PMID- 30181713
TI  - Tumor-associated macrophages derived CCL18 promotes metastasis in squamous cell
      carcinoma of the head and neck.
AB  - Background: Alternatively activated macrophages in tumor microenvironment is
      defined as M2 tumor-associated macrophages (M2 TAMs) that promote cancer
      progression. However, communicative mechanisms between M2 TAMs and cancer cells
      in squamous cell carcinoma of head and neck (SCCHN) remain largely unknown.
      Methods: Quantitative real-time PCR, western blotting, enzyme-linked
      immunosorbent assay and flow cytometry were applied to quantify mRNA and protein
      expression of genes related to M2 TAMs, epithelial-mesenchymal transition (EMT)
      and stemness. Wounding-healing and Transwell invasion assays were performed to
      detect the invasion and migration. Sphere formation assay was used to detect the
      stemness of SCCHN cells. RNA-sequencing and following bioinformatics analysis
      were used to determine the alterations of transcriptome. Results: THP-1 monocytes
      were successfully polarized into M2-like TAMs, which was manifested by increased
      mRNA and protein expression of CCL18, IL-10 and CD206. Conditioned medium from M2
      like TAMs promoted the migration and invasion of SCCHN cells, which was
      accompanied by the occurrence of EMT and enhanced stemness. Importantly, CCL18
      neutralizing antibody partially abrogated these effects that caused by
      conditional medium from M2-like TAMs. In addition, recombinant human CCL18
      (rhCCL18) correspondingly promoted the malignant biological behaviors of SCCHN in
      vitro. Finally, RNA-sequencing analysis identified 331 up-regulated and 363 down
      regulated genes stimulated by rhCCL18, which were statistically enriched in 10
      cancer associated signaling pathways. Conclusion: These findings indicate that
      CCL18 derived from M2-like TAMs promotes metastasis via inducing EMT and cancer
      stemness in SCCHN in vitro.

PMID- 30181714
TI  - MiR-876-5p modulates head and neck squamous cell carcinoma metastasis and
      invasion by targeting vimentin.
AB  - Background: Local or distant metastasis remains the main course of death in head
      and neck squamous cell carcinoma (HNSCC) patients. MicroRNAs (miRNAs) have been
      implicated in metastasis of HNSCC, but the mechanisms of their action are mainly
      undocumented. Through public head and neck cancer miRNA expression datasets, we
      found that miR-876-5p was a novel potential tumor suppressor targeting HNSCC
      metastasis. Methods: Clinical significance and mechanism of miR-876-5P was
      systematically analyzed in HNSCC. Quantitative RT-PCR was used to evaluate miR
      876-5p levels in HNSCC cell lines and in 20 pairs of HNSCC with associated
      regional nodal metastases and HNSCC without metastatic primary tumors. Scratch
      and invasion assays were evaluated to determine the role of miR-876-5p in the
      regulation of HNSCC cell migration and invasion, respectively. Western blotting
      was used to investigate the mechanism by which miR-876-5p suppresses HNSCC cell
      invasion and migration. Luciferase assays were performed to assess miR-876-5p
      binding to the vimentin gene. The animal model was used to support the in vitro
      experimental findings. Results: MiR-876-5p mimics inhibited HNSCC cell migration
      and invasion. Vimentin protein and mRNA levels were decreased in the miR-876-5p
      mimics group but increased in the miR-876-5p inhibitors group, which demonstrated
      that miR-876-5p inhibits vimentin expression in HNSCC cells. By directly
      targeting the vimentin 3'-UTR, we used dual-luciferase reporter assays to verify
      that vimentin is a functional downstream target of miR-876-5p. Importantly,
      increased vimentin expression promoted cell migration and invasion, and co
      transfection with miR-876-5p mimics and vimentin restored cell aggressiveness to
      the original level. Moreover, miR-876-5p overexpression significantly
      downregulated vimentin expression level and inhibited the distal metastasis of
      HNSCC cells in vivo. Conclusions: miR-876-5p, which functions as a tumor
      suppressor in HNSCC, inhibits metastasis by targeting vimentin and provides a
      novel therapeutic target for HNSCC treatment.

PMID- 30181715
TI  - Identification of long non-coding RNA competing interactions and biological
      pathways associated with prognosis in pediatric and adolescent cytogenetically
      normal acute myeloid leukemia.
AB  - Background: LncRNAs can regulate miRNAs and mRNAs by sequestering and binding
      them. Indeed, many researchers have reported lncRNA mediated-competing endogenous
      RNAs (ceRNAs) could regulate the progression of solid tumors. However, the roles
      of ceRNA in acute myeloid leukemia (AML), especially in pediatric and adolescent
      AML, were not completely expounded. Materials and methods: 27 cytogenetically
      normal acute myeloid leukemia (CN-AML) patients under 18 years old with
      corresponding clinical data were selected from the cancer genome atlas (TCGA),
      which was a large sample sequencing database of RNA sequencing. We constructed a
      survival specific ceRNA network, and investigated its associations with patients'
      clinical information by analyzing the data from TCGA. Results: We identified
      survival specific lncRNAs, miRNAs and mRNAs, and constructed a survival specific
      ceRNA network of CN-AML patients and a weighted correlation network. Furthermore,
      we identified 4 biological pathways associated with OS and selected the most
      enriched pathway 'Transcriptional misregulation in cancer' to verify that it
      could accurately predict younger CN-AML patients' prognosis to guide treatment.
      Conclusions: We successfully constructed a survival specific ceRNA network which
      could provide a new approach to lncRNA research in younger CN-AML. Importantly,
      we constructed a weighted correlation network to overcome the difficulty in
      biological interpretation of individual genes.

PMID- 30181716
TI  - Prospective clinical study of capecitabine plus oxaliplatin concurrent
      chemoradiotherapy after radical resection of rectal cancer.
AB  - Background: To investigate the efficacy and safety of concurrent
      chemoradiotherapy with capecitabine or oxaliplatin in locally advanced (T3-4/N +
      M0) rectal cancer. Methods: 56 patients with rectal cancer after radical
      operation were randomly divided into CAPE-OX-CRT group: capecitabine +
      oxaliplatin concurrent chemoradiotherapy (30 cases), CAPE-CRT group: capecitabine
      concurrent chemoradiotherapy (control, 26 cases). Results: The incidence of grade
      1-2 acute toxicity in CAPE-OX-CRT group during concurrent CRT was significantly
      higher than that in control group, the difference was statistically significant
      (P < 0.05). Grade 3 toxicities were not statistically significant between the two
      groups (P > 0.05). No grade 4 toxicity was found in both groups. The incidences
      of interrupted or suspend concurrent chemotherapy in both groups were 19.23% and
      46.67%, respectively, P < 0.05. The incidences of interruption or suspension of
      radiotherapy were 11.54% and 30% respectively (P > 0.05). The completion rate of
      adjuvant chemotherapy in control group was higher than that in CAPE-OX-CRT group,
      but the difference was not statistically significant (P > 0.05). In postoperative
      adjuvant chemotherapy, the incidence of bone marrow suppression in CAPE-OX-CRT
      group was higher than that in control group (P < 0.05), and the incidence of non
      hematologic adverse reactions was similar between the two groups. Conclusion:
      Capecitabine combined oxaliplatin concurrent CRT, and oxaliplatin concurrent CRT
      have a good effect for treatment of patients with locally advanced rectal cancer
      after radical resection of rectal cancer.

PMID- 30181717
TI  - Arteriolar vs. valvular thrombosis: Pick your evil!
AB  - Background: Anticoagulation therapy for mechanical prosthetic valves is limited
      to vitamin K antagonists, unfractionated heparin and low-molecular-weight
      heparin. Other forms of anticoagulation are either contraindicated or have not
      been well studied. Hence, anticoagulation for preexisting mechanical valves is
      controversial if vitamin K antagonists are contraindicated. We present a case
      involving an end-stage-renal disease patient with both mitral and aortic
      mechanical valves who developed warfarin-induced calciphylaxis. Case
      presentation: A 72-year-old male with history of end-stage renal disease, chronic
      atrial fibrillation and rheumatic heart disease status post mitral and aortic
      valve replacements presented with complaints of left thigh erythema with skin
      induration. Despite multiple antibiotic regimens for presumed cellulitis, the
      skin lesions progressed to necrotic ulcers. A biopsy revealed evidence of
      calciphylaxis; a lethal condition typically associated with renal disease. The
      patient was on warfarin for anticoagulation of his mechanical heart valves as
      well as prophylactically for atrial fibrillation. Warfarin contributes to the
      development of calciphylaxis and needed to be exchanged to avoid progression of
      the ulceration. The only other acceptable option for long-term anticoagulation
      was subcutaneous unfractionated heparin but this approach was not taken. The
      patient suffered from further sequelae of calciphylaxis and eventually expired.
      Conclusion: Calciphylaxis is a rare, serious disorder that presents with skin
      ischemia and necrosis mainly in end-stage renal disease patients. The
      pathogenesis and treatment are poorly understood and the prognosis remains grave.
      It is proposed that certain medications, including warfarin, contribute to its
      evolution. The optimal anticoagulation therapy in those with concomitant warfarin
      induced calciphylaxis and mechanical valves is undetermined. Further studies are
      essential to establish new anticoagulation regimens in these devastating
      circumstances.

PMID- 30181718
TI  - A Clinician's Guide to Oral Extended-Release Drug Delivery Systems in Epilepsy.
AB  - Epilepsy is one of the most common chronic neurologic disorders that affects
      individuals of all ages. It is primarily managed with antiepileptic drugs (AEDs),
      with the goal of maintaining complete seizure control combined with minimal or no
      adverse effects. Oral administration is the mainstay of AED delivery for patients
      with chronic epilepsy and consists essentially of immediate-release (IR) and
      modified-release (delayed-release and extended-release [ER]) dosage formulations.
      Extended-release formulations (hydrophilic or hydrophobic matrix systems,
      reservoir systems, and osmotic-release systems) release a drug in a controlled
      manner during an extended period of time following administration. Extended
      release formulations have many advantages compared with IR formulations,
      including simplification of dosing regimens, reduction in pill burden, and
      reduction in the peak-to-trough fluctuations in serum drug concentration that may
      be associated with a decreased risk of adverse effects and of seizures. These
      advantages have the potential to increase adherence to antiepileptic therapy,
      improve the quality of life of patients, and reduce health care costs. This
      article, which is intended as a practical guide for clinicians, reviews the
      properties of the different ER AED formulations currently available and discusses
      the advantages of ER over IR formulations. Subsequently, an explanation of the
      technologic basis of the different oral ER formulations, the critical attributes
      that differentiate ER products, and their individual strengths and weaknesses is
      provided. Specific recommendations to practitioners on treating patients with ER
      formulations are included.

PMID- 30181719
TI  - Pharmacist and Pediatrician Knowledge of Codeine Use in Children.
AB  - OBJECTIVES: In 2011, approximately 1.7 million pediatric patients had a codeine
      containing prescription filled at a US retail pharmacy. Numerous cases involving
      serious adverse effects or fatalities have been reported in children who have
      been prescribed codeine. In 2013, the US Food and Drug Administration added a
      boxed warning to avoid codeine in children after a tonsillectomy. The purpose of
      this study is to determine pharmacists' and pediatricians' knowledge of the boxed
      warning for codeine in children. METHODS: Two separate surveys were administered
      to community pharmacists in Maryland, pediatricians, and pediatric residents at a
      single institution in Maryland. Both surveys consisted of questions regarding
      knowledge of the boxed warning for codeine in children. RESULTS: There was no
      difference in the awareness of the boxed warning between pharmacists (48.9%, n =
      43) and pediatricians (51.3%, n = 41, p = 0.88). More pharmacists knew that
      ultrarapid metabolizers have the risk for increased adverse events from codeine
      (39.5% pharmacists vs. 20% pediatricians, p = 0.01). In addition, 36% of
      pharmacists and 33% of pediatricians noted that it was never appropriate to use
      codeine in a child (p = 0.73). CONCLUSIONS: Only half of pharmacists and
      pediatricians surveyed were aware of the boxed warning for codeine. One third of
      pharmacists and pediatricians in this study would never use codeine in a child.
      Therefore, more education is needed for pharmacists and pediatricians regarding
      the dangers of using codeine in children.

PMID- 30181720
TI  - A Report of an Asthma Pathway Leading to Improved Resource Use.
AB  - OBJECTIVES: Asthma pathways have been shown to improve resource use and decrease
      length of stay (LOS). A tertiary care hospital implemented an asthma pathway in
      May 2015 to standardize inpatient care. We predicted that the pathway would
      increase the use of albuterol metered-dose inhalers (MDIs) and steroids; decrease
      use of albuterol nebulizer, antibiotics, chest radiograph (CXR), and respiratory
      viral panel (RVP); and decrease LOS. METHODS: This retrospective cohort study
      selected patients between the ages of 2 and 18 years who were admitted for asthma
      as a primary diagnosis between May 2014 and May 2016 (1 year preimplementation to
      1 year postimplementation). Patients' complex chronic conditions were excluded.
      We analyzed use of albuterol nebulizer, MDI, and continuous nebulization,
      ipratropium bromide, oral steroids, antibiotics, inhaled steroids, CXR, and RVP.
      We also evaluated LOS and readmission rate. RESULTS: There were 1131 and 925
      patients identified before and after asthma pathway implementation, respectively.
      The percent that received albuterol nebulizer decreased from 14.1% to 6.1% (p <
      0.001). The percent that received albuterol MDI increased from 97.0% to 99.4% (p
      < 0.001). The average number of MDI administrations decreased from 11.6 to 10.4
      (p = 0.004). Continuous albuterol use increased from 52.3% to 59.1% (p = 0.002).
      There was no change in ipratropium bromide, oral steroid, inhaled steroid, or CXR
      use. Antibiotic (p = 0.049) and RVP (p = 0.03) use decreased. The average LOS
      decreased from 1.84 days to 1.71 days (p = 0.02). Readmission rates did not
      change significantly. CONCLUSIONS: The asthma pathway improved inpatient
      albuterol MDI use. The LOS decreased while maintaining readmission rates.

PMID- 30181721
TI  - Therapeutic Drug Monitoring of Vancomycin in Pediatric Patients With
      Extracorporeal Membrane Oxygenation Support.
AB  - OBJECTIVES: Determine pharmacokinetic (PK) parameters and optimal dosage of
      vancomycin for children on extracorporeal membrane oxygenation (ECMO). METHODS:
      Retrospective PK study of vancomycin in pediatric patients on ECMO who received
      IV vancomycin 40 to 60 mg/kg/day every 6 hours. Patients were analyzed according
      to the presence of acute kidney injury (AKI) and requirement of renal replacement
      therapy (RRT). RESULTS: Data from 40 children, with a median age of 2.7 years of
      age (1 month to 14 years) were evaluated. Thirty-two patients (80%) received
      vancomycin. Vancomycin therapeutic drug monitoring was performed in 29 patients.
      The subgroup without AKI or RRT were 15. With initial doses, vancomycin trough
      levels were within therapeutic range in 53% of patients. After dose change, 93%
      of patients achieved therapeutic levels. The adjusted dose was 40 (34-60)
      mg/kg/day every 6 hours. Estimated PK parameters were clearance (CL) 1.67 (1
      1.67) mL/kg/min; volume of distribution (Vd) 0.73 (0.7-0.9) L/kg; and half-life
      (t1/2) 6.2 (4.9-8.06) hours. In the AKI subgroup, 11 patients, the initial median
      dose was 40 (30-45) mg/kg/day every 8 (6-12) hours. Trough concentrations of
      vancomycin were within therapeutic range in 27% of patients. After dose
      modifications, 63% of patients achieved target trough concentration. The final
      adjusted dose was 20 mg/kg/day (15-30) every 12 (12-24) hours. Estimated PK
      parameters were Vd 1.16 (0.68-1.6) L/kg; CL 0.83 (0.38-1) mL/kg/min; and a t1/2
      of 23.6 (16.2-31) hours. CONCLUSIONS: In patients without AKI or RRT, Vd of
      vancomycin was similar and CL was lower compared to pediatric critically ill
      patients without ECMO. Treatment could be started at 40 mg/kg/day every 6 hours.
      In patients with AKI, the use of lower doses should be used.

PMID- 30181722
TI  - Sterility Duration of Preprimed Extracorporeal Membrane Oxygenation Circuits.
AB  - OBJECTIVES: There is a lack of standardization and supporting data regarding the
      duration preassembled and preprimed extracorporeal membrane oxygenation (ECMO)
      circuits are expected to be sterile. Therefore, the purpose of this study was to
      prospectively evaluate whether preassembled and preprimed ECMO circuits could
      maintain sterility for a period up to 65 days. DESIGN: Four ECMO circuits (2
      neonatal/pediatric1/4" and 2 adolescent/adult 3/8 ") were assembled and primed
      under sterile conditions and maintained at room temperature. Culture samples were
      obtained from each circuit and plated within 1 hour. Culture samples were
      obtained on day 0 when assembled and primed then every 5 days up to day 65.
      Samples were plated on several different media including the following: blood
      agar plate: trypticase soy agar with 5% sheep blood, MacConkey agar, and
      thioglycollate broth then incubated at 35 degrees C for 3 days. RESULTS: All
      cultures obtained from the priming solution from of the1/4" and 3/8 " ECMO
      circuits produced no microbial or fungal growth for the 65-day study period.
      CONCLUSION: These pilot data suggest preprimed ECMO circuits may maintain
      sterility for a period up to 65 days. Additional studies evaluating a larger
      number of ECMO circuits are needed to confirm these findings.

PMID- 30181723
TI  - Effect of Exogenous Antithrombin Administration on Anti-Xa Levels in Infants
      Treated With Enoxaparin.
AB  - OBJECTIVES: Determine the effect of exogenous antithrombin III administration on
      low molecular weight heparin anti-Xa levels in the context of enoxaparin dosing
      in infants. METHODS: A retrospective chart review of infants receiving
      concomitant antithrombin III and enoxaparin. The primary objective of this study
      was to determine the median change in anti-Xa level with antithrombin III
      supplementation. Secondary objectives were to analyze the median change in
      antithrombin III levels after administration of exogenous antithrombin III, the
      dosing of antithrombin III, and the dose of enoxaparin throughout therapy. For a
      safety analysis, any bleeding events were recorded. RESULTS: The study included
      17 patients who received a total of 33 doses of antithrombin III. The median
      change in anti-Xa levels in infants receiving exogenous antithrombin III was 0.2
      units/mL (p < 0.001). The median dose of antithrombin III was 50 units/kg and was
      administered when patients were receiving a median enoxaparin dose of 1.71 mg/kg.
      The median increase in antithrombin III levels was 16.5% (p < 0.001).
      CONCLUSIONS: These results demonstrated that administration of exogenous
      antithrombin III to infants who were being treated with enoxaparin results in a
      significant increase in anti-Xa levels. At this time, there is insufficient
      evidence to recommend routine administration of antithrombin III to infants on
      enoxaparin. However, antithrombin III supplementation could be considered a
      potential option for patients who are unable to adequately achieve therapeutic
      anti-Xa levels with enoxaparin alone.

PMID- 30181724
TI  - Development of an Interprofessional Pharmacist-Nurse Navigation Pediatric
      Discharge Program.
AB  - OBJECTIVES: Numerous challenges face clinically complex patients as they
      transition from hospital to home. The purpose of this project was to add pharmacy
      discharge services to an existing nurse-led discharge service (patient navigation
      program) to facilitate the transition of care process for clinically complex
      pediatric patients. METHODS: For select patients referred to the service, a
      pharmacist resolved medication discrepancies, provided discharge counseling, and
      conducted follow-up telephone encounters on days 1, 7, and 14 post discharge.
      Patient demographics, admitting diagnosis, and number of discharge medications
      were recorded. The impact on patient outcomes was measured by the number and type
      of pharmacist interventions identified. Program utilization was measured by the
      number of referrals received, percentage of patients seen by a pharmacist, follow
      up phone call completion rate, and pharmacist time required. Financial benefit
      gained from the program was estimated by translating each pharmaceutical
      intervention into potential cost savings. RESULTS: There were 321 patient
      navigation referrals during the 5 months of pharmacist service. A pharmacist was
      able to provide discharge counseling for 56 discharges (17%). Patients who were
      provided pharmacy services had a median of 8 comorbidities, 10-day length of
      stay, and 4 discharge medications. Pharmacists identified 168 interventions, of
      which 93.5% were accepted or informational in nature. The most frequently
      identified interventions included clarification of drug order, assistance
      obtaining medication, and dose rounding. This program resulted in an estimated
      cost savings of $22,308 in the first 5 months. CONCLUSIONS: A unique partnership
      between nurses and pharmacists facilitated the discharge process for clinically
      complex children.

PMID- 30181725
TI  - Impact of Two Educational Modules on Practitioner Knowledge of Pediatric
      Delirium.
AB  - OBJECTIVES: The purpose of this study was to evaluate the efficacy of education
      modules in preparing staff before the implementation of a pediatric delirium
      screening protocol. METHODS: After consenting participants began phase 1 of the
      study, which covered general information on pediatric delirium. It comprised a 21
      question assessment administered as a pretest followed by an education module and
      then the same 21-question assessment administered as a posttest. After completing
      phase 1, participants proceeded to phase 2, which focused on use of the Cornell
      Assessment of Pediatric Delirium (CAPD) tool. It comprised an education module
      and a 14-question postassessment. Participants completed these phases at their
      convenience via provided instruction documents. Assessments were delivered
      through the online service SurveyMonkey. Education modules were available online
      as invisible YouTube videos. RESULTS: A total of 50 nurses and pharmacists gave
      consent, and 37 of these participants initiated phase 1. All 37 participants
      completed the phase 1 preassessment, averaging a score of 46% (range, 29%-71%). A
      total of 27 participants completed the phase 1 postassessment, with an average
      score of approximately 76% (range, 48%-95%). A total of 20 participants, with no
      prior training on the CAPD, completed the phase 2 postassessment, averaging a
      score of 88% (range, 43%-100%). CONCLUSIONS: Both the pediatric delirium general
      education module and the CAPD use education module resulted in participant
      learning, as evidenced by the assessment score averages.

PMID- 30181726
TI  - Intravenous Ribavirin for Parainfluenza and Respiratory Syncytial Virus in an
      Infant Receiving Extracorporeal Membrane Oxygenation and Continuous Renal
      Replacement Therapy.
AB  - BACKGROUND: Viral bronchiolitis remains a significant cause of hospitalization as
      well as morbidity and mortality during the first year of life, with treatment
      options beyond supportive care being limited. In cases of severe illness,
      ribavirin may offer therapeutic benefit. OBJECTIVE: We report the use of
      intravenous (IV) ribavirin in an infant requiring concomitant venovenous
      extracorporeal membrane oxygenation (VV-ECMO) and continuous venovenous
      hemofiltration (CVVH) for respiratory syncytial virus (RSV) and parainfluenza
      virus (PIV) coinfection. PATIENTS AND METHODS: A 5-week-old male former 33-week
      preterm infant was admitted with respiratory failure and subsequently tested
      positive for RSV and PIV-type 1 infection. Progressive clinical deterioration
      subsequently required the initiation of both VV-ECMO and CVVH. Although the
      patient received combined VV-ECMO and CVVH, IV ribavirin was administered, and
      serial plasma and ultrafiltrate samples were obtained for pharmacokinetic
      analyses after the first dose (collection period 1) and again after an estimated
      5 half-lives (collection period 2). RESULTS: Pharmacokinetics for collection
      period 1 demonstrated a calculated Cmax of 11.99 mg/L, an AUC0-24 of 43.32
      mg.hr/L, ke 0.26 hr-1, t1/2 2.69 hr, Vd 10.04 L (2.92 L/kg, using patient's
      dosing weight 3.43 kg), CLT 43.47 mL/min, and CLCVVH 6.75 mL/min.
      Pharmacokinetics for collection period 2 demonstrated a calculated Cmax of 10.31
      mg/L, AUC0-6 of 52.55 mg. hr/L, ke 0.06 hr-1, t1/2 10.69 hr, Vd 17.5 L (5.1
      L/kg), and CLT 17.44 mL/min. The sieving coefficient during collection period 1
      was 1.17 (range, 1.07-1.37). The percent decline between prefilter and postfilter
      oxygenator was 19.1%. CONCLUSION: Our patient demonstrated therapeutic
      concentrations of ribavirin, despite drug removal via CVVH and the ECMO
      oxygenator. Standard ribavirin dosing used and resultant concentrations achieved
      were associated with viral clearance and clinical improvement.

PMID- 30181728
TI  - Pediatric News.

PMID- 30181727
TI  - Position Paper: Pharmacists and Childhood Vaccines.
AB  - Vaccination rates of children in the United States remain below the target
      coverage levels identified in the Healthy People 2020 objectives. Given the
      success of pharmacists in providing adult vaccinations and the accessibility of
      pharmacists to the public, expanding pharmacists' authority to vaccinate children
      may improve vaccination rates of children, particularly in key disease states.
      This article serves as a Position Statement of the Pediatric Pharmacy Advocacy
      Group (PPAG), who supports the expansion of pharmacists' authority to vaccinate
      children. PPAG also believes that increased use of state vaccination registries
      by pharmacists will help improve communication and documentation of vaccines
      between providers. PPAG also recommends that continued education and maintaining
      current knowledge of vaccines and vaccine schedules are vital for pharmacist
      immunizers. Finally, PPAG believes that pharmacists should be advocates for
      childhood vaccinations.

PMID- 30181729
TI  - The Effect of Photothermal Therapy on Osteosarcoma With Polyacrylic Acid-Coated
      Gold Nanorods.
AB  - Background: Polyacrylic acid (PAA)-coated gold nanorods (GNRs) were prepared in
      this research, and then the structure, stability, temperature increment
      efficiency, and biocompatibility of GNRs@PAA were detected. Methods: It was
      demonstrated that GNRs@PAA coupled with an 808 nm laser had superior efficiency
      of hyperthermia therapy for MG63 human osteosarcoma cell. Results: The mechanism
      of photothermal therapy of GNRs@PAA was explored, and it was proved that damaged
      cell membrane and DNA integration caused cell apoptosis and death, and the cell
      apoptosis rate had been obviously promoted by in vitro photothermal therapy which
      exhibited time-dose dependence. Conclusion: The results demonstrated that the
      GNRs@PAA could be a promising candidate for phototherapeutic applications in
      human osteosarcoma.

PMID- 30181730
TI  - Severe Injuries from Low-height Falls in the Elderly Population.
AB  - Background: Falls from low-height can cause severe injuries in the elderly
      population. This study was conducted to determine characteristics of injuries
      from low-height falls. Methods: We retrospectively review surveillance data on
      injured patients who presented to six emergency departments from January 2011 to
      December 2015. Study subjects were divided into severe group and non-severe group
      based on severity of injury. The general and clinical characteristics were
      compared between the two groups and analyzed factors related with severe
      injuries. Results: Of 1,190 elderly patients, severe group comprised 82 patients
      (7%). The severe group was 2 years younger than the non-severe group. In the
      severe group, 61% was men and 34% in the non-severe group. In the non-severe, the
      injuries more commonly occurred at residential facilities and indoors than those
      in the severe group. Paid work during injury occurrence was 15%, and the more
      patients presented with non-alert consciousness in the severe group. The most
      common regions of major injury were head and neck in the severe group.
      Conclusion: Paid work, non-alert consciousness, and major injury to head and neck
      are relating factors to severe injuries in the elderly population.

PMID- 30181731
TI  - Environmental Tobacco Smoke Exposure at Home and Attributable Problem Behaviors
      in Korean Children and Adolescents for 2012-2014 in a Nationally Representative
      Survey.
AB  - Background: This study aimed to examine the environmental tobacco smoke (ETS)
      exposure at home and associated problem behaviors in Korean children and
      adolescents. Methods: Approximately 2,167 children aged 3-18 years were included
      in the study after excluding 163 active smokers from the Korean Environmental
      Health Survey in Children and Adolescents (2012-2014). ETS data were obtained
      using a questionnaire; problem behaviors were measured using the Child Behavior
      Checklist administered to parents. The relationship between ETS exposure and
      problem behavior was evaluated using a survey regression model adjusted for
      region, age, sex, income, and father's education. The population-attributable
      fraction (PAF%) was calculated based on problem behaviors related to ETS exposure
      at home. Results: The rates of ETS exposure at home were 20%, 28%, and 39% in
      children aged 3-5, 6-11, and 12-18 years, respectively; ETS exposure at home was
      associated with behavioral problems: the exposed group having higher total
      behavioral problem score (95% confidence interval [CI]) than the non-exposed by
      2.46 (0.60-4.32) and 2.74 (0.74-4.74) in children aged 6-11 and 12-18 years,
      respectively, with no significant association in those aged 3-5 years. The PAF%
      (95% CI) of total problem behaviors for ETS exposure at home were 2.68 (-10.11
      17.78), 10.66 (3.25-17.55), and 11.62 (3.03-18.96) in children aged 3-5, 6-11,
      and 12-18 years, respectively. Children with externalizing problems had higher
      PAF% than those with internalizing problems. Conclusion: In Korea, ETS exposure
      at home is associated with problem behaviors in children and adolescents with
      about more than 10% population attributable fraction.

PMID- 30181732
TI  - Characteristics of Korean Patients with Polymyalgia Rheumatica: a Single
      Locomotive Pain Clinic Cohort Study.
AB  - Background: Polymyalgia rheumatica (PMR) is a common systemic inflammatory
      disease of the elderly; however, the clinical characteristics and therapeutic
      response of PMR in Korea have been rarely studied. Methods: We reviewed the
      medical records of 54 Korean patients diagnosed with PMR between January 2009 and
      February 2017 in a locomotive pain clinic of one tertiary referral hospital. We
      analyzed epidemiologic and clinical characteristics, therapeutic responses, and
      prognostic factors for remission-failure at one-year after oral prednisolone
      treatment. Results: In 54 patients with PMR, 32 (59.3%) were female. The average
      age at diagnosis was 65.0 +/- 10.5 years. Duration of symptoms before diagnosis
      was 8.1 +/- 8.6 months. All patients had shoulder pain (54 patients, 100.0%); 49
      patients (90.7%) had hip girdle pain, while 19 patients (35.2%) had peripheral
      joint pain. Four patients (7.4%) were accompanied by the giant cell arteritis
      (GCA). There was no seasonal preference for symptom development. Only 19 patients
      were diagnosed with PMR at initial symptom presentation. At one-year follow-up
      after oral prednisolone treatment, the remission rate was 35.3% (12/34).
      Multivariate analysis showed that history of relapse (odds ratio, 6.81; 95%
      confidence interval, 1.035-44.804) was a significant predictor of remission
      failure. Conclusion: The rate of remission (35.3%) after oral prednisolone
      treatment was similar to previous reports in western countries; and GCA is not a
      rare condition in Korean PMR patients. Misdiagnosis of PMR is common, and
      heightened consideration for PMR is needed in elderly patients who present
      inflammatory features of bilateral shoulder pain.

PMID- 30181733
TI  - Environmental Tobacco Smoke Can Be an Important Risk Factor for Children's
      Behavioral Problems, and Policies to Reduce Exposure Are Urgently Required.

PMID- 30181735
TI  - A New Case of a Rare Combination of Temple Syndrome and Mosaic Trisomy 14 and a
      Literature Review.
AB  - Temple syndrome (TS14) is a relatively recently discovered imprinting disorder
      caused by abnormal expression of genes at the locus 14q32. The underlying cause
      of this syndrome is maternal uniparental disomy of chromosome 14 (UPD(14)mat).
      Trisomy of chromosome 14 is one of the autosomal trisomies; in humans, it is only
      compatible with live birth in mosaic form. Although UPD(14)mat and mosaic trisomy
      14 can arise from the same cellular mechanism, a combination of both has been
      currently reported only in 8 live-born cases. Hereby, we describe a patient in
      whom only UPD(14)mat-associated TS14 was primarily diagnosed. Due to the
      patient's atypical features (for TS14), additional analyses were performed and
      low-percent mosaic trisomy 14 was detected. It can be expected that the described
      combination of 2 etiologically related conditions is actually more prevalent.
      Additional chromosomal and molecular investigations are indicated for every
      patient with UPD(14)mat-associated TS14 with atypical clinical presentation.

PMID- 30181734
TI  - Implementation of Hospital Policy for Healthcare Workers and Patients Exposed to
      Varicella-Zoster Virus.
AB  - Varicella-zoster virus (VZV) causes a highly contagious and generally benign,
      self-limited disease. However, in high-risk populations including
      immunocompromised patients, pregnant women, and neonates, VZV infection can be
      associated with significant morbidity and mortality. Healthcare-associated
      transmission of VZV occurs among healthcare workers (HCWs) and patients by
      airborne transmission or by direct contact with the index case. To minimize the
      risk of transmission in healthcare settings, all VZV-susceptible HCWs should be
      encouraged strongly to be immunized with the varicella vaccine. For post-exposure
      management, active immunization (varicella vaccine), passive immunization
      (varicella-zoster immune globulin) and/or antiviral agents, and isolation could
      be used in specific situations. To prevent the transmission of VZV infection in
      the hospital settings, the development and implementation of hospital policies
      for appropriate infection control is also warranted. This article reviews the
      general information and healthcare-associated transmission of VZV and summarizes
      the recommendations for the pre- and post-exposure management of HCWs and
      patients, in hospital settings.

PMID- 30181736
TI  - Effect of phospholipase A2 inhibitors during infection caused by Leishmania
      (Leishmania) amazonensis.
AB  - Background: Lipid metabolites play an important role in parasite differentiation
      and virulence. Studies have revealed that Leishmania sp. uses prostaglandins to
      evade innate barriers, thus enabling the parasites to survive inside immune
      cells. Despite the role of the enzyme Phospholipase A2 (PLA2) in prostaglandins
      production, few studies have investigated the role of parasite PLA2 during the
      interaction between L. (L.) amazonensis and the host (in vitro and in vivo)
      immune cells. Methods: In the present work, the leishmanicidal effect of PLA2
      inhibitors, methyl arachidonyl fluorophosphonate (MAFP), bromoenol lactone (BEL)
      and aristolochic acid (AA) were investigated in vitro (promastigote and
      intracellular amastigote forms of L. (L.) amazonensis) and during in vivo
      infection using BALB/c mice. Results: The aforementioned inhibitors were
      deleterious to promastigote and amastigote forms of the L. (L.) amazonensis and
      were non-toxic to peritoneal macrophages from BALB/c mice. L. (L.) amazonensis
      infected BALB/c mice treated with the inhibitor BEL presented decreased lesion
      size and skin parasitism; however, BEL treatment induced hepatotoxicity in BALB/c
      mice. Conclusions: Results presented herein suggested that PLA2 inhibitors
      altered L. (L.) amazonensis viability. In spite of liver toxicity, treatment with
      BEL was the most selective compound in vitro, as well in vivo, resulting in lower
      skin parasitism in the infected mice. These findings corroborate the role of PLA2
      in parasite virulence and maintenance in vertebrate hosts, and suggest that
      molecules structurally related to BEL should be considered when planning
      compounds against Leishmania sp.

PMID- 30181738
TI  - Identification, expression and characterization of the recombinant Sol g 4.1
      protein from the venom of the tropical fire ant Solenopsis geminata.
AB  - Background: Fire ant venom is a complex mixture consisting of basic piperidine
      alkaloids, various biologically active peptides and protein components, including
      a variety of major allergenic proteins. Tropical fire ant Solenopsis geminata is
      an important stinging ant species that causes anaphylaxis and serious medical
      problems. Although the biological activities of allergenic venom proteins that
      are unique to ant venom, particularly Solenopsis 2 and 4, are still unknown,
      these proteins are believed to play important roles in mediating the effects of
      the piperidine derivatives in the venom. Methods: In the present study, the cDNA
      cloning, sequencing and three-dimensional structure of Sol g 4.1 venom protein
      are described. The recombinant Sol g 4.1 protein (rSol g 4.1) was produced in E.
      coli, and its possible function as a hydrophobic binding protein was
      characterized by paralyzing crickets using the 50% piperidine dose (PD50).
      Moreover, an antiserum was produced in mice to determine the allergenic
      properties of Sol g 4.1, and the antiserum was capable of binding to Sol g 4.1,
      as determined by Western blotting. Results: The molecular weight of Sol g 4.1
      protein is 16 kDa, as determined by SDS-PAGE. The complete cDNA is 414 bp in
      length and contains a leader sequence of 19 amino acids. The protein consists of
      six cysteines that presumably form three disulfide bonds, based on a predicted
      three-dimensional model, creating the interior hydrophobic pocket and stabilizing
      the structure. The rSol g 4.1 protein was expressed in inclusion bodies, as
      determined by SDS-PAGE. Dialysis techniques were used to refold the recombinant
      protein into the native form. Its secondary structure, which primarily consists
      of alpha-helices, was confirmed by circular dichroism analysis, and the three
      dimensional model was also verified. The results of allergenic analysis performed
      on mice showed that the obtained protein was predicted to be allergenically
      active. Moreover, we report on the possible role of the Sol g 4.1 venom protein,
      which significantly reduced the PD50 from 0.027 to 0.013% in paralyzed crickets
      via synergistic effects after interactions with piperidine alkaloids.
      Conclusions: The primary structure of Sol g 4.1 showed high similarity to that of
      venom proteins in the Solenopsis 2 and 4 family. Those proteins are life
      threatening and produce IgE-mediated anaphylactic reactions in allergic
      individuals. The possible function of this protein is the binding of the interior
      hydrophobic pockets with piperidine alkaloids, as determined by the analysis of
      the structural model and PD50 test.

PMID- 30181737
TI  - Pharmacological characterization of cnidarian extracts from the Caribbean Sea:
      evaluation of anti-snake venom and antitumor properties.
AB  - Background: Cnidarians produce toxins, which are composed of different
      polypeptides that induce pharmacological effects of biotechnological interest,
      such as antitumor, antiophidic and anti-clotting activities. This study aimed to
      evaluate toxicological activities and potential as antitumor and antiophidic
      agents contained in total extracts from five cnidarians: Millepora alcicornis,
      Stichodactyla helianthus, Plexaura homomalla, Bartholomea annulata and
      Condylactis gigantea (total and body wall). Methods: The cnidarian extracts were
      evaluated by electrophoresis and for their phospholipase, proteolytic,
      hemorrhagic, coagulant, fibrinogenolytic, neuromuscular blocking, muscle
      damaging, edema-inducing and cytotoxic activities. Results: All cnidarian
      extracts showed indirect hemolytic activity, but only S. helianthus induced
      direct hemolysis and neurotoxic effect. However, the hydrolysis of NBD-PC, a PLA2
      substrate, was presented only by the C. gigantea (body wall) and S. helianthus.
      The extracts from P. homomalla and S. helianthus induced edema, while only C.
      gigantea and S. helianthus showed intensified myotoxic activity. The proteolytic
      activity upon casein and fibrinogen was presented mainly by B. annulata extract
      and all were unable to induce hemorrhage or fibrinogen coagulation. Cnidarian
      extracts were able to neutralize clotting induced by Bothrops jararacussu snake
      venom, except M. alcicornis. All cnidarian extracts were able to inhibit
      hemorrhagic activity induced by Bothrops moojeni venom. Only the C. gigantea
      (body wall) inhibited thrombin-induced coagulation. All cnidarian extracts showed
      antitumor effect against Jurkat cells, of which C. gigantea (body wall) and S.
      helianthus were the most active; however, only C. gigantea (body wall) and M.
      alcicornis were active against B16F10 cells. Conclusion: The cnidarian extracts
      analyzed showed relevant in vitro inhibitory potential over the activities
      induced by Bothrops venoms; these results may contribute to elucidate the
      possible mechanisms of interaction between cnidarian extracts and snake venoms.

PMID- 30181739
TI  - Sequence analysis of the cDNA encoding for SpCTx: a lethal factor from
      scorpionfish venom (Scorpaena plumieri).
AB  - Background: Lethal factors are multifunctional oligomeric proteins found in the
      venomous apparatus of Scorpaeniformes fish. These toxins elicit not only an array
      of biological responses in vitro but also cardiovascular disorders and strong
      hemolytic, nociceptive and edematogenic activities in vivo. This work describes
      the cloning and molecular identification of two toxin subunits, denominated Sp
      CTx-alpha and Sp-CTx-beta, from scorpionfish venom (Scorpaena plumieri). Methods:
      The primary structures were deduced after cDNA amplification by PCR with primers
      from conserved sequences described in Scorpaeniformes toxins. Following DNA
      sequencing and bioinformatic analysis, the tridimensional structures of both
      subunits were modeled. Results: The translated sequences (702 amino acids, each
      subunit) show homology with other lethal factors, while alignment between Sp-CTx
      alpha and Sp-CTx-beta shows 54% identity. The subunits lack N-terminal signal
      sequences and display masses of approximately 80 kDa each. Both Sp-CTx subunits
      display a B30.2/SPRY domain at the C-terminal region with typically conserved
      motifs as described in these toxins. Secondary structure prediction identified
      six alpha-helices 18 residues long in both alpha and beta subunits, some of them
      amphiphilic with their N-terminal flanked by many basic residues, creating a
      cationic site associated with the cytolytic activity of these toxins.
      Antimicrobial potential sites were identified in Sp-CTx and share some features
      with other peptides presenting variable and broad-spectrum activity. A
      phylogenetic tree built to represent these toxins supports the proximity between
      scorpionfish, lionfish and stonefish. Conclusion: The study identified a putative
      toxin protein whose primary structure is similar to other fish toxins and with
      potential for production of antivenom against scorpionfish envenomation in
      Brazil. As a prelude to structure-function studies, we propose that the toxin is
      structurally related to pore-forming marine toxins.

PMID- 30181740
TI  - MiR-320 regulates cardiomyocyte apoptosis induced by ischemia-reperfusion injury
      by targeting AKIP1.
AB  - Background: MicroRNAs play important roles in regulation of the cardiovascular
      system. The purpose of this study was to investigate microRNA-320 (miR-320)
      expression in myocardial ischemia-reperfusion (I/R) injury and the roles of miR
      320 in cardiomyocyte apoptosis by targeting AKIP1 (A kinase interacting protein
      1). Methods: The level of miR-320 was detected using quantitative real-time
      polymerase chain reaction (qRT-PCR), and cardiomyocyte apoptosis was detected via
      terminal dUTP nick end-labeling assay. Cardiomyocyte apoptosis and the
      mitochondrial membrane potential were evaluated via flow cytometry.
      Bioinformatics tools were used to identify the target gene of miR-320. The
      expression levels of AKIP1 mRNA and protein were detected via qRT-PCR and Western
      blot, respectively. Results: Both the level of miR-320 and the rate of
      cardiomyocyte apoptosis were substantially higher in the I/R group and H9c2 cells
      subjected to H/R than in the corresponding controls. Overexpression of miR-320
      significantly promoted cardiomyocyte apoptosis and increased the loss of the
      mitochondrial membrane potential, whereas downregulation of miR-320 had an
      opposite effect. Luciferase reporter assay showed that miR-320 directly targets
      AKIP1. Moreover, knock down and overexpression of AKIP1 had similar effects on
      the H9c2 cells subjected to H/R. Conclusions: miR-320 plays an important role in
      regulating cardiomyocyte apoptosis induced by I/R injury by targeting AKIP1 and
      inducing the mitochondrial apoptotic pathway.

PMID- 30181741
TI  - Association of a disintegrin and metalloproteinase with a thrombospondin type 1
      motif member 13 polymorphisms with severity of coronary stenosis in type 2
      diabetes mellitus.
AB  - Background: The imbalance of von Willebrand factor (vWF) and a disintegrin and
      metalloproteinase with a thrombospondin type 1 motif member 13 (ADAMTS13) has
      been associated with atherosclerosis progression. A high level of vWF which
      regulates thrombus formation is associated with diabetes mellitus (DM), and some
      ADAMTS13 and vWF polymorphisms have effects on their levels. Therefore, this
      study aimed to evaluate the associations of ADAMTS13 and vWF polymorphisms and
      their levels with DM and severity of coronary stenosis. Materials and Methods:
      Eighty-seven DM and 84 control individuals were recruited. vWF and ADAMTS13
      activities as well as vWF antigen were measured by collagen-binding assay (CBA),
      residual-CBA, and in-house enzyme-linked immunosorbent assay, respectively.
      ADAMTS13 and vWF polymorphisms were determined by polymerase chain reaction
      restriction fragment length polymorphism. Results: The E and G alleles and AA
      genotype of ADAMTS13 Q448E, rs2073932, and rs652600, respectively, were
      independently associated with DM (odds ratio [OR] [95% confidence interval (CI)]
      = 2.5 [1.1, 5.6], 2.3 [1.0, 5.2], and 4.7 [1.2, 18.6], respectively). Moreover, E
      allele and AA genotype of Q448E and rs652600 were also significantly associated
      with multi-vessel disease (OR [95% CI] = 2.2 [1.0, 4.8] and 3.2 [1.0, 10.0],
      respectively), while the E and G allele of Q448E and rs2073932 were associated
      with high Gensini score (OR [95% CI] = 2.3 [1.1, 4.9] and 2.3 [1.1, 5.1],
      respectively). Conclusion: Association of ADAMTS13 polymorphisms with DM, number
      of vessel stenosis, and Gensini score may indicate the possible contribution of
      ADAMTS13 polymorphisms to atherosclerosis progression and severity of coronary
      stenosis in DM.

PMID- 30181743
TI  - Clinical assessment of patients with acromegaly.
AB  - Background: In this study, we aimed to retrospectively evaluate treatment
      outcomes and treatment methods in acromegaly patients. Materials and Methods: The
      study included 65 acromegaly patients followed in Sakarya University Faculty of
      Medicine Department of Endocrinology in Turkey between 2004 and 2013. Clinical,
      biochemical, and radiological data were obtained retrospectively from the medical
      files of the patients. All cases have been discussed in the endocrinology and
      pituitary surgery council, and a multidisciplinary treatment approach had been
      chosen in management. Results: Sixty-five patients were included in the study. Of
      the patients, 57% were female. Mean age was 45.3 +/- 9.2 years old. Of the cases,
      12.3% were microadenomas (n = 8, tumor diameter <10 mm) and 87.6% were
      macroadenomas (n = 57, tumor diameter >=10 mm). In our study, 70% remission was
      achieved with the first operation and medical treatment. Patients with invasive
      acromegaly without remission after the first operation underwent reoperation,
      medical treatment, and conventional or stereotactic radiotherapy and achieved 45%
      remission rate. Conclusion: Pituitary surgery is the first treatment option for
      acromegaly. In patients who could not be remissioned after the first operation,
      remission can be achieved by combined therapy consist of reoperation, medical
      treatment, and conventional or stereotactic radiotherapy.

PMID- 30181742
TI  - The complex effects of adipokines in the patients with kidney disease.
AB  - Kidney diseases are categorized as the highest prevalent ones with worldwide
      noticeable incidence. They cause accelerated cardiovascular diseases and
      noticeable mortalities. Adipose tissue and its messengers, adipokines, are
      reported to have the highest relationship with end-stage renal diseases or
      chronic kidney diseases. Over recent years, with shifting of scientists' mindset
      from a simple overview of adipose tissue as a fat store to the complex paradigm
      of this issue as a multipotential secretory organ, the importance of studies on
      this tissue has emerged.

PMID- 30181744
TI  - The relationship between L-leucine-7-amido-4-methyl coumarin 1 gene polymorphism
      and susceptibility to the chronic hepatitis B virus infection in an Iranian
      population.
AB  - Background: Lamnin has important effects on human immunity system. The current
      study aimed to assess the role of L-leucine-7-amido-4-methyl coumarin 1 gene
      polymorphisms on hepatitis B virus (HBV) susceptibility. Materials and Methods:
      The rs20558, rs20563, rs10911193, rs10911251, and rs1413390 polymorphisms were
      analyzed using polymerase chain reaction (PCR) and PCR-reaction-restriction
      fragment-length polymorphism and amplification-refractory mutation system-PCR
      using three different groups including chronic HBV-infected patients, HBV
      patients who were resolved their infection spontaneously and healthy volunteers.
      Laminin concentrations were also measured in the blood of these individuals.
      Results: People with rs20558C, rs20563G, and rs10911193T alleles have an
      increased risk of HBV infection. Moreover, we found that CGTAT haplotype was more
      frequent in chronically infected people who could affect the mechanism of
      disease. Furthermore, there was a significant relationship between laminin
      concentration and rs20558, rs20563, and rs10911193 genotypes in patients.
      Conclusion: According to the statistical analysis, rs20558, rs20563, rs10911193
      polymorphisms probably, related to the chronic HBV infection. In addition, no
      association of the rs10911251, rs1413390 single nucleotide polymorphisms with the
      disease was found.

PMID- 30181746
TI  - Can routine peripheral blood counts like neutrophil-to-lymphocyte ratio be
      beneficial in prediagnosis of testicular cancer and its stages?
AB  - Background: The purpose of this study was to assess the diagnostic role of
      preoperative hematological parameters, especially neutrophil-to-lymphocyte ratio
      (NLR), platelet-to-lymphocyte ratio (PLR), and mean platelet volume (MPV) in germ
      cell testicular malignancies and their prediagnostic role in staging of
      testicular cancer. Materials and Methods: In this cross-sectional retrospective
      study, we analyzed 39 patients who underwent radical orchiectomy due to a
      testicular cancer (Group 1) and 82 patients on whom varicocelectomy procedure was
      performed as control group (Group 2) between January 2006 and January 2016 in our
      clinic. Evaluation of the preoperative hematological parameters in both groups
      and also the subgroups in malignancy group according to histopathological stages
      was conducted in this study. Results: When the hematological parameters were
      compared, a statistically significant difference was found between the two groups
      in terms of neutrophil counts, NLR, PLR, and MPV. NLR and PLR were significantly
      higher and MPV was significantly lower in testicular cancer group compared to the
      control group. NLR was 3.1 +/- 1.4 and 2.0 +/- 1.5, PLR was 141.3 +/- 53.2 and
      115.7 +/- 44.8, and MPV was 8.9 +/- 1.0 and 9.3 +/- 1.1 for testicular cancer and
      control groups, respectively (P < 0.05). Furthermore, differences were observed
      between only mean corpuscular volume, mean corpuscular hemoglobin, and MPV (P <
      0.05) in different stages of malignancy. Conclusion: In accordance with these
      findings, NLR, PLR, and MPV may be helpful for prediagnosis of testicular
      malignancies. Hematological parameters will become important in the preoperative
      assessment for those patients.

PMID- 30181745
TI  - Mycobacterium tuberculosis and lipids: Insights into molecular mechanisms from
      persistence to virulence.
AB  - Mycobacterium tuberculosis is a causative agent of tuberculosis that causes
      deaths across the world. The pathogen apart from causing disease manifestations
      can also enter into a phase of latency to re-emerge later. Among the various
      factors associated with the virulence of pathogen, the lipids composing the cell
      wall of the bacillus have drawn much interest among. The unique composition of
      the cell wall composed of mycolic acid, glycolipids such as diacyltrehaloses,
      polyacyltrehalose, lipomannan, lipoarabinomannan (LAM), mannose-capped-LAM,
      sulfolipids, and trehalose-6,6'-dimycolate, all have been implicated in providing
      the pathogen an advantage in the host. The pathogen also alters its metabolism of
      fatty acids to survive the conditions in the host that is reflected in an altered
      cell wall composition in terms of lipids. In addition, the lipid profile of the
      cell wall has been shown to modulate the immune responses launched by the host,
      especially in the suppression, or production of inflammatory factors, cytokines,
      and phagocytic cells, such as dendritic cells and macrophages. Apart from M.
      tuberculosis, the paper also briefly looks at the role of Mycobacterium bovis and
      its role in tuberculosis in humans along with its lipid profile of its cell wall.
      This review aims to summarize the various lipids of the cell wall of M.
      tuberculosis along with their roles in enabling the pathogen to maintain its
      virulence to infect further humans and its persistence inside the host.

PMID- 30181747
TI  - Comparison of support vector machine based on genetic algorithm with logistic
      regression to diagnose obstructive sleep apnea.
AB  - Background: Diagnosing of obstructive sleep apnea (OSA) is an important subject
      in medicine. This study aimed to compare the performance of two data mining
      techniques, support vector machine (SVM), and logistic regression (LR), in
      diagnosing OSA. The best-fit model was used as a substitute for polysomnography
      (PSG), which is the gold standard for diagnosing this disease. Materials and
      Methods: A total of 250 patients with sleep problems complaints and whose disease
      had been diagnosed by PSG and referred to the Sleep Disorders Research Center of
      Farabi Hospital, Kermanshah, between 2012 and 2015 were recruited in this study.
      To fit the best LR model, a model was first fitted with all variables and then
      compared with a model made from the significant variables using Akaike's
      information criterion (AIC). The SVM model and radial basis function (RBF)
      kernel, whose parameters had been optimized by genetic algorithm, were used to
      diagnose OSA. Results: Based on AIC, the best LR model obtained from this study
      was a model fitted with all variables. The performance of final LR model was
      compared with SVM model, revealing the accuracy 0.797 versus 0.729, sensitivity
      0.714 versus 0.777, and specificity 0.847 vs. 0.702, respectively. Conclusion:
      Both models were found to have an appropriate performance. However, considering
      accuracy as an important criterion for comparing the performance of models in
      this domain, it can be argued that SVM could have a better efficiency than LR in
      diagnosing OSA in patients.

PMID- 30181748
TI  - A rare complication of nasogastric tube insertion.

PMID- 30181749
TI  - The association between index of nutritional quality and ulcerative colitis: A
      case-control study.
AB  - Background: Ulcerative colitis (UC) is a chronic inflammatory bowel disease.
      Recent studies have shown that dietary factors play an important role in the
      development of UC. Index of Nutritional Quality (INQ) is a suitable method that
      analyzes quantitatively and qualitatively single foods, meals, and diets. The aim
      of this study was to determine the association between INQ and UC. Materials and
      Methods: Overall, 62 newly diagnosed cases with UC and 124 healthy age- and sex
      matched controls were studied in a referral hospital in Tabriz, Iran. INQ scores
      were calculated based on information on the usual diet that was measured by a
      valid and reliable Food Frequency Questionnaire consisting of 168 food items.
      Logistic regression analysis adjusting for age, gender, body mass index,
      education, smoking, Helicobacter pylori, family history of UC, appendectomy,
      alcohol, and total energy intake was used to estimate multivariable odds ratios
      (ORs). Results: After controlling for several covariates, we found inverse
      associations between UC risk and INQs of Vitamin C (OR = 0.34 [0.16-0.73]) and
      folate (OR = 0.11 [0.01-0.99]). In crude model of analysis, cases had a higher
      intake of total energy, protein, carbohydrate, total fat, saturated fatty acid,
      monounsaturated fatty acid, polyunsaturated fatty acid, niacin, Vitamin B6,
      Vitamin B12, magnesium, zinc, copper, selenium, and iron compared to controls,
      whereas controls had higher intakes of Vitamin C, Vitamin D, folate, and biotin
      compared to cases. Conclusion: Our results indicate that enough consumption of
      Vitamin C and folate was associated with lower risk of UC.

PMID- 30181750
TI  - Chemotherapy-related infectious complications in patients with Hematologic
      malignancies.
AB  - Background: The objective of the present study was to determine the association
      between chemotherapy and infectious complications in patients diagnosed with
      Hematologic malignancies (HMs). Materials and Methods: The study included 463
      patients diagnosed with HMs multiple myeloma (MM), Hodgkin's lymphoma (HL), non
      HL (NHL), acute myeloid leukemia (AML), acute lymphocytic leukemia, chronic
      lymphocytic leukemia, and chronic myeloid leukemia, between January 2014 and June
      2015. The patients were followed for 1 year after inclusion, to record the
      infectious complications. The collected data included age, sex, type of
      chemotherapy regimen, and several blood tests at admission. All patients received
      prophylactic treatment with antibiotics and antifungal agents. For each
      infection, we recorded the microbiological diagnosis and the day of occurrence
      since HMs diagnosis. Results: In patients with MM, we found that the treatment
      with growth factors (hazard ratio [HR] 2.2; confidence interval [CI] 95%: 1-4.6;
      P = 0.03) was associated with a higher chance of infectious complications. In
      patients with non-Hodgkin lymhoma (LNH), the following drugs were associated with
      a higher infectious incidence: cytarabine (HR: 2.3; CI 95%: 1-5; P = 0.03),
      methotrexate (HR: 2.1; CI 95%: 1.8-4; P = 0.01), dexamethasone (HR: 1.7; CI 95%:
      0.9-3; P = 0.06), growth factors (HR: 1.7; CI 95%: 0.9-3.2; P = 0.001), and
      etoposide (HR: 2.5; CI 95%: 1.5-4.2; P = 0.002). Cytarabine (induction) (HR: 2;
      CI 95%: 1.1-3.7; P = 0.01), cytarabine (consolidation) (HR: 2.1; CI 95%: 1.3-3.5;
      P = 0.01), and growth factors (HR: 2.1; CI 95%: 1.3-3.5; P = 0.002) were often on
      the therapeutic plan of patients with AML, which developed infections.
      Conclusion: Regarding the chemotherapy regimen, the highest incidences of
      infectious complications were observed for growth factors and cytarabine.

PMID- 30181751
TI  - Serum-based microRNA biomarkers for major depression: MiR-16, miR-135a, and miR
      1202.
AB  - Background: Depression is a common medical condition with a high prevalence
      leading to emotional abnormality. Despite some drawbacks, depression currently
      diagnosed using a combination of patient interviews and self-report
      questionnaires. Recently, there is emerging emphasis to establish biomarkers to
      diagnosis and clinical management of depression. This case-control study was
      designed to develop microRNA (miRNA)-based serum biomarker for depression.
      Materials and Methods: In this study, 39 patients with depression and 36 healthy
      controls were enrolled. Serum miRNAs gene expression was measured using real-time
      polymerase chain reaction (PCR) analysis; finally, the data represent as the 2
      DeltaCt followed by further statistical analysis. Results: The serum level of miR
      16 was significantly (P < 0.001) down-regulated (mean: 0.9123 and standard
      deviation [SD]: 0.06) in compared to normal individuals (mean: 1.6848 and SD:
      0.09). The concentration of miR-135a was also catastrophically decreased (P <
      0.001) in the patients (mean: 1.160 and SD: 0.07) in compared to control (mean:
      1.819 and SD: 0.09). The relative miR-1202 expression levels were significantly
      lower (P < 0.001) in the patients (mean: 0.1755 and SD: 0.01) than in the healthy
      individuals (mean: 0.2939 and SD: 0.01). The receiver operating characteristic
      curve analysis indicated the obvious separation between patient and healthy
      control, with an AUC of 0.75 (95% confidence interval [CI] = 0.642-0.858, P <
      0.001), 0.72 (95% CI = 0.607-0.834, P < 0.001), and 0.74 (95% CI = 0.630-0.861, P
      < 0.001) for miR-16, miR-135a, and miR-1202, respectively. The data suggest that
      these miRNAs have a potential to be used as a biomarker of depression with
      sensitivity 77.8% and specificity of 61.5% for miR-16, 94.4% and 41.0% for miR
      135a as well as 86.1% and 61.5% for miR-1202, respectively (P < 0.001).
      Conclusion: Our findings showed that these miRNA can be used as a biomarker of
      depression diagnosis. MiR-135a and miR-1202 exhibited better sensitivity and
      specificity, respectively.

PMID- 30181752
TI  - Rare histological subtype of pulmonary artery intimal sarcoma diagnosed by
      multidisciplinary approach.
AB  - Pulmonary artery intimal sarcoma (PAS) is a rare mesenchymal tumor mostly
      diagnosed in middle-aged women. In a 63-year-old female, the radiological
      findings showed cavitation in the left upper lobe of the lung and infiltrative
      tumor mass around the left pulmonary artery. PAS consisted of small, round tumor
      cells with about 80% of mitotic activity and with myxoid background and specific
      immunoprofile and diagnosed as undifferentiated sarcoma with round cell features
      type. The final diagnosis of PAS was established according to the
      pathohistological, chest computed tomography scan, and surgery finding.

PMID- 30181753
TI  - Serum levels of serotonin as a biomarker of newly diagnosed fibromyalgia in
      women: Its relation to the platelet indices.
AB  - Background: This study aimed to assess the serum serotonin levels in the newly
      diagnosed fibromyalgia (FM) and to relate these levels to the presenting signs
      and symptoms. Materials and Methods: This case-control study included 35 healthy
      women (Group I) served as controls and 130 women with newly diagnosed FM (Group
      II). The diagnosis of FM was confirmed by the diagnostic criteria of the American
      College of Rheumatology-10. The assessment of pain using a revised fibromyalgia
      impact questionnaire and tender points scoring, blood platelet indices, and serum
      serotonin levels were determined. Results: Group II patients had significantly (P
      < 0.001) higher values of mean platelet volume (MPV) (10.60 +/- 1.57fL) and
      platelet width distribution (16.25 +/- 1.45%) than the corresponding values in
      Group I (8.73 +/- 0.81fL and 15.0 +/- 1.15%). Significant low-serum serotonin
      levels observed in Group II patients compared with Group I healthy individuals
      (187.3 +/- 50.3 ng/ml vs. 219.5 +/- 78.3 ng/ml, P = 0.026). Multiple linear
      regression analysis showed the nonsignificant correlations between serum
      serotonin levels and platelet indices in Group II patients. Conclusion: Newly
      diagnosed FM women have significantly low-serum serotonin levels, which does not
      correlate with a significant increment of the platelet activity expressed as
      increase MPV and platelet width distribution percentage. Therefore, this study
      highlighted that the correction of serum serotonin level by medicines could help
      the patients.

PMID- 30181754
TI  - Pulse wave analyzed cardiovascular parameters in young first degree relatives of
      hypertensives.
AB  - Background: First-degree relatives (FDRs) of hypertensive (HT) are predisposed to
      hypertension (HTN) which accelerates cardiovascular aging. Same can be studied
      noninvasively by pulse wave analysis (PWA), encompassing central hemodynamics
      such as central blood pressure (cBP), cardiac output, and stroke work (SW) and
      vascular stiffness parameters such as pulse wave velocity (PWV) and augmentation
      index at HR 75 (AIx@75). We studied PWA-derived cardiovascular parameters in FDRs
      of HT compared to controls. Materials and Methods: We conducted a case-control
      study in 119 FDRs of HT and 119 matched controls. Oscillometric PWA was performed
      by Mobil-o-Graph (IEM, Germany) and cardiovascular parameters were compared. P <
      0.05 was considered statistically significant. Results: Groups were comparable
      with gender, age, height, weight, body mass index, and physical activity. FDRs of
      HT had significantly higher brachial and cBPs, SW (101.41 +/- 25.44 vs. 88.31 +/-
      20.25, P = 0.001), rate pressure product-119.40 +/- 25.34 vs. 108.34 +/- 18.17, P
      < 0.0001), PWV (5.22 +/- 0.46, P < 0.0001), and AIx@75 (31.48 +/- 9.01 vs. 27.95
      +/- 9.4, P = 0.002) than control. Dependent study variables correlated with
      brachial blood pressure more in magnitude and significance level than age or
      anthropometric variables. PWA results of FDR with maternal inheritance did not
      differ significantly from those with paternal inheritance. Conclusion: PWA
      reveals early cardiovascular aging in young FDRs of HTs. It clues to future
      cardiovascular disease including HTN itself, need for primary prevention, and
      further study for consolidation of these results.

PMID- 30181755
TI  - Comparison of the effects of pegylated granulocyte-colony stimulating factor and
      granulocyte-colony stimulating factor on cytopenia induced by dose-dense
      chemotherapy in breast cancer patients.
AB  - Background: Myelosuppression is one of the frequent side effects of chemotherapy
      in breast cancer patients. Granulocyte-colony stimulating factor (G-CSF) and
      pegylated G-CSF are used for the prevention of neutropenia after chemotherapy.
      Pegylated G-CSF has longer half-life of action and can be used as a single dose
      in comparison to G-CSF. The aim of this study is to compare the grade of
      cytopenia and side effects between G-CSF and biosimilar pegylated G-CSF in breast
      cancer patients treated with dose-dense chemotherapy. Materials and Methods: In
      the cross-over clinical trial study, 24 women with breast cancer were randomly
      divided into two groups and treated with dose-dense chemotherapy. The first group
      was treated with single dose of 6 mg biosimilar pegylated G-CSF 24 h after the
      first course of chemotherapy and the second course was followed by 300 MUg daily
      injection of G-CSF for 6 days. The chemotherapy regimen was combination of
      doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2. The second group was treated
      with G-CSF after the first course and pegylated G-CSF after the second course.
      Cell blood count (CBC) and side effects were evaluated 1 and 2 weeks after both
      courses of chemotherapy. Results: In this study, no significant carryover effect
      and treatment effect about the CBC parameters was found between pegylated G-CSF
      and G-CSF. Patients who were treated with biosimilar pegylated G-CSF had
      significantly higher side effects such as bone pain (P = 0.09) and
      gastrointestinal effects (P = 0.005) in comparison to G-CSF. Conclusion: G-CSF
      and biosimilar pegylated G-CSF are effective in reducing cytopenia in breast
      cancer patients treated with dose-dense chemotherapy, but side effects induced by
      pegylated G-CSF (Pegagen) are higher.

PMID- 30181756
TI  - Unmet health-care needs in people with disabilities: An evidence to make reforms
      in health insurance programs in Iran.

PMID- 30181757
TI  - Vitamin D, the gut microbiome and inflammatory bowel disease.
AB  - Vitamin D has an important role in bone metabolism but recently has been
      recognized as an immunoregulator, and this has led to investigations on the
      effect of Vitamin D supplementation in various autoimmune diseases and its anti
      inflammatory effects. There is some evidence that Vitamin D can regulate
      gastrointestinal inflammation. In addition, previous studies have shown that
      Vitamin D can affect the gut microbiome. The aim of this review is to evaluate
      the effect of Vitamin D on inflammatory processes, especially its relation to the
      inflammatory bowel disease (IBD) and gut microbiome. There is some evidence that
      Vitamin D can regulate gastrointestinal inflammation, with epidemiological
      studies showing that individuals with higher serum Vitamin D have a lower
      incidence of IBD, particularly Crohn's disease. Vitamin D changes transcription
      of cathelicidin and DEFB4 (defensin, beta 4) that can affect the gut microbiome.
      Several cell types of the immune system express Vitamin D receptor, and hence the
      use of Vitamin D in immune regulation has some potential. Furthermore, Vitamin D
      deficiency leads to dysbiosis of gut microbiome and reported to cause severe
      colitis. Vitamin D supplementation is low cost and available and can be a
      therapeutic option.

PMID- 30181758
TI  - How may Doppler indices help in the differentiation of obstructive from
      nonobstructive hydronephrosis?
AB  - Background: We assess the potency of different Doppler indices in the
      differentiation of obstructive and nonobstructive hydronephrosis. Materials and
      Methods: In this study, infants and children who were referred for the evaluation
      of unilateral hydronephrosis were enrolled. Ultrasonography for the assessment of
      the degree of hydronephrosis and a voiding cystourethrogram for the exclusion of
      vesicoureteral reflux was performed. Then, Doppler ultrasonography was done for
      both kidneys of each patient using four classic Doppler indices as well as the
      difference (delta) of each index between to kidneys. Diuretic renography with 99
      mTc-ethylene dicysteine (99 mTc-EC) was performed for each patient. Results:
      Thirty-nine patients met the inclusion criteria. After diuretic renography, 29
      (74.35%) patients had shown a nonobstructive pattern, and ten (25.65%) patients
      had a partial (intermediate) or complete obstruction. Using receiver operating
      characteristic (ROC) curve, none of the classic indices of Doppler duplex (i.e.,
      resistive index [RI], resistance index, end diastolic velocity, and peak systolic
      velocity) had the ability to make a difference between obstructive and
      nonobstructive hydronephrosis. However, by calculating the difference (delta) of
      these indices between two kidneys of each patient, delta RI could differentiate
      the nonobstructive condition, significantly (P = 0.006). A cutoff value of 0.055
      has 60% sensitivity and 82.8% specificity. The area under the ROC curve for delta
      RI is 0.795 (standard error: 0.086, 95% confidence interval [CI]: 0.626, 0.964).
      Furthermore, RI ratio between two kidneys of each patient could differentiate the
      nonobstructive condition, significantly (P = 0.012). A cutoff point of 1.075 has
      70% sensitivity and 82.8% specificity. The area under the ROC curve for RI ratio
      was 0.769 (standard error: 0.104, 95% CI: 0.565, 0.973). Conclusion: This study
      shows that RI ratio and delta RI with a high specificity could differentiate
      nonobstructive hydronephrosis and therefore it is a promising way to use
      especially in the follow-up of children with hydronephrosis.

PMID- 30181759
TI  - Attenuation of lipid peroxidation and atherogenic factors in diabetic patients
      treated with gliclazide and metformin.
AB  - Background: Diabetes is associated with oxidative stress and considered as a
      major risk factor for cardiac disease. We attempted to investigate the role of
      oral antidiabetic (OAD) agents gliclazide and metformin in lowering the lipid
      peroxidation and managing the risk for cardiovascular (CV) complications in
      diabetic patients in comparison with nondiabetic healthy individuals. Materials
      and Methods: This cross-sectional study was comprised of 150 individuals grouped
      in three, namely, Group A (n = 60) healthy volunteers, Group B (n = 30) newly
      diagnosed diabetes, and Group C (n = 60) diabetes treated with OAD. Serum
      malondialdehyde (MDA), nitric oxide (NO), and Vitamin C were assessed for
      studying lipid peroxidation status, whereas serum triglyceride (TG) and total
      cholesterol were monitored as predictors for CV risk. Results: We found
      significantly higher concentrations of MDA and NO levels (P < 0.001) in both
      groups of patients (Group B and C) in comparison to control group (Group A).
      Regarding antioxidants, significantly lower concentrations of Vitamin C (P =
      0.046) were found in Group B and C compared to Group A. Moreover, there was
      significant difference exhibited in concentration level of MDA (P = 0.001) and NO
      (P = 0.015) between Group B and C, whereas difference of Vitamin C (P = 0.147)
      was not statistically significant. Conclusion: Our data confirmed that treatment
      with gliclazide and metformin significantly reduced the lipid peroxidation
      accompanied with attenuated levels of serum TGs and cholesterol and suggested
      that oral hypoglycemic agents have great impact to reduce the oxidative stress
      and increase the antioxidant status in diabetes.

PMID- 30181760
TI  - The role of anti-vascular endothelial growth factor (anti-VEGF) in the management
      of proliferative diabetic retinopathy.
AB  - Diabetes is a major cause of visual impairment among working-age adults in the
      United States. The proliferative form of diabetic retinopathy is associated with
      severe vision loss (acuity <5/200). The standard treatment in proliferative
      diabetic retinopathy (PDR) is panretinal photocoagulation (PRP), which is
      effective but has established side effects such as peripheral visual-field
      constraints. Vascular endothelial growth factor (VEGF) is thought to drive the
      process of vascular proliferation. Drugs targeting VEGF (anti-VEGF) have been
      studied extensively in diabetic macular edema (DME), and results have shown that
      diabetic retinopathy regresses with anti-VEGF treatment. Recent studies show that
      anti-VEGF is not inferior to PRP for PDR while treatment is maintained, though
      recurrence rate when anti-VEGF treatment is stopped is unclear. In vitreous
      hemorrhage where PRP cannot be performed, use of anti-VEGF medications can treat
      underlying PDR and delay or reduce need for vitrectomy. Limitations of anti-VEGF
      treatment, however, require careful patient selection and monitoring. This review
      discusses recent clinical trials and guidelines for anti-VEGF use in PDR.

PMID- 30181761
TI  - Timing matters: traffic noise accelerates telomere loss rate differently across
      developmental stages.
AB  - Background: Noise pollution is one of the leading environmental health risks for
      humans, linked to a myriad of stress-related health problems. Yet little is known
      about the long-term effects of noise on the health and fitness of wildlife. We
      experimentally investigated the direct and cross-generational effects of traffic
      noise on telomeres; a measure of cellular ageing that is predictive of disease
      and longevity in humans and other organisms. We exposed zebra finches (Taenopygia
      guttata) to three different treatment groups: 1) parents were exposed to traffic
      noise before and during breeding, together with their nestling young, 2) fledged
      juveniles but not their parents were exposed to traffic noise, and 3) control
      group birds were never exposed to traffic noise. Results: Although there was no
      significant effect of traffic noise exposure at early (pre-fledging) stages of
      offspring telomere length or loss rate, traffic noise exposure accelerated
      telomere loss in older (post-fledging) juveniles. Conclusions: The age-dependent
      differences found in this study in telomere loss could occur if parents buffer
      younger offspring against the detrimental effects of noise exposure and/or if
      younger offspring are less sensitive to noise exposure. Telomere length during
      early life has been shown to be positively related to lifespan and the observed
      noise-induced increase of telomere attrition rate could reduce the fitness of the
      affected birds and potentially alter the population dynamics of birds in noise
      polluted areas. Our data highlight the need to consider the developmental stage
      of an organism to better understand the ecological consequences of anthropogenic
      change.

PMID- 30181762
TI  - PPARgamma/Pgc-1alpha-Fndc5 pathway up-regulation in gastrocnemius and heart
      muscle of exercised, branched chain amino acid diet fed mice.
AB  - Background: Previous studies have revealed the inductive effect of branched-chain
      amino acids (BCAAs) catabolism on fatty acid oxidation and metabolism, especially
      in muscle cells. In the present investigation, we have attempted to address
      whether a combination of BCAAs supplement consumption with aerobic exercise could
      elaborate the expression of PPARgamma, Pgc-1alpha and Fndc5 genes in
      gastrocnemius muscle and heart tissue of male C57BL/6 mice. Methods: Thirty-six
      young male mice with an average weight of 18 +/- 2 g were selected. Mice were
      randomly assigned to 6 groups: 20 mg/mL of BCAAs consumption with simultaneous
      exercise-training, 60 mg/mL of BCAAs consumption with simultaneous exercise
      training, exercise-trained with no BCAAs consumption group, 20 mg/mL BCAAs
      without exercise-training, 60 mg/mL BCAAs without exercise-training, and
      untrained mice without BCAAs consumption. Results: The findings showed a
      combination of 20 mg/mL BCAAs with aerobic exercise significantly increased
      Fndc5, PPARgamma, Pgc-1alpha gene expression in skeletal muscles although,
      circulating Irisin levels remained unchanged (p < 0.05). Interestingly, plasma
      urea and lactate levels were significantly increased in 60 mg/mL BCAAs
      administrated mice which performed exercised (p < 0.05). Two-way analysis of
      variance (ANOVA) was used to examine significant difference between groups and
      sedentary group. Conclusions: Results showed inductive effect of 20 mg/mL BCAAs
      on expression levels of Fndc5, PPARgamma, Pgc-1alpha in gastrocnemius muscle
      similar with counterparts in heart tissue. Of note, higher serum irisin levels
      were detected after 20 mg/mL BCAAs supplementation coincided with the exercise.
      Graphical abstract: An Overview on supplemantaion of branched chain amoinoacids
      on metablism of skeletal muscle and heart.

PMID- 30181763
TI  - Determinants of exclusive breastfeeding in rural South India.
AB  - Background: While breastfeeding rates have improved globally, disparities in
      breastfeeding practices persist particularly in rural and low resource settings.
      In India, only 56% of Indian mothers practice exclusive breastfeeding (EBF) for
      the recommended six months. As India leads the world in the number of preterm
      births, under 5 years of age malnutrition and neonatal mortality, understanding
      the factors associated with EBF can help improve the nutritional status for
      millions of infants. We assessed the factors associated with EBF in rural Mysore,
      India. Methods: This cross-sectional analysis was nested within a cohort study
      assessing the feasibility and uptake of mobile prenatal care and HIV counseling
      and testing intervention in Mysore District. Multivariable logistic regression
      was used to identify the factors associated with EBF for infants between birth
      and six months. Exclusive breastfeeding was defined as breastfeeding with no
      other liquids or breastfeeding substitutes given to infants exceptfor medicine or
      oral rehydration solution, between birth and 6 months and was assessed at six
      months postpartum. Results: We surveyed mothers who delivered in rural Mysore
      taluk between 2008 and March 2011. A total of 1292 mothers participated in the
      study. The overall breastfeeding rate at six months postpartum was 74.9% and the
      EBF rate was 48.5%. Factors associated with EBF included higher maternal age
      (Adjusted Odds Ratio[aOR] 1.04; 95% Confidence Interval [CI] 1.00, 1.09), lower
      maternal education (aOR1.56, 95% CI 1.10, 2.21), and 7-10 antenatal visits (aOR
      1.57; 95% CI 1.09, 2.27). The most common reason for non-exclusive breastfeeding
      was the mother's feeling that she did not have enough milk (23.7%). Infants that
      were not exclusively breastfed were most commonly fed formula/animal milk (42.6%)
      or castor oil/ghee (18.4%). Conclusions: Less than half of the mothers in our
      sample reported exclusive breastfeeding in a rural region of Karnataka, India in
      the first six months, a rate lower than national and state level rates. Future
      interventions should evaluate whether antenatal education can improve
      breastfeeding outcomes. The only modifiable factor was number of antenatal
      visits. Breastfeeding education should be emphasized at every antenatal visit so
      that even mothers with fewer than 7-10 antenatal visits can learn the best
      techniques and benefits of breastfeeding.

PMID- 30181764
TI  - Protocol: a versatile, inexpensive, high-throughput plant genomic DNA extraction
      method suitable for genotyping-by-sequencing.
AB  - Background: The recent development of next-generation sequencing DNA marker
      technologies, such as genotyping-by-sequencing (GBS), generates thousands of
      informative single nucleotide polymorphism markers in almost any species,
      regardless of genomic resources. This enables poorly resourced or "orphan"
      crops/species access to high-density, high-throughput marker platforms which have
      revolutionised population genetics studies and plant breeding. DNA quality
      underpins success of GBS methods as the DNA must be amenable to restriction
      enzyme digestion and sequencing. A barrier to implementing GBS technologies is
      access to inexpensive, high-throughput extraction methods that yield sequencing
      quality genomic DNA (gDNA) from plants. Several high-throughput DNA extraction
      methods are available, but typically provide low yield or poor quality gDNA, or
      are costly (US$6-$9/sample) for consumables. Results: We modified a non-organic
      solvent protocol to extract microgram quantities (1-13 MUg) of sequencing-quality
      high molecular weight gDNA inexpensively in 96-well plates from either fresh,
      freeze-dried or silica gel-dried plant tissue. The protocol was effective for
      several easy and difficult-to-extract forage, crop, horticultural and common
      model species including Trifolium, Medicago, Lolium, Secale, Festuca, Malus,
      Oryza, and Arabidopsis. The extracted DNA was of high molecular weight and
      digested readily with restriction enzymes. Contrasting with other extraction
      protocols we assessed, Illumina-based sequencing of GBS libraries developed from
      this gDNA had very uniform high quality base-calls to the end of sequence reads.
      Furthermore, DNA extracted using this method has been sequenced successfully with
      the PacBio long-read platform. The protocol is scalable, readily automated
      without requirement for fume hoods, requires approximately three hours to process
      192 samples (384-576 samples/day), and is inexpensive at US$0.62/sample for
      consumables. Conclusions: This versatile, scalable and simple protocol yields
      high molecular weight genomic DNA suitable for restriction enzyme digestion and
      next-generation sequencing applications including GBS and long-read sequencing
      platforms such as PacBio. The low cost, high-throughput, and extraction of high
      quality gDNA from a range of fresh and dried source plant material makes this
      method suitable for many sequencing and genotyping applications including large
      scale sample screening underpinning breeding programmes.

PMID- 30181765
TI  - Estimation of area- and mass-based leaf nitrogen contents of wheat and rice crops
      from water-removed spectra using continuous wavelet analysis.
AB  - Background: The visible and near infrared region has been widely used to estimate
      the leaf nitrogen (N) content based on the correlation of N with chlorophyll and
      deep absorption valleys of chlorophyll in this region. However, most absorption
      features related to N are located in the shortwave infrared (SWIR) region and the
      physical mechanism of leaf N estimation from fresh leaf reflectance spectra
      remains unclear. The use of SWIR region may help us reveal the underlying
      mechanism of casual relationships and better understand the spectral responses to
      N variation from fresh leaf reflectance spectra. This study combined continuous
      wavelet analysis (CWA) and water removal technique to improve the estimation of N
      content and leaf mass per area (LMA) by reducing the effect of water absorption
      and enhancing absorption signals in the SWIR region. The performance of the
      wavelet-based method was evaluated for estimating leaf N content and LMA of rice
      and wheat crops from fresh leaf reflectance spectra collected over a 2-year field
      experiment and compared with normalization difference (ND)-based spectral
      indices. Results: The LMA and area-based N content (Narea) exhibited better
      correlations with the determined wavelet features derived from the water-removed
      (WR) spectra (LMA: R2 = 0.71, Narea: R2 = 0.77) than those from the measured
      reflectance (MR) spectra (LMA: R2 = 0.62, Narea: R2 = 0.64). The wavelet features
      performed remarkably better than the optimized ND indices for the estimations of
      LMA and Narea with MR spectra or WR spectra. Based on the best estimations of LMA
      and Narea with wavelet features from WR spectra, the mass-based N content (Nmass)
      could be retrieved with a high accuracy (R2 = 0.82, RMSE = 0.32%) in the indirect
      way. This accuracy was higher than that for Nmass obtained in the direct use of a
      single wavelet feature (R2 = 0.68, RMSE = 0.42%). Conclusions: The enhancement of
      absorption features in the SWIR region through the CWA applied to water-removed
      (WR) spectra was able to improve the spectroscopic estimation of leaf N content
      and LMA as compared to that obtained with the reflectance spectra of fresh
      leaves. The success in estimating LMA and N with this method would advance the
      spectroscopic estimations of grain quality parameters for staple crops and
      individual dry matter constituents for various vegetation types.

PMID- 30181766
TI  - A low-cost method to rapidly and accurately screen for transpiration efficiency
      in wheat.
AB  - Background: Wheat (Triticum aestivum L.) productivity is commonly limited by the
      availability of water. Increasing transpiration efficiency (biomass produced per
      unit of water used, TE) can potentially lead to increased grain yield in water
      limited environments ('more crop per drop'). Currently, the ability to screen
      large populations for TE is limited by slow, low-throughput and/or expensive
      screening procedures. Here, we propose a low-cost, low-technology, rapid, and
      scalable method to screen for TE. The method uses a Pot-in-Bucket system that
      allows continuous watering of the pots and frequent monitoring of water use. To
      investigate the robustness of the method across environments, and to determine
      the shortest trial duration required to get accurate and repeatable TE estimates
      in wheat, plants from 11 genotypes varying in phenology were sown at three dates
      and grown for different durations in a polyhouse with partial environmental
      control. Results: The method revealed significant genotypic variations in TE
      among the 11 studied wheat genotypes. Genotype rankings for TE were consistent
      when plants were harvested the same day, at the flag-leaf stage or later. For
      these harvests, genotype rankings were consistent across experiments despite
      changes in environmental conditions, such as evaporative demand. Conclusions:
      These results indicate that (1) the Pot-In-Bucket system is suitable to screen TE
      for breeding purposes in populations with varying phenology, (2) multiple short
      trials can be carried out within a season to allow increased throughput of
      genotypes for TE screening, and (3) root biomass measurement is not required to
      screen for TE, as whole-plant TE and shoot-only TE are highly correlated, at
      least in wheat. The method is particularly relevant in developing countries where
      low-cost and relatively high labour input may be most applicable.

PMID- 30181767
TI  - Improved de novo peptide sequencing using LC retention time information.
AB  - Background: Liquid chromatography combined with tandem mass spectrometry is an
      important tool in proteomics for peptide identification. Liquid chromatography
      temporally separates the peptides in a sample. The peptides that elute one after
      another are analyzed via tandem mass spectrometry by measuring the mass-to-charge
      ratio of a peptide and its fragments. De novo peptide sequencing is the problem
      of reconstructing the amino acid sequences of a peptide from this measurement
      data. Past de novo sequencing algorithms solely consider the mass spectrum of the
      fragments for reconstructing a sequence. Results: We propose to additionally
      exploit the information obtained from liquid chromatography. We study the problem
      of computing a sequence that is not only in accordance with the experimental mass
      spectrum, but also with the chromatographic retention time. We consider three
      models for predicting the retention time and develop algorithms for de novo
      sequencing for each model. Conclusions: Based on an evaluation for two prediction
      models on experimental data from synthesized peptides we conclude that the
      identification rates are improved by exploiting the chromatographic information.
      In our evaluation, we compare our algorithms using the retention time information
      with algorithms using the same scoring model, but not the retention time.

PMID- 30181768
TI  - Introduction of a mass burn casualty triage system in a hospital during a powder
      explosion disaster: a retrospective cohort study.
AB  - Background: The triage system used during an actual mass burn casualty (MBC)
      incident is a major focus of concern. This study introduces a MBC triage system
      that was used by a burn center during an actual MBC incident following a powder
      explosion in New Taipei City, Taiwan. Methods: This study retrospectively
      analyzed data from patients who were sent to the study hospital during a MBC
      incident. The patient list was retrieved from a national online management
      system. A MBC triage system was developed at the study hospital using the
      following modifiers: consciousness, breathing, and burn size. Medical records
      were retrieved from electronic records for analysis. Patient outcomes consisted
      of emergency department (ED) disposition and intervention. Results: The patient
      population was predominantly female (56.3%), with an average age of 24.9 years.
      Mean burn sizes relative to the TBSA of triage level I, II, and III patients were
      57.9%, 40.5%, and 8.7%, respectively. ICU length of stay differed markedly
      according to triage level (mean days for levels I vs II vs III: 57.9 vs 39.9 vs
      2.5 days; p < 0.001). Triage system levels I and II indicate ICU admission with a
      sensitivity of 93.9% (95%CI 80.4-98.3%) and a specificity of 86.7% (62.1
      96.3%).Overall, 3 (6.3%) patients were under-triaged. Two (4.2%) patients were
      over-triaged. Sixteen (48.5%) and 21 (63.6%) patients of triage levels I and II
      received endotracheal intubation and central venous catheterization,
      respectively. Sorting of the study population with simple triage and rapid
      treatment (START) showed great sensitivity (100.0%) but poor specificity (53.3%).
      The Taiwan Triage and Acuity Scale (TTAS) presented 87.9% sensitivity and 93.9%
      specificity. Conclusions: The current MBC triage algorithm served as a good
      indicator of ED disposition but might have raised excessive immediate attention
      and had the potential to exhaust the available resources. These findings add to
      our knowledge of the MBC triage system and should help future researchers in
      adjusting the triage criteria to fit actual disasters.

PMID- 30181769
TI  - Anti-cancer effects of Rhizoma Curcumae against doxorubicin-resistant breast
      cancer cells.
AB  - Background: Chemotherapy is a primary approach in cancer treatment after routine
      surgery. However, chemo-resistance tends to occur with chemotherapy in clinic,
      resulting in poor prognosis and recurrence. Nowadays, Chinese medicine may shed
      light on design of new therapeutic modes to overcome chemo-resistance. Although
      Rhizoma Curcumae possesses anti-cancer activities in various types of cancers,
      the effects and underlying mechanisms of its bioactive components against chemo
      resistance are not clear. Therefore, the present study aims to explore the
      potential effects of Rhizoma Curcumae on doxorubicin-resistant breast cancer
      cells. Methods: The expression and function of ABC transporters in doxorubicin
      resistant MCF-7 breast cancer cells were measured by western blotting and flow
      cytometry. Cell viability was detected using MTT assay. The combination index was
      analyzed using the CalcuSyn program (Biosoft, Ferguson, MO), based on the Chou
      Talalay method. Results: In our present study, P-gp was overexpressed at protein
      level in doxorubicin-resistant MCF-7 cell line, but short of MRP1 and BCRP1.
      Essential oil of Rhizoma Curcumae and the main bioactive components were assessed
      on doxorubicin-resistant MCF-7 cell line. We found that the essential oil and
      furanodiene both display powerful inhibitory effects on cell viability, but
      neither of these is the specific inhibitor of ABC transporters. Moreover,
      furanodiene fails to enhance the efficacy of doxorubicin to improve multidrug
      resistance. Conclusion: Overall, our findings fill the gaps of the researches on
      chemo-resistance improvement of Rhizoma Curcumae and are also beneficial for
      Rhizoma Curcumae being developed as a promising natural product for cancer
      adjuvant therapy in the future.

PMID- 30181770
TI  - Wnt5a mediates the effects of Bushen Huoxue decoction on the migration of bone
      marrow mesenchymal stem cells in vitro.
AB  - Background: Bushen Huoxue decoction (BHD) has a significant effect on fracture
      rehabilitation, yet its underlying mechanism is still unknown. The purpose of
      this study was to explore whether BHD promotes bone marrow mesenchymal stem cell
      (BMSC) migration through the Wnt5a signalling pathway. Methods: BHD was extracted
      by petroleum, and its composition was analysed. Cell viability in the presence of
      various concentrations of BHD for 24, 48 and 72 h was measured using a Cell
      Counting Kit-8 assay. Transwell assays and wound healing assays were used to
      observe the migration ability of BMSCs. Lentiviral vectors were used to knock
      down Wnt5a. Polymerase chain reaction and Western blot analyses were used to
      further compare Wnt5a signalling components at the mRNA and protein levels
      between groups. Results: BHD treatment groups showed increased migration ability
      and Wnt5a expression. Knocking down Wnt5a using a lentivirus significantly
      inhibited the effects of BHD, which implies that BHD promotes BMSC migration
      ability through activation of Wnt5a. Conclusions: BHD can enhance BMSC migration,
      possibly by activating Wnt5a signalling.

PMID- 30181771
TI  - A network pharmacology approach to explore the mechanisms of Erxian decoction in
      polycystic ovary syndrome.
AB  - Background: Polycystic ovary syndrome (PCOS) significantly affects women's health
      and well-being. To explore the pharmacological basis of the Erxian decoction
      (EXD) action in PCOS therapy, a network interaction analysis was conducted at the
      molecular level. Methods: The active elements of EXD were identified according to
      the oral bioavailability and drug-likeness filters from three databases:
      traditional Chinese medicine system pharmacology analysis platform, TCM@taiwan
      and TCMID, and their potential targets were also identified. Genes associated
      with PCOS and established protein-protein interaction networks were mined from
      the NCBI database. Finally, significant pathways and functions of these networks
      were identified using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes
      analyses to determine the mechanism of action of EXD. Results: Seventy active
      compounds were obtained from 981 ingredients present in the EXD decoction,
      corresponding to 247 targets. In addition, 262 genes were found to be closely
      related with PCOS, of which 50 overlapped with EXD and were thus considered
      therapeutically relevant. Pathway enrichment analysis identified PI3k-Akt,
      insulin resistance, Toll-like receptor, MAPK and AGE-RAGE from a total of 15
      significant pathways in PCOS and its treatment. Conclusions: EXD can effectively
      improve the symptoms of PCOS and our systemic pharmacological analysis lays the
      experimental foundation for further clinical applications of EXD.

PMID- 30181772
TI  - Tenofovir disoproxil fumarate reduce incidence of HCC development in CHB-patients
      with compensated cirrhosis.
AB  - Background: The impact of different anti-virus regimens on prognosis of Chronic
      hepatitis B (CHB) related cirrhosis remains to be explored. We aim to investigate
      whether CHB-related HCC patients receiving nucleoside analogue regimen or not
      have a different prognosis. Methods: Two hundred forty-two CHB-related
      compensated cirrhosis patients were attributed into groups regarding their anti
      virus regimens containing tenofovir disoproxil fumarate (TDF) or not. The results
      of two groups were reviewed and investigated. The probability of hepatocellular
      carcinoma (HCC) development among each group were analyzed and compared. Results:
      Two hundred forty-two CHB-related compensated cirrhosis patients from 2008 June
      to 2011 December were included in our study. One hundred twenty-seven patients
      received anti-virus regimen containing TDF and 115 patients received anti-virus
      regimen without TDF. Child-Pugh score, alanine aminotransferase (ALT), total
      bilirubin level, status of hepatitis B e antigen (HBeAg) and serum HBV DNA level
      were compared between groups. The cumulative probability of HCC development in
      TDF-contained group were significantly lower than it in non-TDF-contained group
      (p < 0.05). Multi-variant analysis indicated that TDF-containing regimen
      treatment was significantly associated with lower probability of HCC development,
      (hazard ratio, 0.18; 95% confidence interval range, 0.07-0.45, p < 0.05).
      Conclusion: Anti-virus regimen containing TDF benefits for the prognosis of CHB
      related liver cirrhosis patients.

PMID- 30181773
TI  - Improvement of anaerobic digestion of sewage mixed sludge using free nitrous acid
      and Fenton pre-treatment.
AB  - Background: Recently, it has been indicated that free nitrous acid (FNA) and
      Fenton pre-treatment of waste activated sludge can enhance methane production in
      anaerobic digestion of waste activated sludge. In addition, it has been revealed
      that the substances used in these pre-treatments are both eco-friendly and
      economically attractive because not only are they produced in anaerobic
      digestion, but they are also low priced. Since primary sludge and waste activated
      sludge are mixed prior to anaerobic digestion in the majority of wastewater
      treatment plants, this study aims to assess the influence of combined FNA and
      Fenton on the anaerobic digestion of mixed sludge. Results: According to this
      study's results, methane generation from anaerobic digestion of mixed sludge was
      enhanced when using FNA and Fenton pre-treatment, affirming the effectiveness of
      the individual and combined pre-treatments in anaerobic digestion of mixed
      sludge. The enhanced methane production was significant in combined pre
      treatments (up to 72%), compared with FNA and Fenton pre-treatment alone (25% and
      27%, respectively). This corroborates the positive synergistic effect of the
      combined pre-treatments on methane production. The enhanced methane can be
      attributed to augmented soluble fractions of organic matter in addition to
      increased readily biodegradable organic matter, caused by the pre-treatments.
      Additionally, the amount of chemical oxygen demand (COD) was assessed during
      anaerobic digestion, and it was revealed that COD decreased considerably when the
      pre-treatment strategies were combined. Conclusions: This study reveals that the
      pre-treatments are potentially applicable to full-scale wastewater treatment
      plants because a mixture of primary sludge and waste activated sludge was used
      for the pre-treatments. Additionally, combined FNA and Fenton pre-treatments
      prove more effective in enhancing methane production and organic removal than
      these pre-treatments alone. The enhanced methane production is important for two
      reasons: a higher amount of renewable energy could be generated from the enhanced
      methane production and the COD of digested sludge reduces in such a way that
      facilitates application of the sludge to agricultural lands and reduces sludge
      transport costs.

PMID- 30181775
TI  - Efficient metabolic evolution of engineered Yarrowia lipolytica for succinic acid
      production using a glucose-based medium in an in situ fibrous bioreactor under
      low-pH condition.
AB  - Background: Alkali used for pH control during fermentation and acidification for
      downstream recovery of succinic acid (SA) are the two largest cost contributors
      for bio-based SA production. To promote the commercialization process of
      fermentative SA, the development of industrially important microorganisms that
      can tolerate low pH has emerged as a crucial issue. Results: In this study, an in
      situ fibrous bed bioreactor (isFBB) was employed for the metabolic evolution for
      selection of Y. lipolytica strain that can produce SA at low pH using glucose
      based medium. An evolved strain named Y. lipolytica PSA3.0 that could produce SA
      with a titer of 19.3 g/L, productivity of 0.52 g/L/h, and yield of 0.29 g/g at pH
      3.0 from YPD was achieved. The enzyme activity analysis demonstrated that the
      pathway from pyruvate to acetate was partially blocked in Y. lipolytica PSA3.0
      after the evolution, which is beneficial to cell growth and SA production at low
      pH. When free-cell batch fermentations were performed using the parent and
      evolved strains separately, the evolved strain PSA3.0 produced 18.4 g/L SA with a
      yield of 0.23 g/g at pH 3.0. Although these values were lower than that obtained
      by the parent strain PSA02004 at its optimal pH 6.0, which were 25.2 g/L and 0.31
      g/g, respectively, they were 4.8 and 4.6 times higher than that achieved by
      PSA02004 at pH 3.0. By fed-batch fermentation, the resultant SA titer of 76.8 g/L
      was obtained, which is the highest value that ever achieved from glucose-based
      medium at low pH, to date. When using mixed food waste (MFW) hydrolysate as
      substrate, 18.9 g/L SA was produced with an SA yield of 0.38 g/g, which
      demonstrates the feasibility of using low-cost glucose-based hydrolysate for SA
      production by Y. lipolytica in a low-pH environment. Conclusions: This study
      presents an effective and efficient strategy for the evolution of Y. lipolytica
      for SA production under low-pH condition for the first time. The isFBB was
      demonstrated to improve the metabolic evolution efficiency of Y. lipolytica to
      the acidic condition. Moreover, the acetate accumulation was found to be the
      major reason for the inhibition of SA production at low pH by Y. lipolytica,
      which suggested the direction for further metabolic modification of the strain
      for improved SA production. Furthermore, the evolved strain Y. lipolytica PSA3.0
      was demonstrated to utilize glucose-rich hydrolysate from MFW for fermentative SA
      production at low pH. Similarly, Y. lipolytica PSA3.0 is expected to utilize the
      glucose-rich hydrolysate generated from other carbohydrate-rich waste streams for
      SA production. This study paves the way for the commercialization of bio-based SA
      and contributes to the sustainable development of a green economy.

PMID- 30181774
TI  - Bio-production of gaseous alkenes: ethylene, isoprene, isobutene.
AB  - To reduce emissions from petrochemical refinement, bio-production has been
      heralded as a way to create economically valuable compounds with fewer harmful
      effects. For example, gaseous alkenes are precursor molecules that can be
      polymerized into a variety of industrially significant compounds and have
      biological production pathways. Production levels, however, remain low, thus
      enhancing bio-production of gaseous petrochemicals for chemical precursors is
      critical. This review covers the metabolic pathways and production levels of the
      gaseous alkenes ethylene, isoprene, and isobutene. Techniques needed to drive
      production to higher levels are also discussed.

PMID- 30181776
TI  - Complications of pelvic and acetabular fractures in 1331 morbidly obese patients
      (BMI >= 40): a retrospective observational study from the National Trauma Data
      Bank.
AB  - Background: There have been no large-scale epidemiological studies of outcomes
      and perioperative complications in morbidly obese trauma patients who have
      sustained closed pelvic ring or acetabular fractures. We examined this population
      and compared their rate of inpatient complications with that of control patients.
      Methods: We retrospectively reviewed the records of patients treated for closed
      pelvic ring or acetabular fracture, aged 16-85 years, with Injury Severity Scores
      <=15 from the National Trauma Data Bank Research Dataset for the years 2007
      through 2010. The primary outcome of interest was rate of in-hospital
      complications. Secondary outcomes were length of hospital stay and discharge
      disposition. Unadjusted differences in complication rates were evaluated using
      Student t tests and Chi-squared analyses. Multiple logistic and Poisson
      regression were used to analyze binary outcomes and length of hospital stay,
      respectively, adjusting for several variables. Statistical significance was
      defined as p < 0.05. Results: We included 46,450 patients in our study. Of these
      patients, 1331 (3%) were morbidly obese (body mass index >=40) and 45,119 (97%)
      were used as controls. Morbidly obese patients had significantly higher odds of
      complication and longer hospital stay in all groups considered except those with
      pelvic fractures that were treated operatively. In all groups, morbidly obese
      patients were more likely to be discharged to a skilled nursing/rehabilitation
      facility compared with control patients. Conclusions: Morbidly obese patients had
      higher rates of complications and longer hospital stays and were more likely to
      be discharged to rehabilitation facilities compared with control patients after
      pelvic ring or acetabular fracture.

PMID- 30181777
TI  - Stable transmission of an unbalanced chromosome 21 derived from
      chromoanasynthesis in a patient with a SYNGAP1 likely pathogenic variant.
AB  - Background: Complex genomic structural variations, involving chromoanagenesis,
      have been implicated in multiple congenital anomalies and abnormal
      neurodevelopment. Familial inheritance of complex chromosomal structural
      alteration resulting from germline chromoanagenesis-type mechanisms are limited.
      Case presentation: We report a two-year eleven-month old male presenting with
      epilepsy, ataxia and dysmorphic features of unknown etiology. Chromosomal
      microarray identified a complex unbalanced rearrangement involving chromosome 21.
      G-banding and FISH for targeted regions of chromosome 21 revealed that the copy
      number imbalances were limited to gains dispersed throughout the long arm of
      chromosome 21, characteristic of a chromosome derived from chromoanagenesis.
      Family studies showed that the unbalanced chromosome had been stably inherited,
      as it was present in both his healthy mother and maternal grandfather. Further
      molecular testing for non-syndromic intellectual disability genes found a likely
      pathogenic mutation in SYNGAP1 (NM_006772.2:c.3722_3723del). Conclusions: This
      study indicates that complex rearrangements involving an unbalanced chromosome
      derived from chromoanasynthesis can be familial and should be not be presumed
      pathogenic.

PMID- 30181778
TI  - Long-term outcomes of peginterferon beta-1a in multiple sclerosis: results from
      the ADVANCE extension study, ATTAIN.
AB  - Background: ADVANCE was a phase III trial of the efficacy and safety of
      subcutaneous peginterferon beta-1a 125 ug every 2 or 4 weeks in patients with
      relapsing-remitting multiple sclerosis (RRMS). ATTAIN was a 2-year extension
      study of ADVANCE. The aim was to evaluate the long-term safety, tolerability, and
      efficacy of peginterferon beta-1a 125 ug every 2 or 4 weeks in ATTAIN. Methods:
      ADVANCE dosing schedules were maintained in ATTAIN, except that every-4-weeks
      dosing patients were switched to every-2-weeks dosing after conversion of the
      study to an open-label protocol. ATTAIN was considered complete when the last
      patient completed the 96-week extension study. Primary endpoints included adverse
      event (AE) and serious AE (SAE) incidence. Secondary endpoints included relapse,
      magnetic resonance imaging, and disability outcomes. Results: Of the 1512
      patients randomized in ADVANCE, 1076 (71%) continued treatment in ATTAIN; of
      these, 842 (78%) completed the open-label extension study. During ATTAIN, 478
      patients (87%) in the every-2-weeks group and 471 patients (89%) in the every-4
      weeks group experienced an AE; SAEs were reported in 90 patients (16%) in the
      every-2-weeks group and 113 patients (21%) in the every-4-weeks group. The most
      frequent AEs reported were injection site reactions and flu-like symptoms, both
      of which numerically decreased over time. Peginterferon beta-1a every 2 weeks
      versus every 4 weeks significantly reduced the adjusted annualized relapse rate
      over 6 years (0.188 versus 0.263, p = 0.0052) and the risk of relapse over 5
      years (36% versus 49%, p = 0.0018). Fewer new T1, new/newly enlarging T2, and
      gadolinium-enhancing magnetic resonance imaging lesions were observed with every
      2-weeks dosing than every-4-weeks dosing over 4 years. Conclusions: Results from
      the ADVANCE extension study, ATTAIN, confirm the favorable long-term safety and
      tolerability profile of peginterferon beta-1a in patients with RRMS and provide
      additional evidence for the clinical and radiological benefits associated with
      this therapy.

PMID- 30181780
TI  - Peginterferon beta-1a every 2 weeks increased achievement of no evidence of
      disease activity over 4 years in the ADVANCE and ATTAIN studies in patients with
      relapsing-remitting multiple sclerosis.
AB  - Background: No evidence of disease activity (NEDA) is a composite measurement,
      incorporating clinical and magnetic resonance imaging (MRI) elements of disease
      activity to sensitively evaluate the therapeutic efficacy of treatments for
      relapsing-remitting multiple sclerosis (RRMS). Objective: To assess the NEDA
      status of patients treated with peginterferon beta-1a in the ADVANCE and ATTAIN
      studies and explore its predictive value on longer-term clinical outcomes.
      Methods: ATTAIN was a 2-year extension of the pivotal 2-year ADVANCE study of
      peginterferon beta-1a for RRMS. Achievement of clinical NEDA, MRI NEDA, or
      overall NEDA was calculated cumulatively and by year over 4 years. Clinical
      outcomes during ATTAIN were analyzed based on NEDA status at the end of ADVANCE.
      Results: Significantly more patients treated with peginterferon beta-1a every 2
      weeks than every 4 weeks achieved clinical NEDA (60.6% versus 50.6%, p = 0.0063)
      and MRI NEDA (28.3% versus 15.8%, p = 0.0005) through year 4 and overall NEDA
      through year 3 (20.9% versus 13.9%, p = 0.0160). Over 4 years, 15.8% of patients
      in the every 2 weeks group and 10.7% of patients in the every 4 weeks group
      maintained overall NEDA (p = 0.0584). Achievement of clinical NEDA, MRI NEDA, or
      overall NEDA in ADVANCE was predictive of annualized relapse rate in ATTAIN;
      achievement of clinical NEDA in ADVANCE was also predictive of NEDA achievement
      and confirmed disability worsening in ATTAIN. Conclusions: Peginterferon beta-1a
      every 2 weeks is associated with higher levels of NEDA compared with placebo in
      year 1 or peginterferon beta-1a every 4 weeks in years 2-4. Overall NEDA within
      the first 2 years of treatment may be prognostic of long-term clinical
      outcomes.Clinicaltrials.gov: NCT01332019.

PMID- 30181779
TI  - Ischemia-reperfusion injury in stroke: impact of the brain barriers and brain
      immune privilege on neutrophil function.
AB  - Reperfusion injury following ischemic stroke is a complex pathophysiological
      process involving numerous mechanisms ranging from the release of excitatory
      amino acids and ion disequilibrium to the induction of apoptosis and necrosis, to
      oxidative stress and inflammation. The migration of neutrophils into the brain
      parenchyma and release of their abundant proteases are generally considered the
      main cause of neuronal cell death and acute reperfusion injury following ischemic
      stroke. Recent findings in experimental and human stroke have challenged this
      view, as the majority of neutrophils were rather found to accumulate within the
      neurovascular unit (NVU) and the subarachnoid space (SAS) where they remain
      separated from the brain parenchyma by the glia limitans. The brain parenchyma is
      an immune-privileged site that is not readily accessible to immune cells and does
      not elicit stereotypic adaptive or innate immune responses. Understanding brain
      immune privilege requires intimate knowledge of its unique anatomy in which the
      brain barriers, that include the glia limitans, establish compartments that
      differ remarkably with regard to their accessibility to the immune system. We
      here propose that the brain immune privilege also extends to an ischemic insult,
      where the brain parenchyma does not evoke a rapid infiltration of neutrophils as
      observed in ischemic events in peripheral organs. Rather, neutrophil accumulation
      in the NVU and SAS could have a potential impact on cerebrospinal fluid (CSF)
      drainage from the central nervous system (CNS) and thus on edema formation and
      reperfusion injury after ischemic stroke. Integrating the anatomical and
      functional implications of the brain immune privilege with the unquestionable
      role of neutrophils in reperfusion injury is a prerequisite to exploit
      appropriate strategies for therapeutic interventions aiming to reduce neuronal
      cell death after ischemic stroke.

PMID- 30181781
TI  - Phylogenetic characterization of norovirus strains detected from sporadic
      gastroenteritis in Seoul during 2014-2016.
AB  - Background: Phylogenetic analysis of norovirus (NoV) is efficient for tracking
      NoV transmission. To determine the widespread NoV strains in Seoul, we conducted
      an extensive phylogenetic characterization of NoV-positives from 1659 diarrheal
      specimens collected in 2014-2016 for the Seoul NoV-surveillance. Results: When
      the large numbers of NoV partial VP1 genome sequences were analyzed in acute
      gastroenteritis patients along with the phylogenetic characterization, we could
      identify molecular epidemiologic patterns based on the genetic characteristics of
      sporadic NoV strains circulating in Seoul, which could provide a detailed
      description of the genome-wide and community-wide NoV evolution in each genotype.
      The average NoV detection rate in our study period was 16.34% that was increased
      by 7.44% from 13.17% in 2014 to 20.61% in 2016. Prevalence of NoV GI and GII was
      4.43% and 93.36%, respectively, and the GII.4, GII.17, and GII.3 were found to be
      the major type among 17 genotypes of NoV. The most prevalent one was GII.4
      (50.92%) that was followed by GII.17 (18.08%) and GII.3 (9.96%). According to an
      extensive phylogenetic analysis based on partial VP1 sequences of 1008 NoV (276
      sporadic, 518 outbreak and 214 reference), pandemic strains of GII.17, GII.4 and
      GII.3 have emerged in succession during the 2014-2016 Seoul NoV-surveillance.
      GII.17 emerged as GII.17|Kawasaki323 in 2014, and became the predominant genotype
      in 2015 with GII.17|2014_Kawasaki lineages (CUHK-NS-616/Kawasaki308). The
      formerly predominant GII.4 remained high-level with GII.4|2012_Sydney in 2014 and
      internally replaced to GII.4|2016_Kawasaki194 lineage (NOR-2565/NOR-2558/OH16002)
      that caused the sporadic NoV explosion since December 2015. Sporadically
      prevalent GII.3|Hu/Aichio334-13/2013 failed to develop any outbreaks, whereas
      sporadic GII.3|Hu/3-28/2015/HNZZ/CHN caused heavy outbreaks in Seoul without
      preparation time since November 2016. Conclusions: This is the first extensive
      phylogenetic study revealing the important events of NoV strains circulating in
      Seoul. Particularly, our study period from 2014 to 2016 was very dynamic with the
      emergences of the three main NoV strains (GII.17|2014_Kawasaki,
      GII.4|2016_Kawasaki194 and GII.3|Hu/3-28/2015/HNZZ/CHN) every year. We are sure
      that it is hard to detect above findings by simple conventional analysis. Our
      present study reports a future paradigm of the NoV molecular epidemiology, which
      might be highly valuable to track new strains and predict oncoming outbreaks.

PMID- 30181783
TI  - Imatinib rechallenge in patients with advanced gastrointestinal stromal tumors
      following progression with imatinib, sunitinib and regorafenib.
AB  - Background: Rechallenge with imatinib is an option in advanced gastrointestinal
      stromal tumor (GIST) patients following progression with standard tyrosine-kinase
      inhibitors (TKIs), imatinib, sunitinib and regorafenib. We retrospectively
      collected data from metastatic Italian GIST patients treated with imatinib
      resumption after progression to conventional TKIs. Methods: A total of 104
      eligible advanced GIST patients, previously treated with imatinib, sunitinib and
      regorafenib, were collected from six referral Italian institutions. Mutational
      analysis was recorded and correlated with survival and response according to
      RECIST 1.1 or CHOI criteria. Results: Overall, 71 patients treated with imatinib
      400 mg as rechallenge were included. Mutational status was available in all
      patients. The median follow up was 13 months. In patients who received a
      rechallenge therapy, the median time to progression (TTP) was 5.4 months [95%
      confidence interval (CI) 1.9-13.5] and overall survival (OS) was 10.6 months (95%
      CI 2.8-26.9). A correlation between mutational status, response rate, TTP and OS
      was not found but comparing deleted versus nondeleted KIT exon 11 patients, a
      significant difference was identified in terms of TTP and OS (p = 0.04 and p =
      0.02, respectively). Conclusions: Our retrospective data confirm that imatinib
      rechallenge is a reasonable option in advanced GIST. The prognostic value of the
      specific KIT mutations was confirmed in our series.

PMID- 30181782
TI  - Activation of viral defense signaling in cancer.
AB  - A coordinated action of innate and adaptive immune responses is required to
      efficiently combat a microbial infection. It has now become clear that cancer
      therapies also largely benefit when both arms of the immune response are engaged.
      In this review, we will briefly describe the current knowledge of innate immunity
      and how this can be utilized to prime tumors for a better response to immune
      checkpoint inhibitors. Comments on compounds in development and ongoing clinical
      trials will be provided.

PMID- 30181784
TI  - Towards precision medicine: linking genetic and cellular heterogeneity in gastric
      cancer.
AB  - Molecular and cellular heterogeneity are phenomena that are revolutionizing
      oncology research and becoming critical to the idea of personalized medicine.
      Recent comprehensive molecular profiling has identified molecular subtypes of
      gastric cancer (GC) and linked them to clinical information. Moreover, GC stem
      cells (gCSCs) have been identified and found to be responsible for GC initiation
      and progression, Helicobacter pylori oncogenic action and therapy resistance.
      Addressing molecular heterogeneity is critical for achieving an optimal
      therapeutic approach against GC as well as targeting gCSCs. In this review, we
      outline the implications of molecular and cellular heterogeneity in the treatment
      of GC and we summarize the clinical impact of the most important regulators of
      gCSCs.

PMID- 30181787
TI  - Insertion sequence elements-mediated structural variations in bacterial genomes.
AB  - Mobile genetic elements (MGEs) impact the evolution and stability of their host
      genomes. Insertion sequence (IS) elements are the most common MGEs in bacterial
      genomes and play a crucial role in mediating large-scale variations in bacterial
      genomes. It is understood that IS elements and MGEs in general coexist in a
      dynamical equilibrium with their respective hosts. Current studies indicate that
      the spontaneous movement of IS elements does not follow a constant rate in
      different bacterial genomes. However, due to the paucity and sparsity of the
      data, these observations are yet to be conclusive. In this paper, we conducted a
      comparative analysis of the IS-mediated genome structural variations in ten
      mutation accumulation (MA) experiments across eight strains of five bacterial
      species containing IS elements, including four strains of the E. coli. We used
      GRASPER algorithm, a denovo structural variation (SV) identification algorithm
      designed to detect SVs involving repetitive sequences in the genome. We observed
      highly diverse rates of IS insertions and IS-mediated recombinations across
      different bacterial species as well as across different strains of the same
      bacterial species. We also observed different rates of the elements from the same
      IS family in different bacterial genomes, suggesting that the distinction in
      rates might not be due to the different composition of IS elements across
      bacterial genomes.

PMID- 30181786
TI  - Inflammation, obesity and rheumatic disease: common mechanistic links. A
      narrative review.
AB  - Obesity represents a rising global health concern, linked to significant social,
      psychological and physical burden to the individual affected, people around them
      and the society as a whole. Obesity has been described as a low-grade
      inflammatory condition, associated with increased production of pro-inflammatory
      mediators like tumor necrosis factor alpha or interleukin 6 and altered
      expression of adipokines. Adipokines, mainly produced by adipose tissue, have
      mixed pro- and anti-inflammatory properties. Obesity rarely exists on its own;
      instead, it tends to coexist with (often multiple) other comorbidities, including
      metabolic, cardiovascular, and rheumatic and musculoskeletal diseases (RMDs). In
      the case of RMDs, evidence is rapidly accumulating on common mechanistic pathways
      implicated in the inflammatory states seen between RMDs and obesity. Although
      there remain unanswered questions on the exact mechanisms of inflammation that
      link obesity to RMDs, what is becoming increasingly known is the association
      between obesity and adverse clinical outcomes in RMDs. This narrative review
      discusses insights into mechanisms of inflammation linking obesity and RMDs and
      evidence on the impact of obesity on treatment response and important disease
      outcomes. We highlight the importance of targeting obesity, a common and
      modifiable comorbidity, as part of the routine care of people with RMDs.

PMID- 30181785
TI  - Liquid biopsy of cancer: a multimodal diagnostic tool in clinical oncology.
AB  - Over the last decades, the concept of precision medicine has dramatically renewed
      the field of medical oncology; the introduction of patient-tailored therapies has
      significantly improved all measurable outcomes. Liquid biopsy is a revolutionary
      technique that is opening previously unexpected perspectives. It consists of the
      detection and isolation of circulating tumor cells, circulating tumor DNA and
      exosomes, as a source of genomic and proteomic information in patients with
      cancer. Many technical hurdles have been resolved thanks to newly developed
      techniques and next-generation sequencing analyses, allowing a broad application
      of liquid biopsy in a wide range of settings. Initially correlated to prognosis,
      liquid biopsy data are now being studied for cancer diagnosis, hopefully
      including screenings, and most importantly for the prediction of response or
      resistance to given treatments. In particular, the identification of specific
      mutations in target genes can aid in therapeutic decisions, both in the
      appropriateness of treatment and in the advanced identification of secondary
      resistance, aiming to early diagnose disease progression. Still application is
      far from reality but ongoing research is leading the way to a new era in
      oncology. This review summarizes the main techniques and applications of liquid
      biopsy in cancer.

PMID- 30181788
TI  - A perspective on using experiment and theory to identify design principles in dye
      sensitized solar cells.
AB  - Dye-sensitized solar cells (DSCs) have been the subject of wide-ranging studies
      for many years because of their potential for large-scale manufacturing using
      roll-to-roll processing allied to their use of earth abundant raw materials. Two
      main challenges exist for DSC devices to achieve this goal; uplifting device
      efficiency from the 12 to 14% currently achieved for laboratory-scale 'hero'
      cells and replacement of the widely-used liquid electrolytes which can limit
      device lifetimes. To increase device efficiency requires optimized dye injection
      and regeneration, most likely from multiple dyes while replacement of liquid
      electrolytes requires solid charge transporters (most likely hole transport
      materials - HTMs). While theoretical and experimental work have both been widely
      applied to different aspects of DSC research, these approaches are most effective
      when working in tandem. In this context, this perspective paper considers the key
      parameters which influence electron transfer processes in DSC devices using one
      or more dye molecules and how modelling and experimental approaches can work
      together to optimize electron injection and dye regeneration.

PMID- 30181790
TI  - Social attitude and willingness to attend cardiopulmonary resuscitation training
      and perform resuscitation in the Crimea.
AB  - BACKGROUND: To promote potentially life-saving bystander cardiopulmonary
      resuscitation (CPR), the proportion of CPR-trained general public and their
      attitude toward CPR should be assessed, which is yet to be done in the former
      Soviet Union countries. As a case study, the survey is aimed to investigate the
      prevalence of CPR training, CPR knowledge, attitude and willingness to attend
      training and attempt CPR in the general population of the Crimea. METHODS: A
      personal interview survey was done from November 2017 to January 2018 with quota
      sampling reflecting age, gender and territorial distribution of the Crimean
      population. RESULTS: Out of 384 persons surveyed, 53% were trained in CPR. Of
      trained, 24% passed training within the last year, 44% attended a single course.
      Among the non-trained, 51% never thought about the need to attend training.
      Knowledge of CPR is generally poor. About 52% wish to learn CPR, 79% and 91% are
      willing to attempt CPR on a stranger or a loved one, respectively. Lack of
      knowledge is the strongest barrier to attempt CPR. People aged >=60, those with
      educational level lower than high school, widowed and retired are mostly
      untrained and unwilling to learn CPR. Females and unemployed are mostly
      untrained, but willing to be educated. CONCLUSION: There is a need for increasing
      CPR training and retraining, and improving awareness and motivation to learn CPR
      in the Crimean population, targeting the least trained groups. The results could
      be used as a reference point for future studies in the former USSR countries,
      utilising the same methodology.

PMID- 30181791
TI  - Sub-dissociative dose ketamine administration for managing pain in the emergency
      department.
AB  - BACKGROUND: We describe our experience of utilizing sub-dissociative dose
      ketamine (SDK) in managing a variety of acute and chronic painful conditions in
      the emergency department (ED). METHODS: A descriptive study was conducted in our
      ED over a period of seven years (2010-2016) by retrospectively reviewing charts
      of patients aged 18 and older presenting to the ED with painful complaints and
      receiving SDK analgesia. Primary data analyses included type of SDK
      administration (intravenous push [IVP], short-infusion [SI] or continuous
      infusion [CI]), dosing, rates of analgesic utilization before and after SDK
      administration, and adverse effects. RESULTS: Three hundred sixty-two patients
      were enrolled in the study. Mean ketamine doses given by IVP, SI and CI were 26.3
      mg, 23.4 mg, and 11.3 mg. The mean duration of CI was 135.87 minutes. The
      percentage of patients not requiring post-SDK analgesia increased by 16%, 18%,
      and 37% in IVP, SI and CI groups. Adverse effects were recorded for 13% of
      patients. CONCLUSION: SDK administered by IVP, SI, and CI in the ED for a variety
      of painful conditions is a feasible analgesic modality in the ED that is
      associated with a decrease in overall requirements of post-ketamine analgesia and
      opioid sparing.

PMID- 30181789
TI  - Structure of graphene and its disorders: a review.
AB  - Monolayer graphene exhibits extraordinary properties owing to the unique, regular
      arrangement of atoms in it. However, graphene is usually modified for specific
      applications, which introduces disorder. This article presents details of
      graphene structure, including sp2 hybridization, critical parameters of the unit
      cell, formation of sigma and pi bonds, electronic band structure, edge
      orientations, and the number and stacking order of graphene layers. We also
      discuss topics related to the creation and configuration of disorders in
      graphene, such as corrugations, topological defects, vacancies, adatoms and sp3
      defects. The effects of these disorders on the electrical, thermal, chemical and
      mechanical properties of graphene are analyzed subsequently. Finally, we review
      previous work on the modulation of structural defects in graphene for specific
      applications.

PMID- 30181792
TI  - Effect of sedative agent selection on morbidity, mortality and length of stay in
      patients with increase in intracranial pressure.
AB  - BACKGROUND: To identify the effects of sedative agent selection on morbidity,
      mortality, and length of stay in patients with suspected increase in intracranial
      pressure. Recent trends and developments have resulted in changes to medications
      that were previously utilized as pharmacological adjuncts in the sedation and
      intubation of patients with suspected increases in intracranial pressure.
      Medications that were previously considered contraindicated are now being used
      with increasing regularity without demonstrated safety and effectiveness. The
      primary objective of this study is to evaluate and compare the use of Ketamine as
      an induction agent for patients with increased intracranial pressure. The
      secondary objective was to evaluate and compare the use of Etomidate, Midazolam,
      and Ketamine in patients with increased intracranial pressure. METHODS: We
      conducted a retrospective chart review of patients transported to our facility
      with evidence of intracranial hypertension that were intubated before trauma
      center arrival. Patients were identified during a 22-month period from January
      2014 to October 2015. Goals were to evaluate the impact of sedative agent
      selection on morbidity, mortality, and length of stay. RESULTS: During the review
      148 patients were identified as meeting inclusion criteria, 52 were excluded due
      to incomplete data. Of those the patients primarily received; Etomidate,
      Ketamine, and Midazolam. Patients in the Ketamine group were found to have a
      lower mortality rate after injury stratification. CONCLUSION: Patients with
      intracranial hypertension should not be excluded from receiving Ketamine during
      intubation out of concern for worsening outcomes.

PMID- 30181793
TI  - Utility of point-of-care musculoskeletal ultrasound in the evaluation of
      emergency department musculoskeletal pathology.
AB  - BACKGROUND: To evaluate the utilization of point-of-care ultrasound (POCUS) for
      the assessment of emergency department (ED) patients with musculoskeletal
      symptoms and the impact of musculoskeletal POCUS on medical decision-making and
      patient management in the ED. METHODS: This was a retrospective review of ED
      patients presenting with musculoskeletal symptoms who received a POCUS over a 3.5
      year period. An ED POCUS database was reviewed for musculoskeletal POCUS
      examinations used for medical decision-making. Electronic medical records were
      then reviewed for demographic characteristics, history, physical examination
      findings, ED course, additional imaging studies, and impact of musculoskeletal
      POCUS on patient management in ED. RESULTS: A total of 264 subjects (92 females,
      172 males) and 292 musculoskeletal POCUS examinations were included in the final
      analysis. Most common symptomatic sites were knee (31.8%) and ankle (16.3%).
      Joint effusion was the most common finding on musculoskeletal POCUS, noted in
      33.7% of the patients, and subcutaneous edema/cobblestoning was found in 10.2% of
      the patients. Muscle or tendon rupture was found in 2.3% of the patients, and
      1.9% of the patients had joint dislocation. Bursitis or bursa fluid was found in
      3.4% of patients, and tendonitis/tendinopathy was found in 2.3%. Twenty percent
      of them were ultrasound-guided musculoskeletal procedures, and most of them
      (73.3%) were arthrocentesis. Of the included studies, all except three either
      changed or helped guide patient management as documented in the patients' medical
      records. CONCLUSION: Our study findings illustrate the utility of POCUS in the
      evaluation of a variety of musculoskeletal pathologies in the ED.

PMID- 30181794
TI  - Accuracy of abdominal ultrasound for the diagnosis of small bowel obstruction in
      the emergency department.
AB  - BACKGROUND: Emergency physicians frequently encounter patients with acute small
      bowel obstructions (SBO). Although computed tomography (CT) imaging is the
      current gold standard in the assessment of patients with suspected SBO in the
      emergency department, a few studies have examined the use of ultrasound as an
      alternative imaging technique. METHODS: We evaluated the accuracy of ultrasound
      performed in the ED by a variety of providers (physicians with various levels of
      training, physician assistants) compared to CT imaging in 47 patients with
      suspected SBOs. RESULTS: Our data demonstrated a sensitivity of 93.8% and a
      specificity of 93.3% when compared to abdominal CT, and a sensitivity of 94.3%
      and specificity of 95.2% using a composite endpoint of abdominal CT and discharge
      diagnosis. CONCLUSION: Ultrasound can play an important role in the
      identification of small bowel obstructions in ED patients.

PMID- 30181795
TI  - Ultrasonographic assessment of paediatric ocular emergencies: A tertiary eye
      hospital based observation.
AB  - BACKGROUND: The purpose of this study is to assess the utility of ocular
      ultrasound B scan in the emergency at the first point of care for detecting
      posterior segment and orbital pathologies in cases of paediatric ocular
      emergencies. METHODS: A prospective observational study involving 122 paediatric
      patients presenting to eye emergency over a period of ninety days were assessed
      with ultrasonography for the posterior segment as well as orbital pathology
      whenever indicated. The ocular ultrasound was performed gently over closed
      eyelids. RESULTS: Posttraumatic globe injuries were the most common indication
      for posterior segment evaluation, which constituted 80 (65.57%) eyes. Among these
      52 patients had an anechoic posterior segment and 28 patients had variable
      findings such as vitreous haemorrhage (8.19%), retinal detachment (6.55%),
      choroidal detachment (4.91%), posteriorly dislocated clear lens (0.81%) and
      retained intraocular foreign body (5.73%). Non-traumatic cases constituted around
      42 (34.42%) eyes, which included corneal ulcer (7.37%), retinoblastoma (6.55%),
      endophthalmitis (4.91%), extra-ocular muscle cysticercosis (4.91%), orbital
      cellulitis (4.09%), periocular haemorrhage (2.45%), proptosis(1.63%), paediatric
      cataract (1.63%) and cryptophthalmos (0.81%). No adverse events of performing the
      ultrasound was noted. CONCLUSION: First point ultrasonography in paediatric
      ocular emergencies is a cheap, portable and an effective tool in the assertion of
      significant posterior segment and orbital diseases.

PMID- 30181796
TI  - Estimating the weight of children in Nepal by Broselow, PAWPER XL and Mercy
      method.
AB  - BACKGROUND: Resuscitation of a critically-ill child requires an accurate weight
      for fluids and medication dosing; however, weighing children on a scale while
      critically ill is not always practical. The objective of this study is to
      determine the accuracy of three different weight estimation methods (Broselow,
      PAWPER XL and Mercy tape) of children presenting to Patan Hospital, Nepal.
      METHODS: This was a prospective, cross-sectional study that included children
      presenting to the emergency department and under-fourteen outpatient clinic at
      Patan Hospital. Measured weight was compared to estimated weight of Broselow,
      PAWPER XL, and Mercy tapes. The mean percentage error and percentage of estimated
      weights that were within 10% (PW10) and 20% (PW20) of actual weight were
      calculated. Acceptable accuracy was determined as a PW10>70% and PW20>95%. A
      Bland-Altman analysis was done to determine agreement between each weight
      estimation method and actual weight. RESULTS: The study included 813 children.
      The mean age was 4.2 years (ranging from 4 days to 14 years) with 60% male. The
      mean percentage error (MPE) for Broselow, PAWPER XL and Mercy were -1.0% (SD
      11.8), 0.7% (10.5) and 4.2% (11.9) respectively. The predicted weight within 10%
      was highest for the PAWPER XL (71.5%) followed by Broselow (63.2%) and Mercy
      (58.1%). The predicted weight within 20% of actual weight was 95.2%, 91.5% and
      91.3% for PAWPER XL, Broselow and Mercy respectively. CONCLUSION: The PAWPER XL
      tape was the only method found to be accurate in estimating the weight of
      Nepalese children.

PMID- 30181797
TI  - Comparison of exogenous melatonin versus placebo on sleep efficiency in emergency
      medicine residents working night shifts: A randomized trial.
AB  - BACKGROUND: Sleep deprivation resulting from night shifts, is a major cause of
      burnout among physicians. Exogenous melatonin may improve sleep quality in night
      shift workers. The study aims to compare the effectiveness of melatonin versus
      placebo on sleep efficiency in emergency medicine (EM) residents. METHODS: A
      randomized, double-blind, replicated crossover trial was performed on EM
      residents. This study consisted of 4 phases within a month with intervention
      periods of 2 nights and washouts of 6 days. In our study, EM residents had nine
      hour shifts on 6 consecutive days, 2 mornings, 2 evenings and 2 nights and then 2
      days off. At the end of shifts' cycle, 24 EM residents were given 3 mg melatonin
      or placebo (12 in each arm of the study) for 2 consecutive nights after the
      second night shift with crossover to the other arm after a six-day off drug. This
      crossover intervention was repeated for two more another time. Finally, we
      created 48 cases and comparisons in each arm. Different items related to sleep
      quality were assessed and compared both within the same group and between the two
      groups. RESULTS: In the melatonin group, daytime sleepiness (calculated by
      Karolinska Sleep Scale) had a significant reduction after taking the second dose
      of drug (P=0.003) but the same result was not observed when comparing the 2
      groups. Mood status (calculated by Profile of Mood States) showed no remarkable
      difference between the 2 groups. CONCLUSION: Melatonin might have a limited
      benefit on sleep quality in EM residents working night shifts.

PMID- 30181798
TI  - A case of thyroid emergency with cardiac arrest supported by extracorporeal
      membrane oxygenation.

PMID- 30181799
TI  - Emergency department diagnosis of an ovarian inguinal hernia in an 11-year-old
      female using point-of-care ultrasound.

PMID- 30181800
TI  - A rare cause of foot drop: Tired bullet.

PMID- 30181801
TI  - Itaconic acid indicates cellular but not systemic immune system activation.
AB  - Itaconic acid is produced by mammalian leukocytes upon pro-inflammatory
      activation. It appears to inhibit bacterial growth and to rewire the metabolism
      of the host cell by inhibiting succinate dehydrogenase. Yet, it is unknown
      whether itaconic acid acts only intracellularly, locally in a paracrine fashion,
      or whether it is even secreted from the inflammatory cells at meaningful levels
      in peripheral blood of patients with severe inflammation or sepsis. The aim of
      this study was to determine the release rate of itaconic acid from pro
      inflammatory activated macrophages in vitro and to test for the abundance of
      itaconic acid in bodyfluids of patients suffering from acute inflammation. We
      demonstrate that excretion of itaconic acid happens at a low rate and that it
      cannot be detected in significant amounts in plasma or urine of septic patients
      or in liquid from bronchial lavage of patients with pulmonary inflammation. We
      conclude that itaconic acid may serve as a pro-inflammatory marker in immune
      cells but that it does not qualify as a biomarker in the tested body fluids.

PMID- 30181802
TI  - A nomogram prediction for the survival of patients with triple negative breast
      cancer.
AB  - Triple negative breast cancer (TNBC) is a subtype of breast cancer with poor
      prognosis. In this study, we aimed to conduct a nomogram to predict the survival
      of individual with TNBC by incorporating significant clinical and laboratory
      parameters. 404 TNBC patients from the Affiliated Union Hospital of Fujian
      Medical University between 2006 and 2012 were selected in the training cohort.
      Cox univariate and multivariate regression analyses were adopted to identify
      independent prognostic factors. The predictive accuracy and discriminative
      ability of this nomogram were evaluated by concordance index (C-index) and
      calibration curve. The accuracy of this nomogram was also compared with the 8th
      AJCC TNM staging system. An external validation cohort was further performed in
      an independent cohort of 200 patients between 2012 and 2014. Seven independent
      prognostic factors, including family history of breast cancer, tumor location,
      number of positive lymph nodes, histological grade, serum CEA, CA125 and CA153
      were identified as independent prognostic factors. A nomogram incorporating these
      prognostic factors was subsequently conducted and the calibration plot on the
      probability for 3 or 5 years overall survival (OS) showed an optimal agreement
      between the nomogram prediction and actual observations. In addition, the C-index
      of this nomogram was higher than that of TNM staging system in both training and
      validation cohort (training cohort, 0.76 vs. 0.66, p<0.001 and validation cohort,
      0.72 vs. 0.64, p=0.002, respectively). This proposed nomogram could provide more
      accurate individual prediction for the prognosis of the patients with TNBC and
      was able to help physicians to identify subgroups of patients at different risk
      and to decide who need intensive follow-up or additional treatment.

PMID- 30181803
TI  - Discovery of DEBIC to correlate P-selectin inhibition and DNA intercalation in
      cancer therapy and complicated thrombosis.
AB  - Arterial thrombosis is one of the major complications of cancer and can seriously
      worsen the prognosis of the patients. These clinical findings encouraged this
      paper to correlate P-selectin inhibition and DNA intercalation in cancer therapy
      and complicated thrombosis. By designing and docking 12 derivatives of bisindole-
      2-carboxylic acids into the active sites of P-selectin and d(CGATCG)2 9
      derivatives were assigned to receive in vivo anti-tumor assay, and finally
      provided dimethyl 2,2'-[(2,2'-(ethane-1,1-diyl)bis(1H-indole-3,2-diyl)]diacetate
      (DEBIC) to receive assays. DEBIC intercalated DNA and inhibited proliferation of
      tumor cells but not non-tumor cells. It slowed tumor growth of S180 mice at a
      dose of 0.36 MUmol/kg, and slowed tumor growth of A549 bearing BABL/C mice at a
      dose of 8.9 MUmol/kg. DEBIC was also found to inhibit arterial thrombosis by down
      regulating P-selectin effectively at a dose of 0.36 MUmol/kg.

PMID- 30181804
TI  - Pumilio2 regulates synaptic plasticity via translational repression of synaptic
      receptors in mice.
AB  - PUMILIO 2 (PUM2) is a member of Pumilio and FBF (PUF) family, an RNA binding
      protein family with phylogenetically conserved roles in germ cell development.
      The Drosophila Pumilio homolog is also required for dendrite morphogenesis and
      synaptic function via translational control of synaptic proteins, such as
      glutamate receptors, and recent mammalian studies demonstrated a similar role in
      neuronal culture with associated motor and memory abnormalities in vivo.
      Importantly, transgenic mice with PUM2 knockout show prominent epileptiform
      activity, and patients with intractable temporal lobe epilepsy and mice with
      pilocarpine-induced seizures have decreased neuronal PUM2, possibly leading to
      further seizure susceptibility. However, how PUM2 influences synaptic function in
      vivo and, subsequently, seizures is not known. We found that PUM2 is highly
      expressed in the brain, especially in the temporal lobe, and knockout of Pum2
      (Pum2-/- ) resulted in significantly increased pyramidal cell dendrite spine and
      synapse density. In addition, multiple proteins associated with excitatory
      synaptic function, including glutamate receptor 2 (GLUR2), are up-regulated in
      Pum2-/- mice. The expression of GLUR2 protein but not mRNA is increased in the
      Pum2-/- mutant hippocampus, Glur2 transcripts are increased in mutant polysome
      fractions, and overexpression of PUM2 led to repression of reporter expression
      containing the 3'Untranslated Region (3'UTR) of Glur2, suggesting translation of
      GLUR2 was increased in the absence of Pum2. Overall, these studies provide a
      molecular mechanism for the increased temporal lobe excitability observed with
      PUM2 loss and suggest PUM2 might contribute to intractable temporal lobe
      epilepsy.

PMID- 30181805
TI  - Identification of key pathways and genes in response to trastuzumab treatment in
      breast cancer using bioinformatics analysis.
AB  - Breast cancer (BC) is one of the leading causes of death among women worldwide.
      The gene expression profile GSE22358 was downloaded from the Gene Expression
      Omnibus (GEO) database, which included 154 operable early-stage breast cancer
      samples treated with neoadjuvant capecitabine plus docetaxel, with (34) or
      without trastuzumab (120), to identify gene signatures during trastuzumab
      treatment and uncover their potential mechanisms. The gene ontology (GO) and
      Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were
      performed, and a protein-protein interaction (PPI) network of the differentially
      expressed genes (DEGs) was constructed by Cytoscape software. There were 2284
      DEGs, including 1231 up-regulated genes enriched in DNA replication, protein N
      linked glycosylation via asparagine, and response to toxic substances, while 1053
      down-regulated genes were enriched in axon guidance, protein localization to
      plasma membrane, protein stabilization, and protein glycosylation. Eight hub
      genes were identified from the PPI network, including GSK3B, RAC1, PXN, ERBB2,
      HSP90AA1, FGF2, PIK3R1 and RAC2. Our experimental results showed that GSK3B was
      also highly expressed in breast cancer tissues and was associated with poor
      survival, as was beta-catenin. In conclusion, the present study indicated that
      the identified DEGs and hub genes further our understanding of the molecular
      mechanisms underlying trastuzumab treatment in BC and highlighted GSK3B, which
      might be used as a molecular target for the treatment of BC.

PMID- 30181806
TI  - Somatic genome alterations in relation to age in lung squamous cell carcinoma.
AB  - Lung squamous cell carcinoma (LUSC) is the most common cause of global cancer
      related mortality and the major risk factors is smoking consumption. By analyzing
      ~500 LUSC samples from The Cancer Genome Atlas, we detected a higher mutational
      burden as well as a higher level of methylation changes in younger patients. The
      SNPs mutational profiling showed enrichments of smoking-related signature 4 and
      defective DNA mismatch repair (MMR)-related signature 6 in younger patients,
      while the defective DNA MMR signature 26 was enriched among older patients.
      Furthermore, gene set enrichment analysis was performed in order to explore
      functional effect of somatic alterations in relation to patient age.
      Extracellular Matrix-Receptor Interaction, Nucleotide Excision Repair and Axon
      Guidance seem crucial disrupted pathways in younger patients. We hypothesize that
      a higher sensitivity to smoking-related damages and the enrichment of defective
      DNA MMR related mutations may contribute to the higher mutational burden of
      younger patients. The two distinct age-related defective DNA MMR signatures 6 and
      26 might be crucial mutational patterns in LUSC tumorigenesis which may develop
      distinct phenotypes. Our study provides indications of age-dependent differences
      in mutational backgrounds (SNPs and CNVs) as well as epigenetic patterns that
      might be relevant for age adjusted treatment approaches.

PMID- 30181807
TI  - Metastases risk in thin cutaneous melanoma: prognostic value of clinical
      pathologic characteristics and mutation profile.
AB  - Background: A high percentage of patients with thin melanoma (TM), defined as
      lesions with Breslow thickness <=1 mm, presents excellent long-term survival,
      however, some patients develop metastases. Existing prognostic factors cannot
      reliably differentiate TM patients at risk for metastases. Objective: We aimed at
      characterizing the clinical-pathologic and mutation profile of metastatic and not
      metastatic TM in order to distinguish lesions at risk of metastases. Methods:
      Clinical-pathologic characteristics were recorded for the TM cases analyzed. We
      used a Next Generation Sequencing (NGS) multi-gene panel to characterize TM for
      multiple somatic mutations. Results: A statistically significant association
      emerged between the presence of metastases and Breslow thickness >=0.6 mm
      (p=0.003). None of TM with lymph-node involvement had Breslow thickness <0.6 mm.
      Somatic mutations were identified in 19 of 21 TM analyzed (90.5%). No mutations
      were observed in two not-metastatic cases with the lowest Breslow thickness
      (<=0.4 mm), whereas mutations in more than one gene were detected in one
      metastatic case with the highest Breslow thickness (1.00 mm). Conclusion: Our
      study indicates Breslow thickness >=0.6 mm as a valid prognostic factor to
      distinguish TM at risk for metastases.

PMID- 30181808
TI  - Sonoporation by microbubbles as gene therapy approach against liver cancer.
AB  - Introduction: An innovative method, known as sonoporation, was used to induce the
      expression of silenced genes, such as (but not restricted to) TRAIL and p53, in
      liver cancer cells (HepG2). The principal aim of the present study was the re
      activation of silenced apoptotic pathways in liver cancer models, by using
      diagnostic synovial microbubble as plasmid gene delivery tools in combination
      with epigenetic treatments. Material and methods: HepG2 cells were used as a
      liver cancer model. Microbubbles (Sonovue(r)) were chosen as gene deliver system
      in combination with the sonoporation approach. Plasmid pEGFP-TRAIL and pEGFP-p53
      were selected and propagated in Escherichia coli grown in LB broth, in order to
      obtain the necessary amount. Results: Sonoporation was induced by using
      transducer (Sonitron 2000) and, among the several conditions tested, 3 MHz, 51%
      Duty Cycle, and 5 W/cm2, 30 s resulted as the best parameters. Data collected
      showed a dose dependent effect in terms of output energy. A transfection efficacy
      of 30 - 50% was achieved and recombinant gene expression induced apoptotic
      effects. In order to increase efficacy, we used the histone deacetylase inhibitor
      (HDACi, entinostat) MS-275, able to activate TRAIL and thus inducing a stronger
      pro-apoptotic effect in combination with TRAIL-gene re-expression. Conclusion:
      For the first time, it was shown the possibility to induce the exogenous
      expression of the pro-apoptotic gene TRAIL and p53 in a liver cancer HepG2 cells
      via a sonoporation procedure. The epigenetic treatment using HDACi was able to
      increase the pro-apoptotic effects of the gene therapy.

PMID- 30181809
TI  - 3D hydrogel breast cancer models for studying the effects of hypoxia on
      epithelial to mesenchymal transition.
AB  - Solid tumors are 3D assemblies of cancer cells, together with multiple stromal
      cell types within an extracellular matrix. Yet, the vast majority of cell-based
      studies to characterize oncogenesis and discovery of new anti-cancer drugs is
      conducted using conventional 2D monolayer culture systems, where cells are grown
      on plastic substratum under normoxic environments. In current study, we generated
      3D breast cancer cell culture platform consists of photocrosslinkable hydrogels
      and encapsulated isogenic primary (21PT) and a metastatic (21MT-2) breast cancer
      cell lines derived from the primary tumor and pleural effusion from the same
      patient. We demonstrated that hypoxia decreased cellular assembly size and
      density, and promoted epithelial to mesenchymal transition (EMT) process, without
      affecting cell viability. Next, we showed hypoxia enhanced breast cancer cell
      migration, and expression and secretion of lysyl oxidase (LOX), which is copper
      dependent amine oxidase and has the primary function to drive the crosslinking of
      collagen and elastin and is regulated by hypoxia. Furthermore, to recapitulate in
      vivo situation, we generated breast cancer and lung cells (derived from the same
      patient) contact model by stacking 3D hydrogel constructs with breast cancer
      cells onto lung mesenchymal cells (LMC) laden-hydrogel and then showed breast
      cancer cells migrated towards LMC during hypoxia. Lastly, as a validation of this
      model for future screen of therapeutic agents, we demonstrated that LOX inhibitor
      exhibited a significant decrease in breast cancer cell viability, migration, and
      EMT. Taken together, these results validate the use of hydrogels based models to
      examine hypoxia related EMT in breast cancer cells.

PMID- 30181810
TI  - FGFR3 mRNA overexpression defines a subset of oligometastatic colorectal cancers
      with worse prognosis.
AB  - Objectives: Metastatic colorectal cancer (CRC) remains a leading cause of cancer
      related deaths. Patients with oligometastatic liver disease represent a clinical
      subgroup with heterogeneous course. Until now, biomarkers to characterize outcome
      and therapeutic options have not been fully established. Methods: We investigated
      the prevalence of FGFR alterations in a total of 140 primary colorectal tumors
      and 63 liver metastases of 55 oligometastatic CRC patients. FGF receptors (FGFR1
      4) and their ligands (FGF3, 4 and 19) were analyzed for gene amplifications and
      rearrangements as well as for RNA overexpression in situ. Results were correlated
      with clinico-pathologic data and molecular subtypes. Results: Primary tumors
      showed FGFR1 (6.3%) and FGF3,4,19 (2.2%) amplifications as well as FGFR1 (10.1%),
      FGFR2 (5.5%) and FGFR3 (16.2%) overexpression. In metastases, we observed FGFR1
      amplifications (4.8%) as well as FGFR1 (8.5%) and FGFR3 (14.9%) overexpression.
      Neither FGFR2-4 amplifications nor gene rearrangements were observed. FGFR3
      overexpression was significantly associated with shorter overall survival in
      metastases (mOS 19.9 vs. 47.4 months, HR=3.14, p=0.0152), but not in primary CRC
      (HR=1.01, p=0.985). Although rare, also FGFR1 amplification was indicative of
      worse outcome (mOS 12.6 vs. 47.4 months, HR=8.83, p=0.00111). Conclusions: We
      provide the so far most comprehensive analysis of FGFR alterations in primary and
      metastatic CRC. We describe FGFR3 overexpression in 15% of CRC patients with
      oligometastatic liver disease as a prognosticator for poor outcome. Recently
      FGFR3 overexpression has been shown to be a potential therapeutic target.
      Therefore, we suggest focusing on this subgroup in upcoming clinical trials with
      FGFR-targeted therapies.

PMID- 30181811
TI  - Abnormal regulation of BCR signalling by c-Cbl in chronic lymphocytic leukaemia.
AB  - Abnormalities of molecules involved in signal transduction pathways are connected
      to Chronic Lymphocytic Leukemia (CLL) pathogenesis and a critical role has been
      already ascribed to B-Cell Receptor (BCR)-Lyn axis. E3 ubiquitin ligase c-Cbl,
      working together with adapter protein CIN85, controls the degradation of protein
      kinases involved in BCR signaling. To investigate cell homeostasis in CLL, we
      studied c-Cbl since in normal B cells it is involved in the ubiquitin-dependent
      Lyn degradation and in the down-regulation of BCR signaling. We found that c-Cbl
      is overexpressed and not ubiquitinated after BCR engagement. We observed that c
      Cbl did not associate to CIN85 in CLL with respect to normal B cells at steady
      state, nor following BCR engagement. c-Cbl association to Lyn was not detectable
      in CLL after BCR stimulation, as it happens in normal B cells. In some CLL
      patients, c-Cbl is constitutively phosphorylated at Y731 and in the same
      subjects, it associated to regulatory subunit p85 of PI3K. Moreover, c-Cbl is
      constitutive associated to Cortactin in those CLL patients presenting Cortactin
      overexpression and bad prognosis. These results support the hypothesis that c
      Cbl, rather than E3 ligase activity, could have an adaptor function in turn
      influencing cell homeostasis in CLL.

PMID- 30181812
TI  - Accelerated BRAF mutation analysis using a fully automated PCR platform improves
      the management of patients with metastatic melanoma.
AB  - Background: Determination of BRAF status is important for the therapeutic
      management of patients with metastatic melanoma. Objectives: We evaluated the
      impact of a faster determination of BRAF mutational status on the delay between
      initial consultation and initiation of treatment. Results: For the FA-PCR group a
      median delay of 16 days [11;18] was observed between initial consultation and the
      implementation of treatment, which was significantly lower than that observed for
      the SOP group (26 days [20;46], p = 0.035). Conclusions: In comparison to using
      conventional SOP, using an FA-PCR platform for BRAF mutation analysis of patients
      with metastatic melanoma significantly reduced the delay in initiation of
      personalized therapy by 10 days. Materials and Methods: Analysis of the BRAF
      mutation status of eight formalin-fixed paraffin-embedded (FFPE) tissue samples
      was performed using a CE-IVD fully-automated (FA) PCR-based platform. The delay
      between initial consultation and the implementation of treatment was compared
      between these samples (FA-PCR group) and a retrospective group of 29 FFPE samples
      analysed by standard operating procedures (SOP group) using conventional PCR.

PMID- 30181813
TI  - Prognostic significance of six clinicopathological features for biochemical
      recurrence after radical prostatectomy: a systematic review and meta-analysis.
AB  - Identifying patients with high risk of biochemical recurrence after radical
      prostatectomy is of immense value in clinical practice. Assessment of prognostic
      significance of specific clinicopathological features plays an important role in
      surgical management after prostatectomy. The purpose of our meta-analysis was to
      investigate the association between the six pathological characteristics and the
      prognosis of prostate cancer. We carried out a systematic document retrieval in
      electronic databases to sort out appropriate studies. Outcomes of interest were
      gathered from studies comparing biochemical recurrence-free survival (BCFS) in
      patients with the six pathological traits. Studies results were pooled, and
      hazard ratios (HRs) combined with corresponding 95% confidence intervals (CIs)
      for survival were used to estimate the effect size. 29 studies (21,683 patients)
      were enrolled in our meta-analysis. All the six predictors were statistically
      significant for BCFS with regard to seminal vesicle invasion (HR = 1.97, 95% CI =
      1.79-2.18, p < 0.00001), positive surgical margin (HR = 1.79, 95% CI = 1.56-2.06,
      p < 0.00001), extracapsular extension (HR = 2.03, 95% CI = 1.65-2.50, p <
      0.0001), lymphovascular invasion (HR = 1.85, 95% CI = 1.54-2.22, p < 0.00001),
      lymph node involvement (HR = 1.88, 95% CI = 1.37-2.60, p = 0.0001) and perineural
      invasion (HR = 1.59, 95% CI = 1.33-1.91, p < 0.00001). Subgroup analysis showed
      that all the six predictors had significantly relationship with poor BCFS. The
      pooled results demonstrated that the six clinical findings indicated a worse
      prognosis in patients with prostate cancer. In conclusion, our results show
      several clinicopathological characteristics can predict the risk of biochemical
      recurrence after radical prostatectomy. Prospective studies are needed to further
      confirm the predictive value of these features for the prognosis of prostate
      cancer patients after radical prostatectomy.

PMID- 30181814
TI  - No associations between fruit and vegetable consumption and pancreatic cancer
      risk: a meta-analysis of prospective studies.
AB  - The associations between fruit and vegetable consumption and pancreatic cancer
      risk are inconclusive. We conducted a meta-analysis of prospective studies to
      investigate the associations. The search was conducted systemically using the
      PubMed and EMBASE databases up to March 2017. Relative risks and 95% confidence
      intervals for the highest versus lowest consumption and dose-response analyses
      were assessed. Subtype and subgroup analyses were performed. Twelve studies were
      eligible. The summary relative risks of the highest versus lowest consumption
      were 0.95 (0.80-1.12) for total fruits and vegetables without heterogeneity (I2 =
      0%, P = 0.44), 0.96 (0.82-1.12) for fruits without low heterogeneity (I2 = 37%, P
      = 0.12) and 0.94 (0.84-1.06) for vegetables with low heterogeneity (I2 = 9%, P=
      0.36). Dose-response analyses also showed no significantly inverse associations
      for each 100 g/day increase; the summary relative risks were 1.00 (0.98-1.02) for
      total fruits and vegetables, 1.01 (0.97-1.05) for fruits and 1.00 (0.97-1.03) for
      vegetables. The results of subtype analyses were consistent with the fruit and
      vegetable analyses; the relative risks were 0.97 (0.80-1.17) for citrus fruit
      without low heterogeneity (I2 = 39%, P = 0.15) and 0.89 (0.76-1.05) for
      cruciferous vegetables without low heterogeneity (I2 = 14%, P= 0.32). In
      conclusion, this meta-analysis does not support significant associations between
      fruit and vegetable consumption and pancreatic cancer risk.

PMID- 30181815
TI  - Treatment-related toxicities of apatinib in solid tumors: a meta-analysis.
AB  - Background: Apatinib is a novel small molecular drug targeting vascular
      endothelial growth factor receptor-2 (VEGFR-2), which is being studied in
      multiple tumor types. We performed a meta-analysis to quantify the overall
      incidence and risk of hypertension, proteinuria, and hand-foot-syndrome (HFS) in
      cancer patients receiving apatinib. Results: Altogether, 820 cancer patients from
      7 prospective trials were included for the meta-analysis. The incidences of all
      grade and high-grade hypertension were 45.4% and 9.7%. The incidences of all
      grade and high-grade proteinuria were 45.1% and 3.7%. The incidences of all-grade
      and high-grade HFS were 35.9% and 8.6%. The RRs of all-grade hypertension,
      proteinuria and HFS of apatinib compared to placebo were increased (hypertension,
      RR = 6.53; proteinuria, RR = 2.62, and HFS, RR = 11.45). The RRs of developing
      high-grade hypertension and HFS were substantially higher than that of placebo
      (hypertension, RR = 7.73; HFS, RR = 7.23), but not for proteinuria (RR = 2.56,
      95% CI: 0.57-11.52). Materials and Methods: Prospective phase II and III clinical
      trials of cancer patients receiving apatinib were searched and included. Summary
      incidences, relative risk (RR), and 95% confidence intervals (CI) were calculated
      by using either fixed or random effects models according to the heterogeneity of
      the studies. Conclusions: Apatinib is generally well tolerated, and associated
      with increased risks of all-grade hypertension, proteinuria and HFS, and high
      grade hypertension and HFS, but not high-grade proteinuria.

PMID- 30181816
TI  - Correction: Immunogenicity of mammary tumor cells can be induced by shikonin via
      direct binding-interference with hnRNPA1.
AB  - [This corrects the article DOI: 10.18632/oncotarget.9660.].

PMID- 30181817
TI  - Correction: CM363, a novel naphthoquinone derivative which acts as multikinase
      modulator and overcomes imatinib resistance in chronic myelogenous leukemia.
AB  - [This corrects the article DOI: 10.18632/oncotarget.11425.].

PMID- 30181818
TI  - Correction: Systematic review and meta-analysis comparing zoledronic acid
      administered at 12-week and 4-week intervals in patients with bone metastasis.
AB  - [This corrects the article DOI: 10.18632/oncotarget.19856.].

PMID- 30181819
TI  - In situ substrate-formed biofilms using IDODS mimic supragingival tooth-formed
      biofilms.
AB  - This study aimed to compare the bacterial viability and diversity of a substrate
      formed biofilm (SF-biofilm) in situ to a supragingival tooth-formed biofilm (TF
      biofilm) in the same group of individuals. The impact of the device/disc position
      and toothbrushing during the formation of SF-biofilm was also assessed. Two tests
      were run. In test 1, 15 volunteers wore two hemi-splints carrying six discs of
      human enamel, glass, and hydroxyapatite for 2 days, and were instructed to not
      perform any oral hygiene measure. Biofilm samples were collected from the
      substrates and the contralateral tooth and were analysed using CLSM. In five
      volunteers, half of the biofilm present on the discs and their contralateral
      teeth were scraped and analysed using 16S  pyrosequencing. In test 2, the
      microscopic analysis was repeated only on the SF-biofilm samples, and the
      volunteers were allowed to brush their teeth. Multivariate analyses revealed that
      the donors had a significant effect on the composition of the biofilm, confirming
      its subject-dependent character. The bacterial composition of the SF-biofilm was
      similar to the TF-biofilm, with significant differential abundance detected in
      very few taxa of low abundance. The toothbrushing during the formation of SF
      biofilm was the only factor that conditioned the thickness or bacterial
      viability.

PMID- 30181820
TI  - Internal medicine fellowship directors' perspectives on the quality and utility
      of letters conforming to residency program director letter of recommendation
      guidelines.
AB  - Background: In May 2017, the Alliance for Academic Internal Medicine (AAIM)
      published guidelines intending to standardize and improve internal medicine
      residency program director (PD) letters of recommendation (LORs) for fellowship
      applicants. Objectives: This study aimed to examine fellowship PDs impressions of
      the new guidelines, letter writers' adherence to the guidelines, and the impact
      of LORs that conformed to guidelines compared to non-standardized letters.
      Methods: The authors anonymously surveyed fellowship PDs from January to March
      2018 to gather input about LORs submitted to their programs during the 2017
      fellowship application cycle. Results: A total of 78% of survey respondents were
      satisfied with letters that followed the AAIM guidelines, whereas 48% of
      respondents were satisfied with letters that did not. Fellowship PDs felt that
      letters that followed the AAIM guidelines were more helpful than letters that did
      not, especially for differentiating between applicants from the same institution
      and for understanding residents' performance across the six core competency
      domains. Fellowship PDs provided several suggestions for residency PDs to make
      the LORs even more helpful. Conclusion: Fellowship PD respondents indicated that
      LORs that followed the new AAIM guidelines were more helpful than letters that
      did not.

PMID- 30181821
TI  - Promoting scholarship in a community-based internal medicine residency.
AB  - The University of South Dakota Sanford School of Medicine Internal Medicine
      residency implemented a program to enhance scholarship among residents. This
      residency is part of a small Mid-Western community-based school. Background: A
      Director of Research was hired and developed a structured approach consisting of:
      1. Independent study regarding research methods and statistical testing and 2.
      Mentoring of residents and faculty in scholarly pursuits starting in the first
      months of residency. Methods: Scholarship for two cohorts of residents for years
      July 2011-2014 and January 2014-2017 were followed. Products included papers
      accepted/published and papers accepted/presented at national or international
      meetings. Results: 7 (14.8%) of 47 residents in the first cohort published 12
      papers (0.25 papers/resident) with 18 faculty as co-authors (1.5/paper). 20
      (43.4%) of 46 residents in the second cohort (structured program) published 39
      papers (0.85 papers/resident) with 80 faculty as co-authors (2.1/paper). The
      difference in papers was significant by chi-square analysis. Conclusion: A
      structured program requiring independent study in conjunction with individualized
      mentoring of scholarship starting early in the first postgraduate year was
      successful in significantly increasing the scholarly activity of our community
      based internal medicine residents and faculty. With this program, the percentage
      of residents publishing exceeds national statistics recently reported.

PMID- 30181823
TI  - Maryland ACP Mulholland Mohler winning resident abstracts 2018.
AB  - 2018 Winners at the Maryland Chapter, ACP Mulholland Mohler Residents Meeting.

PMID- 30181822
TI  - A quality improvement intervention to enhance performance and perceived
      confidence of new internal medicine residents.
AB  - Background: Orientation for new medical residents is challenging due to the
      diversity of prior experiences and cultural backgrounds and is compounded by a
      lack of orientation curricula that adequately addresses the needs of the medical
      residents to allow them to perform their duties in an efficient manner from the
      start. The beginning of residency training is associated with reduced quality of
      healthcare widely referred to as the 'July effect'. Objective: To assess the
      impact of a peer-led orientation for new interns on (a) self-reported confidence
      level, (b) improvement in performance of first-year residents in appropriate
      clinical documentation and efficient discharge procedures and protocols.
      Design/methods: In June 2016, a hybrid of interactive teaching and simulation
      exercises was used to teach documentation of critical information, such as
      discharge medication reconciliation and discharge summary. A handout of an intern
      guide/manual was also provided. The previous year's data served as
      comparison/control data. Comparison data were obtained for both groups from
      hospital's utilisation review department. Results: Twenty-one of 23 expected new
      interns (91%) participated in the intervention. There was a significant decrease
      in non-compliance for clinical documentation in the intervention group compared
      to the control group. The self-reported confidence level in the intervention
      group increased 34%. Conclusions: Such peer-to-peer orientation has the potential
      to effectively improve appropriate documentation and discharge process by new
      residents and may help to reduce the 'July effect'.

PMID- 30181824
TI  - Morbidity pattern and outcome of patients admitted in a coronary care unit: a
      report from a secondary hospital in southern region, Saudi Arabia.
AB  - Background: There is limited information about the clinical profile and outcome
      on patients admitted to a coronary care unit (CCU) in Saudi Arabia is available.
      Objective: The aim of this study was to evaluate reasons for admission, clinical
      characteristics, outcome and predictors of outcome in CCU patients. Materials and
      methods: The data of 392 patients admitted to the CCU of a secondary care centre
      in southern region of Saudi Arabia from 1 January 2017 to 31 December 2017 were
      collected. Data that were extracted from the patients included demographics,
      admission diagnosis and outcome. Results: A total of 392 patients, comprising 305
      (77.81%) males and 87 (22.19%) females, were admitted to the CCU. Their mean age
      was 64.62 +/- 15.7. The most common cause of admission was acute coronary
      syndrome (63.3%), the majority (97.2%) of whom were above 50 years of age (Table
      2). Thirty-one patients died. This figure accounted for 7.7% of all the patients
      admitted to the CCU and 23.4% of the patients that were fully managed in the CCU.
      The majority of the patients that died were those with cardiac arrest (12 out of
      16). Acute coronary syndrome (p = 0.029), cardiac arrest (p = 0.000) and age
      greater than 50 years (p = 0.000) were associated with death in the study
      patients. However, cardiac arrest (p = 0.002) and age greater than 50 years (p =
      0.017) were independent predictors of death in the study patients. Conclusion:
      The reasons for admission to the CCU were acute coronary syndrome, heart failure
      and cardiac arrest. Mortality among CCU patient was comparable to reports
      elsewhere. Cardiac arrest and age greater than 50 years were independent
      predictors of death.

PMID- 30181825
TI  - Association between loop diuretic dose administered in first 24 hours of heart
      failure admissions and length of hospital stay.
AB  - Background: Heart failure remains one of the highest disease burdens in the USA
      and worldwide. Heart failure guidelines recommend starting with a higher or equal
      to home dose of loop diuretics in acute decompensated heart failure admissions.
      To date, no study has been published assessing the effect of first 24 h loop
      diuretic dose on length of hospital stay. Objective: We hypothesize that the
      higher the first 24 h loop diuretic dose to home dose ratio, the shorter the
      length of hospital stay will be. Design/Methods: Retrospective chart review was
      conducted in a community teaching hospital and included patients discharged
      between February, 2015 and April, 2016, with a primary diagnosis of acute
      decompensated heart failure. The primary outcome was the length of hospital stay.
      The study population was divided into three groups based on the hospital to home
      dose ratio. Results: Among the 609 patients included in the data analysis, there
      was no statistically significant difference in length of hospital stay among the
      study groups. Inpatient mortality and incidence of acute kidney injury were
      highest in the group that received a first-24-hours hospital dose that was less
      than their home dose. Percentage of weight loss and 30-day readmission were not
      statistically significantly different among the groups. Conclusion: There was no
      association between the dose ratio and length of hospital stay in each group.
      Additional randomized controlled trials need to be conducted to provide more
      evidence and guidance for dosing loop diuretics in acute decompensated heart
      failure admissions.

PMID- 30181826
TI  - Diabetic nephropathy: newer therapeutic perspectives.
AB  - Diabetic nephropathy (DN is a dreaded consequence of diabetes mellitus,
      accounting for about 40% of end-stage renal disease (ESRD). It is responsible for
      significant morbidity and mortality, both directly by causing ESRD and indirectly
      by increasing cardiovascular risk. Extensive research in this field has thrown
      light on multiple pathways that can be pharmacologically targeted, to control or
      reverse the process of DN. Glomerulocentric approach of DN still continues to
      produce favourable results as evidenced by the recent data on SGLT-2 (sodium
      glucose co-transporter type 2) inhibitors. Beyond the glomerular mechanisms,
      numerous novel pathways have been discovered in the last decade. Some of these
      pathways target inflammatory and oxidative damage, while the others target more
      specific mechanisms such as AGE-RAGE (advanced glycation end products-receptors
      for advanced glycation end products), ASK (apoptotic signal-regulating kinase),
      and endothelin-associated pathways. As a result of the research, a handful of
      clinically relevant drugs have made it to the human trials which have been
      elucidated in the following review, bearing in the mind that there are many more
      to come over the next few years. Ongoing research is expected to inform the
      clinicians regarding the use of the newer drugs in DN. Abbreviations: USFDA:
      Unites States Food and Drug Administration; SGLT-2: Sodium glucose transporter
      type 2; GLP-1: Glucagon-like peptide-1; DDP-4: Dipeptidyl peptidase-4; UACR:
      urinary albumin creatinine ratio; eGFR: Estimated glomerular filtration rate;
      CKD: Chronic kidney disease; DN: Diabetic nephropathy; TGF: Tubuloglomerular
      feedback; RAAS: Renin angiotensin aldosterone system; T1DM: Type 1 diabetes
      mellitus; T2DM: Type 2 diabetes mellitus; RCT: Randomized controlled trial; AGE
      RAGE: Advanced glycation end products-receptors for advanced glycation end
      products; ASK-1: Apoptotic signal-regulating kinase-1; Nrf-2: Nuclear 1 factor
      [erythroid derived-2]-related factor 2; ml/min/1.73m2: Millilitre/minute/1.73
      square meters of body surface area; ~: Approximately.

PMID- 30181827
TI  - Atrial fibrillation and heart failure- results of the CASTLE-AF trial.
AB  - Congestive Heart Failure (HF) and Atrial Fibrillation (AFIB) often coexist.
      Catheter ablation is a well-established option for symptomatic AFIB that is
      resistant to drug therapy in patients with otherwise normal cardiac function.
      This has been seen in various studies where catheter ablation was associated with
      positive outcomes in patients with HF. Recently, the study results from the
      Catheter Ablation versus Standard Conventional Therapy in Patients with Left
      Ventricular Dysfunction and Atrial Fibrillation (CASTLE-AF) trial were published.
      After a median follow-up of more than 3 years, patients getting catheter ablation
      for AFIB had significantly fewer hospital admissions as well as death from
      worsening HF. In addition, 63% of patients in the ablation group were in sinus
      rhythm, as compared with 22% of those in the medical-therapy group (P < 0.001).
      This trial may represent a significant additional therapeutic tool in the
      clinical prevention and management of cardiovascular mortality and morbidity.
      While catheter ablation does not eliminate the AFIB per se, it can limit the
      ventricular rate by eliminating triggers and altering electrophysiological
      connections in the heart in a similar fashion to rate control anti-arrhythmic
      drugs. Longer-duration normal sinus rhythm may improve outcomes by means of a
      number of mechanisms, including greater atrial emptying, all of which translate
      into improved cardiac output. A better understanding is needed as to why a
      decrease in density, but not complete elimination of atrial fibrillation, is
      sufficient for reverse remodelling. It is anticipated that the results of the
      CASTLE-AF trial will soon be implemented in international guidelines.

PMID- 30181828
TI  - Prevalence of chronic obstructive pulmonary disease (COPD) among rheumatoid
      arthritis: results from national inpatient database.
AB  - Rheumatoid arthritis (RA) is being increasingly recognized as an important
      contributor to chronic obstructive pulmonary disease (COPD). Although smoking is
      a major risk factor, other factors may play a role. We used National Inpatient
      Sample (NIS) from 2013 to explore this relationship. We used propensity matching
      with a 1:3 nearest-neighbor-matching algorithm to match 1 RA hospitalization to 3
      age- and-sex-matched comparators. In the age- and-sex-matched population, RA had
      a higher odds of COPD (OR 1.20, 95% CI: 1.17-1.22, p < 0.0001). RA is associated
      with increased COPD prevalence, independent of smoking. COPD might fall within
      the spectrum of RA complications, likely due to autoimmune and inflammatory
      mechanisms.

PMID- 30181829
TI  - Brain metastasis in colorectal cancer presenting as refractory hypertension.
AB  - Background: Brain metastasis (BM) from colorectal cancer (CRC) is rare with the
      incidence ranging from 0.6% to 3.2%. There is also an increased incidence of BM
      with rectal primaries and is consistent with this patient's presentation.
      Overall, there is scarce literature on the symptoms of patients who present with
      CRC BMs. Objectives: We present a case of brain metastasis in colorectal cancer
      presenting with hypertensive urgency and severe headache. Methods and results:
      This case highlights that neurological deficits are not necessary for BMs in
      patients with CRC and summarizes and reviews the associated literature regarding
      BM in CRC. A 57-year-old female with a past medical history of recently diagnosed
      stage IV moderately differentiated distal rectal adenocarcinoma with liver and
      lung metastasis was admitted with the primary complaint of hypertensive urgency,
      severe headache, intractable nausea and vomiting, and diarrhea. Magnetic
      resonance imaging brain showed a left cerebellar lesion measuring 3.6 * 3.2 * 2.9
      cm, ipsilateral transtentorial herniation, and obliteration of the fourth
      ventricle. The patient was started on steroids and transferred for an urgent
      neurosurgical intervention to a tertiary care center. Conclusions: Even though
      BMs are rare in CRC, clinicians should have a high index of suspicion with
      complaints like hypertensive urgency, headache, nausea, vomiting, vertigo, and
      blurring of vision triggering imaging studies to rule out BM. The approach to BM
      has become increasingly individualized as surgical and radiosurgical therapies
      have continued to evolve Abbreviations: CRC: Colorectal cancer; BM: Brain
      metastasis; FOLFOX: Folinic acid, fluorouracil and oxaliplatin; CT: Computed
      tomography; IV: Intravenous; PO: By mouth; BAER: Brain auditory evoked response
      hearing testing; SSEP's: Somatosensory evoked potentials; BMFI: Brain metastasis
      free interval; WBRT: Whole-brain radiation therapy; SRS: Stereotactic
      radiosurgery.

PMID- 30181830
TI  - Hot and malignant - a case of invasive papillary carcinoma in hyperthyroid
      patient with hot nodules.
AB  - Introduction: Malignant thyroid nodules are clinically euthyroid and appear as
      cold nodules on scintigraphy. Malignancy in hyper-functioning thyroid nodule is
      rare. Case report: A 48-year-old male with painless swelling on the right side of
      his neck for the last 4 months complained of feeling hot all the time, sweating
      and unintentionally losing about 20 pounds. On physical examination, there was a
      3-cm mobile, non-tender mass on the right supra-clavicular area biopsy of which
      was consistent with metastatic papillary carcinoma of thyroid. Neck imaging
      showed a cystic mass in the right supra-clavicular fossa region, bilateral neck
      adenopathy and multiple thyroid nodules. Subsequent thyroid radionuclide scans
      showed three hyper-functioning nodules, which were later demonstrated to be a
      follicular variant of papillary microcarcinoma. He was treated with total
      thyroidectomy followed by radioactive iodine thyroid ablation therapy.
      Conclusion: Physicians need to be aware and vigilant for the possibilities of
      malignancy in a hyper-functioning thyroid nodule when evaluating any thyroid
      nodule.

PMID- 30181831
TI  - Delayed spontaneous recanalization of chronic total occlusion of left anterior
      descending artery after attempted but failed revascularization during
      percutaneous coronary intervention.
AB  - Chronic total occlusion (CTO) of coronary artery remains the Achilles heel of the
      interventional cardiologist and is present in a significant proportion of
      referrals for coronary artery bypass graft surgery (CABG); however, with the
      development and standardization of modern CTO recanalization techniques, it has
      been able to achieve excellent success while coping with lesions of increasing
      complexity. Nevertheless, failure to recanalize despite the development of new
      techniques still remains one of the challenges in the field of interventional
      cardiology. Spontaneous recanalization has been described in nonocclusive
      coronary artery dissections in detail; none has addressed the possibility of
      spontaneous recanalization after failed percutaneous coronary intervention (PCI).
      We report a case of spontaneous but delayed recanalization of CTO of left
      anterior descending artery 3 years after attempted but failed revascularization
      during PCI.

PMID- 30181832
TI  - Autoimmune inner ear disease secondary to Hashimoto's thyroiditis: a case report.
AB  - Autoimmune inner ear disease is an important yet incompletely understood cause of
      hearing loss which can present to different medical disciplines. Its diagnostic
      significance is indicated by the fact that it is a reversible medical condition
      if recognized early with an excellent response to immunosuppressive agents.
      Therefore, it should be considered in the differential diagnosis of hearing
      disorders especially in the context of another autoimmune disease such as
      Hashimoto's thyroiditis.

PMID- 30181833
TI  - A diagnosis of late-onset Myasthenia gravis unmasked by topical antibiotics.
AB  - Myasthenia Gravis (MG) is a disorder of the neuromuscular junction (NMJ) that
      manifests as fluctuating fatiguable weakness of the muscles. There are many
      factors that can exacerbate myasthenia symptoms including a variety medications
      and drugs, systemic illness, and pregnancy. A number of medications have been
      implicated in exacerbating MG symptoms, including aminoglycosides. We present a
      case of an elderly female with newly diagnosed MG following the use of tobramycin
      eye drops for 3 days. There have been limited reports in the literature of
      topical medications that exacerbate MG symptoms. Clinicians prescribing
      tobramycin eye drops (or other associated medications) should have a high index
      of suspicion of MG as early discontinuation and therapy will limit long-term
      morbidity and mortality in these patients.

PMID- 30181834
TI  - An unexpected deterrent in diagnosing refractory celiac disease and enteropathy
      associated T-cell lymphoma: a gluten-free diet.
AB  - Enteropathy-associated T-cell lymphoma (EATL) is a rare disease found in the
      small bowel and is seen most commonly in patients with refractory celiac disease
      (RCD). We present a case of an elderly male with celiac disease (CD) diagnosed in
      childhood with months of abdominal pain and diarrhea despite attempting to avoid
      gluten in his diet. After persistent symptoms for months, the patient was
      admitted for an acute abdomen and was found to have small bowel perforation due
      to a jejunal mass that was diagnosed as an EATL. In 2-5% of adult onset CD,
      serious complications such as RCD or malignancy develop. The clinical course for
      EATL is aggressive and generally has a poor prognosis. This case highlights the
      importance of early clinical suspicion for a small bowel malignancy in patients
      with a long-standing history of CD and acute worsening of symptoms. Early workup
      and diagnosis is vital in improving morbidity and mortality in patients with
      EATL.

PMID- 30181835
TI  - A case of acquired hemophilia A in an elderly female.
AB  - Acquired Hemophilia A (AHA) is a bleeding diathesis related to the development of
      factor VIII inhibitor, which can frequently go undetected. It commonly manifests
      as spontaneous mucosal bleeds without any known history of a bleeding disorder,
      but has the potential to cause life threatening bleeding especially in elderly
      patients with underlying comorbidities. Here we describe a case of AHA in a 78
      year old female presenting with spontaneous mucocutaneous bleeding as tongue
      hematoma and recurrent gastrointestinal (GI) bleeding. Underlying etiology
      remained unclear in this case. While she did not require any reversal agents to
      control bleeding, the patient received steroids and rituximab as inhibitor
      eradication therapy.

PMID- 30181836
TI  - Rapid complete atrioventricular heart block reversal due to Lyme carditis.
AB  - A 49-year-old man, who presented with new onset dyspnea on exertion and fatigue
      without clear history of a typical erythema migrans rash, was found to have
      complete atrioventricular (AV) heart block with positive serology for Lyme
      disease. A complete stepwise reversal of the AV block was achieved shortly after
      the initiation of intravenous antibiotic treatment.

PMID- 30181837
TI  - Recurrent autoimmune hemolytic anemia in splenic marginal zone lymphoma.
AB  - Autoimmune hemolytic anemia (AIHA) is a condition associated with an extensive
      differential diagnosis that includes lymphoid malignancies. Although AIHA occurs
      in about 10-25% of patients with chronic lymphocytic leukemia, it is also
      reported to occur in all of the other lymphoid subtypes. In this article, we
      report a case of recurrent AIHA in a 67-year-old woman with two acute episodes of
      hemolysis separated by 3 years of hematologic remission. Both episodes were
      severe enough to require blood transfusion, oral steroids, and rituximab. Bone
      marrow biopsy and immunophenotyping using flow cytometry done during both
      admissions confirmed the presence of splenic marginal zone lymphoma.

PMID- 30181838
TI  - Spinal cord compression due to extramedullary hematopoiesis in a patient with E
      beta-thalassemia managed without radiation or surgery.
AB  - Extramedullary hematopoiesis (EMH) in individuals with thalassemia is often the
      result of undertreated severe anemia. Radiation or surgery is often the chosen
      approach to handle spinal cord compression due to these paraspinal EMH elements.
      Our patient is a 28-year-old male with E-beta-thalassemia who presented with both
      upper thoracic and lower extremity symptoms of spinal cord compression and was
      successfully managed with the combination of transfusion and hydroxyurea. Given
      the variation in symptoms as a result of the sporadic location as well as the
      extent of these EMH elements along the spinal canal, the hematological
      communities will continue to benefit from case reports that offer treatment
      therapy.

PMID- 30181839
TI  - Rare cause of gastric outlet obstruction.

PMID- 30181840
TI  - A Blockchain-Based Notarization Service for Biomedical Knowledge Retrieval.
AB  - Biomedical research and clinical decision depend increasingly on scientific
      evidence realized by a number of authoritative databases, mostly public and
      continually enriched via peer scientific contributions. Given the dynamic nature
      of biomedical evidence data and their usage in the sensitive domain of biomedical
      science, it is important to ensure retrieved data integrity and non-repudiation.
      In this work, we present a blockchain-based notarization service that uses smart
      digital contracts to seal a biomedical database query and the respective results.
      The goal is to ensure that retrieved data cannot be modified after retrieval and
      that the database cannot validly deny that the particular data has been provided
      as a result of a specific query. Biomedical evidence data versioning is also
      supported. The feasibility of the proposed notarization approach is demonstrated
      using a real blockchain infrastructure and is tested on two different biomedical
      evidence databases: a publicly available medical risk factor reference repository
      and on the PubMed database of biomedical literature references and abstracts.

PMID- 30181842
TI  - Clinicopathological parameters influencing inhibitor development in patients with
      hemophilia A receiving on-demand therapy.
AB  - Background: Development of inhibitors to transfused factor VIII in patients with
      hemophilia A continues to be a challenge for professionals involved in hemophilia
      care. The majority of patients in India receive 'on-demand' rather than
      prophylactic therapy. The present study was done to assess the prevalence of
      factor VIII inhibitors in patients with hemophilia A (PWHA) receiving 'on-demand'
      therapy in a North Indian population and to study the clinicopathological
      parameters influencing the development of inhibitors. Methods: The study group
      comprised of 300 PWHA. Detailed clinical parameters, treatment history, bleeding
      profile including family history were recorded. Diagnosis of hemophilia A was
      confirmed by relevant coagulation tests. Inhibitors were screened using mixing
      based studies followed by quantification by Bethesda assay and Nijmegen modified
      Bethesda assay. Samples were collected from five cities in North India where a
      free supply of factor VIII was available and effectively used in three of these
      cities. Results: In the 300 PWHA, disease phenotype was severe in 219 (73%),
      moderate in 62 (20.67%) and mild in 19 (6.34%), based on the factor VIII
      bioassay. Inhibitor prevalence was 9.6% (n = 29) and seen only in the severe
      phenotype. Inhibitor titers ranged from 0.8 to 108.8 BU/ml. A total of 12 PWHA
      had low and 17 had high titers. Correlation of various clinicopathological
      parameters in inhibitor-positive versus negative PWHA showed significant
      correlation with age at onset of disease, severity of disease, age at first
      exposure to treatment, annual factor intake (IU/kg/year), intense treatment
      episodes and bleeding manifestations like central nervous system bleed and
      hematuria. The total study sample had blood group B in 33.34% PWHA, followed by O
      (27.34%), A (24.34%) and AB (15%), however, in inhibitor-positive samples,
      significant inhibitor formation was associated with the ABO subtype A (19/29,
      65.51%). Conclusions: Factor VIII inhibitor prevalence in PWHA receiving 'on
      demand' therapy was 9.6%. Clinicopathological correlates of inhibitor development
      in such PWHA have been analyzed in this novel study.

PMID- 30181841
TI  - Advances in Human Placental Biomechanics.
AB  - Pregnancy complications are a major clinical concern due to the related maternal
      and fetal morbidity. Many are caused through defective placentation, but research
      into placental function is difficult, principally because of the ethical
      limitations associated with the in-vivo organ and the difficulty of extrapolating
      animal models. Perfused by two separate circulations, the maternal and fetal
      bloodstreams, the placenta has a unique structure and performs multiple complex
      functions. Three-dimensional imaging and computational modelling are becoming
      popular tools to investigate the morphology and physiology of this organ. These
      techniques bear the potential for better understanding the aetiology and
      development of placental pathologies, however, their full potential is yet to be
      exploited. This review aims to summarize the recent insights into placental
      structure and function by employing these novel techniques.

PMID- 30181843
TI  - Recent advances in musculoskeletal physiotherapy for haemophilia.
AB  - Physiotherapy is directed towards the movement needs and potential of
      individuals, providing treatment and rehabilitation to develop, maintain and
      restore maximum movement and functional ability throughout the lifespan. Recent
      systematic reviews and randomized controlled trials have extended evidence for
      the clinical efficacy of physiotherapy interventions and rehabilitation for
      people with haemophilia. This narrative review synthesizes recent evidence to
      discuss; differentiating musculoskeletal bleeding and haemophilic arthropathy,
      efficacy of physiotherapy and rehabilitation for acute musculoskeletal bleeding
      and arthropathy, as well as monitoring musculoskeletal health. Whilst robust
      evidence is emerging, there is a need for more well designed randomized clinical
      studies with larger numbers and homogeneity of participants and collaboration of
      all researchers and clinicians to identify a core set of outcome measures that
      can be used to monitor musculoskeletal health.

PMID- 30181844
TI  - The role of patient and healthcare professionals in the era of new hemophilia
      treatments in developed and developing countries.
AB  - Medical decisions in hemophilia care are primarily related to the type of factor
      replacement and treatment regimen. With the growing number of treatment options
      for patients with hemophilia, decision making is more complex and requires
      careful consideration of benefits, risks, and patient goals. Shared decision
      making and decision-aid tools facilitate patient and healthcare provider
      communication. In this review, the overall role of shared decision making in
      medicine is outlined, with special emphasis on models for practical
      implementation. Examples of shared decision making in hemophilia are outlined,
      and application to new therapeutics is discussed through a case-based approach.

PMID- 30181845
TI  - Dupilumab in atopic dermatitis: rationale, latest evidence and place in therapy.
AB  - Atopic dermatitis (AD) is one of the most common chronic inflammatory skin
      diseases. The prevalence of AD is increasing and is currently estimated at 10-20%
      in adults worldwide. In the majority of patients, AD can be adequately controlled
      with topical treatment or ultraviolet light therapy, but there is a high unmet
      need for effective and safe therapeutics in patients with more severe or
      difficult to treat AD. During the past decade, new advances in the understanding
      of the underlying immune pathogenesis of AD have led to the development of new,
      more targeted therapies. Dupilumab, a fully human monoclonal antibody targeting
      the interleukin (IL)-4 receptor alpha, thereby blocking the IL-4 and IL-13
      pathway, is one of the first biologics that has been developed for AD. Dupilumab
      has shown promising results in phase III trials and has recently been approved by
      the US Food and Drug Administration and the European Commission for the treatment
      of moderate to severe AD. With the approval of dupilumab, we are entering a new
      era of biological therapeutics in AD management. The place of dupilumab should be
      established in the current treatment standards. Based on current treatment
      guidelines and experts' opinions in the management of AD, we have built a
      proposal for a treatment algorithm for systemic treatment of AD in European
      countries.

PMID- 30181846
TI  - Tolerability and clinical efficacy of inhaled treprostinil in patients with group
      1 pulmonary arterial hypertension.
AB  - Background: Treprostinil is a prostacyclin analogue that directly vasodilates
      pulmonary and systemic arterial vascular beds. The United States Food and Drug
      Administration approved inhaled treprostinil in July 2009 for the treatment of
      group 1 pulmonary arterial hypertension. Inhaled treprostinil avoids issues with
      continuous infusion prostanoids. This study describes a single institutional
      experience with inhaled treprostinil. Methods: This was a retrospective review of
      group 1 pulmonary arterial hypertension patients receiving inhaled treprostinil
      from July 2009 through September 2015. Patient demographics, vital signs,
      prognostic indicators, pulmonary arterial hypertension assessments, treprostinil
      dosing, pulmonary arterial hypertension medications, and physician assessment
      were collected. Prognostic indicators and the physician assessment were used to
      assess treatment response. A modified Registry to Evaluate Early and Long-term
      Pulmonary Arterial Hypertension Disease Management (REVEAL) risk score was
      calculated prior to and after initiation of inhaled treprostinil. Results: The
      mean time on inhaled treprostinil for the 16 patients was 21 +/- 17 months. A
      total of 31% discontinued treatment. The New York Heart Association Functional
      Class, right ventricular size, and right ventricular function improved after
      inhaled treprostinil. Directional improvement in B-type natriuretic peptide, 6
      minute walk distance, right arterial pressure and mean pulmonary artery pressure
      were also observed. The mean modified REVEAL risk score (RRS) was 7 +/- 3 at
      baseline. The RRS decreased in 7 of the 11 patients that improved and remained
      stable in 2 patients. Conclusion: The majority of patients in this consecutive
      series receiving inhaled treprostinil tolerated treatment. Most patients remained
      on therapy for over 12 months. Clinical assessments of disease severity all
      changed directionally toward improvement and the overall risk assessment was
      improved or stable in 56% by the RRS.

PMID- 30181847
TI  - Assessing the incidence of acidosis in patients receiving metformin with and
      without risk factors for lactic acidosis.
AB  - Background: Despite strong recommendations to use metformin as first-line therapy
      for type 2 diabetes (T2DM), its use has been suboptimal, likely due to concerns
      of lactic acidosis. This study compared the association of acidosis in patients
      with T2DM prescribed metformin with those prescribed other antihyperglycemic
      medications or no medications. Methods: This was a retrospective cohort study of
      patients with newly diagnosed T2DM utilizing an administrative database, which
      includes medical and prescription claims. Eligible patients had a diagnosis of
      T2DM, had continuous health plan enrollment 3 months prior to study enrollment
      and during the study period, and were at least 18 years of age. Mutually
      exclusive exposure groups were metformin only, other antihyperglycemic
      medications, and no medication. Acidosis cases were stratified by exposure group
      and risk factors for lactic acidosis (chronic obstructive pulmonary disease,
      hepatic dysfunction, alcohol abuse, heart failure, renal insufficiency, age of 80
      years or older, and a history of acidosis). Degree of renal insufficiency was not
      available. Associations between exposure and acidosis were estimated, and risk
      factors evaluated. Results: A total of 132,780 patients met inclusion criteria:
      24,936 (20%) metformin only group, 15,059 (11%) other antihyperglycemic
      medication group, and 92,785 (70%) no medication group. Acidosis was observed in
      1.45 per 10,000 patient months (0.78 metformin, 1.59 other antihyperglycemic
      medication, 1.51 no medication). The unadjusted relative risk of acidosis was 0.5
      for patients prescribed metformin only compared with the other exposure groups
      (95% confidence interval = 0.2-1.2). There was no significant difference in risk
      of acidosis between exposure groups, irrespective of risk factors for lactic
      acidosis. Conclusions: Risk of acidosis was similar with metformin only compared
      with those prescribed other antihyperglycemic medications or no medication. These
      results support expanded use of metformin for T2DM. Additional studies are needed
      to understand the impact of risk factor severity on risk of lactic acidosis.

PMID- 30181848
TI  - The clinical significance of hyperglycemia in nondiabetic critically ill multiple
      trauma patients.
AB  - Background: Information is inconsistent regarding the clinical role of acute
      elevations of blood glucose level secondary to hospital-acquired infections in
      nondiabetic critically ill patients during an intensive care unit stay. In this
      study we investigated the clinical significance of hyperglycemia related to new
      episodes of ventilator-associated pneumonia in nondiabetic critically ill
      multiple trauma intensive care unit patients. Materials and Methods: We analyzed
      the clinical data of 202 critically ill multiple trauma patients with no history
      of previous diabetes who developed a new ventilator-associated pneumonia episode
      during their intensive care unit stay. We used a time-from-event analysis method
      to assess whether acute changes in blood glucose levels that occurred prior to
      the onset of ventilator-associated pneumonia episodes had a different prognostic
      significance from those that occurred during such episodes. Glucose levels and
      other laboratory data were recorded for up to 5 days before ventilator-associated
      pneumonia events and for 5 days following these events. Results: Patients who
      required insulin therapy for persistent hyperglycemia related to a new ventilator
      associated pneumonia event had a longer period of intensive care unit stay and a
      higher intensive care unit mortality rate than patients who did not require
      insulin for blood glucose control (p < 0.008 and <0.001 respectively). In
      addition, older age, administration of parenteral nutrition, and elevated mean
      blood glucose level parameters on the day following the day of diagnosis of a new
      ventilator-associated pneumonia episode were found to be independent risk factors
      for intensive care unit mortality. Conclusion: Our study suggests that persistent
      hyperglycemia in nondiabetic critically ill patients, even treated by early
      insulin therapy, is an adverse prognostic factor of considerable clinical
      significance.

PMID- 30181849
TI  - Diabetes education and medication adjustment in Ramadan (DEAR) program prepares
      for self-management during fasting with tele-health support from pre-Ramadan to
      post-Ramadan.
AB  - Background: We evaluated the outcome for fasting Muslims with diabetes prepared
      with pre-Ramadan optimization through education and medication adjustment, tele
      support and intervention up to post-Ramadan. Methods: Muslims with diabetes
      planning to fast were recruited into a focused diabetes program for Ramadan
      fasting.It consisted of (a) a pre-Ramadan assessment and test fasting to optimize
      glycemic control, (b) education on diabetes management during fasting, (c) tele
      monitoring from pre-Ramadan and (d) a post-Ramadan review. Their metabolic
      profiles and diaries for meals, activities and glucose monitoring were evaluated.
      Results: Twenty-nine participants were enrolled, with mean age 58.4 +/- 9.2
      years, 75.9% female, 79.3% Malays and 93.1% type 2 diabetes. A total of 92%
      needed medication adjustment and 93% fasted for at least 14 days. Glycated
      hemoglobin (HbA1c) and weight decreased from 8.8 +/- 1.8% (72.7 mmol/mol) pre
      Ramadan to 8.5 +/- 1.7% (69.4 mmol/mol) post-Ramadan and 76.6 +/- 20.3 kg pre
      Ramadan to 75.9 +/- 21.3 kg post-Ramadan, respectively. There were decreased
      complications of hypoglycemia from 13.8% to 10.3% and several-fold improvement in
      hyperglycemia from 31.0% to 3.5% during Ramadan fasting when compared with pre
      Ramadan. Conclusions: Muslims with diabetes were able to self-manage when fasting
      using tele-monitoring support and intervention, with decreased complications
      during Ramadan compared with pre-Ramadan.

PMID- 30181850
TI  - Effectiveness and safety of insulin glargine versus detemir analysis in patients
      with type 1 diabetes: systematic review and meta-analysis.
AB  - Background: Diabetes mellitus type 1 (DM1) is an autoimmune disease characterized
      by metabolic destruction of pancreatic cells responsible for insulin production,
      with treatment based on replacing insulin. Long-acting insulin analogs are
      indicated for patients with DM1 who exhibit important oscillations of their daily
      glycemia, despite its higher cost. Our study objective was to evaluate the
      effectiveness and safety of two long-acting insulins, insulin glargine and
      detemir, in treating patients with DM1. Methods: We undertook a systematic review
      with meta-analysis of observational studies (cohort and registry) available in
      the databases and the gray literature, and a complementary search in the Diabetes
      Care journal. Outcomes assessed were: glycated hemoglobin concentration; fasting
      plasma or capillary glucose; occurrence of episodes of severe hypoglycemia and
      occurrence of nocturnal hypoglycemia. The assessment of methodological quality
      was performed using the Newcastle score. The meta-analyses were performed on
      software Review Manager(r) 5.2. Results: Out of 705 publications, 8 cohort
      studies were included. The quality of these studies was classified as high. In
      the meta-analysis, results regarding episodes of severe hypoglycemia (p = 0.02)
      and fasting glucose (p = 0.01) were in favor of detemir. The glycated hemoglobin
      (p = 0.49; I2 = 89) showed high heterogeneity and no statistically significant
      difference between the two. The meta-analysis of total insulin dose favored
      glargine (p = 0.006; I2 = 75). The rates of nocturnal hypoglycemia (NH) were
      evaluated only for one study and showed a significant reduction of NH after
      therapy with detemir, (p < 0.0001). Conclusion: Although some outcomes were
      favorable to detemir insulin analog, it has not been possible to identify
      important differences of effectiveness and safety between the two analogs. These
      results can help in the current debate on the inclusion of long-acting analogs on
      the list of reimbursed medicines in Brazil, especially with the recent
      introduction of an insulin glargine biosimilar at a considerably lower price.

PMID- 30181851
TI  - 5-alpha-dihydrotestosterone elevations associated with phentermine use.
AB  - Background: A case of 5-alpha-dihydrotestosterone (DHT) elevation associated with
      phentermine initiation is reported, and possible mechanisms are discussed. There
      are no published reports of this association in the literature. Methods: Clinical
      and laboratory information is described. Results: A 72-year-old male with
      metastatic prostate cancer taking dutasteride to lower his DHT levels initiated
      phentermine 15 mg daily for weight loss. His DHT level drawn within 1 week prior
      to starting phentermine was 9.9 pg/ml. When reporting for follow up 2 weeks
      later, his DHT level had increased to 114 pg/ml. The DHT level was checked again
      2 weeks after that visit, and had increased to 174 pg/ml. At that time,
      phentermine was discontinued, and 1 week later, the DHT level had decreased to
      20.1 pg/ml. Over the next 4 months, the patient's DHT levels were maintained at
      less than 20 pg/ml. Phentermine 15 mg daily was then reinitiated while his DHT
      level was 7.5 pg/ml. Two weeks after resuming phentermine, his DHT level had
      again increased to 196 pg/ml. The patient's phentermine was then discontinued,
      and around 1 week later, his DHT level had fallen to 5.1 pg/ml. Conclusion: A 72
      year-old male with metastatic prostate cancer experienced profound increases in
      DHT upon initiation of phentermine despite continuation of his baseline
      dutasteride therapy. The etiology of these increases is still unclear.

PMID- 30181853
TI  - Use of dapagliflozin as an add-on to insulin therapy in patients with
      suboptimally controlled type 2 diabetes.

PMID- 30181852
TI  - Drug interactions of meglitinide antidiabetics involving CYP enzymes and OATP1B1
      transporter.
AB  - Meglitinides such as repaglinide and nateglinide are useful to treat type 2
      diabetes patients who follow a flexible lifestyle. They are short-acting insulin
      secretagogues and are associated with less risk of hypoglycemia, weight gain and
      chronic hyperinsulinemia compared with sulfonylureas. Meglitinides are the
      substrates of cytochrome P450 (CYP) enzymes and organic anion transporting
      polypeptide 1B1 (OATP1B1 transporter) and the coadministration of the drugs
      affecting them will result in pharmacokinetic drug interactions. This article
      focuses on the drug interactions of meglitinides involving CYP enzymes and
      OATP1B1 transporter. To prevent the risk of hypoglycemic episodes, prescribers
      and pharmacists must be aware of the adverse drug interactions of meglitinides.

PMID- 30181854
TI  - Traditional clinical criteria outperform high-sensitivity C-reactive protein for
      the screening of hepatic nuclear factor 1 alpha maturity-onset diabetes of the
      young among young Asians with diabetes.
AB  - Background: Young adults with diabetes in Asia represent a heterogeneous group.
      Using traditional clinical criteria to preselect individuals for testing for
      maturity-onset diabetes of the young (MODY) may exclude a large proportion from
      testing. High-sensitivity C-reactive protein (hs-CRP) has shown promise as a
      biomarker to differentiate hepatic nuclear factor 1 alpha (HNF1A)-MODY from type
      2 diabetes. We aimed to compare the use of hs-CRP as a biomarker versus
      traditional criteria, to guide testing for HNF1A-MODY among a cohort of young
      adults with diabetes in Singapore. Methods: A total of 252 adults (age of onset
      ?45 years) and 20 children with diabetes were recruited. Using traditional
      criteria (family history of diabetes and onset of diabetes ?25 years) and an hs
      CRP cut off of ?0.5 mg/l, 125 and 37 adults, respectively, were identified for
      HNF1A gene testing. All children underwent HNF1A gene testing. Results: Five
      adults (5/143, 3.5%) with HNF1A-MODY were identified. There were no HNF1A gene
      mutations among the children. Traditional criteria correctly identified all five
      HNF1A-MODY individuals (5/125, 4%), while applying an hs-CRP level of ?0.5 mg/l
      selected just 1 of these 5 for HNF1A gene testing (1/37, 2.7%). None of those
      with a positive GAD antibody or undetectable C-peptide level had HNF1A-MODY.
      Conclusion: The use of hs-CRP to guide screening for HNF1A-MODY among Asian young
      adults with diabetes did not improve the diagnostic yield. Applying a combination
      of age of onset of diabetes under 25 years and a family history of diabetes alone
      could guide targeted HNF1A-MODY screening in Asians, with an expected yield of 4%
      diagnosed with HNF1A-MODY among those screened.

PMID- 30181855
TI  - Cross-sectional correlates of myeloperoxidase and alpha-1-acid glycoprotein with
      adiposity, atherogenic and hematological indices in metabolic syndrome patients
      with or without diabetes.
AB  - Background: Type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) are
      associated with obesity, which triggers the release of inflammatory substances.
      Myeloperoxidase (MPO), a peroxidase enzyme, and alpha-1-acid glycoprotein (AGP),
      an acute-phase protein, are known to be released in patients with inflammatory
      conditions and cardiovascular disease (CVD). Methods: In this study, we
      investigated the correlation between MPO and AGP levels in pre/diabetic and MetS
      patients by conducting a cross-sectional study at The University of Jordan
      Hospital (UoJH) at the diabetes and endocrinology outpatient clinics. A total of
      237 patients were recruited and assessed for eligibility. Of these, 149 patients
      were excluded, and 88 patients were assigned as: 29 patients in a healthy lean
      normoglycemic control group; 29 patients in a nondiabetic MetS group; and 30
      patients in a prediabetic/newly diagnosed T2DM MetS group. Results: MPO levels
      were only significantly higher in the nondiabetic MetS group compared with the
      control group (p = 0.026). AGP levels were significantly higher in both
      nondiabetic MetS and MetS-prediabetic/T2DM groups versus control (p = 0.007 and p
      = 0.015, respectively). Both biomarkers lacked inter-MetS-group discrepancy.
      Conclusions: Our results demonstrate an association between MPO and AGP with
      obesity and hyperglycemia, alongside their correlation with several adiposity,
      hematology and atherogenicity indices. Our findings reinforce the use of MPO and
      AGP as potentially putative and surrogate predictive/prognostic tools for MetS
      and its related disorders.

PMID- 30181856
TI  - Reference intervals of thyroid hormones in a previously iodine-deficient area in
      Darfur, Sudan.
AB  - Background: Thyroid-stimulating hormone (TSH), thyroxin (T4) and T3 levels are
      varied in the different settings with disorders of thyroid homeostasis. It is
      recommended that every setting has to establish its own reference intervals (RIs)
      for these hormones. Methods: A multi-stage stratified sampling method was used to
      select a representative sample of a Sudanese adult (>20 years of age) in Nyala in
      western Sudan in the Darfur region during the period between January and June
      2016 to establish RIs of thyroid-related hormones (TSH, T4 and T3).In this study,
      1753 serum samples (male and female) with different age groups were investigated.
      A radioimmunoassay gamma counter was used to measure the level of these hormones.
      Results: The median (95% intervals) of serum TSH, T4 and T3 levels was 1.2 (0.50
      3.0) mIU/l, 111.0 (72.0-161.0) nmol/l and 1.5 (0.8-2.8) nmol/l respectively.While
      the level of TSH was significantly higher in the age group between 31 and 40
      years, both T4 and T3 levels have shown a progressive increase with age. There
      was no significant difference in the TSH, T4 and T3 level when the RIs were
      compared between males and females. Conclusion: The RIs for TSH, T4 and T3 in
      this setting were different from the levels provided by the manufacturers. The
      RIs were different in the different age groups.

PMID- 30181857
TI  - Considerations for total thyroidectomy in an adolescent with PTEN mutation.
AB  - Individuals with PTEN Hamartoma Tumor Syndrome (PHTS) are at greatly increased
      risk for developing well-differentiated thyroid cancer. Specific circumstances in
      which total thyroidectomies should be considered have not been defined. A 14-year
      old macrocephalic female with history of developmental delay and lipoma over her
      left flank presented with neck swelling and was found have multinodular goiter
      and auto-immune thyroiditis. Asymptomatic tracheal narrowing was also detected on
      her initial diagnostic imaging. Later on, she developed positional dyspnea during
      sleep. Genetic testing revealed a heterozygous pathogenic variant in the PTEN
      gene (c.463T>A). A total thyroidectomy was performed. In addition to addressing
      the symptomology in our case, a total thyroidectomy also fortuitously eliminated
      the thyroid cancer risk. This case spurred us on further to identify specific
      clinical scenarios where total thyroidectomy may be considered as a true
      prophylactic measure to manage thyroid cancer risk in PHTS patients.

PMID- 30181858
TI  - Effect of a voice recognition system on pediatric outpatient medication errors at
      a tertiary healthcare facility in Kenya.
AB  - Background: Medication-related errors account for one out of every 131 outpatient
      deaths, and one out of 854 inpatient deaths. The risk is threefold greater in the
      pediatric population. In sub-Saharan Africa, research on medication-related
      errors has been obscured by other health priorities and poor recognition of harm
      attributable to such errors.Our primary objective was to assess the effect of
      introduction of a voice recognition system (VRS) on the prevalence of medication
      errors. The secondary objective was to describe characteristics of observed
      medication errors and determine acceptability of VRS by clinical service
      providers. Methods: This was a before-after intervention study carried out in a
      Pediatric Accident and Emergency Department of a private not-for-profit tertiary
      referral hospital in Kenya. Results: A total of 1196 handwritten prescription
      records were examined in the pre-VRS phase and 501 in the VRS phase. In the pre
      VRS phase, 74.3% of the prescriptions (889 of 1196) had identifiable errors
      compared with 65.7% in the VRS phase (329 of 501).More than half (58%) of
      participating clinical service providers expressed preference for VRS
      prescriptions compared with handwritten prescriptions. Conclusions: VRS reduces
      medication prescription errors with the greatest effect noted in reduction of
      incorrect medication dosages. More studies are needed to explore whether more
      training, user experience and software enhancement would minimize medication
      errors further. VRS technology is acceptable to physicians and pharmacists at a
      tertiary care hospital in Kenya.

PMID- 30181859
TI  - Identifying and assessing potential harm of medication errors and potentially
      unsafe medication practices in paediatric hospital settings: a field study.
AB  - Background: Hospitalized children are prone to experience harm from medication
      errors (MEs). Strategies to prevent MEs can be developed from identified
      malfunctioning practices and conditions in the medication use process. In this
      study, we aimed to identify MEs and potentially unsafe medication practices
      (PUMPs) in hospitalized children, and to assess the potential harm of these,
      using raters of different professions. Methods: A 1-week observation using an
      undisguised technique was conducted on four paediatric hospital wards. One
      observer followed ward staff during medication prescribing, preparation and
      administration. MEs and PUMPs were documented using field notes. Three raters
      including a physician, a nurse and a clinical pharmacist assessed the potential
      harm of each ME and PUMP using a six-point Likert scale. Agreement was analysed
      using Fleiss' Kappa. Results: A total of 16 MEs and 809 PUMPs were identified
      involving a preparation and administration error rate of 8%. No actual harm to
      patients was observed during the study. Raters assessed the potential harm of 318
      unique MEs and PUMPs. Only slight agreement was found (Kappa = 0.26-0.33). A 4
      hour delay in the administration of intravenous cefuroxime received the highest
      harm score. Observations involving no information during prescribing and
      variations in medication preparation were considered potentially fatal for
      medications such as digoxin, morphine, enoxaparin and insulin. Conclusions: MEs
      and potentially unsafe practices and conditions may affect medication safety of
      hospitalized children. However, observed MEs did not result in any harm. The
      agreement among raters assessing the potential harm of observations was low.
      Alternative methods to determine the clinical relevance of errors are needed.

PMID- 30181860
TI  - Shed-MEDS: pilot of a patient-centered deprescribing framework reduces
      medications in hospitalized older adults being transferred to inpatient postacute
      care.
AB  - Background: Polypharmacy is common in hospitalized older adults. Deprescribing
      interventions are not well described in the acute-care setting. The objective of
      this study was to describe a hospital-based, patient-centered deprescribing
      protocol (Shed-MEDS) and report pilot results. Methods: This was a pilot study
      set in one academic medical center in the United States. Participants consisted
      of a convenience sample of 40 Medicare-eligible, hospitalized patients with at
      least five prescribed medications. A deprescribing protocol (Shed-MEDS) was
      implemented among 20 intervention and 20 usual care control patients during their
      hospital stay. The primary outcome was the total number of medications
      deprescribed from hospital enrollment. Deprescribed was defined as medication
      termination or dose reduction. Enrollment medications reflected all prehospital
      medications and active in-hospital medications. Baseline characteristics and
      outcomes were compared between the intervention and usual care groups using
      simple logistic or linear regression for categorical and continuous measures,
      respectively. Results: There was no significant difference between groups in mean
      age, sex or Charlson comorbidity index. The intervention and control groups had a
      comparable number of medications at enrollment, 25.2 (+/-6.3) and 23.4 (+/-3.8),
      respectively. The number of prehospital medications in each group was 13.3 (+/
      4.6) and 15.3 (+/-4.6), respectively. The Shed-MEDS protocol compared with usual
      care significantly increased the mean number of deprescribed medications at
      hospital discharge and reduced the total medication burden by 11.6 versus 9.1 (p
      = 0.032) medications. The deprescribing intervention was associated with a
      difference of 4.6 [95% confidence interval (CI) 2.5-6.7, p < 0.001] in
      deprescribed medications and a 0.5 point reduction (95% CI -0.01 to 1.1) in the
      drug burden index. Conclusions: A hospital-based, patient-centered deprescribing
      intervention is feasible and may reduce the medication burden in older adults.

PMID- 30181861
TI  - Medication use and potentially inappropriate prescribing in older adults with
      intellectual disabilities: a neglected area of research.
AB  - It is known that for all adults, prevalence of potentially inappropriate
      prescribing (PIP) and polypharmacy increases with advancing age and morbidity.
      This has been associated with adverse drug reactions and poor outcomes. As a
      result, screening tools have been developed to identify PIP and to improve
      prescribing and health outcomes. A growing body of evidence supports the fact
      that there are even greater concerns among older adults with intellectual
      disability (ID) who are living longer than before but still have premature
      mortality and poorer health outcomes compared with the general population. They
      have different patterns of multimorbidity, with higher rates of epilepsy and
      mental health conditions. Polypharmacy is prevalent and some prescribing
      practices may be inappropriate. High exposure to anticholinergic and sedative
      medicines has additional adverse effects on quality of life. There may also be
      underutilization of clinically needed therapies. There has been substantial
      controversy internationally relating to extensive use of psychotropic medicines,
      particularly off-label use for challenging behaviours. Despite the mounting
      evidence and concerns about the impact of PIP on quality of life, health and
      safety for people with ID, appropriate methods to measure PIP are lacking, which
      represents an important gap in the research literature. Differences in morbidity
      and medicines use patterns in this population mean instruments used to identify
      inappropriate medicines in the older population are not suitable. In this
      perspective article we outline the specific health and medicinal needs for people
      with ID, the prevalence of polypharmacy and presentation of chronic health
      conditions in older adults with ID. We provide an overview of the psychotropic
      medicine classes most frequently used in people with ID which carry substantial
      risk. We highlight studies to date that have attempted to assess PIP and present
      research priorities to improve prescribing, health outcomes and quality of life
      for people with ID.

PMID- 30181862
TI  - Using EMR-enabled computerized decision support systems to reduce prescribing of
      potentially inappropriate medications: a narrative review.
AB  - Prescribing of potentially inappropriate medications (PIMs) that pose more risk
      than benefit in older patients is a common occurrence across all healthcare
      settings. Reducing such prescribing has been challenging despite multiple
      interventions, including educational campaigns, audits and feedback, geriatrician
      assessment and formulary restrictions. With the increasing uptake of electronic
      medical records (EMRs) across hospitals, clinics and residential aged care
      facilities (RACFs), integrated with computerized physician order entry (CPOE) and
      e-prescribing, opportunities exist for incorporating clinical decision support
      systems (CDSS) into EMR at the point of care. This narrative review assessed the
      process and outcomes of using EMR-enabled CDSS to reduce the prescribing of PIMs.
      We searched PubMed for relevant articles published up to January 2018 and focused
      on those that described EMR-enabled CDSS that assisted prescribers to make
      changes at the time of ordering PIMs in adults. Computerized systems offering
      only medication reconciliation, dose checks, monitoring for medication errors, or
      basic formulary information were not included. In addition to outcome measures of
      medication-related processes and adverse drug events, qualitative data relating
      to factors that influence effectiveness of EMR-enabled CDSS were also gathered
      from selected studies. We analysed 20 studies comprising 10 randomized trials and
      10 observational studies performed in hospitals (n = 8), ambulatory care clinics
      (n = 9) and RACFs (n = 3). Studies varied in patient populations (although most
      involved older patients), type of CDSS, method of linkage with EMR, study designs
      and outcome measures. However, assuming little publication bias, the totality of
      evidence favoured EMR-enabled CDSS as being effective in reducing the prescribing
      of PIMs in hospitals, although results were more mixed for ambulatory care
      settings and RACFs. While absolute effects in most positive studies were modest,
      they suggest EMR-enabled CDSS are feasible and acceptable to clinicians, and if
      certain design features are adhered to, there is potential for even greater
      impact.

PMID- 30181863
TI  - Poorly differentiated signet ring cell carcinoma of pancreas masquerading as
      chronic pancreatitis.
AB  - Pancreatic cancer is typically arises in the context of inflammation, and a
      surrounding area of pancreatitis is often present within the tumor
      microenvironment. Signet ring cell carcinoma (SRCC) is a rare variant of
      pancreatic adenocarcinoma. Pathologically, it presents either as single cells or
      loose clusters masquerading in the background of pancreatitis. Sampling of these
      inflammatory cells during biopsy can result in the incorrect diagnosis of
      pancreatitis. We report a case of SRCC of the pancreas which the diagnosis of
      cancer was delayed because multiple biopsies revealed only inflammatory changes
      with no obvious evidence of malignancy. This case highlights the fact that
      negative results with endoscopic ultrasound fine needle aspiration in SRCC can be
      misleading. A cancer diagnosis should still be considered despite findings of
      inflammatory pancreatitis if the clinical presentation is concerning for cancer
      (mass on CT scan).

PMID- 30181864
TI  - Adenocarcinoma of jejunum.
AB  - Although gastrointestinal malignancy is still the major concern of health
      problems in Worldwide and Thailand, but small intestinal malignancy is extremely
      rare. The location of small intestinal malignancy is duodenum (73.6%), jejunum
      (13.2%) and ileum (13.2%). The diagnosing of small intestinal malignancy usually
      delays due to inaccessible of esophagogastroduodenoscopy especially jejunum and
      ileum causing poor prognostic outcomes. We reported our case of jejunal
      adenocarcinoma.

PMID- 30181865
TI  - Survival from a 75% TBSA thermal injury complicated by bowel ischemia presenting
      with pneumatosis intestinalis.
AB  - Thermal injury is associated with an increased risk of abdominal complications
      such as ischemia, infarction and pneumatosis intestinalis (PI). PI is
      characterized by gas in the intestinal wall and, when diagnosed it can signify
      the presence of a life-threatening condition. We present a case of a patient who
      survived 75% total body surface area burns complicated by ischemic bowel that
      initially presented as extensive PI. This patient was emergently taken to the
      operating room and underwent a subtotal colectomy and small bowel resection for
      ischemic bowel. Prompt diagnosis and successful management of the underlying
      condition ultimately contributed to the patient's survival. The presence of
      peritonitis or abdominal distension, portomesenteric venous gas and lactic
      acidosis should prompt immediate surgical intervention in the post-burn period.

PMID- 30181866
TI  - Haloperidol decanoate long-acting injection (HDLAI): Results of a 1-year mirror
      image study.
AB  - Background: We sought to determine clinical outcomes of the prescribing of
      haloperidol decanoate long-acting injection (HDLAI) at 1 year. Method: A 1-year
      mirror-image study of 84 inpatients initiated on HDLAI. Admissions and bed days
      in the year preceding HDLAI were compared with the year after initiation.
      Predictors for discontinuation were evaluated. Results: At 1 year, 33% of
      patients remained on treatment. Patients starting HDLAI because of nonadherence
      were more likely to stop treatment [relative risk (RR) 1.72; 95% confidence
      interval (CI) 1.01, 2.91; p = 0.044] whilst patients with a longer duration of
      illness were more likely to remain on treatment (RR 0.88; 95% CI 0.78, 1.00; p =
      0.050). In the bed days cohort overall, (n = 65), there was a significant
      reduction in mean hospital admissions (1.4/patient/year to 0.6/patient/year; p =
      0.0001) but not bed days (55.6/patient to 45.0/patient; p = 0.07) in the year
      following HDLAI initiation compared with the year before. Continuers had a
      significant reduction in mean bed days (53.1 to 4.0; p = 0.0002) and hospital
      admissions (1.5 to 0.2; p = 0.0001). Discontinuers demonstrated a significant
      reduction in hospital admissions (1.5 to 0.8; p = 0.0001) but not bed days (56.7
      to 64.5; p = 0.83). Conclusion: HDLAI was associated with a high treatment
      discontinuation rate. Hospital admissions fell in the year after HDLAI but there
      was no change in bed days. Our study suggests that patients with a longer
      duration of illness and patients initiated on HDLAI for reasons other than poor
      adherence may benefit from HDLAI initiation.

PMID- 30181868
TI  - Feasibility of the consultation-based reassurance questionnaire in Danish
      chiropractic practice.
AB  - Background: Reassuring information is recommended in clinical guidelines for the
      treatment of low back pain (LBP), but has not been clearly defined. The
      Consultation-based Reassurance Questionnaire (CRQ) was developed as a tool for
      measuring to what extent reassurance is present in back pain consultations and
      may provide important information about the clinical encounter. Until now the CRQ
      has only been tested in general practice patients in the UK although many
      patients with LBP are seen outside of this setting. The objectives of this study
      were to translate the CRQ into Danish, test its feasibility in chiropractic
      practice, and determine if CRQ scores were associated with satisfaction with care
      and perceived pain control. Methods: On the day of the first visit for a LBP
      episode, patients received an electronic survey including the CRQ. Distributions
      and completeness of responses on the four subscales of the CRQ (data-gathering,
      relationship-building, generic reassurance, cognitive reassurance) were assessed,
      and internal consistency for each subscale calculated as Cronbach's alpha.
      Outcomes at 2 weeks were; satisfaction with care (5-point Likert scale
      dichotomised into yes/no) and ability to control pain (0-10). Associations of the
      CRQ with patient characteristics and outcomes were determined in mixed models to
      account for dependency of observations within clinics. Results: From 964 patients
      visiting between November 2016 and October 2017 with new episodes of LBP, 717
      completed the CRQ with no more than 1% missing values on any single item. The
      internal consistency was acceptable for all subscales (0.67-0.86). Scores were
      generally high, and more so in patients visiting a chiropractor for the first
      time. All four subscales were positively associated with satisfaction (Odds
      ratios 1.08-1.23) and generic reassurance was weakly associated with pain control
      (beta = 0.07 [95% CI 0.03-0.11]). Conclusions: The CRQ was feasible for use in a
      Danish chiropractic setting and scores on all four reassurance subscales related
      positively to patients' satisfaction. Patients who had visited a chiropractor
      previously reported slightly lower levels of reassuring information, and it
      should be explored if this is in accordance with the patients' needs. The
      potential impact on patient outcomes needs investigation.

PMID- 30181867
TI  - Epidemiology and risk factors for bipolar disorder.
AB  - Bipolar disorder is a multifactorial illness with uncertain aetiology. Knowledge
      of potential risk factors enables clinicians to identify patients who are more
      likely to develop bipolar disorder, which directs further investigation, follow
      up and caution when prescribing. Ideally, identifying directly causative factors
      for bipolar disorder would enable intervention on an individual or population
      level to prevent the development of the illness, and improve outcomes through
      earlier treatment. This article reviews the epidemiology of bipolar disorder,
      along with putative demographic, genetic and environmental risk factors, while
      assessing the strength of these associations and to what extent they might be
      said to be 'causative'. While numerous genetic and environmental risk factors
      have been identified, the attributable risk of individual factors is often small,
      and most are not specific to bipolar disorder but are associated with several
      mental illnesses. Therefore, while some genetic and environmental factors have
      strong evidence supporting their association with bipolar disorder, fewer have
      sufficient evidence to establish causality. There is increasing interest in the
      role of specific gene-environment interactions, as well as the mechanisms by
      which risk factors interact to lead to bipolar disorder.

PMID- 30181869
TI  - Rationale and development of a business case for antimicrobial stewardship
      programs in acute care hospital settings.
AB  - Background: Antimicrobial stewardship programs (ASPs) have been shown to reduce
      inappropriate antimicrobial use and its consequences. However, these programs
      lack legislative requirements in many places and it can be difficult to determine
      what human resources are required for these programs and how to create a business
      case to present to hospital administrators for program funding. The objectives of
      the current paper were to review legislative requirements and outline human
      resource requirements for ASPs, and to create a base business case for ASPs.
      Methods: A working group of antimicrobial stewardship experts from across Canada
      met to discuss the necessary components for creation of a business case for
      antimicrobial stewardship. A narrative review of the literature of the regulatory
      requirements and human resource recommendations for ASPs was conducted. Informed
      by the review and using a consensus decision-making process, the expert working
      group developed human resource recommendations based on a 1000 bed acute care
      health care facility in Canada. A spreadsheet based business case model for ASPs
      was also created. Results: Legislative and /or regulatory requirements for ASPs
      were found in 2 countries and one state jurisdiction. The literature review and
      consensus development process recommended the following minimum human resources
      complement: 1 physician, 3 pharmacists, 0.5 program administrative and
      coordination support, and 0.4 data analyst support as full time equivalents
      (FTEs) per 1000 acute care beds. Necessary components for the business case
      model, including the human resource requirements, were determined to create a
      spreadsheet based model. Conclusions: There is evidence to support the negative
      outcomes of inappropriate antimicrobial use as well as the benefits of ASPs.
      Legislative and /or regulatory requirements for ASPs are not common. The
      available evidence for human resource recommendations for ASPs using a narrative
      review process was examined and a base business case modelling scenario was
      created. As regulatory requirements for ASPs increase, it will be necessary to
      create accurate business cases for ASPs in order to obtain the necessary funding
      to render these programs successful.

PMID- 30181870
TI  - Characteristics of glycopeptide-resistant Staphylococcus aureus strains isolated
      from inpatients of three teaching hospitals in Warsaw, Poland.
AB  - Background: Vancomycin is still one of the most commonly used drug for treatment
      of severe methicillin-resistant Staphylococcus aureus (MRSA) infections.
      Vancomycin-resistant S. aureus (VRSA) strains are a serious danger for public
      health. This study aimed to characterize healthcare-associated MRSA (HA-MRSA)
      strains, resistant to at least one of glycopeptide antibiotics: vancomycin (VRSA)
      and/or teicoplanin (TRSA), isolated at three Warsaw hospitals over a period of 17
      years (1991-2007). Methods: Among 600 HA-MRSA strains, isolated from patients
      with symptomatic infections, 47 were subjected to detailed analysis. In the
      study, mechanisms behind VRSA phenotypes were determined (E-tests, GRD-test, agar
      dilution method and vanA/B detection). Characteristics of selected isolates on
      molecular level: i) by detection of resistance genes ermA/ermB/ermC, msrA/msrB,
      linA/linA', aacA-aphD, aadD, aph(3")-IIIa; ii) SCCmec-typing and iii) MLST-typing
      was done. Results: In general population of studied strains, 11/47 (23.4%) were
      VRSA and 36/47 (76.6%) were resistant only to teicoplanin. All isolates exhibited
      van-independent mechanisms of resistance. Over 80% of isolates belonged to clonal
      complex CC8, with the following predominant sequence types (STs)/clones: ST247
      IA/Iberian, ST241-III/Finland-UK, and ST239-III/Brazilian. Most of the isolated
      strains harboured ermA and aacA-aphD genes, encoding additional resistance to
      macrolides, lincosamides, streptogramin B, and majority of aminoglycosides. They
      occurred also in Polish VRSA/TRSA population over the period, which was subjected
      for analysis: an increase in MIC values for glycopeptides, evolution in terms of
      the level and extent of resistance, and genetic re-assortment in epidemic clones.
      Conclusions: VRSA strains isolated from patients hospitalized at three Warsaw
      teaching hospitals in Poland, over a period of 17-years do not pose a threat as
      potential donors of van genes in horizontal-gene transfer processes, but are
      constantly evolving and represent international epidemic clones.

PMID- 30181871
TI  - Post hepatectomy liver failure - A comprehensive review of current concepts and
      controversies.
AB  - Post hepatectomy liver failure (PHLF) comprises of a conundrum of symptoms and
      signs following major hepatic resections. The pathophysiology essentially
      revolves around disruption of the normal hepatocyte regeneration and disturbed
      liver homeostasis. Prompt identification of the pre-operative predictors of PHLF
      in the form of biochemical parameters and imaging features are of paramount
      importance for any hepatic surgeon and forms the cornerstone of its management.
      Treatment revolves around a goal-directed resuscitation of the systemic organ
      failure. Auxiliary support systems such as liver dialysis devices and stem cell
      therapy are still under investigational trials for treatment of the same.
      Orthotopic liver transplantation (OLT) is the last resort in most cases not
      responding to other measures.

PMID- 30181872
TI  - Transection of the appendix and omentum following a seat belt injury; case report
      and literature review.
AB  - Introduction: Appendiceal injuries following a blunt abdominal trauma are rare.
      Upon literature review, several cases have been reported to develop appendicitis
      following blunt abdominal trauma, but total transection of the appendix is
      extremely rare. Case presentation: Our case involves a 24-year-old male
      restrained driver who was involved in a motor vehicle accident. He had bruising
      corresponding to the pattern of the seatbelt, the 'seatbelt sign', on admission.
      On his second day of admission, he was found to have a rigid abdomen. On
      exploratory laparotomy, the patient had a completely transected appendix with a
      10 * 10 cm piece of transected omentum lying in the pelvic cavity. Discussion:
      Literature suggests that seat belts may play a role in the mechanism of injury
      leading to transection. Conclusion: Since the introduction of seatbelt in the
      1970s, fatalities from road traffic accidents have fallen by up to 60%. However,
      the seat belt itself is associated with a unique injury profile, including
      intestinal tears, perforations, and transections, collectively termed "the
      seatbelt syndrome". Seat belt syndrome injuries may sometimes have a delayed
      presentation, thus repeated abdominal examination is recommended even if the
      patient is initially stable. Appendiceal transection is rare but may occur. A
      thorough inspection of the abdominal soft tissue to look for accompanying
      injuries is important if case an exploratory laparotomy is warranted.

PMID- 30181873
TI  - Activation of pro-survival metabolic networks by 1,25(OH)2D3 does not hamper the
      sensitivity of breast cancer cells to chemotherapeutics.
AB  - Background: We have previously identified 1,25-dihydroxyvitamin D3 [1,25(OH)2D3],
      the bioactive form of vitamin D3, as a potent regulator of energy-utilization and
      nutrient-sensing pathways in prostate cancer cells. In the current study, we
      investigated the effects of 1,25(OH)2D3 on breast cancer (BCa) cell metabolism
      using cell lines representing distinct molecular subtypes, luminal (MCF-7 and T
      47D), and triple-negative BCa (MDA-MB-231, MDA-MB-468, and HCC-1143). Methods:
      1,25(OH)2D3's effect on BCa cell metabolism was evaluated by employing a
      combination of real-time measurements of glycolysis/oxygen consumption rates
      using a biosensor chip system, GC/MS-based metabolomics, gene expression
      analysis, and assessment of overall energy levels. The influence of treatment on
      energy-related signaling molecules was investigated by immunoblotting. Results:
      We show that 1,25(OH)2D3 significantly induces the expression and activity of the
      pentose phosphate pathway enzyme glucose-6-phosphate dehydrogenase (G6PD) in all
      BCa cell lines, however differentially influences glycolytic and respiratory
      rates in the same cells. Although 1,25(OH)2D3 treatment was found to induce
      seemingly anti-oxidant responses in MCF-7 cells, such as increased intracellular
      serine levels, and reduce the expression of its putative target gene thioredoxin
      interacting protein (TXNIP), intracellular reactive oxygen species levels were
      found to be elevated. Serine accumulation in 1,25(OH)2D3-treated cells was not
      found to hamper the efficacy of chemotherapeutics, including 5-fluorouracil.
      Detailed analyses of the nature of TXNIP's regulation by 1,25(OH)2D3 included
      genetic and pharmacological inhibition of signaling molecules and metabolic
      enzymes including AMP-activated protein kinase and G6PD, as well as by studying
      the ITCH (E3 ubiquitin ligase)-TXNIP interaction. While these investigations
      demonstrated minimal involvement of such pathways in the observed non-canonical
      regulation of TXNIP, inhibition of estrogen receptor (ER) signaling by tamoxifen
      mirrored the reduction of TXNIP levels by 1,25(OH)2D3, demonstrating that the
      latter's negative regulation of ER expression is a potential mechanism of TXNIP
      modulation. Conclusions: Altogether, we propose that regulation of energy
      metabolism contributes to 1,25(OH)2D3's anti-cancer effects and that combining
      1,25(OH)2D3 with drugs targeting metabolic networks in tumor cells may lead to
      synergistic effects.

PMID- 30181874
TI  - Fidelity monitoring in complex interventions: a case study of the WISE
      intervention.
AB  - Background: Researchers face many decisions in developing a measurement tool and
      protocol for monitoring fidelity to complex interventions. The current study uses
      data evaluating a nutrition education intervention, Together, We Inspire Smart
      Eating (WISE), in a preschool setting to explore issues of source, timing, and
      frequency of fidelity monitoring. Methods: The overall study from which these
      data are drawn was a pre/post design with an implementation-focused process
      evaluation. Between 2013 and 2016, researchers monitored fidelity to evidence
      based components of the WISE intervention in 49 classrooms in two Southern
      states. Data collectors obtained direct assessment of fidelity on a monthly basis
      in study classrooms. Research staff requested that educators provide indirect
      assessment on a weekly basis. We used mean comparisons (t-tests), correlations
      (Pearson's r), and scatterplots to compare the direct and indirect assessments.
      Results: No mean comparisons were statistically different. Correlations of direct
      and indirect assessments of the same component for the same month ranged between 
      0.51 (p = 0.01) and 0.54 (p = 0.001). Scatterplots illustrate that negative
      correlations can be driven by individuals who are over reporting (i.e., self
      report bias) and that near zero correlations approximate the ideal situation
      (i.e., both raters identify high fidelity). Conclusion: Our findings illustrate
      that, on average, observed and self-reports may seem consistent despite weak
      correlations and individual cases of extreme over reporting by those implementing
      the intervention. The nature of the component to which fidelity is being
      monitored as well as the timing within the context of the intervention are
      important factors to consider when selecting the type of assessment and frequency
      of fidelity monitoring. Trial registration: NCT03075085 Registered 20 February
      2017. Trial registration corresponds to the funding that supported the writing of
      this manuscript, not the data collection. The original study was not a trial and
      was collected without registration. However, the data reported here provided
      foundational preliminary data for the trial.

PMID- 30181875
TI  - Mid-Upper Arm Circumference (MUAC) shows strong geographical variations in
      children with edema: results from 2277 surveys in 55 countries.
AB  - Background: Severe acute malnutrition (SAM) is defined by a mid-upper arm
      circumference (MUAC) less than 115 mm or a weight-for-height z-score (WHZ) less
      than - 3 but also by the presence of bilateral pitting edema, also known as
      kwashiorkor or edematous malnutrition. Although edematous malnutrition is a life
      threatening condition, it has not been prioritized in recent research and has
      been neglected in global health initiatives. Methods: Two thousand two hundred
      and seventy-seven survey datasets were collected, and the age, sex, weight,
      height, MUAC and the presence or absence of edema were analyzed for more than 1.7
      million children of 6-59 months from 55 countries, covering the period of 1992 to
      2015. Results: During the last 10 years, the prevalence of nutritional edema was
      estimated at less than 1% in most of the countries where data were available.
      Some countries in Central and South Africa, as well as Haiti in the Caribbean,
      reported higher prevalence, and Yemen, Zimbabwe and the Democratic Republic of
      Congo reported prevalence between 1 and 2%. Surveys from a significant number of
      countries in Africa indicated that more than a third of SAM cases defined by MUAC
      < 115 mm had edema, including Malawi, Rwanda, Zambia, Togo and Cameroon. Children
      with edema were consistently shown across various analyses to have a
      significantly lower median MUAC than children without edema. However, the MUAC
      distribution had a large spread, with many children with edema having a MUAC >
      115 mm, and this varied widely between countries, with median MUAC in edematous
      children ranging from 102 mm (Mali) to 162 mm (Sri Lanka). The proportion of SAM
      children with edema was found to be higher for older children. Conclusions: This
      study provides the most recent geographical distribution of nutritional edema and
      demonstrates that edema is a common manifestation of SAM, mainly occurring in
      Central Africa. The associated nutritional status, as assessed by MUAC, shows
      strong variation among children with edema. A more systematic and standardized
      system is required to collect data on edema in order to facilitate prevention,
      screening, referral and treatment of edematous malnutrition.

PMID- 30181876
TI  - Post marketing study of hemodynamic and hematological noninvasive readings in a
      blood bank.
AB  - Objectives: This validation test was conducted in the Fujisan Blood Bank,
      Fortaleza, Brazil and evaluated the noninvasive TensorTip MTX (MTX, Cnoga Medical
      Ltd.) readings of hemoglobin, hematocrit, red blood cells, blood pressure, and
      heart rate compared to reference lab device readings. Generally, these parameters
      are measured from venous or capillary blood samples run on a laboratory analyzer
      or handheld invasive testing devices. Needle sticks are inconvenient to blood
      donors with relatively high exposure risks. To our vision, noninvasive
      determination would be of benefit to blood contributors and medical professional
      teams; it would be fast and painless. Methods: A total of 334 subjects were
      included in the Fujisan blood bank validation (65% male, 35% female). Hemoglobin,
      hematocrit, and red blood cells, as well as blood pressure and heart rate, were
      measured noninvasively using the MTX device and were compared to venous blood
      samples run on two laboratory hematology analyzers (Horiba ABX Micros60 and
      Siemens blood count analyzer), to digital sphygmomanometer (OMRON BP786) and to
      manual auscultation. The noninvasive measurement with the appropriate virtual arm
      cuff setting was performed simultaneously with the blood sample extraction of the
      reference devices measurement. Results: There was no statistically significant
      difference (p > 0.05, paired, two-tailed t-test) between the average daily
      hemoglobin, hematocrit, and red blood cells measurements provided by the MTX
      device and the laboratory hematology analyzer. In addition, there was no
      significant difference between the daily blood pressure and heart rate results
      provided by the MTX device and the digital and manual sphygmomanometers. The
      error calculated between the MTX and the reference device was found to be
      sufficiently accurate according to the relevant standards. Conclusion: The MTX
      accuracy of noninvasive hemoglobin, hematocrit, red blood cells, blood pressure,
      and heart rate measurements satisfies the industrial standards; therefore, the
      device enables more accurate, efficient, and effective patient care.

PMID- 30181877
TI  - Impact of symptom bilaterality and hand dominance on patient-reported disability
      outcomes.
AB  - Objectives: It is not clear if using patients with bilateral symptoms would
      impact the level of disability reported in orthopaedic research. The purposes of
      this study were to (1) examine the prevalence of bilateral shoulder symptoms
      (significant pain, stiffness or weakness affecting function) in patients with
      rotator cuff impingement syndrome, rotator cuff tear and osteoarthritis of the
      glenohumeral joint, (2) explore risk factors associated with bilateral shoulder
      symptoms, and (3) examine the impact of symptom bilaterality and hand dominance
      on pre- and post-operative patient-oriented disability outcomes. Methods: This
      study involved secondary analysis of prospectively collected data of patients who
      had undergone shoulder surgery and had returned for their 1-year follow-up. Two
      outcome measures were collected prior to surgery and at 1-year following surgery:
      the American Shoulder and Elbow Surgeons and the Constant-Murley Score. Results:
      Data of 772 patients, 376 (49%) females, 396 males (51%); 288 (impingement
      syndrome), 332 (rotator cuff tear), and 152 (osteoarthritis) were included in the
      analysis. There was a statistically significant difference in the prevalence of
      bilateral symptoms being 44%, 28%, and 22% in the osteoarthritis, impingement
      syndrome, and rotator cuff tear groups, respectively (p < 0.0001). The prevalence
      of dominant side involvement was 71%, 67%, and 53% in the rotator cuff tear,
      impingement syndrome, and osteoarthritis groups (p < 0.0001). Older age and
      female sex were risk factors for development of bilateral symptoms only in
      patients with rotator cuff tear. Neither symptom bilaterality nor dominant arm
      involvement had a negative impact on patient-oriented disability outcome measures
      prior to or after surgery (p > 0.05). Conclusion: This study shows that patients
      with osteoarthritis of the glenohumeral joint have the highest prevalence of
      bilateral shoulder complaints. The older age and the female sex increased the
      risk of having bilateral symptoms in patients with rotator cuff tear. Having
      bilateral shoulder symptoms or dominant side involvement was not associated with
      higher level of disability prior or after surgery.

PMID- 30181878
TI  - Radar quantifies migrant concentration and Dawn reorientation at a Great Lakes
      shoreline.
AB  - Background: Millions of flying migrants encounter the Great Lakes and other large
      water bodies on long-distance flights each spring and fall, but quantitative data
      regarding how they traverse these obstacles are limited. Shorelines are known
      areas of migrant concentration due to the ecological barrier effect, but details
      on the magnitude of this concentration and the flight behaviors causing it are
      largely unknown and difficult to quantify. Mobile avian radar can provide a
      unique view of how birds and bats move across landscapes by tracking thousands of
      individual migrants moving through a sample volume that extends multiple
      kilometers in radius. Results: During the spring of 2014 we used two avian radar
      units to compare migration patterns at shoreline (1.5 km from the shore) and
      inland (20 km from the shore) sites along the eastern shoreline of Lake Michigan
      in the north-central US. We found shoreline activity to be 27% greater than
      inland activity over all time periods, and 132% greater during the hour
      surrounding dawn. An analysis of flight directions found that migrants flew to
      the north and northwest during dusk and night, with many heading out over the
      lake, but shifted direction towards the east at dawn, as those flying over water
      reoriented towards land. This shift in direction, which was most intense at the
      shoreline, may contribute to the higher concentrations of migrants observed at
      shorelines in this study and others. Conclusions: These findings help confirm and
      quantify the phenomenon of nocturnal migrant reorientation at dawn, and also
      stress the functional importance of coastal regions for aerial migrants. The high
      use of coasts by migrants highlights the importance of conserving shoreline
      stopover habitat, which often competes with anthropogenic uses. We suggest using
      a high degree of caution when assessing potential impacts from development in
      these sensitive environments, and encourage protection of these high-use areas.

PMID- 30181879
TI  - Pericardial injury from chest compression: a case report of incidental release of
      cardiac tamponade.
AB  - Background: Although chest compression is a standard technique in cardiopulmonary
      resuscitation, it is well recognized that manual chest compression causes various
      internal injuries, of which major injuries are often fatal. Similarly, when
      cardiac tamponade occurs in patients with type A acute aortic dissection, many
      patients die before reaching the hospital. We report a rare case in which chest
      compressions caused pericardial laceration that may have inadvertently played a
      life-saving role in releasing cardiac tamponade induced by acute aortic
      dissection. Case presentation: A 67-year-old woman developed cardiac arrest soon
      after complaining of epigastric pain, and after successful resuscitation by
      manual chest compression, she was transferred to our hospital. On arrival, the
      patient was 14 on the Glasgow Coma Scale. An ECG showed a normal sinus rhythm,
      and no arrhythmias or signs of myocardial ischemia were observed. A chest X-ray
      revealed left pleural effusion, while cardiomegaly and pneumothorax were not
      identified. Computed tomography revealed type A aortic dissection, mild
      pericardial effusion, and massive left pleural effusion. No pulmonary embolus was
      found on the CT. After drainage of bloody effusion from the left pleural space,
      an emergency operation was begun. During surgery, a pericardial laceration with
      communication to the left pleural space and a hemothorax were found; however, no
      cardiac injury was identified. No other intra-thoracic injuries or rupture of the
      aortic dissection causing the hemothorax were detected. Hemiarch replacement was
      performed without difficulty, but the patient died of multi-organ failure 30 days
      after surgery. Conclusions: We report a case of pericardial injury without
      skeletal fracture caused by chest compression. The pericardial laceration may
      have inadvertently served to release the cardiac tamponade induced by the acute
      aortic dissection, resulting in the hemothorax, and provided time to receive
      surgery.

PMID- 30181880
TI  - Transient hyperlactatemia during intravenous administration of glycerol: a
      prospective observational study.
AB  - Background: Intravenous glycerol treatment, usually administered in the form of a
      5% fructose solution, can be used to reduce intracranial pressure. The
      administered fructose theoretically influences blood lactate levels, although
      little is known regarding whether intravenous glycerol treatment causes transient
      hyperlactatemia. This study aimed to evaluate blood lactate levels in patients
      who received intravenous glycerol or mannitol. Methods: This single-center
      prospective observational study was performed at a 14-bed general intensive care
      unit between August 2016 and January 2018. Patients were excluded if they were <
      20 years old or had pre-existing hyperlactatemia (blood lactate > 2.0 mmol/L).
      The included patients received intravenous glycerol or mannitol to reduce
      intracranial pressure and provided blood samples for lactate testing before and
      after the drug infusion (before the infusion and after 15 min, 30 min, 45 min, 60
      min, 90 min, 120 min, and 150 min). Results: Among the 33 included patients, 13
      patients received 200 mL of glycerol over 30 min, 13 patients received 200 mL of
      glycerol over 60 min, and 7 patients received 300 mL of mannitol over 60 min.
      Both groups of patients who received glycerol had significantly higher lactate
      levels than the mannitol group (2.8 mmol/L vs. 2.2 mmol/L vs. 1.6 mmol/L, P <
      0.0001), with the magnitude of the increase in lactate levels corresponding to
      the glycerol infusion time. There were no significant inter-group differences in
      cardiac index, stroke volume, or stroke volume variation. In the group that
      received the 30-min glycerol infusion, blood lactate levels did not return to the
      normal range until after 120 min. Conclusions: Intravenous administration of
      glycerol leads to higher blood lactate levels that persist for up to 120 min.
      Although hyperlactatemia is an essential indicator of sepsis and/or impaired
      tissue perfusion, physicians should be aware of this phenomenon when assessing
      the blood lactate levels.

PMID- 30181881
TI  - Useful clinical features and hematological parameters for the diagnosis of dengue
      infection in patients with acute febrile illness: a retrospective study.
AB  - Background: Dengue infection patients are presented with acute febrile illness.
      Clinical presentations may mimic other infections. The serology for definite
      diagnosis is costly and inaccessible in many hospitals. We sought to identify the
      clinical features and hematologic parameters from a complete blood count (CBC)
      which distinguish dengue infection from other causes. Methods: This was a
      retrospective single center study from Chiang Mai University Hospital. All
      patients who presented with acute fever between September 2013 and July 2015 were
      included. The diagnosis of dengue infection must be confirmed by serology. The
      control groups were patients who presented with acute febrile illness without
      localizing signs. Clinical data and CBC results were reviewed and compared. The
      Chi-square test was used to compare categorical variables. The CBC parameters
      were analyzed using the linear mixed model. Results: One hundred and fifty-four
      dengue and 146 control patients were included. Headache, nausea, loss of appetite
      and bleeding diathesis were significantly symptoms in dengue patients (p < 0.05).
      There was some diversity in the the CBC in the dengue patients compared to the
      control group. Moreover, this study also identified the day of fever which these
      parameters were statistically significant. The dengue group had higher hemoglobin
      and hematocrit from day 3 to day 10 (p < 0.001), lower white blood cell count
      from day 1 to day 10 (p < 0.001), lower platelet count from day 3 to day 10 (p <
      0.001), higher monocyte on day 1-4 (p < 0.001), higher atypical lymphocyte
      percentage on day 5-9 (p < 0.001) and higher eosinophil percentage on day 9-10 (p
      = 0.001). Furthermore, the neutrophil to lymphocyte percentage ratio of dengue
      group was > 1 on the first 5 days then reversed on day 6 to Day 9 but in non
      dengue group, the ratio was always > 1. Conclusion: We identified important
      clinical features and CBC parameters to differentiate dengue patients from other
      patients who had acute febrile illness from other causes. This identification
      could be done in local hospitals to give an accurate diagnosis, enabling further
      investigation to be tailored and treatment commenced earlier.

PMID- 30181882
TI  - Changes of depression and job stress in workers after merger without downsizing.
AB  - Background: Since the 1980s, restructuring, which includes downsizing, closures,
      mergers, and privatization, has expanded worldwide, and various studies have
      investigated its effect on health. However, previous studies have mainly focused
      on restructuring accompanied by massive lay-offs, and the effect of a merger on
      workers' health is still controversial. This study aims to investigate changes in
      worker depression and job stress after a merger without downsizing, which is
      unusual in Korea. Methods: Repeated surveys were done in April 2014, April 2015,
      and April 2016 involving the participation of 209 subjects. Participants were
      divided into two groups, which were comprised of blue-collar workers (104) and
      white-collar workers (105). Sociodemographic characteristics, including age,
      education level, job tenure, gender, marital status, smoking status, and alcohol
      consumption, were measured via a survey. To determine the level of depression,
      the Korean version of the Center for Epidemiologic Studies Depression Scale (CES
      D) was employed, and to investigate job stress, the Korean Occupational Stress
      Scale-Short Form (KOSS-SF) was used. For statistical analyses, Pearson's chi
      square test, the Student's t-test, and repeated measure analysis of variance
      (ANOVA) were performed. Results: The results showed that depression (CES-D, F[2,
      400] = 0.466, p = 0.628) was changed but without significance and job stress
      (KOSS-SF, F[1.899, 379.831] = 3.192, p = 0.045) were significantly different. The
      between-group difference in the CES-D score between the blue- and white-collar
      workers by survey administration time was not statistically significant (F =
      0.316, p = 0.574). The interaction between the survey time and occupational group
      was also not statistically significant (F = 0.967, p = 0.381). The between-group
      difference in the KOSS-SF total score was not statistically significant (F =
      1.132, p = 0.289), and the interaction between the survey administration time and
      occupational group was also not significant (F = 0.817, p = 0.437). In the job
      stress subgroup analyses Job insecurity and Lack of reward showed a significant
      difference by survey administration time. Conclusion: This study showed that a
      merger without massive downsizing can cause negative health effects such as an
      changes in depression and increase in job stress. To improve the health of
      workers, both the immediate negative effects on health, and the long-term effects
      or their resolution over time should be considered prior to the merger.

PMID- 30181883
TI  - Performance assessment on the Korean Computerized Neurobehavioral Test using a
      mobile device and a conventional computer: an experimental study.
AB  - Background: The Korean Computerized Neurobehavioral Test (KCNT) is a
      psychological assessment tool used as part of Workers' Special Health
      Examinations in Korea. Due to the spread of mobile technology, this study aimed
      to compare results of the KCNT administered on a tablet PC versus a desktop
      computer, and, therefore, assess the clinical applicability of mobile devices.
      Methods: A total of 72 participants enrolled in this study. Their age, sex, and
      years of formal education were collected during an interview, as well as their
      typing speed. The test battery comprised five subtests: Simple Reaction Time
      test, Choice Reaction Time test, Digit Addition test, Symbol-Digit Substitution
      test, and Finger Tapping Speed test. Participants repeated the KCNT test battery
      in a randomly assigned order using four different testing systems: a desktop
      computer equipped with a conventional 106-key keyboard (System 1), a desktop
      computer equipped with a simplified keyboard (System 2), a tablet PC with a
      simplified 17-key on-screen keyboard (System 3), and a tablet PC equipped with a
      simplified keyboard (System 4). Results: Results of the Digit Addition test did
      not differ significantly for different testing systems. In contrast, results of
      the Simple Reaction Time test, Choice Reaction Time test, Symbol-Digit
      Substitution test, and Finger Tapping test were lower for the tablet PC (Systems
      3 and 4) compared to the desktop computer (Systems 1 and 2). Systems 1 and 2 did
      not show significantly different results. Performance on System 3 was inferior to
      that on System 4, only for the Choice Reaction Time test and Finger Tapping Speed
      test. There were also significant differences in performance by computer
      familiarity when adjusted for age and education; however, the performance of each
      group on the test systems showed similar patterns. Conclusions: It is not
      recommended to use a tablet PC to administer the KCNT to evaluate neurobehavioral
      performance for the Simple Reaction Time test and Choice Reaction Time test;
      however, tablet PCs with an on-screen keyboard may be used to perform the Digit
      Addition test, and the Symbol-Digit Substitution test and Finger Tapping Speed
      test to a limited degree.

PMID- 30181884
TI  - The effect of increasing the illumination on operators' visual performance in the
      control-room of a combined cycle power plant.
AB  - Background: Lighting is one of the environmental factors affecting the
      performance of the control room operators. Therefore, the aim of this study was
      to compare the control room operators' visual performance in two different
      illumination conditions at a combined cycle power plant through field-work.
      Methods: Sixteen operators in day shift were evaluated with the Freiburg Visual
      Acuity test (FrACT) software at two lighting systems with different intensities.
      It includes the first phase with fluorescent illumination system (Power: 40 W,
      Color Temperature: 4000 Kelvin, Luminous Flux: 2780 Lumen and Model: Pars Shahab)
      and the second phase with a combined illumination system includes fluorescent and
      LED (Power: 48 W, Color Temperature: 4000 Kelvin, Luminous Flux: 5400 Lumen and
      Model: Mazinoor). Results: Based on the results, visual performance index and
      visual acuity significantly increased after the intervention (p < 0.001). As to
      contrast, more lighting significantly reduced the percentage of recognized
      contrast (p < 0.001) and increased the contrast performance index (p < 0.001).
      Conclusions: The results of this study showed that increasing the intensity of
      light from the values below the allowable limit to the values above the allowable
      limit would increase the visual indicators in individuals.

PMID- 30181885
TI  - First genetic linkage map of Lathyrus cicera based on RNA sequencing-derived
      markers: Key tool for genetic mapping of disease resistance.
AB  - The Lathyrus cicera transcriptome was analysed in response to rust (Uromyces
      pisi) infection to develop novel molecular breeding tools with potential for
      genetic mapping of resistance in this robust orphan legume species. One RNA-seq
      library each was generated from control and rust-inoculated leaves from two L.
      cicera genotypes with contrasting quantitative resistance, de novo assembled into
      contigs and sequence polymorphisms were identified. In toto, 19,224 SNPs
      differentiate the susceptible from the partially resistant genotype's
      transcriptome. In addition, we developed and tested 341 expressed E-SSR markers
      from the contigs, of which 60.7% varied between the two L. cicera genotypes. A
      first L. cicera linkage map was created using part of the developed markers in a
      RIL population from the cross of the two genotypes. This map contains 307
      markers, covered 724.2 cM and is organised in 7 major and 2 minor linkage groups,
      with an average mapping interval of 2.4 cM. The genic markers also enabled us to
      compare their position in L. cicera map with the physical position of the same
      markers mapped on Medicago truncatula genome, highlighting a high macrosyntenic
      conservation between both species. This study provides a large new set of genic
      polymorphic molecular markers with potential for mapping rust resistances. It
      represents the first step towards genomics-assisted precision breeding in L.
      cicera.

PMID- 30181886
TI  - Infection of post-harvest peaches by Monilinia fructicola accelerates sucrose
      decomposition and stimulates the Embden-Meyerhof-Parnas pathway.
AB  - To study the changes in sugar metabolism caused by fungal infection in post
      harvest peaches, fruit from two cultivars ('Baifeng' and 'Yulu') was inoculated
      with Monilinia fructicola and stored at 10  degrees C. During disease
      development, soluble sugar content was monitored, as well as the activities and
      expression of selected enzymes. Disease progression was accompanied by a decrease
      in sucrose content and increases in reducing sugars and soluble solids,
      consistent with higher enzyme activities for acid invertase, neutral invertase
      and sucrose synthase-cleavage, and lower activities for sucrose synthase
      synthesis and sucrose phosphate synthase. Activities of phosphofructokinase,
      hexokinase, and pyruvate kinase, which are related to hexose metabolism, also
      increased. These changes stimulate the Embden-Meyerhof-Parnas (EMP) pathway. We
      conclude that the fungal disease in peach fruit accelerates the decomposition of
      sucrose, thereby providing more glucose as a substrate to the EMP pathway.

PMID- 30181888
TI  - An AGAMOUS-like factor is associated with the origin of two domesticated
      varieties in Cymbidium sinense (Orchidaceae).
AB  - Cymbidium has been artificially domesticated for centuries in Asia, which
      produced numerous cultivated varieties. Flowers with stamenoid tepals or those
      with multiple tepals have been found in different species of Cymbidium; however,
      the molecular basis controlling the formation of these phenotypes is still
      largely unknown. Previous work demonstrated that AGAMOUS/AG lineage MADS genes
      function in floral meristem determinacy as well as in reproductive organs
      development in both dicots and monocots, indicating a possible relationship with
      the origin of two flower varieties in Cymbidium. Here, we characterized and
      analyzed two AG lineage paralogues, CsAG1 and CsAG2, from Cymbidium sinense, both
      of which were highly expressed in the gynostemium column of a standard C.
      sinense. Interestingly, we detected ectopic expression of CsAG1 rather than CsAG2
      in all floral organs of a stamenoid-tepal variety and significant down-regulation
      of CsAG1 in a variety with multiple tepals. Over-expression of CsAG1 in wild type
      Arabidopsis resulted in petal-to-stamen homeotic conversion, suggesting a
      conserved C-function of CsAG1 in the development of Cymbidium flower. Altogether,
      our results supported a hypothesis that disruption of a single AG-like factor
      would be associated with the formation of two domesticated varieties in C.
      sinense.

PMID- 30181887
TI  - Using light to improve commercial value.
AB  - The plasticity of plant morphology has evolved to maximize reproductive fitness
      in response to prevailing environmental conditions. Leaf architecture elaborates
      to maximize light harvesting, while the transition to flowering can either be
      accelerated or delayed to improve an individual's fitness. One of the most
      important environmental signals is light, with plants using light for both
      photosynthesis and as an environmental signal. Plants perceive different
      wavelengths of light using distinct photoreceptors. Recent advances in LED
      technology now enable light quality to be manipulated at a commercial scale, and
      as such opportunities now exist to take advantage of plants' developmental
      plasticity to enhance crop yield and quality through precise manipulation of a
      crops' lighting regime. This review will discuss how plants perceive and respond
      to light, and consider how these specific signaling pathways can be manipulated
      to improve crop yield and quality.

PMID- 30181889
TI  - VlbZIP30 of grapevine functions in dehydration tolerance via the abscisic acid
      core signaling pathway.
AB  - Drought stress limits the growth and development of grapevines, thereby reducing
      productivity, but the mechanisms by which grapevines respond to drought stress
      remain largely uncharacterized. Here, we characterized a group A bZIP gene from
      "Kyoho" grapevine, VlbZIP30, which was shown to be induced by abscisic acid (ABA)
      and dehydration stress. Overexpression of VlbZIP30 in transgenic Arabidopsis
      thaliana enhanced dehydration tolerance. Transcriptome analysis revealed that a
      major proportion of ABA-responsive and/or drought-responsive genes are
      transcriptionally regulated by VlbZIP30 during ABA or mannitol treatment at the
      cotyledon greening stage. We identified an A. thaliana G-box motif (CACGTG) and a
      potential grapevine G-box motif (MCACGTGK) in the promoters of the 39 selected A.
      thaliana genes upregulated in the transgenic plants and in the 35 grapevine
      homologs, respectively. Subsequently, using two grapevine-related databases, we
      found that 74% (23/31) and 84% (21/25) of the detected grapevine genes were
      significantly upregulated by ABA and drought stress, respectively, suggesting
      that these genes are involved in ABA or dehydration stress and may be regulated
      by VlbZIP30 in grapevine. We propose that VlbZIP30 functions as a positive
      regulator of dehydration-responsive signaling in the ABA core signaling pathway.

PMID- 30181890
TI  - Tomato DCL2b is required for the biosynthesis of 22-nt small RNAs, the resulting
      secondary siRNAs, and the host defense against ToMV.
AB  - The tomato encode four functional DCL families, of which DCL2 is poorly studied.
      Here, we generated loss-of-function mutants for a tomato DCL2 gene, dcl2b, and we
      identified its major role in defending against tomato mosaic virus in relation to
      both natural and manual infections. Genome-wide small RNA expression profiling
      revealed that DCL2b was required for the processing 22-nt small RNAs, including a
      few species of miRNAs. Interestingly, these DCL2b-dependent 22-nt miRNAs
      functioned similarly to the DCL1-produced 22-nt miRNAs in Arabidopsis and could
      serve as triggers to generate a class of secondary siRNAs. In particular, the
      majority of secondary siRNAs were derived from plant defense genes when the
      plants were challenged with viruses. We also examined differentially expressed
      genes in dcl2b through RNA-seq and observed that numerous genes were associated
      with mitochondrial metabolism and hormone signaling under virus-free conditions.
      Notably, when the loss-of-function dcl2b mutant was challenged with tomato mosaic
      virus, a group of defense response genes was activated, whereas the genes related
      to lipid metabolism were suppressed. Together, our findings provided new insights
      into the roles of tomato DCL2b in small RNA biogenesis and in antiviral defense.

PMID- 30181891
TI  - Career choices for nephrology and factors influencing them: surveys of UK medical
      graduates.
AB  - Objectives: To study early and eventual career choices for nephrology among UK
      medical graduates and investigate factors which influenced career preferences.
      Design: Self-completed survey questionnaires mailed to medical graduates 1, 3, 5
      and 10 years after graduation. Setting: United Kingdom. Participants: UK medical
      graduates in 15 year-of-qualification cohorts between 1974 and 2015. Main outcome
      measures: Early career specialty choices, career specialty destinations at 10
      years and ratings of factors affecting career choices. Results: Around 0.4%-1.1%
      of these junior doctors expressed a career preference for nephrology, varying by
      year of qualification and years after qualification. Among all graduates of 1993
      2002 combined, 0.4% expressed a career preference for nephrology 1 year after
      qualification rising to 1.0% in year 5. Among graduates of 2005-2008, the
      corresponding figures were 1.0% in year 1 falling to 0.7% in year 5. Only 18% of
      doctors who chose nephrology in year 1 eventually became nephrologists. Of
      doctors who were practising as nephrologists for 10 years and more after
      qualification, 74% of the women and 56% of the men had decided to pursue a career
      in nephrology by year 5 after qualification. 'Enthusiasm/commitment' had a great
      deal of influence on those who chose nephrology, for all cohorts and all years
      studied. Conclusions: The most recent data suggest that the proportion of young
      doctors who sustain an interest in nephrology through the early postgraduate
      training years may be lower than among their predecessors. Efforts are needed to
      reverse the declining trend and increase interest in nephrology.

PMID- 30181892
TI  - Correction: Novel variants in COL4A4 and COL4A5 are rare causes of FSGS in two
      unrelated families.
AB  - [This corrects the article DOI: 10.1038/s41439-018-0016-8.].

PMID- 30181893
TI  - American psychologists, the Central Intelligence Agency, and enhanced
      interrogation.
AB  - In two commissioned articles, Health Psychology Open clarifies once and for all
      the role of two prominent American psychologists in the Central Intelligence
      Agency program of enhanced interrogation post 9/11. The Senate Select Committee
      on Intelligence Committee Study of the Central Intelligence Agency's Detention
      and Interrogation Program and the Hoffman Report produced more questions than
      answers. In these historically significant articles, Martin Seligman and Joseph
      Matarazzo assert the truth about their actions and the lessons learned.

PMID- 30181894
TI  - Hemophagocytic syndrome in a cat.
AB  - Case summary: A 12-year-old male castrated domestic shorthair cat was evaluated
      for a 10 month history of weight loss. Thin body condition and a grade II/VI
      systolic parasternal heart murmur was noted during examination. Moderate-to
      severe anemia and intermittent thrombocytopenia were identified on serial
      complete blood counts. Antibodies against feline immunodeficiency virus (FIV)
      were detected, but vaccination for FIV occurred previously. Echocardiography
      revealed biatrial and biventricular enlargement, left ventricular hypertrophy and
      pericardial effusion. Splenomegaly was present on abdominal ultrasound and
      cytological evaluation revealed macrophagic infiltration with
      erythrophagocytosis. Cytological evaluation of the bone marrow revealed similar
      findings. Histopathology of the spleen confirmed hemophagocytosis with no
      evidence of malignancy. A presumptive diagnosis of hemophagocytic syndrome was
      made. PCR testing for FIV on the splenic tissue was negative. The cat was treated
      with lomustine. Disease progression occurred approximately 6 months after
      diagnosis and the cat was euthanized. Relevance and novel information: To our
      knowledge, this is one of the few reports describing the diagnosis of
      hemophagocytic syndrome in a cat.

PMID- 30181895
TI  - Comparisons of gut microbiota profiles in wild-type and gelatinase B/matrix
      metalloproteinase-9-deficient mice in acute DSS-induced colitis.
AB  - Gut microbiota help to educate the immune system and a number of involved immune
      cells were recently characterized. However, specific molecular determinants in
      these processes are not known, and, reciprocally, little information exists about
      single host determinants that alter the microbiota. Gelatinase B/matrix
      metalloproteinase-9 (MMP-9), an innate immune regulator and effector, has been
      suggested as such a host determinant. In this study, acute colitis was induced in
      co-housed MMP-9-/- mice (n = 10) and their wild-type (WT) littermates (n = 10)
      via oral administration of 3% dextran sodium sulfate (DSS) for 7 days followed by
      2 days of regular drinking water. Control mice (10 WT and 10 MMP-9-/-) received
      normal drinking water. Fecal samples were collected at time of sacrifice and
      immediately frozen at -80  degrees C. Microbiota analysis was performed using 16S
      rRNA amplicon sequencing on Illumina MiSeq and taxonomic annotation was performed
      using the Ribosomal Database Project as reference. Statistical analysis
      correcting for multiple testing was done using R. No significant differences in
      clinical or histopathological parameters were found between both genotypes with
      DSS-induced colitis. Observed microbial richness at genus level and microbiota
      composition were not significantly influenced by host genotype. In contrast,
      weight loss, disease activity index, cage, and phenotype did significantly
      influence the intestinal microbiota composition. After multivariate analysis,
      cage and phenotype were identified as the sole drivers of microbiota composition
      variability. In conclusion, changes in fecal microbiota composition were not
      significantly altered in MMP-9-deficient mice compared to wild-type littermates,
      but instead were mainly driven by DSS-induced colonic inflammation.

PMID- 30181896
TI  - Growth hormone: isoforms, clinical aspects and assays interference.
AB  - The measurement of circulating concentrations of growth hormone (GH) is an
      indispensable tool in the diagnosis of both GH deficiency and GH excess. GH is a
      heterogeneous protein composed of several molecular isoforms, but the
      physiological role of these different isoforms has not yet been fully understood.
      The 22KD GH (22 K-GH) is the main isoform in circulation, followed by 20KD GH (20
      K-GH) and other rare isoforms. Studies have been performed to better understand
      the biological actions of the different isoforms as well as their importance in
      pathological conditions. Generally, the non-22 K- and 20 K-GH isoforms are
      secreted in parallel to 22 K-GH, and only very moderate changes in the ratio
      between isoforms have been described in some pituitary tumors or during exercise.
      Therefore, in a diagnostic approach, concentrations of 22 K-GH accurately reflect
      total GH secretion. On the other hand, the differential recognition of GH
      isoforms by different GH immunoassays used in clinical routine contributes to the
      known discrepancy in results from different GH assays. This makes the application
      of uniform decision limits problematic. Therefore, the worldwide efforts to
      standardize GH assays include the recommendation to use 22 K-GH specific GH
      assays calibrated against the pure 22 K-GH reference preparation 98/574. Adoption
      of this recommendation might lead to improvement in diagnosis and follow-up of
      pathological conditions, and facilitate the comparison of results from different
      laboratories.

PMID- 30181897
TI  - Draft genome of Dugesia japonica provides insights into conserved regulatory
      elements of the brain restriction gene nou-darake in planarians.
AB  - Background: Planarians are non-parasitic Platyhelminthes (flatworms) famous for
      their regeneration ability and for having a well-organized brain. Dugesia
      japonica is a typical planarian species that is widely distributed in the East
      Asia. Extensive cellular and molecular experimental methods have been developed
      to identify the functions of thousands of genes in this species, making this
      planarian a good experimental model for regeneration biology and neurobiology.
      However, no genome-level information is available for D. japonica, and few gene
      regulatory networks have been identified thus far. Results: To obtain whole
      genome information on this species and to study its gene regulatory networks, we
      extracted genomic DNA from 200 planarians derived from a laboratory-bred asexual
      clonal strain, and sequenced 476 Gb of data by second-generation sequencing. Kmer
      frequency graphing and fosmid sequence analysis indicated a complex genome that
      would be difficult to assemble using second-generation sequencing short reads. To
      address this challenge, we developed a new assembly strategy and improved the de
      novo genome assembly, producing a 1.56 Gb genome sequence (DjGenome ver1.0,
      including 202,925 scaffolds and N50 length 27,741 bp) that covers 99.4% of all
      19,543 genes in the assembled transcriptome, although the genome is fragmented as
      80% of the genome consists of repeated sequences (genomic frequency >= 2). By
      genome comparison between two planarian genera, we identified conserved non
      coding elements (CNEs), which are indicative of gene regulatory elements.
      Transgenic experiments using Xenopus laevis indicated that one of the CNEs in the
      Djndk gene may be a regulatory element, suggesting that the regulation of the ndk
      gene and the brain formation mechanism may be conserved between vertebrates and
      invertebrates. Conclusion: This draft genome and CNE analysis will contribute to
      resolving gene regulatory networks in planarians. The genome database is
      available at: http://www.planarian.jp.

PMID- 30181898
TI  - Clampdown of inflammation in aging and anticancer therapies by limiting
      upregulation and activation of GPCR, CXCR4.
AB  - One of the major pathological outcomes of DNA damage during aging or anticancer
      therapy is enhanced inflammation. However, the underlying signaling mechanism
      that drives this is not well understood. Here, we show that in response to DNA
      damage, ubiquitously expressed GPCR, CXCR4 is upregulated through the ATM kinase
      HIF1alpha dependent DNA damage response (DDR) signaling, and enhances
      inflammatory response when activated by its ligand, chemokine CXCL12. A
      pharmacologically active compound screen revealed that this increased
      inflammation is dependent on reduction in cAMP levels achieved through activation
      of Galphai through CXCR4 receptor and PDE4A. Through in vivo analysis in mice
      where DNA damage was induced by irradiation, we validated that CXCR4 is induced
      systemically after DNA damage and inhibition of its activity or its induction
      blocked inflammation as well as tissue injury. We thus report a unique DNA damage
      linked inflammatory cascade, which is mediated by expression level changes in a
      GPCR and can be targeted to counteract inflammation during anticancer therapies
      as well as aging.

PMID- 30181899
TI  - Postsynaptic p47phox regulates long-term depression in the hippocampus.
AB  - It is well documented that reactive oxygen species (ROS) affects
      neurodegeneration in the brain. Several studies also implicate ROS in the
      regulation of synapse function and learning and memory processes, although the
      precise source of ROS generation within these contexts remains to be further
      explored. Here we show that postsynaptic superoxide generation through PKCzeta
      activated NADPH oxidase 2 (NOX2) is critical for long-term depression (LTD) of
      synaptic transmission in the CA1-Shaffer collateral synapse of the rat
      hippocampus. Specifically, PKCzeta-dependent phosphorylation of p47phox at serine
      316, a NOX2 regulatory subunit, is required for LTD but is not necessary for long
      term potentiation (LTP). Our data suggest that postsynaptic p47phox
      phosphorylation at serine 316 is a key upstream determinant for LTD and synapse
      weakening.

PMID- 30181900
TI  - A growth factor-free culture system underscores the coordination between Wnt and
      BMP signaling in Lgr5+ intestinal stem cell maintenance.
AB  - Lgr5+ intestinal stem cells (ISCs) drive the fast renewal of intestinal
      epithelium. Several signaling pathways have been shown to regulate ISC fates.
      However, it is unclear what are the essential signals to sustain the ISC self
      renewal. Here we show that coordination between Wnt and BMP signaling activity is
      necessary and sufficient to maintain Lgr5+ ISCs self-renewal. The key function of
      R-spondin1 is to achieve a high activity of Wnt signaling in the organoid
      culture. Using the GSK3 inhibitor CHIR-99021 and the BMP type I receptor
      inhibitor LDN-193189, we can maintain Lgr5+ ISCs without growth factors in vitro.
      Our results define the basic signaling pathways sustaining Lgr5+ ISCs and set up
      a convenient and economical culture system for their in vitro expansion. This
      work also set up an example for growth factor-free culture of other adult stem
      cells.

PMID- 30181901
TI  - Redefining environmental exposure for disease etiology.
AB  - Etiological studies of human exposures to environmental factors typically rely on
      low-throughput methods that target only a few hundred chemicals or mixtures. In
      this Perspectives article, I outline how environmental exposure can be defined by
      the blood exposome-the totality of chemicals circulating in blood. The blood
      exposome consists of chemicals derived from both endogenous and exogenous
      sources. Endogenous chemicals are represented by the human proteome and
      metabolome, which establish homeostatic networks of functional molecules.
      Exogenous chemicals arise from diet, vitamins, drugs, pathogens, microbiota,
      pollution, and lifestyle factors, and can be measured in blood as subsets of the
      proteome, metabolome, metals, macromolecular adducts, and foreign DNA and RNA. To
      conduct 'exposome-wide association studies', blood samples should be obtained
      prospectively from subjects-preferably at critical stages of life-and then
      analyzed in incident disease cases and matched controls to find discriminating
      exposures. Results from recent metabolomic investigations of archived blood
      illustrate our ability to discover potentially causal exposures with current
      technologies.

PMID- 30181902
TI  - Prevalence and patterns of higher-order drug interactions in Escherichia coli.
AB  - Interactions and emergent processes are essential for research on complex systems
      involving many components. Most studies focus solely on pairwise interactions and
      ignore higher-order interactions among three or more components. To gain deeper
      insights into higher-order interactions and complex environments, we study
      antibiotic combinations applied to pathogenic Escherichia coli and obtain
      unprecedented amounts of detailed data (251 two-drug combinations, 1512 three
      drug combinations, 5670 four-drug combinations, and 13608 five-drug
      combinations). Directly opposite to previous assumptions and reports, we find
      higher-order interactions increase in frequency with the number of drugs in the
      bacteria's environment. Specifically, as more drugs are added, we observe an
      elevated frequency of net synergy (effect greater than expected based on
      independent individual effects) and also increased instances of emergent
      antagonism (effect less than expected based on lower-order interaction effects).
      These findings have implications for the potential efficacy of drug combinations
      and are crucial for better navigating problems associated with the combinatorial
      complexity of multi-component systems.

PMID- 30181903
TI  - Dynamic modeling of transcriptional gene regulatory network uncovers distinct
      pathways during the onset of Arabidopsis leaf senescence.
AB  - Age-dependent senescence is a multifaceted and highly coordinated developmental
      phase in the life of plants that is manifested with genetic, biochemical and
      phenotypic continuum. Thus, elucidating the dynamic network modeling and
      simulation of molecular events, in particular gene regulatory network during the
      onset of senescence is essential. Here, we constructed a computational pipeline
      that integrates senescence-related co-expression networks with transcription
      factor (TF)-promoter relationships and microRNA (miR)-target interactions.
      Network structural and functional analyses revealed important nodes within each
      module of these co-expression networks. Subsequently, we inferred significant
      dynamic transcriptional regulatory models in leaf senescence using time-course
      gene expression datasets. Dynamic simulations and predictive network perturbation
      analyses followed by experimental dataset illustrated the kinetic relationships
      among TFs and their downstream targets. In conclusion, our network science
      framework discovers cohorts of TFs and their paths with previously unrecognized
      roles in leaf senescence and provides a comprehensive landscape of dynamic
      transcriptional circuitry.

PMID- 30181904
TI  - Clinical course of acute zonal occult outer retinopathy complicated by choroidal
      neovascularization.
AB  - Purpose: To report the clinical course and multimodal imaging features of acute
      zonal occult outer retinopathy (AZOOR) complicated by choroidal
      neovascularization (CNV) treated with anti-vascular endothelial growth factor
      (VEGF) treatment or photodynamic therapy (PDT). Methods: Observational case
      series. Retrospective analysis of patients presenting to different institutions
      with evidence of AZOOR and neovascular lesions. Diagnosis of AZOOR was made on
      the basis of clinical presentation and multimodal imaging. All patients underwent
      a comprehensive ophthalmic evaluation and multimodal retinal imaging, including
      color fundus photos, fundus autofluorescence, fundus fluorescein angiography and
      spectral-domain optical coherence tomography. Results: Four patients (three
      males, mean age 53.5 years) were included in the study. Mean follow-up was 5.1
      years. Presentation of AZOOR was unilateral in two patients and bilateral in the
      remainder two patients. One of the patients presenting with unilateral AZOOR
      developed zonal lesions in the fellow eye during follow-up. All patients
      presented with unilateral type 2 (subretinal) CNV. Three patients underwent
      intravitreal anti-VEGF injections and one patient underwent a single PDT.
      Multimodal retinal imaging showed zonal or multizonal progression during
      treatment. After treatment, visual acuity and CNV stabilization was observed in
      all patients. Conclusions: The presence of CNV expands the clinical spectrum of
      AZOOR. CNV complicating AZOOR may be effectively treated with intravitreal
      injections of anti-VEGF, despite progression of the zonal lesions. Further
      studies are required to define the role of treatment in the progression of the
      zonal lesions.

PMID- 30181905
TI  - Quality dentistry and ethical dental practice.

PMID- 30181906
TI  - In vitro simulation of erosive challenges to human enamel using a novel
      artificial mouth.
AB  - This in vitro work reports upon the design, build and operation of an artificial
      environment (Saltus) that sought to simulate the process of in vivo dental
      erosion upon human enamel. A novel testing environment, housed 8 erosion testing
      substrate specimens, that on separate occasions were subject to 4 different
      experimental diets, of increasing erosive challenge, simulating the consumption
      of an acidic beverage. Each set of specimens was subjected to one of the
      experimental diets only. These were liquid only and administered the test
      beverage over a standardized range of volumes and durations. Flow of both
      artificial unstimulated and stimulated saliva was maintained throughout and the
      effects upon the substrates were measured by profilometry, surface microhardness
      determination and chemical analysis of the saliva and beverage mixture for traces
      of Calcium and Phosphate ions. The overall trend of surface hardness reduction,
      depth of surface loss and ion loss across the diets increased in proportion to
      the severity of insult. Accepting the limitations of this study Saltus appeared
      to perform well as an environment in which to simulate and assess dental erosion
      using parameters defined by previous in vivo observations of human drinking
      behaviour. The authors however acknowledge that in vitro testing can never
      replicate fully the in vivo situation.

PMID- 30181907
TI  - Effect of sodium fluoride pretreatment on the efficacy of an in-office bleaching
      agent: An in vitro study.
AB  - This in vitro study evaluated the effect of sodium fluoride (NaF) on the
      bleaching efficacy using an artificial discolored bovine tooth model. Twenty
      specimens were prepared from bovine teeth by staining with black tea extract and
      were divided into two groups (n = 10). In control group, specimens were immersed
      in distilled water for 30 min. In NaF group, specimens were applied with 0.2% NaF
      for 30 min. Then, the specimens in each group were bleached by an in-office
      bleaching material (Shofu Hi-Lite, Shofu, Kyoto, Japan). The CIE L*a*b* values
      were measured by a dental colorimeter before and after 10 consecutive bleaching
      treatments, and the color difference (DeltaE) was calculated. Brightness and
      color difference (DeltaE) increased in both groups per bleaching cycle. There
      were no statistical differences in DeltaE values between both groups (p > 0.05).
      It was concluded that the application of NaF before bleaching did not interfere
      with the bleaching effect.

PMID- 30181908
TI  - Study of factors related to the attitudes toward studying abroad among
      preclinical/clinical undergraduate dental students at three dental schools in
      Japan.
AB  - Despite of their general interests in studying abroad, there are two types of
      dental student in Japan. They are those who decide to go studying abroad and
      those who do not. The aim of this study was to clarify the factors related to the
      attitudes toward studying abroad among preclinical/clinical undergraduate dental
      students who attended three dental schools in Japan. A questionnaire was used to
      assess undergraduate dental students' attitudes toward studying abroad. We
      analyzed the differences between junior (preclinical) students and senior
      (clinical) students on concerns, and relationships between personality traits
      based on the Big Five and experiences related to studying abroad. Four hundred
      and thirty-nine undergraduate students completed the questionnaire. The senior
      dental students were more worried, more than the junior students, about "lack of
      language ability in daily life," "higher quality facilities and environment," and
      valued "dental/medical knowledges and skills" and "advantage for getting a job"
      through studying abroad. Both junior and senior students with experience of/plans
      for studying abroad reported significantly higher levels of openness to
      experience than those without such experiences or plans. The less-open group was
      more concerned with "lack of language ability in daily life/academic fields,"
      "higher quality facilities and environment," "life in a foreign country,"
      "interpersonal relationships in foreign countries," and "no friends in foreign
      countries" than the open-group. Although the preclinical and clinical dental
      students at the three dental schools in Japan had different views of concern for
      studying abroad, "openness to experience" might be a common key factor related to
      their studying abroad. However, apart from any personality factor, alleviating
      students' concerns regarding daily life adjustments might be effective in
      promoting a willingness to go studying abroad.

PMID- 30181909
TI  - Head and dental injuries or other dental problems in alpine sports.
AB  - In the hectic daily life, spending our leisure time outdoor in the mountains
      becomes more and more popular. Although information describing dental injuries in
      various sports is available, data specifically on dental trauma and other dental
      problems in alpine sports are lacking. Data of 1,128 alpinists were generated by
      using a standardized questionnaire. The questions focused on the frequency of
      head and dental injuries and other dental problems. The participating alpinists
      have been recruited through the network of alpine clubs and an outdoor equipment
      supplier. Injuries were most frequently caused by a fall while doing alpine
      sports (14.7%, = 154). Of the participants, 8.2% (n = 93) suffered from a facial
      injury: 16% (n = 15) of these had a dental trauma. Other dental problems such as
      barodontalgia were more common than dental traumas. A sensation of pressure or
      pain was noticed in 13% (n = 135) of the participants at least once. Of all the
      participants who suffered pain, 54.1% reported one or several previous
      restorations. Pain medication was beneficial in 92.1%. Dental traumas are rare
      while doing alpine sports but not negligible because of its requirement of
      lifelong therapy and incurs substantial treatment costs. An intraoral pain of a
      usually asymptomatic tissue occurred, in this sample of participants, nearly as
      often as in pilots and divers. Pain killer is an efficient tool for the alpinists
      to reduce the pain until they reach a lower altitude.

PMID- 30181910
TI  - Clinical performance of LOCATOR(r) attachments: A retrospective study with 1-8
      years of follow-up.
AB  - The use of LOCATOR(r) attachments in implant-supported removable dental
      prostheses (ISRDPs) has been evidenced with conflicting clinical behavior in
      literature. This retrospective study aimed to investigate the long-term clinical
      performance of LOCATOR(r) attachments by evaluating the frequency of the
      encountered mechanical complication events (MCEs) and the factors that play a
      role in attachment wear (AW). The study recruited participants with ISRDPs on
      LOCATOR(r) attachments. Clinical parameters, number of MCEs (attachment
      replacements, attachment loosenings, denture cap-related events, loss of
      retention and/or insert, and implant fractures), and AW were recorded.
      Nonparametric tests were applied for statistical analyses (??=0.05). Baseline
      demographics for the recruited 47 participants (mean age: 72.0 +/- 9.0 years)
      revealed an implant survival rate of 94.9% (mean observation period: 54.8
      months), average peri-implant probing depths, bleeding on probing scores, and
      plaque scores of 1.80 +/- 1.50 mm, 0.70 +/- 0.90, and 0.81 +/- 0.90,
      respectively. MCEs were directly influenced by the time in use (p < 0.001). The
      most frequently encountered MCEs were loss of retention (p < 0.001) and denture
      cap-related complications (p = 0.004). AW was found to be significantly higher in
      the maxilla than in the mandible (p = 0.028); in the maxilla, the vestibular (p =
      0.005) and mesial (p = 0.01) aspects were the most common wear sites. Maxillary
      implant overdentures revealed more vestibular AW (p = 0.013). In prostheses
      supported by >3 implants, vestibular (p = 0.046) and mesial (p = 0.032) AW were
      common. Lingual AW (p = 0.021) was observed more frequently when the support was
      <3 implants. Loss of retention and AW are the most common complications
      encountered with LOCATOR(r) attachments. Therefore, a modification in the
      attachment design along with an amelioration of the attachment surface may help
      decrease the maintenance needs and further enhance its clinical performance.

PMID- 30181911
TI  - Reliability of virtual non-contrast computed tomography angiography: comparing it
      with the real deal.
AB  - Background: Computed tomographic angiography (CTA) may require a non-contrast
      enhanced dataset for the diagnostic workup. By using dual-energy acquisition, it
      is possible to obtain a virtual non-contrast-enhanced (VNC) dataset, thereby
      possibly eliminating the non-contrast acquisition and reducing the radiation
      dose. Purpose: To compare image quality of VNC images reconstructed from arterial
      phase dual-energy CTA to true non-contrast (TNC) images, and to assess whether
      VNC images were of sufficient quality to replace TNC images. Material and
      methods: Thirty consecutive patients with suspected abdominal aortic aneurysm,
      aortic dissection, or subacute control after EVAR/TEVAR were examined with dual
      energy CT (DECT). The examination protocol included a single-energy TNC, DECT
      arterial phase (80 kV/Sn140 kV), and single-energy in venous phase of the aorta.
      A VNC dataset was obtained from the DE acquisition from arterial phase scans.
      Mean attenuation and image noise were measured within regions of interest at
      three levels in the aorta in TNC and VNC images. Comparison of the TNC and VNC
      images for artefacts was made side-by-side. Subjective evaluation included
      overall image quality on a 4-grade scale, and quantitative analysis of algorithm
      induced artefacts by two experienced readers. Results: For all cases, the aortic
      attenuation was significantly higher at VNC than at TNC. Image noise measured
      quantitatively was also significantly higher at VNC than at TNC. Subjective image
      quality was lower for VNC (mean = 3.1 for VNC, 3.7 = for TNC) but there were no
      cases rated non-diagnostic. Conclusion: VNC images based on arterial phase CTA
      have significantly higher mean attenuation and higher noise levels compared to
      TNC.

PMID- 30181912
TI  - Process improvement for reducing side discrepancies in radiology reports.
AB  - Background: Laterality errors in radiology reports can lead to serious errors in
      management. Purpose: To reduce errors related to side discrepancies in radiology
      reports from thoracic imaging by 50% over a six-month period with education and
      voice recognition software tools. Material and Methods: All radiology reports at
      the Thoracic Imaging Division from the fourth quarter of 2016 were reviewed
      manually for presence of side discrepancies (baseline data). Side discrepancies
      were defined as a lack of consistency in side labeling of any abnormality in the
      "Findings" to "Impression" sections of the reports. Process map and Ishikawa
      fishbone diagram (Microsoft Visio) were created. All thoracic radiologists were
      educated on side-related errors in radiology reports for plan-design-study-act
      cycle 1 (PDSA #1). Two weeks later, voice recognition software was configured to
      capitalize sides (RIGHT and LEFT) in the reports during dictated (PDSA# 2).
      Radiology reports were analyzed to determine side-discrepancy errors following
      each PDSA cycle (post-interventional data). Statistical run charts were created
      using QI Macros statistical software. Results: Baseline data revealed 33 side
      discrepancy errors in 47,876 reports with an average of 2.5 errors per week
      (range = 1-8 errors). Following PDSA #1, there were seven errors pertaining to
      side discrepancies over a two-week period. Errors declined following
      implementation of PDSA #2 to meet the target of 0.85 side-discrepancy error per
      week over seven weeks. Conclusion: Automated processes (such as capitalization of
      sides) help reduce left/right errors substantially without affecting reporting
      turnaround time.

PMID- 30181913
TI  - Murine gammadelta T Cells Render B Cells Refractory to Commitment of IgA Isotype
      Switching.
AB  - gammadelta T cells are abundant in the gut mucosa and play an important role in
      adaptive immunity as well as innate immunity. Although gammadelta T cells are
      supposed to be associated with the enhancement of Ab production, the status of
      gammadelta T cells, particularly in the synthesis of IgA isotype, remains
      unclear. We compared Ig expression in T cell receptor delta chain deficient
      (TCRdelta-/-) mice with wild-type mice. The amount of IgA in fecal pellets was
      substantially elevated in TCRdelta-/- mice. This was paralleled by an increase in
      surface IgA expression and total IgA production by Peyer's patches (PPs) and
      mesenteric lymph node (MLN) cells. Likewise, the TCRdelta-/- mice produced much
      higher levels of serum IgA isotype. Here, surface IgA expression and number of
      IgA secreting cells were also elevated in the culture of spleen and bone marrow
      (BM) B cells. Germ-line alpha transcript, an indicator of IgA class switch
      recombination, higher in PP and MLN B cells from TCRdelta-/- mice, while it was
      not seen in inactivated B cells. Nevertheless, the frequency of IgA+ B cells was
      much higher in the spleen from TCRdelta-/- mice. These results suggest that
      gammadelta T cells control the early phase of B cells, in order to prevent
      unnecessary IgA isotype switching. Furthermore, this regulatory role of
      gammadelta T cells had lasting effects on the long-lived IgA-producing plasma
      cells in the BM.

PMID- 30181914
TI  - Thapsigargin Increases IL-2 Production in T Cells at Nanomolar Concentrations.
AB  - Thapsigargin (TGN) is a potent and selective inhibitor of sarco-endoplasmic Ca2+
      ATPase, leading to rapid elevation of cytoplasmic Ca2+ concentration. Previous
      reports have shown that TGN increases the production of various cytokines from
      macrophages and dendritic cells. Here, we examine the effects of TGN on murine T
      cells. Nanomolar concentrations of TGN are a significant inducer of IL-2
      production with full activity at 50 nM. Micromolar concentrations of TGN,
      however, are inhibitory to IL-2 production and T cell proliferation. The IL-2
      production-inducing activity of TGN is much more prominent when T cells are
      primed with concanavalin A or anti-CD3 mAb, and is due to the increase of
      cytoplasmic Ca2+ concentration. TGN at 50 nM does not affect interferon-gamma or
      IL-4 production from T cells. Thus, the present study shows that low nanomolar
      concentrations of TGN could be useful in potentiating IL-2 production from
      antigen-primed T cells.

PMID- 30181916
TI  - Immune Network Receives First Impact Factor of 2.524.

PMID- 30181915
TI  - Damage-Associated Molecular Patterns in Inflammatory Diseases.
AB  - Damage-associated molecular patterns (DAMPs) are endogenous danger molecules that
      are released from damaged or dying cells and activate the innate immune system by
      interacting with pattern recognition receptors (PRRs). Although DAMPs contribute
      to the host's defense, they promote pathological inflammatory responses. Recent
      studies have suggested that various DAMPs, such as high-mobility group box 1
      (HMGB1), S100 proteins, and heat shock proteins (HSPs), are increased and
      considered to have a pathogenic role in inflammatory diseases. Here, we review
      current research on the role of DAMPs in inflammatory diseases, including
      rheumatoid arthritis, systemic lupus erythematosus, osteoarthritis,
      atherosclerosis, Alzheimer's disease, Parkinson's disease, and cancer. We also
      discuss the possibility of DAMPs as biomarkers and therapeutic targets for these
      diseases.

PMID- 30181917
TI  - Chemokine Network and Overall Survival in TP53 Wild-Type and Mutant Ovarian
      Cancer.
AB  - Ovarian cancer (OC) has the highest mortality rate among gynecological
      malignancies. Because chemokine network is involved in OC progression, we
      evaluated associations between chemokine expression and survival in tumor
      suppressor protein p53 (TP53) wild-type (TP53WT) and mutant (TP53m) OC datasets.
      TP53 was highly mutated in OC compared to other cancer types. Among OC subtypes,
      CXCL14 was predominantly expressed in clear cell OC, and CCL15 and CCL20 in
      mucinous OC. TP53WT endometrioid OC highly expressed CXCL14 compared to TP53m,
      showing better progression-free survival but no difference in overall survival
      (OS). TP53m serous OC highly expressed CCL8, CCL20, CXCL10 and CXCL11 compared to
      TP53WT. CXCL12 and CCL21 were associated with poor OS in TP53WT serous OC. CXCR2
      was associated with poor OS in TP53m serous OC, while CXCL9, CCL5, CXCR4, CXCL11,
      and CXCL13 were associated with better OS. Taken together, specific chemokine
      signatures may differentially influence OS in TP53WT and TP53m OC.

PMID- 30181918
TI  - T Cell-Specific Knockout of STAT3 Ameliorates Dextran Sulfate Sodium-Induced
      Colitis by Reducing the Inflammatory Response.
AB  - Signal transducer and activator of transcription 3 (STAT3) has a crucial role in
      various autoimmune disorders including, inflammatory bowel disease (IBD). Our
      previous study demonstrated that STAT3 activation by IL-6 in colonic epithelial
      cells exacerbates experimental ulcerative colitis. Activated T lymphocytes are
      also found in ulcerative colitis patients with intestinal inflammation, but the
      role of STAT3 in T cells remains elusive. To determine the STAT3 function of T
      cells in intestinal inflammation, we generated T cell-specific STAT3 knockout
      (KO) mice and used dextran sulfate sodium (DSS) to induce colitis. In this study,
      we demonstrated that T cell-specific STAT3 deletion alleviated DSS-induced
      colitis in mice, resulting in reduced histological scores and myeloperoxidase
      (MPO) activity. Importantly, the population of T cells in the spleen and lymph
      nodes was significantly decreased in the control and DSS-induced groups of STAT3
      KO mice. In addition, STAT3 deficiency in T cells markedly reduced the production
      of interferon (IFN)-gamma, IL-6, and IL-17A, whereas IL-10 secretion was
      increased. Collectively, the results suggest that STAT3 in T cells may be a
      therapeutic target in ulcerative colitis by balancing the immune response through
      T cell homeostasis.

PMID- 30181919
TI  - Optimization of Large-Scale Expansion and Cryopreservation of Human Natural
      Killer Cells for Anti-Tumor Therapy.
AB  - Allogeneic natural killer (NK) cell therapy is a potential therapeutic approach
      for a variety of solid tumors. We established an expansion method for large-scale
      production of highly purified and functionally active NK cells, as well as a
      freezing medium for the expanded NK cells. In the present study, we assessed the
      effect of cryopreservation on the expanded NK cells in regards to viability,
      phenotype, and anti-tumor activity. NK cells were enormously expanded (about
      15,000-fold expansion) with high viability and purity by stimulating CD3+ T cell
      depleted peripheral blood mononuclear cells (PBMCs) with irradiated autologous
      PBMCs in the presence of IL-2 and OKT3 for 3 weeks. Cell viability was slightly
      reduced after freezing and thawing, but cytotoxicity and cytokine secretion were
      not significantly different. In a xenograft mouse model of hepatocellular
      carcinoma cells, cryopreserved NK cells had slightly lower anti-tumor efficacy
      than freshly expanded NK cells, but this was overcome by a 2-fold increased dose
      of cryopreserved NK cells. In vivo antibody-dependent cell cytotoxicity (ADCC)
      activity of cryopreserved NK cells was also demonstrated in a SCID mouse model
      injected with Raji cells with rituximab co-administration. Therefore, we
      demonstrated that expanded/frozen NK cells maintain viability, phenotype, and
      anti-tumor activity immediately after thawing, indicating that expanded/frozen NK
      cells can provide 'ready-to-use' cell therapy for cancer patients.

PMID- 30181920
TI  - Viperin Deficiency Promotes Polarization of Macrophages and Secretion of M1 and
      M2 Cytokines.
AB  - Viperin is a multifunctional protein that was first identified in human primary
      macrophages treated with interferon-gamma and in human fibroblasts infected with
      human cytomegalovirus. This protein plays a role as an anti-viral protein and a
      regulator of cell signaling pathways or cellular metabolism when induced in a
      variety of cells such as fibroblasts, hepatocytes and immune cells including T
      cells and dendritic cells. However, the role of viperin in macrophages is
      unknown. Here, we show that viperin is basally expressed in murine bone marrow
      cells including monocytes. Its expression is maintained in bone marrow monocyte
      derived macrophages (BMDMs) depending on macrophage colony-stimulating factor (M
      CSF) treatment but not on granulocyte-macrophage colony-stimulating factor (GM
      CSF) treatment. In wild type (WT) and viperin knockout (KO) BMDMs differentiated
      with M-CSF or G-MCSF, there are little differences at the gene expression levels
      of M1 and M2 macrophage markers such as inducible nitric oxide synthase (iNOS)
      and arginase-1, and cytokines such as IL-6 and IL-10, indicating that viperin
      expression in BMDMs does not affect the basal gene expression of macrophage
      markers and cytokines. However, when BMDMs are completely polarized, the levels
      of expression of macrophage markers and secretion of cytokines in viperin KO M1
      and M2 macrophages are significantly higher than those in WT M1 and M2
      macrophages. The data suggest that viperin plays a role as a regulator in
      polarization of macrophages and secretion of M1 and M2 cytokines.

PMID- 30181922
TI  - Genome-wide profiling of sRNAs in the Verticillium dahliae-infected Arabidopsis
      roots.
AB  - Small RNAs (sRNAs, including small interfering RNAs [siRNAs] and micro RNAs
      [miRNAs]) are key mediators of RNA silencing (or RNA interference), which play
      important roles in plant development and response to biotic and abiotic
      stimulation. Verticillium wilt is a plant vascular disease caused by the soil
      borne fungal pathogens, such as Verticillium dahliae. We previously reported that
      V. dahliae infection increased two plant endogenous miRNAs that were exported to
      fungal cell to silence virulence genes. To investigate plant sRNAs in genome-wide
      response to V. dahliae infection, in this study, we constructed two sRNA
      libraries from Arabidopsis roots with and without V. dahliae infection,
      respectively. In total, 31 conserved miRNAs were found to be differentially
      expressed during the early stage of infection with V. dahliae using sRNA
      sequencing. Among these, the expression levels of miR160, miR164, miR166, miR167,
      miR390 and miR156h were confirmed by northern blot. Reverse transcription
      quantitative real time polymerase chain reaction results showed that the
      induction of miRNAs (miR160, miR164, miR166 and miR167) upon V. dahliae infection
      downregulated the expression of their targeted genes (ARF10, NAC1, PHV and ARF6),
      respectively. In addition, we identified specific phased siRNAs generated from
      distinct regions of two libraries. Profiling of these miRNAs and sRNAs lay the
      foundation for further understanding and utilising the host-induced gene
      silencing strategy to control plant vascular pathogens.

PMID- 30181921
TI  - Biomimetic delivery of signals for bone tissue engineering.
AB  - Bone tissue engineering is an exciting approach to directly repair bone defects
      or engineer bone tissue for transplantation. Biomaterials play a pivotal role in
      providing a template and extracellular environment to support regenerative cells
      and promote tissue regeneration. A variety of signaling cues have been identified
      to regulate cellular activity, tissue development, and the healing process.
      Numerous studies and trials have shown the promise of tissue engineering, but
      successful translations of bone tissue engineering research into clinical
      applications have been limited, due in part to a lack of optimal delivery systems
      for these signals. Biomedical engineers are therefore highly motivated to develop
      biomimetic drug delivery systems, which benefit from mimicking signaling molecule
      release or presentation by the native extracellular matrix during development or
      the natural healing process. Engineered biomimetic drug delivery systems aim to
      provide control over the location, timing, and release kinetics of the signal
      molecules according to the drug's physiochemical properties and specific
      biological mechanisms. This article reviews biomimetic strategies in signaling
      delivery for bone tissue engineering, with a focus on delivery systems rather
      than specific molecules. Both fundamental considerations and specific design
      strategies are discussed with examples of recent research progress, demonstrating
      the significance and potential of biomimetic delivery systems for bone tissue
      engineering.

PMID- 30181923
TI  - Do volatile compounds produced by Fusarium oxysporum and Verticillium dahliae
      affect stress tolerance in plants?
AB  - Volatile compounds (VCs) produced by diverse microbes seem to affect plant
      growth, development and/or stress tolerance. We investigated how VCs released by
      soilborne fungi Fusarium oxysporum and Verticillium dahliae affect Arabidopsis
      thaliana responses to abiotic and biotic stresses. Under salt stress, VCs from
      both fungi helped its growth and increased chlorophyll content. However, in
      contrast to wild-type A. thaliana (Col-0), V. dahliae VCs failed to increase leaf
      surface area in auxin signalling mutants aux1-7, tir1-1 and axr1-3. Compared to
      wild-type Col-0, the degree of lateral root density enhanced by V. dahliae VCs in
      these mutants was also reduced. Consistent with the involvement of auxin
      signalling in fungal VC-mediated salt torelance, A. thaliana line carrying
      DR5::GUS displayed increased auxin accumulation in root apex upon exposure to V.
      dahliae VCs, and 1-naphthylphthalamic acid, an auxin transport inhibitor,
      adversely affected V. dahliae VC-mediated salt tolerance. F. oxysporum VCs
      induced the expression of PR1 but not PDF1.2 in A. thaliana lines containing
      PR1::GUS and PFD1.2::GUS. When challenged with Pseudomonas syringae after the
      exposure to F. oxysporum VCs, A. thaliana showed reduced disease symptoms.
      However, the number of bacterial cells in F. oxysporum VC-treated plants was not
      significantly different from that in control plants.

PMID- 30181924
TI  - Introgression and gene family contraction drive the evolution of lifestyle and
      host shifts of hypocrealean fungi.
AB  - Hypocrealean fungi (Ascomycota) are known for their diversity of lifestyles.
      Their vital influences on agricultural and natural ecosystems have resulted in a
      number of sequenced genomes, which provide essential data for genomic analysis.
      Totally, 45 hypocrealean fungal genomes constructed a phylogeny. The phylogeny
      showed that plant pathogens in Nectriaceae diverged earliest, followed by animal
      pathogens in Cordycipitaceae, Ophiocordycipitaceae and Clavicipitaceae with
      mycoparasites in Hypocreaceae. Insect/nematode pathogens and grass endophytes in
      Clavicipitaceae diverged at last. Gene families associated with host-derived
      nutrients are significantly contracted in diverged lineages compared with the
      ancestral species. Introgression was detected in certain lineages of hypocrealean
      fungi, and the main functions of the genes located in the introgressed regions
      are involved in host recognition, transcriptional regulation, stress response and
      cell growth regulation. These results indicate that contraction of gene families
      and introgression might be main mechanisms to drive lifestyle differentiation and
      evolution and host shift of hypocrealean fungi.

PMID- 30181925
TI  - Chitin and chitin-related compounds in plant-fungal interactions.
AB  - Chitin is the second abundant polysaccharide in the world after cellulose. It is
      a vital structural component of the fungal cell wall but not for plants. In
      plants, fungi are recognised through the perception of conserved microbe
      associated molecular patterns (MAMPs) to induce MAMP-triggered immunity (MTI).
      Chitin polymers and their modified form, chitosan, induce host defence responses
      in both monocotyledons and dicotyledons. The plants' response to chitin,
      chitosan, and derived oligosaccharides depends on the acetylation degree of these
      compounds which indicates possible biocontrol regulation of plant immune system.
      There has also been a considerable amount of recent research aimed at elucidating
      the roles of chitin hydrolases in fungi and plants as chitinase production in
      plants is not considered solely as an antifungal resistance mechanism. We discuss
      the importance of chitin forms and chitinases in the plant-fungal interactions
      and their role in persistent and possible biocontrol. Abbreviations ET, ethylene;
      GAP, GTPase-activating protein; GEF, GDP/GTP exchange factor; JA, jasmonic acid;
      LysM, lysin motif; MAMP, microbe-associated molecular pattern; MTI, MAMP
      triggered immunity; NBS, nucleotide-binding site; NBS-LRR, nucleotide-binding
      site leucine-rich repeats; PM, powdery mildew; PR, pathogenesis-related; RBOH,
      respiratory burst oxidase homolog; RLK, receptor-like kinase; RLP, receptor-like
      protein; SA, salicylic acid; TF, transcription factor.

PMID- 30181926
TI  - A nuclear contortionist: the mitotic migration of Magnaporthe oryzae nuclei
      during plant infection.
AB  - Magnaporthe oryzae is a filamentous fungus, which causes significant destruction
      to cereal crops worldwide. To infect plant cells, the fungus develops specialised
      constricted structures such as the penetration peg and the invasive hyphal peg.
      Live-cell imaging of M. oryzae during plant infection reveals that nuclear
      migration occurs during intermediate mitosis, in which the nuclear envelope
      neither completely disassembles nor remains entirely intact. Remarkably, in M.
      oryzae, mitotic nuclei show incredible malleability while undergoing confined
      migration through the constricted penetration and invasive hyphal pegs. Here, we
      review early events in plant infection, discuss intermediate mitosis, and
      summarise current knowledge of intermediate mitotic nuclear migration in M.
      oryzae.

PMID- 30181928
TI  - Arbuscular mycorrhiza fungi increased the susceptibility of Astragalus adsurgens
      to powdery mildew caused by Erysiphe pisi.
AB  - Powdery mildew caused by Erysiphe pisi is a major factor that affects the growth
      of standing milkvetch (Astragalus adsurgens). As arbuscular mycorrhizal fungi
      (AMF) have shown to be enhancing the resistance of plants to biotrophic pathogens
      such as powdery mildew, a study was carried out to look at the effects of three
      AMF, either singularly or in combination, on the growth of standing milkvetch and
      susceptibility to E. pisi. The results showed that the presence of AMF enhanced
      the growth of standing milkvetch even though their presence in the roots
      increased susceptibility to this foliage pathogen compared with plants having no
      AMF. This increase in growth of plants with severe infection of powdery mildew
      was especially surprising as leaves contained lower levels of chlorophyll than
      plants without AMF and had a greater concentration of malondialdehyde, an
      indicator of the damage of cell membrane. The effects on the extent of growth and
      powdery mildew enhancement differed inconsistently with the type of AMF in roots.
      The effects on growth and powdery mildew were not related to intensity of AMF
      colonisation. The peroxidase (POD) was consistently higher activity (15% to 72%)
      in plants with AMF than plants without them.

PMID- 30181927
TI  - Regulatory network of genes associated with stimuli sensing, signal transduction
      and physiological transformation of appressorium in Magnaporthe oryzae.
AB  - Rice blast caused by Magnaporthe oryzae is the most destructive disease affecting
      the rice production (Oryza sativa), with an average global loss of 10-30% per
      annum. Recent reports have indicated that the fungus also inflicts blast disease
      on wheat (Triticum aestivum) posing a serious threat to the wheat production. Due
      to its easily detected infectious process and manoeuvrable genetic manipulation,
      M. oryzae is considered a model organism for exploring the molecular mechanism
      underlying fungal pathogenicity during the pathogen-host interaction. M. oryzae
      utilises an infectious structure called appressorium to breach the host surface
      by generating high turgor pressure. The appressorium development is induced by
      physical and chemical cues which are coordinated by the highly conserved
      cAMP/PKA, MAPK and calcium signalling cascades. Genes involved in the
      appressorium development have been identified and well studied in M. oryzae, a
      summary of the working gene network linking stimuli sensing and physiological
      transformation of appressorium is needed. This review provides a comprehensive
      discussion regarding the regulatory networks underlying appressorium development
      with particular emphasis on sensing of appressorium inducing stimuli, signal
      transduction, transcriptional regulation and the corresponding developmental and
      physiological responses. We also discussed the crosstalk and interaction of
      various pathways during the appressorium development.

PMID- 30181929
TI  - Phytohormones: the chemical language in Magnaporthe oryzae-rice pathosystem.
AB  - Phytohormones (also named as plant hormones) are chemicals produced by plants in
      order to modulate various aspects of plant development, stress responses and
      defence. Recent studies revealed that fungi can also produce phytohormones or
      phytohormone-mimiking molecules, while it remains poorly understood about the
      details in the role and regulatory mechanism of such fungal produced
      phytohormonal molecules in plant-fungus interactions. The rice-blast fungus
      Magnaporthe oryzae imposes a great threat to global food security. Intensive
      investigation has been conducted to elucidate M. oryzae pathogenicity and rice
      (Oryza sativa L.) defense mechanism against blast disease, in order to provide
      theoretical basis and/or identify potential target(s) for developing novel
      disease control strategies, as well as for breeding of resistance varieties.
      Phytohormones have been demonstrated to play conserved and divergent roles in
      fine-tuning the balance of rice growth and immunity towards M. oryzae. Meanwhile,
      M. oryzae evolved elaborate strategy to manipulate the rice phytohormones
      metabolism, or even directly produce and secrete phytohormones, during their
      invasion process. In this review, we discuss the chemical communication in term
      of phytohormones in M. oryzae-rice pathosystem.

PMID- 30181930
TI  - Metastatic squamous cell carcinoma of the skin with clinical response to
      lapatinib.
AB  - Background: Lapatinib is a tyrosine kinase inhibitor that blocks the HER2
      receptor and is typically used in the setting of metastatic breast cancer. Both
      ERBB2 (HER2) and ERBB3 (HER3) belong to the same family of receptor tyrosine
      kinases. Dimerization of these receptors leads to activation of cell
      proliferation and survival pathways, granting oncogenic potential to dysregulated
      ERBB/HER receptors. Next generation sequencing (NGS) of tumors has ushered in a
      new era of personalized oncology therapy and has the ability to detect mutations
      in ERBB receptors. Case presentation: We present a patient with metastatic
      cutaneous squamous cell carcinoma who failed surgery, radiation, and anti-PD1
      therapy, but showed clinical response to a drug targeting an ERBB3 mutation
      identified with NGS. Following initiation of the drug lapatinib, this patient
      exhibited dramatic tumor regression in the skin, soft tissue, bone and nerves.
      Conclusions: Cutaneous squamous cell carcinoma is the 2nd most common skin cancer
      in humans and future investigation of ERBB2 targeted therapies may provide an
      effective treatment strategy for patients with mutations in the ERBB2/3 pathway.

PMID- 30181931
TI  - A Case of Concomitant Emphysematous Cystitis and Clostridium difficile Colitis
      with Pneumoperitoneum.
AB  - Emphysematous cystitis (EC) is a rare condition described as air within the wall
      and lumen of the urinary bladder. It is a complicated form of urinary tract
      infection caused by gas-forming bacteria. Pneumoperitoneum described as gas in
      the peritoneum is usually seen with abdominal hollow organ perforation, and
      approximately 10% of cases have been reported that are not associated with
      abdominal hollow viscus perforation. To the best of our knowledge, no case of EC
      with pneumoperitoneum in the setting of concurrent Klebsiella urinary tract
      infection and Clostridiumdifficile (C. difficile) colitis have been reported.
      Here we present a unique case of EC with pneumoperitoneum, in a patient with
      recurrent C. difficile infection and Klebsiella pneumonia-urinary tract
      infection, treated conservatively with a favorable outcome.

PMID- 30181932
TI  - A Patient with Artifactually Low Serum High Density Lipoprotein Cholesterol Due
      to Waldenstrom Macroglobulinemia.
AB  - When very low or undetectable high density lipoprotein (HDL)-cholesterol (HDL-C)
      is encountered in clinical practice, a paraproteinemia should be suspected in the
      absence of genetic or more obvious secondary causes. We reported a case of
      artifactually low HDL-C in a 68-year-old man with a past medical history of
      vitamin B12 deficiency. Lipid panel showed total cholesterol (TC) 144 mg/dl,
      triglycerides (TG) 79 mg/dl, HDL-C 5 mg/dl, and low density lipoprotein (LDL) 123
      mg/dl. HDL-C, which was determined three years prior to this presentation was
      found normal. The patient was prescribed extended release nicotinic acid. Further
      workup performed showed the ratio of APO B/APO A1 0.36 and direct LDL 28 mg/dl.
      In the absence of genetic or more obvious secondary causes, we hypothesized that
      low HDL-C in this patient was due to paraprotein interference in vitro with the
      liquid homogenous HDL assay. Serum protein electrophoresis demonstrated normal
      IgG and IgA and an abnormally high IgM at 3510 mg/dl (57-266). A bone marrow
      biopsy revealed Waldenstrom macroglobulinemia. A diagnostic workup for an
      isolated low HDL-C unmasking the diagnosis of Waldenstrom macroglobulinemia has
      been rarely reported. Care must be taken when using the homogeneous method for
      direct measurement of HDL-C as artifactually undetectable HDL-C might result in
      the mismanagement of patients with paraproteinemia.

PMID- 30181933
TI  - The impact of the intestinal microbiome on bone health.
AB  - Intestinal microbial flora, known as the second gene pool of the human body, play
      an important role in immune function, nutrient uptake, and various activities of
      host cells, as well as in human disease. Intestinal microorganisms are involved
      in a variety of mechanisms that affect bone health. Gut microbes are closely
      related to genetic variation, and gene regulation plays an important part in the
      development of bone-related diseases such as osteoporosis. Intestinal
      microorganisms can disrupt the balance between bone formation and resorption by
      indirectly stimulating or inhibiting osteoblasts and osteoclasts. In addition,
      intestinal microorganisms affect bone metabolism by regulating growth factors or
      altering bone immune status and can also alter the metabolism of serotonin,
      cortisol, and sex hormones, thereby affecting bone mass in mice. Moreover,
      probiotics, antibiotics, and diet can change the composition of the intestinal
      microbial flora, thus affecting bone health and also potentially helping to treat
      bone disease. Studying the relationship between intestinal flora and osteoblasts,
      osteoclasts, and bone marrow mesenchymal stem cells may provide a basis for
      preventing and treating bone diseases. This paper reviews recent advances in the
      study of the relationship between intestinal microflora and bone disease.

PMID- 30181934
TI  - National information system for rare diseases with an approach to data
      architecture: A systematic review.
AB  - The study aims to systematically review literature on the rare diseases
      information system to identify architecture of this system from a data
      perspective. The search for relevant English language articles, based on keywords
      in title, abstract, Mesh and Emtree terms, was done in Pubmed and Embase (from
      1980 to June 2017), Scopus, Science Direct and Cochran (from 1980 to July 2017).
      Articles were selected if they addressed data architecture of information systems
      with a focus on rare disease, and if at least one of their objectives dealt with
      design, implementation, and development of rare diseases information systems.
      Thirty-five studies met the inclusion criteria. The findings were categorized
      into six groups. This first group addressed organizations acting as data
      generators, data users, and data governors. The second group was related to data
      sources and databases. Datasets and data elements formed the third group of
      findings, including common datasets, specific datasets, and complementary
      datasets. The fourth group of findings was in relation to data standards. Data
      sharing and interactions among relevant bodies included the fifth group of the
      findings. The last group of findings was pertinent to procedures and criteria
      used for checking the quality of data, as cross review checking was a main
      procedure assessing the accuracy, consistency, and completeness of data. Design
      and development of an integrated information system for rare diseases considering
      data architecture principles in practice could help eliminating issues with
      management of rare diseases through facilitating sharing information and
      experiences.

PMID- 30181935
TI  - Assessment of the impact of an exercise program on the physical and functional
      capacity in patients with autosomal recessive spastic ataxia of Charlevoix
      Saguenay: An exploratory study.
AB  - Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a
      neuromuscular disorder caused by the mutation of the SACS gene. Clinical symptoms
      of this disease include progressive ataxia, spasticity, and peripheral
      neuropathy. Similar to other neuromuscular disorders, these patients are prone to
      physical deconditioning which may lead to a loss of functional capacity. This
      paper aims to evaluate the impact of a training program on the physical fitness
      and the functional capacity of ARSACS patients. Twelve patients (age: 28.1 +/-
      8.2 years) participated in this study. They followed an eight-week training
      program including physical activities, strength-power and aerobic training.
      Compared to the initial evaluation, measures of physical fitness and functional
      capacity were significantly improved (p <= 0.05) for 11 of the 12 tests. Positive
      gains were also observed for fall frequency and for upper-limb incoordination.
      This paper supports the importance of a training program for ARSACS patients in
      order to improve their quality of life. Through these types of interventions, it
      may be possible to slow down the progression of the disease and help maintain
      functional capacity.

PMID- 30181936
TI  - Multidrug resistant Elizabethkingia meningoseptica bacteremia - Experience from a
      level 1 trauma centre in India.
AB  - Elizabethkingia meningoseptica (E. meningoseptica) is a non-fermenting gram
      negative organism that is commonly detected in the soil and water but is rarely
      reported to cause human infection. However it is emerging as a nosocomial
      pathogen in patients admitted in intensive care units (ICUs). Infections caused
      by this organism have a high mortality rate due to lack of effective therapeutic
      regimens and its intrinsic resistance to multiple antibiotics. We report our
      experience in managing Elizabethkingia meningoseptica (E. meningoseptica)
      septicemia in our ICU patients with septic shock during prolonged intensive care
      management. Over a two year period four cases were admitted into the polytrauma
      ICU developed sepsis due to E. meningoseptica. All these patients were on
      mechanical ventilation, had central venous catheter (CVC) and were exposed to
      various broad spectrum antibiotics. Of the four patients, three died and one
      recovered. E. meningoseptica infection should be considered as a possible
      etiological agent of sepsis in patients who do not respond to empirical therapy,
      as this results in an inappropriate choice of antimicrobial therapy, leading to
      increased morbidity and mortality of patients. Its unusual resistance pattern
      along with inherent resistance to colistin makes this organism difficult to treat
      unless susceptibility patterns are available.

PMID- 30181937
TI  - Underlying etiology determines the outcome in atraumatic chylous ascites.
AB  - Chylous ascites is an uncommon entity and infectious etiology is the most common
      cause in developing countries. However, recently, whether there is any change in
      trend of etiologies in developing countries is not known. In this study, a
      retrospective analysis of the data of cases of atraumatic chylous ascites was
      conducted. Twelve patients of atraumatic chylous ascites with a mean age of 35
      years were studied and 6 of them were males. The mean duration of symptoms was
      9.6 months and the clinical presentation was abdominal distension (12 cases),
      pain abdomen (10 cases), loss of appetite and weight (9 cases), peripheral
      lymphadenopathy (4 cases) and fever (3 cases). Etiologies were tuberculosis (3
      cases), malignancy (2 cases), radiotherapy related (2 cases), pancreatitis
      related (2 cases), lymphatic malformation (2 cases) and multifactorial (1 case).
      Eight improved with conservative measures, 2 were lost to follow up and 2 died.
      Our outcomes found infectious etiology still as the most common cause of
      atraumatic chylous ascites. Benign treatable causes could be managed successfully
      with conservative measures while malignant etiology had a poor prognosis.
      Underlying etiology determines the outcome in atraumatic chylous ascites.

PMID- 30181938
TI  - Is it always cancer? A curious case of benign intracranial hypertension in
      chronic myeloid leukemia.
AB  - 28-year-old African American female with chronic myeloid leukemia (CML) presented
      with blurry vision for 4-5 days prior to presentation associated with right-sided
      headaches. Patient was on treatment for the CML but never had hematological
      remission. Patient saw an ophthalmologist who told her that she has bilateral
      optic disc swelling and advised her to get an MRI of the brain. She came to the
      ER due to worsening headache and blurry vision. The funduscopic examination
      showed significant bilateral papilledema. Laboratory evaluation revealed a
      leukocytosis of 240 * 103/uL with platelet count of 1,202 * 103. The white cell
      differential count showed 17% blasts along with myelocytes and meta-myelocytes.
      MRI of brain revealed non-specific CSF flair signal. Lumbar puncture (LP) showed
      significantly elevated opening pressures. The CSF composition was however normal.
      The patient felt much relief of her symptoms following the LP. The papilledema
      was thought to be due to benign intracranial hypertension (ICH), which was
      attributed to poor CSF absorption due to resistance to flow of CSF caused by the
      high WBC count. She received 2 cycles of leukopheresis which dropped her WBC
      count. She was also started on acetazolamide for the benign ICH and her symptoms
      improved considerably. Patients with CML can thus present with symptoms mimicking
      CNS involvement of the disease such as headaches and blurry vision, but that
      could be attributed to the poor CSF resorption given the leukocytosis rather than
      spread of the disease itself.

PMID- 30181939
TI  - Traumatic neuroma as a rare cause of intractable neuropathic breast pain
      following cancer surgery: Management and review of the literature.
AB  - Traumatic neuroma of the breast after cancer surgery is a very rare clinical
      entity with only a few cases having been reported to date. We herein present a
      very rare case of traumatic breast neuroma in a postmenopausal patient with a
      history of breast-conserving surgery, who presented with a four-month history of
      intractable neuropathic breast pain. Diagnostic evaluation and management are
      discussed along with a review of the literature. Traumatic breast neuromas are
      very rare benign lesions that have been reported mainly after mastectomy. Our
      literature review yielded only 35 cases of traumatic breast neuromas in 28
      patients, reported so far. Although imaging features may be indicative of a
      benign lesion, surgical excision is necessary to obtain a definitive diagnosis
      and to rule out a recurrent breast cancer. Conservative treatment is feasible in
      properly selected cases with asymptomatic neuromas after an accurate tissue
      sampling. The case presented herein underlines the necessity to consider
      traumatic neuroma in the differential diagnosis in patients with a history of
      breast surgery presenting with refractory neuropathic breast pain. A high index
      of suspicion is required because the lesion may be too small and can be missed on
      imaging investigations.

PMID- 30181940
TI  - Co-occurrence of Gomez-Lopez-Hernandez syndrome and Autism Spectrum Disorder:
      Case report with review of literature.
AB  - We report on Gomez-Lopez-Hernandez syndrome (GLHS) in a Caucasian patient,
      Georgian, 36 months, male, only child born to non-consanguineous parents. There
      were no similar cases in the family and among close relatives. MRI study
      confirmed rhombencephalosynapsis (fusion of cerebellar hemispheres in combination
      with the agenesis of cerebellar vermis) and mild dilation of the lateral
      ventricles. Other main findings are bilateral parieto-temporal alopecia and
      brachiturricephaly (broad skull shape and tower-like elongation of the cranium in
      the vertical axis), low-set posteriorly retracted ears, strabismus (in the right
      eye), hypotonia (Beighton scale score - 6) and ataxia (trouble maintaining
      balance). Patient has no signs of trigeminal anesthesia, no recurrent, painless
      eye infections, corneal opacities and ulcerated wounds on the facial skin and
      buccal mucosa were observed. Based on the scientific literature we suggest a
      finding of brachiturricephaly in addition to rhombencephalosynapsis and bilateral
      alopecia sufficient to put a diagnosis of GLHS. Patient did not speak,
      disregarded guardians and clinician addressing him, did not make eye contact, was
      restless and occasionally displayed aggression and self-injurious behavior. These
      symptoms confirm the earlier diagnosis of Autism Spectrum Disorder (ASD).
      Therefore, the current study describes a case of co-occurrence of GLHS and ASD.

PMID- 30181941
TI  - Esophageal arteriovenous malformation, a rare cause of significant upper
      gastrointestinal bleeding: Case report and review of literature.
AB  - Gastrointestinal (GI) arteriovenous malformations (AVMs) are a well-known source
      of bleeding with colon being the most common site, but they can also occur in
      rare locations like the esophagus which may present with life threatening
      bleeding. We report the case of a 51-year-old male with end stage renal disease
      (ESRD) presenting with hematemesis and acute on chronic anemia. Further
      investigation showed an esophageal AVM which is an unusual location and it was
      successfully treated with an endoscopic clip instead of argon plasma coagulation
      (APC) due to its challenging location and esophageal wall motion from breathing.
      The patient continued to be asymptomatic without any upper and lower GI bleeding
      during his 20 months follow up period after the endoscopic management. Review of
      literature showed only 10 cases of AVMs involving esophagus and the average age
      of presentation was 52 years with a male predominance. We also provide an
      overview of those cases in the discussion section below.

PMID- 30181942
TI  - Recurrent chylous effusions and venous thrombosis: Uncommon presentation of a
      common condition.
AB  - Spontaneous bilateral chylothorax and chylous ascites rarely develop in
      conjunction with systemic venous thrombosis, and the most common cause of non
      traumatic chylous effusion is a malignancy. A 23-year-old immunocompetent female
      presented with a fever of 5 months' duration associated with progressive
      shortness of breath and abdominal distension. Evaluation revealed bilateral
      chylothorax, chylous ascites, and multiple venous thrombosis. Anti-tubercular
      drugs were initiated on the basis of a lymph node biopsy and computed tomography
      findings, but her symptoms worsened, and she developed massive bilateral pleural
      effusions with type 2 respiratory failure requiring invasive mechanical
      ventilation. She was managed with anti-tubercular drugs, chest tube drainage,
      octreotide, anticoagulants, and other supportive treatments. A multipronged
      approach to the management of chylous effusions and addition of octreotide led to
      resolution of symptoms. The challenges faced in diagnosing and managing this case
      are discussed in this report.

PMID- 30181943
TI  - Successful treatment of acute-on-chronic liver failure and hemolytic anemia with
      hepato-protective drugs in combination with intravenous ozone without steroids: A
      case report.
AB  - Both acute-on-chronic liver failure (ACLF) and autoimmune hemolytic anemia (AIHA)
      are common causes of jaundice. A co-occurrence of ACLF and AIHA is rare in
      clinical practice. This report describes a male elderly patient who developed
      persistently increased levels of total bilirubin and ascites after endoscopic
      retrograde cholangiopancreatography for the successful treatment of common bile
      duct stones. Eventually, he was diagnosed with ACLF and AIHA according to current
      diagnostic criteria. The patient was given conventional hepato-protective drugs,
      human albumin, and diuretics in combination with immune ozone without steroids,
      and he responded well. The therapeutic role of immune ozone in this case is also
      discussed. When immune ozone was given, total bilirubin gradually decreased;
      however, no change in total bilirubin was observed after immune ozone was
      stopped. Notably, when immune ozone was re-initiated, total bilirubin decreased
      again.

PMID- 30181944
TI  - A catastrophic nightmare of the interventional cardiologist: Iatrogenic left main
      artery dissection and longitudinal stent deformation.
AB  - Iatrogenic left main coronary artery dissection is a rare but potentially life
      threatening complication of invasive coronary procedures. The newer generation
      drug eluting stents have shown a greater safety and efficacy compared to first
      generation drug eluting stents. We report a 60-year-old woman with iatrogenic
      left main coronary artery dissection who failed bailout stenting and underwent
      coronary artery bypass grafting. The strategy for managing left main coronary
      artery dissection is variable and depends upon the mechanism, the comorbidities
      of the patient and degree of hemodynamic stability. Longitudinal stent
      deformation is a rarely encountered complication but can be seen in complex
      lesions such as ostial, bifurcation and left main coronary artery lesions. The
      interventionists must be aware of this complication.

PMID- 30181945
TI  - The Reduction of Dissolved Oxygen During Magnesium Corrosion.
AB  - The consumption of dissolved oxygen (DO) during the corrosion of commercially
      pure magnesium specimens was investigated by localized corrosion techniques. The
      concentration of oxygen and the local current density on the near-surface of
      magnesium were measured simultaneously by a micro-optode DO sensor and the
      scanning vibrating electrode technique (SVET), respectively. Diamond
      microelectrodes were also used for DO mapping. Significant DO depletion was found
      since the initial immersion time of Mg in NaCl 0.5 m, and a correlation could be
      established between DO consumption and areas of anodic and cathodic activity.
      These findings assume particular relevance for the corrosion of Mg alloys or
      magnesium components with impurity levels higher than the tolerance limit.
      Moreover, this study points out the significance of the partial oxygen pressure
      as an influential parameter during magnesium corrosion.

PMID- 30181946
TI  - Sleep matters: The association of race, bedtime, outdoor time, and physical
      activity with preschoolers' sleep.
AB  - Sleep is necessary for optimal functioning. Little is known about the extent to
      which race and opportunities to be active influence sleep in preschool-aged
      children attending full-day child care. Participants (n = 359) in this cross
      sectional study attended 30 randomly selected, childcare centers in Cincinnati,
      OH. Data collection occurred from November 2009 to January 2011. Hierarchical
      linear regression and generalized estimating equations tested for associations
      between nighttime sleep duration and race, outdoor/indoor active time, actual
      physical activity (PA), screen time, daytime nap, and bedtime after 9 pm.
      Participants slept a mean +/- SD of 1.5 +/- 0.8 h at childcare and 9.7 +/- 1.0 h
      at bedtime. White children (beta = 0.57 +/- 0.14, p < 0.01) and children
      identifying as Other race (beta = 0.40 +/- 0.15, p < 0.01) slept more hours than
      Black children at nighttime. White children were less likely to nap at childcare
      than Black children. Inside PA time provided was associated with increased
      nighttime sleep duration (beta = 0.092 +/- 0.04 h per 30 min PA, p < 0.03). There
      was no association between outdoor time or moderate to vigorous PA and nighttime
      sleep. Black children slept less at night on average, but were more likely to
      engage in nap sleep at childcare resulting in similar overall sleep duration.
      Additional studies in diverse populations that explore the effects of nighttime
      versus nap time sleep on child health and well-being are needed.

PMID- 30181947
TI  - CDC childhood physical activity strategies fail to show sustained fitness impact
      in middle school children.
AB  - An increasing number of children are now obese and fail to meet minimum
      recommendations for physical activity (PA). Schools play a critical role in
      impacting children's activity behaviors, including PA. Our objective was to
      assess whether CDC-based school-centered strategies to promote PA increase long
      term cardiovascular fitness (CVF) levels in students in schools. A prospective
      observational trial was conducted in 26 middle schools to implement CDC school
      based strategies to increase PA for 3 years. Students had CVF assessed by
      Fitnessgram (PACER), a 20-meter shuttle run, at the start and end of each school
      year. A post-study questionnaire was administered to assess each school's
      strategy adherence. At baseline, 2402 students with a mean age 12.2 +/- 1.1 years
      showed a mean CVF measured by PACER of 33.2 +/- 19.0 laps (estimated VO2max 44.3
      +/- 5.3 ml/kg/min). During the first year, there was a significant increase in
      the mean PACER score (Delta = 3, 95% CI: 2-4.1 laps, p < 0.001) and PACER z-score
      (Delta = 0.09, 95% CI: 0.04-0.14, p = 0.001). Subsequently, however, a
      significant negative trend in PACER z-scores occurred (beta = -0.02, p < 0.0001)
      so that over the 3-year study period, the intervention did not increase overall
      CVF. This effort to implement CDC school-based PA strategies in middle schools
      did not result in sustained increase in CVF over 3 years. It remains to be
      clarified whether this limited efficacy indicates that CDC physical activity
      strategies are not sufficiently robust to meaningfully impact health outcomes
      and/or additional support is needed in schools to improve fidelity of
      implementation.

PMID- 30181948
TI  - Rasmussen's pseudoaneurysm- case report.
AB  - Background: Pulmonary aneurysms and pseudoaneurysms have various etiologies;
      however, the term Rasmussen's pseudoaneurysm refers specifically to a focal
      dilatation of a branch of the pulmonary artery into adjacent tuberculous cavity.
      The incidence of such tuberculosis related pulmonary vascular complication is
      extremely rare, hence, under recognized by many physicians. Management of
      pulmonary pseudoaneurysms is challenging as they present by life-threatening
      hemoptysis. Furthermore, contrary to the most causes of massive hemoptysis their
      bleeding is of pulmonary rather than bronchial artery origin. Prompt diagnosis
      and early interventions are needed as a very high mortality rate is associated
      with this illness. Case description: We are reporting on a case of a young male
      who was presented to our hospital with recurrent episodes of massive hemoptysis
      and was diagnosed to have pulmonary tuberculosis. Despite being actively treated,
      his hemoptysis persisted. We describe in this case the role of different
      diagnostic modalities and the available therapeutic options. Conclusion:
      Rasmussen's psudoaneurysm is rare and potentially lethal pulmonary vascular
      complication of tuberculosis. It should be considered in the differential
      diagnosis of hemoptysis in patients known or suspected to have pulmonary
      tuberculosis. In such cases, multidetector computed tomography (MDCT) scanning is
      the investigation of choice to confirm the diagnosis and to localize the source
      of bleeding prior to the therapeutic interventions. Head to head comparison
      between interventional radiology procedures and surgery in treatment of pulmonary
      psudoaneurysms is lacking, thus, choice depend on the availability and local
      expertise.

PMID- 30181949
TI  - Actinomyces viscosus causing disseminated disease in a patient on methotrexate.
AB  - Actinomycosis is an uncommon infectious disease caused predominantly by
      Actinomyces israelii. Actinomycosis usually involves the cervicofacial, thoracic,
      abdominal, and pelvic region, dissemination is uncommon. Actinomyces viscosus are
      commensal organisms that make up the normal flora of the oropharynx of humans and
      has rarely been reported to cause disease. Here, we report a unique case of
      disseminated actinomycosis with lung and brain lesions caused by Actinomyces
      viscosus resembling lung cancer with metastasis in a 74 year old male. Cultures
      from skin lesions confirmed A. viscosus. Although the patient was
      immunocompromised, antibiotic treatment with a penicillin-based regimen was
      effective.

PMID- 30181950
TI  - Successful long-term treatment of persistent pulmonary air leak in pneumocystis
      jirovecii pneumonia by unidirectional endobronchial valves.
AB  - Spontaneous pneumothorax is a rare complication of pneumocystis jirovecii
      pneumonia. We report a patient with pneumocystis jirovecii pneumonia and therapy
      refractory, right-sided pneumothorax due to persistent air leak (PAL) despite
      prolonged chest tube placement and multiple pleurodesis attempts. Due to the
      patient's morbidity, we evaluated if the PAL can be sealed by unidirectional
      endobronchial valves (EBVs). After occlusion of the right upper lobe by a balloon
      catheter, the air leak flow-rate decreased from 800 ml/min to 250 ml/min. Zephyr
      EBVs (ZEBVs) were placed in the segmental right upper lobe bronchi and
      subsequently, a complete resolution of the pneumothorax was noted. During 30
      months of follow-up, neither recurrence of pneumothorax nor any adverse events of
      EBV treatment were noted. We conclude that ZEBV placement might be an effective
      and well-tolerated treatment option for PAL secondary to pneumocystis jirovecii
      pneumonia with promising long-term results.

PMID- 30181951
TI  - Improvement in anti-N-methyl-d-aspartate receptor antibody-mediated temporal lobe
      epilepsy with amygdala enlargement without immunotherapy.
AB  - Focal neuroinflammation is considered one of the hypotheses for the cause of
      temporal lobe epilepsy (TLE) with amygdala enlargement (AE). Here, we report a
      case involving an adult female patient with TLE-AE characterized by late-onset
      seizures and cognitive impairment. Anti-N-methyl-d-aspartate receptor (NMDAR)
      antibodies were detected in her cerebrospinal fluid. However, administration of
      appropriate anti-seizure drugs (ASD), without immunotherapy, improved TLE-AE
      associated with NMDAR antibodies. In the present case, two clinically significant
      observations were made: 1) anti-NMDAR antibody-mediated autoimmune processes may
      be associated with TLE-AE, and 2) appropriate administration of ASD alone can
      improve clinical symptoms in mild cases of autoimmune epilepsy.

PMID- 30181952
TI  - Auras localized to the temporal lobe disrupt verbal memory and learning - Causal
      evidence from direct electrical stimulation of the hippocampus.
AB  - Auras (focal aware seizure; FAS) are subjective ictal events with retained
      consciousness. Epileptiform activities can disrupt cognitive tasks, but studies
      are limited to seizures with impaired awareness. As a proof of concept, we
      examined the cognitive effects of direct electrical stimulation to the left
      hippocampus which induced a habitual FAS in a patient with left mesial temporal
      lobe epilepsy. During the induced habitual FAS, verbal memory performance
      declined significantly as compared to pre-stimulation testing. Tasks measuring
      auditory working memory and psychomotor processing speed were not affected by the
      stimulation. The study confirms that FAS can impair episodic verbal memory and
      learning.

PMID- 30181953
TI  - PICC-associated infection with Escherichia hermannii: A case report and review of
      the literature.
AB  - Since its identification as a unique species in 1982, Escherichia hermannii has
      been implicated as a pathogenic organism in very few cases of human disease. Our
      report discusses a case of bacteremia with Escherichia hermannii identified by
      Matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) and
      RapIDTM ONE analysis in a patient getting TPN through a peripherally-inserted CVC
      (PICC). The PICC was removed. The bloodstream infection was successfully treated
      with empiric piperacillin-tazobactam, which was then narrowed to trimethoprim
      sulfamethoxazole based on sensitivity data for a 14 day course of antimicrobial
      therapy. E. hermannii's association with bloodstream infection in patients with
      central venous catheters supports data implicating biofilm formation as a key
      pathogenic feature of E. hermannii. Of the 9 previous cases of E. hermannii
      infection reviewed in the literature, 4 cases occurred in immunocompromised
      hosts, 2 were associated with trauma or injection, 2 were associated with central
      lines, and only one case had no identifiable risk factor. E. hermannii appears to
      act as an opportunistic pathogen, causing disease in an immunocompromised host or
      through a central access catheter, injection, or trauma. E. hermannii likely
      causes catheter-related bloodstream infections in these hosts through biofilm
      formation, demonstrating the importance of catheter removal in addition to
      antimicrobial therapy in the treatment of these infections.

PMID- 30181954
TI  - Response to Finsterer and Zarrouk-Mahjoub.

PMID- 30181955
TI  - Molecular and clinical characterization of citrin deficiency in a cohort of
      Chinese patients in Hong Kong.
AB  - BACKGROUND AND OBJECTIVES: This retrospective study analysed a case series of
      subjects with citrin deficiency, and aims to present the molecular and clinical
      characterization of this disease in the Hong Kong Chinese population for the
      first time. PATIENTS AND METHODS: Data from medical records of eighteen patients
      with citrin deficiency (years 2006-2015) were retrieved. Demographic data,
      biochemical parameters, radiological results, genetic testing results,
      management, and clinical outcome were collected and analysed. RESULTS: Eighteen
      patients with diagnosis of citrin deficiency were recruited. All 18 patients
      carried at least one common pathogenic variant c.852_855delTATG in SLC25A13.
      Prolonged jaundice (neonatal intrahepatic cholestasis caused by citrin
      deficiency, NICCD) was the most common presenting symptom, in conjunction with
      elevated plasma citrulline, threonine, alkaline phosphatase, and alpha
      fetoprotein levels. The abnormal biochemical parameters including liver
      derangement returned to normal range in most of the cases by 6 months of age
      after the introduction of a lactose-free formula. There were a few cases with
      atypical presentations. Two subjects did not present with NICCD, and were
      subsequently diagnosed later in life after their siblings presented with symptoms
      of citrin deficiency at one month of age and subsequently received a molecular
      diagnosis. One patient with citrin deficiency also exhibited multiple liver
      hemangioendotheliomas, which subsided gradually after introduction of a lactose
      free formula. Only one patient from this cohort was offered expanded metabolic
      screening at birth. She was not ascertained by conducted newborn screening and
      was diagnosed upon presentation with cholestatic jaundice by 1 month of age.
      CONCLUSION: This is the first report of the clinical and molecular
      characterization of a large cohort of patients with citrin deficiency in Hong
      Kong. The presentation of this cohort of patients expands the clinical phenotypic
      spectrum of NICCD. Benign liver tumors such as hemangioendotheliomas may be
      associated with citrin deficiency in addition to the well-known association with
      hepatocellular carcinoma. Citrin deficiency may manifest in later infancy period
      with an NICCD-like phenotype. Furthermore, this condition is not always
      ascertained by expanded newborn metabolic screening testing.

PMID- 30181956
TI  - Adenomatoid paratesticular tumour - Rare presentation in a child.

PMID- 30181957
TI  - Non-clinical acute and chronic toxicity evaluations of Cissus sicyoides L.
      (Vitaceae) hydroalcoholic leaf extract.
AB  - Cissus sicyoides (Cs) has been traditionally used to treat diabetes and belongs
      to the family Vitaceae, and is known as "vegetable insulin". This study aimed to
      evaluate the acute and chronic non-clinical toxicity of hydroalcoholic extract
      from the leaves of Cissus sicyoides (EHA-Cs). The acute test was performed in
      Wistar rats, administering a single dose of 40.5 mg/kg. Behavioral parameters for
      pharmacological screening were observed to detect signs of Central Nervous System
      activity; consumption of daily food and water, and weight evaluation. After day
      14, the animals were euthanized and blood samples were collected for laboratory
      analyses of hematological and biochemical parameters. The chronic tests were
      administered in doses of 4.5, 13.5 and 40.5 mg/kg. The same parameters were
      observed together with body temperature, glucose, exploration activity (test on
      the open field), and motor activity (diagnostic tests on the Rota-rod). For the
      group given the highest dosage during the study, histopathological examinations
      of vital organs were performed. For acute toxicity, there were no CNS level
      effects, changes in water and food consumption, or hematologic parameters.
      However, there was a significant decrease in weight gain for the treated females.
      Biochemical analyses of the treated animals presented increased levels of AST
      (aspartate aminotransferase) in females, uric acid levels in females and males,
      and amylase in males. In the chronic toxicity tests, water consumption was higher
      for females (at the dosages of 13.5 and 40.5 mg/kg) and for males (at 40.5
      mg/kg). At the dosages of 4.5 and 13.5 mg/kg, feed consumption increased for
      females, while for males it decreased along with weight gain. Blood analysis
      presented an increase in albumin and changes in erythrocytes and hemoglobin for
      males (at the dose of 13.5 mg/kg). Glycemia in females (13.5 mg/kg dose) was
      significantly less, presenting only slight drops at the other doses. The changes
      were reversible in the satellite group. EHA-Cs revealed a relatively low toxicity
      profile (at the popular use dose), and only small changes in hematological and
      biochemical parameters at the dose of 13.5 mg/kg (3x the popular use dosage). In
      addition, EHA-Cs did not promote histological changes in vital organs such as the
      heart, lungs, liver and kidneys.

PMID- 30181958
TI  - Determination of short-chain chlorinated paraffins in multiple matrices of Arctic
      using gas chromatography-electron capture negative ion-low resolution mass
      spectrometry.
AB  - Gas chromatography-electron capture negative ion-low resolution mass spectrometry
      (GC-ECNI-MS) was used for the quantification of short-chain chlorinated paraffins
      (SCCPs) in multiple matrices of Arctic. Samples were spiked with surrogate
      standards (13C10-trans-chlordane) and extracted with dichloromethane and hexane
      (1:1, v/v) using accelerated solvent extraction (ASE). The extract was cleaned
      using a multilayer Silica-Florisil column and epsilon-HCH was added before
      instrument analysis. The SCCPs were analyzed using a gas chromatograph (GC) in
      electron capture negative ion (ECNI) mode coupled with a 7000B triple quadruple
      mass spectrometer (MS) in single quad mode. The calibration is performed using
      three commercial standards (chlorine contents of 51.5%, 55.5%, and 63.0%). A
      reasonable linear correlation for commercial standards was found between chlorine
      content and total response factor (R2  = 0.96). To ensure instrument sensitivity,
      the SCCP congeners were divided into four groups by the optimized combinations
      (C10, C11, C12 and C13) and subjected to analysis by four individual injections.
      This method is suited to analyse the total concentration of SCCPs and individual
      SCCP congener groups in the environmental analysis. * Accelerated solvent
      extraction offers a lower cost of time for per sample and reducing solvent
      consumption. * The presented quantification procedure makes the quantification of
      SCCPs independent from the chlorine content of the used standard mixtures. * The
      samples were subjected to analysis by four individual injections for the
      instrument sensitivity, and the total concentration of SCCPs and CP congener
      groups can be obtained at the same time.

PMID- 30181959
TI  - Method for obtaining the Knudsen diffusion coefficient.
AB  - Recently, we developed a method for obtaining the Knudsen diffusion coefficient
      from the results of tracer experiments with a binary gas system and a porous
      medium in a column. The developed method employs dusty gas model (DGM) equations
      that consider molecular diffusion, nonequimolar fluxes, and Knudsen diffusion.
      The equations derived from the DGM equations for the calculation of the Knudsen
      diffusion coefficient can also be used to obtain the molecular diffusion
      coefficient and the ratio of the Knudsen diffusion coefficients of the two
      chemicals composing the binary gas system. We performed an inversion simulation
      to fit the advection-diffusion equation to the distribution of molar fractions
      determined by mathematically solving the advection-diffusion equation. The
      results confirmed that our method of obtaining the Knudsen diffusion coefficient
      from tracer experiment results yielded accurate values.

PMID- 30181960
TI  - Maximizing the information obtained from chamber-based greenhouse gas exchange
      measurements in remote areas.
AB  - Measurements of greenhouse gas (GHG) fluxes, particularly methane (CH4) and
      nitrous oxide (N2O) in mountain ecosystems are scarce due to the complexity and
      unpredictable behavior of these gases, in addition to the remoteness of these
      ecosystems. In this context, we measured CO2, CH4, and N2O fluxes in four semi
      natural pastures in the Pyrenees to investigate their magnitude and range of
      variability. Our interest was to study GHG phenomena at the patch-level,
      therefore we chose to measure the gas-exchange using a combination of a gas
      analyzer and manual chambers. The analyzer used is a photoacoustic field gas
      monitor that allows multi-gas instantaneous measurements. After implementing
      quality control and corrections, data was of variable quality. We tackled this by
      categorizing data as to providing quantitative or only qualitative information:
      *50% and 59% of all CH4 and N2O data, respectively, provided quantitative
      information above the detection limit.*We chose not to discard data providing
      only qualitative information, because they identify highest- and lowest-flux peak
      periods and indicate the variability of the fluxes, along different altitudes and
      under different climatic conditions.*We chose not to give fluxes below detection
      limit a quantitative value but to acknowledge them as values identifying periods
      with low fluxes.

PMID- 30181961
TI  - Noninvasive Optical Diagnostic Techniques for Mobile Blood Glucose and Bilirubin
      Monitoring.
AB  - Background: People with diabetes need to monitor their blood sugar levels
      constantly and attend health centers regularly for checkups. The aim of this
      study is to provide a healthcare system for mobile blood glucose and bilirubin
      monitoring. Methods: It includes a sensor for noninvasive blood glucose and
      bilirubin measurement using near-infrared spectroscopy and optical method,
      respectively, communicating with a smartphone. Results: It was observed that by
      increasing the glucose concentration, the output voltage of the sensor increases
      in transmittance mode and decreases in reflectance mode. Moreover, it was
      observed that by increasing the bilirubin concentration, the output voltage of
      sensor decreases in transmittance mode and increases in reflectance mode. In the
      collected data there was good correlations between voltage and concentration and
      their relationship were approximately linear. Therefore, it is possible to use
      noninvasive methods to predict the glucose or bilirubin concentration. In vivo
      experiments for glucose were carried out with 19 persons in training phase, and
      five persons were used for testing the model. The glucose behavior model was
      built into the mobile application. The average glucose concentrations from the
      transmittance and reflectance mode were obtained. The average percentage error
      was 8.27 and root mean square error was 18.52 mg/dL. Conclusions: From this
      research, it can be inferred that the noninvasive optical methods implemented on
      wireless sensors and smartphones could form a system that can be used at any time
      and any place in the future as an alternative to traditional invasive blood
      glucose and bilirubin measurement methods.

PMID- 30181962
TI  - Tracheal Sound Analysis for Automatic Detection of Respiratory Depression in
      Adult Patients during Cataract Surgery under Sedation.
AB  - Background: Tracheal sound analysis is a simple way to study the abnormalities of
      upper airway like airway obstruction. Hence, it may be an effective method for
      detection of alveolar hypoventilation and respiratory depression. This study was
      designed to investigate the importance of tracheal sound analysis to detect
      respiratory depression during cataract surgery under sedation. Methods: After
      Institutional Ethical Committee approval and informed patients' consent, we
      studied thirty adults American Society of Anesthesiologists I and II patients
      scheduled for cataract surgery under sedation anesthesia. Recording of tracheal
      sounds started 1 min before administration of sedative drugs using a microphone.
      Recorded sounds were examined by the anesthesiologist to detect periods of
      respiratory depression longer than 10 s. Then, tracheal sound signals converted
      to spectrogram images, and image processing was done to detect respiratory
      depression. Finally, depression periods detected from tracheal sound analysis
      were compared to the depression periods detected by the anesthesiologist.
      Results: We extracted five features from spectrogram images of tracheal sounds
      for the detection of respiratory depression. Then, decision tree and support
      vector machine (SVM) with Radial Basis Function (RBF) kernel were used to
      classify the data using these features, where the designed decision tree
      outperforms the SVM with a sensitivity of 89% and specificity of 97%.
      Conclusions: The results of this study show that morphological processing of
      spectrogram images of tracheal sound signals from a microphone placed over
      suprasternal notch may reliably provide an early warning of respiratory
      depression and the onset of airway obstruction in patients under sedation.

PMID- 30181963
TI  - Performance Investigation of Marginalized Particle-Extended Kalman Filter under
      Different Particle Weighting Strategies in the Field of Electrocardiogram
      Denoising.
AB  - Background: Recently, a marginalized particle-extended Kalman filter (MP-EKF) has
      been proposed for electrocardiogram (ECG) signal denoising. Similar to particle
      filters, the performance of MP-EKF relies heavily on the definition of proper
      particle weighting strategy. In this paper, we aim to investigate the performance
      of MP-EKF under different particle weighting strategies in both stationary and
      nonstationary noises. Some of these particle weighting strategies are introduced
      for the first time for ECG denoising. Methods: In this paper, the proposed
      particle weighting strategies use different mathematical functions to regulate
      the behaviors of particles based on noisy measurements and a synthetic ECG signal
      built using feature parameters of ECG dynamic model. One of these strategies is a
      fuzzy-based particle weighting method that is defined to adapt its function based
      on different input signal-to-noise ratios (SNRs). To evaluate the proposed
      particle weighting strategies, the denoising performance of MP-EKF was evaluated
      on MIT-BIH normal sinus rhythm database at 11 different input SNRs and in four
      different types of artificial and real noises. For quantitative comparison, the
      SNR improvement measure was used, and for qualitative comparison, the multi-scale
      entropy-based weighted distortion measure was used. Results: The experimental
      results revealed that the fuzzy-based particle weighting strategy exhibited a
      very well and reliable performance in both stationary and nonstationary noisy
      environments. Conclusion: We concluded that the fuzzy-based particle weighting
      strategy is the best-suited strategy for MP-EKF framework because it adaptively
      and automatically regulates the behaviors of particles in different noisy
      environments.

PMID- 30181964
TI  - An Optimized Framework for Cancer Prediction Using Immunosignature.
AB  - Background: Cancer is a complex disease which can engages the immune system of
      the patient. In this regard, determination of distinct immunosignatures for
      various cancers has received increasing interest recently. However, prediction
      accuracy and reproducibility of the computational methods are limited. In this
      article, we introduce a robust method for predicting eight types of cancers
      including astrocytoma, breast cancer, multiple myeloma, lung cancer,
      oligodendroglia, ovarian cancer, advanced pancreatic cancer, and Ewing sarcoma.
      Methods: In the proposed scheme, at first, the database is normalized with a
      dictionary of normalization methods that are combined with particle swarm
      optimization (PSO) for selecting the best normalization method for each feature.
      Then, statistical feature selection methods are used to separate discriminative
      features and they were further improved by PSO with appropriate weights as the
      inputs of the classification system. Finally, the support vector machines,
      decision tree, and multilayer perceptron neural network were used as classifiers.
      Results: The performance of the hybrid predictor was assessed using the holdout
      method. According to this method, the minimum sensitivity, specificity,
      precision, and accuracy of the proposed algorithm were 92.4 +/- 1.1, 99.1 +/-
      1.1, 90.6 +/- 2.1, and 98.3 +/- 1.0, respectively, among the three types of
      classification that are used in our algorithm. Conclusion: The proposed algorithm
      considers all the circumstances and works with each feature in its special way.
      Thus, the proposed algorithm can be used as a promising framework for cancer
      prediction with immunosignature.

PMID- 30181965
TI  - Bacterial Bioprinting on a Flexible Substrate for Fabrication of a Colorimetric
      Temperature Indicator by Using a Commercial Inkjet Printer.
AB  - Background: Bacterial sensors are recommended for medical sciences,
      pharmaceutical industries, food industries, and environmental monitoring due to
      low cost, high sensitivity, and appropriate response time. There are some
      advantages of using bacterial spores instead of bacteria in vegetative forms as
      spores remain alive without any nutrient for a long time and change to vegetative
      form when a suitable environment is provided for them. Methods: For biosensor
      fabrication, it is important to define how the bacterial spores are delivered to
      the substrate media. The main purpose of this paper is an investigation of
      transferring bacterial spores on a flexible substrate media using a commercial
      inkjet printer (HP Deskjet 1510). It should be noted that in the previous
      researches, the special printers were used to transfer bacteria on rigid films.
      Results: These printed bacterial spores are used as a colorimetric temperature
      indicator. The custom-made bio-inks are prepared by bacterial spores along with a
      gelling agent and pH indicator. Conclusions: Finally, transformation of bacterial
      spores into vegetative bacteria is occurred by changing of temperature. A color
      change in the bio-prints is demonstrated because the bacterial transformation and
      growth change the environmental pH to an acidic level.

PMID- 30181966
TI  - Photoneutron Dose Estimation in GRID Therapy Using an Anthropomorphic Phantom: A
      Monte Carlo Study.
AB  - Background: In the past, GRID therapy was used as a treatment modality for the
      treatment of bulky and deeply seated tumors with orthovoltage beams. Now and with
      the introduction of megavoltage beams to radiotherapy, some of the radiotherapy
      institutes use GRID therapy with megavoltage photons for the palliative treatment
      of bulky tumors. Since GRID can be a barrier for weakening the photoneutrons
      produced in the head of medical linear accelerators (LINAC), as well as a
      secondary source for producing photoneutrons, therefore, in terms of radiation
      protection, it is important to evaluate the GRID effect on photoneutron dose to
      the patients. Methods: In this study, using the Monte Carlo code MCNPX, a full
      model of a LINAC was simulated and verified. The neutron source strength of the
      LINAC (Q), the distributions of flux (phi), and ambient dose equivalent (H*[10])
      of neutrons were calculated on the treatment table in both cases of with/without
      the GRID. Finally, absorbed dose and dose equivalent of neutrons in some of the
      tissues/organs of MIRD phantom were computed with/without the GRID. Results: Our
      results indicate that the GRID increases the production of the photoneutrons in
      the LINAC head only by 0.3%. The calculations in the MIRD phantom show that
      neutron dose in the organs/tissues covered by the GRID is on average by 48% lower
      than conventional radiotherapy. In addition, in the uncovered organs (by the
      GRID), this amount is reduced to 25%. Conclusion: Based on the findings of this
      study, in GRID therapy technique compared to conventional radiotherapy, the
      neutron dose in the tissues/organs of the body is dramatically reduced.
      Therefore, there will be no concern about the GRID effect on the increase of
      unwanted neutron dose, and consequently the risk of secondary cancer.

PMID- 30181967
TI  - Employing the Local Radon Transform for Melanoma Segmentation in Dermoscopic
      Images.
AB  - In recent years, the number of patients suffering from melanoma, as the deadliest
      type of skin cancer, has grown significantly in the world. The most common
      technique to observe and diagnosis of such cancer is the use of noninvasive
      dermoscope lens. Since this approach is based on the expert ocular inference,
      early stage of melanoma diagnosis is a difficult task for dermatologist. The main
      purpose of this article is to introduce an efficient algorithm to analyze the
      dermoscopic images. The proposed algorithm consists of four stages including
      converting the image color space from the RGB to CIE, adjusting the color space
      by applying the combined histogram equalization and the Otsu thresholding-based
      approach, border extraction of the lesion through the local Radon transform, and
      recognizing the melanoma and nonmelanoma lesions employing the ABCD rule.
      Simulation results in the designed user-friendly software package environment
      confirmed that the proposed algorithm has the higher quantities of accuracy,
      sensitivity, and approximation correlation in comparison with the other state-of
      the-art methods. These values are obtained 98.81 (98.92), 94.85 (89.51), and
      90.99 (86.06) for melanoma (nonmelanoma) lesions, respectively.

PMID- 30181968
TI  - Different Dosimeters/Detectors Used in Small-Field Dosimetry: Pros and Cons.
AB  - With the advent of complex and precise radiation therapy techniques, the use of
      relatively small fields is needed. Using such field sizes can cause uncertainty
      in dosimetry; therefore, special attention is required both in dose calculations
      and measurements. There are several challenges in small-field dosimetry such as
      the steep gradient of the radiation field, volume averaging effect, lack of
      charged particle equilibrium, partial occlusion of radiation source, beam
      alignment, and unable to use a reference dosimeter. Due to these challenges,
      special dosimeters are needed for small-field dosimetry, and this review article
      discusses this topic.

PMID- 30181969
TI  - What's New in Critical Illness and Injury Science?: Revalidation of vasoactive
      ventilation-renal scoring in predicting outcome in postcardiac surgery children
      and the importance of replicating studies.

PMID- 30181970
TI  - Acute care for the three leading causes of mortality in lower-middle-income
      countries: A systematic review.
AB  - According to the World Health Organization, the three leading causes of mortality
      in lower-middle-income countries (LMIC) are ischemic heart disease (IHD), stroke,
      and lower respiratory infections (LRIs), causing 111.8, 68.8, and 51.5 annual
      deaths per 100,000, respectively. Due to barriers to healthcare, patients
      frequently present in critical stages of these diseases. Measured implementations
      in critical care in LMIC have been published; however, the literature has not
      been formally reviewed. We performed a systematic review of the literature
      indexed in PubMed as of October 2017. Abstracts were limited to human studies in
      English, French, and Spanish, conducted in LMIC, and containing quantitative data
      on acute care of IHD, stroke, and LRI. The search resulted in 4994 unique
      abstracts. Through multiple rounds of screening using criteria determined a
      priori, 161 manuscripts were identified: 38 for IHD, 20 for stroke, 26 for adult
      LRI, and 78 for pediatric LRI. These studies, predominantly from Asia,
      demonstrate successful diagnostic and treatment measures used in providing acute
      care for patients in LMIC. Given that, only four manuscripts originated in
      Central or South America, original research from these areas is lacking. IHD,
      stroke, and LRIs are significant causes of mortality, especially in LMIC.
      Diagnostic and therapeutic interventions for IHD (monitoring, medications,
      thrombolytics, percutaneous intervention, coronary artery bypass graft), stroke
      (therapeutic hypothermia, medications, and thrombolytics), and LRI (oxygen
      saturation measurement, diagnostic ultrasound, administration of oxygen,
      appropriate antibiotics, and other medications) have been studied in LMIC and
      published.

PMID- 30181971
TI  - Vasoactive-ventilation-renal score in predicting outcome postcardiac surgery in
      children.
AB  - Objective: The objective of this study was to evaluate vasoactive-ventilation
      renal (VVR) score to predict outcome postcardiac surgery in children and
      establish the time at which the score is best to predict outcome. Materials and
      Methods: This prospective cohort included children <=18 years recovering from
      cardiac surgery for congenital heart disease. Data were collected from the
      Intensive Care Unit (ICU) and vasoactive-inotropic score (VIS) and VVR scores
      calculated at admission, 24 h, and 48 h postoperatively. Outcome of interest was
      prolonged length of ICU stay (defined as length of stay [LOS] in the upper 25th
      percentile) and ICU mortality. Correlation between the outcome and scores was
      obtained and receiver operating characteristic (ROC) curves generated.
      Independent association of the scores with the outcome was also established.
      Results: One thousand ninety-seven patients were enrolled with a median age of 24
      months (range: 2 days-18 years) including 14.6% with single ventricle physiology.
      Pediatric ICU LOS >89 h was considered prolonged, and mortality was 2.2%. VVR
      score correlated better with outcome and had greater area under the curve (AUC)
      for ROC curve than the corresponding VIS at each study time point. The AUC of ROC
      curve for VVR score was greatest at 48 h for predicting both prolonged LOS (0.87)
      and mortality (0.92). VVR score at 48 h remains strongly associated with both
      prolonged LOS (odds ratio [OR] - 1.24; P = 0.000) and mortality (OR - 1.16; P =
      0.000). Conclusion: VVR score is effective and robust bedside method to predict
      prolonged LOS and mortality postpediatric cardiac surgery. VVR score at 48 h was
      the best to predict outcome.

PMID- 30181972
TI  - The relationship between fluid resuscitation and intra-abdominal hypertension in
      patients with blunt abdominal trauma.
AB  - Background: Excessive fluid administration for saving patients from hypovolemic
      shocks is one of the main causes of intra-abdominal hypertension (IAH) and
      abdominal compartment syndrome (ACS). The purpose of this paper is to survey the
      relationship between fluid resuscitation and increase intra-abdominal pressure
      (IAP). Materials and Methods: The present descriptive-analytical study recruited
      100 patients with confirmed abdominal trauma and presenting to emergency
      departments. The cases with high IAP measured through the bladder were identified
      as developing ACS in case of having comorbidities involving two of the following
      systems: respiratory system, renal system or cardiovascular system. The volume of
      the fluids administered was compared in the first 24 h in subjects with and
      without ACS. Results: Of 100 patients with abdominal trauma, whose IAP was
      measured, 28 cases developed ACS. The mean volume of the fluids received was
      found to be significantly higher in the patients with ACS (8772 ml) compared to
      in those without (5404 ml). As a complication of excessive fluid administration,
      IAH can seriously threaten the patient's life. Conclusions: Excessive fluid
      resuscitation causes ACS among the critically ill or injured patients such as
      abdominal trauma, pelvic fracture and intra-abdominal organ injuries hence to
      prevent this complication in all patients requiring short-term excessive
      administration of fluids, great care, and sensitivity are required to constantly
      control IAP and adjust the fluid administration.

PMID- 30181973
TI  - The acute care diagnostics collaboration: Performance assessment of contrast
      enhanced ultrasound compared to abdominal computed tomography and conventional
      ultrasound in an emergency trauma score bayesian clinical decision scheme.
AB  - Background: Bayes' theorem describes the probability of an event, based on
      conditions that might be related to the event.[1] We developed the Bayesian
      Diagnostic Gains (BDG) method as a simple tool for interpreting diagnostic
      impact.[234567]. Aim: We aimed to evaluate the clinical diagnostic impact of
      contrast-enhanced ultrasound (CEUS) compared to traditional abdominal computed
      tomography (CT) and standard ultrasound (US) in a Bayesian Clinical Decision
      Scheme. Materials and Methods: Our mathematical method uses Bayesian Diagnostic
      Gains (BDG) model. For the purposes of our model, the EMTRAS was used as pretest
      probability and stratified as low risk (0-3 points = 10%), moderate risk (4-6
      points = 42%), and high risk (7-12 points = 80%) based on mortality risk.
      Sensitivity and specificity for US, CT, and CEUS were obtained from pooled data
      and used to calculate LR- and LR+. Bayesian/Fagan nomogram was used to attain
      posttest probabilities using baseline probability of an event on the first axis
      (PRE), with LR on the second axis, and read off the pos-test probability (POST)
      on the third axis. For the nomogram analysis, the pretest probability (Pre)
      scoring for the EMTRAS score was obtained using the original EMTRAS data.
      Posttest probabilities were obtained based on the Bayes/Fagan Nomgram. Relative
      diagnostic gain (RDG) and absolute diagnostic gain (ADG) were calculated based on
      the differences deducted from pre- and post-test probabilities. IBM(r) SPSS(r)
      Statistics 20 was used for analysis and modeling. ANOVA was used for association
      between EMTRAS, CT scan, and CEUS, where P value set at 0.05. Results: Pooled
      data for Sensitivity (Se), Specificity (Sp), LR+, and LR- were obtained for US
      (Se = 45.7%, Sp = 91.8%, LR+ = 5.57, and LR- = 0.59), CEUS (Se 91.4%, Sp 100%,
      LR+ 91, and LR-0.09), and CT (Se = 94.8%, SP = 98.7%, LR+ = 73, and LR- =0.05).
      ANOVA analysis for LR+ and LR- showed no significant difference (P < 0.8745 and P
      < 0.9841). Comparison of CT and CEUS did not yield statistically significant
      differences for LR+ (P < 0.1). Conclusion: In this Bayesian model, the diagnostic
      performance of CEUS was found to be similar to traditional abdominal CT. The
      greatest diagnostic gain was observed in low pretest positive LR groups.

PMID- 30181974
TI  - Inferior vena cava diameter as a guide in hypotensive patients for appropriate
      saline therapy: An observational study.
AB  - Background: Knowledge of intravascular volume (IV) status of a hypotensive
      patient is of utmost importance. Clinical evaluation and central venous pressure
      (CVP) measurement are routinely used as a guide for evaluation of IV in these
      patients. However, clinical assessment may be inaccurate, and CVP measurement is
      invasive. Moreover, CVP changes slowly with saline therapy, which is unfavorable
      for fluid resuscitation. Aim: Our aim is to find the correlation and sensitivity
      of inferior vena cava (IVC) diameter measured by ultrasound to provide a
      noninvasive method for evaluation of IV among patients with hypotension and
      hypovolemia in the emergency department (ED). Methods: We measured the IVC
      diameter of hypotensive patients before and after saline therapy. As all of the
      patients had central venous line (CV-line) in place, CVP was also measured before
      and after. Using MedCalc and SPSS software the correlation between these two was
      determined as expressed with "r." Then, receiver operating characteristic (ROC)
      curve was sketched. Results: Ninety-nine patients, 49 (49.5%) males, were
      evaluated. Mean systolic blood pressure was 90 mmHg with a mean hazard ratio
      about 104. IVC diameter was 7.44 +/- 5.13 mm before and 9.84 +/- 5.29 after (P =
      0.002) saline therapy. There was a high correlation between IVC diameter and CVP
      (r = 0.941, P < 0.0001 before saline therapy and r = 0.95, P < 0.0001 after
      saline therapy). ROC curve for IVC diameter shows a very high sensitivity for all
      criteria values. Conclusion: IVC diameter measurement using ultrasonography has
      excellent correlation with CVP. This method is very sensitive to rapid IV changes
      thus useful to guide saline therapy in hypotensive patients referred to ED.
      However, its use in certain subsets of patients' needs further studies.

PMID- 30181975
TI  - Prognostic significance of nonthyroidal illness syndrome in critically ill adult
      patients with sepsis.
AB  - Aim: This study was performed to investigate the association of non-thyroidal
      illness syndrome (NTIS) with 28-day mortality in adults with sepsis. Methods: We
      performed a prospective observational analysis of adult patients with sepsis.
      Patients' demographic data, comorbidities, the blood test results including
      thyroid hormone analysis at admission, Acute Physiologic and Chronic Health
      Evaluation II score and Sequential Organ Failure Assessment score were compared
      between 28-day survivors and non-survivors. Further patients were divided into 3
      groups; non-NTIS, NTIS group A (low total tri-iodothyronine (T3) and NTIS group B
      (low T3 with low thyroxine (T4). Multivariate Cox proportional hazards regression
      analysis was performed to determine the risk factors for mortality. Results: A
      total of 360 patients were included, and overall mortality was 30%. The mortality
      of non-NTIS patients was 13.4%; group A, 50.1%, and group B 69.1% (P < .001). The
      median T3 (IQR) in non-survivors and survivors was 0.74 (0.56-1.17) and1.58 (0.91
      2.13) and median free T3 (IQR) 2.40 (1.13-3.01) and 4.03 (3.03-7.13) respectively
      (P < .001). In Cox proportional hazards analysis, NTIS group A (hazard ratio,
      1.66; 95% confidence interval [CI], 1.00-2.76) and group B (hazard ratio, 2.57;
      95% CI, 1.53-4.34). The area under the receiver-operating curve of NTIS groups
      was 0.68 (95% CI, 0.63-0.72). Conclusion: The T3 and free T3 were significantly
      lower in non-survivors compared with that in survivors and that a combination of
      low T3 with low T4 was associated with greater mortality than low T3 alone. A
      lower free T3 is independently associated with 28-day mortality.

PMID- 30181976
TI  - Multidrug-resistant Burkholderia cepacia bacteremia in an immunocompetent adult
      diagnosed with dengue and scrub coinfection: A rare case report.
AB  - Burkholderia cepacia is an opportunistic nosocomial pathogen causing infections
      in immunocompromised hosts. Infection by Burkholderia in an immunocompetent host
      is a rare entity. We report a case of dengue and scrub coinfection complicated by
      B. cepacia bloodstream infection along with literature review of such infections
      in immunocompetent adults. Before the introduction of automated technologies, it
      was difficult to differentiate this organism from other aerobic Gram-negative
      nonfermenters, which have different intrinsic resistance profiles. Furthermore,
      Burkholderia has intrinsic as well as acquired resistance to various
      antimicrobials but not commonly to ceftazidime. To our knowledge, ours is the
      first case of multidrug-resistant B. cepacia infection in an immunocompetent host
      to be reported till date.

PMID- 30181977
TI  - Massive air embolism while removing a central venous catheter.
AB  - Air embolism is a rare but mostly iatrogenic complication of medical or surgical
      procedures and may have a serious outcome. On the removal of a central venous
      catheter (CVC), minor carelessness can lead to a venous air embolism sometimes
      accompanied by arterial embolism. We experienced the case of a 61-year-old male
      who suffered from a paradoxical systemic air embolism while we removed a CVC.
      Immediate resuscitation and venovenous extracorporeal membrane oxygenation
      support saved his life. Multiple end-organ damage related to the systemic air
      embolism was noted, including the kidney, liver, and brain. In echocardiography,
      multiple air bubbles and an atrial septal defect were observed. An air embolism
      is preventable with appropriate precautions and techniques. Therefore, it is
      important to identify errors and prevent occurrence.

PMID- 30181978
TI  - Undiagnosed autoimmune hepatitis causing prolonged mechanical ventilation.

PMID- 30181979
TI  - The importance of basic and engineering sciences for next generation research in
      the field of oral and maxillofacial surgery.

PMID- 30181980
TI  - Dental management of patients on anti-thrombotic agents.
AB  - The number of geriatric patients seeking dental service is ever-rising because of
      increased life expectancy, also with problem of increased chronic medical
      conditions. One of them are patients on anti-thrombotic medication. Bleeding
      complication after minor oral surgery by anti-thrombotic agents is of concerns to
      dentists on dental management of these patients. Risk and benefit of the anti
      thrombotic agents must be weighed before initiating dental procedures, which
      should be established as a treatment guideline. Purpose of the paper is to
      optimize the management of the dental patients on anti-thrombotic medication via
      standardization of treatment protocol of such a patient.

PMID- 30181981
TI  - Zygomaticomaxillary buttress and its dilemma.
AB  - Zygomatic fractures are the second most common fractures of the facial skeleton,
      after nasal bone fractures. Due to its uniqueness, the malar bone plays a very
      important role in maintaining appropriate facial contours. Zygomatic fractures
      can cause ocular and mandibular functional impairment, along with cosmetic
      defects. With the help of advanced imaging techniques and various treatment
      options, the management of zygomatic fractures has become more sophisticated and
      less invasive. This article discusses zygomatic fractures in detail: their
      clinical and radiographic features, and the various treatment options available.

PMID- 30181982
TI  - A comparative study of immediate wound healing complications following cleft lip
      repair using either absorbable or non-absorbable skin sutures.
AB  - Objectives: The aim of the study was to compare wound healing complications
      following the use of either absorbable or non-absorbable sutures for skin closure
      in cleft lip repair. Materials and Methods: This was a randomized controlled
      trial conducted at the Department of Oral and Maxillofacial Surgery, Lagos
      University Teaching Hospital, Idi Araba, Lagos State, Nigeria. Sixty subjects who
      required either primary or secondary cleft lip repair and satisfied all the
      inclusion criteria were recruited and randomized into two groups (Vicryl group or
      Nylon group). The surgical wounds in all subjects were examined on 3rd, 7th, and
      14th postoperative days (POD) for presence or absence of tissue reactivity, wound
      dehiscence, and local wound infection. Results: Hemorrhage, tissue reactivity,
      wound dehiscence, and local wound infection were identified as wound healing
      complications following cleft lip repair. The incidence of postoperative wound
      healing complications on POD3 was 33.3%. Tissue reactivity was more common
      throughout the evaluation period with the use of an absorbable (Vicryl) suture
      compared to a non-absorbable (Nylon) suture, although the difference was
      statistically significant only on POD7 (P=0.002). There were no significant
      differences in the incidences of wound dehiscence and infection between the two
      groups throughout the observation period. Conclusion: There were no statistically
      significant differences in the incidences of wound dehiscence and surgical site
      wound infection following the use of either Vicryl or Nylon for skin closure
      during cleft lip repair. However, more cases of tissue reactivity were recorded
      in the Vicryl group than in the Nylon group on POD7. Particular attention must be
      paid to detect the occurrence of wound healing complications, most especially
      tissue reactivity, whenever a Vicryl suture is used for skin closure in cleft lip
      repair.

PMID- 30181983
TI  - Anatomical position of the mandibular canal in relation to the buccal cortical
      bone: relevance to sagittal split osteotomy.
AB  - Objectives: Classification of the degree of postoperative nerve damage according
      to contact with the mandibular canal and buccal cortical bone has been studied,
      but there is a lack of research on the difference in postoperative courses
      according to contact with buccal cortical bone. In this study, we divided
      patients into groups according to contact between the mandibular canal and the
      buccal cortical bone, and we compared the position of the mandibular canal in the
      second and first molar areas. Materials and Methods: Class III patients who
      visited the Dankook University Dental Hospital were included in this study. The
      following measurements were made at the second and first molar positions: (1)
      length between the outer margin of the mandibular canal and the buccal cortical
      margin (a); (2) mandibular thickness at the same level (b); (3) Buccolingual
      ratio=(a)/(b)*100; and (4) length between the inferior margin of the mandibular
      canal and the inferior cortical margin. Results: The distances from the canal to
      the buccal bone and from the canal to the inferior bone and mandibular thickness
      were significantly larger in Group II than in Group I. The buccolingual ratio of
      the canal was larger in Group II in the second molar region. Conclusion: If
      mandibular canal is in contact with the buccal cortical bone, the canal will run
      closer to the buccal bone and the inferior border of the mandible in the second
      and first molar regions.

PMID- 30181984
TI  - Prognostic factors for outcome of surgical treatment in medication-related
      osteonecrosis of the jaw.
AB  - Objectives: The number of patients with medication-related osteonecrosis of the
      jaw (MRONJ) is increasing, but treatment remains controversial. Published papers
      and systematic reviews have suggested that surgical treatment is effective in
      patients with MRONJ. The purpose of this study was to determine whether
      preoperative University of Connecticut Osteonecrosis Numerical Scale (UCONNS),
      other serologic biomarkers, and size of necrosis are prognostic factors for
      outcome of surgical treatment in MRONJ. Materials and Methods: From January 2008
      to December 2016, 65 patients diagnosed with MRONJ at the Department of Oral and
      Maxillofacial Surgery in College of Dentistry, Dankook University who required
      hospitalization and surgical treatment were investigated. Patient information,
      systemic factors, and UCONNS were investigated. In addition, several serologic
      values were examined through blood tests one week before surgery. The size of
      osteolysis was measured by panoramic view and cone-beam computed tomography in
      all patients. With this information, multivariate logistic regression analysis
      with backward elimination was used to examine factors affecting postoperative
      outcome. Results: In multivariate logistic analysis, higher UCONNS, higher C
      reactive protein (CRP), larger size of osteolysis, and lower serum alkaline
      phosphate were associated with higher incidence of incomplete recovery after
      operation. This shows that UCONNS, CRP, serum alkaline phosphate, and size of
      osteolysis were statistically significant as factors for predicting postoperative
      prognosis. Conclusion: This study demonstrated that CRP, UCONNS, serum alkaline
      phosphate, and size of osteolysis were statistically significant factors in
      predicting the prognosis of surgical outcome of MRONJ. Among these factors,
      UCONNS can predict the prognosis of MRONJ surgery as a scale that includes
      various influencing factors, and UCONNS should be used first as a predictor. More
      aggressive surgical treatment and more definite surgical margins are needed when
      the prognosis is poor.

PMID- 30181985
TI  - Role of E-cadherin and cyclin D1 as predictive markers of aggression and clonal
      expansion in head and neck squamous cell carcinoma.
AB  - Objectives: Head and neck squamous cell carcinoma (HNSCC) is the sixth most
      common malignancy worldwide. Inconsistency in various histopathologic features
      for predicting nodal metastasis and overall prognosis and a better understanding
      of molecular mechanisms of tumourigenesis have shifted the focus to a search for
      more definitive predictive markers. To identify the role of two
      immunohistochemical (IHC) markers, E-cadherin and cyclin D1, as predictive
      markers of aggressiveness in HNSCC and to assess clonal expansion of tumour
      cells. Materials and Methods: A total of 66 cases of HNSCC with neck node
      dissection were studied. IHC was performed on primary tumour sections and lymph
      nodes showing metastatic deposits. Histopathological parameters such as tumour
      grade and TNM stage together with nodal status were compared according to
      expression of the two markers. Fischer's chi-square test was used to assess the
      correlation between the two markers and histopathological parameters. Results:
      Out of 66 cases studied, 37 showed LN metastasis. Most of the patients were male,
      and the most common tumour site was buccal mucosa. We found a significant
      association between loss of E-cadherin and node metastasis (P<0.001) and higher
      TNM stage (P<0.001). Cyclin D1 overexpression was significantly associated with
      only nodal metastasis (P=0.007). No significant association with tumour grade was
      found for either marker. The subgroup of E-cadherin loss with cyclin D1
      overexpression was associated with the maximum incidence of nodal metastasis and
      higher TNM stage, highlighting the importance of using a combination of these two
      markers. A significant association was noted between the expression of markers at
      the primary site and at nodal deposits, indicating clonal expansion. Conclusion:
      A combination of the two markers E-cadherin and cyclin D1 can predict prognosis
      in HNSCC, although tumour heterogeneity may affect this association in some
      cases.

PMID- 30181986
TI  - Nasolabial and extended nasolabial flaps for reconstruction in oral submucous
      fibrosis.
AB  - Objectives: The objective of the study was to evaluate the results of
      nasolabial/extended nasolabial flaps as a modality for treatment of oral
      submucous fibrosis. Materials and Methods: Eleven patients of Stage III or IVa
      maximum interincisal opening were selected to be operated. Nasolabial/extended
      nasolabial flaps were done for both the sides. All of the flaps were done in a
      single stage and were inferiorly based. A similar flap harvest/surgical technique
      was utilized for all the cases. Results: The preoperative mouth opening ranged
      from 5 to 16 mm, with a mean of 10.09 mm. At 6 months the mouth opening ranged
      from 29 to 39 mm. Some of the complications encountered were poor scar, wisdom
      tooth traumatising the flap, decreased mouth opening due to non compliance and
      too much bulk. All of theses were managed satisfactorily. Conclusion: The
      nasolabial flap is a very reliable flap to restore the function of oral cavity.
      Important adjuvant measures are habit cessation, lifestyle changes, and
      aggressive physiotherapy.

PMID- 30181987
TI  - Classical oral manifestations of Dyke-Davidoff-Masson syndrome: a case report
      with review of the literature.
AB  - Dyke-Davidoff-Masson syndrome is a non-inherited rare condition that presents
      during childhood and is characterized by seizures, hemiplegia, mental
      retardation, cerebral hemiatrophy, calvarial thickening, and hyperpneumatization
      of the frontal sinuses. The present article highlights a case of a 12-year-old
      male child with additional clinical findings of cafe-au-late pigmentation and
      ocular lipodermoid. This is the first case report of Dyke-Davidoff-Masson
      syndrome to describe oral manifestations, such as unilateral delayed eruption of
      teeth, hypoplasia, and taurodontism, which could be unique and characteristic of
      this condition. Oral health care providers and physicians should be aware of
      these oral observations as dental referrals could warrant early dental
      prophylactic care and can be useful in diagnosing the possible time of injury and
      type of Dyke-Davidoff-Masson syndrome.

PMID- 30181988
TI  - Corrigendum: Responses of the Differentiated Intestinal Epithelial Cell Line Caco
      2 to Infection With the Giardia intestinalis GS Isolate.
AB  - [This corrects the article DOI: 10.3389/fcimb.2018.00244.].

PMID- 30181989
TI  - Corrigendum: Iron Acquisition Mechanisms and Their Role in the Virulence of
      Burkholderia Species.
AB  - [This corrects the article DOI: 10.3389/fcimb.2017.00460.].

PMID- 30181990
TI  - Scientometric Study on Non-communicable Diseases in Iran: A Review Article.
AB  - Background: Non-Communicable disease (NCDs) is a killer of people that needs to
      urgent actions across the world. Scientific evidence is the critical arm for
      effective interventions. Therefore, we aimed to quantify the trend of four main
      NCDs' scientific publication in a 17-yr period, and reflect international
      collaboration. Methods: This scientometric study on four main NCDs;
      cardiovascular diseases, cancers, diabetes, and chronic respiratory diseases were
      carried out through the narrative review in international databases of Scopus
      from 2000 to 2016. In this way, the number of articles, citations, and
      international collaboration were assessed, and the frequently used terms on
      noncommunicable diseases were mapped by VOSviewer software. Results: Over the 17
      years, 25827 articles about four main NCDs by Iran indexed in Scopus have
      increasing trend steadily. However, chronic obstructive respiratory publications
      have slow trend. The number of articles, citations, and h index of cancer-related
      publications was higher than the others. Diabetes, cardiovascular diseases, and
      chronic respiratory diseases scientometrics indicators state in next positions,
      respectively. The most collaborative country was USA in the four areas, and there
      was not seen region countries' collaboration in top ten levels. The frequently
      used terms in NCDs' articles in order were diabetes, cardiovascular diseases, and
      breast cancer. Conclusion: Iran provides appropriate face of cancer, diabetes,
      and cardiovascular diseases publications in the mirror of NCDs' scientometry.
      However, there is need for more effort in chronic respiratory diseases
      researches, and strengthen collaboration with regional countries.

PMID- 30181991
TI  - The Prevalence and Trends of Hepatitis B, Hepatitis C, and HIV among Voluntary
      Blood Donors in Kohgiluyeh and Boyer-Ahmad Transfusion Center, Southwestern Iran.
AB  - Background: Transfusion transmissible infections (TTIs) are a common complication
      of blood transfusion. Evaluation and monitoring the prevalence rate of TTIs in
      blood donors is a valuable indicator of donor selection and blood safety. We
      analyzed the trends of these infections among blood donors at Kohgiluyeh and
      Boyer-Ahmad transfusion service (KBTC) during 10 years. Methods: Viral screening
      and confirmatory tests were carried out on 180304 voluntary donations from 2005
      2014. The annual prevalence rates of hepatitis B virus (HBV), hepatitis C virus
      (HCV) and HIV infections per 100000 donations and 95% confidence interval were
      calculated. Chi-square test was applied to obtain the P-value. Results: The
      overall prevalence was 0.13% for HBV and 0.06% for HCV while there were only
      three positive cases for HIV. The annual trend fluctuated during the time period
      studied. Compared to first-time donors, regular and repeat donors were
      significantly less likely to be positive for these infections. Outstandingly,
      this study provides first data in TTIs seropositivity rates among blood donors in
      our region; surprisingly were lower compared to other reports of Iran.
      Conclusion: The trends of TTIs prevalence in this study provide additional
      evidence that safety measures employed by the KBTC have been effective in
      maintaining a safe blood supply. The lower prevalence of TTIs in our study
      compared with other Iranian studies and also the general population reflects the
      efficacy of donor selection and education procedures in KBTC.

PMID- 30181992
TI  - Comparison of Ticagrelor and Clopidogrel for Patients Undergoing Emergency
      Percutaneous Coronary Intervention.
AB  - Background: We compared treatments with the antiplatelets ticagrelor and
      clopidogrel used in patients with acute myocardial infarction (AMI) during the
      perioperative period for emergency percutaneous coronary intervention (PCI).
      Methods: A total of 120 patients were selected and randomly divided into control
      and observation groups (60 patients in each) from 2014-2016 at The Affiliated
      Hospital of Qingdao University. The patients in the control group received 300 mg
      clopidogrel and 300 mg aspirin for oral administration, while those in the
      observation group were given 180 mg ticagrelor and 300 mg aspirin orally prior to
      the PCI. During the operation, heparinization and a tirofiban micro-pump were
      used continuously. Results: Coronary artery and peripheral venous blood were
      extracted from each patient to obtain various parameters of thrombelastogram
      (TEG), and the maximum platelet aggregation rates in order to compare
      antiplatelet effects. Major adverse cardiac events (MACE) were recorded during
      the following 6-month follow-up. Analysis of the data showed no differences in
      terms of the time span between medication intake and stent implantation, or the
      dosage of heparin and tirofiban used between the two groups. Before stent
      implantation, and 24 and 48 h after the procedure the average R and K values of
      TEG in coronary artery blood and peripheral venous blood samples in the
      observation group were longer than those in the control group, while the alpha
      angle, MA, CI, MARAA and MARADP values were lower (P<0.05). Conclusion:
      Ticagrelor can improve antiplatelet treatment for patients with AMI during the
      perioperative period of emergency PCI.

PMID- 30181993
TI  - Lack of Dietary Diversity Contributes to the Gaps in Micronutrient Status and
      Physical Development between Urban and Rural Infants.
AB  - Background: Although the prevalence of malnutrition among Chinese infants has
      decreased, micronutrient deficiency is still common. This study aimed to describe
      and compare the status of micronutrient deficiency and its association with
      dietary variety and socio-demographic features among infants from urban and rural
      China. Methods: A cross-sectional study was performed on 1200 children aged 18
      month-old from rural villages in Yunnan and an urban city in Shanghai.
      Information on food intake was obtained from a 24-h dietary recall technique.
      Anthropometric measures, dietary diversity score (DDS), food variety score (FVS),
      and mean adequacy ratio (MAR) were calculated and compared. Correlations between
      DDS, FVS, MAR, NAR, and anthropometric measures were examined. Results: Compared
      with urban area, DDS, FVS, and NAR of most micronutrients of infants from rural
      areas were significantly lower. These data corresponded to significant lower Z
      scores of physical growth in rural infants. DDS, FVS, and NAR were positively
      correlated to anthropometric measures. Conclusion: Infants from rural areas
      consumed a significantly lower amount of micronutrient and had worse
      anthropometric measures. Both DDS and FVS could be used in dietary assessment
      studies on children. This is the first research quantified the difference in
      dietary diversity and micronutrient status of infants in rural and urban areas of
      China. Our work can potentially serve as a guide to infant feeding
      recommendations.

PMID- 30181994
TI  - Epidemiology of Fascioliasis in Kermanshah Province, Western Iran.
AB  - Background: We aimed to determine the prevalence of fasciolosis in the definitive
      hosts (human and livestock) and intermediate (Lymnaea snails) hosts in Kermanshah
      Province, western Iran from 2014-2016. Methods: The study on animals was
      descriptive and retrospective one. All daily records of animals slaughtered in
      the abattoirs were analyzed. For the study of human fascioliasis, 975 serum
      samples were collected from different parts of Kermanshah Province and analyzed
      using ELISA based on excretory-secretory antigens. Moreover, 4400 Lymnaea snails
      were collected from 25 habitats. The snails were identified and examined for
      presence of cercariae by shedding method. Results: Fasciolosis was diagnosed in
      1.7% of slaughtered animals, which was significantly greater than the other
      species (P<0.005). There was significant difference (P<0.001) between the
      prevalence of fasciolosis and seasonal pattern. As for human cases, five cases
      (0.5%) were positive for fascioliasis. Regarding the seropositivity to
      fasciolosis, no significant differences were found for age groups, sex, level of
      education and occupation. No Fasciola infection was seen in snails of the family
      Lymnaeidae. Conclusion: The prevalence of Fasciola parasite was lower compared to
      other provinces. This is probably due to sequential decline in rainfall and hot
      climate that makes conditions difficult for the snail intermediate host snails
      and the larval stages of fasciolid trematodes. The habitual food of people is
      another important point.

PMID- 30181995
TI  - Haplotype Analysis of PPARgamma Gene Polymorphisms and the Lipoprotein (a) Level.
AB  - Background: Lipoprotein (a) [Lp(a)], as an independent risk factor for
      cardiovascular disease, is more likely to be genetically determined according to
      the increasing evidence of epidemiologic and clinical studies in recent years.
      Peroxisome proliferator-activated receptor (PPAR) gamma, the ligand-activated
      transcription factors, was considered as an indispensable role in the process of
      lipid metabolism. This study was designed to explore the associations of three
      single-nucleotide polymorphisms (SNPs) and the haplotypes of the peroxisome
      proliferator-activated receptor (PPAR)gamma gene with the level of Lp(a).
      Methods: Participants were recruited under the framework of the PMMJS (The
      Prevention of Metabolic Syndrome (MS) and Multi-metabolic Disorders in Jiangsu
      Province of China Study) from Apr 1999 to Jun 2004. Overall, 644 subjects were
      randomly selected and 3 SNPs of PPARgamma gene (rs10865710, rs1805192, rs4684847)
      were genotyped. Results: After adjusting for age, sex, cigarette smoking, alcohol
      drinking, waist circumference and body mass index, rs4684847 was significantly
      associated with Lp (a). The presence of the rs4684847 T allele (CT+TT) have a
      lower level of Lp (a) than the allele (CC) in the dominant model, mean difference
      was -27.30 (95% CI: -52.88~-1.73) mg/L, P<0.05. G-P-T and G-A-T haplotype were
      associated with lower levels of Lp (a) (P=0.0041 and <0.0001), mean difference
      was 49.79 (95% CI: -97.52~-2.06) mg/L and 17.75 (95% CI: -25.75~-9.75) mg/L.
      Conclusion: PPAR gamma polymorphisms (rs10865710, rs1805192, rs4684847) and
      haplotypes may be the genetic risk factors for Lp (a) level.

PMID- 30181996
TI  - Risk Factors Associated with Survival of Pulmonary Tuberculosis.
AB  - Background: We conducted this study among adults with pulmonary tuberculosis (TB)
      who received treatment, in order to determine the risk factors associated with
      survival of during treatments. Methods: A retrospective cohort study was
      conducted from 2005-2015 with newly registered TB patients in the Hospital of
      Masih Daneshvari Doctor, Tehran, Iran. Overall, 5313 patients met our study's
      cohort definition, but the analysis was performed on 2299 patients (43.2%) who
      had a correct address and they could be traced-out by the Medical - registry.
      Time in days was used in survival model and patients who were still alive (until
      last follow-up date) considered as censored. To study the effect of risk factors
      on patients' survival, the generalized gamma regression model was used. Results:
      Based on the results of univariate analysis, gender (RR=2 (95% CI: 1.1-3.7), high
      school education (Relative Risk: RR=0.3 (95% CI: 0.2-0.7), higher education
      (RR=0.3 (95% CI: 0.1-0.9), smoker (RR=2.5 (95% CI: 1.4-4.2), drug user (RR=2.4
      (95% CI: 1.4-4), TB contact (RR=0.5 (95% CI: 0.3-0.8) and HIV positive (RR=4 (95%
      CI: 1.7-9.2) affected patients' survival. Moreover, the results of multivariate
      analysis showed that, gender (RR=5.5 (95% CI: 2.2-13.5), age (RR=1.1 (95% CI: 1
      1.1), adverse drug effect (RR=2.5 (95% CI: 1.2-5.4), smoker (RR=3.3 (95% CI: 1.2
      9.4), TB contact (RR=0.2 (95% CI: 0.1-0.5), diabetic mellitus (RR=3 (95% CI: 1
      8.3), HIV positive (RR=26 (95% CI: 4.6-145.9) and comorbidities (RR=4.9 (95% CI:
      2-11.6) were identified as factors affecting patients' survival. Conclusion: Our
      data indicated associated risk factors in TB mortality and could suggest way to
      progressing national tuberculosis program (NTP) for predicating and plan for
      effective interventional strategies.

PMID- 30181997
TI  - Correlations of Post-stroke Depression with Inflammatory Response Factors.
AB  - Background: We aimed to investigate the correlations of the inflammatory response
      factors, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), high
      sensitivity C-reactive protein (CRP), with patients with post-stroke depression
      (PSD), so as to provide a basis for the treatment and prevention of PSD for
      patients. Methods: The clinical laboratory data of 60 patients with PSD in The
      Second Affiliated Hospital of Qiqihar Medical University, Qiqihar, China from
      July 2016 to July 2017 and those of another 60 stroke patients without PSD
      admitted in the same period were analyzed retrospectively. The expression levels
      of inflammatory response factors in the two groups of patients and in PSD
      patients with different levels of depression were compared and analyzed via
      statistical methods. Multiple Logistic regression analysis was used to determine
      whether inflammatory response factors were independent risk factors for PSD
      patients. Results: The expression levels of IL-6, TNF-alpha and CRP in patients
      with PSD were significantly increased compared with those in patients without
      PSD, and the differences were statistically significant (t=6.429, t=6.355,
      t=5.792, P<0.001). The levels of IL-6, TNF-alpha and CRP had statistically
      significant differences between any two groups of mild, moderate and severe PSD
      patients (P<0.05). Results of multiple Logistic regression analysis revealed that
      the odds ratio (OR) values of inflammatory factors (IL-6, TNF-alpha and CRP) were
      1.160, 1.099 and 1.248, respectively, and the corresponding p values were 0.020,
      0.039 and 0.007 in patients of observation group, indicating the above three
      inflammatory response factors were independent risk factors for PSD. Conclusion:
      The clinic control on the expression levels of inflammatory response factors (IL
      6, TNF-alpha and CRP) are extremely important for the treatment and prevention of
      PSD.

PMID- 30181998
TI  - Isolation and Characterization of Clinical Triazole Resistance Aspergillus
      fumigatus in Iran.
AB  - Background: Aspergillus fumigatus is a major cause of allergic syndromes,
      aspergilloma and life-threatening invasive infections in immunocompromised hosts.
      To date, a wide range of mutations in A. fumigatushave been described conferring
      azole-resistance, which commonly involves modifications in the cyp51A-gene
      (substitutions at codons G54, G138, P216, F219, M220, G448 and specifically codon
      L98 in combination with a 34-bp tandem repeat in the promoter region of the
      gene), the target for azole antifungals. We investigated the prevalence of azole
      resistance in clinical A. fumigatus isolates obtained from patients in Iran
      during 2010 to 2014. Methods: Overall, 172 clinical A. fumigatus isolates
      obtained from patients with underlying disease including transplantation,
      granulocytopenia, chronic liver disease, chronic obstructive pulmonary disease
      (COPD) and allergic bronchopulmonary aspergillosis (ABPA). Samples were collected
      between Jan 2009 and Nov 2014 from five provinces of Iran (Tehran, Shiraz,
      Isfahan, Khorasan razavi and East Azerbaijan). Antifungal susceptibility test was
      determined according to EUCAST reference method for itraconazole (ITC),
      voriconazole (VRC) and posaconazole (POS). All isolates were confirmed by
      amplification of the partial tubulin gene. Results: Of 172 A. fumigatus isolates
      tested, six isolates (3.5%) had high MIC values of ITC (>16 mg/L) and VRC (>=4
      mg/L). All six isolates showed a multi-resistant phenotype with high MICs of ITC
      and VRC. Conclusion: We determined in-vitro susceptibility a profile of 172
      clinically isolates of A. fumigatus against triazole in Iran. Azole-resistance is
      an emerging problem in A. fumigatus and international surveillance is warranted.

PMID- 30181999
TI  - The Effects of Pulmonary Physical Therapy on the Patients with Respiratory
      Failure.
AB  - Background: We aimed to investigate the application effects of pulmonary physical
      therapy on the patients with respiratory failure. Methods: Overall, 132 patients
      with respiratory failure admitted into the Affiliated Hospital of Medical Collage
      of Ningbo University from 2013-2017 were enrolled and divided into control group
      (n=66) and observation group (n=66). Patients in the two groups received
      conventional physical therapy but those in observation group received pulmonary
      physical therapy additionally. The ventilation and air-exchanging functions,
      scores of acute physiology and chronic health evaluation II (APACHE II) and
      occurrence of complications in patients in the two groups were compared. Results:
      PaO2, PaCO2, PaO2/FiO2 and estimated FEV2% were greatly improved in patients in
      the two groups after treatment and those in patients in observation group were
      better than those in patients in control group; the differences were
      statistically significant (P=0.014). There were no statistically significant
      differences in the scores of APACHE II in patients in the two groups before
      treatment and at 2 days and 3 days after treatment. Scores of APACHE II of
      patients in observation group were obviously lower than those of other group at 4
      days and 7 days after treatment and the differences were statistically
      significant (P=0.015, 0.029). The total incidence rates of complications in
      patients in observation group and control group were 7.57% and 39.39%,
      respectively, and the difference was statistically significant (P=0.021).
      Conclusion: The treatment of respiratory failure patients with pulmonary physical
      therapy can greatly improve the ventilation and air-exchanging functions, avoid
      the occurrence of complications and improve the health condition.

PMID- 30182000
TI  - Process and Results of Implementing Disease Management Program in Patients with
      First-time Ischemic Stroke.
AB  - Background: This study aimed to examine the effect of disease management program
      (DMP) on the patients with first-time ischemic stroke (IS). Methods: A DMP with 4
      parts of performance indicators (PIs, including outpatient, emergency department,
      inpatient and follow-up treatment) was implemented in patients with stroke in 2
      hospitals (Hospital T and R) in Shanghai China from 2007-2010. The effect of DMP
      on the outcome of IS patients was analyzed according to the criteria of the
      National Institute of Health Stroke Scale (NIHSS). Furthermore, the total
      effective rate of DMP, average length of stay, hospitalization cost, and cost
      effectiveness ratio (CER) between DMP and non-DMP patients were calculated,
      followed by the cost-effectiveness analysis. Results: The total effective rate of
      DMP (T: 69.9%; R: 76.6%) was significantly (P<0.05) higher than that of non-DMP
      (T: 60.8%; R: 62.7%) group in the same hospital. In addition, a significant
      (P<0.05) difference in effective rate was observed between DMP and non-DMP at the
      NIHSS score >= 7. Furthermore, the average length of stay and hospitalization
      cost of the patients in DMP group were significantly (P<0.05) lower than those in
      non-DMP group. A superior CER was also found in DMP group than non-DMP group.
      Conclusion: The implementation of DMP for IS can effectively improve the
      treatment outcome and reduce the average length of stay and hospitalization cost.

PMID- 30182001
TI  - Epidemiology and Serum Metabolic Characteristics of Acute Myocardial Infarction
      Patients in Chest Pain Centers.
AB  - Background: We aimed to find a potential earlier diagnostic strategy for acute
      myocardial infarction (AMI) by investigating the epidemiology and serum metabolic
      characteristics of AMI patients in comparison with those of chest pain controls
      (CPCS). Methods: We conducted this prospective, non-randomized, observational
      study of patients with acute chest pain symptoms presenting to the Emergency
      Rooms (ER) in The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning,
      Guangxi Province, China from January 2015 to July 2016. We included a cohort of
      45 patients with AMI together with 45 age- and sex-matched CPCS. The epidemiology
      of AMI was collected, and the phenotypic characteristics of the serum metabolite
      composition of AMI patients were determined using a combination of 1H nuclear
      magnetic resonance (NMR)-based metabolomics and clinical assays. Results: The
      epidemiology showed that elderly AMI patients with chest pain syndrome presenting
      to ER have little awareness of their physical condition and compliance with
      medication. Significant serum metabolic differences observed between AMI patients
      and CPCS were highlighted by system differentiations in multiple metabolic
      pathways including anaerobic glycolysis, gluconeogenesis, tricarboxylic acid
      cycle (TCA cycle), protein biosynthesis, lipoprotein changes, choline and fatty
      acid metabolisms and intestinal microbial metabolism. Conclusion: The
      epidemiology and serum metabolic phenotypes observed here demonstrated that
      integration of metabolomics with other techniques could be useful for better
      understanding the biochemistry of AMI and for potential AMI molecular diagnosis.
      We should improve the general public's awareness of AMI, including early
      symptoms, risk factors, emergency responses, and treatments for related
      comorbidities.

PMID- 30182002
TI  - Effect of Oral Herbal Medicament on Scalp Seborrhea and Gastrointestinal Symptoms
      in a Male Patient: A Case Report.
AB  - A 32-yr-old man with a 10-yr history of scalp seborrhea referred to Skin and Stem
      Cell Research Center, Tehran, Iran, in 2015. He suffered from scalp seborrhea.
      Concurrent gastrointestinal symptoms and the changes in the clinical symptoms
      after consumption of the polyherbal traditional drug called Triphala are
      discussed. The scalp sebum was measured with a Sebumeter SM815. Gastrointestinal
      symptoms were followed using a valid questionnaire. After two months of
      treatment, scalp sebum secretion had decreased substantially. The patient also
      experienced remarkable improvement in gastrointestinal symptoms. Considering the
      positive effect of this known and safe polyherbal drug on skin sebum, it is an
      appropriate option for detailed large-scale clinical trials.

PMID- 30182003
TI  - Idiopathic Chylous Ascites in Pregnancy: A Case Report.
AB  - Idiopathic chylous ascites in pregnancy is extremely rare. Here, we report a 24
      yr-old patient with idiopathic chylous ascites in pregnancy. The patient was
      hospitalized in Xiamen Maternity and Child Health Care Hospital, Xiamen China in
      2014 due to G1P0 intrauterine pregnancy 39+2 week, LOA, and time of labor. The
      patient gave birth to a live baby boy (3.6 kg) by spontaneous vaginal delivery,
      with complete delivery of placenta. Three hours after delivery, the patient
      reported abdominal distension and pain, as well as asthma. Later, milky white
      liquid was drawn from left lower abdomen by puncture. Exploratory laparotomy was
      performed, and 800 ml milky white liquid was drawn from the abdominal cavity.
      Subsequently, drainage tube was placed in the abdominal cavity, and the abdomen
      was closed. After the surgery, the patient was given low-fat diet, supplemented
      with parenteral nutrition support and intravenous injection of antibiotics.
      Extubation was performed on day 3. On day 7 after surgery, the mother and baby
      left the hospital without any health problems. No abnormality was observed during
      six months of follow-ups. Idiopathic chylous ascites in pregnancy may be related
      to congenital lymphatic system dysplasia, and directly caused by chylous flow
      from ducts into abdominal cavity induced by progesterone during pregnancy or
      pressure from enlarged uterus during late pregnancy. After pregnancy, the disease
      is cured by the release of disease cause and the reduction of thoracic duct
      pressure.

PMID- 30182004
TI  - Resistance Training Data Analysis on Blood and Personal Profiles for Customized
      Healthcare.

PMID- 30182005
TI  - Strict Product Liability of Medical Employees for Damage Caused by the Use of
      Medical Means with Deficiency in the USA Law.

PMID- 30182006
TI  - Exercise Rehabilitative Approach to Functional Improvement in Adult Idiopathic
      Scoliosis: A Functional Movement Screen-based Program.

PMID- 30182007
TI  - Effects of Food Consumption on Self-rated Health: Evidence from Korean
      Adolescents.

PMID- 30182008
TI  - Effect of Competitive and Non-competitive Exercise on Serotonin Levels in
      Adolescents with Various Levels of Internet Gaming Addiction.

PMID- 30182009
TI  - Have We Forgotten the Threat Posed by HIV?

PMID- 30182010
TI  - Medical Errors, Regrettable Mistakes in Public Health.

PMID- 30182011
TI  - Traditional Milk Marketing Chain: One of the Leading Causes of Fatal Diseases in
      Pakistan.

PMID- 30182012
TI  - Auricular Acupuncture for Craving in a Single-subject Case Study of Woman with
      Fibromyalgia and Chronic Ecstasy Use.

PMID- 30182013
TI  - Complications in Diagnosis of Susceptible Cases of Fragile X Syndrome.

PMID- 30182014
TI  - Universal Health Coverage (UHC) in Iran.

PMID- 30182015
TI  - The Relationship between Peritoneum and Body Organs in Persian Medicine.

PMID- 30182016
TI  - What Caused Seriously Shortage of Chinese Nurses?

PMID- 30182017
TI  - Colonoscopy education for surgical residents in Korea: a national survey of
      Korean Surgical Skill Study Group.
AB  - Purpose: A standardized colonoscopy training program surgical residents is still
      unestablished. The aim of this study was to assess the current status of
      colonoscopy training for surgical residents and collect the opinions on the
      direction for future colonoscopy education. Methods: A questionnaire survey
      containing 24 items was conducted by sending an email to 310 colorectal surgeons
      in 84 training hospitals across the country. Results: One hundred fifteen staff
      surgeons (115 of 310, 37%) of 84 institutions returned fully completed
      questionnaires. Most surgeons were working at tertiary hospitals with more than 5
      years of clinical experience. About half of the responding surgeons answered that
      they perform colonoscopy in clinical practice and the main purpose of colonoscopy
      was follow-up after colorectal resection. Only 9 of 84 hospitals (10.7%) had a
      regular program on colonoscopy training for surgical residents. Most of
      colonoscopy education was conducted irregularly in a form of staff lecture,
      conferences or hands-on workshops. According to the future directions, 72 of 115
      surgeons (62.6%) answered judging competency in colonoscopy should be needed for
      professional qualification of the surgeon. About 50 cases of colonoscopy seem
      appropriate during the 4-year-training of surgical residency, especially during
      the third- and fourth-year. Conclusion: This survey shows colonoscopy education
      for surgical residents is still insufficient in Korea and that most surgeons feel
      that regular colonoscopy training is needed during the surgical residency period.
      There needs to be efforts to standardize the education program as well as various
      institutional and academic societal supports to achieve this goal.

PMID- 30182018
TI  - Wound healing and postsurgical complications in breast cancer surgery: a
      comparison between PEAK PlasmaBlade and conventional electrosurgery - a
      preliminary report of a case series.
AB  - Purpose: PEAK PlasmaBlade is a recent and distinctive type of electrosurgical
      device. Previous studies have already documented some meaningful advantages of
      this device over conventional electrosurgery. This study compared the use of PEAK
      PlasmaBlade to standard electrosurgery in mastectomy and breast conservative
      surgery. The purpose was to test the impact of PEAK PlasmaBlade on the wound
      healing process and on postsurgical complications in breast cancer surgery.
      Methods: Sixty patients undergoing breast cancer surgery were enrolled. The PEAK
      PlasmaBlade was used for 20 of those. A standard electrosurgical device was used
      for the other 40 patients. The 2 groups were homogenous in age, body mass index,
      comorbidities and type of surgery. We recorded wound complications, serum
      drainage amount and duration of stay, blood loss, time of surgery, length of
      hospital stay, and total number of medications required. Results: The 2 groups
      were not significantly different in terms of patient characteristics. A
      statistically significant reduction in incidence of seroma was observed in the
      PEAK group: only 10% versus 37.5% of the patients in the conventional
      electrosurgery group developed this complication (Fisher exact test, P = 0.034).
      Conclusion: Seroma is the most important wound complication in breast surgery.
      The research of new instruments that might reduce its incidence is desirable. In
      order to validate or deny the results of this study, it is necessary to enroll
      more subjects and to consider the impact of this device on axillary lymph node
      dissection.

PMID- 30182019
TI  - Postcholecystectomy syndrome: symptom clusters after laparoscopic
      cholecystectomy.
AB  - Purpose: Postcholecystectomy syndrome (PCS) is characterized by abdominal
      symptoms following gallbladder removal. However, there is no consensus for the
      definition or treatment for PCS. The purpose of this study was to define PCS
      among various symptoms after laparoscopic cholecystectomy, and to identify risk
      factors affecting PCS. Methods: This study was conducted at Dongguk University
      Ilsan Hospital and Chung-Ang University Hospital (2012-2013). Outcomes were
      assessed using European Organization for Research and Treatment of Cancer QLQ-C30
      questionnaire. Symptom cluster for determining PCS was made by factor analysis.
      Cluster analysis evaluating risk factors of PCS was made by Ward methods and
      Dentogram. Results: Factor analysis revealed three distinct symptom clusters,
      those are 'insomnia and financial difficulties (eigenvalue, 1.707; Cronbach
      alpha, 0.190),' 'appetite loss and constipation (eigenvalue, 1.413; Cronbach
      alpha, 0.480),' and 'right upper quadrant (RUQ) pain and diarrhea (eigenvalue,
      1.245; Cronbach alpha, 0.315).' Among these symptom clusters, the cluster of 'RUQ
      pain and diarrhea' was determined as PCS. However, we could not find any risk
      factors between high symptomatic group and low symptomatic group. Conclusion: PCS
      could consist of RUQ pain and diarrhea. Well-designed prospective trials are
      needed to determine risk factors of PCS.

PMID- 30182020
TI  - Clinical implication of spontaneous gastrointestinal perforation in pediatric
      patients: its difference according to age group.
AB  - Purpose: Spontaneous gastrointestinal perforations (SGIPs; not associated with
      injury or disease) occur rarely in pediatric patients. This study aimed to define
      age-specific features associated with SGIPs in pediatric patients. Methods:
      Retrospectively reviewed the clinical data of children (before adolescence) who
      received surgery due to a SGIP at a single institution. Thirty-nine patients were
      enrolled. Characteristics were compared between the 2 age groups: neonates (group
      A) and beyond neonates (group B). Results: Group A included 24 patients (61.5%)
      an group B included 15 patients (38.5%). Thirteen perforations occurred in the
      stomach (33.3%), 12 in the small intestine (30.8%), and 14 in the large intestine
      (35.9%). A significantly higher proportion of perforations occurred in the
      stomach and small intestine in group A, while more perforations occurred in the
      large intestine in group B (P = 0.01). Several associated conditions during the
      preoperative period were identified in both groups. The overall mortality rate
      was 15.4% (6 of 39). Mortality was relatively high in group A (5 of 24, 20.8%)
      and for perforations of stomach (3 of 13, 23.1%) and small intestine (3 of 12,
      25.0%); however, there were no significant differences with regard to age or
      perforation site (P = 0.244, P = 0.122, respectively). Conclusion: SGIPs in
      pediatric patients had diverse clinical features and different perforation
      patterns according to age group. However, no significant group differences in
      mortality were found. Thus, favorable results regardless of age can be expected
      with prompt recognition, medical resuscitation, and adequate surgical management.

PMID- 30182021
TI  - Use of direct antiviral agents in liver transplant recipients with hepatitis C
      virus in Korea: 2-center experience.
AB  - Purpose: The proportion of liver recipients with HCV is gradually increasing in
      Korea. Limited data are available regarding the efficacy of direct antiviral
      agents (DAAs) in liver transplant recipients in Asia. We aimed to assess the
      efficacy and safety of DAAs in HCV-infected liver recipients in Korea. Methods:
      Forty HCV-infected patients from 2 centers received DAAs in the pretransplant or
      posttransplant period between May 2015 and November 2016. Results: DAA was
      administered in the pretransplant period in 6 patients and the posttransplant
      period in 34 patients. Dalastavir and asunaprevir (n = 2) and
      sofosbuvir/ledipasvir and ribvarin (n = 4) were used in the pretransplant period.
      HCV RNA was not detected before liver transplantation in all patients. Sustained
      virological response (SVR) at 12 and 24 weeks after liver transplantation was
      100%. In the posttransplant period, 33 of 34 patients received sofosfovir-based
      therapy. SVR at 12 weeks in those patients was 94%. Recurrent virologic relapse
      developed in 2 patients because of HCC recurrence or treatment failure. Adverse
      events included anemia (n = 2) and abdominal discomfort (n = 1). Conclusion: DAAs
      are an effective and well-tolerated treatment for HCV-infected recipients in
      Korea.

PMID- 30182022
TI  - Continuing five or more locoregional therapies before living donor salvage liver
      transplantation for hepatocellular carcinoma is related to poor recurrence-free
      survival.
AB  - Purpose: This study was designed to analyze factors related to the success of
      salvage liver transplantation (SLT) in hepatocellular carcinoma (HCC). While
      liver resection (LR) is considered the best locoregional therapy in HCC, there is
      a high recurrence rate. SLT may be the best treatment option when feasible.
      Methods: Patients who underwent living donor SLT for recurrent HCC after LR from
      November 1996 to May 2017 were included. Patient demographic data, clinical and
      pathologic characteristics, operative data, hospital course, and follow-up data
      regarding initial LR, locoregional therapy after recurrence and SLT were
      reviewed. Prognostic factors for recurrence were analyzed using Cox proportional
      hazard ratio. Results: Eighty-five of 123 SLT patients were included. Patients
      who had five or more locoregional therapies prior to SLT (hazard ratio [HR],
      3.74; 95% confidence interval [CI], 1.45-9.64, P = 0.006), hepatitis B (HR, 9.20;
      95% CI, 1.13-74.89; P = 0.04), outside Milan criteria at the time of SLT (HR,
      2.66, 95% CI, 1.26-5.63; P = 0.011) and an alpha-fetoprotein level above 1,000
      ng/mL at the time of recurrence after initial LR (HR, 6.48; 95% CI, 1.83-22.92; P
      = 0.004) and at the time of transplantation (HR, 3.43; 95% CI, 1.26-5.63; P =
      0.011) were related to significant risk of recurrence. Conclusion: Continuing
      five or more locoregional therapies for recurrent HCC after LR is related to poor
      recurrence-free survival after SLT.

PMID- 30182023
TI  - Protective effect of Korean red ginseng on oxaliplatin-mediated splenomegaly in
      colon cancer.
AB  - Purpose: This study investigated how adding Korean red ginseng extract (KRG) to
      folinic acid, fluorouracil and oxaliplatin (FOLFOX) chemotherapy affected the
      rate of splenomegaly in colon cancer. Methods: This retrospective study analyzed
      42 patients who were randomly assigned to receive a FOLFOX regimen with or
      without KRG. Spleen volume change was assessed by computed tomography scans
      measured before surgery (presurgery volume) and 3 weeks after cessation of the
      12th cycle of FOLFOX (postchemotherapy volume). Results: All patients showed
      increased spleen volume. No difference was observed in median presurgery and
      postchemotherapy volume between the KRG and control groups. However, a ratio
      defined as postchemotherapy volume divided by presurgery volume was significantly
      lower in the KRG group than the control group (median, 1.38 [range, 1.0-2.8] in
      KRG group vs. median, 1.89 [range, 1.1-3.0] in control group, P = 0.028). When
      splenomegaly was defined as a >61% increase in spleen volume, the rate of
      splenomegaly was significantly lower in the KRG group than the control group
      (28.6% vs. 61.9%, P = 0.03). KRG consumption was inversely associated with
      developing splenomegaly in multivariate analysis. Conclusion: Adding KRG during
      FOLFOX chemotherapy for colon cancer might protect against oxaliplatin-induced
      splenomegaly. The protective effect of Korean red ginseng should be investigated
      with further research.

PMID- 30182024
TI  - Pancreatic Cystic Neoplasms: Different Types, Different Management, New
      Guidelines.
AB  - Pancreatic cystic neoplasms (PCN) include different types of cysts with various
      biological behavior. The most prevalent PCN are intraductal papillary mucinous
      neoplasm (IPMN), mucinous cystic neoplasm (MCN), and serous cystic neoplasm
      (SCN). Management of PCN should focus on the prevention of malignant progression,
      while avoiding unnecessary morbidity of surgery. This requires specialized
      centers with dedicated multidisciplinary PCN teams. The malignant potential of
      PCN varies enormously between the various types of PCN. A combination of computed
      tomography, magnetic resonance imaging/magnetic resonance
      cholangiopancreatography, and endoscopic ultrasound with or without fine needle
      aspiration is typically needed before a reliable diagnosis can be made. Several
      guidelines discuss the management of PCN; however, most of these are non-evidence
      based without clear consensus on the optimal treatment and follow-up strategy.
      The 2018 European guidelines on PCN are the first evidence-based guidelines to
      include IPMN, MCN, SCN, and all other PCN. This guideline advises a more
      conservative approach to side-branch IPMN and MCN smaller than 40 mm and more
      often a surgical approach in IPMN with a main duct dilatation beyond 5 mm. The
      goal of this review is to summarize the different types and management of the
      most common PCN based on the current literature and guidelines.

PMID- 30182025
TI  - Surgery of Cystic Tumors of the Pancreas - Why, When, and How?
AB  - The management of cystic pancreatic neoplasms has increasingly gained clinical
      attention due to their frequent incidental detection by cross-sectional imaging
      and their potential for progression to pancreatic cancer. Surgical resection is
      warranted for all mucinous cystic neoplasms, solid pseudopapillary neoplasms, and
      main-duct intraductal papillary mucinous neoplasms since these lesions harbor a
      major risk for malignant transformation. For branch-duct IPMN (BD-IPMN), the risk
      for malignancy is considerably lower so that some lesions may be safely followed
      while others require surgical resection. The clinical challenge lies in making
      the correct preoperative diagnosis and estimation of the risk of malignancy in BD
      IPMN. Therefore, the existing evidence and current guidelines on the management
      of cystic lesions of the pancreas are summarized and controversially discussed
      from a surgical point of view.

PMID- 30182026
TI  - Does Remnant Preservation Influence Tibial Tunnel Enlargement or Graft-to-Bone
      Integration After Double-Bundle Anterior Cruciate Ligament Reconstruction Using
      Hamstring Autografts and Suspensory Fixation? A Computed Tomography and Magnetic
      Resonance Imaging Evaluation.
AB  - Background: Remnant-preserving anterior cruciate ligament (ACL) reconstruction
      was introduced to improve clinical outcomes and biological healing. However, the
      influences of remnant preservation on tibial tunnel position and enlargement are
      still uncertain. Purpose: To evaluate whether remnant-preserving ACL
      reconstruction influences tibial tunnel position or enlargement and to examine
      the relationship between tunnel enlargement and graft-to-bone integration in the
      tibial tunnel. Study Design: Cohort study; Level of evidence, 2. Methods: A total
      of 91 knees with double-bundle ACL reconstructions were enrolled in this study.
      ACL reconstruction was performed without a remnant (<25% of the intra-articular
      portion of the graft) in 44 knees (nonremnant [NR] group) and with remnant
      preservation in the remaining 47 knees (remnant-preserving [RP] group). Tibial
      tunnel position and enlargement were assessed using computed tomography (CT).
      Comparisons between groups were performed. Furthermore, graft-to-bone integration
      in the tibial tunnel was evaluated using magnetic resonance imaging, and the
      relationship between tunnel enlargement and graft-to-bone integration at 1 year
      after ACL reconstruction was assessed. Results: A total of 48 knees (25 in NR
      group, 23 in RP group) were included; 19 and 24 knees in the NR and RP groups
      were excluded, respectively, because of graft reruptures and a lack of CT scans.
      There were no significant between-group differences in tibial tunnel position (P
      > .05). The degree of posterolateral tunnel enlargement in the axial plane was
      significantly higher in the RP group than that in the NR group (P = .007) 1 year
      after ACL reconstruction. The degree of anteromedial tunnel enlargement on axial
      CT was significantly smaller in knees with graft-to-bone integration than in
      those without integration (P = .002) 1 year after ACL reconstruction. Conclusion:
      ACL reconstruction with remnant preservation did not influence tibial tunnel
      position and did not decrease the degree or incidence of tibial tunnel
      enlargement. At 1 year postoperatively, tunnel enlargement did not affect graft
      to-bone integration in the posterolateral tunnel, but graft-to-bone integration
      was delayed in the anteromedial tunnel.

PMID- 30182027
TI  - Jones Fractures Identified at the National Football League Scouting Combine:
      Assessment of Prognostic Factors, Computed Tomography Findings, and Initial
      Career Performance.
AB  - Background: Jones fractures result in subsequent dysfunction and remain an issue
      for athletes. Purpose: To (1) describe the epidemiology, treatment, and impact of
      Jones fractures identified at the National Football League (NFL) Scouting Combine
      on players' early careers and (2) establish the value of computed tomography (CT)
      to determine bony healing after a fracture in prospective players. Study Design:
      Cohort study; Level of evidence, 3. Methods: All players who attended the combine
      between 2009 and 2015 were retrospectively reviewed to identify their history of
      Jones fractures. The playing position, treatment method, and number of missed
      collegiate games were recorded. The mean overall draft pick number, number of
      games started and played, snap percentage, and position-specific performance
      scores (fantasy score) over the first 2 years in the NFL were compared between
      players with fractures and controls. An imaging classification system was applied
      based on grading of each quadrant of the fifth metatarsal (plantar, dorsal,
      medial, lateral), with a score of 0 for not healed or 1 for healed. Results:
      Overall, the number of Jones fractures identified was 72 in 2285 athletes (3.2%),
      with all treated via intramedullary screw fixation. The mean overall draft pick
      number for players with fractures was 111.2 +/- 67.9 compared with 99.0 +/- 65.9
      for controls (P = .12). Performance scores for players with fractures were lower
      than those for controls across all positions, with a significant difference in
      running backs (2.6 vs 4.0, respectively; P < .001) and defensive linemen (1.4 vs
      2.3, respectively; P = .02). The mean CT score was 2.5 +/- 1.3. Of the 32
      athletes who underwent imaging, 16 Jones fractures (50.0%) were healed or nearly
      healed, 12 (37.5%) were partially healed, and 4 (12.5%) showed little or no
      healing. The plantar cortex demonstrated the least healing (18/32; 56.3%),
      followed by the lateral cortex (15/32; 46.9%). Players with a mean score <1 were
      found to have fewer games started (2.7 +/- 2.5) than those with 1 to 3 cortices
      healed (17.4 +/- 10.4) or all cortices healed (8.7 +/- 11.2). Conclusion: Based
      on CT, 50% of all players with a previous Jones fracture demonstrated incomplete
      healing. Moreover, position-specific performance scores over the first 2 years of
      a player's career were lower across all positions for those with fractures
      compared with controls. Players with CT scores <1 were found to start fewer games
      and were drafted later than controls.

PMID- 30182028
TI  - Short-term Outcomes of Arthroscopic Debridement and Selected Acromioplasty of
      Bursal- vs Articular-Sided Partial-Thickness Rotator Cuff Tears of Less Than 50.
AB  - Background: While it is believed that good results can be achieved by
      arthroscopic debridement of partial-thickness tears (PTTs) of <50% tendon
      thickness, few studies have directly compared the treatment of articular- versus
      bursal-sided PTTs of <50%. Purpose: To compare the postoperative outcomes of
      patients with articular- versus bursal-sided PTTs of <50% tendon thickness that
      were treated with arthroscopic debridement and selective acromioplasty (for type
      II or III acromions). Study Design: Cohort study; Level of evidence, 3. Methods:
      An analysis was performed with data from 76 consecutive patients diagnosed with a
      PTT <50% tendon width (Ellman grade II) who had undergone arthroscopic
      debridement and selective acromioplasty (for type II or III acromions). Outcome
      measures included the short version of the Western Ontario Rotator Cuff index,
      the American Shoulder and Elbow Surgeons score, and the relative Constant-Murley
      score, as well as strength of the affected shoulder. A statistical paired t test
      (preoperative vs 2 years postoperative) and an independent t test were utilized
      to compare outcomes between patients with bursal- and articular-sided tears.
      Results: Between 2001 and 2010, there were 40 (53%) articular- and 36 (47%)
      bursal-sided tears treated with debridement and selective acromioplasty. The mean
      patient age was 55 years (range, 36-77 years) for the bursal group and 56 years
      (range, 33-81 years) for the articular group. The mean follow-up was 24 months
      (range, 22-26 months). Both groups showed significant improvement in the short
      version of the Western Ontario Rotator Cuff index, American Shoulder and Elbow
      Surgeons score, and relative Constant-Murley score 2 years after surgery (P <
      .0001) as well as in strength (P < .0001 for bursal tears, P = .006 for articular
      tears). There was no statistically significant difference between groups in any
      of the postoperative outcome measures at 2 years. Conclusion: The results of this
      study demonstrate that good outcomes can be achieved with arthroscopic
      debridement and selective acromioplasty among patients with articular- or bursal
      sided PTT of <50% tendon thickness. No difference was observed between groups at
      2-year follow-up.

PMID- 30182029
TI  - Pathogenic Factors Associated With Osgood-Schlatter Disease in Adolescent Male
      Soccer Players: A Prospective Cohort Study.
AB  - Background: A previous cross-sectional study reported that pathogenic factors
      associated with Osgood-Schlatter disease (OSD) in adolescent athletes include
      increased quadriceps muscle tightness, lower leg malalignment, and development of
      apophysitis in the tibial tuberosity. Purpose: To confirm these pathogenic
      factors associated with OSD in a longitudinal study with regard to physical
      function and performance. Study Design: Cohort study; Level of evidence, 2.
      Methods: In this study, 37 boys (mean age, 10.2 +/- 0.4 years) were recruited
      from 2 soccer teams at an elementary school. This cohort study was conducted over
      an observation period of 1 year, with measurements recorded at baseline, followed
      by screening for OSD every 6 months. Variables evaluated at baseline included
      physical function (morphometry, joint flexibility, and lower extremity
      alignment), presence of Sever disease, and kicking motion. Results: Pathogenic
      factors associated with OSD in the support leg of adolescent male soccer players
      included height, weight, body mass index, quadriceps femoris muscle tightness in
      the kicking and support legs, and gastrocnemius muscle tightness, soleus muscle
      tightness, and medial longitudinal arch in the support leg. Additional factors
      included a diagnosis of Sever disease and distance from the lateral malleolus of
      the support leg's fibula to the center of gravity during kicking. Conclusion: The
      onset of OSD was found to be affected by many factors, including developmental
      stage, physical attributes, and pre-existing apophysitis. In particular, a
      diagnosis of Sever disease and backward shifting of the center of gravity during
      kicking increased the risk of the subsequent onset of OSD, suggesting that these
      factors are very important as a possible focus for interventions.

PMID- 30182030
TI  - HIV Testing After a First Positive Rapid Diagnostic Test: A Role for Nucleic Acid
      Testing?
AB  - We developed an open-access, Excel-based model simulating currently recommended
      and alternative algorithms for adult HIV testing as a preliminary investigation
      of trade-offs between accuracy and costs. Despite higher costs, simpler HIV
      testing algorithms incorporating point of care nucleic acid testing may improve
      outcomes and thus merit additional research and field testing.

PMID- 30182031
TI  - The Impact of Acute Kidney Injury on the Risk of Mortality and Health Care
      Utilization Among Patients Treated With Polymyxins for Severe Gram-Negative
      Infections.
AB  - Background: With the rise of antibiotic resistance, polymyxin use has re-emerged
      but with a concern of renal toxicity. This study aims to assess mortality, length
      of stay, and total hospitalization cost associated with acute kidney injury (AKI)
      among recipients of intravenous (IV) sodium colistimethate (CMS) or IV polymyxin
      B (PMB). Methods: We conducted a retrospective database analysis using the
      Premier database from January 1, 2012, through September 30, 2015. Adults >=18
      years of age who were admitted for inpatient treatment with >=3 consecutive days
      of CMS or PMB were included. Generalized linear models compared patients who
      developed AKI with those who did not. Models were adjusted for patient and
      clinical characteristics. Results: A total of 4886 patients were included; 4103
      patients received CMS, and 783 received PMB. In the multivariable analyses, the
      presence of AKI was associated with higher in-hospital mortality in both the CMS
      cohort (adjusted odds ratio [aOR], 2.3; 95% confidence interval [CI], 1.9-2.7; P
      < .001) and the PMB cohort (aOR, 2.7; 95% CI, 1.8-4.2; P < .001). In both
      cohorts, patients who developed AKI experienced longer hospital stays (9.7 days
      and 11.6 days in the CMS and PMB cohorts, respectively; P < .001). The mean total
      hospitalization costs for patients who developed AKI were $47 820 higher (95% CI,
      $34 918-$60 722) in the CMS cohort and $35 244 higher (95% CI, $17 561-$52 928)
      in the PMB cohort. Conclusions: The clinical and economic burden of AKI in the
      context of polymyxin use is substantial. The use of effective antibiotics with
      limited toxicity should remain a priority.

PMID- 30182032
TI  - Cryptococcal Meningitis and Tuberculous Meningitis Co-infection in HIV-Infected
      Ugandan Adults.
AB  - We report 5 HIV-infected Ugandan adults with cryptococcal and tuberculous (TB)
      meningitis co-infection. All unmasked meningitis occurred within 5 weeks of
      starting HIV therapy. Xpert MTB/RIF Ultra facilitated prompt diagnosis; however,
      60% in-hospital mortality occurred. TB meningitis coinfection prevalence was 0.8%
      (5/586) among cryptococcal meningitis, 2 during second cryptococcal episodes.

PMID- 30182033
TI  - A Case of Delayed-Onset Posthypoxic Leukoencephalopathy in a Pediatric Patient.
AB  - We present a 16-year-old female status post traumatic brain injury from severe
      motor vehicle crash with prolonged extrication. Initially with a Glasgow Coma
      Scale of 4 and blood pressure of 80/40, she required emergent intubation. Head
      computed tomography was notable for skull fracture with hematoma, diffuse axonal
      injury, and 6-mm midline shift with right uncal herniation. On hospital day 1,
      she underwent decompressive R hemicraniectomy. She received neuroprotective
      treatment including a hypocarbic, hypernatremic state with close blood pressure
      monitoring for appropriate cerebral perfusion. On hospital day 4, patient was
      extubated and weaned off pressors and hypertonic saline. On hospital day 6, she
      was able to get out of bed to a chair, was speaking some words, following
      commands, and tolerating bites of food. On hospital day 8, she developed sudden
      agitation, combativeness, confusion, and could no longer follow commands.
      Magnetic resonance imaging now demonstrated confluent restricted diffusion
      consistent with acute changes. Imaging and examination findings were consistent
      with delayed-onset posthypoxic leukoencephalopathy.

PMID- 30182034
TI  - Lentivector Producer Cell Lines with Stably Expressed Vesiculovirus Envelopes.
AB  - Retroviral and lentiviral vectors often use the envelope G protein from the
      vesicular stomatitis virus Indiana strain (VSVind.G). However, lentivector
      producer cell lines that stably express VSVind.G have not been reported,
      presumably because of its cytotoxicity, preventing simple scale-up of vector
      production. Interestingly, we showed that VSVind.G and other vesiculovirus G from
      the VSV New Jersey strain (VSVnj), Cocal virus (COCV), and Piry virus (PIRYV)
      could be constitutively expressed and supported lentivector production for up to
      10 weeks. All G-enveloped particles were robust, allowing concentration and
      freeze-thawing. COCV.G and PIRYV.G were resistant to complement inactivation,
      and, using chimeras between VSVind.G and COCV.G, the determinant for complement
      inactivation of VSVind.G was mapped to amino acid residues 136-370. Clonal
      packaging cell lines using COCV.G could be generated; however, during attempts to
      establish LV producer cells, vector superinfection was observed following the
      introduction of a lentivector genome. This could be prevented by culturing the
      cells with the antiviral drug nevirapine. As an alternative countermeasure, we
      demonstrated that functional lentivectors could be reconstituted by admixing
      supernatant from stable cells producing unenveloped virus with supernatant
      containing envelopes harvested from cells stably expressing VSVind.G, COCV.G, or
      PIRYV.G.

PMID- 30182036
TI  - Mental Health and Disability Pension Onset: Changes in Consumption of Antianxiety
      and Hypnotic Drugs.
AB  - Introduction: In Norway, disability pension (DP) has been more prevalent over the
      later years, with mental disorders being a frequent cause. Previous analyses have
      questioned whether receiving DP is beneficial for mental health by considering
      changes in antidepressant drug consumption. To explore this further, we examined
      changes in antianxiety and hypnotic drug consumption following DP onset. Methods:
      Based on national Norwegian register data, this retrospective study encompassed
      8617 working-age individuals (25-50 years) who became DP during 2005 to 2013. We
      compared their benzodiazepines (BZD) and Z-hypnotic consumption 1 year pre- and
      postdisability pension onset. Results: About 80% of the individuals did not
      change their altogether benzodiazepine/Z-hypnotic consumption. Among individuals
      with an initial consumption <=1 defined daily dose (DDD), 18.9% increased their
      consumption to above 1 DDD. Individuals in the age-group 45 to 50 versus 24 to 34
      years had a lower risk of dose escalation (odds ratio [OR], 0.756, 95% confidence
      interval [CI]: 0.601-0.957). Individuals who used Z-hypnotics only had a higher
      risk of dose escalation compared to the joint benzodiazepine/Z-hypnotic user
      group (OR, 1.594, 95%CI: 1.284-1.970). Conclusion: In general, we cannot see that
      DP is associated with changes in benzodiazepine/Z-hypnotic consumption, but
      younger users and individuals using Z-hypnotics only had a greater risk of dose
      escalation compared to the older users and users with combined BZD and Z-hypnotic
      use.

PMID- 30182035
TI  - Disruption of the BCL11A Erythroid Enhancer Reactivates Fetal Hemoglobin in
      Erythroid Cells of Patients with beta-Thalassemia Major.
AB  - In the present report, we carried out clinical-scale editing in adult mobilized
      CD34+ hematopoietic stem and progenitor cells (HSPCs) using zinc-finger nuclease
      mediated disruption of BCL11a to upregulate the expression of gamma-globin (fetal
      hemoglobin). In these cells, disruption of the erythroid-specific enhancer of the
      BCL11A gene increased endogenous gamma-globin expression to levels that reached
      or exceeded those observed following knockout of the BCL11A coding region without
      negatively affecting survival or in vivo long-term proliferation of edited HSPCs
      and other lineages. In addition, BCL11A enhancer modification in mobilized CD34+
      cells from patients with beta-thalassemia major resulted in a readily detectable
      gamma-globin increase with a preferential increase in G-gamma, leading to an
      improved phenotype and, likely, a survival advantage for maturing erythroid cells
      after editing. Furthermore, we documented that both normal and beta-thalassemia
      HSPCs not only can be efficiently expanded ex vivo after editing but can also be
      successfully edited post-expansion, resulting in enhanced early in vivo
      engraftment compared with unexpanded cells. Overall, this work highlights a novel
      and effective treatment strategy for correcting the beta-thalassemia phenotype by
      genome editing.

PMID- 30182037
TI  - A New Approach to Fear of Falls From Connections With the Posttraumatic Stress
      Disorder Literature.
AB  - Fear of falling (FoF) is as an important psychological problem among older
      people. While it has been researched for around four decades, paradoxically there
      is no agreed definition of FoF. Confusion over the definition of FoF inhibits
      current understanding of empirical findings. The objective of this article is to
      critique current definitions of FoF and to present a novel theoretical model that
      aims to resolve theoretical misunderstanding. A narrative review was conducted to
      present definitions of FoF and concepts often conflated with it including fall
      related self-efficacy and anxiety. Then, by drawing on posttraumatic stress
      disorder (PTSD) theory and research, we present clear distinctions between the
      concepts. We argue that the presence or absence of anxiety determines whether FoF
      becomes maladaptive or adaptive, respectively, and that enhancing self-efficacy
      is key to optimizing postfall psychological recovery. The theoretical clarity
      presented will aid future research and application of evidence to the benefit
      older people.

PMID- 30182038
TI  - Preprocedural planning of transcatheter mitral valve interventions by
      multidetector CT: What the radiologist needs to know.
AB  - Mitral regurgitation is the most common valve disorder in the Western world, and
      although surgery is the established therapeutic gold standard, percutaneous
      transcatheter mitral interventions are gaining acceptance in selected patients
      who are inoperable or at an exceedingly high surgical risk. For such patients,
      multidetector computed tomography (MDCT) can provide a wealth of valuable
      morphological and functional information in the preoperative setting. Our aim is
      to give an overview of the MDCT image acquisition protocols, post-processing
      techniques, and imaging findings with which radiologists should be familiar to
      convey all relevant information to the Heart Team for successful treatment
      planning.

PMID- 30182039
TI  - Data on lithofacies, sedimentology and palaeontology of South Rifian Corridor
      sections (Morocco).
AB  - We provide lithological, sedimentological and micropalaeontological descriptions
      of 39 sections and boreholes crossing the upper Miocene deposits of the Rifian
      Corridor. These deposits represent the sedimentary remnants of the marine gateway
      that connected the Atlantic to the Mediterranean in the late Miocene. Results
      from these 39 sites were adopted to reconstruct the palaeogeographic evolution of
      the gateway presented in the associated research article (Capella et al., 2018)
      [1]. For each outcrop we present a synthesis of field observations, lithofacies,
      key sedimentological features, planktic and benthic assemblages.

PMID- 30182040
TI  - Photocatalytic degradation data of benzene and toluene by ZnO coated on glass
      plates under simulated sunlight.
AB  - For this data article the photocatalytic oxidation of benzene and toluene by ZnO
      nanoparticles coated on glass plates were studied under simulated sunlight. ZnO
      nanoparticles were coated on three glass plates by heat attachment methods. To
      evaluate the photocatalytic removal of benzene and toluene, coated plates
      irradiated by metal halide lamp in a rectangular reactor in batch mode. The
      effect of initial pollutants concentration, temperature, relative humidity,
      irradiation time, concentration of zinc oxide suspension, were assessed. The
      surface morphology and structure of ZnO nanoparticles and ZnO coated on glass
      plates were characterized by scanning electron microscopy, X-ray diffraction and
      Field Emission Scanning Electron Microscopy. Sampling and analysis of pollutants
      were performed according to the National Institute for Occupational Safety and
      Health (NIOSH) method. To analyze the concentration of benzene and toluene, gas
      chromatography with flame ionization detector (GC-FID) was used. The data results
      indicated that photocatalytic process by ZnO under irradiation of metal halide
      lamp could remove benzene and toluene at optimum experimental conditions. Coating
      of glass surfaces by ZnO suspension, resulted in 46% and 57% removal of benzene
      and toluene as concentration of 50 ppm at 45  degrees C, and relative humidity of
      40% after 240 min irradiation of metal halide lamp.

PMID- 30182041
TI  - Comparison between experimental and satellite temperature datasets in Covenant
      University.
AB  - This article contains the ground and satellite meteorological data sets of clear
      sky temperature events for five years (2012-2016) in Covenant University, Ota,
      Ogun State, Nigeria. The satellite data were obtained from Atmospheric Infrared
      Sounder (AIRS) while the ground data information were acquired from Davis weather
      station data logger-vantage pro2. These data were acquired from propagation study
      that used same location (Lat: 6.67 degrees N and Long: 3.23 degrees E) for both
      satellite data and radiometer directed along the same path by providing
      information about the temperature. The data sets were assessed and evaluated by
      means of a descriptive statistics. There was perfect agreement between the two
      data. The peak temperature events occurs between the months of November and April
      for the five years of observation for both Ota and AIRS Satellite. The data from
      this article can be used for further studies on non-rainy attenuation effect in
      the study area.

PMID- 30182042
TI  - Data set on Rapid Diagnostic Tests (RDTs) and microscopy for diagnosing
      plasmodium falciparum and plasmodium vivax.
AB  - The World Heal Organization (WHO) has identified malaria diagnosis as being
      pivotal to eradicating the disease by 2030 as stipulated in the Sustainable
      Development Goals (SDG). The data presented here was obtained from outpatients of
      a hospital in the South Western Region of Nigeria from November 2016 to May 2017.
      The data contains malaria incidence amongst asymptomatic and symptomatic
      outpatients in the period under review. Malaria incidence was obtained using two
      diagnostic test kits, Bioline SD (HRP-2) and ACON (HRP-2/Aldolase) alongside
      Microscopy as gold standard. Specificity, Sensitivity and Kappa statistic of each
      test device is presented in the tables herewith. Data presented here could be
      used alongside other data sources to assess the state of malaria diagnostics.

PMID- 30182043
TI  - Tumor Suppressor Down-Regulation Promotes Hepatocyte Proliferation: A New
      GANKster on the Block.

PMID- 30182044
TI  - Hidden Dangers of Antibiotic Use: Increased Gut Permeability Mediated by
      Increased Pancreatic Proteases Reaching the Colon.

PMID- 30182045
TI  - Colon Cancers Get a Negative (Selection) Attitude.

PMID- 30182046
TI  - Ulcerative Colitis-Associated Carcinoma: Epithelial SMAD4-Mediated Signaling Is a
      Key Guardian.

PMID- 30182047
TI  - The Next MacGyver: A Platform to Study Intestinal Organoids Using High-Throughput
      Computer-Driven Microinjection.

PMID- 30182048
TI  - TRPV1 Sensory Neurons and Enteric Glia in ENS Link Tachykinins to
      Neuroinflammation and Nociception.

PMID- 30182049
TI  - Experimental Models for Studying Food Allergy.
AB  - Immunoglobulin E-mediated food allergy is rapidly developing into a global health
      problem. Publicly available therapeutic intervention strategies are currently
      restricted to allergen avoidance and emergency treatments. To gain a better
      understanding of the disease pathophysiology so that new therapies can be
      developed, major research efforts have been put into studying food allergy in
      mice. Animal models should reflect the human pathology as closely as possible to
      allow for a rapid translation of basic science observations to the bedside. In
      this regard, experimental models of food allergy provide significant challenges
      for research because of discrepancies between the presentation of disease in
      humans and mice. The goal of this review is to give a summary of commonly used
      murine disease models and to discuss how they relate to the human condition. We
      will focus on epicutaneous sensitization models, on mouse strains that sensitize
      spontaneously to food as seen in humans, and on models in humanized animals. In
      summary, expanding the research toolbox of experimental food allergy provides an
      important step toward closing gaps in our understanding of the derailing immune
      mechanism that underlies the human disease. The availability of additional
      experimental models will provide exciting opportunities to discover new
      intervention points for the treatment of food allergies. (Cell Mol Gastroenterol
      Hepatol 2018;x:x).

PMID- 30182050
TI  - Increased Pancreatic Protease Activity in Response to Antibiotics Impairs Gut
      Barrier and Triggers Colitis.
AB  - Background & Aims: Antibiotic (ABx) therapy is associated with increased risk for
      Crohn's disease but underlying mechanisms are unknown. We observed high fecal
      serine protease activity (PA) to be a frequent side effect of ABx therapy. The
      aim of the present study was to unravel whether this rise in large intestinal PA
      may promote colitis development via detrimental effects on the large intestinal
      barrier. Methods: Transwell experiments were used to assess the impact of high PA
      in ABx-treated patients or vancomycin/metronidazole-treated mice on the
      epithelial barrier. Serine protease profiling was performed using liquid
      chromatography-mass spectrometry/mass spectrometry analysis. The impact of high
      large intestinal PA on the intestinal barrier in wild-type and interleukin (IL)10
      /- mice and on colitis development in IL10-/- mice was investigated using
      vancomycin/metronidazole with or without oral serine protease inhibitor (AEBSF)
      treatment. Results: The ABx-induced, high large intestinal PA was caused by
      significantly increased levels of pancreatic proteases and impaired epithelial
      barrier integrity. In wild-type mice, the rise in PA caused a transient increase
      in intestinal permeability but did not affect susceptibility to chemically
      induced acute colitis. In IL10-/- mice, increased PA caused a consistent
      impairment of the intestinal barrier associated with inflammatory activation in
      the large intestinal tissue. In the long term, the vancomycin/metronidazole
      induced lasting increase in PA aggravated colitis development in IL10-/- mice.
      Conclusions: High large intestinal PA is a frequent adverse effect of ABx
      therapy, which is detrimental to the large intestinal barrier and may contribute
      to the development of chronic intestinal inflammation in susceptible individuals.

PMID- 30182051
TI  - Severe Iron Metabolism Defects in Mice With Double Knockout of the Multicopper
      Ferroxidases Hephaestin and Ceruloplasmin.
AB  - Background & Aims: Multicopper ferroxidases (MCFs) facilitate intestinal iron
      absorption and systemic iron recycling, likely by a mechanism involving the
      oxidization of Fe2+ from the iron exporter ferroportin 1 for delivery to the
      circulating Fe3+ carrier transferrin. Hephaestin (HEPH), the only MCF known to be
      expressed in enterocytes, aids in the basolateral transfer of dietary iron to the
      blood. Mice lacking HEPH in the whole body (Heph-/- ) or intestine alone
      (Hephint/int ) exhibit defects in dietary iron absorption but still survive and
      grow. Circulating ceruloplasmin (CP) is the only other known MCF likely to
      interact with enterocytes. Our aim was to assess the effects of combined deletion
      of HEPH and CP on intestinal iron absorption and homeostasis in mice. Methods:
      Mice lacking both HEPH and CP (Heph-/-Cp-/- ) and mice with whole-body knockout
      of CP and intestine-specific deletion of HEPH (Hephint/intCp-/- ) were generated
      and phenotyped. Results: Heph-/-Cp-/- mice were severely anemic and had low serum
      iron, but they exhibited marked iron loading in duodenal enterocytes, the liver,
      heart, pancreas, and other tissues. Hephint/intCp-/- mice were moderately anemic
      (similar to Cp-/- mice) but were iron loaded only in the duodenum and liver, as
      in Hephint/int and Cp-/- mice, respectively. Both double knockout models absorbed
      iron in radiolabeled intestinal iron absorption studies, but the iron was
      inappropriately distributed, with an abnormally high percentage retained in the
      liver. Conclusions: These studies indicate that HEPH and CP, and likely MCFs in
      general, are not essential for intestinal iron absorption but are required for
      proper systemic iron distribution. They also point to important extra-intestinal
      roles for HEPH in maintaining whole-body iron homeostasis.

PMID- 30182052
TI  - Self-efficacy, sensation seeking, right attitude, and readiness to change among
      alcohol drinkers in a Thai vocational school.
AB  - Introduction: The prevalence of alcohol use in teenagers has been increasing
      every year. The majority of alcohol drinkers were vocational students when
      compared with other educational settings. Sixty percent of Thai vocational
      students were found to use alcohol. Methods: Our research was a cross-sectional
      study in 306 vocational students, using the Alcohol Consumption Questionnaire,
      the ASSIST-Y (Alcohol, Smoking, and Substance Involvement Screening Test-Youth)
      screening tool and a self-administered questionnaire. The association between
      alcohol drinking with sensation seeking, self-efficacy, right attitude and
      readiness to change factors were analyzed by binary logistic regression. Results:
      Most students were males (57.5%) and 15-17 years of age (70.9%). Seventy-six
      point eight percent of vocational students were in the lifetime drinker group.
      The binge drinker group was 32.7% and 10.5% were classified in a light drinker
      group. Sensation seeking was strongly associated with the binge drinker group and
      the light drinker group, especially the disinhibition dimension (adjusted odds
      ratio [OR] = 1.64, 95% CI: 1.34-2.00 and [OR] = 1.57, 95% CI: 1.19-2.06,
      respectively). Conclusions: Our research found sensation seeking, especially the
      disinhibition dimension was a significant factor for monitoring drinking
      behavior. We recommended that every vocational student should be monitored for
      sensation seeking factors.

PMID- 30182053
TI  - Sex differences in the association between apolipoprotein E epsilon4 allele and
      Alzheimer's disease markers.
AB  - Introduction: We determined whether the effect of apolipoprotein E (APOE)
      epsilon4 genotype on Alzheimer's disease (AD) markers differs in men and women
      across AD stages. Methods: Among normal control (NC) participants (N = 702) and
      participants with mild cognitive impairment (N = 576) and AD (N = 305), we
      examined the associations of sex and APOE-epsilon4 carrier status with cortical
      amyloid-beta (Abeta) burden, hippocampal volume ratio (HpVR; hippocampal
      volume/intracranial volume * 103), brain glucose metabolism, and verbal memory.
      Results: In NC, APOE-epsilon4 related to greater Abeta burden and poorer verbal
      memory across sex but to smaller HpVR and hypometabolism in men only. In mild
      cognitive impairment, APOE-epsilon4 related to smaller HpVR, hypometabolism,
      greater Abeta burden, and poorer verbal memory across sex. In AD, APOE-epsilon4
      related to greater Abeta burden in men only and smaller HpVR across sex and
      showed no association with hypometabolism or verbal memory. Discussion: Sex
      differences in the association between APOE-epsilon4 and AD markers vary by
      disease stage.

PMID- 30182054
TI  - NF1 deficiency correlates with estrogen receptor signaling and diminished
      survival in breast cancer.
AB  - The key negative regulatory gene of the RAS pathway, NF1, is mutated or deleted
      in numerous cancer types and is associated with increased cancer risk and drug
      resistance. Even though women with neurofibromatosis (germline NF1 mutations)
      have a substantially increased breast cancer risk at a young age and NF1 is
      commonly mutated in sporadic breast cancers, we have a limited understanding of
      the role of NF1 in breast cancer. We utilized CRISPR-Cas9 gene editing to create
      Nf1 rat models to evaluate the effect of Nf1 deficiency on tumorigenesis. The
      resulting Nf1 indels induced highly penetrant, aggressive mammary adenocarcinomas
      that express estrogen receptor (ER) and progesterone receptor (PR). We identified
      distinct Nf1 mRNA and protein isoforms that were altered during tumorigenesis. To
      evaluate NF1 in human breast cancer, we analyzed genomic changes in a data set of
      2000 clinically annotated breast cancers. We found NF1 shallow deletions in 25%
      of sporadic breast cancers, which correlated with poor clinical outcome. To
      identify biological networks impacted by NF1 deficiency, we constructed gene co
      expression networks using weighted gene correlation network analysis (WGCNA) and
      identified a network connected to ESR1 (estrogen receptor). Moreover, NF1
      deficient cancers correlated with established RAS activation signatures. Estrogen
      dependence was verified by estrogen-ablation in Nf1 rats where rapid tumor
      regression was observed. Additionally, Nf1 deficiency correlated with increased
      estrogen receptor phosphorylation in mammary adenocarcinomas. These results
      demonstrate a significant role for NF1 in both NF1-related breast cancer and
      sporadic breast cancer, and highlight a potential functional link between
      neurofibromin and the estrogen receptor.

PMID- 30182055
TI  - Image analysis with deep learning to predict breast cancer grade, ER status,
      histologic subtype, and intrinsic subtype.
AB  - RNA-based, multi-gene molecular assays are available and widely used for patients
      with ER-positive/HER2-negative breast cancers. However, RNA-based genomic tests
      can be costly and are not available in many countries. Methods for inferring
      molecular subtype from histologic images may identify patients most likely to
      benefit from further genomic testing. To identify patients who could benefit from
      molecular testing based on H&E stained histologic images, we developed an image
      analysis approach using deep learning. A training set of 571 breast tumors was
      used to create image-based classifiers for tumor grade, ER status, PAM50
      intrinsic subtype, histologic subtype, and risk of recurrence score (ROR-PT). The
      resulting classifiers were applied to an independent test set (n = 288), and
      accuracy, sensitivity, and specificity of each was assessed on the test set.
      Histologic image analysis with deep learning distinguished low-intermediate vs.
      high tumor grade (82% accuracy), ER status (84% accuracy), Basal-like vs. non
      Basal-like (77% accuracy), Ductal vs. Lobular (94% accuracy), and high vs. low
      medium ROR-PT score (75% accuracy). Sampling considerations in the training set
      minimized bias in the test set. Incorrect classification of ER status was
      significantly more common for Luminal B tumors. These data provide proof of
      principle that molecular marker status, including a critical clinical biomarker
      (i.e., ER status), can be predicted with accuracy >75% based on H&E features.
      Image-based methods could be promising for identifying patients with a greater
      need for further genomic testing, or in place of classically scored variables
      typically accomplished using human-based scoring.

PMID- 30182056
TI  - Toward digitally controlled catalyst architectures: Hierarchical nanoporous gold
      via 3D printing.
AB  - Monolithic nanoporous metals, derived from dealloying, have a unique bicontinuous
      solid/void structure that provides both large surface area and high electrical
      conductivity, making them ideal candidates for various energy applications.
      However, many of these applications would greatly benefit from the integration of
      an engineered hierarchical macroporous network structure that increases and
      directs mass transport. We report on 3D (three-dimensional)-printed hierarchical
      nanoporous gold (3DP-hnp-Au) with engineered nonrandom macroarchitectures by
      combining 3D printing and dealloying. The material exhibits three distinct
      structural length scales ranging from the digitally controlled macroporous
      network structure (10 to 1000 MUm) to the nanoscale pore/ligament morphology (30
      to 500 nm) controlled by dealloying. Supercapacitance, pressure drop, and
      catalysis measurements reveal that the 3D hierarchical nature of our printed
      nanoporous metals markedly improves mass transport and reaction rates for both
      liquids and gases. Our approach can be applied to a variety of alloy systems and
      has the potential to revolutionize the design of (electro-)chemical plants by
      changing the scaling relations between volume and catalyst surface area.

PMID- 30182057
TI  - Photothermal trap utilizing solar illumination for ice mitigation.
AB  - Ice buildup is an operational and safety hazard in wind turbines, power lines,
      and airplanes. Traditional deicing methods, including mechanical and chemical
      means, are energy-intensive or environmentally unfriendly. Superhydrophobic anti
      icing surfaces, while promising, can become ineffective due to frost formation
      within textures. We report on a "photothermal trap"-a laminate applied to a base
      substrate-that can efficiently deice by converting solar illumination to heat at
      the ice-substrate interface. It relies on the complementing properties of three
      layers: a selective absorber for solar radiation, a thermal spreader for lateral
      dispersal of heat, and insulation to minimize transverse heat loss. Upon
      illumination, thermal confinement at the heat spreader leads to rapid increase of
      the surface temperature, thereby forming a thin lubricating melt layer that
      facilitates ice removal. Lateral heat spreading overcomes the unavoidable
      shadowing of certain areas from direct illumination. We provide a design map that
      captures the key physics guiding illumination-induced ice removal. We demonstrate
      the deicing performance of the photothermal trap at very low temperatures, and
      under frost and snow coverage, via laboratory-scale and outdoor experiments.

PMID- 30182058
TI  - Acoustophoretic printing.
AB  - Droplet-based printing methods are widely used in applications ranging from
      biological microarrays to additive manufacturing. However, common approaches,
      such as inkjet or electrohydrodynamic printing, are well suited only for
      materials with low viscosity or specific electromagnetic properties,
      respectively. While in-air acoustophoretic forces are material-independent, they
      are typically weak and have yet to be harnessed for printing materials. We
      introduce an acoustophoretic printing method that enables drop-on-demand
      patterning of a broad range of soft materials, including Newtonian fluids, whose
      viscosities span more than four orders of magnitude (0.5 to 25,000 mPa.s) and
      yield stress fluids (tau0 > 50 Pa). By exploiting the acoustic properties of a
      subwavelength Fabry-Perot resonator, we have generated an accurate, highly
      localized acoustophoretic force that can exceed the gravitational force by two
      orders of magnitude to eject microliter-to-nanoliter volume droplets. The
      versatility of acoustophoretic printing is demonstrated by patterning food,
      optical resins, liquid metals, and cell-laden biological matrices in desired
      motifs.

PMID- 30182059
TI  - Encoding canonical DNA quadruplex structure.
AB  - The main challenge in DNA quadruplex design is to encode a three-dimensional
      structure into the primary sequence, despite its multiple, repetitive guanine
      segments. We identify and detail structural elements describing all 14 feasible
      canonical quadruplex scaffolds and demonstrate their use in control of design.
      This work outlines a new roadmap for implementation of targeted design of
      quadruplexes for material, biotechnological, and therapeutic applications.

PMID- 30182060
TI  - Robust optical polarization of nuclear spin baths using Hamiltonian engineering
      of nitrogen-vacancy center quantum dynamics.
AB  - Dynamic nuclear polarization (DNP) is an important technique that uses
      polarization transfer from electron to nuclear spins to achieve nuclear
      hyperpolarization. Combining efficient DNP with optically polarized nitrogen
      vacancy (NV) centers offers promising opportunities for novel technological
      applications, including nanoscale nuclear magnetic resonance spectroscopy of
      liquids, hyperpolarized nanodiamonds as magnetic resonance imaging contrast
      agents, and the initialization of nuclear spin-based diamond quantum simulators.
      However, none of the current realizations of polarization transfer are
      simultaneously robust and sufficiently efficient, making the realization of the
      applications extremely challenging. We introduce the concept of systematically
      designing polarization sequences by Hamiltonian engineering, resulting in
      polarization sequences that are robust and fast. We theoretically derive
      sequences and experimentally demonstrate that they are capable of efficient
      polarization transfer from optically polarized NV centers in diamond to the
      surrounding 13C nuclear spin bath even in the presence of control errors, making
      the abovementioned novel applications possible.

PMID- 30182061
TI  - Preputial Graft Ureteroplasty for the Treatment of Complex Ureteral Stricture: A
      New Surgical Technique and Review of Literature.
AB  - Objectives: To present our first experience and 12-month outcomes of the novel
      technique of onlay preputial graft ureteroplasty (PGU) for complex ureteral
      stricture. Methods: In December 2016, open onlay PGU was made on a male patient
      who have proximal stricture of the right ureter. The length of upper ureteral
      stricture was 50 mm. A 60 mm in length and 15 mm in width preputial graft was
      harvested from the ventral side of the penis and placed in the ureter as a
      ventral onlay for ureteroplasty. Operative time, intraoperative, and
      postoperative complications were recorded properly. Follow-up was performed via
      clinical assessment of symptoms, renal ultrasound, MR urography, and nuclear scan
      renography. Results: The new technique was effectively performed without any
      intraoperative and postoperative complications. Residual hydronephrosis in the
      right side was found through ultrasonography 3, 6, and 12 months and MR urography
      6 months postoperatively. But complaint of the patient's pain passed completely.
      Conclusions: Within our knowledge, we present the first experience with onlay PGU
      for proximal ureteral stricture. Twelve-month results indicate that the new
      technique appears to be an excellent option for proximal ureteral stricture. Our
      experience is encouraging, and it will find wider application in the complex
      ureteral lesion.

PMID- 30182062
TI  - Transthesia: Comparing the Prevalence of Synesthesia in Transgender and Cisgender
      Individuals.
AB  - Purpose: To evaluate the prevalence of synesthesia in transgender versus
      cisgender individuals. Methods: A 10-question, self-administered written survey,
      developed to assess the prevalence of synesthesia, was distributed to transgender
      individuals (n=96) attending support groups as well as to cisgender participants
      (n=103) identified among individuals accompanying transgender attendees.
      Demographic data and prevalence of synesthesia were analyzed using descriptive
      statistics. Differences between groups were analyzed using a chi-square test.
      Results: Forty-two percent of transgender participants endorsed synesthesia
      compared with 16% of cisgender participants. These findings persisted when
      analyzed by specific gender identity (i.e., male, female, and nonbinary).
      Conclusion: This study suggests a correlation between synesthesia and transgender
      identity that may indicate a common biological cause. Limitations of this study
      include use of a survey that has not yet been validated. Initial findings may
      justify further research.

PMID- 30182063
TI  - A retrospective analysis of health-related quality of life in adolescent
      idiopathic scoliosis children treated by anterior instrumentation and fusion.
AB  - Background: Idiopathic scoliosis is the most common type of spinal deformity.
      Scoliosis is defined as a lateral curvature of the spine greater than 10 degrees 
      accompanied by rotation of the vertebrae. The treatment available for adolescent
      idiopathic scoliosis is observation, orthosis, and surgery. The surgical options
      include open anterior release and instrumentation, posterior instrumentation, and
      thoracoscopic approaches. The Scoliosis Research Society Questionnaire (SRS-30)
      is a specific instrument to measure health-related quality of life in patients
      with scoliosis, who had or had not undergone surgery. The purpose was to assess
      the post-operative functional outcome using SRS-30 in children who underwent
      anterior release, instrumentation, and fusion using autogenous rib graft for
      adolescent idiopathic scoliosis (AIS). Methods: In a retrospective cohort study,
      25 patients between the ages of 11 and 17 years, who underwent anterior release,
      instrumentation, and fusion using autogenous rib graft for adolescent idiopathic
      scoliosis (AIS) between 2008 and 2014, were included in the study. Results: The
      total average score was 4.26 with a SD of 0.014 and had maximum average score 4.5
      (for pain) and minimum average score 3.8 (for self-image). Conclusion: Anterior
      release, instrumentation, and fusion using autogenous rib graft is having good
      functional outcome in all domains.

PMID- 30182064
TI  - A platform for phenotypic discovery of therapeutic antibodies and targets applied
      on Chronic Lymphocytic Leukemia.
AB  - Development of antibody drugs against novel targets and pathways offers great
      opportunities to improve current cancer treatment. We here describe a phenotypic
      discovery platform enabling efficient identification of therapeutic antibody
      target combinations. The platform utilizes primary patient cells throughout the
      discovery process and includes methods for differential phage display cell
      panning, high-throughput cell-based specificity screening, phenotypic in vitro
      screening, target deconvolution, and confirmatory in vivo screening. In this
      study the platform was applied on cancer cells from patients with Chronic
      Lymphocytic Leukemia resulting in discovery of antibodies with improved
      cytotoxicity in vitro compared to the standard of care, the CD20-specific
      monoclonal antibody rituximab. Isolated antibodies were found to target six
      different receptors on Chronic Lymphocytic Leukemia cells; CD21, CD23, CD32,
      CD72, CD200, and HLA-DR of which CD32, CD200, and HLA-DR appeared as the most
      potent targets for antibody-based cytotoxicity treatment. Enhanced antibody
      efficacy was confirmed in vivo using a patient-derived xenograft model.

PMID- 30182065
TI  - Oral administration of dibutyryl adenosine cyclophosphate improved growth
      performance in weaning piglets by enhancing lipid fatty acids metabolism.
AB  - Dibutyryl adenosine cyclophosphate (dbcAMP-Ca), an analog of cyclic adenosine
      monophosphate (cAMP), plays greater roles in regulating physiological activities
      and energy metabolism than cAMP. The aim of this study was to investigate the
      effect of oral administration of dbcAMP-Ca on growth performance and fatty acids
      metabolism in weaning piglets. A total of 14 early weaning piglets (7 +/- 1 d of
      age, 3.31 +/- 0.09 kg, Landrace * Large White * Duroc) were randomly divided into
      2 groups: control group and dbcAMP-Ca group, and the piglets received 7 mL of
      0.9% NaCl or 1.5 mg dbcAMP-Ca dissolved in 7 mL of 0.9% NaCl per day for 10 d,
      respectively. The results showed that the average daily gain (ADG) increased by
      109.17% (P < 0.05) in the dbcAMP-Ca group compared with the control group.
      Besides, dbcAMP-Ca significantly decreased blood high density lipoprotein
      cholesterol (HDLC) concentration (P < 0.05) and significantly increased blood low
      density lipoprotein cholesterol (LDLC) concentration (P < 0.05) compared with the
      control group. Further, liver C18:2n6t content significantly increased in dbcAMP
      Ca group (P < 0.05) compared with the control group. With the increase of
      C18:2n6t content, the mRNA expression levels of peroxisome proliferator-activated
      receptor alpha (PPARalpha) and hormone sensitive glycerol three lipase (HSL), of
      which genes are related to lipid metabolism, were also significantly increased (P
      < 0.05 or P < 0.01). All of the results indicated that dbcAMP-Ca improved the
      ADG, which was probably done by regulating fatty acids metabolism in the liver of
      weaning piglets.

PMID- 30182066
TI  - Analysis of oral microorganism diversity in healthy individuals before and after
      chewing areca nuts using PCR-denatured gradient gel electrophoresis.
AB  - To analyze oral microbial diversity in the saliva of 8 healthy individuals before
      and after chewing areca nuts. Saliva samples were collected before chewing areca
      nuts, after chewing areca nuts for 5 min and after chewing areca nuts for 30 min.
      DNA was extracted, and microbial diversity was examined using PCR-denaturing
      gradient gel electrophoresis (PCR-DGGE). When examining DGGE profiles
      collectively, the bands associated with Streptococcus and Veillonella were the
      most intense, making them the most prevalent bacteria. Furthermore, the band
      intensities did not decrease after chewing areca nuts for 5 or 30 min; thus,
      these bacteria were unaffected. However, when examining some individuals, the
      band intensities for Streptococcus and Veillonella became more intense after 5
      min of chewing and then returned to the pre-chewing level. This difference may be
      attributed to the mechanical movements of the oral cavity or individual
      differences. Other bacteria, such as Neisseria, Actinomycetes, and Rothia
      dentocariosa, were also found to have an increased or decreased prevalence
      following areca nut-chewing. Since the predominant species that are present
      following areca nut-chewing include Streptococcus and Veillonella, it would seem
      likely that these bacteria play an important role in the periodontal diseases
      associated with areca chewing.

PMID- 30182067
TI  - Attitudes towards family formation among men attending fertility counselling.
AB  - Men and women are increasingly postponing childbearing until an age where
      fertility has decreased, meaning that they might have difficulties in achieving
      their desired family size. This study explored childless men's attitudes towards
      family formation. Data were collected through semi-structured qualitative
      interviews with 21 men attending the Fertility Assessment and Counselling Clinic
      in Copenhagen or Horsens, Denmark. Data were analysed using content analysis. The
      men envisioned a nuclear family with their own biological children, but they
      experienced doubts and ambivalence about parenthood and feeling 'ready'. Their
      lack of readiness was linked to their awareness of the sacrifices and costs
      involved with parenthood, and their belief that they could safely delay
      parenthood. The men did not consider that they may be unable to have their own
      biological children. This study highlights the importance of considering men's
      attitudes and preferences towards family formation when understanding couples'
      decision-making. Contrary to common understanding, the findings show that men are
      as concerned with the planning and timing of parenthood as women, but their
      knowledge of the age-related decline in fertility is poor. Men need to gain more
      awareness of the limitations of fertility and the impact of female and male age
      on the ability to achieve parenthood aspirations.

PMID- 30182068
TI  - Master protocol trials in oncology: Review and new trial designs.
AB  - In oncology, next generation sequencing and comprehensive genomic profiling have
      enabled the detailed classification of tumors using molecular biology. However,
      it is unrealistic to conduct phase I-III trials according to each sub-population
      based on patient molecular subtypes. Common protocols that assess the combination
      of several molecular markers and their targeted therapies by means of multiple
      sub-studies are required. These protocols are called "master protocols," and are
      drawing attention as a next-generation clinical trial design. Recently, several
      reviews of clinical trials based on the master protocol design have been
      published, but their definitions of these such trials, including basket,
      umbrella, and platform trials, were not consistent. Concurrently, the
      acceleration of the development of new statistical designs for master protocol
      trials has been underway. This article provides an overview of recent reviews for
      master protocols, including their statistical design methodologies in Oncology.
      We also introduce several examples of previous and on-going master protocol
      trials along with their classifications by some recent studies.

PMID- 30182069
TI  - Usefulness of B-scan ocular ultrasound images for diagnosis of optic
      perineuritis.
AB  - Purpose: This study was performed to examine the usefulness of B-scan ocular
      ultrasound images for the diagnosis of optic perineuritis. Observations: A 72
      year-old woman developed nonpainful blurred vision in her left eye. At the first
      ophthalmological consultation, she had optic disc swelling and choroidal folds in
      both eyes and subretinal fluid in the left eye. She was referred to our clinic 1
      month after symptom onset. At the first visit to our clinic, she still complained
      of blurred vision. She was found to have mild vitreous cells in the left eye and
      optic disc swelling in both eyes. However, the choroidal folds had already
      resolved in both eyes. B-scan ultrasound images displayed the optic nerve sheath
      as a highly reflective circle with shadowing around the optic disc in both eyes
      and scleral thickening in the left eye with fluid in sub-Tenon's space. Bilateral
      optic perineuritis with posterior scleritis seemed highly plausible. Magnetic
      resonance imaging with intravenous contrast revealed increased signal intensity
      around the optic nerve (i.e., the "tram track sign") in both eyes, which was
      consistent with optic perineuritis. Conclusion and importance: Optic perineuritis
      is a rare inflammatory disorder involving the optic nerve sheath. Although
      magnetic resonance imaging is reportedly useful for diagnosis of this disease, no
      previous reports have described B-scan ultrasound imaging for this purpose. We
      herein provide the first report of a patient suspected to have optic perineuritis
      based on B-scan images. B-scan ultrasound may be useful for diagnosis of optic
      perineuritis, especially with inflammation surrounding the optic nerve.

PMID- 30182070
TI  - Bilateral simultaneous central retinal vein occlusion in hyperviscosity
      retinopathy treated with systemic immunosuppressive therapy only.
AB  - Purpose: To describe the clinical presentation and imaging features of a patient
      presenting with bilateral central retinal vein occlusion (CRVO), who was
      subsequently diagnosed with hyperviscosity retinopathy due to B cell
      lymphoproliferative disease, and had a good response to systemic
      immunosuppressive therapy. Observations: A clinical case report of an 87-year-old
      woman who presented with bilateral CRVO. Visual acuity, clinical examination,
      spectral domain optical coherence tomography (SD-OCT), color fundus photography
      and systemic evaluation were obtained. Ocular examination at presentation
      revealed bilateral CRVO, and OCT examination revealed significant central macular
      edema bilaterally. Six months after the diagnosis of hyperviscosity retinopathy
      and administration of systemic cyclophosphamide immunosuppressive therapy for B
      cell lymphoproliferative disease, most of the retinal hemorrhages resolved and
      partial resolution of the macular edema in the left eye was observed. Conclusion
      and Importance: This case describes the association between bilateral
      simultaneous CRVO and hyperviscosity. Under unique circumstances our patient
      received systemic therapy alone, without plasmapheresis. Although only limited
      therapy was applied, she didn't have deterioration or recurrent events; she had a
      small improvement in her macular edema and a significant improvement in her
      systemic functional state as well as reduction in her monoclonal IGM level.

PMID- 30182071
TI  - Exploring cutting-edge hydrogel technologies and their biomedical applications.

PMID- 30182072
TI  - The effect of tensile and fluid shear stress on the in vitro degradation of
      magnesium alloy for stent applications.
AB  - Magnesium alloys have gained great attention as biodegradable materials for stent
      applications. Cardiovascular stents are continuously exposed to different types
      of mechanical loadings simultaneously during service, including tensile,
      compressive and fluid shear stress. In this study, the in vitro degradation of
      WE43 wires was investigated under combined effect of tensile loading and fluid
      shear stress and compared with that experienced an individual loading condition.
      For the individual mechanical loading treatment, the degradation of magnesium
      wires was more severely affected by tensile loading than fluid shear stress.
      Under tensile loading, magnesium wires showed faster increment of corrosion
      rates, loss of mechanical properties and localized corrosion morphology with the
      increasing tensile loadings. With the combined stress, smaller variation of the
      corrosion rates as well as the slower strength degeneration was shown with
      increasing stress levels, in comparison with the individual treatment of tensile
      loading. This study could help to understand the effect of complex stress
      condition on the corrosion of magnesium for the optimization of biodegradable
      magnesium stents.

PMID- 30182073
TI  - Immune checkpoint inhibitors for urothelial carcinoma.
AB  - Urothelial carcinoma (UC), originating in the bladder or upper urinary tract, is
      the most common histological type of cancer. Currently, platinum-based cytotoxic
      chemotherapy is the standard treatment for metastatic UC (mUC) and the preferred
      treatment option in the perioperative (neoadjuvant and/or adjuvant) setting of
      muscle invasive bladder cancer (MIBC). In addition, intravesical bacillus
      Calmette-Guerin immunotherapy or chemotherapy is applied as the adjuvant
      therapeutic option in non-muscle invasive bladder cancer (NMIBC) after
      transurethral resection, to prevent recurrence and progression. In recent years,
      with an increased understanding of cancer immunobiology, systemic immunotherapies
      targeting immune checkpoint inhibition has been explored and clinically used in
      the area of UC. The programmed cell death 1 receptor (PD-1) and its ligand (PD
      L1) are important negative regulators of immune activity, preventing the
      destruction of normal tissues and autoimmunity. To date, five immune checkpoint
      inhibitors blocking PD-1 (pembrolizumab, nivolumab) or PD-L1 (atezolizumab,
      durvalumab, and avelumab) have been approved by the United States Food and Drug
      Administration (US-FDA) for first- or second-line use in mUC, based on durable
      therapeutic response and manageable safety profiles observed in relevant clinical
      trials. In addition, the clinical use of several immune checkpoint inhibitors is
      currently being tested for MIBC and NMIBC. In this article, we review the current
      and ongoing clinical trials, regarding immune checkpoint inhibitors, being
      conducted in various clinical settings of UC, including mUC, MIBC, and NMIBC.

PMID- 30182074
TI  - Readability assessment of commonly used urological questionnaires.
AB  - Purpose: This study was performed to assess readability of the most commonly used
      questionnaires in urology including a separate analysis of their single-items to
      identify questions that might be especially demanding for patients. Materials and
      Methods: The guidelines of the European Association of Urology were screened for
      recommended questionnaires. Readability was analyzed for complete questionnaires
      as well as their single-items separately using well established readability
      assessment tools, including Flesch-Kincaid grade level (FKGL), Simple Measure of
      Gobbledygook grade level (SMOG), Coleman-Liau Index (CLI), Gunning-Fog Index, and
      the Flesch Reading Ease formula. Results: A total of 13 questionnaires were
      included to the analysis. Calculation of grade levels (FKGL, SMOG, CLI, FGI)
      showed readability scores of 2.7th to 16.7th grade. Easiest readability as
      calculated by median grade levels was found for the short form of the
      International Consultation on Incontinence Questionnaires-Female Lower Urinary
      Tract Symptoms short form (FLUTS-SF) while the short form of the International
      Index of Erectile Function (IIEF-5) showed the hardest readability. Based on the
      FKGL between 0% (FLUTS-SF) and 80% (IIEF-5) of the single-items were written
      above the recommended grade levels. Conclusions: The questionnaires that are used
      most frequently in urology mainly show a satisfactory overall readability.
      Inadequate readability levels were not only found for individual questionnaires
      but also for single-items of the majority of assessed questionnaires. This
      requires consideration for the interpretation of results and when developing
      novel health-related surveys.

PMID- 30182075
TI  - Predicting trifecta outcomes after robot-assisted nephron-sparing surgery: Beyond
      the nephrometry score.
AB  - Purpose: RENAL nephrometry score (RNS) was devised for deciding the approach for
      renal tumors. It is increasingly used in predicting perioperative outcomes with
      variable results. The actual difficulty encountered during surgery depends on a
      number of other variables. The main purpose of this prospective study was to
      identify these variables which are not addressed by current RNS. Materials and
      Methods: Forty-nine patients undergoing robotic nephron sparing surgery from
      January 2015 onward were included. RNS was calculated from the imaging. Operating
      surgeon rated each surgery on a Likert scale of 0-4 after the completion of the
      procedure. The questionnaire was pre-validated in 5 cases before administration.
      The correlation between the surgeon rating and RNS with perioperative parameters
      and trifecta outcomes were calculated. Results: Forty-seven percent surgeries
      were rated easy, and 53.0% were rated as difficult. Surgeries for hilar,
      posterior location and presence of supernumerary vessels were found to be the a
      cause of difficulty. Trifecta outcomes were achieved in 37/49 patients (75.5%).
      The mean rating was 2.580+/-0.900 in trifecta negative patients while it was
      1.410+/-0.832 in trifecta positive patient (p<0.0001). Surgeon's rating
      correlated positively with trifecta outcomes (likelihood ratio=15.75, p=0.006).
      Conclusions: The RNS remained a useful tool for determining renal tumor
      complexity. The intraoperative difficulty faced by the surgeon can be rated which
      can better predict perioperative trifecta outcomes. A useful predicting tool can
      be developed using the two parameters (RNS and surgeon rated difficulty).

PMID- 30182076
TI  - Changes in health-related quality of life after radical prostatectomy for
      prostate cancer: A longitudinal cohort study in Korea.
AB  - Purpose: To evaluate longitudinal changes in health-related quality of life and
      satisfaction after radical prostatectomy for the treatment of prostate cancer in
      Korean men. Materials and Methods: Data from patients with localized prostate
      cancer who underwent radical prostatectomy between January 2012 and December 2013
      were analyzed. Patients completed the Expanded Prostate Cancer Index Composite
      questionnaire at scheduled clinic visits (baseline and 1, 3, 6, and 12 months
      post-surgery). Results: Data from 211 men were evaluated. Urinary domain summary
      scores decreased postoperatively but improved over the 12-month follow-up period.
      Urinary function and incontinence had not recovered to baseline values at 12
      months, whereas urinary bother and irritation/obstruction scores showed no
      differences from baseline at 12 months. Sexual function improved at each
      timepoint to 12 months but did not recover to baseline values; sexual bother was
      approximately 50% of baseline values at 12 months. Recovery of sexual function
      was significantly greater in patients who underwent robotic surgery versus those
      who underwent open surgery. At the end of the study period, 66.3% of patients
      were satisfied with the treatment they had received; multivariate analysis showed
      that only urinary function recovery was significantly associated with overall
      satisfaction. Conclusions: Urinary outcomes and sexual outcomes had not returned
      to baseline at 12 months. Recovery of sexual function was significantly greater
      in patients who underwent robotic surgery. Only recovery of urinary function was
      significantly associated with overall satisfaction 12 months after radical
      prostatectomy in this cohort of Korean men.

PMID- 30182077
TI  - Unplanned 30-day readmission rates in patients undergoing endo-urological
      surgeries for upper urinary tract calculi.
AB  - Purpose: To see the 30-day unplanned readmission rates in patients underdoing
      endo-urological surgeries for upper urinary tract calculi we conducted this
      retrospective study at King George's Medical University, Lucknow, India.
      Unplanned readmissions not only add to healthcare costs but also are bothersome
      for the patients. There are many studies on 30-day unplanned readmissions in
      general surgical patients. Although similar studies have been done in certain
      urological procedures, no study has reported readmission rates or its risk
      factors in patients undergoing surgeries for upper urinary tract calculi.
      Materials and Methods: We retrospectively reviewed our prospectively maintained
      database from 1st January 2009 to 31st December 2017, for the patients who
      underwent endo-urological procedures for upper urinary tract calculi and
      identified the patients who were re-admitted within 30 days of discharge.
      Results: Out of the total 3,209 patients undergoing endo-urological procedures
      for upper urinary tract calculi 56 were re-admitted. The readmission rate was
      1.74% over the study period. The most common etiology for readmission was sepsis
      followed by hematuria. The significant risk factors for readmission in bivariate
      analysis included male gender, age >65 years, current smoking, chronic
      obstructive pulmonary disease, diabetes mellitus, bleeding disorder, prior
      cardiac disease, and American Society of Anesthesiologists (ASA) class >=3. In
      multivariate risk adjusted logistic regression analysis ASA class >=3 was the
      only independent risk factor for readmission. Conclusions: The readmission rates
      in endo-urological procedures for urolithiasis are less compared to other
      procedures. ASA class >=3 is the most important independent predictor of
      unplanned 30-day readmissions.

PMID- 30182078
TI  - In vitro, in vivo, and clinical tests of a novel flexible ureteroscope for the
      diagnosis and treatment of kidney and ureteral diseases.
AB  - Purpose: Despite advances in flexible ureteroscopy, the high cost and long repair
      time of ureteroscopes limit their use in the urology. We compared the performance
      of a novel flexible ureteroscope (fURS) 'HF-EH' with that of the two contemporary
      fURSs 'URF-P6' and 'COBRA'. Materials and Methods: We compared in vitro
      measurements of deflection angle, irrigation flow rate, and image quality between
      HF-EH and URF-P6 while also inspecting renal collecting systems in five female
      pigs. For clinical testing, we performed retrograde intrarenal surgeries using HF
      EH in four patients. Experienced urologists compared performance parameters
      (irrigation, convenience, and maneuverability) between the HF-EH and COBRA.
      Results: The flow rate of HF-EH (21.0 mL/min) was worse, and its resolution (1.59
      line pairs/mm) was inferior to that of URF-P6 (28.7 mL/min and 3.17 line
      pairs/mm, respectively). However, HF-EH was superior to URF-P6 in terms of loss
      of deflection angle with the insertion of accessories (1.8% vs. 12.7%). In vivo
      and clinical testing revealed that the performance parameters of HF-EH were
      slightly inferior to those of conventional domestic fURSs. We successfully
      performed retrograde intrarenal surgeries using HF-EH in four patients and
      achieved stone-free statuses in two. None of the patients exhibited any procedure
      related complications. Conclusions: Although we observed that two of the three
      performance parameters of the novel ureteroscope 'HF-EH' were inferior to those
      of the conventional ureteroscope, we successfully used HF-EH to perform
      retrograde intrarenal surgeries in patients. Further studies on performance and
      durability are warranted for making HF-EH commercially available.

PMID- 30182079
TI  - Clinical characteristics of postoperative febrile urinary tract infections after
      ureteroscopic lithotripsy.
AB  - Purpose: Ureteroscopic lithotripsy (URS) is gaining popularity for the management
      of ureteral stones and even renal stones, with high efficacy and minimal
      invasiveness. Although this procedure is known to be safe and to have a low
      complication rate, febrile urinary tract infection (UTI) after URS is not rare.
      Therefore, we aimed to analyze the risk factors and causative pathogens of
      febrile UTI after URS. Materials and Methods: Between January 2013 and June 2015,
      304 patients underwent URS for ureteral or renal stones. The rate of
      postoperative febrile UTI and the causative pathogens were verified, and the risk
      factors for postoperative febrile UTI were analyzed using logistic regression
      analysis. Results: Of 304 patients, postoperative febrile UTI occurred in 43
      patients (14.1%). Of them, pathogens were cultured in blood or urine in 19
      patients (44.2%), and definite pathogens were not identified in 24 patients
      (55.8%). In patients with an identified pathogen, Pseudomonas aeruginosa had the
      highest incidence. Multivariate analysis showed that the operation time (p<0.001)
      was an independent risk factor for febrile UTI after URS. The cut-off value of
      operation time for increased risk of febrile UTI was 70 minutes. Conclusions:
      Overall, febrile UTI after URS occurred in 14.1% of patients, and the operation
      time was an independent predictive factor for this complication. Considering that
      more than 83.7% of febrile UTIs after URS were not controlled with
      fluoroquinolones, it may be more appropriate to use higher-level antibiotics for
      treatment, even in cases with unidentified pathogens.

PMID- 30182080
TI  - Infection following penile prosthesis placement at an academic training center
      remains low despite involvement of surgeons-in-training.
AB  - Purpose: Primary care providers harbor misconceptions regarding penile prosthetic
      surgery, largely overestimating the rate of infection. Rates of infection
      following surgery for primary placement and revision are estimated as 1% to 3%
      and 10% to 18%, respectively. Our objective was to determine the contemporary
      incidence of infection following inflatable penile prostheses surgery at an
      academic training center where surgeons-in-training are routinely involved.
      Materials and Methods: Review of a prospectively collected single-surgeon
      database was performed. All cases of inflatable penile prostheses placement from
      January 2011 through June 2017 were reviewed. Information regarding training
      level of assistant surgeon(s) was collected, and follow-up data was compiled
      regarding postoperative infections and need for revision surgery. Results: Three
      hundred nine cases meeting inclusion criteria were identified. Mean patient age
      was 64.2 years, and mean follow-up was 28.7 months. Distribution involved 257
      (83.2%) for primary placement, 45 (14.6%) for removal/replacement, and 7 (2.3%)
      in setting of prior device removal. Diabetes was noted in 31.1% of men. Surgeon
      in-training involvement was noted in 100% of cases. Infection was confirmed in a
      patient who had skin breakdown over an area of corporal reconstruction with
      polytetrafluoroethylene. The overall postoperative infection rate was 0.3%.
      Conclusions: In this series from an academic training center, infection following
      penile prosthetic surgery is low, similar to other centers of excellence, even
      with 100% involvement of surgeons-in-training. This data should be used to better
      inform primary care providers and members of the general public potentially
      interested in restoration of sexual function.

PMID- 30182081
TI  - Real-time simultaneous endoscopic combined intrarenal surgery with intermediate
      supine position: Washout mechanism and transport technique.
AB  - Endoscopic combined intrarenal surgery (ECIRS) with simultaneous retrograde
      intrarenal surgery (RIRS) and percutaneous nephrolithotomy (PCNL) has been
      proposed as a new surgical treatment to overcome the disadvantage of RIRS and
      PCNL monotherapies in the treatment of renal stone. One of advantages of ECIRS is
      that it can increase stone-free rates in complex renal stone within single
      session. Intermediate-supine position in real-time simultaneous ECIRS can prevent
      an anesthesiologic problem, and patient's burden is small even for long-term
      operation. Thus, we will share the experience and advantages of real-time
      simultaneous ECIRS and introduce techniques to increase the stone-free rate.

PMID- 30182082
TI  - Usefulness and safety of a scissors-type knife in endoscopic submucosal
      dissection for nonampullary duodenal epithelial tumors.

PMID- 30182083
TI  - Endoscopic treatment of internal hemorrhoids by use of a bipolar system.

PMID- 30182084
TI  - Creating effective titles for your scientific publications.

PMID- 30182085
TI  - EUS-directed transgastric ERCP (EDGE) with use of a 20-mm * 10-mm lumen-apposing
      metal stent in a patient with Roux-en-Y gastric bypass.

PMID- 30182086
TI  - Gastric foreign body removal with a lithotriptor.

PMID- 30182087
TI  - Successful removal of duodenal submucosal tumors with endoscopic submucosal
      dissection.

PMID- 30182088
TI  - Successful 2-channel cold snare polypectomy of a colorectal lesion involving the
      appendiceal orifice.

PMID- 30182089
TI  - Novel forward-viewing EUS-guided ileoureterostomy technique for recurrent
      pyelonephritis caused by ureteral stenosis.

PMID- 30182090
TI  - Endoscopic drainage of pancreatic fluid collections by use of a novel biflanged
      stent with electrocautery-enhanced delivery system.

PMID- 30182091
TI  - The Value of an Automated Ultrasound System in the Detection of Synovitis.
AB  - Background: The detection of joint swelling caused by synovitis is important for
      the diagnosis of inflammatory arthritis. Ultrasound (US) and MRI have proven to
      be more sensitive and reliable than physical examination, but they are time
      consuming and expensive. The automated breast volume scanner was developed to
      acquire serial B-mode pictures of the female breast and these can be analyzed in
      all three dimensions. Objectives: To analyze the value of automated B-mode
      ultrasound employing the ABVS system in detecting synovitis of the finger joints
      compared to manual ultrasound (mUS) and physical examination, using MRI as the
      gold standard. Methods: 19 consecutive patients suffering from active rheumatoid
      (n=15) or psoriatic (n=4) arthritis were included. Automated and mUS were
      conducted with a linear array (ACUSON S2000TM, 11 MHz). Multiplanar
      reconstruction enabled examination of the images for the presence of synovitis.
      Results: 90% of the hand joints were assessable by automated ultrasound.
      Automated US detected 12.0, mUS 14.2, MRI 13.4, and clinical examination 4.1
      positive joints - i. e. joints with synovitis - on average per patient. The inter
      observer reliability of both assessors for automated and mUS, MRI, and physical
      examination, was 66.9%, 72.7%, 95.1%, and 88.9%, respectively. 84.3% of the
      joints classified as positive on MRI were confirmed by automated ultrasound,
      85.5% on mUS, and 36.0 on physical examination. This translated into a
      sensitivity of 83.5%, 85.5%, and 36.0% for the three methods, respectively.
      Conclusion: Automated ultrasound is a promising ultrasound method for assessing
      small joints in patients with inflammatory arthritis.

PMID- 30182092
TI  - Optimal use of meningococcal serogroup B vaccines: moving beyond outbreak
      control.
AB  - Neisseria meningitidis is a major cause of meningitis and septicemia globally.
      Vaccines directed against N. meningitidis serogroup B (MenB) have been used to
      control sporadic and sustained disease in industrialized and non-industrialized
      countries. Early outer membrane vesicle (OMV) vaccines effectively reduced MenB
      disease in countries such as Norway, New Zealand, and France; however, these
      vaccines were highly specific for their targeted outbreak strain, did not elicit
      a durable immune response, and were ineffective for widespread use due to the
      diversity of MenB-disease-causing isolates. Recently developed recombinant
      protein-based MenB vaccines that target conserved surface proteins have the
      potential to induce a broader immune response against the diversity of disease
      causing strains. Given the deleterious consequences and sporadic nature of MenB
      disease, the use of optimal vaccination strategies is crucial for prevention.
      Reactive vaccination strategies used in the past have significant limitations,
      including delayed implementation, substantial use of resources, and time
      constraints. The broad coverage potential of recombinant protein-based MenB
      vaccines suggests that routine use could result in a reduced burden of disease.
      Despite this, routine use of MenB vaccines is currently limited in practice.

PMID- 30182093
TI  - Increasing time on target: utilization of inhibitors of cysteine cathepsins to
      enhance the tumor retention of receptor-targeted agents.
AB  - We report a strategy of utilizing irreversible cysteine cathepsin inhibitor as
      trapping agent to increase the tumor residence time of receptor-targeted agents.
      The targeted constructs incorporating these cysteine cathepsin trapping agents
      were able to form high molecular weight adducts with intracellular cysteine
      cathepsins, thus achieving superior retention in tumor tissues.

PMID- 30182094
TI  - Selective aerobic oxidation of halides and amines with an inorganic-ligand
      supported zinc catalyst.
AB  - A practical, efficient and environmentally benign catalytic protocol for the
      oxidative cross-coupling reaction of halides with amines, oxidative self-coupling
      of amines and oxidation of halides was developed with inorganic-ligand supported
      ZnPOM (NH4)4[ZnMo6O18(OH)6] using molecular oxygen. This method mainly utilizes
      an inorganic polymolybdate ligand to support the Zn2+ ion, avoiding the use of
      complicated organic ligands.

PMID- 30182095
TI  - Tuning the conductance of a molecular wire by the interplay of donor and acceptor
      units.
AB  - We investigate the conductance of optimized donor-acceptor-donor molecular wires
      obtained by on-surface synthesis on the Au(111) surface. A careful balance
      between acceptors and donors is achieved using a diketopyrrolopyrrole acceptor
      and two thiophene donors per unit along the wire. Scanning tunneling microscopy
      imaging, spectroscopy, and conductance measurements done by pulling a single
      molecular wire at one end are presented. We show that the conductance of the
      obtained wires is among the highest reported so far in a tunneling transport
      regime, with an inverse decay length of 0.17 A-1. Using complex band structure
      calculations, different donor and acceptor groups are discussed, showing how a
      balanced combination of donor and acceptor units along the wire can further
      minimize the decay of the tunneling current with length.

PMID- 30182096
TI  - Visible-light photoexcitation of pyridine surface complex, leading to selective
      dehydrogenative cross-coupling with cyclohexane.
AB  - Upon photoirradiation with visible light, a pyridine molecule adsorbed on a TiO2
      surface can be photoexcited to give a pyridine radical cation via ligand-to-metal
      charge transfer (LMCT) between pyridine and titanium. This leads to
      dehydrogenative cross-coupling (DCC) between pyridine and cyclohexane with
      concomitant hydrogen evolution. Since the radical cation can selectively oxidize
      cyclohexane to a cyclohexyl radical, the cross-coupling between pyridine and
      cyclohexane proceeds with higher selectivity compared with that in photocatalysis
      by TiO2 under UV irradiation.

PMID- 30182097
TI  - Superhydrophobic plasmonic nanoarchitectures based on aluminum hydroxide
      nanotemplates.
AB  - The combined characteristics of non-wettabililty and strong plasmonic resonances
      make superhydrophobic plasmonic nanostructures an appealing tool for
      ultrasensitive detection in surface-enhanced Raman scattering (SERS). However,
      inducing superhydrophobic surfaces on originally hydrophilic metals (e.g., gold,
      silver) while achieving high plasmonic enhancement requires sophisticated surface
      engineering and often involves complex fabrication processes. In this article, we
      design and fabricate cost effective and scalable plasmonic nanostructures with
      both superhydrophobicity (a water contact angle >160 degrees ) and high SERS
      signal (enhancement factor ~106). Silver-coated aluminum hydroxide nanotemplates
      are obtained from a simple wet process, followed by thermal evaporation of silver
      nanoparticles. We find that the largest SERS enhancement is obtained when the
      contact angle is maximum. This confirms that the control of surface wettability
      is an effective way to improve detection sensitivity in SERS measurements. The
      nanotemplates developed in this study could be applied further in various
      applications, including microfluidic biomolecular optical sensors,
      photocatalysts, and optoelectronic devices.

PMID- 30182098
TI  - Organic amines as templates: pore imprints with exactly matching sizes in a
      series of metal-organic frameworks.
AB  - Three kinds of organic amines have been used as soft templates for constructing a
      series of metal-organic frameworks with variable pores. The pore sizes of these
      MOFs exactly matched those of amines, confirming the template effect of these
      amines.

PMID- 30182099
TI  - Building better rechargeable Zn-Mn batteries with a highly active Mn3O4/carbon
      nanowire cathode and neutral Na2SO4/MnSO4 electrolyte.
AB  - A more reliable/eco-friendly secondary Zn-Mn battery system is built with highly
      active Mn3O4@carbon nanowires and near-neutral electrolytes. Such configured
      batteries show high reversibility and superior behavior in terms of both stored
      capacity and cycling durability, holding great promise in near-future power
      supply applications.

PMID- 30182100
TI  - The evaporation kinetics of pure water droplets at varying drying rates and the
      use of evaporation rates to infer the gas phase relative humidity.
AB  - Numerous analytical models have been applied to describe the
      evaporation/condensation kinetics of volatile components from aerosol particles
      for use in many applications. However, the applicability of these models for
      treating cases that lead to substantial and rapid changes in particle temperature
      due to, for example, evaporative cooling remain to be compared with measurements.
      We consider three typical treatments, comparing predictions of the evaporation
      rates of pure water droplets over a wide range in gas phase relative humidity
      (RH) and exploring the sensitivity of the predictions to uncertainties in the
      thermophysical gas and condensed-phase parameters. We also compare predictions
      from the three treatments to measurements of the evaporation rates of pure water
      droplets with varying RH using an electrodynamic balance (EDB), concluding that
      only two of the model treatments are sufficiently able to account for the level
      of evaporative cooling (typically as high as 12 K). Finally, we show that the RH
      can be inferred accurately from the evaporation rate of pure water droplets over
      the full range in accessible RH and comparison with the model predictions (within
      absolute uncertainties of 2.5% RH over the range 20% to 95% RH), considering the
      level of agreement with independent measurements made through determining the
      equilibrated size of aqueous sodium chloride and sodium nitrate droplets.

PMID- 30182101
TI  - Dynamics of breaking intermolecular bonds in high-speed force spectroscopy.
AB  - Atomic force microscope based single-molecule force spectroscopy provides a
      description of a variety of intermolecular interactions such as those occurring
      between receptor molecules and their ligands. Advances in force spectroscopy have
      enabled performing measurements at high-speeds and sub-microsecond resolutions.
      We report experiments performed on a biotin-avidin system that reveal that the
      measured force decreases with the loading rate at high rates. This result is at
      odds with the established Bell-Evans theory that predicts a monotonic increase of
      the rupture force with the loading rate. We demonstrate that inertial and
      hydrodynamic forces generated during the breaking of the bond dominate the
      measured force at high loading rates. We develop a correction factor to
      incorporate those effects into the Bell-Evans theory. The correction is necessary
      to obtain accurate values of the intermolecular forces at high speeds.

PMID- 30182102
TI  - Mitochondria: promising organelle targets for cancer diagnosis and treatment.
AB  - Mitochondria, the energy supply factories for cell-life activities, play
      important roles in controlling epigenetics, differentiation and initiation, and
      the execution of apoptosis. These functions of the mitochondria contribute to
      cell adaptation to challenging microenvironment conditions. In past decades,
      mitochondrial malfunction has been revealed to be closely related to the
      occurrence and development of a variety of human disorders, including cancer and
      multiple neurodegenerative diseases. The disturbance of the mitochondrial genome
      (mtDNA) or mitochondrial vital functions, e.g., the production of adenosine
      triphosphate (ATP) and the generation of reactive oxygen species (ROS), can
      potentially be involved in disease pathogenesis. Recent research has shown that
      the precise monitoring of mitochondrial environments can provide potential
      directions for cancer diagnosis. Furthermore, mitochondrial-targeted cancer
      treatment exhibits unparalleled superiority for enhanced tumor therapy.
      Therefore, in this review, we focus on mitochondrial-based cancer diagnosis via
      monitoring mitochondrial respiration or mitophagy. Current approaches using
      mitochondrial-based cancer treatments, including targeting mitochondrial ATP,
      mitochondrial membrane permeability, and mitochondrial ROS levels and mtDNA, are
      also summarized. This review will provide insights into mitochondrial-mediated
      tumor monitoring and mitochondrial-based therapy.

PMID- 30182103
TI  - Chimonanthus nitens Oliv. leaf extract exerting anti-hyperglycemic activity by
      modulating GLUT4 and GLUT1 in the skeletal muscle of a diabetic mouse model.
AB  - The present study aimed to explore the potent molecular mechanisms behind the
      hypoglycemic effect of Chimonanthus nitens Oliv. leaf extract (COE) in
      combination with a high-glucose-fat diet-fed and streptozotocin-induced diabetic
      mouse model. COE (50 and 200 mg per kg body weight per day) was given to the
      diabetic-model mice by intragastric administration for 4 weeks. It was found that
      the fasting blood glucose level (FBG), serum insulin level (FINS), and insulin
      sensitivity index (ISI) were significantly improved in the COE-treated diabetic
      model mice. Glucose metabolism genes expression analysis of the skeletal muscle
      showed that COE exerted a glucose-lowering effect through the following two ways:
      on the one hand, COE enhanced insulin sensitivity by upregulating the
      transcription level of GLUT4, and in addition, it enhanced the insulin signaling
      pathway to promote the translocation of GLUT4 and upregulated thermogenesis genes
      expression, including PGC-1alpha and UCP-1; while on the other hand, GLUT1
      expression was also increased in both the transcription and translation levels in
      the presence of COE. These two ways may result in promoting glucose uptake in
      skeletal muscle, thus leading to the reduction of the blood glucose level. The
      results suggested that COE ameliorated hyperglycemia in the diabetic-model mice
      through regulating glucose transporters, and then was likely to increase glucose
      uptake, which provided more evidence for applying COE to treat anti
      hyperglycemia.

PMID- 30182104
TI  - Steric effects determine the mechanisms of reactions between bis(N-heterocyclic
      carbene)-nickel(0) complexes and aryl halides.
AB  - Computational investigations of the reactions of [Ni(NHC)2] complexes with aryl
      halides show that the outcomes are governed by the steric impact of the ligand
      (NHC = N-heterocyclic carbene). Small ligands permit facile oxidative addition,
      leading to NiII complexes, while larger NHC ligands prevent coordination of the
      aryl halide and favour the halide abstraction to form NiI.

PMID- 30182105
TI  - Effect of thiophene substitution on the intersystem crossing of arene
      photosensitizers.
AB  - The effect of thienyl substitution on the intersystem crossing (ISC) of a few
      arenes was studied using steady state and time-resolved transient absorption and
      emission spectroscopies, as well as DFT/TDDFT computations. We found that the
      phenyl and thienyl substituents generally induce red-shifted absorptions for the
      chromophores, and the DFT/TDDFT computations show that the red-shifted absorption
      and emission are due to the increased HOMO and the reduced LUMO energy levels.
      Nanosecond transient absorption spectra indicate the formation of a triplet
      state, the triplet state lifetime is up to 282 MUs, and the singlet oxygen
      quantum yields (PhiDelta) are up to 60%. DFT/TDDFT computations indicate that
      introducing the thienyl substituent alters the relative singlet/triplet excited
      state energy levels, and the energy level-matched S1/T2 states are responsible
      for the enhanced ISC of the thienyl compounds. This information is useful for the
      design of heavy atom-free triplet photosensitizers and for the study of the
      fundamental photochemistry of organic compounds.

PMID- 30182106
TI  - Treatment of neurodegenerative disorders through the blood-brain barrier using
      nanocarriers.
AB  - Neurodegenerative diseases refer to disorders of the central nervous system (CNS)
      that are caused by neuronal degradations, dysfunctions, or death. Alzheimer's
      disease, Parkinson's disease, and Huntington's disease (APHD) are regarded as the
      three major neurodegenerative diseases. There is a vast body of literature on the
      causes and treatments of these neurodegenerative diseases. However, the main
      obstacle in developing an effective treatment strategy is the permeability of the
      treatment components at the blood-brain barrier (BBB). Several strategies have
      been developed to improve this obstruction. For example, nanomaterials facilitate
      drug delivery to the BBB due to their size. They have been used widely in
      nanomedicine and as nanoprobes for diagnosis purposes among others in
      neuroscience. Nanomaterials in different forms, such as nanoparticles,
      nanoemulsions, solid lipid nanoparticles (SLN), and liposomes, have been used to
      treat neurodegenerative diseases. This review will cover the basic concepts and
      applications of nanomaterials in the therapy of APHD.

PMID- 30182107
TI  - Enhancing the blinking fluorescence of single-molecule localization imaging by
      using a surface-plasmon-polariton-enhanced substrate.
AB  - Super-resolution imaging based on single-molecule localization microscopy
      combined with the surface plasmon polariton (SPP)-enhanced fluorescence of
      spontaneously blinking fluorophores was demonstrated to visualize the nanoscale
      level positioning information of cell-adhesion-associated proteins. Glass
      substrates with a deposited silver layer were utilized to induce a SPP-enhanced
      field on the silver surface and significantly strengthen the fluorescence signals
      of the fluorophores by more than 300%. The illumination power density for
      localization imaging at a spatial resolution of 25 +/- 11 nm was 31.6 W cm-2.
      This low illumination power density will facilitate the reduction of
      phototoxicity of the biospecimens for single-molecule localization imaging. The
      proposed strategy provides a uniform distribution of the SPP-enhanced field on
      the silver surface, enabling visualization of the spatial distribution of labeled
      proteins without interference caused by the enhanced field distribution.

PMID- 30182108
TI  - Enantioselective synthesis of axially chiral vinyl arenes through palladium
      catalyzed C-H olefination.
AB  - A palladium-catalyzed ketoxime-chelation-assisted enantioselective C-H
      olefination of 2-arylcyclohex-2-enone oxime ether with a wide range of olefins as
      coupling partners was developed. Employing ketoxime ether as an efficient
      directing group, a variety of axially chiral vinyl arenes was synthesized by
      Pd(ii)-catalyzed C-H functionalization with excellent enantioselectivities (96 ->
      99% ee) under mild conditions.

PMID- 30182109
TI  - Phase separation and selective guest-host binding in multi-component
      supramolecular self-assembly on Au(111).
AB  - Bi-component supramolecular self-assembly of trimesic acid and benzenetribenzoic
      acid on Au(111) results in phase-separated mono-component porous structures. The
      pores of the two structures exhibit high selectivity in the binding of coronene
      molecules.

PMID- 30182110
TI  - Mechanistic view of Ru-catalyzed C-H bond activation and functionalization:
      computational advances.
AB  - Ru-Catalyzed aromatic C-H bond activation and functionalization have emerged as
      important topics because they have resulted in remarkable progress in organic
      synthesis. Both experimental and theoretical studies of their mechanisms are
      important for the design of new synthetic methodologies. In this review, a
      mechanistic view of the Ru-mediated C-H bond cleavage step is first given to
      reveal the C-H bond activation modes, including oxidative addition, metathesis
      and base-assisted deprotonation. In this process, directing groups play an
      important role in determining the reactivity of the C-H bond. The C-H bond
      activation generally leads to the formation of a Ru-C bond, which is further
      functionalized in the subsequent steps. The mechanisms of Ru-catalyzed arylation,
      alkylation, and alkenylation of arenes are summarized, and these transformations
      can be categorized into cross-coupling with electrophiles or oxidative coupling
      with nucleophiles. In addition, the mechanism of ortho-ruthenation-enabled remote
      C-H bond functionalization is also discussed.

PMID- 30182111
TI  - Unconventional locomotion of liquid metal droplets driven by magnetic fields.
AB  - The locomotion of liquid metal droplets enables enormous potential for realizing
      various applications in microelectromechanical systems (MEMSs), biomimetics, and
      microfluidics. However, current techniques for actuating liquid metal droplets
      are either associated with intense electrochemical reactions or require
      modification of their physical properties by coating/mixing them with other
      materials. These methods either generate gas bubbles or compromise the stability
      and liquidity of the liquid metal. Here, we introduce an innovative method for
      controlling the locomotion of liquid metal droplets using Lorentz force induced
      by magnetic fields. Remarkably, utilizing a magnetic field to induce actuation
      avoids the generation of gas bubbles in comparison to the method of forming a
      surface tension gradient on the liquid metal using electrochemistry. In addition,
      the use of Lorentz force avoids the need of mixing liquid metals with
      ferromagnetic materials, which may compromise the liquidity of liquid metals.
      Most importantly, we discover that the existence of a slip layer for liquid metal
      droplets distinguishes their actuation behaviors from solid metallic spheres. We
      investigate the parameters affecting the actuation behavior of liquid metal
      droplets and explore the science behind its operation. We further conducted a
      series of proof-of-concept experiments to verify the controllability of our
      method for actuating liquid metal droplets. As such, we believe that the
      presented technique represents a significant advance in comparison to reported
      actuation methods for liquid metals, and possesses the potential to be readily
      adapted by other systems to advance the fields of MEMS actuation and soft
      robotics.

PMID- 30182112
TI  - Real-time characterization of negative air ion-induced decomposition of indoor
      organic contaminants by mass spectrometry.
AB  - This study describes an integrated system consisting of a negative air ion (NAI)
      generator, an indoor organic contaminant (IOC) sprayer, and mass spectrometry
      (MS), allowing for the real-time probing of reactions between NAIs and IOCs and
      could be extended to investigate a wide range of interactions between negative
      ions and chemical compounds.

PMID- 30182113
TI  - Effect of lactoferrin on taste and smell abnormalities induced by chemotherapy: a
      proteome analysis.
AB  - Cancer patients receiving chemotherapy often experience taste and smell
      abnormalities (TSA). To date, the underlying molecular mechanisms of this
      frequent side-effect have not been determined and effective treatments are not
      available. This study assessed the feasibility of lactoferrin (LF)
      supplementation as a treatment for TSA and investigate the related mechanisms
      through salivary proteome analysis. Nineteen cancer patients with established TSA
      following chemotherapy administration were enrolled in this study. Cancer
      patients and additional 12 healthy subjects took LF supplements, 3 tablets per
      day (250 mg per tablet), for 30 days. Saliva was collected at three timepoints:
      baseline, 30-day LF supplementation, and 30-day post-LF supplementation.
      Patient's TSA level, salivary proteome, and salivary minerals at each LF
      treatment stage were analyzed. High TSA level was associated with high
      concentration of salivary Fe and loss of critical salivary immune proteins. LF
      supplementation significantly decreased the concentration of salivary Fe (P =
      0.025), increased the abundance (P < 0.05) of salivary alpha-amylase and Zn-alpha
      2-GP, and led to an overall increase of expression (>=2-fold changes) of immune
      proteins including immunoglobulin heavy chain, annexin A1, and proteinase
      inhibitor. Abundance of alpha-amylase and SPLUNC2 were further increased (P <
      0.05) at 30-day post-LF supplementation in cancer patients. At the same time,
      total TSA score was significantly reduced (P < 0.001) in chemotherapy patients.
      This study demonstrated the feasibility of developing lactoferrin supplementation
      as a treatment to reduce TSA caused by chemotherapy and improve cancer patient's
      oral immunity.

PMID- 30182114
TI  - Palladium-catalyzed aerobic oxidative carbonylation of alkynes with amines: a
      general access to substituted maleimides.
AB  - A catalytic oxidative carbonylation reaction was developed for the synthesis of
      polysubstituted maleimides from alkynes and amines with air as a green oxidant.
      This novel transformation proceeds in the presence of palladium chloride without
      the need for expensive ligands or additives and has a broad substrate scope
      affording a variety of maleimides in good to high yields.

PMID- 30182115
TI  - Tuning the biomimetic performances of 4-hydroxyproline-containing cyclic
      peptoids.
AB  - Five new cyclic peptoids containing (2S,4R)-4-hydroxyproline (Hyp) residues have
      been designed and synthesized using a mixed "submonomer/monomer" approach. Alkali
      metal cation affinities and ion transport activities were assessed by
      experimental (NMR and HPTS assay in liposomes) and computational methods. Easy
      functionalization of hydroxyproline residues afforded a bouquet of cyclic
      oligomers showing correlation between ion transport abilities and cytotoxic
      activities on selected human cancer cell lines.

PMID- 30182116
TI  - Synthesis of indole-fused heteroacenes by cascade cyclisation involving
      rhodium(ii)-catalysed intramolecular C-H amination.
AB  - Heteroacenes are potentially important materials for organic electronics and
      their syntheses are of topical interest. Herein we report the development of a
      catalytic, redox-neutral reaction for the synthesis of the 5,10-dihydroindolo[3,2
      b]indole class of heteroacenes. 2-[(2-Azidophenyl)ethynyl]anilines undergo
      cascade cyclisation by gold(i)/rhodium(ii) relay catalysis. Control experiments
      show that gold(i) is an effective catalyst for the first indole cyclisation with
      the aniline moiety, while the second cyclisation, which involves the azide
      moiety, is catalysed by rhodium(ii). This protocol delivers a variety of N
      substituted N'-unsubstituted dihydroindoloindoles. 2-[(2
      Azidophenyl)ethynyl]phenols are also converted into 10H-benzofuro[3,2-b]indoles
      through base-promoted benzofuran cyclisation followed by rhodium(ii)-catalysed C
      H amination. A related cascade cyclisation reaction of a 2-[(2
      azidophenyl)ethynyl]biphenyl is also reported.

PMID- 30182117
TI  - Spiral Eu(iii) coordination polymers with circularly polarized luminescence.
AB  - A spiral-type chiral Eu(iii) coordination polymer showed strong luminescence
      (emission quantum yield Phif-f = 57% and photosensitized energy transfer
      efficiency etasens = 53%) and effective CD and CPL properties (gCPL = 0.17) when
      compared with a mono-nuclear chiral Eu(iii) complex in the solid state (Phif-f =
      36%, etasens = 14%, and gCPL = 0.09).

PMID- 30182118
TI  - Electron correlation effects of the ThO and ThS molecules in the spinor basis. A
      relativistic coupled cluster study of ground and excited states properties.
AB  - We present a comprehensive relativistic coupled cluster study of the electronic
      structures of the ThO and ThS molecules in the spinor basis. Specifically, we use
      the single-reference coupled cluster and the multi-reference Fock Space Coupled
      Cluster (FSCC) methods to model their ground and electronically-excited states.
      Two variants of the FSCC method have been investigated: (a) one where the
      electronic spectrum is obtained from sector (1,1) of the Fock space, and (b)
      another where the excited states come from the doubly attached electronic states
      to the doubly charged systems (ThO2+ and ThS2+), that is, from sector (0,2) of
      the Fock space. Our study provides a reliable set of spectroscopic parameters
      such as bond lengths, excitation energies, and vibrational frequencies, as well
      as a detailed analysis of the electron correlation effects in the ThO and ThS
      molecules. Finally, we examine the first ionization potential and electron
      affinity of the above mentioned molecules.

PMID- 30182119
TI  - A cluster size distribution theory to study the thermodynamics and phase behavior
      of multi-bonding single site solutes in patchy colloidal mixtures.
AB  - We study binary mixtures of multi-bonding single site solute particles in a
      solvent comprising patchy colloid particles. The particles in the mixture
      interact by very short-ranged attraction and hard-sphere repulsion. The
      attractive patch on the solute can bond with multiple solvent particles, whereas
      the patch on the solvent is restricted to bond only once. From a quasi-chemical
      analysis of association, in the hard-sphere reference we develop an accurate
      multi-body correlation information for the distribution of solvent particles over
      the patch region of the solute. We use this information within Wertheim's multi
      density formalism to develop a cluster size distribution theory that is capable
      of capturing the physics of multi-body association for any geometry of
      association sites on the solute. We use this general framework to study a mixture
      containing Janus solutes and one- or two-patch solvent particles over a range of
      concentration of the solute and association strengths. We find that a mixture of
      two-patch solvent (with both patches of the same kind) and multi-bonding solutes
      with different patch geometries can have a vapor-liquid equilibrium, although the
      pure components themselves cannot phase separate. The liquid state occurs at very
      low densities, forming a so-called empty liquid. For the relative association
      strengths studied in this work, we observe that the vapor-liquid coexistence
      curve broadens as the concentration of the patchy solvent particles in the liquid
      phase is increased. The pressure-composition phase equilibrium curves show
      negative azeotropes for these mixtures. We also observe that, for these mixtures,
      as the size of the patch on the solute particles is decreased, the critical
      temperature and the critical packing fraction decreases.

PMID- 30182120
TI  - Thermoelectrochemical cells based on Li+/Li redox couples in LiFSI glyme
      electrolytes.
AB  - Thermoelectrochemical cells (TECs) provide conspicuous advantages, including a
      high Seebeck coefficient (Se), design flexibility, and low cost compared with
      conventional thermoelectric devices. Here, we investigated TECs employing Li
      metal electrodes (Li-TECs) and a series of glyme (CH3O[CH2CH2O]nCH3, n = 1-4, nG)
      solvents with 0.5-3.0 M lithium-imide salts (lithium bis [fluorosulfonyl]imide,
      LiFSI, and lithium bis[trifluoromethane sulfonyl]imide, LiTFSI). The Se value and
      power performance of Li-TECs markedly depend on the nature of glyme solvents and
      Li salt concentration. The dependency of Se on the solvation structure of the Li
      ions is examined via Raman measurements, and the internal resistance of Li-TECs
      is analyzed using electrochemical impedance spectroscopy. Notably, a Li-TEC with
      1.0 M LiFSI 1G displays about two times higher power density and about eight
      times higher conversion efficiency than a conventional Cu-TEC utilizing aqueous
      electrolytes, which is ascribed to the high Se value and low thermal conductivity
      of the former. In addition, for a Li-TEC with 1.0 M LiFSI 1G, the low-temperature
      performance is examined to assess its practical feasibility.

PMID- 30182121
TI  - Designed multifunctional polymeric nanomedicines: long-term biodistribution and
      tumour accumulation of aptamer-targeted nanomaterials.
AB  - We report a novel multifunctional hyperbranched polymer based on polyethylene
      glycol (PEG) as a nanomedicine platform that facilitates longitudinal and
      quantitative 89Zr-PET imaging, enhancing knowledge of nanomaterial
      biodistribution and pharmacokinetics/pharmacodynamics both in vivo and ex vivo.
      Anti-VEGF-A DNA aptamer functionalization increased tumour accumulation by >2
      fold in a breast cancer model.

PMID- 30182122
TI  - Interaction of nanodiamonds with bacteria.
AB  - Nanocarbons come in many forms and among their applications is the engineering of
      biocompatible and antibacterial materials. Studies have shown that diamond
      nanoparticles might have the interesting combination of both properties: they are
      highly biocompatible, while surprisingly reducing bacterial viability or growth
      at the same time. In this article, we consider for the first time the interaction
      of milled HPHT nanodiamonds with bacteria. These nanoparticles are capable of
      hosting nitrogen-vacancy (NV) centers, which provide stable fluorescence with
      potential use in sensing applications. An initial study was performed to assess
      the interaction of partially oxidized monocrystalline nanodiamonds with Gram
      positive S. aureus ATCC 12600 and Gram negative E. coli ATCC 8739. It was shown
      that for S. aureus ATCC 12600, the presence of these nanodiamonds leads to a
      sharp reduction of colony forming ability under optimal conditions. A different
      effect was observed on Gram negative E. coli ATCC 8739, where no significant
      adverse effects of ND presence was observed. The mode of interaction was further
      studied by electron microscopy and confocal microscopy. The effects of NDs on S.
      aureus viability were found to depend on many factors, including the
      concentration and size of nanoparticles, the suspension medium and incubation
      time.

PMID- 30182123
TI  - The electronic structure and stability of germanium tubes Ge30H12 and Ge33H12.
AB  - The geometries of non-tetrahedral and ultrastable silicon and germanium
      nanocrystals X18H12 and X19H12 (X = Si, Ge) have recently been predicted for the
      development of cluster-based nanomaterials for energy and microengineering
      purposes. To further explore the possibility of larger Ge clusters, we
      investigated in this work the molecular and electronic structure of the germanium
      tube Ge30H12, composed of six parallel, planar hexagons using DFT calculations.
      Insertion of Ge atoms at the center of three inner hexagons of Ge30H12 leads to a
      Ge33H12 tube, which is also an energy minimum structure. The electronic structure
      and molecular orbital shapes of these tubes can be predicted by the wavefunctions
      of a particle on a hollow cylinder model and a cylinder model. Different
      aromaticity indices including PDI, Iring, ING, MCI, and INB, as well as the
      electron localization function (ELF) were calculated to evaluate the electron
      delocalization and the aromaticity of the Ge tubes considered.

PMID- 30182124
TI  - DNA nanoflower blooms in nanochannels: a new strategy for miRNA detection.
AB  - By employing DNA nanoflower blooming in the nanochannels of porous anodic alumina
      (PAA), a nanochannel platform for microRNA (miRNA) detection has been proposed.
      Significant steric and electrostatic hindrance of the miRNA-initiated DNA
      nanoflower growth may also amplify the signal readout for miRNA detection to give
      excellent sensitivity, selectivity and reproducibility.

PMID- 30182125
TI  - Rotationally resolved electronic spectroscopy of 3-cyanoindole and the 3
      cyanoindole-water complex.
AB  - The rotationally resolved electronic spectra of the origin bands of 3
      cyanoindole, 3-cyanoindole(d1), and the 3-cyanoindole-(H2O)1 cluster have been
      measured and analyzed using evolutionary algorithms. For the monomer, permanent
      dipole moments of 5.90 D for the ground state, and of 5.35 D for the lowest
      excited singlet state have been obtained from electronic Stark spectroscopy. The
      orientation of the transition dipole moment is that of an 1Lb state for the
      monomer. The water moiety in the water cluster could be determined to be trans
      linearly bound to the NH group of 3-cyanoindole, with an NHO hydrogen bond length
      of 201.9 pm in the electronic ground state. Like the 3-cyanoindole monomer, the 3
      cyanoindole-water cluster also shows an 1Lb-like excited singlet state. The
      excited state lifetime of isolate 3-cyanoindole in the gas phase has been
      determined to be 9.8 ns, and that of 3-cyanoindole(d1) has been found to be 14.8
      ns, while that of the 1 : 1 water cluster is considerably shorter (3.6 ns). The
      excited state lifetime of 3-cyanoindole(d1) in D2O solution has been found to be
      smaller than 20 ps.

PMID- 30182126
TI  - Bistable [2]rotaxane encoding an orthogonally tunable fluorescent molecular
      system including white-light emission.
AB  - Orthogonally tunable multicolor fluorescence including white-light emission was
      achieved using a dual-component molecular system. Under external acid/base
      stimuli, we were able to change the fluorescence of a mixture of two fluorescent
      molecular switches in an orthogonal and reversible manner, hence generate
      emission of multiple colors from blue to yellow, including white light (CIE
      (0.29, 0.34)).

PMID- 30182127
TI  - Need for Further Analysis in Cognitive Outcomes of Children Born Preterm-Reply.

PMID- 30182128
TI  - Interview Functional Independence Measure score: self-reporting as a simpler
      alternative to multidisciplinary functional assessment.
AB  - INTRODUCTION: The Functional Independence Measure (FIM) is a validated, objective
      assessment of functional status. Though widely used in rehabilitation centres, it
      may not be practical for all patients due to time and/or personnel constraints.
      Studies show positive and negative agreements on self-reported FIM scores for
      patients with spinal cord injuries and amputees. We tested the validity of the
      self-reported FIM motor score among stroke patients. METHODS: In a prospective,
      double-blinded comparative study of patient self-reporting against
      multidisciplinary assessment, using the standard FIM algorithm, all eligible
      stroke patients (n = 47) admitted to our rehabilitation centre were included.
      Only 33 patients were included in the final analysis. RESULTS: There was
      substantial agreement for overall FIM motor score between patient self-reporting
      and multidisciplinary assessment (intraclass correlation [ICC] 0.651; 95%
      confidence interval 0.404-0.811). The scores of individual motor items also
      showed fair-to-good agreement (ICC range 0.431-0.618), except for eating,
      grooming, bathing and dressing of lower body (ICC < 0.400). CONCLUSION: There was
      no FIM assessment for 14 (29.8%) patients, which highlighted the need for
      alternative assessment tools. Discrepancies in some scores could be due to
      ignorance among patients about their own limitations or feelings of embarrassment
      about reporting. Our results may not be valid for patient populations with
      cognitive or communication deficits. However, a modest agreement between patient
      self-reporting and multidisciplinary assessment of FIM motor score was
      demonstrated. Though patients tend to overrate their performance, self-reported
      FIM motor score could be an alternative in situations where multidisciplinary FIM
      assessment may be difficult.

PMID- 30182129
TI  - Local experience with radiosurgery for vestibular schwannomas and recommendations
      for management.
AB  - INTRODUCTION: There are many treatment options for vestibular schwannomas (VSs),
      including radiosurgery. Previous studies have shown good outcomes for smaller
      tumours. We report the results of a seven-year cohort of patients with VS who
      were treated at our centre using a linear accelerator-based stereotactic
      radiosurgery system. METHODS: We retrospectively reviewed the case notes and
      magnetic resonance (MR) images of patients with VS treated with radiosurgery.
      Treatment was administered as either a single 13 Gy session or 25 Gy in five
      sessions. At our centre, only larger or higher Koos grade VSs, were routinely
      treated with hypofractionated radiosurgery. Tumour response and hearing were
      assessed using RECIST criteria and Gardner-Robertson scale, respectively. Other
      toxicities were assessed using physical examination and history-taking. Freedom
      from radiological progression was estimated with the Kaplan-Meier method.
      RESULTS: 46 patients received single-fraction radiosurgery and 31 received
      hypofractionated radiosurgery. Median follow-up duration was 40.6 months. 29
      patients had prior surgery to remove the tumour (median size 1.68 cm3). One
      patient who had symptomatic increase in tumour size (> 20% in largest diameter)
      was treated conservatively and subsequently showed stable disease on MR imaging.
      Progression-free survival was 98.7%. Another patient had symptomatic oedema
      requiring ventriculoperitoneal shunt insertion. 11 patients had serviceable
      hearing before radiotherapy and 72.7% of them retained useful hearing (20.1 dB
      mean decline in pure tone average). Facial and trigeminal nerve functions and
      sense of equilibrium were preserved in > 90% of patients. CONCLUSION:
      Radiosurgery is effective and safe for small VSs or as an adjunct therapy after
      microsurgery.

PMID- 30182130
TI  - Ingrowing toenails in children and adolescents: is nail avulsion superior to
      nonoperative treatment?
AB  - INTRODUCTION: Ingrowing toenail (IGTN) or onychocryptosis is not uncommon in
      children and adolescents. However, there is a dearth of evidence in the
      literature on the management of IGTN in this age group. This study aimed to
      compare the results of nonoperative treatment for IGTN with that of operative
      treatment among children and adolescents. METHODS: All children and adolescents
      who were treated for IGTN at our institution between 2010 and 2014 were included
      for this retrospective study. Demographic data, treatment prescribed and outcome
      at six months after presentation were analysed. RESULTS: Overall, 199 patients
      were recruited. There were 123 (61.8%) boys and 76 (38.2%) girls. Median age was
      14 years. Among 199 toes, 162 (81.4%) were treated nonoperatively, with nail care
      advice, topical antibiotics and daily cleansing. Only 37 (18.6%) toes were
      treated operatively. In the operative group, 23 (62.2%) patients underwent wedge
      resections, while the remaining 14 (37.8%) had total nail avulsions; for all
      patients, germinal matrices were preserved. At the six-month follow-up, there
      were 5 (3.1%) cases of recurrence in the nonoperative group when compared to 3
      (8.1%) recurrences in the operative group. CONCLUSION: We recommend that IGTN in
      children and adolescents be treated in the first instance by nonoperative
      methods. Operative options can be considered for resistant cases or in case of
      recurrence of IGTN.

PMID- 30182131
TI  - Accuracy of ultrasonography-guided fine needle aspiration cytology and
      significance of non-diagnostic cytology in the preoperative detection of thyroid
      malignancy.
AB  - INTRODUCTION: Thyroid fine-needle aspiration cytology (FNAC) is an established
      investigation for the preoperative evaluation of thyroid nodules and is often
      done under ultrasonography guidance. While its accuracy has been widely reported,
      there is little evidence in the literature on the approach to non-diagnostic
      cytology results. In our study, we aimed to determine the diagnostic performance
      of ultrasonography-guided thyroid FNAC for the preoperative diagnosis of thyroid
      cancer at our institution and evaluate the significance of a non-diagnostic
      thyroid FNAC. METHODS: We retrospectively reviewed the thyroid ultrasonography
      studies and medical records of all patients who underwent both thyroid FNAC and
      subsequent thyroid surgery at our institution from 2011 to 2013. FNAC results
      were correlated with final histological diagnosis from surgery and the
      ultrasonography studies were reviewed for suspicious sonographic features.
      RESULTS: FNAC predicted malignancy with sensitivity, specificity, positive
      predictive value, negative predictive value, false positive rate, false negative
      rate and total accuracy of 90.7%, 54.6%, 42.9%, 95.2%, 46.4%, 6.4% and 64.1%,
      respectively. We found that only one of 26 nodules with non-diagnostic FNAC
      results was proven malignant on a second FNAC and subsequent thyroidectomy.
      CONCLUSION: The accuracy of ultrasonography-guided FNAC at our institution was
      comparable to that reported in the literature. There appears to be very low
      probability of malignancy in sonographically benign nodules with initial non
      diagnostic FNAC results.

PMID- 30182132
TI  - Understanding the hepatitis B core positive liver donor.
AB  - The increasing number of patients on the Singapore national liver transplant
      waiting list and the lack of donor livers have necessitated a review on the
      limited use of marginal donor liver grafts. Some grafts are of good quality but
      are considered marginal due to positive donor antibody to hepatitis B virus core
      protein serology, and negative hepatitis B surface antigen (HBsAg) and hepatitis
      B DNA. The fear is of viral reactivation during periods of intense
      immunosuppression. This is made possible by the ability of the hepatitis B virion
      to reside in a dormant state within the hepatocyte nucleus despite HBsAg
      clearance, i.e. the occult hepatitis B infection (OBI). In truth, appropriate
      selection of recipients and effective post-transplantation immunoprophylaxis
      significantly reduce the risk of hepatitis B viral reactivation. This article
      explains the confusion surrounding OBI and reviews current recommendations on how
      to manage such donor liver grafts.

PMID- 30182133
TI  - Acquired Partial Lipodystrophy Associated with Anti-Mi-2 Antibody-positive Adult
      onset Dermatomyositis.

PMID- 30182134
TI  - Langerhans Cell Histiocytosis with Lymph Node Involvment Presenting as
      Erythroderma.

PMID- 30182135
TI  - Two Novel Mutations in the ERCC8 Gene in a Patient with Ultraviolet-sensitive
      Syndrome.

PMID- 30182136
TI  - Expression of n-MYC, NAMPT and SIRT1 in Basal Cell Carcinomas and their Cells of
      Origin.
AB  - Deregulated Hedgehog signalling is a driver of basal cell carcinomas. One
      effector of the Hedgehog pathway is n-MYC. c/n-MYC proteins, NAMPT and DBC1 are
      linked to SIRT1 in a positive feedback loop that may contribute to tumorigenesis
      of basal cell carcinoma. In 5 basal cell carcinoma types immunohistochemistry
      revealed n-MYC, NAMPT and SIRT1 expression. DBC1 was homogenously expressed in
      all epithelial cells. NAMPT, SIRT1 and c-MYC were expressed in the stratum basale
      of human and murine skin. In hair follicles NAMPT and SIRT1 were expressed
      together with c-MYC and n-MYC, except for the matrix, where n-MYC was strongly
      positive, but c-MYC expression was absent. Therefore, a common pathway connecting
      n-MYC, NAMPT and SIRT1 may be active in basal cell carcinomas and in their cells
      of origin. This pathway may contribute to the development of basal cell
      carcinomas. Targeting factors in the feedback loop may offer novel therapeutic
      options.

PMID- 30182137
TI  - [Analysis of comprehensive community-based health promotion approaches for
      children : Health prospects in disadvantaged neighborhoods in Germany's Ruhr
      area].
AB  - BACKGROUND: The "Growing up Healthy" research consortium investigated
      comprehensive community-based approaches to health promotion aimed at children in
      the cities of Moers and Oberhausen in Germany's Ruhr area. OBJECTIVES: The aim of
      this paper is to analyze municipal policies as well as institutional and
      sociospatial conditions for comprehensive community-based approaches under the
      following research questions: What is the implementation level of comprehensive
      community-based health promotion from the perspective of a) key community actors;
      b) administrators from day care centers, family centers, and primary schools? How
      do they assess the health prospects of disadvantaged families and families with
      migration background? METHODS: In the course of a local stocktaking, expert
      interviews were conducted with key community actors and administrators from day
      care centers, family centers, and primary schools (n = 34). RESULTS: Needs for
      development exist, particularly in the intersectoral coordination of prevention
      policies as well as in adequate mandating by municipal policymakers. The major
      hurdles faced by preschools and schools are an ailing or absent infrastructure
      and insufficient resources. The challenges faced by professionals in
      disadvantaged neighborhoods are immense: poverty, integration, and inclusion.
      CONCLUSIONS: Comprehensive community-based health promotion is still in its
      infancy. An explicit legal mandate including the commitment to provide funding
      does not exist. There are clear indications that children's health prospects vary
      widely according to urban neighborhood and educational institutions. It is
      becoming evident that preschools and schools require need-based funding.

PMID- 30182138
TI  - [The health sector and early childhood intervention: intersectoral collaboration
      in research].
AB  - BACKGROUND: Early childhood interventions are locally and regionally organized
      support services for families from pregnancy until the end of the third year of
      life. The interventions promote diverse measures to enhance parental skills in
      order to improve developmental and living circumstances. One crucial element of
      early childhood intervention in Germany are prevention networks at municipal
      level. The collaboration of healthcare professionals and child and youth welfare
      professionals in these networks aims to provide nonstigmatizing access to early
      childhood intervention for families with psychosocial burdens. From the point of
      view of the healthcare sector, the research program Together for Families (ZuFa
      Monitoring) of the National Centre on Early Prevention (NZFH) at the Federal
      Centre for Health Education (BZgA) has collected representative data at the
      interfaces of gynecology, obstetrics, pediatrics, and early childhood
      intervention since 2017. GOAL: The background and goals, as well as design and
      methods of the ZuFa Monitoring studies are described. For obstetrics clinics and
      resident pediatricians, sample descriptions, including data on representativeness
      and early data regarding collaboration quality, are given. EARLY RESULTS: The
      samples are representative for the population of obstetric clinics and resident
      pediatricians in Germany. At least two-thirds of the respondents indicate that
      the proportion of families with psychosocial burdens has increased. Care for
      psychosocially burdened families is regarded as challenging due to a lack of
      time, limited financial compensation, and aggravating conditions, such as
      language barriers. Respondents expect early childhood intervention to alleviate
      their daily work. DISCUSSION: ZuFa Monitoring collects data regarding the care
      for families with psychosocial burdens at the interface of the health and the
      child and youth welfare sector. The research program generates information on
      inhibitory as well as promoting factors, thereby informing the further
      development and expansion of prevention networks at the municipal level, and
      heightening the quality of care for families in the health sector.

PMID- 30182139
TI  - [Local public health reporting as a basis for planning health promotion for
      children].
AB  - The Health Report (Gesundheitsberichterstattung, GBE) describes the health of the
      overall population and also highlights areas or topics where specific action may
      be required. Additionally, in line with a new definition, the GBE provides an
      objective basis for participative processes, thereby building a bridge to health
      promotion concepts.Municipal integrated health strategies (municipal prevention
      chains) are based on the salutogenesis concept. One particularly important
      characteristic of prevention chains is, among others, their participative
      approach to develop need-based measures on a municipal level. This implies an
      overarching way of working and a coordinated approach between several
      stakeholders. Moreover, it requires a combination of health, social, and
      environmental data, as well as integrated GBE, which serves as a planning
      basis.In the federal state of Brandenburg, two test regions were chosen, and a
      municipal prevention chain was followed and monitored by the Health Equity
      Coordination Office (Koordinierungsstelle Gesundheitliche Chancengleichheit)
      during the implementation period. In the context of an evaluation, barriers and
      success factors were identified. During the implementation period four additional
      phases were identified and specific aspects were also assigned to these phases.
      Moreover, social environmental oriented data should be reliable, continuously
      collected, and allow for a local comparability. Data combined from different
      providers, supplemented with subjective data, could fill the gap and support
      participative processes.How a good integration in municipal planning processes
      can be successful, as well as correlated questions about necessary resources,
      will need to be investigated in future processes.

PMID- 30182140
TI  - [Nutrition as a resource for networked community based health promotion for
      children-perspectives of parents and experts].
AB  - BACKGROUND: The promotion of healthy nutrition and alimentary participation (the
      possibility of experiencing the social function of food) is an essential aspect
      of integrated overall approaches of community-based health promotion. Preschool
      and primary school settings are given particular importance in terms of the
      target group focused on by community-based approaches: children from socially
      disadvantaged families. OBJECTIVES: How do parents and practice experts describe
      the status quo, potential, and obstacles in the implementation of healthy
      nutrition practices in the settings kindergarten and elementary school? What ist
      the importance of nutrition and alimentary participation within the framework of
      the integrated overall approach attributed by practice experts? METHOD: In two
      urban centers, expert interviews were conducted with stakeholders of integrated
      overall approaches and administrators from preschools and primary schools. The
      perspectives held by parents in financially precarious situations or with
      immigrant backgrounds were explored in group discussions. RESULTS: Nutrition
      takes on an important role in the narratives of parents and experts. Preschools
      and primary schools draw upon daily interaction with food and shared meals in a
      variety of ways to foster the development of healthy eating habits and alimentary
      participation. It has become clear that preschools and primary schools must
      increasingly counteract delegation of parenting responsibilities and poor
      nutrition practices, for instance by providing socially compensatory breakfasts.
      Parents acknowledge these efforts but express criticism that food in schools is
      eaten under problematic spatial conditions and intense time pressure. DISCUSSION:
      Nutrition is used by experts as a resource but, in contrast to physical exercise
      or mental health, without reference to integrated community-based health
      promotion. Promotion of alimentary participation and healthy nutrition practice
      could have more impact if stakeholders saw themselves as essential components of
      integrated community-based health promotion.

PMID- 30182141
TI  - Significant increase of pathogen detection rate by dry arthroscopic biopsies at
      suspected low-grade infection following total knee arthroplasty: a prospective
      observational study.
AB  - INTRODUCTION: The differentiation between stiff-knee and low-grade periprosthetic
      joint infection (PJI) is the current diagnostic challenge in total knee (TKA)
      revision arthroplasty. The aim of this study was to investigate the additional
      value of dry biopsies, compared to wet biopsies, in patients presenting with knee
      stiffness following primary TKA. MATERIALS AND METHODS: Single center,
      prospective observational study. Consecutive patients with joint stiffness of
      unknown origin following primary TKA were enrolled. Patient assessment followed
      the diagnostic standard algorithm. During diagnostic arthroscopy, synovial fluid
      (synovial WBC, PMN%) and five dry biopsies (dry) were collected. Then fluid was
      infused and another five microbiology (wet) and five histological biopsies
      gathered, all from identical locations. The primary outcome parameter was the
      difference between the pathogens in wet and dry biopsies. RESULTS: 71 patients
      (61% females, 67 +/- 10 years) were eligible. Preoperative blood serology mean
      CRP (0.7 +/- 1.5 mg/dl; p = 0.852), WBC (6.6 +/- 1.7 G/l; p = 0.056), and
      synovial fluid mean WBC (1639 +/- 2111; p = 0.602), PMN% (38 +/- 28; p = 0.738)
      did not differ between patients with negative, positive wet or dry biopsies. The
      histology was in 11% positive (p = 0.058). In 32% at least one pathogen was
      detected, 48% from wet, 44% from dry biopsies. An inhomogeneous distribution was
      found. Cutibacterium acnes (100%) was solely found in wet, Micrococcus luteus
      (75%), Staphylococcus capitis (67%), and Micrococcus lylae (100%) were
      predominantly found in dry biopsies. Additional dry biopsies increased the
      pathogen detection rate by 49%. CONCLUSION: The addition of dry biopsies to the
      current standard diagnostic algorithm for PJI increased the pathogen detection
      rate by 49%.

PMID- 30182142
TI  - Quantitative correlation of mechanoreceptors in tibial remnant of ruptured human
      anterior cruciate ligament with duration of injury and its significance: an
      immunohistochemistry-based observational study.
AB  - BACKGROUND: Proprioception is a specialized sensory modality encompassing the
      movement of the joint and its position in space. Reconstruction of the anterior
      cruciate ligament (ACL) does not always yield expected outcome, suggesting that
      successful reconstruction depends on not only the ultimate strength of the graft
      but also recovery of proprioception. Treatment delay is a significant concern in
      developing countries, e.g., in Asia. Thus, presence of mechanoreceptors is one of
      the factors having paramount importance for successful outcome. We conducted this
      study to identify mechanoreceptors via immunohistochemical staining and correlate
      their presence with duration of injury. MATERIALS AND METHODS: A total of 38
      injured native ACL stumps were harvested from patients undergoing ACL
      reconstruction and stained with neurofilament protein stain to detect functional
      mechanoreceptors. RESULTS: Of the specimens, 44.7% stained positive for
      monoclonal antibody. No association was found between duration of injury and
      presence of mechanoreceptors (p = 0.897). No correlation was seen between age and
      side. CONCLUSIONS: No correlation was found between duration of injury and
      presence of viable mechanoreceptors, hence it is beneficial to preserve the
      native ACL stump irrespective of the time interval between injury and surgery.
      LEVEL OF EVIDENCE: III.

PMID- 30182143
TI  - Quantum chemical studies on anion specificity of CalphaNN motif in functional
      proteins.
AB  - Anion binding CalphaNN motif is found in functionally important regions of
      protein structures. This motif based only on backbone atoms from three adjacent
      residues, recognizes free sulphate or phosphate ion as well as phosphate groups
      in nucleotides and in a variety of cofactors. The mode of anion recognition and
      microscopic picture of binding interaction remains unclear. Here we perform self
      consistent quantum chemical calculations considering sulphate and phosphate bound
      CalphaNN motif fragments from crystal structures of functional proteins in order
      to figure out microscopic basis of anion recognition. Our calculations indicate
      that stability and preference of the anion in the motif depends on the sequence
      of the motif. The stabilization energy is larger in case of polar residue
      containing motif fragment. Nitrogen atom of the polar residue of motif mainly
      participates in the coordination at the lowest energy levels. Anion replacement
      decreases stabilization energy along with coordination between motif atoms and
      oxygen atoms of anion shifted to higher energies, suggesting preference of the
      motif residues to specific anion. Our analysis may be helpful to understand
      microscopic basis of interaction between proteins and ionic species.

PMID- 30182144
TI  - Discovery of novel wee1 inhibitors via structure-based virtual screening and
      biological evaluation.
AB  - Wee1 plays a critical role in the arrest of G2/M cell cycle for DNA repair before
      entering mitosis. Many cancer cells have been identified as overexpression of
      Wee1. In this research, pharmacophore modeling, molecular docking and molecular
      dynamics simulation approaches were constructed to identify novel potential Wee1
      inhibitors. A compound 8 was found to have a novel skeleton against Wee1 with an
      IC50 value of 22.32 uM and a Ki value of 13.11 uM. Kinetic assays were employed
      to evaluate the compound 8 as a competitive inhibitor. Compound 8 was tested
      against A-549 tumor cell lines with IC50 value of 17.8 uM. To investigate the
      intermolecular interaction of Wee1 and compound 8, further molecular dynamics
      simulations were performed. It indicates that the binding mode of compound 8 and
      reference ligand is similar. The active core scaffold of compound 8 could
      represent a promising lead compound for studying Wee1 and be used for further
      structural optimization to design more potent Wee1 inhibitors.

PMID- 30182145
TI  - Influence of magnesium chloride on the dose-response of polyacrylamide-type gel
      dosimeters.
AB  - We investigated the effect of magnesium chloride (MgCl2) on the nuclear magnetic
      resonance dose-response of polyacrylamide-type (PAGAT, NIPAM, and VIPET) gel
      dosimeters containing acrylamide, N-isopropylacrylamide, and N-vinylpyrrolidone
      as a monomer, respectively. The dose-transverse relaxation rates (1/T2 = R2)
      obtained from magnetic resonance imaging data revealed that a substantial
      increase in the dose-R2 response occurred as the concentration of MgCl2 in the
      gel dosimeters increased. The sensitivity of the PAGAT gel with 1.0 M MgCl2 was
      found to be approximately one order higher than that of the same gel without
      MgCl2. In addition, the water equivalences of the gels with MgCl2 were evaluated
      over a wide range of photon energies. The results indicated that MgCl2 acts as a
      powerful sensitizer to radiation-induced free-radical polymerization in
      polyacrylamide-type gel dosimeters, but does not interfere with the desirable
      properties of basic polyacrylamide-type gel dosimeters (i.e., the dose rate and
      dose integration).

PMID- 30182146
TI  - Autophagy modulation: a prudent approach in cancer treatment?
AB  - Autophagy is a tightly controlled process comprising lysosomal degradation and
      recycling of cellular proteins and organelles. In cancer, its paradoxical dual
      role of cytoprotection and cytotoxicity is context-dependent and controversial.
      Autophagy primarily acts as a mechanism of tumour suppression, by maintenance of
      genomic integrity and prevention of proliferation and inflammation. This,
      combined with immune-surveillance capabilities and autophagy's implicated role in
      cell death, acts to prevent tumour initiation. However, established tumours
      exploit autophagy to survive cellular stresses in the hostile tumour
      microenvironment. This can lead to therapy resistance, one of the biggest
      challenges facing current anti-cancer approaches. Autophagy modulation is an
      exciting area of clinical development, attempting to harness this fundamental
      process as an anti-cancer strategy. Autophagy induction could potentially prevent
      tumour formation and enhance anti-cancer immune responses. In addition, drug
      induced autophagy could be used to kill cancer cells, particularly those in which
      the apoptotic machinery is defective. Conversely, autophagy inhibition may help
      to sensitise resistant cancer cells to conventional chemotherapies and
      specifically target autophagy-addicted tumours. Currently, hydroxychloroquine is
      in phase I and II clinical trials in combination with several standard
      chemotherapies, whereas direct, deliberate autophagy induction remains to be
      tested clinically. More comprehensive understanding of the roles of autophagy
      throughout different stages of carcinogenesis has potential to guide development
      of novel therapeutic strategies to eradicate cancer cells.

PMID- 30182147
TI  - A phase I clinical trial of hepatic arterial infusion of oxaliplatin and oral
      capecitabine, with or without intravenous bevacizumab, in patients with advanced
      cancer and predominant liver involvement.
AB  - BACKGROUND: We investigated hepatic arterial infusion (HAI) oxaliplatin combined
      with capecitabine +/- bevacizumab in advanced cancer with predominant liver
      involvement. METHODS: Patients received HAI oxaliplatin (140 mg/m2) and
      escalating doses of capecitabine (500, 750, and 1000 mg/m2), with (Group 1) or
      without (Group 2) bevacizumab (10 mg/kg IV). A 3 + 3 dose design was used,
      followed by an expansion phase. RESULTS: From 9/2009 to 2/2014, 61 patients (34
      men, 27 women) were enrolled (Group 1 = 44; Group 2 = 17). Patients were treated
      in Group 2 if they had contraindications to bevacizumab (n = 13) or if there was
      no opening in Group 1 (n = 4). The median age was 60 years (range, 20-88). The
      most common cancers were colorectal (22 patients), liver (12), pancreatic (7),
      breast (4), and biliary tract (4). The median number of prior therapies was 3
      (range, 1-12); 32 (53%) patients had received oxaliplatin. The dose-limiting
      toxicity was Grade 3 diarrhea and occurred in 2 patients receiving 1000 mg/m2
      capecitabine. The maximum tolerated dose was HAI oxaliplatin 140 mg/m2,
      capecitabine 750 mg/m2, and bevacizumab 10 mg/kg. The most common toxicities were
      nausea/vomiting, anemia, thrombocytopenia, neutropenia, and hypomagnesemia. The
      rates of partial response and stable disease >= 4 months were 22% and 39% (Group
      1) and 9% and 0% (Group 2). The respective median time to treatment failure and
      overall survival were 3 and 6.9 months (Group 1) and 1.5 and 5.9 months (Group
      2). CONCLUSION: HAI oxaliplatin combined with capecitabine +/- bevacizumab was
      well-tolerated and was associated with favorable outcomes in selected patients.

PMID- 30182148
TI  - A metabolic and genomic assessment of sugar fermentation profiles of the
      thermophilic Thermotogales, Fervidobacterium pennivorans.
AB  - A metabolic, genomic and proteomic assessment of Fervidobacterium pennivorans
      strains was undertaken to clarify the metabolic and genetic capabilities of this
      Thermotogales species. The type strain Ven5 originally isolated from a hot mud
      spa in Italy, and a newly isolated strain (DYC) from a hot spring at Ngatamariki,
      New Zealand, were compared for metabolic and genomic differences. The
      fermentation profiles of both strains on cellobiose generated similar major end
      products (acetate, alanine, glutamate, H2, and CO2). The vast majority of end
      products produced were redox neutral, and carbon balances were in the range of 95
      115%. Each strain showed distinct fermentation profiles on sugar substrates. The
      genome of strain DYC was sequenced and shown to have high sequence similarity and
      synteny with F. pennivorans Ven5 genome, suggesting they are the same species.
      The unique genome regions in Ven5, corresponded to genes involved in the Entner
      Doudoroff pathway confirming our observation of DYC's inability to utilize
      gluconate. Genome analysis was able to elucidate pathways involved in production
      of the observed end-products with the exception of alanine and glutamate
      synthesis which were resolved with less clarity due to poor sequence identity and
      missing critical enzymes within the pathway, respectively.

PMID- 30182149
TI  - A Critical Review of the "Undoing Hypothesis": Do Positive Emotions Undo the
      Effects of Stress?
AB  - Research in affective science has shown that trait positive affect reduces the
      risk of developing disease and is protective against the progression of certain
      diseases. Research also suggests that trait positive affect predisposes
      individuals to more frequent experiences of positive emotional states. The
      undoing effect has been proposed as a potential mechanism explaining how positive
      emotions influence health outcomes. According to this hypothesis, the experience
      of state positive emotions or positive affect contributes to faster recovery from
      the body's physiological response to stress. This paper critically reviews
      literature concerning the undoing hypothesis. Several common methodological
      weaknesses were identified, including conceptual and design issues. Based on the
      reviewed studies two separate conclusions were drawn. First, there was
      insufficient evidence to conclude that the occurrence of positive emotional
      states speeds physiological recovery. Second, there was insufficient evidence to
      evaluate the undoing hypothesis as a potential mechanism through which state
      positive emotions affect health. Future research should focus on identifying the
      key parameters responsible for demonstrating the undoing effect when it is
      observed in order to understand how the experience of positive emotions may exert
      positive effects on health outcomes.

PMID- 30182150
TI  - Barriers to physical activity: a study of academic and community cancer survivors
      with pain.
AB  - PURPOSE: Despite the numerous benefits of physical activity (PA) for patients
      with cancer, many cancer survivors report challenges to participating in PA. The
      objectives of this study were (1) to assess barriers to PA and (2) to examine
      participant characteristics associated with modifiable barriers to PA among
      cancer survivors with pain. METHODS: We conducted a cross-sectional survey study
      at one academic medical center and 11 community hospitals. Participants completed
      the 12-item Physical Activity Barriers After Cancer (PABAC) instrument
      (Cronbach's alpha = 0.75). Multivariable regression models examined participant
      characteristics associated with PABAC scores with a higher score indicating more
      barriers to PA. RESULTS: Among 662 survivors, 67% had moderate or severe pain
      (rating 4 or greater on a scale of 0 to 10). Seventy-five percent of survivors
      did not meet the American Cancer Society PA recommendations on average, and these
      individuals had higher mean PABAC scores (beta coefficient (beta) = 2.02, 95%
      confidence interval (CI) 0.96-3.09, p < 0.001). In adjusted analyses, cancer
      survivors who were non-white (beta = 1.55, 0.28-2.82, p = 0.02), treated at a
      community hospital (beta = 1.07, 0.09-2.05, p = 0.03), had surgery (beta = 1.69,
      0.69-2.69, p = 0.001), or within 12 months of diagnosis (beta = 1.15, 0.20-2.10,
      p = 0.02) reported greater barriers to PA. CONCLUSIONS: The majority of cancer
      survivors with pain are not adequately participating in PA. Key demographic and
      clinical characteristics are associated with survivors' barriers. IMPLICATIONS
      FOR CANCER SURVIVORS: Efforts to overcome specific barriers are needed to promote
      PA after a cancer diagnosis.

PMID- 30182151
TI  - Assessing the Bacterial Community Structure in the Rhizoplane of Wetland Plants.
AB  - Plant-microorganism interaction in the rhizosphere is important for nutrient
      cycling, carbon sequestration in natural ecosystems, contaminant elimination and
      ecosystem functioning. Abundance of microbial communities and variation in
      species composition can be an imperative determinant of phytoremediation
      capability. In the present study we have assessed the bacterial community
      structure in the rhizoplane of wetland plants, Acorus calamus, Typha latifolia,
      and Phragmites karka using Terminal restriction fragment length polymorphism
      technique. The most dominant phylum, in the plants under study, was phylum
      Firmicutes, followed by Proteobacteria and Actinobacteria. Bacterial groups
      belonging to phylum Chloroflexi, Acidobacteria, Deferribacteres and Thermotogae
      also showed their presence in P. karka and T. latifolia but were absent in A.
      calamus. Diversity indices of bacterial community were assessed. The results of
      this study show the presence of bacterial phyla which play an important role in
      bioremediation of contaminants. Thus these plants can be used as potential
      candidates of phytoremediation.

PMID- 30182152
TI  - Contribution of hip abductor-adductor muscles on static and dynamic balance of
      community-dwelling older adults.
AB  - BACKGROUND: The previous studies have investigated causes of and risk factors for
      falls and impairment of functional capability in older adults. However, the
      biomechanical factors involved in functional performance and postural control,
      and the contribution of hip muscles, are still unknown. AIMS: The aim of the
      present study was to verify the association between the muscle function of hip
      abductors and adductors and static and dynamic balance, in a narrow base of
      support, in community-dwelling older adults. METHODS: Eighty-one older adults,
      including both women and men, were evaluated. Tandem gait and single-leg stance
      were used to assess static and dynamic balance, and an isokinetic dynamometer was
      used to analyze muscle function (peak torque and rate of torque development
      according to body weight). Data were analyzed by a multivariate linear regression
      test without adjustment and with adjustment using two models: adjustment I (sex)
      and adjustment II (age). RESULTS: There was a statistically significant
      association between peak torque of abductor in single-leg stance and tandem gait
      speed. The PT of hip adductors contributed to static balance performance, in a
      narrow base of support from the unadjusted data and from the adjusted data by
      sex. CONCLUSION: The findings of the present study are relevant, because if
      deficits in balance and functionality in older adults can be linked to a decline
      in maximum muscle strength of hip abductors, this parameter can be treated to
      maintain independence in older adults for as long as possible.

PMID- 30182153
TI  - Initial Riociguat Monotherapy and Transition from Sildenafil to Riociguat in
      Patients with Idiopathic Pulmonary Arterial Hypertension: Influence on Right
      Heart Remodeling and Right Ventricular-Pulmonary Arterial Coupling.
AB  - PURPOSE: To evaluate the influence of riociguat on World Health Organization
      functional class (WHO FC), 6-min walk distance (6MWD), right heart remodeling,
      and right ventricular-pulmonary arterial (RV-PA) coupling in patients with
      idiopathic pulmonary arterial hypertension (IPAH) who are treatment-naive or who
      have failed to achieve treatment goals with sildenafil therapy. METHODS: Twenty
      patients with IPAH were enrolled: 12 had not previously received PAH-targeted
      therapy (treatment-naive subgroup) and 8 had been receiving sildenafil therapy
      but failed to achieve treatment goals; on entering this pilot study these 8
      patients were switched from sildenafil to riociguat therapy (treatment-switch
      subgroup). Patients received riociguat individually dose-adjusted up to a maximum
      of 2.5 mg three times daily. After 12 weeks, patients were assessed for WHO FC,
      6MWD, right heart remodeling, and RV-PA coupling. RESULTS: Riociguat
      significantly improved WHO FC in treatment-naive patients (from 0/4/8/0 patients
      in WHO I/II/III/IV at baseline to 1/6/5/0 at week 12) and in treatment-switch
      patients (from 0/4/4/0 patients in WHO I/II/III/IV at baseline to 1/4/3/0 at week
      12). Additionally, treatment-naive and treatment-switch patients showed
      significant improvements at week 12 versus baseline in 6MWD (increases of + 76.8
      m and + 71.6 m, respectively), RV systolic function, and RV-PA coupling.
      CONCLUSION: These results support the proven efficacy of riociguat in patients
      with IPAH, including treatment-naive patients and those switching to riociguat
      following failure to achieve treatment goals with sildenafil, and suggest that it
      may be possible to delay disease progression in this patient group.

PMID- 30182154
TI  - Annexin A5 Protein as a Potential Biomarker for the Diagnosis of Asthma.
AB  - PURPOSE: Annexin A5 (ANXA5) has a potential role in cellular signal transduction,
      inflammation, and fibrosis. However, the exact role of ANXA5 in asthma remains to
      be clarified. The aims of the present study were to investigate ANXA5 protein
      expression in a mouse model of asthma and pollutant exposure and to elucidate the
      relationships between clinical variables and plasma ANXA5 levels in patients with
      asthma. METHODS: A murine model of asthma induced by ovalbumin (OVA) and titanium
      dioxide (TiO2) nanoparticles has been established using BALB/c mice, and we
      examined ANXA5 expression and lung fibrosis using this model. Moreover, we also
      compared ANXA5 plasma levels in patients with controlled vs. exacerbated asthma.
      RESULTS: ANXA5 protein levels were lower in lung tissue from OVA + OVA mice than
      in control mice. Lung ANXA5, connective tissue growth factor (CTGF), and
      transforming growth factor beta1 (TGF-beta1) protein levels were higher in OVA +
      TiO2-exposed mice than in control or OVA + OVA mice. Although Dermatophagoides
      pteronyssinus (Derp1) treatment increased lung ANXA5 protein levels in MRC-5
      cells and A549 epithelial cells, it decreased lung ANXA5 levels in NHBE cells.
      Treatment with TiO2 nanoparticles increased lung ANXA5, CTGF, and TGF-beta1
      protein levels in MRC-5 cells, A549 epithelial cells, and NHBE cells. Plasma
      ANXA5 levels were lower in asthmatic patients than in healthy controls, and they
      were significantly enriched in patients with exacerbated asthma compared with
      those with controlled asthma (P < 0.05). ANXA5 levels were correlated with
      pulmonary function as assessed by spirometry. CONCLUSION: Our results imply that
      ANXA5 plays a potential role in asthma pathogenesis and may be a promising marker
      for exacerbated bronchial asthma and exposure to air pollutants.

PMID- 30182155
TI  - Contribution of forest wood products to negative emissions: historical
      comparative analysis from 1960 to 2015 in Norway, Sweden and Finland.
AB  - BACKGROUND: Forests and forest products can significantly contribute to climate
      change mitigation by stabilizing and even potentially decreasing the
      concentration of carbon dioxide (CO2) in the atmosphere. Harvested wood products
      (HWP) represent a common widespread and cost-efficient opportunity for negative
      emissions. After harvest, a significant fraction of the wood remains stored in
      HWPs for a period that can vary from some months to many decades, whereas
      atmospheric carbon (C) is immediately sequestered by vegetation re-growth. This
      temporal mismatch between oxidation of HWPs and C uptake by vegetation generates
      a net sink that lasts over time. The role of temporary carbon storage in forest
      products has been analysed and debated in the scientific literature, but detailed
      bottom-up studies mapping the fate of harvested materials and quantifying the
      associated emission profiles at national scales are rare. In this work, we
      quantify the net CO2 emissions and the temporary carbon storage in forest
      products in Norway, Sweden and Finland for the period 1960-2015, and investigate
      their correlation. We use a Chi square probability distribution to model the
      oxidation rate of C over time in HWPs, taking into consideration specific half
      lives of each category of products. We model the forest regrowth and estimate the
      time-distributed C removal. We also integrate the specific HWP flows with an
      emission inventory database to quantify the associated life-cycle emissions of
      fossil CO2, CH4 and N2O. RESULTS: We find that assuming an instantaneous
      oxidation of HWPs would overestimate emissions of about 1.18 billion t CO2
      (cumulative values for the three countries over the period 1960-2015).We also
      find that about 40 years after 1960, the starting year of our analysis, are
      sufficient to detect signs of negative emissions. The total amount of net CO2
      emissions achieved in 2015 are about - 3.8 million t CO2, - 27.9 t CO2 and - 43.6
      t CO2 in Norway, Sweden, and Finland, respectively. CONCLUSION: We argue for a
      more explicit accounting of the actual emission rates from HWPs in carbon balance
      studies and climate impact analysis of forestry systems and products, and a more
      transparent inclusion of the potential of HWP as negative emissions in
      perspective studies and scenarios. Simply assuming that all harvested carbon is
      instantaneously oxidized can lead to large biases and ultimately overlook the
      benefits of negative emissions of HWPs.

PMID- 30182156
TI  - Mild cognitive impairment and progression to dementia in people with diabetes,
      prediabetes and metabolic syndrome: a systematic review and meta-analysis.
AB  - PURPOSE: We aimed to quantify the relative risk of progression from mild
      cognitive impairment (MCI) to dementia in people with and without diabetes, and
      with and without the MetS (MetS); and to identify potential modifiers of the risk
      of progression from MCI to dementia in people with diabetes or MetS. METHODS: We
      searched Medline, Embase, PsycINFO, PsycArticles and Web of Science from
      inception through to 20th March 2018. Where possible, the results from three or
      more studies were pooled in a meta-analysis, while other findings have been
      described narratively. RESULTS: We included 15 articles reporting 12 studies
      (6865 participants). The overall unadjusted pooled odds ratio for the progression
      of MCI to dementia in people with diabetes/MetS was 1.67 (95% CI 1.27-2.19); the
      pooled odds ratio for progression in diabetes + MCI was 1.53 (95% CI 1.20-1.97)
      and in people with MetS + MCI was 2.95 (95% CI 1.23-7.05). There was moderate
      heterogeneity in the included studies (I2 < 60%). In diabetes, a longer duration
      of diabetes and the presence of retinopathy were associated with an increased
      risk of progression, while the use of statins and oral hypoglycaemic agents
      reduced the risk. Having multiple cardiovascular risk factors was a significant
      risk factor for progression from MCI to dementia in people with MetS.
      CONCLUSIONS: Diabetes and MetS were both associated with an increased incidence
      of dementia when co-existing with MCI. Intensive cardiovascular risk reduction
      and lifestyle changes for patients presenting with MCI and diabetes, prediabetes
      or MetS may be important in reducing incidence of dementia in this high risk
      population.

PMID- 30182157
TI  - Endothelial damage and thromboembolic risk after pulmonary vein isolation using
      the latest ablation technologies: a comparison of the second-generation
      cryoballoon vs. contact force-sensing radiofrequency ablation.
AB  - Experimental data suggest that cryoenergy is associated with less endothelial
      damage and thrombus formation than radiofrequency energy. This study aimed to
      compare the impact of pulmonary vein isolation (PVI) on the endothelial damage,
      myocardial damage, inflammatory response, and prothrombotic state between the two
      latest technologies, second-generation cryoballoon (CB2) and contact force
      sensing radiofrequency catheter (CFRF) ablation. Eighty-six paroxysmal atrial
      fibrillation (AF) patients (55 men; 65 +/- 12 years) underwent PVI with either
      the CB2 (n = 64) or CFRF (n = 22). Markers of the endothelial damage (L
      arginine/asymmetric dimethylarginine [ADMA]), myocardial injury (creatine kinase
      MB [CK-MB], troponin-T, and troponin-I), inflammatory response (high-sensitive C
      reactive protein), and prothrombotic state (D-dimer, soluble fibrin monomer
      complex, and thrombin-antithrombin complex) were determined before and up to 24-h
      post-procedure. The total application time was shorter (1,460 +/- 287 vs. 2,395
      +/- 571 [sec], p < 0.01) and total procedure time tended to be shorter (199 +/-
      37 vs. 218 +/- 38 [min], p = 0.06) with CB2 than CFRF ablation. The amount of
      myocardial injury was greater (CK-MB: 45 +/- 17 vs. 11 +/- 3 [IU/l], p < 0.01)
      with CB2 than CFRF ablation. The L-arginine/ADMA ratio was lower (160 +/- 51 vs.
      194 +/- 38, p = 0.028) after CB2 than CFRF ablation. Inflammatory and all
      prothrombotic markers were significantly elevated post-ablation; however, the
      magnitude was similar between the two groups. During a mean follow-up of 20 +/- 6
      months, the single-procedure AF freedom was similar between the CB2 and CFRF
      groups (60/64 vs. 20/22, p = 0.82). CB2-PVI produces significantly lesser
      endothelial damage with greater myocardial injury than CFRF-PVI; however, similar
      anticoagulant regimens are required during the peri-procedural periods in both
      technologies.

PMID- 30182158
TI  - Preparation and cytocompatibility of a novel bismuth aluminate/calcium phosphate
      cement with high radiopacity.
AB  - In a minimally invasive surgery, using a bone cement being radiologically
      detectable is vital to the success of the procedure and avoiding cement leakage
      in the early stage. The radiopacity of calcium phosphate cement (CPC) is
      inadequate, thus limiting its clinic application in this area. In this work,
      bismuth aluminate (BiA) was employed as a radiopaque agent for CPC. The
      influences of BiA on physicochemical, radiopaque and in vitro biocompatible
      properties of CPC were investigated. With the increasing content of BiA, the
      setting time and the compressive strength of CPC were augmented, while the
      injectability of the cement pastes was reduced. The radiopacity of CPC was
      significantly improved by adding more than 6 wt.% BiA. CPC specimens with less
      than 12 wt.% BiA showed good cellular affinity. Moreover, the CPC containing 6
      and 9 wt.% BiA promoted the cell growth and ALP activity of mouse bone marrow
      mesenchymal stem cells when compared with the control. On the basis of its
      improved radiopacity and cytocompatibility, the radiopaque CPC with 6 ~ 9 wt.%
      BiA is expected to be a potential substitute for bone defect restoration via
      minimally invasive surgery. CPC with bismuth aluminate reveals better radiopacity
      and cell affinity along with proper physicochemical properties.

PMID- 30182159
TI  - Bevacizumab and re-irradiation for recurrent high grade gliomas: does sequence
      matter?
AB  - PURPOSE/OBJECTIVES: We report the outcomes of the largest cohort to date of
      patients receiving both bevacizumab (BEV) and fractionated stereotactic
      radiotherapy (FSRT) for progressive or recurrent high grade glioma (HGG).
      Furthermore, the sequence of these two treatment regimens was analyzed to
      determine an optimal treatment paradigm for recurrent HGG. MATERIALS/METHODS:
      After Institutional Review Board approval, patients with pathologically confirmed
      WHO grade III anaplastic astrocytoma (AA) or IV glioblastoma multiforme (GBM)
      glioma who subsequently underwent re-irradiation at recurrence with FSRT were
      retrospectively reviewed. Patients from this group who had received BEV were also
      identified. Survival from initial diagnosis, as well as from recurrence and re
      irradiation, were analyzed as study endpoints. Date of recurrence was defined as
      the date of radiographic evidence of progressive/recurrent disease. Kaplan-Meier
      curves were generated utilizing a log-rank test with a p-value <= 0.05 considered
      significant to compare treatment sequences in terms of survival outcomes.
      RESULTS: A total of 118 patients with recurrent/progressive HGG (GBM = 87, AA =
      31) had received both BEV and FSRT. Patient characteristics were as follows:
      median KPS at recurrence was 80 (range 50-100); median age at recurrence was 57
      years; median time to radiographic recurrence/progression was 10.8 months (mo)
      and 33.1% of patients had surgery for recurrence. The median time from the start
      of BEV to FSRT was 6.4 months and from FSRT to the start of BEV was 5.1 months.
      For the entire cohort, median overall survival (OS) was 26.7 months and median
      survival time (MST) from recurrence was 13.8 months (24.4 months and 11.9 months
      for GBM only). In patients that received BEV prior to FSRT (n = 50), median OS
      and MST from recurrence were 25.2 and 13.3 months respectively. In patients
      receiving FSRT first (n = 56), median OS and MST from recurrence were 28.8 months
      and 13.9 months, respectively. Sequencing of BEV and FSRT at recurrence was not
      significantly associated with OS (p = 0.08) or median survival from recurrence (p
      = 0.75). CONCLUSIONS: The combination of FSRT and BEV for recurrent/progressive
      HGG provides promising results in terms of overall survival and survival from
      recurrence. Combining these treatment modalities appears to improve upon the
      historic outcomes of either treatment alone. The outcomes data from this study
      support the ongoing RTOG trial exploring the combination of BEV and FSRT for
      recurrent HGG.

PMID- 30182161
TI  - Introduction: the Glycobiology of nervous system.

PMID- 30182160
TI  - Prediction value of unmeasurable MR enhancement at early stage after gross-total
      resection on the survival state of patients with high-grade glioma.
AB  - PROPOSE: To explore the value of unmeasurable enhancement pattern of residual
      cavity in predicting survival at early stage after gross-total resection in high
      grade glioma (HGG) patients. METHODS: This retrospective study enrolled
      consecutive 51 HGG patients with unmeasurable enhancement who underwent gross
      total resection followed by concurrent chemoradiotherapy and adjuvant
      chemotherapy. We evaluated the enhancement patterns of residual cavity on
      contrast-T1WI made within 1 month after tumor resection (20 +/- 3 days). The
      survival state of different enhancement was compared. RESULTS: Thin-linear, thick
      linear and nodular enhancement were observed in 22 patients (43%), 10 patients
      (20%), and 19 patients (37%), respectively. The progression-free survival of
      patients with thin-linear (487, 151-887 days) was longer than those patients with
      thick-linear (277, 133-573 days), and nodular enhancement (210, 120-765 days) (P
      = 0.002). The overall survival of patients with thin-linear (774, 457-1343 days)
      was longer than those with thick-linear (462, 320-678 days), and nodular
      enhancement (326, 234-1393 days) (P = 0.002). There was no significant difference
      of orthogonal value between thick-linear and nodular enhancement (0.854), neither
      between grade III and IV with same enhancement patterns (P = 0.540, P = 0.720).
      CONCLUSIONS: The unmeasurable enhancement patterns in HGG patients within 1 month
      after gross-total resection, which might be better than the grade of tumor, holds
      a potential marker in survival state.

PMID- 30182162
TI  - A case of chronic pancreatitis exacerbation associated with pancreatic
      arteriovenous malformation: a case report and literature review.
AB  - A 60-year-old man with an unruptured cerebral aneurysm and family history of
      moyamoya disease was admitted to our hospital with epigastric pain since the
      previous day. Serum levels of pancreatic enzyme were elevated and abdominal
      contrast-enhanced computed tomography showed localized enlargement of the
      pancreatic tail in the arterial phase and revealed numerous areas of fine mesh
      like vascular hyperplasia consistent with an enlarged pancreatic tail. We
      diagnosed pancreatic arteriovenous malformation (P-AVM) with acute pancreatitis.
      Furthermore, in the pancreatic body, endoscopic ultrasonography showed lobularity
      (honeycombing type) and hyperechoic foci (non-shadowing), which suggests chronic
      pancreatitis. Acute management was performed with conservative treatment
      including administration of replacement fluids and proteolytic enzyme inhibitor.
      Distal pancreatectomy for P-AVM was performed because P-AVM is associated with
      acute pancreatitis recurrence, development of portal hypertension, progression of
      chronic pancreatitis, and refractory duodenal bleeding. Histological findings on
      the resected specimens revealed the anastomosis of abnormal arteries and veins,
      which suggested P-AVM. In addition, inflammation accompanied by fat necrosis due
      to ischemic infarction in the pancreatic tail, which suggested acute
      pancreatitis, and mild fibrosis in the pancreatic body, which suggested chronic
      pancreatitis, were shown. Although P-AVM is associated with various
      complications, symptomatic P-AVM should be considered a chronic and progressive
      disease.

PMID- 30182163
TI  - Correction to: Transcatheter valve-in-valve implantation (VinV-TAVR) for failed
      surgical aortic bioprosthetic valves.
AB  - Unfortunately, an error occurred in the original article.

PMID- 30182164
TI  - Computed tomography angiography for guiding and follow-up of magnesium
      bioresorbable scaffold implantation.

PMID- 30182165
TI  - Remaining challenges in catheter ablation of accessory pathways: rare entity of
      coronary sinus diverticulum-associated pathways.
AB  - INTRODUCTION: A limited number of case reports of coronary sinus (CS) diverticula
      complicating catheter ablation have been published. METHODS AND RESULTS: We
      retrospectively analysed 2245 patients who underwent ablation of an accessory
      pathway (AP) at our institution between 1/11/1993 and 31/10/2016. Eight patients
      (0.36%) were found to have a CS diverticulum in venography. APs showed a mean
      antegrade conduction time of 276 +/- 23 ms (range 220-310 ms) and a mean
      retrograde conduction of 301 +/- 45 ms (230-350 ms). Four patients had 1 (n = 2),
      2 (n = 1), or 3 (n = 1) previously failed ablation attempts. Pathways could not
      be ablated with a conventional 4 mm tip catheter in 7 of 8 cases. In seven
      patients, ablation was successful, in two using an 8-mm ablation catheter, in two
      using cryoablation, and in the remaining three with an irrigated tip ablation
      catheter. After failed femoral approach, one 9-year-old female was successfully
      ablated via the right jugular vein. In one 75-year-old female, ablation was not
      successful. During a mean follow-up of 8.9 +/- 6.4 years, all patients remained
      free of recurrences. CONCLUSION: In inferoseptal pathways, especially with
      previous failed ablation attempts, venographies of the CS should be performed.
      After successful ablation long-term prognosis is excellent.

PMID- 30182166
TI  - Serum ferritin level is associated with liver steatosis and fibrosis in Korean
      general population.
AB  - BACKGROUND: Elevation of serum ferritin levels is frequently observed in non
      alcoholic fatty liver disease (NAFLD) patients. Our study aims to examine the
      association between serum ferritin levels and NAFLD in Korean population. METHODS
      AND RESULTS: A total of 25,597 participants were selected from Korean National
      Health and Nutritional Examination Surveys 2007-2012. The NAFLD liver fat score
      (NLFS) was used to define NAFLD. Elevation of ALT levels was defined as ALT level
      > 40 IU/L for male and ALT level > 31 IU/L for female. Multiple logistic
      regression was used to examine the association of serum ferritin levels and NAFLD
      by sex. After adjusting for multiple covariates, the ORs (95% CI) of the elevated
      ALT levels were 1.56 (95% CI: 1.17-2.07), 1.84 (95% CI: 1.39-2.45), and 4.08 (95%
      CI: 3.08-5.40) for the second, third and fourth serum ferritin quartiles in male
      (p for trend < 0.01), 1.67 (95% CI: 1.24-2.23), 2.23 (95% CI: 1.68-2.96), and
      5.72 (95% CI: 4.32-7.60) for the second, third and fourth serum ferritin
      quartiles in female (p for trend < 0.01). Serum ferritin levels were also
      significantly associated with NAFLD and liver fibrosis both in male and female.
      CONCLUSIONS: Elevation of serum ferritin level is significantly associated with
      NAFLD and blood ALT elevation in Korean general population.

PMID- 30182167
TI  - Long-term follow-up of a community sample of adolescents with frequent headaches.
AB  - BACKGROUND: Several outcome studies have reported on the short- and long-term
      effects of migraine in selected clinical samples of children and adolescents.
      However, current knowledge of the course, incidence, and outcome predictors of
      frequent headaches in early adolescents in community populations is limited, and
      little is known about the long-term effects. Headache remains untreated in most
      of these young people. Here we examined the course, incidence, and outcome
      predictors of frequent headaches (at least once a week) over the long term (14
      years) using previously assessed data at the baseline and 1-year follow-up of
      early adolescents. METHODS: Out of an original sample of 2440 who participated in
      the first two assessments, a sample of 1266 participants (51.9% response rate)
      aged 26-28 years (mean = 27.2 years) completed an electronic questionnaire
      comprising questions about their headache frequency and duration at the long-term
      follow-up. These headache characteristics together with gender, age, parental
      divorce, number of friends, school absence, impairment of leisure-time activities
      and seeing friends, pain comorbidity, and emotional (in particular, depressive
      symptoms) and behavioral problems were analyzed. RESULTS: In these young people,
      8.4% reported frequent headaches (at least once a week) at the extended follow
      up, while 19% of the participants having such headaches at baseline again
      reported such levels with a negligible gender difference. Over the follow-up
      period, 7.4% had developed frequent headaches, and a higher percentage of females
      reported such headaches (11.3% in females, 1.5% in males). In a multivariate
      model, frequent headaches at the baseline, gender (worse prognosis in females),
      impairment of leisure-time activities and seeing friends, and higher level of
      depressive symptoms significantly predicted headache frequency at the long-term
      follow-up. CONCLUSIONS: Our findings suggest that gender, greater social
      impairment, and comorbid depressive symptoms are important indicators for both
      the short- and long-term prognosis of frequent headaches in early adolescents in
      community populations.

PMID- 30182168
TI  - A systems approach to assess climate change mitigation options in landscapes of
      the United States forest sector.
AB  - BACKGROUND: United States forests can contribute to national strategies for
      greenhouse gas reductions. The objective of this work was to evaluate forest
      sector climate change mitigation scenarios from 2018 to 2050 by applying a
      systems-based approach that accounts for net emissions across four interdependent
      components: (1) forest ecosystem, (2) land-use change, (3) harvested wood
      products, and (4) substitution benefits from using wood products and bioenergy.
      We assessed a range of land management and harvested wood product scenarios for
      two case studies in the U.S: coastal South Carolina and Northern Wisconsin. We
      integrated forest inventory and remotely-sensed disturbance data within a
      modelling framework consisting of a growth-and-yield driven ecosystem carbon
      model; a harvested wood products model that estimates emissions from commodity
      production, use and post-consumer treatment; and displacement factors to estimate
      avoided fossil fuel emissions. We estimated biophysical mitigation potential by
      comparing net emissions from land management and harvested wood products
      scenarios with a baseline ('business as usual') scenario. RESULTS: Baseline
      scenario results showed that the strength of the ecosystem carbon sink has been
      decreasing in the two sites due to age-related productivity declines and
      deforestation. Mitigation activities have the potential to lessen or delay the
      further reduction in the carbon sink. Results of the mitigation analysis
      indicated that scenarios reducing net forest area loss were most effective in
      South Carolina, while extending harvest rotations and increasing longer-lived
      wood products were most effective in Wisconsin. Scenarios aimed at increasing
      bioenergy use either increased or reduced net emissions within the 32-year
      analysis timeframe. CONCLUSIONS: It is critical to apply a systems approach to
      comprehensively assess net emissions from forest sector climate change mitigation
      scenarios. Although some scenarios produced a benefit by displacing emissions
      from fossil fuel energy or by substituting wood products for other materials,
      these benefits can be outweighed by increased carbon emissions in the forest or
      product systems. Maintaining forests as forests, extending rotations, and
      shifting commodities to longer-lived products had the strongest mitigation
      benefits over several decades. Carbon cycle impacts of bioenergy depend on
      timeframe, feedstocks, and alternative uses of biomass, and cannot be assumed
      carbon neutral.

PMID- 30182169
TI  - Correction to: Type 2 Immunity: Methods and Protocols.
AB  - Correction to: R. Lee Reinhardt (ed.), Type 2 Immunity: Methods and Protocols,
      Methods in Molecular Biology, vol. 1799, https://doi.org/10.1007/978-1-4939-7896
      0.

PMID- 30182170
TI  - Characteristics of methotrexate-induced stroke-like neurotoxicity.
AB  - Intrathecal administration of methotrexate (IT-MTX) can lead to neurotoxicity.
      MTX-induced neurotoxicity occasionally manifests with a stroke-like presentation
      that is difficult to distinguish from genuine stroke. We retrospectively reviewed
      records of nine patients with leukemia or lymphoma and episodes of stroke-like
      presentation at our institute between 2010 and 2015 for whom magnetic resonance
      imaging (MRI) data were available. Coagulation test results were compared between
      the two diagnostic groups. Four patients were diagnosed with MTX-induced stroke
      like neurotoxicity. The first neurological event occurred 10-13 days after the
      fourth or later IT-MTX treatment. All four patients had hemiparalysis, two
      exhibited disturbed consciousness and three presented with speech disorders.
      Fibrin/fibrinogen degradation products (FDP) and D-dimer values were within
      normal ranges. MRI revealed bilateral lesions with restricted diffusion in all
      four cases. Neurological symptoms fluctuated and resolved within 5 days, and IT
      MTX was subsequently re-initiated in all four cases. One patient developed
      transient hemiparalysis after a subsequent IT-MTX treatment, but this did not
      recur thereafter. Bilateral lesions on MRI and normal coagulation are indicative
      of MTX-induced stroke-like neurotoxicity. Continuation of IT-MTX after these
      events is generally feasible, but adverse event risk should be carefully weighed
      against anti-tumor benefits.

PMID- 30182171
TI  - KIF20A, highly expressed in immature hematopoietic cells, supports the growth of
      HL60 cell line.
AB  - A microtubule-associated motor protein, kinesin-like family member 20A (KIF20A;
      also called MKlp2) is required for cytokinesis and contributes to intracellular
      vesicular trafficking. KIF20A plays a critical role in the development of several
      cancers, but its role in blood cells and hematological malignancies have not been
      studied. In the present study, we focused on the role of KIF20A in hematopoietic
      cells and possible involvement in myeloid neoplasms. We found that human leukemia
      cell lines and normal bone marrow CD34-positive cells stimulated by growth
      factors, but not mature peripheral blood cells, exhibit high KIF20A expression.
      We further found that HL60 cells, which originally express a large amount of
      KIF20A, showed decreased KIF20A expression in parallel with both neutrophil-like
      and macrophage-like differentiation-induction. KIF20A-knockdown using a
      lentivirus shRNA transfection system led to partial cell cycle arrest at the G2/M
      phase and frequent appearance of multinucleated cells. Treatment with a KIF20A
      selective inhibitor, paprotrain enhanced the multinuclearity of KIF20A-knockdown
      cell clones and suppressed growth. The present study contributes to our
      understanding of the role of KIF20A in blood cells and leukemia cells in
      particular.

PMID- 30182172
TI  - A preliminary study of the relation between IL-4 and hypertension in type II
      diabetes mellitus.
AB  - Clinical outcome of T2DM can be influenced by a polymorphism of different
      cytokines. The aim of this study was to evaluate the effect of genetic variation
      and gene expression of IL-4 in T2DM patients. This study was carried out on type
      II diabetic patients and healthy people served as controls. All subjects were
      submitted to estimation of IL-4 gene polymorphism using VNTR PCR method and gene
      expression by real-time PCR. There was a significant decrease of IL-4 gene
      expression and serum IL4 levels in subjects with B2B2 genotypes. A significant
      positive correlation was found between IL-4 gene expression and the HDL-c levels
      and negative correlation between serum IL4 levels and LDLc. Also, a negative
      correlation was found between serum IL4 and gene expression with both systolic
      and diastolic blood pressure levels in patients group. It can be concluded that
      IL-4 gene expression and serum IL4 reduction in patients with B2B2 genotypes has
      a relation to dyslipidemia and hypertension in the patient with type 2 diabetes
      mellitus.

PMID- 30182173
TI  - Genetic characteristics of the P1 coding region of Coxsackievirus A16 associated
      with hand, foot, and mouth disease in China.
AB  - Coxsackievirus A16 (CVA16) is one of the major etiological agents of hand, foot,
      and mouth disease (HFMD) in young children. To investigate the genetic
      characteristics of the P1 coding region gene of CVA16 associated with HFMD in
      China, we included the sequences of CVA16 specimens obtained from outbreak
      investigations and sporadic HFMD cases between 1998 and 2014 in China from
      GenBank, we genotyped the CVA16 sequences and analyzed P1 coding region sequences
      that encode structural proteins with bioinformatics software. CVA16 was
      classified into genotypes A and B1 based on the VP1 gene; the B1b and B1a
      subgenotypes were the major CVA16 strains and predominated in the coastal areas
      of China. Four strains were found to show inter- and intra-typic recombination in
      the P1 region. The amino acid identities of VP1, VP2, VP3, and VP4 proteins in
      all Chinese CVA16 strains were 88.2-100%, 83.0-100%, 87.6-100%, and 72.4-100%,
      respectively. A total of 251 amino acid substitution sites were detected in the
      structural proteins encoded by the P1 coding region gene. The amino acid
      sequences of the P1 coding region in Chinese CVA16 strains were highly conserved,
      although some amino acid mutations occurred with high frequency: VP1-T11A (10%),
      N14S (14%), L23M/V (11%), T98M (16%), V107A (14%), N102D (6.1%), E145V (8.8%),
      N218D (10%), E241K (22%), T248A/I (6.8%); VP2-I217V (22%), T226A (38%); VP3
      N141S/G (5.4%), and N240D (15%). The genetic characteristics of CVA16 in the P1
      coding region gene may provide a basis for developing a CVA16 vaccine and
      preventing and controlling HFMD in China.

PMID- 30182174
TI  - A Charter to Improve Patient Care in Severe Asthma.
AB  - : Severe asthma is a subtype of asthma that is difficult to treat and control. By
      conservative estimates, severe asthma affects approximately 5-10% of patients
      with asthma worldwide. Severe asthma impairs patients' health-related quality of
      life, and patients are at risk of life-threatening asthma attacks. Severe asthma
      also accounts for the majority of health care expenditures associated with
      asthma. Guidelines recommend that patients with severe asthma be referred to a
      specialist respiratory team for correct diagnosis and expert management. This is
      particularly important to ensure that they have access to newly available
      biologic treatments. However, many patients with severe asthma can suffer
      multiple asthma attacks and wait several years before they are referred for
      specialist care. As global patient advocates, we believe it is essential to raise
      awareness and understanding for patients, caregivers, health care professionals,
      and the public about the substantial impact of severe asthma and to create
      opportunities for improving patient care. Patients should be empowered to live a
      life free of symptoms and the adverse effects of traditional medications (e.g.,
      oral corticosteroids), reducing hospital visits and emergency care, the loss of
      school and work days, and the constraints placed on their daily lives. Here we
      provide a Patient Charter for severe asthma, consisting of six core principles,
      to mobilize national governments, health care providers, payer policymakers, lung
      health industry partners, and patients/caregivers to address the unmet need and
      burden in severe asthma and ultimately work together to deliver meaningful
      improvements in care. FUNDING: AstraZeneca.

PMID- 30182175
TI  - Comment on "Estimating the Bioconcentration Factors of Hydrophobic Organic
      Compounds from Biotransformation Rates Using Rainbow Trout Hepatocytes" by
      Trowell et al. in AECT.

PMID- 30182176
TI  - [Postoperative opioids, endocrine changes,and immunosuppression].

PMID- 30182177
TI  - The Influence of Short-term Fasting on Muscle Growth and Fiber Hypotrophy
      Regulated by the Rhythmic Expression of Clock Genes and Myogenic Factors in Nile
      Tilapia.
AB  - Circadian clock genes and myogenic factors are tightly integrated to influence
      muscle growth upon dietary deprivation in animals. In this study, we reported
      that upon short-term fasting of Nile tilapia juveniles for 7 and 15 days, the
      growth of the fish stagnated and the size of muscle fibers decreased. To reveal
      the molecular mechanisms of how starvation affects fish muscle growth, we
      analyzed the rhythmic expression of circadian clock genes and myogenic factors.
      After 7 and 15 days of fasting treatment, the muscle tissues were collected for
      24 h (at zeitgeber times ZT0, ZT3, ZT6, ZT9, ZT12, ZT18, ZT21, and ZT24) from
      tilapia juveniles. Among the 27 clock genes, the expression of cyr1b, nr1d1,
      per1, clocka, clockb, ciarta, and aanat2 displayed a daily rhythmicity in normal
      daily cycle, while arntl2, cry1a, cry1b, npas2, nr1d2b, per2, per3, roralphab,
      clocka, clockb, nfil3, cipca, and cipcb exhibited daily rhythmicity in the
      fasting fish muscles. The transcript levels of clockb showed moderate positive
      correlation with the aanat2, ciarta, cry1b, and nr1d1 in the muscle tissue of
      normally fed Nile tilapia juvenile. In comparison of the two treatment modes, the
      expression levels of clocka, clockb, and cry1b showed the rhythmicity, but clockb
      expression was significantly decreased and the acrophase had shifted. The
      transcript levels of fbxo32 and pdk4 had either moderate or strong positive
      correlations with other daily expression of clock genes except arntl2 in the
      muscle after 7-day fasting. The expressions of myogenic regulatory factors were
      also either upregulated or downregulated. These observations demonstrated that
      dietary starvation might affect fish muscle growth by modulating the differential
      expression of circadian clock genes and myogenic factors. Thus, our work provides
      a better understanding of the molecular mechanism of dietary starvation on fish
      growth and may provide dietary administration in aquiculture.

PMID- 30182178
TI  - [Primary soft tissue management in open fracture].
AB  - OBJECTIVE: Debridement of soft tissue and bone in an open fracture situation to
      minimize infection risk and achieve primary skin closure, or to provide
      conditions for early soft tissue coverage. INDICATIONS: Indications are Gustilo
      Anderson grade I-III A-C open fractures. CONTRAINDICATIONS: Contraindications are
      injuries requiring amputation, burns, and life-threatening injuries which make
      appropriate treatment temporarily impossible. SURGICAL TECHNIQUE: Removal of
      gross contamination and macroscopic contaminants; debridement of the wound;
      complete resection of contaminated and dirty tissue; sparse step-by-step
      resection of contaminated or non-vital wound and bone margins until vital,
      bleeding tissue begins; low-pressure irrigation with isotonic irrigation fluid;
      diagnostic biopsies for microbiological testing; reduction of dead space by
      interpositioning of muscle or cement spacers loaded with local antibiotics;
      primary wound closure if tension-free closure possible; otherwise, if resources
      and knowhow permit and satisfactory clean debridement was achieved, local flap;
      if flap impossible, debridement not satisfactory, secondary tissue necrosis
      likely, potential remaining contamination or contamination with fecal matter,
      then vacuum-assisted closure therapy. POSTOPERATIVE MANAGEMENT: Wound inspection
      on the second postoperative day, generous indication for second-look surgery
      after 36-48 h, wound inspection on the second postoperative day, wound inspection
      every other day, primary antibiotic prophylaxis with a first- or second
      generation cephalosporin (e. g., cefuroxime), and adaptation of antibiotic
      therapy according to susceptibility screening. RESULTS: Infection rates of 2-4.7%
      are reported for immediate primary wound closure in Gustilo-Anderson grade I, II,
      and III A open fractures. For Gustilo-Anderson grade III B, good wound healing,
      bony consolidation, and no need for secondary surgery was reported in 86.7% when
      primary wound closure was achieved.

PMID- 30182179
TI  - A review of the ethnopharmacology, phytochemistry, and pharmacology of Changium
      smyrnioides Wolff.
AB  - Changium smyrnioides Wolff is a monotypic species of the genus Changium Wolff
      which is only found in eastern China. C. smyrnioides has been used as a
      traditional medicine for ages to treat cough, vomiting, nausea, megrim, and
      carbuncle. It is also widely used to brew medicated liquor and health tea with
      other herbs in order to moisten the lungs and nourish blood and yin. This review
      comprehensively summarizes the up-to-date information on the botanical
      characterization, distribution, traditional uses, ethnopharmacology,
      phytochemistry, pharmacology, and toxicity of C. smyrnioides based on studies
      published in recent years. Phytochemical investigations have revealed that
      phenylpropanoids, volatile oils, fatty acids, phytosterols, and other bioactive
      compounds are contained in C. smyrnioides. Crude extracts and monomeric compounds
      isolated from C. smyrnioides have significant effects on the respiratory, immune,
      and vascular systems and exhibit favourable activities such as antitussive,
      eliminating phlegm, anti-asthmatic, immunoregulatory, antioxidant, anti-tumor,
      anti-fatigue, anti-hypoxia, and anti-atherosclerotic effects. C. smyrnioides is a
      promising medicinal herb with immense therapeutic and health-promoting effects.
      Therefore, further studies on the bioactive compounds and mechanisms of C.
      smyrnioides are necessary. Additional clinical and toxicological studies are
      warranted to evaluate its safety.

PMID- 30182180
TI  - New depsidone and dichromone from the stems of Garcinia paucinervis with
      antiproliferative activity.
AB  - A new depsidone, paucinervin Q (1), a new dichromone, paucinervin R (2), and a
      known compound, paucinervin B (3), were isolated from the stems of Garcinia
      paucinervis by various chromatographic methods. Their structures were determined
      by analysis of spectroscopic data. The isolates were evaluated for their
      antiproliferative activity against three cancer cell lines HL-60, PC-3 and CaCo
      2. Compound 1 showed significant inhibitory activities.

PMID- 30182181
TI  - A rare clinical presentation: a pleomorphic xanthoastrocytoma presenting with
      intracerebral haemorrhage and metastasizing vigorously-case report and review of
      the literature.
AB  - Metastasis of an intracranial tumour is not a common situation in our daily
      neurosurgical practice. Pleomorphic xanthoastrocytoma is also a rare glial tumour
      with relatively a favourable prognosis among other CNS pathologies. Here, we
      present an anaplastic pleomorphic xanthoastrocytoma case which shows both
      haematogenous and lymphatic metastasis which is described first time in the up-to
      date literature. Our case is a 17-year-old male operated for a right occipital
      intra-axial lesion with a diagnosis of anaplastic pleomorphic xanthoastrocytoma
      which recurs 5 years later and metastasize vigorously through haematogenous and
      lymphatic routes. A rare-presenting symptom for this pathology is also
      intracerebral haemorrhage. This is the ninth case report in the literature which
      presents initially with this entity.

PMID- 30182182
TI  - Treatment of Atopic Dermatitis with Biologic Drugs.
AB  - Atopic dermatitis (AD) is a chronic, pruritic, inflammatory skin disease which
      predominately affects children and usually clears up during infancy or childhood.
      However, AD may persist with a chronic relapsing course until adulthood or
      develop at a later age. AD treatment can often be complicated. Treating moderate
      to-severe AD can be challenging: only a few therapeutic options are available,
      with cyclosporine being the only approved and labeled systemic drug. In the last
      few years, advances in the knowledge of AD pathogenesis have been made that can
      provide the basis for developing new topical and systemic drugs. Among them,
      biologic drugs targeting specific cytokines involved in the development of the
      disease will probably revolutionize AD therapy. Currently, dupilumab, a
      monoclonal antibody that binds to the shared alpha chain subunit of the receptors
      for IL-4 and IL-13, is the only biologic drug licensed for the treatment of AD in
      adults. However, other biologic drugs that selectively target some key cytokines
      in AD pathogenesis (IL-13, IL-31, and IL-22) are also being studied. In this
      review, we discuss all of the biologic drugs that have been studied for AD
      treatment.

PMID- 30182183
TI  - Women's knowledge, attitude and practice related to urinary incontinence:
      systematic review.
AB  - INTRODUCTION: Knowledge, attitude and practice (KAP) investigations lead to an
      understanding of what a particular population group knows, thinks and does in
      relation to a certain subject. METHODS: This systematic review was conducted to
      identify women's KAP related to urinary incontinence (UI) described in the
      literature and the measurement/evaluation instruments used. A literature search,
      up to July 2017, was conducted in PUBMED, SCOPUS and BVS (Virtual Health Library)
      for articles dealing with women's KAP related to UI that described the validation
      procedure of any data collection instrument. Articles that investigated
      exclusively male subjects, provider performance or academic teaching strategies
      were excluded. Relevant studies were analyzed and briefly summarized. RESULTS:
      Initially, 799 articles were retrieved. After applying the inclusion and
      exclusion criteria, 19 remained for reading and summarizing. There has been
      interest in identifying and evaluating some of the KAP elements related to UI
      since 1994, with a wide variety of validated instruments used. Knowledge was
      evaluated in 15 articles and all concluded that there was misinformation about UI
      in the populations studied. Seven articles studied the intention to seek
      healthcare for UI, among which only one evidenced an adequate attitude in more
      than 70% of the participants. All the articles that investigated practice
      revealed low rates of seeking care. CONCLUSIONS: The KAP elements are influenced
      by specific questions in each of the studied populations, leading to unique
      results, which indicates the importance of investigations using standardized data
      collection instruments that have psychometric validity tested in the target
      populations.

PMID- 30182184
TI  - Preventive treatment with dizocilpine attenuates oedema in a carrageenan model of
      inflammation: the interaction of glutamatergic and nitrergic signaling.
AB  - Dizocilpine is a highly selective and potent non-competitive antagonist of the N
      methyl-D-aspartate (NMDA) glutamate receptor. It is well known that dizocilpine
      has different neuroprotective effects in animal models of pain, epilepsy and
      oedema during trauma. The search for alternative antiinflammatory drugs is
      ongoing. We investigated the anti-oedematous effects of dizocilpine and the
      probable mechanism of action in a rat model that mimics local and persistent
      inflammation without tissue injury or damage. Male Wistar rats were injected with
      100 MUL of 0.5% carrageenan to the plantar surface of the hind paw. Anti
      oedematous activity was assessed in the carrageenan-induced paw inflammatory
      oedema test with a plethysmometer. To assess possible mechanisms of dizocilpine
      action, we examined the effects of the selective inhibitor of neuronal [N-omega
      propyl-L-arginine hydrochloride (L-NPA)] and inducible [S-methylisothiourea
      (SMT)] nitric oxide synthase (NOS). Dizocilpine after systemic (0.0005, 0.005 and
      0.02 mg/kg, subcutaneous (s.c.)), but not after local peripheral administration,
      reduced the paw inflammatory oedema. The effect is not dose dependent, and the
      highest decrease by about 47% at the time of maximally developed oedema was
      achieved with 0.005 mg/kg. Intraperitoneally (i.p.) administered L-NPA (0.5, 1
      and 2 mg/kg) or SMT (0.005, 0.01 and 0.015 mg/kg) before dizocilpine abolished or
      reduced the anti-oedematous effect of dizocilpine by about 70-85%. An acute
      single dose of dizocilpine administered before inducing oedema systemically
      reduced the development of inflammatory oedema. The mechanism of the anti
      oedematous effect includes, at least partially, an increase in nitric oxide (NO)
      production.

PMID- 30182185
TI  - Age-related reversal of spinal excitability during anticipatory postural control.
AB  - INTRODUCTION: An internal perturbation of standing balance activates muscles
      critical for maintaining balance and is preceded by anticipatory postural
      adjustments (APAs). In healthy younger adults, a measure of spinal excitability
      in the form of the Hoffmann (H) reflex becomes depressed during APAs but how
      aging affects the reflex control of APAs is unknown. METHODS: We compared H
      reflex excitability profiles in the right soleus muscle, indirectly indicating
      APA, between younger (n = 11, age 19-24 years), middle-aged (n = 10, age 37-56
      years), and older healthy adults (n = 11, age 63-78 years). Subjects rapidly
      raised the right-dominant arm in response to an auditory cue. The H reflex was
      evoked 120 ms, 100 ms, 80 ms, 60 ms, 40 ms, 20 ms, and 0 ms before as well as 20
      ms after the onset of the right anterior deltoid muscle activation. For data
      processing, each trial was controlled for the corresponding background EMG
      activity before normalizing the standing data to the data in sitting in the 8
      time bins. RESULTS: All subjects showed a silent period in the soleus background
      electromyographic activity, suggesting the presence of APA. We found that the
      stereotypical H reflex depression associated with APAs in younger adults was
      reduced in middle-aged adults and reversed to facilitation in older adults. The
      depression occurred in 10 out of 11 younger adults, whereas all 11 older adults
      exhibited facilitation. CONCLUSION: Because APAs are organized at the supraspinal
      level, we speculate a supraspinal origin of the age-related reflex facilitation
      during APAs.

PMID- 30182187
TI  - [Painful to the touch, subcutaneous tumor on the palm of the hand].

PMID- 30182186
TI  - A phenomenological model of the time course of maximal voluntary isometric
      contraction force for optimization of complex loading schemes.
AB  - PURPOSE: The time course of maximal voluntary isometric contraction (MVIC) force
      is of particular interest whenever force capacities are a limiting factor, e.g.,
      during heavy manual work or resistance training (RT) sessions. The objective of
      this work was to develop a mathematical model of this time course that is
      suitable for optimization of complex loading schemes. MATERIALS AND METHODS: We
      compiled a literature overview of existing models and justified the need for a
      new model. We then constructed a phenomenological ordinary differential equation
      model to describe the time course of MVIC force during voluntary isometric
      contractions and at rest. We validated the model with a comprehensive set of
      published data from the elbow flexors. For this, we estimated parameters from a
      subset of the available data and used those estimates to predict the remaining
      data. Afterwards, we illustrated the benefits of our model using the calibrated
      model to (1) analyze fatigue and recovery patterns observed in the literature (2)
      compute a work-rest schedule that minimizes fatigue (3) determine an isometric RT
      session that maximizes training volume. RESULTS: We demonstrated that our model
      (1) is able to describe MVIC force under complex loading schemes (2) can be used
      to analyze fatigue and recovery patterns observed in the literature (3) can be
      used to optimize complex loading schemes. CONCLUSIONS: We developed a
      mathematical model of the time course of MVIC force that can be efficiently
      employed to optimize complex loading schemes. This enables an optimal use of MVIC
      force capacities.

PMID- 30182188
TI  - Atorvastatin ameliorates the contractile dysfunction of the aorta induced by
      organ culture.
AB  - Statins are widely used in the treatment of hypercholesterolemia. Studies have
      demonstrated that statins could maintain vascular contractile function through
      inhibiting the transformation of vascular smooth muscle cells (VSMCs) from the
      contractile phenotype to the synthetic phenotype. However, the underlying
      mechanisms have not been fully elucidated. The effect of atorvastatin on the
      thoracic aorta of Sprague-Dawley rats cultured in serum-free conditions in vitro
      was evaluated. Aortic constriction was induced by high potassium, phenylephrine,
      and CaCl2. The protein expression levels of alpha1 adrenoceptor; inositol 1,4,5
      trisphosphate (IP3) receptor; protein kinase Cdelta (PKCdelta); stromal
      interaction molecule 1 (STIM1); high-voltage activated dihydropyridine-sensitive
      (L type, Cav1.2) channels; and two contractile phenotype marker proteins [alpha
      smooth muscle actin (alpha-SMA) and myosin (SM-MHC)] were determined by western
      blotting. Compared with the fresh control, the constriction of rat aorta was
      impaired after culture in serum-free medium for 24 h. The impaired contraction of
      cultured aortas was mediated by Cav1.2 and store-operated Ca2+ (SOC) channel,
      which could be improved by atorvastatin at 20 MUM. The protein expression levels
      of alpha1 adrenoceptor, IP3 receptor, PKCdelta, STIM1, Cav1.2, alpha-SMA, and SM
      MHC in the aortas cultured in serum-free conditions were decreased significantly.
      Atorvastatin partially prevented the reduction in the contractility and the
      downregulation of these proteins in cultured aortas. The transformation of the
      VSMC phenotype is associated with the vasoconstriction dysfunction of cultured
      aortas. Atorvastatin may protect vascular function by modulating calcium
      signaling pathways.

PMID- 30182189
TI  - Enhanced production of poly(3-hydroxybutyrate) in recombinant Escherichia coli
      and EDTA-microwave-assisted cell lysis for polymer recovery.
AB  - Poly(3-hydroxybutyrate) (PHB) is a bacterial polymer of great commercial
      importance due to its properties similar to polypropylene. With an aim to develop
      a recombinant system for economical polymer production, PHB biosynthesis genes
      from Bacillus aryabhattai PHB10 were cloned in E. coli. The recombinant cells
      accumulated a maximum level of 6.22 g/L biopolymer utilizing glycerol in shake
      flasks. The extracted polymer was confirmed as PHB by GC-MS and NMR analyses. The
      polymer showed melting point at 171  degrees C, thermal stability in a
      temperature range of 0-140  degrees C and no weight loss up to 200  degrees C.
      PHB extracted from sodium hypochlorite lysed cells had average molecular weight
      of 143.108 kDa, polydispersity index (PDI) 1.81, tensile strength of 14.2 MPa and
      an elongation at break of 7.65%. This is the first report on high level polymer
      accumulation in recombinant E. coli solely expressing PHB biosynthesis genes from
      a Bacillus sp. As an alternative to sodium hypochlorite cell lysis mediated
      polymer extraction, the effect of combined treatment with
      ethylenediaminetetraacetic acid and microwave was studied which attained 93.75%
      yield. The polymer recovered through this method was 97.21% pure, showed 2.9-fold
      improvement in molecular weight and better PDI. The procedure is simple, with
      minimum polymer damage and more eco-friendly than the sodium hypochlorite lysis
      method.

PMID- 30182190
TI  - Risk of endometrial cancer in asymptomatic postmenopausal patients with thickened
      endometrium: data from the FAME-Endo study: an observational register study.
AB  - PURPOSE: To evaluate the risk for endometrial cancer (EC) in a large series of
      asymptomatic patients with thickened endometrium at ultrasound examination based
      on previously published data of a theoretical cohort. METHODS: In a prospective
      register study, a total of 1024 women with thickened endometrium in ultrasound
      examination undergoing histological diagnosis by dilation, hysteroscopy and
      curettage were evaluated. 124 patients were excluded due to current medication
      with tamoxifen and/or presence of HNPCC leaving 900 patients for further
      analysis. RESULTS: Mean [standard deviation (SD)] age of patients was 65.6 (8.6)
      years. Mean (SD) endometrial thickness was 11.9 (5.8) mm. 32 and 6 cases of EC
      and complex endometrial hyperplasia with atypia were found, respectively. In the
      univariate analysis, a statistically significant association between endometrial
      thickness, current use of antihypertensive medication, number of deliveries, and
      the presence of endometrial fluid in preoperative vaginal ultrasound (p < 0.05)
      with EC was found. A multivariate logistic regression model incorporating these
      parameters showed a statistically significant independent association of
      endometrial thickness, number of deliveries, and the presence of endometrial
      fluid in preoperative vaginal ultrasound (p < 0.05), but not current use of
      antihypertensive medication, with EC. Using a cut-off of the endometrial
      thickness of > 11 mm, the risk for "EC alone" and "EC and complex endometrial
      hyperplasia with atypia combined" was found to be 6.7% and 7.9%, respectively.
      CONCLUSIONS: Our data compare favorably to a theoretical cohort suggesting a
      clinically reasonable cut-off of > 11 mm endometrial thickness to discriminate
      between "normal" and "pathological". The data regarding "risk for endometrial
      cancer" can be used for counseling affected women.

PMID- 30182191
TI  - The first line of defence: insights into mechanisms and relevance of phagocytosis
      in epithelial cells.
AB  - Epithelial tissues cover most of the external and internal surfaces of the body
      and its organs. Inevitably, these tissues serve as first line of defence against
      inorganic, organic, and microbial intruders. Epithelial cells are the main cell
      type of these tissues. Besides their function as cellular barrier, there is
      growing evidence that epithelial cells are of particular relevance as initial
      sensors of danger and also as executers of adequate defence responses. These
      cells feature various essential functions to maintain tissue integrity in health
      and disease. In this review, we survey some of the different innate immune
      functions of epithelial cells in mucosal tissues being constantly exposed to a
      plethora of harmless contaminants but also of pathogens. We discuss how
      epithelial cells avoid inadequate immune responses in such conditions. In
      particular, we will focus on the diverse types and mechanisms of phagocytosis
      used by epithelial cells to not only maintain homeostasis but to also harness the
      host response against invading pathogens.

PMID- 30182192
TI  - [Baroreflex activation therapy : Indication and evidence in resistant
      hypertension and heart failure].
AB  - Baroreflex activation therapy (BAT) is a sympathoinhibitory procedure for
      treatment of therapy-resistant hypertension (rsHTN) and severe heart failure with
      reduced ejection fraction (HFrEF) that been available for several years. The
      double-blind, randomized Rheos Pivotal Trial demonstrated a blood pressure
      lowering effect in patients with rsHTN for the first-generation BAT device. A
      smaller randomized study in heart failure showed that the Barostim Neo system is
      safe and can improve heart failure symptoms and decrease neuroendocrine
      activation. However, for this unilateral system, which is currently in clinical
      use, no data from large randomized trials exist. Despite existing data for BAT in
      rsHTN and HFrEF, large randomized trials, showing reduction of blood pressure and
      cardiovascular events are still lacking. Therefore, BAT's efficacy and safety
      cannot be conclusively assessed.

PMID- 30182193
TI  - [Catheter-based atrial appendage closure-current data and future developments].
AB  - In Germany more than 1.6 million patients suffer from atrial fibrillation (AF).
      Within the next decades this number will substantially increase due to current
      demographic trends with the increasing average age of the population. When
      untreated, patients with atrial fibrillation have a five times higher risk for
      stroke as compared with a control cohort. A potent stroke prevention therapy
      reducing the risk of stroke by approximately 70-80% is primarily treatment with
      new oral anticoagulants (NOACs). The risk scores for stroke (CHA2DS2-VASc) and
      major bleeding (HAS-BLED) in patients with atrial fibrillation share common
      variables, so that patients with the highest stroke risk often carry a very high
      bleeding risk. A significant number of patients (ca. 20-30%) are, however, not
      eligible for long-term anticoagulation, e.g. because of a high bleeding risk. For
      this population there is an urgent need for alternative stroke prevention
      strategies, such as catheter-based percutaneous left atrial appendage closure.
      Current data about the efficiency and safety of this treatment as well as a
      discussion of ongoing recruitment for randomized studies are discussed in this
      review.

PMID- 30182195
TI  - Retraction Note to: Overexpression of a cotton annexin gene, GhAnn1, enhances
      drought and salt stress tolerance in transgenic cotton.
AB  - The authors are retracting this article because irregularities were involved in
      the reuse of stomatal images in Figure 9.

PMID- 30182196
TI  - Coping with High Temperature: A Unique Regulation in A. tumefaciens.
AB  - Elevation of temperature is a frequent and considerable stress for mesophilic
      bacteria. Therefore, several molecular mechanisms have evolved to cope with high
      temperature. We have been studying the response of Agrobacterium tumefaciens to
      temperature stress, focusing on two aspects: the heat-shock response and the
      temperature-dependent regulation of methionine biosynthesis. The results indicate
      that the molecular mechanisms involved in A. tumefaciens control of growth at
      high temperature are unique and we are still missing important information
      essential for understanding how these bacteria cope with temperature stress.

PMID- 30182194
TI  - The ethylene response factor MdERF1B regulates anthocyanin and proanthocyanidin
      biosynthesis in apple.
AB  - KEY MESSAGE: The regulator MdERF1B in the apple (Malus * domestica) ethylene
      pathway mainly acts on MdMYB9 and MdMYB11 to regulate anthocyanin and
      proanthocyanidin accumulation. Dietary anthocyanins and proanthocyanidins (PAs)
      have health benefits for humans, and are associated with decreased risks of
      coronary heart disease and cancer. Ethylene can enhance reddening of apple (Malus
      * domestica), but the regulatory mechanism is poorly understood. In this study,
      an ethylene response factor (ERF), MdERF1B, was identified and functionally
      characterized. 'Orin' calli overexpressing MdERF1B were generated and then
      analyzed by quantitative reverse transcription-PCR. Compared with the control
      calli, the MdERF1B-overexpressing calli showed increased expression levels of
      MdACO1, MdERF1, and MdERF3 in the ethylene pathway and MdCHS, MdCHI, MdF3H,
      MdDFR, MdANS, MdLAR, MdANR, MdMYB9 and MdMYB11 in the flavonoid pathway. As a
      result, the levels of anthocyanins and PAs were significantly increased in the
      MdERF1B-overexpressing calli. MdERF1B interacted with MdMYB9, MdMYB1, and MdMYB11
      proteins in yeast two-hybrid, pull-down, and bimolecular fluorescence
      complementation assays. Furthermore, in yeast one-hybrid and electrophoretic
      mobility shift assays, MdERF1B also bound to the promoters of MdMYB9, MdMYB1, and
      MdMYB11. In a luciferase reporter assay, MdERF1B mainly activated proMdMYB9 and
      proMdMYB11, promoting their expression levels. This was in agreement with
      MdERF1B's overexpression in calli, which barely affected MdMYB1 expression. Taken
      together, our findings provide an insight into the regulatory mechanisms in the
      ethylene pathway that increase anthocyanin and PA accumulation in apple.

PMID- 30182197
TI  - Real-Time Trafficking of Agrobacterium Virulence Protein VirE2 Inside Host Cells.
AB  - A. tumefaciens delivers T-DNA and virulence proteins, including VirE2, into host
      plant cells, where T-DNA is proposed to be protected by VirE2 molecules as a
      nucleoprotein complex (T-complex) and trafficked into the nucleus. VirE2 is a
      protein that can self-aggregate and contains targeting sequences so that it can
      efficiently move from outside of a cell to the nucleus. We adopted a split-GFP
      approach and generated a VirE2-GFP fusion which retains the self-aggregating
      property and the targeting sequences. The fusion protein is fully functional and
      can move inside cells in real time in a readily detectable format: fluorescent
      and unique filamentous aggregates. Upon delivery mediated by the bacterial type
      IV secretion system (T4SS), VirE2-GFP is internalized into the plant cells via
      clathrin adaptor complex AP2-mediated endocytosis. Subsequently, VirE2-GFP binds
      to membrane structures such as the endoplasmic reticulum (ER) and is trafficked
      within the cell. This enables us to observe the highly dynamic activities of the
      cell. If a compound, a gene, or a condition affects the cell, the cellular
      dynamics shown by the VirE2-GFP will be affected and thus readily observed by
      confocal microscopy. This represents an excellent model to study the delivery and
      trafficking of an exogenously produced and delivered protein inside a cell in a
      natural setting in real time. The model may be used to explore the theoretical
      and applied aspects of natural protein delivery and targeting.

PMID- 30182198
TI  - Effect of Nano-SiO2 on Expression and Aberrant Methylation of Imprinted Genes in
      Lung and Testis.
AB  - Nanotechnology has been developing rapidly and is now used in many cutting-edge
      medical therapeutics. However, there is increasing concern that exposure to
      nanoparticles (NPs) may induce different systemic diseases as epigenetic
      mechanisms are associated with more and more disease. The role of NP epigenomic
      modification is important to disease etiology. Our study aimed to determine the
      epigenetic mechanisms of damage in lung and testis cells by exposing cells to
      SiO2 NPs. We used male C57BL/6 mice to characterize the damaging effect of SiO2
      NPs on lung and testis cells as well as the resulting methylation state at the
      imprinted Dlk1/Dio3 domain region. The A549 cells exposed to SiO2 NPs had cell
      apoptosis, and male mice exposed to SiO2 NPs had altered lung and testis tissues.
      The genes in the imprinted domains Dlk1/Dio3 region changed in both tissues;
      Dlk1, Rtl1, and Dio3 are upregulated in testis while Dlk1 and Dio3 are also
      upregulated in lung tissues. Bisulfite sequencing PCR of male adult lung and
      testis were mostly hypomethylated, with a few hypermethylated CpGs. These
      findings indicate that nanoparticles play an important role in DNA methylation of
      imprinted genes.

PMID- 30182199
TI  - Up-regulated lipocalin-2 in pediatric thyroid cancer correlated with poor
      clinical characteristics.
AB  - BACKGROUND: The incidence of thyroid cancer is fast increasing in both adults and
      children. The pediatric thyroid cancer had often already progressed to a more
      advanced stage of the disease at diagnosis. Early detection of pediatric thyroid
      cancer has been a problem for many years. Lipocalin-2 (Lcn2) has been reported to
      be over-expressed in cancers of diverse histological origin and it facilitates
      tumorigenesis by promoting survival, growth, and metastasis. METHODS: The plasma
      Lcn2 concentration of 28 Chinese papillary thyroid cancer (PTC) children and 24
      healthy controls was measured. Immunostaining for Ki-67 of tumor tissue from PTC
      children was performed. The expression levels of Lcn2 and NFkappaB in PTC tissue
      and peri-carcinoma tissue of PTC children were measured through Western blot.
      RESULTS: The plasma concentration of Lcn2 was significantly elevated in pediatric
      PTC patients compared with healthy controls. Besides, the plasma Lcn2
      concentration significantly correlated with clinical characteristics, NFkappaB
      level, and Ki-67 positive rate of nucleus in tissue of PTC. CONCLUSION: This is
      the first study to evaluate the plasma Lcn2 in pediatric PTC patients. It is
      possible that the plasma Lcn2 may be a new biomarker of pediatric thyroid cancer.
      Further studies are needed to explore the definite role and mechanism of Lcn2 in
      thyroid cancer, which will help to explore novel diagnostic or therapeutic
      strategies.

PMID- 30182200
TI  - Modeling the spatially varying risk factors of dengue fever in Jhapa district,
      Nepal, using the semi-parametric geographically weighted regression model.
AB  - Dengue fever is expanding rapidly in many tropical and subtropical countries
      since the last few decades. However, due to limited research, little is known
      about the spatial patterns and associated risk factors on a local scale
      particularly in the newly emerged areas. In this study, we explored spatial
      patterns and evaluated associated potential environmental and socioeconomic risk
      factors in the distribution of dengue fever incidence in Jhapa district, Nepal.
      Global and local Moran's I were used to assess global and local clustering
      patterns of the disease. The ordinary least square (OLS), geographically weighted
      regression (GWR), and semi-parametric geographically weighted regression (s-GWR)
      models were compared to describe spatial relationship of potential environmental
      and socioeconomic risk factors with dengue incidence. Our result revealed
      heterogeneous and highly clustered distribution of dengue incidence in Jhapa
      district during the study period. The s-GWR model best explained the spatial
      association of potential risk factors with dengue incidence and was used to
      produce the predictive map. The statistical relationship between dengue incidence
      and proportion of urban area, proximity to road, and population density varied
      significantly among the wards while the associations of land surface temperature
      (LST) and normalized difference vegetation index (NDVI) remained constant
      spatially showing importance of mixed geographical modeling approach (s-GWR) in
      the spatial distribution of dengue fever. This finding could be used in the
      formulation and execution of evidence-based dengue control and management program
      to allocate scare resources locally.

PMID- 30182201
TI  - Machine learning: applications of artificial intelligence to imaging and
      diagnosis.
AB  - Machine learning (ML) is a form of artificial intelligence which is placed to
      transform the twenty-first century. Rapid, recent progress in its underlying
      architecture and algorithms and growth in the size of datasets have led to
      increasing computer competence across a range of fields. These include driving a
      vehicle, language translation, chatbots and beyond human performance at complex
      board games such as Go. Here, we review the fundamentals and algorithms behind
      machine learning and highlight specific approaches to learning and optimisation.
      We then summarise the applications of ML to medicine. In particular, we showcase
      recent diagnostic performances, and caveats, in the fields of dermatology,
      radiology, pathology and general microscopy.

PMID- 30182203
TI  - More on Age of Onset of Attractions and Sexual Development in Pedohebephilic
      Individuals: Response to Tozdan and Briken (2018).

PMID- 30182204
TI  - Know Thy Gender: Etymological Primer.

PMID- 30182202
TI  - Tuning ion channel mechanosensitivity by asymmetry of the transbilayer pressure
      profile.
AB  - Mechanical stimuli acting on the cellular membrane are linked to intracellular
      signaling events and downstream effectors via different mechanoreceptors.
      Mechanosensitive (MS) ion channels are the fastest known primary mechano
      electrical transducers, which convert mechanical stimuli into meaningful
      intracellular signals on a submillisecond time scale. Much of our understanding
      of the biophysical principles that underlie and regulate conversion of mechanical
      force into conformational changes in MS channels comes from studies based on MS
      channel reconstitution into lipid bilayers. The bilayer reconstitution methods
      have enabled researchers to investigate the structure-function relationship in MS
      channels and probe their specific interactions with their membrane lipid
      environment. This brief review focuses on close interactions between MS channels
      and the lipid bilayer and emphasizes the central role that the transbilayer
      pressure profile plays in mechanosensitivity and gating of these fascinating
      membrane proteins.

PMID- 30182205
TI  - "Telephone Scatologia": Onomasiological and Historical Note.

PMID- 30182206
TI  - Exploring Pain Management Among Asian Immigrants with Chronic Pain: Self
      Management and Resilience.
AB  - Asians immigrants (AIs) are one of the fastest growing racial groups in many
      countries globally. Despite pain prevalence, studies on chronic pain management
      among AIs is limited in the literature. An integrative review was conducted
      exploring the current state of science on chronic pain management among AIs.
      Several databases were used to identify related articles and 15 studies met the
      inclusion criteria. Two major themes emerged: (a) self-management, pertaining to
      how AIs take responsibility for their pain, and (b) resilience, their adaptive
      behaviors indicating low levels of pain-related dysfunction and burden despite
      chronic pain severity. Resilience plays a significant role in the mechanism by
      which self-management works in pain among AIs. Chronic pain management is a
      complex process where challenges to effective treatments exist. Findings have
      significant implications to healthcare providers and the general pain population.
      Future research directions include the necessity for increased participation of
      AIs in studies.

PMID- 30182207
TI  - InAs/GaAs Quantum Dot Dual-Mode Distributed Feedback Laser Towards Large Tuning
      Range Continuous-Wave Terahertz Application.
AB  - In this paper, a laterally coupled distributed feedback (LC-DFB) laser based on
      modulation p-doped multiple InAs/GaAs quantum dot (QD) structures has been
      fabricated. The device exhibits a high side-mode suppression ratio (SMSR) of > 47
      dB and a high thermal stability of dlambda/dT = 0.092 nm/K under continuous-wave
      (CW) operation, which is mainly attributed to the high material gain prepared by
      modulation p-doping and rapid thermal annealing (RTA) process, and the
      significantly reduced waveguide losses by shallow-etched gratings and its close
      proximity to the laser ridge feature in the LC-DFB laser. With this superior
      performance of the DFB laser, the wide tunable dual-wavelength lasing operation
      has been obtained by delicately defining different periods for the grating
      structures on the two sides of the laser ridge or combining the reduced laser
      cavity length. The wavelength spacing between the two lasing modes can be
      flexibly tuned in a very wide range from 0.5 to 73.4 nm, corresponding to the
      frequency difference from 0.10 to 14 THz, which is the largest tuning range by
      the utilization of single device and hence providing a new opportunity towards
      the generation of CW THz radiation.

PMID- 30182208
TI  - Relapse patterns in patients with local and regional cutaneous melanoma.
AB  - BACKGROUND: The differences in features and risk factors for recurrence after
      definitive surgical excision are yet to be determined. The aim of this study was
      to understand these factors influencing recurrence patterns with local and
      regional disease in these patients. METHODS: A total of 365 relapsed patients, of
      whom 196 presented with local disease (stage I-II) and 169 with regional disease
      (stage III), were investigated in this retrospective study. RESULTS: The median
      time to initial recurrence for stage I-II and stage III patients was 22.3 and
      13.4 months, respectively. Stage III patients were found to have higher Clark
      levels (p = 0.0001) and thicker lesions (p = 0.0001), and they were more
      significantly associated with the absence of tumor-infiltrating lymphocytes (p =
      0.02) than stage I-II patients. Stage III patients were more significantly
      associated with recurrences compared to the stage I-II patients (p = 0.0001).
      Locoregional relapses were significantly associated with stage I-II melanomas,
      whereas majority of the distant metastases occurred in stage III patients (p =
      0.01). Pulmonary metastasis was most frequently observed and the distribution of
      the sites for distant metastases was similar in both groups of the patients. On
      univariate analysis, male sex, increased tumor depth, presence of ulceration,
      nodular histopathology, higher Clark level, higher mitotic rate, and presence of
      lymphovascular invasions were found to predict shorter time to relapse for stage
      I-II patients; whereas only nodular pathology, presence of ulceration, and high
      mitotic rate were found to be associated with poor relapse-free survival in stage
      III patients. However, on multivariate analysis, only mitotic rate maintained its
      significance for both clinical staging groups. CONCLUSION: Potential differences
      among early-stage melanoma patients, who developed recurrence, were noted and
      mitotic rate was found as the single significant prognostic factor for recurrence
      in both stage I-II and III patients.

PMID- 30182209
TI  - Impact of diabetes comorbidity on the efficacy and safety of FOLFOX first-line
      chemotherapy among patients with metastatic colorectal cancer: a pooled analysis
      of two phase-III studies.
AB  - BACKGROUND: The current analysis aims to provide an evaluation of the impact of
      diabetes mellitus (DM) on the efficacy and safety of first-line FOLFOX
      chemotherapy for patients with metastatic colorectal cancer (mCRC). METHODS: This
      is a pooled analysis of the comparator arms of two clinical trials (NCT00272051;
      NCT00305188) which evaluated first-line FOLFOX chemotherapy for patients with
      mCRC. The overall survival and progression-free survival according to patient
      subsets (non-diabetic and diabetic patients) were assessed through Kaplan-Meier
      analysis and log-rank testing. Propensity score matching was additionally
      conducted to account for heterogeneity in baseline characteristics of different
      subsets of patients. RESULTS: A total of 756 patients were enrolled in the
      current analysis; of which 64 patients have pre-existing DM while 692 patients
      were non-diabetic. Through Kaplan-Meier analysis, no evidence for overall or
      progression-free survival difference was found among the two patient subsets (P =
      0.501; P = 0.960, respectively). Moreover, metformin treatment does not affect
      overall or progression-free survival among diabetic patients (P = 0.598; P =
      0.748, respectively). Repetition of overall and progression-free survival
      assessment following propensity score matching does not reveal any differences.
      Comparing diabetic to non-diabetic patients, there were no differences between
      the two groups in terms of acute oxaliplatin-induced neurological symptoms
      including cold-induced dysthesia (P = 0.600), laryngeal dysthesia (P = 0.707),
      jaw pain (P = 0.743) or muscle pain (P = 0.506). Moreover, no difference was seen
      between the two groups in terms of the incidence of long-term oxaliplatin-induced
      paresthesia (P = 0.107), highest grade of paresthesia (P = 0.498) or rates of
      recovery from paresthesia (P = 0.268). Diabetic patients have, however, a shorter
      time to develop oxaliplatin-induced paresthesia (P = 0.024). CONCLUSION: DM does
      not seem to affect overall or progression-free survival of mCRC patients treated
      with first-line FOLFOX chemotherapy. Moreover, DM does not influence the
      incidence or severity of oxaliplatin-induced paresthesia in those patients while
      it might lead to a shorter time to develop oxaliplatin-induced paresthesia
      compared to non-diabetic patients.

PMID- 30182210
TI  - Beyond first-line systemic treatment for metastatic urothelial carcinoma of the
      bladder.
AB  - Metastatic urothelial carcinoma of the bladder is a rarely curable disease.
      Patients receive systemic therapy with limited response rates and survival
      benefits. The rescue regimens of these patients who have failed first-line
      treatment had remained problematic until the recent advances. Several trials with
      novel regimens, including immune checkpoint inhibitors and targeted therapy, to
      salvage relapsed urothelial carcinoma of the bladder have recently been
      published. However, the choice of an optimal treatment regimen remains
      challenging in the absence of randomized trials comparing regimen sequences.
      Daily clinical cases provoke the question of whether there is a preferred second
      line regimen. This paper provides an overview of recent trials and proposes a
      management algorithm based on subgroup analyses and prognostic features.

PMID- 30182211
TI  - Retroperitoneal fibrosis secondary to non-urology carcinomas: a clinical and
      outcome analysis of 97 cases.
AB  - PURPOSE: Accumulated evidences have reminded us that since the prognosis of
      retroperitoneal fibrosis (RPF) secondary to non-urology carcinoma is poor it is
      essential to distinguish this condition from others. The objective of this study
      is to investigate the clinical features and outcomes of this infrequent but life
      threatening disease. METHODS: A total of 97 patients diagnosed with RPF secondary
      to non-urology carcinoma were enrolled in this retrospective study. The baseline
      information, history of carcinoma, clinical presentation, laboratory results,
      diagnosis, treatment and prognosis of the patients were collected and analyzed.
      RESULTS: The mean age was 62.32 +/- 11.22 years (range 31-85 years). It took
      16.72 +/- 7.11 days (range 3-34 days) for the patients with originally
      unexplained hydronephrosis to get a definite diagnosis of RPF secondary to non
      urology carcinoma. Imaging-confirmed RPF [confirmed by computed tomography (CT)
      or magnetic resonance imaging (MRI)] was found in 91 patients. Fifty-seven
      patients were diagnosed with histological-confirmed malignant RPF. Sixty-six
      patients received surgical interventions. Cystoscopy and double J tube were
      performed in 68 cases (102 sides, 172 times) and was failed in 93 times (54.07%).
      Pyelostomy was performed in 72 patients (92 sides) without a single failure.
      Furthermore, eighty patients received chemotherapy and/or radiotherapy. The 6
      month survival since RPF secondary to non-urology carcinoma was confirmed was
      30%. CONCLUSIONS: All patients with newly diagnosed unexplained hydronephrosis
      should undergo an age-appropriate carcinoma screening. The prognosis of RPF
      secondary to non-urology carcinoma was dismal. When dealing with hydronephrosis
      affecting renal function, pyelostomy instead of double J tube catheterization
      should be performed ahead of time.

PMID- 30182212
TI  - Inhibiting 6-phosphogluconate dehydrogenase enhances chemotherapy efficacy in
      cervical cancer via AMPK-independent inhibition of RhoA and Rac1.
AB  - BACKGROUND: The oxidative pentose phosphate pathway (PPP) is essential for cancer
      metabolism and growth. However, the contribution of 6-phosphogluconate
      dehydrogenase (6PGD), a key enzyme of PPP, to cervical cancer development remains
      largely unknown. METHODS: mRNA and protein levels of 6PGD were analyzed in
      cervical cancer cells and tissues derived from patients and compared to normal
      counterparts. Using cell culture system and xenograft mouse model, the functions
      of 6PGD in cervical cancer are determined and its molecular mechanism is
      analyzed. 6PGD inhibitor physcion and siRNA knockdown were used. RESULTS: In this
      work, we demonstrate that 6PGD is aberrantly upregulated and activated in
      cervical cancer cells and patient tissues compared to normal counterparts. Using
      different approaches and preclinical models, we show that 6PGD inhibition
      decreases growth and migration, and enhances chemosensitivity in cervical cancer.
      Mechanistically, inhibition of 6PGD activates AMP-activated protein kinase (AMPK)
      and decreases RhoA and Rac1 activities. AMPK depletion significantly reduces the
      effects of 6PGD inhibition in decreasing RhoA and Rac1 activities, growth and
      migration in cervical cancer cells. CONCLUSIONS: Our work is the first to
      demonstrate the aberrant expression of 6PGD and its predominant roles in cervical
      cancer cell growth and migration, via a AMPK-dependent activation. Our findings
      suggest 6PGD as a potential therapeutic target to enhance chemosensitivity in
      cervical cancer.

PMID- 30182213
TI  - Emergency Radiology: its first 25 years: accomplishments to celebrate.

PMID- 30182214
TI  - On Some Possible Ramifications of the "Microplastics in Fish" Case.
AB  - Cases of research misconduct in the ecological and environmental sciences appear
      to be relatively rare. A controversial paper published in Science in 2016
      documenting the effects of microplastics on the feeding and innate behaviours of
      fish larvae has recently been retracted, with the authors found guilty of
      scientific misconduct. In addition to the expected fallout, such as individual
      and institutional reputational damage from a research misconduct finding, this
      case has two possibly wider-ranging ramifications. Firstly, there may be a
      presumptive notion that a strong negative effect could be more successfully
      published than a neutral effect. This presumption would belie the true stringency
      and rigor of research adopted by workers in the field. Secondly, the case may
      have a negative impact on the public's perception of and trust in legitimate and
      good science that addresses critical environmental issues, such as anthropogenic
      climate change.

PMID- 30182215
TI  - From nutraceutical to clinical trial: frontiers in Ganoderma development.
AB  - Ganoderma spp. are medical mushrooms with various pharmacological compounds which
      are regarded as a nutraceutical for improving health and treating diseases. This
      review summarizes current progress in the studies of Gamoderma ranging from
      bioactive metabolites, bioactivities, production techniques to clinical trials.
      Traditionally, polysaccharides and ganoderic acids have been reported as the
      major bioactive metabolites of Ganoderma possessing anti-tumor and
      immunomodulation functions. Moreover, recent studies indicate that Gandoerma also
      exerts other bioactivities such as skin lighting, gut microbiota regulation, and
      anti-virus effects. However, since these medical fungi are rare in natural
      environment, and that the cost of cultivation of fruiting bodies is high,
      industrial submerged fermentation of Ganoderma mycelia promotes the development
      of Ganoderma by dint of an increase of biomass and bioactive metabolites used for
      further application. In addition, various strategies for production of different
      metabolites are well developed, such as gene regulation, bi-stage pH, and oxygen
      control. To date, Ganoderma not only has become one of the most popular
      nutraceuticals worldwide but also has been applied to clinical trials for
      advanced diseases such as breast and non-small-cell lung cancer.

PMID- 30182216
TI  - Infant posture and movement analysis using a sensor-supported gym with toys.
AB  - Infant posture and motor pattern development are normally analyzed by clinical
      assessment scales. Lately, this approach is combined with the use of sensor
      supported systems, such as optical, inertial, and electromagnetic measurement
      systems, as well as novel assessment devices, such as CareToy. CareToy is a
      modular device for assessment and rehabilitation of preterm infants, comprising
      pressure mattresses, inertial and magnetic measurement units, and sensorized
      toys. Since such integrated sensor system combination is new to the field of
      sensor-supported infant behavior assessment and rehabilitation, dedicated methods
      for data analysis were developed and presented. These comprise trunk rotation,
      arm movement, forearm orientation, and head movement analysis, along with toy
      play and trunk posture stability evaluation. Methods were tested on case study
      data, evaluating suitability of developed algorithms for infant posture and
      activity analysis, regardless of behavioral responses. Obtained results
      demonstrate suitability of the proposed methods for successful use in studies of
      different motor pattern subfields. This represents an important step on the
      course towards objective, accurate, sensor-supported infant motor development
      assessment. Graphical abstract Posture and movement assessment of infants using
      analysis of sensory data, obtained with a dedicated sensorized gym with toys.

PMID- 30182217
TI  - Effects of the arterial radius and the center-line velocity on the conductivity
      and electrical impedance of pulsatile flow in the human common carotid artery.
AB  - In order to investigate the contribution of arterial radius and center-line
      velocity to the blood conductivity and electrical impedance of pulsatile flow in
      the human common carotid artery, we proposed three simplified mathematical models
      to describe the relationship between the center-line velocity, the arterial
      radius, and the blood conductivity. By comparing the fitting results with those
      obtained from our previously proposed elastic-tube hemodynamic model, we found
      that the change in center-line velocity had more notable effect on the blood
      conductivity than the change in arterial radius. Moreover, the change in arterial
      radius contributed much more to the electrical impedance than the change in blood
      conductivity induced by the center-line velocity. Graphical abstract Graphical
      abstract contains poor-quality text inside the artwork. Please do not re-use the
      file that we have rejected or attempt to increase its resolution and re-save. It
      is originally poor; therefore, increasing the resolution will not solve the
      quality problem. We suggest that you provide us the original format. We prefer
      replacement figures containing vector/editable objects rather than embedded
      images. Preferred file formats are eps, ai, tiff and pdf.The new graphical
      abstract have been attached. ?.

PMID- 30182220
TI  - A New Species of Szeptyckitheca (Collembola, Symphypleona, Sphyrothecinae) from
      Brazil.
AB  - A new species of the genus Szeptyckitheca is described from the Biological
      Reserve of Serra do Japi, Sao Paulo State, Brazil. All species of the genus
      present trochanteral spine on the first and third legs, cephalic chaeta A1 often
      absent. The presence of spine in all trochanters, chaetal row F in head, and
      abdominal and antennal segments with long bristles with capitate apex are
      relevant features that distinguishes the new species from all known species of
      the genus. A key to the identification of the species of Szeptyckitheca is
      presented.

PMID- 30182218
TI  - Are adolescents really being sedentary or inactive when at school? An analysis of
      sedentary behaviour and physical activity bouts.
AB  - This study analysed physical activity (PA) and sedentary behaviour (SB) performed
      in bouts during schooltime. Adolescents of two schools answered a questionnaire,
      had their height and weight measured and wore accelerometers during schooltime.
      Moderate-to-vigorous intensity PA was estimated in bouts of 2, 5 and 10 min, and
      SB in bouts of 5, 10, 30 and 60 min. Body mass index was calculated, and
      adolescents were classified as overweight or normal weight. Frequency, duration
      and volume of PA and SB were calculated for the whole sample and for those who
      performed at least one bout weekly. PA and SB differences between gender and
      weight status were tested using Mann-Whitney and t tests. A total of 415
      adolescents (54% girls, 12.3 +/- 1.3 years old, 34.6% overweight) performed 0.1
      (+/- 0.2), 0.2 (+/- 0.5) and 0.4 (+/- 0.6) bouts of 10, 5 and 2 min of PA, and
      10.6 (+/- 2.0), 6.0 (+/- 1.3), 1.1 (+/- 0.9) and 0.4 (+/- 0.5) bouts/day of 5,
      10, 30 and 60 min of SB, respectively. Boys accumulated less SB and more PA in
      bouts. No differences were found for weight status.Conclusion: Adolescents hardly
      engaged in bouted PA and accumulated more SB in smaller bouts during schooltime.
      Bouted PA and SB were not associated with weight status. What is Known: *
      Adolescents are not engaging in enough PA and are accumulating large volumes of
      SB, which might negatively impact their health. * Schools play an important role
      in daily overall PA, with opportunities such as PE classes and recesses. But most
      classes are still undertaken in seated positions. What is New: * Adolescents
      hardly engage in bouted (> 10 m) PA when at school., and most SB is accumulated
      in short bouts (<=  10m). * Weight status was not associated with bouted PA or SB
      at school.

PMID- 30182219
TI  - A single-arm, phase II trial of neoadjuvant gemcitabine and S1 in patients with
      resectable and borderline resectable pancreatic adenocarcinoma: PREP-01 study.
AB  - BACKGROUND: Neoadjuvant chemotherapy (NAC) represents a promising alternative to
      pancreatic ductal adenocarcinoma (PDAC) planned resection, but the survival
      impact remains undefined. To assess the feasibility and survival outcomes of NAC
      with gemcitabine and S1 (GS) for PDAC planned resection by prospective study.
      METHODS: Patients with resectable or borderline resectable PDAC received 2 cycles
      of NAC-GS and were offered curative resection followed by gemcitabine adjuvant.
      The primary endpoint was 2-year overall survival (OS). Adverse events during NAC,
      radiological and tumor marker responses, resection rate, and surgical safety were
      evaluated as secondary endpoints (UMIN000004148). RESULTS: We enrolled 104
      patients between 2010 and 2012, with 101 patients treated using NAC-GS as the
      full analysis set (FAS). Of the 101 patients, 88% received the planned 2 cycles
      of NAC. Grade 3 neutropenia was common (35%). Radiological partial response and
      decreased carbohydrate antigen 19-9 concentration (> 50% decrease) were noted in
      13% and 41%, respectively. R0/1 resections with M0 were performed in 65 patients
      without surgical mortality. Of the 65 patients, 44 received planned gemcitabine
      adjuvant for 6 months as the on-protocol cohort. The primary endpoint for the 2
      year OS rate was 55.9% in the FAS (n = 101) and 74.6% in the on-protocol cohort
      (n = 44). CONCLUSIONS: NAC-GS was feasible and actively prolonged survival
      following PDAC planned resection. Randomized control trials are needed to further
      clarify the survival benefit of NAC-GS in addition to surgery followed by
      adjuvant therapy.

PMID- 30182221
TI  - Characteristics of the portal vein thrombosis recurrence pattern without liver
      parenchymal invasion from colorectal cancer: a case report.
AB  - BACKGROUND: Portal vein tumor thrombosis from colorectal cancer is rare, and this
      recurrence pattern was mainly reported in patients with renal cell carcinoma and
      hepatocellular carcinoma. Furthermore, the recurrence pattern of portal vein
      tumor thrombosis without liver parenchymal invasion from colorectal carcinoma has
      not been previously reported. Herein, we present a patient with progressive
      portal vein tumor thrombosis without liver parenchymal invasion following
      curative resection. CASE PRESENTATION: A 61-year-old man with a chief complaint
      of constipation with abdominal pain associated with rectal carcinoma was admitted
      to our hospital. Computed tomography (CT) showed that the rectosigmoid colon wall
      was thickened, regional lymph nodes were swollen, and the light space-occupying
      lesion (SOL) was detected at segment 8 (S8). Neoadjuvant chemotherapy was
      performed, which was followed by laparoscopic anterior resection. The final
      diagnosis was stage IIIb (SS, N2, M0). After operation, systemic adjuvant
      chemotherapy was introduced. At first, tumor marker levels were within the normal
      range and there were no accumulations on positron emission tomography (PET).
      Tumor marker levels were elevated, and contrast-enhanced CT demonstrated that the
      portal vein SOL slowly extended from S8 to S5. Additionally, PET showed that the
      standardized uptake value was abnormally high at 5.8. Based on the diagnosis of
      portal vein tumor thrombosis, right hepatectomy was performed. On pathological
      analysis, tumor thrombosis was associated with rectal carcinoma, and there was no
      invasion toward the liver parenchyma. Additionally, the surgical cut end was
      tumor free. Six months after the hepatectomy, the paraaortic lymph nodes showed
      swelling. The patient is currently undergoing systemic chemotherapy. CONCLUSION:
      Aggressive surgical resection should be considered in cases of portal vein tumor
      thrombosis. A good long-term prognosis could be obtained by a combination of
      curative resection and systemic chemotherapy.

PMID- 30182222
TI  - Pacemaker-associated thrombosis in ongoing therapy with edoxaban tosylate.
AB  - Thromboembolism is a known complication of pacemaker implantation. However,
      published literature describes only a few cases, in which the events occurred in
      absence of antithrombotic prophylaxis, not routinely employed for its prevention
      in current clinical practice. We report a case of pacemaker lead-associated
      thrombosis in a patient taking continuative oral anticoagulant therapy with
      edoxaban tosylate (edoxaban). No data in present literature supports the use of
      anticoagulant prophylaxis for pacemaker lead thrombosis. In our report ongoing
      treatment with edoxaban proved ineffective for thrombosis prevention. We also
      discuss the role of three-dimensional transthoracic echocardiography for
      diagnostic assessment of thrombosis in a fragile patient.

PMID- 30182223
TI  - Safety and effectiveness of long-term use of darbepoetin alfa in non-dialysis
      patients with chronic kidney disease: a post-marketing surveillance study in
      Japan.
AB  - BACKGROUND: This post-marketing surveillance (PMS) study evaluated the safety and
      effectiveness of long-term darbepoetin alfa (darbepoetin) for the treatment of
      renal anemia in Japanese non-dialysis chronic kidney disease patients. METHODS:
      Patients were treated with darbepoetin and followed up for 3 years. Adverse
      events (AEs), adverse drug reactions (ADRs), hemoglobin (Hb) levels, and renal
      function were assessed. Patients were stratified by Hb level at the time of
      occurrence of cardiovascular-related AEs. Statistical analyses were performed to
      explore factors affecting the occurrence of AEs, cardiovascular-related AEs, and
      composite renal endpoints. RESULTS: In the safety analysis set (5547 patients),
      AEs and ADRs occurred in 44.4 and 7.1% of patients, respectively. Cardiovascular
      related AEs were observed in 12.6% of the overall population. The proportion of
      patients who presented cardiovascular-related AEs was lower among those with a
      higher Hb level at the time of occurrence. In the effectiveness analysis set
      (5024 patients), mean Hb levels remained between 10.0 and 10.6 g/dL (Weeks 4
      156). Three months after darbepoetin administration, patients with Hb >= 11 g/dL
      presented fewer composite renal endpoints than those with Hb < 11 g/dL (p =
      0.0013), and the cumulative proportion of renal survival was higher in those with
      Hb >= 11 g/dL vs. Hb < 11 g/dL (p < 0.0001). CONCLUSIONS: This PMS study showed
      the safety and effectiveness of long-term use of darbepoetin in a large number of
      patients. Patients with Hb >= 11 g/dL presented fewer composite renal endpoints
      than those with Hb < 11 g/dL, without an increase in the incidence of
      cardiovascular-related AEs.

PMID- 30182224
TI  - Quantifying Re-association of a Facultative Endohyphal Bacterium with a
      Filamentous Fungus.
AB  - We present here a method to quantify reassociation between facultative endohyphal
      bacteria and filamentous fungal hosts. Our method takes advantage of the
      capabilities of fungal cell walls to selectively protect internal bacteria from
      gentamicin treatment, an assay adapted from studies of internalized bacterial
      pathogens in cell culture. We report the efficacy of gentamicin to kill
      planktonic bacteria treated during fungal coculture, and also describe and
      characterize a sampling scheme to recover and quantify culturable bacteria from
      the growing edge of fungal mycelium in vitro. This assay enables qualitative and
      quantitative tests of reassociation capabilities for facultative endohyphal
      bacteria with host fungi and provides a means to investigate the genetic basis
      for these associations in a repeatable way.

PMID- 30182225
TI  - Characterizing Mycoviruses.
AB  - A variety of methods for the detection and characterization of fungal viruses are
      available. For many years, serological and biological assays were used for virus
      detection. Today, more sensitive methods like polymerase chain reaction, together
      with sequencing, are widely used to study viruses. Extracting double-stranded
      (ds) RNA can be a useful approach to detect and study mycoviruses from fungal
      tissues, as dsRNAs accumulate in infected cells as copies of viral genomes or as
      replicative intermediates of single-stranded RNA genomes. Here we present a basic
      protocol for growing fungal strains and isolating dsRNA using cellulose
      chromatography, followed by molecular diagnostic methods including cDNA
      synthesis, sequencing, and determination of 5' ends by primer ligation.

PMID- 30182226
TI  - Analysis of Secondary Metabolites from Plant Endophytic Fungi.
AB  - Filamentous fungi produce a wide variety of secondary metabolites, which are
      recognized as a rich source of biomolecules with potential medicinal
      applications. According to chemical structures and biosynthetic pathways,
      secondary metabolites are mainly divided into four groups, including polyketide,
      nonribosomal peptides, alkaloids, and terpenes. Owing to their special living
      environment, plant endophytic fungi potentially produce many bioactive
      metabolites with diverse structural features. Some of these metabolites have been
      demonstrated to hold pharmaceutical and ecological significance. In order to
      identify bioactive compounds, different methods have been developed to isolate
      secondary metabolites from plant endophytic fungi. In this chapter, we describe
      the procedures for fungal fermentation, metabolite extraction, and analysis using
      high-performance liquid chromatography (HPLC). The endophytic fungus
      Pestalotiopsis fici, which was isolated from the healthy branches of Camellia
      sinensis (Theaceae), produces 88 secondary metabolites including 70 new natural
      products. Combining 74 secondary metabolite clusters revealed by genome
      sequencing analysis, P. fici is used as an example for analysis of secondary
      metabolites. The procedures could also be adopted for other fungi after small
      modifications.

PMID- 30182227
TI  - Protocols for Investigating the Leaf Mycobiome Using High-Throughput DNA
      Sequencing.
AB  - High-throughput sequencing of taxon-specific loci, or DNA metabarcoding, has
      become an invaluable tool for investigating the composition of plant-associated
      fungal communities and for elucidating plant-fungal interactions. While
      sequencing fungal communities has become routine, there remain numerous potential
      sources of systematic error that can introduce biases and compromise
      metabarcoding data. This chapter presents a protocol for DNA metabarcoding of the
      leaf mycobiome based on current best practices to minimize errors through careful
      laboratory practices and validation.

PMID- 30182228
TI  - Characterizing Small RNAs in Filamentous Fungi Using the Rice Blast Fungus,
      Magnaporthe oryzae, as an Example.
AB  - The goal of this chapter is to provide a framework of sequential steps for small
      RNA (sRNA) analysis in filamentous fungi. Here, we present protocols for (1)
      comparative analysis of sRNAs in different conditions, (2) comparisons of sRNA
      libraries to RNAseq data and (3) identification and analysis of methylguanosine
      capped and polyadenylated sRNAs (CPA-sRNAs). This species of small RNA is
      particularly interesting in Magnaporthe oryzae, as they map to transcription
      start and end sites of protein-coding genes. While we do not provide specific
      command lines for scripts, we provide a general framework for steps needed to
      carry out all three types of analyses, including relevant references, websites
      and free online tools. Screenshots are provided from our own customized interface
      using M. oryzae as an example, to assist the reader in visualizing many of the
      steps.

PMID- 30182229
TI  - Plant Small RNAs Responsive to Fungal Pathogen Infection.
AB  - Accumulating evidence indicates that small noncoding RNAs (sRNAs) can be
      transferred across species for interkingdom communication. In addition to the
      artificial transgene-derived small interfering RNAs (siRNAs), endogenous
      microRNAs (miRNAs) can also influence interacting organisms to execute a
      regulatory function. For instance, we have recently found that, in response to
      infection with Verticillium dahliae (V. dahliae), cotton plants increase
      accumulation of miR166 and miR159, which can be exported to the fungal hyphae for
      specific silencing of virulence genes. These findings suggest a great potential
      for applying interkingdom mobile miRNAs for crop protection against fungal
      pathogens. The methods described here provide an approach to identify plant
      miRNAs and their potential targets in invading fungal pathogens, which will help
      in revealing the underlying mechanisms of these crosstalk phenomena.

PMID- 30182230
TI  - Sequential Phosphopeptide Enrichment for Phosphoproteome Analysis of Filamentous
      Fungi: A Test Case Using Magnaporthe oryzae.
AB  - A number of challenges have to be overcome to identify a complete complement of
      phosphorylated proteins, the phosphoproteome, from cells and tissues.
      Phosphorylated proteins are typically of low abundance and moreover, the
      proportion of phosphorylated sites on a given protein is generally low. The
      challenge is further compounded when the tissue from which protein can be
      recovered is limited. Global phosphoproteomics primarily relies on efficient
      enrichment methods for phosphopeptides involving affinity binding coupled with
      analysis by fast high-resolution mass spectrometry (MS) and subsequent
      identification using various software packages. Here, we describe an effective
      protocol for phosphopeptide enrichment using an Iron-IMAC resin in combination
      with titanium dioxide (TiO2) beads from trypsin digested protein samples of the
      filamentous fungus Magnaporthe oryzae. Representative protocols for LC-MS/MS
      analysis and phosphopeptide identification are also described.

PMID- 30182231
TI  - Assays for MAP Kinase Activation in Magnaporthe oryzae and Other Plant Pathogenic
      Fungi.
AB  - Mitogen-activated protein (MAP) kinases have the hallmark motif TXY and function
      in key signal transduction pathways in eukaryotic organisms. Most ascogenous
      plant pathogenic fungi have three MAPK pathways that regulate different
      developmental and infection processes. In the rice blast fungus Magnaporthe
      oryzae, the Pmk1 and Mps1 MAP kinases with the TEY motif are essential for
      appressorium formation, penetration, and invasive growth. Osm1 is the third MAP
      kinase that has the TGY motif and functions in osmoregulation. Although orthologs
      of Pmk1 and Mps1 are important for pathogenesis in all the plant pathogens
      studied, Osm1 orthologs have species-specific roles in stress responses and
      pathogenesis. Because of their functions in fungal development and pathogenesis,
      it is important to determine the expression and activation of MAP kinases under
      different growth conditions or infection stages. In this chapter, we describe
      methods for protein extraction and detection of the activation of the three MAP
      kinases in M. oryzae with the commercially available anti-TpEY or anti-TpGY
      phosphorylation-specific antibodies. Similar approaches can be used to monitor
      MAP kinase activation in other plant pathogenic fungi.

PMID- 30182232
TI  - Visualizing the Movement of Magnaporthe oryzae Effector Proteins in Rice Cells
      During Infection.
AB  - During biotrophy, filamentous pathogens such as the rice blast fungus Magnaporthe
      oryzae deliver effector proteins into live host cells to facilitate colonization.
      We describe three complementary assays for visualizing M. oryzae effector
      translocation into the rice cytoplasm and cell-to-cell movement during infection.
      Our assays make use of live-cell confocal imaging of optically clear rice sheath
      cells infected with transgenic strains of M. oryzae that express the fluorescent
      protein-tagged effector known as PWL2. We highlight several important
      considerations for the analysis of effector translocation and movement dynamics
      during infection of host plants.

PMID- 30182233
TI  - Illuminating Phytophthora Biology with Fluorescent Protein Tags.
AB  - Phytophthora species cause diseases that threaten agricultural, ornamental, and
      forest plants worldwide. Explorations of the biology of these pathogens have been
      aided by the availability of genome sequences, but much work remains to decipher
      the roles of their proteins. Insight into protein function can be obtained by
      visualizing them within cells, which has been facilitated by recent improvements
      in fluorescent protein and microscope technologies. Here, we describe strategies
      to permit investigators to generate strains of Phytophthora that express
      fluorescently tagged proteins and study their localization during growth in
      artificial media and during plant infection.

PMID- 30182234
TI  - Methods for Transient Gene Expression in Wild Relatives of Potato.
AB  - Genomics studies in potato and other plants have elucidated a large number of
      genes involved in a wide array of phenotypes. In particular, recent bioinformatic
      and genomic analyses of oomycetes and fungi have identified many effectors for
      which the corresponding host resistance-eliciting receptor remains to be found.
      Functional testing of host resistance gene candidates can be accomplished by
      generating whole plant transformants to either overexpress or silence these genes
      to obtain a visible phenotype. However, this is time consuming. Alternatively,
      Agrobacterium tumefaciens can be used to transiently express genes in plant
      tissue to observe phenotypic changes. Wild relatives of potato contain a large
      amount of genotypic diversity and are an excellent tool to identify important
      agronomic traits, including resistance to diseases. The methods presented here
      help to facilitate the screening of wild potato accessions using
      agroinfiltration.

PMID- 30182235
TI  - Host-Induced Gene Silencing (HIGS) for Elucidating Puccinia Gene Function in
      Wheat.
AB  - Biotrophic fungi (Puccinia spp.) cause devastating diseases of wheat and other
      cereal species globally. The function of large repertories of genes from Puccinia
      spp. still needs to be discovered to understand the infection process of these
      obligate parasites, eventually to protect plants from rust diseases. Functional
      analysis of targeted genes is challenging due to the inherent difficulties with
      culturing the fungus and transforming the host. RNA interference (RNAi) is a
      conserved gene regulation process in eukaryotes and known to be a powerful
      genetic tool in plant biotechnology. More recently, host-induced gene silencing
      (HIGS) has been developed to assess pathogen gene function in plants. HIGS is an
      RNAi-based process where double stranded RNA (dsRNA) homologous to a pathogen
      gene can be expressed in a plant to induce targeted silencing of the pathogen
      gene. Here we described a detailed HIGS protocol for functional analysis of rust
      genes from Puccinia species in cereals. As an example we describe an experiment
      silencing the tryptophan 2-monooxygenase gene (Pgt-IaaM) from Puccinia graminis
      f. sp. tritici (Pgt) that is involved in virulence to wheat.

PMID- 30182236
TI  - From Short Reads to Chromosome-Scale Genome Assemblies.
AB  - A high-quality, annotated genome assembly is the foundation for many downstream
      studies. However, obtaining such an assembly is a complex, reiterative process
      that requires the assimilation of high-quality data and combines different
      approaches and data types. While some software packages incorporating multiple
      steps of genome assembly are commercially available, they may not be flexible
      enough to be routinely applied to all organisms, particularly to nonmodel species
      such as pathogenic oomycetes and fungi. If researchers understand and apply the
      most appropriate, currently available tools for each step, it is possible to
      customize parameters and optimize results for their organism of study. Based on
      our experience of de novo assembly and annotation of several oomycete species,
      this chapter provides a modular workflow from processing of raw reads, to initial
      assembly generation, through optimization, chromosome-scale scaffolding and
      annotation, outlining input and output data as well as examples and alternative
      software used for each step. The accompanying Notes provide background
      information for each step as well as alternative options. The final result of
      this workflow could be an annotated, high-quality, validated, chromosome-scale
      assembly or a draft assembly of sufficient quality to meet specific needs of a
      project.

PMID- 30182237
TI  - BLASTmap: A Shiny-Based Application to Visualize BLAST Results as Interactive
      Heat Maps and a Tool to Design Gene-Specific Baits for Bespoke Target Enrichment
      Sequencing.
AB  - Numerous genes that determine the outcome of plant-pathogen interactions are
      currently being discovered and include, for example, immune receptors,
      susceptibility factors and pathogen effectors and their host targets. Target
      enrichment sequencing provides a means to preferentially resequence these genes
      of interest without the need to first generate a genotype-specific genome
      assembly. The Basic Local Alignment Search Tool (BLAST), in combination with the
      here developed BLASTmap, can be used to design probes that specifically target
      such gene(s), either by using the target species or the closest related genus as
      a reference. BLAST is a ubiquitous tool in biological sequence analysis and a
      multitude of programs are available for the visualization of BLAST alignments.
      However, there are currently no dedicated programs for visual comparison of large
      scale BLAST output attributes such as bit score. The need to quickly and
      efficiently compare many thousands of BLAST results led to the development of
      BLASTmap, an interactive web application created using the Shiny R package,
      customized for clustering and viewing BLAST results as an interactive heat map.
      Here we show an example of how BLASTmap was successfully applied to analyze
      custom DNA/RNA probe sequences and to visually determine that four probes are
      sufficient for the specific yet inclusive enrichment of the potato R2 disease
      resistance gene family.

PMID- 30182238
TI  - A Computational Protocol to Analyze Metatranscriptomic Data Capturing Fungal-Host
      Interactions.
AB  - Plant diseases cause significant losses to agricultural production and pose
      serious threats to food security worldwide. Understanding the mechanism of host
      pathogen interaction is essential for the development of novel diagnostic methods
      and disease management strategies. RNA sequencing (or RNA-Seq) technology enables
      a global characterization and quantification of all transcripts of organisms from
      which RNA can be obtained, and it is particularly useful in identifying pathogen
      virulence factors involved in disease development and host immunity involved in
      the development of resistance. This chapter describes a computational protocol to
      manage, analyze and interpret RNA-Seq data. We have included two transcriptome
      analysis approaches, one reference-guided and the other de novo assembly-based,
      and discuss pros and cons for each method. We have also presented visualization
      methods to generate high quality figures as well as data mining strategies for
      identifying candidate genes/pathways involved in host immunity and pathogen
      virulence. In summary, this protocol captures the fungal-plant interactions at
      the transcriptional level and facilitates rapid gene discovery and expression
      analysis using next-generation sequencing data of mixed host and pathogen
      transcripts (i.e., metatranscriptomics). All bioinformatic tools used to build
      this protocol are publically available, and we strove to make them accessible to
      researchers with limited computational skills and applicable to
      metatranscriptomic data analysis in a wide range of plant-fungal interactions.

PMID- 30182239
TI  - Application of the Cre/lox System to Construct Auxotrophic Markers for
      Quantitative Genetic Analyses in Fusarium graminearum.
AB  - The bacteriophage P1 Cre/lox system has been utilized in diverse fungi for marker
      recycling and exchange, generation of targeted chromosome translocations, and
      targeted deletion of interstitial chromosome segments. Here we show the
      application of this tool in the wheat and maize pathogen, Fusarium graminearum.
      We explored three different ways to introduce Cre into strains with floxed genes,
      namely transformation with an episomal or integrative plasmid (pLC28), fusion of
      protoplasts of strains carrying floxed genes with strains expressing Cre by
      forcing heterokaryons, and crosses between strains with floxed genes and strains
      expressing Cre to isolate progeny in which the target genes had been deleted
      during the cross. We used this system for the construction of strains bearing
      auxotrophic markers that were generated by gene replacement with positively
      selectable markers followed by Cre-mediated marker excision. In addition, updated
      protocols for transformation and crosses for F. graminearum are provided. In
      combination, strains and tools developed here add to the arsenal of methods that
      can be used to carry out molecular genetics with F. graminearum.

PMID- 30182240
TI  - Protocol of Phytophthora capsici Transformation Using the CRISPR-Cas9 System.
AB  - Phytophthora capsici is an important plant pathogen, which causes significant
      economic losses on multiple vegetable crops worldwide. It is an ideal model
      pathogen to study the role of important genes, plant-pathogen interactions, and
      fungicide resistance mechanisms etc. due to its wide range of hosts and genetic
      diversity. A more efficient gene editing tool is required to do these studies.
      Here, we describe a detailed experimental procedure using the CRISPR-Cas9 system
      to edit genes of interest in P. capsici, which has been proven to be an accurate
      and efficient gene editing method in P. capsici.

PMID- 30182241
TI  - Generating Gene Silenced Mutants in Phytophthora sojae.
AB  - Phytophthora species are notorious pathogens of plants and cause enormous damage
      to agriculture. In order to understand Phytophthora pathogenesis, gene silencing
      and knockout methods are important for the investigation of gene functions.
      Although CRISPR/Cas9-based gene knockout procedures have been developed in
      Phytophthora sojae and Phytophthora capsici, it may not always be the best choice
      especially when knockout mutation leads to lethality. Therefore, gene silencing
      is a very useful tool for functional analysis of target genes in Phytophthora.
      This chapter introduces a gene silencing protocol for the soybean pathogen P.
      sojae. An expression cassette is incorporated into the P. sojae genome through
      PEG-mediated protoplast transformation, which leads to constitutive production of
      antisense RNA transcripts. These transcripts are able to target mRNAs through
      sequence complementarity and effectively reduce the expression of the target
      genes.

PMID- 30182245
TI  - Health services research in German radiation oncology: new opportunities to
      advance cancer care.
AB  - BACKGROUND: Health services research (HSR) is of increasing relevance to
      scientists, health-care providers, and clinicians. Complex population-based
      secondary data are a key source of information for analyses of health-care
      effects in radiation oncology. METHODS: In this short paper, we examine potential
      applications of secondary data focusing on statistics from the diagnosis-related
      groups (DRG). This data set incorporating all hospitalized cases in Germany is
      based on claims of reimbursements and is provided by the Research Data Centers
      (RDC) of the Federal Statistical Office and the Statistical Offices of the
      federal states. A short outlook regarding other data sources is also presented.
      RESULTS: In radiation oncology, secondary data such as the DRG statistics have
      rarely been used to examine health-care effects, despite their great potential
      for reporting effects in a broad population-based setting. Furthermore, for most
      data sources, the application to use these data is accessible with minor effort.
      However, data concerning outpatient care are difficult to analyze on a comparable
      level. CONCLUSION: DRG statistics and related secondary data provide a remarkable
      source of information for analyses of health-care-related effects in radiation
      oncology.

PMID- 30182246
TI  - Early and late toxicity profiles of patients receiving immediate postoperative
      radiotherapy versus salvage radiotherapy for prostate cancer after prostatectomy.
AB  - PURPOSE: The present study aims to evaluate both early and late toxicity profiles
      of patients receiving immediate postoperative radiotherapy (RT; adjuvant RT or
      additive RT) compared to salvage RT. METHODS: We evaluated 253 patients with
      prostate cancer treated with either immediate postoperative (adjuvant RT, n = 42;
      additive RT, n = 39) or salvage RT (n = 137). Thirty-five patients received
      salvage treatment but did not achieve a postoperative prostate specific antigen
      (PSA) level <0.1 ng/ml and thus were excluded from analysis. RESULTS: A
      significantly higher rate of early grade 1/2 proctitis in the immediate
      postoperative RT group without additional pelvic RT was observed (p = 0.02).
      Patients in the immediate postoperative RT group without additional pelvic RT
      showed significantly more early urinary tract obstructions (p = 0.003). Toxicity
      rates of early (<3 months) and late (3-6 months) postoperative RT were similar (p
      > 0.05). Baseline recovery rate of erectile dysfunction was better in patients
      with immediate postoperative RT without additional pelvic RT (p = 0.02; hazard
      ratio (HR) = 2.22, 95%-confidence interval, 95%-CI: 1.12-4.37). Recovery rate of
      urinary incontinence showed no significant difference in all groups (p > 0.05).
      CONCLUSION: Patients receiving immediate postoperative RT (adjuvant or additive
      RT) without additional pelvic RT experience early gastrointestinal (GI) side
      effect proctitis and, as well as early genitourinary (GU) toxicity urinary tract
      obstruction more frequently than patients treated with salvage RT. Therefore,
      complete recovery after surgery is essential. However, we suggest basing the
      treatment decision on the patient's postoperative clinical condition and
      evaluation of any adverse risk factors, since many studies demonstrate a clear
      benefit for immediate postoperative RT (adjuvant or additive RT) in terms of
      oncological outcome.

PMID- 30182247
TI  - Treatment of malnutrition decreases complication rates and shortens the length of
      hospital stays in a radiation oncology department.
AB  - PURPOSE: The nutritional status of inpatients influences the therapeutic outcome.
      Malnutrition is a common comorbidity in oncological patients. Both radio- and
      radiochemotherapy may contribute to the additional deterioration of the
      nutritional status. The aim of this study was to evaluate the impact of
      specialized treatment of malnutrition as a clinical routine. METHODS: The
      nutritional status of inpatients was assessed by the Nutritional risk screening
      (NRS-2002) on the day of admission to the University Department of Radiation
      Oncology. In case of significantly elevated NRS-2002 (NRS >= 3), a guideline
      compliant, individual nutritional treatment was initiated by a specialized
      nutrition support team. The influence of the nutritional status and nutritional
      treatment on length of stay and complication rate was assessed. RESULTS: Of 840
      included patients, 344 patients (40.95%) were at risk for malnutrition.
      Malnutrition was a significant, independent risk factor for both prolonged
      hospital stay, represented by the deviation between the actual length of stay and
      the DRG-associated mean length of stay (dLOS at risk: 0.88 days, dLOS not at
      risk: -0.88 days, p = 0.0047), as well as for the occurrence of complications
      (OR: 1.758 CI: [1.286-2.402], p = 0.0006). In the group of 337 (40.12%)
      rehospitalized patients the nutritional management was able to assimilate the
      values of length of stay as well as the complication rates to standard values.
      CONCLUSIONS: The high risk for malnutrition and the negative consequences for
      patients and hospitals underline the urgent need for malnutrition screening on
      admission and treatment of malnutrition. A specialized, interdisciplinary
      nutrition support team positively influences patient outcome and should be
      established routinely in all oncological disciplines.

PMID- 30182248
TI  - Local land use associated with socio-economic development in six arctic regions.
AB  - The socioeconomic causes of land use change are complex. They are highly context
      dependent, but most often studied through case studies. Here, we use a quasi
      experimental paired block design to investigate whether better access to wage
      income leads to more visible land use around 28 settlements in six regions of the
      circumpolar Arctic. We mapped visible land use on high-resolution satellite
      images taken both close to the settlements, and in a more remote area of
      extensive land use, and payed special attention to tracks of off-road vehicles
      (ORV). Despite considerable differences among regions, there was an overall
      positive relationship between better access to wage income and land use. Reindeer
      herding was also associated with more visible use, in particular ORV tracks.
      These results suggest that access to wage income in the mixed subsistence-cash
      communities of the Arctic could lead to more local use related to harvesting and
      reindeer herding.

PMID- 30182249
TI  - Relationship of Racial Residential Segregation to Newly Diagnosed Cases of HIV
      among Black Heterosexuals in US Metropolitan Areas, 2008-2015.
AB  - Social science and public health literature has framed residential segregation as
      a potent structural determinant of the higher HIV burden among black
      heterosexuals, but empirical evidence has been limited. The purpose of this study
      is to test, for the first time, the association between racial segregation and
      newly diagnosed heterosexually acquired HIV cases among black adults and
      adolescents in 95 large US metropolitan statistical areas (MSAs) in 2008-2015. We
      operationalized racial segregation (the main exposure) using Massey and Denton's
      isolation index for black residents; the outcome was the rate of newly diagnosed
      HIV cases per 10,000 black adult heterosexuals. We tested the relationship of
      segregation to this outcome using multilevel multivariate models of longitudinal
      (2008-2015) MSA-level data, controlling for potential confounders and time. All
      covariates were lagged by 1 year and centered on baseline values. We
      preliminarily explored mediation of the focal relationship by inequalities in
      education, employment, and poverty rates. Segregation was positively associated
      with the outcome: a one standard deviation decrease in baseline isolation was
      associated with a 16.2% reduction in the rate of new HIV diagnoses; one standard
      deviation reduction in isolation over time was associated with 4.6% decrease in
      the outcome. Exploratory mediation analyses suggest that black/white
      socioeconomic inequality may mediate the relationship between segregation and
      HIV. Our study suggests that residential segregation may be a distal determinant
      of HIV among black heterosexuals. The findings further emphasize the need to
      address segregation as part of a comprehensive strategy to reduce racial
      inequities in HIV.

PMID- 30182250
TI  - Breast cancer patients with brain metastasis undergoing GKRS.
AB  - BACKGROUND: Breast cancer (BC) is the second most common cause of brain
      metastasis in the United States. Compared to whole brain radiation therapy
      (WBRT), treatment with gamma-knife radiosurgery (GKRS) offers a better chance at
      neurocognitive preservation. The goal of our retrospective study is to report the
      overall survival (OS) in patients receiving GKRS and to identify factors that
      improve survival outcomes. METHODS: The records of 80 patients with primary BC
      treated with GKRS at the Yale Comprehensive Cancer Center between 2000 and 2013
      were reviewed. OS was calculated from the date of first GKRS treatment. Other
      factors studied were age, Karnofsky performance status (KPS), tumor subtype,
      having WBRT and/or surgical resection pre- or post-GKRS, and number of brain
      metastases treated with GKRS. RESULTS: Median age was 56.2 years. OS from first
      GKRS was 13.1 months (95% CI 7.6-21.9). On univariate analysis, improved survival
      was associated with HER-2 subtype (p = 0.026), KPS score > 80 (p = 0.009), and
      good control of systemic disease at time of GKRS (p = 0.020). Multivariable
      analysis detected a significantly longer survival with HER-2 positivity (HR 0.22,
      95% CI 0.06-0.76, p = 0.017) and a strong trend in patients with craniotomy prior
      to GKRS (HR 0.13, 95% CI 0.01-1.11, p = 0.06). CONCLUSIONS: GKRS is a promising
      therapy for treating brain metastasis from BC, particularly in those with HER-2
      positivity and high-performance scores even in those patients with > 5 brain
      metastases. Furthermore, GKRS may also be a useful adjunct to surgical resection
      in such patients. High rates of neurological death remain from BC brain
      metastases; however, and need further investigation.

PMID- 30182251
TI  - Serotonin transporter gene (5-HTT) rs6354 polymorphism, job-related stress, and
      their interaction in burnout in healthcare workers in a Chinese hospital.
AB  - OBJECTIVE: Many studies have reported that long-term exposure to job-related
      stress can lead to burnout, which may be influenced by genetic and environmental
      factors. Burnout correlates with depression. This study investigated whether one
      tag polymorphism rs6354 in 5-HTT gene modulated the influence of job-related
      stress on burnout in the medical professionals in a Chinese Han population, which
      to our best knowledge has not been explored. METHODS: Seven hundred twelve
      subjects were recruited from a general hospital and measured for burnout symptoms
      using the Maslach Burnout Inventory (MBI), the stress using the House and Rizzo's
      Work Stress Scale, and the stressors using the Evers, Frese, and Cooper's Sources
      of Pressure Scale. The 5-HTT rs6354 polymorphism was genotyped in 376 subjects.
      RESULTS: The majority of correlations between the work stress score or the six
      stressor scores and three burnout subscores were significant (all p < 0.05).
      There was no significant main effect of the 5-HTT rs6354 genotype on burnout
      symptoms; however, there was a statistically significant interaction between 5
      HTT rs6354 and work stress on burnout (F = 5.08, df = 2, 369, p = 0.007). In the
      low stress group, G allele carriers had significantly higher burnout level than
      TT homozygote (F = 11.60, df = 1, 48, p < 0.001). On the contrary, in the high
      stress group, G allele carriers exhibited significantly lower burnout level
      compared to TT homozygote (F = 3.86, df = 1, 103, p = 0.025). CONCLUSIONS: Our
      findings suggest that the 5-HTT rs6354 polymorphism may modulate the influence of
      job-related stress on burnout by adjusting serotonin transporter function and
      neurotransmission, showing that individuals with TT genotype displayed a greater
      susceptibility to both the detrimental effects of higher stress and the
      beneficial effects of lower stress compared to those with G allele, which
      supports the differential-susceptibility hypothesis.

PMID- 30182253
TI  - Textural analysis on contrast-enhanced CT in pancreatic neuroendocrine neoplasms:
      association with WHO grade.
AB  - PURPOSE: Grades of pancreatic neuroendocrine neoplasms (PNENs) are associated
      with the choice of treatment strategies. Texture analysis has been used in tumor
      diagnosis and staging evaluation. In this study, we aim to evaluate the potential
      ability of texture parameters in differentiation of PNENs grades. MATERIALS AND
      METHODS: 37 patients with histologically proven PNENs and underwent pretreatment
      dynamic contrast-enhanced computed tomography examinations were retrospectively
      analyzed. Imaging features and texture features at contrast-enhanced images were
      evaluated. Receiver operating characteristic curves were used to determine the
      cut-off values and the sensitivity and specificity of prediction. RESULTS: There
      were significant differences in tumor margin, pancreatic duct dilatation, lymph
      nodes invasion, size, portal enhancement ratio (PER), arterial enhancement ratio
      (AER), mean grey-level intensity, kurtosis, entropy, and uniformity among G1, G2,
      and pancreatic neuroendocrine carcinoma (PNEC) G3 (p < 0.01). Similar results
      were found between pancreatic neuroendocrine tumors (PNETs) G1/G2 and PNEC G3.
      AER and PER showed the best sensitivity (0.86-0.94) and specificity (0.92-1.0)
      for differentiating PNEC G3 from PNETs G1/G2. Mean grey-level intensity, entropy,
      and uniformity also showed acceptable sensitivity (0.73-0.91) and specificity
      (0.85-1.0). Mean grey-level intensity was also showed acceptable sensitivity (91%
      to 100%) and specificity (82% to 91%) in differentiating PNET G1 from PNET G2.
      CONCLUSIONS: Our data indicated that texture parameters have potential in grading
      PNENs, in particular in differentiating PNEC G3 from PNETs G1/G2.

PMID- 30182252
TI  - A cognitive model-based approach to testing mechanistic explanations for
      neuropsychological decrements during tobacco abstinence.
AB  - RATIONALE: Cigarette smokers often experience cognitive decrements during
      abstinence from tobacco, and these decrements may have clinical relevance in the
      context of smoking cessation interventions. However, limitations of the
      behavioral summary statistics used to measure cognitive effects of abstinence,
      response times (RT) and accuracy rates, may restrict the field's ability to
      identify robust abstinence effects on task performance and test mechanistic
      hypotheses about the etiology of these cognitive changes. OBJECTIVES: The current
      study explored whether a measurement approach based on mathematical models of
      cognition, which make the cognitive mechanisms necessary to perform choice RT
      tasks explicit, would be able to address these limitations. METHODS: The linear
      ballistic accumulator model (LBA: Brown and Heathcote, Cogn Psychol 57(3):153
      178, 2008) was fit to an existing data set from a study that evaluated the impact
      of overnight abstinence on flanker task performance. RESULTS: The model-based
      analysis provided evidence that smokers' rates of mind wandering increased during
      abstinence, and was able to index this effect while controlling for participants'
      strategy changes that were related to the specific experimental paradigm used.
      CONCLUSION: Mind wandering is a putative explanation for cognitive withdrawal
      symptoms during smoking cessation and may be indexed using the LBA. More broadly,
      the use of formal model-based analyses in future research on this topic has the
      potential to allow for strong and specific tests of mechanistic explanations for
      these symptoms.

PMID- 30182254
TI  - Cystobasidium keelungensis sp. nov., a novel mycosporine producing carotenogenic
      yeast isolated from the sea surface microlayer in Taiwan.
AB  - Cystobasidium keelungensis SN2T (CBS 6949 = BCRC 920080), a new anamorphic
      basidiomycetous yeast species, is described in this paper. The strains belonging
      to this species were isolated from the sea surface microlayer and underlying
      water in Taiwan. These strains were identified by examining nucleotide sequences
      in the species-specific D1/D2 domains of the large subunit (LSU) ribosomal RNA
      (rRNA) and by evaluating their physiological characteristics. Phylogenetic
      analyses of D1/D2 sequences revealed that C. keelungensis was most closely
      related to the species C. slooffiae (LSU rRNA gene sequence divergence of 1.5%),
      and it belonged to the Erythrobasidium clade. No sexual reproduction was
      observed. This species differed from related species in carbon and nitrogen
      assimilation patterns and growth at 35  degrees C. Screening C. keelungensis for
      the presence of UV-absorbing compounds showed that mycosporine-glutaminol
      glucoside and mycosporine-glutamicol-glucoside (maximum absorption: 310 nm) were
      the major UV-absorbing compounds, which differ from the compounds present in some
      freshwater yeast strains reported in previous studies. After UV induction, SN2
      had a higher level of mycosporine production than other carotenogenic yeasts in
      this study.

PMID- 30182255
TI  - MLST and RAPD molecular analysis of Staphylococcus aureus subsp. anaerobius
      isolated from goats in Poland.
AB  - Staphylococcus aureus subsp. anaerobius is an etiological agent of Morel's
      disease in small ruminants. The infection results in superficial abscesses
      located near lymph nodes. In the study, molecular analysis based on multilocus
      sequence typing (MLST) of seven housekeeping genes (arcC, aroE, glp, gmk, pta,
      tpi, yqiL) and random amplified polymorphic DNA (RAPD) was carried out on 19 S.
      aureus subsp. anaerobius strains isolated from two different goat herds from
      Poland. All of the 19 S. aureus subsp. anaerobius strains were found to belong to
      single MLST and RAPD types which support the high clonality level of this agent.
      However, the results obtained show clearly that the S. aureus subsp. anaerobius
      clone found in goats in Poland is different from those previously described.
      However, it is identical to the ATCC 38844 strain isolated from sheep in Spain,
      which has not been so far genotyped using MLST.

PMID- 30182257
TI  - Severe parasitism by Versteria mustelae (Gmelin, 1790) in the critically
      endangered European mink Mustela lutreola (Linnaeus, 1761) in Spain.
AB  - The riparian European mink (Mustela lutreola), currently surviving in only three
      unconnected sites in Europe, is now listed as a critically endangered species in
      the IUCN Red List of Threatened Species. Habitat loss and degradation,
      anthropogenic mortality, interaction with the feral American mink (Neovison
      vison), and infectious diseases are among the main causes of its decline. In the
      Spanish Foral Community of Navarra, where the highest density of M. lutreola in
      its western population has been detected, different studies and conservation
      measures are ongoing, including health studies on European mink, and invasive
      American mink control. We report here a case of severe parasitism with
      progressive physiological exhaustion in an aged free-ranging European mink
      female, which was accidentally captured and subsequently died in a live-trap
      targeting American mink. Checking of the small intestine revealed the presence of
      17 entangled Versteria mustelae worms. To our knowledge, this is the first
      description of hyperinfestation by tapeworms in this species.

PMID- 30182256
TI  - [Early onset substance abuse disorders and addictive diseases in old age].
AB  - During the past 20 years substance-related and addictive disorders in old age
      have markedly increased and this increase is going to continue. It is quite
      common to make a distinction between early onset (EO) and late onset (LO) of
      these disorders. EO-addicts are in a more disadvantageous position due to
      constitutional and psychosocial burdens and the cumulating harmful medical,
      mental and social consequences of addiction place them at a further disadvantage
      during the course of the disorder. In old age they are at a disadvantage compared
      to others of the same age with LO addiction problems because of more and more
      severe chronic medical conditions, psychiatric comorbidity, less personal and
      social resources, dysfunctional coping style, and social problems. They present
      with lower treatment adherence and the treatment is difficult due to the
      combination of typical addictive behavior, psychiatric comorbidity, somatic
      diseases and in many cases also cognitive impairment. Treatment goals must be
      mostly individually defined and abstinence is rarely a realistic goal. Even the
      treatment has to be carried out mostly individually and often unconventionally.
      This article gives a review of the characteristic features of the course,
      presentation and adverse consequences of addictive disorders in EO addicts who
      have reached old age. The article covers alcohol, prescription drugs, illicit
      drugs and smoking as well as behavioral addictions.

PMID- 30182258
TI  - Oxidative stress and neuroinflammation should be both considered in the
      occurrence of fatigue and depression in multiple sclerosis.
AB  - Oxidative stress and neuroinflammation have a role in the pathogenesis of
      multiple sclerosis (MS) and in depression. Fatigue is the most disabling symptom
      in patients with MS and could also be a part of depressive symptomatology. In
      this study, we measured the serum levels of uric acid (UA) as a marker of
      oxidative stress and C-reactive protein (CRP) as an inflammatory marker, in 98
      patients with MS in relapse and remitting phase of illness and 35 healthy
      subjects. Degree of depressive symptomatology and fatigue were assessed with
      Beck's Depression Inventory (BDI) and Fatigue Severity Scale (FSS). Further, we
      examined the possible correlation of these biomarkers with symptoms of depression
      and fatigue. Relapse and remitting MS had a lower serum UA levels than controls
      (236.97 +/- 9.25 umol/L vs. 268.27 +/- 0.09 umol/L vs. 314.82 +/- 11.02 umol/L; p
      = 0.000), while sera levels of CRP were higher in relapse than remitting patients
      (4.46 +/- 0.40 mg/L vs. 1.01 +/- 0.38 mg/L; p = 0.000). Patients in relapse had
      higher BDI scores (15.68 +/- 16.62 vs. 8.36 +/- 7.10; p = 0.045). Decreased UA
      levels showed weak negative correlation with the presence of sadness and
      disturbed daily activities, higher CRP levels positively correlated with severe
      depression and the correlation between depression and fatigue was also observed
      (p < 0.05). It is possible that decreased UA levels lead to sadness, disturbed
      daily activities and severe disability. Every attack of CRP elevation in relapse
      could additionally precipitate the depression onset. The clinicians must pay
      special attention to early detection of fatigue because it could precede
      depression and improve further treatment.

PMID- 30182259
TI  - Autoimmune encephalitis and immune therapy: lessons from Argentina.
AB  - Autoimmune encephalitis (AE) is a common cause of noninfectious acute
      encephalitis. We aimed to provide the first review of immune therapy regimens
      used for patients with AE in Latin America, as well as the safety and efficacy
      associated with them, by reviewing the medical records of Argentine patients with
      AE treated between 2013 and 2018. Data included clinical symptoms, laboratory
      tests, electroencephalography, magnetic resonance imaging, cerebral spinal fluid,
      and neoplasm screenings. We examined ten AE patients who received first-line
      immunotherapy at a median of 2.5 months following symptom onset. Among these
      patients, five required second-line treatment: three received therapy at a median
      of 4 months (2-112) after symptom onset and were treated with rituximab, while
      two received therapy at a median of 4.5 (4-5) months after onset and received
      methylprednisolone for 6 months and initiated chronic treatment with
      azathioprine. By the last follow-up, their respective outcomes improved
      significantly. On the modified Rankin Scale, the median score decreased from 5 to
      1 (p <= 0.05). Only two of the ten patients in our series experienced relapses;
      both had been treated with a combination of methylprednisolone and IVIG. The
      regimen after recurrence included rituximab and corticoids plus azathioprine.
      Neither patient had experienced another relapse by their last follow-up. Our
      findings demonstrate the importance of early and aggressive immunosuppressive
      therapy to achieve a good clinical outcome and a fast recovery without relapses.

PMID- 30182261
TI  - The volatile nature of positive affect effects: opposite effects of positive
      affect and time on task on proactive control.
AB  - There is growing evidence suggesting that positive affect promotes cognitive
      flexibility at the cost of increased distractibility and decreased proactive
      control. Regarding the latter effect, some studies revealed inconsistent or even
      diverging findings casting doubt on the reliability of this observation.
      Recently, it has been shown that motivation can counteract positive affect
      effects. Here, the authors provide evidence for another factor that opposes
      positive affect effects, namely time on and experience with a task. To this end,
      the well proven AX-continuous performance task (AX-CPT) was used. Three groups of
      participants received three blocks of the AX-CPT with a positive affect
      manipulation (positive group) or neutral affect manipulation (neutral group) or
      alternating affect blocks (mixed group: pos-neut-pos). Results confirmed the
      positive affect effect associated with decreased proactive control in the
      positive and mixed group as compared to the neutral group. Most importantly, all
      groups showed an increase in proactive control with increasing time on task
      supporting our prediction that time on task is another factor opposing the
      positive affect effect. The results thus reveal the sensitivity of the positive
      affect effect to strategic influences developed with increasing experience with
      the given task. Implications for future research on the interplay of mild
      positive affect and cognitive control will be discussed.

PMID- 30182260
TI  - A novel nonsense autosomal dominant mutation in the GLRA1 gene causing
      hyperekplexia.
AB  - We present a family with two members affected by hyperekplexia and two unaffected
      members. All exons in the glycine receptor alpha 1 subunit gene (GLRA1) were
      sequenced in all four family members. Our index patient harbored a novel nonsense
      mutation (p.Trp314*; rs867618642) in the transmembrane domain three of the GLRA1
      and a novel missense variant in the NH2-terminal part (p.Val67Met; rs142888296).
      After development of tolerance for the effective treatment with clobazam a drug
      holiday led to a sustained restoration of the treatment response.

PMID- 30182262
TI  - Adsorption dynamics of hydrophobically modified polymers at an air-water
      interface.
AB  - Using surface-tension measurements, we study the brush-limited adsorption
      dynamics of a range of amphiphilic polymers, PAAH-[Formula: see text]-[Formula:
      see text] composed of a poly(acrylic acid) backbone, PAAH, grafted with a
      fraction [Formula: see text] of alkyl moieties, containing either n = 8 or n = 12
      carbon atoms, at pH conditions where the PAAH backbone is not charged. At short
      times, the surface tension decreases more sharply as the degree of grafting
      increases, while, at long times, the adsorption dynamics becomes logarithmic in
      time and is slower as the degree of grafting increases. This logarithmic behavior
      at long times indicates the building of a free-energy barrier which grows over
      time. To account for the observed surface tension evolution with the degree of
      grafting we propose a scenario, where the free-energy barrier results from both
      the deformation of the incoming polymer coils and the deformation of the adsorbed
      brush. Our model involves only two fitting parameters, the monomer size and the
      area needed for one molecule during adsorption and is in agreement with the
      experimental data. We obtain a reasonable value for the monomer size and find an
      area per adsorbed polymer chain of the order of 1 nm2, showing that the polymer
      chains are strongly stretched as they adsorb.

PMID- 30182263
TI  - Ventral hernia recurrence in women of childbearing age: a systematic review and
      meta-analysis.
AB  - BACKGROUND: There is no consensus agreement on the optimal management strategy
      for ventral hernia in women of childbearing age. The theoretical increased risk
      of ventral hernia recurrence can impact management strategies. We conducted a
      systematic review of the literature to report the ventral hernia recurrence rate
      in women of childbearing age who underwent hernia repair prior to their pregnancy
      and propose a management algorithm. METHODS: We systematically searched multiple
      databases including MEDLNE, PubMed, and the Cochrane Library sources from
      inception to August, 2017. Two reviewers independently identified 314 primary
      studies, assessed methodological quality, and extracted data. Quality of included
      studies was assessed by employing the Newcastle Ottawa quality assessment tool
      for cohort studies. A separate tool was utilized for assessing the methodological
      quality of case series. A meta-analysis of proportions was conducted of studies
      reporting incidence of recurrence using STATA, employing a random effects model,
      to calculate a pooled weighted incidence rate (with 95% confidence interval).
      Descriptive statistics were employed to report the findings of studies which did
      not report any ventral hernia recurrence. RESULTS: Five retrospective studies
      were included in our review, enrolling a total of 14,638 female participants.
      Upon stratifying patients according to pregnancy status after primary hernia
      repair, 13,494 were found to be in the non-pregnant cohort whereas 1,144 were
      included in the pregnant cohort. Overall, 9% (95% CI 8-9%) of the non-pregnant
      patients experienced a recurrence whereas 12% (95% CI 10-15%) of patients that
      became pregnant subsequent to a ventral hernia repair experienced a recurrence.
      No major adverse events were recorded throughout the course of pregnancy.
      CONCLUSIONS: Ventral hernias in women of childbearing age have a pooled
      recurrence rate of 12%. Pregnancy may be considered a risk factor for ventral
      hernia recurrence. Female patients of childbearing age with asymptomatic or
      minimally symptomatic ventral hernias that do not pose a significant strain on
      the patients' quality of life could be provided with the option of watchful
      waiting, with appropriate education of risks while discussing management.

PMID- 30182265
TI  - [Influence of aspirin on bleeding-related complications after hepatic surgery].

PMID- 30182264
TI  - Production of optically pure L(+)-lactic acid from waste plywood chips using an
      isolated thermotolerant Enterococcus faecalis SI at a pilot scale.
AB  - Utilization of renewable and low-cost lignocellulosic wastes has received major
      focus in industrial lactic acid production. The use of high solid loadings in
      biomass pretreatment potentially offers advantages over low solid loadings
      including higher lactic acid concentration with decreased production and capital
      costs. In this study, an isolated Enterococcus faecalis SI with optimal
      temperature 42  degrees C was used to produce optically pure L-lactic acid (>
      99%) from enzyme-saccharified hydrolysates of acid-impregnated steam explosion
      (AISE)-treated plywood chips. The L-lactic acid production increased by 10% at 5
      L scale compared to the similar fermentation scheme reported by Wee et al. The
      fermentation with a high solid loading of 20% and 35% (w/v) AISE-pretreated
      plywood chips had been successfully scaled up to process development unit scale
      (100 L) and pilot scale (9 m3), respectively. This is the first report of pilot
      scale lignocellulosic lactic acid fermentation by E. faecalis with high lactic
      acid titer (nearly 92 g L-1) and yield (0.97 kg kg-1). Therefore, large-scale L
      lactic acid production by E. faecalis SI shows the potential application for
      industries.

PMID- 30182266
TI  - [The German snowball effect : An increasing aftercare problem in bariatric
      treatment].
AB  - BACKGROUND: The surgical treatment of obesity in Germany is a rapidly developing
      field which is strictly controlled by national guidelines. OBJECTIVE: Depiction
      of the burden on obesity centers by the exponential increase in numbers of
      patients following bariatric treatment. METHODS: In a retrospective study the
      numbers of outpatients at this university obesity center (founded 2007) were
      descriptively analyzed. Outpatient visits were documented annually and divided
      into two groups: primary visit and follow-up visit. The frequency of bariatric
      operations as well as their acceptance/cost coverage by health insurances were
      evaluated. RESULTS: Overall 318 patients were seen in 2007: 156 primary and 162
      follow-up visits. The health insurance rejection rate for cost coverage was
      16.8%. There were 1691 outpatient visits in 2016 (2016 vs. 2007: +532%), of which
      487 (+312%) were primary and 1204 (+743%) follow-up visits. The health insurance
      rejection rate dropped to 1.8%, while the frequency of operations increased
      nearly tenfold. CONCLUSION: With the increasing acceptance of bariatric surgery,
      a relatively low number of specialized centers have to deal with an exponentially
      rising follow-up frequency. In consideration of the extent of the obesity
      epidemic an adequate follow-up constitutes a socioeconomic problem, which can
      only be solved in an interdisciplinary setting under structural integration.

PMID- 30182267
TI  - [Intrahepatic cholangiocarcinoma - current perspectives and treatment algorithm].
AB  - Cholangiocarcinoma (CCC) is the second most common primary malignancy of the
      liver and is typically diagnosed at advanced disease stages. Among curative
      treatment options for CCC, radical surgical resection with extrahepatic bile duct
      resection, hepatectomy, and en-bloc lymphadenectomy are considered the mainstay
      of curative therapy. The assessment of the functional liver reserve by dynamic
      liver function tests and the estimation of the remaining future liver volume
      (future liver remnant, FLR) are of paramount importance. The introduction of
      novel interventional and surgical techniques, such as portal vein embolization,
      associating liver partition, and portal vein ligation for staged hepatectomy
      (ALPPS), have enabled clinicians to achieve resectability even in patients
      previously deemed unresectable. Radiofrequency ablation (RFA) shows acceptable
      results in small intrahepatic cholangiocarcinoma (IHCC) in liver cirrhosis and
      should be evaluated if cirrhosis precludes surgical treatment. Transarterial
      chemoembolization (TACE) or transarterial radioembolization (TARE) alone or in
      combination with systemic therapy may be applied in cases of surgical
      irresectability. According to recent results of the British BILCAP trial,
      adjuvant therapy may be considered after surgical resection in curative intent.

PMID- 30182268
TI  - [Trochanteric and subtrochanteric fractures].
AB  - Proximal femoral fractures are one of the most common fractures, particularly in
      older people. The most common cause is a falling event due to dizziness and gait
      insecurity. In most cases prompt surgical treatment is necessary to achieve early
      mobilization and to reduce the risk of mortality. The aim is a stable
      osteosynthesis and patient-centered care. A great variety of implants are
      available for this purpose. Furthermore, perioperative management is important to
      prevent further problematic events, such as delirium, reoccurrence of falling
      events and to diagnose and adequately treat a pre-existing osteoporosis.

PMID- 30182269
TI  - The governance structure for data access in the DIRECT consortium: an innovative
      medicines initiative (IMI) project.
AB  - Biomedical research projects involving multiple partners from public and private
      sectors require coherent internal governance mechanisms to engender good working
      relationships. The DIRECT project is an example of such a venture, funded by the
      Innovative Medicines Initiative Joint Undertaking (IMI JU). This paper describes
      the data access policy that was developed within DIRECT to support data access
      and sharing, via the establishment of a 3-tiered Data Access Committee. The
      process was intended to allow quick access to data, whilst enabling strong
      oversight of how data were being accessed and by whom, and any subsequent
      analyses, to contribute to the overall objectives of the consortium.

PMID- 30182270
TI  - Observation of anterior chamber volume after cataract surgery with swept-source
      optical coherence tomography.
AB  - PURPOSE: To investigate the changes in the anterior chamber volume (ACV) with
      swept-source optical coherence tomography (SS-OCT) after cataract surgery and the
      factors that influence these ACV changes. METHODS: This was a prospective cohort
      study. Fifty-one patients who underwent cataract surgery were enrolled. Their
      ACV, anterior chamber depth, and angle widths were measured with SS-OCT before
      and 1 day, 1 week, and 1 month after surgery. The associations between the
      changes in ACV and posterior vitreous detachment (PVD) and axial length (AXL)
      were determined. RESULTS: Compared with the preoperative volume, ACV increased
      significantly at all three time points after surgery (all p < 0.001). ACV was
      greater at 1 week after surgery than at 1 day after surgery (p < 0.001). Both AXL
      and the presence of PVD were significantly associated with the change in ACV at 1
      day after surgery (p = 0.005). However, neither PVD nor AXL affected the change
      in ACV between 1 day and 1 week after surgery. CONCLUSIONS: ACV stabilized in the
      first week after cataract surgery. The absorption of irrigation fluid and
      balanced salt solution in the vitreous cavity contributed to the change in ACV 1
      week after surgery. Eyes with longer AXL and PVD tended to show less change in
      ACV at 1 day after surgery.

PMID- 30182271
TI  - The characteristic of intraocular pressure dynamic change in patients with
      glaucomatocyclitic crisis.
AB  - PURPOSE: To investigate the characteristic of intraocular pressure (IOP) dynamic
      change from episode to intermittent period in patients with Posner-Schlossman
      syndrome (PSS). PATIENTS AND METHODS: Seventeen cases of typical PSS were
      collected in this study. Both their random IOP in episodes/intermittent period
      and 24-h IOP in intermittent period were measured. The mean IOP as well as the
      peak and the valley value of 24-h IOP were calculated. Those data were
      statistically analyzed. RESULTS: The IOP in affected eye in episodes is higher
      than that of the contralateral eye statistically; while in intermittent period
      the mean IOP (p = 0.001), the peak (p = 0.029) and the valley (p = 0.004) value
      of 24-h IOP in affected eye are statistically different with that of the
      contralateral eye. All of these parameters of the affected eye in intermittent
      period are lower than that of the contralateral eye obviously. CONCLUSION: The
      dynamic observations of IOP in episodes and intermittent period confirmed the IOP
      crossover phenomenon inpatients with typical PSS and this observation may be
      important in the differential diagnosis of PSS.

PMID- 30182272
TI  - Global dynamics of a mutualism-competition model with one resource and multiple
      consumers.
AB  - Recent simulation modeling has shown that species can coevolve toward clusters of
      coexisting consumers exploiting the same limiting resource or resources, with
      nearly identical ratios of coefficients related to growth and mortality. This
      paper provides a mathematical basis for such as situation; a full analysis of the
      global dynamics of a new model for such a class of n-dimensional consumer
      resource system, in which a set of consumers with identical growth to mortality
      ratios compete for the same resource and in which each consumer is mutualistic
      with the resource. First, we study the system of one resource and two consumers.
      By theoretical analysis, we demonstrate the expected result that competitive
      exclusion of one of the consumers can occur when the growth to mortality ratios
      differ. However, when these ratios are identical, the outcomes are complex.
      Either equilibrium coexistence or mutual extinction can occur, depending on
      initial conditions. When there is coexistence, interaction outcomes between the
      consumers can transition between effective mutualism, parasitism, competition,
      amensalism and neutralism. We generalize to the global dynamics of a system of
      one resource and multiple consumers. Changes in one factor, either a parameter or
      initial density, can determine whether all of the consumers either coexist or go
      to extinction together. New results are presented showing that multiple competing
      consumers can coexist on a single resource when they have coevolved toward
      identical growth to mortality ratios. This coexistence can occur because of
      feedbacks created by all of the consumers providing a mutualistic service to the
      resource. This is biologically relevant to the persistence of pollination
      mutualisms.

PMID- 30182273
TI  - Keeping your eye on the target: eye-hand coordination in a repetitive Fitts'
      task.
AB  - In a cyclical Fitts' task, hand movements transition from continuous to discrete
      movements when the Index of Difficulty (ID) increases. Moreover, at high ID
      (small target), the eyes saccade to and subsequently fixate the targets at every
      movement, while at low ID (large target) intermittent monitoring is used. By
      hypothesis, the (periodic) gaze shifts are abandoned for movement times shorter
      than about 0.350 s due to systemic constraints (i.e., a refractory period and
      intrinsic latency). If so, the transition in eye and hand movements is
      independent. To investigate these issues, the present study examined the effects
      of changing ID via the targets' width or distance as well as hysteresis in eye
      hand coordination. To this aim, 14 participants performed a cyclical Fitts' task
      while their hand and eye movements were recorded simultaneously. The results show
      that the transition in eye-hand synchronization (at 2.87 bit; 0.25 s) and in hand
      dynamics (at 4.85 bit; 0.81 s) neither co-occurred nor correlated. Some small
      width vs. distance dissociations and hysteresis effects were found, but they
      disappeared when eye-hand synchronization was viewed as a function of movement
      time rather than ID. This confirms that a minimal between-saccade time is the
      limiting factor in eye-hand synchronization. Additionally, the timing between the
      start of the hand movement and the saccade appeared to be relatively constant (at
      0.15 s) and independent of movement time, implying a constant delay that should
      be implemented in a dynamical model of eye-hand coordination.

PMID- 30182274
TI  - Quality of life is related to the functional connectivity of the default mode
      network at rest.
AB  - Quality of life is an important issue concerning people all over the world and
      affecting patients in the mental health field. When considering the potential
      neural links between quality of life and the brain, a brain network that comes
      into mind is the default mode network (DMN). Its architecture and function has
      been investigated in relation to various research fields including social and
      emotional cognition, meditation and neuropsychiatric disorders as well as
      happiness. In this cross-sectional study we investigated the relationship between
      various quality of life domains (physiological, psychological, social and
      environmental) and the functional connectivity of the default mode network at
      rest in a sample of 42 healthy working female managers. The results indicate that
      there is a significant association between the social quality of life domain and
      the functional connectivity of the default mode network. Post-hoc analysis
      revealed that high social quality of life scores were associated with right-left
      lateral parietal hypoconnectivity. By adopting a wide ranging perspective, our
      study approaches to fundamental research about quality of life but so far only
      applied on a female subgroup. As far as we know, it is the first to analyze the
      neuronal correlates of quality of life in the brain and therefore sets an initial
      step in its investigation.

PMID- 30182275
TI  - Age-related and seasonal changes in covalently bound ceramide content in forearm
      stratum corneum of Japanese subjects: determination of molecular species of
      ceramides.
AB  - The stratum corneum (SC) consists of corneocytes surrounded by a neutral lipid
      enriched intercellular matrix. Ceramides represent approximately 50% of
      intercellular lipids, and play important roles in retaining epidermal water. The
      SC also contains covalently bound ceramides, which are thought to play a crucial
      role in the formation of lamellar structures, and are involved in maintaining
      skin barrier function. A previous report showed that levels of free ceramides in
      human SC changed with the seasons and age, although whether the content of
      different species of covalently bound ceramides also underwent such temporal
      changes was unclear. Here, SC samples were taken from 99 healthy individuals of
      different ages (24-64 years) and during different seasons. The content of
      different molecular species of covalently bound ceramides in the samples was
      quantified using HPLC-MS/MS. The levels of total covalently bound ceramides
      (Total-Cers) significantly decreased approximately 50% in autumn and winter,
      compared with that of spring and summer. The levels of covalently bound ceramides
      containing saturated fatty acids (SFA-Cers) in the spring and summer were
      approximately 2.3-fold higher than that seen in autumn and winter, whereas the
      level of covalently bound ceramides containing unsaturated fatty acids (USFA
      Cers) in spring and summer were approximately 1.6-fold higher than that in autumn
      and winter. Furthermore, the ratio between SFA-Cers and USFA-Cers was
      significantly lower in spring and summer than in autumn and winter. The levels of
      SFA-Cers, but not USFA-Cers, were significantly lower in individuals >= 50 years
      old compared to those who are 30- and 40-years old in the spring. Our study
      showed for the first time that, similar to free ceramides, the level of
      covalently bound ceramides changed with the seasons. However, age-related changes
      in covalently bound ceramide content were limited in that only the amount of SFA
      Cers in the spring was lower in older individuals.

PMID- 30182276
TI  - The BET bromodomain inhibitor i-BET151 impairs ovarian cancer metastasis and
      improves antitumor immunity.
AB  - Ovarian cancer (OC) is a common malignant tumor with a high probability of
      metastasis. Thus, it is urgently necessary to develop new drugs that inhibit
      tumor metastasis. Bromodomain and extraterminal (BET) inhibitors targeting
      bromodomain-containing proteins are currently recognized as novel anticancer
      agents. Herein, we explored the effects of i-BET151, a BET bromodomain inhibitor,
      on OC metastasis and on antitumor immunity. Our experiments showed that i-BET151
      decreased the viability and induced apoptosis, senescence, and cell cycle arrest
      of cancer cells. In addition, phosphorylated-Stat3 (Tyr705) amounts OC cell
      invasion and migration, and expression of matrix metalloproteinases (MMP-9 and
      MMP-2) decreased. Moreover, tumor metastasis in the abdomen of the OC model was
      inhibited by i-BET151. Notably, i-BET151-promoted immunogenic cell death (ICD)
      was confirmed in vivo; it was demonstrated with ICD markers. Furthermore,
      treatment with i-BET151 promoted infiltration by CD8+ T cells as well as the
      death of immunogenic tumor cells. In summary, tumor metastasis may be suppressed
      by i-BET151 via the Stat3 pathway; this approach could be used as a strategy for
      the treatment of OC.

PMID- 30182277
TI  - Pediatric Inflammatory Bowel Disease in India: Time to Prepare for Challenges and
      Opportunities.

PMID- 30182278
TI  - Predicting Complicated Parapneumonic Effusion in Community Acquired Pneumonia:
      Hospital Based Case-Control Study.
AB  - OBJECTIVE: To identify predictors of complicated parapneumonic effusion
      (CPE)/empyema in patients of community acquired pneumonia (CAP) by using clinical
      and simple laboratory variables like hemoglobin (Hb), serum C-reactive protein
      (CRP), serum albumin (SA) levels and total leukocyte counts (TLC). METHODS: This
      prospective case-control study was conducted after institutional ethical
      approval. Subjects between ages of 2-59 mo with World Health Organization (WHO)
      defined CAP with written, informed parental consent were included. Cases had CAP
      with CPE/empyema diagnosed by pleurocentesis. Controls had severe CAP without
      significant pleural collection on chest X-ray (CXR). Patients with congenital and
      chronic diseases/infections and possible immune deficiency were excluded.
      Variables with univariate association with case-control status were considered as
      potential predictors. Final prediction model was developed by Forward Stepwise
      Logistic Regression (FSLR). Adjusted odd's ratios (Adj OR) were smoothened into
      nearest whole numbers to develop KGMU-CPE score. RESULTS: From 2016 to 17, 30
      cases (66.6% males, age 38.7 + 14.9 mo) and 118 controls (78% males, age 17.8 +
      16.9 mo) were included. In FSLR, predictors of CPE/empyema were ibuprofen intake
      (adj OR 6.8; 95%CI: 1.07-43.6), infective focus elsewhere (adj OR 28.2; 95%CI:
      1.4-563.1), hypoalbuminemia <3.1 g/dL (adj OR 6.9; 95%CI: 1.22-39.3), serum CRP
      >20 mg/dL (adj OR 59; 95%CI: 1.86-1874.7), Hb <10 g/dL (adj OR 21.1; 95%CI: 2.8
      158.1) and TLC >10,000 (adj OR 37; 95%CI: 5.7-239.8) and these six variables
      formed KGMU-CPE Score with a minimum score of 0 and maximum of 25. KGMU-CPE score
      area under the ROC curve was 0.97 and cut- off 15.55 had sensitivity of 80% and
      specificity of 94% for predicting CPE/empyema. CONCLUSIONS: Using simple clinical
      and laboratory parameters it is possible to predict CAP with CPE/empyema. Use of
      ibuprofen is to be avoided in CAP as it associated with CPE. KGMU-CPE score had
      good diagnostic accuracy and needs external validation.

PMID- 30182279
TI  - Triage Nurse-Ordered Diagnostic Studies - An Evolving Strategy to Reduce
      Emergency Department Length of Stay?

PMID- 30182280
TI  - In vitro demethoxycarbonylation of various chlorophyll analogs by a BciC enzyme.
AB  - Unique light-harvesting antennas in the green sulfur bacterium Chlorobaculum
      tepidum, called chlorosomes, consist of self-aggregates of bacteriochlorophyll
      (BChl) c. In the biosynthesis of BChl c, BciC demethoxycarbonylase removes the
      C132-methoxycarbonyl group to facilitate the self-aggregation of BChl c. We
      previously reported the in vitro BciC-enzymatic reactions and discussed the
      function of this enzyme in the biosynthesis of BChl c. This study aims to examine
      the substrate specificity of BciC in detail using several semi-synthetic
      (bacterio)chlorophyll derivatives. The results indicate that the substrate
      specificity of BciC is measurably affected by structural changes on the A/B rings
      including the bacteriochlorin pi-systems. Moreover, BciC showed its activity on a
      Zn-chelated chlorophyll derivative. On the contrary, BciC recognized structural
      modifications on the D/E rings, including porphyrin pigments, which resulted in
      the significant decrease in the enzymatic activity. The utilization of BciC
      provides mild conditions that may be useful for the in vitro preparation of
      various chemically (un)stable chlorophyllous pigments.

PMID- 30182281
TI  - International Symposium: Trailblazing in Cancer Immunotherapy, October 29-31,
      2017, Pamplona, Spain.

PMID- 30182282
TI  - HIV, HCV and HBV: A Review of Parallels and Differences.
AB  - Elimination of the three blood-borne viruses-human immunodeficiency virus (HIV),
      hepatitis B (HBV) and hepatitis C (HCV)-as public health issues may be plausible
      in the near future. Spectacular advances have been made with the introduction of
      highly effective antiviral agents into clinical practice, and prevention
      strategies are available for all three infections. Effective disease control,
      laid out by WHO global strategies, is currently feasible for all three viruses.
      However, for worldwide elimination of these viruses, effective vaccines are
      required that are currently only available for HBV. In this review differences
      and parallels among HIV, HCV and HBV will be discussed with a focus on virologic
      and therapeutic issues, and prospects for the future of HBV will be presented.

PMID- 30182284
TI  - The efficacy and safety of calcitonin gene-related peptide monoclonal antibody
      for episodic migraine: a meta-analysis.
AB  - OBJECTIVE: This meta-analysis was performed to evaluate the efficacy and safety
      of monoclonal antibodies against calcitonin gene-related peptide (CGRP) for
      episodic migraine prevention. METHODS: MEDLINE, EMBASE, Web of Science, and the
      Cochrane Library were searched from inception to April 2018. Studies considered
      to be eligible were randomized controlled trials about efficacy and safety of
      calcitonin gene-related peptide monoclonal antibody for episodic migraine
      prevention. RESULTS: Eight randomized controlled trials involving 2292 patients
      were included. The outcomes of this meta-analysis presented that CGRP monoclonal
      antibodies for preventive treatment of episodic migraine significantly reduced
      the monthly migraine days from baseline [weighted mean difference (WMD) = - 1.52;
      95%CI, - 1.92 to - 1.11; Z = 7.40; P < 0.001] and monthly acute migraine-specific
      medication consumption from baseline [WMD = - 1.45; 95%CI, - 2.17 to - 0.72; Z =
      3.93; P < 0.001], as compared with placebo group. CGRP monoclonal antibodies for
      preventive treatment of episodic migraine significantly increased the >= 50%
      reduction from baseline in migraine days per month [RR = 1.54; 95%CI, 1.38
      to1.71; Z = 7.88; P < 0.001]. The adverse events were similar between the CGRP
      monoclonal antibody group and placebo group (P = 0.998). The outcomes of subgroup
      analysis showed that erenumab, galcanezumab, and fremanezumab significantly
      reduced the monthly migraine days from baseline and increased the >= 50%
      reduction from baseline in migraine days per month. Both erenumab and
      fremanezumab significantly reduced from baseline. CONCLUSIONS: Based on the
      results of this meta-analysis, CGRP monoclonal antibodies significantly reduced
      the monthly migraine days and acute migraine-specific medication. CGRP monoclonal
      antibodies were effective and safe for preventive treatment of episodic migraine.

PMID- 30182283
TI  - Carrier Transport Properties of MoS2 Asymmetric Gas Sensor Under Charge Transfer
      Based Barrier Modulation.
AB  - Over the past few years, two-dimensional materials have gained immense attention
      for next-generation electric sensing devices because of their unique properties.
      Here, we report the carrier transport properties of MoS2 Schottky diodes under
      ambient as well as gas exposure conditions. MoS2 field-effect transistors (FETs)
      were fabricated using Pt and Al electrodes. The work function of Pt is higher
      than that of MoS2, while that of Al is lower than that of MoS2. The MoS2 device
      with Al contacts showed much higher current than that with Pt contacts because of
      its lower Schottky barrier height (SBH). The electrical characteristics and gas
      responses of the MoS2 Schottky diodes with Al and Pt contacts were measured
      electrically and were simulated by density functional theory calculations. The
      theoretically calculated SBH of the diode (under gas absorption) showed that NOx
      molecules had strong interaction with the diode and induced a negative charge
      transfer. However, an opposite trend was observed in the case of NH3 molecules.
      We also investigated the effect of metal contacts on the gas sensing performance
      of MoS2 FETs both experimentally and theoretically.

PMID- 30182285
TI  - Intracellular Ca2+ mobilization pathway via bradykinin B1 receptor activation in
      rat trigeminal ganglion neurons.
AB  - Bradykinin (BK) and its receptors, B1 and B2, in trigeminal ganglion (TG) neurons
      are involved in the regulation of pain. Recent studies have revealed that B1
      receptors are expressed in neonatal rat TG neurons; however, the intracellular
      signaling pathway following B1 receptor activation remains to be elucidated. To
      investigate the mechanism by which B1 receptor activation leads to intracellular
      Ca2+ mobilization, we measured the intracellular free Ca2+ concentration
      ([Ca2+]i) in primary-cultured TG neurons. The application of Lys-[Des-Arg9]BK (B1
      receptor agonist) increased the [Ca2+]i in these TG neurons even in the absence
      of extracellular Ca2+. Pretreatment with inhibitors of ryanodine receptors or
      sarco/endoplasmic reticulum Ca2+-ATPase suppressed the increase in Lys-[Des
      Arg9]BK-induced [Ca2+]i. The Lys-[Des-Arg9]BK-induced [Ca2+]i increase was
      unaffected by phospholipase-C inhibitor. B1 receptor activation-induced [Ca2+]i
      increase was suppressed by phosphodiesterase inhibitor and enhanced by adenylyl
      cyclase inhibitor. These results suggest that B1 receptor activation suppresses
      intracellular cAMP production via adenylyl cyclase inhibition and mobilizes
      intracellular Ca2+ via ryanodine receptors that access intracellular Ca2+ stores.

PMID- 30182287
TI  - Cross-education does not improve early and late-phase rehabilitation outcomes
      after ACL reconstruction: a randomized controlled clinical trial.
AB  - PURPOSE: Limited evidence suggests that cross-education affords clinical benefits
      in the initial 8 weeks after anterior cruciate ligament (ACL) reconstruction, but
      it is unknown if such cross-education effects are reproducible and still present
      in later phases of rehabilitation. We examined whether cross-education, as an
      adjuvant to standard therapy, would accelerate the rehabilitation up to 26 weeks
      after ACL reconstruction by attenuating quadriceps weakness. METHODS: ACL
      reconstructed patients were randomized into experimental (n = 22) and control
      groups (n = 21). Both groups received standard care after ACL reconstruction. In
      addition, the experimental group strength trained the quadriceps of the non
      operated leg during weeks 1-12 after surgery (i.e., cross-education). Self
      reported knee function was assessed with the Hughston Clinic Knee score as the
      primary outcome. Secondary outcomes were maximal quadriceps and hamstring
      strength and single leg hop distance. All outcomes were measured 29 +/- 23 days
      prior to surgery, as a reference, and at 5-week, 12-week, and 26-week post
      surgery. RESULTS: Both groups scored 12% worse on self-reported knee function 5
      week post-surgery (95% CI 7-17) and showed 15% improvement 26-week post-surgery
      (95% CI - 20 to - 10). No cross-education effect was found. Interestingly, males
      scored 8-10% worse than females at each time point post-surgery. None of 33
      secondary outcomes showed a cross-education effect. At 26-week post-surgery, both
      legs improved maximal quadriceps (5-14%) and hamstring strength (7-18%), and the
      non-injured leg improved 2% in hop distance. The ACL recovery was not affected by
      limb dominance and age. CONCLUSION: 26 weeks of standard care improved self
      reported knee function and maximal leg strength relative to pre-surgery and
      adding cross-education did not further accelerate ACL recovery. LEVEL OF
      EVIDENCE: I. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION: This randomized
      controlled clinical trial is registered at the Dutch trial register (
      http://www.trialregister.nl ) under NTR4395.

PMID- 30182286
TI  - Effects of beta-alanine and sodium bicarbonate supplementation on the estimated
      energy system contribution during high-intensity intermittent exercise.
AB  - The effects of beta-alanine (BA) and sodium bicarbonate (SB) on energy metabolism
      during work-matched high-intensity exercise and cycling time-trial performance
      were examined in 71 male cyclists. They were randomised to receive BA + placebo
      (BA, n = 18), placebo + SB (SB, n = 17), BA + SB (BASB, n = 19), or placebo +
      placebo (PLA, n = 18). BA was supplemented for 28 days (6.4 g day-1) and SB (0.3
      g kg-1) ingested 60 min before exercise on the post-supplementation trial.
      Dextrose and calcium carbonate were placebos for BA and SB, respectively. Before
      (PRE) and after (POST) supplementation, participants performed a high-intensity
      intermittent cycling test (HICT-110%) consisting of four 60-s bouts at 110% of
      their maximal power output (60-s rest between bouts). The estimated contribution
      of the energy systems was calculated for each bout in 39 of the participants (BA:
      n = 9; SB: n = 10; BASB: n = 10, PLA: n = 10). Ten minutes after HICT-110%,
      cycling performance was determined in a 30-kJ time-trial test in all
      participants. Both groups receiving SB increased estimated glycolytic
      contribution in the overall HICT-110%, which approached significance (SB: + 23%,
      p = 0.068 vs. PRE; BASB: + 18%, p = 0.059 vs. PRE). No effects of supplementation
      were observed for the estimated oxidative and ATP-PCr systems. Time to complete
      30 kJ was not significantly changed by any of the treatments, although a trend
      toward significance was shown in the BASB group (p = 0.06). We conclude that SB,
      but not BA, increases the estimated glycolytic contribution to high-intensity
      intermittent exercise when total work done is controlled and that BA and SB,
      either alone or in combination, do not improve short-duration cycling time-trial
      performance.

PMID- 30182288
TI  - [Eduard Reich's "Hygiene of Culture"-A retrospective on the occasion of the 100th
      anniversary of his death].
AB  - In contrary to the developing significance of the bacteriology and the chemical
      and physical noxious influences of the environment for Eduard Reich the main
      cause of decision between health and illness are the functions of the "soul".
      Components of this as important for the normal life are virtue (i. e. solidarity,
      performance of duty, self-knowledge), good sense to realize correlations,
      morality, charity and mercifulness (social behaviour). The goal of the hygiene
      therefore is to promote the good and to hinder the evil, as well for a complete
      person or only one of his organs as for the whole society. The final aim is not
      only the improvement of the common efficiency for any economic or military
      purposes but also the preservation of health of the soul.In accordance to these
      duties and aims Reich divides the hygiene into four parts.The "Moral Hygiene"
      regulates the activities directed by the brain supported by education, training
      and religion.The "Social Hygiene" cares for the wealth of the whole population.
      In Reich's time, it applied in particular to the labour, the basis for it are
      moral, hygiene and economy, but migration too played a great role.The "Dietetic
      Hygiene"-the oldest task of the preservation of health-cares for the human
      somatic necessities and the use of the organs. Prerequisite for this are bodily
      exercise and moderation, hence moral and physical training. The aim is not only
      preserving of the health but also gaining high age in health.The "Policed
      Hygiene" (Sanitary Police) has to care for the observance of reassurances for the
      public health. It must be done with charity and kindness and has to paralyse a
      heartless economy as poverty is the worst enemy of health. The duties of the
      sanitary police in the various districts should be fulfilled by boards of health,
      of education and of public safety. Each of these boards consists of a legislative
      and an executive part.Reich's concept of the hygiene as result of the application
      of moral and charity as well in the lifetime of each individual as of the whole
      society justifies the already forgotten terminus "Hygiene of Culture".

PMID- 30182289
TI  - Current status of functional imaging in neuroblastoma, pheochromocytoma, and
      paraganglioma disease.
AB  - Diagnostic imaging plays an important role in the detection of paraganglioma
      (PGL), pheochromocytoma (PCC), and neuroblastoma (NB). Anatomic imaging, for
      example CT or MRI, offers high sensitivity in these neuroendocrine tumors (NET)
      but only moderate specificity, often associated with difficulties in clearly
      distinguishing between NET and non-NET. Functional imaging, as in the use of
      different radioisotopes, is indispensable in oncological imaging. The
      introduction of PET and PET/CT, respectively, led to a dramatic improvement in
      both malignant and non-malignant PGL, PCC, and NB, assessing the exact tumor
      extent. This review gives an overview of functional and anatomical imaging in
      PGL, PCC, and NB.

PMID- 30182291
TI  - Primary adenocarcinoma of the appendix in a child: A case report.
AB  - BACKGROUND: Primary adenocarcinoma of the appendix is a rare disease in clinical
      practice. Moreover, primary adenocarcinoma of the appendix in the pediatric age
      group is even rarer with very little cases being published. Here, we report a
      case of primary adenocarcinoma of the appendix with local invasion into adjacent
      organs in a child who was initially diagnosed as having an acute appendicitis.
      CASE PRESENTATION: A 13-year-old girl presented with abdominal pain of 3-month
      duration. Imaging study showed a mass including the fecalith that occupied her
      pelvic and right lower abdominal cavity. Drainage of the abscess and appendectomy
      were performed by the preoperative diagnosis of an acute appendicitis with an
      appendiceal mass. Postoperative histopathological examinations revealed the
      appendiceal adenocarcinoma. She then received the whole mass resection, ileocecal
      resection with lymph node dissection. The masses were tightly adherent with
      infiltration into the sigmoid colon, uterus, and right ovary. These organs were
      all dissected, and subsequent sigmoid colostomy was performed. We preserved the
      left ovary for her fertility. The pathological findings demonstrated negative
      margins and no lymph node invasions, and final pathological stage was
      pT4(SI)N0M0, stage II. After the operation, she received the chemotherapy with 6
      cycles of 5-fluorouracil (5-FU), leucovorin (LV), and oxaliplatin (mFOLFOX6) and
      subsequent 6 cycles of simplified LV and 5-FU (sLV5FU2). The patient is doing
      well till today on follow-up without progression of the disease 5 years after the
      operation. CONCLUSION: Primary adenocarcinoma of the appendix is exceedingly rare
      in children. In this report, we described one of the youngest primary
      adenocarcinomas of an appendix case ever reported. When encountering atypical
      cases of the appendicitis, we should consider the possibility of primary
      adenocarcinoma of the appendix as it has an extremely poor prognosis and is
      usually diagnosed in advanced stages.

PMID- 30182292
TI  - Sclerostin: a biomarker for chronic kidney disease and vascular disease with
      added or independent value?

PMID- 30182290
TI  - Clinical presentation, treatment and outcome of Takayasu's arteritis in southern
      Chinese: a multicenter retrospective study.
AB  - To study the clinical presentation, treatment and outcome of southern Chinese
      patients with Takayasu's arteritis (TA). This is a retrospective chart review
      study of 78 patients managed in 14 public hospitals in Hong Kong between the
      years 2000 and 2010. Patients were identified from the hospital registry using
      the ICD-10 diagnostic code of the disease. The classification of TA was based on
      the American College of Rheumatology (ACR) or modified Ichikawa's criteria.
      Demographic data, clinical presentation, angiographic findings, pattern of
      vascular involvement (Numano's classification), treatment and outcome of these
      patients were presented. 78 patients were studied (82% women, age at presentation
      34.2 +/- 14 years). The estimated point prevalence of TA was 11/million
      population. The commonest initial manifestations were hypertension (62%) and
      vascular ischemic symptoms (38%). Systemic symptoms occurred in nine (12%)
      patients only. The proportion of patients fulfilling the angiographic subtypes of
      the Numano's classification was: types I (13%), IIa (4%), IIb (12%), III (12%),
      IV (20%) and V (39%), respectively. Thirty-two patients (41%) were treated with
      high-dose glucocorticoids (GCs) and 22 patients (28%) received additional non-GC
      immunosuppressive drugs. Vascular complications occurred in 26 (33%) patients and
      revascularization surgery was performed in 23(29%) patients. Three (4%) patients
      died of vascular complication at a median of 8 years after disease onset. TA is
      rare in southern Chinese patients of Hong Kong. Most patients present with
      ischemic symptoms during the stenotic phase of the disease. Although mortality is
      low, a significant proportion of patients developed vascular stenosis that
      required surgical interventions. More awareness of TA as a differential diagnosis
      of non-specific systemic symptoms with elevated inflammatory markers in younger
      patients is needed for earlier diagnosis.

PMID- 30182293
TI  - Thiamine status in end-stage chronic kidney disease patients: a single-center
      study.
AB  - BACKGROUND: Reportedly, thiamine deficiency, resulting from malnutrition and long
      term diuretic therapy, is observed in patients with chronic kidney disease (CKD).
      The risk of thiamine deficiency might be enhanced, especially in end-stage CKD
      patients. Here, we assessed thiamine status in incident dialysis patients.
      METHODS: This study was a single-center cross-sectional study which included 288
      consecutive patients initiated into dialysis between April 2013 and March 2017 at
      our hospital. Thiamine status was evaluated by high-performance liquid
      chromatography of whole blood samples. We evaluated the association between blood
      thiamine concentration and other clinical parameters. RESULTS: Of the 288
      patients, 21 patients receiving thiamine supplementation at the time of dialysis
      initiation and 26 patients without blood thiamine measurements were excluded. In
      30 patients (12.4%), blood thiamine concentration was lower than the lower limit
      of normal (21.3 ng/mL; dotted line). Blood thiamine concentration correlated with
      age, body mass index, and Barthel index (BI) score (p = 0.008, 0.012 and 0.009,
      respectively). Stepwise multivariate regression analysis indicated that BI scores
      were independent risk factors for thiamine deficiency (beta coefficients = 0.169,
      p = 0.013). CONCLUSIONS: The proportion of end-stage CKD patients with low blood
      thiamine concentration is high. Low physical function (low BI score) is an
      independent risk factor of thiamine deficiency. Clinicians should be aware of
      thiamine deficiency in end-stage CKD patients, especially those with low physical
      function.

PMID- 30182294
TI  - Both insulin resistance and metabolic syndrome accelerate the progression of
      chronic kidney disease among Chinese adults: results from a 3-year follow-up
      study.
AB  - BACKGROUND: Metabolic syndrome (MetS) has been found to be associated with an
      increased risk for chronic kidney disease (CKD). However, the relationship
      between insulin resistance (IR), which is believed to play a central role in the
      pathogenesis of MetS, and CKD is still unclear in Chinese adults and needs
      further investigation. METHODS: This 3-year follow-up study included 3237 middle
      aged and elderly Chinese without CKD at baseline. Estimated glomerular filtration
      rate (eGFR) 60-90 mL/min/1.73 m2 was defined as the mildly reduced eGFR; CKD was
      defined as eGFR < 60 mL/min/1.73 m2. MetS was defined based on the China
      guideline for type 2 diabetes. IR was measured by the homeostatic model
      assessment of IR (HOMA-IR). Incidences of mildly reduced eGFR and CKD from normal
      eGFR were calculated. The roles of MetS and IR in predicting the progression of
      CKD were estimated using multiple logistic regression models. RESULTS: The
      incidences of CKD and mildly reduced eGFR for the entire cohort were 20.08 and
      33.28 per 1000 person-years, respectively. A large proportion [13.1% (182/1394)]
      of patients with mildly reduced eGFR progressed to CKD in 3 years. After
      accounting for age, gender, five components of MetS and HOMA-IR in multiple
      logistic regression model, only IR presented increased OR (1.119, 95% CI 1.052
      1.189, p < 0.001) for CKD. When we included MetS instead of its five components
      in model, both MetS (OR 1.420, 95% CI 1.020-1.977, p = 0.038) and HOMA-IR (OR
      1.118, 95% CI 1.055-1.186, p < 0.001) showed increased risk for CKD progression.
      CONCLUSIONS: Both IR and MetS accelerate the progression of CKD among Chinese
      adults. Single metabolic abnormality did not have enough potency to induce the
      occurrence of CKD in 3 years.

PMID- 30182295
TI  - Application of SRT plus MR recession in supra-maximal esotropia from chronic
      sixth nerve palsy.
AB  - BACKGROUND: To investigate prognostic factors in patients with augmented superior
      rectus transposition (SRT) for sixth nerve palsy. METHODS: Thirteen patients who
      were diagnosed with sixth nerve palsy and underwent augmented SRT between January
      2015 and February 2017 in EENT Hospital of Fudan University were reviewed
      retrospectively. Data including age, sex, etiology of the abducens nerve palsy,
      degree of pre- and postoperative deviation in the primary position, pre- and
      postoperative abduction deficit, any induced vertical or torsional deviations,
      reoperations, and other complications was collected. Patients with
      undercorrection of SRT surgeries received additional inferior rectus
      transposition (IRT) surgery. RESULTS: Mean esodeviation in primary position
      improved from 81.92? to 30.54? (p < 0.001) with a 1.54-unit improvement in
      abduction (p = 0.001). Six patients achieved alignment defined as esodeviation in
      primary position within 10? of orthotropia and seven patients were undercorrected
      after the first SRT surgery. Multivariable linear regression analysis showed that
      among factors (disease duration, preoperative esodeviation, preoperative
      abduction deficit), only the degree of preoperative abduction deficit (beta = -
      13.68) was the prognostic factor for success of SRT surgery. After IRT
      procedures, the mean esodeviation in primary position improved from 40? to 8? (p
      < 0.01). CONCLUSION: The degree of preoperative abduction deficit is the
      prognostic factor for augmented SRT for sixth nerve palsy. Patients with worse
      abduction deficit have a greater likelihood of needing a secondary operation, and
      IRT could be a good choice for reoperation after SRT.

PMID- 30182296
TI  - Impedimetric immunosensor for dengue diagnosis using graphite screen-printed
      electrodes coated with poly(4-aminophenylacetic acid).
AB  - Dengue is an infectious viral disease transmitted by the Aedes aegypti mosquito,
      the control of which is complex. In addition, the clinical diagnosis is difficult
      to perform since it resembles other febrile infections; thus, the development of
      more effective methods to detect dengue virus (DV) has drawn increasing
      attention. The present study aimed to develop an impedimetric immunosensor for
      dengue diagnosis using a screen-printed electrode (SPE) functionalized with
      polymer films derived from 4-aminophenylacetic acid (4-APA). Data obtained from
      scanning electron microscopy (SEM) showed the deposition of a uniformly
      distributed material over the electrode surface. The immunosensor was based on
      the specific interaction between dengue antigen, NS1 protein, and anti-NS1
      antibodies, IgG and IgM. In a characterization study using cyclic voltammetry
      (CV), the polymer film showed two oxidation peaks at +0.17 and + 0.35 V in 0.50 M
      sulfuric acid solution, indicating its adsorption and electroactivity at the SPE
      surface. Electrochemical impedance spectroscopy (EIS) measurements showed a
      higher charge transfer resistance (Rct) to the polymer film-modified SPE as
      compared with the bare SPE, corroborating a previous study. The best rNS1
      concentration for immobilization was 1.00 ng/mL, and the immunoreaction time
      between the antigen (Ag) and the antibody (Ab) was 20 min. Dilutions of positive
      and negative clinical serum samples were evaluated by EIE, from which it was
      possible to elucidate, for the positive serum, that the more diluted the serum
      the greater the Rct. Negative serum also showed an analytical signal, probably
      due to the presence of non-specific antibodies; however, the generated signal
      presented values closer to the rNS1 signal, indicating good selectivity of the
      proposed platform. The experiments were repeated using bare SPE to verify the
      importance of the polymer film in biosensor construction. No significant
      difference was observed between these results. Graphical abstract Proposed
      schematic for the genosensor development.

PMID- 30182297
TI  - 3D-MRI versus 3D-CT in the evaluation of osseous anatomy in femoroacetabular
      impingement using Dixon 3D FLASH sequence.
AB  - OBJECTIVE: To determine if hip 3D-MR imaging can be used to accurately
      demonstrate femoral and acetabular morphology in the evaluation of patients with
      femoroacetabular impingement. MATERIALS AND METHODS: We performed a retrospective
      review at our institution of 17 consecutive patients (19 hips) with suspected
      femoroacetabular impingement who had both 3D-CT and 3D-MRI performed of the same
      hip. Two fellowship-trained musculoskeletal radiologists reviewed the imaging for
      the presence and location of cam deformity, anterior-inferior iliac spine
      variant, lateral center-edge angle, and neck-shaft angle. Findings on 3D-CT were
      considered the reference standard. The amount of radiation that was spared
      following introduction of 3D-MRI was also assessed. RESULTS: All 17 patients
      suspected of FAI had evidence for cam deformity on 3D-CT. There was 100%
      agreement for diagnosis (19 out of 19) and location (19 out of 19) of cam
      deformity when comparing 3D-MRI with 3D-CT. There were 3 type I and 16 type II
      anterior-inferior iliac spine variants on 3D-CT imaging with 89.5% (17 out of 19)
      agreement for the anterior-inferior iliac spine characterization between 3D-MRI
      and 3D-CT. There was 64.7% agreement when comparing the neck-shaft angle (11 out
      of 17) and LCEA (11 out of 17) measurements. The use of 3D-MRI spared each
      patient an average radiation effective dose of 3.09 mSV for a total reduction of
      479 mSV over a 4-year period. CONCLUSION: 3D-MR imaging can be used to accurately
      diagnose and quantify the typical osseous pathological condition in
      femoroacetabular impingement and has the potential to eliminate the need for 3D
      CT imaging and its associated radiation exposure, and the cost for this
      predominantly young group of patients.

PMID- 30182300
TI  - Thymocyte self-renewal and oncogenic risk in immunodeficient mouse models:
      relevance for human gene therapy clinical trials targeting haematopoietic stem
      cell populations?
AB  - Emerging evidence indicates that thymocyte self-renewal induced by progenitor
      deprivation carries an oncogenic risk that is modulated by intra-thymic
      competition from differentiation-committed cells. Here we discuss formative
      studies demonstrating that, in mice, early thymocytes acquire self-renewing
      potential when thymic progenitor supply is sub-physiological and the importance
      of cellular competition with this at-risk cell population to prevent lymphoid
      malignancy. We also consider the possibility that increased thymic residency
      time, established under conditions of limited cellular competition, may have
      contributed to oncogenesis observed in early SCID-X1 trials when combined with
      insertional activation of proto-oncogenes such as LMO2.

PMID- 30182298
TI  - The effect of auxin and strigolactone on ATP/ADP isopentenyltransferase
      expression and the regulation of apical dominance in peach.
AB  - KEY MESSAGE: We confirmed the roles of auxin, CK, and strigolactones in apical
      dominance in peach and established a model of plant hormonal control of apical
      dominance in peach. Auxin, cytokinin, and strigolactone play important roles in
      apical dominance. In this study, we analyzed the effect of auxin and
      strigolactone on the expression of ATP/ADP isopentenyltransferase (IPT) genes
      (key cytokinin biosynthesis genes) and the regulation of apical dominance in
      peach. After decapitation, the expression levels of PpIPT1, PpIPT3, and PpIPT5a
      in nodal stems sharply increased. This observation is consistent with the changes
      in tZ-type and iP-type cytokinin levels in nodal stems and axillary buds observed
      after treatment; these changes are required to promote the outgrowth of axillary
      buds in peach. These results suggest that ATP/ADP PpIPT genes in nodal stems are
      key genes for cytokinin biosynthesis, as they promote the outgrowth of axillary
      buds. We also found that auxin and strigolactone inhibited the outgrowth of
      axillary buds. After decapitation, IAA treatment inhibited the expression of
      ATP/ADP PpIPTs in nodal stems to impede the increase in cytokinin levels. By
      contrast, after GR24 (GR24 strigolactone) treatment, the expression of ATP/ADP
      IPT genes and cytokinin levels still increased markedly, but the rate of increase
      in gene expression was markedly lower than that observed after decapitation in
      the absence of IAA (indole-3-acetic acid) treatment. In addition, GR24 inhibited
      basipetal auxin transport at the nodes (by limiting the expression of PpPIN1a in
      nodal stems), thereby inhibiting ATP/ADP PpIPT expression in nodal stems.
      Therefore, strigolactone inhibits the outgrowth of axillary buds in peach only
      when terminal buds are present.

PMID- 30182299
TI  - Factor structure of the Q-LES-Q short form in an enrolled mental health clinic
      population.
AB  - PURPOSE: The Quality of Life, Enjoyment, and Satisfaction Questionnaire-Short
      Form (Q-LES-Q-SF) is a recovery-oriented, self-report measure with an uncertain
      underlying factor structure, variously reported in the literature to consist of
      either one or two domains. We examined the possible factor structures of the
      English version in an enrolled mental health population who were not necessarily
      actively engaged in care. METHODS: As part of an implementation trial in the U.S.
      Department of Veterans Affairs mental health clinics, we administered the Q-LES-Q
      SF and Veterans RAND 12-Item Health Survey (VR-12) over the phone to 576 patients
      across nine medical centers. We used a split-sample approach and conducted an
      exploratory factor analysis (EFA) and multi-trait analysis (MTA). Comparison with
      VR-12 assessed construct validity. RESULTS: Based on 568 surveys after excluding
      the work satisfaction item due to high unemployment rate, the EFA indicated a
      unidimensional structure. The MTA showed a single factor: ten items loaded on one
      strong psychosocial factor (alpha = 0.87). Only three items loaded on a physical
      factor (alpha = 0.63). Item discriminant validity was strong at 92.3%.
      Correlations with the VR-12 were consistent with the existence of two factors.
      CONCLUSIONS: The English version of the Q-LES-Q-SF is a valid, reliable self
      report instrument for assessing quality of life. Its factor structure can be best
      described as one strong psychosocial factor. Differences in underlying factor
      structure across studies may be due to limitations in using EFA on Likert scales,
      language, culture, locus of participant recruitment, disease burden, and mode of
      administration.

PMID- 30182302
TI  - Digital elevation model (DEM) coupled with geographic information system (GIS):
      an approach towards erosion modeling of Gumara watershed, Ethiopia.
AB  - This study describes efforts to identify erosion-prone areas in the Gumara
      watershed using digital elevation model (DEM) data coupled with geographic
      information system (GIS). The software used to perform the overall analysis were
      the ESRI ArcGIS v10.3.1 with the ESRI Spatial Analyst and ArcHydro extension. All
      thematic layers (viz., slope, stream power index, drainage frequency, drainage
      density, drainage texture, relative relief, plan curvature, profile curvature)
      were integrated and analyzed in a GIS. A numeric evaluation scale from 1 to 4 was
      selected for ranking the subclasses of themes. The higher value, 4, represents
      higher impacts, while the lower value, 1, represents the lowest impact. About
      21.71% of the total watershed area is under severe erosion zone. While 32.13%,
      23.75%, and 22.42% of the total watershed area falls in moderate, low, and very
      low erosion zones respectively. In this paper, the numerical classification
      scheme presented constitutes an integrated approach that shows how to leverage
      basic watershed information to demarcate erosion prospective zones and measures
      at various scales for the purposes of watershed management.

PMID- 30182301
TI  - How much does community-based targeting of the ultra-poor in the health sector
      cost? Novel evidence from Burkina Faso.
AB  - BACKGROUND: Targeting efforts aimed at increasing access to care for the poorest
      by reducing to a minimum or completely eliminating payments at point of use are
      increasingly being adopted across low and middle income countries, within the
      framework of Universal Health Coverage policies. No evidence, however, is
      available on the real cost of designing and implementing these efforts. Our study
      aimed to fill this gap in knowledge through the systematic assessment of both the
      financial and economic costs associated with designing and implementing a pro
      poor community-based targeting intervention across eight districts in rural
      Burkina Faso. METHODS: We conducted a partial retrospective economic evaluation
      (i.e. estimating costs, but not benefits) associated with the abovementioned
      targeting intervention. We adopted a health system perspective, including all
      costs incurred by the government and its development partners as well as costs
      incurred by the community when working as volunteers on behalf of government
      structures. To trace both financial and economic costs, we combined Activity
      Based Costing with Resource Consumption Accounting. To this purpose, we consulted
      and extracted information from all relevant design/implementation documents and
      conducted additional key informant structured interviews to assess the resource
      consumption that was not valued in the documents. RESULTS: For the entire
      community-based targeting intervention, we estimated a financial cost of USD
      587,510 and an economic cost of USD 1,213,447. The difference was driven
      primarily by the value of the time contributed by the community. Communities
      carried the main economic burden. With a total of 102,609 ultra-poor identified,
      the financial cost and the economic cost per ultra-poor person were respectively
      USD 5,73 and USD 11,83. CONCLUSION: The study is first of its kind to accurately
      trace the financial and economic costs of a community-based targeting
      intervention aiming to identify the ultra-poor. The financial costs amounted to
      USD 5,73 and the economic costs to USD 11,83 per ultra-poor person identified.
      The financial costs of almost USD 6 represents 21% of the per capita government
      expenditure on health.

PMID- 30182303
TI  - Repeatability of central corneal thickness measurements of donor corneas in
      preservation chamber using Fourier-domain anterior segment optical coherence
      tomography.
AB  - To evaluate the repeatability of central corneal thickness (CCT) measurements in
      donor corneas using optical coherence tomography (OCT, RTVue-Optovue, Inc.,
      Fremont, CA). Consecutive corneas were measured by a single observer using the
      RTVue. All corneas were preserved in the Transend chamber and Life4  degrees C
      media (Numedis, Inc., Isanti, MN/USA) and stored at 4  degrees C. The
      repeatability was evaluated using a pooled within-subject standard deviation
      (SD), coefficient of variation (CoV), and intraclass correlation coefficient
      (ICC). To investigate inter-observer repeatability, a second observer
      independently measured the CCT for each image scan. CCT was measured in 32 eyes
      from 18 donors. Measurements were independently repeated by a second observer.
      The corneas had a mean CCT of 490.99 MUm +/- 65.95 (381-642) as measured by
      Observer 1. For observer 1, the SD value for the CCT was 2.94 MUm, the CoV value
      was 0.597%, and the ICC value was 0.998 (95% CI 0.996, 0.999). For observer 2,
      the SD value was 5.91 MUm, the CoV value was 1.21%, and the ICC value was 0.992
      (95% CI 0.985, 0.996). The Kappa statistic 21.88% with a p value < 0.001. The
      Bland-Altman plot shows that the average CCT measurements between the two
      observers were within 20 MUm of each other. The CCT measurements of donor corneas
      in the preservation chamber using Fourier domain OCT is highly repeatable.

PMID- 30182304
TI  - Multiplex PCR using YeaD and 16S rRNA gene to identify major pathogens in
      vibriosis of Litopenaeus vannamei.
AB  - The Vibrio species causing major diseases in Litopenaeus vannamei are Vibrio
      harveyi, Vibrio alginolyticus, and Vibrio parahaemolyticus. For multiplex PCR
      primers, YeaD was used to detect the three Vibrio species. Bioinformatic analysis
      such as MultiPLX and primer-BLAST was used to design stable and species-specific
      multiplex PCR primers. Multiplex PCR results showed clear band patterns with
      bands at 185 bp for V. alginolyticus, 396 bp for V. harveyi, 805 bp for V.
      arahaemolyticus, and 596 bp for common Vibrio species. The minimum concentration
      of DNA was measured by PCR; the value for V. alginolyticus was 0.1 ng, that of V.
      harveyi was 0.03 ng, and that of V. parahaemolyticus was 0.003 ng. Taken
      together, YeaD showed stability and specificity in identifying Vibrio species.
      Our multiplex PCR amplification method is an effective and inexpensive tool for
      identifying Vibrio species.

PMID- 30182305
TI  - BRF2 as a promising indicator for radical lymph-node dissection surgery in
      patients with cN0 squamous cell carcinoma of the middle thoracic esophagus.
AB  - PURPOSE: Radical lymph-node dissection surgery in patients with cN0 middle
      thoracic esophageal squamous cell carcinoma (ESCC) remains controversial. We
      sought a novel biomarker that could be used for decision-making in relation to
      radical lymph-node dissection. METHODS: One hundred and nineteen patients with
      cN0 middle thoracic ESCC undergoing three-field lymph-node dissection (3FLND) or
      two-field lymph-node dissection (Ivor Lewis) esophagectomy were reviewed. A
      survival analysis, and Chi-square and parametric tests were performed. RESULTS: A
      Cox regression analysis revealed that the expression of BRF2 was an independent
      prognostic factor for overall survival (P = 0.014) and progression-free survival
      (P = 0.014). The survival of patients who underwent 3FLND was better than that of
      patients who underwent Ivor Lewis esophagectomy in the BRF2 overexpression group
      (P = 0.002), but not in the BRF2 nonoverexpression group (P = 0.386). The risk of
      lymph-node recurrence and the number of recurrent lymph nodes in patients with
      the overexpression of BRF2 were increased in the Ivor Lewis group in comparison
      to the 3FLND group (P = 0.01 and P < 0.001). The risk of cervical and superior
      mediastinal lymph-node recurrence was positively correlated with the
      overexpression of BRF2 (P = 0.027). Furthermore, in the Ivor Lewis group, a
      significant correlation was found between the risk of lymph-node recurrence or
      the number of recurrent lymph nodes and the expression of BRF2 (P = 0.002 and P =
      0.004), but not in the 3FLND group (P = 0.193 and P = 0.694). CONCLUSIONS: 3FLND
      generated better survival outcomes and reduced the rate of lymph-node recurrence
      in comparison to Ivor Lewis in patients with the overexpression of BRF2. BRF2 can
      be used as an indicator for radical lymph-node dissection surgery in cN0 ESCC
      patients.

PMID- 30182306
TI  - Prevalence of and risk factors for thyroid carcinoma in patients with familial
      adenomatous polyposis: results of a multicenter study in Japan and a systematic
      review.
AB  - PURPOSE: To investigate the recent Japanese prevalence of thyroid cancer and its
      characteristics in familial adenomatous polyposis (FAP) patients, through the
      development of surveillance programs. METHODS: The subjects of this study were
      282 (93.1%) FAP patients for whom information on thyroid cancer was available,
      from among 303 patients registered in "the Retrospective Cohort Study of Familial
      Adenomatous Polyposis in Japan" database. We evaluated the prevalence and risk
      factors for thyroid cancer and integrated and/or compared our findings with those
      of previous reports, using a systematic review, including a meta-analysis.
      RESULTS: Thyroid cancer was diagnosed in 16 women (11.4%) and 2 men (1.4%), at 17
      41 years and 39-57 years of age, respectively. The prevalence of thyroid cancer
      was 6.4%, with a female-to-male ratio of 8:1, which is comparable to reports from
      other countries. A young age of < 33 years at the FAP diagnosis and female gender
      were identified as independent risk factors for thyroid cancer. CONCLUSIONS: FAP
      associated thyroid cancer predominantly affects young women, both in Japan and
      other countries. Since FAP is generally diagnosed when patients are in their 20 s
      or older, regular screening for thyroid cancer is recommended for all FAP
      patients, but especially women, from their early 20 s.

PMID- 30182307
TI  - Dimensions of the spinous process and interspinous space: a morphometric study.
AB  - PURPOSE: To measure the morphological dimensions of the spinous process (SP) and
      interspinous space, and provide a basis for the development of interspinous
      devices for the Korean or East Asian populations. METHODS: We retrospectively
      analyzed the anatomical parameters of 120 patients. The parameters included
      height, length, and width of SP, interspinous distance (supine, standing, and
      dynamic), cortical thickness of SP, and spino-laminar (S-L) angle. Correlations
      between measurements, age, and gender were investigated. RESULTS: The largest
      height, length, and cortical thickness and S-L angle were noted at L3. The
      largest width was observed at S1. The interspinous distance decreased
      significantly from L2-3 to L5-S1 and was significantly larger in the supine than
      in standing posture for L5-S1. Cortical thickness was gradually tapered from the
      anterior to the posterior position. The S-L angle at L2 and L3 was similar and
      significantly decreased from L3 to S1. An increased trend in width with aging and
      a decreased trend in distance (supine) were noted. A significant increase in
      height, length, and distance in males compared with females was also observed.
      CONCLUSIONS: The interspinous space is wider at the anterior, and the cortex is
      thicker anteriorly. Accordingly, it appears that the optimized implant position
      lies in the interspinous space anteriorly. The varying interspinous space with
      different postures and gradually narrowing with age suggest the need for caution
      when sizing the device. Gender differences also need to be considered when
      designing implantable devices.

PMID- 30182308
TI  - The effect of simple imputations based on four variants of PCA methods on the
      quantiles of annual rainfall data.
AB  - Hydrology-related studies often require complete datasets. However, missing data
      is an unavoidable reality. In this regard, the imputed data could fulfill the
      same role as the observed ones, while they are uncertain and just estimated. The
      aim of this study is to compare the performance of four simple imputation
      variants derived from the principal component analysis (PCA) for imputing annual
      total rainfall series obtained from stations located in northeast Algeria. On the
      other hand, the study focuses on the effects on quantiles of annual rainfall data
      due to imputations by the former methods. The four variants are probabilistic
      PCA, expectation maximization PCA, regularized PCA, and singular value
      decomposition PCA. Annual rainfall data from 30 stations for the period ranging
      from 1935 to 2004 (69 years) are used to generate and impute gaps for four
      different percentages of missing values (PMV), namely, 10, 20, 30, and 40%. Based
      on some well-known statistical indices, the results show that the regularized PCA
      and expectation maximization PCA variants perform better than the other
      imputation methods considered in this study and result in very good to acceptable
      predicted quantiles, such as the following: correlation coefficient is equal to
      0.97 with 10% of percentage of missing values and 0.66 with 40%; the relative
      error between observed and predicted quantiles is equal to 4.74% with 10% of
      percentage of missing values and 3.82% with 40%.

PMID- 30182309
TI  - Concise Commentary: Quercetin Flavonoid of the Month or IBD Therapy?

PMID- 30182310
TI  - Altered Metabolic Profile of Triglyceride-Rich Lipoproteins in Gut-Lymph of
      Rodent Models of Sepsis and Gut Ischemia-Reperfusion Injury.
AB  - BACKGROUND: Triglyceride-rich lipoproteins are important in dietary lipid
      absorption and subsequent energy distribution in the body. Their importance in
      the gut-lymph may have been overlooked in sepsis, the most common cause of
      critical illness, and in gut ischemia-reperfusion injury, a common feature of
      many critical illnesses. AIMS: We aimed to undertake an exploratory study of
      triglyceride-rich lipoprotein fractions in gut-lymph using untargeted metabolic
      profiling to identify altered metabolites in sepsis or gut ischemia-reperfusion.
      METHODS: The gut-lymph was collected from rodent sham, sepsis, and gut ischemia
      reperfusion models. The triglyceride-rich lipoprotein-enriched fractions isolated
      from the gut-lymph were subjected to a dual metabolomics analysis approach: non
      polar metabolite analysis by ultra-high performance liquid chromatography-mass
      spectrometry and polar metabolite analysis by gas chromatography-mass
      spectrometry. RESULTS: The metabolite analysis of gut-lymph triglyceride-rich
      lipoprotein fractions revealed a significant increase (FDR-adjusted P value <
      0.05) in myo-inositol in the sepsis group and monoacylglycerols [(18:1) and
      (18:2)] in gut ischemia-reperfusion. There were no significantly increased
      specific metabolites in the lipoprotein-enriched fractions of both sepsis and gut
      ischemia-reperfusion. In contrast, there was a widespread decrease in multiple
      lipid species in sepsis (35 out of 190; adjusted P < 0.05), but not in the gut
      ischemia-reperfusion. CONCLUSIONS: Increased levels of myo-inositol and
      monoacylglycerols, and decreased multiple lipid species in the gut-lymph
      triglyceride-rich lipoprotein fraction could be candidates for new biomarkers
      and/or involved in the progression of sepsis and gut ischemia-reperfusion
      pathobiology.

PMID- 30182311
TI  - Co-Administration of Progesterone and Melatonin Attenuates Ischemia-Induced
      Hippocampal Damage in Rats.
AB  - Stroke is the second leading reason for death worldwide and is one of the
      fundamental causes of long-term disabilities. The aim of this investigation was
      to assess the impact of combined administration progesterone (PROG) and melatonin
      (MEL) on stroke complications. Male Wistar rats (9-10 weeks) weighing 250-300 g
      were used as a part of this examination. They were randomly separated into eight
      groups (nine rats for every group). Common carotid arteries on the two sides
      clamped (BCCAO model) with non-traumatic clips for 20 min. At that point, the
      rats were treated with 8 mg/kg PROG, 10 mg/kg MEL, and vehicles (sesamoid and
      normal saline). Morris water maze testing was performed following 2 weeks. At
      that point, the rats were euthanized, and histological examination was directed.
      The outcome demonstrated that utilization of PROG and MEL in treatment groups
      essentially increases the quantity of pyramidal cells and enhances spatial memory
      compared to non-treatment groups (p < 0.05). Moreover, the neuroleptic factor
      gene expression and protein concentration were significantly enhanced in the
      treated groups (p < 0.05). As indicated by the outcomes, co-administration of
      PROG and MEL can enhance learning and memory by surviving the pyramidal neurons
      and diminishing neural death by means of increasing neuroleptic factors in the
      hippocampal CA1 zone.

PMID- 30182312
TI  - Determinants of pollution and the role of the military sector: evidence from a
      maximum likelihood approach with two structural breaks in the USA.
AB  - We investigate the role of military expenditure on emission in USA during the
      period 1960-2015. To achieve the objectives of this study, two measures of
      military expenditure are utilised, while several timeseries models are
      constructed with the gross domestic product (GDP) per capita, population, energy
      consumption per capita, non-renewable energy consumption per capita, renewable
      energy consumption per capita, urbanisation, trade openness and financial
      development serving as additional determinants of air pollution. We also use
      ecological indicator as an alternative measure of pollution. Moreover, different
      timeseries methods are utilised including a likelihood-based approach with two
      structural breaks. The output of this research concluded that all the variables
      are cointegrated. It is found that military expenditure has mixed impact on CO2
      emissions. Real GDP per capita, energy consumption per capita, non-renewable
      energy consumption per capita, population and urbanisation increase CO2 emissions
      per capita in the long-run, while renewable energy consumption, financial
      development and trade openness reduce it. There is also evidence for the mixed
      role of military expenditure, when ecological footprint is utilised as the
      environmental degradation index. From the output of this research, few policy
      recommendations are offered for the examined country.

PMID- 30182313
TI  - Adsorption of cadmium, nickel and lead ions: equilibrium, kinetic and selectivity
      studies on modified clinoptilolites from the USA and RSA.
AB  - The performance of modified clinoptilolites (zeolites) from two different sources
      (South Africa and the USA) for the adsorption of Ni2+, Cd2+ and Pb2+ from
      synthetic industrial effluent contaminated with metal concentration levels at 50,
      150 and 500 ppm was evaluated. The selectivity of the clinoptilolite for the
      adsorption of Ni2+, Cd2+ and Pb2+ was investigated with mixed feed solutions
      containing all three ions in equal concentrations and single-component
      concentrations containing only one of the ions. The homoionic forms of the
      clinoptilolite were made of Na+, K+ and Ca2+. Batch experiments were then
      conducted to measure the uptake of metals by the zeolites. The zeolites were
      characterised using SEM, XRD and BET. The South African clinoptilolite showed a
      higher surface area and pore volume (17.52m2/g and 0.047cm3/g respectively) than
      the USA zeolite (12.26m2/g and 0.028cm3/g respectively) for the Na+ homoionic
      form. According to the equilibrium studies, the selectivity sequence was found to
      be Pb2+ > Cd2+ > Ni2+, with good fits being obtained using Langmuir and
      Freundlich adsorption isotherms for low metal concentrations. Examples of
      equilibrium adsorption capacities for RSA and USA clinoptilolite modified with
      Na+ for Pb were 26.94 mg/g and 27.06 mg/g when RSA-Na+ and USA-Na+ were used
      respectively. The adsorption was found to depend on the homoionic form of the
      zeolite and to a lesser extent the source of the zeolite. The selectivity of a
      particular zeolite for a particular heavy metal can be altered by the homoionic
      form of the zeolite. Overall, the adsorption capacity of the USA clinoptilolite
      was higher than the adsorption capacity of the SA clinoptilolite, revealing the
      potential of clinoptilolite in metal-polluted industrial effluent treatment.

PMID- 30182314
TI  - Tracing sediment sources in a mountainous forest catchment under road
      construction in northern Iran: comparison of Bayesian and frequentist approaches.
AB  - Development and land use change lead to accelerated soil erosion as a serious
      environmental problem in river catchments in Iran. Reliable information about the
      sources of sediment in catchments is therefore necessary to design effective
      control strategies. This study used a composite sediment source tracing procedure
      to determine the importance of forest road cuttings as a sediment source in a
      mountainous catchment located in northern Iran. A fallout radionuclide (137Cs)
      and 12 geochemical tracers (Ca, Cu, Fe, K, Mg, Mn, Na, Ni, OC, Pb, Sr and TN)
      were used to determine the relative contributions of three sediment source types
      (hillslopes, road cuttings and channel banks) to both suspended and bed sediment
      samples. Two mixing models based on different mathematical concepts were used to
      apportion the sediment sources: the mixture sampling importance resampling
      Bayesian model which incorporates the mass-balance matrix and a distribution
      model using normal and summed probability of normal distributions. The results of
      both mixing models indicated that sub-soil erosion from road cuttings and channel
      banks dominated the sources of river bed and suspended sediment samples,
      respectively. These results therefore highlight that conservation that works in
      the study area to remedy the sediment problem should initially focus on
      stabilisation and rehabilitation of road cuttings and channel banks. This
      successful application of a composite (radionuclide and geochemical) tracing
      technique for discriminating source end members characterised by different
      erosion processes underscores the importance of sub-soil erosion in this case
      study.

PMID- 30182315
TI  - Influence of earthworms on the nitrogen transfer of sewage sludge in the
      vermifilter process.
AB  - A 6-year laboratory study was conducted to explore the performance of the
      vermifilter (VF) on reducing sewage sludge. Sewage sludge was found to be reduced
      significantly in the VF and exhibited a better performance of sludge reduction as
      compared with the conventional biofilter (BF), which could be traced through the
      nitrogen-rich organic matter. The nitrogen stable isotope technology was applied
      to study the matter flow of sewage sludge in the VF process and the influence of
      earthworms Eisenia fetida on sewage sludge reduction. Results showed that (1) the
      protein material could be consumed more than the polysaccharide and lipid
      materials, respectively, in the VF; (2) the presence of earthworms could enhance
      the consumption capacity of the VF on the protein-rich material of the sewage
      sludge; (3) earthworms played a leading role on the nitrogen lifting of the
      sewage sludge, leading to the performance difference of the effluent sludge or
      biofilm sludge between the VF and BF; (4) in the VF, nitrogen-isotope
      accumulation in either biofilms or earthworms happened more significantly in the
      lower layer than in the upper one, while nitrogen transfer of sewage sludge
      happened more significantly in the upper layer than in the lower one; (5)
      earthworms improved the feeding environment of organisms (microorganisms in
      biofilms, moth fly larvae, Limacidaes, and Lymnaeidaes); (6) biofilms,
      Limacidaes, and moth fly larvae performed better than leeches, Lymnaeidaes, and
      moth fly adults at nitrogen transfer of sewage sludge.

PMID- 30182316
TI  - Nitrate leaching from open-field and greenhouse vegetable systems in China: a
      meta-analysis.
AB  - The potential for nitrate leaching in Chinese vegetable systems is substantial
      because of high inputs of nitrogen (N) fertilizer and water. To quantify the
      nitrate leaching and identify the key controlling factors in Chinese vegetable
      systems, we conducted a meta-analysis that included 221 data sets from 18 field
      studies. The results revealed that nitrate leaching over the entire crop growing
      season in Chinese vegetable systems was very high and averaged 79.1 kg N ha-1 and
      primarily resulted from extremely high N fertilizer inputs (in average 423 kg N
      ha-1). Nitrate leaching was, on the average, 63.9% greater in the greenhouse
      systems (98.0 kg N ha-1) than in open-field systems (59.8 kg N ha-1). The
      leaching factor, defined as the proportion of the quantity of N applied to soils
      that was lost due to nitrate leaching, averaged 14.6% overall and was
      significantly lower in greenhouse systems (10.9%) than in open-field systems
      (18.4%). This difference appears to be due to lower of the total water inputs
      (irrigation + precipitation) in greenhouse systems. Nitrate leaching increased
      with water input, the number of growing days, and the N rate. The nitrate
      leaching response to increasing N rate was linear. The leaching factor
      significantly increased with water input but was not affected by the N rate or
      the number of growing days. Compared with application of synthetic fertilizer
      alone, the application of manure alone or manure plus synthetic fertilizer
      significantly reduced both the nitrate leaching and the leaching factor in open
      field and greenhouse systems. These results suggest that nitrate leaching in
      Chinese vegetable systems can be reduced by optimizing rates of N and water
      supply to synchronize crop needs. Application of mixed synthetic N fertilizer and
      manure is more effective in reducing nitrate leaching, compared to synthetic N
      only.

PMID- 30182317
TI  - Plankton community assessment in anthropogenic-impacted oligotrophic coastal
      regions.
AB  - Microbial planktonic communities are critical components of marine biogeochemical
      pathways. Despite this, there is still limited knowledge on the dynamics of this
      group in warm and oligotrophic waters. We used high-throughput sequencing to
      characterise the bacterial (16S rRNA) and eukaryotic (18S rRNA) microbial
      plankton communities in two regions under the influence of anthropogenic impacts
      (a port and sewage outflow) and a coastal region with no direct anthropogenic
      disturbances in the central Red Sea. Overall, bacterial and eukaryotic components
      responded in a similar way to the environmental conditions. Community composition
      and structure were more sensitive than alpha diversity measures to environmental
      impacts. With the exception of eukaryotes, for which the number of OTU differed
      significantly between sampling periods in all the regions, environmental changes
      associated with anthropogenic pressures seem to be better reflected by variations
      in the relative dominance of microbial groups. For example, elevated proportional
      abundances of nitrifying and sewage-/faecal-related bacteria at the impacted
      sites were observed compared with the coastal region. The recently developed
      microgAMBI also appeared to correlate well with the level of anthropogenic impact
      the regions experienced, showing the potential to be applied in oligotrophic
      waters.

PMID- 30182318
TI  - Correction to: Effect of Stimulus Polarity on Detection Thresholds in Cochlear
      Implant Users: Relationships with Average Threshold, Gap Detection, and Rate
      Discrimination.
AB  - The middle initial of Julie G. Arenberg's name was incorrect in the original
      publication; it is correct as displayed here.

PMID- 30182319
TI  - Bleaching of simulated stained-remineralized caries lesions in vitro.
AB  - OBJECTIVE: Non-invasive esthetic treatment options for stained arrested caries
      lesions have not been explored. This study aimed to develop laboratory models to
      create stained-remineralized caries-like lesions (s-RCLs) and to test the
      efficacy of bleaching on their esthetic treatment. MATERIALS AND METHODS: One
      hundred twelve enamel/dentin specimens were prepared from human molars, embedded,
      and had their color measured spectrophotometrically at baseline and after
      demineralization. They were randomly divided into four groups (n = 14) based on
      the staining/remineralization protocols for a total of 5 days: G1, no staining/no
      remineralization; G2, no staining/remineralization in artificial saliva (AS); G3,
      non-metallic staining/remineralization with sodium fluoride/AS; and G4, metallic
      staining/remineralization with silver diamine fluoride/AS. The lesion mineral
      loss (DeltaZ) and depth (L) were measured using transverse microradiography along
      with color change (DeltaE). Specimens were bleached and color was re-evaluated.
      Data were analyzed using ANOVA models followed by Fisher's PLSD tests (alpha =
      0.05). RESULTS: s-RCLs in G4 were significantly (p < 0.001) darker than G3, G2,
      and G1 regardless of substrate type and condition. s-RCLs in G2, G3, and G4
      showed significantly lower DeltaZ and L than G1 (all p < 0.001), confirming
      occurrence of remineralization. G4 exhibited significantly lower DeltaZ and L
      compared to G2 (p < 0.001). Bleaching was more effective in non-metallic than in
      metallic stained lesions regardless of substrate type (p < 0.001). CONCLUSION:
      The proposed models created distinct s-RCLs. Non-metallic s-RCLs were lighter and
      more responsive to bleaching compared to metallic s-RCLs. CLINICAL RELEVANCE: The
      developed experimental models allow the further investigation of the efficacy and
      safety of different clinical strategies for the esthetic management of s-RCLs.

PMID- 30182320
TI  - CMR quantitation of change in mitral regurgitation following transcatheter aortic
      valve replacement (TAVR): impact on left ventricular reverse remodeling and
      outcome.
AB  - Current echocardiographic data reporting the impact of concomitant mitral
      regurgitation (MR) on outcome in patients who undergo transcatheter aortic valve
      replacement (TAVR) are conflicting. Using cardiovascular magnetic resonance (CMR)
      imaging, this study aimed to assess the impact of MR severity on cardiac reverse
      remodeling and patient outcome. 85 patients undergoing TAVR with CMR pre- and 6 m
      post-TAVR were evaluated. The CMR protocol included cines for left (LV) and right
      ventricular (RV) volumes, flow assessment, and myocardial scar assessment by late
      gadolinium enhancement (LGE). Patients were dichotomised according to CMR
      severity of MR fraction at baseline ('non-significant' vs 'significant') and
      followed up for a median duration of 3 years. Forty-two (49%) patients had
      'significant MR' at baseline; they had similar LV and RV size and function
      compared to the 'non-significant MR' group but had greater LV mass at baseline.
      In those with significant MR at baseline, 77% (n = 32) had a reduction in MR post
      TAVR, moving them into the 'non-significant' category at 6-months, with an
      overall reduction in MR fraction from 34 to 17% (p < 0.001). Improvement in MR
      was not associated with more favourable cardiac reverse remodeling when compared
      with the 'non-improvers'. Significant MR at baseline was not associated with
      increased mortality at follow-up. Significant MR is common in patients undergoing
      TAVR and improves in the majority post-procedure. Improvement in MR was not
      associated with more favourable LV reverse remodeling and baseline MR severity
      was not associated with mortality.

PMID- 30182321
TI  - Right ventricular longitudinal strain predicts acute kidney injury and short-term
      prognosis in patients with right ventricular myocardial infarction.
AB  - Right ventricular (RV) systolic dysfunction due to acute myocardial infarction is
      associated with serious complications in the short-term. Acute kidney injury
      (AKI) is a frequent and unrecognized complication. This study aimed to assess
      whether RV longitudinal strain predicts AKI and short-term prognosis in patients
      with RV infarction. Prospective cohort of patients with RV infarction. RV
      function was evaluated with global and free wall right ventricular longitudinal
      strain (GRVLS and FWRVLS), tricuspid annular plane systolic excursion, and
      tricuspid S' wave. The primary endpoint was AKI defined as an increase >= 50% in
      serum creatinine and/or a decrease >= 25% in glomerular filtration rate during
      follow-up at 7 days. The secondary endpoint was death from any cause at 30 days.
      We included 101 patients with RV infarction (male 67%, age 66 +/- 11 years).
      During follow-up at 7 days, 40% of patients developed AKI. At 30 days, 8% of
      patients died. At univariate analysis, FWRVLS was significantly associated with
      AKI (Hazard ratio [HR] 1.11, 95% confidence interval [CI] 1.03-1.20, p = 0.006).
      At multivariate analysis, only age, temporary pacemaker implant, and FWRVLS
      remained as independent predictors of AKI (HR 1.05, 95% CI 1.02-1.08, p = 0.002;
      HR 2.12, 95% CI 1.11-4.07, p = 0.023; HR 1.10, 95% CI 1.02-1.19, p = 0.018,
      respectively). At 30 days, patients with FWRVLS >= - 15.5% showed a lower
      survival rate than those with lower strain (84 +/- 6 vs. 97 +/- 2%, p = 0.021).
      In patients with RV infarction, FWRVLS was an independent predictor of AKI and
      was associated with higher mortality in the short-term.

PMID- 30182322
TI  - Hierarchical Control of Drosophila Sleep, Courtship, and Feeding Behaviors by
      Male-Specific P1 Neurons.
AB  - Animals choose among sleep, courtship, and feeding behaviors based on the
      integration of both external sensory cues and internal states; such choices are
      essential for survival and reproduction. These competing behaviors are closely
      related and controlled by distinct neural circuits, but whether they are also
      regulated by shared neural nodes is unclear. Here, we investigated how a set of
      male-specific P1 neurons controls sleep, courtship, and feeding behaviors in
      Drosophila males. We found that mild activation of P1 neurons was sufficient to
      affect sleep, but not courtship or feeding, while stronger activation of P1
      neurons labeled by four out of five independent drivers induced courtship, but
      only the driver that targeted the largest number of P1 neurons affected feeding.
      These results reveal a common neural node that affects sleep, courtship, and
      feeding in a threshold-dependent manner, and provide insights into how competing
      behaviors can be regulated by a shared neural node.

PMID- 30182323
TI  - The mediating role of the venules between smoking and ischemic stroke.
AB  - A potential mechanism by which smoking affects ischemic stroke is through wider
      venules, but this mediating role of wider venules has never been quantified.
      Here, we aimed to estimate to what extent the effect of smoking on ischemic
      stroke is possibly mediated by the venules via the recently developed four-way
      effect decomposition. This study was part of a population-based study including
      9109 stroke-free persons participated in the study in 1990, 2004, or 2006 (mean
      age: 63.7 years; 58% women). Smoking behavior (smoking versus non-smoking) was
      identified by interview. Retinal venular calibers were measured semi
      automatically on retinal photographs. Incident strokes were assessed until
      January 2016. A regression-based approach was used with venular calibers as
      mediator to decompose the total effect of smoking compared to non-smoking into
      four components: controlled direct effect (neither mediation nor interaction),
      pure indirect effect (mediation only), reference interaction effect (interaction
      only) and mediated interaction effect (both mediation and interaction). During a
      mean follow-up of 12.5 years, 665 persons suffered an ischemic stroke. Smoking
      increased the risk of developing ischemic stroke compared to non-smoking with an
      excess risk of 0.41 (95% confidence interval 0.10; 0.67). With retinal venules as
      a potential mediator, the excess relative risk could be decomposed into 77%
      controlled direct effect, 4% mediation only, 4% interaction only, and 15%
      mediated interaction. To conclude, in the pathophysiology of ischemic stroke, the
      effect of smoking on ischemic stroke may partly explained by changes in the
      venules, where there is both pure mediation and mediated interaction.

PMID- 30182324
TI  - Cancer incidence among Finnish people with type 2 diabetes during 1989-2014.
AB  - Diabetes and cancer are common diseases both with enormous impact on health
      burden globally. The increased risk of several types of cancer among people with
      type 2 diabetes mellitus has been indicated repeatedly. This study aimed at
      exploring and describing the association between type 2 diabetes and cancer
      incidence. A cohort of 428,326 people with type 2 diabetes was identified from
      the Finnish National Diabetes Register and followed up through a register linkage
      with the Finnish Cancer Registry for cancer incidence during 1988-2014. A total
      of 74,063 cases of cancer occurred in this cohort in 4.48 million person-years.
      This accounted for 16% more than the expected cancer incidence in the Finnish
      general population; the standardized incidence ratio (SIR) was 1.16 (95%
      confidence interval [CI] 1.15-1.16). There was a statistically significant excess
      of cancers of lip (SIR = 1.40, CI = 1.28-1.53), liver (SIR = 2.44, CI = 2.35
      2.53), pancreas (SIR = 1.75, CI = 1.70-1.79), stomach (SIR = 1.22, CI = 1.18
      1.26), colon (SIR = 1.22, CI = 1.19-1.25), gallbladder and bile ducts (SIR =
      1.29, CI = 1.21-1.36), non-melanoma skin (SIR = 1.18, CI = 1.15-1.22), kidney
      (SIR = 1.42, CI = 1.37-1.47), bladder (SIR = 1.17, CI = 1.13-1.21), and thyroid
      (SIR = 1.22, CI = 1.12-1.31). There was a small statistically significant
      decrease in prostate cancer incidence (SIR = 0.95, CI = 0.93-0.96). This study
      showed an association between type 2 diabetes mellitus and the incidence of
      cancer at numerous sites in the Finnish population.

PMID- 30182325
TI  - A Novel Molecular Design for a Hybrid Phage-DNA Construct Against DKK1.
AB  - Nucleic acid immunization has recently exhibited a great promise for
      immunotherapy of various diseases. However, it is now clear that powerful
      strategies are imminently needed to improve their efficiency. In this regard,
      whole bacteriophage particles have been described as efficient DNA vaccine
      delivery vehicles, capable of circumventing the limitations of naked DNA
      immunization. Moreover, phage particles could be engineered to display specific
      peptides on their surfaces. Given these inherent characteristics of phages, we
      have designed a novel hybrid phage-DNA immunization vector using both M13 and
      pAAV plasmid elements. Following the construction and in vitro confirmation of
      the designed vectors, they were used for comparative mice immunization, carrying
      the same DNA sequence. The results indicated the efficacy of the designed hybrid
      phage particles, to elicit higher humoral immunity, in comparison to conventional
      DNA-immunization vectors (pCI). In light of these findings, it could be concluded
      that using adeno-associated virus (AAV) expression cassette along with displaying
      TAT peptide on the surface of the phage particle could be deemed as an appealing
      strategy to enhance the DNA-immunization and vaccination efficacy.

PMID- 30182326
TI  - Segmentation of High-Cost Adults in an Integrated Healthcare System Based on
      Empirical Clustering of Acute and Chronic Conditions.
AB  - BACKGROUND: High-cost patients are a frequent focus of improvement projects based
      on primary care and other settings. Efforts to characterize high-cost, high-need
      patients are needed to inform care planning, but such efforts often rely on a
      priori assumptions, masking underlying complexities of a heterogenous population.
      OBJECTIVE: To define recognizable subgroups of patients among high-cost adults
      based on clinical conditions, and describe their survival and future spending.
      DESIGN: Retrospective observational cohort study. PARTICIPANTS: Within a large
      integrated delivery system with 2.7 million adult members, we selected the top 1%
      of continuously enrolled adults with respect to total healthcare expenditures
      during 2010. MAIN MEASURES: We used latent class analysis to identify clusters of
      alike patients based on 53 hierarchical condition categories. Prognosis as
      measured by healthcare spending and survival was assessed through 2014 for the
      resulting classes of patients. RESULTS: Among 21,183 high-cost adults, seven
      clinically distinctive subgroups of patients emerged. Classes included end-stage
      renal disease (12% of high-cost population), cardiopulmonary conditions (17%),
      diabetes with multiple comorbidities (8%), acute illness superimposed on chronic
      conditions (11%), conditions requiring highly specialized care (14%), neurologic
      and catastrophic conditions (5%), and patients with few comorbidities (the
      largest class, 33%). Over 4 years of follow-up, 6566 (31%) patients died, and
      survival in the classes ranged from 43 to 88%. Spending regressed to the mean in
      all classes except the ESRD and diabetes with multiple comorbidities groups.
      CONCLUSIONS: Data-driven characterization of high-cost adults yielded clinically
      intuitive classes that were associated with survival and reflected markedly
      different healthcare needs. Relatively few high-cost patients remain persistently
      high cost over 4 years. Our results suggest that high-cost patients, while not a
      monolithic group, can be segmented into few subgroups. These subgroups may be the
      focus of future work to understand appropriateness of care and design
      interventions accordingly.

PMID- 30182327
TI  - Mechanisms of word concreteness effects in explicit memory: Does context
      availability play a role?
AB  - One explanation for why concrete words are recalled better than abstract words is
      systematic differences across these word types in the availability of context
      information. In contrast, explanations for the concrete-word advantage in
      recognition memory do not consider a possible role for context availability. We
      investigated the extent to which context availability can explain the effects of
      word concreteness in both free recall (Exp. 1) and item recognition (Exp. 2) by
      presenting each target word in isolation, in a low-constraint sentence context,
      or in a high-constraint sentence context at study. Concreteness effects were
      consistent with those from previous research, with concrete-word advantages in
      both tasks. Embedding words in sentence contexts with low semantic constraint
      hurt recall performance but helped recognition performance, relative to
      presenting words in isolation. Embedding words in sentence contexts with high
      semantic constraint hurt both recall and recognition performance, relative to
      words in low-constraint sentences. The effects of concreteness and semantic
      constraint were consistent for both high- and low-frequency words. Embedding
      words in high-constraint sentence contexts neither reduced nor eliminated the
      concreteness effect in recall or recognition, indicating that differences in
      context availability cannot explain concreteness effects in explicit memory.

PMID- 30182328
TI  - Increasing word distinctiveness eliminates the picture superiority effect in
      recognition: Evidence for the physical-distinctiveness account.
AB  - A well-established phenomenon in the memory literature is the picture superiority
      effect-the finding that, all else being equal, memory is better for pictures than
      for words (Paivio & Csapo, 1973). Theorists have attributed pictures' mnemonic
      advantage to dual coding (Paivio, 1971), conceptual distinctiveness (Hamilton &
      Geraci, 2006), and physical distinctiveness (Mintzer & Snodgrass, 1999). Here, we
      present a novel test of the physical-distinctiveness account of picture
      superiority: If the greater physical variability of pictures relative to words is
      responsible for their mnemonic benefit, then increasing the distinctiveness of
      words and/or reducing the physical variability of pictures should reduce or
      eliminate the picture superiority effect. In the present experiments we increased
      word distinctiveness by varying font style, font size, color, and capitalization.
      Additionally, in Experiment 3 we reduced the distinctiveness of pictures by
      presenting black-and-white pictures with similar orientations. In Experiment 4, a
      forced choice procedure was used in which subjects were asked to identify the
      form that each probe had taken during the study phase. The results were
      consistent with the distinctiveness prediction and, notably, were inconsistent
      with dual coding.

PMID- 30182329
TI  - When combined spatial polarities activated through spatio-temporal asynchrony
      lead to better mathematical reasoning for addition.
AB  - Several recent studies have supported the existence of a link between spatial
      processing and some aspects of mathematical reasoning, including mental
      arithmetic. Some of these studies suggested that people are more accurate when
      performing arithmetic operations for which the operands appeared in the lower
      left and upper-right spaces than in the upper-left and lower-right spaces.
      However, this cross-over Horizontality * Verticality interaction effect on
      arithmetic accuracy was only apparent for multiplication, not for addition. In
      these studies, the authors used a spatio-temporal synchronous operand
      presentation in which all the operands appeared simultaneously in the same part
      of space along the horizontal and vertical dimensions. In the present paper, we
      report studies designed to investigate whether these results can be generalized
      to mental arithmetic tasks using a spatio-temporal asynchronous operand
      presentation. We present three studies in which participants had to solve
      addition (Study 1a), subtraction (Study 1b), and multiplication (Study 2) in
      which the operands appeared successively at different locations along the
      horizontal and vertical dimensions. We found that the cross-over Horizontality *
      Verticality interaction effect on arithmetic accuracy emerged for addition but
      not for subtraction and multiplication. These results are consistent with our
      predictions derived from the spatial polarity correspondence account and suggest
      interesting directions for the study of the link between spatial processing and
      mental arithmetic performances.

PMID- 30182331
TI  - Prognostic Impact of Serum Pancreastatin Following Chemoembolization for
      Neuroendocrine Tumors.
AB  - PURPOSE: The objective of this study was to investigate the prognostic impact of
      the biomarker serum pancreastatin in patients with metastatic neuroendocrine
      tumors (NETs) treated with transarterial chemoembolization (TACE). METHODS:
      Patients with metastatic NET treated with TACE at a single institution from 2000
      to 2013 were analyzed. Patient demographics, response to therapy, and long-term
      survival were compared with baseline pancreastatin level and changes in
      pancreastatin levels after TACE. RESULTS: A total of 188 patients underwent TACE
      during the study period. An initial pancreastatin level greater than 5000 pg/mL
      correlated with worse overall survival (OS) from time of first TACE (median OS,
      58.5 vs. 22.1 months, p < 0.001). A decrease in pancreastatin level by 50% or
      more after TACE treatment correlated with improved OS (median OS 53.8 vs. 29.9
      months, p = 0.032). Patients with carcinoid syndrome were more likely to have a
      subsequent increase in pancreastatin after initial drop post-TACE (78.1 vs.
      55.2%, p = 0.002). Patients with an increase in pancreastatin levels after
      initial drop post-TACE were more likely to have liver progression on imaging
      (70.7 vs. 40.7%, p = 0.005) and more likely to need repeat TACE (21.1 vs. 6.7%, p
      = 0.009). CONCLUSIONS: For patients with liver metastases from NET treated with
      TACE, pancreastatin measurement may be a useful prognostic indicator. Extreme
      high levels before TACE can predict poor outcomes, whereas significant drops in
      pancreastatin after TACE correlate with improved survival. An increase in levels
      after initial decrease may predict progressive liver disease requiring repeat
      TACE. As such, pancreastatin levels should be measured throughout the TACE
      treatment period.

PMID- 30182332
TI  - Factors Associated With Host Immune Response and Number of Lymph Nodes: A Large
      Retrospective Cohort Study.
AB  - BACKGROUND: The host immune response (HIR) against tumor cells is one of the key
      players in antitumor activities. However, the relationship between HIR and
      regional lymph nodes (LN) and their impacts on prognosis have not been studied.
      METHODS: This study analyzed HIR and clinicopathologic factors for 8819
      consecutive gastric cancer patients who underwent gastrectomy and D2 LN
      dissection. The findings confirmed Epstein-Barr virus (EBV) with Epstein-Barr
      encoding region in situ hybridization, HIR grading (G1, G2, and G3), LN numbers
      classified into seven groups, and performed ordinal regression analysis. RESULTS:
      The mean number of LNs was 41. A higher degree of HIR was significantly
      associated with male sex, EBV+, non-intestinal histology by Lauren
      classification, earlier American Joint Committee on Cancer (AJCC) stage, and
      greater number of LNs (P < 0.001). Female gender, younger age (< 60 years), EBV+,
      non-intestinal histology, higher HIR grade (G2 and G3), larger tumor size, and
      deeper invasion depth were significantly related to a higher number of LNs, with
      an odds ratio greater than 1. In cancer-specific survival analyses, EBV+, younger
      age, higher HIR grade (G3), and increased number of LNs were independent
      prognostic factors in addition to AJCC stage. CONCLUSIONS: The HIR was associated
      with increased number of LNs was a significant favorable prognosticator.

PMID- 30182333
TI  - Re-sleeve Gastrectomy 4 Years Later: Is It Still an Effective Revisional Option?
AB  - Laparoscopic sleeve gastrectomy (LSG) is the most performed surgical procedure
      worldwide. Long-term outcomes report that up to 30% of patients require
      revisional surgery and re-sleeve gastrectomy (rLSG) is one of the revisional
      procedures available. The aim was to update the outcomes of a cohort of rLSG at
      52 months. This study reports the 52-month follow-up of a cohort of 19 patients
      previously published after 24-month follow-up. Sixteen patients completed the
      follow-up. Nine patients complained of GERD symptoms after 36 months. Five
      patients were converted to laparoscopic RYGB. Two patients were converted to a
      laparoscopic BPD-DS for weight regain 4 patients are asymptomatic with stable
      weight. On the basis of our disappointing results, it can be said that rLSG is
      not currently offered as revisional procedure in both centers.

PMID- 30182334
TI  - Pilot Study of a New Model of Bariatric Surgery: Laparoscopic Intestinal
      Bipartition-Safety and Efficacy Against Metabolic Disorders.
AB  - BACKGROUND: Despite the availability of many gastric surgery techniques to reduce
      obesity and its associated comorbidities, most of these procedures can result in
      life-threatening conditions including lifetime chronic illnesses and death.
      Vertical sleeve gastrectomy and Roux-en-Y gastric bypass have been reported to
      improve obesity-related comorbidities such as T2DM, but the long-term efficacy of
      these two procedures is unknown, and their significant impact on long-term weight
      loss was diminished by complications as reported in previous studies. Recently,
      laparoscopic biliopancreatic diversion with duodenal switch (BPD/DS) was
      developed to achieve sustained weight loss (Buchwald et al. Am J Med. 122:248-56,
      2009; Sjostrom et al. N Engl J Med. 351:2683-93, 2004) as well as an improvement
      in comorbid conditions, such as T2DM and hypertension (Buchwald et al. in Am J
      Med. 122:248-56, 2009; Dorman et al. Surgery. 152:758-65, 2012). The
      malabsorptive strategy of bypassing portions of the small intestine and
      delivering nutrients directly to the ileum may promote weight loss by enhanced
      activation of a negative feedback mechanism known as the "ileal brake" (Naslund
      et al. J Gastrointest Surg. 5:556-67, 2001). The purpose of this pilot study was
      to evaluate the safety, reproducibility, and efficiency of a new surgical
      bariatric model of laparoscopic intestinal bipartition (LIB) in patients with a
      BMI between 35 and 40 kg/m2. The setting was in university hospitals. METHODS:
      Between January 2011 and September 2012, seven patients were enrolled in the
      study and underwent the LIB procedure. One patient was operated by LIB for morbid
      obesity with comorbidities, especially T2DM, without any previous bariatric or
      gastric surgery. Six patients underwent the surgery after a sleeve gastrectomy
      for >= 4 years with a recurrence of obesity and diabetes. RESULTS: The
      comorbidity factors decreased to the normal values in all patients at 6 months, 1
      year, and 5 years postoperatively. The percentage of total weight loss was 21.1%
      at 6 months, 22.6% at 1 year, and 15.6% at 5 years. Weight excess was
      significantly lower at 6-month, 1-year, and 5-year postoperatively compared with
      baseline (p < 0.001). Comparison of comorbidity values at 6 months, 1 year, and 5
      years did not show any significant differences. CONCLUSION: Laparoscopic
      intestinal bipartition produced a total recovery from obesity-related
      comorbidities, especially T2DM and EWL without any signs of nutritional
      deficiency, although the 5-year follow-up is ongoing in order to demonstrate the
      efficacy and long-term durability of this procedure.

PMID- 30182335
TI  - Response to Letter of "Left Gastric Artery Embolization for Weight Loss-a Deadend
      Procedure".

PMID- 30182336
TI  - Polyglutamine Repeats in Viruses.
AB  - This review explores the presence and functions of polyglutamine (polyQ) in viral
      proteins. In mammals, mutations in polyQ segments (and CAG repeats at the
      nucleotide level) have been linked to neural disorders and ataxias. PolyQ regions
      in normal human proteins have documented functional roles, in transcription
      factors and, more recently, in regulating autophagy. Despite the high frequency
      of polyQ repeats in eukaryotic genomes, little attention has been given to the
      presence or possible role of polyQ sequences in virus genomes. A survey described
      here revealed that polyQ repeats occur rarely in RNA viruses, suggesting that
      they have detrimental effects on virus replication at the nucleotide or protein
      level. However, there have been sporadic reports of polyQ segments in potyviruses
      and in reptilian nidoviruses (among the largest RNA viruses known). Conserved
      polyQ segments are found in the regulatory control proteins of many DNA viruses.
      Variable length polyQ tracts are found in proteins that contribute to
      transmissibility (cowpox A-type inclusion protein (ATI)) and control of latency
      (herpes viruses). New longer-read sequencing methods, using original biological
      samples, should reveal more details on the presence and functional role of polyQ
      in viruses, as well as the nucleotide regions that encode them. Given the known
      toxic effects of polyQ repeats, the role of these segments in neurovirulent and
      tumorigenic viruses should be further explored.

PMID- 30182330
TI  - Aberrant miRNAs Regulate the Biological Hallmarks of Glioblastoma.
AB  - GBM is the highest incidence in primary intracranial malignancy, and it remains
      poor prognosis even though the patient is gave standard treatment. Despite
      decades of intense research, the complex biology of GBM remains elusive. In view
      of eight hallmarks of cancer which were proposed in 2011, studies related to the
      eight biological capabilities in GBM have made great progress. From these
      studies, it can be inferred that miRs, as a mode of post-transcriptional
      regulation, are involved in regulating these malignant biological hallmarks of
      GBM. Herein, we discuss state-of-the-art research on how aberrant miRs modulate
      the eight hallmarks of GBM. The upregulation of 'oncomiRs' or the genetic loss of
      tumor suppressor miRs is associated with these eight biological capabilities
      acquired during GBM formation. Furthermore, we also discuss the applicable
      clinical potential of these research results. MiRs may aid in the diagnosis and
      prognosis of GBM. Moreover, miRs are also therapeutic targets of GBM. These
      studies will develop and improve precision medicine for GBM in the future.

PMID- 30182337
TI  - Cellular Proteostasis in Neurodegeneration.
AB  - The term proteostasis reflects the fine-tuned balance of cellular protein levels,
      mediated through a vast network of biochemical pathways. This requires the
      regulated control of protein folding, post-translational modification, and
      protein degradation. Due to the complex interactions and intersection of
      proteostasis pathways, exposure to stress conditions may lead to a disruption of
      the entire network. Incorrect protein folding and/or modifications during protein
      synthesis results in inactive or toxic proteins, which may overload degradation
      mechanisms. Further, a disruption of autophagy and the endoplasmic reticulum
      degradation pathway may result in additional cellular stress which could
      ultimately lead to cell death. Neurodegenerative diseases such as Parkinson's
      disease, Alzheimer's disease, Huntington's disease, and Amyotrophic Lateral
      Sclerosis all share common risk factors such as oxidative stress, aging,
      environmental stress, and protein dysfunction; all of which alter cellular
      proteostasis. The differing pathologies observed in neurodegenerative diseases
      are determined by factors such as location-specific neuronal death, source of
      protein dysfunction, and the cell's ability to counter proteotoxicity. In this
      review, we discuss how the disruption in cellular proteostasis contributes to the
      onset and progression of neurodegenerative diseases.

PMID- 30182338
TI  - Disorders of Humoral Immunity in Children with IgG Subclass Deficiency and
      Recurrent Respiratory Infections.
AB  - Respiratory tract infections in children are one of the most common causes for
      medical consultations. When the infections are of recurring nature, they are a
      major reason for the diagnostics for primary immunodeficiency that is in about
      65% of cases underlain by disorders of humoral immunity. This study seeks to
      retrospectively evaluate the history of recurrent respiratory tract infections in
      children with humoral disorders and the associations among deficiencies in the
      immune system components. We evaluated 394 children aged 3 months to 18 years. We
      found 49.5% (195 cases) of children with IgG deficiencies, all of whom had normal
      IgE levels. There were 8.4% (33 cases) of IgA deficiency, 7.4% (29 cases) of IgM
      insufficiency, and 4.1% (16 cases) of CD19+ cells deficiency. The elevated level
      of CD19+ cells was found in 27.7% (109 out of the 394 children). Immunoglobulin
      deficiencies often coexisted with a deficiency in another immunoglobulin class
      above outlined. There was an interdependence between IgA abnormality and IgG,
      IgG3, and IgG4 abnormalities as well as between IgM abnormality and IgG and IgG1
      abnormalities. We conclude that respiratory tract infections in children are
      often underlain by a convergence of IgG with both IgA and IgM abnormal states.
      The physiopathological meaning of this convergence for the infection course and
      resulting functional respiratory changes remains elusive.

PMID- 30182339
TI  - In silico screening for ERalpha down modulators identifies thioridazine as an
      anti-proliferative agent in primary, 4OH-tamoxifen-resistant and Y537S ERalpha
      expressing breast cancer cells.
AB  - PURPOSE: Most breast cancers (BCs) express estrogen receptor alpha (ERalpha) and
      are treated with the endocrine therapy (ET) drugs 4OH-tamoxifen (Tam) and
      fulvestrant (ICI 182,780; ICI). Unfortunately, a high fraction of ET treated
      women relapses and becomes resistant to ET. Therefore, additional anti-BC drugs
      are needed. Recently, we proposed that the identification of novel anti-BC drugs
      can be achieved using modulation of the intracellular ERalpha content in BC cells
      as a pharmacological target. Here, we searched for Food and Drug Administration
      (FDA)-approved drugs that potentially modify the ERalpha content in BC cells.
      METHODS: We screened in silico more than 60,000 compounds to identify FDA
      approved drugs with a gene signature similar to that of ICI. We identified
      mitoxantrone and thioridazine and tested them in primary, Tam-resistant and
      genome-edited Y537S ERalpha-expressing BC cells. RESULTS: We found that
      mitoxantrone and thioridazine induced ERalpha downmodulation and prevented MCF-7
      BC cell proliferation. Interestingly, while mitoxantrone was found to be toxic
      for normal breast epithelial cells, thioridazine showed a preferential activity
      towards BC cells. Thioridazine also reduced the ERalpha content and prevented
      cell proliferation in primary, Tam-resistant and genome-edited Y537S ERalpha
      expressing BC cells. CONCLUSIONS: We suggest that modulation of the intracellular
      ERalpha concentration in BC cells can be exploited in in silico screens to
      identify anti-BC drugs and uncover a re-purposing opportunity for thioridazine in
      the treatment of primary and metastatic ET resistant BCs.

PMID- 30182340
TI  - CXCL12 expression is a bona fide predictor of recurrence in lung neuroendocrine
      tumours; a multicentric study with emphasis on atypical carcinoids - a short
      report.
AB  - PURPOSE: Neuroendocrine tumors of the lung (LNETs) encompass a heterogeneous
      group of lesions, including tumors with no or low metastatic potential, such as
      typical (TCs) and atypical (ACs) carcinoids, and highly aggressive neuroendocrine
      carcinomas. To date, only a few biomarkers with prognostic impact have been
      identified in LNETs. Previous experimental studies have suggested that the
      cytokine CXCL12 might have a role in stratifying the outcome of lung cancer as
      well as LNET patients. However, the reliability of immunohistochemical (IHC)
      tissue expression of CXCL12 in evaluating the prognosis of resected LNETs is
      currently not known. METHODS: Here, we subjected a cohort of 112 resected LNETs
      specifically enriched for ACs to IHC for CXCL12 and Ki67 using routine
      procedures. The clinical value of CXCL12 was assessed by applying the Cox
      proportional-hazards model to overall and disease-free survival rates. RESULTS:
      We found that CXCL12 was expressed in 8.3 to 38% of LNETs, depending on the
      different diagnostic categories. Upon survival analysis, when considering the
      whole cohort, we found that CXCL12-positive cases exhibited shorter disease-free
      survival rates compared to CXCL12-negative cases. Among ACs, tumors
      overexpressing CXCL12 showed significantly shorter disease-free survival rates.
      Finally, we found that the Ki67 index in ACs was higher in the CXCL12-positive
      cases. CONCLUSION: CXCL12 immunohistochemistry may serve as a potentially useful
      tool to better stratify LNETs, and more specifically ACs, in clinical practice.

PMID- 30182341
TI  - Radio-sensitization of head and neck cancer cells by a combination of poly(I:C)
      and cisplatin through downregulation of survivin and c-IAP2.
AB  - PURPOSE: Head and neck squamous cell carcinoma (HNSCC) is one of the most common
      cancers. Concurrent radio-chemotherapy is the standard of care for advanced
      tumors. However, there is a need for more efficient regimens with less side
      effects resulting from high doses. Therefore, we set out to explore the
      therapeutic potential of ternary combinations by bringing together irradiation,
      cis-platinum and a TLR3 agonist, poly(I:C), with the aim to reduce the dosage of
      each treatment. This approach is based on our previous work, which revealed a
      selective cytotoxic effect of TLR3 agonists against malignant cells when combined
      with other anti-neoplastic agents. METHODS: We explored the survival of HNSCC
      derived cells (Detroit 562, FaDu, SQ20B and Cal27) using MTT and caspase 3/7
      activation assays. The radio-sensitization effects of poly(I:C) and cisplatin
      were assessed using Western blotting, cell cycle progression, ROS formation and
      qRT-PCR assays. RESULTS: We found that the combination of poly(I:C) and cisplatin
      downregulated c-IAP2 and survivin expression, reduced cell survival, induced anti
      apoptotic gene expression and apoptosis, increased ROS formation and induced G2/M
      cell cycle arrest in the HNSCC-derived cells tested. CONCLUSIONS: Our results
      indicate that a combined poly(I:C) and cisplatin treatment reduces the survival
      and induces the radio-sensitivity of HNSCC-derived cells, thus providing a
      rationale for the development of novel strategies for the treatment of head and
      neck cancer.

PMID- 30182342
TI  - Clopidogrel Versus Newer P2Y12 Antagonists for Percutaneous Coronary Intervention
      in Patients with Out-of-Hospital Cardiac Arrest Managed with Therapeutic
      Hypothermia: A Meta-Analysis.
AB  - INTRODUCTION: The impact of therapeutic hypothermia (TH) on outcomes of
      percutaneous coronary intervention (PCI) and the optimal antiplatelet treatment
      remains debatable. METHODS: Electronic databases were searched for randomized
      trials and observational studies to evaluate the available clinical evidence
      comparing the use of clopidogrel versus newer P2Y12 antagonists in cases of TH
      after PCI. The primary outcome was in-hospital definite stent thrombosis while
      the secondary outcomes were in-hospital mortality and major bleeding. Fixed
      effects risk ratios (RRs) were estimated using Mantel-Haenszel method. RESULTS:
      The final analysis included five studies with a total of 290 patients. There was
      no difference in the incidence of stent thrombosis (RR 0.92; 95% CI 0.35-2.38),
      in-hospital mortality (RR 1.38; 95% CI 0.72-2.65), and major bleeding (RR 0.89;
      95% CI 0.33-2.40) between patients receiving clopidogrel versus those receiving
      newer agents. CONCLUSIONS: This meta-analysis showed no difference between
      clopidogrel and newer antiplatelet agents in the incidence of stent thrombosis or
      in-hospital mortality for PCI in cases of TH. Further randomized studies are
      needed to explore the optimal dual antiplatelet treatment in TH.

PMID- 30182343
TI  - A bone in the heart: the strange case of Pope Urban VIII.

PMID- 30182345
TI  - High Healthcare Resource Use in Hospitalized Patients with a Diagnosis of Spinal
      Muscular Atrophy Type 1 (SMA1): Retrospective Analysis of the Kids' Inpatient
      Database (KID).
AB  - BACKGROUND: Patients with spinal muscular atrophy (SMA) have high healthcare
      resource use (HRU) due to respiratory and nutritional complications resulting
      from progressive muscle atrophy. While previous studies estimate the direct costs
      to be US$113,000 to US$121,682 per year in the US, they potentially understate
      costs for type 1 SMA (SMA1). This study analyzed HRU in hospitalizations with a
      diagnosis of SMA1 and compared it with hospitalizations with complex chronic
      conditions (CCC) other than SMA1 or those with no CCC. METHODS: This
      retrospective analysis of a defined subset of the 2012 Kids' Inpatient Database
      (KID) compared a nationally estimated number of hospitalizations of children
      (aged < 3 years) categorized into three groups: (1) SMA1 (n = 237 admissions),
      (2) no CCC (n = 632,467 admissions), and (3) other CCC (n = 224,953 admissions).
      RESULTS: Mean total charges were higher for SMA1 admissions compared with
      admissions with no CCC (US$150,921 vs US$19,261 per admission, respectively;
      costs: US$50,190 vs $5862 per admission, respectively; both p < 0.0001). A larger
      proportion of SMA1 admissions were billed for one or more procedure codes (81.9%)
      than in the no CCC group (39.4%) or other CCC group (70.1%; both p <= 0.0003).
      SMA1 admissions had a longer length of stay compared with admissions with no CCC
      (15.1 vs 3.4, respectively; p < 0.0001). CONCLUSIONS: The average total charges
      for a single SMA1 admission were higher than those of the no CCC group. Because
      most infants with SMA1 require multiple hospitalizations per year, previous
      estimates may dramatically underestimate the direct costs associated with HRU.
      Further studies are required to determine the indirect costs and societal impacts
      of SMA1.

PMID- 30182346
TI  - Value Assessment Frameworks in the United States: A Call for Patient Engagement.

PMID- 30182344
TI  - Cellulose-based hydrogel materials: chemistry, properties and their prospective
      applications.
AB  - Hydrogels based on cellulose comprising many organic biopolymers including
      cellulose, chitin, and chitosan are the hydrophilic material, which can absorb
      and retain a huge proportion of water in the interstitial sites of their
      structures. These polymers feature many amazing properties such as responsiveness
      to pH, time, temperature, chemical species and biological conditions besides a
      very high-water absorption capacity. Biopolymer hydrogels can be manipulated and
      crafted for numerous applications leading to a tremendous boom in research during
      recent times in scientific communities. With the growing environmental concerns
      and an emergent demand, researchers throughout the globe are concentrating
      particularly on naturally derived hydrogels due to their biocompatibility,
      biodegradability and abundance. Cellulose-based hydrogels are considered as
      useful biocompatible materials to be used in medical devices to treat, augment or
      replace any tissue, organ, or help function of the body. These hydrogels also
      hold a great promise for applications in agricultural activity, as smart
      materials and some other useful industrial purposes. This review offers an
      overview of the recent and contemporary research regarding physiochemical
      properties of cellulose-based hydrogels along with their applications in
      multidisciplinary areas including biomedical fields such as drug delivery, tissue
      engineering and wound healing, healthcare and hygienic products as well as in
      agriculture, textiles and industrial applications as smart materials.

PMID- 30182347
TI  - Cardiovascular disease in chronic myelomonocytic leukemia: do monocytosis and
      chronic inflammation predispose to accelerated atherosclerosis?
AB  - Patients with chronic myelomonocytic leukemia (CMML) have monocytosis and likely
      a state of chronic inflammation. Both have been associated with an increased risk
      of atherosclerosis. The aim of the study was to test the hypothesis that CMML
      patients are at increased risk of developing cardiovascular disease (CVD) due to
      persistent monocytosis and sustained chronic inflammation. In a retrospective
      cohort study, we assessed hazards for cardiovascular events after diagnosis in
      112 CMML patients and 231 chronic lymphocytic leukemia (CLL) patients. Analyses
      were carried out on restricted cohorts (CMML = 84, CLL = 186), excluding patients
      with a prior history of CVD, as well as on unrestricted cohorts. In the
      restricted cohorts, a significant effect of cardiovascular event occurrence did
      not remain after adjustment (HR 2.49, 95% CI 0.94-6.60). In unrestricted cohorts,
      we found a more than twofold increased rate of cardiovascular events in CMML (HR
      2.34, 95% CI 1.05-5.20). Our results indicate an increased risk of CVD after the
      diagnosis in CMML patients.

PMID- 30182348
TI  - Secondary diffuse large B cell lymphoma of the central nervous system:
      retrospective review of case series.

PMID- 30182350
TI  - Efficacy and Safety of the Use of Non-vitamin K Antagonist Oral Anticoagulants in
      Patients with Ischemic Heart Disease: A Meta-Analysis of Phase III Randomized
      Trials.
AB  - BACKGROUND: There are conflicting published data on non-vitamin K antagonist oral
      anticoagulants (NOACs), with varying evidence of benefit or harm in acute
      coronary syndrome (ACS) and non-ACS cohorts. To explore the efficacy and safety
      of NOAC use in patients with ischemic heart disease (IHD), we conducted a meta
      analysis of phase III randomized controlled trials (RCTs). METHODS: We
      systematically searched the Cochrane Library, PubMed, and Embase databases. A
      random-effect model was selected to pool the effect measurement estimates (hazard
      ratios [HRs] and 95% confidence intervals [CIs]). RESULTS: Three RCTs with 39,492
      enrolled IHD patients were included. Compared with placebo, NOACs were associated
      with reduced risks of major adverse cardiac events (MACE) (HR 0.83, 95% CI 0.76
      0.90), cardiovascular death (HR 0.82, 95% CI 0.72-0.93), and myocardial
      infarction (HR 0.87, 95% CI 0.78-0.97) accompanied by increased risks of major
      bleeding (HR 2.46, 95% CI 1.42-4.26), but not fatal bleeding (HR 1.35, 95% CI
      0.76-2.39) or intracranial hemorrhage (HR 2.19, 95% CI 0.91-5.27). Subgroup
      analysis revealed that NOACs were associated with an increased risk of major
      bleeding in patients who received dual antiplatelet therapy compared with
      patients who received single antiplatelet therapy (3.01, 1.82-4.98 vs. 1.66, 1.37
      2.03; P for interaction 0.03) and patients with ACS compared with patients with
      non-ACS (3.27, 2.16-4.95 vs. 1.66, 1.36-2.02; P for interaction 0.004).
      CONCLUSIONS: In patients with IHD, NOACs confer protection against thrombosis
      related complications, but at the cost of an increased hazard of major bleeding.
      NOACs plus a single antiplatelet drug seem to be a good choice for patients with
      IHD.

PMID- 30182351
TI  - Adult outcomes of conduct problems in childhood or adolescence: further evidence
      of the societal burden of conduct problems.

PMID- 30182352
TI  - Effects of Nutritional Deficiency of Boron on the Bones of the Appendicular
      Skeleton of Mice.
AB  - Scientific evidence has shown the nutritional importance of boron (B) in the
      remodeling and repair of cancellous bone tissue. However, the effects of the
      nutritional deficiency of B on the cortical bone tissue of the appendicular
      skeleton have not yet been described. Thus, a study was performed to
      histomorphometrically evaluate the density of osteocyte lacunae of cortical bone
      of mouse femora under conditions of nutritional deficiency of B and to analyze
      the effects of the deficiency on the biomechanical properties of mouse tibiae.
      Weaning, 21-day-old male Swiss mice were assigned to the following two groups:
      controls (B+; n = 10) and experimental (B-; n = 10). Control mice were fed a
      basal diet containing 3 mg B/kg, whereas experimental mice were fed a B-deficient
      diet containing 0.07 mg B/kg for 9 weeks. The histological and histomorphometric
      evaluations of the mice fed a B-deficient diet showed a decrease in the density
      of osteocyte lacunae in the femoral cortical bone tissue and the evaluation of
      biomechanical properties showed lower bone rigidity in the tibia.

PMID- 30182353
TI  - Correction to: Investigation and Comparison of In Vitro Genotoxic Potency of PM10
      Collected in Rural and Urban Sites at Tehran in Different Metrological Conditions
      and Different Seasons.
AB  - The original version of this article unfortunately contained a mistake. Figure 6
      caption should be "The light microscopic image (a) and transmission electron
      microscopic image (b) of A549 cell after 24 h of exposure to PM10 (150 MUg/ml).

PMID- 30182349
TI  - Oncoplastic Breast Consortium consensus conference on nipple-sparing mastectomy.
AB  - PURPOSE: Indications for nipple-sparing mastectomy (NSM) have broadened to
      include the risk reducing setting and locally advanced tumors, which resulted in
      a dramatic increase in the use of NSM. The Oncoplastic Breast Consortium
      consensus conference on NSM and immediate reconstruction was held to address a
      variety of questions in clinical practice and research based on published
      evidence and expert panel opinion. METHODS: The panel consisted of 44 breast
      surgeons from 14 countries across four continents with a background in
      gynecology, general or reconstructive surgery and a practice dedicated to breast
      cancer, as well as a patient advocate. Panelists presented evidence summaries
      relating to each topic for debate during the in-person consensus conference. The
      iterative process in question development, voting, and wording of the
      recommendations followed the modified Delphi methodology. RESULTS: Consensus
      recommendations were reached in 35, majority recommendations in 24, and no
      recommendations in the remaining 12 questions. The panel acknowledged the need
      for standardization of various aspects of NSM and immediate reconstruction. It
      endorsed several oncological contraindications to the preservation of the skin
      and nipple. Furthermore, it recommended inclusion of patients in prospective
      registries and routine assessment of patient-reported outcomes. Considerable
      heterogeneity in breast reconstruction practice became obvious during the
      conference. CONCLUSIONS: In case of conflicting or missing evidence to guide
      treatment, the consensus conference revealed substantial disagreement in expert
      panel opinion, which, among others, supports the need for a randomized trial to
      evaluate the safest and most efficacious reconstruction techniques.

PMID- 30182355
TI  - Identification of Effective Dimeric Gramicidin-D Peptide as Antimicrobial
      Therapeutics over Drug Resistance: In-Silico Approach.
AB  - Discovering and developing the antimicrobial peptides are recently focused on
      pharmaceutical firm, since they serve as complementary to antibiotics in
      prevailing over drug resistance by eliciting the disruption of microbial
      membrane. Still, there are lots of challenges to bring up the structurally stable
      and functionally efficient antimicrobial peptides. It is well known that
      gramicidin D is the prominent antimicrobial peptide that exists as g-AB, g-BC,
      and g-AC. This study analyzes the structural stability and the functional
      activity of hetero-dimeric double-stranded gramicidin-D peptides, thereby
      demonstrating its potent antimicrobial activity against antibiotic-resistant
      micro-organisms. To investigate the structural stability and functionality of
      gramicidin D, we performed static and dynamic analysis. Initially, we observed a
      maximum number of intermolecular interactions and membrane penetration in g-AB as
      compared to g-BC and g-AC. To substantiate further, the geometrical and
      thermodynamic parameters revealed the retention of maximum stability in g-AB than
      g-AC and g-BC. Thus, the conformational free energy and the binding free energy
      showed the variation among gramicidin-D peptides for the prediction of increased
      stability and functionality. In conclusion, g-AB peptide has definitely
      demonstrated adequate structural stability and functionality and this work will
      need to be considered in peptide-based drug discovery.

PMID- 30182354
TI  - From Biological Determination to Entangled Causation.
AB  - Biologists and philosophers often use the language of determination in order to
      describe the nature of developmental phenomena. Accounts in terms of
      determination have often been reductionist. One common idea is that DNA is
      supposed to play a special explanatory role in developmental explanations,
      namely, that DNA is a developmental determinant. In this article we try to make
      sense of determination claims in developmental biology. Adopting a
      manipulationist approach, we shall first argue that the notion of developmental
      determinant is causal. We suggest that two different theses concerning
      developmental determination can be articulated: determination of occurrence and
      structural determination. We shall argue that, while the first thesis is
      problematic, the second, opportunely qualified, is feasible. Finally, we shall
      argue that an analysis of biological causation in terms of determination cannot
      account for entangled dynamics. Characterising causal entanglement as a
      particular kind of interactive causation whereby difference-making causes
      ascribable to different levels of biological organisation influence a particular
      ontogenetic outcome, we shall, via two illustrative examples, diagnose some
      potential limits of a reductionist, molecular and intra-level understanding of
      biological causation.

PMID- 30182356
TI  - Mitral valve repair in Barlow's disease by chordal reconstruction using the
      adjustable slip-knot technique.
AB  - The adjustable slip-knot technique-a procedure for facilitating repair of the
      mitral valve prolapse-was first performed and reported by us in 2015. This
      technique comprises six steps: anchor institution in the papillary muscle,
      flexible band positioning, saline injection to confirm the prolapsing site,
      neochorda setting between the anchor and leaflet, fine adjustment of the
      neochordal length, and knot-fixing to confirm repair. Here, we have described the
      first case of successful mitral valve repair using the adjustable slip-knot
      technique in a 51-year-old man with Barlow's disease.

PMID- 30182357
TI  - Correction to: Processing and Analyzing Human Microbiome Data.
AB  - The original version of this chapter was inadvertently published without
      including the dbGaP acknowledgment. The updated chapter now contains that
      information.

PMID- 30182358
TI  - The Effect of Alginate in Gastroesophageal Reflux in Infants.
AB  - BACKGROUND: Guidelines are contradictory regarding the use of alginate in infants
      with persisting gastroesophageal reflux (GER). While The British National
      Institute for Health and Care (NICE) guidelines consider alginate as a treatment
      option, the guidelines of the European and North-American Societies for Pediatric
      Gastroenterology, Hepatology and Nutrition (ESPGHAN, NASPGHAN) do not recommend
      alginates. AIMS: We assessed the efficacy of alginate to reduce GER episodes in
      infants. METHODS: In a prospective, observational study, we consecutively
      enrolled all infants referred for pH-multiple intraluminal impedance (pH-MII)
      recording because of persisting GER symptoms not responsive to behavior and
      dietetic modifications. A 48-h pH-MII was performed in all infants; a baseline
      recording was performed during the first 24 h while magnesium or sodium alginate
      was administered during the second 24 h. The primary endpoint was the difference
      in the total number of GER episodes per 24 h between the baseline day and the
      second day during which the alginate was administered. The secondary outcome was
      the difference in symptoms between each period. We also compared other pH-MII
      data from before and during alginate administration. RESULTS: We recruited 43
      infants (median age 68 days, range 25-306); three pH-MII tracings were excluded
      because of artifacts. The median number of all MII reflux episodes was
      significantly reduced during alginate administration (76.0 vs 69.5; p < 0.001).
      Crying-fussiness, cough and regurgitation episodes all significantly improved
      during alginate administration (p = 0.00012; p = 0.005 and p = 0.04,
      respectively). The following MII parameters also decreased during the alginate
      administration: acid (19.0 vs 14.5; p < 0.04), non-acid (52.0 vs 49.5; p <
      0.004), proximal GER episodes (46.0 vs 41.4; p < 0.007), and bolus exposure index
      (1.9 vs 1.6; p = 0.002). At least three out of seven pH-MII parameters decreased
      by > 10% during the alginate period in 31/40 infants (77.5%), without a
      significant difference between magnesium and sodium alginate. CONCLUSION: These
      results suggest that alginate significantly decreases the number and extension of
      both acid and non-acid reflux episodes and associated symptoms in infants.

PMID- 30182359
TI  - Effects of selenium and vitamin C on the serum level of antithyroid peroxidase
      antibody in patients with autoimmune thyroiditis.
AB  - PURPOSE: Selenium (Se), an essential trace element, has been implicated in
      pathogenesis of autoimmune thyroiditis (AIT). Most studies attributed the immune
      modulating effects of Se to its antioxidant properties. However, there is
      insufficient evidence to support the use of selenium supplementation or other
      antioxidants in patients with AIT. This clinical trial was designed to
      investigate the impact of Se and vitamin C supplementation on antithyroid
      peroxidase antibody (TPO-Ab) level in patients with AIT. METHODS: One hundred and
      two subjects aged 15-78 years were randomized into three groups. Group one (GI)
      (n = 38) was treated with 200 MUg/day sodium selenite, group two (GII) (n = 36)
      received 500 mg vitamin C/day, and group three (GIII) (n = 28) received placebo
      over a 3-month period. Thyroid stimulating hormone (TSH), TPO-Ab,
      antithyroglobulin antibody (Tg-Ab) and Se concentrations were once measured
      before treatment and at the end of the study. RESULTS: After 3 months, TPO-Ab
      concentrations decreased within Se and vitamin C-treated groups, but did not
      change in the placebo subjects. In this regard, there was no significant
      difference between the groups. We also did not find any statistically significant
      difference in TSH and Tg-Ab levels within and between the groups. At the end of
      the study, Se level was significantly higher in GI compared with GII and GIII.
      CONCLUSION: Our findings supported the hypothesis of antioxidant beneficial
      effects of Se in AIT. However, it was not superior to vitamin C, regarding its
      effects on thyroid-specific antibodies.

PMID- 30182360
TI  - Thyroid nodule recurrence following lobo-isthmectomy: incidence, patient's
      characteristics, and risk factors.
AB  - PURPOSE: This study was aimed at assessing the incidence and timing of thyroid
      nodules recurrence, defined as appearance of new benign or malignant nodules in
      contralateral lobe in patients with benign thyroid nodules or thyroid
      microcarcinoma treated with lobo-isthmectomy. Patient's characteristics and risk
      factors associated with this phenomenon were also investigated. METHODS: A
      retrospective study was performed by evaluating 413 patients undergoing lobo
      isthmectomy with a minimum follow-up of 1 year. Clinical characteristics,
      surgical interventions and complications, histological diagnosis, and thyroid
      function at last follow-up were collected. RESULTS: Single or multiple thyroid
      nodule recurrence equally occurred in 80 patients (23%) with a median time to
      relapse of ~ 5 years (range 0.3-34.5 years) after lobo-isthmectomy. Recurrence
      was significantly associated with younger age (< 46 years) and number of
      pregnancies in women. Development of hypothyroidism was not rare either (~ 10%)
      and appeared in 3-19 months; a preoperative TSH level > 2.43 mIU/L was associated
      with the need of l-thyroxin replacement therapy after surgery. The most frequent
      surgical complication was transient hypoparathyroidism (4.6%), while the rate of
      permanent hypoparathyroidism significantly increased in patients submitted to
      completion thyroidectomy (5.3%). CONCLUSIONS: Thyroid nodules recurrence
      following lobo-isthmectomy is not a rare event and occurs within 5 years after
      surgery, more frequently in younger patients with family history of nodular
      goiter and in women with multiple pregnancies. Pre-surgical TSH levels may
      predict the development of post-surgical hypothyroidism, possibly improving the
      management of patients addressed to surgery.

PMID- 30182361
TI  - Peripheral T and B lymphocytes do not correlate with Graves' orbitopathy.

PMID- 30182362
TI  - Correction to: Baseline characteristics and patterns of care in testicular cancer
      patients: first data from the Swiss Austrian German Testicular Cancer Cohort
      Study (SAG TCCS).

PMID- 30182363
TI  - New drug candidates for depression - a nationwide population-based study.
AB  - OBJECTIVE: To investigate whether continued use of non-aspirin NSAID, low-dose
      aspirin, high-dose aspirin, statins, allopurinol and angiotensin agents decreases
      the rate of incident depression using Danish nationwide population-based
      registers. METHODS: All persons in Denmark who purchased the exposure medications
      of interest between 1995 and 2015 and a random sample of 30% of the Danish
      population was included in the study. Two different outcome measures were
      included, (i) a diagnosis of depressive disorder at a psychiatric hospital as in
      patient or out-patient and (ii) a combined measure of a diagnosis of depression
      or use of antidepressants. RESULTS: A total of 1 576 253 subjects were exposed to
      one of the six drugs of interest during the exposure period from 2005 to 2015.
      Continued use of low-dose aspirin, statins, allopurinol and angiotensin agents
      was associated with a decreased rate of incident depression according to both
      outcome measures. Continued uses of non-aspirin NSAIDs as well as high-dose
      aspirin were associated with an increased rate of incident depression.
      CONCLUSION: The findings support the potential of agents acting on inflammation
      and the stress response system in depression as well as the potential of
      population-based registers to systematically identify drugs with repurposing
      potential.

PMID- 30182364
TI  - Eric A. Barnard FRS (1927-2018).

PMID- 30182365
TI  - Pharmacological evaluation of Convolvulus pluricaulis as hypolipidaemic agent in
      Triton WR-1339-induced hyperlipidaemia in rats.
AB  - OBJECTIVE: The aim of the study was to evaluate the effect of Convolvulus
      pluricaulis (CP; C. pluricaulis) methanolic extract on Triton WR-1339-induced
      hyperlipidaemia in rats. METHODS: The study comprised of six groups namely normal
      control, experimental control and treatment groups (100, 200 and 400 mg/kg of C.
      pluricaulis, and 65 mg/kg of Fenofibrate). Hyperlipidaemia was induced by a
      single intraperitoneal injection of Triton WR-1339 400 mg/kg in rats. Parameters
      such as lipid profile, oxidative stress, histological analysis and atherogenic
      index were evaluated. The plant extract was further studied by HPLC and LCMS, for
      analyses of active phytochemicals. KEY FINDINGS: The result of the study showed
      that C. pluricaulis significantly decreased total cholesterol, triglycerides, LDL
      c, MDA levels and atherogenic index while the levels of HDL-c and GSH were found
      to be raised. Plant extract at the dose of 400 mg had a consistent effect on all
      lipid profile parameters. Lower doses (100 and 200 mg) did not produce a
      statistically significant reduction in LDL-c. In addition, the protective effect
      of C. pluricaulis was confirmed by histological analysis. Further, the findings
      of the study were found to be comparable with fenofibrate. CONCLUSIONS:
      Therefore, the present study suggests that C. pluricaulis has the potential for
      the treatment of hyperlipidaemia.

PMID- 30182366
TI  - Zinc finger protein 91 positively regulates the production of IL-1beta in
      macrophages by activation of MAPKs and non-canonical caspase-8 inflammasome.
AB  - BACKGROUND AND PURPOSE: IL-1beta is a cytokine of critical importance in
      inflammatory, infectious and autoimmune diseases. Zinc finger protein 91 (ZFP91)
      has been reported to be involved in multiple biological processes. Here, we
      identified a previously unknown role for ZFP91 in the production of biologically
      active IL-1beta and investigated the underlying mechanisms of its effects.
      EXPERIMENTAL APPROACH: In vitro, the underlying mechanisms of ZFP91 at inhibiting
      the expression of IL-1beta were investigated by ELISA, RT-PCR, Western blotting,
      immunoprecipitation and immunofluorescence assays. In vivo, colitis was induced
      by giving 4% dextran sulfate sodium (DSS) p.o. in drinking water for 5 days.
      Peritonitis was induced by injecting 700 MUg alum i.p. for 12 h. KEY RESULTS:
      ZFP91 activated the non-canonical caspase-8 inflammasome, which resulted in
      robust IL-1beta secretion. Using an immunoprecipitation assay and
      immunofluorescence assay, we found that ZFP91 promoted the assembly of the non
      canonical caspase-8 inflammasome complex. Moreover, ZFP91 enhanced the activation
      of ERK, p38 MAPK and JNK in macrophages. In addition, our data demonstrate that
      the synthesis of pro-IL-1beta is dependent on activation of these MAPK signalling
      pathways. In vivo experiments, the symptoms and colonic inflammation associated
      with DSS-induced colitis were ameliorated in mice deficient in ZFP91.
      Furthermore, the inflammation in alum-induced peritonitis was also attenuated in
      mice deficient in ZFP91. CONCLUSIONS AND IMPLICATIONS: Our research describes a
      mechanism by which ZFP91 promotes production of IL-1beta under physiological
      conditions and suggests that ZFP91 may be a promising therapeutic target for
      intervention in inflammatory, infectious and autoimmune-related diseases.

PMID- 30182367
TI  - A comparison study of the transoral and bilateral axillo-breast approaches in
      robotic thyroidectomy.
AB  - OBJECTIVES: Transoral robotic thyroidectomy (TORT) is a new remote access
      approach to avoid cervical incision. The purpose of this study is to compare two
      approaches used to avoid cervical incision: transoral approach and bilateral
      axillo-breast approach (BABA) in robotic thyroidectomy. METHODS: A total of 90
      patients were enrolled prospectively between September 2016 and April 2017. The
      BABA group had 43 and the TORT group had 47 patients, respectively. Parameters
      including clinicopathologic data, operative time, complications, laboratory data,
      hospital stay, postoperative pain, and cosmetic satisfaction were analyzed.
      RESULTS: Complications were not different among the two groups. The operative
      time of TORT was longer than BABA until 15 cases of TORT were completed, but
      there was no difference after that. The Visual Analogue Scale score in TORT was
      lower than BABA in all the periods. TORT showed a higher cosmetic satisfaction
      after surgery. There was no infection or permanent mental nerve hypoesthesia in
      TORT. CONCLUSION: Our study showed that TORT had less postoperative pain and a
      greater cosmetic satisfaction than the BABA. There were no significant
      differences in the postoperative surgical results between the two groups. TORT
      was comparable to the BABA in outcome with higher cosmetic satisfaction and less
      pain.

PMID- 30182368
TI  - In vitro gametogenesis and reproductive cloning: Can we allow one while banning
      the other?
AB  - In vitro gametogenesis (IVG) is believed to be the next big breakthrough in
      reproductive medicine. The prima facie acceptance of this possible future
      technology is notable when compared to the general prohibition on human
      reproductive cloning. After all, if safety is the main reason for not allowing
      reproductive cloning, one might expect a similar conclusion for the reproductive
      application of IVG, since both technologies hold considerable and comparable
      risks. However, safety concerns may be overcome, and are presumably not the sole
      reason why cloning is being condemned. We therefore assess the non-safety
      arguments against reproductive cloning, yet most of these can also be held
      against IVG. The few arguments that cannot be used against IVG are defective. We
      conclude from this that it will be hard to defend a ban on reproductive cloning
      while accepting the reproductive use of IVG.

PMID- 30182369
TI  - A Primary Care Ultrasound Fellowship: Training for Clinical Practice and Future
      Educators.
AB  - As ultrasound devices become smaller, more portable, and more user friendly,
      there is now widespread use of this technology by physicians of all specialties,
      yet there are currently few structured opportunities for ultrasound education
      outside of emergency and critical care medicine. Anticipating the rising
      educational demand in the primary care specialties, the University of South
      Carolina School of Medicine created a primary care ultrasound fellowship in 2011,
      the first yearlong training program in point-of-care ultrasonography for
      graduates of internal medicine, medicine-pediatrics, pediatrics, and family
      medicine residencies. This paper reviews the history of point-of-care
      ultrasonography fellowships and then provides an overview of the primary care
      ultrasound fellowship.

PMID- 30182370
TI  - Designing the blood supply chain: how much, how and where?
AB  - BACKGROUND: The topology of the blood supply chain network can take different
      forms in different settings, depending on geography, politics, costs, etc. Many
      developed countries are moving towards centralized networks. The goal for all
      blood distribution networks, regardless of topology, remains the same: to satisfy
      demand at minimal cost and minimal wastage. STUDY DESIGN AND METHODS:
      Mathematically, the blood supply system design can be viewed as a location
      allocation problem, where the aim is to find the optimal location of collection
      and production facilities and to assign hospitals to them to minimize total
      system cost. However, most location-allocation models in the blood supply chain
      literature omit several important aspects of the problem, such as selecting
      amongst differing methods of collection and production. In this paper, we present
      a location-allocation model that takes these factors into account to support
      strategic decision-making at different levels of centralization. RESULTS: Our
      approach is illustrated by a case study (Colombia) to redesign the national blood
      supply chain under a range of realistic travel time limitations. For each
      scenario, an optimal supply chain configuration is obtained, together with
      optimal collection and production strategies. We show that the total costs for
      the most centralized scenario are around 40% of the costs for the least
      centralized scenario. CONCLUSION: Centralized systems are more efficient than
      decentralized systems. However, the latter may be preferred for political or
      geographical reasons. Our model allows decision-makers to redesign the supply
      network per local circumstances and determine optimal collection and production
      strategies that minimize total costs.

PMID- 30182372
TI  - Optimal sample size allocation and go/no-go decision rules for phase II/III
      programs where several phase III trials are performed.
AB  - The conduct of phase II and III programs is costly, time-consuming and, due to
      high failure rates in late development stages, risky. There is a strong
      connection between phase II and III trials as the go/no-go decision and the
      sample size chosen for phase III are based on the results observed in phase II.
      An integrated planning of phase II and III is therefore reasonable. The success
      of phase II/III programs crucially depends on the allocation of the resources to
      phase II and III in terms of sample size and the rule applied to decide whether
      to stop or to proceed with phase III. Recently, a utility-based approach was
      proposed, where optimal planning of phase II/III programs is achieved by taking
      fixed and variable costs of the drug development program and potential gains
      after a successful launch into account. However, this method is restricted to
      programs with a single phase III trial, while regulatory authorities usually
      require statistical significance in two or more phase III trials. We present a
      generalization of this procedure to programs where two or more phase III trials
      are performed. Optimal phase II sample sizes and go/no-go decision rules are
      provided for time-to-event outcomes and cases, where at least one, two, or three
      phase III trials need to be successful. Different drug development program
      strategies (e.g. one large vs. two phase III trials) are compared within these
      different cases. Application to practical examples typically met in oncology
      trials illustrates the proposed method.

PMID- 30182371
TI  - The effect of red-blood-cell transfusion on fatigue in hospitalized patients with
      anaemia.
AB  - BACKGROUND AND OBJECTIVE: Guidelines suggest that red-blood-cell transfusion
      decisions for most hospitalized patients be based on haemoglobin (Hb)
      concentration and the presence of symptoms of anaemia, including fatigue.
      However, studies differ in whether transfusion is associated with improvements in
      fatigue. One explanation is that the benefit of transfusion varies by baseline
      fatigue levels, which existing studies have not examined. The objective of this
      study was to determine whether the association between transfusion during
      hospitalization and improvements in fatigue 30 days postdischarge varies by
      baseline fatigue level. METHODS: A prospective observational study of
      hospitalized general medicine patients with any Hb <9 g/dl. Patients with sickle
      cell anaemia and gastrointestinal bleeding were excluded since these diagnoses
      have alternative transfusion practices. Patients with depression were excluded
      because their fatigue is not primarily due to anaemia. Fatigue was measured
      during an in-person interview and a 30-day postdischarge phone interview. Hb
      values and receipt of a transfusion were collected from hospital administrative
      data. Linear regression was used to test associations between 'change in
      fatigue', Hb concentration and receipt of a transfusion. RESULTS: Transfusion
      interacted with nadir Hb was associated with reduced fatigue postdischarge for
      patients with higher baseline fatigue (20% most fatigued: beta = 12, P = 0.02;
      10% most fatigued: beta = 17, P = 0.02). Patients <50 years old with high
      baseline fatigue had large reductions in fatigue from transfusion (20%: beta =
      23, P = 0.02; 10%: beta = 29, P = 0.03). CONCLUSIONS: Transfusion during
      hospitalization is associated with reduced fatigue 30 days postdischarge in
      patients with higher levels of baseline fatigue.

PMID- 30182373
TI  - EGCG inhibits CSC-like properties through targeting miR-485/CD44 axis in A549
      cisplatin resistant cells.
AB  - Non-small cell lung cancer (NSCLC) remains one of the most aggressive tumors with
      low life expectancy worldwide. The existence of cancer stem cells (CSCs)
      contributes to the failure of cancer treatment resulted from drug resistance.
      Altered microRNA expression has been observed in human tumors due to its role in
      tumor growth, progression, and metastasis. Hence, the aim of our present study
      was to investigate the effects of miR-485 on the CSC-like traits in NSCLC A549
      cisplatin resistant cells and concentrate on the underlying molecular mechanism.
      It was found that CSC-like phenotypes were much more enriched in A549/cisplatin
      (A549/CDDP) cells compared to A549-parental cells. In addition, we observed that
      miR-485 was greatly decreased in A549/CDDP cells and miR-485 overexpression was
      able to decrease the stemness of A549/DDP cells. Meanwhile, epigallocatechin-3
      gallate (EGCG), a green tea polyphenol which has been identified as an effective
      anticancer compound was able to increase miR-485 expression dose-dependently in
      A549/CDDP cells. Inhibitors of miR-485 remarkably increased CSC-like phenotypes,
      which could be reversed by indicated doses of EGCG. Moreover, CD44 was predicted
      as downstream target of miR-485 and the correlation between them was validated by
      performing dual-luciferase reporter assay and RNA immunoprecipitation (RIP)
      assay. Subsequently, in vivo experiments were employed to confirm that EGCG
      restrained CSC-like characteristics by increasing miR-485 and decreasing CD44
      expression. Taken together, it was implied that stemness features and CSC
      population were suppressed by EGCG-modulated miR-485/CD44 axis in A549/CDDP
      cells.

PMID- 30182374
TI  - Cobalt-Pincer Complexes in Catalysis.
AB  - Non-noble metal catalysts based on pincer type compounds are of special interest
      for organometallic chemistry and organic synthesis. Next to iron and manganese,
      currently cobalt-pincer type complexes are successfully applied in various
      catalytic reactions. In this review the recent progress in (de)hydrogenation,
      transfer hydrogenation, hydroboration and hydrosilylation as well as
      dehydrogenative coupling reactions using cobalt-pincer complexes is summarised.

PMID- 30182375
TI  - Resolving the paradox of clumped seed dispersal: positive density and distance
      dependence in a bat-dispersed species.
AB  - One of the hypothesized benefits of seed dispersal is to escape density- and
      distance-responsive, host-specific, natural enemies near maternal plants where
      conspecific seed and seedling densities are high. Such high conspecific neighbor
      densities typically result in lower offspring growth and survival (i.e., negative
      density-dependent effects), yet many dispersal modes result in clumped seed
      distributions. New World leaf-nosed bats transport fruits to their feeding roosts
      and deposit seeds, thereby creating high-density seed/seedling patches beneath
      feeding roosts in heterospecific trees away from maternal trees, which seemingly
      nullifies a key benefit of seed dispersal. Such dispersal may still be adaptive
      if negative density-dependent effects are reduced under feeding roosts or if the
      benefit of being dispersed away from maternal trees outweighs negative effects of
      conspecific seed/seedling density below roosts. We mapped the entire post
      germination population of a bat-dispersed tree species Calophyllum longifolium
      (Calophyllaceae) in a 50-ha plot on Barro Colorado Island, Panama in each of
      three successive years. We tested two hypotheses: (1) distance-dependent effects
      are stronger than density-dependent effects on seedling performance because
      seedlings far from conspecific adults are more likely to escape natural enemies
      even when at high densities and (2) negative density-dependent effects will be
      reduced far from vs. near conspecific adults. Density and distance were naturally
      decoupled, as expected. However, in contrast to our expectation, we found
      positive density effects on seedling survival and density-dependent effects did
      not differ with distance from conspecific adults. Both density and distance had
      positive effects on seedling survival when considered together, while only year
      had a significant effect on seedling growth. Thus, both being dispersed under bat
      feeding roosts and escaping the vicinity of conspecific adults were beneficial
      for C. longifolium seedling survival, supporting the directed dispersal and
      escape hypotheses, respectively. Despite resulting in high densities of
      conspecific seedlings, favorable habitat under bat feeding roosts and lack of
      negative density-dependent effects appear to provide evolutionary advantages in
      C. longifolium.

PMID- 30182376
TI  - The impact of a primary health care intervention on infant feeding practices: a
      cluster randomised controlled trial in Brazil.
AB  - BACKGROUND: Proper feeding practices in early life can enhance the full human
      potential development of children. We aimed to evaluate the impact of a primary
      health care intervention on infant feeding practices among children from low
      income families. METHODS: A cluster randomised controlled trial was conducted in
      Porto Alegre, Brazil. Healthcare centres were randomised into intervention (n =
      9) and control (n = 11) groups. In intervention sites, health workers were
      trained in accordance with the national guidelines. Infant feeding practices were
      assessed in children at 6 months (n = 617) and 12 months (n = 516) of age.
      Feeding practice quality was assessed using the Infant and Child Feeding Index
      (ICFI). Additionally, we evaluated the introduction of nonrecommended foods.
      RESULTS: At 6 months, the mean ICFI score was higher in the intervention group
      [MD = 0.22; 95% confidence interval (CI) = 0.24-1.11]. The prevalence of infants
      who met the recommendation for meat into the food-frequency score was higher in
      the intervention than the control group [relative risk (RR) = 1.63; 95% CI = 1.26
      2.11]. At 12 months of age, the ICFI mean (MD = 0.23; 95% CI = 0.35-0.56) and the
      prevalence of children who met the recommendation for dietary diversity (RR =
      1.11; 95% CI = 1.01-1.22) and meal frequency (RR = 4.68; 95% CI = 1.34-16.36)
      were higher in the intervention group, although only among children who had more
      than seven follow-up appointments during the first year of life. The children
      from intervention group had a significant delay for added sugar (MD = 0.51; 95%
      CI = 0.13-0.89), tea (mean = 0.47; 95% CI = 0.13-0.82), jelly (MD = 0.35; 95% CI
      = 0.11-0.58) and filled cookies (MD = 0.29; 95% CI = 0.06-0.52) compared to the
      control group. CONCLUSIONS: The health workers' training was effective with
      respect to improving infant feeding practices.

PMID- 30182377
TI  - miR-365 regulates liver cancer stem cells via RAC1 pathway.
AB  - Liver cancer stem cells (CSCs) were involved in tumorigenesis, progression,
      recurrence, and drug resistance of hepatocellular carcinoma (HCC). miR-365 was
      downregulated in hepatocellular carcinoma and inhibited HCC cell proliferation
      and invasion. However, the role of miR-365 in liver cancer stem cells was
      unknown. Herein, we observed a remarkable decrease of miR-365 expression in CD133
      or EpCAM-positive liver CSCs as well as in CSC-enriched hepatoma spheres. Up
      regulated miR-365 suppressed liver CSC expansion by inhibiting the
      dedifferentiation of hepatoma cells and decreasing the self-renewal ability of
      liver CSCs. Mechanistically, bioinformatic and luciferase reporter analysis
      identified Ras-related C3 botulinum toxin substrate 1 (RAC1) as a direct target
      of miR-365. Overexpression of miR-365 in hepatoma cells downregulated the RAC1
      mRNA and protein expression. RAC1 also could promote the expansion of liver CSCs.
      The special RAC1 inhibitor EHop-106 or RAC1 overexpression abolished the
      discrepancy in liver CSC proportion and the self-renewal capacity between miR-365
      overexpression hepatoma cells and control cells, which further confirmed that
      RAC1 was required in miR-365-suppressed liver CSCs expansion. miR-365 was
      downregulated in liver CSCs and could inhibit HCC cells dedifferentiation and
      liver CSCs expansion by targeting RAC1 signaling.

PMID- 30182378
TI  - HUS1 checkpoint clamp component (HUS1) is a potential tumor suppressor in primary
      hepatocellular carcinoma.
AB  - The HUS1 checkpoint clamp component (HUS1), which is a member of an
      evolutionarily conserved, genotoxin-activated checkpoint complex (Rad9-Rad1-Hus1
      [9-1-1] complex), is involved in cell cycle arrest and DNA repair in response to
      DNA damage. We conducted this study to investigate the biological significances
      of HUS1 expression in hepatocellular carcinoma (HCC) development. The mRNA and
      protein expression levels of HUS1 were determined using Real-time PCR and Western
      blot, respectively. One hundered and twenty four paraffin sections from HCC
      tissues were analyzed by immunohistochemistry to assess the association between
      HUS1 expression and clinicopathological characteristics of patients. The Kaplan
      Meier method was performed to calculate the OS and RFS curves. Cell proliferation
      and colony formation assays, cell migration and invasion assays and cell cycle
      assays were used to determine the suppressor role of HUS1 in vitro. A mouse model
      was used to determine the effect of HUS1 on tumorigenesis. The expression of HUS1
      was significantly decreased in HCC cell lines and tissues, and low HUS1
      expression was associated with poor prognosis of HCC patients. Upregulation of
      HUS1 expression inhibited the cell proliferation, colony formation, migration,
      and invasion, as well as arrested cell cycle at G0/G1 in HCC cells in vitro.
      Moreover, sufficient HUS1 expression inhibited the tumor growth in nude mice. Our
      study revealed for the first time that HUS1 is a potential tumor suppressor that
      might produce an antitumor effect in human HCC. Furthermore, HUS1 may serve as a
      prognostic indicator and could be used for therapeutic application in HCC
      patients.

PMID- 30182379
TI  - Equivalence class formation as a function of preliminary training with pictorial
      stimuli.
AB  - The present experiment investigated the effects of preliminary training with
      pictorial stimuli on the subsequent formation of three 5-member equivalence
      classes (A?B?C?D?E) in 84 university students assigned to seven groups of 12. In
      the Abstract (ABS) group, all stimuli were abstract shapes. In the Picture (PIC)
      group, the C stimuli were pictures, and the remaining stimuli were the same
      abstract shapes as in the ABS group. For the remaining five groups, all stimuli
      were the same abstract shapes as in the ABS group. However, across groups,
      preliminary training involved either the establishment of conditional relations
      with simultaneous (SMTS) or delayed (DMTS) matching-to-sample with 0 s, 3 s, 6 s,
      or 9 s between the abstract C stimuli and the meaningful pictures. For the ABS
      and the PIC groups, 16.7% and 83.3% of participants formed classes, respectively.
      Preliminary training with SMTS and DMTS with 0 s, 3 s, and 6 s produced a linear
      increase in the likelihood of equivalence class formation, 41.7%, 50%, and 75%,
      respectively. Increasing the duration of delay further from 6 s to 9 s produced a
      substantial decline, 50%. This experiment extends knowledge about how including
      meaningful pictures enhances equivalence class formation.

PMID- 30182380
TI  - Rumen responses to dietary supplementation with cashew nut shell liquid and its
      cessation in sheep.
AB  - Rumen responses to cashew nut shell liquid (CNSL) were evaluated in a feeding
      study. Four wethers were fed a hay and concentrate diet for 4 weeks (pre-CNSL
      period), and then fed the same diet supplemented with low and high levels of CNSL
      for 2 weeks each (L-CNSL and H-CNSL periods respectively). The diet was then
      reverted to the unsupplemented control diet for another 2 weeks (post-CNSL
      period). Rumen parameters were monitored in each feeding period. CNSL, regardless
      of the two levels tested, did not show any adverse effects on total short chain
      fatty acid concentration and dry matter digestibility in the rumen. Propionate
      proportion increased in the H-CNSL period, while methane production potential,
      acetate and butyrate proportions, viscosity, foam formation and its stability,
      and ammonia concentration decreased. Values of these parameters returned to those
      in the unsupplemented control period after cessation of CNSL supplementation.
      Clone library analysis of 16S rRNA genes revealed the following shifts in the H
      CNSL period. For bacteria, Firmicutes was frequently detected, while
      Bacteroidetes and Spirochetes were not. For archaea, Methanobrevibacter wolinii
      was predominant. These results indicate that CNSL could be a methane inhibitor
      and propionate enhancer by altering the rumen microbial community.

PMID- 30182381
TI  - CDR1as is overexpressed in laryngeal squamous cell carcinoma to promote the
      tumour's progression via miR-7 signals.
AB  - OBJECTIVES: To investigate the roles played by the circular RNA (circRNA)
      molecule ciRS-7 (CDR1as) and tumour suppressor miRNA-7 (miR-7) in laryngeal
      squamous cell carcinoma (LSCC). METHODS: Specimens of LSCC tissue (n = 30) and
      corresponding relative normal tissue (n = 30) were collected to determine their
      levels and clinical significance of CDR1as/mir-7 expression. The CDR1as and miR-7
      were overexpressed in LSCC cells to investigate its function and mechanism in
      vitro and in vivo. RESULTS: Patients with high TNM stages, poorly differentiated
      tumours, lymph node metastases and poor prognosis had high CDR1as levels but low
      miR-7 levels. CDR1 expression was negatively associated with miR-7 expression in
      LSCC. Overexpression of CDR1as in vitro enhanced cell vitality, and promoted the
      proliferation, migration, and invasion of two LSCC cell lines (Hep2 and AMC-HN
      8.) However, these effects could be abrogated by knockdown of CDR1as or the
      forced expression of miR-7. Mechanistically, overexpressed CDR1 molecules
      functioned as miR-7 sponges and upregulated the key targets of miR-7, CCNE1, and
      PIK3CD in Hep2 and AMC-HN-8 cells. In vivo studies demonstrated the tumourigenic
      role of CDR1as. Overexpression of CDR1as alone promoted tumour growth and
      increased expression of the proliferation indices ki-67, CCNE1, and PIK3CD.
      Although the tumour suppressor miR-7 effectively inhibited the tumour growth,
      this effect could be counteracted by co-treatment with CDR1as in vivo.
      CONCLUSION: CDR1as is an oncogene that promotes LSCC progression by regulating
      miR-7 signals.

PMID- 30182382
TI  - Biomedical Applications of Fluorescent and Magnetic Resonance Imaging Dual
      Modality Probes.
AB  - Molecular imaging plays a critical role in biomedical research. The combination
      of different modalities can generate complementary information and provide
      synergistic advantages over single modality alone. Noninvasive and nonradioactive
      fluorescent imaging (FI)/magnetic resonance imaging (MRI) dualmodality probes
      fuse the high sensitivity of FI and the high temporal and spatial resolution and
      deep-tissue penetration of MRI, and their increasing applications have been
      reported in biomedical research and clinical practices, including cell labeling,
      enzyme activity measurement, tumor diagnosis and therapy, and anatomical
      localization and real-time assessment during surgery.

PMID- 30182383
TI  - Nursing workload and compliance with non-pharmacological measures to prevent
      ventilator-associated pneumonia: a multicentre study.
AB  - BACKGROUND: Ventilator-associated pneumonia is common and associated with high
      mortality. Nurses play a fundamental role in preventing ventilator-associated
      pneumonia. Evidence-based guidelines and training interventions about preventing
      ventilator-associated pneumonia do not ensure compliance with recommendations.
      AIMS AND OBJECTIVE: To evaluate the impact of nursing workload on compliance with
      non-pharmacological measures to prevent ventilator-associated pneumonia. DESIGN:
      A prospective observational study in two medical-surgical adult ICUs in Spain.
      METHODS: We measured nurses' knowledge about preventing ventilator-associated
      pneumonia through a questionnaire and workload, categorized with the Nine
      Equivalents of Nursing Manpower Use Score. We directly observed nurses to measure
      compliance with non-pharmacological measures to prevent ventilator-associated
      pneumonia. RESULTS: A total of 97 nurses were studied; 76 (79%) were observed.
      There were 327 observations (mean 4.30 observations per nurse). The questionnaire
      showed good baseline knowledge of preventive measures [mean score (92% +/- 16%)].
      Nurses complied with the preventive measures in 66% +/- 15% of observations;
      compliance ranged from 11.9% for pre-aspiration hand washing to 99.7% for using
      sterile aspiration probes. Mean Nine Equivalents of Nursing Manpower Use Score
      for each nurse observed was 50 +/- 13, without differences between centres (49 +/
      14 versus 51 +/- 11, p = 0.4). Overall compliance was lower in the light
      workload group (p = 0.02), but no significant differences in compliance between
      workload groups were found when each measure was analysed separately. Compliance
      was higher in nurses aged 31-40 years than in those aged >51 years, although
      workload was similar in both groups. CONCLUSIONS: Compliance with non
      pharmacological measures to prevent ventilator-associated pneumonia varies
      widely; non-compliance is not because of increased workload. RELEVANCE TO
      CLINICAL PRACTICE: Most critical care nurses have good baseline knowledge of non
      pharmacological measures to prevent ventilator-associated pneumonia. Failure to
      comply with these measures is probably more related with behavioural, structural
      and organizational aspects than with nursing workload. Interventions to improve
      compliance might be more effective if they focus on factors such as work climate
      and professionals' attitudes.

PMID- 30182385
TI  - Corrigendum.

PMID- 30182384
TI  - Integrative functional genomics identifies regulatory genetic variant modulating
      RAB31 expression and altering susceptibility to breast cancer.
AB  - Despite the successes of genome-wide association study (GWAS) in identifying
      breast cancer (BC) risk-associated variants, only a small fraction of the
      heritability can be explained. The greatest challenge in the post-GWAS is to
      identify causal variants and underlying mechanisms responsible for BC
      susceptibility. In this study, we integrated functional genomic data from ENCODE
      ChIP-seq, ANNOVAR, and the TRANSFAC matrix to identify potentially regulatory
      variants with modulating FOXA1-binding affinity across the whole genome, and then
      conducted a two-stage case-control study including 2164 cases and 2382 controls
      to investigate the associations between candidate SNPs and BC susceptibility. We
      identified a BC susceptibility SNP, rs6506689 G>T, with an odds ratio (OR) of
      1.23 (95% confidence interval = 1.07-1.40, P = 0.003) under a dominant model in
      the combined study. Biological assays indicated that the germline G>T variation
      at rs6506689 creates a FOXA1-binding site and up-regulates the expression of
      RAB31, thus playing an important role in the development of BC. Our results
      highlight the importance of regulatory genetic variants in the development of BC
      by influencing TF-DNA interaction and provide critical insights to pinpoint
      causal genetic variants.

PMID- 30182386
TI  - Peri-implant inflammation and marginal bone level changes around dental implants
      in relation to proximity with and bone level of adjacent teeth.
AB  - OBJECTIVES: This retrospective study assessed radiographic bone changes and
      prevalence of inflammation around teeth and neighbouring implants supporting a
      single-unit fixed dental prosthesis (FDP), in relation to implant- positioning
      and characteristics. MATERIAL AND METHODS: Patients with an implant-supported FDP
      in function for at least 1 year were recruited. The radiographic horizontal and
      vertical position of the implants were identified. Probing depth (PD), bleeding
      on probing (BOP) and radiographic bone level around implants and adjacent teeth
      at the time of placement, prosthesis delivery, and the most recent review were
      assessed. RESULTS: 98 patients with 195 implants were evaluated for a mean of
      37.8 months. Survival rate was 99.6% and success ranged from 31.3% to 91.3% when
      different success criteria were utilized. Significantly greater interproximal
      bone loss around teeth and higher prevalence of interproximal peri-implant
      inflammation occurred when the horizontal distance of BL implants was <1 mm, but
      not with TL implants. There was no significant impact of the corono-apical
      positioning of the implants on marginal bone loss. CONCLUSION: Proximity of
      implants to adjacent teeth of <1 mm leads to increased prevalence of inflammation
      and interproximal bone resorption at the teeth adjacent to bone level implants.

PMID- 30182387
TI  - Altered excitability and exocytosis in chromaffin cells from the R6/1 mouse model
      of Huntington's disease is linked to over-expression of mutated huntingtin.
AB  - As the peripheral sympathoadrenal axis is tightly controlled by the cortex via
      hypothalamus and brain stem, the central pathological features of Hunting's
      disease, (HD) that is, deposition of mutated huntingtin and synaptic
      dysfunctions, could also be expressed in adrenal chromaffin cells. To test this
      hypothesis we here present a thorough investigation on the pathological and
      functional changes undergone by chromaffin cells (CCs) from 2-month (2 m) to 7
      month (7 m) aged wild-type (WT) and R6/1 mouse model of Huntington's disease
      (HD), stimulated with acetylcholine (ACh) or high [K+ ] (K+ ). In order to do
      this, we used different techniques such as inmunohistochemistry, patch-clamp, and
      amperometric recording. With respect to WT cells, some of the changes next
      summarized were already observed in HD mice at a pre-disease stage (2 m);
      however, they were more pronounced at 7 m when motor deficits were clearly
      established, as follows: (i) huntingtin over-expression as nuclear aggregates in
      CCs; (ii) smaller CC size with decreased dopamine beta-hydroxylase expression,
      indicating lesser number of chromaffin secretory vesicles; (iii) reduced adrenal
      tissue catecholamine content; (iv) reduced Na+ currents with (v) membrane
      hyperpolarization and reduced ACh-evoked action potentials; (v) reduced [Ca2+ ]c
      transients with faster Ca2+ clearance; (vi) diminished quantal secretion with
      smaller vesicle quantal size; (vii) faster kinetics of the exocytotic fusion
      pore, pore expansion, and closure. On the basis of these data, the hypothesis is
      here raised in the sense that nuclear deposition of mutated huntingtin in adrenal
      CCs of R6/1 mice could be primarily responsible for poorer Na+ channel expression
      and function, giving rise to profound depression of cell excitability, altered
      Ca2+ handling and exocytosis. OPEN PRACTICES: This article has received a badge
      for *Open Materials* because it provided all relevant information to reproduce
      the study in the manuscript. The complete Open Science Disclosure form for this
      article can be found at the end of the article. More information about the Open
      Practices badges can be found at https://cos.io/our-services/open-science
      badges/. Cover Image for this issue: doi: 10.1111/jnc.14201.

PMID- 30182388
TI  - Bridging health access disparities among culturally and linguistically diverse
      cancer patients: an ongoing challenge.

PMID- 30182389
TI  - Association of obstructive sleep apnoea with acute severity of chronic
      obstructive pulmonary disease exacerbation: a population-based study.
AB  - Little is known about the association of obstructive sleep apnoea (OSA) with the
      severity of acute exacerbation of chronic obstructive pulmonary disease (AECOPD).
      This retrospective cohort study investigated the association of coexistent OSA
      with acute severity markers (i.e. invasive positive pressure ventilation (IPPV)
      use and hospital length of stay (LOS)) among adults hospitalised for AECOPD.
      Patients with coexistent OSA had a significantly higher risk of IPPV use and
      prolonged hospital LOS compared to those without OSA.

PMID- 30182390
TI  - Occipital condyle syndrome mimicking giant cell arteritis as the first
      manifestation of disseminated malignancy.

PMID- 30182391
TI  - Phosphate nephropathy: an avoidable complication of bowel preparation for
      colonoscopy.
AB  - It is known that oral sodium phosphate, used as bowel preparation for
      colonoscopy, can cause acute phosphate nephropathy, a potentially severe and
      irreversible form of acute kidney injury. Due to these safety concerns,
      guidelines have advised against the routine use of this agent for a decade. We
      present a case report and biopsy series that demonstrate that oral sodium
      phosphate is still being used and that cases of APN are still occurring, in
      Australia.

PMID- 30182392
TI  - Australian driving restrictions: how well do neurologists know them?
AB  - Driving regulations are complex, particularly for neurological conditions, but
      accurate application of restrictions is important. This study was designed to
      investigate knowledge of the Austroads guidelines in medical students,
      neurological trainees and consultant neurologists using a questionnaire
      addressing both private and commercial licence restrictions related to five
      common neurological conditions, namely transient ischaemic attack (TIA),
      vasovagal episode, unwitnessed blackout, first epileptic seizure and benign
      paroxysmal positional vertigo. In total, 118 of the 120 returned responses could
      be analysed. Overall, 50% of all responses were correct. Respondents performed
      better for private than commercial licences, and consultants performed better
      than trainees and students. The highest proportion of correct answers was seen
      for vasovagal attack, and the lowest for TIA. In summary, knowledge of driving
      restrictions was relatively poor, and regular consultation of the guidelines is
      recommended. A larger study is warranted and increased education at both medical
      school and postgraduate levels should be considered.

PMID- 30182393
TI  - Variation in the incidence and timing of diagnosis of hospital-associated venous
      thromboembolism using linked administrative data.
AB  - Venous thromboembolism (VTE) is a potentially preventable adverse effect of
      hospitalisation. Inter-hospital variation in the incidence of hospital-associated
      VTE (HA-VTE) and timing of diagnosis (in-hospital or post-discharge) in New South
      Wales public hospitals were examined. Large variations in incidence (22% risk
      difference) and post-discharge diagnosis (115% odds difference) were evident
      after adjustment for case mix, which only explained 59% and 32% of inter-hospital
      variation respectively. The need for improved compliance with best practice
      guidelines is reinforced.

PMID- 30182394
TI  - A review of the hours dedicated to oral health education in medical programmes
      across Australia.
AB  - BACKGROUND: Oral health is an important predictor for general health, and poor
      oral health is interrelated with the manifestations of systemic disease. AIM: To
      determine the extent of oral health education in medical schools across
      Australia. METHODS: A survey of Australian medical schools was conducted
      (September 2013 to June 2014). Participants were administrators and curricula
      coordinators of medical programmes. The main outcome measures were teaching hours
      of specific areas of oral health education. Data were descriptively analysed.
      RESULTS: Participants from 8 of 18 universities responded to the questionnaire.
      The total hours dedicated to oral health in the medical programmes were: zero in
      one school; less than 2 h in three schools, 6-10 h in three schools and 30 h in
      one school. Only four schools taught the correlation between oral health and
      overall health, two schools taught about dental diseases (caries and periodontal
      disease), three schools taught dental trauma management and six schools taught
      oral anatomy. Only five schools taught about oral cancer: two of these taught
      about cancer for 10-15 min. No school reported hands-on training in an oral
      health setting. CONCLUSIONS: The results indicate that Australian medical school
      graduates have little, if any, foundational knowledge of oral health (dental
      caries, bidirectional relationship between diabetes and periodontal disease, oral
      cancer and dental emergencies). The recognition of poor oral health plays a
      significant part in the early detection and care of chronic diseases. The
      teaching of fundamental oral health to medical students is crucial and should be
      integrated into medical school curricula.

PMID- 30182395
TI  - What if I cannot choose wisely? Addressing suboptimal health literacy in our
      patients to reduce over-diagnosis and overtreatment.
AB  - The Choosing Wisely initiative aims to reduce wasteful and harmful healthcare by
      encouraging clinicians and patients to discuss explicitly the healthcare that is
      really needed as well as that which is of low or no value. While low health
      literacy has been found to be associated with under-diagnosis and under
      treatment, its potential role as a driver of over-diagnosis and overtreatment has
      received less attention. This article describes how low health literacy might
      lead to too much medicine. It then provides an overview of an evidence-based
      method of communication that might assist with identifying and addressing low
      health literacy in patients.

PMID- 30182396
TI  - Sustained ventricular tachycardia caused by subacute thyroiditis.

PMID- 30182397
TI  - Left atrial myxoma presenting as foot pain.

PMID- 30182398
TI  - Optimal cancer drug dosing in adolescents: new issues and the old unaddressed
      ones.

PMID- 30182399
TI  - Fournier gangrene: an historical reappraisal.
AB  - Perineal gangrene (synergistic gangrene), an age-old severe infectious disorder,
      was more completely described by Dr Robert Robertson (1742-1829) in 1777,
      providing much needed data on the clinical features well before Dr Jean Alfred
      Fournier's (1832-1914) account in 1883. Robertson's historically overlooked and
      detailed narrative is presented with implications, in part, refuting some
      conclusions made by Fournier 100 years later.

PMID- 30182400
TI  - Clinical utility of (99m Tc)-TRODAT-1 scans to differentiate Parkinsonian
      syndromes: case studies and commentary.
AB  - The differential diagnosis of Parkinsonian syndromes is challenging, especially
      in the elderly as they often have complex presentations. Nuclear imaging
      modalities can increase diagnostic accuracy. Single-photon emission tomography
      (SPECT) using the ligand (99m Tc)-TRODAT-1 is used overseas but is yet to be
      approved in Australia. Three pilot cases of clinically unclear Parkinsonian
      syndromes from the Royal North Shore Hospital Aged Care Department who underwent
      (99m Tc)-TRODAT-1 scans are described. From experience overseas, the (99m Tc)
      TRODAT-1 scan has clinical utility in the differential diagnosis of Parkinsonian
      syndromes. (99m Tc)-TRODAT-1 has a lower cost and greater availability than other
      ligands. Our initial scan findings are largely consistent with the clinical
      picture, but low specific binding can affect scan interpretation. (99m Tc)-TRODAT
      1 is a potential tool in the differential diagnosis of Parkinsonian syndromes.
      Further experience regarding its effect on patient outcomes and cost
      effectiveness is required before routine clinical use can be recommended.

PMID- 30182401
TI  - Tudor knockdown disrupts ovary development in Bactrocera dorsalis.
AB  - One of the main functions of the piwi-interacting RNA pathway is the post
      transcriptional silencing of transposable elements in the germline of many
      species. In insects, proteins belonging to the Tudor superfamily proteins
      belonging to the Tudor superfamily play an important role in to play an important
      role in this mechanism. In this study, we identified the tudor gene in the
      oriental fruit fly, Bactrocera dorsalis, investigated the spatiotemporal
      expressional profile of the gene, and performed a functional analysis using RNA
      interference. We identified one transcript for a tudor homologue in the B.
      dorsalis transcriptome, which encodes a protein containing the typical 10 Tudor
      domains and an Adenosine triphosphate (ATP) synthase delta subunit signature.
      Phylogenetic analysis confirmed the identity of this transcript as a tudor
      homologue in this species. The expression profile indicated a much higher
      expression in the adult and pupal stages compared to the larval stages (up to a
      60-fold increase), and that the gene was mostly expressed in the ovaries,
      Malpighian tubules and fat body. Finally, gene knockdown of tudor in B. dorsalis
      led to clearly underdeveloped ovaries in the female adult and reductions in
      copulation rate and amount of oviposition, indicating its important role in
      reproduction. The results of this study shed more light on the role of tudor in
      ovary development and reproduction.

PMID- 30182402
TI  - Artifacts in 3D rendering: secondary palate concealed in acoustic shadow and use
      of edge-detection filters.

PMID- 30182403
TI  - Re: Cerebroplacental ratio thresholds measured within 2 weeks before birth and
      risk of Cesarean section for intrapartum fetal compromise and adverse neonatal
      outcome. L. N. Bligh, A. A. Alsolai, R. M. Greer and S. Kumar. Ultrasound Obstet
      Gynecol 2018; 52: 340-346.

PMID- 30182404
TI  - Reply.

PMID- 30182405
TI  - Re: Maternal hemodynamics in normal pregnancy and in pregnancy affected by pre
      eclampsia. D. Stott, O. Nzelu, K. H.Nicolaides and N. A. Kametas. Ultrasound
      Obstet Gynecol 2018; 52: 359-364.

PMID- 30182406
TI  - Smoking and the surgeon: no more excuses.

PMID- 30182407
TI  - Re: Transanal endoscopic microsurgery: a New Zealand experience.

PMID- 30182408
TI  - Re: Neutrophil-to-lymphocyte ratio predicts anastomotic dehiscence.

PMID- 30182409
TI  - Correspondence from specialist surgical outpatient clinics to general
      practitioners.

PMID- 30182410
TI  - Response to Re: Neutrophil-to-lymphocyte ratio predicts anastomotic dehiscence.

PMID- 30182411
TI  - Legacy of Le Quesne: operative cholangiography in the modern era.

PMID- 30182412
TI  - Acute presentation of post-operative kwashiorkor and refeeding syndrome
      complicated by chronic Strongyloides infection in an elderly patient.

PMID- 30182413
TI  - Doctor-doctor: the impact of early career higher degrees in surgical research.

PMID- 30182414
TI  - Corrigendum.

PMID- 30182415
TI  - Response to Re: Transanal endoscopic microsurgery: a New Zealand experience.

PMID- 30182416
TI  - 'To a man with a hammer, everything looks like a nail' (Abraham Maslow).

PMID- 30182417
TI  - 25, 50 & 75 years ago.

PMID- 30182418
TI  - Lack of response to quinidine in KCNT1-related neonatal epilepsy.
AB  - OBJECTIVE: To evaluate the clinical efficacy and safety of quinidine in patients
      with KCNT1-related epilepsy of infancy with migrating focal seizures (EIMFS) in
      the infantile period and to compare with the effect of quinidine on mutant
      channels in vitro. METHODS: We identified 4 patients with EIMFS with onset in the
      neonatal period, pathogenic variants in the KCNT1 gene, and lack of response to
      AEDs. Patients were prospectively enrolled, treated with quinidine, and monitored
      according to a predefined protocol. Electroclinical, neuroimaging, and genetic
      data were reviewed. Two patients had novel variants in the KCNT1 gene that were
      modeled in Xenopus oocytes with channel properties characterized using
      electrophysiology recordings. RESULTS: Three of four patients were treated with
      quinidine early in their disease course, prior to 6 months of age. No significant
      side effects were noted with quinidine therapy. In addition, there were no
      significant changes in electroencephalography (EEG)-confirmed seizure burden
      during therapy, and patients had near hourly seizures before, during, and after
      treatment. Two patients had previously reported gain-of-function mutations, which
      demonstrated sensitivity to high levels of quinidine in the oocyte assay. Two
      patients with novel variants, showed characteristic gain-of-function and were
      thus predicted to be pathogenic. Of interest, these variants were essentially
      insensitive to high levels of quinidine. SIGNIFICANCE: Patients had no reported
      benefit to quinidine therapy despite age at treatment initiation. Pharmacogenetic
      results in oocytes were consistent with clinical treatment failure in 2 patients,
      suggesting that single-dose pharmacologic assessment may be helpful in predicting
      which patients are exceedingly unlikely to achieve benefit with quinidine. In the
      2 patients who had a lack of therapeutic benefit despite sensitivity to high
      concentrations of quinidine with in vitro oocyte assay, it is likely that the
      achievable exposure levels in the brain were too low to cause significant in vivo
      channel blockade.

PMID- 30182419
TI  - Active Sites on Nickel-Promoted Transition-Metal Sulfides That Catalyze
      Hydrogenation of Aromatic Compounds.
AB  - Hydrogenation on Mo and W sulfides occurs at the edges of the sulfide slabs. The
      rate of hydrogen addition is directly proportional to the concentration of
      sulfhydryl (SH) groups at the slab edge and the metal atom attached to it.
      Sulfhydryl groups vicinal to edge-incorporated Ni hydrogenate with much higher
      rates than SH close to Mo and W. Each subset of SH groups, however, exhibits
      nearly identical intrinsic activity and selectivity, independent of the sulfide
      composition. The higher activity of Ni-WS2 compared to Ni-MoS2 stems from a
      higher concentration of SH groups on the former sulfide associated with a higher
      tendency of its surface vacancies to react with H2 .

PMID- 30182420
TI  - Constructing a grounded theory of critical illness survivorship: The dualistic
      worlds of survivors and family members.
AB  - AIM OF THE STUDY: To understand the critical illness trajectory from patient and
      relative perspectives. BACKGROUND: In the context of increasing survivorship from
      critical illness, it is important to enhance our understanding of the subjective
      experience of survivors and their families. The need to consider the legacy of
      critical care beyond physiological survival is imperative. METHODS: Using a
      constructivist grounded theory methodology, in-depth interviews were undertaken
      with survivors of critical illness (n = 16) and family members (n = 15). Constant
      comparative analysis and data collection occurring concurrently with theoretical
      sampling commencing from the outset. EQUATOR guidelines for qualitative research
      (COREQ) applied. FINDINGS: Survivors of critical illness invariably experienced
      vivid, hallucinatory experiences which placed them in a different world or
      liminal space. The core difficulty can be summarised as follows: Survivors have
      little recall of the factual events of their critical illness but relatives have
      lived the whole event in a very real and ingraining manner. This can result in
      family members and survivors experiencing different versions of the critical
      illness episode. CONCLUSION: Survivors of critical illness, together with family
      members, experience challenges when endeavouring to readjust to life post
      critical care. This study has identified a middle range theory of dualistic
      worlds between and within the survivor and family member experiences. Exploring
      the dynamic interplay between intrapersonal, interpersonal and societal factors
      has provided theoretical insights with practice implications in relation to
      surviving critical illness. RELEVANCE TO CLINICAL PRACTICE: The findings from
      this study highlight the need for a rehabilitation infrastructure following
      critical illness to support the existing UK national guidance, ensuring the
      individual and holistic needs of survivors and their families are met.
      Conversations with survivors and their families around critical illness
      survivorship are frequently absent and needed early in the recovery period.

PMID- 30182422
TI  - RANZCOG 2018 Annual Scientific Meeting "Shifting Sands: Exploring the Boundaries
      of Specialisation", 16-19 September 2018, Adelaide Convention Centre, Adelaide,
      South Australia.

PMID- 30182421
TI  - Analysis of the structural and mechanical effects of procoagulant agents on
      neonatal fibrin networks following cardiopulmonary bypass.
AB  - Essentials The standard of care (SOC) for treating neonatal bleeding is
      transfusion of adult blood products. We compared neonatal clots formed with
      cryoprecipitate (SOC) to two procoagulant therapies. The current SOC resulted in
      clots with increased stiffness and decreased fibrinolytic properties.
      Procoagulant therapies may be a viable alternative to SOC treatment for neonatal
      bleeding. SUMMARY: Background Bleeding is a serious complication of neonates
      undergoing cardiopulmonary bypass (CPB) and associated with substantial morbidity
      and mortality. Bleeding is addressed through the transfusion of adult blood
      products, including platelets and cryoprecipitate. However, significant
      differences exist between neonatal and adult clotting components, specifically
      fibrinogen. Our recent ex vivo studies have shown that neonatal fibrinogen does
      not fully integrate with adult fibrinogen, leading to decreased susceptibility to
      fibrinolysis. These differences may contribute to ineffective clot formation
      and/or an increased risk of thrombosis. A need exists to identify more effective
      and safer methods to promote clotting in neonates. Objectives Procoagulant
      agents, such as prothrombin complex concentrates (PCCs) and recombinant activated
      factor VII (rFVIIa), are being used off-label to treat excessive bleeding in
      neonates after CPB. Because these agents stimulate endogenous fibrin formation,
      we hypothesize that their addition to post-CPB neonatal plasma will better
      recapitulate native clot properties than cryoprecipitate. Methods We analyze the
      structural, mechanical and degradation properties of fibrin matrices formed by
      neonatal plasma collected after CPB in the presence of an activated four-factor
      (F) PCC (FEIBA), rFVIIa, or cryoprecipitate using confocal microscopy, atomic
      force microscopy and a fluidics-based degradation assay. Results The ex vivo
      addition of FEIBA and rFVIIa to post-CPB neonatal plasma resulted in enhanced
      clot networks with differences in fibrin alignment, mechanics and degradation
      properties. Conclusions Our results suggest that these procoagulant agents could
      be used as an alternative to the transfusion of adult fibrinogen for the
      treatment of bleeding after CPB in neonates.

PMID- 30182423
TI  - Comparative Decellularization and Recellularization of Normal Versus
      Streptozotocin-Induced Diabetes Mellitus Rat Pancreas.
AB  - Decellularized (DC) organs/tissues offer a promising scaffold for regenerative
      bioengineering. However, it is not clear whether the diabetic mellitus (DM)
      pancreas can be used in decellularized and recellularized bioengineering. For
      assessment of these questions, murine pancreatic scaffolds of normal, type 1DM
      (T1DM) and type 2 DM (T2DM) pancreas were generated using a perfusion
      decellularization technique and assessed by histology, scanning electron
      microscopy, immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA).
      The capacity of DC pancreatic scaffolds to support attachment and proliferation
      of human umbilical vein endothelial cells (HUVECs) and MIN-6 beta cells was also
      assessed. Our results showed that DC pancreatic scaffolds were successfully
      produced from T1DM and T2DM pancreas and maintained their extracellular matrix
      (ECM) composition, 3D ultrastructure, and various cytokines. All of the
      pancreatic scaffolds were sufficiently cytocompatible and were able to support
      proliferation and adhesion of HUVECs and MIN-6 beta cells. The preliminary
      results support the biological utility of diabetes mellitus pancreatic scaffolds
      and pave the way for further investigations to assess the potential ability of
      using diabetes mellitus pancreas as scaffolds for recellularization and eventual
      medical applications.

PMID- 30182424
TI  - Identification of liver fibrosis using the hepatic vein waveform in patients with
      Fontan circulation.
AB  - AIM: Liver fibrosis caused by congestive hepatopathy has emerged as an important
      complication after Fontan procedure. We evaluated the utility of the hepatic vein
      (HV) waveform using Doppler ultrasound for identification of liver fibrosis in
      Fontan patients. METHODS: We investigated the HV waveforms in 41 Fontan patients
      and assessed correlations with clinical parameters, liver fibrosis markers, and
      hemodynamic data. RESULTS: Based on our preliminary analysis of 64 adult patients
      with chronic liver disease who underwent liver biopsy, we classified HV waveforms
      into five types with reference to the degree of flattening (from type 1, normal
      triphasic waveform; to type 5, a monophasic waveform indicating cirrhosis), and
      confirmed a significant correlation between waveform pattern and fibrosis stage.
      Notably, we detected HV waveforms in all of the Fontan patients and classified
      them into five types. The HV waveform pattern positively correlated with gamma
      glutamyl transferase and hyaluronic acid levels, and negatively correlated with
      albumin level and platelet count, but did not correlate with central venous
      pressure or brain natriuretic peptide level, suggesting that HV waveform could
      reflect pathophysiological changes in the liver without being affected by hepatic
      congestion. The highest area under the receiver operating characteristic curve of
      the HV waveform for detecting advanced liver fibrosis, as defined by ultrasonic
      findings and clinical features, was 0.829 (81.8% sensitivity, 73.3% specificity),
      which was higher than that of other non-invasive fibrosis markers. CONCLUSIONS:
      Hepatic vein waveforms change in accordance with liver fibrosis progression in
      Fontan patients, and can be a useful indicator of liver fibrosis after the Fontan
      procedure.

PMID- 30182425
TI  - Paclitaxel delivery system based on poly(lactide-co-glycolide) microparticles and
      chitosan thermo-sensitive gel for mammary adenocarcinoma treatment.
AB  - OBJECTIVES: To evaluate the combination of more than one release system in the
      same formulation as a useful strategy to achieve paclitaxel delivery in a more
      sustained and controlled manner. METHODS: The present study deals with the
      preparation of poly(lactide-co-glycolide) microparticles loaded with paclitaxel
      and included in a chitosan thermo-sensitive gelling solution. The microparticles
      were characterized by their size, shape and drug loading. The formulation was
      characterized by scanning electron microscopy, in vitro release experiments and
      was evaluated in mice bearing mammary adenocarcinoma. KEY FINDINGS: The formation
      of paclitaxel crystals in a pharmaceutical formulation reduces its efficacy. In
      this work, the use of microparticles avoided this phenomenon. Combining more than
      one delivery system allowed delivering paclitaxel in a more sustained and
      controlled manner leading to a long-term effect in the site of action. The
      formulation showed an inhibition in tumour volume of 63.0% in comparison with the
      control group. CONCLUSIONS: One intratumour injection of gelling solution
      containing the microparticles was at least as efficacious as four intraperitoneal
      injections of a commercial formulation. In addition, the delivery system was
      nontoxic, and the treated mice presented the highest percentage of tumour
      regression and median survival time.

PMID- 30182426
TI  - Plasma and synovial fluid concentrations and cartilage toxicity of bupivacaine
      following intra-articular administration of a liposomal formulation to horses.
AB  - BACKGROUND: The use of intra-articular (IA) local anaesthetics has proven to be
      an effective means to treat post-operative pain. The effects of local
      anaesthetics on equine chondrocytes are mixed with some studies reporting
      chondrodestruction and others no adverse effects. A liposomal formulation of
      bupivacaine is used in people and dogs by intra- and peri-articular
      administration to provide up to 72 h of analgesia. The potential uses, side
      effects including chondrotoxicity, and likelihood of abuse (long-term analgesic
      effects) has not been evaluated in horses. OBJECTIVES: Describe bupivacaine
      concentrations following IA administration and assess biomarkers as indicators of
      the effects of liposomal bupivacaine on chondrocytes in vivo. STUDY DESIGN:
      Parallel design. METHODS: Sixteen exercised horses received a single IA
      administration of 0.12 mg/kg liposomal bupivacaine or 0.9% saline. Blood and
      urine samples were collected for 96 h post-drug administration. Six horses
      treated with bupivacaine and those receiving saline, underwent daily
      arthrocentesis. Six additional bupivacaine treated horses underwent
      arthrocentesis at 96 h. Drug concentrations were measured using LC-MS/MS and
      pharmacokinetic analyses performed. Immunoassays were used to measure markers of
      collagen degradation (C2C, C12C) and cartilage matrix synthesis (CPII, CS846) in
      synovial fluid. RESULTS: The bupivacaine plasma elimination half-life was 17.8 +/
      5.42 and 11.9 +/- 5.17 h for horses from which synovial fluid was collected
      daily and at 96 h respectively. Bupivacaine concentrations in the joint were
      still detectable at 96 h. Significant increases in C12C and C2C were noted at 96
      h in horses undergoing arthrocentesis at 96 h only. CPII was increased at 48 h
      and CS846 at 24 and 48 h in horses sampled daily. MAIN LIMITATIONS: Limited
      number of animals and absence of liposome control group. CONCLUSIONS: Sustained
      concentrations of IA bupivacaine suggest viability of this medication as an intra
      articular analgesic. Effects on equine chondrocytes need further study.

PMID- 30182427
TI  - Mammalian meat allergy.
AB  - Mammalian meat allergy is an allergic reaction mediated by IgE antibodies
      directed against the mammalian oligosaccharide epitope galactose-alpha-1,3
      galactose. Clinically, it is characterized by a range of symptoms including
      urticaria, angioedema, gastroenteritis, and anaphylaxis hours following ingestion
      of red meat. It is an emergent allergy in tick endemic areas across the world. As
      a recently described disease with a cutaneous presentation, dermatologists should
      be familiar with this entity and recognize it as a differential diagnosis for
      urticarial and anaphylaxis reactions.

PMID- 30182428
TI  - Connectivity increases trophic subsidies in fragmented landscapes.
AB  - Landscape corridors mitigate the negative effects of habitat fragmentation by
      increasing dispersal. Corridors also increase biodiversity in connected habitat
      fragments, suggestive of metacommunity dynamics. What is unknown in this case is
      the mechanisms through which metacommunity dynamics act. Working in a large-scale
      fragmentation experiment, we tested the effect of corridors on the movement of
      prey species and subsequent effects on predator nutrition (which we call trophic
      subsidies). We enriched plants of central patches with 15 N, then measured
      delta15 N in green lynx spiders, the most abundant insect predator, in patches
      that were either connected to or isolated from the enriched patch. We found that
      corridors increased prey movement, as they increased spider delta15 N by 40% in
      connected patches. Corridors also improved spider body condition, increasing
      nitrogen relative to carbon. We suggest a novel mechanism, trophic subsidies,
      through which corridors may increase the stability or size of populations in
      connected landscapes.

PMID- 30182429
TI  - Heterogeneity of programmed death-ligand 1 expression in thymic epithelial
      tumours between initial specimen and synchronous or metachronous metastases or
      recurrences.

PMID- 30182430
TI  - Comparative pharmacokinetics of danofloxacin in healthy and Pasteurella multocida
      infected ducks.
AB  - Pasteurella multocida (P. multocida) infection causes substantial economic loss
      in the duck industry. Danofloxacin, a fluoroquinolone solely used in animals,
      shows good antibacterial activity against P. multocida. In this study, the in
      vitro pharmacodynamics of danofloxacin against P. multocida was studied. The
      serum and lung tissue pharmacokinetics of danofloxacin were studied in healthy
      and P. multocida infected ducks following oral administration of a single dose of
      5 mg/kg body weight (b.w.). The MIC, MBC and MPC of danofloxacin against P.
      multocida (C48-1 ) were 0.25, 1 and 3.2 MUg/ml, respectively. The Cmax was 0.34
      MUg/ml, attained at 2.03 hr in healthy ducks, and was 0.35 MUg/ml, attained at
      2.87 hr in diseased ducks. Compared to the serum pharmacokinetics of danofloxacin
      in healthy ducks, the absorption rate and extent were similar in healthy and
      diseased animals. In contrast, the elimination rate was slower, with an
      elimination half-life (T1/2beta ) of 13.17 and 16.18 hr for healthy and infected
      animals, respectively; the AUCs in the two groups were 5.70 and 7.68 MUg hr/ml,
      respectively, which means the total amount of drug in the circulation was
      increased in the infected ducks. The maximum concentration in lung tissues
      between healthy and infected animals was not significantly different (8.96 vs.
      8.93 MUg/g). However, the Tmax in healthy ducks was longer than that in infected
      ducks (4 hr vs. 1.75 hr), which means that the distribution rate of danofloxacin
      was slower in healthy ducks. The concentration of danofloxacin in lung tissues
      was approximately 24-fold higher than that in the serum. In the serum
      pharmacokinetic profiles, the fAUC0-24 hr /MIC was 18.19 in healthy ducks and was
      25.04 in P. multocida infected ducks at the clinical recommended dose, which is
      far from the PK/PD target (125 hr) of fluoroquinolones. Danofloxacin, at a dose
      of 5 mg/kg b.w., seems to be insufficient for ducks infected with P. multocida,
      with an MIC equal to 0.25 MUg/ml.

PMID- 30182431
TI  - Silver-Doped TiO2 -Coated Cotton Fabric as an Effective Photocatalytic System for
      Dye Decolorization in UV and Visible Light.
AB  - In this study, titanium tetra-isopropoxide was used as a precursor of TiO2 for in
      situ coating on cotton fabric by sol-gel method. Subsequently, silver nitrate was
      used as doping agent to prepare silver-doped TiO2 -coated cotton fabric during
      hydrothermal treatment. The treated samples were characterized through field
      emission scanning electron microscopy, energy-dispersive X-ray analysis,
      inductively coupled plasma-mass spectroscopy and UV-visible absorption
      spectroscopy to study morphology, composition of deposited elements and light
      absorption behavior of treated samples. X-ray photoelectron spectroscopy was
      carried out to analyze the electronic state of silver in TiO2 -coated fabric
      after hydrothermal treatment. Doping of silver on TiO2 -coated fabric and
      subsequent hydrothermal treatment was found to enhance dye decolorization rate of
      rhodamine B dye solution in both UV and visible light radiations with respect to
      undoped TiO2 . The study shows that an optimal level of silver-doped TiO2 -coated
      fabric can be used repeatedly for dye decolorization without significant loss in
      its photocatalytic activity. The self-cleaning properties of samples were also
      studied using methylene blue as a staining agent. It was observed that the
      presence of 1.8% silver on the weight of titanium in doped samples provides
      almost 82% of stain degradation.

PMID- 30182432
TI  - Effects of Medicare Medical Reviews on Ambiguous Short-Stay Hospital Admissions.
AB  - OBJECTIVE: To examine the effects of Medicare's Medical Review (MR) program on
      short-stay inpatient hospitalization. DATA SOURCES/STUDY SETTING: One Hundred
      percent of Medicare Part A and Part B claims and the Master Beneficiary Summary
      File (2007-2010). STUDY DESIGN: Retrospective observational study using a
      difference-in-differences approach. We examined six primary intake diagnoses, we
      believed likely to be targeted by MR. We stratified by hospital profit structure,
      bed size, system membership, and inpatient admission rate to test for
      differential effects. The comparison group was hospital visits occurring in those
      MACs that had yet to implement, as well as those that did not implement during
      the period of interest. DATA COLLECTION: None. PRINCIPAL FINDINGS: Medical Review
      significantly reduced the likelihood of inpatient admission for patients with an
      intake diagnosis of "Non-Specific Chest Pain" by 1.29 percentage points (p <
      .001). This effect was stronger in larger hospitals (-2.03, p < .001), nonsystem
      hospitals (-2.54, p < .001), and those with a lower inpatient rate (-1.86, p <
      .001). CONCLUSIONS: Short inpatient hospitalizations were emphasized by MR, and
      our results show that MR modestly reduced their prevalence among certain patients
      and certain hospitals. Future work should examine whether this resulted in
      adverse patient outcomes.

PMID- 30182433
TI  - Comprehensive analysis of differential circular RNA expression in a mouse model
      of colitis-induced colon carcinoma.
AB  - Circular RNAs (circRNAs) have received increasing attention for their involvement
      in the pathogenesis of cancer; however, the characterization and function of
      circRNAs in colitis-induced colon carcinoma remains largely unknown. A colitis
      induced colon carcinoma model was established in mice treated with azoxymethane
      dextran sodium sulfate (AOM-DSS), and the circRNA profile was screened by next
      generation sequencing. Bioinformatic tools, including Gene Ontology (GO)
      analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and
      network analysis were used to predict the functions of differentially expressed
      circRNAs and potentially coexpressed target genes. Among the detected candidate
      3069 circRNA genes, 126 circRNAs were upregulated, and 108 circRNAs were down
      regulated in colon tissues from AOM/DSS mice compared to those from control mice.
      A total of six of these candidate circRNAs were validated by RT-PCR. GO analysis
      revealed that numerous target genes including most microRNAs were involved in the
      Ras-Raf-MAPK pathway, actin cytoskeleton, focal adhesion, and additional
      biological processes. Our study revealed a comprehensive expression and
      functional profile for differentially expressed circRNAs in AOM/DSS induced colon
      carcinogenesis, indicating possible involvement of these dysregulated circRNAs in
      the development of colitis-induced colon carcinoma. The mmu-circ-001226/mmu-circ
      000287-miRNA-mRNA network may provide a potential mechanism for colitis
      associated colorectal cancer.

PMID- 30182434
TI  - Novel Extracorporeal Dialysis Circuit to Improve the Removal Efficiency of High
      and Middle Molecular Weight Toxins.
AB  - A new extracorporeal circuit for hemodialysis was designed with the goal of
      improving the middle and high molecular weight toxins removal. A recirculation
      pathway was added to the hemodialysis circuit and relevant pressure regulation
      was performed along the circuit in order to keep the ultrafiltration rate as
      zero. The influence of increasing the recirculation to dialysate flow rate ratio
      on the removal of urea, vitamin B12, and hemoglobin was investigated. This
      removal was also modeled by an analytical method and solved by MATLAB software. A
      significant increase in removal of vitamin B12 (34%) and especially hemoglobin
      (228%) was achieved using the recirculation flow in an adjusted hemodialysis
      circuit. The model showed an acceptable agreement with the experimental results
      which shows its applicability for prediction of different toxin removal in this
      circuit.

PMID- 30182435
TI  - Phenoloxidases are required for the pea aphid's defence against bacterial and
      fungal infection.
AB  - The pea aphid, Acyrthosiphon pisum, has an incomplete immune system compared to
      those of other insect species; some conserved components and pathways in other
      species are missing in its genome. As a core component of the insect immune
      system, prophenoloxidase (PPO) genes are retained in the pea aphid. Early studies
      have also shown the presence of phenoloxidase activity in specific tissues or
      cells in the pea aphid and suggested its involvement in response to immune
      challenges. In this study, we knocked down the expression of PPO genes in the pea
      aphid using double-stranded RNA-based interference, and quantitative PCR analysis
      and an enzyme activity assay confirmed our success in the PPO gene knockdown. In
      bacterial and fungal infection experiments, we observed that the knockdown of PPO
      resulted in more live bacterial cells and fungal spores in the body of the aphids
      and higher mortality of the aphids after infection. Our study provides evidence
      supporting a critical role of PPO in the defence of the pea aphid.

PMID- 30182436
TI  - Positive and negative social influences and crime acceleration during the
      transition from childhood to adolescence: The interplay of risk and protective
      factors.
AB  - BACKGROUND: Social influences are believed to play a vital role in delinquency
      development within the context of the child-to-adolescent transition. AIMS: It
      was hypothesised that (a) positive social influences would be at least as
      important as negative social influences in shaping later offending behaviour
      during the child-to-adolescent transition; (b) parental social influences would
      be more prominent during childhood, and sibling and peer social influences would
      be more prominent during adolescence; and (c) parents would have a more positive
      influence than siblings or peers. METHODS: Participants were 857 adult
      respondents (416 men, 441 women) from the 1942 and 1949 Racine birth cohorts.
      Most were White (87%), with 8% African Americans, and 5% Hispanics. Participants
      provided retrospective accounts of positive and negative social influences during
      childhood (ages 6-13) and offending both then and during adolescence (ages 14
      18). These retrospective accounts, which were organised into positive and
      negative influence scales by the original researchers, were then subjected to
      multiple regression analyses. RESULTS: A range of positive and negative social
      influences, not confined to parenting, were associated with adolescent offending,
      after allowing for the effects of sex, race, education, family structure, and
      parental and peer criminality. Change was a predominant theme in these data;
      whereas parental and sibling influences peaked during childhood and were
      overwhelmingly positive, peer influences peaked during adolescence and were less
      preponderantly positive. CONCLUSIONS AND IMPLICATIONS: These results support a
      risk model in which positive and negative social influences accumulate to
      determine a person's propensity for future offending. This propensity can be
      reduced by encouraging positive influences and discouraging negative ones during
      the child-to-adolescent transition.

PMID- 30182438
TI  - Spotlights on our sister journals: Angew. Chem. Int. Ed. 37/2018.

PMID- 30182437
TI  - Positive association between cholesterol in human seminal plasma and sperm
      counts: results from a cross-sectional cohort study and immunohistochemical
      investigations.
AB  - BACKGROUND: Cholesterol is essential for cell membrane stability, permeability,
      and fluidity. Cholesterol is present in seminal plasma, but whether a
      relationship between the level of cholesterol in seminal plasma and semen quality
      exists remains to be elucidated. OBJECTIVES: To explore the association between
      cholesterol levels in seminal plasma and serum cholesterols, semen quality, and
      serum reproductive hormones. Secondly, to explore whether the associations are
      biologically plausible. MATERIALS AND METHODS: An association study between
      cholesterol levels in seminal plasma and semen quality in 403 men, median age 19
      years, from the general population. Additionally, an immunohistochemical
      evaluation of proteins involved in cholesterol metabolism and transport in
      tissues from the male reproductive tract (testis, epididymis, prostate, and
      seminal vesicle). Tissue specimens were investigated by immunohistochemistry for
      markers of cholesterol metabolism and transport (ABCA1, ABCG1, CYP11A1, CYP51A1,
      HMGCR, LAL, LCAT, LDLR, and SOAT1). RESULTS: Trend analyses showed that total
      amount of total cholesterol in seminal plasma was positively associated with
      sperm concentration, total sperm count, sperm motility, and morphology (all p <
      0.008, adjusted). Cholesterol concentrations in seminal plasma were neither
      associated with serum cholesterol and lipid levels nor serum reproductive hormone
      (FSH, LH, testosterone, estradiol, sex-hormone-binding globulin, inhibin b)
      levels. All investigated markers of cholesterol metabolism and transport were
      expressed in the investigated tissue specimens to varying degrees. DISCUSSION:
      Seminal plasma level of cholesterol was positively associated with semen
      parameters. The presence of proteins and enzymes involved in cholesterol
      metabolism in Leydig cells, Sertoli cells, and maturing germ cells in the
      seminiferous tubules supports the view that cholesterol may be important for
      spermatogenesis. CONCLUSION: Cholesterol level in seminal plasma may be an
      indicator of semen quality. Investigations are needed to corroborate or refute
      our findings and to clarify the exact role of cholesterols for semen quality.

PMID- 30182439
TI  - Celecoxib alleviates AKT/c-Met-triggered rapid hepatocarcinogenesis by
      suppressing a novel COX-2/AKT/FASN cascade.
AB  - Previous studies have demonstrated that the selective cyclooxygenase-2 (COX-2)
      inhibitor celecoxib shows efficacy against multiple cancers, including
      hepatocellular carcinoma. However, whether celecoxib is effective in alleviating
      steatosis during hepatocarcinogenesis is unknown. In a rapid hepatocellular
      carcinoma (HCC) mouse model established via hydrodynamic transfection of
      activated forms of AKT and c-Met proto-oncogenes, we investigated the
      antisteatotic and anticarcinogenic efficacy of celecoxib in vivo. Multiple HCC
      cell lines were employed for in vitro evaluation. Additionally, immunoblotting,
      immunohistochemistry, hematoxylin and eosin staining and Oil Red O staining were
      applied for mechanistic investigation. The results revealed that if celecoxib was
      administered in the early stage of AKT/c-Met-induced HCC, it resulted in disease
      stabilization. Moreover, celecoxib could alleviate lipid accumulation in the HCC
      mice and in an oleic acid-induced in vitro hepatic steatosis model. Further
      evidence at the molecular level indicated that celecoxib down-regulated the
      expression of phospho-ERK (Thr202/Tyr204) and proliferating cell nuclear antigen
      (PCNA) in the HCC mice. In addition, celecoxib efficiently repressed the phosphor
      Akt (Thr308)/fatty acid synthase (FASN) axis both in vivo and in vitro.
      Altogether, this study suggests that celecoxib exerts its antilipogenic efficacy
      by targeting a COX-2/AKT/FASN cascade, which contributes to its ability to delay
      hepatocarcinogenesis.

PMID- 30182440
TI  - Neuropathology of holoprosencephaly.
AB  - Holoprosencephaly (HPE) is a primary disorder of neural induction and patterning
      of the rostral neural tube resulting in noncleavage of the forebrain with failure
      to form two separate distinct hemispheres. The spectrum of HPE is very broad and
      encompasses various neuropathological phenotypes of different severity. The
      recent literature has demonstrated that the phenotypic variability of HPE ranges
      from aprosencephaly-atelencephaly, at the most severe end, to milder forms such
      as the "middle interhemispheric variant" of HPE at the less severe end of the
      spectrum. Between them, different intermediate forms demonstrate a continuum in a
      wide phenotypic spectrum rather than well-defined categories. Although the term
      "HPE" suggests a disorder affecting only the prosencephalon, other brain
      structures are involved, underlining the complexity of the malformation. Because
      of close spatiotemporal interactions and common signaling pathways contributing
      to the development of both brain and face, concomitant facial and ocular
      anomalies are associated with brain malformation. In this review, the
      characteristic neuropathological features of the various forms of HPE are
      described as well as their associated brain, face, and ocular malformations, to
      delineate the different phenotypes.

PMID- 30182441
TI  - Challenging issues arising in counseling families experiencing holoprosencephaly.
AB  - The provision of information and support to families experiencing
      holoprosencephaly (HPE) in a loved one is unequivocally challenging, even for the
      most experienced clinicians. It deserves the balance of pertinent information
      coupled with medical guidance that forms the basis for shared decision-making;
      all of which is ideally contained within a supportive environment. It requires a
      willingness to carefully listen to the specific concerns of the parents and
      family allowing them to revisit challenging issues as much as needed to encourage
      existing road blocks to be resolved. It necessitates that professionals see each
      and every family as unique, without preconceived notions about what is or is not
      important and being prepared to accept thoughts and decisions that may not fit
      with the professional's own beliefs. To some, this may sound impractical,
      inefficient, or even impossible within the time constrained models of modern day
      clinical services. However, in practice, this patient-focused approach is
      arguably the most essential step in providing "personalized medicine" to the
      populations we encounter. This manuscript is intended to provide a brief review
      of relevant literature and case discussions to highlight issues for families
      learning of the diagnosis of HPE during a pregnancy, at birth, during childhood
      or more rarely, in adolescence.

PMID- 30182443
TI  - Introduction.

PMID- 30182444
TI  - Holoprosencephaly flashcards: An updated summary for the clinician.

PMID- 30182442
TI  - Cytogenetics and holoprosencephaly: A chromosomal microarray study of 222
      individuals with holoprosencephaly.
AB  - Holoprosencephaly (HPE), a common developmental forebrain malformation, is
      characterized by failure of the cerebrum to completely divide into left and right
      hemispheres. The etiology of HPE is heterogeneous and a number of environmental
      and genetic factors have been identified. Cytogenetically visible alterations
      occur in 25% to 45% of HPE patients and cytogenetic techniques have long been
      used to study copy number variants (CNVs) in this disorder. The karyotype
      approach initially demonstrated several recurrent chromosomal anomalies, which
      led to the identification of HPE-specific loci and, eventually, several major HPE
      genes. More recently, higher-resolution cytogenetic techniques such as
      subtelomeric multiplex ligation-dependent probe amplification and chromosomal
      microarray have been used to analyze chromosomal anomalies. By using chromosomal
      microarray, we sought to identify submicroscopic chromosomal deletions and
      duplications in patients with HPE. In an analysis of 222 individuals with HPE, a
      deletion or duplication was detected in 107 individuals. Of these 107
      individuals, 23 (21%) had variants that were classified as pathogenic or likely
      pathogenic by board-certified medical geneticists. We identified multiple
      patients with deletions in established HPE loci as well as three patients with
      deletions encompassed by 6q12-q14.3, a CNV previously reported by Bendavid et al.
      In addition, we identified a new locus, 16p13.2 that warrants further
      investigation for HPE association. Incidentally, we also found a case of Potocki
      Lupski syndrome, a case of Phelan-McDermid syndrome, and multiple cases of
      22q11.2 deletion syndrome within our cohort. These data confirm the genetically
      heterogeneous nature of HPE, and also demonstrate clinical utility of chromosomal
      microarray in diagnosing patients affected by HPE.

PMID- 30182445
TI  - Further evidence for complex inheritance of holoprosencephaly: Lessons learned
      from pre- and postnatal diagnostic testing in Germany.
AB  - Holoprosencephaly (HPE) has been defined as a distinct clinical entity with
      characteristic facial gestalt, which may-or may not-be associated with the true
      brain malformation observed postmortem in autopsy or in pre- or postnatal
      imaging. Affected families mainly show autosomal dominant inheritance with
      markedly reduced penetrance and extremely broad clinical variability even between
      mutation carriers within the same families. We here present advances in prenatal
      imaging over the last years, increasing the proportion of individuals with HPE
      identified prenatally including milder HPE forms and more frequently allowing to
      detect more severe forms already in early gestation. We report the results of
      diagnostic genetic testing of 344 unrelated patients for HPE at our lab in
      Germany since the year 2000, which currently with the application of next
      generation sequencing (NGS) panel sequencing identifies causal mutations for
      about 31% (12/38) of unrelated individuals with normal chromosomes when compared
      to about 15% (46/306) using conventional Sanger sequencing and Multiplex Ligation
      dependent Probe Amplification (MLPA). More comprehensive genetic testing by our
      in house NGS panel sequencing of 10 HPE associated genes (MiSeqTM and
      NextSeqTM500, Illumina, Inc., San Diego, CA) not only allowed to include genes
      with smaller contribution to the phenotype, but may also unravel additional low
      frequency or more common genetic variants potentially contributing to the
      observed large intrafamiliar variability and may ultimately guide our
      understanding of the individual clinical manifestation of this complex
      developmental disorder.

PMID- 30182446
TI  - Holoprosencephaly from conception to adulthood.
AB  - Holoprosencephaly (HPE) consists of a spectrum of malformations related to
      incomplete separation of the prosencephalon. There is a wide clinical variability
      depending on the HPE subtype seen on imaging. Early postnatal lethality is
      common, however a significant fraction of newborns diagnosed with HPE will
      survive into childhood and even adulthood. Here we will review the clinical
      management of HPE during different ages from the prenatal period to adulthood.

PMID- 30182447
TI  - The evolving role of zoological parks and aquariums in migratory bird
      conservation.
AB  - As threats to migratory birds in the Western Hemisphere, including North America,
      intensify and bird populations decline, there is a growing interest among zoo
      biologists in the conservation and management of these taxa. The purpose of this
      article is to explore the role that Association of Zoos and Aquariums (AZA)
      accredited zoos and aquariums either are playing or could play in the
      conservation and management of migratory birds. Topics explored include: (1)
      Public education and advocacy; (2) Captive breeding and reintroduction; (3) In
      situ conservation; (4) Tracking and monitoring; (5) Research/technology
      development; and (6) Sustainability/green practices; and (7) Partnerships. Zoos
      and aquariums could play an important role in increasing the public's access to
      understanding migratory birds and the threats they face, ultimately helping to
      protect these remarkable species.

PMID- 30182448
TI  - Targeting the overexpressed USP7 inhibits esophageal squamous cell carcinoma cell
      growth by inducing NOXA-mediated apoptosis.
AB  - Increasing evidence suggests that deubiquitinase USP7 participates in tumor
      progression by various mechanisms and serves as a potential therapeutic target.
      However, its expression and role in esophageal cancer remains elusive; the anti
      cancer effect by targeting USP7 still needs to be investigated. Here, we reported
      that USP7 was overexpressed in esophageal squamous cell carcinoma (ESCC) tissues
      compared with adjacent tissues, implying that USP7 was an attractive anticancer
      target of ESCC. Pharmaceutical or genetic inactivation of USP7 inhibited
      esophageal cancer cells growth in vitro and in vivo and induced apoptosis.
      Mechanistically, inhibition of USP7 accumulated poly-ubiquitinated proteins,
      activated endoplasmic reticulum stress, and increased expression of ATF4, which
      transcriptionally upregulated expression of NOXA and induced NOXA-mediated
      apoptosis. These results provide an evidence for clinical investigation of USP7
      inhibitors for the treatment of ESCC.

PMID- 30182449
TI  - Perception and knowledge of early pregnancy assessment units among perinatal
      practitioners in Europe.
AB  - OBJECTIVE: To investigate perceptions of early pregnancy assessment units (EPAUs)
      among perinatal practitioners working in Belgium, France, and Switzerland.
      METHODS: A prospective multinational survey was conducted between September 1,
      2015, and May 21, 2016. Obstetricians, gynecologists, medical doctors,
      radiologists, and midwives were recruited during meetings, via e-mail
      invitations, or through the websites of regional obstetrics and gynecology
      scientific societies. The survey comprised 17 questions that assessed the
      participants' knowledge, interest, and management of early pregnancy. RESULTS: Of
      the 871 individuals invited to participate in the survey, 306 (35.1%) responded.
      Most of the participants were gynecologists and/or obstetricians (225 [73.5%]). A
      total of 258 (84.3%) participants had no or limited knowledge about EPAUs.
      Furthermore, 211 (69.0%) participants reported incorrect management when they
      visualized a gestational sac without embryo and 265 (86.6%) misinterpreted
      changes in serum levels of chorionic gonadotropin during early pregnancy. In all,
      201 (65.7%) participants were interested in collaboration with an EPAU; however,
      only 125 (40.8%) had sufficient time and resources available to support a
      patient's psychological distress after early pregnancy loss or salpingectomy.
      CONCLUSION: Knowledge about early management of pregnancy was limited among the
      perinatal practitioners surveyed; however, the concept of EPAUs was welcomed by
      many.

PMID- 30182450
TI  - Dissecting the Mechanism of Oligomerization and Macrocyclization Reactions of
      NRPS-Independent Siderophore Synthetases.
AB  - Macrocyclic and linear hydroxamate siderophores produced by NRPS-independent
      siderophore (NIS; NRPS=nonribosomal peptide synthetase) synthetases are important
      in the bacterial competition for iron, as virulence factors, and as drugs for
      medical use in humans. Despite their importance, the mechanistic details of NIS
      synthetases have so far remained obscure. Using synthetic substrate analogues as
      tools allowed for an interrogation of the mechanism of the two closely related
      NIS synthetases AvbD and DesD. While AvbD produces macrocyclic homo- and
      heterodimers as native products, DesD is responsible for the synthesis of
      trimeric desferrioxamines. These enzymes comprise two adjacent binding sites with
      different substrate selectivities, which direct oligomerization and
      macrocyclization steps. Exploiting this difference, synthetic substrates were
      used to invert the native affinities for the sites resulting in switching from
      trimerization to dimerization reactions for DesD. Based on this work, a
      comprehensive model explaining the mechanistic details of the reactions and the
      differences between trimerizing and dimerizing enzymes was developed. Finally, a
      DesD mutant demonstrated the tuneability of the enzyme's substrate selectivity by
      only minor changes in the protein sequence. This finding confirms the affinity
      directed mechanism responsible for the iterativity of oligomerization and
      macrocyclization steps.

PMID- 30182451
TI  - Recent Advances of Optical Imaging in the Second Near-Infrared Window.
AB  - The near-infrared window between 1000 and 1700 nm, commonly termed the "second
      near-infrared (NIR-II) window," has quickly emerged as a highly attractive
      optical region for biological imaging. In contrast to conventional imaging in the
      visible region between 400 and 700 nm, as well as in the first NIR (NIR-I) window
      between 700 and 900 nm, NIR-II biological imaging offers numerous merits,
      including higher spatial resolution, deeper penetration depth, and lower optical
      absorption and scattering from biological substrates with minimal tissue
      autofluorescence. Noninvasive imaging techniques, specifically NIR-II
      fluorescence and photoacoustic (PA) imaging, have embodied the attractiveness of
      NIR-II optical imaging, with several NIR-II contrast agents demonstrating
      superior performance to the clinically approved NIR-I agents. Consequently, NIR
      II biological imaging has been increasingly explored due to its tremendous
      potential for preclinical studies and clinical utility. Herein, the progress of
      optical imaging in the NIR-II window is reported. Starting with highlighting the
      importance of biological imaging in the NIR-II spectral region, the emergence and
      latest development of various NIR-II fluorescence and PA imaging probes and their
      applications are then discussed. Perspectives on the promises and challenges
      facing this nascent yet exciting field are then given.

PMID- 30182452
TI  - LncRNA B4GALT1-AS1 recruits HuR to promote osteosarcoma cells stemness and
      migration via enhancing YAP transcriptional activity.
AB  - OBJECTIVES: This study aims to reveal the roles and related mechanisms of LncRNA
      B4GALT1-AS1 in osteosarcoma (OS) cells stemness and migration. MATERIALS AND
      METHODS: Real-time quantitative PCR (RT-qPCR) was used to detect the expression
      of several LncRNAs in OS tissues and normal adjacent tissues and in OS
      mammospheres and cells. Cell viability, transwell migration, tumour spheres
      formation and in vivo tumour formation assays were used to examine the effects of
      LncRNA B4GALT1-AS1 on OS progression. In addition, RNA immunoprecipitation (RIP)
      and Luciferase reporter assays were performed to determine the binding site of
      RNA-binding protein HuR on B4GALT1-AS1 and transcriptional factor YAP.
      Immunofluorescence analysis was used to examine YAP nuclear-cytoplasm
      translocation. RESULTS: LncRNA B4GALT1-AS1 expression was significantly increased
      in OS tissues and cells spheres. Knockdown of B4GALT1-AS1 inhibited OS cells
      proliferation, migration, stemness and chemotherapeutic sensitivity.
      Mechanistically, B4GALT1-AS1 recruited HuR to enhance YAP mRNA stability and thus
      its transcriptional activity. CONCLUSIONS: We indicate that lncRNA B4GALT1-AS1
      promotes OS cells stemness and migration via recruiting HuR to enhance YAP
      activity.

PMID- 30182453
TI  - Tracking Local Mechanical Impact in Heterogeneous Polymers with Direct Optical
      Imaging.
AB  - Structural heterogeneity defines the properties of many functional polymers and
      it is often crucial for their performance and ability to withstand mechanical
      impact. Such heterogeneity, however, poses a tremendous challenge for
      characterization of these materials and limits our ability to design them
      rationally. Herein we present a practical methodology capable of resolving the
      complex mechanical behavior and tracking mechanical impact in discrete phases of
      segmented polyurethane-a typical example of a structurally complex polymer. Using
      direct optical imaging of photoluminescence produced by a small-molecule
      organometallic mechano-responsive sensor we observe in real time how polymer
      phases dissipate energy, restructure, and breakdown upon mechanical impact. Owing
      to its simplicity and robustness, this method has potential in describing the
      evolution of complex soft-matter systems for which global characterization
      techniques fall short of providing molecular-level insight.

PMID- 30182454
TI  - UK Haemophilia Centre Doctors' Organisation guidance on the use of extended-half
      life coagulation factor concentrates in routine clinical practice: Report of a
      meeting on their adoption by Belgian haemophilia treaters.

PMID- 30182455
TI  - The effectiveness of a structured nursing intervention program on maternal stress
      and ability among mothers of premature infants in a neonatal intensive care unit.
AB  - AIMS AND OBJECTIVES: To investigate the effectiveness of a structured nursing
      intervention program on maternal stress and NICU-related maternal ability after
      the admission of premature infants to a neonatal intensive care unit (NICU).
      BACKGROUND: Mothers of premature infants may face stress having premature
      infants, and their infants may be admitted to the NICU for a few weeks or months.
      The mothers' experience of stress would be worse if they have low knowledge and
      poor NICU-related maternal ability. Mothers of infants admitted to the NICU
      require well-planned interventions to cope with psychological matters arising
      after an infant hospitalisation. DESIGN: Quasi-experimental design. METHODS: A
      total of 216 mothers were consecutively assigned to control and intervention
      groups. Each group consisted of 108 mothers. The mothers in both groups received
      questionnaire concerning maternal stress and NICU-related ability during their
      first visit to NICU (within 48 hr of admission). A structured nursing
      intervention was implemented for 10 days on mothers in the intervention group.
      The control group continued to receive existing practice nursing care. Mothers of
      both groups were again given the questionnaire on maternal stress and NICU
      related ability after 14 days of admission. RESULTS: In the intervention group,
      the difference between the mean total score of maternal stress and parental role
      and relationship subscale decreased significantly, compared to the control group
      (p = 0.04; p = 0.01) respectively. Maternal ability improved significantly in
      mothers in the intervention group 2 weeks postintervention, p < 0.001.
      CONCLUSION: A structured nursing intervention for mothers could significantly
      reduce maternal stress and promote maternal NICU-related abilities. RELEVANCE TO
      CLINICAL PRACTICE: The results of the study could help neonatal nurses to develop
      an appropriate nursing intervention for parents with premature infants in the
      NICU.

PMID- 30182456
TI  - Synthesis of Trifluoromethyl-alpha,beta-unsaturated Lactones and Pyrazolinones
      and Discovery of Influenza Virus Polymerase Inhibitors.
AB  - To explore the potential biological activities of trifluoromethyl heterocycles,
      we recently developed a synthetic approach to access a series of alpha
      trifluoromethyl-alpha,beta-unsaturated lactones and trifluoromethyl
      pyrazolinones. The compounds were tested for their antimicrobial activity, and we
      found that some compounds had anti-influenza viral activity. The beta-aryl-alpha
      trifluoromethyl alpha,beta-unsaturated lactone derivatives 5 g (5-(4
      chlorophenyl)-5-methyl-4-phenyl-3-(trifluoromethyl)furan-2-one), 7 b (4-(4
      methoxyphenyl)-3-(trifluoromethyl)spiro[furan-5,1'-indane]-2-one), and the
      trifluoromethyl pyrazolinone 12 c (1-(6-methoxy-2-naphthyl)-2-(trifluoromethyl)
      5,6,7,8-tetrahydropyrazolo[1,2-a]pyridazin-3-one) were found to possess promising
      inhibitory activity against influenza virus type A, strain A/WSN/33 (H1N1). These
      three hit compounds were successfully optimized, and we identified that the most
      potent compound 5 h (5-(4-chlorophenyl)-4-(6-methoxy-2-naphthyl)-5-methyl-3
      (trifluoromethyl)furan-2-one) showed inhibitory activity against various types of
      influenza A and B viruses in the low-micromolar range without showing
      cytotoxicity. Moreover, 5 h was more effective against the clinical isolate
      A/California/7/2009 (H1N1pdm) strain than the influenza viral polymerase
      inhibitor, favipiravir (T-705). We also delineated the structure-activity
      relationship and obtained mechanistic insight into inhibition of the viral
      polymerase.

PMID- 30182457
TI  - Breastfeeding, schooling, and income: Insights from the Indonesian Family Life
      Survey.
AB  - Recent research has highlighted associations of breastfeeding with IQ, schooling,
      and income, but uncertainty about such links remains. The Indonesian Family Life
      Survey, representative of 83% of the Indonesian population, provides data on
      breastfeeding, parents' years of schooling, wealth, and other family
      characteristics in 1993-1994, as well as schooling and income in 2014-2015 for
      5,421 children of those families. Using linear regressions and controlling for
      village or neighbourhood, as well as propensity score matching, we analysed
      breastfeeding associations for boys and girls separately, when regularly fed
      foods/beverages other than breast milk is significantly associated with years of
      schooling in 2014-2015 for girls, but not for boys, after controlling for the
      village or neighbourhood of residence in 1993-1994. For girls, ages 1 to 1.9, 2
      to 2.9, 3 to 3.9, and >4 months, relative to ages <1 month, are associated with
      an additional 0.41 to 0.46 years of schooling, with p values of 0.086, 0.071,
      0.043, and 0.026, respectively. No comparable estimate for boys attains
      statistical significance. Using propensity score matching yields similar results.
      Associations with annual income in 2014-2015 are not statistically significant,
      either for all children, or for either sex. Our finding suggests that delaying
      regular feeding of foods/beverages other than breast milk beyond 1 month may help
      girls' schooling but has no observable association with annual income, perhaps
      because of lower labour force participation by women. Also, the inclusion of
      controls for village or neighbourhood of residence reduces confounding.

PMID- 30182458
TI  - Antivirals With Corticosteroids for the Treatment of Acute Bell's Palsy.

PMID- 30182459
TI  - Skin fiducial markers enable accurate computerized navigation resection of
      simulated soft tissue tumors: A static cadaveric model pilot study.
AB  - BACKGROUND: This static cadaveric model pilot study evaluated the agreement
      between planned and resected margins of simulated soft tissue tumors (SSTT) using
      skin fiducial markers for computerized navigation registration. METHODS: Markers
      were applied before magnetic resonance imaging scans of lower extremities
      implanted with SSTT. A navigation pointer was used for registration and to guide
      SSTT resection with approximately 10 mm planned margins. Digital calipers were
      used to measure resection margins. Kolmogorov-Smirnov tests were used to confirm
      measurement normality. A one-sample t test was used to determine measurement
      group differences (P <= 0.05). Bland-Altman analysis and histogram plots compared
      planned and resected margins. RESULTS: Ninety-eight resection margins were
      measured. The planned margin mean was 10.0 mm (95% confidence interval [CI] = 9.8
      10.2 mm) and the resected margin mean was 11.5 mm (95% CI = 11.0-12.1 mm). One
      sample t test results identified a 0.75 mm, 95% CI = 0.5-0.99 mm difference (P <
      0.001). Good measurement agreement was observed with 94.9% (93/98) of resections
      occurring within two standard deviations of the mean measurement difference.
      CONCLUSIONS: Skin fiducial marker use for computerized navigation system
      registration displayed promising results. With further research, these markers
      may become an effective, noninvasive method for aiding in soft tissue tumor
      resection.

PMID- 30182460
TI  - Impact of subsidized fortified wheat on anaemia in pregnant Indian women.
AB  - The World Health Assembly called for a 50% global anaemia reduction in women of
      reproductive age (15-49 years of age) from 2012 to 2025. India accounts for the
      most cases of anaemia in the world, and half of all pregnant Indian women are
      anaemic. In India, the government implemented a 4-year food-based safety net
      programme from 2008 to 2012 involving the provision of fortified wheat flour
      through its public distribution system. We assessed programme impact on anaemia
      among pregnant women (n = 10,186) using data from the 2002-2004 and 2012-2013
      Indian District Level Health Surveys. The difference-in-differences method was
      used to estimate the impact on haemoglobin (Hb) and anaemia in pregnant women
      living in northern India (Punjab) and southern India (Tamil Nadu), with pregnant
      women in neighbouring states without wheat fortification programmes serving as
      controls. In northern India, we found no impact on Hb (beta = -0.184, P = 0.793)
      or anaemia reduction (beta = -0.01, P = 0.859), as expected, given that the
      intervention targeted only nonpoor households and demand for fortified wheat was
      low. In southern India, where intervention coverage was high, we found no impact
      on Hb (beta = -0.001, P = 0.998) but did see an impact on anaemia reduction (beta
      = -0.08, P = 0.042), which was unexpected given low consumption of wheat in this
      predominantly rice-eating region. India's wheat fortification programmes were
      largely ineffective in terms of reducing anaemia among pregnant women. As
      policymakers expand fortification programs, it is critical to ensure that the
      fortified food is universally available and distributed widely through well
      functioning and popular outlets.

PMID- 30182461
TI  - Cone beam CT for QA of synthetic CT in MRI only for prostate patients.
AB  - PURPOSE: Magnetic resonance imaging (MRI)-only radiotherapy is performed without
      computed tomography (CT). A synthetic CT (sCT) is used for treatment planning.
      The aim of this study was to develop a clinically feasible quality assurance (QA)
      procedure for sCT using the kV-cone beam CT (CBCT), in an MRI-only workflow for
      prostate cancer patients. MATERIAL AND METHOD: Three criteria were addressed;
      stability in Hounsfield Units (HUs), deviations in HUs between the CT and CBCT,
      and validation of the QA procedure. For the two first criteria, weekly phantom
      measurements were performed. For the third criteria, sCT, CT, and CBCT for ten
      patients were used. Treatment plans were created based on the sCT (MriPlannerTM
      ). CT and CBCT images were registered to the sCT. The treatment plan was copied
      to the CT and CBCT and recalculated. Dose-volume histogram (DVH) metrics were
      used to evaluate dosimetric differences between the sCT plan and the recalculated
      CT and CBCT plans. HU distributions in sCT, CT, and CBCT were compared. Well
      defined errors were introduced in the sCT for one patient to evaluate efficacy of
      the QA procedure. RESULTS: The kV-CBCT system was stable in HU over time
      (standard deviation <40 HU). Variation in HUs between CT and CBCT was <60 HU. The
      differences between sCT-CT and sCT-CBCT dose distributions were below or equal to
      1.0%. The highest mean dose difference for the CT and CBCT dose distribution was
      0.6%. No statistically significant difference was found between total mean dose
      deviations from recalculated CT and CBCT plans, except for femoral head.
      Comparing HU distributions, the CBCT appeared to be similar to the CT. All
      introduced errors were identified by the proposed QA procedure, except all tissue
      compartments assigned as water. CONCLUSION: The results in this study shows that
      CBCT can be used as a clinically feasible QA procedure for MRI-only radiotherapy
      of prostate cancer patients.

PMID- 30182462
TI  - Nonpharmacological treatment for individuals with intellectual disability and
      "personality disorder".
AB  - BACKGROUND: Research exploring nonpharmacological interventions for individuals
      with intellectual disability and personality disorder was reviewed. This should
      prove valuable to services and professionals contemplating how to offer
      interventions for these individuals. METHOD: A systematic search of electronic
      databases was conducted. Articles were considered for inclusion according to
      criteria based on the PICOS model. The quality of the research was assessed
      utilizing the evaluative method for determining evidence-based practice. RESULTS:
      Eleven studies were reviewed with quality assessment indicating that all provided
      weak research evidence. Consistent flaws included insufficient description of
      participants and lack of control groups. CONCLUSIONS: The research base exploring
      nonpharmacological interventions for individuals with intellectual disabilities
      and personality disorder includes many methodological flaws but reveals some
      useful information regarding the characteristics of these individuals and
      components of interventions to support them. Further research is needed to
      identify the differential effectiveness of interventions over and above other
      confounding factors.

PMID- 30182463
TI  - A dual-tuned 13 C/1 H head coil for PET/MR hybrid neuroimaging: Development,
      attenuation correction, and first evaluation.
AB  - PURPOSE: This study aims to develop, implement, and evaluate a dual-tuned 13 C/1
      H head coil for integrated positron emission tomography/magnetic resonance
      (PET/MR) neuroimaging. The radiofrequency (RF) head coil is designed for
      optimized MR imaging performance and PET transparency and attenuation correction
      (AC) is applied for accurate PET quantification. MATERIAL AND METHODS: A dual
      tuned 13 C/1 H RF head coil featuring a 16-rung birdcage was designed to be used
      for integrated PET/MR hybrid imaging. While the open birdcage design can be
      considered inherently PET transparent, all further electronic RF components were
      placed as far as possible outside of the field-of-view (FOV) of the PET
      detectors. The RF coil features a rigid geometry and thin-walled casing.
      Attenuation correction of the RF head coil is performed by generating and
      applying a dedicated 3D CT-based template attenuation map (MUmap). Attenuation
      correction was systematically evaluated in phantom experiments using a large
      volume cylindrical emission phantom filled with 18-F-Fluordesoxyglucose (FDG)
      radiotracer. The PET/MR imaging performance and PET attenuation correction were
      then evaluated in a patient study including six patients. RESULTS: The dual-tuned
      RF head coil causes a mean relative attenuation difference of 8.8% across the
      volume of the cylindrical phantom, while the local relative differences range
      between 1% and 25%. Applying attenuation correction, the relative difference
      between the two measurements with and without RF coil is reduced to mean value of
      0.5%, with local differences of +/-3.6%. The quantitative results of the phantom
      measurements were corroborated by patient PET/MR measurements. Patient scans
      using the RF head coil show a decrease of PET signal of 5.17% +/- 0.81% when
      compared to the setup without RF head coil in place, which served as a reference
      scan. When applying attenuation correction of the RF coil in the patient
      measurements, the mean difference to a measurement without RF coil was reduced to
      -0.87% +/- 0.65%. CONCLUSION: A dual-tuned 13 C/1 H RF head coil was designed and
      evaluated regarding its potential use in integrated PET/MR hybrid imaging.
      Attenuation correction was successfully applied. In conclusion, the RF head coil
      was successfully integrated into PET/MR hybrid imaging and can now be used for 13
      C/1 H multinuclear hybrid neuroimaging in future studies.

PMID- 30182464
TI  - Perforating vessel as an alternative option of a recipient selection for
      posterior trunk-free flap reconstruction.
AB  - BACKGROUND: The reconstruction of complex defects in the posterior trunk is a
      challenging problem. Various surgical methods using local flap, propeller flap,
      and muscle flap have been reported. However, in case where a free flap is
      inevitable, due to the absence of usable recipient vessels, eventually it may
      fail to perform or the use of long vessel graft is mandatory. To overcome this
      problem, we investigated use of perforator as recipient vessel in posterior trunk
      region and here we report satisfactory outcomes of the cases. PATIENTS AND
      METHODS: Eighteen cases with posterior trunk defects underwent reconstruction
      surgeries using various free flaps. Perforating vessels, from either the base or
      margin of the defect, were evaluated by preoperative computed tomography and hand
      held Doppler. During the dissection, preoperatively marked perforators, with
      visual healthy pulsation and appropriate diameter for anastomosis, were selected
      and used for a recipient vessel for free flap. RESULTS: Perforating vessels from
      the posterior trunk (0.8-1.3 mm in diameter) were used as recipient vessels and
      the average size of the defect was 85.2 cm2 . In all cases, one artery and vein
      was used for anastomosis. No flap necrosis occurred. Hematoma developed in one
      case and partial wound disruption developed in 2 cases. CONCLUSION: Surgical
      method using perforators as recipients for free flap reconstruction can be one of
      a good treatment option for posterior trunk reconstruction. We think that
      microsurgeons need not to hesitate when they use perforating vessel as a
      recipient vessel.

PMID- 30182465
TI  - Treatment of penile actinomycosis.

PMID- 30182466
TI  - Microbial keratitis associated with long-term orthokeratology.

PMID- 30182467
TI  - Developing Graphene-based Nanohybrids for Electrochemical Sensing.
AB  - Graphene-based nanohybrid is considered to be the most promising nanomaterial for
      electrochemical sensing applications due to the defects created on the graphene
      oxide layers. These defects provide graphene oxide unique properties, such as
      excellent conductivity, large specific surface area, and electrocatalytic
      activity. These unique properties encourage scientists to develop novel graphene
      based nanohybrids and improve the sensing efficiency. This review, therefore,
      addresses this topic by comprehensively discussing the strategies to fabricate
      novel graphene based nanohybrids with high sensitivity. The combinations of
      graphene with various nanomaterials, such as metal nanoclusters, metal compound
      nanoparticles, carbon materials, polymers and peptides, in the direction of
      electrochemical sensing, were systematically analyzed. Meanwhile, the challenges
      in the functional design and application of graphene-based nanohybrids were
      described and the reasonable solutions were proposed.

PMID- 30182468
TI  - The predictive value of factor VIII/factor IX levels to define the severity of
      hemophilia: communication from the SSC of ISTH.

PMID- 30182470
TI  - Trials Abstracts.

PMID- 30182469
TI  - Abstracts of the 13th Scientific and Annual Meeting of the European Society of
      Coloproctology, Nice Acropolis Palais des Congres, 26-28 September 2018.

PMID- 30182471
TI  - Quantitative analysis of finasteride tablets dissolution content with non
      isotopically labeled internal standard by paper spray ionization mass
      spectrometry.
AB  - Paper spray ionization, one of the ambient mass spectrometry technologies, has
      been developed to characterize the content of drugs in various complex matrixes
      including urine, whole blood, dissolution solutions, and so on. An isotopically
      labeled compound as internal standard is often used in quantitative paper spray
      ionization experiments. But high cost and difficult to access impede the
      application of this type of internal standards. Application of non-isotopically
      labeled compounds as internal standards will make this technology more prevalent.
      In this paper, we explored the application of finasteride impurity as the
      internal standard in paper spray ionization-mass spectrometry to measure the
      dissolution content of finasteride tablets. The new method was optimized and the
      results were compared to those from high-performance liquid chromatography. The
      whole analysis time was several minutes and limit of detection for finasteride
      was around 4.8 ng/mL. The results from paper spray ionization-mass spectrometry
      were similar to those from high-performance liquid chromatography. Combination of
      paper spray ionization-mass spectrometry and non-isotopically labeled internal
      standard renders a new method to analyze drug dissolution content with high
      specificity, low limit of detection, and simple sample preparation within short
      time period.

PMID- 30182472
TI  - Identification and characterization of dendritic cell subtypes in preserved and
      cultured cadaveric human corneolimbal tissue on amniotic membrane.
AB  - PURPOSE: Rejection is the leading cause of failure of limbal allogafts. Resident
      dendritic cell (DC) maturation plays a critical role in host allosensitization.
      There are two lineages: myeloid (mDC) and lymphoid (pDC), with different
      biological properties. The aim was to analyse the distribution of DC subtypes in
      limbal explant cultures on amniotic membrane (AM), cultivated on either the
      epithelial or stromal side and to compare the results with directly isolated
      cells from cadaveric whole corneoscleral tissue divided into specific areas.
      METHODS: The expression of CD11c (mDC), CD303/CD123 (pDC) and costimulatory
      molecules CD80, CD86 and activation markers HLA-DR, CD83 was investigated by flow
      cytometry. Additionally, the corneal epithelium marker CK12 and ABCB5, a new
      epithelial stem cell marker, were investigated. RESULTS: Cells positive for pDC
      and mDC markers were found in all examined areas, with a nonsignificant
      prevalence of pDC. In limbal explant cultures on AM, the percentage of pDC and
      mDC was similar, with no statistically significant difference between cultures on
      epithelial or stromal sides of AM. However, with ex vivo limbal explant
      cultivation on AM, the pDC content declined significantly (p < 0.05) and the
      ABCB5 marker was likewise statistically significantly reduced. CONCLUSION: This
      is the first study to characterize the distribution of pDC and mDC subsets in
      cultured and noncultured human corneolimbal tissue. Additionally, ABCB5 positive
      cells were identified. These findings might be important for future strategies,
      allowing preparation of corneolimbal allografts with optimal stem cell content
      for a longer lasting therapeutic effect.

PMID- 30182473
TI  - Sustained vasomotor control of skin microcirculation in Sherpas versus altitude
      naive lowlanders: Experimental evidence from Xtreme Everest 2.
AB  - NEW FINDINGS: What is the central question of this study? Do Sherpa highlanders,
      when exposed to graded hypobaric hypoxia, exhibit enhanced vasomotor and
      neurovascular control to maintain microcirculatory flux, and thus tissue
      oxygenation, when compared with altitude-naive lowlanders? What is the main
      finding and its importance? Sherpas, when exposed to hypobaric hypoxia at high
      altitude, demonstrated superior preservation of their peripheral microcirculatory
      perfusion, a greater oxygen unloading rate and sustained microvascular reactivity
      with enhanced vasomotion, when compared with altitude-naive lowlanders. These
      differences have not been reported previously and may improve our understanding
      of the multifactorial responses to sustained environmental hypoxia. ABSTRACT:
      Enhanced oxygen delivery, consequent to an increased microvascular perfusion, has
      been postulated to play a key role in the physiological adaptation of Tibetan
      highlanders to the hypobaric hypoxia encountered at high altitude. We tested the
      hypothesis that Sherpas, when exposed to graded hypobaric hypoxia, demonstrate
      enhanced vasomotor and neurovascular control to maintain microcirculatory flux,
      and thus tissue oxygenation, when compared with altitude-naive lowlanders. Eighty
      three lowlanders [39 men and 44 women, 38.8 (13.1) years old; mean (SD)] and 61
      Sherpas [28 men and 33 women, 27.9 (6.9) years old] were studied on ascent to
      Everest Base Camp over 11 days. Skin blood flux and tissue oxygen saturation were
      measured simultaneously using combined laser Doppler fluximetry and white light
      spectroscopy at baseline, 3500 and 5300 m. In both cohorts, ascent resulted in a
      decline in the sympathetically mediated microvascular constrictor response (P <
      0.001), which was more marked in lowlanders than in Sherpas (P < 0.001). The
      microvascular dilator response evaluated by postocclusive reactive hyperaemia was
      significantly greater in Sherpas than in lowlanders at all sites (P < 0.002).
      Spectral analysis of the blood flux signals revealed enhanced myogenic
      (vasomotion) activity in Sherpas, which was unaffected by ascent to 5300 m.
      Although skin tissue oxygenation was lower in Sherpas than in lowlanders, the
      oxygen unloading rate was faster, and deoxyhaemoglobin levels higher, at all
      altitudes. Together, these data suggest that Sherpas, when exposed to hypobaric
      hypoxia, demonstrated superior preservation of peripheral microcirculatory
      perfusion compared with altitude-naive lowlanders. The physiological differences
      in local microvasculature vasomotor and neurovascular control may play a key role
      in Sherpa adaptation to high-altitude hypobaric hypoxia by sustaining local
      perfusion and tissue oxygenation.

PMID- 30182474
TI  - The effect of maternity practices on exclusive breastfeeding rates in U.S.
      hospitals.
AB  - The Baby-friendly Hospital Initiative (BFHI) includes a set of 10 evidenced-based
      maternity practices that when used together have been shown to improve
      breastfeeding outcomes. In 2007, the Centers for Disease Control and Prevention
      launched the Maternity Practices in Infant Nutrition and Care (mPINC) survey to
      assess and monitor these and other evidenced-based maternity practices. The
      purpose of this study was to explore individual maternity practices measured in
      the 2013 mPINC survey, along with hospital demographic information, and their
      relationships with exclusive breastfeeding (EBF) rates, using a sample of United
      States (U.S.) hospitals. We obtained mPINC survey data from 69 BFHI hospitals and
      654 non-BFHI hospitals in the U.S., and EBF rates from The Joint Commission, a
      leading hospital accreditation agency. On the basis of linear regression
      analysis, we found that most maternity practices studied were significantly
      associated with EBF rates (max adjusted R2  = 14.9%). We found a parsimonious
      model with an adjusted R2 of 47.3%. This study supports the need for a systematic
      approach in providing breastfeeding support as no one maternity care practice was
      able to explain the variability in EBF rates as well as a collection of maternity
      care practices.

PMID- 30182475
TI  - Analysis of differentially expressed genes and the promoters in bovine
      endometrium throughout estrus cycle and early pregnancy.
AB  - Endometrial gene expression is primarily regulated by the ovarian steroids and
      pregnancy recognition factors. This study was aimed to characterize differential
      expression genes (DEGs) in bovine endometrium together with the analysis of their
      promoter region. Bovine uteri at follicular stage (FS), luteal stage (LS), and
      implantation stage (IS) at Day 18 of pregnancy were collected. Total RNA
      extracted and prepared cDNA were then subjected to high-throughput sequencing.
      For promoter analysis, 1 kb upstream promoter region of each DEG was analyzed.
      The numbers of highly expressed DEGs were 496 and 597 at FS and LS, respectively.
      When compared the gene expression of IS with LS, 383 and 346 DEGs showed higher
      and lower expression at IS, respectively. It was also observed that 20-30
      transcription factors (TFs) were included in each DEGs. In addition, promoter
      analyses estimated 150-160 TFs for each stage. DLX4 and interferon regulatory
      factor 4 (IRF4) at FS, and IRF5, IRF9, STAT1, and STAT2 at IS were in common to
      DEGs and estimated TFs, respectively. This study highlighted potential molecular
      mechanisms controlling endometrial function during estrus cycle and IS, which
      will further guide to better understand the endometrial functions in future
      studies.

PMID- 30182476
TI  - Sensitization to, and allergic contact dermatitis caused by, colophonium in north
      eastern Italy in 1996 to 2016 with a focus on occupational exposures.
AB  - BACKGROUND: Colophonium is a natural substance derived from Pineaceae trees. It
      is used in a wide range of consumer and occupational products because of its
      tackiness, and is a known sensitizer. OBJECTIVES: To analyse the temporal trend
      of contact allergy to colophonium in north-eastern Italy, and to evaluate the
      associations with occupations in our geographical area. METHODOLOGY: From 1996 to
      2016, 27 381 patients with suspected allergic contact dermatitis were patch
      tested in north-eastern Italy. Individual characteristics were documented by use
      of a standardized questionnaire in 6 departments of dermatology or occupational
      medicine. RESULTS: The overall prevalence of colophonium sensitization was 1.67%;
      the prevalence was significantly higher in women (1.75%) than in men (1.49%). No
      significant differences among departments were observed. We found significant
      associations between colophonium sensitization and being a student (odds ratio
      [OR] 4.64; 95% confidence interval [CI]: 1.04-20.6), being a farmer or fishermen
      (OR 3.63; 95%CI: 1.21-10.84), being a housekeeper (OR 2.02; 95%CI: 1.08-3.77),
      and being retired (OR 2.06; 95%CI: 1.08-3.92). CONCLUSION: Our study showed that
      contact allergy to colophonium is still relevant in north-eastern Italy. The
      frequency of sensitization has dropped significantly over a period of 10 years,
      but students and farmers/fishermen still have sensitization prevalences above
      3.5%. Our results are in line with European data.

PMID- 30182477
TI  - Views of key stakeholders on the causes of patient falls and prevention
      interventions: A qualitative study using the international classification of
      functioning, disability and health.
AB  - AIMS AND OBJECTIVES: To examine the views and suggestions of healthcare
      professionals, patients and family members on the causes of inpatient falls and
      fall-prevention practices. BACKGROUND: Patient falls are one of the most
      prevalent medical errors in the hospitals. In order to prevent patient falls, it
      is necessary to identify and classify the situations causing falls in detail and
      preventive interventions for these situations need to be developed. DESIGN: The
      study was designed using a descriptive qualitative research method. METHOD: The
      semi-structured interviews were conducted with four physicians, four charge
      nurses, 12 nurses, four support staff members, eight patients and eight family
      members of patients in the palliative, internal disease, surgery and orthopaedic
      clinics in a training and research hospital between March 2017-May 2017. Thematic
      analysis method was used to analyse data. The defined themes were classified
      based on the International Classification of Functioning, Disability and Health
      Core Set for Falls in Acute Rehabilitation Settings. RESULTS: In this research,
      71 themes related to situations causing falls and 30 themes related to prevention
      interventions were determined. Defined themes were linked with 44 categories
      under five International Classification of Functioning, Disability and Health
      domains and organised accordingly. Among the categories included in the
      International Classification of Functioning, Disability and Health Core Set for
      Falls in Acute Rehabilitation Settings, 65% were verified, while 22 new
      categories that were not included in the original core set were defined.
      CONCLUSION: In accordance with this result, evaluating the opinions of all
      stakeholders on the research and development of fall-prevention programmes will
      increase the effectiveness of fall prevention in hospitals. The ICF model can be
      used to classify the causes of falls and fall-prevention interventions to create
      a common language about this topic. RELEVANCE TO CLINICAL PRACTICE: To prevent
      falls, more detailed and useful information can be obtained by key stakeholders
      (all healthcare professionals, patient and patient family). ICF Core Set For
      Falls can be used to systematically classify causes of falls and fall-prevention
      interventions.

PMID- 30182478
TI  - Coronary artery calcium and intima-media thickness are associated with level of
      cytomegalovirus immunoglobulin G in HIV-infected patients.
AB  - Coinfection with cytomegalovirus (CMV) may be involved in cardiovascular disease
      in HIV-infected patients. We found that higher level of CMV immunoglobulin G
      (IgG) was independently associated with an increased risk of coronary artery
      calcium and higher intima-media thickness in HIV-infected patients but not in
      healthy controls after adjustment for other cardiovascular risk factors and
      levels of herpes viridae IgG.

PMID- 30182479
TI  - Molecular Conformation-Dependent Mechanoluminescence: Same Mechanical Stimulus
      but Different Emissive Color over Time.
AB  - A phenothiazine derivative of FCO-CzS with changeable mechanoluminescence is
      reported, which, upon continuous mechanical stimulus, shows mechanoluminescent
      emission from blue to white and yellow. Careful analysis of the experimental
      results, coupled with the well-understood photoluminescence theory, show that the
      molecular conformation transition of the phenothiazine group from quasi-axial to
      quasi-equatorial is responsible for this dynamic mechanoluminescence effect.

PMID- 30182480
TI  - Rapid aggregative and reproductive responses of weevils to masting of North
      American oaks counteract predator satiation.
AB  - The predator satiation hypothesis posits that masting helps plants escape seed
      predation through starvation of predators in lean years, followed by satiation of
      predators in mast years. Importantly, successful satiation requires sufficiently
      delayed bottom-up effects of seed availability on seed consumers. However, some
      seed consumers may be capable of quick aggregative and reproductive responses to
      masting, which may jeopardize positive density dependence of seed survival. We
      used a 17-yr data set on seed production and insect (Curculio weevils)
      infestation of three North American oaks species (northern red Quercus rubra,
      white Q. alba, and chestnut oak Q. montana) to test predictions of the predation
      satiation hypothesis. Furthermore, we tested for the unlagged numerical response
      of Curculio to acorn production. We found that masting results in a bottom-up
      effect on the insect population; both through increased reproductive output and
      aggregation at seed-rich trees. Consequently, mast seeding in two out of three
      studied oaks (white and chestnut oak) did not help to escape insect seed
      predation, whereas, in the red oak, the escape depended on the synchronization of
      mast crops within the population. Bottom-up effects of masting on seed consumer
      populations are assumed to be delayed, and therefore to have negligible effects
      on seed survival in mast years. Our research suggests that insect populations may
      be able to mount rapid reproductive and aggregative responses when seed
      availability increases, possibly hindering satiation effects of masting. Many
      insect species are able to quickly benefit from pulsed resources, making
      mechanisms described here potentially relevant in many other systems.

PMID- 30182481
TI  - Elective repeat cesarean delivery in women eligible for trial of labor in Brazil.
AB  - OBJECTIVE: To assess the hospital, maternal, and obstetric characteristics
      associated with elective repeat cesarean delivery (ERCD) among women eligible for
      trial of labor after cesarean (TOLAC) delivery in Brazil. METHODS: The present
      data were retrieved from the Birth in Brazil study, a national hospital-based
      cohort study conducted during 2011-2012. Data were collected from medical records
      and by interview. Univariate and hierarchical multiple logistic regression
      analyses were performed to analyze factors associated with ERCD among women with
      a previous cesarean delivery who were eligible for TOLAC. RESULTS: Among 2295
      women considered eligible for TOLAC, 1516 (66.1%) had an ERCD; the overall
      cesarean delivery rate was 79.4%. In the private sector, almost all deliveries
      (95.3%) were performed by ERCD. In the public sector, ERCD was associated with
      socioeconomic (more years of schooling), obstetric (women's preference, no
      previous vaginal delivery, macrosomia), and hospital (mixed hospital, location in
      noncapital city, fewer than 1500 deliveries per year) characteristics.
      CONCLUSION: The ERCD rate in Brazil was high even in a low-risk group, indicating
      that nonclinical factors may be driving the decision for cesarean delivery.
      Efforts aiming to reduce cesarean deliveries in Brazil should target women with a
      previous cesarean delivery.

PMID- 30182482
TI  - The clinical, biochemical, and ultrasonographic characteristics of patients with
      hidradenitis suppurativa in Northern Peninsular Malaysia: a multicenter study.
AB  - BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, recurrent, inflammatory
      disorder of follicular occlusion, resulting in abscesses with tunnel formation
      and severe scarring. Our objectives were to identify the clinical patterns and
      the prevalence of metabolic syndrome (MetS) among our HS patients and to
      determine the role of ultrasonography in the clinical assessment of HS. METHODS:
      This was a cross-sectional study carried out from September 2016 to August 2017
      at three tertiary hospitals in Northern Peninsular Malaysia. RESULTS: A total of
      62 patients were recruited, 83.9% of whom were male. The mean age was 29.2 with
      the median age of onset at 18 years old. The median duration of delay in
      diagnosis was 3 years. A quarter of them had positive family history. Nearly
      three-quarters were overweight and obese. About 12/62 (19.4%) had MetS, and it
      was comparable to healthy controls (15/62, 24.2%). HS patients had a significant
      higher risk of low-high-density lipoprotein (HDL) and obesity. Based on Hurley
      staging, 15/62 (24.2%) were in stage I, 38/62 (61.3%) and 9/62 (14.5%) in stages
      II and III, respectively. However, sonographic scoring showed 50% had severe
      stage of disease, and 56.9% of the patients had subclinical lesions. There was
      only a fair agreement between ultrasonography and Hurley staging of disease
      severity (k = 0.25; P = 0.004). CONCLUSION: There was a male preponderance among
      HS patients in Northern Peninsular Malaysia with early age of onset and more
      severe disease. Only one-fifth had MetS, but they had significantly higher risks
      of obesity and low HDL. Ultrasonography examination was useful to detect
      subclinical lesions and providing a better understanding on disease severity.

PMID- 30182483
TI  - Linking process and effects of intersectoral action on local neighbourhoods:
      systemic modelling based on Actor-Network Theory.
AB  - After 25 years of intersectoral practice to increase health promotion resources,
      there is little scientific literature linking analysis of processes to
      observation of effects. Applying Actor-Network Theory, this article examines how
      the effects of intersectoral action are produced and can be attributed to its
      processes. A prospective multiple case study (2013-2016) was conducted on
      Neighbourhood Committees (NCs) in Montreal (Canada). Three NCs were studied using
      four kinds of data: direct observation notes of meetings and events, documents,
      logbooks and interviews. Systemic modelling of local intersectoral action was
      used for data collection and analysis. The results show that the transformations
      in living environments were produced by sequences of a limited number of
      'transitory outcomes' that mark the progression of intersectoral action up to its
      effects. The list of transitory outcomes identified make up three functions in
      the production of change: (i) network setup and governance; (ii) self
      representing and influencing others; (iii) aligning necessary actors and
      resources. The production of effects follows a systemic model wherein unique
      configurations of transitory outcomes, adapted to the different contexts where
      interactions are occurring, represent the change processes that lead to the
      effects.

PMID- 30182484
TI  - Continuous-flow Suzuki-Miyaura and Mizoroki-Heck Reactions under Microwave
      Heating Conditions.
AB  - Microwave-assisted continuous-flow reactions have attracted significant interest
      from synthetic organic chemists, especially process chemists from practical
      points of view, due to a less complicated shift to large-scale synthesis based on
      simple and continuous access to products with low energy requirements. In this
      personal account, we focused on the Suzuki-Miyaura and Mizoroki-Heck reactions,
      both of which are significantly important cross-coupling reactions for the
      synthesis of various functional materials. Microwave power is effective for
      heating. Typical homogeneous palladium catalysts, such as PdCl2 (PPh3 )2 ,
      Pd(PPh3 )4 , and Pd(OAc)2 , as well as heterogeneous palladium catalysts, such as
      Pd-film, Pd/Al2 O3 , Pd/SiO2 , and Pd supported on polymers, can be used for
      these reactions.

PMID- 30182485
TI  - Baby with the Bathwater? Examining the Relationship between Video Game Use and
      Relationship Outcomes and the Moderating Effects of Attachment Behaviors among
      Married Casual Gamers.
AB  - We examined whether time together as a problem mediates the link between
      frequency of video game use and relational outcomes (relationship quality,
      relational aggression, physical aggression) among 431 married couples. We also
      examined the moderating effect of couple attachment behaviors on the association
      between time together as a problem and outcomes. There was no support for a
      direct or indirect relationship between gaming and outcomes; however, time
      together as a problem was consistently related to outcomes. Additionally,
      husband's and wife's attachment behaviors moderated the association between
      women's reports of time together as a problem and men's relational aggression.
      Clinical implications are discussed.

PMID- 30182486
TI  - Tricuspid annular plane of systolic excursion to prognosticate acute pulmonary
      symptomatic embolism (TAPSEPAPSE study).
AB  - INTRODUCTION: The imaging standard for evaluation of acute pulmonary embolism
      (PE) includes a computed tomography pulmonary angiogram. Ultrasonography has
      shown promise in obtaining the tricuspid annular plane systolic excursion (TAPSE)
      measurements, which may be of clinical importance in patients with acute PE. The
      objective of this study is to evaluate the diagnostic capability of TAPSE
      measurements for patients with suspicion for acute PE. METHODS: We prospectively
      enrolled patients who came to the emergency department with suspicion of acute
      PE. Each patient underwent a point-of-care sonogram where a TAPSE measurement was
      obtained, followed by computed tomography pulmonary angiogram. Based on the
      computed tomography pulmonary angiogram findings, patients were grouped into 3
      categories: no acute PE, clinically insignificant acute PE, or clinically
      significant acute PE. RESULTS: We enrolled 87 patients in this study. Twenty
      three (26.4%) of these patients were diagnosed with PE. Of patients with PE, 15
      (65%) were found to have a clinically significant acute PE. Analysis of mean
      TAPSE measurements between patients with clinically significant acute PE and
      those with insignificant or no PE was 15.2 mm and 22.7 mm, respectively (P <=
      .0001). Following receiver operating characteristic curve analysis, optimum TAPSE
      measurement to identify clinically significant acute PE is 18.2 mm. A cutoff
      TAPSE measurement of 15.2 mm shows a sensitivity of 53.3% (95% confidence
      interval, 26.7%-80%) and a specificity of 100% (95% confidence interval, 100%
      100%) for the diagnosis of a clinically significant PE. CONCLUSIONS: Our data
      suggest that TAPSE measurements less than 15.2 mm have a high specificity for
      identifying clinically significant acute PE.

PMID- 30182487
TI  - Comparing contemporary medical treatment practices aimed at intersex/DSD bodies
      in Israel and Germany.
AB  - Recently, new laws and medical guidelines in many countries have prohibited early
      genital surgeries and irreversible medical treatment for intersexed babies.
      Following the passing of the German law that allows parents to register
      intersexed babies with no sex/gender, and after the establishment of new medical
      guidelines for intersexed patients in Israel, this study aims to examine the
      current medical policies regarding intersexed bodies at DSD centres and hospitals
      in Israel and Germany. How, if at all, have they changed the previous medical
      guidelines? This is a narrative study that includes 62 in-depth interviews with
      medical professionals, parents and intersexed people from Germany and Israel.
      Three main controversial themes are examined, including the situated diagnostic
      medical gaze, the surgical practices for normalising intersexed bodies and the
      concealment of intersexed bodies. I find that in Israeli hospitals, early
      irreversible surgeries for 'ambiguous genitals' and the removal of internal sex
      organs are taking place frequently, whereas in Germany, the three DSD centres
      examined offer psychological counselling for parents instead of early surgeries
      for their babies. While in Israel concealment practices are embodied in the
      medical policy, the DSD centres in Germany encourage openness and peer group
      support.

PMID- 30182488
TI  - The impact of early-stage dementia on community-dwelling care recipient/carer
      dyads' capacity to self-manage.
AB  - AIMS AND OBJECTIVES: To explore the impact of early-stage dementia on care
      recipient/carer dyads' confidence or belief in their capacity to manage the
      behavioural and functional changes associated with dementia and to access
      appropriate support networks. BACKGROUND: Living with dementia has predominantly
      been explored from the carer perspective and focused on the stress and burden of
      supporting a person with dementia. There has been a shift towards a more positive
      discourse to accommodate the role of self-efficacy in supporting self-management
      by people living with dementia. However, little has been reported on the dyadic
      experience of self-efficacy in managing life with dementia. DESIGN: A qualitative
      study using an interpretive descriptive approach. Semi-structured interviews were
      conducted with 13 dyads in the early stages of dementia. The collected data
      underwent a process of thematic analysis. The study followed the COnsolidated
      criteria for REporting Qualitative research (COREQ) checklist. RESULTS: Dyadic
      adjustment to dementia was dynamic, involving shifts between loss and adaptation.
      Threats to self-efficacy, declining autonomy and stigma, were significant causes
      of concern for both members of the dyad. Dyadic self-efficacy was demonstrated
      through recognition of and adaptation to dementia-related changes and development
      of coping strategies to integrate impairment into everyday life. CONCLUSIONS:
      Solution-focused approaches that improve knowledge and skills enable the dyad to
      adjust. The considerable impact of stigma on self-efficacy indicates that
      supportive disclosure strategies developed in mental health may also have a role
      to play in dementia interventions. RELEVANCE TO CLINICAL PRACTICE: Nurses play a
      significant role in advising and supporting care recipient/carer dyads with
      dementia, and a better understanding of the dyadic perspective provides them with
      essential information to support self-management. A proactive approach including
      information and support, offered at the beginning of the condition/care
      trajectory, may have the potential to delay progression into more dependent
      stages.

PMID- 30182489
TI  - Predicting venous congestion before DIEP breast reconstruction by identifying
      atypical venous connections on preoperative CTA imaging.
AB  - BACKGROUND: Venous congestion is the principle cause of flap failure after
      microsurgical breast reconstruction. We aim to correlate preoperative computed
      tomography angiography (CTA) findings with postoperative venous congestion to
      predict patients at risk of congestion. METHODS: All patients undergoing deep
      inferior epigastric perforator (DIEP) breast reconstruction between August 2009
      and August 2013 underwent preoperative CTA and prospectively entered the study.
      Patients with postoperative venous congestion were matched with a similar cohort
      of complication-free patients. Preoperative CTAs were randomized and re
      interpreted by a radiologist, blinded to the subsequent clinical outcome. Inter
      group comparisons were performed. RESULTS: Two hundred and forty DIEP flaps were
      performed in 202 patients over the 4-year study. Venous congestion affected 15
      flaps (6.3%). Preoperative CTA showed significantly more atypical venous
      connections between deep and superficial systems in congested flaps compared to
      controls (66.7% vs. 8%; P < .0001), with a positive predictive value of 83%.
      Atypical connections were narrow, tortuous, or incomplete. Patients with
      congestion-free flaps had more normal connections (80% vs. 26.7%; P < .001) and
      more cranial perforators (P = .02). Similar CTA findings between groups included
      perforator size and lateral position, superficial inferior epigastric vein size,
      crossing of midline, and absent connections (P > .05). CONCLUSIONS: Preoperative
      CTA identifies atypical venous connections between deep and superficial systems
      that increase the risk of postoperative DIEP congestion five-fold. Identifying
      atypical venous connections maximizes the chances of flap survival and minimizes
      complications for patients considering DIEP breast reconstruction.

PMID- 30182491
TI  - September 2018 at a glance: co-morbidities, heart failure with preserved ejection
      fraction and mineralocorticoid receptor antagonists.

PMID- 30182490
TI  - Computed tomography or contrast-enhanced ultrasonography for follow-up of liver
      metastases after Cyberknife therapy?: A prospective pilot study.
AB  - OBJECTIVES: Contrast-enhanced ultrasonography (CEUS) allows the study of
      vascularization of secondary liver lesions. The Cyberknife (Accuray, Inc,
      Sunnyvale, CA) is a therapeutic method that allows a tumor target to be subjected
      to a high radiant dose gradient. This prospective pilot study aimed to
      demonstrate the concordance of CEUS versus contrast-enhanced computed tomography
      (CECT) in determining the stability or disease progression of secondary liver
      lesions after treatment with the Cyberknife. METHODS: Twenty-four patients were
      consecutively enrolled, and 3 different operators evaluated the CEUS images and
      the intermodality concordance with CECT. All patients received CEUS at 1 and 2
      months after the Cyberknife therapy. The intermodality agreement was evaluated by
      the Cohen kappa coefficient and a multivariate analysis according to the method
      of Janson and Olsson (Educ Psychol Meas 2001; 61:277-289). RESULTS: Forty
      secondary liver lesions were detected and treated. Forty-one CECT and 51 CEUS
      examinations were performed without any adverse events in the 24 patients. The
      intermodality agreement rates, calculated for the operators as Cohen kappa
      values, were kappa = 1.00, 0.881, and 0.767, respectively. The multivariate
      analysis of intermodality agreement showed an almost perfect value (iota =
      0.841). CONCLUSIONS: This pilot study found excellent diagnostic correspondence
      between CEUS and CECT in the evaluation of local disease stability or progression
      after Cyberknife therapy in liver metastases. These findings suggest that CEUS
      could play an important role in the surveillance of these patients because of its
      high accuracy and reproducibility, thus reducing the need for CECT.

PMID- 30182492
TI  - No urgent need for revisiting kalaemia guidelines: rebuttal.

PMID- 30182493
TI  - Revisiting hyperkalaemia guidelines: rebuttal.

PMID- 30182494
TI  - Innovation for hepatotoxicity in vitro research models: A review.
AB  - Many categories of drugs can induce hepatotoxicity, so improving the prediction
      of toxic drugs is important. In vitro models using human hepatocytes are more
      accurate than in vivo animal models. Good in vitro models require an abundance of
      metabolic enzyme activities and normal cellular polarity. However, none of the in
      vitro models can completely simulate hepatocytes in the human body. There are two
      ways to overcome this limitation: enhancing the metabolic function of hepatocytes
      and changing the cultural environment. In this review, we summarize the current
      state of research, including the main characteristics of in vitro models and
      their limitations, as well as improved technology and developmental prospects. We
      hope that this review provides some new ideas for hepatotoxicity research.

PMID- 30182495
TI  - Aesthetic dermatology: What's new, what's true?
AB  - Aesthetic dermatology (AD) is a rapidly growing subspecialty of dermatology. The
      acceptance of AD in scientific community and the society is associated with its
      competence, efficiency, and seriousness. This review highlights some recent
      developments toward new tools, techniques, and understanding in the field of AD.
      Analyzing the specific needs of patients and assessing the effect by objective
      measurements is important for further progress. For long time ignored, white
      adipose tissue has gained increasing interest in biology and rejuvenation.
      Characterization of dermal and subcutaneous white adipose tissue has made
      progress. The interaction of hyaluronic acid and calcium hydroxyl apatite (CaHA)
      fillers with adipocytes could be responsible for clinical efficacy. New
      developments of oral collagen treatment and highly diluted CaHA to contour the
      body outside the face will be discussed. Submental contouring using purified
      desoxycholic acid is another new development.

PMID- 30182496
TI  - S100A11 promotes cell proliferation via P38/MAPK signaling pathway in
      intrahepatic cholangiocarcinoma.
AB  - S100A11 is reported to associate with progression and poor prognosis in several
      tumors. We previously reported that S100A11 was highly expressed in intrahepatic
      cholangiocarcinoma (ICC) cells and promoted TGF-beta1-induced EMT through SMAD2/3
      signaling pathway. Here, we explored the prognostic role of S100A11 on ICC
      patients and preliminary molecular mechanisms how S100A11 regulated ICC cell
      proliferation. Our results showed that S100A11 was obviously increased in ICC
      tumor tissues. High expression of S100A11 was closely correlated with lymph node
      metastasis (LNM) and TNM stage and was an independent risk factor for patients'
      overall survival (OS) and recurrence-free survival (RFS). The nomograms
      comprising LNM and S100A11 achieved better predictive accuracy compared with TNM
      staging system for OS and RFS prediction. Silencing S100A11 significantly
      suppressed RBE cells and HCCC9810 cells proliferation, colony formation, and
      activation of P38/mitogen-activated protein kinase (MAPK) signaling pathway in
      vitro and inhibited tumor growth in vivo. In contrast, the overexpression of
      S100A11 in RBE cells and HCCC9810 cells achieved the opposite results. S100A11
      induced proliferation was abolished after treatment with P38 inhibitor. Our
      findings suggest S100A11/P38/MAPK signaling pathway may be a potential
      therapeutic target for ICC patients.

PMID- 30182497
TI  - Inter-rater agreement in the diagnosis of adenomyosis by 2- and 3-dimensional
      transvaginal ultrasonography.
AB  - OBJECTIVES: To assess the inter-rater agreement of 2-dimensional (2D) and 3
      dimensional (3D) transvaginal ultrasonography (TVUS) in the diagnosis of
      adenomyosis. METHODS: This prospective study included premenopausal women (n =
      96) with heavy menstrual bleeding, menstrual pain, or both who were scheduled for
      hysterectomy or transcervical resection of the endometrium. All women underwent
      real-time 2D TVUS and subsequently offline 3D TVUS, which was blinded to 2D TVUS,
      by a single expert rater and a single nonexpert rater for the diagnosis of
      adenomyosis based on standardized pattern recognition and junctional zone
      measurements. Three-dimensional TVUS was done on a computer with 3D volumes
      recorded during 2D TVUS by both raters. The expert rater reported the image
      quality of all 3D volumes (n = 192). Inter-rater agreement (Cohen's kappa) was
      assessed for both techniques, and the improvement over time was assessed for 2D
      TVUS. RESULTS: Diagnosis of adenomyosis showed good (kappa = 0.69) and poor
      (kappa = 0.21) inter-rater agreement with 2D and 3D TVUS, respectively (P < .05).
      The agreement with 2D TVUS improved over time. The agreement with 3D TVUS was
      slightly better for expert-recorded 3D volumes (kappa = 0.40), which also had
      better image quality (P < .05). The most reproducible 2D and 3D features were
      anechoic lacunae (kappa = 0.52) and junctional zone irregularity (kappa = 0.27),
      respectively. CONCLUSIONS: Standardized pattern recognition during real-time 2D
      TVUS may result in good agreement between expert and nonexpert raters for the
      diagnosis of adenomyosis. Offline 3D TVUS is less reproducible, and junctional
      zone measurements do not improve the inter-rater agreement. The low inter-rater
      agreement may be related to a lack of experience and low image quality of
      nonexpert-recorded 3D volumes.

PMID- 30182498
TI  - Genotype and phenotype analysis using an epilepsy-associated gene panel in
      Chinese pediatric epilepsy patients.
AB  - Epilepsy is a common and genetically heterogeneous disorder among children.
      Advances in next-generation sequencing have revealed that numerous epilepsy
      genes, helped us improve the understanding of mechanisms underlying
      epileptogenesis, and guided the development of treatments. We identified 39
      candidate variants in 21 genes, including 37 that were pathogenic or likely
      pathogenic variants according to the American College of Medical Genetics and
      Genomics scoring system and two variants of uncertain significance that were
      considered causative after they were associated with clinical characteristics.
      Thirty were de novo variants (76.9%), and 20 variants had not previously been
      reported (51.3%). We obtained a diagnosis in 39 of the 141 probands (27.7%). The
      most frequently mutated gene was SCN1A; KCNQ2, KCNT1, PCDH19, STXBP1, SCN2A,
      TSC2, and PRRT2 were mutated in more than one individual; ANKRD11, CDKL5, DCX,
      DEPDC5, GABRB3, GRIN2A, IQSEC2, KCNA2, KCNB1, KCNJ6, TSC1, SCN9A, and SCN1B were
      mutated in a single individual. In addition, we detected a nonsense variant in a
      candidate gene KCND1 and considered it as a new candidate epilepsy gene, which
      needed further functional study. Consequently, large number of unreported
      variants were detected, diverse phenotypes were associated with known epilepsy
      genes. Changes in clinical management beyond genetic counseling were suggested.

PMID- 30182499
TI  - Deep inferior epigastric lymph node basin: Analysis of novel donor site for
      vascularized lymph node transfer among 10 consecutive patients.
AB  - INTRODUCTION: Breast cancer-related extremity lymphedema is a potentially
      devastating condition. Vascularized lymph node transfer (VLNT) has shown benefit
      in lymphedema treatment. Due to concerns over potential iatrogenic complications,
      various donor sites have been described. The current study aims at defining the
      deep inferior epigastric lymph node basin as a novel donor site for VLNT.
      METHODS: A retrospective study was performed on patients undergoing routine
      abdominal-based breast reconstruction. Resection of all perivascular adipose and
      lymphatic tissue surrounding the proximal deep inferior epigastric pedicle was
      performed at the time of pedicle dissection and submitted for Pathologic
      evaluation. Patient demographics and pertinent medical/surgical history was
      obtained from medical records. RESULTS: Specimens were obtained from 10
      consecutive patients. Seven patients underwent bilateral reconstruction for a
      total of 17 specimens obtained. Mean patient age and BMI were 48 years +/- 9.4
      and 27 +/- 4.2, respectively. Fourteen out of 17 (82%) specimens contained viable
      lymph nodes displaying a thin fibrous connective tissue capsule overlying an
      unremarkable subcapsular sinus with a cortex and paracortex containing germinal
      centers composed of B lymphocytes, tangible body macrophages, and T-cells. The
      medullary sinus space displayed a fatty unremarkable hilum. The mean number and
      size of lymph nodes were 2.6 +/-1.2 nodes/specimen and 3.67 mm +/- 2.3,
      respectively. All patients experienced an uneventful postoperative course without
      evidence any of compromised flap viability. CONCLUSION: Lacking previous
      description, the deep inferior epigastric lymph node basin is a readily
      accessible donor site with significant anatomic advantages for potential VLNT
      during autologous breast reconstruction.

PMID- 30182500
TI  - Embracing scale-dependence to achieve a deeper understanding of biodiversity and
      its change across communities.
AB  - Because biodiversity is multidimensional and scale-dependent, it is challenging
      to estimate its change. However, it is unclear (1) how much scale-dependence
      matters for empirical studies, and (2) if it does matter, how exactly we should
      quantify biodiversity change. To address the first question, we analysed studies
      with comparisons among multiple assemblages, and found that rarefaction curves
      frequently crossed, implying reversals in the ranking of species richness across
      spatial scales. Moreover, the most frequently measured aspect of diversity -
      species richness - was poorly correlated with other measures of diversity.
      Second, we collated studies that included spatial scale in their estimates of
      biodiversity change in response to ecological drivers and found frequent and
      strong scale-dependence, including nearly 10% of studies which showed that
      biodiversity changes switched directions across scales. Having established the
      complexity of empirical biodiversity comparisons, we describe a synthesis of
      methods based on rarefaction curves that allow more explicit analyses of spatial
      and sampling effects on biodiversity comparisons. We use a case study of nutrient
      additions in experimental ponds to illustrate how this multi-dimensional and
      multi-scale perspective informs the responses of biodiversity to ecological
      drivers.

PMID- 30182501
TI  - Tetranuclear Dysprosium(III) Quintuple-Decker Single-Molecule Magnet Prepared
      Using a pi-Extended Phthalocyaninato Ligand with Two Coordination Sites.
AB  - The magnetic properties and spin relaxation processes of a tetranuclear
      dysprosium(III) fused phthalocyaninato (Pc4- ) quintuple-decker single-molecule
      magnet (SMM) (1) with non-equivalent octa-coordination geometries are reported.
      The structure of 1 is regarded as a dimer of Dy3+ -Pc triple-decker SMMs with
      different magnetic relaxation characteristics, corresponding to the octa
      coordination geometry sites Dy1 with C4 symmetry (phi1 =23 degrees ) and Dy2 with
      D4d symmetry (phi2 =45 degrees ). In an Hdc of 1750 Oe and T range of 1.8-3.75 K,
      the quantum tunnelling of the magnetization was suppressed, and the direct
      process was enhanced. The effects of the coordination geometry on the spin
      relaxation phenomena are examined.

PMID- 30182502
TI  - A nurse-led FibroScan(r) outreach clinic encourages socially deprived heavy
      drinkers to engage with liver services.
AB  - AIMS AND OBJECTIVES: To determine whether a portable FibroScan(r) device can be
      an acceptable screening tool for chronic liver disease in a community alcohol
      support service, through recording uptake, determining apparent prevalence of
      undiagnosed fibrosis/cirrhosis in participants and report engagement following
      referral to specialist liver services of those individuals referred because of a
      FibroScan(r) reading >= 7.1 kilopascals (kPa). BACKGROUND: Alcohol-related liver
      disease, including cirrhosis, is a major cause of death in the UK. Liver disease
      is silent and usually presents late. Socially deprived patients with alcohol
      related liver disease are a "hard to engage" population and at higher risk of
      death than less deprived. A FibroScan(r) device is a non-invasive tool for
      measuring liver stiffness. A result of >=7.1 kPa can indicate possible chronic
      liver disease. DESIGN: Prospective observational study. METHOD: Individuals who
      self-identified as harmful drinkers were recruited. Consented individuals
      attended for a liver FibroScan(r) . Those with a reading >=7.1 kPa were referred
      to a nurse-led liver clinic for further investigations, results of which
      determined referral to a liver specialist in secondary care. Participants
      referred were monitored for compliance over a 6-month period. RESULTS: Seventy
      nine consented individuals participated, an uptake of 67% of those informed of
      the study. Of the 79 scans performed, three were unreliable leaving 76
      participants. After scanning, 20/76 (26%) had a FibroScan(r) >=7.1 kPa requiring
      referral on to the nurse-led clinic. All 20 (100%) engaged in further assessment.
      Of those, 12 required onward referral to specialist services. Subsequent
      compliance with specialist services in this sample (n = 12) was >=90%.
      CONCLUSION: A nurse-led FibroScan(r) outreach clinic encourages socially deprived
      drinkers to engage with liver services. RELEVANCE TO CLINICAL PRACTICE: A 67%
      uptake suggests a nurse-led FibroScan(r) service in a community alcohol service
      is acceptable. High engagement gives potential for early intervention and
      improved health outcomes.

PMID- 30182503
TI  - Determination of three phenylethanoid glycosides in Osmanthus fragrans fruits by
      high-performance liquid chromatography with fluorescence detection.
AB  - A simple and sensitive high-performance liquid chromatography with fluorescence
      detection method has been developed for the determination of active components in
      Osmanthus fragrans fruits. In this work, reversed-phase liquid chromatography
      with a C18 column and mobile phase of methanol/water were applied to effectively
      separate three phenylethanoid glycosides, including salidroside, neonuezhenide,
      and nuezhenide. The limits of detection of salidroside, neonuezhenide, and
      nuezhenide were 3.9, 25.4, and 24.2 ng/mL respectively. Then this method was
      applied to determine the contents in several batches of O. fragrans fruits
      extract, which were collected from Wuhan, Hefei, and Changsha. Meanwhile, the
      method was used for the detection of rat plasma administrated with O. fragrans
      fruits extract, which could be an alternative method applied to the field of
      pharmacokinetics study in future. The results implied that the developed method
      was economical, simple, convenient, and sensitive, which was appropriate for the
      determination of salidroside, neonuezhenide, and nuezhenide in O. fragrans
      fruits.

PMID- 30182504
TI  - Brood-tending males in a biparental fish suffer high paternity losses but rarely
      cuckold.
AB  - Extra-pair paternity within socially monogamous mating systems is well studied in
      birds and mammals but rather neglected in other animal taxa. In fishes, social
      monogamy has evolved several times but few studies have investigated the extent
      to which pair-bonded male fish lose fertilizations to cuckolders and gain extra
      pair fertilizations themselves. We address this gap and present genetic paternity
      data collected from a wild population of Variabilichromis moorii, a socially
      monogamous African cichlid with biparental care of offspring. We show that brood
      tending, pair-bonded males suffer exceptionally high paternity losses, siring
      only 63% of the offspring produced by their female partners on average. The
      number of cuckolders per brood ranged up to nine and yet, surprisingly, brood
      tending males in the population were rarely the culprits. Brood-tending males
      sired very few extra-pair offspring, despite breeding in close proximity to one
      another. While unpaired males were largely responsible for the cuckoldry, pair
      bonded males still enjoyed higher fertilization success than individual unpaired
      males. We discuss these results in the context of ecological and phenotypic
      constraints on cuckoldry and the fitness payoffs of alternative male tactics. Our
      study provides new insights into how pair-bonded males handle the trade-off
      between securing within-pair and extra-pair reproduction.

PMID- 30182505
TI  - The hidden patient: chronic physical morbidity, psychological distress, and
      quality of life in caregivers of older adults.
AB  - AIM: Increasing demands for care provision to older adults require good physical
      and mental health among caregivers. Few studies have examined the health status
      and correlates of quality of life among caregivers of older adults. The present
      study therefore sought to examine the prevalence of chronic physical conditions,
      psychological distress, and correlates of physical and mental quality of life
      among caregivers of older adults (>=60 years) in Singapore. METHODS: Participants
      were 285 informal caregivers who were providing care to an older relative.
      Participants were recruited at the Institute of Mental Health, Singapore, and
      they completed self-report measures on chronic physical morbidity, psychological
      distress, and physical and mental quality of life. Multiple regression models
      were constructed to examine correlates of physical and mental quality of life.
      RESULTS: More than half of the caregivers had at least one chronic physical
      condition (58.6%) and psychological distress (52.6%). Chronic physical morbidity,
      psychological distress, and secondary education status were associated with lower
      physical quality of life. Psychological distress, younger age, primary education
      status, and more time spent caregiving were associated with lower mental quality
      of life. CONCLUSION: Poor physical and mental health among caregivers may impair
      their ability to provide adequate care to older adults with progressive medical
      needs. It is important for medical practitioners not to neglect the physical and
      mental health of caregivers through continued assessment of chronic physical
      morbidity, psychological distress, and quality of life.

PMID- 30182506
TI  - Evaluation of subclinical atherosclerosis using ultrasound radiofrequency data
      technology in patients diagnosed with ankylosing spondylitis.
AB  - OBJECTIVE: The present study aims to identify the cardiovascular risk associated
      with chronic inflammation and disease activity in patients with ankylosing
      spondylitis (AS) using noninvasive ultrasonographic radiofrequency data
      technology. METHODS: In this study, a total of 87 participants, 38 patients with
      AS and 49 healthy controls, were evaluated by Doppler ultrasonography. Intima
      media thickness (IMT) and arterial stiffness were measured from the bilateral
      common carotid artery using the radiofrequency method. RESULTS: No statistically
      significant difference was found between the AS patients and healthy controls
      concerning the right common carotid artery, left common carotid artery, IMT,
      distensibility coefficient, elasticity coefficient, alpha and beta stiffness
      indexes, and pulse wave velocities (P > .05). The symptom duration of the AS
      patients had a positive correlation that was moderate and was detected with the
      alpha stiffness index and pulse wave velocity (P < .05). The duration of
      diagnosis and treatment of the AS patients had a positive correlation that was
      moderate, was detected with the alpha stiffness index, the beta stiffness index,
      and pulse wave velocity (P < .05). The mean IMT and elasticity coefficient values
      of the AS patients whose Bath Ankylosing Spondylitis Disease Activity Index score
      was 4 and above, were substantially higher than the values in the patients with
      scores lower than 4 (P = .038 and P = .33, respectively). CONCLUSIONS:
      Subclinical atherosclerosis is not accelerated in AS patients with low disease
      activity, although insufficiently controlled disease activity may result in
      increased carotid IMT and atheromatosis. Radiofrequency data technology provides
      a noninvasive method for accurately and quantitatively demonstrating CCA-IMT
      elevation and the decrease in vascular elasticity in patients with AS.

PMID- 30182507
TI  - Illegitimate authorship and flawed procedures: Fundamental, formal criticisms of
      the Declaration of Helsinki.
AB  - Some of the recent criticisms published during and after the last revision
      process of the Declaration of Helsinki are directed at its basic legitimacy. In
      this article we want to have a closer look at the two criticisms we consider to
      be the most fundamental. The first criticism questions the legitimate authorship
      of the World Medical Association to publish a document such as the Declaration.
      The second fundamental criticism we want to examine argues that the last revision
      process failed to meet the standards for fair, democratic procedures. Although
      both criticisms deny the formal legitimacy of the Declaration in the most
      fundamental way, they have never been addressed in detail in a single article. We
      refute most of the related arguments. However, acknowledging some of the points
      made, improvements for future revision processes and versions of the Declaration
      of Helsinki are outlined.

PMID- 30182508
TI  - Editorial Comment from Dr Kuroda to Differences in semen characteristics between
      patients with testicular cancer and other malignancies using various cut-off
      values.

PMID- 30182509
TI  - Editorial Comment to Renal tumors in end-stage renal disease: A comprehensive
      review.

PMID- 30182511
TI  - Closure of the perineal defect after abdominoperineal excision for rectal
      adenocarcinoma - ACPGBI Position Statement.
AB  - BACKGROUND: Perineal wound morbidity is common following abdominoperineal
      excision of the rectum (APE). There is no consensus on the optimum perineal
      reconstruction method after APE, and in particular 'extra-levator APE' (ELAPE).
      METHODS: A systematic review of the PubMed, Embase and Cochrane databases was
      performed. This position statement formulated clinical questions and graded the
      evidence to make recommendations. RESULTS: Perineal wound complications may be
      higher following ELAPE compared to 'conventional APE (cAPE)' however there is
      insufficient evidence to recommend cAPE over ELAPE with regards to the impact
      upon perineal wound healing. The majority of cAPE studies have used primary
      closure with varying complication rates reported. Where concerns regarding
      perineal wound healing exist, myocutaneous flap closure may be considered as an
      alternative method. There is minimal available evidence on perineal mesh
      reconstruction following cAPE. Primary closure, mesh use and myocutaneous flap
      reconstruction following ELAPE has been reported although variations in
      definitions and low-quality of available evidence limit comparison. There is
      insufficient evidence to recommend one particular method of perineal closure
      after ELAPE. Primary perineal closure is likely to have a higher risk of perineal
      herniation. Myocutaneous flaps and biological mesh have been effectively used in
      ELAPE closure. There is insufficient evidence to support one particular type of
      flap or mesh. Perineal wound complication rates are significantly increased when
      neo-adjuvant radiotherapy is delivered, regardless of surgical technique. There
      is no evidence that laparoscopy reduces APE perineal wound complications.
      CONCLUSION: This position statement updates clinicians on current evidence around
      perineal closure after APE surgery.

PMID- 30182512
TI  - Design and Catalytic Application of Functional Porous Organic Polymers:
      Opportunities and Challenges.
AB  - This review article encompasses the progress and conventional overview of current
      research activities of porous organic polymers (POPs), especially in catalysis,
      as they have garnered colossal interest in the scientific fraternity due to their
      intriguing characteristic features. Various synthetic strategies with possible
      modification of functionality of POPs have been used to improve the catalytic
      efficiency towards value-added chemicals production. Accordingly, this review
      article is mainly focused on the design, development of various functionalized
      POPs by employing Friedel-Crafts alkylation, FeCl3 assisted oxidative
      polymerisation and polymerisation in nonaqueous medium, and a comprehensive
      understanding in potential catalytic applications namely, acetalization,
      hydrodeoxygenation (HDO), hydrogenation, coupling, photocatalytic hydrogen
      evolution and biomass conversion towards the production of value-added chemicals
      in biodiesel and chemical industries.

PMID- 30182513
TI  - Folate, vitamin B12, and homocysteine in smoking-exposed pregnant women: A
      systematic review.
AB  - Smoking exposure is associated with pregnancy complications, as are levels of
      folate, vitamin B12, and homocysteine. In nonpregnant adults, smoking exposure is
      associated negatively with folate and vitamin B12 levels and positively with
      homocysteine levels. A complete overview of the literature on this topic in
      pregnant women is lacking. To evaluate evidence of associations of maternal
      smoking exposure during pregnancy and levels of folate, homocysteine, and vitamin
      B12 in pregnancy and in cord blood, we searched MEDLINE, Embase, CINAHL,
      Cochrane, Scopus, Web of Science, and reference lists of relevant studies until
      August 2017. We selected studies in pregnant women describing the association of
      passive or active smoking and levels of folate, homocysteine, and/or vitamin B12.
      Data were extracted by two independent reviewers. We included 32 studies of 2,015
      identified references with a total of 37,822 participants and more than 6,000
      smokers. Twenty-eight studies measured folate, 14 measured vitamin B12, and 13
      measured homocysteine. Nineteen out of 28 studies assessing folate reported
      significantly lower levels in pregnant women exposed to smoking compared with
      those unexposed. Vitamin B12 levels were lower in smoking mothers in eight out of
      14 studies. Homocysteine levels tended to be higher in mothers exposed to
      smoking. Smoking exposure during pregnancy is generally associated with lower
      folate and vitamin B12 levels and higher homocysteine levels. This may help raise
      further awareness about the consequences of smoking and the need to encourage
      stopping smoking in all, especially in pregnant women.

PMID- 30182514
TI  - Current status and influencing factors of barriers to enteral feeding of
      critically ill patients: A multicenter study.
AB  - AIMS AND OBJECTIVES: To investigate the barriers in administering enteral feeding
      to critically ill patients from the nursing perspective. Our objectives are to
      provide tailored interventions for addressing identified barriers and propose an
      optimal enteral nutrition (EN) practice in intensive care unit (ICU). BACKGROUND:
      Despite the availability of numerous verified clinical practice guidelines
      focusing on enteral feeding of critically ill patients, a wide gap remains
      between the guideline recommendations and actual nutrition performances.
      Underfeeding is also a global problem. Therefore, to further understand the
      reasons of the systemic iatrogenic underfeeding in ICUs, several potential issues
      are investigated. DESIGN: This research is a cross-sectional descriptive study.
      METHODS: A total of 808 nurses were recruited from 10 comprehensive hospitals
      from different districts in China. The nursing staff demographic, the unit's EN
      management information and the Chinese version of barriers to enteral feeding
      critically ill patients questionnaire were the parameters used to collect data
      via WeChat app. Moreover, the collected data were analysed by descriptive and
      correlative statistical analysis methods. RESULTS: Results obtained by multiple
      linear regression showed that frequency of EN-related training, full-time ICU
      nutritionist, hospital level, specific protocols for enteral feeding and position
      were significantly influencing the enteral feeding of ICU patients. CONCLUSIONS:
      Enteral feeding barriers of ICU patients are at a moderate level and are
      influenced by multiple aspects. Hence, hospital departments should strengthen
      standardisation and systematic EN training, provide ICU full-time nutritionists
      and distribute medical resources and personnel rationally. Moreover, construction
      of a localised feeding process and exerting subjective initiative of clinical
      nurses from an evidence-based guideline are important. Multifaceted tailored
      interventions should be implemented to address these barriers. RELEVANCE TO
      CLINICAL PRACTICE: The findings of this study can be used to inform future
      intervention and guidelines aimed at addressing these barriers systematically and
      improving adherence to critical care nutrition guidelines for the provision of
      enteral nutrition.

PMID- 30182515
TI  - Family caregivers: Important but often poorly understood.

PMID- 30182516
TI  - A genetic risk score and number of myopic parents independently predict myopia.
AB  - PURPOSE: To investigate whether a genetic risk score (GRS) improved performance
      of predicting refractive error compared to knowing a child's number of myopic
      parents (NMP) alone. METHODS: This was a retrospective analysis of data from the
      Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort study.
      Refractive error was assessed longitudinally between age 7-15 using non
      cycloplegic autorefraction. Genetic variants (n = 149) associated with refractive
      error from a Consortium for Refractive Error And Myopia (CREAM) genome-wide
      association study were used to calculate a GRS for each child. Using refractive
      error at ages 7 and 15 years as the outcome variable, coefficient of
      determination (R2 ) values were calculated via linear regression models for the
      predictors: NMP, GRS and a combined model. RESULTS: Number of myopic parents was
      weakly predictive of refractive error in children aged 7 years, R2  = 3.0% (95%
      CI 1.8-4.1%, p < 0.0001) and aged 15 years, R2  = 4.8% (3.1-6.5%, p < 0.0001).
      The GRS was also weakly predictive; age 7 years, R2  = 1.1% (0.4-1.9%, p <
      0.0001) and 15 years R2  = 2.6% (1.3-3.9%, p < 0.0001). Combining the 2 variables
      gave larger R2 values at age 7, R2  = 3.7% (2.5-5.0%, p < 0.0001) and 15, R2  =
      7.0% (5.0-9.0%, p < 0.0001). The combined model improved performance at both ages
      (both p < 0.0001). CONCLUSION: A GRS improved the ability to detect children at
      risk of myopia independently of knowing the NMP. We speculate this may be because
      NMP captures information concerning environmental risk factors for myopia.
      Nevertheless, further gains are required to make such predictive tests worthwhile
      in the clinical environment.

PMID- 30182517
TI  - Designing interoperable health information systems using Enterprise Architecture
      approach in resource-limited countries: A literature review.
AB  - BACKGROUND: Enterprise Architecture (EA) integrates business and technical
      processes in health information systems (HIS). Low-income and middle-income
      countries (LMIC) use EA to combine management components with disease tracking
      and health care service monitoring. Using an EA approach differs by country,
      addressing specific needs. METHODS: Articles in this review referenced EA, were
      peer-reviewed or gray literature reports published in 2010 to 2016 in English,
      and were identified using PubMed, Scopus, Web of Science, and Google Scholar.
      RESULTS: Fourteen articles described EA use in LMICs. India, Sierra Leone, South
      Africa, Mozambique, and Rwanda reported building the system to meet country needs
      and implement a cohesive HIS framework. Jordan and Taiwan focused on specific HIS
      aspects, ie, disease surveillance and electronic medical records. Five studies
      informed the context. The Millennium Villages Project employed a "uniform but
      contextualized" approach to guide systems in 10 countries; Malaysia, Indonesia,
      and Tanzania used interviews and mapping of existing components to improve HIS,
      and Namibia used of Activity Theory to identify technology-associated activities
      to better understand EA frameworks. South Africa, Burundi, Kenya, and Democratic
      Republic of Congo used EA to move from paper-based to electronic systems.
      CONCLUSIONS: Four themes emerged: the importance of multiple sectors and data
      sources, the need for interoperability, the ability to incorporate system
      flexibility, and the desirability of open group models, data standards, and
      software. Themes mapped to EA frameworks and operational components and to health
      system building blocks and goals. Most articles focused on processes rather than
      outcomes, as countries are engaged in implementation.

PMID- 30182518
TI  - Analytical feasibility of a solvent-assisted flavour evaporation method for aroma
      analyses in bread crumb.
AB  - The analysis of bread aroma is essential in order to evaluate its quality as well
      as to improve it. The use of different methodologies for the analysis of volatile
      compounds lead to varying results. In the present study, the matrix effect,
      extraction efficiency, limits of detection and quantification as well as the
      precision of a proposed solvent-assisted flavour evaporation methodology were
      evaluated for the first time and compared with a reference method, both differing
      in the distillation step. The repeatability (<8%) and matrix effect (present in
      15 of the 31 compounds) were improved with the proposed method but the extraction
      efficiencies (average of 52%) and the intermediate precision (>15%) were not as
      required. However, the applicability of the reference method was limited to
      breads with fat levels <2%. For breads higher in fat, the proposed method
      represents an alternative for aroma analysis.

PMID- 30182519
TI  - Reply.

PMID- 30182520
TI  - MicroRNA Expression Analysis of Human Skin Fibroblasts Treated with High-Fluence
      LED Red Light.
AB  - Skin fibrosis is a chronic debilitating feature of several skin diseases that
      lead to characteristic increases in dermal fibroblast proliferation and collagen
      deposition through upregulation in components of the transforming growth factor
      beta (TGF-B)/SMAD pathway. In contrast to ultraviolet phototherapy, high-fluence
      light-emitting diode-generated red light (HF-LED-RL, 633 nm +/- 15 nm) is a safe,
      economic, and non-invasive therapy with in vitro evidence that supports
      modulation of the key cellular characteristics involved in the pathogenesis of
      skin fibrosis. Limited data exists pertaining to the effects of HF-LED-RL on
      human skin fibroblast microRNA (miRNA). Herein, we explored the effects of HF-LED
      RL on fibroblast miRNA levels using RNA-seq and miRNA expression analysis. Using
      RNA-seq analysis we found that HF-LED-RL at 320 and 640 J/cm2 increased
      transcription of key miRNA that are involved in skin fibrosis including miRNA-29,
      miRNA-196a, and Let-7a, and decreased transcription of miRNA-21, miRNA-23b, miRNA
      31. These microRNA findings provide insight into the molecular underpinnings of
      HF-LED-RL and highlight potential therapeutic targets of interest for the
      treatment of skin fibrosis. Additional research on the specific molecular
      mechanisms underlying HF-LED-RL effects on fibroblasts may provide further
      mechanistic insight into this therapy and may reveal additional future
      therapeutic targets for skin fibrosis. This article is protected by copyright.
      All rights reserved.

PMID- 30182521
TI  - Super-resolution Geometric Barcoding for Multiplexed miRNA Profiling.
AB  - MicroRNA (miRNA) expression profiles hold promise as biomarkers for diagnostics
      and prognosis of complex diseases. Herein, we report a super-resolution
      fluorescence imaging-based digital profiling method for specific, sensitive, and
      multiplexed detection of miRNAs. In particular, we applied the DNA-PAINT (point
      accumulation for imaging in nanoscale topography) method to implement a super
      resolution geometric barcoding scheme for multiplexed single-molecule miRNA
      capture and digital counting. Using synthetic DNA nanostructures as a
      programmable miRNA capture nano-array, we demonstrated high-specificity (single
      nucleotide mismatch discrimination), multiplexed (8-plex, 2 panels), and
      sensitive measurements on synthetic miRNA samples, as well as applied one 8-plex
      panel to measure endogenous miRNAs levels in total RNA extract from HeLa cells.

PMID- 30182522
TI  - Different Degrees of Electron Delocalization in Mixed Valence Ru-Ru-Ru Compounds
      by Cyanido-/Isocyanido-Bridge Isomerism.
AB  - The two stable pairs of trimetallic compounds trans-[Cp*(dppe)Ru(MU-NC)Ru(dmap)4
      (MU-CN)Ru(dppe)Cp*][PF6 ]n (1[PF6 ]n , n=2, 3; Cp*=1,2,3,4,5
      pentamethylcyclopentadiene; dppe=1,2-bis-(diphenylphosphino)ethane; dmap= 4
      dimethylaminopyridine) and trans-[Cp*(dppe)Ru(MU-CN)Ru(dmap)4 (MU
      NC)Ru(dppe)Cp*][PF6 ]n (2[PF6 ]n , n=2, 3), which demonstrate cyanide/isocyanide
      isomerism, have been synthesized and fully characterized. 13+ [PF6 ]3 and 23+
      [PF6 ]3 are the one-electron oxidation products of 12+ [PF6 ]2 and 22+ [PF6 ]2 ,
      respectively. The results suggest that 1[PF6 ]3 is a class III mixed valence
      compound, whereas 2[PF6 ]3 might be an unusually symmetrical class II-III mixed
      valence compound composed of the two asymmetrical delocalized RuIII -NC-RuII
      mixed valence subunits.

PMID- 30182523
TI  - Predictors of nutrition care process and terminology use, applicability and
      importance within Asia-Pacific dietitians.
AB  - AIM: Many dietitians are yet to incorporate the Nutrition Care Process and
      Terminology (NCPT) into practice. The present study investigated factors
      predicting (i) NCPT use, (ii) perceived importance of NCPT implementation and
      (iii) perceived NCPT applicability to personal dietetic practice among dietitians
      in the Asia-Pacific region. METHODS: Dietetic association members from Australia,
      New Zealand and Singapore were invited to participate in an online survey
      assessing NCPT implementation, knowledge, and self-rated familiarity, attitudes,
      benefits, concerns, barriers, and enablers. Forward stepwise logistic regression
      used all factors to identify predictive dietetic characteristics for current NCPT
      use, importance or applicability to practice. RESULTS: A total of 377 dietitians
      (5%-55% of national dietetic memberships surveyed) completed at least one survey
      question. In logistic regression models, independent positive predictors of
      current NCPT users were knowledge (P = 0.003), confidence to implement (P =
      0.036), confidence to write nutrition diagnoses (P = 0.002) and experiencing
      managerial support (P = 0.004). Not seeing a reason to change was a significant
      negative predictor of NCPT use (P = 0.003). An independent positive predictor of
      dietitians viewing NCPT implementation as important was feeling that it will
      improve patient care (P < 0.001), while negative predictors were seeing minimal
      benefit in changing (P < 0.001) and a preference to continue with current routine
      (P = 0.015). Independent positive predictors of dietitians viewing NCPT as
      applicable to their practice were NCPT knowledge (P = 0.009), seeing the value of
      NCPT (P < 0.001) and attendance at workshops or conferences (P = 0.014).
      CONCLUSIONS: NCPT implementation may be enhanced thorough activities building
      confidence, gaining managerial corroboration and demonstration of NCPT benefits,
      including improved patient care.

PMID- 30182524
TI  - Designing Metallic MoO2 Nanostructures on Rigid Substrates for Electrochemical
      Water Activation.
AB  - In situ growth of metallic MoO2 films on fluorine-doped tin oxide (FTO) and MoO2
      powder in solution was achieved simultaneously by a simple hydrothermal process
      employing citric acid as the surfactant. The growth mechanism of MoO2
      nanostructures (NSs) at the heterogeneous interface and in homogeneous medium
      proceeds in a different manner in which seeds grow in a preferred orientation on
      FTO, whereas they propagate in all directions in solution. The high lattice
      matching of FTO and MoO2 favours the film growth which could not be obtained on
      other conventional substrates. The disc morphology of MoO2 nanostructures was
      changed to other diverse morphology by varying the synthesis conditions,
      particularly by the addition of nitric acid. A competitive effect of nitric acid
      and citric acid on the structure direction produced various shapes. The
      electrochemical water activation studies show that hydrogen-annealed MoO2 is an
      excellent hydrogen evolution reaction (HER) catalyst with good stability. H-MoO2
      film/FTO displays a low onset overpotential of72 mV with a Tafel slope of 84.1 mV
      dec-1 , whereas the powder form exhibits an onset overpotential of 46 mV with a
      Tafel slope of 71.6 mV dec-1 . The large active surface area, exposure of fringe
      facets of (110) and the lesser electrochemical charge-transfer resistance offered
      by the hydrogen-annealed MoO2 NSs play a major role in the enhanced HER activity.

PMID- 30182525
TI  - Iron and Cobalt Metallotropism in Remote-Substituted NHC Ligands: Metalation to
      Abnormal NHC Complexes or NHC Ring Opening.
AB  - Metallotropism of the M[N(SiMe3 )2 ]2 metal fragment in the tautomeric system IAR
      ?ACR involving imidazolium salts/N-heterocyclic carbenes with remote
      aminide/amine substituents, respectively, is manifested by its CNHC
      carbophilicity (R=tBu, M=Co, Fe) or NRaminido nitrogenophilicity (R=Cy, M=Co, Fe;
      R=Mes, M=Fe) and has been rationalized on the basis of steric and electronic
      effects. The thermolysis products of the [M{N(SiMe3 )2 }2 ]/ IAR ?ACR system are
      also substituent-dependent, leading to a rearranged aminide-functionalized aNHC
      Co2 complex of an unprecedented type or to ring-opened metallaketenimines; they
      are postulated to originate from different metalloisomers. The results are
      interpreted on the basis of the X-ray diffraction analysis of 11 new compounds.

PMID- 30182526
TI  - How Culture and Biology Interact to Shape Language and the Language Faculty.
AB  - Recent work suggests that linguistic structure develops through cultural
      evolution, as a consequence of the repeated cycle of learning and use by which
      languages persist. This work has important implications for our understanding of
      the evolution of the cognitive basis for language; in particular, human language
      and the cognitive capacities underpinning it are likely to have been shaped by co
      evolutionary processes, where the cultural evolution of linguistic systems is
      shaped by and in turn shapes the biological evolution of the capacities
      underpinning language learning. I review several models of this co-evolutionary
      process, which suggest that the precise relationship between evolved biases in
      individuals and the structure of linguistic systems depends on the extent to
      which cultural evolution masks or unmasks individual-level cognitive biases from
      selection. I finish by discussing how these co-evolutionary models might be
      extended to cases where the biases involved in learning are themselves shaped by
      experience, as is the case for language.

PMID- 30182527
TI  - Experiences of shame and guilt in anorexia and bulimia nervosa: A systematic
      review.
AB  - OBJECTIVES: Emotional states may play an important role in the development and
      maintenance of anorexia (AN) and bulimia nervosa (BN). This systematic review
      aimed to examine the evidence regarding the relationship that shame and guilt
      have with two eating disorders, AN and BN. METHODS: Four major databases (Pubmed,
      PsychINFO, Web of Science, Medline) were searched (up until April 2018) for
      studies measuring guilt or shame in clinically diagnosed AN and BN groups.
      Included papers were evaluated for risk of bias. RESULTS: Twenty-four papers met
      the inclusion criteria. Several methodological issues were noted within the
      reviewed studies, including a lack of longitudinal data and unaccounted
      confounding variables. Nonetheless, shame was typically more common in those with
      AN and BN than controls, was positively related to the severity of symptoms, and
      associated with the onset of eating disorder-related difficulties (e.g., binging
      or purging). Effect sizes were typically moderate to large. The role of guilt was
      less clear, with few studies and mixed results. DISCUSSION: There is preliminary
      evidence that shame is implicated in the aetiology of AN and BN presentations,
      whilst there is currently insufficient evidence of such a role for guilt. It
      remains unclear whether shame is a risk factor for the development of AN and BN
      or a consequence of these difficulties. PRACTITIONER POINTS: Elevated shame
      appears to be a feature of anorexia (AN) and bulimia nervosa (BN). Shame appears
      to fluctuate with the occurrence of eating disordered behaviours like binging,
      purging or restricted eating. Guilt is less consistently linked to AN and BN
      presentations. Interventions directed at shame may be helpful for these
      populations. A lack of longitudinal data means the temporal features of these
      relationships are still unclear.

PMID- 30182528
TI  - Depressive symptoms in Chinese assembly-line migrant workers: A case study in the
      shoe-making industry.
AB  - INTRODUCTION: Assembly-line migrant workers (AMWs), as a major workforce in
      China, may be at particularly high risk of depression due to their relative low
      social economic status and particular job characteristics. However, little is
      known about the frequency and characteristics of depression among Chinese AMWs.
      This study investigated the prevalence and correlates of depressive symptoms in
      Chinese AMWs. METHODS: In this cross-sectional survey, 915 Chinese AMWs from two
      shoe-making factories completed a standardized questionnaire to report their
      socio-demographics, physical health, migration, and work. They also reported
      their depressive symptoms by completing the Beck Depression Inventory-Short Form
      (BDI-SF). We conducted multiple logistic regression analysis to identify factors
      related to depression. RESULTS: We found that 31.7% of AMWs were clinically
      depressed (BDI-SF >= 8). The multiple regression model included age, self-rated
      physical health, pain, family relationships, having no good friends at the same
      factory, and working under high pressure. DISCUSSION: Our findings suggest that
      depression is common among Chinese AMWs. We argue that there is an urgent need
      for health care providers and factory managers to work on the early
      identification of AMWs, who are at high risk for depression. Psychological and
      psychiatric treatments are necessary in the Chinese labor-intensive industries.

PMID- 30182529
TI  - Renal Clearable Luminescent Gold Nanoparticles: From Bench to Clinics.
AB  - With more and more engineered nanoparticles being translated to the clinic, FDA
      has recently issued a draft guidance on nanomaterial-containing drug products
      with an emphasis on understanding their in vivo transport and nano-bio
      interactions in the physiological environment; so that nanoparticles can be
      designed in a way that they can target and treat diseases more efficiently than
      small molecules, have minimum accumulation in the normal tissues and organs and
      induce minimum toxicity and health hazards. In this review, we integrate this
      guidance with our ten-year studies on developing renal clearable luminescent gold
      nanoparticles. These gold nanoparticles highly resist serum protein adsorption,
      escape the liver uptake, target cancerous tissues through enhanced permeability
      and retention (EPR) effect, and report kidney dysfunction at early stages. In the
      meantime, "off-target" gold nanoparticles can be eliminated through the kidneys
      with minimum accumulation in the body. This revisit also allows us to identify
      future work towards the translation of renal clearable gold nanoparticles from
      bench to clinics.

PMID- 30182530
TI  - Evaluation of intravenous and subcutaneous administration of a novel, excipient
      free, nanoparticulate formulation of paclitaxel in dogs with spontaneously
      occurring neoplasia.
AB  - Carriers used to solubilize taxane chemotherapy drugs cause severe
      hypersensitivity. Nanoparticle formulations can provide improved dissolution and
      bioavailability of taxanes. Thus, a nanoparticulate, excipient-free formulation
      of paclitaxel (CTI52010) was evaluated in tumour-bearing dogs with intravenous
      and subcutaneous delivery. Tumour-bearing dogs were treated with intravenous
      CTI52010 using a modified rapid dose escalation scheme. Subcutaneous
      administration was then planned for a small cohort of dogs for comparison. For
      both groups, serial blood samples were collected after first dosing for
      pharmacokinetic analysis by LCMSMS. Tumour response was measured using RECIST
      criteria. Toxicity was recorded using VCOG-CTCAEv1.1. Fifteen dogs were treated
      with intravenous delivery at increasing dosages (80-136 mg/m2 ), with one
      objective response in the urethral component of a prostatic carcinoma (probable
      transitional cell carcinoma) and four dogs with durable stable disease (two
      carcinomas, two sarcomas). Pharmacokinetic data indicate a rapid initial clearing
      of the drug from serum followed by an extended elimination half-life, similar to
      normal dogs and suggesting reticuloendothelial clearance. Parameters and toxicity
      were highly variable and a maximally tolerated dosage could not be reliably
      confirmed. Three dogs were treated with subcutaneous delivery and no drug was
      detected in circulation, resulting in termination of the study. This novel
      formulation of paclitaxel is well tolerated in dogs and no unique toxicity or
      hypersensitivity was noted. The preliminary responses suggest biologic activity.
      The lack of systemic absorption after subcutaneous administration suggests a
      possible role for intratumoural anticancer therapy.

PMID- 30182531
TI  - The linker length of glucose-fipronil conjugates has a major effect on the rate
      of bioactivation by beta-glucosidase.
AB  - BACKGROUND: Endogenous plant beta-glucosidases can be utilized to hydrolyze pro
      pesticides and release the bioactive pesticide. Two related glucose-fipronil
      conjugates with different linkers structure, N-{3-cyano-1-[2,6-dichloro-4
      (trifluoromethyl) phenyl]-4-[(trifluoromethyl) sulfinyl]-1H-pyrazol-5-yl}-1-(2
      triazolethyl-beta-d-glucopyranoside)-1H-1,2,3-triazole-4-methanamine (GOTF) and N
      {3-cyano-1-[2,6-dichloro-4-(trifluoromethyl) phenyl]-4-[(trifluoromethyl)
      sulfinyl]-1H-pyrazol-5-yl}-2-aminoethyl-beta-d-glucopyranoside (GOF), were
      deglucolysated by beta-glucosidase both in vitro and in vivo at different rates.
      Here, the basis for these differences was investigated by revealing the kinetics
      of the reaction and by modeling molecular docking between enzyme and substrate.
      RESULTS: Results from kinetic study showed that the reaction rate was the main
      reason for the poorer rate of GOF hydrolysis with respect to GOTF. Modeling of
      substrate docking indicated that the spacer arm of glucose-fipronil conjugates
      affects the strength of non-covalent bonds within the active site and the
      position of fipronil within the pocket. Four glucose-fipronil conjugates and four
      corresponding aglycones were synthesized, and the hydrolysis data confirmed that
      the increased tether length between the bulky aglycone and glycone would lead to
      faster hydrolysis rate. The bioassay results indicated that most glucose-fipronil
      conjugates displayed moderate to excellent insecticidal activities in vivo
      against Plutella xylostella larvae. CONCLUSION: This study provides a potential
      strategy to optimize the substrate structure to enhance hydrolytic specificity in
      order to design appropriate phloem mobile pro-pesticides. (c) 2018 Society of
      Chemical Industry.

PMID- 30182532
TI  - Novel frameshift mutation in the insulin (INS) gene in a family with maturity
      onset diabetes of the young (MODY).

PMID- 30182533
TI  - Empowering Students to Innovate: Engagement in Organic Chemistry Teaching.
AB  - "... Students are creative and they love to solve tough problems. We need to
      support them as they learn, and give them opportunities to recognize their own
      potential. Allowing students to innovate is a winning formula ... Read more in
      the Guest Editorial by Neil K. Garg.

PMID- 30182534
TI  - Autologous platelet-rich gel treatment for diabetic chronic cutaneous ulcers: A
      meta-analysis of randomized controlled trials.
AB  - BACKGROUND: In recent years, many studies have reported that autologous platelet
      rich gel (APG) is an effective adjuvant treatment for chronic cutaneous ulcers in
      diabetics. The aim of this study was to explore the efficacy and safety of APG
      for the topical treatment of diabetic chronic cutaneous ulcers. METHODS: The
      China Biology Medicine (CBM), China National Knowledge Infrastructure (CNKI), VIP
      Database for Chinese Technical Periodicals (VIP), Chinese Wanfang database,
      PubMed, EMBASE, EBSCOhost, and Cochrane Library were systematically searched for
      relevant studies published up to 18 October 2017. Fixed- and random-effects
      models were used to calculate risk ratios (RR), odds ratios (ORs), and mean
      difference (MD) with 95% confidence intervals (95% CI). Subgroup analyses were
      conducted according to the Diabetic Foot Wagner Classification. RESULTS: Fifteen
      randomized control trials (RCTs) with 829 patients were eligible for inclusion in
      this analysis. Compared with standard care or conventional treatment, APG
      significantly improved the healing rate (RR 1.39; 95% CI 1.29, 1.50; P <
      0.00001), shortened the healing time (MD -9.18; 95% CI -11.32, -7.05; P <
      0.00001), and reduced the incidence of infection (OR 0.34; 95% CI 0.15, 0.77; P =
      0.009). CONCLUSIONS: Current evidence suggests that APG is effective and safe,
      and is feasible for use as an adjuvant treatment for diabetic ulcers, especially
      chronic refractory ulcers. However, more RCTs with a good design and of a high
      quality are needed before the use of APG can be implemented widely.

PMID- 30182535
TI  - 20th Asia Pacific League of Associations for Rheumatology Congress (APLAR), 6-9
      September 2018, Kaohsiung, Taiwan.

PMID- 30182537
TI  - [The science that has never been cited].
AB  - No Abstract available.

PMID- 30182536
TI  - Predictive variables of spontaneous micturition recovery after acute urinary
      retention in men with benign prostatic enlargement: An observational prospective
      study.
AB  - OBJECTIVE: Acute urinary retention (AUR) is the sudden and painful inability to
      urinate spontaneously. AUR is one of the most significant complications of benign
      prostatic enlargement. The management of AUR is based on transurethral
      catheterization. Subsequent therapy is uncertain, but AUR seems to benefit from
      the use of alpha-blockers. The aim of this study was to evaluate the variables
      that could predict which patients would recover spontaneous micturition after
      trial without catheter. METHODS: The present prospective observational study
      included men with AUR in an Italian tertiary care institute in 2016. Patients
      were catheterized and treated orally with fluoroquinolones, alpha-blockers, and
      Serenoa repens extracts. Preoperative variables as age, C-reactive protein (CRP),
      previous prostate-specific antigen values, urinary retention volume, prostate
      volume, and scores on a modified International Prostate Symptom Score
      questionnaire (IPSS-4), were investigated in relation to spontaneous micturition
      recovery. RESULTS: Mean (+/-SD) age was 68.4 +/- 7.1 years. Spontaneous and valid
      micturition recovery was observed in 11 patients (29.7%), whereas 26 (70.3%)
      needed to be catheterized again. The IPSS-4 score was significantly lower (9 vs
      17; P < .001) and CRP values were significantly higher (43.00 vs 1.00 mg/dL; P <
      .001) in patients who recovered spontaneous micturition. The IPSS-4 scores and
      CRP showed an area under the curve of 0.85 and 0.87, respectively. for the
      prediction of spontaneous and valid micturition recovery. CONCLUSION: CRP and
      IPSS-4 could be useful tools to predict spontaneous micturition recovery after
      catheterization associated with medical therapy for AUR.

PMID- 30182538
TI  - [Behavior of patients with patellofemoral osteoarthritis].
AB  - BACKGROUND: Patellofemoral osteoarthritis affects a great number of patients
      complaining chiefly of knee pain, treatment vary from conservative to surgical,
      especially arthroscopy. OBJECTIVE: The aim of this study was to show the behavior
      of a group of patients with patellofemoral osteoarthritis. MATERIAL AND METHODS:
      A descriptive and transversal study with a level of evidence IV and
      recommendation grade C in the provincial teaching hospital Manuel Ascunce
      Domenech in Camaguey city from January 2015 to April 2017 was performed in 96
      patients with the diagnosis of patellofemoral osteoarthritis, but 77 of them were
      selected as a non-probabilistic sample, based on selected criteria. RESULTS: Mean
      age was 52.2 years. Female sex, right patella and primary etiology prevailed.
      Rest pain was the most common symptom. There is a strong correlation between
      Iwano T and Outerbridge RE classifications systems. In general, more than one
      compartment of the knee is aff ected in patellofemoral osteoarthritis, isolated
      presentation is rare and treatment by arthroscopy is of great help. CONCLUSIONS:
      Patellofemoral osteoarthritis is a common disease, patients usually complain of a
      great number of symptoms and signs. Patellofemoral osteoarthritis is usually
      associated to aff ection of other compartments and patients may be treated by
      arthroscopy.

PMID- 30182539
TI  - Treatment algorithm for Charcot foot and surgical technique with circular
      external fixation.
AB  - BACKGROUND: Charcot neuroarthropathy (CNA), commonly known as Charcot foot, is
      one of the most debilitating complications of diabetes mellitus. Patients with
      plantar ulcer and osteomyelitis (OM) due to Charcot foot represent a high cost
      for health systems and society in general. The amputation risk for ulcerated
      Charcot patients is 12 times higher than general population under 65 years old.
      MATERIAL AND METHODS: In this article we present the CNA treatment protocol we
      use in our center. We also make a detailed description of the surgical technique
      "single stage surgery" with circular external fixation. RESULTS: Our CNA
      treatment protocol covers the most common presentations of this severe
      neuropathic complication. With the "single stage surgery" using circular external
      fi xation we achieve an ulcer-free foot, successful treatment of the OM,
      correction of the deformity, diminished the cost of treatment, avoided amputation
      and prevented recurrence of the ulcer. CONCLUSIONS: The use of a treatment
      algorithm based on the current literature, can be an invaluable tool in the
      treatment of these complex patients. The circular external fixation has proven to
      be the only reliable tool for treating complex Charcot foot in the context of
      poor bone stock, active ulcers, soft tissues problems and OM.

PMID- 30182540
TI  - [Shoulder injuries in the elderly and their functional impact on the DASH scale].
AB  - INTRODUCTION: Disabling shoulder problems in the elderly are common. OBJECTIVE:
      To quantify the diagnoses found in 100 consecutive shoulders cases in
      rehabilitation and its functional impact on the DASH scale. MATERIAL AND METHODS:
      100 consecutive patients with age 65 years received in the Rehabilitation
      Department, performing diagnosis and functional assessment in the DASH scale.
      RESULTS: Distribution by gender with predominance of the female (67%); the age
      showed variation from 65 to 98 years with average and SD 78 +/- 12. Ten different
      diagnoses were found: supraspinatus tendon rupture (58%); gleno-humeral
      osteoarthritis (11%); impingement syndrome (9%); proximal humeral fracture (9%);
      acromio-clavicular osteoarthritis (7%); long biceps tendon rupture (2%); scapula
      fracture (1%); humeral head avascular necrosis (1%); neglected gleno-humeral
      dislocation (1%) and circumflex nerve injury (1%). The distribution corresponded
      to 52% right, 40% left and 8% bilateral. The DASH scale showed variation from 94
      to 52% with mean and SD 71 +/- 22.3. Elderly shoulder problems are associated
      with disability, its relation with DASH is not clear.

PMID- 30182541
TI  - [Comparison of the functional outcomes of patients with arthroscopic repair of
      massive rotator cuff ruptures alone or combined with acromioplasty or biceps
      tenotomy].
AB  - BACKGROUND: The rotator cuff injury it is one of the most common causes of pain
      and functional disability of the shoulder with an annual reported incidence of
      4.5 million cases in the United States. It is one of the leading causes of pain
      of shoulder in patients older than 60 years. In Mexico, there are no reports of
      the incidence or the results of arthroscopic repair of massive rotator cuff
      lesions alone or combined with other procedures. OBJECTIVE: To evaluate the
      clinical evolution of patients post-surgery of arthroscopic rotator cuff massive
      injury repair AR-RCMI alone or in combination with other techniques. METHODS:
      Evaluation of records of patients with AR-RCMI post-surgery, comparing the
      results of the scales: simple shoulder test and VAS before and after surgery with
      a follow up of 2.6 years. The combined procedures were acromioplasty, tenotomy of
      biceps or both. RESULTS: 65 patients with diagnosis of massive injury; with an
      average age of 62.8 years (SD +/- 9. 42), 27.7% were men and 72.3% women. The
      evaluation was conducted in four groups: arthroscopic repair (AR); arthroscopic
      repair + biceps tenotomy (AR + BT); arthroscopic repair + acromioplasty (AR + A)
      and arthroscopic repair + biceps tenotomy + acromioplasty (AR + BTA). All groups
      showed significant reduction in pain: AR (-44.1%, p = 0.0001), AR + A (-36.9%, p
      = 0.001), AR + BT (-36.3%, p = 0.0001), AR + BT + A (-38.5%, p = 0.0001). All
      groups had significant improvement in function with the SST scale.

PMID- 30182542
TI  - [Strength and function of hand before and after release of carpal tunnel in
      patients with type 2 diabetes mellitus by open and endoscopic approach. Case
      control study].
AB  - BACKGROUND: Carpal tunnel syndrome (CTS) is the upper extremity neuropathy more
      frequent. Treatments led to the entrapment of the median nerve in the carpal
      tunnel are more complicated and the results less promising and unsatisfactory in
      diabetic patients. The objective of this study is to compare the results of
      strength and hand function in healthy patients against patients with diabetes
      mellitus type 2 (DM2) with a diagnosis of CTS before and after the open and
      endoscopic release of the carpal tunnel. MATERIAL AND METHODS: This is an
      observational, retrospective and descriptive study for a period of five years
      where we evaluated the results in healthy patients and with DM2, with diagnosis
      of CTS who underwent surgical treatment by open or endoscopic approach; we
      applied the DASH questionnaire, force grip and clamp fine measurements, presence
      of infection, pain and complications. RESULTS: The results of 86 patients
      evaluated, showed a statistical association in the decrease in scores on the
      functional scale DASH with both approaches, association between remission of
      hypoesthesias in healthy patients with either of the two approaches as opposed to
      diabetic patients and association between developing DM2 and complications in the
      short term. CONCLUSION: Both approaches improve symptoms and function of the hand
      in healthy and diabetic patients, but the fi rst group will present cases of
      complete remission in contrast to the group of diabetic patients.

PMID- 30182543
TI  - [Rehabilitation of hip fractures. Systematic review].
AB  - INTRODUCTION: Hip fractures are considered among one of the most disabling
      injuries in patients older than 60 years of age. This fractures are associated
      with a high incidence of mortality and it is the leading cause of hospital
      admission that requires surgical treatment in Orthopaedic Trauma Centers.
      METHODS: This systematic review aimed to group, classify and report the best
      level of evidence of physical therapy and rehabilitation of patients that have
      been treated with osteostynthesis after trochanteric or subtrochanteric fracture.
      The outcomes of efficacy and safety were return to activities of daily living,
      independence and rate of complications. RESULTS: We identified 3,889 abstracts
      from PubMed, and 1,567 abstracts from other sources, after eliminating
      duplicates, and posterior to a thorough screening 378 abstracts were read. From
      these, 316 abstracts were excluded, and 62 articles were considered eligible.
      After reading for relevant outcomes 41 articles were excluded. Synthesis was
      based in 21 studies. CONCLUSIONS: Long term results of specialized physical
      therapy, appear to be crucial in the first months after surgery, and not that
      important after the four months after surgery. Recent literature supports that
      the differences of daily activities and independence of the patients that survive
      a hip fracture tend to be similar with no difference in the type of physical
      therapy.

PMID- 30182544
TI  - [Shoulder arthroplasty complications: case report].
AB  - BACKGROUND: Infection and instability are the complications of prosthetic
      shoulder surgery of more difficult management. Instability builds up to half of
      the cases, while the fungal infection accounts for less than 1% of all and can
      cause severe damage to bone and soft tissue. METHODS: In this case clinical
      fungal infection by Candida parapsilosis is presented in a shoulder
      hemiarthroplasty indicated by a fracture of the proximal humerus. He received
      surgical treatment in two-stages and administration of fluconazole for eight
      weeks prior to the second surgical time. In revision surgery was placed a reverse
      prosthesis as definitive treatment; however, the patient suffered several
      episodes of dislocation in the postoperative period; a second revision prosthetic
      surgery was necessary to use more stable components. During this surgery, we
      extracted samples that were analyzed, obtaining negative results for infection.
      RESULTS: Now after three years of follow-up, the patient is well, no limitations
      in their daily work and has a Constant Score of 50.5. DISCUSSION: We report our
      experience in this exceptional situation. We know, this is one of the first cases
      where the fungal infection and dislocation prosthetics in the same patient meet.
      This situation is a challenge for the surgeon, which has to treat complications
      two practically at the same time; we do not have scientific evidence to establish
      a criterion unified for the treatment of complications after surgery for revision
      of arthroplasty of the shoulder, especially in reverse or mega-denture
      prosthesis.

PMID- 30182545
TI  - [Management of the chronic compartment syndrome of the leg in athletes.<br>
      Presentation of 2 cases and review of literature].
AB  - A problem commonly undiagnosed, severe and diffi cult to treat is chronic
      compartment syndrome in athletes. This pathology in its acute phase requires a
      diagnosis and treatment early to avoid muscle necrosis and neurological injury.
      Also, in chronic cases, the diagnosis is mainly clinical and the complete
      liberation of all compartments of the leg is essential. I review the literature
      of management of this pathology and two cases with specific treatment are
      presented. The objective is to provide evidence-based guidance for both chronic
      and acute treatment of chronic compartment syndrome in athletes to reduce the
      delay in the diagnosis and implement effective therapeutic measures for the
      improvement of the athletes and to avoid as much as possible the presentation of
      complications and sequelae in this group of patients.

PMID- 30182546
TI  - [Acetabular revision at 96 years old. Is the age a limiting factor in revision
      surgery for hip replacement?]
AB  - This is a case report of a 96 year old woman with pain and functional impotence
      in her left hip after fall. X rays were performed and loosening of the acetabular
      component was appreciated. After discussion of treatment options, it was decided
      to cement an acetabular component for a double mobility head. There was a high
      rate of medical and surgical complications in revision of hip arthroplasty in
      elderly patients. However, it can also offer important benefits in terms of
      independence and quality of life and even increase life expectancy in patients
      with less comorbidity. In our case after six months of follow-up the patient was
      able to walk alone using a walker. In the literature review, age does not appear
      as a limit for the surgical indication. Preoperative medical optimization of the
      patient as well as shorter operative time and blood loss, are important factors
      for good results of these cases.

PMID- 30182548
TI  - [72 years of existence].
AB  - No Abstract available.

PMID- 30182547
TI  - [Review of femoral component with proximal metaphyseal reconstruction using
      allograft cortical struts in a multioperated patient. Case report].
AB  - INTRODUCTION: Periprosthetic hip fractures are those that occur at the femoral
      and acetabular level. These fractures are associated with a wide variety of
      problems such as comminution, loose of bone stock and loosening of the femoral
      stem. Treatment of these fractures has historically been associated with high
      rates of treatment failures, complications and unsatisfactory outcomes.
      OBJECTIVE: To present the clinical-radiographic case of the treatment of a
      periprosthetic hip fracture, with a femoral revision and metaphyseal
      reconstruction with cortical strut allograft and cerclage cables, in a
      multioperated patient. MATERIAL AND METHODS: We present the case of a patient
      with a dislocation of a revision total hip prosthesis with a periprosthetic
      fracture type B3 of the Vancouver classification, who underwent a revision of the
      femoral component and a proximal metaphyseal reconstruction of the femur with
      cortical strut allograft and cerclage cables. RESULTS: The patient had an
      adequate evolution at the postoperative year, walking with a cane, radiographic
      control with adequate congruence of the prosthetic components and data of
      consolidation of the fracture. DISCUSSION: In the treatment of periprosthetic
      fractures, reconstruction can be done with use of cortical strut allograft and
      cerclage cables, with good functional and radiological results.

PMID- 30182549
TI  - Epidemiological and radiological profile of patients with degenerative scoliosis:
      20 year experience at a referral institute.
AB  - BACKGROUND: Adult degenerative scoliosis is a complex three-dimensional
      rotational deformity, in a previously straight spine, resulting in sagittal and
      axial disbalance. MATERIAL AND METHODS: This retrospective study presents the
      casuistry of patients 40 to 80 years old with adult degenerative scoliosis who
      underwent surgery in a referral institute from January 1994 to December 2013.
      RESULTS: The prevalence was 0.087% (CI 95% 67.8-111), with a median age of 64.9
      +/- 9.4 years old, increased frequency in women and older adults. The prevalence
      of spondylolisthesis associated with degenerative scoliosis was 21%. The
      estimated risk for scoliosis in women was OR = 2.37 (CI 95% 1.35-4.15), while men
      showed OR = 0.4 (CI95% 0.24-0.73). The risk for spondylolisthesis associated to
      degenerative scoliosis was in men OR = 1.87. CONCLUSIONS: The prevalence in our
      experience is low and the sample age was higher; while gender, severity of the
      curve and presence of spondylolisthesis and olistesis were similar to the
      reviewed literature.

PMID- 30182550
TI  - [Frequency of complications in patients older than 60 years with hip fracture].
AB  - INTRODUCTION: According to figures from INEGI 2009, indicate that one in 12
      Mexican women and one in 20 men over 65 will suffer a hip fracture. Is expected
      to reach 110,055 patients in the year 2050. Femoral neck stress fractures are
      more common in women and consist of 5 to 10%. There is a high number of patients
      with hip fracture complications, secondary to multiple factors which have been
      little studied and this limits its prevention. MATERIAL AND METHODS: A
      retrospective, observational and transversal study in senior citizens between
      January and December 2016 with hip fracture was conducted. Through collection of
      demographic data: age, sex, address, as well as type of fracture, type of
      management, primary diagnosis: ICD 10 S72 fracture of hip, hospital stay, surgery
      carried out and place of destination subsequent to discharge from the unit.
      RESULTS: The most affected gender was female. Within the main complications it
      correlates with delirium considering the average hospital stay of one day thrown
      outcomes, says that hospital stays are relatively short compared to other types
      of fractures. As in the international literature, the Transtrochanteric fracture
      is the main type of fracture; However in terms of surgical management of higher
      prevalence was hemiarthroplasty type Thompson followed by closed reduction
      internal fixation with DHS system placement.

PMID- 30182551
TI  - [Subacromial sodium hyaluronate injection for the treatment of chronic shoulder
      pain: A prospective series of eighty patients].
AB  - OBJECTIVE: Our purpose was to assess the effectiveness of hyaluronic acid
      infiltrations for chronic shoulder pain as an alternative to the non-surgical and
      surgical treatments that are currently available. MATERIAL AND METHODS: This is a
      prospective study of 80 consecutive patients suffering from chronic shoulder pain
      followed for twelve months. Five subacromial hyaluronic acid injections on five
      consecutive weeks were administrated to all patients. RESULTS: A significant
      improvement within the whole group after six months was observed. Constant score
      improved by 7.7 points, DASH questionnaire decreased by 5 points and Visual
      Analog Scale for pain decreased by 1.6 points. Patients with history of less than
      24 months of pain responded better to treatment. Females responded better.
      Patients with decreased subacromial space or cuff tear in the MRI improved but
      patients diagnosed by the MRI of acromioclavicular osteoarthritis worsened in all
      scales assessed. DISCUSSION: Subacromial hyaluronic acid injections are specially
      effective in patients with history of less than 24 months of pain, a decreased
      subacromial space or partial or total cuff tear but, in our experience, its
      result is not good in patients with acromioclavicular osteoarthritis.

PMID- 30182552
TI  - [Prevalence of complications related to the removal of the syndesmotic screw].
AB  - BACKGROUND: Removal of the syndesmotic screw is a currently-disputed procedure.
      Most of the publications that promote avoid this procedure considered that the
      rate of complications is high. The aim of this work was to determine the rate of
      complications related to the removal of the syndesmotic screw to learn about the
      safety and compare the results with the international literature. MATERIAL AND
      METHODS: A descriptive, observational, retrospective and cross-sectional study in
      which took a sample of all cases operated of removal of the syndesmotic screw at
      our hospital from February 2015 January 2016 for the prevalence of the
      complications associated with this procedure. The statistical analysis was
      descriptive. RESULTS: A total of 207 patients were studied. Five patients with
      complications were observed (2.41%). Two cases with wound dehiscence, two cases
      with superficial infection (1.92%), and a case with subsequent diastasis of the
      syndesmosis, with pain associated to instability (0.48%) which required revision
      surgery. CONCLUSIONS: In the sample of our hospital, the prevalence of
      complications related to the syndesmotic screw removal was less than that
      reported in the literature so far; Thus we could say that is a safe procedure,
      with low risk for infection and post-traumatic instability of the ankle.

PMID- 30182553
TI  - [Biomechanical analysis through numerical simulation of rupture of the tibial
      posterior tendon in valgus flat foot: a cadeveric study].
AB  - The insufficiency of the posterior tibial tendon is the most common acquired
      cause of pain related to valgus flatfoot deformity in adults. The acquired
      flatfoot adult is a very painful symptomatic deformity resulting from a gradual
      stretching (attenuation) of the posterior tibial tendon and ligaments that
      support the arch of the foot. The progressive pain acquired flatfoot adult
      affects four times more women than men. Some factors that contribute to increased
      risk of acquired flatfoot in adults, are diabetes, hypertension and obesity. It
      is thought that the combination of the following events is the cause of acquired
      flatfoot adult. Johnson Strom classification modified by Mayerson evaluates in 4
      stages. This study was divided into 3 stages: Stage 1: Dissection and three
      dimensional analysis of the tendon, Step 2: Application of tools bioengineering
      to determine the causes of rupture of the tibial tendon: Stage 3: Evaluation of
      24 patients with flatfoot disease valgus for describe the deformity.

PMID- 30182554
TI  - [Use of metaphyseal stems "Proxima" DePuy: our experience to more than five
      years].
AB  - The total hip arthroplasty with short stems to preserve bone is a good choice in
      young patients that expected future revision surgery, it is also a good choice
      when we use approaches for minimal invasive surgeries. In this study, we have
      evaluated, clinically and radiologically, our experience in total hip
      arthroplasty with the use of short stems and metaphyseal anchorage. In total we
      have involved 23 patients with a mean age of 50.2 years (range 45 to 69 y/o) at
      the time of surgery. The median follow-up was greater than five years. There was
      a slight Varus femoral stem in three cases, one of them in severe varus. The
      latter presented continuous pain in the lateral aspect of the thigh that
      increased with time, with a diaphyseal reaction and an increase in radiolucencies
      around the stem that required revision surgery 12 months postoperative. A longer
      follow-up is required to analyze the results and confirm the durability of the
      observed clinical findings. Patients were evaluated radiological and clinically
      using the scale of Merle dAubigne (MD).

PMID- 30182555
TI  - [Clinical and functional results of the Brostrom-Gould technique for lateral
      ankle instability: evaluation with three scales].
AB  - BACKGROUND: The most frequent sequel to the ankle sprain is the instability of
      the lateral ligament complex; the results of surgical treatment have not been
      evaluated with multiple scales simultaneously. The objective of the study was to
      assess the clinical and functional results with three scales in patients with
      lateral instability of ankle undergoing Brostrom-Gould technique, using for
      fixation, anchors with suture to distal fibula. MATERIAL AND METHODS: The design
      of the study was cross-sectional and descriptive; we included patients with
      lateral instability of ankle and partial or complete rupture of the APA or CP
      ligament subject to repair with Brostrom-Gould technique. Magnetic resonance
      imaging was performed to confirm the diagnosis; clinical and functional outcomes
      were determined with three scales: EVA, SF-36 and AOFAS. Patients were evaluated
      at six months, or more, after the surgical procedure. RESULTS: We included 13
      patients; quality of life (SF-36 questionnaire) showed a good result with average
      score of 90; 10 (77%) patients showed excellent results in function, absence of
      pain and alignment of the ankle (AOFAS 90-100). Also found significant
      improvement in pain (presurgical EVA: 6, compared with 1 in the postoperative
      period). CONCLUSIONS: The surgical procedure showed excellent results, in the
      short term with resolution of pain and ankle stability.

PMID- 30182556
TI  - [Usefulness of the arthrogram in the decision therapy in children with
      developmental dysplasia of the hip from 3 months to 3 years of age].
AB  - OBJECTIVE: To evaluate the utility of arthrography as a tool in therapeutic
      decision in developmental dysplasia of hip (DDH). MATERIAL AND METHODS: 19
      children with true DDH with age between three months and three years, without
      previous surgical treatment, with Tonis II or III, and complete X-rays. For each
      case; therapeutic decision was registered for X-rays and arthrography by three
      independent observers, we took like standard, surgery in each patient necessary
      to obtain a concentric reduction and good acetabular coverage. RESULTS: 20 cases,
      19 patients. 18 unilateral, 1 bilateral. They were 17 girls (89%) and 2 children
      (11%). Average Age: 1 year 3 months (4 months to 2 years 11 months). 11 Tonis II
      (55%) and 9 Tonis III (45%). The intraclass coefficient of correlation (ICC) in
      relation to the decision therapeutic radiographic was of 0.8933 and for the
      arthrography of 0.7205. And ICC of the decision therapeutic radiographic in
      connection with the standard was of 0.7933 and for the arthrography it was of
      0.6219. We confirm that in our 20 cases, the utility of the arthrography (ICC
      0.6219), is smaller to the X-rays (ICC 0.7933). The utility of the arthrography
      was bigger in the patients with Tonis II, and an age between nine months and two
      years.

PMID- 30182557
TI  - [Congenital Analgesia: report of 2 cases].
AB  - Congenital analgesia is a rare condition, reporting in the international
      literature in rare cases since 1932, when it was first described. Its cause has
      been the subject of development of multiple theories and studies through the
      years. Currently various studies and experiments as its origin point mutation in
      the gene encoding SC9NA sodium channels, which have an important role in
      nociceptive transmission signals in the human body. The purpose of this study is
      to present two cases that were valued in the department of pediatric orthopedics
      at UMAE HTYOLV, patients whose insensitivity to pain has produced significant
      injuries that were once cause for valuation of the hospital.

PMID- 30182558
TI  - [Clinical and molecular study in a family with multiple osteochondromatosis].
AB  - We present two cases of a family with the diagnosis of multiple
      osteochondromatosis, which was confirmed by molecular study with nonsense in
      heterozygosis mutation c.1219CT, (p.Gln407Stop) in the EXT1 gene. In these cases,
      the Madelung deformity was presented in one patient as an uncommon finding and
      chondrosarcoma as a feared complication in the other case, highlighting
      intrafamilial variation, which is why individual and interdisciplinary evaluation
      is recommended. In addition, before a genetic entity should provide adequate and
      timely family genetic counseling to all its members.

PMID- 30182559
TI  - [Application of minimally invasive cosmetic dentistry in the clinics of pediatric
      dentistry].
AB  - With the minimally invasive treatment attracting considerable attention in the
      field of dentistry, a series of oral minimally invasive treatment technologies,
      including minimally invasive cosmetic dentistry (MICD) technology, is emerging.
      Children, as a special group of patients, are in the critical stage of the
      initial formation of psychological structure. Therefore, children's dental
      treatment should not be limited to restoring function and relieving pain. The
      development, aesthetics, and physical and mental health should also be given
      attention. Therefore, in recent years, MICD technology has been widely used in
      diagnosis and treatment of pediatric dentistry. This review provides a detailed
      introduction regarding a series of techniques in pediatric dentistry.

PMID- 30182560
TI  - [Periodontal status assessment before orthodontic treatment and opportune moment
      selection for orthodontic treatment].
AB  - The aesthetic demands of teeth by the public have improved with the increase in
      the living standard. Orthodontics, which is a method of aesthetic dentistry, is
      becoming increasingly important. Orthodontic treatment mainly involves the
      application of orthodontic force to the teeth and guides the reconstruction of
      the periodontal tissue, thereby changing the position of the teeth at the
      occlusal bone. Orthodontic treatment can also improve the dental occlusion caused
      by dentition crowding and teeth mobility to achieve long-term stability of
      periodontal tissue. The number of patients with periodontal disease is high in
      China, and the number of patients with periodontal disease that are eager to
      receive orthodontic treatment is increasing. Hence, the periodontal status during
      the orthodontic therapy should be explored along with periodontal therapy and
      orthodontic treatment. This article briefly demonstrates the assessment criteria
      of periodontal status before orthodontic treatment, the opportune moment
      selection for orthodontic treatment, and the supportive periodontal therapy. This
      study helps dentists develop individualized treatment programs and win a
      balanced, stable, and aesthetic impression.

PMID- 30182561
TI  - [Link between sortase A function and cariogenicity of Streptococcus mutans: a
      preliminary metabolomics analysis].
AB  - OBJECTIVE: This study intends to explore the mechanism underlying the support of
      sortase A (SrtA) of the cariogenicity of Streptococcus mutans (S. mutans).
      METHODS: We performed a metabonomics study based on 1H nuclear magnetic resonance
      spectroscopy (NMR), in which we compared the extracellular metabolites of wild
      type S. mutans UA159 with those of its SrtA-deficient strain. Metabolite
      differences among strains were identified using a combination of principal
      component analysis and orthogonality partial least square discriminant analysis.
      RESULTS: Several differences corresponding mostly to unknown metabolites were
      identified. Some amino acids such as leucine and valine (delta 0.92*10-6-1.20*10
      6), lactic acid ( delta1.28*10-6), oxoglutaric acid (delta 3.00*10-6), and
      glycine (delta 3.60*10-6) differed among strains. CONCLUSIONS: This work
      establishes the feasibility of using 1H NMR-based metabonomics to provide leads
      for research into molecular factors that promote caries. The database of
      microbial metabolites should be also improved in further studies.

PMID- 30182562
TI  - [Human osteoprotegerin inhibits osteoclasts and promotes hydroxyapatite to repair
      the mandibular defects in ovariectomized rats].
AB  - OBJECTIVE: This study aims to investigate the effect of human osteoprotegerin
      (hOPG) gene-modified rat bone marrow mesenchymal stem cells (rBMSCs) combined
      with hydroxyapatite (HA) scaffolds on the repair of mandibular defects in
      ovariectomized rats. METHODS: rBMSCs were transfected with adenovirus carrying
      pDC316-hOPG-EGFP. The expression of hOPG and the inhibition of osteoclast
      function were detected by Western blot and bone-grinding experiment respectively.
      The model of mandibular bone defect in rats with osteoporosis was established;
      HA, untransfected rBMSCs-conjugated HA, and transfected rBMSCs-conjugated HA
      scaffolds were implanted into the mandibular bone defects. After six weeks,
      tartrateresistant acid phosphatase staining and hematoxylin-eosin staining were
      used to observe the number of osteoclasts and repair of bone defect. RESULTS:
      Adenovirus carrying hOPG gene in vitro were successfully transfected into rBMSCs.
      The hOPG with anti-osteoclast activity was expressed by hOPG-rBMSCs, and rBMSCs
      expressing hOPG combined with HA scaffolds promoted mandibular defect repair.
      CONCLUSIONS: rBMSCs transfected with hOPG gene inhibited the function of
      osteoclasts both in vitro and in vivo, and transfected rBMSCs combined with HA
      scaffolds promoted the repair of mandibular defects in rats with osteoporosis.

PMID- 30182563
TI  - [Comparative study of processed autogenous tooth bone and xenogeneic bovine bone
      in repairing an alveolar bone defect].
AB  - OBJECTIVE: This study was conducted to counter the osteogenesis effects of
      processed autogenous tooth bone and xenogeneic bovine bone following tooth
      extraction and to provide an experimental basis for clinical applications.
      METHODS: Central incisors were extracted with general anesthesia on both sides of
      a maxillary arch in 12 rabbits, which were randomly divided into three groups,
      thereby containing four rabbits in each group. Three rabbits were assigned to the
      experimental groups and one was for the control group. In the experimental
      groups, the xenogeneic bovine bone was applied to the left incisor socket,
      whereas the processed autogenous tooth bone was applied to the right incisor
      socket. The blank control group only extracted the teeth and did not implant any
      bone powder. The three groups died after 4, 8, and 12 weeks, respectively. A
      mineralization degree of new bone tissues was observed by fluorescence staining
      and the formation of a new bone was observed by histology. RESULTS: The
      sedimentary mineralization rate was greater in the processed autogenous tooth
      bone than in the xenogeneic bovine bone (P<0.05). The trabecular bone of the
      xenogeneic bovine bone was sparse and slender. The left sockets, which were
      filled with the xenogeneic bovine bone, had more woven and less lamellar bones
      than the right sockets, which were filled with the processed autogenous tooth
      bone. CONCLUSIONS: The processed autogenous tooth bone offers more advantages as
      a bone-grafting material than the xenogeneic bovine bone in terms of bone
      increment.

PMID- 30182564
TI  - [Role of neuropeptide substance P and the bone morphogenetic protein signaling
      pathway in osteogenic differentiation of ST2 cells].
AB  - OBJECTIVE: This study aimed to investigate the role and mechanism of neuropeptide
      substance P (SP) in ST2 cell (bone mesenchymal stem cells of mice) osteogenic
      differentiation to provide a basis for the treatment of temporomandibular joint
      osteoarthritis. METHODS: Third-generation ST2 cells were cultured with different
      concentrations of SP (0, 10-10, 10-8, 10-6, and 10-5 mol.L-1). After 24, 48, and
      72 h, cell proliferation was detected by CCK-8. The ST2 cells were cultured with
      10-6 mol.L-1 SP for 1, 3, 5, and 7 days. Subsequently, the expression of alkaline
      phosphatase (ALP), collagen typeI(CollaI), and osteocalcin (OCN) in the culture
      supernatant was tested by enzyme-linked immunosorbent assay (ELISA). ALP activity
      was detected by immunofluorescence staining. The ST2 cells were cultured with SP,
      Noggin (inhibitor of the bone morphogenetic protein signaling pathway),
      SP+Noggin, and 2% fetal bovine serum, respectively. Finally, the expression of
      ALP, CollaI, and OCN in the culture supernatant was tested by ELISA. RESULTS: CCK
      8 showed that the effect of cell proliferation was most obvious when the SP
      concentration was 10-6 mol.L-1 (P<0.01). The ELISA results demonstrated that ALP
      expression significantly increased at day 5 compared with that in the control
      group (P<0.01), whereas the expression of CollaIand OCN significantly increased
      at day 7 (P<0.05). Immunofluorescence results showed that ALP activity was
      strongest at day 5. The expression of ALP, CollaI, and OCN decreased after Noggin
      addition (P<0.05). CONCLUSIONS: SP can promote the proliferation and osteogenic
      differentiation of ST2 cells, and the bone morphogenetic protein signaling
      pathway may be involved in this process.

PMID- 30182565
TI  - [Correlations between the T helper cell 17/regulatory T cells balance in
      peripheral blood of patients with oral lichen planus and clinical
      characteristics].
AB  - OBJECTIVE: This study aimed to investigate the ratio of T helper cell 17 (Th17)
      and regulatory T cells (Treg) in peripheral blood of oral lichen planus (OLP) and
      explore the pathogenesis of its possible role and significance. METHODS: The
      peripheral blood samples were obtained from 33 patients with OLP (15 cases of
      reticular OLP and 18 cases of erosive OLP) and 17 healthy controls. The
      percentages of Th17 and Treg cells were detected by flow cytometry (FCM). Real
      time fluorescence quantitative polymerase chain reaction (qPCR) technique was
      used to detect the expression levels of retinoid-related orphan nuclear receptor
      gammat (RORgammat) and forkhead box 3 (Foxp3). RESULTS: The proportions of Th17,
      Treg cells, and their transcription factors (RORgammat and Foxp3) in OLP were
      higher than those in the control groups (P<0.05). By contrast, in Treg cells and
      Foxp3, no significance was observed between erosive OLP and reticular OLP.
      Th17/Treg ratio increased in OLP. This ratio was significantly increased in
      erosive OLP compared with those in the control groups and reticular OLP (P<0.01).
      Nevertheless, no significance was noted between reticular OLP and control groups.
      Statistical analysis demonstrated positive correlations among Th17 cells,
      Th17/Treg, and clinical characteristics (r=0.66, P=0.00; r=0.66, P=0.00; r=0.52,
      P=0.00; r=0.50, P=0.00). Positive correlations also existed between Th17 and Treg
      cells (r=0.39, P=0.03). CONCLUSIONS: Th17 cells, Treg cells, and their ratios all
      increased in the peripheral blood of OLP. Moreover, the imbalance inTh17/Treg may
      play a role in the pathogenesis of erosive OLP.

PMID- 30182566
TI  - [Relationship among gingival thickness, underlying alveolar bone thickness, and
      sagittal root position in the maxillary anterior].
AB  - OBJECTIVE: This study aimed to explore the relationship among gingival thickness
      (GT), underlying alveolar bone thickness (BT), and sagittal root position in the
      maxillary anterior measured by cone-beam computed tomography (CBCT). The
      theoretical foundation was applied to aesthetic dentistry, implant treatment
      planning, and therapeutic effect assessment. METHODS: A total of 40 young
      volunteers with healthy periodontal status were involved in this research [16
      males and 24 females aged 23-34 years with a mean age of (26.30+/-2.29) years].
      Three records were measured by CBCT. GT was measured at the cemento-enamel
      junction level. Buccal BT was measured at three locations: 1, 3, and 5 mm below
      the alveolar crest, along the sagittal angle between the long axis of teeth, and
      along the long axis of the respective alveolar bone. RESULTS: The average GT and
      alveolar BT thicknesses were (1.08+/-0.34) mm and (0.79+/-0.29) mm, respectively.
      The average angle between teeth and alveolar bone was 18.01 degrees +/-8.96
      degrees . BT was positively associated with GT (r=0.293, P=0.001). The BT of
      canine was positively associated with the angle between teeth and alveolar bone
      (r=0.457, P=0.003). CONCLUSIONS: BT was relatively thin. An angle was found
      between the long axis of teeth and that of the alveolar bone. BT was positively
      associated with GT. An accurate diagnosis of GT, underlying alveolar BT, and
      sagittal root position in the maxillary anterior is necessary before implant
      surgery to devise an appropriate implant treatment plan and achieve a predictable
      esthetic outcome.

PMID- 30182567
TI  - [Correlation between parental rearing patterns and self-consciousness of
      adolescents with cleft lip and palate].
AB  - OBJECTIVE: This study aimed to investigate the current situation of parental
      rearing patterns and self-consciousness of adolescents with cleft lip and palate.
      The relationship between parental rearing patterns and self-consciousness of
      adolescents was also analyzed to provide evidence for psychological intervention.
      METHODS: The study was carried out on 400 adolescents (11-25 years old) with
      cleft lip and palate. The subjects were assessed with self-consciousness scale
      for patients with cleft lip and palate and Egna Minnen av Barndoms Uppforstran
      family rearing questionnaires to evaluate the current status of self
      consciousness and parental rearing patterns in adolescents with cleft lip and
      palate and the relevance of the two factors. RESULTS: A total of 380 valid
      questionnaires were obtained. A significant relationship was found between
      parental rearing patterns and self-consciousness in adolescents with cleft lip
      and palate. A positive correlation was also observed between the scores of self
      evaluation, self-confidence, others' evaluation and psychological endurance,
      interpersonal relationship, and parent-child relationship of adolescents with
      cleft lip and palate and the scores of their parents' emotional care. Confidence
      was negatively correlated with the scores of parents' refusal to deny,
      punishment, and severity. CONCLUSIONS: Good parental rearing patterns play a
      critical role in establishing self-confidence, improving social adaptability, and
      maintaining interpersonal and parent-child relationship. Parents should give much
      care while avoiding refusal, denial, and punishment.

PMID- 30182568
TI  - [Stromal cell-derived factor-1 inducing metastasis squamous cell carcinoma of
      head and neck induced via integrin alphanubeta3-CXC chemokine receptor 4/7
      biological axis].
AB  - OBJECTIVE: To observe the influence of LM609/AMD3100/CCX754 on chemotactic
      capability, cytoskeleton, and expression of integrin alphanubeta3 protein of
      squamous cell carcinoma of head and neck (SCCHN) cell line PCI-13 induced by
      stromal cell-derived factor-1 (SDF-1) in vitro. METHODS: Migration assays, flow
      cytometry and immunofluorescence were used to observe the effects of SDF-1,
      LM609, AMD3100 and CCX754 on the migration, cytoskeleton and the expression of
      integrin alphanubeta3 protein in PCI-13 cell lines. RESULTS: SDF-1 favored PCI-13
      cell migration, pseudopod formation, and activities of integrin alphanubeta3
      phosphorylation. LM609, AMD3100, and CCX754 blocked all these effects.
      CONCLUSIONS: SDF-1 can induce metastatic SCCHN by integrin alphanubeta3-CXC
      chemokine receptor (CXCR) 4/CXCR7 axi. LM609, AMD3100, and CCX754 and can reduce
      the regulation of SDF-1 on SCCHN activity.

PMID- 30182569
TI  - [Role and mechanism of Galectin-3 gene in proliferation, invasion, and apoptosis
      of oral squamous cell carcinoma].
AB  - OBJECTIVE: The effect and mechanism of Galectin-3 gene expression on
      proliferation, invasion, and apoptosis of oral squamous cell carcinoma (OSCC)
      were investigated. METHODS: Reverse transcription-polymerase chain reaction (RT
      ?PCR) and Western blotting were used to detect the mRNA and protein of Galectin-3
      gene in OSCC. OSCC Tca8113 was divided into control, negative control, and
      Galectin-3 transfection groups. Western blotting was used to detect the
      expression of Galectin-3, matrix metalloproteinase (MMP)-2, MMP-9, Cleaved
      Caspase-3, beta-catenin, and Cyclin D1 protein after transfection for 48 h in
      each group. Cell proliferation was detected by CCK8. Cell invasion ability was
      detected by using a Transwell chamber. Cell apoptosis was detected by flow
      cytometry. RESULTS: The mRNA and protein expression levels of Galectin-3 gene in
      OSCC were significantly higher than those in adjacent tissues (P<0.01). Galectin
      3 protein expression in Tca8113 cells significantly decreased after RNA
      interference. Cell survival rate and invasion as well as MMP-2, MMP-9, beta
      catenin, and Cyclin D1 protein expression were significantly lower than the blank
      group. Apoptosis rate and Cleaved Caspase-3 protein expression were significantly
      higher than the control group (P<0.01). CONCLUSIONS: Inhibition of Galectin-3
      gene expression in OSCC can significantly reduce the proliferation and invasion
      of cancer cells and induce apoptosis. The mechanism is related to downregulation
      of the Wnt/beta-catenin signaling pathway.

PMID- 30182570
TI  - [Systematic retrospective study of oral cancer-related quality of life scale].
AB  - OBJECTIVE: The quality of life (QOL) related to oral cancer has recently become a
      focus of clinical studies. This study aims to systematically review the current
      research situation of QOL of local and foreign oral cancer patients and explore
      the existing related problems and future research directions to provide
      references and solutions. METHODS: Through relevant key words, PubMed, Wiley
      InterScience, Science Direct, CNKI, and Wanfang databases were first searched.
      The related target literature from 2000 to 2017 were screened. Finally, the
      frequency of oral cancer related to QOL scale used in literature was calculated,
      and the related scales were briefly introduced. RESULTS: From the target
      literature, 218 English target literature, 55 Chinese target literature, 24
      English scales, and 12 Chinese scales were selected. The most widely used scales
      for assessing the QOL of patients with oral cancer were as follows: University of
      Washington Quality of Life Questionnaire (UW-QOL), European Organization for the
      Research and Treatment of Cancer Quality of Life Questionnaire Core 30/Head and
      Neck 35 (EORTC QLQ-C30/H&N35), 36-Item Short-Form Health Survey (SF-36),
      Functional Assessment of Cancer Therapy-Head and Neck (FACT-H&N), and Oral Health
      Impact Profile (OHIP). CONCLUSIONS: The QOL related to oral cancer was well
      underway, and the study of geographical distribution was widespread. However, the
      work on self-developed scale remains inadequate. UW-QOL, EORTC QLQ-C30/H&N35, and
      FACT-H&N can be utilized as the preferred scales for evaluating the QOL of oral
      cancer patients. A specific disease-related function scale can also be selected
      according to specific research objectives.

PMID- 30182571
TI  - [Efficacy of minocycline hydrochloride combined with flap surgery for chronic
      periodontitis: a Meta-analysis].
AB  - OBJECTIVE: This study aimed to evaluate the efficacy of 2% minocycline
      hydrochloride combined with flap surgery in the treatment of chronic
      periodontitis. The superiority of this therapy to simple flap surgery was also
      explored. METHODS: We searched the databases of CNKI, VIP, Wanfang, Chinese
      Biomedical Literature, PubMed, ScienceDirect, and Embase from inception to July
      2017. Two reviewers independently screened literature, extracted data, and
      evaluated the bias risk of included studies. Then, Meta-analysis was performed
      using RevMan 5.3 software. RESULTS: A total of seven randomized controlled trials
      involving 217 patients were included. Meta-analysis showed that, in two groups,
      the changes in probing depth (PD) [MD=-0.55, 95%CI (-0.84, -0.26), P=0.000 2] and
      plaque index [MD=-0.08, 95%CI (-0.15, -0.01), P=0.03] at 3 and 6 months of PD
      [MD=-0.62, 95%CI (-1.04, -0.21), P=0.003] had statistically significant
      difference (P<0.05). The clinical attachment loss (CAL) [MD=-0.21, 95%CI (-0.47,
      0.04), P=0.10] had no statistically significant difference after 3 months
      (P>0.05), but the improvement in CAL was significantly improved by minocycline
      hydrochloride combined with flap therapy. CONCLUSIONS: Periodontal flap combined
      with minocycline adjuvant therapy for chronic periodontitis is effective in short
      term observations.

PMID- 30182572
TI  - [Dental care utilization of immigrants in Chengdu, China].
AB  - OBJECTIVE: This study considered Chengdu, Sichuan, China as an example to
      investigate the dental service utilization by foreigners and its influencing
      factors. Results of the study can be referred by dental practitioners to explore
      international development of dental services and can be provided for health
      policy makers to formulate oral health policies for immigrants. METHODS: A simple
      random sampling method with a questionnaire was designed based on Anderson's
      health utilization model and "Oral Health Questionnaire for Adults" by the World
      Health Organization. Oral health condition, consciousness, and demographic data
      were collected. Binary Logistic regression and stratified analysis with SPSS 20.0
      were performed. RESULTS: A total of 654 immigrants repre-senting 75 countries
      participated in the study. Among all participants, 102 (15.6%) experienced dental
      problems while in residence in China but paid no visit to dentists. Female
      immigrants, who spent considerable time living in Chengdu, experienced oral
      problems in a year, used dental floss, and reported family members in Chengdu,
      were more likely to visit Chinese dentists. Participants who lived in Chengdu for
      at least 10.5 months were the threshold distinguishing differences in dental
      visits in the country. CONCLUSIONS: The policymakers in Chengdu should consider
      creating a convenient and conducive dental care environment for immigrants.
      Additional information related to urgent oral and routine care should be provided
      to short- and long-term living immigrants in China. Dental practitioners in China
      should also contemplate on collaborating with foreign dental insurance companies
      to ensure better dental care access for immigrant patients.

PMID- 30182573
TI  - [Indirect pulp therapy for deciduous teeth with deep caries lesions].
AB  - Deciduous teeth are the first dentition of humans and play an important role in
      children's physical and mental development. Dental caries are one of the most
      common oral diseases in children. According to the data of the World Health
      Organization, 60%-90% of school children worldwide develop dental caries. In
      China, dental caries of primary teeth feature high incidence and low rate of
      visits. Without timely treatment, the deep caries lesions of primary teeth can
      lead to teeth defect, pulpitis, apical periodontitis, and maxillofacial space
      infection. Moreover, the premature loss of deciduous teeth can cause malocclusion
      and eruption disorder of subsequent permanent teeth. These conditions all cause
      considerable effects on children's oral health and physical and mental
      development. Performing active and effective measures to treat deciduous teeth
      with deep caries lesions is important to maintain the integrity and normal
      physiological function of dentition and facilitate normal eruption of permanent
      teeth. The current situation of indirect pulp therapy in China was studied in
      this paper. Basic concepts, including indirect pulp capping, interim therapeutic
      restoration, partial caries removal, stepwise caries removal, and atraumatic
      restorative therapy, have been defined by consulting domestic and foreign
      literature. A theoretical basis for improving the clinical pathway of deciduous
      teeth with deep caries lesions is provided by explaining the technical
      connotation and therapeutic importance of indirect pulp therapy in primary teeth.

PMID- 30182574
TI  - [Research progress on chitosan composite scaffolds in bone tissue engineering].
AB  - Bone tissue engineering is a scientific field devoted to the development of
      materials that can repair or replace human bone tissue with biological and
      engineering methods. The stent, which provides structural support and adhesion
      sites for cell and tissue growth, is one of the key elements in tissue
      engineering. The scaffold may comprise metal, polymer, and ceramic biomaterial.
      The polymer scaffold is widely used due to its biocompatibility,
      biodegradability, and mechanical stability. Chitosan, as a natural polymer, is
      derived from chitin and has played a particularly important role in bone tissue
      engineering over the past two decades. In recent years, chitosan composites and
      their application in bone tissue engineering have received considerable attention
      due to their small foreign body reaction, excellent antibacterial properties,
      plasticity, suitability for inward cell growth, and bone conduction. This review
      will discuss the biocompatibility and osteogenesis research in vivo and in vitro
      of several common chitosan composites in bone tissue engineering.

PMID- 30182575
TI  - [Research progress in pulpless posterior tooth restored with ceramic onlay].
AB  - Minimal invasive restoration is a common technique in the restoration of pulpless
      posterior teeth. The development of bonding techniques and ceramic materials in
      recent years has increased the use of high-strength ceramic onlay in the
      restoration of endodontically treated posterior teeth because of its minimal
      invasiveness, improved aesthetics, and low requirement of mechanical retention.
      This study conducts a retrospective analysis on the material, tooth preparation,
      bonding, and clinical considerations of ceramic onlay in endodontically treated
      posterior tooth.

PMID- 30182576
TI  - [Application of artificial intelligence in stomatology treatment and nursing].
AB  - Currently, artificial intelligence technology is being developed rapidly and is
      used in many clinical areas, especially in stomatology. The application of
      artificial intelligence technology in stomatology is a new technological
      revolution. This study focuses on artificial intelligence and its application
      status. The advantages, current situation, and development prospect of the
      application of artificial intelligence technology in stomatology treatment and
      nursing, such as oral and maxillofacial surgery, implant, prosthetics,
      orthodontics, oral medicine therapy, guidance, and teaching, are provided.

PMID- 30182577
TI  - [Gardner syndrome with chronic osteomyelitis of the jaw: a case report].
AB  - Gardner syndrome is a rare autosomal dominant disease. Its symptoms include
      multiple intestinal polyps, soft tissue tumors, dental disorders, osteoma, and
      congenital hypertrophy of the retinal pigment epithelium. Here, we present a
      patient with Gardner syndrome and chronic osteomyelitis of the jaw to highlight
      the serious damage that can be caused by Gardner syndrome.

PMID- 30182578
TI  - [Multiple pregnancy epulides: a case report].
AB  - Pregnancy epulis is a tumor-like lesion that results from aggravating gingivitis
      due to high level of gonadal hormone concentration. Pregnancy epulis is commonly
      manifested as a single lump. A case of multiple pregnancy epulises, which has
      been rarely explored, is reported in this paper. The patient received no other
      treatment but a single supragingival scaling. Results showed no remarkable
      changes in the lesion. However, all the epulides regressed spontaneously in five
      months after the parturition.

PMID- 30182579
TI  - Aberration correction method based on double-helix point spread function.
AB  - Point spread function (PSF) engineering has met with lots of interest in various
      optical imaging techniques, including super-resolution microscopy, microparticle
      tracking, and extended depth-of-field microscopy. The intensity distributions of
      the modified PSFs often suffer from deteriorations caused by system aberrations,
      which greatly degrade the image contrast, resolution, or localization precision.
      We present an aberration correction method using a spiral-phase-based double
      helix PSF as an aberration indicator, which is sensitive and quantitatively
      correlated to the spherical aberration, coma, and astigmatism. Superior to the
      routine iteration-based correction methods, the presented approach is iteration
      free and the aberration coefficients can be directly calculated with the measured
      parameters, relieving the computing burden. The validity of the method is
      verified by both examining the intensity distribution of the conventional
      Gaussian PSF in three dimensions and observing muntjac skin fibroblast cells.
      This iteration-free correction method has a potential application in PSF
      engineering systems equipped with a spatial light modulator.

PMID- 30182580
TI  - Review of clinical approaches in fluorescence lifetime imaging ophthalmoscopy.
AB  - Autofluorescence-based imaging techniques have become very important in the
      ophthalmological field. Being noninvasive and very sensitive, they are broadly
      used in clinical routines. Conventional autofluorescence intensity imaging is
      largely influenced by the strong fluorescence of lipofuscin, a fluorophore that
      can be found at the level of the retinal pigment epithelium. However, different
      endogenous retinal fluorophores can be altered in various diseases. Fluorescence
      lifetime imaging ophthalmoscopy (FLIO) is an imaging modality to investigate the
      autofluorescence of the human fundus in vivo. It expands the level of
      information, as an addition to investigating the fluorescence intensity, and
      autofluorescence lifetimes are captured. The Heidelberg Engineering Spectralis
      based fluorescence lifetime imaging ophthalmoscope is used to investigate a 30
      deg retinal field centered at the fovea. It detects FAF decays in short [498 to
      560 nm, short spectral channel (SSC) and long (560 to 720 nm, long spectral
      channel (LSC)] spectral channels, the mean fluorescence lifetimes (taum) are
      calculated using bi- or triexponential approaches. These are meant to be
      relatively independent of the fluorophore's intensity; therefore, fluorophores
      with less intense fluorescence can be detected. As an example, FLIO detects the
      fluorescence of macular pigment, retinal carotenoids that help protect the human
      fundus from light damages. Furthermore, FLIO is able to detect changes related to
      various retinal diseases, such as age-related macular degeneration, albinism,
      Alzheimer's disease, diabetic retinopathy, macular telangiectasia type 2,
      retinitis pigmentosa, and Stargardt disease. Some of these changes can already be
      found in healthy eyes and may indicate a risk to developing such diseases. Other
      changes in already affected eyes seem to indicate disease progression. This
      review article focuses on providing detailed information on the clinical findings
      of FLIO. This technique detects not only structural changes at very early stages
      but also metabolic and disease-related alterations. Therefore, it is a very
      promising tool that might soon be used for early diagnostics.

PMID- 30182581
TI  - Early detection of virus infection in live human cells using Raman spectroscopy.
AB  - Virus infection of a human cell was determined only 3 h after invagination. We
      used viral vector Ad-CMV-control (AdC), which lacks the E1 gene coding for early
      polypeptide 1 (E1). AdC can replicate in human embryonic kidney 293 (HEK293)
      cells into which the E1 gene has been transfected. According to partial least
      square regression discriminant analysis, it was assumed that two kinds of
      reaction take place in the cell during viral invasion. The first response of the
      cell was determined 3 h after the virus invasion, and the second one was
      determined ~9  h later. The first one seems to be due to compositional changes in
      DNA. Analysis of large-scale datasets strongly indicated that the second reaction
      can be attributed to a reduction in protein concentration or uptake of
      phenylalanine into the nucleus.

PMID- 30182582
TI  - [Effects of fire severity and recovery time on organic carbon content of forest
      soil in Great Xing'an Mountains, China.]
AB  - Fire is one of the major factors that alter structure and function of forest in
      the Great Xing'an Mountains, with consequences on soil carbon cycling in forests.
      In this study, we collected soil samples (layers O, A, AB, BC, and C) under
      different fire-severity levels (low, moderate, and high) and post-fire recovery
      times (1987-2012) in the forests of Great Xing'an Mountains. Analysis of variance
      and multiple comparison were used to analyze effects of fire severity and reco
      very time on content of soil organic carbon. The results showed that soil organic
      carbon (SOC) content in layer O presented a rising trend under both moderate- and
      high-severity fire disturbances. The content of SOC in layers A and B decreased
      year by year under low- and moderate-severity fires, which ranked in the order: 3
      years > 5 years > 10 years > over 10 years since fire. The content of SOC under
      high-severity fire presented an increasing trend within 10 years since fire
      distur-bance and then decreased rapidly over 10 years. The content of SOC in
      layer BC presented no obvious changes.

PMID- 30182583
TI  - [Monitoring and evaluation of the effects of Grain for Green Project in the upper
      and middle reaches of China's Yangtze River.]
AB  - Based on the comprehensive interpretation of GIS, we analyzed the normalized
      vegetation index (NDVI), land use types and digital elevation model (DEM), and
      revealed the results achieved by the Grain for Green Project in 84 prefecture
      level regions in the middle and upper reaches of the Yangtze River. The results
      showed that the NDVI was growing in this area from 2000 to 2015. Compared with
      2000, 2.1% of the farmland was no longer cultivated. 25% of the farmland with
      slope more than 35 degrees , and 2.7% of the farmland with the slope of 25
      degrees  to 35 degrees , and the most part of moderate slope farmland had been
      converted. Arable land was mainly converted to woodland and grassland. The
      coverage of forest and grassland significantly increased, with an enhancement of
      21.9%. The land area of low vegetation coverage was greatly reduced. The area
      with vegetation coverage less than 10% decreased by 95.3%, while the land area of
      high vegetation coverage significantly increased. The soil erosion intensity
      generally reduced. The land area with mild, strong, extremely strong soil erosion
      grade were all reduced by more than 10%, whereas severe soil erosion had not been
      alleviated. The proportion of forest coverage was 60% in this area. The magnitude
      of vegetation coverage changes varied in different periods. The spatial
      distribution was uneven, with higher coverage in the east than in the west. More
      works are needed to strenthen the management of Grain for Green Project in this
      area.

PMID- 30182584
TI  - [Effects of carbon and nitrogen additions on soil organic C, N, P contents and
      their catalyzed enzyme activities in a grassland.]
AB  - Soil organic C, N, P contents and their catalyzed enzyme activities play an
      important role in maintaining and supplying energy and nutrient in grasslands.
      There is no consensus on the effects of N deposition on soil organic nutrients
      and enzyme activities in grassland ecosystems. It remains unclear whether C
      addition will retard the negative effects of N deposition. We carried out an
      experiment in Hulun Buir grassland of Inner Mongolia to examine the effects of C
      and N additions on soil organic C, N, P and relative enzyme activities after
      three years treatments. The experiment was conducted with N treatments at five
      levels (0, 25, 50, 100 and 200 kg.hm-2.a-1) and with C treatments at three levels
      (0, 250 and 500 kg.hm-2.a-1). The results showed that higher levels of N addition
      significantly decreased dehydrogenase (DHA) and beta-1,4-N-acetylglucosaminidase
      (NAG) activities by 22.3% and 12.5%, respectively. Nitrogen addition had no
      significant effect on soil organic N and decreased the organic C and P contents
      by 6.6% and 14.5%, respectively. High C addition significantly increased DHA,
      beta-glucosidase (BG) activities and increased soil organic N and organic P by
      15.1%, 12.2%, 1.9%, 2.6%, respectively. The results suggested that continuous N
      inputs inhibited microbial activities and caused losses of soil organic C and
      organic P. Carbon addition could enhance microbial activities and promote the
      secretion of enzymes and increase soil organic N and P. The combined C and N
      addition could play an important role in maintaining the balance and supply of
      soil C, N, and P in grassland ecosystem.

PMID- 30182585
TI  - [Effects of balanced fertilization on growth and fruit quality of 'Huang-guan'
      pear on desert area.]
AB  - A field experiment was carried out to study the effects of balanced fertilization
      on growth and development, yield, fruit quality and mineral content in 'Huang
      guan' pear to provide a theoretical basis for the reasonable level of
      fertilization in pear orchards. Four treatments were arranged with 12-year old
      'Huang-guan' pear trees from the same orchard: conventional fertilization (CK),
      low levels of N, P2O5 and high level of S (T1), medium levels of N, P2O5 and S
      (T2), high levels of N, P2O5 and low level of S (T3). The results showed that
      different treatments had little effect on the growth and development of current
      year branch and leaves in the first year. However, in the se-cond year, T1
      treatment promoted the length and diameter of current-year branch by 16.2% and
      11.4%, respectively. Continuous fertilization could increase the leaf mineral
      contents in different degrees. The contents of Cu, Fe, and Zn in leaves under T1
      treatment, Mg and B in leaves under T2 treatment, and P and Mn in leaves under T3
      treatment were highest. Different fertilization levels had no significant effect
      on yield but on fruit quality. The contents of soluble sugars and vitamin C (Vc)
      were significantly increased by T2 treatment, which was 4.2% and 7.1% higher than
      those in CK. However, T1 significantly decreased contents of total soluble solid,
      soluble sugars and Vc, while highest organic acid content presented in T3. Fruit
      Fe content was positively correlated with soluble sugar content and fruit shape
      index, but was negatively correlated with single fruit mass, organic acids and
      Vc. Fruit P content was positively correlated with fruit shape index and
      firmness, but was negatively correlated with contents of soluble sugars, organic
      acids and Vc. Accordingly, T2 could improve fruit quality and maintain the
      productivity, and thus should be the suitable fertilization strategy for the
      'Huang-guan' pear management in desert area.

PMID- 30182586
TI  - [Effects of drought and rewatering on leaf photosynthesis, chlorophyll
      fluorescence, and root architecture of citrus seedlings.]
AB  - Drought severely affects citrus growth and development. In order to explore the
      mechanism of drought response of citrus, two cultivars (Sanhuhongju and
      Sanhuhuahong) that differing in drought tolerance were used as materials. The
      drought and rewatering treatment was conducted in pot experiments, with leaf
      photosynthesis, chlorophyll fluorescence, and root architecture being measured.
      The results showed that drought significantly decreased net photosynthetic rate
      (Pn), stomatal conductance (gs), transportation rate (Tr), and intercellular CO2
      concentration (Ci) of both cultivars, but Sanhuhongju generally showed less
      reduction. After rewatering, photosynthetic parameters were partly recovered but
      still lower than that in control. The water use efficiency (WUE) of Sanhuhongju
      was significantly increased after drought stress for 15 d, but the WUE of
      Sanhuhuahong was decreased except at the 15 day of drought stress. In addition,
      the maximum photosynthesis efficiency of PS II (Fv/Fm) was increased in both
      cultivars, but the photochemical quantum yield of PS II [Y(II)] was increased in
      Sanhuhuahong under drought. Both the apparent electron transport rate (ETR) and
      photochemical quenching (qP) were inhibited in the treated seedlings. The non
      photochemical quenching (NPQ) was decreased in Sanhuhongju while increased in
      Sanhuhuahong under drought and rewatering conditions. Drought stress resulted in
      the decrease of root surface area and volume of both cultivars, and it inhibited
      root elongation of Sanhuhuahong while improved the root length and root tip
      number of Sanhuhongju. The length of first lateral roots of Sanhuhongju was
      increased after drought stress 10 d, but did not change at the drought stress
      prophase of Sanhuhuahong, and then significantly decreased after 20 d.
      Furthermore, drought stress inhibited all lateral roots development except the
      tertiary lateral root of Sanhuhongju, and root growth could not be recovered by
      rewatering except root tip number. In conclusion, Sanhuhongju showed less
      reduction in leaf photosynthesis than Sanhuhuahong, with higher WUE and light use
      efficiency under drought stress. The increases of root tip number and lateral
      root length would help improve water uptake ability in Sanhuhongju.

PMID- 30182587
TI  - [Effects of nitrogen fertilizer application on carbon dioxide emissions from
      soils with different inorganic carbon contents.]
AB  - The application of nitrogen (N) fertilizer results in decreases of soil pH, but
      its effects on CO2 emission from soils with different inorganic carbon contents
      remain unclear. An closed-jar incubation experiment was conducted to examine the
      effects of N fertilizer and nitrification inhibitor (DCD) on soil pH and CO2
      emissions from three soil types with different contents of soil inorganic carbon
      (SIC), including paddy soil (PS), lime concretion black soil (CS), and eum-orthic
      anthrosols (AS). There were three treatments for each soil type, including
      control (N0), 0.2 g.kg-1 N fertilizer (N0.2), and its combination with DCD
      (N0.2+DCD). Soil pH, contents of mineral N (NH4+, NO3-), and CO2 emissions were
      measured. The results showed that N fertilizer addition significantly reduced
      soil pH and increased soil CO2 cumulative emissions in each type of soil.
      Compared to control, the CO2 cumulative emissions after 49 days incubation from
      the three soil types were enhanced by 39.4%, 23.4%, and 71.8% for PS, CS, AS
      soils, respectively. The soil pH of N0.2+DCD for three soil types were
      significantly higher than N0.2 after 49 days incubation, indicating that DCD
      application inhibited soil nitrification process. There were no significant
      differences in the mean CO2 cumulative emissions of PS and CS soils between N0.2
      and N0.2+DCD treatments; however, N0.2+DCD treatment significantly reduced
      cumulative CO2 emissions from AS soil by 12.5%. Soil inorganic carbon can
      effectively buffer soil acidification caused by N fertilizer addition. The CO2
      emission in calcareous soil following N addition is not only derived from the
      mineralization of soil organic carbon, but also from the dissolution of inorganic
      carbon. Given the large differences in soil inorganic carbon content in different
      regions of China, the problem of soil acidification and soil inorganic carbon
      pool consumption caused by long-term large amount of N fertilizer inputs deserve
      more attention.

PMID- 30182588
TI  - [Effects of conservation tillage on soil water condition and winter wheat yield
      in farmland].
AB  - Conservation tillage is one of the most important agricultural management
      measures on soil water conservation and crop yield increments. Based on long-term
      experiment during 2011 to 2016, effects of different tillage treatments,
      including conventional tillage, no-tillage and subsoiling treatments, on soil
      water condition, crop yield and water use efficiency were analyzed. The results
      showed that the average and relative soil water conservation rate was 7.3% and 
      0.68% at jointing stage of winter wheat under no tillage and subsoiling
      treatments, respectively. Compared with conventional tillage, soil water storage
      significantly increased in 0-60 cm soil layer at jointing stage of winter wheat
      under no-tillage. Besides, the mean values of soil water content significantly
      increased in 0-100 cm soil layer at jointing, flowering, filling, and harvesting
      stages under no tillage treatment while that was not significantly increased at
      jointing stage under subsoiling treatment. Furthmore, no-tillage treatment
      significantly increased the yield and water use efficiency of winter wheat,
      especially in the dry years. Therefore, soil moisture conservation ability and
      yield increment of no tillage was better than that of the subsoiling treatment in
      dry years.

PMID- 30182589
TI  - [Optimum nitrogen application rate to maximum yield and environment protection
      for winter wheat in Weibei dryland, China.]
AB  - To get the optimum nitrogen (N) fertilization rate which could guarantee wheat
      yield and protect environment, we examined wheat yield, N use efficiency,
      apparent N loss and soil N balance in Weibei dryland with a 3-year field
      experiment. The results showed that annual wheat yield increased and then
      decreased as N application rate increased in all the years with different annual
      rainfall, but the cumulative apparent N use efficiency significantly decreased.
      Higher yield and N use efficiency were obtained at the fertilization rate of 150
      kg.hm-2. Residual nitrate-N concentrations significantly increased with the
      increases of N application rate. When the N application rate was between 75 and
      150 kg.hm-2, the apparent N loss and loss rate were nearly the same, but if N
      application rate was higher than 150 kg.hm-2, the apparent loss and loss rate
      significantly increased. In conclusion, N application rate at 150 kg.hm-2 in
      Weibei dryland could guarantee high yield and N use efficiency, and
      simultaneously maintain residual nitrate-N concentration and reduce apparent N
      loss.

PMID- 30182590
TI  - [Effects of wide-range planting on the yield and nitrogen use efficiency of
      winter wheat cultivar Tainong 18.]
AB  - The effects of wide-range planting (WR) versus drilling-planting (DP) on grain
      yield, nitrogen use efficiency (NUE), and nitrogen uptake efficiency (UPE) were
      investigated using winter wheat cultivar Tainong 18 at experimental fields in
      Tai'an and Yanzhou during the growing seasons of 2015 and 2016. The results
      showed that planting pattern, experimental field location, and their interaction
      significantly affected the grain yield, NUE, and related indices of cultivar
      Tainong 18. Compared to DP, the WR pattern significantly increased grain yield by
      22.5% and 15.4% at Tai'an and Yanzhou, respectively, by raising the number of
      spikes per unit area at maturity (originating from the greater numbers of tillers
      per plant and per unit area) and the number of spikes per plant. Compared to DP,
      the WR pattern significantly increased UPE by 27.7% and 17.5% at Tai'an and
      Yanzhou, respectively. NUE with the WR pattern at Tai'an and Yanzhou was also
      increased, respectively, by 22.5% and 15.4% by enhancing nitrogen accumulation
      and increasing the UPE. A stonger positive effect on yield was observed at Tai'an
      than at Yanzhou. Thus, the popularization and application of a WR pattern would
      synergistically improve grain yields and NUE in winter wheat.

PMID- 30182591
TI  - [Effects of dark induced senescence on the function of photosystem II in flag
      leaves of winter wheat released in different years.]
AB  - Cultivar renewing is important for the increases of wheat yield. Studying changes
      of different physiological characteristics in the succession process of wheat
      varieties has great implications for future breeding. The senescence rate of flag
      leaf is a key factor affecting winter wheat yield. The variation of photosystem
      II function during senescence of flag leaves of wheat from different ages is
      still not clear. 31 wheat varieties planted in Henan Province from different ages
      since 1941 were examined in this experiment. The variation of photosystem II
      function was analyzed through measu-ring the relative chlorophyll content, and
      chlorophyll fluorescence induction dynamics during the senescence of flag leaves
      which were induced by continued dark. The results showed that the chlorophyll
      content of flag leaves was gradually increased in the succession of winter wheat.
      The chlorophyll degradation rate in the leaves of modern varieties was lower than
      the earlier varieties during the senescnece of flag leaves. Meanwhile, J point of
      the fluorescence induction kinetics curves in flag leaves of modern varieties
      increased less than I point. The photosystem II maximum photochemical efficiency
      and the amount of active reaction centers per unit area gradually increased
      during succession of wheat varieties, but the reduced extent in leaves of modern
      varieties was lower than that in the earlier ones. There was no significant
      correlation between the change of chlorophyll content and Fv/Fm in senescent
      leaves. There was significant positive correlation when the leaves aging degree
      increased, with the slope of trend line gradually increased. The photosystem II
      unit area and the amount of active reaction center was positively related with
      the aging degree, and both the correlation degree and slope of trend line
      increased with the increases of senescence extent of the leaves. The results
      suggested that chlorophyll content of flag leaf increased and the degradation
      rate slowed down gradually during the succession of wheat varieties. The anti
      aging ability of photosynthetic electron transfered from QA to QB was improved,
      which contributed to the slowing down of the decline of Fv/Fm and the amount of
      active reaction center. The increased chlorophyll content and anti-aging ability
      of photosystem II also contributed to the increases of yield in the succession of
      winter wheat.

PMID- 30182592
TI  - [Effects of microbial fertilizer on soil improvement and fruit quality of
      kiwifruit in old orchard.]
AB  - The continuous cropping obstacles caused by the increase of kiwifruit planting
      period resulted in imbalance of soil microbial community structure, and decrease
      of soil enzyme activity and physicochemical indicators, which substantially
      reduced both the quality and yield of kiwifruit. Under the field conditions, the
      traditional fertilization of fruit farmers was used as a control (CK) to study
      the effects of two different microbial fertilizers, JF and KF, which had been
      verified the growth promotion of kiwifruit aseptic seedlings test, on soil
      microbial community structure, soil enzyme activities, soil physicochemical
      characters during different growth periods of kiwifruit (germination period,
      florescence period, fruit enlargement period, fruit ripening period and next year
      germination period), as well as fruit quality. The results showed that both
      fertilizers significantly increased the ratio of bacteria with fungi and the
      ratio of actinomycetes with fungi in the kiwifruit orchard soil, indicating that
      they could improve and balance the soil microbial community structure. The
      enzymes activity in kiwifruit orchard soil with the addition of both fertilizers
      were significantly higher than that in CK, and among which sucrose, urease,
      phosphatase and polyphenol oxidase were increased by 17.9%-83.5%, 7.9%-83.0%,
      7.3%-45.4% and 8.1%-140.3%, respectively. JF and KF increased soil fertility (the
      concentrations of available nitrogen, phosphorus, potassium, total nitrogen,
      total phosphorus, total potassium, and organic matter content significantly
      increased) and decreased soil pH (a decrease of 0.29 to 0.34). After application
      of microbial ferti-lizer, the content of vitamin C, soluble sugar, soluble
      protein and other contents of kiwifruit increased, and the titratable acid
      content decreased. Therefore, the application of both fertilizers could balance
      soil microbial community structure, enhance soil fertility, and improve the fruit
      quality of kiwifruit. Our results provide robust theoretical basis for the
      application of microbial fertilizers in the old-aged kiwifruit orchards.

PMID- 30182593
TI  - [Effects of ditch-buried organic matter and irrigation amount after anthesis on
      the photosynthetic characteristics and yield of maize.]
AB  - Managements of organic matter and irrigation after anthesis will increase the
      capacities of water conservation and supply in maize field, with consequences on
      photosynthetic performance and yield under water-saving condition. We analyzed
      the gas exchange parameters and the performance of the photosystem 2 of ear
      leaves, and yield of maize cultivars Zhengdan 958, under three modes of ditch
      buried organic matter (no straw returned: M0, wheat straw returned: M1, mixtures
      of cow manure and wheat straw returned: M2) before seeding with two irrigation
      levels after anthesis (normal irrigation: W1, water-saving irrigation: W2). The
      results showed that M2 treatment significantly increased photosynthetic capacity
      and dry matter accumulation after anthesis compared with M1 treatment. Compared
      with water-saving irrigation, normal irrigation enhanced the photosynthesis of
      ear leaves. M2W1 treatment significantly increased net photosynthetic rate (Pn),
      stomatal conduc-tance (gs), transpiration rate (Tr), and performance of
      photosystem 2 (Phipo and omegao) of ear leaves after anthesis, while reduced
      intercellular CO2 concentration (Ci). In addition, M2W1 treatment significantly
      increased light utilization efficiency and maintained higher photosynthetic
      properties in ear leaves, and significantly increased dry matter accumulation and
      grain yield. Water-saving irrigation reduced photosynthetic performance of ear
      leaves, which declined the yield. But compared M2 with M0, water use efficiency,
      grain growth rate and yield increment under water-saving irrigation were higher
      than those under normal irrigation. Thus, mixtures of cow manure and wheat straw
      returned combined with normal irrigation could significantly increase
      photosynthetic properties of ear leaves and dry matter accumulation, which were
      the major reasons for yield enhancement. Importantly, the mixture of cow manure
      and wheat straw returned combined with water-saving irrigation could decrease the
      loss of crop yield resulted from lower irrigation.

PMID- 30182594
TI  - [Characteristics of soil nitrate accumulation and leaching under different long
      term nitrogen application rates in winter wheat and summer maize rotation
      system.]
AB  - Winter wheat and summer maize were the main crops in the North China Plain. While
      intensive farming system could generally achieve high yield, the perennial large
      amounts of nitrogen (N) fertilization application cause environmental problems
      including NO3--N accumulation and leaching at deep soil layer. Here, the effects
      of different N application rates on soil NO3--N accumulation and leaching in
      winter wheat-summer maize cropping system were investigated from 2010 to 2016 at
      Qingyuan County, Hebei Province, China. There were five treatments with N
      application rates at 0 (N0), 100 (N100), 180 (N180), 255 (N255) and 330 (N330)
      kg.hm-2. Results showed that crop yield and soil N status significantly varied
      among treatments for both wheat and maize after each harvest, respectively. Soil
      NO3--N were accumulated during winter wheat growing season and leached to deeper
      soil during summer maize growing season. Moreover, the soil NO3--N accumulation
      amount in the 90 to 180 cm soil profile decreased with the decreases of N inputs
      (N330 > N255 > N180 > N100 > N0). Soil NO3--N could be leached to 990 cm soil
      depth. There were six NO3--N accumulation peaks in the soil profile, with the
      peaks presenting at deeper soil profile with higher N fertilization rate. The
      deepest peak appeared at 840 cm soil depth with the N application rate of 330
      kg.hm-2. From the distribution of NO3--N accumulation in the soil profile, only
      around 10% of total NO3--N was accumulated between 0-90 cm soil depth, while the
      rest accumulated below 90 cm, which could not be largely absorbed by plants.
      Therefore, NO3--N leaching during summer maize growing season was serious and it
      was greater with higher N fertilization rate which might lead to increased risk
      of underground water contamination. In terms of balanced crop yield and soil NO3-
      N accumulation, the rate of 180 kg.hm-2 would be the optimum one in areas with
      similar cultivation and environmental conditions to the present study.

PMID- 30182595
TI  - [Effects of elevated atmospheric CO2 concentration on the stability of soil
      organic carbon in different layers of a paddy soil.]
AB  - It is vital to study the effects of elevated atmospheric CO2 concentration on the
      soil orga-nic carbon (SOC) stability in different soil layers for better
      understanding the mechanism of SOC transformation under the elevated atmospheric
      CO2 concentration. The paddy soil in a long-term FACE (Free Air Carbon-dioxide
      Enrichment) experiment was selected as the research object. Through the SOC
      physical fractionation and soil mineralization incubation, the effects of
      elevated atmospheric CO2 concentration on the soil organic carbon (SOC) content,
      particle organic matter (POM) content, SOC mineralization intensity, and enzyme
      activities were measured. Then, the effects of elevated atmospheric CO2
      concentration on the SOC stability in different layers were exa-mined. The
      results showed that the elevated atmospheric CO2 concentration had no significant
      effect on SOC content, but significantly increased the POM-C content by 93.7% and
      the invertase and polyphenol oxidase activities by 61.1% and 83.7% in the topsoil
      layer, respectively. These results indicated that SOC stability of topsoil was
      reduced under the elevated atmospheric CO2 concentration. However, the elevated
      atmospheric CO2 concentration had no significant effect on the SOC stability of
      deep soil layer. Our results would help assess the capacity of soil sequestrated
      and accumulated organic carbon and provide basis for scientific management of
      farmland under greenhouse effect in the future.

PMID- 30182596
TI  - [Effects of different nitrogen application rates on low temperature resistance of
      late rice at heading and flowering stage.]
AB  - Four levels of nitrogen application (N1, low nitrogen, 90 kg N.hm-2; N2, normal
      nitrogen, 180 kg N.hm-2; N3, high nitrogen, 250 kg N.hm-2; N4, ultra high
      nitrogen, 330 kg N.hm-2) were set to examine the effects of nitrogen application
      on the growth and development, yield formation and related physiological
      characteristics of late rice under low temperature condition during heading and
      flowering stage, with super hybrid late rice variety Wufengyou T025 as test
      material. The results showed that yield of all treatments decreased in different
      degrees under the low temperature conditions, with the yield of N2 being the
      highest, and N1 the lowest. The effective panicles per plant and total grains per
      panicle in N3 and N4 were higher than those of the other treatments, but their
      seed setting rate and harvest index were significantly decreased. With the
      increases of nitrogen application rates, pocketed panicle rate, the total dry
      mass and chlorophyll contents (SPAD value) increased to different extent, while
      the panicle dry mass of N2 was the highest. After low temperature, chlorophyll
      content, net photosynthetic rate and transpiration rate of the total treatments
      decreased to varying degrees, and the declined range of the net photosynthetic
      rate and trans-piration rate in N3 and N4 were higher than other treatments. The
      contents of free proline, malondialdehyde and peroxidase activity of all
      treatments increased to varying extent, while superoxide dismutase, catalyes
      activities and the soluble protein contents decreased, with the magnitude of
      variation in N3 and N4 being the greatest. It demonstrated that high amounts of
      nitrogen application were unfavorable to late rice to resist low temperature at
      heading and flowering stage and thus misuse of nitrogen fertilizer application
      should be avoided in production. The suitable amount of nitrogen application in
      double cropping late rice was not more than 180 kg.hm-2.

PMID- 30182597
TI  - [Effects of purified humic acid on the growth and nitrogen metabolism of cucumber
      seedlings under nitrogen stress.]
AB  - To investigate the effects of purified humic acid (PHA) on the growth and
      nitrogen metabolism of cucumber under different levels of nitrogen stress and to
      explore the mechanism of PHA's alleviation on abiotic stress, we examined the
      effects of PHA on 'Xintaimici' cucumber growth and nitrogen metabolism under low
      nitrogen (1.0 mmol.L-1 NO3-) stress and high nitrogen (101 mmol.L-1 NO3-) stress
      in hydroponics compared with normal level (11 mmol.L-1 NO3-). The results showed
      that the growth of cucumber seedlings was inhibited under nitrogen stress
      treatments. Plant height, stem diameter, leaf area and dry matter accumulation
      under nitrogen stress were lower than that at normal nitrogen level. Dry matter
      accumulation under the normal nitrogen level and low nitrogen stress were
      significantly increased by PHA, but there was no significant difference under
      high nitrogen stress. The absorption of NO3- in cucumber seedlings was affected
      by PHA, showing increased nitrate content in cucumber seedlings under low
      nitrogen stress and decreased under high nitrogen stress. PHA significantly
      decreased ammonium content in roots and leaves under low and high nitrogen
      stress. Compared with normal level of nitrogen (CK), NR, GS, GOGAT, GDH activity
      in roots and leaves and NiR activity in roots significantly decreased under low
      and high nitrogen stress. PHA increased the activities of NR, NiR, GS, GOGAT, and
      GDH to different extents. PHA increased amino acid and soluble protein content in
      cucumber seedling roots and leaves. In summary, PHA addition alleviated the
      inhibitory effect of nitrogen stress on the growth of cucumber seedlings.

PMID- 30182598
TI  - [Effects of soil salinity on Bt protein content and nitrogen metabolic physiology
      in boll shell of Bt cotton].
AB  - In order to clarify the effects of soil salinity on the insect-resistance of boll
      in transgenic Bt cotton, potted plants of two Bt cotton cultivars Xinmian 33B
      (salt-sensitive) and Zhong 07 (salt-tolerant) were exposed to five levels of soil
      salinity (0, 0.15%, 0.30%, 0.45% and 0.60%). The results showed that Bt protein
      content of boll shell decreased with increasing soil salinity. Compared with the
      control (0% soil salinity level), the Bt protein content of boll shell decreased
      significantly when the soil salinity level was above 0.15% for Xinmian 33B and
      above 0.30% for Zhong 07. The reduction extent of Bt protein content of boll
      shell at 30 days post anthesis (DPA) was greater than that at 10 DPA under the
      same soil salinity level. Significant reductions of soluble protein contents,
      nitrate reductase (NR), and glutamate pyruvate transaminase (GPT) activities were
      observed when the boll shell Bt protein content was significantly reduced. The
      content of free amino acid, protease, and peptidase activity of boll shell
      significantly increased when the soil salinity level was above 0.30%. In
      conclusion, soil salinity affected boll shell nitrogen metabolism and reduced Bt
      protein synthesis. Middle and high soil salinity levels could enhance
      decomposition of Bt protein, which further decreases the expression level of
      insecticidal protein.

PMID- 30182599
TI  - [Mechanism of reduced insecticidal protein expression in Bt cotton under high
      temperature and drought based on proteomics.]
AB  - To provide theoretical basis for the safety of insecticidal efficiency in Bt
      cotton, the effects of high temperature and drought stress on insecticidal
      protein expression and protein diffe-rently expression profile was studied. In
      this study, the Bt cotton cultivar Sikang 3 was used as expe-rimental material,
      with two treatments (40% field capacity and 38 C, HD, and 60% field capacity and
      32 C, CK). Differences in proteomics of Bt cotton between HD and CK were compared
      using label-free quantitative proteomics technology. The results showed that high
      temperature and drought caused a significant reduction of insecticidal protein
      content in bolls, with a decrease of 38.2 ng.g-1 FM. The analysis of differential
      protein expression by label-free quantitative proteomic approach showed that 83
      proteins were significantly up-regulated, but 104 proteins were significantly
      down-regulated in HD stressed cotton plants compared with CK. 122 new proteins
      were detected and 167 proteins expression was not observed under stressed
      conditions. Results from the enrichment analysis of differently expressed protein
      between two treatments showed that 14 KEGG (Kyoto Encyclopedia of Genes and
      Genomes) pathways were affected under stress. Three KEGG pathways were related to
      the Bt protein synthesis and degradation: carbohydrate digestion and absorption
      pathway, protein export pathway, and protein processing in endoplasmic reticulum
      pathway. In the carbohydrate digestion and absorption pathway, the starch
      hydrolysis ability of HD treated cotton plants increased, while the ability to
      phosphorylate the hexoses, fructose and glucose decreased. In protein export
      pathway, the peptide synthesis in HD treatment was not significantly affected,
      while the process of transferring peptides into the endoplasmic reticulum was
      prohibited. In the protein processing in endoplasmic reticulum pathway, the
      ability of ubiquitin mediated proteolysis was increased in HD treatment.

PMID- 30182600
TI  - [Spatial point patterns and their association dynamics of forest landscapes in
      Maoershan region, Northeast China between 1983 and 2016.]
AB  - Researches on the dynamics of spatial point patterns and their associations of
      forest landscape has important implications for maintaining forest stability and
      making forest management decisions. Based on the four period datasets of forest
      resource inventory in Maoershan region in 1983, 1993, 2004, and 2016, the O-ring
      statistics within Programita software (version 2010) was used to quantitatively
      analyze the dynamics of spatial point patterns and associations. The results
      showed that the cover percentage of soft-wood broadleaved mixed forest (SBM)
      significantly decreased, the percentage of natural Quercus mongolica (NMO)
      increased in the beginning, and then became lower. The percentage of hard
      broadleaved mixed forest (HBM), Larix gmelinii (RLG) and Pinus sylvestris var.
      mongolica (RPS) plantations increased dramatically from 1983 to 2016. During the
      study period, the scale of clumped distribution for the SBM, HBM, NMO all
      significantly decreased with the increasing spatial scale. The clumped
      distribution ranging from 0-7 km decreased to 0-3 km, and then tended to be
      random or uniform distribution with the further increases of spatial scale. The
      patterns of RLG showed aggregated distribution within the small scale and tended
      to be random or uniform distribution with the increasing scale. However, the
      range of scale of uniform distribution increased and random distribution
      decreased. The patterns of RPS showed clumped distribution within small scale (0
      4 km) and the range of scale tended to be larger. On the whole, the spatial
      association between most of the landscape types within the small scale showed
      negative association. With the increases of scale, these landscape types
      gradually become non-association or positive association. However, only a few
      landscape types (e.g. RLG and RPS in 1983) showed positive association in a small
      scale. With the increases of scale, all the relationship tended to be non
      association. The dynamics of the association of forest landscapes showed
      different regularity. The dynamics of spatial point patterns and associations of
      Maoershan region were the comprehensive results of the forest management during
      1983 and 2016.

PMID- 30182602
TI  - [Applicability of five drought indices for agricultural drought evaluation in
      Jilin Province, China.]
AB  - Drought is a severe meteorological disaster on agriculture in Jilin Province.
      Agricultural drought can be represented by drought indices, but there is no
      universal applicable index. It is of great significance to examine the
      applicability of drought indices for agricultural drought evaluation. Based on
      daily meteorological data, soil moisture data, and drought statistical
      information from 1961 to 2014, we selected typical drought years and typical
      drought zones. The applicability of five drought indices was evaluated, including
      precipitation anomaly percentage (PA), relative moisture index (MI), crop water
      deficit anomaly index (CWDIa), Palmer drought severity index (PDSI) and
      meteorological drought comprehensive index (MCI). The results showed that
      agricultural drought evaluation of MI was consistent best with drought
      information for two typical drought years of 1997 and 2007, followed by PA and
      MCI. For typical drought zones (Tongyu in the west, Lishu in the center and
      Helong in the east), MI and PDSI performed much better than other ones. During
      growing season, PA was more applicable in April, July and August, MI was
      applicable to April, May and September, CWDIa only performed well in May, PDSI
      could be an indicator to agricultural drought in June, July, August and
      September, MCI was useful in May, June, July and August. For different regions
      with agricultural drought, MI, PDSI and MCI were applicable in western region,
      PDSI in central region, and PA, PDSI and MCI were suitable for eastern region.

PMID- 30182601
TI  - [Spatial heterogeneity of soil hydrolase activities and their influencing factors
      in a typical Karst catchment of Guizhou Province, China.]
AB  - Soil enzyme activities are sensitive indicators of soil quality. However, their
      spatial hetero-geneity and the influencing factors are not well known. In this
      study, geostatistics, Kriging method, one-way ANOVA and correlation analyses were
      used to examine the spatial variability and influencing factors of activities of
      six soil hydrolases: beta-1,4-glucosidase (betaG), beta-1,4-xylosidase (betaX),
      cellobiohydrolase (CBH), beta-1,4-N-acetylglucosaminidase (NAG), leucine amino
      peptidase (LAP), and acid phosphatase (AP) in 0-10 cm soil layers in a karst
      catchment in Guizhou Pro-vince, China. The results showed that the activities of
      those soil hydrolase had different spatial hete-rogeneity. The optimal models
      were the spherical models for betaX, CBH and AP, the Gaussian model for betaG and
      NAG, and the exponential model for LAP, respectively. The spatial structure
      ratios C/(C0 +C) of betaG, betaX, CBH, NAG and LAP activities were 99.9%, 99.9%,
      99.9%, 76.3% and 96.6%, respectively, implying strong spatial autocorrelation and
      weak influence from topographic factors. The spatial structure ratio of AP
      activity was 50.0%, suggesting moderate spatial autocorrelation and vulnerable to
      the influences of random factors. The variation ranges of the hydrolase acti
      vities were greater than the sampling distance, indicating that the sampling
      methods could mirror spatial variability of the soil enzyme activities at a small
      watershed scale. Land use type significantly affected the activities of NAG and
      AP. Slope position significantly affected AP activity. The activity of AP was
      negatively correlated with soil pH, while the activities of other enzymes except
      NAG were positively correlated with soil pH. Our results provided useful
      information on the spatial distribution mechanism of soil hydrolase.

PMID- 30182603
TI  - [Landscape preference of different stakeholders in highly intensive farming
      agricultural landscape.]
AB  - Intensive agriculture is the way for production and management in modern
      agriculture, which increases the yield per unit area of farmland, brings a series
      of environmental and ecological problems, and limits the sustainability of
      agriculture. Landscape preference focuses on different stakeholders' preferences
      for landscape, reflects the influences of human's subjective feelings and
      behaviors on landscape. Based on the agricultural landscape of Fengqiu County in
      Henan Province, we investigated the characteristics of the landscape elements
      which stakeholders preferred and analyzed the reasons using the questionnaire
      survey and other related methods. We proposed several suggestions for future
      development of the agricultural landscape in study area. The results showed that
      stakeholders preferred the landscape element which is simple and easy to manage,
      and emphasized the production and economic functions of agricultural landscape.
      Experts and local environmentalists preferred the landscape elements with
      multiple functions and benefits, as well as complex landscape configurations with
      high heterogeneity, with the aim to develop the multifunctional agricultural
      landscape. Factors such as education level, professional background and types of
      intervie-wees had obvious influences on the landscape preference of stakeholders.
      The decision-making beha-vior of government, the degree of economic compensation,
      and the technological support of eco-agriculture would be the important factors
      determining the possible development of landscape structure and function in the
      future.

PMID- 30182604
TI  - [Emergy analysis of four typical planting modes in Karst faulted basins of Yunnan
      Province, China.]
AB  - Accurate evaluation of typical cropping patterns in faulted basins can provide
      scientific guidance for planting in the area. The planting modes of marigold,
      pomegranate, pomegranate+grass+sheep in Mengzi City of Yunnan Province were
      compared with the traditional corn planting mode. The ecological benefits and
      economy benefits of these rocky desertification control modes were analyzed by
      the method of emergy analysis. The environmental loading ratio (ELR) and emergy
      restoration ratio (ERR) were 13.80 and 0.41 in pomegranate planting mode,
      respectively, while 0.30 and -2.87 in marigold planting mode. The ecological
      benefits in pomegranate planting mode and marigold planting mode were lower than
      that of corn, and ELR and ERR were 1.30 and 4.64, respectively. However, the
      economic pure benefit per unit (EPBU) in pomegranate planting mode and marigold
      planting mode were 3.05 and 59.98 times of that in corn mode, respectively,
      indicating that pomegranate planting mode and marigold panting mode had higher
      economic benefits than that of corn. Pomegranate+pasture+sheep mode had the
      highest ecological and economic benefits among the four modes. The plus of
      forage+livestock subsystem to pomegranate planting mode had high eco-efficiency
      (ELR of 4.95, ERR of 0.63) and economic benefit (EPBU of 71.38 times than that of
      corn). Thus, we recommend that the local government should increase technical
      support for marigold planting mode and pomegranate+pasture+sheep mode, which
      including optimizing structures of fertilizer input, and crop cultivation and
      livestock breeding processes. Meanwhile, government could establish short-term
      labor markets for picking of fruits and flowers.

PMID- 30182605
TI  - [Influence of climate change on the suitable ranges for planting pickled mustard
      tuber in Chongqing.]
AB  - Pickled mustard tuber (Brassica juncea var. tumida) belonging to Cruciferae, is a
      unique economic crop in China. Climate is an important factor affecting the
      distribution of pickled mustard tuber. Based on species presence data at 279
      locations and 22 high-resolution environmental factor layers, we analyzed the
      potential planting area of pickled mustard tuber in Chongqing by MaxEnt model
      under the current conditions and the future distributions for the periods 2050s
      and 2070s under the climate change scenarios of RCP 2.6, RCP 4.5, RCP 6.0 and RCP
      8.5 described in the Special Report on Emissions Scenarios (SRES) of IPCC
      (Intergovernmental Panel on Climate Change). The results showed that MaxEnt model
      was excellent in predicting its potential plan-ting area. The cumulative
      contributions of dominant factors reached as high as 81.7%, including
      precipitation of wettest month, temperature annual range, minimum temperature of
      coldest month, isothermality, mean diurnal range and average maximum temperature.
      The threshold of those factors was 173-183 mm, 27.2-28.3 C, 1.8-3.8 C, 22.5-24 C,
      6.2-6.8 C and 14.8-18.0 C, respectively. Under current condition, the optimum
      suitable areas of pickled mustard tuber, which amounted to 4.2%, were in the
      northeast, west and east of Fuling, the east and south of Changshou, the south
      and southeast of Dianjiang, the northwest and north of Fengdu, the southeast of
      Zhongxian, and a small part of Wulong and Nanchuan, while the proportion of
      moderately suitable areas was 6.3%. Under four climate change scenarios, the
      optimum suitable areas would drop to 2.7%, 3.8%, 3.1%, 3.2% and 3.1%, 3.7%, 3.5%,
      2.9% for the periods 2050s and 2070s, respectively, while moderately suitable
      areas would rise gradually.

PMID- 30182606
TI  - [Evaluation and change of Danjiangkou Reservoir dynamic capacity.]
AB  - Dynamics of storage capacity of the Danjiangkou Reservoir have important
      significance to guarantee water diversion middle route project. Aiming at the
      problems of complexity in measurement and short-term fluctuation in capacity in
      Danjiangkou Reservoir, we chose remote sensing data of Landsat series and HJ
      1A/B, and DEM data, constructing a new method for extraction of dynamic storage
      capacity, extracting the monthly dynamic information of reservoir capacity in
      2000-2016. We analyzed the factors that caused the dynamic change of storage
      capacity and its impacts on water diversion. The results showed that, in the past
      17 years, the largest reservoir capacity of Danjiangkou was 19.216 billion m3 and
      the minimum was 7.974 billion m3, with an average of 11.204 billion m3. After the
      first phase of the middle route of south-to-north water transfer, the storage
      capacity of Danjiangkou Reservoir had been gradually increased. In terms of the
      monthly averages, the capacity from May to October increased gradually, from
      October through December showed fluctuate change, and decreased gradually from
      December to next May. The cyclical artificial storage and climate change were the
      driving forces for the changes of the storage capacity. The Danjiangkou Reservoir
      could meet the need for water transfer under the reasonable dispatching of the
      reservoir water.

PMID- 30182607
TI  - [Application of extreme value distribution theory in the forecast of chilling
      return periods of Guangdong Province, China.]
AB  - Chilling is the third weather disaster following flood and typhoon in Guangdong
      Province. Prediction of chilling return period is of practical significance for
      scientific reduction and protection of disaster. Four models, including Gumbel
      distribution, Weibull distribution, log-normal distribution and Peasron-III
      distribution, were applied, based on the chilling index, to fit the probability
      distribution of chilling extreme calculated by chilling accumulation for 86
      weather stations of Guangdong Province from 1961 to 2015 (December to the
      following February). The optimal models were selected to calculate the chilling
      extreme value of return periods. Results showed that Pearson-III distribution was
      the optimal model for 77 out of the 86 weather stations. The log-normal
      distribution was optimal for eight weather stations and Gumbel distribution was
      optimal for only one station. Weibull distribution was not suitable for modeling
      extreme value of Guangdong Province. Different return periods of 10-, 25-, 50-
      and 100-year were predicted by optimal distribution models respectively, with a
      relative error less than 6%. Chilling extreme for years presented obviously
      latitude distribution feature, with more in north side and less in south side,
      which matched the distributions of the lowest temperature, average temperature
      and temperature dipping scale during chilling period. Our results are useful for
      guiding the chilling defense for relevant industries in Guangdong Province.

PMID- 30182608
TI  - [Construction of ecological corridors in Changli County based on ecological
      sensitivity and ecosystem service values.]
AB  - Ecological corridors provide essential routes for biological migration, which
      would promote species exchange among different habitats. The construction of
      corridors is beneficial to alle-viate the damages caused by the fragmentation of
      landscapes due to the acceleration of urbanization, with significance to
      biodiversity conservation. In this study, we located the ecological sources with
      the results of ecological sensitivity evaluation and ecosystem service value
      analysis in Changli County based on its land use status in 2015. Then, we
      produced the potential corridors with the minimal cumulative resistance model
      (MCR) and the minimum cost path method, and identified the key corridors with the
      gravity model. We put forward the ecological corridor system including four
      important corridors and two general corridors to underpin the scientific
      knowledge for the ecological corridor construction project and biodiversity
      conservation. The results showed that the ecological sensitivity of this area was
      relatively moderate and ecosystem services value was relatively low. Both the
      ecological sensitivity and ecosystem services were lower in the middle area but
      higher in around areas. The ecological sources were mainly distributed in the
      northern Jieshi Mountain Scenic Area, the eastern coastal state-owned forest farm
      and the western water source conservation area, which were highly coincident with
      the nature reserves determined by Ecological Environment Construction and
      Protection Planning (2011-2030) in the study area. The total length of the
      corridors was 112.66 km, within which the length of important ones was 47.61 km
      and that of general ones was 65.05 km. The best width of the corridors was around
      30 to 60 m. The ecological corridors and ecological sources constituted an
      annular closed area, which would effectively promote species migration and the
      exchange of material and energy.

PMID- 30182609
TI  - [Assessment of aquatic ecological security for mountainous rivers: A case study
      in the Taizi River Basin, Northeast China.]
AB  - Watershed ecological security is strongly associated with the aquatic ecological
      status of the upper mountainous area. The present study aimed to assess the
      watershed ecological security status of the mountainous area under the PSFR
      (Pressure-State-Function-Response) assessment framework. An evaluation index
      system was established according to the watershed characteristics, which included
      four project hierarchical layers, i.e., aquatic ecological pressure, aquatic
      ecological state, ecological function, and social response, 11 component layers
      and 23 evaluation indexes. This index system was applied to evaluate the
      watershed ecological security status of the mountainous area (35 sub-watersheds)
      in the Taizi River Basin, Liaoning Province. Our results showed that the aquatic
      ecological status of the study area could be classified into three groups:
      insecure, general secure and secure, no very insecure and very secure status.
      Nine sub-watersheds were at the insecure ecological status, accounting for 25.7%
      of the total sub-watersheds, whereas 22 sub-watersheds were at the general secure
      state, representing 62.9% of the study area. In contrast, only four sub
      watersheds were grouped at the secure status. Furthermore, agricultural activity
      was identified as the most significant factor responsible for the aquatic
      ecological security of mountainous area in the Taizi River Basin. Habitat
      degradation, including water quality deterioration and habitat loss,
      significantly reduced the ecological functions of the Taizi River Basin, and
      decreases in rare and peculiar species and biodiversity also posed a threat to
      the ecological integrity of the study region. Our results could be applied to
      diagnose the major factors affecting aquatic ecological security, and provide
      information for effective ecological restoration.

PMID- 30182610
TI  - [oil microbial biomass and enzyme activities among different artificial forests
      in Ziwuling, Northwest China.]
AB  - Decades of ecological restoration on the Loess Plateau has achieved significant
      on-site benefits to reduce soil erosion and improve soil quality, with remarkable
      off-site effects of reducing sediment delivery to Yellow River. However, regional
      forest community succession is still far from being adequately developed. The
      Ziwuling forest region and its highly developed forest community, as an advanced
      eco-zone, can lend practical experience to other regions on the Loess Plateau and
      help to identify the most suitable tree species for a better regional restoration
      in the future. With the aim to systematically understand the potential effects of
      typical local tree species to soil properties, three typical and well-established
      artificial forests in the Ziwuling region, Robinia pseudoacacia, Pinus
      tabuliformis and Platycladus orientalis were investigated in this study, with the
      climax community Quercus wutaishanica as a reference. All the four forest type
      had comparable stand age (25 years). Soil samples from 0-20 cm layers were
      collected from those four plantations. The soil microbial biomass (carbon and
      nitrogen), soil enzyme (invertase, urease and alkaline phosphatase) activities
      and their correlations were measured and analyzed. The results showed that: 1)
      soil invertase activity ranged from 16.94 to 64.49 mg.g-1.24 h-1, the soil urease
      activity from 0.15 to 0.26 mg.g-1.24 h-1, and the alkaline phosphatase activity
      from 0.65 to 1.23 mg.g-1.24 h-1. The activities of those three enzymes were
      significantly higher in the P. orientalis soil that in the R. pseudoacacia and P.
      tabuliformis soils. The geometric average values in the P. orientalis soil were
      even greater than that in the Q. wutaishanica soil. 2) The soil microbial biomass
      carbon and nitrogen varied from 247.37 to 529.84 mg.kg-1 and 41.48 to 77.91 mg.kg
      1, respectively. Both of them were significantly greater in the P. orientalis
      soil than that in the R. pseudoacacia and P. tabu-liformis soils. Even though the
      soil microbial biomass carbon in the P. orientalis soil remained lower than that
      in the Q. wutaishanica soil, its soil microbial biomass nitrogen was greater than
      in the Q. wutaishanica soil. 3) The dissolved organic carbon and nitrogen in the
      P. tabuliformis soil were much greater than that in other species, even greater
      than their own soil microbial biomass carbon and nitrogen. Such a result
      indicated that dissolved organic matter might play a more important role in
      providing plant available nutrients than microbial biomass in the P. tabuliformis
      soil. 4) The microbial biomass carbon and nitrogen were significantly positively
      correlated with the total organic carbon and the total nitrogen, particularly for
      the R. pseudoacacia and P. tabuliformis soils. There were significantly positive
      relationships between the soil invertase activity, urease activity and alkaline
      phosphatase activity, and their soil organic carbon, total nitrogen and total
      phosphorus contents. 5) Based on the results of principal component analysis, we
      concluded that the artificial forests types had obvious effects on soil microbial
      carbon and nitrogen, soil organic carbon, total nitrogen, the ratio of carbon to
      phosphorus, the ratio of nitrogen to phosphorus and urease activity. Overall, our
      findings suggested that P. orientalis is better than R. pseudoacacia and P.
      tabuliformis in term of improving soil properties in the south forest zone on the
      Chinese Loess Plateau.

PMID- 30182611
TI  - [Influence of long-term enclosure and free grazing on soil microbial community
      structure and carbon metabolic diversity of alpine meadow.]
AB  - Soil microbial community structure and functional diversity have great
      implications for the maintenance of the function and stability of grassland
      ecosystem. We studied the variation of soil microbial community structure,
      community diversity of carbon metabolism and their driving factors between the
      long-term enclosure and the free grazing grasslands in Qinghai-Tibet Plateau by
      using phospholipid fatty acid and Biolog techniques. The results showed that: 1)
      there were significant differences in soil microbial community structure and the
      utilization of carbon source between the long-term enclosed and free grazed
      grasslands. 2) Long-term enclosure significantly increased the content of total
      PLFA, bacteria, fungi and actinomycetes. 3) Soil carbon metabolic activity,
      diversity and richness in free-grazing grassland was significantly higher than
      the enclosed grassland, but evenness showed an opposite pattern. 4) Compared with
      the free grazed grassland, long-term enclosure significantly increased the
      utilization of polymers, carbohydrates, carboxylic acids, and amines by soil
      microorganisms. 5) Results from the redundancy analysis showed that vegetation
      coverage significantly affected soil microbial community structure and carbon
      metabolism. The soil microbial content, carbon metabolism diversity and richness
      in the long-term enclosed grassland were higher than those of the free grazing
      grassland, indicating that long-term enclosure was more conducive to improve the
      diversity and carbon metabolism of soil microbial community.

PMID- 30182612
TI  - [Effects of different low limits of irrigation on nutrients, enzyme activity and
      glomalin-rela-ted soil protein in soil aggregates of drip irrigation under
      plastic film.]
AB  - Irrigation is the main source of soil water in greenhouse. There is a lack of
      understanding on the effects of drip irrigation under the plastic film on the
      distribution characteristics of soil nutrients, enzyme activity and glomalin
      related soil protein (GRSP) in soil aggregates. The effects of different
      irrigation low limits (20 kPa, D20; 30 kPa, D30; 40 kPa, D40) on soil organic
      carbon (SOC), total nitrogen (TN), total phosphorus (TP), urease activity,
      invertase activity and GRSP in soil aggregates were investigated under the
      greenhouse with the continuously six years' irrigation. The results showed that
      compared with D20 and D40 treatments, D30 treatment significantly decreased the
      proportion of micro-aggregate (<0.25 mm), increased the proportion of macro
      aggregate (>0.25 mm), and improved the mean mass diameter (MWD) by 26.4% and
      13.4%, respectively. The concentrations of SOC, TN, TP and GRSP were relatively
      higher in 2-1 mm, 1-0.25 mm, and <0.053 mm aggregates. About 46.5% of SOC, 53.3%
      of TN and 37.7% of TP were distributed in the 1-0.25 mm aggregates. The urease
      and invertase activities were increased with the decreases in the size of
      aggregates, which were significantly increased in D30 and D40 treatments. The 1
      0.25 mm aggregates had highest contributions to enzyme activities, with 38.7% of
      urease and 41.2% of invertase in bulk soil. Results from the correlation analysis
      showed that MWD was highly positively correlated with GRSP, SOC and urease
      activity, and the concentration of GRSP was highly positively correlated with SOC
      and urease activity. Therefore, the irrigation low limits of 30 kPa promoted soil
      aggregate stability and protection of soil aggregates to nutrients, enzyme
      activities and GRSP in greenhouse.

PMID- 30182613
TI  - [Responses of fungal community structure and functional group to fertilization in
      yellow clayey soil.]
AB  - We investigated the responses and underlying mechanisms of community composition,
      and function group of fungi in yellow clayey paddy soil to different long-term
      fertilization, which may provide scientific basis for rational fertilization and
      sustainable development in agriculture ecosystems. There were four treatments,
      including control (CK), inorganic fertilizer (NPK), inorganic fertilizer combined
      with manure (NPKM), and inorganic fertilizer combined with straw (NPKS). Illumina
      high-throughput sequencing and FUNGuild were performed to investigate the fungal
      community structure and functional group, respectively. Ascomycota,
      Basidiomycota, and Zygomycota were identified as the three dominant ones. The
      proportion of Ascomycota in NPKM and NPKS were significantly lower (49% and 47%,
      respectively) compared with CK (71%) and NPK (74%) treatments, with the main
      reduced orders of Hypocreales, Pleosporales and Eurotiales. While there was
      higher relative abundance of Basidiomycota in NPKM and NPKS (18% and 28%)
      compared to CK (14%) and NPK (10%), the orders with enhancement were Tremellales,
      Trechisporales, and Agaricales. The ratio of Basidiomycota was decreased with
      sole inorganic fertilizer. Moreover, the relative abundance of Zygomycota was
      increased after 33 years of fertilization, which was dominated by Mortierellales
      and Basidiobolales at order level. Diversity indices including Shannon, Simpson,
      Chao1 and ACE were all significantly declined in NPK compared with CK, NPKM and
      NPKS treatments, whereas Chao1 index and ACE index in NPKM and NPKS were higher
      than that in CK and NPK. Saprotroph was the main fungal functional group across
      all the four treatments (48%-57%). Higher proportion of symbiotroph fungi was
      identified in soils with NPKS and NPKM (17%) in comparison to CK and NPK. The
      main guilds with the increasing proportion were arbuscular mycorrhizal fungi and
      ectomycorrhizal fungi. However, significantly higher proportion of animal
      pathogen fungi were detected in NPK (10%) than other treatments. Redundancy
      analysis (RDA) showed that moisture, salinity and porosity in soil were more
      strongly related with fungal community composition and fungal functional
      composition than soil organic matter and total nitrogen. Our results suggest that
      sole application of inorganic fertilizer results in great changes in fungal
      community compositions and the hazard of over production of pathogen fungi,
      whereas combined organic-inorganic fertilization would be beneficial to maintain
      the healthy environment through increasing fungal diversity and the ratio of
      symbiotrophic fungi in yellow clayey paddy soil.

PMID- 30182614
TI  - [Sources and pollution characteristics of antibiotic resistance genes and
      conditional pathogenic bacteria in concentrated swine feeding operation.]
AB  - Air in concentrated animal feeding operations contains antibiotic resistance
      genes and airborne pathogens, with potential threat to human and animal health.
      In this study, air was sampled in the living area, outside, and inside of a
      fattening pig house in a pig farm for 24 and 48 hours. Feedstuffs, drinking water
      additives, and feces in the pig house were collected. Three kinds of antibiotic
      resistance genes (macrolide, beta-lactam, and tetracycline) and seven pathogenic
      microorganisms (Campylobacter, Clostridium perfringens, Enterococcus, Escherichia
      coli, Yersinia enterocolitica, Staphylococcus spp., and Streptococcus suis) were
      detected by polymerase chain reaction (PCR). Six genes with high detection rates
      were selected, with their concentrations being determined by real-time
      quantitative PCR (qPCR). Results showed that three macrolide and two tetracycline
      resistance genes were detected in all air samples. Enterococcus, Escherichia
      coli, Yersinia enterocolitica, and Staphylococcus spp. were detected in air
      samples and drinking water additive. The concentrations of most target genes were
      above 104 copies.m-3. The gene concentrations near the pig house were much higher
      than those in the living area. Main sources of antibiotic resistance genes and
      pathogens in the air were pig manure and drinking water additive. Sampling time
      of 24 h in the pig farm met the requirements for PCR detection. Sampling time of
      48 h had a higher sampling efficiency than that of 24 h in the living area of the
      pig farm, whereas sampling time of 24 h was more appropriate than that of 48 h in
      high bioaerosol concentration area such as the pig house.

PMID- 30182615
TI  - [Effects of sewage irrigation on growth of rice seedlings and soil environment
      with straw incorporation.]
AB  - The effects of sewage irrigation on the growth of rice seedlings and soil
      environment under wheat straw returning were examined with a pot experiment. Root
      morphology, root activity, tiller number, plant height, dry matter accumulation
      of rice seedling, soil ferrous ions content, organic acid content and enzyme
      activity were measured. The results showed that sewage irrigation significantly
      increased the number of tillers and root activity at 41 days after transplanting
      under no N fertilizer application. Under the same N input level, sewage
      irrigation combined with N fertilizer promoted the growth of rice seedlings and
      root, and increased the root length, root surface area, root volume, root
      activity, tiller number and dry matter accumulation. Sewage irrigation
      significantly reduced the contents of soil ferrous ions and organic acid, while
      significantly increased the activities of soil urease and catalase. These results
      indicated that the combination of sewage irrigation and N fertilizer could
      effectively reduce the negative effect of straw returning on rice seedling and
      thus enhance soil fertility and quality.

PMID- 30182618
TI  - [Spatial-temporal variation in population structure of Antarctic krill (Euphausia
      superba)in the Scotia Sea, Antarctic in 2016.]
AB  - The Scotia Sea occupies the highest density of Antarctic krill (Euphausia
      superba), which is the traditional fishing ground of krill fishery. However, the
      population structure of krill differed significantly inter-annually, seasonally
      and regionally. In order to understand the population dynamics of krill in this
      region, we analyzed the spatial-temporal variation on population structure of
      krill using samples collected randomly from fishery survey during January to
      September 2016. The results showed that sex ratio presented remarkably difference
      among different months. Females dominated in the population from January to May,
      but the opposite result occurred from June to September. During the survey period
      (January to September), juveniles only presented in the January popu-lation, and
      the percentage of adult females was over 40% and similar to that in February. The
      proportion of sub-adult females were over 50%, but the proportion of female
      adults were decreased gradually from March to May. The sub-adult males
      predominated in the population from June to August. The proportion of sub-adult
      females increased significantly but the number of male adults decreased in
      September. Sub-adult females occupied half of population in the Bransfield Strait
      from February to May. The proportion of spent females (25.6%) was higher than
      those of individuals with other sexual maturity stages and the gravid females
      occupied higher percentage of population off northeastern waters of the King
      George Island in January. From June to September, about half of the population
      was mature males, but the proportion of mature females was very low off
      northeastern waters of the South Georgia Island. Maturity stage composition
      indicated that peak spawning occurred in January and February and that spawning
      grounds occurred off northeastern waters of the King George Island and in the
      Bransfield Strait.

PMID- 30182617
TI  - [Effects of carbon supplementary modes on phosphorus bioaccumulation/phosphorus
      harvesting process in a tidal flow constructed wetland.]
AB  - We explored the effects of carbon supplementary modes on operational performance
      in a tidal flow constructed wetland (TFCW) utilizing phosphorus
      bioaccumulation/phosphorus harvesting (PB-PH) process. Three different carbon
      supplementary modes were adopted during the periodical phosphorus harvesting
      process. The results showed that the carbon supplementary mode significantly
      affected the performances of phosphorus bioaccumulation and phosphorus harvesting
      throughout the experiment. The optimization of carbon supplementary mode would
      facilitate the maintenance of abundance and activities of polyphosphate
      accumulating organisms (PAOs). Subsequently, the amounts of phosphorus release
      and PHB synthesis in PAOs, as well as the utilization rate of supplementary
      carbon, could be effectively enhanced during the phosphorus harvesting process.
      The efficient and stable phosphorus removal effects of the TFCW could be ensured
      during the phosphorus bioaccumulation process. When the PB-PH cycle length was 30
      d and using the continuous circulation carbon supplementary mode, the amount of
      phosphorus retained in the bed and the mean phosphorus harvesting efficiency of
      the TFCW were 26994.88 mg and 70.8%, respectively. Regarding a typical PB-PH
      cycle, the mean phosphorus removal efficiency of the TFCW could achieve (91.4+/
      2.1)% during the phosphorus bioaccumulation process. The amounts of phosphorus
      release and PHB synthesis in PAOs, and the utilization rate of supplementary
      carbon in the system could reach up to (1563.72+/-127.84) mg, (4.52+/-0.39) mmol
      C.g-1 VSS, and (97.3+/-1.6)%, respectively.

PMID- 30182616
TI  - [Concentrations and pollution assessment of mercury in farmland soil of Xinqiao
      Mining Area of Tongling, Anhui, China.]
AB  - To investigate the effects of mining activities on mercury (Hg) enrichment in
      farmland soil, soil samples were collected from four villages (Xinjian Village,
      Yehu Village, Xinhu Village and Hucheng Village) in the vicinity of Xinqiao
      Mining Area, Tongling. Hg concentration was measured by atomic fluorescence
      spectrophotometer. The geo-accumulation index was used to evaluate the Hg
      pollution level of the soils. The results showed that average concentration of
      total Hg in farmland soil was (0.137+/-0.078) mg.kg-1, which exceeded the
      background value of soil Hg in Tongling area. The average concentration of Hg in
      four villages followed the order of Xinjian Village (0.221 mg.kg-1)>Xinhu Village
      (0.118 mg.kg-1)>Yehu Village(0.115 mg.kg-1)>Hucheng Village (0.096 mg.kg-1).
      Moreover, the average Hg concentration of different forms in Xinjian Village
      followed the order of residue (0.036 mg.kg-1) > alkali soluble (0.031 mg.kg-1) >
      hydrogen peroxide soluble (0.022 mg.kg-1)> acid soluble (0.020 mg.kg-1)> water
      soluble (0.012 mg.kg-1). The distance from the mining area was the main factor
      affecting the distribution of soil Hg concentration in farmlands. The
      contaminated Xinqiao River, to some degree, had exa-cerbated soil Hg pollution.
      Soil organic matter affected the accumulation and transformation of total Hg and
      hydrogen peroxide Hg in the farmlands. The order of the geo-accumulation index
      followed as Xinjian Village(1.559) >Xinhu Village(0.654) >Yehu Village(0.616)
      >Hucheng Village(0.356). The pollution level of farmland soil in Xinjian Village
      belonged to middle level of Hg pollution,which deserved more attention.

PMID- 30182620
TI  - [Stock assessment methods on marine crustacean species: A review.]
AB  - Crustaceans, such as crab, lobster, prawn, and Antarctic krill, have formed a
      vast and commercially valuable fishery globally. Although the importance and
      scale of these crustacean fishe-ries are increasing, the suitable and effective
      methods for stock assessment and management of crustacean fisheries are urgent to
      be improved compared to other fisheries. We reviewed and evaluated four kinds of
      stock assessment methods for assessing crustacean fishery, including the surplus
      production model, delay-difference model, the depletion model, and size
      structured model. We described the application of those models in stock
      assessment of crustacean fishery, and briefly summarized the assumptions and data
      needed in these models. We further compared the advantages and disadvantages of
      those models. In addition, the assumptions of the models, the estimation method
      of the parameters, and the general solution of uncertainty were analyzed.
      Finally, the future direction and prospect of crustacean stock assessment were
      discussed.

PMID- 30182619
TI  - [Construction technology of amphibian habitat and the evaluation of its
      effectiveness.]
AB  - Drastic decline and extinction of amphibian species occurred around the world.
      Human-induced habitat loss and degradation are major threats to amphibians.
      Repairing or rebuilding amphibian habitat is an important way for amphibian
      restoration. During the process of urbanization, the construction of appropriate
      habitats is the key measure for amphibian conservation. In this study,
      construction technique and assessment of the reform amphibian habitat was carried
      out. To match the habitat requirements of five common amphibian species in
      Shanghai, Luhui seedling base in Pujiang Town (Minhang District, Shanghai, China)
      was selected as an experimental site from May 2014 to September 2016. We used
      ecological engineering measures that could provide amphibian habitat, such as
      changing topographic, adjusting water systems, vegetation restoration, and so on.
      To explore how these new technologies benefited amphibians' biodiversity, five
      sampling lines (100 m * 5 m) were selected and amphibians were monitored during
      the breeding period (May-June) and non-breeding period (August-September), once
      in each period in 2014 and 2016. A total of four species were recorded with a
      density of (164.0+/-63.7) ind.hm-2 in the breeding period in 2014, and four
      species with a density of (160.0+/-29.7) ind.hm-2 in the non-breeding period in
      2014, whereas five species with a density of (560.0+/-159.3) ind.hm-2 in the
      breeding period in 2016, and five species with a density of (628.0+/-186.2)
      ind.hm-2 in the non-breeding period in 2016. Our results suggested that this
      technology could significantly increase amphibians' biodiversity in the degraded
      amphibian habitat, which might be applied in other similar habitats in China.

PMID- 30182622
TI  - [Primary health care for people with an intellectual disability; room for
      improvement].
AB  - As people with an intellectual disability (ID) have more health needs than
      others, it is not surprising that they tend to request more out-of-hours GP care
      compared with the general population. Their requests, however, are more often
      classified at the lowest level of urgency. This raises questions, especially in
      times of over-stretched GP cooperatives and a general quest for efficiency. This
      commentary reflects upon current developments in care for people with ID, such as
      de-institutionalization and decreasing numbers of nursing staff in the
      Netherlands. It also stresses the importance of optimal health-information
      exchange between carers and the GP during office hours. The Netherlands has one
      of the best primary care systems in the world. The availability of highly
      qualified GPs with the support of specialized physicians for people with ID, if
      required, offers promising preconditions for accessible, high quality primary
      care for people with ID; however, this must be accompanied by organizational
      improvements by ID-care providers in the preparation and selection of requests
      before contacting out-of-hours GP cooperatives.

PMID- 30182621
TI  - [Construction of healthy wetland ecosphere in estuarine delta: Theory and
      method.]
AB  - The health of wetland ecosphere in an estuarine delta is determined by many
      factors, such as continuity of natural processes, ecosystem connectivity, habitat
      heterogeneity, and food web diversity. The contradiction between ecological and
      environmental protection and regional development in the estuarine delta is
      becoming more and more prominent. A series of man-made and natural processes
      directly and indirectly resulted in habitat fragmentation of wetlands, which has
      direct and strong impacts on the ecosphere health and the habitat function of
      wetlands. In this paper, we provided a perspective on researches on the basic
      theory of healthy wetland ecosphere, landscape ecological network system,
      hydrologic network construction, key food webs, and habitat heterogeneity. At the
      regional and landscape scales, with the linkages between land use and ecosystem
      integrity as the main line, we clarified the influences of habitat fragmentation
      on wetland ecological functions, especially the effects of landscape integrity
      and river connectivity on wetland habitat. At the community and ecosystem scales,
      emphasis should be given on the relationship between food web and ecosystem
      stability, especially the supporting role of food web diversity and habitat
      heterogeneity on the construction of wetland biosphere. Further efforts should
      focuse on the wetland habitats construction based on landscape integrity,
      hydrologic connectivity, habitat heterogeneity and food web diversity. These
      efforts could help to develop and optimize the theory and method of constructing
      wetland ecosphere and enhancing its ecological function, and promote the sound
      development of regional ecological environment and resource utilization in
      estuarine deltas.

PMID- 30182623
TI  - [Abdominal pain in a pregnant patient who had gastric reduction surgery: risks
      associated with a history of bariatric surgery].
AB  - Pregnant women who previously had bariatric surgery may develop acute abdominal
      pain during pregnancy that may be related to previous operations. Two patients, a
      38-year-old twin-primigravida who had a gestation period of 24+6 weeks and a 26
      year-old woman who had a gestation period of 24 weeks, both of whom had
      laparoscopic gastric bypass (RYGB) surgery 2 and 3 years previously, developed
      abdominal pain. The patients were not ill, but had diffuse abdominal pain in
      combination with normal blood tests and imaging. Patient B had undergone
      laparoscopy at another centre after 5 weeks of gestation for internal herniation.
      After referral to our multidisciplinary Bariatric-Obstetric-Neonatal (MD-BON)
      team, diagnostic laparoscopy was advised as internal herniation was deemed
      possible. In both patients, internal herniation was indeed found in Petersen's
      space and jejunal mesenteric defect, which was closed using laparoscopic surgery.
      Both women delivered healthy offspring afterwards. The presence of a MD-BON team
      allows for an increased awareness of potential long-term complications associated
      with earlier bariatric surgery in pregnancy.

PMID- 30182624
TI  - [Behavioural changes as a symptom: diagnosing behavioural variant frontotemporal
      dementia].
AB  - Behavioural variant frontotemporal dementia (bvFTD) is a neurodegenerative
      disease, the symptoms of which are changes in character, behavioural changes and
      socio-cognitive changes occurring predominantly at an age between 40 and 70
      years. Frontotemporal atrophy is apparent on diagnostic imaging in 70% of
      patients with bvFTD; a diagnostic dilemma arises if this is not clearly obvious.
      Validated questionnaires for stereotypical behaviour, depressive symptoms and
      apathy, and neuropsychological examination can be very helpful in differentiating
      between bvFTD and psychiatric and other neurological conditions. A brain MRI is
      always indicated in patients displaying behavioural changes; frontal or temporal
      atrophy on brain MRI provide sufficient support for the diagnosis 'probable
      bvFTD'. When in doubt, a supplementary 18F-FDG-PET scan can be performed, but
      hypometabolism on an 18F-FDG-PET scan can give a false-positive result. If bvFTD
      is suspected, a multidisciplinary approach, clinical follow-up for 2 years and
      referral to an FTD centre of excellence are recommended. Conflict of interest and
      financial support: none declared.

PMID- 30182625
TI  - [People with intellectual disabilities and GP cooperatives; more contact moments,
      less urgent].
AB  - OBJECTIVE: To compare use of the GP cooperative and the level of urgency among
      people with intellectual disabilities (ID) who live in sheltered accommodation
      with that of the general population. DESIGN: Cross-sectional study. METHOD: We
      investigated all healthcare-contact moments in 2014 among 432,582 people living
      in the servicearea covered by two GP cooperatives in one region of the
      Netherlands (Boxmeer, Nijmegen). In this region a total of 1,448 people with ID
      living in sheltered accommodation were identified on the basis of address
      details. We compared the type and frequency of contact and level of urgency
      between this group of people and the general population. RESULTS: Among people
      with ID living in sheltered accommodation, 30.9% (448/1,448) requested care from
      the GP cooperatives, compared with 18.4% (79,206/431,134) of the general
      population (relative risk [RR]: 1.7; 95% confidence interval [CI]: 1.6-1.8). The
      type and frequency of contact and level of urgency also differed between the two
      groups. Healthcare-contact moments among people with ID were more often conducted
      by telephone (RR: 2.7; 95% CI: 2.7-3.0) and were generally less urgent than in
      the general population. CONCLUSION: People with ID who live in sheltered
      accommodation make more use of the GP cooperative and more often have low-urgent
      telephone contacts in comparison with the general population. More insight is
      needed into the nature of healthcare-contact moments in order to improve the
      quality and accessibility of care from GP cooperatives for this vulnerable group.

PMID- 30182626
TI  - [Severe hypomagnesaemia due to proton pump inhibitor use].
AB  - BACKGROUND: Proton pump inhibitors (PPIs) are among the most widely used drugs
      around the globe. A growing body of literature, however, has reported numerous
      side effects, such as hypomagnesemia. Symptoms associated with hypomagnesaemia
      range from nausea, tetany and cardiac arrhythmias. Treatment of PPI-induced
      hypomagnesaemia involves discontinuation of the PPI and magnesium supplementation
      if needed. CASE DESCRIPTION: A 72-year-old female was admitted to the ICU with
      omeprazole-induced severe hypomagnesaemia twice during a one-year timespan,
      clinically manifested by tetany and respiratory failure due to acute
      decompensated heart failure following new onset atrial fibrillation. After
      discontinuation of the PPI and intravenous magnesium supplementation she
      recovered fully. CONCLUSION: Hypomagnesaemia is a potentially serious adverse
      effect of PPIs. Serum magnesium levels should be monitored in chronic PPI-users
      with any neuromuscular, cardiovascular or non-specific symptoms, especially in
      the presence of known risk factors (alcohol use, malnutrition, malabsorption,
      hypertension and concomitant use of diuretics).

PMID- 30182627
TI  - [Infection or metastases? The amoebic abscess].
AB  - BACKGROUND: Cases of Entamoeba histolytica infections in the Netherlands are
      usually imported diseases. The most common extra-intestinal manifestation of E.
      histolytica is the amoebic abscess. Patients can present with a clinical picture
      of colitis with pain in the upper right abdomen, accompanied by fever in cases of
      liver abscess. Diagnostics focus mainly on the detection of E. histolytica with
      PCR or ELISA. Infections are treated with metronidazole, with clioquinol as
      follow-up treatment. CASE DESCRIPTION: A 61-year-old, previously healthy man was
      admitted to hospital with pain in the upper right abdomen and fever. He had no
      history of travel in the tropics or sub-tropics. CT imaging revealed liver
      abscesses or liver metastases. Cultures of abscess fluid were negative. After
      extensive diagnostics the patient was shown to have an amoebic abscess for which
      he was successfully treated. CONCLUSION: If the bacterial cultures of liver
      abscess fluid continue to be negative the possibility of an amoebic abscess
      should be considered, even with a negative history of travel to the tropics or
      subtropics.

PMID- 30182628
TI  - [Within the limits of the law? Compulsory isolation and compulsory treatment for
      tuberculosis].
AB  - We discuss two patients with infectious tuberculosis who underwent compulsory
      isolation and treatment without their consent. We describe the threat to the
      patient's rights, i.e. the right of freedom, the right of autonomy and the right
      of protection of the integrity of the body. We describe the application of the
      relevant laws and of the differing safeguards, and discuss the unlimited length
      of the Dutch Public Health Act orders. We refer to a Dutch statement and the WHO
      ethics guidelines on the implementation of their End TB Strategy. Forced
      isolation may be the last resort to protect society from patients with infectious
      diseases who do not comply with isolation measures, but compulsory treatment for
      tuberculosis patients is considered unacceptable. We suggest an amendment of the
      Dutch Public Health Act to enable better protection of the rights of tuberculosis
      patients.

PMID- 30182629
TI  - [Identification and interpretation of abnormal walking patterns: a symptom-based
      approach for walking problems].
AB  - Identification and interpretation of abnormal walking patterns is important, for
      the diagnosis as well as the treatment of the underlying condition. Since walking
      pattern changes can often be clinically observed at an early stage, their
      identification can help with timely diagnosis. Clinical training makes use of
      comprehensive descriptions of walking abnormalities that list all possible
      characteristics of a classic syndrome. However, patients rarely present at the
      office with all clinical symptoms of a specific disease, certainly not in the
      earliest stages. Especially in the beginning, patients often display only one or
      at best a few abnormal walking characteristics. None of these individual
      characteristics is specific for a certain disease, but may instead be seen in
      combination with several different disorders. For this reason, we have developed
      a practical diagnostic approach which allows making a differential diagnosis for
      each abnormal walking characteristic. Focused history taking and physical
      examination can then be used to make an accurate diagnose or to refer the patient
      for further diagnostics.

PMID- 30182630
TI  - [Acute headache and neck pain caused by crowned dens syndrome].
AB  - BACKGROUND: Crowned dens syndrome (CDS) is a rare cause of acute headache and
      neck pain, which is accompanied by fever and a stiff neck. It is caused by
      calcium deposits (pseudogout) around the dens axis (C2). CASE DESCRIPTION: A 61
      year-old woman, with a history of migraine and of breast cancer 8 years
      previously, was referred to the accident and emergency department of our hospital
      with acute headache and neck pain. She was treated in the department with
      prednisone, on suspicion of giant-cell arteritis. However, an 18F-FDG-PET-CT
      showed inflammation and calcification around the dens, consistent with CDS. The
      patient's condition improved rapidly after treatment with prednisone. CONCLUSION:
      CDS should be considered in the differential diagnosis of acute headache and neck
      pain. Familiarity with the disease course can prevent unnecessary diagnostic
      tests and treatment. The syndrome can be easily diagnosed with a CT scan, but an
      18F-FDG-PET-CT can also be used to reveal inflammatory activity around the dens.

PMID- 30182631
TI  - [A man with a black oesophagus].
AB  - An 85-year-old man came to the emergency room because of vomiting a black fluid
      and melaena. He was hypotensive and had severe anaemia. We suspected an upper
      digestive tract bleeding and an gastroscopy was performed, which showed necrosis
      of the entire oesophagus. Within 24 hours of admission the patient died of
      hypovolemic shock.

PMID- 30182632
TI  - [Migrants' motives and expectations for contacting out-of-hours primary care].
AB  - BACKGROUND: Migrants relatively often use out-of-hours primary care. The
      objective of this study is to examine the motives and expectations of migrants
      for contacting out-of-hours primary care. METHODS: We used data from a survey
      study of 11,483 patients who contacted a General Practitioner (GP) cooperative in
      the Netherlands between 2009 and 2014 (response rate 45.6%). Logistic regression
      analysis was used to test differences in motives and expectations between non
      western and western migrants and native Dutch patients. RESULTS: The most
      frequently mentioned motives and expectation of migrants to contact out-of-hours
      primary care were similar to Dutch patients. The main motives for respectively
      non-western and western migrants were an urgent need for a GP (54.9%/52.4%),
      worry (49.3%/43.0%), and a need for medical information (21.3%/26.2%). Compared
      to natives, non-western migrants more often perceived an urgent need for a GP (OR
      1.65), less often needed information (OR 0.59), and like western migrants, more
      often experienced problems contacting their own GP during office hours (OR
      1.71(non-western/1.38(western)). Most non-western and western migrants expected
      to see a doctor (46.2%/46.6%) or get advice (39.6%/41.5%). Non-western migrants
      expected more often to get physical examinations (OR 1.53), and prescriptions (OR
      1.37). CONCLUSION: The main motives and expectations of migrants are similar to
      native Dutch patients, yet non-western migrants more often want action from the
      GP (e.g. examinations or prescriptions). At the same time, migrants experience
      problems accessing their own GP. We recommend education about the purpose of a GP
      cooperative, and examination and improvement of accessibility of daytime primary
      care.

PMID- 30182633
TI  - [Sexuality and intercultural communication; stories from a general practice].
AB  - Differences in ethnic background, culture, religion and language can impede
      communication between physicians and patients about sexuality. At the same time,
      most people, regardless of age, gender and cultural background, find sexuality an
      essential part of their lives. Sexual problems have a negative effect on
      perceived health. Many doctors think that non-Western migrants do not want to
      talk about sexuality and therefore - wrongly - do not mention this subject. With
      stories from daily practice, I want to show you that modesty, interest, respect,
      safety and appropriate information are the starting point for professional
      communication about sexuality. This is also the case for patients with non
      Western ethnic, cultural and religious backgrounds.

PMID- 30182634
TI  - [An enlarged thymus associated with Graves' disease].
AB  - BACKGROUND: Thyrotoxicosis and orbitopathy are the best-known expressions of
      Graves' disease. There are also rarer and less-known phenomena, such as thymic
      hyperplasia. Identification of these is important in order to avoid potentially
      unnecessary invasive interventions. CASE DESCRIPTION: In the case of two young
      women with lung embolisms, CT pulmonary angiography also revealed an enlarged
      thymus. This turned out to be caused by as of yet unknown Graves' disease. Since
      pathological examination of a thymus-biopsy sample was unable to rule out
      thymoma, thymectomy was performed on the first patient. Pathological examination
      of the entire thymus revealed hyperplasia. Additional FDG-PET/CT scan of the
      second patient revealed diffuse hyperactivity in the diffusely enlarged thymus.
      In this case, we opted for expectant treatment. A follow-up FDG-PET/CT scan 1
      year later, revealed a non-abnormal thymus. CONCLUSION: An enlarged thymus caused
      by thymic hyperplasia is a less well-known manifestation of Graves' disease. In
      case additional abnormalities develop in patients with Graves' disease, it is
      important to consider that these might be related to the disease before
      diagnosing an additional new condition.

PMID- 30182635
TI  - [A man with abdominal pain and pollakisuria].
AB  - An 18-year-old male presented in the emergency department with abdominal pain
      since two days and complaints of pollakisuria. Laboratory results showed
      increased infection parameters and ultrasound revealed an abscess in the
      abdominal lower right quadrant. The patient underwent diagnostic laparoscopy. We
      found an infected cyst, most likely an infected urachal remnant considering its
      location and the histological findings in the resected tissue.

PMID- 30182636
TI  - [The fragile yellow jersey: bone health in cyclists].
AB  - Although cycling has positive health effects, including improvement of
      cardiovascular fitness, it does not have a favourable effect on bone health. In
      professional cyclists, the bone mineral density (BMD) will actually have
      decreased at the end of an intensive season. As a professional cyclist's career
      progresses, there will be a further decrease in BMD particularly in the hip and
      lumbar spine. The forward leaning position, the repetitive movement at low
      intensity, and the fact that body weight is carried by the bicycle all contribute
      to non-stimulation of bone formation. The cyclists' low body weight, which is
      desirable for climbers in particular, and possibly their dietary pattern may
      exacerbate this negative effect. To reduce the risk of fractures both during and
      after a cycling career, it is desirable that more attention is paid to
      strengthening of the bones. The effectiveness of training programmes to
      strengthen the bones should be investigated in carefully designed research
      studies.

PMID- 30182637
TI  - [Tuberculosis: from compulsory admission to compulsory treatment].
AB  - Tuberculosis is still considered to be a threat to public health in the
      Netherlands. The Dutch Public Health Act enables the mandatory isolation of
      contagious patients who are not willing to be treated. However, this act does not
      mean that patients can be treated against their will. Another act, the Dutch
      Medical Treatment Act, regulates the contract between doctor and patient.
      According to this act, only patients who are mentally incompetent can be treated
      against their will. We describe two patients with contagious tuberculosis who are
      mentally incompetent. This article explains the steps which, in accordance with
      both acts, must be followed before starting appropriate treatment.

PMID- 30182639
TI  - Propolis as an adjuvant to non-surgical periodontal treatment: a clinical study
      with salivary anti-oxidant capacity assessment.
AB  - BACKGROUND: Periodontal diseases are characteristic for the excessive release of
      oxidant free-radicals by the host. The aim of the present study was to evaluate
      the efficacy of an anti-oxidant-based formula containing propolis and herbs as an
      adjunctive therapy to standard non-surgical periodontal treatment (NSPT) when
      compared to the domiciliary use of chlorhexidine-based formulae. METHODS: Forty
      patients were enrolled in the present study and randomly allocated to either a
      control (NSPT plus chlorhexidine gel formula) group or a test (NSPT plus anti
      oxidant gel formula) group. Clinical parameters for the assessment of the
      periodontal status were evaluated at baseline, one month, and three months after
      NSPT, and the salivary antioxidant capacity as well. RESULTS: There were no
      significant clinical differences between the two groups (P>0.05). However,
      patients within the test group (propolis) achieved better results in terms of
      oxidative stress reduction (P<0.05). CONCLUSIONS: In the present study, propolis
      was comparable to chlorhexidine in the clinical management of gingivitis. Further
      studies are needed to investigate its potential as a redox modulator for the oral
      microbiome.

PMID- 30182638
TI  - [A woman with blue fingers].
AB  - A 57-year-old woman presented to the Emergency Department with fingertips that
      turned blue, cold, and numb in several days. She noted a swelling in the lower
      abdomen that was diagnosed as ovarian cancer. Her fingers were affected by
      hypercoagulability as a paraneoplastic syndrome.

PMID- 30182640
TI  - Knowledge of primary care professionals about fluoride topics.
AB  - BACKGROUND: Scientific evidence on the benefits of fluoride was responsible for
      an important change in dental practice. Individual and collective actions have
      been planned to impact the epidemiology of oral health. However, questions around
      this topic persist, making discussions and researches still necessary. In this
      regard, the aim of this study was to verify the fluoride-related knowledge of
      pediatricians (PP) and dentists (DS) working in primary care, comparing related
      aspects such as its multiple sources of intake and dental fluorosis. METHODS: A
      group of PP and DS answered as self-administered questionnaire related to
      fluoride knowledge. PP group presented a lower level of adherence (34%) in
      comparison to the DS group (70%). RESULTS: Fluoride-related topics were learnt at
      undergraduate courses by 95,95% of dentists and 38.46% of pediatricians. Ninety
      two per cent of DS and 78.57% of PP claimed to know the clinical aspects of
      dental fluorosis. Pediatricians tend to indicate the use of fluoridated
      dentifrices at any age but advise less about the right amount to be placed on the
      toothbrush in comparison to DS. CONCLUSIONS: Dentists and pediatricians presented
      limited fluoride-related knowledge. Continued education/training is encouraged
      and necessary at this level in order to deliver the benefits of fluoride use to
      populations.

PMID- 30182641
TI  - Resin cements effect on the final color of novel monolithic CAD/CAM restorations.
AB  - BACKGROUND: This study investigated the effect of resin cement shade on the final
      color of computer aided design/computer aided manufacture (CAD/CAM) restorations.
      METHODS: Thirty CAD/CAM block specimens were fabricated (14*12*1.5 mm) by cutting
      blocks (Vita Mark II [VM], Vita Enamic [VE], and Lava Ultimate [LU]). Forty
      cement specimens were prepared (14*12*0.2 mm) using resin cement (RelyX Ultimate
      Tr, A1, A3O, Bl). Color measurements of CAD/CAM specimens were made without
      (control) and with each /shade of resin cement (test) with a spectrophotometer.
      Color differences (DeltaE00) between the control and test groups were calculated
      and analyzed by 2-way ANOVA and subsequent pairwise testing. Comparisons were
      performed by using Tukey's multiple comparison tests (alpha=0.05). RESULTS: Both
      cement shade and interaction between cement shade CAD/CAM block type parameters
      were significant on color differences (P<0.05). A3O cement resulted in a
      clinically unacceptable color differences (DeltaE00>2.25) for each tested CAD/CAM
      blocks. DeltaE00 values of VM_A1 and VE_A1 groups were also higher than
      clinically unacceptable level (DeltaE00>2.25). DeltaE00 value of VE_Tr was lower
      than visually perceptible level (?E00<=1.30). There was no statistically
      significant difference found between the ?E00 values of CAD/CAM blocks in the
      same shade of cement groups (P>0.05). CONCLUSIONS: Tested CAD/CAM blocks were
      similarly affected by the cement shade and thus may have similar optical
      features.

PMID- 30182642
TI  - Sub-periosteal peri-implant augmented layer technique for horizontal bone
      augmentation at implant placement.
AB  - In the present study, a novel surgical technique, namely the sub-periosteal peri
      implant augmented layer (SPAL), to increase hard and soft tissue dimensions at
      the most coronal portion of an implant will be thoroughly described. The surgical
      buccal access at the time of implant placement first consisted of a split
      thickness flap to raise the most superficial mucosal layer, followed by the
      elevation of the periosteal layer which was detached from the buccal cortical
      bone plate (BCBP). A full-thickness flap was elevated on the oral aspect. A
      xenograft was used to fill the space between the periosteal layer and the BCBP,
      and the periosteal layer was sutured to the oral flap. The mucosal layer was
      coronally advanced and sutured to submerge both the graft and the implants. At
      implant uncovering at 4 months, an increase in the thickness (>2 mm) of the
      buccal peri-implant tissues was observed. A free gingival graft was used to
      enhance the dimensions of buccal keratinized mucosa. The SPAL technique may
      represent a surgical option for the horizontal augmentation of peri-implant
      tissue thickness.

PMID- 30182643
TI  - [Evidence Based Secondary Prevention of Ischemic Heart Disease: Evidence of
      Secondary Preventive Management for Cardiovascular Disease].

PMID- 30182644
TI  - [Evidence Based Secondary Prevention of Ischemic Heart Disease. Topics: I.
      Advances and Evidence of Pharmacotherapy: 1. Antihypertensive Drug].

PMID- 30182645
TI  - [Evidence Based Secondary Prevention of Ischemic Heart Disease. Topics:  I.
      Advances and Evidence of Pharmacotherapy: 2. Up to Date Lipid Lowering
      Treatment].

PMID- 30182646
TI  - [Evidence Based Secondary Prevention of Ischemic Heart Disease. Topics: I.
      Advances and Evidence of Pharmacotherapy: 3. Antidiabetic Agents].

PMID- 30182647
TI  - [Evidence Based Secondary Prevention of Ischemic Heart Disease. Topics: I.
      Advances and Evidence of Pharmacotherapy: 4. Omega-3 Polyunsaturated Fatty Acid
      Reduces the Risk of Cardiovascular Events in the Patients with Ischemic Heart
      Disease].

PMID- 30182648
TI  - Science, clinical trials and ethics.

PMID- 30182649
TI  - Epidemiology of severe traumatic brain injury.
AB  - About 5.48 million people are estimated to suffer from severe traumatic brain
      injury (TBI) each year (73 cases per 100,000 people). The WHO estimates that
      almost 90% of deaths due to injuries occur in low- and middle-income countries
      (LMICs), where the 85% of population live. Of these trauma-related deaths TBI is
      the main cause of one-third to one-half and represents the greatest cause of
      death and disability globally among all trauma-related injuries. The primary
      causes of TBI vary by age, socioeconomic factors, and geographic region, so any
      planned interventions must take in account this variability. The road traffic
      injuries (RTI) scenario is still strictly connected to the analysis of the global
      incidence of TBI, and to the reason why the LMICs experience nearly 3 times as
      many cases of TBI proportionally than high-income countries (HICs). The
      proportion of TBIs resulting from road traffic collisions was greatest in Africa
      and Southeast Asia (both 56%) and lowest in North America (25%). In HICs, falls
      and RTIs were reported most frequently as cause of TBI, but the traumas
      attributable to RTIs dropped from 39% in 2003 to 24% in 2012, while those
      attributable to falls increased from 43% to 54% respectively, with an increase
      TBI in the elderly (>65 years) due to falls. Differently from HICs, the
      population with the peak of TBI incidence is younger in LMICs, with an age
      between 28.8 and 33.1, as extensively reported. The burden of disease is
      significant; between 1,730,000 and 1,965,000 lives could be saved if global
      trauma care were improved in LMICs. Clinical practice recommendation should be
      developed and created in environments where the severe TBI mainly occurs. The
      applicability of high-income-country clinical research standards in LMICs is an
      important topic for future international research.

PMID- 30182650
TI  - Transient diabetes insipidus after severe subarachnoid hemorrhage: not always
      central.

PMID- 30182651
TI  - Transient spontaneous regression of brainstem glioblastoma.

PMID- 30182653
TI  - [Evidence Based Secondary Prevention of Ischemic Heart Disease. Topics: I.
      Advances and Evidence of Pharmacotherapy: 6. Anticoagulant Therapy].

PMID- 30182652
TI  - [Evidence Based Secondary Prevention of Ischemic Heart Disease. Topics: I.
      Advances and Evidence of Pharmacotherapy: 5. Current Topics of Antiplatelet
      Drug].

PMID- 30182654
TI  - ?

PMID- 30182655
TI  - [Evidence Based Secondary Prevention of Ischemic Heart Disease. Topics: II.
      Advances and Evidence of Non-Pharmacotherapy: 1. Exercise Rehabilitation].

PMID- 30182656
TI  - [Evidence Based Secondary Prevention of Ischemic Heart Disease. Topics: II.
      Advances and Evidence of Non-Pharmacotherapy: 2. ICD, CRT-D].

PMID- 30182657
TI  - [A Case of Dermatomyositis Presenting with Severe Subcutaneous Edema in the Head
      and Neck].

PMID- 30182658
TI  - [TAFRO Syndrome with Bilateral Adrenal Hemorrhage].

PMID- 30182659
TI  - [Myelodysplasia Induced by Copper Deficiency of Unknown Origin].

PMID- 30182661
TI  - [Sleep Disturbances in Neurodegenerative Diseases].

PMID- 30182660
TI  - [Case of Relapsing Polychondritis with Diffuse Panbronchiolitis].

PMID- 30182662
TI  - [Recent Progress in Primary Aldosteronism].

PMID- 30182663
TI  - [Report from the Kanto Chapter Seminar: Practice and Task in Community Health
      Care at the Urban Areas Leaded by Physicians].

PMID- 30182664
TI  - [Series: Diagnosis at a Glance].

PMID- 30182665
TI  - [The 44th Scientific Meeting: Perspectives of Internal Medicine: Virology for
      Physician ~Recent Advance in Viral Infection and Treatment~:  1. Preface].

PMID- 30182666
TI  - [The 44th Scientific Meeting: Perspectives of Internal Medicine: Virology for
      Physician ~Recent Advance in Viral Infection and Treatment~: 2. Important Newly
      Emerging Viral Infection: 1) Ebola Virus Disease: Insights from the Largest
      Outbreak in West Africa].

PMID- 30182667
TI  - [The 44th Scientific Meeting: Perspectives of Internal Medicine: Virology for
      Physician ~Recent Advance in Viral Infection and Treatment~: 2. Important Newly
      Emerging Viral Infection: 2) Middle East Respiratory Syndrome (MERS)].

PMID- 30182668
TI  - Sino-Nasal Status in Patients with Chronic Obstructive PulmonaryDisease.
AB  - Background. Chronic obstructive pulmonary disease (COPD) is a preventable and
      treatable disease with seriousimpact on quality of life (QoL). There are limited
      studies available supporting coexistence of sino-nasal involvementin
      COPD.Methods. A prospective study was conducted to evaluate sino-nasal status in
      patients with COPD (n=100) presentingto the Department of Respiratory Medicine,
      Mahatma Gandhi Medical College and Hospital, Jaipur from July 2011to October
      2012. COPD was diagnosed based on the Global initiative on Obstructive Lung
      Disease (GOLD) guidelines.Sino-nasal status was assessed by detailed history,
      radiograph of the para-nasal sinuses (PNS), nasal endoscopyand mucociliary
      clearance time.Results. Sino-nasal symptoms were present in 74 patients with
      COPD; nasal discharge (75.7%) being the mostcommon. Tobacco smokers with COPD had
      a higher occurrence of sino-nasal symptoms (76.8%). Radiograph ofpara-nasal
      sinuses showed that maxillary sinus was most commonly involved. Nasal endoscopy
      revealed dischargein 63.5% cases. Nasal mucociliary clearance time was delayed
      (>11 to >40 min) in 98% cases. Nasal mucociliaryclearance time was significantly
      delayed (>20 min) in COPD patients who were tobacco smokers as compared tonon
      smokers (53.7% versus 16.7%) and also related with increasing severity of
      COPD.Conclusions. Our observations suggest that sino-nasal involvement and
      delayed mucociliary clearance are commonin patients with COPD, especially in
      tobacco smokers. Assessment of upper airway involvement in all the patientswith
      COPD can help better therapeutic intervention and improvement in QoL.

PMID- 30182669
TI  - [The 44th Scientific Meeting: Perspectives of Internal Medicine: Virology for
      Physician ~Recent Advance in Viral Infection and Treatment~: 2. Important Newly
      Emerging Viral Infection: 3) Avian Influenza].

PMID- 30182670
TI  - [The 44th Scientific Meeting: Perspectives of Internal Medicine: Virology for
      Physician ~Recent Advance in Viral Infection and Treatment~: 3. Common Viral
      Infectious Diseases; Viral Hepatitis: 1) Hepatitis B].

PMID- 30182672
TI  - [The 44th Scientific Meeting: Perspectives of Internal Medicine: Virology for
      Physician ~Recent Advance in Viral Infection and Treatment~: 3. Common Viral
      Infectious Diseases; Viral Hepatitis: 2) Hepatitis C].

PMID- 30182671
TI  - Comparison of Effect of Levocetirizine or Montelukast Alone and inCombination on
      Symptoms of Allergic Rhinitis.
AB  - Objective. To determine the effect of levocetirizine, montelukast and the
      combination of both the drugs on symptomsof allergic rhinitis.Methods. Seventy
      five patients with allergic rhinitis were randomly studied prospectively for a
      period of two weeksdivided into three groups receiving either levocetrizine or
      montelukast or combination of both. The outcomes weremeasured by a visual
      analogue score for nasal and eye symptom during day-time and night-time.Results.
      All the three regimens were equally effective in improving the day-time symptoms,
      like sneezing andrhinorrhea. There was also no difference in the control of night
      time and eye symptoms among the regimens.Conclusions. Montelukast, levocetirizine
      and their combination is equally effective in controlling symptoms, ofallergic
      rhinitis. Thus, use of montelukast alone would be cost-effective and do avoid
      adverse effects of levocetirizine in combination therapy

PMID- 30182674
TI  - [The 44th Scientific Meeting: Perspectives of Internal Medicine: Virology for
      Physician ~Recent Advance in Viral Infection and Treatment~: 3. Common Viral
      Infectious Diseases; Viral Hepatitis: 3) Hepatitis A and E].

PMID- 30182673
TI  - Pulmonary Vasculitis: Indian Perspective.
AB  - Pulmonary vasculitis is an uncommon disease. Patients present with unexplained
      haemoptysis, pulmonary infiltratesand constitutional symptoms. Pulmonary
      vasculitis often goes undiagnosed due to lack of awareness and thedisease is
      often mis-diagnosed as tuberculosis in India. Delayed or missed diagnosis leads
      to disease progressionto a catastrophic event like diffuse alveolar haemorrhage
      which carries a high mortality. The outcome of appropriatelytreated cases, on the
      contrary, is good with excellent long-term survival. The present narrative review
      attemptsto provide an overview of pulmonary vasculitis as it is seen in India.

PMID- 30182675
TI  - [The 44th Scientific Meeting: Perspectives of Internal Medicine: Virology for
      Physician ~Recent Advance in Viral Infection and Treatment~: 4. Viral Disease
      Commonly Observed in Outpatient Clinic: 1) Severe Fever with Thrombocytopenia
      Syndrome in Japan and Issues to Be Addressed].

PMID- 30182676
TI  - [The 44th Scientific Meeting: Perspectives of Internal Medicine: Virology for
      Physician ~Recent Advance in Viral Infection and Treatment~: 4. Viral Disease
      Commonly Observed in Outpatient Clinic: 2) Mosquito-borne Infectious Diseases,
      Such as Dengue Fever, and Its Vector Mosquitoes].

PMID- 30182677
TI  - Solitary fibrous tumour of pleura masquerading as lung fissural mass.

PMID- 30182678
TI  - [The 44th Scientific Meeting: Perspectives of Internal Medicine: Virology for
      Physician ~Recent Advance in Viral Infection and Treatment~: 4. Viral Disease
      Commonly Observed in Outpatient Clinic: 3) Current Status and Future Prospective
      in Medical Care of HIV-1 Infection/AIDS].

PMID- 30182680
TI  - [The 44th Scientific Meeting: Perspectives of Internal Medicine: Virology for
      Physician ~Recent Advance in Viral Infection and Treatment~: 5. Conclusion].

PMID- 30182679
TI  - Occupational emphysema following long-term exposure to metal fumes during
      electroplating in a non-smoker.
AB  - Exposure to cigarette smoke is by far the most common causative factor for
      chronic obstructive pulmonary disease.Occupational exposure to fumes, chemicals,
      dusts and environmental pollution is also an important cause of chronicproductive
      cough. Emphysema developing as a consequence of an occupational exposure is
      extremely rare. We describethe rare occurrence of severe emphysema in a non
      smoker male who had worked for nearly three decades in nickelelectroplating
      industry.

PMID- 30182682
TI  - [Programs for Continuing Medical Education 2016: A Session: 1. Development of the
      Medication for Liver Diseases with the Focus on the Medicines for Viral
      Hepatitis].

PMID- 30182681
TI  - Is Empirical Anti-tuberculous Treatment Justified Even in the Second Decade of
      the 21st Century?
AB  - Tuberculosis (TB) is a highly prevalent disease in developing countries where
      there is poor sanitation, over-crowdingand malnutrition. It can affect various
      organ systems in our body including the central nervous system,
      respiratory,genito-urinary tract and bone, though respiratory involvement is by
      far the commonest. Though diagnostic modalitiesfor TB are well defined, empirical
      therapy without a confirmed diagnosis continues to be used in specific
      clinicalsituations. We report two cases with suspected TB who served empirical
      treatment.

PMID- 30182683
TI  - [Programs for Continuing Medical Education 2016: A Session: 2. IBD and Gut
      Microbiota].

PMID- 30182684
TI  - Management of Chylothorax After Coronary Artery Bypass Grafting: Two Case Reports
      and Review of Literature.
AB  - Chylothorax following coronary artery bypass graft (CABG) surgery is a very rare
      complication and its managementis debatable. Opinions vary from early aggressive
      management to prolonged conservative treatment. We describetwo cases of post
      operative chylothorax following CABG and its management with intravenous
      octreotide.

PMID- 30182685
TI  - [Programs for Continuing Medical Education 2016: A Session: 3. Diagnosis and
      Treatment of Thyroid Diseases].

PMID- 30182687
TI  - [Programs for Continuing Medical Education 2016: A Session: 4. Obesity Disease
      and Metabolic Syndrome: Clinical Progress and Future Outlook].

PMID- 30182686
TI  - Syringo-pleural shunt: a rare cause of recurrent pleural effusion.
AB  - case of a patient with reported spinal tuberculosis (TB) that developed
      syringomyelia, a rare sequelae of thedisease is presented in this report. He
      underwent syringo-pleural shunting for syringomyelia. After 15 years, thepatient
      presented with recurrent pleural effusion. Diagnostic thoracentesis revealed
      fluid of transudative nature.Pleural fluid was positive for beta-2 transferrin.
      Pleural biopsy was negative for any malignancy or TB. Computedtomography scan
      focusing on the shunt showed that it was undisplaced. Video-assisted
      thoracoscopic explorationshowed the distal tip of the shunt adherent to the lung
      parenchyma. The effusion resolved after the dislodgementof distal tip from lung
      parenchyma.

PMID- 30182688
TI  - [Programs for Continuing Medical Education 2016: A Session: 5. Management of Life
      Style-related Disease to Prevent Atherosclerosis].

PMID- 30182689
TI  - Airway-centered Interstitial Fibrosis: An Unusual Presentation.
AB  - Airway-centered interstitial fibrosis (ACIF) is described as one of the
      interstitial lung diseases (ILDs) with rarehistologic patterns. It is
      characterised by predominant airway involvement with centrilobular fibrosis,
      peribronchiolarmetaplasia and bronchiolocentric inflammatory changes. We report
      the case of a female who presented withpneumothorax and central diabetes
      insipidus, diagnosed as ACIF on lung biopsy.

PMID- 30182690
TI  - [Programs for Continuing Medical Education 2016: A Session: 6. Up-to-date
      Treatment and Prevention of Cardiogenic Stroke].

PMID- 30182691
TI  - [Programs for Continuing Medical Education 2016: A Session: 7. Crossover Points
      of Asthma and COPD].

PMID- 30182692
TI  - [Programs for Continuing Medical Education 2016: A Session: 8. Recent Strategy to
      Treat Patients with Rheumatoid Arthritis].

PMID- 30182693
TI  - [Programs for Continuing Medical Education 2016: A Session: 9. Clinical Diagnosis
      Based on Physical Examination].

PMID- 30182694
TI  - [Programs for Continuing Medical Education 2016: B Session: 1. The Latest
      Clinical Findings and Treatments for Heart Failure].

PMID- 30182695
TI  - [Programs for Continuing Medical Education 2016: B Session: 2. Anti-hypertensive
      Therapy Based on Pathophysiology].

PMID- 30182696
TI  - [Programs for Continuing Medical Education 2016: B Session: 3. The Linkage
      between Kidney and Other Organs as Heart, Vessel, Bone and Anemia].

PMID- 30182697
TI  - [Programs for Continuing Medical Education 2016: B Session: 4. Latest Knowledge
      of COPD Management].

PMID- 30182698
TI  - [Programs for Continuing Medical Education 2016: B Session: 5. New Development of
      the Lung Cancer Treatment].

PMID- 30182699
TI  - [Programs for Continuing Medical Education 2016: B Session: 6. Malignant Lymphoma
      progress in Diagnosis and Treatment].

PMID- 30182700
TI  - [Programs for Continuing Medical Education 2016: B Session: 7. Current Treatment
      for Leukemia].

PMID- 30182701
TI  - [Programs for Continuing Medical Education 2016: B Session: 8. MERS Coronavirus
      Infection as an Emerging Infectious Disease].

PMID- 30182702
TI  - [Programs for Continuing Medical Education 2016: B Session: 9. Impact of
      Sarcopenia and Frailty on Preventive Care for Older People].

PMID- 30182703
TI  - [A Case of Pneumomycosis with Paraplegia].

PMID- 30182704
TI  - [A Case of Drug-induced Hypersensitivity Syndrome due to Trichloroethylene].

PMID- 30182705
TI  - [Current Opinion Concerning Appraisal of Health Check-up and Screening].

PMID- 30182706
TI  - The Heroic and Noble Life of Morizo ISHIDATE Commemorating the 115 years since
      his birth and 20 years since his death.
AB  - Morizo Ishidate was born in the city of Aomori on January 24, 1901, the third son
      in his family. As the 16th Director General of the NIHS, he announced his
      decision to reform the organization and implemented this action in 1966. In
      September 1970, as the president of the Central Pharmaceutical Affairs Council,
      he decided to stop the use of all quinoform preparations. On May 21, 1973, he
      held a historic talk with Dr. Taro Takemi. After the meeting, the separation of
      dispensing and prescribing functions opened a new chapter in pharmaceutical
      history. Such a heroic and noble life may be due to his faith. In April 1922, he
      entered "Doushikai," a dormitory belonging to Tokyo Imperial University.
      Yoshinosuke Konishi was his best friend in the dormitory. They joined a bible
      class directed by an American missionary, Miss Laura J. Mauk'. In September 1947,
      at the age of 49, Yoshinosuke decided to devote the rest of his life to being an
      evangelist. After that time, Morizo supported him for 33 years. At the age of 70,
      Morizo confessed his belief of Jesus Christ's resurrection from the dead based
      upon following words in the bible, "Therefore, if anyone is in Christ, he is a
      new creation. The old has passed away; behold, the new has come," (2 CORINTHIANS
      5 : 17). On July 18, 1996, he passed away at the age of 95.

PMID- 30182707
TI  - [Cutting Edge in the Diagnosis and Treatment of Pancreatic Neuroendocrine
      Neoplasms].

PMID- 30182708
TI  - Pharmacology in a Cup of Coffee The Virtue of Coffee and Vitamins Learned from
      the History of Scurvy and Dropsy.
AB  - Scurvy, a vitamin C deficiency, was rampant during the age of discovery in
      Europe. In the mid-17th century, "Pasqua Rosee," the first coffee house in
      London, put an ad in the newspaper "Publick Adviser" clearly stating, "It
      (coffee) is excellent to prevent and cure dropsy, gout, and scurvy." A
      Netherlands trade merchant carried the information to Nagasaki, Japan, along with
      coffee beans harvested in the Netherlands' new territory, Java Island. A Japanese
      physician in Nagasaki, Dr. Kai Hirokawa, translated the information into Japanese
      in his new book, "Dutch Medicines," published in 1803. According to the ancient
      documents stored in Wakkanai City, Japan, the coffee beans were distributed to
      Tsugaru Clan soldiers who were guarding the northern coastline from 1855 to 1856.
      The purpose of the distribution was the prevention of scurvy and dropsy. As the
      result, none of the soldiers died from scurvy during the winter of 1855-1856.
      This paper discusses the pharmacological relationship between coffee
      micronutrients and vitamin deficiency syndrome.

PMID- 30182709
TI  - Point Discharge Optical Emission Spectrometer as a Gas Chromatography (GC)
      Detector for Speciation Analysis of Mercury in Human Hair.
AB  - Speciation analysis of mercury in hair facilitates accurate evaluation of mercury
      exposure to humans and insights into the intertransformation of different mercury
      species in the human body. However, conventional hyphenated techniques used for
      mercury speciation analysis usually require expensive instruments and a complex
      interface. In this work, a compact and miniaturized point discharge (PD) atomic
      emission spectrometer was utilized as a detector of gas chromatography for the
      speciation analysis of mercury. Mercury species extracted from hair were
      derivatized to their volatile species with NaBEt4 and subsequently
      preconcentrated by headspace solid-phase microextraction (HS-SPME) prior to their
      speciation analysis. Under the optimized conditions, limits of detection of 0.35
      MUg kg-1 (0.035 ng) and 1.0 MUg kg-1 (0.10 ng) were obtained for IHg and MeHg,
      respectively, with a relative standard deviation (RSD) of better than 3.5%.
      Because of the compact and miniature conformation, high excitation capability,
      low power consumption of PD-OES, and efficient preconcentration of mercury
      species by HS-SPME, the proposed system not only overcomes the shortcomings
      associated with the conventional hyphenated techniques but also provides several
      unique advantages, including significant simplification of experimental setup,
      reduction of dead volume, and improvement of sensitivity. The accuracy of this
      system was validated by speciation analysis of mercury in a Certified Reference
      Material (GBW09101b, human hair) and 10 human hair samples collected from
      different people in the population.

PMID- 30182710
TI  - Electrostatic Constituents of the Interaction of Cardiolipin with Site A of
      Cytochrome c.
AB  - Cytochrome c binds to cardiolipin (CL) on the inner mitochondrial membrane during
      the initial stages of apoptosis where it oxidizes CL, promoting its release into
      the cytoplasm where it initiates apoptosis. Previous work has identified
      interaction sites on cytochrome c involved in the cytochrome c-CL interaction.
      The contributions of the lysines attributed to site A, the anionic site, are
      studied here to elucidate the relative importance of each for electrostatic
      interaction of cytochrome c with CL at pH 8, conditions where site A is dominant.
      A set of single, double, and quadruple lysine to alanine variants of yeast iso-1
      cytochrome c, at sequence positions 72, 73, 86, and 87, show that all contribute
      to the site A-mediated interaction with CL. All variants experience two
      sequential structural rearrangements as the lipid to protein ratio (LPR)
      increases. At a low LPR near 10, all variants undergo a small heme-centered
      structural change detected by Soret circular dichroism. At higher LPRs ranging
      from 22 to 34, all variants partially unfold as detected by Trp59 emission. The
      robustness of the mechanism of interaction to sequential neutralization of the
      four lysines assigned to site A demonstrates that site A is more extensive than
      previously supposed. The nature of both structural rearrangements also depends on
      which lysines constitute site A. The peroxidase activity of cytochrome c in the
      early stages of apoptosis depends on the nature of structural rearrangement near
      the heme. Thus, the lysines that comprise site A may have evolved to optimize the
      peroxidase signaling switch.

PMID- 30182711
TI  - Comparison of Electrical and Photoelectrical Properties of ReS2 Field-Effect
      Transistors on Different Dielectric Substrates.
AB  - As one of the newly discovered transition-metal dichalcogenides (TMDs), rhenium
      disulfide (ReS2) has been investigated mostly because of its unique
      characteristics such as the direct band gap nature even in bulk form, which is
      not prominent in other TMDs (e.g., MoS2, WSe2, etc.). However, this material
      possesses a low mobility and an on/off ratio, which restrict its usage in high
      speed and fast switching applications. Low mobilities or on/off ratios can also
      be caused by substrate scattering as well as environmental effects. In this
      study, we used few-layer ReS2 (FL-ReS2) as a channel material to investigate the
      substrate-dependent mobility, current on/off ratio, Schottky barrier height
      (SBH), and trap density of states of different dielectric substrates. The
      hexagonal boron nitride (h-BN)/FL-ReS2/h-BN structure was observed to exhibit a
      high mobility of 45 cm2 V-1 s-1, current on/off ratio of about 107, the lowest
      SBH of about 12 mV at a zero back-gate voltage ( Vbg), and a low trap density of
      states of about 5 * 1013 cm-3. These quantities are reasonably superior compared
      to the FL-ReS2 devices on SiO2 substrates. We also observed a nearly 5-fold
      improvement in the photoresponsivity and external quantum efficiency values for
      the FL-ReS2 devices on h-BN substrates. We believe that the photonic
      characteristics of TMDs can be improved by using h-BN as the substrate and
      capping layer.

PMID- 30182712
TI  - Understanding of the Graphene Oxide/Metal-Organic Framework Interface at the
      Atomistic Scale.
AB  - An atomistic model of the metal-organic framework (MOF) ZIF-8/graphene oxide (GO)
      interface has been constructed using a combination of density functional theory
      calculations and force-field-based molecular dynamics simulations. Two
      microscopic models of GO were constructed integrating basal plane and both basal
      and edge plane functional groups, called GO-OH and GO-CO2H, respectively.
      Analysis of the MOF/GO site-to-site interactions, surface coverage, and GO
      conformation/stiffness and a full characterization of the interfacial region is
      provided with a special emphasis on the influence of the chemical composition of
      GO. It was evidenced that the structure of the GO/ZIF-8 composite at the
      interface is stabilized by a relatively homogeneous set of interactions between
      the hydrogen atoms of the -NH and -OH terminal functions of ZIF-8 and the oxygen
      atoms of the epoxy, hydroxyl, and carboxylic groups of GO, leading to an optimal
      coverage of the MOF surface by GO. Such a scenario implies a significant
      distortion of the first GO layer brought into contact with the MOF surface,
      leading to an interfacial region with a relatively small width. This
      computational exploration strongly suggests that a very good compatibility
      between these two components would lead, in turn, to the preparation of defect
      free ZIF-8/GO films. These predictions are correlated with an experimental effort
      that consists of successfully prepared homogeneous MOF/GO films that were further
      characterized by transmission electron microscopy and mechanical testing.

PMID- 30182713
TI  - Comet-like Heterodimers "Gold Nanoflower @Graphene Quantum Dots" Probe with FRET
      "Off" to DNA Circuit Signal "On" for Sensing and Imaging MicroRNA In Vitro and In
      Vivo.
AB  - Cardiovascular diseases have recently become the number one cause of death
      worldwide and the risk of getting cardiovascular diseases is doubled as the age
      increases. MicroRNA-34a (miRNA-34a) as an important potential sensor of aging and
      cellular senescence could be used in early diagnostics. Herein, a new
      ultrasensitive platform on the basis of the fluorescence resonance energy
      transfer (FRET) "off" to DNA circuit signal "on" principle was established,
      termed comet-like heterodimers gold nanoflower (AuNF) @ graphene quantum dots
      (GQDs) probe. We discussed that the distance of 4 nm between AuNF and GQDs would
      increase fluorescence quenching efficiency, and light up sensitivity after the
      probe combined with a target miRNA initiating DNA circuit strategy. The target
      miRNA-34a can be quantified down to 0.1 fM, which is about 2 orders of magnitude
      lower than the existing sensing protocols. Furthermore, we constructed the aging
      myocardial cell and animal model, and the nanoprobe presented low cytotoxicity
      and satisfied signal imaging in vitro and in vivo. Significantly, this platform
      herein is envisioned to provide a reliable guidance for early diagnosing
      cardiovascular diseases and proposing therapeutic protocols.

PMID- 30182714
TI  - Combining Porous Magnetic Ni@C Nanospheres and CaCO3 Microcapsule as Surface
      Enhanced Raman Spectroscopy Sensing Platform for Hypersensitive C-Reactive
      Protein Detection.
AB  - In this work, we have designed an efficient and rapid surface-enhanced Raman
      spectroscopy (SERS) immunosensor for a supersensitive analysis of hypersensitive
      C-reactive protein (hs-CRP) with a label-free method by combining porous magnetic
      Ni@C nanospheres to aggregate together for simplifying the experiment operation
      and CaCO3 microcapsule to encapsulate rhodamine B as the Raman signal. The final
      solution containing the signal molecule was dropped on the Ag nanoparticle
      substrate, and the signal could be enhanced by Ag particles. First, rhodamine B
      was encapsulated in the CaCO3 microcapsule when it precipitated to form
      microcubes. Subsequently, the porous CaCO3 microcapsule was assembled layer by
      layer with poly(ether imide) (PEI) and a second antibody to obtain rhodamine
      B@CaCO3@PEI@Ab2. Then, the functionalized magnetic Ni@C nanospheres were prepared
      to immobilize the primary antibody (Ab1). Finally, the immunosensor was
      fabricated by the sandwiched antibody-antigen interactions. Compared to the DNA
      hydrogel, the low-cost CaCO3 microcapsule would be rapidly dissolved by ethylene
      diamine tetraacetic acid, releasing rhodamine B to produce a strong Raman signal
      for a rapid and efficient detection of hs-CRP. With the hs-CRP concentration
      ranging from 0.1 pg mL-1 to 1 MUg mL-1, the SERS intensity of the platform has a
      linear relationship with the logarithm of hs-CRP concentration, and the detection
      limit was 0.01 pg mL-1. By this smart design, this work can give a direction for
      a rapid label-free SERS analysis.

PMID- 30182715
TI  - Wafer-Scale Ultrathin, Single-Crystal Si and GaAs Photocathodes for
      Photoelectrochemical Hydrogen Production.
AB  - Crystalline Si and III-V compound semiconductors with appropriate band edge
      positions for the reduction of water have been widely utilized in
      photoelectrochemical (PEC) cells for the hydrogen evolution reaction (HER).
      However, the high cost of manufacturing those PEC cell photoabsorbers makes it
      difficult to achieve cost-effective hydrogen production. To overcome this issue,
      a new approach to fabricate a photoabsorber with low cost yet high performance
      for the HER is highly necessary. Here, we present a controlled fracture method,
      the so-called spalling process, to fabricate a cost-effective thin semiconductor
      applicable to the PEC HER. Using this method, a wafer-scale thin Si, whose
      thickness can be controlled from a few micrometers to sub-50 MUm, was fabricated
      from a thick Si mother substrate without material loss. Pt nanoparticle-decorated
      16 MUm thick spalled Si with an np+ rear junction exhibited an HER onset
      potential of 332 mV (vs reversible hydrogen electrode (RHE)) and a photocurrent
      density of 20.1 mA cm-2 at 0 V (vs RHE), which are the best performances among
      previously reported planar-type thin Si-based photocathodes. Finally, we
      demonstrated that 20 MUm thick GaAs could also be successfully fabricated by the
      spalling process, while exhibiting a PEC HER performance comparable to 350 MUm
      thick bulk GaAs.

PMID- 30182716
TI  - Inverted Device Architecture for Enhanced Performance of Flexible Silicon Quantum
      Dot Light-Emitting Diode.
AB  - Here we report for the first time highly flexible quantum dot light-emitting
      diodes (QLEDs), in which a layer of red-emitting colloidal silicon quantum dots
      (SiQDs) works as the optically active component, by replacing a rigid glass
      substrate with a thin sheet of polyethylene terephthalate (PET). The enhanced
      optical performance for electroluminescence (EL) at room temperature in air is
      achieved by taking advantage of the inverted device structure. Our QLEDs do not
      exhibit parasitic EL emissions from the neighboring compositional layers or
      surface states of QDs over a wide range of driving voltages and do not exhibit a
      shift in the EL peak position as the operational voltage increases. Compared to
      the previous Si-QLEDs with a conventional device structure, our QLED has a longer
      device operational lifetime and a long-lived EQE value. The currently obtained
      brightness (~5000 cd/m2), the 3.1% external quantum efficiency (EQE), and a turn
      on voltage as low as 3.5 V are sufficiently high to encourage further
      developments of Si-QLEDs.

PMID- 30182717
TI  - Chelate-Free Synthesis of the U(II) Complex, [(C5H3(SiMe3)2)3U]1-, Using Li and
      Cs Reductants and Comparative Studies of La(II) and Ce(II) Analogs.
AB  - To expand the range of synthetic options for generating complexes of the actinide
      metals in the +2 oxidation state, reduction of Cp"3U (Cp" = C5H3(SiMe3)2) and the
      lanthanide analogs, Cp"3La and Cp"3Ce with lithium in the absence of crown ether
      and cryptand chelates was explored. In each case, crystallographically
      characterizable [Li(THF)4][Cp"3M] complexes were obtainable in yields of 70-75%
      for M = La and Ce and 45-50% for M = U, that is, chelating agents are not
      necessary to sequester the lithium countercation to form isolable crystalline
      M(II) products. Reductions using Cs were also explored and X-ray crystallography
      revealed the formation of an oligomeric structure, [Cp"U(MU-Cp")2Cs(THF)2] n,
      involving Cp" ligands that bridge "(Cp"UII)1+" moieties to "[Cp"2Cs(THF)2]1-"
      units.

PMID- 30182718
TI  - Ion Removal Performance, Structural/Compositional Dynamics, and Electrochemical
      Stability of Layered Manganese Oxide Electrodes in Hybrid Capacitive
      Deionization.
AB  - Hybrid capacitive deionization (HCDI) is a derivative of capacitive deionization
      (CDI) method for water desalination, in which one carbon electrode is replaced
      with a redox-active intercalation electrode, resulting in substantial
      improvements in ion removal capacity over traditional CDI. The search for high
      performing intercalation host compounds is ongoing. In this study, two-layered
      manganese oxides (LMOs), with sodium (Na-birnessite) and magnesium (Mg-buserite)
      ions stabilizing the interlayer region, were for the first time evaluated as HCDI
      electrodes for the removal of ions from NaCl and MgCl2 solutions to understand
      structural/compositional dynamics and electrochemical stability of LMO electrodes
      over extended cycling. Both materials demonstrated excellent initial ion removal
      performance with the highest capacities of 37.2 mg g-1 (637 MUmol g-1) exhibited
      by Mg-buserite in NaCl solution and 50.2 mg g-1 (527 MUmol g-1) exhibited by Na
      birnessite in MgCl2 solution. The performance decay observed over the course of
      200 ion adsorption/ion release cycles was attributed to two major phenomena:
      oxidation of carbon electrode and evolution of the structure/composition of LMO
      electrodes. The latter involves disorder in stacking of Mn-O layers and changes
      in the interlayer spacing/interlayer ions reflecting the composition of the
      solution being desalinated. This work highlights the importance of understanding
      the interactions between the HCDI electrodes and solutions containing different
      ions and the structural analysis of redox-active material in intercalation
      electrodes over the course of operation for gaining insight into the fundamental
      processes governing desalination performance and developing next-generation HCDI
      systems with long-term electrochemical stability.

PMID- 30182719
TI  - X-ray Linear Dichroism in Apatite.
AB  - The recent observation in parrotfish teeth of X-ray linear dichroism motivated an
      in-depth investigation into this spectroscopic effect in various apatite
      crystals, including geologic hydroxyapatite (Ca5(PO4)3OH), fluorapatite
      (Ca5(PO4)3F), and their biogenic counterparts in human bone, mouse enamel, and in
      parrotfish bone, dentin, and enameloid, the equivalent of dental enamel in
      certain fish. These data are important because they now enable visualization of
      the nano- to microscale structure of apatite crystals in teeth and bone.
      Polarization-dependent imaging contrast (PIC) maps of lamellar bone, obtained
      with a new method that minimizes space-charge and charging effects, show the
      expected rotating apatite crystal orientations. PIC maps of mouse enamel reveal a
      complex arrangement of hydroxyapatite crystals perpendicular to the dentin-enamel
      junction, with rods arranged in a decussation pattern in inner enamel and nearly
      parallel to one another in outer enamel. In both inner and outer enamel crystal c
      axes are not always aligned with the rod elongation direction.

PMID- 30182720
TI  - Ultralarge Single-Layer Porous Protein Nanosheet for Precise Nanosize Separation.
AB  - Highly permeable and precisely size-selective membranes are the subject of
      continuous pursuit for energy-efficient separation of fine chemicals. However,
      challenges remain in the fabrication of an ultrathin selective layer with
      homogeneous pores, in particular, with the pore sizes in the 1-10 nm range. We
      report the design of a free-standing porous nanosheet assembled with a single
      layer of proteins. Tobacco mosaic virus mutant (TMVm), a cylinder-shaped protein
      containing an inner pore of 4 nm in diameter, was cross-linked via a Cu2+
      catalyzed disulfide-bond-forming reaction along the 2D orientation. By such a
      design, ultralarge single-layer TMVm nanosheets extending over tens of
      micrometers in width and with well-defined nanopores were successfully developed.
      A ~40 nm thick ultrafiltration membrane laminated by the single-layer TMVm
      nanosheets through simple vacuum filtration accomplished the precise separation
      of ~4 nm sized substances. Meanwhile, the membrane exhibited water permeance up
      to ~7000 L m-2 h-1 bar-1, which is an order of magnitude improvement compared
      with traditional ultrafiltration membranes with a similar rejection profile.

PMID- 30182721
TI  - Metal-Free Dehydrogenative Diels-Alder Reactions of Prenyl Derivatives with
      Dienophiles via a Thermal Reversible Process.
AB  - An efficient dehydrogenative Diels-Alder reaction of prenyl derivatives with
      dienophiles has been developed. The reaction exhibits broad substrate scope and
      provides efficient access to cyclohexene derivatives with good to excellent
      yields. A reasonable mechanism involving a metal-free thermal reversible process
      is proposed.

PMID- 30182722
TI  - Integrating High-Resolution Material Flow Data into the Environmental Assessment
      of Waste Management System Scenarios: The Case of Plastic Packaging in Austria.
AB  - The environmental performance of the waste management system of plastic packaging
      in Austria was assessed using a combination of high-resolution material flows and
      input-dependent life cycle inventory data. These data were used to evaluate
      different configurations of the waste management system, reflecting the system
      structure as it was in 1994 in Austria and still is in some of the new EU member
      states, as well as a situation achieving the increased circular economy targets
      to be met by 2030. For the latter, two options, namely single-polymer recycling
      and mixed-polymer recycling, were investigated. The results showed that the
      status quo achieves net benefits for 15 out of 16 impact categories evaluated.
      Regarding the alternative scenarios, for most impact categories these benefits
      increased with increasing recycling rates, although for four impact categories
      the highest net benefit was achieved by the status quo. For many impact
      categories the marginal environmental benefit decreased at higher recycling
      rates, indicating that there is an environmentally optimal recycling rate below
      100%. The results also highlight the importance of high-quality single-polymer
      plastics recycling from an environmental perspective because utilizing mixed
      polymer recycling to achieve circular economy targets would result in lower
      environmental benefits than the status quo.

PMID- 30182723
TI  - Adopting RCA2: The Interrater Reliability of Safety Assessment Codes.
AB  - Safety assessment codes (SACs) are one method to evaluate adverse events and
      determine the need for a root cause analysis. Few facilities currently use SACs,
      and there is no literature examining their interrater reliability. Two
      independent raters assigned frequency, actual harm, and potential harm ratings to
      a sample of patient safety reports. An actual and potential SAC were determined.
      Percent agreement and Cohen's kappa were calculated. Substantial agreement
      existed for the actual SAC (kappa = 0.626, P < .001), fair agreement for the
      potential SAC (kappa = 0.266, P < .001), and low agreement for potential harm
      (kappa = 0.171, P = .002). Although there is subjectivity in all aspects of
      assigning SACs, the greatest is in potential severity. This presents a problem
      when using the potential SAC and is in agreement with previous literature showing
      significant subjectivity in determining potential harm. An operational framework
      is needed to strengthen reliability.

PMID- 30182724
TI  - Effects of the Number of Muscle-Nerve-Muscle Grafts on Rat Facial Nerve
      Functional Recovery.
AB  - INTRODUCTION: Facial nerve denervation can be devastating for patients. Primary
      neurorrhaphy and interposition (IP) nerve grafting are common reinnervation
      techniques. Muscle-nerve-muscle (MNM) grafting is a lesser known alternative.
      After previously demonstrating significant return of function using MNM grafting
      in a rat facial nerve model, the authors compare the use of multiple MNM nerve
      grafts with that of single MNM and IP nerve grafts. METHODS: Thirty-six male rats
      were randomized into 4 groups: (1) repair with IP grafts, (2) 1 MNM graft, (3) 3
      MNM grafts, and (4) control with no intervention. All groups had the lower
      zygomatic, buccal, and marginal mandibular branches of the right facial nerve
      removed. Return of movement and snout symmetry was measured over 16 weeks. Axonal
      regeneration and muscle atrophy were assessed and quantified. RESULTS: All
      intervention groups had significantly improved movement and snout symmetry
      compared with control. Rats in the IP group had significantly increased axon
      density compared with those in the MNM groups but with smaller axonal diameter
      than control rats. No difference in axon density or diameter was observed between
      MNM groups. Use of 3 MNM grafts and IP grafts resulted in preservation of similar
      muscle mass compared with the control and 1-MNM groups. CONCLUSION: MNM grafting
      may be an alternative when other reanimation techniques are not possible. LEVEL
      OF EVIDENCE: NA.

PMID- 30182725
TI  - Validation of direct method to quantify dexamethasone in human aqueous humor by
      LC-MS/MS.
AB  - AIM: Dexamethasone (Dex) has been used for the treatment of ocular diseases,
      presenting concentrations up to 150 ng/ml in the biological matrix. Drug sampling
      has been performed from aqueous humor (AH), which the volume varies from 50 to
      200 MUl, becoming a challenge for analytical analyses. RESULTS: We developed and
      validated a direct and sensitive method by LC-MS/MS for Dex measurement in human
      AH, using water as surrogate matrix to reduce the sample volume applied in some
      validation assays. With accuracies of 99.6% and precision within 15% in the range
      of 0.1-150 ng/ml, Dex had an 87-day stability. CONCLUSION: Our method is robust
      and sensitive enough to be applied in bioequivalence studies with human AH using
      only 20 MUl of biological sample.

PMID- 30182726
TI  - Proposed selection strategy of surrogate matrix to quantify endogenous substances
      by Japan Bioanalysis Forum DG2015-15.
AB  - It is important to select an appropriate surrogate matrix for preparing
      calibration standards and quality control samples while quantitatively assaying
      for endogenous substances, because a blank matrix that does not contain the
      endogenous substance cannot be derived from the species from which the target
      study samples are collected. This is because the assay results might be affected,
      depending on the characteristics of the analyte in the surrogate matrix. Our
      discussion group that participated in the Japan Bioanalysis Forum discussed the
      recommended selection strategies, focusing on large and small molecules in ligand
      binding assays and LC-MS, respectively. We established an efficient selection
      strategy for a surrogate matrix, with simple compositions as the first candidates
      stated in this article.

PMID- 30182727
TI  - Optimization and qualification of the single molecule array digital immunoassay
      for IL-12p70 in plasma of cancer patients.
AB  - AIM: Cytokine/chemokine levels can reflect the pharmacodynamics of checkpoint
      inhibitors. The single molecule array (Simoa) HD-1 is a sensitive next-generation
      immunoassay platform for quantification of low abundance proteins, with potential
      for cancer immunotherapy mechanism of action studies. RESULTS: The Simoa IL-12p70
      reagents, standard curve and test conditions were optimized for improved
      precision and linearity of dilution in plasma of cancer patients. The assay
      achieved a lower limit of quantification of 0.08 pg/ml, with 27/29 samples
      recording above lower limit of quantification, precision <=20% CV and accuracy
      within 80-120%. CONCLUSION: Simoa enabled quantification of IL-12p70 at sub-pg/ml
      levels in cancer patients and was superior to Simple PlexTM and Aushon(r) in
      overall performance. This study qualifies the user-modified IL-12p70 immunoassay
      to measure pharmacodynamic changes in plasma during cancer immunotherapy.

PMID- 30182730
TI  - The impact of HIV couple testing and counseling on social support among pregnant
      women and their partners in Lilongwe, Malawi: an observational study.
AB  - Couples HIV testing and counseling (couple counseling) promotes safer sexual
      behaviors, increases communication between couples, and decreases HIV
      transmission. However, the impact of couple counseling on social support,
      critical for persons living with HIV, has not been examined. Ninety couples with
      a recently tested HIV-positive pregnant woman (female-positive couples) and 47
      couples with a recently tested HIV-negative pregnant woman (female-negative
      couples) were enrolled in an observational study at an antenatal clinic in
      Malawi. Each couple member was assessed immediately before and one month after
      couple counseling for partner, family, and peer social support using the
      Multidimensional Scale of Perceived Social Support. Before couple counseling,
      social support was lower among women than men in both female-positive couples
      (beta = -10.00, p < .01) and female-negative couples (beta = -8.43, p  < .01).
      After couple counseling, social support increased for women in female-positive
      couples (beta = 4.01, p < .01) and female-negative couples (beta = 4.69, p < .01)
      but not for men in either type of couple. Couple counseling could be an effective
      strategy to increase social support for women, including those with recent HIV
      diagnoses.

PMID- 30182728
TI  - Postoperative Monitoring Following Adenotonsillectomy for Severe Obstructive
      Sleep Apnea.
AB  - INTRODUCTION: Patients undergoing adenotonsillectomy (T&A) for severe obstructive
      sleep apnea (OSA) are usually admitted for observation, and many surgeons use the
      intensive care unit (ICU) for observation due to the risk of postsurgical airway
      obstruction. Given the limited resources of the pediatric ICU (PICU), there is a
      push to better define the patients who require postoperative monitoring in the
      PICU for monitoring severe OSA. METHODS: Forty-five patients were evaluated.
      Patients who had cardiac or craniofacial comorbidities were excluded. Patients
      undergoing T&A for severe OSA were monitored in the postanesthesia care unit
      (PACU) postoperatively. If patients required supplemental oxygen or developed
      hypoxia while in the PACU within the 3-hour monitoring period, they were admitted
      to the PICU. RESULTS: Overall, 16 of 45 patients were admitted to the ICU for
      monitoring. Patients with an Apnea-Hypopnea Index (AHI) >50 or with an oxygen
      nadir <80% were significantly more likely to be admitted to the PICU. The mean
      AHI of patients admitted to the PICU was 40.5, and the mean oxygen nadir was
      69.9%. Patients younger than 2 years were significantly more likely to be
      admitted to the PICU. CONCLUSION: Based on the data presented here and academy
      recommendations, not all patients with severe OSA require ICU monitoring.

PMID- 30182731
TI  - Circular RNA hsa_circ_0072995 promotes breast cancer cell migration and invasion
      through sponge for miR-30c-2-3p.
AB  - AIM: To study the role of hsa_circ_0072995 in regulating the invasion and
      migration of breast cancer cells. MATERIALS & METHODS: Hsa_circ_0072995
      expression was confirmed by quantitative real-time PCR; evaluating the migration
      and invasion of breast cancer cells through transwell assay; predicating
      circRNA/microRNAs interaction using the miRanda and RNAhybrid software;
      identifying the relationship between hsa_circ_0072995 and miR-30c-2-3p by
      luciferase activity assay; detecting the location of hsa_circ_0072995 by
      Fluorescence in situ hybridization assay. RESULTS: Hsa_circ_0072995 was
      significantly upregulated in MDA-MB-231 cells compared with MCF-7 cells.
      Hsa_circ_0072995 regulated the invasion and migration of breast cancer cells.
      Hsa_circ_0072995 existed in the nucleus and cytoplasm, and the proportion of the
      two was roughly equal. Hsa_circ_0072995 bound to miR-30c-2-3p. Overexpression of
      miR-30c-2-3p inhibited breast cancer cells migration and invasion. Low expression
      of miR-30c-2-3p was correlated with poor overall survival by The Cancer Genome
      Atlas database. CONCLUSION: Hsa_circ_0072995 may be a novel biomarker for breast
      cancer, and may function in metastasis of breast cancer.

PMID- 30182732
TI  - Methylomic changes in response to micronutrient supplementation and MTHFR
      genotype.
AB  - : Exposure times and dosage required for dietary components to modify DNA
      methylation patterns are largely unknown. AIM: This exploratory research
      represents the first genome-wide analysis of DNA methylation changes during a
      randomized-controlled-trial (RCT) for dietary supplementation with broad spectrum
      vitamins, minerals and amino acids in humans. METHODS: Genome-wide changes in
      methylation from paired, peripheral blood samples were assessed using the
      Infinium Methylation EPIC 850 K array. RESULTS: Methylation increased at 84% of
      the most significant differentially methylated CpGs; however, none showed
      significance after adjustment for genome-wide testing. CONCLUSION: Micronutrient
      supplementation is unlikely to have a substantial biological effect on DNA
      methylation over 10 weeks; however, the trend toward hypermethylation that we
      observed is likely to become more marked with longer exposure periods.

PMID- 30182733
TI  - Screening key long non-coding RNAs in early-stage colon adenocarcinoma by RNA
      sequencing.
AB  - AIM: We aim to identify the key long noncoding RNAs (lncRNAs) in early-stage
      colon adenocarcinoma (COAD). PATIENTS & METHODS: Compared with colonic
      intraepithelial neoplasia, differentially expressed lncRNAs (DElncRNAs) in early
      stage COAD were obtained by RNA-sequencing. Our previous work has obtained the
      differentially expressed mRNAs and miRNAs (DEmRNAs and DEmiRNAs) in early-stage
      COAD. DEmiRNA-DElncRNA-DEmRNA interaction analysis and functional annotation were
      performed. Validation of expression and receiver-operating characteristic
      analyses were performed based on The Cancer Genome Atlas. RESULTS: Seventy-nine
      significantly DElncRNAs in early-stage COAD were obtained. MiR-153-3p-TUG1
      DAPK1/ARNT2/KLK3/PLD1/SMAD2 and miR-153-3p-SNHG17-COL11A1/IGFBP3/KLF6
      interactions were associated with early-stage COAD. Five DElncRNAs (ELFN1-AS1,
      LINC01234, SNHG17, UCA1 and LOC101929549) involved in early-stage COAD with
      potential diagnostic value. CONCLUSION: LncRNAs involve in early-stage COAD by
      interaction with COAD-regulated genes and miRNAs.

PMID- 30182734
TI  - Diagnostic and prognostic biomarkers of common urological cancers based on
      aberrant DNA methylation.
AB  - AIM: We intended to construct DNA methylation-based models for the diagnosis and
      prognosis of three common urological cancers including prostate adenocarcinoma,
      renal clear cell carcinoma and bladder urothelial carcinoma. MATERIALS & METHODS:
      Total 450K methylation array data from the cancer genome atlas and gene
      expression omnibus datasets were downloaded. Moderated t-statistics and least
      absolute shrinkage and selection operator method were used to build diagnosis and
      prognosis models. RESULTS: Our diagnostic panels including 128 CpG sites had high
      sensitivity and accuracy in distinguishing samples and could identify lymphatic
      metastases in prostate adenocarcinoma patients. The prognostic models with 19 CpG
      sites for renal clear cell carcinoma and 21 CpG sites for bladder urothelial
      carcinoma were able to distinguish high- and low-risk patients and improve the
      predictive ability of the tumor node metastasis staging system. CONCLUSION: DNA
      methylation may afford reliable biomarkers in the diagnosis and prognosis of
      common urological cancers.

PMID- 30182735
TI  - Development of an HPLC-MS/MS method to determine janagliflozin in human plasma
      and urine: application in clinical study.
AB  - AIM:  Janagliflozin is a novel, orally selective sodium-glucose co-transporter-2
      (SGLT2) inhibitor, which showed good efficacy and safety in preclinical study.
      The objective of this study is to develop and validate the HPLC-MS/MS method to
      determine janagliflozin in both of human urine and plasma. METHODS: 
      Janagliflozin was separated on Waters Xbridge Phenyl C18 column and detected on
      API 4000 tandem mass spectrometer with ESI source in negative mode. RESULTS: This
      method provided good linearity in the range of 5-5000 ng/ml and 5-1000 ng/ml in
      plasma and urine. The matrix effect and extraction recoveries across three
      concentration levels were consistent. CONCLUSION: This validated method is
      reliable and has been successfully applied to a first-in-human trial of
      janagliflozin in Chinese subjects.

PMID- 30182736
TI  - Digital Diabetes Data and Artificial Intelligence: A Time for Humility Not
      Hubris.
AB  - In the future artificial intelligence (AI) will have the potential to improve
      outcomes diabetes care. With the creation of new sensors for physiological
      monitoring sensors and the introduction of smart insulin pens, novel data
      relationships based on personal phenotypic and genotypic information will lead to
      selections of tailored, effective therapies that will transform health care.
      However, decision-making processes based exclusively on quantitative metrics that
      ignore qualitative factors could create a quantitative fallacy. Difficult to
      quantify inputs into AI-based therapeutic decision-making processes include
      empathy, compassion, experience, and unconscious bias. Failure to consider these
      "softer" variables could lead to important errors. In other words, that which is
      not quantified about human health and behavior is still part of the calculus for
      determining therapeutic interventions.

PMID- 30182737
TI  - Chronic lymphocytic leukemia patients with heterogeneously or fully methylated
      LPL promotor display longer time to treatment.
AB  - AIM: We investigated whether DNA methylation regulates expression of LPL and PI3K
      complex genes in chronic lymphocytic leukemia (CLL) and evaluated the prognostic
      significance of LPL promoter methylation in CLL patients. Patients & methods:
      Methylation of LPL promoter was assessed in 112 patients using methylation
      sensitive high-resolution melting (MS-HRM). RESULTS: Patients with a fully or
      heterogeneously methylated LPL promoter had significantly longer median time to
      treatment (p < 0.001) and 75% lower (hazard ratio: 0.25; 95% CI: 0.15-0.42; p <
      0.001) risk of requirement for treatment as opposed to patients with
      nonmethylated promoter. Multivariate modeling confirmed independent prognostic
      value of these findings. CONCLUSION: Chronic lymphocytic leukemia patients with a
      fully or heterogeneously methylated LPL gene promoter display indolent disease
      course and acquisition of heterogeneous methylation of LPL promoter is
      insufficient to induce gene expression.

PMID- 30182738
TI  - 'Thunder bolts and lightning': survival and neurorehabilitation following out of
      hospital cardiac arrest secondary to lightning strike.
AB  - BACKGROUND: There is a limited evidence base to inform patient management
      following lightning-induced injuries. CASE REPORT: A 36-year-old right-handed
      Caucasian male struck by lightning while outdoors suffered an out-of-hospital
      cardiac arrest with a recorded 50-min interval before the restoration of
      spontaneous circulation. Multiple life threatening injuries were sustained and a
      profound peripheral neuropathy developed. Cognitively, he was remarkably intact.
      We document his acute admission and his recovery during an inpatient stay in a UK
      based Neurorehabilitation Unit. CONCLUSION: Intensive neurorehabilitation in this
      case improved functional independence and facilitated neuropsychological
      recovery, to the point that our patient was discharged to independent living.
      This case offers some support to the hypothesis that the electrical activity of a
      lightning strike can be both cardioprotective and neuroprotective, and that
      prolonged cardiopulmonary resuscitation is warranted in such cases.

PMID- 30182739
TI  - Development of an ELISA-LC-MS hybrid assay for quantification of biotherapeutics.
AB  - BACKGROUND: Magnetic bead immunocapture-LC-MS has been widely used for
      bioanalysis of biotherapeutic proteins. However, magnetic beads are difficult to
      be fully automated and more costly than ELISA plates. AIM: Develop an ELISA-LC-MS
      hybrid assay as an alternate platform. RESULTS: Among seven ELISA plates tested,
      Pierce streptavidin plates, which did not require time-consuming capture antibody
      precoating steps, provided the best sensitivity and assay dynamic range (5-2500
      ng/ml or 10-5000 ng/ml), similar to magnetic bead immunocapture-LC-MS assay and
      better than an ELISA (50-500 ng/ml). The entire procedures could be fully
      automated using a liquid handling system. CONCLUSION: This study demonstrates
      that ELISA-LC-MS hybrid approach using streptavidin plates represents a promising
      platform for bioanalysis of biotherapeutics.

PMID- 30182740
TI  - Mixed states in bipolar disorder: modelling, measuring and managing.
AB  - OBJECTIVE: To consider whether consensus exists in recommendations for managing
      bipolar mixed states published in recent reviews and treatment guidelines, and to
      summarise what might be their best management. CONCLUSION: Limitations to and
      changes in the definition of mixed states compromise diagnosis and management.
      The striking comparison between DSM-IV and DSM-5 criteria sets risks under
      diagnosis and over-diagnosis. Current reviews and guidelines offer limited
      evidence to guide treatment; however, management should involve addressing the
      contribution of any antidepressant medication, and the introduction of a second
      generation antipsychotic medication to stabilise the condition.

PMID- 30182741
TI  - Spirituality and its relationship with positive adjustment following traumatic
      brain injury: a scoping review.
AB  - OBJECTIVE: To identify the extent of research which has investigated spirituality
      or closely related meaning-making constructs after traumatic brain injury (TBI).
      DESIGN: A scoping review was employed to capture the broadest possible range of
      studies. METHODS: Search terms 'spirituality', 'religion', 'beliefs', 'faith',
      'hope', 'meaning', 'purpose in life', 'sense of coherence' and 'posttraumatic
      growth' were combined with search terms related to TBI. Findings were restricted
      to empirical studies published in English, in peer-reviewed journals and
      conducted over a 20-year period between 1997 and 2016. RESULTS: Nine studies were
      identified, conducted in the USA, Canada and the UK. These included eight
      quantitative studies and one qualitative study. Definitions and measurement of
      spirituality varied widely among the studies. Findings revealed that spirituality
      was closely related to a number of positive outcomes following TBI including
      psychological coping, physical health, mental health, productivity, life
      satisfaction, functional independence and posttraumatic growth. CONCLUSIONS: The
      limited research conducted into spirituality following TBI suggests it can play
      an important role in the recovery process. Further research is necessary to
      identify the particular spiritual needs of this population, and how clinical
      staff may be supported to address such needs.

PMID- 30182742
TI  - Fabrication of nanofiber coated with l-arginine via electrospinning technique: a
      novel nanomatrix to counter oxidative stress under crosstalk of co-cultured
      fibroblasts and satellite cells.
AB  - The objective of this study was to synthesize and characterize novel polyurethane
      (PU)-nanofiber coated with l-arginine by electrospinning technique. This study
      determined whether l-arginine conjugated with PU-nanofiber could stimulate cell
      proliferation and prevent H2O2-induced cell death in satellite cells co-cultured
      with fibroblasts isolated from Hanwoo (Korean native cattle). Our results showed
      that l-arginine conjugated with PU nanofiber could reduce cytotoxicity of co
      cultured satellite cells. Protein expression levels of bcl-2 were significantly
      upregulated whereas those of caspase-3 and caspase-7 were significantly
      downregulated in co-culture of satellite cells compared to those of monoculture
      cells after treatment with PU-nanofiber coated with l-arginine and which
      confirmed by Confocal microscope. These results suggest that co-culture of
      satellite cells with fibroblasts might be able to counter oxidative stress
      through translocation/penetration of antioxidant, collagen, and molecules
      secreted to satellite cells. Therefore, this nanofiber might be useful as a wound
      dressing in animals to counter oxidative stresses.

PMID- 30182743
TI  - Ambient dose during intra-oral radiography with current techniques: Part 2
      quantifying the remnant beam - an in vivo study.
AB  - OBJECTIVES:: (1) To find a safe reference transmission factor for the remnant
      beam to be used when assessing the remnant beam during intra-oral radiography.
      (2) To identify factors such as exposure type, side (left or right), gender and
      age that might significantly affect transmission. METHODS:: Measurements were
      performed in the remnant beam during 323 intra-oral exposures of 43 patients. The
      exposure parameters were 60 kV and 7 mA. These measurements were compared with
      values in the same setting, but without a patient present to arrive at a
      transmission value. Differences between types of exposure [bitewing (BW), incisor
      and canine (IC) periapical, premolar and molar (PM) periapical], exposure side
      (left or right), gender and age were statistically analysed. The reference value
      was based on the exposure yielding the highest transmission value, to which a
      safety margin of two standard deviations (SDs) was added, and then rounding up.
      RESULTS:: The respective mean transmission values (SD) for BW, IC and PM
      exposures were as follows: 1.78% (1.15%), 0.639% (0.63%) and 2.60% (0.98%). The
      differences between PM and IC and between BW and IC were significant (p > 0.01).
      The differences between exposure side, gender and age were not significant. The
      reference transmission value, which was calculated from the highest mean
      transmission percentage for PM (2.60%) plus twice the SD (0.98%) and rounding up,
      was 5%. CONCLUSIONS:: A transmission factor of 5% could be used to assess the
      remnant beam during intra-oral radiography. Anterior exposures led to
      significantly lower transmission values than posterior exposures.

PMID- 30182744
TI  - Comparison of manual and dose reduction modes of a MORITA R100 CBCT.
AB  - OBJECTIVE:: To compare effective dose differences when acquiring (1) dose
      reduction mode and (2) manual mode in a MORITA R100 CBCT. METHODS:: 24 exposure
      protocols with different technique factors were performed in both the dose
      reduction mode and the manual mode in a Veraviewepocs 3D R100 cone beam CT
      device. 48 TLD were placed in a RANDO head phantom at 24 different sites.
      Effective doses were calculated according to the formalism published in the 103rd
      ICRP report. RESULTS:: Effective doses for the dose reduction mode protocols
      ranged from 14 to 156 uSv [mean = 57 uSv, standard deviation (SD) = 37 uSv],
      whereas effective doses for the manual mode protocols ranged from 22 to 267 uSv
      (mean = 94 uSv, SD = 65 uSv). Thus, across all protocols, the dose reduction mode
      leads to a drop of the effective dose by 38 % (SD = 6 %). CONCLUSIONS:: The
      estimated effective doses are significantly lower if dose reduction protocols are
      acquired.

PMID- 30182745
TI  - Clinical and Radiologic Outcomes of the Matti-Russe Technique for Scaphoid
      Nonunions in Pediatric Patients.
AB  - BACKGROUND: Scaphoid fractures are a common injury, and a known complication is
      nonunion. One option to treat this nonunion is with the Matti-Russe technique,
      which takes a corticocancellous graft and fits it into the defect without
      internal fixation. The advent of modern methods of fixation has led the classic
      Matti-Russe technique to fall out of favor. In this study, we describe the
      classic technique and evaluate the results of the Matti-Russe method for
      treatment of scaphoid nonunions specifically for the pediatric population. Our
      purpose was to evaluate the long-term clinical and radiologic outcomes after
      surgery for scaphoid nonunion using the Matti-Russe technique in the pediatric
      population. METHODS: A retrospective review was performed of patients less than
      17 years of age, with a scaphoid nonunion that was treated with the Matti-Russe
      technique. This technique consisted of open reduction with intercalated bone
      graft and no internal fixation with hardware. Union was determined by
      radiographic evaluation. Computed tomography was obtained in 7 of 10 patients in
      this series and showed bony bridging in more than 50% of the scaphoid width in 3
      different views. Intrascaphoid, scapholunate, and radiolunate angles were
      calculated. We reviewed wrist range of motion and complications. We obtained
      postoperative Mayo and Disabilities of the Arm, Shoulder and Hand (DASH) scores.
      RESULTS: There were 10 patients who underwent the Matti-Russe technique. The
      average age was 14.7 years old (+/-1.34, range: 13-17). All 10 of these patients
      had a scaphoid waist nonunion. There were 9 males and 1 female with an average
      follow-up of 13 months. The average amount of time to surgery from the date of
      injury was 12.3 months. All 10 patients went on to radiographic union at or
      before 6 months from surgery. Preoperative intrascaphoid, scapholunate, and
      radiolunate angles were 29 degrees  (+/-5.38), 62 degrees  (+/-18.28), and 20
      degrees  (+/-9.22). Postoperative intrascaphoid, scapholunate, and radiolunate
      angles improved to 16 degrees  (+/-6.89), 38 degrees  (+/-8.50), and 10 degrees 
      (+/-4.69), which was significant. Seven out of 10 patients completed
      postoperative outcomes measures. The average postoperative Mayo wrist score was
      87.9 (+/-14.10, range: 60-100). The average postoperative DASH score was 1.9 (+/
      2.03, range: 0-4.5). There were no associated complications nor reoperations.
      CONCLUSION: The Matti-Russe technique is a safe and effective treatment for
      scaphoid nonunion in the pediatric population. It facilitates scaphoid union
      without the need for screw fixation and avoiding potential complications with
      hardware.

PMID- 30182746
TI  - Thirty-Day Outcomes Following Surgical Decompression of Thoracic Outlet Syndrome.
AB  - BACKGROUND: Surgical thoracic outlet syndrome (TOS) management involves
      decompression of the neurovascular structures by releasing the anterior and/or
      middle scalene muscles, resection of the first and/or cervical ribs, or a
      combination. Various surgical approaches (transaxillary, supraclavicular,
      infraclavicular, and transthoracic) have been used with varying rates of
      complications. The purpose of this study was to evaluate early postoperative
      outcomes following surgical decompression for TOS. We hypothesized that first
      and/or cervical rib resection would be associated with increased 30-day
      complications and health care utilization. METHODS: The American College of
      Surgeons National Surgical Quality Improvement Program database was reviewed for
      all TOS cases of brachial plexus surgical decompression in the region of the
      thoracic inlet from 2005 to 2013. RESULTS: There were 225 patients (68% females;
      mean age: 36.4 years +/- 12.1; 26% body mass index [BMI] ? 30). There were 205
      (91%) patients who underwent first and/or cervical rib resection (+/
      scalenectomy), and 20 (9%) underwent rib-sparing scalenectomy. Compared with rib
      sparing scalenectomy, rib resection was associated with longer operative time and
      hospital stays ( P < .001). In the 30 days postoperatively, 8 patients developed
      complications (rib-scalenectomy, n = 7). Only patients with rib resection
      returned to the operating room (n = 10) or were readmitted (n = 9). CONCLUSIONS:
      Early postoperative complications are infrequent after TOS decompression. Rib
      resection is associated with longer surgical times and hospital stays. Future
      studies are needed to assess the association between early and long-term
      outcomes, surgical procedure, and health care utilization to determine the cost
      effectiveness of the various surgical interventions for TOS.

PMID- 30182747
TI  - Sensitive and robust LC-MS/MS analysis of digoxin in human plasma through
      optimization of in-source adduct formation.
AB  - AIM: To develop and validate an LC-MS/MS assay for the quantification of digoxin
      in human plasma. An LLOQ of 10 pg/ml using a 100 MUl sample was required to
      support drug-drug interactions studies. RESULTS: Digoxin formed multiple
      precursor ions in positive and negative ESI and methods based on several of these
      have been reported previously. After screening viable precursor ions, we found
      the ammonium adduct gave the best combination of sensitivity and selectivity on
      our LC-MS/MS platform. Samples were extracted using a simple liquid-liquid
      procedure. CONCLUSION: The assay was successfully validation to current EMA
      guidelines. To the best of our knowledge the developed assay is the most
      sensitive published to date.

PMID- 30182748
TI  - Development of models to predict fish early-life stage toxicity from acute
      Daphnia magna toxicity$.
AB  - Herein, we propose models for predicting fish early-life stage (ELS) toxicity
      from acute Daphnia magna toxicity and various molecular descriptors.
      Specifically, eight models were developed with fathead minnow (Pimephales
      promelas) data and were validated against Japanese medaka (Oryzias latipes) data
      because the quantity of available Japanese medaka data is much smaller than the
      quantity of fathead minnow data. The training data set for the models consisted
      of ELS fathead minnow toxicity data for 77 chemicals; data for 67 of the 77
      chemicals originated from the OPP Pesticide Ecotoxicity Database of the US
      Environmental Protection Agency. The training data were biased toward pesticides.
      A simple quantitative activity-activity relationship (QAAR) model based on the
      correlation between fish ELS and acute Daphnia magna toxicities showed good
      predictivity for the chemicals in the external validation data set relative to
      the predictivities of the other models in this study. However, goodness-of-fit
      and robustness were better for quantitative structure-activity-activity
      relationship (QSAAR) models that included molecular descriptors (such as
      pesticide-related atoms and substructures as well as molecular weight and three
      dimensional-structure-based parameters). A battery approach involving the use of
      both the QAAR and the QSAARs might enhance the reliability of the estimated
      values and prevent underestimates.

PMID- 30182749
TI  - The effect of linguistic background on rapid number naming: implications for
      native versus non-native English speakers on sideline-focused concussion
      assessments.
AB  - OBJECTIVE: To determine if native English speakers (NES) perform differently
      compared to non-native English speakers (NNES) on a sideline-focused rapid number
      naming task. A secondary aim was to characterize objective differences in eye
      movement behaviour between cohorts. BACKGROUND: The King-Devick (KD) test is a
      rapid number-naming task in which numbers are read from left-to-right. This
      performance measure adds vision-based assessment to sideline concussion testing.
      Reading strategies differ by language. Concussion may also impact language and
      attention. Both factors may affect test performance. METHODS: Twenty-seven
      healthy  NNES and healthy NES performed a computerized KD test under high
      resolution video-oculography.  NNES also performed a Bilingual Dominance Scale
      (BDS) questionnaire to weight linguistic preferences (i.e., reliance on non
      English language(s)). RESULTS: Inter-saccadic intervals were significantly longer
      in  NNES (346.3 +/- 78.3 ms vs. 286.1 +/- 49.7 ms, p = 0.001), as were KD test
      times (54.4 +/- 15.1 s vs. 43.8 +/- 8.6 s, p = 0.002). Higher BDS scores,
      reflecting higher native language dominance, were associated with longer inter
      saccadic intervals in  NNES. CONCLUSION: These findings have direct implications
      for the assessment of athlete performance on vision-based and other verbal
      sideline concussion tests; these results are particularly important given the
      international scope of sport. Pre-season baseline scores are essential to
      evaluation in the event of concussion, and performance of sideline tests in the
      athlete's native language should be considered to optimize both baseline and post
      injury test accuracy.

PMID- 30182750
TI  - CT texture analysis of the liver for assessing hepatic fibrosis in patients with
      hepatitis C virus.
AB  - OBJECTIVE:: To evaluate CT texture analysis (CTTA) for non-invasively staging of
      hepatic fibrosis (stages F0-F4) in a cohort of patients with hepatitis C virus
      (HCV). METHODS:: Quantitative texture analysis of the liver was performed on
      abdominal multidimensional CT scans. Single slice region of interest measurements
      of the total liver, Couinaud segments IV-VIII and segments I-III were made. CT
      texture parameters were tested against stage of hepatic fibrosis in segments IV
      VIII on the portal venous phase. Texture parameters were correlated with biopsy
      performed within 1 year for all cases with intermediate fibrosis (F0-F3).
      RESULTS:: CT scans of 556 adults (360 males, 196 females; mean age, 49.8 years),
      including a healthy control group (F0, n = 77) and patients with hepatitis C
      virus and Stage 0 disease (n = 49), and patients with increasing stages of
      fibrosis (F1, n = 80; F2 n = 99; F3 n = 87; F4 n = 164) were evaluated. Mean gray
      level intensity increased with increasing fibrosis. For significant fibrosis
      (>=F2), mean showed receiver operatingcharacteristic area under the curve (AUC)
      of 0.80 with sensitivity and specificity of 74 and 75% using a threshold of 0.44,
      with similar receiver operatingcharacteristic AUC and sensitivity/specificity for
      advanced fibrosis (>=F3). Skewness and kurtosis were inversely associated with
      hepatic fibrosis, most prominently in cirrhotic patients. A multivariate model
      combining these four texture features (mean, mpp, skewness and kurtosis) showed
      slightly improved performance with AUC of 0.82, 0.82 and 0.86 for any fibrosis
      (F0 vs F1-F4), significant fibrosis (F0-1 vs F2-4) and advanced fibrosis (F0-2 vs
      F3-4) respectively. CONCLUSION:: CT texture features may be associated with
      hepatic fibrosis and have utility in staging fibrosis, particularly at advanced
      levels. ADVANCES IN KNOWLEDGE:: CTTA may be helpful in detecting and staging
      hepatic fibrosis, particularly at advanced levels. CT measures like CTTA can be
      retrospectively evaluated without special equipment.

PMID- 30182751
TI  - Resting EEG Measures of Brain Arousal in a Multisite Study of Major Depression.
AB  - Several studies have found upregulated brain arousal during 15-minute EEG
      recordings at rest in depressed patients. However, studies based on shorter EEG
      recording intervals are lacking. Here we aimed to compare measures of brain
      arousal obtained from 2-minute EEGs at rest under eyes-closed condition in
      depressed patients and healthy controls in a multisite project-Establishing
      Moderators and Biosignatures of Antidepressant Response for Clinical Care
      (EMBARC). We expected that depressed patients would show stable and elevated
      brain arousal relative to controls. Eighty-seven depressed patients and 36
      healthy controls from four research sites in the United States were included in
      the analyses. The Vigilance Algorithm Leipzig (VIGALL) was used for the fully
      automatic classification of EEG-vigilance stages (indicating arousal states) of 1
      second EEG segments; VIGALL-derived measures of brain arousal were calculated. We
      found that depressed patients scored higher on arousal stability ( Z = -2.163, P
      = .015) and A stages (dominant alpha activity; P = .027) but lower on B1 stages
      (low-voltage non-alpha activity, P = .008) compared with healthy controls. No
      significant group differences were observed in Stage B2/3. In summary, we were
      able to demonstrate stable and elevated brain arousal during brief 2-minute
      recordings at rest in depressed patients. Results set the stage for examining the
      value of these measures for predicting clinical response to antidepressants in
      the entire EMBARC sample and evaluating whether an upregulated brain arousal is
      particularly characteristic for responders to antidepressants.

PMID- 30182752
TI  - Use of renal replacement therapy after out-of-hospital cardiac arrest in Denmark
      2005-2013.
AB  - OBJECTIVES: Renal replacement therapy (RRT) is used to treat acute kidney injury
      as part of multi organ failure. Use and prognostic implications after out-of
      hospital cardiac arrest (OHCA) is not well known. This study aims to assess
      incidence and use of RRT and whether RRT post-arrest was associated with 30-day
      mortality in Denmark in the years 2005-2013. METHODS: The Danish Cardiac Arrest
      Registry holds information on all OHCA patients in Denmark from 2005 to 2013. We
      identified 3,012 one-day survivors of OHCA >=18 years, with presumed cardiac
      aetiology of arrest, admitted to ICU without previous RRT. Change in use of RRT
      during the study period was assessed using competing risk analysis. Mortality was
      assessed with Cox regression. RESULTS: On average, RRT was performed in 6% of the
      patient population with an average annual 1% increase, HR: 1.01, CI: 0.95-1.07, p
      = .69. Hazard of RRT was lower in patients receiving bystander cardiopulmonary
      resuscitation (CPR) (p < .001), patients with a shockable primary rhythm (p =
      .009) and elderly patients (p = .03). Socioeconomic factors did not influence
      hazard of RRT, but patients admitted to tertiary centres had higher hazard of RRT
      (p = .009). Use of RRT was associated with increased mortality in multivariate
      Cox regression (HR: 1.28, CI: 1.06-1.55, p = .01). CONCLUSION: Use of RRT as part
      of post resuscitation care following OHCA did not increase from 2005 to 2013; use
      was more common in tertiary centres and in patients with negative prehospital
      predictors (no bystander CPR, non-shockable rhythm). RRT was associated with
      increased mortality.

PMID- 30182753
TI  - A randomized, double-blinded, placebo-controlled, parallel trial of vitamin D3
      supplementation in adult patients with migraine.
AB  - BACKGROUND: Vitamin D levels have been linked to certain pain states, including
      migraine. This study investigated whether vitamin D supplementation would be
      beneficial for adult patients with migraine (ClinicalTrials.gov Identifier:
      NCT01695460). METHODS: A randomized, double-blinded, placebo-controlled parallel
      trial was conducted in migraine patients (36 women and 12 men, 18-65 years of
      age). A 4-week baseline period was conducted before randomization to 24 weeks of
      treatment. Participants were assigned to receive D3-Vitamin (n = 24, 18 women and
      6 men, 100 MUg/day D3-Vitamin) or placebo (n = 24, 18 women and 6 men). Migraine
      attacks and related symptoms were assessed by self-reported diaries. The response
      rate (i.e. experiencing a 50% or greater reduction in migraine frequency from
      baseline to week 24), change in migraine severity, and number of migraine days
      were recorded. Changes in migraine-related symptoms, HIT-6TM scores, and pain
      sensitivity tests (pressure pain threshold and temporal summation) were also
      evaluated. Serum levels of both 25 (OH)D and 1,25 (OH)2D were assessed from
      baseline to week 24. RESULTS: The number of headache days changed from 6.14 +/-
      3.60 in the treatment group and 5.72 +/- 4.52 in the placebo group at baseline to
      3.28 +/- 3.24 and 4.93 +/- 3.24 by the end of the trial, respectively. Migraine
      patients on D3-Vitamin demonstrated a significant decrease (p < .001) in migraine
      frequency from baseline to week 24 compared with placebo. However, migraine
      severity, pressure pain thresholds, or temporal summation did not show a
      significant change. 25(OH)D levels increased significantly for the D3-Vitamin
      group during the first 12 weeks of treatment. There was no significant change in
      1,25(OH)2D. No side-effects were reported or noted. CONCLUSIONS: D3-Vitamin was
      superior to placebo in reducing migraine days in migraine patients. Larger
      studies are required to confirm that vitamin D3 might be one of the prophylactic
      options for adult patients with migraine.

PMID- 30182754
TI  - Resuming Publication of an Established Journal, Part 2.

PMID- 30182755
TI  - Stakeholder perspectives for possible residual limb monitoring system for persons
      with lower-limb amputation.
AB  - PURPOSE: To gather ideas from lower-limb prosthesis users and certified
      prosthetists regarding possible residual limb monitoring system features and data
      presentation. We also gathered information on the type of residual limb problems
      typically encountered, how they currently manage those problems, and their ideas
      for methods to better manage them. MATERIALS AND METHODS: Two focus groups were
      held; one with certified prosthetists and another with lower-limb prosthesis
      users. Open-ended questions were used in a moderated discussion that was audio
      recorded, transcribed, and assessed using applied thematic analysis. RESULTS AND
      CONCLUSIONS: Seven individuals participated in each focus group. Prosthetists
      came from a mix of practice settings, while prosthesis users were diverse in
      level of amputation, aetiology, and years of experience using lower-limb
      prostheses. Residual limb problems reported by participants were consistent with
      those in the literature. Participants suggested better managing residual limb
      problems through improved education, better detection of residual limb problems,
      and using sensor-based information to improve prosthetic technology. Participants
      favoured short-term use of a possible residual limb monitoring systems to
      troubleshoot residual limb problems, with temperature and pressure the most
      frequently mentioned measurements. Participants described that an ideal residual
      limb monitoring system would be lightweight, not interfere with prosthesis
      function, and result in benefits with regard to prosthetic care and socket
      function that outweighed inconveniences or concerns regarding system use. A
      potential positive of system use included having objective data for reimbursement
      justification, although it was pointed out that the residual limb monitoring
      system itself also needed to be reimbursable. Implications for Rehabilitation
      Stakeholders suggested better managing residual limb problems through improved
      education, better detection of residual limb problems, and using sensor-based
      information to improve prosthetic technology. Stakeholders favored short-term use
      of a possible system to troubleshoot residual limb problems, with temperature and
      pressure the most frequently mentioned measurements. Stakeholders described that
      an ideal residual limb monitoring system would be lightweight, not interfere with
      prosthesis function, and result in benefits with regard to prosthetic care and
      socket function that outweighs any inconveniences or concerns regarding system
      use. Stakeholders indicated that a potential positive of system use included
      having objective data for reimbursement justification, although it was pointed
      out that the residual limb monitoring system itself also needed to be
      reimbursable.

PMID- 30182756
TI  - Risk of chemotherapy-induced febrile neutropenia with early discontinuation of
      pegfilgrastim prophylaxis: a retrospective evaluation using Medicare claims.
AB  - BACKGROUND: Two recent evaluations reported that many cancer chemotherapy
      patients discontinue pegfilgrastim prophylaxis (PP) following the first cycle,
      and that these patients have a higher subsequent risk of febrile neutropenia
      (FN). Such evidence is based principally on the experience of younger adults with
      private healthcare coverage, and the generalizability of results to elderly
      Medicare patients is unknown. METHODS: A matched-cohort design and data from the
      Medicare Claims Research Identifiable Files were employed. The source population
      comprised cancer patients aged >=65 years who received chemotherapy with
      intermediate/high-risk for FN and first-cycle PP. From the source population,
      beginning with the second cycle, all patients who received PP in all previous
      cycles were identified. From this sub-set, patients who did not receive PP in the
      cycle of interest ("comparison patients") were matched to those who received PP
      in that cycle ("PP patients"); the same process was repeated for subsequent
      cycles. Odds ratios (OR) for FN (broad and narrow definitions) were estimated
      using generalized estimating equations. RESULTS: Among 77,616 elderly patients in
      the source population, 5.3% did not receive second-cycle PP and were matched to
      those who did. In cycle 2, FN odds were significantly higher among comparison
      patients vs PP patients when employing the broad definition (OR = 1.9, p < .001)
      and the narrow definition (OR = 2.1, p < .001). Results for subsequent cycles
      (broad definition: OR = 2.0, p < .001; narrow definition: OR = 2.1, p < .001) and
      for the last cycle (broad definition: OR = 1.4, p = .060; narrow definition: OR =
      1.7, p = .055) were largely comparable. CONCLUSIONS: In this large-scale
      evaluation of elderly Medicare patients who received myelosuppressive
      chemotherapy and first-cycle PP in recent US clinical practice, FN risk was
      substantially lower among patients who continued to receive PP in subsequent
      cycles vs those who discontinued PP.

PMID- 30182758
TI  - Are people with lower limb amputation changing? A seven-year analysis of patient
      characteristics at admission to inpatient rehabilitation and at discharge.
AB  - PURPOSE: What are the characteristics of people with lower limb amputation at
      admission to, and discharge from, subacute rehabilitation? Have these
      characteristics changed over time? METHODS: A total of 425 lower limb amputation
      inpatient rehabilitation admissions (335 individuals) from 2005 to 2011 were
      examined. Admission characteristics, including aetiology, gender, age, amputation
      level, cognition (Mini-Mental State Examination (MMSE)), indoor mobility aid,
      motor function (Functional Independence Measure motor subscale) and number and
      type of comorbidities, and discharge characteristics, including prosthetic
      prescription, motor function, discharge mobility aid, and destination were
      compared by admission date and year. RESULTS: Proportion of people with lower
      limb amputation with nonvascular aetiology increased over time (2004, 15% to
      2011, 24%) (beta = -181.836, p < 0.001). Admission cognition increased over time
      (beta = 9.296, p < 0.001). Motor function worsened over time; median admission
      (IQR) Functional Independence Measure motor 70 (59-77) in 2005 to 67 (51.5-73.25)
      in 2011 (beta = -1.937, p < 0.001) and discharge from 81 in 2005 to 79 in 2011
      (beta = -1.267, p < 0.001). Prosthetic prescription rates were highest in 2005
      (68%) decreasing to 47% in 2010 (beta = -200.473, p < 0.001). CONCLUSIONS: Total
      numbers of people with lower limb amputation did not change over the seven-year
      study period. Changes were observed in aetiology, cognition and motor function.
      Prosthetic prescription rates decreased over time. Implications for
      rehabilitation Rehabilitation should account for the changing characteristics of
      people with lower limb amputation. Motor function should be addressed as part of
      rehabilitation to optimise the patient's ability to return home and to the
      community. Prescription rates for lower limb prostheses reduced across time,
      indicating more specific selection processes and refined clinical decision
      making; this decision is best informed by a multi-disciplinary approach.

PMID- 30182757
TI  - Touch-actuated microneedle array patch for closed-loop transdermal drug delivery.
AB  - To date, only approximately 20 drugs synthesized with small molecules have been
      approved by the FDA for use in traditional transdermal patches (TTP) owing to the
      extremely low permeation rate of the skin barrier for macromolecular drugs. A
      novel touch-actuated microneedle array patch (TMAP) was developed for transdermal
      delivery of liquid macromolecular drugs. TMAP is a combination of a typical TTP
      and a solid microneedle array (MA). High doses of liquid drug formulations,
      especially heat-sensitive compounds can be easily filled and stored in the drug
      reservoir of TMAPs. TMAP can easily penetrate the skin and automatically retract
      from it to create microchannels through the stratum corneum (SC) layer using
      touch-actuated 'press and release' actions for passive permeation of liquid
      drugs. Comparison of subcutaneous injection, TTP, solid MA, and dissolvable MA,
      indicated that insulin-loaded TMAP exhibited the best hypoglycemic effect on type
      1 diabetic rats. A 'closed-loop' permeation control was also provided for on
      demand insulin delivery based on feedback of blood glucose levels (BGLs). Twenty
      IU-insulin-loaded TMAP maintained the type 1 diabetic rats in a normoglycemic
      state for approximately 11.63 h, the longest therapeutic duration among all
      previously reported results on microneedle-based transdermal patches. TMAP
      possesses excellent transdermal drug delivery capabilities.

PMID- 30182759
TI  - Posttraumatic stress disorder symptom clusters and substance use among patients
      with upper limb amputations due to traumatic injury.
AB  - PURPOSE: Examining the relationship between posttraumatic stress disorder and
      posttraumatic stress disorder symptom clusters (re-experiencing, avoidance,
      hyperarousal, emotional numbing) on three substance use measures among
      individuals with upper limb amputation due to traumatic injury - an understudied
      population with high rates of posttraumatic stress disorder. METHODS: Multi-site,
      cross-sectional design. Participants (N = 236) were recruited from seven
      prosthetic rehabilitation centres across the USA and completed measures of PTSD,
      alcohol use, prescription medication overuse, and illicit drug use. RESULTS:
      Twenty-six percent of participants screened positive for posttraumatic stress
      disorder, 39% for problematic alcohol use, 12% for prescription medication
      overuse, and 7% for illicit drug use. No association was found between
      posttraumatic stress disorder or posttraumatic stress disorder symptoms clusters
      on problematic alcohol use. However, hyperarousal symptoms increased odds of
      overusing prescription medication (odds ratio = 3.30); further, a positive screen
      for posttraumatic stress disorder increased odds of illicit drug use (odds ratio
      = 2.95). CONCLUSIONS: These findings demonstrate the importance of assessing
      psychological well-being and a variety of substance use behaviours following
      amputation from traumatic injury. These findings may also provide clinically
      relevant targets for prevention and intervention regarding prescription
      medication and illicit substance use, such as incorporating evidence-based
      treatment for posttraumatic stress disorder hyperarousal symptoms (e.g.,
      prolonged exposure) and/or integrated treatment for posttraumatic stress
      substance misuse (e.g., Seeking Safety) into patients' long-term
      inpatient/outpatient rehabilitation plans. Implications for rehabilitation
      Posttraumatic stress disorder hyperarousal symptoms increased odds of overusing
      prescription medication among individuals with upper limb amputation due to
      traumatic injury; a positive screen for posttraumatic stress disorder increased
      odds of illicit drug use. Psychological assessments should be incorporated into
      treatment and rehabilitation plans following amputation from traumatic injury.
      Rehabilitation specialists should consider adding or integrating evidence-based
      treatment for posttraumatic stress disorder into patients' long-term
      rehabilitation plan to reduce risk for problematic substance use. Findings
      support calls by the Centre for Disease Control and Prevention to overhaul
      prescription medication guidelines, including the need to assess risk and address
      harms concerning overuse of prescription medication.

PMID- 30182760
TI  - Managing limb pain using virtual reality: a systematic review of clinical and
      experimental studies.
AB  - PURPOSE: The aim of this systematic review was to assess the effect of virtual
      representation of body parts on pain perception in patients with pain and in pain
      free participants exposed to experimentally induced pain. METHODS: Databases
      searched: Medline, PsycInfo, CINAHL, and Web of Science. Studies investigating
      participants with clinical pain or those who were pain free and exposed to
      experimentally induced pain were analysed separately. RESULTS: Eighteen clinical
      studies and seven experimental studies were included. Randomised controlled
      clinical trials showed no significant difference between intervention and control
      groups for pain intensity. Clinical studies with a single group pretest-posttest
      design showed a reduction in pain after intervention. In the studies including a
      sample of pain free participants exposed to experimentally induced pain there was
      an increase in pain threshold when the virtual arm was collocated with the real
      arm, when it moved in synchrony with the real arm, and when the colour of the
      stimulated part of the virtual arm became blue. Observing a virtual arm covered
      with iron armour reduced pain. CONCLUSIONS: The use of virtual representations of
      body parts to reduce pain is promising. However, due to the poor methodological
      quality and limitations of primary studies, we could not find conclusive
      evidence. Implications for rehabilitation Virtual reality has been increasingly
      used in the rehabilitation of painful and dysfunctional limbs. Virtual reality
      can be used to distract attention away from acute pain and may also provide
      corrective psychological and physiological environments. Virtual representation
      of body parts has been used to provide a corrective re-embodiment of painful
      dysmorphic body parts, and primary research shows promising results.

PMID- 30182761
TI  - A subset of patients with acquired partial lipodystrophy developing severe
      metabolic abnormalities.
AB  - : Purpose/Aim of the study: Acquired partial lipodystrophy (APL) is a rare
      disease characterized by selective loss of adipose tissue. In this study, we
      aimed to present a subset of patients with APL, who developed severe metabolic
      abnormalities, from our national lipodystrophy registry. MATERIALS AND METHODS:
      Severe metabolic abnormalities were defined as: poorly controlled diabetes (HbA1c
      above 7% despite treatment with insulin more than 1 unit/kg/day combined with
      oral antidiabetics), severe hypertriglyceridemia (triglycerides above 500 mg/dL
      despite treatment with lipid-lowering drugs), episodes of acute pancreatitis, or
      severe hepatic involvement (biopsy-proven non-alcoholic steatohepatitis (NASH)).
      RESULTS: Among 140 patients with all forms of lipodystrophy (28 with APL), we
      identified 6 APL patients with severe metabolic abnormalities. The geometric mean
      for age was 37 years (range: 27-50 years; 4 females and 2 males). Five patients
      had poorly controlled diabetes despite treatment with high-dose insulin combined
      with oral antidiabetics. Severe hypertriglyceridemia developed in five patients,
      of those three experienced episodes of acute pancreatitis. Although all six
      patients had hepatic steatosis at various levels on imaging studies, NASH was
      proven in two patients on liver biopsy. Our data suggested that APL patients with
      severe metabolic abnormalities had a more advanced fat loss and longer disease
      duration. CONCLUSIONS: We suggest that these patients represent a potential
      subgroup of APL who may benefit from metreleptin or investigational therapies as
      standard treatment strategies fail to achieve a good metabolic control.

PMID- 30182762
TI  - Ischemic QRS prolongation as a predictor of ventricular fibrillation in a canine
      model.
AB  - OBJECTIVES: An acute coronary occlusion and its possible subsequent complications
      is one of the most common causes of death. One such complication is ventricular
      fibrillation (VF) due to myocardial ischemia. The severity of ischemia is related
      to the amount of coronary arterial collateral flow. In dog studies collateral
      flow has also been shown to be associated with QRS prolongation. The aim of this
      study was to investigate whether ischemic QRS prolongation (IQP) is associated
      with impending VF in an experimental acute ischemia dog model. METHODS: Degree of
      IQP and occurrence of VF were measured in dogs (n = 21) during coronary occlusion
      for 15 min and also during subsequent reperfusion (experiments conducted in
      1984). RESULTS: There was a significant difference in absolute IQP between dogs
      which developed VF during reperfusion (47 +/- 29 ms, mean +/- SD) and those which
      did not (12 +/- 10 ms; p = .001). CONCLUSIONS: IQP during acute coronary
      occlusion is associated with reperfusion VF in an experimental dog model and
      might therefore be a potential predictor of malignant arrhythmias in patients
      with acute coronary syndrome.

PMID- 30182763
TI  - Interferon-based treatment is superior to nucleos(t)ide analog in reducing HBV
      related hepatocellular carcinoma for chronic hepatitis B patients at high risk.
AB  - BACKGROUND: The effect of nucleos(t)ide analogs (NAs) versus interferon (IFN) on
      the occurrence of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) is
      controversial. We assessed whether antiviral strategy affected HCC development in
      CHB patients at different HCC risks. METHODS: 1112 CHB patients with antiviral
      therapy were included in this retrospective study. Patients treated with NAs only
      were classified into NAs group (n = 682) while those received IFN treatment with
      or without NAs were defined as IFN group (n = 430). Propensity score matching
      (PSM) was applied to minimize baseline differences. RESULTS: Totally, 31 patients
      developed HCC during follow-up (median 5.41 years). The cumulative HCC incidence
      at 10 years was significantly lower in the IFN group than NAs group (2.7% vs
      8.0%, p < 0.001). Similar results were obtained in the PSM-cohort. Patients with
      IFN-based treatment were less likely to develop HCC than those with NAs (Hazard
      ratio = 0.15; 95% CI 0.04-0.66; p = 0.012). Subgroup analyses demonstrated that
      this superiority of IFN in reducing HCC development was obvious in patients at
      high- but not low-risk of HCC. CONCLUSIONS: Reduction of HCC development was more
      significant in CHB patients at higher HCC risk with IFN-based therapy than NAs
      treatment.

PMID- 30182764
TI  - A pilot trial of metformin for insulin resistance and mood disturbances in
      adolescent and adult women with polycystic ovary syndrome.
AB  - We examine the effects of metformin on insulin resistance (IR) and mood including
      in adolescent and adult women with polycystic ovary syndrome (PCOS). This trial
      was conducted in 19 adolescents (age <=18 years) and 25 adult (age >18 years)
      women with PCOS. Anthropometric and measurements including, serum glucose,
      endocrine panel, and lipid profile were performed at baseline. IR was measured by
      Homeostasis Model Assessment IR (HOMA-IR). Anxiety and depression were measured
      by Beck's Anxiety (BAI) and Depression Inventories (BDI-II). All tests were
      repeated after a 90-day treatment with metformin (1,500 mg/day). The severity of
      depression and anxiety decreased after 90-day treatment with metformin in women
      diagnosed with PCOS. The BAI scores were higher in adolescent group while BDI-II
      scores were higher in the adult group (p = .016). After 90-day metformin
      treatment, both BDI-II and BAI scores were decreased by 3.3 and 3.4, respectively
      (p < .001). Indicators of IR and obesity were improved with this therapy.
      Although the adolescents weighed lower than the adults, baseline HOMA-IR 5.5 +/-
      1.7 was higher in this group than 4.4 +/- 1.2 in the adult women (p =.022). The
      findings suggest that metformin decrease IR and improve mood both in adolescent
      and adult women with PCOS.

PMID- 30182765
TI  - Fifty years my mentor: Harold Atwood.
AB  - While readers of Journal of Neurogenetics may be familiar with Harold Atwood's
      work with Drosophila, most may know little of his previous work on crustacean
      neuromuscular systems that prepared him to utilise Drosophila neuromuscular
      junctions. Here, I will give brief overviews of his academic career, one line of
      his research that persisted throughout his career and his entry to the Drosophila
      field. This is not a review paper. Finally, I will relate my experiences with
      Atwood since 1967 as an undergraduate, Postdoctoral Fellow, and Faculty member
      and finish with some personal anecdotal observations.

PMID- 30182767
TI  - ILK enhances migration and invasion abilities of human endometrial stromal cells
      by facilitating the epithelial-mesenchymal transition.
AB  - Epithelial-mesenchymal transition (EMT) plays a significant part in the
      pathogenesis of endometriosis by facilitating the migration and invasion
      abilities of cells. Integrin-linked kinase (ILK) increases the cell migration and
      invasion abilities by inducing the EMT. Eutopic and control endometrial stromal
      cells (EuSCs and CSCs) were isolated and cultured. Cell migration and invasion
      abilities were detected by transwell assays. Levels of proteins were detected by
      Western blot. EuSCs showed higher levels of ILK, N-cadherin, vimentin and
      stronger migration and invasion abilities. After transfection of siRNA-ILK, E
      cadherin and keratin levels were increased while N-cadherin and vimentin levels
      were decreased in EuSCs. Besides that, the migration and invasion abilities of
      EuSCs were significantly decreased after transfection of siRNA-ILK. On the
      contrary, levels of ILK, N-cadherin and vimentin were increased while levels of E
      cadherin and keratin were decreased simultaneously after transfecting CSCs with
      pEGFP-C1-ILK. Simultaneously, the migration and invasion abilities of CSCs were
      increased after transfection of pEGFP-C1-ILK. Our study verified that high
      expression of ILK enhanced the migration and invasion abilities of ESCs by
      facilitating the EMT. Given that ILK played crucial roles in the pathogenesis of
      endometriosis, it may be considered as a promising targeted therapy for
      endometriosis.

PMID- 30182766
TI  - Insights into possibilities for grouping and read-across for nanomaterials in EU
      chemicals legislation.
AB  - This paper presents a comprehensive review of European Union (EU) legislation
      addressing the safety of chemical substances, and possibilities within each piece
      of legislation for applying grouping and read-across approaches for the
      assessment of nanomaterials (NMs). Hence, this review considers both the
      overarching regulation of chemical substances under REACH (Regulation (EC) No
      1907/2006 on registration, evaluation, authorization, and restriction of
      chemicals) and CLP (Regulation (EC) No 1272/2008 on classification, labeling and
      packaging of substances and mixtures) and the sector-specific pieces of
      legislation for cosmetic, plant protection and biocidal products, and legislation
      addressing food, novel food, and food contact materials. The relevant supporting
      documents (e.g. guidance documents) regarding each piece of legislation were
      identified and reviewed, considering the relevant technical and scientific
      literature. Prospective regulatory needs for implementing grouping in the
      assessment of NMs were identified, and the question whether each particular piece
      of legislation permits the use of grouping and read-across to address information
      gaps was answered.

PMID- 30182769
TI  - Association of luteinizing hormone/choriogonadotropin receptor gene polymorphisms
      with polycystic ovary syndrome risk: a meta-analysis.
AB  - To investigate the association between Luteinizing hormone/choriogonadotropin
      receptor (LHCGR) gene polymorphisms and polycystic ovary syndrome (PCOS). A
      systematic literature search and meta-analysis using STATA software for included
      studies. Fourteen case-control studies containing rs13405728, rs4539842, and
      rs2293275 of LHCGR gene were included, which was comprised of 11,738 PCOS cases
      and 35,329 controls. Results of the meta-analysis showed a significant
      association between PCOS and rs13405728 (for G vs. A: OR = 0.735, 95% CI = 0.699
      0.773, p<.001; For GG vs. AG + AA: OR = 0.578, 95% CI = 0.436-0.767, p<.001; For
      GG + AG vs. AA: OR = 0.817, 95% CI = 0.741-0.901, p<.001) in Asian populations,
      and rs4539842 (for ins/ins vs. ins/non + non/non: OR = 0.686, 95% CI = 0.483
      0.974, p=.035) and rs2293275 (for AA vs. AG + GG: OR = 4.115, 95% CI = 1.033
      16.38, p=.045) in Caucasian populations, respectively. LHCGR gene variations are
      population specifically associated with PCOS, which indicated these SNPs in LHCGR
      may contribute to the pathogenesis of PCOS and could be used as potential
      biomarkers to predict the risk of PCOS.

PMID- 30182768
TI  - Association between insurance type and pregnancy outcomes in women diagnosed with
      hypertensive disorders of pregnancy.
AB  - OBJECTIVE: Hypertension in pregnancy is associated with adverse maternal and
      neonatal outcomes. Previous studies have demonstrated disparities in the risk of
      preeclampsia based on race, educational attainment, census tract income level and
      household income. Yet, data on the association of insurance type, classification
      of hypertension in pregnancy and outcomes have not been well described. We sought
      to compare outcomes in women with hypertensive disorders of pregnancy, by private
      versus public insurance. STUDY DESIGN: This was a retrospective cohort study of
      subjects with a hypertensive disorder of pregnancy that delivered >=23-week
      gestation at Oregon Health & Science University (October 2013-December 2017). The
      cohort began with the 2013 American College of Obstetricians and Gynecologists
      Executive Summary on Hypertension in Pregnancy, which advised surveillance for
      severe features of disease in women with hypertension. Utilizing ICD-9 and ICD-10
      discharge codes, followed by individual chart review, subjects were stratified
      into two groups by insurance status: Medicaid (public insurance), or individual
      or group health insurance (private insurance). As primary outcomes, we assessed
      severe features of preeclampsia, adverse maternal or neonatal outcomes
      (composite), and final hypertensive diagnosis: (i) chronic hypertension; (ii)
      gestational hypertension; (iii) preeclampsia without severe features and, (iv)
      preeclampsia with severe features. Differences in demographic and outcome data
      were analyzed by chi-square, t-test, and logistic regression. RESULTS: Among 10
      132 deliveries, 1335 (13.2%) were delivered with a hypertensive disorder of
      pregnancy. Medicaid covered 54.1% (722) of these deliveries; 44.1% (589) were
      covered by private insurance, and 1.8% (24) had unknown insurance. There was a
      similar percentage of subjects with Medicaid or private insurance in each
      hypertensive group (p = .08). However, compared to subjects with private
      insurance, those with Medicaid had more severe blood pressure (BP) elevations
      (systolic BP >=160 mmHg, p = .001) and more cases of eclampsia (p = .04), while
      neonates of subjects with Medicaid had more intensive care unit admissions (p =
      .02), and preterm births (p < .001). The association between Medicaid insurance
      and severe BP elevation, or adverse neonatal outcomes, persisted after
      multivariable adjustment. CONCLUSION: Medicaid was not associated with a
      particular hypertensive disorder in pregnancy, yet those with Medicaid
      experienced more severe BP elevations and higher rates of adverse neonatal
      outcomes. More research is needed to understand potential risk factors and ways
      to improve outcomes for those with publicly funded insurance.

PMID- 30182770
TI  - Evaluation of toxicological and teratogenic effects of carbosilane glucose
      glycodendrimers in zebrafish embryos and model rodent cell lines.
AB  - Glycodendrimers (Glyco-DDMs) represent a rapidly growing class of nanoparticles
      with promising properties for biomedical applications but concerns regarding the
      impact on human health and environment are still justified. Here we report, for
      the first time, the comparative study of in vivo developmental toxicity of
      carbosilane Glyco-DDMs and their cytotoxicity in vitro. Carbosilane Glyco-DDMs
      (generation 1-3) containing 4, 8, and 16 beta-d-glucopyranosyl units at the
      periphery (DDM1Glu, DDM2Glu, and DDM3Glu) were synthesized and characterized by
      1H, 13C and 29Si NMR, mass spectrometry, dynamic light scattering, atomic force
      microscopy (AFM), and computer modeling. In vitro cytotoxicity assay (MTT) of
      DDM1-3Glu was performed on three different rodent cell lines (Cricetulus griseus)
      - B14 (ATCC, CCL-14.1), BRL 3A (ATCC, CRL-1442), and NRK 52E (ATCC, CRL-1571).
      Overall, very low cytotoxicity was observed with calculated IC50 in mM range with
      slight difference between each cell line and DDM generation investigated.
      Modified fish embryo test (FET) was further used for DDM3Glu developmental
      toxicity testing on zebrafish (Danio rerio) embryos. While seemingly harmless to
      intact embryos, adverse effects of DDMs on the embryonic development become
      evident after chorion removal (LD50=2.78 uM at 96 hpe). We summarized that the
      modified FET test showed a two to three orders of magnitude difference between
      the in vitro cytotoxicity and in vivo developmental toxicity of DDM3Glu. While,
      in general, the Glyco-DDMs show great promises as efficient vectors in targeted
      drug delivery or as therapeutic molecules itself, we suggest that their
      developmental toxicity should be thoroughly investigated to exclude safety risks
      associated with their potential biomedical use.

PMID- 30182771
TI  - Polymorphisms in vitamin D receptor gene, but not vitamin D levels, are
      associated with polycystic ovary syndrome in Brazilian women.
AB  - This study aimed to investigate the association between vitamin D (VitD) levels,
      polymorphisms in VDR gene (ApaI, BsmI, FokI, and TaqI) and the polycystic ovary
      syndrome (PCOS) in a group of Brazilian women. A total of 100 patients with PCOS
      and 100 control women were included. The quantification of 25-hydroxyvitamin D
      (25(OH)D) was performed in high-performance liquid chromatography (HPLC).
      Polymorphisms on VDR gene were performed by PCR-RFLP. The BsmI AG genotype was
      more frequent in PCOS group, while the GG genotype was more frequent in the
      control group (p = .007). The frequency of the Taql CC genotype was higher in
      PCOS group, while the CT genotype was the most frequent in the control group (p =
      .021). Mean serum VitD levels were similar between the groups. However, there was
      a negative correlation between VitD levels and Ferriman-Gallwey score (p = .031,
      r = -.260) in the PCOS group. The TaqI and BsmI polymorphisms were associated
      with PCOS. Moreover, VitD levels are associated with the clinical
      hyperandrogenism. The data suggest the role of VitD in PCOS development and its
      complications.

PMID- 30182772
TI  - Blood culture for complicated acute pyelonephritis with ureteral stone: are they
      unnecessary?

PMID- 30182773
TI  - Motivational interviewing in obese women with polycystic ovary syndrome - a pilot
      study.
AB  - Lifestyle intervention is first line treatment in obese women with polycystic
      ovary syndrome (PCOS). The effect of motivational interviewing (MI) as add on to
      standard advice (SA) on weight loss and quality of life (QoL) has not been
      evaluated in obese women with PCOS. We aimed to examine whether MI as add on to
      SA induced higher weight loss and improved QoL in obese women with PCOS. Thirty
      seven obese women with PCOS (BMI >=30 kg/m2) were randomized to MI + SA (n = 19)
      vs. SA (n = 18) for six months. Anthropometric measures (BMI, waist) and
      questionnaires (World Health Organization-5 (WHO-5), Major Depression Index
      (MDI), Short Form-36 (SF-36) and PCOS-Questionnaire (PCOS-Q)) were performed at
      baseline and at follow-up, www.clinicaltrials.gov, NCT02924025. Twenty-eight (14
      + 14) women completed the study. At baseline, 24/28 women had WHO-5 scores <67
      and 12/28 women had MDI scores indicating depression. Changes in weight and QoL
      were similar between MI + SA vs. SA group. However, WHO-5 (p=.028) and MDI
      (p=.008) scores improved significantly in the 12/24 women with MDI scores
      indicating depression. MI as add on to SA did not improve QoL or weight loss.
      Obese women with PCOS had low QoL.

PMID- 30182774
TI  - Inconclusive results in preimplantation genetic testing: go for a second biopsy?
AB  - The transition in biopsy timing from blastomere to trophectoderm biopsy has led
      to a remarkable decrease in the percentage of undiagnosed blastocysts. However,
      patients with few or no euploid blastocysts can be affected by this residual
      percentage of diagnosis failure. The aim of this study is to assess whether
      blastocyst rebiopsy and revitrification is an efficient and safe procedure to be
      applied in cases of no results after analysis. Fifty-three patients agreed to the
      warming of 61 blastocysts to perform a second biopsy and PGT-A by aCGH. Only
      75.4% of the blastocysts survived, reexpanded, and could be rebiopsied. After the
      second biopsy and analysis, 95.6% of the blastocysts were successfully diagnosed
      with an euploidy rate of 65.9%. Eighteen euploid blastocysts were warmed and
      transferred to 18 patients with a 100% survival and reexpansion rate. Seven
      clinical pregnancies have been achieved with 4 live births, 1 ongoing pregnancy,
      and 2 miscarriages. Thus, although few transfers of rebiopsied and revitrified
      blastocysts have been performed till date, our preliminary results show that this
      approach is efficient and safe to be applied for undiagnosed blastocysts, as it
      ultimately allows the transfer of euploid blastocysts and good clinical outcomes.

PMID- 30182775
TI  - Mechanism of long-term toxicity of CuO NPs to microalgae.
AB  - Little is known regarding the detailed mechanism of CuO NPs' toxicity to
      microalgal primary metabolism pathway. Photosynthesis and respiration are the
      most important primary metabolism and the main sources of production of reactive
      oxygen species (ROS), but the effect of CuO NPs on both of them has not been
      systematically studied to date. Our research demonstrated that long-term
      treatment with CuO NPs significantly inhibited activities of photosynthesis and
      respiration in microalgae, and the photosynthesis was more sensitive to the
      toxicity of CuO NPs than respiration. CuO NPs could be absorbed by microalgae and
      be converted into Cu2O NPs concentrated in chloroplast. The internalized Cu,
      regardless of whether the exposure was Cu2+ or CuO NPs had the same capacity to
      damage chloroplast structure. The result also shows that the oxygen-evolving
      complex (OEC) in the photosynthetic electron transport chain was the most
      sensitive site to CuO NPs and Cu2+-treated microalgae had the same damage site as
      that of CuO NPs, which may be related to the Mn cluster that is dissociated by Cu
      ions released from CuO NPs. The damage of OEC inhibited photosynthetic electron
      transport to increase excess excited energy, which caused the accumulation of ROS
      in chloroplast. The accumulation of ROS damaged the structure of cell membrane
      and aggravated the PSII photoinhibition, further decreasing the efficiency of
      light energy utilization. In conclusion, the Cu ionic toxicity of photosynthetic
      apparatus by CuO NPs resulted in the carbon starvation and the accumulation of
      ROS to inhibit the growth of microalgae.

PMID- 30182776
TI  - Grouping of nanomaterials to read-across hazard endpoints: a review.
AB  - The use of non-testing strategies like read-across in the hazard assessment of
      chemicals and nanomaterials (NMs) is deemed essential to perform the safety
      assessment of all NMs in due time and at lower costs. The identification of
      physicochemical (PC) properties affecting the hazard potential of NMs is crucial,
      as it could enable to predict impacts from similar NMs and outcomes of similar
      assays, reducing the need for experimental (and in particular animal) testing.
      This manuscript presents a review of approaches and available case studies on the
      grouping of NMs to read-across hazard endpoints. We include in this review
      grouping frameworks aimed at identifying hazard classes depending on PC
      properties, hazard classification modules in control banding (CB) approaches, and
      computational methods that can be used for grouping for read-across. The existing
      frameworks and case studies are systematically reported. Relevant nanospecific PC
      properties taken into account in the reviewed frameworks to support grouping are
      shape and surface properties (surface chemistry or reactivity) and hazard classes
      are identified on the basis of biopersistence, morphology, reactivity, and
      solubility.

PMID- 30182777
TI  - Abdominal wall endometriosis treatment by ultrasound-guided high-intensity
      focused ultrasound ablation: a case report.
AB  - Abdominal wall endometriosis (AWE) occurs in about 0.1% of people with
      endometriosis, and is often diagnosed postoperatively. Surgical resection is
      generally used to treat AWE. We successfully treated AWE with ultrasound-guided
      high-intensity focused ultrasound therapy (USgHIFU). A 37-year-old Korean female
      presented with a palpable subcutaneous nodule associated with cyclic pain and
      swelling during menstruation. She was recommended surgical excision three months
      ago. She had a history of laparoscopic surgery for endometriosis 4 years ago and
      was interested in less invasive methods of treatment. The 0.9 cm painful nodule
      was observed as a low-echoic shadow in transabdominal ultrasonography and as an
      iso-signal in T1 MRI images. USgHIFU treatment was performed under light sedation
      and completed when the hyperechoic area covered the entire lesion. HIFU treatment
      was effective without any postoperative complications such as blisters or skin
      burns. The lesion showed changes in hyper-intensity signal on T1 MRI images.
      Physical examination showed absence of pain or tenderness and three months later,
      the painful nodule shrunk, and the menstrual cyclic pain associated with the
      nodule disappeared. In conclusion, USgHIFU may represent an effective therapy for
      AWE.

PMID- 30182778
TI  - A nanoinformatics decision support tool for the virtual screening of gold
      nanoparticle cellular association using protein corona fingerprints.
AB  - The increasing use of nanoparticles (NPs) in a wide range of consumer and
      industrial applications has necessitated significant effort to address the
      challenge of characterizing and quantifying the underlying nanostructure -
      biological response relationships to ensure that these novel materials can be
      exploited responsibly and safely. Such efforts demand reliable experimental data
      not only in terms of the biological dose-response, but also regarding the
      physicochemical properties of the NPs and their interaction with the biological
      environment. The latter has not been extensively studied, as a large surface to
      bind biological macromolecules is a unique feature of NPs that is not relevant
      for chemicals or pharmaceuticals, and thus only limited data have been reported
      in the literature quantifying the protein corona formed when NPs interact with a
      biological medium and linking this with NP cellular association/uptake. In this
      work we report the development of a predictive model for the assessment of the
      biological response (cellular association, which can include both internalized
      NPs and those attached to the cell surface) of surface-modified gold NPs, based
      on their physicochemical properties and protein corona fingerprints, utilizing a
      dataset of 105 unique NPs. Cellular association was chosen as the end-point for
      the original experimental study due to its relevance to inflammatory responses,
      biodistribution, and toxicity in vivo. The validated predictive model is freely
      available online through the Enalos Cloud Platform (
      http://enalos.insilicotox.com/NanoProteinCorona/ ) to be used as part of a
      regulatory or NP safe-by-design decision support system. This online tool will
      allow the virtual screening of NPs, based on a list of the significant NP
      descriptors, identifying those NPs that would warrant further toxicity testing on
      the basis of predicted NP cellular association.

PMID- 30182780
TI  - Patients' perspectives of multidisciplinary home-based e-Health service delivery
      for motor neurone disease.
AB  - PURPOSE: To explore the views of people with motor neurone disease (MND) on the
      barriers, facilitators and potential benefits of using home-based e-Health
      service delivery (telehealth) to access MND multidisciplinary clinic care.
      METHODS: Twelve patients from three MND multidisciplinary clinics and an MND
      support association group completed a survey of information technology (IT) use
      and participated in interviews, to gather participants' experiences and
      perceptions of home-based telehealth for MND clinic care. Survey data were
      analyzed descriptively, with interview data analyzed using a stepwise inductive
      approach. RESULTS: Surveys revealed that participants used IT to communicate with
      family and friends, but were less likely to use the phone, email or
      videoconferencing with health professionals. Two themes of participants' use of
      IT in MND care reflected their experiences of MND care; and personal preferences
      for modes of healthcare delivery. Participants were willing to use telehealth for
      MND care, with family members acting as patients' main support for telehealth
      participation. Nevertheless, participants preferred face-to-face contact with the
      MND clinic team in the initial and early stages of the disease. CONCLUSIONS:
      People living with MND may wish to participate in individual care planning to
      facilitate their access to a variety of e-Health service modalities.
      Additionally, individual care planning may allow healthcare professionals to
      deliver e-Health-based care, such as telehealth, to increase the scope of care
      provided. Research to ascertain the views of health professionals and family
      members as co-participants in service delivery via telehealth is needed to fully
      assess the potential contribution of e-Health. Implications for Rehabilitation
      People living with MND face a range of barriers to attending specialized
      multidisciplinary care, including fatigue, caregiver availability and logistical
      challenges to travel. Patients have indicated willingness to use e-Health
      applications to improve their access to care. Use of telehealth could expand
      service delivery to people with MND living long distances from multidisciplinary
      clinics, and increase the patient-centred focus of care by tailoring care
      planning. By offering telehealth services routinely, MND multidisciplinary
      clinics could also improve the quality and timelines of services offered.

PMID- 30182781
TI  - Postpartum assessment of the beta cell function and insulin resistance for
      Chinese women with previous gestational diabetes mellitus.
AB  - Gestational diabetes mellitus (GDM) imparts a high risk of developing postpartum
      diabetes and is considered to be an early stage of type 2 diabetes mellitus
      (T2DM). In this study, a 75-g oral glucose tolerance test was performed on 472
      women with GDM at 6-8 weeks after delivery. The clinical and metabolic
      characteristics were compared between the patients with normal glucose tolerance
      (NGT) and abnormal glucose metabolism (AGM). These data were then compared
      between pre-diabetic and diabetic patients. A total of 37.7% of the women with
      GDM continued to have abnormal glucose levels after delivery. Compared with the
      women who reverted to normal, HOMA-IR was significantly higher in AGM. A multiple
      stepwise regression analysis revealed that age, the postpartum body mass index
      (BMI), low density lipoprotein-cholesterol (LDL-C), 2 h glucose load plasma
      glucose (2 h PG), triglycerides (TG), hemoglobin A1c (HbA1c), 1 h glucose load
      plasma insulin (INS) level, and 2 h INS level were independent risk factors for
      the development of insulin resistance after delivery. This study has identified a
      high prevalence of AGM after GDM. Insulin resistance appears to be the major
      contributor. Any treatment to reduce the postpartum BMI and lipids level may be
      beneficial to decrease insulin resistance.

PMID- 30182782
TI  - Dual Burdens of Care: "Sandwiched Couples" in East Asia.
AB  - OBJECTIVE: To estimate proportions of married couples aged 30 to 59 years who
      face simultaneous demands from elderly parents and children in China, Japan,
      Korea, and Taiwan, and the effects on couples' life and marital satisfaction.
      METHOD: Using data from the 2006 East Asian Social Survey, proportions of
      sandwiched couples were estimated using three definitions: co-residence, co
      residence or nearby residence, and co-residence or frequent provision of
      financial/physical assistance. Logistic regression models were used to assess the
      effects on life and marital satisfaction. RESULTS: Three-generational co
      residence is more common in Taiwan and Japan (24.3% and 21.4%), whereas co
      residence or provision for both generations is higher in Taiwan and Korea (53.7%
      and 44.5%). The strain of being sandwiched is associated with lower life and
      marital satisfaction only among women. DISCUSSION: Intergenerational transfers of
      care play a major role in elderly support in East Asia but take a toll on the
      well-being of married women.

PMID- 30182779
TI  - Genetic susceptibility to cerebrovascular disease: A systematic review.
AB  - Investigation of genetic susceptibility to cerebrovascular disease has been of
      growing interest. A systematic review of human studies assessing neurogenomic
      aspects of cerebrovascular disease was performed according to the preferred
      reporting items for systematic reviews and meta-analyses (PRISMA) statement. Any
      association study exploring genetic variants located in the exome associated with
      one of the major cerebrovascular diseases with at least 500 subjects was eligible
      for inclusion. Of 6874 manuscripts identified, 35 studies met the inclusion
      criteria. Most studies of interest focused on ischemic stroke and cerebrovascular
      occlusive disease. Large cohort genetic association studies on hemorrhagic
      cerebrovascular disease were less common. In addition to rare, well-established
      monogenic conditions with significant risk for cerebrovascular disease, a number
      of genetic variants are also relevant to cerebrovascular pathogenesis as part of
      a multifactorial process. The 45 polymorphisms identified were located in genes
      involved in processes related to endothelial and vascular health (15 (33.4%)
      variants), plasma lipid metabolism (10 (22.2%) variants), inflammation (9 (20%)
      variants), coagulation (3 (6.7%) variants), and blood pressure modulation (2
      (4.4%) variants), and other (6 (13.3%) variants). This work represents a
      comprehensive overview of genetic variants in the exome relevant to ischemic and
      hemorrhagic stroke pathophysiology.

PMID- 30182783
TI  - Differential effects of clomipramine on depression-like behaviors induced by the
      chronic social defeat paradigm in tree shrews.
AB  - BACKGROUND: Anhedonia is a hallmark symptom in major depression that reflects
      deficits in hedonic capacity and it is also linked to motivation for reward.
      However, studies of the features of motivation in depressed tree shrews are
      rather sparse. AIMS: The study aimed to investigate the core feature of
      depression including lack of interest, motivation reduction, and social avoidance
      in tree shrews. Furthermore, the effects of the treatment using clomipramine on
      these depression-like behaviors were assessed. METHODS: The paradigm of chronic
      social defeat in tree shrews was used to evaluate the core feature of depression
      through examining their sucrose preference, break-point for reward, and social
      interaction. RESULTS: The results showed that social defeat lowered the curves of
      the sucrose preference and the break-point, as well as decreased social
      interaction. The results suggested that the subordinate animals exhibited
      interest loss, motivational reduction, and social avoidance. After oral treatment
      with clomipramine (50 mg/kg/day) for four weeks, most of the depression-like
      behaviors were reversed, whereas the motivational reduction was not clearly
      affected. Notably, the motivational reduction appeared obviously during the first
      week after the social defeat, and the conventional tricyclic antidepressant
      clomipramine did not reverse the reduced motivation. CONCLUSIONS: These findings
      imply that motivational variation might be applied as a more sensitive behavioral
      index in subordinate animals and could furthermore be used to evaluate potential
      agents as antidepressants.

PMID- 30182784
TI  - Preclinical hazard evaluation strategy for nanomedicines.
AB  - The increasing nanomedicine usage has raised concerns about their possible impact
      on human health. Present evaluation strategies for nanomaterials rely on a case
      by-case hazard assessment. They take into account material properties, biological
      interactions, and toxicological responses. Authorities have also emphasized that
      exposure route and intended use should be considered in the safety assessment of
      nanotherapeutics. In contrast to an individual assessment of nanomaterial
      hazards, we propose in the present work a novel and unique evaluation strategy
      designed to uncover potential adverse effects of such materials. We specifically
      focus on spherical engineered nanoparticles used as parenterally administered
      nanomedicines. Standardized assay protocols from the US Nanotechnology
      Characterization Laboratory as well as the EU Nanomedicine Characterisation
      Laboratory can be used for experimental data generation. We focus on both
      cellular uptake and intracellular persistence as main indicators for nanoparticle
      hazard potentials. Based on existing regulatory specifications defined by
      authorities such as the European Medicines Agency and the United States Food and
      Drug Administration, we provide a robust framework for application-oriented
      classification paired with intuitive decision making. The Hazard Evaluation
      Strategy (HES) for injectable nanoparticles is a three-tiered concept covering
      physicochemical characterization, nanoparticle (bio)interactions, and hazard
      assessment. It is cost-effective and can assist in the design and optimization of
      nanoparticles intended for therapeutic use. Furthermore, this concept is designed
      to be adaptable for alternative exposure and application scenarios. To the
      knowledge of the authors, the HES is unique in its methodology based on exclusion
      criteria. It is the first hazard evaluation strategy designed for
      nanotherapeutics.

PMID- 30182785
TI  - Increasing spatial resolution of photoregulated GTPases through immobilized
      peripheral membrane proteins.
AB  - Light-induced dimerizing systems, e.g. iLID, are an increasingly utilized
      optogenetics tool to perturb cellular signaling. The major benefit of this
      technique is that it allows external spatiotemporal control over protein
      localization with sub-cellular specificity. However, when it comes to local
      recruitment of signaling components to the plasmamembrane, this precision in
      localization is easily lost due to rapid diffusion of the membrane anchor. In
      this study, we explore different approaches of countering the diffusion of
      peripheral membrane anchors, to the point where we detect immobilized fractions
      with iFRAP on a timescale of several minutes. One method involves simultaneous
      binding of the membrane anchor to a secondary structure, the microtubules. The
      other strategy utilizes clustering of the anchor into large immobile structures,
      which can also be interlinked by employing tandem recruitable domains. For both
      approaches, the anchors are peripheral membrane constructs, which also makes them
      suitable for in vitro use. Upon combining these slower diffusing anchors with
      recruitable guanine exchange factors (GEFs), we show that we can elicit much more
      localized morphological responses from Rac1 and Cdc42 as compared to a regular
      CAAX-box based membrane anchor in living cells. Thanks to these new slow
      diffusing anchors, more precisely defined membrane recruitment experiments are
      now possible.

PMID- 30182786
TI  - Multiple daytime administration of the selective orexin-2 receptor antagonist JNJ
      42847922 induces somnolence in healthy subjects without residual central effects.
AB  - BACKGROUND:: Pharmacokinetics, pharmacodynamics and general safety and
      tolerability of JNJ-42847922, a selective orexin-2 receptor antagonist, were
      assessed in healthy subjects. METHODS:: Five consecutive cohorts of healthy
      subjects were enrolled and received doses of 5-60 mg orally once daily over 10
      days of JNJ-42847922 ( n=6) or placebo ( n=2). Concentrations of drug in plasma
      and urine were measured over 24 h after dosing on Days 1, 5 and 10. Observed- and
      self-reported somnolence was used to evaluate the principal pharmacodynamic
      effect of JNJ-42847922. A test battery to assess vigilance state, sedation and
      alertness was assessed at 4, 6 and 8 h after dosing. Safety assessments included
      recording of adverse events, vital signs, electrocardiograms, clinical laboratory
      assessments and suicidality per Columbia Suicide Severity Rating Scale. RESULTS::
      JNJ-42847922 was rapidly absorbed after the morning dose administration. The
      median tmax ranged from 0.5-1.5 h and mean t1/2 values from 2-3 h. At JNJ
      42847922 dose levels ?20 mg, mean Cmax and mean area under the curve, values
      increased less than dose proportionally. At doses ?20 mg, JNJ-42847922
      consistently induced somnolence on all study days. At four hours post-dose
      administration, dose levels >5 mg JNJ-42847922 were identified as sedating by the
      Addiction Research Center Inventory-49. Except for a mild decrease in attention
      (Bond and Lader Visual Analogue Scale Factor 1) at dose levels >10 mg at four
      hours post-dose, no clinically relevant changes in other central measures have
      been observed. JNJ-42847922 was well tolerated.

PMID- 30182787
TI  - Rapid antidepressant effects of deep brain stimulation of the pre-frontal cortex
      in an animal model of treatment-resistant depression.
AB  - BACKGROUND: A significant proportion of depressed patients fail to respond to
      treatment with antidepressant drugs. Such patients might nonetheless respond to
      deep brain stimulation of the prefrontal cortex. Deep brain stimulation has also
      been shown to normalize behaviour in the chronic mild stress (CMS) model of
      depression. However, these studies have involved animals that are in general
      treatment responsive. Thus, this is not the ideal situation in which to
      investigate how deep brain stimulation is effective where antidepressant drugs
      are not. AIMS: Here, we studied the behavioural effects of deep brain stimulation
      in treatment-resistant animals. METHODS: Wistar rats were exposed to chronic mild
      stress and concurrent treatment with saline or one of three antidepressant drugs,
      imipramine, citalopram and venlafaxine. Individuals were selected from the CMS
      exposed drug-treated groups that had failed to increase their sucrose intake by
      week 5 of drug treatment. All animals were then implanted with deep brain
      stimulation electrodes in the ventro-medial prefrontal cortex, and tested for
      sucrose intake and in the elevated plus maze and novel object recognition test,
      following 2 * 2 h of deep brain stimulation. RESULTS: The selected drug-treated
      animals were found to be antidepressant-resistant in all three tests. With a
      single exception (sucrose intake in imipramine-treated animals), deep brain
      stimulation reversed the anhedonic, anxiogenic and dyscognitive effects of CMS in
      all four conditions, with no significant differences between saline- and drug
      treated animals. CONCLUSIONS: These data provide a proof of principle that deep
      brain stimulation of the prefrontal cortex can be effective in a rat model of
      resistance to chronic antidepressant treatment, replicating the clinical effect
      of deep brain stimulation in treatment-resistant depression.

PMID- 30182789
TI  - Erratum.

PMID- 30182788
TI  - Hypercapnia increases brain viscoelasticity.
AB  - Brain function, the brain's metabolic activity, cerebral blood flow (CBF), and
      intracranial pressure are intimately linked within the tightly autoregulated
      regime of intracranial physiology in which the role of tissue viscoelasticity
      remains elusive. We applied multifrequency magnetic resonance elastography (MRE)
      paired with CBF measurements in 14 healthy subjects exposed to 5-min carbon
      dioxide-enriched breathing air to induce cerebral vasodilatation by hypercapnia.
      Stiffness and viscosity as quantified by the magnitude and phase angle of the
      complex shear modulus, | G*| and phi, as well as CBF of the whole brain and 25
      gray matter sub-regions were analyzed prior to, during, and after hypercapnia. In
      all subjects, whole-brain stiffness and viscosity increased due to hypercapnia by
      3.3 +/- 1.9% and 2.0 +/- 1.1% which was accompanied by a CBF increase of 36 +/-
      15%. Post-hypercapnia, | G*| and phi reduced to normal values while CBF decreased
      by 13 +/- 15% below baseline. Hypercapnia-induced viscosity changes correlated
      with CBF changes, whereas stiffness changes did not. The MRE-measured viscosity
      changes correlated with blood viscosity changes predicted by the Fahraeus
      Lindqvist model and microvessel diameter changes from the literature. Our results
      suggest that brain viscoelastic properties are influenced by microvessel blood
      flow and blood viscosity: vasodilatation and increased blood viscosity due to
      hypercapnia result in an increase in MRE values related to viscosity.

PMID- 30182790
TI  - Reply to Letter to the Editor: Choroidal Thickness in Diabetic Macular Edema
      Compared to Normal Controls.

PMID- 30182791
TI  - Leveraging Data to Strengthen Campus Sexual Assault Policies.
AB  - The U.S. Department of Education recently announced that existing legislation and
      guidance on campus sexual assault (CSA) policies had created a "failed system" in
      institutions of higher education. This announcement raises the question of how
      CSA legislation and guidance should be evaluated and applied in practice. We
      believe researchers are well situated to not only leverage data and empirically
      evaluate the success (or failure) of CSA federal and university policies but also
      to facilitate development of improved, more effective CSA policy. This commentary
      first chronicles the pivotal role of federal policy and guidance in driving the
      collection of CSA data and increasing research efforts in this domain. Second, we
      present recommendations for increased collaboration among researchers,
      practitioners, and policy makers aimed at measuring the effectiveness of current
      CSA policies and promoting data-driven policy. These recommendations focus on (a)
      establishing a CSA data repository, (b) analyzing existing CSA data to gain
      knowledge and identify opportunities for improved data collection, and

PMID- 30182792
TI  - Reduced acquisition time PET pharmacokinetic modelling using simultaneous ASL
      MRI: proof of concept.
AB  - Pharmacokinetic modelling on dynamic positron emission tomography (PET) data is a
      quantitative technique. However, the long acquisition time is prohibitive for
      routine clinical use. Instead, the semi-quantitative standardised uptake value
      ratio (SUVR) from a shorter static acquisition is used, despite its sensitivity
      to blood flow confounding longitudinal analysis. A method has been proposed to
      reduce the dynamic acquisition time for quantification by incorporating cerebral
      blood flow (CBF) information from arterial spin labelling (ASL) magnetic
      resonance imaging (MRI) into the pharmacokinetic modelling. In this work, we
      optimise and validate this framework for a study of ageing and preclinical
      Alzheimer's disease. This methodology adapts the simplified reference tissue
      model (SRTM) for a reduced acquisition time (RT-SRTM) and is applied to [18F]
      florbetapir PET data for amyloid-beta quantification. Evaluation shows that the
      optimised RT-SRTM can achieve amyloid burden estimation from a 30-min PET/MR
      acquisition which is comparable with the gold standard SRTM applied to 60 min of
      PET data. Conversely, SUVR showed a significantly higher error and bias, and a
      statistically significant correlation with tracer delivery due to the influence
      of blood flow. The optimised RT-SRTM produced amyloid burden estimates which were
      uncorrelated with tracer delivery indicating its suitability for longitudinal
      studies.

PMID- 30182793
TI  - Age, Perceptions of Mattering, and Allostatic Load.
AB  - OBJECTIVES: Engagement in close personal ties has been shown to reduce risk for
      morbidity and mortality. In this study, we assess the extent to which one
      dimension of social relationships, mattering to others, conditions the positive
      relationship between age and allostatic load (AL). We do so to test the
      assumption that age-related declines in health are less prominent among those
      with high levels of mattering. METHOD: Poisson regression models were estimated
      using data from the Nashville Stress and Health Study (NSAHS). The NSAHS is a
      community-based study of 1,026 African American and White study participants,
      aged 22 to 69 years, residing in Davidson County, Tennessee. RESULTS: Analyses
      revealed that mattering conditioned or modified the relationship between age and
      AL. Specifically, we found that AL increases with age and this increase was
      significantly greater among those with moderate or low perceptions of mattering
      to others. DISCUSSION: This study confirms that perceptions of mattering to one's
      significant others are inversely related to physical health problems. This is so
      because mattering captures the positive and protective aspects of these
      relationships.

PMID- 30182794
TI  - The Early Use of Vacuum Therapy for Penile Rehabilitation After Radical
      Prostatectomy: Systematic Review and Meta-Analysis.
AB  - Vacuum therapy has been widely used for penile rehabilitation after radical
      prostatectomy (RP), but its efficacy and safety are unclear. The study was to
      evaluate the efficacy and safety of the early use of vacuum therapy for post-RP
      men. Randomized clinical trials were selected according to predefined inclusion
      and exclusion criteria. RevMan 5.3 software was used for meta-analyses. In total,
      six randomized controlled trials were included with a total of 273 post-RP
      patients. The meta-analysis revealed that the early use of vacuum therapy could
      significantly improve the five-item International Index of Erectile Function and
      penile shrinkage in post-RP patients. Few adverse events were reported across the
      included studies. This review suggests that the early use of vacuum therapy
      appears to have excellent therapeutic effect on post-RP patients and no serious
      side effects were identified. Due to overall limited quality of the included
      studies, the therapeutic benefit of vacuum therapy in penile rehabilitation needs
      be substantiated to a limited degree in the future. Better methodological, large
      controlled trials are expected to verify the therapeutic effect of vacuum therapy
      in penile rehabilitation.

PMID- 30182795
TI  - Does getting high hurt? Characterization of cases of LSD and psilocybin
      containing mushroom exposures to national poison centers between 2000 and 2016.
AB  - BACKGROUND:: Lysergic acid diethylamide (LSD) and psilocybin are serotonergic
      hallucinogens that are used primarily for recreational abuse. Small studies
      evaluated the efficacy of LSD and psilocybin for several psychiatric conditions.
      There are limited safety or toxicity data for either of these substances,
      especially in large populations. METHODS:: This was a retrospective analysis of
      single-substance exposures of LSD or psilocybin-containing mushrooms (PcMs)
      reported to United States poison centers from 1 January 2000 to 31 December 2016.
      The study describes the most frequent toxicities, management sites, and medical
      outcomes. RESULTS:: A total of 5883 PcM and 3554 LSD exposures were included.
      Most patients were between 13 and 29 years of age (83.9% PcM, 88.9% LSD) and
      primarily male (77.9% PcM, 74.1% LSD). Most common clinical effects were
      hallucinations (45.8% PcM, 37.4% LSD), agitation (24.1% PcM, 42.4% LSD), and
      tachycardia (18.0% PcM, 38.6% LSD). Serious clinical effects were infrequent, but
      included hyperthermia, seizures, coma, increased serum creatinine, and cardiac
      arrest. Most patients were treated and released from the emergency department.
      More LSD patients were admitted to critical care and non-critical care units than
      PcM patients. Moderate effect was the most frequent outcome for both substances
      (61.0% PcM, 62.3% LSD). CONCLUSION:: These data find that LSD and PcM use occurs
      primarily in adolescents and young adults, who experience mild to moderate
      adverse effects. Serious effects are infrequent but can occur. While most LSD and
      PcM users require only emergency department management, LSD use is more likely to
      require medical admission.

PMID- 30182796
TI  - Tubular vesicopyelostomy for the management of types 2 and 3 (long-segment)
      ureteric stenosis after kidney transplantation.
AB  - Late ureteral stenosis following kidney transplantation needs immediate
      correction in order to protect allograft function and requires a complicated
      surgical procedure. In this study, we present the long-term results of tubular
      bladder reconfiguration and cystopyelostomy (tubular vesicopyelostomy), an
      innovative and practical procedure for the management of long-segment ureteric
      stenosis (types 2 and 3) after transplantation. Between 2002 and 2017, 722 kidney
      transplant patients were monitored at the University of Medical Sciences, Bozyaka
      Organ Transplantation and Research Center. Twenty-eight of these patients
      underwent tubular vesicopyelostomy operation; 17 male and 11 female patients with
      a mean age of 45.6 +/- 10.5 years. Time to surgical intervention for urinary
      tract obstruction was 122.5 +/- 114.7 months. The mean serum creatinine values
      previous to and 3 days following the tubular vesicopyelostomy operation were 3.46
      +/- 1.5 mg/dL and 1.75 +/- 0.7 mg/dL, respectively (p < 0.0001). Within a mean
      follow-up period of 55.1 +/- 40.9 months, functional grafts were recorded in 22
      patients with a mean serum creatinine value of 1.92 +/- 0.8 mg/dL. Only one
      patient developed anastomotic stenosis after the tubular vesicopyelostomy
      procedure, giving an overall success rate for tubular vesicopyelostomy of 96.4%.
      Six patients returned to hemodialysis. In five, the underlying etiology was not
      related to recurrent obstruction or surgical complications. Sixteen patients
      underwent allograft biopsy after the operation, but features of
      tubulointerstitial nephritis were seen in only one. Tubular vesicopyelostomy
      operation is a safe and successful method for the surgical treatment of late and
      complicated ureteral obstructions with excellent long-term results. It may be a
      good, practical alternative to other more sophisticated surgical options.

PMID- 30182797
TI  - Rapid effectiveness of intravenous ketamine for ultraresistant depression in a
      clinical setting and evidence for baseline anhedonia and bipolarity as clinical
      predictors of effectiveness.
AB  - BACKGROUND: Intravenous ketamine has been established as an efficacious and safe
      treatment, with transient effect, for treatment-resistant depression. However,
      the effectiveness of intravenous ketamine in non-research settings and with
      ultraresistant depression patients remains understudied. AIMS: This study aims to
      measure the response and remission rates in ultraresistant depression patients in
      a clinical setting by means of a retrospective, open label, database study.
      Secondarily, the study will attempt to support previous findings of clinical
      predictors of effectiveness with intravenous ketamine treatment. METHODS: Fifty
      patients with ultraresistant depression were treated between May 2015-December
      2016, inclusive, in two community hospitals in Edmonton using six ketamine
      infusions of 0.5 mg/kg over 40 min over 2-3 weeks. Data were collected
      retrospectively from inpatient and outpatient charts. Statistical analysis to
      investigate clinical predictors of effectiveness included logistic regression
      analysis using a dependent variable of a 50% reduction in rating scale score at
      any point during treatment. RESULTS: At baseline, the average treatment
      resistance was severe, with a Maudsley Staging Method score of 12.1 out of 15,
      90.0% were resistant to electroconvulsive therapy, and the average Beck
      Depression Inventory score was 34.2. The response rate was 44% and remission rate
      was 16%. As a single predictor, moderate or severe anhedonia at baseline
      predicted a 55% increased likelihood of response. As a combined predictor, this
      level of anhedonia at baseline with a diagnosis of bipolar depression predicted a
      73% increase in likelihood of response. CONCLUSION: In a clinical setting,
      intravenous ketamine showed effectiveness in a complex, severely treatment
      resistant, depressed population on multiple medication profiles concurrently.
      This study gave support to anhedonia and bipolar depression as clinical
      predictors of effectiveness.

PMID- 30182798
TI  - Functional Ability, Participation, and Health-Related Quality of Life After Hip
      Fracture.
AB  - Hip fracture is prevalent among older adults impacting on all aspects of daily
      life. The gaols of this study were: (a) Examine the trajectory of activities of
      daily living (ADL)/instrumental activities of daily living (IADL) functioning and
      participation among older adults with hip fracture from prefracture to 6-months
      postrehabilitation; (b) determine the relationship between health-related quality
      of life (HRQoL), functional abilities, and participation 6-months
      postrehabilitation; and (c) examine whether functional outcomes can predict
      HRQoL. Both retrospective and prospective data were analyzed. Fifty-five
      participants (Mean age = 80.82) completed the motor component of the functional
      independence measure (mFIM), IADL questionnaire, Activity Card Sort, and SF-12.
      Prefracture levels of function and participation were not attained. Significant
      correlations were found between HRQoL, functional abilities, and participation.
      ADL functioning and mobility predicted Physical SF-12, whereas social-cultural
      activity predicted Mental SF-12. Significant loss of functioning and
      participation was found, persisting 6 months after rehabilitation that impede
      their HRQoL. Improving functioning, mobility, and social participation can be
      achieved by occupational therapy intervention for promoting HRQoL among elderly
      with hip fracture.

PMID- 30182799
TI  - From Molecules to Mechanisms: Functional Proteomics and Its Application to Renal
      Tubule Physiology.
AB  - Classical physiological studies using electrophysiological, biophysical,
      biochemical, and molecular techniques have created a detailed picture of
      molecular transport, bioenergetics, contractility and movement, and growth, as
      well as the regulation of these processes by external stimuli in cells and
      organisms. Newer systems biology approaches are beginning to provide deeper and
      broader understanding of these complex biological processes and their dynamic
      responses to a variety of environmental cues. In the past decade, advances in
      mass spectrometry-based proteomic technologies have provided invaluable tools to
      further elucidate these complex cellular processes, thereby confirming,
      complementing, and advancing common views of physiology. As one notable example,
      the application of proteomics to study the regulation of kidney function has
      yielded novel insights into the chemical and physical processes that tightly
      control body fluids, electrolytes, and metabolites to provide optimal
      microenvironments for various cellular and organ functions. Here, we
      systematically review, summarize, and discuss the most significant key findings
      from functional proteomic studies in renal epithelial physiology. We also
      identify further improvements in technological and bioinformatics methods that
      will be essential to advance precision medicine in nephrology.

PMID- 30182800
TI  - Resting regional brain activity and connectivity vary with resting blood pressure
      but not muscle sympathetic nerve activity in normotensive humans: An exploratory
      study.
AB  - Blood pressure is tightly controlled by the central nervous system, particularly
      the brainstem. The aim of this study was to investigate the relationship between
      mean blood pressure (MBP), muscle sympathetic nerve activity (MSNA) and resting
      regional brain activity in healthy human subjects. Pseudocontinuous arterial spin
      labeling and functional magnetic resonance imaging of the brain were performed
      immediately following a laboratory microneurography recording of MSNA and BP
      measurement in 31 young, healthy normotensive subjects. Regional cerebral blood
      flow (CBF) correlated significantly with resting MBP levels in the region
      encompassing the rostroventrolateral medulla (RVLM), dorsolateral pons, and
      insular, prefrontal and cingulate cortices. Functional connectivity analysis
      revealed that the ventrolateral prefrontal cortex displayed greater resting
      connectivity strength within the RVLM in the lower compared with the higher MBP
      group. No significant differences in CBF were found when subjects were divided
      based on their MSNA levels. These results suggest that even subtle differences in
      resting MBP are associated with significant differences in resting activity in
      brain regions, which are well known to play a role in cardiovascular function.
      These data raise the question of the potential long-term consequences of
      differences in regional brain activity levels and their relationship with
      systemic blood pressure.

PMID- 30182801
TI  - Evolution of Brain Glucose Metabolic Abnormalities in Children With Epilepsy and
      SCN1A Gene Variants.
AB  - Three children with drug-refractory epilepsy, normal magnetic resonance image
      (MRI), and a heterozygous SCN1A variant underwent 2-deoxy-2-[18F]fluoro-d-glucose
      positron emission tomography (FDG-PET) scanning between age 6 months and 1 year
      and then at age 3 years 6 months to 5 years 5 months. Regional FDG uptake values
      were compared to those measured in age- and gender-matched pseudo-controls. At
      baseline, the brain glucose metabolic pattern in the SCN1A group was similar to
      that of the pseudo-controls. At follow-up, robust decreases of normalized FDG
      uptake was found in bilateral frontal, parietal and temporal cortex, with milder
      decreases in occipital cortex. Children with epilepsy and an SCN1A variant have a
      normal pattern of cerebral glucose metabolism at around 1 year of age but develop
      bilateral cortical glucose hypometabolism by age 4 years, with maximal decreases
      in frontal, parietal, and temporal cortex. This metabolic pattern may be
      characteristic of epilepsy associated with SCN1A variants and may serve as a
      biomarker to monitor disease progression and response to treatments.

PMID- 30182802
TI  - Sociocultural Aspects of Femicide-Suicide: The Case of Israel.
AB  - Among persons who commit murder a certain percentage also commits suicide soon
      after, a phenomenon known as homicide-suicide. Previous studies indicate that
      femicide-suicide (female intimate partner homicide-suicides) accounts for the
      vast majority of homicide-suicide occurrences. Although the femicide-suicide
      phenomenon cuts across regions and societies, there is a dearth of studies of
      femicide-suicide patterns, motives, and characteristics among non-Western
      populations. A review of the few available findings about femicide-suicide in non
      Western societies highlights the need for further study and corroboration of the
      distribution and characteristics of femicide-suicide in non-Western societies.
      The unique manifestations of the phenomenon among immigrant, ethnic, and social
      minority groups are of great relevance to Western societies currently facing the
      challenge of assimilating a growing number of ethnic minorities and immigrant
      social groups. The study aims to further our understanding of possible
      sociocultural variations of femicide-suicide by exploring sociodemographic and
      criminological patterns among non-Western social groups. It presents an analysis
      of national empirical findings of femicide-suicide across various ethnic and
      sociocultural groups in Israel in the years 2005-2015, excluding analysis of
      cases that occurred in Gaza, the West Bank, and East Jerusalem. The
      characteristics and patterns that are the focus of this study include a
      sociocultural ethnic profile of the perpetrator, and various criminological
      characteristics such as homicide and suicide location, homicide and suicide
      method, and homicide motive. Femicide-suicide events, victims, and perpetrators
      were compared by calculating frequency distributions and population-based
      incidence rates. The findings suggest that the distribution of the phenomenon and
      its criminological characteristics vary across immigrant and ethnic minority
      groups. Further research is needed to validate the study's empirical observations
      and to explore the various manifestations of the phenomenon across non-Western
      ethnic, social, religious, and cultural groups.

PMID- 30182803
TI  - Centralizing Temporality in Adolescent and Young Adult Cancer Survivorship.
AB  - Drawing on Gadamer's hermeneutic philosophy, this article presents a key outcome
      of broader research into the phenomenon of adolescent and young adult cancer
      survivorship. Data were generated through semi-structured interviews with 45
      participants from Australia, England, and the United States. The participants
      received a cancer diagnosis between the ages of 15 and 29 years and were aged 18
      to 40 years at the time of interview. The key analytical finding depicts the
      concept of time as central to the experiences in survivorship. Altered beliefs in
      temporal progression and biographical chronology affected the organization of
      time, the structuring and value of life events, and the use of time as a
      resource. The significance of temporality in young survivors' experiences
      warrants its centrality in the design of survivorship care models that reflect a
      broader understanding of the life experiences of this population.

PMID- 30182804
TI  - Guidelines for the Evaluation and Treatment of Perimenopausal Depression: Summary
      and Recommendations.
AB  - There is a new appreciation of the perimenopause-defined as the early and late
      menopause transition stages as well as the early postmenopause-as a window of
      vulnerability for the development of both depressive symptoms and major
      depressive episodes. However, clinical recommendations on how to identify,
      characterize and treat clinical depression are lacking. To address this gap, an
      expert panel was convened to systematically review the published literature and
      develop guidelines on the evaluation and management of perimenopausal depression.
      The areas addressed included: (1) epidemiology; (2) clinical presentation; (3)
      therapeutic effects of antidepressants; (4) effects of hormone therapy; and (5)
      efficacy of other therapies (e.g., psychotherapy, exercise, and natural health
      products). Overall, evidence generally suggests that most midlife women who
      experience a major depressive episode during the perimenopause have experienced a
      prior episode of depression. Midlife depression presents with classic depressive
      symptoms commonly in combination with menopause symptoms (i.e., vasomotor
      symptoms, sleep disturbance), and psychosocial challenges. Menopause symptoms
      complicate, co-occur, and overlap with the presentation of depression. Diagnosis
      involves identification of menopausal stage, assessment of co-occurring
      psychiatric and menopause symptoms, appreciation of the psychosocial factors
      common in midlife, differential diagnoses, and the use of validated screening
      instruments. Proven therapeutic options for depression (i.e., antidepressants,
      psychotherapy) are the front-line treatments for perimenopausal depression.
      Although estrogen therapy is not approved to treat perimenopausal depression,
      there is evidence that it has antidepressant effects in perimenopausal women,
      particularly those with concomitant vasomotor symptoms. Data on estrogen plus
      progestin are sparse and inconclusive.

PMID- 30182805
TI  - On the relation between dimensions of fatigue and depression in adolescents and
      young adults with acquired brain injury.
AB  - Complaints of fatigue following acquired brain injury (ABI) are often associated
      with depression. However, the nature of this relationship is unclear;
      furthermore, research among young people with ABI is limited. The objective of
      this cross-sectional study was (1) to investigate levels of depression in young
      outpatients with ABI (15-30 years old) and (2) to determine how different
      dimensions of fatigue relate to depression. Five dimensions of fatigue were
      assessed with the Multidimensional Fatigue Inventory (MFI-20), and depression was
      assessed with the Major Depression Inventory (MDI). Mann-Whitney U-tests and
      multiple regression analyses were conducted. The ABI group (n = 105), on average
      23.7 years old (SD = 4.2) and 31 months post-injury (SD = 61), had elevated
      levels of fatigue and depression compared to a convenience sample of 160 healthy
      controls, all p's < .001. In multivariate analyses, the predominantly mental
      dimensions of fatigue, General Fatigue, Mental Fatigue, and Reduced Motivation,
      were independently associated with MDI, all p's < .01, while the physical
      dimensions, Physical Fatigue and Reduced Activity, were not. Distinctions within
      the concept of fatigue may be important in relation to depression, and future
      research could benefit from adopting a multidimensional approach in the
      development of more targeted and effective treatments of fatigue and depression
      following ABI.

PMID- 30182806
TI  - Consequences on economic outcomes of generic versus brand-name drugs used in
      routine clinical practice: the case of treating peripheral neuropathic pain or
      generalized anxiety disorder with pregabalin.
AB  - BACKGROUND: Discrepancies are seen between arguments in favor of and against
      prescribing generic versus brand-name drugs. OBJECTIVE: To provide real-world
      evidence on treatment persistence, economic and clinical outcomes of pregabalin,
      generic versus brand-name (Lyrica(r), Pfizer), routinely used to treat
      neuropathic pain (NP) or generalized anxiety disorder (GAD). METHODS: Electronic
      medical records from subjects' first starting treatment with pregabalin between
      January-2015 and June-2016 were analyzed. Persistence, resources utilization, and
      costs were assessed, along with remitter and responder rates. RESULTS: A total of
      4860 records were analyzed. Discontinuation was lower with brand-name than with
      generic in NP (adjusted hazard ratio [HR]: 0.70 [95% CI: 0.58-0.85], p < 0.001)
      and GAD patients (HR: 0.63 [0.45-0.84], p < 0.001). Adjusted mean total costs
      were lower with brand-name: ?1500 [1428-1573] vs. ?2003 [1864-2143] in NP and
      ?1528 [1322-1734] vs. ?2150 [1845-2454] in GAD (both p < 0.001). More patients
      were remitters/ responders with brand-name in NP (55.0% vs. 46.7% and 59.2% vs.
      48.4%, respectively; p < 0.001) and GAD (58.6% vs. 48.7% and 64.6% vs. 47.2%,
      respectively; p < 0.001). CONCLUSIONS: As a consequence of higher persistence in
      routine practice, patients who first started therapy with pregabalin brand-name
      versus generic showed better pain or anxiety outcomes at a lower cost to payers
      in Spain.

PMID- 30182807
TI  - Comparison of in vivo remodeling of urinary bladder matrix and acellular dermal
      matrix in an ovine model.
AB  - AIM: Biologically derived surgical graft materials come from a variety of sources
      with varying mechanical properties. This study aimed to evaluate the host
      response and mechanical performance of two extracellular matrix devices in a
      large animal preclinical model. MATERIALS & METHODS: Bilateral defects were
      created in the fascia lata of sheep and repaired with either an acellular dermal
      matrix (ADM) or urinary bladder matrix (UBM). After 1 or 3 months, the repair
      site was explanted for histological and mechanical analysis. RESULTS &
      CONCLUSION: Despite pre-implantation mechanical differences, both UBM and ADM
      demonstrated similar mechanical performance at 3 months. However, UBM was
      completely remodeled into site-appropriate tissue by 3 months, while ADM showed
      limited tissue incorporation.

PMID- 30182808
TI  - A scoping review on community mobilisation for maternal and child health in sub
      Saharan Africa: Impact on empowerment.
AB  - This review integrates evidence on community mobilisation (CM) for maternal and
      child health in sub-Saharan Africa (SSA) to identify the impact on empowerment.
      For the purposes of this review we use the following definition of CM: 'a
      capacity-building process through which community members, groups or
      organizations plan, carry out and evaluate activities on a participatory and
      sustained basis to improve their health and other conditions, either on their own
      initiative or stimulated by others', [Howard-Grabman, L., Storti, C., Hummer, P.,
      Pooler, B., & Geneva: USAID (2007). Demystifying community mobilization: An
      effective strategy to improve maternal and newborn health. Retrieved from
      http://pdf.usaid.gov/pdf_docs/pnadi338.pdf, p. 5]. A scoping review was chosen to
      conduct a search and analysis of the literature due to the broad, complex nature
      of the topic. The search yielded 136 articles, and 19 met the inclusion criteria.
      This review illustrates CM as an important research process for engaging the
      community, ensuring that interventions are meeting the needs of the community,
      take context into account and are sustainable. Community mobilisation was
      associated with positive behaviour change and/or health outcomes. However,
      community mobilisation was not defined or operationalised consistently among the
      identified studies. Empowerment was also not defined, measured, or reported on in
      the articles. This review provides recommendations for the reporting of CM and
      its influence on empowerment in communities in sub-Saharan Africa.

PMID- 30182809
TI  - Studies on the History of Pharmacy and the Evolution of Word Usage-Japanese
      Yakumi and Ryouri.
AB  - "Yakumi" and "Ryouri" are common vocabulary in modern Japanese. However, examples
      of their usage in terms of the Japanese meaning have not been found in general
      Chinese classics. Rather, conventionally they have been understood as kanji
      vocabulary originating in Japan. Therefore, through investigating and examining
      the sources and examples of both words, I found that they were derived from the
      original meanings of the Chinese words both in China and Japan, and the current
      meanings were adopted in Japan. It is very interesting to study the history of
      pharmacy and see in the processes and background that food was considered as a
      drug.

PMID- 30182810
TI  - Cocoa bean skin waste as potential raw material for liquid smoke production.
AB  - Cocoa bean skin is a waste of chocolate industries that mostly contains
      hemicellulose, cellulose, and lignin. This material shows to be a promising
      feedstock for the production of liquid smoke and charcoal. The study was aimed to
      analyse the influence of temperature and heating rate of cocoa bean skin
      pyrolysis to the production of liquid smoke. Optimization of pyrolysis process
      variables, i.e. by adjusting the suitable temperature and heating rate, is the
      key to obtain a high-quality product. The pyrolysis process was carried out using
      heating rates between 5 degrees C/min and 15 degrees C/min at three pyrolysis
      temperatures of 450 degrees C, 500 degrees C, and 550 degrees C. The yield of the
      produced liquid smoke was in the range of 18-23%. It showed that at a faster
      heating rate, the reaction produced more charcoal, ash, and water content for all
      pyrolysis temperatures. The highest yield of charcoal was ca. 39% with a caloric
      value of 22.97 MJ/kg, while the lowest ash and water content was in the range of
      16.5-19% and 6.5-8.5%, respectively. This result shows that the utilization of
      this organic waste compounds could be promising for large-scale production.

PMID- 30182811
TI  - Balancing Needs and Autonomy: The Involvement of Pregnant Women's Partners in
      Decisions About cfDNA.
AB  - Cell-free fetal DNA (cfDNA) screening is used to identify the presence of fetal
      genetic variants early in pregnancy. Patients' informed decision-making is
      central to the success of this new screen in clinical practice. Although research
      has focused on pregnant women's decision-making, little is known about partners'
      role and preferences as a member of the decision-making dyad. Using a grounded
      theory approach, this study analyzed 23 in-depth interviews to examine partners'
      perspectives about cfDNA screening and preferences with respect to their role in
      the decision-making process. Participants wished to be actively involved in
      testing decisions. They articulated a distinct set of needs and preferences in
      the decision-making process. Such involvement was hindered by several biological
      and logistical barriers. This study demonstrates the need to develop mechanisms
      that foster informed decision-making for cfDNA screening and related new
      reproductive genetic technologies that focus on not just the pregnant woman but
      also the decision-making dyad that includes her partner as well.

PMID- 30182812
TI  - A test of the CaR-FA-X mechanisms and depression in adolescents.
AB  - People who have depression have difficulty recalling specific autobiographical
      information (Sumner, (2011) The mechanisms underlying overgeneral
      autobiographical memory: An evaluative review of evidence for the Ca R-FA-X
      model. Clinical Psychology Review, 3231(1), 34-48). This is called overgeneral
      autobiographical memory (OGM) and is associated with the development and
      persistence of depression. Williams, Barnhofer, Crane, Hermans, Raes, Watkins, &
      Dalgleish (2007 Autobiographical memory specificity and emotional disorder.
      Psychological Bulletin, 133(1), 122-148) proposed that OGM is maintained by three
      mechanisms: capture and rumination (CaR), functional avoidance (FA), and impaired
      executive control (X), and integrated these into the CaR-FA-X model. The aim of
      this study was to assess OGM and test the CaR-FA-X model in adolescents with low
      mood. We recruited 29 young people aged 12-17 with elevated symptoms of
      depression and 29 with minimal symptoms of depression, matched for gender and
      age. After controlling for IQ, adolescents with elevated depression retrieved
      fewer specific memories, ruminated more, and had poorer working memory and verbal
      fluency than adolescents with minimal depression. The groups did not differ on
      measures of inhibition or functional avoidance. The CaR-FA-X model was therefore
      partially supported. These results confirm that there is a relationship between
      low mood and OGM in young people and that OGM may arise as consequence of
      impaired working memory and verbal fluency and cognitive interference due to
      rumination.

PMID- 30182814
TI  - Introduction: Medical tourism or movement for healthcare? Reflections on (inter
      )national cross-border mobility.

PMID- 30182813
TI  - Erratum.

PMID- 30182815
TI  - Drug-Coated Versus Plain Balloon Angioplasty In Arteriovenous Fistulas: A
      Randomized, Controlled Study With 1-Year Follow-Up (The Drecorest Ii-Study).
AB  - BACKGROUND AND AIMS: Stenosis due to intimal hyperplasia and restenosis after
      initially successful percutaneous angioplasty are common reasons for failing
      arteriovenous fistulas. The aim of this study was to evaluate the effect of drug
      coated balloons in the treatment of arteriovenous fistula stenosis. DESIGN:
      Single-center, parallel group, randomized controlled trial. Block randomized by
      sealed envelope 1:1. MATERIALS AND METHODS: A total of 39 patients with primary
      or recurrent stenosis in a failing native arteriovenous fistulas were randomized
      to drug-coated balloon (n = 19) or standard balloon angioplasty (n = 20). Follow
      up was 1 year. Primary outcome measure was target lesion revascularization.
      RESULTS: In all, 36 stenoses were analyzed; three patients were excluded due to
      technical failure after randomization. A total of 88.9% (16/18) in the drug
      coated balloon group was revascularized or occluded within 1 year, compared to
      22.2% (4/18) of the stenoses in the balloon angioplasty group (relative risk for
      drug-coated balloon 7.09). Mean time-to- target lesion revascularization was 110
      and 193 days after the drug-coated balloon and balloon angioplasty, respectively
      (p = 0.06). CONCLUSIONS: With 1-year follow-up, the target lesion
      revascularization-free survival after drug-coated balloon-treatment was clearly
      worse. The reason for this remains unknown, but it may be due to differences in
      the biological response to paclitaxel in the venous arteriovenous fistula-wall
      compared to its antiproliferative effect in the arterial wall after drug-coated
      balloon treatment of atherosclerotic occlusive lesions. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT03036241.

PMID- 30182816
TI  - Group versus Phase Velocity of Shear Waves in Soft Tissues.
AB  - Across the varieties of waves that have been studied in physics, it is well
      established that group velocities can be significantly greater than or less than
      phase velocities measured within comparable frequency bands, depending on the
      particular mechanisms involved. The distinction between group and phase
      velocities is important in elastography, because diagnoses are made based on
      shear wave speed estimations from a variety of techniques. We review the general
      definitions of group and phase velocity and examine their specific relations
      within an important general class of rheological models. For the class of tissues
      and materials exhibiting power law dispersion, group velocity is significantly
      greater than phase velocity, and simple expressions are shown to interrelate the
      commonly measured parameters. Examples are given from phantoms and tissues.

PMID- 30182817
TI  - Effect Of epigallocatechin-3-gallate on the pharmacokinetics of amlodipine in
      rats.
AB  - This study investigates the effect of epigallocatechin-3-gallate (EGCG), a major
      ingredient of green tea, on the pharmacokinetics of amlodipine in rats. The
      pharmacokinetics of orally administered amlodipine (1 mg/kg) with or without EGCG
      pretreatment (30 mg/kg/day for 10 days) were investigated. Plasma concentrations
      of amlodipine were determined by using a sensitive and reliable liquid
      chromatography with tandem mass spectroscopy (LC-MS/MS) method. The effects of
      EGCG on the metabolic stability of amlodipine were investigated by using rat
      liver microsome incubation systems. The results indicated that when the rats were
      pretreated with EGCG, the Cmax of amlodipine increased from 16.32 +/- 2.57 to
      21.44 +/- 3.56 ng/mL (p < 0.05), the Tmax decreased from 5.98 +/- 1.25 to 4.01 +/
      1.02 h (p < 0.05), and the AUC0-t increased from 258.12 +/- 76.25 to 383.34 +/-
      86.95 MUg h L-1 (p < 0.05), which suggested that the pharmacokinetic behavior of
      amlodipine was affected after oral co-administration of EGCG. Additionally, the
      metabolic half-life was prolonged from 31.3 +/- 5.6 to 52.6 +/- 7.9 min (p <
      0.05) with the pretreatment of EGCG. It can be speculated that the drug-drug
      interaction between EGCG and amlodipine might occur, which might have resulted
      from the metabolism inhibition of amlodipine by EGCG when they were co
      administered.

PMID- 30182818
TI  - [Test Reviews].

PMID- 30182820
TI  - [Authors].

PMID- 30182819
TI  - [Personality Assessment as Contribution to Diagnostic Differentiation Between
      ADHD and RAD in Middle Childhood].
AB  - Personality Assessment as Contribution to Diagnostic Differentiation Between ADHD
      and RAD in Middle Childhood Early and prolonged social and emotional deprivation
      can result in symptoms of both ADHD and attachment disorder (RAD). The present
      study compares children between 7 and 13 years of age diagnosed with either ADHD
      or RAD, regarding their disorder specific behavior by using the Conners Rating
      Scale, a RAD screening scale, the overall psychopathology in the CASCAP-D, and
      the children's personality using the California Child-Q-sort (CCQ). The RAD group
      showed an increased overall psychopathology score and both increased ADHD and RAD
      symptomatology. In addition, they also were characterized as lower in self
      regulatory personality characteristics (e. g. ego-resiliency). The results
      suggest that children with a RAD diagnosis do not show two comorbid disorders
      (RAD plus ADHD) but are characterized by an even more intense deficit of self
      regulation in social and emotional contexts, compared to the children of the pure
      ADHD group. This should be considered in diagnosis and treatment.

PMID- 30182823
TI  - [Symptoms of Attachment Disorder, Behavioral Regulation and Physiological Stress
      in Institutionalized Children].
AB  - Symptoms of Attachment Disorder, Behavioral Regulation and Physiological Stress
      in Institutionalized Children The aim of the study was to investigate the
      influence of attachment status (availability of a specific caregiver) and
      caregiving quality on behavioral and physiological adaptation and attachment
      disorder in institutionalized children. In a sample of children from a Georgian
      children's home, attachment disorder symptoms were assessed by interview and
      attachment and exploration behavior as well as self-regulatory behavior were
      assessed by observation in the natural group setting as well in structured dyadic
      situations. The child circadian cortisol level was determined to assess
      physiological adaption. Quality of caregiving was assessed in terms of
      sensitivity by observation. While attachment status affected the occurrence of
      attachment disorder symptoms and physiological stress, patterns of regulation in
      terms of attachment-exploration-balance and self-regulatory behavior were
      predicted by caregiver sensitivity.

PMID- 30182821
TI  - [Multifamilygroups as a Psychosocial and Contextoriented Intervention for Somatic
      Illness and Disability].
AB  - Multifamilygroups as a Psychosocial and Contextoriented Intervention for Somatic
      Illness and Disability This paper provides a detailed description of a multi
      family group (MFG) intervention designed for children with disabilities or
      chronical somatic disease and their families based on a systemic model. A mixed
      methods study examines the perspectives of the participating family members
      regarding specific intervention components and the therapeutic process and its
      outcomes of this heterogeneous, closed MFG. Problem-centered interviews and
      questionnaires were used. Attendance of and satisfaction with the group were
      high. Specific intervention components such as the provided therapeutic
      environment and the mutual support that was facilitated by offering different
      opportunities for contact with families in similar situations are highlighted as
      particularly helpful. Increased feelings of parental togetherness and competence
      were reported. Results suggest that this MFG for families of children with
      chronic diseases or disabilities is highly feasible for these families.

PMID- 30182824
TI  - [Strategies of Emotion Regulation in Adolescents with Depression].
AB  - Strategies of Emotion Regulation in Adolescents with Depression The present study
      investigated differences between adolescents with a depressive disorder and
      control subjects in their adaptive und maladaptive regulation of negative
      emotions. We assessed emotion regulation strategies using the German self-report
      questionnaire FEEL-KJ in a sample of adolescents with depression (n = 57) and
      controls (n = 57). We found that adolescents with depression reported using less
      adaptive strategies and more maladaptive strategies for dealing with the negative
      emotions anxiety, sadness and anger than control subjects. Our findings indicate
      that adolescents with depression showed difficulties with regard to different
      negative emotions that should be considered in intervention.

PMID- 30182826
TI  - Novel Bioinformatics and Systems Biology approaches and techniques in
      Pharmaceutical and Biochemical Sciences.

PMID- 30182827
TI  - Stem Cells and Cartilage Tissue Engineering.

PMID- 30182828
TI  - New Experimental and Computational Tools for Drug Discovery: From Chemistry to
      Biology. Metabolomics, Pharmacokinetics, and Medicinal Chemistry. Part - IV.

PMID- 30182829
TI  - A Brief Review on Software Tools in Generating Chou's Pseudo-factor
      Representations for All Types of Biological Sequences.
AB  - BACKGROUND: In the post-genome age, it is more urgent to understand the functions
      of genes and proteins. Since experimental methods are usually costly and time
      consuming, computational predictions are recognized as an alternative approach.
      In developing a predictive method for functional genomics and proteomics, one of
      the most important steps is to represent biological sequences with a fixed length
      numerical form, which can be further analyzed using machine learning algorithms.
      Chou's pseudo-amino acid compositions and the pseudo k-nucleotide compositions
      are algorithms for this purpose. CONCLUSION: Since the appearance of these
      algorithms, several software tools have been developed as implementations. These
      software tools facilitate the application of these algorithms. As these software
      tools are developed with different technologies and for different application
      scenarios, we will briefly review the technical aspect of these software tools in
      this short review.

PMID- 30182830
TI  - A Comprehensive Review of In silico Analysis for Protein S-sulfenylation Sites.
AB  - BACKGROUND: Cysteine S-sulfenylation is a major type of dynamic post
      translational modification of the protein that plays an important role in
      regulating many biological processes in both of prokaryotic and eukaryotic
      species. To understand the function of S-sulfenylated proteins, identification of
      S-sulfenylation sites is an essential step. Due to numerous restrictions of
      experimental methods, computational prediction of the potential S-sulfenylation
      sites becomes popular. In this review, we discuss the recent development and
      challenges in protein S-sulfenylation site prediction from the available
      datasets, algorithms and accessible services. We also demonstrate the encountered
      limitation and future perspective of the computational prediction tools.
      CONCLUSION: The development of S-sulfenylation site prediction and their
      application is an emerging field of protein bioinformatics research. Accurate
      predictors are expected to identify general and species-specific S-sulfenylation
      sites when more experimental annotation data are available. Combining
      experimental and computational technologies will definitely accelerate an
      understanding of protein S-sulfenylation, discovering regulatory networks in
      living organisms.

PMID- 30182831
TI  - Isolation, Purification and Characterisation of a D-galactose and N-acetyl-D
      galactosamine Specific Lectin from Marine Sponge Fasciospongia cavernosa.
AB  - BACKGROUND: Marine sponges, belonging to the phylum Porifera, are gaining more
      attention by researchers and industrial sectors from all over the world due to
      their ability to produce a variety of bioactive secondary metabolites that have
      many applications including drug discovery. Marine sponges are a promising source
      of bioactive lectins, which are structurally diverse, many of them in the form of
      glycoproteins. OBJECTIVE: To purify and characterize lectin from a marine sponge
      Fasciospongia cavernosa and to study its antibacterial activity. METHOD: Lectin
      from a marine sponge Fasciospongia cavernosa was purified by guar gum affinity
      chromatography and checked for its biophysical and antibacterial properties. The
      lectin was subjected to evaluation for inhibition of microbial growth against
      bacteria by aggregation test. The activity of FCL against the biofilms formed by
      P. aeruginosa was also carried out. Biofilm is defined as the undesirable
      accumulation of microorganisms on artificial surfaces immersed in a common
      matrix. The effect of FCL on biofilm-forming gram negative bacteria P. aeruginosa
      was tested by crystal violet assay. RESULTS: This lectin, named FCL, has a
      molecular weight of 80 KDa approximately, was found to agglutinate human ABO,
      rat, rabbit and chicken erythrocytes. The hemagglutinating activity of FCL was
      reduced by demetallisation with E.D.T.A and regained by the addition of Ca2+,
      Mg2+, Mn2+, Ba2+ and Fe2+, which shows the metal dependency of the lectin. The
      hemagglutinating activity by the lectin was inhibited by D-galactose and N-acetyl
      D-galactosamine. The lectin was stable over a range of pH from 2 to 10.5, and up
      to a temperature 70 degrees C for 20 min. FCL agglutinated B. subtilis, S. aureus
      and P. aeruginosa and was able to reduce biofilm mass formed by P. aeruginosa.
      Thus, the marine sponge F. cavernosa lectin, FCL could be used as an
      antibacterial agent. FCL significantly reduced the biomass of bacterial biofilm
      tested. Biofilm mass of P. aeruginosa, K. pneumoniae and E. coli were decreased
      in a dose dependent manner. CONCLUSION: A novel lectin was isolated and purified
      from marine sponge F. cavernosa. FCL, a galactose-binding lectin displayed
      considerable antimicrobial activity in vitro, particularly against gram-positive
      bacteria and also exhibited a strong antibiofilm activity.

PMID- 30182832
TI  - Purification, characterization of alkaline cold active lipase from Acinetobacter
      radioresistens PR8 and development of a new zymography method for lipase
      detection.
AB  - Lipase zymography methods use costly chromogenic substrates and indicator dyes
      and are few in numbers. In this present work, an alkalophilic lipase producing
      bacterium was isolated from soil; screened for extracellular lipase activity and
      identified to be Acinetobacter radioresistens PR8 by 16S rRNA sequencing (Genbank
      accession ID: MF073322). Enzyme production kinetics showed maximum production
      (4.16 U/ml at pH 9) of the enzyme after 72 h. The lipase activity was found to be
      highest in olive oil (1% v/v; 8.1 U/ml). Low molecular weight (27 kDa) alkaline
      (pH 9) cold active (20  degrees C) lipase was purified from Acinetobacter
      radioresistens PR8. Lipase was characterized using PMF, FT-IR and its high
      conformational stability (Transition temperature: 122.3  degrees C) were
      attributed to its DSC spectrum. The importance of magnesium and sodium ions for
      enhancing lipase activity was obtained from flux balance analysis. Based on the
      lipase activating role of Mn2+ and Na+ ions, optimum temperature, pH with no
      chromogenic substrates and indicator dyes, a new in gel zymography method for
      lipase detection was developed.

PMID- 30182833
TI  - RWLPAP: Random Walk for lncRNA-protein Associations Prediction.
AB  - BACKGROUND: During recent years, a lot of experimental studies have shown that
      lncRNA-binding proteins play a key role in many biomedical processes. Therefore,
      it is important to predict the potential lncRNA-protein associations in
      biomedical researches. OBJECTIVE: To predict the associations between lncRNAs and
      proteins more reliably and more efficiently. METHOD: Considering the limitations
      of previous computational methods, we introduce a predictive model called Random
      Walk for lncRNA-Protein Associations Prediction (RWLPAP). It belongs to semi
      supervised learning algorithms, and thus RWLPAP successfully avoids the
      difficulty of extracting negative data sets and features. RESULTS: By the leave
      one-out cross validation, we compare RWLPAP with previous methods and conclude
      that RWLPAP has an AUC of 0.88, which is significantly higher than other three
      models. It suggests that RWLPAP is more reliable and effective in predicting the
      interactions between lncRNAs and proteins. CONCLUSION: In the case study,
      according to the rank of predictive scores, we can find that the scores of some
      lncRNA-protein associations are highly ranking by our method when is compared
      with other three methods. It indicates that our method is very effective and
      comprehensive. Therefore, we can expect that RWLPAP will be a useful
      bioinformatic tool in the future.

PMID- 30182834
TI  - Five Years of the KNIME Vernalis Cheminformatics Community Contribution.
AB  - : Since the official release as a KNIME Community Contribution in June 2013, the
      Vernalis KNIME nodes have increased from a single node (the 'PDB Connector'
      node), to around 126 nodes (November 2017; Version 1.12.0); furthermore, a number
      of nodes have been adopted into the core KNIME product. In this review, we
      provide a brief timeline of the development of the current public release and an
      overview of the current nodes. We will focus in more detail on three particular
      areas: nodes accessing publicly available information via webservices, nodes
      providing cheminformatics functionality without recourse to a cheminformatics
      toolkit, and nodes using one of the cheminformatics toolkits present in KNIME. We
      will conclude with a number of case studies demonstrating the use of KNIME at
      Vernalis.

PMID- 30182835
TI  - Prognostic Impact of Tissue Inhibitor of Metalloproteinase-1 in Non-Small Cell
      Lung Cancer: Systematic Review and Meta-Analysis.
AB  - BACKGROUND AND OBJECTIVES: Tissue inhibitor of metalloproteinase-1 (TIMP-1) is a
      multifunctional natural matrixin inhibitor that is generally considered a
      negative regulator of cancer metastasis. Clinical studies reporting the
      prognostic value of TIMP-1 in non-small cell lung cancer (NSCLC) are
      inconsistent. Therefore, the present study aimed to determine the prognostic
      impact of TIMP-1 expression in NSCLC. METHODS: Appropriate studies with full-text
      articles were identified in searches of the China National Knowledge
      Infrastructure (CNKI), Cochrane Library, PubMed, and Web of Science databases up
      to March 7, 2018. The pooled hazard ratio (HR) of overall survival with a 95%
      confidence interval (95% CI) was employed to assess the relationship between
      expression of TIMP-1 and NSCLC patient survival. RESULTS: The meta-analysis
      comprised 40 studies including 3,194 patients. Study outcomes indicated that high
      TIMP-1 expression is independently associated with poor overall survival (HR:
      1.60; 95% CI: 1.50, 1.69; P < 0.00001) with 61% of heterogeneity. In addition, we
      analyzed subgroups, including ethnicities, histological types, percentage of TIMP
      1 expression levels, specimens, and tumor stage. All results were statistically
      significant. The outcome of our meta-analysis indicates that high expression
      levels of TIMP-1 are correlated with poor prognosis in patients with NSCLC.
      CONCLUSIONS: Expression levels of TIMP-1 represent a potential prognostic
      biomarker in NSCLC patients in addition to being a possible therapeutic target.

PMID- 30182836
TI  - Advances in Docking.
AB  - BACKGROUND: Design of small molecules which are able to bind to the protein
      responsible for a disease is the key step of the entire process of the new
      medicine discovery. Atomistic computer modeling can significantly improve
      effectiveness of such design. The accurate calculation of the free energy of
      binding a small molecule (a ligand) to the target protein is the most important
      problem of such modeling. Docking is one of the most popular molecular modeling
      methods for finding ligand binding poses in the target protein and calculating
      the protein-ligand binding energy. This energy is used for finding the most
      active compounds for the given target protein. This short review aims to give a
      concise description of distinctive features of docking programs focusing on
      computation methods and approximations influencing their accuracy. METHODS: This
      review is based on the peer-reviewed research literature including author's own
      publications. Main features of several representative docking programs are
      briefly described focusing on their characteristics influencing docking accuracy:
      force fields, energy calculations, solvent models, algorithms of the best ligand
      pose search, global and local optimizations, ligand and target protein
      flexibility, and the simplifications made for the docking accelerating. Apart
      from other recent reviews focused mainly on the performance of different docking
      programs, in this work an attempt is made to extract the most important
      functional characteristics defining the docking accuracy. Also a roadmap for
      increasing the docking accuracy is proposed. This is based on the new generation
      of docking programs which have been realized recently. These programs and
      respective new global optimization algorithms are described shortly. RESULTS:
      Several popular conventional docking programs are considered. Their search of the
      best ligand pose is based explicitly or implicitly on the global optimization
      problem. Several algorithms are used to solve this problem, and among them the
      heuristic genetic algorithm is distinguished by its popularity and an elaborate
      design. All conventional docking programs for their acceleration use the
      preliminary calculated grids of protein-ligand interaction potentials or
      preferable points of protein and ligand conjugation. These approaches and
      commonly used fitting parameters restrict strongly the docking accuracy. Solvent
      is considered in exceedingly simplified approaches in the course of the global
      optimization and the search for the best ligand poses. More accurate approaches
      on the base of implicit solvent models are used frequently for more careful
      binding energy calculations after docking. The new generation of docking programs
      are developed recently. They find the spectrum of low energy minima of a protein
      ligand complex including the global minimum. These programs should be more
      accurate because they do not use a preliminary calculated grid of protein-ligand
      interaction potentials and other simplifications, the energy of any conformation
      of the molecular system is calculated in the frame of a given force field and
      there are no fitting parameters. A new docking algorithm is developed and
      fulfilled specially for the new docking programs. This algorithm allows docking a
      flexible ligand into a flexible protein with several dozen mobile atoms on the
      base of the global energy search. Such docking results in improving accuracy of
      ligand positioning in the docking process. The adequate choice of the method of
      molecular energy calculations also results in the better docking positioning
      accuracy. An advance in the application of quantum chemistry methods to docking
      and scoring is revealed. CONCLUSION: The findings of this review confirm the
      great demand in docking programs for discovery of new medicine substances with
      the help of molecular modeling. New trends in docking programs design are
      revealed. These trends are focused on the increase of the docking accuracy at the
      expense of more accurate molecular energy calculations without any fitting
      parameters, including quantum-chemical methods and implicit solvent models, and
      by using new global optimization algorithms which make it possible to treat
      flexibility of ligands and mobility of protein atoms simultaneously. Finally, it
      is shown that all the necessary prerequisites for increasing the docking accuracy
      can be accomplished in practice.

PMID- 30182837
TI  - Close interplay of nitro-oxidative stress, advanced glycation end products and
      inflammation in inflammatory bowel diseases.
AB  - BACKGROUND: Inflammatory bowel disease (IBD) exhibits no defined aetiology.
      However, such factors as genetic and nitro-oxidative stress are associated with
      chronic inflammation and IBD progression to colorectal cancer (CRC). The present
      review discusses the association of nitro-oxidative stress, inflammation and
      advanced glycation end products (AGE) and its corresponding receptor (RAGE) in
      IBD and examines the connection between these factors and nuclear factors, such
      as nuclear factor kappa B (NF- kappaB), factor-erythroid 2-related factor-2
      (Nrf2), and p53 mutant (p53M). METHODS: We searched the PubMed, ScienceDirect and
      Web of Science databases using a combination of the following terms: IBD, CRC,
      oxidative stress, inflammation, NF-kappaB, Nrf2, p53M, AGE and RAGE. RESULTS:
      Oxidative stress and inflammation activated two cellular pathways, the nuclear
      expression of pro-inflammatory, pro-oxidant and pro-oncogenic genes based on NF
      kappaB and p53M, which is associated with NF-kappaB activation, deoxyribonucleic
      acid (DNA) damage and the expression of pro-oncogenic genes. Nrf2 stimulates the
      nuclear expression of enzymatic and non-enzymatic antioxidant systems and anti
      inflammatory genes, and is inhibited by chronic oxidative stress, NF-kappaB and
      p53M. AGE/RAGE are involved in inflammation progression because RAGE
      polymorphisms and increased RAGE levels are found in IBD patients. Alterations of
      these pathways in combination with oxidative damage are responsible for IBD
      symptoms and the progression to CRC. CONCLUSIONS: IBD is an inflammatory and
      nitro-oxidative stress-based bowel disease. Achieving a molecular understanding.

PMID- 30182838
TI  - Lipids as biomarkers of cancer and bacterial infections.
AB  - Lipids are ubiquitous molecules, known to play important roles in various
      cellular processes. Alterations to the lipidome can therefore be used as a read
      out of the signs of disease, highlighting the importance to consider lipids as
      biomarkers in addition of nucleic acid and proteins. This mini-review exposes the
      current knowledge and limitations of the use of lipids as biomarkers of the top
      global killers which are cancer and bacterial infections.

PMID- 30182839
TI  - Tumor Vasculature Targeted TNFalpha Therapy: Reversion of Microenvironment Anergy
      and Enhancement of the Anti-tumor Efficiency.
AB  - Tumor cells and tumor-associated stromal cells such as immune, endothelial and
      mesenchimal cells create a tumor microenvironment (TME) which allows tumor cell
      promotion, growth and dissemination while dampening the anti-tumor immune
      response. Efficient anti-tumor interventions have to keep into consideration the
      complexity of the TME and take advantage of immunotherapy and chemotherapy
      combined approaches. Thus, the aim of tumor therapy is to directly hit tumor
      cells and reverse endothelial and immune cell anergy. Selective targeting of
      tumor vasculature using TNFalpha-associated peptides or antibody fragments in
      association with chemotherapeutic agents has been shown able to exert a potent
      stimulatory effect on endothelial cells as well as on innate and adaptive immune
      responses. These drug combinations reducing the dose of single agents employed
      have led to minimize the associated side-effects. In this review we will analyze
      different TNFalpha-mediated tumor vessel-targeted therapies in both humans and
      tumor mouse models, with emphasis on the role played by the cross-talk between
      natural killer and dendritic cells and on the ability of TNFalpha to trigger
      tumor vessel activation and normalization. The improvement of the TNFalpha-based
      therapy with anti-angiogenic immunomodulatory drugs that may convert the TME from
      immunosuppressive to immunostimulant, will be discussed as well.

PMID- 30182840
TI  - An overview of antiretroviral agents for treating HIV infection in paediatric
      population.
AB  - Paediatric Acquired ImmunoDeficiency Syndrome (AIDS) is a life-threatening and
      infectious disease in which the Human Immunodeficiency Virus (HIV) is mainly
      transmitted through Mother-To-Child Transmission (MTCT) during pregnancy, labour
      and delivery, or breastfeeding. This review provides an overview of the distinct
      therapeutic alternatives to abolish the systemic viral replication in paediatric
      HIV-1 infection. Numerous classes of antiretroviral agents have emerged as
      therapeutic tools for downregulation of different steps in the HIV replication
      process. These classes encompass Non-Nucleoside Analogue Reverse Transcriptase
      Inhibitors (NNRTIs), Nucleoside/Nucleotide Analogue Reverse Transcriptase
      Inhibitors (NRTIs/NtRTIs), INtegrase Inhibitors (INIs), Protease Inhibitors
      (PIs), and Entry Inhibitors (EIs). Co-administration of certain antiretroviral
      drugs with Pharmacokinetic Enhancers (PEs) may boost the effectiveness of the
      primary therapeutic agent. The combination of multiple antiretroviral drug
      regimens (Highly Active AntiRetroviral Therapy - HAART) is currently the standard
      therapeutic approach for HIV infection. So far, the use of HAART offers the best
      opportunity for prolonged and maximal viral suppression, and preservation of the
      immune system upon HIV infection. Still, the frequent administration of high
      doses of multiple drugs, their inefficient ability to reach the viral reservoirs
      in adequate doses, the development of drug resistance and the lack of patient
      compliance compromise the complete HIV elimination. The development of
      nanotechnology-based drug delivery systems may enable targeted delivery of
      antiretroviral agents to inaccessible viral reservoir sites at therapeutic
      concentrations. In addition, the application of Computer-Aided Drug Design (CADD)
      approaches has provided valuable tools for the development of anti-HIV drug
      candidates with favourable pharmacodynamics and pharmacokinetic properties.

PMID- 30182841
TI  - Lithium - pharmacological and toxicological aspects: the current state of the
      art.
AB  - Lithium is the smallest monovalent cation with many different biological effects.
      Although lithium is present in pharmacotherapy of psychiatric illnesses for
      decades, its precise mechanism of action is still not clarified. Today lithium
      represents first-line therapy for bipolar disorders (because it possesses both
      antimanic and antidepressant properties) and the adjunctive treatment for major
      depression (due to its antisuicidal effects). Beside, lithium showed some
      protective effects in neurological diseases including acute neural injury,
      chronic degenerative conditions, Alzheimer's disease as well as in treating
      leucopenia, hepatitis and some renal diseases. Recent evidence suggested that
      lithium also possesses some anticancer properties due its inhibition of glycogen
      synthase kinase 3 beta (GSK3beta) which is included in regulation of a lot of
      important cellular processes such as: glycogen metabolism, inflammation,
      immunomodulation, apoptosis, tissue injury, regeneration etc. Although recent
      evidence suggested a potential utility of lithium in different conditions, its
      broader use in clinical practice still trails. The reason for this is a narrow
      therapeutic index of lithium, numerous toxic effects in various organ systems and
      some clinically relevant interactions with other drugs. Additionally, it is
      necessary to perform more preclinical as well clinical studies in order to
      precise therapeutic range of lithium, as well as its detailed mechanism of
      action. The aim of this review is to summarize the current knowledge concerning
      pharmacological and toxicological effects of lithium.

PMID- 30182842
TI  - Pyridine and Pyrimidine Derivatives as Privileged Scaffolds in Biologically
      Active Agents.
AB  - Pyridine and pyrimidine derivatives have received great interest in recent
      pharmacological research, being effective in the treatment of various
      malignancies, such as myeloid leukemia, breast cancer and idiopathic pulmonary
      fibrosis. Most of the FDA approved drugs show a pyridine or pyrimidine core
      bearing different substituents. Aim of this review is to describe the most recent
      reports in this field, with reference to the new discovered pyridine- or
      pyrimidine-based drugs, to their synthesis and to the evaluation of the most
      biologically active derivatives. The corresponding benzofused heterocyclic
      compounds, i.e. quinolines and quinazolines, are also reported.

PMID- 30182843
TI  - Fructose-1,6-bisphosphatase Inhibitors: A review of Recent (2000-2017) Advances
      and Structure-Activity Relationship Studies.
AB  - Diabetes mellitus, commonly referred to as diabetes, is the 8th leading cause of
      death worldwide. As of 2015, approximately 415 million people were estimated to
      be diabetic worldwide, type 2 diabetes being the most common accounting for
      approximately 90-95% of all diagnosed cases with increasing prevalence. Fructose
      1,6-bisphosphatase is one of the important therapeutic targets recently
      discovered to treat this chronic disease. In this focus review, we have
      highlighted recent advances and structure-activity relationship studies in
      discovery and development of different fructose-1,6-bisphosphatase inhibitors
      reported since the year 2000.

PMID- 30182844
TI  - Plant-Derived Products as Antibacterial and Antifungal Agents in Human Health
      Care.
AB  - A number of papers reporting antimicrobial properties of extracts, essential
      oils, resins and various classes of compounds isolated from higher plants has
      been published in recent years; however, a comprehensive analysis of plant
      derived antimicrobial agents currently applied in practice for improvement of
      human health is still lacking. This review summarizes data on clinical efficacy,
      antimicrobial effects and the chemistry of commercially available antibacterial
      and antifungal agents of plant origin currently used in the prevention and
      treatment of gastrointestinal, oral, respiratory, skin, and urinary infections.
      As a result of an analysis of the literature, more than 40 plant-derived over-the
      counter pharmaceuticals, dietary supplements, cosmetics, herbal medicines, and
      functional foods containing complex mixtures (e.g. Glycyrrhiza glabra extract,
      Melaleuca alternifolia essential oil, and Pistacia lentiscus resin), pure
      compounds (e.g. benzoic acid, berberine, eucalyptol, salicylic acid and thymol)
      as well as their derivatives and complexes (e.g. bismuth subsalicylate and zinc
      pyrithione) have been identified. The effectiveness of many of these products is
      illustrated by results of clinical trials and supported by data on their in vitro
      antimicrobial activity. A broad spectrum of various commercial products currently
      available on the market and their well-documented clinical efficacy suggests that
      plants are prospective sources for the identification of new types of
      antimicrobial agents in future. Innovative approaches and methodologies for
      effective proof-of-concept research and the development of new types of plant
      derived products effective against recently emerging problems related to human
      microbial diseases (e.g. antimicrobial resistance) are also proposed in this
      review.

PMID- 30182845
TI  - The healing effects of spices in chronic diseases.
AB  - Spices are not only just herbs used in culinary for improving the taste of
      dishes. They are also sources of a numerous bioactive compounds significantly
      beneficial for health. They have been used since ancient times because of their
      antimicrobial, anti-inflammatory and carminative properties. Several scientific
      studies have suggested their protective role against chronic diseases. In fact,
      their active compounds may help in arthritis, neurodegenerative disorders
      (Alzheimer's, Parkinson, Huntington's disease, amyotrophic lateral sclerosis,
      etc.), diabetes, sore muscles, gastrointestinal problems and many more. In the
      present study, possible roles of spices and their active components, in chronic
      diseases (cancer, arthritis, cardiovascular diseases, etc.) along with their
      mechanism of action have been reviewed.

PMID- 30182846
TI  - Exosome-like nanovectors for drug delivery in cancer.
AB  - Cancer treatment still represents a formidable challenge, despite substantial
      advancements in available therapies being made over the past decade. One major
      issue is poor therapeutic efficacy due to a lack of specificity and low
      bioavailability. The progress of nanotechnology and the development of a variety
      of nanoplatforms have had a significant impact in improving the therapeutic
      outcome of chemotherapeutics. Nanoparticles can overcome various biological
      barriers and localize at tumor site, while simultaneously protecting a
      therapeutic cargo and increasing its circulation time. Despite this, due to their
      synthetic origin, nanoparticles are often detected by the immune system and
      preferentially sequestered by filtering organs. Exosomes have recently been
      investigated as suitable substitutes for the shortcomings of nanoparticles due to
      their biological compatibility and particularly small size (i.e., 30-150 nm). In
      addition, exosomes have been found to play important roles in cell communication,
      acting as natural carriers of biological cargoes throughout the body. This review
      aims to highlight the use of exosomes as drug delivery vehicles for cancer and
      showcases the various attempts used to exploit exosomes with a focus on the
      delivery of chemotherapeutics and nucleic acids.

PMID- 30182847
TI  - Hydrogel-clay nanocomposites as carriers for controlled release.
AB  - The present review aims to summarize the research efforts undertaken in the last
      few years in the development and testing of hydrogel-clay nanocomposites proposed
      as carriers for controlled release of diverse drugs. Their advantages,
      disadvantages and different compositions of polymers/biopolymers with diverse
      types of clays, as well as their interactions are discussed. Illustrative
      examples of studies regarding hydrogel-clay nanocomposites are detailed in order
      to underline the progressive researches on hydrogel-clay-drug pharmaceutical
      formulations able to respond to a series of demands for the most diverse
      applications. Brief descriptions of the different technique used for the
      characterization of the obtained complex hybrid materials such as: swelling, TGA,
      DSC, FTIR, XRD, mechanical, SEM, TEM and biology tests, are also included.
      Enlightened by the presented data, we can suppose that hydrogel-clay
      nanocomposites will still be a challenging subject of global assiduous
      researches. We can dare to dream to an efficient drug delivery platform for the
      treatment of multiple affection concomitantly, these being undoubtedly like "a
      tree of life" bearing different kind of fruits and leafs proper for human
      healing.

PMID- 30182848
TI  - Streptococcal Collagen-like Protein 1 Binds Wound Fibronectin: Implications in
      Pathogen Targeting.
AB  - Group A Streptococcus (GAS) infections are responsible for significant morbidity
      and mortality worldwide. The outlook for an effective global vaccine is reduced
      because of significant antigenic variation among GAS strains worldwide. Other
      challenges in GAS therapy include the lack of common access to antibiotics in
      developing countries, as well as allergy to and treatment failures with
      penicillin and increasing erythromycin resistance in the industrialized world. At
      the portal of entry, GAS binds to newly deposited extracellular matrix, which is
      rich in cellular fibronectin isoforms with extra domain A (EDA, also termed
      EIIIA) via the surface adhesin, the streptococcal collagen-like protein 1 (Scl1).
      Recombinant Scl1 constructs, derived from diverse GAS strains, bind the EDA loop
      segment situated between the C and C' beta-strands. Despite the sequence
      diversity in Scl1 proteins, multiple sequence alignments and secondary structure
      predictions of Scl1 variants, as well as crystallography and homology modeling
      studies, point to a conserved mechanism of Scl1-EDA binding. We propose that
      targeting this interaction may prevent the progression of infection. A synthetic
      cyclic peptide, derived from the EDA C-C' loop, binds to recombinant Scl1 with a
      micromolar dissociation constant. This review highlights the current concept of
      EDA binding to Scl1 and provides incentives to exploit this binding to treat GAS
      infections and wound colonization.

PMID- 30182849
TI  - Targeting Long Non-Coding RNAs in Nervous System Cancers: New Insights in
      Prognosis, Diagnosis and Therapy.
AB  - Long non-coding RNAs (lncRNAs) constitute one of the most broad and diverse
      classes of cellular transcripts, playing key roles as regulatory molecules in
      many biological processes. Although the biology of lncRNAs is a new and emerging
      field of research, several studies have already shown that alterations in the
      expression of lncRNAs are associated with the development and progression of
      cancer in different organs and tissues, including central and peripheral nervous
      system. In this review, we summarize the oncogenic and tumor suppressive roles of
      lncRNAs in malignant tumors of the nervous system, such as glioma and
      neuroblastoma, focusing on their functional interactions with DNA, other RNA and
      protein molecules. We further discuss the potential use of lncRNAs as biomarkers
      for diagnosis, prognosis and tumor treatment. Gaining insight into the functional
      association between nervous system malignancies and lncRNAs could offer new
      perspectives to the development of promising therapeutic tools against cancer.

PMID- 30182850
TI  - Therapeutic Macromolecular Iron Chelators.
AB  - Iron is an key element for every single living processes. On a fundamental level,
      targeting iron is a valuable approach for the treatment of disorders caused by
      iron overload. Utilizing iron chelators as therapeutic agents has received
      expanding consideration in chelation therapy. Approved low molecular weight (MW)
      iron chelators to treat iron overload may experience short half-lives and
      toxicities prompting moderately high adverse effects. In recent years
      polymeric/macromolecular iron chelators have received attention as therapeutic
      agents. Polymeric iron chelators show unique pharmaceutical properties that are
      different to their conventional small molecule counterparts. These polymeric iron
      chelators possess longer plasma half-lives and reduced toxicities, thus
      exibitting a significant supplement to currently using low MW iron chelator
      therapy. In this review we have briefly discussed polymeric iron chelators and
      factors to be considered when designing clinically valuable iron chelators. We
      have also discussed applications of polymeric iron chelators in the diseases
      caused by iron overload associated with transfusional hemosiderosis,
      neurodegenerative disorders, malaria and cancer. With this, research findings for
      new polymeric iron chelators are also covered.

PMID- 30182851
TI  - The Current Status and Perspectives of Delivery Strategy for Boron-based Drugs.
AB  - Boron-containing compounds are essential micronutrients for animals and plants
      despite their low-level natural occurrence. They can strengthen the cell walls of
      the plants and they play important role in supporting bone health. However,
      surprisingly, boron-containing compounds are seldom found in pharmaceutical
      drugs. In fact, there are no inherent disadvantages reported so far in terms of
      the incorporation of boron into medicines. Indeed, drugs based on boron
      containing compounds, such as tavaborole (marked name Kerydin) and bortezomib
      (trade name Velcade) have been investigated and they are used in clinical
      treatment. In addition, following the advanced development of boron neutron
      capture therapy and a new emerging proton boron fusion therapy, more boron
      containing medicinals are to be expected. This review discusses the current
      status and perspectives of delivery strategy for boron-containing drugs.

PMID- 30182852
TI  - Therapeutic approaches for the management of sleep disorders in geriatric
      population.
AB  - OBJECTIVE: Aging is a natural biological phenomenon that occurs in human beings.
      With increasing of age, there is an appearance of deleterious changes related
      with progression onto pathological conditions, including hypertension, heart
      disease, diabetes, hearing and vision impairments, as well as sleep disorders. It
      is important to recognize that some sleep disturbances reported by aged subjects
      include insomnia, obstructive sleep apnea, restless legs syndrome, among others.
      Moreover, accumulating evidence indicates that coexistence of medical issues with
      sleep disorders constitutes clinical challenges for treatment of comorbidities in
      elderly. Here, we have attempted to review and summarize the available literature
      that assess the sleep disturbances in aging. In addition, we highlight the
      management of sleep disorders associated with aging. Due to particular health
      condition of aged adults, the development of effective pharmacological
      interventions for sleep disorders treatment in aging is warranted. METHOD: Review
      of studies retrieved from the PubMed. RESULTS: The sleep-wake cycle includes
      abnormalities classified as sleep disorders. Comorbidity between sleep
      disturbances and aging-related health issues will represent a public health
      challenge to be address in the near future. Moreover, this scenario will suggest
      an area that require further drug investigation and design of new pharmacological
      and pharmaceutical strategies to treat sleep disorders in elderly population.
      CONCLUSION: The review highlights the sleep disturbances in aging. We focus on
      current knowledgment in medicinal chemistry and further design of new treatments
      tools for managing sleep disturbances in aged population.

PMID- 30182853
TI  - Alzheimer's Disease-Like Pathologies and Cognitive Impairments Induced by
      Formaldehyde in Non-Human Primates.
AB  - BACKGROUND: Formaldehyde (FA) has been implicated in Alzheimer's disease (AD)
      pathology as an age-related factor and as a protein cross-linker known to
      aggregate Amyloid-Beta (Abeta) and tau protein in vitro. Higher levels of FA have
      also been found in patients with greater cognitive impairment and in AD patient
      brains. OBJECTIVE: To directly evaluate the effect of chronically elevated FA
      levels on the primate brain with respect to AD pathological markers. METHOD:
      Young rhesus macaques (5-8 yrs, without AD related mutations) were given chronic
      intracerebroventricular (i.c.v.) injections of FA or vehicle over a 12-month
      period. Monkeys were monitored for changes in cognitive ability and evaluated
      post-mortem for common AD pathological markers. RESULTS: Monkeys injected with FA
      were found to have significant spatial working memory impairments.
      Histopathological analysis revealed the presence of amyloid-beta+ neuritic-like
      plaques, neurofibrillary tangle-like formations, increased tau protein
      phosphorylation, neuronal loss and reactive gliosis in three memory (and AD)
      related brain areas (the hippocampus, entorhinal cortex and prefrontal cortex
      (PFC)) of monkeys receiving i.c.v. injections of FA. ELISA assays revealed that
      the amounts of pT181 and Abeta42 were markedly higher in the PFC and hippocampus
      of FA treated monkeys. CONCLUSION: FA was found to induce major AD-like
      pathological markers and cognitive impairments in young rhesus monkeys
      independent of genetic predispositions. This suggests FA may play a significant
      role in the initiation and progression of the disease.

PMID- 30182854
TI  - Crosstalk between Gut Microbiota and Central Nervous System: A Focus on
      Alzheimer's Disease.
AB  - The role of diet and gut microbiota in the pathophysiology of neurodegenerative
      diseases, such as Alzheimer's, has recently come under intense investigation.
      Studies suggest that human gut microbiota may contribute to the modulation of
      several neurochemical and neurometabolic pathways, through complex systems that
      interact and interconnect with the central nervous system. The brain and
      intestine form a bidirectional communication axis, or vice versa, they form an
      axis through bi-directional communication between endocrine and complex immune
      systems, involving neurotransmitters and hormones. Above all, studies suggest
      that dysbiotic and poorly diversified microbiota may interfere with the synthesis
      and secretion of neurotrophic factors, such as brain-derived neurotrophic factor,
      gammaaminobutyric acid and N-methyl D-Aspartate receptors, widely associated with
      cognitive decline and dementia. In this context, the present article provides a
      review of the literature on the role of the gutbrain axis in Alzheimer's disease.

PMID- 30182855
TI  - Microdose Lithium NP03 Diminishes Pre-Plaque Oxidative Damage and
      Neuroinflammation in a Rat Model of Alzheimer's-like Amyloidosis.
AB  - BACKGROUND: Microdose lithium is protective against Alzheimer's disease (AD),
      although the precise mechanisms through which its protective effects are
      conferred remain unclear. OBJECTIVE: To further examine the effects during the
      earliest stages of Abeta pathology, we evaluated whether NP03, a microdose
      lithium formulation, modulates Abeta-mediated oxidative damage and
      neuroinflammation when applied to a rat transgenic model of AD-like amyloidosis
      overexpressing amyloid precursor protein (APP). METHOD: McGill-R-Thy1-APP
      transgenic rats and wild-type littermates were treated with NP03 or vehicle
      formulation for 8 weeks beginning at 3 months of age - a phase preceding Abeta
      plaque deposition in the transgenic rats. RESULTS: Oxidative and nitrosative
      stress markers, protein-bound 4-hydroxynonenal (HNE) and proteinresident 3
      nitrotyrosine (3-NT), inflammatory cytokines production, as well as microglial
      recruitment towards Abeta-burdened neurons were assayed. NP03 significantly
      decreased cerebral HNE and 3-NT, and reduced production of pro-inflammatory
      cytokines in McGill-R-Thy1-APP transgenic rats. NP03 further reduced expression
      of microglia surface receptor Trem2 and led to a corresponding reduction in
      microglia recruitment towards Abeta-burdened neurons in the CA1 region of the
      hippocampus. CONCLUSION: These results suggest that NP03 may function to slow the
      AD-like pathology in part by modifying oxidative/nitrosative damage and
      neuroinflammation, raising the possibility that low doses of microencapsulated
      lithium might be of therapeutic-preventive value during very early or preclinical
      AD.

PMID- 30182856
TI  - c-Myc inhibitor 10074-G5 induces murine and human hematopoietic stem and
      progenitor cell expansion and HDR modulator Rad51 expression.
AB  - c-Myc plays a major role in the maintenance of glycolytic metabolism and
      hematopoietic stem cell (HSC) quiescence. Targeting modulators of HSC quiescence
      and metabolism could lead to HSC cell cycle entry with concomitant expansion.
      Here we show that c-Myc inhibitor 10074-G5 treatment leads to 2-fold increase in
      murine LSKCD34low HSC compartment post 7 days. In addition, c-Myc inhibition
      increases CD34+ and CD133+ human HSC number. c-Myc inhibition leads to
      downregulation of glycolytic and cyclin-dependent kinase inhibitor (CDKI) gene
      expression ex vivo and in vivo. In addition, c-Myc inhibition upregulates major
      HDR modulator Rad51 expression in hematopoietic cells. Besides, c-Myc inhibition
      does not alter proliferation kinetics of endothelial cells, fibroblasts or
      adipose derived mesenchymal stem cells, however; it limits bone marrow derived
      mesenchymal stem cell proliferation. We further demonstrate that a cocktail of c
      Myc inhibitor 10074-G5 along with tauroursodeoxycholic acid (TUDCA) and i-NOS
      inhibitor L-NIL provides a robust HSC maintenance and expansion ex vivo as
      evident by induction of all stem cell antigens analyzed. Intriguingly, the
      cocktail of c-Myc inhibitor 10074-G5, TUDCA and L-NIL improves HDR related gene
      expression. These findings provide tools to improve ex vivo HSC maintenance and
      expansion, autologous HSC transplantation and gene editing through modulation of
      HSC glycolytic and HDR pathways.

PMID- 30182857
TI  - Cordycepin downregulates Cdk-2 to interfere with cell cycle and increases
      apoptosis by generating ROS in cervical cancer cells: in vitro and in silico
      study.
AB  - Cordycepin is a small molecule from medicinal mushroom Cordyceps, which has been
      reported for anticancer properties. In this study, we investigated cordycepin
      effect on cervical cancer cells in vitro. Results indicate that treatment of
      cordycepin controlled SiHa and Hela cervical cancer cell growth, increased the
      rate of their apoptosis, and interfered with cell cycle, specifically elongated S
      phase. By using qPCR, we investigated the expression of anti-apoptotic and pro
      apoptotic proteins as well as cell cycle protein's expression in mRNA levels, and
      found there was a downregulation of cell cycle proteins CDK-2, CYCLIN-A2 and
      CYCLIN-E1 by cordycepin treatment but no significant change in pro-apoptotic or
      anti-apoptotic proteins. The intracellular reactive oxygen species (ROS) level in
      cordycepin treated cells was increased significantly, implying that apoptosis
      might be induced by ROS. Western blot analysis confirmed significant decrease of
      Cdk-2 and mild decrease of Cyclin-E1 and Cyclin-A2 by cordycepin, which might be
      responsible for regulating cell cycle. Molecular docking simulation indicated
      high binding affinity of cordycepin against Cdk-2. Molecular dynamics simulation
      further confirmed that the docked pose of cordycepin-Cdk2 complex remained within
      the binding pocket for 10ns. Thus, our study suggests that cordycepin is
      effective against cervical cancer cells, and regulating cell cycle via cell cycle
      proteins, especially downregulating Cdk-2, and inducing apoptosis by generating
      ROS are among the mechanisms of anticancer activities of cordycepin.

PMID- 30182858
TI  - Aminopyridines and acetyl-DL-leucine: new therapies in cerebellar disorders.
AB  - Cerebellar ataxia is a frequent and often disabling syndrome severely impairing
      motor functioning and quality of life. Patients suffer from reduced mobility, and
      restricted autonomy, experiencing an even lower quality of life than, e.g.,
      stroke survivors. Aminopyridines have been demonstrated viable for the
      symptomatic treatment of certain forms of cerebellar ataxia. This article will
      give an outline of the present pharmacotherapy of different cerebellar disorders.
      As a current key-therapy for the treatment of downbeat nystagmus 4-aminopyridine
      (4-AP) is suggested for the treatment of downbeat nystagmus (5-10 mg Twice a day
      [TID]), a frequent type of persisting nystagmus , due to a compromise of the
      vestibulo-cerebellum. Studies with animals have demonstrated, that a nonselective
      blockage of voltage-gated potassium channels (mainly Kv1.5) increases Purkinje
      cell (PC) excitability. In episodic ataxia type 2 (EA2), which is frequently
      caused by mutations of the PQ-calcium channel, the efficacy of 4-AP (5-10 mg TID)
      has been shown in a randomized controlled trial (RCT). 4-AP was well tolerated in
      the recommended dosages. 4-AP was also effective in elevating symptoms in
      cerebellar gait ataxia of different etiologies (2 case series). A new treatment
      option for cerebellar disease is the amino-acid acetyl-DL-leucine, which has
      significantly improved cerebellar symptoms in three case series. There are on
      going randomized controlled trials for cerebellar ataxia (acetyl-DL-leucine vs
      placebo; ALCAT), cerebellar gait disorders (SR-form of 4-AP vs placebo; FACEG)
      and EA2 (sustained-release/SR-form of 4-AP vs acetazolamide vs placebo;
      EAT2TREAT), which will provide new insights into the pharmacological treatment of
      cerebellar disorders.

PMID- 30182859
TI  - Neuroregeneration in Parkinson's Disease: From Proteins to Small Molecules.
AB  - BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative
      disorder worldwide, the lifetime risk of developing this disease is 1.5%.Motor
      diagnostic symptoms of PD are caused by degeneration of nigrostriatal dopamine
      neurons. There is no cure for PD and current therapy is limited to supportive
      care that partially alleviates disease signs and symptoms. As diagnostic symptoms
      of PD result from progressive degeneration of dopamine neurons, drugs restoring
      these neurons may significantly improve treatment of PD. METHOD: A literature
      search was performed using the PubMed, Web of Science and Scopus databases to
      discuss the progress achieved in development of neuroregenerative agents for PD.
      Papers published before early 2018 were taken into account. RESULTS: Here, we
      review several groups of potential agents capable of protecting and restoring
      dopamine neurons in cultures or animal models of PD including neurotrophic
      factors and small molecular weight compounds. CONCLUSION: Despite the promising
      results of in vitro and in vivo experiments, none of the found agents have yet
      shown conclusive neurorestorative properties in PD patients. Meanwhile, a few
      promising biologicals and small molecules have been identified. Their further
      clinical development can eventually give rise to disease-modifying drugs for PD.
      Thus, intensive research in the field is justified.

PMID- 30182860
TI  - The role of sexual networks in studies of how BV and STIs increase the risk of
      subsequent reinfection.
AB  - Prior studies have demonstrated that both bacterial vaginosis (BV) and sexually
      transmitted infections (STIs) are strong independent risk factors for subsequent
      STI. In observational studies of this biological enhancement (BE) hypothesis, it
      is important to adjust for the risk of STI exposure so that the independent
      effect of BE can be assessed. We sought to model if two markers of local sexual
      network (partner concurrency and cumulative number of STIs) represented residual
      confounding in the models of risk for subsequent infection in a study that
      screened 3620 women for STIs every 3 months for a year. Mixed-effects logistic
      regression was used to calculate the odds ratios for an incident diagnosis of
      Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis and BV
      following a diagnosis of any of these four at the prior visit, controlling for
      the cumulative number of STIs and partner concurrency variables. We found that
      partner concurrency and cumulative number of STIs were each associated with
      incident infection, and in general, controlling for these variables reduced the
      strength of the association between prior and incident infections. We conclude
      that the frequently found association between prior and incident STIs is
      associated with both BE and sexual network structure.

PMID- 30182861
TI  - Salivary and urinary metabolome analysis for pre-puberty-related biomarkers
      identification in porcine.
AB  - Estrus synchronization is important for optimal management of gilt reproduction
      in pig farms. Hormonal treatments, such as synthetic progestogens, are used on a
      routine basis, but there is a growing demand for non-hormonal alternative
      breeding tools. Before puberty, gilts exhibit a 'waiting period,' related to the
      ovarian development and gonadotrophin secretions, during which external
      stimulations, such as boar exposure, could induce and synchronize first
      ovulation. Practical non-invasive tools for identification of this period in
      farms are lacking. During this period, urinary oestrone levels are high, but
      urine sampling is difficult in group-housed females. The aim of this work was to
      search for specific biomarkers of the 'waiting period' in saliva and urine. In
      total, nine 144- to 147-day-old Large White gilts were subjected to trans
      abdominal ultrasonography three times a week for 5 weeks until puberty detection
      (week -5 to week -1 before puberty). Urine and saliva samples were collected for
      oestrone assay to detect the 'waiting period' and for metabolome analysis using
      1H-nuclear magnetic resonance spectroscopy to detect potential biomarkers of the
      'waiting period.' Gilts were slaughtered 7 days after puberty detection for
      puberty confirmation. Results were consistent with ultrasonography data for six
      gilts. Urine and saliva samples from these six gilts were analyzed. Urinary
      estrone concentration significantly increased 2 weeks before puberty detection.
      Metabolome analysis of urine samples allowed the identification of 78 spectral
      bins, among them, 42 low-molecular-weight metabolites were identified. Metabolome
      analysis of salivary samples allowed the identification of 59 spectral bins,
      among them, 23 low-molecular-weight metabolites were detected and 17 were
      identified. No potential biomarker was identified in urinary samples. In saliva,
      butyrate and 2HOvalerate, 5.79 ppm (putatively uridine), formate, malonate and
      propionate could be biomarker candidates to ascertain the pre-puberty period in
      gilt reproduction. These results confirm that non-invasive salivary samples could
      allow the identification of the physiological status of the gilts and presumably
      the optimal time for application of the boar effect. This could contribute to
      synchronize puberty onset and hence to develop non-hormonal breeding tools.

PMID- 30182862
TI  - Adaptation transculturelle en francais du Edinburgh Feeding Evaluation in
      Dementia (EdFED) Scale : un questionnaire pour evaluer les difficultes a
      s'alimenter de personnes agees presentant des troubles cognitifs en centre
      d'hebergement.
AB  - ABSTRACTThe Edinburgh Feeding Evaluation in Dementia (EdFED) Scale was designed
      to identify feeding difficulties for people with moderate to severe dementia. Its
      Canadian-French cross-cultural adaptation was carried out, as part of an
      experimental study, whose secondary objective was to document its construct
      validity. A back-translation method was followed. The EdFED-f was used during a
      meal with 26 elderly residents who had cognitive disorders. There was a
      significant correlation between EdFED-f scores and energy intakes calculated
      using a visual estimation of plate wash method (r=-0,50, p=0,009). EdFED-f scores
      also showed a significant difference according to the percentage of food consumed
      at meals (p=0,015). These results support the validity of the EdFED-f to assess
      feeding difficulties among elderly French-speaking Canadians living in
      residential and long-term care centers.

PMID- 30182863
TI  - Detection of East/Central/South African genotype Chikungunya virus during an
      outbreak in a southeastern state of Brazil.
AB  - Chikungunya virus (CHIKV) is an arbovirus transmitted by Aedes mosquitoes that
      was first identified in Brazil in 2014. It causes a febrile illness characterised
      by severe arthralgia and rash. Our group investigated a suspected CHIKV outbreak
      in Governador Valadares, state of Minas Gerais, Brazil and from 25 acute-phase
      patients, 10 had qRT-PCR positive sera samples and had E1 partial sequence
      amplified and Sanger sequenced. Samples were identified as East/Central/South
      African (ECSA) genotype by phylogenetic analysis and clustered with CHIKV
      sequences isolated in the neighbour state of Bahia. Our findings confirm previous
      predictions that ECSA genotype would spread through northeast and southeast of
      Brazil.

PMID- 30182864
TI  - Risk determinants for the development of typical haemolytic uremic syndrome in
      Belgium and proposition of a new virulence typing algorithm for Shiga toxin
      producing Escherichia coli.
AB  - In Belgium, it is mandatory to report Shiga toxin-producing Escherichia coli
      (STEC) infections to the health inspection authorities. To facilitate the
      decision making regarding infection control measures, information about the risk
      factors for the development of the haemolytic uremic syndrome (HUS) can be
      helpful. We performed statistical analyses on a dataset of 411 Belgian STEC
      strains. Demographic and clinical patient characteristics as well as phenotypical
      and genotypical STEC strain characteristics were taken into account. Multivariate
      logistic regression models indicated that age categories ?5, 6-12 and ?75; the
      stx2 gene; and the eae gene were significant HUS development risk determinants.
      The stx2a subtype had the highest risk (OR 29.6, 95% CI 7.0-125.1), while all
      stx1 subtypes encompassed a significant lower risk (OR 0.3, 95% CI 0.1-0.5).
      Presence of the stx1 gene without stx2 encompassed a lower risk than the combined
      presence of stx1 and stx2, or stx2 solely. Based on these results, we propose a
      new virulence typing algorithm that will enable the National Reference Centre to
      provide the physicians and health inspection authorities with a risk
      classification for the development of HUS. We believe this will contribute to a
      more efficient STEC infection control management in Belgium.

PMID- 30182865
TI  - Turbulence Research in the 1920s and 1930s between Mathematics, Physics, and
      Engineering.
AB  - ArgumentDuring the interwar period research on turbulence met with interest from
      different areas: in aeronautical engineering turbulence became a subject of
      experimental study in wind tunnels; in naval architecture and hydraulic
      engineering turbulence research was on the agenda because of its role for skin
      friction; applied mathematicians and theoretical physicists struggled with the
      problem to determine the onset of turbulence from the fundamental hydrodynamic
      equations; experimental physicists developed techniques to measure the velocity
      fluctuations of turbulent flows. In this paper I describe the rise of turbulence
      in the 1920s and 1930s as a research field under the label of applied mechanics.
      Although the focus is on Germany, the international development of this research
      field is illuminated by the role which Ludwig Prandtl played as its acknowledged
      "chief" (G. I. Taylor). I argue that the multifaceted character of this research
      field calls for an epistemology and historiography which intrinsically takes the
      interaction of science and engineering into account.

PMID- 30182866
TI  - How to Use a Fundamental Discovery in Physics: The Early Days of Electron
      Diffraction.
AB  - ArgumentThe discovery of electron diffraction by George Paget Thomson in Aberdeen
      and Clinton J. Davisson and Lester H. Germer at the Bell Labs has often been
      portrayed as an example of independent discovery. Neither team was particularly
      interested in the developments of the nascent quantum theory but they both ended
      up demonstrating one of the most striking experimental consequences of the new
      physics. This paper traces the aftermath of this discovery and the way electron
      diffraction immediately turned from empirical evidence of a highly novel theory
      into a technique for applied and technological research. Thomson was the first to
      design an "electron diffraction camera," an instrument that soon found its place
      in laboratories around the world. I discuss the role played by Davisson and
      Germer, and by Thomson in the development of electron diffraction as a "research
      technology," taking into account their specific institutional settings and
      research cultures. While Davisson and Germer remained in the industry-oriented
      Bell Labs, Thomson moved to Imperial College in 1930 where collaboration first,
      and competition later with George I. Finch was also relevant for the
      consolidation of an instrument that eventually became widely known as the "Finch
      Camera."

PMID- 30182867
TI  - The Interwar Period as a Machine Age: Mechanics, the Machine, Mechanisms, and the
      Market in Discourse.
AB  - ArgumentThis paper examines some of the ways that machines, mechanisms, and the
      new mechanics were treated in post-World War I discourse. Spengler's 1919 Decline
      of the West and Hessen's 1931 study of Newton have usually been tied closely to
      Weimar culture in Germany, and Soviet politics. Linking them also to the writings
      of Rathenau, Simmel, Chase, Mumford, Hayek, and others, as well as to Dada and
      film studies of the city will indicate central features of a wide-ranging,
      international discourse on the machine and mechanization. I argue that machines
      were so thoroughly integrated into social and economic experience that we can
      treat this as a distinctive new phase in the cultural history of mechanics, what
      some contemporaries called the "machine age": a period in which rather than the
      hand mill or steam engine, the city stands as an appropriate realization (and
      sometimes symbol) of the significance but also ambiguities and tensions of
      mechanical life; and concepts of mechanization were extended to encompass the
      economy and market mechanisms.

PMID- 30182868
TI  - The Shaping of Interwar Physics by Technology: The Case of Piezoelectricity.
AB  - ArgumentConcentrating on the important developments of quantum physics,
      historians have overlooked other significant forces that shaped interwar physics,
      like that of technology. Based on the case of piezoelectricity, I argue that
      interests of users of technics (i.e. devices of methods) channeled research in
      physics into particular fields and questions relevant for industrial companies
      and governmental agencies. To recognize the effects of such social forces on
      physics, one needs to study the content of the scientific activity (both
      experimental and theoretical) of the researchers within its social and
      disciplinary contexts. By examining paths of individual scientists along with a
      study of the research in the field as a whole this paper exposes a range of
      reasons that led researchers to studies pertinent to technics. In particular, it
      shows that commercial, social, and military powers shaped interwar research
      through institutions aimed at fostering technology, some of them newly founded,
      and by a general view that academic research should help technology, a position
      that became more common at the time.

PMID- 30182869
TI  - Introduction: Physics, Technology, and Technics during the Interwar Period.
AB  - Historians, philosophers, and physicists portray the 1920s and 1930s as a period
      of major theoretical breakthrough in physics, quantum mechanics, which led to the
      expansion of physics into the core of the atom and the growth and strengthening
      of the discipline. These important developments in scientific inquiry into the
      micro-world and light have turned historical attention away from other
      significant historical processes and from other equally important causes for the
      expansion of physics. World War II, on the other hand, is often seen as the
      watershed moment when physics achieved new levels of social and technical
      engagement at a truly industrial scale. Historians have shown that military
      interests and government funding have shaped physics to unprecedented degree, and
      according to some, to the extent of discontinuity with earlier practices of
      research (Forman 1987; Kevles 1990; Kaiser 2002). In this vein, Stuart Leslie
      wrote, "Nothing in the prewar experience fully prepared academic scientists and
      their institutions for the scale and scope of a wartime mobilization that would
      transform the university, industry, and the federal government and their mutual
      interrelationships" (Leslie 1993, 6). While one can never be fully ready for
      novelties, the contributors to this issue show that developments in interwar
      physics did prepare participants for their cold war interactions with industry
      and government.

PMID- 30182870
TI  - "Electron Theory" and the Emergence of Atomic Physics in Japan.
AB  - ArgumentThis paper discusses one aspect of the context in which atomic physics
      developed in Japan between 1905 and 1931. It argues that during this period,
      there was a social context in which atomic physics was valued as a study of the
      electron and was thus relevant to electrical engineering. To demonstrate this, I
      first show that after the Russo-Japanese War, electrical engineering was deemed a
      valuable and viable field of research in Japan. Second, I show that physicists
      wrote textbooks and popular accounts about the electron, covering topics from
      both atomic physics and electrical engineering and presenting the former as
      relevant to the latter. Finally, as an example of how atomic physics partially
      emerged from this context, I discuss the group of Kujirai Tsunetaro, an
      electrical engineer who worked in the physics department of the Institute for
      Physical and Chemical Research (RIKEN). From Kujirai's group, Nishina Yoshio
      started his career and became the most important Japanese atomic and nuclear
      physicist of the 1930s.

PMID- 30182871
TI  - Variation in HIV prevalence and the population-level effects of antiretroviral
      therapy in reducing tuberculosis incidence in South Africa.

PMID- 30182872
TI  - The bleeding edge.

PMID- 30182873
TI  - Unmet needs of high-risk mothers reduce success of antiretroviral treatment in
      HIV-infected infants.
AB  - In the era of effective prevention of mother-to-child transmission of HIV, the
      same psychosocioeconomic factors that predispose to mother-to-child transmission
      also substantially increase the likelihood of antiretroviral therapy failure in
      infected infants. For HIV-infected infants to benefit from early infant diagnosis
      and treatment initiation, into which much funding and effort is now invested, it
      is vital that these unmet needs of high-risk mothers are urgently attended to.
      From an ongoing study of early infant diagnosis and treatment following in utero
      transmission in KwaZulu-Natal, South Africa, we describe four cases to highlight
      these challenges facing transmitting mothers that contribute to treatment failure
      in their infants.

PMID- 30182874
TI  - Cystic fibrosis in South Africa: A changing diagnostic paradigm.
AB  - Cystic fibrosis (CF), one of the most commonly observed and diagnosed fatal
      monogenic disorders globally, was initially thought to affect individuals of
      Caucasian/European descent almost exclusively. It is increasingly appreciated,
      however, that non-Caucasian populations are also affected by this condition.
      Although this has been known in South Africa (SA) for over two decades, a large
      disparity still exists in data pertaining to the different population groups in
      the country. This article seeks to highlight existing published data on CF in SA
      populations and reflects on the means through which these have been generated
      over the years. Additionally, the article briefly discusses the consequences of
      incomplete data and how this could potentially be addressed in the future through
      innovative and collaborative approaches.

PMID- 30182875
TI  - Changes to the World Health Organization guideline on hormonal contraceptive
      eligibility for women at high risk of HIV: South African perspective and
      response.
AB  - The World Health Organization (WHO) published guidelines for hormonal
      contraceptive eligibility for women at high risk of HIV in March 2017. This
      guidance followed from a technical consultative meeting convened by the WHO in
      December 2016, where all the available evidence on hormonal contraceptives and
      risk of HIV acquisition was reviewed. This was an expert meeting with
      representation from global experts in family planning and HIV management,
      including clinicians, epidemiologists, researchers and civil society. The
      guideline development group, through a consensus, made recommendations to change
      the medical eligibility criteria for contraceptive use from category 1 to
      category 2 for progestogen-only injectable contraceptives among women at high
      risk of HIV. There was no change in the recommendation for all other methods of
      hormonal contraception. The data that informed this decision are from
      observational studies, which have limitations; therefore, causality or
      association of hormonal contraception and risk of HIV acquisition have not been
      proven. This guidance will have an impact on countries that have a high HIV
      disease burden and where progestogen-only injectable contraceptives are the
      highest used, as in South Africa (SA). The information has to be communicated in
      line with the WHO's sexual and reproductive health rights principles of ensuring
      that all women should receive evidence-based recommendations. This will empower
      them to make informed choices about their reproductive needs. This article seeks
      to clarify the decision-making process of the WHO and how the new recommendations
      were formulated. It also gives SA's response to the guidance and a perspective of
      what informed the National Department of Health's position, taking into account
      the effect this will have on SA's contraceptive guidelines.

PMID- 30182876
TI  - The National Education, Health and Allied Workers' Union (NEHAWU) strikes: South
      Africa's healthcare battlefield.
AB  - The right to strike is a fundamental right entrenched in section 23 of the Bill
      of Rights. Strikes are an almost everyday occurrence in South Africa and strikes
      in healthcare facilities raise difficult and complex moral and ethical questions.
      The right to strike is conditionally limited by section 36 of the Constitution
      and for workers engaging in essential services it is further limited under
      section 65 of the Labour Relations Act. Healthcare practitioners, including
      emergency care personnel, and much-needed healthcare facilities have come under
      attack during the National Education, Health and Allied Workers' Union (NEHAWU)
      strikes, which have prevented patients from accessing healthcare and threatened
      the training of undergraduate students and registrars. While generally security
      and policing have been lacking at targeted facilities, many doctors stood by
      their patients despite threats to their safety. Healthcare facilities, vehicles
      and practitioners must be protected. Solutions must come from politicians and
      include preventive actions and enforcement of the law.

PMID- 30182877
TI  - What should doctors and healthcare staff do when industrial action jeopardises
      the lives and health of patients?
AB  - During the recent strikes by healthcare personnel in North West Province, South
      Africa, patients were prevented from accessing emergency medical care and doctors
      and nurses were ejected from hospitals. Such conduct violates the Constitution of
      the Republic of South Africa, 1996, and is unlawful, as health services are
      'essential services' in terms of the Labour Relations Act No. 66 of 1995.
      Doctors, nurses and other healthcare personnel who are prevented from assisting
      patients by striking colleagues should take active steps to secure access to
      healthcare services for patients requiring emergency medical care.

PMID- 30182878
TI  - Starvation ketoacidosis in pregnancy presenting as euglycaemic, high anion gap
      metabolic acidosis: A case report highlighting the significance of early
      recognition and prompt intervention.
AB  - Starvation ketoacidosis (SKA) constitutes an important consideration in the
      pregnant patient who presents with profound metabolic acidosis. Pregnancy-related
      changes predispose the patient to develop SKA following relatively short periods
      (12 - 14 hours) of 'starvation'. Patients also typically look clinically well in
      relation to the significant metabolic derangements that accompany the condition.
      Prompt recognition and early institution of appropriate therapy is therefore
      extremely important in terms of optimising maternal and fetal outcome. We
      describe a pregnant patient with SKA who presented with profound euglycaemic
      ketoacidosis that resolved rapidly following the early initiation of appropriate
      therapy. Furthermore, appropriate therapy resulted in our patient avoiding the
      need for an emergency caesarean section, which is often reported in this
      scenario. The ensuing discussion addresses SKA in pregnancy, the unique features
      of our patient, and management considerations from a maternal and fetal
      perspective. We also discuss the various causes of ketoacidosis such as diabetic
      ketoacidosis (DKA), euglycaemic DKA, alcohol-induced euglycaemic ketoacidosis and
      SKA in pregnant patients.

PMID- 30182879
TI  - Oral anticoagulants and atrial fibrillation: A South African perspective.
AB  - This review evaluates the current literature on available oral anticoagulants and
      atrial fibrillation with specific relevance to the South African (SA) public
      healthcare sector, focusing on the pharmacology and monitoring of anticoagulants,
      current guidelines, initiation of treatment and risk stratification,
      effectiveness of treatment, cost-effectiveness and specific costing implications.
      The direct-acting oral anticoagulants (DOACs) are superior to warfarin, with
      dabigatran being the preferred treatment option in patients with non-valvular
      atrial fibrillation (NVAF). Warfarin is still the preferred anticoagulant in
      patients with renal failure and prosthetic heart valves and is still the most
      cost-effective anticoagulant in the SA public sector setting. There is a growing
      body of evidence that demonstrates the advantages of DOACs over warfarin in NVAF.
      Warfarin will remain the anticoagulant of choice until cheaper generic DOACs
      become available.

PMID- 30182881
TI  - Titrating insulin in patients with type 2 diabetes using a structured self
      monitoring blood glucose regimen.
AB  - BACKGROUND: Self-monitoring of blood glucose (SMBG) can inform on the timing of
      hyperglycaemia, but there is currently no standardised approach to utilising
      these data to improve glycaemic control in patients with type 2 diabetes.
      OBJECTIVES: To assess the improvement in glycaemic control when an insulin
      titration algorithm was used in combination with SMBG in patients with poorly
      controlled, insulin-treated type 2 diabetes. METHODS: This 6-month prospective
      study recruited 39 poorly controlled (glycated haemoglobin (HbA1c) >=8.5%; 69.4
      mmol/mol) type 2 diabetes subjects using twice-daily biphasic insulin from two
      state hospitals in Tshwane, South Africa. Patients were asked to perform
      structured SMBG over 4 weeks and return monthly for consultations where
      physicians titrated insulin doses using an algorithm guided by the data
      collected. The primary endpoint was the trend in HbA1c measured at baseline and 3
      and 6 months. RESULTS: Mean HbA1c decreased over the study period by 1.89% (95%
      confidence interval (CI) -2.46 - -1.33; p<0.001). The hypoglycaemic event rate
      (<4.0 mmol/L) was 33.08 events per patient year. Total daily insulin use
      increased by a mean of 40.12 units over the study period (standard error 7.7;
      p<0.001) and weight increased by an average of 3.98 kg (95% CI 2.56 - 5.41;
      p<0.001). CONCLUSIONS: Monthly algorithmic insulin titration guided by structured
      SMBG can markedly improve glycaemic control in patients with type 2 diabetes by
      aggressively increasing insulin doses not previously expected in this population,
      with moderate hypoglycaemic events and weight gain observed.

PMID- 30182880
TI  - Congenital disorders in South Africa: A review of Child Healthcare Problem
      Identification Programme (Child PIP) mortality data, 2005 - 2017.
AB  - BACKGROUND: Congenital disorders (CDs) form a major challenge for those affected,
      and for the structuring of services around their health needs. In South Africa
      (SA) the size and nature of the problem are unknown because reporting of CDs has
      been unreliable. OBJECTIVES: To ascertain the occurrence and spectrum of
      congenital disorders in children dying in SA hospitals participating in the Child
      Healthcare Problem Identification Programme (Child PIP). METHODS: Child PIP has
      been used for auditing in-hospital childhood deaths in children's wards in SA
      state hospitals since 2005. By 2017, over 60 000 audited deaths had been entered
      into the Child PIP database. We searched this database for CD occurrence and
      spectrum. RESULTS: The number of deaths where a CD diagnosis was given as the
      Main Cause of Death was 243, 0.4% of all-cause mortality. In 1 678 deaths, CDs
      were assigned as an Underlying Condition, a 2.8% occurrence. A diagnosis of CD
      was assigned 1 968 times, indicating an overall CD burden in the children who
      died of 3.2%, many children having more than one CD diagnosis. The spectrum of
      CDs was wide, with CDs of the heart being most prominent. CONCLUSIONS: These new
      data paint a broad picture of the CD challenge that confronts the SA health
      system, a challenge that will increase in importance with the current decline in
      infectious diseases.

PMID- 30182882
TI  - Emergency intubation in trauma in KwaZulu-Natal Province, South Africa.
AB  - BACKGROUND: Advanced airway management is a research priority in prehospital
      care. There is a high burden of major trauma in KwaZulu-Natal (KZN) Province,
      South Africa (SA), and transfer times to trauma units are often prolonged.
      OBJECTIVES: To examine emergency intubation practice in trauma and burns patients
      in Pietermaritzburg, KZN, and its environs. METHODS: This was a prospective
      consecutive case series, conducted from 11 May to 17 July 2016. Data were
      collected from urban emergency department (ED), rural hospital and roadside
      procedures in Pietermaritzburg and its drainage area. Patients with emergency
      intubation following trauma were eligible for inclusion. The primary outcome was
      successful airway management. Secondary outcomes included first-pass success and
      adverse events. RESULTS: Forty-one cases were recorded in patients aged 1 - 60
      years. No instances of unsuccessful airway management were reported. Recorded
      first-pass intubation success rates were higher in receiving EDs than rural
      hospitals (19/22 v. 2/7; p=0.003). Use of a formal preintubation checklist was
      associated with a higher first-pass success rate (21/23 v. 6/15; p=0.001) and
      fewer adverse events (0/23 v. 7/16; p<0.001). Identified adverse event rates were
      1/22 (EDs), 5/8 (rural hospitals) and 2/9 (roadside). Unmedicated intubation was
      more common in rural hospitals than EDs (3/8 v. 1/22; p=0.019), despite absence
      of cardiac arrest in these cases. Minimum standards of anaesthetic monitoring
      were not consistently met in any setting. CONCLUSIONS: The use of a preprocedural
      checklist was associated with improved intubation outcomes and may improve
      practice in SA trauma care and the prehospital environment, including in rural
      hospitals. Standardised rapid sequence induction protocols, routine use of
      introducers and end-tidal carbon dioxide monitoring, and increased availability
      of intraosseous devices also merit consideration. Key performance indicators
      should be monitored routinely.

PMID- 30182883
TI  - Posterior urethral valves in South African boys: Outcomes and challenges.
AB  - BACKGROUND: Posterior urethral valves (PUV) are a common cause of congenital
      obstructive nephropathy. The outcome of patients with PUV at Chris Hani
      Baragwanath Academic Hospital in Johannesburg, South Africa, has not been
      documented previously. OBJECTIVES: To describe the outcome of patients diagnosed
      with PUV over a 29-year period from January 1985 to December 2013, and to analyse
      risk factors for chronic kidney disease. METHODS: This was a retrospective record
      review of boys aged <14 years diagnosed with PUV at Chris Hani Baragwanath
      Academic Hospital. PUV was diagnosed by a voiding cystourethrogram (VCUG) and/or
      at cystoscopy. Valves were resected primarily or after vesicostomy. The
      glomerular filtration rate was calculated using the Schwartz formula, and
      stratified as normal or decreased for age at presentation and at the final visit.
      RESULTS: Records of 181 patients were analysed. The diagnosis was made during the
      first year of life in 139 patients (76.8%). Clinical presentation included
      urinary tract infection (UTI) in 109 patients (60.2%), palpable bladder in 98
      (54.1%), palpable kidney in 85 (46.9%), and poor urinary stream in 78 (43.1%). An
      ultrasound scan was reported normal in 10.9%. Vesicostomy was performed in 80
      patients (44.2%) and primary valve ablation in 101 (55.8%), with vesicostomy
      being more prevalent in the pre-2000 era. The median duration of follow-up was 21
      months (interquartile range 5 - 79) and renal outcome at last visit was normal in
      117 patients (64.6%). The presence of bladder diverticula was associated with a
      favourable renal outcome. Thirteen patients (7.2%) died, and 102 (56.3%)
      defaulted from follow-up. CONCLUSIONS: PUV frequently presents with UTI and
      palpable bladder and/or kidneys. Findings on ultrasound were normal in 10.9% of
      our patients with PUV. A VCUG is indicated in the presence of palpable kidneys or
      bladder even if the ultrasound scan is normal. Bladder diverticula as a pressure
      release mechanism are renoprotective. Vesicostomy or primary valve ablation did
      not affect final renal outcome. Chronic kidney disease occurred in 34.8% of
      patients after surgical correction. Adherence to scheduled appointments is
      problematic in this population. Long-term follow-up is mandatory.

PMID- 30182884
TI  - The presentation, management and outcomes of Fournier's gangrene at a tertiary
      urology referral centre in South Africa.
AB  - BACKGROUND: Fournier's gangrene (FG) is a clinically relevant condition with a
      high mortality rate. In South Africa (SA) most affected patients present at
      district and regional level hospitals. It is important for doctors to recognise
      the condition and accurately assess patients with FG to decide which of them need
      urgent referral to a tertiary centre. OBJECTIVES: To review the presentation,
      management and outcomes of patients with FG at a tertiary urology referral
      centre, with the specific intention of identifying prognostic factors and
      assessing the validity of the Fournier's Gangrene Severity Index (FGSI). METHODS:
      A retrospective chart review was performed of all patients treated for FG over a
      5-year period at Grey's Hospital in Pietermaritzburg, SA. HIV-positive patients
      were compared with patients with diabetes mellitus (DM). The FGSI was calculated
      for each patient. Regression analysis was performed to identify risk factors.
      RESULTS: Forty-four patients (mean age 51 years) were treated for FG,
      corresponding to 8.8 patients per year. HIV was the commonest comorbidity,
      followed by DM. HIV-positive patients presented at a younger age than non-HIV
      positive patients (p<0.001). On average the patients underwent 1.33 debridements,
      and 45.5% required transfusion. All were treated with broad-spectrum antibiotics.
      The overall mortality rate was 11.4% and the mean hospital length of stay was 26
      days. There was no difference between the mean age of survivors and non-survivors
      (p=0.752). There was no association between mortality, HIV, DM or number of
      debridements. The mean (standard deviation) FGSI was significantly different in
      patients who died (15.4 (4.78)) and those who survived (5.92 (4.09)) (p<0.001).
      There was a significant association between FGSI >9 and mortality (p=0.017). FGSI
      >9 predicted 44.4% mortality, and FGSI <=9 predicted 95.5% survival. A
      combination of FGSI >9, debridement outside the perineum (onto the abdominal
      wall, chest or limbs) and requirement for organ support was present in 80.0% of
      patients who died and was a significant risk factor for mortality (p=0.002).
      CONCLUSIONS: In a resource-constrained environment such as SA, outcome prediction
      is necessary to enable resource allocation. Patients with an FGSI >9 have a high
      risk of mortality and will benefit from ICU care. The combination of FGSI >9,
      requirement for organ support and extension beyond the perineum is associated
      with a very high risk of mortality and may be useful as an exclusion criterion
      when allocating scarce resources.

PMID- 30182885
TI  - What do South African adolescents want in a sexual health service? Evidence from
      the South African Studies on HIV in Adolescents (SASHA) project.
AB  - BACKGROUND: Young people in sub-Saharan Africa (SSA) are disproportionately
      affected by HIV, sexually transmitted infections and unplanned pregnancies. The
      provision of accessible sexual and reproductive health services (SRHS) for young
      people in SSA is vital to reduce this burden. OBJECTIVES: To examine the needs of
      South African (SA) adolescents with regard to differentiated, accessible and
      adolescent-responsive SRHS. METHODS: Data were drawn from a larger project
      examining the feasibility of conducting HIV vaccine trials in adolescents.
      Fifteen focus group discussions were conducted across five research sites in four
      SA provinces with 120 male and female adolescent human papillomavirus vaccine
      trial participants aged 12 - 19 years from low-income areas with a high incidence
      of HIV. Transcribed data were double-coded using framework analysis. RESULTS:
      Three main themes emerged on how best to improve SRHS for adolescents in resource
      limited settings: adolescent-friendly services, availability of developmentally
      appropriate and tailored information, and improved relationships between
      healthcare workers and clinic attendees. Participants wanted more flexible
      opening hours at SRHS to account for travel time to clinics from school and home.
      They suggested that services include contraception, counselling, educational
      materials, links to adoption services, emergency vehicles, pre- and postnatal
      care, and improved service quality from clinic staff. CONCLUSIONS: While
      dedicated adolescent SRHS might best meet the needs of young people in SA, the
      study suggests that failing this, existing SRHS should be more responsive to
      adolescent use. Innovations such as mobile outreach services, self-testing and
      flexible hours will help SRHS respond to adolescents' needs.

PMID- 30182886
TI  - 'You can talk about condoms [with younger men] while older men ... beat you for
      that': Young women's perceptions of gender-based violence within
      intergenerational relationships in South Africa.
AB  - BACKGROUND: In South Africa (SA), HIV prevalence is significantly higher in young
      women than in young men. Intergenerational relationships and women's dependence
      on men are known HIV risks. OBJECTIVES: To qualitatively explore young women's
      perceptions and experiences of dating younger and older men and their perceived
      risks for gender-based violence. METHODS: From July to September 2011, we
      conducted eight focus group discussions (FGDs) and 20 in-depth interviews (IDIs)
      with young women aged 15 - 24 years. Women were recruited from two SA
      communities: one urban location in Gauteng Province and one rural location in
      Limpopo Province. All interviews were recorded, transcribed and translated from
      local languages into English. The study team then analysed the transcripts
      thematically, using an inductive approach, with ATLAS-ti (v6.2) software.
      RESULTS: In total, 110 young women participated, 20 of them in both the FGDs and
      the IDIs. Young men were viewed by the participants as immature, unable to
      provide financially and likely to be HIV-positive, although young women sought
      out young men for 'love', mutual understanding and intimacy. In contrast, older
      men were perceived as easy to respect, ready for marriage and able to provide for
      women's needs. Young women sought older men as providers, but acknowledged that
      older men were more likely to be violent and that discussing sexual and
      reproductive health and HIV with them was difficult. Young women expressed the
      belief that if a man was providing for them financially, he had 'the right' to
      use violence. CONCLUSIONS: The interviews highlighted young women's mixed views
      on the 'value' of older v. younger partners, and the perceived and real risks of
      violence in intergenerational relationships. There is a need for interventions
      addressing power dynamics in relationships, including healthy communication.
      However, to address young women's vulnerability to violence, ultimately young
      women and their families need access to economic opportunities that reduce
      dependence on transactional relationships.

PMID- 30182887
TI  - In the aftermath of a suicide: Any lessons from the sorrow?

PMID- 30182888
TI  - The Cape Town Declaration on Access to Cardiac Surgery in the Developing World.
AB  - Twelve years after cardiologists and cardiac surgeons from all over the world
      issued the 'Drakensberg Declaration on the Control of Rheumatic Fever and
      Rheumatic Heart Disease in Africa', calling on the world community to address the
      prevention and treatment of rheumatic heart disease (RHD) through improving
      living conditions, to develop pilot programmes at selected sites for control of
      rheumatic fever and RHD, and to periodically review progress made and challenges
      that remain, RHD still accounts for a major proportion of cardiovascular diseases
      in children and young adults in low- and middle-income countries, where more than
      80% of the world population live. Globally equal in prevalence to human
      immunodeficiency virus infection, RHD affects 33 million people worldwide.
      Prevention efforts have been important but have failed to eradicate the disease.
      At the present time, the only effective treatment for symptomatic RHD is open
      heart surgery, yet that life-saving cardiac surgery is woefully absent in many
      endemic regions. In this declaration, we propose a framework structure to create
      a co-ordinated and transparent international alliance to address this inequality.

PMID- 30182889
TI  - Medical students' perceptions on euthanasia and physician-assisted suicide: Are
      they fully informed?

PMID- 30182890
TI  - To persuade or to inform?

PMID- 30182891
TI  - Severe hypercholesterolaemia with a high risk of atherosclerosis may be
      precipitated by a high-sterol diet.

PMID- 30182892
TI  - Paediatric hypertension in South Africa: An underestimated problem calling for
      action.

PMID- 30182893
TI  - Minimum inhibitory concentration-guided antimicrobial therapy - the Achilles heel
      in the antimicrobial stewardship agenda.
AB  - The global problem of resistance to antimicrobials has resulted in a co-ordinated
      drive to use antimicrobial agents more responsibly. At a clinical level this is
      promoted through antimicrobial stewardship which demands appropriate use through
      optimal drug selection. Many factors play a role in this process of selection,
      antimicrobial susceptibility and the pharmacodynamics of the drug being two key
      determinants. Yet the detail provided by current diagnostic antimicrobial
      susceptibility testing is suboptimal and does not allow for adequate dose
      optimisation. The minimum inhibitory concentration (MIC) which underlies all
      antimicrobial susceptibility testing is largely ignored in the decision-making
      process of optimal drug selection. Understanding and application of MIC-guided
      antimicrobial therapy is desperately needed if antimicrobial stewardship is to
      truly fulfil its mandate.

PMID- 30182894
TI  - Termination of pregnancy: Cultural practices, the Choice on Termination of
      Pregnancy Act and the constitutional rights of children.
AB  - The cultural practice of ukuthwala, the abduction for marriage of young girls,
      violates their constitutional rights and contravenes the Children's and Sexual
      Offences Act. The provisions of the Choice Act for the third trimester of
      pregnancy are more onerous than the former Abortion Act and violate the
      constitutional rights of girls and women who face a serious threat to their
      physical or mental health or have been raped or subjected to incest. The Choice
      Act should be amended accordingly. Until it is amended, healthcare practitioners
      should use the constitutional 'best interests of the child' principle as
      interpreted by the Children's Act when deciding whether or not to terminate the
      pregnancy of a child in the third trimester.

PMID- 30182895
TI  - We are tired of 'adrenal fatigue'.
AB  - There are numerous articles in the lay press discussing the existence and under
      diagnosis of adrenal fatigue. Proponents of adrenal fatigue state that millions
      of people have under-active adrenal glands due to repeated stressors, resulting
      in numerous nonspecific symptoms such as fatigue, insomnia, joint pain and weight
      gain, among others. In studies to date, proposed methods to assess adrenal
      fatigue have produced conflicting results and the methodology for assessing the
      hypothalamic-pituitary-adrenal (HPA) axis has often been inappropriate.
      Furthermore, only a minority of studies have actually examined the HPA axis.
      Current evidence does not support the existence of adrenal fatigue or the
      usefulness of supplements to support adrenal function.

PMID- 30182896
TI  - Complete resolution of apparently definite radiological and histological usual
      interstitial pneumonia.
AB  - Idiopathic pulmonary fibrosis is considered to be the most common form of
      pulmonary fibrosis. It is a progressive and irreversible disease with a reported
      median survival of ~3 years. The pathological correlate is usual interstitial
      pneumonia (UIP), and although antifibrotic agents can slow down lung function
      decline, they do not completely reverse the disease process. To date, there have
      been no case reports describing reversal of UIP. We present a case where both the
      imaging and histology were compatible with definite UIP, yet it reversed with
      immunosuppressive therapy without the use of antifibrotic agents.

PMID- 30182897
TI  - Leveraging the Road to Health booklet as a unique patient identifier to monitor
      the prevention of mother-to-child transmission programme.
AB  - BACKGROUND: Currently there is no unique patient identification system in the
      South African public health sector. Therefore, routine laboratory data cannot
      effectively be de-duplicated, thereby hampering surveillance of laboratory
      diagnosed diseases such as mother-to-child transmission of HIV. OBJECTIVES: To
      determine the uptake of Road to Health booklet (RTHB) identifiers at HIV
      polymerase chain reaction (PCR) birth test and describe their performance in
      linking follow-up test results in the early infant diagnosis programme. METHODS:
      Between May 2016 and May 2017, Tshwane District Clinical Services implemented a
      unique patient identifier pilot project in which a sticker-page of unique,
      readable, barcoded patient identifiers was incorporated in the patient-retained
      immunisation record (the RTHB) before distribution. Uptake of RTHB identifiers at
      birth was calculated as the proportion of HIV PCR tests in infants aged <6 days
      registered with an RTHB identifier over the total number of registered HIV PCR
      tests. Descriptive analysis of demographic details was performed among infants
      with two registered HIV PCR tests linked by the RTHB identifier, and performance
      of the National Health Laboratory Service Corporate Data Warehouse (NHLS CDW)
      linking algorithm in matching RTHB-linked results was calculated using a 2 * 2
      table. RESULTS: A total of 5 309 HIV PCR birth tests registered with an RTHB
      identifier were extracted from the NHLS CDW over the 13-month period of the pilot
      project. The number of registered RTHB identifiers increased from 24 (2% of birth
      PCR tests) in May 2016, peaking at 728 (56% of birth PCR tests) in May 2017.
      Among infants with a registered RTHB identifier at birth, 635 (12%) had a
      subsequent linked HIV PCR test, as indicated by the same RTHB number registered
      for a later specimen. Demographic details at the time of birth and subsequent PCR
      test were compared, demonstrating that <4% of infants had exact matches for name,
      surname, date of birth and sex; 74% of birth tests had variations such as 'born
      to' or 'baby of ' in place of a first name; surnames matched exactly in 61% of
      cases; 18% (n=116) of infants had both tests performed at the same facility, of
      which only 27% (n=31) had the same patient folder number on both test results.
      CONCLUSIONS: Leveraging RTHBs as unique patient identifiers, even if used
      temporarily until linkage to other future national unique identifiers, promises
      to be an effective scalable approach to laboratory-based surveillance,
      facilitating healthcare provider access to all test results from birth.

PMID- 30182898
TI  - The unmet needs and health priorities of the urban poor: Generating the evidence
      base for urban community health worker programmes in South Africa.
AB  - BACKGROUND: There is a growing interest in involving community health workers
      (CHWs) into the formal healthcare system in South Africa (SA). OBJECTIVES: To
      generate evidence for defining CHW tasks in urban SA. METHODS: A cross-sectional
      survey of residents of Diepsloot, northern Johannesburg, was performed using
      geographically weighted random sampling, with home-based health assessment and a
      questionnaire on sociodemographics, medical history, experience of violence,
      health-seeking behaviour and perceived health priorities. RESULTS: Between May
      2013 and March 2014, 1 230 adults participated. Self-reported medical conditions
      included hypertension (12%), HIV (10%), diabetes (3%), cancer (1%) and mental
      illness (1%). Health assessments identified a high prevalence of undiagnosed
      conditions: hypertension (26%), obesity or overweight (46%), mild to severe
      depression (23%), HIV infection (5.8%) and tuberculosis (TB) (0.4%). Among women,
      18% had unmet family planning needs and 77% had never had a Pap smear. Sexually
      transmitted infection symptoms were reported by 7% of participants. Physical
      violence was widespread, with 13% having experienced and 16% witnessing violence
      in the past year, with women mostly experiencing violence at home and men in the
      community. Participants' top health concerns were crime, safety and violence
      (49%) and HIV (18%); healthy living/weight control was listed by only 8% of
      participants. CONCLUSIONS: Alignment of CHW roles to unmet health needs and
      perceived health priorities will be important for optimal impact of CHW
      programmes in urban communities. Our data suggest that the CHW role should expand
      from a traditional focus on HIV, TB and maternal health to include non
      communicable diseases, healthy lifestyle, and the intersection of violence and
      health.

PMID- 30182899
TI  - Compulsory community service for doctors in South Africa: A 15-year review.
AB  - BACKGROUND: Compulsory community service (CS) for health professionals for 12
      months was introduced in South Africa (SA) in 1998, starting with medical
      practitioners. Up to 2014, a total of 17 413 newly qualified doctors and ~44 000
      health professionals had completed their year of service in public health
      facilities around the country. While a number of studies have described the
      experience and effects of CS qualitatively, none has looked at the programme
      longitudinally. OBJECTIVES: To describe the findings and analyse trends from
      surveys of CS doctors between 2000 and 2014, specifically with regard to their
      distribution, support, feedback and career plans. METHODS: A consecutive cross
      sectional descriptive study design was used based on annual national surveys of
      CS doctors. The study population of between 1 000 and 1 300 each year was
      surveyed with regard to their origins, allocations, experiences of the year and
      future career plans. RESULTS: The total study population varied between 1 057 and
      1 308 each year, with response rates of 20 - 77%. The average turn-up rate of 89%
      showed a decreasing tendency, while 77% of respondents were satisfied with the
      allocation process. Over the 15-year period, the proportion of CS doctors who
      were black and received a study bursary, and who were allocated to rural areas
      and district hospitals, increased. The great majority believed that they had made
      a difference (91%) and developed professionally (81%) over the course of the
      year, but only about half felt adequately supported clinically and
      administratively. The attitude towards CS of the majority of respondents shifted
      significantly from neutral to positive over the course of the 15 years. In terms
      of future career plans, 50% hoped to specialise, a decreasing minority to go
      overseas or into private practice, and a constant 15% to work in rural or
      underserved areas. CONCLUSIONS: This study is the first to track the experience
      of compulsory CS over time in any country in order to describe the trends once it
      had become institutionalised. The SA experience of CS for doctors over the first
      15 years appears to have been a successively positive one, and it has largely met
      its original objectives of redistribution of health professionals and
      professional development. Greater attention needs to be given to orientation,
      management support and clinical supervision, and focusing professional
      development opportunities on the important minority who are prepared to stay on
      longer than their obligatory year. CS still needs to be complemented by other
      interventions to capitalise on its potential.

PMID- 30182900
TI  - Obstetrics knowledge and skills training as a catalyst for change.
AB  - BACKGROUND: Poor emergency obstetric care has been shown by national confidential
      enquiries into maternal deaths to contribute to a number of maternal deaths in
      South Africa. OBJECTIVES: To assess whether a structured training course can
      improve knowledge and skills and whether this can influence the capacity of a
      healthcare facility to provide basic and comprehensive emergency obstetric care
      signal functions. METHODS: A baseline survey was conducted to assess the seven
      basic emergency obstetric and neonatal care signal functions in 51 community
      health centres (CHCs) and the nine comprehensive emergency care signal functions
      in 62 district hospitals (DHs). A re-assessment was conducted 1 year after
      saturation training had been provided in each district. The delegates were
      trained using a structured training programme (Essential Steps in Managing
      Obstetric Emergencies, ESMOE) and their knowledge and skills were tested before
      and after the training. Saturation training was considered to have been achieved
      once 80% of the healthcare professionals involved in maternity care had been
      trained. RESULTS: There was a significant improvement in the knowledge and skills
      of doctors, namely by 16.8% and 32.8%, respectively, of advanced midwives by
      13.7% and 29.0%, and of professional nurses with midwifery by 16.1% and 31.2%.
      The seven basic emergency care functions improved from 60.8% to 67.8% in the CHCs
      and from 90.7% to 92.5% in the DHs before and after training. If the two signal
      functions that are not within the scope of practice of professional nurses with
      midwifery are excluded (viz. assisted delivery and manual vacuum aspiration), the
      functionality of CHCs increased from 85.1% to 94.9%. CONCLUSIONS: The ESMOE
      training programme improved knowledge and skills, but there was a modest
      improvement in the functionality of the facilities. Improvement in functionality
      requires changes in the structure of the health system, including changing the
      scope of practice of professional nurses with midwifery and employing more
      advanced midwives in CHCs.

PMID- 30182901
TI  - Infant feeding practices in Soweto, South Africa: Implications for healthcare
      providers.
AB  - BACKGROUND: The 2011 Tshwane Declaration for the Promotion of Breastfeeding in
      South Africa ended the country's longstanding support for promoting either
      exclusive breastfeeding (EBF) or exclusive formula feeding for HIV-positive
      mothers. However, South Africa's EBF rate is only 32%. OBJECTIVES: To describe
      multilevel factors associated with different infant feeding practices among HIV
      positive and negative mothers of infants aged <6 months in an HIV-endemic
      community. METHODS: A cross-sectional survey was administered to 298 HIV-positive
      and negative mothers accessing care in one of five community health clinics in
      Soweto, Johannesburg, between September 2015 and May 2016. Infant feeding
      practices and associated factors were explored through descriptive and
      multivariate analysis. RESULTS: Excluding HIV-positive mothers who chose formula
      feeding (n=97), breastfeeding initiation was almost universal (99.5%). Caesarean
      section (CS) was the most common reason mothers delayed breastfeeding. HIV
      positive mothers were significantly more likely to report prolonged EBF (and
      formula feeding) practices than their HIV-negative counterparts. Breastfeeding
      mothers were significantly more likely to be unemployed than mothers who formula
      fed. Mixed feeding was common. CONCLUSIONS: EBF remains strongly associated with
      HIV status as opposed to infant health and development. Breastfeeding support for
      working mothers is needed. While breastfeeding increased following the
      Declaration, more should be done in the health setting to communicate the risks
      of mixed feeding in the first 6 months. The high rate of CSs reported by mothers,
      linked to late initiation of breastfeeding, also needs the medical community's
      attention.

PMID- 30182902
TI  - Antibiotic use and resistance: Knowledge, attitudes and perceptions among primary
      care prescribers in South Africa.
AB  - BACKGROUND: Antibiotic resistance (ABR) is a major threat to global health,
      driven in part by inappropriate prescription of antibiotics in primary care.
      OBJECTIVES: To describe South African (SA) prescribers' knowledge of, attitudes
      to and perceptions of ABR. METHODS: We conducted a cross-sectional survey of
      knowledge of, attitudes to and perceptions of ABR among a convenience sample of
      primary healthcare providers in SA, the majority from the private sector. We used
      logistic regression to examine associations between knowledge and prescribing
      behaviours. RESULTS: Of 264 prescriber respondents, 95.8% (230/240) believed that
      ABR is a significant problem in SA and 66.5% (157/236) felt pressure from
      patients to prescribe antibiotics. The median knowledge score was 5/7, and scores
      were highest in respondents aged <55 years (p=0.0001). Prescribers with higher
      knowledge scores were more likely than those with lower scores to believe that to
      decrease ABR, narrow-spectrum antibiotics should be used (adjusted odds ratio
      (aOR) 1.29, 95% confidence interval (CI) 1 - 1.65) and more likely to report that
      explaining disease features that should prompt follow-up was a useful alternative
      to prescribing (aOR 1.47, 95% CI 1.058 - 2.04), and were less likely to report
      that antibiotics cannot harm the patient if they are not needed, so they
      prescribe when not necessary (aOR 0.57, 95% CI 0.38 - 0.84). CONCLUSIONS:
      Prescribers of antibiotics in the private sector in SA were aware of the problem
      of ABR, but felt pressure from patients to prescribe. Those with higher knowledge
      scores reported positive prescribing behaviours, suggesting that more education
      is needed to tackle the problem of ABR.

PMID- 30182903
TI  - Pregnancy outcome in patients with pregestational and gestational diabetes
      attending Groote Schuur Hospital, Cape Town, South Africa.
AB  - BACKGROUND: The burden of diabetes mellitus (DM) has increased dramatically
      worldwide. The association between poorly controlled DM and poor pregnancy
      outcomes has been well described. OBJECTIVES: To describe the pregnancy outcomes
      of patients with pregestational and gestational DM attending Groote Schuur
      Hospital, Cape Town, South Africa. METHODS: A retrospective audit was undertaken
      of all women with pregestational and gestational DM (GDM) who attended Groote
      Schuur Hospital obstetric care from 1 September 2010 to 31 August 2011.
      Information routinely collected at booking and during the rest of pregnancy was
      entered onto a data abstraction form. Patients diagnosed with GDM were further
      subdivided into two groups, GDM and impaired glucose tolerance (IGT), depending
      on the oral glucose tolerance test results. RESULTS: A total of 725 diabetic
      pregnancies were managed: 35 women had type 1 DM (T1DM), 194 had type 2 DM
      (T2DM), 192 had GDM and 304 had IGT. The median glycated haemoglobin (HbA1c)
      value at booking was highest for T1DM, followed by T2DM and lastly GDM. Overall,
      10.7% of women had pre-existing hypertension and 9.8% developed pre-eclampsia
      (PET). The preterm delivery rate (before 38 weeks) was 68.8% for women with T1DM,
      38.7% for those with T2DM, 34.9% for those with GDM and 22.4% for those with IGT.
      The caesarean section rate exceeded 50% in all groups. The overall perinatal
      mortality rate was 2.5% (25/1 000 births) for the study population, with T1DM and
      T2DM contributing most deaths (6.4% and 4.2%). The overall rate of congenital
      malformations was 2.4% (n=18 cases), but the rate was 5.7% for patients with T1DM
      and 4.6% for those with T2DM. CONCLUSION: The audit demonstrated outcomes similar
      to those in the developed world, with major congenital malformations, unexplained
      stillbirths and PET accounting for the majority of perinatal deaths. Stricter
      control with the aim of achieving lower or normal HbA1c levels before conception
      may be the only intervention that could bring about change.

PMID- 30182904
TI  - Clinical and pathological features of acral melanoma in a South African
      population: A retrospective study.
AB  - BACKGROUND: Acral melanoma (AM) is a rare subtype of cutaneous melanoma (CM) that
      disproportionately affects skin of colour and carries a poorer prognosis than
      other melanoma subtypes. The poor prognosis is attributed to late diagnosis and
      subsequent relatively high Breslow thickness, but also to an intrinsic biological
      aggressiveness. Scientific data on AM from the developing world are limited and a
      need exists to characterise the disease further in the South African (SA)
      population. OBJECTIVES: To describe the clinical and pathological features of AM
      in an SA population. METHODOLOGY: A retrospective chart review characterised the
      demographics, clinical features and histological data of 66 patients diagnosed
      with AM between January 2010 and June 2016 at Tygerberg Academic Hospital, Cape
      Town, SA. RESULTS: Sixty-six patients with AM were identified from 335 patients
      diagnosed with CM during the set time frame. The mean age (standard deviation
      (SD)) was 61.5 (12.5) years. Forty-two (63.6%) of the patients were female
      (male/female ratio 1:1.75). The majority of patients diagnosed with AM were black
      (48.5%), and the proportion of AM in black patients with CM was 80.0%. Fifty-six
      AMs (84.8%) were located on the foot and 10 (15.2%) on the hand. The median
      duration of the lesion before diagnosis was 10 months (range 2 - 84) and the mean
      (SD) tumour size was 3.8 (2.2) cm at diagnosis. The mean Breslow thickness of all
      AMs at diagnosis was 5.2 mm (median 4.2  mm, range 0 - 22). Stage of disease was
      known in 41 patients, 23 (56.1%) of whom had at least stage III disease at
      diagnosis. Mean Breslow thickness for foot and hand melanomas was 4.9 mm (range 0
      - 22) and 6.9 mm (range 0 - 13.3), respectively (p=0.2552). The mean Breslow
      thickness in the black population was 6.3 mm compared with 4.2 mm and 4.3 mm,
      respectively, in the white and coloured populations (p=0.178). Patients from
      outside the Western Cape Province (WC) presented with a mean Breslow thickness of
      6.6 mm (range 0 - 14.5) and patients from the WC with a mean Breslow thickness of
      4.9 mm (range 0 - 22) (p=0.3602). CONCLUSIONS: AMs accounted for a significant
      proportion of all CMs diagnosed. Patients presented with an advanced stage of
      disease at diagnosis, and further studies are needed to further investigate the
      reasons for delayed diagnosis.

PMID- 30182905
TI  - Alcohol marketing and adolescent alcohol consumption: Results from the
      International Alcohol Control study (South Africa).
AB  - BACKGROUND: A complete ban on alcohol advertisements has been proposed for South
      Africa (SA), but there has been limited local research on the association between
      exposure to alcohol advertisements and alcohol consumption. OBJECTIVES: To
      examine the role of demographic factors, exposure to alcohol marketing and liking
      of alcohol advertisements in predicting use of alcohol in the past 6 months among
      older adolescents in Tshwane, Gauteng Province, SA. METHODS: Participants
      comprised the adolescent sub-sample (N=869) of the International Alcohol Control
      study survey that was conducted in SA. They consisted of 408 males and 461
      females aged 16 and 17 years who took part in structured interviews on their
      alcohol consumption and various alcohol-related attitudes and behaviours. A
      multiple survey logistic regression analysis of the dependent variable alcohol
      use in the past 6 months on the independent variables age, gender, educational
      status, socioeconomic status, exposure to alcohol brand marketing and liking of
      alcohol advertisements was used. Odds ratios (ORs) and 95% confidence intervals
      (CIs) were estimated. RESULTS: The prevalence of drinking in the past 6 months
      was 10.6% (95% CI 5.9 - 18.3). The number of modes of alcohol brand/product
      advertising to which the adolescents were exposed was positively associated with
      alcohol use in the past 6 months. An additional mode of alcohol brand/product
      advertising exposure led to a relative increase of 1.13 (95% CI 1.01 - 1.28) in
      the odds of alcohol use in the past 6 months (e.g. a participant who was exposed
      to advertisements via seven different channels was 2.08 times more likely to have
      used alcohol in the past 6 months than a participant with exposure via a single
      channel). Having a strong dislike of alcohol advertisements was associated
      negatively (protective) with alcohol use in the past 6 months, with the odds
      ratio being 0.35 (95% CI 0.19 - 0.64). Having only a moderate dislike or a liking
      of alcohol advertisements was positively associated with alcohol use in the past
      6 months among the study participants (OR 2.90 and 2.84, respectively). Age,
      gender, educational status and socioeconomic status were not independently
      associated with alcohol consumption. CONCLUSIONS: Exposure to alcohol marketing
      and not being strongly averse to advertisements of alcohol brands and products
      were associated with alcohol use among adolescents. The results have implications
      for policies on alcohol marketing in SA.

PMID- 30182906
TI  - Mike Kew: A physician-scientist, teacher and role model extraordinaire with an
      enduring influence on excellence and mentorship in medicine.

PMID- 30182907
TI  - Towards the elimination of hepatitis B and hepatocellular carcinoma.
AB  - Hepatitis B (HBV) remains a global health problem despite the availability of
      effective vaccines since 1982 and effective antiviral therapy. The global burden
      of disease is substantial, with HBV resulting in 887 220 deaths in 2015: acute
      hepatitis (87 076), cirrhosis (462 690) and hepatocellular carcinoma (337 454).
      The World Health Organization has a vision to eliminate viral hepatitis as a
      public health threat by 2030. Although HBV and its associated complications of
      cirrhosis, liver failure and hepatocellular carcinoma are entirely vaccine
      preventable, there is no cure for chronic hepatitis B as yet. HBV elimination
      strategies will need to focus on effective and implementable preventive and
      therapeutic strategies such as upscaling HBV birth-dose vaccination, full HBV
      vaccine coverage, vaccination of high-risk groups, prevention of mother-to-child
      transmission, and identification of HBV-infected individuals and linkage to care
      with sustainable access to antiviral therapy.

PMID- 30182908
TI  - Molecular characteristics and clinical relevance of African genotypes and
      subgenotypes of hepatitis B virus.
AB  - Hepatitis B virus (HBV), a DNA virus, replicates via an RNA intermediate,
      through reverse transcription catalysed by the viral polymerase that lacks proof
      reading ability. Thus sequence heterogeneity is a feature of HBV being classified
      into at least 9 genotypes and over 35 subgenotypes. Africa has a high diversity
      of genotypes/subgenotypes, with distinct geographical distributions. Genotype A
      is found mainly in south-eastern Africa, E in western and central Africa and D
      prevailing in northern Africa. Outside Africa, subgenotype A2 prevails and A1 in
      Africa, which was the most probable source of its dispersal to Asia and Latin
      America, as a result of slave and trade routes. Genotype E is also an African
      strain with low genetic diversity, intimating a recent emergence of 200 years or
      less, with its dispersal outside Africa occurring as a result of modern human
      migrations. Carriers of subgenotype A1 and genotype E display unique clinical
      features. A1-infected individuals have low viral loads, low frequency of HBeAg
      positivity, horizontal transmission of HBV, higher levels of liver damage and a
      higher risk of developing hepatocellular carcinoma. In contrast, individuals
      infected with genotype E have high viral loads, high frequency of HBeAg
      positivity and transmit HBV perinatally. Although 15% of HBV infections in HIV
      infected Africans are HBsAg-negative, the true occult phenotype of low viral
      loads is found in only 7% and 65% of individuals infected with subgenotype A1 and
      genotypes E (or D), respectively. Molecular and functional characteristics of
      these African HBV strains can account for their different clinical
      manifestations.

PMID- 30182909
TI  - Current and future directions for the management of hepatitis B.
AB  - Hepatitis B virus vaccination, while effective in reducing incident chronic
      hepatitis B in endemic regions, will not have the desired impact on the rates of
      end-stage liver disease in chronically infected persons. A large reservoir of
      chronic infection remains and needs to be managed effectively. Over three
      decades, interferon alpha (IFNalpha), and nucleoside analogue therapies have
      reduced the morbidity and mortality associated with chronic hepatitis B by
      suppressing viral replication and retarding the progression to cirrhosis and the
      development of hepatocellular carcinoma (HCC). The preferential preservation of
      covalently closed circular (cccDNA) and capsid reverse transcriptase-cccDNA
      interactions during nucleoside analogue therapy currently prevent cure; the
      majority of patients require continuous maintenance suppressive therapy. In
      selected patients nucleoside analogues may be stopped. New targets for drug
      therapy need to be directed at inhibiting intracellular HBV replication,
      transcription and translation pathways to enhance the likelihood of a cure in the
      host. Such cures for chronic hepatitis B infection will require several
      synergistic therapies to achieve either complete eradication of replicative
      intermediates from the host (cure), or more probably, a functional cure defined
      as loss of hepatitis B surface antigen. Hampering such development is the lack of
      a proven serological surrogate for cccDNA to evaluate treatment efficacy. This
      review outlines the pathophysiology of the virus, the host immunological
      responses and current therapies. Understanding the interactions between HBV and
      the host remains fundamental to guide correct sequencing and combinations of
      treatment with either host or viral-targeting agents to achieve higher rates of
      cure.

PMID- 30182910
TI  - The global elimination of hepatitis C?
AB  - Globally, 71 million people are thought to be viraemic for hepatitis C. The
      advent of short course all oral direct acting antiviral curative therapy for the
      virus has put the ideal of the global elimination of this virus within reach.
      Multiple efforts will be required to achieve this through identifying patients
      currently infected and preventing further transmission through rapid linkage to
      treatment while a vaccine remains tenaciously elusive.

PMID- 30182911
TI  - Hepatocellular carcinoma: Epidemiology, pathogenesis and surveillance -
      implications for sub-Saharan Africa.
AB  - Hepatocellular carcinoma (HCC) originates from hepatocytes usually secondary to
      chronic inflammation and cirrhosis. It is an important disease of global
      significance with a high incidence and mortality. It is the fifth and eighth most
      common cancer in males and females, respectively. HCC is also extremely lethal;
      in 2015 it was the second and sixth most common cause of death from cancer in
      males and females, respectively. Chronic viral hepatitis B and C are the most
      frequent risk factors for the development of HCC, and the global distribution of
      HCC largely mirrors that of chronic viral hepatitis. More recently, there has
      been a notable increase in the incidence of HCC as a result of obesity-related
      fatty liver disease. Here, we review the epidemiology of HCC, examine recent
      advances in our understanding of the pathogenesis of HCC, discuss the
      implications for identification of potential therapeutic targets, and provide the
      most updated recommendations on surveillance for HCC, with particular attention
      to the unique challenges and potential opportunities to reduce the burden of
      illness and death from HCC in sub-Saharan Africa.

PMID- 30182912
TI  - Molecular and cellular oncogenic mechanisms in hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC), as the fifth most diagnosed cancer in the world
      and the third leading cause of death, is a global health concern. Research
      stimulated by the dismal prognosis of HCC has led to significant advances in the
      understanding of its aetio-pathogenesis. Dysregulation of genetic, epigenetic and
      signalling pathways as well as tumour immunological escape mechanisms are
      implicated in the development of HCC. This review summarises the current
      knowledge of these mechanisms and argues that it is only through further
      understanding of their role in hepatocarcinogenesis, that new effective therapies
      can be developed.

PMID- 30182913
TI  - Prevention of hepatocellular carcinoma with antiviral therapy.
AB  - Chronic viral hepatitis types B and C may eventually lead to the development of
      hepatocellular carcinoma. Although hepatitis B is readily preventable by
      vaccination, there is growing evidence that antiviral therapy directed against
      hepatitis B may reduce the risk of liver cancer among those already infected.
      There is no vaccine against hepatitis C, but the evidence is now strong that
      antiviral therapy with sustained virological response (viral cure) reduces, but
      does not eliminate, the risk of hepatocellular carcinoma.

PMID- 30182914
TI  - Hepatocellular carcinoma in sub-Saharan Africa - the way forward.
AB  - Michael Kew's academic career spans five decades, representing the most
      proliferative and pioneering years of the expanded knowledge on all aspects of
      hepatocellular cancer (HCC). The preceding articles in this Festschrift bear
      testimony to his legacy, engagement, enthusiasm, dedication and ability to
      inspire others. His enormous contribution, mostly originating from research in
      sub-Saharan Africa (SSA), contributed immensely to the knowledge and evidence on
      which current understanding of the disease is based.

PMID- 30182915
TI  - Migration Medicine: Notes on a Young Science?.

PMID- 30182916
TI  - Epidemiology and Transmission of Respiratory Infections in Thai Army Recruits: A
      Prospective Cohort Study.
AB  - Military recruits are at high risk of respiratory infections. However, limited
      data exist on military populations in tropical settings, where the epidemiology
      of respiratory infections differs substantially from temperate settings. We
      enrolled recruits undertaking a 10-week military training at two Royal Thai Army
      barracks between May 2014 and July 2015. We used a multiplex respiratory panel to
      analyze nose and throat swabs collected at the start and end of the training
      period, and from participants experiencing respiratory symptoms during follow-up.
      Paired sera were tested for influenza seroconversion using a hemagglutinin
      inhibition assay. Overall rates of upper respiratory illness and influenza-like
      illness were 3.1 and 2.0 episodes per 100 person-weeks, respectively. A pathogen
      was detected in 96% of samples. The most commonly detected microbes were
      Haemophilus influenzae type B (62.7%) or non-type B (58.2%) and rhinovirus
      (22.4%). At baseline, bacterial colonization was high and included H. influenzae
      type B (82.3%), H. influenzae non-type B (31.5%), Klebsiella pneumoniae (14.6%),
      Staphylococcus aureus (8.5%), and Streptococcus pneumoniae (8.5%). At the end of
      follow-up, colonization with H. influenzae non-type B had increased to 74.1%, and
      S. pneumoniae to 33.6%. In the serology subset, the rate of influenza infection
      was 3.4 per 100 person-months; 58% of influenza infections resulted in clinical
      disease. Our study provides key data on the epidemiology and transmission of
      respiratory pathogens in tropical settings. Our results emphasize the need for
      improved infection prevention and control in military environments, given the
      high burden of illness and potential for intense transmission of respiratory
      pathogens.

PMID- 30182917
TI  - Factors Associated with the 18-Month Cumulative Incidence of Seroconversion of
      Active Infection with Taenia solium Cysticercosis: A Cohort Study among Residents
      of 60 Villages in Burkina Faso.
AB  - Taeniasis/cysticercosis (CC) is an important disease complex with significant
      burden. This large-scale cohort study aimed at estimating and exploring
      individual- and village-level factors associated with the cumulative incidences
      of seroconversion (SC) and seroreversion (SR) of active human CC in three
      provinces of Burkina Faso. In 60 villages, blood samples were collected and
      interviews regarding sociodemographic variables and knowledge, attitude, and
      practices toward the disease complex were conducted at baseline and 18-month
      follow-up (N = 2,211), with the presence of active CC being determined using the
      B158/B60 antigen enzyme-linked immunosorbent assay (Ag-ELISA). The 18-month Ag SC
      and SR were estimated at 3.3% (95% confidence interval [CI]: 2.6; 4.2%) and 35.8%
      (95% CI: 24.5; 48.5%), respectively. Marked provincial differences were found for
      the 18-month Ag SC (Boulkiemde: cumulative incidence ratio [CIR]: 2.41 (95% CI:
      1.21; 4.78) and Nayala: CIR: 3.28 (95% CI: 1.37; 7.84), compared with Sanguie),
      while not being significantly associated with other sociodemographic factors. A
      continued refraining from pork consumption was associated with a lower 18-month
      Ag SC (CIR: 0.55 [95% CI: 0.28; 1.07]), whereas at the village level, the
      percentage of households owning pigs was associated with a higher 18-month Ag SC
      (CIR: 1.03 [95% CI: 1.01; 1.05]). In conclusion, this is one of few cohort
      studies and the first to have enough power to assess possible causal links
      between individual- and village-level variables and CC in humans. Variables
      linked to province, pig raising, and pork consumption behaviors were found to
      cause Ag SC in humans. The latter results further support the importance of
      adopting a One Health approach to the control of CC.

PMID- 30182918
TI  - Mosquito and Virus Surveillance as a Predictor of Human Ross River Virus
      Infection in South-West Western Australia: How Useful Is It?
AB  - Mosquito and virus surveillance systems are widely used in Western Australia (WA)
      to support public health efforts to reduce mosquito-borne disease. However, these
      programs are costly to maintain on a long-term basis. Therefore, we aimed to
      assess the validity of mosquito numbers and Ross River virus (RRV) isolates from
      surveillance trap sites as predictors of human RRV cases in south-west WA between
      2003 and 2014. Using negative binomial regression modeling, mosquito surveillance
      was found to be a useful tool for predicting human RRV cases. In eight of the
      nine traps, when adjusted for season, there was an increased risk of RRV cases
      associated with elevated mosquito numbers detected 1 month before the onset of
      human cases for at least one quartile compared with the reference group. The most
      predictive urban trap sites were located near saltmarsh mosquito habitat,
      bushland that could sustain macropods and densely populated residential suburbs.
      This convergence of environments could allow enzootic transmission of RRV to
      spillover and infect the human population. Close proximity of urban trap sites to
      each other suggested these sites could be reduced. Ross River virus isolates were
      infrequent at some trap sites, so ceasing RRV isolation from mosquitoes at these
      sites or where isolates were not predictive of human cases could be considered.
      In future, trap sites could be reduced for routine surveillance, allowing other
      environments to be monitored to broaden the understanding of RRV ecology in the
      region. A more cost-effective and efficient surveillance program may result from
      these modifications.

PMID- 30182919
TI  - St. Louis Encephalitis Virus Disease in the United States, 2003-2017.
AB  - St. Louis encephalitis virus (SLEV), an arthropod-borne flavivirus, can cause
      disease presentations ranging from mild febrile illness through severe
      encephalitis. We reviewed U.S. national SLEV surveillance data for 2003 through
      2017, including human disease cases and nonhuman infections. Over the 15-year
      period, 198 counties from 33 states and the District of Columbia reported SLEV
      activity; 94 (47%) of those counties reported SLEV activity only in nonhuman
      species. A total of 193 human cases of SLEV disease were reported, including 148
      cases of neuroinvasive disease. A median of 10 cases were reported per year. The
      national average annual incidence of reported neuroinvasive disease cases was
      0.03 per million. States with the highest average annual incidence of reported
      neuroinvasive disease cases were Arkansas, Arizona, and Mississippi. No large
      outbreaks occurred during the reporting period. The most commonly reported
      clinical syndromes were encephalitis (N = 116, 60%), febrile illness (N = 35,
      18%), and meningitis (N = 25, 13%). Median age of cases was 57 years (range 2-89
      years). The case fatality rate was 6% (11/193) and all deaths were among patients
      aged > 45 years with neuroinvasive disease. Nonhuman surveillance data indicated
      wider SLEV activity in California, Nevada, and Florida than the human data alone
      suggested. Prevention depends on community efforts to reduce mosquito populations
      and personal protective measures to decrease exposure to mosquitoes.

PMID- 30182920
TI  - Altered Systemic Adipokine Levels in Pulmonary Tuberculosis and Changes following
      Treatment.
AB  - Pulmonary tuberculosis (PTB) is associated with modulation of levels of
      adipokines, specifically adiponectin and leptin, but the effect of standard
      antituberculosis treatment (ATT) on the systemic levels of adiponectin, resistin,
      and leptin has not been well explored. To identify the association of adipokines
      with PTB and their relationship with disease severity and bacterial burden, we
      measured the levels of adiponectin, resistin, and leptin in PTB individuals and
      compared them with latent tuberculosis (LTB) and healthy control (HC)
      individuals. Pulmonary tuberculosis was characterized by diminished circulating
      levels of adiponectin and leptin and heightened circulating levels of resistin in
      comparison to that in LTB and HC individuals. However, PTB with bilateral or
      cavitary disease did not exhibit any increased systemic levels of these
      adipokines in comparison with those with unilateral or non-cavitary disease,
      respectively. In addition, none of the adipokines exhibited a positive
      correlation with bacterial burdens, but adiponectin alone exhibited a negative
      correlation with body mass index in PTB individuals. Finally, on successful
      completion of ATT, PTB individuals exhibited significantly increased levels of
      adiponectin and leptin and significantly decreased levels of resistin. Therefore,
      our data identify an important association of systemic adipokine levels with PTB
      disease and its alteration following ATT.

PMID- 30182921
TI  - Case Report: Plasmodium knowlesi Infection with Rhabdomyolysis in a Japanese
      Traveler to Palawan, the Philippines.
AB  - Skeletal muscle is known to be damaged by falciparum malaria via sequestration of
      infected erythrocytes. We present a case of rhabdomyolysis caused by Plasmodium
      knowlesi infection. The patient had fever, myalgia, and muscle weakness 5 days
      after returning to Japan from Palawan, the Philippines. Blood test revealed
      thrombocytopenia and an elevated creatine kinase level. Although rhabdomyolysis
      resolved with fluid therapy, fever of 24-hour cycle continued and
      thrombocytopenia intensified. On day 7 of illness, Giemsa-stained thin blood
      smear revealed malaria parasites, with a parasite count of 2,380/MUL, which were
      morphologically indistinguishable between P. knowlesi and Plasmodium malariae.
      Rapid diagnostic test showed a negative result. The pathogen was later confirmed
      to be P. knowlesi by nested polymerase chain reaction (PCR). The patient was
      successfully treated with artemether/lumefantrine. This case suggests that
      knowlesi malaria might be able to cause skeletal muscle damage.

PMID- 30182922
TI  - Epidemiology of Hepatitis A and Hepatitis E Based on Laboratory Surveillance Data
      India, 2014-2017.
AB  - Hepatitis A and hepatitis E viruses (HAV and HEV) are the most common etiologies
      of viral hepatitis in India. To better understand the epidemiology of these
      infections, laboratory surveillance data generated during 2014-2017, by a network
      of 51 virology laboratories, were analyzed. Among 24,000 patients tested for both
      HAV and HEV, 3,017 (12.6%) tested positive for HAV, 3,865 (16.1%) for HEV, and
      320 (1.3%) for both HAV and HEV. Most (74.6%) HAV patients were aged <= 19 years,
      whereas 76.9% of HEV patients were aged >= 20 years. These laboratories diagnosed
      12 HAV and 31 HEV clusters, highlighting the need for provision of safe drinking
      water and improvements in sanitation. Further expansion of the laboratory network
      and continued surveillance will provide data necessary for informed decision
      making regarding introduction of hepatitis-A vaccine into the immunization
      program.

PMID- 30182923
TI  - Risk Factors for Malaria Infection in Central Madagascar: Insights from a Cross
      Sectional Population Survey.
AB  - Community prevalence of infection is a widely used, standardized metric for
      evaluating malaria endemicity. Conventional methods for measuring prevalence
      include light microscopy and rapid diagnostic tests (RDTs), but their detection
      thresholds are inadequate for diagnosing low-density infections. The significance
      of submicroscopic malaria infections is poorly understood in Madagascar, a
      country of heterogeneous malaria epidemiology. A cross-sectional community survey
      in the western foothills of Madagascar during the March 2014 transmission season
      found malaria infection to be predominantly submicroscopic and asymptomatic.
      Prevalence of Plasmodium infection diagnosed by microscopy, RDT, and molecular
      diagnosis was 2.4%, 4.1%, and 13.8%, respectively. This diagnostic discordance
      was greatest for Plasmodium vivax infection, which was 98.5% submicroscopic.
      Village location, insecticide-treated bednet ownership, and fever were
      significantly associated with infection outcomes, as was presence of another
      infected individual in the household. Duffy-negative individuals were diagnosed
      with P. vivax, but with reduced odds relative to Duffy-positive hosts. The
      observation of high proportions of submicroscopic infections calls for a wider
      assessment of the parasite reservoir in other regions of the island, particularly
      given the country's current focus on malaria elimination and the poorly
      documented distribution of the non-P. falciparum parasite species.

PMID- 30182925
TI  - Basophilic Stippling and Chronic Lead Poisoning

PMID- 30182924
TI  - Plasma Ischemia-Modified Albumin Levels and Dynamic Thiol/Disulfide Balance in
      Sickle Cell Disease: A Case-Control Study
AB  - Objective: Sickle cell disease (SCD), described as a group of inherited blood
      disorders, affects millions of people throughout the world and is particularly
      common in the southern part of Turkey. We aimed to determine the relationship
      between ischemia-modified albumin (IMA) and the dynamic thiol/disulfide balance
      in SCD. Materials and Methods: Fifty-four adult SCD patients and 30 healthy
      controls were included in the study. The 54 adult patients included 30 (56%)
      males and 24 (44%) females with a mean age of 28.3+/-8.4 years (minimum-maximum:
      18-46 years). Of the 54 patients, 46 had homozygous sickle cell anemia (HbSS) and
      8 had sickle/beta-thalassemia (HbS/beta+-thalassemia). Fasting blood samples were
      collected. After centrifugation at 1500*g for 10 min, plasma samples were
      portioned and stored at -80  degrees C. IMA levels were determined by albumin
      cobalt binding test, a colorimetric method. Total and native thiols and disulfide
      were analyzed with a novel spectrophotometric method. Results: We found
      significantly lower levels of native thiol (-SH) (284.0+/-86.3 umol/L), disulfide
      levels (14.6+/-7 umol/L), and total thiols (-SH + -S-S-) (313.0+/-89.3 umol/L) in
      SCD patients compared to healthy controls (respectively 417.0+/-54.2, 22.7+/
      11.3, and 462.0+/-58.7 umol/L). Plasma albumin levels (34.9+/-7.9 g/L) were lower
      and IMA levels (13.6+/-3.1 g/L) were higher in SCD patients compared to controls
      (respectively 43.5+/-3.1 and 8.4+/-1.6 g/L). Plasma albumin levels were strongly
      correlated with both plasma native (r=0.853; p=0.0001) and total thiols (r=0.866;
      p=0.0001). Conclusion: Decreased plasma native and total thiol levels and
      increased IMA levels are related to increased oxidative stress and provide an
      indirect and quick reflection of the oxidative damage in SCD patients.

PMID- 30182926
TI  - Spin waves in disordered materials.
AB  - We present an efficient methodology to study spin waves in disordered materials.
      The approach is based on a Heisenberg model and enables calculations of magnon
      properties in spin systems with disorder of an arbitrary kind and concentration
      of impurities. Disorder effects are taken into account within two complementary
      approaches. Magnons in systems with substitutional (uncorrelated) disorder can be
      efficiently calculated within a single-site coherent potential approximation for
      the Heisenberg model. From the computation point of view the method is
      inexpensive and directly applicable to systems like alloys and doped materials.
      It is shown that it performs exceedingly well across all concentrations and wave
      vectors. Another way is the direct numerical simulation of large supercells using
      a configurational average over possible samples. This approach is applicable to
      systems with an arbitrary kind of disorder. The effective interaction between
      magnetic moments entering the Heisenberg model can be obtained from first
      principles using a self-consistent Green function method within the density
      functional theory. Thus, our method can be viewed as an ab initio approach and
      can be used for calculations of magnons in real materials.

PMID- 30182927
TI  - NIR induced modulation of the red emission from erbium ions for selective
      lanthanide imaging.
AB  - Upon direct excitation with green light (522 nm), Er3+ ion doped nanoparticles
      feature a number of radiative and non-radiative decay pathways, leading to
      distinct and sharp emission lines in the visible and near-infrared (NIR) range.
      Here we apply, in addition to continuous 522 nm irradiation, a modulated NIR
      irradiation (1143 nm) to actively control and modulate the red emission intensity
      (around 650 nm). The modulation of red Er3+ ion emission at a chosen frequency
      allows us to reconstruct fluorescence images from the Fourier transform amplitude
      at this particular frequency. Since only the emission from the Er3+ ion is
      modulated, it allows to selectively recover the lanthanide specific signal,
      removing any non-modulated auto-fluorescence or background emission resulting
      from the continuous 522 nm excitation. The modulated emission of specific
      lanthanides can open up new detection opportunities for selective signal
      recovery.

PMID- 30182928
TI  - Bottom-up biofabrication using microfluidic techniques.
AB  - Nature builds living organisms in a bottom-up fashion, starting from the
      expression of genetic information on a cellular level, to the proliferation,
      differentiation, and self-assembly of cells into tissues/organs during embryo
      development and wound-healing processes. To mimic this bottom-up approach, it is
      essential to handle and manipulate small-scale biomaterials using specific
      technologies, such as microfluidic techniques. Microfluidics provides the tool
      sets that deal with the behavior, precise control and manipulation of small
      amounts of fluids. Since the handling performed in aqueous environment guarantees
      the well-preserved bioactivities of biomaterials, microfluidic techniques show
      unique and critical advantages for biofabrication purposes. In this review, we
      report the recent progress on the bottom-up biofabrication using microfluidic
      techniques, such as the fabrication of microtissues, bioprinting of cell-laden
      tissue scaffolds, and organ-on-a-chip. As future perspectives, the deeper
      convergence of bottom-up approaches with top-down approaches as well as
      microfluidic-enabled vascularization of thick tissues is anticipated to have
      enormous impacts on the field of biofabrication.

PMID- 30182929
TI  - Rigid units revisited.

PMID- 30182930
TI  - An algebraic approach to cooperative rotations in networks of interconnected
      rigid units.
AB  - Crystalline solids consisting of three-dimensional networks of interconnected
      rigid units are ubiquitous amongst functional materials. In many cases,
      application-critical properties are sensitive to rigid-unit rotations at low
      temperature, high pressure or specific stoichiometry. The shared atoms that
      connect rigid units impose severe constraints on any rotational degrees of
      freedom, which must then be cooperative throughout the entire network. Successful
      efforts to identify cooperative-rotational rigid-unit modes (RUMs) in crystals
      have employed split-atom harmonic potentials, exhaustive testing of the
      rotational symmetry modes allowed by group representation theory, and even simple
      geometric considerations. This article presents a purely algebraic approach to
      RUM identification wherein the conditions of connectedness are used to construct
      a linear system of equations in the rotational symmetry-mode amplitudes.

PMID- 30182932
TI  - Comments on A new theory for X-ray diffraction.
AB  - In an article entitled A new theory for X-ray diffraction [Fewster (2014). Acta
      Cryst. A70, 257-282], hereafter referred to as NTXRD, it is claimed that when X
      rays are scattered from a small crystallite, whatever its size and shape, the
      diffraction pattern will contain enhanced scattering at angles of exactly
      2thetaB, whatever the orientation of the crystal. It is claimed that in this way
      scattering from a powder, with randomly oriented crystals, gives rise to Bragg
      scattering even if the Bragg condition is never satisfied by an individual
      crystallite. The claims of the theory put forward in NTXRD are examined and they
      are found to be in error. Whilst for a certain restricted set of shapes of
      crystals it is possible to obtain some diffraction close to (but not exactly at)
      the Bragg angle as the crystallite is oriented away from the Bragg condition,
      this is generally not the case. Furthermore, contrary to the claims made within
      NTXRD, the recognition of the origin of the type of effects described is not new,
      and has been known since the earliest days of X-ray diffraction.

PMID- 30182931
TI  - Measuring stress-induced martensite microstructures using far-field high-energy
      diffraction microscopy.
AB  - Modern X-ray diffraction techniques are now allowing researchers to collect long
      desired experimental verification data sets that are in situ, three-dimensional,
      on the same length scales as critical microstructures, and using bulk samples.
      These techniques need to be adapted for advanced material systems that undergo
      combinations of phase transformation, twinning and plasticity. One particular
      challenge addressed in this article is direct analysis of martensite phases in
      far-field high-energy diffraction microscopy experiments. Specifically, an
      algorithmic forward model approach is presented to analyze phase transformation
      and twinning data sets of shape memory alloys. In the present implementation of
      the algorithm, the crystallographic theory of martensite (CTM) is used to predict
      possible martensite microstructures (i.e. martensite orientations, twin mode,
      habit plane, twin plane and twin phase fractions) that could form from the parent
      austenite structure. This approach is successfully demonstrated on three single-
      and near-single-crystal NiTi samples where the fundamental assumptions of the CTM
      are not upheld. That is, the samples have elastically strained lattices,
      inclusions, precipitates, subgrains, R-phase transformation and/or are not an
      infinite plate. The results indicate that the CTM still provides structural
      solutions that match the experiments. However, the widely accepted maximum work
      criterion for predicting which solution of the CTM should be preferred by the
      material does not work in these cases. Hence, a more accurate model that can
      simulate these additional structural complexities can be used within the
      algorithm in the future to improve its performance for non-ideal materials.

PMID- 30182933
TI  - Response to Fraser & Wark's comments on A new theory for X-ray diffraction.
AB  - The criticisms of my theory, as given by Fraser & Wark [(2018), Acta Cryst. A74,
      447-456], are built on a misunderstanding of the concept and the methodology I
      have used. The assumption they have made rules out my description from which they
      conclude that my theory is proved to be wrong. They assume that I have
      misunderstood the diffraction associated with the shape of a crystal and my
      calculation is only relevant to a parallelepiped and even that I have got wrong.
      It only appears wrong to Fraser & Wark because the effect I predict has nothing
      to do with the crystal shape. The effect though can be measured as well as the
      crystal shape effects. This response describes my reasoning behind the theory,
      how it can be related to the Ewald sphere construction, and the build-up of the
      full diffraction pattern from all the scatterers in a stack of planes. It is the
      latter point that makes the Fraser & Wark analysis incomplete. The description
      given in this article describes my approach much more precisely with reference to
      the Ewald sphere construction. Several experiments are described that directly
      measure the predictions of the new theory, which are explained with reference to
      the Ewald sphere description. In its simplest terms the new theory can be
      considered as giving a thickness to the Ewald sphere surface, whereas in the
      conventional theory it has no thickness. Any thickness immediately informs us
      that the scattering from a peak at the Bragg angle does not have to be in the
      Bragg condition to be observed. I believe the conventional theory is a very good
      approximation, but as soon as it is tested with careful experiments it is shown
      to be incomplete. The new theory puts forward the idea that there is persistent
      intensity at the Bragg scattering angle outside the Bragg condition. This
      intensity is weak (~10-5) but can be observed in careful laboratory experiments,
      despite being on the limit of observation, yet it has a profound impact on how we
      should interpret diffraction patterns.

PMID- 30182934
TI  - Structure evolution of h.c.p./c.c.p. metal oxide interfaces in solid-state
      reactions.
AB  - The structure of crystalline interfaces plays an important role in solid-state
      reactions. The Al2O3/MgAl2O4/MgO system provides an ideal model system for
      investigating the mechanisms underlying the migration of interfaces during
      interface reaction. MgAl2O4 layers have been grown between Al2O3 and MgO, and the
      atomic structure of Al2O3/MgAl2O4 interfaces at different growth stages was
      characterized using aberration-corrected scanning transmission electron
      microscopy. The oxygen sublattice transforms from hexagonal close-packed (h.c.p.)
      stacking in Al2O3 to cubic close-packed (c.c.p.) stacking in MgAl2O4. Partial
      dislocations associated with steps are observed at the interface. At the reaction
      controlled early growth stages, such partial dislocations coexist with the edge
      dislocations. However, at the diffusion-controlled late growth stages, such
      partial dislocations are dominant. The observed structures indicate that
      progression of the Al2O3/MgAl2O4 interface into Al2O3 is accomplished by the
      glide of partial dislocations accompanied by the exchange of Al3+ and Mg2+
      cations. The interface migration may be envisaged as a plane-by-plane zipper-like
      motion, which repeats along the interface facilitating its propagation. MgAl2O4
      grains can adopt two crystallographic orientations with a twinning orientation
      relationship, and grow by dislocations gliding in opposite directions. Where the
      oppositely propagating partial dislocations and interface steps meet, interlinked
      twin boundaries and incoherent Sigma3 grain boundaries form. The newly grown
      MgAl2O4 grains compete with each other, leading to a growth selection and
      successive coarsening of the MgAl2O4 grains. This understanding could help to
      interpret the interface reaction or phase transformation of a wide range of
      materials that exhibit a similar h.c.p./c.c.p. transition.

PMID- 30182935
TI  - Estimating the structure factors in X-ray diffraction.
AB  - This article takes the concepts of the 'new diffraction theory' [Fewster (2014).
      Acta Cryst. A70, 257-282] and examines the implications for the interpretation of
      experimental results and the estimation of structure factors. Further
      experimental evidence is included to justify the conclusions in the theory,
      showing that the residual intensity at twice the Bragg angle is a diffraction
      effect and not associated with the crystal shape. This 'enhancement' effect is
      independent of whether kinematical or dynamical theories are applied and can lead
      to a clearer understanding of how the dynamical effects are suppressed in
      imperfect crystals. By applying the idea that the higher-order peaks are due to
      path lengths of nlambda, it is shown that 'systematically absent' reflections in
      the conventional theory may not be absent. Because this new theory considers the
      intensity to be more distributed, it suggests that the entire structure factor
      can be difficult to capture by experiment. This article suggests some routes to
      achieve a good approximation of the structure factors for typical methods of data
      collection. Any measurement of intensity with background removal will exclude
      some of the distributed intensity, again leading to an underestimate of the
      structure factors, and therefore the missing intensity needs to be estimated.

PMID- 30182936
TI  - Explicit construction of the Voronoi and Delaunay cells of W(An) and W(Dn)
      lattices and their facets.
AB  - Voronoi and Delaunay (Delone) cells of the root and weight lattices of the
      Coxeter-Weyl groups W(An) and W(Dn) are constructed. The face-centred cubic
      (f.c.c.) and body-centred cubic (b.c.c.) lattices are obtained in this context.
      Basic definitions are introduced such as parallelotope, fundamental simplex,
      contact polytope, root polytope, Voronoi cell, Delone cell, n-simplex, n
      octahedron (cross polytope), n-cube and n-hemicube and their volumes are
      calculated. The Voronoi cell of the root lattice is constructed as the dual of
      the root polytope which turns out to be the union of Delone cells. It is shown
      that the Delone cells centred at the origin of the root lattice An are the
      polytopes of the fundamental weights omega1, omega2,..., omegan and the Delone
      cells of the root lattice Dn are the polytopes obtained from the weights omega1,
      omegan-1 and omegan. A simple mechanism explains the tessellation of the root
      lattice by Delone cells. It is proved that the (n-1)-facet of the Voronoi cell of
      the root lattice An is an (n-1)-dimensional rhombohedron and similarly the (n-1)
      facet of the Voronoi cell of the root lattice Dn is a dipyramid with a base of an
      (n-2)-cube. The volume of the Voronoi cell is calculated via its (n-1)-facet
      which in turn can be obtained from the fundamental simplex. Tessellations of the
      root lattice with the Voronoi and Delone cells are explained by giving examples
      from lower dimensions. Similar considerations are also worked out for the weight
      lattices An* and Dn*. It is pointed out that the projection of the higher
      dimensional root and weight lattices on the Coxeter plane leads to the h-fold
      aperiodic tiling, where h is the Coxeter number of the Coxeter-Weyl group. Tiles
      of the Coxeter plane can be obtained by projection of the two-dimensional faces
      of the Voronoi or Delone cells. Examples are given such as the Penrose-like
      fivefold symmetric tessellation by the A4 root lattice and the eightfold
      symmetric tessellation by the D5 root lattice.

PMID- 30182937
TI  - Incorporating particle symmetry into orientation determination in single-particle
      imaging.
AB  - In coherent-diffraction-imaging experiments X-ray diffraction patterns of
      identical particles are recorded. The particles are injected into the X-ray free
      electron laser (XFEL) beam in random orientations. If the particle has symmetry,
      finding the orientation of a pattern can be ambiguous. With some modifications,
      the correlation-maximization method can find the relative orientations of the
      diffraction patterns for the case of symmetric particles as well. After
      convergence, the correlation maps show the symmetry of the particle and can be
      used to determine the symmetry elements and their orientations. The C factor,
      slightly modified for the symmetric case, can indicate the consistency of the
      assembled three-dimensional intensity distribution.

PMID- 30182938
TI  - Variation of second-order piezoelectric coefficients with respect to a finite
      strain measure.
AB  - In this article the consequence of a change of finite strain measure is
      theoretically considered for nonlinear piezoelectric crystals. Analytical
      predictions show that second-order piezoelectric coefficients are finite strain
      measure dependent. Therefore, the use of any finite strain measure in
      constitutive modelling of piezoelectric materials requires an adequate choice of
      higher-order piezoelectric coefficients. This allows one to avoid unwanted
      corrections to the elastic and electric fields in the case of nonlinear modelling
      of piezoelectric materials, e.g. for piezoelectric heterostructures such as
      quantum wells or dots. A general transformation formula for second-order
      piezoelectric coefficients (elastostriction) is derived. As an example, specific
      transformation formulae for two common crystallographic classes, namely {?bar
      4}3m and 6mm, are presented. The piezoelectric coefficients for GaN and GaAs
      crystals, as representative cases of these crystal classes, are recalculated and
      their dependence on the strain measure is demonstrated. A further implication of
      that effect is that a complete set of second-order piezoelectric coefficients
      should contain additional information about the strain measure applied during
      calculations or measurements.

PMID- 30182939
TI  - Fast analytical evaluation of intermolecular electrostatic interaction energies
      using the pseudoatom representation of the electron density. I. The Lowdin alpha
      function method.
AB  - The previously reported [Volkov et al. (2004). Chem. Phys. Lett. 391, 170-175]
      exact potential and multipole moment (EP/MM) method for evaluation of
      intermolecular electrostatic interaction energies using the nuclei-centered
      pseudoatom representation of electron densities is significantly improved in
      terms of both speed and accuracy by replacing the numerical quadrature
      integration of the exact potential with a fully analytical technique. The
      resulting approach, incorporated in the XDPROP module of the software package XD,
      has been tested on several molecular systems ranging in size from water-water to
      dodecapeptide-dodecapeptide dimers using electron densities constructed via the
      University at Buffalo Aspherical Atom Databank. The improved hybrid method
      provides electrostatic interaction energies within the uncertainty of <=0.2 kJ
      mol-1 for all benchmark systems. The running time for a dimer of a sizable, 225
      atom dodecapeptide is under 4 s on a 2012 central processing unit (2.8 GHz AMD
      Opteron 6348) and under 3 s on a relatively modern processor (2.8 GHz Intel Xeon
      E3-1505M v5).

PMID- 30182940
TI  - The phase problem for two-dimensional crystals. II. Simulations.
AB  - Phasing of diffraction data from two-dimensional crystals using only minimal
      molecular envelope information is investigated by simulation. Two-dimensional
      crystals are an attractive target for studying membrane proteins using X-ray free
      electron lasers, particularly for dynamic studies at room temperature.
      Simulations using an iterative projection algorithm show that phasing is feasible
      with fairly minimal molecular envelope information, supporting recent uniqueness
      results for this problem [Arnal & Millane (2017). Acta Cryst. A73, 438-448]. The
      effects of noise and likely requirements for structure determination using X-ray
      free-electron laser sources are investigated.

PMID- 30182941
TI  - Specular reflection intensity modulated by grazing-incidence diffraction in a
      wide angular range.
AB  - Grazing-incidence X-ray diffraction (GID) is a well known technique for the
      characterization of crystal surfaces. A theoretical study has been performed of
      the sensitivity of GID to the structure of a crystal surface and distorted
      nanometre-thin surface layers. To simulate GID from crystals that have a complex
      subsurface structure, a matrix formalism of the dynamical diffraction theory has
      been applied. It has been found that the azimuthal rocking curves of a crystal
      that has a distorted subsurface, measured over a wide angular range, show
      asymmetric thickness oscillations with two distinguishable sets of frequencies:
      one corresponding to the diffraction in the single-crystal subsurface layer and
      the second corresponding to the diffraction in the single-crystal substrate.
      Therefore, azimuthal rocking curves allow characterization of the subsurface
      structure of a single crystal. Furthermore, thickness oscillations induced by
      evanescent diffraction modulate the specular reflection intensity, showing high
      intensity modulations. This will potentially allow implementation of subsurface
      crystal characterization using, for instance, a laboratory-scale X-ray
      diffractometer.

PMID- 30182942
TI  - Application of differential resonant high-energy X-ray diffraction to three
      dimensional structure studies of nanosized materials: A case study of Pt-Pd
      nanoalloy catalysts.
AB  - Atoms in many of the increasingly complex nanosized materials of interest to
      science and technology do not necessarily occupy the vertices of Bravais
      lattices. The atomic scale structure of such materials is difficult to determine
      by traditional X-ray diffraction and so their functional properties remain
      difficult to optimize by rational design. Here, the three-dimensional structure
      of PtxPd100-x nanoalloy particles is determined, where x = 0, 14, 36, 47, 64 and
      100, by a non-traditional technique involving differential resonant high-energy X
      ray diffraction experiments conducted at the K edge of Pt and Pd. The technique
      is coupled with three-dimensional modeling guided by the experimental total and
      element-specific atomic pair distribution functions. Furthermore, using DFT
      (density functional theory) calculation based on the positions of atoms in the
      obtained three-dimensional structure models, the catalytic performance of Pt-Pd
      particles is explained. Thus, differential resonant high-energy X-ray diffraction
      is shown to be an excellent tool for three-dimensional structure studies of
      nanosized materials. The experimental and modeling procedures are described in
      good detail, to facilitate their wider usage.

PMID- 30182943
TI  - X-ray reflectivity of chemically vapor-deposited diamond single crystals in the
      Laue geometry.
AB  - The absolute X-ray reflectivity of chemically vapor-deposited (CVD) single
      crystal diamond plates was measured in the Laue geometry in the double-crystal
      non-dispersive setting with an asymmetric Si beam-conditioner crystal. The
      measurements were supplemented by rocking-curve topography. The measured
      reflectivity curves are examined in the framework of the Darwin-Hamilton approach
      using a set of two independent parameters: the characteristic thickness of mosaic
      blocks and their average angular misorientation. Owing to strong extinction
      effects, the width of the reflectivity curves does not directly represent the
      average misorientation of the blocks. Two different sets of parameters were found
      for the 111 asymmetric reflection in the two different scattering configurations
      (beam compression and beam expansion). Analysis of the rocking-curve topographs
      shows that this discrepancy can be attributed to inhomogeneity of the diamond
      crystal microstructure.

PMID- 30182944
TI  - Energy flow of Bloch waves in X-ray dynamical diffraction in the Laue case for
      perfect crystals.
AB  - The direction of energy flow for Bloch waves during X-ray dynamical diffraction
      in perfect crystals is investigated. The energy flow is spread uniformly within
      the Borrmann fan in the conventional Laue case where the imaginary part of the
      crystal structure factor is much smaller than the real part. However, when the
      imaginary part is large, as in the case of X-rays with energies close to the
      absorption edge for single atoms in crystals, the energy flow direction is found
      to be restricted, and the results are discussed in relation to the Bragg case.

PMID- 30182945
TI  - The real part of the dispersion surface in X-ray dynamical diffraction in the
      Laue case for perfect crystals.
AB  - The real part of the dispersion surface in X-ray dynamical diffraction in the
      Laue case for perfect crystals is analysed using a Riemann surface. In the
      conventional two-beam approximation, each branch or wing of the dispersion
      surface is specified by one sheet of the Riemann surface. The characteristic
      features of the dispersion surface are analytically revealed using four
      parameters, which are the real and imaginary parts of two quantities that specify
      the degree of departure from the exact Bragg condition and the reflection
      strength. The present analytical method is generally applicable, irrespective of
      the magnitudes of the parameters with no approximation. Characteristic features
      of the dispersion surface are also revealed by geometrical considerations with
      respect to the Riemann surface.

PMID- 30182946
TI  - Experimental and theoretical investigations of an X-ray LLL interferometer with a
      wedge-shaped mirror plate.
AB  - An X-ray LLL interferometer with a wedge-shaped mirror plate is experimentally
      and theoretically investigated. Experimentally obtained interference patterns
      show that the Moire fringes are superposed on Pendellosung fringes and the period
      of the Pendellosung fringes is not changed after passing the analyzer plate. An
      eikonal theory of interference-fringe formation in an LLL interferometer with a
      wedge-shaped mirror plate is developed, and provides predictions that coincide
      with experimentally obtained results.

PMID- 30182947
TI  - Vertex collisions in 3-periodic nets of genus 4.
AB  - Unstable nets, by definition, display vertex collisions in any barycentric
      representation, among which are approximate models for the associated crystal
      structures. This means that different vertex lattices happen to superimpose when
      every vertex of a periodic net is located at the centre of gravity of its first
      neighbours. Non-crystallographic nets are known to be unstable, but
      crystallographic nets can also be unstable and general conditions for instability
      are not known. Moreover, examples of unstable nets are still scarce. This article
      presents a systematic analysis of unstable 3-periodic nets of genus 4, satisfying
      the restrictions that, in a suitable basis, (i) their labelled quotient graph
      contains a spanning tree with zero voltage and (ii) voltage coordinates belong to
      the set {-1, 0, 1}. These nets have been defined by a unique circuit of null
      voltage in the quotient graph. They have been characterized through a shortest
      path between colliding vertices. The quotient graph and the nature of the net
      obtained after identification of colliding vertices, if known, are also provided.
      The complete list of the respective unstable nets, with a detailed description of
      the results, can be found in the supporting information.

PMID- 30182948
TI  - Intensive X-ray standing-wave-like fields localized near a surface of a
      crystalline superlattice.
AB  - A peculiar kind of intensive X-ray standing wave is analytically shown to exist.
      Such an X-ray interference field is localized in the vicinity of a surface of a
      crystalline superlattice and its amplitude decays exponentially in both
      directions perpendicular to the surface. The appearance of the standing wave is
      accompanied by a deep dip in a chosen Bragg peak of the superlattice.

PMID- 30182949
TI  - Calculation of absorption and secondary scattering of X-rays by spherical
      amorphous materials in an asymmetric transmission geometry. Corrigendum.
AB  - A revised version of Table 2 of Bendert et al. [Acta Cryst. (2013). A69, 131-139]
      is provided.

PMID- 30182952
TI  - Astigmatism-reduced spherical concave grating holographically recorded by a
      cylindrical wave and a plane wave for Rowland circle mounting.
AB  - We propose a new recording system that employs a cylindrical wave and a plane
      wave to holographically record astigmatism-reduced Rowland-circle spherical
      gratings. We find that the astigmatism of the grating can be sharply reduced, so
      that the spectral intensity is improved. Meanwhile, its defocus aberration and
      meridional coma remain zero throughout the working spectrum, meaning the spectral
      resolution is similar to that of a conventional grating recorded by symmetric
      dual plane waves. We designed and made one astigmatism-reduced grating and one
      conventional grating for an actual Rowland-circle spherical-grating spectrometer.
      Our experimental results showed that the spectral intensity of the astigmatism
      reduced grating is about five times that of the conventional grating, while the
      resolution of the astigmatism-reduced grating is close to that of the
      conventional grating.

PMID- 30182951
TI  - Calycosin, a Phytoestrogen Isoflavone, Induces Apoptosis of Estrogen Receptor
      Positive MG-63 Osteosarcoma Cells via the Phosphatidylinositol 3-Kinase
      (PI3K)/AKT/Mammalian Target of Rapamycin (mTOR) Pathway.
AB  - BACKGROUND Osteosarcoma is the most common primary bone malignancy and often
      presents at an early age. Calycosin is a phytoestrogen isoflavone, which has
      previously been reported to inhibit tumor cell growth. The aim of this study was
      to investigate the effects of calycosin on apoptosis of estrogen receptor (ER)
      positive and ER-negative human osteosarcoma cell lines and tumor xenografts in
      mice. MATERIAL AND METHODS Cultured ER-positive MG-63 human osteosarcoma cells
      and ER-negative U2-OS human osteosarcoma cells were treated with increasing doses
      of calycosin (0, 25, 50, and 100 MUm). Cell viability and apoptosis were studied
      by an MTT assay and flow cytometry. Western blot measured the expression levels
      of the apoptosis-related protein p-PI3K, p-Akt, and p-mTOR in MG-63 cells, with
      and without pretreatment with the PI3K inhibitor, LY294002, the AKT inhibitor, MK
      2206, or the mTOR inhibitor, rapamycin. MG-63 tumor-bearing nude mice were used
      to evaluate the effects of treatment with calycosin. RESULTS Calycosin treatment
      inhibited proliferation and induced apoptosis in MG-63 cells, but had no effect
      on U2-0S cells. In MG-63 cells, calycosin treatment increased the expression of
      the PI3K/AKT/mTOR pathway proteins; inhibitor assays showed that expression of
      the PI3K protein was most strongly associated with the antitumor effects of
      calycosin. In the nude mouse MG-63 tumor xenografts, calycosin inhibited tumor
      growth and regulated the expression levels of apoptosis-related PI3K/AKT/mTOR
      pathway proteins. CONCLUSIONS The phytoestrogen, calycosin, induced apoptosis of
      cells of the ER-positive osteosarcoma cell line, MG-63, via the PI3K/AKT/mTOR
      pathway, with these effects being mainly due to PI3K.

PMID- 30182953
TI  - High-performance sensor achieved by hybrid guide-mode resonance/surface plasmon
      resonance platform.
AB  - We perform a comprehensive analysis of multiband absorption properties in a metal
      dielectric-metal-dielectric (MDMD) nanostructure under TM wave illumination. The
      multiband absorption can be attributed to the hybridization of the surface
      plasmon resonance (SPR) and the guide-mode resonance (GMR), and we identify the
      hybrid GMR/SPR by the dispersion relation equations of the SPR and GMR,
      respectively. More importantly, the MDMD nanostructure is very sensitive to the
      change of the dielectric environment for the special hybrid structure; thus, it
      can function as a good candidate for ultrasensitive biochemical sensing. The
      highest sensitivity of the MDMD nanostructure reaches 1087 nm/RIU with the figure
      of merit (FoM) of 23 and the new figure of merit (FoM*) of 483; it is performed
      by the absorption peak at 1796.1 nm of the double surface plasmon polariton with
      the strongest field enhancement at the surface.

PMID- 30182954
TI  - Effect of sensor SNR and extinction ratio on polarimetric imaging error for
      nanowire-based systems.
AB  - High-sensor SNR and high extinction ratio (ER), which are often contradictory
      requirements for nanowire-filter-based polarimetric imaging systems, aid in
      attenuating polarimetric imaging system errors. Expressions were derived to
      analyze their attenuation effects and then simplified using photoelectronic
      numbers received by superpixels (PNRS). The first-derivative ratios of PNRS and
      ER were calculated to compare their attenuation effects. Mathematical models and
      experiments conducted using polarimetric imaging systems with various ERs and
      PNRSs indicate that systems with low PNRS and high ER exhibit a polarization
      error affected more by the attenuation effect of the PNRS than that of the ER.
      When the system ER is higher than 28, the attenuation effect of the PNRS is
      higher than that of the ER. Thus, system error attenuation is a trade-off between
      sensor SNR and ER.

PMID- 30182955
TI  - Investigation of multiple laser shock peening on the mechanical property and
      corrosion resistance of shipbuilding 5083Al alloy under a simulated seawater
      environment: publisher's note.
AB  - This publisher's note corrects the labeling of Figs. 10-13 in Appl. Opt.57, 6300
      (2018)APOPAI0003-693510.1364/AO.57.006300.

PMID- 30182956
TI  - Deformations of circularly polarized Bessel vortex beam reflected and transmitted
      by a uniaxial anisotropic slab.
AB  - Bessel vortex beams are widely studied, since their intensity is independent of
      the propagation distance, and also their original field intensity distribution
      can be reconstructed after passing through an obstacle. Therefore, such beams are
      more advantageous for long-distance communication, optical imaging, and other
      potential applications. Based on the expansion of electromagnetic fields in terms
      of vector wave functions, in this investigation a method has been proposed to
      study the reflection and transmission of an incident circularly polarized Bessel
      vortex beam by a uniaxial anisotropic slab. The expansion coefficients of a
      circularly polarized Bessel vortex beam are derived by use of the cylindrical
      vector wave functions. The magnitude profiles of the electric field amplitude and
      phase, as well as the distribution of orbital angular momentum (OAM) states for
      both the reflected and transmitted beams, are numerically simulated and
      discussed. The effects of dielectric tensor and incident angle on the propagation
      characteristics of a circularly polarized Bessel vortex beam are analyzed. The
      observed results indicate that the contours of the electric field components
      cannot retain circularly symmetric structures; the distortion of phase
      distribution is obvious, and except for the predominant OAM state, other OAM
      states are derived, particularly for the reflected beam. Although few OAM states
      emerge in the transmitted beam, the predominant OAM state is still the same as
      that of the incident Bessel vortex beam.

PMID- 30182957
TI  - Advances and challenges of intraocular lens design [Invited].
AB  - Phacoemulsification technique with intraocular lens implantation has been a
      common treatment for cataract patients. With rising demand among the public, new
      technologies for lens design have emerged to minimize intraocular aberrations,
      improving visual quality to the largest extent. This paper systematically reviews
      the development of materials applied in lens manufacturing, the different
      categories of intraocular lenses, and respective design principles. The
      advantages and potential drawbacks of intraocular lenses are illustrated in the
      paper, and prospective research to improve the design are presented in the end.

PMID- 30182958
TI  - Characterization of an amplified piezoelectric actuator for multiple reference
      optical coherence tomography: erratum.
AB  - This erratum is submitted to correct information regarding Fig. 8 of Appl.
      Opt.57, E142 (2018)APOPAI0003-693510.1364/AO.57.00E142.

PMID- 30182959
TI  - Performance investigation of the polar coded FSO communication system over
      turbulence channel.
AB  - In this paper, for the first time, to the best of our knowledge, polar codes are
      introduced and experimentally implemented in a free space optical (FSO)
      communication system to combat atmospheric turbulence induced fading. By
      analyzing the characteristics of the turbulence channel, a method of evaluating
      the channel state information for polar decoding is proposed that can achieve
      good trade-off between the performance and the computational complexity of this
      polar coded system. To verify our scheme, an intensity modulation direct
      detection FSO communication experimental platform with a turbulence chamber is
      established. For the weak turbulence condition, comparing with the low-density
      parity check codes, the experimental results show that our proposed scheme has
      stronger error correcting capacity and lower computational complexity in
      combating the turbulence induced fading. Moreover, for moderate and strong
      turbulence conditions, the gamma-gamma turbulence model is adopted for
      constructing the Monte Carlo simulation. The results of the experiment and
      simulation both show that our proposed scheme can effectively combat atmospheric
      turbulence induced fading with a relatively low computational complexity in a
      wide range of turbulence conditions.

PMID- 30182960
TI  - Influence of self- and cross-phase modulations on an optical frequency doubling
      process for metamaterials.
AB  - In the process of doubling the frequency of high-power laser radiation in
      metamaterials, the self- and cross-phase modulations associated with the cubic
      nonlinearity of the medium are studied in the constant-intensity approximation.
      It is assumed that the pump wave propagates in a region with negative refraction.
      It is shown that in the case of a nonlinear-optical process of frequency doubling
      of an intense light wave in a metamaterial, it is important to take into account
      the self-action and cross-interaction effects that directly affect the optimal
      phase relationship between the interacting waves. It is discovered that, as a
      result of counter interaction of waves, the period of spatial beats changes.
      According to the analytic expressions obtained in the work, the choice of optimal
      parameters of the problem makes it possible to realize the regime of effective
      frequency doubling. By varying the intensity of the pump, it is possible to
      control and manipulate the intensity of the output coherent radiation from the
      minimum to the maximum value. A numerical evaluation of the efficiency of the
      doubling process in a metamaterial is given, and a comparison is made with
      similar results in LiNbO3 and KDP crystals. It is demonstrated that the effects
      of self- and cross-modulation in media with negative refraction can be used as a
      powerful tool for developing effective frequency doublers in such materials.

PMID- 30182961
TI  - Fiber optic gyroscope noise reduction with fiber ring resonator.
AB  - A method of improving the angular random walk (ARW) of a fiber optic gyroscope
      (FOG) using a fiber ring resonator (FRR) to reduce the relative intensity noise
      (RIN) is demonstrated. An FRR reduces the RIN near the proper frequency and
      improves the ARW. The analytical forms for the RIN transfer function and the
      power transmission of the FRR are derived when the free spectral range of the FRR
      is much narrower than the source bandwidth. Building the FRR using couplers and
      fiber with low excess loss enhances the RIN reduction. For the coupling ratios,
      there is a trade-off between the RIN reduction and the power transmission. The
      coupling ratios are 90%-10% tap in the experiment. When the FRR resonator length
      is shorter than the FOG coil length, the ARW improvement is further enhanced by
      adjusting the average window length in the signal processing. An experiment
      demonstrated a 7 dB decrease in the RIN at the loop proper frequency, which
      reduces the standard deviation by 3.5 dB. The ARW was reduced from 970 to 570 
      MUdeg/h1/2, which amounts to a 2.3 dB reduction.

PMID- 30182962
TI  - Photonic generation of microwave waveforms based on a dual-polarization
      quadrature phase-shift-keying modulator.
AB  - A novel microwave waveform generator based on a dual-polarization quadrature
      phase-shift-keying (DP-QPSK) modulator is proposed and experimentally
      demonstrated in this paper. The X-QPSK modulator is modulated by a local
      oscillator signal. For XI Mach-Zehnder modulator (MZM), odd sidebands are
      eliminated; for XQ-MZM, even sidebands are eliminated, while the Y-QPSK modulator
      is not modulated. Triangular or square waveforms can be generated by biasing the
      X-QPSK and adjusting the polarization controller properly. 3 GHz and 6 GHz
      triangular and square waveforms are successfully generated by experiment. The
      scheme does not need a high modulation index (m=1.25 in this paper). In addition,
      it features low cost and a simple structure without a filter or phase shifter.

PMID- 30182963
TI  - Design of ultracompact tunable fractional-order temporal differentiators based on
      hybrid-plasmonic phase-shifted Bragg gratings.
AB  - The design and the simulation of tunable fractional-order temporal
      differentiators based on Si-hybrid plasmonic phase-shifted Bragg gratings are
      proposed in this paper, where strong light confinement in the hybrid plasmonic
      waveguide is employed to significantly reduce the overall length of the
      differentiators. According to 2D- and 3D-FDTD simulation results, the proposed
      structures with overall lengths of less than 8 MUm can provide arbitrary
      differentiation order and differentiation bandwidths as high as 1.6 THz. The
      differentiation order and the bandwidth of the proposed structures can be tuned
      in relatively wide ranges by changing the geometrical parameters of the
      structures. For example, the differentiation order can be changed from 0.57 to
      0.97 by changing the number of the Bragg grating periods in a 3D differentiator
      structure. Furthermore, it is shown that using an electro-optical polymer as the
      low-index material of the hybrid plasmonic waveguide, the differentiation order
      and the central frequency of the proposed differentiators can be actively tuned
      through applying a proper actuating electrical field (voltage) to the structure.
      This property, along with the ultracompact footprint and wide bandwidth of the
      proposed differentiators, suggest their application in ultrafast all-optical
      signal-processing systems.

PMID- 30182964
TI  - All-PM wavelength-tunable and harmonically mode-locking Yb-doped fiber laser.
AB  - We report a wavelength-tunable harmonically mode-locking dissipative soliton
      fiber laser based on a high-speed intensity modulator with a simple all
      polarization-maintaining (all-PM) cavity. The center wavelength can be precisely
      tuned from 1029.35 to 1079.25 nm by tuning only the frequency of the pulse
      pattern generator (PPG), and the linear tuning accuracy of the wavelength can
      reach 0.0093 nm/kHz. The degree of polarization can reach 98.969%. The FWHM of
      the pulse is measured to be 30.1 ps, and the intracavity pulse energy after the
      gain fiber can reach 5.41 nJ. All orders of the harmonic mode-locking repetition
      rate are tuned from ~33.346 to ~366.806  MHz through adjustment of the data
      length and frequency of PPG.

PMID- 30182965
TI  - Quantum lidar based on a random interleaved optical pulse sequence consisting of
      wavelength-time quantum states.
AB  - Based on a random interleaved optical pulse sequence consisting of wavelength
      time quantum states, we have established a quantum lidar model. Multiple quantum
      states are used as a detection tool for the interception and interference of a
      target, and multiple wavelengths spanning the ultraviolet to near-infrared
      waveband are used to avoid interference and improve the detection efficiency. We
      elaborate upon the working principle of the entire quantum lidar detection system
      and demonstrate its feasibility through simulations, thereby establishing a
      foundation for the application of quantum lidar systems aboard satellite
      platforms at long distances from the high-precision detection of targets.

PMID- 30182966
TI  - Slowing designer surface plasmons in a surface-wave photonic crystal.
AB  - We propose and experimentally demonstrate a broadband slow-wave system in a
      surface-wave photonic crystal based on a non-uniform line-defect waveguide with
      graded metallic pillars, whose dispersions and cutoff frequencies vary gradually
      along the waveguide. Since the group velocity of designer surface plasmons at the
      cutoff frequencies is zero, we show that surface waves can be slowed and stopped
      at different positions under different frequencies. Experimental evidence
      including transmission measurements and direct near-field profile imaging
      performed in the microwave frequencies validate the stopping of surface waves in
      a broadband range within the forbidden bandgap of the surface-wave photonic
      crystal. This proposal is a promising candidate for slow-wave devices implemented
      on a single metal surface in both the microwave and terahertz frequency ranges.

PMID- 30182967
TI  - Efficient hybrid method for electromagnetic scattering from a coated object above
      a two-layered rough surface.
AB  - A powerful and efficient hybrid method combining the finite-element boundary
      integral method with fast multipole method (FE-BI-FMM) is proposed in this paper
      to study the electromagnetic scattering characteristics from a coated object
      above a two-layered dielectric rough surface. The finite-element method (FEM) is
      applied to model the scattering from the coated object, and multiple interactions
      between the object and layered rough surface are handled by the FMM-enhanced
      boundary integral method (BIM). A hybrid solver is adopted to efficiently solve
      the FEM-BIM matrix equation. Several numerical results are presented, and the
      influence of several parameters of the composite model on the scattering
      characteristics is analyzed in detail. Both vertical and horizontal polarizations
      for the incident waves are considered.

PMID- 30182968
TI  - Compact echelle spectrometer employing a cross-grating.
AB  - The concept and the implementation of a compact and simplified echelle
      spectrometer are presented, and the working principle is demonstrated by first
      experimental measurements. The crucial element of the setup is a cross-grating,
      combining an echelle grating utilizing several higher diffraction orders (5th up
      to 11th) and a superposed perpendicular-oriented cross-dispersing grating. Two
      alternative manufacturing approaches for the cross-grating are presented and
      discussed. The first approach combines Talbot lithography for the deep echelle
      grating and interference lithography for the cross-dispersing structure. As a
      second approach, direct laser-beam writing was applied. The compact echelle
      spectrometer covers a spectral range from 380 to 700 nm and offers a spectral
      resolution of ~2  nm.

PMID- 30182969
TI  - Compact, fiber-coupled, single-ended laser-absorption-spectroscopy sensors for
      high-temperature environments.
AB  - The design and demonstration of a compact single-ended laser-absorption
      spectroscopy sensor for measuring temperature and H2O in high-temperature
      combustion gases is presented. The primary novelty of this work lies in the
      design, demonstration, and evaluation of a sensor architecture that uses a single
      lens to provide single-ended, alignment-free (after initial assembly)
      measurements of gas properties in a combustor without windows. We demonstrate
      that the sensor is capable of sustaining operation at temperatures up to at least
      625 K and is capable of withstanding direct exposure to high-temperature (~1000 
      K) flame gases for long durations (at least 30 min) without compromising
      measurement quality. The sensor employs a fiber bundle and a 6 mm diameter
      antireflection-coated lens mounted in a 1/8'' NPT-threaded stainless-steel body
      to collect laser light that is backscattered off native surfaces. Distributed
      feedback tunable diode lasers (TDLs) with a wavelength near 1392 nm and 1343 nm
      were used to interrogate well-characterized H2O absorption transitions using
      wavelength-modulation-spectroscopy techniques. The sensor was demonstrated with
      measurements of gas temperature and H2O mole fraction in a propane-air burner
      with a measurement bandwidth up to 25 kHz. In addition, this work presents an
      improved wavelength-modulation spectroscopy spectral-fitting technique that
      reduces computational time by a factor of 100 compared to previously developed
      techniques.

PMID- 30182970
TI  - Astigmatism and deformation correction for a holographic head-mounted display
      with a wedge-shaped holographic waveguide.
AB  - In this study, a head-mounted display (HMD) system based on a wedge-shaped
      holographic waveguide that can present holographic virtual images with tunable
      distance is achieved. The compact computer-generated-hologram system using a
      spatial light modulator was employed to offer the dynamic image, where the probe
      beam for the hologram reconstruction is a convergent wave, and the DC term of the
      diffraction wave can be blocked by a barrier. The wedge-shaped holographic
      waveguide element was used as the combiner of the HMD system to generate a
      compact structure. A wedge with a polished surface was designed for in-coupling
      the image into the waveguide, and a reflection-type holographic optical element
      (HOE) was used for out-coupling the image from the waveguide. The astigmatism
      aberration and deformation of the diffraction images at various distances are
      analyzed and then are compensated. Finally, the virtual image can be obtained
      without aberration with experimental verification.

PMID- 30182971
TI  - Signal detection algorithms for interferometric sensors with harmonic phase
      modulation: miscalibration of modulation parameters.
AB  - In the current paper, we have developed an analytical apparatus that allows us to
      calculate the phase error produced by miscalibration of modulation parameters.
      The case of harmonic modulation is considered, and the analysis is performed for
      cases of miscalibration for two parameters: amplitude and start phase. Two
      demodulation algorithms are considered: a conventional 4-point algorithm, based
      on an ordinary least-squares approach, and a previously developed 4+1 algorithm
      with high immunity to phase error, induced by change of target phase on the
      demodulation interval. Predictions, given by developed analytical equations, are
      verified by means of numeric modeling.

PMID- 30182972
TI  - Analytical-performance improvement of aqueous solution by chemical replacement
      combined with surface-enhanced laser-induced breakdown spectroscopy.
AB  - In this study, chemical replacement combined with surface-enhanced laser-induced
      breakdown spectroscopy (CR-SENLIBS) was introduced for detecting the trace
      chromium (Cr) element in an aqueous solution, which could use chemical
      replacement to change the sample from liquid to solid. In order to illustrate the
      analytical-performance of the CR-SENLIBS, the direct analysis of the liquid
      surface by LIBS (LSLIBS) was investigated for comparison. The results show that
      the spectral intensity of Cr I 357.86 nm, plasma lifetime, and spectral stability
      were improved. Moreover, the limit of detection of Cr I 357.86 nm was 0.018
      MUg/mL, which was lower than 1.814 MUg/mL for LSLIBS. Furthermore, the accuracy
      and precision were improved more than 60% and 80%, respectively; for example, the
      root-mean-square error of cross-validation was improved from 1.09 to 0.75 MUg/mL,
      and the average relative standard deviation of the predicted concentration of Cr
      was reduced from 22.89% to 4.53% by using CR-SENLIBS. These results suggest that
      CR-SENLIBS has good analytical-performance, which exhibits great potential in
      water quality monitoring.

PMID- 30182973
TI  - Wavefront prediction with reservoir computing for minimizing the effects of
      angular anisoplanatism.
AB  - Supervised learning with recurrent neural networks has been used to estimate
      perturbations that adversely affect image quality of natural guide stars due to
      atmospheric turbulence. While this method has been shown to be effective for
      generating spatially variant point spread functions (PSFs) for image
      reconstruction using low-turbulence models, recent extensions to these methods,
      facilitated by enhancements to optimize network parameters, show potential to
      extend this method to moderate-turbulence multilayer models. In this paper,
      spatio-temporal learning using reservoir computing, a discriminative learning
      method known as an echo state network, is proposed to estimate the spatially
      variant PSF, thus allowing for improved image restoration of point-source exo
      atmospheric objects outside the isoplanatic patch. The forward problem is
      modelled by training a reservoir computer with time-series perturbations from
      three or more natural guide stars. Known site profile data is incorporated to
      optimize the model for training, where perturbations under similar conditions are
      used to test estimated aberrations over a wide, anisoplanatic field.

PMID- 30182974
TI  - Distinctive roles of elevated absorbing aerosol layers on free-space optical
      communication systems.
AB  - The impact of enhanced local heating due to absorption of solar radiation by
      elevated layers of aerosol black carbon (BC) in the lower troposphere in the
      performance of free-space optical (FSO) communication links is investigated. It
      is seen that a strong elevated BC layer at an altitude around 4.5 km enhances the
      atmospheric stability locally and leads to a large reduction in the atmospheric
      refractive index structure parameter (Cn2), leading to improved performance of
      the FSO communication links. For layers in the tropical atmosphere with
      sufficiently high BC concentration, the signal attenuation due to BC absorption
      is alleviated by the large reduction in Cn2 due to BC-induced warming and brings
      down the link outage probability. Synergy between reduction in Cn2 and long
      wavelength transmission improves the link budget significantly by reducing the
      beam wander and number of adaptive optics units required.

PMID- 30182975
TI  - Improvement of printing efficiency in holographic stereogram printing with the
      combination of a field lens and holographic diffuser.
AB  - In this paper, we use a field lens and a holographic diffuser together to improve
      the printing efficiency of a holographic stereogram printing system based on the
      effective perspective images' segmentation and mosaicking method. The light rays'
      regulation function of the field lens and the modulation function of the
      holographic diffuser are analyzed. Holographic diffusers with different expanding
      angles are optimized by numerical simulations and verified by optical
      experiments. We can achieve a better holographic stereogram reconstruction effect
      as well as a better printing efficiency when adopting a field lens and a 10
      degrees  holographic diffuser together. With the proposed method, the energy
      efficiency can be improved, and the printing time can be reduced greatly.

PMID- 30182976
TI  - Propagation and asymmetric behavior of optical pulses through time-dynamic loss
      gain-assisted media.
AB  - We report an asymmetric behavior of optical pulses during their propagation
      through a time-varying linear optical medium. The refractive index of the medium
      is considered to be varying with time and complex, such that a sufficient amount
      of gain and loss is present to realize their effect on pulse propagation. We have
      exploited the universal formula for optical fields in time-varying media.
      Numerically simulated results reveal that pulses undergo opposite temporal shifts
      around their initial center position during their bi-directional propagation
      through the medium along with corresponding spectral shifts. Moreover, the peak
      power and accumulated chirp (time derivative of accumulated phase) of the output
      pulse in both propagation directions are also opposite in nature, irrespective of
      their initial state. Numerically simulated behavior of the pulses agrees well
      with the analytical solutions.

PMID- 30182977
TI  - Improved analysis model for material removal mechanisms of bonnet polishing
      incorporating the pad wear effect.
AB  - Bonnet polishing technology has been widely applied in precision optical
      machining. Until now, most of the research concerning the modeling for material
      removal mechanisms of bonnet polishing have been presented based on the well
      known Preston model. However, the various parameters involved in the bonnet
      polishing process are not formulated into that model, such as slurry
      characteristics, pad properties, bonnet sizes, processing conditions, etc.
      Recently, several analysis models capturing those various parameters have been
      developed and are even capable of interpreting non-Prestonian behaviors, but the
      pad wear effect has still not been taken into account. Hence, the purpose of this
      paper is to establish an improved analysis model by incorporating the pad wear
      effect with the cumulative polishing time. Compared with the previous analysis
      model and Preston model, the predicted results of the improved analysis model are
      much closer to the experimental data and become more acceptable. According to the
      analysis of key parameters, the understanding of material removal mechanisms in
      bonnet polishing is further completed, and the time-dependent pad wear effect
      should no longer be neglected.

PMID- 30182978
TI  - Iterative phase retrieval in coherent diffractive imaging: practical issues.
AB  - In this work, issues in phase retrieval in the coherent diffractive imaging (CDI)
      technique, from discussion on parameters for setting up a CDI experiment to
      evaluation of the goodness of the final reconstruction, are discussed. The
      distribution of objects under study by CDI often cannot be cross-validated by
      another imaging technique. It is therefore important to make sure that the
      developed CDI procedure delivers an artifact-free object reconstruction. Critical
      issues that can lead to artifacts are presented and recipes on how to avoid them
      are provided.

PMID- 30182979
TI  - Bidirectional mode-locked thulium-doped fiber laser.
AB  - We report a bidirectional mode-locked thulium-doped fiber laser. Mode-locking is
      enabled by the combination of semiconductor saturable absorption and nonlinear
      polarization rotation. Two stable mode-locked picosecond pulse trains in opposite
      directions are generated with a fundamental repetition rate of ~16.57  MHz.
      Output wavelengths are tunable over 35 nm.

PMID- 30182980
TI  - First industrial-grade coherent fiber link for optical frequency standard
      dissemination.
AB  - We report on a fully bidirectional 680 km fiber link connecting two cities for
      which the equipment, the setup, and the characterization are managed for the
      first time by an industrial consortium. The link uses an active telecommunication
      fiber network with parallel data traffic and is equipped with three repeater
      laser stations and four remote double bidirectional erbium-doped fiber
      amplifiers. We report a short-term stability at 1 s integration time of 5.4*10-16
      in 0.5 Hz bandwidth and a long-term stability of 1.7*10-20 at 65,000 s of
      integration time. The accuracy of the frequency transfer is evaluated as 3*10-20.
      No shift is observed within the statistical uncertainty. We show a continuous
      operation over five days with an uptime of 99.93%. This performance is comparable
      with the state-of-the-art coherent links established by National Metrology
      Institutes in Europe. It is a first step in the construction of an optical fiber
      network for metrology in France, which will give access to an ultrahigh
      performance frequency standard to a wide community of scientific users.

PMID- 30182981
TI  - Preliminary measurements of fluorescent aerosol number concentrations using a
      laser-induced fluorescence lidar.
AB  - A laser-induced fluorescence lidar has been developed for detecting the
      concentration of fluorescent aerosols in the air. The fluorescence lidar was
      constructed with a pulsed fourth-harmonic Nd:YAG laser at the ultraviolet
      wavelength of 266 nm with a repetition rate of 10 Hz. A 250 mm diameter custom
      telescope was used to collect optical spectra ranging from 260 to 560 nm.
      Fluorescence signals with wavelengths ranging from 310-440 nm were extracted,
      exploring a filter with a bandwidth of 130 nm. The preliminary experiments were
      conducted at the campus of Xi'an University of Technology, in which the
      fluorescence signals of atmospheric fluorescent aerosols were continuously
      collected from 20:00 to 23:00 CST on 13 December 2017. Based on the fluorescence
      lidar equation, the density of fluorescence signals was calibrated using Rayleigh
      Mie scattering signals and ozone (O3) concentration data at the ground level.
      Measured ranges show a strong dependence with the O3 concentrations due to its
      absorption characteristics at ultraviolet 266 nm. Moreover, the concentration of
      the biogenic particles was also calculated based on the raw data of the
      fluorescence channel. Obtained results show that the concentration of biogenic
      particles in the Xi'an area varied greatly, ranging from 3456 particles . m-3 to
      8835 particles . m-3 during winter.

PMID- 30182982
TI  - How light absorption modifies the radiative force on a microparticle in optical
      tweezers.
AB  - Reflection and refraction of light can be used to trap small dielectric particles
      in the geometrical optics regime. Absorption of light is usually neglected in
      theoretical calculations, but it is known that it occurs in the optical trapping
      of semi-transparent particles. Here, we propose a generalization of Ashkin's
      model for the radiative force exerted on a spherical bead, including the
      contribution due to attenuation/absorption of light in the bulk of the particle.
      We discuss in detail the balance between refraction, reflection, and absorption
      for different optical parameters and particle sizes. Our findings contribute to
      the understanding of optical trapping of light-absorbing particles and may be
      used to predict whenever absorption is important in real experiments.

PMID- 30182983
TI  - Transformation algorithm and analysis of the Fourier transform spectrometer based
      on cascaded Fabry-Perot interferometers.
AB  - The Fourier transform spectrometer based on cascaded Fabry-Perot interferometers
      is analyzed, where one of the interferometers has a fixed length, while the other
      is scanning. We propose a method to reconstruct the spectrum correctly based on
      solving the integral equation of the overall response of the cascaded
      interferometers. The method is tested for different design parameters and noise
      conditions. Low reconstruction error below -80  dB is found to be achievable.

PMID- 30182984
TI  - Probing multipulse laser ablation by means of self-mixing interferometry.
AB  - In this work, self-mixing interferometry (SMI) is implemented inline to a laser
      microdrilling system to monitor the machining process by probing the ablation
      induced plume. An analytical model based on the Sedov-Taylor blast wave equation
      is developed for the expansion of the process plume under multiple-pulse laser
      percussion drilling conditions. Signals were acquired during laser microdrilling
      of blind holes on stainless steel, copper alloy, pure titanium, and titanium
      nitride ceramic coating. The maximum optical path difference was measured from
      the signals to estimate the refractive index changes. An amplitude coefficient
      was derived by fitting the analytical model to the measured optical path
      differences. The morphology of the drilled holes was investigated in terms of
      maximum hole depth and dross height. The results indicate that the SMI signal
      rises when the ablation process is dominated by vaporization, changing the
      refractive index of the processing zone significantly. Such ablation conditions
      correspond to limited formation of dross. The results imply that SMI can be used
      as a nonintrusive tool in laser micromachining applications for monitoring the
      process quality in an indirect way.

PMID- 30182985
TI  - Single-transverse-mode waveguide-coupled deformed hexagonal resonator
      microlasers.
AB  - AlGaInAs/InP waveguide-coupled deformed hexagonal resonator microlasers with
      enhanced mode quality (Q)-factors are demonstrated for realizing single
      transverse-mode operation. A circular hole is introduced to the center of the
      hexagonal resonators with rounded corners to enhance the mode Q-factors and
      suppress high-order transverse modes simultaneously. Single-mode lasing with side
      mode suppression ratios up to 40 dB is obtained for the 10-MUm-sidelength
      hexagonal microlasers with a center hole. All the lasing spectra demonstrate pure
      single-transverse-mode properties within the whole tuning range of injection
      current, and mode hopping with one, two, and three longitudinal-mode intervals is
      observed due to the mode Q-factor modification by the center holes. To further
      reduce the device size and threshold current, the deformed hexagonal resonator
      microlasers with the flat sides replaced by circular arcs are analyzed and
      demonstrated experimentally. The Q-factors of the fundamental transverse modes
      can be enhanced by two orders of magnitude due to the convergence effect of the
      circular sides by optimizing the deformation amplitude, while the single
      transverse-mode property is still maintained. A threshold current of 2.4 mA is
      realized for a circular-side hexagonal microlaser with the side length of 8.5 MUm
      and the deformation amplitude of 0.55 MUm.

PMID- 30182986
TI  - Adaptive dual-exposure fusion-based transport of intensity phase microscopy.
AB  - Via the transport of intensity phase microscopy, quantitative phase can be
      retrieved directly from captured multi-focal intensities. The accuracy of the
      retrieved phases depends highly on the quality of the recorded images; therefore,
      the exposure time should be carefully chosen for high-quality intensity captures.
      However, it is difficult to record well-exposure intensities to maintain rather a
      high signal to noise ratio and to avoid over-exposure due to the complex samples.
      In order to simplify the exposure determination, here the adaptive dual-exposure
      fusion-based transport of intensity phase microscopy is proposed: with captured
      short- and long-exposure images, the well-exposure multi-focal images can be
      numerically reconstructed, and then high-accurate phase can be computed from
      these reconstructed intensities. With both simulations and experiments provided
      in this paper, it is proved that the adaptive dual-exposure fusion-based
      transport of intensity phase microscopy not only provides numerically
      reconstructed well-exposure image with simple operation and fast speed but also
      extracts highly accurate retrieved phase. Moreover, the exposure time selection
      scope of the proposed method is much wider than that based on single exposure,
      and even though there is an over-exposure region in the long-exposure image, a
      well-exposure image can still be reconstructed with high precision. Considering
      its advantages of high accuracy, fast speed, simple operation, and wide
      application scope, the proposed technique can be adopted as quantitative phase
      microscopy for high-quality observations and measurements.

PMID- 30182987
TI  - Flame temperature estimation from light field image processing.
AB  - We propose a novel flame temperature estimation method based on a flame light
      field sectioned imaging model of complex temperature distribution in different
      media. The proposed method relies on multi-pixel reconstruction to improve the
      resolution of sub-aperture images. In addition, the wavelet transform denoises
      the flame refocused image, and then the Lucy-Richardson algorithm deconvolves the
      image. The temperature estimation accuracy using the proposed method is higher
      than that reported in a previous work, with a larger temperature estimation range
      from 1250 K to 1800 K. Moreover, we found that deconvolution plays an important
      role in determining the temperature estimation accuracy.

PMID- 30182988
TI  - Investigation of an apodized imaged Hartmann wavefront sensor.
AB  - Quantitative wavefront measurements are demonstrated using a Hartmann mask re
      imaged onto a camera. The wavefront is reconstructed using standard algorithms
      applied to the difference of beamlet centroids determined from fluence
      distributions obtained for two different longitudinal locations of the mask. The
      wavefront of the optical wave in the object plane is measured independently of
      imaging-system collimation. Apodization obtained with spatially dithered
      distributions of small transparent or opaque pixels improves the measurement
      accuracy by reducing the spatial-frequency content of the mask holes. Simulations
      and experiments demonstrate the excellent accuracy of this diagnostic over a wide
      range of parameters, making it suitable, for example, to characterize laser
      systems.

PMID- 30182989
TI  - Measured performance of shadow-cast coated gratings for spectro-polarimetric
      applications.
AB  - We measured the efficiency of a reflective echelle grating that was specially
      coated in order to reduce the polarization of the diffracted light. The standard
      coated grating can be used between approximately 350 and 1200 nm for diffraction
      orders between 14 and 5. In these orders, the standard grating can be strongly
      polarized (up to ~80%), which impacts its usability in spectro-polarimetric
      instruments. The adoption of the shadow-cast coating technique, which implies
      selectively depositing the reflective coating exclusively onto the blazed facets,
      can significantly reduce the polarization of the grating while preserving its
      average efficiency.

PMID- 30182990
TI  - Blood vessel segmentation of fundus images via cross-modality dictionary
      learning.
AB  - Automated retinal blood vessel segmentation is important for the early computer
      aided diagnosis of some ophthalmological diseases and cardiovascular disorders.
      Traditional supervised vessel segmentation methods are usually based on pixel
      classification, which categorizes all pixels into vessel and non-vessel pixels.
      In this paper, we propose a new retinal vessel segmentation method with the
      motivation to extract vessels based on vessel block segmentation via cross
      modality dictionary learning. For this, we first enhance the structural
      information of vessels using multi-scale filtering. Then, cross-modality
      description and segmentation dictionaries are learned to build the intrinsic
      relationship between the enhanced vessels and the labeled ground truth vessels
      for the purpose of vessel segmentation. Also, effective pre-processing and post
      processing are adopted to promote the performance. Experimental results on three
      benchmark data sets demonstrate that the proposed method can achieve good
      segmentation results.

PMID- 30182991
TI  - Fabrication of high fill factor cylindrical microlens array with isolated thermal
      reflow.
AB  - We demonstrate a simple, controllable, and stable method for fabricating high
      fill factor cylindrical microlens array with a novel isolated thermal reflow
      process. In this method, microstripes with a very small gap were obtained via
      digital micromirror device-based lithography, then covered with
      polydimethylsiloxane (PDMS) solution. The prepared microstripes were isolated and
      were heated and reflowed to a cylindrical microlens array. During the reflow
      process, the semicross-linked PDMS can serve as a barrier to prevent the diameter
      change and the bonding of adjacent microlenses. By this special treatment, the
      fill factor of the cylindrical microlens array can be significantly improved.
      Moreover, the reflow time and temperature have very little effect on the
      microlens shape due to the surrounded semicross-linked PDMS. This will make our
      process stabler than traditional methods. The measured 3D profile is good and
      satisfactory, and excellent optical performance is demonstrated with the
      fabricated cylindrical microlens arrays. The proposed method may offer a viable
      route for fabrication of high fill factor microlens arrays in a very simple and
      stable way.

PMID- 30182992
TI  - Review and accuracy comparison of various permittivity-averaging schemes for
      material discontinuities in the two-dimensional FDFD method: implementation using
      efficient computer graphics techniques.
AB  - Several known and widely used averaging techniques aiming to improve the accuracy
      of the two-dimensional finite-difference frequency-domain (FDFD) method, in the
      presence of material discontinuities, are reviewed, numerically tested, and
      compared with respect to their accuracies. Furthermore, all averaging techniques
      are rigorously and efficiently implemented using the Supercover Digital
      Differential Analyzer algorithm and a modified Liang-Barsky algorithm suitably
      adapted from computer graphics applications. The FDFD with Gaussian blurring; the
      FDFD with volume-polarized effective permittivity; the FDFD with volume-polarized
      effective permittivity on shifted cells; and the FDFD with anisotropic smoothing
      [FDFD (AS)] are compared with respect to their accuracies (for both TE and TM
      polarization), in the case of scattering by an infinite homogeneous cylinder (for
      which analytical solution exists) comprising a lossless dielectric, a high-index,
      low-loss dielectric, or a metal. Sample plots of the relative errors are
      presented for various field components. Absolute error norms (L2 and Linfinity)
      are also presented for both polarizations and for two grid-cell sizes for
      quantitative comparisons. The results show that the FDFD (AS) prevails in
      accuracy mainly because it satisfies the boundary conditions at the cylinder's
      boundary the best. However, for the high-index dielectrics and metals, even the
      FDFD without any averaging gives very good results for the field components
      parallel to the uniformity direction. However, the FDFD (AS) is always more
      accurate when the in-plane field components are sought.

PMID- 30182993
TI  - Fabrication of a laser cavity mirror in a large mode area fiber by an ultrashort
      pulse laser.
AB  - We present herein a method to fabricate a higher-order fiber grating (HOFG) for
      use as a fiber-cavity mirror in a fiber laser. The HOFG was fabricated by
      irradiating the Yb-doped large core of a double-clad fiber by a femtosecond
      pulsed laser. The HOFG served as a laser cavity mirror with a reflectance of
      13.2% and yielded a laser line with a spectral full width at half-maximum of 0.56
      nm.

PMID- 30182994
TI  - Analysis of interference fringes based on three circularly polarized beams
      targeted for birefringence distribution measurements.
AB  - As a potential means of measuring birefringence distribution, we analyzed the
      interference fringes based on three circularly polarized beams: a right-handed
      signal beam, a left-handed reference beam, and a right-handed reference beam. All
      beams were crossed at the same angle on the interfering plane, creating a two
      dimensional interference fringe with three grating vectors. We proposed that by
      analyzing the interference fringes, we can measure the anisotropic phase shift in
      the signal beam. The obtained features of the anisotropic phase shift can be
      extended to the measurement of two-dimensional birefringence distributions
      without rotational manipulations of the objectives or polarizers. The fringes
      were generated by monolithic gratings, which can generate three-beam interfering
      fields precisely and easily. Finally, we confirmed the feasibility of a
      birefringence measurement system without any rotational manipulations of optics.

PMID- 30182995
TI  - Enhanced light extraction of deep ultraviolet light-emitting diodes by using
      optimized aluminum reflector.
AB  - Deep ultraviolet light-emitting diodes (DUV-LEDs) have become a promising UV
      light source for sterilization, disinfection, and purification. However, the
      challenge in practical application of DUV-LEDs still remains in their low light
      efficiency. In this paper, we propose an optimized aluminum (Al) reflector for
      the light extraction enhancement of DUV-LEDs. The optical model of DUV-LEDs was
      established, and the optical simulations were performed to achieve the optimized
      reflector. The DUV-LEDs exhibit the highest light efficiency when the reflector
      has the optimized feature sizes with an angle of 60 degrees , a height of 2.0 mm,
      and an internal radius of 2.5 mm. Furthermore, the optimized reflector with
      different reflectance was fabricated and applied for the packaging of DUV-LEDs.
      Consequently, the light output powers of DUV-LEDs are enhanced by 28.8%, 37.0%,
      and 43.8%, respectively, by using the different reflectors at the driving current
      of 100 mA. It is attributed to the remarkable reflection effect of the Al
      reflector, which increases the light extraction of the sidewall emission from the
      DUV-LED chip.

PMID- 30182996
TI  - Scanning diffracted-light microscopy.
AB  - Scanning the direction of the light that is diffracted by a sample permits the
      achievement of image diversity, which is necessary for implementing the Fourier
      ptychographic microscopy technique (FPM) using only perpendicular illumination.
      We also demonstrated that the same method allows for implementation of the
      illumination-direction-multiplexing FPM technique when the sample is illuminated
      using a ring-shaped condenser.

PMID- 30182997
TI  - Tensor-based predictive control for extremely large-scale single conjugate
      adaptive optics.
AB  - In this paper we propose a data-driven predictive control algorithm for large
      scale single conjugate adaptive optics systems. At each time sample, the Shack
      Hartmann wavefront sensor signal sampled on a spatial grid of size N*N is
      reshuffled into a d-dimensional tensor. Its spatial-temporal dynamics are modeled
      with a d-dimensional autoregressive model of temporal order p, where each tensor
      storing past data undergoes a multilinear transformation by factor matrices of
      small sizes. Equivalently, the vector form of this autoregressive model features
      coefficient matrices parametrized with a sum of Kronecker products between d
      factor matrices. We propose an Alternating Least Squares algorithm for
      identifying the factor matrices from open-loop sensor data. When modeling each
      coefficient matrix with a sum of r terms, the computational complexity for
      updating the sensor prediction online reduces from O(pN4) in the unstructured
      matrix case to O(prd N2(d+1)d). Most importantly, this model structure breaks
      away from assuming any prior spatial-temporal coupling as it is discovered from
      the data. The algorithm is validated on a laboratory testbed that demonstrates
      the ability to accurately decompose the coefficient matrices of large-scale
      autoregressive models with a tensor-based representation, hence achieving high
      data compression rates and reducing the temporal error especially for a large
      Greenwood per sample frequency ratio.

PMID- 30182998
TI  - Bit error rate of pulse position modulated optical wireless communication links
      in oceanic turbulence.
AB  - The upper bound of the average bit error rate (BER) of a pulse position modulated
      (PPM) optical wireless communication (OWC) link operating in oceanic turbulence
      is formulated. BER variations against the changes in the ratio of temperature to
      salinity contributions to the refractive index spectrum, the rate of dissipation
      of mean-squared temperature, and the rate of dissipation of kinetic energy per
      unit mass of fluid are found at various data bit rates, average current gains of
      the avalanche photodiode (APD), and M values of the M-ary PPM. It is found that
      under any oceanic turbulence parameters, BER performance of the PPM OWC system
      becomes favorable at smaller data bit rates, M values, and at larger average
      current gains of APD.

PMID- 30182999
TI  - Solving analytically the simplified spherical harmonics equations in cylindrical
      turbid media.
AB  - A methodology is presented for analytically solving simplified spherical
      harmonics equations (SPN) in a finite homogeneous absorbing and scattering
      cylindrical medium. The SPN equations are a reliable approximation to the
      radiative transfer equation for describing light propagation inside turbid media.
      The equations consist of a set of coupled partial differential equations (PDEs).
      The analytical solution developed here is for a steady-state isotropic point
      source located at an arbitrary point inside a cylindrical turbid medium. Partial
      reflection boundary conditions are considered, as they realistically model the
      refractive index mismatch between a turbid medium and its surroundings (air), as
      occurs in practice in biomedical optics. The eigen method is used to decouple the
      set of SPN PDEs. The methodology is applied to the SP3, which has proved to be
      sufficiently accurate in practice, but it is readily generalizable to higher
      orders. The solution is compared with the analytical solution of the diffusion
      equation as well as to gold standard Monte Carlo simulations for validation,
      against which it shows good agreement. This work is important, as it provides an
      additional tool for validating numerical solutions of SPN equations for curved
      geometries, namely, cylindrical shapes, which are often used in practice.

PMID- 30183000
TI  - Three-dimensional localized chirped Airy-circular wave packets in free space.
AB  - By solving the (3+1)-dimensional free-space Schrodinger equation in circular
      cylindrical coordinates, we have systematically analyzed the propagation of
      chirped Airy-circular (CAiCi) wave packets. The complex amplitude of the CAiCi
      wave packets is constructed by the Airy function, the Gaussian function, and the
      confluent hypergeometric function. We find that the CAiCi wave packets are some
      coaxial ring pulses stacked along the temporal domain in the initial position,
      which are modulated by the chirped factor, the initial velocity, the distribution
      factor, and the propagation distance. Meanwhile, the wave packets will appear to
      undergo intensity attenuation, diffusion, convergence, and so on. We can also
      modulate the shape of the wave packets and change their optical properties by
      altering the mode numbers. Furthermore, we analyze the evolution properties of
      the wave packets in detail from the aspects of the gradient force, the scattering
      force, phase, the Poynting vector, and the angular momentum, and find some
      interesting phenomena.

PMID- 30183001
TI  - Disparity-selective stereo matching using correlation confidence measure.
AB  - Recently, the cost-volume filtering (CVF) methods for local stereo matching have
      provided fast and accurate results compared to those of the other method.
      However, CVF still causes incorrect results in the occlusion and texture-free
      regions. In particular, cost aggregation by pixel units involves complex
      computation because of its dependence on the image resolution and search range.
      This paper presents a robust stereo matching method for occluded regions. First,
      we generate cost volumes using the CENSUS transform and the scale-invariant
      feature transform (SIFT). Then, label-based cost volumes are aggregated using
      adaptive support weight and the simple linear iterative clustering (SLIC) scheme
      from two generated cost volumes. In order to obtain optimal disparity by two
      label-based cost volumes, we select the disparity corresponding to high
      confidence similarity of CENSUS or SIFT with minimum cost point. Experimental
      results show that our method estimates the optimal disparity in occlusion
      information, which exists only in the scene of one of the stereo pairs.

PMID- 30183002
TI  - Near-infrared polarimetric imaging and changes associated with normative aging.
AB  - With aging, the human retina undergoes cell death and additional structural
      changes that can increase scattered light. We quantified the effect of normative
      aging on multiply scattered light returning from the human fundus. As expected,
      there was an increase of multiply scattered light associated with aging, and this
      is consistent with the histological changes that occur in the fundus of
      individuals before developing age-related macular degeneration. This increase in
      scattered light with aging cannot be attributed to retinal reflectivity, anterior
      segment scatter, or pupil diameter.

PMID- 30183003
TI  - Theoretical investigations of infrared optical wave modulation transfer function
      models in anisotropic marine turbulence.
AB  - The previously derived marine turbulence modulation transfer function (MTF)
      adopts the classical assumption of isotropic and Kolmogorov turbulence. However,
      more theoretical research shows that marine turbulence demonstrates anisotropic
      non-Kolmogorov properties. In this study, new long-exposure plane and spherical
      wave MTF models under anisotropic non-Kolmogorov marine turbulence will be
      investigated. Comparative analyses are performed for the new models and the
      existing ones that have been developed under the isotropic marine turbulence and
      the anisotropic terrestrial turbulence cases. It turns out that the anisotropic
      marine turbulence influences the electro-optical imaging system less than the
      isotropic marine turbulence does. Also, under the same turbulence strength
      condition, due to the humidity fluctuations of marine atmosphere, the anisotropic
      marine turbulence will reduce more severely the quality of electro-optical
      imaging systems than the anisotropic terrestrial turbulence. Investigations
      conducted in this paper are beneficial to understand better the electro-optical
      imaging mechanism in marine atmospheric turbulence media.

PMID- 30183004
TI  - Scattering of a Laguerre-Gaussian beam by complicated shaped biological cells.
AB  - In this paper, we generalize the method of moments (MOM) based on the surface
      integral equation (SIE) method to investigate the scattering properties of
      complicated shaped biological cells illuminated by a Laguerre-Gaussian beam
      (LGB). We introduce the Lorentz-gauge vector potential with slowly varying
      envelope amplitude which satisfies the paraxial wave equation to obtain the
      electric and magnetic field components of the incident beam. The SIE method is
      applied to compute the scattering field of arbitrary shaped biological cells, the
      MLFMA is utilized to efficiently solve the resulting matrix equations, and a home
      made FORTRAN program is written. Then we explore the influence of the beam
      parameters (radial parameter, azimuthal parameter, waist radius, and beam center
      position of a LGB) on the differential scattering cross section (DSCS) for a red
      blood cell at great length. Some numerical results on the DSCS for complicated
      shaped biological cells, such as a fusiform cell and a bacteriophage anatomy
      illuminated by a LGB are given, showing the powerful capability of our approach.
      As a rapidly advancing field, the investigation of the scattering properties on
      complicated shaped biological cells illuminated by a LGB will hold a wealth of
      potential for the study of fundamental properties of light and exciting
      applications in the medical field.

PMID- 30183005
TI  - Degree of polarization in the focal region of a lens.
AB  - We examine the 3D distribution of the degree of polarization (DOP) in the focal
      region of a thin paraxial lens. Analytic expressions for the case of a focused
      Gaussian-Schell model beam are derived. These show that the DOP satisfies certain
      spatial symmetry relations. Furthermore, its value varies strongly in the
      vicinity of the geometrical focus, and its maximum, which need not occur at the
      focus, can be significantly higher than that of the incident beam.

PMID- 30183006
TI  - Reflection and refraction problems for metasurfaces related to Monge-Ampere
      equations.
AB  - A metasurface is a surface, typically a plane, on which a function called phase
      discontinuity is chosen so that the metasurface produces a desired reflection or
      refraction job. We derive the equations that the phase discontinuity function
      must satisfy, i.e., Monge-Ampere partial differential equations, and we prove the
      existence of solutions.

PMID- 30183007
TI  - Generalized parabolic nondiffracting beams of two orders.
AB  - In this paper we consider a generalization of standard nondiffracting parabolic
      beams. The proposed generalized beams have two orders: a continuous parameter a,
      as in standard beams, and the new parameter is an integer index m. Physically,
      the last parameter is equal to the number of rotated repetitions of the structure
      of the original angular spectrum on the total circle in the frequency space.
      Theoretical investigation shows that for a=0 the beams are real functions and
      have a symmetry of order 2m. If a?0 the beams will be real functions only for odd
      values of m. Moreover, in this case the beams have a symmetry of order m, while
      for even values of m the order of symmetry is 2m. The results of numerical
      simulation confirm these conclusions. Examples of generalized traveling parabolic
      waves, which are formed on the basis of generalized static parabolic beams, are
      also given.

PMID- 30183008
TI  - Spatio-spectral binary patterns based on multispectral filter arrays for texture
      classification.
AB  - To discriminate gray-level texture images, spatial texture descriptors can be
      extracted using the local binary pattern (LBP) operator. This operator has been
      extended to color images at the expense of increased memory and computation
      requirements. Some authors propose to compute texture descriptors directly from
      raw images provided through a Bayer color filter array, which both avoids the
      demosaicking step and reduces the descriptor size. Recently, multispectral
      snapshot cameras have emerged to sample more than three wavelength bands using a
      multispectral filter array. Such cameras provide a raw image in which a single
      spectral channel value is available at each pixel. In this paper we design a
      local binary pattern operator that jointly extracts the spatial and spectral
      texture information directly from a raw image. Extensive experiments on a large
      dataset show that the proposed descriptor has both reduced computation cost and
      high discriminative power with regard to classical LBP descriptors applied to
      demosaicked images.

PMID- 30183009
TI  - Direct detection receiver for vortex beam.
AB  - We present the theory of a direct detection receiver for vortex beams for an
      optical wireless communication system. The proposed receiver has an array of
      annular detectors, which enables analysis of power distribution of the vortex
      beam. We give a detailed description, numerical optimization, and different
      options for its design. One possible application of this receiver could be high
      security communication systems, and another could be intra data center
      communication. Using a given set of parameters, we find that a seven-ring
      symmetrically spaced detector is comparable to a three-ring detector with an
      optimized ring area.

PMID- 30183010
TI  - Plane-wave scattering by an ellipsoid composed of an orthorhombic dielectric
      magnetic material.
AB  - The extended boundary condition method can be used to study plane-wave scattering
      by an ellipsoid composed of an orthorhombic dielectric-magnetic material whose
      relative permittivity dyadic is a scalar multiple of its relative permeability
      dyadic. The scattered and internal field phasors can be expanded in terms of
      appropriate vector spherical wavefunctions with unknown expansion coefficients,
      whereas the incident-field phasors can be similarly expanded but with known
      expansion coefficients. The scattered-field coefficients are related to the
      incident-field coefficients through a matrix. The scattering, absorption, and
      extinction efficiencies were calculated thereby in relation to the propagation
      direction and the polarization state of the incident plane wave, the constitutive
      anisotropy parameters, and the nonsphericity parameters of the ellipsoid, when
      the eigenvectors of the real permittivity dyadic are aligned along the three semi
      axes of the ellipsoid. As the electrical size of the ellipsoid increases,
      multiple lobes appear in the scattering pattern. The total scattering efficiency
      can be smaller than the absorption efficiency for some configurations of the
      incident plane wave but not necessarily for others. The nonsphericity of the
      object has a stronger influence on the total scattering efficiency than on the
      absorption efficiency. The forward-scattering efficiency increases monotonically
      with the electrical size for all configurations of the incident plane wave, and
      so does the backscattering efficiency for some configurations. For other
      configurations, the backscattering efficiency has an undulating behavior with
      increase in electrical size and is highly affected by the shape and the
      constitutive anisotropy of the ellipsoid. Even though the ellipsoid is not
      necessarily a body of revolution, it is anisotropic, and it is not impedance
      matched to free space, the backscattering efficiency can be minuscule but the
      forward-scattering efficiency is not. This feature can be useful for harvesting
      electromagnetic energy.

PMID- 30183011
TI  - M-pulse amplitude modulation of a flat-topped beam for aeronautical laser
      communications.
AB  - Using the Rytov method, bit error rate (BER) performances of M-pulse amplitude
      modulation (M-PAM) are investigated for a flat-topped beam when such a beam is
      employed in an aeronautical laser communication system operating in vertical
      paths having weak atmospheric turbulence. By using the on-axis scintillation
      index and the log-normal distributed intensity, the average BER (?BER?) is
      evaluated for M-PAM when M=2,4,8. The scintillation indices of collimated flat
      topped beams of various flatness orders N are compared against propagation
      lengths, source sizes, and zenith angle for laser communication vertical paths,
      including uplink and downlink. Also, the ?BER? versus the average signal to noise
      ratio (?SNR?) is examined for various beam flatness orders. It is shown that as
      the flatness order increases, the scintillation index decreases. Taking one of
      the best flatness order values, N=15, for reducing the scintillations, ?BER?
      versus propagation lengths, source sizes, zenith angle, and ?SNR? are found for
      various values of M. When M is increased, the ?BER? is found to deteriorate.

PMID- 30183012
TI  - Hybrid camera array based calibration for computer-generated integral photography
      display.
AB  - Integral photography (IP) is one of the most promising 3D displays that can
      achieve a full parallax 3D display without glasses. There is a great need to
      render a correct, high-precision 3D image from an IP display. To achieve a
      correct 3D display, calibration is needed to correct optical misalignment and
      optical aberrations, while it is challenging to achieve correct mapping between a
      microlens array and matrix display. We propose an IP calibration method for a 3D
      autostereoscopic integral photography display based on a sparse camera array. Our
      method distinguishes itself from previous methods by estimating parameters for a
      dense correspondence map of an IP display with a relatively flexible setup and
      high precision in a reasonable time cost. We also propose a workflow to enable
      our method to handle both a visible and invisible microlens array and obtain a
      great outcome. One prototype is fabricated to evaluate the feasibility of the
      proposed method. Moreover, we evaluate our proposed method in geometry accuracy
      and image quality.

PMID- 30183013
TI  - Optical image processing with metasurface dark modes.
AB  - Here we consider image processing using the optical modes of metasurfaces with an
      angle-dependent excitation. These spatially dispersive modes can be used to
      directly manipulate the spatial frequency content of an incident field,
      suggesting their use as ultra-compact alternatives for analog optical information
      processing. A general framework for describing the filtering process in terms of
      the optical transfer functions is provided. In the case where the relevant mode
      cannot be excited with a normally incident plane wave (a dark mode), high-pass
      filtering is obtained. We provide examples demonstrating filtering of both
      amplitude and pure phase objects.

PMID- 30183014
TI  - Focal shift in tightly focused hybridly polarized Laguerre-Gaussian vector beams
      with zero radial index.
AB  - Hybridly polarized Laguerre-Gaussian vector beams (HPLGVBs) with zero radial
      index are obtained based on the third type of Laguerre-Gaussian vector beams.
      Polarization distributions of HPLGVBs are controlled by the phase retardation of
      a wave plate. The ellipticity angle and polarization orientation angle are used
      to describe the polarization distributions of the HPLGVBs. The electric field
      intensity distributions of tightly focused HPLGVBs are analyzed in the focal
      plane by the Richards-Wolf vectorial diffraction method. It is found that the
      tightly focused HPLGVBs have a focal shift phenomenon. The dependence of the
      focal shift of the HPLGVBs on the different parameters is discussed in detail.
      The simulation results show that the magnitude of the focal shift is related to
      the polarization distribution, and the focal shift is quite obvious for large
      azimuthal mode index, long focal length, large numerical aperture, and narrow
      beam waist. The effective control of the focal shift will have great potential
      applications in optical micromanipulation.

PMID- 30183015
TI  - Optimized angular selective filtering of direct solar radiation.
AB  - A method to optimize the angular selective filtering of direct solar radiation by
      minimization of light transmission of a window at a preset date and time of day,
      taking into account the orientation of the window to the cardinal, the latitude
      of the building, and the seasonal and daily distribution of solar radiation
      intensity, is described. Optimization is carried out using an optical filter with
      two thin-film surface gratings with alternating transmissive and non-transmissive
      parallel strips. The optimal slope angle of the strips to horizontal, the widths
      of the strips, the shift of input and output gratings relative to each other, and
      the angular characteristics of light transmittance are calculated.

PMID- 30183016
TI  - Formation of high-quality vortex laser beams with different orbital angular
      momenta in the laser resonator.
AB  - A scheme for forming high-quality vortex laser beams by employing spiral phase
      elements inside a laser resonator is presented theoretically. The calculated
      results show that the purity of the generated mode will decrease slightly as the
      mode order increases. However, the purity can achieve higher than 0.97 even for
      the high-order mode. More important, the value of the orbital angular momentum is
      controllable. Then, the influence of production and alignment errors, including
      the number of phase levels of the spiral phase elements, the surface roughness of
      the reflective mirrors, and the decenter of the reflective mirrors, is discussed
      in detail. The results show that the diffraction loss of the proposed system is
      more sensitive to production errors, and the purity of the generated mode is more
      sensitive to alignment errors. Thus, we estimate that the height of one step of
      the spiral structure should be less than one-fifteenth of the wavelength, the
      maximum surface fluctuation should be less than one-twentieth of the wavelength,
      and the vertical distance between the centers of the two reflective mirrors
      should be less than 20 MUm if one wants to obtain high-quality vortex laser beams
      with high efficiency. The requirements for precision are acceptable for existing
      microfabrication and operation technologies.

PMID- 30183017
TI  - Transmission of a polychromatic electromagnetic multi-Gaussian Schell-model beam
      in an inhomogeneous gradient-index fiber.
AB  - We derive analytical expressions for the cross-spectral density matrix of
      polychromatic electromagnetic multi-Gaussian Schell-model (EMGSM) beam
      transmission through a gradient-index fiber. The space-spectrum evolution
      properties for the spectral density, spectral shift, degree of polarization, and
      electromagnetic coherence state of a polychromatic EMGSM beam with Lorentzian
      line type spectrum and central wavelength lambda0=1550  nm propagation in a
      silica-clad germania core inhomogeneous graded-index fiber are studied in detail.
      We show that these statistical properties exhibit periodicity in the fiber,
      caused by the focusing property of square-law media, which can be reminiscent of
      the self-imaging effect of optical fields. The effects of the nonconventional
      correlation functions of the polychromatic EMGSM beam on the transmission
      properties are also investigated.

PMID- 30183018
TI  - Direct comparison between subnanometer hydration structures on hydrophilic and
      hydrophobic surfaces via three-dimensional scanning force microscopy.
AB  - Investigating interfacial water ordering on solid surfaces with different
      hydrophobicities is fundamentally important. Here, we prepared hydrophilic mica
      substrates with some areas covered by mildly hydrophobic graphene layers and
      studied the resulting hydration layers using three-dimensional (3D) force
      measurements based on frequency-modulation atomic force microscopy. Hydration
      layers of 0.3-0.6 nm were detected on bare graphene regions; these layers were
      considerably larger than the spacing measured on mica (0.2-0.3 nm). On the
      graphene-covered regions, we also observed the formation of special ordered
      structures of adsorbates over time, on which, surprisingly, no prominent
      hydration layers were detected. Based on these findings, we present one possible
      scenario to describe the formation process of the ordered interfacial structures
      and the enhanced oscillation period in the force profiles. This work also
      demonstrates the capability and significance of 3D force measurements in probing
      hydration behaviors on a heterogeneous substrate with a lateral resolution
      smaller than several nanometers.

PMID- 30183019
TI  - Role of cerium oxide in bioactive glasses during catalytic dissociation of
      hydrogen peroxide.
AB  - The addition of cerium oxide to bioactive glasses, important materials for bone
      tissue regeneration, has been shown to induce multifunctionality, combining a
      significant bioactivity with antioxidant properties. We provide a real time
      investigation of the evolution of the electronic properties of highly diluted
      cerium ions in a liquid environment containing hydrogen peroxide - the most
      abundant reactive oxygen species in living cells. This challenging task is
      undertaken by means of high-energy resolution fluorescence detected by X-ray
      absorption near-edge spectroscopy at the Ce L3 edge. We investigate samples with
      variable compositions and different morphologies. We relate the observed
      spectroscopic changes not only to variations in the concentration of the two Ce
      oxidation states in the samples, but also to changes in the local atomic
      environment of Ce ions, providing a clear picture of the role of cerium ions in
      the dissociation of hydrogen peroxide. The obtained results contribute to the
      understanding of the mechanisms that come into play in the process and provide a
      basis for the optimization of the functionalities of this class of materials.

PMID- 30183020
TI  - Bismuth(iii)-thiophenedicarboxylates as host frameworks for lanthanide ions:
      synthesis, structural characterization, and photoluminescent behavior.
AB  - Three bismuth-2,5-thiophenedicarboxylates (Bi-TDC) and two europium-2,5
      thiophenedicarboxylates (Eu-TDC) were synthesized under ambient conditions. The
      structures were determined through single crystal X-ray diffraction, and three of
      the phases were further characterized by powder X-ray diffraction, Raman
      spectroscopy, and thermogravimetric analysis. Reactions of bismuth nitrate, 2,5
      thiophenedicarboxylate, and pyridine in an acidic solution of acetic acid and
      ethanol yield Hpy[Bi(TDC)2(H2O)].1.5H2O (1), whereas reactions in a water/ethanol
      mixture produce a minor phase, [Hpy]3[Bi2(TDC)4(HTDC)(H2O)].xH2O (2) along with a
      major product, (Hpy)2[Bi(TDC)2(HTDC)].0.36H2O (3). The structures of 1-3 are all
      built from anionic Bi-TDC chains that are further bridged through additional TDC
      linkages into interpenetrated 2D sheets. Addition of an aqueous lanthanide
      solution to the reaction mixtures that yielded 1 and 2-3 resulted in the
      formation of doped phases, Hpy[Bi1-xLnx(TDC)2(H2O)].1.5H2O (Bi1-xLnx-1), where Ln
      = Nd, Sm, Eu, Tb, Dy, and Yb, and (Hpy)2[Bi0.99Eu0.01 (TDC)2(HTDC)].0.36H2O
      (Bi0.99Eu0.01-3). Using europium nitrate rather than the bismuth precursor
      resulted in the formation of two homometallic europium based phases,
      [Eu(TDC)(NO3)(H2O)]n (4) and [Eu2(TDC)3(H2O)9].5H2O (5), which adopt an extended
      3D network and an interpenetrated 2D structure, respectively. Photophysical
      measurements were carried out for 1 and the lanthanide containing phases and
      quantum yield and lifetime values were determined for the visible light emitters.
      Herein, the structural chemistry, spectroscopic properties, and luminescence of
      the bismuth phases, their lanthanide doped analogs, and the europium compounds
      are presented.

PMID- 30183021
TI  - The first investigation of europium silicate melilite for second-order nonlinear
      optical application: experimental and theoretical studies.
AB  - A europium pyrosilicate, Eu2MgSi2O7 (1), is obtained using a high-temperature
      solid-state reaction. It crystallizes in the tetragonal noncentrosymmetric space
      group P4[combining macron]21m, and its structure features a 2D structure built by
      SiO4 and MgO4 tetrahedra, resulting in interlayer cavities occupied by Eu2+ ions.
      It has a SHG intensity around 0.7 times that of KTP in the particle size range of
      45-75 MUm under 2.1 MUm radiation, demonstrating a relatively strong effect among
      the silicates. A typical photoluminescence phenomenon of Eu2+ can be observed at
      482 nm. Calculations on the electronic structure and optical properties of 1 are
      performed. Moreover, to discuss the potential of pyrosilicates and related
      compounds as NLO crystals, the theoretical analysis on other A2BM2O7 compounds is
      also addressed.

PMID- 30183022
TI  - Spindle nodal chain in three-dimensional alpha' boron.
AB  - Topological metals/semimetals (TMs) have emerged as a new frontier in the field
      of quantum materials. A few two-dimensional (2D) boron sheets have been suggested
      as Dirac materials, however, to date TMs made of three-dimensional (3D) boron
      structures have not been found. Herein, by means of systematic first principles
      computations, we discovered that a rather stable 3D boron allotrope, namely 3D
      alpha' boron, is a nodal-chain semimetal. In momentum space, six nodal lines and
      rings contact each other and form a novel spindle nodal chain. This 3D-alpha'
      boron can be formed by stacking 2D wiggle alpha' boron sheets, which are also
      nodal-ring semimetals. In addition, our chemical bond analysis revealed that the
      topological properties of the 3D and 2D boron structures are related to the pi
      bonds between boron atoms, however, the bonding characteristics are different
      from those in the 2D and 3D carbon structures.

PMID- 30183023
TI  - Synergistic interplay of Zn and Rh-Cr promoters on Ga2O3 based photocatalysts for
      water splitting.
AB  - The photocatalytic water splitting activity of a wide-bandgap material, Ga2O3, is
      greatly boosted with the addition of a Zn and Rh-Cr co-catalyst at optimum
      loadings. To date, however, the exact roles of the co-catalysts and particularly
      the origin of their synergistic functions have not been clarified. Herein, we
      present how the optimum Zn loading on Ga2O3 leads to creation of a ZnGa2O4/Ga2O3
      heterojunction favorable for charge separation through information on the
      occupied and unoccupied electronic states of Zn and Ga elucidated by X-ray
      absorption and emission spectroscopic methods. The function of Rh-Cr as an
      electron sink and reduction site was proven by photocatalytic experiments using
      an electron scavenger (Ag+) and by learning where Ag deposits and its effects on
      photocatalytic activity. Finally, perturbation of the Zn electronic structure by
      photoactivation was evidenced by modulation excitation X-ray absorption
      spectroscopy. Importantly, Rh-Cr markedly enhanced the level of the perturbation,
      serving as proof of the direct communication and synergy between the electronic
      states of Zn, present in ZnGa2O4, and Rh-Cr deposited on Ga2O3.

PMID- 30183024
TI  - Distinct spin-lattice and spin-phonon interactions in monolayer magnetic CrI3.
AB  - We apply the density-functional theory to study various phases (including non
      magnetic (NM), anti-ferromagnetic (AFM), and ferromagnetic (FM)) in monolayer
      magnetic chromium triiodide (CrI3), a recently fabricated 2D magnetic material.
      It is found that: (1) the introduction of magnetism in monolayer CrI3 gives rise
      to metal-to-semiconductor transition; (2) the electronic band topologies as well
      as the nature of direct and indirect band gaps in either AFM or FM phases exhibit
      delicate dependence on the magnetic ordering and spin-orbit coupling; and (3) the
      phonon modes involving Cr atoms are particularly sensitive to the magnetic
      ordering, highlighting distinct spin-lattice and spin-phonon coupling in this
      magnet. First-principles simulations of the Raman spectra demonstrate that both
      frequencies and intensities of the Raman peaks strongly depend on the magnetic
      ordering. The polarization dependent A1g modes at 77 cm-1 and 130 cm-1 along with
      the Eg mode at about 50 cm-1 in the FM phase may offer a useful fingerprint to
      characterize this material. Our results not only provide a detailed guiding map
      for experimental characterization of CrI3, but also reveal how the evolution of
      magnetism can be tracked by its lattice dynamics and Raman response.

PMID- 30183025
TI  - Group 15 biradicals: synthesis and reactivity of cyclobutane-1,3-diyl and
      cyclopentane-1,3-diyl analogues.
AB  - Readily accessible group 15 biradicals of the type [E(MU-NR)]2 (E = P-Bi) form
      planar 6pi-electronic-4-membered heterocycles featuring open-shell singlet
      biradical character. They can be utilized to activate small molecules bearing
      single, double and triple bonds as well as to trap labile in situ generated
      fragments. In the reaction with CO and R-NC (R = small alkyl or aryl substituent)
      pnictogen analogues of cyclopentane-1,3-diyl are formed which represent robust
      molecular switches. Group 15 biradicals with two different radical sites display
      regioselectivity upon addition of small molecules.

PMID- 30183026
TI  - Naphthalene containing amino-ether macrocycle based Cu(ii) templated
      [2]pseudorotaxanes and OFF/ON fluorescence switching via axle substitution.
AB  - A new naphthalene containing macrocycle, NaphMC, and a new fluorophoric bidentate
      linear axle derivative of 5,5'-dimethyl-2,2'-bipyridine (L3) along with two other
      ligands 1,10-phenanthroline (L1) and 5,5'-dimethyl-2,2'-bipyridine (L2) are
      explored towards the synthesis of Cu(ii) templated [2]pseudorotaxanes. All
      ternary complexes are well characterized by ESI-MS, UV/Vis, EPR spectroscopy,
      elemental analysis and emission spectroscopic studies. Single crystal X-ray
      diffraction studies confirm the geometry around the Cu(ii) center as a distorted
      trigonal bipyramid via the contribution of [3 + 2] orthogonal motifs of the wheel
      (NaphMC) and the bidentate chelating ligands L1 and L2 in the cases of
      pseudorotaxanes, CuPR1 and CuPR2, respectively. Furthermore, the fluorescence
      "OFF" state of the fluorophoric axle L3 is achieved via threading it to the
      Cu(ii) complex of NaphMC, whereas fluorescence switching "ON" is demonstrated by
      the substitution of L3 of CuPR3 with a stronger chelating ligand L1.

PMID- 30183027
TI  - Lithium insertion into silicon electrodes studied by cyclic voltammetry and
      operando neutron reflectometry.
AB  - Operando neutron reflectometry measurements were carried out to study the
      insertion of lithium into amorphous silicon film electrodes during cyclic
      voltammetry (CV) experiments at a scan rate of 0.01 mV s-1. The experiments allow
      mapping of regions where significant amounts of Li are incorporated/released from
      the electrode and correlation of the results to modifications of characteristic
      peaks in the CV curve. High volume changes up to 390% accompanied by
      corresponding modifications of the neutron scattering length density (which is a
      measure of the average Li fraction present in the electrode) are observed during
      electrochemical cycling for potentials below 0.3 V (lithiation) and above 0.2 V
      (delithiation), leading to a hysteretic behaviour. This is attributed to result
      from mechanical stress as suggested in the literature. Formation and modification
      of a surface layer associated with the solid electrolyte interphase (SEI) were
      observed during cycling. Within the first lithiation cycle the SEI grows to 120 A
      for potentials below 0.5 V. Afterwards a reversible and stable modification of
      the SEI between 70 A (delithiated state) and 120 A (lithiated state) takes place.

PMID- 30183028
TI  - Small neutral Gd(iii) tags for distance measurements in proteins by double
      electron-electron resonance experiments.
AB  - Spin labels containing a Gd(iii) ion have become important for measuring
      nanometer distances in proteins by double electron-electron resonance (DEER)
      experiments at high EPR frequencies. The distance resolution and sensitivity of
      these measurements strongly depend on the Gd(iii) tag used. Here we report the
      performance of two Gd(iii) tags, propargyl-DO3A and C11 in DEER experiments
      carried out at W-band (95 GHz). Both tags are small, uncharged and devoid of
      bulky hydrophobic pendants. The propargyl-DO3A tag is designed for conjugation to
      the azide-group of an unnatural amino acid. The C11 tag is a new tag designed for
      attachment to a single cysteine residue. The tags delivered narrower distance
      distributions in the E. coli aspartate/glutamate binding protein and the Zika
      virus NS2B-NS3 protease than previously established Gd(iii) tags. The improved
      performance is consistent with the absence of specific hydrophobic or charge
      charge interactions with the protein. In the case of the Zika virus NS2B-NS3
      protease, unexpectedly broad Gd(iii)-Gd(iii) distance distributions observed with
      the previously published charged C9 tag, but not the C11 tag, illustrate the
      potential of tags to perturb a labile protein structure and the importance of
      different tags. The results obtained with the C11 tag demonstrate the closed
      conformation in the commonly used linked construct of the Zika virus NS2B-NS3
      protease, both in the presence and absence of an inhibitor.

PMID- 30183029
TI  - Near-infrared broadband cavity-enhanced sensor system for methane detection using
      a wavelet-denoising assisted Fourier-transform spectrometer.
AB  - The majority of broadband cavity-enhanced systems are used to detect trace gas
      species in the visible spectral range. We demonstrated a broadband cavity
      enhanced sensor system in combination with a Fourier-transform spectrometer (FTS)
      in the near-infrared (near-IR) region for methane (CH4) detection. Light from a
      tungsten-halogen lamp was coupled into a high-finesse cavity and the light
      leaking from the cavity was imaged onto the FTS. An optimal incident beam
      diameter of 2.25 cm was required in the condition of a 40 cm-long cavity of a 2.5
      cm diameter and a 100 cm radius of curvature (RoC) mirror. The CH4 sensor system
      was capable of operating at a temperature of 300 K and 1 atm gas pressure. Based
      on an Allan variance analysis, a minimum detectable absorption coefficient of 4.6
      * 10-7 cm-1 was achieved. A wavelet denoising (WD) method was introduced in the
      retrieval of the gas concentration, which improved the measurement precision from
      10.2 parts-per-million in volume (ppmv) to 5.3 ppmv with an enhancement factor of
      2 for a 20 min averaging time. The near-IR broadband cavity-enhanced sensor
      system can also be used to measure high-resolution absorption spectra of other
      atmospheric trace gas species.

PMID- 30183030
TI  - Blood-based near-infrared spectroscopy for the rapid low-cost detection of
      Alzheimer's disease.
AB  - Alzheimer's disease (AD) is currently under-diagnosed and is predicted to affect
      a great number of people in the future, due to the unrestrained aging of the
      population. An accurate diagnosis of AD at an early stage, prior to (severe)
      symptomatology, is of crucial importance as it would allow the subscription of
      effective palliative care and/or enrolment into specific clinical trials. Today,
      new analytical methods and research initiatives are being developed for the on
      time diagnosis of this devastating disorder. During the last decade,
      spectroscopic techniques have shown great promise in the robust diagnosis of
      various pathologies, including neurodegenerative diseases and dementia. In the
      current study, blood plasma samples were analysed with near-infrared (NIR)
      spectroscopy as a minimally-invasive method to distinguish patients with AD (n =
      111) from non-demented volunteers (n = 173). After applying multivariate
      classification models (principal component analysis with quadratic discriminant
      analysis - PCA-QDA), AD individuals were correctly identified with 92.8%
      accuracy, 87.5% sensitivity and 96.1% specificity. Our results show the potential
      of NIR spectroscopy as a simple and cost-effective diagnostic tool for AD. Robust
      and early diagnosis may be a first step towards tackling this disease by allowing
      timely intervention.

PMID- 30183031
TI  - Effects and controls of capacitive hysteresis in ionic liquid electrochemical
      measurements.
AB  - Capacitance vs. potential relationships help electrochemists better understand
      electrode-liquid interfacial behaviors. However, the current ionic liquid
      literature does not have a unified experimental approach, and hysteresis effects
      are of significant concern. Known experimental variables that can influence
      capacitance-potential data include electrode material and morphology, potential
      scan direction, equivalent circuit model applied during analysis, and, to some
      extent, the electrochemical technique employed. To our knowledge, the present
      work is the first systematic study of four major variables that are relevant to
      IL-based capacitance measurements, and of their effects on resulting capacitance
      curvature. We examine: (1) the potential range explored, (2) the potential scan
      direction applied, (3) the data acquisition protocol used to collect data, and
      (4) the electrochemical technique used to generate capacitance data.
      Specifically, we find that all four of these (some more than others) 'user
      defined' experimental variables influence the resulting capacitance-potential
      curvature for a typical ionic liquid electrochemical system. In an effort to
      minimize bias and to permit better comparisons of data collected from different
      laboratories we provide guidelines to help critically assess IL capacitance
      potential data.

PMID- 30183032
TI  - Pushing the frontiers: boron-11 NMR as a method for quantitative boron analysis
      and its application to determine boric acid in commercial biocides.
AB  - Quantitative boron-11 NMR (11B qNMR) spectroscopy has been introduced for the
      first time as a method to determine boric acid content in commercial biocides.
      Validation of the method affords a limit of detection of 0.02% w/w and a limit of
      quantification of 0.04% w/w, which are low enough to determine boric acid in
      commercial biocides. Other figures of merit such as linearity (R2 > 0.99),
      recovery (93.6%-106.2%), intra- and inter-day precision (from 0.7 to 2.0%),
      uncertainty (3.7 to 4.4%) and matrix effects were also evaluated. This method was
      successfully applied to determine boric acid in five different commercial
      biocides in a wide range of concentrations (<0.05 to 10% w/w) providing excellent
      results when they were compared with those obtained using inductively coupled
      plasma-mass spectrometry (ICP-MS). The suitability of this method for a fast and
      reliable quantification of boric acid in commercial biocide preparations has been
      demonstrated. The absence of the matrix effect allows the application of this
      validated method for the determination of boric acid in other matrices of diverse
      composition.

PMID- 30183033
TI  - The oxygen reduction reaction on [NiFe] hydrogenases.
AB  - Oxygen tolerance capacity is critical for hydrogen oxidation/evolution catalysts.
      In nature, [NiFe] hydrogenases show excellent O2-tolerance and can rapidly
      reactivate the active site. This work aims to understand the reduction of O2 on
      the active site of [NiFe] hydrogenases. From the density functional theory (DFT)
      calculations, the free energy diagram for the oxygen reduction reaction (ORR) has
      been derived and the rate-determining step is found to be the Ni-B to Ni-SIb'
      step. Our calculation explains the slow reactivation for the Ni-A state compared
      to the Ni-B state, which is due to the particularly stable structure of the Ni-A
      state.

PMID- 30183034
TI  - A heterobimetallic single-source precursor enabled layered oxide cathode for
      sodium-ion batteries.
AB  - A single-source precursor NaCo(acac)3 (acac = acetylacetone) for layered oxide
      cathodes of sodium-ion batteries (SIBs) is reported here. It features a 1D chain
      structure, and is prepared in nearly quantitative yield employing commercially
      available reagents. The complex is stable in open air and tends to dissolve in
      various strongly polar solvents, including H2O and methanol. The phase-pure
      layered oxide cathode material P2-NaxCoO2 for SIBs is obtained through calcining
      the complex, and exhibits an excellent rate capability, even superior to the
      recently reported P2-NaxCoO2 microspheres. More analogue complexes could be
      obtained through cationic replacement for the synthesis of other high-performance
      layered metal oxides for SIBs.

PMID- 30183035
TI  - Two-electron redox-active tricyano iron(ii) complex with 2,4,6-tris(2-pyrimidyl)
      1,3,5-triazine as a building block for coordination polymers.
AB  - A new tricyano iron(ii) building unit, [{K(H2O)4}{FeII(CN)3(L)}].3H2O (1), was
      synthesized by the reaction of Moor's salts with 2,4,6-tris(2-pyrimidyl)-1,3,5
      triazine (L) as a capping ligand. X-ray structural analysis reveals that the
      mononuclear iron(ii) tricyano complex consists of one ligand and three cyanide
      groups, with K+ ions coordinated between neighboring units to form a one
      dimensional chain network structure. 1 shows two reversible redox waves at +0.713
      and -0.849 V vs. SCE, which are assigned as Fe(ii)/Fe(iii) and L/L- processes,
      respectively. One-dimensional 4,2-ribbon chain type coordination polymers,
      [MII(H2O)2{FeII(CN)3(L)}2].6H2O (M = Fe (2) and Mn (3)), were synthesized by
      using 1 as a building unit. Cryomagnetic studies reveals that 2 and 3 show
      paramagnetic behaviour of S = 2 and 5/2, respectively. On the other hand,
      reaction of 1 and Gd(NO3)3.6H2O forms another one-dimensional chain,
      [GdIII(NO3)2(H2O)3{FeII(CN)3(L)}].0.5H2O.2CH3OH (4), showing S = 7/2 paramagnetic
      behaviour.

PMID- 30183036
TI  - A sui generis electrode-driven spatial confinement effect responsible for strong
      twisting enhancement of floppy molecules in closely packed self-assembled
      monolayers.
AB  - At present, it is widely accepted that properties (e.g., molecular conformation)
      of molecules adsorbed to form self-assembled monolayers (SAMs) on electrodes can
      be very different from isolated species because of a substantial charge transfer
      or specific chemical bonding at the interface. Contrary to this view, the
      theoretical results presented here predict that the strong twisting angle (phi)
      enhancement of floppy molecules adsorbed to form densely packed SAMs on most
      common electrodes (Pt, Au, Ag, and Cu) is neither due to charge transfer nor to
      specific bonding but rather to a sui generis electrode-driven spatial confinement
      effect that can be quantitatively described within an electrode-free two
      dimensional model. We predict a logistic ("Fermi-Dirac") growth pattern of phi as
      the coverage approaches the value characteristic of a herringbone arrangement,
      which is twice the value for isolated molecules or low-coverage SAMs.

PMID- 30183037
TI  - Probiotics, mechanisms of action, and clinical perspectives for diarrhea
      management in children.
AB  - Infectious diarrhea is the second most common cause of morbidity and mortality in
      children under 5 years of age in the underdeveloped areas of the world.
      Conventional treatment consists of rehydration, which may be coupled with
      antimicrobial agents in more severe bacterial infections or with antiprotozoal
      agents. In the last few decades, research on the use of probiotic strains, such
      as Lactobacillus rhamnosus GG ATCC 53013 (LGG), Lactobacillus reuteri DSM 17938
      and Saccharomyces boulardii, has gained much attention to prevent and treat
      diarrheal diseases. However, they are rarely used in the clinical routine,
      perhaps because there are still gaps in the knowledge about the effective benefit
      to the patient in terms of the reduction of the duration of diarrhea and its
      prevention. Furthermore, only a few probiotic strains are safely indicated for
      usage in pediatric practice. This review summarizes the current knowledge on the
      antimicrobial mechanisms of probiotics on distinct enteropathogens and their role
      in stimulating host defense mechanisms against intestinal infections. In
      addition, we highlight the potential of probiotics for the treatment and
      prevention of diarrhea in children. We conclude that the use of probiotics is
      beneficial for both the treatment and prevention of diarrhea in children and that
      the identification of other candidate probiotics might represent an important
      advance to a greater reduction in hospital stays and to prevent infectious
      diarrhea in a larger portion of this population.

PMID- 30183038
TI  - Synthesis of novel copper-rare earth BINOLate frameworks from a hydrogen bonding
      DBU-H rare earth BINOLate complex.
AB  - The preparation of a novel H-bonding DBU-H+ BINOLate Rare Earth Metal complex
      enabled the synthesis of the first copper-Rare Earth Metal BINOLate complex
      (CuDBU-REMB). CuDBU-REMB was compared to the analogous Li complex using X-ray
      crystallography and Exchange NMR spectroscopy (EXSY). The results provide insight
      into the role of the secondary metal cation in the framework's stabilization.

PMID- 30183039
TI  - (-)-Epigallocatechin-3-gallate (EGCG) inhibits starch digestion and improves
      glucose homeostasis through direct or indirect activation of PXR/CAR-mediated
      phase II metabolism in diabetic mice.
AB  - As a major component of green tea, (-)-epigallocatechin-3-gallate (EGCG) has
      attracted interest from scientists owing to its potential to combat a variety of
      human diseases including abnormal glucose metabolism in obesity and diabetes.
      This study aims to (1) evaluate the molecular mechanism of EGCG in starch
      digestion before EGCG absorption; (2) investigate the link between PXR/CAR
      mediated phase II metabolism and glucose homeostasis after EGCG is transported to
      small intestine and liver. EGCG suppressed starch hydrolysis both in vitro and in
      vivo. Molecular simulation results demonstrated that EGCG could bind to the
      active site of alpha-amylase and alpha-glucosidase, acting as an inhibitor. In
      addition, the anti-diabetic action of EGCG was investigated in high fat diet and
      STZ-induced type 2 diabetes. EGCG improved glucose homeostasis and inhibited the
      process of gluconeogenesis (PEPCK and G-6-Pase) and lipogenesis (SREBP-1C, FAS
      and ACC1) in the liver. Meanwhile, EGCG treatment activated PXR/CAR, accompanied
      by upgrading PXR/CAR-mediated phase II drug metabolism enzyme expression in small
      intestine and liver, involving SULT1A1, UGT1A1 and SULT2B1b. Dietary polyphenol
      EGCG could serve as a promising PXR/CAR activator and therapeutic intervention in
      diabetes.

PMID- 30183040
TI  - A dimorphism shift of hepatitis B virus capsids in response to ionic conditions.
AB  - The dimorphism of HBV capsids (coexistence of T = 3 and T = 4 capsids) was found
      to be regulatable by controlling the rate of capsid nucleation using cations such
      as K+ or Ca2+: a quick addition of highly concentrated monovalent and/or
      multivalent counter-cations resulted in a morphism transition from a
      thermodynamically more stable, T = 4 capsid-dominant state (>80% of total
      capsids) to a new state containing ~1 : 1 amounts of T = 3 and T = 4 capsids.
      These results suggested that the salts with strong charge screening ability could
      narrow the difference in nucleation energy barriers between the two states, which
      were not inter-convertible once formed. The effect of salts was more significant
      than other factors such as pH or protein concentration in achieving such a
      dimorphism shift. The general mechanism of HBV capsid dimorphism described here
      provides a new perspective in understanding the virus assembly during infection
      and directing the design of non-infectious capsids for nanotechnology
      applications.

PMID- 30183041
TI  - Correction: Recent trends in the structural revision of natural products.
AB  - Correction for 'Recent trends in the structural revision of natural products' by
      Bhuwan Khatri Chhetri et al., Nat. Prod. Rep., 2018, 35, 514-531.

PMID- 30183043
TI  - Wetting of soft superhydrophobic micropillar arrays.
AB  - Superhydrophobic surfaces are usually assumed to be rigid so that liquids do not
      deform them. Here we analyze how the relation between microstructure and wetting
      changes when the surface is flexible. Therefore we deposited liquid drops on
      arrays of flexible micropillars. We imaged the drop's surface and the bending of
      micropillars with confocal microscopy and analyzed the deflection of micropillars
      while the contact line advanced and receded. The deflection is directly
      proportional to the horizontal component of the capillary force acting on that
      particular micropillar. In the Cassie or "fakir" state, drops advance by touching
      down on the next top faces of micropillars, much like on rigid arrays. In
      contrast, on the receding side the micropillars deform. The main force hindering
      the slide of a drop is due to pinning at the receding side, while the force on
      the advancing side is negligible. In the Wenzel state, micropillars were
      deflected in both receding and advancing states.

PMID- 30183044
TI  - High strength and ductility of graphene-like carbon nanosheet/copper composites
      fabricated directly from commercial oleic acid coated copper powders.
AB  - Recently, copper matrix composites reinforced with graphene or graphene-like
      carbon nanosheets (GNS) have attracted great attention due to their excellent
      properties. However, the fabrication technologies of the composites are generally
      complex and expensive; it is necessary to develop facile and cheap synthesis
      methods for industrial applications of the composites with high performance.
      Here, we present a very simple method to fabricate GNS reinforced copper
      composites: commercial Cu powders with oleic acid coating are directly fabricated
      into GNS/Cu composites by spark plasma sintering. This work provides a facile
      method with low cost and high efficiency for the preparation of GNS reinforced
      metal matrix composites with high performance, which opens a new window for the
      large-scale production of graphene based composites.

PMID- 30183042
TI  - MnIII-Peroxo adduct supported by a new tetradentate ligand shows acid-sensitive
      aldehyde deformylation reactivity.
AB  - The new tetradentate L7BQ ligand (L7BQ = 1,4-di(quinoline-8-yl)-1,4-diazepane)
      has been synthesized and shown to support MnII and MnIII-peroxo complexes. X-ray
      crystallography of the [MnII(L7BQ)(OTf)2] complex shows a monomeric MnII center
      with the L7BQ ligand providing four donor nitrogen atoms in the equatorial field,
      with two triflate ions bound in the axial positions. When this species is treated
      with H2O2 and Et3N at -40  degrees C, a MnIII-peroxo adduct, [MnIII(O2)(L7BQ)]+
      is formed. The formation of this new intermediate is supported by a variety of
      spectroscopic techniques, including electronic absorption, Mn K-edge X-ray
      absorption and electron paramagnetic resonance methods. Evaluation of extended X
      ray absorption fine structure data for [MnIII(O2)(L7BQ)]+ resolved Mn-O bond
      distances of 1.85 A, which are on the short end of those previously reported for
      crystallographically characterized MnIII-peroxo adducts. An analysis of the X-ray
      pre-edge region of [MnIII(O2)(L7BQ)]+ revealed a large pre-edge area of 20.8
      units. Time-dependent density functional theory computations indicate that the
      pre-edge intensity is due to Mn 4p-3d mixing caused by geometric distortions from
      centrosymmetry induced by both the peroxo and L7BQ ligands. The reactivity of
      [MnIII(O2)(L7BQ)]+ towards aldehydes was assessed through reaction with
      cyclohexanecarboxaldehyde and 2-phenylpropionaldehyde. From these experiments, it
      was determined that [MnIII(O2)(L7BQ)]+ only reacts with aldehydes in the presence
      of acid. Specifically, the addition of cyclohexanecarboxylic acid to
      [MnIII(O2)(L7BQ)]+ converts the MnIII-peroxo adduct to a new intermediate that
      could be responsible for the observed aldehyde deformylation activity. These
      observations underscore the challenges in identifying the reactive metal species
      in aldehyde deformylation reactions.

PMID- 30183045
TI  - Iron-decorated nitrogen-rich carbons as efficient oxygen reduction
      electrocatalysts for Zn-air batteries.
AB  - A low-cost and scalable method has been developed to synthesize Fe-decorated N
      rich carbon electrocatalysts for the oxygen reduction reaction (ORR) based on
      pyrolysis of metal carbonyls containing metal-organic frameworks (MOFs). Such a
      method simultaneously optimizes the Fe-related active sites and the porous
      structure of the catalysts. Accordingly, the best-performing Fe-NC-900-M catalyst
      shows excellent ORR activity with a half-wave potential of 0.91 V vs. RHE,
      exceeding that of the 40% Pt/C catalyst in alkaline media. Furthermore, the zinc
      air batteries constructed with Fe-NC-900-M as the cathode catalyst exhibit high
      open-circuit voltage (1.5 V) and peak power density (271 mW cm-2), and outperform
      most zinc-air batteries with noble-metal free ORR catalysts.

PMID- 30183046
TI  - Synthesis of self-assembled PtPdAg nanostructures with a high catalytic activity
      for oxygen reduction reactions.
AB  - Designing a self-assembling structure for a Pt-based catalyst offers a great
      opportunity to enhance the electrocatalytic performance and maximize the use of
      precious metals. Herein, we report an etching method based on thermal treatment
      for the removal of less active metals from Pt-based alloys for the enhancement of
      the oxygen reduction reaction. PtPdAg nanostructures' self-assembly can be easily
      controlled to the dimer stage or nanowires by stirring the nanoparticles in
      formamide with or without potassium iodide under heat for specific times. Thus
      oxygen reduction reaction-favoring PtPdAg hollow nanoparticle, nanodimer and
      nanowire catalysts are synthesized, all of which have been demonstrated to be
      promoting factors for the ORR. In a Pt-based catalyst, the arrangement and
      configuration of the surface or topmost few layer atoms influence the adsorption
      of oxygen and activation for ORR. The PtPdAg dimer catalyst shows excellent ORR
      activity compared to other PtPdAg nanostructures and commercial Pt/C i.e. 7.2
      times higher specific activity and 4.1 times higher mass activity. We further
      carried out DFT calculations and from the results, we conclude that the most
      chemically inequivalent structure such as PtPdAg/C nanodimer alloys possesses the
      weakest oxygen binding energy.

PMID- 30183047
TI  - Preparation of homoallylic amines via a three-component coupling process.
AB  - A three-component synthesis of homoallylic amines is described. The allylboronic
      species were generated in situ by homologation of vinyl boroxines with
      trimethylsilyldiazomethane, then followed by trapping of the allylboron
      intermediate with imines. Twenty-seven compounds were successfully prepared in
      moderate to high yields. Imines bearing various functional groups were tolerated,
      including aliphatic, aromatic and heteroaromatic substituents. Further
      elaboration of some of the homoallylic amines to form azeditines is also
      reported.

PMID- 30183048
TI  - Enantioselective syntheses and application of 4-epi-galiellalactone and the
      corresponding activity-based probe: from strained bicycles to strained tricycles.
AB  - The [6,5,5] tricyclic fungal metabolite galiellalactone is a Michael acceptor
      that has been demonstrated to be a covalent inhibitor for Signal Transducer and
      Activator of Transcription 3 (STAT3). Recognizing the ring strain associated with
      the skeleton of this natural product, we utilized 1R-5S-bicyclo[3.1.0]hexan-2-one
      as the starting material and developed two novel approaches to accomplish the
      enantioselective total synthesis of the C4 epimer of galiellalactone in 5 and 7
      steps, respectively, which capitalized on an efficient radical
      cyclization/fragmentation cascade reaction. Furthermore, an activity-based probe
      of 4-epi-galiellalactone with a terminal alkyne tag was successfully prepared to
      enable the experiments of activity-based protein profiling (ABPP). Through
      western blot and proteomic analysis, we not only confirmed the known target
      STAT3, but also identified a new target protein ataxin-7, which formed a covalent
      bond with the probe in intact cells via the Cys-129 residue.

PMID- 30183049
TI  - Metallome of cerebrovascular endothelial cells infected with Toxoplasma gondii
      using MU-XRF imaging and inductively coupled plasma mass spectrometry.
AB  - In this study, we measured the levels of elements in human brain microvascular
      endothelial cells (ECs) infected with T. gondii. ECs were infected with
      tachyzoites of the RH strain, and at 6, 24, and 48 hours post infection (hpi),
      the intracellular concentrations of elements were determined using a synchrotron
      microfocus X-ray fluorescence microscopy (MU-XRF) system. This method enabled the
      quantification of the concentrations of Zn and Ca in infected and uninfected
      (control) ECs at sub-micron spatial resolution. T. gondii-hosting ECs contained
      less Zn than uninfected cells only at 48 hpi (p < 0.01). The level of Ca was not
      significantly different between infected and control cells (p > 0.05).
      Inductively Coupled Plasma Mass Spectrometry (ICP-MS) analysis revealed infection
      specific metallome profiles characterized by significant increases in the
      intracellular levels of Zn, Fe, Mn and Cu at 48 hpi (p < 0.01), and significant
      reductions in the extracellular concentrations of Co, Cu, Mo, V, and Ag at 24 hpi
      (p < 0.05) compared with control cells. Zn constituted the largest part (74%) of
      the total metal composition (metallome) of the parasite. Gene expression analysis
      showed infection-specific upregulation in the expression of five genes, MT1JP,
      MT1M, MT1E, MT1F, and MT1X, belonging to the metallothionein gene family. These
      results point to a possible correlation between T. gondii infection and increased
      expression of MT1 isoforms and altered intracellular levels of elements,
      especially Zn and Fe. Taken together, a combined MU-XRF and ICP-MS approach is
      promising for studies of the role of elements in mediating host-parasite
      interaction.

PMID- 30183051
TI  - Lift-off cell lithography for cell patterning with clean background.
AB  - We developed a highly efficient method for patterning cells by a novel and simple
      technique called lift-off cell lithography (LCL). Our approach borrows the key
      concept of lift-off lithography from microfabrication and utilizes a fully
      biocompatible process to achieve high-throughput, high-efficiency cell patterning
      with nearly zero background defects across a large surface area. Using LCL, we
      reproducibly achieved >70% patterning efficiency for both adherent and non
      adherent cells with <1% defects in undesired areas.

PMID- 30183052
TI  - Aspalathus linearis (Rooibos) - a functional food targeting cardiovascular
      disease.
AB  - Increasing consumer bias toward natural products and the considerable wealth of
      indigenous knowledge has precipitated an upturn in market-driven research into
      potentially beneficial medicinal plants. In this context, Aspalathus linearis
      (Rooibos) has been identified to be a promising candidate which may impact
      cardiovascular disease (CVD), which is one of the most widely studied chronic
      diseases of modern times. Despite these efforts, ischemic heart disease remains
      the number one cause of mortality globally. Apart from genetic predisposition and
      other aetiological mechanisms specific to particular types of CVD, co-factors
      from interlinked systems contribute significantly to disease development and the
      severity of its clinical manifestation. The bioactivity of Rooibos is directed
      towards multiple therapeutic targets. Experimental data to date include
      antioxidant, anti-inflammatory and anti-diabetic effects, as well as modulatory
      effects in terms of the immune system, adrenal steroidogenesis and lipid
      metabolism. This review integrates relevant literature on the therapeutic
      potential of Rooibos in the context of CVD, which is currently the most common of
      non-communicable diseases. The therapeutic value of whole plant extracts versus
      isolated active ingredients are addressed, together with the potential for
      overdose or herb-drug interaction. The body of research undertaken to date
      clearly underlines the benefits of Rooibos as both preventative and complementary
      therapeutic functional food in the context of CVD.

PMID- 30183053
TI  - Effects of the suspended sediment concentration and oil type on the formation of
      sunken and suspended oils in the Bohai Sea.
AB  - The unsourced oil contamination on the coast of Bohai Sea has recently attracted
      scholars to study the formation of sunken and suspended oils (SSO) from oil
      slicks on the sea surface. In this research, batch experiments have been
      conducted to study the time-scale effect of the different concentrations of
      suspended sediments on the formation of sunken oils and suspended oils using
      three oils (Oman crude oil, Merey crude oil, and 380# fuel oil) and two sediments
      (sand and silt) at different temperatures. The results showed that the sunken and
      suspended oils formed quickly within the mixing time and reached a maximum at the
      equilibrium time, te, and that te had a wide range of variation with sediment
      concentration and type. The oil sinking and submerging efficiency could reach up
      to 6.33%, 43.82% and 44.44% for 380# fuel oil, Oman crude oil and Merey crude
      oil, respectively. It is noted that the increase in sediment concentration and
      environmental temperature could enhance the formation of SSO but that it had a
      close relationship with the oil type. Overall, hydrophobic sand had a
      significantly higher oil sedimentation effect than silt.

PMID- 30183050
TI  - Development and application of human skeletal muscle microphysiological systems.
AB  - A number of major disease states involve skeletal muscle, including type 2
      diabetes, muscular dystrophy, sarcopenia and cachexia arising from cancer or
      heart disease. Animals do not accurately represent many of these disease states.
      Human skeletal muscle microphysiological systems derived from primary or induced
      pluripotent stem cells (hPSCs) can provide an in vitro model of genetic and
      chronic diseases and assess individual variations. Three-dimensional culture
      systems more accurately represent skeletal muscle function than do two
      dimensional cultures. While muscle biopsies enable culture of primary muscle
      cells, hPSCs provide the opportunity to sample a wider population of donors.
      Recent advances to promote maturation of PSC-derived skeletal muscle provide an
      alternative to primary cells. While contractile function is often measured in
      three-dimensional cultures and several systems exist to characterize contraction
      of small numbers of muscle fibers, there is a need for functional measures of
      metabolism suited for microphysiological systems. Future research should address
      generation of well-differentiated hPSC-derived muscle cells, enabling muscle
      repair in vitro, and improved disease models.

PMID- 30183054
TI  - Physical behaviour is weakly associated with physical fatigue in persons with
      multiple sclerosis-related fatigue.
AB  - BACKGROUND: Fatigue affects 80% of persons with multiple sclerosis and is
      associated with daily physical functioning. Both fatigue and physical behaviour
      are multidimensional concepts. OBJECTIVE: To study the association between the
      dimensions of physical behaviour and multiple sclerosis-related fatigue. METHODS:
      Cross-sectional analysis of 212 persons with multiple sclerosis. Participants
      were severely fatigued, with a Fatigue Severity Scale median (interquartile
      range): 5.4 (4.8-5.9) and were minimally to moderately neurologically impaired,
      based on the Expanded Disability Status Scale: 2.5 (2.0-3.5), 73% had relapsing
      remitting multiple sclerosis. Fatigue was measured by questionnaires (i.e.
      Checklist Individual Strength, Modified Fatigue Impact Scale), and the dimensions
      subjective, physical, cognitive and psychological fatigue were distinguished.
      Physical behaviour was measured using an Actigraph GT3X+, and outcomes were
      categorized into the dimensions of activity amount, activity intensity, day
      pattern, and distribution of activities. RESULTS: The physical behaviour
      dimensions were significantly associated with only the physical fatigue dimension
      (omnibus F-test: 3.96; df1 = 4, df2 = 207; p = 0.004). Additional analysis showed
      that the amount of activity (unstandardized beta coefficient (beta) = -0.16; 95%
      confidence interval (CI) -0.27 to -0.04; p = 0.007), activity intensity (beta = 
      0.18; 95% CI -0.31 to -0.06; p = 0.004) and day pattern of activity (beta = 
      0.17; 95% CI, -0.28 to -0.06; p = 0.002) were the physical behaviour dimensions
      that were significantly associated with physical fatigue. CONCLUSION: Physical
      behaviour is weakly associated with physical fatigue and is not associated with
      other dimensions of fatigue.

PMID- 30183056
TI  - Intergluteal Contour Deformity in Hidradenitis Suppurativa.

PMID- 30183055
TI  - Exoskeleton gait training after spinal cord injury: An exploratory study on
      secondary health conditions.
AB  - OBJECTIVE: To explore changes in pain, spasticity, range of motion, activities of
      daily living, bowel and lower urinary tract function and quality of life of
      individuals with spinal cord injury following robotic exoskeleton gait training.
      DESIGN: Prospective, observational, open-label multicentre study. METHODS: Three
      training sessions per week for 8 weeks using an EksoTM GT robotic exoskeleton
      (EKSO Bionics). Included were individuals with recent (<1 year) or chronic (>1
      year) injury, paraplegia and tetraplegia, complete and incomplete injury, men and
      women. RESULTS: Fifty-two participants completed the training protocol. Pain was
      reported by 52% of participants during the week prior to training and 17% during
      training, but no change occurred longitudinally. Spasticity decreased after a
      training session compared with before the training session (p <0.001), but not
      longitudinally. Chronically injured participants increased Spinal Cord
      Independence Measure (SCIM III) from 73 to 74 (p = 0.008) and improved life
      satisfaction (p = 0.036) over 8 weeks of training. Recently injured participants
      increased SCIM III from 62 to 70 (p < 0.001), but no significant change occurred
      in life satisfaction. Range of motion, bowel and lower urinary function did not
      change over time. CONCLUSION: Training seemed not to provoke new pain. Spasticity
      decreased after a single training session. SCIM III and quality of life increased
      longitudinally for subsets of participants.

PMID- 30183057
TI  - Prediction for return to driving after the first-ever stroke in Korea: The KOSCO
      study.
AB  - OBJECTIVE: To identify contributing factors that can be used to predict which
      patients with first-ever stroke will return to driving during 1 year after
      stroke. DESIGN: Multicentre cohort study. SUBJECTS: A total of 620 first-ever
      stroke patients who drove before stroke. METHODS: The Stroke Cohort for
      Functioning and Rehabilitation is a large, multicentre, prospective cohort study
      of all patients with acute first-ever stroke admitted to participating hospitals
      in 9 areas of Korea. This study analysed the data from 1,354 patients who
      completed a face-to-face survey about return to driving at 1 year after stroke. A
      multiple binary logistic regression analysis model was used to analyse factors
      that potentially influenced return to driving during 12 months after stroke.
      RESULTS: Of 620 subjects, 410 (66.1%) returned to driving after stroke. They
      resumed driving at a mean of 2.15 months after stroke (standard deviation 2.32
      years). Regression models showed that sex, age, modified Rankin scale (mRS),
      education about return to driving, and Fugl-Meyer Assessment (FMA) were
      significantly related to return to driving. Stroke type, ambulatory function, and
      language function at 7 days were not correlated with return to driving.
      CONCLUSION: Male patients, education about return to driving, lower mRS, and
      higher FMA at 7 days after stroke are predictors of return to driving. This model
      could be used by clinicians to help counsel patients and their families.

PMID- 30183058
TI  - Mature congenital intraneural teratoma in cerebellum of pig.
AB  - The biological behavior of teratomas depends on several interdependent clinical
      and epidemiological variables such as age at diagnosis, sex, tumor
      microenvironment, and tumor morphology, among others. All these variables are
      correlated to different cytogenetic and molecular aberrations (Harms et al,
      2006). There are null reports of teratomas in pigs. The aim of this study was to
      characterize the tissues present in a mature congenital intraneural teratoma in
      the cerebellum area of a Landrace female pig of 6-7 weeks old. In this study,
      tissue control samples were used to validate each staining method. Sections from
      the teratoma showed normal histology of the cerebellum, including rounded
      Purkinje neurons with abundant cytoplasm, euchromatic nuclei, and prominent
      nucleoli; glial cells with a scarce amount of cytoplasm and small and highly
      basophile-nuclei (compact chromatin) and axonal tracts (white matter).
      Interestingly, we also observed areas with tissues different from the nervous
      tissue, including bundles of well-defined skeletal muscle fibers with a striated
      pattern and peripheral nuclei; hyaline cartilage plaques, with prominent presence
      of chondrocytes in their lagoons forming isogenous groups surrounded by a
      territorial and interterritorial matrix; trabeculated bone tissue; and
      adipocytes, which are ring-shaped cells with peripheral flattened nuclei, as a
      result of the presence of a central large lipid droplet. To our knowledge, this
      study is the first to describe a congenital intraneural mature teratoma in the
      cerebellum of a pig.

PMID- 30183059
TI  - [Children's and adolescents' perception of their quality of life in cases of
      attention deficit hyperactivity disorder with and without pharmacological
      treatment and in controls].
AB  - INTRODUCTION: Health-related quality of life perceived by children and teenagers
      is important to assess the effects of therapeutic intervention. AIM: To analyze
      quality of life, comparing cases of attention deficit hyperactivity disorder
      (ADHD) treated with methylphenidate, untreated cases and controls. SUBJECTS AND
      METHODS: Sampling of 228 participants between 8 and 14 years-old. Consecutive
      sampling in ADHD according to DSM-IV criteria (ADHD Rating Scales IV) and random
      sampling of matched controls by sex and age. Evaluation of quality of life using
      KIDSCREEN-52 (children version). ANOVA with Bonferroni correction was used.
      RESULTS: There is a moderate significant correlation between greater intensity of
      ADHD symptoms and worse quality of life, except in the dimension of physical well
      being. Cases of untreated ADHD have significantly worse quality of life than
      controls on psychic well-being, mood, autonomy school environment and social
      acceptance. Cases of treated ADHD present similar results, except in the school
      environment and psychological well-being. The cases of ADHD treated only differ
      significantly from ADHD not treated in having a better school environment.
      CONCLUSIONS: The cases of ADHD present dimensions of KIDSCREEN-52 with worse
      quality of life than controls and the cases of ADHD treated with methylphenidate
      only differ significantly from those not treated in presenting better results in
      the school environment.

PMID- 30183060
TI  - [The most frequent causative agents of Guillain-Barre syndrome in a Mexican
      general hospital].
AB  - INTRODUCTION: After Zika virus outbreak and the increase in the incidence of
      Guillain-Barre syndrome (GBS), the causal relationship has been studied, however
      a full etiological correlation has not been found. PATIENTS AND METHODS: From
      January 1 to December 31, 2017, patients with GBS were included. In addition to
      the basic serologies, enterovirus, herpes, Campylobacter, hepatitis B and C,
      TORCH, HIV, Brucella and Salmonella were requested. RESULTS: Cohort of seven male
      patients. Five patients analyzed cerebrospinal fluid reporting normal; all of
      them underwent brain scan, reporting normal. Neuroconduction was performed,
      resulting in acute inflammatory demyelinating polyneuropathy in four cases and
      acute motor axonal neuropathy in one case. All received intravenous
      immunoglobulins, five cases had a good prognosis and two deaths. No positive
      cases were reported to Zika virus. A positive case was reported to dengue and
      another to chikungunya. Five positive cases were reported to Campylobacter. One
      case positive to enterovirus. Dengue + Campylobacter coinfections were reported
      in one case and chikungunya + Campylobacter in another case. CONCLUSIONS: The
      present cohort shows that it was not possible to establish a causal relationship
      between GBS and Zika virus, but other viral and bacterial causal agents were
      identified, such as dengue, chikungunya and enterovirus, with the identification
      of Campylobacter cases even more remarkable.

PMID- 30183061
TI  - [Bilateral acute subdural haematoma without subarachnoid haemorrhage secondary to
      rupture of an anterior communicating aneurysm. A case report and review of the
      literature].
AB  - INTRODUCTION: Pure acute subdural haematomas caused by aneurysmal rupture are a
      highly infrequent event, with only 51 cases published in the literature to date,
      with only six cases due to the rupture of anterior communicating artery aneurysm.
      AIM: To describe a case of an acute subdural haematoma not associated with
      subarachnoid haemorrhage due to ruptured of an anterior communicating cerebral
      artery aneurysm. CASE REPORT: A 55-year-old woman without a traumatic history,
      who is found at home with a level of consciousness of 4 points on the Glasgow
      Coma Scale and a bilateral arreactive mydriasis, which are reversed with medical
      measures. Cranial CT shows an acute bi-hemispherical convexity and
      interhemispheric subdural haematoma with no evidence of associated subarachnoid
      haemorrhage. The angio-CT reveals an anterior communicating artery aneurysm. We
      proceed to urgent embolization of the aneurysm. The patient was admitted to the
      Intensive Care Unit, where intracranial pressure is monitored and controlled
      initially with medical treatment. Patient outcome was unfavorable, confirming in
      the control CT scan coincident with an increase of uncontrolled medically
      intracranial hypertension, established ischemic infarctions areas, which made any
      surgical treatment non-viable. CONCLUSION: In the case of an acute subdural
      haematoma without subarachnoid haemorrhage nor traumatic brain injury or its
      external stigmas, we must consider the rupture of a cerebral aneurysm as a
      possible cause. Likewise, the initial management of the acute subdural haematoma
      in patients with poor neurological condition should be priority and surgical.

PMID- 30183062
TI  - [Model of executive functions based on factorial analyses in child and school
      populations: a meta-analysis].
AB  - INTRODUCTION: Executive functions are defined as a set of skills that are
      involved in various activities which are novel to the individual and which
      require a creative solution. It is not easy or straight forward to conceptualise
      or identify the factors that make up a population of young children. AIM: To
      analyse the components of executive function due to the clinical implications in
      different neurodevelopmental disorders in a population-based sample of young
      children. DEVELOPMENT: From the body of literature, 35 published papers that used
      different factor analysis approaches for factor extraction were reviewed. The
      probability of a study with three factors being undertaken in the stage between 0
      to 12 years is 1.44 times higher than studies being undertaken with some focus on
      another structure. The probability of a study being undertaken that focuses on
      the Flexibility dimension in the stage between 0 to 12 years is 1.45 times higher
      than a study being undertaken that focuses on any other dimension. The
      association between the different structures and dimensions that are analysed
      with respect to age using the Kendall tau-b indicates a statistically significant
      association between: studies with three factors and age (tau = 0.29; p = 0.044)
      and flexibility with age (tau = 0.37; p = 0.012). CONCLUSIONS: The diversity of
      the obtained results can be attributed to, and is in line with, the plurality of
      theoretical conceptualisations, tests used and statistical analyzes carried out.
      It can be concluded that working memory, inhibition and flexibility are the
      executive processes most commonly found in the factorial models of executive
      control in young children and adolescents.

PMID- 30183063
TI  - [XXXII Reunion Anual de la Sociedad Andaluza de Neurofisiologia Clinica.
      Communications].

PMID- 30183064
TI  - [TK2 mutations and late onset myopathy: first description in a Mexican patient].

PMID- 30183065
TI  - Adverse effects of topical photodynamic therapy: a consensus review and approach
      to management.
AB  - BACKGROUND: Topical photodynamic therapy (PDT) is widely used to treat
      superficial nonmelanoma skin cancer and dysplasia, and is generally well
      tolerated. However, as with all treatments, adverse effects may occur and
      awareness may facilitate approaches to prevention and management. OBJECTIVES: To
      review the available evidence relating to the adverse effects of topical PDT, to
      help inform recommendations in updated clinical guidelines produced by the
      British Association of Dermatologists and British Photodermatology Group, and the
      efficacy of preventative and therapeutic approaches. METHODS: This review
      summarizes the published evidence related to the adverse effects of topical PDT
      and attempts to interpret this evidence in the context of patient risk and
      management. RESULTS: Pain and discomfort during PDT are acute adverse effects,
      which can be minimized through the use of modified and low-irradiance PDT
      regimens and do not therefore usually limit successful treatment delivery. Other
      adverse effects include the risk of contact allergy to photosensitizer prodrugs,
      although this is rare but should be kept in mind, particularly for patients who
      have received multiple PDT treatments to larger areas. There are no other
      significant documented longer-term risks and, to date, no evidence of cumulative
      toxicity or photocarcinogenic risk. CONCLUSIONS: Topical PDT is usually well
      tolerated, reinforcing the utility of this important therapeutic option in
      dermatology practice. The main acute adverse effect of pain can typically be
      minimized through preventative approaches of modified PDT regimens. Other adverse
      effects are uncommon and generally do not limit treatment delivery.

PMID- 30183066
TI  - Cardiovascular Morbidity and Risk Factors in Holocaust Survivors in Israel.
AB  - OBJECTIVES: To compare the prevalence of cardiovascular diseases and risk factors
      in Holocaust survivors with that of Jewish immigrants from Europe and America.
      DESIGN: Population-based, cross-sectional study. SETTING: Clalit, a large Israeli
      healthcare provider. PARTICIPANTS: Holocaust survivors (n=83,971) and a
      comparison group of Jewish individuals born in North or South America or European
      countries not under Nazi occupation or who immigrated to Israel before 1939
      (n=16,058) (mean age 84+/-7, 61% female) MEASUREMENTS: Univariate and
      multivariable logistic regression analyses of cardiovascular diseases and risk
      factors. Matching the comparison group to Holocaust Survivors on propensity
      scores for exposure. RESULTS: The prevalence of ischemic heart disease (38.7% vs
      31.3%), congestive heart failure (10.9% vs 9.1%), past stroke (15.7% vs 13.4%),
      and peripheral vascular disease (9.5% vs 7.9%) was higher in Holocaust survivors
      (p<.001 for all comparisons). Similar results were found for cardiovascular risk
      factors (diabetes mellitus (14.4% vs 13.6%), hypertension (89.3% vs 86.4%),
      dyslipidemia (75.9% vs 74.0%) (p<.001 for all comparisons). In multivariable
      analysis, matched on propensity scores and controlled for confounders, odds
      ratios for men and women were higher for diabetes (1.23, 1.55), dyslipidemia
      (1.53, 1.51), hypertension (1.56 , 1.94), stroke (1.18, 1.17), and ischemic heart
      disease (1.18, 1,40), but not congestive heart failure (0.95, 1.02). A Positive
      association was noted for peripheral vascular disease in males (1.20) but not
      females (0.96). CONCLUSION: Prevalence of cardiovascular diseases and risk
      factors was higher in Holocaust survivors. These associations were stronger in
      women in most cases.

PMID- 30183067
TI  - Acute exacerbation of carpal tunnel syndrome after Radiesse(r) injection for hand
      rejuvenation.

PMID- 30183068
TI  - Psychosocial impact of skin biopsies in the setting of melanoma screening: a
      cross-sectional survey.

PMID- 30183069
TI  - An open-label phase 2 trial of entospletinib in indolent non-Hodgkin lymphoma and
      mantle cell lymphoma.
AB  - Spleen tyrosine kinase (Syk) mediates B-cell receptor signalling in normal and
      malignant B cells. Entospletinib is an oral, selective Syk inhibitor.
      Entospletinib monotherapy was evaluated in a multicentre, phase 2 study of
      patients with relapsed or refractory indolent non-Hodgkin lymphoma or mantle cell
      lymphoma (MCL). Subjects received 800 mg entospletinib twice daily. Forty-one
      follicular lymphoma (FL), 17 lymphoplasmacytoid lymphoma/Waldenstrom
      macroglobulinaemia (LPL/WM), 17 marginal zone lymphoma (MZL) and 39 MCL patients
      were evaluated. The primary endpoint was a progression-free survival (PFS) rate
      (defined as not experiencing progression or death) at 16 weeks for patients with
      MCL and at 24 weeks for patients with FL, LPL/WM and MZL. The most common
      treatment-emergent adverse events were fatigue, nausea, diarrhoea, vomiting,
      headache and cough. Common laboratory abnormalities were anaemia, neutropenia and
      thrombocytopenia; aspartate transaminase, alanine transaminase, total bilirubin
      and serum creatinine were all increased. PFS at 16 weeks in the MCL cohort was
      63.9% [95% confidence interval (CI) 45-77.8%]; PFS at 24 weeks in the FL, LPL/WM,
      MCL and MZL cohorts was 51.5% (95% CI 32.8-67.4%), 69.8% (95% CI 31.8-89.4%),
      56.6% (95% CI 37.5-71.8%) and 46.2% (95% CI 18.5-70.2%), respectively.
      Entospletinib had limited single-agent activity with manageable toxicity in these
      patient populations.

PMID- 30183070
TI  - The use of direct oral anticoagulants in chronic kidney disease.
AB  - Increasing use of direct oral anticoagulants (DOACs) has made management of non
      valvular atrial fibrillation and venous thromboembolism easier in most patients.
      But the presence of co-existing renal impairment could render the use of DOACs
      problematic because all of these drugs have varying degrees of renal excretion.
      In this paper we address misconceptions about the safety and efficacy of DOACs in
      moderate-severe renal impairment by presenting a summary of the literature from
      phase III trials and real-world studies. It also addresses the important
      consideration of correct estimate of renal function for DOAC dosing. It is hoped
      that the review will serve as a valuable resource for clinicians involved in
      anticoagulation decision-making in patients with renal impairment to guide the
      choice of most suitable agent. Accurate dosing is of particular relevance as
      registry data suggests it is done inconsistently and may be resulting in
      avoidable thromboembolic and bleeding events.

PMID- 30183071
TI  - NLRP2 negatively regulates antiviral immunity by interacting with TBK1.
AB  - Nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) are
      intracellular pattern recognition receptors (PRRs) that regulate a variety of
      inflammatory and host defense responses. Unlike the well-established NLRs, the
      roles of NLRP2 are controversial and poorly defined. Here, we report that NLRP2
      acts as a negative regulator of TANK-binding kinase 1 (TBK1)-mediated type I
      interferon (IFN) signaling. Mechanistically, NLRP2 interacted directly with TBK1,
      and this binding disrupted the interaction of TBK1 and interferon regulatory
      factor 3 (IRF3), which interfered with TBK1-induced IRF3 phosphorylation. IFNs
      induce a series of proteins that have well-known antiviral or immune-regulatory
      functions, and tight control of the IFN signaling cascade is critical for
      limiting tissue damage and preventing autoimmunity. Our studies indicate that the
      NLRP2-TBK1 axis may serve as an additional signaling cascade to maintain immune
      homeostasis in response to viral infection.

PMID- 30183072
TI  - Skin involvement by chronic lymphocytic leukaemia is frequently associated with
      unrelated neoplastic or inflammatory cutaneous disease and is not indicative of
      general disease progression.

PMID- 30183073
TI  - Rapalog combined with CCR4 antagonist improves anticancer vaccines efficacy.
AB  - mTOR pathway inhibitors such as rapalogs represent a promising tool to induce
      functional memory CD8 T cells. In our study, we investigated the combination of
      temsirolimus with anticancer vaccines. Using various designs of cancer vaccines
      (short and long peptides or the B subunit of Shiga toxin as an antigen delivery
      vector) and tumor models (melanoma, lung and colon cancer), we showed that the
      administration of temsirolimus efficiently decreased tumor growth and enhanced
      tumor-specific CD8 T-cell responses induced by vaccination. Furthermore, tumor
      specific CD8 T cells induced by the bi-therapy (vaccine + temsirolimus) exhibit
      phenotypic characteristics of central memory (CD127+ CD62L+ ) CD8 T cells
      compared to vaccination alone. We demonstrated that regulatory CD4 T cells (Tregs
      ) expansion in vivo limits the efficacy of the bi-therapy by altering the
      antitumor CD8 T-cell responses. Finally, the use of a small molecule CCR4
      antagonist to prevent Tregs induction considerably improved the efficacy of the
      bi-therapy by enhancing CD8 T cells-mediated antitumor immunity. Taken together,
      our study highlights the potential interest of combining cancer vaccines with
      drugs that promote memory CD8 T cells and inhibit Tregs .

PMID- 30183074
TI  - Murine eosinophil development and allergic lung eosinophilia are largely
      dependent on the signaling adaptor GRB2.
AB  - Eosinophils are innate effector cells associated with allergic inflammation.
      Their development and survival is largely dependent on IL-5 and the common beta
      chain (betac ) of the IL-5 receptor that serves as docking site for several
      proteins that mediate down-stream signaling cascades including JAK/STAT, PI3
      kinase, NFkappaB, and RAS-MAP kinase pathways. The relative contribution of these
      signaling pathways for eosinophil development and homeostasis in vivo are poorly
      understood. Here, we investigated the role of GRB2, an adaptor protein that binds
      to betac and other proteins and elicits the RAS-MAP kinase pathway. By using GRB2
      inhibitors and inducible deletion of the Grb2 gene in mouse eosinophils we
      demonstrate that GRB2 plays a critical role for development of eosinophils from
      bone marrow precursors. Furthermore, Aspergillus fumigatus-induced allergic lung
      eosinophilia was significantly reduced in mice with induced genetic deletion of
      Grb2. Our results indicate that GRB2 is important for eosinophil development in
      steady-state conditions and during allergic inflammation. Based on these findings
      pharmacologic GRB2 inhibitors may have the potential to dampen tissue
      eosinophilia in various eosinophil-associated diseases.

PMID- 30183075
TI  - Molecular and health effects in the upper respiratory tract associated with
      tobacco smoking other than cigarettes.
AB  - The objective of the review was to compare molecular and health effects of
      tobacco smoking using cigars, cigarillos, pipe and water pipe in relation to the
      effects of cigarette smoking. In this review we will focus on the upper
      respiratory tract. Mechanisms of interaction of tobacco smoke constituents after
      products other than cigarettes are similar to these associated with cigarette
      smoking. Carcinogenic activity was demonstrated for any type of tobacco smoking,
      although the risk of developing head and neck squamous cell carcinoma (HNSCC)
      remains lower in users of cigars, traditional pipe and water pipe as compared to
      cigarette smoking. Nevertheless, there is no way of safe tobacco smoking.

PMID- 30183076
TI  - Histone demethylase KDM7A controls androgen receptor activity and tumor growth in
      prostate cancer.
AB  - Prostate cancer can be controlled by androgen-hormone treatment until the cancer
      becomes refractory. It is believed that hormone sensitivity is largely dependent
      on androgen receptor (AR) activity. Here, we found the histone demethylase KDM7A
      which demethylates histone H3K27 to be overexpressed in enzalutamide resistant
      castration-resistant prostate cancer cell line C4-2b, and investigated the
      molecular mechanism whereby androgen receptor activity is regulated by KDM7A. We
      engineered AR-positive LNCaP cells to stably express a short-hairpin RNA against
      KDM7A mRNA from a lentiviral vector. By measuring AR downstream gene expression
      after androgen stimulation, we found that a KDM7A-deficient cell line showed
      lower AR downstream gene expression compared to a control cell. KDM7A knock-down
      in LNCaP cell line caused decreased cell proliferation. Western blot analysis
      with modified-histone antibody revealed that the KDM7A-knock-down LNCaP cell line
      had increased H3K27 di-methylation. We confirmed KDM7A binding on AR target-gene
      promoters after hormone stimulation in chromatin-immunoprecipitation experiments.
      And increased H3K27 di-methylation was observed in KDM7A knock-down LNCaP stable
      cell. Treatment with KDM7A inhibitor, TC-E 5002, reduced proliferation and
      induced apoptosis of prostate cancer cells. Finally, we observed that the KDM7A
      protein was significantly upregulated in prostate cancer tissue, and that this
      difference correlated with the Gleason score. These data suggested that KDM7A is
      potentially a good therapeutic target for prostate cancer drugs and can be used
      as potentially a good prognostic indicator for prostate cancer and related
      treatment strategies.

PMID- 30183077
TI  - Clonal evolution in long-term follow-up patients with hepatocellular carcinoma.
AB  - To investigate tumor clonal evolution in hepatocellular carcinoma (HCC), we
      collected 31 tumor samples,16 peritumor samples and matched PBMCs from 11 long
      term follow-up patients with HCC. Whole-exome sequencing was performed to obtain
      SNVs and CNVs for each sample. An average of 652.2 somatic mutations were
      identified in each patient and the mean percentage of nonubiquitous tumor
      mutations was 63.7% (range, 0.7%-100%), reflecting the variety of tumor
      heterogeneity. Further analysis of clonal evolution was conducted based on
      mutation clustering results and revealed that different clonal evolution patterns
      indeed existed in single and multifocal HCC while these patterns were
      significantly correlated to patients' clinical course. These patterns clearly
      demonstrated different mechanisms of tumor recurrence. During tumor clonal
      evolution, potential therapeutic targets also emerged and vanished dynamically.
      Moreover, mutation analysis revealed that the contribution of mutational
      signature was correlated with clonal evolution history. Target sequencing of
      follow-up plasma samples also confirmed that ctDNA level could dynamically
      reflect tumor clonal/subclonal burden. By investigating clonal evolution in HCC
      patients, our analysis revealed that different patterns indeed existed during HCC
      progression and proposed a novel strategy for identifying the origin of recurrent
      tumor as well as optimizing treatment selection.

PMID- 30183078
TI  - Proteogenomic systems analysis identifies targeted therapy resistance mechanisms
      in EGFR-mutated lung cancer.
AB  - Cancer precision medicine largely relies on knowledge about genetic aberrations
      in tumors and next-generation-sequencing studies have shown a high mutational
      complexity in many cancers. Although a large number of the observed mutations is
      believed to be not causally linked with cancer, the functional effects of many
      rare mutations but also of combinations of driver mutations are often unknown.
      Here, we perform a systems analysis of a model of EGFR-mutated nonsmall cell lung
      cancer resistant to targeted therapy that integrates whole exome sequencing,
      global time-course discovery phosphoproteomics and computational modeling to
      identify functionally relevant molecular alterations. Our approach allows for a
      complexity reduction from over 2,000 genetic events potentially involved in
      mediating resistance to only 44 phosphoproteins and 35 topologically close
      genetic alterations. We perform single- and combination-drug testing against the
      predicted phosphoproteins and discovered that targeting of HSPB1, DBNL and AKT1
      showed potent antiproliferative effects overcoming resistance against EGFR
      inhibitory therapy. Our approach may therefore be used to complement mutational
      profiling to identify functionally relevant molecular aberrations and propose
      combination therapies across cancers.

PMID- 30183079
TI  - "I'm Kind of a Feminist": Using Master Narratives to Analyze Gender Identity in
      Middle Childhood.
AB  - A robust literature documents the significance of gender in children's
      development, but gaps remain in understanding how developing gender identities
      link to gender inequalities. This article uses master narratives to analyze the
      ways that children's gender narratives reinforce or disrupt gender inequality.
      Semistructured interviews were conducted with 233 Black, White, mixed- and other
      race minority children (7-12 years old; Mage  = 9.92; 61% girls) in racially
      diverse schools in the Pacific Northwest. Four narrative types were identified:
      two "master narratives" that reinforced gender inequality and two "alternative
      narratives" that disrupted it. Analyses revealed that 5th/6th-graders (vs. 2nd
      4th graders) and girls (vs. boys) were more likely to tell alternative
      narratives. The contributions of master narratives for understanding gender
      identity, development, and inequality are discussed.

PMID- 30183080
TI  - Plasma C-peptide and glycated albumin and subsequent risk of cancer: From a large
      prospective case-cohort study in Japan.
AB  - To elucidate the individual impacts of insulin and blood glucose on cancer risk,
      we investigated the association of plasma C-peptide, a surrogated marker of
      insulin and glycated albumin (GA), a more stable marker of blood glucose, with
      all-site and site-specific cancer risk by mutually accounting for their
      confounding effects. The study was prospectively conducted with nearly 4,000
      cancer cases arising in our population-based cohort of 33,736 subjects who
      answered the baseline questionnaire and supplied blood samples. After exclusion
      of subjects with apparent DM, analysis was done in 3,036 cancer cases and 3,667
      subcohort subjects. Among men and women combined, highest levels of C-peptide
      were statistically significantly associated with an increased risk of all-site
      [Hazard ratio (HR): 1.21; 95% confidence interval: 1.02-1.42], colon [1.73; 1.20
      2.47], liver [3.23; 1.76-5.91], kidney, renal pelvis and ureter cancers [2.47;
      1.07-5.69], compared to the respective lowest levels, after adjustment for GA
      levels. Among these C-peptide-related cancers, colon and liver cancers also
      showed an increased risk associated with elevated GA levels independently of C
      peptide levels. The corresponding HRs for colon and liver cancers compared to the
      highest and lowest GA levels were 1.43 [1.02-2.00] and 2.02 [1.15-3.55],
      respectively. Effect modification by gender was only evident for the association
      between C-peptide and colon cancer (p for interaction = 0.04). Higher insulin
      levels, independently of higher blood glucose levels, may be relevant to DM
      related carcinogenesis for several cancer sites. Examination of circulating
      insulin levels is a plausible option in evaluating cancer risk even in
      individuals who have not developed DM.

PMID- 30183081
TI  - Organ involvement occurs in all forms of hereditary haemolytic anaemia.

PMID- 30183082
TI  - TP53 mutations are associated with mutated MYD88 and CXCR4, and confer an adverse
      outcome in Waldenstrom macroglobulinaemia.
AB  - Little is known about TP53 mutations in Waldenstrom Macroglobulinaemia (WM). We
      evaluated 265 WM patients for TP53 mutations by next-generation sequencing, and
      validated the findings by Sanger sequencing. TP53 mutations were identified and
      validated in 6 (2.6%) patients that impacted the DNA-binding domain. All six were
      MYD88- and CXCR4-mutated. Ibrutinib showed activity in patients carrying all
      three mutations. With a median follow-up of 18 months, 2 (33%) with biallelic
      TP53 inactivation died of progressive disease. TP53 mutations are rare in WM, and
      associate with MYD88 and CXCR4 mutations. WM patients with TP53 mutations show
      response to ibrutinib.

PMID- 30183083
TI  - Consumption of red and processed meat and breast cancer incidence: A systematic
      review and meta-analysis of prospective studies.
AB  - Prior studies on red and processed meat consumption with breast cancer risk have
      generated inconsistent results. We performed a systematic review and meta
      analysis of prospective studies to summarize the evidence regarding the relation
      of red meat and processed meat consumption with breast cancer incidence. We
      searched in MEDLINE and EMBASE databases through January 2018 for prospective
      studies that reported the association between red meat and processed meat
      consumption with incident breast cancer. The multivariable-adjusted relative risk
      (RR) was combined comparing the highest with the lowest category of red meat
      (unprocessed) and processed meat consumption using a random-effect meta-analysis.
      We identified 13 cohort, 3 nested case-control and two clinical trial studies.
      Comparing the highest to the lowest category, red meat (unprocessed) consumption
      was associated with a 6% higher breast cancer risk (pooled RR,1.06; 95%
      confidence intervals (95%CI):0.99-1.14; I2 = 56.3%), and processed meat
      consumption was associated with a 9% higher breast cancer risk (pooled RR, 1.09;
      95%CI, 1.03-1.16; I2 = 44.4%). In addition, we identified two nested case-control
      studies evaluating the association between red meat and breast cancer stratified
      by N-acetyltransferase 2 acetylator genotype. We did not observe any association
      among those with either fast (per 25 g/day pooled odds ratio (OR), 1.18; 95%CI,
      0.93-1.50) or slow N-acetyltransferase 2 acetylators (per 25 g/day pooled OR,
      0.99; 95%CI, 0.91-1.08). In the prospective observational studies, high processed
      meat consumption was associated with increased breast cancer risk.

PMID- 30183084
TI  - A new perspective: Exploring future therapeutic strategies for cancer by
      understanding the dual role of B lymphocytes in tumor immunity.
AB  - Our previous understanding of the role of B lymphocytes in tumor immunity is its
      antitumor effects. However, further evidence indicates B lymphocytes can also
      promote tumorigenesis by modulating immune responses. Therefore, the increasingly
      complex role of B lymphocytes in tumor immunity may become an important factor in
      tumor immunotherapy. In this review, we describe the development of B cells in
      tumor microenvironments. We then focus on the most controversial issues of the
      biological functions of B lymphocytes. Finally, we nominate B cells as
      therapeutic targets, which should open broad perspectives for the development of
      their clinical applications.

PMID- 30183085
TI  - Fingernail involvement in pemphigus and its correlation with disease severity and
      other clinicodemographic parameters.

PMID- 30183086
TI  - The width of the third ventricle associates with cognition and behaviour in motor
      neuron disease.
AB  - OBJECTIVES: An enlarged width of the third ventricle (WTV) has been described in
      amyotrophic lateral sclerosis (ALS) patients, although its clinical meaning is
      unknown. The aims of this study were to evaluate the contribution of
      demographical, clinical and genetic factors to the WTV in different motor neuron
      disease (MND) phenotypes and to assess its brain structural correlates. MATERIALS
      AND METHODS: The WTV was measured by transcranial ultrasound in 107 MND patients
      (82 diagnosed with classical ALS, 16 with progressive muscular atrophy and 9 with
      primary lateral sclerosis) and 25 controls. Genetic analysis, and neurological
      and neuropsychological examinations were performed in patients. Brain volumetric
      analysis of MR images was obtained in 85 patients. The association of WTV with
      demographical, clinical, genetic and neuropsychological variables as well as with
      brain volumes was assessed by multivariable models. RESULTS: Eighteen patients
      were diagnosed with genetic MND and 42.3% of patients showed executive or
      behavioural impairment (EBI). MND patients showed larger WTV than controls. The
      WTV was significantly associated with age, spinal onset and the presence of EBI,
      but not with the genetic background, the phenotype or disability. Greater WTV was
      also associated with reduced subcortical grey matter volume, but not with the
      cortical or the white matter volume. CONCLUSIONS: The enlargement of the WTV
      found in the different MND phenotypes is attributable to the subcortical grey
      matter atrophy and is associated with cognitive and behavioural impairment.
      Larger longitudinal studies are needed to determine its role as biomarker in MND
      patients with frontotemporal dementia.

PMID- 30183087
TI  - Genome-wide DNA methylation profiling of primary colorectal laterally spreading
      tumors identifies disease-specific epimutations on common pathways.
AB  - Colorectal laterally spreading tumors (LSTs) grow to extremely large size while
      rarely invade deeply. Also, there is a low tendency to become cancerous. We used
      the Illumina Human Methylation 450K array to query the main epigenetic difference
      of LSTs. We built a discovery cohort with 10 matched cases, and a validation
      cohort with 9 additional matched cases. Our results suggest that LST displays
      significant decrease in DNA methylation, highlighted by the discovery of 1,018
      hypomethylated intergenic regions (IGRs). Comparing to classic differentially
      methylated probes and regions that overlap transcription starting site and CpG
      island, IGR-regions were associated more closely with genes involved in
      functional biological processes and correlated with specific histone
      modifications. Hypomethylated IGR regions were often annotated as tissue-specific
      regulatory elements for noncolon tissues and were typically epigenetically
      silenced in normal colon mucosa. By integration of public data, we defined the
      commonality and specific epigenetic signatures for adenomas, LSTs and colon
      adenocarcinomas. Only 435 hypermethylated differentially methylated probes (DMPs)
      and differentially methylated regions (DMRs) and 517 hypomethylated DMPs and DMRs
      were shared by the three diseases. However, our pathway-level analysis discovered
      that genes in four pathways were common target of epimutations in LSTs, adenomas
      and CRCs. More interestingly, different diseases seem to employ distinct
      epigenetic insult to disturb specific pathways. Between LST and adenoma, we found
      eight pathways including Ras signaling and Rap1 signaling pathway were commonly
      targeted but the epimutation patterns were opposite. Comparison between
      precancerous conditions and invasive states revealed the key pathways governing
      the progression to malignancy, including PI3K-Akt pathways.

PMID- 30183088
TI  - Urinary cell-free microRNA biomarker could discriminate bladder cancer from
      benign hematuria.
AB  - The most common symptom of bladder cancer (BC) is hematuria. However, not all
      patients with hematuria are diagnosed with BC. Here, we explored a novel method
      to discriminate BC from hematuria under nonmalignant conditions by measuring
      differences in urinary cell-free microRNA (miRNA) expression between patients
      with BC and those with hematuria. A multicenter study was performed using 543
      urine samples obtained from the National Biobank of Korea, including 326 BC, 174
      hematuria and 43 pyuria without cancer. The urinary miR-6124 to miR-4511 ratio
      was considerably higher in BC than in hematuria or pyuria, and enabled the
      discrimination of BC from patients with hematuria at a sensitivity of >90% (p <
      0.001). Conclusively, the proposed noninvasive diagnostic tool based on the
      expression ratio of urinary cell-free miR-6124 to miR-4511 can reduce unnecessary
      cystoscopies in patients with hematuria undergoing evaluation for BC, with a
      minimal loss in sensitivity for detecting cancer.

PMID- 30183089
TI  - Estrogen metabolism in menopausal hormone users in the women's health initiative
      observational study: Does it differ between estrogen plus progestin and estrogen
      alone?
AB  - The WHI found an unexpected reduced breast cancer risk in women using CEE alone.
      We hypothesized CEE alone induces estrogen hydroxylation along the 2-pathway
      rather than the competing 16-pathway, a pattern linked to reduced postmenopausal
      breast cancer risk. One thousand eight hundred and sixty-four women in a WHIOS
      case-control study of estrogen metabolism and ovarian and endometrial cancer were
      studied of whom 609 were current E + P users (351 used CEE + MPA), while 272 used
      E alone (162 used CEE). Fifteen EM were measured, and analyses were conducted for
      each metabolite, hydroxylation pathway (2-, 4-, or 16-pathway) and ratios of
      pathway concentrations using inverse probability weighted linear regression.
      Compared to E + P users, all EM were higher in E alone users (significant for
      unconjugated estrone, total/conjugated estradiol, total/unconjugated 2
      methoxyestrone, 4-methoxyestrone and unconjugated estriol). The relative
      concentrations of 2- and 4-pathway EM did not differ between the MHT users (2
      pathway EM comprised 15% and 4-pathway EM <2% of the total), but 16-pathway EM
      were lower in E alone users (p = 0.036). Ratios of 2- and 4-pathway EM compared
      to 16-pathway EM were significantly higher in E alone compared to E + P users.
      Similar but not significant patterns were observed in CEE-alone and CEE + MPA
      users. Our data suggest that compared to E + P users, women using E alone have
      more extensive metabolism via the 2- vs. the competing 16-pathway. This is
      consistent with epidemiologic evidence of reduced postmenopausal breast cancer
      risk associated with this metabolic profile and may provide a clue to the breast
      cancer risk reduction in CEE alone users during the WHI.

PMID- 30183090
TI  - Solar Ultraviolet Radiation Exposure and Sun Protection Behaviors and Knowledge
      Among a High-Risk and Overlooked Group of Outdoor Workers in South Africa.
AB  - The exposure of outdoor car guards to solar ultraviolet radiation (UVR), the
      majority with deeply pigmented skin, to solar UVR was measured for five
      consecutive days during early spring (September 2017) in South Africa using
      electronic UVR dosimeters attached to the upper arm of each participant. The
      exposure of the nape of the neck, forehead, nose, cheek and hand was extrapolated
      from the measurements. The onsite ambient solar UVR on a flat, horizontal,
      unshaded surface was measured concurrently. The sun-related knowledge, behavior
      and attitudes of the car guards were evaluated using questionnaires. Total
      personal daily solar UVR exposure as a percentage of the ambient solar UVR
      exposure was 24%. The exposure of car guards on several body sites was in excess
      of the occupational threshold limit value. Sleeved shirts and hats were the most
      commonly used sun protection measures (worn by 70% and 80%, respectively).
      Considering the high levels of solar UVR reported on most days throughout the
      year in South Africa, more studies quantifying the personal exposure of outdoor
      workers in both the informal and formal sectors are necessary.

PMID- 30183091
TI  - Real-world benefits of allergen immunotherapy for birch pollen-associated
      allergic rhinitis and asthma.
AB  - BACKGROUND: Real-world evidence is sparse on the benefits of allergen
      immunotherapy [AIT; subcutaneous/sublingual immunotherapy (SCIT/SLIT)], the only
      disease-modifying intervention for allergic rhinitis (AR) with long-term
      efficacy. This real-life study evaluated the effect of six AITs (native pollen
      SLIT/SCIT, four allergoid SCITs) vs symptomatic medication use, on AR symptoms
      and asthma symptoms/onset, in patients with birch pollen-associated AR and/or
      asthma. METHODS: In this retrospective cohort analysis of a German longitudinal
      prescription database, AIT patients received >=2 successive seasonal treatment
      cycles; non-AIT patients had >=3 AR prescriptions in three seasons or previous
      month. Patients were matched for: index year, age, gender, main indication at
      index, number of seasonal cycles within treatment period, baseline AR/asthma
      treatment prescriptions. Multiple regression analysis compared prescription data
      in AIT and non-AIT groups as proxy for clinical status/disease progression.
      RESULTS: Up to 6 years of follow-up, significantly more AIT (65.4%) vs non-AIT
      (47.4%) patients were AR medication-free; odds ratio (OR) [95% confidence
      interval (CI)]: 0.51 [(0.48-0.54); P < 0.001] (28.6% covariate-adjusted reduction
      vs non-AIT; P < 0.001), and significantly more AIT (49.1%) vs non-AIT (35.1%)
      patients were asthma medication-free [OR (95% CI): 0.59 (0.55-0.65); P < 0.001]
      (32% reduction vs non-AIT; P < 0.001), or reduced existing asthma medication use
      (32% covariate-adjusted reduction vs non-AIT; P < 0.001). During treatment, new
      onset asthma risk was significantly reduced in the AIT vs non-AIT group (OR:
      0.83; P = 0.001). CONCLUSIONS: Birch pollen AIT demonstrated real-world benefits
      up to 6 years post-treatment cessation through significantly reduced AR and
      asthma medication intake, and significantly decreased risk of new-onset asthma
      medication use on-treatment.

PMID- 30183092
TI  - Profile of the skin microbiota in a healthy Chinese population.
AB  - The skin microbiota is an inseparable component of the skin barrier structure,
      which participates in the stabilization or impairment of the barrier function as
      well as the development of many skin diseases. To characterize the normal skin
      microbiota and its association with skin sites, age and sex, we recruited 50
      volunteers divided into children, adolescents, young adults, middle-aged adults
      and the elderly. The skin sites consisted of cheeks, volar forearms (representing
      dry environments) and upper back (representing sebaceous environments). A total
      of 9 574 365 high-quality sequences of the V3 to V4 region of the 16S rRNA gene
      were annotated with taxonomic information related to two archaeal phyla
      (Thaumarchaeota and Euryarchaeota) and five dominant bacterial phyla
      (Actinobacteria, Proteobacteria, Firmicutes, Bacteroidetes and Cyanobacteria).
      The skin bacteria community structure was influenced by skin sites, and was
      closely related to age and sex. The upper back was dominated by Propionibacterium
      and Staphylococcus, and the cheeks facilitated the survival of
      Betaproteobacteria, while Alphaproteobacteria were prevalent on the volar
      forearms. Regarding the effects of age, after sexual maturity, the cheek
      microbiota became more similar to sebaceous sites (i.e. the upper back). The
      volar forearms appeared to experience the aging process earlier than the other
      two sites. The elderly had greater species richness and diversity and their
      community composition no longer had skin-site selectivity. Males had a greater
      species richness than females, but the sex differences in the community structure
      only present at certain age groups and skin sites.

PMID- 30183093
TI  - Numerical and experimental investigation of 'water fan' effect due to
      electrohydrodynamic force in a microchamber.
AB  - Electrohydrodynamics is commonly used in microfluidics to control and manipulate
      the fluid. Though there are studies on the rotation flow in suspended films, the
      thin film liquid is easily broken and cannot last long hence not applicable in
      specific applications. Here, we established a three-dimensional microchamber
      embedded with two pairs of microelectrodes to investigate the rotational
      phenomenon of bulk of liquid which we called 'water fan' effect based on the
      electrohydrodynamics force. When proper voltages were applied on these
      microelectrodes, the tornado-like rotation would be generated. Both the numerical
      and experimental results showed that the controllable and continuous rotation
      could be achieved in the microchamber. In addition, the concentration effect
      resulting from the rotation flow was also observed. The proposed method offers
      great promises in providing theoretical and practical guideline in microfluidic
      devices for mixing, separating, and cooling applications.

PMID- 30183094
TI  - Simultaneous high-resolution cardiac T1 mapping and cine imaging using model
      based iterative image reconstruction.
AB  - PURPOSE: To provide high-resolution cardiac T1 mapping of various cardiac phases
      and cine imaging within a single breath-hold using continuous golden ratio-based
      radial acquisition and model-based iterative image reconstruction. METHODS: Data
      acquisition was performed continuously using golden ratio-based radial sampling
      and multiple inversion pulses were applied independent of the heart rate. Native
      T1 maps of diastole and systole were reconstructed with in-plane resolution of
      1.3 * 1.3 mm2 using model-based iterative image reconstruction. Cine images with
      30 cardiac phases were reconstructed from the same data using kt-SENSE. The
      method was evaluated in a commercially available T1 phantom and 10 healthy
      subjects. In vivo T1 assessment was carried out segment-wise. RESULTS: Evaluation
      in the phantom demonstrated accurate T1 times (R2 > 0.99) and insensitivity to
      the heart rate. In vivo T1 values did not differ between systole and diastole,
      and T1 times assessed by the proposed approach were longer than measured with a
      modified Look-Locker inversion recovery (MOLLI) sequence, except for lateral
      segments. Cine images had a consistent dark-blood contrast and functional
      assessment was in agreement with assessment based on Cartesian cine scans
      (difference in ejection fraction: 0.26 +/- 2.65%, P = 0.65). CONCLUSION: The
      proposed approach provides native T1 maps of diastole and systole with high
      spatial resolution and cine images simultaneously within 16 s, which could
      strongly improve the scan efficiency.

PMID- 30183095
TI  - Hazard assessment of the veterinary pharmaceuticals monensin and nicarbazin using
      a soil test battery.
AB  - Veterinary pharmaceuticals are widely used as food additives in the poultry
      industry, and the unknown consequences of releasing these compounds into the
      environment are of concern. The purpose of the present study was to determine the
      direct impact of 2 veterinary pharmaceuticals (nicarbazin and monensin), commonly
      used in the poultry industry, on nontarget invertebrates and plant species.
      Ecotoxicological tests were used to evaluate the acute and chronic toxicity in
      earthworms (Eisenia andrei), collembolans (Folsomia candida), and 2 plant species
      (Brassica rapa and Triticum aestivum). Chemical analytical measurements were in
      good agreement with the nominal concentrations used, although some variability
      was seen. The results obtained showed no effects of nicarbazin at the highest
      nominal tested concentration of 1000 mg a.i./kg soil dry weight on any of the
      organisms, whereas exposure to monensin caused a concentration-specific response
      pattern. Species sensitivity to monensin decreased in the following rank order:
      B. rapa > T. aestivum > E. andrei > F. candida, with measured median effect
      concentrations (based on soil exposure) ranging between approximately 10 and 120
      mg/kg. Our results emphasize the importance of using a test battery when
      assessing ecotoxicological effects by using different ecophysiological endpoints
      and species from different trophic levels. Environ Toxicol Chem 2018;37:3145
      3153. (c) 2018 SETAC.

PMID- 30183096
TI  - Is an artificial pancreas (closed-loop system) for Type 1 diabetes effective?
AB  - The artificial pancreas is now a viable treatment option for people with Type 1
      diabetes and has demonstrated improved glycaemic outcomes while also reducing the
      onus of self-management of Type 1 diabetes. Closed-loop glucose-responsive
      insulin delivery guided by real-time sensor glucose readings can accommodate
      highly variable day-to-day insulin requirements and reduce the hypoglycaemia risk
      observed with tight glycaemic control in Type 1 diabetes. In 2011, the James Lind
      Alliance research priorities for Type 1 diabetes were produced and priority 3 was
      to establish whether an artificial pancreas (closed-loop system) for Type 1
      diabetes is effective. This review focuses on the progress that has been made in
      the evolution of closed-loop systems as an effective treatment option for Type 1
      diabetes. Development of closed-loop systems has advanced from feasibility
      evaluations in highly supervised settings over short periods, to clinical studies
      in free-living, unsupervised conditions lasting several months. The approval in
      the USA of the first hybrid closed-loop system (MiniMed(r) 670G pump, Medtronic,
      Northridge, CA, USA) in 2016 for use in Type 1 diabetes reflects these
      advancements. We discuss the evidence from clinical studies that closed-loop
      systems are effective with improved glycaemic outcomes, reduced hypoglycaemia and
      had positive end-user acceptance in children, adolescents, adults and pregnant
      women with Type 1 diabetes. We also present the outlook for future closed-loop
      systems in the treatment of Type 1 diabetes and identify the challenges facing
      the wide-spread clinical adoption of this technology.

PMID- 30183097
TI  - Morphometric characteristics and time to hatch as efficacious indicators for
      potential nanotoxicity assay in zebrafish.
AB  - Although the effects of nano-sized titania (nTiO2 ) on hatching events (change in
      hatching time and total hatching) in zebrafish have been reported, additional
      consequences of nTiO2 exposure (i.e., the effects of nTiO2 -induced changes in
      hatching events and morphometric parameters on embryo-larvae development and
      survivability) have not been reported. To address this knowledge gap, embryos 4 h
      postfertilization were exposed to nTiO2 (0, 0.01, 10, and 1000 MUg/mL) for 220 h.
      Hatching rate (58, 82, and 106 h postexposure [hpe]), survival rate (8 times from
      34 to 202 hpe), and 21 morphometric characteristics (8 times from 34 to 202 hpe)
      were recorded. Total hatching (rate at 106 hpe) was significantly and positively
      correlated to survival rate, but there was no direct association between nTiO2 
      induced change in hatching time (hatching rate at 58 and 82 hpe) and survival
      rate. At 58, 82, and 106 hpe, morphometric characteristics were significantly
      correlated to hatching rate, suggesting that the nTiO2 -induced change in
      hatching time can affect larval development. The morphometric characteristics
      that were associated with change in hatching time were also significantly
      correlated to survival rate, suggesting an indirect significant influence of the
      nTiO2 -induced change in hatching time on survivability. These results show a
      significant influence of nTiO2 -induced change in hatching events on zebrafish
      embryo-larvae development and survivability. They also show that morphometric
      maldevelopments can predict later-in-life consequences (survivability) of an
      embryonic exposure to nTiO2 . This suggests that zebrafish can be sensitive
      biological predictors of nTiO2 acute toxicity. Environ Toxicol Chem 2018;37:3063
      3076. (c) 2018 SETAC.

PMID- 30183098
TI  - Quantification of solute diffusivity in osteoarthritic human femoral cartilage
      using correlation spectroscopy.
AB  - Osteoarthritis is a chronic joint disease characterized by articular cartilage
      degeneration, pain, and disability. As an avascular tissue, the movement of water
      and solutes through the tissue is critical to cartilage health and function, and
      early changes in solute diffusivity due to micro-scale changes in the properties
      of cartilage's extracellular matrix might precede clinical symptoms. A diagnostic
      technique for quantifying alteration to the diffusive environment of cartilage
      that precedes macroscopic changes may allow for the earlier identification of
      osteoarthritic disease, facilitating earlier intervention strategies. Toward this
      end, we used two confocal microscopy-based correlation spectroscopy techniques,
      fluorescence correlation spectroscopy and raster image correlation spectroscopy,
      to quantify the diffusion of two small solutes, fluorescein and 3k dextran,
      within human osteoarthritic articular cartilage. Our goal was to determine if
      these relatively simple optical correlation spectroscopy techniques could detect
      changes in solute diffusivity associated with increasing cartilage damage as
      assessed by International Cartilage Repair Society scoring guidelines, and if
      these measures are correlated with mechanical and compositional measures of
      cartilage health. Our data show a modest, yet significant increase in solute
      diffusivity and cartilage permeability with increasing osteoarthritis score
      (grades 0-2), with a strong correlation between diffusion coefficients,
      permeability, and cartilage composition. The described correlation spectroscopy
      techniques are quick, simple, and easily adapted to existing laboratory workflow
      and equipment. Furthermore, the minimal solute concentrations and laser powers
      required for analysis, combined with recent advances in arthroscopic microscopy,
      suggest correlation spectroscopy techniques as translational candidates for
      development into early OA diagnosis tools. (c) 2018 Orthopaedic Research Society.
      Published by Wiley Periodicals, Inc. J Orthop Res.

PMID- 30183099
TI  - Industrial and natural compounds in filter-feeding black fly larvae and water in
      3 tundra streams.
AB  - We report concentrations of polychlorinated biphenyls, polybrominated diphenyl
      ethers, novel flame retardants, and naturally occurring bromoanisoles in water
      and filter-feeding black fly (Simuliidae) larvae in 3 tundra streams in northern
      Sweden. The results demonstrate that black fly larvae accumulate a wide range of
      organic contaminants and can be used as bioindicators of water pollution in
      Arctic streams. Environ Toxicol Chem 2018;37:3011-3017. (c) 2018 SETAC.

PMID- 30183100
TI  - Inpatient hypoglycaemia; should we should we focus on the guidelines, the targets
      or our tools?
AB  - In their thought-provoking commentary, Levy et al. [1] explore the possible
      unintended consequences of United Kingdom (UK) guideline targets on the high
      frequency of hypoglycaemia in people with diabetes who are hospitalized. The
      authors cite the National Institute for Health and Care Excellence (NICE) and the
      Joint British Diabetes Societies (JBDS) guidelines pertaining to inpatient,
      surgical and pregnancy diabetes care. These guidelines suggest using lower limits
      of glucose targets varying from 4.0 to 6.0 mmol/l [2-4]. Levy et al. propose a
      lower glucose limit of 5 mmol/l with the catchphrase 'stop at 5 and keep the
      inpatient alive'. This article is protected by copyright. All rights reserved.

PMID- 30183101
TI  - Nomenclature for real-time magnetic resonance imaging.

PMID- 30183102
TI  - Alirocumab safety in people with and without diabetes mellitus: pooled data from
      14 ODYSSEY trials.
AB  - AIM: To evaluate the safety of the proprotein convertase subtilisin/kexin type 9
      (PCSK9) inhibitor alirocumab according to diabetes mellitus status. METHODS:
      Safety data from 14 trials (8-104-week durations) were analysed by treatment
      (alirocumab or placebo/ezetimibe control) and diabetes status (yes/no, defined by
      medical history). Adverse event data were assessed using descriptive statistics
      and Cox models. RESULTS: Of the 5234 trial participants, 1554 (29.7%) had
      diabetes. Overall, treatment-emergent adverse events were similar in the
      alirocumab and control groups, except for more frequent local injection site
      reactions with alirocumab. Fewer people with diabetes experienced local injection
      site reactions [alirocumab, 3.5%, control, 2.9%; hazard ratio 1.24 (95% CI 0.68
      2.25)] than those without diabetes [alirocumab, 7.5%; control, 4.9%; hazard ratio
      1.51 (95% CI 1.13-2.01)]. Those with diabetes reported a greater number of
      serious adverse events (alirocumab, 19.4%; control, 19.7%) than those without
      diabetes (alirocumab, 14.5%; control, 13.5%). In people with diabetes, major
      adverse cardiac events occurred in 2.7% of alirocumab-treated people [control,
      3.3%; hazard ratio 0.74 (95% CI 0.41-1.35)]; in those without diabetes, 1.8% of
      alirocumab-treated people had major adverse cardiac events [control, 1.7%; hazard
      ratio 0.95 (95% CI 0.56-1.62)]. Overall, no increase in HbA1c or fasting plasma
      glucose vs control treatment groups was observed, regardless of diabetes status.
      CONCLUSION: This pooled analysis across 14 trials demonstrated similar safety for
      alirocumab vs control treatment, irrespective of diabetes status, except for more
      frequent local injection site reactions with alirocumab. People with diabetes
      reported fewer local injection site reactions than those without diabetes.

PMID- 30183103
TI  - Molecular and structural bases of interaction between extracellular domains of
      nectin-2 and N-cadherin.
AB  - Cell adhesion molecules such as nectins and cadherins play important role in the
      formation of adherens junction. While nectins interact through their
      extracellular domains in both homophilic and heterophilic manner among
      themselves, extracellular domains of cadherins participate only in homophilic
      fashion to mediate cell-cell adhesion. It is well established that nectins
      recruit cadherins in the adhesion sites through an interplay of adaptor molecules
      in the cytoplasmic side thereby increasing the effective concentration of both
      the adhesion molecules on the cell surface. This study provides molecular and
      structural bases of the novel interaction between extracellular domains of nectin
      2 and N-cadherin, by which nectins can also recruit cadherins at the site of
      adherens junction through an adaptor-independent mechanism. Surface plasmon
      resonance study demonstrates that nectin-2 can directly recognize N-cadherin with
      a KD of 3.5 +/- 0.6 MUM which is physiologically relevant considering the
      affinities between other cell adhesion molecules including cadherin dimerization.
      Furthermore, structural analysis of currently available homodimeric structures of
      both nectin-2 and N-cadherin followed by molecular docking as well as
      complementary mutagenesis studies revealed the binding interface of this novel
      interaction.

PMID- 30183104
TI  - National guidelines have contributed to safer care for inpatients with diabetes.
AB  - The Commentary by Levy et al. [1] argues that the high incidence of inpatient
      hypoglycaemia in the recent National Diabetes Inpatient Audit (NaDIA) is not
      simply down to 'errors' by clinicians, but also to 'system defects in national
      guidance'. We agree that inpatient hypoglycaemia and the wider issue of inpatient
      safety are extremely important, and recognize the importance of the unique
      anaesthetic perspective. This article is protected by copyright. All rights
      reserved.

PMID- 30183105
TI  - Hydrolysis of oligosaccharides by a fungal alpha-galactosidase from fruiting
      bodies of a wild mushroom Leucopaxillus tricolor.
AB  - A novel acidic alpha-galactosidase (EC 3.2.1.22) designated as Leucopaxillus
      tricolor alpha-galactosidase (LTG) has been purified to homogeneity from the
      fruiting bodies of L. tricolor to 855-fold with a specific activity of 956 U mg-1
      by the application of chromatography and gel filtration. The molecular mass of
      LTG was estimated to be 60 kDa as determined by both SDS-PAGE and by gel
      filtration. The purified enzyme was identified by LC-MS/MS and four inner amino
      acid sequences were obtained. When 4-nitrophenyl alpha-D-glucopyranoside (pNPGal)
      was used as substrate, the optimal pH and optimal temperature of LTG were pH 5.0
      and 50  degrees C, respectively. The enzyme activity was strongly inhibited by
      Hg2+ , Fe3 , Cu2+ , Cd2+ , and Mn2+ ions. The chemical modification agent N
      bromosuccinimide (NBS) completely inhibited the enzyme activity of LTG,
      indicating the paramount importance of tryptophan residue(s) to its enzymatic
      activity. Besides, LTG displayed wide substrate diversity with activity toward a
      variety of substrates such as stachyose, raffinose, melibiose, locust bean gum,
      and guar gum. Given the good ability of degrading the non-digestible and
      flatulence-causing oligosaccharides, this fungus may become a useful source of
      alpha-galactosidase for multiple applications.

PMID- 30183106
TI  - Exopolysaccharides producing rhizobacteria and their role in plant growth and
      drought tolerance.
AB  - Drought stress not only effect the population and activities of microorganisms
      inhabiting the rhizosphere but also various physiological and biochemical process
      in plants that is, photosynthesis, respiration, translocation, uptake of ions,
      carbohydrates, and nutrient metabolism. Plant growth promoting rhizobacteria
      (PGPR) and their exopolysaccharides (EPS) showed profound effects on plant growth
      and drought tolerance. Reactions of bacteria to drought stress at various
      organizational levels are different which depends on intensity of stress,
      duration, species, and growth stage. PGPR could be effectively utilized in
      developing strategies to facilitate water conservation strategies of plants. They
      have the ability to improve plant growth directly by enhancing level of
      phytohormones, siderophore, biofilm, and exopolysaccharides production and by
      increasing the nutrient availability in the rhizosphere or indirectly by
      protecting plants from pathogen attack. EPS producing bacteria are capable to
      maintain higher soil moisture content and growth of plants even under severe
      dried sandy soils. The evidence of survival of rhizobacteria under low moisture
      content obtained from the fact of rhizobacterial occurrence in the soil of desert
      and effective nodule formation in desert soil. Beside this, EPS produced by PGPR
      form rhizosheath around the roots and thus protect the plant roots from
      desiccation for a longer period of time. Important role exhibited by
      exopolysaccharides includes, protection from desiccation, microbial aggregation,
      plant-microbe interaction, surface attachment, bioremediation and its use by many
      industries for stabilizing, thickening, coagulating, gelling, suspending and for
      film forming. Plants inoculated with EPS-producing bacteria showed higher
      accumulation of proline, sugars, and free amino acids under water deficit stress.
      Biofilms formed by the PGPR around the roots are made up of bacterial populations
      or bacterial communities that encased inside the polymeric extracellular matrix
      formed by bacteria itself, they adhered to the external surfaces that contain
      sufficient moisture. It is concluded that the application of PGPR in combination
      with their EPS is a promising measure to combat drought stress thus, increasing
      global food security.

PMID- 30183107
TI  - Dynamical comparison between myoglobin and hemoglobin.
AB  - Myoglobin and hemoglobin are globular hemeproteins, when the former is a monomer
      and the latter a heterotetramer. Despite the structural similarity of myoglobin
      to alpha and beta subunits of hemoglobin, there is a functional difference
      between the two proteins, owing to the quaternary structure of hemoglobin. The
      effect of the quaternary structure of hemoglobin on the intrinsic dynamics of its
      subunits is explored by dynamical comparison of the two proteins. Anisotropic
      Network Model modes of motion were calculated for hemoglobin and myoglobin.
      Dynamical comparison between the proteins was performed using global and local
      Anisotropic Network Model mode alignment algorithms based on the algorithms of
      Smith-Waterman and Needleman-Wunsch for sequence comparison. The results indicate
      that the quaternary structure of hemoglobin substantially alters the intrinsic
      dynamics of its subunits, an effect that may contribute to the functional
      difference between the two proteins. Local dynamics similarity between the
      proteins is still observed at the major exit route of the ligand.

PMID- 30183108
TI  - Gradient-echo and spin-echo blood oxygenation level-dependent functional MRI at
      ultrahigh fields of 9.4 and 15.2 Tesla.
AB  - PURPOSE: Sensitivity and specificity of blood oxygenation level-dependent (BOLD)
      functional MRI (fMRI) is sensitive to magnetic field strength and acquisition
      methods. We have investigated gradient-echo (GE)- and spin-echo (SE)-BOLD fMRI at
      ultrahigh fields of 9.4 and 15.2  Tesla. METHODS: BOLD fMRI experiments
      responding to forepaw stimulation were performed with 3 echo times (TE) at each
      echo type and B0 in alpha-chloralose-anesthetized rats. The contralateral
      forelimb somatosensory region was selected for quantitative analyses. RESULTS: At
      9.4 T and 15.2 T, average baseline T2 * (n = 9) was 26.6 and 17.1 msec, whereas
      baseline T2 value (n = 9) was 35.7 and 24.5 msec, respectively. Averaged
      stimulation-induced DeltaR2 * was -1.72 s-1 at 9.4 T and -3.09 s-1 at 15.2 T,
      whereas DeltaR2 was -1.19 s-1 at 9.4 T and -1.97 s-1 at 15.2 T. At the optimal TE
      of tissue T2 * or T2 , BOLD percent changes were slightly higher at 15.2 T than
      at 9.4 T (GE: 7.4% versus 6.4% and SE: 5.7% versus 5.4%). The DeltaR2 * and
      DeltaR2 ratio of 15.2 T to 9.4 T was 1.8 and 1.66, respectively. The ratio of the
      macrovessel-containing superficial to microvessel-dominant parenchymal BOLD
      signal was 1.73 to 1.76 for GE-BOLD versus 1.13 to 1.19 for SE-BOLD, indicating
      that the SE-BOLD contrast is less sensitive to macrovessels than GE-BOLD.
      CONCLUSION: SE-BOLD fMRI improves spatial specificity to microvessels compared to
      GE-BOLD at both fields. BOLD sensitivity is similar at the both fields and can be
      improved at ultrahigh fields only for thermal-noise-dominant ultrahigh-resolution
      fMRI.

PMID- 30183109
TI  - Comparative study of the effect of disease causing and benign mutations in
      position Q92 on cholesterol binding by the NPC1 n-terminal domain.
AB  - The Niemann-Pick type C1 (NPC1) protein is a large transmembrane protein located
      in lysosomes/endosomes. NPC1 binds cholesterol (CLR) and transports it to
      cellular membrane and endoplasmic reticulum. Mutations in NPC1 cause Niemann-Pick
      type C (NPC) disease, a rare autosomal disorder characterized by intracellular
      accumulations of CLR and subsequent neurodegeneration leading to premature death.
      Among known disease-causing mutations in NPC1, Q92R is the one that is located in
      the N-terminal cholesterol-binding domain [NTD]. Here we study the effect of the
      mutation on the ability of NPC1 (NTD) to bind and retain CLR in the binding
      pocket using structural analysis. We compare characteristics of the Q92R and Q92S
      mutant type (MT) protein, which is predicted to be benign. We provide detailed
      investigation of the CLR-NPC1 (NTD) binding process; and propose the mechanism,
      by which Q92R mutation causes NPC disease. We show that although Q92 residue
      neither directly participates in catalytic activity of the NPC1 (NTD), nor
      defines its CLR-binding specificity - it is important for the overall protein
      structure as well as for providing favorable electrostatic environment for CLR
      transfer. Our results suggest that a negative electrostatic potential of the CLR
      binding site (the S-opening) might promote NPC2 interaction with NPC1 (NTD)
      and/or proper CLR orientation and its enforced transfer. We show that in contrast
      to the benign Q92S mutation, Q92R significantly reduces electrostatic potential
      around S-opening, and thus likely affects NPC1 (NTD)-NPC2 interaction and/or CLR
      transfer from NPC2 to NPC1.

PMID- 30183110
TI  - Structural and biochemical characterization of Plasmodium falciparum Hsp70-x
      reveals functional versatility of its C-terminal EEVN motif.
AB  - Plasmodium falciparum, the main agent of malaria expresses six members of the
      heat shock protein 70 (Hsp70) family. Hsp70s serve as protein folding
      facilitators in the cell. Amongst the six Hsp70 species that P. falciparum
      expresses, Hsp70-x (PfHsp70-x), is partially exported to the host red blood cell
      where it is implicated in host cell remodeling. Nearly 500 proteins of parasitic
      origin are exported to the parasite-infected red blood cell (RBC) along with
      PfHsp70-x. The role of PfHsp70-x in the infected human RBC remains largely
      unclear. One of the defining features of PfHsp70-x is the presence of EEVN
      residues at its C-terminus. In this regard, PfHsp70-x resembles canonical
      eukaryotic cytosol-localized Hsp70s which possess EEVD residues at their C
      termini in place of the EEVN residues associated with PfHsp70-x. The EEVD
      residues of eukaryotic Hsp70s facilitate their interaction with co-chaperones.
      Characterization of the role of the EEVN residues of PfHsp70-x could provide
      insights into the function of this protein. In the current study, we expressed
      and purified recombinant PfHsp70-x (full length) and its EEVN minus form (PfHsp70
      xT ). We then conducted structure- function assays towards establishing the role
      of the EEVN motif of PfHsp70-x. Our findings suggest that the EEVN residues of
      PfHsp70-x are important for its ATPase activity and chaperone function.
      Furthermore, the EEVN residues are crucial for the direct interaction between
      PfHsp70-x and human Hsp70-Hsp90 organizing protein (hHop) in vitro. Hop
      facilitates functional cooperation between Hsp70 and Hsp90. However, it remains
      to be established if PfHsp70-x and hHsp90 cooperate in vivo.

PMID- 30183111
TI  - Recent Progress on Cyclic Nitrenoid Precursors in Transition-metal-catalyzed
      Nitrene-transfer Reactions.
AB  - Nitrene-transfer reactions have been a powerful synthetic method for direct
      incorporation of nitrogen atoms into organic molecules. Discovery of novel
      nitrene-transfer reactions has been dominantly supported by not only the
      improvement in transition-metal catalysts but also by the employment of novel
      precursors of nitrenoids. Since the pioneering works utilizing organic azides or
      iminoiodinanes as practical synthetic tools for nitrogen-containing compounds
      were reported, a new approach using various N-heterocycles containing strain
      energy or a weak bond has emerged. In this review, we briefly summarize the
      history of nitrene-transfer chemistry from the viewpoint of its precursors. In
      particular, the use of N-heterocycles such as 2H-azirines, 1,4,2-dioxazol-5-ones,
      1,2,4-oxadiazol-5-ones, isoxazol-5(4H)-ones, and isoxazoles are comprehensively
      described, showing the recent remarkable progress in this chemistry.

PMID- 30183112
TI  - Iron- or Palladium-Catalyzed Reaction Cascades Merging Cycloisomerization and
      Cross-Coupling Chemistry.
AB  - A conceptually novel reaction cascade is presented, which allows readily
      available enynes to be converted into functionalized 1,3-dienes comprising a
      stereodefined tetrasubstituted alkene unit; such compounds are difficult to make
      by conventional means. The overall transformation is thought to commence with
      formation of a metallacyclic intermediate that evolves via cleavage of an
      unstrained C-X bond in its backbone. This non-canonical cycloisomerization
      process is followed by a cross-coupling step, such that reductive C-C bond
      formation regenerates the necessary low-valent metal fragment and hence closes an
      intricate catalytic cycle. The cascade entails the formation of two new C-C bonds
      at the expense of the constitutional C-X entity of the substrate: importantly,
      the extruded group X must not be a heteroelement (X=O, NR), since activated beta
      C-C bonds can also be broken. This concern was reduced to practice in two largely
      complementary formats: one procedure relies on the use of alkyl-Grignard reagents
      in combination with catalytic amounts of Fe(acac)3, whereas the second method
      amalgamates cycloisomerization with Suzuki coupling by recourse to arylboronic
      acids and phosphine-ligated palladium catalysts.

PMID- 30183113
TI  - Postoperative patient handovers-Variability in perceptions of quality: A
      qualitative focus group study.
AB  - AIMS AND OBJECTIVES: (a) To explore the factors affecting quality in
      postoperative handovers as perceived by the different professional groups of
      clinicians involved. (b) To explore possible differences in perceptions of
      postoperative handover quality across professional groups and level of
      experience. BACKGROUND: High quality patient handovers after surgery and
      anaesthesia are important to ensure patient safety. There is a paucity of
      research describing contextual factors related to handover quality and the
      perspectives of different professional groups involved. DESIGN: A qualitative
      exploratory design was applied. METHOD: A total of eight focus group interviews
      with 37 participants (29 nurses, eight doctors) were conducted.
      Anaesthesiologists, resident anaesthesiologists, nurse anaesthetists,
      postoperative care nurses and operating room nurses participated in the study.
      The interviews were conducted according to profession with two groups per
      profession: one with experienced clinicians and one with less experienced
      clinicians. The data were analysed using thematic analysis. The study adheres to
      the COREQ guidelines. RESULTS: The data analysis identified the following factors
      affecting postoperative handover quality: "timing and concurrency conflicts,"
      "handover structure," "patient conditions," "individual characteristics of
      clinicians involved" and "team composition." Differences across professional
      groups and level of experience were related to responsibility, structure and
      adaptation. CONCLUSION: The professional groups involved describe the
      postoperative patient handover as a complex and variable process that needs to be
      carefully planned and executed according to the influencing factors. Variability
      exists across professional groups and level of experience. RELEVANCE TO CLINICAL
      PRACTICE: Health care providers need to be aware that postoperative handovers are
      affected by a set of factors related to internal (patient conditions, individual
      characteristics of clinicians involved and team composition) and external (timing
      and concurrency conflicts, handover structure) characteristics. These issues need
      to be acknowledged when procedures and routines for handover quality are
      designed, implemented and used.

PMID- 30183114
TI  - Polycrystalline and Single-Crystal Cu Electrodes: Influence of Experimental
      Conditions on the Electrochemical Properties in Alkaline Media.
AB  - Single and polycrystalline Cu electrodes serve as model systems for the study of
      the electroreduction of CO2 , CO and nitrate, or for corrosion studies; even so,
      there are very few reports combining electrochemical measurements with structural
      characterization. Herein both the electrochemical properties of polycrystalline
      Cu and single crystal Cu(1 0 0) electrodes in alkaline solutions (0.1 m KOH and
      0.1 m NaOH) are investigated. It is demonstrated that the pre-treatment of the
      electrodes plays a crucial role in determining their electrochemical properties.
      Scanning tunneling microscopy, X-ray photoelectron spectroscopy and cyclic
      voltammetry are performed on Cu(1 0 0) electrodes prepared under UHV conditions;
      it is shown that the electrochemical properties of these atomically well-defined
      electrodes are distinct from electrodes prepared by other methods. Also
      highlighted is the significant role of residual oxygen and electrolyte convection
      in influencing the electrochemical properties.

PMID- 30183115
TI  - Driving pressure and acute respiratory distress syndrome in critically ill
      patients.
AB  - BACKGROUND AND OBJECTIVE: Elevated driving pressure (DeltaP) may be associated
      with increased risk of acute respiratory distress syndrome (ARDS) in patients
      admitted via the emergency department and with post-operative pulmonary
      complications in surgical patients. This study investigated the association of
      higher DeltaP with the onset of ARDS in a high-risk, intensive care unit (ICU)
      population. METHODS: This is a secondary analysis of a prospective multicentre
      observational study. Data for this ancillary study were obtained from intubated
      adult patients with at least one ARDS risk factor upon ICU admission enrolled in
      a previous multicentre observational study. Patients were followed up for the
      development of ARDS within 7 days (primary outcome). Univariate and multivariate
      analyses tested the association between DeltaP (measured at ICU admission
      (baseline) or 24 h later (day 1)) and the development of ARDS. RESULTS: A total
      of 221 patients were included in this study, among whom 34 (15%) developed ARDS
      within 7 days. These patients had higher baseline DeltaP than those who did not
      (mean +/- SD: 12.5 +/- 3.1 vs 9.8 +/- 3.4 cm H2 O, respectively, P = 0.0001). The
      association between baseline DeltaP and the risk of developing ARDS was robust to
      adjustment for baseline tidal volume, positive-end expiratory pressure, illness
      severity, serum lactate and sepsis, pneumonia, severe trauma and shock as primary
      ARDS risk factors (odds ratio: 1.20; 95% CI: 1.03-1.41; P = 0.02). The same
      results were found with day 1 DeltaP. CONCLUSION: Among at-risk ICU patients,
      higher DeltaP may identify those who are more likely to develop ARDS.

PMID- 30183116
TI  - Ionization methods for the mass spectrometry of organometallic compounds.
AB  - The rapid development of new ionization methods has greatly expanded the ability
      of mass spectrometry to target diverse areas of chemistry. Synthetic
      organometallic and inorganic chemists often find themselves with interesting
      characterization problems that mass spectrometry could potentially find the
      answer for, but without a guide for choosing the appropriate method of analysis.
      This tutorial review seeks to provide that guidance via a simple flow chart
      followed by a brief description of how each common ionization method works. It
      covers all of the commonly used ionization techniques as well as promising
      variants and aims to be a resource of first resort for organometallic chemists
      and analysts tackling a new problem.

PMID- 30183117
TI  - No Heat, No Light-The Future of Sulfur Polymers Prepared at Room Temperature Is
      Bright.
AB  - Follow the yellow brick road: Functional polymers can be prepared directly at
      room temperature from elemental sulfur by the Willgerodt-Kindler reaction. This
      method opens a new synthetic door for the synthesis and application of
      polythioamides and polythioureas.

PMID- 30183118
TI  - Bottom-Up Construction of an Adaptive Enzymatic Reaction Network.
AB  - The reproduction of emergent behaviors in nature using reaction networks is an
      important objective in synthetic biology and systems chemistry. Herein, the first
      experimental realization of an enzymatic reaction network capable of an adaptive
      response is reported. The design is based on the dual activity of trypsin, which
      activates chymotrypsin while at the same time generating a fluorescent output
      from a fluorogenic substrate. Once activated, chymotrypsin counteracts the
      trypsin output by competing for the fluorogenic substrate and producing a non
      fluorescent output. It is demonstrated that this network produces a transient
      fluorescent output under out-of-equilibrium conditions while the input signal
      persists. Importantly, in agreement with mathematical simulations, we show that
      optimization of the pulse-like response is an inherent trade-off between maximum
      amplitude and lowest residual fluorescence.

PMID- 30183119
TI  - Plasmon-Enhanced Solar Water Splitting on Metal-Semiconductor Photocatalysts.
AB  - Photocatalytic water splitting using solar energy has been widely studied as a
      promising method for clean energy production. Continued efforts have been made to
      enhance the performance of solar-to-fuel energy conversion. The introduction of
      localized surface plasmon resonance (SPR) has been proposed as a promising
      strategy to enhance the efficiency of photocatalytic water splitting. This review
      presents an overview of the recent progress in the development of plasmonic
      photocatalysts for solar water splitting. Plasmon-enhanced mechanisms, including
      hot electron injection, near-field effects, and light scattering/trapping, are
      discussed. Furthermore, recent relevant works to discuss the emerging strategies
      for efficiency improvement and better understanding of the mechanisms are
      summarized. Finally, the perspectives of plasmonic photocatalysts for water
      splitting and the possible research directions are presented and discussed.

PMID- 30183120
TI  - Coagulation biomarkers in healthy male Cynomolgus macaque monkeys (Macaca
      fascicularis).
AB  - We designed this study to define reference values of the cynomolgus monkey
      coagulation system, as the normal range of values has not been established.
      Measurement of coagulation function was determined by testing plasma samples from
      30 healthy male cynomolgus monkeys. Prothrombin time (PT), PT activity, PT
      international normalized ratio (INR), activated prothrombin time (aPTT),
      antithrombin III activity, factor II, V, VII, VIII, IX, X, XI, and XII, protein C
      activity, protein S activity, and d-dimer were measured using standardized
      techniques. Mean age and body weight were 69.5 +/- 11.8 months and 5.3 +/- 0.8
      kg, respectively. The mean PT, PT activity, PT INR, aPTT, and antithrombin III
      activities were 11.72 seconds (95% CI = 10.55-12.88), 143.4% (95% CI = 102.0
      184.9), 0.85 (95% CI = 0.74-0.96), 28.2 seconds (95% CI = 23.24-33.09), and 99.7%
      (95% CI = 79.2-120.3), respectively. The mean activities of factors II, V, VII,
      VIII, IX, X, XI, and XII were 110.2% (95% CI = 88.8-131.5), 134.1% (95% CI = 73.0
      195.2), 318.9% (95% CI = 185.0-452.9) 160.2% (95% CI = 96.9-261.3), 38.0% (95% CI
      = 20.9-55.1), 85.7% (95% CI = 61.4-110.0), 155.0% (95% CI = 81.4-228.6), and
      353.7% (95% CI = 246.7-460.6), respectively. The mean activities of protein C and
      protein S were 195.7% (95% CI = 133.4-258.0) and 122.7% (95% CI = 83.2-162.3),
      respectively. The mean level of d-dimer was 1.80 MUg/mL (95% CI = 0.27-3.33).
      Factors V (P = 0.008), IX (P = 0.002), and XI (P = 0.002), and protein S activity
      (P = 0.025) were positively correlated with age. Our study presented the baseline
      values of coagulation biomarkers of cynomolgus monkeys. Despite the similarity to
      previous published studies, more data are required to elucidate the age effect on
      coagulation biomarkers.

PMID- 30183121
TI  - Isolation and expression analysis of cadmium-induced genes from Cd/Mn
      hyperaccumulator Phytolacca americana in response to high Cd exposure.
AB  - Phytolacca americana is recognised as a hyperaccumulator that accumulates cadmium
      (Cd) and manganese (Mn). Although most studies have provided abundant
      physiological evidence, little is known about the molecular mechanisms of Cd
      accumulation in P. americana. In this study, Cd-induced genes were isolated using
      suppression subtractive hybridisation (SSH) library construction, and gene
      expression patterns under Cd stress were quantified using real-time quantitative
      PCR. The functions of PaGST, PaMT and PaFe-SOD were confirmed in transformant
      yeast. Reactive oxygen species (ROS) formation and cell death in root tips were
      detected, and SOD and POD activities in leaf tissue were also analysed. There
      were about 447 expressed sequence tags (ESTs) identified and confirmed. GO
      analysis showed those genes were mainly involved in metabolism, cell stress and
      defence, transcription and translation, signal transduction, transport, energy
      and ion transport, which formed the basis for a molecular understanding of P.
      americana Cd tolerance mechanisms. Cd also stimulated ROS formation and modified
      the antioxidant systems. Taken together, our results indicate that ROS formation
      and Cd-induced gene expression favour P. americana tolerance by activating the
      defence system and permitting subsequent adaptation to Cd toxicity.

PMID- 30183122
TI  - Vaso-occlusive crisis as a predictor of symptomatic avascular necrosis in
      children with sickle cell disease.
AB  - Avascular necrosis (AVN) is a chronic bone complication of sickle cell disease
      (SCD) resulting in significant morbidity. Understanding associated risk factors
      can facilitate risk-based screening, earlier identification, and prompt
      intervention. Between 1998 and 2014, 26 symptomatic cases with imaging evidence
      of AVN were compared 1:5 with age- and SCD genotype-matched controls (n = 128).
      Patients with 1-5 vaso-occlusive crisis (VOC) (OR 11.9, 95% CI, 1.4-99.9; P =
      0.02) and more than 5 VOC (OR 53.6, 95% CI, 5.5-520.2; P = 0.0006) in a 5-year
      period were more likely to have AVN. Symptomatic patients with more than five VOC
      in 5 years may benefit from radiologic screening for AVN.

PMID- 30183123
TI  - A Ma10 gene encoding P-type ATPase is involved in fruit organic acid accumulation
      in apple.
AB  - Acidity is one of the main determinants of fruit organoleptic quality. Here,
      comparative transcriptome analysis was conducted between two cultivars that
      showed a significant difference in fruit acidity, but contained homozygous non
      functional alleles at the major gene Ma1 locus controlling apple fruit acidity. A
      candidate gene for fruit acidity, designated M10, was identified. The M10 gene
      encodes a P-type proton pump, P3A -ATPase, which facilitates malate uptake into
      the vacuole. The Ma10 gene is significantly associated with fruit malate content,
      accounting for ~7.5% of the observed phenotypic variation in apple germplasm.
      Subcellular localization assay showed that the Ma10 is targeted to the tonoplast.
      Overexpression of the Ma10 gene can complement the defect in proton transport of
      the mutant YAK2 yeast strain and enhance the accumulation of malic acid in apple
      callus. Moreover, its ectopic expression in tomato induces a decrease in fruit
      pH. These results suggest that the Ma10 gene has the capacity for proton pumping
      and plays an important role in fruit vacuolar acidification in apple. Our study
      provides useful knowledge towards comprehensive understanding of the complex
      mechanism regulating apple fruit acidity.

PMID- 30183124
TI  - TaCOLD1 defines a new regulator of plant height in bread wheat.
AB  - Plant height is among the most important agronomic traits that influence crop
      yield. However, in addition to the Rht-1 alleles, the molecular basis of plant
      height in bread wheat remains largely unclear. Based on wheat gene expression
      profiling analysis, we identify a light-regulated gene from bread wheat,
      designated as TaCOLD1, whose encoding protein is homologous to cold sensor COLD1
      in rice. We show that TaCOLD1 protein is localized to the endoplasmic reticulum
      (ER) and plasma membrane. Phenotypic analyses show that overexpression of a
      mutated form of TaCOLD1 (M187K) in bread wheat cultivar Kenong199 (Rht-B1b)
      background resulted in an obvious reduction in plant height. Further, we
      demonstrate that the hydrophilic loop of TaCOLD1 (residues 178-296) can interact
      with TaGalpha-7A (the alpha subunit of heterotrimeric G protein) protein but not
      TaGalpha-1B, and the mutation (M187K) in TaCOLD1 remarkably enhances its
      interaction with TaGalpha-7A. Physical interaction analyses show that the C
      terminal region of TaGalpha-7A, which is lacking in the TaGalpha-1B protein, is
      necessary for its interaction with TaCOLD1. Intriguingly, the C-terminal region
      of TaGalpha-7A is also physically associated with the TaDEP1 protein (an atypical
      Ggamma subunit). Significantly, we discover that TaCOLD1 and mTaCOLD1 (M187K) can
      interfere with the physical association between TaGalpha-7A and TaDEP1. Together,
      this study reveals that TaCOLD1 acts as a novel regulator of plant height through
      interfering with the formation of heterotrimeric G protein complex in bread wheat
      and is a valuable target for the engineering of wheat plant architecture.

PMID- 30183125
TI  - Design of a bacterial speck resistant tomato by CRISPR/Cas9-mediated editing of
      SlJAZ2.
AB  - Due to their different lifestyles, effective defence against biotrophic pathogens
      normally leads to increased susceptibility to necrotrophs, and vice versa.
      Solving this trade-off is a major challenge for obtaining broad-spectrum
      resistance in crops and requires uncoupling the antagonism between the jasmonate
      (JA) and salicylate (SA) defence pathways. Pseudomonas syringae pv. tomato (Pto)
      DC3000, the causal agent of tomato bacterial speck disease, produces coronatine
      (COR) that stimulates stomata opening and facilitates bacterial leaf
      colonization. In Arabidopsis, stomata response to COR requires the COR co
      receptor AtJAZ2, and dominant AtJAZ2Deltajas repressors resistant to proteasomal
      degradation prevent stomatal opening by COR. Here, we report the generation of a
      tomato variety resistant to the bacterial speck disease caused by PtoDC3000
      without compromising resistance to necrotrophs. We identified the functional
      ortholog of AtJAZ2 in tomato, found that preferentially accumulates in stomata
      and proved that SlJAZ2 is a major co-receptor of COR in stomatal guard cells.
      SlJAZ2 was edited using CRISPR/Cas9 to generate dominant JAZ2 repressors lacking
      the C-terminal Jas domain (SlJAZ2Deltajas). SlJAZ2Deltajas prevented stomatal
      reopening by COR and provided resistance to PtoDC3000. Water transpiration rate
      and resistance to the necrotrophic fungal pathogen Botrytis cinerea, causal agent
      of the tomato gray mold, remained unaltered in Sljaz2Deltajas plants. Our results
      solve the defence trade-off in a crop, by spatially uncoupling the SA-JA hormonal
      antagonism at the stomata, entry gates of specific microbes such as PtoDC3000.
      Moreover, our results also constitute a novel CRISPR/Cas-based strategy for crop
      protection that could be readily implemented in the field.

PMID- 30183126
TI  - A pilot study of immunotherapy in dogs with atopic dermatitis using a mannan
      Dermatophagoides farinae allergoid targeting dendritic cells.
AB  - BACKGROUND: Polymerized allergoids coupled to nonoxidized mannan (PM-allergoids)
      are novel allergen preparations used for immunotherapy. OBJECTIVE: To evaluate PM
      allergoids as an alternative immunotherapy for dogs with canine atopic dermatitis
      (cAD) associated with serological responses to Dermatophagoides farinae
      allergens. ANIMALS: Sixteen dogs with history and clinical signs of cAD; positive
      on serum allergen specific IgE testing to D. farinae. Twelve dogs were, in
      addition, positive to Acarus siro and/or Lepidoglyphus destructor. METHODS AND
      MATERIALS: A prospective pilot study with no control group. PM-allergoids were
      administered by subcutaneous injection over a 10 month period. A pruritus Visual
      Analog Scale (pVAS) and medication scores were evaluated. Adverse reactions were
      recorded. RESULTS: The median value of the pVAS of the dogs decreased from 0.6 to
      0.2 with a median of 67% improvement over the first three months (P < 0.0001).
      The individual improvement for each dog was greater than 60%. No major adverse
      effects were observed. CONCLUSIONS AND CLINICAL IMPORTANCE: Allergen-specific
      immunotherapy using an allergoid coupled to nonoxidized mannan may be an
      effective alternative for the management of cAD.

PMID- 30183128
TI  - miR1432-OsACOT (Acyl-CoA thioesterase) module determines grain yield via
      enhancing grain filling rate in rice.
AB  - Rice grain filling rate contributes largely to grain productivity and
      accumulation of nutrients. MicroRNAs (miRNAs) are key regulators of development
      and physiology in plants and become a novel key target for engineering grain size
      and crop yield. However, there is little studies, so far, showing the miRNA
      regulation of grain filling and rice yield, in consequence. Here, we show that
      suppressed expression of rice miR1432 (STTM1432) significantly improves grain
      weight by enhancing grain filling rate and leads to an increase in overall grain
      yield up to 17.14% in a field trial. Molecular analysis identified rice Acyl-CoA
      thioesterase (OsACOT), which is conserved with ACOT13 in other species, as a
      major target of miR1432 by cleavage. Moreover, overexpression of miR1432
      resistant form of OsACOT (OXmACOT) resembled the STTM1432 plants, that is, a
      large margin of an increase in grain weight up to 46.69% through improving the
      grain filling rate. Further study indicated that OsACOT was involved in
      biosynthesis of medium-chain fatty acids. In addition, RNA-seq based
      transcriptomic analyses of transgenic plants with altered expression of miR1432
      demonstrated that downstream genes of miR1432-regulated network are involved in
      fatty acid metabolism and phytohormones biosynthesis and also overlap with the
      enrichment analysis of co-expressed genes of OsACOT, which is consistent with the
      increased levels of auxin and abscisic acid in STTM1432 and OXmACOT plants.
      Overall, miR1432-OsACOT module plays an important role in grain filling in rice,
      illustrating its capacity for engineering yield improvement in crops.

PMID- 30183129
TI  - Rhizosheath formation and involvement in foxtail millet (Setaria italica) root
      growth under drought stress.
AB  - The rhizosheath, a layer of soil particles that adheres firmly to the root
      surface by a combination of root hairs and mucilage, may improve tolerance to
      drought stress. Setaria italica (L.) P. Beauv. (foxtail millet), a member of the
      Poaceae family, is an important food and fodder crop in arid regions and forms a
      larger rhizosheath under drought conditions. Rhizosheath formation under drought
      conditions has been studied, but the regulation of root hair growth and
      rhizosheath size in response to soil moisture remains unclear. To address this
      question, in this study we monitored root hair growth and rhizosheath development
      in response to a gradual decline in soil moisture. Here, we determined that a
      soil moisture level of 10%-14% (w/w) stimulated greater rhizosheath production
      compared to other soil moisture levels. Root hair density and length also
      increased at this soil moisture level, which was validated by measurement of the
      expression of root hair-related genes. These findings contribute to our
      understanding of rhizosheath formation in response to soil water stress.

PMID- 30183130
TI  - Genome-wide identification of loci affecting seed glucosinolate contents in
      Brassica napus L.
AB  - Glucosinolates are amino acid-derived secondary metabolites that act as chemical
      defense agents against pests. However, the presence of high levels of
      glucosinolates severely diminishes the nutritional value of seed meals made from
      rapeseed (Brassica napus L.). To identify the loci affecting seed glucosinolate
      content (SGC), we conducted genome-wide resequencing in a population of 307
      diverse B. napus accessions from the three B. napus ecotype groups, namely,
      spring, winter, and semi-winter. These resequencing data were used for a genome
      wide association study (GWAS) to identify the loci affecting SGC. In the three
      ecotype groups, four common and four ecotype-specific haplotype blocks (HBs) were
      significantly associated with SGC. To identify candidate genes controlling SGC,
      transcriptome analysis was carried out in 36 accessions showing extreme SGC
      values. Analyses of haplotypes, genomic variation, and candidate gene expression
      pointed to five and three candidate genes in the common and spring group-specific
      HBs, respectively. Our expression analyses demonstrated that additive effects of
      the three candidate genes in the spring group-specific HB play important roles in
      the SGC of B. napus.

PMID- 30183131
TI  - 1 H-NMR metabolomics for evaluating the protective effect of Clinacanthus nutans
      (Burm. f) Lindau water extract against nitric oxide production in LPS-IFN-gamma
      activated RAW 264.7 macrophages.
AB  - INTRODUCTION: Clinacanthus nutans, a small shrub that is native to Southeast
      Asia, is commonly used in traditional herbal medicine and as a food source. Its
      anti-inflammation properties is influenced by the metabolites composition, which
      can be determined by different binary extraction solvent ratio and extraction
      methods used during plant post-harvesting stage. OBJECTIVE: Evaluate the
      relationship between the chemical composition of C. nutans and its anti
      inflammatory properties using nuclear magnetic resonance (NMR) metabolomics
      approach. METHODOLOGY: The anti-inflammatory effect of C. nutans air-dried leaves
      extracted using five different binary extraction solvent ratio and two extraction
      methods was determined based on their nitric oxide (NO) inhibition effect in
      lipopolysaccharide-interferon-gamma (LPS-IFN-gamma) activated RAW 264.7
      macrophages. The relationship between extract bioactivity and metabolite profiles
      and quantifications were established using 1 H-NMR metabolomics and liquid
      chromatography-tandem mass spectrometry (LC-MS/MS). The possible metabolite
      biosynthesis pathway was constructed to further strengthen the findings. RESULTS:
      Water and sonication prepared air-dried leaves possessed the highest NO
      inhibition activity (IC50  = 190.43 +/- 12.26 MUg/mL, P < 0.05). A total of 56
      metabolites were tentatively identified using 1 H-NMR metabolomics. A partial
      least square (PLS) biplot suggested that sulphur containing glucoside, sulphur
      containing compounds, phytosterols, triterpenoids, flavones and some organic and
      amino acids were among the potential NO inhibitors. LC-MS/MS targeted
      quantification further supported sonicated water extract was among the extract
      that possessed the most abundant C-glycosyl flavones. CONCLUSION: The present
      study may serve as a preliminary reference for the selection of optimum extract
      in further C. nutans in vivo anti-inflammatory study.

PMID- 30183132
TI  - Can radiation oncologists learn to be better leaders? Outcomes of a pilot
      Foundations of Leadership in Radiation Oncology program for trainees delivered
      via personal electronic devices.
AB  - INTRODUCTION: There has been no systematic attempt to enhance leadership capacity
      within radiation oncology as an integrated component of training. This pilot
      study examines an intervention to introduce basics of leadership learning to
      radiation oncology trainees. METHODS: A case-based learning tool was designed for
      delivery via trainees' personal electronic devices. Eight typical workplace case
      scenarios representing leadership challenges were followed by multiple choice
      questions, key learning points and hyperlinks to relevant resources. Cases were
      automatically sent every few days over 4 weeks and participants' responses
      anonymously collated by the delivery platform (QStream). In addition, an online
      survey was sent at completion of the program to capture trainees' perspectives on
      the utility of this tool. RESULTS: Thirty-seven of 45 (82%) trainees
      participated: 21 females and 16 males. Twenty-six of 37 (70%) starting the
      program completed it. Sixteen (62% of 'completers') responded to the post-program
      survey. Fourteen of 16 (87.5%) agreed to the program and helped them identify
      ways they were already exhibiting leadership. Eleven of 16 (68.8%) agreed they
      had acquired knowledge that could assist them in being better leaders. Fifteen of
      16 said the program made them consider future leadership possibilities in
      radiation oncology. Fourteen of 15 enjoyed the digital format. Most suggestions
      for improvement linked to a desire for more interactivity in learning these
      skills. CONCLUSION: Piloting an online tool designed to introduce foundation
      leadership concepts to radiation oncology trainees has provided useful feedback
      to guide further development in this area. Although this method had high
      feasibility, it revealed the need for additional interactive methods for
      leadership learning.

PMID- 30183133
TI  - Dual-energy contrast-enhanced CT to evaluate scaphoid osteonecrosis with surgical
      correlation.
AB  - To evaluate the validity of contrast enhanced dual energy CT using a lung
      perfusion algorithm in assessing for post-traumatic scaphoid proximal pole
      avascular necrosis. From Aug 2013 to Aug 2016, 18 patients (19 wrists, 16 males,
      2 females, mean age 28 years) were assessed as high-risk for proximal pole
      scaphoid avascular necrosis by a single surgeon following a scaphoid fracture and
      were referred for contrast-enhanced dual energy CT. 8 wrists had specimens sent
      for correlative histological analysis and 11 were correlated with operative
      notes. Eight surgical specimens were sent to histology and showed a 100%
      correlation (8/8) with the DECT findings. The remaining 11 wrists that did not
      have a specimen sent had in-surgery findings that also correlated with DECT. A
      single case was discrepant (1/11) due to presence of an intra-osseous ganglion,
      which was reported as osteonecrosis on CT, but considered viable at surgery. No
      case was called viable on CT that proved to be necrotic at either surgery or
      histologically. Contrast-enhanced dual energy CT using a perfusion algorithm is
      an innovative and promising method in evaluating viability of the post-trauma
      proximal pole of scaphoid.

PMID- 30183134
TI  - Photodynamic Therapy Based on Nanoscale Metal-Organic Frameworks: From Material
      Design to Cancer Nanotherapeutics.
AB  - Photodynamic therapy (PDT) is a highly effective, noninvasive, highly selective
      method for cancer treatment. Nanoscale metal-organic frameworks (NMOFs) are a
      type of crystalline hybrid material composed of metal centers and organic
      linkers. Owing to their adjustable structure, easy modification, permanent pores,
      and good biocompatibility, NMOFs, as either nanophotosensitizers or
      photosensitizer nanocarriers, have been used in PDT. In this article, we
      summarize the recent progress in MOF-based nanomaterials for tumor PDT. The MOF
      based nanomaterials might open up new avenues for the fabrication of new types of
      photosensitizers for PDT.

PMID- 30183135
TI  - Osteonecrosis in children with acute lymphoblastic leukemia: A report from
      Children's Cancer Hospital Egypt (CCHE).
AB  - BACKGROUND: As survival rates for children with acute lymphoblastic leukemia
      (ALL) improve, awareness of treatment complications becomes important.
      Osteonecrosis (ON) is a serious disabling complication in treated ALL patients.
      The aim of the study was to define the frequency of ON identified by magnetic
      resonance imaging (MRI) and to study the risk factors for ON. PATIENTS AND
      METHODS: The frequency of ON was evaluated retrospectively in 858 patients with
      ALL who were diagnosed at Children's Cancer Hospital of Egypt from January 2009
      to December 2012. Patients were treated with St Jude Total Therapy Study XV.
      RESULTS: Of 858 patients evaluated, 665 were eligible for the study and 65 (9.7%)
      developed ON. The cumulative 5-year incidence of ON was 11.96% (SE, 0.131%). Of
      154 patients aged 10 years and older, 40 (26%) developed ON. The mean age of
      patients with ON was 10.7 years. The prognostic factors with a significant
      relationship with ON were age 10 years and older (P = 0.0001) and intermediate
      /high-risk group (P = 0.0001). However, gender did not have a significant
      relationship. At the onset of ON, the mean cumulative dexamethasone dose was 796
      mg/m2 , and the mean total corticosteroid dose, calculated as prednisolone
      equivalence, was 6,431 mg/m2 . Out of 43 patients who developed ON while on
      corticosteroid therapy, 36 (84%) required dexamethasone dose modification and/or
      discontinuation. CONCLUSION: The frequency of ON among the studied patients was
      9.7%. Risk factors with a significant association with ON were older age and more
      intensive corticosteroid therapy.

PMID- 30183136
TI  - Therapy-related acute myeloid leukemia following treatment for cancer in
      childhood: A population-based registry study.
AB  - BACKGROUND: Therapy-related acute myeloid leukemia (t-AML) is defined as AML that
      develops after exposure to cytotoxic chemotherapy and/or radiation therapy. There
      is a paucity of available literature, particularly in regard to t-AML following
      childhood cancer. Our aim was to describe the risk of t-AML among children
      treated for other cancers and their subsequent survival. PROCEDURE: We utilized
      data from the population-based Australian Childhood Cancer Registry to examine
      all childhood patients (<15 years at diagnosis) treated with chemotherapy and/or
      radiotherapy for cancers other than AML who received a subsequent diagnosis of
      AML between 1983 and 2014. Standardized incidence ratios (SIRs) were calculated
      to approximate the relative risk of being diagnosed with AML compared to the
      general population. Estimates of 5-year observed survival were obtained using the
      Kaplan-Meier method, with differences determined by the log-rank test. RESULTS:
      Fifty-eight of 11,753 patients in the study cohort (0.5%) were diagnosed with t
      AML, an almost 50-fold higher risk than expected (SIR = 45.6, 95% confidence
      interval [CI] = 35.3-59.0). Five-year observed survival from the date of t-AML
      diagnosis was 31.2% (95% CI = 19.6-43.5%). A significant survival advantage was
      found for patients who underwent hematopoietic stem cell transplantation (HSCT)
      following diagnosis of t-AML, with a 5-year survival of 52.4% (29.7-70.9%)
      compared to 5.7% (0.4-22.6%) for those who did not have HSCT (P < 0.001).
      CONCLUSIONS: Although rare, t-AML is an important potential late effect of
      childhood cancer therapy. Prognosis is generally poor, with HSCT offering some
      survival benefit.

PMID- 30183137
TI  - DNA recognition by Arabidopsis transcription factors ABI3 and NGA1.
AB  - B3 transcription factors constitute a large plant-specific protein superfamily,
      which plays a central role in plant life. Family members are characterized by the
      presence of B3 DNA-binding domains (DBDs). To date, only a few B3 DBDs were
      structurally characterized; therefore, the DNA recognition mechanism of other
      family members remains to be elucidated. Here, we analyze DNA recognition
      mechanism of two structurally uncharacterized B3 transcription factors, ABI3 and
      NGA1. Guided by the structure of the DNA-bound B3 domain of Arabidopsis
      transcriptional repressor VAL1, we have performed mutational analysis of the ABI3
      B3 domain. We demonstrate that both VAL1-B3 and ABI3-B3 recognize the Sph/RY DNA
      sequence 5'-TGCATG-3' via a conserved set of base-specific contacts. We have also
      solved a 1.8 A apo-structure of NGA1-B3, DBD of Arabidopsis transcription factor
      NGA1. We show that NGA1-B3, like the structurally related RAV1-B3 domain, is
      specific for the 5'-CACCTG-3' DNA sequence, albeit tolerates single base pair
      substitutions at the 5'-terminal half of the recognition site. Employing distance
      dependent fluorophore quenching, we show that NGA1-B3 binds the asymmetric
      recognition site in a defined orientation, with the 'N-arm' and 'C-arm'
      structural elements interacting with the 5'- and 3'-terminal nucleotides of the
      5'-CACCTG-3' sequence, respectively. Mutational analysis guided by the model of
      DNA-bound NGA1-B3 helped us identify NGA1-B3 residues involved in base-specific
      and DNA backbone contacts, providing new insights into the mechanism of DNA
      recognition by plant B3 domains of RAV and REM families. DATABASES: RCSB Protein
      Data Bank, accession number 5OS9.

PMID- 30183138
TI  - Intramolecular Proton and Charge Transfer of Pyrene-based trans-Stilbene
      Salicylic Acids Applied to Detection of Aggregated Proteins.
AB  - Two analogues to the fluorescent amyloid probe 2,5-bis(4'-hydroxy-3'-carboxy
      styryl)benzene (X-34) were synthesized based on the trans-stilbene pyrene
      scaffold (Py1SA and Py2SA). The compounds show strikingly different emission
      spectra when bound to preformed Abeta1-42 fibrils. This remarkable emission
      difference is retained when bound to amyloid fibrils of four distinct proteins,
      suggesting a common binding configuration for each molecule. Density functional
      theory calculations show that Py1SA is twisted, while Py2SA is more planar.
      Still, an analysis of the highest occupied molecular orbitals (HOMOs) and lowest
      unoccupied molecular orbitals (LUMOs) of the two compounds indicates that the
      degree of electronic coupling between the pyrene and salicylic acid (SA) moieties
      is larger in Py1SA than in Py2SA. Excited state intramolecular proton transfer
      (ESIPT) coupled-charge transfer (ICT) was observed for the anionic form in polar
      solvents. We conclude that ICT properties of trans-stilbene derivatives can be
      utilized for amyloid probe design with large changes in emission spectra and
      decay times from analogous chemical structures depending on the detailed physical
      nature of the binding site.

PMID- 30183139
TI  - Gamma-Tocotrienol Attenuates the Hepatic Inflammation and Fibrosis by Suppressing
      Endoplasmic Reticulum Stress in Mice.
AB  - SCOPE: Gamma-tocotrienol (gammaT3), an unsaturated isoform of vitamin E, is
      implicated in the hepatoprotective effects. The aim is to determine the
      effectiveness of gammaT3 on nonalcoholic fatty liver disease (NAFLD). METHODS AND
      RESULTS: C57BL/6 male mice are fed a diet containing high fat (45%) and
      cholesterol (0.2%) along with sucrose drink (HFCS) or HFCS diet supplemented with
      0.1% gammaT3 (HFCS + gammaT3). The inclusion of gammaT3 robustly decreases the
      HFCS diet-induced de novo lipogenesis (DNL), ER stress, and inflammation leading
      to reduced hepatic steatosis and fibrosis. Next, mice are fed a methionine- and
      choline-deficient (MCD) diet or MCD diet with gammaT3 (MCD + gammaT3). The
      gammaT3 supplementation significantly reduces the MCD diet-induced hepatic ER
      stress and fibrosis despite the minimal impact on steatosis. To further
      investigate the role of ER stress, the mice with genetic ablation of CHOP are fed
      an MCD or MCD + gammaT3 diet. CHOP deletion abolishes the gammaT3-mediated
      suppression of hepatic fibrosis, suggesting that modulation of ER stress is a
      prerequisite to inhibit hepatic inflammation and fibrosis. CONCLUSION: gammaT3
      supplementation is effective in attenuating NAFLD and fibrosis through a
      synergistic mechanism of decreased DNL and hepatic ER stress. This work strongly
      supports the translational potential of gammaT3 supplementation against NAFLD.

PMID- 30183140
TI  - Association between insomnia and personality traits among Japanese patients with
      type 2 diabetes mellitus.
AB  - AIMS/INTRODUCTION: Insomnia is associated with type 2 diabetes mellitus, and
      results in a low quality of life. There are several known relationships between
      insomnia and personality. Thus, we clarified the association between some
      personality traits and insomnia among Japanese type 2 diabetes mellitus patients.
      MATERIALS AND METHODS: The participants were 504 type 2 diabetes mellitus
      patients (mean age 63.9 +/- 12.5 years). Sleep disturbance and personality traits
      were evaluated using the Pittsburgh Sleep Quality Index-Japanese version and the
      Ten-Item Personality Inventory Japanese version, respectively. Lifestyle factors,
      glycated hemoglobin levels and depressive status of the patients were also
      included in the analyses. RESULTS: Among the 504 participants with type 2
      diabetes mellitus, 154 (30.6%) showed probable insomnia. After adjustment for
      confounders, being female, living alone, high body mass index and "high
      neuroticism" were found to be significantly correlated with current insomnia. No
      other relationships between insomnia and glycated hemoglobin or lifestyle
      factors, such as smoking, drinking alcohol or exercise frequency, were found.
      CONCLUSIONS: The prevalence of insomnia in individuals with type 2 diabetes
      mellitus was high, and the risk factors included some personality factors. Future
      prospective studies are required to confirm the therapeutic effects of behavioral
      interventions for insomnia in patients with type 2 diabetes mellitus.

PMID- 30183141
TI  - Comparison of the pharmacological activity of idarubicin and doxorubicin for
      retinoblastoma.

PMID- 30183143
TI  - Efficacy of levofloxacin against biofilms of Pseudomonas aeruginosa isolated from
      patients with respiratory tract infections in vitro.
AB  - Microbial biofilms are formed in a variety of clinical situations and increase
      antibiotic resistance of the pathogen by almost ~1,000 times. The effect of
      levofloxacin (OFLX) on the biofilms of Pseudomonas aeruginosa strain PAO1 and the
      clinical isolates was investigated by crystal violet staining and confocal laser
      scanning microscope. The transcriptional alteration in the PAO1 biofilms upon
      OFLX treatment was also analyzed by RNA sequencing (RNA-seq). We found that while
      OFLX significantly inhibited P. aeruginosa biofilm formation in a dose-dependent
      manner, it could not completely eradicate preformed biofilms even at higher
      concentrations. RNA-seq revealed that PAO1 genes related to metabolism, formation
      of secondary metabolites, and quorum sensing biosynthesis were differentially
      expressed in the biofilms treated with OFLX. Our data might be useful in
      determining the optimum OFLX concentration needed for P. aeruginosa biofilm
      inhibition and eradication in patients with respiratory tract infections.

PMID- 30183142
TI  - Functional near-infrared spectroscopy study of the neural correlates between
      auditory environments and intellectual work performance.
AB  - INTRODUCTION: Many people spend a considerable amount of time performing
      intellectual activities within auditory environments that affect work efficiency.
      To investigate auditory environments that improve working efficiency, we
      investigated the relationship between brain activity and performance of the
      number memory task in environments with and without white noise using functional
      near-infrared spectroscopy (fNIRS). METHODS: Twenty-nine healthy subjects (aged
      21.9 +/- 1.4 years) performed the number memory task in both the white noise and
      silent environments. Cerebral blood flow changes during the task were measured
      using an ETG-7100 fNIRS system (Hitachi, Ltd., Tokyo, Japan). The psychological
      states of the subjects were also estimated by subjective ratings of the
      pleasantness of the auditory environment. Then, they were divided into three
      groups based on their task scores. The differences in the cerebral blood flow
      (CBF) changes, functional connection strength, and the subjects' feelings of
      pleasantness to the noise between the subject groups were analyzed and discussed.
      RESULTS: The first group felt that the white noise was pleasant, which
      strengthened the bilateral functional connections between the brain regions
      related to the memory task. Therefore, the subjects' task performance improved in
      the white noise environment. Although the second group felt that the white noise
      was uncomfortable, the frontal regions related to attention control were more
      activated in the white noise environment to sustain the task performance in the
      noisy environment. The third group felt that the white noise was unpleasant, and
      their CBF decreased in that environment, which was associated with deteriorated
      task performance. CONCLUSIONS: Task performance was closely related to the
      subjects' feelings of pleasantness to the noise. The results of the analysis of
      the CBF changes and functional connectivity suggested that the effects of the
      white noise on brain activity differed among the three groups.

PMID- 30183144
TI  - Historical and Hygienic Aspects on Roles of Quality Requirements for Antibiotic
      Products in Japan : Part 3-Introduction of Technologyand Knowledge in the
      Production Process and Quality Control of Penicillin from the United States of
      America.
AB  - In order to investigate the roles of quality requirements for antibiotic products
      in Japan, from historical and hygienic aspects, we examined and analyzed how
      technology and knowledge in the production and quality control of penicillin were
      introduced from the United States of America, applied, and further
      developed.Owing to the strong support of Colonel Crawford Sams, the chief of the
      Public Health and Welfare Section of the Supreme Commander for Allied
      Power/General Headquarters, via the Ministry of Welfare in Japan, the technology
      and knowledge were acquired from an experienced leader, Dr. Jackson W. Foster,
      and as a result, domestic production of penicillin was successfully achieved in
      amounts required to meet national demands sufficiently within three years in a
      devastated post-war-torn Japan.Based on the consensus that penicillin should be
      dealt with as "biological products" similar to vaccines and antisera, the quality
      standards for penicillin were enacted as the "Minimum Requirements for Penicillin
      (MRP)" on the 1st of May 1947. Due to the development of penicillin production
      technology, the quality standards of penicillin provided by the MRP were revised
      often to higher levels ; content of the active element from no less than 60
      units/mg (purity 3.8%) to no less than 1,430 units/mg (purity 89.7%). Regarding
      the penicillin preparations, the content of the active ingredient per vial was
      changed from 30,000 units at the beginning, to 100,000 units in January 1948, to
      3,000,000 units in December 1950, and two preparations containing 200,000 units
      and 1,000,000 units per vial are currently available, according to clinical
      convenience.

PMID- 30183145
TI  - The Change of Reference to Post-Marketing Surveillance Based on the Sequence of
      Revising the Pharmaceutical Affairs Law.
AB  - The present Pharmaceutical Affairs Law (PAL) was promulgated in October 1960 and
      enforced in February 1961.Thereafter, PAL has been frequently revised, was
      renamed the Pharmaceuticals and Medical Devices Act (PMD Act) in November 2013,
      and the PMD Act was enforced in November 2014. It describes the change of
      reference to Post-Marketing Surveillance (PMS) based on the sequence of revisions
      of PAL for approximately 50 years. Although the purpose of PAL in 1960 was "to
      control and regulate drugs, quasi-drugs, cosmetics and medical devices (drugs,
      etc.), and to contrive proper use," it did not include rules regarding PMS.
      Thereafter, "to assure the quality, efficacy and safety of drugs, etc.," "to
      promote research and development of orphan drugs, etc." and "to regulate
      designated substances" were added to the purpose of PAL over a period of time. At
      the time of establishing the PMD Act, "to assure the quality, efficacy and safety
      of regenerative products, to promote their research and development, and to
      prevent the onset and spread of hazards to public health and hygiene through the
      use of drugs, etc. "was added to the purpose. Simultaneously, the matters of
      control and regulation using PAL were increased whenever PAL was
      revised.Additionally, the PMS systems, such as adverse drug reactions reporting,
      drug reevaluation and drug reexamination, and the Good Post-Marketing
      Surveillance Practice (GPMSP) regarding the enforcement standards of PMS, etc.
      were initiated by regulatory directions and legislated after their establishment.
      Moreover, an infection reporting system and early-phase pharmcovigilance, etc.
      were added to the PMS systems. Furthermore, GPMSP was divided into the Good
      Vigilance Practice (GVP) for marketing license conditions and the Good Post
      Marketing Study Practice (GPSP) for enforcement standards regarding post
      marketing investigations and clinical trials, and both are regulated.

PMID- 30183146
TI  - Transition of Psychotropic Drugs in Japanese Pharmacopoeia (JP) (Part 17)
      Transitions in the Standards and Test Methods of Valproic Acid and Sodium
      Valproate in Japanese Pharmacopoeia (JP), Pharmacopoeia of the USA (USP), British
      Pharmacopoeia (BP), and the Knowledge and Judgment aboutJapanese Valeriana, and
      Valproic Acid from Valeric Acid
AB  - Valproic acid (VPA) and sodium valproate (VPA-Na) are used for the treatment of
      various things today, such as epilepsy and manic-depressive states. Moreover, use
      has expanded to a variety of applications, such as the prevention of migraine
      headaches. As a result, a high demand has been maintained. The chemical structure
      is a branching low-grade saturated fatty acid, which is simpler than other
      psychotropic drugs. VPA is called 2-propyl-pentanoic acid and 2-propyl-valeric
      acid under the IUPAC system, and is derived from Valeric acid. This time, the
      author researched transitions in the standards and testing methods for VPA and
      VPA-Na in JP, USP and BP. It was found that each country's pharmacopoeia
      described a detection test for substances related to VPA. It can be explained
      that VPA is derived from Valeric acid based on the test contents. Valeric acid is
      a component of Japanese Valeriana and Valerian root. It is believed that there is
      a sense of value as the origin of VPA is Japanese Valeriana and Valeriana root.

PMID- 30183147
TI  - History of French Pharmaceutical Education from 16th Century up to the
      Present??Study on Japanese Pharmaceutical Education : Comparison between Japan
      and France - Pharmaceutical Education System.
AB  - After the long isolation in the Edo era, the new Meiji government tried to import
      science and culture from western countries. In the field of medical science,
      Kanpo, Chinese medicine, was abolished and western medicine was introduced in
      Japan. A medical system was established in 1874, but the division of prescribing
      medicines and dispensing them had not been introduced yet, and this situation
      prevented the increase in newborn pharmacists and solid pharmaceutical education
      for a long time. However, when the division of prescribing and dispensing
      medicines started in the late 1980s, the demand for pharmacists increased and a
      six-year pharmaceutical education system was introduced in 2006. The core
      curriculum that was established about 10 years ago had many problems, but the
      system was revised in 2013. The goal of the efforts is to improve the situation
      regarding the quality, quantity and contents of clinical pharmaceutical education
      for the new generation of pharmacists to come over the next 10 years. It is
      important to look at the pharmaceutical education of Japan in light of that of
      France, where the division of prescribing and dispensing medicine, and the
      pharmacy itself had been established in medieval times, focusing on the history
      of the educational system and requirements for pharmacists.

PMID- 30183148
TI  - Transition of Psychotropic Drugs in Japanese Pharmacopoeia (JP) (Part 18) The
      Study for New Knowledge and Decisions regarding Cultivation Method for Japanese
      Valerian (Kisso).
AB  - In Japanese Pharmacopoeia (JPXVII 2016), there is a description about Kanokoso,
      "This item is the root and rootstock of Kanokoso Valeriana fauriei Briquet
      (Valerianaceae). Kanokoso Valeriana fauriei Briquet is referring to Ezokanokoso
      Valeriana fauriei forma yezoensis Hara, which is the same variety. The Hokkai
      kisso currently cultivated in Japan is the Ezokanokoso variety. The author
      analyzed the history of the variety of Japanese Valerian previously cultivated,
      but it's incomplete. To maintain the quality and efficacy of a medicine, it is
      important to disseminate information regarding the origin of the crude drug. To
      ensure the quality of Kanokoso and stable efficacy of the medicine, it's
      indispensable to maintain the original plant variety when cultivated.The author
      obtained the following knowledge during research. The variety cultivated in
      Kanagawa early in the Showa era was Japanese Valerian, sometimes being two kinds,
      lobule and round leaf. It is presumed that the original variety cultivated in
      Kanagawa early in the Showa era was Hokkai-kisso.The ingredients of the variety
      of Japanese Valerian cultivated and that which grows wild vary. The basis of the
      chemical structure of sesqui terpene kinds of alpha-Kessyl alcohol (KA) and
      Kessyl glycol diacetate (KGD), etc. has Kessane skeleton. It's this consistency
      and is gathered using the same type of system. The consistency is interesting.
      Pursuing the relation between the consistency and type of system is regarded as a
      problem. To obtain the same kind of ingredient and form from Hokkai-kisso in the
      current state seems difficult. To maintain today's quality of Hokkai-kisso and
      medicinal efficacy, it's important for continue to cultivating the plant by
      dividing the roots for replanting.

PMID- 30183149
TI  - "Terumeru," A Patent Medicine of the Late Edo Era-The Packaging, Efficacy
      Statement, and Dosage Form.
AB  - "Terumeru" was a patent medicine that an apothecary in Osaka sold as an
      expectorant and medicine for internal diseases towards the end of the Edo era.
      Due to its manufacturer, Gengendo, closing its expectorant business in the early
      Meiji era, further details are unknown. The author investigated Terumeru products
      dating back approximately 200 years. The objective of this study is to clarify
      what kind of patent medicine Terumeru was, and furthermore, compare it to other
      medicines with names spelled using katakana that were distributed around the same
      time as a topic of discussion.The characteristics of Terumeru were as follows :
      the dosage form was three times as much as that prescribed for similar drugs ;
      and although it was said to be of Dutch origin, the name of a Chinese clinician,
      Zhu Zhenheng, was cited on its efficacy statement and advertising. These findings
      revealed that there were problems with its formulation and inconsistency in its
      brand image. These reasons led to the conclusion that Terumeru was considered a
      katakana-named patent medicine during the pioneering days of pharmacology Japan.

PMID- 30183150
TI  - TECHNIQUES REQUIRED FOR GENERAL THORACIC SURGEON].

PMID- 30183151
TI  - [BRONCHOPLASTY].

PMID- 30183152
TI  - [THORACOSCOPIC MANAGEMENT OF PULMONARY ARTERY BLEEDING].

PMID- 30183153
TI  - PHENOMENON OF ATYPICAL DNA COMETS.
AB  - The phenomenon of atypical DNA comets in experiments using DNA comet assay is
      described and illustrated.The current hypotheses explaining the nature of
      atypical DNA comets and own vision of the issue areconsidered. The practical
      importance of the registration of atypical DNA comets in assessing the
      genotoxicity isdiscussed.

PMID- 30183154
TI  - Echocardiographic evaluation of diastolic dysfunction in young and healthy
      patients with psoriasis: A case-control study.
AB  - Psoriasis is a systemic inflammatory disease with a great prevalence in general
      population. The inappropriate activation of the cellular immune system has been
      hypothesized to be an independent cardiovascular risk factor, given the higher
      incidence of cardiovascular disorders in psoriatic patients. Echocardiographic
      abnormalities have been demonstrated too: the aim of our study was to evaluate
      the presence of preclinical cardiac dysfunction in a cohort of psoriatic patients
      without cardiovascular risk factors. We enrolled 52 patients with the diagnosis
      of chronic plaque psoriasis, compared with a control group not affected by any
      relevant systemic diseases and inflammatory disorders. In all patients and
      control group, echocardiographic conventional and tissue Doppler (TDI) studies
      were conducted. The analysis of echocardiographic parameters revealed normal
      dimension, mass and systolic function of the left ventricle. Left ventricular
      diastolic dysfunction was found in 36.5% patients in the psoriasis group versus
      0% in control group, and significant reduction of the E/A ratio was found also
      for the right ventricle. A significant increase of mitral regurgitation has been
      found in psoriatic patients (p=0.005). The early recognition of cardiovascular
      pre-clinic disease in psoriatic patients may guide a strict follow up and an
      early treatment, potentially improving cardiovascular prognosis.

PMID- 30183155
TI  - On a defective Mitraclip(r) system: Considerations on the medical device
      regulation in Europe.
AB  - The use of medical devices is constantly growing and constitutes a valid aid to
      ailing people because of remarkable technological advances. The regulations on
      their circulation in Italy and Europe are inspired by the principle of free
      circulation: it is sufficient for a device to have the CE logo for it to be
      freely commercialized in all European countries. These regulations that favors
      commerce also expose the sick to the risk of harm from defective devices that
      have not been suitably checked prior to commercial release. This paper reports a
      case of a defective MitraClip(r) Delivery System, discusses other episodes of
      similar device malfunctioning, and analyzes the European legislation on medical
      devices. In the author's opinion, a careful "control" policy for devices, an
      adequate care in device manufacturing, an appropriate evaluation of pre- and post
      marketing and suitable measures for the patient's safety are needed.

PMID- 30183156
TI  - Non-specific interstitial pneumonia and features of connective tissue disease:
      What are the consequences of a different point of view?
AB  - Patients with Interstitial Lung Disease (ILD) without a definitive diagnosis of
      connective tissue diseases (CTD) were historically described as Undifferentiated
      Connective Tissue Disease (UCTD-ILD). Recently a new classification, Interstitial
      Pneumonia with Autoimmune Features (IPAF), has been proposed. Aim of this study
      was to describe the prevalence, clinical characteristics and prognostic factors
      of UCTD and IPAF subjects in a cohort of Non-Specific Interstitial Pneumonia
      (NSIP) patients. This retrospective, observational study enrolled 102 adult
      patients characterized by NSIP pattern on High Resolution Computed Tomography,
      without a specific diagnosis of CTD. Three groups were identified according to
      patients' characteristics: IPAF, UCTD or idiopathic NSIP (iNSIP). Forty percent,
      27% and 55% of patients showed diagnostic criteria for IPAF, UCTD and iNSIP,
      respectively. No significant differences in age, gender, smoking habit, pulmonary
      function tests and three-year survival rate were observed among study groups.
      IPAF patients with antisynthetase antibodies positivity, in comparison to IPAF
      without antisynthetase antibodies positivity, showed more frequently an acute
      onset (44% vs 9%, p<0.012). The presence of autoimmune features seems not to be
      associated with better outcomes in NSIP patients. IPAF criteria seem to be more
      representative than UCTD criteria in identifying patients with autoimmune
      features. Further studies are needed to verify if IPAF should include patients
      with positive antisynthetase serology.

PMID- 30183157
TI  - Testosterone treatment in chronic heart failure. Review of literature and future
      perspectives.
AB  - Mounting evidence suggests that hormonal deficiencies (HD) have an important role
      in chronic heart failure (CHF). In particular, androgen depletion is common in
      men with CHF and is associated with increased morbidity and mortality. This
      review summarizes the current understanding of the complex relationship between
      CHF and testosterone, focusing on evidence derived from clinical trials that have
      investigated the role of testosterone in the treatment of CHF. A greater
      comprehension of this area will allow researchers and clinicians to plan future
      studies that improve current strategies to reduce mortality in this high-risk
      population. Online databases PubMed (Medline), Web of Science, and Scopus were
      searched for manuscripts published prior to June 2018 using key words "heart
      failure" AND "testosterone" OR "anabolism" OR "hormone" OR "replacement
      treatment". Manuscripts were collated, studied and carried forward for discussion
      where appropriate. In summary, findings from the literature demonstrate that
      testosterone treatment in CHF is a promising topic that requires further
      investigation.

PMID- 30183158
TI  - The impairment of the Growth Hormone/Insulin-like growth factor 1 (IGF-1) axis in
      heart failure: A possible target for future therapy.
AB  - Hormonal abnormalities are quite common in chronic heart failure (CHF). The most
      studied hormonal axis in CHF is the impairment of Growth Hormone (GH)/Insulin
      Growth Factor-1(IGF-1), which in turn is defined either by a blunted response to
      GH stimulation test or low serum IGF-1 values.  Several independent groups
      reported that the presence of an abnormal GH/IGF-1 status in CHF is associated
      with a more severe disease, impaired functional capacity and reduced Survival
      rates. After the first encouraging results, double -blind controlled trials
      showed a neutral effect of the GH administration in patients. However, further
      studies reported positive results, when a GH-therapy is implemented only in those
      patients presenting a GH deficiency (replacement therapy).

PMID- 30183159
TI  - Growth hormone in heart failure revisited: An old story retold.
AB  - Heart failure (HF) is a disease characterized by increasing prevalence, huge
      direct and indirect costs, and an ominous prognosis, worse than many cancers. At
      the beginning of the 90s, growth hormone (GH) was proposed as potential
      adjunctive therapy in HF mostly due to its growth-promoting, vasodilating, and
      anti-apoptotic actions. However, although several uncontrolled clinical studies
      showed that GH therapy improved several cardiovascular parameters, two robust
      trials failed to confirm these findings. Dwelling upon potential explanations for
      such apparent discrepancy led to the hypothesis that HF patients exhibit an
      inhomogeneous basal activity of the GH/insulin-like growth factor 1 (IGF-1) axis,
      ranging from GH/IGF-1 deficiency to GH resistance. This complex phenomenon was
      then reconsidered in the context of the so-called multiple hormone deficiency
      syndrome (MHD), that is the recognition that HF is characterized not only by the
      hyperactivation of several signaling pathways including the adrenergic, the renin
      angiotensin-aldosterone and cytokine systems, but also by a reduced anabolic
      drive leading to a state of anabolic/catabolic imbalance. Mounting evidence
      support the concept that such imbalance is not a mere epiphenomen, since it
      exerts a significant impact on clinical performance and more importantly, on
      survival. Therefore, the paradigm shift to reconsider HF as MHD represented the
      underpinning to implement clinical trials focused on hormone replacement
      therapies in congestive heart failure (CHF). With regard to GH replacement
      therapy, one controlled single-blind study yielded promising results, and we are
      currently conducting a double-blind controlled trial, as well a large Registry
      study to evaluate the impact of MHD on HF progression.

PMID- 30183160
TI  - The role of 3D echocardiographic imaging in the differential diagnosis of an
      atypical left atrial myxoma.
AB  - We describe a case of a left atrial myxoma atypical for its anatomical features
      and site of attachment. Although an initial multimodality imaging was performed,
      the diagnosis of myxoma was possible only by three dimensional echocardiography
      (3DE) which was able to identify the pedicle and the attachment at the base of
      the interatrial septum, close to the origin of right inferior pulmonary vein. In
      fact the 3DE can electronically section the structures and obtain unique planes
      useful in visualizing correctly the anatomical features of the myxomas and as a
      result, it facilitates the surgical decision planning. Even the anatomical
      appearance was uncommon at surgery and the diagnosis could be confirmed only by
      pathology.  This case highlights the diagnostic ability of the 3DE in similar
      challenging scenarios.

PMID- 30183161
TI  - A "long-standing" malpositioned pacing lead. Long-term follow-up after
      extraction.
AB  - Transvenous pacemaker (PM) catheters can be unintentionally placed in the left
      ventricle (LV) during the implantation procedure. An 8-year-old girl was
      discovered with a malpositioned pm wire, seven years after the implant. Trans
      thoracic echocardiogram revealed the lead traversing the inter-atrial septum,
      crossing the mitral valve and embedded in the basal lateral wall of the LV. This
      is a report of a 14-year long follow-up after the surgical extraction of the
      malpositioned PM lead.

PMID- 30183162
TI  - Occurrence of thymic pathology in two families. Is familial screening justified?
AB  - The familial occurrence of thymic pathology, even though rare, is widely reported
      in the literature and mainly concerns cases of familial autoimmune myasthenia
      gravis. Other less frequent cases of familial occurrence of thymoma, thymic
      carcinoid and thymic hyperplasia have been described. It seems that the familial
      occurrence is poorly recorded and thus its prevalence is underestimated. We
      report two families whose members presented different forms of thymic pathology
      and discuss the necessity of screening programs in family members of patients
      presenting a thymic lesion.

PMID- 30183163
TI  - EXTRACELLULAR VESICLES FROM BLOOD PLASMA STUDIED BY LOWVOLTAGE SCANNING ELECTRON
      MICROSCOPY.
AB  - Extracellular vesicles are subspherical membranous structures secreted by cells
      and enriched with differenttypes of biological molecules. The number and the
      molecular content of these structures depend on pathologicalconditions and the
      physiological state of the organism. Extracellular vesicles play an important
      role in intercellularcommunication and represent potential disease biomarkers.
      However, mechanisms of formation, functionsand morphological characteristics of
      extracellular vesicles are still studied insufficiently. Low voltage
      scanningelectron microscopy is a promising method to investigate extracellular
      vesicles, since it does not require conductivecoating and therefore enables a
      high-resolution visualization of morphological details of nanosized objects.This
      paper presents the results of low voltage scanning electron microscopy study of
      morphology and sizeof objects from blood plasma fractions.

PMID- 30183164
TI  - [THE ROLE OF JAPANESE NURSE PRACTITIONER IN THE PERIOPERATIVE MEDICINE].

PMID- 30183165
TI  - APOPTOSIS AND AUTOPHAGY IN HEPATOCARCINOMA CELLS INDUCED BY DIFFERENT FORMS OF
      LITHIUM SALTS.
AB  - Hepatocellular carcinoma (HCC) is one of the aggressive and resistant to drug
      therapy cancer. It is believedthat the development of HCC is correlated with
      dysregulation of programmed cell death. So, the search foreffective inducers of
      HCC cell death is very important. The aim of the work was to identify structural
      changesleading to HCC cell death when exposed to nanoscale and original forms of
      lithium salts. Using light and electronmicroscopy and flow cytometry, structural
      features of autophagy and apoptosis in HCC cells after their incubationwith
      various forms of lithium salts has been revealed. It is shown that a more
      pronounced effect onHCC-29 cells have nanoscale forms of lithium carbonate and
      lithium citrate. At the same time, nanoscale lithiumcitrate mainly induced
      apoptosis, and nanosized form of lithium carbonate, along with apoptosis,
      inducedautophagic death of HCC-29cells.

PMID- 30183166
TI  - COMPARISON OF CELL CYCLE DURATION IN THE MONOLAYER CELL LINEOF HEPATOMA ZAJDELA
      AND ITS SUBLINES 3H AND 9C CULTIVATED IN VITRO.
AB  - We studied proliferative features of cells in monolayer line of rat hepatoma
      Zajdela (the original, parent line)and in the sublines 3H and 9C cloned from
      different types of the colonies of the parental line. These sublinesalso differed
      by cytomorphometric parameters, by the types of colonies formed at recloning of
      these cells invitro, and by tumorogenicity at transplantation to a rat. Using a
      time-lapse video of native living cells, we analyzedthe cell cycle duration (CCD)
      and its relationship to a cell shape. Direct measurement of the CCD (a timeperiod
      from mitosis to mitosis) was performed in individual cells of non-synchronized
      cultures. Average valueof CCD in the parent Zajdela line appeared to be 14.6 +/-
      0.2 hours, that was higher (at P < 0.05) than in 3H and9C sublines (13.9 +/- 0.2
      and 13.5 +/- 0.3 hours, respectively). The analysis of CCD distribution histogram
      showedthat all three lines contained a common population of cells with CCD close
      to 14 hours. Besides, the parent cellline had about 1/3 of cells with a higher
      CCD (16.7 +/- 0.2 hours) while the subline 9C had, on the contrary,1/3 of cells
      with a lower CCD (12.6 +/- 0.1 hours). In addition, the parameters of cell area,
      coefficient of cellspreading and coefficient of cell polarization showed the
      highest correlation to CCD in cells of subline 3H,which are primarily fibroblast
      shaped cells (P < 0.01) : the larger the cell area, the longer the CCD; the
      moreflattened or polarized the cell is, the shorter its CCD. In the parental cell
      line and the subline 9C, both consistingof preferably epithelium-shaped cells,
      the correlation between CCD and cell shape was less pronounced andshowed the
      opposite direction, that may be explained by a difference in the origin of the
      cell lines. When consideringthe differences of CCD in the pairs of daughter
      cells, we introduce the concept of "the coefficient ofsymmetry of a cell
      division". The lower its value, the greater the similarity of CCD in a pair of
      daughter cells.Possible connection of the cell parameters studied in vitro to the
      tumorigenicity of these cells is discussed.

PMID- 30183167
TI  - THE SHORTENED ISOFORM OF a-TUBULIN IS DETECTED IN COMPLEX WITH PROTEASOMES.
AB  - The proteasome is a multi-subunit protein complex that serves as a major pathway
      for intracellular proteindegradation playing important functions in various
      biological processes. By using MALDI-ICR-mass-spectrometryand Western-blot
      analysis, we have shown the presence of shortened isoform of a-tubulin in
      complexwith the affinity-purified proteasomes from stable cell lines K562 and
      HEK293.

PMID- 30183168
TI  - [NEXT STAGE OF NATIONAL CLINICAL DATABASE].

PMID- 30183169
TI  - [RELATIONSHIP BETWEEN SURGICAL PROCEDURES AND THEIR SURGEON'S FEE].

PMID- 30183170
TI  - [ARBITRARY THOUGHTS OF AN OLD SURGEON].

PMID- 30183171
TI  - [WHAT IS MENTAL PREPARATION OF LEADER TO ACHIEVE GENDER EQUALITY OF IDEAL]?

PMID- 30183172
TI  - [BASIC RESEARCH BY SURGEONS].

PMID- 30183173
TI  - [TEAM APPROACH FOR SURGICAL TREATMENT, PRESENT STATUS AND PERSPECTIVE].

PMID- 30183174
TI  - [SMOOTH OPERATION DURING SURGERY WITH TEAM HEALTHCARE].
AB  - The operating room is the ultimate place for team healthcare. Physicians and
      staff must be conscious of the value of communication among team members so that
      surgeons can perform the best surgery. Surgeons also must focus completely on
      their work in the operating room, which may involve diverse tasks and complicated
      procedures. It is important to develop a consciousness of medical professionalism
      and the need for quality improvement in nursing and medical staff. It is
      necessary to share information, especially among job categories during minimally
      invasive surgical procedures, which have increased in number in recent years.
      Surgeons should clearly state that sudden equipment failures as well as
      complications could possibly occur on the informed consent forms. Medical
      professionals must respond to change and behave as a model group, functioning
      with the highest ethics and morality to maintain public trust. The author
      believes that we must work to build the team medical healthcare appropriate to
      the times.

PMID- 30183175
TI  - [PERIOPERATIVE TEAM COOPERATION IN OKAYAMA UNIVERSITY HOSPITAL].
AB  - In the past, most duties in perioperative management were carried out directly by
      surgeons themselves. However, in that conventional approach, the experience and
      knowledge of the responsible surgeon made a difference to the postoperative
      course. As hospital stays have become shorter in recent years, the preoperative
      hospitalization period is now only one to two days. It has become more difficult
      to prepare patients sufficiently, both physically and mentally, so that they
      undergo surgery with peace of mind. To overcome this situation, the Perioperative
      Management Center (PERIO) was opened at Okayama University Hospital in 2008, and
      patients undergoing esophageal cancer surgery have been accepted since 2009. In
      PERIO, multidisciplinary medical staff share information on patients throughout
      the organization, and team medical intervention is performed from the
      preoperative outpatient period. The introduction of PERIO has resulted in earlier
      postoperative resumption of mobility and shorter postoperative stays.
      Furthermore, according to a patient survey, PERIO provides an environment that
      enables patients to face surgery calmly. As the next stage, intraoperative and
      postoperative interventions in PERIO should be enhanced for a safer perioperative
      environment and even greater peace of mind for patients.

PMID- 30183176
TI  - [PERIOPERATIVE ORAL MANAGEMENT FOR ESOPHAGEAL CANCER AND LUNG CANCER SURGERY].
AB  - The effectiveness of perioperative oral management in decreasing the risk of
      postoperative pneumonia has been reported recently. We introduced perioperative
      oral management for esophageal cancer and lung cancer patients in 2014 and report
      here its current status and effectiveness for those patients in our institute.
      Every 100 cases of esophageal cancer and lung cancer patients treated surgically
      were classified into two groups, i.e., with or without perioperative oral
      management, and postoperative complications were compared retrospectively. In the
      lung cancer group, oral management prevented postoperative pneumonia
      significantly and shortened the length of hospital stays after surgery in
      comparison with the group without oral management. In the esophageal cancer
      group, there was little occurrence of postoperative pneumonia in either group.
      Numerous esophageal cancer patients who received neoadjuvant chemotherapy
      developed oral mucositis and received oral care treatment before surgery. Such
      treatment for oral mucositis likely improved the oral environment and prevented
      postoperative pneumonia. Other patients have also been introduced to the
      importance of oral care before chemotherapy. Perioperative oral management can
      prevent postoperative pneumonia in esophageal cancer and lung cancer patients.

PMID- 30183177
TI  - A novel DNase like compound that inhibits virus propagation from Asian Green
      Mussel, Perna viridis (Linn.).
AB  - Viral diseases are not only responsible for health related issues but also exert
      pressure on the State economy. Tropical and subtropical countries have more
      prevalence of virus associated pathological conditions such as chickenpox,
      adenovirus related infections, dengue, chickengunya, infectious mononucleosis,
      etc. Treatment options with effective antiviral drugs are limited and are
      unfortunately not free from undesirable effects. The Asian Green Mussel, Perna
      viridis (Linn.) (Mytilidae) are not only important for their evolutionary
      significance, high caloric index, ecological role in the sequestration of
      environmental pollutants especially heavy metals, but also are potential source
      for extraction of therapeutic and bioactive compounds. On the other hand,
      generally in bivalves, virus mediated mortality is not uncommon. In this study,
      we made a maiden attempt of exploring DNAse like bioactivity for natural non
      protenacious compound(s) extracted from P. viridis. Crude Methanol Extract (CME)
      of soft tissue of P. viridis and subsequently its partially purified component
      (PPC) possess exceptional ability to degrade indiscriminately both low and high
      molecular weight DNAs. In vitro digestions for1, 2 and 3 h with CME and PPC were
      found to be comparable to commercial (Sigma-Aldrich) enzyme, DNase I. Bioactive
      assays conducted to evaluate antimicrobial property, have shown that CME and PPC
      exclusively inhibit viral propagation. Nonetheless, CME & PPC have no effect on
      the propagation of bacteria (0 mm ZOI). These results indicate the possibility of
      a source of potential antiviral drug against DNA Group I viruses. Although our
      study does not provide any data to correlate to any physiological functions of
      these substances but provides a clue towards an important role in the biology of
      mussels. Any conclusion at this stage is premature. However, taking into
      consideration the significantly high virus mediated mortality in bivalves and the
      antiviral bioactivity of these substances, it appears that mussels have evolved
      some mechanisms to counteract some viruses.

PMID- 30183178
TI  - Genotoxicity and oxidative stress as biomarkers in fresh water mussel,
      Lamellidens marginalis (Lam.) exposed to monocrotophos.
AB  - Monocrotophos (MCP) is an organophosphate pesticide widely used in India for
      controlling various pests. In this study, we evaluated the oxidative stress and
      genotoxic potential of MCP on the freshwater mussel Lamellidens marginalis
      (Lamarck) after 7 days exposure and repair of the damaged DNA after 4 days
      recovery. The bivalves were exposed to 5.25 mg/L of MCP for 7 days and then
      allowed to recover for 4 days in pesticide-free water. Increase in the levels of
      thiobarbituric acid reactive substances was recorded in the gill, muscle, foot
      and mantle tissues. Cellular antioxidant defences i.e. antioxidant enzyme
      activities like catalase, superoxide dismutase, glutathione reductase and
      glutathione-S-transferase were used as biomarkers of oxidative stress. Altered
      activities of antioxidant enzymes were observed after exposure. There was a
      significant recovery in the antioxidative enzymes in the tissues after the
      recovery period. To monitor genotoxicity of MCP, we used micronucleus and comet
      assay. Increase in Olive tail moment in the gill cells of exposed mussels as
      compared to that of control ones indicated significant DNA damage. Our findings
      suggest that the MCP-induced oxidative stress may be contributing partly to
      genotoxic damage of gill cells. Thus, these biomarkers are found to be useful in
      evaluating the toxicity of MCP in mussels.

PMID- 30183179
TI  - Ovarian follicle structure of Zebrafish (Danio rerio Hamilton) after poly(2-ethyl
      2-oxazoline) exposure.
AB  - Poly(2-oxazoline)s have been widely known for their biomedical applications. They
      mimic natural systems and are generally used as liposomes, drug and gene delivery
      modules and also as pseudopeptides. In this study, effects of different doses (10
      and 50 mg/L) of poly(2-ethyl-2-oxazoline) on ovarian follicle ultrastructure of
      zebrafish were investigated with light and electron microscopy. After five days
      of administation, ovary tissues were disected and routine histological processes
      were done. Severe structural deformation at zona radiata, follicular epithelium
      and outer granulosa cell structure were observed. Edema at follicular epithelium,
      zona radiata and vitelline envelope stuructures were detected. Dose dependent
      increase in the number of immature oocytes were seen. Briefly, it was
      demonstrated that poly(2-ethyl-2-oxazoline) exposure affected oogenesis and
      caused apoptosis in zebrafish.

PMID- 30183180
TI  - Comparative virulence of strains of entomopathogenic nematodes for management of
      eggplant Grey Weevil, Myllocerus subfasciatus Guerin (Coleoptera: Curculionidae).
AB  - The Grey Weevil, Myllocerus subfasciatus Guerin, is an important emerging pest of
      quarantine significance in Solanaceae crops including the eggplant, Solanum
      melongena. Entomopathogenic nematodes (EPNs) have been shown to be a potential
      source of safe and effective control of M. subfasciatus. In this study, we
      determined the virulence of seven strains of EPNs (Nematoda: Rhabditida) viz.
      Heterorhabditis bacteriophora NBAIIHb105, H. indica NBAIIHi101, H. indica
      NBAIIHiMah, Steinernema abbasi NBAIISa01, Steinernema abbasi NBAIISa04, S.
      carpocapsae NBAIISc04 and S. glaseri NBAIISg01, with different foraging
      behaviour, against larvae of eggplant grey weevil, M. subfasciatus (Coleoptera:
      Curculionidae), and their suitability in five representative soils from the
      eggplant grown areas under laboratory conditions. All seven nematode strains
      caused >80% mortality of M. subfasciatus larvae at 40 IJs/cm2. LC90 values ranged
      between 21.18 and 46.41 IJs/cm2 at 96 h post-application, which corresponded to
      field concentrations between 2.1-4.6*109 IJs/ha. H. indica NBAIIHi101, S. glaseri
      NBAIISg01, S. abbasi NBAIISa01 and S. carpocapsae NBAIISc04 recorded higher grub
      mortality, compared to H. indica NBAIIHiMah, H. bacteriophora NBAIIHb05 and S.
      abbasi NBAIISa04 indicating existence of inter- and intra-specific variation in
      virulence. Response Surface Modelling (RSM) optimized LC and LT values for
      maximised larval mortality. RSM predicted a concentration of 58.05-62.54 IJs/cm2
      of these EPN (corresponding to a field dose of 5.8-6.2*109 IJs/ha) required for
      effecting 97.10-99.67% grub mortality, at 90-97 h of exposure. EPN strains
      performed better in terms of larval mortality in loamy sand, alluvial, mountain
      soil, red laterite compared to black cotton soils. Efficacy of EPN was positively
      correlated with the content of sand, and negatively with the clay content. It is
      possibly the first report that established the potential of local strains of EPNs
      with different foraging ability and their dosages for suppression of subterranean
      root feeding larvae of M. subfasciatus in five broad soil types of eggplant grown
      areas. Validation of this baseline data in real-time eggplant crop situations may
      help in evolving EPN-based viable management schedules for M. subfasciatus.

PMID- 30183181
TI  - [INFECTION PREVENTION AND CONTROL BY AN INFECTION CONTROL TEAM].
AB  - A multifaceted approach with four parallel strategies including infection
      prevention, accurate, prompt diagnosis and treatment, prudent use of
      antimicrobials, and prevention of transmission is required to reduce
      antimicrobial resistance in hospitals. As the exclusive use of a specific
      antibiotic causes resistance of microorganisms to it, balanced use of different
      antimicrobials is mandatory to reduce the selection pressure. In Hyogo College of
      Medicine, an antimicrobial stewardship program led by physicians and pharmacists
      facilitates hospital-wide heterogeneous antibiotic usage and has been associated
      with significant reductions in the isolation of multiple drug-resistant (MDR)
      organisms. To prevent the transmission of MDR organisms, standard precautions and
      transmission-based precautions should be enforced by infection control nurses.
      The establishment of a surveillance system for MDR organisms by laboratory
      personnel is important for the immediate intervention by the infection control
      team. In an infectious outbreak by MDR organisms, a multidisciplinary approach is
      necessary, and outbreaks of carbapenem-resistant Enterobacteriaceae infections in
      our institution were controlled with the support of the facility administration
      division.

PMID- 30183182
TI  - Effect of salinity and use of stress indices of morphological and physiological
      traits at the seedling stage in rice.
AB  - Rice (Oryza sativa L.) is the most important cereal crop and a major staple food
      for majority of the human populations worldwide. Rice crop is sensitive to
      salinity. In spite of large number of studies on salinity tolerance of rice, our
      knowledge on the overall effect of salinity on rice seedling growth is limited.
      Improvement in salt tolerance of crop plants remains indescribable, largely due
      to the fact that salinity is a complex trait which affects almost every aspect of
      the physiology, biochemistry and genomics of plants. The present investigation
      was conducted to establish the relationship between various morphological,
      physiological traits and stress indices. A set of 131 rice accessions was
      evaluated in two levels namely, non-stress (EC ~ 1.2 dS/m) and saline stress (EC
      ~ 10 dS/m) in hydroponics at seedling stage. Root length and shoot lengths were
      reduced by 52 and 50%, respectively in saline stress compared to non-stress
      conditions. There was a significant correlation between various morphological and
      physiological parameters in non-saline in addition to saline stress as well as
      non-stress. The effect of the increased Na+ concentration in the medium is
      detrimental to root length and shoot length as observed by reduction in root
      length and a concomitant reduction in shoot length. Increased concentration of
      Na+ led to augmented Na+/K+ ratio with increased stress in the medium and
      decreased expression of traits. A significant positive correlation (r=0.60) was
      noticed between stress tolerance index (STI) of root and shoot length. The stress
      susceptibility index (SSI) for root length was expressed significant positive
      correlation with SSI for shoot length (r=0.43). SSI for K+ content was registered
      significant negative correlation with STI for Na+ content (r=-0.43). The three
      accessions namely, IC 545004, IC 545486 and IC 545215 were found to be the best
      performers adjudged on the morphological and physiological criteria in saline
      stress situation. These three rice accessions could be used as a donor parent or
      for genotypic studies in future breeding programs.

PMID- 30183183
TI  - [ROLE OF A NUTRITION SUPPORT TEAM FOR SURGICAL PATIENTS].
AB  - A number of studies have reported that malnutrition is documented in up to 50% of
      hospitalized patients, and malnutrition is closely correlated with the incidence
      of postoperative complications in surgical patients. The concept of a nutrition
      support team (NST) is to use its expertise for the entire spectrum of nutritional
      and metabolic support and to reduce the incidence of complications in
      hospitalized patients. It is widely recommended that the NST include a physician,
      dietitian, nurse, pharmacist, and other medical staff, and the physician should
      play the leading role in maintaining the activity of the NST. The clinical goals
      of the NST are defined as the identification of nutritionally impaired patients,
      making nutritional assessments that can lead to precise dietary therapy, and the
      provision of effective nutritional support. Educating medical students,
      residents, and other clinical staff in clinical nutrition will be an important
      role for NSTs in the near future.

PMID- 30183184
TI  - THE STRUCTURAL CHANGES OF MACROPHAGES INFECTED WITH TICK-BORNE ENCEPHALITIS
      VIRUS.
AB  - Macrophages belong to the innate immune cells and play a key role in the
      pathogenesis of viral infections.The results of ultrastructural study of
      macrophages infected with tick-borne encephalitis virus (TBEV), the
      Flavivirusfamily, pathogens of human infections, affecting the nervous system,
      were presented. With the assistanceof virological methods was found that the TBEV
      are absorbed by macrophages and replication in them. Anultrastructural study has
      shown that the virus enters into the cytoplasm by local destruction of
      plasmalemmaand newly synthesized virus particles exited from the cell by same.
      Simultaneously there is a seal of perinuclearcytoplasm space, where found in a
      large number of ribosomes, microfilaments, ribonucleoprotein fibers and
      viralspecial structure: nucleocapsids, tubular formations and viral layers
      (fabrics). On the surface of last structuresthe newly synthesized virus particles
      were visualized. Thus, the evidence shows that macrophages play a rolein the
      spread of TBEV, being for their the target cell. As active antigen presenting
      cells the macrophages canmodulate the protective response of the body and
      influence on the pathogenesis of tick-borne encephalitis.

PMID- 30183185
TI  - USING OF CELL LINE HepG2 FOR ASSESSMENT OF TOXIC AND METABOLIC EFECTS OF
      ANTIPSYCHOTIC DRUGS.
AB  - In order to study in vitro the toxic and metabolic effects of antipsychotic drugs
      (AP) on the cells of hepaticorigin we used human hepatoblastoma cell line HepG2.
      We cultured HepG2 cells in the presence of two AP ofthe first and second
      generations (haloperidol and olanzapine, respectively) adding them to the culture
      mediumin concentrations that may at the therapeutic use of AP take place in liver
      and other tissues of a high lipid content.In the process of cultivation, we
      detected several products of carbohydrate and lipid metabolism, measuredactivity
      of four hepatocellular enzymes in the culture medium, and estimated cell
      viability/proliferation in theMTS-test. We observed that both AP performed a
      toxic effect on HepG2 cells, the effect was manifested by adecrease in cell
      viability/proliferation and an increase in alkaline phosphatase activity in the
      culture medium.The toxic effect of olanzapine was less pronounced in comparison
      to haloperidol. According to the data from literature,AP upregulate the
      expression of lipogenesis genes in the cells of central nervous system, adipose
      tissueand liver, that might lead to hyperlipidemia. However, we observe in our
      experiments no increase in the levelsof total cholesterol, of cholesterol in
      lipoproteins of high and low density, of triglycerides in the culture
      mediumcontaining haloperidol or olanzapine. That observation may have been due to
      the fact that both AP, which arecationic amphiphiles, are capable to inhibit
      intracellular traffic of lipids. We also found no effects of haloperidoland
      olanzapine on the activity of aspartate aminotransferase and gamma
      glutamyltransferase, while bothAP did reduce the alanine aminotransferase
      activity. Our work proves that HepG2 cells can be helpful as an invitro model to
      obtain new data on metabolic effects of drugs on the cells of hepatic origin and
      to assess the riskof a drug hepatotoxicity in preclinical studies.

PMID- 30183186
TI  - Effect of some phytoconstituents on Fe2+/ascorbate induced lipid peroxidation.
AB  - Transition metals like iron and copper, present inside the body system play a key
      role in the production of reactive oxygen radicals. These free radicals,
      causative agents of lipid peroxidation, not only damage proteins and DNA but also
      gradually changes the cellular membrane structure and ultimately leads to the
      loss of function and integrity. Uncontrolled lipid peroxidation results in
      various age related diseases, malignancy, infective diseases and injuries.
      Antioxidants and other phytochemical constituents present in the various plants
      are known to protect cells from such reactive oxygen species (ROS)-mediated
      damages. Here, we evaluated the effect of certain phytoconstituents present in
      the well-known medicinal plants on ROS scavenging using rat liver homogenate. The
      basal lipid peroxidation was found to be 0.1625+/-0.0095 ngMDA/min/mg protein,
      which got induced to 0.7938+/-0.0478 ngMDA/min/mg protein in the presence of
      Fe2+/ascorbate system. In this context, acteoside, berberine, catechin, 3'5
      dihydroxyflavone7-o-beta-D-galacturonide-4-o-beta-D-glucopyranoside (a flavonoid
      glycoside from cumin), silibin and tetrahydrocurcumin decreased both basal and
      Fe2+/ascorbate induced lipid peroxidation as determined by thiobarbituric acid
      reaction. On the other hand, agnuside, andrographolide, picroside-I, negunoside,
      oleanolic acid, and glycerrihizin, showed enhancement in both basal and induced
      lipid peroxidation. Phytoconstituents which have decreased both basal and
      Fe2+/ascorbate induced lipid peroxidation may act as defensive against the deadly
      effects of ROS, causative agents of lipid peroxidation and other diseases either
      alone or in combination with diet/nutritional supplements.

PMID- 30183187
TI  - FEATURES OF EMBRYONIC DEVELOPMENT OF DIENIA OPHRYDIS (ORCHIDACEAE).
AB  - On example of Dienia ophrydis (J. Koenig) Seidenf (Orchidaceae), we have
      described a new type of embryogenesisof orchids - Dienia-type, which is differs
      from Liparis-type learned earlier in the tribe Malaxideae.Embryogenesis of Dienia
      type is characterized by 1) the development of a single-celled suspensor formedby
      cb-derivative, 2) linear arrangement of germ cells in the tetrad stage, 3) the
      special structure of the embryo inthe stages of tetrads and octants (l, lR, m,
      ci, cb), and 4) the absence of ci and cb cell division. The convergent
      similarityof embryogenesis of Dienia- and Caryophyllaceae-types is proposed. A
      number of specific for D. ophrydisstructures of embryo sac and embryo, including
      "petassum", "fitting" and "suspensor coat" are describedfor the first time.
      Petassum represents remains of the cell walls of pollen tube, and perhaps of
      filamentous apparatusof synergids, plugging the micropyle side of the fertilized
      embryo sac. The only cell of suspensor has aspecific appendix ("fitting"), that
      connects it with the embryo itself. There is "suspensor coat" which surroundsthe
      only suspensor cell, including "fitting", but does not extend to the basal cells
      of the embryo itself.

PMID- 30183188
TI  - DIPOLE-MODIFYING EFFECT OF STYRYLPYRIDINIUM DYES AND FLAVONOIDS ON THE MODEL
      MEMBRANES OF DIFFERENT LIPID COMPOSITIONS.
AB  - The changes in the dipole potential of lipid bilayers (jd) mimicking cell
      membranes induced by the adsorptionof low molecular weight amphiphiles,
      flavonoids (phloretin and quercetin) and styrylpyridinium dyes(RH 421 and RH 237)
      were measured. The method based on the determination of ionophore-induced
      transmembranecurrent was used to evaluate the changes in jd after the addition of
      the modifiers. The characteristicparameters of the Langmuir adsorption isotherm,
      the maximum changes in jd at an infinitely large concentrationof flavonoid and
      its desorption constant, which reflects the affinity of the flavonoid to the
      lipid phase, were determined. The slopes of linear dependencies of increasing in
      jd on the concentration of the styrylpiridiniumdyes in membrane bathing solution
      were defined. It was found that the dipole-modifying effect of phloretin
      dependson the charge of the lipids forming the membranes, while the ability of
      quercetin to reduce jd turned onthe initial hydration of the bilayers. The
      results indicated on the different mechanisms of the decrease in jd atthe
      adsorption of tested flavonoids. It was shown that the changes in jd at the
      incorporation of styrylpyridiniumdyes into bilayers is determined by the
      interaction of the modifiers with the membrane components.

PMID- 30183189
TI  - [MULTIDISCIPLINARY CARE FOR PATIENTS WITH BREAST CANCER].
AB  - Recently, the importance of a team approach to multidisciplinary medical
      treatment and care has been recognized. Patient satisfaction must be the purpose
      of the team approach. With advances in Western scientific methodology, the
      biological approach to breast cancer has been established. However,
      psychological, ethical, economic, and social approaches are also required. Key
      points of the team approach are considered to be the quality of communication
      between the patients and physicians and among medical staff. We believe that
      "caring for people who are ill" leads to a good team approach, resulting in
      patient satisfaction. Additionally, treatment and care should not only occur in a
      hospital as patients live in society. Multidisciplinary care must be extended
      from hospitals to the society at large.

PMID- 30183190
TI  - PATHOMORPHOLOGICAL CHANGES OF THE SKELETAL MUSCLES UNDER FORMATION OF THE
      REPERFUSION SYNDROME.
AB  - Analysis of pathomorphological changes which taking place in muscle tissue after
      reperfusion of previouslyischemic rats limbs allowed to identify three phases of
      the experimental reperfusion syndrome (RS): thefirst or ischemic, the second or
      initial reperfusional, the third or late reperfusional. Morphological changes
      ofthe skeletal muscles in the first stage are characterized by presence of
      dystrophic-necrotic processes and reflectthe compensatory-adaptive reaction of
      the organism to hypoxia. In the third stage one can see the progress
      ofmorphological damages, which develop during the ischemic period against a
      background of exhaustion ofproteinase inhibitors. This indicates the intensity of
      endogenous intoxication of the organism with the productsof disturbed metabolism
      and determines the irreversibility of destructive processes and probability of
      multipleorgan failure. Proceeding from the character of the pathomorphological
      changes and the state of proteinase-inhibitor system one can suppose, that the
      optimal time for medical measures is the first stage and the first hours of the
      second stage (to increase the ischemic tolerance of the skeletal muscles). Taking
      into account the direct relation between the intensity of pathomorphological
      injuries and the imbalance of proteinase-inhibitor system, the usage of
      proteinase-inhibiting medicines for correction of RS-development and reduction of
      the destructive changes during first and second stages is substantiated. When
      reperfusion syndrome lasts for a long time, medical measures become ineffective
      due to the high degree of pathological changes.

PMID- 30183191
TI  - [IMPACT ON PROMOTION OF A MULTIDISCIPLINARY TEAM APPROACH FOR CANCER TREATMENT BY
      THE MEXT PROGRAMS OF "HUMAN RESOURCE DEVELOPMENT PLAN" AND "PROMOTION PLAN FOR
      THE PLATFORM OF HUMAN RESOURCE DEVELOPMENT FOR CANCER"].
AB  - The year 2007 should be remembered as the year when cancer treatment in Japan
      underwent a drastic change. In 2007, the Ministry of Education, Culture, Sports,
      Science and Technology (known as MEXT) announced its "cancer professional
      fostering program," and the Japanese Cancer Act became law. This act facilitated
      the development of a clinical environment in which highly advanced cancer
      treatment is performed. A program for the education of professionals to provide
      cancer care was also designed. It was important to show society that
      professionals who can lead medical teams with distinguished medical skills are
      necessary. Because of the cancer professional fostering program, we were able to
      create a clinical environment to carry out the most advanced cancer treatment and
      to establish education schemes to foster medical specialists. Continuous support
      for the cancer professional fostering program and systems established in relation
      to it is expected.

PMID- 30183192
TI  - [PREFACE TO "WOUND CLOSURE METHODS FOR PREVENTION OF SURGICAL SITE INFECTION AND
      PATHOLOGIC SCARS -- INCISION AND SUTURE METHODS FOR PREVENTION OF SSI,
      HYPERTROPHIC SCARS AND KELOID --"].

PMID- 30183193
TI  - [WOUND CLOSURE METHODS FOR PREVENTION OF SURGICAL SITE INFECTION AND PATHOLOGIC
      SCARS-INCISION AND SUTURE METHODS FOR PREVENTION OF SSI, HYPERTROPHIC SCARS AND
      KELOID-].

PMID- 30183194
TI  - [WHAT WE CAN LEARN FROM A CASE OF MEDICAL MALPRACTICE--MEDICAL NEGLIGENCE CASE
      DISMISSED FOR INITIAL DIAGNOSIS OF BENIGN COLONIC POLYPS (THAT LATER TURNED
      CANCEROUS)].

PMID- 30183195
TI  - [BLUMGART'S TYPE ANASTOMOSES;AN EMERGING TECHNIQUE FOR PANCREATICODUODENECTOMY].

PMID- 30183197
TI  - [MODIFIED BLUMGART SUTURING TECHNIQUE (NAGOYA METHOD) IN PANCREATICOJEJUNOSTOMY].

PMID- 30183196
TI  - [MODIFIED BLUMGART TECHNIQUE OF PANCREATOJEJUNOSTOMY(BLUMGART--DUMPLING METHOD)].

PMID- 30183198
TI  - EMERGENCE OF STEM CELLS. THE DEVELOPMENT OF MULTICELLULARITY AND ITS QUANTITATIVE
      CHARACTERISTICS.
AB  - A new approach to the description of the stem cells emergence in the development
      of multicellular organismshas been proposed based on a formalized description of
      the formation of elementary units of multicellularity- "gistions" by purchasing
      and implementing potentials for implementation of the procedure of divisionof
      functions between the cells. The system of gistions is shown in the form of the
      periodic table, which allowsto predict the structure of the development and to
      measure it. The laws of conservation potentialities in gistionswere suggested,
      explaining the origin of the stem cells. For the quantitative characteristics of
      development theexperimentally determined parameters were described. Using it one
      can not only find a common pool of potentials,but also divide them into separate
      species and, thus, to talk about the structure of the pool and
      characterizechanges in its development.

PMID- 30183199
TI  - INTERACTIONS OF MICROSPORIDIA WITH INFECTED HOST CELL.
AB  - Microsporidia comprise a group of fungi-related obligate intracellular eukaryotic
      pathogens with extremelywide host range: from protists to mammals. Adaptation to
      intracellular parasitism drives these parasites towardssignificant reduction and
      modification of the genome and functional apparatus, which causes extreme
      dependenceon the host cell, as well as sophisticated host-parasite relationships.
      In this review we summarize ourresults and recent literature data about
      microsporidian interactions with the host at the cellular level. The impactsof
      these pathogens to infected cells include induction of hypertrophy, restructuring
      and modification ofthe cytoskeleton and the vesicular transport system of the
      host cells. Microsporidians also able to stimulate themetabolic processes in the
      infected cells and inhibit their defensive reactions. The main tool of the direct
      regulatoryimpact of microsporidia on the host cell apparently is the secretion of
      the special protein effectors capableto interfere to regulatory and signaling
      pathways of the host cell.

PMID- 30183200
TI  - THE STIMULATING EFFECT OF THIENOPYRIMIDINES, THE STRUCTURAL ANALOGS OF ORG 43553,
      ON THE ACTIVITY OF ADENYLYL CYCLASE IN THE TESTES AND ON THE TESTOSTERONE
      PRODUCTION IN MALE RATS
AB  - The regulation of the functional activity of luteinizing hormone (LH) receptor
      can be carried out by using gonadotropins or low-molecular weight agonists of
      this receptor, which, unlike gonadotropins, bind to an allosteric site located in
      the transmembrane channel of the receptor. Thienopyrimidine derivatives, the
      analogs of the compound Org 43553, the greatest interest among the low-molecular
      weight agonists. The aim of the work was synthesis of the novel thienopyrimidine
      derivatives, such as 5-amino-N-(tert-butyl)-4-(3-(2-methoxynicotinamido) phenyl)
      2-(methylthio)thieno [2,3-d]pyrimidine-6-carboxamide (TP-21), 4-(3-(5-amino-6
      (tert-butylcarbamoyl)- 2-) methylthio)thieno[2,3-d] pyrimidine-4
      yl)phenyl)carbamoyl)pyridine 1-ocide (TP-22) and 5-amino-N-(tert-butyl)-4-(3-(2
      chloronicotinamido)-2-(methylthio)thieno[2,3-d] pyrimidine-6-carboxamide (TP-23),
      and the study of their effects in vitro on adenylyl cyclase (AC) activity in
      testicular membranes of rats as well in vivo on the testosterone level in the
      case of their intratesticular and intraperitoneally administration into male
      rats. The compounds TP-21, TP-22 and TP-23 stimulated the basal AS activity in
      rat testicular membranes with the EC50 values, such as 1556, 358 and 372 nM, and
      ranked according to their efficiency in the following order: TP-23 > TP-21 TP-22.
      In the case of combined action of thienopyrimidines (10-4 M) and human chorionic
      gonadotropin (hCG, 10-8 M), the AC stimulating effect of gonadotropin was
      preserved, but at a concentration of 10-4 M, the additivity of AC effects of
      thienopyrimidines and hCG was observed. The TP-21, TP-22 and TP-23, when i. t.
      administered into male rats at a dose of 10 mg/kg, increased the testosterone
      levels, and, 5 h after treatment, the increase of concentration of testosterone
      over its value in the control group was 32.8, 36.4 and 76.9 nM respectively. When
      administered intraparenterally, TP-21 and TP-22 had a little effect on the
      testosterone level, while the compound TP-23 showed significant increase in the
      testosterone level at 1 and 3 h (the increase over control amounted 34.8 and 18.9
      nM). The data obtained indicate a high activity of TP-23, as a stimulator of the
      synthesis and secretion of testosterone, as well as the prospect of development
      on its basis of highly effective agonists of LH receptor.

PMID- 30183201
TI  - Limbic encephalitis associated with antibodies against the alpha-Amino-3-Hydroxy
      5-Methyl-4-Isoxazolepropionic acid receptor: a case report.
AB  - We report a case of a 51-year-old man with limbic encephalitis (LE) associated
      with antibodies against the alpha-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionic
      acid receptor (AMPAR). The patient presented with anterograde memory loss for 2
      months. Cranial magnetic resonance and electroencephalogram were normal. AMPAR
      antibodies were found in blood serum and cerebrospinal fluid. All other test
      results were unremarkable. CT scans found a tumor in the right lobus superior
      pulmonis. A CT-guided needle biopsy was performed and pathological results showed
      small cell lung cancer (SCLC). The patient was diagnosed with LE associated with
      AMPAR antibodies and SCLC. Three months after immunotherapy and tumor removal,
      patient's memory was partially restored. We recommend that AMPAR antibodies
      should be detected in patients with classic LE with or without tumor. Prompt
      treatment of the tumor and immunotherapy are important.

PMID- 30183202
TI  - Diagnosis and treatment of solitary fibrous tumor/hemangiopericytoma of central
      nervous system. Retrospective report of 17 patients and literature review.
AB  - To investigate the diagnosis, treatment and prognosis of solitary fibrous tumor
      (SFT)/ hemangiopericytoma (HPC) of central nervous system (CNS), we
      retrospectively reviewed records of 17 patients who were treated for CNS SFT/HPC
      at the Department of Neurosurgery, China-Japan Union Hospital of Jilin University
      from December 2010 to June 2016, and reevaluated their pathological diagnoses
      according to the 2016 WHO classification of CNS tumors. We then analyzed their
      clinical symptoms, imaging characteristics, treatments and outcomes. Clinical
      manifestations of CNS SFT/HPC were diverse, but mainly included headache,
      increased intracranial pressure, seizures, and focal neurological deficits. In
      MRI, CNS SFT/HPC usually shows heterogeneous signals, and unusual enhancements;
      we saw lobulated shapes in 13 patients and necrotic or cystic changes in 12
      patients. Tumors of all 17 patients were resected surgically; 9 patients also
      received postoperative adjuvant radiotherapy. Mean follow-up time was 21 months
      (range: 2-67 months). The 17 surgeries included 11 total resections, 4 subtotal
      resection, and 2 partial resections. We followed up 12 patients; 9 of the
      patients who received total resections had no disease progression; among the 6
      patients who did not receive total resections, 2 died of tumor recurrence, 1 has
      not shown any disease progression. Thus, extent of resection has an apparently
      crucial influence on prognosis. Postoperative radiotherapy should be chosen
      carefully, based on resection extent and pathologic grade.

PMID- 30183203
TI  - The Comorbidity of Focal Epilepsy and Narcolepsy Type 1 - Two Case Reports.
AB  - The aim of this study is to remind the possibility of co-occurrence of epilepsy
      and narcolepsy. In the first case report, narcolepsy type 1 was diagnosed in 29
      year-old female. After one year of the treatment with modafinil a new episodes of
      automatic behavior appeared. Patient was reevaluated and the diagnosis of focal
      epilepsy with partial complex seizures was established. Patient was treated with
      modafinil and lamotrigine and became seizure-free. In the second case report a 21
      year-old female was referred with a typical history of narcolepsy type 1, but
      also with atypical episodes of gazing and automatic behavior with amnesia for
      these episodes. Narcolepsy type 1 and focal epilepsy was diagnosed. Some clinical
      symptoms of narcolepsy (cataplexy, automatic behavior, episodes of sleep attacks)
      need to be carefully analyzed by EEG and video-EEG not to overlook the epilepsy.

PMID- 30183204
TI  - Rapidly progressive non-alcoholic fatty liver disease due to hypopituitarism.
      Report of 5 cases.
AB  - BACKGROUND: A few reports had revealed the clinical associations between
      hypopituitarism and non-alcoholic fatty liver disease (NAFLD). Further evidences
      were needed. OBJECTIVES: To report 5 cases of young patients with rapidly
      progressive NAFLD in conjunction with hypopituitarism, aiming to detect the
      associations. METHODS: Clinical data of the 5 patients were analyzed
      retrospectively. All had decompensated liver cirrhosis that was finally
      attributed to NAFLD. Hypopituitarism was a result of pituitary stalk interruption
      syndrome in 3 patients and craniopharyngioma in 2. RESULTS: 4 patients were
      overweight (BMI, 24.2 to 28.4kg/m2). All had insulin resistance (HOMA-IR, 4.8 to
      7.2). All suffered from at least one metabolic disorder. All had decompensated
      liver cirrhosis. The average time duration was 6.9 years between the onset of
      abnormal liver function and decompensated liver cirrhosis. Fatty liver could be
      detected in all patients. All had anterior hypopituitarism, and 2 also had
      posterior pituitary dysfunction. The hormone supplements were insufficient.
      CONCLUSION: Hypopituitarism may be a rare cause of rapidly progressive NAFLD.
      Insulin resistance and metabolic disorders caused by multiple hormonal
      deficiencies may contribute to it. Hormone supplement therapy, especially the
      growth hormone supplement, should be given at the early age to prevent the severe
      liver disease.

PMID- 30183205
TI  - Expression of MT1 receptor in patients with gastric adenocarcinoma and its
      relationship with clinicopathological features.
AB  - Gastric cancer accounts 8% of the total cancer cases leading to 10% of total
      cancer deaths worldwide. The indoleamine N-acetyl-5-methoxytryptamine, better
      known as melatonin, is the principal hormone produced by the pineal gland.
      Recently, it has been well documented some anti-cancer roles of melatonin in some
      malignancies as breast and colon cancer; as well as some its protective roles in
      the GI tract that have been known as free radical scavenger, antimitogenic and
      apoptotic properties. According to the anti-cancer effects of melatonin, wide
      distribution of this neurohormone in GI tract and some proposed physiologic and
      pharmacologic roles for this neurohormone and following our previous study which
      has shown expression of MT2 receptor in gastric adenocarcinoma, this study
      initially scheduled to determine the expression of melatonin receptor MT1 in
      tissue samples of adenocarcinoma cancer patients. A total of 10 gastric
      adenocarcinoma patients and 10 normal individuals were examined for MT1 gene
      expression by real-time PCR. Additionally, for screening of different alleles of
      MT1 in our samples, the SSCP-PCR procedure was developed. Our results have shown
      interestingly high expression for MT1 receptor in cancer and marginal cancer
      groups comparing with normal group. Our findings also have shown that a
      remarkable association between MT1 receptor mRNA levels and grade in individuals
      over age 50. PCR-SSCP analysis results showed a variation between individuals
      which may be effective on their gene expression patterns. According to our
      knowledge, for the first time this study evaluated the expression of MT1 receptor
      gene in gastric adenocarcinoma tissues which consistent with our previous study
      but with some difference in comparisons between kind of tissue expression and
      difference in polymorphisms. Moreover, these results show the defending role of
      melatonin in the GI system.

PMID- 30183206
TI  - Integrated analysis of differentially expressed lncRNAs in Medial Temporal Lobe
      Epilepsy.
AB  - BACKGROUND: Medial temporal lobe epilepsy (MTLE) is the most frequent type of
      epilepsy. In recent years, the important roles of lncRNAs in regulating human
      diseases progression had been implicated, including in epilepsy. However,
      comprehensive analysis of differentially expressed lncRNAs in Medial Temporal
      Lobe Epilepsy was still lacking. OBJECTIVES: The aim of this study was to explore
      relevant lncRNAs in MTLE. METHODS: In present study, we analyzed a public dataset
      GSE25453 to identify differentially expressed lncRNAs and mRNAs in the MTLE.
      RESULTS: A total of 16 lncRNAs (C6orf176, NCRNA00259, PRO1768, TTTY11, LOC149620,
      GDEP, LOC400891, HLA-DRB6, TTTY21, TTTY3, NBR2, TTTY1, FAM183B, C15orf51,
      FAM74A3, and MALAT1) were identified. LncRNA co-expression network analysis
      showed these lncRNAs were mainly enriched in regulating transcription,
      inflammatory response, DNA binding, Jak Stat Signaling Pathway, and Mapk
      Signaling Pathway. Meanwhile, lncRNA-mRNA-biological processes networks were also
      performed to evaluate the potential roles of key lncRNAs in MTLE. CONCLUSIONS:
      This study will be useful to explore the potential candidate biomarkers for
      diagnosis, prognosis, and drug targets of MTLE.

PMID- 30183207
TI  - Autonomic dysfunction in patients with irritable bowel syndrome evidenced by
      alterations of salivary alpha-amylase secretion.
AB  - BACKGROUND: Patients with irritable bowel syndrome (IBS) frequently present with
      alterations of autonomic activity, especially higher sympathetic activity.
      Salivary alpha-amylase (sAA) has been implicated as a non-invasive biomarker to
      reflect the sympathetic activity. Thus, the current study aimed to determine if
      alterations of sAA secretion could be addressed in IBS patients. METHODS: We
      recruited twenty-five IBS patients as well as twenty-four age- and sex-matched
      healthy controls (HCs). Basal and stimulated (by gustatory stimulation with
      citric acid) saliva samples were collected from each participant, with respective
      salivary flow rate (SFR) calculated accordingly. Western blotting (WB) was
      applied to determine the sAA amount by introducing human sAA protein of known
      quantity. Then the sAA amount ratio was calculated, as expressed by the
      stimulated sAA amount to basal sAA amount. RESULTS: We observed high variability
      of the basal and stimulated sAA amount in both groups. An apparently higher
      prevalence of psychiatric disorders was detected in the IBS group, which was
      consistent with previous studies. Interestingly, we found elevated basal sAA
      amount in the IBS patients relative to HCs, which implicated higher sympathetic
      activities in IBS population. Moreover, we observed blunted sAA response to the
      gustatory stimulation in the IBS patients, which might be of pathophysiological
      importance for IBS. CONCLUSION: This is the first attempt to associate sAA
      secretion with the pathophysiology of IBS. Our results suggest an autonomic
      dysfunction in IBS patients.

PMID- 30183208
TI  - Effects of alprostadil combined with calcium dobesilate in patients with diabetic
      peripheral neuropathy.
AB  - OBJECTIVE: To observe the clinical curative effects of alprostadil combined with
      calcium dobesilate in type 2 diabetes patients with peripheral neuropathy.
      METHODS: We randomly divided 120 type 2 diabetes patients with diabetic
      peripheral neuropathy into two groups. The treatment group was prescribed
      alprostadil (10 MUg, once daily) and oral calcium dobesilate (0.5 g, 3 times
      daily), and the control group was prescribed alprostadil (10 MUg, once daily) for
      a total treatment duration of 2 weeks. The Michigan Diabetic Neuropathy Score
      (MDNS) and the Michigan Neuropathy Screening Instrument (MNSI) were used to
      evaluate differences between the two groups before and after treatment. RESULTS:
      Following 2 weeks of treatment, the total effective rate in the treatment group
      was significantly better than that of the control group (p<0.05) and the MDNS and
      MNSI scores in the treatment group were significantly lower than those in the
      control group (p<0.05 or p<0.01). CONCLUSION: Combined alprostadil and calcium
      dobesilate treatment for type 2 diabetic peripheral neuropathy showed good
      clinical efficacy and an improved curative effect than single alprostadil
      treatment.

PMID- 30183209
TI  - PHARMACOLOGICAL CORRECTION OF MICROCIRCULATION IN RATS SUFFERED A TRAUMATIC BRAIN
      INJURY.
AB  - We investigated the action of mexicor on functional indices of erythrocytes and
      the structure of myocardialmicrocirculation in rats suffered from traumatic brain
      injury (TBI). At 3, 7 and 12 day after TBI we measuredthe concentration of 2,3
      diphosphoglycerate (2,3-DPG), the degree of erythrocyte aggregation and their
      electrophoreticmobility (EPME) in the blood of rats, and also analyzed sections
      of left ventricular myocardium. Duringthe first day after the TBI we observed a
      decrease in EPME, an increase of erythrocyte aggregation and anincrease of 2,3
      DFG concentration in erythrocytes compared with intact animals. Intraperitoneal
      injection ofmexicor led to an increase of EPME, 2,3-DPG level and reduce an
      aggregation of erythrocytes, which was themost pronounced during the 3-7 day of
      post-traumatic period. Improved functional parameters of erythrocyteswere
      combined with the dynamics of regenerative processes in the heart.
      Intraperitoneal injection of mexicorrestrained architectonic damage of
      microvasculature and cardiomyocytes ultrastructure of the myocardium ofthe left
      ventricle of the heart.

PMID- 30183210
TI  - FINE MORPHOLOGY AND PHYLOGENY OF SPIROPLASMA SP. ISOLATED FROM EYES OF SCRAPIE
      SHEEP.
AB  - Spiroplasma sp. isolated from eyes of sheep with terminal scrapie were reported
      previously to produce intracellularpathology typical for neurodegenerative
      diseases in experimentally infected cell lines (Bastian et al.,2014). These
      isolates have not been yet characterized morphologically or genetically. The
      paper presents light and electron microscopic description, as well as 16SrDNA
      sequence data-based phylogenetic analysis of these isolates grown cell-free. The
      microorganisms were elongated cells of transient helicity up to 10 MUm long, and
      about 100 nm in diameter. Transmission and scanning electron microscopies
      revealed variable morphology, including presence of helical and non-helical
      forms. The 16SrDNA from the novel isolates revealed >99.9% similarityto the
      orthologues from S. chrysopicola and S. syrphidicola, common commensals of
      tabanid and syrphidflies. On phylogenetic trees the scrapie sheep isolates fell
      into the S. chrysopicola-S. syrphidicola-TAAS groupof Diptera-associated species
      suggesting likely route of infection through flies contacting eyes of sheep
      inpastures. The question, whether microorganisms occasionally contaminate eyes of
      sheep with terminal scrapieupon contacts with flies, or spiroplasmas are linked
      with the disease, and tabanids play a role of their obligate orfacultative
      vectors and reservoirs, warrants further investigation.

PMID- 30183211
TI  - INFLUENCE OF MICROSPORIDIAN SPORES ON PHENOLOXIDASE ACTIVITY IN THE HAEMOCYTES OF
      GRYLLUS SPP. (INSECTA: ORTHOPTERA) IN VITRO.
AB  - After incubation with spores of microsporidia Paranosema spp. during 1-2 h, the
      quotes of Gryllus spp.haemolymph cells giving positive reaction in histochemical
      assay for phenoloxidase (PO) activity were significantlylower as compared to the
      control. Spores of microsporidia P. grylli caused 3- and 5.4-fold decrease ofthis
      index in haemocyte monolayers of Gryllus bimaculatus and G. argentinus,
      respectively. The ability ofP. grylli spores to decrease the quote of PO-positive
      cells in G. bimaculatus haemocyte monolayers was strongerwhen monolayers and
      spores had been coincubated for a longer period (2 h) and when the spores used
      weremore fresh (with higher level pf infectivity). Treatment of P. grylli spores
      with antibiotics resulted in diminishingtheir ability to decrease the quote of PO
      positive cells. The highest level of decrease of this index, being28.7-fold, was
      registered when G. bimaculatus haemocytes had been incubated with spores of P.
      locustae, thehighly aggressive parasite which is able to infect orthopteran
      insect hosts belonging to more than 100 speciesand to preserve a high level of
      infectivity for years. Strong correlation has been revealed between infectivity
      ofmicrosporidian spores and their ability to suppress PO system, which is a key
      factor in invertebrate immunity.

PMID- 30183212
TI  - TIP GROWTH OF NEUROSPORA CRASSA IN THE CONDITIONS OF THE RESOURCE DEFICIENCY:
      IMPAIRMENTS IN THE COHERENCE OF ELONGATION, BRANCHING, AND SEPTATION.
AB  - With the aid of intracellular fluorescent probes, peculiarities of elongation,
      branching, septation, and nucleusmorphology have been studied in isolated 400-MUm
      long apical fragments of Neurospora crassa hyphaegrowing for several hours
      without the influx of the nutrient materials from the mycelium. We found that: 1)
      thediameter and growth rate of newly developing branches decreased as compared to
      intact mycelium (from10-20 to 6.5 +/- 0.4 MUm and from 24 +/-   1 to 6.7  +/- 0.5
      MUm/min, respectively), but the initial orientation ofgrowth did not change; 2)
      the branching rhythm was altered; abnormally long internode distances appeared
      (upto 1471 MUm), and the development of some side-branch buds ceased; 3) the
      character of the septation remainedunchanged, as well as the hyphal segment
      length (68  +/- 2 MUm). In hyphae growing for 4.5-5.0 h in isolationfrom the
      whole mycelium, the distance between the tip and the first septum was 210 +/-  15
      MUm, which was comparablewith the respective value in intact mycelium, whereas
      the mean distance between the growth tip and thefirst side branch (492 +/-127
      MUm) and the dispersion of this parameter was considerably higher than in
      intactmycelium. In branches growing in isolation from the intact mycelium for 1.5
      4.5 h, the length of the nucleus-free apical zones near the growth tip (from 5 to
      33 MUm) and the nucleus morphology were similar to the respectivecharacteristics
      known for the N. crassa mycelium. The experimental model described here can be
      usedfor the investigations of molecular and genetic mechanisms regulating the
      interactions between intracellularstructures involved in the tip growth of N.
      crassa.

PMID- 30183213
TI  - HALOPERIDOL MODULATES IONIC TRANSPORT OF CHARA CORALLINA CELLS.
AB  - The effect of the haloperidol (HP), a dopamine D2-receptor antagonist on the
      function of ionic channels ofthe electrically excitable plasma membrane and on
      the cytoskeleton of Chara corallina cells was investigated.Haloperidol was shown
      to block plasmalemmal  Ca2+ channels. Apart from Ca2+ current reduction, the
      presence of HP slowed the kinetics of both activation and inactivation of ionic
      channels. The influence of haloperidol onthe membrane structure was reversible.
      After removal of the neuromodulator, both the amplitude and the kineticsof the
      current development were seen to be completely restored. HP had no effect on Ca2+
      activated chloridechannels. Haloperidol inhibited cytoplasmic motion related to
      microfilamentary complex. Once haloperidolwas removed from cell washing solution,
      cytoplasmic motion was restored. These results let us to assume thatin the
      presence of HP the concentration of free Ca2+ in cytoplasm increases. Also it can
      be assumed that plasmalemmalCa2+-channels of Ch. corallina cells contain binding
      sites similar to dopamine receptors and their antagonists.

PMID- 30183214
TI  - Study of Proteins Based on Surface-Enhanced Raman Spectroscopy (SERS).
AB  - This article outlines the recent progress in surface enhanced Raman spectroscopy
      (SERS) based proteins applications. SERS is a specific Raman spectroscopic
      technique that provides enhanced Raman signals (several orders of magnitude
      greater than normal) for numerous Raman-active analyte molecules adsorbed onto
      rough metal surfaces. SERS is a sensitive, selective, and versatile technique
      that lends to fast data acquisition in actual time. Therefore, SERS has undergone
      rapid development because of its technical advantages in instrumentation, data
      analysis methods and its multiple biological applications. This article
      highlights several representative areas in proteins where SERS could be employed.
      Some of the proteins applications of SERS are more maturely developed, whereas
      others are in their initial stages of development (in laboratories). This article
      discusses the recent developments in SERS based quantitative analysis: directly
      with different substrates (e.g. biomolecules on electrodes, colloidal particles,
      and periodic pattern structure and tip based substrates). Furthermore, SERS based
      techniques are advantageous for obtaining valuable information on protein
      protein, protein-ligand, and protein-drug recognitions via spectral differences
      among molecular bridges. SERS based techniques show considerable promise for
      qualitative and/or quantitative analyses of biological systems.

PMID- 30183222
TI  - Characteristics Analysis of the Thyroid Gland Surface of Normal Human with
      Fourier Transform Infrared (FTIR) Spectra.
AB  - In order to obtain 240 cases of the surface Fourier transform infrared (FTIR)
      spectra of normal human thyroid gland, 120 healthy volunteers were enrolled in
      this study and scanned by using two mid-infrared optical fibers equipped with an
      attenuated total reflectance (ATR) to probe through the skin of two lobes of
      thyroid gland. Then whether there were differences between the surface FTIR
      spectra of the right lobe and that of the left part of the normal human thyroid
      gland was explored by comparing the 35 variables of 12 bands, including peak
      positions, relative intensity ratios and full width at half maximum of FTIR
      spectrums. Also the spectra characteristics of unique absorbent bands that
      represent changes of structure and quantity of variance biochemical substances
      such as nucleic acids, proteins and carbohydrates were illustrated. Results
      indicated that the surface FTIR spectra of the right part and that of the left
      part of the normal human thyroid gland were generally coincided, with
      statistically significant differences in four spectrum parameters, includingF1
      640, P2 920, P1 040 and I2 920/I1 460. A series of data about the 90% normal
      reference range of the unique spectrum parameters in the surface FTIR spectra of
      normal human thyroid gland was gained, and a standard average infrared
      spectrogram which can fully represent the basic features of normal human thyroid
      gland was plotted. The conclusions above could be used as a reference for
      clinical diagnosis of thyroid diseases with FTIR spectroscopy.

PMID- 30183223
TI  - Russell's viper venom induced nephrotoxicity, myotoxicity, and hepatotoxicity
      Neutralization with gold nanoparticle conjugated 2-hydroxy-4-methoxy benzoic acid
      in vivo.
AB  - Snakebite is one of the major neglected tropical diseases and health hazard that
      leads to significant mortality, particularly in rural populations of tropical and
      subtropical countries including India. Antisnake venom serum (ASVS) is the only
      specific treatment against snake envenomation. Available treatment i.e. ASVS have
      many limitations not only low efficiency but also considerable side effects.
      Search for alternative ASVS is a major domain in toxinology research. Targeted
      drug therapy using nanoparticles, an emerging area of nanotechnology, is one such
      alternative. Here, we studied neutralization of ing Russell's viper venom (RVV)
      induced toxicity (nephrotoxicity, myotoxicity, hepatotoxicity) with gold
      nanoparticle-conjugated 2-hydroxy-4-methoxy benzoic acid (GNP-HMBA) in male
      albino mice. We conjugated 2-hydroxy-4-methoxy benzoic acid (HMBA) with gold
      nanoparticle (GNP) by adsorption method, and physico-chemical characterization
      were done by DLS, ZETA potential, FTIR and TEM. Swiss male albino mice were
      divided into four groups viz., sham control, venom control, HMBA treated and GNP
      HMBA treated. Each group had four mice (n=4). RVV was injected in all groups
      except sham control. Groups 3 and 4 had treatment with HMBA and GNP-HMBA,
      respectively. After 24 h, blood and urine were collected. Serum LDH, CK, SGPT,
      SGOT, gamma-GT, ACP, ALP, urea, creatinine and urinary calcium and urinary
      phosphorus were measured. The hydrodynamic diameter of GNP-HMBA was 65-75 nm and
      TEM diameter was 18-28 nm. The serum/urine parameters were found significantly
      increased in venom control group. Degree of RVV neutralization was GNP-HMBA >
      HMBA. Treatment with GNP-HMBA showed partial protection of histopathological
      changes in RVV-induced kidney and liver tissues. It may be concluded that GNP
      HMBA neutralized RVV-induced toxicities (nephrotoxicity, myotoxicity and
      hepatotoxicity) in male albino mice. Further studies are warranted in the
      development of alternative herbal-nanoparticle antidote against snake venom
      induced toxicity.Page(s):  7-14

PMID- 30183224
TI  - Recurrent chromosomal translocations: Is proximity a rule?
AB  - The role of recurrent chromosomal translocations in pathogenesis is well
      characterized in many leukemia subtypes; however, the factors leading to such
      preferential gene fusions are yet to be understood. The proximity of the genetic
      regions is considered important for genetic exchange, and interphase molecular
      cytogenetic methods can be employed to measure the same. The interphase genomic
      location of gene pairs taking part in translocations which are non-randomly
      associated with leukemia subtypes was studied for the extent of proximity by
      measuring relative distance and radial location. The FISH (Fluorescence In Situ
      Hybridization) signals corresponding to gene pairs were scored for relative
      distance and percentage of possible translocation pairs showing proximity which
      was found higher for BCR-ABL, PML-RARA and AML-ETO. The radial position of the
      gene pairs was also recorded to see if there is any preferred location in terms
      of nuclear centre or periphery for translocation partners. The results suggested
      no preferential location of any of the gene pairs in periphery or centre of the
      interphase nucleus, rather random distribution was observed for all the three
      cases. We report here the use of simple interphase FISH method to assess the
      interphase proximity of gene fusion pairs which can be further employed for other
      translocations.

PMID- 30183225
TI  - Effect of Tinospora cordifolia (Guduchi) on the phagocytic and pinocytic activity
      of murine macrophages in vitro.
AB  - Tinospora cordifolia (Guduchi) is a widely used herb in Ayurvedic system of
      medicine known to possess immunomodulatory properties. The present study was
      aimed to study the activation of macrophages after in vitro guduchi treatment.
      The aqueous extract of T. cordifolia was found to enhance phagocytosis and
      pinocytosis in vitro. The rate of pinocytosis by macrophages when measured by
      uptake of horseradish peroxidase was significantly increased after guduchi
      treatment as compared to medium alone. The macrophages demonstrated an increased
      phagocytosis to non-infective microorganisms (heat killed yeast) and live
      infective microorganisms (E. coli) after guduchi treatment. The results
      demonstrate that Guduchi enhances macrophage activation as analyzed by
      cytochemical parameters.

PMID- 30183226
TI  - Neuropharmacological investigations on Actaea acuminata Wall. ex Royle roots.
AB  - Actaea acuminata Wall. ex Royle, synonym of Actaea spicata var. acuminata (Wall.
      ex Royle) H.Hara, commonly called the Himalayan Baneberry ( Ranunculaceae) has
      been investigated for various pharmacological activities, based on its
      traditional claims. Properly identified A. acuminata roots were defatted by
      extracting with petroleum ether. The marc was then extracted in a Soxhlet
      apparatus with methanol. Various pharmacological activities such as antianxiety
      (Elevated plus maze, Hole board and Light/Dark tests), anticonvulsant (Maximum
      electroshock test), antidepressant (Despair swim test), sedative
      (Actophotometer), antistress (Cold swim test), analgesic (Tail immersion test)
      and anti-inflammatory (Carrageenin-induced paw edema model) were evaluated after
      administration of 50, 100 or 200 mg/kg, p.o., doses of methanol extract. The
      methanol extract exhibited significant antianxiety, anticonvulsant,
      antidepressant and antistress activities, and mild sedative activity at a dose of
      200 mg/kg. It was found to be devoid of analgesic and anti-inflammatory
      activities. Preliminary phytochemical screening of methanol extract showed the
      presence of alkaloids and polyphenols. Thus, CNS activities of the plant may be
      attributed to these groups of phytoconstituents.

PMID- 30183227
TI  - Characterization of phytotoxin producing Alternaria species isolatedfrom sesame
      leavesand their toxicity.
AB  - Sesame (Sesamum indicum L.), is an important oilseed crop in the tropics and
      subtropics, referred as "Queen of Oilseeds" owing to its high cooking quality and
      medicinal value. Sesame production, particularly in India, has been declining
      since last decade and 'Leaf blight' caused by Alternaria spp. is reported to
      cause yield loss up to 30-40%. Here, we investigated the fungal toxin produced by
      Alternaria and its pathogenicity. A total of 164 Alternaria strainswere isolated
      on potato dextrose agar media from the infected sesame leaves showing circular
      concentric rings with dark brown spots symptoms. All the isolates were screened
      for cultural and morphological characters. Colour of the fungus was grey to dark
      brown, formed smooth, raised, fluffy, and regular to irregular margins. Among 164
      isolates, 43 isolates were moderately growing and 121 were fast in growth. The
      DNA of the isolate was amplified with ITS primers and sequence of BLAST results
      confirmed seven different species of Alternaria of NCBI database. Further,
      toxigenic potentiality of the isolates was tested with dilutions of culture
      filtrate (1:1 to 1:5) on sesame leaves. Among 164 isolates, 23 showed
      toxigenicity, varied from highly toxigenic to least toxigenic. Pathogenicity of
      the isolates showed that they were highly virulent to less virulent when tested
      by the detached leaf method. Based on the toxigenicity, the toxin was partially
      purified and brown coloured paste was recovered. Chemistry of the toxin was
      confirmed based on the IR, UV, NMR and mass spectra analyses, and it resembled
      the structure of alternariol mono methyl ether and altenuene which are mycotoxins
      in nature. Further, bioassay of toxin was carried out at different concentrations
      (50 to 2000 ppm) on seeds and seedlings of sesame. Maximum inhibition of seed
      germination of 81.1% was observed at 2000 ppm and the least was 6.67% at 50 ppm.
      With the increase in the concentration of toxin, the manifestation of the symptom
      was conspicuous and quick such as marginal, veinal necrosis, drooping and
      yellowing with lesion formation. From the present study, it is found that the
      species of Alternaria are responsible for the cause of blight disease symptoms
      and the toxicity of toxin produced by the pathogen was very high. The Alternaria
      toxin could inhibit the growth of the plant as well as seed germination rate.

PMID- 30183228
TI  - Effect of discrete (individual) and mixed (bulk) genomic DNA on genetic diversity
      estimates and population structure in Teak (Tectona grandis L. f.).
AB  - Teak (Tectona grandis L.f.), a paragon timber tree of tropical deciduous forests
      of Central and Peninsular India, is highly prized for its wood colour, decorative
      grains, durability and lightness. An experiment was carried out to compare the
      genetic variation detected and genetic relationships inferred in five teak
      populations via 10 genomic DNA samples per population each of either single seed
      or bulk of 3- or 5- seeds with the help of ISSR markers. The genomic DNA of
      single seed exhibited higher number of polymorphic loci, per cent polymorphism,
      nei's genetic diversity and shannon Information Index than the bulk genomic DNA
      of 3- or 5- seeds. The bulking of genomic DNA of 3- and 5- seeds using Nei's
      genetic distance coefficient revealed similar genetic relationships, which were
      at variance with those in single seed treatment. Mantel's correlation test among
      the genetic distance matrices of single seed sampling, 3-seed bulk and 5-seed
      bulk sampling also confirmed the trend. Since the bulking of genomic DNA did not
      generate compatible estimates of diversity parameters and genetic relationship of
      five populations from its single seed sampling, we recommend strict guarding of
      identities of genotypes within the collected samples for obtaining precise
      estimates and drawing accurate conclusions about the genetic diversity and
      clustering of populations.

PMID- 30183229
TI  - Effect of Delonix regia (Boj. Ex Hook.) Raf. stem bark extract against
      experimentally induced ulcers in rats.
AB  - Delonix regia, commonly called Flame Tree or Flamboyant (locally, Gul Mohor) is a
      common tree traditionally used to treat various diseases like gastric problems,
      body pain, rheumatic pains of joints and wound healing. Here, we carried out
      biological profiling of Delonix regia as antiulcer agent. Antiulcer activity of
      the ethanol extract from stem bark was evaluated on pylorus ligation and
      indomethacin induced ulcer in Wistar albino rats. Ethanol extract from stem bark
      of D.regia was administered at the doses 100, 200 and 400 mg/kg/day, p.o. for 7
      days. Ulcer index, gastric pH, volume, free acidity, total acidity, total
      carbohydrate (TC), protein (P), mucin content (TC/P) and gastric mucus were
      evaluated in pylorus ligation model, while ulcer index, malondialdehyde, GSH,
      PGE2, and gastric mucus were estimated in the indomethacin induced ulcer model.
      Ex vivo assay for the activity of H+/K+-ATPase was also done. The results showed
      significant inhibition on H+/K+-ATPase in a dose dependent manner and
      comparableto their respective positive control group of rats demonstrating that
      ethanol extract of stem bark of Delonix regia possesses significant antiulcer
      properties.

PMID- 30183230
TI  - Therapeutic potentials of herbal drugs for Alzheimer's disease-An overview.
AB  - Alzheimer's disease (AD) is a well known progressive neurodegenerative disorder
      having complex pathophysiology. Currently, drugs that are used symptomatically in
      the treatment of AD include acetylcholinesterase inhibitors (AChEIs)
      (rivastigmine, galantamine, donepezil) and N-methyl D-aspartate (NMDA) receptor
      antagonist (memantine). Limited bioavailability of these drugs stresses
      continuity of search for novel therapeutics for this slow growing but complex
      disease. Herbal drugs are being used to treat memory related problems, including
      Alzheimer's from time immemorial. Both preclinical and clinical studies
      demonstrated the therapeutic potential of herbal drugs for the prevention of AD.
      Herbal drugs have been shown to be effective against Alzheimer's possibly due to
      their pleiotropic and multifaceted action that includes antioxidants, anti
      inflammatory and neuroprotective action. This review highlights the therapeutic
      potential of herbal drugs for the treatment of AD.

PMID- 30183231
TI  - Mitochondrial membrane-bound activity of arginase is independent of nitrogen
      excretion pattern in ureogenic and non-ureogenic vertebrates.
AB  - Arginase, that regulates metabolism of arginine, is widely distributed in
      organisms. The two major isoforms, cytosolic Arginase-I, and mitochondrial
      Arginase-II have been characterized well. However, reports also suggest another
      mitochondrial membrane-bound arginase which is extracted by washing the
      mitochondria with KCl. Here, we studied this mitochondrial membrane-bound
      arginase among vertebrates. Our observations support that arginase activity is
      predominant in cytosol which is designated as Arginase-I. The mitochondrial
      membrane-bound Arginase (mbArg) which resembles Arginase-II seems independent of
      nitrogen excretion pattern because of its presence both in ureogenic and non
      ureogenic vertebrates.

PMID- 30183233
TI  - Cacluated Decisions: TASH (Trauma Associated Severe Hemorrhage) Score
AB  - The TASH Score predicts the need for massive transfusion based on clinical and
      laboratory data.

PMID- 30183232
TI  - Isolation, proliferation, characterization and in vivo osteogenic potential of
      bone-marrow derived mesenchymal stem cells (rBMSC) in rabbit model.
AB  - Information on isolation, characterization of rabbit MSC and its evaluation in
      critical bone defect (CSD) is scarcely available. Here, we attempted to isolate,
      proliferate, differentiate, characterize and evaluate the in vivo osteogenic
      potential of bone marrow derived mesenchymal stem cells (BMSCs) collected from
      New Zealand White rabbits. They were isolated and proliferated in antibiotic
      supplemented DMEM (Dulbecco's Modified Eagle's media). Osteogenic differentiation
      of rabbit bone marrow derived mesenchymal stem cells (rBMSCs) was induced by
      osteogenic supplements and evaluated by alizarin red staining and alkaline
      phosphatase activity assay and characterized by specific CD surface antigen
      markers through FACS (Fluorescent activated cell shorting) and RT-PCR. Day '0'
      cells were round/oval and floating, and on day 3-5, cell attachment with
      spindle/polygonal/star morphology was seen. On subsequent passages, they assumed
      uniform spindle shaped morphology. After culturing in respective differentiation
      media rBMSCs showed increased alkaline phosphatase activity, intense alizarin red
      staining, blue staining for Alcian blue and deep red colour on oil red O staining
      supporting the osteogenic, chondrogenic and adipogenic differentiation ability.
      In vivo osteogenic potential of rBMSCs was evaluated in a 30 mm critical sized
      defect of rabbit radius. The cellular morphology of plastic adherent cells was
      seen as single cell form in P0 and in P1, P2 and P3, as elongated/spindle-shape
      in clusters. The rBMSCs were positive for CD44, CD73 and CD105 and negative for
      CD34 and CD45 and could differentiate to osteogenic cells in osteogenic induction
      media. The in vivo experiments in rabbit CSD model confirmed that rBMSCs promote
      faster healing of critical size defects. Hence, we may suggest that rBMSCs are
      suitable for bone formation in fracture healing and non-union.

PMID- 30183234
TI  - Calculated Decisions: Focused Assessment With Sonography for Trauma (FAST)
AB  - Focused Assessment with Sonography for Trauma (FAST) predicts the presence of
      pericardial or intra-abdominal injury after penetrating or blunt trauma.

PMID- 30183235
TI  - Anti-inflammatory activity of cyclo-oxygenase2 inhibitory anionic protein
      fraction from Lamellidens marginalis (Lamarck).
AB  - Aqueous extract of freshwater mussel, Lamellidens marginalis is known to possess
      potent antioxidant and anti-inflammatory activity. Here, we have made an attempt
      to purify anti-inflammatory protein from Lamellidens marginalis extract (LME).
      Aqueous LME was prepared, and total protein was precipitated by 60% ammonium
      sulfate followed by purification through ion exchange chromatography. Isolated
      fractions were studied for anti-inflammatory activity in in vitro and in vivo
      experimental models. Active fractions were characterized by SDS PAGE and HPLC.
      Protein recovered from ammonium sulfate precipitation showed four distinct peaks
      in diethyl-aminoethyl cellulose ion exchange chromatography when eluted with
      stepwise salt gradient. Protein fraction eluted in 0.5 M sodium chloride solution
      showed maximum specific activity and anti-inflammatory activity in acute model
      and adjuvant induced chronic inflammation model. This fraction also showed cyclo
      oxygenase 2 (COX2) enzyme inhibitory activity in in-vitro system. In SDS-PAGE 0.5
      M NaCl fraction showed multiple bands after Coomassie brilliant blue staining and
      three distinct peaks in HPLC. In this study, we identified an anti-inflammatory
      protein fraction with high anionic property which could be attributed to
      inhibition of COX2 enzyme activity.

PMID- 30183236
TI  - Topical application of Salvia officinalis hydroethanolic leaf extract improves
      wound healing process.
AB  - Salvia officinalis L. (common sage) is a popular herb in the mint family,
      Lamiaceae. To our knowledge, literature regarding the wound healing properties
      hydroethanolic extract of Salvia officinalis is scarce. Here, we tried to
      evaluate the in vitro antioxidant properties and in vivo wound healing activity
      of the hydroethanolic extract of S. officinalis. About 105 healthy Wistar rats
      were inflicted with wound by excision and incisionand were randomly divided into
      five experimental groups: Group I, as control; Group II, received placebo; groups
      III-V treated with 1, 3 and 5% S. officinalis hydroethanolic leaf extract,
      respectively. Thehydroethanolic leaf extract of Salvia officinalis showed the
      highest total flavonoid and phenolic content and antioxidant capacity. Topical
      application of S. officinalis extract, especially higher dose,significantly (P
      <0.05) increased the percentage of wound contraction, a period of re
      epithelialization, breaking strength ratio and upregulated hydroxyproline content
      versus control group. Additionally, S. officinalis significantly (P <0.05)
      increased the new vessel formation and Fibroblast distribution. Our results
      showed that S. officinalis,especially S. officinalis 5%,were significantly
      promoting wound healing effect and can be considered as an appropriate compound
      for clinical application in wound care.

PMID- 30183237
TI  - Calculated Decisions: Blast Lung Injury Severity Score
AB  - The Blast Lung Injury Severity Score stratifies primary blast lung injuries into
      3 categories to guide ventilator treatment.

PMID- 30183238
TI  - Calculated Decisions: Bastion Classification of Lower Limb Blast Injuries
AB  - The Bastion Classification criteria stratify explosionrelated lower limb injuries
      into 5 categories to guide treatment.

PMID- 30183239
TI  - Calculated decisions: Glasgow Coma Scale
AB  - The Glasgow Coma Scale (GCS) estimates coma severity based on eye, verbal, and
      motor criteria.

PMID- 30183240
TI  - Calculated Decisions: Ottawa Ankle Rule
AB  - The Ottawa Ankle Rule shows the areas of tenderness to be evaluated in ankle
      trauma patients to determine the need for imaging.

PMID- 30183241
TI  - Calculated Decisions: Ottawa Knee Rule
AB  - The Ottawa Knee Rule describes criteria for knee trauma patients who are at low
      risk for clinically significant fracture and do not warrant knee imaging.

PMID- 30183242
TI  - Ultrafast Achievement of a Superhydrophilic/Hydrophobic Janus Foam by Femtosecond
      Laser Ablation for Directional Water Transport and Efficient Fog Harvesting.
AB  - Water scarcity is a serious global challenge, especially in arid and desert
      regions. Functional devices for directional water transport and fog collection
      have received increasing attention. Existing methods and technologies suffer from
      low fog-collecting efficiencies, complicated fabrication processes, and high
      fabrication costs. Herein, we report a simple and low-cost method to rapidly
      fabricate nanoparticle-covered microstructures on one side of a copper foam
      surface, using one-step femtosecond laser direct writing technology, which
      enormously improved processing efficiency. The resulting foam exhibits
      superhydrophilic/hydrophobic Janus properties. The foam allows water droplets to
      pass from the hydrophobic side to the superhydrophilic side, but not in the
      opposite direction. The Janus foam can therefore be used for harvesting water in
      fog environments, and the maximum water-collecting efficiency is 3.7 g cm-2 h-1,
      which is much better than existing data. The Janus foam exhibits excellent
      stability during abrasion and hydraulic wash tests. This water-collecting design
      may provide an efficient route for overcoming future water shortages.

PMID- 30183243
TI  - Mesoporous ZnMn2O4 Microtubules Derived from a Biomorphic Strategy for High
      Performance Lithium/Sodium Ion Batteries.
AB  - ZnMn2O4 microtubules (ZMO-MTs) with a mesoporous structure are fabricated by a
      novel yet effective biomorphic approach employing cotton fiber as a biotemplate.
      The fabricated ZMO-MT has approximately an inner diameter of 8.5 MUm and wall
      thickness of 1.5 MUm. Further, the sample of ZMO-MT displays a large specific
      surface area of 48.5 m2 g-1. When evaluated as a negative material for Li-ion
      batteries, ZMO-MT demonstrates an improved cyclic performance with discharge
      capacities of 750.4 and 535.2 mA h g-1 after 300 cycles, under current densities
      of 200 and 500 mA g-1, respectively. Meanwhile, ZMO-MT exhibits superior rate
      performances with high reversible discharge capacities of 614.7 and 465.2 mA h g
      1 under high rates of 1000 and 2000 mA g-1, respectively. In sodium ion batteries
      applications, ZMO-MT delivers excellent high discharge capacities of 102 and 71.4
      mA h g-1 after 300 cycles under 100 and 200 mA g-1, respectively. An excellent
      rate capability of 58.2 mA h g-1 under the current density of 2000 mA g-1 can
      also be achieved. The promising cycling performance and rate capability could be
      benefited from the unique one-dimensional mesoporous microtubular architecture of
      ZMO-MT, which offers a large electrolyte/electrode accessible contact area and
      short diffusion distance for both of ions and electrons, buffering the volume
      variation originated from the repeated ion intercalation/deintercalation
      processes.

PMID- 30183244
TI  - Liquid-Infused Surfaces on Electrosurgical Instruments with Exceptional
      Antiadhesion and Low-Damage Performances.
AB  - Electrosurgery based on electrosurgical instruments plays an important role in
      clinical surgery owing to its advantages of ease of operation, low damage, and
      less pain to the patient. But soft tissue adhesion on electrosurgical instruments
      is still a major obstacle to improve the operation efficiency and achieve a
      better surgical result, regardless of so many developed methods to enhance the
      antiadhesion performance. In this paper, we successfully demonstrated that liquid
      infused surfaces (LISs) can significantly improve the antiadhesion performance of
      electrosurgical instruments. We developed a microcontact printing method to
      assist the structure fabrication on the small instrument tip to prepare a firmly
      liquid-held surface. Soft tissue cutting experiments showed that LIS could not
      only significantly reduce the adhesion force between the tissue and the
      instrument tip but also lead to a much smaller charring wound. The underlying
      mechanism was discussed, and further experiments concluded that LIS have a better
      duration capability. Our study provides a new insight into the antiadhesion
      design for electrosurgical instruments.

PMID- 30183245
TI  - Pentacene/TiO2 Anatase Hybrid Interface Study by Scanning Probe Microscopy and
      First Principles Calculations.
AB  - The understanding and control of the buried interface between functional
      materials in optoelectronic devices is key to improving device performance. We
      combined atomic resolution scanning probe microscopy with first-principles
      calculations to characterize the technologically relevant organic/inorganic
      interface structure between pentacene molecules and the TiO2 anatase (101)
      surface. A multipass atomic force microscopy imaging technique overcomes the
      technical challenge of imaging simultaneously the corrugated anatase substrate,
      molecular adsorbates, monolayers, and bilayers at the same level of detail.
      Submolecular resolution images revealed the orientation of the adsorbates with
      respect to the substrate and allowed direct insights into interface formation.
      Pentacene molecules were found to physisorb parallel to the anatase substrate in
      the first contact layer, passivating the surface and promoting bulk-like growth
      in further organic layers. While molecular electronic states were not
      significantly hybridized by the substrate, simulations predicted localized
      pathways for molecule-surface charge injection. The localized states were
      associated with the molecular lowest unoccupied molecular orbital inside the
      oxide conduction band, pointing to efficient transfer of photo-induced electron
      charge carriers across this interface in prospective photovoltaic devices. In
      uncovering the atomic arrangement and favorable electronic properties of the
      pentacene/anatase interface, our findings testify to the maturity and analytic
      power of our methodology in further studies of organic/inorganic interfaces.

PMID- 30183246
TI  - Competition of Carrier Separation and Recombination for an Optimized Electrode
      Configuration for Flexible Thin-Film Solar Cells.
AB  - The inhibition of the rapid recombination of photochemical charges at
      heterointerfaces and the promotion of transfer and extraction are central to
      photoelectric conversion in solar cells. With the use of Cu4Bi4S9 nanoribbons
      graphene sheets (CBS-GSs) as a hybrid photosensitive layer and the growth of ZnO
      nanowires on Zn2SnO4 nanowires (ZTO-ZnO) for the electron transfer layer, a
      flexible solar cell ZTO-ZnO/CBS-GSs was prepared on a stainless steel mesh. In
      this study, time-resolved fluorescence spectroscopy (TFS) and transient surface
      photovoltage (TPV) were used to describe the transition and transport process for
      the photogenerated carriers. With a high fill factor (0.76) and improved electron
      mobility for the ZTO-ZnO nanostructure, a high photoelectric conversion
      efficiency of 11.6% was obtained, which was evidently higher than that of a
      ZTO/CBS-GSs cell (9.2%) and a ZnO nanoparticles/CBS-GSs cell (3.9%). The
      efficient dissociation of photogenerated carriers at CBS-GSs interfaces, rapid
      transfer of free electrons in the ZTO-ZnO system, and fast extraction of holes
      from the selective NiO layer with an optimized architecture led to a superior
      performance. The charge recombination at the interface can be determined by
      electrochemical impedance spectroscopy (EIS). Active exploration via inevitable
      competition between charge separation and recombination (TFS, TPV, EIS, etc.) can
      provide insights into the entire dynamic process and a separation mechanism for
      photoinduced carriers, which can also promote the application of flexible thin
      film solar cells.

PMID- 30183247
TI  - Decoration of Cisplatin on 2D Metal-Organic Frameworks for Enhanced Anticancer
      Effects through Highly Increased Reactive Oxygen Species Generation.
AB  - Herein, a biocompatible 2D metal-organic frameworks (Cu-TCPP(Fe)) based on
      TCPP(M) (TCPP = tetrakis (4-carboxyphenyl) porphyrin, M = Fe) and copper ion were
      synthesized as a novel drug carrier. Sequentially, the cisplatin was loaded on
      the merge of carboxyl-rich Cu-TCPP(Fe) through forming favorable carboxyl-drug
      interactions. The prepared Pt/Cu-TCPP(Fe) showed highly enhanced cytotoxicity
      than that of free cisplatin in human pulmonary carcinoma A549 cells, whereas
      inverse inhibitory effects were observed in human normal BEAS-2B cells. Further,
      the mechanism of action about the desirable results was also elaborated. Our
      study highlighted the potential synergies between the nanocarrier and the
      anticancer drugs.

PMID- 30183248
TI  - Hole-Injection Layer-Free Perovskite Light-Emitting Diodes.
AB  - In this study, a dual-source vapor evaporation method was employed to fabricate
      the high-quality CsPbBr3 thin films with a good crystalline and high surface
      coverage. Temperature-dependent and excitation power-dependent photoluminescence
      measurements were performed to study the optical properties of the CsPbBr3
      material. Further, based on the experimental data, the temperature sensitivity
      coefficient of band gap and exciton binding energy were estimated. More
      importantly, for the first time, we designed and prepared a hole-injection layer
      free perovskite light-emitting diode (LED) based on the Au/MgO/CsPbBr3/n-MgZnO/n+
      GaN structure, producing an intense green emission (~538 nm) with a high purity.
      Besides, the device demonstrated a high luminance of 5025 cd/m2, an external
      quantum efficiency of 1.46%, a current efficiency of 1.92 cd/A, and a power
      efficiency of 1.76 lm/W. We studied in detail the current-voltage and
      electroluminescence properties of the prepared device and proposed the hole
      generation models and the carrier transport/recombination mechanisms to make
      these interesting characteristics certain. The results obtained would provide a
      new and effective strategy for the design and preparation of perovskite LEDs.

PMID- 30183249
TI  - Hybrid Characteristics of MoS2 Monolayer with Organic Semiconducting Tetracene
      and Application to Anti-Ambipolar Field Effect Transistor.
AB  - An n-type MoS2 monolayer grown by chemical vapor deposition method was partially
      hybridized with an organic semiconducting p-type tetracene thin film. The
      photoluminescence (PL) intensity in the hybrid region of the MoS2/tetracene is
      clearly lower than that of pristine tetracene because of the charge-transfer
      effect, which was confirmed by the decrease in exciton lifetimes. Decrease in the
      temperature led to blue-shift in the PL peak position of MoS2 layers and,
      consequently, the PL intensities of both tetracene and MoS2 considerably
      increased owing to the decrease in phonon interaction. The PL spectra of bound
      excitons in the hybrid region were clearly observed at low temperatures,
      indicating the formation of trap states. The lateral-type n-p heterojunction
      field-effect transistors (FETs) using the MoS2/tetracene hybrid as an active
      layer showed gate-tunable rectification I- V and anti-ambipolar field-effect
      characteristics with hysteresis effect. The charge transport characteristics
      across the n-p heterojunction of the hybrid region of the FET can be explained in
      terms of the Shockley-Read-Hall trap-intermediated tunneling and Langevin
      recombination mechanisms. To improve the performance of MoS2/tetracene-based FET,
      a dielectric hexagonal boron nitride (h-BN) thin layer was inserted between the
      SiO2 surface and the active MoS2 layer. We observed the decrease in the
      hysteresis effect and threshold voltage of the h-BN/MoS2/tetracene-based FETs due
      to the decrease in the number of traps at the interface. The performance of h
      BN/MoS2/tetracene FET device was also enhanced after the annealing process.

PMID- 30183250
TI  - Activation of the NLRP3 Inflammasome by Hyaboron, a New Asymmetric Boron
      Containing Macrodiolide from the Myxobacterium Hyalangium minutum.
AB  - A Natural Compound Library containing myxobacterial secondary metabolites was
      screened in murine macrophages for novel activators of IL-1beta maturation and
      secretion. The most potent of three hits in total was a so far undescribed
      metabolite, which was identified from the myxobacterium Hyalangium minutum strain
      Hym3. While the planar structure of 1 was elucidated by high resolution mass
      spectrometry and NMR data yielding an asymmetric boron containing a macrodiolide
      core structure, its relative stereochemistry of all 20 stereocenters of the 42
      membered ring was assigned by rotating frame Overhause effect spectroscopy
      correlations, 1H,1H, and 1H,13C coupling constants, and by comparison of 13C
      chemical shifts to those of the structurally related metabolites tartrolon B-D.
      The absolute stereochemistry was subsequently assigned by Mosher's and Marfey's
      methods. Further functional studies revealed that hyaboron and other boronated
      natural compounds resulted in NLRP3 inflammasome dependent IL-1beta maturation,
      which is most likely due to their ability to act as potassium ionophores.
      Moreover, besides its inflammasome-stimulatory activity in human and mouse cells,
      hyaboron (1) showed additional diverse biological activities, including
      antibacterial and antiparasitic effects.

PMID- 30183251
TI  - Alpha-Synuclein Nitration and Its Implications in Parkinson's Disease.
AB  - Parkinson's disease is pathologically characterized by the degeneration of
      dopaminergic neurons in the substantia nigra and the accumulation of neuronal
      cytoplasmic inclusions known as Lewy bodies, which are primarily composed of
      alpha-synuclein. Post-translational modifications of alpha-synuclein induced by
      nitrative stress have been linked to neurodegeneration. Here, we review the
      concept of alpha-synuclein nitration and its biological consequences. We also
      discuss the pathological roles of nitrated alpha-synuclein and their potential
      clinical implications in Parkinson's disease.

PMID- 30183252
TI  - Mechanosensation-Active Matrix Based on Direct-Contact Tribotronic Planar
      Graphene Transistor Array.
AB  - Mechanosensitive electronics aims at replicating the multifunctions of human skin
      to realize quantitative conversion of external stimuli into electronic signals
      and provide corresponding feedback instructions. Here, we report a
      mechanosensation-active matrix based on a direct-contact tribotronic planar
      graphene transistor array. Ion gel is utilized as both the dielectric in the
      graphene transistor and the friction layer for triboelectric potential coupling
      to achieve highly efficient gating and sensation properties. Different contact
      distances between the ion gel and other friction materials produce different
      triboelectric potentials, which are directly coupled to the graphene channel and
      lead to different output signals through modulating the Fermi level of graphene.
      Based on this mechanism, the tribotronic graphene transistor is capable of
      sensing approaching distances, recognizing the category of different materials,
      and even distinguishing voices. It possesses excellent sensing properties,
      including high sensitivity (0.16 mm-1), fast response time (~15 ms), and
      excellent durability (over 1000 cycles). Furthermore, the fabricated
      mechanosensation-active matrix is demonstrated to sense spatial contact distances
      and visualize a 2D color mapping of the target object. The tribotronic active
      matrix with ion gel as dielectric/friction layer provides a route for efficient
      and low-power-consuming mechanosensation in a noninvasive fashion. It is of great
      significance in multifunction sensory systems, wearable human-machine interactive
      interfaces, artificial electronic skin, and future telemedicine for patient
      surveillance.

PMID- 30183253
TI  - Enhanced Transdermal Drug Delivery by Transfersome-Embedded Oligopeptide Hydrogel
      for Topical Chemotherapy of Melanoma.
AB  - Topical administration of anticancer drugs provides a potential chemotherapeutic
      modality with high patient compliance for cutaneous melanoma. However, the drug
      delivery efficiency is highly limited by physiological barriers from the skin to
      the tumor, which cannot acquire desired therapeutic efficacy. Herein, we propose
      a paintable oligopeptide hydrogel containing paclitaxel (PTX)-encapsulated cell
      penetrating-peptide (CPP)-modified transfersomes (PTX-CTs) to enhance transdermal
      PTX delivery for topical melanoma treatment. After being plastered on the skin
      above the melanoma tumor, the PTX-CTs-embedded hydrogel (PTX-CTs/Gel) as a patch
      provided prolonged retention capacity of the PTX-CTs on the skin. The PTX-CTs
      with superior deformability could efficiently squeeze through the channels in the
      stratum coreum, and the surfactant components improved the fluidity of the lipid
      molecules in the stratum corneum to further enhance the skin permeation.
      Moreover, the CPP modification rendered the PTX-CT-enhanced penetration in the
      skin and tumor stroma as well as efficient transportation in the tumor cells. The
      PTX-CTs were shown to effectively slow the tumor growth in combination with the
      systemic chemotherapy using Taxol, the commercial PTX formulation on the
      xenograft B10F16 melanoma mouse model.

PMID- 30183254
TI  - In Situ Drug Delivery to Breast Cancer-Associated Extracellular Matrix.
AB  - The extracellular matrix (ECM) contributes to tumor progression through changes
      induced by tumor and stromal cell signals that promote increased ECM density and
      stiffness. The increase in ECM stiffness is known to promote tumor cell invasion
      into surrounding tissues and metastasis. In addition, this scar-like ECM creates
      a protective barrier around the tumor that reduces the effectiveness of innate
      and synthetic antitumor agents. Herein, clinically approved breast cancer
      therapies as well as novel experimental approaches that target the ECM are
      discussed, including in situ hydrogel drug delivery systems, an emerging
      technology the delivers toxic chemotherapeutics, gene-silencing microRNAs, and
      tumor suppressing immune cells directly inside the tumor. Intratumor delivery of
      therapeutic agents has the potential to drastically reduce systemic side effects
      experienced by the patient and increase the efficacy of these agents. This review
      also describes the opposing effects of ECM degradation on tumor progression,
      where some studies report improved drug delivery and delayed cancer progression
      and others report enhanced metastasis and decreased patient survival. Given the
      recent increase in ECM-targeting drugs entering preclinical and clinical trials,
      understanding and addressing the factors that impact the effect of the ECM on
      tumor progression is imperative for the sake of patient safety and survival
      outcome.

PMID- 30183255
TI  - Controlling Interlayer Spacing of Graphene Oxide Membranes by External Pressure
      Regulation.
AB  - Graphene oxide (GO) membranes have been attracting numerous attention due to
      their impressive performance in various applications, especially in water
      purification. However, because the swelling in water and polar organic solvents
      causes the increase of interlayer channels, GO membranes usually possess inferior
      rejection for subnanometer-sized molecules. How to control the transport channels
      of GO membranes at angstrom level is a significantly scientific and practical
      issue. Herein, a concept of external pressure regulation (EPR) is reported for
      restraining GO swelling and controlling its interlayer spacing precisely. Since
      anisotropic GO films only swell at vertical direction, the interlayer channels
      can be manipulated by externally unidirectional reverse force. Based on this
      concept, an EPR system with GO membranes is designed for water desalination by
      adjusting the external pressure that has high resolution. In cross-flow
      filtration, the compressed GO membranes show high KCl, NaCl, and CaCl2 rejections
      of 94%, 97%, and 98%, respectively, accompanied by large water permeance up to 25
      L m-2 h-1 under low feed pressure of 2 bar, despite the fact that the semi-free
      spatial swelling of ultrathin GO layer above the substrate pores can deteriorate
      salt rejection. Our work provides a straightforward physical strategy to adjust
      the interlayer spacing of the membranes fabricated by two-dimensional nanosheets
      for achieving desired filtration capacity.

PMID- 30183256
TI  - Near-IR Fluorescent Tracer for Glucose-Uptake Monitoring in Live Cells.
AB  - Fluorescent tracers for glucose-uptake monitoring could be used as chemical tools
      for diagnosis and for discovery of novel therapeutic agents via the development
      of phenotypic screening systems. Here we present a new near-infrared fluorescent
      glucose tracer, Glc-SiR-CO2H, for monitoring the cellular glucose uptake. By
      conjugating glucosamine with two different silicon rhodamine fluorochromes, we
      found that the net charge of fluorochromes has considerable effects on cellular
      uptake of the probe. Competition assay with d/l-glucose as well as Western blot
      analysis implied GLUT-dependent uptake mechanism of this probe. Finally, Glc-SiR
      CO2H not only differentiates cancer cells from normal cells, but also allows
      monitoring anticancer effects in live cells.

PMID- 30183257
TI  - Bfd, a New Class of [2Fe-2S] Protein That Functions in Bacterial Iron
      Homeostasis, Requires a Structural Anion Binding Site.
AB  - Mobilization of iron from bacterioferritin (BfrB) requires specific interactions
      with a [2Fe-2S] ferredoxin (Bfd). Blocking the BfrB:Bfd interaction results in
      irreversible iron accumulation in BfrB and iron deficiency in the cytosol
      [Eshelman, K., et al. (2017) Metallomics 9, 646-659]. The only known Bfd
      structure, which was obtained in complex with BfrB (Protein Data Bank entry 4E6K
      ), indicated a new fold and suggested that the stability of Bfd is aided by an
      anion binding site consisting of R26, R29, and K46. We investigated the Bfd fold
      using site-directed mutagenesis, X-ray crystallography, and biochemistry in
      solution. The X-ray structure, which is nearly identical to that of Bfd in the
      BfrB:Bfd complex, shows that the [2Fe-2S] cluster preorganizes residues at the
      BfrB:Bfd interface into a structure complementary to the Bfd binding site on
      BfrB. Studies in solution showed rapid loss of the [2Fe-2S] cluster at a low
      ionic strength but higher stability with an increasing ionic strength, thus
      supporting a structural anion binding site. Structures of the R26E and R26E/K46Y
      mutants are nearly identical to that of Bfd, except for a new network of hydrogen
      bonds stabilizing the region encompassing the former anion binding site. The
      stability of the R26E and R26E/K46Y mutants, which is weakly and completely
      independent of solution ionic strength, respectively, corroborates that Bfd
      requires an anion binding site. The mutations, which caused only small changes to
      the strength of the BfrB:Bfd interaction and mobilization of iron from BfrB,
      indicate that the anion binding site in Bfd serves primarily a structural role.

PMID- 30183258
TI  - High-Density Ultra-small Clusters and Single-Atom Fe Sites Embedded in Graphitic
      Carbon Nitride (g-C3N4) for Highly Efficient Catalytic Advanced Oxidation
      Processes.
AB  - Ultra-small metal clusters have attracted great attention owing to their superior
      catalytic performance and extensive application in heterogeneous catalysis.
      However, the synthesis of high-density metal clusters is very challenging due to
      their facile aggregation. Herein, one-step pyrolysis was used to synthesize ultra
      small clusters and single-atom Fe sites embedded in graphitic carbon nitride with
      high density (iron loading up to 18.2 wt %), evidenced by high-angle annular dark
      field-scanning transmission electron microscopy, X-ray absorption spectroscopy, X
      ray photoelectron spectroscopy, and 57Fe Mossbauer spectroscopy. The catalysts
      exhibit enhanced activity and stability in degrading various organic samples in
      advanced oxidation processes. The drastically increased metal site density and
      stability provide useful insights into the design and synthesis of cluster
      catalysts for practical application in catalytic oxidation reactions.

PMID- 30183259
TI  - Rapid Discovery of Glycocins through Pathway Refactoring in Escherichia coli.
AB  - Glycocins (glycosylated bacteriocins) are a family of ribosomally synthesized and
      post-translationally modified peptides with antimicrobial activities against
      pathogens of interest, including methicillin-resistant Staphylococcus aureus,
      representing a promising source of new antibiotics. Glycocins are still largely
      underexplored, and thus far, only six glycocins are known. Here, we used genome
      mining to identify 50 putative glycocin biosynthetic gene clusters and then chose
      six of them with distinct features for further investigation. Through two rounds
      of plug-and-play pathway refactoring and expression in Escherichia coli
      BL21(DE3), four systems produced novel glycocins. Further structural
      characterization revealed that one of them, which belongs to the enterocin 96
      type glycocins, was diglucosylated on a single serine. The other three compounds
      belong to the SunA/ThuA-type glycocins and exhibit a antimicrobial spectrum
      narrower than that of sublancin, the best characterized member in this group,
      even though they share a similar disulfide topology and glycosylation. Further
      evaluation of their bioactivities with free glucose at high concentrations
      suggested that their antimicrobial mechanisms might be both glycocin- and species
      specific. These glycocins with distinct features significantly broaden our
      knowledge and may lead to the discovery of new classes of antibiotics.

PMID- 30183260
TI  - Vaginal Product Formulation Alters the Innate Antiviral Activity and Glycome of
      Cervicovaginal Fluids with Implications for Viral Susceptibility.
AB  - Glycosylated proteins (i.e., mucins, IgG) are important mediators of innate
      antiviral immunity in the vagina; however, our current knowledge of the role that
      glycan themselves play in genital immunity is relatively low. Herein, we evaluate
      the relationship between innate antiviral immunity and glycomic composition in
      cervicovaginal lavage fluid (CVL) collected as part of a Phase I clinical trial
      testing the impact of two distinct formulations of the antiretroviral drug
      dapivirine. Using lectin microarray technology, we discovered that formulation
      (hydrogel- versus film-based delivery) impacted the CVL glycome, with hydrogel
      formulations inducing more changes, including a loss of high-mannose. The loss of
      this epitope correlated to a loss of anti-HIV-1 activity. Glycoproteomic
      identification of high-mannose proteins revealed a cohort of antiproteases shown
      to be important in HIV-1 resistance, whose expression covaried with the high
      mannose signature. Our data strongly suggests high-mannose as a marker for
      secreted proteins mediating innate antiviral immunity in vaginal fluids and that
      drug formulation may impact this activity as reflected in the glycome.

PMID- 30183261
TI  - Overcoming Site Heterogeneity In Search of Metal Nanocatalysts.
AB  - Site heterogeneity of metal nanocatalysts poses grand challenges for catalyst
      design from first principles. To accelerate catalyst discovery, it is of pivotal
      importance to develop an approach that efficiently maps catalytic activity of
      nanoparticles onto geometry-based descriptors while considering the geometric
      strain and metal ligand of an active site. We demonstrate that there exist linear
      correlations between orbitalwise coordination numbers CNalpha and free formation
      energies of oxygen species (e.g., *OH and *OOH) at Pt sites. Kinetic analysis
      along with herein developed structure-activity relationships accurately predicts
      the activity trend of pure Pt nanoparticles (~1-7 nm) toward oxygen reduction.
      Application of the approach to a search of Pt nanoalloys leads to several Pt
      monolayer core-shell nanostructures with enhanced oxygen reduction activity and
      reduced cost. The approach presented here facilitates a transition from
      traditional single-crystal models to nanoparticles in theory-guided catalyst
      discovery.

PMID- 30183262
TI  - Copper-Catalyzed Radical Relay for Asymmetric Radical Transformations.
AB  - The direct transformation of C-H bonds into diverse functional groups represents
      one of the most atom- and step-economical strategies for organic synthesis and
      has received substantial attention over the last few decades. Despite recent
      advances, asymmetric C-H bond functionalizations are less developed, especially
      asymmetric oxidations of sp3 C-H bonds. Inspired by enzyme (e.g., P450)
      catalysis, chemists have made great efforts to develop non-enzymatic systems for
      enantioselective oxidations of sp3 C-H bonds. However, the involvement of highly
      reactive radical intermediates makes enantioselective transformations extremely
      challenging. In this Account, we present our recent studies on the
      enantioselective induction of prochiral benzylic radicals using a chiral
      bisoxazoline (Box)/Cu catalytic system. This reaction system was developed on the
      basis of our extensive studies of copper-catalyzed intermolecular alkene
      difunctionalizations, such as azidotrifluoromethylations,
      trifluoromethylcyanations, and trifluoromethylarylations. In these reactions, the
      proposed catalytic cycle starts from the oxidation of the Cu(I) species by the
      activated Togni-I reagent (via a Lewis acid/base interaction with a silyl reagent
      or arylboronic acid) through a single electron transfer process. The generated
      CF3 radical can efficiently add to the alkene, and the resultant carbon-centered
      radical is subsequently trapped by an active Cu(II) species bearing a nucleophile
      (e.g., an N3, CN, or Ar moiety) to form a new C-heteroatom or C-C bond and
      regenerate the Cu(I) catalyst. Kinetic studies of the trifluoromethylarylation of
      alkenes support a Cu(I/II/III) catalytic cycle in which the carbon radical reacts
      with the Cu(II) species to form a highly reactive Cu(III) intermediate and its
      reductive elimination contributes to the final bond formation. This assumption
      inspired us to explore asymmetric radical transformations by introducing chiral
      ligands. Enantioselective cyanations and arylations of benzylic radicals have
      been demonstrated in the presence of chiral Box/Cu(I) catalysts, and a series of
      asymmetric difunctionalizations of styrenes have been successfully achieved. In
      addition, by means of the same benzylic radical trapping process,
      enantioselective decarboxylative cyanations have been demonstrated using a
      cooperative photocatalysis and copper catalysis system. Compared with radical
      addition and decarboxylative processes, hydrogen atom abstraction (HAA) provides
      direct and facile access to benzylic radicals. By using bisbenzenesulfonimidyl
      radical for HAA, our group has developed an enantioselective cyanation of
      benzylic C-H bonds via a copper-catalyzed radical relay, and excellent reactivity
      and enantioselectivity were achieved in the presence of chiral Box/Cu(I)
      catalysts. In addition, a regioselective benzylic C-H bond arylation proceeding
      through a similar process was also developed, providing simple access to 1,1
      diarylalkanes. Notably, alkyl arenes were used as the limiting reagent in these
      reactions, which allowed the late-stage functionalization of sp3 C-H bonds in
      complex molecules, including natural products, pharmaceuticals, and
      agrochemicals.

PMID- 30183263
TI  - Directed Self-Assembly of C4-Symmetric, Oxidovanadate-Centered, Vanadyl(V)
      Quadruplexes for Ba2+- and Hg2+-Specific Recognition, Transport, and Recovery.
AB  - Directed assembly of loosely, Na+-bound, oxidovanadate-centered quartets of C4
      symmetry from tailor-made chiral N-salicylidene-vanadyl(V) complexes, for the
      first time, allows for highly efficient Ba2+- or Hg2+-specific detection (by 51V
      NMR and VCD), transport (forming a unique helical capsule or a capped square
      planar complex, respectively), and green recovery from an aqueous phase
      containing 4 different alkaline earth ions or from at least 10 different metal
      ions of similar size and charge capacity into the CHCl3 layer without
      interference from oxa- or oxophilic ions like Mg2+, Ca2+, Cu2+, Cd2+, and Pb2+.

PMID- 30183264
TI  - Nucleopore-Inspired Polymer Hydrogels for Selective Biomolecular Transport.
AB  - Biological systems routinely regulate biomolecular transport with remarkable
      specificity, low energy input, and simple mechanisms. Here, the biophysical
      mechanisms of nuclear transport inspire the development of gels for recognition
      and selective permeation (GRASP). GRASP presents a new paradigm for specific
      transport and selective permeability, in which binding interactions between a
      biomolecule and a hydrogel lead to faster penetration of the gel. A molecular
      transport theory identifies key principles for selective transport: entropic
      repulsion of noninteracting molecules and affinity-mediated diffusion of
      multireceptor biomolecules through a walking mechanism. The ability of
      interacting molecules to walk through hydrogels enables enhanced permeability in
      polymer networks. To realize this theoretical prediction in a novel material,
      GRASP is engineered from a poly(ethylene glycol) network (entropic barrier)
      containing antibody-binding oligopeptides (affinity domains). GRASP is
      synthesized using simultaneous bioconjugation and polycondensation reactions. The
      elastic modulus, characteristic pore size, biomolecular diffusivity, and
      selective permeability are measured in the resulting materials, which are applied
      to regulate the transport of equally sized molecules by preferentially
      transporting a monoclonal antibody from a polyclonal mixture. Overall, this work
      presents rationally designed, nucleopore-inspired hydrogels that are capable of
      controlling biomolecular transport.

PMID- 30183265
TI  - Thermodynamics of Iron(II) and Substrate Binding to the Ethylene-Forming Enzyme.
AB  - The ethylene-forming enzyme (EFE), like many other 2-oxoglutarate (2OG)-dependent
      nonheme iron(II) oxygenases, catalyzes the oxidative decarboxylation of 2OG to
      succinate and CO2 to generate a highly reactive iron species that hydroxylates a
      specific alkane C-H bond, in this case targeting l-arginine (Arg) for
      hydroxylation. However, the prominently observed reactivity of EFE is the
      transformation of 2OG into ethylene and three molecules of CO2. Crystallographic
      and biochemical studies have led to several proposed mechanisms for this 2-fold
      reactivity, but the detailed reaction steps are still obscure. Here, the
      thermodynamics associated with iron(II), 2OG, and Arg binding to EFE are studied
      using calorimetry (isothermal titration calorimetry and differential scanning
      calorimetry) to gain insight into how these binding equilibria organize the
      active site of EFE, which may have an impact on the O2 activation pathways
      observed in this system. Calorimetric data show that the addition of iron(II),
      Arg, and 2OG increases the stability over that of the apoenzyme, and there is
      distinctive cooperativity between substrate and cofactor binding. The energetics
      of binding of 2OG to Fe.EFE are consistent with a unique monodentate binding
      mode, which is different than the prototypical 2OG coordination mode in other 2OG
      dependent oxygenases. This difference in the pre-O2 activation equilibria may be
      important for supporting the alternative ethylene-forming chemistry of EFE.

PMID- 30183266
TI  - Secondary Photocrosslinking of Click Hydrogels To Probe Myoblast
      Mechanotransduction in Three Dimensions.
AB  - Muscle cells sense the mechanical properties of their microenvironment, and these
      properties can change in response to injury or disease. Hydrogels with dynamic
      material properties can be used to study the effect of such varying mechanical
      signals. Here, we report the ability of azadibenzocyclooctyne to undergo a
      cytocompatible, photoinitiated crosslinking reaction. This reaction is exploited
      as a strategy for on-demand stiffening of three-dimensional cell scaffolds formed
      through an initial strain-promoted azide-alkyne cycloaddition. Myoblasts
      encapsulated in these networks respond to increased matrix stiffness through
      decreased cell spreading and nuclear localization of Yes-associated protein 1
      (YAP). However, when the photocrosslinking reaction is delayed to allow cell
      spreading, elongated myoblasts display increased YAP nuclear localization.

PMID- 30183268
TI  - Layer-by-Layer Manipulation of Heterogeneous Rectangular Nanoblocks: Brick Work
      for Multilayered Structures with Specific Heterojunction.
AB  - The combination of heterogeneous inorganic nanocrystals provides novel nanometer
      scale architectures for exploration of novel functions. In the present study,
      heterogeneous bilayers, such as BaTiO3-Fe3O4 and Mn3O4-CeO2, are fabricated via
      layer-by-layer stacking of several rectangular nanoblocks 5-23 nm in size by
      evaporation-driven self-assembly. Specific heterojunctions between inorganic
      crystals are constructed by nanoscale simple brick work through spontaneous
      adjustment of the crystallographic orientations of the nanoblocks in the lower
      and upper layers.

PMID- 30183267
TI  - Versatile Uranyl Germanate Framework Hosting 12 Different Alkali Halide 1D Salt
      Inclusions.
AB  - Single crystals of 13 new uranyl germanate salt-inclusion materials were grown
      from alkali halide fluxes: [Cs2Cs5F][(UO2)3(Ge2O7)2] (1),
      [Cs6Ag2Cl2][(UO2)3(Ge2O7)2] (2), [Cs6Ag0.3Na1.7Cl2][(UO2)3(Ge2O7)2] (3),
      [Cs6Ag0.4Na1.6Cl2][(UO2)3(Ge2O7)2] (4), [Cs6K2Cl2][(UO2)3(Ge2O7)2] (5),
      [Cs6K1.9Ag0.1Cl2][(UO2)3(Ge2O7)2] (6), [KK6Cl][(UO2)3(Ge2O7)2] (7),
      [KK6Br0.6F0.4][(UO2)3(Ge2O7)2] (8), [Na0.9Rb6.1F][(UO2)3(Ge2O7)2] (9),
      [K0.6Na0.4K5CsCl0.5F0.5][(UO2)3(Ge2O7)2] (10),
      [K0.8Na0.2K4.8Cs1.2Cl0.5F0.5][(UO2)3(Ge2O7)2] (11), [KK1.8Cs4.2F][(UO2)3(Ge2O7)2]
      (12), and [Cs6Cs0.71Cl0.71][(UO2)3O3(Ge2O7)] (13). Structures 1-12 contain the
      same [(UO2)3(Ge2O7)2]6- framework whose pores are filled with varied salt species
      selected by the choice of the specific alkali halide flux used for crystal
      growth. The size and identity of the salt species also influence whether the
      [(UO2)3(Ge2O7)2]6- framework adopts a monoclinic or orthorhombic symmetry. The
      13th composition, [Cs6Cs0.71Cl0.71][(UO2)3O3(Ge2O7)] (13), crystallizes in a new
      structure type in the hexagonal crystal system and contains large channels.
      Optical characterization was performed on [Cs6K1.9Ag0.1Cl2][(UO2)3(Ge2O7)2] (6)
      and [KK1.8Cs4.2F][(UO2)3(Ge2O7)2] (12), and both exhibit UV-vis absorption and
      luminescence typical of the uranyl group. The fluorine-containing composition
      luminesces 10 times as intensely as does the chlorine-containing composition.

PMID- 30183269
TI  - Mycofactocin Biosynthesis Proceeds through 3-Amino-5-[( p-hydroxyphenyl)methyl]
      4,4-dimethyl-2-pyrrolidinone (AHDP); Direct Observation of MftE Specificity
      toward MftA.
AB  - The structure of the ribosomally synthesized and post-translationally modified
      peptide product mycofactocin is unknown. Recently, the first step in mycofactocin
      biosynthesis was shown to be catalyzed by MftC in two S-adenosylmethionine
      dependent steps. In the first step, MftC catalyzes the oxidative decarboxylation
      of the MftA peptide to produce the styrene-containing intermediate MftA**,
      followed by a subsequent C-C bond formation to yield the lactam-containing MftA*.
      Here, we demonstrate the subsequent biosynthetic step catalyzed by MftE is
      specific for MftA*. The hydrolysis of MftA* leads to the formation of MftA(1-28)
      and 3-amino-5-[( p-hydroxyphenyl)methyl]-4,4-dimethyl-2-pyrrolidinone (AHDP). The
      hydrolysis reaction is Fe2+-dependent, and addition of the metal to the reaction
      mixture leads to a kobs of ~0.2 min-1. Lastly, we validate the structure of AHDP
      by 1H, 13C, and COSY nuclear magnetic resonance techniques as well as mass
      spectrometry.

PMID- 30183270
TI  - Chlorophyll-Carotenoid Excitation Energy Transfer in High-Light-Exposed Thylakoid
      Membranes Investigated by Snapshot Transient Absorption Spectroscopy.
AB  - Nonphotochemical quenching (NPQ) provides an essential photoprotection in plants,
      assuring safe dissipation of excess energy as heat under high light. Although
      excitation energy transfer (EET) between chlorophyll (Chl) and carotenoid (Car)
      molecules plays an important role in NPQ, detailed information on the EET
      quenching mechanism under in vivo conditions, including the triggering mechanism
      and activation dynamics, is very limited. Here, we observed EET between the Chl Q
      y state and the Car S1 state in high-light-exposed spinach thylakoid membranes.
      The kinetic and spectral analyses using transient absorption (TA) spectroscopy
      revealed that the Car S1 excited state absorption (ESA) signal after Chl
      excitation has a maximum absorption peak around 540 nm and a lifetime of ~8 ps.
      Snapshot TA spectroscopy at multiple time delays allowed us to track the Car S1
      ESA signal as the thylakoid membranes were exposed to various light conditions.
      The obtained snapshots indicate that maximum Car S1 ESA signal quickly rose and
      slightly dropped during the initial high-light exposure (<3 min) and then
      gradually increased with a time constant of ~5 min after prolonged light
      exposure. This suggests the involvement of both rapidly activated and slowly
      activated mechanisms for EET quenching. 1,4-Dithiothreitol (DTT) and 3,3'
      dithiobis(sulfosuccinimidyl propionate) (DTSSP) chemical treatments further
      support that the Car S1 ESA signal (or the EET quenching mechanism) is primarily
      dependent on the accumulation of zeaxanthin and partially dependent on the
      reorganization of membrane proteins, perhaps due to the pH-sensing protein
      photosystem II subunit S.

PMID- 30183271
TI  - Correction to Photocontrolled Fluorescence "Double-Check" Bioimaging Enabled by a
      Glycoprobe-Protein Hybrid.

PMID- 30183272
TI  - Synergistic Boron Doping of Semiconductor and Dielectric Layers for High
      Performance Metal Oxide Transistors: Interplay of Experiment and Theory.
AB  - We report the results of a study to enhance metal oxide (MO) thin-film transistor
      (TFT) performance by doping both the semiconductor (In2O3) and gate dielectric
      (Al2O3) layers with boron (yielding IBO and ABO, respectively) and provide the
      first quantitative analysis of how B doping affects charge transport in these MO
      dielectric and semiconducting matrices. The impact of 1-9 atom % B doping on MO
      microstructure, morphology, oxygen defects, charge transport, and dielectric
      properties is analyzed together, in detail, by complementary experimental
      (microstructural, electrical) and theoretical (ab initio MD, DFT) methods. The
      results indicate that B doping frustrates In2O3 crystallization while suppressing
      defects responsible for electron trapping and carrier generation. In the adjacent
      Al2O3 dielectric, B doping increases the dielectric constant and refractive index
      while reducing leakage currents. Furthermore, optimized solution-processed TFTs
      combining IBO channels with 6 atom % B and ABO dielectrics with 10 atom % B
      exhibit field effect mobilities as high as 11 cm2 V-1 s-1, current on/off ratios
      >105, threshold voltages = 0.6 V, and superior bias stress durability.

PMID- 30183273
TI  - Modular Pincer-type Pyridylidene Amide Ruthenium(II) Complexes for Efficient
      Transfer Hydrogenation Catalysis.
AB  - A set of bench-stable ruthenium complexes with new N,N,N-tridentate coordinating
      pincer-type pyridyl-bis(pyridylideneamide) ligands was synthesized in excellent
      yields, with the pyridylidene amide in meta or in para position ( m-PYA and p
      PYA, respectively). While complex [Ru( p-PYA)(MeCN)3]2+ is catalytically silent
      in transfer hydrogenation, its meta isomer [Ru( m-PYA)(MeCN)3]2+ shows
      considerable activity with turnover frequencies at 50% conversion TOF50 = 100 h
      1. Spectroscopic, electrochemical, and crystallographic analyses suggest
      considerably stronger donor properties of the zwitterionic m-PYA ligand compared
      to the partially pi-acidic p-PYA analogue, imparted by valence isomerization.
      Further catalyst optimization was achieved by exchanging the ancillary MeCN
      ligands with imines (4-picoline), amines (ethylenediamine), and phosphines (PPh3,
      dppm, dppe). The most active catalyst was comprised of the m-PYA pincer ligand
      and PPh3, complex [Ru( m-PYA)(PPh3)(MeCN)2]2+, which reached a TOF50 of 430 h-1
      under aerobic conditions and up to 4000 h-1 in the absence of oxygen. The
      presence of oxygen reversibly deactivates the catalytically active species, which
      compromises activity, but not longevity of the catalyst. Ligand exchange kinetic
      studies by NMR spectroscopy indicate that the strong trans effect of the
      phosphine is critical for high catalyst activity. Diaryl, aryl-alkyl, and dialkyl
      ketones were hydrogenated with high conversion, and alpha,beta-unsaturated
      ketones produced selectively the saturated ketone as the only product due to
      exclusive C?C bond hydrogenation, a distinctly different selectivity from most
      other transfer hydrogenation catalysts.

PMID- 30183274
TI  - Mechanistic Studies of the Protonation-Deprotonation Reactions for Type 1 and
      Type 2 Isopentenyl Diphosphate:Dimethylallyl Diphosphate Isomerase.
AB  - Type 1 and type 2 isopentenyl diphosphate:dimethylallyl diphosphate isomerase
      (IDI-1 and IDI-2) catalyze the interconversion of isopentenyl diphosphate (IPP)
      and dimethylallyl diphosphate (DMAPP), the fundamental building blocks for
      biosynthesis of isoprenoid compounds. Previous studies indicate that both
      isoforms of IDI catalyze isomerization by a protonation-deprotonation mechanism.
      IDI-1 and IDI-2 are "sluggish" enzymes with turnover times of ~10 s-1 and ~1 s-1,
      respectively. We measured incorporation of deuterium into IPP and DMAPP in D2O
      buffer for IDI-1 and IDI-2 under conditions where newly synthesized DMAPP is
      immediately and irreversibly removed by coupling its release to condensation with
      l-tryptophan catalyzed by dimethylallyltrytophan synthase. During the course of
      the reactions, we detected formation of d1, d2, and d3 isotopologues of IPP and
      DMAPP, which were formed during up to five isomerizations between IPP and DMAPP
      during each turnover. The patterns for deuterium incorporation into IPP show that
      d2-IPP is formed in preference to d1-IPP for both enzymes. Analysis of the
      patterns of deuterium incorporation are consistent with a mechanism involving
      addition and removal of protons by a concerted asynchronous process, where
      addition substantially precedes removal, or a stepwise process through a short
      lived (<3 ps) tertiary carbocationic intermediate. Previous work with mechanism
      based inhibitors and related model studies supports a concerted asynchronous
      mechanism for the enzyme-catalyzed isomerizations.

PMID- 30183275
TI  - Thermal Denaturation of DNA G-Quadruplexes and Their Complexes with Ligands:
      Thermodynamic Analysis of the Multiple States Revealed by Mass Spectrometry.
AB  - Designing ligands targeting G-quadruplex nucleic acid structures and affecting
      cellular processes is complicated because there are multiple target sequences and
      some are polymorphic. Further, structure alone does not reveal the driving forces
      for ligand binding. To know why a ligand binds, the thermodynamics of binding
      must be characterized. Electrospray mass spectrometry enables one to detect and
      quantify each specific stoichiometry (number of strands, cations, and ligands)
      and thus to simultaneously determine the equilibrium constants for each complex.
      Using a temperature-controlled nanoelectrospray source, we determined the
      temperature dependence of the equilibrium constants, and thus the enthalpic and
      entropic contributions to the formation of each stoichiometry. Enthalpy drives
      the formation of each quartet-K+-quartet unit, whereas entropy drives the
      formation of quartet-K+-triplet units. Consequently, slip-stranded structures can
      become more abundant as the temperature increases. In the presence of ligands
      (Phen-DC3, TrisQ, TMPyP4, Cu-ttpy), we observed that, even when only a 1:1
      (ligand/quadruplex) complex is observed at room temperature, new states are
      populated at intermediate temperatures, including 2:1 complexes. In most cases,
      ligand-G4-quadruplex binding is entropically driven, and we discuss that this may
      have resulted from biases when ranking ligand potency using melting experiments.
      Other thermodynamic profiles could be linked to topology changes in terms of
      number of G-quartets (reflected in the number of specific K+ ions in the
      complex). The thermodynamics of ligand binding to each form, one ligand at a
      time, provides unprecedented detail on the interplay between ligand binding and
      topology changes in terms of number of G-quartets.

PMID- 30183276
TI  - Fluorine as a Traceless Directing Group for the Regiodivergent Synthesis of
      Indoles and Tryptophans.
AB  - Despite ample evidence for the unique reactivity offered by hypervalent F
      iodanes, mechanistic investigations fall far behind. In order to shed light on
      the unusual behavior of such F-reagents, we conducted computational and
      experimental studies on the chemodivergent transformation of styrenes. We
      identified the spirocyclic F-cyclopropane as the common intermediate for both the
      C, H-fluorination and C, H-amination pathways. The fate of this key compound is
      determined by the extent of cationic charge delocalization controlled by the N
      substituents. Exploiting this phenomenon, a multitude of different
      transformations have become available, leading, i.e., to the regiodivergent
      synthesis of indoles and tryptophans.

PMID- 30183277
TI  - Elucidating the Role of Molecule-Electrode Interfacial Defects in Charge
      Tunneling Characteristics of Large-Area Junctions.
AB  - Interfacial chemistry at organic-inorganic contact critically determines the
      function of a wide range of molecular and organic electronic devices and other
      systems. The chemistry is, however, difficult to understand due to the lack of
      easily accessible in-operando spectroscopic techniques that permit access to
      interfacial structure on a molecular scale. Herein, we compare two analogous
      junctions formed with identical organic thin film and different liquid top
      contacts (water droplet vs eutectic gallium indium alloy) and elucidate the
      puzzling interfacial characteristics. Specifically, we fine-tune the surface
      topography of the organic surface using mixed self-assembled monolayers (SAMs):
      single component SAM composed of rectifier (2,2'-bipyridyl-terminated n
      undecanethiolate; denoted as SC11BIPY) is systematically diluted with
      nonrectifying n-alkanethiolates of different lengths (denoted as SC n where n =
      8, 10, 12, 14, 16, 18). Characterization of the resulting mixed SAMs in
      wettability and tunneling currents with the two separate liquid top-contacts
      allows us to investigate the role of phase segregation and gauche defect in the
      SAM//liquid interfaces. The results reported here show the difference in length
      between SC11BIPY and SC n is translated into nanoscopic pits and gauche-conformer
      defects on the surface, and the difference in contact force-hydrostatic vs user
      pressures-and hence conformity of contact account for the difference in
      wettability and rectification behaviors. Our work provides an insight into the
      role of molecule-electrode interfacial defects in performance of molecular-scale
      electronic devices.

PMID- 30183278
TI  - Kinetic Understanding of N2 Reduction versus H2 Evolution at the E4(4H) Janus
      State in the Three Nitrogenases.
AB  - The enzyme nitrogenase catalyzes the reduction of N2 to ammonia but also that of
      protons to H2. These reactions compete at the mechanistically central 'Janus'
      intermediate, denoted E4(4H), which has accumulated 4e-/4H+ as two bridging Fe-H
      Fe hydrides on the active-site cofactor. This state can lose e-/H+ by hydride
      protonolysis (HP) or become activated by reductive elimination ( re) of the two
      hydrides and bind N2 with H2 loss, yielding an E4(2N2H) state that goes on to
      generate two NH3 molecules. Thus, E4(4H) represents the key branch point for
      these competing reactions. Here, we present a steady-state kinetic analysis that
      precisely describes this competition. The analysis demonstrates that steady
      state, high-electron flux turnover overwhelmingly populates the E4 states at the
      expense of less reduced states, quenching HP at those states. The ratio of rate
      constants for E4(4H) hydride protonolysis ( kHP) versus reductive elimination (
      kre) provides a sensitive measure of competition between these two processes and
      thus is a central parameter of nitrogenase catalysis. Analysis of measurements
      with the three nitrogenase variants (Mo-nitrogenase, V-nitrogenase, and Fe
      nitrogenase) reveals that at a fixed N2 pressure their tendency to productively
      react with N2 to produce two NH3 molecules and an accompanying H2, rather than
      diverting electrons to the side reaction, HP production of H2, decreases with
      their ratio of rate constants, k re/ kHP: Mo-nitrogenase, 5.1 atm-1; V
      nitrogenase, 2 atm-1; and Fe-nitrogenase, 0.77 atm-1 (namely, in a 1:0.39:0.15
      ratio). Moreover, the lower catalytic effectiveness of the alternative
      nitrogenases, with more H2 production side reaction, is not caused by a higher
      kHP but by a significantly lower k re.

PMID- 30183279
TI  - Rapid Screening of Lanthipeptide Analogs via In-Colony Removal of Leader Peptides
      in Escherichia coli.
AB  - Most native producers of ribosomally synthesized and post-translationally
      modified peptides (RiPPs) utilize N-terminal leader peptides to avoid potential
      cytotoxicity of mature products to the hosts. Unfortunately, the native machinery
      of leader peptide removal is often difficult to reconstitute in heterologous
      hosts. Here we devised a general method to produce bioactive lanthipeptides, a
      major class of RiPP molecules, in Escherichia coli colonies using synthetic
      biology principles, where leader peptide removal is programmed temporally by
      protease compartmentalization and inducible cell autolysis. We demonstrated the
      method for producing two lantibiotics, haloduracin and lacticin 481, and
      performed analog screening for haloduracin. This method enables facile, high
      throughput discovery, characterization, and engineering of RiPPs.

PMID- 30183280
TI  - Targeted m6A Reader Proteins To Study Epitranscriptomic Regulation of Single
      RNAs.
AB  - Post-transcriptional gene expression regulation of RNA has emerged as a key
      factor that controls mammalian protein production. RNA trafficking, translation
      efficiency, and stability are all controlled at the transcript level. For
      example, in addition to the commonly known processing steps of capping, splicing,
      and polyadenylation, RNA can be chemically modified. In eukaryotes, N6
      methyladenosine (m6A) is the most prevalent mRNA modification. While the writers,
      erasers, and readers for m6A are rapidly being uncovered and studied at the whole
      cell level, their competitive interplay to regulate methylated RNA transcripts
      has yet to be elucidated. To address this limitation, we report the development
      of programmable dPspCas13b-m6A reader proteins to investigate the regulatory
      effects of specific readers on single transcripts in live cells. We fused the two
      most well-characterized m6A reader proteins, YTHDF1 and YTHDF2, to a
      catalytically inactive PspCas13b protein, which can target the reader to a
      specific RNA of interest using guide RNA (gRNA) complementarity. We then
      demonstrate that the fused reader proteins each retain their reported functional
      role on a reporter construct: YTHDF2 induces degradation and YTHDF1 enhances
      translation. Finally, we show that the system can target endogenous mRNA
      transcripts within cells, using YTHDF2 as an exemplar, where we found tethering
      with YTHDF2 leads to decay of the target transcript. The development of dCas13b
      based tools to study the regulation of endogenous RNAs will dramatically enhance
      our understanding of how RNA regulation occurs at the single RNA level.
      Additionally, our new tools, which permit transcript-specific mediated decay or
      enhanced protein production, will find utility in synthetic biology applications
      aimed at controlling genetic information flow at the RNA level.

PMID- 30183281
TI  - Chromophore-Protein Interplay during the Phytochrome Photocycle Revealed by Step
      Scan FTIR Spectroscopy.
AB  - Phytochrome proteins regulate many photoresponses of plants and microorganisms.
      Light absorption causes isomerization of the biliverdin chromophore, which
      triggers a series of structural changes to activate the signaling domains of the
      protein. However, the structural changes are elusive, and therefore the molecular
      mechanism of signal transduction remains poorly understood. Here, we apply two
      color step-scan infrared spectroscopy to the bacteriophytochrome from Deinococcus
      radiodurans. We show by recordings in H2O and D2O that the hydrogen bonds to the
      biliverdin D-ring carbonyl become disordered in the first intermediate (Lumi-R)
      forming a dynamic microenvironment, then completely detach in the second
      intermediate (Meta-R), and finally reform in the signaling state (Pfr). The
      spectra reveal via isotope labeling that the refolding of the conserved "PHY
      tongue" region occurs with the last transition between Meta-R and Pfr. Additional
      changes in the protein backbone are detected already within microseconds in Lumi
      R. Aided by molecular dynamics simulations, we find that a strictly conserved
      salt bridge between an arginine of the PHY tongue and an aspartate of the
      chromophore binding domains is broken in Lumi-R and the arginine is recruited to
      the D-ring C?O. This rationalizes how isomerization of the chromophore is linked
      to the global structural rearrangement in the sensory receptor. Our findings
      advance the structural understanding of phytochrome photoactivation.

PMID- 30183282
TI  - Discovery of New Allosteric Modulators of the Urotensinergic System through
      Substitution of the Urotensin II-Related Peptide (URP) Phenylalanine Residue.
AB  - Urotensin II (UII) and urotensin II-related peptide (URP) are functionally
      selective, suggesting that these two hormones might play distinct physiological
      role through different interactions with their cognate receptor UT. Hypothesizing
      that the Phe3 residue of URP, which is also present in UII, is a key-element of
      its specific UT activation, we evaluated the impact of its replacement by non
      natural amino acids in URP. Each compound was evaluated for its ability to bind
      UT, induce rat aortic ring contraction, and activate Gq, G12, and beta-arrestin 1
      signaling pathways. Such modifications impaired contractile efficacy, reflected
      by a reduced aptitude to activate G12 in URP but not in the truncated but
      equipotent UII4-11. Moreover, we have identified two structurally different UT
      modulators: [d-Phe(pI)3]URP and [Bip3]URP, which exert a probe-dependent action
      against UII and URP. These compounds should help us understand the specific roles
      of these hormones as well as guide further therapeutic development.

PMID- 30183283
TI  - Nickel(0)-Catalyzed Hydroalkylation of 1,3-Dienes with Simple Ketones.
AB  - We developed a highly regioselective addition of 1,3-dienes with simple ketones
      by nickel-hydride catalyst bearing DTBM-SegPhos ligand. A wide range of aromatic
      and aliphatic ketones directly coupled with 1,3-dienes, providing synthetically
      useful gamma,delta-unsaturated ketones in high yield and regioselectivity. The
      asymmetric version of the reaction was also realized in high enantioselectivity
      by using novel chiral ligand DTBM-HO-BIPHEP. The utility of this hydroalkylation
      was demonstrated by facile product modification and enantioselective synthesis of
      ( R)-flobufen.

PMID- 30183284
TI  - Structural Dynamics of Lateral and Diagonal Loops of Human Telomeric G
      Quadruplexes in Extended MD Simulations.
AB  - The NMR solution structures of human telomeric (Htel) G-quadruplexes (GQs) are
      characterized by the presence of two lateral loops complemented by either
      diagonal or propeller loops. Bases of a given loop can establish interactions
      within the loop as well as with other loops and the flanking bases. This can lead
      to a formation of base alignments above and below the GQ stems. These base
      alignments are known to affect the loop structures and relative stabilities of
      different Htel GQ folds. We have carried out a total of 217 MUs of classical
      (unbiased) molecular dynamics (MD) simulations starting from the available
      solution structures of Htel GQs to characterize structural dynamics of the
      lateral and diagonal loops, using several recent AMBER DNA force-field variants.
      As the loops are involved in diverse stacking and H-bonding interactions, their
      dynamics is slow, and extended sampling is required to capture different
      conformations. Nevertheless, although the simulations are far from being
      quantitatively converged, the data suggest that multiple 10 MUs-scale simulations
      can provide a quite good assessment of the loop conformational space as described
      by the force field. The simulations indicate that the lateral loops may sample
      multiple coexisting conformations, which should be considered when comparing
      simulations with the NMR models as the latter include ensemble averaging. The
      adenine-thymine Watson-Crick arrangement was the most stable base pairing in the
      simulations. Adenine-adenine and thymine-thymine base pairs were also sampled but
      were less stable. The data suggest that the description of lateral and diagonal
      GQ loops in contemporary MD simulations is considerably more realistic than the
      description of propeller loops, though definitely not flawless.

PMID- 30183285
TI  - Role of Intramolecular Electron Delocalization in the C-X Bond Strength in CH4-nX
      n ( n = 0-4, X = F, Cl, CN, OCH3).
AB  - Most recently, Wiberg and Rablen examined a few substituted methanes and
      identified the polar effect, which is associated with the atomic charge at the
      central carbon, as a possible factor for bond energy changes while the exact role
      of the hyperconjugation effect is unsettled. In this work, we revisited a series
      of substituted methanes CH4- nX n ( n = 0-4, X= F, Cl, CN, OCH3) by explicitly
      computing the intramolecular electron delocalization energies using the simplest
      variant of ab initio valence bond (VB) theory, namely the block-localized wave
      function (BLW) method. This BLW method is designated to derive electron-localized
      states where intramolecular electron delocalization is "turned off". Computations
      show that the deactivation of the intramolecular electron delocalization in these
      molecules only slightly increases the charge (i.e., reduces the atomic
      population) at the central carbon in all systems. This seems consistent with the
      polar effect therein as proposed by Wiberg and Rablen. But apart from the
      stabilizing polar effect, there should be steric (including both Pauli and
      electrostatic) repulsion among the substituent groups. This is evidenced by the
      stretched C-X bonds in CX4 compared with the same bonds in H3CX (X = Cl, CN) when
      the specific nX' -> sigmaCH/CX* orbital interactions are "turned off", though
      there is indeed notable polar effect in fluoromethanes considering fluorine is
      the most electronegative atom. By focusing on one C-X' bond, we show that its
      involved orbital interactions enhance the bond strength from H3C-F' (by 11.6
      kcal/mol) to F3C-F' (by 18.7 kcal/mol) but weaken from H3C-CN' (by 11.6 kcal/mol)
      to (CN)3C-CN' (by 9.3 kcal/mol).

PMID- 30183286
TI  - Conformational Features of Thioamide-Containing Dipeptoids and Peptoid-Peptide
      Hybrids-Computational and Experimental Approaches.
AB  - The effects of thioamide incorporation into N, N-dimethyl-2-( N
      methylacetamido)acetamide and N-methyl-2-( N-methylacetamido)acetamide as the
      simplest models of a dipeptoid structure and a peptoid-peptide hybrid are
      discussed. The solvent-modulated conformational features of model compounds were
      examined by computations enhanced by natural bond orbital (NBO) analysis and
      experimentally by kinetic and equilibrium measurements using NMR spectroscopy.
      The computations supported by NBO analysis showed that intrinsic stability of the
      predominant trans isomer (alphaD and C7beta forms) of the dipeptoid model results
      from an indirect n -> pi* interaction, occurring between the carbonyl oxygen lone
      pair ( n) and the pi* orbital of the adjacent amide carbonyl through the C-H
      antibond (sigma*). The direct n -> pi* interaction constitutes a negligible
      contribution to trans stabilization. The N-terminal thioxo substitution increases
      this indirect electron delocalization, making the alphaD isomer prevalent. The nX
      -> sigmaN'C-H* interaction is an additional source of stability of the trans
      C7beta form relevant for the underivatized dipeptoid model and its C-terminal
      thioamide counterpart. In the peptoid-peptide hybrid, the trans preference is
      perturbed by subtle differences in the H-bond donor-acceptor abilities between
      the thioxo and oxo groups. The cis isomer becomes more populated with an increase
      in the strength of polarity and the hydrogen bonding acceptor ability of the
      solvent molecules. While thioxo substitution slightly shifts the trans- cis
      equilibrium in polar solvents, it effectively allows for increasing or decreasing
      the barrier to trans- cis rotation with respect to underivatized model compounds
      depending on N- vs C-terminal thioamide backbone substitution.

PMID- 30183287
TI  - Asymmetric Rhodium-Catalyzed Allylic Substitution Reactions: Discovery,
      Development and Applications to Target-Directed Synthesis.
AB  - The transition metal-catalyzed allylic substitution reaction is a particularly
      versatile method for the construction of carbon-carbon and carbon-heteroatom
      bonds. In this regard, the rhodium-catalyzed variant has emerged as a powerful
      method for the regioselective and stereospecific allylic substitution of chiral
      nonracemic secondary and tertiary allylic carbonates with a variety of carbon-
      and heteroatom-based nucleophiles. In addition, recent developments have made the
      analogous enantioselective process possible using prochiral nucleophiles with
      achiral allylic electrophiles, which represents a significant advance in this
      area. In this Perspective, the discovery, development and applications of these
      conceptually orthogonal strategies to target-directed synthesis are discussed,
      with a particular emphasis given to those methods developed in our laboratory.

PMID- 30183288
TI  - Diversity-Oriented Synthesis of Steviol Glycosides.
AB  - With cheap and easily available mixtures of steviol glycosides as starting
      materials, a practical method for steviol acquisition has been developed, on the
      basis of which a facile, diversity-oriented, and economic protocol for the
      synthesis of structurally defined steviol glycosides was established. The novel
      approach is featured by the highly efficient glycosylation of sterically hindered
      and acid-sensitive steviol via orchestrated application of Yu glycosylation,
      Schmidt glycosylation, and PTC glycosylation. Hence, these high-intensity
      sweeteners and potential lead compounds for drug development are now readily
      accessible.

PMID- 30183289
TI  - Colocynthenins A-D, Ring-A seco-Cucurbitane Triterpenoids from the Fruits of
      Citrullus colocynthis.
AB  - Four ring-A seco-cucurbitane triterpenoids, colocynthenins A-D (1-4), together
      with seven known cucurbitane triterpenoids (5-11), were isolated from the fruits
      of Citrullus colocynthis. Their structures and absolute configurations were
      elucidated based on spectroscopic analysis and quantum chemical ECD calculations.
      Compound 1 possesses an unprecedented 2,11-lactone moiety, while compound 2 is
      the first reported cucurbitane triterpenoid with an unusual cyano group.
      Compounds 1 and 3 showed acetylcholinesterase inhibitory activities in a standard
      in vitro assay, with IC50 values of 2.6 and 3.1 MUM, respectively.

PMID- 30183290
TI  - Combination of Capsaicin and Hesperidin Reduces the Effectiveness of Each
      Compound To Decrease the Adipocyte Size and To Induce Browning Features in
      Adipose Tissue of Western Diet Fed Rats.
AB  - We explored the potential of hesperidin and capsaicin, separately and in
      combination, to induce white adipose tissue (WAT) browning and to help body
      weight management in Western diet-fed rats. Adult male Wistar rats were fed for 8
      weeks with Western diet and treated daily with hesperidin (100 mg/kg/day),
      capsaicin (4 mg/kg/day), hesperidin (100 mg/kg/day) + capsaicin (4 mg/kg/day), or
      the vehicle. Hesperidin and capsaicin separately, but not (or to a lesser extent)
      the combination, resulted in a decreased size of adipocytes and induced emergence
      of multilocular brown-like adipocytes positive for UCP1 and CIDEA in
      retroperitoneal WAT. Expression levels of browning markers, such as Prdm16, in
      inguinal WAT also increased with capsaicin treatment compared with the vehicle
      (145% +/- 17% vs 92% +/- 21%, P < 0.05), but no significant effects were found
      with the combination (106% +/- 12%). Thus, the combination of both bioactives
      reduces the effectiveness of each compound to decrease the adipocyte size and
      induce WAT browning.

PMID- 30183291
TI  - Determination of Ionic Hydration Free Energies with Grand Canonical Monte
      Carlo/Molecular Dynamics Simulations in Explicit Water.
AB  - Grand canonical Monte Carlo (GCMC) simulations of ionic solutions with explicit
      solvent models are known to be challenging. One challenge arises from the
      treatment of long-range electrostatics and finite-box size in Monte Carlo
      simulations when periodic boundary condition and Ewald summation methods are
      used. Another challenge is that constant excess chemical potential GCMC
      simulations for charged solutes suffer from inadequate insertion and deletion
      acceptance ratios. In this work, we address those problems by implementing an
      oscillating excess chemical potential GCMC algorithm with smooth particle mesh
      Ewald and finite-box-size corrections to treat the long-range electrostatics. The
      developed GCMC simulation program was combined with GROMACS to perform GCMC/MD
      simulations of ionic solutions individually containing Li+, Na+, K+, Rb+, Cs+, F
      , Cl-, Br-, I-, Ca2+, and Mg2+, respectively. Our simulation results show that
      the combined GCMC/MD approach can approximate the ionic hydration free energies
      with proper treatment of long-range electrostatics. Our developed simulation
      approach can open up new avenues for simulating complex chemical and biomolecular
      systems and for drug discovery.

PMID- 30183292
TI  - Synthesis of Chiral Homoallylic Nitriles by Iridium-Catalyzed Allylation of
      Cyanoacetates.
AB  - A synthesis of chiral homoallylic nitriles by the iridium-catalyzed allylation of
      cyanoacetates followed by Krapcho demethoxycarbonylation has been developed. A
      wide range of homoallylic nitriles were obtained with a high enantioselectivity
      (>95-99% ee). These compounds are useful chiral building blocks because further
      synthetic elaboration starting from a nitrile or terminal alkene is possible.

PMID- 30183293
TI  - Additive-Driven Rhodium-Catalyzed [4+1]/[4+2] Annulations of N-Arylphthalazine
      1,4-dione with alpha-Diazo Carbonyl Compounds.
AB  - A Rh(III)-catalyzed strategy involving the [4+1] annulation of 2-arylphthalazine
      1,4-diones with alpha-diazo carbonyl compounds was developed, accessing a series
      of unprecedented hydroxy-dihydroindazolo-fused phthalazines in good to excellent
      yields. By varying the additive, phthalazino-fused cinnolines were synthesized
      under Rh-catalyzed conditions via [4+2] annulation between the same starting
      materials. Notably, such two strategies showed a good functional group tolerance
      and high atom efficiency.

PMID- 30183294
TI  - Structural Variants of a Liver Fluke Derived Granulin Peptide Potently Stimulate
      Wound Healing.
AB  - Granulins are a family of growth factors involved in cell proliferation. The
      liver-fluke granulin, Ov-GRN-1, isolated from a carcinogenic liver fluke
      Opisthorchis viverrini, can significantly accelerate wound repair in vivo and in
      vitro. However, it is difficult to express Ov-GRN-1 in recombinant form at high
      yield, impeding its utility as a drug lead. Previously we reported that a
      truncated analogue ( Ov-GRN12-35_3s) promotes healing of cutaneous wounds in
      mice. NMR analysis of this analogue indicates the presence of multiple
      conformations, most likely as a result of proline cis/ trans isomerization. To
      further investigate whether the proline residues are involved in adopting the
      multiple confirmations, we have synthesized analogues involving mutation of the
      proline residues. We have shown that the proline residues have a significant
      influence on the structure, activity, and folding of Ov-GRN12-35_3s. These
      results provide insight into improving the oxidative folding yield and
      bioactivity of Ov-GRN12-35_3s and might facilitate the development of a novel
      wound healing agent.

PMID- 30183295
TI  - Copper(II)-Catalyzed Four-Component Oxysulfonylation/Diazenylation: Synthesis of
      alpha-Arylhydrazo-beta-keto Sulfones.
AB  - A new and convenient method for one-pot synthesis of alpha-arylhydrazo-beta-keto
      sulfones is developed via Cu (II)-catalyzed oxysulfonylation/diazenylation of
      alkenes. This four-component cascade reaction enables a series of alpha
      arylhydrazo-beta-keto sulfone derivatives accessed from readily available
      alkenes, sulfinates, and diazonium salts under aerobic conditions. Furthermore,
      the 3-sulfonyl cinnolin-4(1 H)-one skeleton is successfully constructed from the
      corresponding alpha-arylhydrazo-beta-keto sulfone product under basic conditions.

PMID- 30183296
TI  - Structure-Switching Electrochemical Aptasensor for Single-Step and Specific
      Detection of Trace Mercury in Dairy Products.
AB  - A reagentless and single-step electrochemical aptasensor with separation-free
      fashion and rapid response is developed for the Hg2+ assay in dairy products.
      Herein, the sensing strategy is established on Hg2+-induced structural transition
      of the methylene-blue-tagged single-stranded DNA (ssDNA) from a flexible manner
      to rigid hairpin-shaped double-stranded DNA (dsDNA), generating an improved peak
      current for the Hg2+ assay with a detection limit of 0.62 fM. Importantly, the
      best signal-to-noise ratio value can be obtained by exploiting Au flowers as
      sensing material and the optimal ssDNA concentration. The proposed sensor also
      exhibits high selectivity as a result of the specific thymine-Hg2+-thymine (T
      Hg2+-T) coordination chemistry and can be applied to detect Hg2+ in dairy
      products. With the use of the electric "signal-on" switch, the electrochemical
      aptasensor has the advantages of simplicity, ease of operation, and high
      sensitivity and specificity, offering a promising method to assess the safety of
      dairy products polluted with Hg2+.

PMID- 30183297
TI  - Organocatalytic Domino Entry to an Octahydroacridine Scaffold Bearing Three
      Contiguous Stereocenters.
AB  - A facile and enantioselective access to a functionalized octahydroacridine
      scaffold was developed via an organocatalytic domino sequence between
      cyclohexenone and 2- N-substituted benzaldehyde. High levels of yields (up to
      99%) and enantioselectivities (up to 99:1 er) were readily achieved in this
      developed organocatalytic transformation, which holds promising applications in
      the construction of complex multicyclic systems for further pharmacological
      studies.

PMID- 30183298
TI  - Substituting Coumarins for Quinolinones: Altering the Cycloreversion Potential
      Energy Landscape.
AB  - The light-activated cleavage of cyclobutane-based systems via [2 + 2]
      cycloreversions, such as thymine and coumarin dimers, is an important but still
      poorly understood ultrafast photochemical reaction. Systems displaying reversible
      cycloreversion have found various uses in cross-linked polymers, enhancing gas
      adsorption affinities in inorganics, and light-activated medical therapies. We
      report the identification of a heterogeneous mode of cycloreversion for a rarely
      examined coumarin analogue system. Quinolinone monomers and dimers were probed
      using ultraviolet pumped, transient absorption spectroscopy and demonstrated
      radically different photophysical properties than coumarins. Monomers displayed
      enhanced intersystem crossing at almost 1:1 versus the combined nonradiative and
      radiative singlet decay, while the dimers underwent cycloreversion to a one
      excited-one ground state monomer photoproduct pair. The change in both systems
      was directly linked to the lactame group in the quinolinone motif. This discovery
      highlights the dramatic effects that small chemical changes can have on
      photoreaction pathways and opens up a new means to produce and develop more
      efficient cycloaddition-cycloreversion systems.

PMID- 30183299
TI  - Generation of Pairwise Potentials Using Multidimensional Data Mining.
AB  - The rapid development of molecular structural databases provides the chemistry
      community access to an enormous array of experimental data that can be used to
      build and validate computational models. Using radial distribution functions
      collected from experimentally available X-ray and NMR structures, a number of so
      called statistical potentials have been developed over the years using the
      structural data mining strategy. These potentials have been developed within the
      context of the two-particle Kirkwood equation by extending its original use for
      isotropic monatomic systems to anisotropic biomolecular systems. However, the
      accuracy and the unclear physical meaning of statistical potentials have long
      formed the central arguments against such methods. In this work, we present a new
      approach to generate molecular energy functions using structural data mining.
      Instead of employing the Kirkwood equation and introducing the "reference state"
      approximation, we model the multidimensional probability distributions of the
      molecular system using graphical models and generate the target pairwise
      Boltzmann probabilities using the Bayesian field theory. Different from the
      current statistical potentials that mimic the "knowledge-based" PMF based on the
      2-particle Kirkwood equation, the graphical-model-based structure-derived
      potential developed in this study focuses on the generation of lower-dimensional
      Boltzmann distributions of atoms through reduction of dimensionality. We have
      named this new scoring function GARF, and in this work we focus on the
      mathematical derivation of our novel approach followed by validation studies on
      its ability to predict protein-ligand interactions.

PMID- 30183300
TI  - Wavelength-Dependent Exciton-Vibrational Coupling in the Water-Soluble
      Chlorophyll Binding Protein Revealed by Multilevel Theory of Difference
      Fluorescence Line-Narrowing.
AB  - One of the most powerful line-narrowing techniques used to unravel the
      homogeneous lineshapes of inhomogeneously broadened systems is difference
      fluorescence line-narrowing spectroscopy. When this spectroscopy was applied to
      multichromophoric systems so far, the spectra were analyzed by an effective two
      level system approach, composed of the electronic ground state and the lowest
      exciton state. An effective Huang-Rhys factor was assigned for the coupling of
      this state to the vibrations. Here, we extend this approach by including a
      multilevel line shape theory, which takes into account the excitonic coupling
      between pigments and thereby the effect of the delocalization of the excited
      states explicitly. In this way, it becomes possible to extract the spectral
      density of the local exciton-vibrational coupling. The theory is applied to the
      recombinant water-soluble chlorophyll binding protein reconstituted with
      chlorophyll a or b and reveals a significant decrease of the Huang-Rhys factor of
      the local exciton-vibrational coupling with decreasing transition energy of the
      chlorophylls. This decrease could be due to the increase in steric interactions
      reducing the flexibility of the environment and red-shifting the site energy of
      the pigments.

PMID- 30183301
TI  - Electronic Spectroscopies Combined with Quantum Chemistry Calculations: Study of
      the Interactions of 3-Hydroxyflavone with Copper Ions.
AB  - The current study aims at obtaining a better understanding of the mechanisms
      involved in the complexation of copper ions by 3-hydroxyflavone (3HF), which is
      one of the most studied compounds of the flavonoid family. To achieve this goal,
      quantum chemistry calculations combined with electronic spectroscopies, including
      absorption, fluorescence emission, and excitation, have been used. The formation
      of successive complexes of stoichiometry (metal/ligand) 1:2, 1:1, and 3:2 has
      been highlighted. Even under acidic conditions (pH = 4.0), the alpha-hydroxy-keto
      function of the molecule presents a high complexing power with regard to copper
      ions, insofar as a stable complex of 1:2 stoichiometry is obtained with a large
      conditional stability constant (log beta = 8.7). The formation of this
      predominant species induces a quenching of the dual fluorescence of 3HF, whereas
      the second complex of stoichiometry 1:1 presents a fluorescence emission.

PMID- 30183302
TI  - Pickering Emulsion Stabilized by Microporous Organic Polymer Particles for the
      Fabrication of a Hierarchically Porous Monolith.
AB  - A hierarchically porous monolith comprising the melamine-based microporous
      organic polymer (MOP) particles was prepared by the Pickering emulsion templating
      method. The MOP particles were synthesized by polycondensation of melamine and
      terephthaldicarboxaldehyde. Because of the balanced presence of hydrophilic
      nitrogen containing groups and hydrophobic benzene rings, the MOP particles
      showed good amphiphilicity. A Pickering emulsion was prepared, where cyclohexane
      droplets with an average size of about 25 MUm were stabilized by the MOP
      particles (3.4 wt %) in an aqueous continuous phase. The cyclohexane internal
      phase fraction was slightly higher than 60%. The emulsion showed no phase
      separation even after two weeks. The Pickering emulsion containing a small amount
      of polyvinyl alcohol (1 wt %) in a continuous phase as a reinforcement was used
      as a template for the fabrication of a monolith of the MOP particles. The
      Pickering emulsion was freeze-dried to produce a hierarchically porous monolith.
      The MOP monolith possessed macropores templated by the oil droplets and micro-
      and mesopores in the MOP particles that constituted the macropore walls. The MOP
      monolith exhibited a high dye absorption ability in a solution of RhB in
      chloroform and a good absorption capacity for nonpolar organic solvents. After
      the absorption, the monolith could be regenerated by solvent exchange with
      cyclohexane and subsequent freeze-drying.

PMID- 30183303
TI  - Clearly Detectable, Kinetically Restricted Solid-Solid Phase Transition in cis
      Ceramide Monolayers.
AB  - Sphingosine [(2 S,3 R,4 E)-2-amino-4-octadecene-1,3-diol] is the most common
      sphingoid base in mammals. Ceramides are N-acyl sphingosines. Numerous small
      variations on this canonical structure are known, including the 1-deoxy, the 4,5
      dihydro, and many others. However, whenever there is a Delta4 double bond, it
      adopts the trans (or E) configuration. We synthesized a ceramide containing 4 Z
      sphingosine and palmitic acid ( cis-pCer) and studied its behavior in the form of
      monolayers extended on an air-water interface. cis-pCer acted very differently
      from the trans isomer in that, upon lateral compression of the monolayer, a solid
      solid transition was clearly observed at a mean molecular area <=44 A2.molecule
      1, whose characteristics depended on the rate of compression. The solid-solid
      transition, as well as states of domain coexistence, could be imaged by atomic
      force microscopy and by Brewster-angle microscopy. Atomistic molecular dynamics
      simulations provided results compatible with the experimentally observed
      differences between the cis and trans isomers. The data can help in the
      exploration of other solid-solid transitions in lipids, both in vitro and in
      vivo, that have gone up to now undetected because of their less obvious change in
      surface properties along the transition, as compared to cis-pCer.

PMID- 30183304
TI  - Dynamic Interaction between a Millimeter-Sized Bubble and Surface Microbubbles in
      Water.
AB  - The coalescence between microbubbles and millimeter-sized bubbles is an
      elementary process in various industrial applications such as froth flotation and
      wastewater treatment. Fundamental understanding of the coalescence behavior
      between two colliding bubbles requires knowledge of water drainage from the thin
      liquid film between the deformable air-water surfaces, a simple phenomenon with
      high complexity in physics because of the interplay of surface forces,
      hydrodynamic drainage, and surface rheology. In this work, we performed
      simultaneous measurements of the interaction force and spatial thin-film
      thickness during the collision between a millimeter-sized bubble (radius 1.2 mm)
      and surface microbubbles (radii between 30 and 700 MUm) using our recently
      developed dynamic force apparatus. The interaction force during the collision
      agrees well with the prediction from the Stokes-Reynolds-Young-Laplace model with
      the tangentially immobile boundary condition at the air-liquid interface.
      However, the measured coalescence times for different bubble sizes are shorter
      than the model predictions, possibly caused by a rapid drainage behavior along
      with the loss of symmetry of the thin liquid film. In dozens of experimental
      runs, the bubbles coalesced at a critical film thickness of 25 +/- 15 nm, which
      agrees reasonably well with the predicted rupture thickness using attractive van
      der Waals interaction force. These results suggest that the nonsymmetric drainage
      process, rather than the rupture thickness, contributes to the scattering of the
      experimental coalescence time between two fast-colliding air bubbles.
      Furthermore, our results suggest that smaller surface bubbles (30-100 MUm) are
      more effective for the attachment onto a large bubble as the coalescence time
      decreases considerably when the microbubbles are smaller than 100 MUm.

PMID- 30183305
TI  - Does the Enthalpy of Heterogeneous Chemical Reactions Affect the Formation of
      Aqueous Secondary Organic Aerosols?
AB  - The chemical aging of liquid organic aerosols most likely occurs via exothermic
      heterogeneous chemical reactions on the aerosol's surface. Because of the
      enthalpy of reactions, the temperature of an aerosol particle during its chemical
      aging may become greater than the ambient (air) temperature. We attempt to shed
      light on this aspect of the formation of secondary organic aerosols considering
      their nucleation and chemical aging as concomitant processes. Using the model of
      aqueous hydrophilic-hydrophobic organic aerosols in the framework of classical
      nucleation theory, we evaluate characteristic time scales of the four most
      important processes involved in this complex phenomenon. Their analysis suggests
      that the release of the enthalpy of heterogeneous chemical reactions during the
      chemical aging of organic aerosols may play a significant impeding role in the
      formation of an ensemble of aqueous secondary organic aerosols via nucleation and
      hence must be taken into account in atmospheric aerosol and global climate
      models.

PMID- 30183307
TI  - The Roles of Fatty-Acid Modification in the Activity of the Anticancer Peptide R
      Lycosin-I.
AB  - We previously reported that R-lycosin-I, modified by amino acid substitution from
      lycosin-I, was a peptide with anticancer activity and a linear amphipathic alpha
      helix conformation and that it can induce cancer cell apoptosis and inhibit cell
      proliferation. However, the anticancer activity of R-lycosin-I was not highly
      improved. In order to further improve the anticancer activity of R-lycosin-I,
      fatty acids with different chain lengths from 12 to 20 carbons were introduced to
      the N-terminal of R-lycosin-I to yield five lipopeptides (R-C12, R-C14, R-C16, R
      C18, R-C20). The physicochemical properties of the five lipopeptides were
      determined by hydrodynamic size, zeta-potential, and circular dichroism
      spectroscopy, respectively. Then, the cytotoxic activity of these lipopeptides in
      A549 cells was evaluated with serum-containing and serum-free media,
      respectively, showing their anticancer activities were all increased through
      fatty-acid modification. This may be a result of the increased hydrophobicity and
      the enhanced interaction with the cancer cell membrane. The cytotoxic activity of
      R-C16 was 3-4-fold higher than that of the original R-lycosin-I and also was the
      strongest among all five lipopeptides, whether in serum or serum-free conditions.
      Compared with R-lycosin-I, the lactate dehydrogenase (LDH) leakage assay and
      scanning electron microscopy (SEM) indicated that R-C16 had a weakly destructive
      effect on the cancer cell membrane, but it might cause apoptosis to exert an
      anticancer activity. Finally, the impacts of fatty-acid length on the
      physicochemical properties and the anticancer potential of peptide were
      discussed. Our data consolidate work on fatty-acid-modified anticancer peptides.

PMID- 30183306
TI  - Solution-Processed Bi2S3 Photoresistor Film To Mitigate a Trade-off between
      Morphology and Electronic Properties.
AB  - Bismuth sulfide (Bi2S3) is an attractive 2D layered, visible-light-absorbing
      semiconductor composed of nontoxic, abundant elements. Improving the quality of a
      Bi2S3 film for device applications while maintaining its intrinsic electronic
      properties is a challenge, as conventional film fabrication processes require a
      trade-off due to the uncontrolled nucleation and growth steps. We report a novel
      procedure for Bi2S3 film formation involving spin-coating of a precursor solution
      of bismuth acetate and thiourea, followed by crystallization under diluted H2S
      gas. This two-step process produced a large-grained (<400 nm), smooth (surface
      roughness = 1.7 nm), and highly pure Bi2S3 film with a layer-stacked structure on
      a substrate. Most importantly, the film exhibited a moderate Hall effect electron
      mobility (~7 cm2 V-1 s-1) and excellent performance as a photoresistor with
      improved photoconductance and on-off ratio compared with those prepared by
      conventional methods. Our approach provides a versatile route for the development
      of metal sulfide semiconductors for optoelectronic devices.

PMID- 30183308
TI  - Palmitate-Induced Insulin Hypersecretion and Later Secretory Decline Associated
      with Changes in Protein Expression Patterns in Human Pancreatic Islets.
AB  - In obese children with high circulating concentrations of free fatty acid
      palmitate, we have observed that insulin levels at fasting and in response to a
      glucose challenge were several times higher than in obese children with low
      concentrations of the fatty acid as well as in lean controls. Declining and even
      insufficient insulin levels were observed in obese adolescents with high levels
      of the fatty acid. In isolated human islets exposed to palmitate we have observed
      insulin hypersecretion after 2 days exposure. In contrast, insulin secretion from
      the islets was reduced after 7 days culture in the presence of the fatty acid.
      This study aims at identifying islet-related biological events potentially linked
      with the observed insulin hypersecretion and later secretory decline in these
      obese children and adolescents using the islet model. We analyzed protein
      expression data obtained from human islets exposed to elevated palmitate levels
      for 2 and 7 days by an improved methodology for statistical analysis of
      differentially expressed proteins. Protein profiling of islet samples by liquid
      chromatography-tandem mass spectrometry identified 115 differentially expressed
      proteins (DEPs). Several DEPs including sorcin were associated with increased
      glucose-stimulated insulin secretion in islets after 2 days of exposure to
      palmitate. Similarly, several metabolic pathways including altered protein
      degradation, increased autophagy, altered redox condition, and hampered insulin
      processing were coupled to the functional impairment of islets after 7 days of
      culture in the presence of palmitate. Such biological events, once validated in
      the islets, may give rise to novel treatment strategies aiming at normalizing
      insulin levels in obese children with high palmitate levels, which may reduce or
      even prevent obesity-related type 2 diabetes mellitus.

PMID- 30183309
TI  - Interfacial Behavior of Recombinant Spider Silk Protein Parts Reveals Cues on the
      Silk Assembly Mechanism.
AB  - The mechanism of silk assembly, and thus the cues for the extraordinary
      properties of silk, can be explored by studying the simplest protein parts needed
      for the formation of silk-like materials. The recombinant spider silk protein
      4RepCT, consisting of four repeats of polyalanine and glycine-rich segments
      (4Rep) and a globular C-terminal domain (CT), has previously been shown to
      assemble into silk-like fibers at the liquid-air interface. Herein, we study the
      interfacial behavior of the two parts of 4RepCT, revealing new details on how
      each protein part is crucial for the silk assembly. Interfacial rheology and
      quartz crystal microbalance with dissipation show that 4Rep interacts readily at
      the interfaces. However, organized nanofibrillar structures are formed only when
      4Rep is fused to CT. A strong interplay between the parts to direct the assembly
      is demonstrated. The presence of either a liquid-air or a liquid-solid interface
      had a surprisingly similar influence on the assembly.

PMID- 30183310
TI  - Ideal Inner Nodal Chain Semimetals in Li2XY (X = Ca, Ba; Y = Si, Ge) Materials.
AB  - The chain-type nodal loops in the reciprocal space can generate exotic nodal
      chain fermions. Here, we report that Li2XY (X = Ca, Ba; Y = Si, Ge) compounds are
      ideal inner nodal chain semimetals. Their band structures are composed of two
      connecting nodal loops with either hybrid or type-I band dispersion. The
      signatures of the nodal chain, such as the nontrivial surface states, are quite
      pronounced in these Li2XY compounds, since there is only a single inner nodal
      chain without other extraneous bands near the Fermi level. These compounds are
      existing materials and ambient-stable, which is available to realize the
      experimental detection of inner nodal chain fermions or further the practical
      applications.

PMID- 30183311
TI  - Excited-State Spectra of Strongly Correlated Molecules from a Reduced-Density
      Matrix Approach.
AB  - Excited-state energies are computed in the space of single-electron transitions
      from the ground state from only a knowledge of the two-electron reduced density
      matrix (2-RDM). Previous work developed and applied the theory to small molecular
      systems with accurate results, but applications to both larger and more
      correlated molecules were hindered by ill-conditioning of the effective
      eigenvalue problem. Here we improve the excited-spectra 2-RDM theory through a
      stable Hamiltonian-shifted regularization algorithm that removes the near
      singularities within the computation. The theory with ground-state 2-RDMs from
      the variational 2-RDM method is applied to the excited energies of strongly
      correlated molecules including the optical band gap of hydrogen and acene chains,
      the singlet-triplet splitting of nickel dithiolates, as well as the low-lying
      excited states of an optical dye. While single-excitation theories like CISD and
      TD-DFT underestimate band gaps and excited-state splittings, the 2-RDM theory
      yields band gap and excited-state splittings that are in good agreement with full
      configuration interaction and experiment where available.

PMID- 30183312
TI  - Melanin Precursor Influence on Structural Colors from Artificial Melanin
      Particles: PolyDOPA, Polydopamine, and Polynorepinephrine.
AB  - Polydopamine (PDA) is of interest as a mimetic material of melanin to produce
      structural color materials. Herein, to investigate the influence of the material
      composition of the artificial melanin particles on structural color, we
      demonstrated the preparation of core-shell particles by polymerization of
      norepinephrine or 3,4-dihydroxyphenylalanine, which are melanin precursors
      similar to dopamine, in the presence of polystyrene particles. It was revealed
      that the arrays of the prepared particles produce high-visibility structural
      color because of absorption of scattering light. Although poly(3,4
      dihydroxyphenylalanine) showed the same tendency as PDA which was previous
      studied, polynorepinephrine can easily produce a smooth and thick shell layer
      compared with that of PDA, and pellets consisting of the particles showed angle
      dependent structural color. Therefore, the artificial melanin particles that
      produce angle-dependent structural color became stable than ever before. These
      results indicated that material compositions of artificial melanin particles have
      influence on structural color, and an important finding for application as a
      coloring material was obtained.

PMID- 30183313
TI  - Effects of Vancomycin and Ciprofloxacin on the NMRI Mouse Metabolism.
AB  - The reduction in gut microbiota diversity is associated with a range of human
      diseases. Overuse of antibiotics has been associated with a diminished gut
      microbial diversity in humans and may promote microbiota-associated negative
      effects to physical health, such as the metabolic syndrome-cluster of diseases
      and mental illnesses. There is a pressing need to deepen the understanding of the
      effects of antibiotics at the biochemical level. The current study investigated
      metabolic effects of two widely prescribed antibiotics-vancomycin and
      ciprofloxacin-on biofluids and brain tissue samples of NMRI female mice using a
      1H nuclear magnetic resonance (NMR) spectroscopy-based metabolic profiling
      approach. While both antibiotics significantly affected the host metabolic
      signatures of urine and feces, only ciprofloxacin induced metabolic changes in
      plasma. Metabolic perturbations were pronounced 1 day post-treatment, reverting
      back to baseline at day 20 post-treatment. Both antibiotics induced changes in
      the choline metabolism, host-microbial cometabolites, short chain fatty acid
      production, and protein/purine degradation. The metabolic profiles of brain
      tissue aqueous extracts did not show any antibiotics-related changes by day 20
      post-treatment. The data suggest that the metabolic disruptions in biofluids
      caused by antibiotics are reversed by day 20 post-treatment when compared to the
      pre-treatment profiles.

PMID- 30183314
TI  - Anomalous Wetting of Underliquid Systems: Oil Drops in Water and Water Drops in
      Oil.
AB  - We have investigated the wetting phenomena of two underliquid systems, i.e., oil
      (drop) in water medium and water (drop) in oil medium for two different
      substrates, poly(methyl methacrylate) (PMMA) and glass. We have conducted
      detailed static (equilibrium) and dynamic contact angle measurements of drops on
      substrates kept in air, water, and oils of varying densities, viscosities, and
      surface tensions. We compared the experimentally observed contact angles with
      those predicted by the conventional wetting theories, namely, Young's equation
      and the Owens and Wendt approach. The results reported herein showed that
      experimental values vary in the range of 8-20% with the conventional theoretical
      model for water (drop) in oil (viscous surrounding medium) on PMMA substrate.
      However, oil (drop) in water medium on PMMA does not show such an anomaly. By
      taking into consideration a thin oil film between a water drop and PMMA
      originating from the surrounding oil medium, the modified Young's equation is
      proposed here. We found that the percentage difference between experimentally
      observed contact angles with modified Young's equation is in the range of 0.88
      5.88%, which is very less compared to percentage difference with classic Young's
      equation. For glass substrates, the standard Young's equation does not translate
      to the underliquid systems whereas the Owens and Wendt theory could not correctly
      predict the underliquid contact angles. However, the modified Young's equation
      with thin-film consideration agrees very well with the experimental values and
      thereby demonstrated the presence of a thin film between a drop and glass
      substrate originating from the surrounding viscous medium. This present
      experimental study coupled with detailed theoretical analyses demonstrates the
      anomalous wetting signature of drops on substrates submerged in surrounding
      viscous medium, which is very different from the reported studies for drops on
      substrates kept in air (inviscid medium).

PMID- 30183315
TI  - Palladium-Catalyzed Enantioselective Csp3-Csp3 Cross-Coupling for the Synthesis
      of (Poly)fluorinated Chiral Building Blocks.
AB  - A general method for the enantioselective synthesis of carbo- and heterocyclic
      carbonyl compounds bearing fluorinated alpha-tetrasubstituted stereocenters using
      palladium-catalyzed decarboxylative allylic alkylation is described. The
      stereoselective Csp3-Csp3 cross-coupling reaction delivers five- and six-membered
      ketone and lactam products bearing (poly)fluorinated tetrasubstituted chiral
      centers in high yields and enantioselectivities. These fluorinated,
      stereochemically rich building blocks hold potential value in medicinal chemistry
      and are prepared using an orthogonal and enantioselective approach into such
      chiral moieties compared to traditional approaches, often without the use of
      electrophilic fluorinating reagents.

PMID- 30183316
TI  - Palladium-Catalyzed anti-Selective Fluoroalkylboration of Internal and Terminal
      Alkynes.
AB  - A Pd-catalyzed anti-stereospecific alkyne fluoroalkylboration, including mono-,
      di-, and perfluoroalkylboration, has been developed with fluoroalkyl halides and
      diboron reagents. The reaction is effective for both internal and terminal
      alkynes. It provides straightforward and streamlined access to functionalized 1,2
      fluoroalkylboronated alkenes in a highly regio- and stereocontrolled manner.
      Preliminary studies suggest that this reaction is enabled by the combination of
      radical alkylation and metal-catalyzed borylation, thus leading to the
      realization of three-component trans-carboboration of alkynes for the first time.

PMID- 30183317
TI  - Copper-Catalyzed Asymmetric Addition of Tertiary Carbon Nucleophiles to 2 H
      Azirines: Access to Chiral Aziridines with Vicinal Tetrasubstituted
      Stereocenters.
AB  - A catalytic asymmetric nucleophilic addition of tertiary carbon nucleophiles to 2
      H-azirines was established in the presence of the chiral N,N'-dioxide/CuII
      complex. Various chiral aziridines with vicinal tetrasubstituted stereocenters
      were obtained in high yields with excellent diastereoselectivities and
      enantioselectivities. Moreover, on the basis of the control experiments, X-ray
      structures of the products, and catalyst, a possible transition state was
      proposed to explain the stereoselectivity.

PMID- 30183318
TI  - Redox-Neutral Synthesis of Selenoesters by Oxyarylation of Selenoalkynes under
      Mild Conditions.
AB  - An approach for the mild synthesis of selenoesters starting from selenoalkynes
      through an acid-catalyzed, redox-neutral oxyarylation reaction is reported.
      Bronsted acid activation of a selenoalkyne leads to a selenium-stabilized vinyl
      cation, which is captured by an aryl sulfoxide and undergoes sigmatropic
      rearrangement to deliver the final alpha-arylated selenoester product.
      Computational studies have been carried out to elucidate the nature of the Se
      stabilized carbocation.

PMID- 30183319
TI  - Palladium-Catalyzed Dual C(sp2)-H Functionalization of Indole-2-carboxamides
      Involving a 1,2-Acyl Migration: A Synthesis of Indolo[3,2- c]quinolinones.
AB  - A novel Pd/Cu catalytic system to construct indolo[3,2- c]quinolinones has been
      developed starting from indole-2-carboxamides. Substrates were transformed into
      indolo[3,2- c]quinolinones through dual C(sp2)-H functionalization of the indole
      moiety and arene, in which a carbonyl 1,2-migration was involved. The
      corresponding products were obtained in moderate to excellent yields with a wide
      substrate scope.

PMID- 30183321
TI  - Downregulation of microRNA-149 in retinal ganglion cells suppresses apoptosis
      through activation of the PI3K/Akt signaling pathway in mouse with glaucoma.
AB  - Glaucoma represents a major cause of blindness, generally associated with
      elevated intraocular pressure (EIOP). The aim of the present study was to
      investigate whether microRNA-149 (miR-149) affects retinal ganglion cells (RGCs)
      and the underlying mechanism based on a mouse model of chronic glaucoma with
      EIOP. The successfully modeled mice were administered with mimics or inhibitors
      of miR-149. Next, the number of RGCs, ultrastructural changes of RGCs, and purity
      of RGCs in the retinal tissues were detected. Moreover, the RGCs were collected
      and subsequently treated with 60 mmHg pressure, and transfected with a series of
      plasmids aiding in the regulation of the expression of miR-149 and betacellulin
      (BTC). The levels of miR-149, BTC, PI3K, and Akt were subsequently determined.
      Finally, RGC viability and apoptosis were detected accordingly. Dual luciferase
      reporter gene assay provided validation, highlighting BTC was indeed a target
      gene of miR-149. The downregulation of miR-149 is accompanied by an increased
      number of RGCs and decreased ultrastructural RGC alterations. Additionally,
      downregulated miR-149 was noted to increase the levels of BTC, PI3K, and Akt in
      both the retinal tissues and RGCs, while the silencing of miR-149 was observed to
      promote the viability of RGC and inhibit RGC apoptosis. Taken together, the
      results of the current study provided validation suggesting that the
      downregulation of miR-149 confers protection to RGCs by means of activating the
      PI3K/Akt signaling pathway via upregulation of BTC in mouse with glaucoma.
      Evidence presented indicated the promise of miR-149 inhibition as a potential
      therapeutic strategy for glaucoma treatment.

PMID- 30183322
TI  - Mixing and delivery of multiple controlled oxygen environments to a single
      multiwell culture plate.
AB  - Precise oxygen control is critical to evaluating cell growth, molecular content
      and stress-response in cultured cells. We have designed, fabricated and
      characterized a 96-well plate-based device that is capable of delivering eight
      static or dynamically changing oxygen environments to different rows on a single
      plate. The device incorporates a gas mixing tree that combines two input gases to
      generate the eight gas mixtures that supply each row of the plate with a
      different gas atmosphere via a removable manifold. Using air and nitrogen as feed
      gases, a single 96-well plate can culture cells in applied gas atmospheres
      ranging from pO2 levels ranging from 1 to 135 mmHg. Human cancer cell lines MCF
      7, PANC-1 and Caco-2 were grown on a single plate under this range of oxygen
      levels. Only cells grown in wells exposed to pO2 <=37 mmHg express the endogenous
      hypoxia markers HIF-1alpha and carbonic anhydrase IX. This design is amenable to
      multiwell plate-based molecular assays or drug dose-response studies in static or
      cycling hypoxia conditions.

PMID- 30183320
TI  - Ultra-Performance Liquid Chromatography-High-Resolution Mass Spectrometry and
      Direct Infusion-High-Resolution Mass Spectrometry for Combined Exploratory and
      Targeted Metabolic Profiling of Human Urine.
AB  - The application of metabolic phenotyping to epidemiological studies involving
      thousands of biofluid samples presents a challenge for the selection of
      analytical platforms that meet the requirements of high-throughput precision
      analysis and cost-effectiveness. Here direct infusion-nanoelectrospray (DI-nESI)
      was compared with an ultra-performance liquid chromatography (UPLC)-high
      resolution mass spectrometry (HRMS) method for metabolic profiling of an
      exemplary set of 132 human urine samples from a large epidemiological cohort.
      Both methods were developed and optimized to allow the simultaneous collection of
      high-resolution urinary metabolic profiles and quantitative data for a selected
      panel of 35 metabolites. The total run time for measuring the sample set in both
      polarities by UPLC-HRMS was 5 days compared with 9 h by DI-nESI-HRMS. To compare
      the classification ability of the two MS methods, we performed exploratory
      analysis of the full-scan HRMS profiles to detect sex-related differences in
      biochemical composition. Although metabolite identification is less specific in
      DI-nESI-HRMS, the significant features responsible for discrimination between
      sexes were mostly the same in both MS-based platforms. Using the quantitative
      data, we showed that 10 metabolites have strong correlation (Pearson's r > 0.9
      and Passing-Bablok regression slope of 0.8-1.3) and good agreement assessed by
      Bland-Altman plots between UPLC-HRMS and DI-nESI-HRMS and thus can be measured
      using a cheaper and less sample- and time-consuming method. A further twenty
      metabolites showed acceptable correlation between the two methods with only five
      metabolites showing weak correlation (Pearson's  r < 0.4) and poor agreement due
      to the overestimation of the results by DI-nESI-HRMS.

PMID- 30183323
TI  - Lung Microbiome is Influenced by the Environment and Asthmatic Status in an
      Equine Model of Asthma.
AB  - RATIONALE: There is evidence that lung microbiome differs between asthmatic and
      healthy humans, but the effect of environmental conditions and medication is
      unknown and difficult to study. Equine asthma is a naturally occurring chronic
      airway disease characterized by reversible airway inflammation and
      bronchoconstriction upon exposure to inhaled antigens. OBJECTIVES: To evaluate
      the effect that environmental conditions and disease status have on pulmonary,
      nasal and oral microbiome. METHODS: Six asthmatic and 6 healthy horses were
      studied while at pasture ("low antigen exposure"), when being housed indoors and
      fed good quality hay ("moderate exposure"), and poor quality hay ("high
      exposure"). At each time point, lung function was recorded, bronchoalveolar
      lavage, oral and nasal rinses were collected, and 16S rRNA gene sequencing
      performed. MEASUREMENTS AND MAIN RESULTS: Asthmatic horses developed airway
      obstruction and inflammation under "moderate" and "high antigen exposure"
      conditions, while non-asthmatic horses showed mild inflammation under "high
      antigen exposure", without bronchoconstriction. Lung, oral and nasal communities
      clustered by environmental condition, but only lung communities were different
      between healthy and asthmatic horses. The association between asthma and lung
      microbiome was strongest in horses under "moderate antigen exposure".
      CONCLUSIONS: Pulmonary, oral and nasal microbiome are influenced by environmental
      conditions, but only the pulmonary microbiome differs between horses with and
      without asthma. This difference, mainly present when airway inflammation was
      present in horses with asthma but not in controls, suggests that the altered lung
      microbiome in asthma might not be inherent but coincident with inflammation.

PMID- 30183324
TI  - Optimal antero-posterior position of the maxillary central incisors and its
      relationship to the forehead in adult African American females.
AB  - OBJECTIVES:: To determine an optimal anteroposterior (AP) position of the
      maxillary central incisors and their relationship to the forehead in adult
      African American (AA) females. MATERIALS AND METHODS:: Smile profile photographs
      of 150 AA females were acquired and divided into an optimal control group (N =
      48) and a study group (N = 102) based on the position of the maxillary central
      incisors, as judged by a panel of orthodontists and orthodontic residents. The AP
      position of the maxillary central incisors and the forehead inclination (FI) were
      measured relative to Glabella vertical (GV). A two-sample t-test was used to
      compare the incisor AP position and the FI between the two groups. Linear
      regression was used to quantify the relationship between the incisor AP position
      and the FI. RESULTS:: In all groups, the maxillary incisors were anterior to GV.
      However, a significant difference was found in the incisor AP position between
      the groups (8.58 +/- 3.96 mm for the control group and 11.2 +/- 4.48 mm for the
      study group; P = .001). Furthermore, the control group demonstrated a positive
      association between the optimal AP position of the maxillary central incisors and
      FI ( P < .0001). CONCLUSIONS:: GV is a reliable landmark with which to access the
      AP maxillary incisor position in AA females. The optimal AP position of the
      maxillary central incisors is significantly associated with FI; the greater the
      FI, the more anterior the optimal maxillary incisor position. A prediction
      equation to determine the optimal position of the maxillary incisors relative to
      GV for AA females is proposed.

PMID- 30183325
TI  - The Effects of IFN-lambda on Epithelial Barrier Function Contribute to K.
      pneumoniae ST258 Pneumonia.
AB  - IFN-lambda and IL-22, cytokines that share the co-receptor IL-10RB, are both
      induced over the course of Klebsiella pneumoniae ST258 (KP35) pneumonia. IL-22 is
      known to protect mucosal barriers whereas the effects of IFN-lambda on the mucosa
      are not established. We postulated that IFN-lambda plays a role in regulating the
      airway epithelial barrier to facilitate cellular trafficking to the site of
      infection. In response to IFN-lambda the transmigration of neutrophils across a
      polarized monolayer of airway epithelial cells was increased, consistent with
      diminished epithelial integrity. KP35 infection increased epithelial permeability
      and pretreatment with IFN-lambda amplified this effect and facilitated bacterial
      transmigration. These effects of IFN-lambda were confirmed in vivo, in that mice
      lacking the receptor for IFN-lambda (Ifnlr1-/-), were protected from bacteremia
      in a murine model of KP35 pneumonia. Conversely, the integrity of the epithelial
      barrier was protected by IL-22 with subsequent impairment of neutrophil and
      bacterial transmigration in vitro. Maximal expression of IL-22 in vivo was later
      in the course of infection than IFN-lambda production with high levels of IL-22
      produced by recruited immune cells at 48 hours consistent with a role in
      epithelial barrier recovery. The divergent and opposing expression of these two
      related cytokines suggest a regulated interaction in the host response to KP35
      infection. A major physiological effect of IFN-lambda signaling is in decreasing
      epithelial barrier integrity, which facilitates immune cell recruitment but also
      enables K. pneumoniae invasion.

PMID- 30183326
TI  - Development and Function of Uterine Glands in Domestic Animals.
AB  - All mammalian uteri contain glands that synthesize or transport and secrete
      substances into the uterine lumen. Uterine gland development, or adenogenesis, is
      uniquely a postnatal event in sheep and pigs and involves differentiation of
      glandular epithelium from luminal epithelium, followed by invagination and
      coiling morphogenesis throughout the stroma. Intrinsic transcription factors and
      extrinsic factors from the ovary and pituitary as well as the mammary gland
      (lactocrine) regulate uterine adenogenesis. Recurrent pregnancy loss is observed
      in the ovine uterine gland knockout sheep, providing unequivocal evidence that
      glands and their products are essential for fertility. Uterine gland hyperplasia
      and hypertrophy during pregnancy are controlled by sequential actions of hormones
      from the ovary and/or pituitary as well as the placenta. Gland-derived histotroph
      is transported by placental areolae for fetal growth. Increased knowledge of
      uterine gland biology is expected to improve pregnancy outcomes, as well as the
      health and productivity of mothers and their offspring. Expected final online
      publication date for the Annual Review of Animal Biosciences Volume 7 is February
      15, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for
      revised estimates.

PMID- 30183327
TI  - Inpatient Pediatric Epistaxis: Management and Resource Utilization.
AB  - OBJECTIVES: Epistaxis is a common condition that rarely warrants hospital
      admission in the pediatric population, making its inpatient management difficult
      to study. This study aims to use a nationwide database to analyze trends in the
      treatment of pediatric patients admitted with epistaxis and determine factors
      impacting total charges. METHODS: The latest (2012) version of the Kids'
      Inpatient Database (KID), Healthcare Cost and Utilization Project (HCUP), Agency
      for Healthcare Research and Quality was used to identify weighted discharges with
      the primary diagnosis of epistaxis. Information regarding demographics,
      comorbidities, treatment, hospital burden, and other admission details were
      obtained. Linear regression was used to analyze factors suspected to increase
      cost. RESULTS: Among 372 weighted discharges, the mean age was 9.68 years (SD =
      5.79), and 60.0% were male. The most common comorbidities were thrombocytopenia,
      von Willebrand disease, and chronic sinusitis. The majority of admissions with
      epistaxis (56.7%) did not undergo any procedure to control epistaxis. Mean total
      charges was $30 208 (SD = $62 683) with a mean length of stay of 2.46 days (SD =
      3.31). Independent predictors of increased charges included longer length of
      stay, admission from the emergency department, and median household income within
      the third quartile for patients' ZIP codes. Midwest hospital region independently
      predicted decreased charges. Having a procedure to control epistaxis did not
      significantly impact cost. CONCLUSIONS: Pediatric epistaxis admissions often do
      not require long hospital stays or procedural control of the bleed. However,
      significant charges are incurred treating epistaxis. Awareness of factors
      impacting these charges can potentially improve resource utilization.

PMID- 30183328
TI  - Maternal Asthma, Pregnancy Complications and Offspring Wheeze: Untangling the
      Web.

PMID- 30183329
TI  - Auricular Acupressure Improves Habit Reversal Treatment for Nail Biting.
AB  - OBJECTIVE: Nail biting leads to a variety of health issues. Habit reversal
      treatment is a major approach to cease nail biting, but is often ineffective
      since patients continue to suffer from anxiety, a major trigger. This study
      investigated whether the potential anxiety relief provided by auricular
      acupressure could improve the efficacy of habit reversal treatment, as evidenced
      by improved stomatological and other outcomes. METHODS: In a pragmatic,
      randomized, crossover, pilot clinical trial, 83 nail biters (8-12 years old)
      received habit reversal treatment in combination with either auricular
      acupressure intended to reduce anxiety (Method A) or placebo auricular
      acupressure (Method B). The alternative protocol was employed after a two-month
      washout period. The primary outcome measured was the 41-item child self-reported
      version of the Screen for Child Anxiety Related Emotional Disorders, while the
      secondary outcomes were the nail growth status (NS), which represented the
      fingernail growth of each finger during habit reversal treatment, simplified
      plaque index (SPI), and the simplified gingival index (SGI) as measures of oral
      health. A paired sample t-test was used to assess the differences between Methods
      A and B, and the differences in the anxiety scores, NS, SGI, and SPI between the
      baseline and each time point. RESULTS: Forty-one children successfully completed
      both arms of the treatments and attended all appointments. There were significant
      differences in the efficacy of habit reversal treatment, the anxiety score, the
      nail status, and the SGI in favor of Method A (p < 0.001). CONCLUSION: Auricular
      acupressure appears to improve the efficacy of habit reversal treatment, likely
      by reducing anxiety.

PMID- 30183331
TI  - Controlling for Obesity in Obstructive Sleep Apnea. Results from Dynamic Magnetic
      Resonance Imaging.

PMID- 30183330
TI  - Impairment of Fatty Acid Oxidation in Alveolar Epithelial Cells Mediates Acute
      Lung Injury.
AB  - Profound impairment in cellular oxygen consumption, named cytopathic dysoxia, is
      one of the pathological hallmarks in the lungs of patients with pathogen-induced
      acute lung injury (ALI). However, the underlying mechanism for this functional
      defect remains largely unexplored. In this study, we found that primary mouse
      alveolar epithelial cells (AECs) conducted robust fatty acid oxidation (FAO).
      More importantly, FAO was strikingly impaired in AECs of mice with
      lipopolysaccharide (LPS) induced ALI. The metabolic deficiency in these cells was
      likely due to decreased expression of key mediators involved in FAO and
      mitochondrial bioenergenesis, such as PGC-1alpha, CPT1A and MCAD. We found that
      treatment of alveolar epithelial line MLE-12 cells with bronchoalveolar lavage
      fluids (BALFs) from mice with ALI decreased FAO and this effect was largely
      replicated in MLE-12 cells treated with pro-inflammatory cytokine TNF-alpha,
      which was consistent with downregulations of PGC-1alpha, CPT1A, LCAD and MCAD in
      the same treated cells. Furthermore, we found that the BALFs from ALI mice and
      TNF-alpha inhibited MLE-12 bioenergenesis and promoted cell apoptosis. In
      delineation of the role of FAO in ALI in vivo, we found that conditional ablation
      of AEC PGC-1alpha aggravated LPS induced ALI. In contrast, fenofibrate, an
      activator of the PPAR-alpha/ PGC-1alpha cascade, protected mice from this
      pathology. In summary, these data suggest that FAO is essential to AEC
      bioenergenesis and functional homeostasis. This study also indicates that FAO
      impairment induced AEC dysfunction is an important contributing factor to the
      pathogenesis of ALI.

PMID- 30183332
TI  - Basal-like Cells in the BAL Fluid: An Echo of Regenerative Crisis in IPF Lungs.

PMID- 30183333
TI  - Dextran-Based Hydrogel as a New Tool for BALB/c 3T3 Cell Cryopreservation Without
      Dimethyl Sulfoxide.
AB  - INTRODUCTION: Cryopreservation provides an efficient way to preserve cells for a
      broad range of medical applications, including cell therapy. In clinical
      practice, cells are frozen in solutions containing dimethyl sulfoxide (DMSO)
      cryoprotectant agents (CPAs) to reduce their damage during the cooling process.
      In the current cell preservation methods, polysaccharides such as dextran, a
      nonpenetrating CPA, are used. However, the cell viability decreases when the
      solution concentration in polysaccharides increases. MATERIALS AND METHODS: To
      overcome this limitation, we have developed a dextran-based hydrogel (PSH) as a
      new CPA. Three molecular weight PSHs (PSH40, PSH70, and PSH500) were synthesized.
      The physicochemical characteristics of PSHs were studied. Then, their
      biocompatibility properties were studied in vitro in BALB/c 3T3 cells according
      to ISO standard 10993-5/12. Crystallization temperature (Tc), that is, ice
      crystal formation, was determined using the thermocouple method. Finally, PSHs
      were used as CPAs in a slow freezing procedure of BALB/c 3T3 cells with
      Voluven(r) (Fresenius Kabi, Sevres, France), and were compared with the DMSO
      procedure. RESULTS: Our results showed that PSHs were biocompatible and did not
      modify the osmolality of the Voluven cryopreservation solution. PSHs decreased
      the Tc when compared with the DMSO procedure. Furthermore, without adding DMSO,
      PSH500 cryopreserved the viability of BALB/c 3T3 cells, and the result was
      similar to that of the control conditions. CONCLUSION: PSH500 could represent an
      alternative to DMSO. It could be used as a new medical device while avoiding DMSO
      side effects on patients.

PMID- 30183334
TI  - Idiopathic Unilateral Vocal Fold Paralysis in Older Patients: Characteristics in
      the Disease Course and Implication of Computed Tomography for Evaluation of
      Etiology.
AB  - OBJECTIVES: This study aimed to compare the characteristics of idiopathic
      unilateral vocal fold paralysis (IUVFP) in elderly versus younger patients,
      including the diagnostic yield of computed tomography (CT) scans for identifying
      the structural causes of IUVFP. METHODS: We retrospectively analyzed medical
      records of the patients initially diagnosed with IUVFP in a single referral
      tertiary hospital. We compared patients' baseline characteristics, initial
      symptoms, laryngoscopic findings, and prevalence of structural causes on CT scans
      with respect to age (younger, <65 years vs older, ?65 years). RESULTS: One
      hundred forty-two patients were enrolled (90 younger, 52 older). Evident
      structural causes were more frequently found on CT in older patients than younger
      patients (40.4% vs 22.2%, P = .034). Among truly idiopathic cases (70 younger, 31
      older), recovered vocal fold mobility was identified in 48.6% younger and 41.9%
      older patients ( P = .666). There was no statistically significant difference in
      the characteristics between unrecovered and recovered subjects of the older
      patients with true IUVFP (all P > .05). CONCLUSIONS: The CT scans provided
      significantly higher diagnostic yields in older patients than younger patients.
      The degrees of symptoms and complications and likelihood of natural recovery did
      not significantly differ between younger and older patients with IUVFP.

PMID- 30183335
TI  - Habitable Climate Scenarios for Proxima Centauri b with a Dynamic Ocean.
AB  - The nearby exoplanet Proxima Centauri b will be a prime future target for
      characterization, despite questions about its retention of water. Climate models
      with static oceans suggest that Proxima b could harbor a small dayside surface
      ocean despite its weak instellation. We present the first climate simulations of
      Proxima b with a dynamic ocean. We find that an ocean-covered Proxima b could
      have a much broader area of surface liquid water but at much colder temperatures
      than previously suggested, due to ocean heat transport and/or depression of the
      freezing point by salinity. Elevated greenhouse gas concentrations do not
      necessarily produce more open ocean because of dynamical regime transitions
      between a state with an equatorial Rossby-Kelvin wave pattern and a state with a
      day-night circulation. For an evolutionary path leading to a highly saline ocean,
      Proxima b could be an inhabited, mostly open ocean planet with halophilic life. A
      freshwater ocean produces a smaller liquid region than does an Earth salinity
      ocean. An ocean planet in 3:2 spin-orbit resonance has a permanent tropical
      waterbelt for moderate eccentricity. A larger versus smaller area of surface
      liquid water for similar equilibrium temperature may be distinguishable by using
      the amplitude of the thermal phase curve. Simulations of Proxima Centauri b may
      be a model for the habitability of weakly irradiated planets orbiting slightly
      cooler or warmer stars, for example, in the TRAPPIST-1, LHS 1140, GJ 273, and GJ
      3293 systems.

PMID- 30183336
TI  - Childhood Obesity and Firmicutes/Bacteroidetes Ratio in the Gut Microbiota: A
      Systematic Review.
AB  - BACKGROUND: The aim of the present study was to undertake a systematic review
      exploring the relationship between childhood obesity and fecal microorganisms, to
      answer the following question: "Are Firmicutes and Bacteroidetes a significant
      risk indicator/factor for obesity in children?" The main search terms were
      "child" and "obesity" together with "gut microbiota" (PubMed: 2005-2017). The
      minimal requirements for inclusion were the evaluation of gut microbiota
      composition and BMI in children between 0 and 13 years of age. METHODS: Assessed
      articles were carefully classified according to a predetermined criterion, and
      the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)
      were considered. Seven articles were critically appraised and used as a basis for
      conclusions. RESULTS: Three studies showed a positive association between
      Bacteroides fragilis and obesity. In addition, a high value of evidence indicated
      that a decrease in the Bacteroidetes phylum and in Bacteroides/Prevotella groups
      was related to high BMI. For the Firmicutes phylum, one high-quality study
      highlighted that it was positively correlated with weight gain. With regard to
      Firmicutes species, Clostridium leptum, Eubacterium hallii, and Lactobacillus
      spp. indicated adipose tissue storage, while Clostridium difficile and the
      Staphylococcus genus were correlated with low BMI. Despite the fact that only one
      study did not perform real-time polymerase chain reaction to quantify the
      microorganisms, its results corroborated those of the studies that did.
      CONCLUSIONS: Changes in Firmicutes and Bacteroidetes phyla/species levels might
      in fact be significant indicators/factors for childhood obesity. However, given
      the small number of articles appraising these entire phyla and the heterogeneity
      among the species assessed, further well-designed studies are required to improve
      the knowledge.

PMID- 30183337
TI  - Evolved changes in breathing and CO2 sensitivity in deer mice native to high
      altitudes.
AB  - We examined the control of breathing by O2 and CO2 in deer mice native to high
      altitude, to help uncover the physiological specializations used to cope with
      hypoxia in high-altitude environments. Highland deer mice (Peromyscus
      maniculatus) and lowland white-footed mice (P. leucopus) were bred in captivity
      at sea level. The first- and second-generation progeny of each population were
      raised to adulthood and then acclimated to normoxia or hypobaric hypoxia (12 kPa
      O2, simulating hypoxia at ~4300 m) for 6-8 weeks. Ventilatory responses to
      poikilocapnic hypoxia (stepwise reductions in inspired O2) and hypercapnia
      (stepwise increases in inspired CO2) were then compared between groups. Both
      generations of lowlanders appeared to exhibited ventilatory acclimatization to
      hypoxia (VAH), in which hypoxia acclimation enhanced the hypoxic ventilatory
      response and/or made breathing pattern more effective (higher tidal volumes and
      lower breathing frequencies at a given total ventilation). In contrast, hypoxia
      acclimation had no effect on breathing in either generation of highlanders, and
      breathing was generally similar to hypoxia-acclimated lowlanders. Therefore,
      attenuation of VAH may be an evolved feature of highlanders that persists for
      multiple generations in captivity. Hypoxia acclimation increased CO2 sensitivity
      of breathing, but in this case the effect of hypoxia acclimation was similar in
      highlanders and lowlanders. Our results suggest that highland deer mice have
      evolved high rates of alveolar ventilation that are unaltered by exposure to
      chronic hypoxia, but they have preserved ventilatory sensitivity to CO2.

PMID- 30183338
TI  - Acute HIIE elicits similar changes in human skeletal muscle mitochondrial H2O2
      release, respiration and cell signaling as endurance exercise even with less
      work.
AB  - It remains unclear whether high-intensity interval exercise (HIIE) elicits
      distinct molecular responses to traditional endurance exercise relative to the
      total work performed. We aimed to investigate the influence of exercise intensity
      on acute perturbations to skeletal muscle mitochondrial function (respiration and
      reactive oxygen species), metabolic and redox signaling responses. In a
      randomized, repeated measures crossover design, eight recreationally active
      individuals (24 +/- 5 years; VO2peak 48 +/- 11 mL.kg-1.min-1) undertook
      continuous moderate-intensity (CMIE: 30 min, 50% peak power output [PPO]), high
      intensity interval (HIIE: 5x4 min, 75% PPO, work-matched to CMIE), and low-volume
      sprint interval (SIE: 4x30 s) exercise, >=7 days apart. Each session included
      muscle biopsies at baseline, immediately and 3 h post-exercise for high
      resolution mitochondrial respirometry ( JO2) and H2O2 emission ( JH2O2), gene and
      protein expression analysis. Immediately post-exercise and irrespective of
      protocol, JO2 increased during complex I+II leak/state-4 respiration but JH2O2
      decreased (p<0.05). AMP-activated protein kinase (AMPK) and acetyl co-A
      carboxylase (ACC) phosphorylation increased ~1.5 and 2.5-fold respectively, while
      thioredoxin-reductase-1 protein abundance was ~35% lower after CMIE vs. SIE
      (p<0.05). At 3 hours post-exercise, regardless of protocol, JO2 was lower during
      both ADP-stimulated state-3 OXPHOS and uncoupled respiration (p<0.05) but JH2O2
      trended higher (p<0.08); PPARGC1A mRNA increased ~13-fold, and peroxiredoxin-1
      protein decreased ~35%. In conclusion, intermittent exercise performed at high
      intensities has similar dynamic effects on muscle mitochondrial function compared
      with endurance exercise, irrespective of whether total workload is matched. This
      suggests exercise prescription can accommodate individual preferences while
      generating comparable molecular signals known to promote beneficial metabolic
      adaptations.

PMID- 30183339
TI  - Bridging angiogenesis and immune evasion in the hypoxic tumor microenvironment.
AB  - Hypoxia (low O2) is a ubiquitous microenvironmental factor promoting cancer
      progression, metastasis and mortality, owing to the ability of cancer cells to co
      opt physiological angiogenic responses. Notwithstanding, the pathophysiological
      induction of angiogenesis results in an abnormal tumor vasculature, further
      aggravating hypoxia in a feed-forward loop that limits the efficacy of molecular
      targeted therapies. Recent studies suggest that besides their canonical roles,
      angiogenic factors promote a panoply of immunosuppressive effects in the tumor
      microenvironment. Therefore, intratumoral hypoxia emerges as a hitherto
      unrecognized mechanism evolutionarily repurposing angiogenic molecules as
      (patho)physiological immunomodulators. On the other hand, antiangiogenic
      therapies could be aimed at impeding both tumor growth and immunotolerance
      towards cancer cells, a beneficial effect that can be countered if hypoxia
      signaling pathways are left unchecked, leading to therapeutic failure. This
      review summarizes evidence supporting the hypothesis that hypoxia acts as a
      common pathophysiological mechanism of resistance to immunotherapeutic and
      antiangiogenic agents whilst proposing potential strategies to curtail resistance
      and mortality in patient bearing solid malignancies.

PMID- 30183341
TI  - Seeking the common, but unsuspected: Arterial hypertension in Indian
      schoolchildren.

PMID- 30183342
TI  - Coronary artery calcium and carotid artery intima-media thickness for the
      prediction of stroke and benefit from statins.
AB  - BACKGROUND: Current guidelines suggest treatment for many individuals who may
      never develop a stroke. We hypothesized that a combination of coronary artery
      calcification (CAC) and carotid artery intima-media thickness (C IMT) data could
      better individualize risk assessment for ischemic stroke and transient ischemic
      attack events. METHODS: A total of 4720 individuals from the Multi-Ethnic Study
      of Atherosclerosis were evaluated for ischemic stroke and transient ischemic
      attack. Cox proportional hazards models for time to incident ischemic
      stroke/transient ischemic attack were used to examine CAC and CIMT as ischemic
      stroke/transient ischemic attack predictors in addition to traditional risk
      factors. We calculated the 10-year number needed to treat by applying the benefit
      observed in ASCOT-LLA to the observed event rates within CAC and CIMT strata.
      RESULTS: Median follow-up was 13.1 years. Compared with individuals with no CAC
      and with CIMT <= 75th percentile, stroke/transient ischemic attack risk increased
      progressively with each CAC category (0, 1-100, >100) among individuals with CIMT
      > 75th percentile. Among participants eligible for statin therapy based on the
      2013 atherosclerotic cardiovascular disease (ASCVD) guidelines (ASCVD risk of
      >5%), 739/2906 (25%) had no CAC and CIMT <= 75th percentile and an observed
      ischemic stroke/transient ischemic attack rate of 2.49 per 1000 person-years. The
      predicted 10-year number needed to treat was 292 for no CAC and CIMT <= 75th
      percentile and 57 for CAC > 100 and CIMT > 75th percentile. CONCLUSION: The
      combination of CIMT and CAC could serve to further refine risk calculation for
      ischemic stroke/transient ischemic attack prevention and may prioritize those in
      most need of statin therapy to reduce ischemic stroke/transient ischemic attack
      risk.

PMID- 30183343
TI  - In Vitro Evaluation of Antimold Activity of Annatto Natural Dye and Its Effects
      on Microbial, Physicochemical, and Sensory Properties of Bread.
AB  - In vitro antimold activity of annatto natural dye against Aspergillus niger,
      Neurospora sitophila, and Rhizopus stolonifer was evaluated with agar well
      diffusion and agar dilution assays. The effects of adding annatto dye (0, 0.5,
      0.75, and 1%) to bread formulations were then examined. Total microbial and
      fungal counts, moisture, color, radical scavenging activity, and sensory analysis
      of bread were monitored. A. niger was the fungus most sensitive to annatto dye in
      vitro. Increased dye concentrations resulted in significant decreases ( P < 0.05)
      in moisture, total microbial and fungal counts, and L*, a*, and b* values of
      bread. The highest antioxidant activity was achieved in the bread with 1% of
      annatto dye. All bread containing annatto dye had acceptable sensory attributes
      as determined by panelists. The addition of annatto dye resulted in bread with a
      longer shelf life and acceptable sensory qualities.

PMID- 30183344
TI  - Successful management of automatic dysfunctional thoughts in the context of
      negative emotions.
AB  - BACKGROUND AND OBJECTIVES: Cognitive and affective overloads trigger automatic
      dysfunctional thoughts and undermine their voluntary management [ADTs; Beck, A.
      T. (1976). Cognitive therapy and the emotional disorders. New York: Meridian;
      Wegner, D. M. (1994). Ironic processes of mental control. Psychology Review,
      101(1), 34-52]. Taking into account intense negative emotions as triggers for the
      ADTs, we explored whether context (i.e., social context) and emotional experience
      (i.e., emotional intensity) predict the successful management of ADTs. We also
      examine the moderating role of difficulties in emotional regulation strategies.
      METHOD: Thirty-eight participants wrote in a personal online diary of at least 10
      times in 40 weeks. We analyzed the conditions for managing ADTs by means of
      multilevel in stages models. RESULTS: Emotional intensity negatively predicted
      successful management of ADTs. Attempts to control ADTs and work context
      positively predicted successful management of ADTs. The negative relation between
      the emotional intensity and the management of ADTs was stronger as individuals
      were less aware of their own emotions, and was weaker as they had less clear
      representations of their own emotions. Superior access to emotion regulation
      strategies explained a stronger relationship between the work context and the
      successful management of ADTs. CONCLUSIONS: We discuss theoretical and practical
      implications of the results.

PMID- 30183345
TI  - Developing and Piloting Videogames to Increase College and University Students'
      Awareness and Efficacy of the Bystander Role in Incidents of Sexual Violence.
AB  - OBJECTIVE: Researchers at the Prevention Innovations Research Center at the
      University of New Hampshire and the Tiltfactor Laboratory at Dartmouth College
      collaborated with students to create two videogames to teach college students
      bystander intervention skills in situations of sexual and relationship violence
      and stalking. MATERIALS AND METHODS: A key strength of the present study is the
      collaboration with students to educate game development. The research team pooled
      its ideas to create a trivia game and an interactive scenario game that were
      pilot tested on first-year students in a midsized campus of a northeastern
      university. "Each game included subject matter related to sexual assault and
      bystander intervention, as well as general campus information so the main themes
      of the game would not be overt and potentially cause participants to resist
      shifting their attitudes about sexual assault and bystander intervention."
      Participants completed a pretest and posttest at each testing session and were
      invited to complete an online follow-up survey 4 weeks following the session.
      RESULTS: Researchers found that both games had a significant impact on
      participant bystander efficacy and attitude scores. The interactive scenario game
      was especially effective in increasing male attitudes toward bystander
      intervention. The results were most salient for the posttest; however, there was
      also an increase in male attitudes at the 4-week follow-up. CONCLUSION: The
      student input was invaluable to the success of the game prototypes. With their
      help, we concluded that gameplay shows promise as an effective way to introduce
      the concept of bystander intervention and increase bystander attitudes and
      efficacy in situations of sexual and relationship violence and stalking to first
      year college students.

PMID- 30183346
TI  - Prevalence of Toxoplasma gondii DNA in Processed Pork Meat.
AB  - Toxoplasma gondii infection may be attributed to the ingestion of pork meat and
      contaminated water. In southern Brazil, the prevalence of blindness caused by T.
      gondii is the highest in the world. Our purpose is to determine the frequency of
      T. gondii DNA in commercial fresh sausage and cured salami samples from Rio
      Grande do Sul state, south of Brazil. A total of 118 samples (sausage and salami)
      from 8 different producers were collected and DNA was extracted. Real-time
      polymerase chain reaction (qPCR) technique was performed to detect T. gondii DNA
      using B1 marker. The frequency of T. gondii DNA among the total number of samples
      (sausage and salami) was 39% (46/118). Among these, a higher frequency of
      positivity was observed in the sausage samples (47.5%) when compared with the
      salami samples (17%). However, the mean parasite concentration was significantly
      higher in the salami samples. The prevalence of T. gondii DNA in fresh sausage
      and cured salami may indicate that infected pigs may be an important source of
      infections and a public health hazard to be considered.

PMID- 30183347
TI  - Neuroscience of Virtual Reality: From Virtual Exposure to Embodied Medicine.
AB  - Is virtual reality (VR) already a reality in behavioral health? To answer this
      question, a meta-review was conducted to assess the meta-analyses and systematic
      and narrative reviews published in this field in the last twenty-two months.
      Twenty-five different articles demonstrated the clinical potential of this
      technology in both the diagnosis and the treatment of mental health disorders: VR
      compares favorably to existing treatments in anxiety disorders, eating and weight
      disorders, and pain management, with long-term effects that generalize to the
      real world. But why is VR so effective? Here, the following answer is suggested:
      VR shares with the brain the same basic mechanism: embodied simulations.
      According to neuroscience, to regulate and control the body in the world
      effectively, the brain creates an embodied simulation of the body in the world
      used to represent and predict actions, concepts, and emotions. VR works in a
      similar way: the VR experience tries to predict the sensory consequences of an
      individual's movements, providing to him/her the same scene he/she will see in
      the real world. To achieve this, the VR system, like the brain, maintains a model
      (simulation) of the body and the space around it. If the presence in the body is
      the outcome of different embodied simulations, concepts are embodied simulations,
      and VR is an embodied technology, this suggests a new clinical approach discussed
      in this article: the possibility of altering the experience of the body and
      facilitating cognitive modeling/change by designing targeted virtual environments
      able to simulate both the external and the internal world/body.

PMID- 30183348
TI  - Serovar-Specific Polymerase Chain Reaction for Detection of Salmonella enterica
      Serovar Indiana.
AB  - Salmonella enterica serovar Indiana (S. Indiana) is a newly emerging pathogen
      with high levels of drug resistance. It has become one of the most common
      Salmonella serovars in China with a worldwide distribution, posing significant
      public health concerns. Detection of S. Indiana by traditional bacteriological
      methods is time-consuming and laborious, which prevents timely surveillance and
      effective control of the pathogen. In this study, comparative genomics was used
      to identify an A7P63_13850 gene that is uniquely present in S. Indiana, but not
      in other Salmonella serovars or any non-Salmonella bacteria. Then, a polymerase
      chain reaction (PCR) assay targeting this serovar-specific gene was established
      for specific detection of S. Indiana. The detection limit of this method is 10 pg
      per reaction for bacterial genomic DNA, being equivalent to 100 colony-forming
      units (CFU) per reaction. The established PCR amplifies all S. Indiana strains (n
      = 56), but none of other Salmonella serovars (n = 146) and non-Salmonella species
      (n = 14). The assay established in this study was also used to detect clinical
      samples from poultry, showed a positivity of 14.7% (23/156) for S. Indiana, which
      were verified by bacteriological methods. The highly sensitive and serovar
      specific PCR for S. Indiana established in this study is suitable and convenient
      for detection of S. Indiana which aids in surveillance and control of the
      pathogen.

PMID- 30183349
TI  - Analysis of IL17A and IL21 Expression in the Small Intestine of Celiac Disease
      Patients and Correlation with Circulating Thioredoxin Level.
AB  - AIMS: Th17 cells and their related cytokines play an important role in the
      pathogenesis of celiac disease (CD), and thioredoxin (Trx) is an extracellular
      TG2 activity regulator. This study evaluated Trx serum levels and the expression
      levels of IL17A, IL21, and Trx genes in biopsies of treated (gluten-free diet)
      and naive (untreated) CD patients compared with healthy individuals. METHODS:
      Duodenal biopsies were collected from treated CD patients (n = 60), healthy
      controls (n = 60), and eight newly diagnosed celiac patients. IL17A, IL21, and
      Trx gene expression was assessed by quantitative polymerase chain reaction (qPCR)
      and compared with serum Trx levels assessed by enzyme-linked immunosorbent assay
      (ELISA). RESULTS: Expression levels of the IL21 and Trx genes were not
      significantly modulated in the CD group compared to the control group, whereas
      the IL17A gene in CD patients was transcribed at significantly higher levels
      among the CD group. Serum concentrations of Trx were significantly increased in
      treated CD patients compared to the control group. CONCLUSIONS: We observed that
      IL17A gene is more highly expressed in duodenal biopsies of CD patients than
      controls, and that the serum levels of Trx are significantly higher in treated CD
      patients than controls. Therefore, the expression levels of these genes and gene
      products, respectively, could potentially be used as diagnostic biomarkers for CD
      patients, although more studies are needed to unravel the underlying molecular
      mechanisms.

PMID- 30183350
TI  - On-Site Treatment of Snow Avalanche Victims: From Bench to Bedside.
AB  - Strapazzon Giacomo and Hermann Brugger. On-site treatment of snow avalanche
      victims: From bench to bedside. High Alt Med Biol. 00:000-000, 2018.-The number
      of avalanche accidents involving winter recreationists has notably increased in
      recent decades due to the increasing popularity of outdoor winter activities. The
      International Liaison Committee on Cardiopulmonary Resuscitation, the
      International Commission for Mountain Emergency Medicine (ICAR Medcom), and the
      Wilderness Medical Society have recently published evidenced-based
      recommendations for the on-site treatment of snow avalanche victims. Despite
      these recommendations, recent studies found poor knowledge and compliance by both
      healthcare providers and laypersons. The aim of this nonsystematic review is to
      provide an updated overview of avalanche accident epidemiology, to present recent
      advances in snow avalanche pathophysiology, and to discuss recent advancements in
      on-site treatment of snow avalanche victims.

PMID- 30183351
TI  - Multidrug Resistance, Biofilm Formation, and Virulence of Escherichia coli
      Isolates from Commercial Meat and Vegetable Products.
AB  - Escherichia coli is an important food safety and public health concern because of
      its pathogenicity and potential for antimicrobial resistance. E. coli isolates as
      food contaminants and their antimicrobial resistance, biofilm-forming ability,
      and virulence genes were analyzed to identify the potential of E. coli in food as
      a major transmission route for antimicrobial resistance and infectious agents.
      Among the 709 samples of minced meat and fresh vegetable products tested, 18.6%
      were positive for E. coli. One hundred nine (29.2%) out of 383 E. coli isolates
      were resistant to 1 or more of the 25 tested antimicrobials. Among the isolates
      from minced pork, the highest rate of resistance was observed for tetracycline
      (52.8%), followed by ampicillin (41.6%). The highest resistance rates against
      tetracycline were coincident with the high amount of tetracycline sold for
      veterinary use. Because penicillin is the most frequently used antimicrobial in
      humans, with 4.52 defined daily doses per 1000 people per day, the high rate of
      resistance to ampicillin (41.6%) supported the potential risk of E. coli food
      contaminants. However, only 1.3% of the isolates possessed the virulence genes
      commonly involved in foodborne outbreaks of E. coli. Sixty-seven isolates (17.5%)
      were multidrug-resistant (MDR), and the highest MDR was observed against 14
      antimicrobials. Most of the MDR E. coli isolates showed biofilm-forming ability.
      Therefore, these isolates will have additional protection from environmental
      stresses, including antimicrobials. Given the importance of E. coli to food
      safety and public health, our results on the prevalence of antimicrobial
      resistance and virulence factors provide useful information for risk management
      options to protect public health.

PMID- 30183352
TI  - Psychiatric disorders associated with acquired brain pathology.
AB  - Acquired brain pathology can be associated with diverse psychiatric
      manifestations. Three major types of psychiatric disorders potentially found in
      cases of acquired brain pathology are examined: (1) psychosis, (2) mood
      disorders, and (3) personality disorders with special emphasis in so-called
      "acquired psychopathy." Two types of psychotic manifestations are reviewed: (a)
      Schizophrenia-like psychosis; (b) Other delusional disorder, specifically,
      somatoparaphrenia and delusional misidentification syndromes, which include
      reduplicative paramnesias, Capgras syndrome, Fregoli syndrome, and "doubles of
      the self-syndrome." Schizophrenia-like psychosis has been reported as sequelae of
      traumatic brain injury with a prevalence of around 1 to 9%. On the other hand,
      the other delusional disorders are usually associated with right hemisphere or
      bilateral lesions. The significance of mood disorders particularly in cases of
      frontal lobe pathology has been reported, including: depression, bipolar
      disorder, alcohol abuse, panic disorder, and increased risk of suicide are
      frequently observed. Personality disorders are frequent in cases of brain
      pathology, particularly frontal lesions. It is concluded that the analysis of the
      psychiatric changes associated with acquired brain pathology has not only a
      clinical importance but also a fundamental interest, advancing the understanding
      of the neurological bases of major psychiatric conditions.

PMID- 30183353
TI  - WHO-AVLT recognition trial: Initial validation for a new malingering index for
      Spanish-speaking patients.
AB  - Several methods for identifying suboptimal effort on Spanish neuropsychological
      assessment have been established. The purpose of this retrospective study was to
      determine whether recognition data from the WHO-AVLT could be employed for
      determination of malingering in a Spanish-speaking sample. Sixteen subjects in
      litigation, 25 neurological patients, and 14 healthy controls completed
      neuropsychological testing. All subjects completed the Test of Memory Malingering
      (TOMM). Inclusion criteria for neurological patients and controls included
      performance above the standard TOMM cutoff. Subjects in litigation were
      classified as probable malingering, through lower than cutoff performance on the
      TOMM and at least one other performance validity measure. Cut-off scores for
      classification of malingering were determined based on the number of recognition
      hits on the WHO-AVLT. The probable malingering group performed significantly
      worse than both groups on recognition hits. A score <10 was determined to be the
      optimal group cutoff, with 56.25% sensitivity and specificity greater than 92%. A
      combination score of 14 increased sensitivity to 68.75%. These findings provide
      initial validation of a new malingering index, based on the number of hits on the
      WHO-AVLT recognition trial. This index will provide valuable information to
      neuropsychologists conducting forensic or clinical evaluations on Spanish
      speaking individuals.

PMID- 30183354
TI  - Utilizing Whole-Exome Sequencing to Characterize the Phenotypic Variability of
      Sickle Cell Disease.
AB  - BACKGROUND: Sickle cell disease (SCD) is a monogenic disease that has wide
      variety of phenotypes with both and environmental factors contributing to its
      severity. METHODS: We performed whole-exome sequencing (WES) in 22 Saudi SCD
      patients to identify variants that could explain differences in disease
      phenotypes. All variants, except those that were benign and likely benign,
      described in the ClinVar database, were considered in our analysis. Gene-based
      association testing using sequence kernel association optimal unified test (SKAT
      O) with small sample adjustment was performed to evaluate the effect of multiple
      variants in genes on SCD phenotypes. RESULTS: The mean age of participants was 28
      (range, 10-48 years). All patients were homozygous for the sickle cell mutation.
      The Benin haplotype was present in 15 patients and the Arab-Indian haplotype in 7
      patients. One patient who had both SCD and CHARGE association was heterozygous
      for pathogenic mutation p.Arg987Ter in the CHD7 gene. One SCD individual who had
      a stroke was a carrier of the pathogenic variant p.Asp36Tyr in the VKORC1 gene
      which is, associated with warfarin resistance. Two patients with steady
      hemoglobin levels of 7.5 and 7.1 g/dL were carriers of the pathogenic mutation
      p.Gly140Ser in the RPL5 gene that is associated with Diamond-Blackfan anemia.
      None of the patients were transfusion dependent. A heterozygous pathogenic
      mutation in the LDLR gene associated with autosomal dominant familial
      hypercholesterolemia was present in one patient with deep venous thrombosis,
      although their cholesterol level was normal. One individual with stroke was a
      carrier for the p.Arg284Ter variant in the NLRP12 gene, which is associated with
      familial cold autoinflammatory syndrome 2. Another patient with stroke and a
      pulmonary embolism was heterozygous for the p.Pro106Leu variant of the MPL gene,
      which has been associated with thrombocytosis. Coding variants in the GOLGB1,
      ENPP1, and PON1 genes showed no association with stroke in our study. SKAT-O
      analysis did not explain SCD heterogeneity. CONCLUSION: WES provided limited
      information to explain the severity of SCD. Whole genome sequencing, epigenetic
      studies, and assessment of environmental factors might expand our knowledge of
      SCD heterogeneity.

PMID- 30183355
TI  - Neuropsychology as a profession in Italy.
AB  - The purpose of this study was to analyze the characteristics of individuals
      working in the field of neuropsychology in Italy, as part of a larger study
      examining the practice of neuropsychology across various countries. They were
      asked about their background, professional training, current work situation,
      types of assessment, preferred diagnostic procedures, as well as the
      rehabilitation techniques, their targeted populations, teaching responsibilities,
      and research activities. A total of 154 professionals completed an online survey
      from April 28, 2016 through June 30, 2016. The majority of participants were
      women, with a mean age of 42.6 years. Participants reported working for the
      National Health System, in private practice, or in private rehabilitation
      facilities. Overall, they reported being very satisfied with their work. Those
      who identified themselves as neuropsychologists primarily assessed individuals
      with dementia, stroke, movement disorders, and traumatic brain injury. While the
      majority of participants declared no problems with the instruments they used,
      others reported complaints, including but not limited to the financial cost of
      current neuropsychological tests and the lack of psychometric support. The main
      perceived obstacles were the lack of willingness to collaborate among
      professionals, the scarcity of academic training programs, and the lack of
      clinical training opportunities.

PMID- 30183356
TI  - TGFalpha/HinfI Polymorphisms Contribute to Nonsyndromic Cleft Lip and Palate in
      Turkish Patients.
AB  - BACKGROUND: Nonsyndromic cleft lip with/without cleft palate (nsCL +/- P) is one
      of the most common birth defects of complex etiology, occurring in ~1/700 live
      births worldwide. A series of epidemiological studies were conducted to
      investigate the association between a transforming growth factor alpha (TGFalpha)
      polymorphism and nsCL +/- P risk. The aim of this study was to investigate the
      association between the TGFalpha/HinfI polymorphisms and nsCL +/- P in Turkish
      patients. METHODS: One hundred fifty-five Turkish subjects were enrolled: 70 nsCL
      +/- P patients and 85 unrelated control individuals. Genomic DNA was isolated
      from peripheral blood leukocytes, and molecular analysis of gene polymorphisms
      was carried out using polymerase chain reaction and restriction enzyme
      digestions. RESULTS: We found significant difference between the TGFalpha gene
      HinfI allele frequencies of the controls and: 1) the occurrence of nonsyndromic
      cleft lip (p = 0.029,); 2) the occurrence of nonsyndromic cleft lip and palate
      (nsCL + P) cases (p = 0.024; and 3) the occurrence of both nsCL +/- nsCLP cases
      (p = 0.0365). The association between age of parents, gender, maternal exposures,
      socioeconomic status and clefts was assessed in each group separately.
      CONCLUSION: Our study indicates that the TGFalpha HinfI gene polymorphism might
      be associated with nsCL +/- P susceptibility, thus contributing to the occurrence
      of nsCL +/- P in Turkish patients. The relatively small sample size of our study
      is one limitation of our study, and future research with larger specimen sets
      from different ethnicities will be required to validate our findings.

PMID- 30183357
TI  - Association Between C1q, TRAIL, and Tim-1 Gene Polymorphisms and Systemic Lupus
      Erythematosus.
AB  - AIM: The present study was designed to examine the relationship between gene
      polymorphisms of C1q, tumor necrosis factor-related apoptosis-inducing ligand
      (TRAIL), T cell immunoglobulin mucin (Tim-1), and systemic lupus erythematosus
      (SLE). MATERIALS AND METHODS: A total of 245 SLE patients were selected from
      February 2012 to August 2016, along with 245 healthy donors as the control group.
      Genomic DNA was extracted from peripheral blood samples from all subjects
      followed by mutational analyses. Gene polymorphisms of the C1q gene (rs292001,
      rs631090, rs294223 loci); the TRAIL gene (1525A/G, 1588A/G, 1595T/C locus); and
      the Tim-1 gene were detected by sequencing after polymerase chain reaction
      amplification. The concentration of anti-C1q antibody and the protein levels of
      sTRAIL/Tim-1 in serum of all subjects were measured by enzyme-linked
      immunosorbent assay. RESULTS: As for the C1q gene, the frequency of the T allele
      at the rs631090 locus in the study group was lower than that in the controls, and
      the frequency of the C allele was higher in the study group than in the healthy
      donors. The frequency of the G allele at the 1525A/G locus of TRAIL gene in the
      study group was significantly higher than those in the control group. The
      frequency of the G allele at -1454G/A of Tim-1 was dramatically higher in the
      study group than in the control group. Anti-C1q antibody concentrations of
      subjects carrying CC and CT genotype at the rs631090 locus were statistically
      higher than TT genotype carriers. The sTRAIL protein level of the TRAIL 1525A/G
      GG genotype carriers was significantly higher than that of GA and AA genotype
      carriers, as well as CC genotype carriers at 1595T/C site compared with CT/TT
      genotype carriers. GG genotype carriers at -1454G/A had higher Tim-1 expression
      levels than GA/AA genotype carriers. CONCLUSION: The C allele at the rs631090
      locus of C1q, the G allele at 1525A/G site of TRAIL, and the G allele of Tim-1 at
      -1454G/A site are susceptibility variants associated with SLE.

PMID- 30183358
TI  - Predictors of cognitive stability or decline during aging: A longitudinal study
      in primary care.
AB  - We aimed to identify the early predictors of cognitive decline, and primary care
      physicians' (PCP) ability to diagnose cognitively impaired subjects, in a cohort
      of individuals recruited in primary care centers. Independent adults, aged >=50
      years at inception, with an overall low level of education, undertook a
      prospective clinical and cognitive evaluation targeting memory, attention and
      executive functions. At follow-up subjects were classified as cognitively normal
      (CN) or impaired (CI). Of 275 subjects (70.4 +/- 8.3 years old, 176 females, 7.5
      +/- 4.4 education, 162 with MRI), 31 (11.2%) presented CI 4.9 years later, the
      majority (64.5%) presenting subjective cognitive complaints. PCP could correctly
      identify 40% of CI individuals, particularly if they presented current cognitive
      complaints. Male sex (OR = 3.117; CI95%: 1.007-9.645), age (OR = 1.063; CI95%:
      1.004-1.126) and baseline scores on TMT-B (OR = 0.225; CI95%: 0.073-0.688) and
      Vocabulary (OR =  0.940; 95% CI: 0.894-0.986) predicted CI. This study shows that
      measures indicating poor cognitive reserve and low executive performance (as
      shown by low vocabulary and executive test scores, respectively) can be early
      indicators of the risk of decline, stressing the role of cognitive assessment as
      part of prevention/early intervention programs. The results also underline the
      need to help PCP to improve the detection of subjects with cognitive decline.

PMID- 30183359
TI  - An Examination of Triarchic Psychopathy Constructs in Female Offenders.
AB  - This study sought to expand scientific knowledge on psychopathic personality
      traits in female offenders by evaluating the relationship between MMPI-2-RF
      triarchic scales and self-reported external variables in a sample of 205 female
      offenders. Results indicated that boldness was inversely related to internalizing
      dysfunction, including suicidal behavior, psychosis, youth conduct problems,
      problems stemming from alcohol use, and a history of outpatient mental health
      treatment. Meanness was positively related to internalizing dysfunction as well
      as youth conduct problems, anger, prison disciplinary reports, and psychosis.
      Disinhibition was associated with a history of abuse in childhood, suicidal
      behavior, internalizing dysfunction, problems associated with alcohol and drug
      use, family history of mental illness, prison disciplinary reports for violence,
      number of previous criminal charges, and anger. Consistent with views of
      psychopathy as a configural condition, interactive effects of boldness with
      disinhibition and meanness were observed for multiple key external variables
      (e.g., conduct problems, substance use, nonsuicidal self-injurious behavior).
      This study provides further evidence for the triarchic conceptualization of
      psychopathy in female offenders and lends additional support for the validity of
      MMPI-2-RF triarchic psychopathy scales.

PMID- 30183360
TI  - Preliminary study of spatial cognition relating to nonimpact mTBI.
AB  - Sweeney and Johnson found that individuals that sustained mild traumatic brain
      injury without impact to the head (Nonimpact) demonstrated significantly slower
      performance than participants that suffered mild traumatic brain injury with
      impact to the head and normal controls on the Tactile Form Recognition Test
      (TFR). The current study explored the spatial cognition of three groups of
      Nonimpact participants classified as Deficient, Perfectly Normal, and Normal on
      the basis of TFR response time. Dependent variables consisted of
      neuropsychological tests requiring tactile- and/or visual-spatial perception and
      memory. Univariate analysis of variance (ANOVAs) were carried out, with false
      positive findings controlled by adjusting p-values using the False Detection
      Rate. Deficient TFR individuals performed at significantly inefficient levels
      relative to both Perfectly Normal and Normal TFR patients on tactile-spatial
      tests requiring the perception and recognition of multiple geometric
      configurations with the left hand, tactile-spatial memory for these shapes, and
      identification of numbers traced on the fingertips of the right hand. TFR
      Deficiency appeared to negatively affect performance on visual-spatial tests
      involving memory for abstract concepts and rapid association of numbers and
      geometric shapes, but only in relation to Perfectly Normal participants.

PMID- 30183361
TI  - Comparing two models of performance validity assessment in patients with
      Parkinson's disease who are candidates for deep brain stimulation surgery.
AB  - Utility of standalone and embedded performance validity tests (PVTs) as well as
      the decision-making algorithms used to reach clinical conclusions about credible
      and noncredible performance can be population specific. To better understand PVT
      utility in Parkinson's disease candidates for deep brain stimulation (DBS) we
      present on two aims: 1) establishing the frequency data of below-criterion
      responding for the Medical Symptom Validity Test and three embedded PVTs in a
      sample of 47 patients with Parkinson's disease, and 2) comparing the efficacy of
      two models for clinical-decision making regarding noncredible performance.
      Consistent with expectations from previous studies and desired specificity
      values, our retrospective analysis indicated that in this sample of presumably
      well-motived patients, the rate of below-criterion responding was less than 10%
      for all PVTs administered. Regarding our model comparison, we compared a typical
      PVT battery that required administration of a standalone measure in all cases
      against a recently proposed low risk algorithm that attempts to lower testing
      burden by relying more heavily on embedded PVTs with administration of a
      standalone measure only in the event of below-criterion performance on an
      embedded indicator. Results suggest that for patients with Parkinson's disease
      judged to be at limited risk for noncredible performance, a low risk PVT model
      may prove both more efficient and less prone to error than a more typical model.
      Implications for clinical decision-making are discussed, as are limitations of
      the study and its generalizability.

PMID- 30183362
TI  - Psychological disturbance and cognitive functioning in TBI patients.
AB  - The current study examined psychopathology and neuropsychological test
      performance in a traumatic brain injury (TBI) patient sample. Previous research
      has found that the Minnesota Multiphasic Personality Inventory - Second Edition
      (MMPI-2) indices of psychological disturbance were related to specific
      neuropsychological tests of attention and memory. Furthermore, higher scores on
      clinical scale 2 (Depression) and higher scores on the content scales of Fears
      and Bizarre Mentation of the MMPI-2 were related to poorer performance in, most
      notably, Attention and List Learning factors. The present study sought to extend
      the research by adding a neuropsychological measure of conceptual reasoning. A
      sample of 116 TBI patients referred for evaluation at a private practice clinic
      were administered a battery of neuropsychological measures of list learning,
      working memory, verbal memory, visuographic memory, and conceptual reasoning, as
      well as the MMPI-2 to assess emotional functioning. Regression analysis indicated
      that an overall model of MMPI-2 indices significantly predicted poorer
      performance on List Learning. More specifically, higher scores on the content
      scales of Obsessions and Fears were most robustly associated with poorer
      neuropsychological test performance for List Learning and Working Memory
      respectively. Findings suggest psychopathology is correlated with performance on
      neuropsychological measures for TBI patients.

PMID- 30183363
TI  - Confirmatory factor analysis of a myalgic encephalomyelitis and chronic fatigue
      syndrome stigma scale.
AB  - This study adapted a chronic illness stigma scale and explored its psychometric
      properties. The main purposes were to confirm the factor structure of the
      instrument with this population and address the previous factor intercorrelation
      discrepancies. Five hundred and fifty-four individuals with myalgic
      encephalomyelitis or chronic fatigue syndrome completed the adapted stigma scale.
      Results document the stigma experienced by an international sample of individuals
      with myalgic encephalomyelitis and chronic fatigue syndrome. Factors demonstrated
      good internal consistency, and a model fit was found in a confirmatory factor
      analysis. Participants endorsed high levels of stigma, estrangement, and
      disclosure. Implications of these findings and future directions are discussed.

PMID- 30183364
TI  - Investigating the Modifications of Sugar Perception and Consumption in Cancer
      Patients.
AB  - The idea that sugar feeds the tumor cells is relayed by some health professionals
      and media alike. Patients may be torn between what they read in the media and
      their food preferences during and after treatment. With this survey, we aim at
      understanding the perception and overall consumption patterns of sugar in cancer
      patients together with possible physiological and psychological triggers. We
      decided not to include quantitative nutritional measures of the sugar
      consumption. The survey was distributed in a hospital setting and through a
      cancer support online network. Results have shown that opinion on sugar was
      globally "average". However, there were differences depending on sex and age.
      Half of the patients declared having a decreased consumption of sugar and sweet
      products while 26% declared an increased consumption. When looking at
      psychological triggers to consumption, the weight of fatigue and worry increased
      after cancer diagnosis compared to before. Environmental triggers such as mixed
      messages from health professionals or the media need to be further investigated.
      In line with ESPEN guidelines, we advise to maintain moderate sugar intake as
      part of a healthy diet to prevent malnutrition as a first line of defense against
      cancer-associated morbidity and mortality.

PMID- 30183365
TI  - Treatment Recommendations in Oncology Visits: Implications for Patient Agency and
      Physician Authority.
AB  - Although oncology is a major site for clinician-patient treatment negotiation
      requiring a careful balance of potentially competing viewpoints, little is known
      about how clinicians promote their treatment recommendations to patients and what
      the manner of promotion tells us about the oncologist-patient relationship.
      Utilizing an already-established schema of coding treatment recommendations, I
      draw on 61 treatment recommendations to examine treatment decision-making in
      oncology. This paper investigates how physicians balance asserting their
      authority while at the same time attending to patient agency and involvement in
      decision-making. Taking this one step further, this paper explores how physicians
      negotiate decision-making with patients given that they occupy a liminal state
      between obligations to policy imperatives and commitments to their professional
      knowledge and technical expertise. How do they do this, and what accounts for
      this? To answer these questions, this paper analyzes the ways in which physicians
      present treatment recommendations and the treatment contexts in which they are
      made.

PMID- 30183366
TI  - The Development and Validation of the Autotelic Personality Questionnaire.
AB  - Autotelic personality is a constellation of dispositional attributes that
      facilitate engagement and enjoyment in daily activities. However, there is no
      existing measurement directly capturing the attributes of autotelic personality
      that are identified in the literature. In the three studies reported here (total
      N = 900), we developed an Autotelic Personality Questionnaire (APQ) and evaluated
      its reliability and validity. Results from the studies provide support for
      adequate internal consistency, longitudinal invariance, and test-retest
      reliability (Study 1 and Study 2). Furthermore, APQ scores were significantly
      correlated with measures of conscientiousness, openness to experience,
      extraversion, neuroticism, and internal locus of control. In addition, APQ scores
      predicted flow proneness and satisfaction with life (Study 2). These results
      provide support for construct and criterion validity. Finally, people high in
      autotelic personality experienced more flow state than those low in autotelic
      personality during a word unscrambling task (Study 3), indicating good criterion
      validity of the APQ scores. Limitations, future research, and implications are
      discussed.

PMID- 30183367
TI  - The Vulvar Vernacular: Dilemmas Experienced and Strategies Recommended by Women
      with Chronic Genital Pain.
AB  - This manuscript uses Goldsmith's (2004) normative model of social support to
      explore conversations women have with a romantic partner about vulvodynia. Twenty
      six women with vulvodynia participated in semi-structured interviews in which
      they described conversational goals, discussed challenges, and offered advice to
      others managing vulvodynia. As this study was concerned with interactions with
      romantic partners both present and past, women with vulvodynia, not their
      partners, were the targets of recruiting efforts. Two key communicative dilemmas
      emerged from the data analysis: (a) I need to talk to you, but I can't, and (b) I
      want to be honest, but not too honest. These dilemmas represent ambiguity about
      the causes and duration of pain and the implications that being unable to have
      pain-free intercourse has for their relationships and identities as women. Three
      strategies, communicative practices for managing dilemmas, also emerged: (a)
      reframe the illness, (b) refocus the relationship, and (c) redefine intimacy. The
      theoretical and practical implications of this research are socially situated
      within timely conversation about women, their bodies, and their roles.

PMID- 30183368
TI  - Neurobehavioral symptom validity and performance validity in veterans: Evidence
      for distinct outcomes across data types.
AB  - Self-reported traumatic brain injury (TBI) is common in combat veterans, and
      identification of psychiatric and neuropsychological consequences following TBI
      has become a priority for veteran healthcare. Given the importance of accurately
      capturing symptoms potentially related to TBI in VA settings, validity metrics
      are frequently used to evaluate both neuropsychological testing validity and the
      validity of symptom self-reports. The Validity-10 of the Neurobehavioral Symptom
      Inventory is one such metric that was designed to evaluate symptom over-reporting
      and thus identify individuals who may produce inconclusive testing profiles.
      However, the Validity-10's ability to predict objective effort during
      neuropsychological testing has not been sufficiently explored in veterans.
      Clinical evaluation data were collected from 295 veterans seeking treatment in a
      VA TBI clinic. We examined whether the Validity-10 can predict invalid
      performance on a battery of neuropsychological tests. Validity-10 was a poor
      predictor of performance validity metrics. Results provide a conceptual
      replication of earlier work demonstrating that performance and symptom validity
      are divergent. As such, separate evaluation of these domains is warranted during
      evaluations conducted in veteran TBI populations.

PMID- 30183369
TI  - Emerging evidence for speeded alphabet printing as a measure of processing speed
      and working memory.
AB  - Alphabet Printing (in the forward and backward order) is a brief and highly
      portable test with promise as a screening measure of processing speed and simple
      working memory, constructs which are only minimally assessed in many of the most
      commonly-used cognitive screening instruments. The aim of this project was to
      examine the construct validity of timed Alphabet Printing in a sample of 254
      Veterans with cognitive complaints and a history of possible head injury.
      Criterion measures included more established tests of processing speed and simple
      working memory, including the Trail Making Test and the Digit Span subtest from
      the fourth edition of the Wechsler Adult Intelligence Scales. Alphabet Printing
      scores moderately correlated with the criterion measures of attention, working
      memory, and processing speed, and demonstrated acceptable classification accuracy
      in discriminating between individuals with and without evidence of cognitive
      impairment on Trails B. These findings provide additional support for the
      possible utility of including Alphabet Printing during cognitive screenings or as
      part of a larger neuropsychological test battery.

PMID- 30183370
TI  - Probiotics (Lactobacillus acidophilus and Lactobacillus rhamnosus GG) in
      Conjunction with Celecoxib (selective COX-2 inhibitor) Modulated DMH-Induced
      Early Experimental Colon Carcinogenesis.
AB  - Epidemiological and experimental observations have shown that nonsteroidal anti
      inflammatory drugs especially selective cyclooxygenase-2 (COX-2) inhibitors and
      probiotics reduce the incidence risk of colon cancer. Therefore, the present
      study was designed to assess the prophylactic potentials of probiotics
      (Lactobacillus acidophilus and Lactobacillus rhamnosus GG) in conjunction with
      celecoxib, a selective cox-2 inhibitor in 1,2 dimethylhydrazine dihydrochloride
      (DMH)-induced experimental colon carcinogenesis, a well-established, well
      appreciated and widely used model for colorectal cancer that shares many
      similarities to human sporadic colorectal cancer with respect to response to some
      promotional and preventive agents. More specifically, it was observed that L.
      rhamnosus GG + celecoxib + DMH-treated animals had significantly reduced aberrant
      crypt foci (ACF) count and the expression of procarcinogenic molecular markers
      (beta-catenin, NF-kappaB, and COX-2) in early experimental colon carcinogenesis
      compared with probiotic-DMH, celecoxib-DMH or DMH-treated animals. This is the
      first ever such study to demonstrate that probiotic in conjunction with celecoxib
      can be opted as an alternate prophylactic strategy in highly susceptible
      individuals to reduce both the incidence and severity of the life style diseases
      as prevention is better than cure.

PMID- 30183371
TI  - Self-awareness deficits associated with lower treatment motivation in cocaine
      addiction.
AB  - BACKGROUND: Individuals with cocaine use disorder (CUD) often display behaviours
      that are paradoxically misaligned with their situation. Typical examples include
      poor treatment motivation and inconsistent self-reported craving. These
      behaviours may reflect impairments in the awareness of one's own behaviour.
      OBJECTIVES: We examined whether impaired self-awareness of addiction-related
      frontostriatal dysfunction (i.e., symptoms of apathy, disinhibition, and
      executive dysfunction) was associated with treatment motivation and craving.
      METHODS: Sixty-five outpatients with CUD (57 male) and their informants (those
      who knew the patient well) completed parallel self and informant versions of the
      Frontal Systems Behaviour Scale. Self-awareness was indexed through the
      discrepancy between self and informant scores in the three sub-scales; apathy,
      disinhibition and executive dysfunction. The University Rhode Island Change
      Assessment Scale assessed treatment motivation. Self-reported craving was
      assessed using a visual analogue scale. Multiple linear regression models
      examined associations between self-awareness and treatment motivation and
      craving, adjusting for sociodemographic factors and lifetime drug use. RESULTS:
      We found an inverse relationship between self-awareness of symptoms of
      disinhibition and treatment motivation maintenance. Although impaired awareness
      of disinhibition was also correlated with craving, this association was not
      significant after adjusting for sociodemographic factors and drug use. The apathy
      and executive dysfunction awareness scores were not associated with treatment
      motivation or craving. CONCLUSION: We show that people with lower insight into
      their disinhibition problems (e.g., impulsivity, mood instability) have more
      problems maintaining motivation when initiating treatment. Findings suggest that
      self-awareness interventions could be useful to prevent premature treatment
      dropout and improve addiction treatment outcomes.

PMID- 30183372
TI  - Reliability and validity of a motion-based reaction time assessment using a
      mobile device.
AB  - Information processing speed is often altered following a concussion. Few
      portable assessments exist to evaluate simple reaction time (SRT) in hospitals
      and clinics. We evaluated the use of a SRT application for mobile device
      measurement. 27 healthy adults (age = 30.7 +/- 11.5 years) completed SRT tests
      using a mobile device with Sway, an application for SRT testing. Participants
      completed computerized SRT tests using the Computerized Test of Information
      Processing (CTIP). Test-retest reliability was assessed using intraclass
      correlation coefficients (ICC) between Sway trials. Pearson correlations and
      Bland-Altman analyses were used to assess criterion validity between Sway and
      CTIP means. ICC comparisons between Sway tests were all statistically
      significant. ICCs ranged from 0.84-0.90, with p-values <.001. A one-way analysis
      of variance (ANOVA) revealed no significant differences between trials (F3,104 = 
      1.35, p = .26. Pearson correlation between Sway and CTIP outcomes yielded a
      significant correlation (r = 0.59, p = .001). The mean difference between
      measurement methods was 43.7 ms, with limits of agreement between -140.8-53.4 ms.
      High ICC indicates Sway is a reliable method to assess SRT. A strong correlation
      and clinically acceptable agreement between Sway and the computer-based test
      indicates that Sway is suited for rapid administration of SRT testing in healthy
      individuals. Future research using Sway to assess altered information processing
      in a population of individuals after concussion is warranted.

PMID- 30183373
TI  - Plasma glycomics predict cardiovascular disease in patients with ART-controlled
      HIV infections.
AB  - Despite effective control of HIV infection with antiretroviral drugs, individuals
      with HIV have high incidences of secondary diseases. These sequelae, such as
      cardiovascular disease (CVD), are poorly understood and represent a major health
      burden. To date, predictive biomarkers of HIV-associated secondary disease have
      been elusive, making preventative clinical management essentially impossible.
      Here, we applied a newly developed and easy to deploy, multitarget, and high
      throughput glycomic analysis to banked HIV+ human plasma samples to determine
      whether the glycome may include biomarkers that predict future HIV-associated
      cardiovascular events or CVD diagnoses. Using 324 patient samples, we identified
      a glycomic fingerprint that was predictive of future CVD events but independent
      of CD4 counts, diabetes, age, and birth sex, suggesting that the plasma glycome
      may serve as a biomarker for specific HIV-associated sequelae. Our findings
      constitute the discovery of novel glycan biomarkers that could classify patients
      with HIV with elevated risk for CVD and reveal the untapped prognostic potential
      of the plasma glycome in human disease.-Oswald, D. M., Sim, E. S., Baker, C.,
      Farhan, O., Debanne, S. M., Morris, N. J., Rodriguez, B. G., Jones, M. B., Cobb,
      B. A. Plasma glycomics predict cardiovascular disease in patients with ART
      controlled HIV infections.

PMID- 30183374
TI  - Brain microvascular endothelial cell exosome-mediated S100A16 up-regulation
      confers small-cell lung cancer cell survival in brain.
AB  - Small cell lung cancer (SCLC) is the most aggressive histologic subtype of lung
      cancer, with a strong predilection for early brain metastases. Despite efforts
      and advances in new therapeutics for SCLC, the prognosis of patients with SCLC
      with brain metastases is consistently poor. Therefore, a better understanding of
      the mechanisms of SCLC brain metastasis is important in improving current
      treatments. In this study, elevated S100A16 levels were associated with SCLC
      brain metastases, which was a possible secondary event arising from the brain
      metastatic microenvironment. Using an in vitro cell coculture system, we found
      that the coculturing of SCLC cells with human brain microvascular endothelial
      cells (HBMECs) led to an increased expression of S100A16 in SCLC cells.
      Conversely, treatment of HBMECs with GW4869, an inhibitor of exosome release,
      significantly blocked this effect in the cocultured SCLC cells. Alternatively,
      the results from Western blot analyses and immunofluorescence indicated that the
      HBMEC exosomes purified by ultracentrifugation also induced the elevation and
      translocation from the cytoplasm to the nucleus of S100A16 in the recipient SCLC
      cells. The inhibition experiments demonstrated that elevated S100A16 contributed
      a benefit of HBMEC exosomes for the survival of the recipient SCLC cells under
      stress. Moreover, the elevation of S100A16 in SCLC cells prevented the loss of
      mitochondrial membrane potential (Deltapsim) and enhanced resistance to apoptosis
      under stressful conditions, which were determined by Annexin V/propidium iodide
      and JC-1 assay. Further results showed that the S100A16-mediated protective
      effect was caused by the presence of an important element in Deltapsim,
      prohibitin (PHB)-1, a protein in the mitochondrial inner membrane. Conversely,
      the delivery of PHB-1 siRNAs into S100A16 overexpressing SCLC cells weakened
      these protective effects. Our findings suggest that elevated S100A16 plays an
      active role in facilitating the survival of SCLC cells through modulating the
      mitochondrial function, identifying S100A16 as an important potential target in
      SCLC brain metastasis.-Xu, Z.-H., Miao, Z.-W., Jiang, Q.-Z., Gan, D.-X., Wei, X.
      G., Xue, X.-Z., Li, J.-Q., Zheng, F., Qin, X.-X., Fang, W.-G., Chen, Y.-H., Li.
      B. Brain microvascular endothelial cell exosome-mediated S100A16 up-regulation
      confers small cell lung cancer cell survival in brain.

PMID- 30183375
TI  - Phosphorylation of E-box binding USF-1 by PI3K/AKT enhances its transcriptional
      activation of the WBP2 oncogene in breast cancer cells.
AB  - WW domain binding protein 2 (WBP2), a transcriptional coactivator, plays a vital
      role in breast tumorigenesis. It positively regulates estrogen receptor, Hippo,
      and Wnt pathways, which subsequently enhance the transcription of downstream
      target genes contributing to cancer. Understanding the regulation of the
      expression and activity of WBP2 oncoprotein has implication in cancer therapy. We
      have previously reported that WBP2 is regulated at the post-translational and
      post-transcriptional levels. However, its regulation at the transcriptional level
      is not known. In this study, the minimal promoter region of WBP2 that is critical
      for its transcription was identified. The E-box motif in the WBP2 promoter was
      demonstrated to be essential for its transcription. The E-box binding protein
      upstream stimulatory factor 1 (USF-1) was discovered to be a key transcription
      factor for WBP2 by yeast one-hybrid analysis and was validated through reporter
      and chromatin immunoprecipitation assays and tandem mass spectrometry, which also
      suggested that USF-1 acts by regulating a network of genes, in addition to WBP2,
      associated with cell movement, proliferation, cell-cycle, and survival cellular
      processes. USF-1 is overexpressed in majority of the breast cancer cell lines and
      tissues tested, and has profound effects on cancer cell proliferation. USF-1
      mediated transcription of WBP2 was demonstrated to be inducible by insulin, which
      led to AKT-mediated phosphorylation of USF-1 that modulated its ability to bind
      to the WBP2 promoter and activate its transcription. This study sheds new light
      onto the regulation of the WBP2 oncogene at the transcriptional level by a novel
      oncogenic transcription factor, USF-1. USF-1 is a potential drug target for
      treatment of WBP2-positive breast cancer.-Ramos, A., Miow, Q. H., Liang, X., Lin,
      Q. S., Putti, T. C., Lim, Y. P. Phosphorylation of E-box binding USF-1 by
      PI3K/AKT enhances its transcriptional activation of the WBP2 oncogene in breast
      cancer cells.

PMID- 30183376
TI  - Gut microbiome catabolites as novel modulators of muscle cell glucose metabolism.
AB  - The gut microbiome supplies essential metabolites such as short-chain fatty acids
      to skeletal muscle mitochondria, and the composition and activity of the
      microbiota is in turn affected by muscle fitness. To further our understanding of
      the complex interactions between the gut microbiome and muscle, we examined the
      effect of microbiota-derived phenolic metabolites on the ability of human muscle
      cells to take up and metabolize glucose. As a model, we used the differentiated
      human skeletal muscle myoblast line, LHCN-M2, which expresses typical muscle
      phenotypic markers. We initially tested a selected panel of parent phenolic
      compounds and microbial metabolites, and their respective phenolic conjugates, as
      found in blood. Several of the tested compounds increased glucose uptake and
      metabolism, notably in high glucose- and insulin-treated myotubes. One of the
      most effective was isovanillic acid 3 -O-sulfate (IVAS), a metabolite from the
      microbiome found in the blood, primarily derived from consumed cyanidin 3 -O
      glucoside, a major compound in berry fruits. IVAS stimulated a dose-dependent
      increase in glucose transport through glucose transporter GLUT4- and PI3K
      dependent mechanisms. IVAS also up-regulated GLUT1, GLUT4, and PI3K p85alpha
      protein, and increased phosphorylation of Akt. The stimulation of glucose uptake
      and metabolism by a unique microbiome metabolite provides a novel link among
      diet, gut microbiota, and skeletal muscle energy source utilization.-Houghton, M.
      J., Kerimi, A., Mouly, V., Tumova, S., Williamson, G. Gut microbiome catabolites
      as novel modulators of muscle cell glucose metabolism.

PMID- 30183377
TI  - MicroRNA-493 targets STMN-1 and promotes hypoxia-induced epithelial cell cycle
      arrest in G2/M and renal fibrosis.
AB  - Hypoxia plays an important role in the development of renal fibrosis. G2/M arrest
      in renal tubular cells is an important pathway in the development of chronic
      kidney disease. It is unknown whether hypoxia leads to renal fibrosis via the
      regulation of G2/M arrest in renal tubular epithelial cells. For the first time,
      to our knowledge, we showed that hypoxia induces G2/M arrest in renal tubular
      cells leading to renal fibrosis, and microRNA are involved in this regulation. We
      compared microRNA expression between hypoxia and normoxia in HK2 cells and found
      miR-493 to be highly expressed at 24 and 48 h after hypoxia. The overexpression
      of miR-493 reduced the expression of the cell cycle regulator, Stathmin (STMN)-1,
      and increased the percentage of G2/M phase cells and profibrotic factors in HK2
      cells. Targeting STMN-1 with short hairpin RNA produced an effect similar to that
      of miR-493 overexpression. On contrast, the miR-493 inhibitor reversed these
      effects in vitro. Consistent with these results, miR-493 sponge adeno-associated
      virus reduced the expression of profibrotic factors and increased STMN-1 in vivo.
      In summary, these results suggest that the miR-493-STMN-1 pathway contributes to
      hypoxia-induced tubular epithelial cell G2/M arrest and renal fibrosis.
      Abrogating G2/M arrest and blocking the miR-493-STMN-1 pathway will provide
      further insight for the development of antifibrosis therapy.-Liu, T., Liu, L.,
      Liu, M., Du, R., Dang, Y., Bai, M., Zhang, L., Ma, F., Yang, X., Ning, X., Sun,
      S. microRNA-493 targets STMN-1 and promotes hypoxia-induced epithelial cell cycle
      arrest In G2/M and renal fibrosis.

PMID- 30183378
TI  - Cysteinyl leukotriene receptor 1 (cysLT1R) regulates osteoclast differentiation
      and bone resorption.
AB  - Excessive bone resorption induced by abnormal osteoclast differentiation has been
      associated with bone microstructure damage and bone-associated disorders,
      including osteoporosis. Here, we investigated the physiological roles of the type
      1 cysteinyl leukotriene receptor (cysLTR-1) and the pharmacological functions of
      the specific cysLTR-1 antagonist montelukast on M-CSF- and RANKL-induced
      osteoclast differentiation. We showed that cysLTR-1 but not cysLTR-2 is expressed
      in osteoclast precursor cells: mouse bone marrow-derived macrophages (BMMs). We
      also found that treatment with M-CSF and RANKL significantly increased expression
      of cysLTR-1. Overexpression of cysLTR-1 promoted osteoclast differentiation of
      BMMs by increasing NFATc1 and TRAP. In contrast, treatment with montelukast
      prevented M-CSF- and RANKL-induced osteoclast differentiation of BMMs.
      Mechanically, our findings demonstrate that montelukast treatment attenuated
      activation of the ERK1/2, p38, JNK and NF-kappaB signalling pathways.
      Additionally, we reported that montelukast treatment ameliorated the generation
      of ROS and calcium signalling. Importantly, the co-immunoprecipitation assay
      displayed that montelukast treatment prevented the interaction of RANK and TRAF6.
      Finally, in vivo experiments indicated that montelukast rescued the reduction of
      bone volume as well as trabecular number in an ovariectomy mouse model.

PMID- 30183379
TI  - pH-sensitive and biocompatible quercetin-loaded GO-PEA-HA carrier improved
      antitumour efficiency and specificity.
AB  - A novel drug carrier was designed based on a new biomaterial, that is, graphene
      oxide (GO), to improve the efficiency and specificity of anticancer drug. In this
      study, GO was successively modified with polyetheramine (PEA) and hyaluronic acid
      (HA). The carrier was utilized to load an antitumor component, that is, quercetin
      (Que), which was derived from traditional Chinese medicine, namely the pagoda
      tree flower bud. This drug delivery system (DDS) exhibited pH sensibility under
      subacid condition and good biocompatibility even when GO concentration reached
      350 MUg/mL. Moreover, the antitumor efficacy was doubly improved and more long
      acting compared with Que alone. Results show that the GO-based material has
      potential clinical applications for antitumor drug delivery.

PMID- 30183380
TI  - Improved oral bioavailability of magnolol by using a binary mixed micelle system.
AB  - The aim of this study was to prepare two novel magnolol (MO)-loaded binary mixed
      micelles (MO-M) using biocompatible copolymers of Soluplus (SOL) and Solutol(r)
      HS15 (HS15), SOL and d-alpha-tocopheryl polyethylene glycol 1000 succinate
      (TPGS), to improve magnolol's poor solubility and its oral bioavailability. The
      organic solvent evaporation method was used to obtain two MO-M by optimization;
      one was prepared by using SOL and HS15 (MO-H), and the other was prepared by
      using SOL and TPGS (MO-T). The entrapment efficiency (EE%) and drug loading (DL%)
      of MO-T were 94.61 +/- 0.91% and 4.03 +/- 0.19%, respectively, and the MO-H has
      higher EE% and DL% (98.37 +/- 1.23%, 4.12 +/- 0.16%). TEM results showed that the
      morphology of MO-M was homogeneous and was spherical in shape. The dilution
      stability of MO-M did not undergo significant changes. Permeability of MO-M
      across a Caco-2 cell monolayer was enhanced in Caco-2 cell transport models. The
      pharmacokinetics study showed that the relative oral bioavailability of MO-T and
      MO-H increased by 2.39- and 2.98-fold, respectively, compared to that of raw MO.
      This indicated that MO-H and MO-T could promote absorption of MO in the
      gastrointestinal tract. Collectively, the mixed micelles demonstrated greater
      efficacy as a drug delivery system. The development of these novel mixed micelles
      is valuable for resolving the poor solubility and bioavailability of drugs.

PMID- 30183381
TI  - Saccadic impairment in chronic traumatic brain injury: examining the influence of
      cognitive load and injury severity.
AB  - OBJECTIVE: Previous research suggests that saccadic eye movements can be uniquely
      sensitive to impairment in chronic traumatic brain injury (TBI). This study was
      conducted to examine saccadic eye movements across varying levels of cognitive
      load and TBI history/severity. We hypothesized that saccadic impairment in
      chronic mild and moderate-severe TBI would be most pronounced under conditions of
      high cognitive load. METHODS: In total, 61 participants (including n = 20 with
      chronic mild TBI, n = 15 with chronic moderate-severe TBI, and 26 uninjured
      controls) completed a battery of conventional neuropsychological tests and the
      Fusion n-Back Test, which measures manual and saccadic response time (RT) across
      varying cognitive load and cueing conditions. RESULTS: Consistent with our
      hypotheses, chronic mild and moderate-severe TBI were associated with substantial
      saccadic impairment under conditions of high cognitive load. Participants with
      moderate-severe TBI also demonstrated saccadic impairment at low levels of
      cognitive load. TBI groups and uninjured controls did not differ significantly on
      manual metrics or conventional neuropsychological measures. CONCLUSIONS: This
      study provides additional support for the value of eye tracking for enhanced
      assessment of TBI. Additionally, findings suggest that TBI is associated with
      greatest susceptibility to oculomotor interference under high levels of cognitive
      load.

PMID- 30183382
TI  - Functional graphene oxide as cancer-targeted drug delivery system to selectively
      induce oesophageal cancer cell apoptosis.
AB  - Graphene oxides (GO) is a promising building material to fabricate desired drug
      delivery system due to its excellent physicochemical properties. In this study,
      an innovative nano-drug (Ori@GE11-GO) was constructed based on GE11 peptide
      functionalized GO for targeted delivery of oridonin to realize the specific
      recognition of tumour cells and enhance anticancer efficiency. GE11 surface
      modification onto GO significantly increased the cellular uptake of GO in EGFR
      overexpressed oesophageal cancer cells (KYSE-30 and EC109 cells) than that of
      normal cells, indicating the EGFR targeting effects of Ori@GE11-GO. The
      internalized Ori@GE11-GO could accumulate into lysosomes and significantly
      inhibit the viability of cancer cells. Moreover, Ori@GE11-GO could effectively
      induce KYSE-30 and EC109 cells cycle arrest, apoptosis, mitochondrial membrane
      potential (?Psim) disruption through the activation of apoptotic signalling
      pathways and the inhibition of EGFR/Ras/Raf/MEK/ERK signalling pathway, showing
      potential use of Ori@GE11-GO for cancer treatment. Taken together, this study
      demonstrates a good strategy for the construction of bio-functionalized GO drug
      delivery nanosystem to improve the cancer targeting efficiency of anticancer
      medicines.

PMID- 30183383
TI  - Navigating Sex and Sexuality After Sexual Assault: A Qualitative Study of
      Survivors and Informal Support Providers.
AB  - Qualitative interview data from 45 matched pairs of survivors disclosing sexual
      assaults and their primary informal support providers (e.g., friend, family
      member, significant other) were used to explore survivor and support provider
      perspectives on changes in sexuality postassault and how those close to them have
      been affected as a result. Changes in sexuality included loss of interest in sex,
      increase or change in sexual partners, engaging in sex work, and increased sexual
      behavior. Support providers generally regarded promiscuity as a risky sexual
      behavior. If the support provider was the survivor's sexual partner, he or she
      discussed exercising caution when navigating sexual intimacy with the survivor.
      Not all sexual encounters with romantic partners were positive; some survivors
      discussed being triggered (i.e., with post-traumatic stress disorder [PTSD]
      flashbacks) or experiencing the dissolution of their relationships due to the
      sexual impacts of their assault. Counseling implications are discussed in the
      context of improving survivors' sexual experiences in general and in romantic
      relationships postassault. Implications can also be applied to prevention,
      scholarship on sex work, and sexuality research.

PMID- 30183384
TI  - Virally Mediated Overexpression of Glial-Derived Neurotrophic Factor Elicits Age-
      and Dose-Dependent Neuronal Toxicity and Hearing Loss.
AB  - Contemporary cochlear implants (CI) are generally very effective for remediation
      of severe to profound sensorineural hearing loss, but outcomes are still highly
      variable. Auditory nerve survival is likely one of the major factors underlying
      this variability. Neurotrophin therapy therefore has been proposed for CI
      recipients, with the goal of improving outcomes by promoting improved survival of
      cochlear spiral ganglion neurons (SGN) and/or residual hair cells. Previous
      studies have shown that glial-derived neurotrophic factor (GDNF), brain-derived
      neurotrophic factor, and neurotrophin-3 can rescue SGNs following insult. The
      current study was designed to determine whether adeno-associated virus vector
      serotype 5 (AAV-5) encoding either green fluorescent protein or GDNF can
      transduce cells in the mouse cochlea to express useful levels of neurotrophin and
      to approximate the optimum therapeutic dose(s) for transducing hair cells and
      SGN. The findings demonstrate that AAV-5 is a potentially useful gene therapy
      vector for the cochlea, resulting in extremely high levels of transgene
      expression in the cochlear inner hair cells and SGN. However, overexpression of
      human GDNF in newborn mice caused severe neurological symptoms and hearing loss,
      likely due to Purkinje cell loss and cochlear nucleus pathology. Thus, extremely
      high levels of transgene protein expression should be avoided, particularly for
      proteins that have neurological function in neonatal subjects.

PMID- 30183385
TI  - Association between cognitive ability and functional outcomes following traumatic
      brain injury- using a computer-based neurocognitive battery.
AB  - OBJECTIVE: To investigate the contribution of the Cogstate Brief Battery (CBB TM)
      in the explanation of variation of functional outcomes. DESIGN: Secondary
      analysis of the practice-based evidence data set. SETTING: Inpatient
      rehabilitation setting. PARTICIPANTS: Patients (>= 18 years of age) with
      traumatic brain injury who were consecutively admitted to the Toronto
      Rehabilitation Institute between 2008 and 2011 (n = 65). INTERVENTIONS: Not
      applicable Main outcome measure: Cognitive and motor components of the Functional
      Independence Measure. RESULTS: The addition of the CBB TM components resulted in
      a significantly better model for predicting outcomes than a basic model using
      demographics and clinical factors. Among all CBB TM components, speed and
      variation in the identification task and accuracy in the one card learning task
      were significantly associated with cognitive functional outcomes after
      controlling for demographic and clinical factors. Rehabilitation length of stay
      was the only significant clinical factor that was correlated with both cognitive
      and motor outcomes. CONCLUSIONS: Findings of this study suggest the importance of
      considering visual attention and visual memory in predication of cognitive
      outcome and provide valuable information for researchers to consider the specific
      cognitive abilities in functional outcome model in future studies in addition to
      more traditional factors.

PMID- 30183386
TI  - The Src module: an ancient scaffold in the evolution of cytoplasmic tyrosine
      kinases.
AB  - Tyrosine kinases were first discovered as the protein products of viral
      oncogenes. We now know that this large family of metazoan enzymes includes nearly
      one hundred structurally diverse members. Tyrosine kinases are broadly classified
      into two groups: the transmembrane receptor tyrosine kinases, which sense
      extracellular stimuli, and the cytoplasmic tyrosine kinases, which contain
      modular ligand-binding domains and propagate intracellular signals. Several
      families of cytoplasmic tyrosine kinases have in common a core architecture, the
      "Src module," composed of a Src-homology 3 (SH3) domain, a Src-homology 2 (SH2)
      domain, and a kinase domain. Each of these families is defined by additional
      elaborations on this core architecture. Structural, functional, and evolutionary
      studies have revealed a unifying set of principles underlying the activity and
      regulation of tyrosine kinases built on the Src module. The discovery of these
      conserved properties has shaped our knowledge of the workings of protein kinases
      in general, and it has had important implications for our understanding of kinase
      dysregulation in disease and the development of effective kinase-targeted
      therapies.

PMID- 30183387
TI  - The relation between phonological and lexical development in French-speaking
      children.
AB  - This study examines the relation between lexical and phonological variables in 40
      French-speaking children, aged 2;5. Specifically, it examines the influence of
      phonetic complexity, phonological production, phonological memory and
      neighbourhood density (ND) on vocabulary size. Children were divided into four
      groups on the basis of their scores on the French version of the Communicative
      Developmental Inventory (CDI): late1 (< 10%ile), late2 (15-25%ile), middle (40
      60%ile) and precocious (> 90%ile). The children's lexicons were coded in terms of
      phonetic complexity and ND (one-and two-syllable words), and their production
      capacities were determined from measuring percent consonants correct (PCC) and
      the number of syllable-initial (CSI) and -final (CSF) consonants in their
      phonetic inventories. The children also took part in a non-word repetition (NWR)
      task. Results indicated significant group differences in all four sets of
      variables. Children with larger vocabularies selected words with greater phonetic
      complexity and with lower ND values. They had superior PCC, CSI and NWR scores
      compared to children with smaller vocabularies. Linear regression analyses
      indicated that 76% of variance in vocabulary size could be accounted for by ND in
      combination with phonetic complexity and CSI. Our findings are consistent with
      previous studies which show that ND plays an important role in accounting for
      variance in vocabulary size. They also indicate that phonetic complexity and
      phonological production influence lexical acquisition.

PMID- 30183388
TI  - A measure for cluster proximity (MCP) in child speech.
AB  - The proximity of consonant clusters in child speech is measured in the literature
      by the proportion of adult-like produced clusters to targeted clusters. With this
      measure, all clusters that are produced adult-like score 100%, while all others
      score 0%. Consonant clusters in child speech go through three main developmental
      stages: omission, reduction, two-member production (as targeted or substituted).
      Several authors claim that two-member clusters produced as two members should be
      considered acquired whether realised as targeted or not. In view of all these, a
      measure is needed that quantitatively differentiates all possible realisations of
      two-member clusters: omission, reduction, vowel epenthesis, two-member
      production, distinguishing substituted consonants from adult-like ones. Such a
      measure is proposed in the present article. To demonstrate its validity, the
      measure is applied to cluster productions of typically and atypically developing
      monolingual and bilingual children cross-linguistically. Moreover, it is applied
      to a bilingual Greek-English child's consonant clusters at age 2;7, when all
      cluster realisations are present. The aim is for the measure to be used in
      establishing norms for each stage in cluster development which will, in turn,
      guide assessment and intervention in phonologically delayed/disordered children.

PMID- 30183389
TI  - Wet cupping for hypertension: a systematic review and meta-analysis.
AB  - To assess the efficacy and safety of wet cupping in adults with hypertension, we
      conducted a systematic review and meta-analysis using 13 databases. Wet cupping
      alone or in combination with antihypertensive medication or acupuncture was used.
      Seven randomized trials were included, most not of high methodological quality. A
      few small studies suggested that wet cupping alone versus antihypertensive
      medication significantly reduced blood pressure and Traditional Chinese Medicine
      syndrome (hypertension-related symptoms). However based on current evidence, no
      firm conclusions can be drawn and no clinical recommendations made. Research
      projects included need validation. Studies indicate that wet cupping is a safe
      therapy.

PMID- 30183390
TI  - Tear Production Levels and Dry Eye Disease Severity in a Large Norwegian Cohort.
AB  - PURPOSE: To determine if the Schirmer I test (without anesthesia) cut-off value
      is a predictor of dry eye severity in a large Norwegian cohort of dry eye disease
      (DED) patients, which are grouped into six levels of tear production. METHODS:
      Patients (n = 1090) with DED of different etiologies received an extensive dry
      eye work-up: osmolarity (Osm), tear meniscus height (TMH), tear film break-up
      time (TFBUT), ocular protection index (OPI), ocular surface staining (OSS),
      Schirmer I test (ST), meibum expressibility (ME), and meibum quality (MQ).
      Classification of dry eye severity level (DESL) and diagnosis of meibomian gland
      dysfunction (MGD) were also included. The cohort was divided into six groups:
      below and above cut-off values of 5 (groups 1 and 2), 10 (groups 3 and 4), and 15
      mm (groups 5 and 6) of ST. Mann-Whitney test and Chi-Square test were used for
      group comparison of parameters (p <= 0.05). RESULTS: The groups 1, 3, and 5 had
      values indicating more severe DED than the groups 2, 4, 6 with significant
      difference in DESL, Osm, TFBUT, OPI, OSS, and TMH. Regardless of the choice of
      cut-off values, there was no statistically significant difference in ME, MQ, and
      MGD between groups below and above selected cut-off value. When gender difference
      was considered in each group, significant difference was only observed for DESL
      (groups 2, 4, and 5), TFBUT (groups 2, 4, and 5), OPI (groups 2 and 6), and ME
      (group1). CONCLUSIONS: Schirmer I is a robust discriminator for DESL, Osm, TFBUT,
      OPI, OSS, and TMH, but not for ME, MQ, and MGD. Patients with lower tear
      production levels presented with more severe DED at all three defined cut-off
      values. Interestingly, the differences in the mean values of DESL were minimal
      although statistically significant. Thus, the clinical value of different
      Schirmer levels appears to be limited.

PMID- 30183391
TI  - Effect of copper nanoparticles on the mineral content of tissues and droppings,
      and growth of chickens.
AB  - We hypothesised that copper nanoparticles (NanoCu), because of their high
      physicochemical reactivity and bioavailability, could be used in much smaller
      quantities than bulk Cu, consequently reducing excretion of Cu into the
      environment. The objective of the study was to evaluate the effects of various
      levels of NanoCu on the development and growth of broiler chickens, in order to
      establish an optimum level of NanoCu dietary supplementation. Broiler chickens
      were randomly divided into five groups of 10 birds each. The control group
      received 7.5 mg Cu/kg feed (standard level) as CuSO4, while groups fed with
      complexes of NanoCu and starch received 25%, 50%, 75% and 100% of the standard
      level of Cu used in the control group. Chicken growth and excretion of Cu, Fe and
      Zn were measured during the growth period from d 7 to 42. At d 42, the slaughter
      characteristics, the content of Cu, Fe and Zn in the breast muscle and liver, and
      the oxidative status were analysed. The results indicate that using NanoCu can
      reduce the standard level of Cu from CuSO4 supplementation by 75% without
      jeopardising animal growth, and at the same time significantly decreasing Cu
      excretion into the environment.

PMID- 30183392
TI  - Comparative effect of different dietary inulin sources and probiotics on growth
      performance and blood characteristics in growing-finishing pigs.
AB  - The study was focused on assessment of the effect of an extract of long-chain
      inulin (LCI) and dried tubers of Jerusalem artichoke (JA) and a multispecies
      probiotic preparation as well as a combination thereof on growth performance and
      blood parameters of fattening pigs. In total, 144 pigs (initial body weight 30.0
      +/- 0.5 kg) were used in a 98-d experiment. The six dietary treatments consisted
      of the control diet (Con), diet Con supplemented with probiotics (ConP) and four
      diets supplemented with LCI or JA alone or with probiotics (diets LCIP and JAP).
      Throughout the fattening period, there was a beneficial effect of the probiotic
      supplementation to the inulin-containing diets and the average daily gain (ADG)
      was increased by supplementation of probiotics in combination with inulin sources
      (p < 0.05). At the end of the fattening period, ADG and feed conversion ratio
      (FCR) were higher after supplementation of LCI only (p < 0.05). Compared with
      group ConP, in groups LCI and JA, the ADG and FCR were improved (p < 0.05). Only
      in the first fattening stage, the addition of the prebiotics and/or probiotics
      had an impact on the level of white blood cells and some biochemical indices in
      pigs. In younger animals, probiotic or LCI supplementation increased the IgG
      level (p < 0.05). There was also an interaction between the probiotics and JA
      resulting in increased IgG and IgA concentrations (p < 0.05). In the finishing
      period, LCI addition increased the IgM level (p < 0.05), whereas JA addition
      increased IgG and IgM levels as well (p < 0.05). In conclusion, both dietary
      sources of inulin and probiotic supplementation can improve the fattening
      performance and health status of growing pigs.

PMID- 30183393
TI  - Predicting chemical, enzymatic and nutritional properties of fermented barley
      (Hordeum vulgare L.) by second derivate spectra analysis from attenuated total
      reflectance-Fourier transform infrared data and its nutritional value in Japanese
      quails.
AB  - Nutrient concentrations, enzyme activities, viable probiotic counts and organic
      acid levels of fermented barley (FB) produced by solid state fermentation (SSF)
      and of its unfermented counterpart (unfermented barley (UFB)) were determined by
      quantitative methods, and compared with the second derivate spectra analysis
      (SDSA) of their attenuated total reflectance-Fourier transform infrared
      measurements. Moreover, in order to test the nutritional value of FB and UFB
      feeds, 3-d old Japanese quails were fed FB or UFB at 400 g/kg diet for 4 weeks.
      Chemical analysis indicated that FB had significantly increased crude protein,
      ether extract and ash contents, associated with lowered fibre and sugar contents,
      as compared with UFB. IR spectra pattern of FB and UFB samples were similar, but
      their SDSA parameters, particularly peak areas, differed significantly. The
      differences between FB and UFB in peak areas were highly correlated with the
      differences between two feeds in lipid, protein, total fibre, starch and sugar
      contents (p < 0.05). Furthermore, SDSA analysis found new peak areas only
      available in FB samples, indicating fortification with new biomolecules due to
      the effect of SSF. Feeding the FB containing diet for 3 or 4 weeks enhanced
      growth performance significantly and increased the carcass yield of quails,
      indicating its nutritional benefits in young growing quails. The results
      indicated that the further analysis of IR spectra data revealed important
      information on the chemical and biological properties of feed materials, which
      are found to be highly correlated with the results of compositional analysis and
      their biological value in animal model.

PMID- 30183395
TI  - Effect of dietary nitrogen level and source on mRNA expression of urea
      transporters in the rumen epithelium of fattening bulls.
AB  - This paper aims to study the effect of the dietary treatments on mRNA expression
      of urea transporter B (UT-B) and some aquaporins (AQP) in rumen epithelium of
      Italian Simmental young bulls. Eighty animals allocated to 16 pens were fed from
      about 500 to 650 kg body weight with four experimental diets, which resulted from
      the combination of two crude protein levels (125 and 110 g/kg dry matter, diets M
      and L, respectively) and two nitrogen sources (soybean meal (SBM) or SBM partly
      replaced by an isonitrogenous mixture of corn and urea; diets -U and +U,
      respectively). At slaughtering samples of blood and rumen epithelium were
      collected from six bulls for each diet. Blood samples were analysed for
      haematological parameters and quantitative PCR was carried out on the mRNA
      extracted from the rumen epithelium samples. The bulls fed diets M had lower
      plasma concentrations of aspartate aminotransferase than those receiving diets L
      (78.9 vs. 88.3 U/l, p = 0.04). Plasma urea was higher (p = 0.03) for diets M and
      lower for diets +U (2.0 vs. 2.5 and 1.73 vs. 2.00 mmol/l, respectively, in M and
      L diets, p = 0.04). The effect of dietary treatments on rumen UT expression were
      limited to AQP3, which was down regulated (p = 0.01) in diets +U. Finally, a high
      positive correlation (R2 = 0.871) between the expressions of AQP7 and AQP10 was
      found. In conclusion, the AQP3 appears very responsive to dietary treatments and
      therefore it is a candidate to be further studied in rumen metabolism
      experiments. The close relationship between mRNA expression of AQP7 and AQP10
      indicates a similar function of these two proteins.

PMID- 30183394
TI  - Effect of dried corn distillers' grains with solubles and soybean meal
      supplements on physiological indicators and reproductive performance of ewes.
AB  - This study aimed to evaluate the effects of adding dried distillers' grains with
      solubles (DDGS) to the nutritional regimens of ewes at different time periods on
      reproductive traits, serum hormones and serum metabolites. In Experiment 1, 100
      ewes were divided into 4 groups (n = 25) according to diet. The four diets were
      grass hay (H) alone (group H), H with barley (group H + B), H with DDGS for the
      whole feeding period (27 d) (group H + DDGS) or H and DDGS for 5 d (d 8-12 of
      oestrus cycle) (group H + DDGS5). Serum progesterone concentrations were affected
      by oestrus cycle (p < 0.001), but not by dietary treatments. However, feeding H +
      DDGS caused significant increases in serum insulin, leptin and growth hormone
      concentrations (p < 0.05). In Experiment 2, 30 ewes were divided into 2 groups (n
      = 15), receiving DDGS or soybean meal (SBM) during the prepartum period. Diets
      had no significant effect on weights of dams or lambs at birth; however, the
      weaning weights of lambs born from ewes of group DDGS were significantly higher
      (p < 0.05). Moreover, serum glucose, blood urea nitrogen, triglyceride and beta
      hydroxybutyric acid (BHBA) concentrations during the prepartum period were
      affected by dietary treatments and by time (p < 0.001). During the prepartum
      period, BHBA concentrations of ewes fed SBM were higher, while BHBA levels
      decreased during the last weeks of pregnancy regardless of diet. Lamb serum
      immunoglobulin G concentrations increased from 1 h to 24 h after birth (p <
      0.001). Colostrum of ewes fed SBM had higher fat-free dry matter (DM) and protein
      contents in comparison to colostrum of ewes fed DDGS (p < 0.05). In conclusion,
      DDGS can be included as protein source in pregnancy rations up to 15% of DM to
      obtain reproductive performance outcomes equal to or exceeding those obtained
      with SBM.

PMID- 30183396
TI  - Comparison of HBA1c Goals Proposed by an Algorithm To Those Set By Different
      Members of Healthcare Teams Within the Dartmouth Hitchcock Health System.
AB  - OBJECTIVE: An individualized approach is recommended by guidelines when
      establishing hemoglobin A1c (HbA1c) goals. Setting a goal requires experience and
      awareness; it is time consuming and not always trivial. A previous study proposed
      an algorithm for assessing the recommended HbA1c target according to individual
      patient characteristics. Few investigations have explored the variation of HbA1c
      goals recommended among different types of providers. METHODS: We conducted a
      survey regarding practice settings, practices related to diabetes mellitus type
      2, and HbA1c targets recommended to patients. Our objective was to compare HbA1c
      goals between Dartmouth Hitchcock Healthcare System providers (including
      endocrinology department, general internal medicine, and family medicine
      providers) and a previously validated algorithm. The clinical cases presented
      were those used in the previously published study. RESULTS: The survey was sent
      to 228 healthcare providers of whom 81 (35.5%) responded. As recommended by the
      guidelines, healthcare providers individualize their patients' glycemic goals.
      The glycemic goals proposed by the providers in our institution were similar to
      those proposed by the international diabetologists and by the algorithm.
      CONCLUSION: Our results further validate the proposed algorithm within a
      heterogeneous population of healthcare providers. The algorithm could help
      establish glycemic goals and assist healthcare systems in providing more
      standardized care. ABBREVIATIONS: ADA = American Diabetes Association; APRN =
      advanced practice registered nurse; DH = Dartmouth Hitchcock Healthcare System;
      FM = family medicine; GIM = general internal medicine; HbA1c = hemoglobin A1c; PA
      C = certified physician assistant.

PMID- 30183397
TI  - Familial Chylomicronemia Syndrome: A Clinical Guide For Endocrinologists.
AB  - OBJECTIVE: Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive
      disorder caused by mutations in lipoprotein lipase, resulting in accumulation of
      chylomicrons in plasma and hypertriglyceridemia. Elevated triglycerides cause
      several complications in patients, the most serious being episodes of acute
      pancreatitis. This review focuses on expert guidance and opinion from an
      experienced lipidologist and endocrinologist as well as a current review of the
      literature, as there are no specific guidelines on FCS. METHODS: Discussion of
      expert guidance and opinion review of current literature. RESULTS: To date, there
      is no pharmacologic treatment for affected patients, and management options
      primarily include adoption of an extremely restricted, very-low-fat diet, along
      with avoidance of certain medications and alcohol. Endocrinologists often
      diagnose and manage patients with metabolic disorders, including patients with
      high triglyceride levels, but rare diseases like FCS can be missed or poorly
      evaluated due to knowledge gaps about disease state. Given endocrinologists' role
      in the treatment of lipid disorders, it is important that they understand the
      clinical signs and symptoms of FCS to correctly diagnose patients. Patients with
      FCS can be identified based on a defined clinical criteria and a thorough review
      of medical history, after excluding differential diagnoses and secondary factors.
      Typical manifestations include hypertriglyceridemia characterized by lipemic
      serum, history of abdominal pain, and acute/recurrent pancreatitis. Secondary
      factors to be excluded are pregnancy, alcohol abuse, uncontrolled diabetes, and
      use of certain medications. CONCLUSION: FCS is a rare, inherited lipid disorder
      disease that often goes underdiagnosed and unmanaged. This review provides a
      summary of clinical characteristics of FCS that can be potentially used to screen
      patients in an endocrinologist's office and direct them to the appropriate
      standard of care. ABBREVIATIONS: apoB = apolipoprotein B; apoC-III =
      apolipoprotein CIII; ASO = antisense oligonucleotide; FCS = familial
      chylomicronemia syndrome; HTG = hypertriglyceridemia; LPL = lipoprotein lipase;
      LPLD = lipoprotein lipase deficiency.

PMID- 30183398
TI  - Effects of vitamin C supplementation on blood pressure and hypertension control
      in response to ambient temperature changes in patients with essential
      hypertension.
AB  - Evidence for blood pressure-lowering effects of vitamin C (VC) supplementation in
      clinical trials is inconsistent and limited studies have examined the effect of
      VC supplementation on hypertension (HTN) control. In this study, eligible
      patients were cluster assigned to receive 300 mg VC per day or nothing for 6
      months. During the 6-month follow-up period, a questionnaire survey was obtained
      and standardized blood pressure measurements were performed on all subjects. Oral
      administration of VC significantly decreased the diastolic blood pressure and
      pulse pressure with a significant increase in HTN control. After adjusting for
      confounding variables, treatment with VC was associated with ~ 0.5 risk reduction
      of uncontrolled HTN in subjects received anti-hypertensive medications, whereas
      lower indoor and outdoor and ground temperature were significantly associated
      with an increased risk of uncontrolled HTN in all patients. Our results warrant
      further studies investigating the mechanisms underlying the association between
      VC and HTN control.

PMID- 30183399
TI  - Editorial.

PMID- 30183401
TI  - Ferulic acid ameliorated placental inflammation and apoptosis in rat with
      preeclampsia.
AB  - Preeclampsia (PE) occurs specifically during pregnancy characterized by new-onset
      hypertension. The pathogenesis of PE was complicated, and inflammation may be
      central to the pathogenesis of PE. Ferulic acid (FA) is recognized to prevent
      cell damage and apoptosis induced by oxidative stress and inflammation. In our
      study, we used NG-nitro-l-arginine methyl ester (L-NAME)-induced rat model of PE
      to investigate whether FA improved PE and its possible mechanism. We found that
      FA significantly reduced blood pressure, urine volume, and urinary protein level
      in rats with PE. Meanwhile, FA decreased L-NAME induced higher expression of
      circulating TNF-alpha,IL-6,IL-1beta and PlGF, it reduced placental TNF-alpha and
      NF-kappaB p65. Furthermore, FA rescued L-NAME induced decreasing expression of IL
      4 and IL-10 expression in the circulation and placenta of rats. FA also
      ameliorated placental apoptosis in L-NAME induced rats by increasing Bcl-2
      whereas decreasing Bax expression in placenta. It suggested FA as a potential
      candidate for the treatment of various disorders including L-NAME induced
      preeclampsia in rats through decreasing placental inflammation and apoptosis.

PMID- 30183400
TI  - Pulling the covers in electronic health records for an association study with
      self-reported sleep behaviors.
AB  - The electronic health record (EHR) contains rich histories of clinical care, but
      has not traditionally been mined for information related to sleep habits. Here,
      we performed a retrospective EHR study based on a cohort of 3,652 individuals
      with self-reported sleep behaviors documented from visits to the sleep clinic.
      These individuals were obese (mean body mass index 33.6 kg/m2) and had a high
      prevalence of sleep apnea (60.5%), however we found sleep behaviors largely
      concordant with prior prospective cohort studies. In our cohort, average wake
      time was 1 hour later and average sleep duration was 40 minutes longer on
      weekends than on weekdays (p < 10-12). Sleep duration varied considerably as a
      function of age and tended to be longer in females and in whites. Additionally,
      through phenome-wide association analyses, we found an association of long
      weekend sleep with depression, and an unexpectedly large number of associations
      of long weekday sleep with mental health and neurological disorders (q < 0.05).
      We then sought to replicate previously published genetic associations with
      morning/evening preference on a subset of our cohort with extant genotyping data
      (n = 555). While those findings did not replicate in our cohort, a polymorphism
      (rs3754214) in high linkage disequilibrium with a previously published
      polymorphism near TARS2 was associated with long sleep duration (p < 0.01).
      Collectively, our results highlight the potential of the EHR for uncovering the
      correlates of human sleep in real-world populations.

PMID- 30183402
TI  - Risk factors of long-term mortality in middle-aged women: a 27-year follow-up
      cohort.
AB  - OBJECTIVE: This study aimed to evaluate the impact of different risk factors on
      long-term mortality in middle-aged women. METHODS: Women who received preventive
      health care control between 1990 and 1993 were recruited. Anamnesis and physical
      examination were recorded. Blood samples for the measurement of glycemia and
      lipids were taken. Data are reported as of December 2017. RESULTS: We studied
      1197 women aged between 40 and 60 years. We observed 183 deaths (survival 84.0%;
      95% confidence interval [CI], 81.7-86.1, Kaplan-Meier survival analysis). The
      main causes of death were cancer (39.9%; 95% CI, 32.7-47.1), cardiovascular
      disease (22.9%; 95% CI, 16.8-29.1), infectious disease (13.7%; 95% CI, 8.6-18.7),
      other causes (7.1%, 95% CI, 3.4-10.9), and unspecified cause (6.6%; 95% CI, 2.9
      10.2). The final Cox regression model showed the following hazard ratios for
      mortality: diabetes mellitus 2.51 (95% CI, 1.40-4.51), history of fracture 2.47
      (95% CI, 1.15-5.30), history of heart illness 2.06 (95% CI, 1.15-3.72), arterial
      hypertension 1.51 (95% CI, 1.08-2.11), age 1.07 (95% CI, 1.04-1.10), body mass
      index 1.06 (95% CI, 1.02-1.09), and sexual intercourse 0.94 (95% CI, 0.89-0.98).
      Lipid disorders did not reach statistical significance as a risk factor.
      CONCLUSION: Diabetes, a history of fractures, and cardiovascular risk factors,
      except lipids, are markers of long-term mortality in middle-aged women.
      Physicians should pay special attention to these risk factors.

PMID- 30183403
TI  - Storytelling in Acoustic Spaces: Podcasting as Embodied and Engaged Scholarship.
AB  - Health Communication launched the "Defining Moments" feature of the journal in
      2009, including essays that showcase the social and material power of
      storytelling. Over the past 10 years, essays have enlarged academic conventions
      and offered diverse entry points for refiguring the experience of living well in
      the midst of inescapable illness, trauma, and disability. Health Communication
      builds on this legacy by introducing a podcast by the same name. In this essay, I
      position podcasting as embodied and engaged scholarship that connects health
      communication scholars, physicians and other care providers, patients and
      families, and general publics interested in illness and healthcare, vulnerability
      and well-being.

PMID- 30183404
TI  - The Hippo Signaling Network and Its Biological Functions.
AB  - Hippo signaling is an evolutionarily conserved network that has a central role in
      regulating cell proliferation and cell fate to control organ growth and
      regeneration. It promotes activation of the LATS kinases, which control gene
      expression by inhibiting the activity of the transcriptional coactivator proteins
      YAP and TAZ in mammals and Yorkie in Drosophila. Diverse upstream inputs,
      including both biochemical cues and biomechanical cues, regulate Hippo signaling
      and enable it to have a key role as a sensor of cells' physical environment and
      an integrator of growth control signals. Several components of this pathway
      localize to cell-cell junctions and contribute to regulation of Hippo signaling
      by cell polarity, cell contacts, and the cytoskeleton. Downregulation of Hippo
      signaling promotes uncontrolled cell proliferation, impairs differentiation, and
      is associated with cancer. We review the current understanding of Hippo signaling
      and highlight progress in the elucidation of its regulatory mechanisms and
      biological functions.

PMID- 30183405
TI  - Metabolic Gene Clusters in Eukaryotes.
AB  - In bacteria, more than half of the genes in the genome are organized in operons.
      In contrast, in eukaryotes, functionally related genes are usually dispersed
      across the genome. There are, however, numerous examples of functional clusters
      of nonhomologous genes for metabolic pathways in fungi and plants. Despite
      superficial similarities with operons (physical clustering, coordinate
      regulation), these clusters have not usually originated by horizontal gene
      transfer from bacteria, and (unlike operons) the genes are typically transcribed
      separately rather than as a single polycistronic message. This clustering
      phenomenon raises intriguing questions about the origins of clustered metabolic
      pathways in eukaryotes and the significance of clustering for pathway function.
      Here we review metabolic gene clusters from fungi and plants, highlight
      commonalities and differences, and consider how these clusters form and are
      regulated. We also identify opportunities for future research in the areas of
      large-scale genomics, synthetic biology, and experimental evolution.

PMID- 30183406
TI  - H3-H4 Histone Chaperone Pathways.
AB  - Nucleosomes compact and organize genetic material on a structural level. However,
      they also alter local chromatin accessibility through changes in their position,
      through the incorporation of histone variants, and through a vast array of
      histone posttranslational modifications. The dynamic nature of chromatin requires
      histone chaperones to process, deposit, and evict histones in different tissues
      and at different times in the cell cycle. This review focuses on the molecular
      details of canonical and variant H3-H4 histone chaperone pathways that lead to
      histone deposition on DNA as they are currently understood. Emphasis is placed on
      the most established pathways beginning with the folding, posttranslational
      modification, and nuclear import of newly synthesized H3-H4 histones. Next, we
      review the deposition of replication-coupled H3.1-H4 in S-phase and replication
      independent H3.3-H4 via alternative histone chaperone pathways. Highly
      specialized histone chaperones overseeing the deposition of histone variants are
      also briefly discussed.

PMID- 30183407
TI  - Genetic Control of Early Cell Lineages in the Mammalian Embryo.
AB  - Establishing the different lineages of the early mammalian embryo takes place
      over several days and several rounds of cell divisions from the fertilized egg.
      The resulting blastocyst contains the pluripotent cells of the epiblast, from
      which embryonic stem cells can be derived, as well as the extraembryonic lineages
      required for a mammalian embryo to survive in the uterine environment. The
      dynamics of the cellular and genetic interactions controlling the initiation and
      maintenance of these lineages in the mouse embryo are increasingly well
      understood through application of the tools of single-cell genomics, gene
      editing, and in vivo imaging. Exploring the similarities and differences between
      mouse and human development will be essential for translation of these findings
      into new insights into human biology, derivation of stem cells, and improvements
      in fertility treatments.

PMID- 30183408
TI  - Eye tracking as a mean to detect feigned cognitive impairment in the word memory
      test.
AB  - Eye movements showed initial promise for the detection of deception and may be
      harder to consciously manipulate than conventional accuracy measures. Therefore,
      we integrated an eye-tracker with the Word Memory Test (WMT) and tested its
      usefulness for the detection of feigned cognitive impairment. As part of the
      study, simulators (n = 44) and honest controls (n = 41) performed WMT's immediate
      recognition (IR) subtest while their eye movements were recorded. In comparison
      to the control group, simulators spent less time gazing at relevant stimuli,
      spent more time gazing at irrelevant stimuli, and had a lower saccade rate. Group
      classification using a scale that combined the eye movement measures and the
      WMT's accuracy measure showed tentative promise (i.e., it enhanced classification
      compared to the use of the accuracy measure as the sole predictor of group
      membership). Overall, integration of an eye-tracker with the WMT was found to be
      feasible and the eye movement measures showed initial promise for the detection
      of feigned cognitive impairment. Moreover, eye movement measures proved useful in
      enhancing our understanding of strategies utilized by the simulators and the
      cognitive processes that affect their behavior. While the findings are clearly
      preliminary, we hope that they will encourage further research of these promising
      psychophysiological measures.

PMID- 30183409
TI  - The effect of self-care education on the quality of life in children with
      allergic asthma.
AB  - Asthma is a condition where the airways become tiny and swollen producing extra
      mucus. This can cause breathing difficulty and wheezing, coughing, and shortness
      of breath. Self-care education affects the quality of life of children. This
      study examined the effect of self-care education on quality of life for children
      between 8 and 11 years with allergic asthma. This study was a randomized
      controlled trial. Study sample included 70 children between 8 and 11 years with
      asthma allergy referred to Children's Hospital Clinic of Khorramabad, Lorestan
      Province in 2015; they were selected by possible non-consecutive sampling method.
      Children were divided by random sampling of blocks, and classified into two
      groups of 35 patients each in the experimental and control groups. Both groups
      were matched for age and sex of children's and parents' educational level and
      initial quality of life scores were analyzed (using covariance analysis). At the
      beginning, quality of life was calculated by the Pediatric Asthma Quality of Life
      Questionnaire (PAQLQ) for each of the group. The intervention was carried out in
      four sessions of 45 minutes of self-care education for children in the case
      group. No intervention was done in the control group. Eight weeks later quality
      of life was measured in each of the group. There was a significant difference
      between increase values of PAQLQ in the intervention group and control group (p <
      0.001). These results show that self-care education enhances the quality of life
      in asthmatic children.

PMID- 30183410
TI  - Prediction of therapeutic response to pregabalin in subjects with neuropathic
      pain.
AB  - OBJECTIVE: To evaluate four models based on potential predictors for achieving a
      response to pregabalin treatment for neuropathic pain (NeP). METHODS: In total,
      46 pain studies were screened, of which 27 NeP studies met the criteria for
      inclusion in this analysis. Data were pooled from these 27 placebo-controlled
      randomized trials to assess if baseline characteristics (including mean pain and
      pain-related sleep interference [PRSI] scores), early clinical response during
      weeks 1-3 of treatment (change from baseline in pain and PRSI scores), and
      presence of treatment-emergent adverse events (AEs) were predictive of
      therapeutic response. Therapeutic response was defined as a >=30% reduction from
      baseline in either pain and/or PRSI scores at week 5 with supplemental analyses
      to predict pain outcomes at weeks 8 and 12. Predictors of Patient Global
      Impression of Change (PGIC) were also evaluated. Four models were assessed:
      Random Forest, Logistic Regression, Naive Bayes, and Partial Least Squares.
      RESULTS: The number of pregabalin-treated subjects in the training/test datasets,
      respectively, were 2818/1407 (30% pain analysis), 2812/1405 (30% sleep analysis),
      and 2693/1345 (PGIC analysis). All four models demonstrated consistent results,
      and the most important predictors of treatment outcomes at week 5 and pain
      outcomes at weeks 8 and 12 were the reduction in pain score and sleep score in
      the first 1-3 weeks. The presence or absence of the most common AEs in the first
      1-3 weeks was not correlated with any treatment outcome. CONCLUSIONS: Subjects
      with an early response to pregabalin are more likely to experience an end-of
      treatment response.

PMID- 30183411
TI  - The effect of hearing status on speechreading performance of Chinese adolescents.
AB  - The effect of hearing status on the ability to speechread is poorly understood,
      and current findings are inconclusive regarding differences in speechreading
      performance between children and adults with hearing impairment and those with
      normal hearing. In this study, we investigated the effect of hearing status on
      speechreading skills in Chinese adolescents. Thirty seven severely deaf students
      with a mean pure-tone average of 93 dB hearing threshold level and 21 hearing
      controls aged 16 completed tasks measuring their speechreading of simplex finals
      (monophthongs), complex finals (diphthongs or vowel + nasal constellations) and
      initials (consonants) in Chinese. Both accuracy rate and response time data were
      collected. Results showed no significant difference in accuracy between groups.
      By contrast, deaf individuals were significantly faster at speechreading than
      their hearing controls. In addition, for both groups, performance on
      speechreading simplex finals was faster and more accurate than complex finals,
      which in turn was better than initial consonants. We conclude that speechreading
      skills in Chinese adolescents are influenced by hearing status, characteristics
      of sounds to be identified, as well as the measures used.

PMID- 30183412
TI  - Incidence and Characteristics of Low-Speed Vehicle Run-Over Events in Australian
      Aboriginal and/or Torres Strait Islander Children and Other Australian Children
      Aged 0 to 14 Years in Queensland: An 11-Year (1999-2009) Retrospective Analysis.
AB  - The main objective of this study is to describe incidence rates (IRs) of low
      speed vehicle run-over events among children aged 0 to 14 years in Queensland,
      Australia, from 1999 to 2009, by Indigenous Australian status. Data on low-speed
      vehicle run-over events among children aged 0 to 14 years in Queensland were
      obtained for 11 calendar years (1999-2009) from all relevant data sources using
      International Classification of Diseases (ICD) codes, text description, word
      searches, and medical notes and were manually linked. Crude fatal and nonfatal
      IRs were calculated for Indigenous and non-Indigenous children; trends over time
      were analyzed by chi-square test for trend. Relative risks (RRs) were also
      calculated. Data on demographics, health service usage/outcomes, incident
      characteristics, and injury characteristics were obtained. Descriptive and
      multivariate analyses were performed in order to investigate whether these
      characteristics varied with Indigenous status. IRs were higher among Indigenous
      Australian children aged 0 to 14 years (21.76/100,000/annum) than other
      Australian children (14.09), for every year of the 11-year study. The age group
      most at risk for low-speed vehicle run-over events were young children aged 0 to
      4 years, where incidence was 2.13 times greater among Indigenous Australian
      children (95% confidence interval [CI] = 1.67-2.71). There were no significant
      changes in incidence of low-speed vehicle run-overs among Indigenous Australian
      children for 0 to 4, 5 to 9, and 10 to 14 years or overall (0-14 years), during
      the 11-year study period. Over three quarters (n = 107) of low-speed vehicle run
      over events involving Indigenous Australian children occurred outside of major
      cities (43.7% in other Australian children). These data indicate that Indigenous
      Australian children are at increased risk of low-speed vehicle run-over events
      and that characteristics of these events may vary as a function of Indigenous
      status. These results highlight that culturally specific interventions to reduce
      low-speed vehicle run-over events are required.

PMID- 30183413
TI  - Pulmonary Rehabilitation: Where We've Succeeded and Where We've Failed.
AB  - Pulmonary rehabilitation has been established as the standard of care for
      patients with symptomatic chronic obstructive pulmonary disease (COPD). Benefits
      include improvements in exercise tolerance, dyspnoea and quality of life;
      magnitude of benefit is generally greater than for any other COPD therapy. A wide
      range of professional organizations and standards documents have recommended
      pulmonary rehabilitation; benefits accrue across the spectrum of disease
      severity. However, pulmonary rehabilitation is provided to only a tiny fraction
      of those chronic obstructive pulmonary disease (COPD) patients who would benefit.
      International estimates posit that only 1-2% of COPD patients receive pulmonary
      rehabilitation. In contrast, other COPD therapies, bronchodilators and oxygen
      therapy in particular, are much more widely available. The costs of pulmonary
      rehabilitation should not be a major barrier, as costs are comparable to other
      therapies. In seeking strategies to increase pulmonary rehabilitation
      availability, it can be argued that a demonstration of a life prolongation
      benefit would be of great help. Therapies that improve survival have a high
      priority for patients, for their health care providers and for payers. A well
      designed survival study has never been performed. Although efforts are underway
      to organize such a trial, even in a best-case scenario it will be a number of
      years before the results are available.

PMID- 30183414
TI  - Clinician-Facilitated Physical Activity Intervention Versus Pulmonary
      Rehabilitation for Improving Physical Activity in COPD: A Feasibility Study.
AB  - Pulmonary rehabilitation (PR) may not suit all individuals with chronic
      obstructive pulmonary disease (COPD) and may not result in increased physical
      activity. Higher levels of physical activity are associated with reduced
      mortality and morbidity. The aim of this study was to assess the feasibility of
      conducting a trial to investigate the effectiveness of a clinician-facilitated
      physical activity intervention (PAI) versus PR in improving physical activity in
      patients with COPD referred to PR. In this randomised controlled mixed methods
      feasibility study, all patients referred to PR who were eligible and willing were
      assessed at baseline and then randomised to the PAI or to PR. The assessments
      were repeated post-intervention and at 3-month follow-up. The main outcome was
      step count measured by Actigraph. Semi-structured interviews were conducted post
      intervention. The N = 50 patients; mean (SD) age, 64.1(8.6) years, 24M were
      recruited and randomised; N = 23 (PAI) and n = 26 (PR): one patient was excluded
      from the analysis as that person did not meet the GOLD diagnostic criteria. Key
      feasibility criteria were met; recruitment was 11%, dropouts in PAI were 26% (n =
      6) and 50% (n = 13/26) PR. Participants in both groups experienced a range of
      health benefits from their respective programmes. The PAI appears to be effective
      in increasing step counts in people with COPD: mean change (standard deviation)
      [confidence interval] for the PAI group was 972.0(3230.3)[-1080.3 to 3024.4], n =
      12 and 4.3(662.7)[-440.9 to 449.5], n = 11 for the PR group. The PAI met all
      domains of fidelity. This study provides key information to inform a future
      randomised controlled trial in physical activity.

PMID- 30183415
TI  - Calculated Decisions: Wound Closure Classification
AB  - The Wound Closure Classification stratifies types of wounds to help guide
      strategies for closure.

PMID- 30183416
TI  - Assessment of Visual Function in Patients with Myopic Foveoschisis.
AB  - PURPOSE: To assess the visual function in patient with myopic foveoschisis (MF).
      METHODS: Fifty-one eyes of 51 subjects were enrolled and divided into myopic
      foveoschisis group (MFG, N = 16), myopic control group (MCG, N = 18), and normal
      control group (NCG, N = 17) according to their diagnoses. Measurements of the
      logarithm of the minimum angle of resolution (LogMAR), the objective scatter
      index (OSI), the cut-off value of modulation transfer function (COMTF), the
      Strehl ratio (SR), the foveal threshold (FT), and the amplitude density (AD) in
      the first central ring of multifocal electroretinography were recorded and
      compared amongst groups. RESULTS: LogMAR of MFG was the highest (MFG vs. MCG
      p<0.001, MFG vs. NCG p<0.001), and LogMAR of MCG and NCG were similar (p =
      0.258). OSI of MFG was higher than that of MCG (p<0.001), and the latter was
      higher than OSI of NCG (p<0.001). COMTF was lowest in MFG, intermediate in MCG
      and highest in NCG (MFG vs. MCG p = 0.001, MFG vs. NCG p<0.001, MCG vs. NCG
      p<0.001). SR, FT, and AD were all similar between MFG and MCG (p = 0.187, p =
      0.401, and p = 0.446, respectively) while highest in NCG (SR MFG vs. NCG p<0.001,
      MCG vs. NCG p<0.001; FT MFG vs. NCG p = 0.003, MCG vs. NCG p = 0.025; AD MFG vs.
      NCG p<0.001, MCG vs. NCG p<0.001). CONCLUSIONS: Similarities were found between
      various functional parameters from different devices, revealing that the visual
      function in MF patients was impaired.

PMID- 30183417
TI  - Integrated Care in Chronic Obstructive Pulmonary Disease and Rehabilitation.
AB  - Individuals with advanced chronic obstructive pulmonary disease (COPD) often have
      complex medical problems that require more than simple pharmacological therapy to
      optimize outcomes. Comprehensive care is necessary to meet the substantial
      burdens, not just from the primary respiratory disease process itself, but also
      those imposed by its systemic manifestations and comorbidities. These problems
      are intensified in the peri-exacerbation period, especially for newly discharged
      patients. Pulmonary rehabilitation, with its interdisciplinary, patient-centered
      and holistic approach to management, and integrated care, adding coordination or
      transition of care to the chronic care model, are useful approaches to meeting
      these complex issues.

PMID- 30183418
TI  - Coarticulatory dynamics in Greek disyllables produced by young adults with and
      without hearing loss.
AB  - Hearing loss affects both speech perception and production with detrimental
      effects on various speech characteristics including coarticulatory dynamics. The
      aim of the present study is to explore consonant-to-vowel (C-to-V) and vowel-to
      vowel (V-to-V) coarticulation in magnitude, direction and temporal extent in the
      speech of young adult male and female speakers of Greek with normal hearing (NH)
      and hearing impairment (HI). Nine intelligible speakers with profound HI, using
      conventional hearing aids, and five speakers with NH produced /pV1CV2/
      disyllables, with the point vowels /i, a, u/ and the consonants /p, t, s/,
      stressed either on the first or the second syllable. Formant frequencies F1 and
      F2 were measured in order to examine C-to-V effects at vowel midpoint and V-to-V
      effects at vowel onset, midpoint and offset. The acoustic and statistical
      analyses revealed similarities but also significant differences regarding
      coarticulatory patterns of the two groups. Interestingly, prevalence of
      anticipatory coarticulation effects in alveolar contexts was observed for
      speakers with HI. Findings are interpreted on account of possible differences in
      articulation strategies between the two groups and with reference to current
      coarticulatory models.

PMID- 30183419
TI  - Outcomes of spironolactone treatment in patients in Northeast China suffering
      from heart failure with mid-range ejection fraction.
AB  - AIM: The treatment effects of spironolactone on heart failure with reduced (HFrEF
      LVEF <40%) and preserved (HFpEF LVEF >=50%) ejection fraction are well
      characterized. It is not clear whether heart failure patients with mid-range
      ejection fraction (HFmrEF, LVEF 40-49%) benefit from spironolactone. The present
      study aims to evaluate the efficacy of spironolactone in HFmrEF patients. METHOD:
      This study compared a high dosage of spironolactone (50 mg daily), a low dosage
      of spironolactone (25 mg daily), and an untreated group for the prevention of
      major adverse cardiovascular events (MACE) in 279 patients admitted to hospital
      diagnosed with HFmrEF. RESULTS: With a mean follow-up duration of 1 year, the
      death and HF-rehospitalization rate demonstrated significantly lower incidence in
      those taking spironolactone, compared with the untreated group (21.3% vs 34.5%, p
      = .014, respectively). Further analysis showed no difference between two
      spironolactone groups (21.8% vs 20.7%, p = .861). Kaplan-Meier analysis of
      outcome-free survival illustrated a significant difference in survival rate among
      three groups (log-rank testing, p = .045). Compared with the baseline level,
      patients receiving 25 mg spironolactone had a lower physical score (p < .05) at 1
      year follow-up. MLHFQ total scores in the two spironolactone groups markedly
      improved compared with the untreated group (p < .001); similar results were
      observed in the MLHFQ physical scores (p = .025, .001, respectively) and
      emotional sub-scale (p = .023, .011, respectively); however, paired comparison
      between the two spironolactone groups showed no difference. CONCLUSIONS: In
      patients with HFmrEF, treatment with spironolactone significantly reduced the
      incidence of the primary composite outcomes of all-cause death, and
      rehospitalization for the management of heart failure compared with placebo, and
      a high dosage of spironolactone did not show trends of reduction in MACE.

PMID- 30183420
TI  - A local drug delivery system based on visible light-cured glycol chitosan and
      doxorubicin?hydrochloride for thyroid cancer treatment in vitro and in vivo.
AB  - Systemic drug delivery systems (SDDSs) for thyroid cancer treatment are
      associated with serious side effects including nausea, anorexia, and hair loss as
      a result of damage to normal tissues. In this study, we investigated the
      feasibility of a local DDS (LDDS) based on visible light-cured glycol chitosan
      (GC) hydrogel and doxorubicin?hydrochloride (DOX?HCl), called GC10/DOX, on
      thyroid cancer treatment in vivo. Visible light irradiation increased the storage
      modulus and swelling ratio of the GC10/DOX hydrogel precursor. The release of
      DOX?HCl from GC10/DOX exhibited two unique patterns comprising an initial burst
      within 18 hours, followed by a controlled and sustained release thereafter. In
      vitro cell viability testing showed that GC10/DOX had a greater antitumor effect
      than free DOX?HCl and GC10 hydrogel controls. In vivo, local injection of
      GC10/DOX near tumor tissue led to a superior antitumor effect compared with
      controls consisting of free DOX?HCl intravenously injected to the tail vein of
      thyroid cancer-bearing mouse and GC10 hydrogel subcutaneously injected near the
      tumor. Altogether, our results suggest that GC10/DOX may have clinical potential
      for thyroid cancer treatment.

PMID- 30183421
TI  - Treating patients with renal cell carcinoma and bone metastases.
AB  - INTRODUCTION: Bone metastases (BMs) are common and cause morbidity in cancer
      patients. This review focuses on evidence in BMs from metastatic renal cell
      carcinoma (mRCC) management and discusses current evidence on the role of
      systemic treatments in BMs management, bone-targeting agents' benefits in
      skeletal-related events prevention and local therapeutic approaches to BM in
      mRCC. Areas covered: A comprehensive review of literature concerning incidence,
      prognosis, and therapeutic approaches of BMs was performed, focusing on the
      latest emerging evidence in management of BMs from mRCC. Expert commentary: One
      third of mRCC patients present metastatic disease to the bone. BMs impact
      negatively the prognosis and decrease quality of life. Adequate management of BMs
      from RCC requires a multimodal evaluation to optimize care and quality of life.
      Both tyrosine-kinase inhibitors and immunotherapy may be effective in BMs
      treatment. BMs cause severe complications such as fracture, spinal cord
      compression, and pain requiring surgery or radiotherapy and several local
      approaches are available to achieve a local control of the disease. Defining
      prognosis of systemic disease and identifying the main goal of treatment is
      crucial for the selection of the best strategy.

PMID- 30183422
TI  - Relationship between wheelchair skills scores and peak aerobic exercise capacity
      of manual wheelchair users with spinal cord injury: a cross-sectional study.
AB  - PURPOSE: Although both wheelchair skills and fitness are important and probably
      inter-related, the extent and nature of the relationship between them are not
      well understood. The objective of this study was to test the hypothesis that
      there are significant relationships between wheelchair skills scores and the peak
      exercise capacity of community-dwelling manual wheelchair users with spinal cord
      injury. MATERIALS AND METHODS: We studied 26 participants, recording Wheelchair
      Skills Test Questionnaire scores and peak power output from graded aerobic
      wheelchair exercise testing on a motorized treadmill. RESULTS: The median
      Wheelchair Skills Test Questionnaire capacity, confidence, and performance scores
      were 83.3%, 81.5%, and 76.7% and the median peak power output was 58.2 W. On
      regression analysis, there were significant relationships between the total
      Wheelchair Skills Test Questionnaire capacity, confidence, and performance scores
      and peak power output (R2 0.270-0.709, odds ratios 1.043-1.150, p < 0.05).
      CONCLUSIONS: Significant relationships exist between the wheelchair skills
      capacity, confidence, and performance scores and the peak exercise capacity of
      community-dwelling manual wheelchair users with spinal cord injury. These
      findings suggest that both wheelchair skills training and exercise training may
      be useful during the rehabilitation of people with spinal cord injury.
      Implications for rehabilitation Moderate positive relationships exist between
      wheelchair skills capacity and the peak exercise capacity of community-dwelling
      manual wheelchair users with spinal cord injury. Moderate positive relationships
      exist between wheelchair skills confidence and the peak exercise capacity of
      community-dwelling manual wheelchair users with spinal cord injury. Although
      further research is needed, these findings suggest that clinicians should address
      both wheelchair skills training and exercise training during the rehabilitation
      of people with spinal cord injury and not assume that either alone is sufficient.

PMID- 30183423
TI  - Identifying psychosocial difficulties of inpatients with substance use disorders:
      evaluation of the usefulness of the PARADISE24 for clinical practise.
AB  - PURPOSE: Improvements in overall functioning and well-being are important goals
      in the treatment of substance use disorders. The aim of the current study was to
      evaluate the usefulness of the PARADISE24 instrument for studying the scope and
      severity of psychosocial difficulties by comparing the results with other
      measures in the context of substance use disorders. MATERIALS AND METHODS: This
      cross-sectional study included two independent inpatient samples. The first
      sample consisted of 80 interviews including the PARADISE24 and 10 other measures.
      The second sample consisted of the responses of 1082 inpatients to a self
      administered PARADISE24 questionnaire. RESULTS: Inpatients with substance use
      disorders had experienced a wide range of psychosocial difficulties and the two
      samples produced similar results. Highest scores were observed for emotional
      difficulties. The PARADISE24 showed convergent validity with measures of
      disability and depressive symptoms and discriminant validity with personality
      traits and environmental factors (i.e., social support and caretaker's empathy).
      Psychosocial difficulties were inversely associated with quality of life and self
      assessed health. CONCLUSION: The PARADISE24 provides a wide range of useful
      information on psychosocial difficulties for clinical work and it can be used as
      a self-administered questionnaire in the evaluation and treatment of substance
      use disorders. Implications for rehabilitation Individuals undergoing inpatient
      treatment for substance use disorders experience various and severe psychosocial
      difficulties. The PARADISE24 is an evidence-based instrument for assessing the
      scope and severity of 24 common psychosocial difficulties among neurological and
      psychiatric disorders. The PARADISE24 also offers a time-efficient method which
      can be used as a self-administered questionnaire in the context of substance use
      disorders. Comparison between the PARADISE24 and 10 commonly used measures showed
      that the PARADISE24 covered a wide variety of clinically relevant issues in one
      questionnaire.

PMID- 30183424
TI  - Documenting the impact of stroke in a middle-income country: a Malaysian case
      study.
AB  - PURPOSE: Stroke is an abrupt event that often leaves survivors with long term
      disabilities, causing role changes, and financial strains on households. The
      profound impact of stroke on survivors may lead to a decline in quality of life
      due to the physical, psychological, and social difficulties they experience.
      Taking Malaysia as an example, this study aimed to explore the impact of stroke
      on survivors and how health services influence their recovery in low and middle
      income countries (LMIC). METHOD: An ethnographic approach with data obtained
      primarily through in-depth interviews was used. Twenty-seven participants
      identified as having suffered a stroke were drawn from a health and demographic
      surveillance system in Malaysia. RESULTS: The physical and social disruption of
      the lives of stroke survivors was intensified by the resultant financial
      constraints placed upon individuals, families and households, compounded by
      inadequate support from the health, and welfare systems. Despite the disruption
      to their lives, most participants were, at least in part, able to reestablish
      their lives through various factors that include a strong family support and
      active coping strategies. CONCLUSION: In LMIC, recovery can be shaped by the
      family unit and through active coping strategies especially those in relation to
      spirituality. Implications for rehabilitation The impact of stroke on survivors
      and lack of specialized stroke care compromise the recovery process and quality
      of life for stroke survivors in low and middle-income countries. Support from the
      family and reinforcement of religious coping were judged to successfully aid
      recovery. Physical and emotional impairments as well as psychosocial wellbeing of
      survivors in the context of environmental factors need to be addressed.

PMID- 30183425
TI  - Concanavalin-A displays leishmanicidal activity by inducing ROS production in
      human peripheral blood mononuclear cells.
AB  - : The context of the article: Leishmania amazonensis has a wide geographical
      distribution throughout South American countries and can cause self-healing to
      severe cases as mucocutaneous or visceral forms. Leishmaniasis presents a balance
      of inflammatory and anti-inflammatory cytokines which is responsible for
      promoting the activation of phagocytes, essential to control the infection and
      lead to tissue repair/resolution of the disease, respectively. RESULTS AND
      DISCUSSION: Our model revealed that the treatment with Con-A was capable to
      stimulate human PBMC cells by increasing the phagocytic capacity and promoting
      parasite elimination. The pretreatment with Con-A promoted inflammatory (IFN
      gamma, TNF-alpha, IL-2 and IL-6) and anti-inflammatory (IL-4 and IL-10) cytokines
      production, increased the reactive oxygen species (ROS) sinthesys as well as the
      expression and presence of iNOS enzyme, but not nitric oxide production.
      CONCLUSION: Based on the data obtained, it was possible to infer that Con-A
      induces the ROS production, responsible for eliminating parasites in addition to
      regulatory cytokines synthesis which are important for disease resolution.

PMID- 30183426
TI  - Decreased Oleic Acid and Marine n - 3 Polyunsaturated Fatty Acids in Tunisian
      Patients with Urothelial Bladder Cancer.
AB  - Fatty acids (FAs) are thought to impact carcinogenesis by affecting cell
      signaling. A case-control study including 250 patients with urothelial bladder
      cancer (UBC) and 250 controls was conducted. Plasma FAs composition was assessed
      using capillary gas chromatography. Associations of individual and classes of FAs
      with UBC were controlled for the main risk factors for UBC. Plasma FAs profile
      was different in patients compared to controls. Higher levels (third tertile vs.
      first tertile) in palmitic acid (PA) [multi-adjusted OR (95% CI), 1.83 (1.14
      2.92)], and n - 6:n - 3 FA ratio [4.13 (2.38-7.16)] were associated with
      increased risk for UBC [multi-adjusted OR (95% CI), 1.83 (1.14-2.92)]. In
      contrast, higher levels (third tertile vs. first tertile) in oleic [0.54 (0.34
      0.86)], dihomo-gamma-linolenic (DGLA) [0.47 (0.29-0.74)], eicosapentaenoic (EPA)
      [0.32 (0.19-0.52)], and docosahexaenoic (DHA) acids [0.33 (0.20-0.53)] were
      associated with lower risk for UBC. Although the study design does not allow
      proving causality, the findings suggest a possible protective role of oleic acid
      and marine n - 3 polyunsaturated FAs (PUFAs) against bladder carcinogenesis.

PMID- 30183427
TI  - Chunking to improve verbal forward spans in Korsakoff's syndrome.
AB  - Chunking is a mnemonic strategy that involves organizing information into
      appropriate units. Our article examined the use of this strategy on forward and
      backward span performance in Korsakoff's syndrome. Fifteen patients with
      Korsakoff's syndrome and 17 age-and-education matched healthy controls
      participated to the study. Digit span performance (both forward and backward) was
      tested before and after chunking training. Results demonstrated an increased
      performance on the forward spans after chunking training in the patients with
      Korsakoff's syndrome, but no beneficial effect was observed on the backward spans
      in these participants. Controls demonstrated a chunking effect on both forward
      and backward span performance. Our findings suggest that a simple training in
      chunking may be useful as part of a cognitive strategy training for improving
      working memory performance in patients with Korsakoff's syndrome.

PMID- 30183428
TI  - Classification accuracy of the Repeatable Battery for the Assessment of
      Neuropsychological Status (RBANS) Effort Index (EI) and Effort Scale (ES)
      relative to the Test Of Memory Malingering (TOMM) in a mixed clinical sample.
AB  - Performance Validity Testing has become an integral part of neuropsychological
      assessment, and a variety of embedded screening measures for performance validity
      have been proposed. Several performance validity indexes have been developed for
      the Repeatable Battery for the Assessment of Neuropsychological Status. Although
      the RBANS Effort Index (EI) and Effort Scale (ES) have garnered some empirical
      support, other research has raised questions regarding their accuracy in a number
      of assessment contexts. We evaluated the classification accuracy of the EI and ES
      against a standalone performance validity measure (Test of Memory Malingering;
      TOMM) in a mixed clinical patient sample. Our results showed limited utility for
      the ES in a mixed sample and modest classification accuracy for the EI, raising
      concerns about the appropriate scope of use for these scales in general clinical
      practice, which suggested that an alternate EI cutoff score of >0 may be most
      appropriate.

PMID- 30183429
TI  - Geriatric Complex Figure Test: A test for the assessment of planning, visual
      spatial ability, and memory in older adults.
AB  - The present study describes the development of a simplified complex figure for
      older adults. This new figure is based on theoretical organizational strategy
      models developed for the Rey Complex Figure Test and combines several new
      technologies for the enhancement of the data capture. The study shows that the
      accuracy and memory scores for the new measure correlate significantly with Trail
      Making Test, Five Point Test, and RBANS Complex Figure scores. The new figure's
      strategy scores correlate with predominantly nonverbal and to a lesser extent
      with verbal executive functions, supporting the construct validity of these
      scores and illustrating that computer-based data recording methodologies can
      reliably discern the multiple cognitive operations that impact performance on
      this and similar graphomotor measures.

PMID- 30183430
TI  - Electromagnetic transduction therapy and shockwave therapy in 86 patients with
      rotator cuff tendinopathy: A prospective randomized controlled trial.
AB  - Rotator cuff (RC) tendinopathy is the most common cause of shoulder pain. The
      effectiveness of electromagnetic transduction therapy (EMTT), a high energetic
      pulsed electromagnetic field therapy in this field has not been tested yet in
      combination with extracorporeal shock wave therapy (ESWT). A total of 86 patients
      with RC tendinopathy were randomized to undergo three sessions of ESWT in
      combination with 8 sessions of EMTT or sham-EMTT. Both intervention groups
      experienced significant and clinical relevant decrease of pain at all follow-up
      visits, and the functionality of the shoulder evaluated by the Constant Murley
      score increased significantly as well. The combination of EMTT + ESWT produced
      significantly greater pain reduction in the visual analogue scale compared to
      ESWT with sham-EMTT after 24 weeks, during which the Constant Murley score
      improved significantly when the combination of ESWT and EMTT was employed. In
      patients with RC tendinopathy, electromagnetic transduction therapy combined with
      extracorporeal shock wave therapy significantly improves pain and function
      compared to ESWT with sham-EMTT.

PMID- 30183431
TI  - Health professionals' perceptions of the allied health role in the acute setting
      following hip and knee joint replacement surgery: a qualitative study.
AB  - PURPOSE: To describe health professionals' perceptions of the role of allied
      health during the acute phase following elective lower limb joint replacement
      surgery to inform the development of efficient allied health service models.
      METHODS: This was a qualitative descriptive study conducted using semi-structured
      focus groups and thematic analysis. Participants were 25 medical, nursing, and
      allied health professionals working on two orthopaedic wards in a tertiary
      hospital in Victoria, Australia. Focus groups elicited staff perceptions
      regarding the aims and roles of acute allied health intervention following hip
      and knee replacement, how these services are currently provided, and how these
      services can best be provided. This study was undertaken alongside two stepped
      wedge cluster randomised controlled trials during which existing weekend allied
      health services were to be temporarily removed with opportunity to contribute to
      a stakeholder-driven model of these services. RESULTS: The main theme that
      emerged was a sense of unrealised potential amongst health professionals in terms
      of patient outcomes following hip and knee joint replacement surgery arising from
      tension between perceptions of actual versus ideal allied health practice.
      Assessing function and planning for discharge accordingly was perceived to be a
      higher priority than intervening to improve functional independence. CONCLUSION:
      Prioritising allied health intervention to low functioning and complex patients
      could be a more efficient use of allied health expertise in patients following
      lower limb replacement surgery than current practice in this setting that
      prioritises discharge. Implications for Rehabilitation Allied health service
      delivery in the acute phase following hip and knee joint replacement needs to
      balance the needs of the health service with those of the patients. Prioritising
      allied health intervention to low functioning and complex patients could be a
      more efficient use of allied health expertise in this population than current
      practice, which is to prioritise discharge. There may be more scope for nurses to
      be involved in promoting early postoperative mobilisation following joint
      replacement surgery, especially in uncomplicated cases.

PMID- 30183432
TI  - Nursing Students' in Mental Health Nursing Shown by the Debriefing Phase in Low
      Fidelity Simulation.
AB  - There is a lack of documentation about how nursing students evaluate the
      debriefing phase in simulation in mental health nursing. The aim of this
      quantitative study was to describe nursing students' experiences of the
      debriefing phase after low-fidelity simulation activities in mental health
      nursing, and to investigate whether background data influence their experience.
      Data were collected using the "Debriefing Experience Scale" and analysed with
      descriptive and comparative tests. Students with more than 1 year's clinical
      praxis experienced significantly that debriefing helped them to clarify problems
      of communication when encountering persons suffering from psychosis compared to
      students who had less than 1 year of clinical praxis.

PMID- 30183433
TI  - Resistant hypertension in elderly: a clinical manifestation of heart failure with
      preserved ejection fraction? retrospective single-center analysis.
AB  - BACKGROUND: Resistant hypertension (RHT) is defined as high blood pressure
      despite three antihypertensive medications one being a diuretic. RHT is a common
      clinical problem and as a subgroup has not been studied widely. The present study
      has investigated patient demographics and if the RHT might be a clinical
      presentation of heart failure with preserved ejection fraction (HFPEF) in
      elderly. METHOD: The outpatient data between January and June 2015 of Izmir
      Kemalpasa State hospital's hypertension specialty clinic has been reviewed
      retrospectively. The patients with pseudo-RHT are excluded. Among 957 patients,
      68 patients have been identified as true RHT with a left ventricle ejection
      fraction >=50%. HFPEF is defined according to the latest guideline. Instead of a
      common cut-off level for NT-proBNP, age and gender-related cut-off levels have
      been used. RESULTS: The mean age was 63.24 +/- 12.05 years. Among 68 patients, 49
      were female. While only 3 patients in younger group (8.8%) had elevated levels of
      NT-proBNP, 22 of older RHT patients (64.7%) had high levels. NT-proBNP levels
      were disproportionally high in elderly (p < 0.001) and high levels in RHT
      patients were related to a larger left atrial diameter (p < 0.001). CONCLUSION:
      The underlying mechanism might be different in RHT according to age. Hypervolemia
      might be the key factor in older RHT patients but not in younger patients. The
      current study suggests RHT in elderly can be a clinical presentation of HFPEF,
      and they should be investigated and treated accordingly. Because of single-center
      results and limited patients, further studies are needed.

PMID- 30183434
TI  - MTHFD1 promoter hypermethylation increases the risk of hypertension.
AB  - OBJECTIVES: Methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) plays an essential
      role in folate-mediated one-carbon metabolism which determines both homocysteine
      remethylation and de novo thymidylate biosynthesis. Hyperhomocysteinemia is
      positively associated with essential hypertension. This study aimed to
      investigate the association of MTHFD1 promoter methylation with essential
      hypertension. METHODS: Using the quantitative methylation-specific polymerase
      chain reaction (qMSP), the levels of MTHFD1 promoter methylation in 243 essential
      hypertension patients, 218 age- and gender-matched healthy controls. The relative
      changes in serum MTHFD1 promoter methylation were analyzed using the 2
      DeltaDeltaCt method. The percent of methylated reference (PMR) of MTHFD1 was used
      to evaluate the MTHFD1 promoter methylation levels. RESULTS: In our current
      study, the MTHFD1 promoter methylation of hypertensive patients were both higher
      than the healthy control group (median PMR were 8.97% and 5.69%, respectively,
      all p < 0.001). Multivariable analysis showed MTHFD1 promoter hypermethylation
      increase the risk of essential hypertension (OR, 1.336; 95%CI, 1.235-1.446; p <
      0.001). The area under the curve (AUC) of MTHFD1 promoter methylation was 0.739
      in total patients with essential hypertension. CONCLUSIONS: MTHFD1 promoter
      hypermethylation was a potential biomarker for the diagnosis of essential
      hypertension.

PMID- 30183435
TI  - Factors affecting social participation of Iranian children with cerebral palsy.
AB  - The purpose of this study was to identify the factors affecting the social
      participation of Iranian children with cerebral palsy (CP). Participants were 274
      (male = 62%; female = 38%) children with CP, 6- to 12-years old (mean = 1.64) and
      their parents. Several standardized measures were used to assess social
      participation, gather environmental factors, and demographic questionnaires. The
      results of stepwise linear regression analysis indicated that the type of CP,
      Manual ability level and cognitive level (IQ) appear to be strong predictors of
      social participation between personal and environmental factors.

PMID- 30183436
TI  - OPIOIDS: cultivating interprofessional collaboration to find solutions to public
      health problems.
AB  - This study evaluated perceived effectiveness of an interprofessional case-based
      activity that allowed medical and pharmacy students to engage in problem-solving
      around the role of social determinants of health (SDOH) in opioid misuse.
      Students participated in a case-based activity, and then completed a post
      activity survey that included five open-ended questions and the Interprofessional
      Collaborative Competency Attainment Survey. Twelve pharmacy students (100%) and
      47 medical students (75%) completed the post-activity survey. Results indicate
      the activity resulted in a statistically significant increase in student ability
      to: 1) recognize interprofessional team members' knowledge, skills, and
      contributions to the interprofessional team; 2) communicate effectively across
      professions; and 3) learn with, from, and about interprofessional team members to
      develop a patient care plan. Students also reported enhanced understanding of
      treatment considerations with opioid misuse, the role of SDOH, and recognition of
      the value of interprofessional collaboration in their future practice. This
      interprofessional case-based activity appeared to promote collaboration among
      students from different professional programs as they engaged in problem-solving
      around a contemporary public health issue that intersects their future practices.
      This activity may serve as a model for health professional programs,
      practitioners, healthcare systems, and communities that seek interprofessional
      solutions to combat opioid misuse.

PMID- 30183437
TI  - Absolute or relative voice rest after phonosurgery: a blind randomized
      prospective clinical trial.
AB  - OBJECTIVES: The first aim, was to compare participant compliance with
      postoperative voice rest advice in two groups. The second aim was to compare
      vocal function and recovery in the short-term, seven days post-surgery and in the
      long-term, 3-6 months post-surgery. DESIGN: Preliminary randomized prospective
      blind clinical trial. METHODS: Twenty patients scheduled for surgery for benign
      vocal fold lesions were randomized into seven days of absolute or relative voice
      rest. Compliance with voice rest advice was monitored with a voice accumulator
      for seven days following surgery. Vocal recovery was tracked through (a) self
      perceived vocal function, (b) perceptual assessments of voice recordings and (c)
      visual assessment of high resolution and high speed digital imaging (d) vocal
      stamina and reaction to vocal loading, explored with a vocal loading task.
      RESULTS: The absolute voice rest group phonated significantly less than the
      relative voice rest group during seven days post-surgery, but they were not
      silent. The absolute voice rest group self-reported more difficulty with
      compliance than the relative voice rest group. The relative voice rest group
      coped with significantly more vocal loading at long-term check-up. In the short
      term the absolute voice rest group improved morphological recovery to a
      significant degree, however relative voice rest renders superior long-term
      recovery. CONCLUSIONS: Absolute voice rest is difficult to comply with. Neither
      short-term, nor long-term vocal recovery differed significantly between groups.
      Within-group comparisons showed significant improvements in vocal stamina,
      immediate recovery from vocal loading and self-assessments of voice problems only
      for the group with recommended relative voice rest.

PMID- 30183438
TI  - New adalimumab formulation associated with less injection site pain and improved
      motivation for treatment.
AB  - OBJECTIVES: We aimed to evaluate the effect of change to the existing formulation
      of adalimumab (ADA) on pain and treatment motivation. METHODS: We classified
      injection pain into the following categories: overall pain, pain at needle
      insertion, pain during drug injection, and pain 10 min after injection; we
      evaluated the effect of change to the existing formulation on pain using a visual
      analog scale. In addition, a faces pain scale was used to evaluate the effect of
      change in injection pain intensity on treatment motivation. RESULTS: Compared
      with the existing ADA formulation, the new formulation was associated with lower
      scores of overall pain (1.6 vs. 6.7), pain at needle insertion (1.8 vs. 4.7),
      pain during injection (1.6 vs. 7.0), and pain 10 min after the injection (0.4 vs.
      3.1). All results showed a significant difference. p < 0.001. Paired t tests were
      used. In the survey, 68% and 80% of the patients reported injection pain with
      influenza vaccine and the existing formulation, respectively; however, the
      proportion of the patients who experienced pain with the new formulation
      decreased to 20%. CONCLUSIONS: The new ADA formulation may alleviate the burden
      on RA patients and improve the quality of adherence to treatment, thereby
      influencing the RA treatment outcomes.

PMID- 30183439
TI  - Clients' Perspectives of the Effectiveness of Home Modification Recommendations
      by Occupational Therapists.
AB  - This study investigates the effectiveness of home modifications from clients'
      perspectives. Ten participants who received home assessments and modification
      recommendations were recruited from a rehabilitation agency. The dimension of
      home measure and qualitative interviews was conducted. The interviewers were
      transcribed verbatim and analyzed thematically. Participants found home
      modifications improved their safety, accessibility, privacy, and occupational
      performance, especially in performing self-care activities. Occupational
      therapists provided sufficient information and actively involved clients/carers
      in the decision-making process, which contributed to clients' perspectives of
      satisfaction and effectiveness with completed modifications.

PMID- 30183440
TI  - Burnout among Occupational Therapists in Portugal: A Study of Specific Factors.
AB  - This pilot study was conducted using a sample of 374 Portuguese occupational
      therapists to evaluate burnout levels and prevalence among occupational
      therapists as well as to relate those levels to practitioner age, gender, client
      age, years of professional activity, and area of practice. The Copenhagen Burnout
      Inventory questionnaire (Portuguese version) and a sociodemographic questionnaire
      was used. Results showed that ~23%, 44%, and 45% of occupational therapists
      presented with client-related burnout, personal burnout (PB), and work-related
      burnout, respectively. Higher rates of burnout were observed across all
      dimensions as the age of the professionals increased, with more years of working
      increased the client-rated rate, and client age increased the PB rate. Outcomes
      suggest a need to implement intervention programs to promote personal and
      organizational strategies to prevent burnout.

PMID- 30183441
TI  - An antibody fragment against human delta-like ligand-4 for inhibition of cell
      proliferation and neovascularization.
AB  - OBJECTIVES: Angiogenesis targeting is an attractive approach for cancer
      treatment. Delta-like ligand 4 (DLL4) plays a pivotal role in neovascular
      development and its inhibitors have recently entered clinical trials for solid
      tumors. The aim of this study was to evaluate the possibilities of using anti
      DLL4 antibody fragment as an angiogenesis maturation inhibitor. MATERIALS AND
      METHODS: In this study, a DLL4-specific Nanobody, named 3Nb3, was selected and
      assessed by western blotting and internalization assays. Functional assessments
      included MTT, apoptosis, and chicken chorioallantoic membrane (CAM) assays.
      RESULTS: Based on the results, 3Nb3 specifically binds to DLL4 and internalizes
      into MKN cell. Furthermore, 3Nb3 significantly inhibited the proliferation of
      cells and also neovascularization in the CAM. CONCLUSIONS: These data
      demonstrated the potential of Nanobody for application in targeting DLL4. Our
      findings may provide a basis for the development of novel therapeutic techniques
      to inhibit growth and neovascularization of tumors.

PMID- 30183442
TI  - Fanning the Flames: Understanding Gang Involvement Among Philippine Prisoners.
AB  - Utilizing intensive interview and observational data from inmates in one of the
      most overcrowded and underresourced jail in Metro Manila, Philippines, this study
      presents the first in-depth analysis of the factors associated with pangkat
      (prison gangs) and querna (nongang affiliation) membership. The results suggest
      that inmates join pangkats to ensure their safety and survival. In contrast,
      those who remain unaffiliated do so given their negative perceptions of the
      pangkat, sufficient access to social support, and desire to maintain their
      preprison identity. Furthermore, these major themes are situated within a
      modified general strain framework, which integrates traditional models of inmate
      adjustment, namely, deprivation, importation, and coping perspectives. In light
      of these findings, several implications for future research and policy are
      advanced, including the continued application of traditional criminological
      theories for understanding incarcerated populations and the formal integration of
      pangkats to jail administration given the lack of current reform strategies for
      addressing structural and institutional deficiencies.

PMID- 30183443
TI  - Work-related communicative profile of radio broadcasters: a case study.
AB  - PURPOSE: To explore the short-term effect of work-related voice use on voice
      function, and noise exposure on hearing function among radio broadcasters.
      METHOD: A 1-week follow-up study with the participation of two radio broadcasters
      was conducted. Participants were monitored at the beginning and at the end of the
      working week. Premonitoring assessment on Monday (baseline measure) and
      postmonitoring assessment on Friday (follow-up measure) were performed to
      identify short-term effects of work-related conditions on voice and hearing
      function among radio broadcasters. RESULT: Changes in fundamental frequency
      postmonitoring at the end of the work week may be an indication of work-related
      vocal fatigue. Changes in the distribution and standard deviation of SPL during
      the monitoring from Monday to Friday may indicate control of the vocal loudness
      as a strategy to reduce vocal effort during broadcasting. During a 1-week follow
      up, noise conditions during radio broadcasting were below occupational exposure
      limits and without noticeable consequences on hearing function. CONCLUSION: The
      work-related communicative profile of radio broadcasting, from this pilot study,
      suggests that although vocal demands in terms of vocal load may differ among
      broadcasters, the work-related conditions of broadcasting may play a role on
      vocal function among these occupational voice users. Concerning hearing function,
      our results indicate that occupational noise exposure represented minimal risk
      for hearing problems but the consequences of long-term noise exposure on hearing
      mechanisms may yet occur. Future studies with bigger sample sizes are warranted
      to confirm our results.

PMID- 30183444
TI  - Adolescent Males' Understanding of Infertility as a Long-Term Effect of Cancer
      Therapy.
AB  - Cancer therapy can result in infertility in childhood cancer survivors; however,
      little is known about how young adolescent males make sense of infertility and
      potential future parenthood. What's more, research shows that many healthcare
      professionals in Canada do not discuss fertility preservation (FP) with this
      vulnerable population. This study examines how male adolescent childhood cancer
      survivors understand infertility as a long-term effect of cancer treatments. We
      used a narrative analysis to examine 16 interviews with 14-18-year-old males. The
      findings from this research illustrate that FP discussions may raise meaningful
      questions for young men about how they see themselves and construct their
      identities. The findings also demonstrate that young men's beliefs about FP may
      be informed by family narratives, and it shows that biological parenthood may be
      important to adolescent males.

PMID- 30183445
TI  - Unique histopathologic features of the eyelid dermatofibroma.
AB  - PURPOSE: Dermatofibromas are common cutaneous lesions, but rarely occur in the
      eyelid skin. The reason for the low incidence in the palpebral skin has not been
      elucidated. In this study, we analyze the histopathologic features of an
      illustrative case of dermatofibroma and review previously published cases to
      determine whether eyelid dermatofibroma develops differently from the
      prototypical dermatofibroma. METHODS: Histopathologic analysis of a new
      illustrative case of eyelid dermatofibroma and retrospective review of published
      cases. RESULTS: The distinguishing features of the illustrative lesion included a
      rounder gross appearance, nonacanthotic epithelium, basophilic staining, cellular
      character, and a paucity of "collagen trapping." These features deviated from the
      typical features associated with classic dermatofibroma. Review of the 11
      previously published cases of eyelid dermatofibroma revealed that they were more
      similar in appearance to the illustrative lesion than to classic dermatofibroma.
      DISCUSSION: The rarity and histological deviations of the eyelid dermatofibroma
      suggest that the dermal substrate from which the lesion develops differs from
      that of the classic dermatofibroma. This difference may be explained
      microanatomically based on the fact that the dermis of the eyelid is
      predominantly papillary, whereas the dermis of extrapalpebral skin where
      dermatofibromas are more common is predominantly reticular. CONCLUSIONS: Although
      related, eyelid dermatofibromas appear to be histologically distinct from classic
      dermatofibromas, owing to the unique dermal composition of the site of origin.

PMID- 30183446
TI  - Personal reflections on the early contributions of Gus Born to platelet research.
AB  - Professor GVR Born, Gus to his friends, was one of the great pioneers of platelet
      research. My early memories of him have enabled me to look back at his early
      years in Oxford and London. A brilliant and generous man with always the time to
      discuss and advise he was instrumental in deciphering the principle stages of the
      aggregation of blood platelets by ADP, a path aided by his development and use of
      the platelet aggregometer. He applied his knowledge to the real time analysis of
      platelet and leukocyte involvement in thrombus formation in animal models and to
      the development of atherosclerosis and thrombosis and their pharmacological
      inhibition. What follows is a personal account of the major steps in this early
      work and of the actors involved.

PMID- 30183447
TI  - Botulism Outbreak in a Regional Community Hospital: Lessons Learned in Transfer
      and Transport Considerations.
AB  - : Botulism is a potentially lethal disease caused by a toxin released by
      Clostridium botulinum. Outbreaks of botulism from food sources can lead to a Mass
      Casualty Incident (MCI) involving sometimes hundreds of individuals. We report on
      a recent outbreak of botulism treated at a regional community hospital with a
      focus on emergency medical services (EMS) response and transport considerations.
      CASE PRESENTATION: There were 53 patient evaluated for botulism at the sending
      facility. In total, 11 botulism exposures required intubation at the sending
      facility. Twenty-four patients were ultimately transported by critical care
      capable ALS crews with the majority (16) of these transports occurred in the
      first 24 hours. There was one fatality in the first days of the outbreak and a
      second death that occurred in a patient who died after long-term acute care
      (LTAC) placement several months after hospital discharge. CONCLUSION: Local EMS
      providers and public safety officers have a critical role in identifying and
      following up on potentially exposed botulism cases. The organization of
      transporting agencies and the logistics of transfer turned out to be 2
      opportunities for improvement in response to this mass casualty incident.

PMID- 30183448
TI  - Decision-Making in the Moments Before Death: Challenges in Prehospital Care.
AB  - BACKGROUND: The primary charge of Emergency Medical Services (EMS) is to save
      lives. However, EMS personnel are frequently called to scenes where prolonging
      life may not be the primary goal. When someone is nearing death, family members
      may feel compelled to call 9-1-1 because they are feeling uncertain about how to
      manage symptoms at the end of life. OBJECTIVE: We sought to explore prehospital
      providers' perspectives on how the awareness of dying and documentation of end-of
      life wishes influence decision-making on emergency calls near the end of life.
      METHODS: The study design was exploratory, descriptive, and cross-sectional.
      Qualitative methods were chosen to explore participants' perspectives in their
      own words. In-depth in-person interviews were conducted with 43 EMS providers.
      Interviews were audio recorded and professionally transcribed. Interview
      transcripts were entered in Atlas.ti for data management and coding. The analysis
      was deductive and guided by a conceptual model of 4 contexts of end-of-life
      decision-making that is not setting-specific, but has been applied to prehospital
      care in this study. RESULTS: The findings illustrate the relationship between
      awareness of dying and documentation of wishes in EMS calls. The 4 decisional
      contexts are: (1) Awareness of Dying-Wishes Documented: Families were prepared
      but validation and/or support was needed in the moment; (2) Awareness of Dying
      Wishes Undocumented: EMS must initiate treatment, medical control guidance was
      needed; (3) Unaware of Dying-Wishes Documented: Shock, expectation that EMS can
      stop the dying; and (4) Unaware of Dying-Wishes Undocumented: Families were
      unprepared, uncertain, frantic. Each context is illustrated by representative
      quotes from participants. Discordance and conflict was found in each decisional
      context. CONCLUSIONS: This study illustrates that EMS providers are acutely aware
      of the impact of their decisions and actions on families at the end of life. How
      emergency calls near the end of life are handled influences how people die,
      whether their preferences are honored, and the appropriate use of ambulance
      transport and ED care. The findings highlight how the intersection of awareness
      of dying and documentation of wishes influence prehospital decision-making in end
      of-life emergencies and demonstrate the key role EMS providers have in this
      critical period.

PMID- 30183449
TI  - Increased Anticolitic Effects in C57BL/6 Mice Based on Functional Ingredients of
      Ramyeon Noodles and Soup.
AB  - We investigated the preventive effects of Ramyeon made from brown rice-sorghum
      noodles and doenjang-bamboo salt soup (BS+DB) on colitis induced by dextran
      sulfate sodium (DSS) in C57BL/6 mice. Noodles were prepared with 10% brown rice
      and 10% sorghum powders added to wheat flour and potato powder, and soup was made
      using starter fermented (SF) doenjang powder (32%) and bamboo salt (13.5%). The
      experimental animals were divided into five groups: Normal, Control, BS (brown
      rice and sorghum noodles)+DB (doenjang and bamboo salt soup) (BS+DB Ramyeon), W
      (white flour noodles, commercial one)+DB, W+dC (W+doenjang commercial soup), and
      W + D (W+SF doenjang powder [100%]). The BS+DB and W + D groups showed
      significant reduction of DSS-induced colitis symptoms (P < .05). Doenjang soup
      (100%) (W+D) also showed a strong anticolitic effect even though the noodles were
      prepared with W. Histological observation of the colon revealed that BS+DB
      Ramyeon markedly alleviated colitis development in mice. Serum protein and mRNA
      levels of proinflammatory cytokines (TNF-alpha, IL-1beta, and IL-6) were
      significantly suppressed in colon tissue of the BS+DB group compared with those
      of the W+DB and W+dC groups. BS+DB Ramyeon also reduced colon mRNA levels of
      inducible nitric oxide synthase and cyclooxygenase-2 compared with those of other
      groups (P < .05). Our results show that modification of noodle ingredients using
      brown rice and sorghum as well as alteration of soup composition using doenjang
      and bamboo salt improved the health benefits of Ramyeon.

PMID- 30183450
TI  - Case marking in German-speaking children with specific language impairment and
      with phonological impairment.
AB  - Identification of children with specific language impairment (SLI, now known as
      Developmental Language Disorder) remains challenging. Morphosyntax difficulties
      have been proposed as potential linguistic 'markers' for SLI across a number of
      languages. This study investigates the existence of such a clinical marker in
      German-speaking children with SLI, looking in particular at German case marking,
      and makes comparisons with matched typically developing groups and a group with
      isolated phonological impairment (PI). A case-control study was completed with 66
      pre-school children in four groups (1) SLI, (2) PI, (3) age-matched typically
      developing children (TD-A) (4) language-matched typically developing children (TD
      L). Errors in nominative, accusative and dative marking were analysed from the
      production of articles in elicitation tasks and spontaneous language samples. The
      performance of the SLI group was poorer than the TD-A group across all three
      grammatical cases investigated, but there was little supportive evidence for this
      being a diagnostic marker. It is, however, suggested that poor case marking may
      alert clinicians to the need for further linguistic assessment. No significant
      differences were found between the SLI and PI groups; rather scores for the PI
      group suggested they fell on a gradient between the SLI TD-A groups. Findings are
      discussed in relation to the proposed new diagnostic category of developmental
      language disorder.

PMID- 30183451
TI  - Clinical pertinence of neutrophil-to- lymphocyte ratio among hypertensives with
      different grades and duration of hypertension - an insight.
AB  - : Over the recent years, the pathophysiology of the inflammatory component in
      hypertension has been a challenge, because this inflammatory response is mainly
      contributed by an increased oxidative stress with the release of inflammatory
      mediators. Identification of a simple and early inflammatory marker such as the
      neutrophil-to-lymphocyte ratio (NLR) is the need of the hour. This study
      correlates the same specifically taking into account the duration and the grades
      of hypertension. OBJECTIVE: The response of the NLR among the hypertensives and
      its correlation with duration and stages of hypertension. METHOD: Totally, 80
      subjects and 40 controls of age between 20 and 60 years and both genders were
      included. Three recordings of blood pressure were measured with a standard
      mercury sphygmomanometer. The differential leukocyte count was estimated with an
      automated Beckman Coulter. OBJECTIVE: Variations in the neutrophil and lymphocyte
      counts were significant among the hypertensives with a p-value < 0.001. The NLR
      was also significantly altered among the hypertensives with a p-value = 0.001.
      The NLR showed a rise in value among the normotensives, prehypertensives, and
      stage 1 of systolic hypertension, though not statistically significant. An
      increase in the NLR was observed in hypertensives with duration of 1-2 years.
      CONCLUSION: Our study gives a new insight with a rise in NLR in early years and
      even among prehypertensives and stage 1 systolic hypertension under strict
      criterion. This could be utilized as an early predictive tool, relating the
      inflammatory process and hypertension which on further intervention could slow
      the progression of the disease process. ABBREVIATIONS: NLR: Neutrophil-to
      lymphocyte ratio; BP: Blood pressure.

PMID- 30183452
TI  - Platelet microparticles-containing miR-4306 inhibits human monocyte-derived
      macrophages migration through VEGFA/ERK1/2/NF-kappaB signaling pathways.
AB  - Platelets are major sources of microparticles (MPs) in peripheral bloodstream,
      and platelet-secreted MPs (P-MPs) transfer biological information to neighboring
      cells. In the present study, we found that the platelet- and P-MPs-derived
      microRNA-4306 (miR-4306) expression were downregulated in coronary artery disease
      (CAD) and platelet-derived miR-4306 was an independent poor prognostic factor in
      CAD. Plasma miRNA-4306 mainly cofractionated with MPs instead of Argonaute2
      complexes or HDL. P-MPs could effectively deliver miR-4306 into human monocyte
      derived macrophages (HMDMs). MiR-4306 noticeably inhibited the HMDMs migration in
      vitro and reduced the number of macrophage cells in cardiac tissue in myocardial
      infarction mice. This functional impact of miR-4306 was mediated directly through
      VEGFA to inhibit ERK/NF-kappaB signaling. In conclusion, our study suggested that
      intercellular transfer of miR-4306 by platelet microparticles inhibited the HMDMs
      migration through VEGFA/ERK1/2/NF-kappaB signaling pathways.

PMID- 30183453
TI  - Effects of integrating Neurac vibration into a side-lying bridge exercise on a
      sling in patients with chronic low back pain: a randomized controlled study.
AB  - PURPOSE: This study examined the effects of integrated Neurac vibration during
      side-lying bridge exercise using a sling system on pain, strength, and balance in
      patients with chronic low back pain (LBP). SUBJECTS AND METHODS: A total of 30
      patients were randomly assigned to experimental (EG; n = 15) or control groups
      (CG; n = 15). Both groups performed side-lying bridge exercise; however, the EG
      group also received Neurac vibration during exercise. Outcome measures included
      perceived pain level, asymmetry of weight distribution, asymmetry of hip abductor
      strength (AHAS), and static balance in one-leg standing. A 2 * 2 repeated
      measures analysis of variance was used to determine main effects and interaction
      for each parameter. RESULTS: Significant interaction effects were found between
      group and time factors for all parameters. Between-group comparisons revealed
      significant differences in observed changes for all parameters (P < 0.05). In
      within-group comparisons, EG showed significant changes in all parameters after
      intervention (P < 0.05); however, significant changes were only found for pain
      and AHAS in the CG (P < 0.05). Pain score showed greatest effect size (d = 0.77)
      among all parameters, indicating a moderate effect of intervention. CONCLUSION:
      The side-lying bridge exercise on a sling system may alleviate pain and improve
      strength and balance in patients with chronic LBP, with more favorable effects
      when Neurac vibration is integrated into the exercise plan.

PMID- 30183454
TI  - Lacrimal drainage anomalies in Rubinstein-Taybi syndrome: case report and review
      of literature.
AB  - Rubinstein-Taybi syndrome is a rare multisystem disorder characterized by broad
      thumbs and first toes, short stature, microcephaly, delayed milestones, beak
      nose, and hypertelorism. Lacrimal drainage anomalies are not uncommon in this
      syndrome. We present a patient with Rubinstein-Taybi syndrome with bilateral
      congenital nasolacrimal duct obstruction and left-sided grossly dilated
      nasolacrimal duct.

PMID- 30183455
TI  - A guide to designing a naming test for an under-researched bilingual population:
      adapting the Boston Naming Test to Tongan.
AB  - The purpose of this paper is to provide guidelines on how to develop a naming
      test for an under-researched language, through adaptation of an English test. An
      additional consideration is how to make an assessment suitable for bilinguals.
      While test development involves a number of phases, the focus in this research is
      on test construction. To illustrate the steps required for this, a Tongan
      adaptation of the Boston Naming Test (BNT) for Tongan-English bilinguals is
      discussed. In the adaptation, language structure and cultural appropriateness are
      considered in item selection. This version retains just 7 of the original BNT
      words and includes 15 words of particular importance in Tongan culture. As the
      items in the BNT are ordered according to naming difficulty, the authors also
      consider how to determine graded difficulty for Tongan words, in the absence of a
      Tongan corpus or established information on word frequency/difficulty. This issue
      is resolved by asking Tongan-English bilinguals (n = 20) to rate a list of 175
      words for frequency and familiarity. From this set, 120 words were then selected
      and presented as a picture naming assessment to an additional group of bilinguals
      (n = 42). Their responses were analysed according to accuracy and speed. A final
      list of 70 words with pictures was ordered on the basis of these responses for
      the next step of testing.

PMID- 30183456
TI  - Managing cancer risk in patients with systemic lupus erythematous.
AB  - INTRODUCTION: Numerous studies have clearly demonstrated that there is an altered
      cancer risk profile in patients with systemic lupus erythematous (SLE) versus the
      general population. This includes a higher risk of certain cancers (e.g.
      hematologic, lung) and a decreased risk of others (e.g. breast cancer). Several
      determinants could be behind this altered risk; these include immunosuppressant
      drugs, viral exposures, genetic factors, and other variables. Area covered: We
      review what is known regarding specific risk profiles and risk factors for some
      key cancers in SLE, including hematologic malignancies and lung cancers. In light
      of this, we examine current guidelines and practices regarding cancer screening,
      and propose ways that patients and physicians might help manage cancer risk in
      SLE. Expert commentary: Despite significant progress over the past decade, not
      many risk factors have been precisely identified. A better understanding of the
      elements that drive malignancy risk in systemic autoimmune rheumatic diseases may
      permit the further development of guidelines (regarding. cancer screening) for
      SLE patients. ABBREVIATIONS: AbTG: Anti-thyroglobulin antibodies; AbTPO: Anti
      peroxydase antibodies; AML: Acute myeloid leukemia; APRIL: A proliferating
      inducing ligand; BAFF: B-cell activating factor; CAPA: Canadian Arthritis Patient
      Alliance; CI: Confidence interval; CIN: Cervical intraepithelial neoplasia; CT:
      Computed tomography; DLBCL: Diffuse large B cell lymphoma; dsDNA: Double-stranded
      DNA; EBV: Epstein-Barr virus; EULAR European League Against Rheumatism; IBD:
      Inflammatory bowel disease; HBV: Hepatitis B virus; HCV: Hepatitis C virus; HIV:
      Human immunodeficiency virus; HR: Hazard ratio; HSIL: High-grade cervical
      squamous intraepithelial lesions; HSV: Herpes simplex virus; HL: Hodgkin
      lymphoma; HPV: Human papillomavirus; MALT: Mucosa-associated lymphoid tissue;
      MDS: Myelodysplastic syndrome; MESNA: 2-mercaptoethane sodium sulfonate; NHL: Non
      Hodgkin lymphoma; OR: Odds ratio; Pap: Papanicolaou; RA: Rheumatoid arthritis;
      SLE: Systemic Lupus erythematous; SLICC: Systemic International Collaborating
      Clinics; SNPs: Single-nucleotide polymorphisms; SOGC: Society of Obstetricians
      and Gynaecologists of Canada.

PMID- 30183459
TI  - A novel mutual information estimator to measure spike train correlations in a
      model thalamocortical network.
AB  - The impact of thalamic state on information transmission to the cortex remains
      poorly understood. This limitation exists due to the rich dynamics displayed by
      thalamocortical networks and because of inadequate tools to characterize those
      dynamics. Here, we introduce a novel estimator of mutual information and use it
      to determine the impact of a computational model of thalamic state on information
      transmission. Using several criteria, this novel estimator, which uses an
      adaptive partition, is shown to be superior to other mutual information
      estimators with uniform partitions when used to analyze simulated spike train
      data with different mean spike rates, as well as electrophysiological data from
      simultaneously recorded neurons. When applied to a thalamocortical model, the
      estimator revealed that thalamocortical cell T-type calcium current conductance
      influences mutual information between the input and output from this network. In
      particular, a T-type calcium current conductance of about 40 nS appears to
      produce maximal mutual information between the input to this network
      (conceptualized as afferent input to the thalamocortical cell) and the output of
      the network at the level of a layer 4 cortical neuron. Furthermore, at particular
      combinations of inputs to thalamocortical and thalamic reticular nucleus cells,
      thalamic cell bursting correlated strongly with recovery of mutual information
      between thalamic afferents and layer 4 neurons. These studies suggest that the
      novel mutual information estimator has advantages over previous estimators, and
      that thalamic reticular nucleus activity can enhance mutual information between
      thalamic afferents and thalamorecipient cells in the cortex.

PMID- 30183458
TI  - El Nino Altered Gut Microbiota of Children: A New Insight on Weather-Gut
      Interactions and Protective Effects of Probiotic.
AB  - Changes in weather often trigger a myriad of negative impacts on the environment,
      which eventually affect human health. During the early months of 2016, Malaysia
      experienced El Nino, with an extremely dry season of almost zero rainfall. At the
      same time, an increase of more than twofold in fecal secretary immunoglobulin-A
      (SIgA) levels of healthy preschool children aged 2-6 years was observed,
      accompanied by an increase in phylum Bacteroidetes, predominantly attributed to
      genus Bacteroides and Odoribacter, which also positively correlated with fecal
      SIgA levels. Here, we present evidence to illustrate the detrimental effects of
      weather change on a microscopic "environment," the human gut ecosystem. We also
      discuss the protective effects of probiotic against dysbiosis as induced by
      weather change. The increase in Bacteroidetes was at an expense of decreased
      genus Faecalibacterium and Veillonella (phylum Firmicutes), whereas children
      consuming probiotic had a decrease in genus Collinsella, Atopobium, and
      Eggerthella (phylum Actinobacteria) instead.

PMID- 30183457
TI  - Perceived Risks and Benefits in IPV and HIV Research: Listening to the Voices of
      HIV-Positive African American Women.
AB  - African American women living with HIV were asked to reflect on the perceived
      risks and benefits of research participation after completing a study examining
      socially sensitive issues in their lives, including intimate partner violence
      (IPV) and HIV. Administration of standardized quantitative instruments yielded
      positive responses to the research experience. However, qualitative assessments
      of perceived risks and benefits revealed more nuanced responses. For example,
      confidentiality concerns were more prominent in open-ended responses as was
      participants' positive attitudes toward monetary compensation. In addition, some
      women reported that study participation provided them with new insights about
      their experiences with IPV. Findings suggest that empirical studies on research
      protections involving potentially distressing and socially sensitive experiences
      with vulnerable populations require both quantitative and qualitative assessments
      of perceived risks and benefits. We discuss implications of our findings for
      ethics practices in trauma-related research among populations with multiple
      social vulnerabilities.

PMID- 30183460
TI  - Opposing mechanisms underlying differential changes in brain oxygen and
      temperature induced by intravenous morphine.
AB  - Morphine remains widely used in clinical settings due to its potent analgesic
      properties. However, one of the gravest risks of all opioids is their ability to
      induce respiratory depression and subsequent brain hypoxia that can lead to coma
      and death. Due to these life-threatening effects, our goal was to examine the
      effects of intravenous (iv) morphine at a wide range of doses (0.1-12.8 mg/kg) on
      changes in brain oxygen levels in freely-moving rats. We employed oxygen sensors
      coupled with high-speed amperometry and conducted measurements in the nucleus
      accumbens (NAc) and subcutaneous (SC) space, the latter serving as a proxy for
      blood oxygen levels that depend on respiratory activity. Morphine induced dose
      dependent decreases in SC oxygen levels, suggesting respiratory depression, but
      differential effects on NAc oxygen: increases at low and moderate doses (0.1-1.6
      mg/kg) and decreases at high doses (6.4 mg/kg). We also examined the effects of
      morphine on NAc, muscle, and skin temperature. Morphine increased brain
      temperature at low and moderate doses but induced a biphasic, down-up change at
      high doses. The oxygen increases appear to result from a neurovascular coupling
      mechanism via local vasodilation and enhanced oxygen entry into brain tissue to
      compensate for blood oxygen drops caused by modest respiratory depression. At
      high morphine doses, this adaptive mechanism is unable to compensate for the
      enhanced respiratory depression, resulting in brain hypoxia. Hence, morphine
      appears to be safe when used as an analgesic at clinically relevant doses, but
      poses great risks when abused at high doses.

PMID- 30183461
TI  - Cordycepin ameliorates skin inflammation in a DNFB-challenged murine model of
      atopic dermatitis.
AB  - OBJECTIVES: Atopic dermatitis (AD) is an allergic and inflammatory skin disorder
      caused by a combination of itching and skin sensitization by allergens. This
      article investigated whether cordycepin modulates AD symptoms by using an AD
      murine model. MATERIAL AND METHODS: We evaluated a regulatory effect and specific
      molecular mechanism of cordycepin on AD induced by the repeated local exposure of
      2,4-dinitrochlorobenzene to dorsal skin of mice. Blood or AD-like skin lesions
      samples were removed for histopathologic analysis, enzyme-linked immunosorbent
      assay, reverse transcription-polymerase chain reaction, and Western blot
      analyses. RESULTS: Oral administration of cordycepin decreased duration of
      scratching behavior and serum levels of histamine and immunoglobulin E increased
      by DNFB challenge. Cordycepin attenuated clinical symptoms and epidermis
      thickness of AD mice. In addition, cordycepin reduced thymic stromal
      lymphopoietin (TSLP), interleukin (IL)-4, IL-6, and tumor necrosis factor-alpha
      levels in the serum of AD mice. Cordycepin-attenuated infiltrations of mast cells
      and eosinophils with decreases in TSLP, macrophage inflammatory protein-2, and
      intercellular adhesion molecule-1 protein levels in AD-like skin lesions.
      Messenger RNA expressions of TSLP, thymus and activation-regulated
      chemokine/CCL17, and C-C chemokine receptor type 3 in AD-like skin lesions were
      also suppressed by cordycepin. Cordycepin inhibited caspase-1 expressions and
      activities in AD-like skin lesions. CONCLUSIONS: In conclusion, this study
      demonstrates that cordycepin ameliorates AD symptoms, suggesting that cordycepin
      might be a candidate to treat allergic skin diseases.

PMID- 30183462
TI  - Association Between Migraine and Breast Cancer Risk: A Population-Based Cohort
      Study and Literature Review.
AB  - OBJECTIVE: Previous case-control studies have suggested that women with migraine
      have lower risk of developing breast cancer, but conflicting results were noted
      in cohort studies. We investigated the association between migraine and breast
      cancer incidence in a nationwide population-based cohort study. METHODS: We
      identified 25,606 women with migraine between 2000 and 2013 from the National
      Health Insurance Research Database in Taiwan. Each migraineur was randomly
      frequency matched with four women without migraine by age and index year of
      migraine diagnosis. Cox's proportional hazard regression analysis was performed
      to estimate the association between migraine on the risk of developing breast
      cancer. RESULTS: With a mean follow-up of 7.3 years, 234 and 978 breast
      malignancies occurred in the migraine cohort and matched cohort, respectively.
      Migraine was not associated with the risk of breast cancer (adjusted hazard ratio
      = 1.03, 95% confidence interval = 0.89-1.21). Among women with migraine,
      independent risk factors for breast cancer included older age, alcohol-related
      illness, and receipt of a greater number of breast cancer screening examinations,
      and independent protective factors included the use of antihypertensive agents,
      statins, and nonsteroidal anti-inflammatory drugs. Further analyses indicated
      that women with >=4 medical visits for migraine per year had a significantly
      greater risk of breast cancer than the matched cohort. CONCLUSIONS: Migraine was
      not associated with a decreased risk of developing breast cancer among Taiwanese
      women. Further prospective studies on other geographic populations or on the
      association between migraine frequency and the risk of developing breast cancer
      are warranted to validate our findings.

PMID- 30183463
TI  - Self-Care System for Family Caregivers of Cancer Patients Using Resonant
      Breathing with a Portable Home Device: A Randomized Open-Label Study.
AB  - BACKGROUND: Self-care systems for early-stage specialist palliative care for
      cancer patients and their family caregivers have received much attention
      recently. Resonant breathing is an established method for maximizing heart rate
      variability (HRV), but it has not been implemented for home self-care. OBJECTIVE:
      We aimed to examine the usefulness and ease of implementation for family
      caregivers to administer resonant breathing using a portable device at home.
      DESIGN: We divided caregivers into two groups-a home self-care group and a
      control group-and we conducted a randomized open-label study, with rate of change
      in HRV being the primary outcome. SETTING/SUBJECTS: We administered HRV
      biofeedback (HRV-BF) using resonant breathing to 54 family caregivers who felt
      burdened by their nursing care responsibilities. RESULTS: Among the self-care
      group, 92.6% of participants completed the study in their homes; 28 days after
      intervention initiation, the resonant breathing implementation rate at home was
      86.1%. There was an interaction between time course and grouping in our HRV
      comparisons: the change rate in the home self-care group was higher during HRV-BF
      than before HRV-BF. CONCLUSIONS: Because family caregivers in our study learned
      to quickly administer resonant breathing using a portable device at home,
      resonant breathing improved rapidly, along with autonomic nerve function and
      quality of life.

PMID- 30183464
TI  - The Effort in Exploration of a Definitive Predictive Factor From PD-1/PD-L1
      Blockade in Advanced or Metastatic Urothelial Cancer.

PMID- 30183465
TI  - Reply to S. Zhang et al.

PMID- 30183466
TI  - Clinically Localized Prostate Cancer: ASCO Clinical Practice Guideline
      Endorsement of an American Urological Association/American Society for Radiation
      Oncology/Society of Urologic Oncology Guideline.
AB  - Purpose In April 2017, the American Urological Association, American Society for
      Radiation Oncology, and Society of Urologic Oncology released a joint evidence
      based practice guideline on clinically localized prostate cancer. The American
      Society of Clinical Oncology (ASCO) has a policy and set of procedures for
      endorsing clinical practice guidelines that have been developed by other
      professional organizations. Methods The Clinically Localized Prostate Cancer
      guideline was reviewed for developmental rigor by methodologists. An ASCO Expert
      Panel then reviewed the content and the recommendations. Results The ASCO Expert
      Panel determined that the recommendations from the Clinically Localized Prostate
      Cancer guideline were clear, thorough, and based upon the most relevant
      scientific evidence. ASCO endorsed the Clinically Localized Prostate Cancer
      guideline except for two recommendations on cryosurgery. The two recommendations
      covering cryosurgery were not endorsed because the panel found that there is
      insufficient evidence to support the use of cryotherapy in this setting.
      Recommendations The ASCO Expert Panel endorsed all but two of the original
      guideline recommendations as written and offered a series of discussion points to
      guide practice.

PMID- 30183467
TI  - End-of-Life Care Intensity in Patients Undergoing Allogeneic Hematopoietic Cell
      Transplantation: A Population-Level Analysis.
AB  - Purpose Intensity of end-of-life care receives much attention in oncology because
      of concerns that high-intensity care is inconsistent with patient goals, leads to
      worse caregiver outcomes, and is expensive. Little is known about such care in
      those undergoing allogeneic hematopoietic cell transplantation (HCT), a
      population at high risk for morbidity and mortality. Patients and Methods We
      conducted a population-based analysis of patients who died between 2000 and 2013,
      within 1 year of undergoing an inpatient allogeneic HCT using California
      administrative data. Previously validated markers of intensity were examined and
      included: hospital death, intensive care unit (ICU) admission, and procedures
      such as intubation and cardiopulmonary resuscitation at end of life.
      Multivariable logistic regression models determined clinical and sociodemographic
      factors associated with: hospital death, a medically intense intervention (ICU
      admission, cardiopulmonary resuscitation, hemodialysis, intubation), and >= two
      intensity markers. Results Of the 2,135 patients in the study population, 377
      were pediatric patients (age <= 21 years), 461 were young adults (age 22 to 39
      years), and 1,297 were adults (age >= 40 years). The most common intensity
      markers were: hospital death (83%), ICU admission (49%), and intubation (45%).
      Medical intensity varied according to age, underlying diagnosis, and presence of
      comorbidities at time of HCT. Patients with higher-intensity end-of-life care
      included patients age 15 to 21 years and 30 to 59 years, patients with acute
      lymphoblastic leukemia, and those with comorbidities at time of HCT. Conclusion
      Patients dying within 1 year of inpatient allogeneic HCT are receiving medically
      intense end-of-life care with variations related to age, underlying diagnosis,
      and presence of comorbidities at time of HCT. Future studies need to determine if
      these patterns are consistent with patient and family goals.

PMID- 30183468
TI  - Automated Detection of Conversational Pauses from Audio Recordings of Serious
      Illness Conversations in Natural Hospital Settings.
AB  - OBJECTIVE: Automating conversation analysis in the natural clinical setting is
      essential to scale serious illness communication research to samples that are
      large enough for traditional epidemiological studies. Our objective is to
      automate the identification of pauses in conversations because these are
      important linguistic targets for evaluating dynamics of speaker involvement and
      turn-taking, listening and human connection, or distraction and disengagement.
      DESIGN: We used 354 audio recordings of serious illness conversations from the
      multisite Palliative Care Communication Research Initiative cohort study.
      SETTING/SUBJECTS: Hospitalized people with advanced cancer seen by the palliative
      care team. MEASUREMENTS: We developed a Random Forest machine learning (ML)
      algorithm to detect Conversational Pauses of two seconds or longer. We triple
      coded 261 minutes of audio with human coders to establish a gold standard for
      evaluating ML performance characteristics. RESULTS: ML automatically identified
      Conversational Pauses with a sensitivity of 90.5 and a specificity of 94.5.
      CONCLUSIONS: ML is a valid method for automatically identifying Conversational
      Pauses in the natural acoustic setting of inpatient serious illness
      conversations.

PMID- 30183469
TI  - Opioid Analgesics Prescription to End-of-Life Cancer Patients: Characteristics,
      Attitudes, and Practices of French General Practitioners.
AB  - BACKGROUND: Pain management, especially at the end of life, varies depending on
      the prescriber's characteristics and attitudes. Little is known about the
      practices of general practitioners (GPs) regarding end-of-life management for
      patients with cancer. OBJECTIVES: To provide an overview of the characteristics
      associated with GPs' attitudes and practices regarding opioids prescribing and to
      explore GPs' perceived role and difficulties in managing end-of-life care for
      patients with cancer. DESIGN: A cross-sectional study (December 2015 to March
      2016). Subjects and Analyses: Data were collected from a representative sample of
      376 GPs in southeastern France recruited to participate in a survey on medical
      practices and opinions regarding cancer patient management. Descriptive analyses
      and multivariate logistic regressions were conducted to study the
      characteristics, attitudes, and practices associated with GPs' opioids
      prescribing attitudes. RESULTS: Almost 97% of GPs stated that they prescribe
      opioids to end-of-life cancer patients. Among these, 77% said that they prescribe
      opioids on their own initiative, while 23% declared doing so in coordination with
      a specialist team. Female GPs, GPs working in solo practices, and GPs reporting
      more difficulties in managing end-of-life cancer patients were significantly less
      likely to prescribe opioids on their own initiative. CONCLUSION: Our results
      suggest that GPs' characteristics and practices influence the prescribing
      attitudes at the end of life. Given the dearth of studies on this topic, further
      research is recommended to better understand the impact of GPs' characteristics
      on their prescriptive attitudes. The possible interactions between patients' and
      physicians' characteristics-in particular gender-should also be investigated.

PMID- 30183470
TI  - Superior Colliculus Signals Decisions Rather Than Confidence: Analysis of Single
      Neurons.
AB  - Recent findings indicate that monkeys can report their confidence in perceptual
      decisions, and that this information is encoded in neurons involved in making
      decisions, including the lateral intraparietal area (LIP) and the supplementary
      eye field (SEF). A key issue to consider when studying confidence is that
      decision accuracy often correlates with confidence. Expanding on work performed
      in humans, we designed a novel task for monkeys that dissociates perceptual
      information leading to decisions from perceptual information leading to
      confidence reports. Using this task, we recently showed that decoded ensemble
      activity recorded from the superior colliculus (SC) reflected decisions rather
      than confidence reports. However, our previous population analysis collapsed over
      multiple SC neuronal types and therefore left open the possibility that first,
      individual discharge rates might encode information related to confidence and
      second, that different neuronal cell types within the SC might signal decision
      confidence independently of decision accuracy. We found that when decision
      accuracy and decision confidence co-varied, modulation occurred primarily in
      buildup neurons. However, isolating decision confidence from decision accuracy
      uncovered that only a few, primarily buildup neurons showed signals correlating
      uniquely with decision confidence, and the effect sizes were very small. Based on
      this work and our previous work using decoding methods, we conclude that neuronal
      signals for decision confidence, independent of decision accuracy, are unlikely
      to exist at the level of single or populations of neurons in the SC. Together,
      these results call into question normative models of confidence based on the
      optimal read-out of decision signals.

PMID- 30183472
TI  - Visuomotor feedback gains are modulated by gaze position.
AB  - During goal-directed reaching, people typically direct their gaze to the target
      before the start of the hand movement and maintain fixation until the hand
      arrives. This gaze strategy improves reach accuracy in two ways: It enables the
      use of central vision at the end of movement and it allows the use of
      extraretinal information in guiding the hand to the target. Here we tested
      whether fixating the reach target further facilitates reach accuracy by
      optimizing the use of peripheral vision in detecting, and rapidly responding to,
      reach errors during the ongoing movement. We examined automatic visuomotor
      corrections in response to displacements of the cursor representing the hand
      position as a function of gaze fixation location during unimanual goal-directed
      reaching. Eight fixation targets were positioned either in line with, or at
      different angles relative to, the straight-ahead movement direction (manipulation
      of fixation angle), and at different distances from the location of the visual
      perturbation (manipulation of fixation distance). We found that corrections were
      fastest and strongest when gaze was directed at the reach target, compared to
      when gaze was directed to a different location in the workspace. We found that
      the gain of the visuomotor response was strongly affected by fixation angle, and
      to a smaller extent by fixation distance, with lower gains as the angle or
      distance increased. We submit that fixating the reach target improves reach
      accuracy by facilitating rapid visuomotor responses to reach errors viewed in
      peripheral vision.

PMID- 30183471
TI  - Movement and perception recalibrate differently across multiple days of locomotor
      learning.
AB  - Learning a new movement through error-based adaptation leads to recalibration of
      movement and altered perception of that movement. Although presumed to be closely
      related, the relationship between adaptation-based motor and perceptual changes
      is not well understood. Here we investigated the changes in motor behavior and
      leg speed perception over 5 days of split-belt treadmill adaptation. We
      specifically wanted to know if changes in the perceptual domain would demonstrate
      savings-like behavior (i.e., less recalibration with more practice) and if these
      changes would parallel the savings observed in the motor domain. We found that
      the recalibration of leg speed perception decreased across days of training,
      indicating savings-like behavior in this domain. However, we observed that the
      magnitude of savings across days was different between motor and perceptual
      domains. These findings suggest a degree of independence between the motor and
      perceptual processes that occur with locomotor adaptation. NEW & NOTEWORTHY Error
      based adaptation learning drives changes in movement and perception of movement.
      Are these changes across domains linked or simply coincidental? Here, we studied
      changes in movement and perception across 5 days of repeated locomotor
      adaptation. Savings-like behavior in the motor and perceptual domains developed
      with different magnitudes and over different timescales, leading us to conclude
      that motor and perceptual processes operate at least somewhat independently
      during locomotor adaptation.

PMID- 30183473
TI  - Adverse Childhood Experiences and Mental and Behavioral Health Conditions During
      Pregnancy: The Role of Resilience.
AB  - INTRODUCTION: Little is known about how exposure to adverse childhood experiences
      (ACEs) and protective factors, such as resilience, influence prenatal mental and
      behavioral health. This study examined associations between exposure to ACEs and
      mental and behavioral health during pregnancy overall and among women with high
      versus low levels of resilience. MATERIALS AND METHODS: Women in two Kaiser
      Permanente Northern California medical centers were screened for ACEs and
      resilience during prenatal care (~14-23 weeks of gestation; N = 355).
      Multivariable logistic regression analyses examined associations between ACEs and
      prenatal mental and behavioral health conditions overall and for women with low
      (<=32) versus high (>32) resilience on the 10-item Connor-Davidson Resilience
      Scale. RESULTS: Overall, 54% of women reported 0 ACEs, 28% 1-2 ACEs, and 18% 3+
      ACEs. Relative to women with 0 ACEs, those with 1-2 ACEs had higher odds of an
      anxiety or depressive disorder and intimate partner violence (IPV) (odds ratios
      [ORs] 2.42-3.12, p < 0.05), and those with 3+ ACEs had higher odds of an anxiety
      or depressive disorder, depression symptoms, and IPV (ORs 3.08-4.71, p < 0.05).
      In stratified analyses by high (56%) and low (44%) resilience, having one or more
      ACEs (vs. 0 ACEs) was only associated with worse mental and behavioral health in
      women with low resilience. CONCLUSIONS: ACEs predicted mental and behavioral
      health conditions among pregnant women, and associations were the strongest among
      women with low levels of current resilience. Longitudinal research is needed to
      understand the causal mechanisms underlying these associations.

PMID- 30183474
TI  - The Time Is Now: Reducing Racial Risk of Hypertension with Postpregnancy Follow
      Up.

PMID- 30183475
TI  - Enhancing the efficacy of glycolytic blockade in cancer cells via RAD51
      inhibition.
AB  - : Targeting the early steps of the glycolysis pathway in cancers is a well
      established therapeutic strategy; however, the doses required to elicit a
      therapeutic effect on the cancer can be toxic to the patient. Consequently,
      numerous preclinical and clinical studies have combined glycolytic blockade with
      other therapies. However, most of these other therapies do not specifically
      target cancer cells, and thus adversely affect normal tissue. Here we first show
      that a diverse number of cancer models - spontaneous, patient-derived xenografted
      tumor samples, and xenografted human cancer cells - can be efficiently targeted
      by 2-deoxy-D-Glucose (2DG), a well-known glycolytic inhibitor. Next, we tested
      the cancer-cell specificity of a therapeutic compound using the MEC1 cell line, a
      chronic lymphocytic leukemia (CLL) cell line that expresses activation induced
      cytidine deaminase (AID). We show that MEC1 cells, are susceptible to 4,4'
      Diisothiocyano-2,2'-stilbenedisulfonic acid (DIDS), a specific RAD51 inhibitor.
      We then combine 2DG and DIDS, each at a lower dose and demonstrate that this
      combination is more efficacious than fludarabine, the current standard- of- care
      treatment for CLL. This suggests that the therapeutic blockade of glycolysis
      together with the therapeutic inhibition of RAD51-dependent homologous
      recombination can be a potentially beneficial combination for targeting AID
      positive cancer cells with minimal adverse effects on normal tissue.
      IMPLICATIONS: Combination therapy targeting glycolysis and specific RAD51
      function shows increased efficacy as compared to standard of care treatments in
      leukemias.

PMID- 30183477
TI  - Integrating Sexuality and Gender Identity into the Reproductive Life Plan.
AB  - The reproductive life plan tool is severely underutilized, yet has proven to be
      successful in improving preconception health. The majority of resources utilizing
      a reproductive life plan tool are tailored to heterosexual women. However,
      millions of individuals in the United States do not fall under that
      classification. In addition, existing reproductive life plan tools treat
      reproduction as a dichotomous decision. In reality, a reproductive life plan is
      much more complex than the decision to have, or not to have children. The
      development and incorporation into health professionals education of a
      reproductive life plan tool that is inclusive of all gender identities and
      sexualities could greatly improve preconception health, and have positive impact
      on the physical and mental health of individuals of reproductive age.

PMID- 30183476
TI  - Sodium chloride (NaCl) potentiates digoxin-induced anti-tumor activity in small
      cell lung cancer.
AB  - Small cell lung cancer (SCLC) is a malignant neuroendocrine tumor with very high
      mortality. Effective new therapy for advanced SCLC patients is urgently needed.
      By screening a FDA-approved drug library, we identified a cardiac glycoside (CG),
      namely digoxin (an inhibitor of cellular Na+/K+ ATPase pump), which was highly
      effective in inhibiting SCLC cell growth. Intriguing findings showed that NaCl
      supplement markedly enhanced the anti-tumor activities of digoxin in both in
      vitro and in vivo models of SCLC. Subsequent analysis revealed that this novel
      combination of digoxin/NaCl caused an up-regulation of intracellular Na+ and Ca2+
      levels with an induction of higher resting membrane potential of SCLC cells. We
      also found that this combination lead to morphological shrinking of SCLC cells,
      together with high levels of cytochrome C release. Lastly, our data revealed that
      NaCl supplement was able to induce the expression of ATP1A1 (a Na+/K+ ATPase
      subunit), in which contributes directly to the increased sensitivity of SCLC
      cells to digoxin. Thus, this is the first demonstration that NaCl is a potent
      supplement necessitating superior anti-cancer effects of digoxin for SCLC.
      Further, our study suggests that digoxin treatment could need to be combined with
      NaCl supplement in future clinical trial of SCLC, particularly where low Na+ is
      often present in SCLC patients.

PMID- 30183478
TI  - MicroRNA-497-5p down-regulation increases PD-L1 expression in clear cell renal
      cell carcinoma.
AB  - Recent advances in immunotherapy are raising hope to treat clear cell renal cell
      carcinoma (ccRCC) with PD-L1 inhibitors, but only a small portion of patients are
      PD-L1 positive. The heterogeneous expression pattern of PD-L1 in patient
      population suggests that PD-L1 expression is under the control of diverse
      regulatory mechanisms. Although recent studies have identified numerous novel PD
      L1 regulators, reports on microRNAs which modulate PD-L1 expression are much
      scarce. In this study, we confirmed that PD-L1 expression was up-regulated in
      ccRCC compared to paired normal tissues. Using miRDB and miRTarBase, 11 microRNAs
      were predicted to target PD-L1. After measuring the microRNA panel with TaqMan
      assays, we found that microRNA-497-5p down-regulation was associated with PD-L1
      up-regulation. In TCGA-KIRC dataset, microRNA-497-5p down-regulation was also
      associated with PD-L1 up-regulation as well as shorter survival. We further
      validated that PD-L1 was a direct target of microRNA-497-5p in two RCC cell
      lines. In addition, microRNA-497-5p inhibited cell proliferation, clone formation
      and migration, while promoted apoptosis in in-vitro assays. Our study reveals a
      novel regulatory mechanism of PD-L1 expression and the potential of miR-497-5p as
      therapeutic target and biomarker deserves further investigation.

PMID- 30183479
TI  - Borderline Personality Features Mediate the Association Between ADHD, ODD, and
      Relational and Physical Aggression in Girls.
AB  - OBJECTIVE: This study investigates borderline personality features (BPF) as a
      mediator of the association between ADHD and ODD symptoms and aggression in
      girls. METHOD: Parents of 118 girls ( Mage = 11.40 years old) with and without
      ADHD completed ratings of ADHD and ODD severity, and parents and youth provided
      ratings of physical and relational aggression. RESULTS: ADHD, ODD, and their
      subfactors were significantly correlated with BPF, and these variables were
      associated with aggression measures. BPF fully mediated the association between
      total ODD symptom severity and relational and physical aggression by parent and
      youth report. At the subfactor level, BPF fully mediated the association between
      hyperactivity/impulsivity and oppositional behavior and physical and relational
      aggression. CONCLUSION: These findings add to a growing literature showing the
      relevance of BPF as a risk factor for poor social functioning in youth and point
      to the importance of continued work examining BPF among girls with ADHD and ODD.

PMID- 30183480
TI  - High frequency ultrasound imaging as a "potential" way of evaluation modality in
      side effects of lip augmentation - case report.
AB  - Lip augmentation is a popular procedure performed by esthetic medicine doctors,
      however, it is associated with a significant number of side effects. High
      frequency ultrasound imaging helps with diagnosis of side effects.The patient was
      43-year-old healthy female, 8 months after lip augmentation.The examination
      showed a variety of delayed side effects of lip augemntation. Ultrasound imaging
      revealed an increased echogenicity of lip soft tissue, too deep filler injection,
      occlusion of the inferior labial artery.

PMID- 30183481
TI  - Non-specific effects of childhood vaccines on acute childhood morbidity among HIV
      exposed children in sub-Saharan Africa: a multilevel analysis.
AB  - We examined the roles of determining factors responsible for acute respiratory
      infections and diarrhoea among immunised human immunodeficiency virus (HIV)
      exposed children in sub-Saharan Africa. This study used demographic and health
      surveys obtained from 27 sub-Saharan African countries. The outcome variable is
      defined as symptoms of acute respiratory infections or episode of diarrhoea in
      the child of an HIV-infected mother who is vaccinated with the third dose of
      diphtheria-tetanus-pertussis containing vaccines. Multivariable logistic
      regression models were used to analyse the association between individual and
      contextual factors. The odds of developing symptoms of acute respiratory
      infections increased among those living in communities with high unemployment
      rate (Odds ratio = 1.15, 95% credible interval 1.05 to 1.26). The odds of
      developing diarrhoea increased among young mothers such that children of women
      aged 15-24 years were two times likely to develop diarrhoea compared to children
      of women aged 35-49 years (Odds ratio = 2.22, 95% credible interval 1.66 to
      2.93). Public healthcare programmes should target adolescent and young women, and
      their family members on how to prevent diarrhoea. Efforts should be made to
      identify the hotspots for development of acute respiratory diseases especially in
      communities with high rate of unemployment and to develop strategies to combat
      the diseases in such communities. Initiatives such as the integrated Global
      Action Plan for the Prevention and Control of Pneumonia and Diarrhoea which
      recommends an interrelated approach for the elimination of preventable diarrhoea
      and pneumonia deaths should be adopted.

PMID- 30183482
TI  - Diagnosis of feline pancreatitis with SNAP fPL and Spec fPL.
AB  - Objectives Pancreatitis is a frequent disease in cats for which the ante-mortem
      diagnosis remains challenging. Feline pancreatic lipase immunoreactivity (fPLI)
      has been reported to have a high sensitivity for the diagnosis of pancreatitis.
      The aim of this study was to compare the rapid in-house test SNAP fPL with the
      standard test Spec fPL and to evaluate the use of SNAP fPL to diagnose
      pancreatitis in an emergency setting. Methods fPLI of 111 cats with a clinical
      suspicion of pancreatitis was measured with both SNAP fPL and Spec fPL.
      Furthermore, clinical signs, haematological and biochemical changes, and
      abdominal ultrasound findings were recorded. Results Seventy-eight of 111 cats
      (70.3%) were tested below the cut-off level for pancreatitis with SNAP, as well
      as Spec fPL, whereas 21/111 (18.9%) were tested with values above the cut-off
      level with both tests. In 12/111 (10.8%) cats the results were discordant. The
      comparison of both tests revealed an agreement of 78/80 (97.5%) when Spec fPL was
      ?3.5 MUg/l (negative) and 18/20 (90%) when Spec fPL was ?5.4 MUg/l (positive).
      The most common clinical signs in cats with suspected pancreatitis (n = 21) were
      lethargy (95.2%), reduced appetite and vomiting (90.5% each), dehydration
      (81.0%), diarrhoea (57.1%), abdominal pain and weight loss (47.6% each).
      Hyperglycaemia and hyperbilirubinaemia (85.7% each), increased aspartate
      transaminase (76.2%) and alanine transaminase (47.6%), leucocytosis (61.9%),
      lymphopenia (57.1%), decreased sodium and chloride (57.1% each), and increased
      urea (52.4%) were the most common abnormalities in blood work. Conclusions and
      relevance Clinical signs, as well as routine blood-work changes, were non
      specific and thus proved to be insufficient to diagnose pancreatitis. The
      combination of SNAP fPL and subsequent Spec fPL, if indicated, provided the
      opportunity to rule out or to diagnose pancreatitis with a higher certainty than
      previously known test methods. This study proved SNAP fPL to be a valuable tool
      to exclude or include pancreatitis in an emergency setting.

PMID- 30183483
TI  - Prolonged effect of allergen sublingual immunotherapy to grass pollen.
AB  - BACKGROUND: The prolonged effect of allergen immunotherapy is unknown, especially
      in older patients. OBJECTIVE: The three-year effect of sublingual allergen
      specific immunotherapy (AIT) to grass pollen on elderly patients with allergic
      rhinitis was analyzed. METHODS: Thirty-eight elderly patients (63.18 +/- 3.12
      yrs.) underwent AIT to grass pollen, were monitored for three years and were
      compared to a placebo group. AIT was performed with the use of an oral Staloral
      300 SR grass extract (Stallergens Greer, London, UK) or a placebo. Symptoms and
      medication scores, represented by the average adjusted symptom score (AAdSS), the
      serum level of IgG4 to Phl p5 and the quality of life were assessed immediately
      after AIT and three years later. RESULTS: After AIT, the AAdSS was significantly
      decreased and remained lower than in the placebo group during the three years
      after AIT. Serum-specific IgG4 against Phl p5 increased during the AIT trial in
      the study group. For the three years of observation after AIT, there were no
      significant changes in specific IgG4 levels against the analyzed allergens in
      comparison to the results immediately after AIT. The quality of life, based on
      the Rhinoconjunctivitis Quality of Life Questionnaire, was significantly
      decreased in patients who received AIT, from 1.83 (95%CI: 1.45-1.96) to 0.74
      (95%CI: 0.39-1.92) (p < 0.05) to 0.82 (95%CI: 0.45- 1.04) three years after AIT.
      CONCLUSION: A prolonged positive effect after AIT to grass pollen was observed in
      elderly patients with allergic rhinitis. Further trials are needed to confirm
      this effect.

PMID- 30183484
TI  - Effective fecal microbiota transplantation for recurrent Clostridioides difficile
      infection in humans is associated with increased signalling in the bile acid
      farnesoid X receptor-fibroblast growth factor pathway.
AB  - The mechanisms of efficacy for fecal microbiota transplantation (FMT) in treating
      recurrent Clostridioides difficile infection (rCDI) remain poorly defined, with
      restored gut microbiota-bile acid interactions representing one possible
      explanation. Furthermore, the potential implications for host physiology of these
      FMT-related changes in gut bile acid metabolism are also not well explored. In
      this study, we investigated the impact of FMT for rCDI upon signalling through
      the farnesoid X receptor (FXR)-fibroblast growth factor (FGF) pathway. Herein, we
      identify that in addition to restoration of gut microbiota and bile acid
      profiles, FMT for rCDI is accompanied by a significant, sustained increase in
      circulating levels of FGF19 and reduction in FGF21. These FGF changes were
      associated with weight gain post-FMT, to a level not exceeding the pre-rCDI
      baseline. Collectively, these data support the hypothesis that the restoration of
      gut microbial communities by FMT for rCDI is associated with an upregulated FXR
      FGF pathway, and highlight the potential systemic effect of FMT.

PMID- 30183485
TI  - New modalities of allergen immunotherapy.
AB  - Allergen immunotherapy is a rapidly evolving field. Although subcutaneous
      immunotherapy has been practiced for over a hundred years, improved understanding
      of the underlying immunological mechanisms has led to the development of new,
      efficacious and better tolerated allergen-derivatives, adjuvants and encapsulated
      allergens. Diverse routes of allergen immunotherapy - oral, sublingual,
      epicutanoeus and intralymphatic - are enabling immunotherapy for anaphylactic
      food allergies and pollen-food allergy syndrome, while improving the tolerability
      and effectiveness of aeroallergen immunotherapy. The addition of Anti-IgE therapy
      decreases adverse effects of subcutaneous and oral immunotherapy.

PMID- 30183486
TI  - Oral cholera vaccines and their impact on the global burden of disease.
AB  - With one-third of nations at risk of cholera, we can expect to experience
      massive, rapidly disseminated, and prolonged cholera outbreaks such as those
      recently experienced in Yemen and Haiti. The prevention of cholera outbreaks like
      these includes the provision of potable water, sanitation, and hygiene (WASH).
      This approach has been known for generations. However, it will be many years
      before universal global access to WASH is achieved. While working toward
      universal WASH, study data has shown that licensed and WHO prequalified cholera
      vaccines are important tools for cholera prevention. Oral inactivated whole-cell
      vaccines such as Shanchol and Euvichol-plus provide well-documented direct
      benefits to vaccine recipients and to the unimmunized through herd protection.
      Manufacturers have now increased the cholera vaccine supply, and since 2013
      vaccine doses have been available for emergency and endemic control through a
      global stockpile. Advances in packaging and vaccine temperature control, reduced
      vaccine costs, the inclusion of pregnant women in vaccine campaigns, and a
      targeted approach to high incidence endemic areas are further increasing the
      usefulness of these vaccines for reducing the global cholera burden.

PMID- 30183487
TI  - Intestinal luminal putrescine is produced by collective biosynthetic pathways of
      the commensal microbiome.
AB  - The intestinal microbiome produces various metabolites that may harm or benefit
      the host. However, the production pathways of these metabolites have not been
      well characterised. The polyamines putrescine and spermidine required for
      physiological process are also produced by intestinal microbiome. The production
      and release of these polyamines by microbiome are poorly understood, though we
      have confirmed that intestinal bacteria produced putrescine from arginine. In
      this study, we characterised polyamine synthesis by analysing the collective
      metabolic functions of the intestinal microbiome. In particular, we analysed
      polyamines and their intermediates in faecal cultures, as well as the colonic
      contents of rats injected with isotope-labelled arginine through a colon
      catheter, using mass spectrometry. Isotope-labelled putrescine was detected in
      faecal cultures and colonic contents of rats injected with isotope-labelled
      arginine. Putrescine is produced through multiple pathways, and its extracellular
      intermediates are exchanged between bacterial species. Additionally, we
      demonstrated that the collective metabolic pathway depends on a complex exchange
      of metabolites released into the colonic lumen. This study demonstrates the
      existence of putrescine biosynthetic pathways based on the collective metabolic
      functions of the intestinal microbial community. Our findings provide knowledge
      to manipulate the levels of intestinal microbial products, including polyamines,
      that may modulate host health.

PMID- 30183488
TI  - Morbidity benefit conferred by childhood immunisation in relation to maternal HIV
      status: a meta-analysis of demographic and health surveys.
AB  - The study determined the prevalence of acute respiratory infections and diarrhoea
      among sub-Saharan African children. It also examined if there was any significant
      morbidity benefit conferred by three doses of diphtheria-tetanus-pertussis
      containing vaccines (DTP3) with respect to maternal HIV status. Data were
      obtained from the Demographic and Health Survey (DHS) program, United Nations
      Development Programs, World Bank and Joint United Nations Programme on HIV/AIDS.
      Pooled odds ratio (OR) and 95% confidence intervals (CI) were calculated for the
      countries. Test of heterogeneity, sensitivity analyses and meta-regression were
      also conducted. The prevalence of acute respiratory infections and diarrhoea were
      similar between the children that were vaccinated and those who were not
      vaccinated with DTP3. The pooled result shows that children who did not receive
      DTP3 were more likely to have symptoms of acute respiratory infections than
      children who had DTP3 (OR 1.09, 95% CI 1.02 to 1.17); with low heterogeneity
      across the countries. The combined result for diarrhoea shows that children who
      did not receive DTP3 were less likely to have episodes of diarrhoea than children
      who received DTP3 (OR 0.83, 95% CI 0.74 to 0.92); with substantial heterogeneity
      across the countries. There was no difference between the estimates of DTP3
      vaccinated and unvaccinated children of HIV seropositive mothers with respect to
      symptoms of acute respiratory infections or episodes of diarrhoea. Tackling
      various causes and risk factors for respiratory tract infections and diarrhoeal
      diseases should be a priority for various stakeholders in sub-Saharan Africa.

PMID- 30183489
TI  - Utility of extracellular matrix powders in tissue engineering.
AB  - Extracellular matrix (ECM) materials have had remarkable success as scaffolds in
      tissue engineering (TE) and as therapies for tissue injury whereby the ECM
      microenvironment promotes constructive remodeling and tissue regeneration. ECM
      powder and solubilized derivatives thereof have novel applications in TE and RM
      afforded by the capacity of these constructs to be dynamically modulated. The
      powder form allows for effective incorporation and penetration of reagents;
      hence, ECM powder is an efficacious platform for 3D cell culture and vehicle for
      small molecule delivery. ECM powder offers minimally invasive therapy for tissue
      injury and successfully treatment for wounds refractory to first-line therapies.
      Comminution of ECM and fabrication of powder-derived constructs, however, may
      compromise the biological integrity of the ECM. The current lack of optimized
      fabrication protocols prevents a more extensive and effective clinical
      application of ECM powders. Further study on methods of ECM powder fabrication
      and modification is needed.

PMID- 30183490
TI  - Prospective randomized open-label comparative study of immunogenicity after
      subunit and polymeric subunit influenza vaccines administration among mothers and
      infants.
AB  - Pregnant women are risk group for influenza infection. Results of new subunit
      vaccines application have not been studied enough. Prospective, randomized, open
      label comparative study of subunit (Agrippal) and polymeric subunit (Grippol
      plus) vaccines. 42 pairs of mothers-infants were participated in the study.
      Protective antibodies (>= 1:40) to different influenza strains were registered on
      day 1 after the birth on the same level as 53% of cases in pairs mothers-infants
      after immune adjuvant polymeric subunit and subunit vaccines administration.
      There were the same level of protective antibodies (AB) among mothers after 3
      month, but transplacental antibodies decreased among infants and registered in
      the 13-22% cases of Grippol plus group and 31-43% cases in Agrippal S1 group. AB
      titre to influenza virus A/H1N1/pdm09 and A/H3N2/in pairs mothers-infants were
      the same in both groups in first days after birth, but AB levels to B strain were
      lower among infants without regard to vaccine. There is no difference in AB
      titres among infants of both groups at 3 month of age, but their levels were
      twice lower versus initial data. An immune adjuvant polymeric subunit as well as
      subunit vaccines application in pregnant women forms protective AB in pairs
      mothers-infants.

PMID- 30183493
TI  - Response to Christison et al. (DOI: 10.1089/neu.2017.5413): Intermittent
      Catheterization: The Devil Is in the Details.

PMID- 30183492
TI  - A synthetic anti-Frizzled antibody engineered for broadened specificity exhibits
      enhanced anti-tumor properties.
AB  - Secreted Wnt ligands play a major role in the development and progression of many
      cancers by modulating signaling through cell-surface Frizzled receptors (FZDs).
      In order to achieve maximal effect on Wnt signaling by targeting the cell
      surface, we developed a synthetic antibody targeting six of the 10 human FZDs. We
      first identified an anti-FZD antagonist antibody (F2) with a specificity profile
      matching that of OMP-18R5, a monoclonal antibody that inhibits growth of many
      cancers by targeting FZD7, FZD1, FZD2, FZD5 and FZD8. We then used combinatorial
      antibody engineering by phage display to develop a variant antibody F2.A with
      specificity broadened to include FZD4. We confirmed that F2.A blocked binding of
      Wnt ligands, but not binding of Norrin, a ligand that also activates FZD4.
      Importantly, F2.A proved to be much more efficacious than either OMP-18R5 or F2
      in inhibiting the growth of multiple RNF43-mutant pancreatic ductal
      adenocarcinoma cell lines, including patient-derived cells.

PMID- 30183491
TI  - Preclinical pharmacokinetics and pharmacodynamics of DCLL9718A: An antibody-drug
      conjugate for the treatment of acute myeloid leukemia.
AB  - Few treatment options are available for acute myeloid leukemia (AML) patients.
      DCLL9718A is an antibody-drug conjugate that targets C-type lectin-like molecule
      1 (CLL-1). This receptor is prevalent on monocytes, neutrophils, and AML blast
      cells, and unlike CD33, is not expressed on hematopoietic stem cells, thus
      providing possible hematopoietic recovery. DCLL9718A comprises an anti-CLL-1 IgG1
      antibody (MCLL0517A) linked to a pyrrolobenzodiazepine (PBD) dimer payload, via a
      cleavable disulfide-labile linker. Here, we characterize the in vitro and in vivo
      stability, the pharmacokinetics (PK) and pharmacodynamics (PD) of DCLL9718A and
      MCLL0517A in rodents and cynomolgus monkeys. Three key PK analytes were measured
      in these studies: total antibody, antibody-conjugated PBD dimer and unconjugated
      PBD dimer. In vitro, DCLL9718A, was stable with most (> 80%) of the PBD dimer
      payload remaining conjugated to the antibody over 96 hours. This was
      recapitulated in vivo with antibody-conjugated PBD dimer clearance estimates
      similar to DCLL9718A total antibody clearance. Both DCLL9718A and MCLL0517A
      showed linear PK in the non-binding rodent species, and non-linear PK in
      cynomolgus monkeys, a binding species. The PK data indicated minimal impact of
      conjugation on the disposition of DCLL9718A total antibody. Finally, in
      cynomolgus monkey, MCLL0517A showed target engagement at all doses tested (0.5
      and 20 mg/kg) as measured by receptor occupancy, and DCLL9718A (at doses of 0.05,
      0.1 and 0.2 mg/kg) showed strong PD activity as evidenced by notable reduction in
      monocytes and neutrophils.

PMID- 30183494
TI  - Hypolipidemic, Antioxidant, and Antiapoptotic Effects of Polysaccharides
      Extracted from Reishi Mushroom, Ganoderma lucidum (Leysser: Fr) Karst, in Mice
      Fed a High-Fat Diet.
AB  - The mechanisms underlying the effect of Ganoderma lucidum (Reishi mushroom)
      polysaccharides (GLP) on obesity are not clear. In this study, GLP were found to
      attenuate the oleic acid-induced cell viability loss and apoptosis dose
      dependently in splenic lymphocytes in vitro. The effects of GLP on lipid
      metabolism, oxidative stress, and apoptosis in mice fed a high-fat diet (HD) were
      determined. GLP administration (200 and 400 mg/kg bw) significantly lowered the
      body-weight increases; liver, heart, and white adipose tissues indexes; serum
      lipid accumulation; and serum and small intestine oxidative stress in mice fed a
      HD. Moreover, GLP inhibited HD-induced apoptosis by decreasing the Bax/Bcl-2
      ratio and suppressing caspase-3 activation in splenic lymphocytes. These findings
      indicate that GLP can exert hypolipidemic, antioxidant, and antiapoptotic effects
      in HD-induced obese mice.

PMID- 30183496
TI  - The effects of type 2 diabetes mellitus and its complications on physical and
      pulmonary functions: A case-control study.
AB  - AIMS: This study was planned to determine the effects of type 2 diabetes mellitus
      (DM) and its complications on physical and pulmonary functions. METHODS: A total
      of 110 individuals aged 40-65 years were included in the study, 58 with type 2 DM
      (study group) and 52 without DM (control group). Physical activity level,
      functional capacity, pulmonary function, and comorbidity levels were compared
      between the groups. RESULTS: The mean age of the individuals was 52.42 +/- 5.88
      years. Six-minute walk test distance was 507.2 +/- 51.70 m in the study group and
      532.23 +/- 50.32 m in the control group (p < 0.05, Cohen's d = 0.49). The
      pulmonary function test results of the study and control groups were determined
      as forced vital capacity (FVC) (%): 99.17 +/- 14.13 and 104.65 +/- 16.01 (p >
      0.05), forced expiratory volume in one second (FEV1) (%): 96.78 +/- 14.43 and
      99.73 +/- 15.80 (p > 0.05), and FEV1/FVC ratio: 81.97 +/- 4.62 and 80.16 +/- 5.27
      (p > 0.05), respectively. The Charlson Comorbidity Index scores of the study and
      control groups were 1.83 +/- 0.82 and 0.12 +/- 0.32 (p < 0.05). CONCLUSIONS: Type
      2 DM was associated with lower functional capacity and higher rates of comorbid
      diseases. Therefore, potential causes of these parameters should be considered in
      the rehabilitation of type 2 diabetic patients.

PMID- 30183495
TI  - Medicare Spending after 3 Years of the Medicare Shared Savings Program.
AB  - BACKGROUND: Health care providers who participate as an accountable care
      organization (ACO) in the voluntary Medicare Shared Savings Program (MSSP) have
      incentives to lower spending for Medicare patients while achieving high
      performance on a set of quality measures. Little is known about the extent to
      which early savings achieved by ACOs in the program have grown and been
      replicated by ACOs that entered the program in later years. ACOs that are
      physician groups have stronger incentives to lower spending than hospital
      integrated ACOs. METHODS: Using fee-for-service Medicare claims from 2009 through
      2015, we performed difference-in-differences analyses to compare changes in
      Medicare spending for patients in ACOs before and after entry into the MSSP with
      concurrent changes in spending for local patients served by providers not
      participating in the MSSP (control group). We estimated differential changes
      (i.e., the between-group difference in the change from the pre-entry period)
      separately for hospital-integrated ACOs and physician-group ACOs that entered the
      MSSP in 2012, 2013, or 2014. RESULTS: MSSP participation was associated with
      differential spending reductions in physician-group ACOs. These reductions grew
      with longer participation in the program and were significantly greater than the
      reductions in hospital-integrated ACOs. By 2015, the mean differential change in
      per-patient Medicare spending was -$474 (-4.9% of the pre-entry mean, P<0.001)
      for physician-group ACOs that entered in 2012, -$342 (-3.5% of the pre-entry
      mean, P<0.001) for those that entered in 2013, and -$156 (-1.6% of the pre-entry
      mean, P=0.009) for those that entered in 2014. The corresponding differential
      changes for hospital-integrated ACOs were -$169 (P=0.005), -$18 (P=0.78), and $88
      (P=0.14), which were significantly lower than for physician-group ACOs (P<0.001).
      Spending reductions in physician-group ACOs constituted a net savings to Medicare
      of $256.4 million in 2015, whereas spending reductions in hospital-integrated
      ACOs were offset by bonus payments. CONCLUSIONS: After 3 years of the MSSP,
      participation in shared-savings contracts by physician groups was associated with
      savings for Medicare that grew over the study period, whereas hospital-integrated
      ACOs did not produce savings (on average) during the same period. (Funded by the
      National Institute on Aging.).

PMID- 30183497
TI  - Lower-limb muscle strength, static and dynamic postural stabilities, risk of
      falling and fear of falling in polio survivors and healthy subjects.
AB  - INTRODUCTION: This study investigated the association between preserved lower
      limb muscle strength, dynamic and static postural stability, risk of falling, and
      fear of falling in polio survivors. We also investigated whether these clinical
      features differ between polio survivors and healthy controls. METHODS: This quasi
      experimental study enrolled 16 polio survivors (13 underwent a complete-case
      analysis) and 12 age- and sex-matched healthy controls. Participants were
      assessed by the manual muscle test, Berg Balance Scale, force platform
      posturography, and Falls Efficacy Scale. Between-group mean differences with
      confidence intervals (MD, CI 95%) and Spearman's rho are reported. RESULTS:
      Compared to healthy controls, polio survivors presented reduced muscle strength
      (MD = -13, CI 95% -16 to -9 points), lower dynamic postural stability (MD = -14,
      CI 95% -19 to -8 points), and increased fear of falling (MD = 14, CI 95% 10-18
      points) (all P < 0.001). In polio survivors, lower-limb muscle strength was
      correlated with dynamic (rho = 0.760) and static postural stability (rho = 0.738
      0.351), risk of falling (rho = -0.746), and fear of falling (rho = -0.432).
      Dynamic postural stability was correlated with risk of falling (rho = -0.841),
      fear of falling (rho = -0.277), and static postural stability (rho = -0.869 to 
      0.435; rho = -0.361 to -0.200, respectively). Risk and fear of falling were also
      correlated (rho = 0.464). DISCUSSION: Polio survivors exhibited impaired dynamic
      postural stability but preserved static stability and increased risk of falling
      and fear of falling. Preserved lower-limb muscle strength, postural stability,
      fear of falling, and risk of falling are associated clinical features in this
      population.

PMID- 30183498
TI  - Self-Reported Physical and Mental Health of Gender Nonconforming Transgender
      Adults in the United States.
AB  - PURPOSE: This study compares the health status of gender nonconforming
      transgender adults with gender-binary transgender peers (i.e., transgender men
      and transgender women). METHODS: We performed a retrospective analysis of the
      2014-2016 Behavioral Risk Factor Surveillance System. RESULTS: After adjustment
      for sociodemographic characteristics, proxies for healthcare access, health
      conditions, and health behaviors, gender nonconforming transgender adults were at
      increased odds, compared with gender-binary transgender peers, of self-reported
      poor or fair health and self-reported limitation in any way in any activities
      because of physical, mental, or emotional problems. CONCLUSIONS: Gender
      nonconforming transgender adults experienced worse self-reported health
      disparities than gender-binary transgender peers.

PMID- 30183499
TI  - Obesity, Visceral Fat, and Hypertension-Related Complications.
AB  - BACKGROUND: Hypertension and obesity are very common and complex cardiovascular
      (CV) risk factors. Our aim was to provide a comprehensive assessment of
      associations between visceral fat depots and vascular or cardiac complications of
      hypertension. METHODS: All the consecutive patients (age: 45-80 years old)
      scheduled for elective coronary angiography in the Department of Cardiology were
      screened, and 400 patients were included into the study group. All the patients
      had a comprehensive clinical assessment focused on hypertension and obesity, risk
      factors, fat depots, and several hypertension-related vascular or cardiac
      complications. RESULTS: The study group (n = 400; F/M: 140/260; age: 61 +/- 7
      years) included patients with hypertension (n = 354; 88.5%) and normal blood
      pressure (n = 46; 11.5%) and individuals with obesity (n = 192; 48%), diabetes (n
      = 139; 35%), metabolic syndrome (n = 240; 60%), and coronary artery disease (n =
      286; 71%). Patients with higher degrees of hypertension (grade 3 vs. 2 vs. 1)
      showed increased body mass index (BMI) and waist circumference and ultrasound
      indexes of perivascular, epicardial, and abdominal visceral fat with no
      differences in age, waist-hip ratio, and subcutaneous fat. Both visceral fat
      depots: perivascular fat (carotid extra-media thickness) and abdominal visceral
      fat (intra-abdominal thickness) assessed as single measures and ratios were
      significantly increased in hypertensive patients with high versus low global CV
      risk in a hypertension-focused risk model (differences more pronounced in
      patients <=60 years old). Visceral fat parameters were not independent, but
      rather additive to general obesity (BMI), except for visceral abdominal fat
      depot. CONCLUSIONS: Visceral abdominal and perivascular fat depots assessed as
      ultrasound indexes are associated with complications of hypertension and CV risk
      indicators, especially in patients with a mild-to-moderate hypertension and in
      younger patients.

PMID- 30183500
TI  - Detection of Glycemia and Osmolarity Changes Using Eye Examinations.
AB  - BACKGROUND: Glycated hemoglobin (HbA1c) is an index of the average blood glucose
      level over the preceding 2-3 months. In experimental studies, the lens responded
      to changes in osmolarity by forming vacuoles. By observing the vacuoles of the
      lens during eye examination, can we detect changes in osmolarity and glycemia
      over the last 6 months through HbA1c levels? METHODS: In total, 400 patients
      (mean age, 67.7 +/- 9.8 years), including those with diabetes mellitus,
      hypertension, and heart failure, were included in the study. The control group
      contained 70 patients matched in terms of age and sex and who had no prior
      disease (mean age, 67.8 +/- 9.4 years). Monthly Na, glucose, and blood urea
      nitrogen values were used to calculate changes in osmolarity over 6 months. HbA1c
      values were also recorded. Biomicroscopy was used to evaluate lens vacuolation;
      all vacuoles were digitally photographed and converted to ImageJ format. RESULTS:
      The sensitivity and specificity of using large vacuoles to detect HbA1c >=10%
      were 88.0% (95% confidence interval [CI]: 68.8-97.4) and 82.6% (95% CI: 74.1
      89.2), respectively. The sensitivity and specificity of detecting a 10 mOsm/kg
      change in osmolarity were 61% (95% CI: 48.9-72.4) and 94.5% (95% CI: 91.5-96.7),
      respectively. CONCLUSIONS: Lens vacuoles, which can be observed with a simple and
      quick examination, can be used to detect HbA1c levels and osmolarity changes over
      the last 6 months. Because of their relationship to the severity of retinopathy,
      vacuoles can also be used as a weak control indicator.

PMID- 30183501
TI  - An optimized and validated 384-well plate assay to test platelet function in a
      high-throughput screening format.
AB  - Despite significant advances in the treatment of cardiovascular diseases,
      antiplatelet therapies are still associated with a high risk of hemorrhage. In
      order to develop new drugs, methods to measure platelet function must be adapted
      for the high-throughput screening (HTS) format. Currently, all assays capable of
      assessing platelet function are either expensive, complex, or not validated,
      which makes them unsuitable for drug discovery. Here, we propose a simple, low
      cost, and high-throughput-compatible platelet function assay, validated for the
      384-well plate. In the proposed assay, agonist-induced platelet activity was
      assessed by three different methods: (i) measurement of light absorbance, which
      decreases with platelet aggregation; (ii) luminescence measurement, based on ATP
      release from activated platelets and luciferin-luciferase reaction; and (iii)
      automated bright-field microscopy of the wells and further quantification of
      platelet image area, described here for the first time. Brightfield imaging
      results were validated by demonstrating the similarity of dose-response curves
      obtained with absorbance and luminescence measurements after stimulating
      platelets, pre-incubated with prostaglandin E1 or tirofiban, and demonstrating
      the similarity of dose-response curves obtained with agonists. Assay quality was
      confirmed using the Z'-factor, a statistical parameter used to validate the
      robustness and suitability of an HTS assay. The results showed that, under high
      rotations per minute (1200 RPM), an acceptable Z'-factor score is reached for
      absorbance measurements (Z'-factor - 0.58) and automated brightfield imaging (Z'
      factor - 0.52), without the need of replicates, while triplicates must be used to
      achieve an acceptable Z'-factor score (0.54) for luminescence measurements. Using
      low platelet concentration (4 * 104/MUl - 10 MUl), the brightfield imaging test
      was further validated using washed platelets. Furthermore, drug screening was
      performed with compounds selected by structure-based virtual screening. Taken
      together, this study presents an optimized and validated assay for HTS to be used
      as a tool for antiplatelet drug discovery.

PMID- 30183502
TI  - Bugs in the system: bringing the human microbiome to bear in cancer
      immunotherapy.
AB  - The influence of the composition of the human microbiome on the efficacy of
      cancer directed immunotherapies, such as antibodies directed against the
      programmed cell death 1 protein (PD-1) or its ligand (PD-L1), has garnered
      increasing attention as the role of immunotherapies in the care of cancer has
      grown. Dysbiosis (altered microbiota) has recently been reported to adversely
      affect the efficacy of cancer directed immunotherapies, and correction of this
      dysbiosis has the potential to improve the efficacy of these treatments. However,
      the exact mechanisms underlying this relationship remains unknown. Current
      methods for characterizing the microbiome likely capture only a small portion of
      the highly complex interaction between the microbiome and the immune system. Here
      we discuss the recent reports of the influence of dysbiosis on cancer
      immunotherapy, methods to more fully characterize the interaction between the
      microbiome and the immune system, and methods of modulating the immune system to
      improve the efficacy of cancer immunotherapy.

PMID- 30183503
TI  - Antiobesity Effects of Short-Chain Chitosan in Diet-Induced Obese Mice.
AB  - Dietary chitosan is known for its antiobesity effects by combining with bile acid
      and lipid droplets. When the chitosan structure is broken into short chains, the
      fat-binding capacity increases. The aim of this study was to compare long-chain
      chitosan (LC) with short-chain chitosan (SC) for their antiobesity effects in
      high-fat diet (HFD)-induced obese C57BL/6J mice for 12 weeks. The body weights of
      mice in both chitosan groups were decreased, especially in the SC group compared
      with the LC group. Total white adipose tissue and visceral fat weights were also
      decreased in mice of the SC group more than those of the HFD group. Moreover, SC
      supplementation lowered plasma triglyceride (TG) and cholesterol levels, whereas
      LC only lowered plasma free fatty acid level. Fecal lipids were increased in mice
      of both LC and SC groups, and hepatic TG and cholesterol levels were decreased in
      both groups. SC lowered phosphatidate phosphohydrolase activity and elevated beta
      oxidation in the liver. Furthermore, SC decreased the expression of the hepatic
      lipid-regulating genes, including fatty acid synthase, peroxisome proliferator
      activated receptor (PPAR)gamma1, and PPARgamma2; and increased the expression of
      carnitine palmitoyl transferase 1alpha and peroxisome proliferator-activated
      receptor gamma coactivator (PGC)1alpha genes. In conclusion, we demonstrated that
      long-term supplementation of SC can ameliorate body weight and lipid levels by
      increasing lipid excretion and regulating lipid metabolism, including some enzyme
      activities and gene expression levels, in HFD-induced obese mice.

PMID- 30183504
TI  - Epithelial maturity influences EPEC-induced desmosomal alterations.
AB  - Desmosomes are junctional protein complexes that confer strong adhesive capacity
      to adjacent host cells. In a recent study, we showed that enteropathogenic
      Escherichia coli (EPEC) disrupts desmosomes, weakens cell-cell adhesion and
      perturbs barrier function of intestinal epithelial (C2BBe) cells. Desmosomal
      damage was dependent on the EPEC effector protein EspH and its inhibitory effect
      on Rho GTPases. EspH-mediated Rho inactivation resulted in retraction of keratin
      intermediate filaments and degradation of desmosomal cadherins.
      Immunofluorescence studies of EPEC-infected C2BBe cells revealed keratin
      retraction towards the nucleus coincident with significant cytoplasmic
      redistribution of the desmosomal cadherin desmoglein-2 (DSG2). In this addendum,
      we expand on how EPEC-induced keratin retraction leads to loss of DSG2 anchoring
      at the junctions, and show that maturity of the epithelial cell monolayer impacts
      the fate of desmosomes during infection.

PMID- 30183505
TI  - LITOMOSOIDES-MICROFILARIA IN SEVEN NEOTROPICAL BAT SPECIES.
AB  - Litomosoides spp. (Nematoda: Filarioidea: Onchocercidae) are of great interest
      for understanding dynamics of zoonoses because of their similarity to human
      infecting filariae (e.g., Onchocerca volvulus). We encountered Litomosoides
      microfilaria in blood samples from 7 Panamanian bat species. Species were
      identified through morphological analysis. We assessed individual traits and
      immune response of the host individuals as well as host species ecology. We found
      8 host-specific species/morphotypes of Litomosoides microfilariae in 5 bat
      species, with 5 individuals showing multiple infections. Our study includes the
      first records of Litomosoides brasiliensis in Artibeus jamaicensis and of
      Litomosoides-like and Litomosa-like microfilaria in Lophostoma silvicolum.
      Multiple binary regression analysis showed that the presence of specific
      Litomosoides species was influenced by host species, sex and reproductive status.

PMID- 30183506
TI  - Recent Developments in Understanding Barrier Mechanisms in the Developing Brain:
      Drugs and Drug Transporters in Pregnancy, Susceptibility or Protection in the
      Fetal Brain?
AB  - Efflux mechanisms situated in various brain barrier interfaces control drug entry
      into the adult brain; this review considers the effectiveness of these protective
      mechanisms in the embryo, fetus, and newborn brain. The long-standing belief that
      the blood-brain barrier is absent or immature in the fetus and newborn has led to
      many misleading statements with potential clinical implications. The immature
      brain is undoubtedly more vulnerable to damage by drugs and toxins; as is
      reviewed here, some developmentally regulated normal brain barrier mechanisms
      probably contribute to this vulnerability. We propose that the functional status
      of brain barrier efflux mechanisms should be investigated at different stages of
      brain development to provide a rational basis for the use of drugs in pregnancy
      and in newborns, especially in those prematurely born, where protection usually
      provided by the placenta is no longer present. Expected final online publication
      date for the Annual Review of Pharmacology and Toxicology Volume 59 is January 6,
      2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised
      estimates.

PMID- 30183507
TI  - Immunological Basis for Recurrent Fetal Loss and Pregnancy Complications.
AB  - Pregnancy stimulates an elaborate assortment of dynamic changes, allowing
      intimate approximation of genetically discordant maternal and fetal tissues.
      Although the cellular and molecular details about how this works remain largely
      undefined, important clues arise from evaluating how a prior pregnancy influences
      the outcome of a future pregnancy. The risk of complications is consistently
      increased when complications occurred in a prior pregnancy. Reciprocally, a prior
      successful pregnancy protects against complications in a future pregnancy. Here,
      we summarize immunological perturbations associated with fetal loss, with
      particular focus on how both harmful and protective adaptations may persist in
      mothers. Immunological aberrancy as a root cause of pregnancy complications is
      also considered, given their shared overlapping risk factors and the sustained
      requirement for averting maternal-fetal conflict throughout pregnancy.
      Understanding pregnancy-induced immunological changes may expose not only new
      therapeutic strategies for improving pregnancy outcomes but also new facets of
      how immune tolerance works, and these may be applicable to other physiological
      and pathological contexts. Expected final online publication date for the Annual
      Review of Pathology: Mechanisms of Disease Volume 14 is January 24, 2019. Please
      see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

PMID- 30183508
TI  - [Evaluation of the implementation process of family nursing in oncology].
AB  - : Evaluation of the implementation process of family nursing in oncology
      Abstract. BACKGROUND: The confrontation with a life-threatening cancer disease
      and the resulting consequences are a great burden for patients as well as for
      their family members. Family nursing based on the Calgary Model was implemented
      on a German oncological inpatient unit in order to strengthen the family's
      ability to self-help. AIM: The objectives were a) to systematically record,
      evaluate and if necessary to modify the implementation process, b) to highlight
      promoting and inhibiting factors and c) to derive recommendations for
      transferability to other oncological units. METHODS: The implementation process
      was examined by means of two group interviews with nurses, five interviews with
      other members of the treatment team, and observations of, in each case four,
      family assessments, family interviews and family-related team meetings. RESULTS:
      Family nursing could be implemented in a modified form. Genograms and ecomaps
      have become part of the admission interview. In family interviews, needs of the
      entire family were determined with the help of circular communication. Family
      related team meetings were carried out according to an adapted method of the
      reflecting team. The complete implementation of family nursing was impeded by the
      lack of professional consulting competences of the nursing staff, the system of
      nursing care delivery and lack of time. CONCLUSION: An implementation of family
      nursing in other oncological units is recommended under modified preconditions.

PMID- 30183509
TI  - Diplomats' Mystery Illness and Pulsed Radiofrequency/Microwave Radiation.
AB  - IMPORTANCE: A mystery illness striking U.S. and Canadian diplomats to Cuba (and
      now China) "has confounded the FBI, the State Department and US intelligence
      agencies" (Lederman, Weissenstein, & Lee, 2017). Sonic explanations for the so
      called health attacks have long dominated media reports, propelled by peculiar
      sounds heard and auditory symptoms experienced. Sonic mediation was justly
      rejected by experts. We assessed whether pulsed radiofrequency/microwave
      radiation (RF/MW) exposure can accommodate reported facts in diplomats, including
      unusual ones. OBSERVATIONS: (1) Noises: Many diplomats heard chirping, ringing or
      grinding noises at night during episodes reportedly triggering health problems.
      Some reported that sounds were localized with laser-like precision or said the
      sounds seemed to follow them (within the territory in which they were perceived).
      Pulsed RF/MW engenders just these apparent "sounds" via the Frey effect.
      Perceived "sounds" differ by head dimensions and pulse characteristics and can be
      perceived as located behind in or above the head. Ability to hear the "sounds"
      depends on high-frequency hearing and low ambient noise. (2) Signs/symptoms:
      Hearing loss and tinnitus are prominent in affected diplomats and in RF/MW
      affected individuals. Each of the protean symptoms that diplomats report also
      affect persons reporting symptoms from RF/MW: sleep problems, headaches, and
      cognitive problems dominate in both groups. Sensations of pressure or vibration
      figure in each. Both encompass vision, balance, and speech problems and
      nosebleeds. Brain injury and brain swelling are reported in both. (3) Mechanisms:
      Oxidative stress provides a documented mechanism of RF/MW injury compatible with
      reported signs and symptoms; sequelae of endothelial dysfunction (yielding blood
      flow compromise), membrane damage, blood-brain barrier disruption, mitochondrial
      injury, apoptosis, and autoimmune triggering afford downstream mechanisms, of
      varying persistence, that merit investigation. (4) Of note, microwaving of the
      U.S. embassy in Moscow is historically documented. CONCLUSIONS AND RELEVANCE:
      Reported facts appear consistent with RF/MW as the source of injury in diplomats
      in Cuba. Nondiplomats citing symptoms from RF/MW, often with an inciting pulsed
      RF/MW exposure, report compatible health conditions. Under the RF/MW hypothesis,
      lessons learned for diplomats and for RF/MW-affected civilians may each aid the
      other.

PMID- 30183511
TI  - Nonhuman Primates with Acute Radiation Syndrome: Results from a Global Serum
      Metabolomics Study after 7.2 Gy Total-Body Irradiation.
AB  - Threats of nuclear terrorism coupled with potential unintentional ionizing
      radiation exposures have necessitated the need for large-scale response efforts
      of such events, including high-throughput biodosimetry for medical triage. Global
      metabolomics utilizing mass spectrometry (MS) platforms has proven an ideal tool
      for generating large compound databases with relative quantification and
      structural information in a short amount of time. Determining metabolite panels
      for biodosimetry requires experimentation to evaluate the many factors associated
      with compound concentrations in biofluids after radiation exposures, including
      temporal changes, pre-existing conditions, dietary intake, partial- vs. total
      body irradiation (TBI), among others. Here, we utilize a nonhuman primate (NHP)
      model and identify metabolites perturbed in serum after 7.2 Gy TBI without
      supportive care [LD70/60, hematologic (hematopoietic) acute radiation syndrome
      (HARS) level H3] at 24, 36, 48 and 96 h compared to preirradiation samples with
      an ultra-performance liquid chromatography quadrupole time-of-flight (UPLC-QTOF)
      MS platform. Additionally, we document changes in cytokine levels. Temporal
      changes observed in serum carnitine, acylcarnitines, amino acids, lipids,
      deaminated purines and increases in pro-inflammatory cytokines indicate clear
      metabolic dysfunction after radiation exposure. Multivariate data analysis shows
      distinct separation from preirradiation groups and receiver operator
      characteristic curve analysis indicates high specificity and sensitivity based on
      area under the curve at all time points after 7.2 Gy irradiation. Finally, a
      comparison to a 6.5 Gy (LD50/60, HARS level H2) cohort after 24 h postirradiation
      revealed distinctly increased separations from the 7.2 Gy cohort based on
      multivariate data models and higher compound fold changes. These results
      highlight the utility of MS platforms to differentiate time and absorbed dose
      after a potential radiation exposure that may aid in assigning specific medical
      interventions and contribute as additional biodosimetry tools.

PMID- 30183510
TI  - Biomechanical behavior of modular acetabular cups made of poly-ether-ether
      ketone: A finite element study.
AB  - After total hip arthroplasty, stress-shielding is a potential risk factor for
      aseptic loosening of acetabular cups made of metals. This might be avoided by the
      use of acetabular cups made of implant materials with lower stiffness. The
      purpose of this numerical study was to determine whether a modular acetabular cup
      with a shell made of poly-ether-ether-ketone or poly-ether-ether-ketone
      reinforced with carbon fibers might be an alternative to conventional metallic
      shells. Therefore, the press-fit implantation of modular cups with shells made of
      different materials (Ti6Al4V, poly-ether-ether-ketone, and poly-ether-ether
      ketone reinforced with carbon fibers) and varying liner materials (ceramics and
      ultra-high-molecular-weight polyethylene) into an artificial bone cavity was
      simulated using finite element analysis. The shell material had a major impact on
      the radial shell deformation determined at the rim of the shell, ranging from
      17.9 um for titanium over 92.2 um for poly-ether-ether-ketone reinforced with
      carbon fibers up to 475.9 um for poly-ether-ether-ketone. Larger radial liner
      deformations (up to 618.4 um) occurred in combination with the shells made of
      poly-ether-ether-ketone compared to titanium and poly-ether-ether-ketone
      reinforced with carbon fibers. Hence, it can be stated that conventional poly
      ether-ether-ketone is not a suitable shell material for modular acetabular cups.
      However, the radial shell deformation can be reduced if the poly-ether-ether
      ketone reinforced with carbon fiber material is used, while deformation of
      ceramic liners is similar to the deformation in combination with titanium shells.

PMID- 30183512
TI  - The Liking Gap in Conversations: Do People Like Us More Than We Think?
AB  - Having conversations with new people is an important and rewarding part of social
      life. Yet conversations can also be intimidating and anxiety provoking, and this
      makes people wonder and worry about what their conversation partners really think
      of them. Are people accurate in their estimates? We found that following
      interactions, people systematically underestimated how much their conversation
      partners liked them and enjoyed their company, an illusion we call the liking
      gap. We observed the liking gap as strangers got acquainted in the laboratory, as
      first-year college students got to know their dorm mates, and as formerly
      unacquainted members of the general public got to know each other during a
      personal development workshop. The liking gap persisted in conversations of
      varying lengths and even lasted for several months, as college dorm mates
      developed new relationships. Our studies suggest that after people have
      conversations, they are liked more than they know.

PMID- 30183513
TI  - A peculiar condition: A history of the Jumping Frenchmen Syndrome in scientific
      and popular accounts.
AB  - In 1878, Dr. George Beard reported to other neurologists that in Maine there
      existed French-Canadian woodsmen who jumped when excited. Beard observed the
      phenomenon firsthand and his subsequent reports attracted the attention of
      Georges Gilles de la Tourette in France and other neurologists worldwide for a
      couple of decades. During the second half of the twentieth century, interest in
      the jumpers revived among neurologists, as some came forward with similar
      observations in different parts of Canada and the United States. This article
      compares and contrasts the scientific reports of the jumping syndrome with those
      of the popular press and highlights what they revealed about the perceived status
      of French-Canadian descendants.

PMID- 30183514
TI  - Death anxiety in Lebanese college students in 1998 and 2015.
AB  - The present investigation sought to explore the difference in death anxiety
      between two different samples of students who studied at the same university in
      Lebanon in 1998 and 2015. Based on the changes in the social, economic, and
      political conditions that took place over these 17 years, it is possible to
      predict the change in death anxiety during this period. The participants in the
      1998 study included 228 undergraduates, whereas the 2015 sample consisted of 292
      students. All participants responded to Templer's Death Anxiety Scale (DAS). Sex
      related differences on the DAS were statistically significant in the 1998 group
      where women obtained a higher mean than the men. The t-test was significant at
      0.001. Among women, the 2015 group obtained a significantly lower mean score than
      did their female counterparts in the 1998 group, whereas the difference between
      the two years in men was not significant. In sum, the hypothesis of the study was
      partially verified, i.e., a change in death anxiety level in some groups has
      happened as a result of the passage of time and other factors. In this case,
      death anxiety may be considered a fluid entity influenced by different
      environmental conditions.

PMID- 30183515
TI  - Self-Affirmation Effects Are Produced by School Context, Student Engagement With
      the Intervention, and Time: Lessons From a District-Wide Implementation.
AB  - Self-affirmation shows promise for reducing racial academic-achievement gaps;
      recently, however, mixed results have raised questions about the circumstances
      under which the self-affirmation intervention produces lasting benefits at scale.
      In this follow-up to the first district-wide scale-up of a self-affirmation
      intervention, we examined whether initial academic benefits in middle school
      carried over into high school, we tested for differential impacts moderated by
      school context, and we assessed the causal effects of student engagement with the
      self-affirming writing prompted by the intervention. Longitudinal results
      indicate that self-affirmation reduces the growth of the racial achievement gap
      by 50% across the high school transition ( N = 920). Additionally, impacts are
      greatest within school contexts that cued stronger identity threats for racial
      minority students, and student engagement is causally associated with benefits.
      Our results imply the potential for powerful, lasting academic impacts from self
      affirmation interventions if implemented broadly; however, these effects will
      depend on both contextual and individual factors.

PMID- 30183516
TI  - Colon cancer-derived conditioned medium induces differentiation of THP-1
      monocytes into a mixed population of M1/M2 cells.
AB  - Macrophages play an important role in the immune response and in the maintenance
      of tissue homeostasis. It is well known that many tumors recruit monocytes from
      circulation and influence their differentiation, mainly into suppressive M2-like
      subsets. Since there are contradictory data concerning the importance of
      macrophages for colon cancer progression, we used in our experiments four colon
      cancer cell lines representing different stages of tumor development (HT29,
      LS180, SW948, SW620). An acute monocytic leukemia cell line THP-1 was used as a
      human model of monocytes. Our work revealed that conditioned medium from the
      tumor cell lines induced activation and differentiation of THP-1 cells. The
      changes involved increased expression of CD68, a macrophage differentiation
      marker. Moreover, we also observed increased expression of CD206 and CD163, which
      are widely considered as markers of tumor-associated macrophages. The tumor
      derived conditioned medium decreased the proliferation of THP-1 cells and blocked
      their cell cycle at the G1 stage. The tumor-conditioned medium also upregulated
      the production of several cytokines and chemokines characteristic of both M1 and
      M2 subsets and induced the expression of important pro-angiogenic factors,
      vascular endothelial growth factor, and matrix metalloproteinase-9 in THP-1
      cells. Moreover, the tumor-conditioned medium induced the expression of galectin
      3, which is implicated in malignant transformation, and indoleamine 2,3
      dioxygenase, that is, a key enzyme of the kynurenine pathway. Our data suggest
      that tumor cells can actively influence the phenotype of monocytes and switch
      their differentiation into a population of non-adherent mixed M1 and M2 cells.
      These preliminary studies suggest that colon cancer cells produce soluble factors
      that influence monocyte differentiation, most probably into suppressive subsets.
      These data provide a better understanding of the influence of colon cancer on
      polarization of monocytes.

PMID- 30183517
TI  - Palbociclib augments Neratinib killing of tumor cells that is further enhanced by
      HDAC inhibition.
AB  - Cancers expressing mutant RAS are associated with a weaker response to
      chemotherapy and a shorter overall patient survival. We have demonstrated that
      the irreversible inhibitor of ERBB1/2/4, neratinib, inhibits ERBB1/2/4 and causes
      their internalization and autolysosomal degradation. Fellow-traveler membrane
      proteins with RTKs, including mutant K-/N-RAS, were also degraded. We discovered
      that the CDK4/6 inhibitor palbociclib increased autophagosome and then
      autolysosome levels in a time dependent fashion, did not reduce mTOR activity,
      and interacted with temsirolimus to kill. Neratinib and palbociclib interacted in
      a greater than additive manner to increase autophagosome and then autolysosome
      levels in a time dependent fashion, and to cause tumor cell killing. Killing
      required the expression of ATM and AMPKalpha, Beclin1 and ATG5, BAX and BAK and
      of AIF, but not of caspase 9. In some cells over-expression of BCL-XL was
      protective whereas in others it was ineffective. The lethality of [neratinib +
      palbociclib] was modestly enhanced by the PDE5 inhibitor sildenafil and strongly
      enhanced by the HDAC inhibitor sodium valproate. This was associated with K-RAS
      degradation and a greater than additive increase in autophagosome and
      autolysosome levels. Killing by the three-drug combination required ATM and
      AMPKalpha, and, to a greater extent, Beclin1 and ATG5. In vivo, [valproate +
      palbociclib] and [neratinib + valproate + palbociclib] interacted to suppress the
      growth of a carboplatin/paclitaxel resistant PDX ovarian tumors that express a
      mutant N-RAS. Our data support performing a future three-drug trial with these
      agents.

PMID- 30183518
TI  - Post-Operative Infections: Trends in Distribution, Risk Factors, and Clinical and
      Economic Burdens.
AB  - BACKGROUND: Post-operative infection (POI) is a serious complication in all
      surgical disciplines and can derail a patient's treatment and recovery course. In
      this analysis, we examine national trends, risk factors, and costs associated
      with POI. METHODS: Using the Nationwide Inpatient Sample (NIS) for the years
      available for data analysis at the time of this study (2003-2010), we performed a
      cross-sectional study of adult (>=18 years) inpatients with POI and designated
      Clinical Classification Software (CCS) procedural class codes for the operations
      performed. A comparison group was selected randomly from patients with the same
      CCS codes who underwent the same procedures but did not experience POI. As the
      NIS represents 20% of U.S. hospital admissions, excess cost and stay were
      calculated on the basis of the average difference between cost and duration of
      stay for POI cases and the cost and duration of stay for the comparison group,
      then extrapolated to estimate the national burden for the remaining 80% of stays
      nationwide. RESULTS: Sample admissions included 139,652 cases of POI and 941,670
      comparison subjects. The POIs were most common in procedures involving the
      digestive tract (46.5%), cardiovascular system (16.3%), or musculoskeletal system
      (11.2%). Older age, male gender, high Charlson Comorbidity Index Score (CCIS),
      and teaching, urban, or large hospitals were independent risk factors for POI in
      the multivariable model (p < 0.05). A POI was associated with a higher risk of
      death (odds ratio 2.93; 95% confidence interval 2.82-3.04, p < 0.001).
      Nationally, we estimate that POI resulted in an annual average of 1.04 million
      days of excess hospital stay and $2.72 billion excess cost. CONCLUSIONS:
      Identification of independent risk factors suggests areas for quality improvement
      initiatives. Post-operative infection carries substantial clinical and financial
      burdens in the United States, and further analysis of the associated costs is
      needed to identify areas for intervention to reduce this burden.

PMID- 30183519
TI  - Intermittent upper and lower body perfusion during circulatory arrest is safe for
      aortic repair.
AB  - INTRODUCTION: We report our initial surgical experience of intermittent upper and
      lower body retrograde perfusion during aortic repair under circulatory arrest.
      METHODS: Between 2007 and 2015, 148 consecutive patients underwent surgical
      aortic repair using moderate hypothermic circulatory arrest with intermittent
      upper and lower body retrograde perfusion. RESULTS: All patients underwent
      ascending aorta replacement; eight had hemiarch replacement (5.4%) and 92 had
      aortic root surgery (62.2%). Twenty-nine patients (19.6%) had re-operations and
      60 patients (40.5%) had concomitant procedures. The mean duration of circulatory
      arrest was 23.2 +/- 5.4 minutes (range 13-48 minutes). Hospital length of stay
      was 11.3 +/- 16.9 days (median 7.0 days; interquartile range [IQR] 6 days).
      Complications included death in 0.7%, stroke in 3.4%, respiratory failure in
      12.8%, renal replacement therapy in 2.0% and re-exploration for bleeding in 0.7%.
      Peak renal and hepatic biomarkers were: creatinine 1.2 +/- 0.3 mg/dL, aspartate
      aminotransferase (AST) 291 +/- 1112 U/L (IQR 91.8 U/L), alanine aminotransferase
      (ALT) 212 +/- 924 U/L (IQR 43.0 U/L) and total bilirubin 1.2 +/- 0.9 mg/dL. Peak
      lactate was 5.0 +/- 3.3 mmol/L (IQR 3.3 mmol/L) and the mean time to
      normalization (<2 mmol/L) was 14.3 +/- 14.0 hours. CONCLUSIONS: Intermittent
      upper and lower body retrograde perfusion during circulatory arrest is safe for
      aortic repair, resulting in low morbidity and mortality. There were only modest
      rises in hepatic and renal injury biomarkers as well as the rapid clearance of
      lactate. These findings support the continued study of this technique to reduce
      end-organ dysfunction during circulatory arrest, including expansion to patients
      with longer circulatory arrest duration and a direct comparison with conventional
      circulatory arrest without retrograde upper and lower body perfusion.

PMID- 30183520
TI  - Scoring System to Predict the Risk of Surgical Site Infection in Patients with
      Esophageal Cancer after Esophagectomy with Cervical Anastomosis.
AB  - BACKGROUND: Surgical site infection (SSI) surveillance has become increasingly
      important during the peri-operative period of esophagectomy with cervical
      anastomosis (McKeown esophagectomy). This study sought to clarify the risk
      factors for SSI and to develop a stratification scoring system to predict SSI
      after esophagectomy with cervical anastomosis. PATIENTS AND METHODS: All patients
      who underwent elective esophagectomy with cervical anastomosis were studied
      between January 2010 and December 2016 in the Chinese Academy of Medical Sciences
      Cancer Hospital (CAMS). Univariable analysis and multivariable logistic
      regression were used to screen the independent risk factors. A risk
      stratification scoring system was developed based on multivariable logistic
      regression parameters. The model derivation set involved 711 consecutive cases,
      and the validation set involved 168 consecutive cases. RESULTS: In the model
      derivation set, there were 711 patients, of whom 146 were found to have SSI and
      the incidence rate was 20.53%. Multivariable analysis found that SSI was
      associated independently with the following adverse risk factors: peripheral
      vascular disease, prior chest surgery, no pre-operative surgical antibiotic
      prophylaxis (SAP) administration within 120 minutes prior to incision, low serum
      albumin, and low pre-albumin at post-operative day zero to three, respectively.
      Each of these factors contributed one point to the risk score and a risk
      stratification scoring system was established. The SSI rates were increased
      gradually in the low, intermediate, high, and extremely high-risk groups (p <
      0.001). The area under the receiver operating characteristic (AUROC) curve was
      0.706 for the logistic regression model and 0.704 for the scoring system. In the
      validation set, the model performed equivalently (AUC = 0.824). CONCLUSIONS: The
      validated stratification scoring system could predict accurately the risk of SSI
      after esophagectomy with cervical anastomosis. This could be helpful in the
      selection of high-risk patients requiring frequent monitoring and more aggressive
      interventions to decrease the incidence of SSI.

PMID- 30183521
TI  - Can the Plasma Concentration Ratio of Triglyceride/High-Density Lipoprotein
      Cholesterol Identify Individuals at High Risk of Cardiovascular Disease During 40
      Year Follow-Up?
AB  - BACKGROUND: The plasma concentration ratio of triglyceride (TG)/high-density
      lipoprotein cholesterol (HDL-C) is a simple way to estimate insulin resistance.
      We aimed to evaluate the TG/HDL-C ratio as a simple clinical way to identify
      apparently healthy individuals with insulin resistance and enhanced risk of
      future cardiovascular disease (CVD). METHODS: One thousand seven hundred twenty
      men, aged 50 years, free from diabetes and CVD when evaluated at baseline in 1970
      1974 were followed for 40 years regarding incident CVD (myocardial infarction
      and/or ischemic stroke, n = 576). RESULTS: Participants with a high TG/HDL-C
      ratio (highest quartile >1.8) at baseline were more insulin resistant, with a
      significantly more adverse cardiometabolic risk profile (P < 0.001) at baseline,
      compared with those with a lower ratio. This group also showed an increased risk
      of CVD [hazard ratio, HR 1.47 (95% confidence interval 1.26-1.93) P < 0.001].
      Fourteen percent of subjects with metabolic syndrome, in whom insulin resistance
      is increased, were also at enhanced CVD risk [HR 1.75 (1.42-2.16) P < 0.001].
      CONCLUSIONS: Twenty-five percent of apparently healthy 50-year-old men with the
      highest TG/HDL-C plasma concentration ratio had a significantly more adverse
      cardiometabolic profile at baseline, and developed more CVD over the next 40
      years, compared with those not meeting this cut point. Determining the TG/HDL-C
      ratio in middle-aged men provided a simple and potentially clinically useful way
      to identify increased risk of developing CVD in persons free of diabetes or
      manifest CVD.

PMID- 30183522
TI  - Relationship between Th1 and Th2 cytokine serum levels and immune response to
      Hepatitis B vaccination among Egyptian health care workers.
AB  - Hepatitis B virus (HBV) vaccination leads to both humoral and cellular immune
      responses and results in protecting levels of specific antibodies. The immune
      response to the vaccine and production of T-helper 1 (Th1) and Th2 cytokines vary
      among the individuals. Thus we aimed to investigate the relationship between
      Th1/Th2 cytokine serum levels and antibody production after HBV vaccination,
      hoping to improve the effectiveness of vaccination. A total of 90 health care
      workers had been vaccinated with triple doses of HB vaccine at 0, 1, and 6 months
      intervals. Two months after the third dose, anti-HBs titer, interferon gamma (INF
      gamma), and interleukin (IL)-13 serum levels were measured. There were 16 low
      responders (anti-HBs = 10-150 IU/L), 41 moderate-responders (anti-HBs> 150< 1000
      IU/L), and 33 high-responders (anti-HBs = 1000 IU/L). IFN-gamma and IL-13 serum
      levels showed significant positive correlation with anti-HBs titer. We concluded
      that, decreased serum level of IFN-gamma (Th1 cytokine) and IL-13 (Th2 cytokine)
      was associated with diminished production of anti-HBs antibodies after HB
      vaccination, suggesting that IFN-gamma and IL-13 could play a significant role in
      the immune response to HB vaccination and could be used as vaccine adjuvants.

PMID- 30183524
TI  - Enhanced Interrogation: Inside the Minds and Motives of the Islamic Terrorists
      Trying to Destroy America.

PMID- 30183523
TI  - Determining Factors of Arterial Stiffness in Subjects with Metabolic Syndrome.
AB  - BACKGROUND: Metabolic syndrome (MS) is a clustering entity characterized by
      obesity, hypertension, hyperglycemia, dyslipidemia, and insulin resistance. Early
      detection of atherosclerosis is important in patients with MS because
      cardiovascular diseases are the main cause of mortality in these patients.
      METHODS: We aimed to investigate the factors influencing arterial stiffness,
      pulse wave velocity, and the augmentation index, respectively, in 150 subjects
      with MS (94 women and 56 men; mean age 60.56 +/- 9.8 years). Arterial stiffness
      was measured using the TensioMedTM Arteriograph. We tested the relationship
      between arterial parameters and insulin resistance measured by the determination
      of insulinemia (the ELISA method) and the homeostasis model assessment index
      (HOMA). RESULTS: In multivariate analysis we identified the independent factors
      that influence arterial stiffness: systolic blood pressure (coefficient of
      determination 3.586; P < 0.0001), serum triglycerides (coefficient of
      determination 3.579; P < 0.0001), and age (coefficient of determination 3.510; P
      = 0.001) are independent predictive factors for pulse wave velocity. The
      independent predictive factors of the augmentation index were the body mass index
      (coefficient of determination 0.55; P = 0.009), the presence of diabetes mellitus
      (coefficient of determination 4.7; P = 0.03), mean arterial pressure (coefficient
      of determination 0.44; P < 0.0001), gender (coefficient of determination 9.2; P <
      0.0001), age (coefficient of determination 0.3; P < 0.0001), and heart rate
      (coefficient of determination 0.66; P < 0.0001). Insulin resistance (HOMA index)
      was a predictor of the brachial augmentation index (beta coefficient 3.4; P <
      0.001) and was not a predictor of pulse wave velocity (beta = -0.3; P = 0.6) in
      our study. CONCLUSIONS: Given the known predictive value of pulse wave velocity
      for cardiovascular events, identifying the factors responsible for the increase
      in arterial stiffness is extremely important.

PMID- 30183525
TI  - Human Cases of Rift Valley Fever in South Africa, 2018.
AB  - Major Rift Valley fever (RVF) epidemics in South Africa occur at irregular
      intervals, usually spanning several decades, with human cases rarely reported in
      the absence of widespread outbreaks in livestock. This report describes four
      cases of RVF in farm workers associated with an isolated outbreak on a sheep farm
      in the Free State Province of South Africa, in 2018. In contrast to the last
      major RVF epidemic in South Africa in 2010-2011, where detection of human cases
      served as an alert for an ongoing outbreak in livestock, the current isolated
      outbreak was first detected in livestock, and human cases recognized following
      subsequent epidemiological investigation. This highlights the importance of early
      recognition of livestock cases in reducing risk and impact of a subsequent RVF
      epidemic in humans. People working with animals should be aware of transmission
      routes and take precautions to minimize risk of infection.

PMID- 30183527
TI  - 47. Jahrestagung Deutsche Gesellschaft fur Angiologie - Gesellschaft fur
      Gefabetamedizin e.V.

PMID- 30183526
TI  - Mediators in the Association Between Affective Temperaments and Suicide Risk
      Among Psychiatric Inpatients.
AB  - BACKGROUND: Affective temperaments have been shown to be related to psychiatric
      disorders and suicidal behaviors. Less is known about the potential contributory
      role of affective temperaments on suicide risk factors. In the present study, we
      investigated whether the effect of affective temperaments on suicide risk was
      mediated by other variables, such as hopelessness, mentalization deficits,
      dissociation, psychological pain, and depressive symptoms. METHODS: Several
      assessment instruments, including the Mini International Neuropsychiatric
      Interview (MINI); the Temperament Evaluation of Memphis, Pisa, and San Diego
      Autoquestionnaire (TEMPS-A); the Beck Hopelessness Scale (BHS); the Gotland Male
      Depression Scale (GMDS); the Dissociative Experiences Scale (DES); the
      Psychological Pain Assessment Scale (PPAS); and the Mentalization Questionnaire
      (MZQ), were administered to 189 psychiatrically hospitalized patients (103 women,
      86 men) in Rome, Italy. RESULTS: In single-mediator models, hopelessness,
      depressive symptoms, and mentalization, but not psychological pain or
      dissociation, were significant mediators in the association between prevalent
      temperament and suicide risk. In a multiple-mediator model, a significant
      indirect effect was found only for depression. Results demonstrated that patients
      with negative temperaments reported higher suicide risk, psychological pain,
      hopelessness, and depression, and less mentalization than patients with no
      prevalent temperament or hyperthymic temperaments. CONCLUSIONS: Hopelessness,
      depression, and mentalization are all factors that mediate the relation between
      affective temperaments and suicide risk. Identifying factors that mediate the
      effects of affective temperamental makeup on suicide risk should enhance
      screening and intervention efforts.

PMID- 30183528
TI  - The Role of Impulsivity and Expectancies in Predicting Marijuana Use: An
      Application of the Acquired Preparedness Model.
AB  - Impulsivity and substance use covary. Smith and Anderson's acquired preparedness
      model proposes that impulsivity predicts substance use through a mediational
      model such that substance use expectancies mediate the relation between
      impulsivity and drug use. The present study seeks to examine the relation between
      positive urgency, an important component of impulsivity with specific relations
      to substance use behavior, marijuana expectancies, and marijuana use patterns.
      The study focused on a sample of frequent marijuana users (n = 3,616) and
      assessed positive urgency using the UPPS-P, expectancies using the Biphasic
      Marijuana Effects Scale, an adapted form of the Biphasic Alcohol Effects Scale to
      measure the sedative and stimulant properties of marijuana, and also assessed use
      patterns. Findings suggest that stimulant expectancies predict heavier, more
      frequent marijuana use than sedative expectancies and that marijuana expectancies
      vary based on the limb of marijuana intoxication. Examination of the acquired
      preparedness model revealed that positive urgency's link to marijuana use was
      fully mediated by expectancies.

PMID- 30183530
TI  - Online Only Articles.
AB  - On occasion we receive manuscripts that we would like to publish, but do not have
      the page room to include in the print journal. For the full article, please go to
      www.jopdentonline.org or enter the provided address into your address bar.

PMID- 30183529
TI  - Evaluation of a Field-Deployable Insulated Isothermal Polymerase Chain Reaction
      Nucleic Acid Analyzer for Influenza A Virus Detection at Swine Exhibitions.
AB  - Rapid detection of influenza A virus (IAV) at swine exhibitions, where zoonotic
      transmission has occurred, can allow exhibition officials to quickly implement
      mitigation strategies and reduce public health risk. While laboratory diagnostic
      methods using PCR exist, pen-side detection of IAV can reduce lag time between
      sample collection and results. Portable insulated isothermal PCR (RT-iiPCR) has
      been used for point-of-care pathogen detection in veterinary medicine. This study
      compared laboratory methods of real-time reverse transcription PCR (rRT-PCR) to
      RT-iiPCR to determine the potential effectiveness of RT-iiPCR for detection of
      IAV in swine in the field. Two methods of extraction (magnetic bead and spin
      column) and the two PCR platforms were used in a crossover study design to detect
      IAV in nasal wipes of 150 individual swine from one exhibition. Magnetic bead
      extraction is considered the laboratory gold standard while spin-column
      purification is considered the field-deployable method. IAV RNA was detected in
      17 samples using Mag/rRT-PCR (reference assay) and 16 samples using Mag/RT-iiPCR
      (Sensitivity-S 76.5%), whereas only 14 samples using Spin/rRT-PCR (S 88.2%) and
      12 samples using Spin/RT-iiPCR (field method) (S 58.8%) were positive,
      demonstrating a reduction in detection of viral RNA using column purification.
      There is moderate agreement (Cohen's kappa = 0.6575) between Mag/rRT-PCR and
      Spin/RT-iiPCR. There is good agreement between both PCR assays when using the
      same method of extraction (Mag: Cohen's kappa = 0.8203, Spin: Cohen's kappa =
      0.7642). RT-iiPCR requires testing of 10 more samples than the rRT-PCR to detect
      disease at the 95% confidence level in a population of 300 animals with a disease
      prevalence of 20%. In conclusion, although there is some reduction in
      sensitivity, RT-iiPCR used in conjunction with spin-column purification is an
      acceptable method of IAV in swine detection at exhibitions where it may help
      reduce lag time and allow for rapid control of an IAV outbreak.

PMID- 30183531
TI  - Dynamic and Static Flexural Appraisal of Resin-based Composites: Comparison of
      the ISO and Mini-flexural Tests.
AB  - The objective of this study was to determine the influence of specimen dimension
      and conditioning medium on the dynamic and static flexural properties of resin
      based composites (RBCs). One conventional (Filtek Z350) and two bulk-fill RBCs
      (Filtek Bulk-fill and Beautifil-Bulk Restorative) were evaluated. Bar-shaped
      specimens with dimensions 25 * 2 * 2 mm (ISO flexural [IFT]) or 12 * 2 * 2 mm
      (mini-flexural [MFT]) were fabricated using customized stainless-steel molds,
      finished, measured, randomly divided into two groups, and conditioned in air or
      artificial saliva (SAGF) for seven days at 37 degrees C. The specimens (n=10)
      were then subjected to dynamic and static three-point flexural testing. Data for
      storage modulus, loss modulus, loss tangent, flexural strength, and modulus were
      computed and subjected to t-test, analysis of variance/Tukey test, and Pearson
      correlation at a significance level of alpha = 0.05. For both IFT and MFT,
      significant differences in dynamic and static flexural properties were more
      prevalent between materials after storage in saliva. For both conditioning
      mediums, the strongest correlation between IFT and MFT was observed for flexural
      strength. While significant positive correlations were observed for all flexural
      properties with saliva, no significant correlations were detected for loss
      tangent and flexural modulus with air. For both IFT and MFT, storage in saliva
      appeared to be more discriminative than storage in air. As moderate to strong
      positive relationships exist between IFT and MFT for dynamic and static flexural
      properties, the mini-flexural test holds promise as a replacement for the ISO
      4049 in view of its clinical relevance and greater efficiency.

PMID- 30183533
TI  - Thoughts on Dentistry-2018.

PMID- 30183535
TI  - Chemical Interaction and Interface Analysis of Self-Etch Adhesives Containing 10
      MDP and Methacrylamide With the Dentin in Noncarious Cervical Lesions.
AB  - OBJECTIVES: To characterize the chemical interactions and analyze the interface
      of adhesive systems containing 10-methacryloyloxydecyl dihydrogen phosphate (10
      MDP) and N-methacryloyl glycine (methacrylamide) functional monomers with the
      dentin in noncarious cervical lesions (NCCLs) compared with artificial defects
      (ADs). METHODS AND MATERIALS: Twenty human teeth with natural NCCLs on the buccal
      surface were used. Class V cavities, similar to NCCLs, were created on the
      lingual surface to serve as controls. Teeth were randomly allocated to two groups
      according to the functional monomer in the adhesive (N=10): G1, 10-MDP; and G2,
      methacrylamide. NCCLs and ADs were characterized by their mineral composition
      (MC) and degree of demineralization (DD) using micro-Raman spectroscopy,
      adhesive/dentin chemical interactions (CIs) were assessed with infrared
      photoacoustic spectroscopy, and interface morphology was evaluated with scanning
      electron and light microscopy. MC, CI, and DD data were submitted to Shapiro-Wilk
      and Student t-tests ( p<0.05). RESULTS: Compared with ADs, dentin in NCCLs was
      hypermineralized ( p<0.05). In G1, CI, and DD in the first 2 MUm, and adhesive
      projections in NCCLs and ADs interfaces were similar. Additionally, a thin layer
      of dentin collagen was observed in ADs, while it was hardly present in NCCLs. In
      G2, although CI could not be identified, changes in the mineral components were
      observed. The DD in the ADs and NCCLs were statistically similar, while SEM
      showed a lack of adhesion at NCCLs interface. DD and collagen exposure in the ADs
      and NCCLs were more pronounced than in G1. CONCLUSIONS: Results suggest that the
      G1 adhesive could be applied directly on the superficial sclerotic layer in
      NCCLs. In contrast, previous cavity preparation should be conducted to improve
      the micromechanical interaction of G2 with the dentin.

PMID- 30183536
TI  - Original and Repair Bulk Fracture Resistance of Particle Filler and Short Fiber
      Reinforced Composites.
AB  - OBJECTIVE: This study aimed to evaluate the original (OR) and repair (RR)
      fracture resistance of a semi-interpenetrating polymer network (semi-IPN)-based
      short fiber-reinforced composite compared to dimethacrylate-based composite
      materials by means of the V-notch test. METHODS AND MATERIALS: Circular specimens
      (5*2 mm) with a centrally machined 90 degrees  V-shaped notch were prepared. Four
      bulk fill (Filtek Bulk Fill, Venus Bulk Fill, TetricEvo Ceram Bulk Fill, SDR),
      three microfilled hybrid (GC-Anterior, GC-Posterior, Z250), one nanofilled
      (SupremeXTE), and two short fiber-reinforced (Alert, everX Posterior) composites
      were selected. EverX Posterior was the semi-IPN material. Specimens (n=12/group)
      were either dry or water stored for 7 and 30 days, respectively, at 37 degrees C
      and then loaded in two-point load until fracture. One-half of each tested
      specimen was used for the repair procedure. Repairing surfaces were diamond-bur
      ground, etched, and treated with silane containing universal adhesive (Scotchbond
      Universal) before repair. RESULTS: Three-way analysis of variance revealed a
      significant statistical difference between the groups ( p<0.05). The fracture
      resistance of dry-stored groups was greater than that of water-stored groups. The
      highest OR was observed for dry-stored Alert (23.4 N/mm), which significantly
      deteriorated in water (17.4 N/mm) ( p<0.05). The highest RR was observed for
      everX Posterior (20.0 N/mm), which did not deteriorate in water significantly
      (19.0 N/mm) ( p>0.05). The everX Posterior preserved the specimens' integrity at
      the final fracture load (ductile fracture), whereas all other materials fractured
      into two halves at the interface (adhesive failure). CONCLUSIONS: The only
      material that provided enhanced repair strength that was close to the original
      cohesive strength of the material was everX Posterior. The endurance of repaired
      restorations can be improved by using semi-IPN-based filling material.

PMID- 30183537
TI  - Tailored Dentistry: From "One Size Fits All" to Precision Dental Medicine?
AB  - Over the past 30 years and fueled by both a rapidly evolving understanding of
      dental diseases and technological advances in diagnostics and therapy, dentistry
      has been changing dramatically. Managing dental caries and carious lesions had,
      for nearly a century, encompassed only a small number of basic concepts that were
      applied to virtually all patients and lesions, namely, invasive removal of any
      carious tissue regardless of its activity or depth and its replacement with
      restorative materials (amalgams or crowns for most of the past) or tooth removal
      and prosthetic replacement. Grounded in a deeper understanding of the disease
      "caries," its management-aiming to control the causes of the disease, to slow
      down or alleviate existing disease, and, only as a last resort, to remove its
      symptoms using a bur or forceps-has become more complex and diverse. In parallel
      and at nearly unprecedented speed, our patients are changing, as mirrored by
      ongoing debates as to the demographic and, with it, the social future of most
      high-income countries. This article describes how these changes will have a
      profound future impact on how we practice dental medicine in the future. It will
      deduce, from both demographic and epidemiologic trends, why there is the need to
      apply not one but rather the whole range of existing evidence-based concepts in
      an individualized (personalized) manner, hence increasing the effectiveness and
      efficiency of dental management strategies, and also describe how these
      strategies should be tailored according not only to our patients (their age and
      risk profiles) but also to the specific tooth (or site or lesion).

PMID- 30183538
TI  - Recovery homes: A social network analysis of Oxford Houses for Native Americans.
AB  - Social network data were collected among residents of an Oxford House (OH)
      recovery home, which was located on Suquamish Tribal territory. Data were
      collected on the social connections of eight male residents (including four
      Native Americans and four non-Native Americans) using a social network
      instrument. A number of social network relationship types were examined,
      including friendship, trust, and mentorship. Social network data assessed
      included diameter, reciprocity, the average path length, cohesion, density,
      transitivity, and centrality. Findings indicated that the OH provided residents a
      well-integrated network with multiple sources of friendship, trust, and mentors.
      This is of importance as recovery from substance abuse is facilitated when
      recovering individuals are provided stable and well-functioning networks that
      foster social support, access to resources, and mentorship.

PMID- 30183539
TI  - Relations of religion with depression and loneliness in older sexual and gender
      minority adults.
AB  - OBJECTIVES: High levels of religious involvement have been associated with
      positive mental health outcomes in older adults. This study investigated whether
      the effects of religion on healthy aging could generalize to older LGBTQ adults.
      METHODS: This study examined religious affiliation in childhood versus at
      present, as well as the relationships of outness to religious community and
      religious engagement with depression and loneliness in 102 lesbian, gay, and
      bisexual cisgender, transgender, and questioning adults (LGBTQ) over the age of
      55. As part of a larger study, participants completed several questions and
      measures including: one outness to religious community item, 4 religious
      engagement questions, the Center for Epidemiological Studies Depression Scale,
      and the 8-item UCLA Loneliness Scale. RESULTS: Many older LGBTQ adults reported
      changes in religious affiliation from childhood to adulthood. Greater levels of
      outness to religious communities and lower religious engagement were related to
      lower levels of depression and loneliness. CONCLUSIONS: Findings suggest that
      outness to religious communities may be beneficial to the mental health of older
      LGBTQ adults. Higher levels of distress may lead to higher levels of religious
      engagement. CLINICAL IMPLICATIONS: Religion, especially those that are supportive
      of sexual minorities, may help to improve the well-being of older LGBTQ adults.

PMID- 30183540
TI  - Heterothallic sexual reproduction in three canker-inducing tree pathogens within
      the Fusarium torreyae species complex.
AB  - Fusarium zanthoxyli and F. continuum are sister taxa that are the etiological
      agents of canker disease of prickly ash (Zanthoxylum bungeanum) in northern
      China. These two pathogens, together with F. torreyae, the causal agent of canker
      disease of the critically endangered conifer Florida torreya (Torreya taxifolia)
      from northern Florida and southwestern Georgia, constitute a novel clade, the F.
      torreyae species complex. To assess their reproductive mode, a polymerase chain
      reaction (PCR) assay targeting the MAT1-1 and MAT1-2 idiomorphs was designed and
      validated, using MAT sequences mined from the whole-genome sequence of the three
      F. torreyae clade pathogens and several closely related fusaria. Results of the
      MAT idiomorph PCR assay indicated that isolates of the three pathogens were MAT1
      1 or MAT1-2. When MAT1-1 and MAT1-2 isolates of each species were crossed on
      carrot agar, all of the F. zanthoxyli (N = 30) and F. continuum (N = 3) isolates
      tested were female fertile, yielding mature perithecia with viable ascospores. By
      comparison, only one pairing of the five different isolates of F. torreyae
      produced perithecia; however, the majority of the asci in this cross aborted or
      produced fewer than eight ascospores. Of the three temperatures tested (i.e., 22,
      25, and 27 C), the optimal temperature for perithecium production was 22-25 C in
      F. zanthoxyli and 25 C in F. continuum and F. torreyae. Ascospore progeny from
      three separate crosses of F. zanthoxyli and F. continuum and one cross of F.
      torreyae were genotyped to assess whether they were the products of genetic
      recombination and sexual reproduction. Genotyping of 34-40 progeny from the F.
      zanthoxyli and F. continuum crosses confirmed that they were the products of
      sexual reproduction. However, only 36% of the progeny in the F. torreyae cross
      were recombinant, which was roughly half of the nonparental progeny expected with
      three markers segregating.

PMID- 30183541
TI  - Music and substance use: A meta-analytic review.
AB  - While previous research has documented a relation between music and substance use
      among consumers, to date, there are no meta-analytic reviews of the literature,
      making our meta-analysis the first in this area. Results from 31 studies,
      yielding a total of 330,652, indicated that music had a significant effect on
      substance use, with both music format and genre being significant contributors.
      The effect of music on substance use also varied by substance type. In addition,
      participant biological sex and location of data collection were found to moderate
      the effect of music on substance use. Theoretical implications are discussed
      along with directions for future research.

PMID- 30183542
TI  - Predictive Value of Lipid Accumulation Product, Fatty Liver Index, Visceral
      Adiposity Index for Metabolic Syndrome According to Menopausal Status.
AB  - BACKGROUND: The aim of this study is to investigate the value of clinical
      indicators of metabolic syndrome according to menopausal status in healthy Korean
      women. METHODS: The study included 3936 female patients who were managed at Pusan
      National University Hospital Health Promotion Center from 2008 to 2014. Each
      patient completed self-report questionnaires and underwent personal interviews
      with a healthcare provider to assess their past medical history such as any
      previous disease, medication and/or menstrual histories along with the
      measurement of her current body size. Lipid accumulation product (LAP), fatty
      liver index (FLI), visceral adiposity index (VAI), other anthropometric
      measurements, and laboratory results were evaluated regarding the patient's
      diagnostic status of metabolic syndrome and menopause. RESULTS: The prevalence of
      metabolic syndrome was 11.6% and that of premenopausal and postmenopausal group
      were 7.0% and 14.6%, respectively. By univariate analysis, the area under the
      curve of the receiver operating characteristic curve of LAP, VAI, and FLI were
      0.93, 0.93, and 0.93, respectively, in premenopausal group, and they were
      decreased in postmenopausal group, with the value of 0.89, 0.89, and 0.88,
      respectively. CONCLUSION: This study showed the predictive values of LAP, VAI,
      and FLI for metabolic syndrome upon the patient's status of menopause-such
      markers should be carefully applied in women of menopausal transition.

PMID- 30183543
TI  - Ageing and Globalization.

PMID- 30183545
TI  - ZeMo: An Open Source Water Quality Monitoring System for Aquaria.
AB  - Zebrafish and other aquatic organisms depend on careful monitoring and adjustment
      of water quality for health and survival. This ideally includes continuous
      monitoring of several water parameters, including temperature, pH, conductivity,
      and dissolved oxygen. However, manual readings can be laborious, and commercially
      available monitors are cost-prohibitive for many installations, especially in
      small laboratories and classrooms. To address these issues, we have created ZeMo,
      a high-end open-source water monitoring system that includes a touchscreen, web
      interface, and email alerts-making continuous water quality monitoring attainable
      for a wide range of aquarium installations.

PMID- 30183546
TI  - "Free to Say No": Evoking freedom increased compliance in two field experiments.
AB  - The evoking freedom or "but you are free" (BYAF) technique is a social influence
      tactic that offers recipients the freedom to accept or decline a request. This
      research tested the effectiveness of the evoking freedom technique in two field
      experiments. Participants were asked either to complete a survey (Experiment 1)
      or to allow a stranger to borrow their mobile phone to make a call (Experiment 2)
      on an urban university campus. Half of the requests involved language that evoked
      freedom, and half of the requests were direct. In both experiments, results
      showed significantly greater compliance in the evoking freedom condition. This
      research extends previous work by demonstrating the effectiveness of the
      technique using a high-stakes request and in a culture other than that of France,
      where the majority of evoking freedom studies have been conducted.

PMID- 30183544
TI  - Interethnic Variability in CYP2D6, CYP2C9, and CYP2C19 Genes and Predicted Drug
      Metabolism Phenotypes Among 6060 Ibero- and Native Americans: RIBEF-CEIBA
      Consortium Report on Population Pharmacogenomics.
AB  - Pharmacogenetic variation in Latin Americans is understudied, which sets a
      barrier for the goal of global precision medicine. The RIBEF-CEIBA Network
      Consortium was established to characterize interindividual and between population
      variations in CYP2D6, CYP2C9, and CYP2C19 drug metabolizing enzyme genotypes,
      which were subsequently utilized to catalog their "predicted drug metabolism
      phenotypes" across Native American and Ibero American populations. Importantly,
      we report in this study, a total of 6060 healthy individuals from Ibero-America
      who were classified according to their self-reported ancestry: 1395 Native
      Americans, 2571 Admixed Latin Americans, 96 Afro-Latin Americans, 287 white Latin
      Americans (from Cuba), 1537 Iberians, and 174 Argentinean Ashkenazi Jews.
      Moreover, Native Americans were grouped into North-, Central-, and South
      Amerindians (from Mexico, Costa Rica, and Peru, respectively). All subjects were
      studied for the most common and functional CYP2D6, CYP2C9, and CYP2C19 allelic
      variants, and grouped as genotype-predicted poor or ultrarapid metabolizer
      phenotypes (gPMs and gUMs, respectively). Native Americans showed differences
      from each ethnic group in at least two alleles of CYP2D6, CYP2C9, and CYP2C19.
      Native Americans had higher frequencies of wild-type alleles for all genes, and
      lower frequency of CYP2D6*41, CYP2C9*2, and CYP2C19*17 (p < 0.05). Native
      Americans also showed less CYP2C19 gUMs than the rest of the population sample.
      In addition, differences within Native Americans (mostly North vs. South) were
      also found. The interethnic differences described supports the need for
      population-specific personalized and precision medicine programs for Native
      Americans. To the best of our knowledge, this is the largest study carried out in
      Native Americans and other Ibero-American populations analyzing CYP2D6, CYP2C9,
      and CYP2C19 genetic polymorphisms. Population pharmacogenomics is a nascent field
      of global health and warrants further research and education.

PMID- 30183547
TI  - Determination of the transfer of lead and chromium from feed to raw milk in
      Holstein cows.
AB  - In this study, we aimed to determinate the transfer of lead (Pb) and chromium
      (Cr) from feed to raw milk in Holstein cows. Solutions of lead acetate and
      chromium (III) nicotinate were added together at different levels to individual
      portions of feed on a daily basis. Lead administration for the low-, middle- and
      high-dosage groups was controlled as 0.9, 1.8 and 3.6 g/day for 30, 30 and 25
      days, while chromium was feed at 0.47, 1.5 and 4.7 g/d for 40, 40, and 40 days,
      respectively. A sensitive graphite furnace atomic absorption spectrometry (GFAAS)
      method was developed and optimised with a respective limit of detection of lead
      and chromium found to be 1 and 5 MUg kg-1 raw milk. The optical wavelengths for
      detection of lead and chromium were 283.31 nm and 357.87 nm respectively. The
      results showed that the highest concentrations of lead in raw milk for the low-,
      middle- and high-dosage groups were 0.083 +/- 0.021, 0.215 +/- 0.064 and 0.232 +/
      0.035 mg kg-1, which displayed a positive correlation with dosage levels. In
      addition, a high dosage level accompanied a greater rate of loss of lead contents
      after dosing withdrawal. However, chromium concentrations maintained a relatively
      stable range around 0.1 mg kg-1 raw milk for all dosing groups and showed little
      transfer from feed to raw milk through the whole experiment.

PMID- 30183548
TI  - The Relation Between ADHD Medication and Mild Cognitive Impairment, as Assessed
      by the Montreal Cognitive Assessment (MoCA), in Patients Entering Substance Use
      Disorder Inpatient Treatment.
AB  - OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) frequently co-occurs
      with substance use disorders and has some overlapping symptoms with mild
      cognitive impairment, including executive functions. We wanted to investigate
      whether patients with ADHD have an excess risk of mild cognitive impairment-like
      symptoms, as defined by the Montreal Cognitive Assessment (MoCA). Second, we
      assessed the impact of ADHD medication on the dichotomized MoCA for patients with
      ADHD. METHODS: The participants in this study were 129 inpatients at seven
      treatment clinics in Norway. All were screened with the MoCA. We calculated
      relative risk estimates (RR) for scoring in the mild cognitive impairment range
      (< 26) for those having ADHD. Finally, we calculated the RR for the patients
      within the ADHD group who were taking medication. RESULTS: Of the 129
      participants included in the analyses, 38 (29.5%) scored below the MoCA threshold
      (< 26), and 24 (18.6%) had ADHD that was diagnosed before or during the inpatient
      treatment. Of the 105 participants without ADHD, 31 (29.5%) scored below the
      threshold. Seven (29.2%) of those with ADHD scored below the threshold. The risk
      of scoring in the mild cognitive impairment range for those with and without ADHD
      was equal (RR = 0.98). Of the 24 patients with ADHD, 9 (37.5%) were taking
      medication at the time of testing. One of the patients taking medication scored
      below the threshold compared to six of those not taking medication. This suggests
      a 72% lower risk of mild cognitive impairment-like symptoms when taking
      medication (RR = 0.28); however, the effect was not significant. CONCLUSIONS: We
      revealed no excess risk of mild cognitive impairment-like symptoms for the ADHD
      group. However, within the ADHD group, there was a possible lower risk of mild
      cognitive impairment-like symptoms for patients taking medication. These results
      suggest that there may be a confounding overlap of symptoms between ADHD and
      cognitive function screens that necessitates adequate assessment and treatment of
      ADHD before screening or measuring cognitive function.

PMID- 30183549
TI  - Response to Toi et al. (doi: 10.1089/neu.2018.5821): Determining if Cerebrospinal
      Fluid Prevent Recurrence of Chronic Subdural Hematoma: A Multi-Center Prospective
      Randomized Clinical Trial.

PMID- 30183550
TI  - One-step fabricated keratin nanoparticles as pH and redox-responsive drug
      nanocarriers.
AB  - Keratin is a promising material for building drug carriers due to their
      biocompatibility, reduction sensitivity, and biodegradability. Herein, we aim to
      develop acid and glutathione (GSH) dual-responsive keratin-based drug carriers
      with a one-step strategy. Keratin/DOX complexes were first prepared by means of a
      simple mixing approach, followed by desolvation and crosslinking to prepare
      keratin-based drug loaded nanoparticles (KDNPs). The as-prepared KDNPs showed
      negative-charged surface and globular morphology with the diameter of ca. 129 nm.
      The drug-loading rate was as high as 14% as a result of electrostatic attraction.
      Drug delivery profile showed that KDNPs performed pH and GSH dual responsiveness
      as well as charge reversibility in the simulated tumor microenvironment. MTT
      assay demonstrated that KDNPs exhibited enhanced inhibitory efficiency against
      A549 cells. Moreover, CLSM observation suggested that these KDNPs were
      internalized through endocytosis pathway. All of these results demonstrated that
      keratin based drug carriers had potential of tumor therapy.

PMID- 30183551
TI  - Physical activity and common tasks of California farm workers: California Heat
      Illness Prevention Study (CHIPS).
AB  - Farm workers are at risk of heat related illness (HRI), but their work rates that
      contribute to HRI have not been objectively assessed. The CHIPS study collected
      accelerometer data and characterized the physical activity of major farm tasks.
      Demographic information, work characteristics, and accelerometer data were
      collected from 575 farm workers in California. Each participating worker
      contributed measurements over one work shift. An ActicalTM accelerometer was
      attached securely to a belt worn at the hip. Data were collected at one-minute
      intervals throughout the work shift. A total of 13 major work-task categories
      were defined. The mean physical activity counts per minute (cpm) and percentage
      of the shift spent at moderate and/or vigorous levels of activity were described
      for each task. Multiple linear regression models were constructed to determine
      the worker and environmental characteristics contributing to the physical
      activity level. Mean levels of physical activity ranged from 700 cpm (workers who
      carry produce) to a low of 150 cpm 'ground pruners' who tend low level plants,
      with an overall mean of 345 cpm or 'light' activity (2 to <=3 metabolic
      equivalents). The environmental temperature was the major factor associated with
      physical activity. A 10 degrees C increase in the median temperature reduced the
      mean cpm by 135 [95% CI = 87, 193]. Age and the tasks of sorting, ground pruning,
      and harvesting low-level crops were also negatively and independently associated
      with mean cpm. Incentivized (piece rate) pay, multi-task and irrigator work were
      positively associated with cpm. An interaction was found between piece rate and
      sex. Men's activity significantly increased (p <0.001) by a mean of 95 cpm, [95%
      CI = 38.3, 150.7] if they were paid by the piece, but there was a non-significant
      association with women's activity level. Workers conducting multiple tasks,
      irrigators, men, and those earning incentivized (piece rate) pay had higher
      adjusted mean physical activity levels and are likely at increased risk of heat
      related illness on hot days.

PMID- 30183552
TI  - Effects of Whole-Grain Consumption on Selected Biomarkers of Systematic
      Inflammation: A Systematic Review and Meta-analysis of Randomized Controlled
      Trials.
AB  - : Whole grains have potential benefits in preventing cardiovascular diseases and
      diabetes; nevertheless, results from randomized clinical trials (RCTs) on
      inflammatory markers are controversial. The aim of this meta-analysis of RCTs was
      to examine the effect of whole grains on inflammatory markers A systematic
      literature search was conducted by using the online database of PubMed, Embase,
      Google Scholar, and Scopus for relevant studies up to November 2017, using
      Medical Subject Headings and other related keywords. Only studies that compared
      the effects of whole grains on inflammatory markers with refined grains were
      included. From more than 2278 articles, 17 RCTs met the inclusion criteria and
      were systematically reviewed. Weighted mean differences were estimated and pooled
      effect size was calculated by random effects model. Thirteen RCTs with 466
      participants were included in the meta-analysis. Whole-grain consumption had a
      significant effect on serum concentration of high-sensitivity C-reactive protein
      (hs-CRP; Hedges' g: -0.22; 95% confidence interval (CI): -0.45, 0.00; p = 0.047),
      interleukin-6 (IL-6; -0.28 pg/mL; 95% CI: -0.55, -0.02; p = 0.037) but did not
      result in a significant decline in serum concentration of tumor necrosis factor
      alpha (TNF-alpha; -0.12 pg/mL; 95% CI: -0.39, 0.15; p = 0.396). Significant
      heterogeneity was observed between studies for hs-CRP (I2 = 69.0%, p < 0.0001),
      IL-6 (I2 = 96.6%, p < 0.001), and TNF-alpha (I2 =  95.4%, p < 0.001). In
      sensitivity analysis, the effect of whole grain intake on hs-CRP, IL-6, and TNF
      alpha was not substantially modified by the result of a single study. Meta
      regression for duration showed no significant association between the duration of
      study and changes in serum C-reactive protein levels (beta coefficient = 0.006,
      standard error = 0.036; p = 0.870). CONCLUSIONS: This meta-analysis of RCTs
      suggested that whole grains might affect health status via improving systematic
      inflammation. Key teaching points: We conducted a systematic review and meta
      analysis of randomized controlled trials. Whole grains consumption was associated
      with lower serum levels of hs-CRP and IL-6. Whole grains cannot significantly
      decrease serum levels of TNF-alpha. We could not found any source for
      heterogeneity. The effect of whole grains on serum inflammatory biomarkers was
      independent from duration.

PMID- 30183554
TI  - PTSD From a Suicide Attempt: Phenomenological and Diagnostic Considerations.
AB  - OBJECTIVE: A suicide attempt is at least somewhat life-threatening by definition
      and is, for some, traumatic. Thus, it is possible that some individuals may
      develop posttraumatic stress disorder (PTSD) from a suicide attempt. METHOD: In
      this article, we consider whether one's suicide attempt could fulfill Diagnostic
      and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for a
      PTSD Criterion A event and contribute to the development of attendant PTSD
      symptoms (e.g., flashbacks, avoidance, shame/guilt, nightmares); discuss
      theoretical models of PTSD as they relate to suicide attempts; reflect on factors
      that might influence rates of suicide attempt-related PTSD; highlight
      methodological limitations that have hampered our understanding of suicide
      attempt-related PTSD; and posit areas for future scientific and clinical inquiry.
      RESULTS: Strikingly, the degree to which a suicide attempt leads to PTSD is
      unknown. CONCLUSIONS: We conclude with a call for research to systematically
      assess for suicide attempts alongside other potentially traumatic experiences
      (e.g., combat exposure, rape) that are included in standardized PTSD assessments.

PMID- 30183553
TI  - Injury of Adult Zebrafish Expressing Acvr1lQ204D Does Not Result in Heterotopic
      Ossification.
AB  - Fibrodysplasia Ossificans Progressiva (FOP) is a rare, autosomal dominant genetic
      disorder in humans characterized by the gradual ossification of fibrous tissues,
      including skeletal muscle, tendons, and ligaments. In humans, mutations in the
      Type I BMP/TGFbeta family member receptor gene, ACVR1, are associated with FOP.
      Zebrafish acvr1l, previously known as alk8, is the functional ortholog of human
      ACVR1. We previously created and characterized the first adult zebrafish model
      for FOP by generating animals harboring heat shock-inducible mCherry-tagged
      constitutively active Acvr1l (Q204D). Since injury is a known trigger for
      heterotopic ossification (HO) development in human FOP patients, in this study,
      we investigated several injury models in Acvr1lQ204D-expressing zebrafish and the
      subsequent formation of HO. We performed studies of Activin A injection,
      cardiotoxin (CTX) injection, and caudal fin clip injury. We found that none of
      these methods resulted in HO formation at the site of injury. However, some of
      the cardiotoxin-injected and caudal fin-clipped animals did exhibit HO at distant
      sites, including the body cavity and along the spine. We describe these results
      in the context of new and exciting reports on FOP, and discuss future studies to
      better understand the etiology and progression of this disease.

PMID- 30183555
TI  - Molecular Characterization of Trypanosoma cruzi in Infected Meccus pallidipennis
      in the Southern Region of the State of Mexico, Mexico.
AB  - PCR amplification and sequencing of Trypanosoma cruzi (T. cruzi) spliced-leader
      intergenic region of the mini-exon gene intergenic region (SL-IR) fragment was
      performed on intestinal tissue and fecal content DNA extracted from 19 Meccus
      pallidipennis (M. pallidipennis) specimens collected in the southern region of
      the State of Mexico. DNA sequence analysis from 49 bp T. cruzi SL-IR showed that
      all 19 samples corresponded to haplotype TcIa, and all of them were identical to
      GenBank sequence JQ028863. When extending the analysis to the whole 256 bp
      amplified sequence of the SL-IR, we found six sequences with a C insertion at
      position 10, one of which also presented a mutation (T/C) at position 54. One
      more sequence had an insertion (T) at position 223. Our findings suggest that two
      dominating TcIa clones are present in M. pallidipennis in the southern region of
      the State of Mexico. Interestingly, the SL-IR region of the dominating genotype
      was 100% identical to a circulating clone from Costa Rica present in humans,
      dogs, Triatoma dimidiata, and Panstrongylus rufotuberculatus. Future regional
      studies should explore the presence of this haplotype in humans and domestic
      animals.

PMID- 30183556
TI  - Multimorbidity of overweight and obesity alongside anxiety and depressive
      disorders in individuals with spinal cord injury.
AB  - OBJECTIVE: To compare the prevalence of anxiety/depression and overweight/obesity
      (Aim 1) and the multimorbidity of these conditions (Aim 2) in a sample of adults
      with and without spinal cord injury (SCI). Aim 3 was to examine whether
      overweight/obese individuals with SCI differ on the prevalence of
      anxiety/depressive disorders compared to non-overweight/obese individuals with
      SCI. DESIGN: Retrospective cohort study. PARTICIPANTS: Individuals >=16 years old
      who had patient encounters between January 1, 2011, and February 28, 2018. In
      total, 761 598 individuals were included, of which 3136 had SCI. MAIN OUTCOME
      MEASURES: Individuals were identified as diagnosed with SCI, anxiety and/or
      depressive disorders, and overweight/obesity using the International
      Classification of Diseases. RESULTS: Age-adjusted odds ratios (ORs) were
      calculated using logistic regression. In contrast to non-SCI individuals, those
      with SCI had increased odds of anxiety disorders (OR: 3.58, 95% CI [3.29-3.90]),
      depressive disorders (OR: 4.33, 95% CI [3.95-4.74]), and overweight/obesity (OR:
      3.08, 95% CI [2.80-3.38]). Pertaining to multimorbidity, individuals with SCI had
      increased odds of having overweight/obesity alongside anxiety disorders (OR:
      4.30, 95% CI [3.71-4.98]) and overweight/obesity alongside depressive disorders
      (OR: 4.69, 95% CI [4.01-5.47]) compared to those without SCI. Individuals with
      SCI who were diagnosed as overweight/obese had increased odds of having anxiety
      disorders (OR: 2.54, 95% CI [2.06-3.13]), and depressive disorders (OR: 2.70, 95%
      CI [2.18-3.36]), relative to non-overweight/obese individuals with SCI.
      CONCLUSIONS: This work is among the first to find evidence that individuals with
      SCI are at heightened odds of overweight/obesity alongside anxiety and/or
      depressive disorders. This early work holds clinical implications for treating
      these interrelated comorbidities in SCI.

PMID- 30183557
TI  - Preventing Sexual Abuse: Perspectives of Minor-Attracted Persons About Seeking
      Help.
AB  - The primary aim of this exploratory research was to gain information from minor
      attracted persons (MAPs) about their (a) formal and informal experiences with
      help-seeking for minor attraction, (b) perceived barriers to seeking help for
      concerns about minor attraction, and (c) treatment priorities as identified by
      consumers of these services. A nonrandom, purposive sample of MAPs ( n = 293, 154
      completed all questions) was recruited via an online survey. Results show that
      75% of participants did seek formal help from a professional; however, just less
      than half of them found the experience to be helpful. Characteristics of helpful
      therapeutic encounters included nonjudgmental attitudes, knowledge about minor
      attraction, and viewing clients in a person-centered and holistic way. Barriers
      to help seeking included uncertainty about confidentiality, fear of negative
      reaction or judgment, difficulties finding a therapist knowledgeable about MAPs,
      and financial constraints. Understanding or reducing attraction to minors were
      common treatment goals, but participants also prioritized addressing general
      mental health and well-being related to depression, anxiety, loneliness, and low
      self-esteem. Implications for effective and ethical counseling and preventive
      interventions for MAPs are discussed.

PMID- 30183558
TI  - Increased Methamphetamine Use among Persons Who Inject Drugs in Hai Phong,
      Vietnam, and the Association with Injection and Sexual Risk Behaviors.
AB  - Methamphetamine use has increased significantly in Southeast Asia in the last 5
      10 years, but there is little research on risk behaviors associated with the
      increase in this region. We evaluate injection and sexual risk behaviors
      associated with current methamphetamine use among heterosexual persons who inject
      drugs (PWID) in Hai Phong, Vietnam. We recruited 1336 PWID and assessed
      associations between methamphetamine use, injection and sexual risk behaviors,
      stratified by HIV serostatus. There were several statistically significant
      associations between methamphetamine use and sexual risk behaviors among HIV
      positive PWID, but we did not find any associations between methamphetamine use
      and injection risk behaviors. Methamphetamine may increase the likelihood of PWID
      transmitting HIV to non-injecting primary sexual partners, as it can reduce ART
      adherence and can lead to weakening of the immune system and increased HIV viral
      loads. All participants were injecting heroin, and methamphetamine use may
      interfere with opiate use treatment. Public health efforts should focus on the
      large increase in methamphetamine use and the associated sexual risk behaviors.
      Emphasis on sexual risk behavior, particularly among those who are HIV-positive,
      in conjunction with continued monitoring of ART adherence and HIV viral loads, is
      critical.

PMID- 30183559
TI  - Efficacy of Negative-Pressure Wound Therapy for Preventing Surgical Site
      Infections after Surgery for Peritonitis Attributable to Lower-Gastrointestinal
      Perforation: A Single-Institution Experience.
AB  - BACKGROUND AND PURPOSE: For patients at high risk, such as those with lower
      gastrointestinal perforations, it is important to establish a preventive method
      that reduces the incidence of surgical site infections (SSIs) significantly. We
      applied negative-pressure wound therapy (NPWT) as part of a delayed primary
      closure approach to prevent SSIs. This study evaluated the value of this
      technique. METHODS: We included prospectively 28 patients undergoing abdominal
      surgery for peritonitis caused by a lower-gastrointestinal perforation between
      May 2014 and November 2015. Historical controls comprised retrospective data on
      19 patients who had undergone primary suturing for managing peritonitis incisions
      for a lower-gastrointestinal perforation from January to December 2013. RESULTS:
      We found a significant association between the SSI incidence and the type of
      incision management (10.7% with NPWT and delayed closure vs. 63.2% with primary
      suturing; p < 0.001). There was no significant difference between the groups in
      the length of the hospital stay (22 days for NPWT and delayed closure vs. 27 days
      for primary suturing; p = 0.45). No severe adverse events were observed related
      to NPWT. CONCLUSION: The use of NPWT and delayed primary closure was an effective
      measure for preventing SSI in patients undergoing abdominal surgery for
      peritonitis caused by lower-gastrointestinal perforation.

PMID- 30183560
TI  - An Open-Source Husbandry Repository.
AB  - Electronic databases provide effective and efficient management of zebrafish
      colony operations, but commercially available options are expensive. In this
      study we have developed a free zebrafish management repository alternative using
      free Google applications. Husbandry information is logged into a Google Sheets
      based catalog through Google Form (GF) entries. Form autopopulation can be
      streamlined by barcodes, which can be generated and deciphered through free
      smartphone applications. The repository is capable of calculating pertinent
      husbandry dates from GF input and sending e-mail reminders to users for specified
      tasks. A Google application-based repository allows for a free simple zebrafish
      husbandry management solution.

PMID- 30183561
TI  - Cytogenetic Trends in Two Families of the Neotropical Catfishes: Heptapteridae
      and Pseudopimelodidae (Siluriformes).
AB  - Several neotropical Siluriformes groups suffered important taxonomic revisions
      based on the evaluation of morphological and molecular characteristics that allow
      the construction of new phylogenetic hypothesis. In the present study were
      cytogenetically analyzed six species belonging to Heptapteridae (Cetopsorhamdia
      iheringi, Phenacorhamdia tenebrosa, Rhamdella eriarcha, Pimelodella meeki,
      Pimelodella australis, Heptapterus mustelinus) and two to Pseudopimelodidae
      families (Microglanis cottoides and Microglanis cibelae) by means of differential
      staining techniques to describe more precisely cytogenetic similarities and
      differences. The diploid number of R. eriarcha with 2n = 58 and M. cibelae with
      2n = 56 were reported for the first time. Also, the lowest chromosome number (2n
      = 48) for P. tenebrosa was described. The chromosome-banding techniques for to
      put in evidence nucleolar organizers impregnated by silver nitrate ([AgNORs],
      chromomycin A3 [CMA3], and rDNA 18S) showed for all studied species conserved
      patterns, characteristic for each family. The rDNA 5S showed high variability
      among species or populations of both families, these regions could be simple or
      multiple, syntenic, or not with rDNA18S. The chromosome markers showed that both
      families are related not only from a morphologic point of view but also by their
      karyotypic characteristics, however, some of the present cytogenetic results
      evidence the importance of new morphologic, molecular, and phylogenetic studies
      to improve the knowledge of these fish groups.

PMID- 30183562
TI  - Psychometric properties of the Insomnia Severity Index in Ethiopian adults with
      substance use problems.
AB  - This study investigated the psychometric properties of the Insomnia Severity
      Index (ISI) in substance-using Ethiopian adults. A simple random sampling of
      houses and a purposive sampling selection was performed in Mizan city, Ethiopia
      (n = 406). Participants completed the ISI and a meta-cognition questionnaire and
      sociodemographic information. IBM SPSS software with Amos was used for data
      analysis. There was no major ceiling or floor effect in the ISI scores. The
      internal consistency (Cronbach's alpha = 0.68 and 0.78) and internal homogeneity
      (moderate to strong item-total ISI score correlations; r >= 0.47) were adequate.
      All of the ISI (item as well as total) scores correlated with the meta-cognition
      total scores (r = 0.16-0.44; p < .01). The exploratory factor analysis results
      were heterogeneous. However, the confirmatory factor analysis favored a 2-factor
      model. The ISI has good psychometric validity among Ethiopian adults with
      substance use.

PMID- 30183564
TI  - Being and becoming professionally other: Identities, voices, and experiences of
      U.S. trans* academics by E. N. Pitcher.

PMID- 30183563
TI  - Neurobehavioral Alterations in Zebrafish Due to Long-Term Exposure to Low Doses
      of Inorganic Arsenic.
AB  - Inorganic arsenic (As) is one of the most ubiquitous and toxic substances with
      widespread health effects on human populations and biodiversity. Although arsenic
      is a frequent surface water pollutant, there is scant evidence about
      neurotoxicity in aquatic species in different stages of development. In the
      present study, we investigated the neurobehavioral effects of chronic exposure to
      environmentally relevant doses of arsenic. We exposed zebrafish to 50 and 500 ppb
      during the larval, juvenile, and adult stage (from 4 h to 150 days
      postfertilization). We then used broad behavioral screening to evaluate motor
      function, social behavior, learning and memory, and anxiety-like behaviors. Our
      results show that arsenic exposure to 500 ppb alters motor function from the
      embryo to the adult stage. Furthermore, during the adult phase, associative
      learning and the sensorimotor response are affected with both high and low doses
      of As, respectively. Notably, exposure to 500 ppb of As induces behaviors
      associated with anxiety, during the juvenile and adult phase but not the larval
      stage, without changes in whole-body cortisol levels. These results indicate that
      chronic exposure to arsenic during their lifespan is capable of producing
      alterations in different behavioral markers in aquatic vertebrates.

PMID- 30183565
TI  - When Group Work Doesn't Work: Insights from Students.
AB  - Introducing group work in college science classrooms can lead to noticeable gains
      in student achievement, reasoning ability, and motivation. To realize these
      gains, students must all contribute. Strategies like assigning roles, group
      contracts, anonymous peer evaluations, and peer ratings all encourage student
      participation. In a class using these strategies, we conducted in-depth
      interviews to uncover student perceptions of group work in general and the
      utility of these support strategies. Students in both high- and low-performance
      groups still complained of unequal contributions while praising the social
      support provided by groups. Students who scored highly on tests were more likely
      to recognize the benefits of group work, regardless of their groups' overall
      performance levels, while lower-scoring students perceived group work as time
      consuming "busy work" with little cognitive benefit. Comments from anonymous peer
      evaluations differed only subtly between high- and low-performance groups.
      Numerical ratings on these evaluations did correlate with overall group
      performance. However, students in lower-performance groups assigned harsh ratings
      to their low-scoring members, while students in higher-performance groups were
      more generous in their ratings for low-scoring members. We discuss implications
      of relying on support strategies for promoting productive group work.

PMID- 30183566
TI  - Developing an Analytical Framework to Characterize Student Reasoning about
      Complex Processes.
AB  - Real-world processes are complex and require ideas from multiple disciplines to
      be explained. However, many science courses offer limited opportunities for
      students to synthesize scientific ideas into coherent explanations. In this
      study, we investigated how students constructed causal explanations of complex
      phenomena to better understand the ways they approach this practice. We
      interviewed 12 undergraduate science majors and asked them to explain real-world
      phenomena. From these interviews, we developed a characterization framework that
      described the reasoning patterns we found. In this framework, we identified three
      explanatory frames that differentiated the kinds of explanations students
      provided: a colloquial frame, wherein participants activated conceptual resources
      based on personal experience using everyday language; an emerging mechanistic
      frame, wherein participants used scientific concepts in semicoherent ways; and a
      causal mechanistic frame, wherein participants cohesively drew upon scientific
      conceptual resources to construct mechanistic explanations. Overall, the causal
      mechanistic frame was the least prevalent frame invoked by students. Instead,
      many drew on an emerging mechanistic frame and struggled to identify and apply
      scientific concepts to real-world scenarios. We advocate for incorporating
      opportunities to reason about real-world phenomena into undergraduate science
      curricula to provide students with experience integrating scientific concepts to
      explain real-world phenomena.

PMID- 30183567
TI  - Faculty Beliefs about Intelligence Are Related to the Adoption of Active-Learning
      Practices.
AB  - Mounting evidence of the efficacy of active learning has prompted educators to
      consider adoption of these practices in college-level classrooms. One tenet of
      active learning is that most, if not all, students have the ability to learn.
      Instructors' perspectives on learning, however, may or may not be aligned with
      this. One belief held by some educators is that intelligence is fixed, that is,
      some students are more intelligent and have a higher ability to learn than
      others. Instructors with a fixed mindset may not be convinced that their
      investment in developing active-learning materials will be as fruitful as the
      education evidence suggests, because these instructors may not believe that most
      students can grow in their learning. Here, we explored the relationship between
      fixed mindsets and the adoption of active-learning strategies. We found that
      instructors with higher fixed mindsets were less persuaded that active-learning
      strategies were a good idea and less likely to implement the teaching practices.
      Our research suggests that development initiatives should explicitly address
      educators' lay theories of intelligence ( fixed or growth mindset) to support
      successful implementation of active learning.

PMID- 30183568
TI  - Sustaining STEM Initiatives: The Challenge of a Worthy Investment.

PMID- 30183569
TI  - Conceptual Demography in Upper Secondary Chemistry and Biology Textbooks'
      Descriptions of Protein Synthesis: A Matter of Context?
AB  - This study investigates how the domain-specific language of molecular life
      science is mediated by the comparative contexts of chemistry and biology
      education. We study upper secondary chemistry and biology textbook sections on
      protein synthesis to reveal the conceptual demography of concepts central to the
      communication of this subject. The term "conceptual demography" refers to the
      frequency, distribution, and internal relationships between technical terms
      mediating a potential conceptual meaning of a phenomenon. Data were collected
      through a content analysis approach inspired by text summarization and text
      mining techniques. Chemistry textbooks were found to present protein synthesis
      using a mechanistic approach, whereas biology textbooks use a conceptual
      approach. The chemistry texts make no clear distinction between core terms and
      peripheral terms but use them equally frequently and give equal attention to all
      relationships, whereas biology textbooks focus on core terms and mention and
      relate them to each other more frequently than peripheral terms. Moreover,
      chemistry textbooks typically segment the text, focusing on a couple of technical
      terms at a time, whereas biology textbooks focus on overarching structures of the
      protein synthesis. We argue that it might be fruitful for students to learn
      protein synthesis from both contexts to build a meaningful understanding.

PMID- 30183571
TI  - Transforming STEM Education through Collaborative Leadership at Historically
      Black Colleges and Universities.

PMID- 30183570
TI  - Student Integration into STEM Careers and Culture: A Longitudinal Examination of
      Summer Faculty Mentors and Project Ownership.
AB  - It is widely recognized that the United States needs to attract and retain more
      people in science, technology, engineering, and mathematics (STEM) careers.
      Intensive undergraduate research experiences (UREs) are one of the few strategies
      shown to improve longitudinal student interest and persistence in STEM-related
      career pathways; however, less is known about the underlying process linking
      activities to positive outcomes. The tripartite integration model of social
      influences (TIMSI) provides a framework for understanding the social influence
      processes by which students integrate into STEM careers and culture. The current
      study used a longitudinal design and latent growth curve modeling to examine and
      predict the development of scientific research career persistence intentions over
      the course of an intensive summer URE. The latent growth curve analysis showed
      that student persistence intentions declined and rebounded over the course of the
      summer. Furthermore, the positive impact of faculty mentor role modeling on
      growth trajectories was mediated through internalization of science community
      values. In addition, project ownership was found to buffer students from the
      typical trend of declining and rebounding persistence intentions. The TIMSI
      framework illuminates the contextual features and underlying psychological
      processes that link UREs to student integration into STEM careers and culture.

PMID- 30183573
TI  - The power of culture and context on Hispanic/Latina teen pregnancy and birth in
      Oklahoma: provider and parental perspectives.
AB  - OBJECTIVE: To explore cultural-contextual factors that impact the high rate of
      Hispanic/Latina teen pregnancy in Oklahoma from the perspective of providers and
      parents. METHODS: Community Based Participatory Research at the Latino Community
      Development Agency in Oklahoma City; focus groups and in-depth interviews; 33
      service providers and 14 Hispanic/Latino parents. RESULTS: (a) The value of
      respect among Hispanic/Latino families is a risk factor for unplanned teen
      pregnancy. (b) Contextual aspects (i.e. local ideology, Mexican media,
      underfunded schools, permissive law enforcement in bars, lack of bilingual
      providers) place Hispanic/Latina female adolescents at greater risk of unplanned
      pregnancy. (c) Gender roles perpetuate inequality and deepen Hispanic/Latina
      females' vulnerability to unplanned pregnancy. CONCLUSIONS: In addition to
      currently implemented communication tools and parenting skills to talk with
      adolescents about sexual health topics, interventions need to consider
      preferences that may be rooted in cultural aspects that could hinder the
      application of learned skills.

PMID- 30183572
TI  - Epidemiology of Upper Extremity Soccer Injuries Among High School- and College
      Aged Players in the United States: An Analysis of the 1999-2016 NEISS Database.
AB  - BACKGROUND:: Although lower extremity injuries are more common than upper
      extremity injuries in high school- and college-aged soccer players, upper
      extremity injuries may be equally severe. The epidemiology of upper extremity
      injuries is poorly characterized in this population. HYPOTHESIS:: Upper extremity
      injuries are an important contributor to soccer-related morbidity among high
      school- and college-aged players. STUDY DESIGN:: Descriptive epidemiology study.
      LEVEL OF EVIDENCE:: Level 3. METHODS:: The National Electronic Injury
      Surveillance System (NEISS) is a nationally representative sample of 100 hospital
      emergency departments (EDs). Each record contains demographic and injury
      information. Records from 1999 to 2016 were analyzed, including patients between
      the ages of 14 and 23 years with a soccer-related injury sustained at school or
      during an athletic event. RESULTS:: A total of 1,299,008 high school- or college
      aged patients presented to the ED for a soccer-related injury from 1999 to 2016,
      of which 20.4% were in the upper extremity. Patients were predominantly male
      (58.0%) and high school-aged (81.4%). Males constituted a greater proportion of
      upper extremity injuries when compared with other injury locations (63.5% male
      for upper extremity). Upper extremity injuries were more likely to be fractures
      (43.7% vs 13.9%) and dislocations (7.1% vs 3.4%) and less likely to be
      strains/sprains (27.8% vs 56.6%). Males suffered more shoulder dislocations
      (81.8% males among patients with shoulder dislocation vs 57.8% among those with
      other injuries), finger dislocations (72.0% vs 58.0%), upper arm fractures (74.9%
      vs 57.6%), and forearm fractures (68.3% vs 57.3%). CONCLUSION:: Upper extremity
      injuries are frequent in high school- and college-aged soccer players presenting
      to the ED. Efforts to reduce soccer-related injuries should include strategies
      targeting the upper extremity, perhaps reducing the incidence of high-energy
      falls. CLINICAL RELEVANCE:: Efforts to reduce soccer-related injuries should
      include strategies targeting upper extremity injuries, particularly among males
      and college-aged players.

PMID- 30183574
TI  - Exploration of the Relationship Between Concussions and Depression Symptoms,
      Anxiety Symptoms, and Hazardous Drinking Among a Sample of College Students.
AB  - OBJECTIVE: In clinical and athlete populations, research has found that
      experiencing a concussion (or traumatic brain injury) is correlated with
      experiencing other psychiatric conditions, including depression and alcohol
      problems. However, less is known about concussion comorbidity in other population
      segments. The purpose of this study is to examine the relationships between
      concussions and depression symptoms, anxiety symptoms, and hazardous drinking
      among a large sample of college students (N = 1776) enrolled in a mandatory
      health course. METHODS: This study used an online health survey to examine
      concussion frequency (informal and formal diagnoses), sports-related concussions,
      depression symptoms, anxiety symptoms, and hazardous drinking in the sample.
      Bivariate and multivariate analyses were conducted to examine comorbid
      relationships between concussion frequency and the dependent variables of
      interest (anxiety symptoms, depression symptoms, and hazardous drinking).
      RESULTS: We found that 691 (39.1%) participants indicated having at least one
      concussion. Analyses indicated that concussion frequency scores of both formal or
      informal diagnoses were significantly associated with scores of depression
      symptoms, anxiety symptoms, and hazardous drinking. When examining concussion
      frequency scores of only formal diagnoses, only hazardous drinking evidenced a
      statistically significant relationship. In addition, participants who had a
      sports concussion had significantly higher concussion frequency scores and
      hazardous drinking scores than those who have had a concussion that was not sport
      related. CONCLUSIONS: The comorbid concussion relationships found in this study
      are consistent with those observed in clinical and athlete populations. It is
      important for college health professionals to be aware that concussion
      comorbidity is not limited to the athlete population and can impact the entire
      student body.

PMID- 30183575
TI  - Surgical Stress Response and Enhanced Recovery after Laparoscopic Surgery - A
      systematic review.
AB  - Background: Enhanced Recovery Program (ERP) is a multimodal perioperative
      protocol. Its feasibility and benefits on short term outcomes have been widely
      reported. These well described improvements, like shorter length of stay and
      early resumption of body's functions, represent the consequence of an attenuated
      surgical stress response (SSR). When this response is uncontrolled, it leads to
      postoperative complications and poor long-term outcomes. SSR can be easily
      monitored through the analyses of mediators in the bloodstream. Available
      evidences do not achieve to tell if ERP allows a measurable surgical stress
      reduction. In this review, we searched for papers investigating the surgical
      stress response and ERP applied to elective mini-invasive procedures, in order to
      better understand the level of evidence regarding the effectiveness of ERP in
      minimizing the surgical stress response. Materials and Methods: A systematic
      review of published literature was performed using PubMed, Cochrane, EMBASE and
      Google Scholar database, following the Preferred Reporting Items for Systematic
      Review and Meta-analysis (PRISMA) guidelines. Included studies concerned SSR
      analysis in ERP patients undergoing laparoscopic surgery through different
      surgical specialties. Eight studies with a total of 632 patients were included.
      Results: The three steps of SSR, endocrine, inflammatory and nutritional were all
      reported in the papers included in this review. Results showed no powerful
      evidence of difference in endocrine phase while an attenuated inflammatory
      response was reported for ERP patients when Interleukin-6 (IL-6) and C Reactive
      Protein (CRP) were dosed. Nutritional status was also preserved as albumin, pre
      albumin and transferrin had better values in these patients. Conclusions: ERP
      applied to different types of laparoscopic surgery has a role in reducing SSR.
      This can be shown by the analysis of mediators such as IL-6, CRP and nutritional
      markers.

PMID- 30183576
TI  - New Definitions of Sepsis and the Quest for Specific Biomarkers. Are the miRNAs
      the Answer?
AB  - Sepsis represents a systemic illness, characterized by life-threatening organ
      dysfunction induced by infection. Early diagnostic, evaluation of severity of
      sepsis with aggressive resuscitation and administration of appropriate
      antibiotics are associated with improved outcomes. In 2016 a new definition of
      sepsis (Sepsis-3) was proposed. The key element of sepsis-induced organ
      dysfunction is defined by "an acute change in total SOFA score >= 2 points
      consequent to infection". The use of SIRS criteria as identification of sepsis
      was abandoned and subcategory of severe sepsis was eliminated. A wide spectrum of
      biomarkers had been proposed for potential use in sepsis, more than in other
      diseases, outlying the complex pathophysiology of this condition. The first study
      reporting the clinical value of circulating miRNAs in sepsis showed that both
      leukocytes and plasma miR-150 levels are significantly reduced in sepsis patients
      compared with controls and correlate with sepsis severity. Several miRNAs were
      found differentially expressed in sepsis patients, but most of the published
      studies failed to find miRNA biomarkers that could differentiate sepsis from
      SIRS. A solution to this problem seems to be building and analyzing miRNA network
      in sepsis patients.

PMID- 30183577
TI  - The Value of Intraoperative Endoscopy and Manometry in the Surgical Treatment of
      Achalasia.
AB  - : Introduction: Achalasia is the most common esophageal motility disorder. So
      far, the treatment, which can be medical, endoscopic or surgical, provides only
      symptomatic relief. However, this can grant a normal life to the patients. We
      focused our study on the value of pre- and intraoperative endoscopy and manometry
      for improving outcome of surgical treatment. MATERIAL AND METHOD: This is a
      retrospective chart review of a cohort of patients diagnosed with achalasia at St
      Mary Clinical Hospital, Bucharest between 2013 and 2017. The objective of this
      study was the assessment of the immediate and long term efficacy of laparoscopic
      Heller myotomy associated with Dor anterior fundoplication, intraoperative
      endoscopy and intraoperative manometry, as well as the assessment of late post
      operative complications. The diagnosis of achalasia was based on symptoms, barium
      esophagogram, upper endoscopy and esophageal manometry. The immediate efficacy
      was assessed by comparing Eckhart score, LES pressure and LES vector volume
      before and after surgery. Results: In total, 47 patients, had surgical treatment
      for achalasia between 2013 and 2017. For 7 patients who failed prior endoscopic
      or surgical, this was the second therapeutic intervention. 39 patients underwent
      laparoscopic surgery, 30 patients had associated intraoperative endoscopy and, 22
      patients had associated intraoperative manometry. There was a significant
      improvement in mean Eckardt score (from 6,5 to 1,26, p 0,001), mean LES pressure
      (from 18,5 mmHg to 7 mmHg, p 0,001). Morbidity was 2,12 % and we have had 1
      recurrence and 2 postoperative esophagitis. Conclusions: At present, laparoscopic
      Heller myotomy with an anterior Dor fundoplication, is a standard indication in
      achalasia, proving its efficiency and safety. Intraoperative use of endoscopy is
      recommended and intraoperative manometry may provide additional information on
      the effectiveness of myotomy. Surgical treatment of achalasia should be performed
      in specialized, experienced centers.

PMID- 30183578
TI  - Impact of Surgery and Early Postoperative Outcomes After Radical Gastrectomy for
      Cancer.
AB  - Background: Surgery remains one of the most important part of the multimodal
      treatment of patients diagnosed with gastric cancer. Due to the fact that the
      consequences in terms of postoperative morbidity can delay the onset of
      postoperative chemotherapy or even can make the patient unfitted for adjuvant
      treatment, a thorough clinical evaluation of patient prior to surgery is
      mandatory. Methods: We performed a retrospective study, which included all the
      patients diagnosed with gastric cancer in which radical surgery was performed
      during a 5-year period in a single center. All the patients, tumour and surgery
      characteristics were used for a risk analysis for the occurrence of overall,
      medical and surgical complications. Results: There were 189 patients in whom
      radical surgery was performed, 100 (52.9%) total gastrectomies and 89 (47.1%)
      subtotal gastrectomies, without difference in term of postoperative morbidity.
      There were 25 (13.2%) cases of duodenal stump fistula, 15 (15%) cases of
      esojejunal fistula. On multivariate analysis albumin levels (OR 1.9, p=0.035),
      hypertension (OR 4.22, p=0.0311) and splenectomy (OR 3.91, p=0.048) were
      independent factors for overall complications, albumin levels (OR 1.91,
      p=0.0405), hypertension (OR 3.54, p=0.0444), neoadjuvant treatment (OR 3.97,
      p=0.01657) and splenectomy (Or 1.66 p=0.05) for medical complications; age (OR
      1.71,p=0.044), hypertension (OR 2.22, p=0.045) and albumin levels (OR 1.92,
      p=0.041) for surgical type complications. Conclusions: Postoperative morbidity
      after gastrectomy remains one of the most important factors that can impair the
      effectuation of a multimodal treatment protocol. Comorbidity factors, nutritional
      status and surgical technique are the key factors that can influence the amount
      and the consequence of a surgical complication.

PMID- 30183579
TI  - New Options in the Management of Cystic Echinococcosis - A Single Centre
      Experience Using Minimally Invasive Techniques.
AB  - OBJECTIVE: The aim of this study is to verify if the experience on 4 years in
      using minimally invasive techniques in the treatment of CE could match regarding
      the indications and results with the major studies on topic. METHOD: During
      03.2014 - 03. 2018 period, 38 PAIR, 28 MoCaT procedures and 7 percutaneous
      drainages have been performed at 51 patients from 76 cases of hydatid hepatic
      cysts (67,1%). There were 26 men and 25 women, and the age ranged from 19 to 78.
      7 patients have had 2 hydatid hepatic cysts or more and 2 procedures were
      performed at 3 of those patients; other 11 patients needed the second procedure
      during the surveillance. Results: The evolution of the patients was favorable,
      and the surveillance was 2 years postintervention at least. There were no major
      surgical adverse effects. We defined as an expected result obtaining a scar
      lesion or a small cavity with calcified walls (hyperechoic). Only 2 (3,9%)
      patients needed conversion to open surgery. The complications we have faced were
      represented by the cystic-biliary fistula in 15 cases (29,4%) and the re-opening
      of the cyst's cavity in 11 cases (21,67%). Conclusions: The percutaneous
      treatment of CE is safe and effective, following the correct assignation
      according with the cysts type. The percutaneous treatment of CE is an easier
      alternative to the open surgery and has lower rate of complications and relapses,
      and a shorter hospitalisation. Now routine, it becomes slighty the first option
      for invasive treatment of CE. The role of open surgery is restricted to CE with
      severe complications.

PMID- 30183580
TI  - Clinical Pattern of Surgical Crohn Disease Patients.
AB  - Backround/Objective: The aim of investigation was to evaluate if there is a
      pattern regarding the anatomical location of the disease and type of surgery
      performed/surgical indication. Also a analysis was performed regarding the
      complication rate in two subgroups deriving from urban and rural environments.
      Methods: Data was obtained from the medical records of patients with CD and
      centralized. Tests of statistical analysis included the CHY-SQUARE test and the
      results were presented as a retrospective, longitudinal study. Results: The group
      was formed of 60 patients. Patients with ileocolic disease were frequently
      diagnosed with obstruction and benefited from an enterectomy with anastomosis.
      Patients with colonic disease were frequently diagnosed with perforation and
      benefited from colectomy and stomy. Patients from rural areas had a milder
      evolution when compared with patients from urban enviroments. Conclusions:
      Although most patients with CD eventually require surgery, the indication could
      be anticipated by recognition of the concept of clinical patterns, and type of
      surgery required could be predicted if the clinical aspect of the patient/disease
      were identified.

PMID- 30183581
TI  - Prognostic Factors Analysis for Colon Cancer with Lymph Node Negative.
AB  - PURPOSE: The analysis of high risk relapse prognosis factors and their importance
      regarding recurrence risk for stage I and II colon cancer, according to TNM
      classification 8th edition, 2017. MATERIAL AND METHOD: We performed a
      retrospective analysis regarding the impact of prognosis factors for patients
      with high recurrence risk in stages I and II. We studied 99 patients with T2, T3
      and T4 tumors who suffered a curative resection and whom may or may not present
      indication for adjuvant chemotherapy according to histoprognostic factors and
      molecular biomarkers. Results: We performed a univariate Cox regression which
      highlighted that male sex is a risk factor for disease relapse (HR=5.53, p 0.05,
      IC95% = 1.29 to 23.73). Although with a low statistical significance effect, T4
      tumors seems to be associated with a poor prognosis regarding disease relapse (HR
      = 2.56, p = 0.06, IC95% = 0.94 to 6.99) compared to T2 and T3 tumors. Patients
      with d'MMR (MSI-H) seem to have a more favorable evolution compared to patients
      with p'MMR (MSS/MSI-L) - HR (d'MMR vs p'MMR) = 0.19, IC95% = 0.02 to 1.61, p =
      0.13. Conclusions: We believe that it would be useful for MSS / MSI to be
      systematically analyzed, our data suggesting a better response of d'MMR patients
      to adjuvant chemotherapy. The multivariate Cox regression did not identify
      independent risk factors of relapse.

PMID- 30183582
TI  - The Impact of Intraoperative Fluid Therapy and Body Temperature on Surgical Site
      Infection - Re-Assessment of a Randomized Trial.
AB  - : Background: Use of supplemental oxygen during surgery to reduce the incidence
      of SSI was investigated in the PROXI trial, which found no reduced frequency of
      SSI. Subsequently, it has been suggested that a restrictive fluid regimen and
      hypothermia in some patients could explain why no beneficial effect of
      supplemental oxygen was found. We evaluated the association between the
      occurrence of SSI and two perioperative factors, volume of infused fluid and body
      temperature (BT). Methods: We used data from the PROXI trial including 1,386
      patients undergoing laparotomy randomly assigned to receive 80% or 30% oxygen
      during surgery. A fluid infusion index (FII) was calculated for each patient as
      the volume of infused fluids/body weight/duration of surgery. Results: SSI
      occurred in 18.9% of the patients in the lower FII tertile group (OR=0.86;
      P=0.41), in 20.4% in the upper FII tertile group (OR=1.49; P=0.05), in 19.7% of
      the patients with hypothermia (OR=1.28; P=0.25) and in 25.0% with hyperthermia
      (OR=1.26; P=0.52). An increased risk of SSI (OR=3.15; P=0.01) was found in
      patients having both hypothermia and emergency surgery. CONCLUSION: A trend
      towards an increased risk of SSI was seen in patients who received a greater
      volume of intravenous fluid. No association was found between BT and SSI.

PMID- 30183583
TI  - Evaluation of Tumor Response Using Alpha-fetoprotein and Des-gamma-carboxy
      Prothrombin in Hepatocellular Carcinoma Patients Who Underwent Transarterial
      Chemoembolization.
AB  - : Introduction: The aim of the study is to evaluate the role of alpha-fetoprotein
      (AFP) and des-y-carboxy prothrombin (DCP) in the assessment of treatment response
      at one month in patients with hepatocellular carcinoma (HCC) treated with trans
      arterial chemoembolization (TACE). Methods: From March 2016 to April 2017 a
      number of 59 patients diagnosed with HCC were prospectively enrolled. A TACE
      procedure as initial treatment modality was performed in 41 patients. AFP and DCP
      serum levels were measured and clinical features were determined for all the
      patients that were included. The Wilcoxon rank test was used to compare variables
      at baseline and at one month after the procedure. Results: Treatment was
      performed in 86.4% of the patients diagnosed with HCC, 27 patients received a
      classical TACE procedure, 14 patients were treated with DEB-TACE, radiofrequency
      ablation was performed in 3 patients and 4 patients received a liver transplant
      as initial treatment. Systemic therapy with Sorafenib was started in 3 patients
      (5%) and in 8 cases no treatment was performed. AFP value significantly decreased
      at one month in patients that underwent TACE therapy (median value 240.3 vs.
      123.7 ng/mL, p=0.020). The same significant decrease was noted for DCP values
      (median value 1376.8 vs. 769 mAU/mL, p=0.0033). Both AFP (85.5 vs. 18.7 ng/mL,
      p=0.035) and DCP values (693.2 vs. 58.2 ng/mL, p=0.0003) were significantly lower
      only in subjects who achieved complete response after TACE and not in patients
      with partial response. In patients treated with TACE therapy, there was a down
      sizing of the maximum diameter of the tumor nodule (30 vs. 27 mm, p=0.02).
      CONCLUSION: There was a significant decrease of AFP and DCP values after complete
      response in HCC patients treated with TACE. DCP is a more effective tumor marker
      in predicting response than AFP, with no benefit found in their combination.

PMID- 30183584
TI  - The Role of Beta-7 Integrin and Carbonic Anhydrase IX in Predicting the
      Occurrence of de Novo Nonalcoholic Fatty Liver Disease in Liver Transplant
      Recipients.
AB  - : Background: Liver transplant (LT) recipients are at increased risk for
      developing metabolic syndrome. Early detection of NAFLD and other components of
      the metabolic syndrome is an important step in reducing morbidity and mortality.
      Methods: We assessed 60 liver transplant recipients for clinical and biological
      features, performed abdominal ultrasound and transient elastography (TE)
      Fibroscan(c) with controlled attenuation parameter (CAP), calculated non-invasive
      scoring systems APRI, FIB-4, NAFLD score, cardiovascular risk (Framingham risk
      score) and for the presence of metabolic syndrome and performed two biomarkers:
      beta 7 integrin and carbonic anhydrase IX. Results: Sixty liver transplant
      recipients underwent clinical and biochemical evaluation, abdominal ultrasound
      and TE with CAP. The median age was 56.5 years and the median time from
      transplantation 35 months. The Spearman correlation coefficient of beta 7
      integrin and the liver stiffness measurement values obtained via Fibroscan(c) we
      obtained a moderate correlation r=0.31, but a significant association (p=0.01).
      The univariate analysis showed significant association between both biomarkers
      and liver fibrosis assessed with a cut-off value of advanced fibrosis of 8.7 kPa.
      The carbonic anhydrase IX showed a better correlation when compared to the liver
      stiffness with a correlation coefficient of 0.43 and p-value=0.0007 and a
      moderate correlation when compared to both FIB-4 (r=0.27) and APRI (r=0.27) score
      for liver fibrosis but with a significant p value=0.04, respectively 0.03.
      CONCLUSION: We consider very important for our patients the development of new
      non-invasive biomarkers for early diagnosis of NAFLD and NASH, as the "gold
      standard" of liver biopsy is not easily accepted in clinical practice. Also NAFLD
      and NASH are dynamic processes that need prospective and repeated assessments, a
      need that cannot be met by the classical liver biopsy.

PMID- 30183585
TI  - Retroperitoneal Laparoscopic Radical Prostatectomy.
AB  - Introduction: Retroperitoneal Laparoscopic Radical Prostatectomy (RLRP) has been
      introduced in our department as the first line treatment for patients with
      localized prostatic cancer and life expectancy over 10 years. At the time, the
      surgical team had already extensive experience in minimally invasive urologic
      surgery. Our aim is to describe the laparoscopic technique we currently use and
      to analyze our oncologic and functional results. Patients and Methods: All the
      patients who underwent RLRP in our institution (PONDERAS ACADEMIC HOSPITAL) from
      January 2015 to March 2017 were included into a prospective study. The standard
      preoperative protocol included blood tests, prostate biopsy, pelvis MRI and bone
      scintigraphy, while the particular therapy was discussed and approved by the
      Institutional Multidisciplinary Tumor Board. In all the 45 cases, RLRP was
      indicated for localized prostate cancer. Results: The average
      patientA?AcA?A?A?A?s age was 68 years (range 45 A?AcA?A?" 74 years), mean
      preoperative prostate specific antigen (PSAi) level was 8 ng/mL (range
      3A?AcA?A?"15 ng/mL) and prostatic volume between 26 and 52 cc. The laparoscopic
      approach was completed in all 45 cases A?AcA?A?" no conversions to open surgery.
      Bilateral nerve sparing was performed in 7 cases (16%) and unilateral in 23 cases
      (51%). The mean operative time was 165 minutes (range 120 - 240 min), while the
      average blood loss was 255 mL (range 20A?AcA?A?"800) and two patients received
      blood transfusions. The mean catheterization time was 10 days (range 7A?AcA?A?"14
      days). Positive surgical margins were observed in 8 cases (17.7%). Overall, 86%
      and respectively, 93% of the patients were continent during the following 3 and 6
      months. 51% of the patients had erectile disfunction 6 month after the
      intervention. Four complications were encountered: intraoperatively - rectal
      injury (1 case) and postoperatively - bleeding (2 cases) and stenosis at the
      vesicourethral anastomosis (1 case). No mortality or late morbidity encountered.
      Conclusions: The radical laparoscopic prostatectomy is a safe and efficient
      procedure for localized prostate cancer with minimal complications and short
      hospitalization time, but it requires an experienced team of laparoscopic
      surgeons. The functional and oncological outcomes of LRP are expected to be
      improved as the medical team experience is extended.

PMID- 30183586
TI  - Laparoscopic Management in Morgagni Hernia - Short Series and Review of
      Literature.
AB  - Morgagni hernia occurs after a congenital retrosternal diaphragmatic defect; it
      is a rare form of diaphragmatic hernia (1-3% of cases). In general, this
      pathology is diagnosed in children; in adults it is frequently discovered in
      emergency or incidentally. Methods: We prospectively evaluated a series of 8
      patients admitted to First Surgical Clinic, St. Spiridon Hospital, Iasi during
      the period 2011-2017. Results: Out of 8 patients, 6 were operated on, one patient
      refusing surgery (followed periodically); the patient who was 91 years old had
      serious associated diseases that made surgery contraindicated. Symptomatology was
      nonspecific: in 5 cases Morgagni hernia was discovered during the exploration of
      an associated pathology, either with cardiopulmonary symptoms of dyspnea or
      palpitations. In 2 cases, the clinical aspect suggested an occlusive syndrome
      (the herniated organ is usually the transverse colon). The laparoscopic approach
      was used in all cases: two conversions were recorded due to the tight adherences
      of the herniated viscera (gastric, colon, epiplon). In 4 cases, the surgical cure
      of hernia was performed by suture and in 2 cases with prosthesis: dual mesh in
      one case and polypropylene mesh in another case. We did not register morbidity
      and the mean postoperative stay was 4 days (range 2-6 days). Conclusions: Hernia
      Morgagni betrays a rare pathology. The most common is asymptomatic but in
      complicated cases it is a cause of acute surgical abdomen. Surgical treatment is
      indicated even for asymptomatic cases due to serious complications Morgagni
      hernia may develop. The laparoscopic approach is ideal, as reduction of viscera
      in the abdomen is easy and the defect will be repaired by suturing or using a
      prosthesis, depending on its size.

PMID- 30183587
TI  - Staged Strategy for Early Abdominal Wall Closure in a Case Involving Ruptured
      Abdominal Aortic Aneurysm Requiring Open Abdomen in Which Primary Fascial Closure
      was Difficult to Achieve: A Case Report.
AB  - Open abdomen is sometimes necessary to save lives after ruptured abdominal aortic
      aneurysm repair. We report a case in which a staged strategy for early abdominal
      wall closure was applied to prevent the severe complications due to the extended
      period of open abdomen. An 81-year-old man with ruptured abdominal aortic
      aneurysm was transported to our hospital. After the first operation, which
      required open abdomen, prolonged visceral edema and retroperitoneal hematoma made
      primary fascial closure difficult. Mesh mediated fascial traction was undergone
      to reduce the gap in fascial dehiscence under negative pressure wound therapy.
      However, primary fascial closure could not be accomplished, and abdominal wall
      reconstruction was performed using bilateral anterior rectus abdominis sheath
      turnover flap method. Moreover, the skin along the abdominal wall was too tight
      to be closed primarily. Thus, a bipedicled skin flap was applied. The patient was
      transferred to another hospital without any remarkable complications. In the
      present case, the application of a staged closure strategy, which was based on
      the duration of open abdomenand the condition of the fascia and skin was
      considered to be important for achieving definitive abdominal closure and
      preventing the severe complications.

PMID- 30183588
TI  - Metastatic Breast Cancer to the Cervix Presenting with Abnormal Vaginal Bleeding
      During Chemotherapy: A Case Report and Literature Review.
AB  - The most common sites of invasive breast cancer metastasis are the lungs, liver,
      bones and brain. Less frequent sites include the gastrointestinal tract,
      pancreas, spleen, thyroid, adrenals, kidneys, heart and female genital tract. The
      uterus is reported as a rare site for metastasis, and even more so for an
      isolated metastasis. Other sites of extra-genital sources for uterine metastases
      include the colon, stomach, pancreas, gallbladder, lung, cutaneous melanoma,
      urinary bladder and thyroid. The rarity of breast cancer metastasis to the
      uterine cervix could be explained by the fact that the cervix has a small blood
      supply and an afferent lymph drainage system alone. It is rare to diagnose a
      cervical metastasis prior to eliciting the primary breast disease. Invasive
      lobular carcinoma metastasises to the female reproductive system more frequently
      than invasive ductal carcinoma. This paper presents a case of breast cancer
      metastasis to the cervix.

PMID- 30183589
TI  - A Rare Case of Intestinal Obstruction in an Elderly Woman.
AB  - Among intestinal obstruction, intussusception is one of the rare mechanical
      causes in the adult period. When it is met it present with abdominal pain,
      vomiting and other symptoms compatible with intestinal obstruction varying on the
      segments being involved. Compared to pediatric invagination which it is mostly
      idiopathic the adult form has an organic etiology causing a blurred
      symptomatology and needing advanced imaging diagnosis like computerized
      tomography. We present the case of a 70 year old woman with multiple Emergency
      Department presentations with abdominal pain and vomiting which received a clear
      diagnosis only the third time she came to hospital. Ultrasonography and plain
      abdominal x-ray were no specific and only the CT scan revealed the real cause of
      obstruction. Also conservative measures were useless the definitive treatment
      being surgery, the lesion necessitating enteral resection and end to end
      anastomosis. The pathology report revealed a benign tumor of proximal jejunum. In
      conclusion, adult intestinal invagination, although it is a rare condition, can
      present with symptomatology varying with segment of bowel involved into the
      intussusception. Unlike pediatric invagination, the adult one needs standard
      surgical revision unless there are certain contraindications.

PMID- 30183590
TI  - Jejunal Diverticulitis Mimicking Small Bowel Perforation: Case Report and Review
      of the Literature.
AB  - Jejunal diverticulitis is a rare entity with a higher prevalence among patients
      between 60 and 70 years. Jejunal diverticula are most often considered an
      incidental finding, but, they can have complications such as diverticulitis,
      perforation, abscess, generalized peritonitis, fistula, obstruction and
      bleeding.Setting the diagnosis still remains challenging. Physicians should be
      aware of their existence and the clinical suspicion should be raised, especially
      in the setting of acute abdominal pain where jejunal diverticulitis should be
      included in the differential diagnosis. A small amount of free air adjacent to
      the small bowel can be confusing and easily misdiagnosed as small bowel
      perforation, but, it can actually be found as a result of the inflammation itself
      without macroperforation or complications.This fact can change the therapeutic
      strategy to less aggressive, conservative treatments. We present a case of a
      patient coming to the emergency department with acute abdominal pain, signs of
      peritonitis, a small amount of extraluminal air, and jejunal diverticulitis
      without perforation was diagnosed on laparotomy, and a review of the current
      literature.

PMID- 30183591
TI  - The novel adipokine C1q-TNF related protein 9 (CTRP9) is elevated in systemic
      sclerosis-associated interstitial lung disease.

PMID- 30183592
TI  - Clinical implications of peripheral new bone formation in psoriatic arthritis: a
      literature-based review.
AB  - While the destructive changes of peripheral articular damage of psoriatic
      arthritis (PsA) are extensively studied, the productive modifications have been
      somewhat neglected. This literature-based study focuses on the clinically
      relevant aspects of peripheral bone proliferation in PsA. New bone proliferation
      frequently occurs as juxta-articular and entheseal apposition in PsA patients but
      also in psoriatic patients without arthritis, the Psoriatic Arthritis Ratingen
      Score is the only radiographic method to evaluate peri-articular new bone
      formation, numerous ultrasound systems to score entheseal changes have been
      proposed, several serum biomarkers of bone-turnover have been associated with PsA
      and psoriasis but they do not have clinical relevance. The effects of the
      biologics on peripheral new bone formation remains to be elucidated as well as
      the contribution of peripheral bone apposition to disability. Many aspects of
      peripheral osteoproliferation in PsA have not yet been properly addressed and
      represent clinical unmet needs of this rheumatic disorder.

PMID- 30183593
TI  - A prospective, longitudinal study evaluating the baseline six-minute walk test as
      an individual reference value in systemic sclerosis patients.
AB  - OBJECTIVES: Interstitial lung disease (ILD) and pulmonary arterial hypertension
      (PAH) are the leading causes of death in systemic sclerosis (SSc). Although the
      six-minute walk test (6MWT) is used for evaluating ILD and PAH, no data are
      available on the evolution of the six-minute walk distance (6MWD) in SSc patients
      without ILD and PAH and whether the baseline 6MWD could serve as individual
      reference value for the management of those who will develop PAH or ILD. METHODS:
      Prospectively collected data of the first 6MWT (at baseline or 6-month follow-up)
      and the 6MWTs at 18-, 30-, 42-, 54-, and 66-month visit of 165 consecutive SSc
      patients without ILD and PAH, included in the Ghent University SSc Cohort between
      May 2006 and December 2016 were analysed. RESULTS: 96-100% of the included
      patients performed a 6MWT during the follow-up visits. The mean 6MWD during the
      baseline 6MWT of 165 SSc patients without ILD and PAH (35% limited, 56% limited
      cutaneous, 9% diffuse cutaneous SSc) was 484.20+/-92.65m with no significant
      difference in the 6MWD at different follow-up visits as compared to baseline. In
      46 SSc patients without ILD and PAH who performed a 6MWT at baseline and at 66
      month visit, the 6MWD walked at 66-month visit correlated with the baseline 6MWD
      (r=0.564, p<0.001). CONCLUSIONS: In SSc without ILD and PAH, the 6MWT is feasible
      and the 6MWD is clinically stable over a 66 months period. Hence, the individual
      6MWD might be used as individual reference value in management of those who will
      develop PAH or ILD.

PMID- 30183594
TI  - Evaluation of extreme patient-reported outcome in early spondyloarthritis and its
      impact on the effect of TNF-alpha blockers treatment.
AB  - OBJECTIVES: To describe the prevalence of extreme patient-reported outcomes (PRO)
      in an early axial spondyloarthritis setting, to compare the phenotype of patients
      with/without extreme PRO and to evaluate the impact of extreme PRO on the
      effectiveness of TNF-alpha blockers (TNFb). METHODS: This analysis was performed
      in the DESIR cohort. Extreme PRO were measured at baseline and were defined as a
      score >=8 on at least three of first five BASDAI items. Phenotype of patient's
      with/without extreme PRO was compared. Impact of extreme PRO on TNFb
      effectiveness was evaluated by comparing the retention rate of the first TNFb in
      both groups by survival curves analysis (log-rank and Cox analysis). RESULTS:
      Extreme PRO were present in 95 out of the 708 patients (13.4%). Patients with
      extreme PRO were older (mean (SD) age of 35.4(8.6) years vs. 33.5(8.7) years),
      more frequently females (65.3% vs. 51.9%), had higher BASDAI (7.1 vs. 4.1),
      reported more frequently history of depression (25.3% vs. 10.2%) and use of anti
      depressive drugs (19.0% vs. 7.2%). TNFb treatment was more frequently initiated
      in the extreme PRO group (48.4% vs. 25.5%), while the proportion of patients
      still on TNFb at 2 years was significantly lower in the extreme PRO group 18.6%
      (n=8) vs. 39.5% (n=60). Presence of extreme PRO was independently associated with
      first TNFb discontinuation (HR 1.8, [95% CI 1.2;2.9], p=0.01)). CONCLUSIONS:
      Although presence of extreme PRO in this early axSpA setting was not very
      frequent, patients with extreme PRO were more likely to receive a TNFb and less
      likely to maintain the treatment at 2 years. Further studies evaluating the
      specific impact of extreme PRO on TNFb treatment in axSpA are warranted.

PMID- 30183596
TI  - Epidemiological, pharmacological and sociodemographic characterisation of a
      population of 386 fibromyalgic patients referred to a tertiary pain centre in
      Italy.
AB  - Fibromyalgia's prevalence in Italy is about 4%. Apart from widespread pain and
      the three main conditions related to fibromyalgia that are included in its
      diagnosis (fatigue, unrefreshing sleep and cognitive disorders disturbances),
      there are a number of minor symptoms that have been associated to fibromyalgia.
      The current study aimed to characterise fibromyalgic patients referring to a
      single tertiary pain centre not only for sociodemographic data, but also with
      special attention on pharmacological history and "minor" symptoms. "Minor" refers
      to the group of symptoms that were frequently associated and reported with
      fibromyalgia in various epidemiological studies but are not required for
      diagnosis. A retrospective analysis was made on 386 patients with confirmed
      diagnosis based on the 2010 modified criteria. Our results partially confirmed
      known sociodemographic data, but the prevalence of some "minor" symptoms are
      impressively high in our population.

PMID- 30183595
TI  - Efficacy and safety of certolizumab pegol in combination with methotrexate in
      methotrexate-inadequate responder Chinese patients with active rheumatoid
      arthritis: 24-week results from a randomised, double-blind, placebo-controlled
      phase 3 study.
AB  - OBJECTIVES: To evaluate the efficacy and safety of certolizumab pegol (CZP) in
      combination with methotrexate (MTX) in Chinese patients with active rheumatoid
      arthritis (RA) and an inadequate response to MTX. METHODS: This 24-week, phase 3,
      double-blind, placebo-controlled study was conducted in 30 centres across China.
      A total of 430 patients were randomised 3:1 to receive CZP 200 mg every 2 weeks
      (loading dose: 400 mg CZP at Weeks 0, 2 and 4) plus MTX or placebo (PBO) plus
      MTX. The primary endpoint was ACR20 response at Week 24, for which the
      superiority of CZP+MTX over PBO+MTX was evaluated. Additional parameters for
      clinical efficacy, health outcomes, immunogenicity and safety were assessed.
      RESULTS: At Week 24, 54.8% of CZP+MTX patients and 23.9% of PBO+MTX patients
      achieved ACR20 (odds ratio: 3.9, p<0.001). CZP+MTX patients also achieved greater
      improvements in HAQ-DI, higher ACR50/70 responses and higher DAS28(ESR) remission
      rate at Week 24. Rapid onset of response to CZP+MTX was observed as early as Week
      1 for most of the clinical, functional and patient-reported outcomes. Incidences
      of treatment-emergent adverse events (TEAEs) were similar between treatment arms.
      Serious TEAEs were reported by 6.3% of CZP+MTX patients and 2.7% of PBO+MTX
      patients. No new safety signals were observed. CONCLUSIONS: CZP in combination
      with MTX showed an acceptable safety profile, a rapid onset of response and
      sustained effects in reducing the signs and symptoms of RA and improving physical
      function in Chinese patients with RA and an inadequate response to MTX.

PMID- 30183597
TI  - Tocilizumab and the risk of respiratory adverse events in patients with
      rheumatoid arthritis: a systematic review and meta-analysis of randomised
      controlled trials.
AB  - OBJECTIVES: The purpose of this study is to evaluate the relative risk (RR) of
      respiratory adverse events (AEs) among patients with RA treated with TCZ.
      METHODS: Databases (PubMed, Embase and Cochrane Library) were searched for
      randomised controlled trials (RCT) comparing the use of TCZ with placebo (PBO) or
      active comparator agents in adults with RA published until October 28, 2017.
      Statistical analyses were conducted to calculate the RR of infectious and non
      infectious respiratory AEs and severe AEs (SAEs) using random-effects or fixed
      effects models based on the heterogeneity of the included studies. RESULTS: Eight
      trials were ultimately included. TCZ was associated with an increased risk of
      infectious respiratory AEs relative to comparator agents (RR 1.53, 95% confidence
      interval [95% CI] 1.04-2.25) but was not associated with an increased risk of non
      infectious respiratory AEs (RR 1.19, 95% CI 0.86-1.64). A subgroup analysis
      revealed similar results for non-infectious AEs and SAEs in the comparisons of
      TCZ with MTX and adalimumab (ADA), whereas increased risks of these AEs but not
      SAEs were observed compared with the PBO. CONCLUSIONS: Our meta-analysis did not
      reveal an increase in the risk of non-infectious respiratory AEs in adult
      patients with RA who were treated with TCZ compared with other csDMARDs and
      bDMARDs in RCTs.

PMID- 30183598
TI  - Altered mRNA expression levels of vaspin and adiponectin in peripheral blood
      mononuclear cells of systemic lupus erythematosus patients.
AB  - OBJECTIVES: Increasing studies have indicated the association between adipokines
      and multiple autoimmune diseases. This study aimed to evaluate the mRNA
      expression levels of vaspin, adiponectin and adrenomedullin in peripheral blood
      mononuclear cells (PBMCs) of patients with systemic lupus erythematosus (SLE), as
      well as their clinical associations. METHODS: A total of 46 SLE patients and 51
      normal controls were recruited. The three adipokines expression levels in PBMCs
      from SLE patients were measured by qRT-PCR, and their associations with major
      clinical and laboratory parameters of SLE patients were also analysed. RESULTS:
      Compared with normal controls, vaspin expression level in PBMCs was significantly
      decreased (p<0.001), whereas adiponectin expression level was significantly
      higher in SLE patients (p<0.001). There was no significant difference in
      adrenomedullin expression level between SLE patients and normal controls. Vaspin
      and adrenomedullin expression levels in more active SLE were significantly lower
      than those in less active SLE (p=0.012, p=0.046, respectively). No significant
      difference in these adipokine expression levels was observed between SLE patients
      with and without lupus nephritis (LN). There was also no significant association
      between mRNA levels of these adipokines and major clinical and laboratory
      parameters. CONCLUSIONS: Altered vaspin, adiponectin expression levels, and the
      associations between vaspin, adrenomedullin levels and disease activity in SLE
      patients suggested that these adipokines might play a role in SLE.

PMID- 30183599
TI  - From VEDOSS to established systemic sclerosis diagnosis according to ACR/EULAR
      2013 classification criteria: a French-Italian capillaroscopic survey.
AB  - OBJECTIVES: Nailfold capillaroscopy (NC) shows microcirculatory abnormalities in
      systemic sclerosis (SSc). The inclusion of NC specific abnormalities increases
      the sensitivity of both 2013 ACR/EULAR and VEDOSS (Very Early Diagnosis of
      Systemic Sclerosis) classification criteria. We aimed to detect NC features able
      to predict progression toward established SSc in VEDOSS patients. METHODS: Sixty
      six VEDOSS patients were enrolled. They had a clinical follow-up and underwent NC
      once a year, considering morphological parameters, appropriate pattern and semi-
      quantitative rating scale. RESULTS: In a mean follow-up time of 31 months, 21
      patients progressed into SSc (P = Progressors), while 45 were "Non Progressor"
      (NP). Comparing NC basal features of both groups, significantly larger loop
      diameter and apex width, higher haemorrhage and NC scores were found in P respect
      to NP patients. When comparing NC features of P patients who progressed within
      one year (FP = Fast progressor), loop diameter and apex width were significantly
      higher compared to all VEDOSS subjects. Each unit increase of apex width was
      associated with an increasing risk of 1% for developing SSc and the cut-off value
      of 103 MUm showed a positive predictive value of 56% and a negative predictive
      value of 71%. CONCLUSIONS: We describe NC findings in VEDOSS patients,
      identifying those suggesting a progression into established disease. These
      findings must be regarded as possible predictive risk factor to develop SSc and
      can also be of relevance in the detection of those cases with a faster
      development. Thus NC seems to have a diagnostic and prognostic role in VEDOSS
      cases.

PMID- 30183600
TI  - Validation of the Italian version of proposed GRAPPA flare questionnaire for
      patients with psoriatic arthritis.
AB  - OBJECTIVES: The aim of the present study was to validate an Italian version of
      the GRAPPA flare instrument to identify patients with psoriatic arthritis (PsA)
      with a possible disease flare. METHODS: This was a cross-sectional study
      enrolling consecutively PsA patients classified with CASPAR criteria. Inclusion
      criteria were: age >=18 years and stable treatment (at least six months of follow
      up) with conventional synthetic or biological DMARDs. The flare questionnaire was
      administered at baseline and within a two-week interval. Internal consistency of
      the questionnaire was evaluated with Cronbach's alpha coefficient. Construct
      validity of flare questionnaire was assessed using the correlation between flare
      score and disease activity indices, HAQ and serum C-reactive protein. Cohen's
      kappa was performed to assess the agreement level between the patient's
      perception of flare and the score of the questionnaire. Finally, test-retest was
      performed to assess the reliability of the instrument. RESULTS: 46 PsA patients
      were enrolled in this study. Of these, 30.4% reported a status of flare of their
      disease. The questionnaire was internally consistent (alpha=0.81). Moreover, the
      questionnaire score correlated with the main disease activity indices (Spearman
      Rho ranging from 0.30 to 0.66; p<0.01). The score of flare questionnaire showed a
      moderate agreement with the perception of flare from the patients (Cohen's
      kappa=0.54). Test-retest reliability showed a good intra-class correlation.
      CONCLUSIONS: This initial validation of the Italian version of the GRAPPA flare
      instrument was favourable. Our results confirm the utility of this questionnaire
      in the assessment of flare in PsA.

PMID- 30183601
TI  - Crystallising the role of adrenocorticotrophic hormone in the management of acute
      gout: a review.
AB  - OBJECTIVES: Acute gout is traditionally treated with NSAIDs, corticosteroids, and
      colchicine. However, the presence of comorbid conditions and advancing age, often
      seen in hospitalised patients, may prevent their use. We reviewed the published
      data on the use of ACTH in the treatment of acute gouty arthritis. METHODS: A
      search was performed up to June 2017. We included clinical trials or case
      studies/series where ACTH had been administered in human subjects as a treatment
      for acute gout or pseudogout. RESULTS: Data consistently demonstrated ACTH to be
      fast-acting, typically relieving the painful symptoms of acute gout within 24 h
      of treatment. Furthermore, the average number of days needed to achieve 100%
      resolution of gout symptoms in patients treated with ACTH was similar to those of
      the corticosteroid triamcinolone. Retrospective data confirm the efficacy of ACTH
      or the synthetic analogue Synacthen in the treatment of acute gout in patients
      with comorbidities such as cardiovascular disease, chronic kidney disease, and
      hypertension, including those who were hospitalised, with all patients responding
      after 1-3 doses. ACTH appears to be well-tolerated with side effects being minor
      and transient in nature. Importantly, ACTH/Synacthen has no clinically
      significant effect on glucose and potassium levels or blood pressure. Clinical
      evidence from available case studies supports these findings. CONCLUSIONS: ACTH
      is a fast acting, efficacious and well-tolerated option for patients with acute
      gout when traditional therapies have failed or are contraindicated. However,
      large, carefully designed, randomised controlled trials are required to confirm
      these findings.

PMID- 30183602
TI  - Rheum4U: Development and testing of a web-based tool for improving the quality of
      care for patients with rheumatoid arthritis.
AB  - OBJECTIVES: To develop a web-based tool (Rheum4U) to capture clinically
      meaningful data to direct treatment. Rheum4U integrates longitudinal clinical
      data capture of rheumatoid arthritis (RA) disease activity measures and patient
      reported outcomes measures (PROMs). This study tests the feasibility,
      acceptability and efficiency of Rheum4U among patients and healthcare providers.
      METHODS: Rheum4U was developed in two phases: P1 design and development; and P2
      pilot testing. P1: A working group of rheumatologists and researchers (n=13)
      performed a prioritisation exercise to determine data elements to be included in
      the platform. The specifications were finalised and supplied to the platform
      developer. Alpha testing was performed to correct initial software bugs. 18
      testers (physicians, nurses and recruited non-patient lay-testers) beta tested
      Rheum4U for usability. P2: Rheum4U was piloted in 2 rheumatology clinics and
      evaluated for feasibility, efficiency and acceptability using interviews,
      observation and questionnaires with patients and healthcare providers. RESULTS:
      110 RA patients, 9 rheumatologists and 9 allied health providers participated in
      the pilot. Mean patient age was 53 years and 74% were female. The majority (86%)
      were satisfied or very satisfied with online data entry and 79% preferred it to
      paper entry. Healthcare providers found Rheum4U easy and clear to use (90%), and
      they perceived that it improved their job performance (91%). Completeness and
      easy availability of the patient information improved clinic efficiency.
      CONCLUSIONS: Rheum4U highlights the benefits of a web-based tool for clinical
      care, quality improvement and research in the clinic and this study provides
      valuable information to inform full platform implementation.

PMID- 30183604
TI  - Associations between interleukin-10 gene polymorphisms and systemic lupus
      erythematosus risk: a meta-analysis with trial sequential analysis.
AB  - OBJECTIVES: Interleukin-10 (IL-10) polymorphisms have been reported to be
      associated with systemic lupus erythematosus (SLE), however, the results are
      controversial. Therefore, we conducted a meta-analysis with trial sequential
      analysis to evaluate a more accurate estimation of the associations. METHODS:
      Eligible studies were retrieved by searching PubMed, Embase, Google Scholar, VIP,
      Wan Fang and China National Knowledge Infrastructure databases. Hardy-Weinberg
      equilibrium (HWE) was evaluated. Odds ratios (ORs) and 95% confidence intervals
      (CIs) were calculated. Heterogeneity was evaluated by Q statistic and I2
      statistic. Sensitivity analysis and subgroup analysis (stratified by HWE, region,
      event sample size, source of controls, genotyping method) were conducted and the
      potential for publication bias was assessed. Trial sequential analysis was
      introduced to assess the information size and the positive results. RESULTS:
      Twenty case-control studies were included. Overall results from IL10-1082A/G
      polymorphism showed increased risk of systemic lupus erythematosus, but no
      significant associations were observed in both IL10-819C/T and IL10-592C/A
      polymorphism. Increased risk of SLE was also observed in IL10A/G polymorphism in
      Asian population, hospital-based and PCR-RFLP (polymerase chain reaction
      restriction fragment length polymorphism) subgroups. In addition, decreased risk
      of SLE was widely detected in IL10-819C/T and IL10-592C/A polymorphisms in
      subgroup analysis. CONCLUSIONS: Our study suggests that the IL10-1082A/G
      polymorphism is a risk factor in systemic lupus erythematosus. A decreased risk
      of SLE in the IL10-819C/T and IL10-592C/A polymorphisms in subgroups was also
      observed, but further rigorously studies are needed to confirm these results.

PMID- 30183603
TI  - Determinants of health-related quality of life in a multinational systemic
      sclerosis inception cohort.
AB  - OBJECTIVES: To evaluate health-related quality of life (HRQoL) and its
      determinants in a systemic sclerosis (SSc) multinational inception cohort. We
      performed a meta-analysis of data from individual countries, and compared the
      meta-analysis to individual country results by pooling data from each of the
      countries. METHODS: SSc patients within 2 years of disease onset were recruited
      from 5 countries participating in the International Systemic Sclerosis Inception
      Cohort (INSYNC). Data from each country's database were exported for analysis
      using a harmonised platform. HRQoL was assessed using the Medical Outcomes Short
      Form-36 (SF-36). Multivariate linear regression assessed associations between
      HRQoL and predictors in cohorts separately and meta-analyzed to generate pooled
      estimates. The analyses were repeated using individual patient data. RESULTS: Of
      the 637 SSc patients recruited, the majority was female (80.2%-83.3%), aged
      between 52.4-56.7 years with limited cutaneous disease subtype (48.6%-66.7%).
      HRQoL scores were lower for SSc patients than the general population (SF-36
      physical component summary (PCS) score (36.4-39.6), mental component summary
      (MCS) score (41.0-46.4)). Determinants of SF-36 PCS by meta-analysis included
      increasing age (beta=-0.1, 95%CI -0.2, -0.01), diffuse cutaneous disease subtype
      (beta=-8.4, 95%CI -10.6, -6.3), and pulmonary arterial hypertension (beta=-10.9,
      95%CI -16.6, -5.3). Increasing age (beta=0.09, 95%CI 0.0, 0.18) was the only
      variable associated with SF-36 MCS. Analyses using individual patient data
      revealed similar results to those of the meta-analysis of cohort data.
      CONCLUSIONS: Our study provides estimates of HRQoL in a large inception SSc
      cohort and provides evidence that individual patient data analysis is valid in
      the INSYNC dataset.

PMID- 30183605
TI  - Impact of a lung ultrasound course for rheumatology specialists (IMPACT-2).
AB  - OBJECTIVES: Lung ultrasound (LUS) plays an increasing role in diagnosis and
      monitoring of interstitial lung disease (ILD). Connective tissue disorders (CTD)
      frequently cause ILD, and often presents symptomatically after irreversible
      fibrosis has ensued. As point-of-care musculoskeletal ultrasound (US) is commonly
      utilised by rheumatologists, translating this US expertise towards LUS places the
      rheumatologist in a position to screen for ILD. However, a standardised
      curriculum for the rheumatology community is lacking. The aim of this study is to
      determine the effectiveness of a formalised lung US training course for
      rheumatologists. METHODS: Four rheumatology fellows and four board-certified
      rheumatologists participated in a 4-hour training session. Pre-course, post
      course and 6-month follow-up surveys evaluated perceptions towards previous US
      experience, training, clinical utility and attitudes toward lung US. Didactics
      explained the protocols utilised in ILD evaluation. Evaluation of knowledge in US
      physiology, lung anatomy, artifact and pathology recognition were done through
      written exams before, after training, and at 6 months and through a practical
      exam using live models and simulation. RESULTS: Temporally there was overall
      improvement in written test scores. Improvement was noted in overall practical
      skill score following training course (17.4% vs. 92.9%, p<0.001), in written test
      scores 49.3% vs. 72.5% p<0.001), and pathology identification (26.5% vs. 79.6%,
      p<0.001). Six-month follow assessments were similar to post-test results
      revealing similar written scores (70.6%) and practical scores (89.7%).
      CONCLUSIONS: This formalised lung ultrasound training course was effective in
      improving skills and knowledge of rheumatology specialists.

PMID- 30183606
TI  - Association between non-dipper hypertension and vitamin D deficiency in women
      with systemic lupus erythematosus.
AB  - OBJECTIVES: Blood pressure (BP) physiologically declines more than 10% at night.
      Subjects who do not experience this drop are classified as non-dippers. They have
      a higher risk of cardiovascular diseases (CVD). Vitamin D deficiency and non
      dipper pattern have been associated in the general population. Patients with
      systemic lupus erythematosus (SLE) are more likely to have vitamin D deficiency,
      a non-dipper pattern and CVD. We aimed to evaluate a possible relationship
      between vitamin D deficiency and non-dipper pattern in patients with SLE.
      METHODS: Using 24-hour ambulatory BP monitoring, 77 women with SLE were divided
      into dippers and non-dippers. 25-hydroxyvitamin D (25(OH)D) levels were compared
      between both groups. A multivariate analysis was used to determine which
      variables were independently associated with non-dipper pattern. RESULTS: 62% of
      patients were non-dippers. They had lower levels of 25(OH)D than dippers (19.4+/
      8.9 vs. 25.9+/-10.1 ng/ml, p=0.005). Patients with lower 25(OH)D levels were more
      likely to be non-dippers (OR 3.7, 95%CI 1.2-11.4; p=0.025). The nocturnal decline
      of mean BP correlated with levels of 25(OH)D (r=0.227, p=0.047). Night-time
      systolic, diastolic and mean BP inversely correlated with the levels of 25(OH)D
      (r=-0.274, p=0.016; r=-0.238, p=0.037, and r=-0.260, p=0.022, respectively), but
      only night- time systolic BP remained significant after adjustment for age and
      body mass index (r=-0.228, p=0.049). 25(OH)D levels and the use of mycophenolate
      were found to be independently associated with non-dipper pattern in SLE
      patients. CONCLUSIONS: Vitamin D deficiency may contribute to the development of
      a non-dipper pattern in patients with SLE.

PMID- 30183607
TI  - Real-world experience with tofacitinib for treatment of rheumatoid arthritis.
AB  - OBJECTIVES: Oral targeted synthetic disease-modifying anti-rheumatic drugs
      (DMARDs), including the Janus kinase inhibitors tofacitinib and baricitinib, are
      the latest addition to the therapeutic options for rheumatoid arthritis (RA).
      Tofacitinib 5 mg, twice daily, is approved for treatment, with or without
      methotrexate, of moderate to severe active RA in adults not adequately responding
      to, or not tolerating one or more DMARDs. In this narrative review we aimed to
      provide an overview of the real-world evidence for tofacitinib in RA. METHODS:
      The literature was reviewed up to March 2018 for studies regarding the efficacy
      and safety of tofacitinib for the treatment of RA. The focus was mainly on real
      world studies with implications for every day clinical practice. RESULTS: The
      efficacy and safety of tofacitinib have been comprehensively assessed in a wide
      programme of randomised controlled trials. Extensive observational research on
      tofacitinib in RA is also ongoing worldwide and a substantial body of post
      marketing real-world data from clinical practice is becoming available. There was
      a degree of consistency across the real-world studies reviewed. Tofacitinib tends
      to be used as monotherapy more frequently than bDMARDS and appears to be
      effective without background methotrexate. The data show a manageable safety
      profile, with no new safety signals and a discontinuation rate from safety issues
      <10%. Patients initiating tofacitinib usually have longer disease duration and
      have been exposed to longer bDMARDs than patients initiating a bDMARD.
      CONCLUSIONS: Real-world data are a key component of the evidence supporting the
      effectiveness of this novel drug and are of interest to all stakeholders.
      Treatment persistence and adherence to tofacitinib are good overall and similar
      to those seen for bDMARDs.

PMID- 30183608
TI  - Antineutrophil cytoplasmic antibody and/or antiglomerular basement membrane
      antibody associated crescentic glomerulonephritis in combination with IgG4
      related tubulointerstitial nephritis.
AB  - OBJECTIVES: Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is an immune
      mediated fibroinflammatory disorder and is characterised by elevated serum IgG4
      concentrations and dense lymphoplasmacytic infiltrate rich in IgG4+ plasma cells.
      IgG4-related tubulointerstitial nephritis (IgG4-TIN) is the most common
      manifestation of IgG4-related kidney disease (IgG4-RKD). We report four cases of
      kidney injury with concurrent IgG4-TIN and crescentic glomerulonephritis
      confirmed by renal pathology. METHODS: The medical charts of four patients were
      reviewed to collect clinical and laboratory data at the time of diagnosis,
      treatment and outcomes after 6-36 months. Two of them are cases of IgG4-TIN with
      antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), and the
      other two cases are rare IgG4-TIN with antiglomerular basement membrane (anti
      GBM) glomerulonephritis coexistent with ANCA-positive serum. RESULTS: Compared
      with IgG4-TIN, IgG4-TIN combined with AAV or anti-GBM glomerulonephritis is less
      associated with other organ injuries, and the clinical manifestations, treatment
      effects and prognosis were consistent with that of crescentic glomerulonephritis.
      CONCLUSIONS: IgG4-TIN concurrent with anti-GBM glomerulonephritis and positivity
      in serum has more severe clinical features and a worse renal prognosis than IgG4
      TIN coexistent with AVV.

PMID- 30183609
TI  - Does extent of prostate-specific antigen fluctuation can predict Gleason score
      upgrading in low-risk prostate cancer patients?
AB  - OBJECTIVE: To evaluate the effect of prostate-specific antigen (PSA) fluctuation
      on Gleason score (GS) upgrading, disease upstaging, oncological outcomes in low
      risk prostate cancer (PCa) patients who underwent robot-assisted laparoscopic
      radical prostatectomy (RARP) and met the inclusion criteria for active
      surveillance (AS). MATERIAL AND METHODS: Data of 354 low-risk PCa patients who
      underwent RARP were retrospectively evaluated. Patients were divided into two
      groups: PSA fluctuation rate<9.5%/month (Group 1, n=192) and >9.5%/month (Group
      2, n=162). Mainly compared parameters were GS upgrading, disease upstaging,
      biochemical recurrence (BCR) and surgical margin positivity (SMP) rates. RESULTS:
      GS upgrading, disease upstaging and SMP were detected in 128 (36.2%), 56 (15.8%)
      and 42 (11.9%) patients, respectively. After a median follow-up of 46 months, BCR
      was observed in 40 (11.3%) patients. GS upgrading (41.1% vs. 30.2%, p=0.033),
      disease upstaging (19.8% vs. 11.1%, p=0.028), SMP (15.1% vs. 8%, p=0.035) and BCR
      development (15.6% vs. 6.2%, p=0.005) rates were statistically significantly
      higher in Group 1 than Group 2. In multivariate analysis, digital rectal
      examination positivity, the presence of two positive cores and low PSA
      fluctuation rate were found to be significant predictors of GS upgrading.
      CONCLUSION: Low PSA fluctuation rate is associated with higher GS upgrading.

PMID- 30183610
TI  - Prognostic significance of tumor budding in muscle invasive urothelial carcinomas
      of the bladder.
AB  - OBJECTIVE: The aim of this study was to evaluate the prognostic significance of
      tumor budding in muscle invasive urothelial carcinoma of bladder (MIBC). MATERIAL
      AND METHODS: A total of 60 patients who underwent radical cystectomy and
      cystoprostatectomy for MIBC were included in the study. The correlations between
      tumor budding, and tumor necrosis, lymphovascular invasion (LVI), perineural
      invasion (PNI) and histopathological data with distant metastasis were evaluated.
      The correlation between progression free (PFS) and overall survival (OS) rates
      and the presence, and grade of tumor budding was investigated. RESULTS: A
      statistically significant correlation was not seen between tumor budding,
      necrosis, LVI, and PNI. There was a strong correlation between distant organ
      metastasis, and presence of tumor necrosis. There was no statistically
      significant correlation between PFS, OS and tumor budding. A statistically
      significant relationship was observed between OS and tumor stage, lymph node
      metastasis, and distant organ metastasis. CONCLUSION: In our study, statistically
      significant effect of tumor budding on survival rates in MIBCs was not observed.
      Also, no significant correlation was observed between tumor budding and tumor
      necrosis, LVI, and PNI.

PMID- 30183611
TI  - Scrotal ultrasonographic findings in obese infertile patients and their
      correlations to semen and hormonal profile.
AB  - OBJECTIVE: The aim of this prospective study was to compare scrotal
      ultrasonographic findings in obese and normal weight infertile men and correlate
      these findings with semen parameters and hormonal profile. MATERIAL AND METHODS:
      A total of 188 men presented for infertility evaluation were included in this
      study. They were divided according to body mass indices into obese (n=96) and
      normal weight infertile patients (n=92). Basic infertility evaluation, semen
      analysis and scrotal duplex ultrasound examination in addition to measurement of
      serum levels of follicular stimulating hormone, testosterone and estradiol were
      done for all cases. The ratio between testicular size measured by scrotal
      ultrasound and body mass index were calculated. RESULTS: Any significant
      differences were not observed in semen parameters, serum levels of follicular
      stimulating hormone and testosterone between obese and normal weight infertile
      men. Serum estradiol level was significantly higher in obese than normal weight
      infertile men. There is significant increase in subclinical varicocele, hydrocele
      and testicular microlithiasis detected by scrotal ultrasound in obese infertile
      men than nonobese patients. Despite having comparable testicular size detected on
      scrotal ultrasound, infertile obese men had significantly lower total testicular
      volume to body mass index ratio and this ratio correlated positively with semen
      volume, sperm concentration, total sperm count and serum testosterone but
      negatively with serum follicular stimulating hormone and estradiol levels.
      CONCLUSION: We therefore conclude that the incidence of subclinical varicocele,
      hydrocele and testicular microlithiasis was higher in obese infertile patients
      and the ratio between testicular volume assessed by scrotal ultrasound and body
      mass index may be a new parameter that correlates with subfertility status in
      these men.

PMID- 30183612
TI  - The effect of atorvastatin on penile intracavernosal pressure and cavernosal
      morphology in normocholesterolemic rats.
AB  - OBJECTIVE: A debate is open on the effects of lipid-lowering drugs on sexual
      function. We aimed to investigate the effect of atorvastatin use on penile
      intracavernosal pressure (ICP) and cavernosal morphology. MATERIAL AND METHODS:
      Fourteen mature male Sprague-Dawley-rats were randomly assigned to either the
      control group (which received standard food and water ad libitum) or the
      atorvastatin group (which received standard food, water, and statin) for twelwe
      weeks. At the end of the study, ICPs were measured with cavernosometry. Penectomy
      specimens were histologically examined. RESULTS: The following mean values were
      obtained for the control and atorvastatin groups, respectively: pre-study body
      weights (350+/-16.9 g and 331.4+/-24.9 g); post-study body weights (356+/-18 g
      and 368+/-22.5 g (p>0.05); ICPs at 5 V (5.96+/-5.16 mmHg and 2.11+/-1.22 mmHg
      (p=0.07)); ICPs at 10 V (18.28+/-14.1 mmHg and 5.56+/-5.58 mmHg) (p=0.09);
      testosterone (1.23+/-0.78 and 0.78+/-0.58 mmol/dL) (p=0.39); blood glucose (151+/
      22 mg/dL and 168.6+/-16.2 mg/dL) (p=0.12); triglyceride (93.4+/-19.8 mg/dL and
      52.1+/-18.6 mg/dL) (p=0.01); total cholesterol (50.2+/-7.2 mg/dL and 47.7+/-6.6
      mg/dL) (p=0.51); and low-density lipoprotein (LDL) cholesterol (10.0+/-4.4 mg/dL
      and 3.5+/-2.1 mg/dL) (p=0.01). The mean collagen thickness was similar (p=0.09);
      but the mean elastin thickness increased in the atorvastatin group (p=0.01).
      CONCLUSION: The present study showed that the use of atorvastatin reduced the
      intracavernosal pressure in 10 V stimulation, and minimally decreased
      testosterone levels in rats, within a short period of time. When statin treatment
      is considered for its protective properties on cardiovascular system or for its
      lipid-lowering effect. It should be kept in mind that atorvastatin may also
      adversely contribute to erectile dysfunction.

PMID- 30183613
TI  - Musculoskeletal involvement and ultrasonography update in systemic lupus
      erythematosus: New insights and review.
AB  - Ultrasonography has been rarely used to measure musculoskeletal and joint
      activity in systemic lupus erythematosus (SLE). The aim of this review is to
      discuss the utility and reliability of this non-invasive diagnostic tool for the
      assessment of joint disease in SLE patients. In the last decade, several reports
      have highlighted the role of ultrasonography for a better evaluation of SLE
      related musculoskeletal symptoms. The symptoms have also been associated with
      worse outcomes in SLE; therefore, it is essential to seek useful and accessible
      techniques for better understanding of such patients who are insufficiently
      assessed by standard physical examination.

PMID- 30183614
TI  - Blood safety policy: should cautionary policies be adopted with caution?

PMID- 30183616
TI  - Corrections for "Bioluminescence Tomography Based on Gaussian Weighted Laplace
      Prior Regularization for Morphological Imaging of Glioma".
AB  - In [1], the affiliation for Y. Gao, K. Wang and J. Tian should have appeared as
      follows:.

PMID- 30183617
TI  - Validation and use of a musculoskeletal gait model to study the role of
      functional electrical stimulation.
AB  - OBJECTIVE: Musculoskeletal modelling has been used to predict the effect of
      functional electrical stimulation (FES) on the mechanics of the musculoskeletal
      system. However, validation of the resulting muscle activations due to FES is
      challenging as conventional electromyography (EMG) recording of signals from the
      stimulated muscle is affected by stimulation artefacts. A validation approach
      using a combination of musculoskeletal modelling and EMG was proposed, whereby
      the effect on non-stimulated muscles is assessed using both techniques. The aim
      is to quantify the effect of FES on BFLH and validate this directly against EMG
      of gluteus maximus (GMAX). The hypotheses are that GMAX activation correlates
      with BFLH activation; and the muscle activation during FES gait can be predicted
      using musculoskeletal modelling. METHODS: Kinematics, kinetics and EMG of healthy
      subjects were measured under four walking conditions (normal walking followed by
      FES walking with three levels of BFLH stimulation). Measured kinematics and
      kinetics served as inputs to the musculoskeletal model. RESULTS: Strong positive
      correlations were found between GMAX activation and BFLH activation in early
      stance peak (R=0.78, p=0.002) and impulse (R=0.63, p=0.021). The modelled peak
      and impulse of GMAX activation increased with EMG peak ($p?lt0.001$) and impulse
      (p=0.021). CONCLUSION: Musculoskeletal modelling can be used reliably to quantify
      the effect of using FES on BFLH in a healthy gait activity. SIGNIFICANCE: The
      validation approach using EMG and musculoskeletal modelling developed and tested
      can potentially be applied to the use of FES for other muscles and activities.

PMID- 30183618
TI  - Response to "Ghost Numbers".
AB  - This note clarifies the experimental settings of [1] and shows that the issue
      raised by [2] is due to a lack of details in [1] which resulted in a
      misinterpretation of the experimental settings.

PMID- 30183619
TI  - Dense 3D Object Reconstruction from a Single Depth View.
AB  - In this paper, we propose a novel approach, 3D-RecGAN++, which reconstructs the
      complete 3D structure of a given object from a single arbitrary depth view using
      generative adversarial networks. Unlike existing work which typically requires
      multiple views of the same object or class labels to recover the full 3D
      geometry, the proposed 3D-RecGAN++ only takes the voxel grid representation of a
      depth view of the object as input, and is able to generate the complete 3D
      occupancy grid with a high resolution of $256^3$ by recovering the
      occluded/missing regions. The key idea is to combine the generative capabilities
      of 3D encoder-decoder and the conditional adversarial networks framework, to
      infer accurate and fine-grained 3D structures of objects in high-dimensional
      voxel space. Extensive experiments on large synthetic datasets and real-world
      Kinect datasets show that the proposed 3D-RecGAN++ significantly outperforms the
      state of the art in single view 3D object reconstruction, and is able to
      reconstruct unseen types of objects.

PMID- 30183615
TI  - Timing of the reticular lamina and basilar membrane vibration in living gerbil
      cochleae.
AB  - Auditory sensory outer hair cells are thought to amplify sound-induced basilar
      membrane vibration through a feedback mechanism to enhance hearing sensitivity.
      For optimal amplification, the outer hair cell-generated force must act on the
      basilar membrane at an appropriate time at every cycle. However, the temporal
      relationship between the outer hair cell-driven reticular lamina vibration and
      the basilar membrane vibration remains unclear. By measuring sub-nanometer
      vibrations directly from outer hair cells using a custom-built heterodyne low
      coherence interferometer, we demonstrate in living gerbil cochleae that the
      reticular lamina vibration occurs after, not before, the basilar membrane
      vibration. Both tone- and click-induced responses indicate that the reticular
      lamina and basilar membrane vibrate in opposite directions at the cochlear base
      and they oscillate in phase near the best-frequency location. Our results suggest
      that outer hair cells enhance hearing sensitivity through a global
      hydromechanical mechanism, rather than through a local mechanical feedback as
      commonly supposed.

PMID- 30183620
TI  - Representation Learning by Rotating Your Faces.
AB  - The large pose discrepancy between two face images is one of the fundamental
      challenges in automatic face recognition. Conventional approaches to pose
      invariant face recognition either perform face frontalization on, or learn a pose
      invariant representation from, a non-frontal face image. We argue that it is more
      desirable to perform both tasks jointly to allow them to leverage each other. To
      this end, this paper proposes a Disentangled Representation learning-Generative
      Adversarial Network (DR-GAN) with three distinct novelties. First, the encoder
      decoder structure of the generator enables DR-GAN to learn a representation that
      is both generative and discriminative, which can be used for face image synthesis
      and pose-invariant face recognition. Second, this representation is explicitly
      disentangled from other face variations such as pose, through the pose code
      provided to the decoder and pose estimation in the discriminator. Third, DR-GAN
      can take one or multiple images as the input, and generate one unified identity
      representation along with an arbitrary number of synthetic face images. Extensive
      quantitative and qualitative evaluation on a number of controlled and in-the-wild
      databases demonstrate the superiority of DR-GAN over the state of the art in both
      learning representations and rotating large-pose face images.

PMID- 30183621
TI  - Temporal Segment Networks for Action Recognition in Videos.
AB  - Deep convolutional networks have achieved great success for image recognition.
      However, for action recognition in videos, their advantage over traditional
      methods is not so evident. We present a general and flexible video-level
      framework for learning action models in videos. This method, called temporal
      segment network (TSN), aims to model long-range temporal structures with a new
      segment-based sampling and aggregation module. This unique design enables our TSN
      to efficiently learn action models by using the whole action videos. The learned
      models could be easily adapted for action recognition in both trimmed and
      untrimmed videos with simple average pooling and multi-scale temporal window
      integration, respectively. We also study a series of good practices for the
      instantiation of TSN framework given limited training samples. Our approach
      obtains the state-the-of-art performance on four challenging action recognition
      benchmarks: HMDB51 (71.0%), UCF101 (94.9%), THUMOS14 (80.1%), and ActivityNet
      v1.2 (89.6%). Using the proposed RGB difference for motion models, our method can
      still achieve competitive accuracy on UCF101 (91.0 %) while running at 340 FPS.
      Furthermore, based on the temporal segment networks, we won the video
      classification track at the ActivityNet challenge 2016 among 24 teams, which
      demonstrates the effectiveness of TSN and the proposed good practices.

PMID- 30183622
TI  - Dynamic Hyper-Graph Inference Framework for Computer Assisted Diagnosis of
      Neurodegenerative Diseases.
AB  - Hyper-graph techniques have been widely investigated in computer vision and
      medical imaging applications, showing superior performance for modeling complex
      subject-wise relationships and sufficient flexibility to deal with missing data
      from multi-modal neuroimaging data. Existing hyper-graph methods, however, are
      inadequate for two reasons. Firstly, representations are generated only from the
      observed imaging data, a process that is completely independent of the subsequent
      data label inference/classification step. Thus hyper-graph results constructed
      this way may not be consistent with phenotype data such as clinical labels or
      scores. More critically, it might generate sub-optimal predictions in relation to
      clinical labels/scores. Secondly, current hyper-graph inference methods rely on
      two sequential steps: 1) building the hyper-graph for each individual modality
      and then predicted latent labels for new subjects upon each constructed hyper
      graph, and 2) a voting procedure to incorporate inference results across
      different hyper-graphs. This approach, however, is limited by failing to consider
      the complex and complementary relationships of multi-modal imaging data with
      respect to hyper-graph inference procedure. To address these two issues, we
      propose a novel dynamic hyper-graph inference method supported by a semi
      supervised framework. Our method iteratively estimates and adjusts the hyper
      graph structures from multi-modal imaging data until consistency between the
      learned hyper-graph and the observed clinical labels and scores is achieved. This
      hyper-graph inference framework also eases the integration process of
      classification (identifying individuals having neurodegenerative disease) and
      regression (predicting the clinical scores) within the same framework. The
      experimental results on identifying MCI (Mild Cognition Impairment) subjects and
      the fine grained recognition of MCI progression stages show improved performance
      using our proposed hyper-graph inference method compared with conventional
      methods.

PMID- 30183623
TI  - An End-to-End Deep Learning Histochemical Scoring System for Breast Cancer TMA.
AB  - One of the methods for stratifying different molecular classes of breast cancer
      is the Nottingham Prognostic Index Plus (NPI+) which uses breast cancer relevant
      biomarkers to stain tumour tissues prepared on tissue microarray (TMA). To
      determine the molecular class of the tumour, pathologists will have to manually
      mark the nuclei activity biomarkers through a microscope and use a semi
      quantitative assessment method to assign a histochemical score (H-Score) to each
      TMA core. Manually marking positively stained nuclei is a time consuming,
      imprecise and subjective process which will lead to inter-observer and intra
      observer discrepancies. In this paper, we present an end-to-end deep learning
      system which directly predicts the H-Score automatically. Our system imitates the
      pathologists' decision process and uses one fully convolutional network (FCN) to
      extract all nuclei region (tumour and non-tumour), a second FCN to extract tumour
      nuclei region, and a multi-column convolutional neural network which takes the
      outputs of the first two FCNs and the stain intensity description image as input
      and acts as the high-level decision making mechanism to directly output the H
      Score of the input TMA image. To the best of our knowledge, this is the first end
      to-end system that takes a TMA image as input and directly outputs a clinical
      score. We will present experimental results which demonstrate that the H-Scores
      predicted by our model have very high and statistically significant correlation
      with experienced pathologists' scores and that the H-Score discrepancy between
      our algorithm and the pathologists is on par with the inter-subject discrepancy
      between the pathologists.

PMID- 30183624
TI  - Development of a KNN Ceramic-Based Lead-Free Linear Array Ultrasonic Transducer.
AB  - High-frequency array transducers can provide higher imaging resolution than
      traditional transducers, thus resolving smaller features and producing finer
      images. Commercially available ultrasonic transducers are mostly made with lead
      based piezoelectric materials, which are harmful to the environment and public
      health. This paper presents the development of the 64-elements high-frequency
      (18.3 MHz) lead-free linear array ultrasonic transducer based on
      (K0.44Na0.52Li0.04)(Nb0.86Ta0.1Sb0.04)O3 (KNLNTS) piezoceramic. Array elements
      were spaced at a 75- pitch, and interconnected via a custom flexible circuit. The
      two matching layers and a light backing material were used to improve the
      performance of the array. The developed KNLNTS ceramic-based lead-free linear
      array exhibited a center frequency of 18.3 MHz, an average -6-dB bandwidth of
      42%, an average two-way insertion loss of 41.8 dB, and a crosstalk between the
      adjacent elements of less than -53 dB near the center frequency. An image of a
      tungsten wire phantom was acquired using a Verasonics Vantage research ultrasound
      system. Results from imaging tests demonstrated a good imaging capability with a
      spatial resolution of axially and laterally, indicating that the lead-free linear
      array ultrasonic transducer based on KNLNTS ceramics is a promising alternative
      to lead-based transducers for ultrasound medical imaging.

PMID- 30183625
TI  - Multidimensional Clutter Filter Optimization for Ultrasonic Perfusion Imaging.
AB  - Combinations of novel pulse-echo acquisitions and clutter filtering techniques
      can improve the sensitivity and the specificity of power Doppler (PD) images,
      thus reducing the need for exogenous contrast enhancement. We acquire echoes
      following bursts of Doppler pulse transmissions sparsely applied in regular
      patterns over long durations. The goal is to increase the sensitivity of the
      acquisition to slow disorganized patterns of motion from the peripheral blood
      perfusion. To counter a concomitant increase in clutter signal power, we arrange
      the temporal echo acquisitions into two data-array axes, combine them with a
      spatial axis for the tissue region of interest, and apply 3-D singular-value
      decomposition (SVD) clutter filtering. Successful separation of blood echoes from
      other echo signal sources requires that we partition the 3-D SVD core tensor.
      Unfortunately, the clutter and blood subspaces do not completely uncouple in all
      situations, so we developed a statistical classifier that identifies the core
      tensor subspace dominated by tissue clutter power. This paper describes an
      approach to subspace partitioning as required for optimizing PD imaging of
      peripheral perfusion. The technique is validated using echo simulation, flow
      phantom data, and in vivo data from a murine melanoma model. We find that for
      narrow eigen-bandwidth clutter signals, we can routinely map phantom flows and
      tumor perfusion signals at speeds less than 3 mL/min. The proposed method is well
      suited to peripheral perfusion imaging applications.

PMID- 30183626
TI  - Temporal Colored Coded Aperture Design in Compressive Spectral Video Sensing.
AB  - Compressive spectral video sensing (CSVS) systems obtain spatial, spectral, and
      temporal information of a dynamic scene through the encoding of the incoming
      light rays by using a temporal-static coded aperture (CA). CSVS systems use CAs
      with binary entries spatially distributed at random. The random spatial encoding
      of the binary CAs entails a poor quality in the reconstructed images even though
      the CSVS sensing matrix is incoherent with the sparse representation basis. In
      addition, since some pixels are totally blocked, information such as object
      motion is missed over time. This paper substitutes the temporal-static binary
      coded apertures by a richer spatio-spectro-temporal encoding based on selectable
      color filters, named temporal colored coded apertures (T-CCA). The spatial,
      spectral, and time distributions of the T-CCAs are optimized by better satisfying
      the restricted isometry property (RIP) of the CSVS system. The RIP-optimized T
      CCAs lead to spatio-spectral-time structures that tend to sense more uniformly
      the spatial, spectral, and temporal dimensions. An algorithm for optimally
      designing the T-CCAs is developed. In addition, a regularization term based on
      the scene motion is included in the inverse problem leading to a better quality
      of the reconstructed images. Computational experiments using four different
      spectral videos show an improvement of up to 6 dB in terms of peak signal-to
      noise ratio of the reconstructed images by using the proposed inverse problem and
      the T-CCA patterns compared with the binary CAs and random and image-optimized
      CCA patterns.

PMID- 30183627
TI  - Multi-Resolution Compressive Spectral Imaging Reconstruction from Single Pixel
      Measurements.
AB  - Massive amounts of data in spectral imagery increase acquisition, storing and
      processing costs. Compressive spectral imaging (CSI) methods allow the
      reconstruction of spatial and spectral information from a small set of random
      projections. The single pixel camera is a low cost optical architecture which
      enables the compressive acquisition of spectral images. Traditional CSI
      reconstruction methods obtain a sparse approximation of the underlying spatial
      and spectral information, however the complexity of these algorithms increases in
      proportion to the dimensionality of the data. This work proposes a
      multiresolution (MR) CSI reconstruction approach from single pixel camera
      measurements that exploits spectral similarities between pixels to group them in
      super-pixels such that the total number of unknowns in the inverse problem is
      reduced. Specifically, two different types of super-pixels are considered:
      rectangular and irregular structures. Simulation and experimental results show
      that the proposed MR scheme improves reconstruction quality in up to 6dB of PSNR
      and reconstruction time in up to 90% with respect to the traditional full
      resolution reconstructions.

PMID- 30183628
TI  - Probabilistic Diffusion for Interactive Image Segmentation.
AB  - This paper presents an interactive image segmentation approach in which we
      formulate segmentation as a probabilistic estimation problem based on the prior
      user intention. Instead of directly measuring the relationship between pixels and
      labels, we first estimate the distances between pixel pairs and label pairs using
      a probabilistic framework. Then, binary probabilities with label pairs are
      naturally converted to unary probabilities with labels. The higher order
      relationship helps improve the robustness to user inputs. To improve segmentation
      accuracy, a likelihood learning framework is proposed to fuse the region and the
      boundary information of the image by imposing a smoothing constraint on the unary
      potentials. Furthermore, we establish an equivalence relationship between
      likelihood learning and likelihood diffusion and propose an iterative diffusion
      based optimization strategy to maintain computational efficiency. Experiments on
      the Berkeley segmentation data set and Microsoft GrabCut database demonstrate
      that the proposed method can obtain better performance than the state-of-the-art
      methods.

PMID- 30183629
TI  - A Bayesian framework for the analog reconstruction of kymographs from
      fluorescence microscopy data.
AB  - Kymographs are widely used to represent and analyse spatio-temporal dynamics of
      fluorescence markers along curvilinear biological compartments. These objects
      have a singular geometry, thus kymograph reconstruction is inherently an analog
      image processing task. However, the existing approaches are essentially digital:
      the kymograph photometry is sampled directly from the time-lapse images. As a
      result, such kymographs rely on raw image data that suffer from the degradations
      entailed by the image formation process and the spatio-temporal resolution of the
      imaging setup. In this work, we address these limitations and introduce a well
      grounded Bayesian framework for the analog reconstruction of kymographs. To
      handle the movement of the object, we introduce an intrinsic description of
      kymographs using differential geometry: a kymograph is a photometry defined on a
      parameter space that is embedded in physical space by a time-varying map that
      follows the object geometry. We model the kymograph photometry as a Levy
      innovation process, a flexible class of non-parametric signal priors. We account
      for the image formation process using the virtual microscope framework. We
      formulate a computationally tractable representation of the associated maximum a
      posteriori problem and solve it using a class of efficient and modular algorithms
      based on the alternating split Bregman. We assess the performance of our Bayesian
      framework on synthetic data and apply it to reconstruct the fluorescence dynamics
      along microtubules in vivo in the budding yeast S. cerevisiae. We demonstrate
      that our framework allows revealing patterns from single time-lapse data that are
      invisible on standard digital kymographs.

PMID- 30183630
TI  - Similarity Domains Machine for Scale-Invariant and Sparse Shape Modeling.
AB  - We present an approach to extend the functionality and the use of kernel machines
      in image processing applications. We introduce a novel way to design spatial
      kernel machines with spatial properties and demonstrate how those newly
      introduced spatial properties enhance the possibilities of the use of kernel
      machines in image processing applications as a proof of concept. In this paper,
      we demonstrate four particular extensions: 1) how to model shapes efficiently
      with spatially computed kernel parameters in a geometrically scalable way; 2) how
      to visualize the kernel parameters precisely and intuitively on binary 2D shapes;
      3) how to construct a one-class classifier from the binary classifier in a
      straightforward manner without re-training; and 4) how to use the computed kernel
      parameters for filtering. The existing literature on kernel machines mostly
      focuses on estimating the optimal kernel parameters via additional cost
      function(s). In this paper, instead of employing an additional cost function to
      estimate the kernel-related parameters, we investigate on an analytical solution
      to predict the actual kernel parameters locally and show how to build a spatial
      kernel machine with our analytical approach. Classical kernel machines do not
      perform well on precise shape modeling with a low number of support vectors as
      demonstrated in this paper. However, we demonstrate and visualize that our
      analytical approach provides a natural means to relate the kernel parameters to
      the 2D shapes for sparse shape modeling, where the shape boundary represents the
      decision boundary. For that, we incorporate the selected kernel function's
      geometric properties as an additional constraint into the classifier's
      optimization problem by defining an easy-to-explain and intuitive concept:
      similarity domains. In our experiments, we study and demonstrate how the
      resulting new kernel machine enhances the capabilities of the classical kernel
      machines with applications on shape modeling, (geometrically) scaling the non
      linear decision boundary at various scales and precise visualization of the
      kernel parameters in 2D images.

PMID- 30183631
TI  - Reliable Crowdsourcing and Deep Locality-Preserving Learning for Unconstrained
      Facial Expression Recognition.
AB  - Facial expression is central to human experience, but most previous databases and
      studies are limited to posed facial behavior under controlled conditions. In this
      paper, we present a novel facial expression database, Real-world Affective Face
      Database (RAF-DB), which contains approximately 30 000 facial images with
      uncontrolled poses and illumination from thousands of individuals of diverse ages
      and races. During the crowdsourcing annotation, each image is independently
      labeled by approximately 40 annotators. An expectation-maximization algorithm is
      developed to reliably estimate the emotion labels, which reveals that real-world
      faces often express compound or even mixture emotions. A cross-database study
      between RAF-DB and CK+ database further indicates that the action units of real
      world emotions are much more diverse than, or even deviate from, those of
      laboratory-controlled emotions. To address the recognition of multi-modal
      expressions in the wild, we propose a new deep locality-preserving convolutional
      neural network (DLP-CNN) method that aims to enhance the discriminative power of
      deep features by preserving the locality closeness while maximizing the inter
      class scatter. Benchmark experiments on 7-class basic expressions and 11-class
      compound expressions, as well as additional experiments on CK+, MMI, and SFEW 2.0
      databases, show that the proposed DLP-CNN outperforms the state-of-the-art
      handcrafted features and deep learning-based methods for expression recognition
      in the wild. To promote further study, we have made the RAF database, benchmarks,
      and descriptor encodings publicly available to the research community.

PMID- 30183632
TI  - Accurate Modelling and Efficient Estimation of the Print-Capture Channel with
      Application in Barcoding.
AB  - With the rapid advancement of sensing capability and computational power in
      consumer electronic devices, the use of mobile cameras for communications has
      attracted significant attention from both academia and industry. The design of a
      reliable communication system over the print-capture channel is a key challenge
      in some important applications, such as barcoding and document authentication.
      However, the real-world printcapture channel is spatially non-linear and non
      stationary, and lacks a standard parametric model. As a consequence, advanced
      channel coding techniques developed for common channel models are not applicable
      in the existing systems without costly and device-dependent pre-training. In this
      work, an accurate parametric print-capture channel model and an efficient channel
      estimation scheme requiring low training overhead are proposed. With the
      estimated parameters, the proposed print-capture channel model can be linearized
      to the (possibly input-dependent) additive white Gaussian noise (AWGN) channel
      model. This allows the use of state-of-the-art channel coding schemes, such as
      low-density parity-check (LDPC) codes with iterative soft decoding, to improve
      the reliability of the communication system under challenging conditions, e.g.,
      at a low signal-to-noise ratio. As an example application of the proposed print
      capture channel model, a demonstrative multilevel 2D barcode using an LDPC code
      with iterative soft decoding, is designed to enhance the reliability over the
      conventional QR code which is based on the Reed-Solomon code with hard decoding.
      At a printing resolution of 600dpi, the 8-level 2D barcode achieves data capacity
      gains of about 10% and 56% over the QR code in the in-focus and blurlimited
      scenarios, respectively. It is noteworthy that the enhanced data capacity of the
      multilevel barcode is made possible by the proposed channel estimation scheme,
      which incurs an additional training overhead of about 3.3% only.

PMID- 30183633
TI  - Secure Quaternion Feistel Cipher for DICOM Images.
AB  - An improved and extended version of a quaternion-based lossless encryption
      technique for digital image and communication on medicine (DICOM) images is
      proposed. We highlight and address several security flaws present in the previous
      version of the algorithm originally proposed by Dzwonkowski et al. (2015). The
      newly proposed secure quaternion Feistel cipher (S-QFC) algorithm retains the
      concept of a modified Feistel network with modular arithmetic and the use of
      special properties of quaternions to perform rotations of data sequences in 3D
      space for each of the cipher rounds. A new and more secure key generation scheme
      based on quaternion Julia sets is utilized. We also introduce both-sided modular
      matrix multiplications for the encryption and decryption processes. The proposed
      S-QFC algorithm eliminates the major security flaws of its predecessor while
      maintaining high computation speed in comparison to other algorithms originally
      embedded in DICOM (i.e., advanced encryption standard and triple data encryption
      standard). A computer-based analysis has been carried out. Simulation results and
      cryptanalysis are shown at the end of this paper.

PMID- 30183634
TI  - SeqViews2SeqLabels: Learning 3D Global Features via Aggregating Sequential Views
      by RNN With Attention.
AB  - Learning 3D global features by aggregating multiple views has been introduced as
      a successful strategy for 3D shape analysis. In recent deep learning models with
      end-to-end training, pooling is a widely adopted procedure for view aggregation.
      However, pooling merely retains the max or mean value over all views, which
      disregards the content information of almost all views and also the spatial
      information among the views. To resolve these issues, we propose Sequential Views
      To Sequential Labels (SeqViews2SeqLabels) as a novel deep learning model with an
      encoder-decoder structure based on recurrent neural networks (RNNs) with
      attention. SeqViews2SeqLabels consists of two connected parts, an encoder-RNN
      followed by a decoder-RNN, that aim to learn the global features by aggregating
      sequential views and then performing shape classification from the learned global
      features, respectively. Specifically, the encoder-RNN learns the global features
      by simultaneously encoding the spatial and content information of sequential
      views, which captures the semantics of the view sequence. With the proposed
      prediction of sequential labels, the decoder-RNN performs more accurate
      classification using the learned global features by predicting sequential labels
      step by step. Learning to predict sequential labels provides more and finer
      discriminative information among shape classes to learn, which alleviates the
      overfitting problem inherent in training using a limited number of 3D shapes.
      Moreover, we introduce an attention mechanism to further improve the
      discriminative ability of SeqViews2SeqLabels. This mechanism increases the weight
      of views that are distinctive to each shape class, and it dramatically reduces
      the effect of selecting the first view position. Shape classification and
      retrieval results under three large-scale benchmarks verify that
      SeqViews2SeqLabels learns more discriminative global features by more effectively
      aggregating sequential views than state-of-the-art methods.

PMID- 30183635
TI  - Robust and Fast Extraction of 3D Symmetric Tensor Field Topology.
AB  - 3D symmetric tensor fields appear in many science and engineering fields, and
      topology-driven analysis is important in many of these application domains, such
      as solid mechanics and fluid dynamics. Degenerate curves and neutral surfaces are
      important topological features in 3D symmetric tensor fields. Existing methods to
      extract degenerate curves and neutral surfaces often miss parts of the curves and
      surfaces, respectively. Moreover, these methods are computationally expensive due
      to the lack of knowledge of structures of degenerate curves and neutral surfaces.
      In this paper, we provide theoretical analysis on the geometric and topological
      structures of degenerate curves and neutral surfaces of 3D linear tensor fields.
      These structures lead to parameterizations for degenerate curves and neutral
      surfaces that can not only provide more robust extraction of these features but
      also incur less computational cost. We demonstrate the benefits of our approach
      by applying our degenerate curve and neutral surface detection techniques to
      solid mechanics simulation data sets.

PMID- 30183636
TI  - Identification of Temporally Varying Areas of Interest in Long-Duration Eye
      Tracking Data Sets.
AB  - Eye-tracking has become an invaluable tool for the analysis of working practices
      in many technological fields of activity. Typically studies focus on short tasks
      and use static expected areas of interest (AoI) in the display to explore
      subjects' behaviour, making the analyst's task quite straightforward. In long
      duration studies, where the observations may last several hours over a complete
      work session, the AoIs may change over time in response to altering workload,
      emergencies or other variables making the analysis more difficult. This work puts
      forward a novel method to automatically identify spatial AoIs changing over time
      through a combination of clustering and cluster merging in the temporal domain. A
      visual analysis system based on the proposed methods is also presented. Finally,
      we illustrate our approach within the domain of air traffic control, a complex
      task sensitive to prevailing conditions over long durations, though it is
      applicable to other domains such as monitoring of complex systems.

PMID- 30183637
TI  - Feature Level-Sets: Generalizing Iso-surfaces to Multi-variate Data.
AB  - Iso-surfaces or level-sets provide an effective and frequently used means for
      feature visualization. However, they are restricted to simple features for uni
      variate data. The approach does not scale when moving to multi-variate data or
      when considering more complex feature definitions. In this paper, we introduce
      the concept of traits and feature level-sets, which can be understood as a
      generalization of level-sets as it includes iso-surfaces, and fiber surfaces as
      special cases. The concept is applicable to a large class of traits defined as
      subsets in attribute space, which can be arbitrary combinations of points, lines,
      surfaces and volumes. It is implemented into a system that provides an interface
      to define traits in an interactive way and multiple rendering options. We
      demonstrate the effectiveness of the approach using multi-variate data sets of
      different nature, including vector and tensor data, from different application
      domains.

PMID- 30183638
TI  - Beta event-related desynchronization can be enhanced by different training
      programs and is correlated with improved postural control in individuals with
      Parkinson's disease.
AB  - BACKGROUND AND OBJECTIVE: The purpose of this study was to investigate the
      effects of a specific exercise (SE) training program focusing on balance and
      muscle strengthening and a turning-based treadmill (TT) training program on
      cortical desynchronization and postural control in Parkinson's disease (PD).
      METHODS: Eighteen patients with PD were recruited and randomly assigned to the SE
      group, TT training group or control exercise (CE) group and participated in 12 30
      min training sessions focusing on balance and strengthening, turning-based
      treadmill training, or general exercise training, respectively, followed by 10
      minutes of over-ground walking in each session for 4 to 6 weeks. The outcomes
      included alpha event-related desynchronization (ERD), beta ERD, postural control
      ability indicated by postural instability and gait disorder (PIGD), the
      step/quick turn test (SQT), and the sensory organization test (SOT). All
      measurements were assessed at baseline and after training. RESULTS: The results
      (n=6 for each group) showed that both the SE and TT groups had improved beta ERD,
      but not alpha ERD, in the Cz area, PIGD score, and turn sway/time in the SQT
      compared with the CE group. Furthermore, postural control ability was positively
      correlated with beta ERD in the Cz area. However, there was no significant
      correlation between SOT total score and alpha ERD in the Cz area. CONCLUSIONS:
      This study showed that beta ERD in the central area and postural control can be
      improved with balance training, along with lower extremity muscle strengthening
      exercise and turning-based treadmill training, in patients with PD. Furthermore,
      improvement in beta ERD in the central area correlated with improvements in
      postural control ability. This trial was registered at http://www.anzctr.org.au/
      (ACTRN12616000198426).

PMID- 30183639
TI  - Probe Efficient Feature Representation of Gapped K-mer Frequency Vectors from
      Sequences using Deep Neural Networks.
AB  - Gapped k-mers frequency vectors (gkm-fv) has been presented for extracting
      sequence features. Coupled with support vector machine (gkm-SVM), gkm-fvs have
      been used to achieve effective sequence-based predictions. However, the huge
      computation of a large kernel matrix prevents it from using large amount of data.
      And it is unclear how to combine gkm-fvs with other data sources in the context
      of string kernel. On the other hand, the high dimensionality, colinearity and
      sparsity of gkm-fvs hinder the use of many traditional machine learning methods
      without a kernel trick. Therefore, we proposed a flexible and scalable framework
      gkm-DNN to achieve feature representation from high-dimensional gkm-fvs using
      deep neural networks (DNN). We first proposed a more concise version of gkm-fvs,
      which significantly reduce the dimension of gkm-fvs. Then we implemented an
      efficient method to calculate the gkm-fv of a given sequence at the first time.
      Finally, we adopted a DNN model with gkm-fvs as inputs to achieve efficient
      feature representation and a prediction task. Here, we took the transcription
      factor binding site prediction as an illustrative application and applied gkm-DNN
      onto 467 small and 69 big human ENCODE ChIP-seq datasets to demonstrate its
      performance and compared it with the state-of-the-art method gkm-SVM.

PMID- 30183640
TI  - Extracting Biomedical Events with Parallel Multi-Pooling Convolutional Neural
      Networks.
AB  - Biomedical event extraction is important for medical research and disease
      prevention, which has attracted much attention in recent years. Traditionally,
      most of the state-of-the-art systems have been based on shallow machine learning
      methods, which require many complex, hand-designed features. In addition, the
      words encoded by one-hot are unable to represent semantic information. Therefore,
      we utilize dependency-based embeddings to represent words semantically and
      syntactically. Then, we propose a parallel multi-pooling convolutional neural
      network (PMCNN) model to capture the compositional semantic features of
      sentences. Furthermore, we employ a rectified linear unit, which creates sparse
      representations with true zeros, and which is adapted to the biomedical event
      extraction, as a nonlinear function in PMCNN architecture. The experimental
      results from MLEE dataset show that our approach achieves an F1 score of 80.27%
      in trigger identification and an F1 score of 59.65% in biomedical event
      extraction, which performs better than other state-of-the-art methods.

PMID- 30183641
TI  - Parallel Protein Community Detection in Large-scale PPI Networks Based on Multi
      source Learning.
AB  - Protein interactions constitute the fundamental building block of almost every
      life activity. Identifying protein communities from Protein-Protein Interaction
      (PPI) networks is essential to understand the principles of cellular organization
      and explore the causes of various diseases. It is critical to integrate multiple
      data resources to identify reliable protein communities that have biological
      significance and improve the performance of community detection methods for large
      scale PPI networks. In this paper, we propose a Multi-source Learning based
      Protein Community Detection (MLPCD) algorithm by integrating Gene Expression Data
      (GED) and a parallel solution of MLPCD using cloud computing technology. GED
      under different conditions is integrated with the original PPI network to
      reconstruct a Weighted-PPI network. To flexibly identify protein communities of
      different scales, we define community modularity and functional cohesion
      measurements and detect protein communities from WPPI. In addition, we compare
      the detected communities with known protein complexes and evaluate the function
      enrichment of protein functional modules using Gene Ontology annotations. We
      implement a parallel version of MLPCD on the Apache Spark platform to enhance the
      performance of the algorithm. Extensive experimental results indicate the
      superiority and notable advantages of the MLPCD algorithm over the relevant
      algorithms in terms of accuracy and performance.

PMID- 30183642
TI  - Classification of a DNA Microarray for Diagnosing Cancer Using a Complex Network
      Based Method.
AB  - Applications that classify DNA microarray expression data are helpful for
      diagnosing cancer. Many attempts have been made to analyze these data; however,
      new methods are needed to obtain better results. In this study, a Complex Network
      (CN) classifier was exploited to implement the classification task. An algorithm
      was used to initialize the structure, which allowed input variables to be
      selected over layered connections and different activation functions for
      different nodes. Then, a hybrid method integrated the Genetic Programming and the
      Particle Swarm Optimization algorithms was used to identify an optimal structure
      with the parameters encoded in the classifier. The single CN classifier and an
      ensemble of CN classifiers were tested on four bench data sets. To ensure
      diversity of the ensemble classifiers, we constructed a base classifier using
      different feature sets, i.e., Pearson's correlation, Spearman's correlation,
      Euclidean distance, Cosine coefficient and the Fisher-ratio. The experimental
      results suggest that a single classifier can be used to obtain state-of-the-art
      results and the ensemble yielded better results.

PMID- 30183643
TI  - Integrating Language Model and Reading Control Gate in BLSTM-CRF for Biomedical
      Named Entity Recognition.
AB  - Biomedical named entity recognition (Bio-NER) is an important preliminary step
      for many biomedical text mining tasks. The current mainstream methods for NER are
      based on the neural networks to avoid the complex hand-designed features derived
      from various linguistic analyses. However, these methods ignore some potential
      sentence-level semantic information and general features of semantic and
      syntactic. Therefore, we propose a novel Long Short Term Memory (LSTM) Networks
      model integrating language model and sentence-level reading control gate (LS
      BLSTM-CRF) for Bio-NER. In our model, a sentence-level reading control gate (SC)
      is inserted into the networks to integrate the implicit meaning of an entire
      sentence and the language model is integrated to our model to learn richer
      potential features. Besides, character-level embeddings are introduced as the
      input to deal with out-of-vocabulary words. The experimental results conducted on
      the BioCreative II GM corpus show that our method can achieve an F-score of
      89.94%, which outperforms all state-of-the-art systems and is 1.33% higher than
      the best performing neural networks.

PMID- 30183644
TI  - WeCoMXP: Weighted Connectivity Measure Integrating Co-Methylation, Co-Expression
      and Protein-Protein Interactions for Gene-Module Detection.
AB  - The identification of modules (groups of several tightly interconnected genes) in
      gene interaction network is an essential task for better understanding of the
      architecture of the whole network. In this article, we develop a novel weighted
      connectivity measure integrating co-methylation, co-expression and protein
      protein interactions (called WeCoMXP) to detect gene-modules for multi-omics
      dataset. The proposed measure goes beyond the fundamental degree centrality
      measure through considering some formulation of higher-order connections.
      Thereafter, we apply the average linkage clustering method using the
      corresponding dissimilarity (distance) values of WeCoMXP scores, and utilize a
      dynamic tree cut method for identifying some gene-modules. We validate the
      modules through literature search, KEGG pathway, and gene-ontology analyses on
      the genes representing the modules. Furthermore, the top ten TFs/miRNAs that are
      connected with the maximum number of gene-modules and that regulate/target the
      maximum number of genes from these connected gene-modules, are identified.
      Moreover, our proposed method provides a better performance than the existing
      methods in terms of several cluster-validity indices in maximum times.

PMID- 30183645
TI  - Utilising Deep Learning and Genome Wide Association Studies for Epistatic-Driven
      Preterm Birth Classification in African-American Women.
AB  - Genome-Wide Association Studies (GWAS) are used to identify statistically
      significant genetic variants in case-control studies. The main objective is to
      find single nucleotide polymorphisms (SNPs) that influence a particular
      phenotype. GWAS use a p-value threshold of $5?star 10^{-8}$ to identify highly
      ranked SNPs. While this approach has proven useful for detecting disease
      susceptible SNPs, evidence has shown that many of these are, in fact, false
      positives. Consequently, there is some ambiguity about the most suitable
      threshold for claiming genome-wide significance. Many believe that using lower p
      values will allow us to investigate the joint epistatic interactions between SNPs
      and provide better insights into phenotype expression. In this paper, we propose
      a novel framework, based on nonlinear transformations of combinatorically large
      SNP data, using stacked autoencoders, to identify higher-order SNP interactions.
      We focus on the challenging problem of classifying preterm births. Latent
      representations from original SNP sequences are used to initialize a deep
      learning classifier before it is fine-tuned for classification tasks. The
      findings show that important information pertaining to epistasis can be extracted
      from 4666 raw SNPs generated using logistic regression (p-value=$5?star 10^{-8}$)
      and used to fit a deep learning model and obtain results (Sen=0.9289,
      Spec=0.9591, Gini=0.9651, Logloss=0.3080, AUC=0.9825, MSE=0.0942) using 500
      hidden nodes.

PMID- 30183646
TI  - Neural Adaptive Backstepping Control of a Robotic Manipulator With Prescribed
      Performance Constraint.
AB  - This paper presents an adaptive neural network (NN) control of a two-degree-of
      freedom manipulator driven by an electrohydraulic actuator. To restrict the
      system output in a prescribed performance constraint, a weighted performance
      function is designed to guarantee the dynamic and steady tracking errors of joint
      angle in a required accuracy. Then, a radial-basis-function NN is constructed to
      train the unknown model dynamics of a manipulator by traditional backstepping
      control (TBC) and obtain the preliminary estimated model, which can replace the
      preknown dynamics in the backstepping iteration. Furthermore, an adaptive
      estimation law is adopted to self-tune every trained-node weight, and the
      estimated model is online optimized to enhance the robustness of the NN
      controller. The effectiveness of the proposed control is verified by comparative
      simulation and experimental results with Proportional-integral-derivative and TBC
      methods.

PMID- 30183647
TI  - Multiview Multitask Gaze Estimation With Deep Convolutional Neural Networks.
AB  - Gaze estimation, which aims to predict gaze points with given eye images, is an
      important task in computer vision because of its applications in human visual
      attention understanding. Many existing methods are based on a single camera, and
      most of them only focus on either the gaze point estimation or gaze direction
      estimation. In this paper, we propose a novel multitask method for the gaze point
      estimation using multiview cameras. Specifically, we analyze the close
      relationship between the gaze point estimation and gaze direction estimation, and
      we use a partially shared convolutional neural networks architecture to
      simultaneously estimate the gaze direction and gaze point. Furthermore, we also
      introduce a new multiview gaze tracking data set that consists of multiview eye
      images of different subjects. As far as we know, it is the largest multiview gaze
      tracking data set. Comprehensive experiments on our multiview gaze tracking data
      set and existing data sets demonstrate that our multiview multitask gaze point
      estimation solution consistently outperforms existing methods.

PMID- 30183648
TI  - Modeling of Noisy Acceleration Signals from Quasi-periodic Movements for Drift
      free Position Estimation.
AB  - OBJECTIVE: We present a novel approach to drift-free position estimation from
      noisy acceleration signals which often arise from quasi-periodic small-amplitude
      body movements. In contrast to the existing methods, this data-driven strategy is
      designed to properly describe time-variant harmonic structures in single-channel
      acceleration signals for low signal-to-noise ratios. METHODS: It comprises three
      processing steps: (1) short-time modeling of acceleration dynamics (instantaneous
      harmonic amplitudes and phases) in the analysis frame, (2) analytical integration
      which yields short-time position, and (3) overlap-add recombination for full
      length position synthesis. RESULTS: The comparative results, obtained from the
      medio-lateral X-acceleration components from 30s Chair Stand Test recordings,
      suggest that the proposed method outperforms two state-of-the-art reference
      methods in terms of Euclidean error, root mean square error, correlation
      coefficient and harmonic-to-noise ratio. CONCLUSION: A major benefit of the
      method is that acceleration signal components unrelated to movement are
      suppressed in the whole analysis bandwidth, which allows for position estimation
      completely free of low-frequency artifacts. SIGNIFICANCE: We believe that the
      method can be useful in frailty assessment in elderly population, as well as in
      clinical applications related to gait analysis in aging and rehabilitation.

PMID- 30183649
TI  - Parkinson's Disease Diagnosis via Joint Learning from Multiple Modalities and
      Relations.
AB  - Parkinson's disease (PD) is a neurodegenerative progressive disease that mainly
      affects the motor systems of patients. To slow this disease deterioration, early
      and accurate diagnosis of PD is an effective way, which alleviates mental and
      physical sufferings by clinical intervention. In this paper, we propose a joint
      regression and classification framework for PD diagnosis via magnetic resonance
      and diffusion tensor imaging data. Specifically, we devise a unified multi-task
      feature selection model to explore multiple relationships among features,
      samples, and clinical scores. We regress four clinical variables of depression,
      sleep, olfaction, cognition scores, as well as perform the classification of PD
      disease from the multi-modal data. The multi-task model explores the
      relationships at the level of clinical scores, image features, and subjects, to
      select the most informative and diseased-related features for diagnosis. The
      proposed method is evaluated on the public Parkinson's progression markers
      initiative (PPMI) dataset. The extensive experimental results show that the multi
      task framework can effectively boost the performance of regression and
      classification and outperforms other state-of-the-art methods. The computerized
      predictions of clinical scores and label for PD diagnosis may offer quantitative
      reference for decision support as well.

PMID- 30183650
TI  - Boosting Cooperative Coevolution for Large Scale Optimization With a Fine-Grained
      Computation Resource Allocation Strategy.
AB  - Cooperative coevolution (CC) has shown great potential for solving large-scale
      optimization problems (LSOPs). However, traditional CC algorithms often waste
      part of the computation resource (CR) as they equally allocate CR among all
      subproblems. The recently developed contribution-based CC algorithms improve the
      traditional ones to a certain extent by adaptively allocating CR according to
      some heuristic rules. Different from existing works, this paper explicitly
      constructs a mathematical model for the CR allocation (CRA) problem in CC and
      proposes a novel fine-grained CRA (FCRA) strategy by fully considering both the
      theoretically optimal solution of the CRA model and the evolution characteristics
      of CC. FCRA takes a single iteration as a basic CRA unit and always selects the
      subproblem which is most likely to make the largest contribution to the total
      fitness improvement to undergo a new iteration, where the contribution of a
      subproblem at a new iteration is estimated according to its current contribution,
      current evolution status, as well as the estimation for its current contribution.
      We verified the efficiency of FCRA by combining it with the success-history-based
      adaptive differential evolution which is an excellent DE variant but has never
      been employed in the CC framework. Experimental results on two benchmark suites
      for LSOPs demonstrate that FCRA significantly outperforms existing CRA strategies
      and the resulting CC algorithm is highly competitive in solving LSOPs.

PMID- 30183651
TI  - A Deep Evaluator for Image Retargeting Quality by Geometrical and Contextual
      Interaction.
AB  - An image is compressed or stretched during the multidevice displaying, which will
      have a very big impact on perception quality. In order to solve this problem, a
      variety of image retargeting methods have been proposed for the retargeting
      process. However, how to evaluate the results of different image retargeting is a
      very critical issue. In various application systems, the subjective evaluation
      method cannot be applied on a large scale. So we put this problem in the accurate
      objective-quality evaluation. Currently, most of the image retargeting quality
      assessment algorithms use simple regression methods as the last step to obtain
      the evaluation result, which are not corresponding with the perception simulation
      in the human vision system (HVS). In this paper, a deep quality evaluator for
      image retargeting based on the segmented stacked AutoEnCoder (SAE) is proposed.
      Through the help of regularization, the designed deep learning framework can
      solve the overfitting problem. The main contributions in this framework are to
      simulate the perception of retargeted images in HVS. Especially, it trains two
      separated SAE models based on geometrical shape and content matching. Then, the
      weighting schemes can be used to combine the obtained scores from two models.
      Experimental results in three well-known databases show that our method can
      achieve better performance than traditional methods in evaluating different image
      retargeting results.

PMID- 30183652
TI  - Adaptive Fuzzy Quantized Control for Nonlinear Systems With Hysteretic Actuator
      Using a New Filter-Connected Quantizer.
AB  - This paper aims at the issue of adaptive fuzzy quantized control for a class of
      uncertain nonlinear systems preceded by unknown actuator hysteresis. One
      challenging problem that obstructs the development of the control scheme is that
      the direct application of the quantized signal containing high-frequency
      components to the hysteretic actuator will lead to system performance
      deterioration. To resolve this challenge, we propose a filter-connected quantizer
      in which a hysteretic quantizer is employed to reduce the communication rate and
      an adaptive high-cut filter is designed to smooth the hysteresis input.
      Furthermore, based on fuzzy logic systems' online approximation capability, a
      novel adaptive fuzzy control scheme involves a new control strategy and an
      adaptive strategy is constructed via a backstepping technique. It is proved that
      the proposed control scheme guarantees the tracking error is asymptotically
      convergent to an adjustable neighborhood of zero and all of the closed-loop
      signals are uniform ultimate bounded. Lastly, simulations are conducted to
      further verify our theoretical results.

PMID- 30183653
TI  - A Learning-Based Hierarchical Control Scheme for an Exoskeleton Robot in Human
      Robot Cooperative Manipulation.
AB  - Exoskeleton robots can assist humans to perform activities of daily living with
      little effort. In this paper, a hierarchical control scheme is presented which
      enables an exoskeleton robot to achieve cooperative manipulation with humans. The
      control scheme consists of two layers. In low-level control of the upper limb
      exoskeleton robot, an admittance control scheme with an asymmetric barrier
      Lyapunov function-based adaptive neural network controller is proposed to enable
      the robot to be back drivable. In order to achieve high-level interaction, a
      strategy for learning human skills from demonstration is proposed by utilizing
      Gaussian mixture models, which consists of the learning and reproduction phase.
      During the learning phase, the robot observes and learns how a demonstrator
      performs a specific impedance-based task successfully, and in the reproduction
      phase, the robot can provide the subjects with just enough assistance by
      extracting human skills from demonstrations to prevent the motion of the robot
      end-effector deviating far from desired ones, due to variation in the interaction
      force caused by environmental disturbances. Experimental results of two different
      tasks show that the proposed control scheme can provide human subjects with
      assistance as needed during cooperative manipulation.

PMID- 30183654
TI  - Event-Triggered Consensus of Homogeneous and Heterogeneous Multiagent Systems
      With Jointly Connected Switching Topologies.
AB  - This paper investigates the distributed event-based consensus problem of
      switching networks satisfying the jointly connected condition. Both the state
      consensus of homogeneous linear networks and the output consensus of
      heterogeneous networks are studied. Two kinds of event-based protocols based on
      local sampled information are designed, without the need to solve any matrix
      equation or inequality. Theoretical analysis indicates that the proposed event
      based protocols guarantee the achievement of consensus and the exclusion of Zeno
      behaviors for jointly connected undirected switching graphs. These protocols,
      relying on no global knowledge of the network topology and independent of
      switching rules, can be devised and utilized in a completely distributed manner.
      They are able to avoid continuous information exchanges for either controllers'
      updating or triggering functions' monitoring, which ensures the feasibility of
      the presented protocols.

PMID- 30183655
TI  - Autoimmune Aspects of Kawasaki Disease.
AB  - Kawasaki disease (KD) is classified as a medium-sized vasculitis of systemic
      vasculitis syndrome characterized by hypercytokinemia. Although the etiology of
      KD remains unidentified, epidemiological features point to the role of infection
      and genetic predisposition. Recent studies revealed endothelial damage and
      resultant thrombin generation, as well as B-cell activation during the acute
      phase of KD. Several anti-endothelial cell autoantibodies (AECAs) have been
      identified in KD patients. Taken together with the recently developed concept of
      immunothrombosis, a potential pathogenic mechanism for KD emerges. First, some
      polyclonal antibodies generated against invading microorganisms would exhibit
      cross-reactivity toward endothelial cell components and become dominant during
      affinity maturation. AECA binding to endothelial cells would cause endothelial
      activation or damage, with proinflammatory cytokine release, fostering a
      hypercoagulable state by leukocyte activation by proinflammatory cytokines. This,
      in turn, would lead to coronary artery lesions. KD vasculitis might be initiated
      upon AECA binding to the vasa vasorum and progress to panvasculitis and a
      vulnerable vessel wall, resulting in an aneurysm. The aneurysm would cause flow
      recirculation and alteration of wall shear stress. Consequently, platelets
      activated by shear stress, along with ultra-large von Willebrand factor (VWF)
      released by endothelial cells, would cause platelet-driven arterial thrombosis.
      Autoimmunity-associated thrombosis initiated by AECA binding to endothelial cells
      might play a major role in the pathogenesis of certain subtypes of KD. The notion
      of KD consisting of subtypes, the major one of which is AECA-associated
      vasculitis, will help facilitate a better understanding of KD and further promote
      early and accurate diagnosis, which remains challenging.

PMID- 30183656
TI  - False-positive results of serological tests for allergy in alcoholics.
AB  - BACKGROUND: Alcohol consumption is associated with enhanced Th2 immune responses.
      Aim: To investigate the frequency of false-positive serological tests of allergy
      in alcoholics. METHODS: A total of 138 alcoholic patients consecutively admitted
      to hospital underwent a panel of allergy tests that included serum total IgE, a
      multiallergen IgE test (UniCAP Phadiatop), and skin prick tests to relevant
      aeroallergens in the area, which were considered the standard reference for
      atopy. In selected cases with positive specific IgE (sIgE) to cross-reactive
      carbohydrate determinants (CCDs) on ImmunoCAP, we determined sIgE to Hymenoptera
      venom components (ADVIA Centaur) and a microarray of 103 allergen components
      (ISAC). RESULTS: Increased (>170 IU/mL) serum total IgE was observed in 59/110
      (54%) of non-atopic (skin prick test-negative) alcoholics. Forty-six non-atopic
      alcoholics (42%) had a positive multiallergen IgE test. This finding was closely
      associated with high serum concentrations of total IgE and sIgE to CCDs. The vast
      majority of alcoholics with positive CCD-sIgE showed positivity to glycosylated
      plant and Hymenoptera allergen components on ISAC and ADVIA Centaur. Only one out
      of 26 patients with positive sIgE to CCD and Hymenoptera venoms developed
      honeybee venom allergy after a median follow-up of 166 months. Measurements of
      sIgE to CCD markers on ImmunoCAP, ADVIA Centaur, and ISAC showed imperfect
      correlation. CONCLUSIONS: Serological tests for allergy should be interpreted
      with caution in alcoholics, who frequently show increased levels of total IgE,
      CCD-sIgE and subsequent positivity of sIgE to glycosylated allergen components,
      irrespective of the method used.

PMID- 30183657
TI  - Accurate of the diagnosis of allergy reactions at the Emergency Department.
AB  - BACKGROUND: Suspicion of an acute allergic reaction is a common reason for
      attending Emergency Departments (ED). However, little work has been performed
      comparing the initial diagnosis made in the ED of patients with suspected
      allergic reaction, with the definitive diagnosis made subsequently in the allergy
      department (AD). Objective: Compare details of the initial diagnoses given in the
      ED relating to allergy with the final diagnoses performed in the AD. METHODS:
      Patients attending the ED of two hospitals with suspected allergic reactions were
      prospectively enrolled based on keywords. A certified allergy specialist revised
      the ED records of these patients and, if suggestive of an allergic reaction, the
      patients were scheduled for further evaluation at the allergy clinic. RESULTS: In
      total, 2000 patients were enrolled between April 2013-October 2015, of which 1333
      passed the initial revision and underwent further evaluation. Of these, 528
      underwent allergological study and 206 were confirmed as allergic. Regarding drug
      allergy, non-steroidal anti-inflammatory drugs were the most common triggers,
      followed by beta-Lactams; in food allergy, plant-based foods were the most
      common. Only 16.4% of patients confirmed as having anaphylaxis in the AD were
      initially diagnosed as such in the ED. CONCLUSIONS: Of the 528 patients that
      finally underwent full allergological study, less than half could be confirmed as
      allergic. Moreover, there appears to be an underdiagnosis of anaphylaxis in ED.
      Better communication between ED and AD is necessary to improve this situation and
      improve the diagnosis and management of these patients.

PMID- 30183658
TI  - Is quantitative sIgE serology suitable to distinguish between silent
      sensitization and allergic rhinitis to D. pteronyssinus?
AB  - BACKGROUND AND OBJECTIVE: Recently, an increasing number of studies focus on the
      debate whether provocation tests might be replaceable by specific IgE serology in
      patients sensitized to airborne allergens. Objective: Our study aimed to analyse
      the concordance between a nasal provocation test with Dermatophagoides
      pteronyssinus and specific IgE measurements in real-life data. MATERIAL AND
      METHODS: In 223 patients with proven sensitization to Dermatophagoides
      pteronyssinus, the concordance between the result of the provocation test and the
      IgE titer against several house dust mite components and extracts was
      retrospectively analysed. RESULTS: In contrast to other studies, the anti-Der p 1
      level alone was not suitable at all to distinguish between silent sensitization
      and allergy to Dermatophagoides pteronyssinus. ROC curve analysis revealed that
      the sum of sIgE against Der p 1 and Der p 2 is - after adjustment to the total
      serum IgE - the best parameter to discriminate between clinically silent and
      relevant sensitization, however far from reaching a sufficient diagnostic
      validity. CONCLUSIONS: Despite the high correlation between sIgE levels and
      symptoms, no serologic parameter had a sufficiently high accuracy to distinguish
      between silent sensitization and clinically relevant allergy. Therefore, nasal
      provocation tests remain the gold-standard to investigate the clinical relevance
      in Dermatophagoides pteronyssinus sensitization.

PMID- 30183659
TI  - Elevated exhaled nitric oxide in adolescents relates to incident allergic
      symptoms: a prospective cohort study.
AB  - BACKGROUND: The fraction of exhaled nitric oxide (FeNO) is a marker of type-2
      inflammation in the airways and elevated FeNO may precede development of allergic
      disease. The aim of the present study was to investigate the association between
      elevated FeNO and the development of allergic symptoms. METHODS: A total of 959
      adolescents from a general population answered, together with their parents, a
      standardized questionnaire, performed lung function and FeNO measurements at a
      baseline visit. Four years later, 921 of these subjects (96%) completed a to a
      great extent same version of the baseline questionnaire. RESULTS: Adolescents
      with self-reported incident allergic symptoms to cat (n = 50) or dog (n = 33) had
      higher baseline FeNO (p < 0.001) than subjects without allergic symptoms to cat
      and dog at either time point (n = 776 and n = 838, respectively). Adolescents
      with incident allergic symptoms to pollen did not have elevated baseline FeNO.
      The adjusted odds ratio [aOR (95% confidence interval)] for incident allergic
      symptoms to cat was 4.2 (2.2, 8.0) times higher if FeNO was > 75th percentile
      (vs. < 75th percentile) at baseline. This was consistent after exclusion of
      subjects with reported asthma, wheeze or rhinitis at baseline [aOR (95% CI) 8.6
      (3.0, 24.1)]. CONCLUSIONS: Elevated FeNO in adolescents related to an increased
      risk of developing allergic symptoms to cat and dog, but not pollen allergens,
      within four years.

PMID- 30183660
TI  - Hymenoptera Venom Allergy: Management of children and adults in clinical
      practice.
AB  - Hymenoptera venom allergy is an epidemiologically underestimated condition
      representing an important cause of morbidity worldwide. Preventing future
      allergic reactions in patients who have developed a systemic reaction is based on
      the correct management of emergency followed by a correct diagnosis, prescription
      of adrenaline autoinjectors and, where indicated, specific venom immunotherapy
      (VIT). Some epidemiological studies highlight the poor knowledge of this disease
      and the frequent inadequacy of its management. Moreover, they emphasize the
      importance of such a life-saving treatment as specific immunotherapy. The
      availability of high quality Hymenoptera venom extracts for diagnostic and
      therapeutic use has dramatically improved the prognosis and the quality of life
      of allergic patients. The subcutaneous VIT represents the most effective form of
      immunotherapy with allergen presently available, with a carry-over effect lasting
      up to several years after its interruption. This report on the management of
      children and adults allergic to Hymenoptera venom was drawn up by a panel of
      Italian experts. The main objective of this consensus is to review the scientific
      evidences related to diagnosis, therapy and management of patients allergic to
      Hymenoptera venom and is aimed to improve the knowledge about this disease and
      promote good clinical practices. Practical suggestions for a correct diagnosis,
      prescription of emergency therapy and immunotherapy, as well as strategies for
      taking care of patients' management are included.

PMID- 30183661
TI  - Limited long-term impact of insect venom immunotherapy on the micro-RNA landscape
      in whole blood.
AB  - BACKGROUND AND OBJECTIVE: To perform a genome-wide characterization of changes of
      microRNA (miRNA) expression in the course of VIT (venom immunotherapy). METHODS:
      miRNA was isolated form in the whole-blood of 13 allergic patients and 14
      controls, who showed no allergic reaction upon stings by honeybees and wasps. We
      analyzed 2549 different miRNAs from whole blood of these patients prior to VIT
      and 12 months after the start of the VIT. Differential expression results
      obtained on microarray platform were confirmed by quantitative real -time PCR
      (qRT-PCR). Out of the 13 patients, eight were confirmed to show a negative
      allergic reaction upon VIT thus indicating a successful VIT. RESULTS: By
      comparing time points prior and 12 month after ultra-rush venom immunotherapy
      (VIT), correlation and principal component analysis both indicate a limited
      effect of the VIT on the overall miRNA expression pattern. Volcano blot analysis
      based on raw p-values revealed few deregulated miRNAs with the majority of them
      being increasingly expressed after VIT as compared to prior VIT. Using the 50
      most altered miRNAs, there was no clear clustering according to the time points
      i.e. the time prior and the time after VIT. CONCLUSIONS: Our results indicate an
      overall low effect of VIT on the miRNA expression pattern in whole blood.

PMID- 30183662
TI  - Re: Degree of the Hazards of Silver-Containing Dressings on MRSA-Infected Wounds
      in Sprague-Dawley and Streptozotocin-Induced Diabetic Rat.

PMID- 30183663
TI  - Study on Comparison of DNA Damage and Apoptosis is too Flawed to be Clinically
      Relevant.

PMID- 30183664
TI  - Moving from the second to the third generation Roche PTH assays: what are the
      consequences for clinical practice?

PMID- 30183665
TI  - Host-response biomarkers for the diagnosis of bacterial respiratory tract
      infections.

PMID- 30183666
TI  - Evaluation of anthropometric parameters of central obesity in Pakistani children
      aged 5-12 years, using receiver operating characteristic (ROC) analysis.

PMID- 30183667
TI  - Does heart rate variability improve prediction of failed extubation in preterm
      infants?

PMID- 30183668
TI  - Antimicrobial activity and active compounds of a Rhus verniciflua Stokes extract.
AB  - The Rhus verniciflua Stokes (RVS) extract is used as a traditional herbal
      medicine in Southeast Asian countries such as Korea and China. In the present
      study, one phenolic acid and six flavonoids were isolated from an 80% ethanol RVS
      extract to examine their antimicrobial activities. These compounds were
      identified as 3',4',7-trihydroxyflavone (1), methyl gallate (2), gallic acid (3),
      fusti (4), fisetin (5), butin (6), and sulfuretin (7) by matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry and nuclear magnetic
      resonance spectroscopy. The antimicrobial activities of compounds 5 and 6 (at a
      dose of 16 MUg/mL each) were superior to that of the control, cycloheximide (at a
      dose of 25 MUg/mL), against Hypocrea nigricans; additionally, the activities of
      compounds 1 and 2 (at a dose of 8 MUg/mL each) were superior to the control
      against Penicillium oxalicum. Also, chemical compounds 1 and 5 (at a dose of 16
      MUg/mL each) had higher activities than the control (25 MUg/mL) against
      Trichoderma virens. Chemical compound 1 (at a dose of 8 MUg/mL) had a similar
      activity to that of the control against Bacillus subtilis. The obtained results
      suggest that the RVS extract could be a promising food and nutraceutical source
      because of the antimicrobial properties of its phenolic compounds.

PMID- 30183669
TI  - Structure of parasite communities in urban environments: the case of helminths in
      synanthropic rodents.
AB  - Identifying patterns with sufficient predictive power is a constant challenge for
      ecologists to address ecological problems related to species conservation,
      pollution or infectious disease control. During the last years, the amounts of
      parasitological studies in this sense increased, but they are still scarce in
      urban environments. The main aim of this study was to investigate if the helminth
      communities of urban rodents are structured within host assembly (compound
      community) or they are a result of random events occurring at each individual
      host scale (infracommunity). A total of 203 rodents belonging to four species,
      Rattus rattus (Linnaeus), Rattus norvegicus (Berkenhout), Mus musculus Linnaeus
      and the native Oligoryzomys flavescens (Waterhouse) and captured in different
      landscape units of the City of Buenos Aires (industrial-residential
      neighbourhoods, shantytowns and parklands) were analysed. The results showed that
      infracommunities could be grouped according to composition and relative
      abundances and that they respond to the structure of the host community. Thus,
      the component communities defined in this study could be identified as subsets of
      the compound community (rodent assemblage) and infracommunities (each host) as
      random samples within each one. Quantitative differences among component
      communities were denoted by comparing the infection levels of helminths described
      as central species. Therefore, infracommunities of R. norvegicus and O.
      flavescens were the most predictable because of the high abundance of the
      nematodes Heterakis spumosa Schneider, 1866 and Nippostrongylus brasiliensis
      (Travassos, 1914), and Stilestrongylus flavescens (Sutton et Durette-Desset,
      1991), respectively. Several mechanisms contribute to complexity of the structure
      of parasite communities, where specific parasites, definitive and intermediate
      hosts, and environmental and anthropogenic factors all play a role in the
      dynamics of the compound community.

PMID- 30183670
TI  - Isolated highly localized bands in YBi2 monolayer caused by 4f orbitals.
AB  - The novel electronic structures can induce unique physical properties in two
      dimensional (2D) materials. In this work, we report isolated highly localized
      bands (HLB) in [Formula: see text] monolayer by the first-principle calculations
      within generalized gradient approximation (GGA) plus spin-orbit coupling (SOC).
      It is found that [Formula: see text] monolayer is an indirect-gap semiconductor
      using both GGA and GGA+SOC. The calculations reveal that Yb-4f orbitals
      constitute isolated HLB below the Fermi level at the absence of SOC, and the
      bands are split into the j  =  7/2 and j  =  5/2 states with SOC. The isolated
      HLB can lead to a very large Seebeck coefficient and very low electrical
      conductivity in p-type doping by producing very large effective mass of the
      carrier. It is proved that isolated HLB have very strong stability against
      strain, which is very important for practical application. When the onsite
      Coulomb interaction is added to the Yb-4f orbitals, isolated HLB persist, and
      only their relative positions in the gap change. These findings open a new window
      to search for novel electronic structures in 2D materials.

PMID- 30183671
TI  - Comment on 'New photoplethysmogram indicators for improving cuffless and
      continuous blood pressure estimation accuracy'.
AB  - OBJECTIVE: A recent study investigated the potential utility of new
      photoplethysmogram (PPG) indicators to improve cuffless continuous blood pressure
      (BP) measurement. APPROACH: In this Comment we provide additional discussion of
      the physiology underlying PPG- and pulse arrival time (PAT)-based BP measurement.
      We also discuss validation of these measurements. MAIN RESULTS: Changes in PPG
      features and PAT can occur independently of BP. Any study validating BP
      measurement based on PPG features or PAT should include a variety of calibration
      independent physiological challenges affecting BP. SIGNIFICANCE: PPG/PAT-based BP
      measurement has been investigated extensively as an alternative to cuff-based BP
      measurement. We feel the inherent physiological confounding in PPG/PAT-based
      measurement makes it unlikely that it will be of clinical value.

PMID- 30183672
TI  - From Klein to anti-Klein tunneling in graphene tuning the Rashba spin-orbit
      interaction or the bilayer coupling.
AB  - We calculate the transmission coefficient for a particle crossing a potential
      barrier in monolayer graphene with Rashba spin-orbit coupling and in bilayer
      graphene. We show that in both cases one can go from Klein tunneling regime,
      characterized by perfect normal transmission, to anti-Klein tunneling regime,
      with perfect normal reflection, by tuning the Rashba spin-orbit coupling for a
      monolayer or the interplane coupling for a bilayer graphene. We show that the
      intermediate regime is characterized by a non-monotonic behavior with
      oscillations and resonances in the normal transmission amplitude as a function of
      the coupling and of the potential parameters.

PMID- 30183673
TI  - Dynamic signal quality index for electrocardiograms.
AB  - OBJECTIVE: The advent of telehealth applications and remote patient monitoring
      has led to an increasing need for continuous signal quality monitoring to ensure
      high diagnostic accuracy of the recordings. Cardiovascular diseases often
      manifest electrophysiological anomalies, therefore the electrocardiogram (ECG) is
      one of the most used signals for diagnostic applications. Various types of noise
      and artifacts are not uncommon in ECG recordings and assessing the quality of the
      signal is essential prior to any clinical interpretation. In this study, a
      dynamic signal quality index (dSQI) is introduced using a new time-frequency
      template-based approach. APPROACH: A smoothed pseudo Wigner-Ville transform is
      applied to derive the time-frequency patterns of the ECG signal. A weighted cross
      correlation function then assigns a score between 0 to 1 to each identified ECG
      beat to indicate the signal quality. It evaluates the consistency of the patterns
      over an ECG window of multiple beats. To assess the performance of the dSQI, the
      algorithm was tested with the public databases on PhysioNet, alongside other
      state-of-the-art indexes for comparison. The recordings were classified into
      noisy and normal recordings, as well as noisy data versus the recordings from
      patients with heart diseases and abnormal rhythms. MAIN RESULTS: The results
      showed that dSQI outperformed previous metrics when used individually with an
      area under curve (AUC) of 93.18% for normal versus noisy and 93.69% for abnormal
      versus noisy. A support vector machine was also trained with different
      combinations of dSQI and other signal quality indexes, where dSQI showed to be
      among the best performing sets in classifying both normal versus noisy (97.4% on
      training set and 96.9% on test set) and abnormal versus noisy (97.6% on training
      set and 96.3% on test set). The method was also tested on the MIT-BIH Arrhythmia
      Database to evaluate dSQI in common arrhythmia cases. SIGNIFICANCE: The results
      indicate that dSQI provides a more accurate and continuous scalar metric for beat
      by-beat ECG quality assessment, even for those with arrhythmia.

PMID- 30183675
TI  - Adaptive template matching of photoplethysmogram pulses to detect motion
      artefact.
AB  - OBJECTIVE: The photoplethysmography (PPG) signal, commonly used in the healthcare
      settings, is easily affected by movement artefact leading to errors in the
      extracted heart rate and SpO2 estimates. This study aims to develop an online
      artefact detection system based on adaptive (dynamic) template matching, suitable
      for continuous PPG monitoring during daily living activities or in the intensive
      care units (ICUs). APPROACH: Several master templates are initially generated by
      applying principal component analysis to data obtained from the PhysioNet MIMIC
      II database. The master template is then updated with each incoming clean PPG
      pulse. The correlation coefficient is used to classify the PPG pulse into either
      good or bad quality categories. The performance of our algorithm was evaluated
      using data obtained from two different sources: (i) our own data collected from
      19 healthy subjects using the wearable Sotera Visi Mobile system (Sotera Wireless
      Inc.) as they performed various movement types; and (ii) ICU data provided by the
      PhysioNet MIMIC II database. The developed algorithm was evaluated against a
      manually annotated 'gold standard' (GS). MAIN RESULTS: Our algorithm achieved an
      overall accuracy of 91.5%  +/-  2.9%, with a sensitivity of 94.1%  +/-  2.7% and
      a specificity of 89.7%  +/-  5.1%, when tested on our own data. When applying the
      algorithm to data from the PhysioNet MIMIC II database, it achieved an accuracy
      of 98.0%, with a sensitivity and specificity of 99.0% and 96.1%, respectively.
      SIGNIFICANCE: The proposed method is simple and robust against individual
      variations in the PPG characteristics, thus making it suitable for a diverse
      range of datasets. Integration of the proposed artefact detection technique into
      remote monitoring devices could enhance reliability of the PPG-derived
      physiological parameters.

PMID- 30183674
TI  - Impact of potentially variable RBE in liver proton therapy.
AB  - Currently, the relative biological effectiveness (RBE) is assumed to be constant
      with a value of 1.1 in proton therapy. Although trends of RBE variations are well
      known, absolute values in patients are associated with considerable
      uncertainties. This study aims to evaluate the impact of a variable proton RBE in
      proton therapy liver trials using different fractionation schemes. Sixteen liver
      cancer cases were evaluated assuming two clinical schedules of 40 Gy/5 fractions
      and 58.05 Gy/15 fractions. The linear energy transfer (LET) and physical dose
      distribution in patients were simulated using Monte Carlo. The variable RBE
      distribution was calculated using a phenomenological model, considering the
      influence of the LET, fraction size and alpha/beta value. Further, models to
      predict normal tissue complication probability (NTCP) and tumor control
      probability (TCP) were used to investigate potential RBE effects on outcome
      predictions. Applying the variable RBE model to the 5 and 15 fractions schedules
      results in an increase in mean fraction-size equivalent dose (FED) to the normal
      liver of 5.0% and 9.6% respectively. For patients with a mean FED to the normal
      liver larger than 29.8 Gy, this results in a non-negligible increase in the
      predicted NTCP of the normal liver averaging 11.6%, ranging from 2.7% to 25.6%.
      On the other hand, decrease in TCP was less than 5% for both fractionation
      regimens for all patients when assuming a variable RBE instead of constant.
      Consequently, the difference in TCP between the two fractionation schedules did
      not change significantly assuming a variable RBE while the impact on the NTCP
      difference was highly case specific. In addition, both the NTCP and TCP decrease
      with increasing alpha/beta value for both fractionation schemes, with the
      decreases being more pronounced when using a variable RBE compared to using RBE 
      =  1.1. Assuming a constant RBE of 1.1 most likely overestimates the therapeutic
      ratio in proton therapy for liver cancer, predominantly due to underestimation of
      the RBE-weighted dose to the normal liver. The impact of applying a variable RBE
      (as compared to RBE  =  1.1) on the NTCP difference of the two fractionation
      regimens is case dependent. A variable RBE results in a slight increase in TCP
      difference. Variations in patient radiosensitivity increase when using a variable
      RBE.

PMID- 30183676
TI  - Changes in f-wave characteristics during cryoballoon catheter ablation.
AB  - OBJECTIVE: Changes in ECG-derived parameters are studied in atrial fibrillation
      (AF) patients undergoing cryoballoon catheter ablation. APPROACH: Parameters
      characterizing f-wave frequency, morphology by phase dispersion, and amplitude
      are estimated using a model-based statistical approach. These parameters are
      studied before, during, and after ablation, as well as for AF type
      (paroxysmal/persistent). Seventy-seven (49/28 paroxysmal/persistent) AF patients
      undergoing de novo catheter ablation are included in the study, out of which 31
      (16/15 paroxysmal/persistent) were in AF during the whole procedure. A signal
      quality index (SQI) is used to identify analyzable segments. MAIN RESULTS: f-wave
      frequency decreased significantly during ablation (p  =  0.001), in particular
      after ablation of the inferior right pulmonary vein (p  <  0.05). Frequency and
      phase dispersion differed significantly between paroxysmal and persistent AF (p 
      =  0.001 and p  <  0.05, respectively). SIGNIFICANCE: This study demonstrates
      that a decrease in f-wave frequency can be distinguished during catheter
      ablation. The use of an SQI ensures reliable analysis and produces results
      significantly different from those obtained without an SQI.

PMID- 30183677
TI  - An augmented correlation framework for the estimation of tumour translational and
      rotational motion during external beam radiotherapy treatments using intermittent
      monoscopic x-ray imaging and an external respiratory signal.
AB  - Increasing evidence shows that intrafraction tumour motion monitoring must
      include both six degrees of freedom (6DoF): 3D translations and 3D rotations.
      Existing real-time algorithms for 6DoF target motion estimation require
      continuous intrafraction fluoroscopic imaging at high frequency, thereby exposing
      patients to additional high imaging dose. This paper presents the first method
      capable of 6DoF motion monitoring using intermittent 2D kV imaging and a
      continuous external respiratory signal. Our approach is to optimise a state
      augmented linear correlation model between an external signal and internal 6DoF
      motion. In standard treatments, the model can be built using information obtained
      during pre-treatment cone beam CT (CBCT). Real-time 6DoF tumor motion can then be
      estimated using just the external signal. Intermittent intrafraction kV images
      are used to update the model parameters, accounting for changes in correlation
      and baseline shifts. The method was evaluated in silico using data from 6 lung
      SABR patients, with the internal tumour motion recorded with electromagnetic
      beacons and the external signal from a bellows belt. Projection images from CBCT
      (10 Hz) and intermittent kV images were simulated by projecting the 3D Calypso
      beacon positions onto an imager. IMRT and VMAT treatments were simulated with
      increasing imaging update intervals: 0.1 s, 1 s, 3 s, 10 s and 30 s. For all the
      tested clinical scenarios, translational motion estimates with our method had sub
      mm accuracy (mean) and precision (standard deviation) while rotational motion
      estimates were accurate to  <[Formula: see text] and precise to [Formula: see
      text]. Motion estimation errors increased as the imaging update interval
      increased. With the largest imaging update interval (30 s), the errors were
      [Formula: see text] mm, [Formula: see text] mm and [Formula: see text] mm for
      translation in the left-right, superior-inferior and anterior-posterior
      directions, respectively, and [Formula: see text], [Formula: see text] and
      [Formula: see text] for rotation around the aforementioned axes for both VMAT and
      IMRT treatments. In conclusion, we developed and evaluated a novel method for
      highly accurate real-time 6DoF motion monitoring on a standard linear accelerator
      without requiring continuous kV imaging. The proposed method achieved sub-mm and
      sub-degree accuracy on a lung cancer patient dataset.

PMID- 30183678
TI  - Characterization and reduction of exercise-based motion influence on heart rate
      variability using accelerator signals and channel decoding in the time-frequency
      domain.
AB  - OBJECTIVE: Heart rate variability (HRV) is defined as the variation of the
      heart's beat to beat time intervals. Although HRV has been studied for decades,
      its response to stress tests and off-rest measurements is still under
      investigation. In this paper, we studied the influence of motion on HRV
      throughout different exercise tests, including a maximal running of healthy
      recreational runners, cycling, and walking tests of healthy subjects. APPROACH:
      In our proposed method, we utilized the motion trajectory (which is known to
      exist partially in HRV) measured by a three-channel accelerator (ACC). We then
      estimated their shares in HRV using a wearable electrocardiogram (ECG) and an
      error-correcting problem formulation. In this method, we characterized the motion
      components of three orthogonal directions induced into the HRV signal, and then
      we suppressed the estimated motion artefact to construct a motion-attenuated
      spectrogram. Main results and Significance: Our analysis showed that HRV in the
      exercise context is susceptible to motion artefacts. Furthermore, the
      interpretation of autonomic nervous system (ANS) activity and HRV indices
      throughout exercise has a high margin of error depending on the intensity level,
      type of exercise, and motion trajectory. Our experiment on 84 healthy subjects
      throughout mid-intensity cycling and walking tests showed 39% and 32% influence
      on average, respectively. In addition, our proposed method revealed through a
      maximal running test with 11 runners that motion can describe on average 20%-40%
      of the HRV high-frequency (HF) energy at different workloads of running.

PMID- 30183679
TI  - The impact of secondary fragments on the image quality of helium ion imaging.
AB  - Single-event ion imaging enables the direct reconstruction of the relative
      stopping power (RSP) information required for ion-beam therapy. Helium ions were
      recently hypothesized to be the optimal species for such technique. The purpose
      of this work is to investigate the effect of secondary fragments on the image
      quality of helium CT (HeCT) and to assess the performance of a prototype proton
      CT (pCT) scanner when operated with helium beams in Monte Carlo simulations and
      experiment. Experiments were conducted installing the U.S. pCT consortium
      prototype scanner at the Heidelberg Ion-Beam Therapy Center (HIT). Simulations
      were performed with the scanner using the TOPAS toolkit. HeCT images were
      reconstructed for a cylindrical water phantom, the CTP404 (sensitometry), and the
      CTP528 (line-pair) [Formula: see text] (r) modules. To identify and remove
      individual events caused by fragmentation, the multistage energy detector of the
      scanner was adapted to function as a [Formula: see text] telescope. The use of
      the developed filter eliminated the otherwise arising ring artifacts in the HeCT
      reconstructed images. For the HeCT reconstructed images of a water phantom, the
      maximum RSP error was improved by almost a factor 8 with respect to unfiltered
      images in the simulation and a factor 10 in the experiment. Similarly, for the
      CTP404 module, the mean RSP accuracy improved by a factor 6 in both the
      simulation and the experiment when the filter was applied (mean relative error
      0.40% in simulation, 0.45% in experiment). In the evaluation of the spatial
      resolution through the CTP528 module, the main effect of the filter was noise
      reduction. For both simulated and experimental images the spatial resolution was 
      ~4 lp cm-1. In conclusion, the novel filter developed for secondary fragments
      proved to be effective in improving the visual quality and RSP accuracy of the
      reconstructed images. With the filter, the pCT scanner is capable of accurate
      HeCT imaging.

PMID- 30183680
TI  - Detection of acute periodontal pain from physiological signals.
AB  - OBJECTIVE: To investigate the feasibility of the detection of brief orofacial
      pain sensations from easily recordable physiological signals by means of machine
      learning techniques. APPROACH: A total of 47 subjects underwent periodontal
      probing and indicated each instance of pain perception by means of a push button.
      Simultaneously, physiological signals were recorded and, subsequently, autonomic
      indices were computed. By using the autonomic indices as input features of a
      classifier, a pain indicator based on fusion of the various autonomic mechanisms
      was achieved. Seven patients were randomly chosen for the test set. The rest of
      the data were utilized for the validation of several classifiers and feature
      combinations by applying leave-one-out-cross-validation. MAIN RESULTS: During the
      validation process the random forest classifier, using frequency spectral bins of
      the ECG, wavelet level energies of the ECG and PPG, PPG amplitude, and SPI as
      features, turned out to be the best pain detection algorithm. The final test of
      this algorithm on the independent test dataset yielded a sensitivity and
      specificity of 71% and 70%, respectively. SIGNIFICANCE: Based on these results,
      fusion of autonomic indices by applying machine learning techniques is a
      promising option for the detection of very brief instances of pain perception,
      that are not covered by the established indicators.

PMID- 30183681
TI  - The impact of dual- and multi-energy CT on proton pencil beam range
      uncertainties: a Monte Carlo study.
AB  - The purpose of this work is to evaluate the impact of single-, dual- and multi
      energy CT (SECT, DECT and MECT) on proton range uncertainties in a patient like
      geometry and a full Monte Carlo environment. A virtual patient is generated from
      a real patient pelvis CT scan, where known mass densities and elemental
      compositions are overwritten in each voxel. Simulated CT images for SECT, DECT
      and MECT are generated for two limiting cases: (1) theoretical and idealistic CT
      numbers only affected by Gaussian noise (case A, the best scenario) and (2)
      reconstructed polyenergetic sinograms containing beam hardening, projection-based
      Poisson noise, and reconstruction artifacts (case B, the worst scenario).
      Conversion of the simulated SECT images into Monte Carlo inputs is done following
      the stoichiometric calibration method. For DECT and MECT, the Bayesian
      eigentissue decomposition method of Lalonde (2017 Med. Phys. 44 5293-302) is
      used. Pencil beams from seven different angles around the virtual patient are
      simulated using TOPAS to assess the performance of each method. Percentage depth
      doses curves (PDD) are compared to ground truth in order to determine the
      accuracy of range prediction of each imaging modality. For the idealistic images
      of case A, MECT and DECT slightly outperforms SECT. Root mean square (RMS) errors
      or 0.78 mm, 0.49 mm and 0.42 mm on R 80 mm, are observed for SECT, DECT and MECT
      respectively. In case B, PDD calculated in the MECT derived Monte Carlo inputs
      generally shows the best agreement with ground truth in both shape and position,
      with RMS errors of 2.03 mm, 1.38 mm and 0.86 mm for SECT, DECT and MECT
      respectively. Overall, the Bayesian eigentissue decomposition used with DECT
      systematically predicts proton ranges more accurately than the gold standard SECT
      based approach. When CT numbers are severely affected by imaging artifacts, MECT
      with four energy bins becomes more reliable than both DECT and SECT.

PMID- 30183682
TI  - Reply to Comment on 'New photoplethysmogram indicators for improving cuffless and
      continuous blood pressure estimation accuracy'.
AB  - OBJECTIVE: This article was written by the invitation of the editorial board of
      Physiological Measurement. It is a Reply to the Comment regarding our recently
      published paper entitled 'New photoplethysmogram indicators for improving
      cuffless and continuous blood pressure estimation accuracy' (Lin et al 2018
      Physiol. Meas. 29 025005). APPROACH: We appreciate van Helmond and Joseph's (2018
      Physiol. Meas. 098001) interests and comments on our previous paper. In the
      Comment, they discussed in detail the physiology underlying the pulse arrive time
      (PAT)-based methods for blood pressure (BP) measurement, and concluded that there
      are inherent physiological reasons precluding the development of an accurate
      continuous cuffless BP measurement using PAT-based methods. We could agree with
      the comments of van Helmond and Joseph about the physiology underlying PAT-based
      methods for BP measurement. It may be difficult to minimize the confounding
      effects of physiological factors such as pre-ejection period and smooth muscle
      tone, etc. However, in this Reply, we discuss some potential solutions to deal
      with these problems from an engineering point of view. MAIN RESULTS: When heart
      rate, more photoplethysmogram (PPG) features, PAT, robust machine learning
      models, and other techniques were adopted for BP estimation, it is promising for
      improving the accuracy of BP estimation to an acceptable range that can meet
      professional standards (e.g. Advancement of Medical Instrumentation (AAMI)
      standard, British Hypertension Society (BHS) protocol). SIGNIFICANCE: PAT- and/or
      PPG-based methods may be a promising technique for continuous and unobtrusive
      blood pressure measurement.

PMID- 30183683
TI  - Fano cavity test for electron Monte Carlo transport algorithms in magnetic
      fields: comparison between EGSnrc, PENELOPE, MCNP6 and Geant4.
AB  - A Fano cavity test was performed for four general-purpose Monte Carlo codes,
      EGSnrc, PENELOPE, MCNP6 and Geant4 to evaluate the accuracy of their electron
      transport algorithms in magnetic fields. In the simulations, a plane-parallel
      ionization chamber was modelled as a circular gas disk sandwiched between two
      circular solid wall disks. It was assumed that an isotropic and uniform line
      source per unit mass along the central axis of the gas and solid emits mono
      energetic electrons with energies 0.01, 0.1, 1.0 and 3.0 MeV at different
      magnetic field strengths 0, 0.35, 1.0, 1.5 and 3.0 T in the electron transport
      mode (no Bremsstrahlung). The relative difference between the calculated dose to
      the gas region and the initial total energy of emitted electrons per unit mass
      was defined as the accuracy of Monte Carlo codes. In all results, EGSnrc with the
      enhanced electric and magnetic field (EEMF) macros was not considerably sensitive
      to the step size parameters and showed accuracy less than 0.18%  +/-  0.06% with
      a coverage factor k  =  2. The other codes could not achieve competent accuracy
      with their default settings of step size parameters, compared to EGSnrc with the
      EEMF macros. With the step size parameters carefully selected, the accuracy of
      PENELOPE and MCNP6 was within 1.0% and 0.4%, respectively. However, Geant4 showed
      accuracy within 1.7% except in 3.0 T. EGSnrc with the EEMF macros achieved the
      best accuracy for the Fano test at the electron energies and the magnetic field
      strengths investigated in this study and thus, would be recommended to simulate
      dose responses of ionization chambers in the presence of magnetic fields.

PMID- 30183684
TI  - A method for optimizing planning target volume margins for patients receiving
      lung stereotactic body radiotherapy.
AB  - Lung stereotactic-body radiotherapy (SBRT) places additional requirements on
      targeting accuracy over standard approaches. In treatment planning, a tumour
      volume is geometrically expanded and the resulting planning target volume (PTV)
      is covered with the prescribed dose. This ensures full dose delivery despite
      various uncertainties encountered during treatment. We developed a retrospective
      technique for optimizing the PTV expansion for a patient population. The method
      relies on deformable image registration (DIR) of the planning CT to a treatment
      cone-beam CT (CBCT). The resulting transformation is used to map the planned
      target onto the treatment geometry, allowing the computation of the achieved
      target/PTV overlap. Basic validation of the method was performed using an
      anthropomorphic respiratory motion phantom. A self-validation technique was also
      implemented to allow estimation of the DIR error for the data being analyzed. Our
      workflow was used to retrospectively optimize PTV margin for 25 patients treated
      over 93 fractions. Targets for these patients were contoured on 4D CT images.
      SBRT delivery followed CBCT acquisition and a couch correction. A post-treatment
      CBCT was also acquired in some cases. Our basic validation demonstrated that the
      DIR-based technique is capable of transforming target volumes from planning CTs
      to treatment CBCTs with sub-mm accuracy. Our clinical analysis showed that the
      minimum percentages of target volumes covered for 3, 4, and 5 mm PTV margins were
      92.1, 97.6, and 99.2, respectively. Analyzing data acquired before and just after
      treatment demonstrated that margins exceeding 5 mm did not significantly improve
      coverage. Finally, a 5 mm PTV margin achieved  ?95% target volume coverage with 
      ?95% probability. Our technique is accurate, automated, self-validating, and
      incorporates complex ITV shapes/deformations to allow PTV margin optimization.
      The analysis of clinical data indicates a 5 mm PTV margin is optimal for our
      process. This approach is generalizable to other disease sites and treatment
      strategies.

PMID- 30183685
TI  - Classification of short single-lead electrocardiograms (ECGs) for atrial
      fibrillation detection using piecewise linear spline and XGBoost.
AB  - OBJECTIVE: Detection of atrial fibrillation is important for risk stratification
      of stroke. We developed a novel methodology to classify electrocardiograms (ECGs)
      to normal, atrial fibrillation and other cardiac dysrhythmias as defined by the
      PhysioNet Challenge 2017. APPROACH: More specifically, we used piecewise linear
      splines for the feature selection and a gradient boosting algorithm for the
      classifier. In the algorithm, the ECG waveform is fitted by a piecewise linear
      spline, and morphological features relating to the piecewise linear spline
      coefficients are extracted. XGBoost is used to classify the morphological
      coefficients and heart rate variability features. MAIN RESULTS: The performance
      of the algorithm was evaluated by the PhysioNet Challenge database (3658 ECGs
      classified by experts). Our algorithm achieved an average F 1 score of 81% for a
      10-fold cross-validation and also achieved 81% for F 1 score on the independent
      testing set. This score is similar to the top 9th score (81%) in the official
      phase of the PhysioNet Challenge 2017. SIGNIFICANCE: Our algorithm presents a
      good performance on multi-label short ECG classification with selected
      morphological features.

PMID- 30183686
TI  - Fabrication of an anthropomorphic heterogeneous mouse phantom for multimodality
      medical imaging.
AB  - This work presents a comprehensive methodology for constructing a tissue
      equivalent mouse phantom using image modeling and 3D printing technology. The
      phantom can be used in multimodality imaging and irradiation experiments, quality
      control, and management. Computed tomography (CT) images of a mouse were acquired
      and imported into 3D modeling software. A skeleton and skin shell models were
      segmented in the modeling software and manufactured using 3D printing technology.
      The bone model was constructed with VERO-WHITE printing material with additional
      ingredients, including a photosensitive resin, polyurethane epoxy resin, and
      acrylate. Acrylonitrile butadiene styrene resin material was used to construct
      the skin shell. The skin shell was attached to the skeleton and filled with a
      specially formulated gel to act as a soft tissue substitute. The gel consisted of
      agarose, micro-pearl powder, sodium chloride, and magnevist solution
      (gadopentetate dimeglumine). A micro-container filled with 18F-fluorodeoxyglucose
      (18F-FDG) radioactive tracer was placed in the abdomen for micro and human
      positron emission tomography (PET)/CT imaging. The mouse phantom had tissue
      equivalency in dose attenuation with x-rays and relaxation times with magnetic
      resonance imaging (MRI). The CT Hounsfield Unit (HU) range for the gel soft
      tissue material was 31-36 HU. The 3D printed bone mimetic material had equivalent
      tissue/bone contrast compared with in vivo mouse measurements with a mean value
      of 130  +/-  10 HU. At different magnetic field strengths, the T 1 relaxation
      time of the soft tissue was 382.75-506.48 ms, and T 2 was 51.11-70.76 ms. 18F-FDG
      tracer could be clearly observed in PET imaging. The 3D printed mouse phantom was
      successfully constructed with tissue-equivalent materials. Our model can be used
      for CT, MRI, and PET as a standard device for small-animal imaging and quality
      control.

PMID- 30183687
TI  - Relating ionization quenching in organic plastic scintillators to basic material
      properties by modelling excitation density transport and amorphous track
      structure during proton irradiation.
AB  - Ionization quenching in organic scintillators is usually corrected with methods
      that require careful assessment of the response relative to that of an ionization
      chamber. Here, we present a framework to compute ionization quenching correction
      factors (QCFs) from first principles for organic plastic scintillators exposed to
      ions. The tool solves the kinetic Blanc equation, of which the Birks model is a
      simplified solution, based on amorphous track structures models. As a
      consequence, ionization quenching correction factors can be calculated relying
      only on standard, tabulated scintillator material properties such as the density,
      light yield, and decay time. The tool is validated against experimentally
      obtained QCFs for two different organic plastic scintillators irradiated with
      protons with linear energy transfers (LETs) between 5-[Formula: see text]. The
      QCFs computed from amorphous track structure models and the BC-400 scintillator
      properties deviate less than 3% from the Birks model for LETs below [Formula: see
      text] and less than 5% for higher LETs. The agreement between experiments and the
      software for the BCF-12 scintillator is within 2% for LETs below [Formula: see
      text] and within 10% for LETs above, comparable to the experimental
      uncertainties. The framework is compiled into the open source software [Formula:
      see text] available for download. [Formula: see text] enables computations of
      QCFs in organic plastic scintillators exposed to ions independently of
      experimentally based quenching parameters in contrast to the Birks model.
      [Formula: see text] can improve the accuracy of correction factors and
      understanding of ionization quenching in scintillator dosimetry.

PMID- 30183688
TI  - Evaluating TOPAS for the calculation of backscatter factors for low energy x-ray
      beams.
AB  - For low x-ray energies, backscatter is an important parameter for determining the
      absorbed dose, making accurate knowledge of backscatter factors (BSFs) essential.
      BSFs can be difficult to measure experimentally so published values are often
      derived using Monte Carlo methods. This study evaluated the Monte Carlo code
      TOPAS as a tool for dose calculations for kilovoltage x-rays, and for calculating
      BSFs for energies ranging from 50 to 280 kVp. BSFs were also measured
      experimentally for comparison using Gafchromic EBT3 film and optically stimulated
      luminescence dosimeters (OSLs). The BSFs calculated using TOPAS were found to be
      consistent within 2% of the values published in the AAPM TG-61 protocol. The
      TOPAS BSF calculations were also found to be consistent with film measurements,
      typically within 2%. The largest discrepancy measured was 5% for the 3 cm field
      size and 180 kVp beam. OSLs were found to overestimate BSFs for large field sizes
      and high energies so were found to be unsuitable for BSF measurements with
      differences of up to 18%.

PMID- 30183689
TI  - SMAD4 promotes TGF-beta-independent NK cell homeostasis and maturation and
      antitumor immunity.
AB  - SMAD4 is the only common SMAD in TGF-beta signaling that usually impedes immune
      cell activation in the tumor microenvironment. However, we demonstrated here that
      selective deletion of Smad4 in NK cells actually led to dramatically reduced
      tumor cell rejection and augmented tumor cell metastases, reduced murine CMV
      clearance, as well as impeded NK cell homeostasis and maturation. This was
      associated with a downregulation of granzyme B (Gzmb), Kit, and Prdm1 in Smad4
      deficient NK cells. We further unveiled the mechanism by which SMAD4 promotes
      Gzmb expression. Gzmb was identified as a direct target of a transcriptional
      complex formed by SMAD4 and JUNB. A JUNB binding site distinct from that for
      SMAD4 in the proximal Gzmb promoter was required for transcriptional activation
      by the SMAD4-JUNB complex. In a Tgfbr2 and Smad4 NK cell-specific double
      conditional KO model, SMAD4-mediated events were found to be independent of
      canonical TGF-beta signaling. Our study identifies and mechanistically
      characterizes unusual functions and pathways for SMAD4 in governing innate immune
      responses to cancer and viral infection, as well as NK cell development.

PMID- 30183690
TI  - Distinct Anti-Fibrotic Effects of Exosomes Derived from Endothelial Colony
      Forming Cells Cultured Under Normoxia and Hypoxia.
AB  - BACKGROUND The therapeutic potential of endothelial colony-forming cells (ECFCs)
      may be impaired in an ischemic environment. Direct injection of ECFCs is not an
      effective method of rescuing the ischemic heart, but exosomes derived from these
      cells may be a promising therapeutic tool. However, exosomes produced under
      normoxia and hypoxia may not be identical. Therefore, the purpose of this study
      was to investigate alterations in the anti-fibrotic effects of hypoxia-treated
      ECFC-derived exosomes and the underlying mechanism involved. MATERIAL AND METHODS
      ECFCs were isolated from peripheral blood and exosomes were collected from ECFCs
      treated with normoxia (nor-exo) or hypoxia (hyp-exo). Effects of exosomes on
      cardiac fibroblast activation were evaluated in vitro. MicroRNAs (miRNAs) inside
      the exosomes were extracted and compared using next-generation RNA sequencing.
      Predicted target mRNAs of miR-10b-5p were validated using a dual-luciferase
      reporter gene assay method. RESULTS Nor-exo significantly ameliorated cardiac
      fibroblast activation in vitro. These effects were attenuated in the hyp-exo
      treated group. miR-10b-5p was enriched in nor-exo but not in hyp-exo. Dual
      luciferase reporter gene assay found that both SMAD-specific E3 ubiquitin protein
      ligase 1 (Smurf1) and histone deacetylase 4 (HDAC4) mRNAs were inhibited by miR
      10b-5p. The expression of neutral sphingomyelinase 2 (N-SMase2) was decreased in
      hypoxia ECFCs, and this result was consistent with the changes in miR-10b-5p in
      hyp-exo. CONCLUSIONS Due to a reduction of miR-10b-5p, which targets the fibrotic
      genes Smurf1 and HDAC4, the anti-fibrotic effects of hyp-exo were abolished.

PMID- 30183692
TI  - The Impact of Multiple Primary Rules on Cancer Statistics in Canada, 1992 to
      2012.
AB  - INTRODUCTION: Several sets of multiple primary rules have been used in Canada to
      determine whether a cancer is new and little is known of the impact on cancer
      statistics. We examine the effect of rules on the magnitude and trend of age
      standardized incidence rates (ASIRs) of cancer in Canada between 1992 and 2012.
      METHODS: Cancer- and sex-specific ASIRs were estimated using Canadian Cancer
      Registry (CCR) rules and the more conservative International Agency for Research
      on Cancer (IARC) rules. CCR- and IARC-based ASIRs and trends were compared using
      rate ratios (CCR:IARC) and joinpoint analysis, respectively. We highlight
      instances where CCR-based ASIRs exceed the upper 95% confidence limit of
      corresponding IARC-based ASIRs, as well as instances where the magnitude and/or
      direction of annual percent change (APC) in ASIRs differ across rules.
      Additionally, we examine how differences in CCR- and IARC-based estimates vary
      across regions. RESULTS: Between 1992 and 2012, ASIR ratios (CCR:IARC) for all
      cancers combined increased from about 1 to 1.061 and 1.067 for males and females,
      respectively, and reached as high as 1.141 for male melanoma and 1.109 for female
      breast cancer. Between 2010 and 2012, ASIR ratios were elevated for stage 0-1
      colorectal (males, 1.060; females, 1.072) and lung and bronchus cancer (males,
      1.052; females, 1.061) and all stages of female breast cancer (stage 0-1, 1.100;
      stage 2, 1.061; stage 3, 1.059; stage 4, 1.094). Where differences existed, CCR
      based trends tended to demonstrate steeper increases (eg, male and female
      melanoma) or less steep declines (eg, all male cancers, female breast cancer).
      Ontario was particularly impacted and substantially influenced national
      estimates. CONCLUSION: Multiple primary rules can substantially affect the
      magnitude and trend of ASIRs. The impact will continue to grow as the number of
      people surviving cancer, and thus at risk for subsequent cancers, continues to
      grow. Because of inconsistencies in the multiple primary rules used over time, we
      recommend using IARC rules for monitoring trends and making comparisons across
      jurisdictions, and using CCR rules for quantifying the full burden of cancer.

PMID- 30183691
TI  - Validating Obstructive Genitourinary Defects in an Environment of Potential
      Overdiagnosing.
AB  - INTRODUCTION: The mission of the Department of Defense Birth and Infant Health
      Registry (Registry) is to conduct ongoing surveillance of birth defects among
      military families, following the National Birth Defects Prevention Network
      (NBDPN) case definitions. From 2009 to 2011, a 30% increase in diagnoses of
      obstructive genitourinary defects (OGDs) was observed in the Registry. To explore
      the source of this finding, we identified the location with the highest increase
      and conducted a validation study for OGD cases. METHODS: The study population
      consisted of a random sample of 30 infants defined as OGD cases in the Registry
      (2010-2011), born at 1 specific military hospital. OGD cases were defined by the
      presence of the International Classification of Diseases, Ninth Revision,
      Clinical Modification (ICD-9-CM) diagnostic codes 753.2 and/or 753.6 in
      administrative claims data. A physician reviewed electronic medical records for
      each infant to confirm true OGD cases and a positive predictive value and 95% CI
      was calculated. RESULTS: Physician review confirmed only 10% (95% CI, 2%-27%) of
      the random sample of OGD cases (n = 30) from the identified hospital as true
      cases. Approximately 97% of infants in this sample were assigned the less severe
      ICD-9-CM code, 753.2. CONCLUSIONS: These results support the 2014 modifications
      to the NBDPN OGD case definition, which excluded from reporting ICD-9-CM
      diagnostic code 753.2, which is the less severe OGD diagnosis that may
      spontaneously resolve without the need for intervention and is more likely to
      increase the number of false positive cases.

PMID- 30183693
TI  - Cancers Among the Oldest Old in Massachusetts from 2004-2014.
AB  - OBJECTIVE: Describing the burden of cancer in the oldest old (those aged >=85
      years at diagnosis) is important, as the growing elderly population in
      Massachusetts lives to older ages. METHODS: Incident cases of invasive cancer in
      Massachusetts from 2004-2014 were provided by the Massachusetts Cancer Registry.
      The incidence of cancer among the oldest old was compared with the population
      aged 65-74 years and 75-84 years. Joinpoint regression was used to assess trends
      in the rates of the most common cancers in the oldest old population. RESULTS: In
      Massachusetts from 2004-2014, 7.4% of incident cancers in men and 10.2% of
      incident cancers in women were diagnosed in people aged >=85 years. The cancer
      with the highest incidence among the oldest old was lung cancer among men (473.7
      cases per 100,000) and breast cancer among women (347.0 cases per 100,000). From
      2004-2014, there were statistically significant annual decreases in prostate
      cancer and colorectal cancer among the oldest old men and women, as well as lung
      cancer among oldest old men and breast cancer among oldest old women. The oldest
      old were more likely to be diagnosed at a distant stage of prostate and breast
      cancer than people diagnosed at ages 65-74 years and ages 75-84 years.
      CONCLUSIONS: The oldest old population in Massachusetts has a different burden of
      cancer incidence than the general population, including high incidence and more
      distant-stage disease. Informing public health departments and practitioners of
      the common cancers in the population 85 and above is important to improve cancer
      care in this high comorbidity population.

PMID- 30183694
TI  - Trends in Contralateral Prophylactic Mastectomy and Other Types of Breast Cancer
      Surgery, South Carolina, 2005-2013.
AB  - BACKGROUND AND OBJECTIVES: Over the last decade, researchers have noted an
      increase in the rate of contralateral prophylactic mastectomy (CPM) across the
      United States despite the limited evidence on survival improvement associated
      with this surgery. Due to a lack of information on CPM in South Carolina, the
      authors of this study proposed to evaluate trends of different breast cancer
      surgery types with an emphasis on CPM rates. METHODS: A descriptive analysis was
      conducted regarding CPM in South Carolina among females who underwent surgery for
      breast cancer cases diagnosed from 2005-2013. The resulting data were compared
      over time with other type of surgeries performed. Data from the South Carolina
      Central Cancer Registry, a population-based cancer registry, were used to perform
      this analysis. RESULTS: Research revealed that 2,527 (7.41%) of females who were
      surgically treated for breast cancer underwent CPM. The rate increased from 4.21%
      in 2005 to 9.63% in 2013. Race differentials revealed that, for whites and
      blacks, the rates increased from 3.82% to 7.88% and from 0.3% to 1.57%,
      respectively. The non-Hispanic population CPM rate increased from 4.16% in 2005
      to 9.61% in 2013; they represented 98.42% of the total number of CPMs performed.
      For Hispanics, the CPM rate increased from 9.68% in 2005 to 11.54% in 2013. The
      unilateral mastectomy rate decreased from 26.56% in 2005 to 23.99% in 2013. The
      breast-conserving surgery rate was steady. CONCLUSION: The CPM rate increased in
      South Carolina for breast cancer cases diagnosed from 2005-2013 among blacks,
      whites, non-Hispanics, and Hispanics. Further research should be done to identify
      the risks factors for CPM among females diagnosed with breast cancer in South
      Carolina.

PMID- 30183695
TI  - Differential Reporting of In Situ Colorectal Cancer in New York State and the
      United States.
AB  - BACKGROUND: Surveillance of colorectal cancer (CRC) at all stages of diagnosis,
      including in situ, is necessary to have a complete picture of the patterns and
      trends of this disease. However, registry data suggest that the reporting of in
      situ CRC is variable. METHODS: We used SaTScan statistical software to identify
      significant clusters of unusual CRC stage distribution in New York State (NYS)
      among cases diagnosed between 2010 and 2014. These results were compared to the
      CRC stage distribution within the National Program of Cancer Registries and
      Surveillance, Epidemiology, and End Results Program (SEER) 18 registries for the
      same period. We also computed rates and trends by type of reporting source
      (hospital inpatient vs outpatient surgery center), and reviewed the opinions of
      several NYS pathologists regarding the dividing line between in situ carcinoma
      and high-grade dysplasia (HGD). RESULTS: Seven areas within NYS were identified
      as having a statistically unusual proportion of in situ cases, ranging from 4% in
      Central New York to 22% on eastern Long Island. Nationally, the percentage ranged
      from 0.4% in the Seattle-Puget Sound SEER registry to 9.2% in Maryland. Feedback
      from clinicians revealed diverse opinions about the in situ/HGD boundary.
      CONCLUSIONS: In situ CRC is being reported inconsistently within New York and the
      United States, and lacks a universally agreed-upon definition. The recent
      downward trend in in situ CRC reported in the literature may be an artifact of
      changes in reporting practices.

PMID- 30183696
TI  - Acute Stroke Registry Planning Experiences.
AB  - BACKGROUND: Stroke is a serious health threat around the world, particularly in
      developing countries. As a preventive action, disease registries have long been
      used in developed countries. Based on the globally accepted evidence, disease
      registries have an impressive positive impact on different dimensions of health
      care systems. In order to develop an acute stroke registry, acute stroke registry
      planning experiences in the world are assessed in this paper. METHODS: There were
      4 main factors in the planning phase to be assessed: determination of goal,
      scope, registration type, and consideration of technical aspects. Electronic
      databases were examined to find 27 relevant English-language articles focusing on
      acute stroke registry development. Based on the literature review, the main data
      sets and care quality measures of acute stroke registries were identified.
      RESULTS: The main purposes of developing an acute stroke registry are improvement
      of care quality, epidemiology assessment, and evaluation of health care system
      outcomes. Most of the registries focus on improving care quality. The number of
      multicenter, Web-based, and prospective registries were significantly higher than
      other types of registries. Only 1 of the registry systems implemented clinical
      support tools. Among 12 data sets identified to be considered as registry, 7 were
      highly used. Among the 14 care quality measures in acute ischemic stroke, the
      mostly used measure was the rate of early thrombolytic therapy. CONCLUSION:
      Establishment of a Web-based, prospective registry system for the acute phase of
      stroke seems useful for monitoring the rate of early thrombolytic therapy. The
      establishment of a clinical guideline-based support tool for diagnosis of
      patients' eligibility for thrombolytic treatment is suggested. As observed in
      this research, time is a very important factor in care quality improvement,
      particularly in the acute phase of stroke, for achievement of a more qualified
      care and a more serious surveillance on prehospital and hospital emergency
      systems.

PMID- 30183697
TI  - Smart Acute Stroke Quality Registry Design-Data Elements Identification.
AB  - INTRODUCTION: Stroke is one of the most important health problems around the
      world. Care quality improvement in the acute phase is significantly influential
      on stroke prognosis. An acute stroke quality registry that is integrated with a
      guideline-based support tool is a powerful system for measuring and improving
      care quality. As the first step in registry system design, the goal of this study
      was to identify relative data elements. METHODS: A list of common data elements
      taken from the National Institute of Neurological Disorders and Stroke and a list
      of data elements for paper-based medical records were first evaluated, then
      compared with each other. In parallel, a literature review was conducted to
      explore the main data elements in acute stroke registries. Considering quality
      improvement as the main purpose, a second study was undertaken to identify the
      measures of acute stroke care quality. For guideline-based smart diagnosis of
      patients' eligibility for thrombolytic treatment (as a clinical support tool),
      clinical guidelines of the American Heart Association were assessed, and
      appropriate eligibility criteria were identified. Finally, a questionnaire was
      prepared based on the identified data elements. The questionnaire was distributed
      among 17 neurology physicians for identification of essential data elements
      (minimum data sets). RESULTS: Patient-centric data elements were identified and
      classified into 3 categories: (1) data elements identified based on acute stroke
      care quality measures; (2) data elements for diagnosis of patients' eligibility
      for tissue plasminogen activator treatment based on clinical guidelines; and (3)
      essential data elements based on paper medical records. After duplication
      removal, the 3 categories of data elements were integrated. Finally, essential
      data elements were identified using the neurology clinical experts' survey.
      CONCLUSION: Compared to traditional disease registries, quality improvement
      registries cover much more detailed data elements. Integration of medical record
      data elements with care quality measures, as well as guideline-based criteria,
      results in a powerful source of data for more exact studies and analysis by
      clinical support tools. Identifying essential data elements as a mandatory part
      of the system helps with more accurate data entry, and can also be considered a
      ready-to-use item for other relative systems.

PMID- 30183698
TI  - Disentangling the role of users' preferences and impulsivity traits in
      problematic Facebook use.
AB  - The use of social network sites (SNSs) has grown dramatically. Numerous studies
      have shown that SNS users may suffer from excessive use, associated with
      addictive-like symptoms. With a focus on the popular SNS Facebook (FB), our aims
      in the current study were twofold: First, to explore the heterogeneity of FB
      usage and determine which kind of FB activity predicts problematic usage; second,
      to test whether specific impulsivity facets predict problematic use of FB. To
      this end, a sample of FB users (N = 676) completed an online survey assessing
      usage preferences (e.g., types of activities performed), symptoms of problematic
      FB use and impulsivity traits. Results indicated that specific usage preferences
      (updating one's status, gaming via FB, and using notifications) and impulsive
      traits (positive and negative urgency, lack of perseverance) are associated to
      problematic FB use. This study underscores that labels such as FB "addiction" are
      misleading and that focusing on the actual activities performed on SNSs is
      crucial when considering dysfunctional usage. Furthermore, this study clarified
      the role of impulsivity in problematic FB use by building on a theoretically
      driven model of impulsivity that assumes its multidimensional nature. The current
      findings have identifiable theoretical and public health implications.

PMID- 30183699
TI  - Entrepreneurship, intrapreneurship and scientific mobility: The Spanish case.
AB  - Scientific mobility can stimulate entrepreneurship and intrapreneurship, acting
      as a catalyst for reducing imbalances between local and global science and the
      resulting socio-economic damage. This study evaluates both whether scientific
      mobility effectively promotes these concepts and the fundamental reasons to
      articulate effective policies for scientific mobility. Toward this end, a survey
      has been prepared following the methodology of Global Entrepreneurship Monitor
      (GEM) and current scientific literature. A total of 364 researchers involved in
      Spanish scientific mobility took part in the study: Spanish scientists abroad
      (135) and scientists returned to Spain (52), as mobile groups, and young
      researchers in Spain (177), as a group of scientists who could go abroad, but
      that have not yet begun to leave. The results demonstrate that scientific
      mobility does promote entrepreneurship and, especially intrapreneurship.
      Moreover, since permanent positions are scarce for these groups and their
      mobility decisions largely depend on job opportunities, the involved Spanish
      authorities and agents can improve scientific mobility by means suitable policies
      that make the most of this potential to the benefit of economic growth and job
      creation.

PMID- 30183700
TI  - Schadenfreude and the spread of political misfortune.
AB  - Schadenfreude is a social emotion that describes one's happiness at the
      misfortune of others. Because people experience schadenfreude to different
      extents, it can also be considered a trait. The present research aimed to develop
      a trait measure of schadenfreude and investigate the relationship between
      schadenfreude and political downfalls. We developed an item pool and used
      exploratory (Study 1) and confirmatory (Study 2) factor analyses to establish a
      12-item, two-factor schadenfreude measure: benign and malicious. We also assessed
      its test-retest reliability (Study 3) and convergent validity with related
      measures (Study 4). Findings supported a two-factor schadenfreude measure that
      produced valid and reliable scores (Studies 1-4). In an experiment, we found a
      positive correlation between episodic-but not trait-schadenfreude on spreading
      news of a politician's downfall (Study 5). Using a 3 (Political affiliation:
      Democrat, Republican, or other) * 3 (Manipulated condition: Democrat, Republican,
      or CEO) design, we examined the extent to which participants' schadenfreude
      predicted their intentions and choices to share an embarrassing news story about
      a politician or CEO via social media. Schadenfreude can be assessed as a reliable
      trait-one that may help us predict why some people intend to spread news of
      embarrassing political failures.

PMID- 30183702
TI  - Research on the forward-looking behavior judgment of heating oil price evolution
      based on complex networks.
AB  - Analyzing and predicting the trend of price fluctuation has been receiving more
      and more attention, as price risk has become the focus of risk control research
      in heating oil futures market. A novel time series prediction model combined with
      the complex network method is put forward in the paper. First of all, this paper
      counts the cumulative time interval of different nodes in the network, and fits
      its growth trend with the Fourier model. Then a novel price fluctuation
      prediction model is established based on the effective information such as some
      topology properties extracted from the network. The results show that the Fourier
      model can predict the emergence time of new nodes in the next stage, and the
      established price fluctuation prediction model can infer the names of nodes in
      the prediction interval, so as to determine the forward-looking behavior of price
      evolution. Besides, liken to the NAR neural network, the prediction results
      obtained by the proposed method also show superiority, which has important
      theoretical value and academic significance for early warning and prediction of
      price behavior in the heating oil futures market.

PMID- 30183701
TI  - Red cell distribution width at hospital discharge and out-of hospital outcomes in
      critically ill non-cardiac vascular surgery patients.
AB  - OBJECTIVE: Red cell distribution width (RDW) is associated with mortality and
      bloodstream infection risk in the critically ill. In vascular surgery patients
      surviving critical care it is not known if RDW can predict subsequent risk of all
      cause mortality following hospital discharge. We hypothesized that an increase in
      RDW at hospital discharge in vascular surgery patients who received critical care
      would be associated with increased mortality following hospital discharge.
      DESIGN, SETTING, AND PARTICIPANTS: We performed a two-center observational cohort
      study of critically ill non-cardiac vascular surgery patients surviving admission
      18 years or older treated between November, 1997, and December 2012 in Boston,
      Massachusetts. EXPOSURES: RDW measured within 24 hours of hospital discharge and
      categorized a priori as <=13.3%, 13.3-14.0%, 14.0-14.7%, 14.7-15.8%, >15.8%. MAIN
      OUTCOMES AND MEASURES: The primary outcome was all cause mortality in the 90 days
      following hospital discharge. RESULTS: The cohort included 4,715 patients (male
      58%; white 83%; mean age 62.9 years). 90 and 365-day post discharge mortality was
      7.5% and 14.4% respectively. In the cohort, 47.3% were discharged to a care
      facility and 14.8% of patients were readmitted within 30 days. After adjustment
      for age, gender, race, Deyo-Charlson comorbidity Index, patient type, acute organ
      failures, prior vascular surgery and vascular surgery category, patients with a
      discharge RDW 14.7-15.8% or >15.8% have an adjusted OR of 90-day post discharge
      mortality of 2.52 (95%CI, 1.29-4.90; P = 0.007) or 5.13 (95%CI, 2.70-9.75; P
      <0.001) relative to patients with a discharge RDW <=13.3%. The adjusted odds of
      30-day readmission in the RDW >15.8% group was 1.52 (95%CI, 1.12-2.07; P = 0.007)
      relative to patients with a discharge RDW <=13.3%. Similar adjusted discharge RDW
      outcome associations are present at 365 days following hospital discharge and for
      discharge to a care facility. CONCLUSIONS: In critically ill vascular surgery
      patients who survive hospitalization, an elevated RDW at hospital discharge is a
      strong predictor of subsequent mortality, hospital readmission and placement in a
      care facility. Patients with elevated RDW are at high risk for adverse out of
      hospital outcomes and may benefit from closer post discharge follow-up and higher
      intensity rehabilitation.

PMID- 30183703
TI  - Transcriptome analysis of Polianthes tuberosa during floral scent formation.
AB  - Polianthes tuberosa is a popular ornamental plant. Its floral scent volatiles
      mainly consist of terpenes and benzenoids that emit a charming fragrance.
      However, our understanding of the molecular mechanism responsible for the floral
      scent of P. tuberosa is limited. Using transcriptome sequencing and de novo
      assembly, a total of 228,706,703 high-quality reads were obtained, which resulted
      in the identification of 96,906 unigenes (SRA Accession Number SRP126470, TSA
      Acc. No. GGEA00000000). Approximately 41.85% of the unigenes were functionally
      annotated using public databases. A total of 4,694 differentially expressed genes
      (DEGs)were discovered during flowering. Gas chromatography-mass spectrometry
      analysis revealed that the majority of the volatiles comprised benzenoids and
      small amounts of terpenes. Homology analysis identified 13 and 17 candidate genes
      associated with terpene and benzenoid biosynthesis, respectively. Among these,
      PtTPS1, PtDAHPSs, PtPAL1, and PtBCMT2 might play important roles in regulating
      the formation of floral volatiles. The data generated by transcriptome sequencing
      provide a critical resource for exploring concrete characteristics as well as for
      supporting functional genomics studies. The results of the present study also lay
      the foundation for the elucidation of the molecular mechanism underlying the
      regulation of floral scents in monocots.

PMID- 30183705
TI  - Balancing effort and benefit of K-means clustering algorithms in Big Data realms.
AB  - In this paper we propose a criterion to balance the processing time and the
      solution quality of k-means cluster algorithms when applied to instances where
      the number n of objects is big. The majority of the known strategies aimed to
      improve the performance of k-means algorithms are related to the initialization
      or classification steps. In contrast, our criterion applies in the convergence
      step, namely, the process stops whenever the number of objects that change their
      assigned cluster at any iteration is lower than a given threshold. Through
      computer experimentation with synthetic and real instances, we found that a
      threshold close to 0.03n involves a decrease in computing time of about a factor
      4/100, yielding solutions whose quality reduces by less than two percent. These
      findings naturally suggest the usefulness of our criterion in Big Data realms.

PMID- 30183704
TI  - Galleria mellonella as an insect model for P. destructans, the cause of White
      nose Syndrome in bats.
AB  - Pseudogymnoascus destructans is the fungal pathogen responsible for White-nose
      Syndrome (WNS), a disease that has killed millions of bats in North America over
      the last decade. A major obstacle to research on P. destructans has been the lack
      of a tractable infection model for monitoring virulence. Here, we establish a
      high-throughput model of infection using larvae of Galleria mellonella, an
      invertebrate used to study host-pathogen interactions for a wide range of
      microbial species. We demonstrate that P. destructans can kill G. mellonella
      larvae in an inoculum-dependent manner when infected larvae are housed at 13
      degrees C or 18 degrees C. Larval killing is an active process, as heat-killed P.
      destructans spores caused significantly decreased levels of larval death compared
      to live spores. We also show that fungal spores that were germinated prior to
      inoculation were able to kill larvae 3-4 times faster than non-germinated spores.
      Lastly, we identified chemical inhibitors of P. destructans and used G.
      mellonella to evaluate these inhibitors for their ability to reduce virulence. We
      demonstrate that amphotericin B can effectively block larval killing by P.
      destructans and thereby establish that this infection model can be used to screen
      biocontrol agents against this fungal pathogen.

PMID- 30183707
TI  - Nighttime lights as a proxy for human development at the local level.
AB  - Nighttime lights, calculated from weather satellite recordings, are increasingly
      used by social scientists as a proxy for economic activity or economic
      development in subnational regions of developing countries where disaggregated
      data from statistical offices are not available. However, so far, our
      understanding of what nighttime lights capture in these countries is limited. We
      use geo-referenced Demographic and Health Surveys (DHS) from 29 African countries
      to construct indicators of household wealth, education and health for DHS cluster
      locations as well as for grid cells of roughly 50 * 50 km. We show that nighttime
      lights are positively associated with these location-specific indicators of human
      development, and that the variation in nighttime lights can explain a substantial
      share in the variation in these indicators. We conclude that nighttime lights are
      a good proxy for human development at the local level.

PMID- 30183706
TI  - Breast cancer subtype and survival among Indigenous American women in Peru.
AB  - Latina women in the U.S. have relatively low breast cancer incidence compared to
      Non-Latina White (NLW) or African American women but are more likely to be
      diagnosed with the more aggressive "triple negative" breast cancer (TNBC).
      Latinos in the U.S. are a heterogeneous group originating from different
      countries with different cultural and ancestral backgrounds. Little is known
      about the distribution of tumor subtypes in Latin American regions. Clinical
      records of 303 female Peruvian patients, from the Peruvian National Cancer
      Institute, were analyzed. Participants were diagnosed with invasive breast cancer
      between 2010 and 2015 and were identified as residing in either the Selva or
      Sierra region. We used Fisher's exact test for proportions and multivariable Cox
      Proportional Hazards Models to compare overall survival between regions. Women
      from the Selva region were more likely to be diagnosed with TNBC than women from
      the Sierra region (31% vs. 14%, p = 0.01). In the unadjusted Cox model, the
      hazard of mortality was 1.7 times higher in women from the Selva than the Sierra
      (p = 0.025); this survival difference appeared to be largely explained by
      differences in the prevalence of TNBC. Our results suggest that the distribution
      of breast cancer subtypes differs between highly Indigenous American women from
      two regions of Peru. Disentangling the factors that contribute to this difference
      will add valuable information to better target prevention and treatment efforts
      in Peru and improve our understanding of TNBC among all women. This study
      demonstrates the need for larger datasets of Latin American patients to address
      differences between Latino subpopulations and optimize targeted prevention and
      treatment.

PMID- 30183708
TI  - Conservation tillage increases carbon sequestration of winter wheat-summer maize
      farmland on Loess Plateau in China.
AB  - The idea of mitigating anthropogenic CO2 emissions by increasing soil organic
      carbon (SOC) is notable. However, the estimation of the net ecosystem carbon
      balance after conversion from conventional tillage to conservational tillage has
      been poorly quantified for the Loess Plateau in China. A 2-year field experiment
      was conducted to estimate the agroecosystem carbon balance of a winter wheat
      summer maize rotation system using a full carbon cycle analysis. The results
      showed that a positive net ecosystem carbon balance value in the cases of rotary
      tillage with straw incorporation, chisel plow tillage with straw incorporation,
      and no tillage with straw mulching treatments. Note that a negative value was
      detected for the conventional moldboard plowing tillage without crop straw
      treatment. The conversion from conventional tillage to conservational tillage
      substantially enhanced the carbon sink potential from 0.84 t C ha-1 yr-1 to 2.69
      t C ha-1 yr-1 in both years. Our findings suggest that the expansion of
      conservational tillage could enhance the potential carbon sink of the rain-fed
      land in China.

PMID- 30183709
TI  - Effects of supplementary feeding on interspecific dominance hierarchies in garden
      birds.
AB  - Individuals often differ in competitive ability, which can lead to the formation
      of a dominance hierarchy that governs differential access to resources. Previous
      studies of dominance have predominently focussed on within-species interactions,
      while the drivers of between-species competitive hierarchies are poorly
      understood. The increasing prevalence of predictable anthropogenic food
      subsidies, such as that provided by garden bird feeders, is likely to intensify
      between-species competition. However, the consequences for resource acquisition
      await detailed study, and in particular, whether competitive interactions are
      influenced by food quality is not known. Here, we examine competitive
      interactions amongst ten passerine species of birds utilising supplementary food
      sources of differing quality. We show that dominance rank is strongly predicted
      by body mass across species. Socially dominant, heavier species monopolised
      access to a food that had a relatively short handling time (sunflower hearts),
      spent longer on supplementary feeders, and pecked at lower rates. In contrast
      subordinate, lighter species were constrained to feed on a food that had a
      relatively long handling time (sunflower seeds with the hull intact). Our
      findings suggest that differences in body mass may result in between-species
      dominance hierarchies that place the heaviest species in the greatest control of
      supplementary feeding sites, gaining superior access to higher value foods. This
      may have important implications for the use of supplementary feeding as a
      conservation tool.

PMID- 30183710
TI  - Can we learn to manage stress? A randomized controlled trial carried out on
      university students.
AB  - : In our research, we examined the efficacy of an Internet-based stress
      management program. Our interest in evaluating this type of intervention is based
      on the increasing accessibility of the Internet today, the growth of Internet
      based interventions for various psychopathological problems, and the observation
      that despite the prevalence of stress among university students, only a fraction
      of students ever seek professional help. METHODOLOGY: "I'm managing my stress"
      ("Je gere mon stresse"), an Internet-based self-help program composed of four
      sessions, was examined in this study. The aforementioned program is based on
      cognitive-behavioral therapy and was inspired by the "Funambule" program in
      Quebec. Four questionnaires (Perceived Stress Scale, Rosenberg Self-Esteem Scale,
      Scale of Satisfaction in Studies, and General Health Questionnaire) uploaded
      online were answered thrice: during "preintervention", "postintervention", and
      "follow-up" stages, the latter of which occurred three months after the
      intervention. The sample comprised 128 university students, with the majority
      being women (81.25%). The subjects were divided randomly into two groups (an
      experimental group and a control group that did not follow the program). RESULTS:
      The self-esteem scores of the control group were significantly higher than those
      of the experimental group at the preintervention stage, but this difference
      disappeared at the postintervention and follow-up stages. There were also
      significantly lower scores on the General Health Questionnaire subfactors of
      somatic symptoms and anxiety/insomnia in the experimental group than in the
      control group during the postintervention stage, though no differences were
      observed before the intervention. These differences no longer remained after
      three months. ANOVA revealed significant effects of the intervention over time in
      the experimental group. Effects were observed at both the postintervention and
      follow-up stages for self-esteem, perceived stress, satisfaction in studies, and
      in the somatic symptoms, anxiety and insomnia and severe depression aspects of
      the General Health Questionnaire (Cohen's d = 0.38 to 4.58). In contrast, no
      effects were observed in the control group. CONCLUSION: This type of Internet
      based program has the ability to reach a large number of students due to its
      rather short format and accessibility. It has already shown improvements in terms
      of the levels of perceived stress, psychological distress and satisfaction with
      studies. The option of online interventions could appeal specifically to students
      who do not seek professional help. However, even though these results are
      promising at the postintervention stage, they are limited, as indicated by the
      lack of significant differences between the two groups after the initial three
      months of follow-up. We still, specifically, need to improve this intervention
      program and, generally, need more research to address the methodological problems
      raised by this type of intervention. TRIAL REGISTRATION: ISRCTN registry,
      ISRCTN13709272.

PMID- 30183711
TI  - Considering parental hearing status as a social determinant of deaf population
      health: Insights from experiences of the "dinner table syndrome".
AB  - The influence of early language and communication experiences on lifelong health
      outcomes is receiving increased public health attention. Most deaf children have
      non-signing hearing parents, and are at risk for not experiencing fully
      accessible language environments, a possible factor underlying known deaf
      population health disparities. Childhood indirect family communication-such as
      spontaneous conversations and listening in the routine family environment (e.g.
      family meals, recreation, car rides)-is an important source of health-related
      contextual learning opportunities. The goal of this study was to assess the
      influence of parental hearing status on deaf people's recalled access to
      childhood indirect family communication. We analyzed data from the Rochester Deaf
      Health Survey-2013 (n = 211 deaf adults) for associations between
      sociodemographic factors including parental hearing status, and recalled access
      to childhood indirect family communication. Parental hearing status predicted
      deaf adults' recalled access to childhood indirect family communication (chi2 =
      31.939, p < .001). The likelihood of deaf adults reporting "sometimes to never"
      for recalled comprehension of childhood family indirect communication increased
      by 17.6 times for those with hearing parents. No other sociodemographic or deaf
      specific factors in this study predicted deaf adults' access to childhood
      indirect family communication. This study finds that deaf people who have hearing
      parents were more likely to report limited access to contextual learning
      opportunities during childhood. Parental hearing status and early childhood
      language experiences, therefore, require further investigation as possible social
      determinants of health to develop interventions that improve lifelong health and
      social outcomes of the underserved deaf population.

PMID- 30183712
TI  - Organellar genome analysis reveals endosymbiotic gene transfers in tomato.
AB  - We assembled three complete mitochondrial genomes (mitogenomes), two of Solanum
      lycopersicum and one of Solanum pennellii, and analyzed their intra- and
      interspecific variations. The mitogenomes were 423,596-446,257 bp in length.
      Despite numerous rearrangements between the S. lycopersicum and S. pennellii
      mitogenomes, over 97% of the mitogenomes were similar to each other. These
      mitogenomes were compared with plastid and nuclear genomes to investigate genetic
      material transfers among DNA-containing organelles in tomato. In all mitogenomes,
      9,598 bp of plastome sequences were found. Numerous nuclear copies of
      mitochondrial DNA (NUMTs) and plastid DNA (NUPTs) were observed in the S.
      lycopersicum and S. pennellii nuclear genomes. Several long organellar DNA
      fragments were tightly clustered in the nuclear genome; however, the NUMT and
      NUPT locations differed between the two species. Our results demonstrate the
      recent occurrence of frequent endosymbiotic gene transfers in tomato genomes.

PMID- 30183713
TI  - Understanding meta-population trends of the Australian fur seal, with insights
      for adaptive monitoring.
AB  - Effective ecosystem-based management requires estimates of abundance and
      population trends of species of interest. Trend analyses are often limited due to
      sparse or short-term abundance estimates for populations that can be logistically
      difficult to monitor over time. Therefore it is critical to assess regularly the
      quality of the metrics in long-term monitoring programs. For a monitoring program
      to provide meaningful data and remain relevant, it needs to incorporate
      technological improvements and the changing requirements of stakeholders, while
      maintaining the integrity of the data. In this paper we critically examine the
      monitoring program for the Australian fur seal (AFS) Arctocephalus pusillus
      doriferus as an example of an ad-hoc monitoring program that was co-ordinated
      across multiple stakeholders as a range-wide census of live pups in the Austral
      summers of 2002, 2007 and 2013. This 5-yearly census, combined with historic
      counts at individual sites, successfully tracked increasing population trends as
      signs of population recovery up to 2007. The 2013 census identified the first
      reduction in AFS pup numbers (14,248 live pups, -4.2% change per annum since
      2007), however we have limited information to understand this change. We analyse
      the trends at breeding colonies and perform a power analysis to critically
      examine the reliability of those trends. We then assess the gaps in the
      monitoring program and discuss how we may transition this surveillance style
      program to an adaptive monitoring program than can evolve over time and achieve
      its goals. The census results are used for ecosystem-based modelling for
      fisheries management and emergency response planning. The ultimate goal for this
      program is to obtain the data we need with minimal cost, effort and impact on the
      fur seals. In conclusion we identify the importance of power analyses for
      interpreting trends, the value of regularly assessing long-term monitoring
      programs and proper design so that adaptive monitoring principles can be applied.

PMID- 30183714
TI  - Bright paint makes interior-space surfaces appear farther away.
AB  - Previous studies have reported that bright ceilings appear higher than dark
      ceilings, irrespective of the other colorimetric properties of the ceiling color
      (hue, saturation) and irrespective of the luminance of the remaining room
      surfaces (walls, floor). In the present study, we expand these findings to width
      and depth estimates. We presented stereoscopic full-scale room simulations on a
      head-mounted display and varied the luminance of the side walls, rear wall, and
      ceiling independently of each other. Participants judged the width and depth of
      the simulated rooms. Our results show that the perceived spatial layout of a
      given room is significantly influenced by the luminance of the direct bounding
      surfaces (e.g., the side walls when judging perceived width) but less affected by
      the luminance of the other surfaces. In the discussion, we provide an overall
      picture of effects of surface luminance on the perceived layout of interior
      spaces and discuss the conclusions in the context of existing interior-design
      guidelines.

PMID- 30183715
TI  - SAS score: Targeting high-specificity for efficient population-wide monitoring of
      obstructive sleep apnea.
AB  - PROPOSAL: This paper investigates a novel screening tool for Obstructive Sleep
      Apnea Syndrome (OSAS), which aims at efficient population-wide monitoring. To
      this end, we introduce SASscore which provides better OSAS prediction specificity
      while maintaining a high sensitivity. METHODS: We process a cohort of 2595
      patients from 4 sleep laboratories in Western Romania, by recording over 100
      sleep, breathing, and anthropometric measurements per patient; using this data,
      we compare our SASscore with state of the art scores STOP-Bang and NoSAS through
      area under curve (AUC), sensitivity, specificity, negative predictive value
      (NPV), and positive predictive value (PPV). We also evaluate the performance of
      SASscore by considering different Apnea-Hypopnea Index (AHI) diagnosis cut-off
      points and show that custom refinements are possible by changing the score's
      threshold. RESULTS: SASscore takes decimal values within the interval (2, 7) and
      varies linearly with AHI; it is based on standardized measures for BMI, neck
      circumference, systolic blood pressure and Epworth score. By applying the STOP
      Bang and NoSAS questionnaires, as well as the SASscore on the patient cohort, we
      respectively obtain the AUC values of 0.69 (95% CI 0.66-0.73, p < 0.001), 0.66
      (95% CI 0.63-0.68, p < 0.001), and 0.73 (95% CI 0.71-0.75, p < 0.001), with
      sensitivities values of 0.968, 0.901, 0.829, and specificity values of 0.149,
      0.294, 0.359, respectively. Additionally, we cross-validate our score with a
      second independent cohort of 231 patients confirming the high specificity and
      good sensitivity of our score. When raising SASscore's diagnosis cut-off point
      from 3 to 3.7, both sensitivity and specificity become roughly 0.6. CONCLUSIONS:
      In comparison with the existing scores, SASscore is a more appropriate screening
      tool for monitoring large populations, due to its improved specificity. Our score
      can be tailored to increase either sensitivity or specificity, while balancing
      the AUC value.

PMID- 30183716
TI  - Interaction among susceptibility genotypes of PARP1 SNPs in thyroid carcinoma.
AB  - Polymorphisms in DNA repair genes may alter the repair mechanism which makes the
      person susceptible to DNA damage. Polymorphic variants in these DNA repair
      pathway genes such as Poly (ADP-ribose) polymerase- 1 (PARP1) have been
      associated with susceptibility of several types of cancer including thyroid. Many
      studies have been published on PARP1 gene polymorphisms and carcinogenesis with
      inconsistent results. The present study was designed to explore the link between
      the PARP1 polymorphisms and thyroid cancer risk. This case-control study was
      comprised of 456 thyroid cancer patients and 400 healthy controls. Three SNPs of
      PARP1 gene; rs1136410, rs1805414 and rs1805404 were analyzed using ARMS-PCR. The
      combined genotype and haplotype analysis were performed using haploview software
      4.2. Major allele homozygote (CC) of rs1136410 and combined genotype (TT+TC) of
      rs180414 showed a significant association with thyroid cancer risk (OR = 1.30;
      95% CI 0.99-1.77; P = 0.05) and (OR = 0.43; 95% CI = 0.27-0.67; P = 0.03).
      Histological subtype analysis showed the significant association of selected
      PARP1 SNPs with papillary, follicular and anaplastic subtypes in thyroid cancer
      patients. Haplotype analysis showed that TCT (p = 0.01), CTT (p = 0.02) and CTC
      (p = 0.03) were significantly higher in controls when compared to cases. However,
      TTC (p = 0.05) and TCC (p = 0.01) haplotype frequency was significantly higher in
      cases compared to controls. Global haplotype analysis showed that there was an
      overall significant difference between cases and controls (p = 0.001).
      Identification of these genetic risk markers may provide evidence for exploring
      insight into mechanisms of pathogenesis and subsequently aid in developing novel
      therapeutic strategies for thyroid cancer.

PMID- 30183717
TI  - From Svalbard to Siberia: Passerines breeding in the High Arctic also endure the
      extreme cold of the Western Steppe.
AB  - Few species are adapted to high latitudes, and many over-winter in milder
      climates with migrations involving extensive barrier crossings. By escaping
      extreme conditions for the majority of the year, physiological and behavioural
      adaptations presumably need to be less pronounced. The snow bunting Plectrophenax
      nivalis is the most northerly breeding passerine. We tracked the Svalbard
      population using geolocators to reveal that these individuals not only breed in
      environmental extremes, but also spend the winters in the severe cold and highly
      stochastic weather conditions of the Siberian steppe. Migratory strategies
      appeared to be flexible between individuals and years. However, common wintering
      grounds in the Asian Western Steppe were identified, where birds could utilise
      vast crop- and grasslands while enduring low ambient temperatures. The timing of
      significant long distance movements was consistent among individuals, and the
      autumn routing of the >1000 km open water flight to Novaya Zemlya incurred
      favourable wind assistance and lower risk of precipitation, compared to the
      shorter route between Svalbard and Norway used in spring. Presumably, Svalbard
      snow buntings are physiologically well-adapted to extreme conditions and their
      migration, rather being a retreat from physiologically demanding conditions,
      allows utilisation of an abundance of resources in the Asian Steppe.

PMID- 30183719
TI  - Sight-over-sound judgments of music performances are replicable effects with
      limited interpretability.
AB  - Virtuosi impress audiences with their musical expressivity and with their
      theatrical flair. How do listeners use this auditory and visual information to
      judge performance quality? Both musicians and laypeople report a belief that
      sound should trump sight in the judgment of music performance, but surprisingly,
      their actual judgments reflect the opposite pattern. In a recent study, when
      presented with 6-second videos of music competition performers, listeners
      accurately guessed the winners only when the videos were muted. Here, we
      successfully replicate this finding in a highly-powered sample but then
      demonstrate that the sight-over-sound effect holds only under limited conditions.
      When using different videos from comparable performances, in a forced-choice
      task, listeners' judgments were at or below chance. And when differences in
      performance quality were made clearer, listeners' judgments were most accurate
      when they could hear the music-without audio, performance was at chance. Sight
      therefore does not necessarily trump sound in the judgment of music performance.

PMID- 30183718
TI  - Barriers to supportive care during the Ebola virus disease outbreak in West
      Africa: Results of a qualitative study.
AB  - BACKGROUND: During the 2013-2016 West Africa Ebola outbreak, supportive care was
      the only non-experimental treatment option for patients with Ebola virus disease
      (EVD). However, providing care that would otherwise be routine for most clinical
      settings in the context of a highly contagious and lethal pathogen is much more
      challenging. The objective of this study was to document and deepen understanding
      of barriers to provision of supportive care in Ebola treatment units (ETUs) as
      perceived by those involved in care delivery during the outbreak. METHODS: This
      qualitative study consisted of 29 in-depth semi-structured interviews with
      stakeholders (decision-makers, physicians, nurses) involved in patient care
      delivery during the outbreak. Analysis consisted of interview debriefing and team
      based transcript coding in NVivo10 software using thematic analysis. FINDINGS:
      Participants emphasized three interconnected barriers to providing high-quality
      supportive care during the outbreak: 1) lack of material and human resources in
      ETUs; 2) ETU organizational structure limiting the provision of supportive
      clinical care; and 3) delayed and poorly coordinated policies limiting the
      effectiveness of global and national responses. Participants also noted the
      ethical complexities of defining and enacting best clinical practices in low
      income countries. They noted tension between, on one hand, scaling up minimal
      care and investing in clinical care preparedness to a level sustainable in West
      Africa and, on the other, providing a higher level of supportive care, which in
      low-resource health systems would require important investments. CONCLUSION: Our
      findings identified potentially modifiable barriers to the delivery of supportive
      care to patients with EVD in West Africa. Addressing these in the inter-outbreak
      period will be useful to improve patient care and outcomes during inevitable
      future outbreaks. Promoting community trust and engagement through long-term
      capacity building of the healthcare workforce and infrastructure would increase
      both health system resilience and ability to handle other outbreaks of emerging
      diseases.

PMID- 30183720
TI  - Socioeconomic inequalities and determinants of maternal health services in
      Shaanxi Province, Western China.
AB  - Prenatal health care interventions are effective ways to improve maternal and
      neonatal health. There have been few large investigations conducted on the
      inequalities in maternal health services utilization in Shaanxi Province of west
      China since the health care reform in 2009. This study examined the inequalities
      and determinants of maternal health services utilization in Shaanxi Province. A
      household survey was conducted from August to November in 2013. By using a
      multistage sampling method, local women aged 15-49 who had given birth in the
      preceding three years were recruited. Information including social-demographic
      characteristics and maternal health services utilization was collected through a
      face-to-face interview. A concentration index approach was used to measure
      inequalities in maternal health services utilization. A logistic regression model
      was employed to investigate the determinants of maternal health services
      utilization. There were 8,488 women from urban areas and 18,724 women from rural
      areas enrolled in this study. The concentration index for all the indicators of
      maternal health services utilization showed significance in these two areas. In
      urban areas, the concentration index of having 5 or more prenatal visits,
      receiving the first prenatal visit within 12 weeks, delivering at secondary- or
      higher-level health facilities and delivering by C-section were 0.0356, 0.0166,
      0.0177 and 0.0591, respectively, while in rural areas, the corresponding figures
      were 0.0385, 0.0183, 0.0334 and 0.0566, respectively. The determinants related to
      maternal health services utilization were women's age at delivery, educational
      level, employment status, parity, health problems during pregnancy and household
      income. Inequalities in maternal health services utilization still exist in
      Shaanxi Province. Providing maternal health services for younger, less educated,
      unemployed, high parity and poorer women, especially in rural areas, is expected
      to reduce the inequalities in maternal health services utilization.

PMID- 30183722
TI  - Joint bayesian convolutional sparse coding for image super-resolution.
AB  - We propose a convolutional sparse coding (CSC) for super resolution (CSC-SR)
      algorithm with a joint Bayesian learning strategy. Due to the unknown parameters
      in solving CSC-SR, the performance of the algorithm depends on the choice of the
      parameter. To this end, a coupled Beta-Bernoulli process is employed to infer
      appropriate filters and sparse coding maps (SCM) for both low resolution (LR)
      image and high resolution (HR) image. The filters and the SCMs are learned in a
      joint inference. The experimental results validate the advantages of the proposed
      approach over the previous CSC-SR and other state-of-the-art SR methods.

PMID- 30183721
TI  - Validation of diffusion tensor imaging measures of nigrostriatal neurons in
      macaques.
AB  - OBJECTIVE: Interpretation of diffusion MRI in the living brain requires
      validation against gold standard histological measures. We compared diffusion
      values of the nigrostriatal tract to PET and histological results in non-human
      primates (NHPs) with varying degrees of unilateral nigrostriatal injury induced
      by MPTP, a toxin selective for dopaminergic neurons. METHODS: Sixteen NHPs had
      MRI and PET scans of three different presynaptic radioligands and blinded video
      based motor ratings before and after unilateral carotid artery infusion of
      variable doses of MPTP. Diffusion measures of connections between midbrain and
      striatum were calculated. Then animals were euthanized to quantify striatal
      dopamine concentration, stereologic measures of striatal tyrosine hydroxylase
      (TH) immunostained fiber density and unbiased stereologic counts of TH stained
      nigral cells. RESULTS: Diffusion measures correlated with MPTP dose, nigral TH
      positive cell bodies and striatal TH-positive fiber density but did not correlate
      with in vitro nigrostriatal terminal field measures or in vivo PET measures of
      striatal uptake of presynaptic markers. Once nigral TH cell count loss exceeded
      50% the stereologic terminal field measures reached a near zero floor effect but
      the diffusion measures continued to correlate with nigral cell counts.
      CONCLUSION: Diffusion measures in the nigrostriatal tract correlate with nigral
      dopamine neurons and striatal fiber density, but have the same relationship to
      terminal field measures as a previous report of striatal PET measures of
      presynaptic neurons. These diffusion measures have the potential to act as non
      invasive index of the severity of nigrostriatal injury. Diffusion imaging of the
      nigrostriatal tract could potentially have diagnostic value in humans with
      Parkinson disease or related disorders.

PMID- 30183723
TI  - Repeated cyclone events reveal potential causes of sociality in coral-dwelling
      Gobiodon fishes.
AB  - Social organization is a key factor influencing a species' foraging and
      reproduction, which may ultimately affect their survival and ability to recover
      from catastrophic disturbance. Severe weather events such as cyclones can have
      devastating impacts to the physical structure of coral reefs and on the abundance
      and distribution of its faunal communities. Despite the importance of social
      organization to a species' survival, relatively little is known about how major
      disturbances such as tropical cyclones may affect social structures or how
      different social strategies affect a species' ability to cope with disturbance.
      We sampled group sizes and coral sizes of group-forming and pair-forming species
      of the Gobiid genus Gobiodon at Lizard Island, Great Barrier Reef, Australia,
      before and after two successive category 4 tropical cyclones. Group sizes of
      group-forming species decreased after each cyclone, but showed signs of recovery
      four months after the first cyclone. A similar increase in group sizes was not
      evident in group-forming species after the second cyclone. There was no change in
      mean pair-forming group size after either cyclone. Coral sizes inhabited by both
      group- and pair-forming species decreased throughout the study, meaning that
      group-forming species were forced to occupy smaller corals on average than before
      cyclone activity. This may reduce their capacity to maintain larger group sizes
      through multiple processes. We discuss these patterns in light of two non
      exclusive hypotheses regarding the drivers of sociality in Gobiodon, suggesting
      that benefits of philopatry with regards to habitat quality may underpin the
      formation of social groups in this genus.

PMID- 30183724
TI  - Stoichiometry, polarity, and organometallics in solid-phase extracted dissolved
      organic matter of the Elbe-Weser estuary.
AB  - Dissolved organic matter (DOM) is ubiquitous in natural waters and plays a
      central role in the biogeochemistry in riverine, estuarine and marine
      environments. This study quantifies and characterizes solid-phase extractable DOM
      and trace element complexation at different salinities in the Weser and Elbe
      River, northern Germany, and the North Sea. Dissolved organic carbon (DOC), total
      dissolved nitrogen (TDN), Co and Cu concentrations were analyzed in original
      water samples. Solid-phase extracted (SPE) water samples were analyzed for DOC
      (DOCSPE), dissolved organic nitrogen (DONSPE), sulfur (DOSSPE) and trace metal
      (51V, 52Cr, 59Co, 60Ni, 63Cu, 75As) concentrations. Additionally, different pre
      treatment conditions (acidification vs. non-acidification prior to SPE) were
      tested. In agreement with previous studies, acidification led to generally higher
      recoveries for DOM and trace metals. Overall, higher DOM and trace metal
      concentrations and subsequently higher complexation of trace metals with carbon
      and sulfur-containing organic complexes were found in riverine compared to marine
      samples. With increasing salinity, the concentrations of DOM decreased due to
      estuarine mixing. However, the slightly lower relative decrease of both, DOCSPE
      and DONSPE (~77%) compared to DOSSPE (~86%) suggests slightly faster removal
      processes for DOSSPE. A similar distribution of trace metal and carbon and sulfur
      containing DOM concentrations with salinity indicates complexation of trace
      metals with organic ligands. This is further supported by an increase in Co and
      Cu concentration after oxidation of organic complexes by UV treatment.
      Additionally, the complexation of metals with organic ligands (analyzed by
      comparing metal/DOCSPE and metal/DOSSPE ratios) decreased in the order Cu > As >
      Ni > Cr > Co and thus followed the Irving-Williams order. Differences in riverine
      and marine trace metal containing DOMSPE are summarized by their average molar
      ratios of (C107N4P0.013S1)1000V0.05Cr0.33Co0.19Ni0.39Cu3.41As0.47 in the riverine
      endmember and (C163N7P0.055S1)1000V0.05Cr0.47Co0.16Ni0.07Cu4.05As0.58 in the
      marine endmember.

PMID- 30183725
TI  - Stakeholder opinions on scientific forest management policy implementation in
      Nepal.
AB  - Despite its widespread recognition as a successful model of participatory forest
      management, the community forestry program in Nepal is often criticized for its
      protection-oriented emphasis. Recognizing the need for more active timber
      management, the government of Nepal recently adopted a scientific forest
      management (SFM) policy in the lowland tropical region. In this study, strength,
      weakness, opportunity, and threat analytical hierarchical process criteria were
      employed to understand stakeholder perceptions concerning SFM implementation in
      Nepal. The overall perception was prioritized in the order of strengths (35%),
      threats (28%), opportunities (22%), and weaknesses (16%). The study results
      suggest that there is agreement among stakeholders regarding the need for active
      management of forests in the tropical lowland region. However, the perceptions of
      academic researchers and non-government organization professionals differed from
      those of the other stakeholders in that those two groups were more concerned
      about potential corruption and uncertainties surrounding policy and legal issues.
      The findings suggest that the long-term success of SFM may depend on the ability
      of the government to develop a mechanism that is transparent and capable of
      ensuring equitable benefit sharing among stakeholders. While the stakeholder
      perception analysis performed in this study was focused on SFM implementation in
      Nepal, the results could have implications for other countries that practice the
      participatory model of forest governance as well.

PMID- 30183727
TI  - But they move! Vicariance and dispersal in southern South America: Using two
      methods to reconstruct the biogeography of a clade of lizards endemic to South
      America.
AB  - This study aims to identify events that modeled the historical biogeography of
      Phymaturus, using three methodologies: Spatial Analysis of Vicariance (VIP),
      Statistical Dispersal-Vicariance Analysis (S-DIVA), and Bayesian Binary Method
      MCMC (BBM). In order to assign areas for the Dispersal-Vicariance and the BBM
      analyses, we preferred not to use predefined areas, but to identify areas defined
      via an endemism analysis of Phymaturus species. The analyses were conducted using
      the same basic topology, which we obtained by constructing a metatree with two
      recent phylogenies, both morphology and molecular-based. This topology was also
      used to obtain time divergence estimates in BEAST, using more outgroups than for
      the metatree in order to get more accurate estimates. The S-DIVA analysis based
      on the metatree found 25 vicariance events, 20 dispersals and two extinctions;
      the S-DIVA analysis based on the BEAST tree yielded 30 vicariance events, 42
      dispersal events and five extinctions, and the BBM analysis yielded 63 dispersal
      events, 28 vicariance events and 1 extinction event. According to the metatree
      analysis, the ancestral area for Phymaturus covers northern Payunia and southern
      Central Monte. A vicariant event fragmented the ancestral distribution of the
      genus, resulting in northern Payunia and southern Central Monte as ancestral area
      for the P. palluma group, and southern Payunia for the P. patagonicus group. The
      analysis based on the BEAST tree showed a more complex reconstruction, with
      several dispersal and extinction events in the ancestral node. The Spatial
      Analysis of Vicariance identified 41 disjunct sister nodes and removed 10 nodes.
      The barrier that separates the P. palluma group from the P. patagonicus group is
      roughly congruent with the southern limit of the P. palluma group. The ancestral
      range for the genus occupies a central position relative to the distribution of
      the group, which implies that the species must have migrated to the north (P.
      palluma group) and to the south (P. patagonicus group). To answer questions
      related to the specific timing of the events, a molecular clock for Phymaturus
      was obtained, using a Liolaemus fossil for calibration. The present contribution
      provides a hypothetical framework for the events that modeled the distribution of
      Phymaturus.

PMID- 30183726
TI  - Transcriptome analysis of immune genes in peripheral blood mononuclear cells of
      young foals and adult horses.
AB  - During the neonatal period, the ability to generate immune effector and memory
      responses to vaccines or pathogens is often questioned. This study was undertaken
      to obtain a global view of the natural differences in the expression of immune
      genes early in life. Our hypothesis was that transcriptome analyses of peripheral
      blood mononuclear cells (PBMCs) of foals (on day 1 and day 42 after birth) and
      adult horses would show differential gene expression profiles that characterize
      natural immune processes. Gene ontology enrichment analysis provided assessment
      of biological processes affected by age, and a list of 897 genes with >=2 fold
      higher (p<0.01) expression in day 42 when compared to day 1 foal samples. Up
      regulated genes included B cell and T cell receptor diversity genes; DNA
      replication enzymes; natural killer cell receptors; granzyme B and perforin;
      complement receptors; immunomodulatory receptors; cell adhesion molecules; and
      cytokines/chemokines and their receptors. The list of 1,383 genes that had higher
      (p<0.01) expression on day 1 when compared to day 42 foal samples was populated
      by genes with roles in innate immunity such as antimicrobial proteins; pathogen
      recognition receptors; cytokines/chemokines and their receptors; cell adhesion
      molecules; co-stimulatory molecules; and T cell receptor delta chain. Within the
      742 genes with increased expression between day 42 foal and adult samples, B cell
      immunity was the main biological process (p = 2.4E-04). Novel data on markedly
      low (p<0.0001) TLR3 gene expression, and high (p<=0.01) expression of IL27,
      IL13RA1, IREM-1, SIRL-1, and SIRPalpha on day 1 compared to day 42 foal samples
      point out potential mechanisms of increased susceptibility to pathogens in early
      life. The results portray a progression from innate immune gene expression
      predominance early in life to adaptive immune gene expression increasing with age
      with a putative overlay of immune suppressing genes in the neonatal phase. These
      results provide insight to the unique attributes of the equine neonatal and young
      immune system, and offer many avenues of future investigation.

PMID- 30183728
TI  - Exploring immuno-regulatory mechanisms in the tumor microenvironment: Model and
      design of protocols for cancer remission.
AB  - The tumor microenvironment comprising of the immune cells and cytokines acts as
      the 'soil' that nourishes a developing tumor. Lack of a comprehensive study of
      the interactions of this tumor microenvironment with the heterogeneous sub
      population of tumor cells that arise from the differentiation of Cancer Stem
      Cells (CSC), i.e. the 'seed', has limited our understanding of the development of
      drug resistance and treatment failures in Cancer. Based on this seed and soil
      hypothesis, for the very first time, we have captured the concept of CSC
      differentiation and tumor-immune interaction into a generic model that has been
      validated with known experimental data. Using this model we report that as the
      CSC differentiation shifts from symmetric to asymmetric pattern, resistant cancer
      cells start accumulating in the tumor that makes it refractory to therapeutic
      interventions. Model analyses unveiled the presence of feedback loops that
      establish the dual role of M2 macrophages in regulating tumor proliferation. The
      study further revealed oscillations in the tumor sub-populations in the presence
      of TH1 derived IFN-gamma that eliminates CSC; and the role of IL10 feedback in
      the regulation of TH1/TH2 ratio. These analyses expose important observations
      that are indicative of Cancer prognosis. Further, the model has been used for
      testing known treatment protocols to explore the reasons of failure of
      conventional treatment strategies and propose an improvised protocol that shows
      promising results in suppressing the proliferation of all the cellular sub
      populations of the tumor and restoring a healthy TH1/TH2 ratio that assures
      better Cancer remission.

PMID- 30183729
TI  - DNA barcoding of Malaysian commercial snapper reveals an unrecognized species of
      the yellow-lined Lutjanus (Pisces:Lutjanidae).
AB  - Management of wild fisheries resources requires accurate knowledge on which
      species are being routinely exploited, but it can be hard to identify fishes to
      species level, especially in speciose fish groups where colour patterns vary with
      age. Snappers of the genus Lutjanus represent one such group, where fishes can be
      hard to identify and as a result fisheries statistics fail to capture species
      level taxonomic information. This study employs traditional morphological and DNA
      barcoding approaches to identify adult and juvenile Lutjanus species harvested in
      Malaysian waters. Our results reveal a suite of species that differs markedly
      from those that have previously been considered important in the Malaysian wild
      capture fishery and show that official fisheries statistics do not relate to
      exploitation at the species level. Furthermore, DNA barcoding uncovered two
      divergent groups of bigeye snapper ('Lutjanus lutjanus') distributed on either
      side of the Malay Peninsula, displaying a biogeographical pattern similar to
      distributions observed for many co-occurring reef-distributed fish groups. One of
      these bigeye snapper groups almost certainly represents an unrecognized species
      in need of taxonomic description. The study demonstrates the utility of DNA
      barcoding in uncovering overlooked diversity and for assessing species catch
      composition in a complicated but economically important taxonomic group.

PMID- 30183730
TI  - Distributed transmission power control for communication congestion control and
      awareness enhancement in VANETs.
AB  - The vehicular ad hoc network (VANET) has been identified as one of the most
      promising technologies for managing future intelligent transportation systems.
      This paper proposes a distributed transmission power adjustment algorithm for
      communication congestion control and awareness enhancement to address
      communication congestion problems that can arise in VANETs. The objective of the
      proposed algorithm is to provide maximum awareness of surrounding vehicles'
      status while maintaining a communications channel load below the allowed
      threshold. The proposed algorithm accomplishes this by adjusting the transmission
      range of each vehicle in the network progressively and gradually, while
      monitoring the communications channel load of each vehicle. By changing the
      transmission range of a vehicle little by little according to the communications
      channel load of its neighboring vehicles, the algorithm finds the optimal
      transmission range that provides maximum awareness without resulting in
      communications congestion. In addition, the proposed algorithm appropriately
      controls the channel load in a fair manner without sacrificing awareness of
      specific vehicles in the congested situation. This allows nearby vehicles to
      obtain more peripheral information to help them stay away from potential hazards
      and maintain safety. The proposed algorithm was implemented in a simulation
      environment, and its performance was validated in various traffic scenarios. The
      simulation results show that the proposed algorithm can deal with communication
      congestion by controlling the transmission power fairly to a target threshold in
      various traffic situations.

PMID- 30183731
TI  - Mind over matter. The impact of subjective social status on health outcomes and
      health behaviors.
AB  - Recent insights have shown subjective status to impact health and health
      behavior. It is however unclear how this exactly happens. In this study we
      explore two mechanisms: this of a direct, mediating effect of subjective status
      explaining the impact of material class on health outcomes and behavior and an
      indirect, moderating impact on the relationship between material class and health
      outcomes and behavior. To test this empirically we conduct two studies, focusing
      on Great-Britain, using survey-data from the English Longitudinal Study of Ageing
      (N: 2709-3448) and the Whitehall II-study (N: 6275-6467). Our linear and logistic
      regression analyses show subjective status has a mainly direct impact on health
      outcomes and has both a direct, mediating and indirect, moderating impact on
      health behavior. In the conclusion of our article we reflect on the theoretical
      reasons why subjective status has a direct impact in certain cases, while playing
      an indirect role in other cases.

PMID- 30183732
TI  - Tuberculosis in post-contact Native Americans of Brazil: Paleopathological and
      paleogenetic evidence from the Tenetehara-Guajajara.
AB  - Tuberculosis (TB) has been described in Native American populations prior to the
      arrival of European explorers, and in Brazilian populations dating from the
      Colonial Period. There are no studies demonstrating TB infection in native
      Brazilians, and the history and epidemiological scenario of TB in Brazil is still
      unknown. The aim of this study was to verify the presence of TB infection among
      the native Tenetehara-Guajajara population from Maranhao State, Brazil, 210 +/-
      40 years ago. A Tenetehara-Guajajara skeleton collection was submitted to
      paleopathological analysis, and rib bone samples (n = 17) were used for
      paleogenetic analysis based on Mycobacterium tuberculosis complex (MTC) targets.
      Porotic hyperostosis and cribra orbitalia were found in 10 and 13 individuals,
      respectively. Maternal ancestry analysis revealed Native American mtDNA
      haplogroups A and C1 in three individuals. Three samples showed osteological
      evidence suggestive of TB. katG and mtp40 sequences were detected in three
      individuals, indicating probable TB infection by two MTC lineages. Tuberculosis
      infection in the Tenetehara-Guajajara population since the 18th century points to
      a panorama of the disease resulting, most probably, from European contact.
      However, the important contribution of African slaves in the population of
      Maranhao State, could be also considered as a source of the disease. This study
      provides new data on TB during the Brazilian Colonial Period. This is the first
      report integrating paleopathological and paleogenetic data for the study of TB in
      Brazil.

PMID- 30183733
TI  - Climatic niche and potential distribution of Tithonia diversifolia (Hemsl.) A.
      Gray in Africa.
AB  - Mexican sunflower, Tithonia diversifolia (Asteraceae), is an invasive tropical
      plant species native to Central America. It has spread in more than 70 countries
      across Asia, Africa and Australia. In Africa, this species is known to disturb
      native crops and plant communities, but its negative impacts remain
      underestimated. Moreover, its potential invasion risk has not been investigated
      so far. A fundamental aspect in the identification and prediction of habitats
      susceptible to biological invasions lies in the ability of an organism to
      conserve or change its ecological niche as part of the invasion process. Here, we
      compared the realised climatic niche of T. diversifolia between its Central
      American and African ranges. In addition, reciprocal distribution models were
      calibrated on its native and invaded ranges. Models were combined and projected
      to current and future climatic conditions in Africa to estimate the potential
      distribution of this species. Niche overlap given by Schoner's D index was low
      (0.23), equivalency and similarity tests suggested that the climatic niche of T.
      diversifolia is not similar in both ranges. However the low expansion (U = 0.09)
      and very high stability (S = 0.92) indices support climatic niche conservatism
      for this species in Africa, although it has not filled its entire niche so far.
      Our combined reciprocal models highlight highly suitable areas for this species
      in humid regions throughout East, Central and West Africa, then in some parts of
      South Africa and Madagascar. Future projections indicated that the distribution
      of climatically suitable habitats will likely remain stable.

PMID- 30183734
TI  - Time spent at blood pressure target and the risk of death and cardiovascular
      diseases.
AB  - BACKGROUND: The time a patient spends with blood pressure at target level is an
      intuitive measure of successful BP management, but population studies on its
      effectiveness are as yet unavailable. METHOD: We identified a population-based
      cohort of 169,082 individuals with newly identified high blood pressure who were
      free of cardiovascular disease from January 1997 to March 2010. We used 1.64
      million clinical blood pressure readings to calculate the TIme at TaRgEt (TITRE)
      based on current target blood pressure levels. RESULT: The median (Inter-quartile
      range) TITRE among all patients was 2.8 (0.3, 5.6) months per year, only 1077
      (0.6%) patients had a TITRE >=11 months. Compared to people with a 0% TITRE,
      patients with a TITRE of 3-5.9 months, and 6-8.9 months had 75% and 78% lower
      odds of the composite of cardiovascular death, myocardial infarction and stroke
      (adjusted odds ratios, 0.25 (95% confidence interval: 0.21, 0.31) and 0.22 (0.17,
      0.27), respectively). These associations were consistent for heart failure and
      any cardiovascular disease and death (comparing a 3-5.9 month to 0% TITRE, 63%
      and 60% lower in odds, respectively), among people who did or did not have blood
      pressure 'controlled' on a single occasion during the first year of follow-up,
      and across groups defined by number of follow-up BP measure categories.
      CONCLUSION: Based on the current frequency of measurement of blood pressure this
      study suggests that few newly hypertensive patients sustained a complete, year
      round on target blood pressure over time. The inverse associations between a
      higher TITRE and lower risk of incident cardiovascular diseases were independent
      of widely-used blood pressure 'control' indicators. Randomized trials are
      required to evaluate interventions to increase a person's time spent at blood
      pressure target.

PMID- 30183735
TI  - Fatty acid specific delta13C values reveal earliest Mediterranean cheese
      production 7,200 years ago.
AB  - The earliest evidence for cheese production in the Mediterranean is revealed by
      stable carbon isotope analyses of individual fatty acids in pottery residues from
      the Dalmatian coast of Croatia. Lipid residue data indicate the presence of milk
      in the earliest pottery, Impressed Ware, by 5700 cal. BCE (7700 BP). In contrast,
      by 5200 cal BCE (7200 BP), milk was common in refined Figulina pottery, meat was
      mostly associated with Danilo ware, cheese occurred in Rhyta, and sieves
      contained fermented dairy, representing strong links between specific function
      and stylistically distinctive pottery vessels. Genetic data indicate the
      prevalence of lactose intolerance among early farming populations. However, young
      children are lactase persistent until after weaning and could consume milk as a
      relatively pathogen-free and nutrient rich food source, enhancing their chances
      of survival into adulthood. Fermentation of milk into yogurt and cheese decreases
      lactose content. The evidence for fermented dairy products by 5200 cal BCE
      indicates a larger proportion of the population was able to consume dairy
      products and benefit from their significant nutritional advantages. We suggest
      that milk and cheese production among Europe's early farmers reduced infant
      mortality and helped stimulate demographic shifts that propelled farming
      communities to expand to northern latitudes.

PMID- 30183736
TI  - The green rice leafhopper, Nephotettix cincticeps (Hemiptera: Cicadellidae),
      salivary protein NcSP75 is a key effector for successful phloem ingestion.
AB  - Nephotettix cincticeps, a prevalent rice pest, injects gelling and watery saliva
      into plant tissues during the sucking process. Certain components within the
      saliva are believed to interact with plant cellular constituents and play
      important roles in overcoming host plant defense responses. Based on our previous
      analysis of the salivary gland transcriptome and secreted saliva proteome of N.
      cincticeps, in this study, we analyzed the biological functions of salivary
      protein, NcSP75 (N. cincticeps salivary protein 75 kD). NcSP75, a salivary glands
      specific gene, showed low similarities to any previously reported sequences.
      Knockdown of NcSP75 by RNA interference (RNAi) reduced the longevity of treated
      nymphs to approximately half of the longevity of controls and caused severe
      developmental retardation. Furthermore, the knockdown of NcSP75 decreased the
      survival rate of adults, and reduced the number of deposited eggs and hatched
      nymphs. Thus, the adverse effects caused by the knockdown of NcSP75 were observed
      throughout the lifetime of N. cincticeps, when feeding on rice plants. In
      contrast, no reduction was observed in the survival rate of the knockdown of
      NcSP75 adults fed on an artificial diet. Electrical penetration graph
      measurements taken from adult females feeding on rice plants showed a
      significantly shorter duration of phloem ingestion associated with the knockdown
      of NcSP75 than the knockdown of the enhanced green fluorescent protein (EGFP).
      Furthermore, the total sugar content of the honeydew was lower when NcSP75 was
      knocked down. These results suggest that the NcSP75 protein contribute to
      successful and sustainable ingestion from the sieve elements of rice plants. The
      NcSP75 protein of N. cincticeps can, accordingly, be considered as a key effector
      for establishing compatible interaction with rice plants and could be a potential
      target for controlling this species.

PMID- 30183737
TI  - Physiological analysis of the effect of altitudinal gradients on Leymus secalinus
      on the Qinghai-Tibetan Plateau.
AB  - On the Qinghai-Tibetan Plateau, the high-altitudinal gradients can negatively
      affect plant distribution and limit plant growth and reproduction. Leymus
      secalinus (Georgi) Tzvel. is an important forage crop on the Qinghai-Tibetan
      Plateau and has an excellent ability to fix sand and improve soil. To evaluate
      the effect of altitude on the physiological characteristics of L. secalinus on
      the Qinghai-Tibetan Plateau, we measured the lipid peroxidation; chlorophyll a
      (Chl a), chlorophyll b (Chl b), total carotenoid (Car), soluble protein, proline
      and soluble sugar contents; and the activities of superoxide dismutase (SOD),
      catalase (CAT) and peroxidase (POD) in leaves from eight different altitudes in
      Minhe County and Huangzhong County. The leaves were collected at the initial
      bloom stage, and the average vertical distance between two adjacent collection
      sites was approximately 100 meters. The reduction in Chl a and Chl b contents and
      the increase in Car contents can allow plants to weaken their light absorption
      and avoid photodamage to the chloroplast. The decrease in malondialdehyde (MDA)
      content associated with lower lipid peroxidation, and the changes of CAT, SOD and
      POD activities reflect a higher reactive oxygen species (ROS) scavenging capacity
      in high-altitude plants. The increase in proline and soluble sugar contents with
      elevation suggests that proline and soluble sugar may play a key role in the
      osmotic adjustment of plants in alpine regions. The results suggested that
      altitudinal gradients negatively affect L. secalinus on the Qinghai-Tibetan
      Plateau and that the adaptation mechanism and survival strategies of L. secalinus
      were attributed to the combined effects of multiple protective strategies.

PMID- 30183738
TI  - Biomarkers for classification and class prediction of stress in a murine model of
      chronic subordination stress.
AB  - Selye defined stress as the nonspecific response of the body to any demand and
      thus an inherent element of all diseases. He reported that rats show adrenal
      hypertrophy, thymicolymphatic atrophy, and gastrointestinal ulceration, referred
      to as the stress triad, upon repeated exposure to nocuous agents. However,
      Selye's stress triad as well as its extended version including reduced body
      weight gain, increased plasma glucocorticoid (GC) concentrations, and GC
      resistance of target cells do not represent reliable discriminatory biomarkers
      for chronic stress. To address this, we collected multivariate biological data
      from male mice exposed either to the preclinically validated chronic subordinate
      colony housing (CSC) paradigm or to single-housed control (SHC) condition. We
      then used principal component analysis (PCA), top scoring pairs (tsp) and support
      vector machines (SVM) analyses to identify markers that discriminate between
      chronically stressed and non-stressed mice. PCA segregated stressed and non
      stressed mice, with high loading for some of Selye's stress triad parameters. The
      tsp analysis, a simple and highly interpretable statistical approach, identified
      left adrenal weight and relative thymus weight as the pair with the highest
      discrimination score and prediction accuracy validated by a blinded dataset (92%
      p-value < 0.0001; SVM model = 83% accuracy and p-value < 0.0001). This finding
      clearly shows that simultaneous consideration of these two parameters can be used
      as a reliable biomarker of chronic stress status. Furthermore, our analysis
      highlights that the tsp approach is a very powerful method whose application
      extends beyond what has previously been reported.

PMID- 30183739
TI  - Flipped-classroom training in advanced cardiopulmonary life support.
AB  - BACKGROUND: The effects of the flipped classroom have been demonstrated in
      various fields of education in recent years. Training in emergency medicine is
      also beginning to gradually implement the flipped classroom; however, its
      practical effect in emergency medicine contexts is not yet clear. OBJECTIVE: The
      present study investigates the effects of the flipped classroom on advanced
      cardiopulmonary life support (ACLS) training implemented among practicum students
      in emergency medicine. METHODS: The study randomly assigned into control and
      experimental conditions 108 fourth year students in the College of Medicine at
      Yonsei University, in Seoul, who were scheduled to take clinical practice in
      emergency medicine between March and July 2017. Students were taught about ACLS
      in either a traditional lecture-based classroom (control condition) or a flipped
      classroom (experimental condition); then, simulation training with ACLS scenarios
      was carried out. Finally, each student was rated on performance using a rating
      form developed in advance. RESULTS: ACLS simulation scores of the students in the
      flipped classroom were 70.9+/-10.9, which was higher than those of the students
      in the traditional classroom (67.1+/-11.3); however, this difference was not
      statistically significant (p = 0.339). In addition, the difference in student
      satisfaction as measured on a survey was statistically insignificant (p = 0.655).
      CONCLUSIONS: Competency assessment after simulation-based training in ACLS
      undergone by senior medical students randomly assigned to flipped and traditional
      classrooms showed no statistical difference in competency between the two groups.

PMID- 30183740
TI  - Prolonged fasting-induced metabolic signatures in human skeletal muscle of lean
      and obese men.
AB  - Insulin resistance is a well-known physiological adaptation to prolonged fasting
      in healthy skeletal muscle. Obesity is associated with insulin resistance and
      metabolic inflexibility in skeletal muscle, and a pronounced increase in the risk
      of metabolic complications. Under the hypothesis that the metabolic traits of
      insulin resistance associated with prolonged fasting are different from insulin
      resistance associated with obesity, we examined nine obese and nine lean
      participants during 12 and 72h of fasting, respectively. Insulin resistance in
      obese participants was associated with impaired insulin signaling, and reduced
      levels of glucose-6-phosphate and TCA-cycle intermediates. 72h of fasting in lean
      participants reduced insulin-stimulated glucose uptake to levels similar to obese
      participants fasted for 12h. This was associated with increased lipid oxidation,
      but not accumulation of diacylglycerol or acylcarnitines and impairment of
      insulin signaling. Prolonged fasting was associated with pronounced increases in
      beta-hydroxybutyrate and beta- hydroxybutyrylcarnitine levels in skeletal muscle
      suggesting augmented ketone body metabolism. Fasting induced insulin resistance
      may be a consequence of substrate competition. The underlying mechanism behind
      insulin resistance in obesity is thus not comparable to the physiological
      adaptations in skeletal muscle induced by prolonged fasting in lean participants.

PMID- 30183741
TI  - The immunomodulatory quinoline-3-carboxamide paquinimod reverses established
      fibrosis in a novel mouse model for liver fibrosis.
AB  - Quinoline-3-carboxamides (Q substances) are small molecule compounds with anti
      inflammatory properties. In this study, we used one of these substances,
      Paquinimod, to treat a novel model for chronic liver inflammation and liver
      fibrosis, the NOD-Inflammation Fibrosis (N-IF) mouse. We show that treatment of N
      IF mice significantly reduced inflammation and resulted in the regression of
      fibrosis, even when the treatment was initiated after onset of disease. The
      reduced disease phenotype was associated with a systemic decrease in the number
      and reduced activation of disease-promoting transgenic natural killer T (NKT)-II
      cells and their type 2-cytokine expression profile. Paquinimod treatment also led
      to a reduction of CD115+ Ly6Chi monocytes and CD11b+ F4/80+ CD206+ macrophages.

PMID- 30183742
TI  - Whole-body vibration training in obese subjects: A systematic review.
AB  - OBJECTIVE: (i) to determine the outcomes of whole-body vibration training (WBVT)
      on obese individuals, and the intervention settings producing such effects; (ii)
      identify potential improper or harmful use of WBVT. DESIGN: Systematic review.
      DATA SOURCES: Medline, Scopus, Web of Science, PEDro and Scielo until July 2018.
      ELIGIBILITY CRITERIA: Full papers evaluating the effect of WBVT on body
      composition, cardiovascular status and functional performance in obese adults.
      Papers with PEDro score<4 were excluded. STUDY APPRAISAL AND SYNTHESIS: Risk of
      bias and quality of WBVT reporting were assessed with PEDro scale (randomized
      controlled trials) or TREND checklist (non-randomized studies) and a 14-items
      checklist, respectively. Weighted acceleration, daily exposure and Hedges'
      adjusted g were computed. RESULTS: We included 18 papers published 2010-2017.
      Typical interventions consisted in three sessions/week of exercises (squats, calf
      raises) performed on platforms vibrating at 25-40 Hz (amplitude: 1-2 mm);
      according to ISO 2631-1:1997, daily exposure was "unsafe" in 7/18 studies.
      Interventions lasting >=6 weeks improved cardiac autonomic function and reduced
      central/peripheral arterial stiffness in obese women; 10 weeks of WBVT produced
      significant weight/fat mass reduction, leg strength improvements as resistance
      training, and enhanced glucose regulation when added to hypocaloric diet. No
      paper evidenced losses of lean mass. Isolated cases of adverse effects were
      reported. SUMMARY: To date, WBVT is a promising adjuvant intervention therapy for
      obese women; long-term studies involving larger cohorts and male participants are
      required to demonstrate the associated safety and health benefits. The
      therapeutic use of WBVT in the management of obese patients is still not
      standardised and should be supported by an extensive knowledge on the causality
      between vibration parameters and outcomes.

PMID- 30183743
TI  - No effect of rifaximin on soluble CD163, mannose receptor or type III and IV
      neoepitope collagen markers in decompensated cirrhosis: Results from a
      randomized, placebo controlled trial.
AB  - BACKGROUND AND AIMS: Macrophages play a significant role in chronic liver disease
      as reflected by elevated soluble (s)CD163 and mannose receptor (sMR) levels and
      associated with liver disease severity and prognosis. Extracellular matrix
      remodelling associated with fibrogenesis may be affected by systemic inflammation
      induced by bacterial translocation. Therefore, we aimed to investigate the effect
      of rifaximin-alpha, an antibiotic with effect on gut bacteria, on sCD163, sMR,
      and collagen metabolites. METHODS: Fifty-four clinically stable patients with
      decompensated cirrhosis were randomized to 4 weeks treatment with rifaximin-alpha
      (n = 36) or placebo (n = 18). Macrophage markers sCD163, sMR and markers of
      collagen fibrogenesis (C3M and C4M) and formation (PRO-C3 and P4NPS7) were
      analysed in plasma before and after treatment. RESULTS: sCD163 and sMR levels
      were associated with liver disease severity (MELD score, sCD163 rho = 0.47,
      p<0.001 and sMR rho = 0.37, p = 0.005). There was no effect of Rifaximin-alpha on
      sCD163 levels (median (range) sCD163 5.64(2.02 to 10.8) at baseline versus
      4.42(1.98 to 8.92) at follow-up in the rifaximin-alpha group and 4.85 (2.29 to
      12.1) at baseline versus 4.32 (1.98 to 12.4) at follow-up in the placebo-group),
      p = 0.34); nor sMR levels, p = 0.34. Also in patients with elevated
      lipopolysaccharide binding protein (> 5.9 MUg/ml, 38 patients) there was no
      effect of rifaximin-alpha on sCD163 (p = 0.49) or sMR levels (p = 0.32).
      CONCLUSION: We confirmed that macrophage activation markers sCD163 and sMR are
      directly associated to liver disease severity (MELD score). However, rifaximin
      alpha has no effect on sCD163, sMR or collagen markers in decompensated cirrhosis
      and does therefore not seem to interfere with macrophage activation or
      fibrogenesis.

PMID- 30183744
TI  - Probing behaviors and their plasticity for the aphid Sitobion avenae on three
      alternative host plants.
AB  - Insects may develop different behavioral phenotypes in response to heterogeneous
      environments (e.g., host plants), but the plasticity of their feeding behaviors
      has been rarely explored. In order to address the issue, clones of the English
      grain aphid, Sitobion avenae (Fabricius), were collected from wheat, and their
      probing behaviors were recorded on three plants. Our results demonstrated that S.
      avenae individuals on the alternative plants (i.e., barley and oat) tended to
      have higher frequency of non-probing (Np), increased duration of the pathway
      phase, increased phloem salivation, and decreased phloem ingestion (E2), compared
      to those on the source plant (i.e., wheat), showing the resistance of barley and
      oat to this aphid's feeding. This aphid showed apparently high extents of
      plasticity for all test probing behaviors on barley or oat. Positive selection
      for higher extents of plasticity in E2 duration was identified on barley and oat.
      The factor 'clone' alone explained 30.6% to 70.1% of the total variance for each
      behavioral plasticity, suggesting that the divergence of probing behavior
      plasticity in S. avenae had a genetic basis. This aphid's fitness correlated
      positively with the plasticity of Np frequency and E2 frequency. Some behaviors
      and their corresponding plasticities (e.g., the frequency of xylem ingestion and
      its plasticity) were found to be correlated characters, probably reflecting the
      limits for the evolution of higher extents of behavioral plasticity in this
      aphid. The differential probing behaviors and their plasticity in S. avenae can
      have significant implications for the adaptation and management of aphids on
      different plants.

PMID- 30183745
TI  - Prevention of bacterial colonization on non-thermal atmospheric plasma treated
      surgical sutures for control and prevention of surgical site infections.
AB  - Surgical site infections have a remarkable impact on morbidity, extended
      hospitalization and mortality. Sutures strongly contribute to development of
      surgical site infections as they are considered foreign material in the human
      body. Sutures serve as excellent surfaces for microbial adherence and subsequent
      colonization, biofilm formation and infection on the site of a surgery. Various
      antimicrobial sutures have been developed to prevent suture-mediated surgical
      site infection. However, depending on the site of surgery, antimicrobial sutures
      may remain ineffective, and antimicrobial agents on them might have drawbacks.
      Plasma, defined as the fourth state of matter, composed of ionized gas, reactive
      oxygen and nitrogen species, free radical and neutrals, draws attention for the
      control and prevention of hospital-acquired infections due to its excellent
      antimicrobial activities. In the present study, the efficacy of non-thermal
      atmospheric plasma treatment for prevention of surgical site infections was
      investigated. First, contaminated poly (glycolic-co-lactic acid), polyglycolic
      acid, polydioxanone and poly (glycolic acid-co-caprolactone) sutures were treated
      with non-thermal atmospheric plasma to eradicate contaminating bacteria like
      Staphylococcus aureus and Escherichia coli. Moreover, sutures were pre-treated
      with non-thermal atmospheric plasma and then exposed to S. aureus and E. coli.
      Our results revealed that non-thermal atmospheric plasma treatment effectively
      eradicates contaminating bacteria on sutures, and non-thermal atmospheric plasma
      pre-treatment effectively prevents bacterial colonization on sutures without
      altering their mechanical properties. Chemical characterization of sutures was
      performed with FT-IR and XPS and results showed that non-thermal atmospheric
      plasma treatment substantially increased the hydrophilicity of sutures which
      might be the primary mechanism for the prevention of bacterial colonization. In
      conclusion, plasma-treated sutures could be considered as novel alternative
      materials for the control and prevention of surgical site infections.

PMID- 30183746
TI  - Knowledge, perceptions and confidence of physicians and pharmacists towards
      pharmacogenetics practice in Kuwait.
AB  - BACKGROUND: Pharmacogenetics practice has been successfully implemented in many
      developed countries to enhance personalized medicine and improve clinical and
      economic outcomes. An understanding of healthcare providers' knowledge,
      perceptions, confidence towards pharmacogenetics, and their active enrollment
      with pharmacogenetic testing is essential for test acceptance and utilization.
      This study was designed to assess physicians' and pharmacists' knowledge,
      perceptions, and confidence towards pharmacogenetics, determine the preferred
      learning format for their future education in pharmacogenetics, and identify the
      barriers to its application in their practice settings. METHODS: A cross
      sectional survey was conducted using a pretested self-administered questionnaire
      on a sample of 629 randomly selected physicians and pharmacists. Descriptive and
      comparative analyses were used in data analysis. RESULTS: The response rate was
      98.1%. Less than one-tenth of respondents were exposed to pharmacogenetics
      education or training (8.9%), applied pharmacogenetics testing in their practice
      (9.4%), or provided patient counselling on the results of the pharmacogenetic
      testing (9.1%), and over 90% of them were physicians. The overall respondents'
      mean (SD) total knowledge score percentage was low [45.0% (24)] and there was no
      significant difference between the physicians and pharmacists scores (p>0.05).
      Only 16.0% of participants indicated that they felt confident in applying
      pharmacogenetics in their practice settings. Despite these low levels of
      knowledge and self-confidence, 70.2% of participants expressed overall positive
      perceptions towards pharmacogenetics and its clinical implications. These
      positive overall perceptions were found to be significantly more common among
      pharmacists compared to physicians (p<0.05). The top two perceived barriers
      facing the implementation of pharmacogenetics in Kuwait were lack of education or
      training and clinical guidelines. CONCLUSIONS: These findings highlight important
      concerns and will aid in the assessment of current pharmacogenetics practice.
      Also, they will provide further insight in designing future targeted multifaceted
      interventions to promote the adoption and utilization of pharmacogenetics testing
      in Kuwait.

PMID- 30183747
TI  - Education, poverty and "purity" in the context of adolescent girls' secondary
      school retention and dropout: A qualitative study from Karnataka, southern India.
AB  - BACKGROUND: Gender-related norms and poverty remain important structural barriers
      to secondary school attendance among adolescent girls in southern India. We
      analyse how gender norms interact with family deprivation and dynamics to result
      in girls dropping out of school; we identify the main facilitators of school
      retention and changes to gender socialisation. METHODS: Longitudinal qualitative
      case studies with 36 girls were nested within a cluster randomized trial to
      evaluate the Samata intervention targeting adolescent girls in Bagalkote and
      Vijayapura districts in northern Karnataka. We used two rounds of in-depth
      interviews, conducted in 2014 at a time when respondents were in 8th standard at
      the age of 13 to 14 and sixteen months later. We combined thematic and narrative
      analyses. RESULTS: Our study found that poverty and socioeconomic realities at
      the household level strongly affect conformity with discriminatory gender
      practices such as restricting girls' mobility. The value placed on education by
      parents clearly differentiates the regular school goers from those frequently
      absent and others who dropped out. With active encouragement of the girls'
      educational and career aspirations, parents engendered the girl's agency to
      communicate openly both at home and at school, allowing subtle changes to gender
      performance while resisting the pressure of social sanctions. In contrast, where
      educational aspirations were weak, parents invested more intensely in enforcing
      correct performance of gender, prioritising her well-being by aiming to secure
      her future in a good marriage. Among poorer families, girls' domestic duties came
      at the cost of schooling with concerns about protecting her sexual purity
      predominating. CONCLUSIONS: In contexts where a strong gender ideology of
      virginity before marriage rules, subtle shifts in harmful gender practices are
      possible. Interventions aiming to improve education need to target the most
      deprived families, focussing on trust building through open communication.

PMID- 30183748
TI  - Personality, abnormal behaviour, and health: An evaluation of the welfare of
      police horses.
AB  - An animal's welfare depends on an individual's capacity to adapt to the
      environment in which it lives. This adaptation is directly associated with the
      quality of the environment and to the possibility of expressing natural
      behaviours. Horses kept in stables often display a range of abnormal behaviours
      related to lack of control over their environment, which can lead to behavioural
      and health problems. An individual's personality also plays an important role in
      its susceptibility and resilience to the development of diseases and abnormal
      behaviour; thus, an evaluation of horses' personalities could be crucial to
      selecting individuals best able to cope with different work activities. This
      study aimed to assess the well-being of police horses maintained in a semi
      confinement regime in Brazil by associating their personalities to the occurrence
      of abnormal behaviours and disease. Using a non-invasive approach, different
      tests were performed to investigate the horses' behaviour, personality and
      welfare. A frustration test and a novel object test were conducted with 46 horses
      and the individuals' personalities were assessed using questionnaires and
      behaviour tests. In addition, we evaluated their physical health through a survey
      of their veterinary records. The data for horses were evaluated individually. The
      results demonstrated the occurrence of multiple abnormal behaviours motivated by
      factors such as diet and lack of social contact. Moreover, the personality tests
      indicated this is an important component when evaluating welfare, since
      correlations were found between personality traits and abnormal behaviour
      expression, and between personality traits and health problems. According to our
      results, passive, stubborn, and confident horses are better suited to be selected
      as police horses. The ability to classify horses according to their personalities
      could help in selecting horses most suitable for patrolling, thereby helping to
      reduce behavioural problems and increasing animal well-being.

PMID- 30183749
TI  - Centrifugation-induced release of ATP from red blood cells.
AB  - Centrifugation is the primary preparation step for isolating red blood cells
      (RBCs) from whole blood, including for use in studies focused on transduction of
      adenosine triphosphate (ATP), an important vasodilatory signaling molecule.
      Despite the wide use of centrifugation, little work has focused on how the
      centrifugation itself affects release of ATP from RBCs prior to subsequent
      experimentation. Here we report that both the centrifugation force and duration
      have a pronounced impact on the concentration of ATP present in the packed RBCs
      following centrifugation. Multiple subsequent centrifugations yield extracellular
      ATP concentrations comparable to the amount released during the initial
      centrifugation, suggesting this effect is cumulative. Pairwise measurements of
      hemoglobin and ATP suggest the presence of ATP is primarily due to an increase in
      centrifugation-induced hemolysis. These results indicate that common
      centrifugation parameters, within the ranges explored here, can release ATP in
      quantities comparable to the low end of the range of values measured in typical
      ATP transduction experiments, potentially complicating experimental
      interpretation of those results.

PMID- 30183750
TI  - Characterization of new, efficient Mycobacterium tuberculosis topoisomerase-I
      inhibitors and their interaction with human ABC multidrug transporters.
AB  - Drug resistant tuberculosis (TB) is a major worldwide health problem. In addition
      to the bacterial mechanisms, human drug transporters limiting the cellular
      accumulation and the pharmacological disposition of drugs also influence the
      efficacy of treatment. Mycobacterium tuberculosis topoisomerase-I (MtTopo-I) is a
      promising target for antimicrobial treatment. In our previous work we have
      identified several hit compounds targeting the MtTopo-I by in silico docking.
      Here we expand the scope of the compounds around three scaffolds associated with
      potent MtTopo-I inhibition. In addition to measuring the effect of newly
      generated compounds on MtTopo-I activity, we characterized the compounds'
      antimicrobial activity, toxicity in human cells, and interactions with human
      multidrug transporters. Some of the newly developed MtTopo-I inhibitors have
      strong antimicrobial activity and do not harm mammalian cells. Moreover, our
      studies revealed significant human ABC drug transporter interactions for several
      MtTopo-I compounds that may modify their ADME-Tox parameters and cellular
      effects. Promising new drug candidates may be selected based on these studies for
      further anti-TB drug development.

PMID- 30183752
TI  - Generation and selection of pluripotent stem cells for robust differentiation to
      insulin-secreting cells capable of reversing diabetes in rodents.
AB  - Induced pluripotent stem cell (iPSC) technology enables the creation and
      selection of pluripotent cells with specific genetic traits. This report
      describes a pluripotent cell line created specifically to form replacement
      pancreatic cells as a therapy for insulin-dependent diabetes. Beginning with
      primary pancreatic tissue acquired through organ donation, cells were isolated,
      re-programmed using non-integrating vectors and exposed to a four day
      differentiation protocol to generate definitive endoderm, a developmental
      precursor to pancreas. The best performing iPSC lines were then subjected to a 12
      day basic differentiation protocol to generate endocrine pancreas precursors. The
      line that most consistently generated highly pure populations was selected for
      further development. This approach created an iPSC-variant cell line, SR1423,
      with a genetic profile correlated with preferential differentiation toward
      endodermal lineage at the loss of mesodermal potential. This report further
      describes an improved differentiation protocol that, coupled with SR1423,
      generated populations of greater than 60% insulin-expressing cells that secrete
      insulin in response to glucose and are capable of reversing diabetes in rodents.
      Created and banked following cGMP guidelines, SR1423 is a candidate cell line for
      the production of insulin-producing cells useful for the treatment of diabetes.

PMID- 30183751
TI  - Identification and comparison of key RNA interference machinery from western corn
      rootworm, fall armyworm, and southern green stink bug.
AB  - RNA interference (RNAi)-based technology shows great potential for use in
      agriculture, particularly for management of costly insect pests. In the decade
      since the insecticidal effects of environmentally-introduced RNA were first
      reported, this treatment has been applied to several types of insect pests.
      Through the course of those efforts, it has become apparent that different
      insects exhibit a range of sensitivity to environmentally-introduced RNAs. The
      variation in responses across insect is not well-understood, with differences in
      the underlying RNAi mechanisms being one explanation. This study evaluates eight
      proteins among three agricultural pests whose responses to environmental RNAi are
      known to differ: western corn rootworm (Diabrotica virgifera virgifera), fall
      armyworm (Spodoptera frugiperda), and southern green stink bug (Nezara viridula).
      These proteins have been identified in various organisms as centrally involved in
      facilitating the microRNA- and small interfering-RNA-mediated interference
      responses. Various bioinformatics tools, as well as gene expression profiling,
      were used to identify and evaluate putative homologues for characteristics that
      may contribute to the differing responses of these insects, such as the absence
      of critical functional domains within expressed sequences, the absence of entire
      gene sequences, or unusually low or undetectable expression of critical genes.
      Though many similarities were observed, the number of isoforms and expression
      levels of double-stranded RNA-binding and argonaute proteins varied across
      insect. Differences among key RNAi machinery genes of these three pests may
      impact the function of their RNAi pathways, and therefore, their respective
      responses to exogenous RNAs.

PMID- 30183753
TI  - Dosimetric superiority of IMRT with jaw tracking technique for whole esophagus
      and T-shaped field radiotherapy in advanced esophageal cancer.
AB  - PURPOSE: For whole esophagus and T-shaped field radiotherapy using intensity
      modulated radiotherapy (IMRT) technique in advanced esophageal cancer, lower
      absorbed doses to lung and heart remains a challenge. The aim of this study was
      to investigate the dosimetric superiority in IMRT plans with jaw tracking
      technique for whole esophagus radiotherapy. METHODS AND MATERIALS: Thirty-two
      patients with esophageal cancer were subjected to IMRT treatment plans using
      Eclipse treatment planning system. For every patient, four different plans were
      generated with six gantry angles: six large fields IMRT plans with fixed jaw (6F
      IMRT), six large fields IMRT plans with jaw tracking technique (6F-IMRT-T),
      twelve small fields IMRT plans with fixed jaw (12F-IMRT), and twelve small fields
      IMRT plans with jaw tracking technique (12F-IMRT-T). Dosimetric evaluation was
      assessed for all plans. RESULTS: For every technique, there were no differences
      in planning target volume (PTV) coverage and conformity. 6F-IMRT-T plans could
      significantly reduce lung irradiation with 7.9% (P<0.001) reduction in V5lung and
      2.5% (P<0.001) reduction in V20 lung respectively compared to 6F-IMRT plans. 12F
      IMRT-T plans resulted in superior plans compared to 12-IMRT plans with a
      reduction of 2.9% (P<0.001) in V5lung and 0.9% (P<0.001) in V20 lung,
      respectively. For heart irradiation, 6F-IMRT-T and 12F-IMRT-T plans were slightly
      superior to 6F-IMRT and 12-IMRT plans respectively with a reduction of 1.1 Gy and
      0.5 Gy in the respective mean doses. CONCLUSIONS: By the use of jaw tracking
      technique, the IMRT plans resulted in further lung and heart sparing compared to
      fixed jaw plans for radiotherapy in esophageal cancer.

PMID- 30183754
TI  - Fluorinated methacrylamide chitosan hydrogel dressings enhance healing in an
      acute porcine wound model.
AB  - Wound healing involves multiple interrelated processes required to lead to
      successful healing outcomes. Phagocytosis, inflammation, cell proliferation,
      angiogenesis, energy production, and collagen synthesis are all directly or
      indirectly dependent on oxygen. Along with other critical factors, such as
      nutrition and comorbidities, availability of oxygen is a key determinant of
      healing success. Previously, we have presented a novel oxygenated hydrogel
      material that can be made into dressings for continuous localized oxygen delivery
      to wounds. In this study, an acute porcine wound model was used to test the
      healing benefits of these oxygenated MACF (MACF + O2) hydrogel dressings compared
      to controls, which included commercial Derma-GelTM hydrogel dressings. Wound
      closure and histological analyses were performed to assess re-epithelialization,
      collagen synthesis, angiogenesis, and keratinocyte maturation. Results from these
      assays revealed that wounds treated with MACF + O2 hydrogel dressings closed
      faster as compared to Derma-Gel (p<0.05). Targeted metabolomics via liquid
      chromatography separation and mass spectrometric detection (LC-MS/MS) and a
      biochemical assay determined the concentration of hydroxyproline in wound samples
      at days 14 and 21, showing that MACF + O2 hydrogel dressings improved wound
      healing via an upregulated collagen synthesis pathway as compared to Derma-Gel
      (p<0.05). Histological evidence showed that MACF + O2 hydrogel dressings improve
      new blood vessel formation and keratinocyte maturation over all other treatments.

PMID- 30183755
TI  - The use of anticoagulants in patients with non-valvular atrial fibrillation
      between 2005 and 2014: A drug utilization study using claims data in Japan.
AB  - BACKGROUND: Anticoagulant therapy is recommended in patients with atrial
      fibrillation (AF) but remains underused. The proper use of anticoagulants has
      been encouraged in guidelines frequently published over the past two decades.
      MATERIALS AND METHODS: In this study, we used insurance claims data collected
      from 2005 to 2014 to investigate the prevalence and incidence of non-valvular AF
      (NVAF) patients aged 20 to 74 years standardized to the Japanese population in
      2012 and subdivided by stroke prevention drug type. We estimated the frequency of
      coagulation monitoring in patients with incident NVAF undergoing warfarin therapy
      in 2011 and later. RESULTS: From 2005 to 2014, the standardized prevalence of
      NVAF increased from 117/100,000 to 278/100,000 and the proportion of
      anticoagulant users increased from 38.4% to 58.0%, while that of antiplatelet
      monotherapy decreased from 32.3% to 12.0%. The standardized incidence of NVAF was
      stable at ~40/100,000 patient-years. The proportion of those patients who started
      anticoagulant soon after the initial diagnosis increased from 19.9% to 49.1% from
      2006 to 2013. Among patients who started warfarin, switchers to DOAC had more
      frequent coagulation monitoring than non-switchers. CONCLUSION: The use of
      anticoagulant therapy has gradually increased in patients with NVAF in Japan
      during the study period from 2005 to 2014.

PMID- 30183756
TI  - Prognostic importance and determinants of uremic pruritus in patients receiving
      peritoneal dialysis: A prospective cohort study.
AB  - BACKGROUND: Uremic pruritus is a common and frustrating symptom among patients
      receiving peritoneal dialysis (PD). This study aimed to examine the prognostic
      importance of uremic pruritus and to identify the determinants for higher
      pruritus intensity in PD patients. METHODS: We conducted a prospective cohort
      study of patients receiving maintenance PD. A visual analogue scale (VAS) score
      was used to measure the intensity of uremic pruritus. The composite endpoint of
      PD technique failure or all-cause death was assessed using a multivariable Cox
      proportional hazards model. The determinants for the VAS score of uremic pruritus
      was assessed using a multivariable linear regression model. RESULTS: Among the 85
      PD patients, 24 (28%) had uremic pruritus. During a median follow-up of 28.0
      months, 12 patients experienced technique failure, and 7 died. We found that a
      higher VAS score of pruritus intensity was an independent risk factor for
      technique failure or death (hazard ratio, 1.64; 95% confidence interval, 1.18 to
      2.28; P = 0.003) after adjusting for a variety of confounding factors. We also
      found that a weekly total Kt/V of less than 1.88, a longer duration of dialysis,
      a higher dietary protein intake, and higher blood levels of intact parathyroid
      hormone and high-sensitivity C-reactive protein were independent determinants of
      higher VAS scores of pruritus intensity. CONCLUSIONS: Our results show that
      uremic pruritus is an independent risk factor of technique failure and death in
      patients receiving PD. We also found that a weekly total Kt/V < 1.88 is
      associated with higher intensity of uremic pruritus in PD patients.

PMID- 30183758
TI  - Trends in Hispanic and non-Hispanic white cesarean delivery rates on the US
      Mexico border, 2000-2015.
AB  - BACKGROUND: Cesarean delivery occurs in one in three US births and poses risks
      for mothers and infants. Hispanic cesarean rates were higher than non-Hispanic
      white rates in the US in 2016. In 2009, cesarean rates among Hispanics on the US
      Mexico border exceeded rates among US Hispanics. Since 2009, rates have declined
      nationwide, but border Hispanic rates have not been studied. OBJECTIVE: To
      compare cesarean delivery rates and trends in Hispanics and non-Hispanic whites
      in border and nonborder counties of the four US border states before and after
      2009. STUDY DESIGN: We used data from birth certificates to calculate percentages
      of cesarean deliveries among all births and births to low-risk nulliparous women
      during 2000-2015, and among births to low-risk women with and without a previous
      cesarean during 2009-2015. We calculated 95% confidence intervals around rates
      and used regular and piecewise linear regression to estimate trends for four
      ethnic-geographic subpopulations defined by combinations of Hispanic ethnicity
      and border-nonborder status. RESULTS: Of the four subpopulations, border Hispanic
      rates were highest every year for all cesarean outcomes. In 2015 they were 38.3%
      overall, 31.4% among low-risk nulliparous women, and 21.1% and 94.6% among low
      risk women without and with a previous cesarean, respectively. Nonborder Hispanic
      rates in 2015 were lowest for all outcomes but repeat cesarean. Rates for all
      four subpopulations rose steadily during 2000-2009. Unlike rates for non-Hispanic
      whites, border and nonborder Hispanic rates did not decline post-2009. Most of
      the border Hispanic excess can be attributed to higher cesarean rates in Texas.
      DISCUSSION: Border Hispanic cesarean rates remain higher than those among other
      Hispanics and non-Hispanic whites in border states and show no signs of
      declining. This continuing disparity warrants further analysis using individual
      as well as hospital, environmental and other contextual factors to help target
      prevention measures.

PMID- 30183757
TI  - Identifying genetic diversity of O antigens in Aeromonas hydrophila for molecular
      serotype detection.
AB  - Aeromonas hydrophila is a globally occurring, potentially virulent, gram-negative
      opportunistic pathogen that is known to cause water and food-borne diseases
      around the world. In this study, we use whole genome sequencing and in silico
      analyses to identify 14 putative O antigen gene clusters (OGCs) located
      downstream of the housekeeping genes acrB and/or oprM. We have also identified 7
      novel OGCs by analyzing 15 publicly available genomes of different A. hydrophila
      strains. From the 14 OGCs identified initially, we have deduced that O antigen
      processing genes involved in the wzx/wzy pathway and the ABC transporter
      (wzm/wzt) pathway exhibit high molecular diversity among different A. hydrophila
      strains. Using these genes, we have developed a multiplexed Luminex-based array
      system that can identify up to 14 A. hydrophila strains. By combining our other
      results and including the sequences of processing genes from 13 other OGCs (7
      OGCs identified from publicly available genome sequences and 6 OGCs that were
      previously published), we also have the data to create an array system that can
      identify 25 different A. hydrophila serotypes. Although clinical detection,
      epidemiological surveillance, and tracing of pathogenic bacteria are typically
      done using serotyping methods that rely on identifying bacterial surface O
      antigens through agglutination reactions with antisera, molecular methods such as
      the one we have developed may be quicker and more cost effective. Our assay shows
      high specificity, reproducibility, and sensitivity, being able to classify A.
      hydrophila strains using just 0.1 ng of genomic DNA. In conclusion, our findings
      indicate that a molecular serotyping system for A. hydrophila could be developed
      based on specific genes, providing an important molecular tool for the
      identification of A. hydrophila serotypes.

PMID- 30183759
TI  - Quantifying the effects of pollen nutrition on honey bee queen egg laying with a
      new laboratory system.
AB  - Honey bee populations have been declining precipitously over the past decade, and
      multiple causative factors have been identified. Recent research indicates that
      these frequently co-occurring stressors interact, often in unpredictable ways,
      therefore it has become important to develop robust methods to assess their
      effects both in isolation and in combination. Most such efforts focus on honey
      bee workers, but the state of a colony also depends on the health and
      productivity of its queen. However, it is much more difficult to quantify the
      performance of queens relative to workers in the field, and there are no
      laboratory assays for queen performance. Here, we present a new system to monitor
      honey bee queen egg laying under laboratory conditions and report the results of
      experiments showing the effects of pollen nutrition on egg laying. These findings
      suggest that queen egg laying and worker physiology can be manipulated in this
      system through pollen nutrition, which is consistent with findings from field
      colonies. The results generated using this controlled, laboratory-based system
      suggest that worker physiology controls queen egg laying behavior. Additionally,
      the quantitative data generated in these experiments highlight the utility of the
      system for further use as a risk assessment tool.

PMID- 30183760
TI  - Compression in cultural evolution: Homogeneity and structure in the emergence and
      evolution of a large-scale online collaborative art project.
AB  - Cultural evolutionary theory provides a framework for explaining change in
      population-level distributions. A consistent finding in the literature is that
      multiple transmission episodes shape a distribution of cultural traits to become
      more compressible, i.e., a set of derived traits are more compressed than their
      ancestral forms. Importantly, this amplification of compressible patterns can
      become manifest in two ways, either via the homogenisation of variation or
      through the organisation of variation into structured and specialised patterns.
      Using a novel, large-scale dataset from Reddit Place, an online collaborative art
      project, we investigate the emergence and evolution of compressible patterns on a
      1000x1000 pixel canvas. Here, all Reddit users could select a coloured pixel,
      place it on the canvas, and then wait for a fixed period before placing another
      pixel. By analysing all 16.5 million pixel placements by over 1 million
      individuals, we found that compression follows a quadratic trajectory through
      time. From a non-structured state, where individual artworks exist relatively
      independently from one another, Place gradually transitions to a structured state
      where pixel placements form specialised, interdependent patterns.

PMID- 30183761
TI  - Influence of respiratory mode on the thermal tolerance of intertidal limpets.
AB  - Predicting ecological responses to climate change requires an understanding of
      the mechanisms that influence species' tolerances to temperature. Based on the
      idea that air and water breathing animals are differentially suited to life in
      either medium due to differences in their respiratory morphology, we examined the
      possibility that the thermal tolerances of co-existing intertidal pulmonate and
      patellogastropod limpets may differ in different breathing media. We tested this
      by determining each species' median lethal temperature (LT50) and cardiac
      Arrhenius breakpoint temperature (ABT) as measures of upper thermal tolerance
      limits, in air and water. Although all these species can survive in air and
      water, we hypothesised that the pulmonate limpets, Siphonaria capensis and S.
      serrata, would have higher thermal limits than the patellogastropod limpets,
      Cellana capensis and Scutellastra granularis, in air and vice versa in water. The
      results did not support our hypotheses, since C. capensis had similar thermal
      tolerance limits to the pulmonate limpets in air and the pulmonate limpets had
      thermal tolerance limits similar to or higher than S. granularis in water. Thus,
      considering pulmonate and patellid limpets as groups, we found no differences in
      their collective upper thermal tolerance limits in either medium. We conclude
      that differences between these two limpet groups in their respiratory morphology
      do not influence thermal tolerance, but that tolerances are species-specific.

PMID- 30183762
TI  - Age determination for whitespotted conger Conger myriaster through somatic and
      otolith morphometrics.
AB  - It is difficult to determine ages of eels via otoliths, because multiple
      alternating translucent and opaque zones in the otoliths are hard to identify. In
      this study, we developed an efficient age determination method for whitespotted
      conger (Conger myriaster), using random forest models with otolith weight and
      length, total body length, capture location and season as predictors. 409
      specimens were collected from six locations in Yellow and East China Sea between
      October 2016 and December 2017. Overall OOB error rate was 17.36% compared with
      16.26% for the external cross-validation dataset, and the error of age was within
      one year. Otolith weight and total length were the most important predictors,
      followed by otolith length, capture locations and seasons. There were no
      significant differences between the results derived from otolith/somatic
      morphometrics and otoliths annuli in the estimation of age composition and von
      Betalanffy Growth Functions growth curve. Our results demonstrated that random
      forest model with otolith and somatic morphometrics is an efficient and reliable
      approach for age determination of C. myriaster, which may also be applied to
      other eel species.

PMID- 30183763
TI  - Does implicit motor learning lead to greater automatization of motor skills
      compared to explicit motor learning? A systematic review.
AB  - BACKGROUND: Implicit motor learning is considered to be particularly effective
      for learning sports-related motor skills. It should foster movement automaticity
      and thereby facilitate performance in multitasking and high-pressure
      environments. To scrutinize this hypothesis, we systematically reviewed all
      studies that compared the degree of automatization achieved (as indicated by dual
      task performance) after implicit compared to explicit interventions for sports
      related motor tasks. METHODS: For this systematic review (CRD42016038249)
      conventional (MEDLINE, CENTRAL, Embase, PsycINFO, SportDiscus, Web of Science)
      and grey literature were searched. Two reviewers independently screened reports,
      extracted data, and performed risk of bias assessment. Implicit interventions of
      interest were analogy-, errorless-, dual-task-, and external focus learning. Data
      analysis involved descriptive synthesis of group comparisons on absolute motor
      dual-task (DT) performance, and motor DT performance relative to single-task
      motor performance (motor DTCs). RESULTS: Of the 4125 reports identified, we
      included 25 controlled trials that described 39 implicit-explicit group
      comparisons. Risk of bias was unclear across trials. Most comparisons did not
      show group differences. Some comparisons showed superior absolute motor DT
      performance (N = 2), superior motor DTCs (N = 4), or both (N = 3) for the
      implicit compared to the explicit group. The explicit group showed superior
      absolute motor DT performance in two comparisons. CONCLUSIONS: Most comparisons
      did not show group differences in automaticity. The remaining comparisons leaned
      more toward a greater degree of movement automaticity after implicit learning
      than explicit learning. However, due to an overall unclear risk of bias the
      strength of the evidence is level 3. Motor learning-specific guidelines for
      design and especially reporting are warranted to further strengthen the evidence
      and facilitate low-risk-of-bias trials.

PMID- 30183764
TI  - Effects of schooling on aspects of attention in rural Burkina Faso, West Africa.
AB  - BACKGROUND: We aimed to study the effects of schooling on aspects of attention
      using the Test of Variables of Attention (TOVA) among children in rural Burkina
      Faso. METHODS: We re-enrolled children of a previously community-based cluster
      randomized exclusive breastfeeding trial in rural Burkina Faso. A total of 534
      children (280 boys and 254 girls) aged 6 to 8 years were assessed using the TOVA.
      We examined the effect size difference using Cohen's d, ANOVA and conducted
      regression analyses. RESULTS: Forty nine percent of the children were in school.
      Children not in school performed poorly with a small effect size difference for
      'Response Time', 'Errors of omission', and 'Errors of commission' compared to
      children in school. The effect size difference was moderate for 'Response Time
      Variability', and 'D prime score'. CONCLUSION: Schooling affects different
      aspects of attention in rural Burkina Faso. In settings where literacy and
      schooling rate is low, public sensitizations of the benefits of schooling need to
      be reinforced and advice on sending children to school need to be provided
      continuously.

PMID- 30183765
TI  - Characterization and assessment of HBV chronically infected patients:
      Identification of those eligible for treatment in the South West region of
      Cameroon.
AB  - BACKGROUND: The management of patients with chronic hepatitis B infection is
      quite complex because it requires an in-depth knowledge of the natural history of
      the disease. This study was aimed at characterizing HBV infected patients in
      order to determine the phase of the infection and identify the proportion
      eligible for treatment using 3 different guidelines. METHODS: HBV chronically
      infected patients (negative for HIV and HCV) were enrolled and the following
      tests were done for them: ALT, AST, HBV viral load, HBV serologic panel and Full
      blood count. APRI score was calculated for all patients. These patients were
      classified into immunotolerant, immune clearance, immune control and immune
      escape phases of the infection. The WHO and the 2018 AASLD criteria was also used
      to identify those who need treatment. Patients were clinically examined for signs
      and symptoms. Questionnaire was administered to all participants to ascertain
      their treatment status. Statistical analysis was done using SPSS version 21.
      RESULTS: A total of 283 participants (101 females and 182 males) with a mean age
      of 31.3+/-8.5 were enrolled. Fifty-two (18.4%) were eligible for treatment
      (Immune clearance and immune escape phases) and they recorded a significantly
      higher mean APRI score (0.71+/-0.51) as compared to those in the immune control
      and immune tolerant phase (0.43+/-0.20). Based on WHO and AASLD criteria,
      12(4.2%) and 15 (5.3%) were eligible for treatment respectively and these were
      all subsets of the 52 cases mentioned above. Six (2.1%) and 29 (10.2%) of those
      identified under the immune control phase were on tenofovir and traditional
      medication respectively. CONCLUSION: Considering treatment for patients in the
      immune clearance and immune escape phases of the infection can be a reliable
      strategy to implement in our setting as this may probably tie with considerations
      from other treatment guidelines. Fifty-two (18.4%) patients were eligible for
      treatment and none of them were among the 2.1% of patients put on Tenofovir based
      treatment. This calls for the need for more trained health experts to
      periodically assess patients, implement an adequate treatment guideline and place
      the right patients on treatment in Cameroon.

PMID- 30183766
TI  - Routine data underestimates the incidence of first-line antiretroviral drug
      discontinuations due to adverse drug reactions: Observational study in two South
      African cohorts.
AB  - INTRODUCTION: Estimating the incidence of antiretroviral discontinuations due to
      adverse drug reactions (ADRs) is important to inform antiretroviral treatment
      (ART) regimen recommendations, and to guide prescribing and monitoring policies.
      Routinely collected clinical data is a useful source of pharmacovigilance data.
      We estimated the incidences of first-line antiretroviral discontinuations due to
      ADRs using routine clinical data, and compared them with incidences estimated
      using data enhanced by folder review, in two South African cohorts. METHODS: We
      included patients 16 years and older on first-line ART. We selected a stratified
      random sample of 25% for checking of ART prescription data and reasons for
      antiretroviral discontinuations retrospectively, including folders reviews where
      required (enhanced-data sample). We estimated the incidence of antiretroviral
      discontinuations using Kaplan-Meier and competing risk analyses. RESULTS: In
      15396 patients, 40% had a first-line antiretroviral discontinuation by three
      years on ART. We could determine the reason for 65% of discontinuations using
      routine data only, and 84% of discontinuations, in the enhanced-data sample of
      3837 patients. ADR was the most common reason for discontinuations. In the
      enhanced-data sample, the cumulative incidence of discontinuations due to ADRs by
      three years was 30.4% (95% CI: 24.4-36.6) for stavudine; 2.0% (95% CI: 1.5-2.6)
      for tenofovir, and 1.3% (95% CI: 0.8-2.1) for efavirenz. Using routine data only,
      the cumulative incidences of discontinuations due to ADRs by three years for
      stavudine, tenofovir, and efavirenz respectively were 23.9% (95% CI: 20.3-27.7),
      1.2% (95% CI: 0.9-1.4) and 0.5% (95% CI: 0.3-0.7). CONCLUSIONS: Although the
      relative rankings were similar using routine or enhanced data, lack of checking
      for missing reasons for discontinuation resulted in underestimates of the
      incidence of antiretroviral discontinuations due to ADRs. Systems to improve data
      collection of reasons for regimen changes prospectively would increase the
      capacity of routine data to answer pharmacovigilance questions.

PMID- 30183767
TI  - Pathological prognostic markers in central nervous system solitary fibrous
      tumour/hemangiopericytoma: Evidence from a small series.
AB  - BACKGROUND: Primary central nervous system (CNS) solitary fibrous
      tumour/hemangiopericytoma (SFT/HPC) is a rare neoplasm and its classification
      criteria have been redefined by the latest WHO Classification of CNS Tumours.
      Outcome can vary significantly among patients, thus reliable prognostic markers
      are warranted. METHODS: Primary CNS SFT/HPC diagnosed at the Pathology Unit of
      our Institution between 2006 and 2016 were retrospectively collected. Tumour
      grade along with immunohistochemistry for Ki67, STAT6, PHH3, CD34 and Bcl-2 were
      assessed. TERT promoter status was evaluated by Sanger sequencing. RESULTS:
      Fifteen SFT/HPC were analysed: 9/15 (60%) female, median age at diagnosis 60
      (range: 10-67). Six (40%) cases showed a SFT phenotype and mean H&E-mitotic count
      was 4.8/10 HPF. Tumour grade was I in 6, II in 4 and III in 5 cases. Mean PHH3
      mitotic count was higher than H&E count (8.4 versus 4.8/10 HPF), but it would
      have determined a change in tumour grade in a sole case. Nuclear staining for
      STAT6 was present in 14/15 (93.3%). CD34 and Bcl-2 expression rates were lower in
      higher grade tumours. TERT promoter was mutated in two cases. Median follow up
      time was 2.4 years (6 months-7.4 years) and 5/15 (33%) patients developed local
      disease recurrence. Partial resection (p = 0.0185), higher WHO grade (p = 0.038),
      lower CD34 (p = 0.038) and Bcl-2 (p = 0.010) expressions were significantly
      associated with a poorer disease-free interval. CONCLUSIONS: WHO grade is the
      main prognostic tool in CNS SFT/HPC, but it could be integrated by other markers,
      like CD34 and Bcl-2, in the clinical practice. The relevance of TERT promoter
      mutations in this subset of CNS tumours needs further evaluation.

PMID- 30183768
TI  - Correction: Pathophysiology of Endometriosis: Role of High Mobility Group Box-1
      and Toll-Like Receptor 4 Developing Inflammation in Endometrium.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0148165.].

PMID- 30183769
TI  - The porcine odorant-binding protein as molecular probe for benzene detection.
AB  - In recent years, air pollution has been a subject of great scientific and public
      interests for the strong impact on human health. Air pollution is due to the
      presence in the atmosphere of polluting substances, such as carbon monoxide,
      sulfur and nitrogen oxides, particulates and volatile organic compounds (VOCs),
      derived predominantly from various combustion processes. Benzene is a VOC
      belonging to group-I carcinogens with a toxicity widely demonstrated. The
      emission limit values and the daily exposure time to benzene (TLV-TWA) are
      5MUg/m3 (0.00157 ppm) and 1.6mg/m3 (0.5 ppm), respectively. Currently, expensive
      and time-consuming analytical methods are used for detection of benzene. These
      methods require to perform a few preliminary steps such as sampling, and matrices
      pre-treatments. In addition, it is also needed the support of specialized
      personnel. Recently, single-walled carbon nanotube (SWNTs) gas sensors with a
      limit detection (LOD) of 20 ppm were developed for benzene detection. Other
      innovative bioassay, called bio-report systems, were proposed. They use a whole
      cell (Pseudomona putida or Escherichia coli) as molecular recognition element and
      exhibit a LOD of about 10 MUM. Here, we report on the design of a highly
      sensitive fluorescence assay for monitoring atmospheric level of benzene. For
      this purpose, we used as molecular recognition element the porcine odorant
      binding protein (pOBP). 1-Aminoanthracene was selected as extrinsic fluorescence
      probe for designing a competitive fluorescence resonance energy transfer (FRET)
      assay for benzene detection. The detection limit of our assay was 3.9MUg/m3, a
      value lower than the actual emission limit value of benzene as regulated by
      European law.

PMID- 30183770
TI  - Modulating the antioxidant system by exogenous 2-(3,4-dichlorophenoxy)
      triethylamine in maize seedlings exposed to polyethylene glycol-simulated drought
      stress.
AB  - Maize (Zea mays L.), an important agricultural crop, suffers from drought stress
      frequently during its growth period, thus leading to a decline in yield. 2-(3,4
      Dichlorophenoxy) triethylamine (DCPTA) regulates many aspects of plant
      development; however, its effects on crop stress tolerance are poorly understood.
      We pre-treated maize seedlings by adding DCPTA to a hydroponic solution and then
      subjected the seedlings to a drought condition [15% polyethylene glycol (PEG)
      6000 treatment]. The activities of superoxide dismutase (SOD), peroxidase (POD),
      ascorbate peroxidase (APX), and glutathione reductase (GR) were enhanced under
      drought stress and further enhanced by the DCPTA application. The activities of
      monodehydroascorbate reductase (MDHAR), dehydroascorbate reductase (DHAR) and
      catalase (CAT) declined continuously under drought stress; however, the
      activities partially recovered with DCPTA application. Up-regulation of the
      activities and transcript levels of APX, GR, MDHAR and DHAR in the DCPTA
      treatments contributed to the increases in ascorbate (AsA) and glutathione (GSH)
      levels and inhibited the increased generation rate of superoxide anion radicals
      (O2.-), the contents of hydrogen peroxide (H2O2) and malondialdehyde (MDA), and
      the electrolyte leakage (EL) induced by drought. These results suggest that the
      enhanced antioxidant capacity induced by DCPTA application may represent an
      efficient mechanism for increasing the drought stress tolerance of maize
      seedlings.

PMID- 30183771
TI  - Ferulic acid and PDMS modified medical carbon materials for artificial joint
      prosthesis.
AB  - Medical carbon material has been extensively studied due to their excellent
      biological and mechanical properties. However, the dissociation of the surface
      carbon particles greatly limited the application of medical carbon material
      (MCM). To overcome this defect, we introduced the polydimethylsiloxane, a polymer
      coating material (PCM) that possesses acceptable biocompatibility, into medical
      carbon material to prevent the shedding of carbon debris. Additionally, to reduce
      inflammatory reactions and increase surface hydrophilicity, ferulic acid, also
      called Chinese medicine coating material (CCM), was used to modify the surface of
      polymer-coating material. We investigated the proliferation and adhesion of NIH
      3T3 cells onto MCM, PCM and CCM in vitro. We showed that CCM exhibited excellent
      biological activity to promote cell growth. Twelve weeks after CCM implantation,
      bone defects were repaired, and the material showed acceptable chemical
      stability. The results indicated that the CCM composite possesses excellent
      mechanical property and favorable biocompatibility, which can be used for
      clinical bone repair.

PMID- 30183772
TI  - Attachment buffers the physiological impact of social exclusion.
AB  - Attachment systems facilitate coping with stress, with previous studies
      demonstrating attachment figures diminishing subjective, behavioral and neural
      responses to social pain. Yet little is known about the physiological mechanisms
      governing this benefit in the context of social exclusion. This study
      investigated the impact of attachment (vs non-attachment) priming on affective
      and cardiovascular responses to social exclusion induced by the computerized
      "Cyberball" ball-tossing game, and the moderating influence of individual
      differences in attachment style, rejection sensitivity and self-construal. No
      significant change in high frequency heart rate variability (HF-HRV)-an index of
      parasympathetic activity and cardiovagal balance-was observed across the time
      course in the attachment priming condition, whereas the non-attachment condition
      showed significant fluctuation in HF-HRV-increasing during Cyberball and
      decreasing relative to baseline during recovery. Moreover, the benefit afforded
      by attachment priming on was enhanced amongst participants with lower rejection
      sensitivity and higher collectivistic self-construal, and those with higher
      anxious attachment style in the non-attachment prime group showed a trend towards
      increased HF-HRV during the Cyberball. Results are consistent with Social
      Baseline Theory, which argues that social proximity-particularly from attachment
      figures-protects against the metabolic costs associated with strong reactions to
      stress, including the preservation of cardiovagal homeostasis in this instance.
      Social attachments may provide an important mechanism to increase adaptive
      responding to the distressing experience of social exclusion.

PMID- 30183773
TI  - Side-by-side biochemical comparison of two lytic polysaccharide monooxygenases
      from the white-rot fungus Heterobasidion irregulare on their activity against
      crystalline cellulose and glucomannan.
AB  - Our comparative studies reveal that the two lytic polysaccharide monooxygenases
      HiLPMO9B and HiLPMO9I from the white-rot conifer pathogen Heterobasidion
      irregulare display clear difference with respect to their activity against
      crystalline cellulose and glucomannan. HiLPMO9I produced very little soluble
      sugar on bacterial microcrystalline cellulose (BMCC). In contrast, HiLPMO9B was
      much more active against BMCC and even released more soluble sugar than the H.
      irregulare cellobiohydrolase I, HiCel7A. Furthermore, HiLPMO9B was shown to
      cooperate with and stimulate the activity of HiCel7A, both when the BMCC was
      first pretreated with HiLPMO9B, as well as when HiLPMO9B and HiCel7A were added
      together. No such stimulation was shown by HiLPMO9I. On the other hand, HiLPMO9I
      was shown to degrade glucomannan, using a C4-oxidizing mechanism, whereas no
      oxidative cleavage activity of glucomannan was detected for HiLPMO9B. Structural
      modeling and comparison with other glucomannan-active LPMOs suggest that
      conserved sugar-interacting residues on the L2, L3 and LC loops may be essential
      for glucomannan binding, where 4 out of 7 residues are shared by HiLPMO9I, but
      only one is found in HiLPMO9B. The difference shown between these two H.
      irregulare LPMOs may reflect distinct biological roles of these enzymes within
      deconstruction of different plant cell wall polysaccharides during fungal
      colonization of softwood.

PMID- 30183774
TI  - Population structure and gene flow of the tropical seagrass, Syringodium
      filiforme, in the Florida Keys and subtropical Atlantic region.
AB  - Evaluating genetic diversity of seagrasses provides insight into reproductive
      mode and adaptation potential, and is therefore integral to broader conservation
      strategies for coastal ecosystems. In this study, we assessed genetic diversity,
      population structure and gene flow in an opportunistic seagrass, Syringodium
      filiforme, in the Florida Keys and subtropical Atlantic region. We used
      microsatellite markers to analyze 20 populations throughout the Florida Keys,
      South Florida, Bermuda and the Bahamas primarily to understand how genetic
      diversity of S. filiforme partitions across the Florida Keys archipelago. We
      found low allelic diversity within populations, detecting 35-106 alleles across
      all populations, and in some instances moderately high clonal diversity (R = 0.04
      0.62). There was significant genetic differentiation between Atlantic and Gulf of
      Mexico (Gulf) populations (FST = 0.109 +/- 0.027, p-value = 0.001) and evidence
      of population structure based on cluster assignment, dividing the region into two
      major genetic demes. We observed asymmetric patterns in gene flow, with a few
      instances in which there was higher than expected gene flow from Atlantic to Gulf
      populations. In South Florida, clustering into Gulf and Atlantic groups indicate
      dispersal in S. filiforme may be limited by historical or contemporary geographic
      and hydrologic barriers, though genetic admixture between populations suggests
      exchange may occur between narrow channels in the Florida Keys, or has occurred
      through other mechanisms in recent evolutionary history, maintaining regional
      connectivity. The variable genotypic diversity, low genetic diversity and
      evidence of population structure observed in populations of S. filiforme resemble
      the population genetics expected for a colonizer species.

PMID- 30183776
TI  - Correction: A combinatorial analysis using observational data identifies species
      that govern ecosystem functioning.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0201135.].

PMID- 30183775
TI  - Phenotypic diversity and drug susceptibility of Trypanosoma cruzi TcV clinical
      isolates.
AB  - Trypanosoma cruzi is a genetically heterogeneous group of organisms that cause
      Chagas disease. It has been long suspected that the clinical outcome of the
      disease and response to therapeutic agents are, at least in part, related to the
      genetic characteristics of the parasite. Herein, we sought to validate the
      significance of the genotype of T. cruzi isolates recovered from patients with
      different clinical forms of Chagas disease living in Argentina on their
      biological behaviour and susceptibility to drugs. Genotype identification of the
      newly established isolates confirmed the reported predominance of TcV, with a
      minor frequency of TcI. Epimastigote sensitivity assays demonstrated marked
      dissimilar responses to benznidazole, nifurtimox, pentamidine and
      dihydroartemisinin in vitro. Two TcV isolates exhibiting divergent response to
      benznidazole in epimastigote assays were further tested for the expression of
      anti-oxidant proteins. Benznidazole-resistant BOL-FC10A epimastigotes had
      decreased expression of Old Yellow Enzyme and cytosolic superoxide dismutase, and
      overexpression of mitochondrial superoxide dismutase and tryparedoxin- 1,
      compared to benznidazole-susceptible AR-SE23C parasites. Drug sensitivity assays
      on intracellular amastigotes and trypomastigotes reproduced the higher
      susceptibility of AR-SE23C over BOL-FC10A parasites to benznidazole observed in
      epimastigotes assays. However, the susceptibility/resistance profile of
      amastigotes and trypomastigotes to nifurtimox, pentamidine and dihydroartemisinin
      varied markedly with respect to that of epimastigotes. C3H/He mice infected with
      AR-SE23C trypomastigotes had higher levels of parasitemia and mortality rate
      during the acute phase of infection compared to mice infected with BOL-FC10A
      trypomastigotes. Treatment of infected mice with benznidazole or nifurtimox was
      efficient to reduce patent parasitemia induced by either isolate. Nevertheless,
      qPCR performed at 70 dpi revealed parasite DNA in the blood of mice infected with
      AR-SE23C but not in BOL-FC10A infected mice. These results demonstrate high level
      of intra-type diversity which may represent an important obstacle for the testing
      of chemotherapeutic agents.

PMID- 30183778
TI  - Feasibility of gadoxetate disodium enhanced 3D T1 MR cholangiography (MRC) with a
      specific inversion recovery prepulse for the assessment of the hepatobiliary
      system.
AB  - AIM: To compare the potential of a gadoxetate disodium enhanced navigator
      triggered 3D T1 magnetic-resonance cholangiography (MRC) sequence with a specific
      inversion recovery prepulse to T2-weighted MRCP for assessment of the
      hepatobiliary system. MATERIALS AND METHODS: 30 patients (12 male, 18 female)
      prospectively underwent conventional navigator-triggered 3D turbo spin-echo T2
      weighted MRCP and 3D T1 MRC with a specific inversion pulse to minimise signal
      from the liver 30 minutes after administration of gadoxetate disodium on a 1.5 T
      MRI system. For qualitative evaluation, biliary duct depiction was assessed
      segmentally following a 5-point Likert scale. Visualisation of hilar structures
      as well as image quality was recorded. Additionally, the extrahepatic bile ducts
      were assessed quantitatively by calculation of signal-to-noise ratios (SNR).
      RESULTS: The advantages of T1 3D MRC include reduced affection of image quality
      by bowel movement and robust depiction of the relative position of the
      extrahepatic bile ducts in relation to the portal vein and the duodenum compared
      to T2 MRCP. However, overall T1 3D MRC did not significantly (p > 0.05) improve
      the biliary duct depiction compared to T2 MRCP in all segments: Common bile duct
      4.1 vs. 4.4, right hepatic duct 3.6 vs. 4.2, left hepatic duct 3.5 vs. 4.1. Image
      quality did not differ significantly (p > 0.05) between both sequences (3.6 vs.
      3.5). SNR measurements for the hepatobiliary system did not differ significantly
      (p > 0.05) between navigator-triggered T1 3D MRC and T2 MRCP. CONCLUSIONS: This
      preliminary study demonstrates that T1 3D MRC of a specific inversion recovery
      prepulse has potential to complement T2 MRCP, especially for the evaluation of
      liver structures close to the hilum in the diagnostic work-up of the biliary
      system in patients receiving gadoxetate disodium.

PMID- 30183777
TI  - Novel coronavirus-like particles targeting cells lining the respiratory tract.
AB  - Virus like particles (VLPs) produced by the expression of viral structural
      proteins can serve as versatile nanovectors or potential vaccine candidates. In
      this study we describe for the first time the generation of HCoV-NL63 VLPs using
      baculovirus system. Major structural proteins of HCoV-NL63 have been expressed in
      tagged or native form, and their assembly to form VLPs was evaluated.
      Additionally, a novel procedure for chromatography purification of HCoV-NL63 VLPs
      was developed. Interestingly, we show that these nanoparticles may deliver cargo
      and selectively transduce cells expressing the ACE2 protein such as ciliated
      cells of the respiratory tract. Production of a specific delivery vector is a
      major challenge for research concerning targeting molecules. The obtained results
      show that HCoV-NL63 VLPs may be efficiently produced, purified, modified and
      serve as a delivery platform. This study constitutes an important basis for
      further development of a promising viral vector displaying narrow tissue tropism.

PMID- 30183779
TI  - The relationship between depression and cognitive function in adults with
      cardiovascular risk: Evidence from a randomised attention-controlled trial.
AB  - BACKGROUND AND AIM: This study assessed the association between depressive
      symptom severity and cognition in middle-to-older aged adults with mild-to
      moderate depression and cardiovascular risk factors using an online test battery
      (CogState) and whether changes in depressive symptoms over 3 months were
      associated with changes in cognition. METHODS: Participants (mean age = 57.8)
      with cardiovascular risk and mild-to-moderate depressive symptoms completed
      measures of psychomotor speed, learning, and executive function prior to (n =
      445)_and after (n = 334) online depression or attention control interventions.
      The symptom severity-cognition relationship was examined both cross-sectionally
      and prospectively. RESULTS: Participants exhibited significantly reduced
      psychomotor speed and variable impairments on measures of learning and executive
      functioning relative to normative data. However, there was no association of
      depression severity with cognition at baseline or of change in depressive
      symptoms with change in cognitive performance. LIMITATIONS: Participants were
      well-educated, which may have protected against cognitive decline. Attrition may
      limit generalisability, though is unlikely to explain the lack of association
      between depression symptoms and cognition. CONCLUSIONS: Adults with comorbid mild
      to-moderate depressive symptoms and cardiovascular risks performed less well than
      age-matched normative data on three online cognitive tests; however, we were
      unable to show any symptom-cognition association cross-sectionally or
      longitudinally, despite significant improvements in depressive symptoms. This
      challenges the generalisability of such associations found in more severely
      unwell clinical samples to those with a broader depressive symptom profile, or
      suggests that underlying cardiovascular disease may account for the association
      seen in some clinical studies. This has implications for scaling up selective
      prevention of cognitive decline.

PMID- 30183780
TI  - Listening to yourself is special: Evidence from global speech rate tracking.
AB  - Listeners are known to use adjacent contextual speech rate in processing
      temporally ambiguous speech sounds. For instance, an ambiguous vowel between
      short /alpha/ and long /a:/ in Dutch sounds relatively long (i.e., as /a:/)
      embedded in a fast precursor sentence, but short in a slow sentence. Besides the
      local speech rate, listeners also track talker-specific global speech rates.
      However, it is yet unclear whether other talkers' global rates are encoded with
      reference to a listener's self-produced rate. Three experiments addressed this
      question. In Experiment 1, one group of participants was instructed to speak
      fast, whereas another group had to speak slowly. The groups were compared on
      their perception of ambiguous /alpha/-/a:/ vowels embedded in neutral rate speech
      from another talker. In Experiment 2, the same participants listened to playback
      of their own speech and again evaluated target vowels in neutral rate speech.
      Neither of these experiments provided support for the involvement of self
      produced speech in perception of another talker's speech rate. Experiment 3
      repeated Experiment 2 but with a new participant sample that was unfamiliar with
      the participants from Experiment 2. This experiment revealed fewer /a:/ responses
      in neutral speech in the group also listening to a fast rate, suggesting that
      neutral speech sounds slow in the presence of a fast talker and vice versa. Taken
      together, the findings show that self-produced speech is processed differently
      from speech produced by others. They carry implications for our understanding of
      rate-dependent speech perception in dialogue settings, suggesting that both
      perceptual and cognitive mechanisms are involved.

PMID- 30183781
TI  - New insights into mechanisms of enhanced synaesthetic memory: Benefits are
      synaesthesia-type-specific.
AB  - The goal of this study was to test the nature of the memory advantage in
      synaesthesia. We compared four different types of synaesthetes (27 grapheme
      colour, 21 sound-colour-, 25 grapheme-colour-and-sound-colour- and 24 sequence
      space synaesthetes) to their matched controls. Recognition memory for three types
      of stimuli (music, words, colour) was tested. We anticipated a general advantage
      in memory for synaesthetes and potentially additional synaesthesia-specific
      benefits. The results showed a general advantage for synaesthesia. Further, a
      benefit for colour stimuli resulted for grapheme-colour synaesthetes and a
      benefit for music stimuli resulted for grapheme-colour-and-sound-colour
      synaesthetes, indicating synaesthesia-type specific effects. These results
      suggest different mechanisms for the explanation of the memory benefit for
      different types of synaesthesia such as synaesthesia-related colour expertise for
      grapheme-colour synaesthesia and additional encoding opportunities for grapheme
      colour-and-sound-colour synaesthesia.

PMID- 30183782
TI  - Muscle glycogen concentrations and response to diet and exercise regimes in
      Warmblood horses with type 2 Polysaccharide Storage Myopathy.
AB  - Type 1 polysaccharide storage myopathy (PSSM1) is a glycogen storage disorder of
      known cause whereas the basis for type 2 PSSM (PSSM2) is unknown. The same diet
      and exercise regime prescribed for PSSM1 is recommended for PSSM2; however, the
      benefit of these recommendations for PSSM2 is undocumented. The objectives of
      this study were to determine traits of PSSM2 Warmblood horses (WB), determine the
      changes in exercise responses that occur with a recommended low-starch/fat
      supplemented diet and exercise regime, and determine if glycogen concentrations
      correspond to the severity of signs. Owners of PSSM2 WB (2008-2016), completed a
      retrospective questionnaire regarding their horse. Glycogen concentrations were
      analyzed in skeletal muscle of PSSM2 WB (n = 36) obtained prior to
      recommendations and in control WB with no evident myopathy (n = 23). Chi-square,
      Fisher's exact, McNemar's tests with Bonferroni correction and Mann Whitney
      testing were utilized. Abnormal exercise responses reported by owners, began at
      approximately 6 years of age and included a decline in performance, a reluctance
      to collect and reluctance to go forward in over 50% of horses. With the
      recommended diet and exercise regime, 80% of PSSM2 WB owners reported an overall
      improvement with significant decreases in the proportion of horses showing a
      decline in performance and rhabdomyolysis. However, 53% of PSSM2 WB were still
      not advancing as expected with reluctance to go forward and collect persisting in
      approximately one third of horses. Median muscle glycogen concentrations did not
      differ between PSSM2 WB and WB with no evident myopathy. PSSM2 WB with the
      highest glycogen concentrations were significantly more likely to show a decline
      in performance than those with lower glycogen concentrations. In conclusion, diet
      and exercise recommendations ideal for PSSM1 improve but do not eliminate the
      decline in performance and reluctance to go forward under saddle characteristic
      of PSSM2.

PMID- 30183784
TI  - Erratum.
AB  - [This corrects the article DOI: 10.1080/21501203.2018.1492981.].

PMID- 30183783
TI  - Dynamic image denoising for voxel-wise quantification with Statistical Parametric
      Mapping in molecular neuroimaging.
AB  - PURPOSE: PET and SPECT voxel kinetics are highly noised. To our knowledge, no
      study has determined the effect of denoising on the ability to detect differences
      in binding at the voxel level using Statistical Parametric Mapping (SPM).
      METHODS: In the present study, groups of subject-images with a 10%- and 20%-
      difference in binding of [123I]iomazenil (IMZ) were simulated. They were denoised
      with Factor Analysis (FA). Parametric images of binding potential (BPND) were
      produced with the simplified reference tissue model (SRTM) and the Logan non
      invasive graphical analysis (LNIGA) and analyzed using SPM to detect group
      differences. FA was also applied to [123I]IMZ and [11C]flumazenil (FMZ) clinical
      images (n = 4) and the variance of BPND was evaluated. RESULTS: Estimations from
      FA-denoised simulated images provided a more favorable bias-precision profile in
      SRTM and LNIGA quantification. Simulated differences were detected in a higher
      number of voxels when denoised simulated images were used for voxel-wise
      estimations, compared to quantification on raw simulated images. Variability of
      voxel-wise binding estimations on denoised clinical SPECT and PET images was also
      significantly diminished. CONCLUSION: In conclusion, noise removal from dynamic
      brain SPECT and PET images may optimize voxel-wise BPND estimations and detection
      of biological differences using SPM.

PMID- 30183785
TI  - Anionic uranyl oxyfluorides as a bifunctional platform for highly selective ion
      exchange and photocatalytic degradation of organic dyes.
AB  - Uranium is unique owing not only to its intriguing physiochemical properties, but
      also to the diverse coordination chemistry that uranyl adopts and bonding that
      enables rich and unpredictable topologies of uranium-bearing materials. Six
      anionic uranium oxyfluorides with various dimensionalities, including a 3D
      framework (MeUF), four 2D lamellar structures (EtUF-1, PrUF, BuUF-1, and BuUF-2),
      and a 1D chained topology (EtUF-2), have been rationally constructed by employing
      tetra-alkyl ammonium ions as structure-directing agents. By combining the tunable
      interlayer distance of the lamellar structures with the photooxygenation
      properties of uranyl ions, a bifunctional platform for highly selective ion
      exchange and photocatalytic degradation over organic dyes has been developed.
      Specifically, BuUF-2 can efficiently capture 94.5% methylene blue (MB+) within 24
      h from solution with remarkable selectivity related to both the size and the
      charge of organic dyes. Such size- and charge-dependent selectivity toward
      organic dyes has been documented for MOFs, but is rare for 2D lamellar materials.
      Furthermore, the removal of MB+ can be largely accelerated under UV radiation
      (e.g. 84.7% for BuUF-2 within 1 h) due to the photocatalytic activities of EtUF
      1, EtUF-2, PrUF, and BuUF-2.

PMID- 30183786
TI  - Dietary chlorogenic acid supplementation affects gut morphology, antioxidant
      capacity and intestinal selected bacterial populations in weaned piglets.
AB  - Chlorogenic acid (CGA), an ester formed between caffeic acid and quinic acid, is
      one of the most abundant phenolic acids and is widespread in fruits, vegetables,
      cereals and tuber crops. Therefore, the present study was conducted to test the
      hypothesis that dietary supplementation with CGA could improve intestinal health
      and regulate intestinal selected microbiota in weaned piglets. A total of twenty
      four piglets (21 d of age) were randomly assigned to one of four groups according
      to their initial BW and sex and fed a basal diet (control group) or a basal diet
      containing 250, 500 and 1000 mg kg-1 CGA, respectively. The whole trial lasted
      for 28 d. Dietary CGA supplementation increased (P < 0.05) the duodenal villous
      height and villous height : crypt depth ratio, but decreased (P < 0.05) the F/G
      ratio and duodenal crypt depth when compared with the control group. Meanwhile,
      an increase (P < 0.05) in the jejunal villous height and in the ileal villous
      height : crypt depth ratio were also observed in CGA-fed piglets. Supplementation
      with CGA significantly increased (P < 0.05) the activity of serum GSH-Px and the
      activities of duodenal GSH-Px and CAT, upregulated (P < 0.05) the expression of
      OCLN in the duodenum and jejunum, and decreased (P < 0.05) the ileal MDA content
      when compared to the control group. In addition, an increase (P < 0.05) in the
      population of Lactobacillus and a decrease (P < 0.05) in the population of
      Escherichia coli were observed in the colon of pigs fed CGA diets. Furthermore,
      pigs fed CGA diets had higher (P < 0.05) propionic and butyric acid
      concentrations in the colon. Altogether, our results provide evidence that
      dietary CGA is beneficial for preserving intestinal morphological integrity and
      selectively regulating intestinal microbiota, which can provide a means to
      improve gut health and growth performance post-weaning.

PMID- 30183787
TI  - Chromium complexes supported by the bidentate PN ligands: synthesis,
      characterization and application for ethylene polymerization.
AB  - Chromium-based complexes are among the most important catalysts in the field of
      ethylene polymerization and oligomerization. Heterogeneous Cr Phillips catalysts
      account for more than one-third of the commercialized high density polyethylene
      (HDPE). In this contribution, chromium complexes, LCrCl3 (Cr1-Cr4: L = 2,6-R1-4
      R2-C6H2-N[double bond, length as m-dash]CH-C6H4-2-PPh2; Cr1: R1 = H, R2 = H; Cr2:
      R1 = Me, R2 = H; Cr3: R1 = iPr, R2 = H; Cr4: R1 = Ph2CH, R2 = iPr), have been
      synthesized and characterized by elemental analysis, ESI and IR spectroscopy. The
      molecular structures of Cr3 and Cr4 are defined by X-ray diffraction, revealing a
      distorted octahedral geometry around the chromium center in both structures. In
      the presence of an aluminum cocatalyst, complexes Cr1-Cr4 show moderate to high
      activities toward ethylene polymerization. The nature of the catalysts and
      various reaction conditions, such as the nature and the amount of cocatalyst,
      reaction time and temperature, are investigated in detail. The results show that
      the title complexes have good thermal stability and the substituents on the
      ligands significantly affect the catalytic properties. Particularly, complex Cr4
      can produce HDPE with a high molecular weight up to 68.3 * 104 g mol-1 due to the
      suppression of the chain transfer/termination by the introduction of bulky Ph2CH
      groups.

PMID- 30183788
TI  - Visible light-induced aerobic oxidative cross-coupling of glycine esters with
      alpha-angelicalactone: a facile pathway to gamma-lactams.
AB  - A metal-free aerobic oxidative dehydrogenative formal [2 + 3] cyclization of
      glycine esters with alpha-angelicalactone has been accomplished via the
      synergistic combination of photoredox catalysis and acid catalysis. This protocol
      provides straightforward and facile access to a series of substituted gamma
      lactams at room temperature under an air atmosphere. Moreover, the reaction could
      be carried out on a gram scale. The mild conditions as well as the use of cheap
      substrates and catalyst make this protocol very attractive for further synthetic
      applications.

PMID- 30183790
TI  - Tacrine-deferiprone hybrids as multi-target-directed metal chelators against
      Alzheimer's disease: a two-in-one drug.
AB  - Alzheimer's disease (AD) is a severe age-dependent neurodegenerative disorder
      affecting several million people worldwide. So far, there is no adequate
      medication to prevent or slow down the progression of the disease, only
      medication with palliative effects allowing temporary symptomatic reliefs. As
      part of our continuing efforts into the development of innovative drugs following
      a polypharmacological strategy, we decided to use a former anti-AD palliative
      drug (tacrine) and to reposition it by hybridization with a metal chelating drug
      (deferiprone, DFP). This combination endows the hybrids with good capacity to
      inhibit acetylcholinesterase (low micromolar range) and self-/Cu-induced Abeta
      aggregation (up to ca. 90%) as well as a good radical scavenging ability
      (micromolar range) and metal (M) chelating capacity, with pM (pM = -log[M], CL/CM
      = 10, CM = 10-6 M at pH = 7.4, M = Fe, Cu, Zn) values close to those of DFP. The
      most promising compounds have 2-hydroxypropyl linkers, and a selection of
      compounds have demonstrated neuroprotective roles in neuroblastoma cells treated
      with Abeta1-42 and ascorbate/iron stressors. Consequently, these hybrids can be
      considered as attractive multipotent therapeutic molecules that will eventually
      play key roles against AD progression, namely in the control of cholinergic
      dysfunction, amyloid peptide aggregation, oxidative stress, and metal modulation,
      besides presenting a good pharmacokinetic profile.

PMID- 30183791
TI  - Cadmium associates with oxalate in calcium oxalate crystals and competes with
      calcium for translocation to stems in the cadmium bioindicator Gomphrena
      claussenii.
AB  - Cadmium (Cd) was shown to co-localise with calcium (Ca) in oxalate crystals in
      the stems and leaves of Cd tolerant Gomphrena claussenii, but Cd binding remained
      unresolved. Using synchrotron radiation X-ray absorption near edge spectroscopy
      we demonstrate that in oxalate crystals of hydroponically grown G. claussenii the
      vast majority of Cd is bound to oxygen ligands in oxalate crystals (>88%; Cd-O-C
      coordination) and the remaining Cd is bound to sulphur ligands (Cd-S-C
      coordination). Cadmium binding to oxalate does not depend on the amount of Ca
      supplied or from which organs the crystals originate (stems and mature leaves).
      By contrast, roots contain no oxalate crystals and therein Cd is bound
      predominantly by S ligands. The potential to remove Cd by extraction of Cd-rich
      oxalate crystals from plant material should be tested in phytoextraction or
      phytomining strategies.

PMID- 30183792
TI  - Morita-Baylis-Hillman reaction of a chiral aziridine aldehyde.
AB  - The Morita-Baylis-Hillman reaction of (R)-1-((R)-1-phenylethyl)aziridine-2
      carbaldehyde with alkyl acrylate was carried out under various conditions by
      changing solvents, bases, and alcohol additives. The reaction at room temperature
      under neat conditions (no solvent) with quinuclidine as an amine nucleophile, in
      the presence of benzyl alcohol as an additive, afforded a product, gamma
      (aziridin-2-yl)-beta-hydroxy-alpha-methylene butanoate, in 97% yield with a
      diastereomeric ratio of anti and syn as 86 : 14.

PMID- 30183789
TI  - 3D microfluidic ex vivo culture of organotypic tumor spheroids to model immune
      checkpoint blockade.
AB  - Microfluidic culture has the potential to revolutionize cancer diagnosis and
      therapy. Indeed, several microdevices are being developed specifically for
      clinical use to test novel cancer therapeutics. To be effective, these platforms
      need to replicate the continuous interactions that exist between tumor cells and
      non-tumor cell elements of the tumor microenvironment through direct cell-cell or
      cell-matrix contact or by the secretion of signaling factors such as cytokines,
      chemokines and growth factors. Given the challenges of personalized or precision
      cancer therapy, especially with the advent of novel immunotherapies, a critical
      need exists for more sophisticated ex vivo diagnostic systems that recapitulate
      patient-specific tumor biology with the potential to predict response to immune
      based therapies in real-time. Here, we present details of a method to screen for
      the response of patient tumors to immune checkpoint blockade therapy, first
      reported in Jenkins et al. Cancer Discovery, 2018, 8, 196-215, with updated
      evaluation of murine- and patient-derived organotypic tumor spheroids
      (MDOTS/PDOTS), including evaluation of the requirement for 3D microfluidic
      culture in MDOTS, demonstration of immune-checkpoint sensitivity of PDOTS, and
      expanded evaluation of tumor-immune interactions using RNA-sequencing to infer
      changes in the tumor-immune microenvironment. We also examine some potential
      improvements to current systems and discuss the challenges in translating such
      diagnostic assays to the clinic.

PMID- 30183793
TI  - Controlling methylene blue aggregation: a more efficient alternative to treat
      Candida albicans infections using photodynamic therapy.
AB  - Methylene Blue (MB) has been widely used in antimicrobial Photodynamic Therapy
      (aPDT), however, the mechanisms of action (Type I or Type II) are defined by its
      state of aggregation. In this sense, the identification of the relationships
      between aggregation, the mechanisms of action and the effectiveness against
      microorganisms, as well as the establishment of the means and the formulations
      that may favor the most effective mechanisms, are essential. Thus, the objective
      of this study was to assess the in vitro aPDT efficacies against Candida
      albicans, by using MB in vehicles which may influence the aggregation and present
      an oral formulation (OF) containing MB, to be used in clinical aPDT procedures.
      The efficacy of MB at 20 mg L-1 was tested in a range of vehicles (water,
      physiological solution - NaCl 0.9%, phosphate saline buffer - PBS, sodium dodecyl
      sulfate 0.25% - SDS and urea 1 mol L-1) in a C. albicans planktonic culture, when
      using 4.68 J cm-2 of 640 +/- 12 nm LED for the irradiations, as well as 5 minutes
      of pre-irradiation time, together with measuring the UFC mL-1. Based upon these
      analyses, an OF containing MB in the most effective vehicle was tested in the
      biofilms, as a proposal for clinical applications. When comparing some of the
      vehicles, sodium dodecyl sulfate was the only one that enhanced an MB aPDT
      efficacy in a planktonic C. albicans culture. This OF was tested in the biofilms
      and 50 mg L-1 MB was necessary, in order to achieve some reduction in the cell
      viabilities after the various treatments. The light dosimetries still need
      further adaptations, in order for this formulation to be used in clinical
      applications. The present research has indicated that the development of this
      formulation for the control of MB aggregations may result in more effective
      clinical protocols.

PMID- 30183794
TI  - High-Q, low-mode-volume and multiresonant plasmonic nanoslit cavities fabricated
      by helium ion milling.
AB  - Helium ion milling of chemically-synthesized micron-sized gold flakes is
      performed to fabricate ultra-narrow nanoslit cavities with a varying length and
      width down to 5 nm. Their plasmon resonances are characterized by one-photon
      photoluminescence spectroscopy. The combination of fabrication based on single
      crystalline gold and resonant modes with low radiative losses leads to remarkably
      high quality factors of up to 24. Multiple Fabry-Perot-type resonances in the
      visible/near infrared spectral range are observed due to the achieved narrow slit
      widths and the resulting short effective wavelengths of nanoslit plasmons. These
      features make nanoslit cavities attractive for a range of applications such as
      surface-enhanced spectroscopy, ultrafast nano-optics and strong light-matter
      coupling.

PMID- 30183795
TI  - Synthesis and characterization of a series of transition metal oxychlorides:
      MBi(SeO3)2(H2O)Cl (M = Co, Ni, Cu).
AB  - Three new transition metal oxychlorides MBi(SeO3)2(H2O)Cl (M = Co, Ni, Cu) have
      been firstly synthesized through a hydrothermal reaction method at 200  degrees
      C. They were structurally determined to be isostructural with the Pbca space
      group of the orthorhombic system. They feature a 3D framework topology with two
      dimensional tunnels intersected and filled with Cl anions parallel to the
      crystallographic bc-plane. Two neighboring MO5Cl octahedra are connected by a
      sharing edge into a M2O8Cl2 dimer which serves as the structural knots to knit
      the 2D [Bi(SeO3)2]infinity layers in the ab-plane together into the total 3D
      crystal architecture. The optical band gaps of CoBi(SeO3)2(H2O)Cl (1),
      NiBi(SeO3)2(H2O)Cl (2) and CuBi(SeO3)2(H2O)Cl (3) were evaluated to be 3.7 eV,
      3.5 eV and 3.2 eV, respectively, through extrapolating the UV-vis-NIR optical
      absorption spectra. Besides, the spin-allowed d-d transition absorption spectra
      of the transition ion centers are observed in three compounds exhibiting
      different colors. Compounds 1, 2 and 3 can stay thermally stable below 370 
      degrees C, 400  degrees C and 300  degrees C, respectively, as found from the
      results of thermal analysis based on the simultaneous thermogravimetry and
      differential scanning calorimetry techniques. 1, 2 and 3 exhibit
      antiferromagnetic properties below Neel temperatures 6 K, 18 K and 52 K,
      respectively. Above the Neel temperatures, Curie-Weiss behavior dominates in the
      M-T process for the three compounds. The cell parameters are listed: a = 14.056
      A, b = 7.582 A, c = 14.996 A, and Z = 8 for 1, a = 14.083 A, b = 7.575 A, c =
      14.860 A, and Z = 8 for 2, and a = 14.576 A, b = 7.371 A, c = 14.656 A, and Z = 8
      for 3.

PMID- 30183796
TI  - Pyridoxal phosphate-dependent reactions in the biosynthesis of natural products.
AB  - Covering: up to mid-2018Pyridoxal 5'-phosphate (PLP) is a versatile organic
      cofactor used to catalyze diverse reactions on amino acid, oxoacid, and amine
      substrates. Here we review the reactions catalyzed by PLP-dependent enzymes,
      highlighting enzymes reported in the natural product biosynthetic literature. We
      describe enzymes that catalyze transaminations, Claisen-like condensations, and
      beta- and gamma-eliminations and substitutions, along with epimerizations,
      decarboxylations, and transaldolations. Finally, we describe a newly reported
      group of O2-, PLP-dependent enzymes. Altogether, natural product biosynthesis
      showcases the incredible versatility of PLP-dependent transformations for
      building chemical complexity.

PMID- 30183797
TI  - Palladium alkyl complexes with a formazanate ligand: synthesis, structure and
      reactivity.
AB  - Palladium(ii) complexes with a bidentate, anionic formazanate ligand are
      described. Attempts to prepare mono(formazanate) palladium alkyl complexes often
      leads to the homoleptic bis(formazanate) complex, which shows rich
      electrochemistry due to the redox-active nature of the ligands. Performing salt
      metathesis between the precursor [Pd(COD)(CH3)Cl] and the potassium salt of the
      ligand in the presence of tetrabutylammonium chloride yields a square planar
      mono(formazanate) palladate complex through coordination of chloride anion.
      Ligand exchange allows binding of unsaturated molecules and evaluation of the
      reactivity of the Pd-CH3 fragment. Using this approach, insertion reactions of
      CO, isocyanide and methyl acrylate into the Pd-CH3 bond are demonstrated.

PMID- 30183798
TI  - Correction: Stepwise triple-click functionalization of synthetic peptides.
AB  - Correction for 'Stepwise triple-click functionalization of synthetic peptides' by
      Anna Kovalova et al., Org. Biomol. Chem., 2018, 16, 5960-5964.

PMID- 30183799
TI  - Copper-catalyzed C-N bond formation with imidazo[1,2-a]pyridines.
AB  - An efficient Cu-catalyzed method for direct C-N bond formation on the C-3
      position of imidazo[1,2-a]pyridines is reported. The robust copper catalyst
      tolerated a wide range of functional groups and set the stage for the synthesis
      of diversely decorated imidazo[1,2-a]pyridines. Preliminary experimental results
      show that the reaction mechanism is consistent with C-3 radical
      functionalization.

PMID- 30183800
TI  - Organic dye-photocatalyzed fluoroalkylation of heteroarene-N-oxide derivatives.
AB  - The first direct CHet-H perfluoroalkylation reaction of heteroaromatic-N-oxides
      has been achieved through a visible light-photocatalyzed reaction in the presence
      of commercially available perfluoroalkyl iodides RF-I and base in DMF as solvent
      and Rose Bengal as organic photocatalyst. The reactions proceed in the absence of
      transition metals and can be scaled up. Through an acid-catalyzed transformation
      of the perfluoroalkylated-N-oxides thus obtained, the first direct syntheses of 2
      (perfluoroalkyl)benzo[f][1,3]oxazepines are achieved. De-oxygenation of the
      resulting perfluoroalkylated heteroaromatic-N-oxides leads to high yielding and
      regioselective radical perfluoroalkylation protocols of heteroaromatic compounds.
      To the best of our knowledge, this is the first report on a direct method for
      perfluoroalkylation of pyridine-, quinoline-, and diazine-N-oxide derivatives.

PMID- 30183801
TI  - Evaluation of postoperative complications in elderly patients submitted to
      parotidectomy.
AB  - OBJECTIVE: to evaluate the most incident histological subtypes and the main
      postoperative complications in elderly patients with parotid tumors submitted to
      parotidectomy. METHODS: we conducted a retrospective study with 57 elderly
      patients submitted to parotidectomy from 2003 to 2017, at the Sao Jose County
      Hospital of Joinville, Santa Catarina, Brazil. RESULTS: thirty-three (57.9%)
      patients had benign tumors, the most frequent being Warthin's tumor, and 17
      (29.8%), malignant tumors, squamous cell carcinoma being the most frequent. Seven
      patients (12.3%) presented clinical complications, arterial pressure instability
      and respiratory complications being the most frequent, in four (7%) and three
      (5.3%) cases, respectively. Thirteen (22.1%) patients presented complications
      related to the surgical wound, hematoma and wound infection being the most
      frequent, with six (10.5%) cases each. Twenty-four (42.1%) patients had some
      degree of facial nerve dysfunction in the postoperative period, Brackman-House
      grade III being the most frequent, in 11 cases (19.3%). Surgical time and
      lymphadenectomy were associated with clinical complications. The main variables
      that showed an association with surgical complications were tumor size, longer
      surgical time, reoperation, and perioperative crystalloid infusion volume.
      CONCLUSION: parotid neoplasms present a differentiated profile in the elderly
      population, especially Warthin's tumor and squamous cell carcinoma. Hematoma and
      infection of the operative wound and facial nerve lesions were the most prevalent
      complications in the postoperative period.

PMID- 30183802
TI  - ASSOCIATION OF MENINGITIS AND PERICARDITIS IN INVASIVE PNEUMOCOCCAL DISEASE: A
      RARE CASE.
AB  - OBJECTIVE: To report a rare case of a child with invasive pneumococcal disease
      that presented meningitis associated with pericarditis. CASE DESCRIPTION: This
      report describes the unfavorable clinical course of a previously healthy 6-months
      old female infant who initially presented symptoms of fever and respiratory
      problems. A chest X-ray revealed an increased cardiac area with no radiographic
      changes in the lungs. After identifying a pericardial effusion, the patient
      experienced seizures and went into coma. Pneumonia was excluded as a possibility
      during the clinical investigation. However, Streptococcus pneumoniae was
      identified in the cerebrospinal fluid and blood cultures. An initial neurological
      examination showed that the patient was brain dead, which was then later
      confirmed according to protocol. COMMENTS: Purulent pericarditis has become a
      rare complication of invasive pneumococcal disease since the advent of antibiotic
      therapy. Patients with extensive pneumonia are primarily predisposed and, even
      with early and adequate treatment, are prone to high mortality rates. The
      association of pneumococcal meningitis and pericarditis is uncommon, and
      therefore difficult to diagnose. As such, diagnostic suspicion must be high in
      order to institute early treatment and increase survival.

PMID- 30183803
TI  - CONGENITAL HYPOTHYROIDISM AS A RISK FACTOR FOR CENTRAL HEARING PROCESS DISORDERS.
AB  - OBJECTIVE: To investigate the presence of central auditory processing disorder
      symptoms in children with congenital hypothyroidism. METHODS: An exploratory,
      descriptive, cross-sectional study of 112 patients with congenital hypothyroidism
      aged >=5 years old. An interview was held with the parents/caregivers at the time
      of the medical consultation. Patients with other medical conditions were
      excluded. As a research instrument, the structured protocol of anamnesis was used
      to evaluate the auditory processing routinely used by audiologists. For
      statistical analysis, the chi-square test was used. RESULTS: Sex distribution was
      similar in both boys and girls (girls: 53.3%). The most prevalent phenotypic form
      of congenital hypothyroidism was no dysgenesis (88.4%), and 65.3% of the children
      had an episode of irregular serum thyroid-stimulating hormone (TSH) levels. Among
      the manifestations of the most frequent central auditory processing disorder
      symptoms, problems were reported with regard to cognitive functions, as they
      related to hearing, such as figure-background ability (83.0%), auditory attention
      (75.9%) and auditory memory (33.0%). Complaints related to school performance
      were reported in 62.3% of the cases. CONCLUSIONS: The data obtained show a high
      frequency of lag symptoms in cognitive functions related to central auditory
      processing, particularly with regard to auditory attention, figure-background
      ability and auditory memory in patients with congenital hypothyroidism.

PMID- 30183804
TI  - [Cost per year of potential life lost: a proposal to estimate tobacco taxation].
AB  - OBJECTIVES : Taxes are the most effective measure to reduce tobacco consumption,
      although this remains a controversial matter. This study presents a method to
      determine and justify taxation based on the monetary value of the years of
      potential life lost due to tobacco consumption. METHODS : A literature review
      allowed estimating the average reduction of life expectancy in smokers. The value
      used in cost-effectiveness studies -three times the GDP per capita (COP 16 613
      951 for 2015, equivalent to USD 6 056, applying an exchange rate of USD 1=COP
      2743) - was applied to each year lost. Considering the average years of tobacco
      consumption and the number of packs consumed during that period, the tax that
      each pack should have was estimated in such a way that, by the time the smoker
      dies, he or she will have paid for the years lost with an annual interest rate of
      3 %. RESULTS : Given an average reduction of life expectancy of 6 years, each
      smoker should contribute to the health system with COP 299 051 115 (USD 109 008).
      With an annual average consumption of 166 cigarette packs for 50 years, a smoker
      should pay each year COP 2 659 648 (USD 969), which means that each cigarette
      pack should have a tax of COP 16 022 (USD 5.84). CONCLUSIONS : If it is accepted
      that the health system has to pay up to three times the GDP per capita for each
      year of life in health interventions that add years, it is reasonable to think
      that those interventions that take away years of life should also make an
      equivalent contribution.

PMID- 30183805
TI  - [An approach to research in the political agendas of the health sector in
      Colombia between 1990 and 2010].
AB  - OBJECTIVE : To understand health research in Colombia in the context of
      governmental and legislative agendas related to the health sector between 1990
      and 2010. METHODS : Official sources were used such as development plans, bills
      and institutional documents. RESULTS : The National Government, the Ministry of
      Health and Social Protection (MSPS by its acronym in Spanish) and the Colombian
      Congress have focused their attention on health research as a public concern at
      certain presidential periods due to their interest in reducing the gap between
      research and health needs. In the 1990s, government plans showed greater interest
      in formulating a Science and Technology (S&T) policy in health led by the
      Ministry, an entity that had directorates, commissions and committees responsible
      for promoting and planning health research. In Congress, some health system
      reform projects included initiatives to formulate a health research policy that
      were not approved. DISCUSSION : Health research is recognized as a fundamental
      tool to help solve health problems. However, said recognition by governmental and
      legislative actors has not been constant and the institutionality in the health
      sector has been precarious considering that there is no permanent interest in
      formulating an S&T policy in health.

PMID- 30183806
TI  - [Metabolic syndrome and concentrations of uric acid and ultrasensitive C-reactive
      protein].
AB  - OBJECTIVE : To establish the prevalence of metabolic syndrome (MS) according to
      ATP III and its correlation with the concentration of uric acid and C-reactive
      protein (CRP) in people aged between 45 and 60, living in the Getsemani
      neighborhood of Cartagena. MATERIALS AND METHODS : Observational, descriptive
      correlational study on a population of 802 inhabitants of the Getsemani
      neighborhood of Cartagena, Colombia. A random sample of 302 inhabitants was
      analyzed with a 95% confidence interval and 5% margin of error. ATP III
      diagnostic criteria were applied, and the instrument used included basic data
      about the general context of the patient (social, demographic and economic
      aspects, family history, work activity and physical characteristics such as
      weight, waist circumference, blood pressure, and BMI), as well as diagnostic
      tests such as glycemia, total cholesterol, triglycerides, HDLc, LDLc, uric acid
      and ultra-sensitive C-reactive protein. RESULTS : The prevalence of metabolic
      syndrome in the susceptible population is 18 %. The most common metabolic
      syndrome factor is abdominal obesity with 85 %, followed by increase of
      triglycerides by 76 %. CONCLUSION : The prevalence of metabolic syndrome was
      considered high when applying ATP III criteria. No significant association was
      observed regarding CRP values and the chances of developing metabolic syndrome in
      both men and women. However, uric acid levels were correlated to the disease in
      the group of women susceptible to suffering from MS with a value of p=0.0022.

PMID- 30183807
TI  - [Frequency of metabolic syndrome and risk factors in adults with and without
      diabetes mellitus and arterial hypertension].
AB  - OBJECTIVE : Determinate the frequency and the risk factors for Metabolic Syndrome
      in adults with diabetes mellitus, Hypertension and without Diabetes-
      Hypertension. MATERIALS AND METHODS : We realized a cross-sectional study in
      patients of both sexes and older than 20 years of the "Hospital General de Zona 1
      IMSS" in Colima, Mexico. The variables studied were: age, BMI, waist
      circumference, cigarette smoking, and family history of diabetes and
      hypertension, and biochemical parameters, such as glucose, HDL cholesterol and
      triglycerides. RESULTS : A total of 417 persons were enrolled (170 men and 247
      women), with an age average of 53.2 +/- 13.4 years (age range, 20 to 86 years).
      The global frequency of the metabolic syndrome was 52.3 % (56 % in women and 46.4
      % in men). While the MS frequency was 50 % in DM2, 42 % in hypertension, 80 % in
      DM2+hypertension and 28.2 % without DM2 and hypertension. The cigarette smoking
      frequency was 27.8 %, and it was an important risk factor for the totally of
      patients with MS, in DM2 and in DM2+hypertension. CONCLUSIONS : The frequency of
      MS in adults was 52.3 %, women were the most affected, and cigarette smoking was
      the most important risk factor.

PMID- 30183808
TI  - [Changes in the physical activity of university students: association with health
      information and access to places for practicing].
AB  - OBJECTIVE : To evaluate changes in the physical activity level (PAL) of students
      within the first two years of studies and their association with access to health
      information and places for physical activity. METHODS : The sample included
      students who were admitted to the Federal University of Reconcavo in Bahia,
      Brazil, and were observed during their first two years of studies. Socioeconomic
      and demographic aspects, as well as body mass, height, health information and
      access to places for physical activity were assessed through a self-report. PAL
      was measured using the International Physical Activity Questionnaire (IPAQ) and
      classified based on the criteria of the Research Committee for IPAQ. Chi-square
      test and McNemar test (p<0.05) were used for statistical analysis. RESULTS : The
      sample that participated during the entire observation period was composed of 92
      students (64.1% female). The insufficiently active students ratio increased from
      7.6% to 12.0% during the first two years of undergraduate studies, but this
      difference was not significant (p>0.05). Students who did not receive information
      about health care during the course of their studies were more likely to
      remain/become insufficiently active (p<0.001). There was no association between
      PAL and access to places for physical activity (p>0.05). CONCLUSION : A tendency
      to an increase in insufficiently active ratio during higher education was
      observed. Policies aimed at training students about health care in universities
      may be useful for increasing physical activity, thus contributing to improve the
      health condition of the students.

PMID- 30183809
TI  - [Risk and physical activity level in adults in a healthy lifestyle program in
      Popayan].
AB  - OBJECTIVE : To characterize risk and physical activity level of the participants
      in a program of healthy habits and lifestyles in the city of Popayan during the
      first semester of 2015. METHODS : Cross-sectional study on the adult population
      participating in a health promotion program developed by the Cauca Governor's
      Office with 500 users. Information was collected through the IPAQ questionnaire
      and risk for physical exercise was classified using the PAR-Q questionnaire.
      RESULTS : The results show a prevalence of 18.3 % for moderate and vigorous
      physical activity. The population group with the highest percentage of physical
      activity was found in young adults (aged 18-35 years), while 64 % of the
      population are at high risk regarding practicing physical exercise. CONCLUSIONS :
      The results obtained show that most of the population is at high risk regarding
      physical activity and also confirm low levels of moderate and vigorous physical
      activity. However, they also show signs of the importance of making evaluations
      prior to developing physical activity programs, such as security measures and
      control and monitoring of health status of the users.

PMID- 30183811
TI  - Enteroparasites in vegetables marketed in an ancient Brazilian city.
AB  - OBJECTIVE : To assess contamination by enteroparasites in raw vegetables consumed
      in the city of Sao Mateus, Espirito Santo, Brazil. MATERIAL AND METHODS : Samples
      of lettuce (Lactuca sativa) and parsley (Petrosolium sativum) were collected from
      six popular establishments, such as supermarkets and street markets. The obtained
      material was analyzed, after washing, by the spontaneous sedimentation method in
      the Clinical Analysis Laboratory of the Federal University of Espirito Santo, Sao
      Mateus Campus. RESULTS : From a total of 120 analyzed samples, 71 (59 %) had one
      or more parasitic contaminants. Lettuce samples had a contamination rate of 78.3
      %, and parsley samples of 40 %. CONCLUSIONS : The results show that the
      vegetables consumed in the city had protozoa, helminths and arthropods, which
      points to the need for implementing hygienic-sanitary measures in production,
      handling and transportation of these vegetables.

PMID- 30183810
TI  - [Profile of body composition in women with class III obesity by multipolar
      bioimpedance method].
AB  - OBJECTIVE : To analyze a body composition profile in women with class III obesity
      using the multipolar bioimpedance method. METHODS : Thirteen sedentary women aged
      between 20 and 40 years were evaluated. RESULTS : The results show that the
      patients had a fat percentage of 51.9+/-1.50 % and lean mass of 48.1+/-1.50 %.
      Regarding fat mass and lean mass per body region, figures of 26.3+/-3.62kg and
      26.2+/-2.91kg in the upper body, 9.1+/-0.06kg and 8.4+/-0.14kg in the lower
      limbs, and 3.3+/-0.02kg and 7.6+/-0.01kg in the upper limbs were obtained.
      Patients had a good symmetry between the left and right sides in both upper and
      lower limbs, besides of a muscular mass of 32.1+/-5.08kg, with a muscular mass
      index of 12.7+/-1.05kg/m2. CONCLUSION : Higher fat accumulation was observed in
      the upper body region, followed by lower and upper limbs. Total muscular mass was
      apparently preserved, although sarcopenic obesity was not verified. Since this is
      a group of people that is still understudied, there is a need for further
      research on genetic and physical profile and caloric expenditure during exercise
      and rest.

PMID- 30183812
TI  - [Assessment of access to the Family Health Strategy from the perspective of users
      in Santo Antonio de Jesus-Bahia, Brazil].
AB  - OBJECTIVE : To assess access to the Family Health Strategy (FHS) in Santo Antonio
      de Jesus - Brazil from the perspective of its users. METHODS : Cross-sectional
      study conducted with a representative sample of users registered by 21 family
      healthcare teams of the municipality, for a total of 430 questionnaires. A family
      based survey was applied between December 2012 and January 2013. Indicators
      considered as the most powerful to evaluate access were selected and,
      subsequently, divided into two dimensions: knowledge and evaluation of the Family
      Health Strategy Program from the perspective of its users. RESULTS : The results
      point to decreasing barriers and increasing access to healthcare services, as
      well as to a greater organization of enrollment in the system. Changes observed
      after the implementation of the FHS in the districts are evident in the overall
      satisfaction with the primary health care service, which legitimizes the
      organization of the health system based on primary comprehensive care.

PMID- 30183813
TI  - [Food (in)security of families living in a city of Paraiba, Brazil].
AB  - OBJECTIVE : To determine the prevalence of food insecurity among families living
      in the municipality of Queimadas and its association with socioeconomic and
      demographic characteristics. METHODS : Cross-sectional study involving 204
      families living in the municipality of Queimadas, state of Paraiba, Brazil,
      attended at public primary health care services and with small children in the
      family core. Food security was assessed by the Brazilian Scale of Food
      Insecurity. The association between food insecurity and socioeconomic and
      demographic characteristics of families was studied using a logistic regression
      model. RESULTS : The application of the scale revealed that 65.4 % of families
      suffered from food insecurity, being 8.4 % mild, 18.5 % moderate and 38.5 %
      severe. High prevalences of food insecurity were found in families not receiving
      social program and in precarious conditions related to sanitation (no toilet
      inside houses, without toilet flushing, consumption of untreated water, open
      sewage). CONCLUSIONS : The present study shows that more than half of the
      families with young children living in the city of Queimadas, served in public
      primary health services, live in a state of food insecurity and that
      socioeconomic characteristics are determinant of this state.

PMID- 30183814
TI  - [Cost-effectiveness of risk stratification tests for the treatment of acute
      myeloid leukemia in pediatric patients].
AB  - OBJECTIVE : To estimate the cost-effectiveness of risk-stratification tests for
      the treatment of acute myeloid leukemia (AML) in pediatric patients. METHODS : A
      decision-tree model was built using Life Years Gained as a measure of
      effectiveness. Costs were estimated considering the perspective of the Colombian
      health system. Stratification costs included treatment costs based on said
      stratification. Drug prices were taken from SISMED (Drug Price Information
      System) 2008 and the monetary value of the procedures was extracted from the ISS
      2001 rate manual, plus 30%. All costs were expressed in Colombian pesos for 2010
      and the gross domestic product per capita of the same year was used as a cost
      effective threshold. Univariate and probabilistic sensitivity analyzes were
      performed. RESULTS : Risk stratification tests have an incremental cost
      effectiveness ratio of COP 8,559,944. These results are sensitive to changes in
      probabilities of relapse, transplant survival and side effects. CONCLUSION : Risk
      stratification tests for AML treatment in pediatric patients are cost-effective
      in the context of the Colombian health care system.

PMID- 30183815
TI  - [Peace experiences in occupational therapy: contributions from Colombian
      regions].
AB  - OBJECTIVE : To identify and characterize professional experiences in occupational
      therapy in different regions of Colombia regarding the overcoming of the armed
      conflict. METHODS : Cross-sectional, descriptive study in which the digital
      version of the Survey on professional experiences in the Colombian armed conflict
      was applied using Type-form. 34 occupational therapists responded the survey. The
      sample filled the corresponding informed consent to participate in the study.
      RESULTS : The overall balance shows that experiences are mostly concentrated in
      the Andean region and cover 18 departments of the country, while a representative
      percentage are observed in works with indigenous communities. Intervention has
      targeted mainly adults and victims and people with disabilities, although
      greatest emphasis is on communities. Therapists are involved mainly as executors
      and university professors. Finally, there is concern about the presence of
      illegal armed actors and the reality of an overwhelming problem. Achievements
      include the impact of the intervention and the capitalized professional and
      personal learning. CONCLUSIONS : A territorial approach requires greater presence
      in the regions and cultural sensitivity. Strengthening the work carried out with
      the population that was linked to illegal armed groups through occupational
      resignification processes allow to make progress in the expected economic and
      social reincorporation.

PMID- 30183816
TI  - [Foodborne disease outbreaks studied by molecular techniques].
AB  - OBJECTIVE : To apply a multiplex real-time polymerase chain reaction (PCR)
      technique to detect Salmonella spp., Listeria monocytogenes, and Yersinia
      enterocolitica as a diagnostic support tool for the surveillance of foodborne
      disease outbreaks. MATERIALS AND METHODS : Molecular methodology was applied on
      clinical samples taken from individuals who were associated with foodborne
      disease outbreaks in two departments of Colombia. The results were compared with
      the data obtained by conventional culture methodology. In addition, the clonal
      relation of the isolations was evaluated using the Pulsed Field Gel
      Electrophoresis (PFGE) technique. RESULTS : 123 cases of foodborne disease were
      determined, of which 45 biological samples were confirmed by laboratory and 88 by
      epidemiological link. The molecular methodology detected 35/45 positive samples
      versus 17/45 positive samples detected by conventional methodology. PFGE
      demonstrated a clonal relation during each outbreak. CONCLUSION : The results of
      the study demonstrate the applicability of the molecular technique as a useful
      diagnostic support tool to characterize foodborne disease outbreaks, allowing a
      timely and reliable response.

PMID- 30183817
TI  - [Health literacy and associated factors in patients attending the Outpatient
      Internal Medicine Service of a national hospital of Lima, Peru].
AB  - OBJECTIVE : To determine health literacy in patients attending the Outpatient
      Internal Medicine Service of a national hospital of Lima, Peru, in March 2014 in
      order to establish factors associated with inadequate health literacy. MATERIALS
      AND METHODS : Descriptive study. The Short Assessment of Health Literacy for
      Spanish Adults (SAHLSA-50) was used after partial cultural validation. Expert
      opinion and measurement of the correlation coefficient were considered.
      Subsequently, the test was applied in a sample of 363 patients selected by simple
      systematic random sampling. RESULTS : For partial cultural validation, 17 items
      of the original test were modified and a Pearson correlation coefficient of
      r=0.81 was obtained. After cultural validation, the test was applied, finding
      that 73.3 % were women, 14.0 % were seniors, and 52.6 % completed high school.
      Furthermore, 35.3 % were affiliated to health insurance subsidized by the
      government (Comprehensive Health Insurance or SIS by its acronym in Spanish).
      15.20 % did not use any health service during the past year and 34.4 % had
      inadequate health literacy. Variables such as senior age, poor education, SIS
      insurance and fewer visits to health services within the past year have a
      significant association with inadequate levels of health literacy (p<0.05).
      CONCLUSIONS : One third of patients attending the Outpatient Internal Medicine
      Service of the Hospital Nacional Arzobispo Loayza had inadequate health literacy.
      Variables such as senior age, poor education, SIS insurance and fewer visits to
      health services within the past year have a significant association with
      inadequate levels of health literacy.

PMID- 30183818
TI  - Anchoring bias in face-to-face Time-Trade-Off valuations of health states.
AB  - OBJECTIVE : To test whether anchoring (a cognitive bias) occurs during face-to
      face interviews to value health states by Time-Trade-Off. METHODS : 147 Colombian
      subjects (111 males, 36 females) valued five EQ-5D health states better than
      death during a face-to-face interview. Subjects were randomly assigned to two
      different starting points. RESULTS : Shapiro-Wilk test discarded normality, while
      non-parametric tests, including Kolmogorov-Smirnov and Wilcoxon-Mann-Whitney,
      showed that anchoring was significant in four out of five health states. A higher
      starting point increased the elicited value by 15 %-188 %. The size of the
      anchoring effect was not uniform among health states. CONCLUSION : Anchoring
      effects may bias face-to-face Time Trade-Off valuations. The size of the
      anchoring effect is relevant enough for health policy.

PMID- 30183819
TI  - Intestinal parasites among employees of restaurants and cafeterias in a city of
      Brazil.
AB  - OBJECTIVE : To investigate the frequency of intestinal parasites in employees of
      restaurants and cafeterias located in the Commercial Center of Sao Mateus,
      Espirito Santo, one of the oldest cities of Brazil. MATERIAL AND METHODS :
      Between August 2013 and February 2014, 42 fecal samples were collected and
      analyzed by spontaneous sedimentation method in the Clinical Analysis Laboratory
      of the Federal University of Espirito Santo, Sao Mateus Campus. RESULTS : The
      results were positive in 19 % of the samples. The commensal Entamoeba coli (75 %)
      was the most common followed by Entamoeba histolytica/dispar (37.5 %) and Giardia
      lamblia (12.5 %). CONCLUSIONS : Implementing health education measures in the
      city of Sao Mateus is suggested by providing permanent health education, as well
      as conducting parasitological examinations. Such actions will contribute to the
      improvement of health conditions of the population.

PMID- 30183820
TI  - Business performance management in university hospitals: a diagnosis in Brazilian
      institutions.
AB  - OBJECTIVES : To investigate whether business performance management practices are
      used by Brazilian federal university hospitals, and if so, to determine which
      practices are used and explore characteristics that may be related to their
      adoption. METHOD : Descriptive ex post facto research on the effects of the
      studied variables in relation to the technical procedures. Secondary data and
      survey resources were used. RESULTS : Four hospitals use practices to assess
      business performance. Three of them stated that they use two different types of
      practices and that 75 % of university hospitals with at least one business
      performance management practice also have a strategic plan that includes vision,
      mission, objectives and long-term operational plans. Among the hospitals that do
      not use business performance management practices, 55.6 % claim to have strategic
      planning composed at least of mission, vision and long-term objectives. However,
      they stated that the entity has no plans to adopt any method. CONCLUSIONS : This
      diagnosis intends to draw the attention of managers and other actors in the field
      of public health on the possibilities offered by performance evaluation systems
      to promote administrative improvements in a complex internal scenario with a need
      for rationalization of hospital costs in order to direct these institutions
      towards achieving their social mission.

PMID- 30183821
TI  - [International collaborative process for adaptation of PCAT questionnaires to the
      Colombian context].
AB  - OBJECTIVE : To obtain versions adapted to the Colombian context of the Primary
      Care Assessment Tools Child Edition and Adult Edition questionnaires (PCAT-CE and
      PCAT-AE, respectively) to assess the functions of primary care with equivalence
      to their original versions. METHODS : Transcultural adaptation process based on
      the adapted versions in Spanish validated in Argentina, Uruguay and Spain, in
      agreement with the Ibero-American Collaboration IA-PCAT. RESULTS : Eighteen out
      of 99 PCAT-CE items and 31 out of 112 PCAT-AE items were suitable for Colombia
      according to the Latin American versions. Of them, 76 and 73, respectively,
      required minimal idiomatic changes, 2 and 4 required major changes, and 1 and 4
      items were removed. Interviews confirmed understanding and allowed improvements.
      CONCLUSIONS : Versions tailored to the Colombian health system were obtained. The
      methodology used capitalized on the results of other countries and can contribute
      to achieving greater equivalence between instruments from different countries.

PMID- 30183822
TI  - [Implementation of a policy for early childhood care in the Chilean context: a
      view from health to "Chile Crece Contigo"].
AB  - In the field of childhood care, Chile has a long history of interventions which
      have pointed to reduce infant mortality, most of them with a strong biomedical
      approach. These interventions have attempted to respond to the demands of the
      period when they were established, reflecting the evolution of social and health
      history of the Chilean State and achieving good results during the past century.
      In this context the Chile Crece Contigo (Chile grows with you) public policy was
      created to bet on a biopsychosocial approach to early childhood through a serie
      of actions aimed at protecting and accompanying children throughout their
      development, with special emphasis on support to the most vulnerable families.
      This essay presents the background of the public policy for early childhood
      protection in the Chilean context, from a health perspective, and also presents
      briefly some important aspects of the implementation process of one of its most
      significant policies.

PMID- 30183823
TI  - [Perception of adolescent pregnancy in the Department of North Santander,
      Colombia].
AB  - OBJETIVE : Analyze the perception of adolescent pregnancy in the Department of
      North Santander. METHOD : A descriptive cross-sectional study was conducted with
      406 adolescent mothers between 10 and 19 years old in 6 sub-regions of the
      department. We used a structured survey and the Statistical Package for the
      Social Sciences (SPSS; Version No. 23) was employed for the data tabulation.
      RESULTS : 69 % of adolescents believe that unplanned pregnancy is associated with
      the lack of sexual education. 66 % say that it is preventable with the use of
      contraceptive methods. It is known that unwanted pregnancies are the main cause
      of school dropouts for 62 % of adolescents. DISCUSSION: Ensuring greater access
      to sex education and facilitating the free and easy access to contraception can
      reduce the problem of teen pregnancy.

PMID- 30183824
TI  - [Evaluation of the barriers to the practice of physical and sport activities in
      Spanish adolescents].
AB  - OBJECTIVE : To identify which factors adolescents perceive as preventing them
      from undertaking physical activity in their spare time. METHODS : A cross
      sectional descriptive and quantitative methodology was followed. The sample
      consisted of a total of 324 students (54.3 % girls and 45.7 % boys) enrolled in
      Mandatory Secondary Education with a mean age of 14.01+/-1.35 years old. The data
      was selected using the Short Scale of Perceived Barriers for the Physical
      Activity in Adolescents. The analyzed variables include self-perception of motor
      competence, motivation or interest, social support, and incompatibility with
      other activities. These barriers are analyzed in relation to gender and grade
      level. RESULTS : There are significant differences between self-perception of
      motor competence and motivation in relation to gender. Furthermore, there are
      significant differences in all variables except in the one of incompatibility
      with other activities in relation to grade level. CONCLUSION : Girls have a worse
      self-perception of motor competence and motivation to practice physical activity.
      However, the oldest students (15-16 years old) present better self-perception of
      motor competence, motivation and social support.

PMID- 30183825
TI  - Clinical markers associated with acute laboratory-confirmed Dengue infection:
      results of a national epidemiological surveillance system.
AB  - OBJECTIVE : To evaluate the association of several clinical markers with acute
      laboratory-positive Dengue Virus infection. METHODS : A hospital-based case
      control study was conducted in the state of Colima, Mexico, by using information
      from the National System of Epidemiological Surveillance (Sistema Nacional de
      Vigilancia Epidemiologica [SINAVE]) for Dengue. Data from 2 732 cases and 2 775
      frequency-matched controls were analyzed. Odds Ratio (OR) and the 95 % Confidence
      Interval (CI), estimated by means of logistic regression models, were used.
      RESULTS : The presence of skin rash (OR=1,7; 95 % CI 1,5-2,1), persisting
      vomiting (OR=1,8; 95 % CI 1,5-2,3) and increased capillary fragility (petechiae,
      ecchymosis, hematoma or positive tourniquet test; OR=1,8; 95 % CI 1,2-2,6) were
      associated with laboratory-positive infection. CONCLUSIONS : Three clinical
      markers were significantly associated with an increased risk of acute laboratory
      confirmed dengue infection. These findings would support accurate and timely
      diagnosis of dengue in laboratory-limited settings.

PMID- 30183826
TI  - [Cardiovascular risk factors in a coffee-growing region of the Department of
      Caldas].
AB  - OBJECTIVES : To determine the cardiovascular risk factors in a coffee population
      of the department of Caldas. MATERIALS AND METHODS : A Cross-sectional study was
      carried out in 2015 to 964 coffee growers affiliated to la Cooperativa de
      Caficultores de Manizales in six sites located in the center and east of the
      department. After the survey, anthropometric measures and biochemical tests were
      performed. The results were analyzed in the Statistical Package for the Social
      Sciences (SPSS). RESULTS : The incidences in the study were: Male gender 78 %,
      smoking prevalence 27.2 %, background information of family members deceased
      before 55 years old by coronary etiology 24 %, arterial hypertension 14 %,
      hypercholesterolemia 56.58 %; the circumference of the waist for men 90.7 cm and
      for women 88.1; the body mass index average for the population was 24.7 kg/m2.
      CONCLUSIONS : Hypercholesterolemia was the common and most predisposing
      cardiovascular risk factor for the development of cardiovascular disease in this
      population; the early detection of risk factors allows developing promotion and
      preventing strategies in order to reduce their morbidity, mortality, disability
      and costs associated with cardiovascular disease.

PMID- 30183827
TI  - [Metabolic syndrome and physical activity in elderly people from the Ecuadorian
      highlands].
AB  - OBJECTIVE : Determine the prevalence of the metabolic syndrome, the level of
      physical activity and the association with these factors in the elderly from the
      Ecuadorian highlands. METHODS : Cross-sectional study that evaluated 387 older
      adults from Cuenca-Ecuador, who wished to participate and signed the informed
      consent. The diagnosis of metabolic syndrome was made using the criteria of the
      National Program of Education on Cholesterol and the Adult Treatment Panel III,
      for the value of Abdominal Circumference the criteria used for the Asian
      population was considered. The level of physical activity was evaluated by the
      short version of the International Physical Activity Questionnaire. The groups
      with and without metabolic syndrome were compared using the chi-square test and
      student's t-test. The analysis of variance was used to evaluate the association
      between the components of the metabolic syndrome and the level of physical
      activity. RESULTS : The prevalence of metabolic syndrome was high (59.9 %), as
      well as the high level of physical activity (45 %), however, there was no
      significant association between the metabolic syndrome and physical activity
      level. CONCLUSIONS : Older adults diagnosed with metabolic syndrome presented the
      same level of physical activity as individuals without this diagnosis. It is
      necessary to confirm the present findings using direct measurement instruments of
      physical activity.

PMID- 30183828
TI  - [Virtual objects for self-regulated learning of occupational therapy students].
AB  - OBJECTIVE : To identify the relationship between the characteristics of students,
      their learning environment, their occupation, and the virtual objects for self
      regulated learning. In addition, to establish connections with participant's
      observation. Important aspects for the training of health professionals. METHODS
      : A qualitative study was applied to students who participated in the Education
      and Occupational Therapy subject. Two tools were used: virtual Objects
      Questionnaire for the educational field learning and Participant Observation. The
      first instrument was piloted and reviewed by experts. RESULTS : The study
      reported similar demographic data and background of similar education in relation
      to: origin, access to the computer and exclusivity to study; as well as the
      development of secondary education studies in Bogota and in private institutions.
      In the learning environments, there is a tendency to show that they agree with
      the program of the subject in fulfillment of explicit objectives chosen for the
      study in 75 % and implicit in 60 %. With regards to the occupation, it was found
      that the virtual object allowed to deepen on the subject that the students
      developed and put into practice previous knowledge on communication technologies.
      The Participant Observation tool found particularities in the elements of
      motivation, efficacy and self-regulated learning. CONCLUSIONS : The
      implementation of the Virtual Learning Objects favor the students' motivation,
      self-regulated learning and their appropriation of concepts and knowledge related
      to the subject; therefore, it is proposed as a learning strategy.

PMID- 30183829
TI  - [Identification of knowledge about the quality of mortality information in
      Bogota].
AB  - OBJECTIVE : Identify the workers knowledge involved in the production and usage,
      about the quality of mortality information in Bogota during 2006. METHODS : We
      conducted a descriptive study using a self-administered and semi-structured
      questionnaire in 130 functionaries who participated in the mortality data
      production and use. The instruments inquired into the reliability,
      characteristics, qualification, reasons for that qualification and improvement
      proposals. We calculated frequencies and percentage distributions. RESULTS : 76.2
      % of respondents identified coverage and content as the aspects that best
      indicated reliability of mortality information. The main quality characteristics
      of the information recognized were veracity, 80.8 %; completeness, 76.2 %;
      accuracy, 75.4 %; opportunity, 74.6 %; and validity, 73.8 %. 55.4 % of
      participants rated the quality as fair and 6.2 % as poor. Some of the proposals
      for the quality improvement were awareness, training and evaluation processes.
      CONCLUSIONS : The findings suggest that there is still a lack of knowledge about
      the quality of mortality information in people involved in its production and
      use. It is necessary to correct this lack of knowledge by implementing the
      proposals to improve the quality of mortality data made by respondents. It is
      recommended that the various proposals that were exposed are monitored and
      evaluated to determine the impact they produce.

PMID- 30183830
TI  - [Work and health: The constitutional court and the protection of constitutional
      rights in work-related accidents and illnesses].
AB  - OBJECTIVE : To describe the way in which the Constitutional Court of Colombia has
      interpreted the use of the writ for the protection of constitutional rights in
      work-related illnesses. The paper explains in which cases the court has defended
      the use of this action and the key judicial precedents on the subject. METHOD :
      Analysis of a representative sample of the decisions of the Constitutional Court
      regarding writs for the protection of constitutional rights in work-related
      illnesses between 1992 and 2014. We coded 58 rulings, providing descriptive
      statistics and analyzing the main judicial precedents. RESULTS : The Court has
      assumed a protectionist position in support of workers. In 79.3 % of the cases,
      the Court revoked the decisions of lower courts and granted the action to
      employees. The Court has defended that employers cannot dismiss workers who
      suffered from a labor accident or illness without approval from the labor office;
      these workers have to be reincorporated and relocated, if needed, in a new
      working place. The Court has also stated that workers do not have to bear the
      uncertainty of not knowing which entity should cover their health and economic
      costs during recovery; health promoting companies (EPS, the Spanish acronym) or
      occupational risk managers (ARL, the Spanish acronym) should cover these costs
      while courts have a definite ruling. DISCUSSION : The institutional structure of
      labor risks in which EPS takes-over sicknesses and accidents from a common
      origin, and ARL the ones from a labor origin, incentivize EPS and ARL rejection
      of the services and, therefore, the use of the legal action of writ for the
      protection of constitutional rights. In spite of the clarity of judicial
      precedents, the same judicial controversies keep re-emerging, and lower courts
      continue to fail to comply with the precedents established by the Court.

PMID- 30183831
TI  - [Perceptions about their own old age from the perspective of a group of
      epidemiologists in training].
AB  - OBJECTIVE : Exploring, from the perspective of a group of epidemiologists in
      training, the perceptions about their own old age. MATERIAL AND METHODS :
      Exploratory, qualitative-descriptive study, in which ethnographic tools were
      applied: observation, field diary and group interview (GF). RESULTADOS : Explored
      from the perspective of a group of epidemiologists in training. The group agreed
      that to plan to reach a functional and decent old is important, despite the
      current unfavorable and adverse conditions, recognizing that not all will reach
      there, and it is less common for young people to think and plan their own old
      age, and even less work with and for the elderly. The meaning of aging most often
      mentioned by the group contain the word "phase", in which concept and care
      reflect the high standards desired individually. It became clear, that nursing
      homes for old age people are necessary, but the services provided are
      differentiated since "the economy determines the care for the elderly".
      CONCLUSION : Reflecting on the perception of old age itself, for the group of
      epidemiologists in training, helped visualize their concerns, fears,
      expectations, and to reflect on their responsibilities and possibilities in
      providing scientific evidence to plan and make sound decisions for a dignified
      old age and aging of the population from Narino.

PMID- 30183832
TI  - [Public policies of zoonoses in Colombia, 1975-2014. An approach from Political
      Science and Public Health].
AB  - OBJECTIVE : To analyze public policies regarding zoonoses in Colombia, in terms
      of responsiveness, decision-making, processes and results, approaching their
      impact in the period between 1975 and 2014. METHODS : An analysis and assessment
      of public policies were carried out using a mixed design. Some zoonoses were
      selected based on their importance for public health, epidemiology, policy and
      availability of consecutive information. Secondary documentary sources and
      primary sources were used through an annotated survey. An interpretive,
      historical and structural framework was built from an economic, epidemiological
      and political point of view. For policy analysis, the sequential approach was
      used and, in a complementary manner, the institutional development approach. A
      trend analysis of selected zoonoses was carried out. RESULTS : The interpretive
      framework addressed the macro context and the key processes in two periods: 1975
      1990 and 1990-2014. The analysis of public policies in zoonoses was conducted
      according to their decision level and the vertical and horizontal relationships
      between them. A trend analysis of zoonoses in the long term, as well as an
      assessment of the impact of the policies, was obtained. CONCLUSIONS : Policy
      diversification and instrumental depth suggest that they have approached the
      understanding and management capacity of the complex problems of zoonoses.
      However, the trend analysis suggests that the impact of public policies on
      zoonoses is still limited.

PMID- 30183833
TI  - Identification of enteroparasites in recreation areas of elementary schools in
      Northern Espirito Santo, Brazil.
AB  - OBJECTIVE : Since sand is an important child means of contagion by
      enteroparasites, this study aimed to conduct a parasitological evaluation in
      recreation areas of elementary schools and early childhood education centers, in
      Sao Mateus-ES. MATERIAL AND METHODS : Sand samples were collected in seven
      municipal elementary schools and in a municipal kindergarten and nursery center.
      For the recovery of helminth eggs and protozoan cysts, flotation and spontaneous
      sedimentation techniques were used. RESULTS : It was found that 77 % of the
      analyzed institutions were positive for helminth eggs and larvae. Among the eggs
      and larvae identified, the main were Ascaris lumbricoides and Toxocara canis.
      Pearson's chi-square test identified the best results when using the spontaneous
      sedimentation method. CONCLUSIONS : Considering that individuals, especially
      children living in poor sanitation conditions, are more prone to enteroparasites,
      studies point to the need of the application of preventive and health education
      measures for the population enrolled in municipal schools in Sao Mateus.

PMID- 30183834
TI  - In vitro antifungal susceptibility of clinical isolates of Fusarium from
      Colombia.
AB  - OBJECTIVE : The aim of the present study was to evaluate the antifungal
      susceptibilities of isolates of Fusarium to amphotericin B, itraconazole and
      voriconazole. METHODS : The susceptibility of 44 isolates of Fusarium was tested
      by the E-test methodology. RESULTS : All the isolates were resistant to
      itraconazole, and 89 % and 54,5 % were resistant to amphotericin B and
      voriconazole, respectively. DISCUSSION : The results confirm the high level of
      resistance reported, regardless of the species or the strain of Fusarium
      involved. The high MICs level observed are worrying and suggest that new drugs
      are needed.

PMID- 30183835
TI  - [Description of bacterial microbiota in biosolids generated in the San Fernando
      wastewater treatment plant. Itagui, Colombia].
AB  - OBJECTIVE : To describe bacterial microbiota in the biosolids generated in one of
      the largest wastewater treatment plants of Colombia. MATERIALS AND METHODS :
      Using NGS technology, 16S rRNA Gene Amplicon libraries were amplified and
      sequenced. The Roche 454 FLX Titanium platform was used, while the V1-V3 and V6
      V9 hypervariable regions were amplified and analyzed independently. Amplicon
      processing and bacterial classification were performed using the AmpliconNoise
      pipeline and the RDP Classifier tool. RESULTS : The analysis showed that the most
      dominant Phyla in the biosolids were Chlo-roflexi, Proteobacteria, Bacteroidetes,
      Actinobacteria and Firmicutes. The most dominant genera were Pseudomonas,
      Dysgonomonas and Proteiniphilum; however, the dominant group according in the V1
      V3 variable region was Anaerolineaceae, which does not conform to the species
      described for this family. Pathogenic bacteria such as Salmonella and E.
      coli/Shigella were not detected in the studied biosolid sample. CONCLUSIONS : In
      the biosolids samples analyzed, environmental bacteria involved in organic matter
      stabilization processes during secondary biological treatments and anaerobic
      digestion were predominant. One of the dominant species in this sludge is a novel
      species of the Anaerolineaceae group. At the time of the study, it was found that
      the anaerobic digester system was able to maintain pathogenic bacteria at very
      low concentrations.

PMID- 30183836
TI  - [Resistance to polychemotherapy in patients with Hansen's disease].
AB  - This paper describes a case report of a patient from the Sanatorio Agua de Dios
      Cundinamarca diagnosed with histioid lepromatous leprosy with suspected
      resistance to polychemotherapy (PQT), making evident the importance of clinical
      criteria for initiating an alternative therapy given the limitations of
      paraclinical examinations. Resistance should be suspected and diagnosed early to
      prevent the progression of the disease; clinical and paraclinical criteria help
      to confirm diagnosis. In bacteriological studies, the Colombian semiquantitative
      scale should be replaced by the Ridley-Jopling logarithmic scale.
      Histopathological studies are conducted on all patients with Hansen's disease.
      Research on resistance is being implemented in the country, but its access limits
      the opportunity for support in therapy initiation.

PMID- 30183837
TI  - [Prevalence and associated factors with sexual violence against women: systematic
      review].
AB  - This review aims to identify in the literature the prevalence and factors
      associated with Sexual Violence (SV) against adolescents and adult women. It were
      reviewed the population-based study, published between 2011 and 2016, in English,
      Portuguese and Spanish, in Pubmed / Medline, Lilacs and SciELO databases. The
      studies were analyzed and described, detailing their characteristics and
      information on prevalence and factors associated with SV. Of the 3,002 articles
      found, according to the eligibility criteria, 15 studies were objects of this
      review. Most studies focus on Asia and Africa, which also have the highest
      prevalence of SV. The predominantly investigated age group was 15-49 years. There
      was a great variation in the prevalence of SV among the countries, when SV was
      analyzed by intimate partner, it varied from 1 % in Germany in the current
      relationship to 92 % Zimbabwe. In relation to the associated factors, low
      educational level, young age, mental health conditions and sexual and
      reproductive health, as well as the use of alcohol and other drugs are
      highlighted. The review highlights the need to deepen studies on sexual violence
      to contribute to public policies, to combat violence against women and to gender
      equity.

PMID- 30183838
TI  - [Ethical considerations for health research regarding Colombian indigenous
      peoples].
AB  - Health research can produce valuable insights to guide interventions offered to
      individuals and human groups. However, it requires specific precautions to
      protect potentially vulnerable subjects, such as indigenous populations. It has
      been recognized that there has been unethical conduct in research -from the
      international authorities responsible for outlining ethical standards for
      research projects- with regards to indigenous peoples. This article presents and
      discusses national and international guidelines to regulate research involving
      indigenous peoples. In summary, respect for the autonomy and for the own
      knowledge are rights that must be met to carry out scientific research with
      indigenous peoples. In addition to the informed consent, the process of
      consultation and agreement allows adequate contextualization in relation to the
      problems, needs, and benefits of research in these populations.

PMID- 30183839
TI  - [Challenges of menstruation in girls and adolescents from rural communities of
      the Colombian Pacific].
AB  - OBJECTIVE : To understand the challenges and experiences related to menstruation
      in girls and adolescents from rural communities of the Colombian Pacific. METHOD
      : Mixed research, mainly qualitative and quantitative to a lesser extent, which
      combined ecological, differential and intercultural approaches, as well as gender
      perspective. The participants were girls and adolescents, young people,
      teachers/principals of educational institutions, mothers and parents in general,
      as well as institutional officers from the Municipal Health and Education
      Secretariats, the Ministries of Health and Education, and the Vice-ministry of
      Water and Sanitation. Focus groups, in-depth interviews, surveys and the
      educational institutions were carried out in schools. The research was conducted
      in the municipalities of Bagado (Choco), Ipiales (Narino) and Santander de
      Quilichao (Cauca). RESULTS : This study showed that insufficient information at
      the time of menarche, pain, poor access to restrooms, water and absorbent
      materials, as well as existing prejudices, cause menstruation to be experienced
      with pain and concealment. All these aspects are correlated with absenteeism in
      school and the strengthening of prejudices around "being a woman". Inequality in
      girls and adolescents, derived from constructs around menstruation, goes
      unnoticed by schools, families, entities and officers in charge of public policy
      management. CONCLUSIONS : Social and cultural constructs around menstruation in
      the municipalities studied lead to its configuration as a negative experience,
      which generates and reinforces taboos that materialize in inequity, stigma and
      discrimination against girls. In this context, community work and the design of
      public policies and actions are fundamental to promote gender equity.

PMID- 30183840
TI  - [Trajectory of a young female inmate in relation to drug use and gender-based
      constraints].
AB  - This text aims to analyze socio-cultural aspects in relation to the trajectory of
      habitual consumption of psychoactive substances of a young inmate. The young
      woman was in a detention center for minors in Medellin, Colombia, where
      interviews were conducted and participant observation was carried out. From
      there, the importance of aspects related to gender as a protective and risk
      elements was evident. Finally, this study presents some elements related to the
      detoxification process while she was following her sanction in internment.

PMID- 30183841
TI  - [Sexual and reproductive health of adolescents in Chile: the role of sexual
      education].
AB  - OBJECTIVE : To explore the perceptions of adolescents regarding sex education in
      the Metropolitan Region of Chile, and the role of the health and education
      sectors in this matter. METHODS : Qualitative ethnographic study, whose fieldwork
      was carried out in five municipalities of the Metropolitan Region of Chile. In
      each municipality a Friendly Space for adolescent healthcare was studied. Semi
      structured interviews (N=38), discussion groups (N=5) and participant observation
      techniques were used. RESULTS : A negative perception among adolescents was
      identified regarding the sex education they receive.They express that there is a
      need for information on sexual and reproductive health, which addresses in depth
      the biological, emotional and affective dimensions of sexuality, overcoming
      conservative and risk-based approaches to sexuality. Innovative health strategies
      focused on schools were identified, where the health and education sectors work
      collaboratively on sex education. DISCUSSION : When the health and education
      sectors work in a collaborative and coordinated manner, a better response to the
      needs of adolescents can be achieved in terms of information and sex education.
      Although this intersectoral work constitutes a progress, the challenge of
      incorporating the voices of adolescents and their communities remains to be
      addressed to plan sex education programs and policies based on their life
      experiences, thus advancing towards sexual and reproductive rights for this
      group.

PMID- 30183842
TI  - [Suffering from depression as a Mexican immigrant woman in New York City].
AB  - OBJECTIVE : To describe the living conditions of migrant women and their
      correlation with the development of depression at the place of destination.
      METHODS : Ethnographic work developed in the city of New York, specifically in
      the Queens borough. Six first-generation immigrant women, part of the migratory
      circuit of Puebla-Nueva York, were included in this study. In-depth interviews,
      development of migratory trajectories and therapeutic itineraries were applied.
      Finally, interviews were conducted with relatives of the main informants to
      control biases or omissions. RESULTS : The relationship between violence and
      women's mental health was identified. Violence occurred in various stages of
      their lives and spaces in which they lived and developed their daily living. The
      violence was accentuated by the hierarchical relationships in the domestic group
      and work space. Furthermore, economic crisis and family arrangements were
      detrimental factors. The family arrangements to get ahead and provide continuity
      to the family model despite migration were also related to the stress they lived
      in their homes. DISCUSSION : The living conditions of women and their influence
      on the development of mental illnesses were discussed regarding other studies
      that, from a public health perspective, have addressed the mental health and
      migration issues through acculturation and assimilation concepts.

PMID- 30183843
TI  - Sampling plan in health surveys, city of Sao Paulo, Brazil, 2015.
AB  - OBJECTIVE: To evaluate the sampling plan of the Health Survey of the City of Sao
      Paulo (ISA-Capital 2015) regarding the accuracy of estimates and the conformation
      of domains of study by the Health Coordinations of the city of Sao Paulo, Brazil.
      METHODS: We have described the population, domains of study, and sampling
      procedures, including stratification, calculation of sample size, and random
      selection of sample units, of the Health Survey of the City of Sao Paulo, 2015.
      The estimates of proportions were analyzed in relation to precision using the
      coefficient of variation and the design effect. We considered suitable the
      coefficients below 30% at the regional level and 20% at the city level and the
      estimates of the design effect below 1.5. We considered suitable the strategy of
      establishing the Health Coordinations as domains after verifying that, within the
      coordinations, the estimates of proportions for the age and sex groups had the
      minimum acceptable precision. The estimated parameters were related to the
      subjects of use of services, morbidity, and self-assessment of health. RESULTS: A
      total of 150 census tracts were randomly selected, 30 in each Health
      Coordination, 5,469 households were randomly selected and visited, and 4,043
      interviews were conducted. Of the 115 estimates made for the domains of study,
      97.4% presented coefficients of variation below 30%, and 82.6% were below 20%. Of
      the 24 estimates made for the total of the city, 23 presented coefficient of
      variation below 20%. More than two-thirds of the estimates of the design effect
      were below 1.5, which was estimated in the sample size calculation, and the
      design effect was below 2.0 for 88%. CONCLUSIONS: The ISA-Capital 2015 sample
      generated estimates at the predicted levels of precision at both the city and
      regional levels. The decision to establish the regional health coordinations of
      the city of Sao Paulo as domains of study was adequate.

PMID- 30183844
TI  - Sleep duration, health status, and subjective well-being: a population-based
      study.
AB  - OBJECTIVE: To evaluate, in a population-based approach, the association of
      extreme sleep duration with sociodemographic factors, health, and well-being.
      METHODS: We analyzed the data from the 2014/2015 Health Survey in the city of
      Campinas, State of Sao Paulo, Brazil (ISACamp), performed with 1,969 individuals
      (>= 20 years old). Associations between the independent variable and short (<= 6
      hours) and long (>= 9 hours) sleep were determined using the Rao-Scott chi-square
      test. The analyses were adjusted with multinomial logistic regression models.
      RESULTS: Men, individuals aged 40 to 59, those with higher schooling, those who
      have one (OR = 1.47, 95%CI 1.02-2.12), two (OR = 1.73, 95%CI 1.07-2.80), or three
      or more (OR = 1.62, 95%CI 1.16-2.28) chronic diseases, and those with three or
      more health problems (OR = 1.96, 95%CI 1.22-3.17) were more likely to have a
      short sleep. The chance of long sleep was higher in widowers and lower in those
      who have more years of schooling, with higher income, worked, lived with more
      residents at home, and reported three or more diseases (OR = 0.68, 95%CI 0.48
      0.97) and health problems. The chance of either short (OR = 2.41, 95%CI 1.51
      3.87) or long sleep (OR = 2.07, 95%CI 1.23-3.48) was higher in unhappy
      individuals. CONCLUSIONS: These findings highlight the higher chance of short
      sleep duration among men, among persons in productive age, and among those with a
      higher level of schooling in a Brazilian city. The association of short sleep
      with comorbidities and the association of happiness with extremes of sleep
      duration were also important results to understand the relation of sleep duration
      with health and well-being.

PMID- 30183846
TI  - [Safety and environmental risks of coal fired boilers in small and medium-sized
      enterprises "SMEs", located in Itagui town, Antioquia].
AB  - OBJECTIVE : To describe the environmental and safety risks present in coal fired
      boilers in small and medium-sized enterprises, located in Itagui town. METHOD :
      Cross sectional descriptive study: An appropriate sample of 8 boilers with its
      corresponding operators was selected. The description of the boilers was carried
      out through the implementation of four instruments to evaluate and assess
      security risks; Its level of safety, the environmental risks and the
      environmental impacts. RESULTS : The security risk outcome showed that 62 % of
      the boilers presented an unacceptable level of risk. The safety level outcome
      showed that 62 % of boilers obtained a poor rating. The environmental risk
      outcome indicated that 100 % of the boilers had a high level of environmental
      impact and a medium level of impact for operators. Regarding the environmental
      impact assessment, 100 % of the boilers under study showed a high level of impact
      on the air component and medium level of impact on water and soil components.
      CONCLUSIONS : Due to the low level of safety and the high level of environmental
      risk found in the boilers under study; SMEs should be aware of the current risks
      in order to reduce the exposure of the operators to health danger and the
      environme tal impacts as well. Moreover, it is needed to implement management
      measures aimed to prevent and control the risks described.

PMID- 30183845
TI  - Area deprivation measures used in Brazil: a scoping review.
AB  - OBJECTIVE: To describe and assess currently used area-based measures of
      deprivation in Brazil for health research, to the purpose of informing the
      development of a future small area deprivation index. METHODS: We searched five
      electronic databases and seven websites of Brazilian research institutions and
      governmental agencies. Inclusion criteria were: studies proposing measures of
      deprivation for small areas (i.e., finer geography than country-level) in Brazil,
      published in English, Portuguese or Spanish. After data-extraction, results were
      tabulated according to the area level the deprivation measure was created for and
      to the dimensions of deprivation or poverty included in the measures. A narrative
      synthesis approach was used to summarize the measures available, highlighting
      their utility for public health research. RESULTS: A total of 7,199 records were
      retrieved, 126 full-text articles were assessed after inclusion criteria and a
      final list of 30 articles was selected. No small-area deprivation measures that
      have been applied to the whole of Brazil were found. Existing measures were
      mainly used to study infectious and parasitic diseases. Few studies used the
      measures to assess inequalities in mortality and no studies used the deprivation
      measure to evaluate the impact of social programs. CONCLUSIONS: No up-to-date
      small area-based deprivation measure in Brazil covers the whole country. There is
      a need to develop such an index for Brazil to measure and monitor inequalities in
      health and mortality, particularly to assess progress in Brazil against the
      Sustainable Development Goal targets for different health outcomes, showing
      progress by socioeconomic groups.

PMID- 30183847
TI  - [Patient safety in the training practices of an undergraduate program in
      Occupational Therapy].
AB  - OBJECTIVE : To identify conditions and experiences about the patient safety in
      the academic practices of the Occupational therapy program of the Universidad
      Nacional de Colombia. METHODS: Descriptive cross-sectional study, with a sample
      composed of 29 students of academic practices of the program Occupational
      Therapy. A survey about safe customer assistance (electronic version) was
      designed and applied. The survey was rigorously validated and reviewed by
      experts. Each student gave consent to carry out the survey. RESULTS : The
      patients' falls are the ones that most frequently escape from the report or
      register on the practice area (47.1 % never report them). Despite that, falls are
      the most reported issue among other events (41.1 %). To a lesser extent, students
      always report incidents related to documentation and registration; equipment and
      health care devices (21.5 % and 28.6 %, respectively). In these two categories it
      is more prevalent to find several students who often report what actually happen
      (46.4 % in both cases). DISCUSSION : It is necessary to advance in the
      investigation of the causes and co sequences of events that affect the patient's
      safety in student practices, also in the provision of improvement measures that
      are efficient along with impact they have when implemented. Efforts are needed to
      transform the potential punitive perception that may be on the follow-up of
      measures track for patient safety. All the foregoing may be explaining part of
      the considerable under-reporting of incidents documented in the literature, in
      turn, going along with the findings of this study.

PMID- 30183848
TI  - [Safe water for rural communities from an alternative filtration system].
AB  - OBJECTIVE : Propose a prototype system for safe water treatment in Colombian
      rural areas. MATERIALS AND METHODS : The prototype consists of four chambers
      working on a water -clarification process using alum stone, also working on a
      filtration processes using granular materials such as different grain sizes of
      sand, pumice stone, activated carbon and gravel. The water problem was emulated
      based on the average water features found in the countryside and its monitoring
      mechanism tracked the current regulations in Colombia. RESULTS : There was a
      reduction of the fecal and total coliform of the 99.9 %, a reduction of the 98 %
      of turbidity, and of an 83 % of color. In all the cases, the records obtained
      enable to catalog the treated water as fit for human consumption. The pH,
      presented a slight increment due to the presence of pumice and other limestone in
      the filter material, but the measured value was included under the upper limit
      accepted for potable water. CONCLUSIONS : The treatment (purification) system
      evaluated in this study produced suitable water for human consumption obtained
      from countryside average water. The proposed technology is easy for adoption and
      diffusion and contributes to prevent water-borne diseases in areas without water
      systems.

PMID- 30183849
TI  - [Serum activity of CK and CK-MB in patients with dengue virus infection].
AB  - OBJECTIVE : To determine the serum activity of CK and CK-MB in patients with
      dengue infection. METHODS : A cross section study was conducted in the State of
      Antioquia, Colombia. The study population consisted in 54 patients with diagnosis
      of dengue infection and 10 healthy controls. A blood sample was taken from all
      participants to confirm dengue infection and to measure the activity of CK and CK
      MB. RESULTS : The median age of dengue cases was 18 years and the median age of
      healthy controls was 28.5 years. Half of dengue patients (50.9 %) had elevated
      levels of CK-MB, in contrast with the healthy controls in which none presented
      increase of this enzyme. No patient presented myocarditis; however, elevated CK
      MB was observed in 33.3 %, 44.4 % and 40 % of cases with bradycardia, tachycardia
      and hypotension respectively. In 29.6 % of the dengue patients, high level of CK
      was detected, in contrast to 10 % in the control group. Activity of CK elevated
      was observed in dengue patients with symptoms such as vomiting, hematemesis and
      abdominal pain, 87.5 %, 60 % and 50 %, respectively. CONCLUSIONS : In this study,
      no patient with dengue infection had heart disease or myositis; however, the
      finding of a higher frequency of elevated level CK and CK-MB in the dengue
      patients compared to the control group suggests the involvement of the striated
      muscle and of the cardiac muscle in this group. For this reason, the monitoring
      of these enzymes should be considered as part of the monitoring of patients with
      dengue.

PMID- 30183850
TI  - Assessment of hematological parameters in workers exposed to organophosphorus
      pesticides, carbamates and pyrethroids in Cundinamarca 2016-2017.
AB  - OBJECTIVE : To establish hematotoxic alterations through clinical and
      paraclinical exploration in workers who are exposed to organophosphorus
      pesticides, carbamates and pyrethroids (OPCP) due to their work in production,
      packaging, distribution and fumigation processes in Cundinamarca-Colombia between
      2016 and 2017. MATERIALS AND METHODS : A cross-sectional descriptive
      epidemiological study was carried out on a sample of 92 workers from six
      companies, mostly aged between 18 and 30 years, of which 61 % were males and 39 %
      females, and 71 % were workers in the operational area and 29 % in the
      administrative area. Univariate, bivariate and multivariate analyses were
      performed. RESULTS : Clinical exploration reported findings in 17 % of the sample
      group, of which only 2 % presented with erythrocyte cholinesterase outside the
      reference range. The values of hematological parameters such as peripheral blood
      smear (PBS) and complete blood count (CBC) were outside the range in 15 % and 47
      % of the sample, respectively. DISCUSSION : The results suggest that there are
      hematological alterations in this group that could possibly be associated with
      chronic exposure to OPCP.

PMID- 30183851
TI  - [Analysis of conglomerates for the study of social inequalities due to
      cardiovascular diseases].
AB  - OBJETIVE : To establish social inequalities in mortality from cardiovascular
      diseases in the municipalities located in the "triangulo del cafe". METHODS :
      Ecological design that measured social inequalities in mortality due to
      hypertension, ischemia and stroke according to economic indicators in the
      municipalities located in Caldas, Quindio, and Risaralda. Mortality for
      calculating rates and Unsatisfied Basic Needs (NBI) were obtained from the
      National Statistics Department; the Gross Domestic Product (GDP) was calculated
      for the study. A multivariate cluster analysis was used grouping the
      municipalities into classes according to the similarity in their characteristics.
      RESULTS : Three classes were identified: municipalities of the first class have
      the highest per capita GDP, the lowest BIN, the highest mortality rate for
      stroke, the lowest mortality rate for the lowest hypertension. Class two has the
      lowest per capita GDP and the highest mortality rate for ischemic. Class three
      has the highest NBI, the highest average in mortality due to hypertension and
      ischemic. The conglomerate conformation suggests a relationship between a high
      BIN and the mortality rates due to hypertensive and ischemic. A high per capita
      GDP and low NBI with the mortality rate for stroke. CONCLUSION : No significant
      differences in the mortality rates due to stroke, ischemic or hypertension, in
      the various states under study were observed.

PMID- 30183852
TI  - [Socio-cognitive development in early childhood: the challenges to reach in
      public health at the area of Sabana Centro and Boyaca].
AB  - OBJECTIVE : The need to build public health systems that ensure comprehensive
      child development enables a characterization of the factors that favor or
      restrict the integral development of children under the age of six. That is in
      order to identify them as necessary components to be taken into account in public
      policies. METHOD : A survey was carried out with 1 177 mothers or family
      caregivers of children under six years old in 16 municipalities of Cundinamarca
      and Boyaca, and the respective socio-cognitive development of their own sons and
      daughters was measured with the Haizea-Llevant table and also tasks related to
      the use of core knowledge systems. RESULTS : Through bivariate and multivariate
      statistical analyzes, it was found that the factors that are significant to
      address a public health proposal that seeks the integral development of children
      under six years of age are: socio-economic conditions of households,
      complications in childbirth, the starting age of solid foods, mothers' working
      shifts, rules on daily routines and play practices such as reading, painting and
      sport activities. CONCLUSIONS : A health system that acknowledges the results
      presented should offer specialized care that seeks welfare in childhood and early
      childhood, which can only be achieved if health policies begin to consider
      domestic and daily factors that cannot be excluded from public policies and it
      should guarantee different levels of intervention of social and particular
      impact.

PMID- 30183853
TI  - [Assessment of curricular contents and perception of competencies of health
      students related to the integrated health care model in Colombia].
AB  - OBJECTIVE : To identify the perception of the last level students of the
      professional and technical health training programs regarding their competences
      to perform in the MIAS, and to evaluate the presence of said competences within
      the curricular contents of the health programs in Santander. METHODS : A
      transversal descriptive study was carried out in 451 students and a documentary
      review of curricula was performed for 26 programs. The content of an online
      questionnaire on the perception of competences in the areas of knowledge,
      attitudes and abilities was constructed and validated. RESULTS : In the
      documentary review, deficiencies were found in the inclusion of competencies such
      as leadership (80 %) and differential approach in care (84 %). In the perception
      survey, 36 % of the students stated that they had regular or deficient knowledge
      about Integral Routes of Health Care, benefit plans and actors of the health
      system. Additionally, 7.5 % stated they were not competent to carry out
      intersectoral coordination activities, epidemiological surveillance or public
      health research. CONCLUSION: The results show the need to include in the
      curricula of health programs some fundamental aspects for the proper
      implementation of MIAS.

PMID- 30183854
TI  - [Metabolic syndrome in public service drivers in Armenia, Colombia].
AB  - OBJECTIVE : To characterize and compare the population of public service drivers
      of a transport company in Armenia, Colombia. MATERIALS AND METHODS : Taxi and bus
      drivers from a transport company of Armenia, Colombia participated in an
      Analytical cross-sectional study. The analysis of the variables was made through
      Statgraphics Centurion XVI. The comparison of variables as well as multiple and
      logistic regression were carried out. RESULTS : 125 individuals participated, 8
      were removed, and finally there were 117 male drivers as aim of research. The
      28.21 % of individuals have driven small buses and the 71.79 % have driven cars.
      The increase in alcohol consumption was remarkable compared to tobacco. The 60.69
      % of subjects did not get exercise. Besides, the BMI average and abdominal
      circumference was 28.03 kg/m2 and 100.09 cm respectively. The triglyceride
      average and serum HDL-C were 207.53 mg/dL to 33.12 mg/dL. 49.57 % of all drivers,
      fulfilled the Metabolic Syndrome diagnostic criteria. Statistically significant
      differences were found in the values of BMI, waist circumference, systolic blood
      pressure, diastolic blood pressure, weekly exercise, triglycerides and fasting
      glucose between individuals with and without Metabolic Syndrome. CONCLUSION :
      Public service drivers have a profile risk for developing Metabolic Syndrome.
      Obesity, hypertriglyceridemia and low HDL-C were the main alarm parameters of the
      presence of Metabolic Syndrome.

PMID- 30183855
TI  - [Reliability of neuroconduction studies in carpal tunnel syndrome].
AB  - OBJECTIVE : To determine the reliability of neuroconduction studies by comparing
      two observers and detecting minimum changes when diagnosing carpal tunnel
      syndrome. METHODS : Sixty-nine patients referred for electrophysiological study
      due to suspected carpal tunnel syndrome were studied. The patients underwent two
      examinations, performed by two evaluators, on two different days. Sensory and
      motor latencies of the median and ulnar nerves were evaluated; all were
      classified as negative, incipient, mild, moderate, severe or extreme. Relative
      interval variation, intraclass correlation coefficient, kappa index, limit of
      agreement and minimum detectable change were estimated. RESULTS : The relative
      variation of motor nerve latency of the median nerve was -6.8% to 15.9%, with
      intraclass correlation coefficient of 0.98 for the difference of median-ulnar
      nerve latency. The minimum detected change was 0.4ms, while the relative interval
      variation of sensory latency of the median nerve was -5.0% to 11%, with
      intraclass correlation coefficient of 0.95 for difference with the ulnar nerve.
      The minimum detectable change was 0.2ms. Electrophysiological classification
      agreed in 93% of the cases, with a kappa index of 0.89. CONCLUSIONS : Sensory and
      motor latencies of the median nerve, as well as the difference between them and
      the ulnar nerve, are reliable measures. The minimum detectable change obtained in
      our study helps clinicians to establish whether changes in latencies in
      consecutive or post-treatment studies are significant.

PMID- 30183856
TI  - [Quality of life and environment in communities close to industrial mining
      activity in Boyaca, Colombia].
AB  - OBJECTIVE : To compare the life quality perception and environmental situation,
      in nearby and distant towns from the mining industry of the Boyaca Department of
      Colombia. METHOD : Cross-sectional study. The towns near of influence area were
      grouped into zones 1 and 2, and distant towns as zone 0. Conglomerates carried
      out a simple, multistage, random sampling. A sample of 1,117 households was
      determined and the unit of analysis was the family. To measure the quality of
      life and health perception, the WHOQOL-BREF instrument was used. Frequency
      distributions and comparisons between qualitative and quantitative variables were
      calculated. Univariate and bivariate analyzes were performed. RESULTS : The life
      quality perception and satisfaction with health was greater in zone 0. The means
      calculated for the four domains of the questionnaire, by towns, shows that
      Ramiriqui has the highest interquartile ranges. The life quality perception
      decreases in women and with increasing age. In zones 1 & 2, the environment was
      described as "very bad" and without any improvement at the last five years.
      CONCLUSION : Communities close to mining-industrial activities report a worse
      perception of health, greater concern about the risk of exposure and do not
      consider that mining industry provides greater benefits for their quality of
      life.

PMID- 30183857
TI  - [Pain in dependent elderly people: home visit program culturally adapted to a
      rural population].
AB  - OBJECTIVE : To assess the effects of a culturally adapted home visit program on
      pain intensity in elderly people with disability and poverty conditions in the
      rural population of Caqueza-Cundinamarca, Colombia. METHOD : Quasi-experimental
      study with pre-test and post-test. The study included 34 people over 60 years of
      age with physical or visual impairment and total or partial dependence. The home
      visit program consisted of seven visits paid for an average of two hours and an
      interval of 13 to 15 days. A syncretism of drugs, medicinal plants and home
      remedies was proposed for pain management. Pain was assessed using the verbal
      pain scale and qualitative data were recorded in the field diary. Wilcoxon signed
      rank test was applied. RESULTS : During the pre-test, 100 % of the participants
      presented with a type of pain, while favorable and significant effects were
      observed in the post-test (p value <0.001) in relation to pain reduction. Changes
      are qualitatively attributed, partly, to the development of the program and other
      explanations include values and beliefs of the group. CONCLUSIONS : The
      culturally adapted home visits program shows that it is possible to act in
      contexts where dialogues occur between popular and professional knowledge,
      achieving a safe practice adapted to the cultural universe of people. Latin
      America requires professionals culturally sensitive to expressions and
      perceptions of pain, who are curious to explore, based on evidence, the
      therapeutic possibilities proposed by popular knowledge.

PMID- 30183858
TI  - [Comprehensive diagnosis in patients with morbid obesity; candidates for
      bariatric surgery and suggestions for preoperative treatment].
AB  - OBJECTIVE : The purpose of the study was to analyze and describe the
      psychological, metabolic, anthropometric and physical condition of obese
      candidates for bariatric surgery. This is in order to determine the preoperative
      intervention. MATERIAL AND METHODS : The population is made up of 24 obese
      candidates for bariatric surgery; five men and 19 women between 21 and 60 years
      old. The sample type is non-probabilistic, with non-randomised subjects chosen
      conveniently and volunteers. Psychological, anthropometric, metabolic and
      physical condition variables were evaluated. RESULTS : The average age of
      participants corresponds to 41.0 years old. Low levels of empathic joy were
      observed. Anxiety symptoms presented an intermediate level: 62,5 % presented
      minimal depression, 29,1 % presented slight depression, and 8,4 % presented
      considerable depression. Body weight averaged 99.1 kg, height 1.6 meters, Body
      Mass Index (BMI) 39.3, the percentage of fat mass and contour waist averaged 41.1
      118.0 centimeters in that order. With regards to plasma levels (mg / dl), the
      following were obtained: total cholesterol 192.9, 120.0 LDL cholesterol, HDL
      cholesterol, 43.3, 182.3 triglycerides, glycerin to 105.9; and distance covered
      in 6 minutes was 511.9 meters. CONCLUSIONS : The results provide information to
      determine best Preoperative intervention strategies; changing the lifestyles of
      patients, keeping the postoperative weight.

PMID- 30183859
TI  - A province-wide survey on self-reported language proficiency and its influence in
      global health education.
AB  - OBJECTIVE : Literature has reported that language is the most common barrier in a
      health care setting and a risk factor associated with negative outcomes. The
      present study reports the differences between nursing students who speak one
      language and nursing students who speak two or more languages (self-reported
      language proficiency) and their skills and learning needs in global health.
      METHOD : An observational cross-sectional study was performed among nursing
      students from five Ontario universities. A survey was designed to measure
      knowledge, skills and learning needs in global health. RESULTS : Students who
      speak more than two languages are more likely to have more interest in learning
      global health issues, such as health risks and their association with travel and
      migration (p=0.44), and social determinants of health (p=0.042). CONCLUSION :
      Language training is needed for nursing students to be able to face language
      barriers in health care settings and improve global health, locally and
      internationally.

PMID- 30183860
TI  - [Analysis of the main elements found in the missions of Brazilian hospitals
      accredited with excellence].
AB  - OBJECTIVE : To analyze the elements present in the missions of Brazilian
      hospitals accredited with an international standard of excellence. METHOD :
      Mission elements were obtained from the websites of the Brazilian hospitals
      accredited with an international standard of excellence. RESULTS : Of eight
      elements proposed by Pearce II (1982), the most relevant and frequent elements
      for the mission of hospitals were mentioning products and services and their
      competition. The studies also identified elements that are required but were not
      found in any of the missions analyzed, namely, geographical domain, survival,
      growth or profitability, and concern for public image. CONCLUSIONS : It is
      possible to observe that none of the missions analyzed presented the eight
      elements proposed by Pearce II (1982) to become efficient. This can affect the
      purpose of the organization, which is defined through its mission, thus
      compromising its role as an essential element of strategic planning.

PMID- 30183861
TI  - [Quality of life in the senior population of Cartagena, Colombia].
AB  - OBJECTIVE : To determine factors associated with the quality of life of the
      elderly in Cartagena in 2015. METHOD : Cross-sectional study on a population of
      107 604 senior adults, with a sample of 660 people. Two-stage sampling was
      carried out using the Pfeiffer test, socio-demographic survey, Yesavage
      depression scale, self-perceived health questionnaire, Barthel Lawton and Brody
      scale, Multicultural Quality of Life Index, and Duke Questionnaire. Descriptive
      statistics and a multivariate logistic regression model were used. The ethical
      aspects of human studies were considered. RESULTS : 657 people participated, with
      an average age of 71 years, predominantly female (55.7 %), with a stable partner
      (62.6 %), primary schooling (49.6 %), household occupation (52.8 %), residing in
      strata 2 and 3 (66.7 %), and living with an average of 4 people in the same
      household. Findings include high prevalence of adequate social support (89.5 %),
      no depressive symptoms of clinical significance (86.9 %), independence to perform
      basic activities (86.3 %) and instrumental activities of daily living (60.8%).
      Additionally, their health was perceived as good (51.4 %), and the quality of
      life related to health as excellent (87.4 %). The most frequent pathologies were
      cardiovascular (26.1 %). CONCLUSIONS : Quality of life was positively associated
      to the perception of adequate social support and independence to perform
      instrumental activities of daily living, and negatively to working or having a
      pension.

PMID- 30183862
TI  - [The role of rodents in the transmission of Leptospira spp. in swine farms].
AB  - Different species of rodents are potential transmitters of multiple zoonotic
      agents such as Leptospira spp., a spirochete that causes leptospirosis. This is
      an infectious disease that has a negative impact on pig production because it
      generates large productive, reproductive and economic losses. In swine farms, the
      most common rodent species are house mice (Mus musculus), brown rats (Rattus
      norvegicus) and black rats (Rattus rattus), which act as maintenance hosts for
      different serovars of Leptospira, contaminating the environment, food and water
      through urine, and putting human and animal health at risk. For this reason, the
      objective of this article is to describe the role of rodents in the transmission
      of Leptospira in swine farms. For this purpose, a bibliographic search was
      carried out in different databases such as Science Direct, Scopus, Redalyc,
      PubMed and SciELO. The results of the literature review show that there are few
      studies that report the importance of rodents in the transmission of Leptospira
      in swine farms. The onset of the disease depends to a large extent on the
      presence, contact and control of rodents in farms, although environmental
      factors, agent survival and hygiene, among others, must also be considered.

PMID- 30183863
TI  - [Arterial hypertension and determinants in Venezuela].
AB  - OBJECTIVE : To determine the prevalence and determinants of arterial hypertension
      in the Venezuelan population. METHODS : A systematic review of the literature was
      performed in the PubMed and LILACS databases. The inclusion criteria were
      hypertension, Venezuela and risks. Articles published in any language were
      chosen, with no time limit. RESULTS : Out of 90 articles found during the search,
      only 20 met the inclusion criteria. Most of the data come from studies conducted
      in the central region of the country. The prevalence of hypertension found in the
      rural area is 33 %, while it oscillates between 24 and 31 % in the urban area,
      and 2.5 % in children. The studies showed that modifiable determining factors
      include obesity and dyslipidemias. In turn, non-modifiable factors include family
      history, race and age. CONCLUSIONS : Data are insufficient to establish the
      prevalence of the disease in Venezuela and its determinants. It is recommended to
      encourage multicenter prevalence studies that cover the entire country. Studies
      should be regularly done over time (longitudinal studies) to describe the
      increase or not in prevalence.

PMID- 30183864
TI  - [Work Disability Prevention: an area of study needed to address the Colombian
      system challenges in occupational risks].
AB  - This paper aims to address the importance of study, introduce and implement the
      issue of prevention and management of work disability in Colombia. Text structure
      responses to questions ranging from the current situation of workers and their
      health in Colombia, from the importance of studying this subject; the approach of
      the determinants of work disability; its definition, to the challenges settled
      for different actors in the Sistema Nacional de Seguridad Social involved in the
      process of prevention, care, rehabilitation, compensation, and return home.

PMID- 30183865
TI  - [Contaminants in food and nutritional guidance: theoretical reflection].
AB  - Reflection study on the nutritional guidelines given to the population, which, in
      most parts of the world, emphasize on the consumption of fruits, vegetables and
      legumes over industrialized foods, which contain more sugar, sodium and calories,
      and increase body weight. However, when one reads about the ways of cultivating
      fresh food and about the quality of meat and fish products destined for
      consumption, the question arises as to whether there is coherence between said
      guidance and consumption, given that there are reports of contamination of these
      foods by pesticide residues, as well as soil and water contamination, a topic
      scarcely addressed by state entities. What should be done to face this reality? A
      viable perspective is to raise awareness in the population, which should demand
      better quality foods, in addition to returning to healthier practices such as the
      cultivation of home-grown organic gardens and acquiring as few industrialized
      foods as possible. Far from causing controversy, this reflection aims to
      encourage a critical view in health professionals on their role in disease
      prevention and the demand for healthier foods for human consumption.

PMID- 30183866
TI  - Service users' perception about healthcare provided by teams participating in the
      National Program for Primary Care Access and Quality Improvement in Brazil.
AB  - OBJECTIVE: to analyze service users' perception of health care provided by the
      teams participating in the National Program for Primary Care Access and Quality
      Improvement (PMAQ-AB) in Brazil. METHODS: this was a cross-sectional study using
      data from interviews with users of services provided by PMAQ-AB teams in 2012.
      Multinomial logistic regression was used to analyze the association between
      perception level (very good/good, regular, poor/very poor) and variables of four
      primary care attributes: accessibility, integrality, longitudinality and care
      coordination. RESULTS: out of 65,391 users, 78.9% evaluated care as very
      good/good, 19.0% as regular and 2.1% as poor/very poor. Associations with care by
      the same physician (OR 3.21; 95% CI 2.68, 3.83) and physical examination at
      consultation (OR 3.08; 95% CI 2.50, 3.79) were the most prominent. CONCLUSION:
      the majority of users evaluated care positively, however there is perception of
      care problems within the recommended attributes.

PMID- 30183868
TI  - Time trend of Family Health Strategy coverage in Brazil, its Regions and
      Federative Units, 2006-2016.
AB  - OBJECTIVE: to analyze the Family Health Strategy (FHS) coverage time trend in
      Brazil, its Regions and Federative Units (FUs) in 2006-2016. METHODS: this was an
      ecological study with time series analysis of Ministry of Health Primary Care
      Department data; Prais-Winsten regression was used. RESULTS: FHS coverage in
      Brazil in 2006 and 2016 was 45.3% and 64.0%, respectively, with an increasing
      trend of coverage (annual variation = 8.4%: 95%CI 7.4;9.3); all five regions
      showed an increasing trend in coverage, as did the majority of FUs, with the
      exception of Roraima, Amapa, Piaui, Rio Grande do Norte and Paraiba, which showed
      stability; in 2016, 14 FUs had coverage of between 75 and 100%, and 11 had
      coverage of between 50 and 74,9%; coverage in Sao Paulo and Federal District was
      below 50%. CONCLUSION: although, overall, FHS coverage increased, 13 FUs
      presented coverages below 75% in 2016; therefore, more efforts are needed to
      universalize coverage.

PMID- 30183867
TI  - Chikungunya surveillance in Brazil: challenges in the context of Public Health.
AB  - OBJECTIVE: to describe the challenges in implementing the chikungunya
      surveillance and prevention system in Brazil. METHODS: this was a descriptive
      study of suspected cases of the disease based on records held on the Notifiable
      Diseases Information System (Sinan) for the period 2014-2016. RESULTS: more than
      100,000 probable chikungunya cases were notified in Brazil in this period, with
      the largest concentration in the Northeast states (83.3% between 2014 and 2015;
      91.0% in 2016); Sinan provided an excellent opportunity for closing records of
      cases occurring between 2014 and 2015 (85%) and high completeness of obligatory
      variables. CONCLUSION: given the imminence of the introduction of chikungunya in
      Brazil in 2014, advance public health preparation took place in order to minimize
      its effects on society; implementation of the surveillance system improved
      collection of information regarding the disease, however many challenges can be
      seen in practice, in view of increasing case incidence. This requires greater
      handling capacity in this sector.

PMID- 30183869
TI  - Analysis of the process of malaria transmission elimination with a spatial
      approach to incidence variation in the Brazilian Amazon, 2016.
AB  - OBJECTIVE: to identify areas where malaria transmission has been eliminated and
      levels of malaria incidence variation in the Brazilian Amazon in 2016, and to
      present an indicator of priorities for control actions. METHODS: an ecological
      study was conducted with data from the Malaria Epidemiological Surveillance
      Information System (Sivep-Malaria); municipalities were classified into three
      groups - elimination achieved, in the process of elimination and in search of
      reduction -; a composite indicator was created to stratify municipalities
      prioritized for control actions. RESULTS: a total of 337 (41.7%) municipalities
      were found to have achieved elimination, 398 (49.3%) were in the process of
      elimination and 73 (9.0%) were in search of reduction; the priority indicator
      created identified 71 municipalities that accounted for 95% of cases. CONCLUSION:
      the vast majority of municipalities have already achieved elimination of malaria
      transmission or are in the process of eliminating transmission; the priority
      indicator may contribute to targeting malaria control actions.

PMID- 30183871
TI  - Sexual aspects of liver transplant candidates and recipients: evidence available
      in the literature1.
AB  - OBJECTIVE: to analyze the evidence available in the literature on the alterations
      in the sexuality of candidates and recipients of liver transplantation. METHOD:
      integrative review of the literature with search for primary studies in the
      databases MEDLINE (via PUBMED), CINAHL e LILACS, published in English, Portuguese
      and Spanish. RESULTS: the 16 primary studies included were grouped into three
      categories: 1) female sexuality (n=5), 2) male sexuality (n=5) and 3) male and
      female sexuality (n=6). In category 1, the subjects investigated were
      contraception, pregnancy, sexual dysfunction, presence of gynecological symptoms
      and sexually transmitted infections. In category 2, the main focus of the studies
      was erectile dysfunction, sexual desire and satisfaction, and consequences of the
      immunosuppressive regimen with mycophenolic acid in men. In category 3, the
      evaluation of sexual function was the main topic. CONCLUSION: the scientific
      evidence generated provides support to encourage health professionals to
      incorporate the topic of sexuality in the routine of care. Knowledge gaps were
      identified and new studies should be conducted in order to implement
      interventions to prevent, minimize and/or control changes related to the
      patient's sexuality.

PMID- 30183870
TI  - Predictors of well-being and quality of life in men who underwent radical
      prostatectomy: longitudinal study1.
AB  - OBJECTIVE: to identify socio-demographic, clinical and psychological predictors
      of well-being and quality of life in men who underwent radical prostatectomy, in
      a 360-day follow-up. METHOD: longitudinal study with 120 men who underwent
      radical prostatectomy. Questionnaires were used for characterization and clinical
      evaluation of the participant, as well as the instruments Visual Analog Scale for
      Pain, The Ways of Coping Questionnaire, Hospital Depression and Anxiety Scale,
      Satisfaction with Social Support Scale, Marital Satisfaction Scale, Subjective
      Well-Being Scale and Expanded Prostate Cancer Index. For data analysis, the
      linear mixed-effects model was used. RESULTS: the socio-demographic factors age
      and race were not predictors of the dependent variables; time of surgery, problem
      focused coping, and anxiety were predictors of subjective well-being; pain,
      anxiety and depression were negative predictors of quality of life; emotion
      focused coping was a positive predictor. Marital dissatisfaction was a predictor
      of both variables. CONCLUSION: predictor variables found were different from the
      literature: desire for changes in marital relationship presented a positive
      association with quality of life and well-being; emotion-focused coping was a
      predictor of quality of life; and anxiety was a predictor of subjective well
      being.

PMID- 30183872
TI  - Serious games as an educational strategy to control childhood obesity: a
      systematic literature review1.
AB  - OBJECTIVES: to identify in the literature the efficacy of serious games to
      improve knowledge for and/or behavioral changes among overweight or obese
      children. METHOD: Systematic Literature Review. The Cochrane Systematic Reviews
      Handbook was used. The studies were collected from the following databases:
      Public Medline; Web Of Science; Science Direct; Latin American and Caribbean
      Health Sciences Literature; and the Health Game Research and Cumulative Index to
      Nursing & Allied Health Literature. The descriptors were video games and obesity,
      while the key word was serious games. Inclusion criteria were: studies classified
      as Randomized Clinical Trials written in English, Spanish or Portuguese and in
      which children were the subjects of the study. RESULTS: 2,722 studies were
      identified in the initial search and six studies remained in the final sample.
      The papers focused on encouraging behavioral changes in players, including
      physical exercise and improved eating habits. The studies report that serious
      games are a potential strategy to encourage positive coping with childhood
      obesity. CONCLUSION: research in this field is an expanding and promising
      strategy and serious games represent an alternative means to provide health
      education to children.

PMID- 30183873
TI  - Relationship between anxiety, depressive symptoms and compulsive overeating
      disorder in patients with cardiovascular diseases.
AB  - OBJECTIVES: to identify the presence of compulsive overeating disorder in
      patients with cardiovascular diseases and to verify its relation with
      sociodemographic, clinical variables and the presence of anxiety and depressive
      symptoms. METHOD: cross-sectional, correlational study with a sample of 111
      patients with cardiovascular diseases. The presence of anxiety and depressive
      symptoms was assessed by the Hospital Anxiety and Depression Scale instrument and
      compulsive overeating disorder was assessed through a likert instrument called
      the Periodic Eating Disorder Scale (Binge Eating Scale). RESULTS: there was a
      predominance of patients without compulsive overeating disorder (n=91, 82%),
      followed by moderated compulsive overeating (n=15, 13.5%) and severe (n=5, 4.5%)
      associating to high levels of body mass index (p=0.010) and the presence of
      anxiety (p=0.017). CONCLUSION: Compulsive overeating disorder was present in 18%
      of the patients, being associated with body mass index and anxiety, suggesting
      that health professionals should pay attention to the comprehensive evaluation of
      patients with cardiovascular diseases. Important results emerged from this study,
      emphasizing the need to implement programs to improve the patients' mental and
      physical health in both primary and specialized care services.

PMID- 30183874
TI  - Effect of the board game as educational technology on schoolchildren's knowledge
      on breastfeeding1.
AB  - OBJECTIVE: to evaluate the effect of the board game as an educational technology
      on schoolchildren's knowledge on breastfeeding. METHOD: cluster-randomized
      clinical trial, held in nine schools, with 99 children in the third grade of
      elementary school (control group = 51 and intervention group = 48). The pretest
      was conducted in both groups; intervention consisted in the application of the
      educational technology immediately after pretest to the intervention group; and
      the post-test was applied on the 7th and 30th days to both groups. For the
      analysis of children's knowledge on breastfeeding, we considered the pre- and
      post-test score means, using the Mann-Whitney test - for comparing the means
      between groups - and the Wilcoxon test - within the same group. RESULTS: there
      was no statistically significant difference between the groups in the pretest. In
      the follow-up, when comparing the groups, there were higher means in the
      intervention group, on the 7th (19.68 +/-1.788) and on the 30th (20.16+/-1.260)
      days, with statistically significant difference. Within the intervention group,
      there was significant increase of the means in the pretest (15.89+/-3.082) for
      the 30th day (20.16+/-1.260). CONCLUSION: such educational intervention has
      significantly contributed to the increase in scores of children's knowledge on
      breastfeeding for the intervention group. UTN: U1111-1184-7386.

PMID- 30183875
TI  - Action of ear acupuncture in people with chronic pain in the spinal column: a
      randomized clinical trial1.
AB  - OBJECTIVES: to assess the action of ear acupuncture on disability and tissue
      temperature in people with chronic pain in the spinal column. METHOD: a clinical
      trial with a sample of 110 people, randomized into three groups: Treatment,
      Placebo and Control. The assessment instruments were the Rolland Morris
      Disability Questionnaire (RMDQ) and a thermographic camera, administered before
      the first treatment session, one week after and 15 days after (follow-up) the
      fifth session of ear acupuncture. In the analysis of the data, the Kruskal
      Wallis, Student-Newman Keuls and Wilcoxon tests were applied. RESULTS: there was
      a significant reduction in disability in the Treatment and Placebo groups between
      the initial and final assessments (p<0.05) and between the initial assessments
      and follow-up (p<0.05). In the final assessment, the Treatment group presented
      improvement of disability when compared with the Placebo and Control groups
      (p<0.05). There was an increase in mean tissue temperature of the dorsal region
      between the initial and follow-up assessments in Treatment and Control groups
      (p<0.05), and between the final assessments and follow-up in the Treatment and
      Placebo groups (p<0.05). CONCLUSION: ear acupuncture was efficacious in reducing
      disability and increasing tissue temperature in people with chronic pain in the
      spinal column. Brazilian Register of Clinical Trials (RBR-5X69X2).

PMID- 30183876
TI  - Scientometric overview of nursing research on pain management.
AB  - OBJECTIVE: to analyse research articles on pain and nursing issues using
      bibliometric and scientometric methodologies. METHOD: articles in the Web of
      Science database containing pain and nurse and pain and nursing were analyzed
      using scientometric methods through data visualization techniques and advanced
      text analytics. RESULT: among the 107,559 research articles found in the field of
      nursing, 3,976 of them were written based on the keywords pain and nursing, and
      were considered in conformity with the scope of this study. Preliminary analyses
      indicated that the publications have increased through the years with minor
      fluctuations. Titles, keywords, and abstracts were analyzed through text
      analytics to reveal keyword clusters and topic structures. Studies on oncology
      and pain in the field of nursing have a relatively higher frequency. CONCLUSION:
      the results of the analyses revealed the characteristics of the current
      literature in a broad range of areas by considering the particular dimensions.
      Therefore, the findings may support present and future research in this field by
      shedding light on the networks, trends, and contents in the related literature.

PMID- 30183878
TI  - [Determinants of infant mortality in Colombia. Path Analysis].
AB  - OBJECTIVE : To disentangle the singular effects of biological, environmental,
      socioeconomic, and medical factors on the probability for infants to die.
      MATERIALS AND METHODS : Apply a Path Analysis to Colombia's complete records of
      infant births and deaths, and the availability of maternal and child health
      services, during 2003-2009. RESULTS : From a biological perspective, a high birth
      weight resulting from a normal gestational age is the most important variable to
      ensure the infant's survival. Prenatal care is key to reduce infant mortality.
      From a socioeconomic perspective, high levels of education and relative access to
      high quality care in the contributory social health insurance regime for maternal
      residence, contribute to higher chances of infant survival. CONCLUSIONS : Related
      findings suggest that augmenting access to maternal, child and intensive care
      beds supported by the subsidized regime can reduce infant mortality.

PMID- 30183879
TI  - [The Kangaroo Mother Care Program of Yopal, Colombia: an opportunity to keep
      track of preterm infants].
AB  - OBJECTIVE : In Colombia, the incidence of prematurity and low birth weight (LBW)
      is 12.8%. To describe a standardized follow-up until 12 months of 1138 premature
      and/or LBW included in the Yopal KMCP (2014 -2015). MATERIALS AND METHODS :
      Prospective cohort. RESULTS: the patients are from the subsidized health care
      system (Colombia government), 58.2% live in the city and 24.6% at more than two
      hours from the city; 80.6% of parents are stable couples and 78.9% are employed;
      69% of mothers started prenatal control from the first trimester. The most
      frequent obstetric pathologies were urinary tract infection and pre-eclampsia;
      97% of deliveries were in the hospital; 55% by caesarean section. Majority of
      infants were late preterm; 13.3% passed through the Neonatal Intensive Care Unit
      (NICU) with 27% ventilated and 5.9% oxygen-dependent at discharge. At 6 months
      more than 50% had exclusive breastfeeding. Ophthalmology screening was performed
      in 54% (4.6% retinopathy), optometry in 72% and audiology in 70% (4.7% with
      hearing deficit). At 12 months 4.4% had abnormal neurological exam and 95%
      complete vaccines schedule. Lost to follow up was 35% and mortality 0.4%.
      CONCLUSION : It is important to implement KMCP in intermediate and isolated
      cities to ensure a high-risk follow-up for all LBW and / or premature babies, to
      detect somatic, sensory or neuro-psychomotor development anomalies and to perform
      timely interventions.

PMID- 30183880
TI  - [Factors associated with susceptibility to cigarette consumption in 10 and 11
      year old school students from Cartagena, Colombia].
AB  - OBJECTIVE : To determine associated factors to susceptibility to smoking in
      school students between 10 and 11 years old from Cartagena, Colombia. METHOD : A
      cross-sectional analytical study was conducted with a nonrandom convenience
      sample of 289 students between 10 and 11 years old of sixth-grade from public
      schools in Cartagena, Colombia. The information was collected through the
      demographic profile, the scale of susceptibility to persuasion towards
      consumption, the family Apgar scale, Rosenberg for self-esteem and Zung anxiety
      scale, and the smoking use inventory together with the attitudes on it, according
      to the Encuesta Mundial Sobre Tabaquismo en jovenes (Emtajoven). RESULTS : 289
      students, mean age 10,9 (SD = 0,25) participated, 157 (54,3%) were women and 132
      (45,7%) were men. The frequency of cigarette consumption for at least once in
      their lives was 20 (6,9%), and the high persuasion susceptibility was 61 (21,1%).
      Factors associated with high persuasion susceptibility to smoking cigarette were:
      being male (OR: 2,8 and CI 95% 1,6 to 5,1), family dysfunction (OR: 2,3 CI 95%
      1,2 to 4.2) and having ever smoked once in life (OR 3,4 CI 95% 1,3 to 8,7).
      CONCLUSIONS : Susceptibility to smoking among students of 6th grade is associated
      with being male, family dysfunction and having ever smoked in life.

PMID- 30183881
TI  - [Monitoring and impact of the disclosure of five health alerts for drugs in
      Colombia].
AB  - OBJECTIVE : Make the notification and monitoring compliance with five health drug
      alerts to a group of health care providers in Colombia. METHODS : Quasi
      experimental, prospective, before-after study, without control group, by
      intervening in physician prescribers of ketoconazole, metoclopramide, nimesulide,
      diacerein, strontium ranelate. The affiliated population of the contributory
      system of the Colombian Health System was taken as the universe population sample
      from 13 health promoting entities (EPS) of Colombia. Patients receiving monthly
      these drugs prior to the alert were identified. An educational intervention was
      performed and then the rate of change in the dispensation was measured. RESULTS :
      About 26 different activities were conducted on 500 prescribers. Out of a total
      of 4 121 954 people, 13 979 patients were identified monthly in 2013, who
      received some of the five medications. Likewise, a reduction in 1,470 subjects
      per month (-10.5%) for 2014 was observed. The drug which achieved the greatest
      reduction was ketoconazole (-31.1% of cases), followed by strontium ranelate (
      30.3%) and metoclopramide (-8.6%). For nimesulide (+ 0.7%) and diacerein (+
      16.4%) no favorable results were obtained. CONCLUSIONS : Patients with
      potentially risky prescriptions remain in Colombia; educational pharmacovigilance
      interventions made after the report alerts given by drug regulatory agencies may
      decrease the proportion of patients using these drugs.

PMID- 30183882
TI  - [Evaluation of the need for specialists in oncology, Bogota, Colombia, 2015].
AB  - OBJECTIVE : To evaluate the need of oncologists for cancer care in Bogota.
      MATERIAL AND METHODS : The Ministerio de Salud y Proteccion Social de Colombia
      (SISPRO) consultation report of malignant neoplasms is compared to a model of
      four treatment consultations and two of controls per year, according to the
      estimation of incidence and prevalence. Based on these data, the need for
      oncologists is calculated and compared with the registry that this ministry has
      of independent professionals (private practice in the office) and public and
      private health care institutions. RESULTS : When comparing the consultations made
      with those estimated for the care, it Is found that the indispensable
      consultations are not met with notable exception in lymphomas and leukemias, with
      more consultations than expected, and in ovary cancers, thyroid, cancers in other
      body parts and unspecified. The productivity of professionals in relation to the
      number of independent professionals is low, with excess supply in surgical
      oncology specialties except for urology; and there is a deficit in hematology
      oncology, clinical oncology and radiotherapy. But in this last situation, when
      including other sources, it is not found that the number of these specialists is
      lower than required. CONCLUSIONS : The oncological surgical specialties have an
      oversupply in Bogota except for urology, while clinical oncology and
      radiotherapy, that have a number under the register of independent professionals,
      are supplemented by physicians from public and / or private health care
      institutions.

PMID- 30183883
TI  - [Policies of zoonosis in Colombia: from health Code to environmental health].
AB  - OBJECTIVE : To analyze public policies of zoonosis in Colombia, in the period of
      1975 to 2014, as State responses. METHODOLOGY : Used the policy cycle analysis
      approach or sequential approach. This analysis was carried out by means of the
      following aspects: content, processes, actors, and vertical and horizontal
      relationships between policies. RESULTS : Zoonosis policies were very different
      in scope, contents and forms, and results are part of a history of successes and
      failures, who have only managed to partially transform the general and regional
      overview of the zoonosis. CONCLUSIONS : The implementation of decisions that have
      operational scope is relatively slow and scattered in areas of zoonosis in the
      country. A major achievement has been the shift from policies that are
      individualized to the great policy of health environmental-PISA.

PMID- 30183884
TI  - [Occupational therapy in oncology: experiences in academic practices and
      literature review].
AB  - OBJECTIVE : To inquire about the training of occupational therapists in oncology
      in a university program, and to identify updated literature as evidence for
      training and professional practice. MATERIALS AND METHODS : Cross-sectional
      exploratory study, with a sample of 29 students of occupational therapy from the
      National University of Colombia. Systematic review of literature 2010-2015 on
      occupational therapy interventions in oncology. Results In the survey, less than
      a quarter of the students reported having received training on clinical
      management of this diagnosis, and on the intervention of the occupational
      therapist with such cases (24.1%). Little more than this percentage (27.6%), has
      had users with cancer in their academic practices. In the literature review no
      national publications were found, although there were unpublished products from
      Colombian universities. Fifty-four international publications were recovered,
      especially in rehabilitation, it followed by psychosocial and socio-occupational
      areas. The palliative care, the multidisciplinarity, the subjective experience of
      the patient in relation to the diagnosis and treatment, the humanized and
      integral care from the different areas of the therapeutic task and work with
      caregivers are considered as relevant issues in the oncological patient's
      approach. CONCLUSIONS : Reference points are made for the occupational therapy
      curriculum development and for professional updating processes, which are both
      competence of the academy and of the guild. It is important to intervene in
      cancer not only during, but in the preparation to treatment and subsequently with
      survivors. Professional publications should be encouraged, making sure they
      provide powerful evidence of the impact of occupational therapy and oncological
      rehabilitation.

PMID- 30183885
TI  - [Satisfaction, health and work-related stress of the university professorship
      according to their contractual status].
AB  - OBJECTIVE : There's a lot of literature about teachers' work conditions and the
      effects of such conditions on them. The goal of this research focuses on the
      analysis of the effects derived from the type of labour relationship with the
      University on the psycho-social dimensions of satisfaction, stress and perceived
      health. METHODS : Quasi-experimental study on a sample of 145 university
      professors from the seven public universities from Catalonia (Spain). The data
      was obtained in April 2014, by means of ISTAS21 questionnaire, intermediate
      version, in Spanish. From the 21 subscales in the instrument, only seven were
      used for data-gathering since they encompassed the dimensions of interest. A
      series of ANOVA analyses were performed, taking the three psycho-social
      dimensions as dependent variables and work stability and dedication (e.g. full-
      vs. partial-time) as independent variables. RESULTS : Professors with full-time
      work and unstable contracts showed worse health (both physical and mental)
      despite being the youngest, as well as larger symptoms of stress and lower job
      satisfaction, compared with full-time professors with stable contracts and even
      compared part-time-jobs professors. CONCLUSION : Job-stability seems to be a
      central variable in work-quality and health for the professors whose labour
      situation is unstable, something that influences both their teaching and research
      quality.

PMID- 30183886
TI  - [Malnutrition and structural poverty. Comparison of two schoolchildren cohorts
      from Puerto Madryn, Argentina].
AB  - OBJECTIVE : To assess nutritional condition in two cohorts (C) of children from
      households with different Unsatisfied Basic Needs (UBN) attending neighborhood
      schools in Puerto Madryn, Argentina. METHODS : A cross-sectional study on six to
      11 year-old children attending seven neighborhood schools surveyed in the periods
      2001-2006 (C1, n=2 040) and 2014-2016 (C2, n=1 696) was performed. Weight, height
      and body mass index were measured using the World Health Organization cut-off
      values for nutritional condition. Neighborhood structural poverty was determined
      with percent UBN from the 2001 and 2010 census. Chi2 was used to compare the
      prevalence of nutritional condition between C and UBN categories. RESULTS : In
      the seven neighborhoods analyzed, percent UBN was 0%-10% (n=3), 10%-25% (n=2) and
      25%-50% (n=1), without changes in the period 2001-2010. In the remaining
      neighborhood, UBN increased from 25%-50% to >50%. The nutritional evaluation of
      children showed significant differences in the prevalence of obesity in most
      schools, while low height-for-age and overweight prevalence was significant only
      in one school. Comparison of C1 and C2 only showed significant differences in the
      prevalence of obesity. CONCLUSIONS : Structural poverty rates in Puerto Madryn
      neighborhoods were mostly unchanged; however, the nutritional condition of
      children was different: while the prevalence of chronic malnutrition did not
      change or decreased, the prevalence of obesity increased in all neighborhoods.
      Our findings could help to determine changes in the context of resident
      population and identify vulnerable groups.

PMID- 30183887
TI  - [Effectiveness of mobile technology and weight gain in pregnant women in Callao,
      Peru].
AB  - OBJECTIVE : To evaluate the effectiveness of mobile technology in the appropriate
      weight gain of pregnant women. MATERIALS AND METHODS : A quasi-experimental
      study. The sample included 117 pregnant women attending health facilities at la
      Direccion Regional de Salud (Diresa), Callao. Messages were sent to 58 pregnant
      women who formed the experimental group to improve their lifestyles and
      assistance to prenatal care (APC), while 59 pregnant women received routine
      education provided for pregnants. Messages were sent every three days. The
      nutritional status of the pregnant women was evaluated using the pre gestational
      BMI at the first visit of the APC. The weight gain was obtained from the
      difference between pre-gestational weight and weight recorded during the last
      controls. RESULTS : The adequate weight gain was 27.6% of intervened pregnancies
      and 25.4% in the non-intervened. The 79.3% pregnant had six or more NPC in the
      group intervened and 54.2% in the non-intervened. The weight gain was excessive
      in 5.1% in the non-intervened pregnant and 1.7% in the intervened. The highest
      percentage of pregnant women with adequate weight gain (32.0%) was observed in
      the intervened pregnancies with pre-gestacional overwhegith. CONCLUSIONS : There
      was no statistic difference in the use of mobile technology for a proper weight
      gain between both study groups. There were greater fulfillment of APC in
      intervened pregnancies compared to the non-intervened (p<0.05).

PMID- 30183888
TI  - [Complicated Malaria in Choco: clinical findings and data comparison with the
      monitoring system].
AB  - OBJECTIVES : To describe the epidemiological and clinical cases of complicated
      malaria and to establish the concordance of this information in the surveillance
      system. METHODOLOGY : Information was obtained from medical records of cases
      reported in 2011 in the surveillance system and the Hospital San Francisco. We
      selected a clinical sample of 62 stories of 113 cases and health professionals
      reviewed the information. The presence of positive thick drop with one or more
      criteria of complication was taken into account to define if the clinical history
      corresponded to complicated malaria, according to guide national clinic and tab
      of the surveillance system. Statistical significance was determined with Chi
      square and the Kappa statistic. RESULTS : The 37.0% of cases presented a
      complication, 63.0% had two or more complications. Major complications were
      thrombocytopenia and severe anemia, followed by hepatic complication,
      hiperparasitemia, renal insufficiency and cerebral malaria. In 3 of the 54 cases
      intravenous artesunate was used, quinine was used in 59.2%. Comparison of
      demographic variables and parasitic species between history and the surveillance
      system show no significant difference but type of complication was almost nil.
      The major reported complications do not appear on the notification tab.
      DISCUSSION : Further studies need to be continued in order to contribute to the
      clinical characterization of malaria in the Department and Management
      interventions. Adjustments to format are recommended to strengthen analysis and
      decision-making.

PMID- 30183889
TI  - [Knowledge, attitudes, perceptions and community practices for urban malaria.
      Tumaco, Colombia].
AB  - OBJECTIVE : To describe the condition of malaria in the District 5 of San Andres
      de Tumaco-Narino-Colombia, with regards to knowledge, attitudes, perceptions, and
      community practices. METHODS : A cross-sectional study was conducted between
      January and May 2014. Logistic analysis of the CAP-PP survey of the Pan American
      Health Organization (PAHO) was carried out. Statistical modeling was adjusted
      through the logarithm of likelihood test, the Pseudo R2, the Akaike's Information
      Criterion (AIC) and the Bayesian Information Criterion (BIC). Results. The
      variables that influence the disease of malaria are: taking medicines, malaria
      tests and vector control by spraying at home. It is important to keep clean
      ditches around the house in order for people to be protected against the disease.
      CONCLUSION : Although the population reported having knowledge, attitudes,
      community practices, and perceptions about the issue, these do not generate
      protection against the disease. Variables such as carrying out activities in the
      family and ignorance about the name of the mosquito that transmits malaria must
      be taken into account for the formulation of community intervention plans.

PMID- 30183890
TI  - [Urban outbreak of leishmaniasis in Colombia].
AB  - OBJECTIVES : To describe the epidemiology, clinical characteristics and treatment
      of children with visceral Leishmaniasis in Neiva- Huila, from April to June 2012.
      METHODOLOGY : We performed a descriptive study of an outbreak of visceral
      leshmaniasis in children from the urban area of Neiva. RESULTS : There were seven
      cases in children younger than five years. All of them had prolonged fever,
      hepato-splenomegaly, severe anemia and leukopenia. Five were admitted with severe
      thrombocytopenia, without hemorrhagic manifestations. Six patients received first
      line treatment with miltefosine, five of them had treatment failure requirirng
      therapy escalation to amphotericin B, two received liposomal amphotericin B and
      three deoxycholate amphotericin B. The main vector identified was the Lutzomyia
      gomezi and its main reservoir were canines. CONCLUSION : We describe the first
      visceral leishmaniasis outbreak in children living in an urban area, with no
      mortality. Most of the cases had a good response to amphotericin B.

PMID- 30183891
TI  - Molecular identification of clinical isolates of Fusarium in Colombia.
AB  - OBJECTIVE : Identifying Fusarium isolates from mycosis symptomatic patients
      through molecular techniques as PCR and sequencing. METHODS : In this study,
      samples were taken from 101 mycosis symptomatic patients in-between 2004-2006. To
      determine isolates belonging to the Fusarium genus, the DNAr 28S region was
      amplified through PCR and specific PCR primers further confirmed their identity
      to the species level. Additionally, in order to confirm the identity of the
      species of the isolates, 75 isolates of these were analyzed by partial sequencing
      of the 28S rDNA and the TEF1-alpha gene. RESULTS : The 28S rDNA portion detected
      all 101 isolates as belonging to Fusarium and the PCR specific primers detected
      52 and 29 isolates as F. oxysporum and F. solani, respectively; 34 and 41 of
      these, afterwards studied by partial sequencing of the 28S rDNA and TEF1- alpha
      genes respectively, were effectively identified by the technique. CONCLUSION :
      From all the molecular markers used to identify Fusarium isolates, the sequence
      of the TEF1-alpha gene provided the best resolution in the identification of
      species level; however it is possible to discriminate between F. oxysporum and F.
      solani isolates by PCR, in most of the cases, what is important considering the
      simplicity of the technique and a faster diagnosis.

PMID- 30183892
TI  - [Access to diagnosis of tuberculosis in Brazilian medium-sized municipality].
AB  - OBJETIVO : Evaluating access to tuberculosis diagnosis, from the perspective of
      patients. METHODS : Cross-sectional study with 108 tuberculosis patients. Data
      were collected using the brazilian instrument Primary Care Assessment Tool - PCAT
      Brazil, adapted for attention to tuberculosis, including socio-economic and
      demographic indicators, location of diagnosis and diagnostic access tuberculosis.
      The analysis of the data was of frequency, average, standard deviation,
      confidence interval and Chi-square test. RESULTS : Most cases were diagnosed in
      hospitals (52.8%). The patient sought the Health Unit on average three times
      until receiving medical care. The indicators of difficulty of displacement,
      expenditure on motorized transport and consultation within 24 hours to discover
      the disease were not satisfactory and regular. The chi-square test showed a
      statistical association between diagnosis location and seeking the nearest health
      unit from home. CONCLUSIONS : There are weaknesses in the early diagnosis of
      tuberculosis in primary care. There are many challenges to be faced to strengthen
      this level of health care, with organizational capacity to overcome the
      shortcomings related to the patient and the service that make it difficult to
      access the diagnosis of the disease.

PMID- 30183893
TI  - Training tuberculosis laboratory workers in LED-fluorescence microscopy:
      experience learned in Argentina.
AB  - OBJECTIVE : To assess a LED-fluorescence microscopy (LED-FM) capacitation program
      for the training of laboratory technicians without previous experience in FM.
      METHODS : We evaluated a teaching program that consists of a three-day course
      followed by an "in situ" two-month phase in which technicians acquired skills
      without the help of a FM expert; in order to gain confidence to recognize
      auramine-stained bacillus, during this phase, technicians examined duplicate
      slides stained by Ziehl Neelsen (ZN) and FM in a unblinded way. Technicians with
      acceptable performance, continued with a blinded-training period. Testing panels
      and rechecking process were used to evaluate proficiency after different length
      of experience. RESULTS : Post-course panel results showed that 70% of trainees
      made Low False Positive errors (LFPs). Analysis of two other panels showed that
      LFPs significantly decreased (Chi-squared test, p<0.05) as the "in situ" training
      phase progressed. Processing at least three slides/day was associated with
      acceptable performance. During the blinded-training period, results of the
      rechecking process showed that sensitivity (96.8%) and specificity (99.8%) levels
      were satisfactory. CONCLUSION : Moderate training (a three-day course) is not
      enough to make technicians proficient in LED-FM; however, great ability can be
      reached after a short "in situ" training phase even without the presence of
      experienced staff available in field to review doubtful results. Training was
      more effective in services with a minimum workload of 750 slides/year.

PMID- 30183894
TI  - [Theoretical evaluation of optimal and suboptimal antiretroviral therapy
      strategies for HIV infection].
AB  - HIV interaction with the immune response is modeled mathematically. Initially, a
      detailed model is proposed that consists of a system of differential equations
      including immune cells (antigen presenting cells, T latent infected cells, T
      actively infected cells, resting T cells, helper T cells, inactive cytotoxic
      cells and active cytotoxic cells) and viral particles. Then, stability conditions
      are given from the basic reproduction number and numerical simulations are
      performed. From this it is possible to conclude what are the most influential
      parameters to reduce infection. From the initial model, a control problem is
      formulated in order to determine the most appropriate type of intervention to
      ensure high levels of activated T cells and immune response. Five different
      control strategies based on antiretroviral are evaluated to conclude that a
      strategy of constant control, obtained as the average value of optimal control,
      provides satisfactory results.

PMID- 30183895
TI  - [Motorized mobility, environmental impact, alternatives and future prospects:
      considerations for the Area Metropolitana del Valle de Aburra].
AB  - Motorized mobility is closely linked to liquid fuels such as gasoline and diesel
      and therefore, to the environment. Besides the problems associated with global
      warming, the use of these fuels also generates polluting compounds affecting the
      population health. Among all primary pollutants, particulate matter (PM) less
      than or equal to 2.5 microns (PM25) in size, is regarded as one of the most
      dangerous compounds because it can penetrate the region lung gas exchange. The
      records for the Area Metropolitana del Valle de Aburra (AMVA) often show that the
      average levels of air quality were found to be harmful to the health of
      metropolitan habitants. This is mainly attributed to the high concentrations of
      PM25 generated by heavy-duty vehicles that use diesel fuel. Although the
      properties of diesel fuel have a direct effect on breathable PM, there are other
      strategies influencing both nature and amount of emissions. For example, the
      improvement of the technological level of the engines and the driving pattern, as
      well as the incorporation of electric vehicles. This paper shows some
      considerations in order to propose possible strategies to solve the environmental
      problem of the city and the country.

PMID- 30183896
TI  - [Approaching knowledge and experiences at a distance: report of the tutoring of a
      specialization course].
AB  - This report aims to describe the experience of tutoring process in distance
      learning of the Multidisciplinary Specialization Course in Primary Care in
      Brazil, in the states of Santa Catarina and Parana. Course participants were
      physicians, dentists and nurses included in the "Program for the Valorization of
      Primary Health Care" and the "More Doctors Program in Brazil", a total of 1 600
      professionals. The course was structured from three theoretical axes and
      pedagogical mediation conducted by a team of tutoring. . It was adopted
      problematization methodology, developed from a critical view of reality in the
      teaching and learning process. The tutors worked in pedagogical orientation,
      supporting use of media and technology and evaluation of educational activities
      in the course. The students evaluated positively the didactic and the course
      design and performance of the tutors. One hopes that this experience can be seen
      as a possibility to boost other experiences in health education.

PMID- 30183897
TI  - [Cryptosporidiosis and "One Health"].
AB  - Cryptosporidiosis is a diarrheal disease (zoonotic) caused by the parasite
      Cryptosporidium, which infects the intestine. It occurs in humans and in
      different pets, farm and wild animals. Its role is underestimated and little is
      known about its epidemiology, due to the low interest it draws and the limited
      availability of diagnostic methods. The population health, both human and animal,
      is related to a close interaction of three factors: the environment, pathogens,
      and population, which determines the state of health and disease; some of the
      diseases considered as emerging, that appeared in the last years. The approach,
      known as "One Health", is a growing global strategy being adopted by a diversity
      of organizations and policy makers in response to the need for integrated
      approaches. This approach may be relevant to a wide range of global development
      goals. There is more and more talk about holistic health. It seems that we are
      more aware that health is not reduced to something purely biological, but affects
      the whole person. It is not only seeing the patient globally, it is starting from
      the complexity of the human being and the whole world crossed by vulnerability
      and interacting with the totality of the subjects.

PMID- 30183898
TI  - [Water, Sanitation And Health].

PMID- 30183899
TI  - [Urinary Arsenic Concentrations In Adult Population Of Two Districts From The
      Tacna Region, Peru, 2017].
AB  - OBJECTIVES: . To determine the concentration of total urinary arsenic (As) in the
      adult population of two districts in the Tacna region. MATERIALS AND METHODS: . A
      cross-sectional observational study conducted in the districts of Cairani and
      Camilaca, in the province of Candarave in the Tacna region, Peru. For the study
      103 and 71 urine samples were collected. The concentration of urinary As was
      determined by the method of microwave digestion and flow injection in atomic
      absorption spectrophotometry (FIAS-AAS). RESULTS: . In the Cairani district, a
      median urinary arsenic concentration of 601.61 MUg/g creatinine (IQR: 407,3 -
      847,1) was obtained; and for Camilaca, a median of 30.24 MUg/g creatinine was
      obtained (IQR: 21,4 - 39,7). The residents of Cairani and Camilaca exceed 30 and
      1.5 times, respectively, the toxicity reference values (TRV) for arsenic.
      CONCLUSIONS
 .
 : The adult population of the districts of Cairani and Camilaca
      in the province of Candarave of the Tacna region has urinary As concentrations
      exceeding the toxicity reference values (TRV) established by the World Health
      Organization (WHO).

PMID- 30183900
TI  - [Comparison Of Anthropometric Measures For Aggregation Of Multiple Risk Factors
      In Adults Of Cuenca, Ecuador].
AB  - OBJECTIVE: . The aim of this study is to compare the predictive capacity of
      different anthropometric indices in multiple risk factors aggregation (MRFA)
      determination in the adult population from Cuenca city, Ecuador. MATERIALS AND
      METHODS: . A cross- sectional descriptive study was performed with a random multi
      stage sampling in 318 adult subjects who underwent a clinical, anthropometric and
      laboratory evaluation; being the abdominal circumference, body mass index (BMI)
      and waist height index (WHtR) evaluated. MRFA was defined as the presence of >=2
      components of the metabolic syndrome (excluding abdominal circumference). ROC
      curves were plotted to determine the area under the curve (AUC) for each index.
      RESULTS: . Of the 318 individuals, 54.1% (n=172) presented MRFA. According to ROC
      curves, the highest predictive capacity in women was observed with BMI and WHtR
      (AUC: 0.751 and 0.750, respectively), while in men abdominal circumference and
      WHtR showed a similar predictive power (AUC: 0.762). The multivariate analysis
      adjusted for sex and age showed that high WHtR (OR: 2.53, 95% CI: 1.12-5.71,
      p=0.026) was the best predictor of MRFA, followed by BMI (OR: 2.15, 95% CI: 1.19
      3.88, p=0.010). CONCLUSIONS: . The predictive capacity of the anthropometric
      indexes is influenced by gender; nevertheless the WHtR is the best predictor of
      MRFA in our population.

PMID- 30183901
TI  - [Effects of the endosperm of tara seeds and powder of Agave Americana leaves on
      body weight and intestinal transit time in holtzman rats].
AB  - OBJECTIVE: To evaluate the effects of endosperm of tara seeds (ETS) and powder of
      Agave americana leaves (AAL) on body weight and intestinal transit time in
      Holtzman rats. MATERIALS AND METHODS: Twenty-five male Holtzman rats,
      individually caged, and distributed into five groups were fed for 21 days with
      one of the following treatments: T1, diet with 6% alpha cellulose (Control); T2,
      diet with 6% ETS; T3, diet with 6% AAL; T4, diet with 10% ETS; and T5, Diet with
      10% AAL. Feed intake, body weight gain, apparent digestibility of fat,
      characteristics of feces (fat content, weight, moisture, volume, and pH) and
      intestinal transit time were recorded. One-way analyses of variance (ANOVA) were
      performed, as well as Tukey's multiple means comparison. RESULTS: Diets with 6%
      and 10% of ETS resulted in a reduction of feed intake, apparent digestibility of
      fat, and fecal pH, and said results had an effect in the reduction of body weight
      gain of 37.0% (p=0.008) and 50.9% (0.001), compared with the control diet. The
      diet with 10% of AAL powder reduced the intestinal transit time from 642 min
      (control) to 532 min (p=0.242). CONCLUSIONS: Diets containing EST regulated body
      weight gain, while the diet with AAL powder had no effects on the intestinal
      transit time in rats.

PMID- 30183902
TI  - [Influence of the consumption of quinoa on the biochemical parameters and
      intestinal histomorphometry in obese rats].
AB  - OBJECTIVE: . To determine the influence of the consumption of three varieties of
      quinoa on the biochemical parameters and intestinal histomorphometry in obese
      rats. MATERIALS AND METHODS: . A total of 42 obese Holtzman rats arranged in
      seven treatments of six animals each were used and fed during 23 days with one of
      the seven diets: an obesogenic control and the others six containing 20% of
      Altiplano, Pasankalla, or Negra Collana quinoas processed by cooking or roasting.
      At the end of the feeding period, blood samples were taken for the determination
      of glucose, triglycerides, and C-HDL levels; later, the animals were sacrificed,
      and the liver, small intestine, and kidneys were weighed. Small intestine samples
      were extracted for intestinal histomorphometry. Data were analyzed through ANOVA
      using GLM under a completely randomized design with 3x2 plus control factorial
      arrangement and comparison of means by Fisher test. RESULTS: . Glucose,
      triglyceride, and C-HDL levels did not differ compared to the control group; in
      addition, the weight of the kidneys was not affected by the experimental diets.
      However, the small intestine presented greater weight in the control group
      compared to those containing processed quinoa. Histomorphometry of the small
      intestine was not significantly affected by experimental diets. CONCLUSIONS.:
      Feeding obese rats with diets containing processed quinoa varieties does not
      modify the biochemical parameters and does not affect intestinal
      histomorphometry; however, it decreases the weight of the small intestine in
      obese rats.

PMID- 30183903
TI  - [Pathology of heart transplantation in peru: experience with 61 cases in a
      national reference center].
AB  - OBJETIVE.: To describe the histopathological characteristics of explanted hearts
      and post-transplant biopsy specimens at a national reference center in Peru.
      MATERIALS AND METHODS.: A case series study of patients who underwent heart
      transplantation between March 2010 and February 2018. RESULTS.: Sixty-one (61)
      transplanted patients with a mean age of 40.1 years (range: 9-66 years). Five
      cases (8.2%) initially diagnosed as dilated cardiomyopathy were reclassified
      after the histopathological study. The three leading causes of primary disease
      after transplantation were: idiopathic dilated cardiomyopathy (50.8%), ischemic
      cardiomyopathy (16.4%), and valvular cardiomyopathy (6.6%). The mean follow-up
      was 2.8 years. The post-transplant survival rate was 85.1% at 1 year and 82.8% at
      5 years. Moderate/severe acute cellular rejection occurred in 12 patients (21.1%)
      and antibody-mediated rejection occurred in 3 patients (5.3%). CONCLUSIONS.:
      Routine histopathological evaluation of the explanted heart is essential to
      confirm the etiology of heart failure, especially in cases clinically diagnosed
      as dilated cardiomyopathy. In addition, routine follow-up through endomyocardial
      biopsies shows that acute cellular rejection is still a frequent complication
      after a heart transplant, especially within the first year, and that antibody
      mediated rejection has a low incidence in our population.

PMID- 30183904
TI  - [Characteristics of chronic obstructive pulmonary disease due to tobacco
      consumption in pneumology patients in lima and callao].
AB  - The aim of the study was to describe the clinical characteristics of patients
      with COPD receiving treatment at the pneumology units of specialized care centers
      in Lima and Callao. A cross-sectional study was performed on 196 patients, with a
      mean age of 69 years, interquartile range of 63-75 years. Of these patients,
      31.1% was classified in the GOLD 1/ mild group (FEV1 >=80%); 41.8% in the GOLD
      2/moderate group (50%<=FEV1<80%); 22.5% in the GOLD 3/severe group
      (30%<=FEV1<50%), and 4.6% in the GOLD 4/very severe group (FEV1 <30%). A 93.9% of
      patients used some type of medication for COPD. The most-frequently used therapy
      was the combination of long-acting beta agonists and inhaled corticosteroids
      (LABA/ICS) (31.1%). A preliminary characterization has been obtained for COPD
      patients treated in these centers, but it is essential to complement these
      findings with longitudinal studies.

PMID- 30183905
TI  - [Mycobacteria identification in solid culture by inverted phase microscopy and
      ziehl-neelsen stain].
AB  - With the aim of identifying morphological differences in colonies of different
      species of mycobacteria by means of inverted phase microscopy, nine species of
      high-prevalence pathogenic mycobacteria were seeded in 7H11 solid medium and were
      observed for up to 21 days. Additionally, Ziehl-Neelsen (ZN) stains were carried
      out for each one of them. No morphological variations were identified among the
      species grown on solid medium; however, it was identified that all are able to
      form cords in solid medium in an early stage of growth, being corroborated by the
      Ziehl-Neelsen stain in Mycobacterium tuberculosis. so techniques based on
      detecting M. tuberculosis depending on the identification of the cords should be
      taken with caution so as not to generate a bad diagnosis, so microbiological
      characteristics could also be established as a minimum time to detect growth,
      temperature of growth and bacillary characteristics based on the Ziehl-Neelsen
      stain for each species studied.

PMID- 30183906
TI  - [Lyme disease in Peru. A clinical and epidemiological review].
AB  - This is a critical and organized review of all the available and updated
      information on Lyme disease and Borrelia infection in Peru. Several studies of
      positive serology to Borrelia burgdorferi and several cases of Lyme disease have
      been reported in Peru in the last two decades. New information suggests that new
      species of Borrelia burgdorferi sensu lato do exist in South America, and
      possibly in Peru. Future genetic and microbiology studies in this part of the
      continent, not only in cases with an indeterminate Western blot but in vectors
      and possible reservoirs as well, are necessary to measure the extent and clinical
      implications of these new Borrelia species.

PMID- 30183907
TI  - [Water quality and sustainable development].
AB  - Water quality is an essential ecological value for health and economic growth. In
      Peru, due to its mineralogical nature by the presence of the Andean Mountain
      System and its economy dependent on the extraction of minerals, conditions exist
      for the dispersion of chemical contaminants, especially metals, which can reach
      the drinking water, causing a generalized exposure of the population to a chronic
      risk that is already becoming unmanageable. Pollution of watersheds exposes
      people to cadmium in the northern part of the country, to lead in the central
      regions, and to arsenic in the south. Physical-chemical treatment is becoming
      increasingly expensive for drinking water companies. In this context, the socio
      environmental conflicts have evidence through the presence of heavy metals in the
      blood that is enough to generate adverse climates for the economy and delay in
      investments, resulting in a vicious circle that is difficult to resolve. The
      analysis of the two causes: mineralogical nature and mining extraction, must be
      deepened to achieve an adequate solution that prioritizes people's health, but
      also promotes investments for economic growth. The objective of this review is to
      motivate Health Authorities to address the problem and to develop risk
      communication strategies so that the problem can be addressed in a cost-effective
      manner through health education, while at the same time continuing to make
      progress in the development of more eco-efficient mining technologies.

PMID- 30183909
TI  - [Neonate with Ventriculitis caused by Empedobacter Brevis: Report of a case in
      Peru].
AB  - Infections caused by rare micro-organisms are the subject of research, as
      researchers are encouraged to find the necessary health measures to prevent and
      treat the disease, as well as the search for new insights into human-microbial
      interactions. This report describes the case of a newborn boy diagnosed with
      hydrocephalus and myelomeningocele who developed ventriculitis and sepsis from
      resistant Empedobacter brevis. This case highlights the unexpected identification
      of this bacterium in the cerebrospinal fluid and its multi-resistant pattern,
      which was crucial for proper therapeutic management. This bacterium shows a
      mixture of different etiologies in the analysis of cerebrospinal fluid.

PMID- 30183908
TI  - [Methodological perspectives of public health research. A brief look].
AB  - Research allows for the strengthening of disciplines, particularly those that
      draw on information from various specialties, such as public health. The
      objective of this report is to provide consolidated methodological perspectives
      to enrich public health as a science. The review highlights three key elements:
      the type of investigative approach, the evidence and competence approaches in the
      methodological context of the inquiry into collective health. It is concluded
      that the systematic, specific knowledge, integrated to the context and obtained
      in attention to the circumstances of the investigation, the object of study and
      the institutional location, contribute with the strengthening of public health as
      a multidisciplinary science, directly involved, for its competence and based on
      the evidence, in the decision making in matters of health by the State in areas
      as important as needs, services and health systems.

PMID- 30183910
TI  - [Cardiac Hydatid Cyst in a Child: A Case Report].
AB  - Echinococcosis is a parasitic infection caused by Echinococcus granulosus, which,
      in its cystic state, forms the socalled hydatid cyst. It presents important
      morbidity, with possible sequelae related to the location, and high costs due to
      surgical and prolonged pharmacological treatment. The liver and the lung are the
      most common anatomical locations, and much rarer are the kidney, spleen, brain,
      and heart, where the latter represents 0.5 to 2% of total cases. Peru is an
      endemic country of this anthropozoonosis and mainly records cases in the central
      highlands (95%). This paper presents the case of a 10-year-old girl, diagnosed
      with this disease, CE1 ultrasound classification, clinical group 1 (confirmed by
      pathological anatomy) with specific surgical and pharmacological treatment
      (albendazole) afterward. The patient recovered satisfactorily from the surgery
      and was discharged at 16 days, without complications.

PMID- 30183911
TI  - [Inadequate Free Residual Chlorine Concentrations in Water of Homes in Lima
      Metropolitana, 2016].

PMID- 30183912
TI  - [Characteristics of Tuberculosis Disease in Health Science Students in Peru].

PMID- 30183913
TI  - [Validity of peruvian studies on stress and burnout].

PMID- 30183914
TI  - [Duplicate Publication Of A Case Report].

PMID- 30183915
TI  - [Traffic regulation and environmental pollution by particulate material (2.5 and
      10), sulfur dioxide, and nitrogen dioxide in Metropolitan Lima, Peru].
AB  - OBJECTIVE.: To assess the change in environmental levels of PM2.5, PM10, SO2, and
      NO2, after the application of a traffic regulation plan in Abancay Avenue between
      the years 2013-2015 vs. to 2007-2009, and comparing it against two other avenues,
      in which no traffic regulation was implemented: Guillermo de La Fuente Avenue in
      the district of Comas and Cesar Vallejo Avenue in El Agustino. MATERIALS AND
      METHODS.: Environmental data were collected by three air monitors from the
      Ministry of Health's Environmental Health and Food Safety General Directorate
      (Direccion General de Salud Ambiental e Inocuidad Alimentaria) that are part of
      the Air Quality Surveillance network of the city of Lima. The beta coefficient of
      the linear regression allowed to assess change in the concentration of each
      pollutant. RESULTS.: The traffic regulation plan of Abancay Av. reduced the
      levels of PM2.5 by 62%; 55% for PM10 levels; 65% for the NO2 levels, and 82% for
      the SO2 levels. In the other two avenues assess, this reduction was not observed.
      A significant reduction in PM2.5 (beta: -53.11 MUg/m3; 95% CI: -63.92 to -42.30),
      PM10 (beta: -47.99 MUg/m3; 95% CI: -62.61 to -33.37), NO2 (beta: -41.71 MUg/m3;
      95% CI: -48.18 to -35.23), and SO2 (beta: -28.59 MUg/m3; 95% CI: -35.23 to 
      21.95) was observed in Abancay Av., with respect to the other two avenues, after
      the traffic regulation plan was implemented. CONCLUSIONS.: Traffic regulation can
      contribute to the continuous reduction of different air pollutants. The expansion
      of this measure could improve air quality and the health status of the residents
      of Lima.

PMID- 30183916
TI  - [Perceptions regarding intercultural education in the doctor-immigrant patient
      relationship in chilean doctors].
AB  - OBJECTIVE.: To delve into the doctors' perceptions about training for
      intercultural practice in the doctor-immigrant patient (DPR) relationship in
      Chile. MATERIALS AND METHODS.: A qualitative study was carried out in communes of
      the metropolitan region (RM) through in-depth interviews with doctors. The
      inclusion criteria for the sample were: to be a doctor, to have a formal work
      relationship in a public health center, and to have had contact with the
      international migrant population living in each commune. The final sample
      consisted of 13 doctors; information saturation criteria were considered.
      RESULTS.: There is a greater tension related to intercultural coexistence,
      favored by the cultural, language, and prejudice barrier. The absence of records
      about the patients' national origin contributes to these perspectives. The
      findings show the lack of training geared towards understanding and caring for a
      diverse population on a daily basis; as well as the need to get familiar with the
      immigration phenomenon going on in Chile and the current Latin American
      diversity. CONCLUSIONS.: New challenges to medical training in light of the
      growing migrant population in Chile are discussed here. The emergence of
      interculturality in medical training raises critical aspects that are articulated
      with healthcare intercultural and human rights approach.

PMID- 30183917
TI  - [Identification and structural determination of a sesquiterpene of Tessaria
      integrifolia Ruiz & Pav. leaves and evaluation of its leishmanicidal activity].
AB  - OBJECTIVE. : To identify and determine the phytoconstituent structure of Tessaria
      integrifolia Ruiz & Pav. leaves with leishmanicidal activity. MATERIALS AND
      METHODS.: Fluid extract of leaves was prepared, concentrated to soft extract, and
      used to evaluate leishmanicidal activity in Mesocricetus auratus with
      experimental leishmaniasis, at the dose of 250 mg/kg of soft extract by
      intramuscular route for 15 days. Extract was fractionated in 45 cm column
      chromatography with a 2.5 cm diameter, containing G-60 silica gel, and 70-230
      mesh (Sigma-Aldrich(r)). Nine fractions were obtained and assessed on macrophages
      infected with Leishmania sp to determine the active fraction and isolate the
      active compound, by separation, purification, and crystallization, analyzed by
      nuclear magnetic resonance (NMR) of 1H, 13C, and liquid chromatography coupled to
      mass spectroscopy (LC/ MS). RESULTS.: Fluid extract from the leaves of T.
      integrifolia presents leishmanicidal activity in M. auratus. Fraction F8 is
      active on infected macrophages at a dose of 14 MUg/mL. An eudesman type
      sesquiterpene ((4aS, 5R, 6R, 8aR) -6-hydroxy-5, 8a-dimethyl-3- (1
      methylethylidene) octahydronaphthalen-2 (1H) -one) was identified, by RMN 1 H,
      13C, and LC / MS analysis. CONCLUSIONS. : Fluid extract of leaves of Tessaria
      integrifolia Ruiz & Pav. presents leishmanicidal activity on Mesocricetus auratus
      with experimental leishmaniasis. Fraction F8 presents leishmanicidal activity on
      infected macrophages at a dose of 14 MUg/mL. An eudesman type sesquiterpene was
      identified, according to 1 H, 13C, and LC / MS NMR analysis.

PMID- 30183918
TI  - [Acceptability of purified fish-protein powder in pre-school and school age
      children].
AB  - OBJECTIVE.: To determine the acceptability of purified fish protein (FPi) in
      cereal and pseudocereal-based drinks. MATERIALS AND METHODS.: The study was
      carried out at Centro de Desarrollo Integral Familiar "Ano Nuevo" belonging to
      the INABIF Program in the district of Comas in Lima. FPi (0-4 g per serving) was
      administered daily for 3 months mixed with cereal and pseudocereal-based drinks.
      The acceptability of FPi was measured by direct weighing in children under 6
      years of age and by the hedonic facial scale in school-age children. RESULTS.:
      One hundred and fifty-eight (158) participants were enrolled and 4,211 breakfasts
      were served. The caloric intake of the cereal and pseudocereal drinks, after
      adding the FPi, ranged between 117 and 140 Kcal, and protein intake ranged
      between 3.4 g and 5.4 g per serving. The acceptability of drinks supplemented
      with FPi in children older than 6 years of age (the 2 highest scores together)
      ranged from 55% to 74% for oats, around 47% for quinoa and 40% to 58% for
      "kiwicha" (amaranth). Whereas 90% of children under 6 consumed more than 70% of
      the drinks offered. CONCLUSIONS.: We found a good acceptability of FPi in cereal
      and pseudocereal beverages in children under 6 years of age. FPi is an
      alternative to improve the consumption of animal protein in the nutrition of
      children, especially in pre-schoolers.

PMID- 30183919
TI  - [Anemia as a prognostic factor in cancer patients].
AB  - OBJECTIVE.: To determine the frequency and prognostic value of anemia in cancer
      patients receiving care at the National Institute of Neoplastic Diseases
      (Instituto Nacional de Enfermedades Neoplasicas - INEN) between January and April
      of 2010. MATERIALS AND METHODS.: Anemia was considered for men with hemoglobin
      levels at <13 g/dL; and for women, at <12 g/dL. Associations between qualitative
      features were assessed with a Chi-square test. Kaplan-Meier estimator was used
      for the analysis of the survival curves, and differences between the curves were
      performed with the log-rank test. RESULTS.: 772 patients were included; 584
      (75.7%) had solid tumors and 188 (24.3%) had hematologic malignancies. Anemia was
      diagnosed in 359 patients (46.5%); hematologic malignancies in 127 patients
      (67.6%); and solid neoplasms in 235 (40.2%). Hematologic malignancies with the
      highest frequency of anemia were chronic myeloid leukemia, acute leukemias, and
      multiple myeloma (100%, 92.5% and 60%, respectively); and were cancer of
      gastrointestinal, gynecological, and urological origin were in the group of solid
      neoplasms (62%, 52.1% and 45%, respectively). Two hundred and four (204) patients
      (26.4%) were transfused. In 762 patients, a significant difference in overall
      survival was found between groups with and without anemia, estimated at 5 years
      in 62% and 47% respectively (p <0.001). In the solid tumor subgroup (p = 0.002),
      and the hematological malignancies subgroup (p = 0.007), such association was
      also found. CONCLUSIONS.: Anemia is common in cancer patients, and its presence
      determines an independent prognostic factor in overall survival.

PMID- 30183920
TI  - [Identification of carbapenem-resistant genes in enterobacteria from peruvian
      hospitals, 2013-2017].
AB  - The global spread of carbapenemases is a significant public health concern. The
      aim of this report is to describe the presence of KPC-type carbapenem-resistant
      genes and enterobacteria isolated in 12 hospitals and forwarded to the Peruvian
      National Institute of Health's National Infection Reference Laboratory during the
      period between 2013 and 2017. The strains were identified by conventional
      methods; antimicrobial resistance was determined by phenotypic and biochemical
      methods. The presence of resistant genes was detected by conventional PCR. Eighty
      three (83) strains harboring carbapenemases were identified: 26 (31.3%) carrying
      the blaKPC gene, 56 (67.5%) the blaNDM gene, and one strain (1.2%) with the
      blaIMP gene. This is the first report that shows the circulating carbapenemases
      genes in Hospitals in Peru of cases submitted for their confirmation to the
      National Reference Laboratory, so it is necessary to improve the surveillance to
      better understand their situation in our country.

PMID- 30183921
TI  - [Characteristics of acute lymphoblastic leukemia and febrile neutropenia in
      children and adolescents cared for in a hospital in Guayaquil, Ecuador].
AB  - With the objective of performing a clinical characterization of children and
      adolescents with acute lymphoblastic leukemia and febrile neutropenia in a
      hospital in Ecuador, a case series study was carried out, which involved
      reviewing the clinical records of patients receiving care at "Hospital de la
      Sociedad de Lucha Contra el Cancer" in Guayaquil between January 2014 and April
      2016. Out of the 101 patients, 51.5% were female; mean age was 5.5+/-2.1 years
      old; 72.3% were at high risk for invasive bacterial infection; the most common
      infections were respiratory with 47.5%; 18.8% of bacteria isolated in blood
      cultures were Gram-positive. Finally, 25.7% of patients died, with chemotherapy
      resistance as one of the associated factors.

PMID- 30183922
TI  - [International migration and health: the contribution of migration social
      theories to public health decisions].
AB  - Evidence demonstrates the high levels of vulnerability that surround the current
      migration phenomenon. These conditions are crucial to health systems worldwide,
      as they are directly linked to worsening health status and quality of life.
      However, the study of the connection between the migration process and health
      remains insufficient, especially with regard to how international migration
      influences public health decision-making. In the Latin American and Caribbean
      region, there are initiatives to provide health services to international
      migrants, but they are still far from guaranteeing the fundamental health rights
      of those who migrate. This article aims to develop a critical discussion of the
      main social theories on migration, and its contribution to public health decision
      making (push-pull theory, globalization theory, causal accumulation theory, and
      transnationalism). An academic narrative review was carried out until April 2017,
      the results of which indicate that institutional, state, and local public health
      action is essential to guarantee the health rights of the migrant population in
      the face of the precarious situation surrounding the migration phenomenon. It is
      hoped that this document will be a contribution to current knowledge in Latin
      America, both for teaching and for practice and research in public health.

PMID- 30183923
TI  - [Considerations about management of water resources and public health in Peru].
AB  - This article is presented as an exercise to reflect on the current Peruvian
      situation in terms of access to safe water and its consequences on health.
      Additionally, it aims at pondering on the challenges that the country must face
      in order to achieve water security. It also proposes some guidelines to direct us
      toward water security in Peru. This article is not intended to be a source of
      reference of statistical data on the availability and access to water resources
      in Peru.

PMID- 30183924
TI  - [Infectious diseases related to water in Peru].
AB  - The growth of the world population has increased the demand for water. On the
      other hand, climate change shows us that the water sources that were previously
      safe are not anymore. There are inequalities between urban and rural areas, thus
      96% of the urban world population uses drinking water sources compared to 84% of
      the rural population, while 82% of the urban population versus 51% of the rural
      population use sanitation facilities. In Peru, 80.4% of homes are supplied with
      water through a public network. In the urban area, this service covers 83.2%;
      while in the rural area 71.3% of homes have a toilet service connected to the
      public network. All the above conditions the presence of water-related infectious
      diseases, such as diarrhea, malaria, dengue, leptospirosis, viral hepatitis A,
      and E, whose classification is shown in this article. In the world, diarrhea is
      the third cause of death among children under five years of age and more than
      340,000 children under the age of five die from diarrheal diseases due to poor
      sanitation. One of the goals of the SDGs is related to universal access drinking
      water, sanitation and hygiene, which cannot be achieved without due attention to
      the inequalities in access observed between different groups, avoiding the
      consequences of these deficiencies both in our country and in the world.

PMID- 30183925
TI  - [Public health interventions: conceptual basis for the determination of
      objectives and evaluation].
AB  - This article aims to disseminate relevant concepts in the design of health
      interventions. Taking into account that the epidemiological evidence and the
      strength of the available instruments or technological control composition are
      fundamental for the determination of a scale of public health objectives:
      extinction, eradication, elimination, control or reduction of levels of exposure
      or control of natural transmission, reduction or prevention of the occurrence of
      epidemics, limitation of damage and reduction of mortality. The limiting factor
      for achieving these objectives must be given by the epidemiology of the disease,
      which may be determined by inaccessibility or exceptional patterns of
      transmission, operational difficulties, and insufficient means, but not by the
      inapplicability of existing knowledge.

PMID- 30183926
TI  - [Breast tuberculosis: a case report].
AB  - We present a case of mastitis in a 45-year-old woman with no history of infection
      in other areas of the body, with unspecific clinical picture, imaging studies,
      and bacilloscopy. However, histological samples obtained by aspiration showed
      giant epithelial cells, necrosis, and granulomatous formations, which justified a
      clinical inclination toward tuberculosis. In the absence of confirmatory evidence
      of any lesions in other tissues, the existence of mastitis of torpid evolution is
      a clinical indication to suspect mammary tuberculosis, since the characteristics
      of the process usually lead to erroneous diagnoses with other breast tumors such
      as cancer. Tuberculosis in the breast is a rare disease with a difficult
      diagnosis due to the low clinical and microbiological evidence and the lack of
      specificity of the imaging results, so the suspicion of its real diagnostic
      possibility is a fundamental condition for its determination, even when the
      causal agent is not confirmed.

PMID- 30183927
TI  - [Microscopic visualization of mycobacteria cords in 7H11 medium and
      differentiation through Ziehl-Neelsen stain].

PMID- 30183928
TI  - [First evidence of Aedes aegypti in the Arequipa Region, Peru 2016].

PMID- 30183929
TI  - [Socio-geographic inequalities in maternal mortality in Peru: 2001-2015].

PMID- 30183930
TI  - [Incentives for scientific publication in peruvian universities that have medical
      schools, 2017].

PMID- 30183931
TI  - [Family life cycle and lifestyles: arterial hypertension and diabetes mellitus
      II].
AB  - OBJECTIVE : To determine the influence of the family life trajectory on the
      appropriation of lifestyles of people diagnosed with arterial hypertension or
      diabetes mellitus II in Cali, Colombia. MATERIALS AND METHODS: Qualitative,
      exploratory and comparative study in the field of medical sociology. A semi
      structured interview was applied. RESULTS : The family life cycle is a dynamic
      and changing process that encompasses the origin of the life cycle up to the
      present moment. It involves behaviors, practices, interests, perceptions and
      interaction relations. This process is possible because of the interaction of the
      subjects with the social context that influences their actions. CONCLUSIONS :
      Lifestyles are not "simple" individual practices that shape a certain way of
      living, but complex and dynamic social constructs that are permeated by
      interaction, particularly, family relationships, which make an important
      contribution to this process. The way in which subjects live their health-disease
      process is influenced by their behavior, which allows social development based on
      life cycles, and affected by the social class to which they belong. This
      configuration serves as the basis to understand the reasons why apprehending or
      not the practices and instructions given in hypertension and diabetes control
      programs is possible.

PMID- 30183932
TI  - [Determinants of psychomotor performance in schoolchildren from Barranquilla,
      Colombia].
AB  - OBJECTIVE : To establish the prevalence of the psychomotor profile in children
      aged four to eight years attending the schools of the North Historical Center of
      Barranquilla, Colombia. METHOD : A cross-sectional descriptive study was
      conducted in 755 students from public and private schools aged between 4 and 8
      years. The motor profile was measured by Da Fonseca Psychomotor Battery. RESULTS
      : An increased risk for apraxic-dyspraxic performance of the global praxis
      subfactor was observed in schoolchildren aged four to five years [OR 4.8; 95 %
      CI; 3.3-7.1] who study in public schools [OR 4.4; 95 % CI; 2.7-7.3], in those
      classified in the socioeconomic in strata 1, 2 and 3 [OR 2.4; 95 % CI; 1.5-3.9],
      and in those with an increased weight [OR 2; 95 % CI; 1.2-3.3]. The highest risk
      for apraxic-dyspraxic performance correlated to public school students [OR 1.9;
      95% CI; 1.3-2.8] aged between four and five [OR 3.7; 95 % CI; 2.7-5.3]. The
      apraxic-dyspraxic performance in the structuring of the temporal space subfactor
      was higher in girls [OR 1.6; 95 % CI; 1.1- 2.2], in schoolchildren aged four to
      five [OR 4.8; 95 % CI; 3.3-7.1], in students of public schools [OR 1.9; 95 % CI;
      2.7- 5.3], and in children classified in the socioeconomic strata 1, 2 and 3 [OR
      1.6; 95 % CI; 1.1-2.7]. CONCLUSIONS : Determinants such as studying in public
      schools, nutritional status, gender and socioeconomic stratum are related to
      motor performance in students.

PMID- 30183933
TI  - [Food intake and its relation with socioeconomic factors in an older adults
      group].
AB  - OBJECTIVE : To describe food intake and establish the correlation between some
      socioeconomic factors in a group of senior adults. MATERIALS AND METHODS :
      Descriptive, cross-sectional study with 178 adults, >=60 years old, who attended
      a dental consultation at Universidad de Antioquia between September 2014 and
      February 2015. Measurements for socio-demographic variables, frequency of food
      intake and food safety scale were obtained. The Chi-squared test was used to
      determine the association between food intake and socioeconomic variables. The
      categorical principal components analysis was used to determine feeding patterns.
      RESULTS : About 50 % of the sample consumed dairy between one and three times a
      day, and meat, fruits and vegetables from one to two times. 74.7 % consumed
      cereals, bananas and tubers more than four times a day, which contrasts with dry
      grains and monounsaturated fat, whose frequency was less than once per day. Dairy
      and fruit intake had a significant association (p<0.05) with the following
      variables: economic income, stratum and food safety. Three dietary patterns known
      as "traditional varied diet", "unvaried" and "eating out of home" were
      identified, which explained the phenomenon in 12.8 %, 9.9 % and 8.4 %,
      respectively. CONCLUSION : The daily consumption of food groups in the elderly
      could be determined by the socioeconomic condition, being better in the medium
      stratum, who live in safe households and receive incomes. The pattern that
      explained the variability of consumption in greater proportion was the
      traditional varied diet.

PMID- 30183934
TI  - [Microbiological evaluation of artisan coastal cheese and hygienic-locative
      evaluation of small shops in Cordoba, Colombia].
AB  - OBJECTIVE : To perform a microbiological analysis of the artisan cheese consumed
      in the county seats of the Cordoba department, and to evaluate the hygienic
      locative conditions of small shops that favor contamination. METHODS : An
      exploratory and descriptive research was carried out in 120 small shops
      registered in the Departmental Health Secretariat of the 28 municipalities of
      Cordoba-Colombia during 2012-2013. The organoleptic characteristics of 360
      samples were evaluated and, the presence of total coliforms, fecal coliforms,
      coagulase-positive sta-phylococci and fungi was determined through a
      microbiological analysis. The results were analyzed using univariate and
      bivariate statistics with their respective association measures according to the
      nature of each variable (EPI-INFO V. 6.04(r) Program). RESULTS : The
      microbiological assessment of 360 samples showed contamination with values not
      suitable for consumption equivalent to: total coliforms (97.5 %), fecal coliforms
      (88.9 %), coagulase-positive staphylococci (41.4 %), mold (40.4 %) and yeast
      (96.1 %). Significant factors such as contamination, inadequate cleaning of
      floors, walls and ceilings, exposure conditions, ventilation, lighting and
      improper handling of the product were observed. CONCLUSION : The significant
      microbiological load observed in the examined cheeses and their assessment as
      unfit for human consumption reflect the hygienic deficiencies in the handling of
      the product, which, along with locative defects in the places where they are
      marketed, endangers the health of the consumer.

PMID- 30183935
TI  - [Levels of serum cholinesterase in coffee growers from the Caldas Department,
      Colombia].
AB  - OBJECTIVE: To determine the levels of serum cholinesterase in coffee growers from
      the Caldas department and its association with demographic and labor factors.
      METHODOLOGY : A descriptive study was carried out in a sample of 1 098 farmers
      from the Upper East and South Center of the Caldas department, through a survey
      that analyzed characteristics such as sociodemographic, labor, and clinical
      conditions, as well as cholinesterase levels, determined by Ellman's method.
      RESULTS : Regarding the occupational aspect, 90.8 % of farmers reported a risk of
      direct exposure to pesticides. 3.8 % of the analytical determinations of
      cholinesterase were abnormal, which was related to the fact that 75.6 % of the
      farmers themselves prepare the mixture of the insecticide, 22.2 % spread the
      insecticide over their crops more than twice a week, and 37.8 % do not wear
      protective clothing during the fumigation. The last fumigation was within the
      range of one to ten days, revealing that the shorter the time of application of
      the insecticide, the greater the inhibition of the enzyme. The most frequent
      pesticides were organophosphates (58.6 %). CONCLUSIONS : Controlling pesticide
      exposure is difficult because most workers are self-employed. It is necessary to
      strengthen training programs and awareness campaigns regarding the effect of
      pesticides on health, as well as health and safety measures at the workplace. Low
      levels of serum cholinesterase indicate the absorption of a minimal amount of
      cholinesterase inhibiting insecticides.

PMID- 30183936
TI  - [Environmental health at La Chaparrala subbasin, Colombia 2015].
AB  - OBJECTIVE : To assess environmental health conditions at La Chaparrala subbasin,
      in the Andes Mountains of Colombia, during 2015. METHOD : Descriptive cross
      sectional study on sanitary and environmental conditions of the dwellings, as
      well as on immediate environment, and environmental health prejudices. A survey
      was applied to 117 families settled in the main axis of the creek. The
      physicochemical quality of the water was analyzed. RESULTS : Men were predominant
      as head of household, with an average of four people per house. 69 of the houses
      were in the urban area, while 48 were rural; the permanence was greater than 20
      years for the first, and less than five years for the second. Most of the houses
      are owned with deeds, and 75 % of them had a connection to the aqueduct and 73 %
      to the sewer. The houses in the urban area were predominantly made of tile roof
      and tile floor, while rural houses were made of mud tile and concrete floor. Both
      types of construction had adobe walls. The water from the creek complied with the
      physicochemical parameters established in the technical regulation of the sector
      for drinking water and basic sanitation, and with resolution No. 2115 of 2007.
      Non-compliance was observed in turbidity and nitrite levels, and occurrences and
      concurrences on environmental health were found. DISCUSSION : The socio
      demographic characteristics and environmental and health conditions of the
      dwellings and their surroundings are similar to those reported in Encuesta de
      Demografia y Salud 2010 (Demographic and Health Survey) and Encuesta Nacional de
      Salud 2007 (2007 National Health Survey). The creek may continue to be a source
      for human consumption with conventional treatment and environmental health
      directed to care and protect the environment, differing from the concept of World
      Health Organization (WHO).

PMID- 30183937
TI  - [Perinatal hypoxia at Hospital Mederi in Bogota: behavior in the period 2007
      2011].
AB  - OBJECTIVE : To identify maternal, fetal and neonatal risk factors associated with
      perinatal hypoxia in neonates at Hospital Universitario Mayor Mederi (HUM Mederi)
      from 2007 to 2011. METHODOLOGY : In the period 2007-2011, 8 837 children were
      born in HUM Mederi. Only the cases that presented with perinatal asphyxia (PA),
      according to the American Congress of Obstetricians and Gynecologists (ACOG), or
      another respiratory distress (RD) diagnosis were considered for this analysis,
      based on the computer records of the Neonatology Service in HUM Mederi. Maternal,
      fetal and neonatal risk factors were analyzed. Data were shown according to the
      number of newborns in each group and their percentage. RESULTS : The overall
      mortality rate was 10.7. The lowest values were found in 2010 and 2011 (3.3 and
      1.8, respectively). Gestational diabetes, hypertension, chorioamnionitis and
      placenta previa were more frequent in the RD group, whereas hypoglycemia, sepsis,
      hypotonia and hypoactivity among neurological alterations were more common in the
      PA group. Correspondence between neurological alterations and Apgar Test was low
      in the cases diagnosed with PA. CONCLUSIONS : The mortality rate was very low
      compared to regional and local levels, and more infants presented with moderate
      perinatal asphyxia. These results coincide with literature reports. The high
      number of preterm births with DR emphasizes the importance of controlling the
      implementation of actions to reduce the risk factors associated with this
      condition.

PMID- 30183938
TI  - [Quality of life related to health in the Colombian population: how do Colombians
      perceive their health condition?]
AB  - OBJECTIVE : To determine the perception about quality of life related to health
      in the adult population of Colombia. METHODS: Population-based survey applied on
      a representative sample of the Colombian rural and urban population, aged 18
      years or more. Quality of life related to health was measured using the generic
      EQ5D instrument and the analogue visual scale as part of the fourth National
      Mental Health Survey. Estimates were accompanied by 95 % confidence intervals and
      were adjusted by the sampling design. RESULTS : 10 867 people aged 18 years or
      older completed the measurement. 69.7 % (CI95 %; 66.9-68.9) of the population
      reported being "completely healthy". Most of the population rated their health
      condition above 80 points. The presence of "moderate pain or discomfort",
      followed by being "moderately distressed or depressed" were the most frequent
      alterations. Young adults tend to perceive their health better than older adults.
      There is no difference in the perception of health between regions of the
      country. CONCLUSIONS : Quality of life related to health in the Colombian
      population is greater than 80 points on a scale of 1 to 100. Alterations such as
      angst and depression and the perception of pain were the most frequently reported
      by Colombians. Poverty and a low level of education are determinants of the
      perception of Colombians regarding their quality of life related to health.

PMID- 30183939
TI  - [Prevalence of musculoskeletal injuries in racing skaters in Villavicencio,
      Colombia].
AB  - OBJECTIVE : To determine the prevalence of musculoskeletal injuries and their
      relation to different presentation variables in inline speed skaters by age
      categories, between 8 and 23 years of age, from Villavicencio, Colombia. METHODS:
      An observational cross-sectional or prevalence analytical study was developed by
      applying an information collection instrument that was designed and validated
      qualitatively and quantitatively. The instrument included variables associated
      with the presentation of lesions organized in five domains. The information
      collected was analyzed with descriptive statistics. RESULTS : 66.7 % of the
      population studied were females, 39 % of skaters had between five and six years
      of sporting experience, and were in the transition category. Nine out of ten
      athletes trained more than five days a week, and the same proportion did three to
      five hours of daily training. The prevalence of musculoskeletal injuries was 53.7
      % in the total population studied; 29.6 % had between one and two injuries, and
      5.6% of injured skaters had between nine and ten injuries. CONCLUSIONS: Most of
      musculoskeletal injuries were related to the younger age categories, in
      precompetitive and specific preparation periods. The lower limbs were the most
      affected, to a greater extent, by bony and muscular lesions.

PMID- 30183940
TI  - [Detection of Trypanosoma cruzi antibodies in blood donors from Caqueta-Colombia,
      1995-2010].
AB  - OBJECTIVE : The aim of this article is an epidemiology characterize of screening
      positive samples and confirmed cases to Trypanosoma cruzi in blood donor at
      Caqueta, Colombia from 1995 to 2010. MATERIAL AND METHODS : This study was a
      descriptive and retrospective analysis where the information was obtained from
      blood bank and Public Health Departmental Laboratory of Caqueta. These were
      collected on standardized form in Microsoft Excel(r) with specific variables.
      Afterward, they were organized and information was added from Colombian data
      bases as FOSYGA and Registraduria Nacional. Both, multiple correspondence
      analysis and univariate and bivariate descriptive statistics were used to analyse
      the data on mathematic program R(r) and Microsoft Excel(r), respectively. RESULTS
      : From a total of 42.516 blood donations, 261 were seropositive and 92 were
      confirmed cases to T. cruzi. CONCLUSION: Characterize the confirmed cases of T.
      cruzi and identify their current location through the looking for the information
      and its comparation with the national data bases is an important sources to find
      these confirmed cases in order to give a relevant clinical procedure by the
      competent authorities.

PMID- 30183941
TI  - [Quality of life related to health in the mining population of Boyaca].
AB  - OBJECTIVE : To evaluate the perception of quality of life in inhabitants of
      mineral mining areas of mineral coal and agricultural areas. MATERIALS AND
      METHODS : Descriptive cross-sectional study of 229 individuals living in coal
      mining municipalities (n=151) and municipalities with agricultural activities
      (n=78). Those who answered SF36 survey and socio-demographic test. RESULTS : It
      was found that the perception of the health-related quality of life is lower in
      the inhabitants of the area of coal exploitation compared to the inhabitants of
      agricultural zone only with statistical difference in the general perception of
      the scale and with no difference pro each one of the scales. DISCUSSION :
      Pollution generated in coal mining areas has an impact on the health of people
      and their perception of quality of life. The evidence is weak in showing no
      statistically significant differences by area in each subscale and was only
      demonstrated in general perception.

PMID- 30183942
TI  - [Experiences in construction, dissemination and use of the health situation
      analysis in Colombia 2016].
AB  - OBJETIVE : The Health Situation Analysis (ASIS in Spanish) is a methodology that
      has been implemented recently in Colombia. This study aims at understanding the
      experience of building, disseminating and using ASIS for decision-making in some
      territorial entities. METHODS : Semistructured interviews were applied to
      officials of the departmental health entities. The information was analyzed
      according to a set of categories previously established. RESULTS : The
      territorial entities implement ASIS by incorporating the Social Determinants of
      Health approach; however, the technical, economic and human capacities for the
      elaboration of this type of analysis are not equitable. Intersectoral and social
      participation is still weak and the results do not guide the decision making at
      territorial level yet. CONCLUSIONS : The ASIS methodology seeks to position
      itself as one of the official mechanisms to generate evidence that guides health
      policy and decision making at national, regional and local levels. There are
      economic, institutional and political challenges for its consolidation as a
      useful strategy in health planning. ASIS is a methodology of great relevance for
      the territorial entities and its implementation should be further strengthened.

PMID- 30183943
TI  - [Adolescent pregnancy in Mexico: a public health issue].
AB  - Adolescent pregnancy is considered a public health issue by the World Health
      Organization (WHO) because of the biopsychosocial impact that it has on the
      health of the mother and the child. Complications during pregnancy and childbirth
      are the leading cause of death for adolescents in most countries. The lack of
      health guidance and education is a determining factor for the high number of
      preterm pregnancies. This paper reviews and analyzes this public health issue
      considering demographic and reproductive aspects, the institutional programs that
      have been implemented for its prevention, and its characteristics, risk factors,
      causes and consequences. Furthermore, it presents a description of the dimensions
      of adolescent pregnancy, in other words, cultural, psychological, social and
      educational aspects. Regarding education, different interventions focused on
      increasing knowledge in the prevention of pregnancy at this age and field of
      application, and that have been applied to adolescents, are reviewed.

PMID- 30183944
TI  - [Public Health in Colombian Zoos. A challenge for Veterinary Medicine].
AB  - This reflection aims to analyze the current status of public health management in
      zoos. In turn, it seeks to establish the importance of addressing this problem
      during the training and professional practice of veterinarians. The current
      situation of public health in Colombian zoos has weaknesses that are potentially
      correctable from both the academia and the daily practice of professionals
      directly or indirectly related. This becomes a challenge for educational
      institutions of related professions, zoos and veterinarians. Although some
      approximations have been made in this regard, information on this issue is still
      scarce.

PMID- 30183945
TI  - [Occupational exposure to formaldehyde and new table of occupational diseases].
AB  - This paper presents an update on the carcinogenic effect of formaldehyde. First,
      generalities of its chemical composition are considered, followed by the
      description of some of its uses, both in the industry and in health institutions,
      as well as an account of the risk to which the general population is exposed, in
      particular health personnel, as a result of prolonged exposure to this chemical
      component. Emphasis is placed on the concentration of formaldehyde in everyday
      life and in the workplace, while the guidelines of decree 1477 of August 5, 2014,
      issued by the Ministry of Labor of Colombia, on occupational exposure to this
      chemical are analyzed to demonstrate that this decree does not consider the
      already known carcinogenic effects of formaldehyde, widely supported by
      scientific evidence, thus leaving a void for both occupational prevention and
      labor legislation.

PMID- 30183946
TI  - [Interpretative speeches and deliberative practices: a methodological proposal
      for the formulation of public health policies in Colombia].
AB  - OBJECTIVE : To propose public health policies in local governance scenarios
      through community participation; this requires recognizing the interaction of all
      social actors through argumentative approaches. METHODS : Considering a critical
      hermeneutic approach, an argumentative rhetorical method was used to conduct a
      political formulation from a socio-centric scenario, based on a dialogue of
      knowledge between the community and local institutions, which allowed to identify
      and understand relevant social problems in health, related with early childhood
      and family. RESULTS : A comprehensive public policy was built in accordance with
      existing social health programs to intervene aspects referring to early
      childhood, childhood, adolescence and family. Solutions and their implementation
      arise from a participatory nucleus that reconciles institutional political
      interests and social needs of the local community. CONCLUSIONS : The
      argumentative approach in public policies recognizes the dialectical nucleus of
      politics by bringing the community closer to government entities through active
      citizen participation in processes of identification, implementation and
      execution of social policies.

PMID- 30183947
TI  - [The WHO model as a guideline for public health based on social determinants].
AB  - Public health has developed based on multiple approaches, including the
      guidelines of the health systems, the community or the individuals. This paper
      intends to identify the conceptual models of public health that arise after
      analyzing health or disease categories, as well as the level at which social
      response occurs: the individual or a family, biophysical and social environment;
      hygienist or preventive mode. Considering that the concept of model is not only a
      representation of reality, but an ontological position that allows to understand
      society and the State, all models are part of a theory and converge with other
      theories to create a framework of analysis. In consequence, three models of the
      health-disease process are presented. First, the Canadian model that establishes
      four determinants -lifestyle, environment, biological factors and health services
      . Second, the social determinants model of the World Health Organization (WHO)
      that establishes three determinants based on risk approach: structural,
      intermediate and proximal. Finally, the historical-social or social determination
      model, which looks for the roots of social inequalities that affect health. The
      development of the Colombia Health System has considered these health models.
      Today, the Comprehensive Health Care Policy, and its Comprehensive Health Care
      Model, bases its approach within a model of determinants established by the PAHO.

PMID- 30183948
TI  - [Thinking about the social determination of the health-disease process].
AB  - This article presents an epistemological discussion that underlies the proposal
      of social determination of the health-disease process, framing this discussion in
      the history of the current of thought known as Latin American Social Medicine,
      and analyzing the way in which this current approaches the study of health
      disease processes in contemporary societies. To this end, a brief historical
      framework is elaborated, and the epistemological implications of the concept of
      social determination of the health-disease process are analyzed. Finally, three
      examples illustrate how the ideas about determination in the concrete study of
      reality are applied.

PMID- 30183949
TI  - [Social determination of the health-disease process: a critical look from the
      epidemiology of the 21st century].
AB  - The so-called social determination is a key concept for Latin American Social
      Medicine (LASM). LASM criticizes epidemiology frequently, mainly because of its
      reductionist vision and its distance from social reality. This paper makes an
      opposite analysis, in other words, 21st century epidemiology criticizes LASM,
      using the disciplinary development in Colombia as an example. The history of
      Colombian epidemiology is reviewed, noting that it has not had sufficient
      development and that LASM tends to reject quantitative methods based on the
      epidemiological practices used four decades ago. Additionally, some developments
      of the quantitative methods used in epidemiology are reviewed, explaining that
      many of the limitations indicated by LASM have been overcome. In conclusion, LASM
      uses social determination as part of its leftist political platform; however,
      current quantitative methods and the 21st century theoretical developments in
      epidemiology show a pragmatic superiority, useful for solving current public
      health issues.

PMID- 30183950
TI  - [Causal inference in epidemiology].
AB  - This essay makes a brief account of the historical development of epidemiology as
      a fundamental element for understanding the development of thought and causality
      models. Subsequently, the theoretical foundations that support the identification
      of causal relationships and the available models and methods of analysis are
      exposed, providing some examples of their application. Finally, the strengths and
      limitations of this epidemiological analysis during the identification of causal
      relationships are presented.

PMID- 30183951
TI  - [Epidemiology, knowledge and practices: a critical analysis].
AB  - If research companies need to permanently review their theoretical foundations
      and objects of study, evidently epidemiology should also consider these demands
      to pursue a transdisciplinary dialogue, as required by the study of the Health
      Disease process. This dialogue should begin with a critique of its theoretical
      and methodological assumptions. Here, we discuss the concept of causality in
      epidemiology, exploring the "notions system" that has served as an original
      matrix for knowledge and practice. We analyze its close links with clinical
      knowledge, its dominant empirical-analytical orientation with a particular view
      of "the social", and finally, we present some critiques of the casual-inferential
      model, which is key in contemporary epidemiology.

PMID- 30183952
TI  - [Impact of oral health on the quality of life of pregnant woman].
AB  - OBJECTIVE: To identify the factors that determine quality of life related to oral
      health (OHIP-14) in a population of pregnant women. METHODS: This study included
      ninety pregnant women, 45 immigrants and 45 from Spain. Participants completed
      the Oral Health Impact Profile questionnaire (OHIP-14) -Spanish version- and the
      DMFT index (decayed, missing, and filled teeth) was explored during the second
      trimester of pregnancy. A bivariate and multivariate analytical study was
      performed. RESULTS: The average age of immigrant participants was 30.2, and of
      Spanish women 34.4. The mean OHIP-14 score was 5.83+/-6.57 (8.15 in the immigrant
      group and 3.51 in the Spanish group), showing a statistically significant
      difference (p=0.001). The highest OHIP-14 scores were related to pain (110),
      followed by psychological distress (81). Considering the median value in the OHIP
      14 score as a cut-off (>=3), the odds ratio for oral health that interferes with
      quality of life was 3.294, and this risk was increased by caries (4.323) but not
      by age. CONCLUSIONS: Since the DMFT could be one of the determining factors for
      worst quality of life in pregnant patients, more studies to corroborate this
      information are necessary in order to expand preventive expectations in the
      practice of oral health in relation to policies.

PMID- 30183953
TI  - [University and suicidal behavior: institutional response and actions, Bogota
      2004-2014].
AB  - OBJECTIVE : To analyze the institutional responses and actions towards suicidal
      behavior of students from five universities in Bogota, and their relation with
      the National Mental Health Policy (NMHP), the Comprehensive Primary Health Care
      Guidelines (APS), and the plans established for approaching this issue, to
      finally make suggestions based on them. METHODS: Qualitative, exploratory
      descriptive study based on the experiences of 66 university workers, who provided
      inputs on suicide and its characteristics; this study is also grounded on the
      institutional response of five universities in Bogota. Semi-structured interviews
      were also used. RESULTS: Participating universities have a heteronomous
      understanding of the phenomenon of suicide, as well as different attention
      mechanisms, which are mainly directed to administrative support and the
      prevention of suicidal behavior contagion. CONCLUSIONS: The consummate suicides
      of students have served the universities to reflect upon this problem, which has
      made more visible the problem of dehumanization in training, and the role of
      university well-being and health services. The appropriateness of inter
      institutional and intersectoral networks, psychoeducation, co-responsibility, and
      the active participation of young people in the discussion and formulation of
      welfare-oriented approaches and programs are strong aspects that arise from this
      reflection.

PMID- 30183954
TI  - [Longitudinal evaluation of functional neurodevelopmental diagnosis according to
      the Munich Method in preterm infants].
AB  - OBJECTIVE: The natural acquisition of motor skills during childhood can be
      affected by a gestational age of less than 40 weeks. Early detection favors
      timely management and prevention of sequelae, therefore, having a reliable tool
      for evaluating motor development in preterm children is necessary. A useful tool
      for this purpose is the Munich functional developmental diagnosis, which
      evaluates development ontogeny during the first year of life in children. This
      paper aims at analyzing the correlation between the Munich functional
      developmental diagnosis and the clinical assessment to determine the usefulness
      of such method in preterm patients. METHODS : Descriptive and retrospective
      study, in which the clinical records of 165 children with corrected age between 0
      and 12 months of age and a history of gestational age of less than 40 weeks were
      evaluated. The method was used with all the children during a follow-up visit at
      Instituto Materno Infantil in Bogota, between 2008 and 2011. RESULTS: A high
      correlation between corrected age and motor age obtained was found according to
      the Munich functional developmental diagnosis method. CONCLUSIONS: The high
      correlation between each milestone evaluated and the corrected age of preterm
      infants makes the Munich method useful for the evaluation of motor development
      since this is a short test, easy to apply.

PMID- 30183955
TI  - [Reliability of anthropometric and physiological indicators for the development
      of an elderly health index].
AB  - OBJECTIVE : To assess the reliability of anthropometric and physiological
      indicators for the development of a health index for the senior population.
      METHODS: A cross-sectional quantitative study was conducted with a sample of 63
      senior men and women participating in the Movimenta Cruz das Almas Project, of
      the Family Health Program (PSF in Portuguese) in Cruz das Almas, Bahia (Brazil).
      The age of the sample was equal to or greater than 60 years, and included 58
      females and five males. A multivariate statistical cluster analysis was performed
      and the Spearman's rho was used to determine the intensity of the association.
      Finally, the Kruskal-Wallis test was used to measure scores at the ordinal level
      (p<0.05). RESULTS: The individuals included in the sample had a mean age of
      64.29+/-4.55 years. Most of them were in the pre-elderly group (61.90 %),
      followed by young elders (26.37 %), middle aged elders (10.47 %) and advanced age
      seniors (1.26 %). The statistical cluster analysis seemed to be feasible for
      identifying and validating health indexes for the elderly. When determining the
      degree of correlation between the variables, the Spearman's test (p=0.0188)
      showed a statistically significant correlation, while the Kruskal-Wallis test
      (p=0.0018) found a highly significant correlation (H=15.0230). CONCLUSION:
      Results point to the efficiency and reliability of anthropometric and
      physiological variables for the classification of indicators in the development
      of health indexes.

PMID- 30183956
TI  - [Program for the prevention of chronic kidney disease based on integrated service
      networks in Colombia].
AB  - OBJECTIVE: Chronic Kidney Disease (CKD) prevention programs allow to control
      morbidity and/or delay renal replacement therapy. The design of a CKD prevention
      program is described, including highlights on how the primary and secondary
      levels of care interact with each other through the characterization of the
      population admitted for secondary prevention. METHODS: The description of the
      program was based on a literature review. Descriptive statistics were used to
      characterize the patients participating in the program. RESULTS: The design and
      implementation of the prevention program was based on the integration of service
      networks and care levels. The main activities for the program were detailed
      according to the care level in which they performed. 3 487 patients in total were
      admitted for control at the second care level due to an estimated glomerular
      filtration rate of <60 mil/min; 87.81% of the patients were admitted with CKD
      stage 3 and a median glomerular filtration rate of 46.21mil/min. The main causes
      of CKD were hypertension and diabetes. On admission, 2 129 patients (61.05 %) had
      systolic blood pressure <140 mmHg and 3 091 (88.64 %) had diastolic blood
      pressure <90 mmHg; 357 (57.58 %), out of 620, diabetic patients with glycosylated
      hemoglobin presented values <7.5 %. CONCLUSION : A prevention program was
      designed and implemented to allow the integration of care levels oriented to a
      multidisciplinary intervention, which ultimately managed to recognize patients
      and to give continuity to care provision for a better control of CKD.

PMID- 30183957
TI  - [Physician and family perception of the results of multiple orthopedic surgeries
      in children with cerebral palsy].
AB  - OBJECTIVE: To compare the perception of physicians and families regarding the
      results of multilevel orthopedic surgery of the lower limbs to improve gait in
      children with cerebral palsy. METHODS: An evaluation of medical records and pre-
      and postoperative videos of children attended in the walking laboratory was
      carried out. The outcome of the surgical treatment was evaluated by applying not
      only the physician rating scale, but also the Gillette functional assessment
      questionnaire (FAQ), as well as perception questionnaires to assess the
      relatives' perspective. RESULTS: 243 patients were evaluated. According to the
      functional evaluation questionnaire, 45 cases worsened, 103 improved and 95
      remained stable (p<0.001). The physician rating scale showed that gait got worse
      in 13 cases, improved in 210 and was the same in 20. The overall perception of
      the treatment outcome was favorable among relatives. A weak but significant
      correlation between the change in the physician's average score and family
      satisfaction (r=0.15; p=0.016) was found, as well as between the physician's
      overall perception and the family's perception (r=1, 5; p=0.015). CONCLUSIONS:
      The results of the surgical treatment were favorable for both the physician and
      the family. Although most cases retained functional status according to the gross
      motor function classification system (GMFCS), a significant proportion of
      patients improved according to the Gillette functional assessment questionnaire
      (FAQ).

PMID- 30183958
TI  - Video-based assessment of pedestrian behavior: Development and testing of
      methods.
AB  - OBJECTIVE: The aim of this paper is to develop a computer algorithm that analyzes
      pedestrian behavior at an urban site in Bogota, Colombia, considering that the
      assessment of pedestrian behavior is a road safety priority. METHODS: Pedestrians
      were video-taped as they crossed a selected road. An algorithm was developed in
      order to record, from these videos, pedestrian and vehicle positions and speeds.
      This information made possible the identification of hazardous behaviors, which
      were compared through visual assessments. RESULTS: 429 pedestrians crossed the
      selected road at an average distance of 4.5 meters from vehicles that moved at an
      average speed of 21 km/h. With a maximum difference of 19 % with respect to
      visual assessments, the algorithm estimated that 58.5 % pedestrians crossed
      through non-designated locations; 62.2 % crossed near moving vehicles, and that
      41.2 % ran while they were crossing the road. CONCLUSIONS: Video-based analysis
      can be used to assess pedestrians' behavior. Future research work should focus on
      improving both the accuracy and the number of safety parameters of the algorithm.

PMID- 30183959
TI  - [Cardiovascular risk factors in urban and rural communities from Tinaquillo,
      Venezuela].
AB  - OBJECTIVE: To compare the frequency of major clinical, biochemical and
      anthropometric cardiovascular risk factors between a rural community and an urban
      community from Tinaquillo, Venezuela. METHOD: 118 individuals older than 18 years
      (52 of the urban community and 66 of the rural community) were included; their
      weight, height, waist circumference, blood pressure, blood glucose and lipid
      profile were assessed. A survey to measure personal history of cardiovascular
      disease and lifestyle was applied. RESULTS: About 60 % of the individuals of the
      rural community were either obese or overweight; similar figures were obtained in
      the urban community with no statistically significant differences. Almost half of
      the participants had abdominal obesity, and also a significant frequency of
      individuals with low HDLc (greater than 70 %) was observed. It should be noted
      that although low percentages of hypertriglyceridemia were obtained, they were
      significantly higher in the rural community (chi-square=4.82, p=0.0281). The
      opposite occurs with the frequency of smoking, which is statistically higher in
      the urban community (chi-square=4.48, p=0.0342). CONCLUSIONS: The results show a
      high prevalence of cardiovascular risk factors in both communities. Consequently,
      health promotion programs should reach out to rural communities, as the risk of
      cardiovascular disease is similar to that of the urban community, who are equally
      prone to acquire unhealthy habits.

PMID- 30183960
TI  - [Adjusted force of Dengue infection].
AB  - OBJECTIVE: To propose a vector-host mathematical model for adjusting the force of
      infection with dengue in a variable population with logistic growth and a
      mosquito life cycle with periodic oviposition rate, considering immunity to a
      serotype. METHODS : The proposed mathematical model is represented by eight
      differential equations that calculate the force of infection through the scale
      free network method. RESULTS: A simulation of the mathematical model solved by an
      algorithm implemented in MATLAB based on data obtained from the literature was
      obtained. The growth of the force of dengue infection over time can be observed
      in the simulation, and it varies as some parameters change. CONCLUSIONS: The
      force of infection increases over time, that is, the rate of new cases increases,
      which proves the need for prevention among inhabitants of high-risk areas through
      the use of metallic fabrics, mosquito nets, repellents, appropriate clothing,
      among other measures. Chemical control against the vector, such as larvicides and
      adulticides, as well as the elimination of breeding places to interrupt their
      life cycle are strongly advised.

PMID- 30183961
TI  - [Contribution of universality to achieve equity in health].
AB  - This article presents a characterization of the different approaches to the
      analysis of equity in terms of equality, justice, distribution of resources,
      provision of services and risk management, based on the definition provided by
      different authors in the past two decades on this topic. It is also evident that
      the implementation of universalization policies in health programs has been a
      strategy for achieving equity, grounded on liberal approaches such as increased
      coverage, and egalitarian perspectives such as the universalization of access.
      Health reforms based on these equity approaches have not been enough to achieve
      equality yet because they maintain segregation and allow different types of
      services to different population groups, which is far from being a truly
      universal and equitable system. The purpose of this review is to elucidate the
      relationship between the principles of universalization and equity to understand
      the application of both principles in the health system of Colombia.

PMID- 30183962
TI  - [Prevalence of leptospirosis in Colombia: systematic literature review].
AB  - OBJECTIVE : To conduct a systematic literature review to identify the prevalence
      of leptospirosis in Colombia between 2000 and 2012. METHODS : Descriptive studies
      conducted and published between 2000 and 2012 on the prevalence of leptospirosis
      in humans, animals and the environment using microagglutination (MAT) and
      immunoassay (ELISA) diagnostic methods, were selected. The exclusion criteria
      included studies in languages other than Spanish, English and Portuguese, in
      which the prevalence of leptospirosis was determined by immunofluorescence (IF),
      or serum agglutination test (SAT). RESULTS : Out of 91 articles reviewed in the
      different databases, 18 were selected since they met the inclusion criteria,
      which sought to determine the prevalence of leptospirosis in humans, canines,
      cattle, pigs, primates and rodents in the Atlantico, Antioquia, Meta, Cordoba,
      Risaralda, Tolima, Boyaca, Quindio and Valle del Cauca departments. CONCLUSIONS :
      The systematic review allowed to determine the departments of the country where
      leptospirosis research is concentrated, as well as the authors with the highest
      number of publications on prevalence. The prevalence was found to be between 6%
      and 35% in humans, 41% and 60.9% in cattle, 10.3% in pigs, 12% and 47.14% in
      canines, 23.07 % in non-human primates, and the highest figure, between 25% and
      82.7% in rodents, showing that the most frequent serovars were
      Icterohaemorrhagiae, Grippotyphosa and Canicola.

PMID- 30183963
TI  - [Long stay institutions as an alternative for protecting the elderly].
AB  - This is a reflective study on long stay institutions for elderly population.
      Considering the context in which the process of institutionalization in a long
      stay institution for the elderly occurs, which is escorted by changes in every
      day life of the elderly population, this study aims to reflect on the long-stay
      institutions as an alternative of sheltering for the Brazilian elderly. First,
      demographic aging is analyzed, followed by a brief historical account regarding
      long-stay institutions, and an approach to the institutionalization process of
      the elderly population in these places. Although the functions and duties of long
      stay institutions have been previously defined, the negative aspects that
      influence the experience of institutionalized elderly are evident; therefore,
      restructuring the environment of these type of places is necessary considering
      the growing demand. The institutionalization process and the experience of the
      elderly population admitted to these institutions are key study elements to
      comprehend the intrinsic reality of this population.

PMID- 30183964
TI  - [Sanitary control of health services: a dimension of universality].
AB  - The sanitary control of health services is one of the activities related to
      health surveillance, which establishes environmental, procedures, human resources
      and management conditions of risk control system of these services. In Brazil,
      all citizens are subjected to the rules and benefits of proper sanitary control.
      This paper presents a reflection on the current scenario of Health Surveillance
      of the Brazilian Health Services, as well as its limitations and potentialities
      for more effective development of these actions in the light of universality.

PMID- 30183965
TI  - [Payment to providers of health services in Bogota].
AB  - OBJECTIVE: To review the concepts, developments and effects of the payment
      mechanisms used in different countries to propose a payment methodology
      applicable to hospitals in Bogota. METHOD: Literature review in which essential
      concepts, developments and effects derived from payment mechanisms used in
      different countries were analyzed. The authors and various groups and teams of
      the Bogota Health Department participated, hospitals, academia and national
      health authorities held work sessions with the intention of creating a
      methodological design for a payment scheme that could be applied to the hospitals
      attached to the health network in Bogota. RESULTS: The literature review allowed
      establishing work axes for a prospective payment scheme per network that included
      performance bonuses based on the optimization of technical efficiency (provision
      of health services at lower cost, locative efficiency (optimization of the mix of
      health services), and on better care outcomes. DISCUSSION: The proposed payment
      scheme should be an integrating factor in the patient care process, and should
      also result in a better operation, service delivery and health care governance,
      while optimizing the flow of resources and local sustainability.

PMID- 30183966
TI  - [Prioritization for public health information analysis in Colombia. Knowledge
      network at the National Health Observatory].
AB  - OBJECTIVE: To prioritize diseases, population and methods of analysis in public
      health according to the preferences of the stakeholders of the knowledge network
      of the National Health Observatory. METHOD: The conjoint analysis methodology
      (AC) was used; it consists on the construction of a complete factorial model
      taking a random sample of subjects that must identify the preferences of the
      attributes of a given construct according to a pre-established order of
      importance. The stakeholders of the knowledge network who participated were
      professionals from public universities, members of health promotion entities,
      health provision services, health departments, non-profit health organizations,
      specialized research centers, mayor's offices, and corporations. RESULTS: The
      groups of priority diseases were mental and behavioral disorders (13.8%),
      cardiovascular and circulatory diseases (13%), neoplasms (10%), diarrhea,
      respiratory infections, meningitis and other common infectious diseases (6.7%),
      and nutritional deficiencies (6.3 %). The preferred prioritization criteria were
      the burden of disease and high-impact epidemiological dynamics. The analysis of
      priority information was the analysis of social determinants. The most preferred
      population was the general population. CONCLUSIONS: Participants perceive both
      chronic and infectious diseases as a priority, which is consistent with the
      epidemiological transition of the country. The priority for the Colombian health
      system is to strengthen the capacity of human resources and the surveillance
      system in different areas to have a better decision-making process in relation to
      public health.

PMID- 30183967
TI  - [Estimation of the global burden of disease in Colombia-2012: new methodological
      aspects].
AB  - The new methodology applying for burden of disease study (GBD 2010) is difficult
      to completely reproduce in Colombia. This paper presents the results of partial
      use of this methodology to estimate the components years lost due to premature
      death (YLLs) and lived with disability (YLDs). Redistribution of useless codes
      produces significant increases in some causes of death, which are preferable to
      deal with an analysis of causes of death with 15,6 % of useless codes that would
      provide little or no statistical information. Ischemic heart disease,
      cerebrovascular and hypertensive heart disease events cause the highest risk of
      mortality rate (164,2 per 100,000). Assaults by firearms and sharp objects, self
      inflicted injuries and those caused by motorcycles and four-wheeled vehicles on
      the road, are the first cause of YLLs per 1000 (34,3). Skin diseases such as
      dermatitis, erythemas, burns on exposure to sunlight, pediculosis and pityriasis,
      cause the greatest risk of YLDs per 1000 (51,3). This group of skin diseases are
      also the leading cause of DALYs per 1000 (51,4). The departments with the highest
      rates of mortality and YLLs for Group I (communicable diseases) are Guainia,
      Amazonas, Vaupes, Cauca, Vichada, Putumayo, Narino, Choco, Cordoba, La Guajira,
      Guaviare y Caqueta and with the lower mortality coverage.

PMID- 30183968
TI  - [A model for mortality analysis in Colombia. 2000-2012].
AB  - OBJECTIVE : To propose and evaluate a model for fitting and forecasting the
      mortality rates in Colombia that allows analyzing the trends by age, sex, region
      and cause of death. METHODOLOGY : The national death registries were used as
      primary source of analysis. The data was pre-processed recodifying the cause of
      death and redistributing the garbage codes. The forecast model was formulated as
      a linear approximation with a set of variables of interest, in particular the
      population and gross domestic product (GDP) by region. RESULTS : As study case we
      took the mortality under 5 years old, it decreased steadily since 2000 at the
      national level and at most of the regions. The predictive power of the proposed
      methodology was tested by fitting the model with the data from 2000 to 2011, the
      forecast for 2012 was compared with the actual rate, and these results show the
      model is reliable enough for most of the region-cause combinations. CONCLUSIONS :
      The proposed methodology and model have the potential to become an instrument to
      guide health spending priorities using some kind of evidence.

PMID- 30183969
TI  - [Composite Index of health Inequity for a Middle Income Country].
AB  - OBJECTIVE : To develop and validate a composite index of health inequity based on
      mortality by grouped causes. METHODS : An ecological study in a middle-income
      Latin American country, with aggregate indicators available from municipalities
      and departments, which were selected from health observatories, research groups
      and health authorities. They were divided into intolerable and "not completely
      avoidable" according to current scientific progress, and were added in
      categories: traffic accident, aggression, kidney disease, HIV infection,
      intestinal parasitic diseases, syphilis, fecal / oral transmission disease,
      tuberculosis, disease Vector-borne diseases, respiratory disease, cerebral
      hemorrhagic / ischemic events, maternal mortality, lower mortality 5 years,
      meningitis. After analysis of main components, a composite index of health
      inequity (IIS) is obtained for men and women. Internal consistency was evaluated
      using Cronbach's Alpha coefficient. Concurrent validation was done with
      proportion of people in Unsatisfied Basic Needs (UBN), Human Development Index
      (HDI), Life Expectancy at Birth (LEB), among others. RESULTS : IIS is built
      showing higher values for women in most municipalities and departments; And for
      sites with high HDI, high LEB and low UBN. Cronbach's alpha was 0.6688, IIS-men
      and 0.725, IIS-women. CONCLUSIONS : An IIS was obtained, is valid and
      reproducible. The role of big cities in inequities in health is highlighted,
      probably due to the effect of intolerable health.

PMID- 30183970
TI  - [Surveillance and analysis of border areas, ports of entry and immigrant
      population].
AB  - OBJECTIVE : Perform a literature review about systems of sanitary and
      epidemiological surveillance for frontier zones and the points of entry of
      Colombia. MATERIALS AND METHODS : A systematic literature review using the Prisma
      methodology, MeSH and DECS terms, was developed in PubMed and BVS bibliographic
      databases between 2000 and 2014. We included 51 documents according to inclusion
      exclusion criteria and we proposed and discussed these categories: health
      services, mental health, health status and social determinants. RESULTS : The
      analysis makes it possible to evidence that the epidemiological and sanitary
      surveillance of borders and entry points worldwide, focused mainly on axes such
      as mental health, transmissible events and events of non-communicable conditions.
      In addition, the importance of comprehensive care in health services, as well as
      the analysis of the health status of immigrant population under the territorial,
      ethnic and cultural differential approach. However, there are few experiences
      with a social determinants analysis in borders zone and / or entry points.
      CONCLUSIONS : Differences in the context, health systems, information systems and
      priorities of each country make the exchange and cooperation between borders
      challenging. It is necessary to have instruments of cooperation between
      neighboring countries and a common information based on the Social Determinants
      of Health.

PMID- 30183971
TI  - [Methodological guidelines to evaluate public health policies, and assessment of
      food and nutritional security policies].
AB  - OBJECTIVE: To evaluate the Food and Nutrition Security Policy of Colombia (PSAN
      by its acronym in Spanish). METHODOLOGY: A qualitative formative evaluation was
      applied, based on an academic focus, to validate the methodology established by
      the "Methodological guidelines for the assessment and analysis of public health
      policies." This evaluation inquired about the following aspects: Does the design
      of the Food and Nutrition Security Policy comply with the coherence between the
      problem, the proposed solutions and the proposed measures? What is the progress
      in objective compliance during the implementation? RESULTS: The Nutritional Food
      Security Policy (PSNP in Spanish) is pertinent and consistent with the diagnosis.
      Its objectives and strategies correlate, and aim to solve the problem of food and
      nutrition insecurity of the entire population of the country, especially, the
      poorest and more vulnerable. This policy is relevant because the activities
      programmed in the action plan of the National Plan for Food and Nutrition
      Security 2012-2019 are aligned with the needs and priorities of the territory,
      and with the institutional offer of the entities that participate in the
      development of the policy. CONCLUSIONS: Redesigning PSAN according to the current
      dynamics of the country in terms of international commitments, the objectives of
      sustainable development, the right to food, sovereignty and governance in food
      and nutrition security, and the approach of social determinants in health.

PMID- 30183972
TI  - [Need for promotion, prevention and intervention in mental health in Peru].

PMID- 30183973
TI  - ERRATUM.
AB  - [This corrects the article doi: 10.1590/s1806-37562017000000185].

PMID- 30183974
TI  - Captopril alleviates hypertension-induced renal damage, inflammation, and NF
      kappaB activation.
AB  - Hypertensive renal damage generally occurs during the middle and late stages of
      hypertension, which is typically characterized by proteinuria and renal
      inflammation. Captopril, an angiotensin-converting enzyme (ACE) inhibitor, has
      been widely used for therapy of arterial hypertension and cardiovascular
      diseases. However, the protective effects of captopril on hypertension-induced
      organ damage remain elusive. The present study was designed to explore the
      renoprotective action of captopril in spontaneously hypertensive rats (SHR). The
      6-week-old male SHR and age-matched Wistar-Kyoto rats were randomized into long
      term captopril-treated (34 mg/kg) and vehicle-treated groups. The results showed
      that in SHR there was obvious renal injury characterized by the increased levels
      of urine albumin, total protein, serum creatinine, blood urea nitrogen, renal
      inflammation manifested by the increased mRNA and protein expression of
      inflammatory factors including tumor necrosis factor-alpha, interleukin (IL)
      1beta, IL-6, and inducible nitric oxide synthase, and enhanced nuclear factor
      kappaB (NF-kappaB) activation. Captopril treatment could lower blood pressure,
      improve renal injury, and suppress renal inflammation and NF-kappaB activation in
      SHR rats. In conclusion, captopril ameliorates renal injury and inflammation in
      SHR possibly via inactivation of NF-kappaB signaling.

PMID- 30183975
TI  - Effect of a palliative care program on trends in intensive care unit utilization
      and do-not-resuscitate orders during terminal hospitalizations. An interrupted
      time series analysis.
AB  - OBJECTIVE: To assess the effect of the implementation of a palliative care
      program on do-not-resuscitate orders and intensive care unit utilization during
      terminal hospitalizations. METHODS: Data were retrospectively collected for all
      patients who died in a tertiary hospital in Brazil from May 2014 to September
      2016. We analyzed the frequency of do-not-resuscitate orders and intensive care
      unit admissions among in-hospital deaths. Interrupted time series analyses were
      used to evaluate differences in trends of do-not-resuscitate orders and intensive
      care unit admissions before (17 months) and after (12 months) the implementation
      of a palliative care program. RESULTS: We analyzed 48,372 hospital admissions and
      1,071 in-hospital deaths. Deaths were preceded by do-not-resuscitate orders in
      276 (25.8%) cases and admissions to the intensive care unit occurred in 814 (76%)
      cases. Do-not-resuscitate orders increased from 125 (20.4%) to 151 (33%) cases in
      the pre-implementation and post-implementation periods, respectively (p < 0.001).
      Intensive care unit admissions occurred in 469 (76.5%) and 345 (75.3%) cases in
      the pre-implementation and post-implementation periods, respectively (p = 0.654).
      Interrupted time series analyses confirmed a trend of increased do-not
      resuscitate order registrations, from an increase of 0.5% per month pre
      implementation to an increase of 2.9% per month post-implementation (p < 0.001),
      and demonstrated a trend of decreased intensive care unit utilization, from an
      increase of 0.6% per month pre-implementation to a decrease of -0.9% per month in
      the post-implementation period (p = 0.001). CONCLUSION: The implementation of a
      palliative care program was associated with a trend of increased registration of
      do-not-resuscitate orders and a trend of decreased intensive care unit
      utilization during terminal hospitalizations.

PMID- 30183977
TI  - The practice of dentistry in intensive care units in Brazil.
AB  - OBJECTIVE: To evaluate the practice of dentistry in intensive care units.
      METHODS: An observational survey study was conducted in which questionnaires were
      sent via the online platform for collaboration in intensive care research in
      Brazil (AMIBnet). The study was carried out from June to October 2017. The
      questionnaires, which contained 26 closed questions about hospitals and dentistry
      practices in the intensive care units, were sent to 4,569 professionals from
      different specialties practicing in the units. RESULTS: In total, 203
      questionnaires were returned, resulting in a response rate of 4.44%. Most of the
      responses were from intensive care units in the Southeast region of the country
      (46.8%). Public hospitals (37.9%) and private hospitals (36.4%) had similar
      participation rates. Of the respondents, 55% indicated that a bedside dentistry
      service was present, and they were provided in different ways. CONCLUSION: The
      presence of dentistry services and oral health service delivery training and
      protocols were correlated. The oral care methods varied greatly among the
      intensive care units surveyed.

PMID- 30183976
TI  - Brazilian version of the Pediatric Functional Status Scale: translation and cross
      cultural adaptation.
AB  - OBJECTIVE: To translate and cross-culturally adapt the Functional Status Scale
      for hospitalized children into Brazilian Portuguese. METHODS: A methodological
      study of the translation and cross-cultural adaptation of the Functional Status
      Scale was conducted, according to the stages of translation, synthesis of
      translations, back-translation, synthesis of back-translations, expert committee
      analysis and pre-test with a sample of the target population. During the
      evaluation by the committee of experts, semantic, content and item analyses were
      performed. RESULTS: The semantic, idiomatic, cultural and conceptual equivalences
      between the translated version and the original version were obtained, resulting
      in the Brazilian version of the Functional Status Scale. After the analysis by
      the expert committee, there were no problems regarding the cultural or conceptual
      equivalences because the items were pertinent to the Brazilian culture and few
      terms were modified. In the pre-test stage, the scale was applied by two
      evaluators to a sample of 25 children. Clarity and ease in answering the scale
      items were observed. Good inter-observer reliability was obtained, with an
      intraclass correlation coefficient of 0.85 (0.59 - 0.95). CONCLUSIONS: The
      Functional Status Scale for pediatric use was translated and culturally adapted
      into Portuguese spoken in Brazil. The translated items were pertinent to the
      Brazilian culture and evaluated the dimensions proposed by the original
      instrument. Validation studies of this instrument are suggested to make it
      feasible for use in different regions of Brazil.

PMID- 30183978
TI  - Microcirculation and Cardiovascular Diseases.

PMID- 30183979
TI  - Atrial Fibrillation and Cryptogenic Thromboembolic Events.

PMID- 30183980
TI  - Persistent Inflammatory Activity in Blood Cells and Artery Tissue from Patients
      with Previous Bare Metal Stent.

PMID- 30183982
TI  - Are We Taking Good Care of Our Patients and Physicians?

PMID- 30183981
TI  - Satisfaction of Emergency Physicians with the Care Provided to Patients with
      Cardiovascular Diseases in the Northern Region of Minas Gerais.
AB  - BACKGROUND: The dissatisfaction of health professionals in emergency services has
      a negative influence on both the quality of care provided for acute myocardial
      infarction (AMI) patients and the retention of those professionals. OBJECTIVE: To
      assess physicians' satisfaction with the structure of care and diagnosis at the
      emergency services in the Northern Region of Minas Gerais before the
      implementation of the AMI system of care. METHODS: This cross-sectional study
      included physicians from the emergency units of the ambulance service (SAMU) and
      level II, III and IV regional hospitals. Satisfaction was assessed by using the
      CARDIOSATIS-Team scale. The median score for each item, the overall scale and the
      domains were calculated and then compared by groups using the non-parametric Mann
      Whitney test. Correlation between time since graduation and satisfaction level
      was assessed using Spearman correlation. A p value < 0.05 was considered
      significant. RESULTS: Of the 137 physicians included in the study, 46% worked at
      SAMU. Most of the interviewees showed overall dissatisfaction with the structure
      of care, and the median score for the overall scale was 2.0 [interquartile range
      (IQR) 2.0-4.0]. Most SAMU physicians expressed their dissatisfaction with the
      care provided (54%), the structure for managing cardiovascular diseases (52%),
      and the technology available for diagnosis (54%). The evaluation of the overall
      satisfaction evidenced that the dissatisfaction of SAMU physicians was lower when
      compared to that of hospital emergency physicians. Level III/IV hospital
      physicians expressed greater overall satisfaction when compared to level II
      hospital physicians. CONCLUSION: This study showed the overall dissatisfaction of
      the emergency physicians in the region assessed with the structure of care for
      cardiovascular emergencies.

PMID- 30183983
TI  - VEGFR-2: One of Pioglitazone's Signaling Pathways in the Heart.

PMID- 30183984
TI  - Hypertension and Exercise: A Search for Mechanisms.

PMID- 30183985
TI  - Cardiac Sympathetic Activity and the Neuro-Humoral Theory on Heart Failure with
      Reduced Ejection Fraction: Have We Learned Enough?

PMID- 30183987
TI  - New Method Improves the Assessment of Aortic Regurgitation Grade during TAVR by
      Aortography.

PMID- 30183986
TI  - The Role of Quantitative Aortographic Assessment of Aortic Regurgitation by
      Videodensitometry in the Guidance of Transcatheter Aortic Valve Implantation.
AB  - BACKGROUND: Balloon post-dilatation (BPD) is often needed for optimizing
      transcatheter heart valve (THV) implantation, since paravalvular leak (PVL) after
      transcatheter aortic valve implantation is associated with poor outcome and
      mortality. Quantitative assessment of PVL severity before and after BPD is
      mandatory to properly assess PVL, thus improving implantation results and
      outcomes. OBJECTIVE: To investigate a quantitative angiographic assessment of
      aortic regurgitation (AR) by videodensitometry before and after BPD. METHODS:
      Videodensitometric-AR assessments (VD-AR) before and after BPD were analysed in
      61 cases. RESULTS: VD-AR decreased significantly from 24.0[18.0-30.5]% to
      12.0[5.5-19.0]% (p < 0.001, a two-tailed p < 0.05 defined the statistical
      significance). The relative delta of VD-AR after BPD ranged from -100%
      (improvement) to +40% (deterioration) and its median value was -46.2%. The
      frequency of improvement, no change, and deterioration were 70% (n = 43), 25% (n
      = 15) and 5% (n = 3), respectively. Significant AR (VD-AR > 17%) was observed in
      47 patients (77%) before and in 19 patients (31%) after BPD. CONCLUSIONS: VD-AR
      after THV implantation provides a quantitative assessment of post-TAVI
      regurgitation and can help in the decision-making process on performing BPD and
      in determining its efficacy.

PMID- 30183989
TI  - Downstream Change of the Primary Endpoint in the ISCHEMIA Trial: the Elephant in
      the Room.

PMID- 30183988
TI  - Antiplatelet Therapy in Breast Cancer Patients Using Hormonal Therapy: Myths,
      Evidence and Potentialities - Systematic Review.
AB  - Breast cancer is the most frequently diagnosed tumor in women worldwide, with a
      significant impact on morbidity and mortality. Chemotherapy and hormone therapy
      have significantly reduced mortality; however, the adverse effects are
      significant. Aspirin has been incorporated into clinical practice for over 100
      years at a low cost, making it particularly attractive as a potential agent in
      breast cancer prevention and as an adjunct treatment to endocrine therapy in the
      prophylaxis of cardiovascular complications. The objective of this study was to
      evaluate the role of aspirin in reducing the incidence of breast cancer and to
      evaluate the impact of its use on morbidity and mortality and reduction of
      cardiovascular events as adjuvant therapy during breast cancer treatment with
      selective estrogen receptor modulators. A systematic review was performed using
      the PRISMA methodology and PICO criteria, based on the MEDLINE, EMBASE and LILACS
      databases. The original articles of clinical trials, cohort, case-control studies
      and meta-analyses published from January 1998 to June 2017, were considered. Most
      studies showed an association between the use of selective estrogen receptor
      modulators and the increase in thromboembolic events. The studies suggest a
      protective effect of aspirin for cardiovascular events during its concomitant use
      with selective estrogen receptor modulators and in the prevention of breast
      cancer. This systematic review suggests that aspirin therapy combines the benefit
      of protection against cardiovascular events with the potential reduction in
      breast cancer risk, and that the evaluation of the benefits of the interaction of
      endocrine therapy with aspirin should be further investigated.

PMID- 30183990
TI  - Case 4 - A 59-Year-Old Woman with Rheumatic Mitral Valve Disease (Severe Stenosis
      and Regurgitation), Severe Dyspnea, Shock and Pulmonary Condensation.

PMID- 30183991
TI  - Transcatheter Closure of a Traumatic VSD with an ASD Occluder.

PMID- 30183992
TI  - Unexpected Mass in the Left Atrium.

PMID- 30183993
TI  - The Need for Sex Hormone Analysis in Addition to Long-Term Follow-Up of
      Phytosterol SupplementationPhytosterols in the Treatment of Hypercholesterolemia
      and Prevention of Cardiovascular DiseasesThe effects of phytosterols on the
      sexual behavior and reproductive function in the Japanese quail (Coturnix
      coturnix japonica)Phytosterol feeding induces alteration in testosterone
      metabolism in rat tissuesMultigenerational exposure to phytosterols in the mouse.

PMID- 30183994
TI  - Light microscopy and surface topography of Urotrema scabridum and Renschetrema
      indicum (Digenea) from Rhinopoma hardwickii (Chiroptera): first report in Egypt.
AB  - This report introduced the description of two different species of digenean
      parasites isolated from the intestine of Rhinopoma hardwickii with new host and
      locality records in Egypt. The recovered helminthes were studied morphologically
      and morphometrically by light microscopy and the surface topography of the two
      species was elucidated by scanning electron microscopy (SEM). Urotrema scabridum
      had an elongated body, testes were tandem, ovaries were pretesticular, and
      vitelline follicles were observed in 2 lateral fields. SEM showed that the
      anterior half was covered with random and backwardly directed tegument spines.
      The lumen of the oral sucker was as a longitudinal slit encircled with type I
      dome-shaped papillae. The ventral sucker was wrinkled and covered by tongue
      shaped tegument spines and several scattered papillae. Renschetrema indicum had a
      fusiform body with minute spines densely distributed in the anterior part of the
      body; testes sub-triangular, ovary fusiform; vitellaria were randomly distributed
      around the ceca and genital organs. SEM showed that the fore-body was ventrally
      concave and surrounded by cytoplasmic ridges equipped with numerous closely
      packed claw-shaped spines. The oral sucker was externally surrounded by two
      circles of papillae while the lip of the ventral sucker was rounded and
      surrounded by three papillae located in its upper end and anterolaterally.

PMID- 30183995
TI  - Occurrence of anti-Neospora caninum antibodies in cattle in the dairy farming
      region of the state of Piaui, Brazil.
AB  - This study focused on the detection of anti-Neospora caninum IgG antibodies in
      cows in the dairy farming region of the state of Piaui, Brazil. To this end,
      serum samples were collected from 255 dairy cows on 17 farms located in the dairy
      farming region of the municipality of Parnaiba, Piaui, Brazil. The indirect
      fluorescence antibody test (IFAT) was employed to detect anti-N. caninum IgG
      antibodies, using anti-bovine IgG (Sigma(r)) conjugated to fluorescein
      isothiocyanate (FITC) and a cutoff point of 1:200. Of the 255 samples analyzed,
      69 (27.06%) were positive for anti- N. caninum IgG antibodies, the relative
      frequency found by property was: 1 (20.00%), 2 (53.33%), 3 (46.66%), 4 (53.33%),
      5 (26.66%), 6 (6.66%), 7 (6.66%), 8 (20.00%), 9 (26.66%), 10 (26.66%), 11
      (20.00%), 12 (20.00%), 13 (46.66%), 14 (26.66%), 15 (26.66%), 16 (20.00%) and 17
      (13.33%). with titers of 200 (15.94%), 400 (20.30%), 800 (24.63%), 1600 (23.18%)
      and 3200 (15.94%), being the highest frequency for the titer of 800. This study
      demonstrates for the first time that cows from dairy herds of Parnaiba
      municipality, state of Piaui, are exposed to N. caninum.

PMID- 30183996
TI  - Association of Epistylis spp. (Ciliophora: Peritrichia) with parasitic
      crustaceans in farmed piava Megaleporinus obtusidens (Characiformes:
      Anostomidae).
AB  - Parasitic diseases have caused significant problems to global aquaculture
      production. These studies will further our knowledge of this complex problem and
      help implement adequate prevention measures and control strategies. The present
      study aimed to investigate the presence of parasites in Megaleporinus obtusidens
      and to describe the epidemiology and pathology of parasitic infections in these
      fish. Five moribund fish were sent for parasitological examination. The
      integument and gills were scrapped off with a glass slide, and samples were
      examined under a light microscope. Parasitic crustaceans found in these specimens
      were submitted for scanning electron microscopy and histological analyses. The
      crustaceans Dolops carvalhoi and Lernaea cyprinacea and the Epistylis spp. were
      present in all fish examined. Epistylis spp. were also seen on the entire surface
      of the crustacean integument. Microscopic lesions observed in the parasitized
      gills included hyperplasia and hypertrophy of the lamellar epithelium, an
      inflammatory infiltrate, telangiectasia, foci of hemorrhage and necrosis, fusion
      of the secondary lamellae, and detachment of the lamellar epithelium. Crustacean
      parasites are important mechanical vectors of Epistylis infection and disseminate
      the disease in fish farming operations. Epistylis spp. infection affects the
      health of fish and has significant ecological and economical impact on
      aquaculture.

PMID- 30183997
TI  - Molecular survey and genetic diversity of piroplasmids in equids from Midwestern
      Brazil.
AB  - We evaluated the distribution of piroplasmids in equids from the Mato Grosso
      state in Midwestern Brazil using molecular methods and the interspecific genetic
      diversity. For this, 1,624 blood samples of equids from 973 farms were examined
      by PCR, using primer pairs that amplify a fragment of the genes rap-1 and ema-1
      of Babesia caballi and Theileria equi, respectively. For molecular
      characterization and phylogenetic studies, 13 and 60 sequences of the rap-1 and
      ema-1 genes, respectively, were used to build a dendogram using maximum
      parsimony. B. caballi and T. equi were detected in 4.11% and 28.16% of the farms,
      respectively, and molecular prevalence was 2.74% for B. caballi and 25.91% for T.
      equi. The location of the farms and animals raised in the Pantanal ecoregion
      influence the probability of equids testing positive for B. caballi and T. equi .
      Moreover, age and herd purpose were variables significantly associated with T .
      equi infection. The sequences of B. caballi presented 1.95% intraspecific
      variability, contrasting with 2.99% in T. equi. Dendrograms for both species
      demonstrated the presence of subgroups with high values of support of branches.
      However, it is not possible to associate these groups with geographic origin
      and/or ecoregion.

PMID- 30183998
TI  - The effect of water source and soil supplementation on parasite contamination in
      organic vegetable gardens.
AB  - The objective of this study was to determine factors associated with vegetable
      contamination with zoonotic protozoan. Samples of water, soil and vegetables were
      collected from July/2014 to May/2016, totaling 83 samples, 21 properties of
      Londrina region, Parana, Brazil. DNA amplification of Toxoplasma gondii,
      Cryptosporidium spp. and Giardia intestinalis in the samples was conducted using
      polymerase chain reaction (PCR). The PCR results were positive for T. gondii in
      12.9% (8/62), Cryptosporidium spp. in 11.3% (7/62) and G. intestinalis in 25.8%
      (16/62) of the samples. DNA sequencing identified C. parvum in five samples and
      G. intestinalis Assemblage E in three. The statistical associations demonstrated
      greater probability of positive samples for T. gondii and for at least one of the
      three protozoa when the source of irrigation water was the river; a greater
      chance of positive samples for Cryptosporidium spp. when deer were present on the
      property; and a smaller chance of positive samples for at least one of the three
      etiologic agents when soil was supplemented with limestone. The results expose
      some critical contamination points, providing support for training farmers on
      good management practices during the production process.

PMID- 30183999
TI  - Serological, molecular, and microscopic detection of Leishmania in cats (Felis
      catus) in Belo Horizonte, Minas Gerais State, Brazil.
AB  - The role of cats in the epidemiological cycle of leishmaniasis remains unclear.
      To better understand the occurrence of leishmaniasis in cats, we studied the
      frequency of Leishmania in serum samples of 100 cats living in an endemic region
      for canine and human leishmaniasis by serological, parasitological, and molecular
      methods. Of the 100 cats, 54 were seropositive for Leishmania antibodies by
      immunofluorescence antibody test. None of the bone marrow aspirates collected
      from these cats tested positive for the parasite in culture or upon polymerase
      chain reaction (PCR) analysis. Biopsy samples of the ears also tested negative
      for Leishmania upon PCR analysis. These findings may indicate that the region is
      endemic for canine leishmaniasis and cats are infected by Leishmania; or that
      cross-reaction with antibodies against other parasites increases the frequency of
      seropositivity; or that cats respond to Leishmania infection by producing
      antibodies when few or no parasites are present in bone marrow and tissue
      samples. Overall, our results suggest that cats can be infected by Leishmania ;
      however, we failed to demonstrate feline parasitosis. These findings highlight
      the need to study leishmaniasis in cats, since sandflies feed on cats, these
      animals may act as a reservoir for the parasite.

PMID- 30184000
TI  - The dermatitis by Caparinia tripilis and Microsporum , in african pygmy hedgehog
      (Atelerix albiventris) in Romania - first report.
AB  - Investigations were conducted on a case of generalized dermatitis in an African
      pygmy hedgehog (Atelerix albiventris), purchased as a pet. Clinical examination
      revealed restlessness, agitation, itching and scratching, large alopecic areas,
      skin congestion and thin whitish scabs. Five skin lesions were scraped and the
      samples were collected for laboratory tests. Microscopy revealed the presence of
      the mite Caparinia tripilis (Acari: Psoroptidae). A dermatophyte belonging to
      Microsporum genus was also isolated by culture on specific media. Selamectin spot
      on and enilconazole washes were used for treatment, resulting in skin healing and
      spines growing. To our knowledge, this is the first reported case of Caparinia
      tripilis dermatitis in a hedgehog in Romania.

PMID- 30184001
TI  - Variables associated with the prevalence of anti-Leishmania spp. antibodies in
      dogs on the tri-border of Foz do Iguacu, Parana, Brazil.
AB  - The aim of this study was to investigate the occurrence of anti-Leishmania spp.
      antibodies in dogs from localities in the city of Foz do Iguacu, Parana state,
      Brazil, on the border with Argentina and Paraguay. Blood samples dogs were
      collected to perform the following serologic tests: immunochromatographic DPP(r)
      rapid test, indirect immunoenzymatic assay (ELISA) and indirect
      immunofluorescence assay (IFA). In 2012, 285 dogs were analyzed on Argentina
      border, and in 2013, serum samples from 396 dogs on the border of Paraguay were
      collected. Using ELISA for screening and IFA for the confirmatory test, the
      results showed that the antibody prevalence was 1.8% (5/285) on the border of
      Argentina and 3.0% (12/396) on Paraguay border. When using the DPP(r) for
      screening and ELISA as a confirmatory analysis, we observed a seroreagent
      prevalence in dogs of 2.5% (7/285) on Argentina border and 5.1% (20/396) on
      Paraguay border. The non-public collection of domestic waste (p= 0.0004) was
      shown to be associated with leishmaniasis. This study shows the presence of
      leishmaniasis and suggest the emergence of canine visceral leishmaniasis in state
      of Parana due to the confirmed occurrence of seroreactive dogs on Argentina and
      Paraguay border, which has environmental and geographical characteristics that
      favor the spread of the parasite.

PMID- 30184002
TI  - Blankaartia sinnamaryi (Trombidiformes: Trombiculidae) parasitizing birds in
      southeastern Brazil, with notes on Rickettsia detection.
AB  - The larvae of the family Trombiculidae are ectoparasites of vertebrates,
      including birds. The bite of some species can cause deep lesions and severe skin
      reactions in the host, these can lead to dermatitis, popularly known as
      trombiculiasis. A morphological study of chiggers collected on birds from the
      state of Minas Gerais in Southeastern Brazil discovered Blankaartia sinnamaryi
      infestation on Passeriformes birds. Molecular studies of the disclosed the 18S
      rDNA sequences of the mite, and the detection of a Rickettsia sp. in this chigger
      mite species.

PMID- 30184003
TI  - Seroprevalence, spatial analysis and risk factors of infection with Neospora
      caninum in cattle in Brazil's northern Pantanal wetland.
AB  - Neosporosis is caused by an obligate intracellular protozoan, Neospora caninum .
      It is considered one of the most widespread and frequent causes of abortion in
      cattle worldwide. To evaluate the prevalence of anti-N. caninum antibodies and
      associated risk factors, serum samples were collected from 2,452 bovines at 262
      farms in the northern Pantanal, state of Mato Grosso, Brazil. Each farmer was
      asked to fill out a questionnaire for subsequent epidemiological data analysis.
      Anti-N. caninum antibodies were detected by means of the indirect
      immunofluorescent assay (IFA), using a cut-off dilution of 1:100. The overall
      anti-N. caninum antibodies prevalence was 25.44% (Confidence Interval - CI 95%;
      20.10%; 30.78%), and the anti-N. caninum antibodies prevalence per herd was
      76.72% (CI 95%; 71.60%; 81.84%). The presence of dogs, occurrence of abortion in
      cows, and sale of cattle for breeding were statistically associated with
      seropositivity in herds, while the risk of females being seropositive for N.
      caninum was higher in animals <= 6-years-old and in the presence of dogs. A
      spatial analysis indicated that the relative risk of the disease is spatially
      constant and that the farms with the highest prevalence of anti-N. caninum
      antibodies are located south of the region under study.

PMID- 30184004
TI  - Isolation and genetic characterization of Toxoplasma gondii from free-ranging and
      captive birds and mammals in Pernambuco state, Brazil.
AB  - Recent genetic population studies on Toxoplasma gondii in Brazil have shown large
      genetic variability. The objective of the present study was to isolate and
      genotypically characterize T. gondii from free-ranging and captive wild mammals
      and birds in Pernambuco state, Brazil. Fragments of heart, brain, skeletal muscle
      and diaphragm tissue from 71 birds and 34 mammals, which were either free-ranging
      or captive, were collected. Samples from 32 of these animals were subjected to
      bioassays in mice. Samples from the remaining 73 animals underwent biomolecular
      diagnosis, using PCR technique, targeting a repetitive DNA fragment of 529 bp in
      T. gondii. A non-virulent isolate (TgButstBrPE1) was obtained from a free-ranging
      striated heron (Butorides striata) and, based on primary samples, seven animals
      were found to be positive. The primary samples and the isolate obtained were
      subjected to PCR-RFLP using the markers SAG1, 5'3'SAG2, alt.SAG2, SAG3, BTUB,
      GRA6, c22-8, c29-2, L358, PK1, Apico and CS3. ToxoDB-RFLP genotype #13 from the
      striated heron isolate and Type BrIII genotype from a captive otter ( Lontra
      longicaudis) (PS-TgLonloBrPE1) were obtained. The present study describes the
      first isolation and genotypic characterization of T. gondii in free-ranging
      striated heron, and the first genotypic characterization of T. gondii in a
      captive otter.

PMID- 30184005
TI  - Palliative care, amyotrophic lateral sclerosis, and swallowing: a case study.
AB  - This study aims to discuss Speech-language pathology (SLP) therapy intervention
      in dysphagia with a focus on palliative care and quality of life. It is a case
      study conducted with four participants with amyotrophic lateral sclerosis
      undergoing SLP therapy outpatient follow-up. The Swallowing Quality of Life
      Questionnaire (SWAL-QOL) and a structured interview were applied to the
      participants, who also underwent Videofluoroscopic Swallowing Study (VFSS).
      Participants were classified according to the Functional Oral Intake Scale
      (FOIS), the Amyotrophic Lateral Sclerosis Severity Scale, translated and
      culturally adapted to Brazilian Portuguese (ALSSS), and the Dysphagia Outcome
      Severity Scale (DOSS). Four patients showed interest in maintaining oral food
      intake, even if minimal, in the event of tube feeding. Regarding severity of
      dysphagia, observed in the SVF, the participants presented DOSS classification
      ranging from functional deglutition to mild-to-moderate dysphagia. The impact on
      swallowing quality of life was between discrete and severe. Not all participants
      presented correlation between severity of dysphagia and SWAL-QOL level of
      impairment, with impact on the quality of life observed even in cases of mild
      dysphagia severity. Participants reported that they would feel uncomfortable in
      the event of exclusive tube feeding, and that the oral intake of food, even if
      minimal only for the pleasure of eating, would have a direct or indirect impact
      on their quality of life.

PMID- 30184006
TI  - Efficacy of auditory training using the Programa de Escuta no Ruido (PER)
      software in students with auditory processing disorders and poor school
      performance.
AB  - PURPOSE: Investigate the efficacy of auditory training in students with auditory
      processing disorders and poor school performance using the software Programa de
      Escuta no Ruido (PER), which addresses auditory processing skills, specifically
      listening in noise. METHODS: Eighteen children aged 8-10 years, of both genders,
      participated in this study. All individuals participated in the following stages:
      pre-intervention assessment, intervention (consisting of placebo training, re
      evaluation of auditory processing, and auditory training), and post-intervention
      assessment, so that the same individual is self-control. RESULTS: No
      statistically significant difference was observed between the pre-intervention
      assessment and the post-training auditory processing re-evaluation of the
      placebo, but statistically significant difference was found between the pre- and
      post-auditory training conditions. CONCLUSION: The present study achieved its
      general objective. The PER software proved to be effective for the auditory
      training of students with auditory processing disorders and poor school
      performance.

PMID- 30184007
TI  - Transcranial direct current stimulation: a study on naming performance in aphasic
      individuals.
AB  - PURPOSE: Compare the results in naming tasks of after-stroke aphasic individuals
      divided into active and placebo groups pre- and post-transcranial direct current
      stimulation. METHODS: A double-blind, randomized, controlled study conducted with
      14 individuals. Patients underwent five 20-min sessions with stimulation of 2mA's
      on consecutive days. The cathode was placed over the Broca's homologous area and
      the anode was placed over the supraorbital region of the left hemisphere. Boston
      and Snodgrass naming tasks were assessed before and after the stimulation
      sessions and the results were compared between the groups. RESULTS: No
      significant results were observed for sequences 1 and 2 in the Snodgrass test.
      The Boston test results indicated significant difference related to mean time for
      correct responses with strategy. CONCLUSION: The results suggest that
      simultaneous transcranial direct current stimulation (anodic and cathodic) is a
      method that can improve the rehabilitation of patients with anomic and Broca's
      aphasia after stroke, and that language strategies should be considered in the
      analysis of naming task responses.

PMID- 30184009
TI  - Structural analysis of a fragmented area in Minas Gerais State, Brazil.
AB  - The theory of landscape ecology applied to the methods of spatial analysis helps
      to understand changes in the structure of forest remnants. In view of this
      theory, the objective of the present study was to analyze the structure of a
      fragmented area between the years 1979 and 2015 through calculation of landscape
      metrics for arboreal, shrubby and herbaceous vegetation classes. Vegetation
      classes were classified with visits to the field, interpretation of aerial
      photographs from 1979 and supervised classification of Landsat 8 from 2015. The
      metrics calculated for each class were area and total number of fragments, total
      edge and average connectivity among the fragments. The analysis of structure
      found that it changed negatively due to an increase in the number of small
      fragments, which increased the intensity of edge effects and reduced connectivity
      between fragments for all classes.

PMID- 30184008
TI  - Intake, apparent digestibility, rumen fermentation and nitrogen efficiency in
      sheep fed a tropical legume silage with or without concentrate.
AB  - Legume silage can increase the forage quality of the diets as well as supply it
      with nitrogen, calcium and phosphorus. The objective was to evaluate the intake,
      apparent digestibility, rumen fermentation and nitrogen efficiency in sheep fed a
      tropical legume silage with or without concentrate. Twelve crossbred sheep with
      an average initial body weight of 32.2 +/- 1.26 kg, with six animals cannulated
      in the rumen were distributed into four 3 * 3 Latin squares. The treatments were
      1) Stylosanthes silage without concentrate (StS), 2) Stylosanthes silage with
      concentrate (StS+C), and 3) corn silage with concentrate (CS+C). StS diet showed
      lowest intake, except for neutral detergent fiber (NDF). The diets StS+C and CS+C
      showed similar intake of dry matter (DM) and crude protein. The intake of total
      digestible nutrients was higher for CS+C diet than diets StS+C and StS. Animals
      fed CS+C diet had lowest ruminal pH. The nitrogen use efficiency was similar for
      the diets with concentrate. In conclusion, StS+C diet replacing CS+C diet
      decreases the intake of total digestible nutrients.

PMID- 30184010
TI  - Anatomical modifications of Butia capitata propagated under colored shade nets.
AB  - The jelly palm plant [Butia capitata (Martius) Beccari] is a native palm of the
      Cerrado biome used for many purposes in northern Minas Gerais State, Brazil.
      Dormancy is common in palm seeds, resulting in slow and uneven germination that
      may take years to complete. Modification in the growth pattern, anatomical
      parameters, physiological and biochemical characteristics of the plant can be
      verified due to changes in the light spectrum transmitted through colored shade
      nets used. Therefore, the objective of this study is to evaluate the effect of
      colored shade nets on the leaf and root anatomy of the jelly palm plant. The
      experiment was performed in a completely randomized design, with five treatments,
      ten replicates and eight plants per replicate, totaling 400 plants. Four colored
      photo-converter nets with 50% shading and different radiation proportions were
      employed: white (985 MUmol.m-2.s-1), red (327 MUmol.m-2.s-1), black (433 MUmol.m
      2.s-1) and silver (405 MUmol.m-2.s-1). The plants cultivated under direct
      sunlight (1000 MUmol.m-2.s-1) were considered as the control group. Leaf and root
      anatomical analysis was performed on 10 plants per treatment. It is possible to
      conclude that the colored shade nets caused changes in leaf and root anatomy of
      the jelly palm plant (Butia capitata).

PMID- 30184011
TI  - Fruits of the Brazilian Atlantic Forest: allying biodiversity conservation and
      food security.
AB  - Supplying food to growing human populations without depleting natural resources
      is a challenge for modern human societies. Considering this, the present study
      has addressed the use of native arboreal species as sources of food for rural
      populations in the Brazilian Atlantic Forest. The aim was to reveal species
      composition of edible plants, as well as to evaluate the practices used to manage
      and conserve them. Ethnobotanical indices show the importance of many native
      trees as local sources of fruits while highlighting the preponderance of the
      Myrtaceae family. Conservation analysis allowed to identify Campomanesia hirsuta
      Gardner and Plinia edulis (Vell.) Sobral as being of high Biological Value and
      Conservation Priority. In spite of that, the local management practices of native
      fruits appear to be sustainable and contribute to the maintenance and
      dissemination of valuable species. These results suggest a number of recommended
      future conservation actions and show the potential of Myrtaceae species for
      future agronomical development in Neotropical regions.

PMID- 30184012
TI  - Corn grain yield and 15N-fertilizer recovery as a function of urea sidedress
      timing.
AB  - Best fertilizer management practices such as adopting the right N sidedress
      timing can reduce N losses by volatilization, thus, raising N-fertilizer recovery
      and grain yield. To evaluate ammonia (N-NH3 ) losses, N-fertilizer recovery and
      grain yield as a function of urea sidedress timing in corn, a field study was
      conducted during the 2011-2012 and 2012-2013 growing seasons, adopting a complete
      randomized block design with four replications. Treatments consisted of urea
      sidedress timing (140 kg N ha-1) at V4, V6, V8, V10, and V12 growth stages, plus
      a control without sidedress N. The largest N losses by N-NH3 volatilization
      occurred when urea was applied at V10 or V12 growth stages, reaching losses of 35
      and 41 % of the total applied N. Although climatic factors influences N-NH3
      volatilization process, crop characteristics such as canopy development also
      seems to affect N-NH3 losses. Nitrogen application at V4 or V6 growth stages
      resulted in greater N-fertilizer recovery from urea sidedress, reaching values of
      53 %. No increase in corn grain yield was observed with N application at
      different corn growth stages during the two growing seasons evaluated, most
      likely due to high N mineralization rates from the soil.

PMID- 30184013
TI  - Morpho-physiological characteristics by sweet potato cultivars as function of
      irrigation depth.
AB  - The sweet potato is an alternative energy source, but its sustainability depends
      on efficient water use. The objective of this study was to evaluate sweet potato
      morpho-physiological characteristics, and water use efficiency (WUE). Irrigation
      depths of 50, 75, 100, and 125% of crop evapotranspiration (ETc) were applied.
      The morpho-physiological indicators, WUE, leaf area index (LAI), leaf water
      potential, leaf temperature, and leaf chlorophyll index (ICF), were evaluated.
      The WUE of the sweet potato cultivars increased until the 75% water depth of the
      ETc. The LAI of these cultivars increased with irrigation depth, with higher
      values at 100% of the ETc. The leaf water potential of the two sweet potato
      cultivars was lowest with the lower irrigation depth. Leaf temperature was closer
      to that of ambient temperatures in treatments with greater irrigation depth. The
      increase of the WUE with the greater accumulation of dry biomass is due to
      greater CO2 diffusion by stomata. The reduction in the growth of these plants is
      due to water stress limiting stomatal conductance, transpiration, leaf growth
      (LAI) and chlorophyll concentration, proportional to soil moisture conditions.
      The functional relationship between soil moisture and growth is essential to
      optimize irrigation management at different growth stages.

PMID- 30184014
TI  - Atrazine and nicosulfuron affect the reproductive fitness of the predator Podisus
      nigrispinus (Hemiptera: Pentatomidae).
AB  - Herbicides can impact non-target metabolic pathways in natural enemies and lead
      to the reduction of these populations in the field. Behavioral characteristics,
      morphology and histology of reproductive structures and reproduction of females
      of Podisus nigrispinus (Dallas) (Hemiptera: Pentatomidae) were evaluated under
      the effect of the herbicides atrazine, nicosulfuron and the mixture of both. The
      number of mature oocytes per ovary was lower in females exposed to the herbicides
      atrazine, nicosulfuron and the mixture of both. Herbicides did not affect the
      longevity and mortality of P. nigrispinus, therefore, they are selective for this
      predator. On the other hand, herbicides can cause sublethal effects by affecting
      the reproduction of predators.

PMID- 30184016
TI  - Technical efficiency analysis of marine shrimp farming (Litopenaeus vannamei) in
      biofloc and conventional systems: A case study in northeastern Brazil.
AB  - Shrimp farming has a great ecological, economic, and social importance in
      northeastern Brazil. Although the conventional farming system is widely used,
      biofloc technology (BFT) system has been developed to reduce environmental
      impacts and optimizing the production. Thus,the present study evaluated the
      technical efficiency of production cycles of Litopenaeus vannamei in conventional
      and BFT systems.We analyzed 48 production cycles in the conventional system in
      2013 and 2014 and 9 cycles in the BFT system in 2014 through data envelopment
      analysis (DEA). The inputs corresponded to the population density (post-larvae m
      2), amount of feed (kg ha-1 cycle-1), labor (man ha-1) and power supply (HP ha
      1), whereas the yield (kg ha-1 cycle-1) was considered the output. The results
      indicated four production cycles (7.0%) technically efficient, three in the
      conventional system and one in the BFT. By comparing the productive systems,
      there was significant difference in their mean scores of technical efficiency.
      There was a greater influence of the management inefficiency on the conventional
      system, while the production scale reduced the average scores of technical
      efficiency in the BFT system. These results may help to improve the development
      of sustainable L. vannamei farming in both systems by reducing waste and
      increasing profits.

PMID- 30184015
TI  - Volume equations for Khaya ivorensis A. Chev. plantations in Brazil.
AB  - African mahogany (Khaya spp.) plantations are in expansion in Brazil and in the
      world. This fact justifies the need for studies related to its growth and yield.
      This paper aimed to evaluate the performance of single-entry and double-entry
      models for estimating merchantable and total volume for Khaya ivorensis
      plantations before the first thinning (7 years) and expected final cut (15
      years). Volume data was from 100 and 46 trees in Minas Gerais and Para states,
      respectively, by using an electronic dendrometer (Criterion RD 1000). Observed
      volumes were calculated by Smalian's formula. To validate the optical
      dendrometer, 10 trees were felled and had their volume measured, and compared
      with the volumes measured indirectly. The results showed that observed and
      estimated volumes were statistically equal, and that double-entry models were
      more precise than single-entry models. Schumacher and Hall model was the best
      equation to estimate merchantable volume for first thinning and for final cut in
      Minas Gerais stands. Spurr logarithmized model was the best equation to estimate
      total volume for first thinning and Spurr model for final cut in Para stands. All
      chosen equations can be used to quantify merchantable and total volumes of Khaya
      ivorensis grown under similar conditions.

PMID- 30184017
TI  - Agronomic performance and genetic divergence between genotypes of Manihot
      esculenta.
AB  - The morphoagronomic characterization of 12 genotypes of M. esculenta was
      performed during the 2013/2014 and 2014/2015 crop years. The 12 genotypes were
      planted in a randomized block design, with four replicates per genotype. Number
      of tuberous roots per plant, weight of tuberous roots, root yield, total plant
      weight, harvest index, plant height, height of first branch, number of shoots,
      stem diameter, number of buds, leaf dry weight and petiole length were evaluated.
      Genotypes "Camuquem" and "Goias" were the most productive, and "Amarela" and
      "Gema de Ovo" were the most divergent. Seventy percent of genetic diversity was
      due to petiole length (22.86%), root yield (19.20%), weight of tuberous roots
      (14.89%) and number of buds (13.72%). Overall, the present results indicate a
      broad genetic basis for the evaluated genotypes, so that such genetic variation
      benefits the plant breeding for future scenarios Further studies of the evaluated
      genotypes should be performed under environmental limitations, using biochemical
      and molecular tools to identify markers for genetic improvement.

PMID- 30184018
TI  - [Conditioning factors for exclusive breastfeeding from the mother's perspective].
AB  - The study aimed to explore the positive and negative experiences of mothers with
      exclusive breastfeeding. A descriptive, qualitative study enrolled 18
      breastfeeding mothers of infants (<= 1 year) recruited in the Municipal
      Immunization Service in Vicosa, Minas Gerais State, Brazil. Data were obtained
      from taped, transcribed interviews and submitted to content analysis to verify
      the thematic units related to positive and negative experiences, after which two
      texts were drafted, one for each situation. These texts were submitted to
      similarity analysis with the IRAMUTEQ software, generating two similarity trees.
      Interpretation of the similarity trees used concordance lines produced by the
      AntConc software. The principal negative breastfeeding experiences were the
      infant's constant demand for the breast, the impossibility of leaving the infant
      alone, painful breasts, and insecurity concerning the capacity to produce enough
      milk. The main positive experiences were the biological benefits of breastmilk,
      practicality, and lower cost. The study allowed grasping the positive and
      negative dimensions of exclusive breastfeeding and suggests the importance of
      professional assistance for the woman in the initial phase of breastfeeding, plus
      social network support to mitigate the woman's overburdened feeling.

PMID- 30184019
TI  - [Validity of patient-reported anemia and therapeutic use of iron supplements
      during pregnancy: 2015 Pelotas (Brazil) birth cohort].
AB  - This study aimed to investigate the validity of patient-reported anemia and
      therapeutic use of iron supplements, compared to hemoglobin values recorded on
      the patient's prenatal card. The study used data from the 2015 Pelotas (Brazil)
      birth cohort. For validation of self-reported anemia, we included all mothers
      with hemoglobin values recorded on their prenatal card (N = 3,419), while
      validation of self-reported therapeutic use of iron supplements included those
      who had hemoglobin values recorded on their prenatal care and who reported having
      used medicines containing ferrous sulfate during pregnancy. Anemia was defined as
      at least one record of hemoglobin <= 11g/dL on the prenatal card (gold standard).
      Prevalence of anemia according to the gold standard was 35.9% (34.3-37.5), while
      patient-reported anemia was 42.2% (40.8-43.7), and patient-reported therapeutic
      use of iron supplements was 43.2% (41.3-45.1). Sensitivity of patient-reported
      anemia was 75.2% (72.8-77.6) and specificity was 75.1% (73.3-76.9). For patient
      reported therapeutic use of iron supplements, sensitivity was 66.4% (63.5-69.2)
      and specificity was 71.9% (69.7-74.0). Specificity of patient-reported anemia and
      patient-reported therapeutic use of iron supplements in mothers with >= 12 years
      of schooling was 78.4% (75.4-81.4) and 79.5% (76.1-82.9), respectively. In the
      study population, for every five postpartum women that reported anemia or
      therapeutic use of iron supplements, three were telling the truth. The
      specificity of both self-reports was high in mothers with >= 12 years of
      schooling.

PMID- 30184020
TI  - [Simulation and comparison of techniques for the correction of incomplete data on
      age to calculate incidence rates].
AB  - The objective was to compare two techniques to estimate age in databases with
      incomplete records and analyze their application to the calculation of cancer
      incidence. The study used the database of the Population-Based Cancer Registry
      from the city of Sao Paulo, Brazil, containing cases of urinary tract cancer
      diagnosed from 1997 to 2013. Two techniques were applied to estimate age:
      correction factor and multiple imputation. Using binomial distribution, six
      databases were simulated with different proportions of incomplete data on
      patient's age (from 5% to 50%). The ratio between the incidence rates was
      calculated, using the complete database as reference, whose standardized
      incidence was 11.83/100,000; the other incidence rates in the databases, with at
      least 5% incomplete data for age, were underestimated. By applying the correction
      factors, the corrected rates did not differ from the standardized rates, but this
      technique does not allow correcting specific rates. Multiple imputation was
      useful for correcting the standardized and specific rates in databases with up to
      30% of incomplete data, but the specific rates for individuals under 50 years of
      age were underestimated. Databases with 5% incomplete data or more require
      correction. Although the implementation of multiple imputation is complex, it
      proved to be superior to the correction factor. However, it should be used
      sparingly, since age-specific rates may remain underestimated.

PMID- 30184021
TI  - WATER INGESTION DYNAMICS IN PATIENTS WITH ACHALASIA: INFLUENCE OF SEX AND AGE.
AB  - BACKGROUND: Achalasia is a disease that affects esophageal bolus transit due to
      the absence of esophageal peristaltic contractions and impaired or absent
      relaxation of the lower esophageal sphincter. OBJECTIVE: The objective of this
      investigation was: a) to evaluate the dynamics of water ingestion in patients
      with achalasia, idiopathic or caused by Chagas' disease; b) to evaluate the
      influence of sex and age on water ingestion dynamics. METHODS: The investigation
      was conducted with 79 patients with achalasia (27 idiopathic and 52 Chagas'
      disease) and 91 healthy volunteers, all evaluated by the water-drinking test. The
      individuals drank, in triplicate, 50 mL of water without interruption. The time
      and the number of swallows for this task were counted. We also measured: (a)
      inter-swallow interval - the time to complete the task, divided by the number of
      swallows during the task; (b) swallowing rate - volume drunk divided by the time;
      (c) volume per swallow - volume drunk divided by the number of swallows. RESULTS:
      Patients with achalasia took longer to ingest all the volume (mean 12.2 seconds)
      than healthy controls (mean 5.4 seconds), had greater number of swallows, longer
      interval between swallows, lower swallowing rate (5.2 mL/s vs 10.9 mL/s in
      controls) and lower volume per swallow (9.1 mL vs 14.4 mL in controls, P<0.01).
      Among healthy volunteers, women had a shorter interval between swallows and lower
      volume per swallow compared with men, and in the achalasia group, women had a
      longer interval between swallows and lower ingestion rate. No difference in the
      drinking test results was found between younger and older subjects in achalasia
      or control group. Also, no differences were observed between patients with
      Chagas' disease and those with idiopathic achalasia, or between patients with
      increased and normal esophageal diameter. CONCLUSION: Patients with achalasia
      have difficulty in ingesting water, taking a longer time to complete the task,
      which is influenced by sex but not by age or severity of the disease.

PMID- 30184022
TI  - PROPOSALS TO APPROXIMATE THE PEDIATRIC ROME CONSTIPATION CRITERIA TO EVERYDAY
      PRACTICE.
AB  - BACKGROUND: Acceptance of the prevailing pediatric Rome constipation criteria, by
      primary care physician, is still low. Even for research purposes they have not
      been universally adopted. Thus, it has been indicated that some re-evaluation of
      these criteria would be welcome. OBJECTIVE: The authors aimed to look at the
      timing of diagnosis and the dietary treatment recommendations in the criteria, to
      make proposals trying to approximate them to everyday practice. METHODS: The
      literature cited in the Rome criteria was reviewed and the publications pertinent
      to the subject, searched by Medline up to January 2018, were included. RESULTS:
      An early diagnosis is fundamental to avoid evolution to bothersome complications
      and possibly to 'intractable' constipation, but the inclusion of two items of the
      criteria might hamper it. Thus, one constipation sign/symptom should suffice,
      usually the easily observable 'painful or hard bowel movements'. Details about
      dietary fiber recommendations are missing in the criteria, although its increase
      is usually the first approach in primary care, and overall the data about dietary
      fiber supplements point to beneficial effects. CONCLUSION: For diagnosis and
      treatment of pediatric constipation in primary care, one constipation
      sign/symptom should suffice. The recommended daily dietary fiber intake,
      according to the American Health Foundation, should be detailed as a treatment
      measure, and also for prevention, from weaning on.

PMID- 30184023
TI  - FUNCTIONAL CONSTIPATION AND OVERACTIVE BLADDER IN WOMEN: A POPULATION-BASED
      STUDY.
AB  - BACKGROUND: An association between urinary disorders and functional constipation
      has been registered in children and adults, with functional constipation being a
      common complaint in individuals with overactive bladder. OBJECTIVE: To evaluate
      the prevalence of functional constipation, overactive bladder and its dry/wet
      subtypes in women and to determine which bowel symptoms predict overactive
      bladder. METHODS: A cross-sectional study of women randomly approached in public
      spaces. Exclusion criteria: neurological/anatomical abnormalities of the bowel or
      urinary tract. Constipation was defined as >=2 positive symptoms of those listed
      in the Rome criteria. Urinary abnormalities (frequent urination, urgency,
      incontinence, nocturia) were defined by a score >=2 in the respective item of the
      International Consultation on Incontinence Questionnaire - Overactive Bladder.
      Dry overactive bladder was defined as urgency without incontinence, while wet
      overactive bladder included incontinence. RESULTS: A total of 516 women with a
      mean age of 35.8+/-6 years were interviewed. Rates of functional constipation,
      overactive bladder, dry overactive bladder and wet overactive bladder were 34.1%,
      15.3%, 8.9% and 6.4%, respectively. Functional constipation was associated with
      overactive bladder and dry overactive bladder, with functional constipation
      predicting dry overactive bladder (OR=2.47). Quality of life was poorer in
      constipated women compared to non-constipated and even worse in constipated women
      with wet overactive bladder (median 22.5; 95%CI: 17.25-35.25). Manual maneuvers
      were significantly associated with both overactive bladder subtypes. Independent
      predictive factors for overactive bladder were manual maneuvers (OR=2.21) and <3
      defecations/week (OR=2.18), with the latter being the only predictive factor for
      dry overactive bladder (OR=3.0). CONCLUSION: Functional constipation is
      associated with overactive bladder and its dry subtype, particularly in the
      younger population. In addition, this association is responsible for lower
      quality of life scores, especially when urinary incontinence is present. The
      presence of manual maneuvers and less than three defecations per week should
      direct us to look for overactive bladder.

PMID- 30184024
TI  - ?
AB  - [This corrects the article doi: 10.1590/S0004-2803.201800000-34].

PMID- 30184025
TI  - Is the Cardiopulmonary Bypass Systemic Inflammatory Response Overestimated?

PMID- 30184026
TI  - Operating with Data - Statistics for the Cardiovascular Surgeon: Part II.
      Association and Risk.

PMID- 30184027
TI  - Predictive Value of Mean Platelet Volume in Saphenous Vein Graft Disease.
AB  - OBJECTIVE: To determine whether mean platelet volume (MPV), platelet distribution
      width (PDW), and platelet count could be used as determinants of mortality
      following coronary artery bypass graft (CABG) surgery and patency of saphenous
      vein grafts (SVG). METHODS: The records of 128 patients who underwent emergency
      or elective coronary angiography after CABG surgery, and who died at an early
      stage were retrospectively reviewed. Patients were divided into three groups as
      early death, no SVG disease (SVGD), and SVGD group. MPV, PDW, and platelet count
      were evaluated at different times. RESULTS: MPV was significantly higher in the
      stenotic group than in the nonstenotic group (9.7+/-1.8 fl and 8.2+/-0.9 fl,
      P<0.05). The postoperative MPV ratio was found to be higher in the stenotic group
      when compared to the preoperative period (9.6+/-1.8 fl and 7.8+/-0.9 fl, P<0.05).
      MPV values were also found to be higher in patients who died during the early
      stage than in surviving patients (9.4+/-1.9 fl and 8.0+/-1.0 fl, P<0.05). There
      was no statistically significant difference regarding platelet count and PDW
      ratios between the early deaths group and surviving patients. An MPV value higher
      than 10.6 predicted SVGD with 85% sensitivity and 45% specificity; and an MPV
      higher than 7.9 predicted early death with 80% sensitivity and 68% specificity
      were observed. CONCLUSION: MPV may be a useful indicator for the prediction of
      SVGD and mortality following CABG surgery.

PMID- 30184028
TI  - Predictors of Postoperative Acute Kidney Injury after Coronary Artery Bypass
      Graft Surgery.
AB  - OBJECTIVE: The aims of this study were to identify the risk factors associated
      with acute kidney injury (AKI) after isolated surgical revascularization with
      cardiopulmonary bypass and to develop a model to predict the appearance of
      postoperative AKI. METHODS: A total of 435 adult patients who underwent primary
      isolated coronary artery bypass graft (CABG) surgery, from 2012 to 2016, in the
      Clinic University Hospital of Valladolid (Spain) were enrolled. AKI was defined
      according to the risk, injury, failure, loss, and end-stage (RIFLE) criteria.
      Data were collected from hospital electronic medical records. Multiple logistic
      regression analysis was used to identify risk factors. RESULTS: The prevalence of
      AKI was 12.4%. Multivariate analysis identified age (odds ratio [OR], 1.056; 95%
      confidence interval [CI], 1.016-1.098; P=0.005), hypertension (OR, 3.078; 95% CI,
      1.151-8.230; P=0.018), low ejection fraction (EF) (OR, 6.785; 95% CI, 2.080
      22.135; P=0.001), estimated glomerular filtration rate (eGFR) (OR, 1.017; 95% CI,
      1.005-1.028; P=0.014), EuroSCORE II (OR, 1.049; 95% CI, 1.004-1.096; P=0.033),
      and no intake of calcium-channel blockers (CCB) (OR, 4.892; 95% CI, 1.496-16.025;
      P=0.022) as risk factors for AKI. These risk factors were included in a model to
      predict postoperative AKI with an area under a receiver operating characteristic
      curve of 0.783+/-0.036 (95% CI, 0.713-0.854; P<0.0001). CONCLUSION: Age,
      hypertension, low EF, eGFR, EuroSCORE II, and no intake of CCB were independent
      risk factors for postoperative AKI. These factors provide an easy and accurate
      model to predict postoperative AKI in patients undergoing cardiac surgery.

PMID- 30184029
TI  - Is Preoperative Clopidogrel Resistance a Predictor of Bleeding and Risks in
      Patients Undergoing Emergency CABG Surgery?
AB  - OBJECTIVE: The aims of this study were to determine whether the detection of
      preoperative clopidogrel resistance in patients undergoing cardiac surgery while
      using clopidogrel could play a guiding role in the prediction of postoperative
      excessive bleeding, transfusion requirements, and risks and to provide clinically
      significant data. METHODS: Two hundred and twenty-two patients [median age: 59.4
      (38-83) years; 38 females] undergoing emergency and elective coronary artery
      bypass graft (CABG) surgeries in our clinic were evaluated prospectively.
      Patients with multiple systemic diseases, other than diabetes mellitus (DM) and
      hypertension (HT), were excluded. Patients receiving clopidogrel were also
      evaluated for clopidogrel resistance and grouped according to the results of this
      test. Assessments of platelet functions were performed by multiplate impedance
      aggregometry method and adenosine diphosphate test. RESULTS: The use of
      postoperative fresh blood replacement and platelet transfusion was higher in
      patients receiving clopidogrel than in those not receiving it (P=0.001, P=0.018).
      DM, HT, myocardial infarction, and the number of presentation to the emergency
      room were significantly higher in patients receiving clopidogrel than in those
      not receiving it (P<0.05). No significant difference was determined between
      patients with and without clopidogrel resistance regarding the amount of bleeding
      during and after surgery, erythrocyte suspension and fresh-frozen plasma
      transfusion rates, preoperative troponin values, ejection fraction values, and
      length of hospital stays (P>0.05). CONCLUSION: We think that resistance studies
      in patients receiving clopidogrel before cardiac surgery are not efficient to
      predict bleeding and bleeding-related complications in patients undergoing
      emergency and elective CABG surgeries.

PMID- 30184030
TI  - A Retrospective Survey Comparing Suture Techniques Regarding the Risk of
      Permanent Epicardial Pacemaker Implantation After Ventricular Septal Defect
      Closure.
AB  - OBJECTIVE: The aim of this study is to compare the continuous and combined
      suturing techniques in regards to the needing epicardial pacing at the time of
      weaning from cardiopulmonary bypass (EP-CPB) and to evaluate permanent epicardial
      pacemaker (PEP) implantation in patients who had undergone surgical ventricular
      septal defect (VSD) closure. METHODS: This single-centre retrospective survey
      includes 365 patients who had consecutively undergone VSD closure between January
      2006 and October 2015. RESULTS: The median age and weight of the patients were 15
      months (range 27 days - 56.9 years) and 10 kg (range 3.5 - 100 kg), respectively.
      Continuous and combined suturing techniques were utilised in 302 (82.7%) and 63
      (17.3%) patients, respectively. While 25 (6.8%) patients required EP-CPB, PEP was
      implanted in eight (2.2%) patients. Comparison of the continuous and combined
      suturing techniques regarding the need for EP-CPB (72% vs. 28%, P=0.231) and PEP
      implantation (87.5% vs. 12.5%, P=1.0) were not statistically significant. The
      rate of PEP implantation in patients with perimembraneous VSD without extension
      and perimembraneous VSD with inlet extension did not reveal significant
      difference between the suture techniques (P=1.0 and P=0.16, respectively). In
      both univariate and multivariate analyses, large VSD (P=0.001; OR 8.63; P=0.011)
      and perimembraneous VSD with inlet extension (P<0.001; OR 9.02; P=0.005) had a
      significant influence on PEP implantation. CONCLUSION: Both suturing techniques
      were comparable regarding the need for EP-CPB or PEP implantation. Caution should
      be exercised when closing a large perimembraneous VSD with inlet extension.

PMID- 30184031
TI  - Preventive Effect of Preoperative Vitamin D Supplementation on Postoperative
      Atrial Fibrillation.
AB  - OBJECTIVE: To assess the relationship between preoperative vitamin D (vitD)
      supplementation and the development of postoperative atrial fibrillation (POAF).
      METHODS: The study group consisted of 328 consecutive patients. The influence of
      preoperative vitD supplementation on POAF was reviewed in 136 patients who
      underwent coronary artery bypass graft surgery with vitD insufficiency (n=80) and
      vitD deficiency (n=56). Patients were assigned to receive either oral vitD
      (50.000 U) (treatment group, n=68) or not (control group, n=68) 48 hours before
      surgery. Patients were followed up during hospitalisation process with respect to
      POAF. RESULTS: There was no significant difference between treatment and control
      groups with regards to age, gender, diabetes mellitus, smoking history, chronic
      obstructive pulmonary disease, left atrial diameter, and biochemical parameters.
      Also, there was no significant difference between these groups with regards to
      mean vitD level on both insufficiency and deficiency patients (24.6+/-3.7 vs.
      24.9+/-3.9 ng/ml P=0.837, 11.4+/-4.9 vs. 10.9+/-5.2 ng/ml P=0.681, respectively).
      Although the occurrence of POAF was not significantly different among treatment
      and control groups in patients with vitD insufficiency (31% vs. 33% P=0.538),
      there was a significant difference between the two groups regarding to POAF in
      patients with vitD deficiency (18% vs. 29% P=0.02). CONCLUSION: Although
      preoperative vitD supplementation was not found to be associated with prevention
      of POAF in patients with vitD insufficiency, it was found to be strongly
      associated with prevention of POAF in those with vitD deficiency.

PMID- 30184032
TI  - Ebstein's Anomaly: "The One and a Half Ventricle Heart".
AB  - OBJECTIVE: Ebstein's anomaly remains a relatively ignored disease. Lying in the
      'No Man's land' between congenital and valve surgeons, it largely remains
      inadequately studied. We report our short-term results of treating it as a 'one
      and a half ventricle heart' and propose that the true tricuspid annulus (TTA) 'Z'
      score be used as an objective criterion for estimation of 'functional' right
      ventricle (RV). METHODS: 22 consecutive patients undergoing surgery for Ebstein's
      anomaly were studied. Echocardiography was performed to assess the type and
      severity of the disease, tricuspid annular dimension and its 'Z' score. Patients
      were operated by a modification of the cone repair, with addition of
      annuloplasty, bidirectional cavopulmonary shunt (BCPS) and right reduction
      atrioplasty to provide a comprehensive repair. TTA 'Z' score was correlated later
      with postplication indexed residual RV volume. RESULTS: There was one (4.5%)
      early and no late postoperative death. There was a significant reduction in
      tricuspid regurgitation grading (3.40+/-0.65 to 1.22+/-0.42, P<0.001). Residual
      RV volume reduced to 71.96+/-3.8% of the expected volume and there was a
      significant negative correlation (rho -0.83) between TTA 'Z' score and indexed
      residual RV volume. During the follow-up of 20.54+/-7.62 months, the functional
      class improved from 2.59+/-0.7 to 1.34+/-0.52 (P<0.001). CONCLUSION: In Ebstein's
      anomaly, a higher TTA 'Z' score correlates with a lower postplication indexed
      residual RV volume. Hence, a complete trileaflet repair with offloading of RV by
      BCPS (when the TTA 'Z' score is >2) is recommended. The short-term outcomes of
      our technique are promising.

PMID- 30184033
TI  - Thrombocytopenia After Transcatheter Valve-in-Valve Implantation: Prognostic
      Marker or Mere Finding?
AB  - OBJECTIVE: To analyze the behavior of platelets after transcatheter valve-in
      valve implantation for the treatment of degenerated bioprosthesis and how they
      correlate with adverse events upon follow-up. METHODS: Retrospective analysis of
      28 patients who received a valve-in-valve implant, 5 in aortic, 18 in mitral and
      5 in tricuspid positions. Data were compared with 74 patients submitted to
      conventional redo valvular replacements during the same period, and both groups'
      platelet curves were analyzed. Statistical analysis was conducted using the IBM
      SPSS Statistics(r) 20 for Windows. RESULTS: All patients in the valve-in-valve
      group developed thrombocytopenia, 25% presenting mild (<150.000/uL), 54% moderate
      (<100.000/uL) and 21% severe (<50.000/uL) thrombocytopenia. The platelet nadir
      was on the 4th postoperative day for aortic ViV, 2nd for mitral and 3rd for
      tricuspid patients, with the majority of patients recovering regular platelet
      count. However, the aortic subgroup comparison between valve-in-valve and
      conventional surgery showed a statistically significant difference from the 7th
      day onwards, where valve-in-valve patients had more severe and longer lasting
      thrombocytopenia. This, however, did not translate into a higher postoperative
      risk. In our study population, postoperative thrombocytopenia did not correlate
      with greater occurrence of adverse outcomes and only normal preoperative platelet
      count could significantly predict a postoperative drop >50%. CONCLUSION: Although
      thrombocytopenia is an extremely common finding after valve-in-valve procedures,
      the degree of platelet count drop did not correlate with greater incidence of
      postoperative adverse outcomes in our study population.

PMID- 30184035
TI  - Effects of High-Intensity Inspiratory Muscle Training Associated with Aerobic
      Exercise in Patients Undergoing CABG: Randomized Clinical Trial.
AB  - OBJECTIVE: Evaluate the interaction between high-intensity inspiratory muscle
      training (IMT) and aerobic exercise on physical capacity, respiratory muscle
      strength, peripheral muscle strength, and quality of life of patients who
      underwent coronary artery bypass grafting (CABG). METHODS: Twenty-four patients
      underwent CABG were randomized into two groups. During 36 sessions, one group
      received IMT associated with aerobic exercise and the other group received only
      aerobic exercise. Primary outcome was the distance in the six-minute walk
      distance (6MWD) test. Secondary outcomes included respiratory muscle strength,
      peripheral muscle strength, and quality of life. Measures were taken at the
      baseline, at the 12th session, the 24th session, and 36th session. RESULTS:
      Baseline characteristics were similar between the groups. There was no
      statistically significant difference between the two groups in any outcome [6MWD 
      P=0.935; peak oxygen consumption (PeakVO2) - P=0.853; maximal inspiratory
      pressure (MIP) - P=0.243; maximal expiratory pressure (MEP) - P=0.268; sitting
      rising test (SRT) - P=0.212], but there was interaction in MIP (P=0.000) and all
      outcomes improved in the two groups (6MWD - P=0.000; PeakVO2 - P=0.000; MIP -
      P=0.000; MEP - P=0.000; SRT - P=0.000). CONCLUSION: There was an improvement of
      all outcomes in both groups, but IMT was not able to provide additional benefits.
      The use of this combination should be used with caution to not generate higher
      costs in the rehabilitation process of these patients.

PMID- 30184034
TI  - Incidence of Nausea and Vomiting After Fast-Track Anaesthesia for Heart Surgery.
AB  - OBJECTIVE: The aim of this study was to evaluate the incidence of postoperative
      nausea and vomiting (PONV) after fast-track cardiac anesthesia (FTCA) in the
      first 24-48 hours in the cardiac intensive care unit (CICU) after open-heart
      surgery, risk factors for PONV and its influence on CICU length of stay. METHODS:
      A prospective observational study from January 1, 2013 to the end of December
      2015 was performed in the CICU of a university hospital in the north of Jordan
      and Queen Alia Heart Institute, Amman, Jordan. Three hundred consecutive patients
      undergoing fast-track cardiac anesthesia in elective cardiac surgery were
      enrolled in the study. Nausea and vomiting were assessed after tracheal
      extubation, which was performed within 6-10 hours after surgery and during the
      first 24-48 hours in the CICU. Metoclopramide 10 mg intravenously was used as the
      initial antiemetic drug, but ondansetron 4 mg intravenously was also used as
      second line of management. RESULTS: Nausea was reported in 46 (15.3%) patients,
      and vomiting in 31 (10.3%). Among females, 38 (33.9%) patients developed nausea
      and 20 (17.9%) developed vomiting. Among males, 8 (4.3%) patients developed
      nausea and 11 (5.9%) developed vomiting. CONCLUSION: PONV are relatively low
      after FTCA and the prophylactic administration of antiemetic drug before
      anesthesia or after extubation is not necessary.

PMID- 30184036
TI  - Protective Effects of Baicalin on Experimental Myocardial Infarction in Rats.
AB  - OBJECTIVE: This study aimed to investigate the protective effects of baicalin on
      myocardial infarction in rats and explore the related mechanisms. METHODS: Fifty
      Sprague Dawley rats were randomly divided into the control, model, and low-,
      medium- and high-dose baicalin groups. The latter 3 groups were intraperitoneally
      injected with baicalin, with a dose of 12.5, 25 and 50 mg/kg, respectively. Then,
      the myocardial infarction model was established. The hemodynamic of rats was
      tested, the serum lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB),
      prostacyclin (PGI2) and thromboxane A2 (TXA2) were determined, the myocardial
      superoxide dismutase (SOD) and malondialdehyde (MDA) levels were detected, and
      the myocardial B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X (Bax) protein
      expressions were determined. RESULTS: Compared with the model group, in the high
      dose baicalin group the ST segment height and LVEDP were significantly decreased
      (P<0.05), the LVSP was significantly increased (P<0.05), the serum LDH, CK-MB and
      TXA2 levels were significantly decreased (P<0.05), the PGI2 level was
      significantly increased (P<0.05), the myocardial SOD level was significantly
      increased (P<0.05), and the myocardial MDA level was significantly decreased
      (P<0.05); the myocardial Bcl-2 protein level was significantly increased, and the
      Bax protein level was significantly decreased (P<0.05). CONCLUSION: Baicalin has
      protective effects on myocardial infarction in rats. The possible mechanisms may
      be related to its resistance to oxidative stress, and up-regulation of Bcl-2
      protein expression and down-regulation of Bax protein expression in myocardial
      tissue.

PMID- 30184037
TI  - Development and Application of a System Based on Artificial Intelligence for
      Transcatheter Aortic Prosthesis Selection.
AB  - INTRODUCTION: The interest in Expert systems has increased in the medical area.
      Some of them are employed even for diagnosis. With the variability of
      transcatheter prostheses, the most appropriate choice can be complex. This
      scenario reveals an enabling environment for the use of an Expert system. The
      goal of the study was to develop an Expert system based on artificial
      intelligence for supporting the transcatheter aortic prosthesis selection.
      METHODS: The system was developed on Expert SINTA. The rules were created
      according to anatomical parameters indicated by the manufacturing company.
      Annular aortic diameter, aortic area, aortic perimeter, ascending aorta diameter
      and Valsalva sinus diameter were considered. After performing system accuracy
      tests, it was applied in a retrospective cohort of 22 patients with submitted to
      the CoreValve prosthesis implantation. Then, the system indications were compared
      to the real heart team decisions. RESULTS: For 10 (45.4%) of the 22 patients
      there was no concordance between the Expert system and the heart team. In all
      cases with discordance, the software was right in the indication. Then, the
      patients were stratified in two groups (same indication vs. divergent
      indication). The baseline characteristics did not show any significant
      difference. Mortality, stroke, acute myocardial infarction, atrial fibrillation,
      atrioventricular block, aortic regurgitation and prosthesis leak did not present
      differences. Therefore, the maximum aortic gradient in the post-procedure period
      was higher in the Divergent Indication group (23.9 mmHg vs. 11.9 mmHg, P=0.03),
      and the mean aortic gradient showed a similar trend. CONCLUSION: The utilization
      of the Expert system was accurate, showing good potential in the support of
      medical decision. Patients with divergent indication presented high post
      procedure aortic gradients and, even without clinical repercussion, these
      parameters, when elevated, can lead to early prosthesis dysfunction and the
      necessity of reoperation.

PMID- 30184038
TI  - Quadruple Valve Replacement for Carcinoid Heart Disease.
AB  - INTRODUCTION: Carcinoid heart disease most frequently involves the tricuspid or,
      more rarely, the pulmonary valve and presents with right heart failure as 5-HT is
      metabolized by the lung. Left-sided valve involvement is quite rare. We describe
      our experience of 3 patients presenting with heart failure secondary to carcinoid
      heart disease affecting all four cardiac valves. There are only four previous
      isolated case reports in the literature. METHODS: All three patients underwent
      quadruple valve replacement during a single operation. Right ventricular outflow
      tract reconstruction with a pericardial patch was performed in all patients. For
      24 hours prior to surgery, all patients received intravenous octreotide, which
      continued in intensive care for at least 24 hours. RESULTS: Mean cross-clamp and
      bypass times were 175 (range 164-197 minutes) and 210 (range 195-229 minutes)
      minutes, respectively. Mean intensive treatment unit (ITU) and inpatient stays
      were 2.3 (range 2-3 days) and 12 (range 9-16 days) days, respectively. One
      patient was reopened for bleeding 4 hours postoperatively from a ventricular
      pacing wire site. None required a permanent pacemaker postoperatively. There were
      no other complications in any patient. The quality of life was excellent at 6-16
      months clinic follow-up as they were in NYHA 1. Postoperative echocardiography
      showed no paravalvular leaks and well-functioning prostheses in all cases.
      CONCLUSION: Surgery to replace all four valves is feasible with excellent medium
      term survival and a very low rate of complications. Patients with carcinoid heart
      disease should always be considered for surgery irrespective of the extent of
      valvular involvement.

PMID- 30184039
TI  - The Effect of Dexmedetomidine on the Acute Pain After Cardiothoracic Surgeries: A
      Systematic Review.
AB  - INTRODUCTION: Acute post-operative pain remains a troublesome complication of
      cardiothoracic surgeries. Several randomized controlled trials have examined the
      efficacy of dexmedetomidine as a single or as an adjuvant agent before, during
      and after surgery. However, no evidence-based conclusion has been reached
      regarding the advantages of dexmedetomidine over the other analgesics. OBJECTIVE:
      To review the effect of dexmedetomidine on acute post-thoracotomy/sternotomy
      pain. METHODS: Medline, SCOPUS, Web of Science, and Cochrane databases were used
      to search for randomized controlled trials that investigated the analgesia effect
      of dexmedetomidine on post-thoracotomy/sternotomy pain in adults' patients. The
      outcomes were postoperative pain intensity or incidence, postoperative analgesia
      duration, and the number of postoperative analgesic requirements. RESULTS: From
      1789 citations, 12 trials including 804 subjects met the inclusion criteria. Most
      studies showed that pain score was significantly lower in the dexmedetomidine
      group up to 24 hours after surgery. Two studies reported the significant lower
      postoperative analgesia requirements and one study reported the significant lower
      incidence of acute pain after surgery in dexmedetomidine group. Ten studies found
      that the total consumption of narcotics was significantly lower in the
      dexmedetomidine group. The most reported complications of dexmedetomidine were
      nausea/vomiting, bradycardia and hypotension. CONCLUSION: Dexmedetomidine can be
      used as a safe and efficient analgesic agent for reducing the postoperative pain
      and analgesic requirements up to 24 hours after cardiothoracic surgeries.
      However, further well-designed trials are needed to find the optimal dosage,
      route, time, and duration of dexmedetomidine administration.

PMID- 30184040
TI  - Successful Treatment of Ventricular Arrhythmia in Tetralogy of Fallot Repair
      Using Catheter Ablation.
AB  - Tetralogy of Fallot (ToF) is one of the most prevalent congenital heart disease.
      Its surgical corrections may haemodinamically correct a disease, but the
      incisions may create scars that will originate ventricular arrhythmias. Even
      though life threatening arrhythmias are not common, some patients present
      unstable ventricular tachycardia (VT) of ectopic ventricular beats triggering
      heart failure and symptoms. We describe the treatment of a 16-years-old woman
      with late ToF repair and drug refractory Implantable cardioverter defibrillator
      (ICD) shocks. The patient underwent successful ablation of VT using X-ray and
      anatomic landmarks without the use of electroanatomical mapping. We were able to
      reduce drugs after one month of ablation and improve quality of life and
      symptoms. In this paper we describe the indications and perform a brief review of
      the key points for successful radiofrequency catheter ablation of VT in ToF
      patients.

PMID- 30184041
TI  - Surgical Repair of Complex Aortopulmonary Window: A Case Study.
AB  - Aortopulmonary septal defect, also known as the aortopulmonary window, is a rare
      congenital macrovascular malformation. This case involves a 9-year-old boy with
      aortopulmonary septal defect (type I combined with type IV). Before surgery,
      milrinone and alprostadil were used to counteract high lung pressure. Surgery was
      performed under cardiopulmonary bypass, following which the pulmonary pressure
      decreased. The aorta was cut, and the right pulmonary artery opening was
      connected with the main pulmonary artery septal defect using polyester patch. An
      internal tunnel was made, and the deformity correction was completed. The child
      exhibited normal postoperative recovery with no discomfort. A complex
      aortopulmonary window is a rare condition that can be treated successfully with
      appropriate preoperative and surgical management.

PMID- 30184042
TI  - How International Internships Enrich a Medical Career.

PMID- 30184043
TI  - Breast cancer prognosis signature: linking risk stratification to disease
      subtypes.
AB  - Breast cancer is a very complex and heterogeneous disease with variable molecular
      mechanisms of carcinogenesis and clinical behaviors. The identification of
      prognostic risk factors may enable effective diagnosis and treatment of breast
      cancer. In particular, numerous gene-expression-based prognostic signatures were
      developed and some of them have already been applied into clinical trials and
      practice. In this study, we summarized several representative gene-expression
      based signatures with significant prognostic value and separately assessed their
      ability of prognosis prediction in their originally targeted populations of
      breast cancer. Notably, many of the collected signatures were originally designed
      to predict the outcomes of estrogen receptor positive (ER+) patients or the whole
      breast cancer cohort; there are no typical signatures used for the prognostic
      prediction in a specific population of patients with the intrinsic subtype. We
      thus attempted to identify subtype-specific prognostic signatures via a
      computational framework for analyzing multi-omics profiles and patient survival.
      For both the discovery and an independent data set, we confirmed that subtype
      specific signature is a strong and significant independent prognostic factor in
      the corresponding cohort. These results indicate that the subtype-specific
      prognostic signature has a much higher resolution in the risk stratification,
      which may lead to improved therapies and precision medicine for patients with
      breast cancer.

PMID- 30184044
TI  - When a Single Lineage Is Not Enough: Uncertainty-Aware Tracking for Spatio
      Temporal Live-Cell Image Analysis.
AB  - Motivation: Microfluidic platforms for live-cell analysis are in dire need of
      automated image-analysis pipelines. In this context, producing reliable tracks of
      single cells in colonies has proven to be notoriously difficult without manual
      assistance, especially when image sequences experience low frame rates. Results:
      With Uncertainty-Aware Tracking (UAT), we propose a novel probabilistic tracking
      paradigm for simultaneous tracking and estimation of tracking-induced errors in
      biological quantities derived from live-cell experiments. To boost tracking
      accuracy, UAT relies on a Bayesian approach which exploits temporal information
      on growth patterns to guide the formation of lineage hypotheses. A biological
      study is presented, in which UAT demonstrates its ability to track cells, with
      comparable to better accuracy than state-of-the-art trackers, while
      simultaneously estimating tracking-induced errors. Availability: Image sequences
      and Java executables for reproducing the results are available at
      https://doi.org/10.5281/zenodo.1299526.

PMID- 30184045
TI  - Deconvoluting essential gene signatures for cancer growth from genomic expression
      in compound-treated cells.
AB  - Motivation: Essential gene signatures for cancer growth have been typically
      identified via RNAi or CRISPR-Cas9. Here, we propose an alternative method that
      reveals the essential gene signatures by analysing genomic expression profiles in
      compound-treated cells. With a large amount of the existing compound-induced
      data, essential gene signatures at genomic scale are efficiently characterized
      without technical challenges in the previous techniques. Results: An essential
      gene is characterized as a gene presenting positive correlation between its down
      regulation and cell growth inhibition induced by diverse compounds, which were
      collected from LINCS and CGP. Among 12,741 genes, 1,092, 1,228, 827, 962, 1,664,
      580 and 829 essential genes are characterized for each of A375, A549, BT20,
      LNCAP, MCF7, MDAMB231 and PC3 cell lines (p-value <= 1.0E-05). Comparisons to the
      previously identified essential genes yield significant overlaps in A375 and A549
      (p-value <= 5.0E-05), and the 103 common essential genes are enriched in crucial
      processes for cancer growth. In most comparisons in A375, MCF7, BT20 and A549,
      the characterized essential genes yield more essential characteristics than those
      of the previous techniques, i.e. high gene expression, high degrees of protein
      protein interactions, many homologs and few paralogs. Remarkably, the essential
      genes commonly characterized by both the previous and proposed techniques show
      more significant essential characteristics than those solely relied on the
      previous techniques. We expect that this work provides new aspects in essential
      gene signatures. Availability and implementation: The Python implementations are
      available at
      https://github.com/jmjung83/deconvolution_of_essential_gene_signitures.
      Supplementary information: Supplementary information is available at
      bioinformatics online.

PMID- 30184046
TI  - SCOP: a novel scaffolding algorithm based on contig classification and
      optimization.
AB  - Motivation: Scaffolding is an essential step during the de novo sequence assembly
      process to infer the direction and order relationships between the contigs and
      make the sequence assembly results more continuous and complete. However,
      scaffolding still faces the challenges of repetitive regions in genome,
      sequencing errors, and uneven sequencing depth. Moreover, the accuracy of
      scaffolding greatly depends on the quality of contigs. Generally, the existing
      scaffolding methods construct a scaffold graph, and then optimize the graph by
      deleting spurious edges. Nevertheless, due to the wrong joints between contigs,
      some correct edges connecting contigs may be deleted. Results: In this study, we
      present a novel scaffolding method SCOP, which is the first method to classify
      the contigs and utilize the vertices and edges to optimize the scaffold graph.
      Specially, SCOP employs alignment features and GC-content of paired reads to
      evaluate the quality of contigs (vertices), and divide the contigs into three
      types (True, Uncertain, and Misassembled), and then optimizes the scaffold graph
      based on the classification of contigs together with the alignment of edges. The
      experiment results on the datasets of GAGE-A and GAGE-B demonstrate that SCOP
      performs better than twelve other competing scaffolders. Availability and
      Implementation: SCOP is publicly available for download at
      https://github.com/bioinfomaticsCSU/SCOP. Supplementary information:
      Supplementary data are available at Bioinformatics online.

PMID- 30184047
TI  - metaGraphite - a new layer of pathway annotation to get metabolite networks.
AB  - Motivation: Metabolomics is an emerging 'omics' science involving the
      characterization of metabolites and metabolism in biological systems. Few
      bioinformatic tools have been developed for the visualization, exploration and
      analysis of metabolomic data within the context of metabolic pathways: some of
      them became rapidly obsolete and are no longer supported, others are based on a
      single database. A systematic collection of existing annotations has the
      potential of considerably boosting the investigation and contextualization of
      metabolomic measurements. Results: We have released a major update of our
      Bioconductor package graphite which explicitly tracks small molecules within
      pathway topologies and their interactions with proteins. The package gathers the
      information stored in eight major databases, oriented both at genes and at
      metabolites, across 14 different species. Depending on user preferences, all
      pathways can be retrieved as gene-only, gene-metabolite or metabolite-only
      networks. Availability: The new graphite version (1.24) is available on
      Bioconductor. Supplementary information: Supplementary data are available at
      Bioinformatics online and at the BioConductor repository.

PMID- 30184048
TI  - Precision Lasso: Accounting for Correlations and Linear Dependencies in High
      Dimensional Genomic Data.
AB  - Motivation: Association studies to discover links between genetic markers and
      phenotypes are central to bioinformatics. Methods of regularized regression, such
      as variants of the Lasso, are popular for this task. Despite the good predictive
      performance of these methods in the average case, they suffer from unstable
      selections of correlated variables and inconsistent selections of linearly
      dependent variables. Unfortunately, as we demonstrate empirically, such
      problematic situations of correlated and linearly dependent variables often exist
      in genomic data sets and lead to under-performance of classical methods of
      variable selection. Results: To address these challenges, we propose the
      Precision Lasso. Precision Lasso is a Lasso variant that promotes sparse variable
      selection by regularization governed by the covariance and inverse covariance
      matrices of explanatory variables. We illustrate its capacity for stable and
      consistent variable selection in simulated data with highly correlated and
      linearly dependent variables. We then demonstrate the effectiveness of the
      Precision Lasso to select meaningful variables from transcriptomic profiles of
      breast cancer patients. Our results indicate that in settings with correlated and
      linearly dependent variables, the Precision Lasso outperforms popular methods of
      variable selection such as the Lasso, the Elastic Net, and Minimax Concave
      Penalty (MCP) regression. Availability: Software is available at
      https://github.com/HaohanWang/thePrecisionLasso. Supplementary information:
      Supplementary data are available at Bioinformatics online.

PMID- 30184049
TI  - AGILE: an assembled genome mining pipeline.
AB  - Summary: A number of limiting factors mean that traditional genome annotation
      tools either fail or perform sub-optimally when trying to detect coding sequences
      in poor quality genome assemblies/genome reports. This means that potentially
      useful data is accessible only to those with specific skills and expertise in
      assembly and annotation. We present an Assembled-Genome mInig pipeLinE (AGILE)
      written in Perl that combines bioinformatics tools with a number of steps to
      overcome the limitations imposed by such assemblies when applied to highly
      fragmented genomes. Our methodology uses user specified query genes from a
      closely related species to mine and annotate coding sequences that would
      traditionally be missed by standard annotation packages. Despite a focus on
      mammalian genomes, the generalized implementation means that it may be applied to
      any genome assembly, providing a means for non-specialists to gather gene
      sequences for downstream analyses. Availability: Source code and associated files
      are available at: https://github.com/batlabucd/GenomeMining and
      https://bitbucket.org/BatlabUCD/genomemining/src. Singularity and Virtual Box
      images available at https://figshare.com/s/a0004bf93dc43484b0c0. Supplementary
      information: Supplementary data are available at bioinformatics online.

PMID- 30184050
TI  - Bracket slot size selection: after all a matter of taste?
AB  - The publication of the three-paper series on the effects of two slot sizes on
      treatment parameters in this issue, targets a topic, which has attracted a lot of
      discussion based primarily on anecdotal evidence. The conclusive evidence
      contribute to the lack of variation of treatment variables with slot size
      selection, clarifies one of the traditional beliefs on this issue; several others
      still hold strong however. This commentary has the objective of highlighting some
      points, which could be taken into consideration in interpreting the results of
      this three-part trial.

PMID- 30184051
TI  - Differential Methylation Values in Differential Methylation Analysis.
AB  - Motivation: Both beta-value and M-value have been used as metrics to measure
      methylation levels. The M-value is more statistically valid for the differential
      analysis of methylation levels. However, the beta-value is much more biologically
      interpretable and needs to be reported when M-value method is used for conducting
      differential methylation analysis. There is an urgent need to know how to
      interpret the degree of differential methylation from the M-value. In M-value
      linear regression model, differential methylation M-value DeltaM can be easily
      obtained from the coefficient estimate, but it is not straightforward to get the
      differential methylation beta-value, Deltabeta since it cannot be obtained from
      the coefficient alone. Results: To fill the gap, we have built a bridge to
      connect the statistically sound M-value linear regression model and the
      biologically interpretable Deltabeta. In this paper, 3 methods were proposed to
      calculate differential methylation values, Deltabeta from M-value linear
      regression model and compared with the Deltabeta directly obtained from beta
      value linear regression model. We showed that under the condition that M-value
      linear regression model is correct, the method M-model-coef is the best among the
      four methods. M-model-M-mean method works very well too. If the coefficients
      alpha0, alpha2,...alphap are not given (as "MethLAB" package [Kilaru et al.
      2012]), the M-model-M-mean method should be used. The Deltabeta directly obtained
      from beta-value linear regression model can give very biased results, especially
      when M-values are not in (-2, 2) or beta-values are not in (0.2, 0.8).
      Availability: The dataset for example is available at the National Center for
      Biotechnology Information Gene Expression Omnibus repository, GSE104778.
      Supplementary information: Supplementary data are available at Bioinformatics
      online.

PMID- 30184052
TI  - DeepGSR: An optimized deep-learning structure for the recognition of genomic
      signals and regions.
AB  - Motivation: Recognition of different genomic signals and regions (GSRs) in DNA is
      crucial for understanding genome organization, gene regulation, and gene
      function, which in turn generate better genome and gene annotations. Although
      many methods have been developed to recognize GSRs, their pure computational
      identification remains challenging. Moreover, various GSRs usually require a
      specialized set of features for developing robust recognition models. Recently,
      deep-learning (DL) methods have been shown to generate more accurate prediction
      models than 'shallow' methods without the need to develop specialized features
      for the problems in question. Here, we explore the potential use of DL for the
      recognition of GSRs. Results: We developed DeepGSR, an optimized DL architecture
      for the prediction of different types of GSRs. The performance of the DeepGSR
      structure is evaluated on the recognition of polyadenylation signals (PAS) and
      translation initiation sites (TIS) of different organisms: human, mouse, bovine,
      and fruit fly. The results show that DeepGSR outperformed the state-of-the-art
      methods, reducing the classification error rate of the PAS and TIS prediction in
      the human genome by up to 29% and 86%, respectively. Moreover, the cross
      organisms and genome-wide analyses we performed, confirmed the robustness of
      DeepGSR and provided new insights into the conservation of examined GSRs across
      species. Availability and implementation: DeepGSR is implemented in Python using
      Keras API; it is available as open-source software and can be obtained at
      https://doi.org/10.5281/zenodo.1117159?. Supplementary information: Supplementary
      data are available at Bioinformatics online.

PMID- 30184053
TI  - Effects of Leptin on the Skeleton.
AB  - Leptin originates in adipocytes, including those in bone marrow, and circulates
      in concentrations 20 to 90 times higher than those in the cerebrospinal fluid. It
      has direct anabolic effects on osteoblasts and chondrocytes, but it also
      influences bone indirectly, via the hypothalamus and sympathetic nervous system,
      via changes in body weight, and via effects on the production of other hormones
      (e.g., pituitary). Leptin's role in bone physiology is determined by the balance
      of these conflicting effects. Reflecting this inconsistency, the leptin-deficient
      mouse has reduced length and bone mineral content of long bones but increased
      vertebral trabecular bone. A consistent bone phenotype in human leptin deficiency
      has not been established. Systemic leptin administration in animals and humans
      usually exerts a positive effect on bone mass, and leptin administration into the
      cerebral ventricles usually normalizes the bone phenotype in leptin-deficient
      mice. Reflecting the role of the sympathetic nervous system in mediating the
      central catabolic effects of leptin on the skeleton, beta-adrenergic agonists and
      antagonists have major effects on bone in mice, but this is not consistently seen
      in humans. The balance of the central and peripheral effects of leptin on bone
      remains an area of substantial controversy and might vary between species and
      according to other factors such as body weight, baseline circulating leptin
      levels, and the presence of specific pathologies. In humans, leptin is likely to
      contribute to the positive relationship observed between adiposity and bone
      density, which allows the skeleton to respond appropriately to changes in soft
      tissue mass.

PMID- 30184054
TI  - The octopus on a heart.

PMID- 30184055
TI  - Glutton: A tool for generating structural ensembles of partly disordered proteins
      from chemical shifts.
AB  - Motivation: Many proteins are partially disordered in physiological conditions
      and only fold, fully or partially, upon binding. Their structural analysis is
      challenging because the accessible information, typically chemical shifts from
      nuclear magnetic resonance (NMR) experiments, are averages over broad ensembles
      of conformations. We aim to develop a database for the analysis of such data in
      terms of conformational distributions of the protein backbone rather than of
      individual high-resolution structures. Results: Glutton is the largest available
      database linking chemical shifts and protein 3D structures (5,270 entries
      organized in three levels) and is searchable via a python script. It generates
      statistical distributions of phi - psi dihedral angles based on chemical shifts
      or vice versa. Such phi - psi distributions are used to calculate structural
      ensembles of partially disordered proteins from their chemical shifts. For folded
      proteins, such ensembles are excellent starting points for further refinement
      with additional experimental restraints (structure determination), or
      computational methods (structure prediction). Availability: Glutton is freely
      available at https://github.com/YeeHo/Glutton. Supplementary Information:
      Supplementary data are available at Bioinformatics online.

PMID- 30184056
TI  - First percutaneous COMBO therapy of tricuspid regurgitation using direct
      annuloplasty and staged edge-to-edge repair in a surgical-like Clover technique.

PMID- 30184057
TI  - Co-registration and analysis of multiple imaging mass spectrometry datasets
      targeting different analytes.
AB  - Motivation: MALDI imaging mass spectrometry (IMS) has been successfully used to
      image a variety of biomolecules. Imaging of the many classes of biomolecules is
      often achieved through several incompatible sample preparations. Thus, multiple
      datasets must be acquired from multiple tissue sections to obtain a total
      molecular overview of a single sample. Addressing the need for single datasets
      from multiple IMS analyses, we developed the R package RegCombIMS as an extension
      of R package Cardinal to co-register, combine and create single IMS datasets
      acquired from serial sections of tissue. Results: Dataset recombination and
      analysis is achieved by registration of the IMS datasets to a single coordinate
      space. The workflow allows for correlation of ions from IMS acquisitions that
      require incompatible sample preparations as well as multivariate analysis to mine
      the combined dataset for rapid and more thorough molecular query. Availability:
      The source code and example data are freely available at
      https://github.com/NHPatterson/RegCombIMS. All code was implemented in R.
      Supplementary information: Supplementary data are available at Bioinformatics
      online.

PMID- 30184058
TI  - Bayesian integrative model for multi-omics data with missingness.
AB  - Motivation: Integrative analysis of multi-omics data from different high
      throughput experimental platforms provides valuable insight into regulatory
      mechanisms associated with complex diseases, and gains statistical power to
      detect markers that are otherwise overlooked by single-platform omics analysis.
      In practice, a significant portion of samples may not be measured completely due
      to insufficient tissues or restricted budget (e.g. gene expression profile are
      measured but not methylation). Current multi-omics integrative methods require
      complete data. A common practice is to ignore samples with any missing platform
      and perform complete case analysis, which leads to substantial loss of
      statistical power. Methods: In this article, inspired by the popular Integrative
      Bayesian Analysis of Genomics data (iBAG), we propose a full Bayesian model that
      allows incorporation of samples with missing omics data. Results: Simulation
      results show improvement of the new full Bayesian approach in terms of outcome
      prediction accuracy and feature selection performance when sample size is limited
      and proportion of missingness is large. When sample size is large or the
      proportion of missingness is low, incorporating samples with missingness may
      introduce extra inference uncertainty and generate worse prediction and feature
      selection performance. To determine whether and how to incorporate samples with
      missingness, we propose a self-learning cross-validation (CV) decision scheme.
      Simulations and a real application on child asthma dataset demonstrate superior
      performance of the CV decision scheme when various types of missing mechanisms
      are evaluated. Availability and implementation: Freely available on the GitHub at
      https://github.com/CHPGenetics/FBM. Supplementary information: Supplementary data
      are available at Bioinformatics online.

PMID- 30184059
TI  - Rapid onset of severe septic shock in the pregnant mouse.
AB  - Aims: Globally, sepsis is a major cause of mortality through the combination of
      cardiovascular collapse and multi-organ dysfunction. Pregnancy appears to
      increase the risk of death in sepsis, but the exact reason for the greater
      severity is unclear. In this study, we used polymicrobial sepsis induced by
      caecal ligation and puncture (CLP) and high-dose intraperitoneal
      lipopolysaccharide (LPS; 10 or 40mg, serotype 0111: B4) to test the hypotheses
      that pregnant mice are more susceptible to sepsis and that this susceptibility
      was mediated through an excessive innate response causing a more severe
      cardiovascular collapse rather than a reduction in microbe killing. Methods and
      Results: Initial studies found that mortality rates were greater, and that death
      occurred sooner in pregnant mice exposed to CLP and LPS. In pregnant and non
      pregnant CD1 mice monitored with radiotelemetry probes, cardiovascular collapse
      occurred sooner in pregnant mice, but once initiated, occurred over a similar
      timescale. In a separate study, tissue, serum and peritoneal fluid (for protein,
      flow cytometry, nitric oxide and bacterial load studies) were collected. At
      baseline, there was no apparent Th1/Th2 bias in pregnant mice. Post CLP, the
      circulating cytokine response was the same, but leukocyte infiltration in the
      lung was greater in pregnant mice, but only TNFalpha levels were greater in lung
      tissue. The bacterial load in blood and peritoneal fluid was similar in both
      groups. Conclusion: Sepsis-related mortality was markedly greater in pregnant
      mice. Cardiovascular collapse and organ dysfunction occurred sooner in pregnancy,
      but bacterial killing was similar. Circulating and tissue cytokine levels were
      similar, but immune cell extravasation into other organs was greater in pregnant
      mice. These data suggest that an excessive innate immune system response, as
      shown by the exaggerated lung infiltration of leukocytes may be responsible for
      the greater mortality. Approaches that reduce off-site trafficking may improve
      the prognosis of sepsis in pregnancy.

PMID- 30184060
TI  - Patent foramen ovale with an enormous right-to-left shunt: unusual reversible
      cause of hypoxia in carcinoid syndrome.

PMID- 30184061
TI  - Microembolic signals produced by a steam pop during human mitral isthmus linear
      ablation.

PMID- 30184062
TI  - De novo construction of polyploid linkage maps using discrete graphical models.
AB  - Motivation: Linkage maps are used to identify the location of genes responsible
      for traits and diseases. New sequencing techniques have created opportunities to
      substantially increase the density of genetic markers. Such revolutionary
      advances in technology have given rise to new challenges, such as creating high
      density linkage maps. Current multiple testing approaches based on pairwise
      recombination fractions are underpowered in the high-dimensional setting and do
      not extend easily to polyploid species. To remedy these issues, we propose to
      construct linkage maps using graphical models either via a sparse Gaussian copula
      or a nonparanormal skeptic approach. Results: We determine linkage groups,
      typically chromosomes, and the order of markers in each linkage group by
      inferring the conditional independence relationships among large numbers of
      markers in the genome. Through simulations, we illustrate the utility of our map
      construction method and compare its performance with other available methods,
      both when the data are clean and contain no missing observations and when data
      contain genotyping errors. Our comprehensive map construction method makes full
      use of the dosage SNP data to reconstruct linkage map for any bi-parental diploid
      and polyploid species. We apply the proposed method to three genotype datasets:
      barley, peanut, and potato from diploid and polyploid populations. Availability:
      The method is implemented in the R package netgwas which is freely available at
      https://cran.r-project.org/web/packages/netgwas. Supplementary information:
      Supplementary data are available at Bioinformatics online.

PMID- 30184063
TI  - The importance of health behaviours and especially broader self-management
      abilities for older Turkish immigrants.
AB  - Background: This study aims to identify the relationships between health
      behaviours, self-management abilities, physical health, depressive symptoms and
      well-being among Turkish older immigrants. Methods: A total of 2350 older Turkish
      migrants aged > 65 years residing in Rotterdam, the Netherlands were identified
      using the municipal register of which 680 respondents completed the
      questionnaires (response rate of 32%). Results: Average age of the respondents
      was 72.90 (standard deviation 5.02) (range 66-95) years and about half of them
      were women (47.6%). The majority of respondents reported having a low education
      (80.3%), low income level (83.4%), is chronically ill (90.6%), overweight (86.5%)
      and about half obese (46.0%). More than half of the respondents eat enough fruit
      (58.2%) and vegetables per week (55.3%). About a third of the respondents smoke
      (33.5%) and 43.0% can be considered to be physically active. Looking at the
      health behaviours a weak positive relationship was found between eating enough
      vegetables and well-being (beta = 0.14; P = 0.017). In addition, weak
      relationships were found between physical activity and depressive symptoms (beta
      = -0.16; P = 0.007), smoking and depressive symptoms (beta = 0.16; P = 0.009) and
      self-management abilities and physical health (beta = 0.17; P = 0.015). Strongest
      relationships were found between self-management abilities and depressive
      symptoms (beta = -0.39; P < 0.001) and self-management abilities with overall
      well-being (beta = 0.49; P < 0.001). Conclusions: From this study, we can
      conclude that next to health behaviours broader self-management abilities to
      maintain overall well-being are important for Turkish older people. Interventions
      to improve self-management abilities may help Turkish older people better deal
      with function losses and chronic diseases as they age further.

PMID- 30184064
TI  - Systemic complications of acromegaly and the impact of the current treatment
      landscape: an update.
AB  - Acromegaly is a chronic systemic disease with many complications and is
      associated with increased mortality when not adequately treated. Significant
      advances in acromegaly treatment, as well as in the treatment of many of its
      complications, mainly diabetes mellitus, heart failure and arterial hypertension,
      were achieved in the last decades. These developments allowed change in both
      prevalence and severity of some acromegaly complications and furthermore resulted
      in a reduction of mortality. Nowadays, mortality seems to be similar to the
      general population in adequately treated patients with acromegaly. In this
      review, we will update the knowledge in complications of acromegaly and detail
      the effects of different acromegaly treatment options on these complications.
      Incidence of mortality, its correlation with growth hormone (cumulative exposure
      vs last value) and insulin-like growth factor type I levels and the shift in the
      main cause of mortality in patients with acromegaly will be also addressed.

PMID- 30184065
TI  - Predicting Evolution of the Transcription Regulatory Network in a Bacteriophage.
AB  - Prediction of evolutionary trajectories has been an elusive goal, requiring a
      deep knowledge of underlying mechanisms that relate genotype to phenotype plus
      understanding how phenotype impacts organismal fitness. We tested our ability to
      predict molecular regulatory evolution in a bacteriophage (T7) whose RNA
      polymerase (RNAP) was altered to recognize a heterologous promoter differing by
      three nucleotides from the wild-type promoter. A mutant of wild-type T7 lacking
      its RNAP gene was passaged on a bacterial strain providing the novel RNAP in
      trans. Higher fitness rapidly evolved. Predicting the evolutionary trajectory of
      this adaptation used measured in vitro transcription rates of the novel RNAP on
      the six promoter sequences capturing all possible one-step pathways between the
      wild-type and the heterologous promoter sequences. The predictions captured some
      of the regulatory evolution but failed both in explaining 1) a set of T7
      promoters that consistently failed to evolve and 2) some promoter evolution that
      fell outside the expected one-step pathways. Had a more comprehensive set of
      transcription assays been undertaken initially, all promoter evolution would have
      fallen within predicted bounds, but the lack of evolution in some promoters is
      unresolved. Overall, this study points toward the increasing feasibility of
      predicting evolution in well-characterized, simple systems.

PMID- 30184066
TI  - A Novel Passive Sampling Technique for Collecting Adult Necrophilous Insects
      Arriving at Neonate Pig Carcasses.
AB  - Neonate pigs have been used as decomposition models in experimental forensic
      entomology studies. Their small size, however, poses challenges to traditional
      sampling methods of necrophilous insects, like the sweep net, the most commonly
      used sampling method in forensic entomology research and practice. Previous
      research experimentally demonstrated the potential for sticky traps as an
      effective sampling method for collecting necrophilous insects from neonate pigs.
      While sticky traps effectively sampled fly diversity from the pigs, they shared
      with the sweep net low sample diversity and abundance, particularly of
      necrophilous beetles. Motivated by chemosensory host-finding of necrophilous
      insects and the architecture of carrion-mimicking thermogenic flowers, we
      developed a 'vented-chamber' method and optimized its design experimentally. In
      this approach, a neonate pig was transiently enclosed in a chamber. The
      decomposition process thermally convected the natural decomposition odors in the
      headspace above the pig toward a pair of sticky traps. The vented-chamber method
      collected significantly more necrophilous flies, representing a greater
      diversity, than the sweep net. Nevertheless, this approach caught few beetles,
      and hand collections must be used as well to most effectively sample beetle
      diversity.

PMID- 30184069
TI  - Phylogenetic approaches to identifying fragments of the same gene, with
      application to the wheat genome.
AB  - Motivation: As the time and cost of sequencing decrease, the number of available
      genomes and transcriptomes rapidly increases. Yet the quality of the assemblies
      and the gene annotations varies considerably and often remains poor, affecting
      downstream analyses. This is particularly true when fragments of the same gene
      are annotated as distinct genes, which may cause them to be mistaken as paralogs.
      Results: In this study, we introduce two novel phylogenetic tests to infer non
      overlapping or partially overlapping genes that are in fact parts of the same
      gene. One approach collapses branches with low bootstrap support and the other
      computes a likelihood ratio test. We extensively validated these methods by 1)
      introducing and recovering fragmentation on the bread wheat, Triticum aestivum
      cv. Chinese Spring, chromosome 3B; 2) by applying the methods to the low-quality
      3B assembly and validating predictions against the high-quality 3B assembly; and
      3) by comparing the performance of the proposed methods to the performance of
      existing methods, namely Ensembl Compara and ESPRIT. Application of this
      combination to a draft shotgun assembly of the entire bread wheat genome revealed
      1221 pairs of genes that are highly likely to be fragments of the same gene. Our
      approach demonstrates the power of fine-grained evolutionary inferences across
      multiple species to improving genome assemblies and annotations. Availability: An
      open source software tool is available at https://github.com/DessimozLab/esprit2.
      Supplementary information: Supplementary data are available at Bioinformatics
      online.

PMID- 30184067
TI  - Analysis of Genome-Wide Differentiation between Native and Introduced Populations
      of the Cupped Oysters Crassostrea gigas and Crassostrea angulata.
AB  - The Pacific cupped oyster is genetically subdivided into two sister taxa,
      Crassostrea gigas and Crassostrea angulata, which are in contact in the north
      western Pacific. The nature and origin of their genetic and taxonomic
      differentiation remains controversial due the lack of known reproductive barriers
      and the high degree of morphologic similarity. In particular, whether the
      presence of ecological and/or intrinsic isolating mechanisms contributes to
      species divergence is unknown. The recent co-introduction of both taxa into
      Europe offers a unique opportunity to test how genetic differentiation is
      maintained under new environmental and demographic conditions. We generated a
      pseudochromosome assembly of the Pacific oyster genome using a combination of BAC
      end sequencing and scaffold anchoring to a new high-density linkage map. We
      characterized genome-wide differentiation between C. angulata and C. gigas in
      both their native and introduced ranges, and showed that gene flow between
      species has been facilitated by their recent co-introductions in Europe.
      Nevertheless, patterns of genomic divergence between species remain highly
      similar in Asia and Europe, suggesting that the environmental transition caused
      by the co-introduction of the two species did not affect the genomic architecture
      of their partial reproductive isolation. Increased genetic differentiation was
      preferentially found in regions of low recombination. Using historical
      demographic inference, we show that the heterogeneity of differentiation across
      the genome is well explained by a scenario whereby recent gene flow has eroded
      past differentiation at different rates across the genome after a period of
      geographical isolation. Our results thus support the view that low-recombining
      regions help in maintaining intrinsic genetic differences between the two
      species.

PMID- 30184071
TI  - Efficacy of designer K11 antimicrobial peptide (a hybrid of melittin, cecropin A1
      and magainin 2) against Acinetobacter baumannii-infected wounds.
AB  - Due to emergence of multidrug resistance in pathogens, the attention of the
      scientific community is now directed towards strengthening the reservoir of
      antimicrobial compounds. Prior to in vivo studies, the interaction and
      penetration of a hybrid peptide K11 in bacterial cells using confocal microscopy
      was assessed which was observed as early as 10 min after incubation with the
      peptide. Cell lysis along with leakage of cytoplasmic content was confirmed by
      electron microscopy. To evaluate the in vivo performance of the peptide, it was
      contained in carbopol hydrogel. Efficacy of the hydrogel formulation was then
      evaluated against Acinetobacter baumannii-infected wounds using a murine excision
      model. Treatment resulted in restoration of body weight, complete clearance of
      infection from the wound by day 7 and 99% wound enclosure by day 21, in contrast
      to the persistence of infection and 70% wound enclosure in the infected group.
      Further, this treatment resulted in a 2.6-fold decrease in the levels of
      malondialdehyde along with a 4.5-fold increase in the levels of catalase on day
      3. Appearance of normal histo-architecture was observed in the treatment group.
      Based on these results, the peptide hydrogel can be exploited in future as one of
      the strategies for developing a topical anti-infective therapeutic agent.

PMID- 30184068
TI  - Pan-Parastagonospora Comparative Genome Analysis-Effector Prediction and Genome
      Evolution.
AB  - We report a fungal pan-genome study involving Parastagonospora spp., including 21
      isolates of the wheat (Triticum aestivum) pathogen Parastagonospora nodorum, 10
      of the grass-infecting Parastagonospora avenae, and 2 of a closely related
      undefined sister species. We observed substantial variation in the distribution
      of polymorphisms across the pan-genome, including repeat-induced point mutations,
      diversifying selection and gene gains and losses. We also discovered chromosome
      scale inter and intraspecific presence/absence variation of some sequences,
      suggesting the occurrence of one or more accessory chromosomes or regions that
      may play a role in host-pathogen interactions. The presence of known
      pathogenicity effector loci SnToxA, SnTox1, and SnTox3 varied substantially among
      isolates. Three P. nodorum isolates lacked functional versions for all three
      loci, whereas three P. avenae isolates carried one or both of the SnTox1 and
      SnTox3 genes, indicating previously unrecognized potential for discovering
      additional effectors in the P. nodorum-wheat pathosystem. We utilized the pan
      genomic comparative analysis to improve the prediction of pathogenicity effector
      candidates, recovering the three confirmed effectors among our top-ranked
      candidates. We propose applying this pan-genomic approach to identify the
      effector repertoire involved in other host-microbe interactions involving
      necrotrophic pathogens in the Pezizomycotina.

PMID- 30184070
TI  - The European Registry for Patients with Mechanical Circulatory Support
      (EUROMACS): first EUROMACS Paediatric (Paedi-EUROMACS) report.
AB  - OBJECTIVES: EUROMACS is a registry of the European Association for Cardio
      Thoracic Surgery (EACTS) whose purpose is to gather clinical data related to
      durable mechanical circulatory support for scientific purposes and to publish
      annual reports. Because the treatment of children with end-stage heart failure
      has several significantly different characteristics than the treatment of adults,
      data and outcomes of interventions are analysed in this dedicated paediatric
      report. METHODS: Participating hospitals contributed pre-, peri- and long-term
      postoperative data on mechanical circulatory support implants to the registry.
      Data for all implants in paediatric patients (<=19 years of age) performed from 1
      January 2000 to 31 December 2017 were analysed. This report includes updates of
      patient characteristics, implant frequency, outcome (including mortality rates,
      transplants and recovery rates) as well as adverse events. RESULTS: Twenty-five
      hospitals contributed 237 registered implants in 210 patients (81 ?, 129 ?) to
      the registry. The most frequent diagnosis was any form of cardiomyopathy (71.4%)
      followed by congenital heart disease (18.6%). Overall mean support time on a
      device was 11.6 months (+/-16.5 standard deviation). A total of 173 children
      (82.4%) survived to transplant, recovery or are ongoing; 37 patients (17.6%) died
      while on support within the observed follow-up time. At 12 months 38% of patients
      received transplants, 7% were weaned from their device and 15% died. At 24
      months, 51% of patients received transplants, 17% died while on support, 22% were
      on a device and 9% were explanted due to myocardial recovery. The adverse events
      rate per 100 patient-months was 0.2 for device malfunction, 0.05 for major
      bleeding, 0.06 for major infection and 0.03 for neurological events within the
      first 3 months after implantation. CONCLUSIONS: The first paediatric EUROMACS
      report reveals a low transplant rate in European countries within the first 2
      years of implantation compared to US data. The 1-year survival rate seems to be
      satisfactory. Device malfunction including pump chamber changes due to thrombosis
      was the most frequent adverse event.

PMID- 30184072
TI  - Roles of Figla/figla in Juvenile Ovary Development and Follicle Formation During
      Zebrafish Gonadogenesis.
AB  - Sex determination and differentiation are complex processes. As a juvenile
      hermaphrodite or undifferentiated gonochorist, zebrafish undergo a special
      juvenile ovarian phase during sex differentiation, making it an excellent model
      for studying early oogenesis and folliculogenesis. We provide lines of evidence
      at morphological, molecular, and genetic levels for roles of factor in the
      germline alpha (Figla), an oocyte-specific transcription factor, in early
      zebrafish gonadogenesis. As in mammals, Figla/figla was also expressed in the
      gonads and its expression in the ovary was also restricted to early oocytes.
      Disruption of figla gene by CRISPR/Cas9 led to an all-male phenotype in the
      mutant. Detailed analysis of early gonadal development showed that the germ cells
      in the mutant were clustered in cysts and underwent meiosis, forming oocytes at
      prefollicular chromatin nucleolar (CN) stage (stage IA). However, the subsequent
      transition from cystic CN oocytes to individual follicular perinucleolar oocytes
      (stage IB) was blocked, resulting in an all-male phenotype in the mutant. The
      phenotype of figla mutant could not be rescued by estrogen treatment, in contrast
      to cyp19a1a mutant, and introduction of tp53 mutation also had no effect, unlike
      in fancd1 and fancl mutants. Transcriptome analysis revealed that many biological
      processes and pathways related to germ cell development, especially oogenesis,
      were upregulated in the presence of Figla and that the regulation of figla
      expression may involve heat shock proteins. Our results strongly suggest
      important roles for Figla in juvenile ovary development, especially the formation
      of individual follicles from cystic oocytes.

PMID- 30184073
TI  - Physical activity and exercise in adults with type 1 diabetes: understanding
      their needs using a person-centered approach.
AB  - Physical activity is a key component in the management of diabetes, but most
      people do not engage in recommended levels of physical activity. A recent
      consensus statement on exercise management in type 1 diabetes (T1D) fails to
      mention behavioral change and the specific determinants impacting on exercise
      management. The aim of this study is to investigate the needs of adults with T1D
      around physical activity and the challenges they face. Using a person-centered
      approach, focus groups and individual semi-structured interviews recorded the
      perspectives of 67 adults aged >=18 with diabetes. Four global themes were
      identified: (i) it's a balancing act, (ii) winging it, (iii) engagement and (iv)
      encouraging uptake. These findings suggest that adults with T1D find it difficult
      to manage their diabetes and physical activity and decision-making is based on
      trial and error with minimal input from healthcare professionals. Participants
      want more information to enable them to manage their diabetes and physical
      activity effectively. Adults with T1D face unique challenges in relation to
      physical activity. Participants reported key determinants for being active.
      Research is needed to understand how physical activity promotion is best
      developed for those with T1D and the preparedness of healthcare professionals for
      delivering guidance to adults with T1D.

PMID- 30184075
TI  - Influence of medical shortage on GP burnout: a cross-sectional study.
AB  - Background: Burnout is a common occurrence among GPs, decreasing quality of and
      access to care and impacting both physician and patient health. The link between
      burnout and low medical density has never been studied. Objectives: This study
      aimed to assess the prevalence of burnout and its related factors, including low
      medical density, among GPs. Method: We conducted a cross-sectional survey. A self
      administered questionnaire was sent to all of the 1632 GPs in Normandy, France,
      in September 2015. The Maslach Burnout Inventory was used to assess the three
      burnout dimensions: emotional exhaustion (EE), depersonalization (DP) and low
      personal accomplishment (PA). Results: In all, 501 GPs sent back their
      questionnaire (response rate: 30.7%); 487 questionnaires were analysed. Burnout
      had been experienced by 43.3% of the physicians in the sample. Nearly 24% of the
      respondents scored high EE, 27.3% scored high DP, and 13.3% scored low PA. Low
      medical density [odds ratios (OR): 2.16 (1.31-3.54)], and intent to quit [OR:
      4.40 (2.59-7.47)] were strongly linked to the three burnout dimensions. Burnout
      was not linked with quantitative workload. Conclusion: Burnout among GPs was
      common. Low medical density and intent to quit were strong predictors of burnout.
      Given the current medical demographic crisis, these results highlight the
      relationship between burnout and medical shortage. Qualitative workload may have
      a more significant influence on burnout than quantitative workload. Recruiting
      more GPs is necessary, but may prove insufficient in fighting burnout. Preventive
      and curative actions are required, especially in areas with low medical density.

PMID- 30184074
TI  - Pairs of Adjacent Conserved Noncoding Elements Separated by Conserved Genomic
      Distances Act as Cis-Regulatory Units.
AB  - Comparative genomic studies have identified thousands of conserved noncoding
      elements (CNEs) in the mammalian genome, many of which have been reported to
      exert cis-regulatory activity. We analyzed ~5,500 pairs of adjacent CNEs in the
      human genome and found that despite divergence at the nucleotide sequence level,
      the inter-CNE distances of the pairs are under strong evolutionary constraint,
      with inter-CNE sequences featuring significantly lower transposon densities than
      expected. Further, we show that different degrees of conservation of the inter
      CNE distance are associated with distinct cis-regulatory functions at the CNEs.
      Specifically, the CNEs in pairs with conserved and mildly contracted inter-CNE
      sequences are the most likely to represent active or poised enhancers. In
      contrast, CNEs in pairs with extremely contracted or expanded inter-CNE sequences
      are associated with no cis-regulatory activity. Furthermore, we observed that
      functional CNEs in a pair have very similar epigenetic profiles, hinting at a
      functional relationship between them. Taken together, our results support the
      existence of epistatic interactions between adjacent CNEs that are distance
      sensitive and disrupted by transposon insertions and deletions, and contribute to
      our understanding of the selective forces acting on cis-regulatory elements,
      which are crucial for elucidating the molecular mechanisms underlying adaptive
      evolution and human genetic diseases.

PMID- 30184076
TI  - Child maltreatment prevention: a content analysis of European national policies.
AB  - Background: Child maltreatment is a major public health concern, which worsens
      inequalities and perpetuates social injustice through its far-reaching impacts on
      the health and development of children affected. The aim of this article was to
      provide a content analysis of the national policies presently used to address
      child maltreatment and provide an overview of prevention practices being employed
      in countries of the World Health Organization (WHO) European Region. This
      analysis will aid in identifying, which policy areas still require further work
      to prevent child maltreatment. Methods: Three search methods were employed to
      identify national policies on child maltreatment. A framework based on WHO
      guidelines for the development of policies was used to conduct a policy analysis
      of the identified national policies. Results: Two hundred and seventy-eight
      national policies were identified; of these, 68 met the inclusion criteria for
      further analysis representing 75% of the WHO Europe Region Member States. Whereas
      the majority of policies fulfilled most of the WHO criteria for effective policy
      making, only 34% had a budget and 6% had quantified objectives. Plans to
      implement proven child maltreatment prevention interventions were high, with the
      exception of some countries where the health sector is in the lead. Conclusions:
      The key policy areas requiring improvement were quantifiable objectives and
      allocated defined budgets. Hospital-based and home-based child maltreatment
      interventions were also not widely planned for implementation. Encouraging
      progress is being made on national policy development to prevent child
      maltreatment. There are as of yet, several key areas, which warrant increased
      attention in future policy-making.

PMID- 30184077
TI  - Canola meal produced from high-protein or conventional varieties of canola seeds
      may substitute soybean meal in diets for gestating and lactating sows without
      compromising sow or litter productivity.
AB  - An experiment was conducted to test the hypothesis that productivity of sows fed
      diets containing canola meal produced from high-protein or conventional varieties
      of canola seeds is not different from that of sows fed corn-soybean meal (SBM)
      diets. A total of 180 sows (initial BW: 207.8 +/- 29.11 kg) were randomly
      allotted to 1 of 5 diets with 36 to 40 sows per diet. A 2-phase feeding program
      was used with gestation diets fed from day 7 of gestation to farrowing and
      lactation diets fed during the lactation period and from weaning to first estrus.
      The 5 diets within each phase consisted of a control diet based on corn and SBM,
      2 diets were based on corn and high-protein canola meal (CM-HP) that was included
      to replace 50 or 100% of the SBM in the control diet, and 2 diets contained
      conventional canola meal (CM-CV) included to replace 50 or 100% of the SBM in the
      control diet. Soybean hulls were included in diets fed during gestation to
      standardize the concentration of NDF to approximately 13% in all diets. However,
      no soybean hulls were used in lactation diets resulting in increased
      concentrations of NDF as the dietary concentration of CM-HP or CM-CV increased.
      Results of the experiment indicated that there were no differences in sow BW
      changes during gestation, in sow BW on day 1 post-farrowing, or at weaning due to
      dietary treatments. No differences were observed among diets in ADFI during
      gestation or lactation or in the number of total pigs born, pigs born alive,
      still-born pigs, or weaned pigs per litter. Likewise, no differences were
      observed among diets in litter birth weight, live litter birth weight, litter BW
      at weaning, or litter ADG. As the inclusion level of CM-HP or CM-CV increased,
      the percentage of pigs surviving during the lactation period increased (linear, P
      < 0.05), but the wean to first estrus interval also increased as the dietary
      concentration of CM-CV increased (linear, P < 0.05). Average pig BW at weaning
      and pig ADG decreased (linear, P < 0.05) as the inclusion level of CM-HP
      increased. No differences were observed between CM-HP and CM-CV with the
      exception that pigs born from sows fed CM-CV during gestation had greater (P <
      0.05) average live pig birth weight compared with pigs born from sows fed CM-HP
      during gestation. Results of this experiment indicate that CM-HP or CM-CV may
      replace all SBM in diets fed to sows during gestation and lactation.

PMID- 30184078
TI  - Saccharomyces cerevisiae mitochondrial Por1/yVDAC1 (voltage-dependent anion
      channel 1) interacts physically with the MBOAT O-acyltransferase Gup1/HHATL in
      the control of cell wall integrity and programmed cell death.
AB  - Gup1 is the yeast counterpart of the high eukaryotes HHATL. This and the close
      homologue Gup2/HHAT regulate the Hedgehog morphogenic, developmental pathway. In
      yeasts, a similar paracrine pathway is not known though the Deltagup1 mutant is
      associated with morphology and proliferation/death processes. As a first step
      toward identifying the actual molecular/enzymatic function of Gup1, this work
      identified by co-immunoprecipitation the yeast mitochondria membrane VDAC1/Por1
      as a physical partner of Gup1. Gup1 locates in the ER and the plasma membrane. It
      was now confirmed to further locate, as Por1, in the mitochondrial sub-cellular
      fraction. The yeast Por1-Gup1 association was found important for (i) the
      sensitivity to cell wall perturbing agents and high temperature, (ii) the
      differentiation into structured colonies, (iii) the size achieved by
      multicellular aggregates/mats and (iv) acetic-acid-induced Programmed Cell Death.
      Moreover, the absence of Gup1 increased the levels of POR1 mRNA, while decreasing
      the amounts of intracellular Por1, which was concomitantly previously known to be
      secreted by the mutant but not by wt. Additionally, Por1 patchy distribution in
      the mitochondrial membrane was evened. Results suggest that Por1 and Gup1
      collaborate in the control of colony morphology and mat development, but more
      importantly of cellular integrity and death.

PMID- 30184079
TI  - Impact of Single Gene and Pyramided Aphid-Resistant Soybean on Movement and
      Spatial Pattern of Soybean Aphid (Hemiptera: Aphididae).
AB  - Host plant resistance may be an effective option to manage soybean aphid, Aphis
      glycines (Matsumura) (Hemiptera: Aphididae), an important pest on soybean
      (Glycine max (L.) Merr.) in the U.S. Movement of soybean aphid may be altered by
      the presence of resistance (i.e., Rag [Resistance to Aphis glycines]) genes in
      soybean and changes in movement may affect the spatial pattern of a species. This
      study aims to assess the effects of Rag1 and pyramided Rag1+Rag2 aphid-resistant
      varieties on movement of soybean aphid under laboratory conditions and to
      evaluate potential impacts of this movement on spatial pattern of soybean aphid
      under field conditions. Results from the greenhouse study showed more movement of
      soybean aphid on both aphid-resistant varieties than the susceptible variety when
      aphids were placed on unifoliate leaves and no statistically significant
      difference in movement between Rag1 and pyramided Rag1+Rag2 varieties. When
      aphids were placed on new growth, movement was greater on pyramided Rag1+Rag2
      than the Rag1 and susceptible variety. However, under field conditions, the
      spatial patterns of soybean aphid in plots with susceptible, Rag1 or pyramided
      Rag1+Rag2 varieties were aggregated and did not differ among varieties in
      vegetative and reproductive growth stages. These results are of relevance because
      they suggest that aspects of soybean aphid management that may be sensitive to
      changes in spatial pattern of the pest (e.g., natural enemy efficacy and sampling
      plans) may not be impacted by implementation of varieties with these resistance
      genes for host plant resistance.

PMID- 30184080
TI  - Resting Heart Rate "Kinetics": Paradox or Means to Understand the Link Between
      Hypertension and Heart Failure?

PMID- 30184081
TI  - A novel p.(Glu111Val) missense mutation in GUCA1A associated with cone-rod
      dystrophy leads to impaired calcium sensing and perturbed second messenger
      homeostasis in photoreceptors.
AB  - Guanylate Cyclase-Activating Protein 1 (GCAP1) regulates the enzymatic activity
      of the photoreceptor guanylate cyclases (GC), leading to inhibition or activation
      of the cyclic guanosine monophosphate (cGMP) synthesis depending on its Ca2+- or
      Mg2+-loaded state. By genetically screening a family of patients diagnosed with
      cone-rod dystrophy, we identified a novel missense mutation with autosomal
      dominant inheritance pattern (c.332A>T; p.(Glu111Val); E111V from now on) in the
      GUCA1A gene coding for GCAP1. We performed a thorough biochemical and biophysical
      investigation of wild type (WT) and E111V human GCAP1 by heterologous expression
      and purification of the recombinant proteins. The E111V substitution disrupts the
      coordination of the Ca2+ ion in the high-affinity site (EF-hand 3, EF3), thus
      significantly decreasing the ability of GCAP1 to sense Ca2+ (~80-fold higher
      Kdapp compared to WT). Both WT and E111V GCAP1 form dimers independently on the
      presence of cations, but the E111V Mg2+-bound form is prone to severe aggregation
      over time. Molecular dynamics simulations suggest a significantly increased
      flexibility of both the EF3 and EF4 cation binding loops for the Ca2+-bound form
      of E111V GCAP1, in line with the decreased affinity for Ca2+. In contrast, a more
      rigid backbone conformation is observed in the Mg2+-bound state compared to the
      WT, which results in higher thermal stability. Functional assays confirm that
      E111V GCAP1 interacts with the target GC with a similar apparent affinity (EC50);
      however, the mutant shifts the GC inhibition out of the physiological [Ca2+]
      (IC50E111V ~10 MUM), thereby leading to the aberrant constitutive synthesis of
      cGMP under conditions of dark-adapted photoreceptors.

PMID- 30184082
TI  - Goal Adjustment and Well-Being: The Role of Optimism in Patients with Chronic
      Pain.
AB  - Background: Chronic pain directly or indirectly interferes with valued personal
      goals. Goal adjustment plays a central role in patients' adaptation. Studies on
      the relationship between optimism and goal regulation have shown that people with
      high dispositional optimism adjust their goals in a flexible way, and that
      flexible goal adjustment promotes quality of life. Purpose: The aim of this study
      was to analyze the relationship among optimism, goal adjustment, and adaptation
      in patients with chronic pain. Methods: A sample of 258 patients with chronic
      musculoskeletal pain completed questionnaires on optimism, reengagement,
      disengagement, flexibility, tenacity, rumination, purpose in life, well-being,
      pain intensity, daily functioning, and impairment. Results: Structural equation
      modeling analysis showed that optimism had a positive association with
      reengagement, flexibility, and tenacity, and a negative association with
      disengagement. Disengagement was positively associated with rumination, whereas
      reengagement, flexibility, and tenacity were associated with higher levels of
      purpose in life, which were strongly associated with adaptation in patients with
      chronic pain. Conclusions: This study supports the conclusions of previous
      research on the role of goal adjustment as a mediator variable between optimism
      and well-being.

PMID- 30184084
TI  - A Critical Review of Botulinum Toxin Type A in the Prophylactic Treatment of
      Chronic Migraine in Adults.
AB  - Background: Migraine is a severe disabling condition, ranked by World Health
      Organization as the 6th highest cause of disability worldwide. It has great
      impact on the patient's quality of life, functionality, physical and mental
      health. The financial burden of migraine on the UK economy is conservatively
      estimated at L3.42 billion per year. Objectives: To perform an evidence-based
      literature review of the safety and efficacy of botulinum toxin type A (onaBoNTA)
      in the prophylactic treatment of adult patients suffering with chronic migraine
      (CM) in comparison to placebo. The best evidence identified, will be utilized to
      formulate a protocol for doctors managing CM in their aesthetic clinic. Methods:
      A comprehensive search of the current literature on the topic was performed by
      H.M. using Pubmed MEDLINE electronic database on the March 1, 2018. All articles
      up to and inclusive of this date were included. Articles were limited to human
      studies and those in the English language. In-vitro and animal studies were
      excluded. Results: A total of 260 articles were identified. Of these, the
      excellent-quality, high-strength (Level 1A) trials were short-listed to answer
      the research question. Conclusion: There is high quality level 1A evidence to
      support botulinum toxin type A treatment in adults with CM is well tolerated and
      considered safe. However, it is associated with increased risk of adverse events
      and there is still some uncertainty associated with the degree it improves
      outcome measures in comparison to placebo. This data has been used to formulate
      The London Aesthetic Migraine Protocol (LAMP), to provide safe evidence-based
      guidance for the appropriately trained and experienced aesthetic practitioner to
      manage CM in their aesthetic clinics.

PMID- 30184083
TI  - The Putative Smallest Introns in the Arabidopsis Genome.
AB  - Most eukaryotic genes contain introns, which are noncoding sequences that are
      removed during premRNA processing. Introns are usually preserved across
      evolutionary time. However, the sizes of introns vary greatly. In Arabidopsis,
      some introns are longer than 10 kilo base pairs (bp) and others are predicted to
      be shorter than 10 bp. To identify the shortest intron in the genome, we analyzed
      the predicted introns in annotated version 10 of the Arabidopsis thaliana genome
      and found 103 predicted introns that are 30 bp or shorter, which make up only
      0.08% of all introns in the genome. However, our own bioinformatics and
      experimental analyses found no evidence for the existence of these predicted
      introns. The predicted introns of 30-39 bp, 40-49 bp, and 50-59 bp in length are
      also rare and constitute only 0.07%, 0.2%, and 0.28% of all introns in the
      genome, respectively. An analysis of 30 predicted introns 31-59 bp long verified
      two in this range, both of which were 59 bp long. Thus, this study suggests that
      there is a limit to how small introns in A. thaliana can be, which is useful for
      the understanding of the evolution and processing of small introns in plants in
      general.

PMID- 30184085
TI  - Reliability of upper airway assessment using CBCT.
AB  - Background: Upper airway analysis is an often-cited use of CBCT imaging by
      orthodontists; however, the reliability of airway measurements using this
      technology is not fully established. Objective: To determine the intra-examiner
      and inter-examiner reliability of the complete process of volumetric and cross
      sectional area assessments of the upper airway using CBCT imaging. Materials and
      Methods: Six examiners of varying levels of education and clinical experience
      performed the steps necessary for airway analysis, including manual orientation,
      slice and threshold selection and measured nasopharyngeal, oropharyngeal,
      hypopharyngeal and total upper pharyngeal airway volumes in addition to minimum
      cross-sectional area on the CBCT images of 10 patients. All measurements were
      repeated after 4-weeks. Intra- and inter-examiner reliability was calculated
      using ICC and 95% CI. Results: Threshold selection showed poor intra- and poor
      inter-examiner reliability, whereas minimum cross-sectional area showed moderate
      intra- and poor inter-examiner reliability. Intra-examiner reliability of
      volumetric measurements varied based on the region assessed with ICC ranging from
      0.747 to 0.976, and was worst for hypopharynx and best for the oropharynx. Inter
      examiner reliability of volume measurements was generally lower, with ICC ranging
      from 0.175 to 0.945, and was worst for nasopharynx and best for the oropharynx.
      Conclusions: This study, for the first time, assessed the reliability of upper
      airway analysis with CBCT when all steps of image processing and measurement are
      performed by each examiner. Reliability improved with examiner experience, though
      was generally low for the hypopharynx and nasopharynx volumes and overall minimal
      cross-sectional area. The oropharyngeal volume was the only parameter to have
      excellent intra- and inter-examiner reliability.

PMID- 30184086
TI  - Quantitative and qualitative composition of yeast microbiota in spontaneously
      fermented grape musts obtained from cool climate grape varieties 'Rondo' and
      'Regent'.
AB  - The aim of the study was to characterise, quantitatively and qualitatively, the
      yeast microbiota found during spontaneous fermentation of grape musts obtained
      from the red grape varieties 'Rondo' and 'Regent'. For the research, grapes
      originating from two vineyards (Srebrna Gora and Spotkaniowka) located in
      southern Poland were used. Musts of the studied grape varieties provided a
      favourable environment for the growth of microorganisms. Musts obtained from
      fruits from the Spotkaniowka vineyard were characterised by a higher overall
      number of yeasts. A maximum number of cells were recorded from the fourth to the
      ninth day of the process, in all of the analysed musts. The growing season of
      2013 proved to be the least favourable for the growth of microorganisms on
      grapes, which resulted in their smaller number in the batches during spontaneous
      fermentation. During the process, succession of different groups of yeasts was
      observed. It was initiated by Hanseniaspora uvarum and Candida railenensis
      strains, which, with the progress of spontaneous fermentation, were replaced by
      Saccharomyces cerevisiae strains. Metschnikowia pulcherrima and Pichia
      membranifaciens yeasts were identified at both the beginning and the end of the
      process. During fermentation, Zygoascus meyerae, Kluyveromyces lactis and
      Nakazawaea ishiwadae strains were also identified.

PMID- 30184087
TI  - Editorial: Yeast cell aging and death.

PMID- 30184088
TI  - Cultural Transmission of Fine-Scale Fidelity to Feeding Sites May Shape Humpback
      Whale Genetic Diversity in Russian Pacific Waters.
AB  - Mitochondrial DNA (mtDNA) differences between humpback whales on different
      feeding grounds can reflect the cultural transmission of migration destinations
      over generations, and therefore represent one of the very few cases of gene
      culture coevolution identified in the animal kingdom. In Russian Pacific waters,
      photo-identification (photo-ID) studies have shown minimal interchange between
      whales feeding off the Commander Islands and those feeding in the Karaginsky
      Gulf, regions that are separated by only 500 km and have previously been lumped
      together as a single Russian feeding ground. Here, we assessed whether genetic
      differentiation exists between these 2 groups of humpback whales. We discovered a
      strong mtDNA differentiation between the 2 feeding sites (FST = 0.18, PhiST =
      0.14, P < 0.001). In contrast, nuclear DNA (nuDNA) polymorphisms, determined at 8
      microsatellite loci, did not reveal any differentiation. Comparing our mtDNA
      results with those from a previous ocean-basin study reinforced the differences
      between the 2 feeding sites. Humpback whales from the Commanders appeared most
      similar to those of the western Gulf of Alaska and the Aleutian feeding grounds,
      whereas Karaginsky differed from all other North Pacific feeding grounds.
      Comparison to breeding grounds suggests mixed origins for the 2 feeding sites;
      there are likely connections between Karaginsky and the Philippines and to a
      lesser extent to Okinawa, Japan, whereas the Commanders are linked to the Mexican
      breeding grounds. The mtDNA differentiation between the Commander Islands and
      Karaginsky Gulf suggests a case of gene-culture coevolution, correlated to
      fidelity to a specific feeding site within a particular feeding ground. From a
      conservation perspective, our findings emphasize the importance of considering
      these 2 feeding sites as separate management units.

PMID- 30184089
TI  - Insulin-like growth factor 1 receptor signaling regulates embryonic epicardial
      cell proliferation through focal adhesion kinase pathway.
AB  - Embryonic epicardial cells (EPCs) can facilitate cardiomyocyte growth through
      secreting several essential growth factors, and participate in cardiac
      development through auto-differentiating into many cardiac cell lineages. Proper
      proliferation of EPCs is the precondition of these functions, so it is quite
      necessary to explore the mechanisms involving in EPC proliferation. In this
      study, we aimed to explore whether insulin-like growth factor 1 receptor (IGF1R)
      signaling participated in regulating the proliferation of EPCs. Our results
      showed that the expressions of IGF1R and its ligands IGF1 and IGF2 can be clearly
      spotted on the epicardium layer from E11.5d to E17.5d. Inhibition of IGF1R
      signaling using picropodophyllin or NVP-AEW541 significantly decreased the
      proliferation activity and blocked the cell cycle progression of epicardial cells
      in vitro. On the contrary, activating IGF1R with recombinant IGF1 and IGF2
      promoted epicardial cell proliferation and cell cycle. We also found that
      decreased expression and phosphorylation of FAK in IGF1R inhibitor-treated cells
      and use of FAK inhibitor Y15 could significantly inhibit the IGFs-induced EPC
      proliferation. In conclusion, our results suggest that IGF1R signaling plays an
      important role in regulating EPC proliferation, and this effect may be mediated
      by FAK pathway.

PMID- 30184090
TI  - High Endemicity and Distinct Phylogenetic Characteristics of Sindbis Virus in
      Israel.
AB  - Sindbis virus (SINV) is a mosquito-borne Alphavirus responsible for outbreaks of
      SINV disease, mainly in north Europe. SINV has been isolated from mosquitoes in
      Israel since the 1980s but SINV disease outbreaks have never been recorded. To
      gain better understanding of the kinetics of SINV circulation in Israel, 3008
      mosquito pools, collected 2004-2006 and 2013-2015, were tested for SINV and
      phylogenetic analysis was conducted on partially sequenced SINV-positive pools.
      Results indicate possible expansion of SINV circulation across Israel in 2013
      2015 compared to 2004-2006 with 6.35% (191 pools) of total pools positive for
      SINV RNA. Phylogenetic analysis showed all sequenced Israeli SINV strains belong
      to genotype I and form, together with SINV sequences from Saudi Arabia, a
      distinct Middle Eastern cluster. With high endemicity of SINV and as a major
      crossroads for bird migration between Africa and Eurasia, Israel provides
      valuable information on SINV dynamics and pathogenicity.

PMID- 30184092
TI  - Therapeutic Monoclonal Antibodies and the Value of the Free Light Chain Assay in
      Myeloma.

PMID- 30184093
TI  - Effects of Pollen Feeding on Quality of Royal Jelly.
AB  - This study was carried out to assess the impact of pollen feeding from common
      floral sources in Thailand (e.g., tea, coffee, and bitter bush) on royal jelly
      (RJ) properties (i.e., protein pattern, (E)-9-hydroxydec-2-enoic acid (9-HDA),
      and (E)-10-hydroxy-2-decenoic acid (10-HDA) contents and antibacterial activity).
      The protein patterns from three different pollen were different, while RJ samples
      derived from bee colonies fed by different pollen, exhibited similar protein
      patterns. RJ samples from bee colonies fed by pollen from bitter bush and coffee
      possessed the higher 10-HDA levels than RJ collected from bee colonies fed by tea
      pollen. The 9-HDA was found in lower amount than 10-HDA in every sample. Even
      though the antibacterial activities of pollen were varied, however, RJ samples
      exhibited similar antibacterial properties. This is the first report showing that
      different pollen feeding affected 10-HDA contents, but not affected overall
      protein content and antibacterial properties.

PMID- 30184091
TI  - omega-6 Polyunsaturated Fatty Acids and Cardiometabolic Health: Current Evidence,
      Controversies, and Research Gaps.
AB  - The 2015 Dietary Guidelines for Americans recommend limiting the intake of
      saturated fatty acids (SFAs) to <10% of energy/d and replacing dietary SFAs with
      unsaturated fatty acids. A Presidential Advisory from the American Heart
      Association recently released its evaluation of the relation between dietary fats
      and cardiovascular disease (CVD), and also recommended a shift from SFAs to
      unsaturated fatty acids, especially polyunsaturated fatty acids (PUFAs), in
      conjunction with a healthy dietary pattern. However, the suggestion to increase
      the intake of PUFAs in general, and omega-6 (n-6) PUFAs in particular, continues
      to be controversial. This review was undertaken to provide an overview of the
      evidence and controversies regarding the effects of omega-6 PUFAs on
      cardiometabolic health, with emphasis on risks and risk factors for CVD (coronary
      heart disease and stroke) and type 2 diabetes mellitus (T2D). Results from
      observational studies show that higher intake of omega-6 PUFAs, when compared
      with SFAs or carbohydrate, is associated with lower risks for CVD events (10
      30%), CVD and total mortality (10-40%), and T2D (20-50%). Findings from
      intervention studies on cardiometabolic risk factors suggest that omega-6 PUFAs
      reduce concentrations of LDL cholesterol and non-HDL cholesterol in a dose
      dependent manner compared with dietary carbohydrate, and have a neutral effect on
      blood pressure. Despite the concern that omega-6 fatty acids increase
      inflammation, current evidence from studies in humans does not support this view.
      In conclusion, these findings support current recommendations to emphasize
      consumption of omega-6 PUFAs as a replacement of SFAs; additional randomized
      controlled trials with cardiometabolic disease outcomes will help to more clearly
      define the benefits and risks of this policy.

PMID- 30184094
TI  - Energy content and nutrient digestibility of diets containing Lactobacillus
      fermented barley or wheat fed to weaned pigs.
AB  - This study was conducted to determine the energy content and apparent total tract
      digestibility (ATTD) of nutrients of diets containing Lactobacillus-fermented
      barley or wheat fed to weaned pigs. Thirty-six weaned pigs (8.14 +/- 0.65 kg of
      body weight) were randomly assigned to 1 of 6 diets in a completely randomized
      design to give 6 replicates per diet. Pigs were individually housed in metabolism
      crates to determine digestible energy and metabolizable energy contents. Net
      energy was also calculated from the average of 2 equations published by Noblet et
      al. (1994). Diets were fed at 2.5 times the maintenance energy requirement for 10
      d of adaptation and 5 d of total but separate urine and fecal collection. Samples
      of barley or wheat were fermented for 90 d under anaerobic conditions with an
      inoculum of either homofermentative Lactobacillus plantarum (Homo) or
      heterofermentative L. buchneri (Hetero). Three diets were formulated based on
      either barley or wheat to consist of a control diet containing 42% unfermented
      grain and 2 diets containing either Homo-fermented or Hetero-fermented grain.
      Preplanned contrasts were used to evaluate the effects of the inclusion of
      fermented barley or wheat and to compare the effects of Homo-fermented with
      Hetero-fermented grains. Fermented wheat inclusion in a diet increased ATTD of
      gross energy and phosphorus, and retention of gross energy by 1.9%, 6.8%, and
      6.3%, respectively. Also, fermented wheat diets had greater (P < 0.05)
      metabolizable energy content and tended to have greater (P <= 0.10) net energy
      content than unfermented wheat diets. However, inclusion of fermented barley did
      not increase nutrient and energy digestibility. Hetero-fermented diets contained
      greater (P < 0.05) digestible energy and net energy content (DM basis) than Homo
      fermented diets. Pigs fed barley-based diets showed less (P < 0.05) ATTD of DM,
      nitrogen, and gross energy than those fed wheat-based diets. In conclusion, wheat
      fermented with Lactobacillus-inoculum can be beneficially substituted for
      unfermented wheat, improving the ATTD of nutrient and energy, nitrogen retention,
      and energy content. Also, Hetero-inoculum is preferable to Homo-inoculum for
      grain fermentation considering greater energy content in weaned pigs.

PMID- 30184096
TI  - Learning to health yourself: a randomized, tailored self-regulation intervention
      among custodial employees.
AB  - This intervention sought to bring about a dietary behavior change among
      individuals who are vulnerable to negative health outcomes and behaviors. Using a
      randomized controlled trial, we examined the efficacy of a six-week Education +
      Self-Regulation intervention against an Education Only condition in reducing
      saturated fat intake among custodial workers (N = 54). Assessments were made at
      baseline, 4 weeks, 6 weeks and 6 months. The intervention group reported lower
      saturated fat intake and greater self-regulation than the Education Only control
      group throughout the intervention period and higher self-efficacy at week 6.
      Despite a fading of intervention effect at 6 months, Education + Self-Regulation
      participants continued to report lower saturated fat intake relative to their
      baseline. Supplementing health education with self-regulatory skills is an
      effective strategy for positive health behavior change. The authors provide
      recommendations for engaging non-clinical health psychologists in community-level
      chronic disease prevention and health promotion efforts.

PMID- 30184095
TI  - Adaptive Evolution of Animal Proteins over Development: Support for the Darwin
      Selection Opportunity Hypothesis of Evo-Devo.
AB  - A driving hypothesis of evolutionary developmental biology is that animal
      morphological diversity is shaped both by adaptation and by developmental
      constraints. Here, we have tested Darwin's "selection opportunity" hypothesis,
      according to which high evolutionary divergence in late development is due to
      strong positive selection. We contrasted it to a "developmental constraint"
      hypothesis, according to which late development is under relaxed negative
      selection. Indeed, the highest divergence between species, both at the
      morphological and molecular levels, is observed late in embryogenesis and
      postembryonically. To distinguish between adaptation and relaxation hypotheses,
      we investigated the evidence of positive selection on protein-coding genes in
      relation to their expression over development, in fly Drosophila melanogaster,
      zebrafish Danio rerio, and mouse Mus musculus. First, we found that genes
      specifically expressed in late development have stronger signals of positive
      selection. Second, over the full transcriptome, genes with evidence for positive
      selection trend to be expressed in late development. Finally, genes involved in
      pathways with cumulative evidence of positive selection have higher expression in
      late development. Overall, there is a consistent signal that positive selection
      mainly affects genes and pathways expressed in late embryonic development and in
      adult. Our results imply that the evolution of embryogenesis is mostly
      conservative, with most adaptive evolution affecting some stages of postembryonic
      gene expression, and thus postembryonic phenotypes. This is consistent with the
      diversity of environmental challenges to which juveniles and adults are exposed.

PMID- 30184097
TI  - On the adaptive value of monomorphic versus dimorphic enantiostyly in Solanum
      rostratum.
AB  - Background and Aims: Enantiostyly is a reproductive system with heteromorphic
      flowers characterized by asymmetrical deflection of the style, either to the left
      or to the right of the floral axis. There are two types of enantiostyly. In
      monomorphic enantiostyly, plants produce the two types of flowers in the same
      individual. Dimorphic enantiostyly is restricted to only seven species and their
      populations consist of individuals producing either the right or the left flower
      type. It is hypothesized that the dimorphic form is derived from monomorphic
      ancestors because it functions as an outcrossing mechanism. We tested this latter
      hypothesis and investigated if monomorphic enantiostyly is resistant to invasion
      by individuals with dimorphic enantiostyly, because it functions as a
      reproductive assurance mechanism. Methods: To determine the conditions favouring
      the invasion of dimorphic enantiostyly, measurements of reproductive success and
      outcrossing rates in 15 natural flowering patches of Solanum rostratum were made.
      To test if monomorphic enantiostyly provides a reproductive assurance mechanism,
      experimental plants with either manually created dimorphic or natural monomorphic
      reproductive systems were exposed to two different pollination scenarios (flower
      density treatments), and reproductive success and outcrossing rates were
      measured. Key Results: Naturally flowering patches experienced severe pollination
      limitation, showed marked differences in reproductive success and had relatively
      high outcrossing rates. Plants in the experimental patches also showed
      pollination limitation and high outcrossing rates. Individuals with dimorphic
      enantiostyly expressed higher reproductive and outcrossing advantages under high
      density conditions. These advantages disappeared in the low-density treatment,
      where the monomorphic form attained a higher reproductive success and no
      differences in outcrossing rates were detected. Conclusions: Monomorphic
      enantiostyly should be resistant to invasion of the dimorphic form because the
      prevalent ecological conditions favour the maintenance of geitonogamous
      individuals that are able to take advantage of ecological heterogeneity and
      generalized pollination limitation.

PMID- 30184098
TI  - Size matters in STEMI: time for translation of ticagrelor?

PMID- 30184099
TI  - Advancing Control of Cholera in the Interest of the Most Vulnerable in our Global
      Society.

PMID- 30184101
TI  - Effects of ammonia on apoptosis and oxidative stress in bovine mammary epithelial
      cells.
AB  - Ammonia, produced mainly from the deamination of amino acids and glutamine, is
      one of the major toxic components in blood and tissues that may affect bovine
      health. However, the physiological and pathological roles of ammonia in the
      mammary glands are not understood clearly. In the present study, the bovine
      mammary epithelial cell line (MAC-T) was utilised as an in vitro model to
      determine the effects of ammonia on bovine mammary gland. We demonstrated that
      ammonia stimulated the production of intracellular reactive oxygen species,
      decreased mitochondrial membrane potential, interrupted intracellular calcium ion
      (Ca2+) homeostasis and induced cell apoptosis. Ammonia also significantly reduced
      cell viability and increased the proportion of apoptotic cells through enhancing
      the level of p53 phosphorylation and increasing the expressions of BAX, caspase
      8, caspase 9, caspase 3. Interestingly, bumetanide, a specific Na+ K+ 2Cl-
      cotransporter inhibitor, dramatically abolished the damaging effects of ammonia
      on the cells. These data suggest that ammonia exposure induces apoptosis in
      bovine mammary epithelial cells via activation of the p53 pathway and the
      mitochondrial apoptotic pathway, and that these effects involved the Na+ K+ 2Cl-
      cotransporter.

PMID- 30184100
TI  - Colorectal Cancer-derived Small Extracellular Vesicles Establish an Inflammatory
      Pre-metastatic Niche in Liver Metastasis.
AB  - Liver metastases develop in more than half of patients with colorectal cancer
      (CRC) and are associated with a poor prognosis. The factors influencing liver
      metastasis of CRC are poorly characterized, but this information is urgently
      needed. We have now discovered that small extracellular vesicles (sEVs, exosomes)
      derived from CRC can be specifically targeted to liver tissue and induce liver
      macrophage polarization toward an interleukin-6 (IL-6)-secreting pro-inflammatory
      phenotype. More importantly, we found that microRNA-21-5p (miR-21) was highly
      enriched in CRC-derived sEVs and was essential for creating a liver pro
      inflammatory phenotype and liver metastasis of CRC. Silencing either miR-21 in
      CRC-sEVs or Toll-like receptor 7 (TLR7) in macrophages, to which miR-21 binds,
      abolished CRC-sEVs' induction of pro-inflammatory macrophages. Furthermore, miR
      21 expression in plasma-derived sEVs was positively correlated with liver
      metastasis in CRC patients. Collectively, our data demonstrate a pivotal role of
      CRC-sEVs in promoting liver metastasis by inducing an inflammatory pre-metastatic
      niche through the miR-21-TLR7-IL6 axis. Thus, sEVs-miR-21 represents a potential
      prognostic marker and therapeutic target for CRC patients with liver metastasis.

PMID- 30184102
TI  - Global Cholera Epidemiology: Opportunities to Reduce the Burden of Cholera by
      2030.
AB  - While safe drinking water and advanced sanitation systems have made the Global
      North cholera-free for decades, the disease still affects 47 countries across the
      globe resulting in an estimated 2.86 million cases and 95,000 deaths per year
      worldwide. Cholera impacts communities already burdened by conflict, lack of
      infrastructure, poor health systems, and malnutrition. In October 2017, the
      Global Task Force on Cholera Control (GTFCC) launched an initiative titled Ending
      Cholera: A Global Roadmap to 2030, with the objective to reduce cholera deaths by
      90% worldwide, and eliminate cholera in at least 20 countries by 2030. The GTFCC
      is working to position cholera control not as a vertical programme but instead
      using cholera as a marker of inequity and an indicator of poverty, linking the
      objectives of the Roadmap to the SDGs. The roadmap consists of targeted multi
      sectoral interventions, supported by a coordination mechanism, along 3 axes: (1)
      early detection and quick response to contain outbreaks; (2) a multisectoral
      approach to prevent cholera recurrence in hotspots; (3) an effective partnership
      mechanism of coordination for technical support, countries capacity building,
      research and M&E, advocacy and resource mobilization. Every case and every death
      from cholera is preventable with the tools we have today.

PMID- 30184104
TI  - Antiretroviral concentrations in hair strongly predict virologic response in a
      large HIV treatment-naive clinical trial.
AB  - Hair concentrations of antiretrovirals are associated with virologic outcomes in
      cohorts of HIV-positive individuals but have never before been examined in a
      clinical trial. We show for the first time the predictive utility of hair
      antiretroviral concentrations in a large HIV treatment-naive trial, AIDS Clinical
      Trials Group (ACTG) protocol A5257.

PMID- 30184103
TI  - An Ancestry Informative Marker Set Which Recapitulates the Known Fine Structure
      of Populations in South Asia.
AB  - The inference of genomic ancestry using ancestry informative markers (AIMs) can
      be useful for a range of studies in evolutionary genetics, biomedical research,
      and forensic analyses. However, the determination of AIMs for highly admixed
      populations with complex ancestries has remained a formidable challenge. Given
      the immense genetic heterogeneity and unique population structure of the Indian
      subcontinent, here we sought to derive AIMs that would yield a cohesive and
      faithful understanding of South Asian genetic origins. To discern the most
      optimal strategy for extracting AIMs for South Asians we compared three commonly
      used AIMs-determining methods namely, Infocalc, FST, and Smart Principal
      Component Analysis with ADMIXTURE, using previously published whole genome data
      from the Indian subcontinent. Our findings suggest that the Infocalc approach is
      likely most suitable for delineation of South Asian AIMs. In particular, Infocalc
      2,000 (N = 2,000) appeared as the most informative South Asian AIMs panel that
      recapitulated the finer structure within South Asian genomes with high degree of
      sensitivity and precision, whereas a negative control with an equivalent number
      of randomly selected markers when used to interrogate the South Asian
      populations, failed to do so. We discuss the utility of all approaches under
      evaluation for AIMs derivation and interpreting South Asian genomic ancestries.
      Notably, this is the first report of an AIMs panel for South Asian ancestry
      inference. Overall these findings may aid in developing cost-effective resources
      for large-scale demographic analyses and foster expansion of our knowledge of
      human origins and disease, in the South Asian context.

PMID- 30184105
TI  - Effects of letrozole and clomiphene citrate on Wnt signaling pathway in
      endometrium of polycystic ovarian syndrome and healthy women.
AB  - Polycystic ovary syndrome (PCOS) is an endocrine disorder in women of
      reproductive age. In addition to anovulation, endometrial dysfunction can reduce
      fertility in PCOS. The cyclical changes of endometrium are controlled by estrogen
      and progesterone via modulating Wnt/B-catenin pathway. Clomiphene citrate (CC)
      and letrozole are used to induce ovulation; unlike letrozole, there is a
      discrepancy between ovulation and pregnancy rates in CC-treated cycles. Because
      of the anti-estrogenic effects of CC on endometrium, we compared the expression
      of the key molecules of Wnt/B-catenin pathway in the endometrium of women taking
      CC and letrozole. This study included PCOS and healthy women divided into the
      groups stimulated with letrozole (5 mg) or CC (100 mg) as well as NO-treatment
      groups. The endometrial thickness and hormonal profile were measured on day 12 of
      the menses.Using real-time polymerase chain reaction and western blot, we
      evaluated mRNA and protein expression of B-catenin, glycogen synthase kinase 3
      beta (GSK3B), dickkopf Wnt signaling pathway inhibitor 1 (DKK1), and estrogen
      receptor 1 (ESR1) in the endometrial samples. Significantly, the mean serum
      estrogen and progesterone were lower and higher, respectively, in letrozole than
      CC groups. The endometrial thickness was significantly reduced in CC. The
      proteins expression of active B-catenin, inactive GSK3B, and ESR1 were
      significantly decreased in CC-treated groups. The mRNA and protein assessment of
      DKK1 showed significantly higher expression in CC. Our results indicate that
      letrozole can provide an acceptable activation of Wnt/B-catenin pathway,
      resulting in adequate proliferation of endometrium in the women receiving
      letrozole compared to CC.

PMID- 30184106
TI  - Bayesian inference of ancestral dates on bacterial phylogenetic trees.
AB  - The sequencing and comparative analysis of a collection of bacterial genomes from
      a single species or lineage of interest can lead to key insights into its
      evolution, ecology or epidemiology. The tool of choice for such a study is often
      to build a phylogenetic tree, and more specifically when possible a dated
      phylogeny, in which the dates of all common ancestors are estimated. Here, we
      propose a new Bayesian methodology to construct dated phylogenies which is
      specifically designed for bacterial genomics. Unlike previous Bayesian methods
      aimed at building dated phylogenies, we consider that the phylogenetic
      relationships between the genomes have been previously evaluated using a standard
      phylogenetic method, which makes our methodology much faster and scalable. This
      two-step approach also allows us to directly exploit existing phylogenetic
      methods that detect bacterial recombination, and therefore to account for the
      effect of recombination in the construction of a dated phylogeny. We analysed
      many simulated datasets in order to benchmark the performance of our approach in
      a wide range of situations. Furthermore, we present applications to three
      different real datasets from recent bacterial genomic studies. Our methodology is
      implemented in a R package called BactDating which is freely available for
      download at https://github.com/xavierdidelot/BactDating.

PMID- 30184107
TI  - Function of the amino-terminal region of human MCM4 in helicase activity.
AB  - The amino-terminal region of eukaryotic MCM4 is characteristic of the presence of
      a number of phosphorylation sites for CDK and DDK, suggesting that the region
      plays regulatory roles in the MCM2-7 helicase function. However, the roles are
      not fully understood. We analyzed the role of the amino-terminal region of human
      MCM4 by using MCM4/6/7 helicase as a model for MCM2-7 helicase. First we found
      that deletion of 35 amino acids at the amino-terminal end resulted in inhibition
      of DNA helicase activity of the MCM4/6/7 complex. Conversion of arginine at amino
      acid no. 10 and 11 to alanine had similar effect to the deletion mutant of Delta1
      35, suggesting that these arginine play a role in the DNA helicase activity. The
      data suggest that expression of these mutant MCM4 in HeLa cells perturbed the
      progression of the S phase. Substitution of six CDK phosphorylation sites (3, 7,
      19, 32, 54 and 110) in the amino-terminal region by phospho-mimetic glutamic
      acids affected the hexamer formation of the MCM4/6/7 complex. MCM4
      phosphorylation by CDK may play a role in DNA replication licensing system, and
      the present results suggest that the phosphorylation interferes MCM function by
      lowering stability of MCM complex.

PMID- 30184109
TI  - An omega-3 polyunsaturated fatty acid derivative, 18-HEPE, protects against CXCR4
      associated melanoma metastasis.
AB  - Melanoma has a high propensity to metastasize and exhibits a poor response to
      classical therapies. Dysregulation of the chemokine receptor gene CXCR4 is
      associated with melanoma progression, and although n-3 polyunsaturated fatty
      acids (PUFAs) are known to be beneficial for melanoma prevention, the underlying
      mechanism of this effect is unclear. Here, we used the n-3 fatty acid desaturase
      (Fat-1) transgenic mouse model of endogenous n-3 PUFA synthesis to investigate
      the influence of elevated n-3 PUFA levels in a mouse model of metastatic
      melanoma. We found that relative to wild-type (WT) mice, Fat-1 mice exhibited
      fewer pulmonary metastatic colonies and improved inflammatory indices, including
      reduced serum TNF-alpha levels and pulmonary myeloperoxidase activity.
      Differential PUFA metabolites in serum were considered a key factor to alter
      cancer cell travelling to lung and we found that n-6 PUFAs such as arachidonic
      acid induced CXCR4 protein expression while n-3 PUFAs such as EPA decreased CXCR4
      levels. In addition, serum levels of the bioactive eicosapentaenoic acid (EPA)
      metabolite, 18-HEPE, were elevated in Fat-1 mice relative to WT mice, and 18-HEPE
      suppressed CXCR4 expression in B16-F0 cells. Moreover, relative to controls,
      numbers of pulmonary metastatic colonies were reduced in WT mice receiving
      intravenous injections either of 18-HEPE or 18-HEPE-pretreated melanoma cells.
      Our results indicate that 18-HEPE is a potential anticancer metabolite that
      mediates, at least in part, the preventive effect of n-3 PUFA on melanoma
      metastasis.

PMID- 30184108
TI  - Ultrasonographic measurements in first trimester concepti identify predictors of
      birth weight and postnatal development in cattle.
AB  - The placenta is a major driver of prenatal growth and involved in programming of
      postnatal performance. We therefore determined placental and embryo-fetal
      ultrasonographic parameters in early pregnancy and their relationships with birth
      weight and postnatal weights in a Bos indicus-Bos taurus composite beef cattle
      population. Pregnancies were generated in 2-yr-old Droughtmaster heifers by
      artificial insemination after estrus synchronization in 2 consecutive years
      (2009, n = 36 and 2010, n = 57), with a subset of 2010 heifers used again as
      lactating 3-yr-old cows in 2011 (n = 24). Each cohort was managed as 1
      contemporary group for measurements of Corpus luteum diameter, amnion length and
      width, placentome width and thickness, and embryo-fetal crown-rump length, at 7
      and 8 wk of gestation. This was followed by recordings of birth weight, branding
      weight at 5 to 6 mo of age and weaning weight 2 mo later. At a significance
      threshold of P < 0.05, placentome thickness at week 7 was negatively correlated
      with weights at birth (r = -0.23), branding (r = -0.25), and weaning (r = -0.35),
      whereas placentome width at week 7 (r = 0.24) and thickness at week 8 (r = 0.29)
      were positively correlated with birth weight. Thicker placentomes in males at
      week 7 (7%) difference mirrored sex differences in weights at birth (7%),
      branding (10%), and weaning (6%). The sex difference trend for birth weight was
      not consistent across sire-year combinations, ranging from -3.2 to +4.7 kg (birth
      weight of males - females per sire). These results support the hypothesis that
      placental parameters at the transition from embryo to fetal stage are major
      predictors of fetal and postnatal growth, albeit with significant environmentally
      induced plasticity, in stabilized B. indicus-B. taurus composite populations, and
      suggest that elements of B. indicus-B. taurus reciprocal differences in birth
      weight persist in composite populations.

PMID- 30184110
TI  - Thrombin Exosite 1 Inhibition with JNJ-64179375 Inhibits Thrombus Formation in a
      Human Translational Model of Thrombosis.
AB  - Aims: JNJ-64179375 (hereafter JNJ-9375) is a first-in-class, highly specific,
      large molecule, exosite 1 thrombin inhibitor. In preclinical studies, JNJ-9375
      demonstrated robust antithrombotic protection with a wider therapeutic index when
      compared to apixaban. The purpose of the present study was to examine for the
      first time the antiplatelet, anticoagulant and antithrombotic effects of JNJ-9375
      in a translational model of ex vivo human thrombosis. Methods and Results:
      Fifteen healthy volunteers participated in a double-blind randomized crossover
      study of JNJ-9375 (2.5, 25 and 250 MUg/mL), bivalirudin (6 MUg/mL; positive
      control) and matched placebo. Coagulation, platelet activation and thrombus
      formation were determined using coagulation assays, flow cytometry and an ex vivo
      perfusion chamber respectively. JNJ-9375 caused concentration-dependent
      prolongation of all measures of blood coagulation (prothrombin time, activated
      partial thromboplastin time, thrombin time; p < 0.001 for all) and agonist
      selective inhibition of thrombin (0.1 U/mL) stimulated platelet p-selectin
      expression (p < 0.001) and platelet-monocyte aggregates (p = 0.002). Compared to
      placebo, JNJ-9375 (250 MUg/mL) reduced mean total thrombus area by 41.1% (95%
      confidence intervals, 22.3 to 55.3%; p < 0.001) at low shear and 32.3% (4.9 to
      51.8%; p = 0.025) at high shear. Under both shear conditions, there was a dose
      dependent decrease in fibrin-rich thrombus (p < 0.001 for both) but not platelet
      rich thrombus (p=ns for both). Conclusion: Exosite 1 inhibition with JNJ-9375
      caused prolongation of blood coagulation, selective inhibition of thrombin
      mediated platelet activation, and reductions in ex vivo thrombosis driven by a
      decrease in fibrin-rich thrombus formation. JNJ-9375 represents a novel class of
      anticoagulant with potential therapeutic applications.

PMID- 30184111
TI  - Molecular differential diagnosis of uterine leiomyomas and leiomyosarcomas.
AB  - Uterine leiomyomas (LM) and leiomyosarcomas (LMS) are considered biologically
      unrelated tumors due to their cytogenetic and molecular disparity. Yet, these
      tumors share morphological and molecular characteristics that cannot be
      differentiated through current clinical diagnostic tests, and thus cannot be
      definitively classified as benign or malignant until surgery. Newer approaches
      are needed for the identification of these tumors, as has been done for other
      tissues. The application of next generation sequencing (NGS) enables the
      detection of new mutations that, when coupled to machine learning bioinformatic
      tools, advances our understanding of chromosomal instability. These approaches in
      the context of LM and LMS could allow the discovery of genetic variants and
      possible genomic markers. Additionally, the potential clinical utility of
      circulating cell-free tumor DNA (cftDNA) could revolutionize the non-invasive
      detection and monitoring of these tumors. Here, we seek to provide a perspective
      on the molecular background of LM and LMS, recognizing their distinct molecular
      features that may lead to improved diagnosis and personalized treatments, which
      would have a measurable impact on women's reproductive health.

PMID- 30184113
TI  - Is xylem of angiosperm leaves less resistant to embolism than branches? Insights
      from microCT, hydraulics, and anatomy.
AB  - According to the hydraulic vulnerability segmentation hypothesis, leaves are more
      vulnerable to decline of hydraulic conductivity than branches, but whether stem
      xylem is more embolism resistant than leaves remains unclear. Drought-induced
      embolism resistance of leaf xylem was investigated based on X-ray microcomputed
      tomography (microCT) for Betula pendula, Laurus nobilis, and Liriodendron
      tulipifera, excluding outside-xylem, and compared with hydraulic vulnerability
      curves for branch xylem. Moreover, bordered pit characters related to embolism
      resistance were investigated for both organs. Theoretical P50 values (i.e. the
      xylem pressure corresponding to 50% loss of hydraulic conductance) of leaves were
      generally within the same range as hydraulic P50 values of branches. P50 values
      of leaves were similar to branches for L. tulipifera (-2.01 versus -2.10 MPa,
      respectively), more negative for B. pendula (-2.87 versus -1.80 MPa), and less
      negative for L. nobilis (-6.4 versus -9.2 MPa). Despite more narrow conduits in
      leaves than branches, mean interconduit pit membrane thickness was similar in
      both organs, but significantly higher in leaves of B. pendula than in branches.
      This case study indicates that xylem shows a largely similar embolism resistance
      across leaves and branches, although differences both within and across organs
      may occur, suggesting interspecific variation with regard to the hydraulic
      vulnerability segmentation hypothesis.

PMID- 30184112
TI  - Intragenic Meiotic Crossovers Generate Novel Alleles with Transgressive
      Expression Levels.
AB  - Meiotic recombination is an evolutionary force that generates new genetic
      diversity upon which selection can act. Whereas multiple studies have assessed
      genome-wide patterns of recombination and specific cases of intragenic
      recombination, few studies have assessed intragenic recombination genome-wide in
      higher eukaryotes. We identified recombination events within or near genes in a
      population of maize recombinant inbred lines (RILs) using RNA-sequencing data.
      Our results are consistent with case studies that have shown that intragenic
      crossovers cluster at the 5' ends of some genes. Further, we identified cases of
      intragenic crossovers that generate transgressive transcript accumulation
      patterns, that is, recombinant alleles displayed higher or lower levels of
      expression than did nonrecombinant alleles in any of ~100 RILs, implicating
      intragenic recombination in the generation of new variants upon which selection
      can act. Thousands of apparent gene conversion events were identified, allowing
      us to estimate the genome-wide rate of gene conversion at SNP sites (4.9 * 10-5).
      The density of syntenic genes (i.e., those conserved at the same genomic
      locations since the divergence of maize and sorghum) exhibits a substantial
      correlation with crossover frequency, whereas the density of nonsyntenic genes
      (i.e., those which have transposed or been lost subsequent to the divergence of
      maize and sorghum) shows little correlation, suggesting that crossovers occur at
      higher rates in syntenic genes than in nonsyntenic genes. Increased rates of
      crossovers in syntenic genes could be either a consequence of the evolutionary
      conservation of synteny or a biological process that helps to maintain synteny.

PMID- 30184114
TI  - Bioaerosol Sampling to Detect Avian Influenza Virus in Hanoi's Largest Live
      Poultry Market.
AB  - Background: Newly emergent and virulent strains of H7N9 avian influenza virus are
      rapidly spreading in China and threaten to invade Vietnam. We sought to introduce
      aerosol sampling for avian influenza viruses in Vietnam. Methods: During October
      2017, National Institute for Occupational Safety and Health 2-stage aerosol
      samplers were assembled on a tripod and run for 4 hours. Concomitantly, up to 20
      oropharyngeal (OP) swab samples were collected from chickens and ducks distanced
      at 0.2-1.5 m from each sampler. Results: The 3 weeks of sampling yielded 30
      aerosol samples that were 90% positive for influenza A, by quantitative reverse
      transcription polymerase chain reaction, and 116 OP swab sample pools (5 samples
      per pool) that were 47% positive. Egg cultures yielded 1 influenza A virus (not
      H5 or H7) from aerosol and 25 influenza A viruses from OP swab sample pools (5
      were H5 positive). The association between positive sample types (over time and
      position) was strong, with 91.7% of positive OP pooled swab samples confirmed by
      positive aerosol samples and 81% of influenza A positive aerosol samples
      confirmed by positive OP swab samples. Conclusions: We posit that aerosol
      sampling might be used for early warning screening of poultry markets for novel
      influenza virus detection, such as H7N9. Markets with positive aerosol samples
      might be followed up with more focused individual bird or cage swabbing, and back
      tracing could be performed later to locate specific farms harboring novel virus.
      Culling birds in such farms could reduce highly pathogenic avian influenza virus
      spread among poultry and humans.

PMID- 30184115
TI  - Identification of reliable reference genes for quantitative real-time PCR in lung
      and heart of pulmonary hypertensive chickens.
AB  - Accurate normalization in real-time quantitative PCR is an important step in
      quantification of gene transcription pattern, in which proper application of
      stable reference gene(s) is crucial. To identify the most stable reference gene
      (s) in pulmonary hypertensive chickens, from a panel of 9 typical candidate
      genes, the expression of ACTB, HMBS, HPRT1, RPL13, RPL32, 18SrRNA, TBP, TFRC, and
      YWHAZ was determined in the lung and heart (right ventricle) of both healthy and
      cold-induced pulmonary hypertensive chickens at 42 d of age. The BestKeeper,
      geNorm, and NormFinder software programs were used to analyze this set of genes.
      Also, the ratio of right ventricle to the total ventricle was used as an index of
      induced pulmonary hypertension, which increased in the cold-treated chickens
      compared to the control at 42 d of age. Candidate reference genes ranking in the
      lung of pulmonary hypertensive chickens vs. healthy individuals included RPL13,
      YWHAZ, HMBS, ACTB, HPRT1, TFRC, RPL32, 18SrRNA, and TBP; those in the heart were
      YWHAZ, RPL13, HMBS, ACTB, HPRT1, TBP, 18SrRNA, TFRC, and RPL32; and those in the
      heart-lung combination included RPL13, YWHAZ, HMBS, HBRT1, TFRC, ACTB, 18SrRNA,
      RPL32, and TBP. The overall results showed that the most stable genes are YWHAZ,
      RPL13, HMBS, ACTB, HBRT1, TFRC, TBP, RPL32, and 18SrRNA, respectively. In
      addition, the combination of YWHAZ, RPL13, and HMBS is recommended as the
      reference gene panel for more accurate quantitative data normalization of heart
      or lung in the chicken pulmonary hypertension.

PMID- 30184116
TI  - Recent advances in the microbial hydroxylation and reduction of soy isoflavones.
AB  - Soy isoflavones are naturally occurring phytochemicals, which are biotransformed
      into functional derivatives through oxidative and reductive metabolic pathways of
      diverse microorganisms. Such representative derivatives, ortho
      dihydroxyisoflavones (ODIs) and equols, have attracted great attention for their
      versatile health benefits since they were found from soybean fermented foods and
      human intestinal fluids. Recently, scientists in food technology, nutrition and
      microbiology began to understand their correct biosynthetic pathways and
      nutraceutical values, and have attempted to produce the valuable bioactive
      compounds using microbial fermentation and whole-cell/enzyme-based
      biotransformation. Furthermore, artificial design of microbial catalysts and/or
      protein engineering of oxidoreductases were also conducted to enhance production
      efficiency and regioselectivity of products. This minireview summarizes and
      introduces the past year's studies and recent advances in notable production of
      ODIs and equols, and provides information on available microbial species and
      their catalytic performance with perspectives on industrial application.

PMID- 30184117
TI  - Cholera: Immunity and Prospects in Vaccine Development.
AB  - Vibrio cholerae is a prototypical noninvasive mucosal pathogen, yet infection
      generates long-lasting protection against subsequent disease. Vibriocidal
      antibody responses are an imperfect but established correlate of protection
      against cholera following both infection and vaccination. However, vibriocidal
      antibody responses are likely a surrogate marker for longer-lasting functional
      immune responses that target the O-polysaccharide antigen at the mucosal surface.
      While the current bivalent inactivated oral whole cell vaccine is being
      increasingly used to prevent cholera in areas where the disease is a threat, the
      most significant limitation of this vaccine is it offers relatively limited
      direct protection in young children. Future strategies for cholera vaccination
      include the development of cholera conjugate vaccines and the further development
      of live attenuated vaccines. Ultimately, the goal of a multivalent vaccine for
      cholera and other childhood enteric infections that can be incorporated into a
      standard immunization schedule should be realized.

PMID- 30184119
TI  - Spatial and temporal characterization of epiphytic microbial communities
      associated with Eurasian watermilfoil: a highly invasive macrophyte in North
      America.
AB  - Bacterial communities that inhabit the surface of aquatic plants are thought to
      play a critical role in relation to host fitness and function. However, little is
      known about their structure and dynamics in comparison with those of
      bacterioplankton. In this study, we performed a comprehensive spatial and
      temporal characterization of epibacterial communities associated with Eurasian
      watermilfoil (EWM; Myriophyllum spicatum), an invasive macrophyte, which has
      established itself in thousands of lakes across North America. EWM samples were
      collected from 10 lakes in Minnesota, once a month, for six consecutive months,
      along with surrounding water and sediment. High-throughput DNA sequencing
      analyses, performed on all samples (n = 522) using the Illumina platform,
      indicated that EWM-associated epibacterial communities were distinct from those
      found in water and sediment. EWM-specific microbiota was comprised of operational
      taxonomic units classified to the families Rhodobacteraceae, Comamonadaceae,
      Cyanobacteria Subsection I Family I, Aeromonadaceae, Planctomycetaceae,
      Sphingomonadaceae and Verrucomicrobiaceae. In addition, several identified taxa
      were overrepresented in EWM samples when compared to water and sediment. Amongst
      all the environmental factors examined, water temperature had the greatest
      influence on epibacterial community structure. Our findings suggest that EWM
      harbor specific, but temporally adapted, epibacterial communities that are
      potentially involved in host-microbe interactions.

PMID- 30184118
TI  - Vibrio cholerae chromosome 2 copy number is controlled by the methylation
      independent binding of its monomeric initiator to the chromosome 1 crtS site.
AB  - Bacteria contain a primary chromosome and, frequently, either essential secondary
      chromosomes or dispensable megaplasmids of plasmid origin. Incoming plasmids are
      often poorly adapted to their hosts and their stabilization requires integration
      with the host's cellular mechanisms in a process termed domestication. All
      Vibrio, including pathogenic species, carry a domesticated secondary chromosome
      (Chr2) where replication is coordinated with that of the primary chromosome
      (Chr1). Chr2 replication is triggered by the replication of an intergenic
      sequence (crtS) located on Chr1. Yet, the molecular mechanisms by which crtS
      replication controls the initiation of Chr2 replication are still largely
      unknown. In this study, we show that crtS not only regulates the timing of Chr2
      initiation but also controls Chr2 copy number. We observed and characterized the
      direct binding of the Chr2 initiator (RctB) on crtS. RctB binding to crtS is
      independent of its methylation state. RctB molecules, which naturally form
      dimers, preferentially bind to crtS as monomers, with DnaK/J protein chaperones
      shown to stimulate binding of additional RctB monomers on crtS. In this study, we
      addressed various hypothesis of how replication of crtS could trigger Chr2
      replication and provide new insights into its mode of action.

PMID- 30184120
TI  - Exploration of Functional Limitation Codes for Outpatient Physical Therapy in the
      Medicare Population: A Retrospective Cohort Study.
AB  - Background: The Centers for Medicare & Medicaid Services (CMS) introduced
      functional limitation reporting (FLR) to capture patient progress in functional
      status in outpatient rehabilitation settings. FLR along with the severity
      modifier (SM) measure the effectiveness of the rehabilitation services at the
      physical therapist evaluation (initial examination [IE]) after 10 days of therapy
      and at discharge. Objective: The objective of this study was to explore the
      completeness of FLR codes and describe changes in SMs at scheduled checkpoints
      for patients receiving outpatient physical therapy. Design: The design was a
      retrospective cohort descriptive study. Methods: A 5% random sample of 2014 Part
      B fee-for-service Medicare claims for outpatient physical therapy was used. FLR
      codes with SMs were analyzed at required periods. The number of claims with FLR
      codes and SMs was calculated to describe the completeness for each period.
      Planned changes in SMs at the physical therapist IE (current status and projected
      goal status) and differences in SMs from the physical therapist IE (current
      status) to discharge (discharge status) were calculated. Results: For 114,588
      beneficiaries, 166,572 physical therapist IE and 130,117 discharge claims were
      analyzed. Completion was greater than 90% for current status and projected goal
      status FLR codes at the physical therapist IE but was markedly lower for interim
      and discharge reporting (<= 50% for all). More than 75% of claims had planned
      improvements in SMs at the physical therapist IE (projected goal status - current
      status), with variations by specific FLR codes. For the episodes with FLR codes
      at the physical therapist IE and discharge, improvements were reported in more
      than 2 of 3 episodes. Limitations: Limitations for these analyses include a
      missing discharge claim on many outpatient physical therapy episodes and
      potential coding errors with Medicare claims. Conclusions: Except for the
      physical therapist IE, FLR codes were not submitted consistent with regulations.
      Most physical therapy episodes showed improvements in FLR SMs from the physical
      therapist IE and discharge, although the low completion rate limited
      interpretation. Changes to the FLR program are warranted to understand whether
      changes in SMs correspond to changes in a patient's function.

PMID- 30184121
TI  - 5-Formylcytosine mediated DNA-protein cross-links block DNA replication and
      induce mutations in human cells.

PMID- 30184122
TI  - Cesarean section and risks of overweight and obesity in school-aged children: a
      population-based study.
AB  - Background: Obesity puts a great health burden in the world. Previous studies
      suggest that caesarean section (CS) may increase the risk of obesity in children,
      but it is still uncertain whether this association is causal or due to residual
      confounding by medical indication. Aim: To assess the association between CS, CS
      without medical indications in particular and the risk of overweight and obesity
      in school-aged children. Design: Cross-sectional survey. Methods: The 2014
      Shanghai Child Health, Education and Lifestyle Evaluation was a large population
      based survey with cluster random probability sampling in 26 primary schools in
      Shanghai, China, in 2014. The mode of delivery was reported by parents. The
      height, weight and waist circumference of the children were measured. Logistic
      regression models with SURVEYLOGISTIC procedure were used to estimate the risk of
      childhood obesity. Pupils delivered vaginally were served as the reference group.
      Results: A total of 17 571 pupils completed this survey, and 13 724 of them who
      were singleton, born term and between 5 and 13 years old were included in our
      analysis. CS was associated with increased risks of overweight and obesity (BMI:
      adjusted OR = 1.28 [95%CI 1.13-1.45] and 1.44 [1.26-1.66], respectively; weight
      for height ratio [WHtR] >0.46: 1.33 [1.20-1.48]). Similar results were found in
      CS without medical indication (BMI: overweight = 1.24 [1.05-1.47], obesity = 1.43
      [1.19-1.72]; WHtR > 0.46: 1.30 [1.13-1.50]). Conclusions: CS overall and CS
      without medical indications were associated with increased risks of overweight
      and obesity in primary school children.

PMID- 30184123
TI  - Challenges and barriers associated with medication management for home nursing
      clients in Australia: a qualitative study combining the perspectives of community
      nurses, community pharmacists and GPs.
AB  - Background: Increasing numbers of older people are receiving home nursing support
      for medication management to enable them to remain living at home. Home nursing
      clients frequently experience medication errors and adverse medication events.
      There has been little study of how medication management processes and
      interdisciplinary teamwork impact on medication management in the home nursing
      setting. Objective: To explore medication management processes and describe
      barriers and challenges from the perspective of community nurses, community
      pharmacists and GPs involved in the provision of medication management services
      for home nursing clients. Methods: Focus groups, in-depth interviews and
      stakeholder consultations were conducted with a convenience sample of community
      nurses, community pharmacists and GPs. Data were analysed using the framework
      approach (a deductive thematic analysis) to identify issues affecting the
      delivery of medication management services. Results: Ten focus groups, 12 in
      depth interviews and 5 stakeholder consultation meetings were conducted with 86
      health practitioners (55 community nurses, 17 GPs, 10 community pharmacists and 4
      nurse managers). Participants highlighted a range of barriers and challenges
      associated with medication management for home nursing clients, including
      deficiencies in interdisciplinary communication; problems related to
      organizational or workplace policies, processes and systems; and ineffective team
      function. The negative impacts of these were recognized as compromised client
      safety, reduced workforce efficiency and productivity and compromised
      interprofessional relationships. Conclusion: Barriers and challenges with
      medication management for home nursing clients and associated negative impacts
      were identified. Strategies are needed to improve interdisciplinary medication
      management and medication safety in the home nursing setting.

PMID- 30184124
TI  - Editorial: complexity and adaptability: an introduction to the special thematic
      issue on the genus Pseudomonas.

PMID- 30184126
TI  - Genomic Analysis of Picochlorum Species Reveals How Microalgae May Adapt to
      Variable Environments.
AB  - Understanding how microalgae adapt to rapidly changing environments is not only
      important to science but can help clarify the potential impact of climate change
      on the biology of primary producers. We sequenced and analyzed the nuclear genome
      of multiple Picochlorum isolates (Chlorophyta) to elucidate strategies of
      environmental adaptation. It was previously found that coordinated gene
      regulation is involved in adaptation to salinity stress, and here we show that
      gene gain and loss also play key roles in adaptation. We determined the extent of
      horizontal gene transfer (HGT) from prokaryotes and their role in the origin of
      novel functions in the Picochlorum clade. HGT is an ongoing and dynamic process
      in this algal clade with adaptation being driven by transfer, divergence, and
      loss. One HGT candidate that is differentially expressed under salinity stress is
      indolepyruvate decarboxylase that is involved in the production of a plant auxin
      that mediates bacteria-diatom symbiotic interactions. Large differences in levels
      of heterozygosity were found in diploid haplotypes among Picochlorum isolates.
      Biallelic divergence was pronounced in P. oklahomensis (salt plains environment)
      when compared with its closely related sister taxon Picochlorum SENEW3 (brackish
      water environment), suggesting a role of diverged alleles in response to
      environmental stress. Our results elucidate how microbial eukaryotes with limited
      gene inventories expand habitat range from mesophilic to halophilic through
      allelic diversity, and with minor but important contributions made by HGT. We
      also explore how the nature and quality of genome data may impact inference of
      nuclear ploidy.

PMID- 30184125
TI  - Using ruminally protected and nonprotected active dried yeast as alternatives to
      antibiotics in finishing beef steers: growth performance, carcass traits, blood
      metabolites, and fecal Escherichia coli.
AB  - The objective of this study was to evaluate the effects of supplementing the diet
      of finishing beef steers with active dried yeast (ADY) in ruminally protected and
      nonprotected forms on growth performance, carcass traits, and immune response.
      Seventy-five individually-fed Angus steers (initial body weight (BW) +/- SD, 448
      +/- 8.4 kg) were assigned to a randomized complete design with 5 treatments: 1)
      control (no monensin, tylosin, or ADY), 2) antibiotics (ANT, 330 mg monensin +
      110 mg tylosin.steer-1d-1), 3) ADY (1.5 g.steer-1d-1), 4) encapsulated ADY (EDY;
      3 g.steer-1d-1), and 5) a mixture of ADY and EDY (MDY; 1.5 g ADY + 3 g EDY.steer
      1d-1). Active dried yeast with 1.7 * 1010 cfu/g was encapsulated in equal amounts
      of ADY and capsule materials (stearic acid and palm oil). Steers were fed a total
      mixed ration containing 10% barley silage and 90% barley-based concentrate mix
      (dry matter [DM] basis). The ANT, ADY, and EDY were top-dressed daily to the diet
      at feeding. Intake of DM, final BW, averaged daily gain (ADG), and gain-to-feed
      ratio (G:F) were unaffected by ADY or EDY. Carcass traits including hot carcass
      weight (HCW), dressing percentage, marbling score and quality grade did not
      differ among treatments, although fewer severely abscessed livers were observed
      (P < 0.05) with ADY and MDY compared with the other treatments. Plasma urea N
      tended (P < 0.10) to be greater in steers fed ANT, ADY, or EDY on day 56 and 112,
      while glucose remained stable in all treatments except greater (P < 0.02) plasma
      glucose occurred in steers fed MDY on day 112. Serum nonestrified fatty acid
      (NEFA) was unaffected by ADY or EDY, but it was greater (P < 0.03) in steers fed
      ANT compared with control. Plasma haptoglobin (Hp) and serum amyloid A (SAA) were
      affected by yeast supplementation on day 112, with greater (P < 0. 01) Hp in
      steers fed ADY, EDY, or MDY and lesser (P < 0.01) SAA in steers fed EDY and MDY
      than control. Lipopolysaccharide binding protein concentrations were greater (P <
      0.01) in steers fed EDY and MDY on day 56. Supplementing with ADY (protected or
      nonprotected) or ANT had no effect on fecal IgA contents on day 56 and 112.
      Steers fed yeast (EDY or MDY) tended (P < 0.10) to have fewer fecal Escherichia
      coli counts than the control and ANT on day 56 and 112. These results indicate
      that feeding ADY to feedlot cattle may exhibit antipathogenic activity that
      conferred health and food safety beneficial effects including reduced liver
      abscess and potentially pathogen excretion, thus yeast may be an alternative to
      in-feed antibiotics in natural beef cattle production systems.

PMID- 30184128
TI  - Oral administration of viable Bifidobacterium pseudolongum strain Patronus
      modified colonic microbiota and increased mucus layer thickness in rat.
AB  - This study aimed at evaluating the alteration of the colonic microbiota and the
      changes in the mucus layer thickness induced by oral administration of living
      bifidobacteria in rats. The study was performed on rats fed with Bifidobacterium
      pseudolongum strain Patronus (1010 bacteria per day for 7 days). This bacterial
      administration led to a large increase of mucus thickness (57%, P < 0.05). Both
      quantitative PCR and high-throughput sequencing of bacterial 16S rRNA gene
      revealed a significant increase of the amount of the Bifidobacterium genus in the
      microbiota of rats fed with the strain Patronus, associated with a decrease of
      Akkermansia muciniphila. The increase in mucus thickness could be due to an
      increase of the bifidobacteria per se or via the decrease of A. muciniphila, a
      major mucin-degrading species. As the mucus layer plays an essential role in gut
      protection, our data enlighten the importance of studying mucus-degrading
      bacteria for understanding the underlying etiology of diseases such as intestinal
      bowel diseases and to implement new therapeutic strategies.

PMID- 30184129
TI  - Comparison of antidepressant use between adult populations living in urban and
      rural communities in Israel.
AB  - Background: Depression and anxiety are among the most prevalent disorders in
      primary care. City dwelling is commonly cited as a risk factor for mental
      disorders, but epidemiological evidence for this relationship is inconclusive.
      Objective: To compare the prevalence of antidepressant use, as a proxy for the
      level of depressive disorders, between patients in Israeli urban and rural
      communities. Methods: A cross-sectional study, based on data drawn from the
      registry of the largest health maintenance organization in Israel. The prevalence
      of antidepressant purchase during 2014 was evaluated for 581291 patients living
      in urban and rural communities. Data were also collected for potential
      confounding variables: age, gender, comorbidity, socioeconomic status and being a
      holocaust survivor. Results: Results showed higher rates of antidepressant use
      among patients living in urban (11.8%) compared with rural communities (8.1%;
      <0.001). A particularly high rate of antidepressant use was found on kibbutz
      (15.9%), a collective rural community in Israel, compared with both urban and
      other rural communities. Kibbutz compared with other rural communities: odds
      ratio (OR) = 1.73, P < 0.001; urban communities compared with non-kibbutz rural
      communities: OR = 1.21, P < 0.001. A significantly lower rate of antidepressant
      use was found in urban and rural Arab-majority communities (3.9% and 3.8%,
      respectively). Conclusions: Antidepressant use varies significantly between
      different communities in Israel. The highest rate of antidepressant use in our
      study was found on kibbutz, followed by that in urban communities, with the
      lowest rates in non-kibbutz rural communities. This difference may derive from
      different depression rates, stigma of mental illness and awareness of mental
      disorders.

PMID- 30184127
TI  - Fe-S Cluster Assembly in Oxymonads and Related Protists.
AB  - The oxymonad Monocercomonoides exilis was recently reported to be the first
      eukaryote that has completely lost the mitochondrial compartment. It was proposed
      that an important prerequisite for such a radical evolutionary step was the
      acquisition of the SUF Fe-S cluster assembly pathway from prokaryotes, making the
      mitochondrial ISC pathway dispensable. We have investigated genomic and
      transcriptomic data from six oxymonad species and their relatives, composing the
      group Preaxostyla (Metamonada, Excavata), for the presence and absence of enzymes
      involved in Fe-S cluster biosynthesis. None possesses enzymes of mitochondrial
      ISC pathway and all apparently possess the SUF pathway, composed of SufB, C, D,
      S, and U proteins, altogether suggesting that the transition from ISC to SUF
      preceded their last common ancestor. Interestingly, we observed that SufDSU were
      fused in all three oxymonad genomes, and in the genome of Paratrimastix
      pyriformis. The donor of the SUF genes is not clear from phylogenetic analyses,
      but the enzyme composition of the pathway and the presence of SufDSU fusion
      suggests Firmicutes, Thermotogae, Spirochaetes, Proteobacteria, or Chloroflexi as
      donors. The inventory of the downstream CIA pathway enzymes is consistent with
      that of closely related species that retain ISC, indicating that the switch from
      ISC to SUF did not markedly affect the downstream process of maturation of
      cytosolic and nuclear Fe-S proteins.

PMID- 30184130
TI  - Large-scale purification of ovalbumin using polyethylene glycol precipitation and
      isoelectric precipitation.
AB  - In addition to small amounts of minerals and carbohydrates, most of the dry
      matter of chicken egg white is protein, making egg white an ideal resource for
      obtaining food proteins. Ovalbumin (OVA), which accounts for more than 50% of the
      total egg white protein, is one of the most widely studied food proteins due to
      its multiple functional properties, and it has also been used as a model protein
      molecule in many research fields. The objective of this study was to develop a
      simple and rapid method for the purification of OVA from egg whites on large
      scale. First, OVA was separated from ovomucin, ovotransferrin, and ovomucoid by
      polyethylene glycol (PEG) concentration, using the following optimal parameters:
      the PEG concentration was 15%, the pH was 6.5, the salt concentration was 100
      mmol/L, and the operating temperature was 10 degrees C. The OVA-rich supernatant
      obtained from PEG precipitation was further purified by isoelectric precipitation
      at a pI of 4.5 and a temperature of 4 degrees C, and the purified OVA was
      obtained with at a purity of 95.1% by HPLC, with a yield of 46.4%. After the
      extraction of OVA, the PEG solution was vacuum dried and then utilized cyclically
      in the PEG precipitation steps. The whole purification process could be finished
      within 2 to 3 h at a scale of several kilograms of egg white. This method has the
      advantages of rapidity, simplicity, low cost, and ease of scalability.

PMID- 30184131
TI  - Corrigendum to "Comparing two techniques for viscosity measurements in poultry
      feedstuffs: does it render similar conclusions?"

PMID- 30184132
TI  - Reliability, Validity, and Responsiveness of Clinical Performance-Based Outcome
      Measures of Walking for Individuals With Lower Limb Amputations: A Systematic
      Review.
AB  - Background: Clinical outcome measures are important to use for individuals with
      lower limb amputations (LLA) because such individuals require intensive
      functional gait training before and after being fitted with prostheses. Using
      standardized instruments throughout the episode of care allows clinicians to
      objectively monitor patient progress, make evidence-based decisions regarding the
      plan of care, and communicate results in meaningful ways to patients, payers, and
      other clinicians. Many clinical outcome measures exist, but not all have been
      validated and shown to be reliable within this population of interest. Purpose:
      The aim of this review was to provide a comprehensive overview of the
      psychometric properties of all current performance-based outcome measures
      applicable to individuals with lower limb amputations. Data Sources: Reviewers
      searched for articles using the online databases PubMed/MEDLINE and CINAHL.
      Reviewers also conducted a manual search of the reference list of 1 of the
      previously published systematic reviews to identify any additional studies not
      detected with the online database search. Study Selection: The 2 reviewers
      screened titles and abstracts for relevance. The same reviewers obtained and read
      full-text articles of the potentially relevant studies. Reviewers resolved any
      discrepancies of the inclusion assessment by further discussion. Data Extraction:
      The reviewers created tables to extract psychometric properties of interest from
      the included articles. Both reviewers extracted the data from the articles and
      placed relevant values into a table for each primary outcome measure identified.
      Data Synthesis: The rigor of study reporting was guided by use of the
      Strengthening the Reporting of Observational Studies in Epidemiology (STROBE)
      Checklist. Each reviewer independently read and appraised the included articles,
      assigning a score to each checklist item. The sum of scores for each item was
      calculated to appraise the overall quality of reporting of the included articles.
      Limitations: Review-level limitations included the absence of a third reviewer to
      settle any disagreements on article inclusion and article appraisal.
      Additionally, the percentage of reviewer agreement on article appraisal was not
      determined before disagreements about checklist item satisfaction were resolved.
      Furthermore, reviewers only extracted data on reliability, validity, and
      responsiveness; instrument characteristics, such as floor and ceiling effects,
      are also important. Conclusions: Valid and reliable performance-based clinical
      measures of ambulation in individuals with LLA were identified. Further research
      should investigate the minimally clinical, important difference of these clinical
      measures and address trends in unmet reporting guidelines.

PMID- 30184133
TI  - Neurophysiological Changes Associated with Antidepressant Response to Ketamine
      Not Observed in a Negative Trial of Scopolamine in Major Depressive Disorder.
AB  - Background: This randomized, placebo-controlled, crossover trial examined the
      antidepressant efficacy of the muscarinic antagonist scopolamine in major
      depressive disorder subjects with more severe and refractory forms of major
      depressive disorder relative to previous reports. Methods: Participants included
      23 medication-free major depressive disorder subjects (12 F/11 M, 20-55 years)
      currently experiencing a major depressive episode. Subjects had scored >=20 on
      the Montgomery-Asberg Depression Rating Scale. Following a single-blind, placebo
      lead-in, participants were randomized to receive 2 counterbalanced blocks of 3
      i.v. infusions of scopolamine (4 MUg/kg) and placebo in a double-blind manner.
      The primary and secondary outcomes were the Montgomery-Asberg Depression Rating
      Scale and the Hamilton Anxiety Rating Scale, respectively. Magnetoencephalography
      and plasma brain-derived neurotrophic factor concentrations were obtained prior
      to and after each treatment phase. Results: As assessed by both the Montgomery
      Asberg Depression Rating Scale and Hamilton Anxiety Rating Scale, scopolamine had
      no significant antidepressant or anxiolytic effects relative to placebo. No
      significant drug vs placebo effects were seen in magnetoencephalography gamma
      power or brain-derived neurotrophic factor plasma concentrations, and brain
      derived neurotrophic factor changes did not correlate with change in Montgomery
      Asberg Depression Rating Scale score in response to scopolamine. Conclusions:
      These results do not support the efficacy of scopolamine for more severe or
      refractory forms of depression. No pre- to post-infusion changes in plasma brain
      derived neurotrophic factor were detected, and magnetoencephalography gamma power
      changed only in the placebo lead-in, suggesting that these biomarker measures
      were not affected by scopolamine in this cohort. While difficult to interpret
      given the lack of antidepressant response, the findings suggest that the
      neurobiological effects of ketamine and scopolamine are at least partly distinct.

PMID- 30184134
TI  - Myo-inositol as an adjuvant to florfenicol against Aeromonas hydrophila infection
      in common carp Cyprinus carpio.
AB  - Florfenicol, a synthetic drug with chemical structure and spectrum of
      antibacterial activity similar to chloramphenicol, has been shown to be effective
      against a number of bacterial pathogens. However, there are increasing signs of
      florfenicol-resistant bacteria due to the misuse and overuse of florfenicol in
      aquaculture. In the present study, florfenicol had a higher bactericidal efficacy
      in the presence of myo-inositol, which may be due to the ability of myo-inositol
      to increase susceptibility of Aeromonas hydrophila to florfenicol. Furthermore,
      in two different infected models, co-administration of myo-inositol and
      florfenicol significantly reduced the bacterial load in the liver, kidney and
      spleen tissues of A. hydrophila-infected Cyprinus carpio, and greatly increased
      the survival rate of infected fish. Finally, it was also found that myo-inositol
      exhibited synergistic action with other antibiotic drugs including neomycin
      sulfate, ceftriaxone and enrofloxacin. The results obtained in this study suggest
      that myo-inositol as an efficient adjuvant to antibiotic drugs could be useful in
      increasing the antimicrobial activity of antibiotic drugs against A. hydrophila
      infection, and could also be useful to help decrease the occurrence of antibiotic
      overuse in aquaculture.

PMID- 30184136
TI  - Corrigendum.

PMID- 30184135
TI  - A limited number of double-strand DNA breaks is sufficient to delay cell cycle
      progression.
AB  - DNA damaging agents cause a variety of lesions, of which DNA double-strand breaks
      (DSBs) are the most genotoxic. Unbiased approaches aimed at investigating the
      relationship between the number of DSBs and outcome of the DNA damage response
      have been challenging due to the random nature in which damage is induced by
      classical DNA damaging agents. Here, we describe a CRISPR/Cas9-based system that
      permits us to efficiently introduce DSBs at defined sites in the genome. Using
      this system, we show that a guide RNA targeting only a single site in the human
      genome can trigger a checkpoint response that is potent enough to delay cell
      cycle progression. Abrogation of this checkpoint leads to DNA breaks in mitosis
      which gives rise to aneuploid progeny.

PMID- 30184137
TI  - Commentary: Tobacco smoking and asthma: multigenerational effects, epigenetics
      and multilevel causal mediation analysis.

PMID- 30184138
TI  - Extended-spectrum cephalosporin-resistant Escherichia coli isolated from chickens
      and chicken meat in Brazil is associated with rare and complex resistance
      plasmids and pandemic ST lineages.
AB  - Objectives: Brazil is the greatest exporter of chicken meat (CM) in the world. It
      is of utmost importance to monitor resistance to extended-spectrum cephalosporins
      (ESCs) in this sector because resistance to ESCs in Escherichia coli isolated
      from food-producing animals may contaminate humans through the food chain. Thus,
      the aim of this study was to characterize and compare ESC-resistant E. coli
      isolated from chickens and retail CM produced in south-eastern Brazil. Methods:
      Five CM samples and 117 chicken cloacal swabs (CCSs) were inoculated on MacConkey
      agar supplemented with cefotaxime. Presumptive E. coli colonies were identified
      and antimicrobial susceptibility was tested. Virulence and acquired blaESBL and
      blaAmpC genes were sought and genetic environments characterized. Isolates were
      typed by phylogenetic grouping, XbaI-PFGE and MLST. Results: All five CM samples
      and 36 CCSs (30.8%) were positive for the presence of ESC-resistant E. coli,
      leading to the selection of 58 resistant isolates. ESC resistance was mostly due
      to the presence of the chromosome-encoded blaCTX-M-2 gene, but plasmid-mediated
      blaCTX-M-2, blaCTX-M-8, blaCTX-M-15, blaCTX-M-55 and blaCMY-2 were also detected.
      Multireplicon plasmids were sporadically identified, such as IncHI2/P-blaCTX-M-2
      and IncFII/N-blaCTX-M-55. Phylogroup D predominated, while PFGE and MLST revealed
      a high genetic diversity. Conclusions: Live Brazilian chickens and CM act as
      reservoirs of ESC-resistant E. coli and resistance genes are located on highly
      diverse genetic determinants. Potentially pathogenic strains, which may represent
      a threat to human health and a source of environmental contamination, were also
      identified. Active surveillance is therefore essential in Brazil's chicken
      production line.

PMID- 30184139
TI  - Effects of organic zinc on tibia quality, mineral deposit, and metallothionein
      expression level of aged hens.
AB  - The study aimed to determine the effects of methionine hydroxy analog chelate
      zinc on the tibia quality, mineral deposit, apparent retention of nutrients, and
      liver metallothionein (MT) expression level of aged laying hens. A total of 960
      layers (Hy-Line Grey, 57 wk old) were randomly assigned into 4 groups, and each
      group had 8 replicates of 30 hens. During the first 2 wk, groups were fed a basal
      diet without extra zinc (Zn: 35.08 mg/kg). During the ensuing 14 wk, 4 levels of
      Zn (inorganic Zn: 80 mg/kg; organic Zn: 20, 40, 80 mg/kg) were added to the diet.
      The results indicated that both the Zn source and level did influence tibia
      strength and calcium (Ca) and Zn concentrations of tibia (P < 0.05), whereas
      there were no differences in the copper (Cu) and phosphorus (P) concentrations of
      the tibia and the tibia length (P > 0.05). Moreover, dietary supplementation with
      40 or 80 mg/kg of organic Zn showed higher Zn and Ca concentrations in the tibia
      and higher tibia strength. The Cu concentration in the liver showed no difference
      among the 4 treatments, whereas the Zn concentration in the liver increased with
      the increasing Zn level. The apparent retention of P, iron (Fe), and manganese
      (Mn) was not affected by the Zn level or source (P > 0.05). However, the organic
      Zn group increased the apparent retention of Cu, Zn, Ca, crude protein (CP), and
      energy, and the group supplemented with 40 or 80 mg/kg of organic Zn obtained
      significant effects (P < 0.05). Moreover, dietary supplementation with 40 or 80
      mg/kg organic Zn increased the MT mRNA expression of the liver at week 72,
      whereas 20 mg/kg of organic Zn decreased it (P < 0.05). In conclusion, this study
      suggested that an optimum dietary (40 mg/kg) organic Zn level plays a key role in
      promoting the apparent retention of minerals and nutrients, trace element
      deposit, and MT mRNA expression.

PMID- 30184142
TI  - Sequential DNA immunization of chickens with bivalent heterologous vaccines
      induce highly reactive and cross-specific antibodies against influenza
      hemagglutinin.
AB  - Vaccines against avian influenza are mostly based on hemagglutinin (HA), which is
      the main antigen of this virus and a target for neutralizing antibodies.
      Traditional vaccines are known to be poorly efficient against newly emerging
      strains, which is an increasing worldwide problem for human health and for the
      poultry industry. As demonstrated by research and clinical data, sequential
      exposure to divergent influenza HAs can boost induction of universal antibodies
      which recognize conserved epitopes. In this work, we have performed sequential
      immunization of laying hens using monovalent or bivalent compositions of DNA
      vaccines encoding HAs from distant groups 1 and 2 (H5, H1, and H3 subtypes,
      respectively). This strategy gave promising results, as it led to induction of
      polyclonal antibodies against HAs from both groups. These polyclonal antibodies
      showed cross-reactivity between different HA strains in ELISA, especially when
      bivalent formulations were used for immunization of birds. However, cross
      reactivity of antibodies induced against H3 and H5 HA subtypes was rather limited
      against each other after homologous immunization. Using a cocktail of HA
      sequences and/or sequential DNA vaccination with different strains presents a
      good strategy to overcome the limited effectiveness of vaccines and induce
      broader immunity against avian influenza. Such a strategy could be adapted for
      vaccinating laying hens or parental flocks of different groups of poultry.

PMID- 30184143
TI  - Corrigendum.

PMID- 30184141
TI  - From Treatment Response to Recovery: A Realistic Goal in OCD.
AB  - Despite longitudinal studies reporting symptomatic remission rates ranging from
      32% to 70%, Obsessive-Compulsive Disorder is considered a persistent and very
      disabling disorder. However, these studies suggest that recovery can be a
      realistic goal for a subgroup of the Obsessive-Compulsive Disorder population and
      that a clear definition of recovery is timely in Obsessive-Compulsive Disorder.
      The aim of this paper is to discuss the dimensions of and propose an operational
      definition of recovery in Obsessive-Compulsive Disorder. Considering the impact
      generated by the definition of recovery for other mental disorders, this article
      discusses how this concept may shape the future of research and clinical practice
      in Obsessive-Compulsive Disorder. Ultimately, the hope is that the management of
      Obsessive-Compulsive Disorder may parallel, and expand upon, some of the current
      approaches implemented in the care of schizophrenia, so that early diagnosis,
      stepped-care techniques, and a personalized approach can be used to create
      recovery-oriented treatment programs and influence policy making for Obsessive
      Compulsive Disorder.

PMID- 30184140
TI  - sppIDer: A Species Identification Tool to Investigate Hybrid Genomes with High
      Throughput Sequencing.
AB  - The genomics era has expanded our knowledge about the diversity of the living
      world, yet harnessing high-throughput sequencing data to investigate alternative
      evolutionary trajectories, such as hybridization, is still challenging. Here we
      present sppIDer, a pipeline for the characterization of interspecies hybrids and
      pure species, that illuminates the complete composition of genomes. sppIDer maps
      short-read sequencing data to a combination genome built from reference genomes
      of several species of interest and assesses the genomic contribution and relative
      ploidy of each parental species, producing a series of colorful graphical outputs
      ready for publication. As a proof-of-concept, we use the genus Saccharomyces to
      detect and visualize both interspecies hybrids and pure strains, even with
      missing parental reference genomes. Through simulation, we show that sppIDer is
      robust to variable reference genome qualities and performs well with low-coverage
      data. We further demonstrate the power of this approach in plants, animals, and
      other fungi. sppIDer is robust to many different inputs and provides visually
      intuitive insight into genome composition that enables the rapid identification
      of species and their interspecies hybrids. sppIDer exists as a Docker image,
      which is a reusable, reproducible, transparent, and simple-to-run package that
      automates the pipeline and installation of the required dependencies
      (https://github.com/GLBRC/sppIDer; last accessed September 6, 2018).

PMID- 30184144
TI  - Myectomy with mitral valve repair versus replacement in adult patients with
      hypertrophic obstructive cardiomyopathy: a systematic review and meta-analysis.
AB  - We evaluated the differences in mitral valve (MV) plasty (MVP) and MV replacement
      (MVR) with respect to death, postoperative MV dysfunction, reoperation rates and
      thromboembolic events (DFRE) in patients with hypertrophic obstructive
      cardiomyopathy and systolic anterior motion of the anterior mitral leaflet
      mediated MV regurgitation (HOCM & MR). We followed the Preferred Reporting Items
      for Systematic Reviews and Meta-analyses guidelines, searching PubMed, Cochrane
      library and ClinicalTrials.gov for studies that evaluated DFRE in adults with
      HOCM & MR after MVP/MVR. We used a risk of bias assessment tool for non
      randomized studies, and analyses were performed using Cochrane Review Manager
      5.3.5 for I2 statistics, funnel plots and forest plot and the generic inverse
      variance method for hazard ratios (HRs). We developed qualitative and
      quantitative syntheses of 35 and 23 studies, respectively, including levels of
      evidence of 1/2/3/4/5 = 3/1/11/11/9 and 1/2/3/4/5 = 0/1/11/11/0, respectively,
      from January 1980 to August 2017. A statistically significant difference between
      MVP and MVR favoured MVP for the prevention of DFRE in patients with HOCM & MR,
      on the basis of a significant reduction of the HR for DFRE: HR = 0.68 (0.57,
      0.82), I2 = 68% (P = 0.002). The findings were as follows: (i) MVP should be the
      first-line treatment in patients with HOCM & MR (accuracy LEVEL A) and (ii) MVR
      may be harmful if it is used as the first-line treatment (accuracy LEVEL A).

PMID- 30184145
TI  - Computational determination of gene age and characterization of evolutionary
      dynamics in human.
AB  - Genes originate at different evolutionary time scales and possess different ages,
      accordingly presenting diverse functional characteristics and reflecting distinct
      adaptive evolutionary innovations. In the past decades, progresses have been made
      in gene age identification by a variety of methods that are principally based on
      comparative genomics. Here we summarize methods for computational determination
      of gene age and evaluate the effectiveness of different computational methods for
      age identification. Our results show that improved age determination can be
      achieved by combining homolog clustering with phylogeny inference, which enables
      more accurate age identification in human genes. Accordingly, we characterize
      evolutionary dynamics of human genes based on an extremely long evolutionary time
      scale spanning ~4,000 million years from archaea/bacteria to human, revealing
      that young genes are clustered on certain chromosomes and that Mendelian disease
      genes (including monogenic disease and polygenic disease genes) and cancer genes
      exhibit divergent evolutionary origins. Taken together, deciphering genes' ages
      as well as their evolutionary dynamics is of fundamental significance in
      unveiling the underlying mechanisms during evolution and better understanding how
      young or new genes become indispensable integrants coupled with novel phenotypes
      and biological diversity.

PMID- 30184147
TI  - Acroosteolysis in a patient with systemic lupus erythematosus/mixed connective
      tissue disease.

PMID- 30184146
TI  - NCCN Asia Consensus Statement prostate cancer.
AB  - The National Comprehensive Cancer Network, an NPO organization comprised of
      university hospitals and cancer centers in the US. The publication of clinical
      practice guidelines on the treatment, diagnosis, prevention and screening is one
      of important activities. Background factors of prostate cancer patients, such as
      the prevalence, age at the diagnosis and mortality are markedly different between
      Western countries and Asia. Thus, various factors should be taken into
      consideration at the treatment choice for individual patients. Experts from Asian
      countries were published as the Asia Consensus Statement. In this review, we
      explain important points of the Asia Consensus Statement such as differences in
      the epidemiological backgrounds of patients, differences in treatment options and
      differences in medical insurance systems.

PMID- 30184148
TI  - Adjuvant treatment of high-risk renal cell carcinoma: the jury is still out.

PMID- 30184149
TI  - 1918 H1N1 Influenza Virus Infection-Induced Proinflammatory Cytokines in the
      Olfactory Bulb Could Trigger Lethargic Disease.

PMID- 30184150
TI  - TRCirc: a resource for transcriptional regulation information of circRNAs.
AB  - In recent years, high-throughput genomic technologies like chromatin
      immunoprecipitation sequencing (ChIp-seq) and transcriptome sequencing (RNA-seq)
      have been becoming both more refined and less expensive, making them more
      accessible. Many circular RNAs (circRNAs) that originate from back-spliced exons
      have been identified in various cell lines across different species. However, the
      regulatory mechanism for transcription of circRNAs remains unclear. Therefore,
      there is an urgent need to construct a database detailing the transcriptional
      regulation of circRNAs. TRCirc (http://www.licpathway.net/TRCirc) provides a
      resource for efficient retrieval, browsing and visualization of transcriptional
      regulation information of circRNAs. The current version of TRCirc documents 92
      375 circRNAs and 161 transcription factors (TFs) from more than 100 cell types
      and together represent more than 765 000 TF-circRNA regulatory relationships.
      Furthermore, TRCirc provides other regulatory information about transcription of
      circRNAs, including their expression, methylation levels, H3K27ac signals in
      regulation regions and super-enhancers associated with circRNAs. TRCirc provides
      a convenient, user-friendly interface to search, browse and visualize detailed
      information about these circRNAs.

PMID- 30184151
TI  - A framework to support risk assessment in hospitals.
AB  - Quality problem or issue: A number of challenges have been identified with
      current risk assessment practice in hospitals, including: a lack of consultation
      with a sufficiently wide group of stakeholders; a lack of consistency and
      transparency; and insufficient risk assessment guidance. Consequently, risk
      assessment may not be fully effective as a means to ensure safety. Initial
      assessment: We used a V system developmental model, in conjunction with mixed
      methods, including interviews and document analysis to identify user needs and
      requirements. Choice of solution: One way to address current challenges is
      through providing good guidance on the fundamental aspects of risk assessment. We
      designed a risk assessment framework, comprising: a risk assessment model that
      depicts the main risk assessment steps; risk assessment explanation cards that
      provide prompts to help apply each step; and a risk assessment form that helps to
      systematize the risk assessment and document the findings. Implementation: We
      conducted multiple group discussions to pilot the framework through the use of a
      representative scenario and used our findings for the user evaluation.
      Evaluation: User evaluation was conducted with 10 participants through interviews
      and showed promising results. Lessons learned: While the framework was
      recommended for use in practice, it was also proposed that it be adopted as a
      training tool. With its use in risk assessment, we anticipate that risk
      assessments would lead to more effective decisions being made and more
      appropriate actions being taken to minimize risks. Consequently, the quality and
      safety of care delivered could be improved.

PMID- 30184152
TI  - SUMO-1 modification of FEN1 facilitates its interaction with Rad9-Rad1-Hus1 to
      counteract DNA replication stress.
AB  - Human flap endonuclease 1 (FEN1) is a structure-specific, multi-functional
      endonuclease essential for DNA replication and repair. We and others have shown
      that during DNA replication, FEN1 processes Okazaki fragments via its interaction
      with the proliferating cell nuclear antigen (PCNA). Alternatively, in response to
      DNA damage, FEN1 interacts with the PCNA-like Rad9-Rad1-Hus1 complex instead of
      PCNA to engage in DNA repair activities, such as homology-directed repair of
      stalled DNA replication forks. However, it is unclear how FEN1 is able to switch
      between these interactions and its roles in DNA replication and DNA repair. Here,
      we report that FEN1 undergoes SUMOylation by SUMO-1 in response to DNA
      replication fork-stalling agents, such as UV irradiation, hydroxyurea, and
      mitomycin C. This DNA damage-induced SUMO-1 modification promotes the interaction
      of FEN1 with the Rad9-Rad1-Hus1 complex. Furthermore, we found that FEN1
      mutations that prevent its SUMO-1 modification also impair its ability to
      interact with HUS1 and to rescue stalled replication forks. These impairments
      lead to the accumulation of DNA damage and heightened sensitivity to fork
      stalling agents. Altogether, our findings suggest an important role of the SUMO-1
      modification of FEN1 in regulating its roles in DNA replication and repair.

PMID- 30184153
TI  - Viral Etiology of Acute Gastroenteritis in <2-Year-Old US Children in the Post
      Rotavirus Vaccine Era.
AB  - Background: The rotavirus disease burden has declined substantially since
      rotavirus vaccine was introduced in the United States in 2006. The aim of this
      study was to determine the viral etiology of acute gastroenteritis (AGE) in US
      children aged <2 years. Methods: The New Vaccine Surveillance Network (NVSN) of
      geographically diverse US sites conducts active pediatric population-based
      surveillance in hospitals and emergency departments. Stool samples were collected
      from children aged <2 years with symptoms of AGE (n = 330) and age-matched
      healthy controls (HCs) (n = 272) between January and December 2012. Samples were
      tested by real-time reverse-transcriptase polymerase chain reaction assays
      {adenovirus (type 40 and 41), norovirus, parechovirus A, enterovirus, sapovirus,
      and astrovirus} and an enzyme immunoassay (rotavirus). All samples that tested
      positive were genotyped. Results: Detection rates of pathogens in children with
      AGE versus those of HCs were, respectively, 23.0% versus 6.6% for norovirus (P <
      .01), 23.0% versus 16.0% for adenovirus (P = .08), 11.0% versus 16.0% for
      parechovirus A (P = .09), 11.0% versus 9.0% for enterovirus (P = .34), 7.0%
      versus 3.0% for sapovirus (P = .07), 3.0% versus 0.3% for astrovirus (P = .01),
      and 3.0% versus 0.4% for rotavirus (P = .01). A high prevalence of adenovirus was
      detected at 1 surveillance site (49.0% for children with AGE and 43.0% for HCs).
      Norovirus GII.4 New Orleans was the most frequently detected (33.0%) norovirus
      genotype. Codetection of >1 virus was more common in children with AGE (16.0%)
      than in HCs (10.0%) (P = .03). Conclusions: Norovirus, astrovirus, sapovirus, and
      rotavirus were detected significantly more in children with AGE than in HCs, and
      norovirus was the leading AGE-causing pathogen in US children aged <2 years
      during the year 2012.

PMID- 30184155
TI  - Alterations in cellular and viral microRNA and cellular gene expression in
      Marek's disease virus-transformed T-cell lines treated with sodium butyrate.
AB  - A shared feature of herpesviruses is their ability to enter a latent state
      following an initially lytic infection. Marek's disease virus serotype 1 (MDV-1)
      is an oncogenic avian herpesvirus. Small RNA profiling studies have suggested
      that microRNAs (miRNAs) are involved in viral latency. Sodium butyrate treatment
      is known to induce herpesvirus reactivation. The present study was undertaken to
      determine transcriptome and miRNome changes induced by sodium butyrate in 2 MDV
      transformed cell lines, RP2 and CU115. In the first 24 h post-treatment,
      microarray analysis of transcriptional changes in cell lines RP2 and CU115
      identified 137 and 114 differentially expressed genes, respectively. Small RNA
      deep-sequencing analysis identified 17 cellular miRNAs that were differentially
      expressed. The expression of MDV-encoded miRNAs was also altered upon treatment.
      Many of the genes and miRNAs that are differentially expressed are involved in
      regulation of the cell cycle, mitosis, DNA metabolism, and lymphocyte
      differentiation.

PMID- 30184154
TI  - Effects of phytogenic additives on meat quality traits in broiler chickens.
AB  - Phytogenics have been reported to improve growth performances in farm animals and
      are thereby considered as potential key solutions for antibiotic-free livestock
      nutrition. Yet, their effects on meat quality are still not well defined;
      therefore, the aim of this study was to determine the effects of 5 experimental
      phytogenic additives (3 dietary and 2 water supplements) on growth and meat
      quality in broilers. One-day-old broiler chicks (n = 576) were assigned to 48
      floor pens and divided into 6 treatments (Control, AV/HGP/16 premix [AVHGP],
      Superliv concentrate premix [SCP], bacteriostatic herbal growth promotor [BHGP],
      AV/SSL/12 [AVSSL], and Superliv Gold [SG]) in a complete randomized design (8
      pens/treatment with 12 birds/pen, and 96 birds/group). Feed intake and BW were
      recorded, and birds were processed at 42 d to evaluate carcass traits. Breast
      muscle tissues were excised to determine stress- and antioxidant-related genes
      expression. Both AVSSL- and SG-treated broilers produced heavier (P < 0.05)
      slaughter weights compared with the control-fed broilers, whereas AVSSL
      supplementation decreased (P < 0.05) fat pad size and increased (P < 0.05) breast
      weights compared with the control-fed broilers. Although pH and a* values
      remained unchanged, L* was decreased (P < 0.05) in all treatment and b* was
      reduced (P < 0.05) in SG when compared with controls. The trained sensory
      panelists detected more (P < 0.05) green herb flavor in the breast meat from
      AVHGP than SCP, SG, and control birds. The expression of superoxide dismutase 2,
      extracellular signal-regulated kinase 1/2, and JNK gene was upregulated in AVHGP
      and BHGP compared with the control (P < 0.05). Together, these results indicated
      that phytogenic additives might improve meat quality of broilers through
      modulation of stress- and antioxidant-related pathways.

PMID- 30184156
TI  - The 21st Century Cures Act and electronic health records one year later: will
      patients see the benefits?
AB  - While federal regulation provides patients the right to access their electronic
      health records and promotes increased use of health information technology,
      patient access to electronic health records remains limited. The 21st Century
      Cures Act, signed into law over a year ago, has important provisions that could
      significantly improve access and availability of health data. Specifically, the
      provisions call for partnerships among health information exchange networks,
      educational and research initiatives, and health information technology
      certification requirements that encourage interoperability. The article reviews
      the potential benefits and concerns regarding implementation of these provisions,
      particularly the difficulty of aligning incentives and requirements for data
      sharing and the question of whether currently proposed rules and guidance will
      support the goal of improved patient access and health information exchange.
      Researchers, clinicians, and patients have the power to advocate for improved
      patient access and interoperability as policy development and implementation of
      the 21st Century Cures Act continues.

PMID- 30184157
TI  - Sharing data from electronic health records within, across, and beyond healthcare
      institutions: Current trends and perspectives.

PMID- 30184158
TI  - From Child Protection to Paradigm Protection-The Genesis, Development, and
      Defense of a Scientific Paradigm.
AB  - A scientific paradigm typically embraces research norms and values, such as truth
      seeking, critical thinking, disinterestedness, and good scientific practice.
      These values should prevent a paradigm from introducing defective assumptions.
      But sometimes, scientists who are also physicians develop clinical norms that are
      in conflict with the scientific enterprise. As an example of such a conflict, we
      have analyzed the genesis and development of the shaken baby syndrome (SBS)
      paradigm. The point of departure of the analysis is a recently conducted
      systematic literature review, which concluded that there is very low scientific
      evidence for the basic assumption held by Child Protection Teams: when certain
      signs are present (and no other "acceptable" explanations are provided) the
      infant has been violently shaken. We suggest that such teams have developed more
      value-based than scientific-based criteria when classifying SBS cases. Further,
      we suggest that the teams are victims of "groupthink," aggravating the
      difficulties in considering critics' questioning the criteria established by the
      teams.

PMID- 30184159
TI  - Alcohol Consumption and the Risk of Gastroesophageal Reflux Disease: A Systematic
      Review and Meta-analysis.
AB  - Aims: Epidemiologic evidence on alcohol consumption increasing the risk of
      gastroesophageal reflux disease (GERD) is contradictory. This study aimed to
      investigate the correlation between alcohol consumption and GERD by a meta
      analysis of observational studies. Short summary: Gastroesophageal reflux disease
      (GERD) is a prevalent disease, and the incidence is rising. We conducted a meta
      analysis of observational studies, indicating that there was a significant
      association between alcohol consumption and the risk of GERD. This finding
      provides important implications for the prevention and control of GERD. Methods:
      Two investigators retrieved relevant studies on PubMed, Cochrane and EMBASE,
      respectively. The summary odds ratios (ORs) and 95% confidence intervals (CIs)
      were calculated by random effects model to assess the association. Heterogeneity
      was quantified using the Q statistic and I2. Subgroup analysis, publication bias
      and sensitivity analysis were also conducted. Results: Twenty-six cross-sectional
      studies and three case-control studies were included in the meta-analysis. The
      pooled random effects OR was 1.48 (95%CI, 1.31-1.67; I2 = 88.8%), in comparison
      between drinkers and non-/occasional drinkers. For reflux esophagitis and non
      erosive reflux disease, two subtypes of GERD, the ORs were 1.78 (95%CI, 1.56
      2.03; I2 = 87.5%) and 1.15 (95%CI, 1.04-1.28; I2 = 0.3%), respectively. In
      addition, the pooled OR for drinkers who drank <3-5 times or days per week was
      1.29 (95%CI, 1.14-1.46; I2 = 35.5%), while for those who drank more frequently,
      the OR was 2.12 (95%CI, 1.63-2.75; I2 = 55.1%). Dose-response analysis showed a
      linear association between alcohol consumption and GERD (Pfornonlinearity=0.235).
      The pooled OR for a 12.5 g/day increment of alcohol was 1.16 (95%CI, 1.07-1.27; P
      = 0.001). Conclusions: This meta-analysis provides evidence for a potential
      association between alcohol drinking and the risk of GERD. The increase in
      alcohol consumption and frequency showed a stronger association with GERD.

PMID- 30184161
TI  - Masquerading as pea plants: behavioural and morphological evidence for mimicry of
      multiple models in an Australian orchid.
AB  - Background and Aims: While there is increasing recognition of Batesian floral
      mimicry in plants, there are few confirmed cases where mimicry involves more than
      one model species. Here, we test for pollination by mimicry in Diuris
      (Orchidaceae), a genus hypothesized to attract pollinators via mimicry of a range
      of co-occurring pea plants (Faboideae). Methods: Observations of pollinator
      behaviour were made for Diuris brumalis using arrays of orchid flowers. An
      analysis of floral traits in the co-flowering community and spectral reflectance
      measurements were undertaken to test if Di. brumalis and the pea plants showed
      strong similarity and were likely to be perceived as the same by bees. Pollen
      removal and fruit-set were recorded at 18 sites over two years to test if fitness
      of Di. brumalis increased with the abundance of the model species. Key Results:
      Diuris brumalis shares the pollinator species Trichococolletes capillosus and T.
      leucogenys (Hymenoptera: Colletidae) with co-flowering Faboideae from the genus
      Daviesia. On Di. brumalis, Trichocolletes exhibited the same stereotyped food
      foraging and mate-patrolling behaviour that they exhibit on Daviesia. Diuris and
      pea plants showed strong morphological similarity compared to the co-flowering
      plant community, while the spectral reflectance of Diuris was similar to that of
      Daviesia spp. Fruit-set and pollen removal of Di. brumalis was highest at sites
      with a greater number of Daviesia flowers. Conclusions: Diuris brumalis is
      pollinated by mimicry of co-occurring congeneric Faboideae species. Evidence for
      mimicry of multiple models, all of which share pollinator species, suggests that
      this may represent a guild mimicry system. Interestingly, Di. brumalis belongs to
      a complex of species with similar floral traits, suggesting that this represents
      a useful system for investigating speciation in lineages that employ mimicry of
      food plants.

PMID- 30184162
TI  - Integrating Facility-Based Surveillance With Healthcare Utilization Surveys to
      Estimate Enteric Fever Incidence: Methods and Challenges.
AB  - Cohort studies and facility-based sentinel surveillance are common approaches to
      characterizing infectious disease burden, but present trade-offs; cohort studies
      are resource-intensive and may alter disease natural history, while sentinel
      surveillance underestimates incidence in the population. Hybrid surveillance,
      whereby facility-based surveillance is paired with a community-based healthcare
      utilization assessment, represents an alternative approach to generating
      population-based disease incidence estimates with moderate resource investments.
      Here, we discuss this method in the context of the Surveillance for Enteric Fever
      in Asia Project (SEAP) study. We describe how data are collected and utilized to
      adjust enteric fever incidence for blood culture sensitivity, facility-based
      enrollment, and healthcare seeking, incorporating uncertainty in these parameters
      in the uncertainty around incidence estimates. We illustrate how selection of
      surveillance sites and their coverage may influence precision and bias, and we
      identify approaches in the study design and analysis to minimize and control for
      these biases. Rigorously designed hybrid surveillance systems can be an efficient
      approach to generating population-based incidence estimates for infectious
      diseases.

PMID- 30184163
TI  - Corrigendum: A transcriptome-based resolution for a key taxonomic controversy in
      Cupressaceae.

PMID- 30184166
TI  - Estimation and Validation of Flour Exposure in Bakeries in Alberta, Canada.
AB  - Objectives: In epidemiological studies of work-related ill-health only current
      exposures can, at best, be measured. Previous exposures may be estimated using
      contemporaneous hygiene records or published data. This study aimed to create a
      job exposure matrix for exposure in bakers for use in an ongoing cohort study.
      Methods: A systematic review was conducted of English language publications on
      exposures in bakeries. All publications that appeared to contain quantitative
      measures of exposure to flour dust, wheat allergen, or fungal alpha-amylase were
      read independently by two investigators and relevant data extracted. A third
      investigator reviewed these data and publications were retained that reported
      full-shift exposures to inhalable dust, wheat allergen, or alpha-amylase, and for
      which geometric means (GMs) were given or could be estimated. For each study, the
      number of sampling results contributing to each GM was recorded together with
      information on task, bakery size, product, filter type, sampling head, the
      country in which the study was conducted, and the estimated year of sampling.
      Multivariable models were elaborated for each exposure using a linear mixed
      effects approach. The predictive capacity of the model for inhaled particles was
      tested against samples collected in eight Alberta bakeries. The capacity of
      exposure intensity, estimated from each of the three models, to predict
      sensitization was tested against skin prick testing (SPT) for bakery allergens in
      bakers currently employed in Alberta. Results: One thousand three hundred and
      ninety-seven publications were identified through the systematic search, of which
      27 had data used to create one or more of the predictive models. Weighted GMs
      were used as outcome variables. For inhalable dust, task, bakery size, type of
      sampling head, and year of sampling contributed to the final model. For wheat
      allergen and alpha-amylase, task, bakery size, sampling head, and year of
      sampling again contributed. Product (bread rather than confectionary or mixed
      products) was also important in these two latter measures. The model for
      inhalable dust was used to predict the concentration in 33 samples from Alberta
      bakeries. Overall, 91% of observed samples had 95% confidence intervals (CIs)
      overlapping the 95% CIs of the predicted values. A model including the Alberta
      samples found no effect attributable to Alberta provenance. Using this model for
      inhalable dust and the models developed solely from the literature for wheat
      allergen and alpha-amylase, a positive SPT for bakery allergens in 57 bakers
      recruited for this study was significantly related to log cumulative exposure for
      each of the three outcome variables and to log exposure intensity for wheat
      allergen and alpha-amylase. Conclusions: The exposure models developed from the
      literature provide useful estimates of exposure. Calibration of the models
      against locally collected samples may be useful for countries poorly represented
      in the modeling dataset.

PMID- 30184164
TI  - Transposase subunit architecture and its relationship to genome size and the rate
      of transposition in prokaryotes and eukaryotes.
AB  - Cut-and-paste transposons are important tools for mutagenesis, gene-delivery and
      DNA sequencing applications. At the molecular level, the most thoroughly
      understood are Tn5 and Tn10 in bacteria, and mariner and hAT elements in
      eukaryotes. All bacterial cut-and-paste transposases characterized to date are
      monomeric prior to interacting with the transposon end, while all eukaryotic
      transposases are multimers. Although there is a limited sample size, we proposed
      that this defines two pathways for transpososome assembly which distinguishes the
      mechanism of the bacterial and eukaryotic transposons. We predicted that the
      respective pathways would dictate how the rate of transposition is related to
      transposase concentration and genome size. Here, we have tested these predictions
      by creating a single-chain dimer version of the bacterial Tn5 transposase. We
      show that artificial dimerization switches the transpososome assembly pathway
      from the bacterial-style to the eukaryotic-style. Although this had no effect in
      vitro, where the transposase does not have to search far to locate the transposon
      ends, it increased the rate of transposition in bacterial and HeLa cell assays.
      However, in contrast to the mariner elements, the Tn5 single-chain dimer remained
      unaffected by over-production inhibition, which is an emergent property of the
      transposase subunit structure in the mariner elements.

PMID- 30184165
TI  - Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate is Non-inferior to
      Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate in Treatment-naive Adults
      With Human Immunodeficiency Virus-1 Infection: Week 48 Results of the DRIVE-AHEAD
      Trial.
AB  - Background: Doravirine (DOR), a novel non-nucleoside reverse-transcriptase
      inhibitor (NNRTI), is active against wild-type Human Immunodeficiency Virus (HIV)
      1 and the most common NNRTI-resistant variants, and has a favorable and unique in
      vitro resistance profile. Methods: DRIVE-AHEAD is a phase 3, double-blind, non
      inferiority trial. Antiretroviral treatment-naive adults with >=1000 HIV-1 RNA
      copies/mL were randomized (1:1) to once-daily, fixed-dose DOR at 100 mg,
      lamivudine at 300 mg, and tenofovir disoproxil fumarate (TDF) at 300 mg
      (DOR/3TC/TDF) or to efavirenz at 600 mg, emtricitabine at 200 mg, and TDF at 300
      mg (EFV/FTC/TDF) for 96 weeks. The primary efficacy endpoint was the proportion
      of participants with <50 HIV-1 RNA copies/mL at week 48 (Food and Drug
      Administration snapshot approach; non-inferiority margin 10%). Results: Of the
      734 participants randomized, 728 were treated (364 per group) and included in the
      analyses. At week 48, 84.3% (307/364) of DOR/3TC/TDF recipients and 80.8%
      (294/364) of EFV/FTC/TDF recipients achieved <50 HIV-1 RNA copies/mL (difference
      3.5%, 95% CI, -2.0, 9.0). DOR/3TC/TDF recipients had significantly lower rates of
      dizziness (8.8% vs 37.1%), sleep disorders/disturbances (12.1% vs 25.2%), and
      altered sensorium (4.4% vs 8.2%) than EFV/FTC/TDF recipients. Mean changes in
      fasting low-density lipoprotein cholesterol (LDL-C) and non-high-density
      lipoprotein cholesterol (non-HDL-C) (-3.83 vs +13.26 mg/dL) were significantly
      different between DOR/3TC/TDF and EFV/FTC/TDF (-1.6 vs +8.7 mg/dL and -3.8 vs
      +13.3 mg/dL, respectively). Conclusions: In HIV-1 treatment-naive adults,
      DOR/3TC/TDF demonstrated non-inferior efficacy to EFV/FTC/TDF at week 48 and was
      well tolerated, with significantly fewer neuropsychiatric events and minimal
      changes in LDL-C and non-HDL-C compared with EFV/FTC/TDF. Clinical Trials
      Registration: www.clinicaltrials.gov, NCT02403674.

PMID- 30184160
TI  - Endocrine Toxicity of Cancer Immunotherapy Targeting Immune Checkpoints.
AB  - Immune checkpoints are small molecules expressed by immune cells that play
      critical roles in maintaining immune homeostasis. Targeting the immune
      checkpoints cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed
      death 1 (PD-1) with inhibitory antibodies has demonstrated effective and durable
      antitumor activity in subgroups of patients with cancer. The US Food and Drug
      Administration has approved several immune checkpoint inhibitors (ICPis) for the
      treatment of a broad spectrum of malignancies. Endocrinopathies have emerged as
      one of the most common immune-related adverse events (irAEs) of ICPi therapy.
      Hypophysitis, thyroid dysfunction, insulin-deficient diabetes mellitus, and
      primary adrenal insufficiency have been reported as irAEs due to ICPi therapy.
      Hypophysitis is particularly associated with anti-CTLA-4 therapy, whereas thyroid
      dysfunction is particularly associated with anti-PD-1 therapy. Diabetes mellitus
      and primary adrenal insufficiency are rare endocrine toxicities associated with
      ICPi therapy but can be life-threatening if not promptly recognized and treated.
      Notably, combination anti-CTLA-4 and anti-PD-1 therapy is associated with the
      highest incidence of ICPi-related endocrinopathies. The precise mechanisms
      underlying these endocrine irAEs remain to be elucidated. Most ICPi-related
      endocrinopathies occur within 12 weeks after the initiation of ICPi therapy, but
      several have been reported to develop several months to years after ICPi
      initiation. Some ICPi-related endocrinopathies may resolve spontaneously, but
      others, such as central adrenal insufficiency and primary hypothyroidism, appear
      to be persistent in most cases. The mainstay of management of ICPi-related
      endocrinopathies is hormone replacement and symptom control. Further studies are
      needed to determine (i) whether high-dose corticosteroids in the treatment of
      ICPi-related endocrinopathies preserves endocrine function (especially in
      hypophysitis), and (ii) whether the development of ICPi-related endocrinopathies
      correlates with tumor response to ICPi therapy.

PMID- 30184167
TI  - Loop permutation affects the topology and stability of G-quadruplexes.
AB  - G-quadruplexes are unusual DNA and RNA secondary structures ubiquitous in a
      variety of organisms including vertebrates, plants, viruses and bacteria. The
      folding topology and stability of intramolecular G-quadruplexes are determined to
      a large extent by their loops. Loop permutation is defined as swapping two or
      three of these regions so that intramolecular G-quadruplexes only differ in the
      sequential order of their loops. Over the past two decades, both length and base
      composition of loops have been studied extensively, but a systematic study on the
      effect of loop permutation has been missing. In the present work, 99 sequences
      from 21 groups with different loop permutations were tested. To our surprise,
      both conformation and thermal stability are greatly dependent on loop
      permutation. Loop permutation actually matters as much as loop length and base
      composition on G-quadruplex folding, with effects on Tm as high as 17 degrees C.
      Sequences containing a longer central loop have a high propensity to adopt a
      stable non-parallel topology. Conversely, sequences containing a short central
      loop tend to form a parallel topology of lower stability. In addition, over half
      of interrogated sequences were found in the genomes of diverse organisms,
      implicating their potential regulatory roles in the genome or as therapeutic
      targets. This study illustrates the structural roles of loops in G-quadruplex
      folding and should help to establish rules to predict the folding pattern and
      stability of G-quadruplexes.

PMID- 30184169
TI  - Measles cases hit record high in Europe in 2018.

PMID- 30184170
TI  - Where are we now with kidney disease in the human immunodeficiency virus-infected
      individual?

PMID- 30184168
TI  - Relationship of food insecurity to women's dietary outcomes: a systematic review.
AB  - Context: Food insecurity matters for women's nutrition and health. Objective:
      This review sought to comprehensively evaluate how food insecurity relates to a
      full range of dietary outcomes (food groups, total energy, macronutrients,
      micronutrients, and overall dietary quality) among adult women living in Canada
      and the United States. Data sources: Peer-reviewed databases (PubMed/MEDLINE,
      CINAHL, Scopus, Web of Science) and gray literature sources from 1995 to 2016
      were searched. Data extraction: Observational studies were used to calculate a
      percentage difference in dietary intake for food-insecure and food-secure groups.
      Results: Of the 24 included studies, the majority found food-insecure women had
      lower food group frequencies (dairy, total fruits and vegetables, total grains,
      and meats/meat alternatives) and intakes of macro- and micronutrients relative to
      food-secure women. Methodological quality varied. Among high-quality studies,
      food insecurity was negatively associated with dairy, fruits and vegetables,
      grains, meats/meats alternatives, protein, total fat, calcium, iron, magnesium,
      vitamins A and C, and folate. Conclusions: Results hold practical relevance for
      selecting nutritional targets in programs, particularly for nutrient-rich foods
      with iron and folate, which are more important for women's health.

PMID- 30184171
TI  - HiCDB: a sensitive and robust method for detecting contact domain boundaries.
AB  - Contact domains are closely linked to gene regulation and lineage commitment,
      while current understanding of contact domains and their boundaries is still
      limited. Here, we present a novel method HiCDB, which is constructively based on
      local relative insulation metric and multi-scale aggregation approach to detect
      contact domain boundaries (CDBs) on Hi-C maps. Compared with other 'state-of-art'
      methods, HiCDB shows improved sensitivity and specificity in determining CDBs at
      various Hi-C resolutions. The superiority of HiCDB enabled us to study the
      epigenetic features of detected CDBs and showed enrichment of architectural
      proteins and cell-type-specific transcription factor binding sites at CDBs. The
      further comparison of GM12878 and IMR90 Hi-C datasets suggested that cell-type
      specific CDBs are marked by active regulatory signals and correlate with
      activation of nearby cell identity genes.

PMID- 30184172
TI  - The association of interdialytic blood pressure variability with cardiovascular
      events and all-cause mortality in haemodialysis patients.
AB  - Background: Long-term pre-dialysis blood pressure variability (BPV) in
      haemodialysis patients is associated with increased cardiovascular risk. The
      association of the main haemodynamic culprit in dialysis, that is, short-term
      BPV, with outcomes has not been investigated. We examine the prognostic role of
      short-term BPV for mortality and cardiovascular events in this population.
      Methods: A total of 227 haemodialysis patients underwent 44-h ambulatory
      monitoring during a standard interval and were followed-up for 30.17 +/- 17.70
      months. We calculated SD, weighted SD (wSD), coefficient of variation (CV) and
      average real variability (ARV) of BP with validated formulas. The primary
      endpoint was first occurrence of all-cause death, non-fatal myocardial infarction
      or non-fatal stroke. Secondary endpoints were: (i) all-cause mortality, (ii)
      cardiovascular mortality and (iii) a combination of cardiovascular events.
      Results: Cumulative freedom from the primary endpoint was similar for quartiles
      of pre-dialysis and 44-h systolic BP (SBP), but was progressively longer for
      increasing quartiles of 44-h SBP-SD (P = 0.014), wSD (P = 0.007), CV (P = 0.031)
      and ARV (83.9, 71.9, 70.2 and 43.9% for quartiles 1-4; P < 0.001). Higher
      quartiles of 44-h SBP-ARV were associated with higher risk of all studied
      outcomes. Among diastolic BPV indices, 44-h diastolic BP (DBP)-CV and 44-h DBP
      ARV were associated with increased risk for the composite cardiovascular outcome.
      In Cox regression analysis, SBP-BPV was related to the primary endpoint,
      independently of SBP levels and interdialytic weight gain [ARV: hazard ratio (HR)
      1.115, 95% confidence interval (95% CI) 1.048-1.185]. This association become
      insignificant after adjustment for pulse wave velocity (PWV; HR 1.061, 95% CI
      0.989-1.137), and further attenuated after additional adjustment for age,
      dialysis vintage, gender, comorbidities and prevalent cardiovascular disease (HR
      1.031, 95% CI 0.946-1.122). Conclusions: Increased BPV during the interdialytic
      interval is associated with higher risk of death and cardiovascular events,
      whereas ambulatory BP levels are not. This association was not independent after
      adjustment for PWV, other risk factors and prevalent cardiovascular disease.
      Short-term BPV could be a mediator promoting the adverse cardiovascular profile
      of haemodialysis patients.

PMID- 30184173
TI  - New diagnostic tools for yellow fever.

PMID- 30184174
TI  - Telmisartan and thiorphan combination treatment attenuates fibrosis and apoptosis
      in preventing diabetic cardiomyopathy.
AB  - Aims: LCZ696, a first-generation dual angiotensin receptor-neprilysin inhibitor
      (ARNi), is effective in treating heart failure patients. However, the role of
      ARNis in treating diabetic cardiomyopathy is poorly understood. This study
      evaluates the efficacy of a novel combination of telmisartan [angiotensin
      receptor blocker (ARB)] and thiorphan [neprilysin inhibitor (NEPi)] in
      ameliorating diabetic cardiomyopathy while, at the same time, exploring the
      relevant underlying molecular mechanism(s). Methods and Results: Diabetes was
      induced by administration of streptozotocin (55mg/kg, i.p.) in male Wistar rats.
      After four weeks, diabetic rats were subjected to either thiorphan (0.1
      mg/kg/day, p.o.) or telmisartan (10 mg/kg/day, p.o.) monotherapy, or their
      combination, for a period of four weeks. Metabolic and morphometric alterations,
      failing ventricular functions and diminished baroreflex indicated development of
      diabetic cardiac complications. Apart from morphometric alterations, all
      pathological consequences were prevented by telmisartan and thiorphan combination
      therapy. Diabetic rats exhibited significant modulation of the natriuretic
      peptide system, a key haemodynamic regulator; this was normalised by combination
      therapy. Histopathological studies showed augmented myocardial fibrosis,
      demonstrated by increased % PSR positive area, with combination therapy giving
      the best improvement in these indices. More importantly, the combination of
      thiorphan and telmisartan was superior in attenuating inflammatory (NF-kappaB/MCP
      1), pro-fibrotic (TGF-beta/Smad7) and apoptotic (PARP/Caspase-3) cascades
      compared to respective monotherapies when treating rats with diabetic
      cardiomyopathy. In addition, diabetic heart chromatin was in a state of active
      transcription, indicated by increased histone acetylation (H2AK5Ac, H2BK5Ac,
      H3K9Ac and H4K8Ac) and histone acetyltransferase (PCAF and Ac-CBP) levels.
      Interestingly, combination treatment was sufficiently potent to normalise these
      alterations. Conclusion: The protective effect of novel ARB and NEPi combination
      against diabetic cardiomyopathy can be attributed to inhibition of inflammatory,
      pro-fibrotic and apoptotic cascades. Moreover, reversal of histone acetylation
      assists its protective effect.

PMID- 30184175
TI  - Comparative genomics of Czech vaccine strains of Bordetella pertussis.
AB  - Bordetella pertussis is a strictly human pathogen causing the respiratory
      infectious disease called whooping cough or pertussis. B. pertussis adaptation to
      acellular pertussis vaccine pressure has been repeatedly highlighted, but recent
      data indicate that adaptation of circulating strains started already in the era
      of the whole cell pertussis vaccine (wP) use. We sequenced the genomes of five B.
      pertussis wP vaccine strains isolated in the former Czechoslovakia in the pre-wP
      (1954-1957) and early wP (1958-1965) eras, when only limited population travel
      into and out of the country was possible. Four isolates exhibit a similar genome
      organization and form a distinct phylogenetic cluster with a geographic
      signature. The fifth strain is rather distinct, both in genome organization and
      SNP-based phylogeny. Surprisingly, despite isolation of this strain before 1966,
      its closest sequenced relative appears to be a recent isolate from the US. On the
      genome content level, the five vaccine strains contained both new and already
      described regions of difference. One of the new regions contains duplicated genes
      potentially associated with transport across the membrane. The prevalence of this
      region in recent isolates indicates that its spread might be associated with
      selective advantage leading to increased strain fitness.

PMID- 30184176
TI  - Twenty years of bioinformatics research for protease-specific substrate and
      cleavage site prediction: a comprehensive revisit and benchmarking of existing
      methods.
AB  - The roles of proteolytic cleavage have been intensively investigated and
      discussed during the past two decades. This irreversible chemical process has
      been frequently reported to influence a number of crucial biological processes
      (BPs), such as cell cycle, protein regulation and inflammation. A number of
      advanced studies have been published aiming at deciphering the mechanisms of
      proteolytic cleavage. Given its significance and the large number of functionally
      enriched substrates targeted by specific proteases, many computational approaches
      have been established for accurate prediction of protease-specific substrates and
      their cleavage sites. Consequently, there is an urgent need to systematically
      assess the state-of-the-art computational approaches for protease-specific
      cleavage site prediction to further advance the existing methodologies and to
      improve the prediction performance. With this goal in mind, in this article, we
      carefully evaluated a total of 19 computational methods (including 8 scoring
      function-based methods and 11 machine learning-based methods) in terms of their
      underlying algorithm, calculated features, performance evaluation and software
      usability. Then, extensive independent tests were performed to assess the
      robustness and scalability of the reviewed methods using our carefully prepared
      independent test data sets with 3641 cleavage sites (specific to 10 proteases).
      The comparative experimental results demonstrate that PROSPERous is the most
      accurate generic method for predicting eight protease-specific cleavage sites,
      while GPS-CCD and LabCaS outperformed other predictors for calpain-specific
      cleavage sites. Based on our review, we then outlined some potential ways to
      improve the prediction performance and ease the computational burden by applying
      ensemble learning, deep learning, positive unlabeled learning and parallel and
      distributed computing techniques. We anticipate that our study will serve as a
      practical and useful guide for interested readers to further advance next
      generation bioinformatics tools for protease-specific cleavage site prediction.

PMID- 30184177
TI  - Chlorothalonil biotransformation by cytochrome P450 monooxygenases in Sclerotinia
      homoeocarpa.
AB  - Cytochrome P450s have been shown to play a vital role in the xenobiotic
      detoxification system of Sclerotinia homoeocarpa, the causal agent of the
      turfgrass disease dollar spot. A previous study indicated that three CYP450s were
      validated to play a functional role in resistance against different fungicide
      classes including propiconazole and plant growth regulator, flurprimidol. In this
      study, we present these CYP450s possess the capability to modify the multi-site
      mode of action fungicide chlorothalonil. Chlorothalonil is an extensively used
      contact fungicide and has been shown to persist in soils. High Performance Liquid
      Chromatography (HPLC) indicated faster rates of chlorothalonil biotransformation
      by CYP561 and CYP65 overexpression strains when compared to the wild-type and
      CYP68 overexpression strain. Our GC-MS results show that the primary
      transformation intermediate found in soils, 4-hydroxy-2,5,6 trichloro
      isophthalonitrile is produced by CYP450s' metabolism. These findings suggest
      fungal CYP450s can biotransform chlorothalonil for biodegradation or
      detoxification.

PMID- 30184178
TI  - Clinical and Epidemiologic Patterns of Chikungunya Virus Infection and Coincident
      Arboviral Disease in a School Cohort in Haiti, 2014-2015.
AB  - Background: Beginning in December 2013, an epidemic of chikungunya virus (CHIKV)
      infection spread across the Caribbean and into virtually all countries in the
      Western hemisphere, with >2.4 million cases reported through the end of 2017.
      Methods: We monitored a cohort of school children in rural Haiti from May 2014,
      through February 2015, for occurrence of acute undifferentiated febrile illness,
      with clinical and laboratory data available for 252 illness episodes. Results:
      Our findings document passage of the major CHIKV epidemic between May and July
      2014, with 82 laboratory-confirmed cases. Subsequent peaks of febrile illness
      were found to incorporate smaller outbreaks of dengue virus serotypes 1 and 4 and
      Zika virus, with identification of additional infections with Mayaro virus,
      enterovirus D68, and coronavirus NL63. CHIKV and dengue virus serotype 1
      infections were more common in older children, with a complaint of arthralgia
      serving as a significant predictor for infection with CHIKV (odds ratio, 16.2;
      95% confidence interval, 8.0-34.4; positive predictive value, 66%; negative
      predictive value, 80%). Conclusions: Viral/arboviral infections were
      characterized by a pattern of recurrent outbreaks and case clusters, with the
      CHIKV epidemic representing just one of several arboviral agents moving through
      the population. Although clinical presentations of these agents are similar,
      arthralgias are highly suggestive of CHIKV infection.

PMID- 30184179
TI  - Large-Scale Structure and Individual Fingerprintsof Locally Coupled Sleep
      Oscillations.
AB  - Slow oscillations and sleep spindles, the canonical electrophysiological
      oscillations of non-rapid eye movement sleep, are thought to gate incoming
      sensory information, underlie processes of sleep-dependent memory consolidation,
      and are altered in various neuropsychiatric disorders. Accumulating evidence of
      the predominantly local expression of these individual oscillatory rhythms
      suggests that their cross-frequency interactions may have a similar local
      component. However, it is unclear whether locally coordinated sleep oscillations
      exist across the cortex, and whether and how these dynamics differ between fast
      and slow spindles, and sleep stages. Moreover, substantial individual variability
      in the expression of both spindles and slow oscillations raises the possibility
      that their temporal organization shows similar individual differences. Using two
      nights of multi-channel electroencephalography recordings from 24 healthy
      individuals, we characterized the topography of slow oscillation-spindle
      coupling. We found that while slow oscillations are highly restricted in spatial
      extent, the phase of the local slow oscillation modulates local spindle activity
      at virtually every cortical site. However, coupling dynamics varied with spindle
      class, sleep stage, and cortical region. Moreover, the slow oscillation phase at
      which spindles were maximally expressed differed markedly across individuals
      while remaining stable across nights. These findings both add an important
      spatial aspect to our understanding of the temporal coupling of sleep
      oscillations and demonstrate the heterogeneity of coupling dynamics, which must
      be taken into account when formulating mechanistic accounts of sleep-related
      memory processing.

PMID- 30184181
TI  - Safety and Efficacy of a Novel Vaginal Anti-infective, TOL-463, in the Treatment
      of Bacterial Vaginosis and Vulvovaginal Candidiasis: A Randomized, Single-blind,
      Phase 2, Controlled Trial.
AB  - Background: Bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC) present
      serious reproductive health risks and management challenges, with poor control
      attributed to survival of treatment-resistant biofilm communities. Boric acid is
      used in various regimens for non-albicans VVC and recurrent BV. We investigated
      safety and efficacy of a novel boric acid-based vaginal anti-infective with
      enhanced antibiofilm activity (TOL-463) in treating BV and VVC. Methods: In this
      phase 2 randomized, investigator-blinded trial conducted at 2 sexual health
      clinics, women with BV or VVC were randomly assigned (1:1) to 7 nights of TOL-463
      vaginal gel or insert. The primary test of cure (TOC) was clinical cure at day 9
      12; safety was assessed at TOC and day 21-30. Results: One hundred six
      participants (53 with BV, 36 VVC, 17 both) were enrolled; most were African
      American (69%). Clinical cure rate of BV at TOC was 59% (95% confidence interval
      [CI], 41%-75%) for TOL-463 insert and 50% (95% CI, 31%-69%) for TOL-463 gel, and
      for VVC, 92% (95% CI, 67%-99%) for TOL-463 insert and 81% (95% CI, 57%-93%) for
      TOL-463 gel. Both products were safe and well tolerated with no secondary cases
      of VVC; vulvovaginal burning was the most common adverse event (9.6%).
      Conclusions: TOL-463, especially in vaginal insert form, is effective and safe in
      treating BV and VVC. Future studies should assess the potential role of TOL-463
      as a biofilm disrupter in enhancing likelihood of cure relative to approved
      therapies, reducing recurrence rates, and combined with traditional
      antimicrobials. Clinical Trials Registration: NCT02866227.

PMID- 30184180
TI  - Global landscape of mouse and human cytokine transcriptional regulation.
AB  - Cytokines are cell-to-cell signaling proteins that play a central role in immune
      development, pathogen responses, and diseases. Cytokines are highly regulated at
      the transcriptional level by combinations of transcription factors (TFs) that
      recruit cofactors and the transcriptional machinery. Here, we mined through three
      decades of studies to generate a comprehensive database, CytReg, reporting 843
      and 647 interactions between TFs and cytokine genes, in human and mouse
      respectively. By integrating CytReg with other functional datasets, we determined
      general principles governing the transcriptional regulation of cytokine genes. In
      particular, we show a correlation between TF connectivity and immune phenotype
      and disease, we discuss the balance between tissue-specific and pathogen
      activated TFs regulating each cytokine gene, and cooperativity and plasticity in
      cytokine regulation. We also illustrate the use of our database as a blueprint to
      predict TF-disease associations and identify potential TF-cytokine regulatory
      axes in autoimmune diseases. Finally, we discuss research biases in cytokine
      regulation studies, and use CytReg to predict novel interactions based on co
      expression and motif analyses which we further validated experimentally. Overall,
      this resource provides a framework for the rational design of future cytokine
      gene regulation studies.

PMID- 30184183
TI  - Safety and immunogenicity of pneumococcal conjugate vaccines in a high-risk
      population: a randomised controlled trial of 10-valent and 13-valent PCV in Papua
      New Guinean infants.
AB  - Background: There are little data on the immunogenicity of PCV10 and PCV13 in the
      same high-risk population. Methods: PCV10 and PCV13 were studied head-to-head in
      a randomized controlled trial in Papua New Guinea in which 262 infants received
      three doses of PCV10 or PCV13 at 1, 2, and 3 months of age. Serotype-specific IgG
      concentrations, and pneumococcal and non-typeable Haemophilus influenzae (NTHi)
      carriage were assessed pre-vaccination, and at 4 and 9 months of age. Infants
      were followed for safety until 9 months of age. Results: One month after the
      third dose of PCV10 or PCV13, ?80% of infants had IgG concentrations >=0.35ug/mL
      for vaccine serotypes, and six months post-vaccination IgG concentrations
      >=0.35ug/mL were maintained for 8/10 shared PCV serotypes in ?75% of children
      vaccinated with either PCV10 or PCV13. . Children carried a total of 65 different
      pneumococcal serotypes (plus nonserotypeable). At 4 months of age, 92% (95%
      confidence interval (CI) 85-96) of children vaccinated with PCV10 and 81% (95% 72
      88) vaccinated with PCV13 were pneumococcal carriers (p = 0.023), while no
      differences were seen at 9 months of age, or for NTHi carriage. Both vaccines
      were well tolerated and not associated with serious adverse events. Conclusions:
      Infant vaccination with 3 doses of PCV10 or PCV13 is safe and immunogenic in a
      highly endemic setting; however, to significantly reduce pneumococcal disease in
      these settings, PCVs with broader serotype coverage and potency to reduce
      pneumococcal carriage are needed.

PMID- 30184182
TI  - Severe and complicated varicella and associated genotypes 10 years after
      introduction of a one dose varicella vaccine program.
AB  - Objectives: This national, sentinel prospective study aimed to identify children
      with severe hospitalized varicella despite availability of universal one-dose
      vaccination from 2005 and determine associations between virus genotypes and
      disease severity. Methods: Children with varicella or zoster from five Paediatric
      Active Enhanced Disease Surveillance hospitals were enrolled. Lesions were
      swabbed for genotyping. Associations with disease severity were analyzed using
      multiple regression. Results: From 2007-2015, 327 children with confirmed
      varicella (n=238) or zoster (n=89) were enrolled. 203 (62%) were immunocompetent
      children; including five of eight children who required intensive care unit
      management. 18% (36/203) of immunocompetent children had been previously
      vaccinated. Vaccinated children aged >18 months were less likely to have severe
      disease (9% (5/56)) than unvaccinated children (21% (21/100);p=0.05). Three of
      126 children who had virus genotyping (two immunocompromised) had varicella (n=2)
      or zoster (n=2) due to the Oka/vaccine strain. European origin clades
      predominated and were independently associated with more severe disease (OR 3.2
      (95%CI 1.1, 9.5);p=0.04). Conclusion: Severe hospitalized varicella still occurs
      with a one-dose varicella program, although predominantly in unvaccinated
      children. Most one-dose vaccine recipients were protected against severe disease.
      Viral genotyping in complex hospitalized cases is important to assist in
      monitoring disease due to Oka-vaccine strain.

PMID- 30184184
TI  - ROC75 Functions as an Attenuator of the Circadian Clock to Control
      Photoprotective LHCSR3 Gene in Chlamydomonas reinhardtii.
AB  - Strong light intensity leads to harmful overexcitation of the photosystems in
      green algae. In Chlamydomonas reinhardtii, LHCSR3 is required for the rapid
      protective response known as energy-dependent quenching (qE). Because the
      majority of photoacclimation analysis has been conducted under controlled
      laboratory conditions, physiological responses to natural environmental changes
      such as light/dark cycles have not been examined in detail. Regarding fitness in
      higher plants and microalgae, light-dark cycles represent a major Zeitgeber for
      synchronizing the circadian clock to multiple physiological responses, yet there
      is little consensus with respect to the clock response to high-intensity light in
      photosynthetic organisms. In a previous study, 105 circadian rhythm insertional
      mutants were isolated as rhythm of chloroplast (roc) mutants. Here, we report our
      characterization of the roc75 mutant, which exhibited a significantly higher qE
      value and LHCSR3 protein accumulation when grown under red light. We performed
      transcript analysis of ROC75 in the pcry (plant-cryptochrome) and phot mutants
      and found that only the former accumulated lower levels of ROC75 mRNA, suggesting
      that the blue light photoreceptor pCRY positively regulates ROC75. However, the
      degradation of pCRY by high-light exposure contributes to prevent over
      accumulation of ROC75, which in turn facilitates the PHOT mediated main
      activation pathway for LHCSR3. Furthermore, LHCSR3 mRNA exhibited a circadian
      rhythm, though its basal expression level in the roc75 mutant was higher than
      that in WT. We therefore conclude that ROC75 acts as an attenuator of the
      circadian clock to control LHCSR3 expression with blue and red light as stimuli
      for attenuation.

PMID- 30184185
TI  - Identifying "real-world" initiatives for knowledge translation tools: a case
      study of community-based physical activity programs for persons with physical
      disability in Canada.
AB  - "Real-world" initiatives represent an important source of information for
      evidence-based practice; however, accessing information about initiatives is
      often challenging. Casebooks are an innovative knowledge translation (KT) tool
      for researchers, practitioners, and end-users to address "research-to
      implementation gaps" through sharing "real-world" experiences. Several casebooks
      have been published; yet, they remain inconsistent in their methodological
      approach for identifying "real-world" initiatives. The purpose of this project is
      to describe and apply systematic scoping study methods for the identification of
      "real-world" initiatives relevant for the development of KT tools. Specifically,
      systematic scoping study methods were developed to identify community-based
      physical activity (PA) programs for persons with physical disabilities across
      Canada. To identify PA programs, a search strategy was developed and included
      five distinct search approaches: (i) peer-reviewed literature databases, (ii)
      grey literature databases, (iii) customized Google search engines, (iv) targeted
      websites, and (v) consultation with content experts. Title screening and hand
      searching identified 478 potentially relevant PA programs. Full record review
      identified 72 PA programs that met KT tool criteria. The most comprehensive
      search approach was targeted websites, which identified 25 (35%) unique PA
      programs, followed by content experts (n = 12; 17%). Only four (5.6%) unique PA
      programs were identified via custom Google searching. No PA programs were
      uniquely identified through peer- or grey literature database searches. This
      study describes and applies a systematic scoping study methodology that serves as
      a basis for identifying and selecting "real-world" initiatives that are central
      to the development of evidence-based KT tools.

PMID- 30184186
TI  - Expanding home-based management of malaria to all age groups in Rwanda: analysis
      of acceptability and facility-level time-series data.
AB  - Background: In response to a resurgence of malaria in Rwanda, home-based
      management (HBM) was expanded to enable community-health workers (CHWs) to
      provide malaria treatment to patients of all ages. We assessed the effect of the
      expanded HBM program on malaria case presentations at health facilities. Methods:
      Services provided by CHWs and health facility presentations among individuals >5
      y of age were considered. Presentations to CHWs were analyzed descriptively to
      assess acceptability and segmented regression modeling using facility-level data
      was employed to compare changes between the pre- and postintervention periods for
      intervention and control districts. Results: Individuals >5 y of age readily
      accessed malaria diagnosis and treatment services from CHWs. Severe and
      uncomplicated malaria increased in the postintervention period for both the
      intervention and control districts. Presentations for uncomplicated malaria
      increased in the intervention and control districts to a similar degree. Severe
      cases increased to a greater degree in the intervention districts immediately
      after HBM was expanded compared with controls, but the monthly rate of increase
      was lower in the intervention districts. Conclusions: Services were shifted to
      CHWs, as demonstrated by the number of individuals treated through the expanded
      program. The rate of severe malaria increased immediately after implementation
      within intervention districts relative to controls, potentially because of
      enhanced case-finding. The rate of increase in severe cases was lower in the
      intervention districts comparatively, likely due to expedited treatment.

PMID- 30184187
TI  - Lateralized Rhythmic Acoustic Stimulation during Daytime NREM Sleep Enhance Slow
      Waves.
AB  - Slow wave sleep (SWS) is characterized by the predominance of delta waves and
      slow oscillations, reflecting the synchronized activity of large cortical
      neuronal populations. Amongst other functions, SWS plays a crucial role in the
      restorative capacity of sleep. Rhythmic Acoustic Stimulation (RAS) during SWS has
      been shown a cost-effective method to enhance slow wave activity. Slow wave
      activity can be expressed in a region-specific manner as a function of previous
      waking activity. However, it is unclear whether slow waves can be enhanced in a
      region-specific manner using RAS. We investigated the effects of unilaterally
      presented rhythmic acoustic sound patterns on sleep EEG oscillations. Thirty-five
      participants received during SWS 12-seconds long rhythmic bursts of pink noise
      (at a rate of 1 Hz) that alternated with non-stimulated, silent periods,
      unilaterally delivered into one of the ears of the participants. As expected, RAS
      enhanced delta power, especially in its low frequency components between 0.75 and
      2.25 Hz. However, increased slow oscillatory activity was apparent in both
      hemispheres regardless of the side of the stimulation. The most robust increases
      in slow oscillatory activity appeared during the first 3-4 seconds of the
      stimulation period. Furthermore, a short-lasting increase in theta and sigma
      power was evidenced immediately after the first pulse of the stimulation
      sequences. Our findings indicate that lateralized RAS has a strong potential to
      globally enhance slow waves during daytime naps. The lack of localized effects
      suggests that slow waves are triggered by the ascending reticular system and not
      directly by specific auditory pathways.

PMID- 30184188
TI  - Age-Related Upper Limits in Physical Performances.
AB  - Maximal physical performances are powerful and accurate biomarkers in the
      understanding of age-related changes during the aging process. Previous studies
      have characterized age-related changes from Caenorhabditis elegans to Homo
      sapiens. We characterized changes in this pattern for H. sapiens, decade by
      decade, from 1970 to 2017. Using 286,916 performances related to age from the
      world's best performances in each age group, we measured the relative change of
      10 different running and jumping events for both women and men. We compared the
      change in sexual dimorphism with age and showed that the gender gap in maximal
      performance regarding age increases gradually, especially after the age of 50.
      Between 1970 and 2017, the performances for all age groups in all events have
      slightly progressed. However, during the last decades, the relative progression
      of the best performances for all age groups has decreased in both range and
      frequency, suggesting that age-related maximal physical performances for H.
      sapiens are reaching their physiological limits.

PMID- 30184189
TI  - The two-component regulatory system CpxA/R is required for the pathogenesis of
      Aeromonas hydrophila.
AB  - Aeromonas hydrophila is a causative pathogen of many infectious diseases in fish
      and human. The two-component regulatory system enables bacteria to respond to a
      wide range of stimuli, growth conditions and environments. The two-component
      system CpxA/R is prevalent in microorganisms and involved in the pathogenesis of
      a number of pathogens. In this study, we generated a DeltacpxA/R mutant of A.
      hydrophila ZYAH72 to explore the biological functions mediated by the CpxA/R in
      this organism. Compared with the wild type strain, the knockout mutant strain
      DeltacpxA/R exhibited a significant impairment in adherence to human epithelial
      cells Caco-2 and resistance against host killing in fish blood. However, the
      mutant strain and the wild type strain showed no difference in the cytotoxicity
      assay, which revealed that the absence of CpxA/R did not influence the cytopathic
      effect of this pathogen in vitro. Furthermore, the virulence of DeltacpxA/R was
      attenuated in zebrafish (Danio rerio) and grass carp (Ctenopharyngodon idella)
      infections, with reduced mortality or delayed death time. These findings suggest
      that CpxA/R is required for the virulence of A. hydrophila.

PMID- 30184190
TI  - The Three Members of the Arabidopsis thaliana Glycosyltransferase Family 92 are
      Functional beta-1,4-Galactan Synthases.
AB  - Pectin is a major component of primary cell walls and performs a plethora of
      functions crucial for plant growth, development and plant-defense responses.
      Despite the importance of pectic polysaccharides their biosynthesis is poorly
      understood. Several genes have been implicated in pectin biosynthesis by mutant
      analysis, but biochemical activity has been shown for very few.We used reverse
      genetics and biochemical analysis to study members of Glycosyltransferase Family
      92 (GT92) in Arabidopsis thaliana. Biochemical analysis gave detailed insight
      into the properties of GALS1 (Galactan synthase 1) and showed galactan synthase
      activity of GALS2 and GALS3. All proteins are responsible for adding galactose
      onto existing galactose residues attached to the rhamnogalacturonan-I (RG-I)
      backbone. Significant GALS activity was observed with galactopentaose as acceptor
      but longer acceptors are favored. Overexpression of the GALS proteins in
      Arabidopsis resulted in accumulation of unbranched beta-1,4-galactan. Plants in
      which all three genes were inactivated had no detectable beta-1,4-galactan, and
      surprisingly these plants exhibited no obvious developmental phenotypes under
      standard growth conditions. RG-I in the triple mutants retained branching
      indicating that the initial Gal substitutions on the RG-I backbone are added by
      enzymes different from GALS.

PMID- 30184191
TI  - Responses to competition for nitrogen between subtropical native tree seedlings
      and exotic grasses are species-specific and mediated by soil N availability.
AB  - Competitive interactions between native tree seedlings and exotic grasses
      frequently hinder forest restoration. We investigated the consequences of
      competition with exotic grasses on the growth and net nitrogen (N) uptake
      capacity of native rainforest seedlings used for reforestation depending on soil
      N availability and N source. Tree seedlings and grasses were grown in the
      greenhouse in different competition regimes (one tree species vs one grass
      species) and controls (grass monocultures or single tree seedlings) at low and
      high soil N. After 8 weeks, we quantified net N uptake capacity using 15N
      labelled organic (i.e., glutamine and arginine) and inorganic (i.e., ammonium and
      nitrate) N sources and biomass indices. Depending on soil N availability, we
      observed different species-specific responses to growth and N acquisition. Tree
      seedlings generally increased their net N uptake capacity in response to
      competition with grasses, although overall seedling growth was unaffected. In
      contrast, the responses to competition by the grasses were species-specific and
      varied with soil N availability. The different N acquisition strategies suggest
      the avoidance of competition for N between trees and grasses. Overall, the
      results highlight that quantifying underlying mechanisms of N acquisition
      complements the information on biomass allocation as a measure of responses to
      competition, particularly with varying environmental conditions.

PMID- 30184192
TI  - Age-related Decline in Learning Deterministic Judgment-Based Sequences.
AB  - Objectives: Because sequence learning is integral to cognitive functions across
      the lifespan, the present study examined the effect of healthy aging on
      deterministic judgment-based sequence learning. Methods: College-aged, younger
      old, and older-old adults completed a judgment-based sequence learning task which
      required them to learn a full sequence by chaining together single stimulus
      response associations in a step-by-step fashion. Results: Results showed that
      younger adults outperformed younger-old and older-old adults; older adults were
      less able to acquire the full sequence and committed significantly more errors
      during learning. Additionally, higher sequence learning errors was associated
      with advancing age among older adults, even when controlling for other factors
      known to contribute to sequence learning abilities. Such impairments were
      selective to learning sequential information, since adults of all ages performed
      equivalently on post-learning probe trials, as well as on learning simple
      stimulus-response associations. Discussion: This pattern of age deficits during
      deterministic sequence learning challenges past reports of age preservation.
      Though the neural processes underlying learning cannot be determined here, our
      patterns of age deficits and preservation may reflect different brain regions
      that are involved in the task phases, adding behavioral evidence to the emerging
      hypothesis of frontostriatal declines despite spared hippocampal function with
      age.

PMID- 30184193
TI  - Non-communicable diseases: ditch the label and recapture public awareness.
AB  - Non-communicable diseases (NCDs) are branded as the leading cause of global
      mortality. Global health thinking has dichotomised NCDs from communicable
      diseases to attract funding and end a dangerous neglect. However, NCDs can also
      have infectious disease risk factors, and mortality from NCDs is greatest in low-
      and middle-income countries, which face a syndemic burden of disease. As a non
      term, attention is not immediately focused around key 'human-made' risk factors
      for chronic disease. By continuing to use this flawed and ambiguous label,
      policymakers risk enforcing an ideological approach, which fails to encourage
      global health researchers to work collaboratively and to capture the political
      and public awareness required to motivate sustainable change.

PMID- 30184195
TI  - A probabilistic automated tagger to identify human-related publications.
AB  - The Medical Subject Heading 'Humans' is manually curated and indicates human
      related studies within MEDLINE. However, newly published MEDLINE articles may
      take months to be indexed and non-MEDLINE articles lack consistent, transparent
      indexing of this feature. Therefore, for up to date and broad literature
      searches, there is a need for an independent automated system to identify whether
      a given publication is human-related, particularly when they lack Medical Subject
      Headings. One million MEDLINE records published in 1987-2014 were randomly
      selected. Text-based features from the title, abstract, author name and journal
      fields were extracted. A linear support vector machine was trained to estimate
      the probability that a given article should be indexed as Humans and was
      evaluated on records from 2015 to 2016. Overall accuracy was high: area under the
      receiver operating curve = 0.976, F1 = 95% relative to MeSH indexing. Manual
      review of cases of extreme disagreement with MEDLINE showed 73.5% agreement with
      the automated prediction. We have tagged all articles indexed in PubMed with
      predictive scores and have made the information publicly available at
      http://arrowsmith.psych.uic.edu/evidence_based_medicine/index.html. We have also
      made available a web-based interface to allow users to obtain predictive scores
      for non-MEDLINE articles. This will assist in the triage of clinical evidence for
      writing systematic reviews.

PMID- 30184194
TI  - SAGE: a comprehensive resource of genetic variants integrating South Asian whole
      genomes and exomes.
AB  - South Asia is home to $?sim $20% of the world population and characterized by
      distinct ethnic, linguistic, cultural and genetic lineages. Only limited
      representative samples from the region have found its place in large population
      scale international genome projects. The recent availability of genome scale data
      from multiple populations and datasets from South Asian countries in public
      domain motivated us to integrate the data into a comprehensive resource. In the
      present study, we have integrated a total of six datasets encompassing 1213 human
      exomes and genomes to create a compendium of 154 814 557 genetic variants and
      adding a total of 69 059 255 novel variants. The variants were systematically
      annotated using public resources and along with the allele frequencies are
      available as a browsable-online resource South Asian genomes and exomes. As a
      proof of principle application of the data and resource for genetic epidemiology,
      we have analyzed the pathogenic genetic variants causing retinitis pigmentosa.
      Our analysis reveals the genetic landscape of the disease and suggests subset of
      genetic variants to be highly prevalent in South Asia.

PMID- 30184196
TI  - Enhancing acid tolerance of the probiotic bacterium Lactobacillus acidophilus
      NCFM with trehalose.
AB  - Enhancing the acid tolerance of the probiotic bacterial strain Lactobacillus
      acidophilus NCFM (L. acidophilus NCFM) is critical for improving its viability
      during transiting through gastrointestinal tract, which is the basis of eliciting
      beneficial effects as an intestinal probiotic. In this study, the role of
      trehalose and the glutamategamma-aminobutyric acid antiporter gene gadC in
      enhancing the acid tolerance of L. acidophilus NCFM was investigated. Trehalose
      at a concentration of 0.5% (w/v) was sufficient to significantly increase
      bacterial viability at pH 2.0, and trehalose of 2.0% can preserve more than 80%
      of bacterial viability both at pH 2.0 and 3.0. The inactivation of gadC gene in
      L. acidophilus NCFM significantly reduced bacterial viability at pH 2.0, and
      diminished the protective effect of trehalose against acid stress. In conclusion,
      exogeneous trehalose conferred L. acidophilus NCFM enhanced viability at extreme
      low pH values, an effect that appeared to depend on its endogenous glutamate
      depenent acid resistance system.

PMID- 30184198
TI  - Molecular variability and genetic structure of white spot syndrome virus strains
      from northwest Mexico based on the analysis of genomes.
AB  - White spot syndrome virus (WSSV) has a ~300 kb double-stranded DNA genome. It
      originated in China, spread rapidly through shrimp farms in Asia, and
      subsequently to America. This study determined complete genome sequences for nine
      historic WSSV strains isolated from Pacific white shrimp (Litopenaeus vannamei)
      captured in farm ponds in northwest Mexico (Sinaloa and Nayarit). Genomic DNA was
      captured by an amplification method using overlapping long-range PCR and
      sequencing by Ion Torrent-PGM. Complete genome sequences were assembled (length
      range 255-290 kb) and comparative genome analysis with WSSV strains revealed
      substantial deletions (3 and 10 kb in two regions) in seven strains, with two
      strains differing from the rest. Phylogenetic analysis identified that the WSSV
      strains from the northern area of the state of Sinaloa clustered with strains
      from China (LC1, LC10, DVI) and Korea (ACF2, ACF4), while those from the southern
      region of the state of Nayarit (AC1 and JP) differed from both of those and from
      strains found in Taiwan and Thailand. Our data offer insights into the diversity
      of the WSSV genome in one country and their divergent origin, suggest that it
      entered Mexico via multiple routes and that specific genome regions can
      accommodate substantial deletions without compromising viability.

PMID- 30184197
TI  - Burden for Parents of Patients With Schizophrenia-A Nationwide Comparative Study
      of Parents of Offspring With Rheumatoid Arthritis, Multiple Sclerosis, Epilepsy,
      and Healthy Controls.
AB  - Background: The study aimed to (1) compare the risk of health care use, adverse
      health status, and work productivity loss of parents of patients with
      schizophrenia to parents of patients with multiple sclerosis (MS), rheumatoid
      arthritis (RA), epilepsy, and healthy controls; and (2) evaluate such outcome
      measures while considering disease severity of schizophrenia. Methods: Based on
      linkage of Swedish registers, at least one parent was included (n = 18215) of
      patients with schizophrenia (information 2006-2013, n = 10883). Similarly,
      parental information was linked to patients with MS, RA, epilepsy, and matched
      healthy controls, comprising 11292, 15516, 34715, and 18408 parents,
      respectively. Disease severity of schizophrenia was analyzed. Different
      regression models yielding odds ratios (OR), hazard ratios (HR), or relative
      risks (RR) with 95% confidence intervals (CI) were run. Results: Psychiatric
      health care use, mainly due to anxiety and affective disorders, showed a strongly
      increasing trend for parents of patients with schizophrenia throughout the
      observation period. During the follow-up, these parents had an up to 2.7 times
      higher risk of specialized psychiatric health care and receipt of social welfare
      benefits than other parents. Parents of the moderately severely ill patients with
      schizophrenia had higher risk estimates for psychiatric health care (RR: 1.12;
      95% CI: 1.07-1.17) compared with parents of least severely ill patients.
      Conclusions: Parents of patients with schizophrenia have a considerably higher
      risk of psychiatric health care and social welfare benefit receipt than other
      parents. Psychiatric health care use worsens over time and with increasing
      disease severity of the offspring.

PMID- 30184199
TI  - Analysis and characterization of coenzyme B12 biosynthetic gene clusters and
      improvement of B12 biosynthesis in Pseudomonas denitrificans ATCC 13867.
AB  - Coenzyme B12 is an essential cofactor for many enzymes such as glycerol
      dehydratase, methionine synthase and methylmalonyl-CoA mutase. Herein, we
      revisited the B12 biosynthetic gene clusters (I and II) in Pseudomonas
      denitrificans, a well-known industrial producer of the coenzyme B12, to
      understand the regulation of gene expression and improve the production of
      coenzyme B12. There were eight operons, seven in cluster I and one in cluster II,
      and four operons were regulated by B12-responsive riboswitches with a switch-off
      concentration at ~5 nM coenzyme B12. DNA sequences of the four riboswitches were
      partially removed, individually or in combination, to destroy the structures of
      riboswitches, but no improvement was observed. However, when the whole length of
      riboswitches in cluster I were completely removed and promoters regulated by the
      riboswitches were replaced with strong constitutive ones, B12 biosynthesis was
      improved by up to 2-fold. Interestingly, modification of the promoter region for
      cluster II, where many (>10) late genes of B12 biosynthesis belong, always
      resulted in a significant, greater than 6-fold reduction in B12 biosynthesis.

PMID- 30184201
TI  - Selection of Bradyrhizobium or Ensifer symbionts by the native Indian
      caesalpinioid legume Chamaecrista pumila depends on soil pH and other edaphic and
      climatic factors.
AB  - Nodules of Chamaecrista pumila growing in several locations in India were sampled
      for anatomical studies and for characterization of their rhizobial
      microsymbionts. Regardless of their region of origin, the nodules were
      indeterminate with their bacteroids contained within symbiosomes which were
      surrounded by pectin. More than 150 strains were isolated from alkaline soils
      from the Thar Desert (Rajasthan), wet-acidic soils of Shillong (Meghalaya), and
      from trap experiments using soils from four other states with different agro
      ecological regions. Molecular phylogenetic analysis based on five housekeeping
      (rrs, recA, glnII, dnaK andatpD) and two symbiotic (nodA and nifH) genes was
      performed for selected strains. Chamaecrista pumila was shown to be nodulated by
      niche-specific diverse strains of either Ensifer or Bradyrhizobium in alkaline
      (Thar Desert) to neutral (Tamil Nadu) soils and only Bradyrhizobium strains in
      acidic (Shillong) soils. Concatenated core gene phylogenies showed four novel
      Ensifer-MLSA types and nine Bradyrhizobium-MLSA types. Genetically diverse
      Ensifer strains harbored similar sym genes which were novel. In contrast,
      significant symbiotic diversity was observed in the Bradyrhizobium strains. The
      C. pumila strains cross-nodulated Vigna radiata and some wild papilionoid and
      mimosoid legumes. It is suggested that soil pH and moisture level played
      important roles in structuring the C. pumila microsymbiont community.

PMID- 30184200
TI  - Sequence preference and structural heterogeneity of BZ junctions.
AB  - BZ junctions, which connect B-DNA to Z-DNA, are necessary for local
      transformation of B-DNA to Z-DNA in the genome. However, the limited information
      on the junction-forming sequences and junction structures has led to a lack of
      understanding of the structural diversity and sequence preferences of BZ
      junctions. We determined three crystal structures of BZ junctions with diverse
      sequences followed by spectroscopic validation of DNA conformation. The
      structural features of the BZ junctions were well conserved regardless of
      sequences via the continuous base stacking through B-to-Z DNA with A-T base
      extrusion. However, the sequence-dependent structural heterogeneity of the
      junctions was also observed in base step parameters that are correlated with
      steric constraints imposed during Z-DNA formation. Further, circular dichroism
      and fluorescence-based analysis of BZ junctions revealed that a base extrusion
      was only found at the A-T base pair present next to a stable dinucleotide Z-DNA
      unit. Our findings suggest that Z-DNA formation in the genome is influenced by
      the sequence preference for BZ junctions.

PMID- 30184202
TI  - Should travel medicine practitioners prescribe antibiotics for self-treatment of
      travelers' diarrhea?

PMID- 30184203
TI  - Addressing the gender-knowledge gap in glucose-6-phosphate dehydrogenase
      deficiency: challenges and opportunities.
AB  - Glucose-6-phosphate dehyrdgoenase (G6PD) deficiency is a common X-linked genetic
      trait, with an associated enzyme phenotype, whereby males are either G6PD
      deficient or normal, but females exhibit a broader range of G6PD deficiencies,
      ranging from severe deficiency to normal. Heterozygous females typically have
      intermediate G6PD activity. G6PD deficiency has implications for the safe
      treatment for Plasmodium vivax malaria. Individuals with this deficiency are at
      greater risk of serious adverse events following treatment with the only curative
      class of anti-malarials, 8-aminoquinolines, such as primaquine. Quantitative
      diagnostic tests for G6PD deficiency are complex and require sophisticated
      laboratories. The commonly used qualitative tests, do not discriminate
      intermediate G6PD activities. This has resulted in poor understanding of the
      epidemiology of G6PD activity in females and its corresponding treatment
      ramifications. New simple-to-use quantitative tests, and a momentum to eliminate
      malaria, create an opportunity to address this knowledge gap. While this will
      require additional resources for clinical studies, adequate operational research,
      and appropriate pharmacovigilance, the health benefits from this investment go
      beyond the immediate intervention for which the G6PD status is first diagnosed.

PMID- 30184205
TI  - The Ideal Psychiatry-A Utopia?

PMID- 30184204
TI  - Sustainability of clinical pathway guided care in cardiac surgery ICU patients; 9
      years experience in over 7500 patients.
AB  - Objective: To determine trends over time regarding inclusion of post-operative
      cardiac surgery intensive care unit (ICU) patients in a clinical pathway (CP),
      and the association with clinical outcome. Design: Retrospective cohort study.
      Setting: ICU of an academic hospital. Participants: All cardiac surgery patients
      operated between 2007 and 2015. Measures and Results: A total of 7553 patients
      were operated. Three patient groups were identified: patients treated according
      to CP (n = 6567), patients excluded from the CP within the first 48 h (n = 633)
      and patients never included in CP (n = 353). Patients treated according to CP
      increased significantly over time from 74% to 95% and the median Log EuroSCORE
      (predicted mortality score) in this group increased significantly over time (P =
      0.016). In-hospital length of stay (LOS) decreased in all groups, but
      significantly in CP group (P < 0.001). Overall, the in-hospital, and 1-year
      mortality decreased from 1.5 to 1.1% and 3.7 to 2.9%, respectively (both P <
      0.05). Patients with a Log EuroSCORE >10 were more likely excluded from CP (P <
      0.001), but, if included in CP, these patients had a significantly shorter
      Intensive Care stay and in-hospital stay compared to excluded patients with a Log
      EuroSCORE >10 (both P < 0.001). Conclusions: The use of a CP for all post
      operative cardiac surgery patients in the ICU is sustainable. While more complex
      patients were treated according to the CP, clinical outcome improved in the CP
      group.

PMID- 30184207
TI  - Review of the pharmacokinetic properties of nitrofurantoin and nitroxoline.
AB  - Nitrofurantoin and nitroxoline are oral antibiotics for the treatment or
      prophylaxis of acute urinary tract infections. New interest in both these drugs
      is increasing because of the emergence of resistance to other antibiotics, but
      knowledge of their pharmacokinetics (PK) is lacking since they were developed
      before the advent of standardized research for drug approval. The aims of this
      review were to (i) summarize the PK data reported in the literature and (ii) to
      identify PK knowledge gaps. The current body of PK knowledge of both drugs
      appears to be poor and mainly based on old studies. Nitrofurantoin PK values were
      obtained from studies using many variables, e.g. formulations, crystal sizes and
      analytical methods, resulting in high interindividual variability in PK
      parameters and no uniform PK profile. Clinical experience and PK data for
      nitroxoline are even more limited since the drug is registered in only Germany
      and a few (Eastern European) countries. Clinical studies in relevant patient
      populations are needed with commercially available nitrofurantoin and nitroxoline
      formulations at approved dosing regimens to more fully characterize their PK
      profiles, and to investigate the influence of patient characteristics on these
      profiles in order to optimize efficacy and avoid toxicity and emergence of
      resistance. Only with this updated knowledge and efficacy data from well
      structured trials can both drugs maintain their antimicrobial activity against
      uropathogens.

PMID- 30184206
TI  - White matter endophenotypes and correlates for the clinical diagnosis of autism
      spectrum disorder.
AB  - Since prior diffusion tensor imaging (DTI) studies reported no significant
      differences in white matter organizations between individuals with autism
      spectrum disorder (ASD) and their unaffected siblings, the neural correlates for
      developing a clinical diagnosis among people with endophenotypes remain
      undetermined. We obtained DTI data from a total of 60 participants consisting of
      30 people with endophenotypes and 30 people without. We first followed a
      conventional approach by comparing individuals with ASD and their unaffected
      siblings. Using region-of-interest approach, we then performed bootstrapping to
      examine whether the differences in white matter organizations between individuals
      with ASD and their unaffected siblings were substantially large, considering the
      distribution of differences between typically developing (TD) siblings.
      Conventional approaches revealed no significant differences in white matter
      organizations between individuals with ASD and their unaffected siblings.
      Bootstrapping revealed a significantly large difference in axial diffusivity in
      the left stria terminalis between individuals with ASD and their unaffected
      siblings after accounting for the distribution of differences in axial
      diffusivity among TD siblings (99.998 percentile). The results remained
      significant after controlling for multiple comparisons with Bonferroni method. We
      assumed that one aspect of this tract was associated with the development of a
      clinical diagnosis.

PMID- 30184208
TI  - Effects of screening and universal healthcare on long-term colorectal cancer
      mortality.
AB  - Background: To evaluate the time trends of colorectal cancer (CRC) affected by a
      Nationwide Colorectal Cancer Screening (NCCS) programme with biennial faecal
      immunochemical testing (FIT) and Nationwide Healthcare Insurance (NHI). Methods:
      Data from the national registries on cancer and death in Taiwan were separated
      into years 1984-1993, 1994-2003 and 2004-2013 based on the implementations of NHI
      (starting 1995) and NCCS (starting 2004). The adult population was divided into
      three age groups (young, 30-49; middle-aged, 50-69; and old, 70-84 years); only
      the middle-aged were eligible for NCCS. Crude and adjusted effects of NCCS and
      NHI were quantified by percentage change and 95% confidence interval (CI) with
      respect to CRC mortality, according to the attributions from incidence and
      survival. Results: Within 335 million person-years of follow-up, 204 362 incident
      CRCs and 80 771 CRC-related deaths were identified. Increasing mortality trends
      were noted for 1994-2003 (post-NHI) vs 1984-1993 due to remarkable increasing
      incidence trends that could not be offset by improved survival as a result of
      NHI. During 2004-13 (post-NCCS), mortality continued to increase by 15% (95% CI:
      10-21%) in young adults (30-49 years) and 8% (95% CI: 6-11%) in older adults (70
      84 years), whereas middle-aged adults (50-69 years) had a reduction of 7% (95%
      CI: 5-9%) due to a remarkable stage shift and subsequent improvement in survival.
      In the middle-aged adults, increased incidence was less but survival improvement
      was more compared with other age groups. Conclusions: Whereas universal
      healthcare insurance led to improvement in CRC survival, FIT-based screening has
      made an even greater contribution to reducing CRC mortality.

PMID- 30184209
TI  - Objectively Measured Adherence in Adolescents With Type 1 Diabetes on Multiple
      Daily Injections and Insulin Pump Therapy.
AB  - Objectives: Type 1 diabetes (T1D) poses unique challenges to adherence-related
      behavior because of complex treatment regimens that vary by use of specific
      technologies. This study used objective data to determine (1) prevalence rates of
      adherence behaviors in adolescents with T1D, and (2) relationships between
      adherence and glycemic control. Methods: Data were downloaded for the past 30
      consecutive days from glucose meters and multiple insulin pump models for 80
      youth (11-17 years old; n = 40 on multiple daily injections (MDIs) and n = 40 on
      continuous subcutaneous insulin infusion [CSII]). Frequency of self-monitoring of
      blood glucose (SMBG; MDI and CSII users); carbohydrate entry (CSII users); daily
      insulin bolus delivery (CSII users); episodes of high, very high, and dangerously
      high hyperglycemia; and correction bolusing for hyperglycemia (CSII users) were
      calculated. Results: Participants completed SMBG >=4 times/day on 46.13% of days
      (MDI users), 48.74% of days (CSII users nonmanual entries only), and 59.07% of
      days (CSII users; manual plus nonmanual entries). CSII users entered
      carbohydrates >=3 times/day on 61.47% of days and bloused insulin >=3 times/ day
      on 87.34% of days. Hyperglycemic readings were followed by a correction bolus in
      <70% of cases. Greater SMBG, carbohydrate entry, bolus insulin delivery, and
      correction bolusing for high and very high hyperglycemia predicted lower glycated
      hemoglobin (sample M = 8.74%, SD = 1.75%). Conclusions: Objective data from
      diabetes technology are helpful to differentiate adherence to specific domains of
      treatment but are complex in nature. Findings support a need for further research
      to elucidate predictive factors of suboptimal adherence in adolescents with T1D.

PMID- 30184210
TI  - Intrafamilial Transmission of Parechovirus A and Enteroviruses in Neonates and
      Young Infants.
AB  - Background: Parechovirus A (PeV-A) is an important cause of sepsis and
      meningoencephalitis in neonates and young infants. Thus, identifying the source
      of PeV-A is essential for prevention; however, little is known regarding the
      spread of PeV-A among family members of PeV-A-infected neonates and young
      infants. Methods: In this prospective study, we evaluated stool samples from
      family members of PeV-A-infected neonates and infants younger than 4 months who
      presented with sepsis, meningoencephalitis, or both in Niigata, Japan, in 2016.
      Because of a simultaneous outbreak, enteroviruses (EVs) were also evaluated
      during this period. Real-time polymerase chain reaction followed by sequence
      analysis was used for viral diagnosis using serum and/or cerebrospinal fluid
      samples. Results: Among 54 febrile patients, the stool samples of 14 (26%) and 12
      (22%) patients tested positive for PeV-A and EV, respectively. Stool samples from
      54 family members (38 adults and 16 children) of 12 PeV-A-infected patients were
      available. The rate of PeV-A positivity in these samples was higher among the
      children (88% [14 of 16]) than the adults (34% [13 of 38]). Among family members
      with a PeV-A-positive stool sample, 29% (4 of 14) of the children and 77% (10 of
      13) of the adults were asymptomatic. Similarly, among 53 stool samples from
      family members (31 adults and 22 children) of 11 EV-infected patients, the rate
      of EV positivity in the stool samples was higher among the children (91% [20 of
      22]) than among the adults (42% [13 of 31]). The asymptomatic-patient rates were
      45% (9 of 20) among the children and 85% (11 of 13) among the adults in family
      members with EV-positive stool. Conclusions: Similar to EVs, PeV-A was detected
      frequently in stool samples from family members of PeV-A-infected patients. Among
      family members with PeV-A-positive stool, adults were more likely than children
      to be asymptomatic and therefore could be an important source of PeV-A infection.

PMID- 30184211
TI  - Painless Skin Ulcer in a 5-Year-Old Girl From Colombia.

PMID- 30184212
TI  - Rapid detection and discrimination of chromosome- and MCR-plasmid-mediated
      resistance to polymyxins by MALDI-TOF MS in Escherichia coli: the MALDIxin test.
AB  - Background: Polymyxins are currently considered a last-resort treatment for
      infections caused by MDR Gram-negative bacteria. Recently, the emergence of
      carbapenemase-producing Enterobacteriaceae has accelerated the use of polymyxins
      in the clinic, resulting in an increase in polymyxin-resistant bacteria.
      Polymyxin resistance arises through modification of lipid A, such as the addition
      of phosphoethanolamine (pETN). The underlying mechanisms involve numerous
      chromosome-encoded genes or, more worryingly, a plasmid-encoded pETN transferase
      named MCR. Currently, detection of polymyxin resistance is difficult and time
      consuming. Objectives: To develop a rapid diagnostic test that can identify
      polymyxin resistance and at the same time differentiate between chromosome- and
      plasmid-encoded resistances. Methods: We developed a MALDI-TOF MS-based method,
      named the MALDIxin test, which allows the detection of polymyxin resistance
      related modifications to lipid A (i.e. pETN addition), on intact bacteria, in <15
      min. Results: Using a characterized collection of polymyxin-susceptible and 
      resistant Escherichia coli, we demonstrated that our method is able to identify
      polymyxin-resistant isolates in 15 min whilst simultaneously discriminating
      between chromosome- and plasmid-encoded resistance. We validated the MALDIxin
      test on different media, using fresh and aged colonies and show that it
      successfully detects all MCR-1 producers in a blindly analysed set of
      carbapenemase-producing E. coli strains. Conclusions: The MALDIxin test is an
      accurate, rapid, cost-effective and scalable method that represents a major
      advance in the diagnosis of polymyxin resistance by directly assessing lipid A
      modifications in intact bacteria.

PMID- 30184213
TI  - Relationship Between Opioid Analgesic Prescription and Unemployment in Patients
      Seeking Acupuncture for Chronic Pain in Urban Primary Care.
AB  - Objective: The widespread use of opioid analgesics to treat chronic nonmalignant
      pain has contributed to the ongoing epidemic of opioid-related morbidity and
      mortality. Previous studies have also demonstrated a relationship between opioid
      analgesic use and unemployment due to disability. These studies have been limited
      to mainly white European and North American populations. The objective of this
      study is to explore the relationship between opioid analgesic use for chronic
      nonmalignant pain in an urban, mainly black and Hispanic, low-income population.
      Design: This is a cross-sectional observational study. Setting: Subjects were
      recruited from six urban primary care health centers. Subjects: Adults with
      chronic neck, back, or osteoarthritis pain participating in an acupuncture trial
      were included. Methods: Survey data were collected as a part of the Acupuncture
      Approaches to Decrease Disparities in Pain Treatment two-arm (AADDOPT-2)
      comparative effectiveness trial. Participants completed a baseline survey
      including employment status, opioid analgesic use, the Brief Pain Inventory, the
      global Patient Reported Outcomes Measurement Information Systems quality of life
      measure, the Patient Health Questionnaire-9 (PHQ-9), and demographic information.
      A multivariable logistic regression model was built to examine the association
      between opioid analgesic use and unemployment. Results: Opioid analgesic use was
      associated with three times the odds of unemployment due to disability while
      controlling for potential confounders, including depression, pain severity, pain
      interference, global physical and mental functioning, and demographic
      characteristics. Conclusions: This study adds to the growing body of evidence
      that opioid analgesics should be used with caution in chronic nonmalignant pain.

PMID- 30184215
TI  - Demethylation and epigenetic modification with 5-Azacytidine reduces IDH1 mutant
      glioma growth in combination with Temozolomide.
AB  - Background: Isocitrate Deyhydrogenase (IDH) mutant gliomas are comprised of the
      majority of grade II-III gliomas and nearly all secondary glioblastomas. These
      progressive gliomas arise from mutations in IDH1 or IDH2 that pathologically
      produces D-2-hydroxyglutarate (2HG). 2-HG interferes with cell reactions using
      alpha ketoglutarate leading to a hypermethylated genome and epigenetic
      dysregulation of gene expression initiating tumorigenesis. Methods: Human IDH1 WT
      and IDH1R132H cell lines and patient derived xenografts (PDX) were used to
      evaluate the FDA-approved DNA demethylating agent 5-Azacytidine (5-Aza). Cell
      growth, protein and gene expression, chromatin immunoprecipitation, and
      nucleosome position assays were performed in 5-Aza treated cells. To evaluate
      antitumor activity in vivo, 5-Aza was administered alone and in combination with
      Temozolomide (TMZ) in a patient-derived xenograft (PDX) glioma models harboring
      IDH1R132H mutation. Results: 5-Aza treatment has been found to reduce cell growth
      and increase Glial Fibrillary Acid Protein expression. Chromatin
      immunoprecipitation and nucleosome position assay showed that the mechanism of
      increased GFAP expression induction is associated with histone modification and
      nucleosome repositioning of the GFAP promoter, respectively. In vivo, 5-Aza
      treatment extended survival in IDH1R132H mutant, but not in an IDH1 WT glioma
      model. Additionally, 5-Aza enhances the therapeutic effect of DNA damaging agent
      TMZ in both subcutaneous and orthotopic PDX models of IDH1R132H mutant glioma.
      Conclusion: 5-Aza provides a survival benefit as a single agent but worked best
      in combination with TMZ in two different IDH1R132H mutant glioma models.

PMID- 30184216
TI  - Association between adolescent body-mass index and adulthood smoking.
AB  - Introduction: Studies increasingly find a prospective association between
      adolescent weight status and adverse physical health outcomes. However, less is
      known about the long-term consequences of adolescent body weight on the adoption
      of health risk behaviors. This study sought to determine whether adolescent body
      mass index (BMI) was associated with cigarette smoking in adulthood. Methods:
      6,683 non-smoking adolescents were interviewed at baseline (1996, age 11-20) and
      at follow-up (2008, age 24-32) as part of the National Longitudinal Survey of
      Adolescent Health. Logistic and fractional regression models tested the
      association between adolescent BMI and smoking status and frequency in adulthood.
      Respondent weight and height were measured at baseline and converted into age and
      sex-specific BMI z-scores. Being a smoker was defined as smoking at least once in
      the past 30 days, while smoking frequency was defined as the proportion of days
      smoked over the past 30 days. Both outcomes were measured at follow-up. Results:
      Adolescent BMI was positively associated with the transition from non-smoking to
      smoking 12 years later for women but not men. Adolescent BMI was also positively
      associated with smoking frequency among women smokers. Both associations
      persisted after adjusting for established risk factors and were robust to
      sensitivity analyses. Conclusion: Adolescent BMI was strongly associated with
      increased cigarette smoking behavior in adulthood for women, even after adjusting
      for important risk factors. Implications: Using a large, nationally
      representative sample, this study found that adolescent BMI was positively
      associated with smoking behavior during adulthood for women but not men. These
      results have potentially important public health implications for future smoking
      rates in the US, as the prevalence of overweight and obesity among US adolescent
      females continues to grow. Thus, it may be important for smoking prevention
      interventions to prioritize overweight adolescent females moving forward.

PMID- 30184214
TI  - Molecular Characterization and Expression Analysis of Two Acetylcholinesterase
      Genes From the Small White Butterfly Pieris rapae (Lepidoptera: Pieridae).
AB  - Acetylcholinesterases (AChEs) are essential for the hydrolysis of the
      neurotransmitter acetylcholine and play crucial roles in the termination of
      neurotransmission. AChEs are encoded by the ace genes. However, the ace genes
      from the small white butterfly, Pieris rapae (L.) (Lepidoptera: Pieridae),
      remained uncharacterized. In this study, two aces (Prace1 and Prace2) were
      identified from P. rapae. Prace1 encoded a PrAChE1 protein consisting of 694
      amino acid residues, and Prace2 encoded the 638-amino-acid PrAChE2. The two
      identified PrAChEs both had features typical of AChEs, including the catalytic
      triad, choline-binding sites, an oxyanion hole, an acyl pocket, a peripheral
      anionic subsite, an FGESAG motif and 14 conserved aromatic amino acids.
      Phylogenetic analysis showed that Prace1 and Prace2 were clustered into two
      distinct groups: ace1 and ace2, respectively. The two Praces were distributed on
      different genomic scaffolds: Prace1 on scaffold 156 and Prace2 on scaffold 430.
      Additionally, Prace1 consisted of three exons and two introns, whereas Prace2
      consisted of six exons and five introns. One amino acid mutation (Gly324Ala) in
      PrAChE1 and two (Ser291Gly and Ser431Phe) in PrAChE2 were consistent with
      mutations in other insect AChEs that are associated with insecticide
      insensitivity. Both Prace1 and Prace2 were highly expressed at the fifth-instar
      larval stage and in the larval head, and the transcriptional levels of Prace1
      were significantly higher than those of Prace2 in all of the tested life stages
      and tissues. This is the first report characterizing two ace genes in P. rapae.
      The results pave the way for functional study of these genes.

PMID- 30184217
TI  - Pediatric Tetanus in Central Pennsylvania.
AB  - Approximately 20% of the nationally reported tetanus infections in children aged
      0 to 14 years that occurred in the United States between 2005 and 2015 were
      treated at Penn State Children's Hospital. With an electronic medical record
      search, we identified 5 cases of pediatric tetanus; 100% of these cases occurred
      in unimmunized children. Their median length of stay was 10 days, and the costs
      were significant.

PMID- 30184218
TI  - In vivo cleavage rules and target repertoire of RNase III in Escherichia coli.

PMID- 30184220
TI  - Simultaneous formulation of influenza vaccine and chitosan nanoparticles within
      CpG oligodesoxi nucleotides leads to dose-sparing and protects against lethal
      challenge in the mouse model.
AB  - Lack of efficient delivery systems for transporting antigenic molecules to the
      cytosol of antigen-presenting cells presents a major obstacle for antigen uptake
      by immune cells. To this end, influenza whole inactivated virus vaccines were
      formulated with chitosan nanoparticles and CpG oligonucleotide as a biodegradable
      delivery system and a Th1-specific adjuvant, respectively. Intradermal injections
      of a single high dose and low dose of formulated candidate vaccines were carried
      out. Thirty days after injection, cell proliferation assay (MTT), IFN-gamma and
      IL-4 ELISpot assays were conducted. Sera samples were collected 21 days after
      immunization to measure IgG1 and IgG2a levels. In addition, the mice challenged
      with mouse-adopted virus were monitored for weight loss. The results show a
      significant stimulation of both humoral and cellular immunities; also, weight
      gain and a decrease in mortality in the mice receiving both dosages of
      inactivated influenza virus vaccines with CpG and Chitosan coating were observed.
      Based on the results, it can be concluded that formulation of inactivated
      influenza virus with CpG and its delivery by chitosan as low-dose can return the
      same results as with high-dose balanced between cellular and humeral immune
      responses. This formulation could potentially lead to a significant saving in
      vaccine production.

PMID- 30184221
TI  - Ex Vivo Enteroids Recapitulate In Vivo Citrulline Production in Mice.
AB  - Background: The endogenous production of arginine relies on the synthesis of
      citrulline by enteral ornithine transcarbamylase (OTC). Mutations in the gene
      coding for this enzyme are the most frequent cause of urea cycle disorders. There
      is a lack of correlation between in vivo metabolic function and DNA sequence,
      transcript abundance, or in vitro enzyme activity. Objective: The goal of the
      present work was to test the hypothesis that enteroids, a novel ex vivo model,
      are able to recapitulate the in vivo citrulline production of wild-type (WT) and
      mutant mice. Methods: Six-week-old male WT and OTC-deficient mice [sparse fur and
      abnormal skin (spf-ash) mutation] were studied. Urea and citrulline fluxes were
      determined in vivo, and OTC abundance was measured in liver and gut tissue.
      Intestinal crypts were isolated and cultured to develop enteroids. Ex vivo
      citrulline production and OTC abundance were determined in these enteroids.
      Results: Liver OTC abundance was lower (mean +/- SE: 0.16 +/- 0.01 compared with
      1.85 +/- 0.18 arbitrary units; P < 0.001) in spf-ash mice than in WT mice, but
      there was no difference in urea production. In gut tissue, OTC was barely
      detectable in mutant mice; despite this, a lower but substantial citrulline
      production (67 +/- 3 compared with 167 +/- 8 umol . kg-1 . h-1; P < 0.001) was
      shown in the mutant mice. Enteroids recapitulated the in vivo findings of a very
      low OTC content accompanied by a reduced citrulline production (1.07 +/- 0.20
      compared with 4.64 +/- 0.44 nmol . ug DNA-1 . d-1; P < 0.001). Conclusions:
      Enteroids recapitulate in vivo citrulline production and offer the opportunity to
      study the regulation of citrulline production in a highly manipulable system.

PMID- 30184222
TI  - Complementary Food Supplements Increase Dietary Nutrient Adequacy and Do Not
      Replace Home Food Consumption in Children 6-18 Months Old in a Randomized
      Controlled Trial in Rural Bangladesh.
AB  - Background: Inadequate complementary feeding is common in low- and middle-income
      countries, contributing to growth deficits. Complementary food supplements (CFSs)
      aim to fill dietary gaps, but few CFS studies have measured nutrient intake. In a
      community-based, randomized CFS trial in Bangladesh, we previously reported poor
      dietary diversity in 6-18-mo-old participants. Objective: We investigated, in a
      secondary analysis in the same trial, micronutrient intake adequacy in
      supplemented compared with control-arm children. Methods: At age 6 mo, children
      were assigned to 1 y of child-feeding counseling for mothers (control) or
      counseling plus 1 of 4 CFS formulations. Mothers were administered quantitative
      past 24-h diet questionnaires for their children at ages 6, 9, 12, 15, and 18 mo.
      Nutrient intakes were estimated with local recipes and food composition tables
      assuming average age-specific breastmilk intake. Adequacy was evaluated relative
      to estimated average requirements or adequate intakes. Multivariate analysis of
      variance and generalized estimating equation (GEE) regression models estimated
      the effect of each CFS on nutrient adequacy. GEE models tested dietary predictors
      of nutrient adequacy in the control arm. Results: A total of 25,964 dietary
      modules across 5 interviews were completed. Nutrient adequacy from home foods
      combined with assumed breastmilk intake was low. Only 5 of 16 micronutrients were
      adequately consumed by >60% of children at 18 mo of age. Daily CFSs did not
      affect energy-adjusted micronutrient intake from home foods at any follow-up age
      (P > 0.05). CFSs increased the mean adequacy ratio for all micronutrients (P <
      0.001 at all ages), to >=1 for 14 of 16 micronutrients at 18 mo. Dietary
      diversity predicted adequate iron, zinc and calcium intake at 15 mo in
      unsupplemented controls. Conclusions: Home foods did not meet the estimated
      micronutrient needs of 9-18-mo-old children in rural Bangladesh. Daily
      supplementation with fortified complementary foods filled many micronutrient
      intake gaps and did not displace home foods. Previously, CFSs were shown to also
      improve linear growth and reduce stunting in this cohort. Findings support the
      need for CFSs in similar settings to promote nutritional well being and growth.
      This trial was registered at clinicaltrials.gov as NCT01562379.

PMID- 30184223
TI  - PROCOMIDA, a Food-Assisted Maternal and Child Health and Nutrition Program,
      Reduces Child Stunting in Guatemala: A Cluster-Randomized Controlled Intervention
      Trial.
AB  - Background: Food-assisted maternal and child health and nutrition (FA-MCHN)
      programs may foster child growth during the first 1000 d (pregnancy and the first
      2 y of a child's life), but evidence is scant. Objective: We evaluated the impact
      of an FA-MCHN program, PROCOMIDA, on linear growth (stunting [length-for-age z
      score (LAZ) < -2] and length-for-age difference [LAD]) among children aged 1-24
      mo. PROCOMIDA was implemented in Guatemala by Mercy Corps and was available to
      beneficiaries throughout the first 1000 d. Methods: We used a longitudinal,
      cluster-randomized controlled trial with groups varying in family ration sizes
      [full (FFR), reduced (RFR), and none (NFR)] and individual ration types provided
      to mothers (pregnancy to 6 mo postpartum) and children (6-24 mo of age) [corn-soy
      blend (CSB), lipid-based nutrient supplement (LNS), micronutrient powder (MNP)]:
      1) FFR + CSB (n = 576); 2) RFR + CSB (n = 575); 3) NFR + CSB (n = 542); 4) FFR +
      LNS (n = 550); 5) FFR + MNP (n = 587); 6) control (n = 574). Program impacts
      compared with control, and differential impacts between groups varying family
      ration size or individual ration type, were assessed through the use of linear
      mixed-effects models and post hoc simple effect tests (significant if P < 0.05).
      Results: PROCOMIDA significantly reduced stunting at age 1 mo in FFR + CSB, RFR +
      CSB, and FFR + MNP groups compared with control [5.05, 4.06, and 3.82 percentage
      points (pp), respectively]. Stunting impact increased by age 24 mo in FFR + CSB
      and FFR + MNP relative to control (impact = 11.1 and 6.5 pp at age 24 mo,
      respectively). For CSB recipients, the FFR compared with RFR or NFR significantly
      reduced stunting (6.47-9.68 pp). CSB reduced stunting significantly more than LNS
      at age 24 mo (8.12 pp). Conclusions: FA-MCHN programs can reduce stunting during
      the first 1000 d, even in relatively energy/food-secure populations. Large family
      rations with individual rations of CSB or MNP were most effective. The widening
      of impact as children age highlights the importance of intervening throughout the
      full first 1000 d. This trial was registered at clinicaltrials.gov as
      NCT01072279.

PMID- 30184224
TI  - Circulating gamma-Tocopherol Concentrations Are Inversely Associated with
      Antioxidant Exposures and Directly Associated with Systemic Oxidative Stress and
      Inflammation in Adults.
AB  - Background: Although alpha- and gamma-tocopherol are co-consumed antioxidants,
      circulating gamma-tocopherol concentrations were paradoxically found to be
      inversely associated with total vitamin E intake and circulating alpha-tocopherol
      concentrations. There are limited data on this apparent paradox or on
      determinants of circulating gamma-tocopherol concentrations. Objective: To help
      clarify possible determinants of circulating gamma-tocopherol concentrations, we
      investigated associations of circulating gamma-tocopherol concentrations with
      various dietary and lifestyle factors and biomarkers of oxidative stress and
      inflammation. Methods: We pooled cross-sectional data from 2 outpatient, adult,
      elective colonoscopy populations (pooled n = 419) on whom extensive dietary,
      lifestyle, and medical information was collected, and the following plasma
      concentrations were measured: alpha- and gamma-tocopherol (via HPLC), F2
      isoprostanes (FiPs; via gas chromatography-mass spectrometry), and high
      sensitivity C-reactive protein (hsCRP; via latex-enhanced immunonephelometry).
      Multivariable general linear models were used to assess mean gamma-tocopherol
      differences across quantiles of plasma antioxidant micronutrients, FiPs, and
      hsCRP; an oxidative balance score [OBS; a composite of anti- and pro-oxidant
      dietary and lifestyle exposures (a higher score indicates higher antioxidant
      relative to pro-oxidant exposures)]; and multiple dietary and lifestyle factors.
      Results: Adjusted for serum total cholesterol, mean gamma-tocopherol
      concentrations among those in the highest relative to the lowest tertiles of
      circulating alpha-tocopherol and beta-carotene, the OBS, and total calcium and
      dietary fiber intakes were 31.0% (P < 0.0001), 29.0% (P < 0.0001), 27.6% (P =
      0.0001), 29.7% (P < 0.0001), and 18.6% (P = 0.008) lower, respectively. For those
      in the highest relative to the lowest tertiles of circulating FiPs and hsCRP,
      mean gamma-tocopherol concentrations were 50% (P < 0.0001) and 39.0% (P < 0.0001)
      higher, respectively. Conclusions: These findings support the conclusion that
      circulating gamma-tocopherol concentrations are inversely associated with
      antioxidant exposures and directly associated with systemic oxidative stress and
      inflammation in adults. Additional research on possible mechanisms underlying
      these findings and on whether circulating gamma-tocopherol may serve as a
      biomarker of oxidative stress, inflammation, or both is needed.

PMID- 30184225
TI  - Reply to B Fromm et al.

PMID- 30184226
TI  - Lysine Stimulates Protein Synthesis by Promoting the Expression of ATB0,+ and
      Activating the mTOR Pathway in Bovine Mammary Epithelial Cells.
AB  - Background: l-lysine (Lys) is a critical dietary nutrient for mammary gland
      development and milk production. However, the specific pathways of Lys
      utilization and how milk protein synthesis is affected in bovine mammary
      epithelial cells (BMECs) are poorly understood. Objective: We aimed to
      investigate the effects of Lys on milk protein synthesis and the mechanism of Lys
      uptake and catabolism in BMECs. Methods: BMECs were cultured in 0, 0.5, 1.0, 1.5,
      2.0, 5.0, and 10.0 mmol Lys/L to detect cell viability, or cultured in 0-2.0 mmol
      Lys/L with l-[ring-3H5] phenylalanine to study the effect of Lys on protein
      turnover, or cultured in Krebs buffer with [U-14C] l-Lys to quantify Lys
      metabolism. In some experiments, BMECs were cultured in a conditioned medium
      alone or including 1.0 mmol Lys/L and 2-amino-endo-bicyclo [2.2.1] heptane-2
      carboxylic acid (BCH) for 24 h to analyze the expression of amino acid
      transporter B (0+) (ATB0,+), mammalian target of rapamycin (mTOR), and Janus
      kinase 2 (JAK2)-signal transducer and activator of transcription 5 (STAT5)
      pathways. Results: Including 1.0 mmol Lys/L in cultures increased cell viability
      by 17-47% and protein synthesis by 7-23%, whereas protein degradation was
      inhibited by 4-64% compared with BMECs cultured with 0, 0.5, or 2.0 mmol Lys/L
      (all P <= 0.05). Studies that used [U-14C] l-Lys showed that most Lys was
      incorporated into proteins (90%), whereas the remainder was either oxidized into
      CO2 (4%) or used as a substrate for aspartate (3%) and histidine synthesis (3%).
      Furthermore, Lys significantly increased expression of ATB0,+ (71% mRNA and 44%
      protein), STAT5 (27% mRNA and 21% phosphorylated proteins), and mTOR (51% mRNA
      and 22% phosphorylated proteins) compared with cells without Lys. Conclusions:
      Lys promoted protein synthesis, mostly through enhancing uptake by ATB0,+ and the
      mTOR and JAK2-STAT5 pathways. Understanding the utilization of Lys in BMECs
      provides insights into the role of amino acid nutrition in bovine milk
      production.

PMID- 30184227
TI  - Dietary Patterns Affect the Gut Microbiome-The Link to Risk of Cardiometabolic
      Diseases.
AB  - Clusters of bacterial species within the gut microenvironment, or gut enterotype,
      have been correlated with cardiometabolic disease risk. The metabolic products
      and metabolites that bacteria produce, such as short-chain fatty acids, secondary
      bile acids, and trimethylamine, may also affect the microbial community and
      disease risk. Diet has a direct impact on the gut microenvironment by providing
      substrates to and promoting the colonization of resident bacteria. To date, few
      dietary patterns have been evaluated for their effect on the gut microbiome, but
      the Mediterranean diet and Vegetarian diets have shown favorable effects for both
      the gut microbiome and cardiometabolic disease risk. This review examines the gut
      microbiome as a mediator between these dietary patterns and cardiometabolic
      disease risk.

PMID- 30184228
TI  - Human and Cow Have Identical miR-21-5p and miR-30a-5p Sequences, Which Are Likely
      Unsuited to Study Dietary Uptake from Cow Milk.

PMID- 30184229
TI  - Yet Again, Serum Zinc Concentrations Are Unrelated to Zinc Intakes.

PMID- 30184230
TI  - Better Nutritional Status Is Positively Associated with mRNA Expression of SIRT1
      in Community-Dwelling Older Adults in the Toledo Study for Healthy Aging.
AB  - Background: The expression of certain genes involved in response to oxidative
      stress is likely related to aging-related outcomes, such as frailty in old age.
      Given nutrition's substantial impact in aging and age-related diseases, one of
      its mechanisms might be through influencing gene expression. Objective: This
      study aimed to investigate the association between nutrition and the expression
      of 15 genes related to cellular response to stress in older community-dwelling
      individuals. Methods: A nested case-control study of 350 participants (mean +/-
      SEM age: 76.5 +/- 6.9 y, 42.9% men, 22% frail according to Fried's criteria) was
      selected from the Toledo Study for Healthy Aging. Blood-derived RNA was retro
      transcribed into complementary DNA. TaqMan Arrays were used for determining gene
      expression. The Mini Nutritional Assessment (MNA) and the PREDIMED (PREvencion
      con DIeta MEDiterranea) questionnaire measured nutritional status and adherence
      to the Mediterranean diet (MD), respectively. Data were reweighed so that
      inference from linear and logistic regression models applied to the original
      sampling population. Results: Higher MNA scores were associated with higher
      expressions of the gene coding for sirtuin-1 (SIRT1), regardless of age, sex, and
      Charlson comorbidity score (P = 0.04) and even after adjusting for frailty status
      (P = 0.016) and level of adherence to the MD (P = 0.04). Malnutrition risk and
      SIRT1 gene expression were inversely associated (P = 0.0045) independently of
      frailty status (P = 0.0045) and level of adherence to the MD (P = 0.0075).
      Conclusions: In older individuals, improvement in nutritional status is
      positively associated with SIRT1 gene expression independently of frailty status
      or adherence to the MD. These findings may provide potential biomarkers and
      targets for health interventions among the elderly.

PMID- 30184231
TI  - Investigating the predictors of workplace embitterment using a longitudinal
      design.
AB  - Background: Embitterment has been described as the emotion generated by an event
      experienced as unjust. Although clinicians working in occupational health
      services readily recognize features of embitterment in organizations, little
      attention has been given to workplace embitterment. Research is warranted to
      identify predictors and features of employees' embitterment. Aims: To explore the
      predictors and the chronicity of workplace embitterment over 6 months. Methods: A
      longitudinal study investigating the chronicity of workplace embitterment and its
      antecedents among employees from various occupations. Data were collected by
      online questionnaires including measures of workplace embitterment,
      organizational justice and employees' perceptions of supervisory control.
      Results: The survey was completed by 352 employees at Time 1, and 169 at Time 2.
      The final sample (assessed at two time points) was 147 employees. The feeling of
      workplace embitterment appeared to be very stable during the 6-month period.
      Hierarchical regression analysis revealed that perceptions of distributive
      injustice, informational injustice and employees' perceptions on supervisory over
      control in Time 1 significantly predicted embitterment in Time 2. Only the
      relationship between employees' perceptions of supervisory control and
      embitterment remained significant after controlling for baseline levels of
      embitterment. Conclusions: This study provides evidence for the negative impact
      perceived organizational injustice can have on employees' experience of workplace
      embitterment. Results indicate that employees who perceive their supervisor as
      being over-controlling are more likely to suffer from workplace embitterment. The
      finding that workplace embitterment is stable during a 6-month period highlights
      the need for effective interventions in ameliorating and preventing workplace
      embitterment.

PMID- 30184233
TI  - Performance of creatinine-based equations for estimating glomerular filtration
      rate changes over time.
AB  - Background: Glomerular filtration rate (GFR) is commonly used to monitor chronic
      kidney disease (CKD) progression, but its validity for evaluating kidney function
      changes over time has not been comprehensively evaluated. We assessed the
      performance of creatinine-based equations for estimating GFR slope according to
      patient characteristics and specific CKD diagnosis. Methods: In the NephroTest
      cohort study, we measured GFR 5324 times by chromium 51-labeled ethylenediamine
      tetraacetic acid renal clearance in 1955 adult patients with CKD Stages 1-4
      referred to nephrologists (Stages 1-2, 19%) and simultaneously estimated GFR with
      both the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and
      Modification of Diet in Renal Disease (MDRD) equations for isotope dilution mass
      spectrometry traceable creatinine; absolute and relative GFR slopes were
      calculated using a linear mixed model. Results: Over a median follow-up of 3.4
      [interquartile range (IQR) 2.0-5.6] years, the decline in mean absolute and
      relative measured GFR (mGFR) and CKD-EPI and MDRD estimated GFR (eGFR) was 1.6 +/
      1.2, 1.5 +/- 1.4 and 1.3 +/- 1.3 mL/min/1.73 m2/year and 5.9 +/- 5.3, 5.3 +/-
      5.3 and 4.8 +/- 5.2%/year, respectively; 52% and 55% of the patients had MDRD and
      CKD-EPI eGFR slopes within 30% of mGFR slopes. Both equations tended to
      overestimate the GFR slope in the youngest patients and underestimate it in the
      oldest, thus producing inverse associations between age and mGFR versus eGFR
      slope. Other patient characteristics and specific CKD diagnoses had little effect
      on the performance of the equations in estimating associations. Conclusions: This
      study shows little bias, but poor precision in GFR slope estimation for both MDRD
      and CKD-EPI equations. Importantly, bias strongly varied with age, possibly due
      to variations in muscle mass over time, with implications for clinical care and
      research.

PMID- 30184232
TI  - Associations between polysomnography and actigraphy-based sleep indices and
      glycemic control among those with and without type 2 diabetes: the Multi-Ethnic
      Study of Atherosclerosis.
AB  - Study Objectives: To examine the associations of sleep measures with hemoglobin
      A1c (HbA1c) among individuals with and without type 2 diabetes. Methods: Data
      were from 2049 Multi-Ethnic Study of Atherosclerosis participants taking part in
      a sleep ancillary study. Cross-sectional linear regression models examined
      associations of actigraphy estimates of sleep (sleep duration, variability, and
      maintenance efficiency) and polysomnography measures (obstructive sleep apnea
      [OSA] and hypoxemia) with HbA1c, stratified by diabetes status. Primary models
      were adjusted for demographics, lifestyle behaviors, and obesity. Results: Among
      individuals with diabetes (20 per cent population), those who slept <5 hr/night
      had greater HbA1c than those who slept 7-8 hr/night (7.44 vs. 6.98 per cent,
      ptrend = 0.04), with no attenuation of associations after adjusting for
      OSA/hypoxemia. In women with diabetes, but not men, those in the lowest quartile
      of sleep maintenance efficiency had greater HbA1c than those in the highest
      quartile of sleep maintenance efficiency (7.60 vs. 6.97 per cent, ptrend < 0.01).
      Among those without diabetes, individuals with severe OSA or in the highest
      quartile of hypoxemia had significantly greater HbA1c than those without OSA or
      who were in the lowest quartile of hypoxemia (5.76 vs. 5.66 per cent, ptrend =
      0.01; 5.75 vs. 5.66 per cent, ptrend < 0.01, respectively). Associations did not
      meaningfully differ by race/ethnicity. Conclusions: Among individuals with
      diabetes, HbA1c was significantly higher in men and women with short sleep
      duration and in women with poor sleep maintenance efficiency, suggesting a role
      for behavioral sleep interventions in the management of diabetes. Among
      individuals without diabetes, untreated severe OSA/hypoxemia may adversely
      influence HbA1c.

PMID- 30184234
TI  - Cumulative exposure to air pollution and subsequent mortality among older adults
      in China.
AB  - Background: Research on the health effects of exposure to air pollution is
      growing. However, relatively little attention has been paid to the effects of
      long-term and cumulative exposure to air pollutants. Individual-level studies on
      the health consequences of air pollution in China are especially scarce. The
      purpose of this study is to examine the effect of cumulative exposure to sulfur
      dioxide (SO2), an air pollutant of particular concern in China, on all-cause
      mortality in older Chinese adults. Methods: Using a nationally representative
      sample of older adults in China (N = 11 199), we tracked mortality over an 11
      year period (2000-11). Air pollution data were linked to respondents using
      provincial identifiers. To examine the effect of cumulative SO2 exposure on
      mortality, we employed multilevel multinomial logistic regression models that
      account for within subject clustering of observations over time and clustering at
      the province level. Results: We found that every 10-MUg/m3 increase in cumulative
      exposure to SO2 increased the odds of death by nearly 1% (OR = 1.008; 95% CI:
      1.002-1.014), controlling for province- and individual-level social and economic
      characteristics. Conclusions: Our analysis shows that air pollution is a risk
      factor for morality in older Chinese adults. Findings suggest that stronger SO2
      regulations may enhance longevity.

PMID- 30184235
TI  - Effect of MAPK Inhibition on the Differentiation of a Rhabdomyosarcoma Cell Line
      Combined With CRISPR/Cas9 Technology: An In Vitro Model of Human Muscle Diseases.
AB  - The human rhabdomyosarcoma cell line TE671 has been used extensively to study
      different aspects of muscle biology. However, its ability to differentiate and
      form myotubes has not been explored. Here, we examined muscle differentiation
      when we specifically stopped proliferation of human TE671 (WT-TE671) cells by
      using 1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio]butadiene (U0126), an
      MAPK inhibitor. Our data show that treated cells initiated fusion, and myotube
      formation and that expression levels of dysferlin and myogenin were increased,
      whereas those of pax7 were decreased. Treatment of WT-TE671 cells with vitamin D3
      alone and cotreatment with U0126 also promoted dysferlin expression. In addition,
      we knocked out the DYSF gene, which is involved in muscle differentiation, using
      CRISPR/Cas9 technology in WT-TE671 cells (Dysf-KO TE671). No dysferlin expression
      was observed before and after U0126 treatment. Although myogenin expression was
      absent in vehicle-treated Dysf-KO TE671 cells, after addition of U0126, myogenin
      reached levels similar to WT-TE671. This widely available source of human cells
      appropriately treated with U0126 may represent a useful model to study human
      muscle physiology in vitro. This dysferlin-deficient cell line should allow the
      study of pathophysiological pathways involved in dysferlin-deficient muscle and
      constitute a tool for high-throughput screening of therapeutic compounds for
      patients with dysferlinopathy and other muscle diseases.

PMID- 30184236
TI  - Cleaning agent occupational asthma in the West Midlands, UK: 2000-16.
AB  - Background: Cleaning agents are now a common cause of occupational asthma (OA)
      worldwide. Irritant airway and sensitization mechanisms are implicated for a
      variety of old and new agents. Aims: To describe the exposures responsible for
      cleaning agent OA diagnosed within a UK specialist occupational lung disease
      service between 2000 and 2016. Methods: The Birmingham NHS Occupational Lung
      Disease Service clinical database was searched for cases of OA caused by cleaning
      agents, and data were gathered on age, gender, atopic status, smoking history,
      symptom onset, diagnostic investigations (including Occupational Asthma SYStem
      analysis of workplace serial peak expiratory flow measurements and specific
      inhalational challenge), proposed mechanism, industry, occupation and causative
      agent. Results: Eighty patients with cleaning agent OA (77% female, 76% arising
      de novo) were identified. The median annual number of cases was 4 (interquartile
      range = 2-7). The commonest cleaning agents causing OA were chloramines (31%),
      glutaraldehyde (26%) and quaternary ammonium compounds (11%) and frequently
      implicated industries were healthcare (55%), education (18%) and leisure (8%).
      Conclusions: Certain cleaning agents in common usage, such as chlorine-releasing
      agents, quaternary ammonium compounds and aldehydes, are associated with
      sensitization and asthma. Their use alters over time, and this is particularly
      evident in UK healthcare where cleaning and decontamination practice and policy
      have changed. Vigilance for OA in workplaces such as hospitals, nursing homes,
      leisure centres and swimming pools, where these cleaning agents are regularly
      used, is therefore essential.

PMID- 30184237
TI  - Trends and Patient Characteristics Associated with Tobacco Pharmacotherapy
      Dispensed in the Veterans Health Administration.
AB  - Introduction: There is evidence suggesting that certain subgroups of people who
      use tobacco do not receive tobacco pharmacology as consistently as others.
      Methods: This retrospective, cohort study examined the trend in the use of
      cessation pharmacotherapy from 2004 to 2013 using Veterans Health Administration
      (VHA) administrative data. Among Veterans who used tobacco in the fiscal year
      (FY) 2011 and had not received pharmacotherapy in the prior year, multivariable
      Cox regression was used to assess the independent associations between patient
      clinical and demographic characteristics and pharmacotherapy initiation in the 6
      months follow-up period. Results: Smoking cessation pharmacotherapy in the VHA
      increased from 13.8% in 2004 to 25.6% in 2013. In 2011, Veterans (N = 838309) who
      were more likely to newly receive pharmacotherapy included those with psychiatric
      disorders (depression, bipolar disorder, non-alcohol substance use disorder,
      other anxiety, and post-traumatic stress disorder), chronic pulmonary disease,
      peripheral vascular disorders, and younger Veterans (adjusted rate ratios (ARRs)
      ranged from 1.03 to 1.92, all p < .001). Veterans less likely to receive
      pharmacotherapy were those with schizophrenia or other psychosis, males,
      Hispanics, and those with a medical condition (uncomplicated diabetes,
      uncomplicated hypertension, fluid and electrolyte disorders, cardiac arrhythmia,
      valvular disease, hypothyroidism, acquired immunodeficiency syndrome/human
      immunodeficiency virus, deficiency anemia, renal failure, paralysis,
      coagulopathy, metastatic cancer, and other neurological disorders) (ARRs ranged
      from 0.74 to 0.93, all p < .001). Conclusions: Although VHA cessation
      pharmacotherapy use nearly doubled from 13.8% in 2004 to 25.6% in 2013, reaching
      undertreated subgroups, especially those with medical comorbidities, may improve
      cessation outcomes. Implications: Despite evidence that demographics influence
      the use of pharmacotherapy in smoking cessation, there is limited and
      contradictory information regarding how psychiatric and chronic medical illnesses
      affect pharmacotherapy use. Administrative data were used to determine trends and
      patient characteristics of those receiving pharmacotherapy to aid in smoking
      cessation in the Veterans Health Administration. From 2004 to 2013,
      pharmacotherapy use increased from 13.8% to 25.6% of current smokers. Factors
      associated with increased pharmacotherapy initiation were psychiatric disorders,
      chronic pulmonary disease, peripheral vascular disorders, and younger age.
      Veterans with schizophrenia or other psychosis, males, Hispanics, and most
      medical conditions were less likely to receive pharmacotherapy.

PMID- 30184238
TI  - Proteinuria and cholesterol reduction are independently associated with less
      renal function decline in statin-treated patients; apost hoc analysis of the
      PLANET trials.
AB  - Background: Statins have shown multiple effects on different renal risk factors
      such as lowering of total cholesterol (TC) and lowering of urine
      protein:creatinine ratio (UPCR). We assessed whether these effects of statins
      vary between individuals, the extent of discordance of treatment effects on both
      TC and UPCR within an individual, and the association of responses in TC and UPCR
      with estimated glomerular filtration rate (eGFR) decline. Methods: The PLANET I
      and II (Renal effects of Rosuvastatin and Atorvastatin in Patients Who Have
      Progressive Renal Disease) trials examined effects of atorvastatin and
      rosuvastatin on proteinuria and renal function in patients with proteinuria. We
      post hoc analysed 471 therapy-adherent proteinuric patients from the two trials
      and assessed the individual variability in UPCR and TC response from 0 to 14
      weeks and whether these responses were predictive of eGFR decline during the
      subsequent 9 months of follow-up. Results: UPCR and TC response varied between
      individuals: mean UPCR response was -1.3% (5th-95th percentile -59.9 to 141.8)
      and mean TC response was -93.9 mg/dL (-169.1 to -26.9). Out of 471 patients, 123
      (26.1%) showed a response in UPCR but not in TC, and 96 (20.4%) showed a response
      in TC but not in UPCR. eGFR (mL/min/1.73 m2) did not decrease significantly from
      baseline in both UPCR responders [0.4; 95% confidence interval (CI) -1.6 to 0.9;
      P = 0.54] and TC responders (0.3; 95% CI -1.8 to 1.1; P = 0.64), whereas UPCR and
      TC non-responders showed a significant decline in eGFR from baseline (1.8; 95% CI
      0.6-3.0; P = 0.004 and 1.7; 95% CI 0.5-2.9; P = 0.007, respectively). A lack of
      response in both parameters resulted in the fastest rate of eGFR decline (2.1;
      95% CI 0.5-3.7; P = 0.01). These findings were not different for rosuvastatin or
      atorvastatin. Conclusions: Statin-induced changes in cholesterol and proteinuria
      vary between individuals and do not run in parallel within an individual. The
      initial fall in cholesterol and proteinuria is independently associated with a
      reduction in eGFR decline. This highlights the importance of monitoring both
      cholesterol and proteinuria after initiating statin therapy.

PMID- 30184239
TI  - The relationship between Toxocara species seropositivity and allergic skin
      disorders: a systematic review and meta-analysis.
AB  - We performed a systematic review and meta-analysis on observational studies to
      evaluate the possible associations between Toxocara species seropositivity and
      allergic skin disorders (ASDs). We searched the MEDLINE, ScienceDirect, Scopus,
      Web of Science and Google Scholar databases to 15 May 2018 to identify the
      relevant studies. We used a random effects meta-analysis model to generate the
      pooled odds ratio (OR) and 95% confidence intervals (CIs). Fifteen studies,
      including eight studies with a case-control design (735 patients and 1342
      controls) and seven studies with a cross-sectional design (a total of 4804
      participants, 1302 individuals with ASDs and 3502 without ASDs), were included in
      the meta-analysis. We found an increased risk for ASDs in individuals with
      Toxocara seropositivity (OR 1.75 [95% CI 1.16 to 2.64]). Subanalysis showed that
      Toxocara seropositivity was significantly associated with urticaria (OR 2.97 [95%
      CI 1.53 to 5.76]), however, it was not significantly associated with atopy (OR
      1.08 [95% CI 0.55 to 2.15]) and eczema (OR 1.62 [95% CI 0.95 to 2.78]). Moreover,
      the pooled ORs were 2.34 (95% CI 1.32 to 4.15) and 1.27 (95% CI 0.69 to 2.35) for
      case-control and cross-sectional studies, respectively. The results of our study
      support hypotheses regarding the existence of a positive relationship between
      Toxocara infection and allergic disorders, although this association should be
      further investigated by longitudinal and mechanism studies.

PMID- 30184240
TI  - Anxiety after stroke: A systematic review and meta-analysis.
AB  - OBJECTIVE: To update the evidence surrounding the presence of anxiety after
      stroke. DATA SOURCES: A search was conducted in EMBASE, MEDLINE, PsycINFO,
      Cochrane Library, AMED and CINAHL in May 2015 and repeated in April 2017. STUDY
      SELECTION: Clinical diagnosis of stroke and assessed for anxiety symptoms on a
      rating scale in the first year after stroke. DATA EXTRACTION: One reviewer
      screened and identified studies against the inclusion criteria. A second reviewer
      conducted a random check of approximately 10% of titles and abstracts. Two
      authors independently performed the final full-text review. DATA SYNTHESIS:
      Overall pooled prevalence of anxiety disorders was 29.3% ((95% confidence
      interval 24.8-33.8%), (I2 = 97%, p < 0.00001)) during the first year. Frequency 0
      2 weeks post-stroke was 36.7%, 2 weeks to 3 months 24.1%, and 3-12 months 23.8%.
      There was a statistically high heterogeneity in this estimate (I2 = 97%, p <
      0.00001). CONCLUSION: Anxiety is common during the first year post-stroke. Since
      anxiety significantly influences quality of life and is a predictor for
      depression, it may be worth considering further routine screening post-stroke.

PMID- 30184241
TI  - Efficiency of Emergency Physicians: Insights from an Observational Study using
      EHR Log Files.
AB  - OBJECTIVE:  With federal mandates and incentives since the turn of this decade,
      electronic health records (EHR) have been widely adopted and used for clinical
      care. Over the last several years, we have seen both positive and negative
      perspectives on its use. Using an analysis of log files of EHR use, we
      investigated the nature of EHR use and their effect on an emergency department's
      (ED) throughput and efficiency. METHODS:  EHR logs of time spent by attending
      physicians on EHR-based activities over a 6-week period (n = 2,304 patients) were
      collected. For each patient encounter, physician activities in the EHR were
      categorized into four activities: documentation, review, orders, and navigation.
      Four ED-based performance metrics were also captured: door-to-provider time, door
      to-doctor time, door-to-disposition time, and length of stay (LOS). Association
      between the four EHR-based activities and corresponding ED performance metrics
      were evaluated. RESULTS:  We found positive correlations between physician review
      of patient charts, and door-to-disposition time (r = 0.43, p < 0.05), and with
      LOS (r = 0.48, p < 0.05). There were no statistically significant associations
      between any of the other performance metrics and EHR activities. CONCLUSION:  The
      results highlight that longer time spent on reviewing information on the EHR is
      potentially associated with decreased ED throughput efficiency. Balancing these
      competing goals is often a challenge of physicians, and its implications for
      patient safety is discussed.

PMID- 30184242
TI  - Characteristics of children aged 2-17 years undergoing anaesthesia in Danish
      hospitals 2005-2015: a national observational study.
AB  - Provision of paediatric anaesthesia requires careful consideration of the child's
      cognitive state, unique body composition and physiology. In an observational
      cohort study, we describe the population characteristics and conduct of
      anaesthesia in children aged 2-17 years from 1 January 2005 to 31 December 2015.
      Children were identified from the Danish Anaesthesia Database. We recorded the
      following variables: age; sex; comorbidities; indications for anaesthesia;
      practice of anaesthesia; and complications. Results are presented for two age
      groups: 2-5 and 6-17 years. In total, 32,840 (61% male) children aged 2-5 years
      received 50,484 anaesthesia episodes and 91,418 (54% male) children aged 6-17
      years received 141,082 anaesthesia episodes. The younger children, compared with
      the older children, were more frequently anaesthetised at a university hospital
      (50% vs. 36%) and for non-surgical procedures (24% vs. 8%). For both age groups,
      general anaesthesia was the primary choice of anaesthesia regardless of the
      reason for anaesthesia. For surgery, general anaesthesia using inhalational
      agents in addition to intravenous agents or alone was more frequently used in
      younger children (49% vs. 15%), whereas older children commonly received total
      intravenous anaesthesia (50% vs. 83%). Regional anaesthesia was infrequently
      utilised. Complications occurred in 3.3% of anaesthesia episodes among 2-5 year
      olds compared with 3.7% of anaesthesia episodes among children aged 6-17 years.
      In conclusion, we found younger children (aged 2-5), compared with older children
      (aged 6-17) were more frequently anaesthetised for non-surgical reasons, at a
      university hospital and using inhalational agents. Complications were rare.

PMID- 30184243
TI  - Head-to-head trials of antibiotics for bronchiectasis.
AB  - BACKGROUND: The diagnosis of bronchiectasis is defined by abnormal dilation of
      the airways related to a pathological mechanism of progressive airway destruction
      that is due to a 'vicious cycle' of recurrent bacterial infection, inflammatory
      mediator release, airway damage, and subsequent further infection. Antibiotics
      are the main treatment option for reducing bacterial burden in people with
      exacerbations of bronchiectasis and for longer-term eradication, but their use is
      tempered against potential adverse effects and concerns regarding antibiotic
      resistance. The comparative effectiveness, cost-effectiveness, and safety of
      different antibiotics have been highlighted as important issues, but currently
      little evidence is available to help resolve uncertainty on these questions.
      OBJECTIVES: To evaluate the comparative effects of different antibiotics in the
      treatment of adults and children with bronchiectasis. SEARCH METHODS: We
      identified randomised controlled trials (RCTs) through searches of the Cochrane
      Airways Group Register of trials and online trials registries, run 30 April 2018.
      We augmented these with searches of the reference lists of published studies.
      SELECTION CRITERIA: We included RCTs reported as full-text articles, those
      published as abstracts only, and unpublished data. We included adults and
      children (younger than 18 years) with a diagnosis of bronchiectasis by
      bronchography or high-resolution computed tomography who reported daily signs and
      symptoms, such as cough, sputum production, or haemoptysis, and those with
      recurrent episodes of chest infection; we included studies that compared one
      antibiotic versus another when they were administered by the same delivery
      method. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed
      trial selection, data extraction, and risk of bias. We assessed overall quality
      of the evidence using GRADE criteria. We made efforts to collect missing data
      from trial authors. We have presented results with their 95% confidence intervals
      (CIs) as mean differences (MDs) or odds ratios (ORs). MAIN RESULTS: Four
      randomised trials were eligible for inclusion in this systematic review - two
      studies with 83 adults comparing fluoroquinolones with beta-lactams and two
      studies with 55 adults comparing aminoglycosides with polymyxins.None of the
      included studies reported information on exacerbations - one of our primary
      outcomes. Included studies reported no serious adverse events - another of our
      primary outcomes - and no deaths. We graded this evidence as low or very low
      quality. Included studies did not report quality of life. Comparison between
      fluoroquinolones and beta-lactams (amoxicillin) showed fewer treatment failures
      in the fluoroquinolone group than in the amoxicillin group (OR 0.07, 95% CI 0.01
      to 0.32; low-quality evidence) after 7 to 10 days of therapy. Researchers
      reported that Pseudomonas aeruginosa infection was eradicated in more
      participants treated with fluoroquinolones (Peto OR 20.09, 95% CI 2.83 to 142.59;
      low-quality evidence) but provided no evidence of differences in the numbers of
      participants showing improvement in sputum purulence (OR 2.35, 95% CI 0.96 to
      5.72; very low-quality evidence). Study authors presented no evidence of benefit
      in relation to forced expiratory volume in one second (FEV1). The two studies
      that compared polymyxins versus aminoglycosides described no clear differences
      between groups in the proportion of participants with P aeruginosa eradication
      (OR 1.40. 95% CI 0.36 to 5.35; very low-quality evidence) or improvement in
      sputum purulence (OR 0.16, 95% CI 0.01 to 3.85; very low-quality evidence). The
      evidence for changes in FEV1 was inconclusive. Two of three trials reported
      adverse events but did not report the proportion of participants experiencing one
      or more adverse events, so we were unable to interpret the information. AUTHORS'
      CONCLUSIONS: Limited low-quality evidence favours short-term oral
      fluoroquinolones over beta-lactam antibiotics for patients hospitalised with
      exacerbations. Very low-quality evidence suggests no benefit from inhaled
      aminoglycosides verus polymyxins. RCTs have presented no evidence comparing other
      modes of delivery for each of these comparisons, and no RCTs have included
      children. Overall, current evidence from a limited number of head-to-head trials
      in adults or children with bronchiectasis is insufficient to guide the selection
      of antibiotics for short-term or long-term therapy. More research on this topic
      is needed.

PMID- 30184245
TI  - Pseudocnidae of archinemerteans (Nemertea, Palaeonemertea) and their implications
      for nemertean systematics.
AB  - The structure of pseudocnidae of 16 species of Palaeonemertea clade Archinemertea
      (= Cephalotrichida s.l.) was investigated with confocal laser, scanning, and
      transmission electron microscopy (TEM). All species of the genus Cephalothrix
      possess two kinds of pseudocnidae, large and small. Only one type of pseudocnida
      is present in Balionemertes and Cephalotrichella. TEM revealed variation in the
      ultrastructure of large and small pseudocnidae of four species of Cephalothrix.
      Pseudocnidae of Balionemertes, Cephalotrichella, and Cephalothrix differ in
      substructure: in Balionemertes and Cephalotrichella the medulla is located in the
      basal half of the pseudocnidae with a precore layer situated in the apical half,
      whereas in Cephalothrix spp. and other palaeonemerteans the medulla surrounds a
      precore layer. Our results confirm the division of archinemerteans into
      Cephalotrichidae (with genus Cephalothrix) and Cephalotrichellidae (with genera
      Cephalotrichella and Balionemertes). The synapomorphy of Cephalotrichidae is
      pseudocnida dimorphism and the synapomorphies of Cephalotrichellidae are the
      position of the pseudocnidae on epithelial ridges and the distinct organization
      of pseudocnida layers, specifically the relative position of the medulla and
      precore layers. The pseudocnida lateral process, one or more of which is present
      in most species observed, is a probable synapomorphy of the clade Archinemertea.
      This is the first application of pseudocnida features to distinguish super
      generic nemertean taxa and the results suggest that pseudocnidae provide a useful
      source of characters for nemertean systematics.

PMID- 30184244
TI  - WITHDRAWN: Topical and systemic antifungal therapy for the symptomatic treatment
      of chronic rhinosinusitis.
AB  - BACKGROUND: Chronic rhinosinusitis (CRS) is an inflammatory disorder of the nose
      and sinuses. Since fungi were postulated as a potential cause of CRS in the late
      1990s, there has been increasing controversy about the use of both topical and
      systemic antifungal agents in its management. Although interaction between the
      immune system and fungus has been demonstrated in CRS, this does not necessarily
      imply that fungi are the cause of CRS or that antifungals will be effective its
      management. OBJECTIVES: To assess the effectiveness of topical or systemic
      antifungal therapy in the treatment of CRS. SEARCH METHODS: We searched the
      Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane
      Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; CINAHL; Web of
      Science; BIOSIS Previews; Cambridge Scientific Abstracts; ICTRP and additional
      sources for published and unpublished trials. The date of the most recent search
      was 8 March 2011. SELECTION CRITERIA: All randomised, placebo-controlled trials
      considering the use of topical or systemic antifungal therapy in the treatment of
      CRS and allergic fungal sinusitis (AFS). CRS was defined using either the
      European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) or American
      Academy of Otolaryngology - Head and Neck Surgery (AAO-HNS) criteria. DATA
      COLLECTION AND ANALYSIS: We reviewed the titles and abstracts of all studies
      obtained from the searches and selected trials that met the eligibility criteria.
      We extracted data using a pre-determined data extraction form. There was
      significant heterogeneity of outcome data reporting with reports containing both
      parametric and non-parametric representations of data for the same outcomes.
      Means and standard deviations for change data were unavailable for a number of
      trials. Due to the limited reported data, we contacted authors and used original
      data for data analysis. MAIN RESULTS: Six studies were included (380
      participants). Five studies investigated topical antifungals and one study
      investigated systemic antifungals. The risk of bias in all included studies was
      low, with all trials being double-blinded and randomised. Pooled meta-analysis
      showed no statistically significant benefit of topical or systemic antifungals
      over placebo for any outcome. Symptom scores in fact statistically favoured the
      placebo group. Adverse event reporting was statistically significantly higher in
      the antifungal group. AUTHORS' CONCLUSIONS: On the basis of this meta-analysis,
      there is no evidence to support the use of either topical or systemic antifungal
      treatment in the management of CRS.

PMID- 30184246
TI  - Rituximab, bendamustine and cytarabine (R-BAC) in patients with relapsed
      refractory aggressive B-cell lymphoma.

PMID- 30184247
TI  - The ontogenetic scaling of form and function in the spotted ratfish, Hydrolagus
      colliei (Chondrichthyes: Chimaeriformes): Fins, muscles, and locomotion.
AB  - The alteration of form and function through the life of a fish can have profound
      impacts on the ability to move through water. Although several studies have
      examined morphology and function in relation to body size, there is a paucity of
      data for chondrichthyans, an ancient group of fishes. Ratfishes are interesting
      in that they utilize flapping pectoral fins to drive movement, and they diverged
      from elasmobranchs early in the gnathostome phylogeny. Using the spotted ratfish,
      Hydrolagus colliei, we quantified the scaling of traits relevant for locomotion,
      including median and paired fin external anatomy, the musculature of the pectoral
      and pelvic fins, and the kinematics of the pectoral fins. Whereas pelvic fins
      scaled with either positive allometry (fin span and area) or isometry (fin chord
      length at the base of the fin), pectoral fin measurements either scaled with
      negative allometry (fin span and aspect ratio) or isometry (fin area and chord
      length). Correspondingly, all pelvic fin muscles exhibited positive allometry,
      whereas pectoral muscles exhibited a mix of isometric and positively allometric
      growth. Caudal fin area and body frontal area both scaled with positive
      allometry, whereas dorsal fin area and span scale with isometry. Pectoral fin
      amplitude during swimming exhibited isometry, and fin beat frequency decreased
      with body size. Our results highlight the complex changes in form and function
      throughout ontogeny. Finally, we highlight that hierarchical differentiation in
      morphology can occur during growth, potentially leading to complex changes in
      performance of a functional system.

PMID- 30184248
TI  - Flesh and bone: An integrative approach towards sexual size dimorphism of a
      terrestrial salamander (genus Salamandrina).
AB  - Males and females face different selection pressures due to a sexually biased
      investment into reproduction. This often results in different morphologies.
      Sexual size dimorphisms (SSD) can give us important hints on the evolution and
      biology of a species. Salamanders are a perfectly suited system for investigating
      SSD, including a diversity of reproductive modes and behaviors, and patterns of
      SSD combined with life history traits in a phylogenetic context help us to
      understand the evolution of these processes. Because spectacled salamanders
      (genus Salamandrina) are the phylogenetically most basal taxon of the
      Salamandridae, they play a key role in reconstructing the evolutionary pattern of
      SSD. Combining extensive external and skeletal measurements of the cranium,
      limbs, and the pelvic girdle using high-resolution micro Computer Tomography
      (MUCT) yielded an integrative analysis of expressed SSD of morphology and
      osteology of Salamandrina perspicillata. Multivariate analysis of external
      characters showed that males generally had larger cloacae, heads, and limbs
      relative to body size, while females had larger trunks. Analysis of osteology
      confirmed this pattern but also revealed new dimorphic characters in the cranium
      and the pelvic girdle. Dimorphic characters in external morphology and osteology
      are likely linked to the different reproductive roles of the sexes and support
      sexual rather than ecological selection as the primary force acting on the
      phenotype of the phylogenetically basal salamandrids.

PMID- 30184249
TI  - Enrolled nurses' experiences of caring for patients living with HIV in a South
      African rural hospital.
AB  - BACKGROUND: Most public hospitals in African countries are overpopulated with
      patients suffering from conditions related to HIV and AIDS. These patients
      increase the burden on healthcare providers, among which are enrolled nurses.
      AIM: To explore enrolled nurses' experiences of caring for patients living with
      HIV and AIDS at a public rural community hospital in the Vhembe district of
      Limpopo Province, South Africa. DESIGN: The study was underpinned by the
      interpretative phenomenological design. PARTICIPANTS: A total of 11 purposively
      selected enrolled nurses who met the inclusion criteria participated in the
      study. The sample size was based on data saturation. METHOD: Data were collected
      through semi-structured individual face-to-face interviews guided by an interview
      guide. Interviews were audio-recorded; and field notes were also taken. Data were
      analysed thematically following a framework for interpretative phenomenological
      analysis. RESULTS: The study revealed that enrolled nurses are working without
      adequate resources. They also experience minimal support despite the negative
      circumstances they are exposed to in the process of caring for patients admitted
      with HIV-related illnesses. CONCLUSIONS: A lack of resources, limited support and
      inadequate skills have a negative impact on the health care that enrolled nurses
      provide to patients admitted in hospital with HIV-related ailments. Researchers
      recommend the importance of supporting and equipping enrolled nurses to provide
      quality care to patients living with HIV. IMPLICATIONS FOR NURSING AND HEALTH
      POLICY: The findings have highlighted the challenges faced by enrolled nurses
      while caring for patients with HIV. The identified gaps will assist the
      Department of Health in developing policies to enhance the support offered to
      enrolled nurses and improve the care provided to patients with HIV-related
      conditions that are admitted to rural hospitals.

PMID- 30184250
TI  - Effects of Maillard Reaction Products on Sensory and Nutritional Qualities of the
      Traditional French Baguette.
AB  - : The goals of this study were to evaluate the effect of baking time on the
      Maillard reaction products (MRPs) generated in the crust of the traditional
      French baguette and to estimate their impact on its sensory characteristics, its
      acrylamide content, and its bifidogenic effect. Melanoidins, volatile compounds,
      and acrylamide were evaluated in the crust of traditional French baguettes baked
      between 12 and 22 min at 225  degrees C. The increase in melanoidins was
      positively correlated to the baking time, while volatile compounds only increased
      until 18 min. The acrylamide content was estimated to be below 18 MUg/kg, which
      confirms the findings of EFSA that bread is not a main contributor to dietary
      acrylamide. A descriptive sensory analysis showed that the baking time positively
      affected the sensory quality of the crust. The consumer test revealed the same
      trend and the panelists favorably judged the well-baked baguettes based on a
      better crust flavor and crispness. The bifidogenic effect of the crust and the
      crumb from the baguettes baked 22 min was evaluated on the in vitro growth of
      Bifidobacterium adolescentis. The results demonstrated that the crumb and the
      crust had exactly the same bifidogenic impact, therefore not caused by
      melanoidins. PRACTICAL APPLICATION: The consumption of bread in France has
      decreased since 2007, although bread is considered by French people as "healthy"
      and essential to maintain a balanced diet. The current study evaluated the global
      qualities of the French baguette in order to highlight its high sensory quality
      and its beneficial effect by inducing a possible growth of bifidobacteria, even
      in well-baked baguettes. These findings allow the French bakery industry to
      develop an argument to promote its technical know-how and to help consumers
      choose healthier and tastier bread. Moreover, this study provided some
      recommendations of baking processes to maintain a high sensory quality of the
      French baguette and limit the formation of undesirable compounds, such as
      acrylamide, in the crust.

PMID- 30184251
TI  - Acceptability of Peanut Skins as a Natural Antioxidant in Flavored Coated
      Peanuts.
AB  - : Peanut skins are a low-value byproduct of the peanut processing industry.
      Following their removal during the preparation of common peanut products, they
      are either discarded or used as a minor component of animal feed. Studies have
      found peanuts skins to be rich in health promoting phenolic compounds and thus
      have potential as a functional food ingredient. The aim of this study was to
      evaluate a new product that included the encapsulated phenolic extract from
      peanut skins in a flavored coating for peanuts. The phenolic compounds were
      extracted from peanut skins and then encapsulated in 10.5% (w/w) maltodextrin in
      to reduce the bitter flavor. The encapsulated phenolic extract was added at
      varying concentrations to honey roast flavored and chili lime flavored coatings
      which were applied to roasted peanuts. The resulting total phenolic content and
      antioxidant potential of the coated peanuts were evaluated by the Folin
      Ciocalteu, DPPH, and beta-carotene bleaching assays. A best estimate sensory
      threshold for the peanut skin extract in the honey roasted and chili lime coating
      was found to be 12.8% (w/w) and 16.6% (w/w), respectively. The total phenolic
      content and antioxidant capacity for both the honey roasted and chili lime coated
      peanuts at their threshold was found to be significantly higher than control
      peanuts that did not contain peanut skins in the coating. The increased
      antioxidant activity and unaltered flavor profile at the sensory threshold levels
      of peanut skins demonstrated their potential as a functional food ingredient.
      PRACTICAL APPLICATION: The ability of polyphenols to act as antioxidants suggests
      that extracts of peanut skins containing polyphenols can be used as functional
      ingredients in new food products. The encapsulation of peanut skin extract in
      maltodextrin allowed for the incorporation of the extracts into flavored coatings
      for peanuts at levels high enough to increase the antioxidant activity without
      impacting sensory profiles. Utilization of this by-product of the peanut can
      create an economic opportunity for the peanut industry.

PMID- 30184252
TI  - Fc gamma receptor IIa suppresses type I and III interferon production by human
      myeloid immune cells.
AB  - Type I and type III interferons (IFNs) are fundamental for antiviral immunity,
      but prolonged expression is also detrimental to the host. Therefore, upon viral
      infection high levels of type I and III IFNs are followed by a strong and rapid
      decline. However, the mechanisms responsible for this suppression are still
      largely unknown. Here, we show that IgG opsonization of model viruses influenza
      and respiratory syncytial virus (RSV) strongly and selectively suppressed type I
      and III IFN production by various human antigen-presenting cells. This
      suppression was induced by selective inhibition of TLR, RIG-I-like receptor, and
      STING-dependent type I and III IFN gene transcription. Surprisingly, type I and
      III IFN suppression was mediated by Syk and PI3K independent inhibitory signaling
      via FcgammaRIIa, thereby identifying a novel non-canonical FcgammaRIIa pathway in
      myeloid cells. Together, these results indicate that IgG opsonization of viruses
      functions as a novel negative feedback mechanism in humans, which may play a role
      in the selective suppression of type I and III IFN responses during the late
      phase of viral infections. In addition, activation of this pathway may be used as
      a tool to limit type I IFN-associated pathology.

PMID- 30184253
TI  - Consumer Acceptance, Emotional Response, and Purchase Intent of Rib-Eye Steaks
      from Grass-Fed Steers, and Effects of Health Benefit Information on Consumer
      Perception.
AB  - : Sensory acceptability, purchase intent (PI), consumer emotional profile, and
      fatty acid profile of rib-eye steaks from four different biological types of
      grass-fed cattle (Angus, Brangus, Pineywoods, and Holstein) were evaluated. The
      effects of health benefit information (HBI) pertaining to grass-fed beef on the
      overall liking (OL), emotional profile, and PI were also studied. Consumers rated
      steaks from the two nontraditional beef biological types (Pineywoods and
      Holstein) equally or higher than conventional biological types (Angus and
      Brangus) in several hedonic (9-point scale) categories. Mean OL scores were 6.1
      for Pineywoods and 6.3 for Holstein steaks, versus 5.5 for Angus and 6.0 for
      Brangus. Hedonic attributes, especially OL and liking of beef flavor, accounted
      for most of the differences between treatments based on Wilks' Lambda
      Multivariate Analysis of Variance (MANOVA) and descriptive discriminant analysis.
      After knowledge of HBI, OL of all treatments increased, particularly Angus with
      OL mean score significantly increasing from 5.5 to 6.2. Positive PI increased
      significantly for Angus (from 48% to 65.33%), Brangus (from 50.67% to 66.67%),
      and Holstein (from 61.33% to 76%) steaks. Angus steaks, which initially received
      the lowest beef flavor liking (5.1) showed the most improvement for OL after HBI.
      Likewise, emotional profiles were improved after HBI, particularly the
      "Interested" emotion with a 0.5 unit increased. PRACTICAL APPLICATION: Providing
      consumers with health benefit information (HBI) can enhance acceptability of
      grass-fed beef. Fatty acid analyses of steaks from four biological types of
      steers showed favorable n-6/n-3 ratios. Although some sensory attributes of
      cooked rib-eye steaks were scored differently among biological types, knowledge
      of grass-feeding and healthier fatty acids increased overall liking and purchase
      intent (PI) across products. Emotional profiles improved after HBI was given to
      consumers, with some emotions being significantly related to PI odds ratios. This
      research demonstrated the usefulness of HBI in improving hedonic perceptions of
      grass-fed steaks and the importance of consumer emotions in predicting PI.

PMID- 30184254
TI  - Volume of ropivacaine 0.2% and common peroneal nerve block duration: a
      randomised, double-blind cohort trial in healthy volunteers.
AB  - The volume-duration relationship using low concentrations of ropivacaine for
      peripheral nerve blocks is unknown, even though low concentrations of ropivacaine
      are increasingly used clinically. We investigated the effect of ropivacaine 0.2%
      on common peroneal nerve block duration. With ethical committee approval, 60
      consenting, healthy volunteers were randomly allocated to receive one of five
      volumes of ropivacaine 0.2% (2.5, 5.0, 10, 15 or 20 ml) administered by
      ultrasound-guided, catheter-based injection (at 10 ml.min-1 ) near the common
      peroneal nerve. Our primary outcome was duration of sensory block, defined by
      insensitivity to a cold stimulus. Our secondary outcome was duration of motor
      block. Outcomes were assessed every hour from onset of block to complete
      remission. Intergroup differences were tested using one-way ANOVA followed by
      regression analyses using the 20 ml intervention group as reference. Block
      durations varied significantly (p < 0.0001) between groups. Mean (SD) sensory
      block durations were 9.2 (3.3), 12.5 (3.0), 15.5 (4.4), 17.3 (3.5) and 17.3 (4.6)
      h. Mean (SD) motor block durations were 3.3 (2.1), 7.2 (2.5), 9.2 (2.2), 12.7
      (2.5) and 12.5 (2.5) h. Regression analysis showed that the effect of volume on
      block duration was progressively smaller with increasing volume, reaching a
      threshold volume above which there was no effect on nerve block duration (10 ml
      for sensory block and 15 ml for motor block). We conclude that there is a ceiling
      effect of increasing volume of ropivacaine 0.2% on both sensory and motor block
      duration of the common peroneal nerve.

PMID- 30184255
TI  - Multiple circadian clock outputs regulate diel turnover of carbon and nitrogen
      reserves.
AB  - Plants accumulate reserves in the daytime to support growth at night. Circadian
      regulation of diel reserve turnover was investigated by profiling starch, sugars,
      glucose 6-phosphate, organic acids and amino acids during a light-dark cycle and
      after transfer to continuous light in Arabidopsis wild-types and in mutants
      lacking dawn (lhy cca1), morning (prr7 prr9), dusk (toc1, gi) or evening (elf3)
      clock components. The metabolite time-series were integrated with published time
      series for circadian clock transcripts to identify circadian outputs that
      regulate central metabolism. i) Starch accumulation was slower in elf3 and prr7
      prr9. It is proposed that ELF3 positively regulates starch accumulation. ii)
      Reducing sugars were high early in the T-cycle in elf3, revealing that ELF3
      negatively regulates sucrose recycling. iii) The pattern of starch mobilization
      was modified in all five mutants. A model is proposed in which dawn and
      dusk/evening components interact to pace degradation to anticipated dawn. iv) An
      endogenous oscillation of glucose 6-phosphate revealed that the clock buffers
      metabolism against the large influx of carbon from photosynthesis. v) Low levels
      of organic and amino acids in lhy cca1 and high levels in prr7 prr9 provide
      evidence that the dawn components positively regulate the accumulation of amino
      acid reserves.

PMID- 30184256
TI  - Airway epithelial TSLP production of TLR2 drives type 2 immunity in allergic
      airway inflammation.
AB  - Epithelial cells (ECs)-derived cytokines are induced by different stimuli through
      pattern recognition receptors (PRRs) to mount a type-2-cell-mediated immune
      response; however, the underlying mechanisms are poorly characterized. Here, we
      demonstrated asthmatic features in both primary bronchial epithelial cells
      (pBECs) and mouse model using several allergens including ovalbumin (OVA), house
      dust mite (HDM), or Alternaria alternata. We found that toll-like receptor 2
      (TLR2) was highly induced in ECs but not dendritic cells (DCs) by various
      allergens, leading to recruitment of circulating basophils into the lung via C-C
      chemokine ligand-2 (CCL2). TLR2 expression increased thymic stromal lymphopoietin
      (TSLP) production through the NF-kappaB and JNK signaling pathways to extend the
      survival of recruited basophils and resident DCs in the lung, predisposing a type
      2-cell-mediated airway inflammation. Conversely, TLR2 deficiency impaired
      secretion of TSLP and CCL2, decreased infiltration of lung basophils, and
      increased resistance to Th2 response. Blocking TSLP also phenocopied these
      phenomena. Our findings reveal a pro-inflammatory role of airway ECs through a
      TLR2-dependent TSLP production, which may have implication for treating allergic
      asthma.

PMID- 30184257
TI  - Centrifugation-free washing reduces buildup of potassium and free hemoglobin in
      washed red blood cells after the procedure.

PMID- 30184258
TI  - A difficult case of beta-catenin-mutated hepatocellular adenoma: a lesson for
      diagnosis.

PMID- 30184259
TI  - Reversal of albuminuria by combined AM6545 and perindopril therapy in
      experimental diabetic nephropathy.
AB  - BACKGROUND AND PURPOSE: The endocannabinoid (EC) system has been implicated in
      the pathogenesis of diabetic nephropathy (DN). We investigated the effects of
      peripheral blockade of the cannabinoid CB1 receptor as an add-on treatment to ACE
      inhibition in type 1 diabetic mice (DM) with established albuminuria.
      EXPERIMENTAL APPROACH: Renal functional parameters (albumin excretion rate,
      creatinine clearance), tubular injury, renal structure, both EC and CB receptor
      levels and markers of podocyte dysfunction, fibrosis and inflammation were
      studied in streptozotocin-induced DM treated for 14 weeks with vehicle, the ACE
      inhibitor perindopril (2 mg.kg-1 .day-1 ), peripherally-restricted CB1 receptor
      antagonist AM6545 (10 mg.kg-1 .day-1 ) or both. Treatments began at 8 weeks after
      diabetes onset, when early DN is established. KEY RESULTS: CB1 receptors were
      overexpressed in DM and neither perindopril nor AM6545 altered this effect, while
      both drugs abolished diabetes-induced overexpression of angiotensin AT1
      receptors. Single treatment with either AM6545 or perindopril significantly
      reduced progression of albuminuria, down-regulation of nephrin and podocin,
      inflammation and expression of markers of fibrosis. However, reversal of
      albuminuria was only observed in mice administered both treatments. The ability
      of the combination therapy to completely abolish slit diaphragm protein loss,
      monocyte infiltration, overexpression of inflammatory markers and favour
      macrophage polarization towards an M2 phenotype may explain this greater
      efficacy. In vitro experiments confirmed that CB1 receptor activation directly
      inhibits retinoic acid-induced nephrin expression in podocytes and IL-4-induced
      M2 polarization in macrophages. CONCLUSION AND IMPLICATIONS: Peripheral CB1
      receptor blockade used as add-on treatment to ACE-inhibition reverses
      albuminuria, nephrin loss and inflammation in DM.

PMID- 30184261
TI  - Neonatal TSH levels in Northern Ireland from 2003 to 2014 as a measure of
      population iodine status.
AB  - OBJECTIVE: The re-emergence of iodine deficiency in the UK has recently been
      reported in a large cohort of teenage girls including from Northern Ireland (NI)
      using the gold standard spot urinary iodine concentration. We wished to explore
      and confirm this by analysing neonatal thyroid-stimulating hormone (nTSH) levels
      in the NI population. DESIGN: We analysed the nTSH heel prick tests results from
      the NI national screening database between 2003 and 2014. The WHO proposes a
      definition for population iodine sufficiency at <3% of the population with nTSH
      results >5 mIU/L. METHODS: Anonymized results from 288 491 nTSH tests were
      retrieved, and prevalence rates of results at increasing cut-offs including >2
      mIU/L and >5 mIU/L calculated. We also assessed for possible seasonal variation
      in nTSH results. RESULTS: An overall population prevalence of 0.49% with TSH >5
      mIU/L was found, indicating population iodine sufficiency with no year attaining
      a prevalence >3%. The prevalence of nTSH >2 mIU/L decreased to 4.1% in 2007 and
      subsequently increased to 9.8% in 2014. Modest seasonal variation was also
      detected, with higher levels among April/May births. CONCLUSIONS: The neonatal
      TSH database suggests iodine sufficiency in the NI population. However, the
      rising frequency of results >2 mIU/L may indicate an emerging mild iodine
      deficiency. This is one of the largest and longest studies of its kind in the UK
      and the first carried out in NI. The summer months may be a time of increased
      risk of iodine deficiency in our pregnant women whose requirements are increased
      and who are not currently targeted by any iodine fortification programme in the
      UK.

PMID- 30184262
TI  - A modified temporary tracheostomy in dogs: outcome and complications in 21 dogs
      (2012 to 2017).
AB  - OBJECTIVES: To describe a modified temporary tracheostomy that included placing a
      Penrose drain sling dorsal to the trachea. To report outcomes and complications
      in brachycephalic versus non-brachycephalic breeds. MATERIALS AND METHODS:
      Retrospective review of signalment, diagnosis, outcome, complications and
      management of dogs that underwent modified temporary tracheostomy. RESULTS:
      Twenty-one dogs were included. Tracheostomy tubes were maintained for periods
      ranging from 1 to 21 days (median 4 days). There were no intraoperative
      complications or complications related to the placement of the Penrose drain.
      Postoperative complications occurred in eight dogs, including dislodgement of the
      tracheostomy tube (n=6), obstruction of the tracheostomy tube (n=1), subcutaneous
      emphysema and pneumomediastinum (n=1). Twenty dogs survived until discharge; one
      was euthanised due to persistence of primary disease. The complication rate in
      brachycephalic breeds and non-brachycephalic was 37?5 and 40%, respectively. Tube
      dwell duration of 4 days or longer was associated with a higher complication
      rate. CLINICAL SIGNIFICANCE: The modified temporary tracheostomy appears to
      simplify tracheostomy care, improve tracheostomy outcome and reduce tube
      associated mortality compared with standard tracheostomy. In this study,
      brachycephalic dogs did not have a higher complication rate than non
      brachycephalic dogs.

PMID- 30184260
TI  - Immunomodulatory tetracyclines shape the intestinal inflammatory response
      inducing mucosal healing and resolution.
AB  - BACKGROUND AND PURPOSE: Immunomodulatory tetracyclines are well-characterized
      drugs with a pharmacological potential beyond their antibiotic properties.
      Specifically, minocycline and doxycycline have shown beneficial effects in
      experimental colitis, although pro-inflammatory actions have also been described
      in macrophages. Therefore, we aimed to characterize the mechanism behind their
      effect in acute intestinal inflammation. EXPERIMENTAL APPROACH: A comparative
      pharmacological study was initially used to elucidate the most relevant actions
      of immunomodulatory tetracyclines: doxycycline, minocycline and tigecycline;
      other antibiotic or immunomodulatory drugs were assessed in bone marrow-derived
      macrophages and in dextran sodium sulfate (DSS)-induced mouse colitis, where
      different barrier markers, inflammatory mediators, microRNAs, TLRs, and the gut
      microbiota composition were evaluated. The sequential immune events that mediate
      the intestinal anti-inflammatory effect of minocycline in DSS-colitis were then
      characterized. KEY RESULTS: Novel immunomodulatory activity of tetracyclines was
      identifed; they potentiated the innate immune response and enhanced resolution of
      inflammation. This is also the first report describing the intestinal anti
      inflammatory effect of tigecycline. A minor therapeutic benefit seems to derive
      from their antibiotic properties. Conversely, immunomodulatory tetracyclines
      potentiated macrophage cytokine release in vitro, and while improving mucosal
      recovery in colitic mice, they up-regulated Ccl2, miR-142, miR-375 and Tlr4. In
      particular, minocycline initially enhanced IL-1beta, IL-6, IL-22, GM-CSF and IL-4
      colonic production and monocyte recruitment to the intestine, subsequently
      increasing Ly6C- MHCII+ macrophages, Tregs and type 2 intestinal immune
      responses. CONCLUSIONS AND IMPLICATIONS: Immunomodulatory tetracyclines
      potentiate protective immune pathways leading to mucosal healing and resolution,
      representing a promising drug reposition strategy for the treatment of intestinal
      inflammation.

PMID- 30184264
TI  - Prenatal and preimplantation genetic diagnosis for single gene disorders: A
      population-based study from 1977 to 2016.
AB  - OBJECTIVE: To examine the statewide utilisation of prenatal diagnosis (PNDx) and
      preimplantation genetic diagnosis (PGT-M) for single gene disorders. METHODS:
      Population-based study of all women utilising PNDx in the Australian state of
      Victoria from 1977 to 2016. Single gene disorders were categorised using a
      systematic approach that aimed to reflect aspects of the PNDx decision-making
      process. Data on PGT-M for single gene disorders from 2005 to 2016 were similarly
      examined for comparison. Statistical significance testing was performed with chi2
      test. RESULTS: Following an initial uptake period, annual PNDx rates for single
      gene disorders stabilised between 1.3 and 2.2 per 1000 births after the year
      2000. The majority of PNDx (72%) was performed for disorders that primarily
      impair physical ability, while PNDx for adult onset conditions was rare (3%). PGT
      M for single gene disorders has seen rapid growth since its introduction, and
      annual numbers now equal that of PNDx. In contrast to PNDx, one quarter of PGT-M
      tests were performed for adult onset conditions. CONCLUSIONS: Our population-wide
      analysis has demonstrated a steady demand for PNDx for single gene disorders over
      the past decade, in contrast to the rapidly increasing utilisation of PGT-M. PGT
      M appears to be the preferred testing modality for adult onset disorders.

PMID- 30184265
TI  - The Challenges of DNA Extraction in Different Assorted Food Matrices: A Review.
AB  - High-quality DNA extracts are imperative for downstream applications in molecular
      identification. Most processed food products undergo heat treatments causing DNA
      degradation, which hampers application of DNA-based techniques for food
      authentication. Moreover, the presence of inhibitors in processed food products
      is also problematic, as inhibitors can impede the process of obtaining high
      qualities and quantities of DNA. Various approaches in DNA extraction and factors
      in structure and texture of various food matrices affecting DNA extraction are
      explained in this review.

PMID- 30184266
TI  - Perception of parents/caregivers on the oral health of children/adolescents with
      Down syndrome.
AB  - INTRODUCTION: Oral health affects the general health of people with Down syndrome
      (DS), with repercussions on their ability to chew and to communicate. OBJECTIVE:
      To evaluate the influence of sociodemographic characteristics and clinical
      indicators on the perceptions of parents/caregivers regarding the oral health of
      individuals with DS. METHODS: Parents/caregivers completed a questionnaire
      containing sociodemographic information and answered the 20 questions of the
      Brazilian version of the Oral Health Scale for People with DS. Intra-oral
      clinical exam of children/adolescents was performed to assess dental caries,
      periodontal disease, and malocclusion. Descriptive statistics, bivariate
      analyses, and Poisson regression model analyses were carried out. RESULTS: In
      this study, 55.1% of the parents/caregivers showed a positive perception
      regarding the oral health of their children/adolescents. Parents/caregivers of
      individuals between 4 and 9 years old (Prevalence Ratio (PR) = 1.13; Confidence
      Interval (CI), 1.04 - 1.23; p = 0.003) and parents/caregivers of those with
      definite malocclusion (PR = 1.14; CI, 1.00 - 1.31; p = 0.047) had a higher
      prevalence of reporting a more negative perception of their
      children's/adolescents' oral health. CONCLUSION: DS individuals' age and the
      severity of malocclusion were indicators of a more negative perception of
      parents/caregivers regarding their sons'/daughters' oral health.

PMID- 30184263
TI  - NAD+ promotes assembly of the active tetramer of aldehyde dehydrogenase 7A1.
AB  - Nicotinamide adenine dinucleotide (NAD) is the redox cofactor of many enzymes,
      including the vast aldehyde dehydrogenase (ALDH) superfamily. Although the
      function of NAD(H) in hydride transfer is established, its influence on protein
      structure is less understood. Herein, we show that NAD+ -binding promotes
      assembly of the ALDH7A1 tetramer. Multiangle light scattering, small-angle X-ray
      scattering, and sedimentation velocity all show a pronounced shift of the dimer
      tetramer equilibrium toward the tetramer when NAD+ is present. Furthermore,
      electron microscopy shows that cofactor binding enhances tetramer formation even
      at the low enzyme concentration used in activity assays, suggesting the tetramer
      is the active species. Altogether, our results suggest that the catalytically
      active oligomer of ALDH7A1 is assembled on demand in response to cofactor
      availability.

PMID- 30184267
TI  - Estimating Renal Function in Drug Development: Time to Take the Fork in the Road.
AB  - Renal function is the most commonly applied patient-specific quantitative
      variable used to determine drug doses. Measurement of renal function is not
      practical in most clinical settings; therefore, clinicians often rely on
      estimates when making dosing decisions. Similarly, renal function estimates are
      used to assign subjects in phase 1 pharmacokinetic studies, which inform dosing
      in late-phase clinical trials and ultimately the product label. The Cockcroft
      Gault estimate of creatinine clearance has been the standard renal function
      metric; however, this paradigm is shifting toward the Modification of Diet in
      Renal Diseases (MDRD) estimate of the glomerular filtration rate (GFR). The
      proportion of approved new drug labels with dosing recommendations based on the
      MDRD equation was 16.7% in 2015, 70.0% in 2016, and 46.7% in 2017. Disharmonious
      recommendations from the United States Food and Drug Administration and the
      European Medicines Agency will continue to increase this heterogeneity in the
      assessment of renal function in drug development and negatively impact industry,
      health systems, and clinicians. In this review, we discuss the current regulatory
      guidance for the conduct of renal impairment pharmacokinetic studies and review
      the implications of this guidance across the medication use system with 3
      recently approved antibiotics: ceftazidime/avibactam, delafloxacin, and
      meropenem/vaborbactam. Finally, we suggest measuring GFR in phase 1 studies and
      employing the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
      equation to integrate data across clinical trials. This will help to harmonize
      CKD staging, population pharmacokinetic analyses, and dosing by estimated renal
      function.

PMID- 30184268
TI  - Content of Selected Vitamins and Antioxidants in Colored and Nonpigmented
      Varieties of Quinoa, Barley, and Wheat Grains.
AB  - : The diversity in human diets that can be reached by proper use of different
      crops and varieties, including some underutilized ones, is a potentially powerful
      strategy to ensure food security and prevent serious health problems caused by
      current diets that are often not fulfilling nutritional requirements. In the
      framework of this research, the content of tocopherols and tocotrienols,
      thiamine, riboflavin, pyridoxine, and superoxide dismutase in nine varieties of
      quinoa, both colored and nonpigmented, obtained from 4 different countries, was
      investigated and compared to the content of the same vitamins and antioxidants in
      barley and wheat, both colored and nonpigmented, cultivated in the same
      experimental field. The aim of this work was to create a crop diversity strategy
      and encourage the consumption of underutilized crops to ensure that the human
      diet fulfills nutritional requirements. The contents of vitamin B1, B2, B6,
      tocopherol, and tocotrienol isomers and superoxide dismutase were determined via
      HPLC; imaging techniques were used to evaluate the seed color. Quinoa grains had
      the greatest concentration of tocopherol isomers and activity, represented mainly
      by alpha-tocopherol and gamma-tocopherol. Wheat and barley seeds had substantial
      concentrations of tocopherols and tocotrienols. The concentration of riboflavin
      was greater in barley and wheat than in quinoa, the concentrations of pyridoxine
      and thiamine were variety-dependent in all grains. Quinoa grains had greater
      concentration of superoxide dismutase compared to wheat and barley. The richness
      of each variety and crop should be recognized and used integrally to improve the
      diet quality. PRACTICAL APPLICATION: Nutritional potential of crops was evaluated
      from the viewpoint of selected vitamins and antioxidants to create a well
      balanced diet. Combined use of both traditional (wheat, barley) and underutilized
      crops (quinoa) is recommended. HPLC methods and image analysis were successfully
      used as viable tools for food quality determination.

PMID- 30184269
TI  - Injury-Related Healthcare Use and Risk of Filicide Victimization: A Population
      Based Case-Control Study.
AB  - Research on child-related risk factors for filicide is scant. We investigated
      whether prior healthcare use for injury (including poisoning) influences filicide
      risk. Victims (0-14 years; n = 71) were identified in a national autopsy database
      for the years 1994-2012 and compared to matched, general population controls (n =
      355). Healthcare use data were retrieved from a national patient registry. Risks
      were estimated using odds ratios (ORs) and 95% confidence intervals (CIs). For
      females, prior inpatient care for injury conferred a statistically significant
      sevenfold risk (OR = 6.67 [95% CI: 1.49-29.79]), and any prior injury-related
      healthcare use conferred a statistically significant fourfold risk (OR = 3.57
      [95% CI: 1.13-11.25]), of filicide victimization. No statistically significant
      risks were found for males. Healthcare personnel should be aware that children
      treated for injuries, especially females, may be at an elevated risk of filicide
      victimization. Nevertheless, the filicide base rate remains low, and parents may
      be stigmatized by unfounded alerts; thus, prudent reflection should precede
      reports to the authorities.

PMID- 30184270
TI  - Functional Characterization of a GGPPS Variant Identified in Atypical Femoral
      Fracture Patients and Delineation of the Role of GGPPS in Bone-Relevant Cell
      Types.
AB  - Atypical femoral fractures (AFFs) are a rare but potentially devastating event,
      often but not always linked to bisphosphonate (BP) therapy. The pathogenic
      mechanisms underlying AFFs remain obscure, and there are no tests available that
      might assist in identifying those at high risk of AFF. We previously used exome
      sequencing to explore the genetic background of three sisters with AFFs and three
      additional unrelated AFF cases, all previously treated with BPs. We detected 37
      rare mutations (in 34 genes) shared by the three sisters. Notably, we found a
      p.Asp188Tyr mutation in the enzyme geranylgeranyl pyrophosphate synthase, a
      component of the mevalonate pathway, which is critical to osteoclast function and
      is inhibited by N-BPs. In addition, the CYP1A1 gene, responsible for the
      hydroxylation of 17beta-estradiol, estrone, and vitamin D, was also mutated in
      all three sisters and one unrelated patient. Here we present a detailed list of
      the variants found and report functional analyses of the GGPS1 p.Asp188Tyr
      mutation, which showed a severe reduction in enzyme activity together with
      oligomerization defects. Unlike BP treatment, this genetic mutation will affect
      all cells in the carriers. RNAi knockdown of GGPS1 in osteoblasts produced a
      strong mineralization reduction and a reduced expression of osteocalcin, osterix,
      and RANKL, whereas in osteoclasts, it led to a lower resorption activity. Taken
      together, the impact of the mutated GGPPS and the relevance of the downstream
      effects in bone cells make it a strong candidate for AFF susceptibility. We
      speculate that other genes such as CYP1A1 might be involved in AFF pathogenesis,
      which remains to be functionally proved. The identification of the genetic
      background for AFFs provides new insights for future development of novel risk
      assessment tools. (c) 2018 American Society for Bone and Mineral Research.

PMID- 30184271
TI  - Clinically Relevant Doses of Sclerostin Antibody Do Not Induce Osteonecrosis of
      the Jaw (ONJ) in Rats with Experimental Periodontitis.
AB  - Antiresorptive agents, such as bisphosphonates and denosumab, are frequently used
      for the management of osteoporosis. Indeed, both medications decrease the risk of
      osteoporotic fractures; however, these medications are associated with rare but
      potentially severe side effects, such as osteonecrosis of the jaw (ONJ). ONJ,
      defined as an area of exposed bone in the maxillofacial region that lasts for 8
      weeks, often presents with significant pain and infection and can lead to serious
      complications. Interestingly, other treatments for osteoporosis have been
      developed, such as antibodies against the osteocyte-secreted protein, sclerostin.
      Sclerostin functions to inhibit the Wnt signaling cascade, leading to inhibition
      of bone formation. In clinical trials, a sclerostin antibody (romosozumab, Amgen
      Inc., UCB Brussels) increases bone formation and lowers the risk of osteoporotic
      fractures. However, in conjunction with increased osteoblastic activity, a
      reduction in bone resorption markers is observed. This antiresorptive effect
      raises the concern of possible ONJ development in patients treated with
      sclerostin antibodies. Here, utilizing ligature-induced experimental
      periodontitis (EP), we evaluated the effects of sclerostin inhibition on the
      development of ONJ-like lesions in ovariectomized rats. Beginning 8 weeks post
      ovariectomy, rats were treated for 22 weeks with weekly injections of vehicle
      (Veh), 200 MUg/kg zoledronic acid (ZA), a potent bisphosphonate at 100-fold the
      osteoporosis dose, or 5 mg/kg sclerostin antibody (Scl-Ab) at the osteoporotic
      dose. EP was initiated at week 12 and maintained for the remainder of the study.
      Scl-Ab treatment transiently increased serum P1NP, a bone formation marker,
      increased BV/TV, and decreased eroded surfaces in lumbar vertebrae. ZA-treated
      rats developed histologic features of ONJ, whereas Veh-treated controls did not.
      Scl-Ab animals lost less periodontal bone in sites with EP. However, these
      animals presented with no histologic signs of ONJ. In conclusion, sclerostin
      inhibition enhanced structural bone parameters, without inducing ONJ-like
      lesions, in ovariectomized rats with EP. (c) 2018 American Society for Bone and
      Mineral Research.

PMID- 30184272
TI  - Factors associated with the increased bleeding in the postoperative period of
      cardiac surgery: A cohort study.
AB  - AIMS AND OBJECTIVES: To identify factors associated with the increased bleeding
      in patients during the postoperative period after cardiac surgery. BACKGROUND:
      Bleeding is among the most frequent complications that occur in the postoperative
      period after cardiac surgery, representing one of the major factors in morbidity
      and mortality. Understanding the factors associated with the increased bleeding
      may allow nurses to anticipate and prioritise care, thus reducing the mortality
      associated with this complication. DESIGN: Prospective cohort study. METHODS:
      Adult patients in a cardiac hospital who were in the postoperative period
      following cardiac surgery were included. Factors associated with the increased
      bleeding were investigated by means of linear regression, considering time
      intervals of 6 and 12 hr. RESULTS: The sample comprised 391 participants. The
      factors associated with the increased bleeding in the first 6 hr were male sex,
      body mass index, cardiopulmonary bypass duration, anoxia duration, metabolic
      acidosis, higher heart rate, platelets and the activated partial thromboplastin
      time in the postoperative period. Predictors in the first 12 hr were body mass
      index, cardiopulmonary bypass duration, metabolic acidosis, higher heart rate,
      platelets and the activated partial thromboplastin time in the postoperative.
      CONCLUSIONS: This study identified factors associated with the increased
      postoperative bleeding from cardiac surgery that have not been reported in
      previous studies. The nurse is important in the vigilance, evaluation and
      registry of chest tube drainage and modifiable factors associated with the
      increased bleeding, such as metabolic acidosis and postoperative heart rate, and
      in discussions with the multiprofessional team. RELEVANCE TO CLINICAL PRACTICE:
      Knowledge of the factors associated with the increased bleeding is critical for
      nurses so they can provide prophylactic interventions and early postoperative
      treatment when needed.

PMID- 30184273
TI  - A narrative analysis of the stories of mothers who have parented a child with
      Hodgkin lymphoma who is currently in early survivorship.
AB  - AIMS AND OBJECTIVES: To explore the lived experience of mothers of children who
      have survived Hodgkin lymphoma, from diagnosis, through treatment and recovery as
      she has lived it and in her own words and to discuss the self-reported
      experiences in the context of the theoretical propositions of Attachment Theory
      and birth order as it applies to the mother-child dyad with this life experience.
      BACKGROUND: While much has been written about childhood cancer survivors and
      their parents independently, there are unique struggles that a mother and a
      childhood cancer survivor face as a dyad. Examining the dyadic relationship over
      time offers a unique perspective to understanding the parenting experience with a
      child whose fate is uncertain. DESIGN AND METHOD: Narrative Inquiry was utilised
      to explore the bonds the mother has with her child before he or she is diagnosed
      with cancer, the relationship during treatment and the subsequent relationship
      when the child has entered survivorship. Most specifically, the research explored
      the attachment of the mother to her child as it relates to the Caregiving System.
      A purposive sample of 13 mothers of children diagnosed with Hodgkin lymphoma
      representing children from each birth order category (youngest child, middle
      child, oldest child and only child) was chosen. The interviews were analysed
      through thematic analysis with final themes identified. RESULTS: Several core
      themes emerged from the narratives regardless of birth order. The most
      significant was the "need to protect." Additional themes were "things will never
      be the same," "unique bond," "shifting priorities" and "lost innocence."
      CONCLUSIONS AND RELEVANCE TO PRACTICE: The research shows activation of the
      Caregiving Behavioral Response System as it relates as a reciprocal to Attachment
      Theory.

PMID- 30184274
TI  - Determining the impact of a bowel management protocol on patients and clinicians'
      compliance in cardiac intensive care: A mixed-methods approach.
AB  - BACKGROUND: Bowel management protocols standardise care and, potentially, improve
      the incidence of diarrhoea and constipation in intensive care. However, little
      research exists reporting compliance with such protocols in intensive care
      throughout patients' stay. Furthermore, there is a limited exploration of the
      barriers and enablers to bowel management protocols following their
      implementation, an important aspect of improving compliance. AIM AND OBJECTIVE:
      To investigate the impact of a bowel management protocol on the incidence of
      constipation and diarrhoea, levels of compliance, and to explore the enablers and
      barriers associated with its use in intensive care. METHODS: A mixed-methods
      study was conducted in cardiac intensive care using two phases: (a) a
      retrospective case review of patients' hospital notes, before and after the
      protocol implementation, establishing the levels of diarrhoea and constipation
      and levels of compliance; (b) focus groups involving users of the protocol, 6
      months following its implementation, exploring the barriers and enablers in
      practice. RESULTS AND FINDINGS: Fifty-one patients' notes were reviewed during
      phase one: 30 pre-implementation and 21 post-implementation. Following the
      protocol implementation, there was a tendency for a higher incidence of
      constipation and less severe cases of diarrhoea. Overall compliance with the
      protocol was low (2.3%). However, there was evidence of behavioural change
      following protocol implementation, including less variation in aperients given
      and a shorter, less varied time period between starting enteral feed and
      administering aperients. Several themes emerged from the focus groups: barriers
      and enablers to the protocol characteristics and dissemination; barriers to bowel
      assessment; nurse as a barrier; medical involvement and protocol outcomes.
      CONCLUSIONS: The bowel management protocol implementation generated some positive
      outcomes to bowel care practices. However, compliance was low and until there is
      improvement, through overcoming the barriers identified, the impact of such
      protocols in practice will remain largely unknown.

PMID- 30184275
TI  - The Impact of Emotional Intelligence on Conflict Management Styles Used by
      Jordanian Nurse Managers.
AB  - BACKGROUND: Emotional intelligence was reported to help managers to effectively
      deal with conflicts in the workplace. However, the correlation between conflict
      management styles and emotional intelligence was still not fully conceptualized.
      AIM: To examine the impact of demographic variables and emotional intelligence on
      conflict management styles among nurse managers from Jordan. METHOD: A
      descriptive correlational design was used. A sample of 248 nurse managers
      completed the study. RESULTS: The integrating style was the most commonly used
      style among Jordanian nursing managers, while the least frequently used style was
      the dominating style. The conflict management styles significantly differed
      according to hospital type and years of experience. There were significant
      relationships between emotional intelligence and conflict management styles, but
      the direction of this relationship is not fully consistent with previous
      literature. CONCLUSION: Training nursing managers on emotional intelligence might
      improve their abilities to manage conflicts in the workplace. However, cultural
      factors might have a role in determining the conflict management style to be used
      by managers. IMPLICATIONS FOR NURSING MANAGEMENT: An analysis of the relationship
      between emotional intelligence and conflict management styles, will assist
      management in initiating a tailor-training program to improve the abilities to
      manage conflict management. This article is protected by copyright. All rights
      reserved.

PMID- 30184276
TI  - Fluconazole resistance is not a predictor of poor outcome in patients with
      cryptococcosis.
AB  - BACKGROUND: Cryptococcus isolates with high MICs to fluconazole are increasingly
      reported and a potential clinical impact has been advocated. However, there are
      different methods to evaluate fluconazole MICs and comparative analysis among
      such techniques and their comprehensive correlation with clinical outcome are not
      available. METHODS: Over a 13-year period (2000-2013), fluconazole MICs were
      determined for 62 cryptococcal isolates recovered from 22 patients with
      cryptococcosis using CLSI M27-A3, EUCAST, E-test and Sensititre YeastOne,
      simultaneously. The relationship between the fluconazole MICs, and the clinical
      outcome at week 10 was assessed in patients who received fluconazole as induction
      or maintenance therapy (n=16). RESULTS: The percentage of cryptococcal strains
      with MIC values >= 16 MUg/mL according to different methods was CLSI 1.6%, EUCAST
      16.1%, E-test 31.6%, and Sensititre YeastOne 56.2%. Among the 16 patients treated
      with fluconazole, no correlation between clinical outcome and any MIC value
      obtained with either method was observed. The only variable independently
      associated with a poor outcome was having a disseminated disease. CONCLUSIONS:
      There is a weak correlation between fluconazole MICs against Cryptococcus spp. as
      determined by CLSI, EUCAST, E-test and Sensititre YeastOne. Neither procedure
      could predict the clinical outcome of patients with cryptococcosis receiving
      fluconazole-based therapy. With present methods, fluconazole resistance in
      Cryptococcus may be clinically misleading. This article is protected by
      copyright. All rights reserved.

PMID- 30184278
TI  - Time to redefine post-exercise pressure decrease and post-exercise ankle-brachial
      index to diagnose peripheral artery disease.

PMID- 30184277
TI  - Cyberlindnera fabianii fungaemia outbreak in preterm neonates in Kuwait and
      literature review.
AB  - BACKGROUND: Cyberlindnera fabianii has rarely been reported as a human pathogen.
      Here, we describe an outbreak of C. fabianii fungaemia involving 10 preterm
      neonates during a seven-month period in Kuwait and review the published reports.
      METHODS: Blood cultures were processed, and yeast isolates were initially
      identified by ID 32 C and/or VITEK 2. Molecular identification was done by PCR
      sequencing of internally transcribed spacer (ITS) region and D1/D2 domains of
      rDNA. Fingerprinting was performed with microsatellite-based and minisatellite
      based primers to examine genetic relatedness among the isolates. Antifungal
      susceptibility testing of the isolates was done by Etest. FINDINGS: All infected
      neonates were preterm, received prior antibiotics and had an intravascular
      catheter in place. All bloodstream isolates were initially identified as Candida
      utilis by ID 32 C and/or VITEK 2 and showed reduced susceptibility to triazoles.
      PCR sequencing of rDNA identified all isolates as Cyberlindnera fabianii.
      Fingerprinting studies yielded identical patterns indicating clonality. One
      neonate died before treatment, one died during treatment, and eight neonates
      survived treatment with amphotericin B with/without fluconazole or caspofungin.
      Source of infection remained unknown despite surveillance cultures. CONCLUSION:
      The outbreak highlights emergence of C. fabianii as a neonatal pathogen and
      reinforces importance of molecular methods in its accurate identification.

PMID- 30184280
TI  - Monocytes accumulate in the airways of children with fatal asthma.
AB  - BACKGROUND: Activated T helper type 2 (Th2) cells are believed to play a pivotal
      role in allergic airway inflammation, but which cells attract and activate Th2
      cells locally have not been fully determined. Recently, it was shown in an
      experimental human model of allergic rhinitis (AR) that activated monocytes
      rapidly accumulate in the nasal mucosa after local allergen challenge, where they
      promote recruitment of Th2 cells and eosinophils. OBJECTIVE: To investigate
      whether monocytes are recruited to the lungs in paediatric asthma. METHODS:
      Tissue samples obtained from children and adolescents with fatal asthma attack (n
      = 12), age-matched non-atopic controls (n = 9) and allergen-challenged AR
      patients (n = 8) were subjected to in situ immunostaining. RESULTS: Monocytes,
      identified as CD68+S100A8/A9+ cells, were significantly increased in the lower
      airway mucosa and in the alveoli of fatal asthma patients compared with control
      individuals. Interestingly, cellular aggregates containing CD68+S100A8/A9+
      monocytes obstructing the lumen of bronchioles were found in asthmatics (8 out of
      12) but not in controls. Analysing tissue specimens from challenged AR patients,
      we confirmed that co-staining with CD68 and S100A8/A9 was a valid method to
      identify recently recruited monocytes. We also showed that the vast majority of
      accumulating monocytes both in the lungs and in the nasal mucosa expressed matrix
      metalloproteinase 10, suggesting that this protein may be involved in their
      migration within the tissue. CONCLUSIONS AND CLINICAL RELEVANCE: Monocytes
      accumulated in the lungs of children and adolescents with fatal asthma attack.
      This finding strongly suggests that monocytes are directly involved in the
      immunopathology of asthma and that these pro-inflammatory cells are potential
      targets for therapy.

PMID- 30184281
TI  - Endovascular therapy after acute ischaemic stroke-Experiences and needs of
      relatives.
AB  - AIMS AND OBJECTIVES: To explore the experiences and needs of relatives being part
      of the endovascular therapy (EVT) pathway. BACKGROUND: Ischaemic stroke is the
      third leading cause of death and the most common cause of acquired disability
      among adults in the Western world. The most recently approved treatment for major
      stroke is EVT. Removing the arterial occlusion has proven to be the best
      predictor of outcome. While patients are treated, relatives are left waiting.
      Facing the massive shock of their loved ones having a stroke may cause emotional
      turmoil and leave relatives with various needs. No previous studies have explored
      experiences and needs of relatives who are part of an EVT pathway. DESIGN: A
      qualitative design using a phenomenological-hermeneutic approach. METHODS: Semi
      structured interviews and participant observations were carried out. Data were
      collected from April 2016-January 2017. Data were analysed using Ricoeur's theory
      of interpretation, capturing meaning and ensuring comprehensive understanding.
      RESULTS: Four themes emerged are as follows: (a) The first phase-shock, chaos and
      feeling paralysed; (b) the all-important information-sharing is pivotal; (c)
      professional loving care-being seen and heard by caring health professionals; and
      (d) adjusting to new roles. One essential finding that emerged across all themes
      was relatives' constant need for care, for support and for health professionals
      to "be there." CONCLUSION: Relatives need support and care during the entire EVT
      pathway. They tend to be modest and ignore their own needs. Relatives who
      experience chaos, fear and worry need to be met by professionals with real
      presence. RELEVANCE TO CLINICAL PRACTICE: These findings will be used as a
      foundation for development of local structures and policies that should provide
      knowledge and ensure a consistent and proactive approach to meet the needs of the
      relatives in a timely and efficient manner.

PMID- 30184282
TI  - Social support network of family members of abused children and adolescents:
      Perspectives and possibilities.
AB  - AIMS AND OBJECTIVES: To analyse the network of care and social support from the
      perspectives of family members of children and adolescents who have been abused.
      BACKGROUND: The theoretical-methodological background of the ecological model for
      understanding violence and the Paradigm of Complexity provide a broad perspective
      of violence. The paradigm considers all aspects that constitute a phenomenon as
      well as particular features. DESIGN: Qualitative research based on the Paradigm
      of Complexity, developed by Edgar Morin, the primary philosopher. We have adhered
      to the COREQ Checklist guidelines for qualitative research. METHODS: Data were
      collected through Minimal Maps of Personal Social Networks, and semi-structured
      interviews were held with 15 families who were assisted by a nongovernmental
      organisation in a Brazilian city. The notions of comprehension and
      contextualisation guided the data analysis. RESULTS: Two categories emerged from
      the data analyses: "Social isolation" and "Affective relationships needs." The
      maps revealed a weakened and limited network with low-density, homogeneous bonds
      and few significant bonds. Therefore, the network provided predominantly
      instrumental and material social support with few important effective
      relationships. The participants disclosed some strategies to empower their lives.
      CONCLUSIONS: We conclude that it is urgent to develop strategies in a broad
      manner to promote family empowerment, especially on education and employment
      dimension, and to construct supportive and respectful relationships between
      services and families as well. RELEVANCE TO CLINICAL PRACTICE: The present study
      contributes to international clinical nursing, especially in low- and middle
      income countries, by discussing (a) looking at and caring for family members of
      children and adolescents who have been abused in a contextualised manner; (b)
      family empowerment, which enables them to have access to healthier environments
      and to educational/employment opportunities; and (c) broad comprehension of
      health care among the family members, which provides perspectives not only for
      looking at violence but also for strengthening supportive social relationships.

PMID- 30184283
TI  - Symptoms of apathy and passivity in dementia: A simultaneous concept analysis.
AB  - AIMS AND OBJECTIVES: The objective of this analysis was to clarify the concepts
      of apathy and passivity in the context of dementia by identifying distinguishing
      and overlapping attributes for both concepts simultaneously. BACKGROUND: Apathy
      is among the most common and persistent symptoms in dementia. The concept of
      apathy is often used interchangeably with passivity. Understanding similarities
      and differences between these concepts is of critical importance in clarifying
      clinical diagnostic criteria, developing consistent measurement in research and
      translating research evidence into nursing practice. DESIGN: A systematic
      literature search of multiple databases identified relevant articles for review.
      A modified combination of Haase et al.'s simultaneous concept analysis method and
      Morses' principle-based concept analysis using qualitative content and thematic
      analysis procedures was applied to identify overlapping and distinguishing
      attributes. METHODS: A search of PubMed, CINAHL and PsycINFO databases identified
      176 articles meeting inclusion criteria. The concepts of apathy and passivity
      were characterised using a standardised manual to identify attributes of
      definitions (conceptual and operational), related conditions, functional,
      behavioural and neurobiological correlates, antecedents and consequences.
      Thematic analysis identified common themes across each category which were
      tabulated and entered into comparative matrices to identify overlapping and
      distinguishing features. RESULTS: There is considerable overlap across attributes
      of apathy and passivity. Apathy is distinguished as a clinical syndrome
      characterised by loss of motivation not due to emotional distress or cognitive
      impairment. Passivity is distinguished as a lack of interaction between the
      individual and environment in the context of cognitive impairment. CONCLUSION: In
      contrast to passivity, apathy is a more robustly defined concept focused on
      motivational limitations within the individual associated with specific
      neuroanatomical deficits. RELEVANCE TO CLINICAL PRACTICE: The identification of
      key distinguishing features of apathy and passivity in dementia is a critical
      first step in ensuring consistent measurement of each concept.

PMID- 30184284
TI  - Identification of a conserved DNA sulfur recognition domain by characterizing the
      phosphorothioate-specific endonuclease SprMcrA from Streptomyces
      pristinaespiralis.
AB  - Streptomyces species have been valuable models for understanding the phenomenon
      of DNA phosphorothioation in which sulfur replaces a non-bridging oxygen in the
      phosphate backbone of DNA. We previously reported that the restriction
      endonuclease ScoMcrA from Streptomyces coelicolor cleaves phosphorothioate DNA
      and Dcm-methylated DNA at sites 16-28 nucleotides away from the modification
      sites. However, cleavage of modified DNA by ScoMcrA is always incomplete and
      accompanied by severe promiscuous activity on unmodified DNA. These features
      complicate the studies of recognition and cleavage of phosphorothioate DNA. For
      these reasons, we here characterized SprMcrA from Streptomyces pristinaespiralis,
      a much smaller homolog of ScoMcrA with a rare HRH motif, a variant of the HNH
      motif that forms the catalytic center of these endonucleases. The sulfur-binding
      domain of SprMcrA and its phosphorothioation recognition site were determined.
      Compared to ScoMcrA, SprMcrA has higher specificity in discerning
      phosphorothioate DNA from unmodified DNA, and this enzyme generally cuts both
      strands at a distance of 11-14 nucleotides from the 5' side of the recognition
      site. The HRH/HNH motif has its own sequence specificity in DNA hydrolysis,
      leading to failure of cleavage at some phosphorothioated sites. An R248N mutation
      of the central residue in HRH resulted in 30-fold enhancement in cleavage
      activity of phosphorothioate DNA and altered the cleavage efficiency at some
      sites, whereas mutation of both His residues abolished restriction activity. This
      is the first report of a recognition domain for phosphorothioate DNA and
      phosphorothioate-dependent and sequence-specific restriction activity.

PMID- 30184285
TI  - The role of medical mycology societies in combating invasive fungal infections in
      low- and middle-income countries: A Nigerian model.
AB  - The discipline of medical mycology has become increasingly relevant in the face
      of the rising incidence of invasive fungal infections (IFI), which pose
      diagnostic and therapeutic challenges for contemporary medical practice. While
      firmly established in developed countries, medical mycology remains obscure in
      many low- and middle-income countries (LMICs). With a teeming vulnerable populace
      and an incidence rate of 11.8%, Nigeria has one of the highest estimated burdens
      of invasive fungal infections (IFIs) in the world. Regardless, the scourge of
      IFIs has remained silent due to a combination of factors principal amongst which
      are a lack of awareness and dearth in personnel skilled in diagnosis. The present
      narrative examines the status of medical mycology practice in Nigeria and
      chronicles the journey to change the status quo spurred by the Leading
      International Fungal Education (LIFE)-facilitated burden estimate paper and
      culminating in the birth of the Medical Mycology Society of Nigeria (MMSN), the
      pioneer national medical mycology society in Africa. The prospects of tackling
      the IFI challenge are highlighted from the perspective of the nascent society.

PMID- 30184286
TI  - Fast and pH-Independent Elimination of trans-Cyclooctene by Using Aminoethyl
      Functionalized Tetrazines.
AB  - The inverse-electron-demand Diels-Alder/pyridazine elimination tandem reaction,
      in which the allylic substituent on trans-cyclooctene is eliminated following
      reaction with tetrazines, is gaining interest as a versatile bioorthogonal
      process. One potential shortcoming of such currently used reactions is their
      propensity to proceed faster and more efficiently at lower pH, a feature caused
      by the nature of the tetrazines used. Here, we present aminoethyl-substituted
      tetrazines as the first pH-independent reagents showing invariably fast
      elimination kinetics at all biologically relevant pH values.

PMID- 30184287
TI  - Physiological adaptations to resistance training in rats selectively bred for low
      and high response to aerobic exercise training.
AB  - NEW FINDINGS: What is the central question of this study? Can phenotypic traits
      associated with low response to one mode of training be extrapolated to other
      exercise-inducible phenotypes? The present study investigated whether rats that
      are low responders to endurance training are also low responders to resistance
      training. What is the main finding and its importance? After resistance training,
      rats that are high responders to aerobic exercise training improved more in
      maximal strength compared with low-responder rats. However, the greater gain in
      strength in high-responder rats was not accompanied by muscle hypertrophy,
      suggesting that the responses observed could be mainly neural in origin.
      ABSTRACT: The purpose of this study was to determine whether rats selectively
      bred for low and high response to aerobic exercise training co-segregate for
      differences in muscle adaptations to ladder-climbing resistance training. Five
      high-responder (HRT) and five low-responder (LRT) rats completed the resistance
      training, while six HRT and six LRT rats served as sedentary control animals.
      Before and after the 6 week intervention, body composition was determined by dual
      energy X-ray absorptiometry. Before tissue harvesting, the right triceps surae
      muscles were loaded by electrical stimulation. Muscle fibre cross-sectional
      areas, nuclei per cell, phosphorylation status of selected signalling proteins of
      mTOR and Smad pathways, and muscle protein, DNA and RNA concentrations were
      determined for the right gastrocnemius muscle. The daily protein synthesis rate
      was determined by the deuterium oxide method from the left quadriceps femoris
      muscle. Tissue weights of fore- and hindlimb muscles were measured. In response
      to resistance training, maximal carrying capacity was greater in HRT (~3.3 times
      body mass) than LRT (~2.5 times body mass), indicating greater improvements of
      strength in HRT. However, muscle hypertrophy that could be related to greater
      strength gains in HRT was not observed. Furthermore, noteworthy changes within
      the experimental groups or differences between groups were not observed in the
      present measures. The lack of hypertrophic muscular adaptations despite
      considerable increases in muscular strength suggest that adaptations to the
      present ladder-climbing training in HRT and LRT rats were largely induced by
      neural adaptations.

PMID- 30184288
TI  - Regiocontrolled Remote C-H Olefination of Small Heterocycles.
AB  - Achieving site-selective C-H functionalization of arene is a fundamental
      challenge, as it is mainly controlled by the electronic nature of the molecules.
      A chelation-assisted C-H functionalization strategy overcomes the selectivity
      issues by utilizing distance and geometry of covalently attached directing groups
      (DGs). This strategy requires stoichiometric DG installation/removal and a
      suitable functional group on which to tether the DG. Such strategies are
      ineffective for small heterocycles unless suitable functional groups are added.
      Moreover, heterocycles are not the judicious choice as substrates owing to the
      possibilities of catalyst deactivation. Inspired by recent developments, this
      work demonstrates the utilization of a chelating template backbone bearing
      covalently attached directing groups, which enables site-selective remote C-H
      functionalization of heterocycles. The observed selectivity is the outcome of non
      covalent interactions between the heterocycles and bifunctional template
      backbone.

PMID- 30184289
TI  - Ethical issues in the care of patients with stroke: A scoping review.
AB  - AIMS AND OBJECTIVES: The aim was to identify and analyse the ethical issues in
      the care of patients with stroke (PwS). The goal was to understand the nature of
      the existing knowledge on the topic and to identify whether there are ethical
      issues specific to the care of PwS. BACKGROUND: Stroke is a disease with possible
      multiple effects on the patient's overall condition and experienced ethical
      issues in the care. Additionally, stroke impacts the life of the significant
      other. For health professionals, the care of PwS is challenging at different
      stages of the care process. The care of stroke includes several ethically
      sensitive situations from the perspectives of all participants. DESIGN: Scoping
      review. METHODS: The review was conducted following the five-stage methodological
      framework of Arksey and O'Malley (2005). The literature search was conducted in
      several electronic databases and complemented with a manual search, resulting in
      15 reviewed articles. The analysis was conducted by charting descriptive
      numerical data and by content analysis of the narrative representations. RESULTS:
      The studies focused on hospital or rehabilitation contexts and a high number of
      studies had a qualitative approach. Three main themes were identifiable:
      "decision-making as an ethically challenging act," "care process-specific ethical
      issues" and "environmental ethical issues." CONCLUSIONS: Ethical issues occur at
      different stages of the care process of PwS and from the viewpoints of all those
      involved. However, not all the recognised ethical issues were stroke specific. As
      the number of the reviewed articles was limited, more research is needed for a
      comprehensive understanding of the topic. RELEVANCE TO CLINICAL PRACTICE:
      Individual health professionals may use the results in observing their own action
      from an ethical perspective and to deepen the ethical understanding of the care
      of PwS. In health care organisations, the results may be used in developing the
      ethical quality of care.

PMID- 30184291
TI  - Vaccine-preventable disease following allogeneic haematopoietic stem cell
      transplant in Western Australia.
AB  - AIM: Infection is an important and frequent cause of mortality and morbidity
      following allogeneic haematopoietic stem cell transplantation (HSCT). This study
      was conducted to determine the epidemiology and clinical phenotype of vaccine
      preventable disease in children who have undergone HSCT following the
      implementation of a standard revaccination programme. METHODS: Children receiving
      first allogeneic HSCT in Western Australia between January 2005 and December 2014
      were eligible for recruitment. Patients received standard antimicrobial
      prophylaxis and were vaccinated according to the West Australian post-HSCT
      immunisation schedule, commencing 6 months following HSCT. Children who developed
      any illness post-HSCT were reviewed, and investigations for infectious disease
      were undertaken as clinically indicated. Positive identification of vaccine
      preventable disease was documented with the clinical course of the illness.
      RESULTS: A total of 71 patients were enrolled in the study. The overall incidence
      of vaccine-preventable disease following HSCT was 19.7%; influenza accounted for
      50% of all cases, herpes zoster for 42.9%. All episodes occurred late, beyond day
      100 post-HSCT. Overall survival for matched-sibling donor transplants was 83.3
      and 75.0% at 1 and 5 years, respectively, and was 72.3 and 63.3% for alternative
      donor transplants. Mortality due to vaccine-preventable disease was low, with one
      death from disseminated herpes zoster. CONCLUSIONS: There is a high incidence of
      vaccine-preventable morbidity post-allogeneic HSCT in West Australian children.
      Viral aetiology constitutes the main burden, namely, influenza infection and
      varicella zoster virus reactivation. Further efforts are required to identify the
      most appropriate preventative strategies.

PMID- 30184290
TI  - The intellectual disability-associated CAMK2G p.Arg292Pro mutation acts as a
      pathogenic gain-of-function.
AB  - The abundantly expressed calcium/calmodulin-dependent protein kinase II (CAMK2),
      alpha (CAMK2A), and beta (CAMK2B) isoforms are essential for learning and memory
      formation. Recently, a de novo candidate mutation (p.Arg292Pro) in the gamma
      isoform of CAMK2 (CAMK2G) was identified in a patient with severe intellectual
      disability (ID), but the mechanism(s) by which this mutation causes ID is
      unknown. Here, we identified a second, unrelated individual, with a de novo
      CAMK2G p.Arg292Pro mutation, and used in vivo and in vitro assays to assess the
      impact of this mutation on CAMK2G and neuronal function. We found that knockdown
      of CAMK2G results in inappropriate precocious neuronal maturation. We further
      found that the CAMK2G p.Arg292Pro mutation acts as a highly pathogenic gain-of
      function mutation, leading to increased phosphotransferase activity and impaired
      neuronal maturation as well as impaired targeting of the nuclear CAMK2G isoform.
      Silencing the catalytic site of the CAMK2G p.Arg292Pro protein reversed the
      pathogenic effect of the p.Arg292Pro mutation on neuronal maturation, without
      rescuing its nuclear targeting. Taken together, our results reveal an
      indispensable function of CAMK2G in neurodevelopment and indicate that the CAMK2G
      p.Arg292Pro protein acts as a pathogenic gain-of-function mutation, through
      constitutive activity toward cytosolic targets, rather than impaired targeting to
      the nucleus.

PMID- 30184292
TI  - Limited phenological and dietary overlap between bee communities in spring
      flowering crops and herbaceous enhancements.
AB  - Wild bee populations have undergone declines in recent years across much of the
      Western world, and these declines have the potential to limit yield in
      pollination-dependent crops. Highbush blueberry, Vaccinium corymbosum, and tart
      cherry, Prunus cerasus, are spring-blooming crops that rely on the movement of
      pollen by bees and other insects for pollination. Wild bee populations can be
      increased on farmland by providing floral resources, but whether the addition of
      these plants translates into increased pollinator density on crop flowers has not
      been documented in most cropping systems. To determine the importance of
      providing additional floral resources for wild bee pollinator communities, we
      selected blueberry fields and tart cherry orchards with and without herbaceous
      floral enhancements in western Michigan, USA. The bee communities visiting crop
      flowers, enhancements and control grassy field margins were sampled over a 5-yr
      period. In addition, the pollen diets of the most abundant wild bee crop
      pollinators were quantified across Michigan to better understand their foraging
      niches and to identify potentially important alternative host plants. The
      presence of floral enhancements did not increase the abundance of wild bees on
      either blueberry or cherry flowers during bloom. The bee community visiting
      blueberry was evenly composed of short-season bees that fly only during the
      spring and long-season bees that fly in both spring and summer. In contrast, the
      bee community visiting cherry was dominated by short-season spring bees. The
      majority of pollen collected by the wild bee communities visiting blueberry and
      cherry was from spring-flowering woody plants, with limited use of the herbaceous
      enhancements. Enhancements attracted greater abundance and species richness of
      bees compared to control areas, including twice as many floral specialists.
      Conserving summer-flying, grassland-associated bees is an appropriate goal for
      pollinator conservation programs. However, herbaceous enhancements may not
      provide adequate resources for the wild bees that pollinate spring-flowering
      crops. This study demonstrates that an examination of the pollen collected by
      wild bees across their flight periods can identify plant species to help them
      persist in intensively managed landscapes.

PMID- 30184293
TI  - Rate of left ventricular pressure change by Doppler echocardiography in dogs with
      chronic mitral valve disease at different stages of congestive heart failure.
AB  - Although the major pathological feature of chronic mitral valve disease is mitral
      regurgitation, myocardial dysfunction has been suggested to be present in dogs
      with chronic mitral valve disease. However, accurate assessment of myocardial
      function remains challenging. Doppler-derived rate of left ventricular pressure
      change is a simple, less load-dependent method for evaluating myocardial
      function. We aimed to evaluate Doppler-derived rate of left ventricular pressure
      change for assessing myocardial function in different stages of dogs with chronic
      mitral valve disease. This analytical cross-sectional study recruited 55 client
      owned dogs with chronic mitral valve disease prospectively. Based on physical
      examination, indirectly measured blood pressure, routine hematologic and
      biochemistry examinations, thoracic radiography, electrocardiography, and
      echocardiography, dogs were diagnosed as mitral valve disease and excluded for
      systemic diseases and other cardiac diseases. They were classified according to
      the International Small Animal Cardiac Health Council scales. Doppler-derived
      rates of left ventricular pressure rise and fall (dP/dt and -dP/dt) were analyzed
      by two investigators using continuous-wave Doppler imaging. Doppler-derived dP/dt
      was higher in dogs of class IIIa than in those of the other classes, whereas
      values of -dP/dt decreased significantly with the severity of congestive heart
      failure. The peak velocity of the early diastolic wave and -dP/dt were identified
      as independent predictors of congestive heart failure. Our findings suggested
      that Doppler-derived dP/dt and -dP/dt, used in combination with conventional
      echocardiographic variables, could allow a better understanding of myocardial
      dysfunction and a possibility for prediction of the risk of heart failure in dogs
      with chronic mitral valve disease.

PMID- 30184294
TI  - Resection of recto-vaginal deep infiltrating endometriosis nodules: an innovative
      laparoscopic technique - a video vignette.

PMID- 30184295
TI  - Brainstem enlargement in preschool children with autism: Results from an
      intermethod agreement study of segmentation algorithms.
AB  - The intermethod agreement between automated algorithms for brainstem segmentation
      is investigated, focusing on the potential involvement of this structure in
      Autism Spectrum Disorders (ASD). Inconsistencies highlighted in previous studies
      on brainstem in the population with ASD may in part be a result of poor agreement
      in the extraction of structural features between different methods. A sample of
      76 children with ASD and 76 age-, gender-, and intelligence-matched controls was
      considered. Volumetric analyses were performed using common tools for brain
      structures segmentation, namely FSL-FIRST, FreeSurfer (FS), and Advanced
      Normalization Tools (ANTs). For shape analysis SPHARM-MAT was employed.
      Intermethod agreement was quantified in terms of Pearson correlations between
      pairs of volumes obtained by the different methods. The degree of overlap between
      segmented masks was quantified in terms of the Dice index. Both Pearson
      correlations and Dice indices, showed poor agreement between FSL-FIRST and the
      other methods (ANTs and FS), which by contrast, yielded Pearson correlations
      greater than 0.93 and average Dice indices greater than 0.76 when compared with
      each other. As with volume, shape analyses exhibited discrepancies between
      segmentation methods, with particular differences noted between FSL-FIRST and the
      others (ANT and FS), with under- and over-segmentation in specific brainstem
      regions. These data suggest that research on brain structure alterations should
      cross-validate findings across multiple methods. We consistently detected an
      enlargement of brainstem volume in the whole sample and in the male cohort across
      multiple segmentation methods, a feature particularly driven by the subgroup of
      children with idiopathic intellectual disability associated with ASD.

PMID- 30184296
TI  - Design of Artificial Alcohol Oxidases: Alcohol Dehydrogenase-NADPH Oxidase
      Fusions for Continuous Oxidations.
AB  - To expand the arsenal of industrially applicable oxidative enzymes, fusions of
      alcohol dehydrogenases with an NADPH-oxidase were designed. Three different
      alcohol dehydrogenases (LbADH, TbADH, ADHA) were expressed with a thermostable
      NADPH-oxidase fusion partner (PAMO C65D) and purified. The resulting bifunctional
      biocatalysts retained the catalytic properties of the individual enzymes, and
      acted essentially like alcohol oxidases: transforming alcohols to ketones by
      using dioxygen as mild oxidant, while merely requiring a catalytic amount of
      NADP+ . In small-scale reactions, the purified fusion enzymes show good
      performances, with 69-99 % conversion, 99 % ee with a racemic substrate, and high
      cofactor and enzyme total turnover numbers. As the fusion enzymes essentially act
      as oxidases, we found that commonly used high-throughput oxidase-activity
      screening methods can be used. Therefore, if needed, the fusion enzymes could be
      easily engineered to tune their properties.

PMID- 30184297
TI  - Transanal anastomotic techniques for rectal cancer: the reverse air leak test - a
      video vignette.

PMID- 30184298
TI  - Stapled transanal rectal resection for rectocele after endoscopic mucosal
      resection - a video vignette.

PMID- 30184300
TI  - Implementing safety hotlines: Stamford Health's experience and future
      opportunities.
AB  - Improving safety event reporting has been a focus of increased study. Improved
      opportunities for patient and family safety event reporting have been described
      in the literature. Consistent with the organization's patient-centered care
      philosophy, we launched a safety hotline at Stamford Health. This article
      describes the process of implementation, vendor selection, understanding initial
      results, and areas for further study.

PMID- 30184299
TI  - Progesterone and plasma metabolites in women with and in those without
      premenstrual dysphoric disorder.
AB  - BACKGROUND: The molecular mechanisms underpinning the progesterone-triggering
      mood symptoms in women with premenstrual dysphoric disorder (PMDD) are unknown.
      Cell metabolism is a potential source of variability. Very little is known about
      the effect of progesterone sensitivity on the metabolome. In this study, we aimed
      to characterize the effects of progesterone on the global metabolic profile and
      explore the differences between women with PMDD and controls. METHODS: Plasma was
      obtained from 12 women with prospectively confirmed PMDD and 25 controls under
      two hormone conditions: (1) gonadal suppression induced by leuprolide acetate
      (3.75 mg IM monthly) and (2) add-back phase with leuprolide and progesterone (200
      mg twice daily by vaginal suppository). The global metabolic profile was obtained
      using liquid and gas chromatography followed by mass spectrometry. Differences
      between groups and time points were tested using repeated measures analysis of
      variance. The false discovery rate was calculated to account for multiple
      testing. RESULTS: Amino acids and their derivatives represented 78% (28/36) of
      the known compounds that were found in significantly lower plasma concentrations
      after progesterone administration than during gonadal suppression. The
      concentration of tyrosine was nominally significantly decreased after
      progesterone add-back in controls, but not in cases (P = 0.02). CONCLUSION:
      Plasma levels of some amino acids are decreased in response to progesterone.
      Albeit preliminary, evidence further suggests that progesterone has a different
      effect on the metabolic profiles of women with PMDD compared to controls. Further
      research is needed to replicate our findings in a larger sample and to identify
      the unknown compounds, especially those differentially expressed.

PMID- 30184301
TI  - Activation of brainstem and midbrain nuclei during cognitive control in medicated
      patients with schizophrenia.
AB  - Evidence suggests that cognitive control functions as well as the underlying
      brain network, anchored by the prefrontal cortex (PFC) and the dorsal anterior
      cingulate cortex (dACC), are dysfunctional in schizophrenia. Catecholamine
      producing midbrain and brainstem nuclei are densely connected with the PFC and
      dACC and exert profound contributions to cognitive control processes.
      Dysfunctions within the underlying neurotransmitter systems are considered to
      play a central role in the occurrence of various symptoms of schizophrenia. We
      sought to investigate the putatively abnormal activation pattern of the
      dopaminergic midbrain nuclei, that is, ventral tegmental area (VTA) and
      substantia nigra as well as that of the noradrenergic locus coeruleus (LC) in
      patients with schizophrenia during cognitive control. A total of 28 medicated
      patients and 27 healthy controls were investigated with the manual version of the
      Stroop task using event-related fMRI. The main finding was a reduced BOLD
      activation in the VTA during both Stroop task conditions in patients in
      comparison to controls, which correlated significantly with the degree of
      negative symptoms. We further detected a comparable LC activation in in patients
      and healthy controls. However, in controls LC activation was significantly
      correlated with the Stroop interference time, which was not observed in patients.
      The finding of reduced VTA activation in schizophrenia patients lends further
      support to the assumed dysfunction of the DA system in schizophrenia. In
      addition, despite comparable LC activation, the nonsignificant correlation with
      the Stroop interference time might indicate altered LC functioning in
      schizophrenia and, thus, needs further investigations.

PMID- 30184302
TI  - A pharmacist-driven antimicrobial stewardship intervention targeting
      cytomegalovirus viremia in ambulatory solid organ transplant recipients.
AB  - BACKGROUND: There is a growing need for robust antimicrobial stewardship
      interventions in both ambulatory and solid organ transplant (SOT) populations.
      METHODS: A retrospective quasi-experiment was conducted to evaluate the impact of
      a pharmacist-driven antimicrobial stewardship intervention targeting
      cytomegalovirus (CMV) viremia in ambulatory SOT recipients. The intervention
      consisted of (a) real-time CMV DNA surveillance and result notification conducted
      by the pharmacist and (b) recommendations for the optimization of drug therapy
      provided at the time of result notification. The intervention period was compared
      to a pre-intervention period of usual care. Of 431 adult SOT recipients who had
      an initial quantifiable CMV viral load in the ambulatory setting, 185 received
      antiviral induction therapy and were included for analysis. RESULTS:
      Significantly fewer patients in the intervention period reached a CMV viral load
      >10 000 IU/mL immediately prior to treatment (10.6% vs 27.3%; P = 0.004), and a
      significantly greater proportion of patients in the intervention period achieved
      CMV eradication at 21 days (84.5% vs 71.7%; P = 0.038). Additional differences
      favoring the intervention period were antiviral initiation within 5 days of the
      first quantifiable CMV DNA (62.4% vs 55.0%; P = 0.02) and time-to-CMV eradication
      (25.5 vs 28.9 days; P = 0.003). Although not significant, there were also
      numerical reductions in CMV-related hospital admissions (11.9% vs 19.0%; P =
      0.188) and CMV disease (5.9% vs 12.0%; P = 0.151) during the intervention period,
      as well as fewer episodes of CMV resistance at 1-year (2.3% vs 4.0%; P = 0.689).
      CONCLUSION: Together, these findings suggest a potential role for pharmacist
      involvement in CMV surveillance and treatment optimization in ambulatory SOT
      recipients.

PMID- 30184303
TI  - One for all and all for one: retention of colour-unchanged old flowers increases
      pollinator attraction in a hermaphroditic plant.
AB  - Long-lived flowers increase pollen transfer rates, but these entail high water
      and carbon maintenance costs. The retention of pollinated and reward-free old
      flowers enhances pollinator visitation to young receptive flowers by increasing
      floral display size. This mechanism is associated with acropetal inflorescences
      or changes in flower colour and openness, but the retention of unchanging
      solitary flowers remains overlooked. We examined pollination-dependent variation
      in floral longevity and determined stigmatic receptivity, pollen viability and
      pollen removal rates among flower ages in Kielmeyera regalis, a Neotropical
      savanna shrub. We also evaluated the effects of floral display size on pollinator
      visitation rates. Lastly, we determined whether old flowers are unvisited and
      exclusively increase pollinator attraction to young flowers through flower
      removal experiments. Regardless of pollination treatment, flowers lasted fully
      open with no detectable physical changes for 3 days. Over time, stigmas remained
      receptive but >95% of pollen was removed. Pollinator visitation significantly
      increased with floral display size and intermediate percentages (15-30%) of newly
      opened flowers. Accordingly, the retention of reward-free and unvisited old
      flowers increased young flower-pollinator interaction. Our results reveal the
      importance of a prolonged floral longevity in increasing pollinator attraction
      toward newly opened receptive flowers without changes in flower colour and form.
      We conclude that the retention of pollinated, reward-free and unvisited colour
      unchanged old flowers in K. regalis is a strategy that counteracts the water use
      costs associated with the maintenance of large flowers with increased mate
      opportunities in a pollen-limited scenario.

PMID- 30184304
TI  - Local and Global Dynamics in Intrinsically Disordered Synuclein.
AB  - Intrinsically disordered proteins (IDPs) experience a diverse spectrum of motions
      that are difficult to characterize with a single experimental technique. Herein
      we combine high- and low-field nuclear spin relaxation, nanosecond fluorescence
      correlation spectroscopy (nsFCS), and long molecular dynamics simulations of
      alpha-synuclein, an IDP involved in Parkinson disease, to obtain a comprehensive
      picture of its conformational dynamics. The combined analysis shows that fast
      motions below 2 ns caused by local dihedral angle fluctuations and conformational
      sampling within and between Ramachandran substates decorrelate most of the
      backbone N-H orientational memory. However, slow motions with correlation times
      of up to ca. 13 ns from segmental dynamics are present throughout the alpha
      synuclein chain, in particular in its C-terminal domain, and global chain
      reconfiguration occurs on a timescale of ca. 60 ns. Our study demonstrates a
      powerful strategy to determine residue-specific protein dynamics in IDPs at
      different time and length scales.

PMID- 30184305
TI  - Species-specific differences in water uptake depth of mature temperate trees vary
      with water availability in the soil.
AB  - Temperate tree species differ in their physiological sensitivity to declining
      soil moisture and drought. Although species-specific responses to drought have
      often been suggested to be the result of different water uptake depths, empirical
      evidence for such a mechanism is scarce. Here we test if differences in water
      uptake depths can explain previously observed species-specific physiological
      responses of temperate trees to drought and if the water uptake depth of
      different species varies in response to declining soil moisture. For this
      purpose, we employed stable oxygen and hydrogen isotopes of soil and xylem water
      that we collected over the course of three growing seasons in a mature temperate
      forest in Switzerland. Our data show that all investigated species utilise water
      from shallow soil layers during times of sufficient soil water supply. However,
      Fraxinus excelsior, Fagus sylvatica and Acer pseudoplatanus were able to shift
      their water uptake to deeper soil layers when soil water availability decreased
      in the topsoil. In contrast, Picea abies, was not able to shift its water uptake
      to deeper soil layers. We conclude from our data that more drought-resistant tree
      species are able to shift their water uptake to deeper soil layers when water
      availability in the topsoil is becoming scarce. In addition, we were able to show
      that water uptake depth of temperate tree species is a trait with high plasticity
      that needs to be characterised across a range of environmental conditions.

PMID- 30184306
TI  - Regularized aggregation of statistical parametric maps.
AB  - Combining statistical parametric maps (SPM) from individual subjects is the goal
      in some types of group-level analyses of functional magnetic resonance imaging
      data. Brain maps are usually combined using a simple average across subjects,
      making them susceptible to subjects with outlying values. Furthermore, t tests
      are prone to false positives and false negatives when outlying values are
      observed. We propose a regularized unsupervised aggregation method for SPMs to
      find an optimal weight for aggregation, which aids in detecting and mitigating
      the effect of outlying subjects. We also present a bootstrap-based weighted t
      test using the optimal weights to construct an activation map robust to outlying
      subjects. We validate the performance of the proposed aggregation method and test
      using simulated and real data examples. Results show that the regularized
      aggregation approach can effectively detect outlying subjects, lower their
      weights, and produce robust SPMs.

PMID- 30184307
TI  - Successful treatment of giant condyloma in a pediatric heart transplant recipient
      with topical cidofovir.
AB  - We report a case of giant condyloma that developed in a pediatric heart
      transplant recipient. This infection progressed for several months despite
      reduction in immunosuppression, topical treatment, and oral cimetidine therapy.
      Complete resolution was observed following 7 months of topical cidofovir, without
      evidence of systemic toxicity or rejection.

PMID- 30184308
TI  - Structure to Function in Supramolecular Polymers and Materials.

PMID- 30184309
TI  - Withstanding the test of time: Multisensory cues improve the delayed retention of
      incidental learning.
AB  - Multisensory tools are commonly employed within educational settings (e.g. Carter
      & Stephenson, ), and there is a growing body of literature advocating the
      benefits of presenting children with multisensory information over unisensory
      cues for learning (Baker & Jordan, ; Jordan & Baker, ). This is even the case
      when the informative cues are only arbitrarily related (Broadbent, White,
      Mareschal, & Kirkham, ). However, the delayed retention of learning following
      exposure to multisensory compared to unisensory cues has not been evaluated, and
      has important implications for the utility of multisensory educational tools.
      This study examined the retention of incidental categorical learning in 5-, 7-
      and 9-year-olds (N = 181) using either unisensory or multisensory cues. Results
      found significantly greater retention of learning following multisensory cue
      exposure than with unisensory information when category knowledge was tested
      following a 24-hour period of delay. No age-related changes were found,
      suggesting that multisensory information can facilitate the retention of learning
      across this age range.

PMID- 30184310
TI  - Impact of antiretroviral regimen on renal transplant outcomes in HIV-infected
      recipients.
AB  - BACKGROUND: Protease inhibitors (PI) pose a challenge post-transplant due to
      significant drug interactions with calcineurin inhibitors, prompting many
      clinicians to convert patients to non-interacting regimens prior to transplant.
      The purpose of this study was to examine the impact of PI-based regimens on graft
      outcomes in HIV-infected renal transplant recipients. METHODS: In this
      retrospective cohort study, 50 HIV-infected renal allograft recipients (27
      receiving a PI regimen, 23 receiving a non-PI regimen) transplanted between 2003
      2015 were analyzed. RESULTS: Cumulative rejection rates at 12 and 36 months were
      41% and 54% in the PI group vs 52% and 86% in the non-PI group. At last follow
      up, the overall risk of acute rejection in the PI group was 46% lower compared
      with the non-PI cohort (P = 0.12). Patients who received a PI-based regimen had
      significantly reduced graft failure rates (P = 0.027). There was no difference
      between groups in the degree of interstitial fibrosis/tubular atrophy, arteriolar
      hyalinosis, arterial sclerosis, or glomerular sclerosis on available biopsies,
      despite longer follow-up time in the PI group. CONCLUSIONS: Our study suggests
      that PI-based antiretroviral therapy regimens are associated with improved graft
      survival and that patients can achieve adequate outcomes on a PI-based regimen
      when necessary. Due to study limitations, further studies are needed to determine
      the optimal immunosuppression/antiretroviral therapy regimen post-transplant.

PMID- 30184311
TI  - Non-infectious diffuse vesiculobullous rash in a pancreas and renal transplant
      recipient.
AB  - Solid organ transplant patients are well established to be at risk of herpes
      simplex virus and varicella zoster virus infection and reactivation. We present a
      case of a 41-year-old woman with a history of pancreas and renal transplant who
      presented with what appeared to be disseminated herpes simplex virus or varicella
      zoster virus induced rash, but who was ultimately diagnosed and treated as linear
      IgA bullous dermatosis. This case alerts physicians to other non-infectious
      dermatoses as a cause of vesiculobullous rash in solid organ transplant patients.

PMID- 30184312
TI  - Insight into epileptic and physiological deja vu: from a multicentric cohort
      study.
AB  - BACKGROUND AND PURPOSE: The presence of a continuum between physiological deja vu
      (DV) and epileptic DV is still not known as well as epidemiological data in the
      Italian population. The aim was to identify the epidemiological distribution of
      DV in Italy, and secondly to look for specific features of DV able to
      discriminate between epileptic and non-epileptic DV. METHODS: In all, 1000
      individuals, 543 healthy controls (C) (313 women; age 40 +/- 15 years) and 457
      patients with epilepsy (E) (260 women; age 39 +/- 14 years), were prospectively
      recruited from 10 outpatient neurological clinics throughout Italy. All
      populations were screened using the Italian Inventory for Deja Vu Experiences
      Assessment (I-IDEA) test and E and pairwise C underwent a comprehensive epilepsy
      interview. RESULTS: Of E, 69% stated that they experienced 'recognition' and
      13.2% reported that this feeling occurred from a few times a month to at least
      weekly (versus 7.7% of the control group). Furthermore, a greater percentage of E
      (6.8% vs. 2.2%) reported that from a few times a month to at least weekly they
      felt that it seemed as though everything around was not real. In E, the feeling
      of recognition raised fright (22.3% vs. 13.2%) and a sense of oppression (19.4%
      vs. 9.4%). A fifth of E felt recognition during epileptic seizures. CONCLUSION:
      Only E regardless of aetiology firmly answered that they had the feeling of
      recognition during an epileptic seizure; thus question 14 of the I-IDEA test part
      2 discriminated E from C. Paranormal activity, remembering dreams and travel
      frequency were mostly correlated to DV in E suggesting that the visual-memory
      network might be involved in epileptic DV.

PMID- 30184313
TI  - Fourteen-month-old infants track the language comprehension of communicative
      partners.
AB  - Infants employ sophisticated mechanisms to acquire their first language,
      including some that rely on taking the perspective of adults as speakers or
      listeners. When do infants first show awareness of what other people understand?
      We tested 14-month-old infants in two experiments measuring event-related
      potentials. In Experiment 1, we established that infants produce the N400 effect,
      a brain signature of semantic violations, in a live object naming paradigm in the
      presence of an adult observer. In Experiment 2, we induced false beliefs about
      the labeled objects in the adult observer to test whether infants keep track of
      the other person's comprehension. The results revealed that infants reacted to
      the semantic incongruity heard by the other as if they encountered it themselves:
      they exhibited an N400-like response, even though labels were congruous from
      their perspective. This finding demonstrates that infants track the linguistic
      understanding of social partners.

PMID- 30184314
TI  - Synthesis of N-Heterocycles by Dehydrogenative Annulation of N-Allyl Amides with
      1,3-Dicarbonyl Compounds.
AB  - Dehydrogenative annulation under oxidizing reagent-free conditions is an ideal
      strategy to construct cyclic structures. Reported herein is an unprecedented
      synthesis of pyrrolidine and tetrahydropyridine derivatives through
      electrochemical dehydrogenative annulation of N-allyl amides with 1,3-dicarbonyl
      compounds. The electrolytic method employs an organic redox catalyst, which
      obviates the need for oxidizing reagents and transition-metal catalysts. In these
      reactions, the N-allyl amides serve as a four-atom donor to react with dimethyl
      malonate to give pyrrolidines by a (4+1) annulation, or with beta-ketoesters to
      afford tetrahydropyridine derivatives by a (4+2) annulation.

PMID- 30184315
TI  - Brazilin induces T24 cell death through c-Fos and GADD45beta independently
      regulated genes and pathways.
AB  - Purified Brazilin from Sappan wood extract has been reported with significant
      antitumor effect, especially on human T24 cells and bladder cancer mouse models.
      Brazilin can significantly induce expression of c-Fos and GADD45beta and
      transfection expression of c-Fos and GADD45beta in T24 cells can induce
      significant cell morphology changes, reduced viability and cell death, while
      transfection of siRNA-c-Fos and siRNA-GADD45beta can reverse the induced cell
      death. Co-transfection of both c-Fos and GADD45beta into T24 cells resulted in a
      significantly additive effect when compared to single transfection with only c
      Fos or GADD45beta. Meanwhile, transfection of interfering siRNA-c-Fos or siRNA
      GADD45beta can partially rescue the cell viability and siRNA co-transfection
      showed increased rescue rate. The transfection expression and interference with
      pcDNA3.1-c-Fos/siRNA-c-Fos or pcDNA3.1-GADD45beta/siRNA-GADD45beta did not affect
      each other's expression. Moreover, analysis of c-Fos and GADD45beta regulated
      genes and signal pathways showed that no common regulated genes or pathways were
      present. All the results indicated that c-Fos and GADD45beta mediate independent
      Brazilin-inducible genes and pathways. (c) 2018 IUBMB Life, 70(11):1101-1110,
      2018.

PMID- 30184316
TI  - Routine splenic flexure mobilization may increase compliance with pathological
      quality metrics in patients undergoing low anterior resection.
AB  - AIM: Mandatory splenic flexure mobilization (SFM) has been debated for rectal
      cancers. Proponents argue that additional mobilization facilitates a tension-free
      anastomosis; however, this must be weighed against heightened morbidity. Little
      is known about the impact of specific techniques on pathology quality metrics. We
      aim to determine the impact of SFM on pathology quality metrics for patients
      undergoing rectal resections for colorectal adenocarcinoma. METHOD: Patients were
      selected by querying the University of Kansas electronic medical records and the
      American College of Surgeons National Surgical Quality Improvement Program
      database based on Current Procedural Terminology codes. Patients were categorized
      as SFM or non-SFM. Primary outcomes were node yield less than 12 and margin
      length. RESULTS: There were 146 patients who met the inclusion criteria for chart
      review and 7369 included from the national database. Splenic flexure mobilization
      was associated with wider margins (3.52 vs 2.51 cm in low anterior resection, P <
      0.01) and a decreased rate of inadequate nodal staging in patients undergoing low
      anterior resection (3.7% vs 19.3% P < 0.01). CONCLUSIONS: SFM may affect surgical
      quality metrics in patients undergoing resection for distal colon and rectal
      adenocarcinoma. Further study is warranted to determine whether these differences
      in quality and pathology translate into differences in oncological outcomes.

PMID- 30184317
TI  - Can Mitochondrial DNA be CRISPRized: Pro and Contra.
AB  - Mitochondria represent a chimera of macromolecules encoded either in the
      organellar genome, mtDNA, or in the nuclear one. If the pathway of protein
      targeting to different sub-compartments of mitochondria was relatively well
      studied, import of small noncoding RNAs into mammalian mitochondria still awaits
      mechanistic explanations and its functional issues are often not understood thus
      raising polemics. At the same time, RNA mitochondrial import pathway has an
      obvious attractiveness as it appears as a unique natural mechanism permitting to
      address nucleic acids into the organelles. Deciphering the function(s) of
      imported RNAs inside the mitochondria is extremely complicated due to their
      relatively low abundance, which suggests their regulatory role. We previously
      demonstrated that mitochondrial targeting of small noncoding RNAs able to
      specifically anneal with the mutant mitochondrial DNA led to a decrease of the
      mtDNA heteroplasmy level by inhibiting mutant mtDNA replication. We then
      demonstrated that increasing level of expression of such antireplicative
      recombinant RNAs increases significantly the antireplicative effect. In this
      report, we present a new data investigating the possibility to establish a CRISPR
      Cas9 system targeting mtDNA exploiting of the pathway of RNA import into
      mitochondria. Mitochondrially addressed Cas9 versions and a set of
      mitochondrially targeted guide RNAs were tested in vitro and in vivo and their
      effect on mtDNA copy number was demonstrated. So far, the system appeared as more
      complicated for use than previously found for nuclear DNA, because only
      application of a pair of guide RNAs produced the effect of mtDNA depletion. We
      discuss, in a critical way, these results and put them in a broader context of
      polemics concerning the possibilities of manipulation of mtDNA in mammalians. The
      findings described here prove the potential of the RNA import pathway as a tool
      for studying mtDNA and for future therapy of mitochondrial disorders. (c) The
      Authors. IUBMB Life published by Wiley Periodicals, Inc. on behalf of
      International Union of Biochemistry and Molecular Biology, 70(12):1233-1239,
      2018.

PMID- 30184318
TI  - Migratory, metabolic and functional alterations of fibrocytes in type 2 diabetes.
AB  - Fibrocytes are bloodborne mesenchymal progenitor cells that are recruited to
      injured tissue sites and contribute to the repair process by acquiring a
      myofibroblast-like phenotype and producing extracellular matrix components and
      growth factors. Treatment with normal fibrocytes or their exosomes restores the
      ability of genetically diabetic mice to heal skin wounds, suggesting the
      existence of dysfunctional alterations in diabetic fibrocytes. This study
      compared the migratory, metabolic and functional characteristics of fibrocytes
      from patients with type 2 diabetes (T2DPs) and healthy controls (HCs). It was
      found that the frequency of these cells was abnormally low in the peripheral
      blood of T2DPs. Diabetic fibrocytes showed reduced expression of the C-X-C motif
      and C-C motif chemokine receptors (CXCR)4, (CCR)5, and CCR7, and demonstrated
      reduced migration in response to their ligands (CXCL)12, (CCL)5, and CCL21. They
      exhibited increased expression of the receptor for advanced glycation end
      product, suppression of the alternative AGE receptor 1, increased intracellular
      concentrations of AGEs, decreased expression of sirtuin-1 and elevated oxidative
      stress. In short-term cultures, fibrocytes from T2DPs released larger amounts of
      proinflammatory cytokines than those from HCs. Unlike normal fibrocytes, diabetic
      fibrocytes did not exhibit increased expression of type I collagen and alpha
      smooth muscle actin on stimulation with transforming growth factor (TGF)-beta1
      and this abnormal response was associated with downregulation of TGF-beta1 type
      II receptor on the cell surface. Study findings uncover multiple migratory and
      functional alterations of diabetic fibrocytes that may contribute to explain why
      T2DPs experience impaired wound healing and chronic ulcers. (c) 2018 IUBMB Life,
      70(11):1122-1132, 2018.

PMID- 30184319
TI  - Screening of hereditary spherocytosis and pyruvate kinase deficiency by automated
      blood count using erythrocytic and reticulocytic parameters.
AB  - INTRODUCTION: Development of additional parameters for complete blood count has
      emerged in recent hematology analyzers, leading to many publications. However,
      few studies have been conducted on advanced RBC parameters and hemolytic anemias.
      We investigated the interest of Sysmex unique parameters, MicroR and HypoHe, as
      well as the immature fraction of reticulocytes (IRF) in combination with complete
      blood and reticulocyte count, for screening hereditary spherocytosis (HS) and
      pyruvate kinase deficiency. METHODS: We analyzed 182 samples using Sysmex XE-5000
      analyzers from a cohort of red cell disorder patients from the Rouen University
      Hospital. These included 47 HS, 17 pyruvate kinase deficiencies, sickle cell
      diseases and trait, beta-thalassemia minor, iron deficiencies, and 489 samples
      from a routine group. RESULTS: Combining five parameters (hemoglobin level,
      reticulocyte count, IRF, MicroR, and %HypoHe), we developed a specific screening
      tool for HS allowing a sensitivity of 100% and a specificity of 92.1% and a
      specific screening tool for pyruvate kinase deficiencies allowing a sensitivity
      of 100% and a specificity of 96.5%. These parameters were also found accurate in
      infants and in HS without anemia. CONCLUSION: We propose a costless, easy-to-use,
      and efficient approach to detect HS and pyruvate kinase deficiencies using Sysmex
      analyzers. These screening tools may help diagnosis of these disorders, help
      prevent complications, and result in a better management of these patients.

PMID- 30184320
TI  - Automated rare single cell picking with the ALS cellcelectorTM.
AB  - Molecular analysis of rare single cells like circulating tumor cells (CTCs) from
      whole blood patient samples bears multiple challenges. One of those challenges is
      the efficient and ideally loss-free isolation of CTCs over contaminating white
      and red blood cells. While there is a multitude of commercial and non-commercial
      systems available for the enrichment of CTCs their cell output does not deliver
      the purity most molecular analysis methods require. Here we describe the ALS
      CellCelectorTM which can solve this challenge allowing the retrieval of 100% pure
      single CTCs from blood processed by different upstream enrichment techniques. It
      is a multifunctional, extremely flexible system for automated screening of cell
      culture plates, Petri dishes, and microscope slides. Fixed or live single cells
      or multicellular clusters detected during screening can be picked out of those
      plates automatically. The complete scan and picking process is fully documented
      hence allowing highest standardization and reproducibility of all processes. Use
      of CellCelector allowed the isolation of pure single tumor cells or clusters from
      liquid biopsies of breast, prostate, ovarian, colorectal, lung, and brain cancers
      for their subsequent molecular analysis. (c) 2018 The Authors. Cytometry Part A
      published by Wiley Periodicals, Inc. on behalf of International Society for
      Advancement of Cytometry.

PMID- 30184321
TI  - Coronary artery intimal thickening and ventricular dynamics in pediatric heart
      transplant recipients.
AB  - OBJECTIVE: Pediatric heart transplant recipients are at risk of posttransplant
      coronary artery disease known as cardiac allograft vasculopathy (CAV), and also
      may develop diastolic dysfunction. As CAV begins with a process of progressive
      intimal thickening, these occult diffuse changes may be detected using optical
      coherence tomography (OCT). We hypothesized that the development of CAV, as
      identified via OCT, may be a mechanism of declining ventricular function.
      Accordingly, the purpose of this study was to assess coronary artery intimal
      thickening and LV strain in children who have undergone heart transplantation.
      METHODS: In 17 children, we analyzed OCT images for coronary intima and media
      thickness, and cross-sectional area (CSA). We also performed speckle tracking
      imaging (STI) of the LV to determine longitudinal strain and strain rate, in
      addition to standard echocardiographic measures. RESULTS: Longitudinal diastolic
      strain rate was associated with maximum intima thickness (r = -.497, P = .042),
      intima CSA, (r = -.489, P = .047), maximum media thickness (r = -.503, P = .039),
      and media CSA (r = -.614, P = .009). The intima maximum thickness, intima/media,
      and intima/lumen ratios were associated with stroke volume index (Std. beta = 
      0.487, P = .023 and Std. beta = -0.488, P = .022, respectively). CONCLUSIONS:
      These findings suggest coronary artery intimal thickening may be mechanistically
      linked to changes in ventricular function following cardiac transplantation.

PMID- 30184322
TI  - omega-6 and omega-9 polyunsaturated fatty acids with double bonds near the
      carboxyl head have the highest affinity and largest effects on the cardiac IK s
      potassium channel.
AB  - AIM: The IK s channel is important for termination of the cardiac action
      potential. Hundreds of loss-of-function mutations in the IK s channel reduce the
      K+ current and, thereby, delay the repolarization of the action potential,
      causing Long QT Syndrome. Long QT predisposes individuals to Torsades de Pointes
      which can lead to ventricular fibrillation and sudden death. Polyunsaturated
      fatty acids (PUFAs) are potential therapeutics for Long QT Syndrome, as they
      affect IK s channels. However, it is unclear which properties of PUFAs are
      essential for their effects on IK s channels. METHODS: To understand how PUFAs
      influence IK s channel activity, we measured effects on IK s current by two
      electrode voltage clamp while changing different properties of the hydrocarbon
      tail. RESULTS: There was no, or weak, correlation between the tail length or
      number of double bonds in the tail and the effects on or apparent binding
      affinity for IK s channels. However, we found a strong correlation between the
      positions of the double bonds relative to the head group and effects on IK s
      channels. CONCLUSION: Polyunsaturated fatty acids with double bonds closer to the
      head group had higher apparent affinity for IK s channels and increased IK s
      current more; shifting the bonds further away from the head group reduced
      apparent binding affinity for and effects on the IK s current. Interestingly, we
      found that omega-6 and omega-9 PUFAs, with the first double bond closer to the
      head group, left-shifted the voltage dependence of activation the most. These
      results allow for informed design of new therapeutics targeting IK s channels in
      Long QT Syndrome.

PMID- 30184323
TI  - Wear at the taper-trunnion junction of contemporary ceramic-on-ceramic hips shown
      in a multistation hip simulator.
AB  - Ceramic-on-ceramic (CoC) total hip replacements (THR) have a substantially lower
      wear rate than metal-on-polyethylene (MoP) hips, as shown by hip simulator
      testing. However, the revision rates of CoC and MoP hips are comparable. To try
      and explain this discrepancy the wear, at both the bearing surfaces and taper
      trunnion interface of 36 mm BIOLOXdelta CoC THRs, mounted on 12/14 titanium
      (Ti6Al4V) trunnions was investigated using a hip simulator (n = 3) and a
      dynamically loaded CoC sample in a separate test station. Wear was assessed
      gravimetrically and surface roughness measurements of the articulating and taper
      surfaces taken at regular intervals. Scanning electron microscopy, surface
      roughness, and gravimetric measurements of trunnions was performed. After 5
      million cycles, the mean total wear from the ceramic articulating surfaces was
      0.25 mm3 from the hip simulator test, and that from the titanium trunnions was
      0.29 mm3 . This metal wear may provide an explanation for adverse reaction to
      metal debris found in contemporary CoC hip joints. It is therefore vital to
      consider taper-trunnion wear in preclinical testing of artificial hip joints. (c)
      2018 Wiley Periodicals, Inc. J Biomed Mater Res B Part B, 2018.

PMID- 30184324
TI  - The importance of commutability in material used for quality control purposes.
AB  - External Quality Assessment (EQA) is an important part of laboratory quality
      assurance. Spiking of normal plasma is sometimes employed to mimic clinical
      samples. It is important that spiked material gives similar results to clinical
      samples (ie, is commutable) to ensure appropriate conclusions can be drawn from
      EQA exercises. We describe here data from UK National External Quality Assessment
      Scheme for Blood Coagulation (NEQAS BC) exercises where spiked samples were
      tested alongside samples from patients to explore commutability of artificial
      material. Normal plasma was spiked with unfractionated heparin (UFH), low
      molecular weight heparin (LMWH), Dabigatran or Rivaroxaban. Factor VIII (FVIII)
      deficient plasma was spiked with FVIII concentrate. Spiked samples and ex vivo
      patient material were sent to laboratories for testing. For LMWH, good agreement
      was seen between results for samples from patient plasma and plasma spiked with
      heparin. For UFH, APTT ratios differed between spiked and patient samples for the
      same drug concentration, with no correlation in ranking of reagents. Precision
      for patient and spiked material for Rivaroxaban and Dabigatran assays was
      comparable. However, the pattern of results for some Dabigatran assay kits
      differed between spiked and patient samples. For FVIII assays, results obtained
      with spiked and postinfusion samples gave comparable results. Spiked material is
      suitable for EQA if commutability is demonstrated. Our data show commutability
      for plasma spiked with Rivaroxaban, LWMH and some FVIII concentrates. For some
      tests, notably APTT for UFH, marked differences between patient and spiked
      samples indicate not all tests can be evaluated using artificial samples.

PMID- 30184325
TI  - A Matter of Time: The Necessity of Temporal Language in Research on Health
      Conditions that Present with Autism Spectrum Disorder.
AB  - : Relatively consistent findings from recent studies using population-level data
      identify heightened physical and psychiatric morbidity in autistic people
      compared to the general population. Health problems that commonly present with
      autism spectrum disorder (ASD) are generally discussed in the literature as "co
      occurring" or "comorbid" regardless of their known or hypothesized causal
      mechanisms. In this commentary, we introduce a new temporally focused terminology
      to describe health conditions that present with ASD. Emphasizing the temporal
      development of health conditions in research will help the field understand
      whether conditions are (1) "truly co-occurring" (share an etiologic origin with
      ASD in utero and are a defining characteristic of a subphenotype), (2)
      "resulting" (caused by ASD related disparity or the health effect of behaviors
      developed to cope with ASD symptoms), or (3) "associated" (conditions more common
      in individuals with ASD with etiology not yet known or hypothesized, or an
      artifact of diagnostic process or trends). Whether a health condition is "truly
      co-occurring", "resulting", or "associated" has implications for how we design
      interventions to prevent and treat health conditions in people on the autism
      spectrum. Ultimately, we think that using clear and temporally focused language
      can set us on a path to better deduce etiology and develop effective prevention
      and intervention efforts for health conditions that impact the lives of autistic
      individuals. We hope that this approach to temporal language to describe health
      conditions that present with ASD promotes thought and discussion in research,
      advocate, and autistic communities. Autism Res 2018. (c) 2018 International
      Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Research finds
      autistic people have more health problems than the general population but we do
      not understand why. In this commentary, we argue researchers need to use language
      describing the timing of health problems in autistic people, specifying whether
      problems truly co-occur (share a cause), result from autism-related disparities,
      or are more common in autistic people for an unknown reason. Clarifying language
      can provide more specificity in research and improve efforts to prevent and treat
      health problems in autistic people.

PMID- 30184326
TI  - Influence of liquid pore precursors on morphology and mechanical properties of 3D
      scaffolds obtained by dry inversion phase method.
AB  - Polyester 3D scaffolds were obtained by dry inversion phase method. The influence
      of a polymer and liquid pore precursor type on the 3D scaffolds morphology,
      porosity and mechanical properties was tested. Polymers and precursors forming a
      porous structure were identified. It was found that 3D scaffolds having the most
      preferable structure for cell cultures were obtained from polylactide with the
      addition of n-butanol as the liquid pore precursor. (c) 2018 Wiley Periodicals,
      Inc. J Biomed Mater Res B Part B, 2018.

PMID- 30184327
TI  - Bioabsorbable device to prepare subcutaneous pockets for islet transplantation.
AB  - Small invasive transplantation of islets and long maintenance of the islet graft
      without immunosuppression has been studied for the treatment of type 1 diabetes.
      Clinically, subcutaneous pockets surrounding vascular-rich tissue are prepared
      for islet transplantation using a device made of the materials. Here, gelatin
      sheets were implanted into two dorsal subcutaneous sites in diabetic ACI rats,
      and a mixture of bFGF and sodium hyaluronate solution was injected around the
      gelatin sheets. A total of 1500 islets isolated from F344 rats were transplanted
      into each of the pockets 7 days after injection of the bFGF mixture. Nine of 10
      diabetic ACI rats with allogeneic islet graft demonstrated long-term
      normoglycemia without administration of immunosuppressant. Gelatin sheets almost
      disappeared 67 days after implantation. Thus, subcutaneous immune-tolerant sites
      can be prepared using gelatin sheets and a sodium hyaluronate-bFGF mixture.
      Allogeneic islets transplanted into the sites can survive and control blood
      glucose levels for a long period, even without immunosuppression.

PMID- 30184328
TI  - In vitro evaluation of anti-fibrotic effects of select cytokines for vocal fold
      scar treatment.
AB  - Scarring of the vocal fold lamina propria (LP) can cause considerable voice
      disorders due to reduced pliability in scar tissue, attributed in part to
      abnormal extracellular matrix (ECM) deposition produced by the fibrotic vocal
      fold fibroblast (fVFF). Cytokines with anti-fibrotic potential have been
      investigated to limit abnormal LP ECM, but are limited by the need for repeat
      injections. Moreover, the potentially significant role played by activated
      macrophages (AMOs) is usually not considered even though the interaction between
      AMO and fibrotic fibroblasts is known to regulate scar formation across different
      tissues. AMO are also regulated by cytokines that are used for LP scar removal,
      but little is known about AMO behaviors in response to these cytokines within the
      context of LP scar. In the present study, we evaluated anti-fibrotic effects of
      hepatocyte growth factor (HGF), interleukin-10 (IL-10) and interleukin-6 (IL-6)
      in a 3D, in vitro fVFF-AMO co-culture system using poly(ethylene glycol)
      diacrylate (PEGDA) hydrogels. Data from all cytokines was synthesized into a heat
      map that enabled assessment of specific associations between AMO and fVFF
      phenotypes. Cumulatively, our results indicated that both HGF and IL-10 are
      potentially anti-fibrotic (reduction in fibrotic markers and enhancement in
      normal, anti-fibrotic VFF markers), while IL-6 displays more complex, marker
      specific effects. Possible associations between AMO and fVFF phenotypes were
      found and may highlight a potential desirable macrophage phenotype. These data
      support the therapeutic potential of HGF and IL-10 for LP scar treatment, and
      shed light on future strategies aimed at targeting specific AMO phenotypes. (c)
      2018 Wiley Periodicals, Inc. J Biomed Mater Res B Part B: Appl Biomater, 2018.

PMID- 30184329
TI  - Hydroxyproline Attenuates Dextran Sulfate Sodium-Induced Colitis in Mice:
      Involvment of the NF-kappaB Signaling and Oxidative Stress.
AB  - SCOPE: Inflammatory bowel disease (IBD) is a chronic disease of gastrointestinal
      tract in which oxidative stress and overactivation of inflammatory response are
      implicated. The aim of the present study is to test the hypothesis that
      hydroxyproline (Hyp), an amino acid with an antioxidative property, attenuates
      dextran sulfate sodium (DSS)-induced colitis in mice. METHODS AND RESULTS: Male
      C57BL/6 mice supplemented with or without 1% Hyp are subjected to 2.5% DSS in
      drinking water to induce colitis. Hyp attenuates the severity of colitis as
      evidenced by reduced disease activity index scores, decreased myeloperoxidase
      activity, histological damage, and apoptosis. Furthermore, DSS-induced increases
      in reactive oxygen species accumulation, TNF-alpha and IL-6 secretion, and
      malonyldialdehyde activity and a decrease in reduced glutathione in the colon are
      ameliorated by Hyp. The enhanced phosphorylation of STAT3 and NF-kappaB following
      DSS administration is mitigated by Hyp, which is also observed in LPS-treated
      RAW264.7 macrophages. Moreover, the inhibitory effect of Hyp on IL-6 expression
      is mainly mediated by the NF-kappaB signaling, because the induction of STAT3 and
      IL-6 by LPS is markedly reversed by Bay11-7085, a specific inhibitor NF-kappaB.
      CONCLUSION: In summary, Hyp is a critical nutrient with an ability to attenuate
      DSS-induced colonic damage in mice. This beneficial effect of Hyp is partially
      mediated by inhibiting the NF-kappaB/IL-6 signaling and the restoration of redox
      homeostasis.

PMID- 30184330
TI  - Cryopyrin-associated periodic syndrome (CAPS) in a patient with NLRP3 T348M
      mutation.

PMID- 30184331
TI  - Enhancing mechanical properties of an injectable two-solution acrylic bone cement
      using a difunctional crosslinker.
AB  - Two-solution bone cements modified with ethylene glycol-dimethacrylate (EG-DMA)
      as a crosslinker have been developed as an attempt to further improve the
      mechanical properties of acrylic bone cement. The result of this study shows that
      EG-DMA can increase the mechanical properties and fractional monomer conversion
      while preserving the thermal characteristics. The strength and bending modulus
      increase with EG-DMA concentrations at 5-10 vol % EG-DMA. Substituting the EG-DMA
      content past 10 vol % decreases the bending properties due to the effects of
      reduced monomer concentrations. Strengthened EG-DMA samples demonstrated an
      increase in ductility with noticeably different fracture surface morphologies
      than the control samples, indicated by microtroughs and ridge formation caused by
      excessive plastic strain. This work provides insight into the effect of
      substituting a crosslinker for MMA monomer in an injectable two-solution system
      and lays out the ideal concentrations of EG-DMA for superior mechanical or
      fractional monomer conversion properties. (c) 2018 Wiley Periodicals, Inc. J.
      Biomed. Mater. Res. Part B, 2018.

PMID- 30184333
TI  - The use of electrochemical techniques to evaluate the corrosion performance of
      metallic biomedical materials and devices.
AB  - The corrosion performance of metallic biomedical materials and devices is
      commonly evaluated using electrochemical techniques. Although test standards
      involving such techniques have been released to address some forms of corrosion,
      a key issue is application of the results with regard to use of an implantable
      device in vivo. This review focuses on nitinol, 316L/LVM stainless steel, and Co
      Cr alloys and is intended to provide some perspective on the significance of
      results from tests concerning general corrosion, localized corrosion, galvanic
      corrosion, and fretting corrosion of these alloys in simulated physiological
      solutions. It also examines the factors that could cause differences in the
      corrosion performance between in vitro and in vivo exposure, with the goal of
      providing some rationale for applying electrochemical characteristics obtained
      from the tests to predict the corrosion performance in vivo. (c) 2018 Wiley
      Periodicals, Inc. J Biomed Mater Res B Part B: Appl Biomater, 2018.

PMID- 30184332
TI  - A test method to assess the contribution of fluid shear stress to the cleaning of
      reusable device surfaces.
AB  - Adequate cleaning of reusable medical devices is critical for preventing cross
      infection among patients. For reusable medical devices, cleaning using mechanical
      brushes and detergent may not be sufficient to completely remove the infectious
      contaminants from the surfaces. This study evaluates the role of fluid flow
      induced shear stress in the detachment and removal of contaminants from device
      surfaces. A stainless-steel test coupon, acting as a surrogate for a device
      surface, was coated with artificial clot of varying mass. The test coupon was
      exposed to fluid shear stress both with and without an enzymatic detergent. The
      relationship between clot removal quantity and the applied shear stress was
      obtained for multiple clot masses. Our results showed that fluid shear increased
      the effectiveness of the cleaning process. In the absence of flow, soaking the
      clot surface in the enzymatic detergent removed 67%, 77%, and 95% of the clot for
      16 mg, 6.8 mg, and 1 mg initial masses, respectively. In the presence of fluid
      shear (0.3 Pa for 5 min), approximately 85%, 97%, and 99% of the clot was removed
      from the surface. The clot mass removed followed a linear relationship (R2 =
      0.98) versus the applied fluid shear stress. This study showed that different
      cleaning processes such as fluid shear and detergent action contribute to the
      soil removal process. This method could be used to evaluate cleaning protocols
      for minimizing contaminant residue after the reprocessing of medical devices.

PMID- 30184334
TI  - Long-term outcomes and quality of life following ligation of the intersphincteric
      fistula tract for high transsphincteric fistulas.
AB  - AIM: Published outcomes following ligation of the intersphincteric fistula tract
      (LIFT) for high transsphincteric fistulas (HTFs) are equivocal probably because
      most trials are small and comprise mixed patient populations. The aim of this
      study was to highlight the long-term efficacy of LIFT for HTFs in a large
      homogeneous sample and to determine the risk factors that contribute to non
      healing resulting in failure and recurrence. METHOD: A retrospective study was
      performed which assessed patients with HTFs treated by LIFT without prior loose
      setons from September 2012 to December 2017. Continence function was evaluated by
      the Wexner incontinence scale and anal manometry. Quality of life was assessed by
      using the faecal incontinence quality of life (FIQL) scale with four domains:
      lifestyle, coping, depression and embarrassment. RESULTS: Seventy patients with
      HTFs underwent 71 LIFT procedures. The primary healing rate was 81.7% with a
      median follow-up duration of 16.5 (range 4.5-68) months. The healing rates of
      mature and immature fistulas were 83.7% and 77.3%, respectively. Two patients
      suffered failure with an unhealed intersphincteric wound. Recurrence occurred in
      11 patients. Incontinence of flatus, present in four patients before surgery,
      improved postoperatively. Two patients undergoing LIFT combined with fistulotomy
      complained of flatus incontinence after surgery. No significant differences
      between preoperative and postoperative Wexner score, maximum resting pressure and
      maximum squeeze pressure were detected. The FIQL was improved in lifestyle,
      coping and depression. No risk factor for non-healing was found. CONCLUSION: LIFT
      has a promising long-term outcome for HTFs, with negligible impairment on
      continence and improved quality of life.

PMID- 30184335
TI  - Intra-operative fluorescence angiography facilitates tailored resection in
      ischaemic colitis - a video vignette.

PMID- 30184336
TI  - Exploring changes in oral hygiene behaviour in patients with diabetes and
      periodontal disease: A feasibility study.
AB  - OBJECTIVE: Exploring the feasibility to understand changes in oral hygiene
      behaviour using the Health Action Process Approach (HAPA) model applied to
      qualitative research interviews in patients with diabetes and periodontitis
      undergoing standard periodontitis treatment. METHODS: Patients with type 1/2
      diabetes and chronic periodontitis (n = 8) received standard non-surgical
      periodontal treatment accompanied with personalized oral hygiene instructions by
      a dental hygienist. Clinical indices (% bleeding on probing (BOP), probing depth
      (PD), clinical attachment level (CAL), % of sites with PD >= 5 mm, periodontal
      epithelial surface area (PESA) and periodontal inflammatory surface area (PISA)
      were recorded pre- and post-treatment. At 3 months post-treatment, patients were
      interviewed using a topic guide relating to oral health. A behaviour change
      framework was constructed from elements of the HAPA model and used directly to
      map interview data to evaluate oral hygiene behaviour in these patients. RESULTS:
      Data from this feasibility study suggest a clinical improvement in periodontal
      status, albeit only monitored for 3 months. Application of the HAPA model
      highlighted the behavioural change pathway that diabetes patients undertake
      before, during and after periodontal treatment. The data suggest that patients
      move through all elements of the motivation phase and all elements of the
      volition phase except for the recovery self-efficacy element. CONCLUSION: The
      novel approach of applying the HAPA model to qualitative research data allowed
      for the collection of richer data compared to quantitative analysis only.
      Findings suggest that, in general, patients with periodontitis and diabetes
      successfully manage to incorporate new oral hygiene behaviours into their daily
      routine.

PMID- 30184337
TI  - Tolerogenic Iron Oxide Nanoparticles in Type 1 Diabetes: Biodistribution and
      Pharmacokinetics Studies in Nonobese Diabetic Mice.
AB  - Nanoparticle (NP) administration is among the most attractive approaches to
      exploit the synergy of different copackaged molecules for the same target. In
      this work, iron oxide NPs are surface-engineered for the copackaging of the
      autoantigen proinsulin, a major target of adaptive immunity in type 1 diabetes
      (T1D), and 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methylester
      (ITE), a small drug conditioning a tolerogenic environment. Magnetic resonance
      imaging (MRI) combined with magnetic quantification are used to investigate NP
      biokinetics in nonobese diabetic (NOD) mice and control mice in different organs.
      Different NP biodistribution, with in particular enhanced kidney elimination and
      a stronger accumulation in the pancreas for prediabetic NOD mice, is observed.
      This is related to preferential NP accumulation in the pancreatic inflammatory
      zone and to enhancement of renal elimination by diabetic nephropathy. For both
      mouse strains, an MRI T2 contrast enhancement at 72 h in the liver, pancreas, and
      kidneys, and indicating recirculating NPs, is also found. This unexpected result
      is confirmed by magnetic quantification at different time points as well as by
      histological evaluation. Besides, such NPs are potential MRI contrast agents for
      early diagnosis of T1D.

PMID- 30184339
TI  - Long-term outcomes following sweat gland excision for axillary hyperhidrosis.

PMID- 30184338
TI  - Identification of a Novel Function of Resveratrol and Genistein as a Regulator of
      beta2 -Adrenergic Receptor Expression in Skeletal Muscle Cells and
      Characterization of Promoter Elements Required for Promoter Activation.
AB  - SCOPE: Modulating beta2 -adrenergic receptor (beta2 -AR) expression and
      activation is important for maintaining skeletal muscle function. In this study,
      two food factors, resveratrol (RSV) and genistein (GEN), that are able to
      regulate beta2 -AR promoter activity and may improve skeletal muscle function are
      identified. METHODS AND RESULTS: Using luciferase reporter assay, 357 functional
      food factors as candidates for beta2 -AR promoter activity have been screened and
      subsequently RSV and GEN increase beta2 -AR promoter activity and beta2 -AR mRNA
      expression. Using promoter sequence analysis, it is shown that the CCAAT box and
      the GC box on the beta2 -AR promoter are required for the regulation of beta2 -AR
      expression by RSV or GEN. It is also ascertained that transcription factor NF-YA
      binds to the CCAAT box on the beta2 -AR promoter and that the amount of NF-YA
      bound to the CCAAT box is unchanged by RSV or GEN treatment. Finally, it is
      confirmed that a GEN-containing diet increases beta2 -AR expression in mouse
      skeletal muscle and increased skeletal muscle mass. CONCLUSIONS: The findings
      show that food-derived molecules have the potential to influence skeletal muscle
      mass and function by regulating G protein-coupled receptor expression.

PMID- 30184340
TI  - MSC-Seeded Biomimetic Scaffolds as a Factory of Soluble RANKL in Rankl-Deficient
      Osteopetrosis.
AB  - Biomimetic scaffolds are extremely versatile in terms of chemical composition and
      physical properties, which can be defined to accomplish specific applications.
      One property that can be added is the production/release of bioactive soluble
      factors, either directly from the biomaterial, or from cells embedded within the
      biomaterial. We reasoned that pursuing this strategy would be appropriate to
      setup a cell-based therapy for RANKL-deficient Autosomal Recessive Osteopetrosis,
      a very rare skeletal genetic disease in which lack of the essential
      osteoclastogenic factor RANKL impedes osteoclast formation. The exogenously
      administered RANKL cytokine is effective in achieving osteoclast formation and
      function in vitro and in vivo, thus, we produced murine Rankl-/- MSCs
      overexpressing human soluble RANKL (hsRL) following lentiviral transduction
      (LVhsRL). Here, we described a three-dimensional (3D) culture system based on a
      Magnesium-doped hydroxyapatite/collagen I (MgHA/Col) biocompatible scaffold
      closely reproducing bone physicochemical properties. MgHA/Col-seeded murine MSCs
      showed improved properties, as compared to two-dimensional (2D) culture, in terms
      of proliferation and hsRL production, with respect to LVhsRL-transduced cells.
      When implanted subcutaneously in Rankl-/- mice, these cell constructs were well
      tolerated, colonized by host cells, and intensely vascularized. Of note, in the
      bone of Rankl-/- mice that carried scaffolds with either WT or LVhsRL-transduced
      Rankl-/- MSCs, we specifically observed formation of TRAP+ cells, likely due to
      sRL released from the scaffolds into circulation. Thus, our strategy proved to
      have the potential to elicit an effect on the bone; further work is required to
      maximize these benefits and achieve improvements of the skeletal pathology in the
      treated Rankl-/- mice. Stem Cells Translational Medicine 2018.

PMID- 30184341
TI  - MetScore: Site of Metabolism Prediction Beyond Cytochrome P450 Enzymes.
AB  - The metabolism of xenobiotics by humans and other organisms is a complex process
      involving numerous enzymes that catalyze phase I (functionalization) and phase II
      (conjugation) reactions. Herein we introduce MetScore, a machine learning model
      that can predict both phase I and phase II reaction sites of drugs in a single
      prediction run. We developed cheminformatics workflows to filter and process
      reactions to obtain suitable phase I and phase II data sets for model training.
      Employing a recently developed molecular representation based on quantum chemical
      partial charges, we constructed random forest machine learning models for phase I
      and phase II reactions. After combining these models with our previous cytochrome
      P450 model and calibrating the combination against Bayer in-house data, we
      obtained the MetScore model that shows good performance, with Matthews
      correlation coefficients of 0.61 and 0.76 for diverse phase I and phase II
      reaction types, respectively. We validated its potential applicability to lead
      optimization campaigns for a new and independent data set compiled from recent
      publications. The results of this study demonstrate the usefulness of quantum
      chemistry-derived molecular representations for reactivity prediction.

PMID- 30184342
TI  - The challenges of health situation analysis in Colombia.
AB  - General and local health situation analyses have increasingly become a political
      issue with implications for the population under study and for decision makers,
      as it involves the spheres of power, and entails economic, social and cultural
      responsibilities.As an essential function of public health, health situation
      analysis has assessment parameters that make it possible to direct its
      development and measure its implications. This is where the first challenge lies.
      However, the most important ones go beyond the technical criteria established in
      the year 2000 by the Pan American Health Organization.The local dynamics where
      health situation analyses are inscribed, are increasingly more influenced by
      globalization processes, which in turn demand that international policies be
      articulated in our country, as is the case with the Sustainable Development
      Goals. Moreover, the demographic and epidemiological transition requires
      accounting for heterogeneous profiles including mental, occupational and
      environmental health.In addition, complexity increases in a context like ours,
      with deep inequalities that should be addressed within the framework of the
      Social Security System, which imply challenges in terms of knowledge, technical
      aspects, articulation, context, coherence, and policies.

PMID- 30184343
TI  - First record of the sand fly Warileya (Hertigia) hertigi from Antioquia, Colombia
AB  - Introduction: The genus Warileya is one of the least-known taxa of sandflies,
      comprising only nine species, i.e., W. (Warileya) phlebotomanica, W. (Hertigia)
      hertigi, W. (W.) rotundipennis, W. (W.) nigrosacculus, W. (W.) yungasi, W. (W.)
      fourgassiensis, W. (W.) lumbrerasi, W. (W.) euniceae and W. (W.)
      leponti.Objective: To document the presence of a species of the genus Warileya in
      Antioquia, Colombia. Materials and methods: Sandflies were collected in a cavern
      of the Canon del Rio Claro Natural Reserve, of the municipality of San Francisco,
      Antioquia department, Colombia. Phlebotomine sampling was carried out using a CDC
      light trap during three consecutive nights in May of 2008. Taxonomical
      determination was based on a revision of the type material of the species and
      through the use of standard keys for American sandflies.Results: Five male and
      two female sandflies were taxonomically identified as W. (H.) hertigi. In both
      sexes, the absence of setal scars in the anepisternum, proepimeron and clypeus;
      the presence of two transverse rows of setal scars in the tergites; and the short
      length of the vena gamma were notable. Conclusion: The finding of W. (H.) hertigi
      increases the number of sandfly species found in Antioquia department to 64. In
      total, 164 sandfly species have been recorded in Colombia.

PMID- 30184344
TI  - Reporting of statistical regression analyses in Biomedica: A critical assessment
      review
AB  - Introduction: Regression modeling is a statistical method commonly used in health
      research, especially by observational studies.Objective: The objectives of this
      paper were to 1) determine the frequency of reporting of regression modeling in
      original biomedical and public health articles that were published in Biomedica
      between 2000 and 2017; 2) describe the parameters used in the statistical models,
      and 3) describe the quality of the information reported by the studies to explain
      the statistical analyses.Materials and methods: We conducted a critical
      assessment review of all original articles published in Biomedica between 2000
      and 2017 that used regression models for the statistical analysis of the studies
      main objectives. We generated a 20-item checklist based on four good practice
      guidelines for the presentation of statistical methods.Results: Most of the
      studies were observational studies related to public health sciences (65.7%).
      Less than half (37.2%) of them reported using a combination of conceptual
      frameworks and statistical criteria for the selection of variables to be included
      in the regression model. Less than one quarter (22.1%) reported the verification
      of the assumptions of the model. The most frequently used uncertainty measure was
      the p-value (73.5%).Conclusion: There are significant limitations in the quality
      of the reports of statistical regression models, which reviewers and readers need
      in order to correctly assess and interpret the statistical models. The results,
      herein, are provided as an invitation to researchers, reviewers, and editors of
      biomedical journals to develop, promote, and control an appropriate culture for
      statistical analysis and reporting in Colombia.

PMID- 30184345
TI  - [A case series of pure neural leprosy in patients diagnosed in a specialized
      center for the control of Hansen's disease in Colombia].
AB  - Pure neural leprosy, defined as a peripheral neuropathy in which the patient has
      no skin lesions, is difficult to diagnose. Its verification by bacteriological
      index and histopathology is not possible in the majority of the patients.We
      describe four cases of pure neural leprosy diagnosed by clinical criteria. The
      clinical outcome of three of the patients after specific treatment was
      satisfactory, while the other one developed progressive neural damage despite the
      therapy. All patients were treated in a specialized center for the management and
      control of Hansen's disease in the municipality of Contratacion, Santander,
      Colombia.

PMID- 30184346
TI  - [Developmental stages and viability of Toxocara canis eggs outside the host].
AB  - INTRODUCTION: Toxocariasis is a soil-transmitted zoonotic disease caused mainly
      by ingestion of larvated eggs of Toxocara canis. OBJECTIVES: To study the
      morphology of the intraovular developmental stages of Toxocara canis in culture,
      characterize non-viable eggs and the sequences of larval molting and compare the
      viability of eggs at the early stages of division and at reaching full
      maturation. MATERIAL AND METHODS: Observation of developing embryos and
      characterization of non-viable eggs were done using light microscope. The
      proportions of viable eggs during embryonation were compared to the proportions
      of viable mature eggs. RESULTS: Cell division commenced after 24 hours of
      cultivation. Early stages were found to be present over a period of 3-5 days. The
      developmental stages identified were eggs with: One cell, two cells, three cells,
      four cells, early morula, late morula, blastula, gastrula, tadpole, pre-larva,
      first, second and third stage larva. Two larval molts occurred. Non-viable eggs
      had degenerated cytoplasm, thin or collapsed shell and the larvae did not move
      after exposure to light. No significant differences were found between the
      proportions of viable eggs from day five to day 21 as compared to viability of
      fully mature eggs (30 days). CONCLUSION: Developing embryos in the environment
      may be considered as a potential threat to the public health. The precise
      identification of developmental stages and the clear differentiation of viable
      and non-viable eggs can help in determining an accurate baseline rate of
      development that could be used in studies of ovicidal compounds.

PMID- 30184347
TI  - [Tuberculosis and comorbidities in urban areas in Argentina. A gender and age
      perspective].
AB  - INTRODUCTION: Tuberculosis continues to be a major health problem in the world
      with an incidence of more than 10 million cases in 2015. There are factors that
      change the risk of developing the disease after infection, as well as the
      presentation of the disease. OBJECTIVE: To determine the main comorbidities and
      demographic, clinical and microbiological characteristics of tuberculosis adult
      patients in Argentina from a gender and age perspective. MATERIALS AND METHODS:
      We conducted a cross-sectional study in urban referral hospitals for patients
      with tuberculosis. We included tuberculosis patients of 15 years or more of age
      who were hospitalized or treated in outpatient clinics with bacteriologically
      confirmed pulmonary or extrapulmonary forms of the disease, as well as those who,
      although not bacteriologically confirmed, had clinical and radiological
      characteristics consistent with tuberculosis. The study period was from August
      1st, 2015 to August 31st, 2016. RESULTS: We included 378 patients. The median age
      was 37 years. Male gender was associated with extrapulmonary tuberculosis,
      hospitalization, smoking, drug addiction and alcoholism. Tuberculosis and aids
      (22.6%) was related to drug use, admission into hospital, extrapulmonary
      tuberculosis, nonaddiction to tobacco, non-pathological radiology, absence of
      cavitation, and negative sputum smear microscopy. Patients less than 40 years of
      age had a higher rate of drug addiction and low weight, while those aged 40 or
      over had a higher proportion of diabetes, alcoholism and chronic obstructive
      pulmonary disease (COPD). CONCLUSIONS: This study will help recognize
      tuberculosis patients' characteristics and comorbidities influencing the
      development and evolution of the disease from an age and gender perspective to
      enable the development of social and community-based strategies.

PMID- 30184348
TI  - Rare diseases mortality in Colombia, 2008-2013
AB  - Introduction: Rare diseases are characterized by their low prevalence, often of
      genetic origin, degenerative and life threatening.Objective: To describe
      mortality by orphan diseases and to analyze its trends in Colombia from 2008 to
      2013.Materials and methods: We conducted a descriptive study to analyze mortality
      rate trends from the death certificates between 2008 and 2013. We calculated
      specific mortality rates and adjusted by age and sex.Results: Seven thousand one
      hundred and thirty five deaths were attributed to orphan diseases, and 51.4 % of
      them occurred among men of all ages. The mean mortality rate during the study
      period was 2.53 deaths per 100,000 people. Overall, the trend showed an
      increasing pattern of mortality although very heterogeneous across the country.
      Mortality rates were higher in Bogota (20), and the Andes and the Caribbean
      regions (5.3 and 3.7 deaths per 100,000 population). The five most important
      causes of mortality among men were: acute lymphoblastic leukemia, muscular
      dystrophy, bronchopulmonary dysplasia originating in the perinatal period,
      multiple sclerosis, Guillain-Barre syndrome and gastroschisis, and among women:
      multiple sclerosis, acute lymphoblastic leukemia, gastroschisis, bronchopulmonary
      dysplasia originating in the perinatal period, Guillain-Barre syndrome and acute
      myeloid leukemia. The mean mortality rate by acute lymphoblastic leukemia was
      0.17 deaths per 100,000 men younger than 15 years and that of multiple sclerosis
      was 0.16 in women over 40 years of age.Conclusion: The causes of death showed a
      similar pattern in both sexes. However, the burden of mortality was higher among
      men of all ages in Bogota.

PMID- 30184349
TI  - Neuroanatomical evidence of the transport of the rabies virus through the
      propriospinal tract in the spinal cord of mice
AB  - Introduction: Information about the neuroanatomical details of the ascendant
      transport of the rabies virus through the spinal cord is scarce.Objective: To
      identify the neuroanatomical route of dissemination of the rabies virus at each
      of the levels of the spinal cord of mice after being inoculated
      intramuscularly.Materials and methods: Mice were inoculated with the rabies virus
      in the hamstrings. After 24 hours post-inoculation, every eight hours, five
      animals were sacrificed by perfusion with paraformaldehyde. Then, the spinal cord
      was removed, and transverse cuts were made at the lumbosacral, thoracic, and
      cervical levels. These were processed by immunohistochemistry for the detection
      of viral antigens.Results: The first antigens of rabies were observed as
      aggregated particles in the lumbar spinal cord at 24 hours post-inoculation,
      within the ventral horn in the same side of the inoculated limb. At 32 hours post
      inoculation the first motoneurons immunoreactive to the virus became visible. At
      40 hours postinoculation the first immunoreactive neurons were revealed in the
      thoracic level, located on lamina 8 and at 48 hours post-inoculation in the
      cervical cord, also on lamina 8. At 56 hours post-inoculation the virus had
      spread throughout the spinal cord, but the animals still did not show signs of
      the disease. Conclusion: In the mouse model we used, the rabies virus entered the
      spinal cord through the motoneurons and probably used the descending
      propriospinal pathway for its retrograde axonal transport to the encephalus.

PMID- 30184350
TI  - Etiological identification of viral agents in acute encephalitis in Guadalajara,
      Mexico, 2011-2015
AB  - Introduction: Viral encephalitis is a well-known inflammatory process associated
      with neurological dysfunction that might derive into severe brain damage or a
      fatal outcome. In Mexico there is no epidemiological data that describes the
      prevalence of viral agents responsible for acute encephalitis.Objective: To
      identify the main viral agents by real time PCR involved in acute encephalitis in
      Mexico.Materials and methods: We obtained cerebral spinal fluid (CSF) samples
      from all patients with suspected viral encephalitis admitted to the emergency
      service of the Hospital Civil de Guadalajara "Fray Antonio Alcalde". To identify
      pathogens, we performed nucleic acid extraction using real-time PCR and RT
      PCR.Results: Sixty-six patients were diagnosed with acute encephalitis from 2011
      to 2014. A definitive viral etiological diagnosis was established in 16 patients
      (24%); the main causative agents were enteroviruses in 50% of the 16 positive
      samples, followed by herpes simplex virus (37%) and cytomegaloviruses (12.5%).
      Patients with encephalitis were predominantly male (63.3%) and a seasonal
      predominance was observed during autumn (37.5%). The main clinical
      characteristics in the acute encephalitis phase were fever (48.45) and cephalea
      (36.3), followed by seizures, disorientation, and muscular weakness (30.3%).
      Kerning sign was present in two cases (3%) and other two cases presented
      Brudzinski's sign (3%).Conclusions: CSF PCR is a suitable diagnostic technique
      for the identification of viral encephalitis caused by viral infections that
      allows an appropriate antiviral therapeutic treatment.

PMID- 30184351
TI  - Performance of molecular methods for identification of unusual subtypes of
      hepatitis C virus genotype 2
AB  - Introduction: Hepatitis C virus (HCV) displays high genetic variability, with
      seven genotypes and numerous subtypes. The determination of the viral type has
      been essential for the selection and timing of antiviral treatment. In Venezuela,
      HCV genotype 2 is relatively diverse, being particularly prevalent subtype
      2j.Objective: To evaluate the performance of methodologies for genotyping HCV,
      particularly for identification of subtype 2j.Materials and methods: HCV genotype
      and subtype were determined by reverse hybridization technique (LiPA) and
      sequencing of the HCV 5'UTR and NS5B regions.Results: A total of 65 samples from
      HCV-infected patients were analyzed. PCR amplifications of the 5'UTR region
      exhibited the highest sensitivity (100% vs 91% for LiPA and 77% for NS5B).
      Genotype determination, taking as reference test NS5B, showed 100% concordance
      with the other methods, and 67% and 59% for subtypes with 5'NC and LiPA,
      respectively. NS5B sequencing allowed the identification of subtypes 2j and 2s,
      which were not detected by the other methods. A specific LiPA pattern was
      notobserved for HCV subtype 2j.Conclusion: Although being the methodology with
      lowest sensitivity for amplification of HCV RNA, sequencing NS5B region remains a
      powerful tool for correct discrimination of the different HCV subtypes, which is
      of epidemiological relevance.

PMID- 30184352
TI  - Levels of physical activity, health-related quality of life, physical self
      concept and body-mass index among Colombian students
AB  - Introduction: Physical activity, health-related quality of life, self-concept and
      body-mass index are indicators of a healthy lifestyle.Objective: To determine the
      levels of physical activity and sedentary lifestyle, the health-related quality
      of life, the physical self-concept and the body-mass index in Colombian middle
      and highschool students.Materials and methods: We included 1,253 students between
      10 and 20 years of age (601 men and 652 women) in the study. We used the
      following instruments for the measurements: A weighing machine, a stadiometer,
      the International Physical Activity Questionnaire, the 12-Item Short Form Health
      Survey (SF-12(r)), and the Physical Self-concept Questionnaire in its Spanish
      version.Results: The statistical analysis showed higher levels in the body-mass
      index among female students and higher scores for the physical condition, self
      concept and competence among male students, with meaningful statistical
      differences (p<0,05). Additionally, women had higher scores in moderate and
      vigorous physical activity, while men had higher scores in walking. Men got
      higher scores in the dimension of health-related quality of life, except in the
      social function, which differed significantly from the general health, emotional
      role, mental health, and vitality dimensions.Conclusions: We found a relation
      between the body-mass index and the physical condition and competence self
      concept, as well as between body-mass index and general health, physical
      function, mental health and vitality. We also found a relation between a
      sedentary lifestyle and general health, body pain, and physical role.

PMID- 30184353
TI  - Specific IgY anti-group 1 dust mite allergens induced by unglycosylated synthetic
      oligopeptides
AB  - Introduction: The use of specific antibodies capable of detecting allergens of
      the group 1 of house dust mites represents a potential strategy to reduce
      exposure and clinical symptomatology associated with asthma and allergic
      rhinitis.Objective: To produce and purify chicken antibodies specific for the
      dust mites Dermatophagoides sp. and B. tropicalis using the IgY
      technology.Materials and methods: We designed and synthesized oligopeptides
      showing immunogenic epitopes of Der p1, Der f1, and Blo t1. These were used to
      produce IgY antibodies in Hy Line Brown chickens. IgY were extracted from egg
      yolk using thiophilic chromatography. The immunogenicity and specificity were
      assayed by indirect ELISA and Dot Blot.Results: We obtained high reactivity of
      IgY antibodies against epitopes of allergens present in whole body mites extracts
      of D. farinae, D. pteronyssinus, and B. tropicalis. The highest IgY levels were
      registered between days 32 and 40 after immunization. The antibodies showed high
      immunoreactivity and specificity towards D. farinae proteins with detection
      limits above 0.03 MUg of mite proteins under the experimental conditions used.
      Purified IgY did not show significant reactivity when binding to Periplaneta
      americana extract.Conclusion: The IgY technology allowed the production of
      specific antibodies against house dust mites group 1 allergens using non
      glycosylated synthetic peptides. To our knowledge, this is the first time that
      this immunochemicals are used in the detection of mites of medical relevance.

PMID- 30184354
TI  - Comparison of methodologies for microscopic malaria diagnosis
AB  - Introduction: As part of the pre-elimination plan for malaria in Colombia, it has
      been proposed to develop activities within the line of work: "Improve access and
      quality of malaria diagnosis".Objective: To compare the methodology recommended
      by PAHO/WHO with that used in Colombia for the diagnosis of malaria.Materials and
      methods: Samples were collected and 88 slides were prepared for malaria
      diagnosis, under different scenarios according to the parameters to be evaluated.
      After duplicate mycroscopic reading, the respective variance calculations were
      performed for all possible staining comparisons with the two methods used (thick
      smear, combined thick smear), according to the staining (modified Romanowsky or
      Giemsa), with the result variable being the parasite density (500, 1,000, 5,000
      and 10,000 parasites/MUl of blood).Results: A Cohen kappa index of inter-rater
      agreement of 0.923 (95% CI: 0.768-1.078) was obtained. None of the factors (A:
      stain, B: methodology) or interactions (AB) had a statistically significant
      effect on the results with a 95% confidence level.Conclusion: Based on the
      results of the study, the preparation of two thick smears in the same slide
      stained with the modified Romanowsky stain is a suitable methodology for the
      diagnosis of malaria in Colombia, due to its technical characteristics, of
      storage, low cost, use and care.

PMID- 30184355
TI  - Effectiveness of knowledge translation and knowledge appropriation of clinical
      practice guidelines for patients and communities, a systematic review
AB  - Introduction: Knowledge translation and knowledge appropriation social
      interventions apply knowledge to improve health services and outcomes. These
      interventions can be implemented routinely to improve patient adherence to
      clinical practice guidelines.Objective: To assess the effectiveness of knowledge
      translation interventions to improve patient and community adherence to clinical
      practice guidelines.Materials and methods: We performed a systematic review of
      these interventions compared with classical interventions for patients and/or
      communities. We searched the following electronic databases up to April 2017:
      Medline (Ovid), Embase, Scopus, Central (Ovid), Web of Science, LILACS, Academic
      Search, and Scielo. Two independent raters qualified the relevance, risk of bias,
      and quality of included studies.Results: Eight studies were included. Patient
      adherence to recommendations was observed in two studies. There was high
      heterogeneity due to the variability of the population, types of guidelines, and
      types of measurement tools. The risk of bias was high: a 60% risk of performance
      bias, 50% risk of attrition bias, 25% risk of selection and reporting bias, and
      15% risk of detection bias. The quality of evidence was moderate for the outcomes
      of adherence and mortality. The interventions that used a combination of
      strategies, such as with the group of health professionals, could improve some
      clinical outcomes in the patients (Average deviation: -3.00; 95% IC: -6.08
      0.08).Conclusions: Knowledge translation interventions might have a slight
      positive effect on patient adherence and some short-term clinical outcomes,
      particularly within mixed interventions (patients and health professionals).
      However, future studies with less heterogeneity are necessary to confirm these
      results.

PMID- 30184356
TI  - Genetic variability of Aedes aegypti in the department of Sucre, Colombia, by
      analysis of the nucleotide sequence of the mitochondrial ND4 gene
AB  - Introduction. Aedes aegypti is the most important mosquito species in America for
      the transmission of viruses of dengue, Zika, Chikungunya and yellow fever.
      Ecological factors as well as chemical controls can affect the genetic
      composition of Ae. aegypti populations, which is why its genetic characterization
      is necessary.Objective. To determine the genetic variability of Ae. aegypti
      populations in four municipalities of Sucre department, Colombia.Materials and
      methods. Larvae of Ae. aegypti, collected in the municipalities of Sincelejo,
      Sampues, Corozal and Guaranda, Sucre department, were reared under laboratory
      conditions to adult stage. A segment of the mitochondrial ND4 gene which codes
      for the subunit 4 of the enzyme NADH-dehydrogenase was used as genetic marker.
      The genetic analysis included the estimation of parameters of nucleotide and
      haplotype diversity, genetic structure and gene flow.Results. One hundred and
      eight partial sequences of 357 nucleotides and four nucleotide haplotypes of the
      ND4 gene of Ae. aegypti were obtained. A significantly high genetic
      differentiation was found between the Sampues and Guaranda populations
      (FST=0.59467), Sincelejo and Sampues (FST=0.25637), and Corozal and Guaranda
      (FST=0.22237). A high gene flow (Nm=infinite) was observed among the populations
      of Sincelejo and Corozal.Conclusion. There are genetic differences between the
      Ae. aegypti populations from the municipalities of Sucre department. The presence
      of a new haplotype of the mitochondrial ND4 gene of Ae. aegypti in Colombia was
      recorded, detected in the municipality of Sincelejo.

PMID- 30184357
TI  - Congenital cerebral toxoplasmosis, Zika and chikungunya virus infections: a case
      report
AB  - We report a case of intrauterine infection by Toxoplasma gondii, Chikungunya and
      Zika viruses in a Colombian woman from the southern part of the country. The
      patient attended prenatal care in the second trimester of her pregnancy and she
      informed that in the first trimester she had presented with clinical symptoms
      compatible with Zika virus infection. Amniotic fluid PCR assays showed infection
      by T. gondii, chikungunya and Zika viruses. Diagnostic imaging showed fetal
      malformation of the central nervous system. At 29 weeks of gestation, pregnancy
      was terminated medically.

PMID- 30184358
TI  - Health economics and public health: Global situation and local perspectives

PMID- 30184359
TI  - Molecular detection of Salmonella spp., Listeria spp. and Brucella spp. in fresh
      artisanal cheese marketed in the city of Barranquilla: A pilot study
AB  - Introduction: Each year approximately 3 million people die as the result of
      foodborne diseases. The fresh artisan (handmade) cheese produced and distributed
      in the Colombian Caribbean region is a native product from the departments of
      Cordoba, Sucre, Bolivar, Atlantico, Magdalena, Cesar, and La Guajira. Its mass
      consumption increases the risk of infection with Salmonella spp., Listeria spp.,
      and Brucella spp., as it is made with a very rustic technology, with
      unpasteurized cow milk, without standardized and hygienic procedures and its
      storage is inadequate.Objective: To detect the presence of Salmonella spp.,
      Listeria spp., and Brucella spp. in samples of fresh artisan cheese from the
      Colombian Caribbean region.Materials and methods: Twenty-seven samples of cheese
      from five departments of the Caribbean Region (Atlantico (n=6), Bolivar (n=2),
      Cordoba (n=1), Magdalena (n=16), and Sucre (n=2)) were analyzed by real-time
      polymerase chain reaction (qPCR). Seventeen of the samples corresponded to soft
      cheese, five to semi-hard cheese and five to hard cheese.Results: In 62.9%
      (17/27) of the samples we detected Salmonella spp., in 70.4% (19/27), Listeria
      spp., and in 22.2% (6/27), Brucella spp., mainly from the department of
      Magdalena. In 62.5% (10/16) of the samples we detected Salmonella spp. and
      Listeria spp. while in the department of Atlantico, 50% (3/6) of the samples
      corresponded to Brucella spp.Conclusion: The results confirmed the presence of
      these microorganisms in all the samples of soft cheese from the Colombian
      Caribbean region.

PMID- 30184360
TI  - The drama of neglected tropical diseases

PMID- 30184361
TI  - Cutaneous leishmaniasis and pregnancy
AB  - We studied a 19-year-old woman, with a 4-month pregnancy who presented with four
      cutaneous leg ulcers of three months of evolution diagnosed by biopsy as
      cutaneous leishmaniasis. Direct smear and the leishmanin skin test were
      negative.Since all the usual medications for cutaneous leishmaniasis are
      contraindicated in pregnancy, she did not receive any treatment but cured
      spontaneously of her lesions during pregnancy. It is believed that cutaneous
      leishmaniasis does not carry danger for pregnant women and that there is no
      maternal-fetal transmission in humans, though it occurs in experimental
      animals.The patient gave birth without complications and both she and her son
      remained normal after two years of follow-up.

PMID- 30184362
TI  - Genetic variability in coding regions of the surface antigen and reverse
      transcriptase domain of hepatitis B virus polymerase, Colombia, 2002-2014
AB  - Introduction: Despite the availability of an effective vaccine and treatment to
      reduce the viral load and progressive hepatocellular injury, approximately 240
      million people worldwide are chronically infected with the hepatitis B virus
      (HBV). In Colombia, the circulation of different viral genotypes has been
      confirmed. Mutations in the genome have been associated to antiviral therapy
      resistance, viral escape to neutralizing antibodies, occult infection and
      progression to hepatocellular carcinoma.Objective: To identify the genotypes and
      the presence of mutations in the coding region of the surface (S) antigen and the
      reverse transcriptase (RT) domain of the polymerase of HBV obtained from serum
      samples for hepatitis B diagnosis received by the Instituto Nacional de Salud
      during the period 2002-2014.Materials and methods: A total of 495 serum samples
      with previous HBsAg reactive result were used for molecular detection. A fragment
      of 1,591 nucleotides was sequenced, and the corresponding phylogenetic analysis
      was performed.Results: We detected the viral genome of HBV in 66 samples and 28
      were successfully sequenced. The phylogenetic analysis allowed the identification
      of subgenotypes F3 and A2. The L180M and M204V resistance mutations were
      simultaneously identified in one sample, while the I169L resistance mutation was
      identified in another one. A single escape mutation, P120Q, was identified in one
      more. Two samples showed a deletion of 105 nucleotides in the preS1-preS2 region.
      Conclusions: The circulation of genotypes/subgenotypes F3 and A2 of HBV in
      Colombia was corroborated, as well as the presence of some resistance and escape
      mutations. The present study constitutes a contribution to the molecular
      epidemiology of HBV in Colombia.

PMID- 30184363
TI  - Molecular detection of pathogenic Leptospira in synanthropic and wild rodents
      captured in Yucatan, Mexico
AB  - Introduction: Leptospirosis is a zoonotic disease caused by bacteria of the genus
      Leptospira, which is endemic in Mexico and considered a public and veterinary
      health problem. Rodents are the most relevant reservoirs of Leptospira spp.
      because the bacteria establish and reproduce in its renal tissue and are excreted
      through the urine.Objective: To identify the presence of Leptospira spp. in renal
      tissue from rodents captured in Yucatan, Mexico.Materials and methods:
      Synanthropic and wild rodents were captured in the rural municipality of
      Cenotillo, Yucatan, Mexico. We collected one kidney from each rodent and
      extracted the total DNA. The identification of Leptospira spp. was done by
      detecting two fragments of the 16S rRNA gene using end-point polymerase chain
      reaction (PCR). We sequenced and analyzed positive products using alignment
      tools.Results: A total of 92 rodents belonging to seven different species were
      captured. The PCR yielded a global positivity of 5.4% (5/92). The alignment
      analysis of the sequenced products demonstrated a 100% of coverage and identity
      with Leptospira interrogans. This is the first molecular evidence of Leptospira
      spp. circulation in Heteromys gaumeri captured in Yucatan, Mexico.Conclusion: Our
      results evidenced that rodents of Yucatan are reservoirs of Leptospira spp. and
      participate in the infection cycle of leptospirosis in the region.

PMID- 30184364
TI  - [Current characteristics of tuberculosis and human immunodeficiency virus co
      infection in a cohort of hospitalized patients in Medellin, Colombia].
AB  - INTRODUCTION: Tuberculosis (TB) is an important cause of morbidity and mortality
      in HIV patients. It is unknown if the advent of molecular diagnostic methods and
      a greater availability of antiretroviral therapy (ART) in our country have
      changed some characteristics of the TB/HIV co-infection. OBJECTIVE: To describe
      the epidemiology, clinical features, diagnosis, resistance patterns, tuberculosis
      drug effects and mortality in co-infected patients. MATERIALS AND METHODS:
      Retrospective study based on the review of medical records of hospitalized co
      infected adults in a university hospital in Medellin, Colombia. RESULTS: A total
      of 178 patients was included in the study. TB and HIV diagnosis was simultaneous
      in 49.4%. In the moment of TB diagnosis, the median CD4 count was 61 cells/MUL
      (27-145). Pulmonary tuberculosis (PTB) occurred in 28% of patients,
      extrapulmonary (EPTB) in 23%, and mixed TB in 48.9%. The main EPTB affectations
      were lymphatic (55.4%), gastrointestinal (35.9%), and of the central nervous
      system (18.7%). Ziehl-Neelsen stain was positive in 137 patients (77%),
      mycobacterium culture in 121 (68%), and TB-PCR, in 85 of those patients in whom
      the test was done. Rifampicin resistance was detected in six cases (4.9%).
      Transaminases (ALT) increased in half of the patients during TB treatment, but
      only 10% met liver-toxicity criteria. In-hospital mortality was 11.3%. The single
      risk factor associated with mortality was CD4 count <50/MUL (RR=3.9; 95% CI: 1.36
      11.37; p=0.01). CONCLUSIONS: When it occurs as an opportunistic infection, TB
      usually leads to the diagnosis of advanced HIV disease. If used appropriately, TB
      diagnosis in these patients can be done by conventional methods. It is always
      necessary to monitor liver function during TB treatment and to rule out drug
      resistance.

PMID- 30184366
TI  - Exposure and sensitization to insects in allergic patients in the tropics
AB  - Introduction: Mites are an important source of allergens in the tropics. Other
      potential sources of allergens prevalent in the region such as insects have been
      poorly studied.Objective: To determine the relationship between exposure and
      allergic sensitization to cockroaches, mosquitos, ants and the interaction with
      mite sensitization.Materials and methods: We included patients with allergy tests
      for Blatella germanica, Aedes aegypti, Solenopsis invicta, Blomia tropicalis,
      Dermatophagoides farinae and D. pteronyssinus. IgE sensitization was evaluated by
      intraepidermal tests. Exposure to insects in houses was evaluated using traps for
      crawling and flying insects.Results: A total amount of 186 patients were
      included; 73 (39.2%) of them were sensitized to an insect (cockroaches: 21%,
      mosquitoes: 29%, ants: 26,3%), 71 (97.2%) also had sensitization to mites. Of the
      148 patients sensitized to mites, only 47.9% were sensitized to an insect. In
      total, 104 houses were evaluated: 74% had cockroaches, 22% ants, and 52%
      mosquitoes. Among insect-sensitized patients, the number of insects at home was
      directly related to the size of the weal generated during the skin test:
      Cockroaches, r=0.781, p<0.001; mosquitoes, r=0.811, p<0.001, and ants, r=0.840,
      p<0.001.Conclusion: Sensitization to insects is frequent in allergic populations
      of the tropics and is strongly associated with sensitization to mites.

PMID- 30184365
TI  - Tuberculosis and human immunodeficiency virus coinfection: Epidemiological
      situation in the department of Meta, 2010- 2015
AB  - Introduction. One third of the increase in tuberculosis cases is attributed to
      the spread of HIV.Objective. To describe the Tb/HIV coinfection in the department
      of Meta from 2010 to 2015.Materials and methods. We conducted an observational,
      descriptive and retrospective study. After selecting 219 cases for analysis, two
      new databases were constructed and analyzed in three phases: Identification of
      sociodemographic and clinical characteristics, indicators by municipality
      (prevalence and therapeutic success) and stratification in epidemiological
      scenarios according to the prevalence (burden) of the illness.Results. Sixty
      percent of the municipalities corresponded to scenario 2. People with Tb/HIV
      coinfection who had not been treated previously, had 2.39 times more probability
      of having therapeutic success compared to those previously treated, this
      association being statistically significant (RP=2,39; 95% CI 1,3-9,6;
      p=0,01).Conclusion. Stratification by epidemiological scenarios is useful for
      planning prevention and control activities.

PMID- 30184367
TI  - [First report of Dioctophyma renale (Nematoda, Dioctophymatidae) in Colombia].
AB  - Dioctophymosis is a zoonotic parasitic disease caused by Dioctophyma renale
      (Goeze, 1782). It is distributed worldwide and it affects a large number of wild
      and domestic mammals.Here we report the first confirmed case of canine
      dioctophymosis in Colombia. The animal was found dead in the streets of the
      municipality of Yondo, Antioquia, and its dead body was taken to the Instituto
      Universitario de la Paz (UNIPAZ) to carry out a necropsy.A parasite worm was
      found in the right kidney and sent for identification to the Laboratorio de
      Parasitologia of the Universidad de Santander (UDES). The specimen was identified
      as a male of D. renale upon observing the typical oval and transversely elongated
      bell-shaped bursa copulatrix with a spicule and no rays. Another important factor
      to confirm the diagnosis was the anatomical location in the kidney. This is the
      first time D. renale is reported in a stray dog in Colombia.

PMID- 30184368
TI  - [Nuclei ultrastructural changes of C6/36 cells infected with virus dengue type
      2].
AB  - INTRODUCTION: Dengue virus replication has been considered mainly cytoplasmic,
      however, studies indicate that some flaviviruses may use the intranuclear pathway
      as part of the machinery that the virus uses to increase infection capacity in
      the host cell. This paper describes alterations at nuclear level in the cell
      infected with dengue, which are likely involved in the virus replication
      processes. OBJECTIVE: This paper addresses the ultrastructural observations of
      C6/36 cells of the Aedes albopictus mosquito infected with dengue virus type 2.
      MATERIALS AND METHODS: C6/36 cells were infected in culture medium with the serum
      of a patient positively diagnosed for dengue 2. Subsequently, the cells were
      incubated for 10 days and the cytopathic effect was assessed. The cells were
      processed for immunofluorescence assays and transmission electron microscopy.
      RESULTS: The immunofluorescence assays confirmed the presence of viral protein E
      associated with cellular syncytia in the culture. In the ultrastructural study,
      the infected cells showed vesicular-tubular structures and dilated cisterns of
      the endoplasmic reticulum at the cytoplasmic level. Viral particles were found
      exclusively in cytoplasm localized within the vacuoles. Nuclei of cellular
      syncytia showed membrane structures arranged in a circular shape and, in some
      cases, these syncytia displayed lysis; in no case viral particles were observed
      at the nuclear level. CONCLUSIONS: The ultrastructural alterations of nuclei in
      cells infected with the dengue virus using electron microscopy techniques had not
      been reported before, as far as we know. It is likely that such modifications are
      associated with replicative processes at an intranuclear level as an alternate
      replication mechanism.

PMID- 30184369
TI  - Mycobacterioses identified in the National Reference Laboratory of Colombia from
      2012 to 2016
AB  - Introduction: In recent years, there has been an increase in the prevalence of
      mycobacterioses caused by non-tuberculous mycobacteria, which are considered as
      emerging pathogens. Their presence depends on several factors such as the
      clinical history, the health status of the affected person, and the presence of
      these microorganisms in the water, the soil, and the animals, among
      others.Objective: To describe the mycobacteria and the etiological agent
      identified in isolates received at the Laboratorio Nacional de Referencia de
      Micobacterias of the Instituto Nacional de Salud between 2012 and 2016.Materials
      and methods: We conducted a retrospective analysis of samples from 273 patients
      with mycobacterioses. We analyzed the following variables: mycobacteriosis type,
      etiological agent, and associated predisposing factors.Results: 57.1% of the
      cases presented pulmonary mycobacteriosis; 26%, cutaneous; 10.6%, disseminated,
      and 2.6%, lymphatic. We found the Mycobacterium avium complex more frequently in
      pulmonary mycobacteriosis, while M. abscessus was more frequent in the
      extrapulmonary types of the disease. Patients with pulmonary mycobacteriosis had
      a history of tuberculosis more frequently than those with extrapulmonary
      forms.Conclusion: These findings highlight the importance of the differential
      diagnosis between M. tuberculosis complex species and non-tuberculous
      mycobacteria since the latter are genetically resistant to conventional
      antituberculosis drugs.

PMID- 30184370
TI  - Novel larvicide tablets of Bacillus thuringiensis var. israelensis: Assessment of
      larvicidal effect on Aedes aegypti (Diptera: Culicidae) in Colombia.
AB  - INTRODUCTION: Aedes (Stegomyia) aegypti is the vector for dengue, chikungunya,
      and Zika arboviruses. Bti-CECIF is a bioinsecticide designed and developed in the
      form of a solid tablet for the control of this vector. It contains Bacillus
      thuringiensis var. israelensis (Bti) serotype H-14. OBJECTIVE: To evaluate under
      semi-field and field conditions the efficacy and residual activity of Bti-CECIF
      tablets on Aedes aegypti larvae in two Colombian municipalities. MATERIALS AND
      METHODS: We tested under semi-field conditions in plastic tanks (RotoplastTM)
      four different Bti doses (0.13, 0.40, 0.66 and 0.93 mg/L) in the municipality of
      Apartado, department of Antioquia, to assess Bti-CECIF efficacy (percentage of
      reduction of larval density) and the residual activity in water tanks containing
      A. aegypti third-instar larvae. The efficacy and residuality of the most lethal
      dose were subsequently evaluated under field conditions in cement tanks in the
      municipality of San Carlos, department of Cordoba. RESULTS: Under semi-field
      conditions, the highest tested dose exhibited the greatest residual activity (15
      days) after which larval mortality was 80%. Under field conditions, the highest
      tested Bti-CECIF doses showed 100% mortality and exhibited a residual activity of
      seven days in 90% of the tanks. CONCLUSION: Bti-CECIF tablets effectively
      controlled A. aegypti larvae under field conditions for up to seven days post
      treatment.

PMID- 30184371
TI  - Knowledge, practices and entomological aspects of dengue in Medellin, Colombia: A
      comparative study of neighborhoods with high and low incidence
AB  - Introduction: Dengue, mainly transmitted by Aedes aegypti, is a very important
      viral disease in terms of public health. Colombia is an endemoepidemic country
      for dengue and, in cities like Medellin, there are neighborhoods with high and
      low incidence. The disease dynamics in the neighborhoods might be determined by
      differences in the knowledge, practices and entomological aspects of the vector
      among the communities.Objective: To identify the knowledge and practices of
      residents of neighborhoods with high and low incidence of dengue, and to explore
      the entomological aspects related to the presence of the vector.Materials and
      methods: We conducted a cross-sectional study comparing two neighborhoods with
      high incidence and two with low incidence during the triennium of 2013-2015. A
      random sample of 100 houses per neighborhood was selected in order to evaluate
      the knowledge, practices and entomological aspects related to dengue. In
      addition, descriptive, bivariate and multivariate analyses (logistic regression)
      were performed.Results: In neighborhoods with high incidence, participants had
      not attended school or had only a primary school level of education (OR=1.69; 95%
      CI: 1.09-2.63). Additionally, they did not have health coverage or belonged to
      the subsidized regime (OR=2.16; 95% CI: 1.41-3.32). In contrast, they had a
      greater knowledge of the vector (OR=1.53; 95% CI: 1.00-2.35). In terms of
      practices, there was a greater chance of finding houses where water was stored
      (OR=1.69; 95% CI: 1.11-2.57) and regarding the entomological aspects, more houses
      with adult mosquitoes were found (OR=2.13 95% CI: 1.29-3.50).Conclusions: We
      found important differences among the neighborhoods regarding knowledge,
      practices, and the presence of adult stages of the vector, which helps to explain
      the epidemiology of dengue in these sites.

PMID- 30184372
TI  - Genetic diversity and population structure of Anopheles triannulatus s. l. in the
      department of Cordoba, Colombia, using DNA barcoding
AB  - Introduction: Anopheles triannulatus is not incriminated as a vector of malaria
      transmission in Colombia despite recent reports of infection with Plasmodium spp.
      in populations related to the northwestern and southeastern lineages. Genetic
      diversity can delimit information about gene flow and population differentiation
      in localities with malaria.Objective: To estimate the genetic diversity of An.
      triannulatus in five municipalities with high and low incidence of malaria in the
      department of Cordoba.Materials and methods: The entomological collections were
      done between August and November, 2016, in Tierralta, Puerto Libertador,
      Montelibano, Sahagun, and Planeta Rica. We used the COI barcoding fragment as
      molecular marker. The genetic analysis included the estimation of genetic
      parameters such as the diversity haplotype, the genetic structure, the gene flow,
      the Tajima's D test, the haplotype network, and the phylogenetic
      relationship.Results: We obtained 148 sequences with a length of 655 nucleotides
      of the COI gene, from which we derived 44 haplotypes. The H2 and H21 haplotypes
      were the most frequent in the populations. The values of the Tajima's D test were
      negative and not significant (p>0.10). The genetic structureindex (FST=0.01427)
      and the gene flow (Nm=17.27) evidenced no differentiation between sampled
      populations due to the high exchange of migrants. Using phylogenetic inferences
      and the haplotype network, we identified one single species without geographic
      differentiation or lineages in the geographic range studied.Conclusions: The
      genetic diversity calculated for An. triannulatus in this context indicated
      stable populations in constant exchange.

PMID- 30184373
TI  - Microcephaly in Colombia before the Zika outbreak: A systematic literature
      review.
AB  - INTRODUCTION: Microcephaly is characterized by a smaller than normal head
      circumference. Recently, Zika virus (ZV) has been associated with microcephaly.
      OBJECTIVE: To describe the prevalence of microcephaly in Colombia taking as the
      baseline the information from the period before the Zika virus infection
      epidemics. MATERIALS AND METHODS: We reviewed Medline, Scopus, Scielo, Lilacs and
      annual reports of congenital malformation monitoring systems across Latin
      America, among others sources, for articles published before April, 2015,
      reporting the prevalence of microcephaly in Colombia between 1982 and 2013.
      RESULTS: We identified 32 non-duplicate articles; we selected 25 articles for
      revision of which 12 met the criteria for inclusion in the systematic review,
      including 2,808,308 births. CONCLUSIONS: The prevalence of microcephaly in
      Colombia from 1982 to 2013, before the introduction of ZV, ranged from 0.3 to 3.1
      per 10,000 births, with an average of 1.8 (95% CI 1.7-1.8) per 10,000 births.
      These findings are important to determine if the prevalence after the
      introduction of the Zika virus infection registered significant changes.

PMID- 30184374
TI  - Severe disseminated acute toxoplasmosis in an adult immunocompetent patient from
      the Colombian Pacific
AB  - We present the case of a 72-year-old immunocompetent patient from Choco,
      Colombia, with a 12-day course of fever, headache, progressive neurological
      deterioration, and rapid evolution to multiorgan failure and death.In the
      histopathological study of tissues obtained at necropsy, tissue cysts
      morphologically suggestive of being bradyzoites of Toxoplasma gondii were
      identified and confirmed by immunohistochemistry in heart, brain, and striated
      muscle.

PMID- 30184376
TI  - Cutaneous leishmaniasis and pregnancy

PMID- 30184375
TI  - In vitro culture of L3 larvae of nematodes obtained from the African giant snail
      Lissachatina fulica (Mollusca: Gastropoda) in Santa Fe de Antioquia.
AB  - INTRODUCTION: Over 170 municipalities in Colombia have been invaded by
      Lissachatina fulica, an African snail that can carry larvae of nematodes of
      interest in human and veterinary health. Nematodes enter the host snail as larvae
      L1 and then change to L2 and L3, the infectious form for vertebrates. OBJECTIVE:
      To standardize culture in vitro of L3 carried by L. fulica from Santa Fe de
      Antioquia. MATERIALS AND METHODS: Between July and November, 2014, 10 snails were
      collected, killed, and conserved with HCl 0.7%. Larvae were recovered using the
      Baermann technique and cultured for 36 days in Schneider, DMEM and RPMI media,
      with and without SFB 20% and distilled water with SFB 20%. Replacements were made
      every 36 hours; larvae were measured with an ocular micrometer on a microscope.
      Summary statistics were estimated; box and whisker plots were made; the t Student
      test was performed in SPSS 18TM. A p-value below 0.05 was assumed as significant.
      RESULTS: Fifty per cent of the larvae survived. The highest survival and growth
      was 85% in supplemented DMEM. The final average length of larvae in supplemented
      media exceeded the initial one. There were significant differences between the
      average length of larvae cultured in supplemented media and the initial length.
      The initial width of larvae did not change. CONCLUSIONS: The best medium for the
      culture of L3 larvae was supplemented DMEM. The length provided more information
      than the width for the larval growth evaluation. The larvae studied did not
      correspond to Angiostrongylus cantonensis, A. costaricensis or Aelurostrongylus
      abstrusus.

PMID- 30184377
TI  - Colombian Dental Literature During the Twentieth Century.
AB  - Colombia is one of the Latin American countries in which both research and
      academic writing are considered virgin areas. The dental profession is not the
      exception. The purpose of this paper is to construct a database of the dental
      books written in Colombia from the mid-1800s to 1900s and to analyze those books
      according to the decades in which they were published. The first book published
      in Colombia on Dentistry was Odontotecnia u observaciones sobre la estructura,
      fisiologia, anatomia y enfermedades de los dientes (Dental Techniques or
      Observations on the Structure, Physiology, Anatomy and Dental Diseases), written
      by American dentist Joseph Watson ver Valen and released in Bogota in 1849. In
      150 years, a total of 72 dental books were found, most of which were published in
      Bogota and Medellin.

PMID- 30184378
TI  - Dental Trade Cards XLVI.

PMID- 30184379
TI  - Esthetics, Cosmetics, Prosthetics: Is This What Dentistry is About?

PMID- 30184380
TI  - The Past, Present, and Future of Dentoalveolar Surgery in China.
AB  - Dentoalveolar surgery, formerly known as dental surgery or oral surgery, is one
      of the basic branches of oral and maxillofacial surgery. While it has a long
      history; however, there are great differences in its evolution globally. This
      article presents a brief review on the development of dentoalveolar surgery
      internationally. Furthermore, a systematic review on its development in China, is
      detailed in 6 stages. However, while its development in China since 2005 has been
      most profound, improvements are still needed in treatment concepts, instruments,
      treatment processes, attention to high-risk populations and cooperation with
      other dental/medical disciplines. Future projections based on present standards
      of care are also presented.

PMID- 30184381
TI  - Historical Perspectives on the Evolution and Development of Organizations
      Committed to Excellence in Dental Education.
AB  - Today's organization that is committed solely to excellence in dental education,
      the ADEA (American Dental Educators Association) evolved from a wide variety of
      sources in the past 140 years. Exploration of that evolution has identified a
      wide range of organizations and philosophies, all of which have contributed
      immensely to the present-day structure of the ADEA.

PMID- 30184382
TI  - From the Archives: Vol. 6, Nos. 7 & 8.

PMID- 30184383
TI  - "Karius and Baktus": A Critical Appraisal of Enger's Seminal Storybook.
AB  - Karius and Baktus, first published in 1949, is one of the most influential
      storybooks with dental caries as main theme and it remains in wide use for
      domestic health education. This study aimed at assessing oral health related
      contents of the historic storybook in the light of the current body of cariologic
      evidence. Two investigators independently identified phrases in the storybook
      with cariologically relevant content. Dental health related contents were
      systematically evaluated with respect to the current body of cariologic evidence.
      Karius and Baktus highlights important etiopathogenetic and preventive aspects
      such as sugars consumption and tooth brushing with toothpaste. Its behavior
      management techniques and narrative health didactics concerning dental care for
      children are, however, outmoded. The cariologic core statements in Karius and
      Baktus have remained valid whereas certain narrative features may have some
      drawbacks when employing the historic storybook for educational purposes for
      young children.

PMID- 30184384
TI  - Put a Frog in Your Mouth: Toothache 'Cures' from Nineteenth- and Twentieth
      Century Ireland.
AB  - During the late nineteenth and early twentieth centuries, toothache must have
      been a common complaint in Ireland, to judge from the number of toothache 'cures'
      reported as part of The Schools' Collection (SC) or 'Bailiuchan na Scol', a
      folklore-collecting scheme that was undertaken in the Irish Republic in 1937 and
      1938, and upon which this article is based. These cures range from quasi-medical
      treatments, such as packing the affected tooth with tobacco, to more folkloric,
      or magico-religious cures, such as licking a frog or pulling out a tooth from a
      corpse, as well as herbal and mineral remedies.

PMID- 30184386
TI  - Literature in Review "The Golden Age of Orthodontics, Decline, and Aftermath: A
      History of the Business of Orthodontics".

PMID- 30184385
TI  - Charles Darwin and the Dentists.
AB  - Charles Darwin suffered relapsing, debilitating illness for most of his adult
      life with many symptoms. His most prominent complaints were episodic nausea,
      retching and vomiting. As is common in patients with repeated vomiting he
      developed dental problems, problems that may be dated back to his voyage on the
      Beagle and his vomiting due to persistent seasickness. Dental problems continued
      after the voyage and he was one of the first patients to have extractions under
      chloroform. Watching a dental procedure caused Darwin great distress, much as
      surgical and obstetric procedures had previously caused him distress with onset
      of symptoms. Darwin's dental experiences are consistent with the proposed
      diagnosis of his lifetime illness- patients with similar illnesses today have
      much the same dental problems. Dentists also helped Darwin with his researches
      and collection of specimens. In Darwin's day, dentists, like country clergymen,
      had time to follow other interests. Dentists contributed to Darwin's dental
      health, to the dental health of his family and to Darwin's work and biological
      studies. Dentists, in their own right, were also prominent in developing our
      biological understanding.

PMID- 30184387
TI  - The Dentaphone: Hearing Through the Teeth.

PMID- 30184388
TI  - From the Archives: Vol. 6, Nos. 9 & 10.

PMID- 30184389
TI  - [The Actuality of Inter-Sectoral Interaction in Development of Mechanisms of
      Healthy Aging].
AB  - Nowadays, issues of healthy aging are actual for all EU countries. The increasing
      of percentage of population of elderly age during last decade issues a challenge
      to national governments in various economic sectors concerning development of
      mechanisms favoring decreasing of economic burden of diseases, social and
      psychological problems of aging population and supporting health preservation in
      elderly age.

PMID- 30184390
TI  - [The Tendencies of Prevalence of Diseases of Musculoskeletal System and
      Connective Tissue in Moscow Adult Population].
AB  - The article presents the results of analysis of trends in morbidity and
      dispensary observation of Moscow adult population with diseases of
      musculoskeletal system and connective tissue. The analysis was applied to data
      from statistical report forms # 12 of the Moscow Health Care Department in 2012
      2016. The stability of percentage of diseases of musculoskeletal system in the
      structure of total and primary morbidity during last 5 years was established. The
      significant dynamics of indices of total morbidity is absent. The statistically
      significant descending trend if primary morbidity at the expense of deforming
      dorsopathies in the age group older than 55 years was established. The deforming
      dorsopathies hold first place in the structure of diseases of musculoskeletal
      system. The dynamics of decreasing of indices of total morbidity of the given
      pathology in the age group of 18-55 years and older than 55 years is
      statistically non-significant. The statistically significant ascending tendency
      of indices of total morbidity of arthroses of adult population and primary
      morbidity of synovial membranes and tendons in the age group of 18-55 years is
      established. The established in adult population and individuals aged 18-55 years
      both decreasing of number of being dispensary registered on the subject of
      pathology of musculoskeletal system and its increasing among individuals older
      than 55 years are statistically non-significant. The trend of dropping of
      indicator of being on dispensary registration of individuals with primarily
      diagnosed pathology is also insignificant. The correlation between rate of
      dispensary registration and primary morbidity, including particular pathologies,
      is absent.

PMID- 30184391
TI  - [The Analysis of Social Economic Factors Impact on Epidemic Situation with
      Tuberculosis in Regions of the Russian Federation].
AB  - The article presents original multi-factorial linear regression models developed
      on the basis of panel structure of data. The distribution of the regions of the
      Russian Federation according tuberculosis burden was implemented using cluster
      analysis technique. The evaluation of degree of impact of analyzed factors to
      epidemic process was implemented using Pratt metric. In overall, approximately
      100,000 records from 78 regions of the Russian Federation were processed. four
      regional clusters were marked out differentiating by level of morbidity,
      prevalence and mortality of tuberculosis. The diversity of social economic
      factors impacting the main indices of epidemic process is reducing as its
      intensity increases. If in the first cluster 7 factors impacted on morbidity and
      4 factors -- on mortality, then in the fourth cluster only 1 factor impacted
      morbidity and 2 -- on mortality. At that, intensity of their impact on epidemic
      process increased significantly. So, for example, the role of such factor as
      "Area of housing per capita" in decreasing of tuberculosis morbidity among
      regions of the 4th cluster assessed in 79%, and among regions of 1st cluster only
      in 17%. The study results demonstrated that modern techniques of machine learning
      permit to develop models for quantification assessing of impact of social
      economic conditions of a particular region on activity of epidemic process of
      tuberculosis.

PMID- 30184392
TI  - [The Organization of Specialized Medical Care Support to Victims of Road Traffic
      Accidents Using the Informational System for Issuing Passports of Traumatological
      Centers of The Moscow Oblast].
AB  - Within the framework of the Moscow Oblast Integrated Medical Informational
      Analytical System an informational system of issuing passports of traumatological
      centers was developed. This system permits to implement statistical and economic
      analysis with the purpose of applying financial modeling of functioning of
      traumatological centers for the benefit of supporting high quality treatment,
      prevention of economic losses and decreasing of lethality after road accidents in
      medical organizations.

PMID- 30184393
TI  - [The Post-Operative Complications as an Evaluation Indicator of Efficiency of
      Functioning of Three-Level System of Medical Care Support According to Urology
      Profile in the Voronezh Oblast].
AB  - In the Voronezh Oblast, the modernization of system of medical care support of
      patients with urological pathology was implemented with the purpose of increasing
      efficiency of the urological service functioning. This action affected all
      levels: early active detection of urological pathology, standardization of
      examination and treatment, routing of patients, strict control by way of monthly
      reports of medical institutions of the Oblast at the level of hospital and out
      patient services, supervisory visits of specialists to districts and efficient
      control on part of the Oblast Chief Out-of-Staff Urologist. In the course of
      study it is established that key indices characterizing efficiency of functioning
      of the regional system of urological care of population are admitted the levels
      of unreasonably prolonged conservative treatment and also reasonably application
      of low invasive and high-tech intervention, implementation of standardization of
      the curative diagnostic process, rate of post-operative complications, level of
      economic costs of diagnostic and treatment, level of medical competence of
      personnel and degree of early detection of urological pathology that is validated
      by statistically reliable positive effect at the expense of their adjustment. The
      detection of advanced forms of diseases results in increased disability,
      increased economic costs per each patient in need of several operative
      interventions and highly qualified care. The number of post-operative
      complications is considered as an indicator of timeliness and adequacy of
      provided medical care to patients. The article presents an analysis of efficiency
      of the three-level system of medical care support according indicator of post
      operative complications.

PMID- 30184394
TI  - [The Traumatogenic Factors of Life-Style of Rural Population].
AB  - The article substantiates actuality of problem, presents study methodology and
      classification of leading traumatogenic factors of life-style of rural
      population. The results of medical social monitoring were used as a basis for
      ranking degree of evidence of traumatogenic factors impacting on population
      health in rural district. The study established a high level of prevalence of
      traumatogenic factors in population of rural district. The following groups were
      marked out according degree of traumatogenicity: very high impact, high impact,
      average impact, low impact, very low impact and no impact established. In adult
      population of rural district, a high prevalence of industrial traumatic factors
      was established as well as traumatogenic agricultural labor, significant
      distancing of place of residence from work place, community uncomfortableness,
      bad highways, polluted basins, availability of ramshackle household buildings,
      availability of domestic and agricultural animals, motor transport means, high
      rate of alcohol consumption. The differences are established between prevalence
      of traumatogenic factors in various settlements of rural district. As far as
      distancing from district center increases in direction of rural settlements
      decreasing of quality of accomplishment of roads is noted as well as community
      uncomfortableness of accommodation at the expense of increasing of private
      sector, increasing of number of owners of lawn-and-garden and homestead lands
      with extremely low level of material welfare, increasing of individuals consuming
      alcohol beverage. The following principles of system of monitoring og
      traumatogenic factors are substantiated: complex character, intersectoral
      integration, maintenance of strict ethic rues, feedback.

PMID- 30184395
TI  - [On the Results of Analysis of Quality of Life of Paramedical Personnel].
AB  - The quality of life of paramedical personnel is an important and little-studied
      characteristic of health that directly conditions quality of medical care
      support. The survey of 400 paramedical workers using questionnaire SF-36
      demonstrated that an average grade of quality of life made up to 68.1+/-1.2. This
      grade decreases as increases age of workers. It is minimal in case of employment
      service 11-15 years and it is lower in medical nurses as compared with
      administrators of nursing services. The similar tendency is noted in workers of
      out-patient network as compared with workers of hospitals. Among all the
      components of quality of life a minimal grade is specific to level of social
      functioning and maximal grade -- to level of physical functioning. The analysis
      of level of quality of life of workers with different conditions of their life
      activity demonstrated that the most differences were specific to such factors as
      chronic diseases, level of income, character of personnel relationships,
      availability of organizational problems at work, prestige of medical nurse
      profession. The study substantiated importance of factors of non-material
      motivation of labor of paramedical personnel that can promote increasing of their
      quality of life and stimulate more effective work: amelioration of organizational
      conditions, target activity in development of optimal psychological climate in
      personnel staff, increasing of level of organizational, including deontological
      culture of all workers, increasing of prestige of profession of paramedical
      personnel, necessity of further development of system of labor remuneration.

PMID- 30184396
TI  - [The Medical Social Efficiency of Joint Confinement of Mother and Child in Place
      of Imprisonment].
AB  - The article, on the basis of the results of study of 2016, analyzes a comparative
      medical social effect of conjoint and separate residing of mother and child in
      the Children's Homes of the Penal Enforcement System. The materials of study
      consisted of original observations while working in the given system, data of
      reports of the Federal Penitentiary Service of Russia concerning medical care of
      women and children in 2011-2015 and data of address requests to the Children's
      homes under correctional facility in 2013 and 2015. The experience of functioning
      of the Children's homes of penitentiary system is summarized. The positive effect
      of conjoint keeping to indices of coverage with breast feeding is established.
      The coverage of natural and mixed feeding amounted to 65% in Children's Homes,
      including 83% in Children's Homes with conjoint residing of mother and child in
      Children's Homes and in other Children's Homes -- 43% (p<0.05). In 2015, a single
      refusal of child by condemned mother occurred in Children's Homes, while in 2013
      there were 4 of such refusals (p<0.05). In Children homes with extended
      department of conjoint residence primary morbidity of children made up to
      1,6790/00 and in comparison, group -- 20140/00 that is reliably higher (p<0.05).
      According data of primary morbidity occurred decreasing of pool of diseases of
      respiratory organs from 1,002 to 872 per 1,000 children due to brining into
      operation of dormitory of conjoint residence of mother and child. This occurrence
      resulted in decreasing per 12% of number of hospitalizations by emergency
      indications. The conjoint residence of condemned mother and newborn results in
      harmonious growth, physical, neuropsychic development of child and also in
      development of motherhood feelings that is an important factor of re
      socialization of the condemned woman. It is proposed to introduce normatively
      obligatory conjoint residence of mother and child in Children's homes of the
      Penal Enforcement System.

PMID- 30184397
TI  - [The Prevalence of Sexually Transmitted Infections Depending on Social Belonging
      of Population].
AB  - The sexually transmitted infections represent an actual medical social problem.
      The purpose of study is to analyze characteristics of their prevalence in various
      social groups of population. The data from annual reports on morbidity in the
      Republic of Udmurtia in 2006-2015 is analyzed. The analysis of morbidity of
      sexually transmitted infections during the mentioned period demonstrated the
      highest morbidity of chlamydia infection (from 135 in 2006 to 194,8 in 2015 per
      100 000 of population) and trichomoniasis (from 63.5 in 2006 to 183.4 in 2015 per
      100 000 of population). In the structure of morbidity in 2006 trichomoniasis went
      to 25.6+/-1.2%, chlamydia infection -- 19+/-0.9%, syphilis -- 17.6+/-0.8%. In the
      end of analyzed period, chlamydia infection was in the lead in overall structure
      of morbidity. The analysis of morbidity subject to social belonging demonstrated
      that in relation to syphilis and trichomoniasis preponderance the diseased was in
      the direction of non-working population while in case of other infections in the
      direction of workers of middle and minor business. The results of study
      demonstrated the necessity of development of activities in area of primary
      prevention among working population, workers of middle and minor business and
      student youth.

PMID- 30184398
TI  - [The Modern Characteristics of Anti-Tuberculosis Care Support of Population of
      the Chechen Republic].
AB  - Despite a steady tendency of decreasing of indices of morbidity of tuberculosis
      of population of the Chechen Republic, the problems related to early diagnosis of
      tuberculosis and organization of specialized medical care of patients continue to
      be unresolved. The questionnaire survey of administrators of anti-tuberculosis
      medical organizations of the Chechen Republic was carried out with the purpose of
      establishing difficulties in medical care support of patients with tuberculosis
      and determining main directions of their overcoming. The results of study
      demonstrated that main problems are asocial behavior of patients, inadequate
      staffing of institutions with medical and paramedical personnel, absence of
      proper relationship with other medical organizations, inadequate level of
      financing. The administrators indicated as main directions of solving problems
      increasing of remuneration of labor of medical personnel of anti-tuberculosis
      medical organizations, development of social defense of patients, physicians and
      population, alteration of actual normative legal base according to modern social
      economic conditions, enhancement of preventive direction of work, optimization of
      manning table and standards of work load of physicians and also development of
      tactics of treatment and re-organization of dispensary observation of patients
      with tuberculosis.

PMID- 30184399
TI  - [The Medical Sociological Monitoring as a Strategic Element of Management of
      Medical Care Quality].
AB  - The sociological survey of physicians and patients was carried out in the state
      and private sector of medical care services with the purpose of comparison of
      various defects of paper work and quality of provided medical services. The
      material of study consisted of the results of survey in state and private medical
      institutions of Moscow. The quality of medical paper work, satisfaction of
      patients with received discharge epicrisis, quality of paper work for expertise
      of medical commission, rate of detection of defects and breaches in medical paper
      work were evaluated. The study object included patients aged 18-94 years received
      hospital care in 2016-2017 and provided voluntary informed consent to
      participation in survey. The study results demonstrated that in state and private
      medical institutions patients in overall were satisfied both with quality of
      proposed services and informativeness of discharge epicrisis at discharge from
      hospital. A number of established defects in execution of discharge epicrisis
      negatively affect overall perception of applied treatment and force to apply
      additional efforts to visit medical institution iteratively with the purpose of
      elimination of defects of lexical character and lacking in documentation the
      results of implemented clinical instrumental analyses and consultations of
      adjacent specialists.

PMID- 30184400
TI  - [The Organization of Stomatological Care to Patients with Various Somatic
      Pathology].
AB  - The article considers actual national and international publications concerning
      problems of organization and characteristics of stomatological care support of
      patients with particular types of somatic pathology. The new approaches are
      analyzed concerning organization of efficient stomatological care of patients
      with various diseases.

PMID- 30184401
TI  - [Why Is It So Important to Invest into Breast-Feeding and How to Ameliorate Its
      Practice?]
AB  - Nowadays, the breast-feeding, despite the approved advantages, is not a standard
      in many communities. The multi-factorial determinants determining its prevalence
      need to be supported at various levels - from legal and legislative one to views
      and values of society, conditions of women's labor and also health care system
      that can develop a favorable environment for breast-feeding. The breast-feeding
      effects positively on health, economic development and ecology and therefor it is
      a benefit for children, women and whole society in short-term and long-term
      perspective. The defense, propaganda and support of breast-feeding need a
      political will, and financial investments to implement its advantages.

PMID- 30184402
TI  - [The Priority Directions of Children Health Support in Conditions of the Region
      During the Great Patriotic War].
AB  - The article presents analysis of state of children health care in Kabardino
      Balkaria during the Great Patriotic War (1941-1945). The significant hardships
      are demonstrated concerning children health support during German occupation in
      winter 1942-1943 and during post-occupation period. The significant increase of
      morbidity children infections, especially measles, undernourishment, hard
      domestic conditions were specific for this period. The main causes of high
      mortality among children were pneumonia, acute diseases of gastro-intestinal
      tract, whooping cough, scarlatina, diphtheria. The acute deficiency of medical
      personnel and untimely implementation of planned inoculations resulted
      indecreasing of the level of preventive activities among children population. The
      number of children consultations shortened twice. The special significance for
      development of pediatric service played organization of municipal and district
      pediatricians, preventive appointments of healthy children and home-nursing
      activities at the pediatric districts. The development of children health care
      characterized by increasing of load on medical institutions, implementation of
      emergency activities under guidance of departments organized by the Narkomzdrav
      of the Republic. A significant portion of activities was implemented by public
      organizations. The foundations of support of children evacuated ti the Republic
      and foundations of support of orphan children were organized.

PMID- 30184403
TI  - The application of Urban Health Equity Assessment and Response Tool to assess
      health inequity among dwellers of an urban slum area in Giza Governorate, Egypt.
AB  - BACKGROUND: The WHO in 2008 developed the Urban Health Equity Assessment and
      Response Tool. It is a user-friendly guide for stakeholders and decision makers
      at national and local levels to identify health inequities. Moreover, using such
      tool will facilitate decisions on viable and effective strategies, interventions,
      and actions that should be used to reduce health inequities. AIM: To assess the
      health equity in a disadvantaged district (Gezerit El Warak) located in Giza
      province, Egypt. MATERIALS AND METHODS: A population-based survey was conducted
      in the study district. A total of 643 heads of households were interviewed using
      Urban Health Equity Assessment and Response developed by WHO. Indicators of key
      health outcomes and major social determinants were calculated and then compared
      with the corresponding national indicators. RESULTS: The results of social
      determinants of health showed lower performance than national figures in the core
      indicators illiteracy (42.5%) and male tobacco smoking (56.0%), whereas good
      performance was reported for unemployment among adults (2.0%), fully immunized
      infants (95.1%), and females' overweight (34.5%)/obesity (38.0%). The main
      problem encountered was the inadequate physical infrastructure, mainly safe
      drinking water and sewage disposal system. The health outcome indicators revealed
      higher prevalence of hypertension among both males (20.7%) and females (19.2%).
      History of diabetes mellitus was markedly higher than the national figures among
      both males (11.5%) or females (9.6%). CONCLUSION: Compared with the national
      indicators, the main health determinants with low performance encountered in the
      study area included the physical infrastructure and high prevalence of male
      tobacco smoking. Health outcome indicators with low performance were diabetes and
      hypertension. The response of stakeholders was positive and immediate actions
      were taken to tackle some of the low-performance indicators.

PMID- 30184404
TI  - Immunogenicity of compulsory and booster doses of hepatitis B vaccine among
      children in Cairo, Egypt.
AB  - BACKGROUND: Although Egypt had adopted implementation of routine infant hepatitis
      B virus (HBV) vaccination in 1992, its effectiveness is not evaluated on a
      national scale. Assessment of early and long-term seroprotection after compulsory
      vaccination is an important measure for monitoring the success of the vaccination
      program. AIM: The aim of this study was to assess HBV seroprotection and immune
      memory in children and adolescents who were vaccinated during infancy in Cairo
      Governorate. MATERIALS AND METHODS: The study was carried out in two phases. The
      first phase was a cross-sectional study carried out in five districts in Cairo
      Governorate, recruiting 819 children in the age range of 9 months to 16 years.
      All children had received full doses of the compulsory HBV vaccination. Serum
      samples were taken from each child and assessed for antibody against hepatitis B
      virus surface antigen (anti-HBs) titer; total antibodies against HBV core
      antigen, and HBV surface antigen. HBV DNA was investigated by real-time PCR for
      those who were HBV core antigen or HBV surface antigen positive. In the second
      phase, nonseroprotected children (anti-HBs <10 IU/I) received HBV booster dose.
      AntiHBs titer was reassessed after 4 weeks to identify anamnestic response.
      Individuals showing antibody concentrations ofless than 10 IU/l were then given
      an additional complete course of vaccination. RESULTS: Four out of 819 children
      had HBV breakthrough infection. The seroprotection rate was 60.7%, and was
      significantly higher among children aged less than 5 years compared to the older
      age groups and among boys compared to girls. Multivariate logistic analysis
      showed age as the only independent predictor of low anti-HBs titer. About 95% of
      nonseroprotected children developed anamnestic response postbooster. Anti-HBs
      geometric mean titer (GMT) increased significantly from pre-booster (13.8+/
      16.9IU/L) compared to post-booster (307+/-6.0IU/L, P<0.001). Anti-HBs GMT was
      significantly higher among children with prebooster anti-HBs level >=1 IU/l
      (424.9+/-4.4 IU/l) compared to children with undetectable level (178.3+/-8.3).
      CONCLUSION: Despite waning of anti-HBs over time, long-term protection still
      exists. The high anamnestic response rate signifies the existence of immune
      memory and giving a booster dose is not recommended. However, we suggest that
      prolonged follow up and surveillance of vaccinees immunized at an early age
      should be continued.

PMID- 30184405
TI  - Internet addiction among medical students of Sohag University, Egypt.
AB  - BACKGROUND: Internet use may have many drawbacks. Among the main threats caused
      by internet use is wasting time and lack of self-control over internet use, which
      amounts to the level of addiction with several deleterious consequences. AIM: The
      aim of the study is to identify the prevalence of internet addiction (IA) and
      associated factors among medical students in Sohag University, Egypt. MATERIALS
      AND METHODS: The cross-sectional survey was conducted in October 2016 and
      November 2016 on a random sample of 587 students selected from three medical
      faculties in Sohag University. The self-administered questionnaire consisted of
      two sections; the first section was concerned with collecting the
      sociodemographic data, data about student's relations and internet use
      characteristics; the second one aimed at assessment of the level of IA using
      Young's 20-item scale for IA. RESULTS: The findings show that the prevalence of
      IA was 47.7%. Male sex, internet access on mobile phones, easy internet access at
      home, using internet for browsing social media and e-mail, and bad relation with
      the family were the most important predictors of IA. CONCLUSION: The high
      prevalence of IA among medical students in Sohag University (47.7%) is a matter
      of concern. Identification of factors significantly associated with IA can help
      in the planning of comprehensive programs to raise public awareness about the
      hazards and determinants of IA targeting the high-risk groups.

PMID- 30184406
TI  - Effectiveness of antismoking drug treatment in patients with psychiatric
      comorbidity compared with patients without this comorbidity.
AB  - BACKGROUND: There is a relationship between smoking and some psychiatric
      disorders, and there is doubt whether antismoking treatment will be more complex
      because of psychiatric disorder. AIM: To analyze the differences in treatment
      success rates among patients without psychiatric disorder and patients with
      psychiatric disorder who have received complete pharmacological treatment.
      MATERIALS AND METHODS: A retrospective cohort study was conducted using the
      records of patients completely treated at Albacete University Hospital Complex
      during 2011. The sample comprised 293 patients seen in 2011. We treated only 73
      patients and divided them into patients with or without psychiatric disorders. We
      analyzed the following variables: sex, age, age at smoking onset, previous
      quitting attempts, cigarettes per day, CO-oximetry, Fagerstrom test, Richmond
      test, alcoholism, treatment distribution, treatment failure, success, and
      relapse. RESULTS: Of a total sample of 293 patients seen in 2011, 73 patients
      were treated: 43 were men and 30 were women. Overall, 37% had psychiatric
      disorder (five men and 22 women). Treatment was successful in 51 (70%) patients.
      There were no differences between the demographic characteristics of the two
      groups, except for sex (P<0.05); or regarding success, failure, or relapse; or
      regarding success analyzed separately according to sex distribution. CONCLUSION:
      Smoking cessation treatment is equally effective in patients with and without
      psychiatric disorders. The characteristics of the patients with psychiatric
      disorders who completed the pharmacological treatment did not differ in
      intensity, motivation, or dependence from those with no psychiatric comorbidity.
      Smoking women have more psychiatric morbidity; however, the treatment is
      effective.

PMID- 30184407
TI  - Effect of physicians' smoking status on their knowledge, attitude, opinions and
      practices of smoking cessation in a University Hospital, in Egypt.
AB  - BACKGROUND: The tobacco epidemic is one of the biggest public health threats.
      Smoking prevalence and smoking cessation intentions among physicians vary from a
      country/community to another. Recently, a global reduction in the rates of
      smoking among healthcare providers is observed. AIM: This study aims to describe
      the effect of physicians' smoking status on their knowledge, attitude, opinions,
      and practices of smoking cessation in patients in a Tertiary Healthcare
      University Hospital in Cairo, Egypt. MATERIALS AND METHODS: A cross-sectional
      study was carried out at four specialized hospitals in a Tertiary Healthcare
      University Hospital in Cairo. Anonymous questionnaires included sociodemographic,
      occupational data, history of smoking, smoking-related knowledge, attitude, and
      practices of smoking cessation counselling. RESULTS: The study included 521
      physicians, 26.5% of physicians have never received training on smoking-cessation
      approaches. The prevalence of current smoking among the studied physicians was
      21.5%. Only 45.5% of smoking physicians have never smoked in front of a patient
      and 27.7% have no compliance to the smoke-free policy in nonsmoking areas.
      Smoking physicians were significantly less likely than nonsmokers to identify the
      effect of passive smoking on the heart, lungs, and on neonates (67.9, 58.9, and
      53.6% compared with 83.6, 77, 60, and 56.7%, respectively). A lower percentage of
      smoking physicians (34.8%) agreed that smoking physicians are less likely to
      convince patients to quit smoking compared with about 60% of nonsmoking
      physicians. The practices related to smoking cessation as reported by both
      smokers and nonsmokers were inadequate. CONCLUSION: Smoking status significantly
      affects the knowledge, attitude, and some practices of physicians related to
      smoking cessation counselling. Training on smoking cessation should be enforced
      during undergraduate and postgraduate studies of physicians.

PMID- 30184409
TI  - Consumer-oriented evaluation of the service provided by the department of health
      education and information in Alexandria, Egypt.
AB  - BACKGROUND: Assessing consumers' satisfaction with health education services can
      help in monitoring the quality of provided service and understanding consumers'
      perceptions and utilization patterns of the service. MATERIALS AND METHODS: A
      cross-sectional descriptive study targeting consumers attending the health
      education sessions provided by Alexandria Department of Health Education and
      Information (DHEI) at different governmental health facilities and
      nongovernmental organizations was performed. A simple random sample of 400
      participants was interviewed using an interview questionnaire assessing
      respondents' socioeconomic characteristics, health literacy, attitude toward
      health education services, and satisfaction with the health education service
      provided by the DHEI. RESULTS: Approximately 70% of the consumers' sample showed
      fair health literacy level. Most of the sample mentioned physicians a credible
      source of health knowledge followed by 58.8% who selected health education
      sessions as another trusted health information source. Overall, 90% of the sample
      was highly satisfied by the service overall. Behavior and skills of the service
      providers were the most satisfying aspects, whereas health education materials
      obtained the least satisfaction. Consumers' educational level and healthcare
      affordability proved to have a significant positive influence on their
      satisfaction (beta=0.307 and 0.191, respectively) whereas occupation and family
      income showed a significant negative influence (P<0.001). CONCLUSION: The service
      provided by Alexandria DHEI is highly satisfying to its target audience mainly in
      terms of providers and accessibility. Enhancing the technical skills of the
      department staff through training is highly recommended. The department is also
      recommended to advocate for the credibility of social workers and health visitors
      as health educators among the community.

PMID- 30184408
TI  - Pattern and correlates of cyberbullying victimization among Egyptian university
      students in Beni-Suef, Egypt
AB  - BACKGROUND: The expansion of the online environment has unveiled many cyber risks
      and potentials for abuse such as cyberbullying. Cyberbullying carries many
      negative psychological impacts that affect mainly young people. AIM: The
      objective of our study is to explore the of cyberbullying victimization among
      Egyptian university students in Beni-Suef and investigate factors correlating
      with it. MATERIALS AND METHODS: In this cross-sectional study, a multi-stage
      random sampling was used to include a total of 6740 students from all grade
      levels in all faculties (n=28) of Beni-Suef University. After 4 focus group
      discussions, a self-administered questionnaire was designed for data collection.
      The questionnaire comprised three sections including questions about selected
      socio-demographic characteristics, exposure to cyberbullying in the past 6
      months, and factors associated with victimization. RESULTS: Almost half of our
      students (48.2%) reported experiencing cyberbullying victimization in the past 6
      months. Female students, students living in urban areas and those who spent more
      hours using the internet reported more exposure (p<0.001). Harassment was the
      main type stated by females (79.8%) while flaming was excessively reported by
      males (51.8%). Students responded mostly by anger (63.1%), hatred (23.2%) and
      sorrow (22.6%) towards the worst victimization incidents. CONCLUSION:
      Cyberbullying victimization is highly prevalent amongst university students in
      Beni-Suef and female students are more vulnerable to exposure, Implementing anti
      cyberbullying programs tailored for university students will be a major step.
      Such programs should include anti-cyberbullying policies and materials, and
      provision of guidance for students, their parents and their teaching staff.

PMID- 30184411
TI  - Wounding activates a 47 kDa MAP kinase in Catharanthus roseus (L.) G. Don.
AB  - Catharanthus roseus (L.) G. Don. is an important medicinal plant (Fam.
      Apocynaceae) known for its alkaloids that are accumulated in response to various
      biotic and abiotic stresses including wounding. Mitogen activated protein (MAP)
      kinases are important components of cellular signaling system transducing these
      stress stimuli into intracellular responses by phosphorylation of downstream
      transcription factors, regulators or inhibitors leading to expression of stress
      responsive genes. Here, we report the activation of a 47 kDa MAP Kinase in C.
      roseus in response to wounding. The immunoprecipitation coupled with in-gel
      kinase assay revealed tyrosine phosphorylation of the protein. Partial
      purification of the MAP kinase was also attempted. We observed a size variation
      for the kinase when purified using different schemes.

PMID- 30184410
TI  - Assessment of respirable particulates in two residential areas of Kuwait State
      during dusty and nondusty storms: A time-series comparative study.
AB  - BACKGROUND: Kuwait State is branded by the recurrent dust storms and high
      pollution level. It has the highest dust concentration and surface temperature in
      Peninsula. The aim of the present study was to assess the respirable particulates
      during days with and without dust storms in two residential areas in Kuwait
      State. MATERIALS AND METHODS: This time-series comparative study was accomplished
      during the period from 1 January 2013 to 31 December 2013. It was conducted by
      recording the local meteorological data in the two sampling stations at Mansoria
      (A) and Ali Sabah Al-Salem (B) residential areas, in addition to the sampling and
      analysis of respirable particulates (PM10) using the SOP-10 High-Volume PM10
      Samplers' Standard Method. RESULTS: There were 256 and 278 measurement days (70.1
      and 75.1% of the yearly days) in monitoring stations A and B, respectively, with
      a total of 119 (46.5%) and 134 (48.2%) days with dust storms, respectively. The
      daily concentrations of PM10 were higher than the National Ambient Air Quality
      Standards of Kuwait State (150 MUg/m3) at the two stations. The annual PM10
      concentration of B station [192.5 (264.5) MUg/m3] was nonsignificantly higher
      than that of A [191.2 (182.7) MUg/m3]. At the two stations, the levels of PM10
      during days with dust storms were significantly higher than that during days
      without. CONCLUSION: Respirable particulate is slightly higher in Ali Sabah Al
      Salem than in Mansoria. Days with dust storms have significantly greater PM10
      levels than those without. The study recommends application of land-use planning,
      and windbreaks, combating desertification, and enhancing stoppage of outdoor
      activities during dust storms among public.

PMID- 30184412
TI  - In vitro screening of calli of mungbean to cercosporin, a photoactivated toxin.
AB  - Mungbean or Green gram [Vigna radiata (L.) R. Wilczek] is an arid/semiarid pulse
      crop, native to India, grown mostly as a rotational crop with cereals like wheat,
      rice, maize, sorghum, etc. It is an affordable source of protein, carbohydrate,
      vitamins and minerals preferred for its nutrient digestibility, food processing
      properties and bioavailability. India accounts for 65% of mungbean's world
      acreage and 54% of its world production. Various pests, diseases and
      environmental stresses have kept mungbean yield quite unstable over decades and
      researcher's worldover are looking for resistant varieties to overcome these
      challenges. Cercospora leaf spot (CLS) caused by Cercospora canescens is one of
      the most destructive diseases of mungbean and the key polyketide toxin
      cercosporin plays an important role in pathogenesis. Such toxins as selective
      agents in the tissue culture medium can help in selecting genotype with suitable
      levels of resistance to the toxin and/or to the pathogen among the available
      germplasm. Here, we standardized the dose of cercosporin for in vitro selection
      of resistant mungbean genotypes and variable expression of peroxidase, catalase
      and superoxide dismutase. Murashige and Skoog (MS) medium supplemented with 1.0
      mg L-1 NAA and 1.0 mg L-1 BAP was standardized for the development of callus from
      mungbean using hypocotyls as an explant. The calli from six cultivars of mungbean
      were tested in medium amended with cercosporin (0-40 ug mL-1) and calli survived
      up to 20 ug mL-1 of cercosporin. The calli from resistant cultivars survived
      83.33-93.00%, and showed lower reduction in fresh weight (25.97-28.83%). Calli
      from the susceptible cultivars survived 50-60% and showed higher reduction in
      fresh weight. Callus showed browning, exposure to cercosporin (5-20 ug mL-1).
      Enzymes assay from survived calli of different cultivars showed higher peroxidase
      activity (7.90-8.91 ?OD min-1 mg-1 callus), superoxide dismutase (0.96-1.03 ?OD
      min-1 mg-1 callus) and a lower catalase (0.35-0.43 u moles of H2O2 utilized min-1
      mg-1 callus) in resistant, followed by moderately resistance and susceptible
      cultivars. The necrosis in leaves was recorded with 200 ug mL-1 of cercosporin,
      and no visible necrosis was observed below this concentration. Enzyme assayed
      from the controlled and cercosporin-treated (100-200 ug mL-1) leaves of mungbean
      genotypes showed variable activity of peroxidase, catalase and superoxide
      dismutase.

PMID- 30184413
TI  - Effect of ethanolic extract of Quisqualis indica L. flower on experimental
      esophagitis in albino Wistar rats.
AB  - Quisqualis indica L., Syn. Combretum indicum (L.) DeFilipps., known as Rangoon
      creeper or Chinese Honeysuckle, is an abundant source of phenols and flavonoids
      thathave crucial role in free radical scavenging. Therefore, here we investigated
      whether extract of Q. indica flower has any role against esophagitis through
      scavenging of free radical oxygen species. In this study, we elucidated the
      effect of ethanolic flower extract of Q. indica on experimental esophagitis in
      albino Wister rats. The fasted animals divided into six groups and received
      carboxymethyl cellulose (CMC) (0.25%, 3 mL/kg, Sham control) or toxic control or
      pantoprazole (30 mg/kg) or flower extract of different doses (100, 200 and 300
      mg/kg) were subjected to pylorus and fore stomach ligation. All the animals were
      sacrificed after 8 h and evaluated for various parameters such as total acidity,
      free acidity, gastric pH, volume of gastric juices and esophagitis index.
      Esophageal tissues were subjected to estimation of various oxidative stress
      parameters like malonaldehyde (MDA), glutathione (GSH), catalase (CAT),
      superoxide dismutase (SOD) and protein carbonyl (PC). In a separate experiment,
      in vitro antioxidant assays such as DPPH and H2O2 assays, total phenolic and
      flavonoid contents were also conducted. The results revealed that treatments with
      pantoprazole and flower extracts significantly inhibited the gastric secretion,
      total acidity and esophagitis index. Various oxidative stress parameters also
      restored to normal level in the treated groups. This action could be due to the
      presence of higher phenolic and flavonoid contents. All these findings
      collectively suggest that the flower extract of Q. indica possibly possess anti
      esophagitis potential.

PMID- 30184414
TI  - In vitro macrophage activation: A technique for screening anti-inflammatory,
      immunomodulatory and anticancer activity of phytomolecules.
AB  - Macrophage activation plays a significant role in homeostasis of organisms.
      Various internal and external stress factors may affect their function, leading
      to adverse effects on the body. 'In vitro macrophage activation techniques
      provide us with a window to understand the mechanisms of inflammation and
      response of macrophages to the modulating interventions. Apart from infectious
      diseases, inflammation is also the major culprit in pathogenesis of many
      noncommunicable diseases such as arthritis, obesity, metabolic syndrome,
      diabetes, cancer, cardiovascular disease etc. In vitro macrophage activation
      allows us to study the role of polarized macrophages in the process of
      pathogenesis. This emerging technique leads to newer diagnostics, understanding
      pathophysiological mechanism/s, drug development and management of chronic
      inflammatory diseases. We, at MRC-KHS, use this technique for screening of
      medicinal plant-derived phytomolecules for their anti-inflammatory,
      immunomodulatory and anticancer activities. This review briefly outlines the
      different experimental models of in vitro macrophage activation and their
      applications for understanding the pathophysiological mechanisms of underlying
      chronic inflammation and screening of therapeutic activity of plant-based
      phytomolecules.

PMID- 30184415
TI  - Dietary ginger improves glucose dysregulation in a long-term high-fat high
      fructose fed prediabetic rat model.
AB  - The rapid increase in global diabetes burden with its associated morbidity and
      mortality is a major health concern for humans. Prediabetes is a condition which
      predispose a person not only to diabetes but also to the associated complications
      including morbidity even in the absence of an apparant hyperglycemia. However,
      appropriate dietary intervention may not only prevent but also improve one's
      condition as diet is the major contributor to such metabolic disorders. Here, we
      investigated the effect of dietary ginger (Zingiber officinale Roscoe) on the
      markers of insulin resistance and pathophysiology in a diet-induced prediabetic
      rat model. Male Sprague-Dawley (SD) rats were fed the following diets: control
      (5% groundnut oil + 65 % corn starch), high fat high fructose (HFHF; 25% beef
      tallow + 35 % fructose) and HFHF with 3 % ginger (HFHFG) for eight months. Plasma
      markers of insulin resistance, lipid profile, oral glucose tolerance (OGTT; 2nd
      and 5th month), intraperitoneal insulin tolerance (ITT), plasma total antioxidant
      capacity (TAC), liver histology and pancreatic immunohistochemistry (IHC) were
      examined. The impaired OGTT, ITT and insulin sensitivity indices with observed
      hyperinsulinemia and hypertriglyceridemia suggest that HFHF feeding resulted in
      prediabetes in rats. HFHF feeding also decreased insulin secretion in the
      pancreas, increased lipid accumulation in liver and total oxidants in plasma. The
      effects of HFHF feeding on glucose regulation, pathophysiology of pancreas and
      liver; total oxidative stress were improved by ginger feeding. The present study
      demonstrated thatlong-term HFHF feeding induces prediabetes in experimental rats
      while dietary ginger neutralizes the HFHF induced impairment in glucose
      regulation, dyslipidemia, and oxidative stress.

PMID- 30184416
TI  - Antioxidant, photosynthesis and growth characteristics of plants grown in high
      sulphur coalmine overburden.
AB  - North East region of India suffers from high sulphur coal mine overburden (OB)
      and plants those survive under such condition have adopted to such harsh
      environment. Here, we have investigated the effect of coal mine OB substrate on
      biochemical, physiological and growth of two shrubs Cassia (Cassia sofera L.) and
      Dhaincha (Sesbania rostrata L.); two tree species Gomari (Gmelina arborea L.) and
      Sisso (Dalbergia sisso L.); and two monocots Citronella Grass (Cymbopogon
      winterianus Jowitt) and Lemon Grass (Cymbopogon citratus L). The mine OB was
      found to be acidic (pH 2.0) with no true soil behavior, 12.5% sulphur and more
      than double the trace and heavy metals compared to normal control soil. Overall,
      high lipid peroxidation, membrane damage, peroxidase, glutathione reductase,
      ascorbate peroxidase, superoxide dismutase enzymes activities along with osmolyte
      proline and total soluble sugar was found in mine OB plants compared to control
      plants. While antioxidant activities were higher, nitrate reductase activity was
      significantly low but reduced leaf area, total shoot and root biomass. However,
      the responses of antioxidant activities in mine OB plants and control plants did
      not follow a standard pattern of higher activities in roots followed by old>young
      leaves or vice versa. Further, in mine OB plants, lipid peroxidation was found
      significantly higher for young citronella leaves. The levels of higher
      glutathione reductase was found in roots than the leaves except for old leaves in
      Gomari while ascorbate peroxidase was found in the leaves than the roots.
      Overall, all the species showed higher antioxidant enzyme activities, osmolyte
      accumulation and membrane damage possibly due to acidity and significantly higher
      limit of trace and heavy metals in mine OB substrate.

PMID- 30184417
TI  - Isolation of bacterial strains possessing nitrogen-fixation, phosphate and
      potassium-solubilization and their inoculation effects on sugarcane.
AB  - Inorganic nitrogen (N), phosphate (P) and potash (K) are the most influencing
      macro-nutrients for plant growth and microbial supplementation of these minerals
      through N2-fixation, P- and K-solubilization is gaining importance. In the
      present study, a macronutrient deficient (MD), N-free novel medium, supplemented
      with tri calcium phosphate (TCP as P- source) and Mica (as K- source) was used
      for isolation of microbes possessing nitrogen fixing, P- & K solubilizing
      abilities. Samples of rhizosphere and non-rhizosphere soils, roots and leaves of
      sugarcane varieties (viz., Co 6304, Co 86032 and CoC 671) collected from Tamil
      Nadu, India were used for isolation. Totally, 8 individual nitrogen-fixing,
      phosphate- and potash-solubilizing bacterial strains were obtained. Nitrogen
      fixing abilities of these isolates were confirmed by analyzing acetylene
      reduction (AR) activity and the presence of nif genes. P- and K- solubilizing
      activities were confirmed by cultivating these isolates in solid/liquid medium
      supplemented with insoluble forms of P and K. These isolates which produced
      growth hormone IAA, were in two groups as Roseateles terrae and Burkholderia
      gladioli, respectively based on the morphological, physiological, biochemical and
      16S rDNA gene sequence analysis. Association between diazotrophic, P- and K
      solubilizing R. terrae and B. gladioli with sugarcane has not been reported
      earlier. These isolates were tested for their growth-promoting abilities in
      sugarcane cultivated in pots, and the results showed that these isolates were
      able to increase the leaf chlorophyll, N content and total biomass. This study
      may encourage farmers to use single microbe for microbial supplementation of N, P
      and K instead of consortium of microbes wherein the compatibility between
      different microbes is often compromised.

PMID- 30184418
TI  - In vitro flowering in Bambusa bambos (L.) Voss, an anatomical perspective.
AB  - Bamboo [Bambusa bambos (L.) Voss (Syn. Bambusa arundinacea Retz.)] is an
      important arborescent grass with immense socio economic implications. The plant
      exhibits unique biological and growth characteristics including a distinct
      monocarpic gregarious flowering behavior. Studies on in vitro flowering in bamboo
      are not uncommon. The present study focuses on effect of different growth
      regulators on in vitro flowering in B. bambos and analyzes the morphological and
      developmental changes accompanying the process. Multiple shoots were raised from
      B. bambos seeds on MS medium supplemented with 10 MUM BAP. Anatomical sections
      showed intense mitotic activity in the apical meristem of the main shoot and
      formation of additional shoot buds along the margins. For multiplication,
      propagules of 7-9 shoots were transferred to maintenance medium containing 5 MUM
      BAP. Longitudinal sections of propagules showed prolific cell divisions and
      formation of meristemoids, which continuously gave rise to new shoots upon
      subculture. In vitro induction of flowering in cultures was observed in multiple
      shoots after 8 weeks. Transfer of multiple shoots to MS basal medium containing
      10 MUM NAA resulted in rooting and proliferation of inflorescences. On medium
      supplemented with 10 MUM 2,4-D callusing and development of shoot buds and
      somatic embryos was followed by development of inflorescences. The report
      outlines a protocol that can be used to raise and proliferate flowering cultures
      in B. bambos.

PMID- 30184419
TI  - RAPD analysis of long term micropropagated rootstock plants of Apple Malling 7.
AB  - Apple is the most dominating fruit crop of Himachal Pradesh, constituting about
      40 per cent of total area under fruit crops and about 90 per cent of the total
      fruit production. Plant tissue culture has encouraged production of quality
      planting material which is disease free and true to type. Due to current trends
      in favour of high density apple plantations and to fulfill the requirement of
      planting material from the farmers, commercially viable in vitro propagation
      method of semidwarf clonal apple rootstock Malling 7 (M7) was developed by
      axillary branching, initially developed from shoot tip explants. A few thousand
      plants were transferred to field conditions. In order to check any tissue culture
      induced variation in these long term micropropagated plants, the genetic fidelity
      was assessed using Random Amplified Polymorphic DNA (RAPD) markers. Out of the 20
      primers screened, 12 generated a total of 44 scorable and distinct bands with an
      average of 3.7 bands per primer. All the banding patterns for each primer were
      highly uniform and monomorphic across in vitro multiple shoot clusters and field
      transplanted micropropagated plants as well as comparable to the field grown
      mother clone from which the cultures had been established. Our results have shown
      that the micropropagation protocol developed by this study is appropriate and
      applicable for clonal propagation of apple rootstock M7 on large scale over a
      long period without any risk of genetic instability.

PMID- 30184420
TI  - Synergistic effect of silver nitrate and coconut water on shoot differentiation
      and plant regeneration from cultured cotyledons of Capsicum annuum L.
AB  - Chili pepper (Capsicum annuum L.) ranks among the most important vegetable crop
      belonging to the family Solanaceae that is consumed both as vegetable and spice
      throughout the world. C. annuum, as crop, in order to meet the target yield,
      demands improved variety that could overcome environmental challenges viz.,
      biotic and abiotic stress. Cultivar improvement essentially requires an efficient
      in vitro regeneration protocol. In the present study, we investigated the
      influence of silver nitrate (AgNO3) and coconut water, individually as well in
      combination, on in vitro shoot elongation and plant regeneration from cotyledon
      explants of C. annuum cv G-4. Shoot buds were induced on shoot bud induction
      medium supplemented with either 44.38 uM 6-benzylaminopurine (BAP) or 9.0 uM
      thidiazuron (TDZ) along with 5.77 uM gibberellic acid (GA3) and 14.7 uM phenyl
      acetic acid (PAA). Elongation of shoot buds was obtained on elongation medium
      containing 8.87 uM BA or 0.45 uM TDZ, 5.77 uM GA3 and 14.7 uM PAA followed by
      rooting in 9.8 uM indole-3-butyric acid (IBA). All the media were supplemented
      with 30 uM AgNO3 and/or coconut water (10% v/v). The presence of coconut water in
      the elongation media enhanced the regeneration of well developed shoots from
      differentiating explants on TDZ media while AgNO3 resulted in enhanced production
      of rooted shoots with greater influence on emerging shoots from BAP media upon
      transfer to rooting media. There was synergistic response with further
      enhancement of elongated shoots/elongated rooted shoots on the combined use of
      coconut water and AgNO3. The elongation media produced significantly higher total
      shoots when AgNO3 was used synergistically with coconut water (59.0%) as against
      AgNO3 alone (38.0%). While in rooting media, there was significantly higher
      production of elongated rooted shoots when coconut water was used synergistically
      with AgNO3 (47.2%) as against the coconut water alone (14.4%).

PMID- 30184421
TI  - Optimization of process parameters for bioproduction, isolation and purification
      of 4-Ipomeanol from cell suspension cultures of Ipomoea batatas (L.) Lam.
AB  - The secondary metabolite, 4-Ipomeanol from Sweet potato (Ipomoea batatas) is a
      potential chemotherapeutic agent for cancer. This study presents an efficient
      protocol for bioproduction of 4-ipomeanol, in large quantities without disturbing
      the natural biodiversity of I. batatas. Friable Calli from the root tubers of I.
      batatas were used to establish cell suspension cultures in liquid media under
      agitated conditions and the growth and production kinetics of the same were
      monitored. The presence of 4-ipomeanol was confirmed by NMR and IR spectroscopy
      and quantification was done using HPLC. A maximum of 7.39 mg g-1 of 4-ipomeanol
      was obtained under biotic elicitation of the cell suspension cultures. The
      elicitors were studied for optimization of the day of addition and maximum
      bioproduction of 4-ipomeanol was observed when elicitors were added to 4 day old
      suspension cultures. Further, the 4-ipomeanol thus produced demonstrated
      cytotoxicity against renal carcinoma cell lines.

PMID- 30184422
TI  - Metal (Au, Pt) Nanoparticle-Latex Nanocomposites as Probes for
      Immunochromatographic Test Strips with Enhanced Sensitivity.
AB  - The development of a sensitive and rapid diagnostic test for early detection of
      infectious viruses is urgently required to defend against pandemic and infectious
      diseases including seasonal influenza. In this study, we developed noble metal
      (Au, Pt) nanoparticle-latex nanocomposite particles for use as probes for
      immunochromatographic test (ICT) strips. The nanocomposite particles were
      conjugated with monoclonal antibody (mAb) to detect an influenza A (H1N1)
      antigen. For comparison, Au nanoparticles conjugated with mAb were also prepared.
      The lowest detectable concentrations of the influenza A antigen were found to be
      6.25 * 10-3 and 2.5 * 10-2 HAU/mL for Au nanoparticle-latex and Pt nanoparticle
      latex nanocomposite particles, respectively, whereas it was 4.0 * 10-1 HAU/mL for
      Au nanoparticles. These results clearly demonstrated that the nanocomposite
      probes were more sensitive than conventional nanoparticle-based probes for ICT.
      To expand the versatility of the nanocomposite probes, the surfaces of the probes
      were functionalized with biotinylated proteins to enable modification of their
      surfaces with desired biotinylated antibodies through biotin-avidin binding.

PMID- 30184423
TI  - sp3 C-H Arylation and Alkylation Enabled by the Synergy of Triplet Excited
      Ketones and Nickel Catalysts.
AB  - Triplet ketone sensitizers are of central importance within the realm of
      photochemical transformations. Although the radical-type character of triplet
      excited states of diaryl ketones suggests the viability for triggering hydrogen
      atom transfer (HAT) and single-electron transfer (SET) processes, among others,
      their use as multifaceted catalysts in C-C bond-formation via sp3 C-H
      functionalization of alkane feedstocks still remains rather unexplored. Herein,
      we unlock a modular photochemical platform for forging C( sp3)-C( sp2) and C(
      sp3)-C( sp3) linkages from abundant alkane sp3 C-H bonds as functional handles
      using the synergy between nickel catalysts and simple, cheap and modular diaryl
      ketones. This method is distinguished by its wide scope that is obtained from
      cheap catalysts and starting precursors, thus complementing existing inner-sphere
      C-H functionalization protocols or recent photoredox scenarios based on iridium
      polypyridyl complexes. Additionally, such a platform provides a new strategy for
      streamlining the synthesis of complex molecules with high levels of predictable
      site-selectivity and preparative utility. Mechanistic experiments suggest that
      sp3 C-H abstraction occurs via HAT from the ketone triplet excited state. We
      believe this study will contribute to a more systematic utilization of triplet
      excited ketones as catalysts in metallaphotoredox scenarios.

PMID- 30184424
TI  - Quaternary Amine-Terminated Quantum Dots Induce Structural Changes to Supported
      Lipid Bilayers.
AB  - The cytoplasmic membrane represents an essential barrier between the cytoplasm
      and the environment external to cells. Interaction with nanomaterials can alter
      the integrity of the cytoplasmic membrane through the formation of holes and
      membrane thinning, which can ultimately lead to adverse biological impacts. Here
      we use supported lipid bilayers as experimental models for the cytoplasmic
      membrane to investigate the impact of quantum dots functionalized with the
      cationic polymer poly(diallyldimethylammonium chloride) (PDDA) on membrane
      structure. Using a quartz crystal microbalance with dissipation monitoring we
      show that the positively charged quantum dots attach to and induce structural
      rearrangement to zwitterionic bilayers in solely the liquid-disordered phase and
      in those containing phase-segregated liquid-ordered domains. Real-time atomic
      force microscopy imaging revealed that PDDA-coated quantum dots and, to a lesser
      extent, PDDA itself induced the disappearance of liquid-ordered domains. We
      hypothesize this effect is due to an increase in energy per unit area caused by
      collisions between PDDA-coated quantum dots at the membrane surface. This
      increase in free energy per area exceeds the approximate free-energy change
      associated with membrane mixing between the liquid-ordered and liquid-disordered
      phases and results in the destabilization of membrane domains.

PMID- 30184425
TI  - Biocompatible Meshes with Appropriate Wettabilities for Underwater Oil
      Transportation/Collection and Highly Effective Oil/Water Separation.
AB  - In this study, we prepared biocompatible superhydrophilic and underwater
      superoleophobic tannic acid (TA)/polyvinylpyrrolidone (PVP)-coated stainless
      steel meshes that mediated extremely efficient separations of mixtures of oil and
      water. These TA/PVP-coated stainless-steel meshes displayed excellent antifouling
      properties and could be used to separate oil/water mixtures continuously for up
      to 24 h. Moreover, a funnel-like TA/PVP-coated stainless-steel mesh device could
      be used for underwater oil transportation and collection. In conjunction with our
      continuous oil removal system, this device allowed for the continuous collection
      and removal of oil pollutants from underwater environments. The high performance
      of these TA/PVP-coated stainless-steel meshes and their green, low-energy, cost
      effective preparation suggests great potential for practical applications.

PMID- 30184426
TI  - Polyurethane Microparticles for Stimuli Response and Reduced Oxidative
      Degradation in Highly Porous Shape Memory Polymers.
AB  - Shape memory polymers (SMPs) have been found to be promising biomaterials for a
      variety of medical applications; however, the clinical translation of such
      technology is dependent on tailorable properties such as gravimetric changes in
      degradation environments. For SMPs synthesized from amino-alcohols, oxidation
      resulting in rapid mass loss may be problematic in terms of loss of material
      functionality as well as toxicity and cytocompatibility concerns. Control of
      gravimetric changes was achieved through the incorporation of small molecule
      antioxidants, either directly into the polymer matrix or included in
      microparticles to form a SMP composite material. With direct incorporation of
      small molecule phenolic antioxidant 2,2'-methylenebis(6- tert-butyl)-methylphenol
      (Methyl), SMPs displayed reduce strain recovery by more than 50% (Methyl) and
      increase elastic modulus from approximately 1.4 to 2.3 MPa, at the expense of the
      strain to failure being reduced from 45% to 32%. Importantly, such changes could
      not ensure retention of the antioxidants and therefore did not increase oxidative
      stability beyond 15 days in accelerated oxidative conditions (equivalent to
      approximately 800 days in porcine aneurysms) in all cases except for the
      inclusion of a hindered amine that capped network growth, which also resulted in
      shape memory reduction (only 80% recoverable strain achieved). However, the
      inclusion of antioxidants in microparticles was found to produce materials with
      similar thermomechanical ( Tg migration below 1.0  degrees C) and shape recovery
      of 100%, while increasing oxidative resistance compared to controls (oxidation
      onset was delayed by 3 days and material lifespan increased to approximately 20
      22 days in accelerated oxidative solution or beyond 1000 days in the porcine
      aneurysm). The microparticle composite SMPs also act as a platform for
      environmental sensing, such as pH-dependent fluorescence shifts and payload
      release, as demonstrated by fluorescent dye studies using phloxine B and nile
      blue chloride and the release of antioxidants over a 3 week period. The use of
      polyurethane-urea microparticles in porous SMPs is demonstrated to increase
      biostability of the materials, by approximately 25%, and ultimately extend their
      lifespan for use in aneurysm occlusion as determined through calculated in vivo
      degradation rates corresponding to a porcine aneurysm environment.

PMID- 30184427
TI  - Fabrication of Liquid-Crystal-Based Optical Sensing Platform for Detection of
      Hydrogen Peroxide and Blood Glucose.
AB  - Rapid and accurate determination of H2O2 is of great importance in practical
      applications. In this study, we demonstrate construction of liquid-crystal (LC)
      based sensing platforms for sensitive and real-time detection of H2O2 with high
      accuracy for the first time. Single-stranded DNA (ssDNA) adsorbed onto the
      surface of nanoceria is released to the aqueous solution in the presence of H2O2,
      which disrupts arrangement of the self-assembled cationic surfactant monolayer
      decorated at the aqueous/LC interface. Thus, the orientation of LCs changes from
      a homeotropic to planar state, leading to change in the optical response from
      dark-to-bright appearance. As H2O2 can be produced during oxidation of glucose by
      glucose oxidase (GOx), detection of glucose is also fulfilled by employing the
      H2O2 sensing platform. Our system can detect H2O2 and glucose with concentrations
      as low as 28.9 nM and 0.52 MUM, respectively. It shows high promise of using LC
      based sensors for the detection of H2O2 and its relevant biomarkers in practical
      applications.

PMID- 30184428
TI  - Comment on "Negative Deviations from the Debye-Huckel Limiting Law for High
      Charge Polyvalent Electrolytes: Are They Real?"
AB  - A work ( Fraenkel , D. J. Chem. Theory Comput. 2018 , 14 , 2609 , DOI:
      10.1021/acs.jctc.7b01260 ) was recently published in which, starting from data of
      activity coefficients of electrolytes determined by Malatesta and co-workers in
      the years 1992-2000, an incorrect conclusion is reached, i.e., that the negative
      deviations from the Debye-Huckel limiting law found at high dilution for high
      charge polyvalent electrolytes were presumably not real. The present work shows
      the reasons why we cannot share his opinion. The negative deviations are
      supported both by the theory and by experimental demonstration.

PMID- 30184429
TI  - Occupancies in the DNA-Binding Pathways of Intrinsically Disordered Helix-Loop
      Helix Leucine-Zipper Proteins.
AB  - Quantifying the stability of intermediates along parallel molecular pathways is
      often hampered by the limited experimental resolution of ensemble methods. In
      biology, however, such intermediates may represent important regulatory targets,
      thus calling for strategies to map their abundance directly. Here, we use single
      molecule Forster resonance energy transfer (FRET) to quantify the occupancies of
      intermediates along two parallel DNA-binding pathways of the basic helix-loop
      helix leucine-zipper (bHLH-LZ) domains of the transcription factors c-Myc and
      Max. We find that both proteins are intrinsically disordered with sub-microsecond
      end-to-end distance dynamics. In mixtures of the proteins with their promoter
      DNA, our experiments identify the disordered conformers, the folded Myc-Max
      dimer, and ternary Myc-Max-DNA complexes. However, signatures of the intermediate
      along the alternative pathway, i.e., one domain bound to DNA, remained
      undetectable. This implies that disordered Max-DNA and Myc-DNA complexes are by
      at least 6 kB T higher in free energy than folded dimers of Myc and Max. The
      disordered monomer-DNA complex is therefore unlikely to be of importance for the
      regulation of transcriptional processes.

PMID- 30184430
TI  - Janus N-Doped Carbon@Silica Hollow Spheres as Multifunctional Amphiphilic
      Nanoreactors for Base-Free Aerobic Oxidation of Alcohols in Water.
AB  - The hydrophobicity/hydrophilicity of nanocatalysts has a significant impact on
      their performances via modulating the adsorption, transfer, and desorption of
      reactants/products. In this work, we reported a novel multifunctional amphiphilic
      nanoreactor composed of Janus nitrogen-doped carbon@silica hollow nanostructure
      and ultrasmall Pt nanoparticles. The core/shell polybenzoxazine@mesosilica
      spheres were used as the precursor for pyrolysis. It was found that the internal
      polybenzoxazine was decomposed from interior to exterior and transformed into a
      nitrogen-doped carbon hollow shell that partly embedded into the mesosilica
      layer, forming the Janus hollow spheres. The obtained nanoreactor showed
      remarkable activity and selectivity for base-free aerobic oxidation of alcohols
      in water using air as the oxidant. A one-pot oxidation-condensation cascade
      reaction was also successfully demonstrated to synthesize imines from alcohols
      and amines with good yields. The sorption analyses revealed that the superior
      hydrophilicity/hydrophobicity strengthened both adsorption of hydrophobic
      alcohols from water and desorption of byproduct water molecules from the active
      sites. The doped nitrogen atoms in the carbon matrix were used not only as
      anchoring sites for stabilizing ultrasmall Pt nanoparticles but also as basic
      active sites for accelerating the deprotonation process. Moreover, due to the
      anchoring effect of nitrogen and the extremely stable amphiphilicity, this
      nanoreactor exhibited excellent catalytic stability.

PMID- 30184431
TI  - Curcumin-Loaded Liquid Crystalline Systems for Controlled Drug Release and
      Improved Treatment of Vulvovaginal Candidiasis.
AB  - Vulvovaginal candidiasis (VVC) is the most common infection caused by Candida
      albicans and greatly reduces the quality of life of women affected by it. Due to
      the ineffectiveness of conventional treatments, there is growing interest in
      research involving compounds of natural origin. One such compound is curcumin
      (CUR), which has been proven to be effective against this microorganism. However,
      some of CUR's physicochemical properties, especially its low aqueous solubility,
      make the therapeutic application of this compound difficult. Thus, the
      incorporation of CUR in mucoadhesive liquid crystalline systems (MLCSs) for
      vaginal administration may be an efficient strategy for the treatment of VVC.
      MLCSs are capable of potentiating the compound's action, releasing it in a
      controlled manner, and can enable longer exposure at the site of infection. In
      this study, MLCSs consisting of oleic acid and ergosterol 5:1 (w/w) as the oily
      phase, PPG-5-CETETH-20 as the surfactant, and a polymer dispersion of 1% chitosan
      as the aqueous phase, were developed for the application of CUR (MLCS-CUR) in VVC
      treatment. The formulations were characterized by polarized light microscopy
      (PLM), small-angle X-ray scattering (SAXS), oscillatory rheometry, continuous
      shear rheometry, texture profile analysis, and in vitro mucoadhesion. In
      addition, the antimicrobial activity was evaluated in vitro, and the effects on
      local fungal burden and cytokine profiles were investigated in a murine model of
      VVC. PLM and SAXS showed that the developed formulations presented a
      characteristic of a microemulsion. However, after the addition of artificial
      vaginal mucus (AVM), PLM showed that the formulations had structures similar to
      the "Maltese cross" characteristic of lamellar MLCS. Mucoadhesive test results
      showed an increase in the mucoadhesive strength of these formulations. Rheology
      analyses suggested long-lasting action of the formulation at the infected site.
      The in vitro antimicrobial activity assays suggested that CUR possesses
      antifungal activity against Candida albicans, determined after its incorporation
      into the MLCS. Further, MLCS-CUR was also more effective in vivo in the control
      of vaginal infection than treatment with fluconazole. Immunological assays showed
      that the ratio of pro-inflammatory (IL-1beta) to anti-inflammatory (TGF-beta)
      cytokines has decreased and that there is a reduction in the number of
      polymorphonuclear neutrophils recruited to the vaginal lumen, showing that
      treatment with MLCS-CUR was effective in modulating the inflammatory reaction
      associated with the infection. The results suggest that MLCSs could potentially
      be used in the treatment of VVC with CUR.

PMID- 30184432
TI  - Photoinduced Reconfiguration of Complex Emulsions Using a Photoresponsive
      Surfactant.
AB  - Photoresponsive complex emulsions are prepared in a three-phase system consisting
      of two oils: hexane (H) and perfluorooctane (F). An aqueous solution of a mixed
      surfactant of fluorosurfactant, F(CF2) x(CH2CH2O) yH (Zonyl FS-300), and a
      synthesized light-responsive surfactant, 2-(4-(4
      butylphenyl)diazenylphenoxy)ethyltrimethylammonium bromide (C4AZOC2TAB) was
      employed as the continuous phase. Complex emulsions with various geometries were
      prepared by one-step vortex mixing and a temperature-induced phase-separation
      method. It was noticed that the topology of the complex emulsion was highly
      dependent on the mass ratio of Zonyl FS-300/C4AZOC2TAB. Light microscopy images
      showed that phase inversion from an H/F/W- to an F/H/W-type double emulsion via a
      Janus emulsion was achieved by gradually increasing the mass ratio of
      C4AZOC2TAB/Zonyl FS-300. Upon UV/blue light irradiation, the topology of complex
      emulsions was turned to switch from an F/H/W double emulsion to a Janus emulsion
      to an entirely inverted H/F/W double emulsion. Dynamic interfacial tension
      measurements showed that UV irradiation of the interface between an aqueous trans
      C4AZOC2TAB solution and hexane brings about an increase in the interfacial
      tension, suggesting the nature of photoinduced morphological changes in complex
      emulsions. The reconfiguration process of complex emulsions was illustrated by
      the Marangoni effect based on heterogeneity in the interfacial tension at the
      complex emulsion surface induced by controlling the molecular conversion of
      C4AZOC2TAB using light irradiation. Finally, we used the complex emulsions
      structure to form an on-off switch to start and shut off the evaporation of one
      volatile phase to achieve process monitoring. This could be used to initiate and
      quench a reaction, which offers a novel idea for achieving switchable and
      reversible reaction control in multiple-phase reactions.

PMID- 30184433
TI  - Synthesis and Evaluation of a Mitochondria-Targeting Poly(ADP-ribose) Polymerase
      1 Inhibitor.
AB  - The poly(ADP-ribose) polymerase (PARP) family of enzymes plays a crucial role in
      cellular and molecular processes including DNA damage detection and repair and
      transcription; indeed, PARP inhibitors are under clinical evaluation as
      chemotherapeutic adjuncts given their capacity to impede genomic DNA repair in
      tumor cells. Conversely, overactivation of PARP can lead to NAD+ depletion,
      mitochondrial energy failure, and cell death. Since PARP activation facilitates
      genomic but impedes mitochondrial DNA repair, nonselective PARP inhibitors are
      likely to have opposing effects in these cellular compartments. Herein, we
      describe the synthesis and evaluation of the mitochondria-targeting PARP
      inhibitor, XJB-veliparib. Attachment of the hemigramicidin S pentapeptide
      isostere for mitochondrial targeting using a flexible linker at the primary amide
      site of veliparib did not disrupt PARP affinity or inhibition. XJB-veliparib was
      effective at low nanomolar concentrations (10-100 nM) and more potent than
      veliparib in protection from oxygen-glucose deprivation (OGD) in primary cortical
      neurons. Both XJB-veliparib and veliparib (10 nM) preserved mitochondrial NAD+
      after OGD; however, only XJB-veliparib prevented release of NAD+ into cytosol.
      XJB-veliparib (10 nM) appeared to inhibit poly(ADP-ribose) polymer formation in
      mitochondria and preserve mitochondrial cytoarchitecture after OGD in primary
      cortical neurons. After 10 nM exposure, XJB-veliparib was detected by LC-MS in
      mitochondria but not nuclear-enriched fractions in neurons and was observed in
      mitoplasts stripped of the outer mitochondrial membrane obtained from HT22 cells.
      XJB-veliparib was also effective at preventing glutamate-induced HT22 cell death
      at micromolar concentrations. Importantly, in HT22 cells exposed to H2O2 to
      produce DNA damage, XJB-veliparib (10 MUM) had no effect on nuclear DNA repair,
      in contrast to veliparib (10 MUM) where DNA repair was retarded. XJB-veliparib
      and analogous mitochondria-targeting PARP inhibitors warrant further evaluation
      in vitro and in vivo, particularly in conditions where PARP overactivation leads
      to mitochondrial energy failure and maintenance of genomic DNA integrity is
      desirable, e.g., ischemia, oxidative stress, and radiation exposure.

PMID- 30184434
TI  - Sequentially Reinforced Additive Coating for Transparent and Durable
      Superhydrophobic Glass.
AB  - Now that there are various routes to prepare superhydrophobic surfaces for self
      cleaning, anti-icing, liquid collecting, etc., attentions are moving toward low
      cost upscaling of routes and increasing the reliability for actual applications.
      However, the required micro-nano structures for superhydrophobicity are light
      scattering and very vulnerable to abrasion. This intrinsically conflicts with the
      transparency and durability of superhydrophobic glass, which are the major
      barriers for its commercialization. In this study, we present a novel
      sequentially reinforced additive coating (SRAC) process to realize robust and
      transparent micro-nano structured film with tough intergranular sintering. A
      benign aqueous-based ink with poly(furfuryl alcohol) (PFA) and silica species is
      carefully designed and sprayed on glass to enable self-phase separation and
      morphology construction. The coatings reach the static contact angle (SCA) for
      water over 166 degrees  and withstand a 6H pencil scratching, the cross-cut test,
      and sand abrasion. Moreover, we also performed a 90 day outdoor performance test
      and the glass maintained superhydrophobicity with an SCA of 154 degrees . These
      results provide a low-cost waterborne ink formula, and the high throughput and
      upscalable SRAC process could be a convenient technology for the fabrication of
      large area, robust superhydrophobic coatings.

PMID- 30184436
TI  - Molecular Insights into Human Hereditary Apolipoprotein A-I Amyloidosis Caused by
      the Glu34Lys Mutation.
AB  - Hereditary apolipoprotein A-I (apoA-I) amyloidosis is a life-threatening
      incurable genetic disorder whose molecular underpinnings are unclear. In this
      disease, variant apoA-I, the major structural and functional protein of high
      density lipoprotein, is released in a free form, undergoes an alpha-helix to
      intermolecular cross-beta-sheet conversion along with a proteolytic cleavage, and
      is deposited as amyloid fibrils in various organs, which can cause organ damage
      and death. Glu34Lys is the only known charge inversion mutation in apoA-I that
      causes human amyloidosis. To elucidate the structural underpinnings of the
      amyloidogenic behavior of Glu34Lys apoA-I, we generated its recombinant globular
      N-terminal domain (residues 1-184) and compared the conformation and dynamics of
      its lipid-free form with those of two other naturally occurring apoA-I variants,
      Phe71Tyr (amyloidogenic) and Leu159Arg (non-amyloidogenic). All variants showed
      reduced structural stability and altered aromatic residue packing. The greatest
      decrease in stability was observed in the non-amyloidogenic variant, suggesting
      that amyloid formation is driven by local structural perturbations at sensitive
      sites. Molecular dynamics simulations revealed local helical unfolding and
      suggested that transient opening of the Trp72 side chain induced mutation
      dependent structural perturbations in a sensitive region, including the major
      amyloid hot spot residues Leu14-Leu22. We posit that a shift from the "closed" to
      the "open" orientation of the Trp72 side chain modulates structural protection of
      amyloid hot spots, suggesting a previously unknown early step in the protein
      misfolding pathway.

PMID- 30184435
TI  - Fast Open Modification Spectral Library Searching through Approximate Nearest
      Neighbor Indexing.
AB  - Open modification searching (OMS) is a powerful search strategy that identifies
      peptides carrying any type of modification by allowing a modified spectrum to
      match against its unmodified variant by using a very wide precursor mass window.
      A drawback of this strategy, however, is that it leads to a large increase in
      search time. Although performing an open search can be done using existing
      spectral library search engines by simply setting a wide precursor mass window,
      none of these tools have been optimized for OMS, leading to excessive runtimes
      and suboptimal identification results. We present the ANN-SoLo tool for fast and
      accurate open spectral library searching. ANN-SoLo uses approximate nearest
      neighbor indexing to speed up OMS by selecting only a limited number of the most
      relevant library spectra to compare to an unknown query spectrum. This approach
      is combined with a cascade search strategy to maximize the number of identified
      unmodified and modified spectra while strictly controlling the false discovery
      rate as well as a shifted dot product score to sensitively match modified spectra
      to their unmodified counterparts. ANN-SoLo achieves state-of-the-art performance
      in terms of speed and the number of identifications. On a previously published
      human cell line data set, ANN-SoLo confidently identifies more spectra than
      SpectraST or MSFragger and achieves a speedup of an order of magnitude compared
      with SpectraST. ANN-SoLo is implemented in Python and C++. It is freely available
      under the Apache 2.0 license at https://github.com/bittremieux/ANN-SoLo .

PMID- 30184437
TI  - Plastron Regeneration on Submerged Superhydrophobic Surfaces Using In Situ Gas
      Generation by Chemical Reaction.
AB  - Superhydrophobic surfaces submerged under water appear shiny due to total
      internal reflection of light from a thin layer of air (plastron) trapped in their
      surface texture. This entrapped air is advantageous for frictional drag reduction
      in various applications ranging from microfluidic channels to marine vessels.
      However, these aerophilic textures are prone to impregnation by water due to
      turbulent pressure fluctuations from external flows and dissolution of the
      trapped gas into the water. We demonstrate a novel chemical method to replenish
      the plastron in situ by using the decomposition reaction of hydrogen peroxide on
      superhydrophobic surfaces prepared with a catalytic coating. We also provide a
      thermodynamic framework for designing superhydrophobic surfaces with optimal
      texture and chemistry for underwater plastron regeneration. We finally
      demonstrate the practical utility of this method by fabricating periodic
      microtextures on aluminum surfaces that incorporate a cheap catalyst, manganese
      dioxide. We perform drag-reduction experiments under turbulent flow conditions in
      a Taylor-Couette cell (TC cell), which show that more than half of the drag
      increase ensuing from plastron collapse can be recovered spontaneously by
      injection of dilute H2O2 into the TC cell. Thus, we present a low-cost, scalable
      method to enable in situ plastron regeneration on large surfaces for marine
      applications.

PMID- 30184438
TI  - Interaction of Insulin-Like Growth Factor-Binding Protein 3 With Hyaluronan and
      Its Regulation by Humanin and CD44.
AB  - Insulin-like growth factor-binding protein-3 (IGFBP-3) belongs to a family of IGF
      binding proteins. Humanin is a peptide known to bind residues 215-232 of mature
      IGFBP-3 in the C-terminal region of the protein. This region of IGFBP-3 was shown
      earlier to bind certain glycosaminoglycans including hyaluronan (HA). Here, we
      characterized the binding affinities of the IGFBP-3 protein and peptide (215
      KKGFYKKKQCRPSKGRKR-232) to HA and to humanin and found that HA binds with a
      weaker affinity to this region than does humanin. Either HA or humanin could bind
      to this IGFBP-3 segment, but not simultaneously. The HA receptor, CD44, blocked
      HA binding to IGFBP-3 but had no effect on binding of humanin to either IGFBP-3
      or its peptide. Upon incubation of HA with CD44 and either IGFBP-3 protein or
      peptide, humanin was effective at binding and sequestering IGFBP-3 or peptide,
      thereby enabling access of CD44 to HA. We show that IGFBP-3 and humanin in the
      medium of A549 lung cancer cells can immunoprecipitate in a complex. However, the
      fraction of IGFBP-3 in the medium that is able to bind HA was not complexed with
      humanin suggesting that HA binding to the 215-232 segment renders it inaccessible
      for binding to humanin. Moreover, while the cytotoxic effects of IGFBP-3 on cell
      viability were reversed by humanin, blocking HA-CD44 interaction with an anti
      CD44 antibody in combination with IGFBP-3 did not have an additive negative
      effect on cell viability suggesting that IGFBP-3 exerts its cytotoxic effects on
      cell survival through a mechanism that depends on HA-CD44 interactions.

PMID- 30184439
TI  - Detecting genetic regions associated with height in the native ponies of the
      British Isles by using high density SNP genotyping.
AB  - Height is an important characteristic in the equine industry although little is
      known about its genetic control in native British breeds of ponies. This study
      aimed to map QTL data with the withers height in four pony breeds native to the
      British Isles, including two different sections within Welsh Cobs. In this study,
      a genome-wide analysis approach using the Illumina EquineSNP50 Infinium BeadChip
      was applied to 105 ponies and cobs. Analysis identified 222 highly significant
      height-associated SNPs (P <= 10-5), among which three SNPs on ECA9 have also been
      previously reported elsewhere. The highest number of significant SNPs associated
      to height in the native British horses were located on ECA1, ECA8, and ECA16.

PMID- 30184440
TI  - Draft genome sequence, disease-resistance genes, and phenotype of a Paenibacillus
      terrae strain (NK3-4) with the potential to control plant diseases.
AB  - Paenibacillus terrae NK3-4 is a plant growth-promoting rhizobacterium that may be
      useful for controlling plant diseases. We conducted a genomic analysis and
      identified the genes mediating antimicrobial functions. Additionally, an
      extracellular antifungal protein component was isolated and identified. The draft
      genome sequence was assembled into 54 contigs, with 5 458 568 bp and a G+C
      content of 47%. Moreover, 4 690 015 bp encoded 5090 proteins, 7 rRNAs, and 54
      tRNAs. Forty-four genes involved in antimicrobial functions were detected. They
      mainly encode 19 non-ribosomal peptide synthetases (NRPSs); one polyketide
      synthase/NRPSs hybrid enzyme; four Zn-dependent metalloproteases; three
      antilisterial bacteriocin subtilosin biosynthesis proteins (AlbA); four serine
      proteases; five pectate lyases; three beta-glucanases; and four 1,4-beta
      xylanases. These include four novel NRPSs that have not been found in any species
      of Paenibacillus. Furthermore, five proteins exhibiting antifungal activity were
      identified from the antifungal extracellular protein component based on MS/MS and
      the strain NK3-4 predicted protein library. On the basis of these features, we
      propose that strain NK3-4 represents a promising biocontrol agent for protecting
      plant from diseases. The draft genome sequence described herein may provide the
      genetic basis for the characterization of the molecular mechanisms underlying the
      biocontrol functions. It may also facilitate the development of rational
      strategies for improving the strain.

PMID- 30184442
TI  - "Precision" Public Health - Between Novelty and Hype.

PMID- 30184441
TI  - Identification of Primary Natural Killer Cell Modulators by Chemical Library
      Screening with a Luciferase-Based Functional Assay.
AB  - Natural killer (NK) cells are essential players of the innate immune response
      that secrete cytolytic factors and cytokines such as IFN-gamma when contacting
      virus-infected or tumor cells. They represent prime targets in immunotherapy as
      defects in NK cell functions are hallmarks of many pathological conditions, such
      as cancer and chronic infections. The functional screening of chemical libraries
      or biologics would greatly help identify new modulators of NK cell activity, but
      commonly used methods such as flow cytometry are not easily scalable to high
      throughput settings. Here we describe an efficient assay to measure the natural
      cytotoxicity of primary NK cells where the bioluminescent enzyme NanoLuc is
      constitutively expressed in the cytoplasm of target cells and is released in co
      culture supernatants when lysis occurs. We fully characterized this assay using
      either purified NK cells or total peripheral blood mononuclear cells (PBMCs),
      including some patient samples, as effector cells. A pilot screen was also
      performed on a library of 782 metabolites, xenobiotics, and common drugs, which
      identified dextrometorphan and diphenhydramine as novel NK cell inhibitors.
      Finally, this assay was further improved by developing a dual-reporter cell line
      to simultaneously measure NK cell cytotoxicity and IFN-gamma secretion in a
      single well, extending the potential of this system.

PMID- 30184443
TI  - Microbial communities associated with barley growing in an oil sands reclamation
      area in Alberta, Canada.
AB  - Microbial communities that colonize the plant rhizosphere and the root interior
      can ameliorate plant stress and promote growth. These plant-microbe associations
      are being investigated to assist in reclamation soils in northern Alberta. This
      study assessed the diversity of bacterial species associated with barley plants
      growing at different cover managements and slope positions in an oil sands
      reclamation area. Phospholipid fatty acid analysis of the microbial communities
      indicated that both cover type and slope, in addition to soil total and organic
      carbon, NH4+, and organic matter, were significant determinants of microbial
      community composition. However, analysis of denaturing gel gradient
      electrophoresis (DGGE) banding patterns revealed that while most bulk and
      rhizosphere soils differentiated by cover management, no clustering was observed
      in endophytes. In addition, techniques to assess culture-dependent endophytic
      bacteria revealed a dominance of the class Gammaproteobacteria, in which
      Enterobacteriaceae (44%), Xanthomonaceae (30%), and Pseudomonaceae (26%) were the
      most abundant families in this class. Several endophytic isolates also matched
      those from DGGE profiles. The results of this study suggest that plants growing
      on oil sands reclamation covers host a wide range of bacterial endophytes, which
      should be assessed as to their potential to assist plant establishment and growth
      at such sites.

PMID- 30184444
TI  - DNA barcodes reveal deeply neglected diversity and numerous invasions of
      micromoths in Madagascar.
AB  - Madagascar is a prime evolutionary hotspot globally, but its unique biodiversity
      is under threat, essentially from anthropogenic disturbance. There is a race
      against time to describe and protect the Madagascan endangered biota. Here we
      present a first molecular characterization of the micromoth fauna of Madagascar.
      We collected 1572 micromoths mainly using light traps in both natural and
      anthropogenically disturbed habitats in 24 localities across eastern and
      northwest Madagascar. We also collected 1384 specimens using a Malaise trap in a
      primary rain forest at Andasibe, eastern Madagascar. In total, we DNA barcoded
      2956 specimens belonging to 1537 Barcode Index Numbers (BINs), 88.4% of which are
      new to BOLD. Only 1.7% of new BINs were assigned to species. Of 47 different
      families found, Dryadaulidae, Bucculatricidae, Bedelliidae, Batrachedridae, and
      Blastobasidae are newly reported for Madagascar and the recently recognized
      Tonzidae is confirmed. For test faunas of Canada and Australia, 98.9%-99.4% of
      Macroheterocera BINs exhibited the molecular synapomorphy of a phenylalanine in
      the 177th complete DNA barcode codon. Non-macroheteroceran BINs could thus be
      sifted out efficiently in the Malaise sample. The Madagascar micromoth fauna
      shows highest affinity with the Afrotropics (146 BINs also occur in the African
      continent). We found 22 recognised pests or invasive species, mostly occurring in
      disturbed habitats. Malaise trap samples show high temporal turnover and alpha
      diversity with as many as 507 BINs collected; of these, astonishingly, 499
      (98.4%) were novel to BOLD and 292 (57.6%) were singletons. Our results provide a
      baseline for future surveys across the island.

PMID- 30184445
TI  - Quality of Care in the United Kingdom after Removal of Financial Incentives.
AB  - BACKGROUND: The benefits of pay-for-performance schemes in improving the quality
      of care remain uncertain. There is little information on the effect of removing
      incentives from existing pay-for-performance schemes. METHODS: We conducted
      interrupted time-series analyses of electronic medical record (EMR) data from
      2010 to 2017 for 12 quality-of-care indicators in the United Kingdom's Quality
      and Outcomes Framework for which financial incentives were removed in 2014 and 6
      indicators for which incentives were maintained. We estimated the effects of
      removing incentives on changes in performance on quality-of-care measures.
      RESULTS: Complete longitudinal data were available for 2819 English primary care
      practices with more than 20 million registered patients. There were immediate
      reductions in documented quality of care for all 12 indicators in the first year
      after the removal of financial incentives. Reductions were greatest for
      indicators related to health advice, with a reduction of 62.3 percentage points
      (95% confidence interval [CI], -65.6 to -59.0) in EMR documentation of lifestyle
      counseling for patients with hypertension. Changes were smaller for indicators
      involving clinical actions that automatically update the EMR, such as laboratory
      testing, with a reduction of 10.7 percentage points (95% CI, -13.6 to -7.8) in
      control of cholesterol in patients with coronary heart disease and 12.1
      percentage points (95% CI, -13.6 to -10.6) for thyroid-function testing in
      patients with hypothyroidism. There was little change in performance on the 6
      quality measures for which incentives were maintained. CONCLUSIONS: Removal of
      financial incentives was associated with an immediate decline in performance on
      quality measures. In part, the decline probably reflected changes in EMR
      documentation, but declines on measures involving laboratory testing suggest that
      incentive removal also changed the care delivered.

PMID- 30184446
TI  - The Violence of Uncertainty - Undermining Immigrant and Refugee Health.

PMID- 30184447
TI  - Voluntary Euthanasia - Implications for Organ Donation.

PMID- 30184448
TI  - Peripheral Nerve Blocks for Hand Procedures.

PMID- 30184449
TI  - Black Hairy Tongue.

PMID- 30184450
TI  - High-Risk Clonal Hematopoiesis as the Origin of AITL and NPM1-Mutated AML.

PMID- 30184452
TI  - A Step Forward in the Treatment of Influenza.

PMID- 30184453
TI  - Just Beneath the Surface.

PMID- 30184454
TI  - E-Cigarettes, Incentives, and Drugs for Smoking Cessation.

PMID- 30184451
TI  - Rituximab plus Lenalidomide in Advanced Untreated Follicular Lymphoma.
AB  - BACKGROUND: Rituximab plus chemotherapy has been shown to be effective in
      patients with advanced-stage, previously untreated follicular lymphoma;
      nevertheless, most patients will have a relapse. Combination immunotherapy with
      lenalidomide and rituximab is an immunomodulatory regimen that has shown
      promising activity in patients with indolent B-cell non-Hodgkin's lymphoma.
      METHODS: We conducted this multicenter, international, phase 3 superiority trial
      to evaluate rituximab plus lenalidomide, as compared with rituximab plus
      chemotherapy, in patients with previously untreated follicular lymphoma. Patients
      were randomly assigned to receive one of the two regimens, followed by
      maintenance monotherapy with rituximab. Treatment with rituximab plus
      lenalidomide consisted of 18 cycles of the two drugs, followed by rituximab
      maintenance therapy every 8 weeks for 12 cycles (six additional doses). Treatment
      with rituximab plus chemotherapy consisted of the investigator's choice of one of
      three rituximab-based regimens, followed by maintenance monotherapy with
      rituximab every 8 weeks for 12 cycles. The primary end points were complete
      response (confirmed or unconfirmed) at 120 weeks and progression-free survival.
      RESULTS: A total of 1030 patients were randomly assigned to receive rituximab
      plus lenalidomide (513 patients) or rituximab plus chemotherapy (517 patients).
      The rate of confirmed or unconfirmed complete response at 120 weeks was similar
      in the two groups: 48% (95% confidence interval [CI], 44 to 53) in the rituximab
      lenalidomide group and 53% (95% CI, 49 to 57) in the rituximab-chemotherapy group
      (P=0.13). The interim 3-year rate of progression-free survival was 77% (95% CI,
      72 to 80) and 78% (95% CI, 74 to 82), respectively. A higher percentage of
      patients in the rituximab-chemotherapy group had grade 3 or 4 neutropenia (32%
      vs. 50%) and febrile neutropenia of any grade (2% vs. 7%), and a higher
      percentage of patients in the rituximab-lenalidomide group had grade 3 or 4
      cutaneous reactions (7% vs. 1%). CONCLUSIONS: Among patients with previously
      untreated follicular lymphoma, efficacy results were similar with rituximab plus
      lenalidomide and rituximab plus chemotherapy (with both regimens followed by
      rituximab maintenance therapy). The safety profile differed in the two groups.
      (Funded by Celgene; RELEVANCE ClinicalTrials.gov numbers, NCT01476787 and
      NCT01650701 , and EudraCT number, 2011-002792-42 .).

PMID- 30184456
TI  - Glandular Tularemia.

PMID- 30184457
TI  - Circulating Extracellular Vesicles in Human Disease.

PMID- 30184458
TI  - Incidence of Lung Cancer among Young Women.

PMID- 30184459
TI  - Rivaroxaban for Stroke Prevention after Embolic Stroke of Undetermined Source.

PMID- 30184460
TI  - Bezafibrate in Primary Biliary Cholangitis.

PMID- 30184461
TI  - Investigation of social, affective, and locomotor behavior of adolescent
      Brattleboro rats reveals a link between vasopressin's actions on arousal and
      social behavior.
AB  - Arginine vasopressin (AVP) has recently been implicated in juvenile and
      adolescent social development. How AVP influences social development, however, is
      not understood. Adolescent homozygous Brattleboro rats (Hom), which lack AVP due
      to a mutation in the Avp gene, exhibit fewer active social behaviors (e.g.,
      social play) but more passive social behaviors (e.g., huddling) than their wild
      type and heterozygous (Het) littermates, raising the possibility that AVP impacts
      social development through an arousal mechanism. Here, we test whether the
      atypical social phenotype of adolescent Hom rats is associated with altered
      behavioral arousal, social approach, or affective behaviors and whether
      Brattleboro mothers impact these behavioral phenotypes. Male and female Het and
      Hom adolescents born to Het or Hom mothers were tested in social interaction,
      open field, novelty-seeking, social approach, and marble burying tests. As
      reported previously, Hom rats played less and emitted fewer 50 kHz ultrasonic
      vocalizations while huddling more than their Het littermates. No genotype
      differences were detected in novelty seeking or social approach, nor were
      consistent differences found between offspring from Het and Hom mothers. However,
      Hom rats were less active in the open field and buried fewer marbles than Het
      rats indicating a hypoaroused, low anxiety phenotype. Open field activity
      correlated with levels of social play indicating that the effects of the
      Brattleboro mutation on arousal and social behavior are linked. These data
      demonstrate that chronic AVP deficiency impacts behavioral arousal during
      adolescence and support the hypothesis that AVP influences adolescent social
      development, in part, through its regulation of arousal.

PMID- 30184463
TI  - TGF-beta receptors: In and beyond TGF-beta signaling.
AB  - Transforming growth factor beta (TGF-beta) plays an important role in normal
      development and homeostasis. Dysregulation of TGF-beta responsiveness and its
      downstream signaling pathways contribute to many diseases, including cancer
      initiation, progression, and metastasis. TGF-beta ligands bind to three isoforms
      of the TGF-beta receptor (TGFBR) with different affinities. TGFBR1 and 2 are both
      serine/threonine and tyrosine kinases, but TGFBR3 does not have any kinase
      activity. They are necessary for activating canonical or noncanonical signaling
      pathways, as well as for regulating the activation of other signaling pathways.
      Another prominent feature of TGF-beta signaling is its context-dependent effects,
      temporally and spatially. The diverse effects and context dependency are either
      achieved by fine-tuning the downstream components or by regulating the
      expressions and activities of the ligands or receptors. Focusing on the receptors
      in events in and beyond TGF-beta signaling, we review the membrane trafficking of
      TGFBRs, the kinase activity of TGFBR1 and 2, the direct interactions between
      TGFBR2 and other receptors, and the novel roles of TGFBR3.

PMID- 30184462
TI  - Feedback-related neurophysiology in children and their parents: Developmental
      differences, familial transmission, and relationship to error-monitoring.
AB  - The feedback negativity (FN) and reward positivity (RewP) are event-related brain
      potentials (ERPs) that follow the presentation of negative and positive feedback
      information, respectively, and have become the focus of recent research on
      psychopathology because of their associations with symptom severity of and risk
      for depression. We advanced our understanding of these feedback-related ERPs by
      examining developmental differences, familial transmission, and associations with
      error-monitoring ERPs. Parents and their children completed parallel,
      developmentally-tailored guessing and go/no-go tasks while feedback- and error
      related ERPs were measured. We found that the Delta FN and RewP amplitudes
      increased with age and were larger in males than females among the child
      participants. The RewP also demonstrated familial transmission between fathers
      and their children. Finally, the FN and RewP were associated with error-related
      ERPs in children and adults, albeit in different ways. The current findings
      demonstrate that the FN and RewP have promise as developmentally-sensitive neural
      markers of reward and action monitoring processes associated with risk for
      psychopathology.

PMID- 30184455
TI  - Baloxavir Marboxil for Uncomplicated Influenza in Adults and Adolescents.
AB  - BACKGROUND: Baloxavir marboxil is a selective inhibitor of influenza cap
      dependent endonuclease. It has shown therapeutic activity in preclinical models
      of influenza A and B virus infections, including strains resistant to current
      antiviral agents. METHODS: We conducted two randomized, double-blind, controlled
      trials involving otherwise healthy outpatients with acute uncomplicated
      influenza. After a dose-ranging (10 to 40 mg) placebo-controlled trial, we
      undertook a placebo- and oseltamivir-controlled trial of single, weight-based
      doses of baloxavir (40 or 80 mg) in patients 12 to 64 years of age during the
      2016-2017 season. The dose of oseltamivir was 75 mg twice daily for 5 days. The
      primary efficacy end point was the time to alleviation of influenza symptoms in
      the intention-to-treat infected population. RESULTS: In the phase 2 trial, the
      median time to alleviation of influenza symptoms was 23.4 to 28.2 hours shorter
      in the baloxavir groups than in the placebo group (P<0.05). In the phase 3 trial,
      the intention-to-treat infected population included 1064 patients; 84.8 to 88.1%
      of patients in each group had influenza A(H3N2) infection. The median time to
      alleviation of symptoms was 53.7 hours (95% confidence interval [CI], 49.5 to
      58.5) with baloxavir, as compared with 80.2 hours (95% CI, 72.6 to 87.1) with
      placebo (P<0.001). The time to alleviation of symptoms was similar with baloxavir
      and oseltamivir. Baloxavir was associated with greater reductions in viral load 1
      day after initiation of the regimen than placebo or oseltamivir. Adverse events
      were reported in 20.7% of baloxavir recipients, 24.6% of placebo recipients, and
      24.8% of oseltamivir recipients. The emergence of polymerase acidic protein
      variants with I38T/M/F substitutions conferring reduced susceptibility to
      baloxavir occurred in 2.2% and 9.7% of baloxavir recipients in the phase 2 trial
      and phase 3 trial, respectively. CONCLUSIONS: Single-dose baloxavir was without
      evident safety concerns, was superior to placebo in alleviating influenza
      symptoms, and was superior to both oseltamivir and placebo in reducing the viral
      load 1 day after initiation of the trial regimen in patients with uncomplicated
      influenza. Evidence for the development of decreased susceptibility to baloxavir
      after treatment was also observed. (Funded by Shionogi; JapicCTI number, 153090,
      and CAPSTONE-1 ClinicalTrials.gov number, NCT02954354 .).

PMID- 30184465
TI  - Drug nanocrystallisation within liposomes.
AB  - Liposomes are phospholipid bilayer vesicles that have been explored in
      pharmaceutical research as drug delivery systems for >50 years. Despite being
      important to their morphology and drug release pattern, the physical state of the
      drug within liposomes (liquid, solid, crystalline form) is often overlooked. This
      review focuses on precipitation of drug within liposomes, which can result in the
      formation of confined nanocrystals, and consequent changes in liposome morphology
      and drug release patterns. The type of drugs that form nanocrystals within
      liposomes, preparation and characterisation of liposomal drug nanocrystals, and
      the in vitro drug release behaviour from these systems are communicated, with a
      discussion of their potential as drug delivery systems.

PMID- 30184464
TI  - Impact of a shift work-like lighting schedule on the functioning of the circadian
      system in the short-lived fish Nothobranchius furzeri.
AB  - Adult Nothobranchius furzeri of the MZM-04/10 strain were individually kept and
      subjected to a "5 + 2" shifting lighting schedule (SHIFT) for 8 weeks in order to
      evaluate the desynchronizing effects of a simulated human-like shift-work
      schedule on the functioning of the circadian system (CS). With this aim, sixteen
      21-week-old N. furzeri were placed into a Morning, Night and Evening schedule
      (lights on from 08:00 to 16:00, 00:00 to 08:00 and 16:00 to 00:00 h,
      respectively) and fed once a day in the middle of the corresponding photophase
      (12:00, 04:00 and 20:00 h, respectively). Then, in the weekends (2 days), fish
      were always returned to the Morning shift. As controls, 16 fish were maintained
      under a non-shifting LD cycle condition (CONTROL) throughout the whole
      experiment, with lights on from 08:00 to 16:00 h. Rest-activity rhythm (RAR) of
      fish subjected to SHIFT showed several symptoms of chronodisruption, such as a
      decrease in the percentage of diurnal activity and a reduction of the relative
      amplitude and the circadian function index with time. When a periodogram analysis
      was performed, RAR of N. furzeri under SHIFT conditions showed up to three
      separate circadian components: one longer than 24 h (26.5 h) that followed the
      weekly 8 h delays; a short-period component (~23 h) that was related to the
      weekend's phase advances, and finally, a 24 h component. The shifting LD schedule
      also affected fish CS at a molecular level, with several significant differences
      in the expression of core genes of the molecular clock (bmal1, clock, roralpha,
      rev-erbalpha) between SHIFT and CONTROL animals. RAR impairment along with
      changes in clock gene expression could be associated with high stress and
      accelerated aging in these fish.

PMID- 30184466
TI  - Cancer stem cells-emanated therapy resistance: Implications for liposomal drug
      delivery systems.
AB  - It is verified that failure in cancer therapy by conventional chemotherapeutic
      agents arise from cancer heterogeneity. That, a small subpopulation of cancer
      cells known as "cancer stem cells" (CSCs) are shown to be responsible for
      deriving clonal heterogeneity/diversity in tumors, which render them resistant to
      conventional treatment regimes. So far, efficient targeted cancer therapy by
      nanotechnology-based drug delivery approaches is well established. Among various
      introduced nanocarriers, the non-toxic nature and biocompatibility of liposome
      make it highly desirable for human studies. In addition, liposomal nanocarriers
      can be used to protect entrapped therapeutic agents against chemical and
      biological degradation, improve solubility of the encapsulated drugs, provide
      sustained drug release, extend in vivo half-life, reduce side effects, improve
      drug pharmacokinetic and pharmacodynamic profiles, reduce drug dosage and
      administration frequency. Further, multifunctional liposomes can be envisioned
      that are simultaneously loaded with different theranostics and chemically
      modified with different tumor-specific surface ligands for targeted therapy. Such
      versatile nanocarrier can influence the physicochemical characteristics,
      immunological mechanisms, and uptake mechanisms following systemic delivery.
      Other strategies to improve tumor-specific tropism include delivery systems
      involving immune cells or their modulators. Here, we describe mechanisms by which
      CSC can promote drug resistance to impair the efficacy of cancer therapies. Then,
      we summarize the implication of each of these mechanisms as potential
      therapeutics ways to overcome the therapeutically-resistant CSCs. Further, we
      discuss the status, therapeutic potential and prospect of different liposomal
      drug delivery systems in overcoming CSC drug resistance in the clinic.

PMID- 30184467
TI  - Inhibition of return (IOR) in patients with schizophrenia and cannabis use.
AB  - Research concerning the spatial orientation in patients with schizophrenia has
      demonstrated a state independent deficit in inhibition of return (IOR), which has
      been discussed as a vulnerability marker for schizophrenia. Other recent
      investigations on brain structure and cognitive processing have revealed less
      deficits in schizophrenia patients with comorbid cannabis use (SCH + CUD)
      compared to abstinent schizophrenia patients (SCH). It was hypothesized that
      these results may reflect a premorbid lower vulnerability in at least a subgroup
      of comorbid patients. The aim of the present study is to extend previous work by
      investigating IOR functioning in patients with schizophrenia and cannabis use.
      This in turn should supplement the existing studies on the vulnerability of this
      patient group. Therefore, we compared IOR functioning in four groups: 62 patients
      with schizophrenia and 46 healthy controls, both with and without cannabis use.
      Participants underwent a covert orienting of attention task (COVAT) with
      peripheral cues and three stimulus onset asynchronies (SOAs: 200 ms, 400 ms and
      800 ms). Both schizophrenia groups displayed delayed IOR with a more pronounced
      IOR effect in SCH + CUD compared to SCH. In healthy controls, IOR did not seem to
      be significantly affected by cannabis use. Significant IOR-differences between
      groups were only seen between SCH patients without cannabis use and both healthy
      groups at SOA 400 ms. Patterns of cannabis use as well as clinical parameters of
      psychoses did not affect IOR. Our results may support the hypothesis of IOR as a
      vulnerability marker for schizophrenia and of a lower biological vulnerability in
      at least a subgroup of SCH + CUD.

PMID- 30184468
TI  - Dynamics of tRNA dissociation in early and later cycles of translation elongation
      by the ribosome.
AB  - Deacylated tRNA dissociation from E site and aminoacyl-tRNA binding to the A site
      of the ribosome play a critical role in repetitive cycles of protein synthesis.
      Available experimental data showed that in the small range of aminoacyl-tRNA
      concentrations, during the first few cycles of translation elongation (initiation
      phase of translation) the E-site tRNA can be dissociated either before or after
      the A-site tRNA binding, while during the later cycles of elongation (elongation
      phase) the E-site tRNA is mostly dissociated before the A-site tRNA binding.
      Here, based on our proposed model of translation elongation we study analytically
      the dynamics of the E-site tRNA dissociation and A-site tRNA binding, providing
      quantitative explanations of the available experimental data in both the
      initiation and elongation phases. In our model there exist two routes of state
      transitions within an elongation cycle in the initiation phase, with each route
      having stochastic E-site tRNA dissociation but with different dissociation rates.
      Thus, the E-site tRNA dissociation is governed by a stochastic competition
      between the tRNA dissociation and A-site tRNA association reactions, although in
      the small range of aminoacyl-tRNA concentrations used in the experiments it seems
      that such stochastic competition does not exist. Moreover, the detailed
      comparisons between the dynamics of tRNA dissociation in the initiation phase and
      that in the elongation phase are made.

PMID- 30184469
TI  - Lysosomal dysfunction and early glial activation are involved in the pathogenesis
      of spinocerebellar ataxia type 21 caused by mutant transmembrane protein 240.
AB  - Spinocerebellar ataxia type 21 (SCA21) is caused by missense or nonsense
      mutations of the transmembrane protein 240 (TMEM240). Molecular mechanisms of
      SCA21 pathogenesis remain unknown because the functions of TMEM240 have not been
      elucidated. We aimed to reveal the molecular pathogenesis of SCA21 using cell and
      mouse models that overexpressed the wild-type and SCA21 mutant TMEM240. In HeLa
      cells, overexpressed TMEM240 localized around large cytoplasmic vesicles. The
      SCA21 mutation did not affect this localization. Because these vesicles contained
      endosomal markers, we evaluated the effect of TMEM240 fused with a FLAG tag (TMEM
      FL) on endocytosis and autophagic protein degradation. Wild-type TMEM-FL
      significantly impaired clathrin-mediated endocytosis, whereas the SCA21 mutants
      did not. The SCA21 mutant TMEM-FL significantly impaired autophagic lysosomal
      protein degradation, in contrast to wild-type. Next, we investigated how TMEM240
      affects the neural morphology of primary cultured cerebellar Purkinje cells
      (PCs). The SCA21 mutant TMEM-FL significantly prevented the dendritic development
      of PCs, in contrast to the wild-type. Finally, we assessed mice that expressed
      wild-type or SCA21 mutant TMEM-FL in cerebellar neurons using adeno-associated
      viral vectors. Mice expressing the SCA21 mutant TMEM-FL showed impaired motor
      coordination. Although the SCA21 mutant TMEM-FL did not trigger
      neurodegeneration, activation of microglia and astrocytes was induced before
      motor miscoordination. In addition, immunoblot experiments revealed that
      autophagic lysosomal protein degradation, especially chaperone-mediated
      autophagy, was also impaired in the cerebella that expressed the SCA21 mutant
      TMEM-FL. These dysregulated functions in vitro, and induction of early gliosis
      and lysosomal impairment in vivo by the SCA21 mutant TMEM240 may contribute to
      the pathogenesis of SCA21.

PMID- 30184470
TI  - Hypodermin C improves the survival of kidney allografts.
AB  - Although immunosuppressive therapies have made organ transplantation a common
      medical procedure worldwide, chronic toxicity is a major issue of long-term
      treatment. One method to improve such therapies is the application of
      immunomodulatory agents from parasites, such as Hypoderma lineatum (Diptera:
      Oestridae). Hypodermin C (HC) is an enzyme secreted by H. lineatum larvae, and
      our previous study showed that recombinant HC could degrade guinea pig C3 and
      inhibit the complement pathway in vitro, suggesting potential activity for
      inhibiting transplant rejection. However, such properties have not been fully
      demonstrated in vivo. In this study, we investigated the impact of HC on a fully
      MHC-mismatched, life-sustaining, murine model of kidney allograft rejection using
      B6 donors and BABL/c (HC transgenic or wild-type) recipients. Kidney grafts were
      analyzed by histology, immunohistochemistry and western blotting. The results
      suggested that HC could effectively inhibit kidney allograft rejection. These
      findings suggest HC is a promising strategy to improve the survival of human
      implants.

PMID- 30184471
TI  - Ginsenoside Rb1 protects against spinal cord ischemia-reperfusion injury in rats
      by downregulating the Bax/Bcl-2 ratio and caspase-3 and p-Ask-1 levels.
AB  - The aim of this study was to confirm the effects of ginsenoside Rb1 on neural
      cell apoptosis in the spinal cord of rats with spinal cord ischemia-reperfusion
      injury (SCII) and to explore its potential mechanisms. A total of 100 healthy
      adult Sprague-Dawley (SD) rats were randomly divided into four groups: normal
      control (n = 10), sham-operated (n = 10), SCII model (n = 40), and ginsenoside
      Rb1-treated groups (n = 40). Basso, Beattie, Bresnahan (BBB) scale was used to
      examine rat hindlimb locomotor function. Nissl and Tunnel staining were used to
      observe neural cell injury and apoptosis, respectively, in the spinal cord of
      rats with SCII. Immunofluorescence staining was performed to detect the
      expression of Bax and Bcl-2. The levels of caspase-3 and phosphorylated Ask-1 (p
      Ask-1) were detected by western blotting. Ginsenoside Rb1 prevented neural cell
      apoptosis in the spinal cord and improved hindlimb locomotor dysfunction of rats
      (P < .05). Moreover, SCII-induced upregulation of caspase-3 and p-Ask-1 levels
      and the Bax/Bcl-2 ratio were significantly decreased by ginsenoside Rb1 (P <
      .05). The protective effects of ginsenoside Rb1 on neural cells in the spinal
      cord of rats with SCII were mediated by the ginsenoside Rb1-induced
      downregulation of caspase-3 and p-Ask-1 levels and the Bax/Bcl-2 ratio.

PMID- 30184472
TI  - Novel symmetry-based gene-gene dissimilarity measures utilizing Gene Ontology:
      Application in gene clustering.
AB  - In recent years DNA microarray technology, leading to the generation of high
      volume biological data, has gained significant attention. To analyze this high
      volume gene-expression data, one such powerful tool is Clustering. For any
      clustering algorithm, its efficiency majorly depends upon the underlying
      similarity/dissimilarity measure. During the analysis of such data often there is
      a need to further explore the similarity of genes not only with respect to their
      expression values but also with respect to their functional annotations, which
      can be obtained from Gene Ontology (GO) databases. In the existing literature,
      several novel clustering and bi-clustering approaches were proposed to identify
      co-regulated genes from gene-expression datasets. Identifying co-regulated genes
      from gene expression data misses some important biological information about
      functionalities of genes, which is necessary to identify semantically related
      genes. In this paper, we have proposed sixteen different semantic gene-gene
      dissimilarity measures utilizing biological information of genes retrieved from a
      global biological database namely Gene Ontology (GO). Four proximity measures,
      viz. Euclidean, Cosine, point symmetry and line symmetry are utilized along with
      four different representations of gene-GO-term annotation vectors to develop
      total sixteen gene-gene dissimilarity measures. In order to illustrate the
      profitability of developed dissimilarity measures, some multi-objective as well
      as single-objective clustering algorithms are applied utilizing proposed measures
      to identify functionally similar genes from Mouse genome and Yeast datasets.
      Furthermore, we have compared the performance of our proposed sixteen
      dissimilarity measures with three existing state-of-the-art semantic similarity
      and distance measures.

PMID- 30184473
TI  - A kernel machine method for detecting higher order interactions in multimodal
      datasets: Application to schizophrenia.
AB  - BACKGROUND: Technological advances are enabling us to collect multimodal datasets
      at an increasing depth and resolution while with decreasing labors. Understanding
      complex interactions among multimodal datasets, however, is challenging. NEW
      METHOD: In this study, we tested the interaction effect of multimodal datasets
      using a novel method called the kernel machine for detecting higher order
      interactions among biologically relevant multimodal data. Using a semiparametric
      method on a reproducing kernel Hilbert space, we formulated the proposed method
      as a standard mixed-effects linear model and derived a score-based variance
      component statistic to test higher order interactions between multimodal
      datasets. RESULTS: The method was evaluated using extensive numerical simulation
      and real data from the Mind Clinical Imaging Consortium with both schizophrenia
      patients and healthy controls. Our method identified 13-triplets that included 6
      gene-derived SNPs, 10 ROIs, and 6 gene-specific DNA methylations that are
      correlated with the changes in hippocampal volume, suggesting that these triplets
      may be important for explaining schizophrenia-related neurodegeneration.
      COMPARISON WITH EXISTING METHOD(S): The performance of the proposed method is
      compared with the following methods: test based on only first and first few
      principal components followed by multiple regression, and full principal
      component analysis regression, and the sequence kernel association test.
      CONCLUSIONS: With strong evidence (p-value <=0.000001), the triplet (MAGI2,
      CRBLCrus1.L, FBXO28) is a significant biomarker for schizophrenia patients. This
      novel method can be applicable to the study of other disease processes, where
      multimodal data analysis is a common task.

PMID- 30184474
TI  - Environmental exposure to perchlorate: A review of toxicology and human health.
AB  - Perchlorate pharmacology and toxicology studies date back at least 65 years in
      the peer-reviewed literature. Repeated studies in animals and humans have
      demonstrated perchlorate's mechanism of action, dose-response, and adverse
      effects over a range of doses. The first measurable effect of perchlorate is
      inhibition of iodine uptake to the thyroid gland. Adequate levels of thyroid
      hormones are critical for the development of the fetal nervous system. With
      sufficient dose and exposure duration, perchlorate can reduce thyroid hormones in
      the pregnant or non-pregnant woman via this mechanism. The developing fetus is
      the most sensitive life stage for chemical agents that affect iodide uptake to
      the thyroid. Perchlorate has a half-life of eight hours, is not metabolized, does
      not bioaccumulate, is not a mutagen or carcinogen, and is not reprotoxic or
      immunotoxic. More recently, epidemiological and biomonitoring studies have been
      published in the peer-reviewed literature characterizing the thyroidal effects of
      perchlorate and other goitrogens. While the results from most populations report
      no consistent association, a few studies report thyroidal effects at
      environmentally relevant levels of perchlorate. We reviewed the literature on
      health effects of perchlorate at environmental exposure levels, with a focus on
      exposures during pregnancy and neurodevelopmental effects. Based on the studies
      we reviewed, health effects are expected to only occur at doses substantially
      higher than environmental levels.

PMID- 30184475
TI  - Activity of ecto-5'-nucleotidase (NT5E/CD73) is increased in papillary thyroid
      carcinoma and its expression is associated with metastatic lymph nodes.
AB  - The incidence of papillary thyroid carcinoma (PTC) has been increasing, which
      raised the interest in its molecular pathways. Although the high expression of
      ecto-5'-nucleotidase (NT5E) gene expression and NT5E enzymatic activity in
      several types of cancer is associated with tumor progression, its role in PTC
      remains unknown. Here, we investigated the AMP hydrolysis in human normal thyroid
      cells and PTC cells, in primary culture, and the association of NT5E expression
      with clinical aspects of PTC patients. AMPase activity was higher in thyroid
      cells isolated from PTC, as compared to normal thyroid (P = 0.0063). Significant
      correlation was observed between AMPase activity and NT5E levels in primary
      thyroid cell cultures (r = 0.655, P = 0.029). NT5E expression was higher in PTC
      than in the adjacent non-malignant thyroid tissue (P = 0.0065) and were
      positively associated with metastatic lymph nodes (P = 0.0007), risk of
      recurrence (P = 0.0033), tumor size (P = 0.049), and nodular hyperplasia in the
      adjacent thyroid parenchyma, when compared to normal thyroid or lymphocytic
      thyroiditis (P = 0.0146). After adjusting for potential confounders, the
      malignant/non-malignant paired expression ratio of NT5E mRNA was independently
      associated with metastatic lymph nodes (P = 0.0005), and tumor size (P=0.0005).
      In addition, the analysis of PTC described in the TCGA database also showed an
      association between higher expression of NT5E and metastatic lymph nodes, and
      tumor microinvasion. These results support the hypothesis that NT5E have a role
      in PTC microenvironment and might be a potential target for PTC therapy.

PMID- 30184476
TI  - Recapitulating kidney development: Progress and challenges.
AB  - Decades of research into the molecular and cellular regulation of kidney
      morphogenesis in rodent models, particularly the mouse, has provided both an
      atlas of the mammalian kidney and a roadmap for recreating kidney cell types with
      potential applications for the treatment of kidney disease. With advances in both
      our capacity to maintain nephron progenitors in culture, reprogram to kidney cell
      types and direct the differentiation of human pluripotent stem cells to kidney
      endpoints, renal regeneration via cellular therapy or tissue engineering may be
      possible. Human kidney models also have potential for disease modelling and drug
      screening. Such applications will rely upon the accuracy of the model at the
      cellular level and the capacity for stem-cell derived kidney tissue to
      recapitulate both normal and diseased kidney tissue. In this review, we will
      discuss the available cell sources, how well they model the human kidney and how
      far we are from application either as models or for tissue engineering.

PMID- 30184477
TI  - Cytokine targets in lupus nephritis: Current and future prospects.
AB  - Despite advancements in the care of lupus nephritis, a considerable proportion of
      patients may respond poorly or flare while on conventional immunosuppressive
      agents. Studies in murine and human lupus have illustrated a pathogenic role for
      several cytokines by enhancing T- and B-cell activation, autoantibodies
      production and affecting the function of kidney resident cells, therefore
      supporting their potential therapeutic targeting. To this end, there is limited
      post-hoc randomized evidence to suggest beneficial effect of belimumab,
      administered on top of standard-of-care, during maintenance therapy in lupus
      nephritis. Type I interferon receptor blockade has yielded promising results in
      preliminary SLE trials yet data on renal activity are unavailable. Conversely,
      targeting interleukin-6 and interferon-gamma both failed to demonstrate a
      significant renal effect. For several other targets, preclinical data are
      encouraging but will require confirmation. We envision that high-throughput
      technologies will enable accurate patient stratification, thus offering the
      opportunity for personalized implementation of cytokine-targeting therapies.

PMID- 30184478
TI  - Extending the Code of Sequence Readout by Gene Regulatory Proteins: The Role of
      Hoogsteen Base Pairing in p53-DNA Recognition.
AB  - The tumor suppressor p53 regulates the transcription of a myriad of target genes.
      In this issue of Structure, Golovenko et al. (2018) elucidate the role of non
      canonical Hoogsteen A/T base pairs in p53-DNA recognition, highlighting DNA shape
      as an additional layer of sequence readout.

PMID- 30184479
TI  - Selecting New RNA Crystal Contacts.
AB  - RNAs are relatively difficult to crystallize because many sequence variants must
      be tested to obtain suitable crystal contacts. In this issue of Structure,
      Shoffner et al. (2018) report an in crystallo selection procedure that allows for
      the rapid generation of new RNA crystal contacts.

PMID- 30184480
TI  - Dispelling a Few Cell Metabolism Misconceptions.

PMID- 30184481
TI  - A Mitochondrial-Derived Peptide Exercises the Nuclear Option.
AB  - The vast majority of mitochondrial proteins are encoded by nuclear genes, giving
      the nucleus ultimate control of mitochondrial biogenesis, dynamics, and function.
      However, in this issue Kim et al. (2018) demonstrate a reversal of fortune,
      whereby an mtDNA-encoded peptide, MOTS-c, is targeted to the nucleus to signal
      changes in gene expression.

PMID- 30184482
TI  - T Cell Metabolism Has Evolved to Tolerate Tuberculosis.
AB  - Although T cells are important in preventing tuberculosis progression, their role
      in disease tolerance is unknown. Recently in Science Immunology, Tzelepis et al.
      (2018) have revealed that mitochondrial cyclophilin D controls T cell metabolism
      and proliferation, contributing to tolerance. Cyclophilin D loss leads to
      immunopathology and increased mortality, without impacting bacterial burden.

PMID- 30184483
TI  - Metformin: An Old Dog with a New Trick?
AB  - Idiopathic pulmonary fibrosis (IPF) remains an important medical challenge, but
      recent translational data have provided clues implicating deficient AMPK
      signaling in persistently activated myelofibroblasts within fibrotic foci. A new
      study in Nature Medicine reports that pharmacological activation of AMPK with
      metformin can reverse established fibrosis by facilitating deactivation and
      apoptosis of myofibroblasts.

PMID- 30184484
TI  - The Role of Advanced Glycation End Products in Aging and Metabolic Diseases:
      Bridging Association and Causality.
AB  - Accumulation of advanced glycation end products (AGEs) on nucleotides, lipids,
      and peptides/proteins are an inevitable component of the aging process in all
      eukaryotic organisms, including humans. To date, a substantial body of evidence
      shows that AGEs and their functionally compromised adducts are linked to and
      perhaps responsible for changes seen during aging and for the development of many
      age-related morbidities. However, much remains to be learned about the biology of
      AGE formation, causal nature of these associations, and whether new interventions
      might be developed that will prevent or reduce the negative impact of AGEs
      related damage. To facilitate achieving these latter ends, we show how
      invertebrate models, notably Drosophila melanogaster and Caenorhabditis elegans,
      can be used to explore AGE-related pathways in depth and to identify and assess
      drugs that will mitigate against the detrimental effects of AGE-adduct
      development.

PMID- 30184485
TI  - The MIC-1/GDF15-GFRAL Pathway in Energy Homeostasis: Implications for Obesity,
      Cachexia, and Other Associated Diseases.
AB  - MIC-1/GDF15 is a stress response cytokine and a distant member of the
      transforming growth factor beta (TGFb) superfamily, with no close relatives. It
      acts via a recently identified receptor called glial-derived neurotrophic factor
      (GDNF) receptor alpha-like (GFRAL), which is a distant orphan member of the GDNF
      receptor family that signals through the tyrosine kinase receptor Ret. MIC
      1/GDF15 expression and serum levels rise in response to many stimuli that
      initiate cell stress and as part of a wide variety of disease processes, most
      prominently cancer and cardiovascular disease. The best documented actions of MIC
      1/GDF15 are on regulation of energy homeostasis. When MIC-1/GDF15 serum levels
      are substantially elevated in diseases like cancer, it subverts a physiological
      pathway of appetite regulation to induce an anorexia/cachexia syndrome initiated
      by its actions on hindbrain neurons. These effects make it a potential target for
      the treatment of both obesity and anorexia/cachexia syndromes, disorders lacking
      any highly effective, readily accessible therapies.

PMID- 30184486
TI  - Glycolytic Stimulation Is Not a Requirement for M2 Macrophage Differentiation.
AB  - Enhanced glucose uptake and a switch to glycolysis are key traits of M1
      macrophages, whereas enhanced fatty acid oxidation and oxidative phosphorylation
      are the main metabolic characteristics of M2 macrophages. Recent studies
      challenge this traditional view, indicating that glycolysis may also be
      critically important for M2 macrophage differentiation, based on experiments with
      2-DG. Here we confirm the inhibitory effect of 2-DG on glycolysis, but also
      demonstrate that 2-DG impairs oxidative phosphorylation and significantly reduces
      13C-labeled Krebs cycle metabolites and intracellular ATP levels. These metabolic
      derangements were associated with reduced JAK-STAT6 pathway activity and M2
      differentiation marker expression. While glucose deprivation and glucose
      substitution with galactose effectively suppressed glycolytic activity, there was
      no effective suppression of oxidative phosphorylation, intracellular ATP levels,
      STAT6 phosphorylation, and M2 differentiation marker expression. These data
      indicate that glycolytic stimulation is not required for M2 macrophage
      differentiation as long as oxidative phosphorylation remains active.

PMID- 30184487
TI  - The Impact of Visual Cues, Reward, and Motor Feedback on the Representation of
      Behaviorally Relevant Spatial Locations in Primary Visual Cortex.
AB  - The integration of visual stimuli and motor feedback is critical for successful
      visually guided navigation. These signals have been shown to shape neuronal
      activity in the primary visual cortex (V1), in an experience-dependent manner.
      Here, we examined whether visual, reward, and self-motion-related inputs are
      integrated in order to encode behaviorally relevant locations in V1 neurons.
      Using a behavioral task in a virtual environment, we monitored layer 2/3 neuronal
      activity as mice learned to locate a reward along a linear corridor. With
      learning, a subset of neurons became responsive to the expected reward location.
      Without a visual cue to the reward location, both behavioral and neuronal
      responses relied on self-motion-derived estimations. However, when visual cues
      were available, both neuronal and behavioral responses were driven by visual
      information. Therefore, a population of V1 neurons encode behaviorally relevant
      spatial locations, based on either visual cues or on self-motion feedback when
      visual cues are absent.

PMID- 30184488
TI  - RanBP1 Couples Nuclear Export and Golgi Regulation through LKB1 to Promote
      Cortical Neuron Polarity.
AB  - Neuronal polarity in the developing cortex begins during the early stages of
      neural progenitor migration toward the cortical plate and culminates with the
      specification of the axon and dendrites. Here, we demonstrate that the Ran
      dependent nucleocytoplasmic transport machinery is essential for the
      establishment of cortical neuron polarity. We found that Ran-binding protein 1
      (RanBP1) regulates axon specification and dendritic arborization in cultured
      neurons in vitro and radial neural migration in vivo. During axonogenesis, RanBP1
      regulates the cytoplasmic levels of the polarity protein LKB1/Par4, and this is
      dependent on the nuclear export machinery. Our results show that downstream of
      RanBP1, LKB1 function is mediated by the STK25-GM130 pathway, which promotes
      axonogenesis through Golgi regulation. Our results indicate that the
      nucleocytoplasmic transport machinery is a main regulator of neuron polarity,
      including radial migration, and that the regulated export of LKB1 through RanBP1
      is a limiting step of axonogenesis.

PMID- 30184489
TI  - Lin28 Signaling Supports Mammalian PNS and CNS Axon Regeneration.
AB  - RNA-binding proteins Lin28a/b regulate cellular growth and tissue regeneration.
      Here, we investigated the role of Lin28 in the control of axon regeneration in
      postmitotic neurons. We find that Lin28a/b are both necessary and sufficient for
      supporting axon regeneration in mature sensory neurons through their regulatory
      partners, let-7 microRNAs (miRNAs). More importantly, overexpression of Lin28a in
      mature retinal ganglion cells (RGCs) produces robust and sustained optic nerve
      regeneration. Additionally, combined overexpression of Lin28a and downregulation
      of Pten in RGCs act additively to promote optic nerve regeneration, potentially
      by reducing the backward turning of regenerating RGC axons. Our findings not only
      reveal a vital role of Lin28 signaling in regulating mammalian axon regeneration
      but also identify a signaling pathway that can promote axon regeneration in the
      central nervous system (CNS).

PMID- 30184491
TI  - Macrophages Regulate Schwann Cell Maturation after Nerve Injury.
AB  - Pro-regenerative macrophages are well known for their role in promoting tissue
      repair; however, their specific roles in promoting regeneration of the injured
      nerve are not well defined. Specifically, how macrophages interact with Schwann
      cells following injury during remyelination has been largely unexplored. We
      demonstrate that after injury, including in humans, macrophages function to clear
      debris and persist within the nerve microenvironment. Macrophage ablation
      immediately preceding remyelination results in an increase in immature Schwann
      cell density, a reduction in remyelination, and long-term deficits in conduction
      velocity. Targeted RNA-seq of macrophages from injured nerve identified Gas6 as
      one of several candidate factors involved in regulating Schwann cell dynamics.
      Functional studies show that the absence of Gas6 within monocyte lineage cells
      impairs Schwann cell remyelination within the injured nerve. These results
      demonstrate a role for macrophages in regulating Schwann cell function during
      nerve regeneration and highlight a molecular mechanism by which this occurs.

PMID- 30184490
TI  - Nuclear Localization of Huntingtin mRNA Is Specific to Cells of Neuronal Origin.
AB  - Huntington's disease (HD) is a monogenic neurodegenerative disorder representing
      an ideal candidate for gene silencing with oligonucleotide therapeutics (i.e.,
      antisense oligonucleotides [ASOs] and small interfering RNAs [siRNAs]). Using an
      ultra-sensitive branched fluorescence in situ hybridization (FISH) method, we
      show that ~50% of wild-type HTT mRNA localizes to the nucleus and that its
      nuclear localization is observed only in neuronal cells. In mouse brain sections,
      we detect Htt mRNA predominantly in neurons, with a wide range of Htt foci
      observed per cell. We further show that siRNAs and ASOs efficiently eliminate
      cytoplasmic HTT mRNA and HTT protein, but only ASOs induce a partial but
      significant reduction of nuclear HTT mRNA. We speculate that, like other mRNAs,
      HTT mRNA subcellular localization might play a role in important neuronal
      regulatory mechanisms.

PMID- 30184492
TI  - A Chimeric Lloviu Virus Minigenome System Reveals that the Bat-Derived Filovirus
      Replicates More Similarly to Ebolaviruses than Marburgviruses.
AB  - Recently, traces of zoonotic viruses have been discovered in bats and other
      species around the world, but despite repeated attempts, full viral genomes have
      not been rescued. The absence of critical genetic sequences from these viruses
      and the difficulties to isolate infectious virus from specimens prevent research
      on their pathogenic potential for humans. One example of these zoonotic pathogens
      is Lloviu virus (LLOV), a filovirus that is closely related to Ebola virus. Here,
      we established LLOV minigenome systems based on sequence complementation from
      other filoviruses. Our results show that the LLOV replication and transcription
      mechanisms are, in general, more similar to ebolaviruses than to marburgviruses.
      We also show that a single nucleotide at the 3' genome end determines species
      specificity of the LLOV polymerase. The data obtained here will be instrumental
      for the rescue of infectious LLOV clones for pathogenesis studies.

PMID- 30184493
TI  - Differential Splicing of ANP32A in Birds Alters Its Ability to Stimulate RNA
      Synthesis by Restricted Influenza Polymerase.
AB  - Adaptation of viruses to their hosts can result in specialization and a
      restricted host range. Species-specific polymorphisms in the influenza virus
      polymerase restrict its host range during transmission from birds to mammals.
      ANP32A was recently identified as a cellular co-factor affecting polymerase
      adaption and activity. Avian influenza polymerases require ANP32A containing an
      insertion resulting from an exon duplication uniquely encoded in birds. Here we
      find that natural splice variants surrounding this exon create avian ANP32A
      proteins with distinct effects on polymerase activity. We demonstrate species
      independent direct interactions between all ANP32A variants and the PB2
      polymerase subunit. This interaction is enhanced in the presence of viral genomic
      RNA. In contrast, only avian ANP32A restored ribonucleoprotein complex assembly
      for a restricted polymerase by enhancing RNA synthesis. Our data suggest that
      ANP32A splicing variation among birds differentially affects viral replication,
      polymerase adaption, and the potential of avian hosts to be reservoirs.

PMID- 30184494
TI  - Mitochondrial Trafficking and Processing of Telomerase RNA TERC.
AB  - Mitochondrial dysfunctions play major roles in many diseases. However, how
      mitochondrial stresses are relayed to downstream responses remains unclear. Here
      we show that the RNA component of mammalian telomerase TERC is imported into
      mitochondria, processed to a shorter form TERC-53, and then exported back to the
      cytosol. We found that the import is regulated by PNPASE, and the processing is
      controlled by mitochondrion-localized RNASET2. Cytosolic TERC-53 levels respond
      to changes in mitochondrial functions but have no direct effect on these
      functions. These findings uncover a mitochondrial RNA trafficking pathway and
      provide a potential mechanism for mitochondria to relay their functional states
      to other cellular compartments.

PMID- 30184495
TI  - Triglycerides Promote Lipid Homeostasis during Hypoxic Stress by Balancing Fatty
      Acid Saturation.
AB  - Lipid droplets, which store triglycerides and cholesterol esters, are a prominent
      feature of clear cell renal cell carcinoma (ccRCC). Although their presence in
      ccRCC is critical for sustained tumorigenesis, their contribution to lipid
      homeostasis and tumor cell viability is incompletely understood. Here we show
      that disrupting triglyceride synthesis compromises the growth of both ccRCC
      tumors and ccRCC cells exposed to tumor-like conditions. Functionally, hypoxia
      leads to increased fatty acid saturation through inhibition of the oxygen
      dependent stearoyl-CoA desaturase (SCD) enzyme. Triglycerides counter a toxic
      buildup of saturated lipids, primarily by releasing the unsaturated fatty acid
      oleate (the principal product of SCD activity) from lipid droplets into
      phospholipid pools. Disrupting this process derails lipid homeostasis, causing
      overproduction of toxic saturated ceramides and acyl-carnitines as well as
      activation of the NF-kappaB transcription factor. Our work demonstrates that
      triglycerides promote homeostasis by "buffering" specific fatty acids.

PMID- 30184496
TI  - Asymmetrically Positioned Flagellar Control Units Regulate Human Sperm Rotation.
AB  - Ion channels control sperm navigation within the female reproductive tract and,
      thus, are critical for their ability to find and fertilize an egg. The flagellar
      calcium channel CatSper controls sperm hyperactivated motility and is dependent
      on an alkaline cytoplasmic pH. The latter is accomplished by either proton
      transporters or, in human sperm, via the voltage-gated proton channel Hv1. To
      provide concerted regulation, ion channels and their regulatory proteins must be
      compartmentalized. Here, we describe flagellar regulatory nanodomains comprised
      of Hv1, CatSper, and its regulatory protein ABHD2. Super-resolution microscopy
      revealed that Hv1 is distributed asymmetrically within bilateral longitudinal
      lines and that inhibition of this channel leads to a decrease in sperm rotation
      along the long axis. We suggest that specific distribution of flagellar
      nanodomains provides a structural basis for the selective activation of CatSper
      and subsequent flagellar rotation. The latter, together with hyperactivated
      motility, enhances the fertility of sperm.

PMID- 30184497
TI  - Asymmetric Processing of DNA Ends at a Double-Strand Break Leads to Unconstrained
      Dynamics and Ectopic Translocation.
AB  - Multiple pathways regulate the repair of double-strand breaks (DSBs) to suppress
      potentially dangerous ectopic recombination. Both sequence and chromatin context
      are thought to influence pathway choice between non-homologous end-joining (NHEJ)
      and homology-driven recombination. To test the effect of repetitive sequences on
      break processing, we have inserted TG-rich repeats on one side of an inducible
      DSB at the budding yeast MAT locus on chromosome III. Five clustered Rap1 sites
      within a break-proximal TG repeat are sufficient to block Mre11-Rad50-Xrs2
      recruitment, impair resection, and favor elongation by telomerase. The two sides
      of the break lose end-to-end tethering and show enhanced, uncoordinated movement.
      Only the TG-free side is resected and shifts to the nuclear periphery. In
      contrast to persistent DSBs without TG repeats that are repaired by imprecise
      NHEJ, nearly all survivors of repeat-proximal DSBs repair the break by a homology
      driven, non-reciprocal translocation from ChrIII-R to ChrVII-L. This suppression
      of imprecise NHEJ at TG-repeat-flanked DSBs requires the Uls1 translocase
      activity.

PMID- 30184499
TI  - PRMT5 Regulates DNA Repair by Controlling the Alternative Splicing of Histone
      Modifying Enzymes.
AB  - Protein arginine methyltransferase 5 (PRMT5) is overexpressed in many cancer
      types and is a promising therapeutic target for several of them, including
      leukemia and lymphoma. However, we and others have reported that PRMT5 is
      essential for normal physiology. This dependence may become dose limiting in a
      therapeutic setting, warranting the search for combinatorial approaches. Here, we
      report that PRMT5 depletion or inhibition impairs homologous recombination (HR)
      DNA repair, leading to DNA-damage accumulation, p53 activation, cell-cycle
      arrest, and cell death. PRMT5 symmetrically dimethylates histone and non-histone
      substrates, including several components of the RNA splicing machinery. We find
      that PRMT5 depletion or inhibition induces aberrant splicing of the
      multifunctional histone-modifying and DNA-repair factor TIP60/KAT5, which
      selectively affects its lysine acetyltransferase activity and leads to impaired
      HR. As HR deficiency sensitizes cells to PARP inhibitors, we demonstrate here
      that PRMT5 and PARP inhibitors have synergistic effects on acute myeloid leukemia
      cells.

PMID- 30184498
TI  - ATR-Mediated Global Fork Slowing and Reversal Assist Fork Traverse and Prevent
      Chromosomal Breakage at DNA Interstrand Cross-Links.
AB  - Interstrand cross-links (ICLs) are toxic DNA lesions interfering with DNA
      metabolism that are induced by widely used anticancer drugs. They have long been
      considered absolute roadblocks for replication forks, implicating complex DNA
      repair processes at stalled or converging replication forks. Recent evidence
      challenged this view, proposing that single forks traverse ICLs by yet elusive
      mechanisms. Combining ICL immunolabeling and single-molecule approaches in human
      cells, we now show that ICL induction leads to global replication fork slowing,
      involving forks not directly challenged by ICLs. Active fork slowing is linked to
      rapid recruitment of RAD51 to replicating chromatin and to RAD51/ZRANB3-mediated
      fork reversal. This global modulation of fork speed and architecture requires ATR
      activation, promotes single-fork ICL traverse-here, directly visualized by
      electron microscopy-and prevents chromosomal breakage by untimely ICL processing.
      We propose that global fork slowing by remodeling provides more time for template
      repair and promotes bypass of residual lesions, limiting fork-associated
      processing.

PMID- 30184500
TI  - Cell-to-Cell Heterogeneity in p38-Mediated Cross-Inhibition of JNK Causes
      Stochastic Cell Death.
AB  - The stress-activated protein kinases c-Jun N-terminal kinase (JNK) and p38 are
      important players in cell-fate decisions in response to environmental stress
      signals. Crosstalk signaling between JNK and p38 is emerging as an important
      regulatory mechanism in inflammatory and stress responses. However, it is unknown
      how this crosstalk affects signaling dynamics, cell-to-cell variation, and
      cellular responses at the single-cell level. We established a multiplexed live
      cell imaging system based on kinase translocation reporters to simultaneously
      monitor JNK and p38 activities with high specificity and sensitivity at single
      cell resolution. Various stresses activated JNK and p38 with various dynamics. In
      all cases, p38 suppressed JNK activity in a cross-inhibitory manner. We
      demonstrate that p38 antagonizes JNK through both transcriptional and post
      translational mechanisms. This cross-inhibition generates cellular heterogeneity
      in JNK activity after stress exposure. Our data indicate that this heterogeneity
      in JNK activity plays a role in fractional killing in response to UV stress.

PMID- 30184501
TI  - Ral Signals through a MAP4 Kinase-p38 MAP Kinase Cascade in C. elegans Cell Fate
      Patterning.
AB  - C. elegans vulval precursor cell (VPC) fates are patterned by an epidermal growth
      factor (EGF) gradient. High-dose EGF induces 1 degrees  VPC fate, and lower dose
      EGF contributes to 2 degrees  fate in support of LIN-12/Notch. We previously
      showed that the EGF 2 degrees -promoting signal is mediated by LET-60/Ras
      switching effectors, from the canonical Raf-MEK-ERK mitogen-activated protein
      (MAP) kinase cascade that promotes 1 degrees  fate to the non-canonical RalGEF
      Ral that promotes 2 degrees  fate. Of oncogenic Ras effectors, RalGEF-Ral is by
      far the least well understood. We use genetic analysis to identify an effector
      cascade downstream of C. elegans RAL-1/Ral, starting with an established Ral
      binding partner, Exo84 of the exocyst complex. Additionally, RAL-1 signals
      through GCK-2, a citron-N-terminal-homology-domain-containing MAP4 kinase, and
      PMK-1/p38 MAP kinase cascade to promote 2 degrees  fate. Our study delineates a
      Ral-dependent developmental signaling cascade in vivo, thus providing the
      mechanism by which lower EGF dose is transduced.

PMID- 30184502
TI  - Repression of Somatic Genes by Selective Recruitment of HDAC3 by BLIMP1 Is
      Essential for Mouse Primordial Germ Cell Fate Determination.
AB  - Primordial germ cells (PGCs) are fate determined from pluripotent epiblasts.
      Signaling pathways and transcriptional regulators involved in PGC formation have
      been identified, but detailed molecular mechanisms of PGC fate determination
      remains poorly understood. Using RNAi screening, we identified histone
      deacetylase 3 (HDAC3) as a regulator of PGC formation. Hdac3 deficiency resulted
      in decreased nascent PGCs in vitro and in vivo, and somatic developmental genes
      were de-repressed by Hdac3 knockdown during PGC induction. We also demonstrated
      BLIMP1-dependent enrichment of HDAC3 and deacetylation of H3 and H4 histones in
      the somatic developmental genes in epiblast-like cells. In addition, the
      HDAC3/BLIMP1-targeted somatic gene products were enriched in PGC determinant
      genes; overexpression of these gene products in PGC-like cells in culture
      resulted in repression of PGC determinant genes. We propose that selective
      recruitment of HDAC3 to somatic genes by BLIMP1 and subsequent repression of
      these somatic genes are crucial for PGC fate determination.

PMID- 30184503
TI  - miR-92 Suppresses Robo1 Translation to Modulate Slit Sensitivity in Commissural
      Axon Guidance.
AB  - Temporospatial regulation of guidance signaling is essential for axon outgrowth
      and pathfinding in the developing nervous system. Regulation of Robo1 levels in
      commissural neurons modulates Slit sensitivity facilitating proper axon guidance.
      The mechanisms underlying this regulation in the vertebrate nervous system are
      not well understood. Here, we report that miR-92, a highly conserved microRNA
      (miRNA), regulates chicken Robo1 expression in commissural neurons by binding to
      the 3' untranslated region (3' UTR) of Robo1 mRNA. miR-92 and Robo1 are
      differentially expressed in the developing spinal cord. miR-92 interacts with the
      Robo1 3'UTR to cause translational repression, but not mRNA degradation.
      Disruption of the miR-92/Robo1 3' UTR interaction induces premature
      responsiveness to Slit2 repulsion of precrossing commissural axons (CAs) in vitro
      and causes CA projection defects in vivo. These results indicate that miR-92
      represses Robo1 expression thereby regulating Slit sensitivity to control CA
      projection and midline crossing.

PMID- 30184504
TI  - Rapid Assembly of Presynaptic Materials behind the Growth Cone in Dopaminergic
      Neurons Is Mediated by Precise Regulation of Axonal Transport.
AB  - The proper assembly of neural circuits depends on the process of synaptogenesis,
      or the formation of synapses between partner neurons. Using the dopaminergic PDE
      neurons in C. elegans, we developed an in vivo system to study the earliest steps
      of the formation of en passant presynaptic specializations behind an extending
      growth cone. We find that presynaptic materials coalesce into puncta in as little
      as a few minutes and that both synaptic vesicle (SV) and active zone (AZ)
      proteins arrive nearly simultaneously at the nascent sites of synapse formation.
      We show that precise regulation of UNC-104/Kinesin-3 determines the distribution
      of SV proteins along the axon. The localization of AZ proteins to en passant
      puncta, however, is largely independent of the major axonal kinesins: UNC
      104/Kinesin-3 and UNC-116/Kinesin-1. Moreover, AZ proteins play a crucial role in
      recruiting and tethering SV precursors (SVPs).

PMID- 30184505
TI  - Structural Basis of Pan-Ebolavirus Neutralization by an Antibody Targeting the
      Glycoprotein Fusion Loop.
AB  - Monoclonal antibodies (mAbs) with pan-ebolavirus cross-reactivity are highly
      desirable, but development of such mAbs is limited by a lack of a molecular
      understanding of cross-reactive epitopes. The antibody ADI-15878 was previously
      identified from a human survivor of Ebola virus Makona variant (EBOV/Mak)
      infection. This mAb demonstrated potent neutralizing activity against all known
      ebolaviruses and provided protection in rodent and ferret models against three
      ebolavirus species. Here, we describe the unliganded crystal structure of ADI
      15878 as well as the cryo-EM structures of ADI-15878 in complex with the EBOV/Mak
      and Bundibugyo virus (BDBV) glycoproteins (GPs). ADI-15878 binds through an
      induced-fit mechanism by targeting highly conserved residues in the internal
      fusion loop (IFL), bridging across GP protomers via the heptad repeat 1 (HR1)
      region. Our structures provide a more complete description of the ebolavirus
      immunogenic landscape, as well as a molecular basis for how rare but potent
      antibodies target conserved filoviral fusion machinery.

PMID- 30184506
TI  - Histidine-Dependent Protein Methylation Is Required for Compartmentalization of
      CTP Synthase.
AB  - CTP synthase (CTPS) forms compartmentalized filaments in response to substrate
      availability and environmental nutrient status. However, the physiological role
      of filaments and mechanisms for filament assembly are not well understood. Here,
      we provide evidence that CTPS forms filaments in response to histidine influx
      during glutamine starvation. Tetramer conformation-based filament formation
      restricts CTPS enzymatic activity during nutrient deprivation. CTPS protein
      levels remain stable in the presence of histidine during nutrient deprivation,
      followed by rapid cell growth after stress relief. We demonstrate that filament
      formation is controlled by methylation and that histidine promotes re-methylation
      of homocysteine by donating one-carbon intermediates to the cytosolic folate
      cycle. Furthermore, we find that starvation stress and glutamine deficiency
      activate the GCN2/ATF4/MTHFD2 axis, which coordinates CTPS filament formation.
      CTPS filament formation induced by histidine-mediated methylation may be a
      strategy used by cancer cells to maintain homeostasis and ensure a growth
      advantage in adverse environments.

PMID- 30184508
TI  - Lipidomic Profiles of the Heart and Circulation in Response to Exercise versus
      Cardiac Pathology: A Resource of Potential Biomarkers and Drug Targets.
AB  - Exercise-induced heart growth provides protection against cardiovascular disease,
      whereas disease-induced heart growth leads to heart failure. These distinct forms
      of growth are associated with different molecular profiles (e.g., mRNAs, non
      coding RNAs, and proteins), and targeting differentially regulated genes has
      therapeutic potential for heart failure. The effects of exercise on the cardiac
      and circulating lipidomes in comparison to disease are unclear. Lipidomic
      profiling was performed on hearts and plasma of mice subjected to swim endurance
      training or a cardiac disease model (moderate or severe pressure overload).
      Several sphingolipid species and phospholipids containing omega-3/6 fatty acids
      were distinctly altered in heart and/or plasma with exercise versus pressure
      overload. A subset of lipids was validated in an independent mouse model with
      heart failure and atrial fibrillation. This study highlights the adaptations that
      occur to lipid profiles in response to endurance training versus pathology and
      provides a resource to investigate potential therapeutic targets and biomarkers.

PMID- 30184507
TI  - Flow Cytometry of Mouse and Human Adipocytes for the Analysis of Browning and
      Cellular Heterogeneity.
AB  - Adipocytes, once considered simple lipid-storing cells, are rapidly emerging as
      complex cells with many biologically diverse functions. A powerful high
      throughput method for analyzing single cells is flow cytometry. Several groups
      have attempted to analyze and sort freshly isolated adipocytes; however, using an
      adipocyte-specific reporter mouse, we demonstrate that these studies fail to
      detect the majority of white adipocytes. We define critical settings required for
      adipocyte flow cytometry and provide a rigid strategy for analyzing and sorting
      white and brown adipocyte populations. The applicability of our protocol is shown
      by sorting mouse adipocytes based on size or UCP1 expression and demonstrating
      that a subset of human adipocytes lacks the beta2-adrenergic receptor,
      particularly in the insulin-resistant state. In conclusion, the present study
      confers key technological insights for analyzing and sorting mature adipocytes,
      opening up numerous downstream research applications.

PMID- 30184509
TI  - Transcriptional and Translational Differences of Microglia from Male and Female
      Brains.
AB  - Sex differences in brain structure and function are of substantial scientific
      interest because of sex-related susceptibility to psychiatric and neurological
      disorders. Neuroinflammation is a common denominator of many of these diseases,
      and thus microglia, as the brain's immunocompetent cells, have come into focus in
      sex-specific studies. Here, we show differences in the structure, function, and
      transcriptomic and proteomic profiles in microglia freshly isolated from male and
      female mouse brains. We show that male microglia are more frequent in specific
      brain areas, have a higher antigen-presenting capacity, and appear to have a
      higher potential to respond to stimuli such as ATP, reflected in higher baseline
      outward and inward currents and higher protein expression of purinergic
      receptors. Altogether, we provide a comprehensive resource to generate and
      validate hypotheses regarding brain sex differences.

PMID- 30184511
TI  - Loss of Abhd5 Promotes Colorectal Tumor Development and Progression by Inducing
      Aerobic Glycolysis and Epithelial-Mesenchymal Transition.

PMID- 30184510
TI  - Dynamics of Transcription Regulation in Human Bone Marrow Myeloid Differentiation
      to Mature Blood Neutrophils.
AB  - Neutrophils are short-lived blood cells that play a critical role in host defense
      against infections. To better comprehend neutrophil functions and their
      regulation, we provide a complete epigenetic overview, assessing important
      functional features of their differentiation stages from bone marrow-residing
      progenitors to mature circulating cells. Integration of chromatin modifications,
      methylation, and transcriptome dynamics reveals an enforced regulation of
      differentiation, for cellular functions such as release of proteases, respiratory
      burst, cell cycle regulation, and apoptosis. We observe an early establishment of
      the cytotoxic capability, while the signaling components that activate these
      antimicrobial mechanisms are transcribed at later stages, outside the bone
      marrow, thus preventing toxic effects in the bone marrow niche. Altogether, these
      data reveal how the developmental dynamics of the chromatin landscape orchestrate
      the daily production of a large number of neutrophils required for innate host
      defense and provide a comprehensive overview of differentiating human
      neutrophils.

PMID- 30184512
TI  - Knowledge Translation in Practice: Exploring the Potential Use of MCDA in Central
      America and the Caribbean.
AB  - The interest on Multicriteria decision analysis (MCDA) for healthcare priority
      setting has grown in popularity in the last few years. Literature shows several
      exercises where MCDA can be used to inform different types of priorities;
      however, there is little evidence on the feasibility of implementing this method
      in current institutionalized decision-making processes. We examined the
      willingness to implement MCDA as a tool to facilitate decision-making in Central
      America and the Caribbean (CAC). We convene 41 representatives of the healthcare
      public sector from 10 countries to explore whether they consider MCDA a robust
      tool to be incorporated in local priority setting processes and which ongoing
      decision-making process could be benefited from this methodology. We developed a
      2-days hands-on training course to explain the technique, advantages and
      limitations. The group achieved a broad consensus that MCDA can be used in CAC to
      help priority setting processes because it introduces transparency, facilitates
      the implementation of a systematic process and is relatively easy to explain to
      many stakeholders. It was acknowledged that MCDA can be used to inform decisions
      about coverage, though a major opportunity was identified to help informing other
      decisions, such as priorities for joint purchasing and the elaboration of
      national plans.

PMID- 30184513
TI  - Vitamin D receptor gene polymorphisms modify the association of serum 25
      hydroxyvitamin D levels with handgrip strength in the elderly in Northern China.
AB  - OBJECTIVES: The aim of this cross-sectional study was to investigate the
      association of serum 25-hydroxyvitamin D (25[OH]D) levels and vitamin D receptor
      (VDR) genotypes with skeletal muscle mass and function in elderly subjects in
      northern China. METHODS: A total of 275 men and 510 women, ages 63.1 to 72.5 y,
      in two randomly selected communities in Beijing were investigated. The
      investigation included a questionnaire, physical measurements, muscle mass and
      function measurements, serum 25(OH)D levels, and VDR gene polymorphisms analysis.
      RESULTS: In the group with 25(OH)D levels <10.0 ng/mL, the proportion with low
      handgrip strength was 3.04 times higher than that in the group with 25(OH)D
      levels >20.0 ng/mL for men (odds ratio: 3.04; 95% confidence interval, 1.13-8.20)
      but not for women. The general linear model showed that higher 25(OH)D levels and
      having T allele of Fok1 and the bb genotype of Bsm1 were significantly associated
      with more handgrip strength. The regression coefficients (beta) were 1.80 (P <
      0.01), 1.26 (P < 0.01), and 2.90 (P < 0.01), respectively. There was a
      significant interaction between 25(OH)D and VDR gene polymorphisms for handgrip
      strength for both Fok1 (beta = 2.86; P < 0.01) and Bsm1 (beta = 3.14; P = 0.02)
      after adjustment for potential confounders (sex, age, body mass index, fat mass,
      physical activity, sun exposure, energy, and protein intake). CONCLUSIONS:
      25(OH)D levels are associated with handgrip strength for men and this
      relationship could be modified with the interaction between 25(OH)D and VDR gene
      polymorphisms (Fok1 and Bsm1).

PMID- 30184514
TI  - The use of a food logging app in the naturalistic setting fails to provide
      accurate measurements of nutrients and poses usability challenges.
AB  - OBJECTIVE: MyFitnessPal is the most popular commercial nutrition weight loss app.
      The aim of this study was to assess how individuals in naturalistic settings
      performed when recording their dietary intake in MyFitnessPal, and their
      usability experiences with the app. METHODS: Adults not regularly using
      MyFitnessPal (N = 43) logged their dietary intake in the app for 4 consecutive
      days and completed two researcher-administered 24-h recalls collected based on
      the Automated Multiple Pass Method. Food items from 24-h recalls were coded into
      food categories and foods omitted from corresponding MyFitnessPal records were
      calculated. Comparative validity of energy and macronutrient outputs from
      MyFitnessPal were compared against 24-h recalls using paired t tests. Inductive
      thematic analysis was applied to app usability responses. RESULTS: Individuals
      omitted a mean of 18% (SD, 15) of food items, particularly energy-dense and
      nutrient-poor foods from MyFitnessPal records. Relative to 2-day 24-h recalls, 4
      day MyFitnessPal records significantly underestimated mean energy intake by 1863
      kJ (SD, 2952 kJ, P = 0.0002) and intake of all macronutrients. Although 80% of
      participants rated MyFitnessPal as easy to use, only 20% said they would continue
      use, citing challenges in matching foods, estimating portion size, and logging
      being time-consuming, as affecting motivation for long-term use. CONCLUSIONS:
      Large discrepancies in nutrient measurements from MyFitnessPal indicate
      suboptimal performance with using the app to record intake, particularly given
      food omissions in records and difficulties encountered with app usability
      relating to the food database and input of portion sizes. Stand-alone use of
      MyFitnessPal is therefore cautioned and guidance from dietitians is necessary to
      support use of nutrition apps in collecting accurate dietary data.

PMID- 30184515
TI  - Sarcopenia: The need to establish different cutoff points of fat-free mass for
      the Chilean population.
AB  - OBJECTIVES: International cutoff points for the diagnosis of sarcopenia are not
      applicable to the Chilean population due to previous evidence of a lower lean
      mass and strength in this population. Dual-energy x-ray absorptiometry is used to
      establish fat-free mass cutoff points to define sarcopenia in the Chilean
      population and analyze its association with handgrip strength in older adults.
      METHODS: Appendicular fat-free mass (AFFM) was calculated from 4062 dual-energy x
      ray absorptiometries of healthy Chileans, ages 18 to 99 y. Possible cutoff points
      for sarcopenia were obtained using four methods: A) Normative, -2 standard
      deviation (SD) below mean AFFM/height2 (AFFMI) of adults age <40 y; B) normative 
      1 SD, -1 SD under the average AFFMI of adults age <40 y; C) stratification, 25th
      percentile of the residual distribution obtained with the regression equation to
      predict AFFM in the entire sample; and D) percentage, -2 SD under the average
      skeletal muscle mass/total body mass of individuals age <40 y. Additionally, in a
      subsample of elderly subjects, the correlation between handgrip strength and the
      four calculated cutoff points was analyzed. RESULTS: Using the normative method,
      sarcopenia was defined as an AFFMI <6.4 kg/m2 in men and <4.8 kg/m2 in women and
      at -1 SD, the cutoff points were <7.5 kg/m2 and <5.6 kg/m2, respectively. With
      the stratification method, sarcopenia was defined as -1.33 kg and -1.05 kg of
      AFFM with respect to the expected value according to the regression equation in
      men and women, respectively. According to the percentage method, the cutoff
      points for sarcopenia were <30% and <22.9% in men and women, respectively. The
      concordance of the four methods was slight to moderate. Only the percentage
      method showed a progressive increase in the proportion of subjects with
      sarcopenia as age increased. The latter and the normative -1 DS predicted lower
      handgrip strength in elderly women, unlike the other diagnostic methods. For
      elderly men, only the normative -1 DS method predicted weaker handgrip strength.
      CONCLUSIONS: The AFFM of young Chileans is lower than that reported in Western
      countries but similar to Latin American data; therefore, the use of the
      traditional normative method would not be appropriate with -2 SD to establish
      cutoff points, and using -1 DS resulted in values that are higher than
      Baumgartner's. Stratification is advantageous because this method throws expected
      values of AFFM for each population; however, overdiagnosis of sarcopenia is a
      possibility and thus the method requires a representative sample. The percentage
      method is simple and showed the expected decrease of muscle mass with age, and
      also correlated well with handgrip strength in elderly women. Thus, this method
      represented our method of choice to detect sarcopenia.

PMID- 30184516
TI  - Development of a bedside-applicable ultrasound protocol to estimate fat mass
      index derived from whole body dual-energy x-ray absorptiometry scans.
AB  - OBJECTIVES: Precise measures of adiposity are difficult to obtain in clinical
      settings due to a lack of access to accurate and reliable techniques. The aim of
      this study was to develop and internally validate a bedside-applicable ultrasound
      protocol to estimate fat mass index. METHODS: We conducted an observational cross
      sectional study of 94 university and community dwelling adults who attended a
      single data-collection session. Adipose tissue thickness was quantified in a
      supine or prone position using the four-site protocol (images two anterior sites
      on each thigh) and the nine-site protocol (images nine anterior and posterior
      sites). Adipose tissue thicknesses from the four-site protocol were compared
      against the fat mass index that was derived from dual-energy x-ray absorptiometry
      scans. Subsequently, we optimized the accuracy of the four-site protocol with the
      addition of bedside-accessible adipose tissue thicknesses from the nine-site
      protocol and easily obtained covariates. RESULTS: The four-site protocol was
      strongly associated (R2 = 0.65) with fat mass index but wide limits of agreement
      (-3.53 kg/m2 and 3.50 kg/m2) were observed using the Bland-Altman analysis. With
      the addition of the anterior upper arm and abdomen adipose tissue thicknesses as
      well as the covariates age, sex, and body mass index, the model accuracy improved
      (R2 = 0.93) and the Bland-Altman analysis displayed narrower limits of agreement
      (-1.57 kg/m2 and 1.60 kg/m2). CONCLUSIONS: This optimized protocol developed can
      be applied bedside and provide accurate assessments of fat mass index.

PMID- 30184517
TI  - Amino acid profile after oral nutritional supplementation in hemodialysis
      patients with protein-energy wasting.
AB  - OBJECTIVES: Protein-energy wasting (PEW) is highly prevalent in patients on
      hemodialysis (HD). Oral nutritional supplementation (ONS) is recommended for
      malnourished patients on HD. The aim of this study was to evaluate ONS on plasma
      amino acid in HD patients with PEW. METHODS: Thirty-two HD patients with a mean
      age 59.1 +/- 9.5 y with PEW were enrolled into the study. Patients were
      prescribed ONS (125 mL twice a day for 3 mo) together with dietary advice. The
      nutritional status was evaluated by means of body mass index, Subjective Global
      Assessment, and serum albumin and prealbumin levels. The percentages of body fat
      and lean body mass were measured by means of the near-infrared method. The lean
      body mass-to-body weight ratios were calculated. Tumor necrosis factor,
      interleukin-6 and high-sensitivity C-reactive protein, were measured by the
      enzyme-linked immunosorbent assay method. Serum concentrations of amino acids
      were measured by the high-performance liquid chromatography method. RESULTS:
      After 3 mo of ONS, a significant increase of both serum prealbumin and albumin
      was observed. The concentration of most of the amino acids increased
      independently on inflammation. CONCLUSIONS: Dietary advice, combined with ONS, is
      effective in HD patients with PEW. Both dietary advice and ONS are needed to be
      sure that patients consume an adequate daily amount of calories and protein.

PMID- 30184518
TI  - Comparison between red wine and isolated trans-resveratrol on the prevention and
      regression of atherosclerosis in LDLr (-/-) mice.
AB  - Moderate consumption of red wine has been widely associated with reduced
      cardiovascular risk, mainly due to its composition in phenolic compounds with
      antioxidant activity, such as resveratrol. The objective of this study was to
      compare the effect of red wine vs. trans-resveratrol consumption on the
      prevention and regression of atherosclerosis in LDLr (-/-) mice. This study
      consisted of two protocols: "Prevention" (PREV) and "Regression" (REGR). Both
      protocols included four groups: red wine (WINE), dealcoholized red wine (EXT),
      trans-resveratrol (RESV), and control (CONT). In PREV protocol, animals received
      a regular diet for 8 weeks and then switched to an atherogenic diet for the
      following 8 weeks, while the opposite was performed in REGR. Animals that
      received atherogenic diet after an initial period of standard diet (PREV) gained
      more body weight (39.25+/-2.30%) than the opposite (29.27+/-1.91%, P=.0013),
      suggesting an interaction between age and weight gain. Trans-resveratrol showed
      the highest hypocholesterolemic effect during PREV, reducing total cholesterol,
      LDL-C, VLDL-C and HDL-C. Supplementation with trans-resveratrol and dealcoholized
      red wine changed the fatty acids profile in the liver in both protocols, leading
      to an increase of MDA concentrations and SOD activity in the PREV protocol. In
      conclusion, supplementation with trans-resveratrol, red wine and the same wine
      without alcohol altered biomarkers of oxidative stress and lipidemia but had no
      effect on the prevention or regression of fatty streaks. These data suggest that
      cardiovascular protection associated with the "French Paradox" may be a result of
      synergistic effects between wine and the Mediterranean diet.

PMID- 30184519
TI  - The identification and health risk assessment of odor emissions from waste
      landfilling and composting.
AB  - Odor nuisance is the main incentive for Not In My Back Yard campaigns around
      municipal solid waste (MSW) waste disposal facilities, and the odor
      identification is of significance for the understanding of the odor properties
      from MSW with different disposal methods. In this study, odor emissions from
      different stages at two large-scale working MSW disposal facilities, i.e.,
      landfill (LF) and compost plant (CP), were distinguished with the same MSW
      feedstock in one city. It was found that CP suffered the heavier odor pollution
      and the characteristics of odorants changed significantly, especially the pile
      turning workshop. Sulfides and aromatics were the main concentration contributors
      for LF, while that for CP were NH3 and oxygenated compounds. Significant
      correlations between odor concentration and halogenated compounds, sulfides (r2 =
      0.945, 0.898, p<0.05, n = 12) were merely observed in CP. The priority odor
      pollutants of LF were H2S, benzene and NH3, while that of CP was NH3, ethyl
      acetate and benzene with a descending order. With regarding to their
      contributions for occupational exposure, the carcinogenic risk was negligible for
      these facilities, but H2S of LF might bring non-carcinogenic risk to on-site
      workers.

PMID- 30184520
TI  - Chemical source profiles of urban fugitive dust PM2.5 samples from 21 cities
      across China.
AB  - Urban fugitive (road and construction) dust PM2.5 samples were collected in 21
      cities of seven regions in China. Seven water-soluble ions, eight sub-fractions
      of carbonaceous components, and 19 elements were determined to investigate the
      chemical profiles of urban fugitive dust. Among the analyzed chemical
      compositions and on regional average, the elemental compositions showed the
      highest proportion (12.5-28.9% in road dust (RD) and 13.1-38.0% in construction
      dust (CD)), followed by water-soluble ions (5.1-19.0% in RD and 4.2-16.4% in CD)
      and carbonaceous fractions (5.4-9.6% in RD and 4.9-9.3% in CD). Chemical
      compositions measured in CD were all slightly lower than those in RD although
      statistically insignificant (p > 0.05). Soil dust, which was estimated from Fe
      concentration, was proved to be the biggest contributor to urban fugitive dust
      PM2.5 mass. While, it showed a higher contribution in Northern China (71.5%) than
      in Southern China (52.1%). Higher enrichment factors were found for elemental S,
      Zn and Pb in RD than CD, reflecting stronger anthropogenic sources (i.e. vehicle
      exhaust) in RD. Low NO3-/SO42- and high SO42-/K+ ratios both indicated that
      fugitive dust was strongly influenced by stationary sources (e.g. coal
      combustion), and this influence was especially strong in Northern China.
      Coefficients of divergence proved that dust profiles within the same region were
      more similar than across regions, reflecting that urban fugitive dust was
      influenced more by local sources than long-range transport.

PMID- 30184521
TI  - Have We Made "Rapid Progress" Understanding the Pathogenesis in Rapidly
      Progressive Glomerulonephritis?

PMID- 30184522
TI  - Atypical Phenotype and Treatment Response Pattern in a Patient with FIP1L1
      PDGFRalpha Mutation.
AB  - Myeloproliferative disorders with eosinophilia may possess the FIP1L1-PDGFRalpha
      gene rearrangement. When this rearrangement is present, imatinib usually results
      in complete remission. In rare cases of imatinib resistance, there is poor
      evidence guiding second-line therapy. We present the case of a 71-year-old male
      who presented with abdominal discomfort, fevers, and leukocytosis with
      eosinophilia. The patient was diagnosed with a myeloproliferative neoplasm with
      eosinophilia and FIP1L1-PDGFRalpha rearrangement after a bone marrow evaluation
      revealed hypercellular marrow with eosinophilia and fluorescence in situ
      hybridization identified the FIP1L1-PDGFRalpha rearrangement. The patient was
      successfully treated with imatinib. Within months he relapsed and converted into
      acute myeloid leukemia. The patient was then treated with ponatinib which induced
      and maintained clinical and hematological remission for 2 months. That ponatinib
      briefly induced remission in our patient with acute myeloid leukemia arising from
      a myeloproliferative neoplasm with eosinophilia and FIP1L1-PDGFRalpha fusion may
      merit exploration of ponatinib as a potential second-line treatment option for
      this patient population. This is especially true given the lack of reliable
      therapies in instances of imatinib resistance.

PMID- 30184523
TI  - Application of Photoacoustic Methods and Confocal Microscopy for Monitoring of
      Therapeutic Response in Plaque Psoriasis.
AB  - Psoriasis is prone to relapses and requires long-term therapy that may induce a
      range of adverse effects; therefore, an efficient and early detection of relapses
      is desirable. In this study, photoacoustic imaging and confocal laser scanning
      microscopic (CLSM) methods were investigated for their suitability in psoriasis
      follow-up examinations. Using a high-resolution photoacoustic system, the
      vascular structures of 11 psoriatic patients and 6 healthy volunteers were
      investigated. No differences were detected with respect to the average vessel
      diameter and vasculature per unit volume in the tissue of healthy volunteers and
      non-lesional and lesional skin areas of psoriatic patients. By means of CLSM, the
      diameters of the dermal papillae of 6 volunteers and 6 psoriatic patients were
      determined. The diameters of the dermal papillae of the healthy volunteers (0.074
      +/- 0.006 mm) revealed no significant difference when compared to non-lesional
      skin areas of psoriatic patients (0.079 +/- 0.005 mm). The results obtained for
      the lesions in psoriatic patients showed a significant difference (Wilcoxon test,
      p = 0.028) between the diameters of the dermal papillae of the lesional skin
      areas (0.114 +/- 0.012 mm) and the non-lesional skin areas (0.079 +/- 0.005 mm).
      Thus, CLSM can be applied for monitoring psoriasis follow-up examinations.

PMID- 30184524
TI  - Sunitinib or Sorafenib as Neoadjuvant Therapy May not Improve the Survival
      Outcomes of Renal Cell Carcinoma with Tumor Thrombus.
AB  - OBJECTIVES: The purpose of this work was to investigate the effect of sorafenib
      or sunitinib as neoadjuvant therapy on the survival outcomes of renal cell
      carcinoma (RCC) with tumor thrombus. METHODS: A total of 92 RCC patients with
      tumor thrombus were included in this 2-center retrospective research from January
      2007 to December 2014. Sorafenib and sunitinib were administered as neoadjuvant
      therapy in 9 patients and 14 patients, respectively, and 69 patients constituted
      non-neoadjuvant therapy groups. The Kaplan-Meier method was used to estimate the
      recurrence-free survival (RFS) and overall survival (OS). Log-rank test was used
      to compare the survival outcomes of patients with or without neoadjuvant therapy.
      RESULTS: The overall median RFS and OS time for all 92 patients were 28 months
      (95% CI 17-39 months) and 42 months (95% CI 30-54 months). Patients with
      neoadjuvant therapy had no significantly longer median RFS (30 vs. 28 months, p =
      0.376) and OS (45 vs. 42 months, p = 0.702) than those without neoadjuvant
      therapy. CONCLUSIONS: Neoadjuvant therapy of sorafenib or sunitinib might not
      improve survival outcomes for high risk RCC patients with tumor thrombus. Thus,
      neoadjuvant therapy for RCC with tumor thrombus should be considered cautiously.

PMID- 30184525
TI  - Early Introduction of Egg and the Development of Egg Allergy in Children: A
      Systematic Review and Meta-Analysis.
AB  - BACKGROUND: The timing of the introduction of egg to an infant's diet is of
      current interest, as new evidence raises questions regarding the benefit of
      delaying egg introduction. The objective of this study was to systematically
      review the existing literature regarding the effect of the early introduction of
      egg on the development of egg allergy. METHODS: Literature searches were
      conducted in MEDLINE, EMBASE, and CENTRAL, and trial protocols were searched in
      Meta Register and OpenGREY. Only randomized controlled trials (RCTs) comparing
      early (between 3 and 6 months of age) egg introduction to no early introduction
      were included. The primary outcome was the development of egg allergy. RESULTS:
      Of the 416 articles identified and screened, 6 RCTs met the eligibility criteria
      for data extraction. Allergic outcomes were evaluated in a total of 3,032
      participants. A low to moderate level of evidence showed a benefit of the early
      introduction of egg (relative risk, RR 0.60, 95% CI 0.44-0.82, p = 0.002, mild
      heterogeneity, I2 = 23%). The absolute risk reduction for a population with an
      incidence of egg allergy of 9.3% was 37 fewer cases (95% CI 17-52) per 1,000
      people. Consumption of < 4,000 mg/week of egg protein had a greater preventive
      effect than a higher dose. CONCLUSION: This systematic review and meta-analysis
      showed an association between the early introduction of egg and a lower risk of
      egg allergy. Furthermore, the nature and dose of egg protein exposure may play a
      role. These findings should be addressed in the context of primary studies.

PMID- 30184526
TI  - MicroRNA High Throughput Loss-of-Function Screening Reveals an Oncogenic Role for
      miR-21-5p in Hodgkin Lymphoma.
AB  - BACKGROUND/AIMS: Classical Hodgkin lymphoma (cHL) is among the most frequent
      lymphoma subtypes. The tumor cells originate from crippled germinal center (GC)-B
      cells that escaped from apoptosis. MicroRNAs (miRNAs) play important roles in B
      cell maturation and aberrant expression of miRNAs contributes to the pathogenesis
      of cHL. Our aim was to identify oncogenic miRNAs relevant for growth of cHL using
      a high-throughput screening approach. METHODS: A lentiviral pool of 63 miRNA
      inhibition constructs was used to identify miRNAs essential to cell growth in
      three cHL cell lines in duplicate. As a negative control we also infected cHL
      cell lines with a lentiviral barcoded empty vector pool consisting of 222
      constructs. The abundance of individual constructs was followed over time by a
      next generation sequencing approach. The effect on growth was confirmed using
      individual GFP competition assays and on apoptosis using Annexin-V staining. Our
      previously published Argonaute 2 (Ago2) immunoprecipitation (IP) data were used
      to identify target genes relevant for cell growth / apoptosis. Luciferase assays
      and western blotting were performed to confirm targeting by miRNAs. RESULTS: Four
      miRNA inhibition constructs, i.e. miR-449a-5p, miR-625-5p, let-7f-2-3p and miR-21
      5p, showed a significant decrease in abundance in at least 4 of 6 infections. In
      contrast, none of the empty vector constructs showed a significant decrease in
      abundance in 3 or more of the 6 infections. The most abundantly expressed miRNA,
      i.e. miR-21-5p, showed significantly higher expression levels in cHL compared to
      GC-B cells. GFP competition assays confirmed the negative effect of miR-21-5p
      inhibition on HL cell growth. Annexin-V staining of cells infected with miR-21-5p
      inhibitor indicated a significant increase in apoptosis at day 7 and 9 after
      viral infection, consistent with the decrease in growth. Four miR-21-5p cell
      growth- and apoptosis-associated targets were AGO2-IP enriched in cHL cell lines
      and showed a significant decrease in expression in cHL cell lines in comparison
      to normal GC-B cells. For the two most abundantly expressed, i.e. BTG2 and PELI1,
      we confirmed targeting by miR-21-5p using luciferase assays and for PELI1 we also
      confirmed this at the protein level by western blotting. CONCLUSION: Using a
      miRNA loss-of-function high-throughput screen we identified four miRNAs with
      oncogenic effects in cHL and validated the results for the in cHL abundantly
      expressed miR-21-5p. MiR-21-5p is upregulated in cHL compared to GC-B cells and
      protects cHL cells from apoptosis possibly via targeting BTG2 and PELI1.

PMID- 30184527
TI  - ALDH1 Expression and Vasculogenic Mimicry Are Positively Associated with Poor
      Prognosis in Patients with Breast Cancer.
AB  - BACKGROUND/AIMS: This study aimed to explore the prognostic value of aldehyde
      dehydrogenase 1 (ALDH1) expression and vasculogenic mimicry (VM) in patients with
      breast cancer. METHODS: ALDH1 expression and the presence of VM were examined by
      immunohistochemistry and CD31/PAS double staining, respectively, using formalin
      fixed paraffin-embedded tissues from 202 breast cancer patients. The mean follow
      up period ranged from 15 to 115 months. The Kaplan-Meier method was used to plot
      survival curves. Prognostic values were assessed by multivariate analysis using
      the Cox regression model. RESULTS: ALDH1 expression was strongly associated with
      VM (P = 0.005). ALDH1 expression was positively correlated with histological
      grade (P = 0.011). Both ALDH1 expression and VM were negatively related to the
      status of the estrogen receptor and progesterone receptor and were statistically
      increased in triple-negative breast cancer. Patients with ALDH1 expression or VM
      displayed poorer disease-free survival (DFS) and overall survival (OS) than ALDH1
      negative or VM-negative patients, with the worst OS and DFS observed in ALDH1/VM
      double-positive patients. ALDH1-positive and VM-positive were independent
      survival risk factors for DFS and OS. CONCLUSION: ALDH1 expression and VM are
      correlated with the survival rate of patients with breast cancer. ALDH1 and VM,
      either alone or together, are prognostic factors in patients with breast cancer.

PMID- 30184528
TI  - Hypoxia-Regulated miR-146a Targets Cell Adhesion Molecule 2 to Promote
      Proliferation, Migration, and Invasion of Clear Cell Renal Cell Carcinoma.
AB  - BACKGROUND/AIMS: miR-146a has recently been shown to promote cell proliferation,
      migration, and invasion in many cancers, but the role of miR-146a in clear cell
      renal cell carcinoma (ccRCC) remains unclear. METHODS: Reverse transcription
      quantitative PCR (RT-qPCR) was performed to investigate the mRNA expression of
      miR-146a and CADM2 in ccRCC tissues. The luciferase reporter assay, Western
      blotting, and ChIP assay were carried out to explore the promoter and the
      transcription factor of miR-146a. Moreover, the effect of miR-146a and CADM2 on
      ccRCC cells was explored using methyl thiazolyl tetrazolium, colony formation,
      and migration and invasion assays. The luciferase reporter assay, RT-qPCR,
      western blotting, and immunofluorescence assay were carried out to investigate
      whether CADM2 is directly regulated by miR-146a. A tumor xenograft model and
      immunohistochemical staining were used to examine the carcinogenic effect of miR
      146a and CADM2 in vivo. RESULTS: miR-146a has been shown to promote cell
      proliferation, migration, and invasion. Here, we found that miR-146a is highly
      expressed in ccRCC tissues, whereas CADM2 is down-regulated. Hypoxia can induce
      the expression of miR-146a by stimulating its promoter. In addition, we
      demonstrated that miR-146a promoted and CADM2 inhibited proliferation, migration,
      and invasion of ccRCC cells. The 3' untranslated region (UTR) luciferase reporter
      assay identified that miR-146a targeted the 3' UTR of CADM2 and negatively
      regulated its expression. Ectopic expression of CADM2 counteracted the promoting
      effect of miR-146a on cell proliferation, migration, invasion, and the epithelial
      mesenchymal transition process. CONCLUSION: Together, the finding of down
      regulation of CADM2 by miR-146a can provide new insights into ccRCC pathogenesis
      and might contribute to the development of novel therapeutic strategies.

PMID- 30184530
TI  - miR-137 Inhibits Proliferation and Metastasis of Hypertrophic Scar Fibroblasts
      via Targeting Pleiotrophin.
AB  - BACKGROUND/AIMS: There are few effective treatment options for hypertrophic
      scars. MircoRNAs are a class of small, noncoding RNAs involved in multiple
      biological functions. METHODS: Gene chip screening was used to screen out the
      differential expression of miRNAs in hypertrophic scars and normal tissues.
      Western blot and real-time PCR were used to confirm the expression of
      pleiotrophin (PTN) in hypertrophic scars. After analyze the correlation between
      PTN and miR-137 using correlation analysis, we used miRDB software to analyze the
      binding sites of miR-137 and PTN. Luciferase reporter gene, western blot and real
      time PCR experiments were used to detect the regulatory effect of miR-137 on PTN.
      MTT and transwell assay were used to detect the effect of miR-137 on
      proliferation and metastasis. Western blot and real-time PCR were used to detect
      the regulatory effects of miR-137 on cyclin B1, matrix metalloproteinase 9
      (MMP9), alpha-smooth muscle actin (alpha-SMA), vimentin, and type-I collagen
      (COL1A). Finally, miR-137 inhibitor was transfected into fibroblasts which was
      silent PTN, and the proliferation and migration of cells were detected by MTT and
      transwell. Western blot and real-time PCR were used to detect the expression of
      related proteins. RESULTS: Various miRNAs was abnormal expressed in hypertrophic
      scars. miR-137 was decreased in hypertrophic scar, however PTN was up regulated
      in hypertrophic scars. miR-137 induced proliferation and metastasis in
      fibroblasts. This effect was accompanied by decreased expression of cyclin B1,
      MMP9, alpha-SMA, vimentin, and COL1A mediated via the target of PTN. CONCLUSION:
      Modulation of miR-137 expression in fibroblasts could provide an important
      therapeutic strategy for hypertrophic scars.

PMID- 30184529
TI  - Lentiviral Vector-Mediated SHC3 Silencing Exacerbates Oxidative Stress Injury in
      Nigral Dopamine Neurons by Regulating the PI3K-AKT-FoxO Signaling Pathway in Rats
      with Parkinson's Disease.
AB  - BACKGROUND/AIMS: Parkinson's disease (PD) is a prevalent disease that leads to
      motor and cognitive disabilities, and oxidative stress (OS) injury was found to
      be related to the etiology of PD. Increasing evidence has shown that SHC3 is
      aberrantly expressed in neurons. The current study examines the involvement of
      SHC3 silencing in OS injury in the nigral dopamine neurons in rats with PD via
      the PI3K-AKT-FoxO signaling pathway. METHODS: To study the mechanisms and
      functions of SHC3 silencing in PD at the tissue level, 170 rats were selected,
      and a lentivirus-based packaging system was designed to silence SHC3 expression
      in rats. Furthermore, PC12 cells were selected for in vitro experimentation. To
      evaluate the effect of SHC3 silencing in nigral dopamine neuronal growth, an MTT
      assay, propidium iodide (PI) single staining and Annexin V-PI double staining
      were performed to detect cell viability, cell cycle progression and cell
      apoptosis, respectively. RESULTS: SHC3 shRNA led to decreased SOD and MDA levels
      and enhanced GSH activity, indicating that SHC3 silencing leads to motor
      retardation. SHC3 silencing repressed the extent of Akt and FoxO phosphorylation,
      thereby inhibiting the PI3K-AKT-FoxO signaling pathway. Furthermore, in cell
      experiments, SHC3 silencing suppressed PC12 cell proliferation and cell cycle
      progression, whereas it enhanced cell apoptosis. CONCLUSION: The current study
      provides evidence suggesting that SHC3 silencing may aggravate OS injury in
      nigral dopamine neurons via downregulation of the PI3K-AKT-FoxO signaling pathway
      in PD rats.

PMID- 30184532
TI  - Comparison of Pain Characteristics in Patients with Rheumatoid Arthritis and
      Systemic Sclerosis with Particular Reference to Neuropathic Pain Component: Cross
      Sectional Study.
AB  - OBJECTIVE: To compare characteristics of pain in terms of neuropathic pain and to
      assess association between neuropathic component and quality of life (QoL) in
      patients with systemic sclerosis (SSc) and rheumatoid arthritis (RA). SUBJECTS
      AND METHODS: Fifty-four patients (47 females, 7 males) with systemic sclerosis
      and 53 patients (46 females,7 males) with RA were assessed for outcome measures
      including disease activity, physical functions, mental condition and health
      related QoL measures (SF-36; Hospital Anxiety and Depression Scale) and pain.
      Neuropathic pain was assessed by Douleur Neuropathique 4 (DN4) questionnaire and
      PainDetect questionnaire in this cross-sectional study. RESULTS: Patients had
      similar education, smoking status, functioning and HRQoL. However, patients with
      RA declared more severe visual analogue scale of pain, and higher body mass index
      than SSc. Neuropathic pain (NeP) component was detected in 42.6% (n = 23) in SSc,
      and 45.3% (n = 24) in RA (p > 0.05) according to DN4. On PainDetect, possible
      neuropathic pain was detected in 13.0% (n = 7) vs 15.1% (n = 8), whereas 16.7% (n
      = 9) vs 17.0% (n = 9) had likely NeP in SSc and RA, respectively (p > 0.05). Most
      of the neuropathic pain characteristics were similar in SSc and RA except for
      numbness and painful cold which were notably more common in patients with SSc.
      Having neuropathic pain component (according to DN4) had no influence on
      functioning and HRQoL in SSc, however NeP component revealed a heavier burden of
      disease regarding functional status, HRQoL and psychometric components in RA.
      CONCLUSION: The neuropathic pain component was similar between patients with SSc
      and RA. However neuropathic pain was associated with a heavier burden of disease
      in patients with RA.

PMID- 30184531
TI  - YXQ-EQ Induces Apoptosis and Inhibits Signaling Pathways Important for Metastasis
      in Non-Small Cell Lung Carcinoma Cells.
AB  - BACKGROUND/AIMS: Lung cancer is one of the most prevalent malignancies in the
      world. The 5-year survival rate for non-small cell lung cancer (NSCLC) patients
      is only approximately 15%, with metastasis as the primary cause of death. This
      study was aimed to investigate cytotoxic effect of external qi of Yan Xin Qigong
      (YXQ-EQ) toward human lung adenocarcinoma A549 cells as well as its effect on
      signaling pathways promoting migration, invasion and epithelial-to-mesenchymal
      transition (EMT) in A549 cells. METHODS: Cytotoxic effect of YXQ-EQ was evaluated
      using MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4
      sulfophenyl)-2H-tetrazolium, inner salt] and cologenic assays. Apoptosis of
      treated cells was determined by Annexin V/propidium iodide staining and flow
      cytometry analysis, while cell migration and invasion were determined using
      transwell assays and EMT was assessed by morphological changes in cells. Protein
      expression and phosphorylation were examined by immunoblot analyses. RESULTS: YXQ
      EQ induced apoptosis in A549 cells, resulting in a pronounced reduction in
      viability and clonogenic formation. This was associated with inhibition of
      phosphorylation of AKT and ERK1/2 and reduced expression of anti-apoptotic
      proteins BCL-xL, XIAP and survivin. Furthermore, YXQ-EQ inhibited EGF/EGFR
      signaling and EGF mediated migration and invasion of A549 cells. While TGF-beta1
      induced phosphorylation of SMAD2/3 and EMT in A549 cells, YXQ-EQ suppressed TGF
      beta/SMAD signaling and induced cell death in these cells in the presence of TGF
      beta1. CONCLUSION: Our findings suggest that YXQ-EQ could exert anti-lung cancer
      effects via inhibiting signaling pathways that are important for NSCLC cell
      survival and NSCLC metastasis.

PMID- 30184533
TI  - A High-Protein/Low-Fat Diet May Interact with Vitamin D-Binding Protein Gene
      Variants to Moderate the Risk of Depression in Apparently Healthy Adults.
AB  - BACKGROUND: Recent studies have shown that depression is inversely correlated
      with high protein and low fat intake and positively correlated with vitamin D
      binding protein (VDBP). Therefore, the aim of this study was to examine the
      interaction between protein/fat dietary patterns and VDBP genotypes with regard
      to the risk of depression in apparently healthy adults who have not been
      diagnosed with any chronic disease. METHODS: In this study, 265 individuals (126
      males and 139 females) aged 18-55 years were recruited from the communities of
      central and west Tehran based on convenience sampling. Body composition was
      measured with a body composition analyzer and depression symptoms were
      categorized as normal, moderate depression, or severe depression using the
      Depression Anxiety Stress Scales 21 (DASS-21) questionnaire. Dietary patterns
      were determined by a semiquantitative food frequency questionnaire to assess
      typical food intake during the 12-month period. Blood samples were collected from
      and biochemical measurements performed on all participants. An analysis of two
      polymorphisms (rs7041 and rs4588) in the GC gene, which encodes VDBP, was
      performed by polymerase chain reaction-restriction fragment length polymorphism.
      RESULTS: A statistically significant association was found between depression and
      diet (p = 0.03) after having categorized the participants into three groups: a
      high-protein/low-fat (HP/LF) group, a moderate-protein/moderate-fat (MP/MF)
      group, and a low-protein/high-fat (LP/HF) group. Moreover, the findings
      demonstrated that depression was related to both the rs7041 and the rs4588
      polymorphism (p = 0.05 and p = 0.02, respectively). We next used multinomial
      logistic modeling to investigate the risk of depression. A significant
      interaction was observed between HP/LF diet and the rs7041 polymorphism in the
      moderate- and severe-depression groups (beta = -0.30, p = 0.05, and beta = -0.48,
      p = 0.01, respectively). CONCLUSION: This study showed that an HP/LF diet
      interacts with the rs7041 polymorphism, with T allele carriers having a greater
      prevalence of moderate and severe depression.

PMID- 30184534
TI  - Combined Enteral and Parenteral Glutamine Supplementation in Endotoxaemic Swine:
      Effects on Portal and Systemic Circulation Levels.
AB  - OBJECTIVE: To measure plasma GLN levels in systemic and portal circulation after
      combined enteral and parenteral administration in early endotoxemic swine. We
      hypothesized that this combination will be more efficient than intravenous alone
      in restoring plasma levels during the course of endotoxemia. MATERIALS AND
      METHODS: Endotoxemia was induced with E. coli O111:B4 LPS (250 MUg/kgBW) in 16
      anesthetised, fasted swine and maintained by constant infusion (2 MUg/kg/hr) over
      180min. Another 16 swine served as controls. After infusion with LPS or placebo,
      GLN was administered intravenously, enterally or in combination (0.5 g/kg iv plus
      0.5 g/kg enterally) over 30min. At 0, 15, 30, 45, 60, 120 and 180min, blood was
      drawn from the systemic and portal circulation for colorimetric assessment of
      GLN. RESULTS: In healthy, placebo-alone swine, GLN levels remained stable
      throughout the study. Intravenous, and combined infusion increased systemic
      levels (p = 0.001), but after enteral alone, a smaller effect was observed (p =
      0.026). Portal levels were increased after combined, enteral and intravenous
      administration (p = 0.001). In endotoxemia, systemic and portal levels decreased
      significantly. Intravenous, and to a greater extent, combined administration
      increased systemic levels (p = 0.001), while enteral only had a small effect (p =
      0.001). In the portal vein, intravenous and combined treatment increased plasma
      levels (p = 0.001), whereas enteral supplementation alone had again a small, yet
      significant effect (p = 0.001). CONCLUSIONS: The findings indicate that combined
      GLN supplementation is superior to intravenous alone, in terms of enhanced
      availability in systemic and portal circulations. Thus, combined treatment at the
      onset of endotoxemia is a beneficial practice, ensuring adequate GLN to
      compensate for the resulting intracellular shortage.

PMID- 30184535
TI  - Butein Activates Autophagy Through AMPK/TSC2/ULK1/mTOR Pathway to Inhibit IL-6
      Expression in IL-1beta Stimulated Human Chondrocytes.
AB  - BACKGROUND/AIMS: Butein (2',3,4,4'-Tetrahydroxychalcone), a polyphenol produced
      by several plants including Butea monoserpma, has been reported to exert potent
      anti-inflammatory activity but the mechanism remains unknown. In the present work
      we investigated the mechanism of Butein-mediated suppression of IL-6 expression
      in normal and human osteoarthritis (OA) chondrocytes under pathological
      conditions. METHODS: Expression level of interleukin-6 (IL-6) protein in OA
      cartilage was analyzed by immunohistochemistry using a validated antibody.
      Chondrocytes derived from normal or OA cartilage by enzymatic digestion were
      pretreated with Butein followed by stimulation with interleukin-1beta (IL-1beta)
      and the levels of IL-6 mRNA were quantified by TaqMan assay and the protein
      levels were measured by Western immunoblotting. Autophagy activation was
      determined by Western blotting and confocal microscopy. Autophagy was inhibited
      by siRNA mediated knockdown of ATG5. RESULTS: Expression of IL-6 protein was high
      in the OA cartilage compared to smooth cartilage from the same patient. OA
      chondrocytes and cartilage explants stimulated with IL-1beta showed high level
      expression of IL-6 mRNA and protein. Butein increased the phosphorylation of
      AMPKalphaThr-172, TSC2Ser-1387 and ULK1Ser-317 and inhibited the phosphorylation
      of mTORSer-2448 and its downstream target p70S6K and increased autophagy flux
      that correlated with the suppression of the IL-1beta mediated expression of IL-6
      in normal and OA chondrocytes. In OA chondrocytes with siRNA-mediated knockdown
      of ATG5 expression, treatment with Butein failed to activate autophagy and
      abrogated the suppression of IL-1beta induced IL-6 expression. CONCLUSION: Our
      findings demonstrate for the first time that Butein activate autophagy in OA
      chondrocytes via AMPK/TSC2/ULK1/mTOR pathway. Additionally, activation of
      autophagy was essential to block the IL-1beta-induced expression of IL-6 in OA
      chondrocytes. These data support further studies to evaluate the use of Butein or
      compounds derived from it for the management of OA.

PMID- 30184536
TI  - Pacifiers, Thumb Sucking, Breastfeeding, and Bottle Use: Oral Sucking Habits of
      Children with and without Phonological Impairment.
AB  - AIMS: The aim of this study was to describe the nutritive and non-nutritive oral
      sucking habits (breastfeeding, bottle use, pacifier/dummy/soother use,
      thumb/finger sucking) of preschoolers with and without phonological impairment,
      and to determine whether oral sucking habits are associated with the presence and
      severity of phonological impairment. METHODS: We conducted a cross-sectional
      study of 199 Australian English-speaking preschoolers with and without
      phonological impairment. Preschoolers' speech was directly assessed, and
      parents/caregivers completed a questionnaire. Chi-square (chi2) tests were used
      to examine relationships between oral sucking habits and the presence and
      severity of phonological impairment. RESULTS: Based on caregiver reports, 79.9%
      of participants had been breastfed (33.3% for >12 months), 58.3% had used a
      pacifier (74.2% for >=12 months), 83.9% had used a bottle (73.4% for > 12
      months), and 15.1% sucked their thumb/fingers. There was no association between a
      history of oral sucking and the presence and severity of phonological impairment.
      CONCLUSION: The majority of preschoolers had been breastfed and bottle-fed, and
      more than half had used a pacifier. The findings support an understanding that
      phonological impairment is not associated with a history of nutritive and non
      nutritive sucking habits. Research is needed to examine the association between
      oral sucking habits and other types of speech sound disorders.

PMID- 30184537
TI  - C. Elegans Fatty Acid Two-Hydroxylase Regulates Intestinal Homeostasis by
      Affecting Heptadecenoic Acid Production.
AB  - BACKGROUND/AIMS: The hydroxylation of fatty acids at the C-2 position is the
      first step of fatty acid alpha-oxidation and generates sphingolipids containing 2
      hydroxy fatty acyl moieties. Fatty acid 2-hydroxylation is catalyzed by Fatty
      acid 2-hydroxylase (FA2H) enzyme. However, the precise roles of FA2H and fatty
      acid 2-hydroxylation in whole cell homeostasis still remain unclear. METHODS:
      Here we utilize Caenorhabditis elegans as the model and systemically investigate
      the physiological functions of FATH-1/C25A1.5, the highly conserved worm homolog
      for mammalian FA2H enzyme. Immunostaining, dye-staining and translational fusion
      reporters were used to visualize FATH-1 protein and a variety of subcellular
      structures. The "click chemistry" method was employed to label 2-OH fatty acid in
      vivo. Global and tissue-specific RNAi knockdown experiments were performed to
      inactivate FATH-1 function. Lipid analysis of the fath-1 deficient mutants was
      achieved by mass spectrometry. RESULTS: C. elegans FATH-1 is expressed at most
      developmental stages and in most tissues. Loss of fath-1 expression results in
      severe growth retardation and shortened lifespan. FATH-1 function is crucially
      required in the intestine but not the epidermis with stereospecificity. The
      "click chemistry" labeling technique showed that the FATH-1 metabolites are
      mainly enriched in membrane structures preferable to the apical side of the
      intestinal cells. At the subcellular level, we found that loss of fath-1
      expression inhibits lipid droplets formation, as well as selectively disrupts
      peroxisomes and apical endosomes. Lipid analysis of the fath-1 deficient animals
      revealed a significant reduction in the content of heptadecenoic acid, while
      other major FAs remain unaffected. Feeding of exogenous heptadecenoic acid (C17:
      1), but not oleic acid (C18: 1), rescues the global and subcellular defects of
      fath-1 knockdown worms. CONCLUSION: Our study revealed that FATH-1 and its
      catalytic products are highly specific in the context of chirality, C-chain
      length, spatial distribution, as well as the types of cellular organelles they
      affect. Such an unexpected degree of specificity for the synthesis and functions
      of hydroxylated FAs helps to regulate protein transport and fat metabolism,
      therefore maintaining the cellular homeostasis of the intestinal cells. These
      findings may help our understanding of FA2H functions across species, and offer
      potential therapeutical targets for treating FA2H-related diseases.

PMID- 30184538
TI  - Demographic and Symptomatic Features of Voice Disorders and Their Potential
      Application in Classification Using Machine Learning Algorithms.
AB  - BACKGROUND: Studies have used questionnaires of dysphonic symptoms to screen
      voice disorders. This study investigated whether the differential presentation of
      demographic and symptomatic features can be applied to computerized
      classification. METHODS: We recruited 100 patients with glottic neoplasm, 508
      with phonotraumatic lesions, and 153 with unilateral vocal palsy. Statistical
      analyses revealed significantly different distributions of demographic and
      symptomatic variables. Machine learning algorithms, including decision tree,
      linear discriminant analysis, K-nearest neighbors, support vector machine, and
      artificial neural network, were applied to classify voice disorders. RESULTS: The
      results showed that demographic features were more effective for detecting
      neoplastic and phonotraumatic lesions, whereas symptoms were useful for detecting
      vocal palsy. When combining demographic and symptomatic variables, the artificial
      neural network achieved the highest accuracy of 83 +/- 1.58%, whereas the
      accuracy achieved by other algorithms ranged from 74 to 82.6%. Decision tree
      analyses revealed that sex, age, smoking status, sudden onset of dysphonia, and
      10-item voice handicap index scores were significant characteristics for
      classification. CONCLUSION: This study demonstrated a significant difference in
      demographic and symptomatic features between glottic neoplasm, phonotraumatic
      lesions, and vocal palsy. These features may facilitate automatic classification
      of voice disorders through machine learning algorithms.

PMID- 30184539
TI  - Hypernasal Speech Is Perceived as More Monotonous than Typical Speech.
AB  - BACKGROUND/PURPOSE: Anecdotal clinical reports have stated that hypernasal speech
      sounds monotonous. However, the relationship between the perception of intonation
      (i.e., the fundamental frequency variation across an utterance) and hypernasality
      (excessive nasal resonance during the production of non-nasal sounds) has not
      been investigated in research. We hypothesized that auditory-perceptual ratings
      of intonation would be significantly lower for more hypernasal stimuli. METHODS:
      One male and one female voice actor simulated 3 levels of intonation (monotone,
      normal, and exaggerated) at 4 different levels of hypernasality (normal, mild,
      moderate, and severe). Thirty participants listened to the simulations and rated
      the intonation on a visual analogue scale from 0 (monotone) to 100 (exaggerated).
      RESULTS: A mixed-effects ANOVA revealed main effects of intonation (F2 = 236.46,
      p < 0.001), and hypernasality (F3 = 159.89, p < 0.001), as well as an interaction
      between the two (F6 = 28.35, p < 0.001). Post hoc analyses found that speech was
      rated as more monotonous as hypernasality increased. Summary/Implications: The
      presence of hypernasality in speech can lead listeners to perceive speech as more
      monotonous. Instrumental measures should be used to corroborate auditory
      perceptual evaluations of speech features like intonation.

PMID- 30184540
TI  - Automated Quantification of Fragmented Red Blood Cells: Neonatal Reference
      Intervals and Clinical Disorders of Neonatal Intensive Care Unit Patients with
      High Values.
AB  - BACKGROUND: Schistocytes are circulating erythrocyte fragments. They can be
      identified microscopically from a blood smear; but automated systems evaluate
      more cells and avoid inconsistencies in microscopy. Studies using adult subjects
      indicate that automated quantification of schistocytes can be clinically useful.
      However, reference intervals for automated schistocyte counts of neonates have
      not been published, and the relevance of a high automated schistocyte count from
      neonates has not been reported. OBJECTIVES: Using retrospective automated
      neonatal complete blood count (CBC) data, we created reference intervals for
      fragmented red cells (FRCs) and sought to discover the clinical conditions of
      neonates with high FRCs (above the upper reference interval). RESULTS: We created
      reference intervals based on 39,949 CBCs from 15,655 neonates 0-90 days old. The
      lower reference interval was 0 FRC/uL and the upper interval was 100,000/uL. The
      highest FRCs (96 CBCs from 44 neonates) were > 250,000/uL. These neonates
      clustered into the following groups: 37% had sepsis, 29% had disseminated
      intravascular coagulation (DIC), 17% had a genetic syndrome, 14% necrotizing
      enterocolitis (NEC), and 7% had iron deficiency (some had more than one
      diagnosis). Based on the reference intervals, we divided the 39,949 FRC values
      into 3 groups: (1) < 100,000/uL ("normal"), (2) 100,000-200,000/uL ("moderately
      elevated"), and (3) > 200,000/uL ("extremely elevated"). The odds that a
      microangiopathic condition (DIC, sepsis, NEC) or a microcytic disorder (iron
      deficiency) were present were significantly higher in the moderately elevated,
      and more so in the extremely elevated group. CONCLUSIONS: Our study suggests that
      a high FRC could prompt investigation into, or inform follow-up of, a neonatal
      microangiopathic or extremely microcytic disorder.

PMID- 30184541
TI  - Malignant Narcissism in Relation to Clinical Change in Borderline Personality
      Disorder: An Exploratory Study.
AB  - BACKGROUND: Normal and pathological narcissism have been the focus of
      considerable theoretical discussion and empirical research in recent years in
      personality psychology and psychopathology. Kernberg [<xref ref-type="bibr"
      rid="ref1">1</xref>-<xref ref-type="bibr" rid="ref4">4</xref>] has argued that
      there is a particularly dysfunctional and impairing variant of narcissistic
      disturbance known as malignant narcissism. This exploratory study sought to
      develop, using established assessment methods, a dimensional measure of malignant
      narcissism that incorporates the key features of grandiose narcissism, paranoid
      propensities, psychopathic features, and proclivity for a sadistic and aggressive
      interpersonal style. Method and Sampling: This study examined 57 subjects,
      diagnosed with borderline personality disorder that were treated using 3
      different empirically supported treatments in a previous study [<xref ref
      type="bibr" rid="ref5">5</xref>], for possible deviance on the proposed malignant
      narcissism index. It also evaluated 2 important clinical domains of change in
      relation to malignant narcissism. To wit, it was predicted, based on Kernberg's
      [<xref ref-type="bibr" rid="ref3">3</xref>, <xref ref-type="bibr"
      rid="ref4">4</xref>] clinical model, that elevated levels of malignant narcissism
      would be significantly associated with slower rates of improvement in both
      general psychosocial/psychological functioning and anxiety among treated
      individuals. RESULTS: Higher levels of malignant narcissism were associated, as
      predicted, with slower rates of improvement in both global functioning and
      anxiety. The proposed malignant narcissism index was a more powerful predictor of
      slowed improvement in global functioning than simple narcissistic personality
      disorder features. CONCLUSIONS: The heuristic potential of the malignant
      narcissism construct is discussed and the utility of a dimensional approach to
      this construct is explored, especially in reference employing personality
      traits/processes to better understand pathological configurations and personality
      disturbance.

PMID- 30184542
TI  - miR-338-5p Regulates the Viability, Proliferation, Apoptosis and Migration of
      Rheumatoid Arthritis Fibroblast-Like Synoviocytes by Targeting NFAT5.
AB  - BACKGROUND/AIMS: MicroRNAs (miRNAs) have been reported to be involved in
      Rheumatoid arthritis (RA) pathogenesis and prognosis. However, little is known
      about the disease mechanism in RA. Here, we aim to investigate the potential
      association between miR-338-5p and NFAT5 in RA. METHODS: Aberrant expression of
      miR-338-5p in RA tissues and rheumatoid arthritis fibroblast-like synoviocytes
      (RAFLSs) compared to the normal were determined by RT-qPCR. Cell viability was
      determined using the CCK-8 assay, and cell apoptosis was analyzed via Annexin V
      FITC/PI double staining and was detected using flow cytometry. The targeted
      relationship was determined by TargetScan database and dual luciferase reporter
      gene assay. RESULTS: Upregulation of miR-338-5p facilitated the proliferation,
      migration, invasion and induced G0/G1 arrest of RAFLSs while miR-338-5p inhibitor
      functioned oppositely. Nuclear factor of activated T-cells 5 (NFAT5) was
      confirmed as a downstream target of miR-338-5p which expression was directly
      suppressed by miR-338-5p. Overexpression of NFAT5 attenuated the proliferation
      and metastasis of RAFLSs and those changes could be rescued by co-transfection of
      miR-338-5p. CONCLUSION: miR-338-5p promotes RAFLS's viability and proliferation,
      migration by targeting NFAT5, suggesting a novel therapeutic strategy for RA.

PMID- 30184543
TI  - Maintenance Therapy with Biweekly Cetuximab: Optimizing Schedule Can Preserve
      Activity and Improves Compliance in Advanced Head and Neck Cancer.
AB  - OBJECTIVES: This study evaluates maintenance cetuximab administered every 2 weeks
      (q2w) after chemotherapy plus cetuximab as first-line treatment in a series of
      patients with head and neck squamous cell cancer and compares the results with
      those obtained in a historical control group of patients receiving weekly
      cetuximab. METHODS: After chemotherapy plus cetuximab as first-line treatment, in
      Group A, 36 patients enrolled from October 2016 to November 2017, received
      biweekly cetuximab, administered at 500 mg/m2. Group B was a control group of
      patients treated at our institution from August 2015 to September 2016 and
      received weekly infusion of cetuximab at 250 mg/m2. RESULTS: Confirmed overall
      response rates were, respectively, 19% for Group A and 17% for Group B according
      to intention-to-treat analysis. During the maintenance treatment, median
      progression-free survival (PFS) and median overall survival (OS) were similar for
      both groups (PFS, 4.8 and 4.4 months; OS, 9.0 and 7.9 months; in Groups A and B,
      respectively). The most common adverse events among treated subjects included
      fatigue, rash, and hypomagnesemia. CONCLUSION: Maintenance therapy with
      simplified biweekly cetuximab is a convenient, effective, and well-tolerated
      regimen in patients with recurrent and/or metastatic head and neck squamous cell
      carcinoma.

PMID- 30184544
TI  - Signaling Mechanisms of Myofibroblastic Activation: Outside-in and Inside-Out.
AB  - Myofibroblasts are central mediators of fibrosis. Typically derived from resident
      fibroblasts, myofibroblasts represent a heterogeneous population of cells that
      are principally defined by acquired contractile function and high synthetic
      ability to produce extracellular matrix (ECM). Current literature sheds new light
      on the critical role of ECM signaling coupled with mechanotransduction in driving
      myofibroblastic activation. In particular, transforming growth factor beta1 (TGF
      beta1) and extra domain A containing fibronectin (EDA-FN) are thought to be the
      primary ECM signaling mediators that form and also induce positive feedback
      loops. The outside-in and inside-out signaling circuits are transmitted and
      integrated by TGF-beta receptors and integrins at the cell membrane, ultimately
      perpetuating the abundance and activities of TGF-beta1 and EDA-FN in the ECM. In
      this review, we highlight these conceptual advances in understanding
      myofibroblastic activation, in hope of revealing its therapeutic anti-fibrotic
      implications.

PMID- 30184546
TI  - Decreased Spexin Levels in Patients with Type 1 and Type 2 Diabetes.
AB  - OBJECTIVE: Spexin is a novel peptide which has a potential role as a biomarker of
      insulin resistance, diabetes and obesity. We aimed to measure levels of spexin in
      lean type 1 diabetic patients and its relevance to glycemic parameters without
      the presence of obesity or insulin resistance. SUBJECTS AND METHODS: This cross
      sectional study included 29 type 1 and 30 type 2 diabetic patients and a control
      group of 23 healthy subjects with adjusted age, sex and body mass index (BMI).
      Height and weight were measured using standard techniques. Glucose levels
      triglycerides, total cholesterol, high-density lipoprotein cholesterol, low
      density lipoprotein cholesterol, serum cortisol levels and spexin levels were
      measured for each patient. RESULTS: The median fasting serum spexin levels were
      significantly lower in patients with type 1 and type 2 diabetes than in control
      subjects (p = 0.008, p = 0.041, respectively). Spexin levels were not correlated
      with glycemic parameters, lipids, BMI, cortisol levels and thyroid-stimulating
      hormone (p > 0.05). Only age turned out to be correlated with spexin levels in
      patients with type 1 diabetes when groups are analyzed separately. Regression
      models including age and diabetes duration revealed no association between age
      and spexin levels. Regression models including cortisol, BMI, HbA1c revealed no
      association with spexin levels within each group. CONCLUSION: The presence of
      type 1 diabetes is associated with lower spexin levels, independent of glucose,
      lipid parameters and BMI. The expression of spexin in the pancreas apart from
      current glycemic control of the patients may be the main determinant of spexin
      levels in type 1 diabetic patients.

PMID- 30184545
TI  - Osteopontin Promotes Bone Destruction in Periapical Periodontitis by Activating
      the NF-kappaB Pathway.
AB  - BACKGROUND/AIMS: Periapical periodontitis is caused by bacterial infection and
      results in both one destruction and tooth loss. Osteopontin (OPN) is a secreted
      phosphorylated glycoprotein that participates in bone metabolism. METHODS: Thirty
      three patients with chronic periapical periodontitis and 10 patients who had
      undergone the orthodontic removal of healthy tooth tissue (control) at the
      periodontal ligament were investigated, and an animal model of mouse periapical
      periodontitis was established for an in vivo analysis. The relationship between
      OPN and bone destruction during periapical periodontitis was analyzed.
      Osteoblasts and osteoclasts were cultured in vitro and treated with
      lipopolysaccharide. An inhibitor of NF-kappaB was used to pretreat the
      transfected cells. RESULTS: OPN increased osteoclast proliferation and
      differentiation, but reduced osteoblasts proliferation and differentiation. OPN
      activated the NF-kappaB pathway during periapical periodontitis and accelerated
      the transfer and phosphorylation of P65 from the cytoplasm to the nucleus.
      CONCLUSION: This study demonstrated that OPN played important roles in the
      progression of periapical periodontitis, and a dual role in bone metabolism
      during periapical periodontitis, linking osteoclasts and osteoblasts. The
      underlying mechanism may be related to the NF-kappaB pathway.

PMID- 30184547
TI  - Survival Benefit of Metformin Adjuvant Treatment For Pancreatic Cancer Patients:
      a Systematic Review and Meta-Analysis.
AB  - BACKGROUND/AIMS: Previous studies on the effect of metformin therapy on survival
      of pancreatic cancer patients obtained inconsistent findings. To reevaluate the
      prognostic value of metformin adjuvant treatment, a meta-analysis was carried
      out. METHODS: Relevant articles addressing the association between metformin use
      and pancreatic cancer survival were electronically searched to identify eligible
      studies. Pooled hazard ratios (HRs) and 95% confidence intervals (95% CIs) were
      calculated to assess the strength of the association. RESULTS: Totally, seventeen
      studies involving 36791 participants were included. Overall, metformin use was
      found to be significantly associated with a favorable OS (HR=0.88, 95% CI=0.80
      0.97). Subgroup analyses by ethnicity showed a significantly reduced risk of
      death for metformin users compared with non-users in Asians (HR=0.74, 95% CI=0.58
      0.94) but nonsignificant in Caucasians. When stratified by clinical stage, a
      remarkable reduction of mortality risk in patients at stage I-II treated with
      metformin (HR=0.76, 95% CI=0.68-0.86) was found as well as the group at stage I
      IV (HR=0.88, 95% CI=0.79-0.99), but not in patients at stage III-IV. In the
      stratification analyses based on treatment strategy, metformin therapy was found
      to be associated with a better clinical outcome in patients receiving surgery or
      comprehensive therapy (HR=0.73, 95% CI=0.62-0.87; HR=0.88, 95% CI=0.79-0.97) but
      not chemotherapy. However, the overall analysis failed to show a significant
      association between metformin use and DFS (HR=1.54, 95% CI=0.94 -2.50) with only
      2 studies enrolled. CONCLUSION: The current study has evidenced a significant
      association of metformin adjuvant treatment with the survival benefit for
      pancreatic cancer patients, suggesting a potentially available option for the
      treatment. Further investigation is needed.

PMID- 30184549
TI  - Immunological Dysfunction in Autism Spectrum Disorder: A Potential Target for
      Therapy.
AB  - Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with an
      unknown etiology and currently few effective therapies. Immune system alterations
      have being demonstrated in ASD, both in humans and via animal models; immune
      imbalance thus arises as a possible pathway for drug intervention. In this
      review, the studies were classified into 2 major groups: (1) clinical research
      whose authors classify therapies with primary anti-inflammatory and
      immunomodulatory actions, making use of: sulforaphane, celecoxib, lenalidomide,
      pentoxifylline, spironolactone, flavonoid luteolin, corticosteroids, oral
      immunoglobulin, intravenous immunoglobulin, cell therapy, dialyzable lymphocyte
      extracts, minocycline, and pioglitazone; and (2) other ASD therapies already used
      or currently under study whose initial characteristics were neither anti
      inflammatory nor immunomodulatory initially, but displayed a capacity for
      immunomodulation throughout the treatment: risperidone, vitamin D, omega-3,
      Ginkgo biloba, L-carnosine, N-acetylcysteine, and microbiome restoration. These
      studies used various data acquisition methodologies. Questions arose such the
      need for randomized and placebo-controlled studies with greater numbers of
      participants as well as the use of biomarkers to refine the treatment of autistic
      subjects.

PMID- 30184548
TI  - Exosomal miR-27a Derived from Gastric Cancer Cells Regulates the Transformation
      of Fibroblasts into Cancer-Associated Fibroblasts.
AB  - BACKGROUND/AIMS: The malignant biological behavior of gastric cancer(GC) is not
      only determined by cancer cells alone, but also closely regulated by the
      microenvironment. Fibroblasts represent a large proportion of the components in
      the tumor microenvironment, and they promote the development of disease.
      Currently, accumulating evidence suggests that exosomes can function as
      intercellular transport systems to relay their contents, especially
      microRNAs(miRNAs). METHODS: First, we detected the highly-expressed level of miR
      27a in exosomes isolated from gastric cancer cells by qRT-PCR. MiR-27a -over
      expressed models in vitro and in vivo were established to investigate the
      transformation of cancer-associated fibroblasts observed by Western blotting, and
      the malignant behavior of gastric cancer cells using the methods CCK8 and
      Transwell. Moreover, the downregulation of CSRP2 in fibroblasts was used to
      evaluate the promotion of malignancy of gastric cancer using the methods CCK8 and
      Transwell. RESULTS: In this study, we found a marked high level of miR-27a in
      exosomes derived from GC cells. miR-27a was found to function an oncogene that
      not only induced the reprogramming of fibroblasts into cancer-associated
      fibroblasts(CAFs), but also promoted the proliferation, motility and metastasis
      of cancer cells in vitro and in vivo. Conversely, CAFs with over-expression of
      miR-27a could pleiotropically increase the malignant behavior of the GC cells.
      For the first time, we revealed that CSRP2 is a downstream target of miR-27a.
      CSRP2 downregulation could increase the proliferation and motility of GC cells.
      CONCLUSION: Thus, this report indicates that miR-27a in exosomes derived from GC
      cells has a crucial impact on the microenvironment and may be used as a potential
      therapeutic target in the treatment of GC.

PMID- 30184550
TI  - Is Thicker Choroid a Risk Factor for Malignant Glaucoma?
AB  - PURPOSE: The aim of this study was to evaluate the choroidal thickness (CT) and
      its determinants in primary angle closure glaucoma (PACG) eyes with and without
      malignant glaucoma (MG). METHODS: In this cross-sectional study, we enrolled 25
      patients with bilateral primary angle closure (PAC) diseases; 1 eye of each
      patient was diagnosed with PACG initially and later with MG after trabeculectomy,
      and the fellow eyes were diagnosed with PACG, PAC, or PAC suspect. Thirty-seven
      eyes from 37 PACG patients were recruited as controls. CT was measured at
      different locations (sub-fovea, 1 and 3 mm from the fovea) using spectral-domain
      optical coherence tomography. Comparisons of CT were made among MG, the fellow
      eyes, and the controls. The associations between the determinants and MG were
      analyzed by univariate and multiple logistic regression analysis. RESULTS:
      Macular CT in the eyes with MG was thicker than that of the controls (p < 0.001)
      but not the fellow eyes. Thicker foveal CT was associated with an increased risk
      of MG (odds ratio 1.141). CONCLUSIONS: Thicker foveal CT is an anatomic risk
      factor for MG. The results of our study were consistent with the hypothesis that
      choroidal expansion may play a significant role for the development of MG.

PMID- 30184551
TI  - Cognitive Impairment Along the Course of Depression: Non-Pharmacological
      Treatment Options.
AB  - Major Depressive Disorder (MDD) is one of the most common psychiatric disorders,
      with a large global impact on both the individual and the society. In this
      narrative review, we summarize neurocognitive deficits during acute and
      (partially) remitted states of depression. Furthermore, we outline the potential
      negative effect of cognitive impairment (CI) on functional recovery, and discuss
      the role of several variables in the development of CI for MDD patients. Though
      there is cumulating evidence regarding persistent CI in unipolar depression,
      research on treatment options specific for this patient group is still scarce.
      Hence the central aim of our review is to present non-pharmacological
      interventions, which are thought to reduce CI in affected MDD patients. We
      discuss cognitive remediation therapy (CRT), physical exercise, yoga, mindfulness
      based therapy, and modern neuromodulation approaches like neurostimulation and
      neurofeedback training. In conclusion, we propose future directions for research
      on CI in depression. Looking further ahead, we suggest creative interventional
      designs that include a direct comparison of different non-pharmacological
      treatment approaches on neurocognition and functional outcome of MDD.
      Furthermore, additive and synergistic effects of CRT with other treatment
      approaches should be examined and compared to create multimodal and even
      personalized intervention programs.

PMID- 30184552
TI  - Telemedical Deep Brain Stimulation: Merits and Limitations.

PMID- 30184554
TI  - [Induction of Labour in Nulliparous Women Beyond Term in a Low-Risk Population].
AB  - PURPOSE: To evaluate the influence of gestational age on induction of labour in
      nulliparous women. MATERIAL AND METHODS: This historical cohort study analyzed
      inductions of labour in low-risk nulliparous women. Therefore the collective was
      divided into 3 groups (group 1: 40+0 to 40+6 weeks of gestation, group 2: 41+0 to
      41+3 weeks of gestation, group 3:>41+3 weeks of gestation). The primary outcome
      measure was the caesarean section rate. RESULTS: The caesarean section rate was
      not different among the 3 groups (p=0.4036). The impact of gestational age on
      induction in multivariable analysis was not significant. Maternal BMI (p<0.0001),
      maternal age (p=0.0005) and birth weight (p=0.0151) had an influence on the
      caesarean section rate. Regarding the secondary outcome measures such as
      umbilical cord blood pH, Apgar score and postpartal neonatal intensive care unit
      admission, no statistically significant differences have been revealed among the
      groups. CONCLUSION: Timing of labour induction after 40+0 weeks of gestation in a
      low-risk population of nulliparous women did not influence the caesarean section
      rate.

PMID- 30184553
TI  - Effect of Combined Treatment with MLC601 (NeuroAiDTM) and Rehabilitation on Post
      Stroke Recovery: The CHIMES and CHIMES-E Studies.
AB  - BACKGROUND AND PURPOSE: MLC601 has been shown in preclinical studies to enhance
      neurorestorative mechanisms after stroke. The aim of this post hoc analysis was
      to assess whether combining MLC601 and rehabilitation has an effect on improving
      functional outcomes after stroke. METHODS: Data from the CHInese Medicine
      NeuroAiD Efficacy on Stroke (CHIMES) and CHIMES-Extension (CHIMES-E) studies were
      analyzed. CHIMES-E was a 24-month follow-up study of subjects included in CHIMES,
      a multi-centre, double-blind placebo-controlled trial which randomized subjects
      with acute ischemic stroke, to either MLC601 or placebo for 3 months in addition
      to standard stroke treatment and rehabilitation. Subjects were stratified
      according to whether they received or did not receive persistent rehabilitation
      up to month (M)3 (non- randomized allocation) and by treatment group. The
      modified Rankin Scale (mRS) and Barthel Index were assessed at month (M) 3, M6,
      M12, M18, and M24. RESULTS: Of 880 subjects in CHIMES-E, data on rehabilitation
      at M3 were available in 807 (91.7%, mean age 61.8 +/- 11.3 years, 36% female).
      After adjusting for prognostic factors of poor outcome (age, sex, pre-stroke mRS,
      baseline National Institute of Health Stroke Scale, and stroke onset-to-study
      treatment time), subjects who received persistent rehabilitation showed
      consistently higher treatment effect in favor of MLC601 for all time points on
      mRS 0-1 dichotomy analysis (ORs 1.85 at M3, 2.18 at M6, 2.42 at M12, 1.94 at M18,
      1.87 at M24), mRS ordinal analysis (ORs 1.37 at M3, 1.40 at M6, 1.53 at M12, 1.50
      at M18, 1.38 at M24), and BI >=95 dichotomy analysis (ORs 1.39 at M3, 1.95 at M6,
      1.56 at M12, 1.56 at M18, 1.46 at M24) compared to those who did not receive
      persistent rehabilitation. CONCLUSIONS: More subjects on MLC601 improved to
      functional independence compared to placebo among subjects receiving persistent
      rehabilitation up to M3. The larger treatment effect of MLC601 was sustained over
      2 years which supports the hypothesis that MLC601 combined with rehabilitation
      might have beneficial and sustained effects on neuro-repair processes after
      stroke. There is a need for more data on the effect of combining rehabilitation
      programs with stroke recovery treatments.

PMID- 30184555
TI  - [Minimal-invasive Cochlear Implantation: Surgical feasibility and first clinical
      experience].
AB  - OBJECTIVE: Cochlear implantation is a standard procedure for rehabilitation of
      profound hearing loss and single sided deafness. Audiologic criteria for
      implantation have been extended with the growing experience. Less traumatic
      access has been developed at the same time. METHODS AND PATIENTS: This study
      reports first experiences with a minimaltraumatic cochlear implantation (MiCI)
      approach in a series of 31 consecutive patients (9-79 yrs.) in our department.
      The approach combines a short retroauricular incision of 25mm with a minimized
      mastoidectomy, a round window approach and a temporal well for the implant.
      RESULTS: Retroauricular incision could be reduced to 29, 7 mm, the size of the
      mastoid cavity to 20 mm2 and the stay in hospital for 0,55 days in average. Main
      postoperative complaint was dizziness. Overall complication rate was comparable
      to conventional surgery. CONCLUSION: Minimal-invasive cochlear implantation is a
      safe and reliable procedure in experienced hands for children and adults.

PMID- 30184556
TI  - Maternal Obesity Affects Cardiac Remodeling and Recovery in Women with Peripartum
      Cardiomyopathy.
AB  - OBJECTIVE:  To examine the association between maternal obesity on left
      ventricular (LV) size and recovery in women with peripartum cardiomyopathy
      (PPCM). STUDY DESIGN:  This was a prospective analysis of 100 women enrolled
      within 13 weeks of PPCM diagnosis and followed for a year in the Investigation of
      Pregnancy Associated Cardiomyopathy study. Adiposity was defined by standard body
      mass index (BMI) definitions for under/normal weight, overweight, and obesity.
      Demographic, clinical, and biomarker variables were compared across weight
      categories. OUTCOMES:  LV end-diastolic diameter (LVEDD) and ejection fraction
      were measured at entry, 6, and 12 months postpartum. Multivariable regression
      models examined the relationship between adiposity, LV size, and leptin levels
      with cardiac recovery at 6 and 12 months postpartum. RESULTS:  Obese and nonobese
      women had similar LV dysfunction at entry. Obese women had greater LV size and
      less LV recovery at 6 and 12 months postpartum. BMI was positively associated
      with leptin and ventricular diameter. Greater BMI at entry remained associated
      with less ventricular recovery at 6 months (p = 0.02) in adjusted race-stratified
      models. LVEDD at entry predicted lower ejection fraction at 6 months (p < 0.001)
      and similarly at 12 months. CONCLUSION:  Obese women with PPCM had greater
      cardiac remodeling, higher leptin levels, and diminished cardiac recovery.

PMID- 30184557
TI  - Occult Placenta Accreta: Risk Factors, Adverse Obstetrical Outcomes, and
      Recurrence in Subsequent Pregnancies.
AB  - OBJECTIVE:  To assess the risk factors, adverse obstetrical outcomes, and
      recurrence risk associated with pathologically diagnosed occult placenta accreta.
      METHODS:  This was a retrospective observational study of clinically adherent
      placentas requiring manual extraction that underwent pathological examination.
      Cases were defined as those with histological evidence of placenta accreta, and
      controls were defined as those without accreta. All subsequent pregnancies were
      evaluated to determine the recurrence risk of occult accreta in future
      pregnancies. RESULTS:  Of 491 women with clinically adherent placentas, 100
      (20.1%) with a pathological diagnosis of occult accreta were compared with 391
      (79.9%) without occult accreta. In bivariable analysis, risk factors associated
      with occult accreta included a history of previous cesarean (19 vs. 10.7%; p =
      0.03) and prior uterine surgery (35 vs. 19.7%; p = 0.001). Adverse obstetrical
      outcomes were more common in women with occult accreta including postpartum
      hemorrhage (59 vs. 31.7%; p < 0.001) and peripartum hysterectomy (21 vs. 0.3%; p
      < 0.001). In 130 subsequent pregnancies, there was an increased risk of retained
      placenta (42.9 vs. 19%; p = 0.04) and recurrence of occult accreta (29.6 vs.
      6.8%; p = 0.05). CONCLUSION:  Occult accreta is associated with an increased risk
      of hemorrhagic morbidity and recurrence of morbidly adherent placenta in
      subsequent pregnancies.

PMID- 30184558
TI  - Chlorhexidine-Alcohol Compared with Povidone-Iodine Preoperative Skin Antisepsis
      for Cesarean Delivery: A Systematic Review and Meta-Analysis.
AB  - OBJECTIVE:  To compare chlorhexidine-alcohol with povidone-iodine solutions for
      skin antisepsis prior to cesarean delivery for the prevention of surgical site
      infection. STUDY DESIGN:  Electronic databases MEDLINE, Embase, Scopus, and
      Clinicaltrials.gov were searched from inception to August 2017. Eligible studies
      included randomized controlled trials comparing chlorhexidine-alcohol with
      povidone-iodine skin preparation solutions for women undergoing cesarean
      delivery. The primary outcome was surgical site infection including superficial
      or deep wound infection. Meta-analysis was performed, and risk ratios (RRs) with
      95% confidence interval (CI) were calculated using the Mantel-Haenszel random
      effects model. Statistical heterogeneity was assessed using Higgin's I2. RESULTS:
      Of 61 abstracts identified in the primary search, four studies (3,059 women) met
      the eligibility criteria. The risk of surgical site infection was significantly
      reduced with chlorhexidine-alcohol (RR: 0.72; 95% CI: 0.52-0.98). No
      heterogeneity across studies was observed with I2 = 0%. Subgroup analysis of
      superficial infection only or deep infection only showed no statistically
      significant difference (RR: 0.76, 95% CI: 0.54-1.08; and RR: 0.50, 95% CI: 0.23
      1.10, respectively). CONCLUSION:  Preoperative skin cleansing prior to cesarean
      delivery with chlorhexidine-alcohol reduces surgical site infection as compared
      with povidone-iodine solutions.

PMID- 30184559
TI  - Applying the RE-AIM Framework for the Evaluation of a Clinical Decision Support
      Tool for Pediatric Head Trauma: A Mixed-Methods Study.
AB  - BACKGROUND:  The overuse of cranial computed tomography (CT) to diagnose
      potential traumatic brain injuries (TBIs) exposes children with minor blunt head
      trauma to unnecessary ionizing radiation. The Pediatric Emergency Care Applied
      Research Network and the Clinical Research on Emergency Services and Treatments
      Network implemented TBI prediction rules via electronic health record (EHR)
      clinical decision support (CDS) to decrease use of CTs in children with minor
      blunt head trauma. OBJECTIVE:  This article aims to facilitate implementation and
      dissemination of a CDS alert into emergency departments around the country.
      METHODS:  We evaluated the EHR CT CDS tool through a mixed-methods analysis of 38
      audio-recorded interviews with health care stakeholders and quantitative data
      sources, using the Reach, Efficacy, Adoption, Implementation, and Maintenance
      framework. RESULTS:  Reach -: The demographics of participants enrolled in the
      clinical trial were consistent with national estimates of TBI prevalence.
      Efficacy-There was a variable and modest reduction in CT rates for the 8,067
      children with minor head trauma whose clinicians received CDS. Adoption -: The
      EHR CT CDS tool was well matched with the organizational mission, values, and
      priorities of the implementation sites. Implementation- The most important
      predisposing factors for successful implementation were the presence of an
      approachable clinical champion at each site and belief that the tool was a
      relevant, reusable knowledge asset. Enabling factors included an effective
      integration within the clinical workflow, organizational investment in user
      training, and ease of use. Maintenance -: Reinforcing factors for the EHR CT CDS
      tool included a close fit with the institutional culture, belief that it was
      useful for providers and families, and a good educational and informational tool.
      As such, the EHR CT CDS tool was maintained in clinical practice long after study
      completion. CONCLUSION:  Data from this mixed-methods study complement findings
      from the efficacy trial and provide critical components for consideration prior
      to integration and subsequent dissemination of the EHR CT CDS tool. TRIAL
      REGISTRATION:  NCT01453621, Registered September 27, 2011.

PMID- 30184560
TI  - A Brief Survey on Six Basic and Reduced eHealth Indicators in Seven Countries in
      2017.
AB  - BACKGROUND:  Holistic, ubiquitous support of patient-centered health care
      (eHealth) at all health care institutions and in patients' homes through
      information processing is increasingly supplementing institution-centered care.
      While eHealth indicators may measure the transition from institution-centered
      (e.g., hospital-centered) information processing to patient-centered information
      processing, collecting relevant and timely data for such indicators has been
      difficult. OBJECTIVES:  This article aims to design some basic eHealth
      indicators, which are easily collected and measure how well information
      processing supports holistic patient-centered health care, and to evaluate
      penetrance of patient-centered health as measured by the indicators
      internationally via an expert survey. METHODS:  We identified six basic
      indicators that measure access of health care professionals, patients, and
      caregivers to the patient's health record data and the ability of providers,
      patients, and caregivers to add information in the patient's record. In a survey
      of international informatics experts, these indicators' penetrance were evaluated
      for Austria, Finland, Germany, Hong Kong, South Korea, Sweden, and the United
      States in the summer of 2017. RESULTS:  The eHealth status measured by the
      indicators varied significantly between these seven countries. In Finland, most
      practices measured by the indicators were fully implemented whereas in Germany
      only one practice was partially realized. CONCLUSION:  Progress in the
      implementation of practices that support patient-centered care could mainly be
      observed in those countries where the "political will" focused on achieving
      patient-centered care as opposed to an emphasis on institution-centered care. The
      six eHealth indicators seem to be useful for measuring national progress in
      patient-centered care. Future work will extend the number of countries analyzed.

PMID- 30184561
TI  - Determinants of Visfatin/NAMPT Serum Concentration and its Leukocyte Expression
      in Hyperthyroidism.
AB  - We aimed to analyze the potential influence of thyroid autoimmunity on
      visfatin/NAMPT serum concentration and its leukocyte expression in hyperthyroid
      patients. This is a single-center, cross-sectional study with consecutive
      enrollment. All patients with newly diagnosed overt hyperthyroidism in a course
      of Graves' disease or toxic nodular goiter were included in the study. They
      underwent physical examination, laboratory investigation, body composition
      analysis, and thyroid ultrasound. NAMPT mRNA leukocyte expressions were measured
      using RT-qPCR. Of the 173 patients, 95 were enrolled in further analysis [67
      patients with Graves' disease (GD) and 28 with toxic nodular goiter (TNG)].
      Control group consisted of 43 healthy volunteers adjusted for age, sex, and BMI.
      Higher NAMPT/visfatin serum concentration was found in patients with GD comparing
      with patients with TNG (p=0.03855). We found significant NAMPT leukocyte
      overexpression in GD patients (n=32) as compared to TNG patients (n=18) and
      euthyroid controls (n=24) (p=0.005965). Simple linear regression analysis
      revealed that NAMPT/visfatin serum concentration was significantly associated
      with NAMPT leukocyte expression, thyroid autoimmunity, age, HOMA-IR, and fat mass
      percentage (FM%). NAMPT leukocyte expression was related to thyroid autoimmunity,
      age, and TRAb levels. The stepwise multiple regression analysis revealed FM% and
      HOMA-IR as independent predictors of visfatin/NAMPT serum levels. In a separate
      stepwise multiple regression analysis, we confirmed the association between NAMPT
      leukocyte expression and TRAb levels. We found that fat mass percentage together
      with HOMA-IR are the most significant predictors of visfatin/NAMPT serum
      elevation in hyperthyroid patients.

PMID- 30184563
TI  - Panhypopituitarism Without GH Replacement: About Insulin Sensitivity, CRP Levels,
      and Metabolic Syndrome.
AB  - A complete deficiency of anterior pituitary hormones from several etiologies
      characterizes Panhypopituitarism (PH). Despite advances in treatment, patients
      with PH maintain high rates of morbidity and mortality, a reason to investigate
      some insulin sensitivity, metabolic and inflammatory parameters that could be
      related to the increase of these indicators. This was a cross-sectional study
      comprising 41 PH patients under hormonal replacement, except for growth hormone,
      and 37 individuals in a control group (CG) with similar age, gender and body mass
      index (BMI). We assessed clinical data as age, sex, BMI, waist circumference,
      waist/hip ratio (WHR), history of hypertension, diabetes mellitus and
      dyslipidemia as well as fasting glycaemia, insulin, HOMA-IR, HbA1c, high
      sensitivity CRP (hs-CRP), and lipid profile. PH patients presents lower values of
      glycaemia, insulin, HOMA-IR (0.88 vs 2.1) and WHR, but higher levels of hs-CRP
      (0.38 vs 0.16mg/dl) when compared with the CG. Although the occurrence of
      dyslipidemia was higher in patients with PH, the frequency of metabolic syndrome
      was similar between the groups. In multivariate linear regression analysis, the
      PH group independently predicted lower HOMA-IR and WHR values. In conclusion,
      this study demonstrated that patients with PH without GH replacement have lower
      HOMA-IR and WHR values and higher levels of hs-CRP than a CG paired by age,
      gender and BMI. The diagnosis of dyslipidemia was more frequent in patients with
      PH, but the occurrence of MS was similar to CG. Further studies are needed to
      confirm our findings and to better understand the metabolic characteristics of
      patients with PH.

PMID- 30184562
TI  - MetS Risk Score: A Clear Scoring Model to Predict a 3-Year Risk for Metabolic
      Syndrome.
AB  - Although several risk factors for metabolic syndrome (MetS) have been reported,
      there are few clinical scores that predict its incidence. Therefore, we created
      and validated a risk score for prediction of 3-year risk for MetS. Three-year
      follow-up data of 4395 initially MetS-free subjects, enrolled for an annual
      physical examination from Wenzhou Medical Center were analyzed. Subjects at
      enrollment were randomly divided into the training and the validation cohort.
      Univariate and multivariate logistic regression models were employed for model
      development. The selected variables were assigned an integer or half-integer risk
      score proportional to the estimated coefficient from the logistic model. Risk
      scores were tested in a validation cohort. The predictive performance of the
      model was tested by computing the area under the receiver operating
      characteristic curve (AUROC). Four independent predictors were chosen to
      construct the MetS risk score, including BMI (HR=1.906, 95% CI: 1.040-1.155), FPG
      (HR=1.507, 95% CI: 1.305-1.741), DBP (HR=1.061, 95% CI: 1.002-1.031), HDL-C
      (HR=0.539, 95% CI: 0.303-0.959). The model was created as -1.5 to 4 points, which
      demonstrated a considerable discrimination both in the training cohort
      (AUROC=0.674) and validation cohort (AUROC=0.690). Comparison of the observed
      with the estimated incidence of MetS revealed satisfactory precision. We
      developed and validated the MetS risk score with 4 risk factors to predict 3-year
      risk of MetS, useful for assessing the individual risk for MetS in medical
      practice.

PMID- 30184564
TI  - ?

PMID- 30184565
TI  - ?

PMID- 30184566
TI  - ?

PMID- 30184567
TI  - ?

PMID- 30184569
TI  - ?

PMID- 30184568
TI  - ?

PMID- 30184570
TI  - ?

PMID- 30184573
TI  - [Lung Transplantation. Chances and Possibilities].
AB  - Since 1963, the lung transplantation has become a successful and established
      therapy for patients with lung failure. Even though mortality is higher than with
      other solid organ transplantations, remarkable progress has been made due to
      improved techniques, improved conservation, immunosuppression and antibiotics as
      well as diagnostic tools and therapy for rejection. The survival for lung
      transplantation is good. The survival rate after 3 months is 88%, after 1 year
      79% and after 3, 5, and 10 years 64%, 53%, and 31%, respectively. But chronic
      rejection, presenting as chronic lung allograft dysfunction, is still a major
      problem after lung transplantation. An overview of indications and
      contraindications, surgical techniques and results is given in this article.

PMID- 30184574
TI  - [Editor's Comment].

PMID- 30184571
TI  - [Treatment of Sternal Osteomyelitis after Median Sternotomy in 130 Patients with
      Pedicled Myocutaneous Latissimus Flap].
AB  - BACKGROUND: After median sternotomy in cardiac surgery, deep sternal wound
      infections develop in 0.8 - 8% of patients, resulting in prolonged hospital stay
      and increased morbidity and mortality. Our treatment strategy combines radical
      surgical debridement, removal of extraneous material and reconstruction of large
      and deep defects by a pedicled M. latissimus dorsi flap. With retrospective
      analysis of patient characteristics and pre- und perioperative data we could
      identify risk factors in regard to proper wound healing and bleeding
      complications. MATERIAL AND METHODS: Patient characteristics (age, BMI, gender),
      medical history (diabetes mellitus, chronic obstructive lung disease, renal
      insufficiency and pre- and perioperative data (anticoagulation, bacterial
      colonization during reconstruction) were collected for 130 patients treated by
      latissimus flap to cover sternal wounds between 2009 and 2015. RESULTS: The mean
      age was 68.72 +/- 9.53 years; 37% of patients were female. The in-hospital
      mortality was 3.8%. Reoperation rate because of wound healing problems was 21.5%;
      bleeding complications leading to reoperation occurred in 10.8% of all patients.
      At the point of reconstruction, Staphylococcus (S.) aureus and S. epidermidis
      were detected most frequently. Age over 80 (p = 0.04), female sex (p = 0.002),
      detection of fecal bacteria (p = 0.006), or multiresistant bacteria (p = 0.007)
      and Klebsiellae were regarded as significant risk factors for wound healing
      problems leading to reoperation after flap surgery. High dose therapy with
      danaparoid/fondaparinux was a significant risk factor for bleeding complications
      needing reoperation. CONCLUSION: The pedicled latissimus flap has to be
      considered as the preferred method in large sternal wounds to achieve sufficient
      defect filling. The risk of wound healing disruption is significantly influenced
      by bacteria detected in the sternal wound at the point of reconstructive surgery.

PMID- 30184575
TI  - ?

PMID- 30184576
TI  - ?

PMID- 30184577
TI  - ?

PMID- 30184578
TI  - [Diagnostics of allergies with prick test].

PMID- 30184579
TI  - [Stents and spacers in endoscopic endonasal sinus surgery].
AB  - In endonasal endoscopic sinus surgery continuous progress has been made in the
      last decade due to better understanding of microanatomy, gains in adjunctive
      medicative therapy and technical innovations. Moreover, continuous research and
      clinical trials on innovative stents and spacers with and without defined drug
      eluting features may be mentioned in this context. A narrative review of the
      current development status and its therapeutic options referring to the latter is
      presented.

PMID- 30184580
TI  - [From the Expert's Office: Overdose of a topical alpha-sympathomimetic drug - a
      medical malpractice].

PMID- 30184582
TI  - ?

PMID- 30184581
TI  - ?

PMID- 30184583
TI  - ?

PMID- 30184584
TI  - ?

PMID- 30184585
TI  - ?

PMID- 30184586
TI  - ?

PMID- 30184587
TI  - ?

PMID- 30184589
TI  - ?

PMID- 30184588
TI  - ?

PMID- 30184590
TI  - ?

PMID- 30184591
TI  - ?

PMID- 30184592
TI  - ?

PMID- 30184593
TI  - ?

PMID- 30184594
TI  - ?

PMID- 30184595
TI  - ?

PMID- 30184596
TI  - ?

PMID- 30184597
TI  - ?

PMID- 30184598
TI  - [The significance of palliative surgery in castration-resistant prostate cancer].
AB  - If prostate cancer recurs after primary treatment, deprivation therapy with LHRH
      analogues or antagonists is the treatment of choice in men with metastatic
      prostate cancer. However, this treatment only achieves palliative results. Median
      time to progression ranges between 11 and 78 months. After the introduction of
      Docetaxel as a first-line treatment in castration-resistant prostate cancer
      (CRPCA) and cabazitaxel as a second-line chemotherapy, several new drugs
      containing abiraterone, enzalutamide, radium 223 and sipuleucel-T have become
      available, which can lead to complete or partial remissions in metastasis, but do
      not have an effect on the prostate itself as has been shown recently. As a result
      of local progression of CRPCA, local complications of the urinary tract such as
      subvesical obstruction, recurrent gross haematuria with or without clotting,
      upper urinary tract dilatation, rectourethral or rectovesical fistulae and rectal
      obstruction will occur in about one third of all patients. Several surgical
      treatment options are available to manage the aforementioned complications. In
      patients with local progressive CRPCA and lower urinary tract symptoms,
      palliative TUR-P, radical prostatectomy or radical cystoprostatectomy with
      urinary diversion and even anterior and posterior exenteration can be performed
      in selected patients, requiring a preoperative multiparametric MRI of the
      prostate and the pelvic floor along with a laboratory examination to optimise
      surgical techniques and perioperative outcomes. In case of symptomatic
      involvement of the upper urinary tract system, the placement of endoluminal DJ
      stents or percutaneous nephrostomy in men with a poor performance status and a
      short life expectancy is the treatment of choice. In men with an ECOG performance
      status of 0 to 1, reconstructive surgery such as ureteral reimplantation, ileal
      ureteral replacement or placement of a subcutaneous pyelovesical bypass is an
      appropriate treatment option. To summarise, the aforementioned palliative
      surgical treatment options should be provided for selected patients and performed
      by well-experienced urologists.

PMID- 30184599
TI  - [Palliative surgery for metastatic urothelial cancer].
AB  - Palliative surgery is performed in order to relieve symptoms as well as to
      increase survival in selected tumour entities. For urothelial cancer, its role is
      limited and clinical data are limited, too. Yet with better responses being
      achieved to systemic therapy, more and more surgical procedures are being carried
      out in the form of individualised treatment concepts and are then published as
      case series. For patients with low metastatic load, or if the tumour is
      restricted to lymph nodes inside and outside the pelvis, as well as for singular
      pulmonary metastasis, there seems to be a survival benefit in select cases.
      Calculation of risks and benefits is difficult and, for now, should be
      reconsidered for every individual patient. Therefore, prospective trials are
      difficult to perform and should not be expected to exist in the future. This
      review aims to summarise the most important publications on this topic.

PMID- 30184600
TI  - [Symptomatic renal tumours in metastatic renal cell carcinoma - surgical
      options].
AB  - Between 15 and 20 % of patients diagnosed with renal cell carcinoma suffer from
      metastatic disease by the time of diagnosis. In addition to systemic therapy,
      there are various surgical strategies to treat the primary tumour, e. g.
      cytoreductive nephrectomy (CN) or palliative nephrectomy (PN). In the
      immunotherapy era, the standard treatment was to perform CN followed by
      interferon therapy, based on 2 prospective randomised trials and their combined
      analysis. Since the introduction of targeted therapy around 2005, data of that
      quality has been missing and clinicians have had to rely on big retrospective
      studies, which have confirmed the benefit of CN except for patients with low
      performance status, cerebral metastases, low life expectancy, and old age. The
      recently published results of the CARMENA trial, which compared the use of
      sunitinib versus CN followed by sunitinib in a prospective randomised trial, have
      now demonstrated non-inferiority of sunitinib alone in patients classified as
      having intermediate-risk or poor-risk disease. Nevertheless, these results remain
      debatable given the large number of patients with poor-risk disease and a higher
      percentage of locally advanced tumours in the nephrectomy-sunitinib group.
      Indications for palliative nephrectomy are pain, haemorrhage, or severe
      paraneoplastic syndrome. Since there are excellent supportive and less invasive
      therapies, e. g. angioembolisation in case of haemorrhage, the decision in favour
      of surgical intervention should be based on the characteristics of the primary
      tumour, individual risk factors, and alternative therapies. Technically,
      palliative nephrectomy can be performed as an open or laparoscopic procedure and
      even as a partial nephrectomy, if indicated.

PMID- 30184601
TI  - [Symptomatic urinary obstruction in patients with metastatic malignancies].
AB  - Symptomatic urinary obstruction, characterised by decreased or absent urinary
      outflow, is a common concomitant disease in patients with urological malignancies
      or carcinomas forming abdominal metastases. While acute urinary obstruction is
      associated with renal colics, chronic urinary obstruction often goes unnoticed
      for a long time. In addition to intrinsic causes such as upper urinary tract
      tumours, this condition is often caused by external compression of the ureter by
      tumour masses. Placement of a ureteral JJ stent or a percutaneous nephrostomy
      tube results in early disobstruction. Depending on the prognosis of the
      underlying disease, a definitive surgical restoration may be considered.

PMID- 30184602
TI  - ?

PMID- 30184603
TI  - ?

PMID- 30184604
TI  - ?

PMID- 30184605
TI  - Correction: Clinical utility of novel ultrathin single-balloon enteroscopy: a
      feasibility study.

PMID- 30184606
TI  - Double lumen esophagus due to false submucosal path induced by nasogastric tube:
      endoscopic treatment with marsupialization.

PMID- 30184607
TI  - Endoscopic sleeve gastroplasty using the novel Endomina device for morbidly obese
      patients.

PMID- 30184608
TI  - Screening of esophageal varices in children using esophageal capsule endoscopy: a
      multicenter prospective study.
AB  - BACKGROUND:  Esophagogastroduodenoscopy (EGD) is the standard method for
      diagnosis of esophageal and gastric varices in children. In this prospective
      study we evaluated the use of PillCam esophageal capsule endoscopy (ECE) in
      pediatric patients. METHODS:  Patients aged 7 to 18 years presenting with portal
      hypertension and/or cirrhosis underwent ECE (PillCam ESO 2, Given Imaging Ltd.)
      followed by EGD. RESULTS:  102 patients were screened, 81 (52 boys; mean age
      13.96 +/- 0.25 years) were included and 21 were excluded (16 for "candy test"
      failure). Esophageal varices were identified by EGD in 62 patients (77 %) and by
      ECE in 57 patients (70 %) using the de Franchis classification (DFC). The
      sensitivity of ECE for esophageal varices was 92 % and the specificity was 100 %
      using DFC. Based upon 57/81 patients with small, medium, and large varices on
      both ECE and EGD, using DFC, the sensitivity, specificity, positive (PPV) and
      negative predictive value (NPV) were 55 %, 92 %, 89 %, and 63 %, respectively,
      giving a total overall accuracy of 72 %. To improve sensitivity and specificity
      in classification of esophageal varices, we propose using a modified score. This
      score detected esophageal varices with 100 % sensitivity, 93 % specificity, 94 %
      PPV, and 100 % NPV, giving a total overall accuracy of 97 %. All patients
      preferred ECE over EGD. No capsule retention was recorded. CONCLUSIONS:  ECE is a
      well-tolerated and safe procedure in children. Using the modified score, the
      sensitivity of ECE is currently sufficient to detect esophageal varices and
      replace EGD in infants with suspicion of esophageal varices or when EGD is
      refused.

PMID- 30184609
TI  - Tissue acquisition for diagnosis of biliary strictures using peroral
      cholangioscopy or endoscopic ultrasound-guided fine-needle aspiration.
AB  - BACKGROUND:  Although endoscopic retrograde cholangiopancreatography (ERCP) is a
      first-line diagnostic modality for suspected malignant biliary stricture (MBS),
      the diagnostic yield of ERCP-based tissue sampling is insufficient. Peroral
      cholangioscopy-guided forceps biopsy (POC-FB) and endoscopic ultrasound-guided
      fine-needle aspiration biopsy (EUS-FNAB) are evolving as reliable diagnostic
      procedures for inconclusive MBS. This study aimed to evaluate the usefulness of a
      diagnostic approach using POC-FB or EUS-FNAB according to the stricture location
      in patients with suspected MBS. METHODS:  Consecutive patients diagnosed with
      suspected MBS with obstructive jaundice and/or cholangitis were enrolled
      prospectively. ERCP with transpapillary forceps biopsy (TPB) was performed
      initially. When malignancy was not confirmed by TPB, POC-FB using a SpyGlass
      direct visualization system or direct POC using an ultraslim endoscope was
      performed for proximal strictures, and EUS-FNAB was performed for distal
      strictures as a follow-up biopsy. RESULTS:  Among a total of 181 patients,
      initial TPB showed malignancy in 122 patients, and the diagnostic accuracy of
      initial TPB was 71.8 % (95 % confidence interval [CI] 65.3 % - 78.4 %]. Of the 59
      patients in whom TPB was negative for malignancy, 32 had proximal biliary
      strictures and underwent successful POC. The remaining 27 patients had distal
      strictures and underwent successful EUS-FNAB. The accuracy of malignancy
      detection using POC-FB for proximal biliary strictures and EUS-FNAB for distal
      biliary strictures was 93.6 % (95 %CI 84.9 %-100 %) and 96.3 % (95 %CI 89.2 %-100
      %), respectively. The overall diagnostic accuracy for the combination of TPB with
      either POC-FB for proximal strictures and EUS-FNAB for distal strictures was 98.3
      % (95 %CI 95.9 %-100 %) and 98.4 % (95 %CI 95.3 %-100 %), respectively.
      CONCLUSIONS:  An approach using POC-FB or EUS-FNAB according to the stricture
      location may be useful in the diagnosis of suspected MBS.

PMID- 30184610
TI  - The effect of photo-documentation of the ampulla on neoplasm detection rate
      during esophagogastroduodenoscopy.
AB  - BACKGROUND:  A few studies have investigated quality indicators of
      esophagogastroduodenoscopy (EGD) for identifying upper gastrointestinal (GI)
      malignancy. The current study aimed to evaluate whether the rate of ampulla photo
      documentation could be associated with the detection of upper GI neoplasms.
      METHODS:  We used data from 111 962 asymptomatic patients who underwent EGD
      performed by 14 endoscopists at a health promotion center. The rate of ampulla
      photo-documentation was calculated by reviewing EGD photos archived during each
      endoscopist's first year of working at the center. The detection of neoplasms
      during a 7-year period was investigated. We examined the association between the
      rate of ampulla photo-documentation and the rate of neoplasm detection. RESULTS: 
      The mean rate of ampulla photo-documentation was 49.0 % (range 13.7 % - 78.1 %)
      during endoscopists' first year of working at the center. Endoscopists' rates of
      ampulla photo-documentation significantly correlated with the detection of total
      neoplasms (R2 = 0.57, P = 0.03) and small neoplasms (R2 = 0.58, P = 0.03). There
      was a significant difference in the detection rates of upper GI neoplasms between
      high (n = 7) and low (n = 7) ampulla observers (odds ratio [OR] 1.31, 95 %
      confidence interval [CI] 1.03 - 1.68; P = 0.03). The ampulla photo-documentation
      rate of each endoscopist significantly correlated with the examination time for a
      normal EGD (R2 = 0.55; P = 0.04). In multivariate analysis, high ampulla photo
      documentation rate was a predictor of neoplasm detection (OR 1.33, 95 %CI 1.03 -
      1.70). CONCLUSIONS:  The ampulla photo-documentation rate was significantly
      associated with the detection rate for both total and small upper GI neoplasms.
      Ampulla photo-documentation should be considered as a quality indicator of EGD.

PMID- 30184611
TI  - Is community social capital associated with subjective symptoms of dementia among
      older people? A cross-sectional study in Japan.
AB  - AIM: Many studies have reported the preventive effects of community social
      capital on health outcomes, such as mortality and incidence of diseases. However,
      evidence on the association between community social capital and dementia-related
      outcomes remains sparse. The present study examined the contextual association of
      social capital with subjective symptoms of dementia among community-dwelling
      older adults in Japan, using a population-based, large-scale questionnaire
      survey. METHODS: Data were used from a cross-sectional survey for all community
      dwelling individuals aged >=65 years in Adachi Ward, Tokyo (n = 132 005).
      Subjective dementia symptoms were assessed using a self-administered dementia
      checklist, which was validated by the Clinical Dementia Rating Scale. Social
      capital was assessed by neighborhood cohesion (neighborhood trust, neighborhood
      attachment and sense of belonging to the neighborhood) and neighborhood network
      (i.e. social relationships with neighbors). Individual responses from each
      district were aggregated to create indicators of district-level social capital.
      RESULTS: A total of 75 338 questionnaires were analyzed (covering 260 districts).
      The average age of participants was 73.8 +/- 6.0 years (45.0% men). A multilevel
      binomial logistic regression analysis by sex showed that a denser neighborhood
      network in a district was associated with a lower likelihood of subjective
      dementia symptoms (odds ratio 0.89, 95% confidence interval 0.83-0.96) among
      women. No association was found for men between district-level social capital and
      subjective dementia symptoms. CONCLUSIONS: Fostering structural aspects of social
      capital in a community is a potential dementia-prevention strategy, and
      policymakers should focus on such community-based approaches as well as on
      approaches that target individuals. Geriatr Gerontol Int 2018; 18: 1537-1542.

PMID- 30184612
TI  - Reversed Hand Movement during Sleep in Patients with Obstructive Sleep Apnea.
AB  - OBJECTIVE: Previous findings suggest that hand movement laterality is reversed
      during sleep. The present study aimed to verify this phenomenon and evaluate
      whether the extent of reversal is correlated with the severity of sleep apnea.
      METHODS: A total of 184 participants (mean age: 44.5+/-13.0 years; 81.5% males)
      wore actigraphs on both hands during sleep, and nocturnal polysomnography was
      simultaneously performed. RESULTS: Actigraphic indices of hand movement were
      significantly higher for the left hand than those for the right hand (p<0.001),
      including total activity score, mean activity score, mean score in active periods
      and fragmentation index. Additionally, calculated differences between the
      fragmentation index for the left versus right hands were significantly correlated
      with the apnea-hypopnea index (AHI, r=0.149, p=0.032). The AHI was not
      significantly correlated with differences in hand movement between both hands
      movement assessed by total activity score (r=0.004, p=0.957), mean activity score
      (r=0.011, p=0.876), mean score in active periods (r=-0.080, p=0.255). CONCLUSION:
      More severe symptoms of obstructive sleep apnea was associated with larger degree
      of hand movement reversal at night. This result support the theory that
      homeostatic deactivation occurs in the dominant hemisphere during sleep.

PMID- 30184613
TI  - Biological and Clinical Markers in Panic Disorder.
AB  - Objective: Classifying mental disorders on the basis of objective makers might
      clarify their aetiology, help in making the diagnosis, identify "at risk"
      individuals, determine the severity of mental illness, and predict the course of
      the disorder. This study aims to review biological and clinical markers of panic
      disorder (PD). Methods: A computerized search was carried out in PubMed and
      Science Direct using the key words: "marker/biomarker/clinical
      marker/neurobiology/staging" combined using Boolean AND operator with "panic." In
      addition, the reference lists from existing reviews and from the articles
      retrieved were inspected. Only English language papers published in peer-reviewed
      journals were included. Results: Structural changes in the amygdala, hippocampus,
      cerebral blood level in the left occipital cortex, serotonin 5-TH and
      noradrenergic systems activation, aberrant respiratory regulation, hearth rate
      variability, blood cells and peripheral blood stem cells, hypothalamic-pituitary
      adrenal axis dysregulation were identified as potential candidate biomarkers of
      PD. Staging was identified as clinical marker of PD. According to the staging
      model, PD is described as follows: prodromal phase (stage 1); acute phase (stage
      2); panic attacks (stage 3); chronic phase (stage 4). Conclusion: The clinical
      utility, sensitivity, specificity, and the predictive value of biomarkers for PD
      is still questionable. The staging model of PD might be a valid susceptibility,
      diagnostic, prognostic, and predictive marker of PD. A possible longitudinal
      model of biological and clinical markers of PD is proposed.

PMID- 30184614
TI  - The Association between Social Contacts and Depressive Symptoms among Elderly
      Koreans.
AB  - OBJECTIVE: South Korea has an increasing aging population; thus, the management
      of depressive symptoms in elderly individuals is important. In this population,
      fewer social contacts might be a risk factor for depressive symptoms. We examined
      associations between the frequency of social contacts and depressive symptoms
      among elderly Koreans and factors associated with these symptoms. METHODS: Data
      from 62,845 individuals over 65 years of age enrolled in the 2015 Community
      Health Survey were used in this study. Logistic regression was performed to test
      the association between depressive symptoms and social contacts. RESULTS:
      Individuals who had contact with neighbors less than once a week were more likely
      to experience depressive symptoms [odds ratio (OR): 1.22, 95% confidence interval
      (CI): 1.10-1.35] compared to those who had contact more than once a week.
      Individuals who had frequent contact with neighbors and friends, neighbors and
      relatives, or all three groups were significantly less likely to experience
      depressive symptoms. CONCLUSION: The frequency of social contact with neighbors
      was the most powerful factor associated with elderly adults' depressive symptoms
      among other social relationships. Additional senior welfare centers may
      facilitate the ability of elderly individuals in meeting neighbors, thereby
      reducing the risk of depressive symptoms.

PMID- 30184615
TI  - Prognostic role of beclin-1 in locally advanced non-small cell lung cancer in
      patients receiving docetaxel-platinum induction chemotherapy.
AB  - Background/Aims: The outcome of local treatment for advanced non-small cell lung
      cancer (NSCLC) remains poor, with therapies such as induction chemotherapy (IC)
      yielding conflicting results. This study aimed to assess the clinicopathologic
      and prognostic significance of the excision repair cross-complementation group 1
      (ERCC1), beclin-1, and glucose-regulated protein of molecular mass 78 (GRP78) in
      patients with locally advanced NSCLC receiving docetaxel-platinum IC, along with
      efficacy and safety. Methods: This is a retrospective observational cohort study.
      We reviewed medical records of 31 NSCLC patients receiving docetaxel-platinum IC,
      and conducted immunohistochemical staining of ERCC1, beclin-1, and GRP78.
      Results: Response rate was 67.8% with 10.7 months of median relapse-free survival
      (RFS) and 23.1 months of median overall survival (OS), and no treatment-related
      death was reported. High expression of ERCC1, beclin-1, and GRP78 was identified
      in 67.7%, 87.1%, and 67.7%, respectively. Expression of ERCC1 and GRP78 did not
      reveal statistical significance in survival, whereas high beclin-1 expression
      revealed longer OS (7.6 months vs. 23.2 months; log-rank p = 0.024). In
      multivariate analysis, histologic differentiation (hazard ratio [HR], 3.48; p <
      0.001), stage (HR, 8.5; p = 0.024), and adjuvant treatment (HR, 16.1; p = 0.001)
      were related to RFS, and in OS, stage (HR, 5.4; p = 0.037), adjuvant treatment
      (HR, 8.6; p = 0.004), and beclin-1 expression (HR, 8.2; p = 0.011) were
      identified as significant prognostic factors. Conclusions: Our findings suggest
      that high beclin-1 expression predicts longer survival in locally advanced NSCLC
      and docetaxel-platinum IC is a treatment option that deserves consideration.

PMID- 30184616
TI  - Fixed and Variable Relationship Models to Define the Volume-Value Relationship in
      Spinal Fusion Surgery: A Macroeconomic Analysis Using Evidence-Based Thresholds.
AB  - OBJECTIVE: Increased surgical volume has been associated with improved patient
      outcomes at the surgeon and hospital level. To date, clinically meaningful
      stratified volume benchmarks have yet to be defined for surgeons or hospitals in
      the context of spinal fusion surgery. The objective of this study was to
      establish evidence-based thresholds using outcomes and cost to stratify surgeons
      and hospitals performing spinal fusion surgery by volume. METHODS: Using 155,788
      patients undergoing spinal fusion surgery, we created and applied 4 models using
      stratum-specific likelihood ratio (SSLR) analysis of a receiver operating
      characteristic (ROC) curve. This statistical approach was used to generate 4 sets
      of volume thresholds predictive of increased length of stay (LOS) and increased
      cost for surgeons and hospitals. RESULTS: SSLR analysis of the 2 ROC curves by
      annual surgical volume produced 3 or 4 distinct volume categories. Analysis of
      LOS by annual surgeon spinal fusion volume produced 4 strata: low, medium, high,
      and very high. Analysis of LOS by annual hospital spinal fusion volume produced 3
      strata: low, medium, and high. No relationship between volume and cost could be
      clearly defined based on the generation of ROC curves for surgeons or hospitals
      offering spinal fusion. CONCLUSION: This study used evidence-based thresholds to
      identify a direct, variable relationship model between volume and outcomes of
      spinal fusion surgery, using LOS as a surrogate, for both surgeons and hospitals.
      A fixed relationship model was identified between surgeon and hospital volume and
      cost, as no statistically meaningful relationship could be established.

PMID- 30184617
TI  - VIEKIRA PAK associated drug-induced interstitial lung disease: Case series with
      systematic review of literature.

PMID- 30184618
TI  - High-resolution collision energy control through ion position modulation in atom
      ion hybrid systems.
AB  - We demonstrate an ion shuttling technique for high-resolution control of atom-ion
      collision energy by translating an ion held within a radio-frequency trap through
      a magneto-optical atom trap. The technique is demonstrated both experimentally
      and through numerical simulations, with the experimental results indicating
      control of ion kinetic energies from 0.05 to 1 K with a fractional resolution of
      ~10 and the simulations demonstrating that kinetic energy control up to 120 K
      with a maximum predicted resolution of ~100 is possible, offering order-of
      magnitude improvements over most alternative techniques. Finally, we perform a
      proof-of-principle chemistry experiment using this technique and outline how the
      method may be refined in the future and applied to the study of molecular ion
      chemistry.

PMID- 30184619
TI  - Measurement of the angle dependence of magnetostriction in pulsed magnetic fields
      using a piezoelectric strain gauge.
AB  - We present a high resolution method for measuring magnetostriction in millisecond
      pulsed magnetic fields at cryogenic temperatures with a sensitivity of 1.11*10
      11/Hz . The sample is bonded to a thin piezoelectric plate such that when the
      sample's length changes, it strains the piezoelectric and induces a voltage
      change. This method is more sensitive than a fiber-Bragg grating method. It
      measures two axes simultaneously instead of one. The gauge is small and
      versatile, functioning in DC and millisecond pulsed magnetic fields. We
      demonstrate its use by measuring the magnetostriction of Ca3Co1.03Mn0.97O6 single
      crystals in pulsed magnetic fields. By comparing our data to new and previously
      published results from a fiber-Bragg grating magnetostriction setup, we confirm
      that this method detects magnetostriction effects. We also demonstrate the small
      size and versatility of this technique by measuring angle dependence with respect
      to the applied magnetic field in a rotator probe in 65 T millisecond pulsed
      magnetic fields.

PMID- 30184620
TI  - Coulometric trace humidity measurement in technical gases.
AB  - Trace humidity was measured by using miniaturized planar coulometric sensors in
      technical gases such as hydrogen, nitrogen, helium, nitrous oxide, and synthetic
      air. Frost point temperatures tf in the gases ranged from -60  degrees C to -30 
      degrees C, which is equivalent to a vapour mole fraction xv from 10 MUmol mol-1
      to 376 MUmol mol-1. In addition, the generated humidity was determined by using a
      precision dew point hygrometer as reference. Nonlinear calibration functions were
      calculated that correlated electric current (sensor signal) and reference
      humidity. Parameters of functions were tested with one-way analysis of variances
      (ANOVA) to prove if all used sensors had a similar behavior in the same gas
      during experiments. Results of ANOVA confirmed that averaged functions can be
      applied for trace humidity measurement in nitrogen, helium, nitrous oxide, and
      synthetic air. The calculated functions were negligibly different for nitrogen,
      helium, and synthetic air. In humidified nitrous oxide, a minor change of
      parameters was observed due to lower electrical currents. In total contrast to
      that, the measured sensor signals were significantly higher in humidified
      hydrogen and each sensor required its own calibration function. The reason was a
      recombination effect that favoured multiple measurements of water molecules.
      Nevertheless, it was possible to measure continuously trace humidity in all
      tested gases by using coulometric sensors with an expanded uncertainty below 2 K
      (k = 2).

PMID- 30184621
TI  - 3D-printed capillary for hydrogen filled discharge for plasma based experiments
      in RF-based electron linac accelerator.
AB  - Plasma-based acceleration experiments require capillaries with a radius of a few
      hundred microns to confine plasma up to a centimeter scale capillary length. A
      long and controlled plasma channel allows to sustain high fields which may be
      used for manipulation of the electron beams or to accelerate electrons. The
      production of these capillaries is relatively complicated and expensive since
      they are usually made with hard materials whose manufacturing requires highly
      specialized industries. Fine variations of the capillary shape may significantly
      increase the cost and time needed to produce them. In this article, we
      demonstrate the possibility of using 3D printed polymeric capillaries to drive a
      hydrogen-filled plasma discharge up to 1 Hz of repetition rate in an RF based
      electron linac. The plasma density distribution has been measured after several
      shot intervals, showing the effect of the surface ablation on the plasma density
      distribution. This effect is almost invisible in the earlier stages of the
      discharge. After more than 55000 shots (corresponding to more than 16 h of
      working time), the effects of the ablation on the plasma density distribution are
      not evident and the capillary can still be used. The use of these capillaries
      will significantly reduce the cost and time for prototyping, allowing us to
      easily manipulate their geometry, laying another building block for future cheap
      and compact particle accelerators.

PMID- 30184622
TI  - Characterization of pulsed ultrasound using optical detection in Raman-Nath
      regime.
AB  - In this paper, we describe an optical detection method for the characterization
      of pulsed ultrasound based on acousto-optic interaction. We deduce the
      relationship between the ultrasound and the diffracted light from the principle
      of acousto-optic diffraction in the Raman-Nath regime, which is verified
      experimentally. Five ultrasonic transducers with different central frequencies
      and different focusing types are measured to show the method's performance
      regarding linearity, sound pressure measurement, phase measurement, frequency
      response, and spatial resolution. The experimental results show a good agreement
      with simulation data by CIVA (ultrasonic simulation software, M2M NDT, Inc.) and
      the pulse-echo method.

PMID- 30184623
TI  - Apparatus and method for the growth of epitaxial complex oxides on native
      amorphous SiO2 surface of (001) oriented single crystal silicon.
AB  - The design, fabrication, and performance of an apparatus for the deposition of
      complex oxides with highly uniform thicknesses at controllable deposition rates
      over large area, even on the native amorphous SiO2 layer of (001) oriented single
      crystal Si, are described. The apparatus makes use of the lateral port of a
      spherical chamber. The port is maintained at uniform temperature, and it houses a
      substrate heater. The deposition process is controlled by varying different
      parameters such as target-to-substrate distance, sputtering power, sputtering gas
      atmosphere, substrate temperature, and pulsed plasma growth. The system has been
      tested by growing a series of La0.7Sr0.3MnO3 thin films on Si. The systematic
      strain relaxation and thus the tunable magnetic properties along with the
      presence of high-quality surface morphology of the films indicate that the
      designed system could be used to fabricate different components of oxide
      electronics-based devices over larger area.

PMID- 30184624
TI  - Superconducting radio-frequency virtual cavity for control algorithms debugging.
AB  - Superconducting radio-frequency (SRF) cavities are one of the most important
      elements in modern particle accelerators as they are used for beam acceleration,
      bunch manipulation, bunch focusing and defocusing, etc. Nevertheless, the
      availability of these complex structures prior to their installation in the
      accelerator is limited, either due to a lack of a real cavity or due to the time
      needed for the experiment setup (vacuum, cryogenics, cabling, etc.), and thus it
      can block or delay the development of new algorithms such as low level RF
      control, quench detection, etc. In this paper, we present a hardware virtual
      cavity to be used in hardware-in-the-loop simulations. The system implements a
      cavity electrical model for the transmitted and reflected voltages and more
      advanced features such as mechanical vibration modes driven by Lorentz-force
      detuning or external microphonics, hard quenches, and the Q-slope. As viewed from
      the RF input and output, this virtual cavity acts like a real SRF cavity and can
      replace such a system in early-stage debugging and operation of ancillary control
      systems.

PMID- 30184625
TI  - Real-time signal processing for sub-THz range grating-based distributed fiber
      sensing.
AB  - Distributed optical fiber sensors are an increasingly utilized method of
      gathering distributed strain and temperature data. However, the large amount of
      data they generate presents a challenge that limits their use in real-time, in
      situ applications. This article describes a parallel and pipelined computing
      architecture that accelerates the signal-processing speed of sub-terahertz fiber
      sensor arrays, maintaining high spatial resolution while allowing for expanded
      use of real-time sensing and control applications. The computing architecture
      described was successfully implemented in a field programmable gate array chip.
      The signal processing for the entire array takes only 12 system clock cycles. In
      addition, this design removes the necessity of storing any raw or intermediate
      data.

PMID- 30184626
TI  - Cherenkov radiation-based optical fibre diagnostics of fast electrons generated
      in intense laser-plasma interactions.
AB  - Diagnosing fast electrons is important to understand the physics underpinning
      intense laser-produced plasmas. Here, we demonstrate experimentally that a
      Cherenkov radiation-based optical fibre can serve as a reliable diagnostic to
      characterize the fast electrons escaping from solid targets irradiated by ultra
      intense laser pulses. Using optical fibre loops, the number and angular
      distributions of the escaping electrons are obtained. The data agree well with
      measurements made using image plate stacks. The optical fibre can be operated at
      high-repetition rates and is insensitive to x-rays and ion beams, which makes it
      advantageous over other routinely used fast electron diagnostics in some aspects.

PMID- 30184627
TI  - A new setup for the quantitative analysis of drying by the use of gas-phase FTIR
      spectroscopy.
AB  - Drying rates are important for the manufacture of thin films and in specific for
      the production of electrodes used in electrochemical devices such as fuel cells
      and electrolyzers. The known procedures to investigate time-dependent sample
      compositions and selective evaporation rates are insufficient to obtain mean
      information about the full area instead of a single point analysis. Therefore, a
      new setup is presented using gas-phase Fourier-transform infrared spectroscopy.
      This method analyzes the gas-phase composition to recalculate the layer
      composition in electrode fabrication at any time during drying. According to the
      golden rule of measurement technology, manufacturer specifications are often
      overestimated. Therefore, our alternative procedures were used to evaluate the
      precision of devices used. The calculated measurement precision is confirmed by
      validation. The expected deviation is quantified to be less than 2% for the
      common application. Further on, the relative test-retest standard deviation is
      determined to be 0.3%-0.4%. As a result of the error propagation, the measurement
      precision is limited by the background gas flow rate precision for common
      application. At low volume fractions, the influence of the substance flow rate
      deviations becomes significant. However, further studies will focus on increasing
      the gas flow rate precision.

PMID- 30184628
TI  - Plasma-enhanced reactive linear sputtering source for formation of silicon-based
      thin films.
AB  - In this study, an inductively coupled plasma (ICP)-enhanced reactive sputter
      deposition system with a rectangular target was developed as a linear plasma
      source for roll-to-roll deposition processes. The longitudinal distribution of
      the film thickness indicated the feasibility of uniformity control via the
      control of the power deposition profile of the assisted ICPs. The characteristics
      of Si films were investigated in terms of the film thickness uniformity and film
      crystallinity. The results of Raman and X-ray diffraction measurements indicated
      the crystallization of the Si film with a crystallinity as high as 73%-78% in all
      the samples of the longitudinal position.

PMID- 30184629
TI  - A versatile facility for investigating field-dependent and mechanical properties
      of superconducting wires and tapes under cryogenic-electro-magnetic multifields.
AB  - To investigate the field-dependent and mechanical properties of superconducting
      wires and tapes as a function of cryogenic temperature, transport current, and
      magnetic field, we designed and constructed a versatile facility capable of
      providing cryogenic-electro-magnetic multifields. The facility comprises several
      relatively independent systems to acquire multiple fields and explore various
      properties for superconductors. A superconducting racetrack magnet is
      manufactured to generate a transverse background field up to 3.5 T in a
      relatively large space of a homogeneous region of ?200 mm * H 150 mm. A cryogenic
      system consisting of a vacuum Dewar vessel with a visible window cooled by two
      Gifford-McMahon (GM) cryocoolers for providing refrigeration was built to
      accommodate the background magnet and testing devices, in which one GM cryocooler
      cools the magnet at an operation temperature of about 4 K and the other maintains
      a cryogenic environment for specimens in conduction mode with the cryocooler head
      directly contacting the fixtures. The continuous variations of temperature (4-293
      K) and transport current (0-1000 A) in the superconducting wires and tapes that
      were tested are, respectively, implemented by an integration differentiation
      temperature control with an optional temperature sweep rate and a DC high-power
      supply. Most prominently, the facility can measure the field-dependent and
      mechanical properties for superconducting wires and tapes, which is implemented
      by a mechanical loading and measuring system equipped with a universal testing
      machine possessing a specific design of widening and heightening size and a
      noncontact digital image correlation method with a high-speed, high-resolution
      CCD camera for real-time recording and full-field deformation of specimens. The
      preliminary results of tests verify the multifield functionalities of the
      versatile facility and illustrate the performance of the facility for studying
      the properties of superconducting wires and tapes as a function of magnetic
      field, cryogenic temperature, transport current, and mechanical loading.

PMID- 30184631
TI  - Multispectral medical image fusion scheme based on hybrid contourlet and shearlet
      transform domains.
AB  - Multimodal medical image sensor fusion has revolutionized the medical analysis by
      improving the precision of computer assisted diagnosis. This is incorporated by
      highlighting the complementary information while minimizing the redundant content
      in the fused images from various biomedical sensors like MRI, Computed
      Tomography, and Positron Emission Tomography/Single-Photon Emission Computerized
      Tomography. Multispectral image fusion is a special case of multimodal fusion
      which serves to encompass both spatial and spectral details in the fused image.
      This paper presents a hybrid sub-band decomposition scheme for multispectral
      image fusion comprising of non-subsampled contourlet transform and shearlet
      transform domains. The pre-processing stage involves color transformation of an
      input multispectral image from red-green-blue to YIQ color space. Thereafter,
      both the source images (i.e., panchromatic and multispectral images) after sub
      band decomposition are processed via the application of contrast enhancement,
      weighted-principal component analysis, and max-max algorithms. The low frequency
      coefficients are processed via phase congruency whereas a combination of
      directive contrast and normalized Shannon entropy is applied to high frequency
      coefficients. The objective assessment of image quality has been carried out
      using various reference and no-reference based performance metrics. The
      distinguishing fusion response of the proposed hybrid scheme has been validated
      by the comparisons done with the other fusion approaches.

PMID- 30184632
TI  - Time base evaluation for atom gravimeters.
AB  - Time is an inevitable quantity involved in absolute gravity measurements, and 10
      MHz frequency standards are usually utilized as time base. Here we investigate
      the influence of time base bias on atom-interferometry-based gravity measurements
      and present an onsite calibration of the time base bias relying on an atom
      gravimeter itself. With a microwave source referenced to the time base, the time
      base bias leads to a magnified frequency shift of the microwave source output.
      The shift is then detected by Ramsey spectroscopy with the clock transition of
      87Rb atoms as a frequency discriminator. Taking advantage of available free-fall
      cold atoms and developed techniques of measuring the atom energy level shift in
      atom gravimeters, the calibration achieves an accuracy of 0.6 mHz for the time
      base. And the corresponding error for gravity measurements is constrained to 0.1
      MUGal, meeting the requirement of state-of-the-art gravimeters. The presented
      evaluation is important for the applications of atom gravimeters.

PMID- 30184633
TI  - Measurement of the Hall effect at nanoscale with three probes.
AB  - The Hall effect and its varieties such as quantum, anomalous, and spin Hall
      effects provide indispensable tools for the characterization of electronic and
      magnetic properties of materials, metrology, and spintronics. The conventional
      four-probe Hall configuration is generally not amenable to measurements at
      nanoscale due to current shunting by the Hall electrodes. We demonstrate that
      Hall measurements on the nanoscale can be facilitated by the three-probe Hall
      configuration that avoids the shunting problem. We illustrate the efficiency of
      the proposed approach with anomalous Hall effect-based measurements of individual
      activation events during domain wall motion in magnetic films with perpendicular
      anisotropy.

PMID- 30184634
TI  - Sub-picotesla widely tunable atomic magnetometer operating at room-temperature in
      unshielded environments.
AB  - We report on a single-channel rubidium radio-frequency atomic magnetometer
      operating in unshielded environments and near room temperature with a measured
      sensitivity of 130 fT/ Hz . We demonstrate consistent, narrow-bandwidth operation
      across the kHz-MHz band, corresponding to three orders of magnitude of the
      magnetic field amplitude. A compensation coil system controlled by a feedback
      loop actively and automatically stabilizes the magnetic field around the sensor.
      We measure a reduction in the 50 Hz noise contribution by an order of magnitude.
      The small effective sensor volume, 57 mm3, increases the spatial resolution of
      the measurements. Low temperature operation, without any magnetic shielding,
      coupled with the broad tunability, and low beam power, dramatically extends the
      range of potential field applications for our device.

PMID- 30184635
TI  - Note: Elastic wave velocity measurement using ultrasonic system with two
      reflectors.
AB  - We report an experiment protocol for ultrasonic velocity measurements carried out
      in a synchrotron-based multi-anvil high-pressure apparatus. By adding a second
      reflector in the cell assembly, ultrasonic signals are significantly stabilized
      for experiments where samples experience structural changes such as phase
      transition or partial melting. Features of the elastic wave can be calculated
      from acoustic impedance allowing us to evaluate the possible interference between
      the sample reflection and other internal multiple reflections. This new protocol
      allows various forms of samples including cold-pressed powder samples, for which
      grain size and porosity can be monitored and controlled in situ during the
      annealing process.

PMID- 30184636
TI  - High-performance small- and wide-angle X-ray scattering (SAXS/WAXS) experiments
      on a multi-functional laboratory goniometer platform with easily exchangeable X
      ray modules.
AB  - Small-angle X-ray scattering (SAXS) is a well-established, versatile technique
      for the analysis of nanoscale structures and dimensions, e.g., in liquid
      dispersions, thin solid objects or powder samples. When combined with wide-angle
      X-ray scattering (WAXS), complementary information about the atomic structure can
      be obtained. SAXS experiments traditionally require dedicated instruments to
      achieve the desired angular resolution, sensitivity, stability, and speed of
      measurement. Here we demonstrate how a multi-functional laboratory goniometer
      platform, as widely being used for powder X-ray diffraction and for a variety of
      related techniques, can be configured with pre-aligned X-ray modules that enable
      advanced SAXS/WAXS experiments, without compromising the exceptional versatility
      of the instrument. Line and point collimation setups, as well as quick and easy
      switching between them, are readily possible. Key components are a detachable,
      evacuated beam path and a high-resolution, low-noise hybrid pixel area detector,
      in combination with a hardware interface design that allows to configure the
      instrument with different X-ray modules without the need for re-alignment.
      Software for SAXS data reduction and analysis was developed. The good SAXS/WAXS
      performance and the derived analytical results were verified on various test
      samples, such as gold nanoparticles, colloidal silica, liposomes, dilute protein
      solutions, and solid polymer samples. It is believed that this novel approach to
      SAXS/WAXS instrumentation will help to make this powerful structure analysis
      technique more widely accessible and affordable for multi-user laboratories.

PMID- 30184637
TI  - Stethoscope-type 3omega independent detector for fast measurement of material
      thermal conductivity.
AB  - As one of the most basic properties of materials, thermal conductivity is a key
      parameter to investigate the analysis and design of the particular thermal
      process, such as the analysis of the thermal/cool energy storage and release
      process, the thermal/cool energy storage system design, and so on. Also, it is
      the foundation of energy technology development. In order to overcome the problem
      that the measurement frequency of a polyimide substrate independent detector is
      lower and the measurement time is longer, based on the relationship among 3omega
      detection frequency, thermal wave penetration depth, and thermal properties of
      the substrate material, this paper developed a stethoscope-type 3omega
      independent detector based on a sapphire substrate for fast measurement of
      material thermal conductivity. Nickel, with a high resistance temperature
      coefficient, was used as the metal detector. The influence of the width of the
      nickel metal detector and the thickness of the sapphire substrate on the
      measurement accuracy was analyzed by introducing an effective heat flow ratio.
      The sapphire substrate independent detector was calibrated by using copper,
      aluminum, 304 stainless steel, quartz glass, ethylene glycol, and plexiglass with
      known thermal conductivities. The experiment shows that the measurement frequency
      of the stethoscope detector can be ten times higher than that of a Kapton film
      independent detector. Its measurement time is only one tenth of that of the
      Kapton film independent detector.

PMID- 30184638
TI  - Note: A compact microwave plasma enhanced chemical vapor deposition based on a
      household microwave oven.
AB  - I designed an efficient and compact microwave plasma enhanced chemical vapor
      deposition (MW-PECVD) based on a household 2.45 GHz microwave oven. In the MW
      PECVD, the microwave plasma was sparked by a piece of Cu foil in a low pressure
      down to 1 Pa. The SiC plate is not only used to realize rapid microwave heating
      up but also to prevent the reflected power from damaging the magnetron. To test
      the performance of the system, vertically oriented graphene nanosheets were
      fabricated on the Cu foil. The products were characterized by Raman spectra and
      scanning electron microscope.

PMID- 30184640
TI  - A comparison based digital waveform generator for high resolution duty cycle.
AB  - A comparison-based digital waveform generator has been developed that directly
      enables purely duty cycle controlled digital mass filters. This waveform
      generator operates by the comparison of a periodic waveform and a DC level to
      produce a digital waveform. The improved duty cycle realized by this method of
      waveform generation is demonstrated by producing a mass spectrum of
      electrosprayed lysozyme by varying the duty cycle of a digital waveform applied
      to a quadrupole rod set. Operation and control of the waveform generator using an
      inexpensive open-source microcontroller is discussed.

PMID- 30184639
TI  - A versatile ion beam spectrometer for studies of ion interaction with 2D
      materials.
AB  - We present an ultrahigh vacuum setup for ion spectroscopy of freestanding two
      dimensional solid targets. An ion beam of different ion species (e.g., Xe with
      charge states from 1 to 44 and Ar with charge states from 1 to 18) and kinetic
      energies ranging from a few 10 eV to 400 keV is produced in an electron beam ion
      source. Ions are detected after their transmission through the 2D target with a
      position sensitive microchannel plate detector allowing the determination of the
      ion's exit charge state as well as the scattering angle with a resolution of
      approximately 0.04 degrees . Furthermore, the spectrometer is mounted on a
      swiveling frame covering a scattering angle of +/-8 degrees  with respect to the
      incoming beam direction. By utilizing a beam chopper, we measure the time-of
      flight of the projectiles and determine the energy loss when passing a 2D target
      with an energy uncertainty of about 2%. Additional detectors are mounted close to
      the target to observe emitted secondary particles and are read-out in coincidence
      with the position and time information of the ion detector. A signal in these
      detectors can also be used as a start trigger for time-of-flight measurements,
      which then yield an energy resolution of 1% and an approximately 1000-fold larger
      duty cycle. First results on the interaction of slow Xe30+ ions with a
      freestanding single layer of graphene obtained with the new setup are compared to
      recently published data where charge exchange and energy were measured by means
      of an electrostatic analyzer.

PMID- 30184641
TI  - Design and experimental demonstration of a circularly polarized mode converter
      for high-power microwave applications.
AB  - A novel mode converter that can transform coaxial transverse electromagnetic
      (TEM) mode into circularly polarized TE11 (CPT) mode was developed and
      experimentally studied with high-power microwave (HPM). The mode conversion is
      realized by two steps. First, the TEM mode is converted into linearly polarized
      TE11 (LPT) mode by the webbed-shaped balun structure. Second, the LPT mode is
      transformed into the CPT mode with the insertion of circular-arc diaphragms in a
      circular waveguide. In this paper, the principle of a mode converter working at
      1.57 GHz is demonstrated, as well as the experimental results. The experimental
      and simulation results are in good agreement. At the central frequency, the
      conversion efficiency is more than 99.5%, the measured axial ratio approximates
      to 1.39 dB, and the power handling capacity is in excess of 1.5 GW. These
      measured results meet the demand for narrow-band HPM source application.

PMID- 30184642
TI  - A sensitive, low noise, DC to 12 MHz, large area photodiode preamplifier for
      photothermal heterodyne imaging.
AB  - We report a compact, fast, and low-noise large area photodiode preamplifier
      designed for photothermal heterodyne imaging (PHI). The preamplifier exhibits a
      noise level of 7 nV/Hz1/2 and a bandwidth from DC to 12 MHz sufficient for PHI
      experiments. Simulations of the preamplifier bandwidth and noise agree with the
      observed experimental characterization and performance in our home-built PHI
      system. The observed noise is close to the inherent limitations of the SR844 lock
      in amplifier used. The results indicate that the preamplifier is also useful for
      any other single frequency pump-probe detection technique, such as stimulated
      Raman scattering.

PMID- 30184643
TI  - Force-detected high-frequency electron spin resonance spectroscopy using magnet
      mounted nanomembrane: Robust detection of thermal magnetization modulation.
AB  - In this study, we report a conceptually novel broadband high-frequency electron
      spin resonance (HFESR) spectroscopic technique. In contrast to the ordinary force
      detected electron spin resonance (ESR) technique, which detects the magnetization
      change due to the saturation effect, this method measures the magnetization
      change due to the change of the sample temperature at resonance. To demonstrate
      its principle, we developed a silicon nitride nanomembrane-based force-detected
      ESR spectrometer, which can be stably operated even at high magnetic fields. Test
      measurements were performed for samples with different spin relaxation times. We
      succeeded in obtaining a seamless ESR spectrum in magnetic fields of 15 T and
      frequencies of 636 GHz without significant spectral distortion. A high spin
      sensitivity of 1012 spins/G s was obtained, which was independent of the spin
      relaxation time. These results show that this technique can be used as a
      practical method in research fields where the HFESR technique is applicable.

PMID- 30184644
TI  - Improvement of the shadow tracking setup as a method to measure the velocities
      values of dark dust in order to reduce the risks of radioactive releases or
      explosions.
AB  - The mobilisation of dust is a key security issue in nuclear and industrial plants
      because it can provoke both explosions (in particular temperature and pressure
      conditions) and dangerous radioactive releases. This work is focused on the
      tungsten dust resuspension inside small tank for aerosol removal and DUST
      (STARDUST)-Upgrade, an experimental facility used to reproduce different
      conditions typical of the loss of vacuum accidents. In this paper, the authors
      present the facility and the materials used to mount the experimental setup
      together with the methods and algorithms implemented to track the dust velocity
      vectors. Tungsten dust is also analyzed through scanning electron microscopy and
      X-ray diffraction to find some correlation between the variation of the dust
      morphology, due to the different experimental conditions, with the dust
      mobilisation paths. The materials and methods together with the experimental
      results are analyzed and discussed to demonstrate the implementation with the
      shadow tracking setup presented in the previous facility STARDUST.

PMID- 30184646
TI  - Accurate self-calibrated fiber transfer delay measurement.
AB  - An accurate self-calibrated fiber transfer delay measurement method is
      demonstrated. Using the simplified self-calibration configuration, the
      measurement uncertainty of fiber transfer delay is improved. To demonstrate the
      accuracy of the method, the measurement results of two systems are compared. It
      shows that this method achieves a sub-picosecond accuracy. Besides, the chromatic
      dispersion of fiber under test is also obtained, which is in agreement with the
      nominal value.

PMID- 30184645
TI  - First experimental tests of powerful 250 GHz gyrotron for future fusion research
      and collective Thomson scattering diagnostics.
AB  - A 250 GHz continuous-wave (CW) gyrotron has been developed at the IAP RAS jointly
      with GYCOM Ltd., as a prototype of the microwave source for the envisaged
      prospective nuclear fusion power plants (DEMO). The main applications of such a
      tube are electron cyclotron resonance heating and electron cyclotron resonance
      current drive of magnetically confined plasma as well as its diagnostics based on
      collective Thomson scattering in various reactors for controlled thermonuclear
      fusion (e.g., tokamaks and stellarators). The results of the preliminary
      experimental tests in a pulsed mode of operation are presented. The microwave
      power of up to 330 kW with an efficiency of 30% without collector depression was
      obtained. At an accelerating voltage of 55 kV and an electron beam current of
      12.5 A (which corresponds to the design parameters for CW operation), the
      measured output power was about 200 kW. The TEM00 mode content evaluated at the
      tube output is not less than 98.6%.

PMID- 30184648
TI  - Note: Precision balance for sub-miliNewton resolution direct thrust measurement.
AB  - We attempted to test the suitability of a commercial precision balance as a
      simple alternative sub-miliNewton resolution continuous thrust stand on a
      vertically oriented 300 W-class Hall thruster. The measured thrust data were in
      the range of 1-10 mN with a maximum error of 0.1 mN. The performance of the
      precision balance was compared to the performance of a hanging pendulum thrust
      stand. The measured thrust from the precision balance falls within the standard
      error of the hanging pendulum indicating good quantitative agreement.

PMID- 30184647
TI  - Terahertz wire-grid circular polarizer tuned by lock-in detection method.
AB  - We report the design, construction, and testing of a broadband-tunable terahertz
      circular polarizer, which we developed for our magneto-optical measurements using
      the far-infrared/THz laser source in the range of 0.25-7.5 THz. We present a
      thorough analysis of the lock-in amplifier signal generated by using a rotating
      analyzer with regard to setting the desired state of polarization. The phase
      sensitive detection method is applied to a combination of a wire-grid polarizer
      and a parallel translation mirror providing a tunable retardance. The proposed
      technique is appropriate not only to free-standing grids but also to those
      deposited on transparent substrates which may introduce additional non-linear
      effects. The method is preferred when the distance between the mirror and the
      grid cannot be exactly determined, but the relative displacements are measured.
      The device enables switching between left- and right-handed polarization states
      on a time scale of a few seconds. Practical use of the circular polarizer is
      demonstrated by directly probing the far infra-red magneto-optical properties of
      the two-dimensional electron gas on the 458 MUm laser line.

PMID- 30184649
TI  - Multiple-beam optical interferometry of anisotropic soft materials nanoconfined
      with the surface force apparatus.
AB  - Soft anisotropic materials that change their macroscopic properties in response
      to external stimuli such as light, electric field, or pressure are central to
      several new directions of technology, including optics, micro-mechanics, and
      bioengineering. Responsiveness is fundamentally connected to the anisotropic
      ordering of the material's building blocks at the nanometer scale. Here we
      propose the surface force apparatus as a powerful tool for investigating
      optically anisotropic materials at the nanometer scale using multiple-beam
      optical interference, allowing for simultaneous determination of film thickness,
      alignment, and chiral rotation of the optical axis. We present a method based on
      4 * 4 matrices for calculating the exact transmission and reflection coefficients
      for light incident normal to a planar optical multilayer comprising an arbitrary
      number of chiral anisotropic layers with the helical axis normal to the layer.
      The multilayer can also include uniform birefringent media, optical adsorbing
      (e.g., metals) and isotropic materials. We introduce a technique to analyze and
      interpret the complex multiple-beam interference patterns arising from such
      multilayers and demonstrate it for the case of a twisted nematic liquid crystal
      confined to nanoscale thickness with the surface force apparatus. The analysis
      opens the prospect of studying the effect of strong confinement on the structure
      and response of a wide class of anisotropic materials.

PMID- 30184650
TI  - A modulation based phase difference estimator for real sinusoids to compensate
      for incoherent sampling.
AB  - Phase difference estimation is a fundamental problem in numerous applications.
      However, incoherent sampling (IS) is an inevitable factor which degrades the
      precision of many correlations or Fourier transform-based approaches. In this
      paper, IS and the spectral superposition of real signals are both considered. A
      novel estimator is developed based on modulation and the discrete Fourier
      transform (DFT). With the estimated frequency, the phase difference can be
      obtained by calculating four DFT samples of the modulated signals. Simulations
      and the experimental results have proved their validity as well as their
      superiority over five other methods designed for IS, particularly at high signal
      to-noise ratios. Furthermore, the proposed method can maintain high accuracy even
      when a significant bias occurs with the frequency estimation.

PMID- 30184651
TI  - Invited Review Article: Modeling ion beam extraction from different types of ion
      sources.
AB  - The applications of ion beams are manifold. In most systems, improved extraction
      of the ion beam from the ion source can help to increase the ion beam current or
      to improve the ion beam emittance. Real understanding of the complete system is
      required to achieve improvement of ion beam intensity or ion beam quality.
      Mathematically, the situation is described by a boundary value problem for the
      fields and an initial value problem for ion beam tracking. Whereas the boundary
      value problem is similar for different ion sources, the initial value problem to
      be solved depends on very specific ion source conditions. The influence of
      different parameters like particle density and temperatures on the discharge
      itself is important. For the case of ion beam extraction from an electron
      cyclotron resonance ion source, the problems of a suitable model will be
      discussed in detail. It will be shown that specific diagnostics are required to
      measure specific beam parameters. Such diagnostics are to be included in the
      simulation as well. The overall goal remains to develop a model that can be used
      for further improvements of beam intensity and quality from specific ion sources.

PMID- 30184652
TI  - Non-invasive decoding of hand movements from electroencephalography based on a
      hierarchical linear regression model.
AB  - A non-invasive brain-computer interface (BCI) is an assistive technology with
      basic communication and control capabilities that decodes continuous
      electroencephalography (EEG) signals generated by the human brain and converts
      them into commands to control external devices naturally. However, the decoding
      efficiency is limited at present because it is unclear which decoding parameters
      can be used to effectively improve the overall decoding performance. In this
      paper, five subjects performed experiments involving self-initiated upper-limb
      movements during three experimental phases. The decoding method based on a
      hierarchical linear regression (HLR) model was devised to investigate the
      influence of decoding efficiency according to the characteristic parameters of
      brain functional networks. Then the optimal set of channels and most sensitive
      frequency bands were selected using the p value from a Kruskal-Wallis test in the
      experimental phases. Eventually, the trajectories of free movement and conical
      helix movement could be decoded using HLR. The experimental result showed that
      the Pearson correlation coefficient (R) between the measured and decoded paths is
      0.66 with HLR, which was higher than the value of 0.46 obtained with the multiple
      linear regression model. The HLR from a decoding efficiency perspective holds
      promise for the development of EEG-based BCI to aid in the restoration of hand
      movements in post-stroke rehabilitation.

PMID- 30184653
TI  - Design and laboratory testing of a MEMS accelerometer array for subsidence
      monitoring.
AB  - The in situ monitoring of displacement variation is important for studying the
      seabed subsidence mechanism. To meet the multi-point measurement requirements for
      vertical displacement in subsidence monitoring of the seabed surface, a Micro
      Electro-Mechanical Systems accelerometer array was designed. By sensing the tilt
      angles, displacements on the array can be calculated. The subsidence is
      calculated as the difference in the displacements from the initial values. To
      improve the accuracy of the displacement calculation, a calibration model of the
      tilt angle was presented. The model parameters are computed through a least
      squares estimation method, which is solved by the Levenberg-Marquardt algorithm.
      Experimental results show that the calibration model performs excellently with
      the maximum error of tilt angle being less than 1 degrees  in the measurement
      range (-90 degrees , 90 degrees ). The displacement measurement accuracy of the
      array (2.1 m long) is almost less than 1 cm. Thus, the results show a strong
      agreement between the detected data and actual deformation in the test.

PMID- 30184654
TI  - Monochromatic mammography using scanning multilayer X-ray mirrors.
AB  - A prototype system for breast imaging using monochromatic X-rays has been
      developed using a scanning multilayer X-ray mirror in combination with a
      conventional mammography tube and an imaging detector. The X-ray mirror produces
      a monochromatic fan beam tuned near 19 keV, with an energy bandpass of
      approximately 1.5 keV. Rotating the mirror about the tube's focal spot in
      synchronization with the X-ray generator and detector enables the acquisition of
      monochromatic X-ray images over large areas. The X-ray mirror also can be rotated
      completely out of the beam so that conventional polychromatic images can be
      acquired using a K-edge filter, facilitating direct comparison between the two
      modes of operation. The system was used to image synthetic, tissue-equivalent
      breast phantoms in order to experimentally quantify the improvements in image
      quality and dose that can be realized using monochromatic radiation. Nine custom
      phantoms spanning a range of thicknesses and glandular/adipose ratios, each
      containing both glandular- and calcification-equivalent features, were used to
      measure contrast and signal-difference-to-noise ratio (SDNR). Mean glandular dose
      (MGD) was computed from measured entrance exposure, and a figure-of-merit (FOM)
      was computed as FOM = SDNR2/MGD in each case. Monochromatic MGD ranges from 0.606
      to 0.134 of polychromatic MGD for images having comparable glandular SDNR,
      depending on breast thickness and glandularity; relative monochromatic dose
      decreases with increasing glandularity for all thicknesses. Monochromatic FOM
      values are higher than the corresponding polychromatic FOM values in all but one
      case. Additionally, the monochromatic contrast for glandular features is higher
      than the polychromatic contrast in all but one case as well. These results
      represent important steps toward the realization of clinically practical
      monochromatic X-ray breast imaging systems having lower dose and better image
      quality, including those for digital mammography, digital breast tomosynthesis,
      contrast-enhanced spectral mammography and other modalities, for safer, more
      accurate breast cancer detection, diagnosis and staging.

PMID- 30184655
TI  - Investigation on the optimized algorithm for electrostatic tomography.
AB  - Particle charging in gas-solid two-phase flow is an important concern in many
      industrial processes. The technique of electrostatic tomography (EST) based on
      particle charging can achieve flow regime identification and infer concentration
      and flow rate by detecting the charged particles. Successful application of EST
      depends on the sensitivity map and the image reconstruction algorithm. In this
      paper, the effects of the sensitivity map on EST were demonstrated and a novel
      sensitivity map was presented. Then, optimized Tikhonov iterative algorithm
      (ITIK) was proposed to improve the quality of EST. The simulated results
      illustrate that the novel sensitivity map improves the quality of the
      reconstructed image of EST and the optimized ITIK has better performance in
      reconstructing the image of EST when compared with linearized back-projection
      algorithm, iterative linearized back-projection algorithm, and ITIK. Finally, the
      experimental studies were conducted and the simulated results were validated. The
      results indicate that the novel sensitivity map and the optimized algorithm can
      enable good applications of EST in gas-solid two-phase flow measurement.

PMID- 30184656
TI  - Implementation and application of the peak scaling method for temperature
      measurement in the laser heated diamond anvil cell.
AB  - A new design for a double-sided high-pressure diamond anvil cell laser heating
      set-up is described. The prototype is deployed at beamline 12.2.2 of the Advanced
      Light Source at Lawrence Berkeley National Lab. Our compact design features
      shortened mechanical lever arms, which results in more stable imaging optics, and
      thus more user friendly and more reliable temperature measurements based on
      pyrometry. A modification of the peak scaling method was implemented for
      pyrometry, including an iterative method to determine the absolute peak
      temperature, thus allowing for quasi-real time temperature mapping of the actual
      hotspot within a laser-heated diamond anvil cell without any assumptions on
      shape, size, and symmetry of the hotspot and without any assumptions to the
      relationship between fitted temperature and peak temperature. This is important
      since we show that the relationship between peak temperature and temperature
      obtained by fitting the Planck function against the thermal emission spectrum
      averaged over the entire hotspot is not constant but depends on variable fitting
      parameters (in particular, the size and position of the fitting window). The
      accuracy of the method is confirmed through measuring melting points of metal
      wires at ambient pressure. Having absolute temperature maps in real time allows
      for more differentiated analyses of laser heating experiments. We present such an
      example of the pressure variations within a heated hotspot of AgI at a loaded
      base pressure of 3.8 GPa.

PMID- 30184657
TI  - Novel ultra-wideband test fixture and method for attenuation of the attenuator
      coated dielectric support rod in a helical slow-wave structure.
AB  - In order to measure the attenuation along the dielectric support rod in a helical
      slow-wave structure, a new test fixture and the corresponding test method are
      introduced. The proposed fixture is a transmission line that consists of three
      parts: angle gradient transitions, hyperbolical tapered lines, and parallel
      strips with a sample hole in the middle. The hyperbolical tapered lines on the
      top and bottom sides of the substrate were designed to realize an approximate
      Klopfenstein tapered line. The parallel strips provide a relatively reasonable
      electric field for measuring the attenuation of the dielectric support rod.
      Meanwhile, two modified metal blocks on both sides of each connector are designed
      to suppress unwanted radiation. The test fixture works in the ultra-wideband
      range from 7 GHz to 40 GHz, and it exhibits an insertion loss of less than 3 dB
      and a return loss of more than 10 dB over the whole frequency range. The sample
      hole was regarded as the mutually coupled parallel strip pairs (a four-port
      network), and the odd-even mode method was used to analyze the scattering
      parameters of the single parallel strip. The dielectric support rod deposited by
      the resistive thin-film was measured with the experimental test setup developed
      in this paper. Compared with the method of the double ridge waveguide, the
      measured results present a great agreement with the actual distribution of the
      attenuation in the length ranges from 12 mm to 15 mm, 25 mm to 27 mm, and 46 mm
      to 52 mm, and the differences in other length ranges are explained.

PMID- 30184658
TI  - Note: A novel experimental setup for high-pressure abrasive liquid nitrogen jet.
AB  - A high-pressure abrasive liquid nitrogen (L-N2) jet is considered as an efficient
      rock-breaking technology due to its unique low-temperature characteristic. In
      order to experimentally investigate the impact of an abrasive L-N2 jet on rock
      breakage, a new setup, which considers the low temperature and high expansibility
      of L-N2, is put forward in this note. The setup is composed of four units: the
      power system, nitrogen-gas pressurization system, particle mixing system, and
      impingement system. Both a pre-mixed abrasive L-N2 jet and a post-mixed abrasive
      L-N2 jet can be achieved by this equipment. Moreover, it can also be used to
      investigate the influences of injection parameters and particle parameters on
      rock breakage. A series of experiments have been carried out based on the setup.
      The results further promote the application of an abrasive L-N2 jet.

PMID- 30184659
TI  - Compact high energy x-ray spectrometer based on forward Compton scattering for
      high intensity laser plasma experiments.
AB  - This article describes the design and presents recent results from testing and
      calibration of a forward Compton scattering high energy X-ray spectrometer. The
      calibration was performed using a bremsstrahlung source on the photon scattering
      facility at the gamma Electron linac for beams with high brilliance and low
      emittance accelerator at Helmholtz-Zentrum Dresden-Rossendorf, which provides
      high energy X-ray photons with energies up to 18 MeV. The calibration was
      conducted at different bremsstrahlung end point energies-10.5, 13, 15, and 18
      MeV. Experimental spectra show a systematic increase in the maximum energy,
      photon temperature, and flux. The spectrometer is effective for an energy range
      of 4-20 MeV with 20%-30% energy resolution. The spectrometer operates in low
      vacuum with pressure less than 0.1 mbar. Experimental tests showed that operating
      such a spectrometer in air causes a spuriously enhanced high energy signal due to
      Compton scattering of photons within air. The article also describes the design
      and shielding considerations which helped to achieve a dynamic range greater than
      30 with this spectrometer. The comparison between the experimental results and
      Monte Carlo simulations are also presented.

PMID- 30184660
TI  - Note: Performance of a novel electrostatic quadrupole doublet for nuclear
      microprobe application.
AB  - The newly designed and constructed electrostatic quadrupole doublet (EQD) at the
      University of North Texas (UNT) has achieved mass independent focusing of MeV
      particles to a spot size of 3.3 * 3.5 MUm. The EQD is compared to the Louisiana
      magnetic doublet which is also in use at UNT. Characteristics such as
      demagnification and sensitivity to aberrations are simulated by the matrix
      raytracing software, propagation of rays and aberrations by matrices and compared
      for each focusing system. Particle induced x-ray emission (PIXE) maps of a 2000
      mesh Cu grid are compared and show that both doublets produce suitable spot sizes
      for microprobe analysis. A coarser, 200 mesh grid and incident beams of 2 MeV H+
      and O+ show the EQD to be stigmatic given common aperture sizes and lens
      potentials.

PMID- 30184661
TI  - A practical wide-field Raman imaging method with high spectral and spatial
      resolution.
AB  - Raman imaging has a great advantage in characterizing inhomogeneous systems. A
      practical wide-field Raman imaging platform is developed that shows major
      improvements on imaging speed, sensitivity, and resolution. Different from the
      traditional Raman imaging systems using the wavelength-fixed lasers and the
      chromatic dispersion devices, this system adopts an inverted architecture,
      integrated with a tunable laser and the wavelength-fixed filters. Owing to the
      high transmission of the fixed filters, the imaging sensitivity can be improved 5
      10 times in comparison to the present wide-field Raman imaging setups using
      liquid-crystal tunable filters. Via combining with the high-power tunable laser,
      Raman images could be obtained in minutes and the Raman shift of the images could
      be tuned easily and accurately. The resolution of this system can reach 1.5 cm-1
      in the spectrum and 490 nm in space, which could provide more fingerprint details
      of the analytes. This effective Raman imaging method allowing us to see chemical
      spatial variations on microscale is anticipated to be widely applied in
      scientific research fields.

PMID- 30184662
TI  - Apparatus for combined nanoscale gravimetric, stress, and thermal measurements.
AB  - We present an apparatus that allows for the simultaneous measurement of mass
      change, heat evolution, and stress of thin film samples deposited on quartz
      crystal microbalances (QCMs). We show device operation at 24.85 +/- 0.05  degrees
      C under 9.31 +/- 0.02 bars of H2 as a reactive gas. Using a 335 nm palladium
      film, we demonstrate that our apparatus quantifies curvature changes of 0.001 m
      1. Using the QCM curvature to account for stress induced frequency changes, we
      demonstrate the measurement of mass changes of 13 ng/cm2 in material systems
      exhibiting large stress fluctuations. We use a one-state nonlinear lumped element
      model to describe our system with thermal potentials measured at discrete
      positions by three resistance temperature devices lithographically printed on the
      QCM. By inputting known heat amounts through lithographically defined Cr/Al
      wires, we demonstrate a 150 MUW calorimetric accuracy and 20 MUW minimum
      detectable power. The capabilities of this instrument will allow for a more
      complete characterization of reactions occurring in nanoscale systems, such as
      the effects of hydrogenation in various metal films and nanostructures, as well
      as allow for direct stress compensation in QCM measurements.

PMID- 30184663
TI  - Apparatus for soft x-ray table-top high harmonic generation.
AB  - There has been considerable recent interest in tabletop soft X-ray attosecond
      sources enabled by the new generation of intense, few-cycle laser sources at
      operating wavelengths longer than 800 nm. In our recent work [Johnson et al.,
      Sci. Adv. 4(5), eaar3761 (2018)], we have demonstrated a new regime for the
      generation of X-ray attosecond pulses in the water window (284-540 eV) by high
      harmonic generation, which resulted in soft X-ray fluxes of ~109 photons/s and a
      maximum photon energy of 600 eV, an order of magnitude and 50 eV higher,
      respectively, than previously attained with few-cycle drivers. Here we present
      the key elements of our apparatus for the generation and detection of soft X-ray
      high harmonic radiation in the water window. Of critical importance is a
      differentially pumped gas target capable of supporting the multi-atmospheric
      pressures required to phase-match the high energy emission while strongly
      constraining the gas density, suppressing the effects of ionization and
      absorption outside the interaction region.

PMID- 30184664
TI  - Uncertainty analysis of axial temperature and Seebeck coefficient measurements.
AB  - Experimental investigations of solid materials at elevated temperatures rely on
      the optimized thermal design of the measurement system, as radiation becomes a
      predominant source of heat loss which can lead to large uncertainty in measured
      temperature and related physical properties of a test sample. Advancements in
      surface temperature measurements have reduced thermal losses arising from the
      cold-finger effect using axially inserted thermocouples and from radiation using
      shields or other thermal guards. The leading technology for temperature sensing
      at temperatures up to ~900  degrees C makes use of these design features for
      measuring thermopower, yet uncertainty analysis estimation of this technique is
      not known. This work makes use of finite element modeling to determine spatial
      temperature distributions to obtain the upper limit of confidence expected for
      the axially inserted thermocouple approach when a heated radiation shield is
      incorporated into the design. Using an axially inserted thermocouple to measure
      the sample surface temperature, the temperature variations across the sample hot
      and cold surfaces at 900  degrees C for a temperature drop of 0, 5, and 10 
      degrees C are calculated to be as low as 0.02, 0.21, and 0.41  degrees C,
      respectively, when a heated radiation shield is employed. Uniform temperature
      distribution on the thermocouple cross-wire geometry indicates that the axial
      thermocouple measurement design is indeed effective for suppressing the cold
      finger effect. Using a heated radiation shield is found to significantly reduce
      the temperature gradient across the thermocouples.

PMID- 30184665
TI  - Note: An isobaric sample transfer apparatus for deep-sea pressurized fluid
      sample.
AB  - This paper presents a novel isobaric sample transfer apparatus developed to
      facilitate the continuous culture of microorganisms while also providing the
      capacity for maintaining the sample at in situ pressure during the whole transfer
      and culture process. This apparatus is fitted to the isobaric fluid sampler which
      is used for collecting the isobaric fluid sample. This apparatus can not only
      avoid decompression in traditional sample transfer but also realize the
      integrated function of sample transfer and culture under isobaric conditions. The
      subsampling cylinder can automatically work as a flow culture reactor after
      completing the subsampling of the pressurized sample. Several transfer
      experiments were carried out to demonstrate this design which can make the period
      of transfer automatically.

PMID- 30184666
TI  - A sub-megavolt anti-scattering grid: Fabrication, testing, and Monte Carlo
      simulation.
AB  - X-ray flash radiography is an effective diagnostic in implosive research. While
      scattering reduces the contrast of radiography, the anti-scattering grids can
      effectively intercept the scattered radiation and acquire better images. A
      focused sub-megavolt grid is elaborately manufactured with the combination of
      lithography, etching, and laser drilling. The consistency of Monte Carlo
      simulations and radiographic experiments suggests a transmission of about 36% and
      a 1000 times improvement for the signal to scatter ratio of the grid.

PMID- 30184667
TI  - Note: Investigation of a Marx generator imitating a Tesla transformer.
AB  - A compact Marx generator was built to mimic a spark-gap Tesla transformer. The
      generator produced radio-frequency pulses of up to +/-200 kV and +/-15 A with a
      frequency between 110 and 280 kHz at a repetition rate of 120 Hz. The generator
      tolerated larger circuit-parameter perturbations than is expected for
      conventional Tesla transformers. Possible applications include research on the
      control and laser guiding of spark discharges.

PMID- 30184668
TI  - Novel frequency stability measurement method with whole sample time range.
AB  - A method to measure the frequency stabilities with a nearly whole range of sample
      time is presented. Precision as high as 10-5/100 ns has been obtained by it when
      measuring transient stability with 100 ns sample time, 10-12/s has been obtained
      toward short-term stability with 1 s sample time, and 10-16/day has been obtained
      with regard to long-term stability with 1 day sample time. In addition, because
      the frequency stabilities in a wider range of sample time can correspond to the
      phase noise index more accurately, the phenomena which are difficult to be
      observed in a phase noise curve can be detected through this measurement.

PMID- 30184669
TI  - Diamagnetic current measurements in a solid-state plasma.
AB  - Using a resonant structure, we have established large pressure gradients in a
      magnetized indium antimonide (InSb) plasma. This produces diamagnetic current in
      the milliampere range. The magnetic field generated by the current is sensed with
      a small magnetic coil. The operating frequency is about 230 kHz with a power
      level on the order of 100 mW. The InSb is magnetized with a 1 T magnetic field
      produced with permanent magnets. We show good agreement between our experimental
      measurements and the expected diamagnetic current.

PMID- 30184670
TI  - Note: An ion imaging spectrometer for studying photo-induced fragmentation in
      small molecules.
AB  - A three-dimensional ion imaging spectrometer has been designed and calibrated by
      ion trajectories simulations. We present a recipe for the verification of the
      calibration by obtaining kinetic energy (KE) distribution from the recorded
      flight times alone and consequently correlating the two KE spectra.

PMID- 30184671
TI  - A miniaturized device for the measurement of sheet-metal formability using
      digital image correlation.
AB  - A laboratory-scale device to obtain forming-limit diagram data was designed to
      utilize the Marciniak and Kuczynski (MK) sample geometry. The design uses a high
      resolution photographic camera, automatic trigger, and light-emitting diode (LED)
      lighting to record the time history of deformation calculated with the digital
      image correlation technique. Because the testing device was miniaturized, it was
      possible to halt the forming experiments at intermediate strains and
      recrystallize the MK carrier blank. This permits large formability strains to be
      obtained without cracks developing at the carrier blank's central hole, an
      advantage over full-size specimens and conventional testing rates. A number of
      initial experiments were performed on a zinc alloy sheet (Zn-Cu-Ti) over the
      entire forming-limit range (-0.5 <= epsilon2/epsilon1 <= 1), and the strain
      fields reduced employing the Bragard criterion to obtain limit strains. These
      results are compared favorably to previous data of this material obtained with a
      hemispherical, Nakazima, punch and a circle-grid pattern.

PMID- 30184672
TI  - A floating wide-band current source for electrical impedance tomography.
AB  - The quality of reconstructed images in Electrical Impedance Tomography (EIT)
      depends on two essential factors: first, precision of the EIT hardware in current
      injection and voltage measurement and second, efficiency of its image
      reconstruction algorithm. Therefore the current source plays an important and a
      vital role in EIT instruments. Floating-load current sources constructed using
      sink and source drivers have better performance and higher output impedance than
      grounded-load (single-ended) current sources. In addition, a main feature of this
      kind is that the current source is not connected to the ground potential directly
      but via a large impedance. In this paper, we first focus on recent studies on
      designed EIT current sources, and after that, a practical design of a floating
      load high output impedance current source-operating over a wide frequency band
      will be proposed in detail. Simulation results of the proposed voltage-controlled
      current source (VCCS), along with some other models, will be shown and compared.
      At the end, the results of practical tests on the VCCS and a few EIT images,
      taken using our prototype EIT system coupled with the mentioned VCCS, will be
      illustrated which proves the quality of the proposed current source.

PMID- 30184673
TI  - Dual-mode pushbroom hyperspectral imaging using active system components and feed
      forward compensation.
AB  - Among the methods developed for hyperspectral imaging, pushbroom spatial scanning
      stands out when it comes to achieving high spectral resolution over a wide
      spectral range. However, conventional pushbroom systems are usually realized
      using passive system components, which has limited their flexibility and
      adaptability and narrowed their application scenarios. In this work, we adopt a
      different approach to the design and construction of pushbroom systems based on
      using active internal components. We present a new system concept utilizing an
      internal line scanning unit and a rotating camera mechanism. This enables a dual
      mode imaging system that allows switching between 2D spatial imaging and spectral
      imaging. The line scanning unit, which consists of a narrow slit mounted to a
      linear piezo motor, facilitates the spatial scanning of the target while
      eliminating the laborious relative motion between the target and the imaging
      system, which is needed in conventional spectrographs. A software is developed
      for the automation and synchronization of the active components, which enables a
      novel feed-forward compensation function to compensate the shift in the
      diffraction angle due to the scanning motion of the slit and provide higher
      flexibility in data acquisition.

PMID- 30184674
TI  - Surface action spectroscopy with rare gas messenger atoms.
AB  - Action spectroscopy with inert gas messengers is commonly used for the
      characterization of aggregates in the gas phase. The messengers, often rare gas
      atoms or D2 molecules, are attached to the gas phase aggregates at low
      temperature. Vibrational spectra of the aggregates are measured via detection of
      inert gas desorption following a vibrational excitation by variable-energy
      infrared light. We have constructed an apparatus for the application of action
      spectroscopy to surfaces of solids with the aim of establishing a new method for
      the vibrational spectroscopy of surfaces and deposited clusters. Experiments
      performed for neon covered V2O3(0001) show that this method can provide
      information about surface vibrations. Besides the surface sensitive channel,
      there is also a bulk sensitive one as demonstrated with the example of CeO2(111)
      thin film data. Unlike infrared reflection absorption spectroscopy, normalization
      to a reference spectrum is not required for action spectroscopy data, and unlike
      high resolution electron energy loss spectroscopy, the action spectroscopy method
      does not suffer from moderate resolution nor from multiple excitations. Selective
      decoration of specific surface features with messenger atoms may be utilized to
      focus the spectroscopic information onto these features.

PMID- 30184675
TI  - A time-gated multi-channel x-ray crystal spectrometer on the Shenguang-III laser
      facility.
AB  - An eight-channel x-ray flat crystal spectrometer was developed for high energy
      density physics research at the Shenguang-III (SG-III) laser facility. The
      spectrometer uses trihydroxymethylaminomethane crystals (2d = 8.78 A) to record
      Ti K-shell emission in the photon energy range of 4.65-5.05 keV. The spectrometer
      couples to an x-ray framing camera to achieve time-resolution. This has four
      microstrips, and each strip records two snapshots of the emission image. Based on
      the intersection positioning system with a dual-charge coupled device, the
      alignment system is easily operated and efficient. The instrument was tested and
      used for Au hohlraum plasma diagnosis experiments on SG-III. The He-alpha line
      and its Li-like satellites and the Ly-alpha line of a Ti tracer were detected,
      from which the spectral resolution of the instrument was analyzed. The spectral
      resolution E/DeltaE at the Ti He-alpha line ranges from about 500 to 880 and
      mainly limited by the x-ray source size.

PMID- 30184676
TI  - Wide field of view, real time bioimaging apparatus for noninvasive analysis of
      nanocarrier pharmacokinetics in living model animals.
AB  - Understanding nanocarrier pharmacokinetics is crucial for the emerging
      nanopharmacy, which highly demands noninvasive and real-time visualization of the
      in vivo dynamics of nanocarriers. To this end, we have developed a 2-photon
      excitation and time-resolved (TPE-TR) bioimaging apparatus for the analysis of
      the spatial distribution and temporal evolution of nanocarriers in living model
      animals. The specific polymeric nanocarrier, Eu@pmma-maa doped with Eu-complexes
      luminescing in long persistence at ~615 nm upon near-infrared 2-photon
      excitation, allows the complete rejection of tissue autofluorescence by selective
      luminescence detection. This together with a unique beam shaping scheme for
      homogeneous line excitation, a delicate timing strategy for single-shot line
      scanning, and an equal optical path design for in-plane scan endows the TPE-TR
      apparatus with the following prominent features: an imaging depth of ~10 mm, a
      field of view (FOV) of 32 * 32 mm2 along with a horizontal resolution of ~60 MUm,
      a sub-10 s frame time, and negligible laser heating effect. In addition, a
      combination of the in-plane line scan with the 3D scan of a model animal offers
      the convenience for examining an interested FOV with a millimeter vertical
      resolution. Application of TPE-TR bioimaging to a living mouse reveals rich
      information on the dynamics of nanocarriers including the spatial distribution
      and temporal evolution and the kinetics of domains of interest. The noninvasive
      TPE-TR bioimaging instrumentation with a wide FOV and a large imaging depth will
      find applications in the pharmaceutical development of nanocarriers and relevant
      research fields.

PMID- 30184677
TI  - Driving frequency dependent wave modes of point-focusing electromagnetic acoustic
      transducers.
AB  - This article presents a driving frequency dependent wave mode of point-focusing
      electromagnetic acoustic transducers (PF-EMATs), which is composed of a
      cylindrical permanent magnet and a concentric meander line (CML) coil with a
      varying spacing interval for concentring the ultrasound waves to a point. A
      finite element model is established to simulate the incentive and propagation
      process of ultrasonic waves so that the focusing characteristic, such as
      displacement, amplitude profile, and focal offset, can be obtained, allowing for
      investigation into the driving frequency dependence of wave modes. In addition,
      the universality of driving frequency dependent wave modes is well demonstrated.
      Furthermore, the relationship between the focusing performance of the developed
      PF-EMAT and the coil parameters, inner radius RC and number of turns NC of the
      CML coil, is explored. Finally, the experimental results show good agreement with
      the simulated results and indicate that the presented driving frequency dependent
      wave modes of PF-EMATs employing CML coils could manipulate the wave modes by
      carefully controlling the driving frequency.

PMID- 30184678
TI  - New design techniques of resistive bolometer system for analysis of total
      radiated power.
AB  - Two design techniques for the field of view (FoV) of a resistive bolometer system
      for the analysis of the total radiated power have been developed. The first
      technique is a new concept of the resistive bolometer system having multiple
      apertures to achieve a large viewing angle with one bolometer channel. The second
      technique is an optimization technique of the bolometer location in the major
      radial direction to minimize error of the analysis. Both techniques have been
      examined with a virtual tokamak device. By a FoV designed with both techniques,
      the total radiation power of several radiation profiles can be determined within
      3% error of the analysis with one bolometer channel.

PMID- 30184679
TI  - Fast analysis of collective Thomson scattering spectra on Wendelstein 7-X.
AB  - Two methods for fast analysis of Collective Thomson Scattering (CTS) spectra are
      presented: Function Parametrization (FP) and feedforward Artificial Neural
      Networks (ANNs). At this time, a CTS diagnostic is being commissioned at the
      Wendelstein 7-X (W7-X) stellarator, with ion temperature measurements in the
      plasma core as its primary goal. A mapping was made from a database of simulated
      CTS spectra to the corresponding ion and electron temperatures (Ti and Te ). The
      mean absolute mapping errors are 4.2% and 9.9% relative to the corresponding Ti ,
      for the ANN and FP, respectively, for spectra with Gaussian noise equivalent to
      10% of the average of the spectral maxima in the database at 650 sampling points
      per GHz and within a limited parameter space. Although FP provides some insight
      into the information contents of the CTS spectra, ANNs provide a higher accuracy
      and noise robustness, are easier to implement, and are more adaptable to a larger
      parameter space. These properties make ANN mappings a promising all-round method
      for fast CTS data analysis. Addition of impurity concentrations to the current
      parameter space will enable fast bulk ion temperature measurements in the plasma
      core region of W7-X.

PMID- 30184680
TI  - A novel wavefront measuring camera for quantitative measurement of density in
      high-speed gas flows.
AB  - This paper presents the development of a novel wavefront measuring camera capable
      of detecting both the amplitude and phase of the captured light wave
      simultaneously. The main objective of the present work is to develop a simple
      "aim and shoot" camera system for quantitative estimation of density variations
      in high-speed gas flow fields. The interrogating beam which is a plane wave used
      here gets distorted by flow induced change in refractive index gradients.
      Wavefront distortion is quantitatively measured by inspecting the projected
      pattern through the embedded mask of a modified CMOS image sensor, which samples
      the incoming wavefront space continuously. Post-processing of the captured images
      through Fourier- and windowed Fourier transform schemes reveals the change in
      phase and amplitude of the captured wave. The captured phase of the wavefront is
      used in an iterative tomography scheme to estimate the density distribution of
      the flow field. The utility of the developed camera is demonstrated in the
      quantitative visualization of the high-speed flow fields around test objects
      subjected to hypersonic flows at Mach numbers 8.89 and 5.82 in hypersonic shock
      tunnel facility (HST2) and also to visualize the flow field generated at the exit
      of a convergent-divergent nozzle (Mach number 2.9). It is observed that the
      recovered quantitative density values from the experiments match well with the
      results obtained through computational fluid dynamic simulations demonstrating
      the proficiency of the proposed wavefront measuring camera for high-speed flow
      diagnostics.

PMID- 30184682
TI  - Note: Lever-type bidirectional stick-slip piezoelectric actuator with flexible
      hinge.
AB  - This paper presents a lever-type stick-slip piezoelectric actuator based on the
      lever amplification principle. The proposed actuator can achieve large strokes,
      high velocity, and bidirectional actuation with a single piezoelectric stack. The
      finite element simulation of the lever-type flexible hinge is performed, and the
      designed prototype is tested. When the voltage is 100 Vp-p, the maximum forward
      velocity is 7.69 mm/s under the symmetry of 20%. The maximum reverse velocity is
      7.12 mm/s under the symmetry of 80%. The maximum forward and reverse displacement
      deviation within 10 cycles is 0.88 MUm, and the maximum load can reach 105 g.

PMID- 30184681
TI  - First measurements of remaining shell areal density on the OMEGA laser using the
      Diagnostic for Areal Density (DAD).
AB  - A glass Cherenkov detector, called the Diagnostic for Areal Density (DAD), has
      been built and implemented at the OMEGA laser facility for measuring fusion
      gammas above 430 keV, from which remaining shell ?rhoR? abl can be determined. A
      proof-of-principle experiment is discussed, where signals from a surrogate gas
      Cherenkov detector are compared with reported values from the wedge range filter
      and charged particle spectrometer and found to correlate strongly. The design of
      the more compact port-based DAD diagnostic and results from the commissioning
      shots are then presented. Once absolutely calibrated, the DAD will be capable of
      reporting remaining shell ?rhoR? abl for plastic and glass capsules within
      minutes of a shot and with potentially higher precision than existing techniques.

PMID- 30184683
TI  - A CO2 laser heating system for in situ high pressure-temperature experiments at
      HPCAT.
AB  - We present a CO2 laser heating setup for synchrotron x-ray diffraction inside a
      diamond anvil cell, situated at HPCAT (Sector 16, Advanced Photon Source, Argonne
      National Lab, Illinois, USA), which is modular and portable between the HPCAT
      experiment hutches. The system allows direct laser heating of wide bandgap
      insulating materials to thousands of degrees at static high pressures up to the
      Mbar regime. Alignment of the focused CO2 laser spot is performed using a mid
      infrared microscope, which addressed past difficulties with aligning the
      invisible radiation. The implementation of the mid-infrared microscope alongside
      a mirror pinhole spatial filter system allows precise alignment of the heating
      laser spot and optical pyrometry measurement location to the x-ray probe. A
      comparatively large heating spot (~50 MUm) relative to the x-ray beam (<10 MUm)
      reduces the risk of temperature gradients across the probed area. Each component
      of the heating system and its diagnostics have been designed with portability in
      mind and compatibility with the various experimental hutches at the HPCAT
      beamlines. We present measurements on ZrO2 at 5.5 GPa which demonstrate the
      improved room-temperature diffraction data quality afforded by annealing with the
      CO2 laser. We also present in situ measurements at 5.5 GPa up to 2800 K in which
      we do not observe the postulated fluorite ZrO2 structure, in agreement with
      recent findings.

PMID- 30184684
TI  - Design of PVDF sensor array for determining airflow direction and velocity.
AB  - An airflow sensor comprised of an array of piezoelectric polyvinylidene fluoride
      (PVDF) cantilever sensors mounted on a sensor ring is fabricated. A fluid-solid
      electric coupling model based on the finite element method is presented to obtain
      the mathematical relationship between the normal airflow velocity and the
      response voltage. According to the response voltages from all pieces of PVDF
      cantilevers in the array, the values of the airflow direction and the velocity
      can be calculated. Furthermore, to find a suitable algorithm for error
      calculations and to achieve high accuracy, a method of reducing the flow angle
      error ( Ealphan,cal- ) and flow velocity error ( Deltavn,cal- ) by extracting Um
      of the effective cantilevers can be established. The experimental results show
      that the maximum value of Ealphan,cal- is 1.2 degrees  (at 270 degrees  with 11.1
      m/s) and the minimum value of Ealphan,cal- is 0.3 degrees  (at 135 degrees  with
      11.1 m/s) based on the PVDF sensor array with eight cantilevers. Meanwhile, the
      maximum value of Evn,cal- is 3% (at 315 degrees  with 11.1 m/s), and the minimum
      value of Evn,cal- is 1.5% (at 360 degrees  with 11.1 m/s). In addition, under 20
      random airflow angles at 8 m/s, the error range in airflow velocity is from 1.27%
      to 2.67%, the error range in airflow angle is from 0.34 degrees  to 1.24 degrees
      , and the response time is 20 ms. Therefore, the proposed design for an airflow
      sensory ring array can be used to determine the airflow direction and velocity,
      and the airflow sensor can be miniaturized as a bionic antennae, which is mounted
      on the skin of a piezoelectric autonomous mobile robot for sensing and escaping
      from an attack of the natural enemy.

PMID- 30184685
TI  - An interferometric method for local phase modulation calibration of LC-SLM using
      self-generated phase grating.
AB  - This paper proposes a new interferometric method to measure the phase modulation
      characteristics of a liquid crystal spatial light modulator (LC-SLM). In our
      proposed method, the beam was incident perpendicular to the SLM and the combined
      grayscale pattern loaded into the SLM consisted of three parts. The left part was
      a blazed diffraction grating, and the two right parts were grayscale with
      different constant values. The gray value in the downward section remained
      constant at zero, while it gradually increased from 0 to 255 in the upward
      section. By changing the gray value of the combined grayscale loaded on the LC
      SLM, different sheared fringe patterns, generated by the interference between the
      constant phase-modulated beam and the +1 order diffracted beam of the blazed
      grating, could be obtained. The phase modulation value could then be calculated
      using only one sheared fringe pattern. As a result, our proposed method can
      reduce the effect of environmental vibration or air turbulence and improve
      measurement precision. The experimental results are presented to validate the
      method's potential.

PMID- 30184686
TI  - Mismatch error correction for time interleaved analog-to-digital converter over a
      wide frequency range.
AB  - High-speed high-resolution analog-to-digital conversion is the key part for
      waveform digitization in physics experiments and many other domains. This paper
      presents a new fully digital correction of mismatch errors among the channels in
      Time Interleaved Analog-to-Digital Converter (TIADC) systems. We focus on
      correction with wide-band input signals, which means that we can correct the
      mismatch errors for any frequency point in a broad band with only one set of
      filter coefficients. Studies were also made to show how to apply the correction
      algorithm beyond the base band, i.e., other Nyquist zones in the under-sampling
      situation. The structure of the correction algorithm is presented in this paper,
      as well as simulation results. To evaluate the correction performance, we
      actually conducted a series of tests with two TIADC systems. The results indicate
      that the performance of both TIADC systems can be greatly improved by correction,
      and the effective number of bits is successfully improved to be better than 9.5
      bits and 5.5 bits for an input signal up to the bandwidth (-3 dB) range in the
      1.6-Gsps 14-bit and the 10-Gsps 8-bit TIADC systems, respectively. Tests were
      also conducted for input signal frequencies in the second Nyquist zone, which
      shows that the correction algorithms also work well as expected.

PMID- 30184687
TI  - Integration of pressure-sensitive paint with persistent phosphor: A light-charged
      pressure-sensing system.
AB  - A novel pressure-sensitive paint has been developed by mixing phosphor
      Sr4Al14O25:Eu,Dy with pressure-sensitive luminophore PtTFPP in a polyethylene
      binder. The phosphor particles served as hosts for PtTFPP molecules while
      providing excitation light via their bright blue/green luminescence. The unique
      long afterglow of Sr4Al14O25:Eu,Dy allows the coating to be charged by a light
      source (UV-LED or even sunlight) in advance, and then the luminescent signals can
      be collected by using a color camera for pressure measurement (without an
      external light source). The persistent luminescence and the pressure-sensitive
      signal correspond to the green and red channels, respectively. The errors due to
      time-varying persistent luminescence can be removed by taking an intensity ratio
      between the two channels. The current formulation of this light-charged pressure
      sensitive paint (LC-PSP) has been optimized for the maximum signal level. It
      showed similar pressure sensitivity to typical pressure-sensitive paints (PSPs),
      and its capability was demonstrated through a nitrogen jet impingement
      experiment. This light-charged PSP can be truly free of light source during
      measurement, which greatly simplifies the optical system and avoids errors due to
      the inconsistent illumination field, and thus provides a solution for PSP
      applications in facilities with limited optical access.

PMID- 30184688
TI  - Anisotropic thermal conductivity measurement using a new Asymmetric-Beam Time
      Domain Thermoreflectance (AB-TDTR) method.
AB  - Anisotropic thermal properties are of both fundamental and practical interests,
      but remain challenging to characterize using conventional methods. In this work,
      a new metrology based on asymmetric beam time-domain thermoreflectance (AB-TDTR)
      is developed to measure three-dimensional anisotropic thermal transport by
      extending the conventional TDTR technique. Using an elliptical laser beam with
      controlled elliptical ratio and spot size, the experimental signals can be
      exploited to be dominantly sensitive to measure thermal conductivity along the
      cross-plane or any specific in-plane directions. An analytic solution for a multi
      layer system is derived for the AB-TDTR signal in response to the periodical
      pulse, elliptical laser beam, and heating geometry to extract the anisotropic
      thermal conductivity from experimental measurement. Examples with experimental
      data are given for various materials with in-plane thermal conductivity from 5
      W/m K to 2000 W/m K, including isotropic materials (silicon, boron phosphide, and
      boron nitride), transversely isotropic materials (graphite, quartz, and
      sapphire), and transversely anisotropic materials (black phosphorus).
      Furthermore, a detailed sensitivity analysis is conducted to guide the optimal
      setting of experimental configurations for different materials. The developed AB
      TDTR metrology provides a new approach to accurately measure anisotropic thermal
      phenomena for rational materials design and thermal applications.

PMID- 30184689
TI  - Development and characterization of a helicon plasma source.
AB  - The Helicon Plasma Source (HeliPS) designed and developed at the Centre of Plasma
      Physics-Institute for Plasma Research is a versatile helicon plasma device, which
      operates in a wide range of magnetic field configurations from 50 G to 500 G.
      This device is dedicated to perform a broad range of research activities. The
      main objective for development of the HeliPS is to carry out studies on ion-ion
      plasmas in electronegative gases. In the near future, ion-ion plasmas will be
      formed in electronegative gases in the downstream of the plasma production
      region. Although the system is primarily designed to carry out ion-ion plasma
      experiments, the same system can also be used for experimental studies on some
      basic helicon plasma properties such as wave propagation, wave coupling, and
      plasma instability. At present, argon plasma is produced with a RF power supply
      of 13.56 MHz frequency. External circuit parameters, such as antenna current,
      plasma resistance (Rp), and internal parameters, such as electron density and
      temperature, are measured. The details of the experimental setup development,
      device characteristic, as well as preliminary plasma production and
      characterization to confirm occurrence of the helicon plasma in the system are
      presented in this article.

PMID- 30184690
TI  - A 1-m non-resonant inelastic x-ray scattering spectrometer at BL15U, Shanghai
      Synchrotron Radiation Facility.
AB  - We report the design, construction, and commissioning of a spectrometer for non
      resonant inelastic x-ray scattering study installed at BL15U, Shanghai
      Synchrotron Radiation Facility. It features a 1-m vertical scattering arm. An
      energy resolution of 1.3 eV is achieved based on the 1 m Rowland circle and the
      diced Si(555) crystal analyzer with a fixed Bragg angle of about 88.8 degrees .
      The inelastic squared form factors of 21S + 21P of helium with respect to the
      momentum transfer were measured and compared with the accurate and reliable
      theoretical calculations in order to verify the spectrometer. Furthermore, the
      spectrometer is designed to work in the momentum transfer region of 0 A-1 < q <
      8.68 A-1 and to initially focus on the non-resonant inelastic x-ray scattering
      studies on gaseous samples.

PMID- 30184691
TI  - A high-linearity time-to-digital converter based on dynamically delay-adjustable
      looped carry chains on FPGAs.
AB  - Time-to-digital converters (TDCs) act as the core component in many scientific
      and engineering systems which are based on high-accuracy time measurement.
      Traditionally, field programmable gate array (FPGA) based TDCs are constructed by
      organizing carry chains in the tapped delay line style, though acquiring high
      resolution, the differential nonlinearity (DNL) error is high in the range of 2
      least significant bits (LSBs)-4 LSBs. Additionally, their long used length of the
      carry chain costs rather high resource, which is not friendly for multi-channel
      TDCs. This paper proposes a new TDC architecture based on dynamically delay
      adjustable looped carry chains, which works in the Vernier mode. The TDC contains
      two looped carry chains, and their oscillation period difference (resolution) is
      dynamically adjusted by a personal computer program without manual intervene and
      re-compilation of the TDC circuit. A prototype TDC implemented on a Stratix III
      FPGA obtains the resolution of 26 ps and the DNL less than 1 LSB, but it only
      uses two carry chains of length of 32 each. The proposed TDC architecture opens a
      new way to exploit the capability of the carry chains on FPGAs for high
      performance TDC applications.

PMID- 30184692
TI  - A high-voltage amplifier for traveling-wave Stark deceleration.
AB  - Controlling high voltage is a critical aspect of Stark deceleration, a technique
      that uses electric fields to produce slow molecules. Traditionally, Stark
      deceleration required only commercial high-voltage switches to operate. However,
      a new continuous version of Stark deceleration, which promises significantly
      improved performance, requires chirped sinusoidal voltages. The complexity of the
      electronics needed to run this new decelerator has restricted the implementation
      for all but a few groups. The challenge is to create high-voltage amplifiers that
      have a frequency range of tens of kilohertz down to DC and that can source and
      sink enough current (~1 A) to drive the capacitive load of the decelerator. We
      present a new high-voltage linear amplifier for driving in-vacuum electrodes for
      traveling-wave Stark deceleration. The amplifier has a gain of 12 000, output
      voltages up to +/-10 kV, instantaneous currents up to 1.5 A, and a frequency
      range from 30 kHz down to DC. This makes the amplifier suitable for traveling
      wave Stark deceleration of a supersonic molecular beam down to rest.

PMID- 30184693
TI  - Intensity distortions due to phase-only spatial light modulation:
      Characterization for applications in electronic speckle-pattern interferometry.
AB  - Electronic speckle-pattern interferometry (ESPI) is a powerful tool for precise,
      full-field, and non-contact contouring of optically rough surfaces. Due to the
      interferometric principle, the sensitivity of ESPI is directly related to the
      involved wavelengths and is thereby a global parameter. Surfaces with a broad
      variation of phase gradients, as, for instance, a target with both smooth and
      comparatively steep areas, result in just partially resolvable fringe
      interferograms. In recent studies, spatial light modulators (SLMs) have been
      implemented to adapt the interferometric reference phase front to the measurement
      task and broaden or squeeze the fringe spacing locally in critical areas. This
      method is limited by diffraction effects, observable for all types of phase-only
      SLMs. We demonstrate a straight-forward model, describing the diffraction-based
      intensity distortions occurring in interferograms after wavefront adaptation. The
      aim is to characterize the intensity distortions by means of the proposed model
      and minimize their impact, especially with regard to phase-only spatial light
      modulation in ESPI. For validation, the modeled behavior of SLMs is compared to
      the experimental results, obtained for two different SLM designs. Finally,
      experiments are presented, which demonstrate a successful adaptation of the
      interferometric reference phase front in compliance with the boundary conditions
      determined by the model.

PMID- 30184694
TI  - A supersonic target jet mill based on the entrainment of annular supersonic flow.
AB  - Jet mill is an apparatus that produces superfine powder and is widely used in
      various industries. In this work, a new supersonic target jet mill based on
      aerodynamic theory is presented according to the flow field of a traditional jet
      mill. An annular supersonic flow produced by an annular converging-diverging
      nozzle is used to entrain the central particle flow by the shear mechanism in
      this new supersonic target jet mill. Then, the particle beam concentrating in the
      flow center impacts the target with high kinetic energy after the entrainment of
      the supersonic flow. An apparatus of the annular supersonic target jet mill was
      created to validate the theoretical design. Two types of experiments were
      implemented to estimate its performance. The validation experiments confirmed
      that the gas speed in the collision chamber was approximately 600 m/s and the
      supersonic flow could deliver a kinetic energy of approximately 180 J/s to the
      particles. The particle size reduction of boroncarbide (B4C) and silica (Si) in
      the collision tests showed that the accelerated particles concentrated in the
      supersonic flow center collided on the targets precisely with high collision
      energy.

PMID- 30184695
TI  - Description of complex viewing geometries of fusion tomography diagnostics by ray
      tracing.
AB  - Ray-tracing techniques are applied to bolometry, a diagnostic where the finite
      collection volume is particularly sensitive to the machine and detector
      configuration. A technique is presented that can handle arbitrarily complex
      aperture and collimator geometries, neglecting reflection effects. Sight lines
      from the ASDEX Upgrade bolometer foils were ray-traced with a path tracing
      algorithm, where the optical path is represented by a statistical bundle of ray
      paths connecting the foil surface with the slit geometry. By using the full 3D
      machine model for the detector box and first wall, effects such as occlusion and
      vignetting were included in the calculation of the bolometer's etendue. Inversion
      matrices calculated with the ray-tracing technique were compared with the more
      conventional single-ray approach and shown to be naturally more constrained,
      requiring less regularisation. The two models were tested on a sample radiation
      scenario, and the common single-ray approximation is shown to be insufficient.
      These results are particularly relevant for the divertor where strong emission
      gradients may be present. The technique developed generalises well to arbitrarily
      complex viewing geometries and collimators, opening up a new design space for
      bolometer configurations that might not normally have been considered.

PMID- 30184696
TI  - Ultrafast time-resolved fluorescence at cryogenic temperature.
AB  - Time resolved fluorescence at low temperature can be a powerful tool for the
      study of dynamics and spectroscopy. We have developed a time resolved
      fluorescence apparatus that provides a time resolution of 45 fs at cryogenic
      temperature, which is comparable to the best time resolution at ambient
      temperature. A continuous flow cryostat with a customized vacuum shroud and
      fluorescence upconversion gating by sum frequency generation were employed. A
      reflective Cassegrain type microscope objective lens was used to collect and to
      image the fluorescence to achieve high time resolution. It was demonstrated that
      time-resolved fluorescence spectra can also be measured directly without the
      spectra reconstruction at the same time resolution by in situ adjustment of the
      time delay to compensate the group velocity dispersion. Heat dissipation of the
      sample holder and the actual temperature of the irradiated volume were estimated
      by measuring the steady-state emission spectra of prodan solution in two
      different sample thicknesses, which provides a design consideration for the
      sample cell. The time-resolved fluorescence spectra of prodan, which undergoes
      charge transfer in the excited state, were measured at low temperature to
      demonstrate the capability of the apparatus.

PMID- 30184697
TI  - Printed-circuit-board linear Paul trap for manipulating single nano- and
      microparticles.
AB  - Levitation of very small but macroscopic objects is a rapidly developing
      interrogation technique for nanooptics and optomechanics. Paul traps are one
      mechanism for levitation of charged particles, which enables interrogation of
      novel materials or optically active samples in a virtually interaction-free
      environment, providing a test-bed for completely new experiments. Elementary
      traps have already been demonstrated for nano- and microparticles as a proof-of
      principle for such experiments. We present a linear, segmented Paul trap with a
      printed-circuit-board-based design for levitation of nano- and microparticles, as
      a step toward the more sophisticated tools needed for advanced experiments. We
      describe the trap design, construction, and characterization and address the
      challenging phenomena associated with such a system. This trap provides a step
      toward designing an ideal environment for studies using a variety of isolated
      particles to enable advances in areas including magnetometry, thermodynamics, and
      optomechanics.

PMID- 30184698
TI  - TDLAS-WMS second harmonic detection based on spectral analysis.
AB  - A novel method for the detection of the second-harmonic component of tunable
      laser diode absorption spectroscopy-wavelength-modulated absorption spectroscopy
      is proposed in this study. The proposed method is based on spectral analysis, and
      the second-harmonic component is obtained in the frequency domain through a
      rectangular window. The validity, correctness, and noise immunity of the proposed
      method are verified through simulations and experiments. Experimental results
      demonstrate that the relative detection error level of the proposed method is
      <3%. In contrast to lock-in amplification, the proposed method does not require
      reference signals and low-pass filtering algorithms. These characteristics
      simplify data processing in the proposed method.

PMID- 30184700
TI  - A cryogenically cooled high voltage DC photoemission electron source.
AB  - Linear electron accelerators and their applications such as ultrafast electron
      diffraction require compact high-brightness electron sources with high voltage
      and electric field at the photocathode to maximize the electron density and
      minimize space-charge induced emittance growth. Achieving high brightness from a
      compact source is a challenging task because it involves an often-conflicting
      interplay between various requirements imposed by photoemission, acceleration,
      and beam dynamics. Here we present a new design for a compact high voltage DC
      electron gun with a novel cryogenic photocathode system and report on its
      construction and commissioning process. This photoemission gun can operate at
      ~200 kV at both room temperature and cryogenic temperature with a corresponding
      electric field of 10 MV/m, necessary for achieving high quality electron beams
      without requiring the complexity of guns, e.g., based on RF superconductivity. It
      hosts a compact photocathode plug compatible with that used in several other
      laboratories opening the possibility of generating and characterizing electron
      beam from photocathodes developed at other institutions.

PMID- 30184699
TI  - Inductively coupled 30 T magnetic field platform for magnetized high-energy
      density plasma studies.
AB  - A pulsed high magnetic field device based on the inductively coupled coil concept
      [D. H. Barnak et al., Rev. Sci. Instrum. 89, 033501 (2018)] is described. The
      device can be used for studying magnetized high-energy-density plasma and is
      capable of producing a pulsed magnetic field of 30 T inside a single-turn coil
      with an inner diameter of 6.5 mm and a length of 6.3 mm. The magnetic field is
      created by discharging a high-voltage capacitor through a multi-turn solenoid,
      which is inductively coupled to a small single-turn coil. The solenoid electric
      current pulse of tens of kA and a duration of several MUs is inductively
      transformed to hundreds of kA in the single-turn coil, thus enabling a high
      magnetic field. Unlike directly driven single-turn systems that require a high
      current and low-inductive power supply, the inductively coupled system operates
      using a relatively low-current power supply with very relaxed requirements for
      its inductance. This arrangement significantly simplifies the design of the power
      supply and also makes it possible to place the power supply at a significant
      distance from the coil. In addition, the device is designed to contain possible
      wire debris, which makes it attractive for debris-sensitive applications.

PMID- 30184701
TI  - A novel high thrust-weight ratio linear ultrasonic motor driven by single-phase
      signal.
AB  - This paper presents an ultrasonic motor with a high thrust-weight ratio. The
      miniaturized motor is 13 mm * 5 mm * 3.8 mm in size and uses the first-order
      bending vibration mode (B1 mode) and second-order bending vibration mode (B2
      mode) to realize bidirectional movement through a single-phase driving signal.
      The theoretical trajectory and output thrust of the motor driving foot are
      initially studied. Subsequently, a finite-element model of the motor is
      established, and its dynamic performance is studied. Next, the prototype of the
      motor is fabricated and tested. The results show that errors in the B1 and B2
      modes are 1.976% and 0.436%, respectively. Finally, an experimental setup is
      constructed to test the mechanical properties of the motor. The maximum output
      velocities of the motor is approximately 158 mm/s at 58.917 kHz in the B1 mode
      and approximately 137 mm/s at 113.581 kHz in the B2 mode. The maximum thrust
      force values of the motor in the B1 and B2 modes are approximately 1.32 N and
      1.08 N, respectively, with 7 N preload and 120 Vpp voltage. The overall mass of
      the motor stator is 1.0 g, so the motor thrust-weight ratio reaches 134.69.

PMID- 30184702
TI  - Laser beam angular stabilization system based on a compact interferometer and a
      precise double-wedge deflector.
AB  - To increase the laser beam pointing stability required for precise
      interferometric measurements, we designed an active laser beam angular
      stabilization system. We used two recently proposed techniques: an
      interferometric measurement method of laser beam angular deflection which allows
      compact sensor design and a double wedge-prism beam deflector for precise laser
      beam steering. Our system provides long-term angular stabilization independently
      in the horizontal and the vertical planes, providing a hundredfold reduction of
      the output beam deviations. First, we describe the compact sensor setup with a
      new measurement algorithm prepared specifically for our stabilization system.
      Then, the system is introduced, and experimental evaluation is described. The
      test results show a good performance for the proposed design. We reached a
      reduction in beam angular deviations amplitude down to 100 nrad/h (in terms of
      double standard deviation of beam fluctuations).

PMID- 30184703
TI  - Characteristics of an electron beam extracted from a microwave electron cyclotron
      resonance plasma cathode.
AB  - Under ultra-low pressure, an electron beam is generated by the microwave electron
      cyclotron resonance plasma with a permanent magnet. By means of the Hall coil and
      Miller ampere meter, two electron current signals at the end of the extraction
      anode (Ia) and the sample holder (Is) were measured. The influences of discharge
      power, gas pressure, and accelerating voltage on the electron beam current Is
      were analyzed. The experimental results indicated that the extracted electron
      current can reach 75.1 mA at a gas pressure of 1.4 * 10-3 Pa, an accelerating
      voltage of 8 kV, and an orifice size of 3 mm in diameter. In order to estimate
      the focusing properties of the electron beam by the beam-focusing coil, the
      influence of the coil current on the size of the electron beam spot on the sample
      holder was presented and discussed. The intrinsic mechanism of electron beam
      extraction and propagation is revealed by numerical simulation.

PMID- 30184704
TI  - High-frequency measurements of thermophysical properties of thin films using a
      modified broad-band frequency domain thermoreflectance approach.
AB  - In this work, we present the implementation of a new method to perform high
      frequency thermoreflectance measurements on thin films. The so-called
      differential broad-band frequency domain thermoreflectance method follows broad
      band frequency domain thermoreflectance developed previously [Regner et al., Rev.
      Sci. Instrum. 84(6), 064901 (2013)], without the use of expensive electro-optic
      modulators. Two techniques are introduced to recover the thermal phase of
      interest and to separate it from the unwanted instrumental contributions to the
      recorded phase. Measuring a differential thermal phase by either varying the spot
      size or offsetting the pump and probe beams, the thermophysical properties of
      materials can be extracted. This approach enables the study of nanoscale heat
      transport where non-equilibrium phenomena are dominating.

PMID- 30184705
TI  - Compound fault extraction method via self-adaptively determining the number of
      decomposition layers of the variational mode decomposition.
AB  - Local mean decomposition (LMD) is a self-adaptive method, which has been widely
      applied to extract early fault signals from bearings. However, mode mixing occurs
      during the decomposition process. Moreover, in processing signals with strong
      noise, false frequency components can be generated by variational mode
      decomposition (VMD). To address these problems, a weak fault extraction method
      based on VMD is proposed for rolling bearings. This method regards LMD and the
      combination production function (CPF) as prefilters for VMD. First, LMD is used
      for denoising the original signal, and then the CPF components that contain the
      fault information are combined into a new signal. Second, this method determines
      the decomposition level K of the VMD from the spectral peaks of the recombined
      signal. Finally, this method decomposes the recombined signal using the VMD. The
      main contributions of the proposed method are (i) the CPF method is employed for
      adaptively de-noising, and the power of the fault feature can be improved; (ii)
      the decomposition level K of the VMD can be determined adaptively. After
      processing a simulated signal, fault information of the gears and rolling
      elements is successfully extracted, thereby demonstrating the feasibility of the
      presented method. Moreover, the feasibility of the proposed method is further
      demonstrated in a comparison of results with those obtained from the MOMEDA
      (Multipoint Optimal Minimum Entropy Deconvolution Adjusted) algorithm.

PMID- 30184706
TI  - A compact and alignment-free tube-type device for femtosecond pulses measurement.
AB  - A compact and alignment-free device based on transient grating self-referenced
      spectral interferometry is proposed to realize the temporal profile measurement
      of femtosecond laser pulses. The entire optical setup is composed of two lenses
      and two glass plates on a straight line with tubes, thereby avoiding complicated
      optical alignment and improving the stability and practicality of the device. Two
      51.0 fs and 16.9 fs laser pulses at 800 nm and a 60.6 fs pulse at 1800 nm are all
      successfully measured by this device, which verifies the reliability of the
      device.

PMID- 30184707
TI  - Increasing power and torque capability of brushless direct current motor by
      employing 150-degree conduction mode controlled three-phase voltage source
      inverter.
AB  - With the reduction of magnet costs and the production of high-energy magnets in
      small sizes, permanent magnet brushless motors are used widely in various
      applications from household to medical, industrial, and automation applications.
      Furthermore, permanent magnet brushless motors have some significant advantages
      over the other conventional motors such as induction and brushed motors. Due to
      the popularity of brushless motors, they have become the focus of interest of
      researchers. From the past 30 years to today, the researchers have carried out
      numerous studies in relation to brushless motors. These studies are generally
      sensorless control, adaptive control, different Proportional Integral and
      Derivate (PID) applications, fuzzy control, PI-fuzzy and PID-fuzzy control and
      different Pulse Width Modulation applications and to eliminate torque ripple and
      other control algorithms. Permanent magnet brushless motors can be divided into
      two main groups. One is the permanent magnet synchronous motor and the other one
      is the permanent magnet brushless direct current motor (BLDCM). BLDC motors are
      the most preferred in applications due to their low cost and relatively simple
      drivers. BLDC motors are run with the classical 120-degree conduction mode
      voltage source inverter (VSI). Because BLDC motors run with 120-degree conduction
      mode inverters, power and torque produced by BLDC motors are less than their
      capacity, whereas BLDC motors can provide a better dynamic response, higher
      power, and torque by employing 150-degree conduction mode controlled VSI. In this
      experimental study, it is aimed to design and manufacture a versatile VSI which
      can control the BLDC motor in both 120 and 150-degree conduction modes. Then,
      BLDC motor is run in two conduction modes employing the purposed inverter under
      various loads, and the torque, power, and speed performance of the motor were
      analyzed to demonstrate the effect of the two commutation methods on BLDC motor
      performance. The results of this comparative experimental study have shown that
      the 150-degree conduction mode-controlled inverter provides with the BLDC motor
      generating higher power, torque, and speed than the inverter with 120-degree
      conduction mode.

PMID- 30184708
TI  - Note: Optical fiber two-way time transfer based on single photon counting
      approach.
AB  - We are reporting on time transfer parameters of a newly presented method of the
      Two-Way Time Transfer (TWTT) using the single photon counting approach. The
      method utilizes two Single Photon Avalanche Diode (SPAD) detectors located on
      both ends of the optical channel. Each of the SPAD detectors measures the common
      signal taken from both communication directions on its location. The mixed signal
      is then mathematically decomposed back to the original, separated signals, whose
      time shifts are then measured, and the absolute time shift of the two distant
      time scales is calculated. The photon counting approach was utilized due to its
      great beneficence for the TWTT as most of the systematic errors can be
      eliminated, and, additionally, an optical power of only about -100 dBm is
      necessary for the measurement. It makes the method usable in optical fiber
      channels with the lengths of more than 500 km without any amplification. The
      presented TWTT method can be performed for any communication wavelength when
      proper SPAD detectors are used. In our free-air experiment, we utilized two
      commonly used multimode small form factor pluggable laser modules and the SPAD
      detector developed by our group. The long-term timing stability of the SPAD
      detectors and the timing system used is better than 100 fs. The ultimate
      precision of the time transfer of less than 1 ps for averaging times of hours was
      achieved, and the reliability of the new TWTT method was proven.

PMID- 30184709
TI  - Measurement of the longitudinal energy distribution of electrons in low energy
      beams using electrostatic elements.
AB  - The Transverse Energy Spread Spectrometer (TESS) was designed primarily to study
      the mean transverse energy spread of electrons emitted from photocathode electron
      sources at both room and liquid nitrogen temperatures as a function of quantum
      efficiency through analysis of the photoemission footprint. By reconfiguring the
      potentials applied to different detector elements, TESS can also be used to
      measure the mean longitudinal energy spread of photoemitted electrons. Initial
      plans were to use electrostatic wire meshes as a retarding element which prevents
      the detection of electrons with insufficient energy to overcome a variable
      potential barrier. However, this method has proved impractical and a new method
      has been proposed in which the photocathode bias potential is swept (effectively
      from a state of no electron emission to full emission) and the emitted
      photocurrent is then detected by using a photoemitted charge collector. In this
      article, we present the TESS set-up and analyze this new method to measure the
      longitudinal energy distribution curve. Experimental results are presented and
      compared to simulated results by utilising a custom designed tracking code.

PMID- 30184710
TI  - Tomography diagnostic of plasma radiated power on the spherical tokamak Globus-M.
AB  - A diagnostic system for plasma radiated power tomography on Globus-M was upgraded
      with a new linear array based on silicon photodiodes. The hardware of the
      diagnostic system based on a 256-channel tangential matrix array and a 24-channel
      linear array is described. The algorithm for 2D tomographic reconstruction of
      plasma emissivity is presented. It uses the Tikhonov regularization method and
      anisotropic diffusion functional as a side constraint. Simulated plasma
      emissivity profiles were used to test and assess the capabilities of the
      developed algorithm. Data analysis was carried out in ohmic and neutral beam
      heated discharges to demonstrate the performance of the tomography diagnostic in
      plasmas with different parameters. The presented results illustrate the proper
      functioning of the tomography system that allowed to reveal and study various
      plasma phenomena, including magnetohydrodynamic mode.

PMID- 30184711
TI  - Measurement of anisotropic thermal conductivity of a dense forest of nanowires
      using the 3omega method.
AB  - The 3omega method is a dynamic measurement technique developed for determining
      the thermal conductivity of thin films or semi-infinite bulk materials. A
      simplified model is often applied to deduce the thermal conductivity from the
      slope of the real part of the ac temperature amplitude as a function of the
      logarithm of frequency, which in-turn brings a limitation on the kind of samples
      under observation. In this work, we have measured the thermal conductivity of a
      forest of nanowires embedded in nanoporous alumina membranes using the 3omega
      method. An analytical solution of 2D heat conduction is then used to model the
      multilayer system, considering the anisotropic thermal properties of the
      different layers, substrate thermal conductivity, and their thicknesses. Data
      treatment is performed by fitting the experimental results with the 2D model on
      two different sets of nanowires (silicon and BiSbTe) embedded in the matrix of
      nanoporous alumina templates, having thermal conductivities that differ by at
      least one order of magnitude. These experimental results show that this method
      extends the applicability of the 3omega technique to more complex systems having
      anisotropic thermal properties.

PMID- 30184712
TI  - Design and characterization of an electromagnetic probe for distinguishing
      morphological differences in soft tissues.
AB  - We present a method for designing and optimizing an in-house designed
      electromagnetic probe for distinguishing morphological differences in biological
      tissues. The probe comprises concentric multi-wound coils, the inner being the
      primary coil and the outer being the detector coil. A time-varying voltage is
      imposed on the primary coil, resulting in an induced current in the detector
      coil. For highly conductive samples, eddy currents are induced in the sample and
      inductively couple with the electromagnetic probe. However, in weakly conducting
      samples, the primary coupling mechanism is found to be capacitive though there
      can be a non-negligible inductive component. Both the mutual inductive coupling
      and the capacitive coupling between the sample and the probe are detected as a
      change in the induced voltage of the detector coil using lock-in detection. The
      induced voltage in the detector coil is influenced more by the morphological
      structure of the specimen rather than by changes in electrical conductivity
      within different regions of the sample. The instrument response of the lock-in
      amplifier is also examined with simulated input voltage signals to relate its
      output to specific changes in inductive and capacitive coupling, in order to
      relate sample characteristics to a single voltage output. A circuit element model
      is used to interpret the experimental measurements. It is found that the
      sensitivity of the measurement for a given set of probe characteristics
      (resistances, inductances, and capacitances) can be optimized by adding a small
      amount of capacitance in the external circuit in parallel with the detector coil.
      Illustrative measurements are presented on animal (porcine and bovine) tissue and
      on human liver tissue containing a metastatic tumor to demonstrate the
      capabilities of the probe and measurement method in distinguishing different
      tissue types despite having similar electrical conductivities. Since biological
      tissues are multi-scale, heterogeneous materials comprising regions of differing
      conductivity, permittivity, and morphological structure, the electromagnetic
      method presented here has the potential to examine structural variations in
      tissue undergoing physical changes due to healing or disease.

PMID- 30184713
TI  - Development of a scanning electron microscopy with polarization analysis system
      for magnetic imaging with ns time resolution and phase-sensitive detection.
AB  - Scanning electron microscopy with polarization analysis is a powerful lab-based
      magnetic imaging technique offering simultaneous imaging of multiple
      magnetization components and a very high spatial resolution. However, one
      drawback of the technique is the long required acquisition time resulting from
      the low inherent efficiency of spin detection, which has limited the
      applicability of the technique to certain quasi-static measurement schemes and
      materials with high magnetic contrast. Here we demonstrate the ability to improve
      the signal-to-noise ratio for particular classes of measurements involving
      periodic excitation of the magnetic structure via the implementation of a digital
      phase-sensitive detection scheme facilitated by the integration of a time-to
      digital converter to the system. The modified setup provides dynamic imaging
      capabilities using selected time windows and finally full time-resolved imaging
      with a demonstrated time resolution of better than 2 ns.

PMID- 30184714
TI  - Apparatus for dosing liquid water in ultrahigh vacuum.
AB  - The structure of the solid-liquid interface often defines the function and
      performance of materials in applications. To study this interface at the atomic
      scale, we extended an ultrahigh vacuum (UHV) surface-science chamber with an
      apparatus that allows bringing a surface in contact with ultrapure liquid water
      without exposure to air. In this process, a sample, typically a single crystal
      prepared and characterized in UHV, is transferred into a separate, small chamber.
      This chamber already contains a volume of ultrapure water ice. The ice is at
      cryogenic temperature, which reduces its vapor pressure to the UHV range. Upon
      warming, the ice melts and forms a liquid droplet, which is deposited on the
      sample. In test experiments, a rutile TiO2(110) single crystal exposed to liquid
      water showed unprecedented surface purity, as established by X-ray photoelectron
      spectroscopy and scanning tunneling microscopy. These results enabled us to
      separate the effect of pure water from the effect of low-level impurities present
      in the air. Other possible uses of the setup are discussed.

PMID- 30184715
TI  - A novel phase-shift-based amplitude detector for a high-speed atomic force
      microscope.
AB  - In any atomic force microscope operated in amplitude modulation mode, aka
      "tapping mode" or "oscillating mode," the most crucial operation is the detection
      of the cantilever oscillation amplitude. Indeed, it is the change in the
      cantilever oscillation amplitude that drives the feedback loop, and thus, the
      accuracy and speed of amplitude detection are of utmost importance for improved
      atomic force microscopy operation. This becomes even more crucial for the
      operation of a high-speed atomic force microscope (HS-AFM), where feedback
      operation on a single or a low number of cantilever oscillation cycles between
      500 kHz and 1000 kHz oscillation frequency is desired. So far, the amplitude
      detection was performed by Fourier analysis of each oscillation, resulting in a
      single output amplitude value at the end of each oscillation cycle, i.e., 360
      degrees  phase delay. Here, we present a novel analog amplitude detection circuit
      with theoretic continuous amplitude detection at 90 degrees  phase delay. In
      factual operation, when exposed to an abrupt amplitude change, our novel
      amplitude detector circuit reacted with a phase delay of ~138 degrees  compared
      with the phase delay of ~682 degrees  achieved by the Fourier analysis method.
      Integrated to a HS-AFM, the novel amplitude detector should allow faster image
      acquisition with lower invasiveness due to the faster and more accurate detection
      of cantilever oscillation amplitude change.

PMID- 30184716
TI  - Rotary trigger double spark gap switch for repetitive pulse generator and
      production of silver nanocolloid.
AB  - High-voltage, repetitive pulse generation technology plays a key role in
      underwater discharge applications such as water treatment and metal nanocolloid
      production. For these applications, a high-voltage, high-speed switching
      technology was crucial to swiftly transfer the energy stored in the capacitor to
      the electrodes in water. A rotary-triggered double spark gap switch was developed
      for this purpose in this study. Two spark gaps dedicated for charge and discharge
      were arranged in this switch, and they eliminated the irregular and unstable
      pulse generation due to the simultaneous charging and discharging in the pulse
      generating circuits. Using this technique, pulses with 12 kV and 100 ns rise time
      were generated at a repetition rate of 150 pulses per second and applied to
      underwater discharge to produce silver nanocolloids.

PMID- 30184717
TI  - Time resolved detection of two-plasmon decay using three-halves harmonic emission
      on the National Ignition Facility.
AB  - Supra-thermal (>100 keV) electrons generated by laser plasma interactions can be
      detrimental to the performance of ignition experiments conducted on the National
      Ignition Facility (NIF). On a NIF shot, the amount of electrons is estimated by
      measuring the hard X-rays passing through the hohlraum wall. The primary sources
      of hot electrons in a hohlraum are Stimulated Raman Scattering (SRS) and two
      plasmon decay (TPD). While SRS is well diagnosed on the NIF, there has been no
      diagnosis of TPD. We have designed and implemented a new diagnostic to
      characterize the time history of TPD on the NIF. The instrument provides a time
      resolved measurement of the 3/2 omega harmonic emission which is indicative of
      the presence of TPD. We describe the diagnostic setup, calibration, and the
      preliminary results obtained on NIF hohlraum experiments. We find evidence of a
      correlation between measured hard X-rays generated from the hot electron
      bremsstrahlung and the TPD emission.

PMID- 30184718
TI  - Development of a variable-energy, high-intensity, pulsed-mode ion source for low
      energy nuclear astrophysics studies.
AB  - The primary challenge in directly measuring nuclear reaction rates near stellar
      energies is their small cross sections. The signal-to-background ratio in these
      complex experiments can be significantly improved by employing high-current (mA
      range) beams and novel detection techniques. Therefore, the electron cyclotron
      resonance ion source at the Laboratory for Experimental Nuclear Astrophysics
      underwent a complete upgrade of its acceleration column and microwave system to
      obtain high-intensity, pulsed proton beams. The new column uses a compression
      design with O-ring seals for vacuum integrity. Its voltage gradient between
      electrode sections is produced by the parallel resistance of channels of chilled,
      deionized water. It also incorporates alternating, transverse magnetic fields for
      electron suppression and an axially adjustable beam extraction system. Following
      this upgrade, the operational bremsstrahlung radiation levels and high-voltage
      stability of the source were vastly improved, over 3.5 mA of target beam current
      was achieved, and an order-of-magnitude increase in normalized brightness was
      measured. Beam optics calculations, structural design, and further performance
      results for this source are presented.

PMID- 30184719
TI  - A new method for producing uniform droplets by continuous-ink-jet technology.
AB  - Droplets produced by continuous-ink-jet printing are widely used in various
      fields. The gas pressure in the feedstock tank and the perturbation imposed on a
      capillary jet are the primary parameters to control the formation process of the
      droplets. However, the lack of a simple method for producing perturbation is a
      major limitation of continuous-ink-jet technology. Therefore, based on the
      technology of electromagnetic force perturbation, a novel and simple system to
      produce the desired perturbation frequency is constructed in this article.
      Experiments were conducted with distilled water. The droplet formation process
      experiences three modes with the increase of the disturbance frequency. The
      uniform droplets could be produced in a certain region when the gas pressure in
      the feedstock tank is constant, and the variation of the jet tip had an important
      influence on the uniform droplet formation. The size of droplets could be changed
      by the control of the disturbance frequency.

PMID- 30184720
TI  - V-band Doppler backscattering diagnostic in the TCV tokamak.
AB  - A variable configuration V-band heterodyne Doppler back-scattering diagnostic has
      been recently made operational in the tokamak a configuration variable. This
      article describes the hardware setup options, flexible quasi-optical launcher
      antenna, data-analysis techniques, and first data. The diagnostic uses a fast
      arbitrary waveform generator as the main oscillator and commercial vector network
      analyzer extension modules as the main mm-wave hardware. It allows sweepable
      single or multi-frequency operation. A flexible quasi-optical launcher antenna
      allows 3D poloidal (10 degrees -58 degrees ) and toroidal (-180 degrees  to 180
      degrees ) steering of the beam with 0.2 degrees  accuracy. A pair of fast HE11
      miter-bend polarizers allow flexible coupling to either O or X mode and
      programmable polarization changes during the shot. These have been used to
      measure the magnetic-field pitch angle in the edge of the plasma by monitoring
      the backscattered signal power. Ray-tracing simulations reveal an available k?
      range between 3 and 16 cm-1 with a resolution of 2-4 cm-1. Perpendicular rotation
      velocity estimates compare well against ExB plasma poloidal rotation estimates
      from charge exchange recombination spectroscopy.

PMID- 30184721
TI  - Analyzing the audio signals of degenerative arthritis with an electronic
      stethoscope.
AB  - The advance of modern medical technology has extended people's life and increased
      the average age of the society. Some chronic diseases are due to the aging of the
      population and knee joint aging is a common disease in the elderly. Common joint
      pathology contains degenerative arthritis, arthroncus of knees, and gouty
      arthritis. Knee joints are the largest and the most complicated joints in a human
      body as well as the joint bearing huge pressure. Wrong posture, overuse, or
      vigorous exercise often cause injuries to knee joints, and such injuries could
      easily result in joint pathology and patients falling and breaking bones due to
      pain and powerlessness. An acoustic wave technology, aiming at knee joints, is
      designed to examine a patient's current condition of joints. An electronic
      stethoscope or high-resolution recording equipment is utilized for collecting
      necessary signals, through which the wide-frequency audio signals of knee joints
      could be measured for the analyses and statistics in a back-end computer.
      Besides, it could classify the groups with healthy and degenerative knee joints
      to assist physicians in proceeding non-invasive joint degeneration examination
      clinically and doing the most suitable rehabilitation therapy.

PMID- 30184722
TI  - Corrigendum to: "Mitochondrial targeting of alpha-tocopheryl succinate enhances
      its pro-apoptotic efficacy: A new paradigm for effective cancer therapy" [Free
      Radic Biol Med. 50 (2011) 1546-1555].

PMID- 30184723
TI  - Enhancing the biological activity of vaterite-containing beta-dicalcium silicate
      cement by silane coupling agent for biomaterials.
AB  - Vaterite-containing beta-dicalcium silicate powder (A-V-C2S) was successfully
      grafting modified by 3-aminopropyltriethoxysilane (APTES) through reflux
      agitation. The purpose of this work is to fix the amino groups on the vaterite
      containing beta-dicalcium silicate (V-C2S) powder's surface, which makes the
      powder's surface with positive charge, and further enhanced the combination with
      those negatively charged bioactive molecules or drugs to improve the performance
      of biomaterials. XRD and FT-IR analysis indicated that N-H groups were
      successfully grafted onto the surface of the V-C2S sample on the basis of
      vaterite existence through the process of first grafting then carbonation.
      Moreover, the best grafting modification that refluxing at 70  degrees C for 12 h
      was determined through the quantitative analysis of N-H groups on V-C2S powder's
      surface. The A-V-C2S sample showed a better apatite formation ability after it
      was soaked in stimulated body fluid (SBF), indicating that good apatite
      mineralization. Moreover, the A-V-C2S sample with weak alkali in implanting
      position could stimulate the attachment, proliferation and improve the activity
      of MC3T3-E1 cells. Experimental results demonstrated that, A-V-C2S was expected
      to be a new biomaterial as bone repairing substitute.

PMID- 30184724
TI  - Polyester based nanovehicles for siRNA delivery.
AB  - Small interfering RNA (siRNA) has potential as therapeutic agents against various
      diseases because it can reversibly silence any gene with high efficiency and
      specificity. Unmodified siRNA is a hydrophilic molecule with negative charge,
      which is unstable in the bloodstream and cannot freely cross cell membranes.
      Therefore, the safe and effective delivery systems are necessary to achieve siRNA
      based therapeutics. This review will summarize the polyester nanovehicles which
      are being employed to deliver siRNA, mainly including poly(lactic-co-glycolic
      acid) (PLGA), polylactic acid (PLA), polycaprolactone (PCL) and some other
      polyesters. The characteristics of these polyester nanovehicles including their
      structural properties and functional modifications will be thoroughly
      demonstrated, which is intended to improve the therapeutic effects of siRNA.

PMID- 30184725
TI  - Advances in thermosensitive polymer-grafted platforms for biomedical
      applications.
AB  - Studies on "smart" polymeric material performing environmental stimuli such as
      temperature, pH, magnetic field, enzyme and photo-sensation have recently paid
      much attention to practical applications. Among of them, thermo-responsive
      grafted copolymers, amphiphilic steroids as well as polyester molecules have been
      utilized in the fabrication of several multifunctional platforms. Indeed, they
      performed a strikingly functional improvement comparing to some original
      materials and exhibited a holistic approach for biomedical applications. In case
      of drug delivery systems (DDS), there has been some successful proof of thermal
      responsive grafted platforms on clinical trials such as ThermoDox(r), BIND-014,
      Cynviloq IG-001, Genexol-PM, etc. This review would detail the recent progress
      and highlights of some temperature-responsive polymer-grafted nanomaterials or
      hydrogels in the 'smart' DDS that covered from synthetic polymers to nature
      driven biomaterials and novel generations of some amphiphilic functional
      platforms. These approaches could produce several types of smart biomaterials for
      human health care in future.

PMID- 30184726
TI  - Magneto low-density nanoemulsion (MLDE): A potential vehicle for combined
      hyperthermia and photodynamic therapy to treat cancer selectively.
AB  - In this paper, we introduce a new drug delivery system (DDS) called magneto low
      density nanoemulsion (MLDE), which can carry maghemite nanoparticles and Chlorin
      e6 as an active photosensitizer drug. This design can enhance tumor damage after
      minor heat dissipation and/or minimum visible light photosensitization doses by
      classical magnetic hyperthermia (MHT) and photodynamic therapy (PDT),
      respectively. We establish protocols to prepare the MLDE and to load the drug
      combination onto it. The MLDE prepared herein is nanometric (<200 nm), has high
      encapsulation efficiency, and is stable for at least 12 months in water
      dispersions. Flow cytometry results demonstrated that MLDE presents targeted
      selectivity toward the MCF-7 breast cancer cell line but not in NHI-3T3 mouse
      fibroblast cell lines, because the MCF-7 cancer cell surface contains
      overexpressed low density lipoprotein (LDL) receptors. Despite this targeted
      effect, MHT or PDT alone does not prompt significant antiproliferative outcomes.
      On the other hand, MHT and PDT in combination induce a strong and synergic action
      on MCF-7 cells and reduce the cell viability. In conclusion, the developed MLDE
      deserves further investigation because it is biocompatible, displays good
      encapsulation efficiency, and is highly stable. Moreover, it is selectively taken
      up by cancer cell surfaces with receptor recognition based on LDL receptor
      overexpression, which potentiates the action of combined MHT and PDT.

PMID- 30184727
TI  - Design of lactoferrin modified lipid nano-carriers for efficient brain-targeted
      delivery of nimodipine.
AB  - Blood-brain barrier (BBB) was the major obstacle for efficient delivery of
      therapeutic agents to brain tissue. To overcome this barrier, a novel lactoferrin
      modified long circulation nanostructured lipid carriers (Lf-NLC) was designed and
      synthesized for the efficient delivery of neuroprotective agent nimodipine (NMD)
      to brain tissue. NMD loaded Lf-NLC was optimized to exhibit a small and uniform
      particle size distribution and high loading content. More interestingly, Lf-NLC
      showed the excellent neuroprotective effect due to the efficient intracellular
      delivery NMD, in PC12 based stroke cell model induced by sodium nitroprusside
      (SNP). Cellular uptake assay indicated that Lf-NLC could be internalized into
      cytoplasm via Lf-receptor mediated endocytosis pathway. In vivo biodistribution
      assay demonstrated Lf-NLC could efficiently deliver therapeutic agent to brain
      tissue, indicating its promising application in brain delivery.

PMID- 30184728
TI  - Recent advances of PLGA micro/nanoparticles for the delivery of biomacromolecular
      therapeutics.
AB  - Recent advancements in biopharmaceutical industry have facilitated the
      development of novel bioactive macromolecular therapeutics. One of the challenges
      towards the clinical use of these biomacromolecules lies in the selection of
      appropriate carriers to protect, deliver and release them in vivo to maximize
      their pharmacological effects. Micro/nanoparticles made from biodegradable poly
      (d,l-lactic-co-glycolic acid) (PLGA) have been explored as delivery vehicles for
      therapeutics. Due to their excellent biocompatibility and controllable
      biodegradability, PLGA micro/nanoparticles could protect macromolecules from
      instant degradation in vivo while allowing tunable release rate and profile. In
      this review, recent progress in the design, fabrication/formulation and
      application of PLGA based micro/nanoparticles for the controlled delivery of
      biomacromolecules are discussed. Special focuses will be on the novel loading
      methods and releasing mechanisms of macromolecules as well as the in vivo
      applications of therapeutic macromolecule-loaded PLGA micro/nanoparticles.

PMID- 30184729
TI  - Biodegradable polyester shape memory polymers: Recent advances in design,
      material properties and applications.
AB  - Shape memory polymers (SMPs) is a class of well-studied smart materials with a
      variety of applications. In recent years, biodegradable polyester SMPs have
      received increasing attention from the research community both as academic
      interest and for their potential usefulness in biomedicine and soft robotics. In
      this contribution, the most recent progress in the area of biodegradable
      polyester-based SMPs is summarized with regards to their structural designs,
      thermomechanical properties, shape memory performance and some emerging
      characteristics, followed by a discussion on the specific applications of these
      SMPs in biomedicine and soft robotics. The prospective research direction for the
      future development of polyester SMPs as advanced functional materials is also
      discussed.

PMID- 30184730
TI  - Designing function-oriented artificial nanomaterials and membranes via
      electrospinning and electrospraying techniques.
AB  - The sister technologies, electrospinning and electrospraying provide a facile and
      universal synthesis method for the continuous preparation of nanostructured
      materials. Through adjusting the synthesis parameters, rich electrospun and
      electrosprayed nanomaterials, scaffolds, membranes with tunable composition
      (inorganic, polymeric, hybrid, etc.), shape (sphere, films, scaffold, etc.),
      morphology and inner structure (solid, hollow, core-shell, co-axial, etc.) can be
      selectively elaborated. This review provides an overview of the design of
      functional nanostructured materials, porous scaffolds and membranes by
      electrospinning and electrospraying techniques. Key experimental parameters and
      synthesis strategy are emphasized to reveal the synthesis-component-structure
      property relationship and eventually realize the targeted functions through
      predictable synthesis. Potential applications in tissue engineering, medicine,
      membrane filtration and lithium battery are highlighted.

PMID- 30184731
TI  - Recent advances in the development of biodegradable PHB-based toughening
      materials: Approaches, advantages and applications.
AB  - Polyhydroxybutyrate (PHB) is a natural biodegradable polymer that is produced by
      many types of bacteria as an intracellular energy storage material. Due to its
      numerous advantages such as biodegradability, biocompatibility, availability and
      with physical properties comparable to petroleum-based thermoplastics, PHB is a
      potential substitute in biomedical and packaging fields. However, several
      physical drawbacks, such as high production cost, thermal instability, and poor
      mechanical properties, due to secondary crystallization and slow nucleation rate,
      limit its competition with traditional plastics in industrial and biomedical
      applications. Thereby, many attempts have been employed to improve the material
      performance of toughened PHB so as to achieve greater competitiveness and
      sustainability. In this review, the most recent developments of PHB-based
      toughening materials are discussed with respect to their approaches and
      strategies, which includes: drawing and thermal treatment, blending with
      materials from natural sources and synthetic polymers, as well as forming
      reinforced composites with natural fibers and inorganic fillers. The alternation
      of PHB chemical structure to form various types of functional copolymers with
      enhanced materials performance is also summarized. The expanded utilization of
      these newly developed sophisticated PHB materials as engineering materials and
      the biomedical significance in different domains are also addressed.

PMID- 30184733
TI  - Fabrication of luminescent TiO2:Eu3+ and ZrO2:Tb3+ encapsulated PLGA
      microparticles for bioimaging application with enhanced biocompatibility.
AB  - Rare earth is of great interest because of their unique optical properties,
      especially the rich luminescent spectra. In this study, we developed a facile one
      pot microwave-assisted synthesis of luminescent Eu3+ doped TiO2 nanoparticles and
      Tb3+ doped ZrO2 nanoparticles. As a result, the emitting centers (Eu3+ and Tb3+)
      were all well dispersed in the amorphous host oxide materials, leading to high
      luminescence. The obtained TiO2:Eu3+ and ZrO2:Tb3+ nanoparticles were then
      encapsulated into PLGA microparticles for bio-applications. These luminescent
      microparticles were then proven to be highly stable, biocompatible and of low
      cytotoxicity. We successfully demonstrated the bioimaging of live cells using the
      red-luminescent TiO2:Eu3+ nanoparticles and green-luminescent ZrO2:Tb3+
      nanoparticles embedded PLGA microparticles. The microwave-assisted synthetic
      methodology can be further developed to be general method to prepare oxide
      nanoparticles.

PMID- 30184732
TI  - Accelerated corrosion of 316L stainless steel in simulated body fluids in the
      presence of H2O2 and albumin.
AB  - 316L stainless steel has been widely used for orthopedic devices. Inflammatory
      response and direct contact with abundant proteins after implantation lead to
      corrosion issues of biomedical stainless steels. The effect of combination of
      H2O2 and albumin on the corrosion of 316L stainless steel has been investigated
      for the first time in simulated body fluids at 37  degrees C with electrochemical
      and long term immersion tests. ICP-MS measurement after 16 weeks immersion
      reveals that the total concentration in the presence of both species was
      substantially higher than physiological saline alone, and even higher than the
      sum of H2O2 alone and albumin alone. Electrochemical polarisation curves and
      electrochemical impendence spectra show that albumin accelerated anodic
      dissolution and suppressed cathodic reaction, while H2O2 promoted cathodic
      reaction. Also, H2O2 and/or albumin promoted meta-stable/stable pitting corrosion
      and decreased charge transfer resistance. Accelerated corrosion of 316L stainless
      steel in the presence of both species was attributed to the promoted formation of
      Fe oxides and CrOOH by H2O2 and the largely favoured dissolution of these oxides
      by the addition of albumin, significantly accelerating Fe and Cr release. The
      synergistic interaction between both species indicates significant
      underestimation of corrosion rate evaluated solely in physiological saline. These
      findings suggest the necessity of using more realistic solutions to evaluate
      corrosion resistance of biomedical alloys for future in-vitro studies.

PMID- 30184734
TI  - Impact of minor alloying with C and Si on the precipitation behavior and
      mechanical properties of N-doped Co-Cr alloy dental castings.
AB  - The addition of carbon and silicon as minor alloying elements was examined as a
      means to improve the mechanical properties of novel nitrogen-doped Co-Cr-based
      alloy dental castings. Samples of Co-32Cr-9W-Si-0.25N-C (mass%) alloys were
      prepared using a dental-casting machine. Microstructural analysis was performed
      on the alloys using scanning electron microscopy, electron-backscatter
      diffraction, electron-probe microanalysis, and X-ray diffraction, with a
      particular focus on the precipitation behavior. The findings were compared with
      thermodynamic predictions and examined in relation to the tensile properties and
      Vickers hardness at room temperature. All of the prepared alloys had a face
      centered-cubic gamma-phase matrix, with grains measuring a few millimeters in
      diameter and consisting of dendritic substructures. The precipitation of the
      intermetallic sigma-phase, which occurred in the interdendritic regions with
      solidification segregation of Cr and W, was replaced with M23C6 through the
      addition of carbon. This significantly increased the ultimate tensile strength of
      the alloys without severe loss of ductility, although the 0.2% proof stress did
      not change. The addition of silicon, on the contrary, promoted the formation of
      the precipitates, which included M6C and the sigma-phase, making the alloys
      brittle. The results of this study highlight the role of minor alloying elements,
      such as carbon and silicon, on the microstructural and mechanical properties; the
      findings also shed light on the significance of precipitation control in dental
      castings of Co-Cr alloys, which should aid the design of novel dental alloys.

PMID- 30184735
TI  - Antibacterial activities and biocompatibilities of Ti-Ag alloys prepared by spark
      plasma sintering and acid etching.
AB  - In this work, Ti-Ag sintered alloys (Ti-Ag) with different Ag contents were
      prepared by a spark plasma sintering (SPS) technique, which is a new, efficient
      and convenient method of powder metallurgy. The Ti-Ag samples were then treated
      with a mixture of 40 wt% hydrofluoric acid (HF) and nitric acid (HNO3). The
      surface features, ion release, antibacterial activities and biocompatibilities of
      the acid-etched Ti-Ag (Ti-Ag(AE)) samples were systematically characterized. The
      surface characterization results revealed the formation of micropits and
      particles with high Ag contents. Antibacterial experiments demonstrated that the
      antibacterial ratios of the Ti-Ag samples increased significantly after the acid
      etching treatment, and the particles with high Ag contents are thought to play a
      key role in the antibacterial mechanism. Biocompatibility experiments indicated
      that the cell proliferation, cell morphology, and osteoblastic differentiation
      did not significantly differ between the pure titanium (cp-Ti) and Ti-Ag(AE)
      samples. The Ti-Ag(AE) samples with 3 wt% and 5 wt% Ag not only possessed
      sustained antibacterial activities for at least 30 days but also did not have
      impaired biocompatibility.

PMID- 30184736
TI  - The effect of ethylene oxide sterilization on electrospun vascular grafts made
      from biodegradable polyesters.
AB  - The study describes the detailed examination of the effect of ethylene oxide
      sterilization on electrospun scaffolds constructed from biodegradable polyesters.
      Different fibrous layers fabricated from polycaprolactone (PCL) and a copolymer
      consisting of polylactide and polycaprolactone (PLCL) were investigated for the
      determination of their mechanical properties, degradation rates and interaction
      with fibroblasts. It was discovered that the sterilization procedure influenced
      the mechanical properties of the electrospun PLCL copolymer scaffold to the
      greatest extent. No effect of ethylene oxide sterilization on degradation
      behavior was observed. However, a delayed fibroblast proliferation rate was
      noticed with concern to the ethylene oxide sterilized samples compared to the
      ethanol sterilization of the materials.

PMID- 30184737
TI  - Fiber-reinforced colloidal gels as injectable and moldable biomaterials for
      regenerative medicine.
AB  - Hydrogels are the preferred material choice for various strategies in
      regenerative medicine. Nevertheless, due to their high water content and soft
      nature, these materials are often mechanically weak, which limits their
      applicability. This study demonstrates mechanical reinforcement of colloidal gels
      at microscale using discrete polyester fibers, as confirmed by rheological,
      compression and nanoindentation tests. This reinforcement strategy results in
      injectable and moldable colloidal gels with improved mechanical performance. The
      fully organic gels presented here are cytocompatible and can maintain their
      mechanical integrity under physiological conditions. Consequently, these gels
      exhibit a strong potential for applications in tissue engineering and
      regenerative medicine.

PMID- 30184739
TI  - In vivo anti-obesity efficacy of curcumin loaded nanofibers transdermal patches
      in high-fat diet induced obese rats.
AB  - Obesity as a dominant problem in developed countries which is known to be basic
      step of so many diseases is subjected to find a solution for in this work.
      Curcumin containing polyvinyl alcohol-gelatin nanofibers which ranging from 200
      to 250 nm in diameter as a transdermal drug delivery system for declining volume
      of subcutaneous adipose tissue is investigated here. Morphology and synthesis
      method of nanofibers is designed and optimized by statistical software and a
      totally uniform and reproducible method of synthesis is used for preparation of a
      transdermal patch. Effectiveness of delivery system in transport of drug through
      skin is confirmed by side by side arrangement transdermal diffusion cells. This
      transdermal patch used for animal test showed 4 to 7% decrease in total amount of
      adipose tissue estimated by whole body magnetic resonance imaging technique.

PMID- 30184738
TI  - A novel biocompatible chitosan-Selenium nanoparticles (SeNPs) film with
      electrical conductivity for cardiac tissue engineering application.
AB  - Cardiomyopathy is the leading cause of mortality in the world and economic
      burdens on national economies. A cardiac patch approach aims at regenerating an
      infracted heart by providing healthy functional cells to the injured region via a
      film carrier substrate, and providing mechanical and electrical support. Selenium
      acts as an important element in the prevention and treatment of cardiovascular
      diseases but their health-related effects have not been fully explored.
      Limitation is the fact that cardiac electrophysiology was only globally
      personalized, thus missing the potential localized pathological features in vivo.
      The epidemiological aspects of plasma levels of selenium and other lipid
      parameters in cardiomyopathy patients (30 nos) from South Tamilnadu, India were
      studied. The epidemiological data showed significant differences between plasma
      selenium, Glutathione per oxidase (Gpx) and High reactive-C Protein in
      cardiomyopathy patients when compared to the control. As a novel approach, in the
      present study chitosan-Selenium nanoparticles (SeNPs) film was used to produce
      electrical conductivity in the cardiac patches. The prepared chitosan-SeNPs film
      was characterized by Scanning Electron microscopy with Energy Dispersive X ray
      spectrum (SEM-EDX). The electrical and mechanical properties of the chitosan
      SeNPs film were also studied. The chitosan-SeNPs film had compression of elastic
      modulus (67.1% elongation) and tensile strength of 419 kPa. The electrical
      conductivity of chitosan-SeNPs film was measured as 0.0055S cm-1. The H9C2 cells
      were very well grown in chitosan-SeNPs film and proliferated. In our study, we
      confirm the potential of SeNPs-chitosan film for use as substrates to grown
      cellular behavior via electrical stimulation, mechanical strength and as
      biocompatible film for cardiac tissue engineering applications.

PMID- 30184740
TI  - Prolonged release of bone morphogenetic protein-2 in vivo by gene transfection
      with DNA-functionalized calcium phosphate nanoparticle-loaded collagen scaffolds.
AB  - In the combination of scaffolds immersed in growth factor solutions, the release
      of growth factors mainly depends on scaffold degradation. However, the release of
      bone morphogenetic protein (BMP)-2 at an appropriate concentration during the
      stage of tissue regeneration would enhance bone regeneration. To achieve this
      condition, the present study was performed to investigate the effects of
      scaffolds combined with gene transfection using non-viral vectors.
      Nanohydroxyapatite-collagen (nHAC) scaffolds cross-linked with 1-ethyl-3-(3
      dimethylaminopropyl) carbodiimide hydrochloride (EDC) or ascorbic acid/copper
      chloride, and a collagen scaffold (Terdermis(r)) were prepared, loaded with BMP-2
      encoding plasmid DNA-functionalized calcium phosphate nanoparticles (CaP), naked
      plasmid DNA, or BMP-2 solution, and implanted in rats. The yield of released BMP
      2 and its releasing period, respectively, were larger and longer from the
      scaffolds loaded with CaP than from those incubated with BMP-2 solution. In
      addition, the alkaline phosphatase activity induced by the CaP-loaded scaffolds
      was higher. Histological analysis showed that released BMP-2 could be observed on
      the macrophages or multinuclear giant cells surrounding the nHAC fragments or
      collagen fibres. TRAP-positive or OCN-positive sites were observed in all groups
      and a mineralization area was observed in the Terdermis(r)/CaP sample. The
      present study demonstrates that gene transfection by scaffold loaded with CaP
      gene transfer vectors induces a larger yield of BMP-2 for a longer period than by
      scaffolds loaded with BMP-2 solution or naked plasmid.

PMID- 30184741
TI  - Novel magneto-responsive nanoplatforms based on MnFe2O4 nanoparticles layer-by
      layer functionalized with chitosan and sodium alginate for magnetic controlled
      release of curcumin.
AB  - Remotely assisted drug delivery by means of magnetic biopolymeric nanoplatforms
      has been utilized as an important tool to improve the delivery/release of
      hydrophobic drugs and to address their low cargo capacity. In this work, MnFe2O4
      magnetic nanoparticles (MNPs) were synthesized by thermal decomposition, coated
      with citrate and then functionalized with the layer-by-layer (LbL) assembly of
      polyelectrolyte multilayers, with chitosan as polycation and sodium alginate as
      polyanion. Simultaneous conductimetric and potentiometric titrations were
      employed to optimize the LbL deposition and to enhance the loading capacity of
      nanoplatforms for curcumin, a hydrophobic drug used in cancer treatment. ~200 nm
      sized biopolymer platforms with ~12 nm homogeneously embedded MNPs were obtained
      and characterized by means of XRD, HRTEM, DLS, TGA, FTIR, XPS and fluorescence
      spectroscopy techniques to access structural, morphological and surface
      properties, to probe biopolymer functionalization and to quantify drug-loading.
      Charge reversals (+/-30 mV) after each deposition confirmed polyelectrolyte
      adsorption and a stable LbL assembly. Magnetic interparticle interaction was
      reduced in the biopolymeric structure, hinting at an optimized performance in
      magnetic hyperthermia for magneto-assisted drug release applications. Curcumin
      was encapsulated, resulting in an enhanced payload (~100 MUg/mg).
      Nanocytotoxicity assays showed that the biopolymer capping enhanced the
      biocompatibility of nanoplatforms, maintaining entrapped curcumin. Our results
      indicate the potential of synthesized nanoplatforms as an alternative way of
      remotely delivering/releasing curcumin for medical purposes, upon application of
      an alternating magnetic field, demonstrating improved efficiency and reduced
      toxicity.

PMID- 30184742
TI  - Characterisation of a new plasma-enhanced film to improve shear bond strength
      between zirconia and veneering ceramic.
AB  - The aim of this study was to develop and characterise a new plasma-enhanced
      chemical vapor deposition (PECVD) film for improving shear bond strength (SBS)
      between yttria-stabilised tetragonal zirconia (Y-TZP) and veneering ceramic. In
      total, 192 Y-TZP samples (13 * 5.4 * 5 mm) were divided into 6 groups: control -
      no treatment (C), airborne-particle abrasion with 27 MUm aluminum oxide particles
      (Al27), 110 MUm aluminum oxide particles (Al110), and 250 MUm aluminum oxide
      particles (Al250), application of liner for zirconia (L) and the PECVD film
      application (P). The Y-TZP surface was characterised by means of Scanning
      Electronic Microscopy (SEM), Energy-dispersive Spectroscopy (EDS), atomic force
      microscopy (AFM), surface profilometry and surface-free energy (SFE). SBS between
      Y-TZP and veneering ceramic was tested before and after thermocycling (20,000
      cycles of 5 and 55  degrees C), and failure mode was also evaluated. Data were
      analysed by ANOVA and Tukey's HSD test (alpha = 0.05). Data analysis showed that
      PECVD film had no effect on surface roughness of Y-TZP (p > 0.05 vs control),
      whilst the other groups presented higher roughness values (p < 0.05). All
      treatments increased SFE, except the Al27 group. The highest SBS was presented by
      the P group (p < 0.05), and values were similar to those of the Al27 group (p =
      0.107). Mixed failures were prevalent in all groups, and premature failures were
      found only in Al groups after thermocycling. Whilst PECVD treatment did not
      affect Y-TZP surface roughness, high SBS between Y-TZP and the veneering layer
      was observed. Therefore, PECVD treatment is a promising alternative to improve
      the performance of bi-layer zirconia-based restorations.

PMID- 30184743
TI  - From formulation of acrylamide-based hydrogels to their optimization for drug
      release using response surface methodology.
AB  - This study conducted on the structure of modified acrylamide-based hydrogel by
      synthesizing the nano composites. The hydrogels employed in this study were
      provided through a combination of acrylamide monomers, sodium carboxymethyl
      cellulose (NaCMC) and magnesium oxide (MgO) nanoparticles by crosslinking
      polymerization. N,N,N',N'-tetramethylethylenediamine and ammonium persulfate as
      the initiator was applied in the structure of the polymer. Findings of the study
      considered the nano composites consisting of MgO have the highest swelling ratio
      compared to pure Aam hydrogels. Thus, MgO is an appropriate nanoparticle to be
      used in the nano composites. Response surface methodology (RSM) based on a
      central composite design (CCD Design) was applied to optimize the preparation
      variables of a hydrogel consisted of MgO, NaCMC. With the swelling ratio for
      acrylamide-based hydrogel as the response, the effects of two variables, i.e. MgO
      and NaCMC were investigated. The effects of pH, temperature, MgO, and NaCMC on
      the drug release were investigated using the CCD design. The predicted
      appropriate drug release conditions for the hydrogel at the highest rate of
      temperature (37.50  degrees C) and pH: 4.10, is at its highest value, while the
      lower drug release is at temperature 38  degrees C and pH 3.50. With the desired
      value of MgO (0.01 g) and amount of NaCMC (0.1 g).

PMID- 30184744
TI  - Surface modification of titanium with hydroxyapatite layer induced by phase
      transited lysozyme coating.
AB  - Surface modification of titanium with a hydroxyapatite (HAP) coating can improve
      the bioactivity of pristine titanium. The traditional techniques for coating HAP
      on titanium involve nonmild treatments using strong bases or acids or high
      temperatures. In this study, the coating of HAP was carried out by a novel
      methodology called phase-transited lysozyme-assisted hydroxyapatite formation
      (PAH); in this process of biomimetic mineralization, the abundant functional
      carboxyl groups of phase-transited lysozyme (PTL) were responsible for the
      nucleation of HAP crystals by concentrating Ca2+ ions at the interface between
      PTL and CaCl2 solution and for the subsequent growth of HAP crystals occurring in
      simulated body fluid (SBF). In vitro and in vivo experiments verified that the
      surface of titanium modified with the HAP/PTL-Ti multilayer was endowed with
      improved biocompatibility and osteoinductivity compared with those of pristine
      titanium. Therefore, PAH is a simple, rapid, low-cost and green process for the
      surface modification of titanium with an HAP coating and thus will be a promising
      methodology for the surface modification of titanium implants.

PMID- 30184745
TI  - Serine adsorption through different functionalities on the B12N12 and Pt-B12N12
      nanocages.
AB  - The present work reports the adsorption of serine in the neutral and zwitterionic
      forms on the pure and Pt-decorated B12N12 fullerenes by means of density
      functional theory (DFT) and time-dependent density functional theory (TD-DFT)
      calculations. The binding energy of serine over the fullerene has been studied
      through its hydroxyl (-OH), carboxyl (-COOH), and amine (-NH2) functional groups.
      Based on our analysis, the binding energy of serine in zwitterionic form (F: 
      1.52 eV) on B12N12 fullerene is less stable than that of the neutral form (C: 
      1.61 eV) using the M06-2X functional. Our results indicated that the most stable
      chemisorption state for serine is through its amine group (I: -2.49 eV)
      interacting with the Pt-decorated B12N12 fullerene in comparison with the
      carbonyl group (J: -1.92 eV). The conductivity of the B12N12 and Pt-decorated
      B12N12 fullerenes is influenced by the energy band gap variation when serine is
      adsorbed upon the outer surface of fullerenes. Understanding the adsorption of
      serine on B12N12 and Pt-decorated B12N12 fullerenes provide fundamental knowledge
      for future applications in biomolecules and metal surfaces.

PMID- 30184746
TI  - Vasorelaxant effect of standardized extract of Cecropia glaziovii Snethl
      encapsulated in PLGA microparticles: In vitro activity, formulation development
      and release studies.
AB  - In this study, the standardized dry extract of C. glaziovii (SDE) provided a
      significant vasorelaxant effect after contractions induced by phenylephrine in
      rat aortic rings in an endothelium-dependent manner, confirming that endothelial
      factors are needed to stimulate this response. A vasorelaxation close to that of
      acetylcholine was achieved, justifying the development of new formulations for
      this plant material. In this context, microparticles were selected to encapsulate
      SDE and the double emulsion technique was considered because of the hydrophilic
      nature of plant material. Two experimental designs were applied. Firstly, the
      effect of formulation parameters on particle size, size distribution and
      encapsulation efficiency (EE) was evaluated. As low EE was achieved, the effect
      of the osmotic pressure of the external phase was evaluated in a second
      experimental design. The presence of the osmotic agent (NaCl) impacted positively
      on the EE and slower in vitro release profile was obtained, which is desired in
      controlled release systems. The formation of denser and less porous particle
      surface, which was identified by SEM analysis, contributes to explain these
      findings. Microstructures showed to be a promising delivery system for the C.
      glaziovii SDE considering that a sustained release was achieved.

PMID- 30184748
TI  - Formulation characterization and in vitro drug release of hydrogel-thickened
      nanoemulsions for topical delivery of 8-methoxypsoralen.
AB  - Psoralens are lipophilic molecules used to treat skin diseases such as vitiligo
      and psoriasis, among them, 8-Methoxypsoralen (8-MOP) is the most used to topical
      skin application. Topical treatment with psoralens can be limited due to
      insufficient drug penetration into the skin layers. Nanoemulsions have attracted
      much attention due to their as dermal delivery systems for lipophilic drugs such
      as 8-MOP. However, nanoemulsions feature low viscosity, which might be unsuitable
      for topical application. In this work, we produced hydrogel-thickened
      nanoemulsions using chitosan with different molecular weight as thickening
      polymer to overcome the low viscosity attributed to nanoemulsions. The aim of
      this study is to characterize oil-in-water (o/w) nanoemulsions and hydrogel
      thickened nanoemulsions based on two different essential oils to in vitro
      controlled release of 8-MOP. In a previous work, we have reported production,
      stability and in vitro transdermal release of such formulations. Here, 8-MOP
      loaded nanoemulsions and hydrogel-thickened nanoemulsions were characterized
      regarding their morphology, rheological behavior, and in vitro drug release
      kinetics. Hydrogel-based systems presented a gel-like rheological behavior, being
      classified as weak gels. 8-MOP in vitro release from hydrogels-based formulations
      using clove essential oil showed strong dependency chitosan molecular weight. On
      the other hand, hydrogel-thickened nanoemulsions using sweet fennel oil as inner
      phase, showed an unexpected pH-dependent behavior not fully understood at the
      moment. These results need further investigation, nevertheless hydrogel-thickened
      nanoemulsions revealed to be interesting and complex dermal delivery systems for
      poorly soluble drugs.

PMID- 30184747
TI  - Ultra-fast, highly efficient and green synthesis of bioactive forsterite
      nanopowder via microwave irradiation.
AB  - Forsterite (Mg2SiO4) has recently attracted considerable attention in different
      fields because of its wide range of applications. In this paper, pure forsterite
      nanopowders were synthesized by an ultra-fast, highly efficient and green method
      for the first time. Microwave irradiation was used to synthesize forsterite
      nanopowder. The formation of highly crystalline forsterite nanopowder was
      confirmed by X-ray diffraction (XRD) and energy dispersive X-ray spectrometer
      (EDS) analyses. Scanning electron microscopy (SEM) and transmission electron
      microscopy (TEM) analyses showed that the agglomerated powder composed of
      nanocrystalline particles with the mean particle size of ~100 nm. Microwave
      irradiation significantly accelerated the rate of the reactions and dramatically
      decreased reaction times from hours to minutes and seconds. In vitro bioactivity
      evaluation was performed by soaking the forsterite samples in simulated body
      fluid (SBF). Results indicated that synthesized forsterite nanopowder via
      microwave irradiation method possessed excellent apatite-forming ability in SBF.
      Cell viability results showed that synthesized forsterite nanopowder not only
      showed no cytotoxicity but also improved cell proliferation. Alkaline phosphatase
      (ALP) activity assay indicated that the fabricated forsterite nanopowder could
      facilitate the MG63 osteoblast-like cells to proliferate and differentiate.
      Therefore, microwave-assisted synthesis technique could be considered as a novel,
      safe and high efficient method in saving time and energy for bioactive forsterite
      nanopowder production.

PMID- 30184749
TI  - Compressive characteristics of radially graded porosity scaffolds architectured
      with minimal surfaces.
AB  - Scaffolds with gradient pore characteristics have received a great deal of
      attention as they can better mimic the structure of the native tissues and
      concurrently meet both biological and mechanical requirements. In the present
      study, the effects of porosity geometry and porosity gradient patterns on the
      deformation mechanism and compressive mechanical properties of the structures
      were investigated in the context of stretching (I-WP and P surfaces) versus
      bending dominated (D surface) triply periodic minimal surface (TPMS) based
      architectures. Different gradient patterns were found to significantly alter the
      deformation mechanism. Radial gradient patterns (perpendicular to loading
      direction) provide higher deformability while longitudinally graded scaffolds
      suffer from low failure strain. In the stretching dominated architectures
      vertical cracks propagated under compression due to the materials transverse
      expansion under compression. Deformations in the bending dominated architectures,
      however, were accompanied by a progressive collapse owing to the shearing of the
      struts. In general, stretching dominated structures showed the higher mechanical
      properties and provided more efficiency under mechanical loads. Finite Element
      simulations also demonstrated a high capability for predicting the deformation as
      well as mechanical responses (especially for elastic properties) and can be used
      as a tool for designing multifunctional gradient porous scaffolds.

PMID- 30184751
TI  - In vitro corrosion behavior and biocompatibility of nanostructured Ti6Al4V.
AB  - Ti6Al4V (TC4) alloy has long been used as a bone interfacing implant material in
      dentistry and orthopedics due to its excellent biocompatibility and mechanical
      properties. The performance of TC4 can be further tailored by altering its grain
      structures. In this study, by means of sliding friction treatment (SFT), a nano
      grained (NG) surface layer with an average grain size of <=100 nm on the topmost
      surface was successfully generated on coarse-grained (CG) TC4 alloy sheet. It was
      shown that the NG surface possessed notably enhanced corrosion resistance in
      physiological solution compared to the CG surface, due to the formation of
      thicker and denser passive film facilitated by surface nanocrystallization.
      Additionally, the NG surface with stronger hydrophilicity favorably altered the
      absorption of anchoring proteins such as fibronectin (Fn) and vitronectin (Vn)
      that can mediate subsequent osteoblast functions. The in vitro results indicated
      that the NG surface exhibited remarkable enhancement in osteoblast adherence,
      spreading and proliferation, and obviously accelerated the osteoblast
      differentiation as compared to CG surface. Moreover, the NG surface also
      demonstrated good hemocompatibility. These findings suggest that SFT can endure
      bio-metals with advanced multifunctional properties for biomedical applications.

PMID- 30184750
TI  - Fabrication and characterization of chicken feather keratin/polysaccharides
      blended polymer coated nonwoven dressing materials for wound healing
      applications.
AB  - In this research work, three kinds of nonwoven wound dressings were developed
      from chicken feather keratin (CFK-NW), keratin-sodium alginate (CFK-SA-NW) and
      keratin-chitosan (CFK-CS-NW) and characterized using FTIR and SEM. The physical
      characteristics such as air permeability, thickness and areal density test
      results revealed the suitability of fabricated materials for wound dressing
      applications. CFK-SA-NW and CFK-CS-NW indicated a positive antibacterial effect
      against Gram's positive Staphylococcus aureus and Gram's negative Klebsiella
      pneumoniae and Escherichia coli bacteria with the zone of inhibition enhanced
      over >2.0 cm. Moreover, the biomedical potentials of dressing materials has been
      investigated by cell viability and cytotoxicity tests. Further, the wound healing
      ability was demonstrated using in vivo model (Albino Wistar rat). The fabricated
      materials exhibited good support for cell viability and a strong
      cytocompatibility. Furthermore, the hundred percent wound healing ability of CFK
      CS-NW, CFK-SA-NW, CFK-NW and untreated control rats was observed at 15, 17, 21
      and 23 days, respectively, Moreover, the wound healing potential of CFK-CS-NW and
      CFK-SA-NW was found to be better than that of CFK-NW and control group of rats.
      The outcome of the present study discloses the prospective applications of the
      developed materials as wound dressing biomaterial.

PMID- 30184752
TI  - Feeder-free culture for mouse induced pluripotent stem cells by using UV/ozone
      surface-modified substrates.
AB  - Pluripotent stem cells (PSCs), especially induced PSCs (iPSCs), have great
      potential for regenerative medicine. Conventionally, PSCs are cultured and
      expanded efficiently on feeder cell layers or on cell-adhesive matrices. Large
      scale iPSC expansion in an undifferentiated state without laborious culturing
      procedures and high manufacturing costs for the adhesive matrix is urgently
      required to integrate iPSCs into therapeutic applications. For this, feeder
      layers or cell-adhesive matrix coating have to be removed from the iPSC culture
      system. To enable feeder- and matrix coating-free culture conditions, we focused
      on a UV/ozone surface treatment technique for polystyrene cell culture substrates
      to improve PSC adhesion and proliferation. In this study, changes in the
      molecular structure of UV/ozone-modified polystyrene were characterized to
      optimize the surface chemistry for iPSC. Mouse iPSCs (miPSCs) were cultured on
      the UV/ozone-modified polystyrene substrates without feeder layers. As a result,
      large polymeric chains of polystyrene were dissociated into small polymeric
      chains and oxidized to form ester and carboxylic acid functional groups by the
      UV/ozone treatment. Moreover, it was suggested that optimal valance of these
      modified molecules enabled the feeder- and matrix coating-free culture of miPSC
      with maintaining pluripotency.

PMID- 30184753
TI  - Fabrication of magnetite-functionalized-graphene oxide and hexadecyltrimethyl
      ammonium bromide nanocomposite for efficient nanosorption of sunset yellow.
AB  - A novel magnetic nanocomposite based on magnetite nanoparticles-functionalized
      graphene oxide and hexadecyltrimethyl ammonium bromide has been synthesized (MAGO
      CTAB) by a facile route for efficient, fast and sensitive binding with Sunset
      Yellow (SY). The MAGO-CTAB (27 +/- 3 nm) has been successfully characterized by
      transmission electron microscopy, X-ray diffraction, Fourier transform infrared
      spectroscopy and vibrating sample magnetization techniques. The influences of
      different experimental parameters on the % SY removal efficiency were fully
      investigated. The adsorption rates of SY by MAGO-CTAB were conducted by fitting
      the experimental data to four kinetic models. Langmuir, Freundlich, Temkin and
      Dubinin-Radushkevich (D-R) adsorption isotherms were applied to study SY removal.
      The adsorption-desorption stability performance of the novel magnetic nanosorbent
      was evaluated and confirmed after 5 cycles. The designed MAGO-CTAB was
      successfully utilized for removal of SY from different food and soft drink
      samples with excellent recoveries values (98-103%).

PMID- 30184754
TI  - Collagen-silica bio-composite enriched with Cynodon dactylon extract for tissue
      repair and regeneration.
AB  - Development of biomaterials for tissue engineering applications is of great
      interest to meet the demand of different clinical requirements. The wound heal
      dressing biomaterials should necessarily contain well-defined therapeutic
      components and desirable physical, chemical and biological properties to support
      optimal delivery of therapeutics at the site of the wound. In this study, we
      developed collagen-silica wound heal scaffold incorporated with the extract of
      Cynodon dactylon, characterized and evaluated for its wound heal potential in
      vitro and in vivo against collagen (Col) and Collagen-silica (CS) scaffolds that
      served as controls. The prepared Collagen-Silica-Cynodon extract (CSCE) scaffold
      exhibits porous morphology with preferable biophysical, chemical, mechanical and
      mass transfer properties besides its controlled biodegradation at the wound site.
      Stability of CSCE was found to be better than that of native collagen due to
      intermolecular interactions between collagen and constituents of C. dactylon as
      confirmed by FTIR analysis. Notably, in vitro biocompatibility assay using DAPI
      and Rhodamine 123 staining demonstrated that the proliferation of NIH3T3
      fibroblast cells was better for CSCE when compared to the Col and CS scaffolds.
      In vivo wound healing experiments with full-thickness excision wounds in wistar
      rat model demonstrated that the wounds treated with CSCE showed accelerated
      healing with enhanced collagen deposition when compared to wounds treated with
      Col and CS scaffolds, and these studies substantiated the efficacy of CSCE
      scaffold for treating wounds.

PMID- 30184755
TI  - Designing of membrane-active nano-antimicrobials based on cationic copolymer
      functionalized nanodiamond: Influence of hydrophilic segment on antimicrobial
      activity and selectivity.
AB  - Designing cationic nano-antimicrobial is a promising solution for combating drug
      resistant microbes. In this work, hydrophilic cationic copolymer was applied for
      the surface functionalization of nanodiamonds (NDs) aiming at developing a highly
      membrane-active nano-antibacterial agent with satisfactory selectivity. As a
      result, after functionalization, the increased repulsive forces within NDs and
      interaction with solvent molecular network made the heavily aggregated pristine
      NDs break down into tiny nanoparticles with particle size ranging from 10 to 100
      nm. The improved hydrophilicity and enlarged surface area endowed QND-H5 and QND
      H10 a powerful bactericidal capability toward both of Gram-negative Escherichia
      coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus). In the
      further bactericidal assessment, it was also demonstrated that the formation of
      hydrogen bonding between the 2-hydroxyethyl methacrylate (HEMA) side chains and
      lipid head groups of bacterial membrane also contributed to the enhanced
      bactericidal ability. Field emission scanning electron microscopy analysis
      confirmed that as-prepared nano-hybrid acted bactericidal ability via physical
      nature of outer membrane and cytoplasmic membrane-separating destruction
      mechanism toward E. coli, which may derive from the hydrogen bonding ability,
      making them more effective toward bacterial. More importantly, it was found that
      with just 10% of HEMA, QND-H10 displayed good selectivity toward bacteria over
      mammalian cells as shown by the high HC50 values with relatively low MIC values,
      suggesting the great potential application in medical fields. These results
      indicate that hydrogen bonding is an important element to achieve the desired
      high antibacterial activity and selectivity, particularly when cationic nano
      antibacterial agents are required for medical application.

PMID- 30184756
TI  - Gadolinium borate and iron oxide bioconjugates: Nanocomposites of next generation
      with multifunctional applications.
AB  - The systematic investigations concerning the bioconjugation of GdBO3-Fe3O4
      nanocomposite and their in vitro biocompatibility with cancer cell lines are
      reported. The nanocomposites were prepared hydrothermally from magnetite (Fe3O4),
      borax or boric acid and a Gd3+ salt. Bioconjugation processes were performed with
      citric acid and fluorescein isothiocyanate-doped silica, followed by the
      treatment with folic acid. Overall, the procedure involved "bare or PEGylated
      Fe3O4 as the magnetic core" and "vaterite- or triclinic-type of GdBO3 as the
      surface borate layer" for comparative evaluation of the results. The successful
      vectorization of the nanocomposite particles was demonstrated by quantitative and
      qualitative analytical data. All bioconjugates displayed soft ferromagnetic
      properties and negative zeta potential values that are appropriate for biological
      applications. The 10B and 157Gd contents were ca. 1014 atom/MUg making them
      promising agents for BNCT, GdNCT and the combined GdBNCT. The Gd/Fe molar ratios
      (0.27-0.63) provided the capability for T1- or dual (T1 + T2) magnetic resonance
      imaging (MRI). In vitro studies were conducted to investigate the efficiency of
      targeted FA-conjugated versus non-FA conjugated nanoformulations on Mia-Pa-Ca-2,
      HeLa and A549 cells. Fluorescence microscopy and flow cytometry data unveiled the
      essential role of the zeta potential competing with folate targeting in the
      uptake mechanism. The bioconjugated nanoplatforms of GdBO3-Fe3O4 composite,
      introduced herein, proved to have potential features of next generation agents
      for magnetically targeted therapy, fluorescence imaging, magnetic resonance
      imaging/diagnosis and Neutron Capture Therapy.

PMID- 30184757
TI  - Preparation of hydroxyapatite porous scaffold from a 'coral-like' synthetic
      inorganic precursor for use as a bone substitute and a drug delivery vehicle.
AB  - A novel surfactant free hydrothermal method was developed for the preparation of
      large hydroxyapatite scaffolds. Synthetic calcium carbonate (calcite) was used as
      the starting material which when mixed with an inorganic setting solution
      containing phosphoric acid and sodium hydroxide forms the porous precursor body
      with pore size 20-700 MUm. The porous precursor body was then hydrothermally
      converted to hydroxyapatite scaffolds when treated in basic phosphate solution of
      pH 10.5 at 150  degrees C and 15 bar pressure maintaining the structural
      stability and integrity. X-ray diffraction and the Fourier transform infrared
      spectroscopy confirmed that the developed material consist of single phase
      crystalline hydroxyapatite. Surface morphology and microstructures were studied
      using scanning electron microscopy and porosity was evaluated by micro CT
      analysis. The cell material interactions evaluated by cell viability assays and
      live cell staining methods confirmed the cell compatibility. The drug release
      study at physiological pH implied that the developed materials could be promising
      in sustained long-term release. The results emerged have shown that the
      hydrothermal conversion of inorganic coral-like precursor is effective to produce
      porous bioactive hydroxyapatite scaffolds for bone regeneration as well as drug
      delivery vehicles for the treatment of infectious bone diseases such as
      osteomyelitis.

PMID- 30184758
TI  - Synthesis and characterization of paclitaxel-imprinted microparticles for
      controlled release of an anticancer drug.
AB  - In this study, novel molecularly imprinted polymer (MIP) microparticles
      containing methacryl polyhedral oligomeric silsesquioxane (M-POSS) were
      synthesized through the RAFT precipitation polymerization (RAFTPP) method using
      paclitaxel (PTX) as the templates. During the course of this investigation,
      methacrylic acid (MAA) was used as the functional monomer, while ethylene glycol
      dimethacrylate (EGDMA) was utilized as a cross-linker. The effects of different
      molar ratios of M-POSS on the microparticles were characterized. The obtained MIP
      microparticles were confirmed by FT-IR and TGA-DSC. The results of SEM showed
      regular spherical-shaped MIP microparticles with diameters around 170-490 nm. The
      PTX loading quantity was closely correlated with the content of M-POSS, and the
      MIP microparticles showed a satisfactory affinity to PTX with high drug loading
      (17.1%) and encapsulation efficiency (85.5%). Moreover, these MIP microparticles
      were sensitive to pH, and consequently the release rates of PTX at pH 5 were much
      faster than those at pH 7 due to the acid cleavage of the hydrogen bonds. In
      addition, the results from release experiments of the MIP microparticles showed a
      very slow and controlled release of PTX, which heralded promising potential as a
      carrier for PTX delivery in cancer therapy.

PMID- 30184760
TI  - Fabrication of a new superparamagnetic metal-organic framework with core-shell
      nanocomposite structures: Characterization, biocompatibility, and drug release
      study.
AB  - The Superparamagnetic CoFe2O4NPs@Mn-Organic Framework core-shell nanocomposites
      that had potential application in targeted drug-delivery were synthesized by
      layer to layer method. The structure and composition of the obtained microspheres
      were characterized by SEM, TEM, DLS, XRD, VSM, FTIR, and TG analysis. Results
      showed that the structures have a high degree crystalline, high temperature
      stability, magnetics and core-shell nanocomposites. Therefore, it is an excellent
      candidate for drug delivery systems. Afterwards, Daunorubicin (as a drug model)
      was laden in the MOFs by a Simple stirring. For comparison of magnetic properties
      of MOFs for drug delivery, an external magnetic field applied to the plate to
      evaluate the efficiency. The external magnetic field significantly increases anti
      tumor activity of formulation (drug+ MOFs). The results showed that MOFs are
      biocompatible, which endue MOFs great potential in targeting drug-delivery
      systems with enhanced efficiency.

PMID- 30184759
TI  - Polysaccharide and poly(methacrylic acid) based biodegradable elastomeric
      biocompatible semi-IPN hydrogel for controlled drug delivery.
AB  - Nanoparticles embedded semi-interpenetrating (semi-IPNs) polymeric hydrogels with
      enhanced mechanical toughness and biocompatibility could have splendid biomedical
      acceptance. Here we propose poly(methacrylic acid) grafted polysaccharide based
      semi-IPNs filled with nanoclay via in situ Michael type reaction associated with
      covalent crosslinking with N,N-methylenebisacrylamide (MBA). The effect of
      nanoclay in the semi-IPN hydrogel has been investigated which showed significant
      improvement of mechanical robustness. Meanwhile, the hydrogels showed reversible
      ductility up to 70% in response to cyclic loading-unloading cycle which is an
      obvious phenomenon of rubber-like elasticity. The synthesized semi-IPN hydrogel
      show biodegradability and non-cytotoxic nature against human cells. The live-dead
      assay showed that the prepared hydrogel is a viable platform for cell growth
      without causing severe cell death. The in vitro drug release study in
      psychological pH (pH = 7.4) reveals that the controlled drug release phenomena
      can be tuned by simulating the environment pH. Such features in a single hydrogel
      assembly can propose this as high performance; biodegradable and non-cytotoxic 3D
      scaffold based promising biomaterial for tissue engineering.

PMID- 30184761
TI  - beta-Cyclodextrin engineered gamma-Fe2O3@ hydroxyapatite nanocomposite as a novel
      scaffold for the synthesis of phenacyl derivatives.
AB  - Magnetic hydroxyapatite (HAp) is being widely investigated for various
      applications in medical engineering and nanocomposite for transformation
      reaction. The present work describes an efficient procedure for the synthesis of
      phenacyl derivatives employing a novel, green and magnetically retrievable
      nanocomposite via the grafting of beta-cyclodextrin moieties on the magnetic
      hydroxyapatite surface, gamma-Fe2O3@HAp-CD. The structure and composition of the
      nanocomposite was performed by different methods and analyzed by Infrared
      Spectroscopy (FT-IR), Field Emission Scanning Electron Microscopy (FE-SEM),
      transmission electron microscopy (TEM), Thermo-Gravimetric Analysis (TGA), X-ray
      diffraction (XRD), energy dispersive X-ray spectroscopy (EDS) and Brunauer Emmett
      Teller (BET) and vibrating sample magnetometry (VSM). Our results indicate that
      conjugation with beta-CD improves the catalytic activity in the reaction.

PMID- 30184762
TI  - A photoresponsive surface molecularly imprinted polymer shell for determination
      of trace griseofulvin in milk.
AB  - A new photoresponsive surface molecularly imprinted polymer shell (PMIPS) was
      developed for determination of trace griseofulvin from milk. The PMIPS was
      prepared by surface imprinting technique using poly(styrene-co-methacrylic acid)
      (PS-co-PMMA) microspheres as the sacrificial substrate, griseofulvin as the
      template, a photoresponsive azobenzene derivative 4-((4
      (methacryloyloxy)phenyl)diazenyl)-3,5-dimethyl benzenesulfonic acid as the
      functional monomer, and triethanolamine trimethacrylate as the cross-linker. The
      PMIPS was obtained after the removal of the sacrificial PS-co-PMMA core from the
      surface imprinted core-shell microspheres, PS-co-PMAA@PMIP. Compared with PS-co
      PMAA@PMIP, PMIPS displayed better properties such as higher surface area and pore
      volume, rapid photo-isomerization rate, and higher adsorption capacities,
      specific binding constant and binding density. The PMIPS could efficiently detect
      griseofulvin in complex samples such as milk.

PMID- 30184763
TI  - Optimization of strontium aluminate-based mechanoluminescence materials for
      occlusal examination of artificial tooth.
AB  - This work presents a novel approach for evaluating the occlusal examination of
      artificial tooth based on the mechanoluminescence (ML) materials. The rare earth
      doped strontium aluminate (SrAl2O4: Eu2+, Dy3+; SAOED) was chosen as the ML
      material, which was further composited with the commercial denture base resin
      (DBR) to determine its feasibility for the mechanics analysis of artificial tooth
      occlusion. To eliminate negative factors for occlusal analysis, SAOED was first
      optimized to exhibit a rapid decay of afterglow and enhanced ML intensity. The
      luminescent characterizations of the SAOED/DBR composites suggest DBR is a
      desirable elastic-supporter for nondestructive ML generation. Furthermore, the
      introduction of SAOED improved the mechanical performance of DBR, and its
      biocompatibility was maintained at the same time. These results suggest the
      feasibility of the idea to detect the mechanics in occlusal examination of
      artificial tooth based on ML. The bright and sensitive ML from the constructed
      standard artificial tooth models could guide clinicians to purposefully adjust
      the occlusal surface until a balanced occlusion established.

PMID- 30184764
TI  - In-vivo sustained release of nanoencapsulated ferulic acid and its impact in
      induced diabetes.
AB  - Diabetes mellitus (DM) is one of the most common lifestyle diseases, caused due
      to endocrine disorder. DM is commonly associated with hyperglycemia, a condition
      which is generally followed by an overproduction of free radicals leading to
      tissue oxidative stress. Currently, the focus of medical fraternity lies in
      developing therapeutic drugs based on natural origin in order to reduce the
      hyperglycemia associated toxicity. Ferulic acid (FA) is a ubiquitous
      hydroxycinnamic acid displaying an array of therapeutic properties, including
      anti-diabetic effect which could be attributed to its potent antioxidant
      capacity. However, due to low bioavailability and clinical efficacy of FA, its
      biomedical applications remained limited. In the present study, FA encapsulated
      chitosan nanoparticles (FANPs) were synthesized through ionotropic gelation
      process with an aim to enhance FA bioavailability. The plasma release and urinary
      excretion profiles of FANPs were compared with that of free FA using healthy
      Wistar albino rats as a model system. The encapsulated FA displayed extended
      plasma retention time and maximum plasma concentration was recorded at 60 min
      which implied four times enhancement of Tmax compared to free FA. The elimination
      of compound from the animal body also displayed a similar pattern where the peak
      urinary excretion of FA from nanoformulations. FANPs were also tested for their
      anti-hyperglycemic effects in streptozotocin (STZ) induced diabetes in Wistar
      albino rats and were found to attenuate the diabetes-associated symptoms. FANPs
      caused an enhancement in body weight, decrease in blood glucose level along with
      a regulatory effect on blood lipid profile of diabetic rats. Positive impact of
      FANPs in improving the hyperglycemic condition prevalent in diabetic rats might
      provide new avenues for the treatment of DM and help avoid secondary
      complications associated with the synthetic drugs.

PMID- 30184765
TI  - Chitosan based copolymer-drug conjugate and its protein targeted polyelectrolyte
      complex nanoparticles to enhance the efficiency and specificity of low potency
      anticancer agent.
AB  - The effective delivery of low potency anticancer drug is a major challenge. The
      present study introduces the novel chitosan-polylactic acid (CS-PLA)-drug
      conjugate and its transferrin receptor targeted polyelectrolyte complex
      nanoparticles (PEC Nps), encapsulating free drug to increase its potency and
      specificity. The model drug curcumin (CR) was used and incorporated in this
      system in both conjugated and encapsulated form. The synthesis of CS-PLA-CR
      copolymer was confirmed by 1H NMR, FTIR, UV-visible spectrum, DSC thermogram and
      zeta potential. Further, the nanoparticles engulfing free CR, with average 340 nm
      particle sizes, were prepared through simple ionic gelation technique utilizing
      positive charges on copolymer by polyanion sodium alginate (CS-PLA-CR/SA PEC
      Nps). The prepared Nps showed the high CR content of over 92% with extended
      period of CR release (60% and 85% at pH 7.4 and 5 respectively even after 8
      days). The results were compared with the unmodified CS (without PLA) as a
      control to understand the effect of PLA side chain. Transferrin (Tf) conjugation
      on PEC Nps displayed superior cytotoxicity and cellular uptake compared to non
      targeted Nps on MCF-7 cell line. Thus, CR loaded Tf-CS-PLA-CR/SA PEC Nps may
      provide an efficient and targeted delivery for cancer treatment.

PMID- 30184766
TI  - Analysis of the mechanical effects of defect shape on damage evolution of
      articular cartilage under rolling load.
AB  - To study the mechanical effects of defect shape on the damage evolution of knee
      cartilage and find the causes of fragments, so as to obtain damage evolution
      rules and determine the most appropriate shape used in a clinical repair. A
      porous viscoelasticity fiber-reinforced 2D numerical model with different micro
      defect shapes was established which considered the depth-dependent Young's
      modulus, fiber distribution, porosity and permeability. The stress-strain
      relationship, interstitial hydraulic and interstitial flow velocity was obtained
      under rolling load. The results showed that damage developed at the bottom corner
      of the defect, preferentially deep within the cartilage tangential to the fibers
      direction, and then extended to the surface along adjacent fibers, finally
      forming fragments. In the early stages of damage, the shear stress and
      interstitial flow velocity within cartilage with a rectangular cross-sectional
      defect were the lowest, while interstitial hydraulic pressure was the highest,
      followed by 100 degrees  trapezoid and semicircle, and finally 80 degrees 
      trapezoid defects. In the later stage of damage, the results were very similar.
      The shear strain, interstitial flow velocity and interstitial hydraulic pressure
      decreased with increasing defect depth. Therefore, defect shape only affected
      damage evolution in the early stages. The fragments in cartilage were the result
      of the damage evolution which sizes were correlated with the initial defect
      depth. The damage velocity of cartilage with a rectangular section-incision was
      the slowest. Finally, we concluded that cylindrical incisions are optimal in
      clinical surgery. These results provide a theoretical basis for the clinical
      interpretation of pathological degeneration and repair therapy.

PMID- 30184767
TI  - Carbon nanoparticles suspension injection for the delivery of doxorubicin:
      Comparable efficacy and reduced toxicity.
AB  - Drug delivery systems for doxorubicin (DOX) have attracted tremendous interest
      nowadays for the improved efficacy and/or reduced toxicity. Due to the aromatic
      structures and hydrophobic domains, carbon nanoparticle suspension injection
      (CNSI), a clinical applied reagent for lymph node mapping, strongly adsorbs DOX
      and holds great potential in cancer therapy. Herein, we evaluated the therapeutic
      effects of CNSI-DOX to establish its delivery applications for cancer drugs. CNSI
      adsorbed DOX from solution quickly after the mixing, and the release of DOX from
      CNSI followed a pH-dependent way. CNSI-DOX and free DOX had nearly identical
      inhibitive effects on cancer cells, while the vehicle CNSI was nontoxic. CNSI-DOX
      largely prolonged the life span of ascites tumor bearing mice after the
      intraperitoneally injection and the ascites weights showed significant decreases.
      CNSI-DOX also inhibited the growth of subcutaneous xenografts following the same
      administration route. The therapeutic efficacy of CNSI-DOX was similar to that of
      free DOX in ascites tumor model, but slightly lower in subcutaneous xenografts
      model. The advantage of using CNSI was majorly reflected by the reduced toxicity
      of DOX according to the bodyweight changes, serum biochemical indicators and
      histopathological observations. The LD50 (median lethal dose) value of CNSI-DOX
      was 43.8 mg/kg bodyweight, nearly three times of that of free DOX (15.2 mg/kg
      bodyweight). Our results suggested that CNSI might be used for DOX delivery
      through "off label" use to benefit the patients immediately.

PMID- 30184768
TI  - Pharmacological application of barium containing bioactive glass in gastro
      duodenal ulcers.
AB  - Peptic ulcer is prevalent in about 4% of the world population and nearly 10% of
      people have been affected by peptic ulcer at some point in their life. Therefore,
      there is a need for newer efficient and safe anti-ulcer agents. In the present
      strategy, we have prepared a novel bioactive glass containing 1.3 mol% of barium
      oxide (BaBG) and evaluated its antiulcer potential in gastroduodenal ulcer
      models. Prophylactic effect of BaBG pretreatment was evaluated for 5 days in
      ethanol, aspirin and pyloric ligation-induced gastric ulcer and cysteamine
      induced duodenal ulcer models. Repeated treatment of 10 days of BaBG was
      evaluated in the healing ulcer model of acetic acid. BaBG significantly reduced
      the ulcerative damage against all the five tested ulcer models. Scanning electron
      microscope (SEM) images have shown that BaBG forms a physical protective barrier
      over the gastro-duodenal epithelium cell. In the pyloric-ligation, ethanol and
      aspirin models, BaBG showed significantly increased in gastric pH, indicating
      antacid like activity. BaBG treatment significantly increased cell proliferation
      in the pyloric model. Thus, BaBG mediates antiulcer action by forming a
      protective physical barrier against harsh luminal factors, acid neutralization
      and cell proliferation.

PMID- 30184769
TI  - Lanthanum-silicate-substituted apatite synthesized by fast mechanochemical
      method: Characterization of powders and biocoatings produced by micro-arc
      oxidation.
AB  - Lanthanum-silicate substituted apatite with equal concentrations of the
      substituents in the range of 0.2-6.0 mol were produced by a fast method -
      mechanochemical synthesis. This method makes it possible to synthesize a
      nanosized single-phase product by activating reaction mixtures containing CaHPO4,
      CaO, La(OH)3 and SiO2.H2O for 25-30 min in AGO-2 and AGO-3 planetary mills. The
      structure of the apatites was investigated by the FTIR and XRD methods. It was
      found that the synthesized samples with substituent concentrations up to 2 mol
      are substituted oxy-hydroxyapatites, at higher concentrations, they are
      substituted oxyapatites. The mechanochemically synthesized apatite with a
      substituent concentration of 0.5 mol was used for depositing biocoatings on
      titanium substrates by the micro-arc oxidation method. The structure of the
      coatings is mainly amorphous. In vitro biological tests demonstrated high
      biocompatibility of the coatings and the absence of cytotoxic action on
      mesenchymal stem cells.

PMID- 30184770
TI  - Dual layer collagen-GAG conduit that mimic vascular scaffold and promote blood
      vessel cells adhesion, proliferation and elongation.
AB  - A dual layer conduit, which consists of collagen I-hyaluronic acid (Col-HA,
      external layer) and collagen I-heparin (Col-HP, inner layer), has been developed.
      This conduit not only meets the structural requirement of nature blood vessel,
      but also presents favourable mechanical performance after crosslinking via EDC.
      In addition, its biological properties are evaluated through culturing with
      fibroblast cell (Cos-7) on Col-HA surface and vascular endothelial cell (HMEC) on
      Col-HP layer. Results demonstrate that the conduit can support Cos-7 and HMEC
      adhesion, proliferation and elongation on respective side. This dual layer
      conduit would be a new choice of artificial vascular scaffold and improve blood
      vessel regeneration for tissue engineering.

PMID- 30184771
TI  - Synthesis and biological evaluation of redox/NIR dual stimulus-responsive
      polymeric nanoparticles for targeted delivery of cisplatin.
AB  - Functional drug delivery systems enabling various favorable characteristics
      including specific targets, efficient cellular uptake and controllable release.
      At present work, a folate and cRGD dual modified nanoparticles based on NIR light
      and glutathione dual stimuli-responsive release system was successfully prepared
      and which simultaneously deliver cisplatin and ICG to tumor sites to enhance
      controllability. The prepared nanoparticles showed a stable uniform spherical
      morphology of 77.59 nm particle size range in PBS (pH = 7.4, 25  degrees C) and
      the encapsulated cisplatin were rapidly released in acidic environment especially
      added glutathione (GSH) and NIR irradiation. Moreover, the prepared nanoparticles
      can be efficiently internalized by tumor cells through the enhanced dual targeted
      ligands (folate and cRGD) for ICG imaging. The cytotoxicity assays showed that
      the cells viability decreased to 1.95% (SGC-7901) when been exposed to NIR light,
      and which further decreased to 1.25% in MCF-7 cells. Thus, the prepared
      nanoparticles showed excellent performance for photothermal conversion therapy of
      tumor cells and especially on human breast tumor cells. Our research highlights
      the great potential of stimuli-responsive smart nanoparticles in biomaterial and
      nano-biomedicine.

PMID- 30184772
TI  - Ag-carried CMC/functional copolymer/ODA-Mt wLED-treated NC and their responses to
      brain cancer cells.
AB  - The subject of this work is synthesis and characterization of novel
      multifunctional nanocomposite (8/2A-NC) consisting (1) carboxymethyl cellulose
      (CMC) as a matrix biopolymer and poly (maleic acid-alt-acrylic acid) as a
      reactive synthetic partner matrix polymer; (2) octadecyl amine montmorillonite
      (ODA-MMT) reactive organoclay provide intercalated silicate layers structures and
      aqueous colloidal dispersing medium, and MMT as carriers and targeting agents for
      anticancer agents in drug delivery systems, respectively. ODA as a intercalated
      surfactant finely dispersed 8/2A NC and its compatibility with matrix polymers
      via the interfacial polarization (complexing) and functionalization of matrix
      polymers by amine (ODA) and carboxylic acids from both the CMC and copolymer; (3)
      silver nanoparticles (AgNPs) as in-situ generated onto matrix polymers with
      unique nano-size and morphology parameters was synthesized. Important material
      science and bioengineering aspects of these investigations included (a) novel
      approach in synthetic pathways; (b) effects of physical and chemical structural
      rearrangements; (c) effects of Light Emitting Dioda (LED)-treatment on the FT-IR
      spectra, XRD reflection parameters, SEM-TEM morphology and nano-size and diameter
      distribution of AgNPs onto matrix polymers; (d) positive effect of LED-treatment
      of 8/2A nanocomposite and its response to the MIAPaCa-2 and U87 human brain
      cancer cell lines were evaluated. Novel 8/2A-NC multifunctional drug consisting
      unique positive, intercalating and encapsulated core-shell morphology structures,
      nano-size (5.6 nm) and narrow diameter distribution (94%) of AgNPs onto matrix
      polymers [silver NPs (0.25%) in 8/2A NC (25%)] with highest volume of contact
      area compared with used cancer micro-cells show lowest cell viability as an
      excellent anticancer platform. 8/2A-NC is a novel multifunctional drug with
      intercalating and encapsulated core-shell morphology structures consisting of
      positively charged, non-randomly distributed AgNPs with a large contact area and
      low diameters (5-6 nm). The anticancer properties of (This factor is not
      conformed experimentally in work) this drug can be explained by the following
      structural factors: 8/2A-NC contains a combination of active sites from
      protonated hydroxyl, carboxyl and amine groups; Ag+-cations and ODA-MMT with high
      physical and chemical surface areas. We suggest this material be further explored
      for anti-cancer testing.

PMID- 30184774
TI  - A novel simple biosensor containing silver nanoparticles/propolis (bee glue) for
      microRNA let-7a determination.
AB  - A novel sensitive electrochemical sensor for microRNAlet-7a detection in normal
      serum samples, hepatocellular carcinoma patients and human liver cancer cells,
      has been excellently synthesized. The sensor constructed of carbon paste (CP)
      amended with silver nanoparticles (AgNPs) and extracted propolis (bee glue). The
      AgNPs/P modified carbon paste electrode (APCPE) displayed a high electrocatalytic
      activity in a Britton Robinson (BR) buffer (pH = 7.4). The techniques utilized to
      prepare this work are square wave voltammetry (SWV) and electrochemical impedance
      spectroscopy (EIS). Surface characteristics were achieved using scanning (SEM),
      Fourier-transform infrared spectroscopy (FTIR), Spectrophotometer, transmission
      (TEM) electron microscope, energy dispersive X-ray analysis (EDX) and elemental
      mapping (EM) techniques. Under optimal conditions, the suggested sensor exhibits
      good rapid and sensible response reaching a very low detection limit of 10-3
      femtomolar.

PMID- 30184773
TI  - pH-sensitive tangeretin-ZnO quantum dots exert apoptotic and anti-metastatic
      effects in metastatic lung cancer cell line.
AB  - Most cancer patients die as a consequence of distant metastases, which are
      frequently unresponsive to cancer therapy. This study focuses on the anti
      tumorigenic and anti-metastatic properties of tangeretin-zinc oxide quantum dots
      (Tan-ZnO QDs) against the NCI-H358 cell line. Tan-ZnO QDs are pH-sensitive and
      capitalize on the acidic pH maintained in the tumor microenvironment; therefore,
      targeted drug delivery is directed specifically to cancer cells, leaving the
      normal cells less affected. Tan was loaded into synthesized ZnO QDs, and drug
      loading was analyzed using Fourier transform infrared (FTIR) spectroscopy and
      ultraviolet-visible (UV-Vis) spectrometry. Crystalline phase and particle size
      were measured using transmission electron microscopy (TEM) and X-ray diffraction
      (XRD). Drug release was evaluated in buffered solutions with differing pH for up
      to 15 h. The results confirmed stable drug release (80%) in an acidic pH. Tan-ZnO
      QDs induced significant cytotoxicity in NCI-H358 metastatic cells, while not
      markedly affecting HK-2 human normal cells. Morphology of treated H358 cells
      analyzed via atomic force microscopy (AFM) showed an increased surface roughness
      and pores. Further, the number of terminal deoxynucleotidyl transferase dUTP nick
      end labeling (TUNEL)-positive cells increased after treatment with Tan-ZnO QDs.
      DNA fragmentation was also induced after treatment with increasing concentrations
      of Tan-ZnO QDs in H358 cells. We also confirmed regulation of apoptosis via
      expression levels of Bax and Bcl-2 proteins; G2/M phase cell cycle arrest was
      observed. Additionally, cell proliferation and migration drastically decreased,
      and cell invasion and migration, hallmarks of metastasis, were significantly
      inhibited in H358 cells. Matrix metalloproteinase (MMP)2 and MMP9, markers of
      metastasis, as well as vascular endothelial growth factor (VEGF), a marker of
      angiogenesis, were significantly downregulated upon treatment with Tan-ZnO QDs.
      In conclusion, our novel formulation destabilized H358 cells by using its acidic
      tumor microenvironment, thereby regulating cell apoptosis, proliferation, and
      metastatic properties.

PMID- 30184775
TI  - Comparison of adsorption and conjugation of Herceptin on poly(lactic-co-glycolic
      acid) nanoparticles - Effect on cell internalization in breast cancer cells.
AB  - Surfaces of nanoparticles with are commonly modified to enhance the targeting
      effect. In this study, we performed surface modifications of docetaxel (DTX)
      loaded poly(lactic-co-glycolic acid) nanoparticles (PNPs) with Herceptin(r) (HCT)
      to improve the internalization and cytotoxicity in breast cancer cells. The PNPs
      were prepared with surfactant, poly(ethylene-alt-maleic anhydride) (PEMA),
      including a number of carboxyl groups for conjugation. Three types of PNPs were
      prepared via different methods such as adsorption, charged adsorption, and bio
      conjugation. The PNPs were evaluated in terms of physical properties, stability,
      cellular uptake and cytotoxicity. The docetaxel-loaded PNPs with HCT were
      successfully surface-modified with mean particle sizes of 338.4 +/- 59.8 nm (DTX
      PNPs), 353.9 +/- 67.5 nm (HCT-A-DTX-PNPs), 544.8 +/- 301.7 nm (HCT-C-DTX-PNPs),
      and 499.1 +/- 71.9 nm (HCT-B-DTX-PNPs). Cellular uptake of HCT-B-PNPs was 5.0-,
      4.4-, and 4.6-fold higher than that of PNPs in BT-474, SK-BR-3, and MCF-7 cells,
      respectively, at 2 h. At 40 MUg/mL, HCT-B-DTX-PNPs showed a higher cytotoxicity
      toward BT-474, SK-BR-3, and MCF-7 cells than the other formulations. In
      conclusion, HCT-B-DTX-PNPs were found to possess a higher affinity for breast
      cancer cells and induce a stronger cytotoxicity than that of other PNPs.

PMID- 30184776
TI  - Preparation of sulfur nanoparticles and their antibacterial activity and
      cytotoxic effect.
AB  - Sulfur nanoparticles (SNPs) were prepared using sodium thiosulfate and
      hydrochloric acid, and the UV-visible spectrum showed the formation of
      nanoparticulate sulfur. The SNPs were characterized by UV-visible
      spectrophotometer, transmission electron microscope (TEM), energy dispersive X
      ray spectroscopy (EDX), X-ray photoelectron spectroscopy (XPS), X-ray diffraction
      (XRD), and thermogravimetric analysis (TGA). The antibacterial activity and the
      cytotoxic effects of the SNPs on the human lung carcinoma (A549), mouse colon
      carcinoma (CT26), Caco-2, and human fibroblast (CCD-986sk) cells were tested. In
      addition, the inhibitory effect of the SNPs on the cancer cell migration was
      evaluated. The SNPs capped with chitosan (SNP2) exhibited strong antibacterial
      activity against Escherichia coli and Staphylococcus aureus. SNP2 also
      effectively inhibited the proliferation and migration of cancer cells with
      minimal toxic effect on normal cells. SNP2 therefore has potential for medical
      applications, including those used as antibacterial and chemotherapeutic agents.

PMID- 30184777
TI  - A novel strategy for fabrication of fluorescent hydroxyapatite based polymer
      composites through the combination of surface ligand exchange and self-catalyzed
      ATRP.
AB  - A novel and facile strategy that combination of surface ligand exchange and photo
      initiated atom transfer radical polymerization (ATRP) has been developed for the
      preparation of fluorescent hydroxyapatite (HAp) based polymer composites, which
      were utilized for biological imaging applications. In particular, the photo
      initiated ATRP not only inherited advantages of traditional ATRP but also
      overcome its deficiencies such as high energy consumption, transition metal
      contamination and long reaction time. In this method, a hydrophilic and
      biocompatible PEGMA was introduced to enhance the hydrophilic and
      biocompatibility of HAp nanocomposites. Simultaneously, the HAp-poly(PEGMA-co
      AcFl) composites are endowed with bright green fluorescence by grafting with AcFl
      on the surface via copolymerization. The physicochemical properties of HAp
      poly(PEGMA-co-AcFl) composites were characterized by a series of methods in
      detail. Results confirmed that HAp-poly(PEGMA-co-AcFl) composites possess
      controlled size and morphology, high water dispersibility and strong
      fluorescence. The cell viability and cell uptake behavior demonstrated that HAp
      poly(PEGMA-co-AcFl) composites present low toxicity and can be potentially used
      for biological imaging. Taken together, we have developed a facile and efficient
      method for the fabrication of fluorescent HAp composites with desirable
      physicochemical and biological properties.

PMID- 30184778
TI  - Catechol-rich gelatin hydrogels in situ hybridizations with silver nanoparticle
      for enhanced antibacterial activity.
AB  - Recently, the interest in antimicrobial hydrogels with impregnated antibacterial
      agents has significantly increased because of their ability to combat infection
      in biomedical applications, including wound management, tissue engineering, and
      biomaterial surface coating. Among these antibacterial reagents, silver
      nanoparticles (AgNP) show good antibacterial activity against both gram-negative
      and gram-positive bacteria, including highly multi-resistant strains. However,
      the entrapment of AgNP within a hydrogel matrix is often associated with toxicity
      issues because of the use of chemical reductants (e.g., commonly sodium
      borohydride), burst leaching, or unwanted agglomeration of AgNP in the absence of
      surfactants or stabilizers. In this study, we present catechol-rich gelatin
      hydrogels with in situ hybridization of AgNP for enhanced antimicrobial
      activities. AgNP were formed through a redox reaction between silver ions and the
      catechol moieties of a gelatin derivative polymer, without the addition of any
      chemical reductants. The AgNP with an average size of 20 nm were entrapped within
      hydrogel matrices and showed sustained release from the hydrogel matrix (8.7% for
      14 days). The resulting hydrogels could kill both gram-negative and gram-positive
      bacteria, depending on the amount of AgNP released from the hydrogels and did not
      have a significant influence on mammalian cell viability. We believe that our
      catechol-rich hydrogels in situ hybridizations with AgNP have great potential for
      biomedical applications, such as wound management and surface coating, because of
      their excellent antibacterial activities and biocompatibility.

PMID- 30184779
TI  - Fast dissolving moxifloxacin hydrochloride antibiotic drug from electrospun
      Eudragit L-100 nonwoven nanofibrous Mats.
AB  - Antimicrobial electrospun nonwoven Eudragit L-100 nanofibrous mats containing
      Moxifloxacin hydrochloride (MOX-HCL) were fabricated for fast dissolving drug
      delivery systems (DDSs) associated with wound infection. The morphological
      characterization of nanofibers using ESEM revealed that the average diameter of
      non-woven nanofibrous mats ranges 200-600 nm. The nanofiber showed cylindrical
      shape with crack on the surface. Differential scanning calorimetric (DSC) and
      Wide Angle X-ray diffraction (WAXRD) demonstrate that the drug exists in an
      amorphous state in the nanofibers. Nanofibrous mats were also tested for
      mechanical strength, contact angle, swelling assay, haemolysis and disintegration
      test. In vitro disintegration tests demonstrated that the dissolution of Eudragit
      L-100 fiber mats was within 25 s which was higher compared to the pure drug. The
      Eudragit nanofibers showed pH-dependent drug release profiles, with slow release
      at pH 1.2 and burst release (around 30 s) at pH 6.8. The in-vitro quantitative
      and qualitative antimicrobial assay showed that the developed Eudragit L-100
      nanofibrous mats with MOX-HCL concentration of 1%, 5% and 15 wt% exhibited
      antibacterial activities against both gram positive (Staphylococcus aureus) and
      gram negative (Escherichia coli) bacteria. The in-vitro cytotoxicity assay using
      mouse fibroblast NIH/3T3 cells demonstrated significant biocompatibility of
      nanofiber mats. As per the results of biological evaluation, Eudragit L-100
      nanofibrous mats with 1wt% MOX-HCL could be a suitable substrate for biomedical
      applications. Eudragit L-100 nanofibrous mats containing Moxifloxacin
      hydrochloride (MOX-HCL) showed immediate DDSs for localized drug release in the
      wound infection at slightly acidic or alkaline conditions where faster drug
      release rate is required for wound healing.

PMID- 30184780
TI  - Chitosan/gelatin as a new nano-carrier system for calcium hydroxide delivery in
      endodontic applications: Development, characterization and process optimization.
AB  - The main aim of this study is preparation, optimization and in vitro
      characterization of Chitosan/Gelatin nano-carriers (NCs) for calcium hydroxide
      (CH) to improve its therapeutic potential. The designed system can be used in the
      endodontic applications demanding a sustained release of calcium and hydroxyl
      ions. Modeling and optimization of CH loaded polymeric NCs were performed using
      response surface methodology (RSM) based on central composite surface statistical
      design. The effect of Chitosan concentration (0.1-1% w/v), Gelatin concentration
      (0.1-1% w/v) and CH concentration (0.05-0.4% w/v) on the particle size,
      polydispersity index (PDI), drug loading (DL) and encapsulation efficiency (EE)
      of CH loaded polymeric NCs were investigated. Optimized CH loaded polymeric NCs
      formulation which obtained using RSM showed spherical and smooth surface with a
      particle size of 292 nm, PDI of 0.32, DL of 88.8% and EE of 99%. Optimized
      formulation was evaluated for in vitro calcium ion release in phosphate buffer
      solution (PBS) at pH 7.4 for 14 days. The presence of hydrogen bonding and some
      intermolecular interactions between Chitosan/Gelatin polymeric materials were
      confirmed using Fourier transform infrared (FTIR) analysis. These interactions
      enable Chitosan/Gelatin NCs to load CH and maintain sustained release of Calcium
      ions from CH during experimental period.

PMID- 30184781
TI  - Triggered release of paclitaxel from magnetic solid lipid nanoparticles by
      magnetic hyperthermia.
AB  - We developed a magnetic solid lipid nanoparticles formulation of paclitaxel (PTX
      loaded MSLNs) via emulsification-diffusion method. The physicochemical
      characterization of PTX-loaded MSLNs was performed by AFM, DLS, determination of
      entrapment efficiency (EE) and drug loading (DL), DSC, VSM, and physical
      stability. The in vitro effect of temperature and pulsed magnetic hyperthermia on
      drug release were studied. PTX-loaded MSLNs had a particle diameter around 250 nm
      with a narrow size distribution, spherical morphology, EE of 67.3 +/- 1.2% and a
      DL of 17.1 +/- 0.4 MUg/mg. A decrease of the melting point of the lipid was
      observed following the preparation of the MSLNs. A threefold increase in the in
      vitro drug release rate was seen when temperature was raised from 25 to 43 
      degrees C. The lipid coating of MPs confer a temperature-dependent drug release
      and magnetic hyperthermia was used to trigger controlled PTX release from MSLNs.

PMID- 30184782
TI  - Additively manufactured biphasic construct loaded with BMP-2 for vertical bone
      regeneration: A pilot study in rabbit.
AB  - Vertical bone augmentation of the jaws is required when the height of bone is
      insufficient at the site of dental implant placement. In this proof of concept
      study, we investigated the potential of a biphasic polycaprolactone construct
      combined with a hyaluronic acid based hydrogel loaded with recombinant human bone
      morphogenetic growth factor-2 (BMP-2) for vertical bone regeneration. The
      biphasic scaffold consisted of an outer shell manufactured by fused deposition
      modelling, mimicking native cortical bone and providing mechanical and space
      maintenance properties essential for bone formation. Within this shell, a 90%
      porous melt electrospun microfibrous mesh mimicking the architecture of
      cancellous bone was incorporated in order to facilitate hydrogel loading and
      subsequent osteogenesis and angiogenesis. The in vitro performances of the
      biphasic construct demonstrated that BMP-2 was released in a sustained manner
      over several weeks and that cell viability was maintained in the hydrogel over 21
      days. qRT-PCR demonstrated the upregulation of bone markers such as osteopontin,
      osteocalcin and collagen 1A1 at day 3 and 14 in the constructs loaded with BMP2.
      In vivo assessment of the biphasic scaffold was performed using a dose of 30 MUg
      of BMP-2 in a rabbit calvarial vertical bone augmentation model. The histology
      and micro-CT analysis of the elevated space demonstrated that the hydrogel and
      the presence of BMP-2 enabled bone formation. However, this was limited to the
      immediate vicinity of the calvarial bone. The amount of newly formed bone was
      relatively small which was likely due to poor vascularisation of the
      extraskeletal space. The utilisation of this biomimetic biphasic construct with
      excellent space maintenance properties can be of interest in dentistry although
      the in vivo model requires refinement to demonstrated appropriate efficacy.

PMID- 30184784
TI  - Optimization of reaction conditions to fabricate Ocimum sanctum synthesized
      silver nanoparticles and its application to nano-gel systems for burn wounds.
AB  - The present study deals with sequential optimization strategy based on Box
      Behnken method to optimize the process variables for efficient production of
      Ocimum sanctum synthesized silver nanoparticles using biological synthesis. Four
      substantial factors influencing the dependent variables viz size, zeta potential,
      Polydispersity index (PDI) and yield were identified as silver nitrate
      concentration, temperature, amount of plant extract and stirring speed as
      independent variables. The contribution of the studied factors in monitoring
      dependent variables was evaluated via analysis of variance. The validity of the
      model developed was verified, and the statistical analysis showed that the
      optimal operational conditions were AgNO3 concentration 5.29 mM, temperature 60 
      degrees C, agitation speed of 500 rpm and plant extract 2.24% (w/v) which primes
      to form silver nanoparticles of smallest size 83.41 nm and 0.24 with maximum zeta
      potential of -20.20mV and Yield of 18.62. In addition, the optimized AgNPs were
      characterized using DLS, TEM, FE-SEM and UV-vis analysis. The topical formulation
      was prepared by incorporation of optimized AgNPs into the carbopol gel base.
      Further, the gel was evaluated in vivo using the rat model of skin wound healing.
      The measurement of the wound areas was performed on 2nd, 4th, 6th, 8th, 10th,
      12th and 14th days and the percentage of wound closures were calculated
      accordingly. By the 14th day, silver nanoparticle gel showed 96.20% wound healing
      activity compared with that of the standard as well as control base. The
      antibacterial inhibitory efficiency of prepared nano gel was found similar to the
      commercial product against the Staphylococcus aureus, E. coli and Pseudomonas
      aeruginosa.

PMID- 30184783
TI  - Silsesquioxane polymer as a potential scaffold for laryngeal reconstruction.
AB  - Cancer, disease and trauma to the larynx and their treatment can lead to
      permanent loss of structures critical to voice, breathing and swallowing.
      Engineered partial or total laryngeal replacements would need to match the
      ambitious specifications of replicating functionality, outer biocompatibility,
      and permissiveness for an inner mucosal lining. Here we present porous polyhedral
      oligomeric silsesquioxane-poly(carbonate urea) urethane (POSS-PCUU) as a
      potential scaffold for engineering laryngeal tissue. Specifically, we employ a
      precipitation and porogen leaching technique for manufacturing the polymer. The
      polymer is chemically consistent across all sample types and produces a foam-like
      scaffold with two distinct topographies and an internal structure composed of
      nano- and micro-pores. While the highly porous internal structure of the scaffold
      contributes to the complex tensile behaviour of the polymer, the surface of the
      scaffold remains largely non-porous. The low number of pores minimise access for
      cells, although primary fibroblasts and epithelial cells do attach and
      proliferate on the polymer surface. Our data show that with a change in
      manufacturing protocol to produce porous polymer surfaces, POSS-PCUU may be a
      potential candidate for overcoming some of the limitations associated with
      laryngeal reconstruction and regeneration.

PMID- 30184786
TI  - A novel multi stimuli-responsive PEGylated hybrid gold/nanogels for co-delivery
      of doxorubicin and 6-mercaptopurine.
AB  - The clinical applications of anticancer drugs are restricted due to the
      incomplete delivery to the cancerous tissue and the numerous drug resistance
      mechanisms involved in malignant cells. In this regard, stimuli-responsive
      nanomaterials offer a promising prospect to deal with these concerns. In the
      present study, ternary responsive hybrid gold/nanogels (Au/NGs) were synthesized
      as a new nanoplatform to simultaneously carry two anticancer drugs, i.e.,
      doxorubicin (DOX) and 6-mercaptopurine (MP). For this purpose, these drugs were
      successfully loaded (the loading capacity of 23% and 11%, respectively) into the
      hybrid Au/NGs by electrostatic interaction (DOX) and AuS bonds (MP). The
      triggered drug release ability of hybrid Au/NGs was assessed by comparing the
      environments of simulated physiological and tumor tissue. The incorporation of
      disulfide bond linkers, pH sensitive, and thermosensitive polymeric segments
      endowed the NGs with an excellent property in reducing acidic and hyperthermia
      environments, which greatly facilitates drug release in tumor cells.
      Intracellular tracking of DOX@MP-Au/NGs confirmed efficient accumulation and
      cellular uptake of developed NGs and the cytotoxicity studies showed a pronounced
      tumor inhibition compared with free DOX@MP. It was concluded that the new ternary
      responsive NGs have great potential for co-delivery of DOX and MP and can be used
      in efficient cancer therapy.

PMID- 30184785
TI  - Non-enzymatic electrochemical hydrogen peroxide biosensor based on reduction
      graphene oxide-persimmon tannin-platinum nanocomposite.
AB  - Hydrogen peroxide (H2O2) is one of the most universal and essential ingredients
      in distinct biological tissues. Herein, a novel non-enzymatic sensor based on
      reduction graphene oxide-persimmon tannin-platinum nanocomposite (RGO-PT-Pt) was
      exploited for H2O2 detection. RGO-PT-Pt nanocomposite was prepared by reduction
      procedure with ascorbic acid as reducing agent and characterized by Scanning
      electron microscopy (SEM), Transmission electron microscopy (TEM), ultraviolet
      visible spectroscopy (UV-vis) and Fourier infrared spectroscopy (FT-IR). Taking
      advantage of high electro-catalytic efficiency of Pt nanoparticles, high
      electronic conductivity and large surface area of RGO, and significant adsorption
      ability of PT on metal ions and its prevention of agglomeration to promote RGO
      dispersion, RGO-PT-Pt nanocomposite revealed better catalytic ability towards
      H2O2 via a synergistic effect. Under the optimal conditions, the RGO-PT-Pt non
      enzymatic biosensor exhibited outstanding electrocatalytic activity towards H2O2
      reduction. The amperometric response demonstrated a linear relationship with H2O2
      concentration from 1.0 to100 MUM with the correlation coefficient of 0.9931. The
      limit of detection was 0.26 MUM (S/N = 3) and the response time was 3 s.
      Furthermore, the fabricated sensor exhibited a practical applicability in the
      quantification of H2O2 in human serum samples with an excellent recovery rate.
      Due to excellent performance such as fast response time, low detection limit,
      high stability and selectivity, the RGO-PT-Pt non-enzymatic biosensor has
      potential application in clinical diagnostics.

PMID- 30184788
TI  - Interpenetrating polymer network hydrogels composed of chitosan and
      photocrosslinkable gelatin with enhanced mechanical properties for tissue
      engineering.
AB  - Gelatin and chitosan (CS) are widely used natural biomaterials for tissue
      engineering scaffolds, but the poor mechanical properties of pure gelatin or CS
      hydrogels become a big obstacle that limits their use as scaffolds, especially in
      load-bearing tissues. This study provided a novel mechanism of forming
      interpenetrating network (IPN) of gelatin methacryloyl (GelMA) and CS hydrogels
      by covalent bonds and hydrophobic interactions through photocrosslinking and
      basification, respectively. By characterization of the compressive and tensile
      moduli, ultimate tensile stress and strain, it was found that semi-IPN and IPN
      structure can greatly enhance the mechanical properties of GelMA-CS hydrogels
      compared to the single network CS or GelMA. Moreover, the increase of either
      GelMA or CS concentration can strengthen the hydrogel network. Then, the
      swelling, enzymatic degradation, and morphology of GelMA-CS hydrogels were also
      systematically investigated. The excellent biocompatibility of GelMA-CS hydrogels
      was demonstrated by large spreading area of bone mesenchymal stem cells on
      hydrogel surfaces when CS concentration was <2% (w/v). According to this study,
      the multiple requirements of properties can be fulfilled by carefully selecting
      the GelMA and CS compositions for IPN hydrogels.

PMID- 30184787
TI  - AIE-active self-assemblies from a catalyst-free thiol-yne click reaction and
      their utilization for biological imaging.
AB  - Aggregation-induced emission (AIE) should be the most interest fluorescent
      phenomenon over the past few decades. The luminescence polymeric nanoparticles
      (LPNs) with AIE characteristic have attracted great research attention for
      biological imaging and many other biomedical applications owing to their good
      biocompatibility and negative toxicity. However, the preparation of LPNs with
      desirable optical properties using traditional organic dyes still remains a great
      challenge for the aggregation-caused quenching (ACQ) effect and aggregation of
      hydrophobic dyes in the core of LPNs. In this work, we reported a novel and
      simple method for fabrication of biodegradable AIE-active LPNs via the
      combination of condensation and click reactions. For preparation of these AIE
      active LPNs, the thiol groups-containing hydrophilic copolymers (PEG-MA) were
      first synthesized through the condensation reaction between polyethylene glycol
      and mercaptosuccinic acid. The PEG-MA copolymers were further reacted with AIE
      dye PhE-OE through a catalyst-free thiol-yne click reaction. These obtained PEG
      MA-PhE LPNs were fully characterized by a number of characterization techniques.
      All the results confirmed that PEG-MA-PhE LPNs possess excellent compatibility,
      intense red luminescence, great photostability and high water dispersibility.
      These features make PEG-MA-PhE LPNs promising candidates for various biomedical
      applications.

PMID- 30184789
TI  - Evaluation of anti-biofilm and cytotoxic effect of a gel formulation with
      Pluronic F-127 and silver nanoparticles as a potential treatment for skin wounds.
AB  - The skin wounds cause serious burden to healthcare systems. The lack of sterility
      of the innate barrier function of the skin facilitates the development of
      microbial communities within the wound environment especially in biofilm form.
      Since biofilm is difficult to eradicate, new treatments have been established,
      such as silver nanoparticles (AgNPs), which antimicrobial and anti-biofilm
      properties have been studied, nevertheless, their toxic effects are known too.
      Different concentrations of AgNPs stabilized with a biocompatible and thermo
      reversible vehicle as hydrogel Pluronic F-127 were synthesized, those
      formulations presented interesting thermo-reversibility which could be used to
      apply on wounds. The formulations (Gel 62.5, 125, and 250 ppm of AgNPs) proposed
      in this study showed in vitro a total inhibition of clinical strains
      (Staphylococcus aureus and Pseudomonas aeruginosa) in planktonic form, as well
      as, anti-biofilm activity was archived with the formulation of Gel 250 ppm, a
      total inhibition of biofilm formation with mixed culture was registered in the
      first 30 min of biofilm growth; even more, the viability of human fibroblasts
      with all gels formulations was >95%, in contrast to silver sulfadiazine cream 1%
      which showed the highest cytotoxic effect. PF-127 gel with AgNPs could be a
      prophylactic treatment for skin wounds, because its activity in critical steps on
      biofilm formation.

PMID- 30184790
TI  - Doxorubicin delivery via magnetic nanomicelles comprising from reduction
      responsive poly(ethylene glycol)-b-poly(epsilon-caprolactone) (PEG-SS-PCL) and
      loaded with superparamagnetic iron oxide (SPIO) nanoparticles: Preparation,
      characterization and simulation.
AB  - Reduction-responsive biodegradable micelles were prepared by linking of
      poly(ethylene glycol) and poly(epsilon-caprolactone) with disulfide bond (PEG-SS
      PCL) for co-delivery of superparamagnetic iron oxide (SPIO) nanoparticles (NPs)
      and an anticancer agent, doxorubicin (DOX). This amphiphilic diblock copolymer
      shows redox-responsive properties, which is arising from disulfide bonds
      throughout the main chain. The ability of these copolymers for self-assembly with
      oleic acid modified SPIONs can help to organize nanomicelles in aqueous solution.
      Doxorubicin (DOX) was loaded in the magnetic nanomicelles with a loading of 32%.
      Coarse-Grained Molecular Dynamics (CG-MD) simulation approach was exploited to
      reassure the construction of self-assembled PEG-PCL micelles in presence of oleic
      acid and water solvent while the hydrophobic and hydrophilic ratios of each block
      copolymer were equally chosen and each oleic acid was connected to Fe3O4
      nanoparticles. Our results confirmed the stability, cytocompatibility, magnetic
      and redox-responsive properties for these self-assembled nanomicelles and
      revealed that the DOX-SPION-loaded reduction-sensitive nanomicelles could be used
      in drug targeting to the cancer cells.

PMID- 30184791
TI  - Synthesis and characterization of metals-substituted cobalt ferrite [Mx Co(1-x)
      Fe2O4; (M = Zn, Cu and Mn; x = 0 and 0.5)] nanoparticles as antimicrobial agents
      and sensors for Anagrelide determination in biological samples.
AB  - Nanocrystalline spinel ferrite nanoparticles [MxCo(1-x)Fe2O4;(M = Zn,Cu,Mn;x = 0
      and 0.5)] like: Cobalt ferrite (CFO), Zinc Cobalt ferrite (ZCFO), Copper Cobalt
      ferrite (CCFO), and Manganese Cobalt ferrite (MCFO) modified carbon paste
      electrodes (CPE) were synthesized via sol-gel technique utilizing citric acid and
      ethylene glycol as a polymerization agent. The synthesized ferrite NPs were used
      as bi-functional smart biosensor, not only used to determine the drug Anagrelide
      HCl (ANDH) in urine and serum samples, but also possesses antimicrobial potential
      against some pathogenic microbes, founded in the biological samples. The
      synthesized ferrite NPs were confirmed by XRD, FTIR spectroscopy, SEM, EDX, and
      elemental mapping images. Antimicrobial activities of ferrite NPs against
      selected urinary tract infected microbes were investigated. From XRD data and
      FTIR spectroscopy it is found that the average crystallite size is lies in the
      range 12.86 to 33.92 +/- 1.5 nm, also the bond lengths RA and RB increase from
      1.8986 to 1.9145 A and from 2.0434 to 2.0606 A respectively and Debye temperature
      thetaD lies in the range of 681.52-708.87 K. Our study describes the improvement
      of a screen-printed sensor, modified with ferrite NPs materials for rapid,
      sensitive and cost-effective quantification of ANDH present in the real samples
      such as blood serum samples, urine and in the pharmaceutical formulations. The
      results obtained postulate a linear regression between the ANDH charge density of
      peak current and its concentration in the range from (0.64-8.18 MUg/ml) with DL
      0.31 MUg/ml and QL 0.94 MUg/ml. Antimicrobial results indicated that ZCFO NPs
      were a novel antibacterial agent against Klebsiella pneumoniae (28.0 mm ZOI), and
      multidrug-resistant bacteria Enterococcus faecalis (27.0 mm ZOI). Additionally,
      ZCFO NPs were active against Candida albicans (18.0 mm ZOI) seems to be a smart
      antifungal agent. Therefore, ZCFO NPs can be used as applicant resources for
      industrial, medical, and biological applications.

PMID- 30184792
TI  - An irreversible temperature indicator fabricated by citrate induced face-to-face
      assembly of silver triangular nanoplates.
AB  - Assembly of anisotropic nanoparticles which need well controlling of assembly
      direction and spatial arrangement is more interesting than one-dimensional
      nanoparticles assemblies. As confirmed by observing of transmission electron
      microscopy images and analysis of plasmon resonance spectrum transformations, we
      found that silver triangular nanoplates (TNPs) without further modification could
      be face-to-face assembled by citrate. The face-to-face assembly of silver TNPs
      could be disassembled quickly by heating at a wide temperature range from 30 to
      80  degrees C. In this process, an obvious localized surface plasmon resonance
      (LSPR) peak shift and a color change of solution from pink to purple could be
      observed. Moreover, the disassembled silver TNPs suspension is very stable that
      no significant peak shift of silver TNPs spectrum was observed in 8 h after
      removing of silver TNPs from a hearing area. Therefore, we fabricated an
      irreversible temperature indicator by measuring the relationship between the
      shift of LSPR peak and heating temperature, and by watching the color change of
      the solution in a certain environment. The irreversible temperature indicator has
      potential to develop a temperature label for revealing temperature history of a
      thermosensitive product which cannot expose to excessive temperature.

PMID- 30184793
TI  - ZnO-SiO2 nanohybrid decorated sustainable geopolymer retaining anti
      biodeterioration activity with improved durability.
AB  - Geopolymer, consists of industrial by-product fly ash, and alkaline activator,
      possesses similar strength along with durability like conventional cement
      composite, is an alternative construction substantial of Portland cement in
      current scenario. Corrosion of the concrete materials resulted mainly from the
      chemical degradation. Besides chemical degradation, biogenic-deterioration is
      also another alarming issue especially in the sewer systems, bridge piers,
      several pipelines and offshore platforms and the need to act on it is long
      standing. In this study, application of zinc oxide-silica nanohybrid based
      sustainable geopolymer (GMZnO-Si) has been investigated for the development of a
      sustainable, anti-biodeteriorate cementitious material having significant
      mechanical strength and durability. Initially, zinc oxide nano-rods (ZnO NRs)
      have been synthesized and spherical silica nanoparticles were decorated on the
      surface of ZnO NRs. The ZnO-SiO2 composite was characterized by various
      techniques (FTIR, XRD, FESEM, EDS, TEM, and XPS). Ambient temperature cured GMZnO
      Si mortar was further explored in terms of mechanical strength, durability,
      mechanistic anti-microbial (E. coli, S. aureus, A. niger) influences. Mechanical
      properties of GMZnO-Si are found significantly higher than that of control
      samples. MIC, MBC, and MFC results demonstrate enhanced anti-microbial efficacy
      of GMZnO-Si. Inner permeability assay, reactive oxygen species generation and
      microscopic images of cell wall rupture and DNA damage studies supported the
      detailed understanding of anti-microbial activities. These experimental findings
      suggest that incorporation of ZnO-SiO2 hybrid in geopolymer will pave the way for
      biodeterioration resistant concrete with enhanced mechanical and structural
      behaviour.

PMID- 30184794
TI  - Co-delivery of curcumin and serratiopeptidase in HeLa and MCF-7 cells through
      nanoparticles show improved anti-cancer activity.
AB  - Curcumin was employed to prepare anticancer nanoparticles (size 175 +/- 15 nm)
      using anti-inflammatory enzyme serratiopeptidase by desolvation method. Here
      serratiopeptidase acted as a carrier as well as bioactive molecule in the
      nanoformulations. The Cur-SPD NPs (curcumin loaded serratiopeptidase
      nanoparticles) were characterized using DLS, FESEM and FTIR. The in vitro release
      behavior depicted biphasic pattern at 37  degrees C (pH 7.4) and release of 95%
      of both molecules occurred in 24 h. Serratiopeptidase not only provided stability
      to curcumin but also increased its effectiveness against cancer cells. These
      nanoparticles had anti-cancer activity in MCF-7 and HeLa cell lines as shown by
      cytotoxicity assay, DAPI nuclear staining, ROS production and DNA damage. The
      immunomodulatory tests showed that Cur-SPD NPs reduce level of IL-6 but increase
      TNFalpha level in THP1 cell lines. Structural similarity of serratiopeptidase to
      matrix metallo proteases (MMPs), particularly MMP8, have been found (based on low
      RMSD values) to induce TNFalpha production and play tumour suppressive role in
      certain cancers. Thus anti-cancer properties of Cur-SPD NPs may be attributed to
      synergistic effect of curcumin and serratiopeptidase. Thus results in present
      investigation provide an insight on role of serratiopeptidase in development of
      co-delivery of multifunctional nanoparticles with anti-cancer properties
      introduction.

PMID- 30184795
TI  - New core-shell hydroxyapatite/Gum-Acacia nanocomposites for drug delivery and
      tissue engineering applications.
AB  - Core-shell hydroxyapatite (HAP) - gum acacia (GA) nanocomposite, in which the HAP
      acts as a core while the GA serves as a shell, was synthesized by precipitation
      techniqueusing Ca(NO3)2.4H2O and NH4H2PO4as precursors for Ca and P,
      respectively. The crystallite size and morphology of the synthesized core-shell
      HAP-GA nanocomposite was evaluated by X-ray diffraction measurement and
      transmission electron microscopy. The crystallite size of GA-HAP nanocomposite is
      markedly decreased from 89 nm to 63 nm when the concentration of GA in the
      reaction mixture is increased from 0 to 10%. Transmission electron micrographs
      confirm encapsulation of GA over the HAP particles, leading to the formation of
      GA shell-HAP core assembly, which is quite evident for 10% GA-HAP composites. The
      nature of functional groups present in HAP was identified using FT-IR and Raman
      spectroscopies while its chemical composition was analyzed by energy dispersive X
      ray analysis. The Ca/P ratio of the synthesized HAP's was found to be 1.67. The
      elemental composition of the HAP samples was evaluated by X-ray photoelectron
      spectroscopy. The peaks at binding energies 286.5 and 289.3 eV of C 1S and the
      peaks at 530.6 eV and 532.1 eV of the O 1S spectra further substantiate
      encapsulation of GA over the HAP particles, resulting in the formation of GA-HAP
      nanocomposite. Pellet samples of HAP were immersed in simulated body fluid to
      ascertain their bioactivity using scanning electron micrographs. The drug,
      naringenin, was loaded within the core of HAP by pellet pressing method. The drug
      loaded core-shell HAP composites were subjected to microbial studies, hemolytic
      studies and MTT assay to assess their biocompatibility.

PMID- 30184796
TI  - Critical assessment of polymeric nanostructures used as colorimetric ions probes.
AB  - In this study the effect of nature of nanostructural materials used as
      colorimetric optical probes on the analytical performance of the resulting
      sensors is compared. Different effects related to the nanoprobe materials - probe
      structure and properties: surface charge and stability, but also effects related
      to the analyte - receptor interactions - complex formation kinetics and transport
      of ions from the sample to the probe were taken into account. Presence of charge
      on the nanostructural colorimetric sensor effectively hinders ions exchange
      between the probe and the sample, leading to a linear dependence of absorbance on
      logarithm of analyte concentration changes. Interestingly, both anionic and
      cationic micelles are offering linear dependence on logarithm of concentration,
      covering 2 logarithmic units. Nanostructures, e.g. prepared from amphiphilic
      polymer Pluronic F127, lead to absorbance dependence on concentration observed in
      rather narrow concentration range. In this respect crosslinked poly(maleic
      anhydride-alt-1-octadecene) nanostructures of pH tunable surface charge, due to
      the presence of carboxyl and amine group on the surface, seem an attractive
      alternative, offering also the lowest detection limits among tested systems. This
      system is stable even in the presence of high concentration of background
      electrolyte in the sample and offers the lowest detection limit, what makes it
      useful as e.g. indicator for titration. Generally from the results obtained it
      follows that inert complexes, hindering ion transport to the probe, can be used
      to expose a linear dependence of the optical signal on logarithm of
      concentration, whereas for labile complexes formed sigmoidal type dependences of
      higher sensitivity over limited concentration range are obtained.

PMID- 30184797
TI  - Succinyl-beta-cyclodextrin: Influence of the substitution degree on albendazole
      inclusion complexes probed by NMR.
AB  - Succinyl-beta-CD derivatives were obtained by green synthesis with degrees of
      substitution (DS) 1.3 and 2.9. The spray-drying technique was used to obtain
      albendazole (ABZ):succinyl-beta-CD inclusion complexes. Phase solubility diagrams
      indicated that both succinyl-beta-CD derivatives formed 1:1 molar ratio ABZ
      complexes, but the complex with DS 2.9 has a lower formation constant. The
      presence of stable inclusion complexes in aqueous solution was confirmed by NMR.
      For both complexes the aromatic moiety is encapsulated into the host cavity. In
      the solid-state, 13C and 15N NMR spectral differences between ABZ and ABZ
      included in spray-dried systems showed that strong structural changes occurred in
      the systems. At least two different ABZ amorphous species were identified based
      on DS. ABZ species were stable over more than six months based on spectral data.
      Finally, the influence of DS in the number and type of the inclusion complexes
      was elucidated.

PMID- 30184798
TI  - Sequential or multiplex electrochemical detection of miRs based on the p19
      function relative to three sandwiches of different structural hybrids on the
      liposomal sensor.
AB  - In this work, we designed a liposomal electrochemical sensor with DOTAP-DOPE
      liposome, chimeric probes, p19 as a caliper molecule, and the competitor
      structural hybrid (just RNA) for detection of three micro-RNAs in one SPCE/GNP
      electrode. The sensor is stabled when the cationic spherical DOTAP-DOPE liposomes
      sandwich with hybrids of the different sandwiched of probes (T-M-linear, Stem)
      and 21-124a-221miRs. With the addition of P19, in the presence of a sandwiched
      competitor (T-linear/21miR), the system is stable (ON) and is shut off in the
      presence of structural sandwiched hydrides of M-linear+124a/Stem+221 miR due to
      the lack of adequate access to segments of RNA-miRs of chimeric probes. For the
      first time in this study, three probes were sandwiched on the separate liposome
      for sequential identification of 21-124a-221 or multiplex detection of miRs (221
      or 124a with 21) with high specificity and sensitivity (as low as 0.1 fM).
      Electrochemical impedance (EIS) were performed for sensing three miRs in PBS
      containing 1 mM [Fe(CN)6]-3/-4 which DOTAP-DOPE liposome acted as an enhancing
      intermediate layer in the electrochemical reactions. Transmission Electron
      Microscopy (TEM)), Atomic Force Microscopy (AFM), Dynamic Light Scattering (DLS)
      and Ultraviolet-Visible (UV) spectroscopic techniques are used to understand the
      interactions between the DOPE-DOTAP, AuNP, different probes, miRs and p19.

PMID- 30184799
TI  - Mesoporous and hollow hydroxyapatite nanostructured particles as a drug delivery
      vehicle for the local release of ibuprofen.
AB  - The high risk of infection caused by implantation of orthopedic bio-metals is
      still a daunting challenge for surgeons as it can lead to implant failure. One
      approach to overcome this issue is the local release of antibacterial drug
      through coating on the surface of a metallic implant. One ideal carrier for this
      purpose is hydroxyapatite (HA) particles which are bioactive, biodegradable,
      biocompatible and have the potential to bond to bone. In the current study,
      highly crystalline mesoporous HA nanostructure particles were successfully
      synthesized in a low-temperature solvent process with the aid of an inorganic
      CaCO3 template and then fully characterized. The specific surface area and the
      average size of the cavities of the nanostructured mesoporous HA particles were
      85 m2/g and 20 nm, respectively. The feasibility of the prepared HA mesoporous
      nanostructures for drug delivery, using ibuprofen as a model drug, was also
      investigated. The as-prepared HA mesoporous nanostructures showed a high drug
      loading capacity, as well as sustained drug release in a phosphate buffered
      saline (PBS) at a pH of 7.4. Overall, results show that HA mesoporous
      nanostructures gave great potential in bone regeneration and local delivery of
      either drugs or biomolecules.

PMID- 30184800
TI  - Quantum dots attached to graphene oxide for sensitive detection of ascorbic acid
      in aqueous solutions.
AB  - Water-soluble fluorescent carboxyl-functionalized CdSe-ZnS quantum dots (QDs)
      were immobilized on graphene oxide (GO) and used for sensitive detection of
      ascorbic acid in aqueous solutions. QDs were attached to the surface of graphene
      oxide using the EDC/NHS-sulfo coupling reaction. Ascorbic acid is known as an
      antioxidant. It plays a crucial role in health maintenance, bio synthetic
      pathways such as formation of collagen and regulates immune system. The
      photoluminescence (PL) intensity of as-prepared GO-QD hybrids in water was
      quenched by ascorbic acid at ambient temperature. Based on this photoluminescence
      quenching phenomenon, a simple, rapid, and sensitive procedure is developed. In
      this study we are successful in detecting ascorbic acid due to its biological
      significance and the limit of detection is 568 pM.

PMID- 30184801
TI  - Construction and characterization of an antibacterial/anticoagulant dual
      functional surface based on poly l-lactic acid electrospun fibrous mats.
AB  - In this study, a poly l-lactic acid (PLLA) fibrous mat was prepared by
      electrospinning, followed by surface modification with polydopamine (PDA), based
      on its strong adhesion performance and self-polymerization of dopamine. The PDA
      coating on the fibrous mat surface provided a reaction platform for heparin via a
      Michael-type addition reaction and a reductive surface for Ag+ in situ formation
      of silver nanoparticles (AgNPs) in AgNO3 solution. The structure and chemical
      composition of the fibrous mats were determined by scanning electronic microscopy
      (SEM), X-ray photoelectron spectroscopy (XPS), and attenuated total reflectance
      Fourier transform infrared (ATR-FTIR) spectroscopy. All the results confirmed the
      successful immobilization of heparin and AgNPs on the PLLA fibrous mats.
      Thermogravimetric analysis (TGA) and energy dispersive X-ray spectrum (EDS)
      analysis were used to determine the content of AgNPs and their distribution on
      the fibrous mat surface. Water contact angle measurements showed the hydrophilic
      improvement after modification. The antibacterial investigation indicated that
      the fibrous mats could inhibit the growth of both Escherichia coli (E. coli) and
      Staphylococcus aureus (S. aureus). Protein adsorption, the hemolysis test, the
      coagulation test, complement activation, and platelet activation were used to
      confirm the compatibility with blood and the anticoagulation property of the
      fibrous mats. Finally, cell proliferation and live/dead assays, conducted with
      cultured fibroblasts on the fibrous mats, showed that the modified fibrous mat
      surface had good cell compatibility. This antibacterial/anticoagulant dual
      functional surface, based on poly l-lactic acid electrospun fibrous mats, would
      have potential application in blood contacting materials.

PMID- 30184802
TI  - Photodynamic therapy evaluation of methoxypolyethyleneglycol-thiol-SPIONs-gold
      meso-tetrakis(4-hydroxyphenyl)porphyrin conjugate against breast cancer cells.
AB  - Magnetic field enhanced photodynamic therapy is an effective non-invasive
      technique for the eradication of cancer diseases. In this report, magnetic field
      enhancement of the photodynamic therapy (PDT) efficacy of a novel
      methoxypolyethyleneglycol-thiol-SPIONs-gold-meso-tetrakis(4
      hydroxyphenyl)porphyrin conjugate (nano-drug) against MCF-7 breast cancer cells
      was evaluated. The nano-drug exhibited excellent blue and red emissions under
      suitable ultraviolet (380 nm) and visible (430 nm) excitations and was well taken
      up by the cells without any significant dark cytotoxicity after 24 h post
      incubation. However, after exposure of cells to light for about 15 min, high rate
      of cell death was observed in a dose-dependent manner. In addition, the cells
      that were exposed to external magnetic field displayed higher phototoxicity than
      the non-exposed cells. Altogether, these results suggest that the nano-porphyrin
      drug system can function as a new promising magnetic-field targeting agent for
      theranostic photodynamic eradication of cancer diseases.

PMID- 30184803
TI  - Reduction-sensitive polypeptide nanogel conjugated BODIPY-Br for NIR imaging
      guided chem/photodynamic therapy at low light and drug dose.
AB  - A heavy atoms modified reaction-active photosensitizer NHS-BODIPY-Br possessing
      efficient near infrared (NIR) fluorescence emission and singlet oxygen generation
      properties has been synthesized, which can be used for synchronous NIR imaging
      and photodynamic therapy (PDT). A reduction-sensitive PEGylated polypeptide
      nanogel was prepared by ring-opening polymerization (ROP) of l-cystine-N-carboxy
      anhydride. Poly (ethylene glycol) methyl ether was used as initiator and
      hydrophilic segment, the as-prepared nanogel was conjugated with the NHS-BODIPY
      Br molecule by chemical linkage, and it can be directly used as a
      macrophotosentizer for NIR imaging-guided PDT. In addition, the nanogel also
      showed good encapsulating ability for doxorubicin (DOX). In the presence of
      glutathione (10 mM), the obtained NIR nanogel showed obvious reduction-induced
      drug release behavior. In vitro tests on internalization of the NIR nanogel by
      HepG2 cells indicated its efficiency in detecting cancer cells. Meanwhile, MTT
      assays performed on HepG2 cells confirmed that the cancer cells growth could be
      obviously suppressed (almost all cells) when exposed to an extremely low energy
      light (25 mW/cm2, 10-15 J/cm2) and low dose of DOX (3-5 MUg/ml), indicates an
      efficient NIR image-guided chem/photodynamic therapy.

PMID- 30184804
TI  - 3D porous collagen/functionalized multiwalled carbon
      nanotube/chitosan/hydroxyapatite composite scaffolds for bone tissue engineering.
AB  - In this study, we describe new collagen/functionalized multiwalled carbon
      nanotube/chitosan/hydroxyapatite (Col/f-MWCNT/CS/HA) composite scaffolds which
      were fabricated by freezing (-40  degrees C at 0.9  degrees C/min) and
      lyophilization (48 h, 0  degrees C and 200 mtorr). The compressive stresses (from
      523 to 1112 kPa), swelling (from 513.9 +/- 27 to 481.05 +/- 25%), porosity (from
      98 +/- 0.15 to 95.7 +/- 0.1%), contact angle (from 87.8 to 76.7 degrees )
      properties examined before and after biomineralization for comparison 3D porous
      Col, CS, Col/f-MWCNT and Col/f-MWCNT/CS scaffolds. Biomineralization was
      performed by biomimetic method in concentrated SBF (10 * SBF, at 37  degrees C
      and 6.5 pH). XRD, SEM, EDS, FTIR, TGA, Optical microscopy and BET results showed
      that compared to Col, CS and Col/f-MWCNT scaffolds, Col/f-MWCNT/CS scaffolds had
      higher in vitro bioactivity, large surface area (11.746 m2/g) and a good pore
      volume (0.026 cc/g), interconnected porous microstructure (with 20-350 MUm pore
      size) and incorporates the advantageous properties of both Col, f-MWCNT, CS and
      HA. Finally, the methyl thiazolyl tetrazolium (MTT) assay was performed to
      evaluate scaffolds cytotoxicity which showed that Col/f-MWCNT/CS scaffolds have
      the best biocompatibility.

PMID- 30184805
TI  - Physical nanocomposite hydrogels filled with low concentrations of TiO2
      nanoparticles: Swelling, networks parameters and cell retention studies.
AB  - Physical nanocomposite hydrogels composed of poly(2-hydroxyethylmethacrylate) and
      titanium oxide nanoparticles at low concentrations (<1.0 wt%) were synthesized.
      The effect of the nanoparticle content on the water swelling and mechanical
      properties of the hydrogels was investigated. Additionally, to study the
      influence of the polymer-nanoparticle interactions, a second type of
      nanocomposite was synthesized using surface functionalized nanoparticles with 3
      methacryloxypropyltrimethoxysilane as the filler. The pristine nanoparticles
      increased the swelling capacity, especially at short time scales, and greater
      solvent diffusion coefficients and initial swelling rates were achieved. In
      contrast, the nanocomposite filled with functionalized nanoparticles exhibited a
      diminished swelling capacity, a constant diffusion coefficient and a significant
      decrease in the initial swelling rate. The mechanical properties were studied by
      dynamic mechanical analyses using stress-relaxation tests. Two Maxwell models in
      parallel agreed well with the curves of the relaxation modulus as a function of
      time and indicated that at short relaxation times, the nanoparticles did not
      cause an effect, but that at longer times, the nanoparticles decreased the
      relaxation time. Finally, hydrogel network parameters determined by swelling
      measurements and mechanical experiments indicated that the hydrogel with well
      distributed nanoparticles decreases the molar mass between crosslink point and
      the mesh size, while poorly distributed nanoparticles lead to larger mesh size.
      Our functional studies show that the addition of titanium oxide nanoparticles
      improves the ability of nanocomposite hydrogels to retain aggregates of skeletal
      muscle cells, revealing their potential use as suitable scaffolds for tissue
      repair strategies.

PMID- 30184806
TI  - A highly-sensitive VB2 electrochemical sensor based on one-step co
      electrodeposited molecularly imprinted WS2-PEDOT film supported on graphene oxide
      SWCNTs nanocomposite.
AB  - A highly-sensitive electrochemical sensor based on single walled carbon nanotubes
      (SWCNTs) nanocomposite electro-catalyst supported molecularly imprinted poly(3,4
      ethylenedioxythiophene) (PEDOT) film modified with two-dimensional layered
      tungsten sulfide (WS2) nanosheet for the detection of vitamin B2 (VB2) was
      successfully developed. Molecularly imprinted WS2-PEDOT film was prepared by the
      electrochemical co-polymerization of functional monomer 3,4
      ethylenedioxythiophene in the presence of template molecule VB2 and WS2
      nanosheet. SWCNTs nanocomposite modified electrode was obtained by drop-coating
      SWCNTs dispersion containing graphene oxide (GO) onto GCE surface. WS2 was used
      for improving the denseness and smoothness in the morphology and structure of
      PEDOT. GO was employed for enhancing the electro-catalytic capacity of SWCNTs and
      the interaction with template molecule via functional groups. The imprinted
      sensor was characterized, and its performance and parameters were investigated
      and optimized using linear sweep voltammetry. Under optimized conditions, the
      prepared imprinted sensor displayed a good linear response to VB2 in wide
      concentration ranges from 0.002 to 0.9 MUM with a low detection limit of 0.7 nM,
      and successfully applied to electrochemically detect VB2 in drug samples with
      good reproducibility, repeatability and storage stability. The new design for the
      facile fabrication of mimic electrode will open up a new horizon in the
      development of highly-sensitive biomimic/imprinted sensors.

PMID- 30184807
TI  - Mechanical and biological performance of printed
      alginate/methylcellulose/halloysite nanotube/polyvinylidene fluoride bio
      scaffolds.
AB  - Use of artificial cartilage due to its poor regenerative characteristics is a
      challenging issue in the field of tissue engineering. In this regard, three
      dimensional printing (3D) technique because of its perfect structural control is
      one of the best methods for producing biological scaffolds. Proper biomaterials
      for cartilage repairs with good mechanical and biological properties and the high
      ability for 3D printing are limited. In this paper, a novel biomaterial
      consisting of Alginate (AL), Methylcellulose (MC), Halloysite Nanotube (HNT), and
      Polyvinylidene Fluoride (PVDF) was printed and characterized for cartilage
      scaffold applications. Calcium chloride (CaCl2) was used as a crosslinker for
      biomaterial after printing. Scanning Electron Microscopy (SEM), Energy-Dispersive
      X-Ray Spectroscopy (EDX), X-Ray Diffraction (XRD), Fourier-Transform Infrared
      Spectroscopy (FT-IR), Differential Scanning Calorimetry (DSC), tensile and
      compressive tests, chondrocytes seeding, cells staining, and MTT assay were
      carried out in the present work. The results show that in constant concentrations
      of AL, MC, and PVDF (40 mg/ml AL, 30 mg/ml MC, and 1% PVDF) when concentration of
      HNT increased from 20 mg/ml (S2) to 40 mg/ml (S14) tensile strength increased
      from 164 up to 381 kPa and compressive stress increased from 426 up to 648 kPa.
      According to spectroscopy and calorimetry results, Biomaterial shows an amorphous
      structure with good miscibility and a high percentage of water in its structure.
      PVDF reduces mechanical properties by 7% while increases cell viability by 8.75%.
      Histological studies and MTT assay results showed a high improvement in the
      percentage of living cells at the first 4 days of cell cultivation.

PMID- 30184808
TI  - Self-assembled block copolymer [(BenzA)-b-(PCL)] micelles to orient randomly
      distributed AuNPs into hollow core-shell morphology and its role as payload for
      nanomedicines.
AB  - Synthesis and characterization of the di-block copolymer (di-BCP) of [(BenzA)-b
      (PCL)] between benzyl alcohol (BenzA) and poly-E-caprolactone (PCL) follow the
      development of micelles has been carried out. These developed [(BenzA)-b-(PCL)]
      based micelles are acting as an adjunct to assemble and arrange gold
      nanoparticles (AuNPs) in particular shape. Polymeric micelle driving randomly
      arranged AuNPs to form hollow core-shell (hCS) type morphology in a stringent
      assembler manner. The synthesis of [(BenzA)-b-(PCL)] has been performed through
      addition polymerization methods without using any surfactants and precursors. The
      average size of AuNPs is ~18 nm (in diameter). Interestingly, di-BCP based
      micelles formulation and their role in arranging AuNPs into hCS is a novel and
      unique approach to develop carrier capsules in biomedical field as well as drug
      delivery systems (DDSs). The average core size is ~44 nm with shell size of ~26
      nm. However, [(BenzA)-b-(PCL)-(AuNPs)] based hCS capsules were used as payload
      for anticancer drug doxorubicin hydrochloride (DOX) for controlled release.
      Moreover, these [(BenzA)-b-(PCL)-(AuNPs)] based hCS are pH sensitive. It
      disintegrates at acidic pH (~5.3) and releases DOX molecules in a sustained
      manner. Furthermore, these [(BenzA)-b-(PCL)-(AuNPs)] based hCS are appended and
      evidenced as best carrier capsules for nano-medicines with enhanced loading
      efficacy (~74%) and dosage based prolonged release kinetics.

PMID- 30184809
TI  - Biodegradable bead-on-spring nanofibers releasing beta-carotene for bone tissue
      engineering.
AB  - Bead-on-string mats based on poly(lactide-co-glycolide) (PLGA) releasing beta
      carotene (betaC) as a natural osteogen were fabricated and used for bone tissue
      engineering. Mesenchymal stem cells (MSCs) seeded on the scaffolds successfully
      differentiated to osteoblasts without using any a differential medium. The mats
      showed a small burst of beta-carotene (24-27%) during the first day and a
      sustained slow release up to 21 days. The MTT and SEM results indicated good
      attachment and proliferation of MSCs on the scaffolds. Calcination of scaffolds
      and expression of RUNX2, SOX9, and osteonectin genes approved the differentiation
      of seeded MSCs to osteoblasts without using any external osteogenic differential
      agent. The scaffold loaded with 4% beta-carotene not only induced the early phase
      of osteogenesis but also advanced the differentiation to the osteoblast
      maturation phase. Thus, these bead-on-string scaffolds can be used as a substrate
      for direct bone tissue engineering.

PMID- 30184810
TI  - Molecular insights to alkaline based bio-fabrication of silver nanoparticles for
      inverse cytotoxicity and enhanced antibacterial activity.
AB  - High demand for silver nanoparticles due to their extensive applications in
      different field has raised need of eco-friendly green synthesis with determined
      biomedical effects. This study proposes a novel rapid controlled alkaline based
      green synthesis of antibacterial silver nanoparticles from Calotropis gigantea
      for reduced cytotoxic effects. Silver nanoparticles termed as FAg, FAg1N, and
      FAg5N were synthesized with the help of floral extract of Calotropis gigantea as
      reducing and capping agent in presence of UV light and NaOH for catalysis and
      were characterized for their physiochemical properties by FESEM, DLS, UV-Visible
      spectrophotometry and FTIR. Facile synthesized Silver nanoparticles FAg1N and
      FAg5N showed enhanced antibacterial effects than FAg with increased NaOH
      concentration. Cytotoxic effect was found to be reduced at optimized alkaline
      conditioned FAg1N than FAg and FAg5N. Molecular dynamics study depicted the
      significant role of configurational change in "Calotropin" at variable alkalinity
      for controlling the size and physiological properties of synthesized AgNPs. The
      mechanism of cytotoxicity was revealed as consequences of variability in the
      interaction of Sod1 and P53 proteins with AgNPs surface for oxidative stress
      induction and programmed cell death.

PMID- 30184811
TI  - Hemocompatibility of plasma electrolytic oxidation (PEO) coated Mg-RE and Mg-Zn
      Ca alloys for vascular scaffold applications.
AB  - Percutaneous transluminal coronary angioplasty and subsequent vascular scaffold
      implantation remains the prevalent invasive treatment of coronary heart disease.
      In-stent restenosis remained a problem with bare metal stents, until drug-eluting
      stents were introduced. The inhibition of the healing process by the antimitotic
      drug coating and the permanent metallic remnant can promote sub-acute and delayed
      stent thrombosis. Thus, the development of biodegradable stents emerged as a
      subject of research. Magnesium-based bioabsorbable devices can provide sufficient
      radial force in the acute phase of vessel-treatment and degrade thoroughly in
      aqueous environment, making them potential new candidates for vascular scaffold
      applications. Magnesium alloys tend to degrade very quickly due to their high
      electrochemical corrosion potential. Plasma Electrolytic Oxidation modification
      of magnesium alloys improves interface and degradadation properties and may
      therefore enhance the performance and suitability for vascular scaffold
      applications of these materials. Assuring the hemocompatibility and foremost
      assessing the thrombogenicity of new biomaterials prior to their use is essential
      in order to avoid adverse effects. The goal was to assess thrombocyte adhesion on
      coated Mg-RE and Mg-Zn-Ca alloys. Static experiments with human blood were
      carried out on the plasma-electrolytically treated or corresponding untreated Mg
      alloy in order to assess quantity and quality of thrombocyte adhesion via
      standardized SEM imaging. In a second step, a parallel plate flow chamber was
      designed in order to examine thrombocyte adhesion under dynamic flow conditions.
      During flow chamber experiments the test-materials were exposed to human
      thrombocyte concentrate and the number of adherent thrombocytes was assessed. The
      flow chamber was additionally perfused with human blood and thrombocyte adhesion
      was semiquantitatively and qualitatively assessed via SEM imaging and subsequent
      scoring. In conclusion, a new parallel plate flow chamber design simulating blood
      circulation was successfully established, enabling the further assessment of
      platelet adhesion on bioabsorbable materials under dynamic flow conditions.
      Static and dynamic experiments showed, that plasma-electrolytically treated
      specimens showed low thrombocyte adhesion on both alloys, proposing their
      potential use in vascular scaffolds. The uncoated magnesium alloys showed rapid
      degradation along with gas formation due to the chemically active surface and
      therefore give concern regarding their safety and suitability for vascular
      applications.

PMID- 30184812
TI  - Sodium caseinate-magnesium aluminum silicate nanocomposite films for modified
      release tablets.
AB  - The aim of this study was to investigate the effect of clay, magnesium aluminum
      silicate (MAS), on the properties of sodium caseinate (SC) dispersions and films.
      Moreover, the SC-MAS dispersions were evaluated for film coating of modified
      release tablets. The results showed that MAS addition led to particle
      flocculation and viscosity synergism in the SC-MAS dispersions. Exfoliated or
      intercalated nanocomposites of the SC-MAS films could be formed because of the
      molecular interaction of both components via hydrogen bonding. The puncture
      strength and elongation of the dry SC films decreased with increasing MAS ratios.
      However, MAS added enhanced the puncture strength of the wet films and reduced
      drug permeability and diffusivity across the films in acidic medium because of
      lower water uptake and denser matrix structure of the films. The SC-MAS
      dispersions showed strong potential for use as a film coating material with few
      defects in the coated acetaminophen (ACT) tablets. The ACT release of the coated
      tablets in acidic medium was modified by varying the MAS ratios and film coating
      levels. In addition, the SC-MAS coated tablets possessed sustained-release
      behavior for the drug under simulated gastrointestinal conditions. This finding
      indicates that the SC-MAS nanocomposite films can be applied as a tablet coating
      material to modify drug release.

PMID- 30184813
TI  - Antibacterial effect and biocompatibility of a novel nanostructured ZnO-coated
      gutta-percha cone for improved endodontic treatment.
AB  - This work explored a novel approach to enhance the antibacterial activity of
      commercial Gutta-percha (GP) cones, the most commonly used core filling materials
      used in endodontic treatment. The reported procedure involved an argon (Ar)
      plasma treatment (PT) of the GP cone surface, followed by the deposition of a ZnO
      thin film by magnetron sputtering. The resulting surfaces were evaluated for
      surface topography, antibacterial activity against Enterococcus faecalis and
      Staphylococcus aureus, and cytocompatibility with human osteoblastic cells. GP
      cones treated with NaOCl, a routine chair-side protocol, were also tested as
      reference. The deposition of a ZnO film on pristine GP cones increased its
      antibacterial activity. Cones pre-treated with Ar-plasma (PT) and coated with the
      ZnO thin film presented significantly higher antibacterial activity than that
      observed on the pristine and, also, compared to the ZnO coated cones. The higher
      antibacterial activity of PT + ZnO cones appears related to the major effects
      induced by the PT pre-treatment on the cone surface endowing the deposited ZnO
      film with a homogeneous nanostructured topography that greatly improved surface
      reactivity. The modified GP cones maintained an appropriate cytocompatibility
      with human cells. This novel approach provides ready-to-use cones with enhanced
      antibacterial activity, improving a strict asepsis protocol during endodontic
      treatment and preventing secondary endodontic infections.

PMID- 30184814
TI  - Characterization of chemically treated Ti-Zr system alloys for dental implant
      application.
AB  - Materials and surfaces developed for dental implants need to withstand
      degradation processes that take place in the oral cavity. Therefore, the aim of
      the study was to develop and evaluate the topographical, mechanical, chemical,
      electrochemical and biological properties of Ti-xZr alloys (x = 5, 10, and 15
      wt%) with two surface features (machined and double acid etched). Commercially
      pure titanium (cpTi) and Ti-6Al-4V alloy were used as controls. Surface
      characterization was performed using dispersive energy spectroscopy, X-ray
      diffraction, scanning electron microscopy, atomic force microscopy, profilometry
      and surface energy. The mechanical properties were assessed using Vickers
      microhardness, elastic modulus and stiffness. The electrochemical behavior
      analysis was conducted in a body fluid solution (pH 7.4). In addition, MC3T3-E1
      cells were used to determine the impact of material and surface treatment on cell
      morphology by SEM analysis. Data were analyzed by two-way ANOVA and Bonferroni
      test (alpha = 0.05). Ti-Zr alloys showed lower surface roughness, elastic modulus
      and stiffness, as well as higher hardness and surface energy when compared to
      cpTi. Ti-Zr system increased the polarization resistance values and significantly
      decreased the capacitance, corrosion current density (icorr), and passivation
      current density (ipass) values. The acid treatment increased the resistance and
      corrosion potential of the oxide layer. SEM data analysis demonstrated that Ti-Zr
      alloys displayed normal cell attachment/spreading and slightly changed cell
      morphology in the double etched surface. In conclusion, Zr addition and surface
      treatment altered surface, mechanical, biological and electrochemical properties
      of Ti material.

PMID- 30184815
TI  - An analysis on the potential of diode-pumped solid-state lasers for dental
      materials.
AB  - Material structure-property relationship is strongly related to the employed
      process technology. Over the past years, laser processing of engineering
      materials has been proposed in many fields and different uses for diode lasers
      have been found in dentistry. In this contest, the potential of GaN- and InGaN
      based laser diodes to cure dental materials was analysed. Two wavelengths of 405
      nm and 445 nm were used as heat or light sources for warm condensation of gutta
      percha, light transmission in dental posts and brackets or light curing of dental
      composites. Additive manufacturing approach was considered to fabricate 3D root
      analogues, suitable supports, positioning systems and moulds for optical
      measurements. A three-axis CAD/CAM system was implemented for positioning and
      aligning the laser beam. The ability of diode-pumped solid-state lasers to cure
      dental materials or to transmit light was compared to that of a traditional
      instrument. Temperature profile at the apex of an additive manufactured root
      canal sealed with gutta-percha, light transmission through translucent quartz
      fiber post or through aesthetic ceramic bracket, bending properties and
      morphological features of light cured dental composites (Gradia Direct - GC
      Corporation and Venus Diamond - Heraeus Kulzer) were measured. Results showed a
      very high potential of diode-pumped solid-state lasers to be used in endodontics,
      orthodontics and restorative dentistry.

PMID- 30184816
TI  - Electroactive biomaterial surface engineering effects on muscle cells
      differentiation.
AB  - Even though skeletal muscle cells can naturally regenerate as a response to
      insignificant tissue damages, more severe injuries can cause irreversible loss of
      muscle cells mass and/or function. Until now, cell therapies are not a good
      approach to treat those injuries. Biomaterials such as poly(vinylidene fluoride),
      PVDF, can improve muscle regeneration by presenting physical cues to muscle cells
      that mimic the natural regeneration environment. In this way, the ferroelectric
      and piezoelectric properties of PVDF offer new opportunities for skeletal muscle
      tissue engineering once the piezoelectricity is an electromechanical effect that
      can be used to provide electrical signals to the cells, upon mechanical
      solicitations, similar to the ones found in several body tissues. Thus, previous
      to dynamic experiments, it is important to determine how the surface properties
      of the material, both in terms of the poling state (positive or negative net
      surface charge) and of the morphology (films or fibers) influence myoblast
      differentiation. It was observed that PVDF promotes myogenic differentiation of
      C2C12 cells as evidenced by quantitative analysis of myotube fusion, maturation
      index, length, diameter and number. Charged surfaces improve the fusion of muscle
      cells into differentiated myotubes, as demonstrated by fusion and maturation
      index values higher than the control samples. Finally, the use of random and
      oriented beta-PVDF electrospun fibers scaffolds has revealed differences in cell
      morphology. Contrary to the randomly oriented fibers, oriented PVDF electrospun
      fibers have promoted the alignment of the cells. It is thus demonstrated that the
      use of this electroactive polymer represents a suitable approach for the
      development of electroactive microenvironments for effective muscle tissue
      engineering.

PMID- 30184817
TI  - Harnessing the pleiotropic effects of atorvastatin-fenofibrate combination for
      cardiovascular stents.
AB  - Atorvastatin and fenofibrate have been conventionally employed as lipid-lowering
      agents. They also exhibit beneficial effects in the treatment of endothelial
      dysfunction, oxidative stress and vascular inflammation due to their pleiotropic
      effects that include vasodilatory and anti-inflammatory effects. These
      pleiotropic effects may serve to overcome the drawbacks of late stent thrombosis
      and delayed endothelialization that plague conventional drug eluting stents.
      However, the combination has not been explored yet as therapeutic coatings in
      drug eluting stents. The present study aims to investigate the potential of
      atorvastatin-fenofibrate combination loaded in a biodegradable poly(l-lactide-co
      caprolactone) polymer film to inhibit thrombus formation and macrophage
      activation apart from exploring their effect on the proliferation of smooth
      muscle cells and endothelial cells. The dual drug-loaded polymer films were
      characterized by spectroscopy and calorimetry. In vitro studies revealed that the
      combination effectively retarded the proliferation of only smooth muscle cells
      but not the endothelial cells which augers well for stent applications where
      rapid re-endothelialization is preferred. Further, the dual drug-loaded films
      exhibited a marked decrease in the adhesion and activation of platelets and
      macrophages revealing the potent anti-thrombogenic and anti-inflammatory effects
      of the combination. The pleiotropic effects of the combination may be attributed
      to their ability to activate nitric oxide synthase in endothelial cells while
      mTOR levels remained unaltered by the combination.

PMID- 30184818
TI  - Biological effect of hydrothermally synthesized silica nanoparticles within
      crystalline hydroxyapatite coatings for titanium implants.
AB  - Development of functional coatings for artificial bone implants that strengthen
      the osseointegration and accelerate bone healing processes is urgently needed in
      the biomedical field. In this study we present biological effect of novel
      composite coatings with different concentration of silica nanoparticles within
      crystalline hydroxyapatite matrix (HAp-SiO2) synthesized on titanium under
      hydrothermal conditions. Samples were analyzed for their elemental composition,
      structure, bioactivity and in vitro cytotoxicity. The results indicate the
      formation and homogeneous distribution of silica nanoparticles on the surface of
      hexagonal hydroxyapatite (HAp) crystals. The coatings show improved bioactivity
      in comparison with pure HAp after 4 days of immersion in simulated body fluid
      (SBF). The responses of human osteoblast-like cells (MG-63) cultured onto the
      synthesized materials provide evidence that HAp-SiO2 composites exhibit good
      biocompatibility. We propose that this is because HAp-SiO2 composites favor
      biomineralization process with cell proliferation remaining unaffected,
      regardless of the amount of silica. Furthermore, SEM and fluorescence
      measurements demonstrate that HAp-SiO2 had positive effect on cell morphology,
      favoring cell adhesion.

PMID- 30184819
TI  - Ingenious pH-sensitive etoposide loaded folic acid decorated mesoporous silica
      carbon dot with carboxymethyl-betacyclodextrin gatekeeper for targeted drug
      delivery and imaging.
AB  - A new strategy is reported for the synthesis of label-free fluorescent mesoporous
      silica (MS) by the introduction of fluorescent carbon dots in the MSs (MSCDs) in
      this work. Etoposide (ETO) loaded MSCDs have been used as a drug model.
      Carboxymethyl beta-cyclodextrin (CbetaCD) used as a gatekeeper agent was attached
      to amine-functionalized MSCDs to retain ETO molecules inside the nanocarrier. In
      order to target the nanocarrier to the site of action, folic acid (FA) was
      grafted onto the MSCDs surface (FA-CbetaCD-MSCDs). The in vitro release of an
      entrapped ETO from the formulation in phosphate buffered saline (PBS) (pH 7.4)
      and citrate buffer (pH 5.4) was investigated. At neutral pH in PBS, the pores are
      blocked by CbetaCD which prevent premature ETO release. However, under the weakly
      acidic intercellular environment of the tumor, the amide bond can be partially
      hydrolyzed and consequently lead to the ETO release from the nanocarrier. The
      targeted and ETO-loaded FA-CbetaCD-MSCDs showed a higher growth inhibition
      towards FA-positive HeLa cells compared with FA-negative HepG2 cells, as
      demonstrated by comparison of in vitro cytotoxicity experiments. In addition, the
      CDs emission was used for the fluorescent microscopic imaging. Moreover,
      molecular docking and molecular dynamics simulations (MDS) were applied to
      examine the interactions of ETO molecules with the topoisomerase II (Top II). ETO
      molecules bind Top II with overall binding constants of 3.08 * 1010 M-1,
      according to docking results. Based on MDS results, ETO-Top II complex is formed
      through hydrophobic interactions.

PMID- 30184820
TI  - Biomimetic synthesis of silver nanoparticles using Matricaria chamomilla extract
      and their potential anticancer activity against human lung cancer cells.
AB  - Herbs having various natural substances can be utilized for the biosynthesis of
      Silver nanoparticles (AgNPs) and act as a stable, reliable and biocompatible
      alternative instead of the current physical and chemical approaches. It has been
      reported that Matricaria chamomilla possesses unique properties, especially anti
      cancerous effects. The objective of the current work was to assess the chemical
      characteristics and anticancer effects of biosynthesized AgNPs applying aqueous
      extracts of M. chamomilla against A549 lung cancer cells. UV-visible spectrum
      showed the maximum absorption of the biosynthesized AgNPs at 430 nm. The
      crystalline structure of biosynthesized AgNPs in optimal conditions was confirmed
      by XRD. Moreover, the presence of Ag as the ingredient element was exhibited via
      EDX analysis. FT-IR results also verified the AgNPs synthesis using a plant
      extract. The spherical shapes of the AgNPs with an average diameter size around
      45.12 nm and a zeta potential value of -34 mV were characterized using DLS, and
      confirmed through FE-SEM and TEM. In vitro cytotoxicity assay using MTT revealed
      that the biosynthesized AgNPs exhibited a dose- and time- dependent cytotoxic
      effect against A549 lung cancer cells. Moreover, the apoptotic effects of the
      AgNPs were demonstrated using DAPI staining, real-time PCR and flow cytometry.
      According to these findings, using M. chamomilla in combination with AgNPs via
      green-synthesis approach may be an efficient strategy for effective treatment of
      lung cancer.

PMID- 30184821
TI  - IRMOF-3: A fluorescent nanoscale metal organic frameworks for selective sensing
      of glucose and Fe (III) ions without any modification.
AB  - The amine functionalized isoreticular metal-organic framework-3 (IRMOF-3) is
      synthesized by hydrothermal method. Till now, it's widely used in the area of gas
      separation, adsorption, and catalysis due to large surface area, structural
      stability, and tunability. Here, we have reported the use of fluorescent
      nanoscale IRMOF-3 for highly selective detection of glucose as well as Fe3+ ions
      without any modification. This is due to NH2 and COOH groups are present on the
      surface of IRMOF-3 to bind cis-diols of the glucose molecule via host-guest
      interaction, and Fe3+ ions via ligand to metal charge transfer. The Synthesized
      IRMOF-3 has average diameter of 160 +/- 20 nm and interestingly possess deep blue
      fluorescent emission spectra at 460 nm with quantum yield 17.3%. Using
      fluorometric assay, the limit of detection (LOD) of glucose and Fe3+ ions was
      found to be 0.56 MUM and 4.2 nM respectively. More importantly, the synthesized
      IRMOF-3 is also utilized for detection of glucose and Fe3+ ions in bio
      environmental samples.

PMID- 30184822
TI  - Incorporation of Ce3+ ions into dodecatungstophosphoric acid for the production
      of biodiesel from waste cooking oil.
AB  - A series of cerium-exchanged dodecatungstophosphates CexH3-3xPW12O40 (CexH3-3xPW,
      x = 0.4, 0.6, 0.7, 0.8, 0.9, and 1.0) were designed and characterized by Fourier
      transform infrared spectroscopy (FT-IR), pyridine adsorption IR spectra, X-ray
      diffraction (XRD), and temperature programmed desorption of ammonia (NH3-TPD).
      The activity of these catalysts was evaluated for the generation of biodiesel
      from waste cooking oil (WCO) with 27 wt% of free fatty acids (FFAs) and 1 wt% of
      water. Compared to theri parent H3PW12O40, CexH3-3xPW showed higher activity for
      esterification of FFAs and transesterification of triglyceride to mono-alkyl
      esters of fatty acids (FAMEs) in one-pot. The acidic properties of CexH3-3xPW
      depended on the amount of Ce3+ ions in the secondary structure of Keggin
      heteropolyacids, while conversion of triglycerides and FFAs depended on their
      increasing acid contents. Among CexH3-3xPW, Ce0.7H0.9PW showed significant
      activity due to its high Bronsted acidity and Lewis acidity with 98% conversion
      of WCO and almost 100% selectivity to FAME at the molar ratio of methanol to WCO
      = 21:1 and 65  degrees C for 12 h. The reaction adhered to first-order kinetics
      with the activation energy (Ea) of 71 kJ/mol and the frequency factor (A) of 1.8
      * 108 min-1, while the reaction rates were not influenced by the internal mass
      transport. The catalyst behaved as a heterogeneous catalyst, which can achieve
      the regeneration and be used more than five runs but without obvious decrease in
      activity. The characteristics of the WCO methyl ester were found to be close to
      the engine requirement.

PMID- 30184823
TI  - Synthesis, characterization and in vitro analysis of alpha-Fe2O3-GdFeO3 biphasic
      materials as therapeutic agent for magnetic hyperthermia applications.
AB  - The use of gadolinium orthoferrite for biomedical application like as contrast
      agents for magnetic resonance imaging (MRI) has been found to be very promising
      due to its fascinating properties. The present study focuses on the determination
      of the effect of the gadolinium concentration in the formation biphasic alpha
      Fe2O3-GdFeO3 for hyperthermia applications. An in-situ sol-gel technique was
      adopted for the synthesis of biphasic orthoferrites with four different
      gadolinium concentrations. The XRD analysis confirmed the formation of gadolinium
      orthoferrites after heat treatment at 1000  degrees C, 1100  degrees C, and 1200 
      degrees C. The presence of alpha-Fe2O3 in trace amounts was observed in the
      materials with low gadolinium concentrations. VSM (Vibrating-sample magnetometer)
      analysis was performed to ensure the magnetic properties of the materials, which
      were found to be weakly ferromagnetic. The biocompatibility of the materials was
      investigated through MTT assay and no cytotoxic effect was observed. The
      assessment of heating ability of the materials was performed under an alternating
      magnetic field using an induction heating instrument and all the samples showed
      temperature rise in the range of hyperthermia temperature with a maximum
      temperature of 55.71  degrees C in 6 min. The heating experiments at 44  degrees
      C in the absence of samples established the vulnerability of cancer cells as
      compared to normal cells.

PMID- 30184824
TI  - Electrochemical sensing of cholesterol by molecularly imprinted polymer of
      silylated graphene oxide and chemically modified nanocellulose polymer.
AB  - Silylated Graphene oxide-grafted-chemically modified nanocellulose (Si-GO-g-CMNC)
      is fabricated for selective sensing of Cholesterol. Zinc oxide (ZnO) incorporated
      in chemically modified nanocellulose (CMNC) for enhancing the conducting nature.
      The sensitivity of sensor was checked by modifying the glassy carbon electrode
      surface (GCE) with Si-GO-g-CMNC and the electro chemical studies were conducted
      with cyclic voltammetry (CV) and differential pulse voltammetry (DPV). The
      physical and electrical properties of the sensor were analyzed by FTIR, Raman
      Spectroscopy, XRD, SEM, EDS and AFM techniques. CV analysis of [FeCN6]3-/4-
      showed a redox potential difference of 0.156 mV on the bare GCE, while for the
      electrode coated with MIP, redox peak current increased to 0.2319 mV. The values
      of limit of detection (LOD) obtained as 7.4 MUmol/L for the detection range of
      5.18-25.9 MUmol/L. The optimum response time and optimum pH were found to be 10
      min and 7.4, respectively. DPV analysis revealed good linearity in the
      cholesterol sensing range of 0.6475-10.360 * 103 MUmol/L with LOD value 98.6
      MUmol/L.

PMID- 30184825
TI  - Strain and damage-sensing performance of biocompatible smart CNT/UHMWPE
      nanocomposites.
AB  - Herein, we report strain- and damage-sensing performance of biocompatible smart
      CNT/UHMWPE nanocomposites for the first time. CNT/UHMWPE nanocomposites are
      fabricated by solution mixing followed by compression molding. The surface
      morphology, microstructural properties, thermal decomposition and stability,
      glass transition temperature and thermal conductivity of the nanocomposites are
      characterized. The degree of crystallinity of CNT/UHMWPE nanocomposites is found
      to have a maximum value of 52% at 0.1 wt% CNT loading. The degree of
      crystallinity influences the mechanical properties of the CNT/UHMWPE
      nanocomposites. The electrical percolation threshold is achieved at 0.05 wt% of
      CNT and it follows a two dimensional conductive network according to percolation
      theory. The piezoresistive response of CNT/UHMWPE nanocomposites is demonstrated
      with a gauge factor of ~2.0 in linear elastic regime and that in the range of 3.8
      96.0 in inelastic regimes for 0.05 wt% of CNT loading. A simple theoretical model
      is also developed to predict the resistivity evolution in both elastic and
      inelastic regimes. High sensitivity of CNT/UHMWPE nanocomposites coupled with
      linear piezoresistive response up to 100% strain demonstrates their potential for
      application in artificial implants as a self-sensing material.

PMID- 30184826
TI  - Antiviral activity of multifunctional composite based on TiO2-modified
      hydroxyapatite.
AB  - An antiviral activity of TiO2-modified hydroxyapatite composite (HA/TiO2) had
      been investigated. The HA/TiO2 composite (HA50:Ti50) was prepared by a solid
      state reaction method followed by calcination at 650  degrees C for 2 h. Phase
      formations and morphologies of the obtained HA/TiO2 composite powders were
      determined using XRD and SEM. XRD result confirmed that HA/TiO2 composite was
      successfully prepared. SEM revealed small crystals of anatase TiO2 embedded in
      larger HA crystals. A strong antiviral activity against H1N1 Influenza A Virus
      was observed at 0.5 mg/ml concentration of the composite under the UV irradiation
      for 60 min. It showed the highest rate of reducing virus titer approximately more
      than 2 log/h. Results obtained from this study indicated that HA/TiO2 composite
      could be a promising material to be used as antimicrobial filtration applications
      such as in face masks.

PMID- 30184827
TI  - Electrospinning and electrospray of bio-based and natural polymers for
      biomaterials development.
AB  - Over nearly 70 years, polymers have revolutionized the global economy,
      manufacturing and, mainly, the fields which require biocompatible materials, as
      food technology and packaging, controlled drug delivery, tissue engineering,
      regenerative medicine, wound dressing, anti-allergy textiles, and personal care.
      While new high-performance polymers were produced from fossil-based sources to
      meet the functional performance demands of new applications, Earth has been
      polluted by the operation of factories that released CO2 to the atmosphere during
      the production of synthetic polymers. At the same time, biocompatible and
      biodegradable alternatives were being required to meet specific needs of a range
      of applications. In this paper, we reviewed the use of electrospun/electrospray
      bio-based and natural polymers in the last ten years in food technology and smart
      packaging, food additives, antimicrobial packaging, enzyme immobilization, tissue
      engineering, drug delivery, wound dressing, anti-allergy fibers from milk, and
      faux meat. Also, we reviewed the use of ionic liquids and click chemistry
      techniques as alternatives for modification and functionalization of
      electrospun/electrospray bio-based and natural polymers.

PMID- 30184828
TI  - Polyester-based nanoparticles for nucleic acid delivery.
AB  - Gene therapy is promising for the treatment of inherited diseases and complex
      diseases such as chronic infections and cancer. The advancement in science and
      technology has extended the scope of gene therapy from gene transfer to the
      delivery of a variety of nucleic acids such as mRNA, antisense oligonucleotides
      (ASOs), siRNA and miRNA. Nanoparticle delivery systems can efficiently protect
      the nucleic acids from enzymatic degradation and immune recognition, facilitate
      intracellular transportation and assist the nucleic acid in escaping from renal
      and hepatic clearance, thus achieve sustained delivery to the target tissue.
      Aliphatic polyesters such as PLA, PLGA, PCL and PHB have entered clinic for
      decades for making implantable medical devices such as surgical meshes, sutures,
      screws, tissue repair patches and filling agents; and have been actively
      investigated for drug and gene delivery due to the excellent degradability and
      biocompatibility. Cationic polyester nanospheres, micelles and dendrimers which
      can efficiently condense and deliver nucleic acids have been synthesized via
      methods such as physical mixing, chemical conjugation and copolymerization of
      polyesters and cationic molecules.

PMID- 30184829
TI  - Electrospun three-dimensional aligned nanofibrous scaffolds for tissue
      engineering.
AB  - Engineered tissue constructs rely on biomaterials as support structures for
      tissue repair and regeneration. Among these biomaterials, polyester biomaterials
      have been widely used for scaffold construction because of their merits such as
      ease in synthesis, degradable properties, and elastomeric characteristics. To
      mimic the aligned structures of native extracellular matrix (ECM) in tissues such
      as nerve, heart and tendon, various polyester materials have been fabricated into
      aligned fibrous scaffolds with fibers ranging from several nanometers to several
      micrometers in diameter by electrospinning in a simple and reproducible manner.
      These aligned fibrous scaffolds, especially the three-dimensional (3D) aligned
      nanofibrous scaffolds have emerged as a promising solution for tissue
      regeneration. Compared with two-dimensional (2D) scaffolds, the 3D aligned
      nanofibrous scaffolds provide another dimension for cell behaviors such as
      morphogenesis, migration and cell-cell interactions, which is important in
      regulating the stem cell fate and tissue regeneration. In this review, we provide
      an extensive overview on recent efforts for constructing 3D aligned polyester
      nanofibrous scaffolds by electrospinning, then the results of cell-specific
      functions dependent on such physical and chemical cues, and discuss their
      potentials in improving or restoring damaged tissues.

PMID- 30184830
TI  - The bithorax complex: control of segmental identity.

PMID- 30184831
TI  - On the minimization of adjacency effects in SeaWiFS primary data products from
      coastal areas.
AB  - The minimization of adjacency effects (AE) in SeaWiFS primary products at the
      Aqua Alta Oceanographic Tower (AAOT) was investigated using sample images
      concurrent with in situ measurements. The validation exercise was performed with
      the NASA SeaDAS processing scheme ingesting original SeaWiFS data and
      alternatively SeaWiFS top-of-atmosphere data corrected for AE, and additionally
      including and excluding the default turbid water (TW) correction algorithm.
      Results show overestimates of the TW contributions partially compensating for AE.
      The analysis also suggests that intra-annual biases observed in SeaWiFS
      radiometric products at the AAOT may result from a misinterpretation of the NIR
      atmospheric signal as water contribution in data acquired in winter, and from
      uncompensated AE in data acquired in summer.

PMID- 30184832
TI  - Dynamic optical control of near-field radiative transfer.
AB  - Dynamic control of radiative heat transfer is of fundamental interest as well as
      for applications in thermal management and energy conversion. However, realizing
      high contrast control of heat flow without moving parts and with high temporal
      frequencies remains a challenge. Here, we propose a thermal modulation scheme
      based on optical pumping of semiconductors in near-field radiative contact.
      External photo-excitation of the semiconductor emitters leads to increases in the
      free carrier concentration that in turn alters the plasma frequency, resulting in
      modulation of near-field thermal radiation. The temporal frequency of the
      modulation can reach hundreds of kHz limited only by the recombination lifetime,
      greatly exceeding the bandwidth of methods based on temperature modulcation.
      Calculations based on fluctuational electrodynamics show that the heat transfer
      coefficient between two silicon films can be tuned from near zero to 600 Wm-2K-1
      with a gap distance of 100 nm at room temperature.

PMID- 30184833
TI  - Distinguishing Fabry-Perot from guided resonances in thin periodically-textured
      silicon absorbers.
AB  - Periodic texturing is one of the main techniques for light-trapping in thin-film
      solar cells. Periodicity allows for the excitation of guided modes in the
      structure and, thus, largely enhances absorption. Understanding how much a guided
      resonance can increase the absorption is therefore of great importance. There is
      a common method to understand if an absorption peak is due to the excitation of a
      guided mode, using dispersion diagrams. In such graphs, a resonance is identified
      as the intersection of a guided-mode-line of a uniform waveguide (with the same
      optical thickness as the grating structure) with the center of a Brillouin zone
      of the grating. This method is unfortunately not reliable when the grating height
      is comparable with the thickness of the wave-guide, or when the thickness of the
      wave-guide is much larger than the wavelength. In this work, we provide a novel
      approach to calculate the contribution of a guided resonance to the total
      absorption in a periodic waveguide, without using the dispersion diagram. In this
      method, the total electric field in the periodic structure is described by its
      spatial frequencies, using a Fourier expansion. Fourier coefficients of the
      electric field were used to calculate the absorption of each diffraction order of
      the grating. Rigorous numerical calculations are provided to support our
      theoretical approach. This work paves the way for a deeper understanding of light
      behavior inside a periodic structure and, consequently, for developing more
      efficient light-trapping techniques for solar cells applications.

PMID- 30184834
TI  - Optical design of spectrally selective interlayers for perovskite/silicon
      heterojunction tandem solar cells.
AB  - Monolithic perovskite/c-Si tandem solar cells have the potential to exceed the
      Shockley-Queisser limit for single junction solar cells. However, reflection
      losses at internal interfaces play a crucial role for the overall efficiency of
      the tandem devices. Significant reflection losses are caused by the charge
      selective contacts which have a significantly lower refractive index compared to
      the absorber materials. Here, we present an approach to overcome a significant
      part of these reflection losses by introducing a multilayer stack between the top
      and bottom cell which shows spectrally selective transmission/reflection
      behavior. The layer stack is designed and optimized by optical simulations using
      transfer matrix method and a genetic algorithm. The incident sun light is split
      into a direct part and an isotropic diffuse part. The tandem solar cell with
      interlayer shows an absolute improvement of short-circuit current density of 0.82
      mA/cm2.

PMID- 30184835
TI  - Optical modeling of structured silicon-based tandem solar cells and module
      stacks.
AB  - Silicon-based tandem solar cells and modules are complex systems that require
      optical modeling for the optimization towards highest efficiencies. The fact that
      such devices typically incorporate surface structures of different optical
      regimes poses high requirements to the involved simulation tools. The OPTOS
      formalism is ideally suited to deal with such complexity. Within this work OPTOS
      is extended in order to calculate the layer resolved absorptance in silicon-based
      tandem solar cells and module stacks. After describing the relevant mathematical
      details, a good agreement between OPTOS absorptance simulation results and EQE
      measurements of the current 33.3% record efficiency III-V on silicon two-terminal
      tandem solar cell is found. Furthermore, a detailed loss analysis is performed
      for an exemplary perovskite silicon solar cell with and without module
      encapsulation. The comparison reveals a lower photocurrent density for the module
      stack due to increased reflectance and absorption in the EVA.

PMID- 30184836
TI  - Copper oxide-modified graphene anode and its application in organic photovoltaic
      cells.
AB  - Graphene is an ideal substitute for indium tin oxide electrode in organic
      photovoltaic (OPV) devices, due to its outstanding electrical, optical, chemical
      and mechanical properties. However, the graphene electrode suffers from work
      function mismatch with common hole injection layer and intrinsic hydrophobic
      property. Here, CuxO is proposed to modify monolayer graphene in order to
      increase the work function of graphene (from 4.45 to 4.76 eV) and decrease the
      water contact angle (from 88 degrees  to 59 degrees ). Then, the OPV devices
      based on the CuxO modified graphene anode are fabricated successfully, and power
      conversion efficiency (PCE) is enhanced from 4.00 +/- 0.44 to 5.23 +/- 0.47%.
      Furthermore, the ternary blended polymer solar cell is fabricated by adding a
      small molecular material 1, 2, 5-thiadiazole-fused 12-ring polyaromatic
      hydrocarbon into the active layer, and the PCE is improved to 6.03 +/- 0.53%, due
      to the enhanced absorption and depressed recombination inside the active layer.

PMID- 30184837
TI  - Self-adaptive radiative cooling based on phase change materials.
AB  - With the ability of harvesting the coldness of universe as a thermodynamic
      resource, radiative cooling technology is important for a broad range of
      applications such as passive building cooling, refrigeration, and renewable
      energy harvesting. However, all existing radiative cooling technologies utilize
      static structures, which lack the ability of self-adaptive tuning based on
      demand. Here we present the concept of self-adaptive radiative cooling based on
      phase change materials such as vanadium dioxide. We design a photonic structure
      that can adaptively turn 'on' and 'off' radiative cooling, depending the ambient
      temperature, without any extra energy input for switching. Our results here lead
      to new functionalities of radiative cooling and can potentially be used in a wide
      range of applications for the thermal managements of buildings, vehicles and
      textiles.

PMID- 30184838
TI  - Field-enhancing photonic devices utilizing waveguide coupling and plasmonics - a
      selection rule for optimization-based design.
AB  - This paper describes a systematic design study of periodic gold-nanostrip arrays
      placed on a thin film aimed at enhancing the electric field inside the film when
      irradiated by light. Based on the study, a "selection rule" is proposed, which
      provides optimization-based design methods with an a priori choice between field
      enhancement dominated by coupling to guided modes, by plasmonic near-field
      enhancement or by a mix hereof. An appropriate choice of wavelength and grating
      period is shown to selectively suppress or include waveguiding effects for the
      optimized designs. The validity of the selection rule is demonstrated through a
      numerical topology optimization study in which gold nanostrips are optimized for
      electric-field enhancement in an erbium-doped TiO2 thin film, targeting increased
      spectral upconversion in the erbium ions. The obtained designs exhibit waveguide
      excitation within the predicted intervals and, for light polarized
      perpendicularly to the strips, plasmonic response outside.

PMID- 30184839
TI  - Raman spectra and optical properties of the chalcogen-hyperdoped silicon: a first
      principles study.
AB  - The Raman peaks observed in the ultrafast-laser induced chalcogen-hyperdoped Si
      are assigned to different configurations of defects formed in crystal Si. The
      disappearance of the Raman peaks of the chalcogen-hyperdoped Si after thermal
      annealing is attributed to the formation of polymers, which cannot display any
      Raman peaks except the strong peak of crystal Si. The imaginary parts of the
      dielectric functions indicate that sub-bandgap absorptions are also reduced when
      the chalcogen atoms combine to form a polymer. The reductions of the sub-bandgap
      absorptions are different for S- and Se-hyperdoped Si, which can give a good
      explanation for their different variations of infrared absorptance at the same
      annealing conditions.

PMID- 30184840
TI  - Detection of periodic structures through opaque metal layers by optical
      measurements of ultrafast electron dynamics.
AB  - We report on femtosecond optical pump-probe measurements of ultrafast electron
      dynamics to detect the presence of gratings buried underneath optically opaque
      gold layers. Electron energy diffusion and cooling are found to be strongly
      affected by the presence and type of metal buried below the gold layer. As a
      result, the spatially periodic buried grating is encoded on the electron
      temperature near the top surface, leading to a spatially periodic modulation of
      the optical properties near the gold surface from which a delayed probe pulse can
      be diffracted. Our measurements show that these effects may be useful for optical
      detection and alignment applications in semiconductor device manufacturing.

PMID- 30184841
TI  - Red/green/blue LD mixed white-light communication at 6500K with divergent
      diffuser optimization.
AB  - Enabling laser white-lighting at a correlated color temperature (CCT) of 6500K
      with the use of only red/green/blue (RGB) tri-color laser diodes (LDs) is
      demonstrated, which can further perform wavelength division multiplexing (WDM)
      communication with a high-spectral-usage 16 QAM-OFDM data stream at 11.2 Gbps
      over 0.5 m. The sampling rate of encoded data is optimized to avoid the aliasing
      effect and to effectively amplify the signal with high on/off extinction and
      modulation depth. Proper oversampling can decrease the peak-to-average power
      ratio (PAPR) of the OFDM data and filter out unwanted noise. There are also six
      different diffusers used to diverge the white-light mixed by the RGB LD beam. By
      analyzing the color-casting transmittance, surface roughness, CCT uniformity,
      divergent angle of the diffuser, and the data transmission capacity, the frosted
      glass (FG2.8) diffuser with high transmittance diverges the white light with the
      divergent angle of +/- 20 degrees  and supports the highest data rate of 14 Gbps
      over 0.5 m. To fit the day-light CCT, the blue LD power at an optimized bias
      current is further attenuated with a 0.6-optical density filter for reducing CCT
      from 100000K to 6500K; however, such an adjustment also degrades the SNR ratio to
      sacrifice the achievable data rate of the blue LD. The polycarbonate (PC1.5)
      diffuser with proper surface roughness diverged white-light exhibits the best CCT
      uniformity and a divergent angle of +/- 30 degrees  but supports a data rate of
      only 6.4 Gbps over 0.5 m. The poly (methyl methacrylate) PMMA1.5 diffuser
      scatters the white light with the largest angle of +/- 40 degrees ; however, the
      data rate also decreases to 4.8 Gbps over 0.5 m.

PMID- 30184842
TI  - Numerical study of Bragg CDI on thick polycrystalline specimens.
AB  - Bragg coherent diffraction imaging (BCDI) is a powerful X-ray imaging technique
      for crystalline materials, providing high resolution maps of structure and
      strain. The technique is typically used to study a small isolated object, and is
      in general not compatible with a bulk polycrystalline sample, due to overlap of
      diffraction signals from various crystalline elements. In this paper, we present
      an imaging method for bulk samples, based on the use of a coherent source. The
      diffracted X-ray beam from a grain or domain of choice is magnified by an
      objective before being monitored by a 2D detector in the far field. The
      reconstruction principle is similar to the case of BCDI, while taking the
      magnification and pupil function into account. The concept is demonstrated using
      numerical simulations and reconstructions. We find that by using an object-lens
      distance shorter than the focal length, the numerical aperture is larger than in
      a traditional imaging geometry, and at the same time the setup is insensitive to
      small phase errors by lens imperfections. According to our simulations, we expect
      to be able to achieve a spatial resolution smaller than 20 nm when using the
      objective lens in this configuration.

PMID- 30184843
TI  - Mesoscale surface plasmons: modelling and imaging using near-field scanning
      optical microscopy.
AB  - Meso-scale plasmons are supported by structures with dimensions on the order of
      tens of plasmon wavelengths. Metal structures at this length-scale are promising
      for the design and engineering of structures to direct the flow of optical energy
      and generate high intensity, localized electric fields. The near-field optical
      properties of mesoscale crystalline gold plates were examined using near-field
      scanning optical microscopy with a focus on the effects of modifying morphology
      and excitation conditions. Excitation of surface plasmon polaritons (SPPs) at
      plate edges and their subsequent propagation and interference as radial waves
      across the surface results in nodes of enhancement of the near-field on the plate
      surface at specific positions within the plate. The spatial position of the near
      field enhancement may be directed by controlling either, or both, the boundary
      conditions (plate shape) and polarization of the excitation light.

PMID- 30184844
TI  - Studies on different primaries for a nearly-ultimate gamut in a laser display.
AB  - In using a laser light source, it becomes possible to realize an ultra-wide
      display gamut that approaches the human color vision limit. This paper introduces
      a method for extremely large gamut optimization for different primary numbers,
      and it offers a primary set that produces a nearly ultimate gamut. Considering
      display lightness, we calculated wavelength selection and lightness design of a
      display with 3-9 primaries in the CIELAB uniform color space (UCS) by optimizing
      the coverage of the optimal color gamut. Theoretically the maximum gamut area of
      a laser display with 3-12 primaries in the CIE xy and CIE u'v' chromaticity
      diagrams is also calculated for comparison. We recommend 6 primaries as a
      reasonable choice, since the coverage reaches 97.6% of the optimal color. Taking
      into account the luminance efficacy of radiation (LER) and feasible laser
      wavelengths in practice, we get a practical design of wavelengths and power for a
      laser projection display with 6 primaries, which covers 96.6% of the optimal
      color gamut.

PMID- 30184845
TI  - Structured spin angular momentum in highly focused cylindrical vector vortex
      beams for optical manipulation.
AB  - We investigate the spin properties of a family of cylindrical vector vortex beams
      under a focusing condition. The spin-orbit interaction is demonstrated by
      comparing the energy flow and spin flow density of the focused field to those of
      the incident field. This spin-orbit interaction is analyzed to construct the
      desired distribution of spin angular momentum for optical manipulation. The
      structured spin angular momentum of the focused field can transfer to the optical
      torque for the non-magnetic absorptive particle. The influences of polarization
      topological charge, vortex topological charge and wavelength on optical torque in
      the hot-spot of focused field are summarized for three typical particles. Such
      results may be exploited in practical optical manipulation, particularly for
      optically induced rotations.

PMID- 30184846
TI  - Conservation of orbital angular momentum for high harmonic generation of
      fractional vortex beams.
AB  - This work demonstrates conservation of average orbital angular momentum for high
      harmonic generation of fractional vortex beams. High harmonics are generated in
      reflected light beams in a three-dimensional particle-in-cell simulation. The
      average orbital angular momentum of the beam is calculated when a relativistic
      linearly polarized fractional vortex beam impinges on a solid foil. The harmonic
      generation progress can be well explained by using the vortex oscillating mirror
      model. Both simulation and theoretical analysis show that the average orbital
      momentum of the nth harmonic is n times that of the fundamental frequency beam.
      This provides evidence that the average orbital angular momentum obeys momentum
      conservation during the harmonic generation of fractional vortex beams.

PMID- 30184847
TI  - Concentration dependent optical transition probabilities in ultra-small
      upconversion nanocrystals.
AB  - Transition probability is of vital importance for luminescence process, whereas
      the effects of doping concentration have not been explored in the Er3+:NaGdF4. In
      this work, we investigate the radiative transition probabilities of Er3+ highly
      doped NaGdF4 sub 10 nm nanocrystals using J-O theory. It is found that the
      transition probabilities vary with changing Er3+ concentration, especially
      altering the ratio of Er3+ 2H11/2 to 4S3/2 level, which is highly useful for
      optical thermometers as they are thermally coupled. To validate the concentration
      dependent transition probabilities, significant enhancements of upconversion
      luminescence are achieved by epitaxial growth of the inert shell, and thermal
      sensing behaviors are investigated using the improved samples.

PMID- 30184848
TI  - Collision between a dark soliton and a linear wave in an optical fiber.
AB  - We report an experimental observation of the collision between a linear wave
      propagating in the anomalous dispersion region of an optical fiber and a dark
      soliton located in the normal dispersion region. This interaction results in the
      emission of a new frequency component whose wavelength can be predicted using
      phase-matching arguments. The measured efficiency of this process shows a strong
      dependency with the soliton grayness and the linear wave wavelength, and is in a
      good agreement with theory and numerical simulations.

PMID- 30184849
TI  - Direct measurement of radiation pressure and circulating power inside a passive
      optical cavity.
AB  - A mechanical force sensor coupled to two optical cavities is developed as a
      metrological tool. This system is used to generate a calibrated circulating
      optical power and to create a transfer standard for externally coupled optical
      power. The variability of the sensor as a transfer standard for optical power is
      less than 2%. The uncertainty in using the sensor to measure the circulating
      power inside the cavity is less than 3%. The force measured from the mechanical
      response of the sensor is compared to the force predicted from characterizing the
      optical spectrum of the cavity. These two forces are approximately 20% different.
      Potential sources for this disagreement are analyzed and discussed. The sensor is
      compact, portable, and can operate in ambient and vacuum environments. This
      device provides a pathway to novel nanonewton scale force and milliwatt scale
      laser power calibrations, enables direct measurement of the circulating power
      inside an optical cavity, and enhances the sensitivity of radiation pressure
      based optical power transfer standards.

PMID- 30184850
TI  - Identifying modulation formats through 2D Stokes planes with deep neural
      networks.
AB  - A lightweight convolutional (deep) neural networks (CNNs) based modulation format
      identification (MFI) scheme in 2D Stokes planes for polarization domain
      multiplexing (PDM) fiber communication system is proposed and demonstrated.
      Influences of the learning rate of CNN is discussed. Experimental verifications
      are performed for the PDM system at a symbol rate of 28GBaud. Six modulation
      formats are identified with a trained CNN from images of received signals. They
      are PDM-BPSK, PDM-QPSK, PDM-8PSK, PDM-16QAM, PDM-32QAM, and PDM-64QAM. By taking
      advantage of computer vision, the results show that the proposed scheme can
      significantly improve the identification performance over the existing
      techniques.

PMID- 30184851
TI  - All-fiber, thermo-optic liquid level sensor.
AB  - This paper proposes an all-optical-fiber sensor for continuous measurements of
      liquid levels. The proposed sensor utilizes an optically absorbing vanadium doped
      optical fiber, which is configured as a long-gauge, optically-heated, fiber
      optic, Fabry-Perot interferometer that is immersed into the measured liquid. The
      sensor is excited cyclically by a medium-power 980 nm optical source, which
      induces periodic temperature variation and, consequently, optical path length
      modulation within the vanadium doped fiber. The amplitude of this path length
      variation depends on the liquid level and is measured by an interferometric
      approach. The relation between the liquid level and the amplitude of optical path
      length modulation caused by the fiber's temperature variation were investigated
      analytically, and the theoretical model proved to be in good agreement with the
      experimental results. Two versions of level sensors are demonstrated
      experimentally, the first with single-side optical heating power delivery and
      0.45 m measurement range, and the second with dual-side power delivery and 1 m of
      operational measurement span. Experimental measurement level resolutions achieved
      for 0.45 m and 1m operational measurement span were approximately 2 and 3 mm,
      respectively. The simple and efficient design of sensor and signal interrogation
      system, the latter is based solely on a few widely available telecom components,
      provides straightforward opportunities for use of the proposed system in a
      variety of industrial applications.

PMID- 30184852
TI  - Quantitative SERS by electromagnetic enhancement normalization with carbon
      nanotube as an internal standard.
AB  - Quantitative surface-enhanced Raman scattering (SERS) in practical applications
      still remain unresolved, mainly due to low reproducibility relying on the quality
      of the SERS substrates. In this paper, a carbon nanotube and Ag nanoparticles
      composite (CNT/AgNPs) is reported, and the carbon nanotube is as an internal
      standard for the calibration of SERS intensity of analyte molecules. The
      quantification of analyte molecules rhodamine 6G (R6G) is demonstrated in an
      aqueous solution with the concentration of 10-9 to 10-7 M. Raman mapping is used
      to investigate the stability of SERS spectra in a large scanning area, and the
      corresponding relative standard deviation (RSD) is calculated. SERS mapping
      reveals that the uniformity of Raman enhancement is improved through the build-in
      calibration with 2D Raman peak of CNT. Meanwhile, CNT/AgNPs samples are used to
      detect N2 in natural air, indicating that such self-calibration method can
      improve the reliability of the SERS analysis.

PMID- 30184853
TI  - Waveguide-integrated mid-infrared plasmonics with high-efficiency coupling for
      ultracompact surface-enhanced infrared absorption spectroscopy.
AB  - Waveguide-integrated plasmonics is a growing field with many innovative concepts
      and demonstrated devices in the visible and near-infrared. Here, we extend this
      body of work to the mid-infrared for the application of surface-enhanced infrared
      absorption (SEIRA), a spectroscopic method to probe molecular vibrations in small
      volumes and thin films. Built atop a silicon-on-insulator (SOI) waveguide
      platform, two key plasmonic structures useful for SEIRA are examined using
      computational modeling: gold nanorods and coaxial nanoapertures. We find
      resonance dips of 90% in near diffraction-limited areas due to arrays of our
      structures and up to 50% from a single resonator. Each of the structures is
      evaluated using the simulated SEIRA signal from poly(methyl methacrylate) and an
      octadecanethiol self-assembled monolayer. The platforms we present allow for a
      compact, on-chip SEIRA sensing system with highly efficient waveguide coupling in
      the mid-IR.

PMID- 30184854
TI  - High-temperature stable pi-phase-shifted fiber Bragg gratings inscribed using
      infrared femtosecond pulses and a phase mask.
AB  - Type II pi-phase-shifted Bragg gratings stable up to ~1000 degrees C are written
      inside a standard single mode silica optical fiber (SMF-28) with infrared
      femtosecond pulses and a special phase mask. Inscription through the protective
      polyimide fiber coating is also demonstrated. The birefringence of the Bragg
      gratings and, as a result, the polarization dependence of their spectra are
      strongly affected by the femtosecond laser polarization. Using optimized writing
      conditions, the full width at half maximum of the pi-phase-shifted passband
      feature can be ~30 pm in transmission, while the polarization-dependent shift of
      its central wavelength can be less than 8 pm, for a 7 mm long grating structure.
      This makes such gratings a unique tool for high-resolution measurements of
      temperature, load and vibration in extreme temperature environments.

PMID- 30184855
TI  - Towards power-efficient long-reach underwater wireless optical communication
      using a multi-pixel photon counter.
AB  - The transmission distance of underwater wireless optical communication (UWOC) is
      severely limited by the rapid decay of light intensity in water. Power-efficient
      pulse position modulation (PPM) and ultra-sensitive multi-pixel photon counter
      (MPPC) open the door toward designing long-reach UWOC systems. In this paper, a
      46-m UWOC system based on PPM and MPPC was proposed and experimentally
      demonstrated with ultra-low transmitting power into the underwater channel. Clear
      eye diagrams without any slot error for ten different PPM signals were obtained
      in the 46-m experiment with data rates of Mbps level. The received optical power
      was as low as -39.2 dBm for the 10-MHz 4-PPM signal, when the laser worked under
      the stimulated state. Meanwhile, the received optical power can be reduced to 
      62.8 dBm, for the 5-MHz 64-PPM signal when the laser worked under the spontaneous
      state.

PMID- 30184856
TI  - Phase-shifting-free resolution enhancement in digital holographic microscopy
      under structured illumination.
AB  - In this paper, we present a phase-shifting-free method to improve the resolution
      of digital holographic microscopy (DHM) under the structured illumination (SI).
      The SI used in the system is different from the traditional SI for it is free of
      the visible structure due to two illumination lights with orthogonal polarization
      states. To separate the recorded information and also retrieve the object phase,
      two reference beams with different carrier frequencies and orthogonal
      polarization states are adopted. The principle component analysis (PCA) algorithm
      is introduced in the reconstruction process. It is found that the modulated
      frequency of SI besides the quadratic phases of the imaging system can be easily
      removed with help of PCA. Therefore, phase-shifting is not required both in
      recording and reconstruction process. The simulation is performed to validate our
      method, while the proposed method is applied to the resolution enhancement for
      amplitude-contrast and phase-contrast objects imaging in experiments. The
      resolution is doubled in the simulation, and it shows 78% resolution improvement
      in the experiments.

PMID- 30184857
TI  - Rapid 3D image scanning microscopy with multi-spot excitation and double-helix
      point spread function detection.
AB  - Refocusing after Scanning using Helical phase engineering (RESCH) microscopy has
      previously been demonstrated to provide volumetric information from a single 2D
      scan. However, the practical application of this method is challenging due to its
      limited image acquisition speed and spatial resolution. Here, we report on a
      combination of RESCH and multifocal structured illumination microscopy (MSIM) to
      improve the image acquisition speed and spatial resolution. A phase mask is
      introduced to modulate the conventional point spread function (PSF) to the double
      helix PSF (DH-PSF), which provides volumetric information, and meanwhile, sparse
      multifocal illumination patterns are generated by a digital micromirror device
      (DMD) for parallel 3D subdiffractive imaging information acquisition. We also
      present a strategy for processing the collected raw data with a Richardson-Lucy
      deconvolution and pixel reassignment algorithm to improve the spatial resolution
      of the depth estimation and imaging performance. The proposed 3D image scanning
      microscopy can record 3D specimen information and the corresponding depth
      information from a single multi-spot 2D planar scan, which ensures faster data
      acquisition, larger field of view, and higher spatial resolution than RESCH.
      Finally, we demonstrate the capability of our system with actual experiments.

PMID- 30184858
TI  - Bifacial CdS/CdTe thin-film solar cells with copper nanowires as a transparent
      back contact.
AB  - A bifacial CdS/CdTe thin-film solar cell with a superstrate configuration was
      demonstrated by using copper nanowire (CuNW)/indium tin oxide (ITO) back contacts
      as a transparent and conductive electrode (TCE). CdS and CdTe were deposited by
      chemical bath deposition and close-spaced sublimation techniques, respectively.
      The CuNWs acted both as an acceptor dopant and TCE for the p-CdTe, improving the
      total cell efficiency compared to a copper-free back contact. CuNW/ITO back
      contacts with high optical transmittance (72.3% at 550 nm) and low sheet
      resistance (47.1 Omega/sq.) were obtained. The average cell efficiency of the
      bifacial CdS/CdTe thin-film cells with the optimized CuNW/ITO back contact was
      10.0% (front-side illumination) and 0.55% (rear-side illumination). The quantum
      efficiencies under front-side and rear-side illumination were studied. The
      prepared bifacial cell can facilitate full usage of incoming sunlight (direct or
      diffused), enhancing the output power under cloudy conditions.

PMID- 30184859
TI  - Non-homogeneous composite GMR structure to realize increased filtering range.
AB  - A non-homogeneous composite guided-mode resonant (GMR) filter structure is
      proposed that avoids the multi-mode resonance effect and increases resonant
      wavelength tuning range. The composite filter structure is engineered using a
      combination of a varied-line-spacing (VLS) grating layer with a wedge-shaped
      waveguide layer. The grating is fabricated by holographic interference
      lithography (IL), while the wedge-shaped layer is fabricated using masked ion
      beam etching (MIBE) technology. The resonant wavelength has been observed to vary
      as a function of the spatial position on the structure. In the fabricated
      structure, over a length of 30 mm, the grating period increment is measured to be
      149.2 nm, whereas the increment of the waveguide film thickness is approximately
      100 nm. Experimental results show that a primary reflectance peak is achieved
      spanning a wavelength range of 805.8-1119.0 nm. The device is designed using the
      rigorous coupled-wave analysis (RCWA) method, and the proposed device is toward
      the practical application of GMR filters.

PMID- 30184860
TI  - Simulational and experimental investigation on the actuator-corresponding high
      frequency aberration of the piezoelectric stacked array deformable mirror.
AB  - The high-frequency aberrations (HIFAs) that are corresponding to the actuator
      array have been reported to exist on the initial surface shape of many deformable
      mirrors (DMs), such as the bimorph DM, the unimorph DM, the monomorph DM, and the
      membrane DM. This actuator-corresponding high-frequency aberration (AC-HIFA)
      could not be corrected effectively by the DM and would limit the correction
      ability of the DM. In this paper, we presented the AC-HIFA in a stacked array
      piezoelectric (PZT) DM, which may result in ghost damage that is dangerous in the
      high power laser system. More importantly, we investigated a solution through
      simulation and experiment that by using a mirror plate and a long thin post
      array, which were machined integrally from a piece of BK7 glass, the AC-HIFA
      could be eliminated completely. In addition, the structural parameters'
      influences on the AC-HIFA were investigated in the simulation, which could help
      other researchers to determine appropriate parameters of the mirror and the posts
      and to make a fine surface shape in their own DMs.

PMID- 30184861
TI  - Efficiency enhancement of light color conversion through surface plasmon
      coupling.
AB  - The efficiency enhancement of light color conversion from blue quantum well (QW)
      emission into red quantum dot (QD) emission through surface plasmon (SP) coupling
      by coating CdSe/ZnS QDs on the top of an InGaN/GaN QW light-emitting diode (LED)
      is demonstrated. Ag nanoparticles (NPs) are fabricated within a transparent
      conductive Ga-doped ZnO interlayer to induce localized surface plasmon (LSP)
      resonance for simultaneously coupling with the QWs and QDs. Such a coupling
      process generates three enhancement effects, including QW emission, QD absorption
      at the QW emission wavelength, and QD emission, leading to an overall enhancement
      effect of QD emission intensity. An Ag NP geometry for inducing an LSP resonance
      peak around the middle between the QW and QD emission wavelengths results in the
      optimized condition for maximizing QD emission enhancement. Internal quantum
      efficiency and photoluminescence (PL) decay time measurements are performed to
      show consistent results with LED performance characterizations, even though the
      QD absorption of PL excitation laser may mix with the SP-induced QD absorption
      enhancement effect in PL measurement.

PMID- 30184862
TI  - Ce3+/Mn2+-activated Ca7(PO4)2(SiO4)2: efficient luminescent materials for
      multifunctional applications.
AB  - To develop new efficient phosphors for LEDs based on multifunctional
      applications, a series of Ce3+/Mn2+ activated Ca7(PO4)2(SiO4)2 (CPS) samples were
      prepared by solid-state reaction method. Upon 365 nm excitation, a broad emission
      band around 439 nm in the Ce3+-single-doped CPS was observed. The optimal Ce3+
      concentration was determined to be 3%, for which the quantum efficiency was
      obtained to be 90.4%, higher than that of the commercial BAM phosphor. By
      monitoring 458 nm, an intense and broad excitation band was found from 240 to 400
      nm, which can match well with the near-ultraviolet (NUV) LED chip. For Ce3+-Mn2+
      codoped CPS, a new red emission band belonging to Mn2+ appeared and an energy
      transfer from Ce3+ to Mn2+ was confirmed. It was also found that the emission
      spectra of Ce3+/Mn2+ could well cover the optical absorption bands of plants. The
      fabrication of the phosphors on NUV LED chip indicates that the present phosphors
      could be promising in solid lighting and plants growth.

PMID- 30184863
TI  - Modeling of resonantly pumped mid-infrared Pr3+-doped chalcogenide fiber
      amplifier with different pumping schemes.
AB  - We propose a model for resonantly pumped Pr3+-doped chalcogenide fiber
      amplifiers, which includes excited state absorption and the full spectral
      amplified spontaneous emission spanning from 2 MUm to 6 MUm. Based on this model,
      the observed near- and mid-infrared photoluminescence generated from Pr3+-doped
      chalcogenide fiber is explained. Then the output properties of a 4.1 MUm
      resonantly pumped Pr3+-doped chalcogenide fiber amplifier are simulated in both
      co- and counter-pumping schemes. Results show that the 4.1 MUm counter-pumped
      fiber amplifier can achieve a power conversion efficiency (PCE) of over 62.8% for
      signal wavelengths ranging from 4.5 MUm to 5.3 MUm. This is, to our best
      knowledge, the highest simulated PCE for a Pr3+-doped chalcogenide fiber
      amplifier.

PMID- 30184864
TI  - Fast and robust misalignment correction of Fourier ptychographic microscopy for
      full field of view reconstruction.
AB  - Fourier ptychographic microscopy (FPM) is a newly developed computational imaging
      technique that can provide gigapixel images with both high resolution (HR) and
      wide field of view (FOV). However, there are two possible reasons for position
      misalignment, which induce a degradation of the reconstructed image. The first
      one is the position misalignment of the LED array, which can largely be
      eliminated during the experimental system building process. The more important
      one is the segment-dependent position misalignment. Note that, this segment
      dependent positional misalignment still exists, even after we correct the central
      coordinates of every small segment. In this paper, we carefully analyze this
      segment-dependent misalignment and find that this global shift matters more,
      compared with the rotational misalignments. According to this fact, we propose a
      robust and fast method to correct the two factors of position misalignment of the
      FPM, termed as misalignment correction for the FPM misalignment correction
      (mcFPM). Although different regions in the FOV have different sensitivities to
      the position misalignment, the experimental results show that the mcFPM is robust
      with respect to the elimination of each region. Compared with the state-of-the
      art methods, the mcFPM is much faster.

PMID- 30184865
TI  - Comprehensive analyses of the thermal insensitive noncollinear phase-matching for
      power scalable parametric amplifications.
AB  - Thermal-induced phase-mismatch distortion, which will dramatically deteriorate
      the efficient energy transfer, has become a critical obstacle to power scaling of
      optical parametric amplifiers. To ease this efficiency deterioration, the
      noncollinear optical parametric amplification (OPA) configuration widely employed
      to achieve broadband phase-matching (PM) may also serve as a promising approach
      to optimize the temperature acceptance. In this paper, starting from the
      noncollinear wave-vector equations, a required thermo- and angle-relationship
      analogous to that of noncollinear broadband PM is firstly inferred. Based on the
      presented mathematical criterion, we have explored the potential spectral
      boundaries of this ingenious temperature insensitive OPA scheme. Full-dimensional
      simulations of two types of typical OPA processes were quantitatively discussed.
      Compared with traditional collinear PM designs, the presented noncollinear PM
      configurations show significant common characteristics on improving the
      temperature acceptance and subsequently the overall amplification efficiency. For
      a typical high power parametric process of the 532 nm pumped near-IR OPA at 800
      nm especially, incredible temperature bandwidth exceeding 8000  degrees C was
      obtained while a YCOB (xz plane) crystal is adopted. What is more, it can also be
      applied to ameliorate the gain-spectrum thermo-instability of OPA.

PMID- 30184866
TI  - Coherence-gated photoacoustic remote sensing microscopy.
AB  - Photoacoustic remote sensing microscopy (PARS) represents a new paradigm within
      the optical imaging community by providing high sensitivity (>50 dB in vivo) non
      contact optical absorption contrast in scattering media with a reflection-mode
      configuration. Unlike contact-based photoacoustic modalities which can acquire
      complete A-scans with a single excitation pulse due to slow acoustic propagation
      facilitating the use of time-gated collection of returning acoustic signals, PARS
      provides depth resolution only through optical sectioning. Here we introduce a
      new approach for providing coherence-gated depth-resolved PARS imaging using a
      difference between pulsed-interrogation optical coherence tomography scan-lines
      with and without excitation pulses. Proposed methods are validated using
      simulations which account for pulsed-laser induced initial-pressures and
      accompanying refractive index changes. The changes in refractive index are shown
      to be proportional to optical absorption. It is demonstrated that to achieve
      optimal image quality, several key parameters must be selected including
      interrogation pulse duration and delay. The proposed approach offers the promise
      of non-contact depth-resolved optical absorption contrast at optical-resolution
      scales and may complement the scattering contrast offered by optical coherence
      tomography.

PMID- 30184867
TI  - Transitional Goos-Hanchen effect due to the topological phase transitions.
AB  - We examine the Goos-Hanchen (GH) effect for a Gaussian beam impinging on the
      surface of silicene whose topological phase transitions can be modulated by
      external electric field and/or irradiating circular polarized light. It is shown
      that both the spatial and angular shifts in GH effect present a sharp jump due to
      the topological phase transitions. The transitional GH effect can be attributed
      to transitional optical conductivity, which relates to Berry curvature and Chern
      numbers. These results can be extensively extended to other two-dimensional
      atomic crystals in graphene family. We believe that the transitional GH effect
      may offer a possible way to determine the Berry curvature, Chern numbers, and
      topological phase transition by a direct optical measurement.

PMID- 30184868
TI  - Enhanced phase-sensitive OTDR system with pulse width modulation Brillouin
      amplification.
AB  - A pulse width modulation (PWM) Brillouin amplification has been proposed and
      demonstrated to improve the signal-to-noise ratio (SNR) and sensitivity of phase
      sensitive optical time domain reflectometry (F-OTDR) especially for the far end
      of a sensing fiber. In the logarithmic unit, arbitrary gain distribution can be
      realized with the customizable PWM function. The gain distribution is adjustable
      by tuning the PWM parameters. To prove the concept, three typical gain
      distributions including up-ramp sawtooth, sine and triangle have been achieved
      with the corresponding driving functions. In experiments, a linear PWM pump light
      has been used to amplify the backscattering Rayleigh light. The signal at the
      leading end has been enhanced by about 11.5 dB. Meanwhile, 9 dB transmission
      attenuation (along 25 km SMF) has also been compensated excellently. To verify
      the effectiveness of attenuation compensation, two vibrations with a frequency of
      100 Hz and 300 Hz have been recovered accurately at the trailing end. Besides,
      preamplifier and acoustic-optic modulator (AOM) was used to suppress the ASE
      noise and further improve the effective ER, respectively. With that, lower
      relative intensity noise (RIN) has been obtained in the proposed system compared
      to the conventional Brillouin amplification in F-OTDR. So the proposed PWM
      Brillouin amplification not only improves the SNR but also equalizes the
      sensitivity along whole sensing fiber. It avoids the complex calibration and
      suppresses the false alarm rate in field application. Foreseeably, this scheme is
      universal and can be adopted by other distributed fiber optic technique to
      enhance the system performance.

PMID- 30184869
TI  - Bonded thin film lithium niobate modulator on a silicon photonics platform
      exceeding 100 GHz 3-dB electrical modulation bandwidth.
AB  - We demonstrate an ultra-high-bandwidth Mach-Zehnder electro-optic modulator
      (EOM), based on foundry-fabricated silicon (Si) photonics, made using
      conventional lithography and wafer-scale fabrication, oxide-bonded at 200C to a
      lithium niobate (LN) thin film. Our design integrates silicon photonics light
      input/output and optical components, such as directional couplers and low-radius
      bends. No etching or patterning of the thin film LN is required. This hybrid Si
      LN MZM achieves beyond 106 GHz 3-dB electrical modulation bandwidth, the highest
      of any silicon photonic or lithium niobate (phase) modulator.

PMID- 30184870
TI  - Dynamics of Gaussian beam modeled by fractional Schrodinger equation with a
      variable coefficient.
AB  - In the paper, we investigate the propagation dynamics of the Gaussian beam
      modeled by the fractional Schrodinger equation (FSE) with a variable coefficient.
      In the absence of the beam's chirp, for smaller Levy index, the Gaussian beam
      firstly splits into two beams, however under the action of the longitudinal
      periodic modulation, they exhibit a periodically oscillating behaviour. And with
      the increasing of the Levy index, the splitting behaviour gradually diminishes.
      Until the Levy index equals to 2, the splitting behaviour is completely replaced
      by a periodic diffraction behaviour. In the presence of the beam's chirp, one of
      the splitting beams is gradually suppressed with the increasing of the chirp,
      while another beam on the opposite direction becomes stronger and exhibits a
      periodically oscillating behaviour. Also, the oscillating amplitude and period
      are investigated and the results show that the former is dependent on the
      modulation frequency, the Levy index and the beam's chirp, the latter depends
      only on the modulation frequency. Thus, the evolution of the Gaussian beam can be
      well manipulated to achieve the beam management in the framework of the FSE by
      controlling the system parameters and the chirp parameter.

PMID- 30184871
TI  - Hybrid micro-optical elements by laser-based fabrication of Fresnel lenses on the
      end face of gradient index lenses.
AB  - Fresnel lenses are fabricated directly upon the end face of gradient index (GRIN)
      lenses by F2-laser machining at 157 nm wavelength. The employed laser processing
      technique combines a mask projection configuration at 25-x demagnification with a
      rotation of the structured lens. The ablation characteristics of the GRIN
      materials require very high pulse fluences with typical values above 7 J/cm2.
      Topography measurements on the Fresnel lenses reveal a good contour accuracy with
      residual deviations from the design profile well below 100 nm. Such hybrid
      optical elements, combining GRIN lenses with diffractive lenses in one element,
      can serve as the basis for high-performance micro-optical imaging systems with
      diameters up to 2 mm. Examples of possible applications include imaging sensors
      like proximity sensors or color-corrected microscope objectives with high
      numerical aperture for endoscopy applications.

PMID- 30184872
TI  - Polarization-selective dual-wavelength gap-surface plasmon metasurfaces.
AB  - In this paper, we present a general method to realize polarization-selective dual
      wavelength gap-surface plasmon metasurfaces (GSPMs), which are composed of
      strongly anisotropic meta-atoms periodically arranged in a rectangular lattice
      with two degrees of freedom to independently control the reflection phase and
      amplitude of orthogonal linear polarizations at two discrete wavelengths. We
      design and demonstrate dual-wavelength GSPMs as polarization beam splitters and
      focusing metamirrors operating at 850 and 1550 nm simultaneously. Our work
      provides a general approach to design multiwavelength, multifunctional
      metasurfaces with various potential applications.

PMID- 30184873
TI  - Two-dimensional vector bending sensor based on seven-core fiber Bragg gratings.
AB  - We demonstrated a two-dimensional vector-bending sensor by use of fiber Bragg
      gratings (FBGs) inscribed in a homogeneous seven-core fiber. Seven FBGs were
      simultaneously inscribed in each of all seven cores using a modified Talbot
      interferometer and a lens scanning method. The vector bending response of six
      outer-core FBGs was investigated at all 360 degrees  directions with a step size
      of 15 degrees . The bending sensitivities of the six outer-core FBGs display six
      perfect '8'-shaped patterns in a polar-coordinate system. That is, they exhibit
      strong bending-direction dependence with a maximum sensitivity of 59.47 pm/m-1.
      The orientation and amplitude of the vector bending can be reconstructed using
      measured Bragg wavelength shifts of any two off-diagonal outer-core FBGs. So, the
      six outer-core FBGs have 12 combinations for bend reconstruction, which can be
      averaged across multiple reconstructions to develop an accurate two-dimensional
      vector bending sensor. The average relative error was lower than 4.5% for
      reconstructed amplitude and less than 2.8% for reconstructed orientation angle
      theta. Moreover, the seven-core FBGs offer several advantages such as a compact
      structure, fabrication flexibility, and the temperature compensating ability of
      central-core FBG.

PMID- 30184874
TI  - Region-adaptive path planning for precision optical polishing with industrial
      robots.
AB  - In the field of ultra-precision manufacturing, industrial robotic polishing has
      the potential to become a more economical and intelligent method than the
      conventional polishing machines. But the challenge of the robotic polishing lies
      in the low control accuracy, which seriously affects the polishing quality. In
      this paper a new region-adaptive path planning method is proposed, where the path
      is generated adaptively according to the specific form error. Each time only the
      regions with form error large enough are processed, thereby improving the
      polishing stability and efficiency. Smooth paths are generated based on the
      hexagonal meshing of the processing regions to avoid sharp turning, and then the
      dwell time is calculated by space-variant deconvolution. The PVr metric of the
      final form error resulting from the robotic polisher converges down to lambda/15.
      In addition this method can reduce the polishing time by 80%, henceforth the
      stability and efficiency of robotic polishing can be greatly improved.

PMID- 30184875
TI  - Enhanced direct-gap light emission from Si-capped n+-Ge epitaxial layers on Si
      after post-growth rapid cyclic annealing: impact of non-radiative interface
      recombination toward Ge/Si double heterostructure lasers: erratum.
AB  - We report an error in Fig. 13(a) of our article [Opt. Express25, 21286 (2017)],
      and the correction is presented. Typographical errors in the text are also
      corrected.

PMID- 30184876
TI  - All-in-fiber SESAM based comb oscillator with an intra-cavity electro-optic
      modulator for coherent high bandwidth stabilization.
AB  - We demonstrate the stabilization of an all-in-fiber polarization maintaining semi
      conductor saturable absorber mirror (SESAM) mode locked frequency comb oscillator
      with an intra-cavity waveguide electro-optic phase modulator (EOM) to a narrow
      linewidth HeNe laser over 46 hours. The high feedback bandwidth of the EOM allows
      a coherent optical lock with an in-loop integrated phase noise of 1.12 rad
      (integrated from 10 Hz to 3 MHz) from the carrier signal. No piezo fiber
      stretcher was required to guarantee long-term stabilization, preventing
      mechanical degradation of the optical fibers and enabling a long lifetime of the
      oscillator. As an application a hybrid stabilization scheme is presented, where a
      comb tooth is phase locked to a longitudinal mode of the large ring laser "G"
      located at the Geodatic Observatory Wettzell. The hybrid stabilization scheme
      describes the optical lock of the frequency comb to the G laser and the
      simultaneous compensation of the ring laser frequency drift by comparing the comb
      repetition rate against an active H-maser reference. In this context the ring
      laser reached a fractional Allan deviation of 5 . 10-16 at an integration time of
      16384 s.

PMID- 30184877
TI  - On channel estimation schemes for APD-based DDM-OFDM-PONs under sub-Nyquist
      sampling.
AB  - Implementing preprocessing in a delay-division multiplexing (DDM) orthogonal
      frequency-division multiplexing (OFDM) passive optical network (PON) requires a
      priori knowledge of channel responses, which need to be estimated under the
      constraint of sub-Nyquist analog-to-digital sampling. The localized approach
      allocates subcarriers in different frequency zones to training symbols in
      different time slots for channel estimation without spectral overlap.
      Unfortunately, the localized scheme is susceptible to inaccurate estimation when
      using an avalanche photodiode (APD), due to variations in APD saturation
      associated with different training symbols. Instead of localizing all subcarriers
      of a training symbol in a single frequency zone, we propose distributing training
      subcarriers through various frequency zones. This distributed scheme would
      prevent spectral overlap and also reduce the degree of variation in APD
      saturation, thereby improving the accuracy of channel estimation. Alternatively,
      we propose an orthogonal scheme in which each training symbol uses all of the
      subcarriers simultaneously. The orthogonality specified among consecutive
      training symbols should make it possible to estimate the channel response with
      low computational complexity. We conducted experiments to compare various schemes
      used for channel estimation in a 25-Gbps APD-based OFDM-PON. Our results revealed
      that the orthogonal scheme achieved the best results, and the localized scheme
      provided the worst channel estimates. We demonstrate the application of the
      orthogonal scheme in a penalty-free DDM system at 1/32 of the Nyquist rate, which
      provided a loss budget of 28 dB after fiber transmission over a distance of 25
      km.

PMID- 30184878
TI  - Performance of M-PAM FSO communication systems in atmospheric turbulence based on
      APD detector.
AB  - We characterize the performance of the optical signal propagation model of multi
      level pulse amplitude modulation (M-PAM) based on avalanche photodiode (APD)
      detector in the free-space link for the first time. When the number of photons
      absorbed by the active surface of the APD is large enough, the bit error rate
      (BER) performance relationship of the systems based on the signal intensity and
      the photon characteristics are depicted. We use the Gamma-Gamma (G-G) channel
      model to analysis the communication systems with joint parameter constraints, and
      demonstrate the atmospheric turbulence intensity, link lengths, optical
      wavelength, symbol transmission rate, temperature of APD and pointing errors
      (PEs) impact on the system average bit error rate (ABER) performance. Moreover,
      the relationship between signal-to-noise-ratio (SNR) and ABER rate is given. The
      numerical results show that the 4-PAM free-space optical (FSO) communication is
      suitable for medium-to-weak turbulence, and the high gain of APD can mitigate the
      influence of ABER. The best detection condition of the 4-PAM optical signal is at
      least 20 dB SNR, when the ABER is under the 7% forward error correction (FEC)
      limit of 3.8 * 10-3. This work provides a reference for parameter designing and
      evaluating in M-PAM FSO communication systems.

PMID- 30184879
TI  - Heterogeneous and cross-distributed metal structure hybridized with MoS2 as high
      performance flexible SERS substrate.
AB  - The heterogeneous metal nanostructures have attracted great interest in various
      applications due to the synergistic effects between two noble metals, especially
      in surface enhanced Raman scattering (SERS) region. Herein, we prepared a 3D SERS
      active substrate based on heterogeneous and cross-distributed metal structure
      hybridized with MoS2by in situ synthesizing gold nanoparticles (AuNPs) on MoS2
      membrane. The AuNPs-AgNPs/MoS2/P-Si hybrid SERS substrate were characterized by a
      scanning electron microscope (SEM), a transmission electron microscope (TEM) and
      X-ray photoelectron spectroscopy (XPS) to investigate the character and the
      content of elements. In virtue of the heterogeneous and cross-distributed
      structure and ultra-narrow interparticle gap generating strong electric fields
      enhancement, the ultra-low concentration of probe molecule were detected (the LOD
      of 10-12 M for R6G and CV, 10-11 M for MG), serving the optimal SERS performance.
      The excellent uniformity and reproducibility were achieved by the proposed
      substrate. Moreover, the flexible MoS2/AuNPs-AgNPs/PMMA pyramidal SERS substrate
      was applied to detect melamine molecule in liquid milk (the LOD reached 10-9 M),
      which revealed great potential to be an outstanding SERS substrate for biological
      and chemical detection.

PMID- 30184880
TI  - Method for direct observation of Bloch oscillations in semiconductors.
AB  - We propose a scheme for real-time observations of Bloch oscillations in
      semiconductors using time-resolved band gap emission spectroscopy. By solving the
      time-dependent Schrodinger equation, we find one remarkable band gap emission
      besides the normal high harmonics generated in the interaction of a mid-infrared
      laser pulse and a semiconductor. It is shown that the band gap emission yield is
      directly connected to the population in the conduction band (CB). By adopting a
      pump-probe scheme, the time-dependent population in the CB, that is the dynamical
      Bloch oscillation, can be probed by measuring the band gap emission signal versus
      pump-probe delay. We also present a model based on accelerated Bloch states to
      explain the time-resolved measurement of dynamical Bloch oscillation.

PMID- 30184881
TI  - Plasmon-phonon-polariton modes and field enhancement in graphene-coated hexagon
      boron nitride nanowire pairs.
AB  - Both plasmon-phonon-polariton (SPP-PHP) modes and phonon-polariton (PHP) modes
      supported in graphene-coated hexagon boron nitride (h-BN) single nanowire are
      presented. The field distributions of the lowest 5 order modes of SPP-PHP modes
      supported in graphene-coated hexagon boron nitride nanowire pairs (SPP-PHP-GHNP)
      and the lowest 5 order modes of PHP modes supported in graphene-coated hexagon
      boron nitride nanowire pairs (GHNP) are also demonstrated and analyzed,
      respectively. The results of numerical calculation show that SPP-PHP-GHNP mode 0
      owns the strongest confinement and lowest loss among the lowest 5 order modes of
      SPP-PHP-GHNP. Furthermore, the field enhancement of SPP-PHP-GHNP mode 0 can reach
      over 105 by controlling the geometry parameters of GHNP. Meanwhile, the influence
      of tuning the Fermi level of graphene on the field enhancement is also presented
      in the paper. The proposed structure may improve the development of graphene-h-BN
      based optoelectronic devices.

PMID- 30184882
TI  - Miniature fiber-optic Fabry-Perot refractive index sensor for gas sensing with a
      resolution of 5x10-9 RIU.
AB  - This paper presents a micro-machined, high-resolution refractive index sensor
      suitable for monitoring of small changes in the composition of gases.
      Experimentally demonstrated measurement resolution, induced by gas composition
      variation, proved to be in the range of 5x10-9 of a Refractive Index Unit (RIU).
      The proposed all-silica, all-fiber sensor consists of an open-path Fabry-Perot
      micro-cavity that includes an in-fiber collimation and temperature-sensing
      segment. It is shown that a sensor's resolution depends strongly on the signal
      interrogator's properties and that, for a given interrogator, there is an optimum
      Fabry-Perot cavity length that yields the highest system resolution. Furthermore,
      high-resolution pressure and in situ temperature compositions of measurement
      results are required to obtain an unambiguous correlation between the gas
      composition and measured Refractive Index within the presented resolution range.

PMID- 30184883
TI  - Soil directioal (biconical) reflectance in the principal plane with varied
      illumination angle under dry and saturated conditions.
AB  - Change in directional (biconical) spectral reflectance was monitored for three
      soil samples under air dry and saturated conditions in the laboratory. The
      illumination angle was set consecutively at thetai  = -10 degrees , -40 degrees ,
      and -70 degrees  (left side of the sample on the principal plane), while the
      observation angle ranged from thetao  = -60 degrees  to + 60 degrees  (both sides
      of the sample in the principal plane) in 5 degrees  increments. The soil samples
      were chosen to represent a variety of soil properties. Emphasis is on
      observations that illustrate the changes in the directional and spectral
      distribution of soil reflectance when the soil is dry or saturated.

PMID- 30184884
TI  - Spin photonic forces in non-reciprocal waveguides.
AB  - Optical forces acting on particles - controlled by the intensity, polarization
      and direction of optical beams - have become an important tool in manipulation,
      sorting and analysis of nano/micro-particles. The nature of these forces has been
      well understood in reciprocal structures exhibiting time-reversal symmetries.
      Here, we investigate the nature of optical forces in non-reciprocal structures
      with non-degenerate counter-propagating modes. We consider the specific case of
      non-reciprocity induced via translational motion and show that the two counter
      propagating modes in a moving slab-waveguide are not degenerate which results in
      a non-zero lateral and longitudinal force on a nanoparticle. We prove that these
      anomalous forces are fundamentally connected to near-field photonic spin in
      optical waveguides and explain their directionality using universal spin-momentum
      locking of evanescent waves. The presented results show that the interplay of
      photon spin and non-reciprocity can lead to unique avenues of controlling
      nanoscale optical forces on-chip.

PMID- 30184886
TI  - Reconfigurable all-dielectric antenna-based metasurface driven by multipolar
      resonances.
AB  - Dielectric nanoantenna-based metasurfaces have attracted wide attention for their
      outstanding performance in light manipulation with low loss and full phase
      coverage enabled by multipolar resonances. To make the metasurfaces actively
      tunable, we adopt a kind of phase-changing material Ge2Sb2Te5 to construct non
      volatile, switchable antenna-based metasurfaces in the mid-infrared spectrum
      region. Our design of the metasurface can realize switching between electric and
      magnetic dipole resonances across a broad spectrum region through crystalline
      amorphous phase transitions under fixed design. Moreover, the transmission
      switching contrast between different phases can be up to 30dB (-30dB), due to the
      shift of multipolar resonances. This reconfigurable antenna-based metasurface
      will pave the way for ultimate design of light modulators, deflectors, holograms
      and so on for future optical communication networks.

PMID- 30184885
TI  - Bismuth-doped fiber laser at 1.32 MUm mode-locked by single-walled carbon
      nanotubes.
AB  - Bismuth-doped fiber is a promising active media for pulsed lasers operating in
      various spectral regions. In this paper, we report on a picosecond mode-locked
      laser at a wavelength of 1.32 MUm, based on a phosphosilicate fiber doped with
      bismuth. Stable self-starting generation of dissipative solitons, using single
      walled carbon nanotubes (SWCNT) as a saturable absorber, was achieved. Evolution
      of the pulsed regime, depending on pump power, and stability of the pulsing were
      investigated.

PMID- 30184887
TI  - Chirp-adjustable square-wave pulse in a passively mode-locked fiber laser.
AB  - A passively mode-locked fiber laser to generate chirp-adjustable square-wave
      pulses is reported. A simple chirp measurement system is designed to study the
      output chirp of the fiber laser. The results indicate that the chirp of the
      square-wave pulses in our fiber laser can be adjusted by the polarization
      controllers inside the cavity. Three typical chirp states, including random
      chirp, V-shaped chirp and linear chirp, are achieved. This kind of fiber laser
      cannot only help to further understand the characteristics of square-wave pulse
      but also serve as multifunction light source for potential applications.

PMID- 30184888
TI  - Redistributing the energy flow of a tightly focused radially polarized optical
      field by designing phase masks.
AB  - Redistributing the transverse energy flow in the focal plane of a tightly focused
      radially polarized optical field is described. We develop from theory a
      generalized analytical model for calculating the distributions of the
      electromagnetic field and the Poynting vector for a tightly focused radially
      polarized laser beam superposed with an optical vortex. We further explore the
      redistribution of the energy flow by designing phase masks, including traditional
      and annular vortex phase masks. Flexible control of the transverse energy flow
      rings is obtained with these phase masks. They provide a simple solution to
      transport absorptive particles along certain paths and therefore might be help in
      optical tweezer manipulations.

PMID- 30184889
TI  - Nonlinearity compensation using optical phase conjugation deployed in discretely
      amplified transmission systems.
AB  - We introduce a closed form equation, validated by simulations and experimental
      results that predicts the residual nonlinear noise ratio in mid-link OPC assisted
      discretely amplified systems. The model anticipates the reduction in performance
      enhancement achieved by mid-link OPC as the bandwidth of the modulated signals
      increases. The numerical analysis shows that uncompensated signal-signal
      interactions limit the performance improvement achieved by the introduction of
      additional OPCs. The numerical analysis predicts that the deployment of shorter
      amplifier spacing will lead to a greater performance enhancement. The numerical
      results are validated by experimentally testing of 2x, 4x, and 8x28Gbaud PM-QPSK
      systems with mid-link OPC compensation in a discretely amplified system with
      100km amplifier spacing. The experimentally obtained reach enhancement (43%, 32%,
      and 24% for 2x28Gbaud, 4x28Gbaud, and 8x28Gbaud, respectively) confirms that the
      compensation efficiency of mid-link OPC is highly dependent on the number of
      channels (bandwidth) propagating along the system.

PMID- 30184890
TI  - Experimental demonstration of 72% reach enhancement of 3.6Tbps optical
      transmission system using mid-link optical phase conjugation.
AB  - We experimentally demonstrate nonlinear noise compensation in an optical phase
      conjugation assisted 1st order Raman amplified 30x30Gbaud DP-QPSK transmission
      system with a spectral efficiency of 3.6b/s/Hz. We show that by optimizing the
      link symmetry, even with only 1st order Raman amplification a single, mid-link,
      optical phase conjugation compensates for 90% of the signal-signal nonlinear
      interference resulting in a 2.3dB performance enhancement. We show that
      increasing the number of optical phase conjugations in the presence of 10%
      residual nonlinearity results in a reduction in the performance enhancement owing
      to an enhancement in the nonlinear noise generation efficiency of the system. We
      achieve a record 72% optical phase conjugation enabled reach enhancement of the
      30x30Gbaud DP-QPSK signals.

PMID- 30184891
TI  - 100 Gb/s PAM4 transmission system for datacenter interconnects using a SiP ME-MZM
      based DAC-less transmitter and a VSB self-coherent receiver.
AB  - We experimentally demonstrate a digital-to-analog-converter-less (DAC-less)
      vestigial sideband (VSB) 4-level pulse amplitude modulation (PAM4) transmission
      system for data center interconnects (DCIs) using a silicon photonic (SiP) multi
      electrode Mach-Zehnder modulator (ME-MZM) based DAC-less transmitter and a VSB
      self-coherent receiver. The impacts of linear and nonlinear impairments on the
      proposed system and their mitigation methods are comprehensively studied. By
      using Kramer-Kronig (KK) detection, frequency domain chromatic dispersion
      compensation, and short-memory time domain Volterra equalization at the receiver,
      we report a 112 Gb/s PAM4 transmission over 40 km standard single mode fiber
      (SSMF) with a bit error rate (BER) below the 7% overhead (OH) hard-decision
      forward error correction threshold of 3.8 * 10-3, and a 120 Gb/s PAM4
      transmission over 80 km SSMF with a BER below the 20% OH soft-decision forward
      error correction threshold of 2 * 10-2, without any transmitter side digital
      signal processing such as pre-emphasis and pulse shaping.

PMID- 30184892
TI  - Infrared simulation of large-scale urban scene through LOD.
AB  - The growing use of infrared (IR) imaging systems places increasing demands for
      simulating infrared images of real scenes. Utilizing images captured from
      unmanned aerial vehicles (UAV), we propose a semi-automatic pipeline to generate
      large-scale IR urban scenes in the form of levels of detail (LODs). It
      significantly reduces the cost of labor and time while providing detailed IR
      structures. Starting from the surface meshes generated by multi-view stereo (MVS)
      systems, we produce watertight LODs via semantic segmentation and structure-aware
      approximation. For each LOD, we divide the surfaces into triangle facets of
      specific scales. For each facet, one material attribute is attached, and the heat
      balance equations are solved to obtain the temperature. Three strategies are
      proposed to accelerate the thermal distribution calculation. Finally, by
      synthesizing the radiance distribution, the whole IR scenes are generated and
      rendered. Experiments on real urban scenes show that the proposed pipeline could
      effectively simulate IR scenes of large-scale urban scenes.

PMID- 30184893
TI  - Frequency comb generation in a resonantly pumped exciton-polariton microring
      resonator.
AB  - We develop a scheme for generation of a regular sequence of narrow spectral lines
      (optical frequency comb) in semiconductor micro-ring resonators operating in the
      strong-coupling regime. A strong optical nonlinearity of exciton-polaritons,
      forming as mixed states between the microcavity photons and quantum-well
      excitons, allows for a low-threshold operation. This work demonstrates visibility
      of using the exciton-polaritons for the purposes of generation of GHz combs and
      trains of picoseconds pulses for future all-polariton information processing
      schemes.

PMID- 30184894
TI  - Optimization strategies for modulation transfer spectroscopy applied to laser
      stabilization.
AB  - We present a general analysis for determining the optimal modulation parameters
      for the modulation transfer spectroscopy scheme. The results are universally
      valid and can be applied to spectroscopy of any atomic species requiring only the
      knowledge of the effective linewidth Gammaeff. A signal with optimized slope and
      amplitude is predicted for a large modulation index M and a modulation frequency
      comparable to the natural linewidth of the spectroscopic transition. As a result
      of competing practical considerations, a modulation index in the range of 3 <= M
      <= 10 has been identified as optimal. This parameter regime is experimentally
      accessible with a setup based on an acousto-optic modulator. An optimized signal
      for spectroscopy of the rubidium D2 line is presented. The signal shape and the
      dependence on the modulation parameters are in very good agreement with the
      theoretical description given. An experimental procedure for achieving a strong
      suppression of residual amplitude modulation is presented. Based on the optimized
      signal, we demonstrate long-term laser stabilization resulting in a laser
      linewidth of 150 kHz (16 s average) and a frequency stability of 18 kHz (rms)
      over 15 hours.

PMID- 30184895
TI  - Integrating fluorescence computed tomography with optical sheet illumination for
      imaging of live single cells.
AB  - We present a new approach for three-dimensional (3D) live single-cell imaging
      with isotropic sub-micron spatial resolution using fluorescence computed
      tomography (fCT). A thin, highly inclined and laminated optical (HILO) sheet of
      light is used for fluorescence excitation in live single cells that are rotated
      around an axis perpendicular to the optical axis. During a full rotation, 400-500
      two-dimensional (2D) projection images of the cell are acquired from multiple
      viewing perspectives by rapidly scanning the HILO light sheet along the optical
      axis. We report technical characteristics of the HILO approach and the results of
      a quantitative comparison with conventional epi fCT, demonstrating that HILO fCT
      offers significantly (about 17 times) reduced photobleaching and a two-fold
      improvement in 3D imaging contrast. We discuss potential application areas of the
      method for cell structure studies in live single cells with isotropic 3D spatial
      resolution.

PMID- 30184896
TI  - Ultra-broadband, polarization-independent, wide-angle absorption in impedance
      matched metamaterials with anti-reflective moth-eye surfaces.
AB  - We computationally study periodic impedance-matched metal-dielectric
      metamaterials and the advantage of imprinting moth-eye surfaces on them.
      Impedance-matched metamaterials are known to act as strong, polarization
      independent, broadband absorbers. However, in the infrared region far from the
      metal's plasma frequency, the reflection from metal layers dominates over the
      absorption. Using anti-reflective moth-eye surfaces we show that it is possible
      to obtain absorption independent of polarization or incidence angle, over an
      exceptionally broad frequency range from 400 nm to 6 MUm.

PMID- 30184897
TI  - Long distance crosstalk-supported transmission using homogeneous multicore fibers
      and SDM-MIMO demultiplexing.
AB  - We propose and evaluate the use of spatial-division multiplexing (SDM) multiple
      input multiple output (MIMO) systems to support long distance transmission using
      single-mode homogeneous multicore fibers. We show that on a uniform link with per
      span inter-core skew compensation, the required SDM-MIMO memory length
      corresponds to the largest inter-core skew per span on the link. Furthermore, we
      show that with inter-core skew compensation, the required memory length of the
      SDM-MIMO is nearly constant with the transmission distance for accumulated
      crosstalk below -11 dB. We experimentally demonstrate the use of SDM-MIMO with a
      memory length of 20 ns on a long distance transmission link using 20 GBaud PDM
      QPSK signals. We achieve a reach of 9780 km, which corresponds to a 9%
      improvement over the case without SDM-MIMO. We also show that the use of SDM-MIMO
      is applicable to the transmission of signals with higher modulation order,
      achieving transmission reach improvements of 14% for 20 GBaud PDM-16QAM and PDM
      64QAM signals.

PMID- 30184898
TI  - Fano signatures between intersubband and ponderomotive responses in MQW
      structures.
AB  - We present an in-depth theoretical and numerical discussion on the Fano
      signatures observed in differential transmission spectra obtained from
      multiquantum well structures. These signatures stem from ponderomotive and
      intersubband polarization currents modified by the coupling between the optical
      responses of different layers. A detailed discussion of this process is provided,
      evaluating quantitatively the amplitude and shape of the Fano signatures and
      their dependence on structural parameters, such as carrier concentration and
      layer width. The theoretical model described here aims to predict quantitatively
      the weight of the contributions of the ponderomotive currents in relation to the
      intersubband ones. In order to include the effect of the entire structure in the
      theoretical spectra, the optical response of each layer is addressed within the
      density matrix formalism and encompassed in an optical transfer matrix. This
      method also ensures the correct inclusion of the phase sensitive superposition of
      optical responses of different layers on which the Fano signatures are based.
      Numerical simulations obtained from the presented theoretical approach are in
      excellent agreement with the behavior observed in previous experiments.

PMID- 30184899
TI  - 100 Gbit/s PAM4 signal transmission and reception for 2-km interconnect with
      adaptive notch filter for narrowband interference.
AB  - In this paper, we experimentally demonstrate the transmission of 56 Gbaud four
      level pulse amplitude modulation (PAM4) signal over 2-km single mode fiber (SMF)
      with intensity modulation and direct detection (IM/DD) scheme, while the bit
      error-ratio (BER) of the PAM4 signal is under hard-decision forward error
      correction (HD-FEC) threshold of 3.8 * 10-3. Linear pre-equalization is
      implemented in the transmitter side with a 3-tap finite-impulse-response (FIR)
      filter to compensate for the intersymbol interference (ISI) induced by system
      bandwidth limitation. Receiver side equalization is realized with training
      sequence (TS) based feed-forward equalizer (FFE) with decision-feedback equalizer
      (DFE). Furthermore, an Adaptive Notch Filter (ANF) is proposed to suppress the
      digital-to-analog converter (DAC) clock leakage induced narrowband interference
      for the first time, and the bandwidth of the ANF is optimized to achieve the best
      BER performance.

PMID- 30184900
TI  - Non-iterative dartboard phase filter for achieving multifocal arrays by
      cylindrical vector beams.
AB  - We proposed an analytically designed non-iterative dartboard phase filter (DPF)
      to achieve multifocal arrays by cylindrical vector beams. The DPF is composed of
      sectors, which is two-dimensionally divided in polar coordinates, along the
      radial and azimuthal directions. Meanwhile, a modulation factor was first
      proposed and introduced into the DPF to improve the intensity uniformity of the
      generated multifocal array. By the proposed DPF, the one-dimensional, two
      dimensional and three-dimensional multifocal arrays are generated, which have
      intensity uniformities larger than 92.5%. The focal position and polarization of
      these generated multifocal arrays can be controlled, while the transverse sizes
      of each focal spot are subwavelength. The proposed DPF and the generated
      multifocal arrays have potential applications in the fields of polarization
      multiplexed data storage, polarization-sensitive nanophotonic devices and
      parallel direct laser writing.

PMID- 30184901
TI  - Inscription of silicon waveguides using picosecond pulses.
AB  - Direct writing of single-mode waveguides into crystalline silicon using ps laser
      pulses is presented. The embedded structures were fabricated by moving the focal
      position along the beam axis with the help of a long distance microscope
      objective. In situ monitoring during inscription was performed to analyze the
      processing dynamics. The waveguide generation is based on pronounced multi-pulse
      interaction at moderate pulse energies around 100 nJ. All samples were
      characterized in terms of mode field distribution and damping losses.
      Calculations indicate an induced refractive index change in the range of 10-3 to
      10-2. Moreover, a Y-splitter was realized to demonstrate the potential of this
      process.

PMID- 30184902
TI  - Adaptive space-time compression for efficient massive MIMO fronthauling.
AB  - One of the key features of the forthcoming fifth-generation (5G) communications
      is the deployment of massive multiple-input-multiple-output (MIMO) antennas to
      support ultra-high mobile traffic density. This scenario will pose a serious
      challenge on the capacity of mobile fronthaul in the centralized/cloud radio
      access network (C-RAN) since the required fronthaul bandwidth would linearly
      increase with number of antennas if conventional fronthaul interfaces (e.g.,
      CPRI) are used. In this paper, we propose an adaptive space-time compression
      technique to significantly improve bandwidth efficiency of fronthaul. The
      technique incorporates an adaptive spatial filter to track the signal subspace
      and reduce the number of spatial channels, followed by adaptive quantizers to
      compress bandwidth of each channel in time domain. Enabled by the technique, the
      required fronthaul bandwidth becomes only dependent on the number of users, which
      is no longer proportional to the number of antennas. Moreover, compared with
      traditional fronthaul compression schemes in only the time domain, the
      flexibility of the compressor increases, and joint space-time optimization
      becomes feasible. On the other hand, optical fronthaul bandwidth is usually
      limited by cost-effective optical and electronic components. Moreover, increased
      reach would limit the bandwidth of IM-DD-based fronthaul (due to chromatic
      dispersion) as well as the received optical power. We experimentally investigate
      the combined optimization of a proposed space-time compressor with an optical
      fronthaul link. Experimental results of uplink 256-antenna fronthaul (259.5-Gb/s
      CPRI-equivalent rate) show that 32 users with 20MHz (30.72MSa/s) OFDM signal with
      lower-than-1% EVM are supported by 10GBd PAM4 optical interface.

PMID- 30184903
TI  - Residual-stress-induced helical long period fiber gratings for sensing
      applications.
AB  - We demonstrate a high-efficiency grating fabrication system, which can be used to
      inscribe a high-quality helical long period fiber grating (HLPFG) on single-mode
      fiber by means of hydrogen-oxygen flame. Such the HLPFG can be produced in
      enormous quantities with a uniform grating parameters and good reproducibility of
      grating inscription. Possible mechanisms for refractive index modulation in the
      HLPFG can be attributed to residual stress concentration by solidifying the
      periodic twisting stress under a fused status of optical fiber. Moreover, the
      HLPFG exhibits an excellence performance of high temperature sensing with a high
      sensitivity of ~132.8 pm/ degrees C and a measuring range from room temperature
      to 900  degrees C. Comparing to the traditional LPFG fabricated by CO2 laser or
      arc discharge technique, the HLPFG has a low the bending and tensile strain
      sensitivity of 1.94 nm/(1/m) and 1.41 pm/MUepsilon, respectively. So the proposed
      HLPFG could have a great potential in special applications as optical high
      temperature sensors.

PMID- 30184904
TI  - Time, space, and spectral multiplexing for radiation balanced operation of
      semiconductor lasers.
AB  - Radiation balanced lasing (RBL) is an attractive pathway towards the development
      of high power and good beam quality lasers because heat removal via anti-Stokes
      luminescence (optical refrigeration) does not require additional connections and
      components and the heat is dissipated away from the active medium. Optical
      refrigeration had been demonstrated in the rare-earth doped laser medium but is
      far more difficult to achieve it in semiconductors laser medium. The main
      obstacle to achieve RBL in semiconductors is that the most efficient cooling
      occurs at relatively low carrier densities, while the gain required to sustain
      laser operation occurs at much higher densities. In this study, we explore the
      means of resolving this conundrum by separating the optical refrigeration and
      lasing in temporal, spatial, and/or spectral domains. Time multiplexing involves
      modulating the pump and operating the laser in pulse modes with lasing and
      cooling intervals. Space multiplexing involves having separate regions (quantum
      wells and dots) for lasing and cooling. The spectral multiplexing involves
      operating with two separate pumps - one for lasing and one for cooling. These
      methods will be compared in the study with the goal of selecting the optimal path
      RBL in semiconductor lasers.

PMID- 30184905
TI  - Inverse design and demonstration of an ultracompact broadband dual-mode 3 dB
      power splitter.
AB  - An ultracompact broadband dual-mode 3 dB power splitter using inverse design
      method for highly integrated on-chip mode (de) multiplexing system is proposed
      and experimentally demonstrated. A dual-mode convertor based on subwavelength
      axisymmetric three-branch waveguide is utilized to convert TE0 and TE1 to three
      intermediate fundamental modes. The axisymmetric topology constraint of the
      nanostructures enables the optimized device to achieve a strict 50:50 splitting
      ratio over a broad wavelength range from 1.52 to 1.60 um. The fabricated device
      occupied a compact footprint of only 2.88 um * 2.88 um. The measured average
      excess losses and crosstalks for both modes were respectively less than 1.5 dB
      and -20 dB from 1.52 to 1.58 um for both TE0 and TE1, which are consistent with
      the numerical simulations.

PMID- 30184906
TI  - Generation of vector beams using spatial variation nanoslits with linearly
      polarized light illumination.
AB  - Vector beams (VBs) that possess nonuniform polarization distributions in space
      have various applications. In view of the utilization of the circularly polarized
      light in generating VBs based on the metallic structures, this paper proposes an
      approach to generate VBs using metallic nanoslits with linearly polarized light
      illumination. These nanoslits are located on two concentric circular orbits, and
      the nanoslits on the inner circle are perpendicular to the ones in the outer
      circle. The linearly polarized light is effectively changed into the rotational
      symmetric VBs by rotating these orthogonal nanoslits, and the polarization order
      of the VBs can be adjusted by changing the rotation angles of nanoslits. The
      detailed theoretical analysis provides the basis for the conversion from the
      linearly polarized light to the VBs. Numerical simulations and experimental
      measurement demonstrate the performance of VB generators. This paper's proposed
      method has advantages that include ultrathin and compact structure, convenient
      operation and immediate conversion from linear polarization to VBs, and easier
      expansion of VB applications.

PMID- 30184907
TI  - Evaluation of gold layer configuration for plasmonic fiber grating biosensors.
AB  - Gold-coated fiber Bragg gratings (FBGs) are nowadays a mature technology for lab
      on-fiber sensing based on surface plasmon resonance (SPR) excitation. Tilted FBGs
      bring valuable assets such as easy light injection, remote operation in very
      small volumes of analytes and immunity to temperature fluctuations. Different
      gold configurations have been reported to date, without considering their
      relative performances in terms of biochemical sensing. In this work, we
      experimentally study the impact of the gold coating on the cladding mode
      distribution in the tilted FBG amplitude spectrum and subsequently on its
      sensitivity to cytokeratins used as biomarkers for cancer diagnosis. Some
      relevant configurations of gold coatings are produced and tested, relying on both
      the sputtering and electroless plating (ELP) processes. The obtained results
      confirm that the coating thickness and its roughness drive the biosensing
      performances. The experimental limit of detection for cytokeratins 17 sensing
      reaches 14 fM for the most sensitive configurations.

PMID- 30184908
TI  - Optically pumped rare-earth-doped Al2O3 distributed-feedback lasers on silicon
      [Invited].
AB  - This paper reviews recent progress in the field of optically pumped rare-earth
      doped channel waveguide lasers, with a focus on operation utilizing distributed
      feedback resonators on silicon wafers. Rare-earth-doped amorphous aluminum oxide
      thin films have been deposited onto silicon wafers by RF reactive co-sputtering
      from metallic Al and rare-earth targets, the spectroscopy and optical gain of
      Er3+, Yb3+, Nd3+, and Tm3+ ions has been investigated, and the near-infrared
      laser transitions near 1 MUm in Yb3+, 1.5 MUm in Er3+, and 2 MUm in Tm3+ and Ho3+
      have been demonstrated. Output power between a few MUW and hundreds of mW have
      been achieved in different waveguide geometries, and ultranarrow-linewidth laser
      operation has been demonstrated.

PMID- 30184909
TI  - Fiber-optic transmission and networking: the previous 20 and the next 20 years
      [Invited].
AB  - Celebrating the 20th anniversary of Optics Express, this paper reviews the
      evolution of optical fiber communication systems, and through a look at the
      previous 20 years attempts to extrapolate fiber-optic technology needs and
      potential solution paths over the coming 20 years. Well aware that 20-year
      extrapolations are inherently associated with great uncertainties, we still hope
      that taking a significantly longer-term view than most texts in this field will
      provide the reader with a broader perspective and will encourage the much needed
      out-of-the-box thinking to solve the very significant technology scaling problems
      ahead of us. Focusing on the optical transport and switching layer, we cover
      aspects of large-scale spatial multiplexing, massive opto-electronic arrays and
      holistic optics-electronics-DSP integration, as well as optical node
      architectures for switching and multiplexing of spatial and spectral
      superchannels.

PMID- 30184910
TI  - Optical coherence tomography in Optics Express [Invited].
AB  - Optical coherence tomography (OCT) is one of the most successful technologies in
      the history of biomedical optics. Optics Express played an important role in
      communicating groundbreaking technological achievements in the field of OCT, and,
      conversely, OCT papers are among the most frequently cited papers published in
      Optics Express. On the occasion of the 20th anniversary of the journal, this
      review analyzes the reasons for the success of OCT papers in Optics Express and
      discusses possible motivations for researchers to submit some of their best OCT
      papers to the journal.

PMID- 30184911
TI  - Large scale quantum key distribution: challenges and solutions [Invited].
AB  - Quantum key distribution (QKD) together with one time pad encoding can provide
      information-theoretical security for communication. Currently, though QKD has
      been widely deployed in many metropolitan fiber networks, its implementation in a
      large scale remains experimentally challenging. This letter provides a brief
      review on the experimental efforts towards the goal of global QKD, including the
      security of practical QKD with imperfect devices, QKD metropolitan and backbone
      networks over optical fiber and satellite-based QKD over free space.

PMID- 30184912
TI  - 20th anniversary review articles: concluding a year of celebration.
AB  - Editor-in-Chief Andrew M. Weiner summarizes the full list of invited review and
      perspective articles for Optics Express's 20th Anniversary celebration,
      completing the year of special content.

PMID- 30184913
TI  - Ultrathin mono-resonant nano photovoltaic device for broadband solar conversion.
AB  - Nano-resonators can be used in photovoltaics to drastically improve the ability
      of the device to absorb light and generate photo-carriers, therefore enabling a
      reduction of the absorber volume. Conventionally, the harvest of the spectrally
      broad solar spectrum is achieved via the tedious engineering of multiple optical
      resonances. In this paper, we propose a breakthrough approach, which consists in
      reducing the solar spectral range with a spectral conversion layer to match only
      one resonance that can then be easily designed. We use a Maxwell solver and a ray
      tracing code to optimize the nano-resonator and its spectral converter. We show
      that 66.2% optical efficiency can be theoretically achieved in less than 40 nm
      mean thick absorber while leading to device design enabling collection of photo
      generated carriers.

PMID- 30184914
TI  - Propagation of sensor noise in oceanic hyperspectral remote sensing.
AB  - In previous works, the authors have shown via numerical simulation that sensor
      noise, even assuming otherwise perfect knowledge of the environment, can cause
      large scale variations in the retrieval of concentrations of biophysical
      parameters in a water body, and also investigated methods for using statistical
      measures (such as the Mahalanobis distance) to help mitigate these issues. In
      this work, we derive explicit formulas that can be used to estimate how
      uncertainty in the sensor radiance is propagated to uncertainty in the remote
      sensing reflectanceRrs(lambda), without the need for simulations. In particular,
      the formulas show that the variation in Rrs(lambda)is affected by not only the
      noise characteristics of the sensor, but also by the conditions (atmospheric
      parameters, viewing angles, altitude) under which the data is collected. We
      include validation results for the formulas over a wide range of atmospheric
      conditions, and show by example how the collection conditions can affect the
      uncertainty in Rrs(lambda).

PMID- 30184915
TI  - Bragg reflectors for measuring optical parameters of layers of metamorphic
      InAlGaAs/GaAs heterostructures.
AB  - Spectroscopic reflectometry was used within 700-1600 nm wavelength range to
      investigate dispersion curves for In0.06Al0.94As, In0.06Al0.1Ga0.84As, and
      In0.06Ga0.94As layers, which constituted the purpose-made metamorphic
      InAlGaAs/GaAs Bragg reflector (BR). The procedure for determining the refractive
      index based on analyzing variations in cross-correlation coefficient obtained for
      reflection coefficient calculated and experimental dependences is presented. The
      sensitivity of the proposed method for variations in refractive index was
      investigated depending on the number of BR periods, the extinction coefficient of
      the layers of BR, and the wavelength range with respect to the main reflection
      maximum.

PMID- 30184916
TI  - Simulation of the microstructural characteristics of saltwater turbulence in a
      water tank.
AB  - This study simulated the generation and evolution of saltwater turbulence within
      a water tank. By pouring fresh water over saltwater in the tank, a layer of
      saline water with a fixed gradient was created. Convective turbulence was then
      formed by heating the bottom of the tank. The temperatures at different heights
      were measured using eight thermocouples; thus, the average temperatures and
      temperature fluctuations at different heights were calculated. The salinity
      profile was obtained by moving a conductivity probe up and down to measure the
      conductivity. Two-dimensional light intensity grayscale images were recorded
      after transmitting a collimated laser beam through the water tank, after which
      the normalized variance and power spectra of the light intensity fluctuations at
      different heights were calculated. The results showed that the saltwater in the
      tank could be divided by height into two layers, namely, the mixed layer and
      entrainment zone, according to the profiles of the average temperature and
      average salinity under the experimental conditions. Different portions of the
      images showed different characteristics. The part corresponding to the saltwater
      mixed layer was similar to that corresponding to the mixed layer in the fresh
      water experiment. However, a two-peak structure was observed in the curve of the
      normalized light intensity spectrum calculated from the grayscale values in the
      part corresponding to the bottom of the entrainment zone, whereas a two-peak
      structure was not found in the light intensity fluctuation spectrum corresponding
      to the mixed layer. According to the refractive index fluctuation spectrum model,
      one peak was due to temperature fluctuations, and the other peak was due to
      salinity fluctuations. It can be concluded that the salinity contribution to the
      refractive index fluctuation in the entrainment zone was larger than that in the
      mixed layer. Moreover, spectral analysis showed that in the saltwater, the inner
      scale of turbulent temperature fluctuation was approximately 1.9 mm, while the
      inner scale of turbulent salinity fluctuation was approximately 0.1 mm. These
      findings will be helpful for us to understand the microstructural characteristics
      of seawater turbulence and guide the implementation of optical transmission
      experiments in seawater.

PMID- 30184917
TI  - Tomographic approach for the quantitative scene reconstruction from light field
      images.
AB  - Current computational methods for light field photography model the ray-tracing
      geometry inside the plenoptic camera. This representation of the problem, and
      some common approximations, can lead to errors in the estimation of object sizes
      and positions. We propose a representation that leads to the correct
      reconstruction of object sizes and distances to the camera, by showing that light
      field images can be interpreted as limited angle cone-beam tomography
      acquisitions. We then quantitatively analyze its impact on image refocusing,
      depth estimation and volumetric reconstructions, comparing it against other
      possible representations. Finally, we validate these results with numerical and
      real-world examples.

PMID- 30184918
TI  - eHoloNet: a learning-based end-to-end approach for in-line digital holographic
      reconstruction.
AB  - It is well known that in-line digital holography (DH) makes use of the full pixel
      count in forming the holographic imaging. But it usually requires phase-shifting
      or phase retrieval techniques to remove the zero-order and twin-image terms,
      resulting in the so-called two-step reconstruction process, i.e., phase recovery
      and focusing. Here, we propose a one-step end-to-end learning-based method for in
      line holography reconstruction, namely, the eHoloNet, which can reconstruct the
      object wavefront directly from a single-shot in-line digital hologram. In
      addition, the proposed learning-based DH technique has strong robustness to the
      change of optical path difference between reference beam and object light and
      does not require the reference beam to be a plane or spherical wave.

PMID- 30184919
TI  - Remote and autonomous temperature measurement based on 3D liquid crystal
      microlasers.
AB  - We demonstrate non-contact temperature measurement with one tenth of a kelvin
      precision at distances of several meters using omnidirectional laser emission
      from dye-doped cholesteric liquid crystal droplets freely floating in a fluid
      medium. Upon the excitation with a pulsed laser the liquid crystal droplet emits
      laser light due to 3D Bragg lasing in all directions. The spectral position of
      the lasing is highly dependent on temperature, which enables remote and contact
      less temperature measurement with high precision. Both laser excitation and
      collection of light emitted by microlasers is performed through a wide telescope
      aperture optics at a distance of up to several meters. The optical excitation
      volume, where the droplets are excited and emitting the laser light is of the
      order of ten cubic millimeters. The measurement is performed with ten second
      accumulation time, when several droplets pass through the excitation volume due
      to their motion. The time of measurement could easily be shortened to less than a
      second by increasing the rate of the excitation laser. Since the method is based
      solely on measuring the spectral position of a single and strong laser line, it
      is quite insensitive to scattering, absorption and background signals, such as
      autofluorescence. This enables a wide use in science and industry, with a
      detection range exceeding tens of meters.

PMID- 30184920
TI  - X-ray phase contrast observation of solidification and hot crack propagation in
      laser spot welding of aluminum alloy.
AB  - The inner characteristics of solidification and crack propagation in laser spot
      welding of four representative aluminum alloys, A1050, A2024, A5083 and A6061,
      were firstly observed with the X-ray phase contrast method. Keyhole disappeared
      within 1 ms after the laser was shut down. The solidification process finished in
      2 ms for A1050, 3 ms for A2024, 5 ms for A5083, and 3 ms for A6061, respectively.
      Longitudinal view area of the molten pool decreased as the thermal conductivity
      increased, while the average solidification rate increased with increase of the
      thermal conductivity. Hot crack was observed to propagate from the bottom to the
      upper surface in the center of spot weld of A2024, A5083, and A6061, which was
      also the first in situ observation of crack during the welding process. Both the
      SEM, EBSD and Micro-X-ray computed tomography (CT) results validated that there
      was a crack propagation in the spot weld, and the mechanism for this crack
      formation was discussed. This paper provides a better understanding of
      solidification and crack formation in laser manufacturing.

PMID- 30184921
TI  - Extracavity pumped parametric Raman nanosecond crystalline anti-Stokes laser at
      954 nm with collinear orthogonally polarized beam interaction at tangential phase
      matching.
AB  - The extracavity parametric Raman CaCO3 anti-Stokes laser at 954 nm excited by two
      orthogonally polarized (pump and probe) equal frequency laser beams was proposed
      and investigated. Tangential phase matching conditions for the orthogonally
      polarized Raman components four-wave mixing in the CaCO3 crystal at stimulated
      Raman scattering (SRS) under 1064-nm excitation were theoretically studied and
      applied for a novel nanosecond parametric Raman laser allowing to increase the
      954-nm anti-Stokes generation efficiency. In agreement with the theoretical
      modeling, using the high-Q external cavity scheme we have experimentally achieved
      the highest optical-to-optical (1064 nm to 954 nm) efficiency of 4% in comparison
      with the known crystalline parametric Raman anti-Stokes lasers. The ~3 ns anti
      Stokes output pulse energy was 0.3 mJ with high beam quality factor M2 = 1.1 *
      1.2.

PMID- 30184922
TI  - Highly selective ultraviolet aluminum plasmonic filters on silicon.
AB  - We report the use of aluminum patterning to make highly selective UV bandpass
      filters. We design and fabricate a periodic array of nanoholes in Al thin film on
      a bare silicon substrate as an analog for potential integration with a Si
      photodetector. Arrays were designed to operate in the wavelength range of 200-400
      nm. Our results show that we can obtain a single dominant peak filter with a
      linewidth of 30 nm at normal incidence, in contrast to similar structures on
      glass substrates, where multiple modes influence the UV spectrum. Varying the
      angle of incidence is shown to split the plasmonic mode and further decrease the
      linewidth of the maximum wavelength mode down to 10 nm. Our results therefore
      show high potential for applications in solid-state image sensors for astronomy
      and planetary studies.

PMID- 30184923
TI  - Multi-user access in wireless optical communication system.
AB  - In this paper, a multipoint-to-point system consisting K users and a central node
      over wireless optical communication (WOC) channel is analyzed. The scenario
      focused on is that there is simultaneous communication from a number of users to
      the central node. As a powerful solution, we utilize non-orthogonal multiple
      access (NOMA) technique in the system. Although the superiority of NOMA in radio
      frequency (RF) system has been greatly considered, the NOMA in WOC still needs
      further research due to the special features of WOC, especially the non-broadcast
      nature of optical beam and the vulnerable turbulence channel. With the special
      features of WOC in mind, system is evaluated in terms of outage probability, bit
      error rate and ergodic sum rate. In addition, we theoretically prove that NOMA
      outperforms orthogonal multiple access (OMA), and the performance gain increases
      with the increase of turbulence strength. Hence, NOMA is more suitable for WOC,
      especially in strong turbulence channel. Moreover, we also analyze the user
      pairing scheme. Monte Carlo simulations have been done, which match quite well
      with the theoretical analysis.

PMID- 30184924
TI  - Transmitter and receiver DSP for 112 Gbit/s PAM-4 amplifier-less transmissions
      using 25G-class EML and APD.
AB  - The transmission performance of 112 Gbit/s PAM-4 signal with commercial 25 G
      class EML and APD is experimentally studied by using advanced digital signal
      processing (DSP) algorithms, i.e. pre-equalization (Pre-EQ), error-table based
      pre-correction (ETC), least-mean square (LMS) based equalization, direct
      detection faster than Nyquist (DD-FTN) algorithm. Among them, Pre-EQ and ETC are
      implemented at the transmitter, and ETC is a symbol-pattern-dependent pre
      compensation algorithm based on the look-up-table approach. In order to obtain
      these pre-compensated parameters readily, a joint equalization and error table
      generation (JEEG) module is proposed. Employing the combination of ETC, LMS, and
      DD-FTN, a single line 112 Gbit/s PAM-4 40 km amplifier-less transmission with a
      record receiver sensitivity of -16.6 dBm (at 7% HD-FEC threshold) is
      experimentally demonstrated. In addition, the computational complexities of
      different DSP schemes are analyzed and discussed in detail. The receiver
      computational complexity can be effectively reduced by employing appropriate ETC
      and Pre-EQ in the transmitter.

PMID- 30184926
TI  - Real-time optofluidic surface-enhanced Raman spectroscopy based on a graphene
      oxide/gold nanorod nanocomposite.
AB  - We demonstrate a glass microcapillary fiber as an optofluidic platform for
      surface enhanced Raman spectroscopy (SERS), the inner walls of which are coated
      with a graphene oxide (GO)/gold nanorod (AuNR) nanocomposite. A simple thermal
      method is used for the coating, allowing for the continuous deposition of the
      nanocomposite without surface functionalization. We show that the AuNRs can be
      directly and nondestructively identified on the GO inside the capillaries via
      identification of the Au-Br SERS peak, as Br- ions from the AuNR synthesis remain
      on their surface. The coated microcapillary platform is, then, used as a stable
      SERS substrate for the detection of Rhodamine 6G (R6G) and Rhodamine 640 (RH640)
      at concentrations down to 10-7 and 10-9 M, respectively. As the required sample
      volumes are as low as a few hundred nanoliters, down to ~75 femtograms of analyte
      can be detected. The fiber also allows for the detection of the molecules at
      acquisition times as low as 0.05 s, indicating the platform's suitability for
      real-time sensing.

PMID- 30184925
TI  - Matrix heater in the gravitational wave observatory GEO 600.
AB  - Large scale laser interferometric gravitational wave detectors (GWDs), such as
      GEO 600 require high quality optics to reach their design sensitivity. The
      inevitable surface imperfections, inhomogeneities, and light-absorption induced
      thermal lensing in the optics, can convert laser light from the fundamental mode
      to unwanted higher order modes, and pose challenges to the operation and
      sensitivity of the GWDs. Here we demonstrate the practical implementation of a
      thermal projection system which reduces those unwanted effects via targeted
      spatial heating of the optics. The thermal projector consists of 108 individually
      addressable heating elements which are imaged onto the beam splitter of GEO 600.
      We describe the optimization of the spatial heating profile and present the
      obtained results.

PMID- 30184927
TI  - Frequency-dependent skin penetration depth of terahertz radiation determined by
      water sorption-desorption.
AB  - A multilayered water-skin model is used to experimentally verify a new sensing
      method for determining the skin penetration depth of radiation with 0.1-0.9
      terahertz (THz) frequencies. A water overlayer is dripped on a skin sample to
      form a multilayered structure for dynamically measuring the reflected THz-wave
      amplitude during water desorption. Skin penetration depths can be successfully
      derived by using the multilayered water-skin model and by considering the
      measured reflectivity, water dielectric constants, and effective thicknesses of
      the water overlayer on the skin sample. The maximum penetration depth is
      approximately 0.3 mm and is obtained with wave frequencies of 0.4-0.6 THz. This
      penetration depth encompasses the stratum corneum (SC) and part of the epidermis.
      The high penetration depth of 0.4-0.6 THz waves is also confirmed in the dried
      and damaged SC.

PMID- 30184928
TI  - Superfocusing of terahertz wave through spoof surface plasmons.
AB  - In this paper, we propose and numerically demonstrate a new way to realize
      superfocusing of terahertz waves via the spoof surface plasmons (SSP). With the
      assist of a modified subwavelength metallic grating, a near-field rapid
      oscillation can be formed, originating from the Fabry-Perot resonances due to the
      reflection of SSP waves at terminations. We show that the field pattern of
      oscillation on textured metallic surface can be engineered by adjusting groove
      width and grating number. This produces a desired modulation of phase and
      amplitude for the radiationless electromagnetic interference (REI) focusing. The
      effective focusing depth through the corrugated metal is evaluated by the full
      width-half-maximum (FWHM) beamwidth. At the situation of third-order Fabry-Perot
      resonance, the FWMH reaches up to 0.069lambda at a distance of 0.1lambda,
      improving the beamwidth by more than 540% compared with a single slit. The FWHM
      is optimized to 0.06lambda as the order of Fabry-Perot resonance becomes seven,
      leading to the superfocusing metric of 1.67. On the basis of this, we further
      show the focusing ability can be held on the ultra-thin metallic grating. Two
      dimensional subwavelength focusing behavior is also numerically verified. Our
      study may extend the working distance of sensing and super-resolution imaging
      devices at terahertz frequency.

PMID- 30184929
TI  - Testing the photon-number statistics of a quantum key distribution light source.
AB  - A commonly held tenet is that lasers well above threshold emit photons in a
      coherent state, which follow Poissonian statistics when measured in photon
      number. This feature is often exploited to build quantum-based random number
      generators or to derive the secure key rate of quantum key distribution systems.
      Hence the photon number distribution of the light source can directly impact the
      randomness and the security distilled from such devices. Here, we propose a
      method based on measuring correlation functions to experimentally characterize a
      light source's photon statistics and use it in the estimation of a quantum key
      distribution system's key rate. This promises to be a useful tool for the
      certification of quantum-related technologies.

PMID- 30184930
TI  - Sub-200 fs soliton mode-locked fiber laser based on bismuthene saturable
      absorber.
AB  - Few-layer bismuthene is an emerging two-dimensional material in the fields of
      physics, chemistry, and material science. However, its nonlinear optical property
      and the related photonics device have been seldom studied so far. Here, we
      demonstrate a sub-200 fs soliton mode-locked erbium-doped fiber laser (EDFL)
      using a microfiber-based bismuthene saturable absorber for the first time, to the
      best of our knowledge. The bismuthene nanosheets are synthesized by the
      sonochemical exfoliation method and transferred onto the taper region of a
      microfiber by the optical deposition method. Stable soliton pulses centered at
      1561 nm with the shortest pulse duration of about 193 fs were obtained. Our
      findings unambiguously imply that apart from its fantastic electric and thermal
      properties, few-layer bismuthene may also possess attractive optoelectronic
      properties for nonlinear photonics, such as mode-lockers, Q-switchers, optical
      modulators and so on.

PMID- 30184931
TI  - Polarization-insensitive phase conjugation using single pump Bragg-scattering
      four-wave mixing in semiconductor optical amplifiers.
AB  - We explain the generation of four wave mixing (FWM) components at the front and
      back facets of semiconductor optical amplifiers (SOAs) based on the Bragg
      scattering from the propagating gratings in the SOAs. We propose a counter
      propagating cross-polarized degenerate pumping scheme for the polarization
      insensitive conjugate generation, simultaneously in both input and output ports
      of the SOA for the first time. The corresponding Bragg scattering processes along
      with the phase matching conditions are described and the detuning performance of
      the generated conjugate in either port are experimentally validated. Polarization
      insensitive phase conjugate generation at both input and output ports of the SOA
      through Bragg scattering FWM is further demonstrated.

PMID- 30184932
TI  - Photon-limited face image super-resolution based on deep learning.
AB  - With one single photon camera (SPC), imaging under ultra weak-lighting conditions
      may have wide-ranging applications ranging from remote sensing to night vision,
      but it may seriously suffer from the problem of under-sampled inherent in SPC
      detection. Some approaches have been proposed to solve the under-sampled problem
      by detecting the objects many times to generate high-resolution images and
      performing noise reduction to suppress the Poission noise inherent in low-flux
      operation. To address the under-sampled problem more effectively, a new approach
      is developed in this paper to reconstruct high-resolution images with lower-noise
      by seamlessly integrating low-light-level imaging with deep learning. In our new
      approach, all the objects are detected only once by SPC, where a deep network is
      learned to reduce noise and reconstruct high-resolution images from the detected
      noisy under-sampled images. In order to demonstrate our proposal is feasible, we
      first select a special category to verify by experiment, which are human faces.
      Such deep network is able to recover high-resolution and lower-noise face images
      from new noisy under-sampled face images and the resolution can achieve 4* up
      scaling factor. Our experimental results have demonstrated that our proposed
      method can generate high-quality images from only ~0.2 detected signal photon per
      pixel.

PMID- 30184933
TI  - Transport of spatial squeezing through an optical waveguide.
AB  - Multi-core optical fibers are readily used in endoscopic devices to transmit
      classical images. As an extension to the quantum domain, we study the
      transmission of the spatial quantum fluctuations of light through a conduit made
      of the ordered packing of thousands of fibers. Starting from twin beams that are
      correlated in their local intensity fluctuations, we show that, in the limit of a
      high density of constituent fiber cores, the intensity-difference squeezing
      present in arbitrary matching regions of the beams is preserved when one of the
      beams is sent through the conduit. The capability of using fiber bundles to
      transport quantum information encoded in the spatial degrees of freedom could
      bring guided-light technology to the emergent field of quantum imaging.

PMID- 30184934
TI  - Field implementation of long-distance quantum key distribution over aerial fiber
      with fast polarization feedback.
AB  - Quantum key distribution with polarized qubits has not yet been realized over the
      aerial fiber, due to rapid polarization changes. Here, we report our recent work
      towards quantum communication through an aerial fiber channel. We designed a fast
      polarization feedback module featuring high efficiency, fast speed, and good
      stability. With this module, we implemented long-distance quantum key
      distribution over different types of aerial fiber links based on polarization
      encoding. Our work takes a significant step towards the application of quantum
      communications in complex environments.

PMID- 30184935
TI  - Design of a tapered slot waveguide dielectric laser accelerator for sub
      relativistic electrons.
AB  - We propose a dielectric laser accelerator design based on a tapered slot
      waveguide structure for sub-relativistic electron acceleration. This tapering
      scheme allows for straightforward tuning of the phase velocity of the
      accelerating field along the propagation direction, which is necessary for
      maintaining synchronization with electrons as their velocities increase.
      Furthermore, the non-resonant nature of this design allows for better tolerance
      to experimental errors. We also introduce a method to design this continuously
      tapered structure based on the eikonal approximation, and give a working example
      based on realistic experimental parameters.

PMID- 30184936
TI  - Diffraction glare points: principle and application in particle sizing.
AB  - A novel particle sizing method based on diffraction glare points is proposed,
      which is independent of the refractive index of particle. With geometric optics
      approximation, the relationship between distance of diffraction glare points and
      particle size is obtained. In analysis of measurement parameters, we find that 4
      degrees  is the optimal central scattering angle for measuring wide size range
      particles based on diffraction glare points. With an experimental system at this
      angle, diffraction glare points of four kinds of standard particles were imaged.
      The relative deviations between measured and nominal particle size were not
      greater than 2%, less than that using reflection glare points, demonstrating
      validity and advantage of the particle sizing method based on distance of
      diffraction glare points.

PMID- 30184937
TI  - Computational imaging enables a "see-through" lens-less camera.
AB  - Conventional cameras obscure the scene that is being recorded. Here, we place an
      image sensor (with no lens) on the edge of a transparent window and form images
      of the object seen through that window. This is enabled first, by the collection
      of scattered light by the image sensor, and second, by the solution of an inverse
      problem that represents the light scattering process. Thereby, we were able to
      form simple images, and demonstrate a spatial resolution of about 0.1 line
      pairs/mm at an object distance of 150mm with depth-of-focus of at least 10mm. We
      further show imaging of two types of objects: an LED array and a conventional LCD
      screen. Finally, we also demonstrate color and video imaging.

PMID- 30184938
TI  - Fabrication of three-dimensionally ordered macroporous TiO2 film and its
      application in quantum dots-sensitized solar cells.
AB  - Engineering of TiO2 photoanode is an important strategy for increasing the
      photovoltaic conversion efficiency of quantum dots-sensitized solar cells
      (QDSSCs). In this work, three-dimensional ordered macroporous (3DOM) TiO2 films
      are fabricated by the controlled infiltrating-calcination method using the close
      packed polystyrene spheres colloidal crystals as templates. The as-prepared
      macroporous TiO2 films are then applied as the photoanode in colloidal CdSe
      QDSSCs. This structure not only facilitates the penetration of thioglycolic acid
      capped CdSe QDs, and thus achieving a high coverage of the internal surface with
      QDs sensitizer, but also exhibits a photonic band gap with tunable positions,
      which could enhance the light absorption. As a result, the liquid-junction QDSSCs
      assembled with the CdSe sensitized 3DOM TiO2 yields a power conversion efficiency
      of 3.60% under solar illumination of 100 mW cm-2, and this value is much higher
      than that of the device using nanoporous TiO2 photoanode (1.82%). Our results
      indicate that the 3DOM TiO2 is a promising candidate for the construction of high
      efficiency QDSSCs.

PMID- 30184939
TI  - Absorption enhancement in methylammonium lead iodide perovskite solar cells with
      embedded arrays of dielectric particles.
AB  - In the field of hybrid organic-inorganic perovskite based photovoltaics, there is
      a growing interest in the exploration of novel and smarter ways to improve the
      cells light harvesting efficiency at targeted wavelength ranges within the
      minimum volume possible, as well as in the development of colored and/or
      semitransparent devices that could pave the way both to their architectonic
      integration and to their use in the flowering field of tandem solar cells. The
      work herein presented targets these different goals by means of the theoretical
      optimization of the optical design of standard opaque and semitransparent
      perovskite solar cells. In order to do so, we focus on the effect of harmless,
      compatible and commercially available dielectric inclusions within the absorbing
      material, methylammonium lead iodide (MAPI). Following a gradual and systematic
      process of analysis, we are capable of identifying the appearance of collective
      and hybrid (both localized and extended) photonic resonances which allow to
      significantly improve light harvesting and thus the overall efficiency of the
      standard device by above 10% with respect to the reference value while keeping
      the semiconductor film thickness to a minimum. We believe our results will be
      particularly relevant in the promising field of perovskite solar cell based
      tandem photovoltaic devices, which has posed new challenges to the solar energy
      community in order to maximize the performance of semitransparent cells, but also
      for applications focusing on architectonic integration.

PMID- 30184940
TI  - Optical design and demonstration of microtracking CPV module with bi-convex
      aspheric lens array.
AB  - A microtracking concentrator photovoltaics (CPV) module with a bi-convex aspheric
      lens array was designed, and its performance was numerically and experimentally
      verified. The lens shape was optimized considering the yearly incidence
      characteristics of direct solar radiation. The lens optimized at 127 * was found
      to converge 68.7% of the yearly cumulative direct solar radiation to solar cells
      and to be robust against changes in installation azimuth and tilt angles. The
      incidence-angle characteristics of a prototype lens agreed well with the design
      analysis. In an outdoor test using a prototype microtracking CPV module with an
      optimized lens and a triple-junction solar cell, the power generation was 1.32
      times higher than that of the 17%-efficient Si cell and nearly 30% module
      conversion efficiency was achieved under clear sky conditions.

PMID- 30184941
TI  - Performance of a dielectric PVT concentrator for building-facade integration.
AB  - Concentrating photovoltaic-thermal (CPVT) systems, which can be integrated on
      buildings facades and use low-accuracy trackers and standard cells, have the
      potential to produce cost-effective electricity and heat. In this paper, a
      refractive cylindrical CPVT module with cells directly immersed in deionized
      water (DIW) or isopropyl alcohol (IPA) is designed, fabricated and experimentally
      tested. The interfaces between the cylinder and the fluids cavity have been
      optimized to maximize optical efficiency and irradiance uniformity, obtaining
      better results for a geometric concentration of 10x and IPA. The system achieves
      an optical efficiency of 81%, an acceptance angle of 1.07 degrees  and a non
      uniformity coefficient of 0.13.

PMID- 30184942
TI  - Blind Poissonian reconstruction algorithm via curvelet regularization for an FTIR
      spectrometer.
AB  - An FTIR spectrometer often suffers from common problems of band overlap and
      Poisson noises. In this paper, we show that the issue of infrared (IR) spectrum
      degradation can be considered as a maximum a posterior (MAP) problem and solved
      by minimized a cost function that includes a likelihood term and two prior terms.
      In the MAP framework, the likelihood probability density function (PDF) is
      constructed based on the observed Poisson noise model. A fitted distribution of
      curvelet transform coefficient is used as spectral prior PDF, and the instrument
      response function (IRF) prior is described based on a Gauss-Markov function.
      Moreover, the split Bregman iteration method is employed to solve the resulting
      minimization problem, which highly reduces the computational load. As a result,
      the Poisson noises are perfectly removed, while the spectral structure
      information is well preserved. The novelty of the proposed method lies in its
      ability to estimate the IRF and latent spectrum in a joint framework, thus
      eliminating the degradation effects to a large extent. The reconstructed IR
      spectrum is more convenient for extracting the spectral feature and interpreting
      the unknown chemical or biological materials.

PMID- 30184944
TI  - Compact design for optical-see-through holographic displays employing holographic
      optical elements.
AB  - Holographic AR display is a promising technology for head-mounted display
      devices. However, it usually has a complicated optical system and a large form
      factor, preventing it from widespread applications. In this work, we propose a
      flat-panel design to produce a compact holographic AR display, where traditional
      optical elements are replaced by two holographic optical elements (HOEs). Here,
      these two thin HOEs together perform the optical functions of a beam expander, an
      ocular lens, and an optical combiner. Without any bulky traditional optics, our
      design could achieve a compact form factor that is similar to a pair of glasses.
      We also implemented a proof-of-concept prototype to verify its feasibility. Being
      compact, lightweight and free from accommodation-convergence discrepancy, our
      design is promising for fatigue-free AR displays.

PMID- 30184943
TI  - Security enhancement for OFDM-PON using Brownian motion and chaos in cell.
AB  - We propose a novel security enhancement technique for a physical layer secure
      orthogonal frequency division multiplexed passive optical network (OFDM-PON)
      based on three-dimensional Brownian motion and chaos in cell (3DBCC). This method
      confuses an OFDM symbol via transforming it into a 3D symbol matrix and a 3D cell
      matrix with different size lengths. Different dividing-confusion rules then
      generate different complementary cumulative distribution functions (CCDFs) of
      peak-to-average power ratio (PAPR). And we can pre-estimate bit error rate (BER)
      performance by calculating the CCDF values. We also find that the processing time
      decreases with the matrix's side length decreasing simultaneously. A new weighted
      comprehensive value (Qw) is further used to evaluate the overall performance
      between the processing time and the BER. Finally, an experiment successfully
      demonstrates a physical layer secure OFDM signal transmission with 22.06-Gb/s
      data rate over a 25.4-km standard single mode fiber (SSMF). These results
      indicate that cell (53) has the weighted optimum overall performance, which
      verifies that the proposed encryption technique is promising for building a
      physical layer security enhanced OFDM-PON system with a low processing time delay
      and a good BER for future access network systems.

PMID- 30184945
TI  - Spectro-temporal dispersion management of femtosecond pulses for fiber-optic two
      photon endomicroscopy.
AB  - The emerging fiber-optic two-photon endomicroscopy technology holds a strong
      promise for enabling translational applications of nonlinear optical imaging.
      Effective femtosecond pulse dispersion management is critical for achieving high
      quality imaging. Here we report systematic analyses and performance
      characterization of a dual-fiber spectro-temporal dispersion management scheme
      involving a grating pair as the pulse stretcher. Compared with conventional
      linear-only compensation, the grating-based spectro-temporal compensation also
      takes into account nonlinear effects and enhances the two-photon signal by ~3
      fold as experimentally demonstrated. Numerical simulations were carried out to
      systematically investigate the influence of several key design parameters on the
      overall compensation efficacy. Furthermore, comprehensive performance comparison
      with an ideal grism-pair counterpart reveals that a grating-pair stretcher
      affords much higher power throughput and thus is preferable for portable
      endomicroscopy systems with limited laser source power.

PMID- 30184946
TI  - Power scalability of linearly polarized random fiber laser through polarization
      rotation-based Raman gain manipulation.
AB  - Random fiber laser based on Raman gain and random distributed feedback has drawn
      great attention in recent years. One of the most widely-studied fields is to
      improve the optical efficiency and the output power. However, the power scaling
      of a random fiber laser is instinctively restricted by the high order Stokes
      generation. In this manuscript, we propose a simple yet effective method, which
      employs a homemade all-fiber Lyot filter to manipulate the polarization dependent
      Raman gain, thus increasing the threshold of the 2nd-order Stokes wave and
      enhancing the maximum output power of the linearly polarized random fiber laser.
      Through reliable theoretical analysis, we optimize the design of the wavelength
      dependent Lyot filter. Moreover, the performance of the filter and the power
      scaling capability of the linearly polarized random fiber laser are investigated
      in detail. A proof-of-principle experiment is carried out by inserting the
      homemade Lyot filter into a half-opened random fiber laser. The experimental
      results indicate that the 2nd-order Stokes wave can be effectively suppressed,
      and the maximum output power of the 1st-order Stokes wave is significantly
      increased with a range of ~50% (from 43.6 to 63.2 W).

PMID- 30184947
TI  - Photon-pair and heralded single photon generation initiated by a fraction of a 10
      Gbps data stream.
AB  - A fraction of a classical 10 Gigabits-per-second, non-return-to-zero data stream
      at 1.55 micron wavelengths from a standard telecommunications optical transceiver
      was tapped and used to generate photon-pairs and heralded single photons using a
      silicon microring resonator at room temperature. These results show that there
      may be no need for a separate laser to generate high-quality photon pairs for
      quantum applications in a typical optical communications network.

PMID- 30184948
TI  - Transparent coupled membrane metamaterials with simultaneous microwave absorption
      and sound reduction.
AB  - Metamaterials offer a novel strategy to control wave propagation in different
      physical fields ranging from acoustic, electromagnetic, and optical waves to
      static electric and thermal fields. However, fundamental and practical challenges
      still need to be overcome for multi-physical manipulation, especially for
      independent control of acoustic and electromagnetic waves simultaneously. In this
      paper, we propose and experimentally demonstrate a transparent bifunctional
      metamaterial in which acoustic and electromagnetic waves could be engineered
      jointly and individually. Specifically, a transparent composite coupled membrane
      metamaterial is introduced with indium tin oxide (ITO) patterns coated on the top
      and bottom membranes, giving rise to simultaneous electromagnetic wave
      dissipation and sound reduction. Our results could help broaden the current
      research scope for multiple disciplines and pave the way for the development of
      multi-functional devices in new applications.

PMID- 30184949
TI  - One-point and multi-line calibration method in laser-induced breakdown
      spectroscopy.
AB  - The calibration-free laser-induced breakdown spectroscopy (CF-LIBS) and its
      variations are low cost, short time consumption, and high adaptability. However,
      seeking a more flexible and simple quantitative analysis method remains a
      challenge. A one-point and multi-line calibration (OP-MLC) was presented as a
      simple quantitative analysis method of LIBS. The results showed that OP-MLC-LIBS
      method can achieve quantitative analysis using only one standard sample, and the
      average relative errors (AREs) are 9, 22, 21 and 36% for Mn, Cr, Ni and Ti
      elements in six tested low-alloy steel samples, respectively. The method requires
      neither a large number of standard samples nor complicated calculations, which
      provides a flexible and low-cost quantitative analysis approach for development
      and application of LIBS.

PMID- 30184950
TI  - Unveiling the spin Hall effect of light in Imbert-Fedorov shift at the Brewster
      angle with weak measurements.
AB  - The Imbert-Fedorov (IF) shift is defined as the transverse shift of barycenter of
      the entire beam when a circular or elliptically polarized incident beam is
      reflected. In this work, we examine the IF shift of Gaussian beam at the Brewster
      angle. Interestingly, the spin Hall effect of light takes place in the IF shift
      at the same time. Furthermore, this interesting phenomenon is experimentally
      observed using weak measurements. These findings may have useful applications in
      spin optics.

PMID- 30184951
TI  - Self-marked HCN gas based FBG demodulation in thermal cycling process for
      aerospace environment.
AB  - The thermal cycling process experienced by spacecraft during orbital operation
      would lead to deterioration of the demodulation performance of fiber Bragg
      grating (FBG). A new demodulation method based on Fabry-Perot (F-P) filter and
      hydrogen cyanide (HCN) gas is proposed to improve the performance. The method
      skillfully utilizes the self-marked HCN absorption lines as absolute wavelength
      references. In the thermal cycling environment whose temperature ranging from 5
      degrees Cto 65 degrees C,the fluctuation of demodulation wavelength reduces to +/
      2.6 pm, which is improved by 3.1 times compared with traditional method. The
      proposed method also shows a good robustness in the cases of weak light source
      intensity and poor signal-to-noise ratio (SNR) of HCN spectrum.

PMID- 30184952
TI  - Visualize the quality of frozen fish using fluorescence imaging aided with
      excitation-emission matrix.
AB  - The quality monitoring of frozen marine products has become essential in the
      fishery industry, where efficient and effective quality assurance is becoming
      increasingly important. In this study, we proposed a novel method of evaluating
      fish quality by combining the fluorescence excitation-emission matrix (EEM) with
      imaging techniques to visualize the spatial-temporal changes of freshness indices
      such as K-value and taste component IMP content. The result showed that the
      distribution of K-value and IMP content could be visualized with accuracy of R2 =
      0.78 and R2 = 0.83, respectively. Furthermore, this innovative approach was
      applied to differentiate burnt meat, which is a type of abnormal meat found in
      many types of fish, and it was found that burnt meat could be detected even when
      in a frozen condition.

PMID- 30184953
TI  - Close-packed optical vortex lattices with controllable structures.
AB  - As a spatial structured light field, the optical vortex (OV) has attracted
      extensive attention in recent years. In practice, the OV lattice (OVL) is an
      optimal candidate for applications of orbital angular momentum (OAM)-based
      optical communications, microparticle manipulation, and micro/nanofabrication.
      However, traditional methods for producing OVLs meet a significant challenge: the
      OVL structures cannot be adjusted freely and form a close-packed arrangement,
      simultaneously. To overcome these difficulties, we propose an alternative scheme
      to produce close-packed OVLs (CPOVLs) with controllable structures. By borrowing
      the concept of the close-packed lattice from solid-state physics, CPOVLs with
      versatile structures are produced by using logical operations of expanding OV
      primitive cells combined with the technique of phase mask generation. Then, the
      existence of OAM states in the CPOVLs is verified. Furthermore, the energy flow
      and OAM distribution of the CPOVLs are visualized and analyzed. From a light
      field physics viewpoint, this work increases the adjustment dimensions and
      extends the fundamental understanding of the OVL, which will introduce novel
      applications.

PMID- 30184954
TI  - Real-time bidirectional coherent ultra-dense TWDM-PON for 1000 ONUs.
AB  - We propose a bidirectional coherent ultra-dense time/wavelength division
      multiplexing passive optical network (UD-TWDM-PON) scheme for 1000 optical
      network units (ONUs). Then we experimentally demonstrate a bidirectional coherent
      UD-TWDM-PON using real-time FPGA-based transceivers. The power budget of this
      system is evaluated based on 1000 downlink ultra-dense wavelength division
      multiplexing (UD-WDM) channels with 5 GHz channel spacing in C band. The power
      budgets are 28 dB for DP-QPSK format with 10 Gb/s per user and 30 dB for PS-QPSK
      format with 7.5 Gb/s per user after 40 km SSMF transmission. The uplink
      transmission over 40 km SSMF for the 1000 users is also achieved based on 200
      channels with 10 Gb/s per channel under channel spacing of 12.5 GHz in L band.
      Time division multiplexing is performed for the uplink optical signals, where 5
      ONUs share one channel in the uplink. The 24-hour real-time performance testing
      for the bidirectional transmission is also conducted to evaluate the feasibility
      of the real-time FPGA-based transceivers in the proposed UD-TWDM-PON scheme.

PMID- 30184955
TI  - Flexible retinal image formation by holographic Maxwellian-view display.
AB  - The Maxwellian-view display can provide visual information to people with low
      vision because retinal images can be formed independently of the refractive power
      of an eye by using rays converging on its pupil. This study presents the
      holographic Maxwellian-view display, which generates a wavefront converging on
      the pupil and forming images on the retina. The beam convergent point can be
      moved electrically in accordance with the pupil movement, and the beam width in
      the pupil can be changed electrically to control the depth of field of the eye. A
      compact optical system configuration for the holographic Maxwellian-view display
      is also proposed. The prototype system was constructed and experimentally tested.
      Because this holographic technique allows the phase modulation in the pupil, eye
      aberrations can be corrected; thus, retinal images can be formed for eyes with
      astigmatism.

PMID- 30184956
TI  - High-performance dichroic dye-doped flexible cholesteric polymer film optical
      filter for laser protection application.
AB  - High-performance optical filters are quite useful in laser protection application
      that is critical in military and civilian fields for protection of human eyes and
      photonic devices. However, most existing technologies are often angle-dependent
      and complicated, which hinder the useful range of real-time application. Here, we
      report the development of a dichroic dye-doped flexible cholesteric polymer film
      optical filter with double-layer structure consisted of two films with opposite
      handedness for laser protection application. The fabricated films exhibit high
      and stable optical density (>4.6) in large angle range from 0 to 70 degrees ,
      indicating a good angle-independence. The proposed films show excellent stability
      in a broad temperature range from -100  degrees C to 100  degrees C, and high
      mechanical stress up to 9.8 * 105 Pa. As a laser protection, the optical filter
      can resist pulse pump energy up to 110 mJ/pulse, showing a high damage threshold.
      The flexible and free-standing film optical filters as laser protection device
      are integrated by simple fabrication, excellent stability to temperature and
      mechanical stress, angle-independence, high optical density, and good visibility
      simultaneously, showing dramatically application potential in laser protection
      and other flexible photonic devices.

PMID- 30184957
TI  - Capacity analysis for free space coherent optical MIMO transmission systems: with
      and without adaptive optics.
AB  - This paper analyzes the capacity of the free space coherent optical MIMO
      transmission system. Two scenarios are considered (i.e., with and without the
      adaptive optics compensation). It is generally accepted that the adaptive optics
      compensation can significantly improve the system performance, which is
      rigorously true when the MIMO algorithm is not implemented. However, it might not
      be the case in the coherent MIMO systems. When the turbulence strength is weak or
      moderate, this work demonstrates that the phase-only wave-front corrector will
      increase the mean eigen value of the coherent system capacity matrix HHH and make
      the eigen value distribution more even, i.e. it will decrease the maximal eigen
      value while increasing the average eigen value. Hence, the capacity of the system
      with adaptive optics increases when the channel information is not available,
      because the sub-channels are placed with equal powers. When the channel
      information is perfectly available and the water filling algorithm is used to
      optimize the power allocation, the system with adaptive optics could have a
      deteriorated performance as the capacity is more related to the large eigen
      values especially in the low signal to noise ratio (SNR) regime. When the
      turbulence strength is strong, it is found that adaptive optics will decrease
      both the mean and maximal eigen values for the capacity matrix HHH, and therefore
      the system capacity degrades, whether the channel information is available or
      not.

PMID- 30184958
TI  - Multimode fiber Phi-OTDR with holographic demodulation.
AB  - We propose and demonstrate a method to perform quantitative phase-sensitive
      optical time domain reflectometry (Phi-OTDR) using multimode fiber. While most
      Phi-OTDR sensors use single-mode fiber, multimode fiber exhibits higher
      thresholds for non-linear effects, a larger capture fraction of Rayleigh
      backscattered light, and the potential to avoid signal fading by detecting many
      spatial modes in parallel. Previous multimode fiber based OTDR sensors discarded
      most of the backscattered light and thus failed to take advantage of these noise
      reducing factors. Here, we show that by performing off-axis holography with a
      high-speed camera, we can record the entire Rayleigh backscattered field,
      maximizing the detected light level and making the sensor immune to fading. The
      sensor exhibits a high degree of linearity, a minimum phase noise of -80 dB [rel.
      rad2/Hz], and 20 kHz bandwidth.

PMID- 30184959
TI  - Effect of growth temperature on the structural and optical properties of few
      layer hexagonal boron nitride by molecular beam epitaxy.
AB  - We have studied the epitaxy of few-layer hexagonal boron nitride (h-BN) by plasma
      assisted molecular beam epitaxy (MBE) using a low growth rate and nitrogen-rich
      condition. It has been determined that under such conditions, the growth
      temperature is the factor having the most significant impact on the structural
      and optical quality of the material. When grown at temperatures <1000  degrees C,
      the h-BN film is polycrystalline, and defect-related photoluminescence (PL)
      emission dominates. Epitaxial domains of exceptional crystalline quality are
      obtained at elevated substrate temperatures of ~1300  degrees C, which exhibit
      strong band-edge PL emission at ~220 nm and negligible defect-related emission at
      room temperature. Our atomistic calculations reveal that, even though the gap of
      h-BN is indirect, it luminesces as strongly as direct-gap materials.
      Experimentally, the luminescence intensity of such a few-layer h-BN sample is
      measured to be two orders of magnitude stronger than that of a 4-um thick
      commercially grown AlN template on sapphire, demonstrating the extraordinary
      potential of epitaxial h-BN for deep ultraviolet (UV) optoelectronics and quantum
      photonics.

PMID- 30184960
TI  - Efficient subpixel registration for polarization-modulated 3D imaging.
AB  - To implement real-time 3D reconstruction and displaying for polarization
      modulated 3D imaging lidar system, an efficient subpixel registration based on
      maximum principal component analysis (MPCA) is proposed in this paper. With which
      only the maximum principal component is estimated to identify non-integer
      translations in spatial domain while other principal components affected by noise
      are ignored. Consequently, robustness and stability of the subpixel registration
      is implemented in presence of noise, while computational complexity is reduced
      and memory size is saved simultaneously, especially when the image size is large.
      Both simulated and real polarization-modulated images are used to verify the
      proposed method. Simulation results show that 0.01 pixels of the registration
      accuracy are implemented; meanwhile, experimental results show that the proposed
      method can effectively reconstruct the depth image in real world application.

PMID- 30184961
TI  - Pulse compression to one-tenth of phonon lifetime using quasi-steady-state
      stimulated Brillouin scattering.
AB  - A new stimulated Brillouin scattering (SBS) compression mechanism, quasi-steady
      state SBS compression, in which the compression limit is one-tenth of the phonon
      lifetime with a high energy efficiency, is proposed and practically realized in
      this study. The feasibility of this approach is demonstrated experimentally, in
      which a compression of 0.36tauB with an energy efficiency of 65% is achieved in a
      3M Fluorinert Electronic Liquid FC-3283 and a compression output of 0.12tauB
      (near-compression-limited) with an energy efficiency above 40% is obtained in
      acetone when the phonon lifetime to leading-edge to ratio is greater than 10.
      This ratio is identified experimentally as the key parameter in quasi-steady
      state SBS compression. This work provides a practical approach to reliably
      generating one-tenth-phonon-lifetime pulses by quasi-steady-state SBS
      compression.

PMID- 30184962
TI  - Self-consistent dielectric constant determination for monolayer WSe2.
AB  - Frequency-dependent dielectric constant dispersion of monolayer WSe2,
      epsilon(omega)=epsilon1(omega)+i epsilon2(omega), was obtained from
      simultaneously measured transmittance and reflectance spectra. Optical
      transitions of the trion as well as A-, B-, and C-excitons are clearly resolved
      in the  epsilon2 spectrum. A consistent Kramers-Kronig transformation between the
      epsilon1 and  epsilon2 spectra support the validity of the applied analysis. It
      is found that the A- and B-exciton splitting in the case of the double-layer WSe2
      can be attributed to the spin-orbit coupling, which is larger than that in the
      monolayer WSe2. In addition, the temperature-induced evolution of the A-exciton
      energy and its width are explained by model equations with electron-phonon
      interactions.

PMID- 30184963
TI  - Detection and compensation of power imbalance, modulation strength, and bias
      drift in coherent IQ transmitter through digital filter.
AB  - A novel method to simultaneously detect power imbalance, modulation strength, and
      bias drift of coherent IQ transmitter during the initial power-up is presented.
      This is achieved by sweeping gain scaling factor of finite impulse filter in a
      digital domain and monitoring the combined output power. Furthermore, by
      dithering gain scaling factor of finite impulse filter, the power imbalance is
      measured with live traffic. Those impairments can be compensated accordingly. For
      example, the power imbalance is compensated through adjustment of gain setting of
      a radio frequency amplifier. This novel method works for multiple channels over C
      band, and the built-in photodiode of coherent transmitter provides sufficient
      accuracy.

PMID- 30184964
TI  - Propagation characteristics of partially coherent circular Airy beams.
AB  - The abruptly autofocusing properties of partially coherent circular Airy beam
      (CAB) with different spatial coherent length are theoretically investigated in
      this paper. It is found that, as spatial coherent length decreases, the size of
      the focal spot would increase and the focal intensity would decrease. But the
      abruptly autofocusing property for partially coherent CAB is still quite obvious,
      when comparing with the common partially coherent Gaussian beam under the same
      conditions; and its autofocusing position is less easily influenced by coherence.
      The influences of initial radius r0 and decaying parameter a on the autofocusing
      property have also been investigated in the end.

PMID- 30184965
TI  - Orthonormalization method in ghost imaging.
AB  - Ghost imaging system requires a large number of samples to reconstruct the
      object. Computational ghost imaging can use well-designed pre-modulated
      orthogonal patterns to reduce the requirement of sampling number and increase the
      imaging quality, while the rotating ground glass (RGG) scheme cannot. Instead of
      the pre-modulation method, a post-processing method using Gram-Schmidt process to
      orthonormalize the patterns in a RGG scheme is introduced. Reconstructed ghost
      image after the Gram-Schmidt process (SGI) are tested using the quality
      indicators such as the Contrast-to-Noise (CNR), the Peak Signal to Noise Ratio
      (PSNR), the Correlation Coefficient (CC) and reducing the Mean Square Error
      (MSE). Simulation results show that this method has obvious advantage on
      enhancing the efficiency of image acquisition, and the sampling number
      requirement drops from several thousands to a few hundreds in ideal condition.
      However, in actual system with noise, the image quality from SGI declines in
      large sampling number, for noise and errors accumulate in the orthonormalization
      process. So an improved Group SGI method is then developed to avoid this error
      accumulation, which behaves effectively in reconstructing the image from
      experimental data and show good performances in large sampling number too. Since
      this method do not change the relationship between the reference patterns and the
      bucket values, it can easily combine with most of reconstruction algorithms and
      improve their reconstruction efficiency.

PMID- 30184966
TI  - Correlation between photoluminescence and morphology for single layer self
      assembled InGaAs/GaAs quantum dots.
AB  - Single layer self-assembled InGaAs quantum dots (QDs) are manipulated by using
      different arsenic species on GaAs (100) surface. The As4 molecules are
      experimentally observed to be more promising than As2 to promote the formation of
      one-dimensionally-aligned QD-chain arrays. The lateral alignment of QDs and the
      corresponding formation of dot chains are explained by the anisotropic surface
      kinetics in combination with the different reactivities of the two molecules with
      bonding sites on the GaAs (100) surface. Photoluminescence (PL) measurements
      demonstrate that the spectra of the QD-chains broaden to higher energy and
      increases in intensity with increasing excitation laser power. The PL band of the
      QD-chains also exhibits a 9 meV reduction in linewidth as temperature increases
      starting from 8 K. These observations confirm an efficient lateral coupling
      between neighboring QDs and thereafter polarized QD emission, whereas the
      randomly distributed QDs grown with As2 show no preferential polarization. Such
      QD-chains exhibiting anisotropic properties have the potential for nanophotonics
      applications like electro-optic modulators with very low drive voltage and ultra
      wide bandwidth operation.

PMID- 30184967
TI  - Subwavelength resolution Fourier ptychography with hemispherical digital
      condensers.
AB  - Fourier ptychography (FP) is a promising computational imaging technique that
      overcomes the physical space-bandwidth product (SBP) limit of a conventional
      microscope by applying angular-varied illuminations. However, to date, the
      effective imaging numerical aperture (NA) achievable with a commercial LED board
      is still limited to the range of 0.3-0.7 with a 4 * /0.1NA objective due to the
      geometric constraint with the declined illumination intensities and attenuated
      signal-to-noise ratio (SNR). Thus the highest achievable half-pitch resolution is
      usually constrained between 500-1000 nm, which cannot meet the requirements of
      high-resolution biomedical imaging applications. Although it is possible to
      improve the resolution by using a high-NA objective lens, the FP approach is less
      appealing as the decrease of field-of-view (FOV) will far exceed the improvement
      of spatial resolution in this case. In this paper, we initially present a
      subwavelength resolution Fourier ptychography (SRFP) platform with a
      hemispherical digital condenser to provide high-angle programmable plane-wave
      illuminations of 0.95NA, attaining a 4 * /0.1NA objective with the final
      effective imaging performance of 1.05NA at a half-pitch resolution of 244 nm with
      the incident wavelength of 465 nm across a wide FOV of 14.60 mm2, corresponding
      to a SBP of 245 megapixels. Our work provides an essential step of FP towards
      high-throughput imaging applications.

PMID- 30184968
TI  - Light extraction enhancement and directional control of scintillator by using
      microlens arrays.
AB  - The total internal reflection restricts light extraction efficiency of
      scintillator, leading to reduced detection efficiency and signal-to-noise ratio
      in the field of scintillator-based radiation detection system. This research
      presents the method of applying microlens arrays to improve the light extraction
      efficiency as well as achieve directional control of emission for scintillators.
      For BGO (Bi4Ge3O12) scintillator covered with PMMA (polymethyl-methacrylate)
      hemispherical microlens array, the 2.59-fold in particular angle (thetaem = 45
      degrees ) and overall 1.94-fold angle-integrated enhancement ratios have been
      obtained. Furthermore, we analyze and optimize some parameters of microlens
      arrays such as the packing arrangement, duty ratio, size, refractive index, and
      shape. As a result, when the refractive index of microlens is slightly larger
      than that of scintillator, a maximum 6.23-fold angle-integrated enhancements can
      be achieved. It can be concluded that the microlens array covered on scintillator
      has considerable value for practical applications on radiation detection.

PMID- 30184969
TI  - Quantitative theory of X-ray interferometers based on dual phase grating: Fringe
      period and visibility.
AB  - In most of grating x-ray interferometry one needs an absorbing grating as the
      analyzer to measure high-resolution interference fringes. Dual phase grating
      interferometry is a technique to get rid of the absorbing grating for radiation
      dose reduction. The authors present a quantitative theory of dual grating x-ray
      interferometry. The theory elucidates the fringe formation mechanism. The derived
      formulas of fringe period and fringe visibility provide useful tools for design
      optimization of dual phase grating interferometers.

PMID- 30184970
TI  - High speed magneto-optical imaging system to investigate motion characteristics
      of arc plasma in enclosed chamber.
AB  - Arc plasmas are common and important phenomena, which have been widely used in
      scientific research and industrial fields. It is a non-intrusive way to
      understand the dynamic characteristics of arc plasma by measuring magnetic field
      distribution and applying inverse method. Aiming to investigate the motion
      characteristics of arc plasma, a high-speed magneto-optical imaging system was
      developed, which mainly consists of a laser-driven light source, achromatic
      collimator, beam expander, polarized beam splitter, analyzer and high-speed
      camera. The calibration experiment of the system, which was conducted using a
      Faraday indicator with a Verdet constant of -96 rad/(T.m)@632.8 nm and Helmholtz
      coils, shows its magnetic sensitivity reaches 1 mT, spatial resolution is about
      500MUm, temporal resolution is 100MUs as for a circular measuring area of 42 mm
      in diameter. The arcing experimental results also demonstrate that the developed
      system can obtain the 2D magnetic field distribution in real time with relatively
      high spatial and temporal resolution and reasonable magnetic sensitivity. It also
      provides an effective method to study the motion characteristics of arc plasma
      inside of an enclosed chamber.

PMID- 30184971
TI  - Coexisting frequency combs spaced by an octave in a monolithic quantum cascade
      laser.
AB  - Quantum cascade lasers are proving to be instrumental in the development of
      compact frequency comb sources at mid-infrared and terahertz frequencies. Here we
      demonstrate a heterogeneous terahertz quantum cascade laser with two active
      regions spaced exactly by one octave. Both active regions are based on a four
      quantum well laser design and they emit a combined 3 mW peak power at 15 K in
      pulsed mode. The two central frequencies are 2.3 THz (bandwidth 300 GHz) and 4.6
      THz (bandwidth 270 GHz). The structure is engineered in a way that allows
      simultaneous operation of the two active regions in the comb regime, serving as a
      double comb source as well as a test bench structure for all waveguide internal
      self-referencing techniques. Narrow RF beatnotes (~ 15 kHz) are recorded showing
      the simultaneous operation of the two combs, whose free-running coherence
      properties are investigated by means of beatnote spectroscopy performed both with
      an external detector and via self-mixing. Comb operation in a highly dispersive
      region (4.6 THz) relying only on gain bandwidth engineering shows the potential
      for broad spectral coverage with compact comb sources.

PMID- 30184972
TI  - Planar dielectric cylindrical lens at 800 nm and the role of fabrication
      imperfections.
AB  - Conventional optical components have been proposed to realize high-quality line
      focusing with uniform intensity distribution such as cylindrical lenses,
      segmented wedge-arrays, or a combination of prisms and spherical mirrors.
      Numerous factors such as the manufacturing tolerances or the need for precise
      alignment of conventional lenses cause wave front aberrations that impact the
      performance of optical systems. These aforementioned limitations affect the
      uniformity of the intensity distribution and the intercept factor of lenses.
      Here, we experimentally demonstrate an integrable planar dielectric cylindrical
      lens made of titanium dioxide for uniform line focusing and discuss the
      sensitivity of its performance to fabrication imperfections originating from non
      ideal geometrical parameters. The lens has a numerical aperture of 0.247, an
      intercept factor of 0.85, and an efficiency of 79% at 800 nm.

PMID- 30184973
TI  - Dual-polarized reflectarray for generating dual beams with two different orbital
      angular momentum modes based on independent feeds in C- and X-bands.
AB  - In this paper, a dual-band dual-polarized reflectarray for generating dual beams
      with respect to carrying two different orbital angular momentum (OAM) topological
      charges operating in the C-band in horizontal polarization and in the X-band in
      vertical polarization is proposed, with two separate horns performing on the two
      proposed bands as the feeding. The proposed reflectarray consists of two band
      reflective element cells operating in two orthogonal directions. Owing to the two
      composing elements orthogonally interleaved on the reflectarray surface, the
      corresponding phase compensation performance in one band can be slightly affected
      by the elemental resonance in another band; thus, the degree of the coupling
      between the elements with different-band operations can be neglected, resulting
      in fairly independent phase compensation. In other words, the desired OAM
      generation reflectarray, to some extent, can be developed based on two different
      frequency band OAM reflectarrays at the same aperture. In addition, simulations
      and measurements strongly suggest the feasibility and the validity of the
      approach, which provides a solid foundation for the application of multi-band
      reflectarrays to the multi-OAM-mode generation.

PMID- 30184974
TI  - Nonlinear propagation and quasi self-confinement of light in plasmonic resonant
      media.
AB  - We study nonlinear propagation of light in colloidal suspension of metallic
      nanoparticles, in the regime of particles surface plasmon resonance. We show that
      the propagation exhibits features typical for purely defocusing media and the
      observed spatial confinement is not a real self-trapping, as for solitons, but
      rather than is caused by the phase modulation of the beam via nonlocal defocusing
      nonlinearity. We also show that the light-induced refractive index change in the
      suspension leads to stabilization of structured light beams. In particular, we
      demonstrate a stable nonlinear propagation of bright ring beams with complex
      states of polarization, including practically important radial and azimuthal
      states.

PMID- 30184975
TI  - Efficient enhancement of bismuth near infrared luminescence by the co-doping of
      tantalum in GYAP crystal.
AB  - Bi/Ta double doped Gd0.1Y0.9AlO3 (Bi/Ta:GYAP) near-infrared (NIR) laser crystal
      was successfully grown. The codoping of Ta5+ was demonstrated to effectively
      enhance the NIR fluorescence emission in Bi/Ta:GYAP crystal for the first time.
      The introduced Ta5+ ion can induce the change of valence states from Bi3+ to Bi+
      based on the charge compensation mechanism, bringing about the enhanced NIR
      fluorescence emission. The three NIR fluorescence emission peaks centering at
      1005, 1195, and 1280 nm were ascribed to three different Bi+ active centers in
      Bi/Ta:GYAP crystal. These results suggest that the Bi/Ta:GYAP crystal may have
      potential applications in NIR broadband lasers.

PMID- 30184976
TI  - Flat-top optical resonance in a single-ring resonator based on manipulation of
      fast- and slow-light effects.
AB  - Optical single-ring resonance inherently generates Lorentzian-shape magnitude and
      group-delay responses, leading to critical performance limitation in photonics,
      cavity quantum electrodynamics, cavity optomechanics, and atomic and optical
      physics. Here, we propose a new type of microresonator that stimulates flat-top
      resonance in a single-ring cavity. By manipulating the fast and slow light
      effects in the microresonator, the flat-top group delay can be tuned with an
      ignorable magnitude variation. In addition, the bandpass response can be switched
      to a notch, which can enable function-reconfigurable photonic integrated circuits
      (PICs) without a physical change in the architecture. Our demonstration provides
      the possibility of developing microresonator-based PICs with unprecedented high
      flexibility and capacity.

PMID- 30184977
TI  - Strong optical force and its confinement applications based on heterogeneous
      phosphorene pairs.
AB  - We study the plasmonic properties of face-to-face phosphorene pairs, including
      their optical constraints and optical gradient forces. The symmetric and anti
      symmetric plasmonic modes occur due to the strong anisotropic dispersion of
      phosphorene. Compared with the anti-symmetric mode, the symmetric mode has a
      stronger optical constraint and much larger gradient force. Especially, the
      optical constraint of the symmetric mode can even reach as high as 96% when the
      two phosphorene layers are along the armchair and zigzag direction respectively.
      We also propose a scheme of an ultra-small phase shifter using phosphorene-based
      photonic devices.

PMID- 30184978
TI  - Sparse view cone beam X-ray luminescence tomography based on truncated singular
      value decomposition.
AB  - Cone beam X-ray luminescence computed tomography (CB-XLCT) has been proposed as a
      promising hybrid imaging technique. Though it has the advantage of fast imaging,
      the inverse problem of CB-XLCT is seriously ill-conditioned, making the image
      quality quite poor, especially for imaging multi-targets. To achieve fast imaging
      of multi-targets, which is essential for in vivo applications, a truncated
      singular value decomposition (TSVD) based sparse view CB-XLCT reconstruction
      method is proposed in this study. With the weight matrix of the CB-XLCT system
      being converted to orthogonal by TSVD, the compressed sensing (CS) based L1-norm
      method could be applied for fast reconstruction from fewer projection views.
      Numerical simulations and phantom experiments demonstrate that by using the
      proposed method, two targets with different edge-to-edge distances (EEDs) could
      be resolved effectively. It indicates that the proposed method could improve the
      imaging quality of multi-targets significantly in terms of localization accuracy,
      target shape, image contrast, and spatial resolution, when compared with
      conventional methods.

PMID- 30184979
TI  - Polarization-controlled generation of Airy plasmons.
AB  - Plasmonic metasurfaces have shown great potential to generate Airy plasmons on a
      metal surface, but the building block of metasurfaces in these works is purposely
      designed to operate under limited polarization states for the incident light.
      Here, it is shown that paired nanoslit resonators on a metal surface can provide
      Airy phase distributions under different polarization incidences. We demonstrate
      that Airy plasmons can be generated under x-, y-, left-handed circular, and right
      handed circular polarization incidences by adjusting the orientation angles of
      the paired nanoslit resonators. Analogous to previous proposals, Airy plasmons
      exhibit remarkable non-diffraction, self-healing, and autofocusing properties in
      the present configuration. The presented design scheme suggests promising
      applications in polarization-controlled plasmonic circuits and surface optical
      manipulation.

PMID- 30184980
TI  - Photonic properties of heliconical liquid crystals.
AB  - Periodic birefringence is today extensively explored as an interesting route for
      controlling the flow of light. Distinctly, complex fluids with periodic
      modulations of birefringence can perform as photonic crystals, with the main
      examples being cholesteric and blue phases birefringent profiles. Here we
      demonstrate the characteristics of light propagation in heliconical liquid
      crystal and demonstrate their tunable optical and photonic properties,
      specifically as one-dimensional photonic crystals, in the regime of heliconical
      pitch comparable to the wavelength of light. Using a combination of frequency-
      and time-domain simulations, we show the existence and properties of the photonic
      band gap, as determined by the relative handedness of the polarization of light
      and the heliconical structure. We calculate photonic eigenmodes of the light and
      find the emergence of electric field component along the propagation axis of
      light, for both left- and right-handed polarization of light, which in turn
      results in strongly spatially varying Poynting vector that exhibits circular-like
      and four-leaf-clover-like patterns. As this variation of the Poynting vector is
      tunable with various material parameters and external (electric) fields,
      heliconical birefringence photonic crystals show interesting potential for use in
      tunable photonic applications, such as complex modulation of light beams.

PMID- 30184981
TI  - Two-dimensional stitching interferometry based on tilt measurement.
AB  - In this paper, a two-dimensional stitching interferometry system using two
      tiltmeters is proposed. During the scanning and the measurement, one tiltmeter
      stays with the interferometer and the other one is attached to the translation
      stage where the surface under test is placed. The differences of the x- and y
      tilt readings between these two tiltmeters are recorded as the relative tilt
      between interferometer and surface under test. The relative tilt in both x- and y
      directions are used to correct the surface tip/tilt of each subset, and then the
      piston is adjusted to get the final stitching surface map. As an example, a
      stitching result of a 125mm-long mirror surface is presented. The repeatability
      of our current stitching system is about 1.48 nm RMS. The stitching result is
      compared to the result of a one-dimensional angular-measurement-based stitching
      method to discuss the merits and limitation of the proposed method.

PMID- 30184982
TI  - Fabrication of a high-quality axicon by femtosecond laser ablation and CO2 laser
      polishing for quasi-Bessel beam generation.
AB  - We report on the fabrication of an axicon by applying a two-step manufacturing
      process including a 1030 nm femtosecond and a 10.6 um CO2 laser. First, the pre
      defined axicon geometry is generated by high-precision femtosecond layer-by-layer
      ablation. In order to meet high surface quality requirements, inevitable
      stipulated for optical use, the surface of the thus structured axicon is
      smoothened by a subsequent CO2 laser polishing process. The finalized axicon
      fulfills optical quality as the surface roughness Ra is significantly reduced
      from 0.56 um to 34 nm. For the evaluation of the optical quality, the axicon is
      placed in a measurement setup including the femtosecond laser. Comparison between
      the calculated Bessel beam for an ideal axicon and the quasi-Bessel beam
      generated and measured by the fabricated axicon reveals excellent agreement,
      verifying our precise manufacturing method.

PMID- 30184983
TI  - Multimode-pumped Raman amplification of a higher order mode in a large mode area
      fiber.
AB  - We report the first demonstration of Raman amplification in a fiber of a single
      Bessel-like higher order mode using a multimode pump source. We amplify the LP08
      mode with a 559-um2 effective mode area at a signal wavelength of 1115 nm in a
      pure-silica-core step-index fiber. A maximum of 18 dB average power gain is
      achieved in a 9-m long gain fiber, with output pulse energy of 115 uJ. The Raman
      pump source comprises a pulsed 1060 nm ytterbium-doped fiber amplifier with V
      value ~30, which is matched to the Raman gain fiber. The pump depletion as
      averaged over the signal pulses reaches 36.7%. The conversion of power from the
      multimode pump into the signal mode demonstrates the potential for efficient
      brightness enhancement with low amplification-induced signal mode purity
      degradation.

PMID- 30184984
TI  - Free space optical secret key agreement.
AB  - Free space optical (FSO) communications are enabling high-speed global wireless
      networks. Thanks to the highly directional nature of laser beam, they also yield
      a greater security advantage over radio frequency counterparts. When combined
      with a scheme of secret key agreement (SKA), FSO-SKA can establish at high speed
      a symmetric secret key which cannot be decrypted even by unbounded computer
      resources. Although there have been many theoretical studies on SKA, experimental
      investigations have been quite lacking, especially on quantifying eavesdropping
      risks and secret key rates in realistic environment. Here, we report the first
      full-field implementations of FSO-SKA in a 7.8-km terrestrial link with a probing
      station, enabling the estimation of eavesdropping risks. We attain the final key
      rates from 100 kbps to 7.77 Mbps under various atmospheric and beaming conditions
      even with total losses of 55dB or higher, in which known quantum key distribution
      schemes attain impractically low key rates.

PMID- 30184985
TI  - Self-error-corrected hyperparallel photonic quantum computation working with both
      the polarization and the spatial-mode degrees of freedom.
AB  - Usually, the hyperparallel quantum computation can speed up quantum computing,
      reduce the quantum resource consumed largely, resist to noise, and simplify the
      storage of quantum information. Here, we present the first scheme for the self
      error-corrected hyperparallel photonic quantum computation working with both the
      polarization and the spatial-mode degrees of freedom of photon systems
      simultaneously. It can prevent bit-flip errors from happening with an imperfect
      nonlinear interaction in the nearly realistic condition. We give the way to
      design the universal hyperparallel photonic quantum controlled-NOT (CNOT) gate on
      a two-photon system, resorting to the nonlinear interaction between the
      circularly polarized photon and the electron spin in the quantum dot in a double
      sided microcavity system, by taking the imperfect interaction in the nearly
      realistic condition into account. Its self-error-corrected pattern prevents the
      bit-flip errors from happening in the hyperparallel quantum CNOT gate, guarantees
      the robust fidelity, and relaxes the requirement for its experiment. Meanwhile,
      this scheme works in a failure-heralded way. Also, we generalize this approach to
      achieve the self-error-corrected hyperparallel quantum CNOTN gate working on a
      multiple-photon system. These good features make this scheme more useful in the
      photonic quantum computation and quantum communication in the future.

PMID- 30184987
TI  - Nonellipsometric electro-optic sampling of terahertz waves in GaAs.
AB  - We report efficient high-resolution electro-optic sampling detection of broadband
      terahertz radiation by measuring direct intensity modulation of a femtosecond
      fiber laser beam induced by terahertz field in a 1-cm thick GaAs crystal.

PMID- 30184986
TI  - Construction of optimized Au@Ag core-shell nanorods for ultralow SERS detection
      of antibiotic levofloxacin molecules.
AB  - The abuse of antibiotics in animal husbandry has been regarded as a daunting
      public health risk, facilitating the emergence and spread of resistant pathogens
      to humans. Herein, bimetallic Au@Ag core-shell nanorods (NRs) with precise,
      controllable Ag shell-thickness (2.1~14.1 nm) were fabricated and developed for
      ultralow detection of levofloxacin molecules using surface enhanced Raman
      scattering spectroscopy (SERS). We found that the Au@Ag NRs with 7.3 nm Ag shell
      thickness provided maximized SERS activity in comparison with other as-prepared
      nanosubstrates in this paper. The detection limit of levofloxacin molecules was
      achieved at a nanomole (nM) level of 0.37 ng/L (10-9 M), providing ultrasensitive
      assessment of antibiotics in natural ecosystems.

PMID- 30184988
TI  - 5D hyperspectral imaging: fast and accurate measurement of surface shape and
      spectral characteristics using structured light.
AB  - Measuring the shape (coordinates x, y, z ) and spectral characteristics
      (wavelength-dependent reflectance R (lambdai)) of macroscopic objects as a
      function of time (t) is of great interest in areas such as medical imaging,
      precision agriculture, or optical sorting. Here, we present an approach that
      allows to determine all these quantities with high resolution and accuracy,
      enabling measurement in five dimensions. We call this approach 5D hyperspectral
      imaging. We describe the design and implementation of a 5D sensor operating in
      the visible to near-infrared spectral range, which provides excellent spatial and
      spectral resolution, great depth accuracy, and high frame rates. The results of
      various experiments strongly indicate the great benefit of the new technology.

PMID- 30184989
TI  - The morphology of a harpacticoid copepod gut: A review and synthesis.
AB  - The digestive tract of a harpacticoid copepod, Tigriopus californicus (Baker),
      was studied by using techniques of light and electron microscopy. Four cell types
      could be distinguished: type 1, an embryonic cell which will replace cells worn
      away or lost during secretion; type 2, a cell which synthesizes and secretes
      proteins and also plays a role in lipid absorption; and types 3 and 4, two cell
      types which absorb lipids. From the abundance of each cell type, the length of
      microvilli, the development of basal plasma membrane (PM), and luminal
      projections, the following conclusions were made. (1) The midgut caecum absorbs
      digested nutrients. (2) The anterior midgut absorbs nutrients and more
      importantly functions in merocrine and exocrine secretion. The presence of
      concretions in cell types 2 and 3 in the anterior midgut suggests that these
      tissues contribute in excretion, and in water and/or ion regulation. (3) The
      posterior midgut absorbs nutrients and contributes some holocrine secretion.

PMID- 30184990
TI  - The auditory region of dermoptera: Morphology and function relative to other
      living mammals.
AB  - The dermopteran basicranium combines a primitively constructed and oriented
      auditory bulla formed by ectotympanic, rostral entotympanic, and tubal cartilage
      with derived features of the middle ear transformer and internal carotid
      circulation. Living dermopterans possess a primitive eutherian auditory region
      that has been structurally modified to perceive a lower frequency sound spectrum
      than probably was utilized by ancestral Mesozoic therians. Perception of the low
      to midfrequency range is enhanced in Dermoptera by reducing stiffness in the
      mechanical transformer while maintaining low mass of the component parts.
      Stiffness has been reduced by (1) development of an epitympanic sinus about four
      times the volume of the middle ear cavity proper, (2) detachment of the anterior
      process of the malleus from the ectotympanic, and (3) by delicate suspension of
      the ear ossicles within the middle ear. We apply to dermopterans a measure of
      hearing efficiency derived from recent functional studies of the mammalian middle
      ear that regards the middle ear mechanism as an impedance matching transformer.
      Calculation of the impedance transformer ratio for Dermoptera suggests that these
      mammals are relatively efficient in comparison to other eutherians in their
      ability to match the impedance of cochlear fluids to that of air at the eardrum.
      Dermopterans theoretically are capable of using over 90% of incident sound energy
      striking the eardrum at the resonant or natural frequency. Mechanical impedance
      of the middle ear transformer exerts a minimal influence on hearing efficiency
      due to low mass, little stiffness, and little frictional resistance. Analysis of
      measurements of the middle ear transformer published by Gerald Fleischer and
      integration of these data with current theory on the peripheral hearing mechanism
      in mammals allow us to propose a model that describes the structural and
      functional evolution of the mammalian middle ear transformer. Structural changes
      appear to be correlated with alteration in function from primitive small mammals
      with stiff middle ear transformers and high frequency dominated hearing to
      mammals with a wider range in body size with more mobile middle ear transformers
      and a greater range of frequency perception, often including improved sensitivity
      to lower frequencies. Mammals employ different anatomical strategies in
      attainment of increased hearing efficiency and sensitivity. Efficiency is
      improved by adjustment of lever and areal ratios of the middle ear transformer to
      achieve an optimum impedance match of external air and cochlear fluids.
      Sensitivity over a broad frequency spectrum is attained by minimizing mass,
      stiffness, and frictional resistance of the transformer. The morphology of the
      auditory region of both living and fossil mammals seems explicable in terms of
      selection pressure directed toward these ends.

PMID- 30184991
TI  - Structural modulation of the surface and cytoplasm of oocytes during
      vitellogenesis in the lobster, Homarus americanus. An electron microscope-protein
      tracer study.
AB  - The present investigation describes the ultrastructural changes which occur at
      the surface and in the cytoplasm of developing oocytes of the lobster, Homarus
      americanus, during vitellogenesis. The immature oocytes showed no surface
      specializations of the oolemma and no pinocytotic activity was observed.
      Horseradish peroxidase (HRP) tracer studies showed penetration of the tracer into
      the perivitelline space, but no uptake by the oocytes. The surfaces of oocytes
      examined during vitellogenesis, when yolk protein accumulation was maximal,
      exhibited numerous microvilli that projected into the perivitelline space, often
      appearing to be embedded in the follicular cell mass. In addition, the plasma
      membrane of vitellogenic oocytes contained many pinocytotic pits frequently
      situated at the bases of microvilli. The perivitelline space was engorged with
      electrondense material which appeared similar to that contained in pinocytotic
      structures of the oocytes. Vitellogenic oocytes incubated in HRP showed uptake of
      tracer reaction product by the coated pits and vesicles of the oolemma.
      Aggregation and subsequent fusion of these vesicles into large multivesicular
      bodies of ingested material were also observed in vitellogenic oocytes. Animals
      artificially induced to undergo vitellogenesis exhibited modulations of oocyte
      ultrastructure similar to those of normal vitellogenesis, notably, pinocytotic
      incorporation of extra-oocytic material and hypertrophy of oocyte surface
      microvilli. This study supports the hypothesis for a dual source of yolk protein
      in the American lobster.

PMID- 30184992
TI  - The functions of the lumbar spine during stepping in the cat.
AB  - To examine the functional roles played by the lumbar spine during overground
      stepping, seven adult cats were run in electromyographic (EMG) experiments.
      Recordings were made bilaterally from mm. iliocostalis, longissimus dorsi and
      multifidus at a single vertebral level (L3 ) and from m. rectus abdominis.
      Stepping movements were monitored synchronously either by videotape or by high
      speed cinematography. During alternate use of the hindlimbs (walking and
      trotting), both epaxial and abdominal muscles were active bilaterally and
      biphasically. During in-phase use of the hindlimbs (galloping and half-bounding),
      single bursts of activity were observed. Phasic bursts of activity in rectus
      abdominus were reciprocal to those of epaxial muscles. Second bursts of activity
      in either group were noted infrequently. Recordings from the same back muscle at
      several vertebral levels indicated little difference from these patterns.
      Movements of the lumbar spine during galloping and half-bounding steps, both
      angular and linear, are easily correlated with muscle activity patterns.
      Movements of the lumbar spine during walking and trotting show no particular
      pattern. Only small angular and linear movements are found. It is concluded that
      the lumbar spine contributes substantially to step length and limb speed during
      galloping and half-bounding steps and the epaxial and abdominal musculature may
      also act as elastic bodies. During walking and trotting steps, the epaxial
      muscles are proposed to act to stabilize the pelvic girdle to provide a firm base
      for limb muscles which arise on the pelvis and are synchronously active.

PMID- 30184993
TI  - The ultrastructure of the otolithic membrane and otolith in the juvenile
      mummichog, Fundulus heteroclitus.
AB  - The sagitta otolithic membrane of Fundulus heteroclitus consists of two different
      zones. A structured zone (gelatinous layer), which usually exhibits a reticulated
      or honeycomb-like architecture, is composed of tightly arranged fibrous material
      and covers only the sensory region of the macula. The gelatinous layer extends
      from the otolith surface to the tips of the sensory hairs, and probably functions
      primarily as a mechanoreceptor. The arrangement of this zone is closely
      associated with specific overlying structural features of the otolith surface and
      may also influence the pattern of mineral deposition to some degree. A
      nonstructured zone (subcupular meshwork) consists of fibers in very loose
      networks and covers both sensory and nonsensory regions of the macula. Over the
      sensory region, some of this fibrous material extends from the epithelial
      surface, through pores in the gelatinous layer, to the surface of the overlying
      otolith. In the nonsensory region, fibers of the subcupular meshwork are
      relatively more numerous and extend around the peripheral margin of the otolith.
      Evidence is presented which suggests that the fibrous material of the subcupular
      meshwork is incorporated into the otolith as an organic matrix constituent. New
      aspects on the ultrastructure of the otolith are presented and discussed.

PMID- 30184994
TI  - The distribution of monoamine oxidase and biogenic monoamines in the central
      nervous system of spiders (Arachnida: Araneida).
AB  - The distribution and activity patterns of monoamine oxidase and monoaminergic
      (formaldehyde-induced) fluorescence in the central nervous system of web-building
      and hunting spiders have been studied using histochemical methods. Enzyme
      activity occurred in the neuronal perikarya and in varying intensity in the
      structures of the neuropile mass, but only when dopamine, adrenaline, and
      noradrenaline were used as substrates. The optic centres of the spider brain
      normally exhibited relatively strong enzyme reactions when compared with the
      staining intensity of the rest of the nervous system. The neuronal cell bodies
      contained numerous granules of yellow-green fluorescence. Monoaminergic
      fluorescence of the neuropile was generally a weak green. The optic mases of the
      hunting spiders, the anterior bridge, several commissures of the ventral cord,
      and the neural lamellae showed a slightly higher fluorescence intensity and
      single fluorescing granules. The results obtained indicate the presence of
      catecholamines in the spider nervous system.

PMID- 30184995
TI  - The projection of neuroendocrine fibers (NCC I and II) in the brains of three
      orthopteroid insects.
AB  - Neuronal projections from neuroendocrine tracts (nervi corpori cordiaci I and II)
      in the brains of the locust (Schistocerca vaga), cricket (Acheta domesticus), and
      cockroach (Periplaneta americana) were studied using reconstructions of silver
      intensified cobalt chloride preparations. Collaterals from the NCC I in these
      species branch extensively in the dorsal protocerebral neuropile, anterior to the
      stalk of the corpora pedunculata and ventral to its calyces. Other fibers project
      from the NCC I bilaterally into the medial protocerebral neuropile, anterior to
      the central body, and posterior to the beta lobes. NCC II collaterals arborize in
      the medial, dorsal, and lateral protocerebral neuropile, their region of
      projection partially overlapping with that of the NCC I. Several NCC II fibers
      terminate in the superior arch of the central body in Acheta but not in the other
      two species. Tritocerebral cells filled through the NCC I branch in the medial
      tritocerebral neuropile in all three species, but most extensively in
      Schistocerca. No NCC fibers were seen to penetrate any part of the corpora
      pedunculata, protocerebral bridge, olfactory glomeruli, ocellar tracts, or optic
      lobes. These neuronal projections from the NCC I and II lie anterior to regions
      of branching of second-order ocellar fibers and thus provide no anatomical basis
      for direct ocellar input to neurosecretory cells, contrary to previous reports
      for orthopteroid species (Brousse-Gaury, '71a, b). However, interneurons filled
      from the optic lobes were found to terminate in the same region of dorsal
      protocerebral neuropile as NCC I and II fibers in Acheta, thus providing a
      possible pathway for optic input to the cerebral neuroendocrine system.

PMID- 30184996
TI  - The trunk musculature of caecilians (Amphibia: Gymnophiona).
AB  - Descriptions of the trunk musculature of six species representing sex genera and
      five families of caecilians reveal considerable variation, which may be useful in
      future systematic studies. The muscle units of the external muscular sheath (M.
      dorsalis trunci, M. subvertebralis) of caecilians are homologous with, and
      closely similar in position to, those of salamanders. The major difference in
      trunk musculature is the presence in caecilians of an additional muscle layer
      ventral to the M. subvertebralis. This muscle may be a neomorphic derivative from
      either the M. subvertebralis or the M. transversus. Unlike burrowing reptiles,
      which have ball-and-socket intervertebral joints, caecilians have retained the
      primitive amphicoelous centrum and compensate for stresses associated with
      burrowing by the presence of intercentral ligaments and interlocking basapophyses
      and subcentral keels. Association of Uraeotyphlus with the Ichthyophiidae and the
      validity of the Rhinatrematidae are supported by data from the trunk musculature.

PMID- 30184997
TI  - The morphology of dermal chromatophores in the infrared-reflecting glass-frog
      Centrolenella fleischmanni.
AB  - The morphology and organization of chromatophores in the neotropical glass-frog,
      Centrolenella fleischmanni (family Centrolenidae), were studied with both light
      and electron microscopes. Four types of pigment cells are described in the dorsal
      skin. The fine structure of two chromatophores corresponds to the typical
      amphibian xanthophore and iridophore; one is similar to the unusual melanophore
      found in phyllomedusine hylids; the fourth cell type is unlike any chromatophore
      previously described. Pigment granules in the unusual chromatophore are
      moderately electron-dense and have an irregular shape, suggesting a fluid
      composition. This pigment appears to be laid down in organelles similar in
      appearance to pterinosomes. The organization of pigment cells in this species
      differs from that of other green, leaf-sitting frogs in that there are few
      discrete groups resembling "dermal chromatophore units." It is suggested that the
      unusual new pigment cell contributes significantly to the overall green color of
      C. fleischmanni.

PMID- 30184998
TI  - Structure of the dermal scales in gymnophiona (Amphibia).
AB  - Histology and cytology of dermal scales of the gymnophionans Ichthyophis
      kohtaoensis and Hypogeophis rostratus reveal their structure and the nature of
      their mineralization. Dermal scales are small flat disks set in pockets in the
      transverse ridges of the skin. Each pocket contains several scales of various
      sizes. A ring of "hypomineralization" of varying diameter may occur on scales of
      a particular dermal pocket but bears no relation to the diameter of these scales.
      Three different layers form the scales and are seen on sections perpendicular to
      the surface. The cells of the basal layer lie deepest. Each of the two or three
      more superficial fibrous layers is composed of bundles of fibres that are
      oriented in parallel. The orientation varies among layers. The striation of the
      fiber scales has a periodicity comparable to that of the surrounding dermal
      fibers. Squamulae form a discontinuous layer on the scale surface and are the
      only mineralized part of the scale. The minerals are deposited both on the
      collagen fibers passing from the fibrous layers into the squamulae, and in the
      interfibrillar spaces. Spherical concretions, either isolated or coalescent,
      reaching up to 1 MUm, are found on the surface of the squamulae. The dermal
      scales of Gymnophiona present some analogies with those of evolved bony fishes.
      Their characteristics could make them an original model for the study of
      mineralization.

PMID- 30184999
TI  - [Some thoughts on the treatment strategy of thoracolumbar fracture].

PMID- 30185000
TI  - [Treatment of thoracolumbar fractures with three-dimensional reduction method and
      external fixation devices under analgesia].
AB  - OBJECTIVE: To compare the clinical effects between open reduction internal
      fixation and three-dimensional reduction with external fixation under analgesia
      in treating fresh thoracolumbar fractures, and explore the simple and effective
      method for thoracolumbar fractures. METHODS: The clinical data of 40 patients
      with thoracolumbar fractures who met the inclusion and exclusion criteria in the
      department of orthopaedics affiliated to Suzhou Hospital of Nanjing University of
      Chinese Medicine from February 2013 to August 2017 were retrospectively analyzed.
      According to therapeutic methods, the patients were devided into treatment group
      and control group, 20 cases in each group. Treatment group was treated by three
      dimensional reduction method and external fixation devices under analgesia, and
      control group was treated by open reduction and common spinal fixation system. In
      treatment group, there were 9 males and 11 females, aged from 26 to 68 years old
      with an average of (52.8+/-11.3) years; and in control group, there were 10 males
      and 10 females, aged from 26 to 64 years old with an average of(50.6+/-8.8)
      years. Anterior vertebral body compression(AVBC), Cobb angle and visual analogue
      scale(VAS) were measured and compared in two group. RESULTS: All 40 patients
      finished follow-up. The follow-up time in treatment group was 5 to 37 months with
      average of (16.1+/-8.8) months, in control group was 5 to 29 months with an
      average of(17.3+/-6.0) months. There was no significant difference between two
      groups(P>0.05). AVBC, Cobb angle, VAS score were obviously improved in all
      patients after treatment(P<0.05), but there were no significant difference
      between two groups(P>0.05). CONCLUSIONS: Clinical effect of two methods was
      similar in treating thoracolumbar fractures, but three-dimensional reduction and
      external fixation devices under analgesia has advantage of easy operation,
      smaller trauma and no need secondary surgery for removed internal fixation.

PMID- 30185001
TI  - [Treatment of thoracolumbar burst fractures with intelligent inflated reduction
      combined with percutaneous pedicle screw fixation].
AB  - OBJECTIVE: To evaluate the clinical outcome of intelligent inflated reduction
      combined with percutaneous pedicle screw fixation in treating thoracolumbar burst
      fractures. METHODS: The clinical data of 22 patients with thoracolumbar burst
      fractures of single segment treated from January 2013 to December 2015 were
      retrospectively analyzed. There were 12 males and 10 females, aged from 32 to 56
      years old with an average of (42.4+/-8.6) years. Self-made intelligent pneumatic
      reset instrument was applied to 22 cases under anaesthesia reduction, and then
      percutaneous pedicle screw fixation was performed. Clinical features were
      observed and the clinical effects were evaluated by VAS, ODI, kyphotic angle
      (Cobb angle) and the injured vertebral anterior border height before and after
      operation. RESULTS: All the patients were followed up from 1 to 2.5 years with an
      average of 18 months. All fractures obtained bone healing, no complications such
      as loosening, displacement, breakage of pedicle screw and kyphosis were found.
      Preoperative, 1 week postoperative, and final follow-up, VAS scores of lumbar
      pain were 7.82+/-0.85, 3.09+/-0.92, 1.05+/-0.72;ODI scores were 84.2+/-11.2,
      46.3+/-9.0, 12.2+/-4.3;Cobb angle were (16.3+/-5.4) degrees , (3.7+/-2.2) degrees
      , ( 5.5+/-2.6) degrees ; the injured vertebral anterior border heights were
      (59.5+/-7.8)%, (86.9+/-6.0)%, (83.5+/-5.5)%, respectively. There was significant
      differences in VAS, ODI scores between any two times(P<0.05). At 1 week
      postoperative and final follow-up, Cobb angle, injuried vertebral anterior border
      height were obviously improved (P<0.05), and there was no significant difference
      between postoperative 1 week and final follow-up (P>0.05). CONCLUSIONS: It is
      safe and feasible surgical technique that intelligent inflated reduction combined
      with percutaneous pedicle screw fixation for thoracolumbar burst fractures. It
      has advantage of little trauma, reliable fixation, and less complication, etc.
      Therefore, it is a better choice for single-segment thoracolumbar burst
      fractures.

PMID- 30185002
TI  - [Case-control study of pedicle screw fixation combined with vertebroplasty and
      injured vertebra pedicle fixation in treatment of osteoporotic thoracolumbar
      burst fractures].
AB  - OBJECTIVE: To compare the curative effect of short-segment pedicle screw fixation
      combined with vertebroplasty and injured vertebra pedicle fixation in treating
      osteoporotic thoracolumbar burst fractures. METHODS: A retrospective study was
      performed for 52 patients with thoracolumbar burst fractures from August 2010 to
      August 2015. Among them, 27 patients(group A) were treated with short-segment
      pedicle screw fixation combined with vertebroplasty, including 17 males and 10
      females, aged from 54 to 68 years old with an average of(61.01+/-5.41) years, 16
      cases were type A3 and 11 cases were type A4 according the new AO typing. Other
      25 patients (group B) were treated with short-segment pedicle screw fixation
      combined with injured vertebra pedicle fixation, including 12 males and 13
      females, aged from 55 to 66 years old with an average of (59.28+/-6.12) years, 18
      cases were type A3 and 7 cases were type A4 according the new AO typing.
      Operation time, intraoperative bleeding volume, complication, image data and
      clinical effect were compared between two groups. RESULTS: All the patients were
      followed up for 12 to 15 months with an average of (12.4+/-2.1)months. There was
      no significant difference in general data(including gender, age, injured site,
      preoperative VAS score, Cobb angle, injured vertebral anterior border height)
      between two groups. There was no significant differences in operation time,
      intraoperative bleeding volume between two groups. Preoperative, one week after
      operation and final follow-up, VAS scores were 5.2+/-0.5, 1.2+/-0.2, 0.8+/-0.1
      respectively in group A and 5.0+/-0.6, 2.5+/-0.4, 1.3+/-0.2 in group B; injured
      vertebral anterior border height were (49.4+/-6.8)%, ( 94.5+/-1.2)%, ( 94.1+/
      3.7)% respectively in group A and (48.2+/-7.0)%, ( 94.3+/-4.1)%, ( 90.0+/-2.3)%
      in group B;Cobb angles were (20.4+/-5.2)  degrees , (2.5+/-1.8)  degrees , (4.4+/
      1.7) degrees  respectively in group A and (19.8+/-6.8) degrees , (2.4+/-1.7)
      degrees , (7.0+/-1.2) degrees  in group B. At final follow-up, VAS, Cobb angle,
      injured vertebral anterior border height in two groups were obviously
      improved(P<0.05). Postoperative at 1 week and final follow-up, VAS score of group
      A was lower than that of group B(P<0.05);and there was no significant difference
      in Cobb angle between two groups(P>0.05); there was significant difference in
      injured vertebral anterior border height between two groups(P<0.05). The
      complication of internal fixation failure had 1 case in group A and 4 cases in
      group B. CONCLUSIONS: For the treatment of single osteoporotic thoracolumbar
      burst fractures, short-segment pedicle screw fixation combined with
      vertebroplasty is better than combined with injured vertebra pedicle fixation in
      clinical effect, it can relieve pain, maintain injured vertebral height and
      sagittal alinement, reduce the complications associated with internal fixation,
      and be worth spread in clinic.

PMID- 30185003
TI  - [Case control studies on unilateral or bilateral pedicle fixation at the level of
      fracture versus posterior fixation alone in the treatment of thoracolumbar
      fractures].
AB  - OBJECTIVE: To compare the clinical effects of three fixation methods at the level
      of fracture in treating thoracolumbar fractures. METHODS: From June 2012 to June
      2015, 67 patients with thoracolumbar fractures were treated with posterior short
      segment pedicle fixation. There were 45 males and 22 females, aged from 13 to 63
      years old with an average of 42.5 years. According to the methods of fixation at
      the level of fracture, the patients were divided into three groups. Group A
      included 26 patients treated by traditional posterior fixation alone. Group B
      included 19 patients treated by posterior fixation with unilateral pedicle
      fixation at the level of fracture. In group C, 22 patients were treated by
      posterior fixation with bilateral fracture-level screws. Radiological parameters
      and clinical outcomes were compared among the three groups. RESULTS: All the
      patients were followed up for 12 to 26 months with an average of 17.6 months. No
      complications such as incision infection, poor wound healing, internal fixation
      loosening and breakage were found. Preoperative, postoperative 1 week, and final
      follow-up, there were no significance differences among the three groups with
      respect to the relative height of the fractured vertebra (P>0.05). The sagittal
      Cobb angles among the three groups were similar preoperatively, and a week after
      operation (P>0.05). At latest follow-up, the sagittal Cobb angles and the
      correction loss of Cobb angle in group A were significantly larger than that of
      groups B and C (P<0.05), while there was no statistical difference between group
      B and group C (P>0.05). With respect to visual analogue scale (VAS) scores for
      back pain, the three groups were similar at preoperatively, a week after
      operation and the latest follow-up(P>0.05). CONCLUSIONS: Compared to traditional
      posterior fixation alone, unilateral or bilateral pedicle fixation at the level
      of fracture can significantly decrease the loss of correction in the middle-long
      term, and reduce the incidence of tardive kyphosis deformity and can obtain
      satisfactory radiological results and clinical outcomes with safe surgical
      procedures.

PMID- 30185004
TI  - [New external spinal skeletal fixation combined with percutaneous injury vertebra
      bone grafting for the treatment of two-segment thoracolumbar fractures].
AB  - OBJECTIVE: To investigate the clinical results of new external spinal skeletal
      fixation combined with percutaneous injury vertebra bone grafting in the
      treatment of two-segment thoracolumbar fractures without neural dysfunction.
      METHODS: The clinical data of 28 patients with two-segment thoracolumbar
      fractures without neural dysfunction treated from January 2013 to August 2015
      were retrospectively analyzed. There were 17 males and 11 females, with a mean
      age of(37.5+/-10.3) years (ranging from 19 to 55 years). According to fracture AO
      classification, all 28 cases were type A, including 2 cases of T10,11, 3 cases of
      T11,12, 9 cases of T12-L1, 4 cases of L1,2, 5 cases of L2,3, 4 cases of L3,4, 1
      case of L4,5. All 28 patients received treatment of new external spinal skeletal
      fixation and percutaneous injury vertebra bone grafting. Operation time,
      intraoperative bleeding and related complications were recorded. The informations
      of vertebral anterior border height percentage and bone fusion were observed by
      radiography before and after operation, before removed external fixation and
      final follow-up. Visual analogue scale(VAS) was used to evaluate the clinical
      effects. RESULTS: All the patients were followed up for 13 to 32 months with an
      average of (24.5+/-3.5) months. There was significant difference by the time of 3
      days postoperatively, before removed external fixation, final follow-up comparing
      with the preoperative in vertebral anterior border height percentage and VAS
      score(P<0.05). There was no significant difference in vertebral anterior border
      height percentage by the time of 3 days postoperatively, before removed external
      fixation comparing with final follow-up(P>0.05). While the VAS score showed a
      gradually declining trend, screw lossening ocurred in 2 cases and nail tracker
      infection occurred in 1 case after operation, and no other complications were
      found. CONCLUSIONS: New external spinal skeletal fixation and percutaneous injury
      vertebra bone grafting can got satisfactory clinical effect in treating two
      segment thoracolumbar fractures without neural dysfunction, which is an effective
      method of minimally invasive surgery.

PMID- 30185005
TI  - [Treatment of displacement-type lumbar intervertebral disc protrusion on L2-L5
      with percutaneous endoscopic interlaminar discectomy].
AB  - OBJECTIVE: To evaluate the operative characteristic, safety, clinical effect of
      percutaneous endoscopic interlaminar discectomy (PEID) in treating displacement
      type lumbar intervertebral disc protrusion on L2-L5. METHODS: Form November 2015
      to October 2016, 15 patients with displacement-type lumbar intervertebral disc
      protrusion were treated with percutaneous endoscopic interlaminar discectomy.
      There were 9 males and 6 females, aged from 19 to 63 years old with an average of
      42 years. All the patients with single-segment displacement-type lumbar
      intervertebral disc protrusion were diagnosed by clinical and iconography data,
      and complicated with low back pain and single lower limbs radioactivity pain.
      Lesion occurred in L4,5 of 8 cases, L3,4 of 4 cases, L2,3 of 3 cases. The
      patients were divided into 4 regions according to Lee standard (displaced nucleus
      pulposus location on spinal canal), I region was 2 cases, II region was 3 cases,
      III region was 5 cases, IV region was 5 cases.Preoperative, postoperative 3
      months, final follow-up, lumbago-leg pain and lumbar function were assessed by
      VAS, JOA scores;at final follow-up, MacNab was used to evaluate the clinical
      effect;postoperative 3 months, rechecked lumbar MRI to observe discectomy
      condition. RESULTS: All the operations were successfully complete under local
      anesthesia, and no complications such as injuries of nerve root and dural sac,
      postoperative hemorrhage, local infection were found. Operative time was 45 to 90
      min with an average of 54.8 min;and hospitalization time was 3 to 4 days with an
      average of 3 days. All 15 cases were followed up for 12 to 13 months with an
      average of 12.2 months, no recurrence was found. Preoperation, postoperative 3,
      12 months, VAS scores were 8.2+/-1.4, 3.0+/-0.6, 1.7+/-0.5, JOA scores were
      8.76+/-3.32, 23.61+/-2.14, 24.82+/-3.43, respectively. Postoperative VAS, JOA
      scores were obviously improved(P<0.05). According to MacNab standard to evaluate
      the clinical effect, 9 cases obtained excellent results, 5 good, 1 fair.
      CONCLUSIONS: PEID is a micro-trauma surgical method and has advantage of safe and
      effective in treating displacement-type lumbar intervertebral disc protrusion on
      L2-L5, but requires laminoplasty during operation, and under local anesthesia to
      operation maybe can induce neurostimulation.

PMID- 30185006
TI  - [Case control study on Mobi-C cervical artificial disc replacement and anterior
      cervical decompression MC+fusion for the treatment of cervical spondylosis].
AB  - OBJECTIVE: To compare the clinical effects and clinical indications between Mobi
      C cervical artificial disc replacement (CADR) and MC+ anterior cervical
      decompression and fusion(ACDF) in treating cervical spondylosis. METHODS: The
      clinical data of 100 patients with cervical spondylosis treated ACDF or CADR from
      June 2009 to June 2015 were retrospectively analyzed. There were 53 males and 47
      females, aged from 38 to 70 years old. Among them, 50 cases were treated by ACDF
      (ACDF group), follow-up time was for 22 to 42 months with an average of (32.24+/
      5.20) months;other 50 cases were treated by CADR (CADR group), follow-up time was
      for 23 to 48 months with an average of (30.40+/-5.66) months. Odom criterion was
      used to evaluate the clinical effects in two groups. JOA score, including sensory
      function, motor function and bladder function was used to assess the spinal cord
      function. Preoperative and postoperative responsible intervertebral space
      heights, cervical curvatures were compared by image data between two groups.
      RESULTS: All incisions obtained good healing and no serious complications were
      found. At final follow-up, 30 cases got excellent results, 12 good, 8 fair in
      ACDF group;and 34 cases got excellent results, 10 good, 6 fair in CADR
      group;there was no significant difference between two groups(u=4.000, P=0.827).
      At final follow-up, the scores of sensory function and motor function were
      obviously improved(P<0.05), and bladder function had not obviously recovered
      (P>0.05) in two groups;and CADR group in the scores of sensory function and motor
      function were obviously better than of ACDF group(P<0.05). There was no
      significant difference in preoperative intervertebral space height, cervical
      curvature between two groups, and at final follow-up both had different
      recovered. The recovery of CADR group was obviously better than of ACDF group.
      CONCLUSIONS: CADR can quickly recover normal action for patients and retains the
      movement. CADR has certain advantages in recovering cervical curvature,
      improveing sensory function and motor function, but it is not able to completely
      replace ACDF.

PMID- 30185007
TI  - [Clinical observation of percutaneous coblation nucleoplasty for the treatment of
      cervical spondylotic radiculopathy].
AB  - OBJECTIVE: To evaluate the clinical effects of percutaneous coblation
      nucleoplasty in treating cervical spondylotic radiculopathy and investigate its
      mechanism of action. METHODS: Form January 2015 to January 2017, 21 patients with
      cervical spondylotic radiculopathy were treated by percutaneous coblation
      nucleoplasty, including 8 males and 13 females with an average age of 49.6 years
      old ranging from 43 to 61 years old. The course of disease was for 1 to 6 months
      with a median age of 4 months. Three cases were single segment, 9 cases were
      double segments, 7 cases were three-segment, 2 cases were four-segment.
      Intervertebral disc pressure, VAS were compared before and after operation.
      Angular displacement(AD) and horizontal displacement(HD) were measured by image
      data and in order to evaluate the cervical stability. Modified MacNab criteria
      was used to assess clinical effects. RESULTS: All the patients were followed up
      from 1 to 12 months with an average of 8.6 months. Preoperative intervertebral
      disc pressure was (32.0+/-5.26) cmH2O and immediately after operation was (21.0+/
      7.18) cmH2O, there was statistical significance between before and after
      operation(P=0.003). Preoperative angular displacement and horizontal displacement
      was (3.85+/-1.26)  degrees  and (1.23+/-0.58) mm, six months after operation was
      (4.18+/-1.31)  degrees  and (1.69+/-0.46) mm, respectively. There was no
      statistical significance before and after operation(P>0.05). Preoperative VAS
      scores were 7.49+/-0.53, postoperative at 3 days, 3, 6 months were 3.51+/-0.49,
      2.63+/-0.61, 2.56+/-0.71, respectively, and postoperative obtained obvious
      improvement(P<0.05). According to modified MacNab criteria, 6 cases obtained
      excellent results, 7 good, 4 fair 3 poor at 3 days;10 cases obtained excellent
      results, 5 good, 3 fair, 2 poor at 3 months; 12 cases obtained excellent results,
      6 good, 1 fair, 1 poor at 6 months after operation. Postoperative clinical effect
      at 6 months was better than 3 d, and 3 months(P<0.05), and postoperative at 3
      months was better than 3 d(P<0.05). CONCLUSIONS: Percutaneous coblation
      nucleoplasty in treating cervical spondylotic radiculopathy can effectively
      relieve the pain of neck, shoulder and upper limb and can also relieve some
      associated symptoms such as headache and dizziness.

PMID- 30185008
TI  - [Analysis of clinical effects of anterior segmental decompression for multi
      segment cervical spondylotic myelopathy].
AB  - OBJECTIVE: To evaluate the clinical effects of anterior segmental decompression
      for the treatment of multi-segment cervical spondylotic myelopathy. METHODS: The
      clinical data of 84 patients with multi-segment cervical spondylotic myelopathy
      treated between August 2005 to March 2016 were retrospectively analyzed.
      According to different operative methods the patients were divided into control
      group and observation group, with 42 cases in each group. In the control group,
      including 26 males and 16 females, the age was (56.87+/-11.89) years old and
      course of disease was(7.91+/-3.71) years on average, the lesion segment occurred
      on C3-C6 of 36 cases and on C4-C7 of 6 cases. There were 24 males and 18 females
      in observation group, with the mean age of (54.58+/-12.56) years old, and the
      course of disease was(8.03+/-3.52) years, the lesion segment occurred on C3-C6 of
      34 cases, and on C4-C7 of 8 cases. The patients in control group were treated
      with posterior laminoplasty, and the patients in observation group underwent
      anterior segmental decompression. Operation time, intraoperative blood loss,
      hospitalization time, bone graft fusion time and complication rate were observed
      between two groups. JOA scores and Cobb angle of fusion segment were compared
      before operation and 3, 6, 9 months after operation. RESULTS: Operation time,
      intraoperative blood loss, hospitalization time and complication rate in
      observation group were significantly lower than in control group(P<0.05); the
      bone fusion time in observation group was significantly lower than in control
      group(P<0.01);3, 6, 9 months after surgery, JOA score and the segment Cobb angle
      in observation group were significantly higher than in control group(P<0.01).
      CONCLUSIONS: Anterior segmental decompression for the treatment of multi-segment
      cervical spondylotic myelopathy has obvious advantages of less vertebral
      resection, thorough decompression, good stability, less postoperative
      complications, which can effectively promote the recovery of the spinal cord
      function and vertebral stability.

PMID- 30185009
TI  - [Clinical study of the application of enhanced recovery after surgery in cervical
      spondylotic myelopathy].
AB  - OBJECTIVE: To evaluate the role of enhanced recovery after surgery in treating
      cervical spondylotic myelopathy. METHODS: The clinical data of 55 patients with
      cervical spondylotic myelopathy underwent surgical treatment from January 2012 to
      December 2015 were retrospectively analyzed. There were 30 males and 25 females,
      age from 36 to 71 years old with an average of (45.2+/-3.2) years, course of
      disease was for 1 to 12 months with an average of (4.5+/-1.8) months. The concept
      of enhanced recovery after surgery and perioperative management were applied to
      surgical treatment in 35 patients (study group), and the same period, 20 patients
      without strategy of enhanced recovery after surgery (control group). Thirty-eight
      patients were treated by anterior cervical discectomy decompression and
      fixation(ACDF), 17 patients were treated by posterior single-open door
      laminoplasty decompression. The activity time out of bed, hospitalization days
      after surgery were compared between two groups. Japanese Orthopaedic Association
      (JOA) score and visual analogue score(VAS) before operation, after operation at
      1, 7, 30 days and 6, 12 months was respectively used to evaluate the neurological
      function and pain. RESULTS: All the patients were followed up for 12 to 18 months
      with an average of (14.3+/-1.5) months. There was no significant difference in
      age, gender, surgical methods, preoperative VAS, JOA score between two groups
      (P>0.05). The activity time out of bed was 3 to 8 h with an average of (5.54+/
      1.54) h, postoperative hospitalization time was 3 to12 d with an average of
      (5.62+/-1.59) d in study group, while in control group, the activity time out of
      bed was 24 to 48 h with an average of (18.80+/-4.78) h, and postoperative
      hospitalization time was 7 to 17 d with an average of (9.85+/-1.94) d; there was
      significant difference between two groups (P<0.01). There was significant
      difference in VAS and JOA scores between two groups at 1, 7, 30 d after operation
      (P<0.01), and there was no significant difference at 6, 12 months after
      operation(P>0.05). There were no neurologic function deterioration, hematoma,
      wound infection, internal fixation loosening and other complications in study
      group during hospitalization and following-up;there were 2 cases of superficial
      wound infection in the control group, who healed by dressing change for 2
      weeks;there was no significant difference between two groups(P>0.05).
      CONCLUSIONS: The strategy of enhanced recovery after surgery in treating cervical
      spondylotic myelopathy can promote the early recovery, shorten the length of stay
      and improve the patient's degree of satisfaction.

PMID- 30185010
TI  - [Effect of the proximal level on post-laminoplasty loss of lordosis].
AB  - OBJECTIVE: To analyze the effect whether or not retaining muscle ligament complex
      of C2 attachment on cervical spine kyphotic deformity after single open-door
      laminoplasty. METHODS: A total 40 patients with cervical spondylotic myelopathy
      underwent single open-door laminoplasty from February 2011 to June 2014 were
      retrospectively analyzed. Of them, single open-door for C3-C6 was 40 cases (group
      A), including 28 males and 12 females, with an average age of (68.4+/-9.3) years
      old;and single open-door for C4-C6 plus C3 laminectomy decompression (in order to
      protect the muscle ligament complex of C2 attachment) was 40 cases (group B),
      including 26 males and 14 females, with an average age of (66.8+/-8.4) years old.
      Japanese Orthopaedic Association (JOA) score, visual analogue scale (VAS), Cobb
      angle of sagittal plane from C2-C7, cervical range of motion were used to
      evaluate effects before operation and at the latest follow-up. RESULTS: All the
      patients were followed up from 24 to 31 months with an average of(26.5+/-3.4)
      months. There was no significant differences in VAS, JOA scores and cervical
      range of motion before surgery between two groups (P>0.05) and all above items
      were significantly improved at the latest follow-up (P<0.05), but there was no
      significant difference between two groups(P>0.05). There was no significant
      difference in cervical Cobb angle before surgery between two groups(P>0.05), and
      postoperative Cobb angle had obviously improved in two groups(P<0.05), but the
      improvement of group B was better than that of group A. CONCLUSIONS: Starting the
      laminoplasy on C4 level and retainning the muscle ligament complex of C2
      attachment can obviouly decrease cervical spine syphotic deformity.

PMID- 30185011
TI  - [Effect of Bryan cervical disc replacement on cervical curvature and replacement
      segment in treating cervical spondylosis].
AB  - OBJECTIVE: To investigate the effect of Bryan cervical disc replacement on
      cervical curvature and replacement segment in the treatment of cervical
      spondylosis, and analyze its clinical efficacy. METHODS: Forty-nine patients
      underwent Bryan artificial cervical disc replacement from August 2010 to August
      2013 were retrospectively analyzed. There were 26 males and 23 females, aged from
      27 to 66 years old with an average of 48.5 years. Including 21 cases of nerve
      root type, 16 cases of spinal cord type, 12 cases of mixed type. And 21 cases
      were single segment replacement, 28 cases were double segments replacement.
      Preoperative and postoperative pain was compared using visual analogue
      scale(VAS);cervical function was observed by Japanese Orthopedic Association
      Scores (JOA) and Neck Disability Index (NDI);cervical lordosis curvature,
      function spinal unit(FSU) curvature, activities of replacement and adjacent
      segment, FSU activity were measured by cervical X-rays. Clinical effects were
      evaluated by the Odom method. RESULTS: All the patients were followed up for 18.5
      to 37.3 months with an average of 33.1 months. Pvoperative VAS, JOA, NDI scores
      were 7.08+/-1.55, 5.2+/-1.9, 39.96+/-7.06 before operation, 3.76+/-2.33, 13.20+/
      1.20, 25.20+/-6.64 at 3 months after operation, and 2.80+/-1.50, 14.3+/-1.6,
      24.24+/-7.89 at the last follow-up. Patients at three months and the last follow
      up after operation were obviously improved in their VAS, JOA, and NDI scores
      (P<0.05). There was no significant difference between the scores at last follow
      up and 3 months after operation. Cervical lordosis changed from (10.64+/-4.26)
      degrees  preoperatively to (13.68+/-4.56)  degrees  at the last follow-up;the FSU
      curvature from (5.40+/-0.41)  degrees to (9.92+/-2.00)  degrees at the last
      follow-up (P<0.05). The range of motion of the cervical spine preoperatively, 3
      month postoperatively, and at the last follow-up were(70.84+/-6.17) degrees ,
      (60.00+/-6.58) degrees , (71.48+/-4.61) degrees ; FSU activities were(12.00+/
      0.49) degrees , (9.36+/-0.26) degrees , (12.52+/-0.33) degrees ;the activities of
      replacement segment were (10.48+/-0.67) degrees , (7.24+/-0.34) degrees , (9.28+/
      0.36) degrees ;the activities of upper segment of replacement were (10.52+/-0.60)
      degrees , (8.60+/-0.30) degrees , (10.44+/-0.43) degrees ;the activities of lower
      segment of replacement were (8.48+/-0.40) degrees , (6.56+/-0.36) degrees ,
      (9.60+/-0.39) degrees ;there were significant differences in above items
      preoperatively and 3 months postoperatively(P<0.05); and there were no
      significant difference preoperatively and at the last follow-up(P>0.05).
      Pharyngeal discomfort and hoarseness occurred in 5 cases, and were recovered
      within 2 weeks after operation;heterotopic ossification occurred in 1 case at 6
      months after operation;displacement of prosthesis occurred in 1 case at 12 months
      after operation. Based on Odom standard to evaluate the clinical outcome, 20
      cases obtained excellent results, with 27 good, 2 general. CONCLUSIONS: Bryan
      artificial cervical disc replacement not only generate good clinical effects, but
      may also restore the cervical lordosis and FSU curvature, while retaining the
      activities of replacement segment, and restoring overall cervical biomechanical
      functions.

PMID- 30185012
TI  - [Efficacy evaluation of modified lamina osteotomy replantation versus traditional
      lamina osteotomy replantation in treating lumbar disc herniation with lumbar
      instability].
AB  - OBJECTIVE: To evaluate the clinical effects of modified lamina osteotomy
      replantation versus traditional lamina osteotomy replantation in the treatment of
      lumbar disc herniation with lumbar instability. METHODS: The clinical data of 146
      patients with unilateral lumbar disc herniation with lumbar instability underwent
      surgical treatment from March 2008 to March 2013 were retrospectively analyzed.
      Patients were divided into two groups according to osteotomy replantation
      pattern. There were 77 patients in the traditional group (underwent traditional
      lamina osteotomy replantation), including 42 males and 35 females with an average
      age of (49.4+/-18.5) years;the lesions occurred on L4,5 in 46 cases, on L55S1 in
      31 cases. There were 69 patients in modified group (underwent modified lamina
      osteotomy replantation), including 37 males and 32 females with an average age of
      (49.8+/-17.9) years;the lesions occurred on L4,5 in 40 cases, on L5S1 in 29
      cases. The operation time, intraoperative blood loss, complication rate during
      operation, lamina healing rate, recurrence rate of low back and leg pain were
      compared between two groups. Visual analogue scales (VAS) and Japanese Orthopadic
      Association (JOA) scores were used to evaluate the clinical effects. RESULTS: The
      operation time and intraoperative blood loss were similar between two group
      (P>0.05). There was significantly different in nerve injury rate(5.80% vs 16.9%)
      and dural injury rate(1.45% vs 9.09%) between modified group and traditional
      group(P<0.05). The recurrent rate of low back pain of modified group was higher
      (91.30%, 63/69) than that of traditional group (76.62%, 59/77), and the
      intervertebral fusion rate of modified group was lower(8.70%, 6/69) than that of
      traditional group (29.9%, 23/77) at 3 years after operation. Postoperative VAS
      scores of all patients were significantly decreased at 6 months, 1, 2, 3 years,
      and JOA scores were obviously increased (P<0.05). At 1, 2, 3 years after
      operation, VAS scores of modified group were significantly lower than that of
      traditional group(P<0.05), and JOA scores of modified group were higher than that
      of traditional group(P<0.05). CONCLUSIONS: Modified lamina osteotomy replantation
      has better long-term efficacy(in the aspect of recurrent rate of low back pain,
      intervertebral fusion rate, VAS and JOA score at three years follow-up) in
      treating lumbar disc herniation with instability.

PMID- 30185013
TI  - [Combining K-line to analyse the relationship between cervical range of motion of
      patients with ossification of cervical posterior longitudinal ligament and
      surgical prognosis].
AB  - OBJECTIVE: Combining K-line (the connecting line of the midpoint of C2 and C7
      spinal canal on the cervical lateral X-ray film) to analyze the relationship
      between cervical range of motion of patients with ossification of posterior
      longitudinal ligament (OPLL) and surgical prognosis. METHODS: A total 42 patients
      with ossification of cervical posterior longitudinal ligament underwent cervical
      posterior single open-door laminoplasty between April 2014 and March 2017 were
      retrospectively ananyzed. The patients were dividing into K-line (+) group and K
      line (-) group according to the position realationship of OPLL and K-line. The
      lesion of ossification of the posterior longitudinal ligament was not over than
      the K-line known as K-line (+). Conversely, the lesion of ossification of the
      posterior longitudinal ligament crossing the K-line was called K-line (-).
      Preoperative and postoperative 3 months JOA scores were observed, and
      postoperative 3 months JOA improvement rate were computed to assess patient's
      neurological function recovery. Preoperation and postoperative 3 months, OPLL
      occupation ratio (OOR), cervical lordotic angles (CLA) and cervical lordotic
      value (CLV) were measured respectively. The realationship between postoperative
      neurologic functional recovery in patients of CLV>0 group and CLV<=0 group was
      evaluated in different K-line subgroups. RESULTS: For the patients in K (+) group
      and K (-) group, preoperative CLA were (14.7+/-9.6) degrees  and (-6.4+/-9.5)
      degrees (P<0.05) respectively, postoperative at 3 months CLA were (14.0+/-8.0)
      degrees  and (-1.4+/-10.4) degrees (P<0.05) respectively; preoperative JOA scores
      were 10.9+/-3.2 and 11.2+/-2.5 (P>0.05) respectively, postoperative at 3 months
      JOA scores were 14.2+/-1.8 and 12.6+/-2.2 (P<0.05) respectively, and
      postoperative at 3 months JOA score improvement rate were (54.7+/-17.6)% and
      (25.5+/-15.7)%(P<0.05) respectively. In the K-line (+) group, there were 29
      patients in CLV>0 group at 3 months after operation, with improvement rate of
      (52.3+/-17.2)%, and 4 patients in CLV<=0 group, with improvement rate of (72.2+/
      7.8)%. The improvement rate of the patients in CLV<=0 group was significantly
      better than that of the patients in CLV>0 group (P<0.05). CONCLUSIONS: No matter
      whether the ossification of cervical posterior longitudinal ligament was
      classified as K-line (+) or K-line (-), the cervical posterior single open-door
      laminoplasty can improve the neurological symptoms of patients, especially the
      patients in the K-line(+) group with better prognosis. The patinets in K-line(+)
      group, when postoperative at 3 months CLV>0, their improvement rate was lower
      than that of the patients with postoperative at 3 months CLV<=0.

PMID- 30185014
TI  - [Experimental study on improvement of blood supply timeliness of rabbits with
      vertebral artery type of cervical spondylosis by massage].
AB  - OBJECTIVE: Establishing a rabbit model of vertebral artery type of cervical
      spondylosis(CSA) and to observe the characteristics of timeliness in improving
      the blood flow of vertebral artery by massage, and discusse the material basis of
      this timeliness based on NPY and ET-1. METHODS: Fifty New Zealand healthy and
      white rabbits, 6-month-old, the body mass of (2.0+/-0.5) kg, with half males and
      half females, were randomly divided into blank group, model group, three massage
      groups(including massage for 10 min, 20 min, and 30 min group by random number
      table), 10 rabbits in each group. In addition to the blank group, CSA rabbit
      model was made by injection of sclerosing agent in other groups. The rabbits of
      massage for 10 min, 20 min, and 30 min groups received the massage therapy of
      corresponding duration, one times a day, continuous 10 days. The blood flow of
      vertebral artery in each group was detected by PeriFlux5000 laser doppler, and
      the contents of NPY and ET-1 in serum were detected by ELISA before and after
      treatment. RESULTS: Changes in blood flow of vertebral artery before and after
      treatment:there was no significant difference between model group and massage for
      10 min group;there was significant difference between model group and massage for
      20, 30 min groups(P<0.01); there was significant difference between massage for
      10 min group and massage for 20, 30 min groups(P<0.01); there was no significant
      difference between massage for 20 min group and massage for 30 min group. Changes
      of NPY content before and after treatment: there was significant difference
      between model group and massage for 10 min group(P<0.05); there was significant
      difference between model group and massage for 20, 30 min groups(P<0.01); there
      was significant difference between massage for 10 min group and massage for 20,
      30 min groups(P<0.01); there was no significant difference between massage for 20
      min group and massage for 30 min group. Changes of ET-1 content before and after
      treatment:there was no significant difference between model group and massage for
      10 min group;there was significant difference between model group and massage for
      20, 30 min groups(P<0.01); there was significant difference between massage for
      10 min group and massage for 20 min, 30 groups (P<0.01); there was no significant
      difference between massage for 20 min group and massage for 30 min group.
      CONCLUSIONS: Massage needed 20 min for rabbits with CSA can only significantly
      improve the blood flow of vertebral artery. However, prolonging the time of
      massage has no obvious effect. The material basis of this timeliness
      characteristic of massage is closely related to the change of NPY and ET-1 levels
      in serum.

PMID- 30185015
TI  - [Treatment of Pilon fractures complicated with soft tissue injury by plate and
      lag screw fixation via posterolateral approach].
AB  - OBJECTIVE: To evaluate the clinical effects of plate and lag screw fixation for
      treatment of Pilon fractures complicated with soft tissue injury via
      posterolateral approach. METHODS: From May 2013 to June 2016, 25 patients with
      Pilon fractures complicated with soft tissue injury underwent open reduction and
      internal fixation via posterolateral approach. There were 15 males and 10
      females, aged from 25 to 61 years old with an average of(39.6+/-0.2) years. Plate
      and lag screw fixation were used in operation. Healing of soft tissue contusion
      and abrasions in the ankle wounds and injuries were observed after operation. The
      Burwell-Charnley standard was applied to assess the quality of fracture reduction
      and the AOFAS Ankle foot scoring system(total score 100 points) was used to
      evaluate the clinical effects. RESULTS: All the patients were followed up from 6
      to 24 months with an average of 12 months. All operative wounds and soft tissue
      injuries were healed. According to the Burwell-Charnley standard, 22 cases
      obtained excellent results with anatomic reduction, while 2 cases were
      dissatisfied, and 1 case poor. The AOFAS ankle foot scores were 90.2+/-7.5 on
      average, with 20 cases of excellent results, 3 good, 2 fair. CONCLUSIONS: Plate
      and lag screw fixation by posterolateral approach in treating Pilon fracture
      complicated with soft tissue injury shows advantage of avoiding injury to the
      anteromedial skin and soft tissue, provides forceful fixation without further
      injury.

PMID- 30185016
TI  - [Lumbar canal stenosis caused by gout:a case report].

PMID- 30185017
TI  - [Rapid prototyping navigation template assisted cervical screw implantation:a
      review].
AB  - The cervical screw fixation has been used widely in the clinic setting due to the
      high fusion rate, immediate fixation of the surgical segment and good correction
      of the deformity. However, owing to the variation of anatomical structures and
      the narrow pedicle screws, it's rather difficult to implant the screws through
      traditional methods. The perforation rate of the screw is high, which can cause
      serious complications such as neurovascular injury. In recent years, rapid
      prototyping navigation templates have been reported in the appilication to assist
      cervical screw placement for improving the accuracy of screw placement. In this
      paper, we reviewed and summarized published literatures about navigation template
      assisted cervical screw implantation in the past 20 years, systematically
      introduced the methods of producing and using of navigation templates, the
      development of design concept and the status of application in cervical spine
      surgery. To date, relevant clinical and cadaveric studies confirm that the use of
      rapid prototyping navigation template assisted cervical screw placement in
      cervical surgery can reduce screw perforation rate, intraoperative ionizing
      radiation injury and operation time, which is worth applying in the clinical
      practice. However, specific clinical effects of different design types of
      navigation templates are not well summarized. As a result, more clinical and
      cadaveric studies comparing the accuracy and safety of navigation templates of
      different design types are needed to help clinicians select the appropriate
      navigation template for surgery.

PMID- 30185018
TI  - Transfusion practice in neonates.
AB  - Neonates, especially extremely low birth weight infants, are among the groups of
      patients undergoing transfusion frequently. Since they are exposed to higher
      specific transfusion risks compared to the patients of other age groups, there
      are many special aspects that must be considered for transfusion therapy in
      neonates. The transfusion risks in neonates include adverse outcomes specific for
      preterm infants as well as increased metabolic, immunologic, and infectious
      complications. To reduce the risks of transfusion-transmitted cytomegalovirus
      infection and transfusion-associated graft-versus-host disease, leukoreduced and
      irradiated cellular blood products should be used for all neonates. This review
      summarizes the risks of neonatal transfusion therapy, specific methods to reduce
      risk, and current trends and practices of red blood cell and platelet
      transfusions in neonates, to facilitate decision-making for neonatal transfusion.

PMID- 30185019
TI  - Ultrasound-Responsive Nanoparticulate for Selective Amplification of
      Chemotherapeutic Potency for Ablation of Solid Tumors.
AB  - Precision medicine requests preferential transportation of the pharmaceutical
      substances to the pathological site and impartation of localized therapeutic
      activities to the targeted cells. To accomplish this goal, we attempted a facile
      nanoscaled ultrasound-responsive delivery system, characterized by doxorubicin
      assembled with an amphiphilic copolymer (multiple of hydrophobic stearic segments
      tethered onto the hydrophilic pullulan backbone through ultrasound-labile oxyl
      alkylhydroxylamine linkage). As a consequence of the strategically installed
      ultrasound-labile oxyl-alkylhydroxylamine linkage to elicit the tailored
      segregation of the hydrophilic pullulan and the hydrophobic stearic segments upon
      ultrasound impetus, the constructed nanoscaled self-assembly presented
      distinctive structural destabilization behaviors and afforded spatiotemporal
      controlled liberation of the cytotoxic drugs. It is worthy to note that the
      ultrasound was determined to markedly lower the IC50 of the proposed system from
      over 10 MUg/mL to 2.33 MUg/mL (approximate 4-fold), thereby serving as a facile
      impetus to amplify the cytotoxic potency of the proposed drug delivery vehicles.
      Furthermore, drastic tumor ablation was validated by dosage of the proposed
      doxorubicin delivery system to T41 tumor-bearing mice accompanied by the tumor
      localized ultrasound impetus, while no observable adverse side effect was
      confirmed. Therefore, the results advocated our ultrasound-responsive delivery
      vehicle as a tempting strategy for precise spatiotemporal control of the release
      of the drug cargo, thus affording selectively amplified cytotoxic potency to the
      ultrasound-imposed site, which should be highlighted as important progress toward
      precision medicine.

PMID- 30185020
TI  - Thermodynamic Stability of DNA Duplexes Comprising the Simplest T -> dU
      Substitutions.
AB  - Members of the uracil-DNA glycosylase (UDG) enzyme family recognize and bind
      uracil, sequestering it within the binding site pocket and catalyzing the
      cleavage of the base from the deoxyribose, leaving an abasic site. The
      recognition and binding are passive and rely on innate dynamic motions of DNA
      wherein base pairs undergo thermally induced breakage and conformational
      fluctuations. Once the uracil breaks from its base pair, it can be recognized and
      bound by the enzyme, which then alters its conformation for sequestration and
      catalysis. Our results suggest that the thymine to uracil substitution, which
      differs only by a single methyl group, causes a destabilization of the duplex
      thermodynamics, which would lead to an increase in the population of the
      extrahelical state and increase the probability of uracil being recognized and
      excised from DNA by UDG. This destabilization is dependent on the identity of the
      nearest-neighbor base-pair stacks; a G.C nearest neighbor leads to thermal and
      enthalpic destabilization that is weaker that that seen with two A.T neighbors.
      In addition, uracil substitution yields a nearest-neighbor increase in the
      counterion uptake of the duplexes but decreases the level of immobilization of
      structural water for all substituted duplexes regardless of the neighbor identity
      or number of substitutions.

PMID- 30185021
TI  - Nanoscale Laponite as a Potential Shale Inhibitor in Water-Based Drilling Fluid
      for Stabilization of Wellbore Stability and Mechanism Study.
AB  - Shale hydration is the main reason causing wellbore instability in oil and gas
      drilling operations. In this study, nanoscale laponite as a shale inhibitor was
      employed to stabilize wellbores. The inhibition property of laponite suspensions
      was evaluated by an immersion experiment, linear swelling measurement, and a
      shale recovery test. Then the shale inhibition mechanism was studied by using
      capillary suction time (CST) measurement, a thixotropy study, plugging
      performance evaluation, and related theoretical analysis. Evaluation experiment
      results showed that laponite had a better inhibition property than widely used
      inhibitors of potassium chloride (KCl) and poly(ester amine) (PA). The mechanism
      study revealed that integration of several factors strengthened the inhibition
      property of laponite suspensions. Laponite nanoparticles could plug interlayer
      spaces of clays by electrostatic interaction to reduce water invasion; the "house
      of cards" structure of laponite suspensions enables large CST values and low free
      water contents; the excellent thixotropy of a laponite nanofluid could allow a
      nanofilm to form in order to reduce water invasion into the formation; the
      nanoscale laponite particles could substantially reduce the shale permeability
      and form less porous surfaces. Furthermore, laponite could considerably decrease
      the filtrate volume of the drilling fluid, while KCl and PA had negative
      influences on the properties of the drilling fluid. This approach described
      herein might provide an avenue to inhibit shale hydration.

PMID- 30185022
TI  - Source-Specific Health Risk Analysis on Particulate Trace Elements: Coal
      Combustion and Traffic Emission As Major Contributors in Wintertime Beijing.
AB  - Source apportionment studies of particulate matter (PM) link chemical composition
      to emission sources, while health risk analyses link health outcomes and chemical
      composition. There are limited studies to link emission sources and health risks
      from ambient measurements. We show such an attempt for particulate trace
      elements. Elements in PM2.5 were measured in wintertime Beijing, and the total
      concentrations of 14 trace elements were 1.3-7.3 times higher during severe
      pollution days than during low pollution days. Fe, Zn, and Pb were the most
      abundant elements independent of the PM pollution levels. Chemical fractionation
      shows that Pb, Mn, Cd, As, Sr, Co, V, Cu, and Ni were present mainly in the
      bioavailable fraction. Positive matrix factorization was used to resolve the
      sources of particulate trace elements into dust, oil combustion, coal combustion,
      and traffic-related emissions. Traffic-related emission contributed 65% of total
      mass of the measured elements during low pollution days. However, coal combustion
      dominated (58%) during severe pollution days. By combining element-specific
      health risk analyses and source apportionment results, we conclude that traffic
      related emission dominates the health risks by particulate trace elements during
      low pollution days, while coal combustion becomes equally or even more important
      during moderate and severe pollution days.

PMID- 30185023
TI  - Optical Control of Nanoparticle Catalysis Influenced by Photoswitch Positioning
      in Hybrid Peptide Capping Ligands.
AB  - Here, we present an in-depth analysis of structural factors that modulate peptide
      capped nanoparticle catalytic activity via optically driven structural
      reconfiguration of the biointerface present at the particle surface. Six
      different sets of peptide-capped Au nanoparticles were prepared, in which an
      azobenzene photoswitch was incorporated into one of two well-studied peptide
      sequences with known affinity for Au, each at one of three different positions:
      the N- or C-terminus or mid-sequence. Changes in the photoswitch isomerization
      state induce a reversible structural change in the surface-bound peptide, which
      modulates the catalytic activity of the material. This control of reactivity is
      attributed to changes in the amount of accessible metallic surface area available
      to drive the reaction. This research specifically focuses on the effect of the
      peptide sequence and photoswitch position in the biomolecule, from which
      potential target systems for on/off reactivity have been identified.
      Additionally, trends associated with photoswitch position for a peptide sequence
      (Pd4) have been identified. Integrating the azobenzene at the N-terminus or
      central region results in nanocatalysts with greater reactivity in the trans and
      cis conformations, respectively, however, positioning the photoswitch at the C
      terminus gives rise to a unique system that is reactive in the trans conformation
      and partially deactivated in the cis conformation. These results provide a
      fundamental basis for new directions in nanoparticle catalyst development to
      control activity in real time, which could have significant implications in the
      design of catalysts for multistep reactions using a single catalyst.
      Additionally, such a fine level of interfacial structural control could prove to
      be important for applications beyond catalysis, including biosensing, photonics,
      and energy technologies that are highly dependent on particle surface structures.

PMID- 30185024
TI  - A Room-Temperature Hybrid Lead Iodide Perovskite Ferroelectric.
AB  - Organic-inorganic hybrid perovskite, [CH3NH3]PbI3, holds a great potential for
      next-generation solar devices. However, whether the ferroelectricity exists in
      [CH3NH3]PbI3 and results in the ultrahigh performance is not at present clear.
      Beyond that, no hybrid lead iodide perovskite ferroelectric has yet been found.
      Here, using precise molecular modifications, we successfully designed a room
      temperature hybrid perovskite ferroelectric, [(CH3)3NCH2I]PbI3. Because of the
      high-symmetry and nearly spherical shape of [(CH3)4N]+ cation, [(CH3)4N]PbI3
      crystallizes in a centrosymmetric space group P63/ m at room temperature and
      undergoes a structural phase transition at 184 K. Accompanied by the introduction
      of halogen atoms on the cation from F to I, the phase transition temperature
      gradually increases to 312 K and the space group transforms into a polar C2 at
      room temperature. The strongest halogen bond energy of [(CH3)3NCH2I]-I and the
      largest volume of [(CH3)3NCH2I]+ among these compounds might be possible reasons
      for the stabilization of ordered [(CH3)3NCH2I]+ cation array and further
      reservation of its ferroelectricity at relatively high temperature. This work
      provides an efficient molecular design strategy toward the targeted harvest of
      room-temperature organic-inorganic perovskite ferroelectrics, and should inspire
      further exploration of the interplay between structure and ferroelectricity. The
      discovery of lead iodide perovskite ferroelectric also offers a foothold to the
      possibility for the existence of ferroelectricity in [CH3NH3]PbI3.

PMID- 30185025
TI  - Carbonic Anhydrase IX-Targeted Near-Infrared Dye for Fluorescence Imaging of
      Hypoxic Tumors.
AB  - Use of tumor-targeted fluorescence dyes to help surgeons identify otherwise
      undetected tumor nodules, decrease the incidence of cancer-positive margins, and
      facilitate localization of malignant lymph nodes has demonstrated considerable
      promise for improving cancer debulking surgery. Unfortunately, the repertoire of
      available tumor-targeted fluorescent dyes does not permit identification of all
      cancer types, raising the need to develop additional tumor-specific fluorescent
      dyes to ensure localization of all malignant lesions during cancer surgeries. By
      comparing the mRNA levels of the hypoxia-induced plasma membrane protein carbonic
      anhydrase IX (CA IX) in 13 major human cancers with the same mRNA levels in
      corresponding normal tissues, we document that CA IX constitutes a nearly
      universal marker for the design of tumor-targeted fluorescent dyes. Motivated by
      this expression profile, we synthesize two new CA IX-targeted near-infrared (NIR)
      fluorescent imaging agents and characterize their physical and biological
      properties both in vitro and in vivo. We report that conjugation of either
      acetazolamide or 6-aminosaccharin (i.e., two CA-IX-specific ligands) to the NIR
      fluorescent dye, S0456, via an extended phenolic spacer creates a brightly
      fluorescent dye that binds CA IX with high affinity and allows rapid
      visualization of hypoxic regions of solid tumors at depths >1 cm beneath a tissue
      surface. Taken together, these data suggest that a CA IX-targeted NIR dye can
      constitute a useful addition to a cocktail of tumor-targeted NIR dyes designed to
      image all human cancers.

PMID- 30185026
TI  - Poly( N-isopropylacrylamide)-Grafted Polydimethylsiloxane Substrate for
      Controlling Cell Adhesion and Detachment by Dual Stimulation of Temperature and
      Mechanical Stress.
AB  - Stretchable temperature-responsive cell culture surfaces composed of poly( N
      isopropylacrylamide) (PIPAAm) gel-grafted polydimethylsiloxane (PIPAAm-PDMS) were
      prepared to demonstrate that dual stimulation of temperature and mechanical
      stress extensively altered graft polymer thickness, surface wettability, and cell
      detachment behavior. The PIPAAm-PDMS surface was hydrophilic and hydrophobic
      below and above the lower critical solution temperature, respectively, which was
      ascribed to the phase transition of PIPAAm chains. When uniaxial stretching was
      applied, the grafted PIPAAm gel surface was modulated to be more hydrophobic as
      shown by an increase in the contact angle. Atomic force microscopy observation
      revealed that uniaxial stretching made the grafted gel layer thinner and deformed
      the nanoscale aggregates of the grafted PIPAAm gel, implying extension of the
      PIPAAm chains. The stretched PIPAAm-PDMS became more cell adhesive than the
      unstretched PIPAAm-PDMS at 37  degrees C. Furthermore, dual stimulation,
      shrinking the already stretched PIPAAm-PDMS and decreasing the temperature,
      induced more rapid cell detachment than only a change in temperature did.
      Similarly, upon comparison with a single stimulation of a change in temperature
      or mechanical stress, dual stimulation accelerated cell sheet detachment and
      harvesting. This new stretchable and temperature-responsive culture surface can
      easily adjust the surface property to a different cell adhesiveness by
      appropriately combining each stimulus and enable the fabrication of cell sheets
      of various species.

PMID- 30185027
TI  - A Novel Method for the Metallization of 3D Silicon Induced by Metastable Copper
      Nanoparticles.
AB  - The development of efficient copper deposition processes in high-aspect-ratio
      silicon structures is still a key technological issue for the microelectronic
      industry. We describe here a new process for the deposition of copper thin films
      in three-dimensional (3D) structures induced by the decomposition of a copper
      amidinate precursor in solution under a moderate H2 pressure. The reduction of a
      metal precursor under soft conditions (3 bar, 110  degrees C) affords the
      preparation of a high-purity, conformal metallic layer. We unveil a novel
      deposition mechanism driven by colloidal copper nanoparticles (NPs) in solution
      that behave as a reservoir of metastable metallic NPs that eventually condense as
      a solid film on all immersed surfaces. The film growth process is characterized
      by time-resolved analyses of the NPs in the colloidal state (nuclear magnetic
      resonance NMR and UV-vis spectra) and of the NPs and metallic layer on substrates
      (transmission electron microscopy TEM, and scanning electron microscopy SEM).
      Major deposition stages of this process are proposed and the conformal
      metallization of 3D silicon substrates is successfully achieved. This method is
      transposable to other metallic layers such as silver or nickel.

PMID- 30185028
TI  - Understanding Ni(II)-Mediated C(sp3)-H Activation: Tertiary Ureas as Model
      Substrates.
AB  - We report a mechanistic study of C(sp3)-H bond activation mediated by nickel.
      Cyclometalated Ni(II) ureate [(PEt3)Ni(kappa3- C,N,N-(CH2)N(Cy)(CO)N((N)-quinolin
      8-yl))] was synthesized and isolated from the urea precursor,
      (Me)(Cy)N(CO)N(H)(quinolin-8-yl), via C(sp3)-H activation. We investigated the
      effects of solvents and base additives on the rate of C-H activation. Kinetic
      isotope effect experiments showed that C-H activation is rate determining.
      Through deuterium labeling and protonation studies, we also showed that C-H
      activation can be reversible. We extended this reaction to a range of ureas with
      primary and secondary C(sp3)-H bonds, which activate readily to form analogous
      nickelated products. Finally, we showed that carboxylate additives assist with
      both ligand dissociation and initial N-H bond activation, consistent with a
      concerted metalation-deprotonation mechanism.

PMID- 30185029
TI  - Temperature-Dependent Complex Coacervation of Engineered Elastin-like Polypeptide
      and Hyaluronic Acid Polyelectrolytes.
AB  - Coacervates have enormous potential due to their diverse functional properties
      supporting a wide number of applications in personal care products,
      pharmaceuticals, and food processing. Normally, separation of coacervate phases
      is induced by changes in pH, ionic strength, and/or polyelectrolyte
      concentration. This study investigates the microphase separation and coacervate
      complex formation of two natural polyelectrolytes, elastin-like polypeptides
      (ELPs) and hyaluronic acid (HA), as simple models for biological coacervates.
      These complex coacervates are formed over a wide range of stoichiometric molar
      charge ratios without the presence of salt or changes in pH and are primarily
      induced by changes in temperature. Unlike pure ELP solutions, the ELP/HA
      coacervates result in well-formed spherical particles after the temperature
      induced phase transition. We also note that the formation of these complex
      coacervates is reversible with low hysteresis. We have demonstrated via
      fluorescent imaging and dynamic light scattering that high positive/negative
      charge ratios at elevated temperatures produced 400-600 nm particles with
      relatively low polydispersity indices (PDIs) of ~0.1. Furthermore, dynamic light
      scattering, fluorescence microscopy, and optical microscopy revealed that the
      ratio of the two polyions strongly influenced the size and structure of these
      ELP/HA complex coacervates. Finally, we showed that the ELP/HA coacervates were
      able to sequester the hydrophobic fluorescent molecule pyrene, highlighting their
      potential for use as delivery vehicles for hydrophobic payloads.

PMID- 30185031
TI  - High Singlet Oxygen Yield Photosensitizer Based Polypeptide Nanoparticles for Low
      Power Near-Infrared Light Imaging-Guided Photodynamic Therapy.
AB  - NIR photosensitizer is attractive for photodynamic therapy (PDT). Low-power light
      irradiation and imaging-guided PDT makes it possible to increase tissue
      penetration depth. The pyrrole-substituted iodinated BODIPY (BDPI) molecule was
      designed and synthesized, and it possesses an intense NIR absorption and emission
      band, and exhibits a high singlet oxygen quantum yield (PhiDelta = 0.80) which
      leads remarkable cytotoxicity upon low power illumination (IC50 = 0.60 MUg/mL,
      6.1 mW/cm2). After being encapsulated with biocompatibility polypeptide PEG-PLys,
      polymeric micelles nanoparticles (PBDPI NPs) was obtained that are water
      dispersed and passively tumor-targetable. Such enhanced accumulation in tumor
      area makes it easily traced in vivo due to its NIR fluorescence. In addition,
      such nanoparticles offer an unprecedented photodynamic therapeutic effect by
      using a low-power irradiation light, which makes it possible to kill cancer cells
      in deep tissue efficiently.

PMID- 30185030
TI  - Cation-pi Interactions in the Benzylic Arylation of Toluenes with Bimetallic
      Catalysts.
AB  - A method to directly arylate toluene derivatives with aryl bromides to generate
      diarylmethanes, which are important building blocks in drug discovery, is
      described. In this method, KN(SiMe3)2 in combination with a (NIXANTPHOS)Pd
      catalyst accomplished the deprotonative activation of toluene derivatives to
      permit cross-coupling with aryl bromides. Good to excellent yields are obtained
      with a range of electron-rich to neutral aryl bromides. Both electron-rich and
      electron-poor toluene derivatives are well tolerated, and even 2-chlorotoluene
      performs well, providing a platform for introduction of additional
      functionalization. This discovery hinges on the use of a main group metal to
      activate toluene for deprotonation by means of a cation-pi interaction, which is
      secured by a bimetallic K(NIXANTPHOS)Pd assembly. Mechanistic and computational
      studies support acidification of toluene derivatives by the K+-cation- pi
      interaction, which may prove pertinent in the development of other, new reaction
      systems.

PMID- 30185032
TI  - Proteomic Analysis Reveals That an Extract of the Plant Lippia origanoides
      Suppresses Mitochondrial Metabolism in Triple-Negative Breast Cancer Cells.
AB  - Triple-negative breast cancer is an aggressive subtype of breast cancer with low
      5-year survival rates, high 3-year recurrence rates, and no known therapeutic
      targets. Recent studies have indicated that triple-negative breast cancers
      possess an altered metabolic state with higher rates of glycolysis, mitochondrial
      oxidative phosphorylation, and increased generation and utilization of
      tricarboxylic acid cycle intermediates. Here, we utilized label-free quantitative
      proteomics to gain insight into the anticancer mechanisms of a methanolic extract
      from the Central American plant Lippia origanoides on MDA-MB-231 triple-negative
      breast cancer cells. The L. origanoides extract dysregulated mitochondrial
      oxidative phosphorylation by suppressing the expression of several subunits of
      Complex I of the electron transport chain, and inhibited cellular metabolism by
      down-regulating key tricarboxylic acid cycle enzymes and mitochondrial lipid and
      amino-acid metabolic pathways. Our study also revealed that treatment with the
      extract activated the stress response and pathways related to cell-cycle
      progression and DNA repair. Overall, our results reveal compelling new evidence
      that the extract from L. origanodes triggers rapid irreversible apoptosis in MDA
      MB-231 cells by effectively 'starving' the cells of metabolites and ATP. We
      continue to study the specific bioactive components of the extract in the search
      for novel, highly effective mitochondrial inhibitors to selectively target triple
      negative breast cancer.

PMID- 30185033
TI  - Aliphatic C-H Oxidations for Late-Stage Functionalization.
AB  - The atomistic change of C( sp3)-H to C( sp3)-O can have a profound impact on the
      physical and biological properties of small molecules. Traditionally, chemical
      synthesis has relied on pre-existing functionality to install new functionality,
      and directed approaches to C-H oxidation are an extension of this logic. The
      impact of developing undirected C-H oxidation reactions with controlled site
      selectivity is that scientists gain the ability to diversify complex structures
      at sites remote from existing functionality, without having to carry out
      individual de novo syntheses. This Perspective offers a historical view of why,
      as recently as 2007, it was thought that the differences between aliphatic C-H
      bonds of the same bond type (for example, 2 degrees  aliphatic) were not large
      enough to distinguish them preparatively with small-molecule catalysis in the
      absence of directing groups or molecular recognition elements. We give an account
      of the discovery of Fe(PDP)-catalyzed non-directed aliphatic C-H hydroxylations
      and how the electronic, steric, and stereoelectronic rules for predicting site
      selectivity that emerged have affected a shift in how the chemical community
      views the reactivity among these bonds. The discovery that site-selectivity could
      be altered by tuning the catalyst [i.e., Fe(CF3-PDP)] with no changes to the
      substrate or reaction now gives scientists the ability to exert control on the
      site of oxidation on a range of functionally and topologically diverse compounds.
      Collectively, these findings have made possible the emerging area of late-stage C
      H functionalizations for streamlining synthesis and derivatizing complex
      molecules.

PMID- 30185034
TI  - Nanobeam X-ray Fluorescence Dopant Mapping Reveals Dynamics of in Situ Zn-Doping
      in Nanowires.
AB  - The properties of semiconductors can be controlled using doping, making it
      essential for electronic and optoelectronic devices. However, with shrinking
      device sizes it becomes increasingly difficult to quantify doping with sufficient
      sensitivity and spatial resolution. Here, we demonstrate how X-ray fluorescence
      mapping with a nanofocused beam, nano-XRF, can quantify Zn doping within in situ
      doped III-V nanowires, by using large area detectors and high-efficiency focusing
      optics. The spatial resolution is defined by the focus size to 50 nm. The
      detection limit of 7 ppm (2.8 * 1017 cm-3), corresponding to about 150 Zn atoms
      in the probed volume, is bound by a background signal. In solar cell InP
      nanowires with a p-i-n doping profile, we use nano-XRF to observe an
      unintentional Zn doping of 5 * 1017 cm-3 in the middle segment. We investigated
      the dynamics of in situ Zn doping in a dedicated multisegment nanowire, revealing
      significantly sharper gradients after turning the Zn source off than after
      turning the source on. Nano-XRF could be used for quantitative mapping of a wide
      range of dopants in many types of nanostructures.

PMID- 30185035
TI  - Mixed Explicit-Implicit Solvation Approach for Modeling of Alkane Complexation in
      Water-Soluble Self-Assembled Capsules.
AB  - The host-guest binding properties of a water-soluble resorcinarene-based cavitand
      are examined using density functional theory methodology. Experimentally, the
      cavitand has been observed to self-assemble in aqueous solution into both 1:1 and
      2:1 host/guest complexes with hydrophobic guests such as n-alkanes. For n-decane,
      equilibrium was observed between the 1:1 and 2:1 complexes, while 1:1 complexes
      are formed with shorter n-alkanes and 2:1 complexes are formed with longer ones.
      These findings are used to assess the standard quantum chemical methodology. It
      is first shown that a rather advanced computational protocol (B3LYP-D3(BJ)/6
      311+G(2d,2p) with COSMO-RS and quasi-rigid-rotor-harmonic-oscillator) gives very
      large errors. Systematic examination of the various elements of the methodology
      shows that the error stems from the implicit solvation model. A mixed explicit
      implicit solvation protocol is developed that involves a parametrization of the
      hydration free energy of water such that water cluster formation in water is
      predicted to be thermoneutral. This new approach is demonstrated to lead to a
      major improvement in the calculated binding free energies of n-alkanes,
      reproducing very well the 1:1 versus 2:1 host/guest binding trends.

PMID- 30185036
TI  - Analysis of the Distinct Pattern Formation of Globular Proteins in the Presence
      of Micro- and Nanoparticles.
AB  - Pattern formation during evaporation of biofluids has numerous biomedical
      applications, e.g., in disease identification. The drying of a bidisperse
      colloidal droplet involves formation of coffee ring patterns owing to the
      deposition of constituent particles. In the present study, we examine the
      distinctly different pattern formations during the drying of a colloidal solution
      depending on the nature of the constituent proteins. The pattern formations of
      two oppositely charged proteins, namely HSA and lysozyme, have been studied in
      the presence of fluorescence polystyrene beads of two different sizes (providing
      better image contrast for further analysis). The variation of pattern formation
      has been studied by varying the concentrations of the proteins as well as the
      particles. Furthermore, using image analysis, the patterns are segmented into
      different regions for quantification. To explain the variations in the patterns,
      we delve into the interplay of the interactions, especially the capillary and the
      DLVO forces (between the particles and the substrate). The developed methodology
      based on the coffee ring effect may be used to identify individual proteins.

PMID- 30185037
TI  - Anti-Multiple Myeloma Activity of Nanobody-Based Anti-CD38 Chimeric Antigen
      Receptor T Cells.
AB  - Chimeric antigen receptor T cells (CAR-Ts) are a promising strategy for the
      treatment of many cancers, including multiple myeloma (MM), a hematological
      malignancy characterized by the high expression of CD38. To broaden the
      applications of using CD38 as a therapeutic target for the disease, we developed
      a new nanobody against CD38 and constructed a CD38-CAR that was composed of this
      nanobody as the targeting domain, and 4-1BB and CD3zeta as the costimulatory and
      activating domains, in a lentiviral vector. CD3+ T cells from healthy individuals
      were transduced with the CD38-CAR at an efficiency higher than 60%, as determined
      by CD38-CAR expression using flow cytometry. The CD38-CAR-Ts proliferated
      efficiently and produced more inflammatory cytokines, such as IL-2, IFN-gamma,
      and TNF-alpha, when activated. The CD38-CAR-Ts effectively lysed CD38+ MM cell
      lines, including LP-1, RPMI 8226, OPM2, and MOLP8, and primary MM cells from
      multiple myeloma patients. The specificity was demonstrated by the fact that CD38
      CAR-Ts showed little cytotoxicity on LP-1 cells with CD38 knocked out or on K562
      cells, which do not express CD38. CD38-CAR-Ts appeared to have a very slight
      cytotoxicity against CD38+ fractions of T cells, B cells, and natural killer
      cells. In addition, the lysis of CD34+ hematopoietic progenitor cells did not
      completely inhibit the development of colony-forming units. In vivo, CD38-CAR-Ts
      inhibited tumor growth in NOD/SCID mice that were subcutaneously inoculated with
      RPMI 8226 cells. These results demonstrate that the CD38-CAR-Ts constructed with
      the anti-CD38 nanobody are a promising approach for the treatment of multiple
      myeloma.

PMID- 30185038
TI  - Equilibrium and Kinetic Unfolding of GB1: Stabilization of the Native State by
      Pressure.
AB  - NMR spectroscopy allows an all-atom view on pressure-induced protein folding,
      separate detection of different folding states, determination of their
      population, and the measurement of the folding kinetics at equilibrium. Here, we
      studied the folding of protein GB1 at pH 2 in a temperature and pressure
      dependent way. We find that the midpoints of temperature-induced unfolding
      increase with higher pressure. NMR relaxation dispersion experiments disclosed
      that the unfolding kinetics slow down at elevated pressure while the folding
      kinetics stay virtually the same. Therefore, pressure is stabilizing the native
      state of GB1. These findings extend the knowledge of the influence of pressure on
      protein folding kinetics, where so far typically a destabilization by increased
      activation volumes of folding was observed. Our findings thus point toward an
      exceptional section in the pressure-temperature phase diagram of protein
      unfolding. The stabilization of the native state could potentially be caused by a
      shift of p Ka values of glutamates and aspartates in favor of the negatively
      charged state as judged from pH sensitive chemical shifts.

PMID- 30185039
TI  - Immunomodulating Nanomedicine for Cancer Therapy.
AB  - Nanomaterials offer unique advantages as drug-delivery vehicles for cancer
      therapeutics. For immuno-oncology applications, cancer nanomedicine should be
      developed beyond drug-delivery platforms. A greater emphasis on actively
      modulating host anticancer immunity using nanomaterials provides new avenues for
      developing novel cancer therapeutics.

PMID- 30185041
TI  - Using Theory To Reinterpret the Kinetics of Monofunctional Platinum Anticancer
      Drugs: Stacking Matters.
AB  - The monofunctional platinum drug phenanthriplatin (phenPt) blocks the replication
      of cancer cells even if it reacts with only one guanine base. However, there is
      still insufficient experimental data to improve its cytotoxicity and all
      previously proposed chemical modifications of the parent structure have resulted
      in a loss of activity. We use theoretical tools to illustrate the key steps in
      the biological mechanisms of phenPt; that is, its activation in water and the
      subsequent attack on DNA. Our simulations suggest that the measured kinetic
      parameters, which are based on free nucleobases in solution, need to be
      reinterpreted because the self-assembled stacked reactive adduct formed in the
      reaction is inaccessible in real DNA. The constants reported here will help guide
      future work in the synthesis of anticancer platinum drugs.

PMID- 30185040
TI  - Toward a Green Synthesis of Polyurethane/(Meth)acrylic Dispersions through
      Control of Colloidal Characteristics.
AB  - Polyurethane (PU)/acrylic waterborne hybrids are an attractive class of materials
      with wide application possibilities, but their synthesis typically requires
      significant quantities of solvent which has negative economic and environmental
      consequences. In this work, solvent-free and surfactant-free polyurethane
      (PU)/acrylic waterborne hybrids were obtained by synthesizing the PU prepolymer
      containing carboxylic groups directly in (meth)acrylic monomers that act as
      solvent. Then, the mixture is dispersed in water; the PU is chain-extended with
      diamines, and the (meth)acrylic monomers are polymerized. It was found that,
      against expectations, colloidal stability did not improve with the concentration
      of carboxylic groups that acted as stabilizing moieties. A combination of MALDI
      TOF MS analysis and Monte Carlo simulations revealed that the highly
      heterogeneous compositions of the short chains of the PU prepolymer and their
      reaction with the chain-extender in the aqueous phase were responsible for lack
      of control of the colloidal properties. This problem was overcome by using more
      hydrophobic chain-extenders that decrease the fraction of PU chains in the water
      phase. In this way high-solid-content stable dispersions with controlled particle
      size were obtained. Finally, the properties of the PU/(meth)acrylic films were
      studied in terms of mechanical properties and water resistance.

PMID- 30185042
TI  - DNA-Hybridization Detection on Si(100) Surfaces Using Light-Activated
      Electrochemistry: A Comparative Study between Bovine Serum Albumin and
      Hexaethylene Glycol as Antifouling Layers.
AB  - Light can be used to spatially resolve electrochemical measurements on a
      semiconductor electrode. This phenomenon has been explored to detect DNA
      hybridization with light-addressable potentiometric sensors and, more recently,
      with light-addressable amperometric sensors based on organic-monolayer-protected
      Si(100). Here, a contribution to the field is presented by comparing sensing
      performances when bovine serum albumin (BSA) and hexaethylene glycol (OEG6) are
      employed as antifouling layers that resist nonspecific adsorption to the DNA
      modified interface on Si(100) devices. What is observed is that both sensors
      based on BSA or OEG6 initially allow electrochemical distinction among
      complementary, noncomplementary, and mismatched DNA targets. However, only
      surfaces based on OEG6 can sustain electroactivity over time. Our results suggest
      that this relates to accelerated SiO x formation occasioned by BSA proteins
      adsorbing on monolayer-protected Si(100) surfaces. Therefore, DNA biosensors were
      analytically explored on low-doped Si(100) electrodes modified on the molecular
      level with OEG6 as an antifouling layer. First, light-activated electrochemical
      responses were recorded over a range of complementary DNA target concentrations.
      A linear semilog relation was obtained from 1.0 * 10-11 to 1.0 * 10-6 mol L-1
      with a correlation coefficient of 0.942. Then, measurements with three
      independent surfaces indicated a relative standard deviation of 4.5%. Finally,
      selectivity tests were successfully performed in complex samples consisting of a
      cocktail mixture of four different DNA sequences. Together, these results
      indicate that reliable and stable light-activated amperometric DNA sensors can be
      achieved on Si(100) by employing OEG6 as an antifouling layer.

PMID- 30185043
TI  - Gas Flow at the Ultra-nanoscale: Universal Predictive Model and Validation in
      Nanochannels of Angstrom-Level Resolution.
AB  - Gas transport across nanoscale pores is determinant in molecular exchange in
      living organisms as well as in a broad spectrum of technologies. Here, we report
      an unprecedented theoretical and experimental analysis of gas transport in a
      consistent set of confining nanochannels ranging in size from the ultra-nanoscale
      to the sub-microscale. A generally applicable theoretical approach quantitatively
      predicting confined gas flow in the Knudsen and transition regime was developed.
      Unlike current theories, specifically designed for very simple channel
      geometries, our approach can be applied to virtually all geometries, for which
      the probability distribution of path lengths for particle-interface collisions
      can be computed, either analytically or by numerical simulations. To generate a
      much needed benchmark experimental model, we manufactured extremely reproducible
      membranes with two-dimensional nanochannels. Channel sizes ranged from 2.5 to 250
      nm, and angstrom level of size control and interface tolerances were achieved
      using leading-edge nanofabrication techniques. We then measured gas flow in the
      Knudsen number range from 0.2 to 20. Excellent agreement between theoretical
      predictions and experimental data was found, demonstrating the validity and
      potential of our approach.

PMID- 30185044
TI  - Virtual Issue on Physical Chemistry in South Korea.

PMID- 30185045
TI  - Virtual Issue on Physical Chemistry in South Korea.

PMID- 30185046
TI  - Spotlights: Volume 9, Issue 17.

PMID- 30185047
TI  - Virtual Issue on Physical Chemistry in South Korea.

PMID- 30185048
TI  - Non-Drude Magneto-Transport Behavior in a Topological Crystalline Insulator/Band
      Insulator Heterostructure.
AB  - The Drude model is one of the most fundamental models used to understand the
      electronic carrier transport in materials, including recently discovered
      topological materials. Here, we present a magneto-transport study revealing the
      non-Drude transport behavior in a heterostructure of topological crystalline
      insulator (TCI) SnTe and band insulator PbTe which exhibits a nonsaturating
      linear magneto-resistance (MR) effect, a novel phenomenon widely observed in
      topological materials with gapless dispersion. It is shown that in the van der
      Pauw geometry in which the longitudinal and transverse magneto-resistances are
      measured to extract the magneto-conductivity, the two-band Drude model is not
      sufficient to self-consistently describe both the longitudinal and transverse
      magneto-conductivities. Furthermore, in the Corbino geometry, which directly
      measures the longitudinal magneto-conductivity sigma xx( B) for a straightforward
      comparison with the Drude model, the MR, 1/sigma xx( B), still reveals a large
      linear MR effect, in direct discrepancy with the Drude model. While shining
      further light on the multiple-carrier transport in TCI, this study highlights an
      unusual magneto-transport character of topological materials that challenges the
      standard Drude picture of electron transport.

PMID- 30185049
TI  - Doped Twisted Bilayer Graphene near Magic Angles: Proximity to Wigner
      Crystallization, Not Mott Insulation.
AB  - We devise a model to explain why twisted bilayer graphene exhibits insulating
      behavior when nu = 2 or 3 charges occupy a unit moire cell, a feature attributed
      to Mottness per previous work but not for nu = 1, clearly inconsistent with Mott
      insulation. We compute rs = EU/ EK, where EU and EK are the potential and kinetic
      energies, respectively, and show that (i) the Mott criterion lies at a density
      larger than experimental values by a factor of 104 and (ii) a transition to a
      series of Wigner crystalline states exists as a function of nu. We find that, for
      nu = 1, rs fails to cross the threshold ( rs = 37) for the triangular lattice,
      and metallic transport ensues. However, for nu = 2 and nu = 3, the thresholds rs
      = 22 and rs = 17, respectively, are satisfied for a transition to Wigner crystals
      (WCs) with a honeycomb (nu = 2) and a kagome (nu = 3) structure. We posit that
      such crystalline states form the correct starting point for analyzing
      superconductivity.

PMID- 30185050
TI  - All-Optical Mapping of the Position of Quantum Dots Embedded in a Nanowire
      Antenna.
AB  - Nanowire antennas embedding single quantum dots (QDs) have recently emerged as a
      versatile solid-state platform for quantum optics. Within the nanowire section,
      the emitter position simultaneously determines the strength of the light-matter
      interaction, as well as the coupling to potential decoherence channels.
      Therefore, to quantitatively understand device performance and guide future
      optimization, it is highly desirable to map the emitter position with an accuracy
      much smaller than the waveguide diameter, on the order of a few hundreds of
      nanometers. We introduce here a nondestructive, all-optical mapping technique
      that exploits the QD emission into two guided modes with different transverse
      profiles. These two modes are fed by the same emitter and thus interfere. The
      resulting intensity pattern, which is highly sensitive to the emitter position,
      is resolved in the far-field using Fourier microscopy. We demonstrate this
      technique on a standard microphotoluminescence setup and map the position of
      individual QDs in a nanowire antenna with a spatial resolution of +/-10 nm. This
      work opens important perspectives for the future development of light-matter
      interfaces based on nanowire antennas. Beyond single-QD devices, it will also
      provide a valuable tool for the investigation of collective effects that imply
      several emitters coupled to an optical waveguide.

PMID- 30185051
TI  - Tuning Lasing Emission toward Long Wavelengths in GaAs-(In,Al)GaAs Core
      Multishell Nanowires.
AB  - Semiconductor nanowire (NW) lasers are attractive as integrated on-chip coherent
      light sources with strong potential for applications in optical communication and
      sensing. Realizing lasers from individual bulk-type NWs with emission tunable
      from the near-infrared to the telecommunications spectral region is, however,
      challenging and requires low-dimensional active gain regions with an adjustable
      band gap and quantum confinement. Here, we demonstrate lasing from GaAs
      (InGaAs/AlGaAs) core-shell NWs with multiple InGaAs quantum wells (QW) and lasing
      wavelengths tunable from ~0.8 to ~1.1 MUm. Our investigation emphasizes
      particularly the critical interplay between QW design, growth kinetics, and the
      control of InGaAs composition in the active region needed for effective tuning of
      the lasing wavelength. A low shell growth temperature and GaAs interlayers at the
      QW/barrier interfaces enable In molar fractions up to ~25% without plastic strain
      relaxation or alloy intermixing in the QWs. Correlated scanning transmission
      electron microscopy, atom probe tomography, and confocal PL spectroscopy analyses
      illustrate the high sensitivity of the optically pumped lasing characteristics on
      microscopic properties, providing useful guidelines for other III-V-based NW
      laser systems.

PMID- 30185052
TI  - Direct Correlation of Carbon Nanotube Nucleation and Growth with the Atomic
      Structure of Rhenium Nanocatalysts Stimulated and Imaged by the Electron Beam.
AB  - Subnanometer Re clusters confined in a single-walled carbon nanotube are
      activated by the 80 keV electron beam to promote the catalytic growth of a new
      carbon nanotube. Transmission electron microscopy images the entire process step
      by-step, with atomic resolution in real time, revealing details of the initial
      nucleation followed by a two-stage growth. The atomic dynamics of the Re cluster
      correlate strongly with the nanotube formation process, with the growth
      accelerating when the catalyst becomes more ordered. In addition to the nanotube
      growth catalyzed by Re nanoclusters, individual atoms of Re released from the
      nanocluster play a role in the nanotube formation.

PMID- 30185053
TI  - Crystalline, Phononic, and Electronic Properties of Heterostructured Polytypic Ge
      Nanowires by Raman Spectroscopy.
AB  - Semiconducting nanowires (NWs) offer the unprecedented opportunity to host
      different crystal phases in a nanostructure, which enables the formation of
      polytypic heterostructures where the material composition is unchanged. This
      characteristic boosts the potential of polytypic heterostructured NWs for
      optoelectronic and phononic applications. In this work, we investigate cubic Ge
      NWs where small (~20 nm) hexagonal domains are formed due to a strain-induced
      phase transformation. By combining a nondestructive optical technique (Raman
      spectroscopy) with density-functional theory (DFT) calculations, we assess the
      phonon properties of hexagonal Ge, determine the crystal phase variations along
      the NW axis, and, quite remarkably, reconstruct the relative orientation of the
      two polytypes. Moreover, we provide information on the electronic band alignment
      of the heterostructure at points of the Brillouin zone different from the one
      (Gamma) where the direct band gap recombination in hexagonal Ge takes place. We
      demonstrate the versatility of Raman spectroscopy and show that it can be used to
      determine the main crystalline, phononic, and electronic properties of the most
      challenging type of heterostructure (a polytypic, nanoscale heterostructure with
      constant material composition). The general procedure that we establish can be
      applied to several types of heterostructures.

PMID- 30185054
TI  - Dealing with image shifting in 3D ToF-SIMS depth profiles.
AB  - The high sputter efficiency and low damage of gas cluster ion beams have enabled
      depth profiling to greater depths within organic samples using time-of-flight
      secondary ion mass spectrometry (ToF-SIMS). Due to the typically fixed geometry
      of the ion sources used in ToF-SIMS, as one digs into a surface, the position
      sampled by ion beams shifts laterally. This causes a lateral shift in the
      resulting images that can become quite significant when profiling down more than
      one micron. Here, three methods to compensate for this image shifting are
      presented in order to more accurately stack the images to present a 3D
      representation. These methods include (1) using software to correct the image
      shifts post-acquisition, (2) correcting the sample height during acquisition, and
      (3) adjusting the beam position during acquisition. The advantages and
      disadvantages of these methods are discussed. It was found that all three methods
      were successful in compensating for image shifting in ToF-SIMS depth profiles
      resulting in a more accurate display of the 3D data. Features from spherical
      objects that were ellipsoidal prior to shifting were seen to be spherical after
      correction. Software shifting is convenient as it can be applied after data
      acquisition. However, when using software shifting, one must take into account
      the scan size and the size of the features of interest as image shifts can be
      significant and can result in cropping of features of interest. For depth
      profiles deeper than a few microns, hardware methods should be used as they
      preserve features of interest within the field of view regardless of the profile
      depth. Software shifting can also be used to correct for small shifts not
      accounted for by hardware methods. A combination of hardware and software shift
      correction can enable correction for a wide range of samples and profiling
      depths. The scripts required for the software shifting demonstrated herein are
      provided along with tutorials in the supplementary material.

PMID- 30185055
TI  - Determination of total, free and esterified short-chain fatty acid in human serum
      by liquid chromatography-mass spectrometry.
AB  - Background Short-chain fatty acids are primarily absorbed through the portal vein
      during lipid digestion, which is utilized as the energy source, as well as
      prevent type 2 diabetes and some cancers. However, reports on the determination
      of these short-chain fatty acids in human serum are limited. Methods Blood
      samples from human subjects ( n = 547, male/female = 246/301, age 58.85 +/-
      12.57) were collected. Saponification was applied to obtain total fatty acid.
      After derivatization by 2-nitrophenylhydrazine, fatty acid 4:0 and fatty acid 6:0
      were measured by liquid chromatography-mass spectrometry. Results The developed
      method exhibited good linearity (R2 = 0.9996 for both). All the coefficients of
      variation of reproducibility and accuracy for fatty acid 4:0 and fatty acid 6:0
      ranged 3.0%-6.1%, with the average recoveries of 87.8%-102.4% and 92.2%-98.2%,
      respectively. In all the samples, the concentration of fatty acid 4:0 (162.4 +/-
      76.4 MUmol/L) was significantly higher than fatty acid 6:0 (2.0 +/- 2.5 MUmol/L,
      P < 0.001). Furthermore, the esterified form was predominant in both fatty acid
      4:0 and fatty acid 6:0 (98.2% and 82.4% of total fatty acids, respectively).
      Besides, short-chain fatty acids showed no significant differences with regard to
      sex or age differences. Conclusion This developed liquid chromatography-mass
      spectrometry method is convenient and reliable, which might be useful for
      monitoring the variations of short-chain fatty acids in blood.

PMID- 30185056
TI  - Big data in clinical biochemistry.

PMID- 30185057
TI  - Metabarcoding and metabolomics offer complementarity in deciphering marine
      eukaryotic biofouling community shifts.
AB  - Metabarcoding and metabolomics were used to explore the taxonomic composition and
      functional diversity of eukaryotic biofouling communities on plates with
      antifouling paints at two French coastal sites: Lorient (North Eastern Atlantic
      Ocean; temperate and eutrophic) and Toulon (North-Western Mediterranean Sea;
      mesotrophic but highly contaminated). Four distinct coatings were tested at each
      site and season for one month. Metabarcoding showed biocidal coatings had less
      impact on eukaryotic assemblages compared to spatial and temporal effects.
      Ciliophora, Chlorophyceae or Cnidaria (mainly hydrozoans) were abundant at
      Lorient, whereas Arthropoda (especially crustaceans), Nematoda, and Ochrophyta
      dominated less diversified assemblages at Toulon. Seasonal shifts were observed
      at Lorient, but not Toulon. Metabolomics also showed clear site discrimination,
      but these were associated with a coating and not season dependent clustering. The
      meta-omics analysis enabled identifications of some associative patterns between
      metabolomic profiles and specific taxa, in particular those colonizing the plates
      with biocidal coatings at Lorient.

PMID- 30185058
TI  - MTIS 2018 Author index.

PMID- 30185059
TI  - MTIS 2018 Abstracts.

PMID- 30185060
TI  - What Happens to Retirement Plans, and Does This Affect Retirement Satisfaction?
AB  - This study examines the role of planning and plan fulfillment for retirement
      satisfaction using a dynamic resource theory approach. A 3-year qualitative
      longitudinal design was deployed with interviews conducted first on the cusp of
      retirement, then 1 and 2 years after retirement. The final sample comprised 41
      individuals from England, 40 from Italy, and 30 from the United States. Realizing
      plans was found to be linked to retirement satisfaction. However, many retirees
      adjusted well to retirement without planning in advance, or when plans were
      thwarted, and sometimes retirement did not live up to expectations despite
      fulfillment of plans. Psychological resources and resilience were key dimensions
      of satisfaction regardless of planning. Retirement satisfaction was also
      associated with social integration, adoption of new social roles, and
      opportunities to be active within and beyond the private sphere, such as
      volunteering or participating in leisure oriented clubs or activities. Regardless
      of planning, the quality of family relationships was a particularly important
      element for retirement satisfaction or dissatisfaction.

PMID- 30185061
TI  - The localization of CD3, CD79a, CD68 and S100 protein immunoreactive cells in
      hemal nodes of Saanen goat (Capra hircus).
AB  - We investigated the structure of hemal nodes in Saanen goats using
      immunohistochemical staining. We examined the distribution of CD3 positive T
      lymphocytes, CD79a positive B lymphocytes, CD68 positive macrophages and S100
      protein positive follicular dendritic cells. Hemal nodes of six healty adult
      female goats were used. Hemal nodes were removed from the thoracic and abdominal
      cavities. The oval to round hemal nodes were observed especially between the
      abdominal aorta and vena cava, and near the kidneys and adrenal glands. Tissue
      sections were stained with Crossmon's modified triple stain to demonstrate
      general histological structure. The avidin-biotin-peroxidase technique using anti
      CD3, anti-CD79a, anti-CD68 and anti-S100 primary antibodies was used for
      immunohistochemistry. Many CD3 positive T lymphocytes were found in the germinal
      center of the lymph follicles and in the lymphatic cords of hemal nodes; CD3
      positive cells also were observed in the sinuses. CD79a and CD68 positive cells
      were found at the germinal center of the lymph follicles. In the lymph follicles
      near the subcapsular sinuses, CD79a and CD68 positive cells were found especially
      in e areas bordering the mantle zone. S100 positive cells were found in the lymph
      follicles, lymphatic cords and sinuses.

PMID- 30185062
TI  - Malignancy Trends in HIV-Infected Patients Over the Past 10 Years in a Single
      Center Retrospective Observational Study in the United States.
AB  - The introduction of antiretroviral therapy (ART) in 1995 had a dramatic impact on
      the morbidity and mortality of the HIV population, and subsequently, the natural
      history of cancer has changed. The purpose of our study was to review the
      prevalence of AIDS-defining malignancies and non-AIDS defining cancers (NADC),
      taking into consideration racial and gender variations. After the institutional
      review board approval, the study was conducted as a retrospective chart review of
      279 HIV-infected patients who were treated at the Moffitt Cancer Center between
      January 1, 2000 and December 31, 2010. The demographic characteristics included
      gender, ethnicity, race, presence or absence of ART, and the type of malignancy
      reviewed. Of 233 men, 78 (33.5%) had AIDS-defining malignancies. AIDS-related non
      Hodgkin lymphoma (NHL) was detected in 49 (21%) patients and Kaposi sarcoma (KS)
      in 29 (12%) patients. Two-thirds of male patients had NADC, with anal cancer
      being the most prevalent (8.5%), followed by Hodgkin lymphoma (6%). AIDS-related
      NHL was also the predominant malignancy for women with a prevalence of 19.5%
      followed by invasive cervical cancer (ICC) and breast cancer, both with a similar
      prevalence of 11%. Kaposi sarcoma and anal cancer were equally detected in 2% of
      women. The prevalence rates of AIDS-defining malignancies among those of white
      race were 34%, ranging from 21% for NHL to 13% for KS and 1.5% for ICC. Twenty
      one (7.7%) patients had anal cancer. AIDS-defining malignancies were found in 36%
      of patients of black race and 60% had NHL. Non-AIDS-related NHL was the second
      most common malignancy, followed by breast cancer and anal cancer with a similar
      prevalence of 6.5%. Of 279 patients, 53% were taking ART; 39.4% were not taking
      ART; and in 7.5% of the patients, it was unknown if they were taking ART. In the
      ART era, our study found NADC to be more prevalent than AIDS-defining
      malignancies with 60% versus 40%, respectively. Non-Hodgkin lymphoma remained the
      most common AIDS-related malignancy in both genders. Among the patients with
      NADC, anal cancer was the predominant malignancy. The increasing incidence of
      some of the NADC is expected as this population is living longer with chronic
      exposure of viral replication of virus with oncogenic potential such as Human
      papillomavirus (HPV), Hepatitis B virus (HBV), Epstein-Barr virus (EBV), and
      Human herpesvirus 8 (HHV-8). Early ART initiation, aggressive vaccination, and
      judicious cancer screening are the cornerstone of cancer prevention of this
      growing population.

PMID- 30185063
TI  - Assessment of 22 inorganic elements in human amniotic fluid: a cross-sectional
      study conducted in Canary Islands (Spain).
AB  - We conducted a cross-sectional study in the Hospital Universitario de Canarias
      (Tenerife, Canary Islands, Spain) measuring 22 inorganic elements in amniotic
      fluid (AF) samples obtained from 65 pregnant women. ICP-MS was used for
      quantification of inorganic elements. Newborn parameters at delivery were all
      within the normal range. Concentrations of all elements were detected in
      measurable amounts in AF. The concentration of elements was similar to those
      reported in the literature. The concentrations of the most dangerous heavy metals
      - Cd, Cr, Ni, Hg and Pb - were lower than those reported by other authors. This
      study demonstrates that toxic inorganic elements pass into and accumulate in AF.
      The presence of such pollutants in contact with developing embryos from the
      intrauterine period could exert adverse health effects that deserve future
      investigations.

PMID- 30185064
TI  - Effects of depression and exercise on health-related quality of life in patients
      with Parkinson's disease.
AB  - Objectives There is limited literature describing the effect exercise may have on
      depression and an individual's health-related quality of life (HRQoL) in
      Parkinson's Disease (PD). We aim to quantify this effect. Methods A cross
      sectional questionnaire was administered to 60 PD subjects. The Parkinson's
      Disease Questionnaire-39 (PDQ-39) summary index and the Geriatric Depression
      Scale-30 were used to quantify HRQoL and depression, respectively. Data were
      obtained on exercise habits. ANOVA and multivariate linear regression analysis
      were used to calculate mean differences in HRQoL. Results Depression was
      consistently related to HRQoL ( p < 0.05). Of those who exercised as an adult
      before PD diagnosis, 49.02% ( n = 25) reported depression as compared to 88.89% (
      n = 8) of those who did not report adult exercise ( p = 0.03). Those who
      exercised frequently as an adult prior to PD diagnosis had a better PDQ-39
      Cognitive Index ( p = 0.03). Those who were not depressed and were currently
      exercising had a significantly higher HRQoL than those who were depressed and did
      not exercise ( p < 0.01). Discussion Exercising and depression may interact to
      affect HRQoL. Thus, coordination of mental health evaluation and exercise
      regimens in persons with PD may improve HRQoL.

PMID- 30185065
TI  - Prevalence and diversity of blaTEM, blaSHV and blaCTX-M variants among multidrug
      resistant Klebsiella spp. from an urban riverine environment in India.
AB  - In the present study, we have investigated prevalence and diversity of ESBL genes
      among Klebsiella isolates obtained from highly polluted stretch of river Yamuna,
      India. Phenotypic screenings of 116 Klebsiella isolates revealed ~30% were
      positive for ESBL production. Antibiotic profiling showed multidrug resistance
      phenotype among 90% isolates. Prevalence of blaTEM, blaSHV and blaCTX-M genes
      were found to be 57, 54 and 48% respectively. Furthermore, we identified eight
      variants of blaSHV (SHV-1, SHV-11, SHV-27, SHV-28, SHV-38, SHV-61, SHV-144, SHV
      148), three each of blaTEM (TEM-1, TEM-116, TEM-206) and blaCTX-M (CTX-M-15, CTX
      M-55, CTX-M-188) among Klebsiella spp. Co-occurrence of blaTEM, blaSHV and blaCTX
      M (any two or all three) was observed among 45% Klebsiella isolates. Occurrence
      of blaCTX-M-188 and blaTEM-206 in environmental isolates of K. pneumoniae has not
      been reported earlier. Identification of blaTEM-206, blaSHV-27 and blaSHV-144
      from Klebsiella spp. and blaTEM-116 from K. quasipneumoniae and K. variicola is
      the first report from India.

PMID- 30185066
TI  - The protective effects of astaxanthin against cisplatin-induced retinal toxicity.
AB  - This study investigated the toxic effects of an antineoplastic agent, Cisplatin
      (CIS), on retinal cells and the potential capacity of Astaxanthin (ASTA) to
      elicit a future therapeutic protocol in CIS-induced retinal toxicity. Six groups
      were formed for the assessment; control (healthy; Group 1), olive oil (olive oil
      only; Group 2), ASTA control group (ASTA only, Group 3), the single
      intraperitoneal (IP) dose of 16 mg/kg CIS (CIS only group; Group 4), 16 mg/kg CIS
      + 25 mg/kg (IP) ASTA (Group 5) and 16 mg/kg CIS + 75 mg/kg (IP) ASTA (Group 6).
      On the third day after cisplatin administration, rats in all groups were
      sacrificed under anesthesia and the analysis of the biochemical parameters and
      histopathological levels were performed. A significant decrease in GSH levels and
      increases in MDA, eNOS, 8-OHdG expressions were recorded. Additionally, CIS
      treatment had caused acidophilic staining in retinal histological appearance.
      ASTA treatment reduced the increases in MDA, eNOS, and 8-OHdG levels following
      CIS administration and increased the levels of GSH expressions, as well. These
      results may suggest the ASTA molecule as a promising option to prevent retinal
      toxicity in patients receiving CIS treatment for malignant tumors.

PMID- 30185067
TI  - Comparison between inferior vena cava ultrasound, lung ultrasound, bioelectric
      impedance analysis, and natriuretic peptides in chronic heart failure.
AB  - BACKGROUND: Heart failure (HF) is an important healthcare problem. Knowing volume
      status in outpatients with chronic HF to adjust treatment and to avoid
      decompensations is a challenge. The aim of this study is comparing the usefulness
      of inferior vena cava (IVC) ultrasound, lung ultrasound, bioelectrical impedance
      analysis (BIA), and natriuretic peptides in the follow-up of outpatients with
      chronic HF. METHODS: This was a prospective cohort study. Ninety-nine patients
      with chronic HF were included consecutively as they attended scheduled medical
      visits. The different techniques were performed on the day of the clinic visit,
      and the result was hidden from the patients and the responsible medical team.
      Follow-up time was 1 year. Outcome events checked were a combination of death or
      hospitalization, due to HF. RESULTS: Thirty-six patients (36.4%) died or were
      hospitalized for HF. They had a significantly lower IVC collapse, and a greater
      number of lung B-lines and higher NTproBNP levels compared to patients who
      remained stable. There were no differences in the BIA parameters. After
      multivariable analysis, cut-off points of IVC collapse <30%, number of pulmonary
      B lines greater than 5, and NTproBNP levels greater than 2000 pg/ml were
      associated with increased risk of HF death or admission. NTproBNP had the best
      area under the curve. CONCLUSION: Evaluation of congestion in outpatients with
      chronic HF may be based on NTproBNP, IVC ultrasound, or lung ultrasound; they are
      useful in identifying patients at high risk of hospitalization or death due to
      HF.

PMID- 30185068
TI  - Exposure to low doses of UVA increases biofilm formation in Pseudomonas
      aeruginosa.
AB  - The establishment of bacterial biofilms on abiotic surfaces is a complex process
      regulated by multiple genetic regulators and environmental factors which are able
      to modulate the passage of planktonic cells to a sessile state. Solar ultraviolet
      A radiation (UVA, 315-400) is one of the main environmental stress factors that
      bacteria must face at the Earth's surface. The deleterious effects of UVA are
      mainly due to oxidative damage. This paper reports that exposure to low UVA doses
      promotes biofilm formation in three prototypical strains of Pseudomonas
      aeruginosa, a relevant opportunistic human pathogen. It demonstrates that
      exposure of planktonic cells to sublethal doses of UVA can increase cell surface
      hydrophobicity and swimming motility, two parameters known to favor cell
      adhesion. These results suggest that UVA radiation acts, at least in part, by
      promoting the first stages of biofilm development.

PMID- 30185069
TI  - Pharmacotherapeutic management of macular edema in diabetic subjects undergoing
      cataract surgery.
AB  - INTRODUCTION: Cataracts and diabetes are widespread pathologies that are of
      growing concern to the global population. In diabetic patients who have had
      cataract surgery, the worsening of preexisting diabetic macular edema or
      occurrence of pseudophakic cystoid macular edema are common causes of visual
      impairment even with the most advanced surgical techniques available today for
      phacoemulsification. Areas covered: In this review, the authors assess the
      available literature to evaluate and compare different drugs, with the aim of
      establishing the best pharmacological strategies for the prevention and treatment
      of macular edema in diabetic patients undergoing cataract surgery. Expert
      opinion: Guidelines for the optimal management of diabetic macular edema in
      conjunction with cataract surgery or treatment of pseudophakic cystoid macular
      edema in diabetic patients are still lacking. To treat these conditions,
      clinicians need to understand the pharmacokinetics, posology, and efficacy of
      available drugs: topical non-steroidal anti-inflammatory drugs (NSAIDs),
      intravitreal anti-vascular endothelial growth factors (VEGFs), and both topical
      and intravitreal steroids. Diabetic patients undergoing cataract surgery should
      receive topical NSAIDs to prevent pseudophakic cystoid macular edema.
      Intravitreal anti-VEGFs and steroids, in association with cataract surgery, are
      indicated for patients with preexisting diabetic macular edema or those at high
      risk of macular edema after surgery.

PMID- 30185070
TI  - Feasibility study using iodine quantification on dual-energy CT enterography to
      distinguish normal small bowel from active inflammatory Crohn's disease.
AB  - Background Assessment of Crohn's disease (CD) activity is important to identify
      patients with active inflammation for therapy management. Quantitative analysis
      can provide objective measurement of disease presence. Purpose To evaluate the
      feasibility of quantitative analysis of contrast-enhanced dual-energy computed
      tomography (DECT) data in detection of small bowel inflammation in patients with
      CD with an emphasis on iodine quantification. Material and Methods DECT
      enterography was prospectively performed in 20 patients with active CD and in 20
      healthy individuals, as the control group. Iodine overlay images were created.
      Wall thickness, attenuation, absolute iodine density, relative iodine density,
      and fat fraction were measured in the terminal ileum of all patients by two
      radiologists. Intraclass correlation coefficients were calculated to assess inter
      rater agreement. Parameters were compared between patient groups using mixed
      model analysis. Receiver operating characteristic (ROC) analysis was performed.
      Results Both absolute and relative iodine density were significantly higher in
      active disease than in normal small bowel (all P < 0.001). In contrast,
      measurement of fat fraction was not significantly different in affected terminal
      ileal loops compared to normal terminal ileum ( P = 0.075). ROC analysis
      demonstrated a similar excellent diagnostic accuracy of wall thickness,
      attenuation, and absolute and relative iodine density with area under the ROC
      curve (AUC) values in the range of 0.96 for attenuation to 1 for relative iodine
      density. Conclusion DECT with iodine quantification can be used in distinguishing
      normal small bowel from active inflammatory CD. Further research should
      investigate the value of iodine quantification in grading CD activity and in
      monitoring therapeutic response.

PMID- 30185071
TI  - Standardization of hippocampus volumetry using automated brain structure
      volumetry tool for an initial Alzheimer's disease imaging biomarker.
AB  - Background One significant barrier to incorporate Alzheimer's disease (AD)
      imaging biomarkers into diagnostic criteria is the lack of standardized methods
      for biomarker quantification. The European Alzheimer's Disease Consortium
      Alzheimer's Disease Neuroimaging Initiative (EADC-ADNI) Harmonization Protocol
      project provides the most authoritative guideline for hippocampal definition and
      has produced a manually segmented reference dataset for validation of automated
      methods. Purpose To validate automated hippocampal volumetry using AccuBrainTM,
      against the EADC-ADNI dataset, and assess its diagnostic performance for
      differentiating AD and normal aging in an independent cohort. Material and
      Methods The EADC-ADNI reference dataset comprise of manually segmented
      hippocampal labels from 135 volumetric T1-weighted scans from various scanners.
      Dice similarity coefficient (DSC), intraclass correlation coefficient (ICC), and
      Pearson's r were obtained for AccuBrainTM and FreeSurfer. The magnetic resonance
      imaging (MRI) of a separate cohort of 299 individuals (150 normal controls, 149
      with AD) were obtained from the ADNI database and processed with AccuBrainTM to
      assess its diagnostic accuracy. Area under the curve (AUC) for total hippocampal
      volumes (HV) and hippocampal fraction (HF) were determined. Results Compared with
      EADC-ADNI dataset ground truths, AccuBrainTM had a mean DSC of 0.89/0.89/0.89,
      ICC of 0.94/0.96/0.95, and r of 0.95/0.96/0.95 for right/left/total HV.
      AccuBrainTM HV and HF had AUC of 0.76 and 0.80, respectively. Thresholds of <=
      5.71 mL and <= 0.38% afforded 80% sensitivity for AD detection. Conclusion
      AccuBrainTM provides accurate automated hippocampus segmentation in accordance
      with the EADC-ADNI standard, with great potential value in assisting clinical
      diagnosis of AD.

PMID- 30185072
TI  - Palliative esophagectomy in unexpected metastatic disease: sense or nonsense?
AB  - Background Despite integrated positron emission tomography and computed
      tomography screening before and after neoadjuvant treatment in patients with
      locally advanced esophageal cancer, unexpected metastatic disease is still found
      in some patients during surgery. Should then esophagectomy be aborted or is there
      a place for palliative resection? Methods Between 2002 and 2015, 681 patients
      with potentially resectable esophageal cancer were sheduled for neoadjuvant
      therapy and subsequent esophagectomy. In 552 patients, a potentially curative
      esophagectomy was performed. In 12 patients, unexpected disease was discovered
      during surgery but esophagectomy was performed with synchronous resection of
      metastases; 10 of them had oligometastatic disease (<=4 single-organ metastases).
      Esophagectomy was not performed in 117 patients (because of disease progression
      in 50); 14 were also single-organ oligometastatic. Data of 10 single-organ
      oligometastatic patients who underwent esophageal resection (group 1) were
      compared those of 10 non-resected but treated counterparts (group 2) and with 228
      patients who underwent potentially curative esophagectomy with persistent
      pathological lymph nodes (group 3). Results Five oligometastatic esophagectomy
      patients had lung metastases: 1 peritoneal, 2 adrenal, 1 pleural, and 1
      pancreatic. Two oligometastatic non-resected patients had lung, 5 liver, and 3
      brain metastases. Median overall survival was 21.4, 12.1, and 20.2 months in the
      respective groups (group 1 vs. group 2  p = 0.042; group 2 vs. group 3  p =
      0.002; group 1 vs. group 3  p = 0.88). Conclusions Survival is longer in patients
      undergoing palliative esophagectomy with unexpected single-organ oligometastatic
      disease and comparable to survival in patients with persistent pathological lymph
      nodes. Palliative resection in these patients seems to be justified.

PMID- 30185073
TI  - Mycobacterial granuloma on the staple line after pulmonary resection.
AB  - Objective It has been reported previously that granulomas can occur around
      nonabsorbable sutures, but that granuloma formation around the staple line is
      very rare. However, the increased use of thoracoscopic surgery is creating more
      opportunities to use automatic mechanical suturing equipment for pulmonary
      surgery, and it is expected that the incidence of granuloma around the staple
      line will increase. Methods We retrospectively investigated the clinical records
      of 6 patients who developed nontuberculous mycobacterial granuloma on the staple
      line after pulmonary resection. We investigated their clinical characteristics
      and compared them with data in 16 cases of cancer recurrence. Results
      Fluorodeoxyglucose uptake was detected in all 6 patients. Laboratory data
      including white blood cell counts and C-reactive protein levels were within
      normal ranges in all patients. There was no evident tendency in terms of age,
      sex, maximal standardized uptake value, or radiological findings. However,
      compared to cancer recurrence, mycobacterial granuloma around the staple line
      appeared after a longer period of time, and the proportion of patients who had a
      segmentectomy as the initial surgery was significantly higher. Conclusion When
      growing shadows are observed near the staple line, it is difficult to
      differentiate between cancer recurrence and nontuberculous mycobacterial
      granuloma from computed tomography and laboratory findings. However, if a mass
      shadow around the staple line appears 2, 3, or more years after segmentectomy, it
      could be considered likely to be a granuloma. "Post-segmentectomy" and "late
      occurrence" are important attributes for distinguishing staple line granuloma
      from cancer recurrence.

PMID- 30185075
TI  - Spherical right atrial thrombus with a fibrous capsule and stalk.

PMID- 30185074
TI  - Predictors of surgical outcome in isolated prosthetic mitral valve endocarditis.
AB  - Background Most previous studies dealing with predictors of surgical outcome in
      prosthetic valve endocarditis included patients with aortic and/or mitral valve
      prostheses. Here, we concentrate on isolated prosthetic mitral endocarditis due
      to heterogeneity of epidemiological data, anatomical factors, and surgical
      techniques between mitral, prosthetic mitral, and aortic endocarditis between
      prosthetic mitral and prosthetic aortic endocarditis. Methods Data of 40 patients
      reoperated upon due to isolated prosthetic mitral endocarditis between July 2015
      and March 2017 were retrospectively collected and analyzed. Results Independent
      predictors of major postoperative complications on multivariate analysis were: no
      blood cultures before referral (odds ratio 6.36, 95% confidence interval: 1.44
      28.15), inadequate response to medical treatment (odds ratio 11.38, 95%
      confidence interval: 1.29-100.25), and serum creatinine >=2.0 mg.dL-1 (odds ratio
      4.56, 95% confidence interval: 1.07-19.36). Independent predictors of hospital
      mortality were: congestive heart failure (odds ratio 30.91, 95% confidence
      interval: 2.02 to 473.87), embolization (odds ratio 18.24, 95% confidence
      interval:1.94-171.91), peri-annular extension of infection (odds ratio 12.68, 95%
      confidence interval: 1.30-123.43), serum creatinine on admission > 2 mg.dL-1
      (odds ratio 9.67, 95% confidence interval: 1.97-47.48), and early prosthetic
      valve endocarditis (odds ratio 7.80, 95% confidence interval: 1.35-45.00).
      EuroSCORE II > 5.93% was associated with the highest predictive value for
      hospital mortality (area under the curve 0.813). Conclusion Certain factors can
      predict morbidity and mortality in surgery for isolated mitral prosthetic valve
      endocarditis. EuroSCORE II has a good ability to predict hospital mortality in
      surgery for mitral prosthetic valve endocarditis.

PMID- 30185076
TI  - Creating a personalized evaluation framework for patient-reported outcomes: an
      illustration using the EQ-5D visual analogue scale.
AB  - BACKGROUND: This paper outlines the creation of an intuitive, personalized
      evaluation framework for Patient-Reported Outcomes, using the EQ-5D visual analog
      scale (VAS) as an illustration. METHODS: A draft framework asked patients to
      divide and label the EQ-5D-VAS into different levels or categories of health.
      Comprehension of the framework and patient-defined health level labels, and how
      they map onto the EQ-5D-VAS, were tested through in-person, semi-structured
      interviews with individuals self-reporting cardiovascular disease. Interviews
      were conducted in three waves, with the framework revised between waves. RESULTS:
      Analyses included 14 participants. Eight participants (57.1%) felt that four
      levels of health were appropriate and there was general agreement on the labels;
      Poor, Fair, Good, and Excellent. There was substantial variability in where
      patients drew lines to indicate the level boundaries; Poor ranged between 0 and
      50; Fair 10-75; Good 40-91; Excellent 60-100. In wave 3, all participants
      demonstrated appropriate comprehension of the framework. CONCLUSIONS: The
      framework was well understood. The wide range of margins and the extent of
      overlap between the levels provide strong evidence for the relevance of the
      personalized evaluation framework approach, and specifically a personalized EQ-5D
      VAS evaluation framework, to better understand and interpret each individual's
      response to the item.

PMID- 30185077
TI  - New guidelines for the diagnosis and treatment of neurocysticercosis: a difficult
      proposal for patients in endemic countries.
AB  - INTRODUCTION: Recent guidelines for the diagnosis and treatment for
      neurocysticercosis (NC) from the Infectious Disease Society of America/American
      Society of Tropical Medicine and Hygiene were developed to be used in the United
      States and Canada, where only a small fraction of NC cases occur. Areas covered:
      The paper discusses the strengths and weakness of the proposed guidelines. Expert
      commentary: Although these new guidelines bring much needed attention to a
      neglected parasitic disease, some of the recommendations made are based on
      insufficient and/or inadequate evidence. The authors only recommend one specific
      immunological assay for use in the diagnosis of NC, when evidence clearly
      supports other options. The authors strongly recommend dual-anthelminthic for
      patients with multiple active parenchymal cysts on the basis of one clinical
      trial that was stopped early. The authors recommend surgical removal of cysts in
      the fourth ventricle and long-term treatment for subarachnoid NC despite their
      own admission that there is little evidence to support these recommendations. We
      propose that clinicians should approach some of the recommendations in the new
      guidelines with caution and call for the establishment of gold-standard
      guidelines that can be used and adapted for the diagnosis and treatment of
      patients with NC worldwide.

PMID- 30185078
TI  - The association of ghrelin, leptin, and insulin levels in umbilical cord blood
      with fetal anthropometric measurements and glucose levels at birth.
AB  - OBJECTIVES: To investigate the association of ghrelin, leptin, and insulin levels
      in the umbilical cord blood of the preterm and term infants with anthropometric
      measurements and glucose metabolism. METHODS: Sixty-nine infants who were born
      between November 2004 and June 2005 were included in the study. Pregnancy ages,
      birth weights, heights, head circumferences, and Ponderal Indexes (PI) were
      identified. Ghrelin, leptin, insulin, and glucose levels in the umbilical cord
      blood were studied. RESULTS: Eighteen infants out of 69 infants were preterm
      (34.6 +/- 0.43 weeks), and 33 infants were term (38.7 +/- 0.14 weeks). All
      preterm infant weights were appropriate for gestational age (AGA); 33 of the term
      infants' weights were AGA and 18 were large for gestational age (LGA). Leptin,
      insulin, and glucose levels of term infants were significantly higher compared
      with the preterm infants (p < .0001, p < .001, and p < .0001, respectively); no
      significant difference was detected in the ghrelin levels between the two groups
      (p > .05). The leptin and insulin levels of the term LGA infants were higher
      compared with the term AGA and preterm AGA infants (p < .05, for all). No
      difference was detected between the three groups regarding serum ghrelin levels
      (p > .05). No difference was found in the glucose levels between term AGA and LGA
      infants (p > .05); however, the serum glucose levels of term AGA and LGA infants
      were higher compared with levels in preterm AGA infants (p < .05, for both). A
      positive correlation was demonstrated in all study groups between leptin and
      insulin with gestational age, body weight, height, head circumference, and PI. A
      positive correlation was found between serum leptin levels with gestational age
      and insulin levels in preterm infants, and between serum leptin levels and
      insulin and glucose levels in term infants. No association was found between
      ghrelin and anthropometric measurements, leptin, insulin, and glucose levels (p >
      .05, for all). CONCLUSIONS: The increase of leptin production with increased
      gestational age, and the strong association with anthropometric measurements
      supports the opinion that leptin behaves as a fetal growth factor. Leptin in
      intrauterine life is in close association with insulin and glucose metabolism.
      Although ghrelin was at measurable levels in preterms, no association with fetal
      growth and glucose metabolism could be demonstrated in preterm and term infants.

PMID- 30185079
TI  - Chaperone-mediated autophagy as a therapeutic target for Parkinson disease.
AB  - INTRODUCTION: Parkinson disease (PD) is the most common neurodegenerative
      movement disorder. Currently only symptomatic treatments exist for PD, and so the
      search for potential neuroprotective drug targets is of great importance.
      Chaperone mediated autophagy (CMA) is one of the key cellular mechanisms in
      protein homeostasis. Many of the pathogenic pathways thought to be important in
      PD converge on CMA, thus rendering it an attractive therapeutic target. Areas
      covered: In this review we discuss current up-to-date knowledge of the molecular
      mechanisms involved in CMA function and regulation. We go on to discuss the links
      between CMA and PD including CMA's role in alpha-synuclein processing, oxidative
      stress, and mitochondrial function. We finish by exploring the potential benefits
      of how upregulation of CMA may be beneficial in PD and strategies to achieve
      this. Expert opinion: Upregulation of CMA is an attractive therapeutic target in
      PD due to its links with several pathogenic pathways . Currently more knowledge
      of the mechanisms that regulate CMA is required to allow for the development of
      specific CMA modulators. However, recent studies demonstrating the role of
      retinoic acid derivatives and miRNAs in regulating CMA are promising, and
      indirect upregulation of CMA by modulating other lysosomal pathways may be
      helpful.

PMID- 30185080
TI  - Retrospective cohort study of prenatally and postnatally diagnosed coarctation of
      the aorta (CoA): prenatal diagnosis improve neonatal outcome in severe CoA.
AB  - INTRODUCTION: Prenatal diagnosis of congenital heart disease (CHD) leads to
      improved outcome but not mortality rate. This may not be the case for coarctation
      of the aorta (CoA). The objective of this study is to estimate the effect of a
      prenatal diagnosis of CoA by comparing neonates with CoA by the time of
      diagnosis. MATERIALS AND METHODS: The study included 38 neonates with CoA
      diagnosed prenatally and 102 neonates diagnosed postnatally. The postnatal group
      was divided into two subgroups: (1) severe CoA: symptoms of CoA within the first
      7 days (n = 43) and (2) mild CoA: symptoms within the 8-28th day (n = 34). The
      neonates diagnosed more than 28 days after delivery were excluded from the study
      (n = 25). Severe CoA was defined as CHD diagnosed postnatally with clinical
      symptoms that presented in the first week after birth. Mild CoA was defined as
      CHD that presented clinical symptoms later than 7 days of life. RESULTS:
      Prostaglandins were initiated at lower doses (p < .001) in the prenatal group.
      Severe postnatal CoA was associated with more frequent Neonatal Intensive Care
      Unit (NICU) visits than mild postnatal CoA (p = .005). The length of
      hospitalization of neonates with severe postnatal CoA was 10 days longer than
      compared to the prenatal group, but the difference was not statistically
      significant. The highest mortality rate was in the severe postnatal CoA group
      (18.6%) which was significantly higher than the mortality rate in the prenatal
      group (p = .005). CONCLUSION: 1. Prenatal identification of fetuses at increased
      risk of developing CoA may reduce mortality and improve outcome only in neonates
      with severe CoA (symptoms of CoA within the first 7 days after birth); 2.
      Prenatal diagnosis of severe CoA was associated with lower prostaglandin doses
      and lower mortality rate.

PMID- 30185081
TI  - A review of application of stem cell therapy in the management of congenital
      heart disease.
AB  - Research on stem cells has been rapidly growing with impressive breakthroughs.
      Although merely a few of the laboratory researches have successfully transited to
      the clinical trial phase, the application of stem cells as a therapeutic option
      for some currently incapacitating diseases hold fascinating potentials. This
      review emphasis the various opportunities for the application of stem cell in the
      treatment of fetal diseases. First, we provide a brief commentary on the common
      stem cell strategy used in the treatment of congenital anomalies, thereafter we
      discuss how stem cell is being used in the management of some fetal disorders.

PMID- 30185082
TI  - The sigma-2 (sigma-2) receptor: a review of recent patent applications: 2013
      2018.
AB  - INTRODUCTION: The discovery of the sigma-2 receptor and the analogous sigma-1
      receptor led to a decade-long quest to determine the true nature of this protein
      and novel ligands capable of modulating its activity. Despite this challenge, the
      sigma-2 receptor has been linked to several disease states, and multiple classes
      of sigma-2 ligands have been published in the 40+ years since its initial
      discovery. Areas covered: This review covers newly published patent applications
      that describe sigma-2 receptor ligands capable of modulating disease states. The
      aforementioned documents entered the public domain as PCT patent applications
      between 2013 and 2018. Expert opinion: In 2017, the sigma-2 receptor was
      positively identified as TMEM97 (transmembrane protein 97). The resolution of
      this 'identity crisis' will facilitate a greater understanding of the
      pharmacological role of sigma-2 receptor as well as support the identification of
      novel sigma-2 receptor ligands with potential utility as disease-modifying
      therapies.

PMID- 30185083
TI  - Effectiveness and impact of the 10-valent pneumococcal conjugate vaccine, PHiD
      CV: review of clinical trials and post-marketing experience.
AB  - INTRODUCTION: Pneumococcal diseases (including septicemia, meningitis, pneumonia,
      and upper respiratory infections) constitute a major public health problem. The
      World Health Organization recommends pneumococcal conjugate vaccine immunization
      of young children worldwide. Areas covered: We reviewed evidence on the effects
      of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D
      conjugate vaccine (PHiD-CV), which is used in childhood immunization programs in
      over 45 countries or regions. The effectiveness of PHiD-CV against invasive
      pneumococcal disease (IPD), pneumonia, and acute otitis media was assessed. We
      also present its effect on pneumococcal nasopharyngeal carriage (NPC) and
      indirect effects (herd protection) among unvaccinated individuals. Expert
      commentary: Results from randomized, double-blind trials and post-marketing
      studies in various countries provide evidence of the protective efficacy,
      effectiveness, and impact of PHiD-CV against pneumococcal diseases. Data from
      different geographic locations also show reductions in NPC of vaccine
      pneumococcal serotypes, laying the foundation for indirect protection against
      pneumococcal disease. In countries where PHiD-CV is included in childhood
      immunization programs, there are signs of herd protection for vaccine serotypes
      among unvaccinated individuals. Although increases in non-vaccine serotype IPD
      and NPC rates were observed, there was an overall reduction of pneumococcal
      disease.

PMID- 30185084
TI  - Two-year postnatal outcome of 263 cases of fetal ventriculomegaly.
AB  - OBJECTIVES: To find out the outcome of fetal ventriculomegaly (VM) in terms of
      survival at birth and after two years and to evaluate the antenatal factors which
      influence the postnatal outcome. METHOD: We performed a 10-year prospective,
      observational study (2008-2018) including all prenatally detected fetal VM. Two
      years follow up of all live born was done to observe their survival, physical
      morbidity, and developmental delay. RESULTS: Fetal VM was seen in 263/648 (40.6%)
      cases with central nervous system malformation. VM was severe in 85.9% and was
      associated with other anomalies in 56.3% of the cases. Total 40.3% cases with VM
      were live born. The outcome at birth and was poorest with severe VM (40.7%) and
      when VM was associated with multiple defects (30%). Only 23.6% survived beyond
      two years of age. There was developmental delay in 24.2% cases. Logistic
      regression showed that, the presence of associated defect and severe VM were
      significant poor prognostic factors for survival at birth (p = .001) and after
      two years of age (p = .002). CONCLUSIONS: In a low resource setup the problems
      associated with fetal VM were compounded by late referral. The knowledge of the
      outcome in existing setup provides data for realistic counselling to the couple.

PMID- 30185085
TI  - TNF-alpha-induced oxidative stress and endothelial dysfunction in EA.hy926 cells
      is prevented by mate and green coffee extracts, 5-caffeoylquinic acid and its
      microbial metabolite, dihydrocaffeic acid.
AB  - The main phenol in mate and coffee, 5-caffeoylquinic-acid (5-CQA), and its
      relevant microbial metabolites, dihydrocaffeic (DHCA) and dihydroferulic (DHFA)
      acids, have shown oxidative-stress protective effects in HepG2 cells. To evaluate
      possible endothelial-protective effects of the extracts and compounds,
      endothelial EA.hy926 cells were pre-treated with yerba mate (YME) and green
      coffee bean (GCBE) phenolic extracts, 5-CQA, DHCA and DHFA and afterwards
      stressed with tumour-necrosis-factor-alpha (TNF-alpha). Then oxidative-stress
      markers and endothelial-nitric-oxide-synthase levels were studied. TNF-alpha (10
      ng/mL, 24 h) depleted reduced glutathione (GSH) and eNOS levels, increased
      reactive oxygen species (ROS) production, glutathione peroxidase (GPx) and
      reductase (GR) activities, and protein oxidation (carbonyl groups, CG) in
      EA.hy926 cells. Pre-treatment with YME, GCBE, 5-CQA, DHCA at certain
      physiological concentrations, lowered ROS production, recovered depleted GSH,
      reduced GR and GPx activities, and CG levels, and enhanced eNOS concentration..
      YME, GCBE and 5-CQA show antioxidant effects in endothelial cells playing DHCA an
      important role in such protection; moreover, the extracts, 5-CQA, DHCA and DHFA
      increased eNOS levels.

PMID- 30185086
TI  - Clinical characteristics, prognosis, and its risk factors of anorectal
      malformations: a retrospective study of 332 cases in Anhui Province of China.
AB  - OBJECTIVE: To analyze the clinical characteristics and prognosis of anorectal
      malformations (ARMs) and explore the influencing factors of postoperative anal
      function in Anhui Province of China. METHODS: We performed a retrospective study
      of ARM patients diagnosed from 2013 to 2016 at Anhui Provincial Children's
      Hospital. A total of 332 infants with ARM were enrolled in the survey.
      Demographic characteristic and clinical data were collected. Follow-up study was
      required to evaluate anal function after the operation and Logistic regression
      analysis was used for analyzing the influencing factors of prognosis. RESULTS: A
      total of 253 males and 79 females were studied, with a ratio of 3.2:1. Abdominal
      distention was the most common presenting symptom, followed by vomiting. Of the
      cases, 53.0% (176/332) combined with other congenital malformations. The
      incidence of other malformations in intermediate and high ARM group was
      significantly higher than that in the low ARM group. Of the cases, 280 underwent
      anoplasty. 188, 73, 19 cases were treated with one-stage perineal anoplasty,
      posterior sagittal anorectoplasty, laparoscopically assisted anorectal pull
      through, respectively. The result of follow-up study showed that the excellent
      and good rate of postoperative anal function was up to 83.3%. Type of ARM,
      combined with other malformations and the times of anoplasty were related to the
      anal function postoperatively. CONCLUSIONS: ARM occurs mainly in male infants.
      The incidence of associated abnormalities in ARM patients was high. Intermediate-
      and high-type, combined with other malformations and more times of anoplasty
      increased the risk of anal dysfunction postoperatively. Multicenter, prospective
      randomized-controlled studies were needed to clarify the curative effect of
      different surgical approaches.

PMID- 30185088
TI  - Exposure to tobacco use in pregnancy and its determinants among sub-Saharan
      Africa women: analysis of pooled cross-sectional surveys.
AB  - BACKGROUND: Tobacco use in any form and exposure to second-hand smoking are major
      threat to human health globally. Worse still, it is an important threat to the
      health of pregnant women and their children. However, the prevalence of tobacco
      use among pregnant women in sub-Saharan Africa countries remains uncertain. This
      study assessed the prevalence and factors of tobacco use among pregnant women in
      sub-Saharan Africa countries. METHODS: This study utilized data from Demographic
      and Health Surveys (DHS) conducted in 31 sub-Saharan Africa countries between
      2008 and 2017, comprising 44,715 pregnant women (aged 15-49 years). We calculated
      sampling weights to account for differentials in probabilities of selection and
      estimated proportions and 95% CIs for tobacco use in pregnant women across
      various countries. The factors associated with tobacco use were examined using
      multivariable binary logistic regression models at a significant level of 5%.
      RESULTS: Prevalence of tobacco use among pregnant women was ~2%. In Madagascar,
      the prevalence of tobacco use was 11.0%, while Lesotho (5.4%), Sierra Leone
      (4.8%), Namibia (4.4%) and Burundi (4.2%) were among the leading countries with
      high tobacco use pregnancy. The results of multivariable binary logistic
      regression model showed that pregnant women aged 25-34 years and >=35 years were
      2.26 times (OR = 2.26; 95%CI: 1.23, 4.15) and 2.45 times (OR = 2.45; 95%CI: 1.10,
      5.45) as likely to use tobacco products, compared to women aged <=24 years. The
      religious beliefs of pregnant women, who belong to other religion besides Islam,
      were 2.26 times as likely to use tobacco products compared to Christian women (OR
      = 2.26; 95%CI: 1.19, 4.31). In addition, pregnant women from households with
      middle-class wealth index had 64% reduction in tobacco products use among
      pregnant women, compared to those from poor households (OR = 0.36; 95%CI: 0.15
      0.87). CONCLUSION: Overall, tobacco use in pregnant women in sub-Saharan Africa
      was low; however high prevalence estimates were noted in some countries.
      Prevention and management of tobacco use and exposure to second-hand smoke during
      pregnancy is crucial to protect maternal and child health in Africa continent.
      Pregnant women should be examined about their tobacco use preferably with a
      biochemical test and those who use tobacco products be encouraged to use
      cessation supports such as nicotine replacement therapy (NRT) where available.
      Health professionals should identify tobacco products users and advise to quit,
      most importantly by offer cessation support. When tobacco products users become
      pregnant, the health benefits of cessation of tobacco use should be well
      discussed with them especially during antenatal care. The tobacco use of other
      members of the household is also crucial, as having a user partner could widely
      predict the exposure of a pregnant woman.

PMID- 30185087
TI  - An update on the use of anticoagulant therapy in ST-segment elevation myocardial
      infarction.
AB  - INTRODUCTION: Together with antiplatelet therapy, anticoagulants are vital to
      improve outcomes in patients presenting with ST-segment elevation myocardial
      infarction. Challenges lie in finding the optimal balance between the risk of
      bleeding and preventing thrombotic complications such as reinfarction or stent
      thrombosis. During the last decade, bivalirudin was introduced as a valid
      alternative to heparin for patients undergoing primary percutaneous coronary
      intervention. Several trials have been conducted to identify the agent with the
      best antithrombotic results at the lowest bleeding complication rate. In a
      rapidly evolving field with changes in vascular access, available P2Y12
      inhibitors, and indications for glycoprotein IIb/IIIa inhibitor administration,
      conflicting evidence became available. Areas covered: This paper mainly focuses
      on the evidence above and gives brief discussion to the recent literature on
      anticoagulation in fibrinolytic therapy and advances in antiplatelet therapy.
      Expert opinion: To date, no robust evidence is available challenging
      unfractionated heparin as the primary choice for anticoagulation in patients
      presenting with ST-segment elevation myocardial infarction. Further research
      should include efforts to refine anticoagulation strategies on an individual
      patient level. For patients undergoing primary percutaneous coronary
      intervention, bivalirudin could be used as an alternative to unfractionated
      heparin, while enoxaparin or fondaparinux is an alternative agent for patients
      treated with fibrinolytic therapy.

PMID- 30185090
TI  - Verrucous Carcinoma Arising in Association With Giant Condyloma.

PMID- 30185089
TI  - Cyclophosphamide versus cyclosporine A therapy in steroid-resistant nephrotic
      syndrome: a retrospective study with a mean 5-year follow-up.
AB  - OBJECTIVE: To compare the clinical efficacy of cyclophosphamide (CTX) and
      cyclosporine A (CSA) in initial treatment of children with steroid-resistant
      nephrotic syndrome (SRNS). METHODS: Prospectively maintained databases were
      reviewed to retrospectively compare two cohorts with SRNS that received peroral
      administration of 2 to 2.5 mg/kg/d CTX for 3 to 6 months or 1 to 5 mg/kg/d CSA
      for 2 years until the primary analysis cut-off date during 2007 to 2011. The time
      to first on-study relapse of SRNS was the primary endpoint. The effective rate
      was the second endpoint. RESULTS: A total of 127 children with SRNS were included
      (CTX-treated cohort: n = 62; CSA-treated cohort: n = 65), with a mean 5-year
      follow-up. CTX-treated children showed a significantly delayed time to first on
      study relapse of SRNS compared with CSA-treated children (hazard ratio 0.66, 95%
      confidence interval 0.32-1.75). The relapse rate (rate/year) in CTX-treated
      children (1.1 +/- 0.1) at the 24-month follow-up was significantly higher than
      that with CSA (0.4 +/- 0.2). This difference persisted until the final follow-up.
      CONCLUSIONS: CSA is associated with a significantly lower relapse rate and
      significantly higher effective rate compared with CTX, especially in children
      with minimal change disease.

PMID- 30185091
TI  - Exertional dyspnea after myocardial infarction: thinking beyond the diagnosis of
      heart failure.
AB  - INTRODUCTION: We herein present an unusual case of a pseudoaneurysm of the left
      ventricular myocardium, which is a rare and fatal complication of myocardial
      infarction. CASE REPORT: A 64-year-old man with a history of bipolar disorder and
      arterial hypertension was hospitalized for delayed presentation ST-elevation
      myocardial infarction. He was admitted to our hospital 24 hours after symptom
      onset. Diagnostic coronary angiography revealed 95% stenosis at the distal third
      of the right coronary artery, and he underwent a primary percutaneous coronary
      intervention to the culprit lesion. Despite administration of a diuretic and
      optimization of other pharmaceutical treatment, his heart failure deteriorated.
      Electrocardiography showed a sinus rhythm with Q-wave formation in the inferior
      wall leads (II, III, aVF), T-wave inversion in the same leads, and borderline QT
      prolongation (QTc of 490 ms). No ST elevation suggestive of left ventricular
      aneurysm formation was noticed. Forty days later, cardiac ultrasound revealed a
      dyskinetic cavity (pseudoaneurysm) in continuity with the posterior-inferior wall
      of the myocardium, resulting in severe mitral valve regurgitation. Unfortunately,
      the patient died while awaiting surgical treatment. CONCLUSION: Although most
      patients with left ventricular pseudoaneurysm have a relatively benign outcome,
      those with symptoms of heart failure must be urgently diagnosed and treated.

PMID- 30185092
TI  - Outcomes associated with trial of labor after cesarean in women with one versus
      two prior cesarean deliveries after a change in clinical practice guidelines in
      an academic hospital.
AB  - OBJECTIVE: In 2010, the American College of Obstetricians & Gynecologists (ACOG)
      published a new clinical practice guideline on trial of labor after cesarean
      (TOLAC) that was considered less restrictive. It allowed for offering TOLAC to
      women with two prior cesarean deliveries, even without a prior vaginal delivery,
      and for labor induction. As a result, our hospital, a public tertiary care
      academic center, updated our TOLAC practice guideline to reflect ACOG's new
      recommendations. We thus aim to evaluate maternal and neonatal outcomes for women
      undergoing TOLAC with 1 versus 2 prior cesareans, with and without a prior
      vaginal delivery, following these clinical practice changes at our hospital.
      STUDY DESIGN: This was a secondary analysis of a 2-year retrospective cohort
      following implementation of a hospital guideline in women undergoing TOLAC with a
      live, cephalic, singleton without lethal anomaly >= 24 0/7 weeks and 1 or 2 prior
      cesarean deliveries. Maternal and neonatal outcomes in women with one prior
      cesarean were compared to women with two prior cesareans. The primary outcome was
      composite maternal morbidity (uterine rupture, uterine dehiscence, hysterectomy,
      transfusion, postpartum venous thromboembolism, delivery/surgical injury,
      chorioamnionitis or endometritis, shoulder dystocia, death). Secondary outcomes
      included neonatal morbidity. Analysis was performed in SAS; p < 0.05 was
      considered significant. RESULTS: Seven hundred women with one prior cesarean and
      73 women with two prior cesareans underwent TOLAC after the 2011 guideline
      implementation. Postguideline maternal demographics, labor length, comorbid
      conditions, simplified Bishop score and induced labor were similar between
      groups. Composite maternal morbidity was similar between groups (18.3 versus
      23.3%, p = 0.30 for women with 1 versus 2 prior cesarean deliveries,
      respectively). The same was true when comparing women with 1 versus 2 prior
      cesareans who had never had a prior vaginal delivery (25.5 versus 33.3%, p = 0.28
      for 1 versus 2 prior cesarean deliveries, respectively). There were no
      differences in neonatal outcomes. Vaginal birth after cesarean (VBAC) success
      rates were similar between groups (78.9% in women with 1 prior cesarean versus
      74.0% in women with 2 prior cesareans, p = 0.33), even when only analyzing women
      without a prior vaginal delivery (69.4% in women with 1 prior cesarean versus
      71.4% in women with 2 prior cesareans, p = 0.78). CONCLUSION: Adoption of ACOG's
      TOLAC practice changes, specifically offering TOLAC to women with two prior
      cesareans even without a prior vaginal delivery, and offering induction of labor
      regardless of cervical favorability, may increase VBAC rates without increasing
      maternal or neonatal morbidity from TOLAC.

PMID- 30185093
TI  - Serum neuron-specific enolase, a marker of neuronal injury, increases after
      catheter ablation of atrial fibrillation.
AB  - OBJECTIVE: Catheter ablation of atrial fibrillation (AF) can lead to
      thromboembolic complications, especially stroke. We measured the periprocedural
      serum neuron-specific enolase (NSE) level, which is a biomarker of neuronal
      injury, after ablation of AF. METHODS: Forty-three patients with paroxysmal AF
      were prospectively enrolled before radiofrequency ablation. A neurological
      examination was performed before and after the procedure. The serum NSE level was
      determined before and at the end of the procedure and at 2, 24, and 48 h after
      the procedure. RESULTS: No patients developed new neurological deficits. However,
      the median (interquartile range) NSE level increased after ablation from 6.7
      (3.87) ng/mL at baseline to 11.48 (5.3) ng/mL at 24 h postoperatively. The NSE
      level exceed the upper reference limit of normal (17 ng/mL) in 14 patients (33%),
      and these patients were found to have a larger left atrium. CONCLUSIONS: Serum
      NSE increased in most of the patients undergoing ablation for AF, and it exceeded
      the normal limit in one-third of the patients. Although NSE is a biomarker of
      neuronal injury, the clinical importance of this increase after AF ablation and
      its relationship with the left atrial diameter should be evaluated in a
      longitudinal study.

PMID- 30185094
TI  - Non-Fatal Intoxication with a High Dose of Citalopram in a Suicidal 14-Year-Old
      Girl.
AB  - The use of selective serotonin reuptake inhibitors (SSRIs) like citalopram in the
      clinical treatment of depressive symptoms in children and adolescents has become
      increasingly common, although application is mostly off-label. The increasing
      number of prescriptions is not only due to their good efficacy, but also due to
      their good tolerability and the comparatively low risk in cases of intoxication.
      However, there is discussion about the cardiac safety of overdose ingestion of
      citalopram. Here, we report in detail on an adolescent with depressive symptoms
      who used 800 mg of citalopram in order to attempt suicide. In contrast to other
      case reports in adults, our patient showed only mild neurological symptoms and no
      cardiac toxicity or symptoms of a serotonin syndrome, despite a high citalopram
      blood concentration measured about two hours following ingestion of citalopram
      (633 ng/ml; therapeutic reference range for adults 50-110 ng/ml).

PMID- 30185095
TI  - Risk factors for development of early infectious and noninfectious complications
      in systemic lupus erythematosus patients undergoing major surgery.
AB  - Background We aimed to identify risk factors for early complications in systemic
      lupus erythematosus (SLE) patients undergoing major surgery. Methods We conducted
      a retrospective comparative cohort study including patients with SLE undergoing
      major surgery, and non-SLE patients matched 1:1. Main outcomes were development
      of infectious and noninfectious complications, and 30-day postoperative
      mortality. Results A total of 382 patients (191 SLE and 191 non-SLE) were
      included. Postoperative complications occurred in 82 (43%) SLE patients and 58
      (30%) without SLE, ( p = 0.01). Variables associated with infectious
      complications in SLE patients: prednisone use (OR 1.81, 95% CI 1.13-2.90), anemia
      (OR 2.43, 95% CI 1.45-4.08), hypoalbuminemia (OR 2.58, 95% CI 1.55-4.30) and
      lymphopenia (OR 2.43, 95% CI 1.52-3.89), p < 0.05. Variables associated with
      noninfectious complications: anemia (OR, 1.93, 95% CI 1.03-3.64) and
      hypoalbuminemia (OR 2.11, 95% CI 1.16-3.86), p < 0.05. Variables associated with
      any complication: SLEDAI-2K (OR 1.1, 95% CI 1.01-1.20), nephritis (OR 10.08, 95%
      CI 1.21-83.63), aspirin use (OR 2.68, 95% CI 1.19-6.02, p = 0.01), low C3 (OR
      2.00, 95% CI 1.06-3.80), anemia (OR 2.68, 95% CI 1.39-5.18), hypoalbuminemia (OR
      3.49, 95% CI 1.83-6.66) and lymphopenia (OR 2.36, 95% CI 1.30-4.26), p < 0.05.
      More patients with SLE died (6% vs 1%, p = 0.02). Conclusions SLE patients
      present higher frequency of postoperative complications and mortality compared
      with non-SLE patients. Hypoalbuminemia, anemia, lymphopenia and aspirin use are
      independent risk factors.

PMID- 30185096
TI  - Incidence and variables associated with short and long-term mortality in patients
      with systemic lupus erythematosus and sepsis admitted in intensive care units.
AB  - Background Infections are common among patients with systemic lupus erythematosus
      (SLE), and are associated with increased morbidity and mortality. Objectives To
      determine whether SLE is an independent risk factor for short- and long-term
      mortality in patients admitted to an intensive care unit (ICU) with sepsis, and
      to identify the characteristics of SLE patients admitted to an ICU with sepsis.
      Methods A retrospective age- and sex-matched cohort study, based on data of the
      SEPSIS-ISR (Sepsis Israel) Registry, an ongoing study that collects data on all
      patients admitted with sepsis to the ICUs. The primary outcome was to determine
      whether SLE is an independent risk factor for 30-day and 3-year mortality.
      Secondary outcomes were 30-day and 3-year survival rates, and the identification
      of variables associated with mortality within the group of patients with SLE.
      Results In total, 29 SLE and 87 non-SLE patients (median age 55 years; 79.3%
      females) were included. The primary sites of infection as well as pathogen
      distributions were similar between the two groups. The most common infections
      among the SLE and non-SLE patients were pneumonia (48.3 vs. 31%, p = 0.09),
      urinary tract infection (20.7 vs. 14.9%, p = 0.56) and peritonitis (13.8 vs.
      16.1%, p = 0.77). Severe sepsis and septic shock were diagnosed in 79.3 versus
      80.5% ( p = 0.89) and 55.2 versus 33.3% ( p = 0.04) of the SLE and non-SLE
      patients, respectively. The 30-day and 3-year survival rates did not differ
      between SLE and non-SLE patients, and were 69 versus 67.8% ( p = 0.79) and 41.4
      versus 47.1% ( p = 0.69), respectively. In multivariate Cox regression analysis,
      age (hazard ratio (HR) = 1.02; 95% confidence interval (CI) 1.00-1.05) and
      cardiovascular involvement during sepsis (HR = 3.32; 95% CI 1.4-7.86) were
      significant independent risk factors for 30-day mortality. Multiorgan dysfunction
      during sepsis admission was associated with increased 3-year mortality (HR =
      1.37; 95% CI 1.07-1.75). Conclusions SLE is not an independent risk factor for 30
      day or 3-year mortality following ICU admission with sepsis. Increased late
      mortality was associated with congestive heart failure within the SLE patients
      alone. None of the SLE-related variables were statistically different between the
      living and deceased SLE patients.

PMID- 30185097
TI  - Robot-assisted laparoscopic cystectomy with intracorporeal urinary diversion vs.
      open mini-laparotomy cystectomy: evaluation of surgical inflammatory response and
      immunosuppressive ability of CO2-pneumoperitoneum in an experimental porcine
      study.
AB  - OBJECTS: To compare surgical inflammatory response (SIR) after radical cystectomy
      (RC) in a porcine model using minimal invasive techniques. Additionally we aimed
      to investigate the potential immunosuppressive ability of preoperative CO2
      pneumoperitoneum (CO2P). MATERIALS AND METHODS: Forty female landrace pigs were
      randomized to five groups: Three intervention groups all having a cystectomy and
      an ileal conduit either done by robot-assisted laparoscopic technique with
      intracorporeal urinary diversion (RALC) or an open mini-laparotomy with or
      without prior CO2P (OMC +/- CO2P). Two control sham groups with or without prior
      CO2P (S +/- CO2P). Serum samples were obtained preoperatively, immediately
      postoperative, 24, 48 and 72 hours postoperatively, and the inflammatory
      mediators CRP, Haptoglobin, Ceruloplasmin, Albumin, Cortisol, IL-4, IL-6, IL-12
      and IFN-alpha were measured. RESULTS: Operative time was significantly longer in
      RALC compared to open groups (OMC +/- CO2P) (p's < .0001). CRP and Haptoglobin
      levels were significantly higher for surgical intervention groups (SIG) compared
      to controls 24, 48 and 72 hours postoperatively (p's < .001). At 48 hours, CRP
      was higher for RALC vs OMC + CO2P (p = .029). At 72 hours, Haptoglobin was higher
      for RALC vs open groups (p's < .024). Ceruloplasmin, cortisol, albumin, IL-4, IL
      6, IL-12 and IFN-alpha, revealed no significant differences between SIG.
      CONCLUSIONS: No major differences were found between RALC and OMC regarding the
      degree of tissue trauma quantified by inflammatory markers. Thirty minutes of CO2
      insufflation preoperative appears to have a transient immunosuppressive effect of
      the innate postoperative SIR, whereas prolonged CO2P apparently diminishes this
      effect.

PMID- 30185098
TI  - Clinical relevance of reporting fatty liver on ultrasound in asymptomatic
      patients during routine health checkups.
AB  - OBJECTIVE: Ultrasonography is an efficient technique for detecting fatty liver.
      Its sensitivity and specificity in detecting moderate to severe fatty liver are
      comparable to those of histology. Fatty liver is associated with abnormal lipid
      and lipoprotein metabolism and insulin resistance, metabolic syndrome,
      cardiovascular/renal disease, type 2 diabetes, and other conditions. This study
      was performed to compare the serum lipid profiles and serum glutamic pyruvic
      transaminase (GPT), glutamic oxaloacetic transaminase (GOT), and glycosylated
      hemoglobin (HbA1c) levels in patients diagnosed with fatty liver on
      ultrasonography versus controls without fatty liver and evaluate the clinical
      relevance of an ultrasound diagnosis of fatty liver in routine health checkups.
      METHODS: This hospital-based cross-sectional study included 390 patients who
      underwent health checkups; 226 were diagnosed with fatty liver (cases) and 164
      were not (controls). The lipid profile, serum GOT and GPT levels, and HbA1c level
      were compared between the cases and controls. RESULTS: The cases had considerably
      higher levels of lipids, liver enzymes (serum GOT and GPT), and HbA1c than
      controls. CONCLUSION: Ultrasonography is a noninvasive simple tool for early
      detection of fatty liver in asymptomatic patients and can help clinicians achieve
      early detection of metabolic syndrome.

PMID- 30185099
TI  - Providing Social Support to Female Olympic Athletes.
AB  - Support providers may experience positive and negative outcomes associated with
      supporting others. However, there is a lack of research on support provision to
      elite athletes and the views of athletes' support providers. This study addressed
      this gap by exploring the experiences of providing and receiving support between
      female Olympians and their main support providers. Five female Olympians and
      their main support providers participated in separate semistructured interviews.
      It appeared that support provision was personally and professionally rewarding,
      as well as challenging, for support providers, and athletes were generally
      satisfied with the support they received. Athletes appeared highly dependent on
      their support providers, but both athletes and support providers felt that high
      levels of support were necessary for athletic success. Further research is needed
      to understand how support providers are able to foster their own personally
      supportive relationships and whether high levels of interpersonal dependence are
      required to achieve athletic success.

PMID- 30185101
TI  - Underdiagnosis of psychiatric disorders in people with intellectual disabilities:
      Differences between psychiatric disorders and challenging behaviour.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to assess the level of
      mental disorders and challenging behaviour in individuals with intellectual
      disability (ID) supported by specialized services, but without a prior
      psychiatric diagnosis, and to compare the levels of different disorders depending
      on the severity of ID. METHODS: This is a cross-sectional study ( N = 142) of
      population with ID. Inclusion criteria were the following: adult patients with ID
      and with no previous psychiatric diagnosis prior to this survey. The Wechsler
      Adults Intelligence Scale-II, the Psychiatric Assessment Schedule for Adults with
      Developmental Disability checklist and clinical interview, the Diagnostic
      Assessment for the Severely Handicapped scale and the Inventory for Client and
      Agency Planning were the assessment tools. RESULTS: A previously undiagnosed
      mental disorder was found in 29.6% of the sample. The most prevalent mental
      disorders were major depressive and anxiety disorders. An association between
      psychiatric comorbidity and challenging behaviour was found only for
      mild/moderate ID, especially for affective disorders. CONCLUSIONS: The presence
      of a psychiatric as well as a medical comorbidity is associated with severe ID,
      unlike challenging behaviour. Clinical limitations of the study have been
      discussed.

PMID- 30185100
TI  - Arterial blood gas changes during cardiac arrest and cardiopulmonary
      resuscitation combined with passive oxygenation/ventilation: a METI HPS study.
AB  - OBJECTIVE: High-fidelity simulators can simulate physiological responses to
      medical interventions. The dynamics of the partial arterial pressure of oxygen
      (PaO2), partial arterial pressure of carbon dioxide (PaCO2), and oxygen pulse
      saturation (SpO2) during simulated cardiopulmonary resuscitation (CPR) were
      observed and compared with the results from the literature. METHODS: Three
      periods of cardiac arrest were simulated using the METI Human Patient SimulatorTM
      (Medical Education Technologies, Inc., Sarasota, FL, USA): cardiac arrest, chest
      compression-only CPR, and chest compression-only CPR with continuous flow
      insufflation of oxygen (CFIO). RESULTS: In the first period, the observed values
      remained constant. In the second period, PaCO2 started to rise and peaked at 63.5
      mmHg. In the CFIO period, PaCO2 slightly fell. PaO2 and SpO2 declined only in the
      second period, reaching their lowest values of 44 mmHg and 70%, respectively. In
      the CFIO period, PaO2 began to rise and peaked at 614 mmHg. SpO2 exceeded 94%
      after 2 minutes of CFIO. CONCLUSIONS: The METI Human Patient SimulatorTM
      accurately simulated the dynamics of changes in PaCO2. Use of this METI
      oxygenation model has some limitations because the simulated levels of PaO2 and
      SpO2 during cardiac arrest correlate poorly with the results from published
      studies.

PMID- 30185103
TI  - Safety, Reliability, Human Factors, and Human Error in Nuclear Power Plants.

PMID- 30185102
TI  - ST3GAL5-Related Disorders: A Deficiency in Ganglioside Metabolism and a Genetic
      Cause of Intellectual Disability and Choreoathetosis.
AB  - GM3 synthase deficiency is due to biallelic pathogenic variants in ST3GAL5, which
      encodes a sialyltransferase that synthesizes ganglioside GM3. Key features of
      this rare autosomal recessive condition include profound intellectual disability,
      failure to thrive and infantile onset epilepsy. We expand the phenotypic spectrum
      with 3 siblings who were found by whole exome sequencing to have a homozygous
      pathogenic variant in ST3GAL5, and we compare these cases to those previously
      described in the literature. The siblings had normal birth history, subsequent
      developmental stagnation, profound intellectual disability, choreoathetosis,
      failure to thrive, and visual and hearing impairment. Ichthyosis and self
      injurious behavior are newly described in our patients and may influence clinical
      management. We conclude that GM3 synthase deficiency is a neurodevelopmental
      disorder with consistent features of profound intellectual disability,
      choreoathetosis, and deafness. Other phenotypic features have variable
      expressivity, including failure to thrive, epilepsy, regression, vision
      impairment, and skin findings. Our analysis demonstrates a broader phenotypic
      range of this potentially under-recognized disorder.

PMID- 30185104
TI  - A Dual Stimuli Approach Combined with Convolutional Neural Network to Improve
      Information Transfer Rate of Event-Related Potential-Based Brain-Computer
      Interface.
AB  - Increasing command generation rate of an event-related potential-based brain
      robot system is challenging, because of limited information transfer rate of a
      brain-computer interface system. To improve the rate, we propose a dual stimuli
      approach that is flashing a robot image and is scanning another robot image
      simultaneously. Two kinds of event-related potentials, N200 and P300 potentials,
      evoked in this dual stimuli condition are decoded by a convolutional neural
      network. Compared with the traditional approaches, this proposed approach
      significantly improves the online information transfer rate from 23.0 or 17.8 to
      39.1 bits/min at an accuracy of 91.7%. These results suggest that combining
      multiple types of stimuli to evoke distinguishable ERPs might be a promising
      direction to improve the command generation rate in the brain-computer interface.

PMID- 30185105
TI  - A systematic review of obesity interventions targeting anthropometric changes in
      youth with intellectual disabilities.
AB  - Due to the increased prevalence of obesity and disparity experienced by youth
      with intellectual disabilities, efforts to synthesize existing knowledge of
      interventions to attenuate obesity within this marginalized population is
      imperative. The purpose of this investigation is to systematically analyze
      interventions targeting anthropometric changes in youth with intellectual
      disabilities. A search of Cumulative Index of Nursing and Allied Health
      Literature, Educational Resources Information Center, Medical Literature Analysis
      and Retrieval System Online, and Psychological Information Database was conducted
      for the time frame of January 2006 to October 2016. Data extraction resulted in a
      total of 10 interventions that met inclusion criteria. Included studies mainly
      comprised participants having mild-to-moderate intellectual disability with
      diverse comorbidities. Five studies indicated significant positive outcomes in at
      least one anthropometric measure. The majority of programs utilized physical
      activity targeting individual-level change as the primary intervention modality.
      Weaknesses of the reviewed studies and inconclusive evidence indicate the need
      for additional research to gauge the effectiveness of interventions to treat
      obesity among youth with intellectual disabilities.

PMID- 30185106
TI  - Effect of alternative positions of neonates prior to delayed cord clamping on
      placental transfusion: a randomized control trial.
AB  - OBJECTIVE: To determine the effect of alternative positions (relative to
      placenta) of normal term neonates, prior to the recommended delayed cord
      clamping, on placental transfusion and short-term neonatal outcome. METHODS:
      Normal term neonates born vaginally were randomly assigned to be placed either on
      mother's abdomen (Group AL, n = 97) or 20 cm below the introitus (Group BL, n =
      102) for 90 seconds after delivery. Subsequently the cord was clamped. Outcome
      measures were anthropometry, hematological profile including ferritin at birth
      and at 3-4 months; and adverse effects, polycythemia, and jaundice. RESULTS: Both
      groups had comparable outcome measures at birth. At 3-4 months, mean hemoglobin
      (AL: 12.0 +/- 0.9 g/dl, BL: 12.3 +/- 1.1 g/dl; p = .02, 95% CI: 0.03-0.58) and
      hematocrit (AL: 36.1 +/- 2.7%, BL: 37 +/- 3.2%; p = .01, 95% CI: 0.1-1.75) were
      significantly higher in BL group. Anthropometry, serum ferritin, incidence of
      anemia and iron deficiency at 3-4 months were similar in both groups. There was
      no significant difference in polycythemia, jaundice requiring phototherapy or
      respiratory distress between the two groups. CONCLUSIONS: Placing the baby below
      the placenta resulted in a statistically significant increase in hemoglobin and
      hematocrit at 3-4 months without any adverse outcomes. However, this meager
      quantum of increase did not translate into reduction of risk of anemia or
      improvement in iron stores.

PMID- 30185107
TI  - Information design: research and practice.

PMID- 30185108
TI  - Surprise: unfolding of facial expressions.
AB  - Responses to surprising events are dynamic. We argue that initial responses are
      primarily driven by the unexpectedness of the surprising event and reflect an
      interrupted and surprised state in which the outcome does not make sense yet.
      Later responses, after sense-making, are more likely to incorporate the valence
      of the outcome itself. To identify initial and later responses to surprising
      stimuli, we conducted two repetition-change studies and coded the general valence
      of facial expressions using computerised facial coding and specific facial action
      using the Facial Action Coding System (FACS). Results partly supported our
      unfolding logic. The computerised coding showed that initial expressions to
      positive surprises were less positive than later expressions. Moreover,
      expressions to positive and negative surprises were initially similar, but after
      some time differentiated depending on the valence of the event. Importantly,
      these patterns were particularly pronounced in a subset of facially expressive
      participants, who also showed facial action in the FACS coding. The FACS data
      showed that the initial phase was characterised by limited facial action, whereas
      the later increase in positivity seems to be explained by smiling. Conceptual as
      well as methodological implications are discussed.

PMID- 30185110
TI  - Microbial production of neryl-alpha-D-glucopyranoside from nerol by Agrobacterium
      sp. M-12 reflects glucosyl transfer activity.
AB  - Terpene alcohol is widely used in perfumes and is known to possess antibacterial
      activity. Moreover, in its glycosylated form, it can be applied as a nonionic
      surfactant in food, and in the pharmaceutical, chemical, cosmetic, and detergent
      industries. Presently, chemical production of terpene glucosides is hampered by
      high costs and low yields. Here, we investigated the microbial glucosylation of
      nerol (cis-3,7-dimethylocta-2,6-dien-1-ol), a component of volatile oils, by
      Agrobacterium sp. M-12 isolated from soil. A microbial reaction using washed
      cells of Agrobacterium sp. M-12, 1 g/L of nerol, and 100 g/L of maltose under
      optimal conditions yielded 1.8 g/L of neryl-alpha-D-glucopyranoside after 72 h.
      The molar yield of neryl-alpha-D-glucopyranoside was 87.6%. Additionally, we
      report the successful transglucosylation of other monoterpene alcohols, such as
      geraniol, (-)-beta-citronellol, and (-)-linalool, by Agrobacterium sp. M-12.
      Thus, microbial glucosylation has potential widespread applicability for
      efficient, low-cost production of glycosylated terpene alcohols.

PMID- 30185109
TI  - Evaluation of human pineal gland acetylserotonin O-methyltransferase
      immunoreactivity in suicide: A preliminary study.
AB  - Disorders of the serotonergic system are especially known to be present in the
      neurobiology of suicidal behavior. Studies investigating melatonin levels show
      that changes in pineal gland functions may also play a role in the pathogenesis
      of suicide. However, to our knowledge, there are no studies evaluating the
      activity of pinealocytes responsible for melatonin synthesis in suicide. This
      preliminary study aimed to investigate the relationship among pinealocyte,
      acetylserotonin O-methyltransferase (ASMT) immunoreactivity, and suicide. Samples
      of pineal gland, cerebrospinal fluid, blood, and urine were obtained from 21
      suicide and 21 non-suicide cases on which medicolegal autopsies were performed.
      Expression of ASMT in human pineal gland was evaluated by immunohistochemical
      methods. A scoring system was used to define the anti-ASMT-positive staining in
      the sections. Enzyme-linked immunosorbent assays were employed to assess serum
      and cerebrospinal fluid melatonin levels and blood and urine noradrenaline
      levels. The ASMT-immunopositive pinealocyte count was observed to be lower in
      suicide cases compared to the non-suicide cases. With the exception of two cases
      (with moderate staining), all graded scores were 3 (strong staining) in non
      suicide group, whereas scores were 1 (mild staining) or 2 (moderate staining) in
      the suicide group. Melatonin levels in the blood were lower among the suicide
      victims. These results support decreased pineal gland activity in suicide.
      However, further studies are needed to assess whether these changes are related
      to a psychiatric disorder.

PMID- 30185111
TI  - Effect of Blocked Versus Random Practice on Physical Therapy Students' Manual
      Force Modulation.
AB  - This study examined (a) the effect of practice organization on learning to
      modulate manual force, and (b) the effect of force magnitude on ability to
      accurately reproduce force. I randomly assigned 52 novice physical therapy
      students to either blocked or random practice schedules as they learned to apply
      different manual forces. I tested students immediately after training and one
      week later, using a three-way mixed design analysis of variance to assess the
      effects of practice organization (random vs. blocked), test (immediate posttest
      vs. retention test), and force (high vs. low) on ability to modulate manual
      forces. I found that blocked versus random practice, led to more accurate force
      application at the posttest and retention test, F(1, 50) = 5.57, p < .05; both
      practice groups performed more accurately at the posttest than at the retention
      test, F(1, 50) = 5.6, p < .05, and both performed more accurately at the lower,
      compared with the higher, force level, F(1, 50) = 60.9, p < .05. These findings
      support use of a blocked' practice schedule for this motor training, though
      relevant contextual interference moderators may include such variables as nature
      of the task, learners' skill levels, and practice time. In addition, higher
      forces resulted in greater errors and must be considered in preparing for and
      engaging in clinical practice.

PMID- 30185112
TI  - The effects of habituation and adding a rest-frame on experienced simulator
      sickness in an advanced mobility scooter driving simulator.
AB  - The aim of this article is to investigate the effect of a physical rest-frame,
      habituation and age on simulator sickness in an advanced mobility scooter driving
      simulator. Twenty-six young and 34 older adults completed a total of 12 drives in
      an advanced mobility scooter driving simulator over two visits. A 2x2 crossover
      design was used to measure the effect of a rest frame that was added to the
      driving simulator on either the first or second visit. The Simulator Sickness
      Questionnaire was used to measure simulator sickness symptoms. A significant
      decrease in simulator sickness was observed between the first and the second
      visit. Older adults reported more severe simulator sickness symptoms compared to
      younger participants. No effect of rest-frame could be found. Habituation appears
      to be the most effective method to reduce simulator sickness in an advanced
      mobility scooter driving simulator. More research is needed to investigate
      simulator sickness in patient groups. Practitioner summary: Experiencing
      simulator sickness is a major problem across all types of simulators. The present
      experiment investigated the effect of a rest-frame, habituation and age on
      developing simulator sickness symptoms in an advanced mobility scooter driving
      simulator. Habituation appeared to be the most effective method to reduce
      simulator sickness.

PMID- 30185113
TI  - Benzyl isothiocyanate ameliorates lipid accumulation in 3T3-L1 preadipocytes
      during adipocyte differentiation.
AB  - Benzyl isothiocyanate (BITC) is an organosulfur compound derived from cruciferous
      vegetables and papaya seeds. In this study, we investigated the effect of BITC on
      the lipid accumulation in 3T3-L1 preadipocytes during adipocyte differentiation.
      The treatment of BITC during the differentiation-inducing stage significantly
      ameliorated the lipid accumulation, whereas it had no inhibitory effect during
      the differentiation-maintaining stage. BITC also significantly suppressed the
      mRNA expression of the adipocyte-specific markers, such as CCAAT/enhancer-binding
      protein alpha (C/EBPalpha), C/EBPbeta, C/EBPdelta and peroxisome proliferator
      activated receptor gamma. BITC significantly inhibited the phosphorylation of
      extracellular signal-regulated kinase phosphorylation, whereas it enhanced that
      of AMP-activated protein kinase. Furthermore, BITC significantly suppressed the
      intracellular 2-deoxyglucose uptake as well as glucose transporter 4 expression.
      These results suggest that inhibition of the adipocyte differentiation and
      glucose uptake may mainly contribute to the inhibitory effect of BITC on the
      lipid accumulation in 3T3-L1 preadipocytes. Abbreviations: PPARgamma: peroxisome
      proliferator-activated receptor gamma; CEBP: CCAAT/enhancer-binding protein;
      GLUT4: glucose transporter 4; AMPK: AMP-activated protein kinase; ERK1/2:
      extracellular signal-regulated kinase 1/2; MAPK: a mitogen-activated protein
      kinase; ITCs: isothiocyanates; BITC: benzyl isothiocyanate; FBS: fetal bovine
      serum; CS: calf serum; AITC: allyl ITC; IBMX: 3-isobutyl-1-methylxanthine; LDH:
      lactate dehydrogenase; KRH: Krebs-Ringer-Hepes-bicarbonate; 2-DG: 2-deoxy-d
      glucose.

PMID- 30185114
TI  - Navigating the Intangible: Working With Nonphysical Suffering on the Front Lines
      of Palliative Care.
AB  - While relieving suffering is palliative care's primary aim, how palliative care
      providers navigate patients' nonphysical suffering in their day-to-day work and
      the impact of working with nonphysical suffering on the clinician have been
      understudied. This exploratory study aims to begin to fill this gap in the
      literature. Results revealed that palliative care clinicians face several
      challenges in their efforts to navigate patients' nonphysical suffering in their
      day-to-day work, including (a) the intangible nature of nonphysical suffering,
      (b) systemic barriers (e.g., lack of time and adequate resources), (c) clinician
      helplessness or suffering, and (d) a lack of education, training, and support for
      clinicians specific to their work with patients' nonphysical suffering. Study
      outcomes have the potential to improve frontline clinical care with patients and
      support and education for clinicians.

PMID- 30185115
TI  - Corrigendum.

PMID- 30185116
TI  - Modelling distributed crewing in commercial aircraft with STAMP for a rapid
      decompression hazard.
AB  - Changes to crewing configurations in commercial airlines are likely as a means of
      reducing operating costs. To consider the safety implications for a distributed
      crewing configuration, system theoretic accident model and processes (STAMP) was
      applied to a rapid decompression hazard. High level control structures for
      current operations and distributed crewing are presented. The CONOPS generated by
      STAMP-STPA for distributed crewing, and design constraints associated with unsafe
      control actions (UCAs) are offered to progress in the route to certification for
      distributed crewing, and improve safety in current operations. Control loops
      between stakeholders were created using system-theoretic process analysis (STPA).
      The factors leading to the Helios 255 incident demonstrated the redundancy that a
      ground station could offer without the risk of hypoxia, during a decompression
      incident. STPA analysis also highlighted initial UCAs that could occur within the
      hypothetical distributed crewing configuration, prompting consideration of design
      constraints and new CONOPS for ground station design. Practitioner Summary: SPO
      in commercial aircraft is likely as a means to reduce costs. This paper makes a
      case for distributed crewing using STAMP-STPA. Comparing current operations with
      a distributed crewing configuration, the redundancy offered by a ground station
      is demonstrated. Design constraints and new CONOPs for distributed crewing, and
      current operations are proposed.

PMID- 30185118
TI  - Introduction to the Rasch Poisson Counts Model: An R Tutorial.
AB  - The Rasch Poisson Counts Model is the oldest Rasch model developed by the Danish
      mathematician Georg Rasch in 1952. Nevertheless, the model has had limited
      applications in psychoeducational assessment. With the rise of neurocognitive and
      psychomotor testing, there is more room for new applications of the model where
      other item response theory models cannot be applied. In this paper, we give a
      general introduction to the Rasch Poisson Counts Model and then using data of an
      attention test walk the reader through how to use the "lme4" package in R to
      estimate the model and interpret the outputs.

PMID- 30185119
TI  - Recalled Parenting Practices and Psychological Distress in Turkish Emerging
      Adults: The Role of Self-Criticism.
AB  - Research investigating the development of psychological problems among children
      has typically focused on the role of parenting practices. The purpose of this
      study was to investigate the direct effects of recalled parenting practices
      (emotional warmth, rejection, and overprotection) on psychological distress and
      indirect effects through self-criticism. Participants were 410 undergraduate
      students (290 females and 120 males) with a mean age of 20.10 ( SD = 1.65).
      Participants completed the measure of My Memories of Upbringing-Egna Minnen
      Betraffande Uppfostra; Forms of Self Criticizing/Attacking and Self Reassuring
      Scale; and Depression, Anxiety, and Stress Scale as self-report measures. Results
      provided evidence for highly similar patterns of associations among parenting
      practices, self-criticism, and psychological distress for both maternal and
      paternal models. Findings showed that parental emotional warmth and rejection
      were directly related to self-criticism and were indirectly related to
      psychological distress through self-criticism. Only maternal rejection was
      directly related to psychological distress. However, maternal and paternal
      overprotection was not related to psychological distress either directly or
      indirectly. Moreover, maternal and paternal parenting practices explained 61% and
      58% of the variance in psychological distress, respectively. The findings of the
      present study highlighted the importance of self-criticism and past memories of
      parenting as intervention targets to support well-being of young people.

PMID- 30185117
TI  - Extensive intraperitoneal lavage to eliminate intraperitoneal tumor cells in
      gastrectomy with D2 lymphadenectomy for gastric cancer.
AB  - INTRODUCTION:: Survival in gastric cancer is often limited by peritoneal
      carcinomatosis, which supposedly develops from serosal tumor infiltration or
      tumor cell spread during gastrectomy with lymphadenectomy. To eliminate
      peritoneal tumor cells, extensive intraperitoneal lavage (EIPL) has been
      suggested. Impressive results have been achieved in Japanese trials. In this
      trial, we assessed EIPL in Western patients. METHODS:: This prospective trial
      included patients with non-metastatic gastric adenocarcinoma undergoing
      gastrectomy with D2 lymphadenectomy. Peritoneal fluid samples at laparotomy,
      after lymphadenectomy, and after EIPL were analyzed for tumor cells using
      cytology and EpCAM antibodies. The primary endpoint was peritoneal conversion
      rate (PCR; proportion of patients in whom EIPL eliminated tumor cells after
      lymphadenectomy). Secondary endpoints were peritoneal release rate (PRR;
      proportion of patients with peritoneal tumor cells after
      gastrectomy/lymphadenectomy among all patients without cells before
      gastrectomy/lymphadenectomy) and prevalence of peritoneal tumor cells before
      resection. EIPL was considered ineffective if PCR ? 0.2 and warranted further
      exploration if PCR ? 0.5. Clinicaltrials.gov identifier is NCT01476553. RESULTS::
      The trial was stopped early because tumor cells after gastrectomy/lymphadenectomy
      were detected in only 3/27 (11.1%) patients. In none of these did EIPL eliminate
      tumor cells (PCR 0, 95% confidence interval [CI] 0%-12.5%). In 8/27 (29.6%)
      patients, tumor cells were detected after EIPL. PRR was 11.1% (95% CI 2.4%
      29.2%). There were no perioperative complications higher than Clavien-Dindo grade
      3a. CONCLUSIONS:: In Western patients, free peritoneal tumor cells after
      gastrectomy with D2 lymphadenectomy for gastric cancer were detected only
      sporadically. Although based on few cases, the findings suggest that EIPL spreads
      tumor cells into the peritoneal cavity, thus being potentially harmful.
      Therefore, EIPL cannot be generally recommended.

PMID- 30185120
TI  - The Use of Online Pornography as Compensation for Loneliness and Lack of Social
      Ties Among Israeli Adolescents.
AB  - The Internet provides people with the ability to act anonymously, which may lead
      them to feel secure and to release them from many of their inhibitions. In many
      cases, this leads them to participate in cybersex activities and online
      pornography. This study examined the psychological factors behind young people's
      sexual behavior online. Participants comprised 713 Israeli adolescents (383 boys
      and 330 girls) aged 14 to 18 years. Our results indicated that the impact of
      loneliness on online sexual activity and frequency of pornography use was
      dependent on participants' attachment orientations. Engagement in online sexual
      activities and use of pornography were high among anxiously attached individuals
      regardless of the extent of their loneliness. Loneliness was found to increase
      the use of online sexual activities and pornography, only among secure and
      anxiously avoidant individuals. Online sexual activity and pornography were also
      found to be related to offline sexual activity. The results are described and
      discussed.

PMID- 30185121
TI  - Opioids: From Being a Doctor to Being a Patient.

PMID- 30185122
TI  - Sequential Intercept Mapping: Developing Systems-Level Solutions for the Opioid
      Epidemic.
AB  - Sequential intercept mapping, a community-based application of the sequential
      intercept model, was recently adapted in Ohio to address the complex challenge of
      the opioid crisis. Sequential intercept mapping for opioids provides a framework
      for criminal justice, mental health and addictions treatment providers, family
      members and opioid-involved individuals, and other stakeholders to develop
      community-based responses that emphasize prevention, regulation, and treatment
      for opioid dependency, with a goal of reducing unintended deaths and overdoses.
      The authors describe a promising approach to using sequential intercept mapping
      to address the opioid crisis.

PMID- 30185123
TI  - Addressing the Opioid Epidemic in Rural America.

PMID- 30185124
TI  - Important Questions About the Impact of Medical Marijuana on People With Serious
      Mental Illness.
AB  - Many people are interested in using marijuana for therapeutic purposes as
      legalization expands across the country. The impact of marijuana depends upon the
      consumed potency and dose of its major psychoactive components,
      tetrahydrocannabinol and cannabidiol, which have very different psychiatric
      effects. This Open Forum discusses what is known about the impact of these
      marijuana constituents on people with serious mental illnesses, who may
      experience many adverse effects and more easily develop addiction with marijuana
      use. As use of medical marijuana increases, mental health clinicians can help
      prevent or address adverse effects by informing themselves and others about
      marijuana's effects and by coordinating with marijuana prescribers.

PMID- 30185125
TI  - Memory encoding of syntactic information involves domain-general attentional
      resources: Evidence from dual-task studies.
AB  - We investigate the type of attention (domain-general or language-specific) used
      during syntactic processing. We focus on syntactic priming: In this task,
      participants listen to a sentence that describes a picture (prime sentence),
      followed by a picture the participants need to describe (target sentence). We
      measure the proportion of times participants use the syntactic structure they
      heard in the prime sentence to describe the current target sentence as a measure
      of syntactic processing. Participants simultaneously conducted a motion-object
      tracking (MOT) task, a task commonly used to tax domain-general attentional
      resources. We manipulated the number of objects the participant had to track; we
      thus measured participants' ability to process syntax while their attention is
      not taxed, slightly taxed, or overly taxed. Performance in the MOT task was
      significantly worse when conducted as a dual task compared with as a single task.
      We observed an inverted U-shaped curve on priming magnitude when conducting the
      MOT task concurrently with prime sentences (i.e., memory encoding), but no effect
      when conducted with target sentences (i.e., memory retrieval). Our results
      illustrate how, during the encoding of syntactic information, domain-general
      attention differentially affects syntactic processing, whereas during the
      retrieval of syntactic information, domain-general attention does not influence
      syntactic processing.

PMID- 30185126
TI  - Sociodemographic, clinical, and psychological characteristics identify groups of
      Italian cancer patients with high rates of unmet needs.
AB  - PURPOSE: Although an optimal goal remains the routine assessment of unmet needs
      of all patients with cancer, particular attention should be paid to those groups
      of patients with characteristics known to be more frequently associated with
      unmet needs in general or with specific areas of need. This report aims to
      describe the sociodemographic, clinical, and psychological characteristics
      associated with higher unmet needs in Italian cancer patients. METHODS: A total
      of 835 cancer patients from different care settings (ward, day hospital, follow
      up ambulatory, rehabilitation unit, and palliative care) filled out the Needs
      Evaluation Questionnaire (NEQ), the Psychological Distress Inventory, and the
      Sense of Coherence Scale. Association of NEQ scores with the clinical and
      demographic variables were tested using analysis of variance. RESULTS: Higher NEQ
      total score was associated with lower educational level, inpatient care setting,
      radiotherapy treatment, psychological distress, and lower resilience trait sense
      of coherence. Different predictors were identified for different areas of unmet
      needs. Care setting, psychological distress, and resilience trait were the
      strongest indicators of unmet needs in every area: information/communication,
      assistance/care, material needs, relational needs, and psychoemotional support.
      CONCLUSIONS: Clinicians should consider that inpatients with a high distress and
      a low resilience trait sense of coherence represent a group of cancer patients to
      be investigated with particular attention regarding unmet needs.

PMID- 30185127
TI  - Marginal iron deficiency enhances liver triglyceride accumulation in rats fed a
      high-sucrose diet.
AB  - We investigated whether marginal iron-deficiency (MID) without anemia influences
      liver lipid accumulation in rats. Ingestion of a MID diet in which the iron
      concentration was half of AIN-93 formulation (iron-adequate, IA) for 3 weeks
      decreased liver iron concentration without anemia. We then evaluated the
      influence of the MID diet on liver lipid accumulation in combination with a high
      sucrose (HS) diet and confirmed that the HS-MID diet successfully decreased liver
      iron concentration without anemia. Additionally, a significant increase in liver
      triglyceride concentration was found, accompanied by upregulation of hepatic
      fatty acid synthase expression in the rats fed the HS-MID diet compared to those
      in the rats fed an HS-IA diet, although no difference was observed in plasma
      transaminase activity and hepatic interleukin-1beta expression. These results
      suggest that MID enhances de novo lipid synthesis via upregulation of lipogenic
      gene expression in combination with sucrose in the diet. Abbreviations: ALT,
      alanine aminotransferase; AST, aspartate aminotransferase; HS, high sucrose; IA,
      iron adequate; ID, iron deficiency; MID, marginal irondeficiency; NAFLD, non
      alcoholic fatty liver disease.

PMID- 30185128
TI  - Cytotoxicity analysis of staphylococcal bi-component beta-pore forming toxins
      using the CHO cells expressing human lymphocyte receptor CCR5.
AB  - CCR5-mediated cytotoxicity of staphylococcal bi-component toxins was investigated
      using human CCR5-expressing CHO cells. Cytotoxicity of rim domain loop-exchange
      mutants between LukE and Hlg2 indicated that loop-4 of LukE is essential for
      cytotoxicity in combination with LukD. Interestingly, Hlg2 showed LukF-dependent
      CCR5-mediated cytotoxicity, suggesting that the F-components of toxins also play
      a role in the cell-specific cytotoxicity.

PMID- 30185129
TI  - Citrus peel polymethoxyflavones, sudachitin and nobiletin, induce distinct
      cellular responses in human keratinocyte HaCaT cells.
AB  - A variety of polyphenols have been isolated from plants, and their biological
      activities have been examined. Sudachitin (5,7,4'-trihydroxy-6,8,3'
      trimethoxyflavone) is a polymethoxyflavone that is isolated from the peel of
      Citrus sudachi. Although we previously reported that sudachitin possesses an anti
      inflammatory activity, its other biological activities are not yet understood. In
      this study, we report a novel biological activity of sudachitin, which
      selectively induced apoptosis in human keratinocyte HaCaT cells. Another
      polymethoxyflavone, nobiletin (5,6,7,8,3',4'-hexamethoxyflavone), promoted
      autophagy but not apoptosis in HaCaT cells. On the other hand, 3'
      demethoxysudachitin (5,7,4'-trihydroxy-6,8-dimethoxyflavone) failed to induce
      apoptosis and autophagy. These results show that three polymethoxyflavones have
      different effects on apoptosis and autophagy in HaCaT cells. Understanding the
      structure and biological activity of polymethoxyflavones may lead to the
      discovery of potential candidates for cancer drug development without significant
      toxic side effects. Abbreviations: ROS: reactive oxygen species; DMSO: dimethyl
      sulfoxide; MTT: 3-(4, 5-dimethylthiazol-2yl)-2, 5-diphenyltetrazolium bromide;
      GAPDH: glyceraldehyde-3-phosphate dehydrogenase; PARP: poly(ADP-ribose)
      polymerase; PI: propidium iodide; MAPK: mitogen-activated protein kinase.

PMID- 30185131
TI  - Thiotepa-induced cutaneous toxicity in pediatric patients: Case report and
      implementation of preventive care guidelines.
AB  - Thiotepa, a highly lipophilic, alkylating agent, and/or its active metabolites
      may be excreted in part via skin in patients receiving high-dose therapy. We
      present a case of cutaneous toxicity observed in a 4.5-year-old girl patient with
      medulloblastoma treated with a high-dose thiotepa conditioning regimen before
      autologous stem cell transplantation. Skin lesions, as well as their pattern and
      locations, were evocative of thiotepa toxidermia. After the case herein
      described, preventive care guidelines were implemented in our unit as from 2014.
      A retrospective follow-up of 26 pediatric patients receiving thiotepa prior to
      stem cell transplantation was performed until March 2018. In this series of
      patients, only one patient experienced cutaneous toxicity as reported herein.
      Thereafter, only mild cutaneous toxicity was observed, even with double or triple
      transplantation protocols with high-dose thiotepa. Clear preventive care
      instructions should be detailed in the Summary of Product Characteristics in
      order to minimize the cutaneous toxicity of thiotepa.

PMID- 30185132
TI  - Development and validation of Nurses' Moral Courage Scale.
AB  - BACKGROUND: Moral courage is required at all levels of nursing. However, there is
      a need for development of instruments to measure nurses' moral courage.
      OBJECTIVES: The objective of this study is to develop a scale to measure nurses'
      self-assessed moral courage, to evaluate the scale's psychometric properties, and
      to briefly describe the current level of nurses' self-assessed moral courage and
      associated socio-demographic factors. RESEARCH DESIGN: In this methodological
      study, non-experimental, cross-sectional exploratory design was applied. The data
      were collected using Nurses' Moral Courage Scale and analysed statistically.
      Participants and research context: The data were collected from a convenience
      sample of 482 nurses from four different clinical fields in a major university
      hospital in Finland for the final testing of the scale. The pilot comprised a
      convenience sample of 129 nurses. Ethical considerations: The study followed good
      scientific inquiry guidelines. Ethical approval was obtained from the university
      ethics committee and permission to conduct the study from the participating
      hospital. FINDINGS: Psychometric evaluation showed that the 4-sub-scale, 21-item
      Nurses' Moral Courage Scale demonstrates good reliability and validity at its
      current state of development showing a good level of internal consistency for a
      new scale, the internal consistency values ranging from 0.73 to 0.82 for sub
      scales and 0.93 for the total scale, thus well exceeding the recommended
      Cronbach's alpha value of >0.7. Principal component analysis and confirmatory
      factor analysis supported the theoretical construct of Nurses' Moral Courage
      Scale. Face validity and expert panel assessments markedly contributed to the
      relevance of items in establishing content validity. DISCUSSION AND CONCLUSION:
      Nurses' Moral Courage Scale provides a new generic instrument intended for
      measuring nurses' self-assessed moral courage. Recognizing the importance of
      moral courage as a part of nurses' moral competence and its assessment offers
      possibilities to develop interventions and educational programs for enhancement
      of moral courage. Research should focus on further validation measures of Nurses'
      Moral Courage Scale in international contexts.

PMID- 30185133
TI  - Novel immunotherapy strategies for hepatobiliary cancers.
AB  - Despite recent advancements in therapeutic options for advanced hepatobiliary
      cancers, there remains an unmet need for innovative systemic treatments.
      Immunotherapy has shown an ability to provide prolonged clinical benefit, but
      this benefit remains limited to a small subset of patients. Numerous ongoing
      endeavors are investigating novel immunotherapy concepts. Immunotherapies that
      have demonstrated clinical efficacy in hepatobiliary cancers include PD-1
      inhibitor therapy and CTLA-4 inhibitor therapy. Novel immunotherapy concepts
      include targeting emerging checkpoint proteins, bispecific T-cell engagers,
      combinatorial trials with checkpoint inhibitors, oncolytic virotherapy and
      chimeric antigen receptor T cells. The goal for these new treatment strategies is
      to achieve a meaningful expansion of patients deriving prolonged clinical benefit
      from immunotherapy.

PMID- 30185134
TI  - Early immune response regulated by a bone marrow mesenchymal stem cell model of
      multiple trauma in rats.
AB  - AIM: To explore whether transplantation of bone marrow mesenchymal stem cells
      (BMSCs) would reduce the immune response and protect vital organs in a rat model
      of femur shaft fracture combined with craniocerebral injury. METHODS: The rats
      were divided into an experimental group (multiple traumas and receiving BMSCs
      injection, n = 25), a positive control group (only received the combination
      injuries, n = 25) and a negative group (n = 5). RESULTS: Compared with the
      positive control group, plasma IL-6 and IL-8 were significantly lower at the
      early stage, and IL-10 was higher at the late period in the experimental group (p
      < 0.05). TNF-alpha ex-vivo synthesis descended quickly after trauma. CONCLUSION:
      BMSCs reduced the inflammatory response and were effective in immunomodulations
      during severe trauma.

PMID- 30185135
TI  - Bone tumors developed in patients with juvenile inflammatory arthritis after anti
      TNFalpha therapy.
AB  - Administration of anti-TNFalpha agents has become a mainstay in the treatment of
      chronic inflammatory arthritis such as rheumatoid arthritis (RA) and
      spondyloarthritis. Adverse events, including infections and allergic reactions,
      have been reported. Malignancies are rare but potentially life threatening. The
      existence of bone tumor in those patients is very rare, only five cases of bone
      tumors were mentioned in juvenile idiopathic arthritis (JIA) in the literature.
      We describe three patients in whom bone neoplasms developed after years of anti
      TNFalpha therapy for JIA or juvenile ankylosing spondylitis (JAS). One patient
      developed chondroblastoma, and the other two were diagnosed with osteosarcoma.
      Rheumatologists should increase their awareness of bone neoplasia in JIA or
      juvenile ankylosing spondylitis patients after anti-TNFalpha treatment.

PMID- 30185136
TI  - The potential immune-eliciting cancer testis antigens in colorectal cancer.
AB  - The identification of cancer testis antigens (CTAs) has been an important finding
      in the search of potential targets for cancer immunotherapy. CTA is one of the
      subfamilies of the large tumor-associated antigens groups. It is aberrantly
      expressed in various types of human tumors but is absent in normal tissues except
      for the testis and placenta. This CTAs-restricted pattern of expression in human
      malignancies together with its potential immunogenic properties, has stirred the
      interest of many researchers to use CTAs as one of the ideal targets in cancer
      immunotherapy. To date, multiple studies have shown that CTAs-based vaccines can
      elicit clinical and immunological responses in different tumors, including
      colorectal cancer (CRC). This review details our current understanding of CTAs
      and CRC in regard to the expression and immunological responses as well as some
      of the critical hurdles in CTAs-based immunotherapy.

PMID- 30185137
TI  - The immune profile of EGFR-mutated non-small-cell lung cancer at disease onset
      and progression after tyrosine kinase inhibitors therapy.

PMID- 30185139
TI  - Rituximab treatment for immune-complex-mediated membranoproliferative
      glomerulonephritis.
AB  - Immune-complex-mediated membranoproliferative glomerulonephritis (MPGN) is a new
      concept that refers to MPGN with immunoglobulin and C3 deposition in the kidney
      based on immunofluorescence examination. It is associated with pathological
      autoantibodies production. Rituximab, as an immunosuppressive agent, can
      eliminate B cells selectively. We reported a case that a patient with immune
      complex-mediated MPGN and HCV infection, but no cryoglobulinemia, responded well
      to the treatment of low-dosage of rituximab and steroids. His proteinuria
      decreased remarkably with the serum creatinine and liver function remaining
      stable within 1 year. His favorable outcome suggests that low-dosage of rituximab
      in conjunction with steroids is an effective and safe treatment choice for immune
      complex-mediated MPGN.

PMID- 30185138
TI  - The current state of immune checkpoint inhibitors in the first-line treatment of
      renal cancer.
AB  - Until recently, tyrosine kinase inhibitors (TKI) were the only approved drugs for
      the first-line treatment of metastatic renal cell carcinoma (mRCC). Emerging
      trials of immune checkpoint inhibitors (ICI)-based regimens have shown survival
      benefits over the standard TKI. These studies challenge a paradigm shift in the
      management of mRCC concerning the identification of the subgroup of patients that
      would benefit from ICI in treatment-naive mRCC, the possibility of treatment
      discontinuation between TKI and ICI, and the sequencing of surgery and systemic
      treatment. This paper reviews the currently available data and discusses the
      paradigm shift concerning first-line treatments of mRCC.

PMID- 30185140
TI  - Monitoring immunotherapy outcomes with circulating tumor DNA.

PMID- 30185141
TI  - Evitar (l-Alanyl-l-Glutamine) Regulates Key Signaling Molecules in the
      Pathogenesis of Postoperative Tissue Fibrosis.
AB  - AIMS: Hypoxia and the resulting oxidative stress play a major role in
      postoperative tissue fibrosis. The objective of this study was to determine the
      effect of l-alanyl-l-glutamine (Ala-Gln) on key markers of postoperative tissue
      fibrosis: hypoxia-inducible factor (HIF) 1alpha and type I collagen. METHODS:
      Primary cultures of human normal peritoneal fibroblasts (NPF) established from
      normal peritoneal tissue were treated with increasing doses of Ala-Gln (0, 1, 2,
      or 10 mM) with hypoxia ([2% O2] 0-48 hours; continuous hypoxia) or after hypoxia
      (0.5, 1, 2, 4 hours) and restoration of normoxia (episodic hypoxia) with
      immediate treatment with Ala-Gln. Hypoxia-inducible factor 1alpha and type 1
      collagen levels were determined by enzyme-linked immunosorbent assay. Data were
      analyzed with 1-way analysis of variance followed by Tukey tests with Bonferroni
      correction. RESULTS: Hypoxia-inducible factor 1alpha and type I collagen levels
      increased in untreated controls by 3- to 4-fold in response to continuous and
      episodic hypoxia in human NPF. Under continuous hypoxia, HIF-1alpha and type I
      collagen levels were suppressed by Ala-Gln in a dose-dependent manner. l-alanyl-l
      glutamine treatment after episodic hypoxia also suppressed HIF-1alpha and type I
      collagen levels for up to 24 hours for all doses and up to 48 hours at the
      highest dose, regardless of exposure time to hypoxia. CONCLUSIONS: l-alanyl-l
      glutamine significantly suppressed hypoxia-induced levels of key tissue fibrosis
      (adhesion) phenotype markers under conditions of continuous as well as episodic
      hypoxia in vitro. This effect of glutamine on molecular events involved in the
      cellular response to insult or injury suggests potential therapeutic value for
      glutamine in the prevention of postoperative tissue fibrosis.

PMID- 30185142
TI  - Diffusion of Handwashing Knowledge and Water Treatment Practices From Mothers in
      an Antenatal Hygiene Promotion Program to Nonpregnant Friends and Relatives,
      Machinga District, Malawi.
AB  - Access to safe drinking water and improved hygiene are essential for preventing
      diarrheal diseases in low- and middle-income countries. Integrating water
      treatment and hygiene products into antenatal clinic care can motivate water
      treatment and handwashing among pregnant women. Free water hygiene kits (water
      storage containers, sodium hypochlorite water treatment solution, and soap) and
      refills of water treatment solution and soap were integrated into antenatal care
      and delivery services in Machinga District, Malawi, resulting in improved water
      treatment and hygiene practices in the home and increased maternal health service
      use. To determine whether water treatment and hygiene practices diffused from
      maternal health program participants to friends and relatives households in the
      same communities, we assessed the practices of 106 nonpregnant friends and
      relatives of these new mothers at baseline and 1-year follow-up. At follow-up,
      friends and relatives were more likely than at baseline to have water treatment
      products observable in the home (33.3% vs. 1.2%, p < 0.00001) and detectable free
      chlorine residual in their water, confirming water treatment (35.7% vs. 1.4%; p <
      0.00001). Qualitative data from in-depth interviews also suggested that program
      participants helped motivate adoption of water treatment and hygiene behaviors
      among their friends and relatives.

PMID- 30185143
TI  - The association between depressive symptoms and fall accidents among middle-aged
      and elderly people in China.
AB  - BACKGROUND: Depressive symptoms are a worldwide health problem. However, the
      research about the effect of depressive symptoms on the fall among the Chinese
      mid-aged and elderly people is lacking. Therefore, this study aims to investigate
      the association between depressive symptoms and fall accidents among middle-aged
      and elderly people in China. METHODS: This study was conducted based on 12,527
      sets of data from China Health and Retirement Longitudinal Survey (CHARLS). The
      2011 depressive symptoms data and the 2013 fall data were chosen for this study.
      The depressive symptom-related data was assessed by the Chinese version of Center
      for Epidemiologic Studies Depression scales (CES-D). Individuals were divided
      into subgroups according to gender (male or female), age (45-59, middle-aged or
      >= 60, elderly people), and residence (rural or urban). The odds ratios (ORs)
      were compared between subgroups using multivariable logistic regression analysis
      method. RESULTS: The adjusted OR value (OR = 1.19 [95% CI 1.07-1.33]) shows there
      is a significant association between depressive symptoms and subsequent fall
      accidents. The ORs of the female, elderly people, rural, and urban subgroups are
      1.31 (95% CI 1.11-1.55), 1.24 (95% CI 1.08-1.43), 1.17 (95% CI 1.02-1.33), and
      1.25 (95% CI 1.04-1.49), respectively, which reveals that this association is
      also statistically significant in these subgroups. CONCLUSIONS: This study shows
      that there is a significant association between depressive symptoms and their
      subsequent fall accidents among the Chinese middle-aged and elderly people.

PMID- 30185145
TI  - Serum progesterone distribution in normal pregnancies compared to pregnancies
      complicated by threatened miscarriage from 5 to 13 weeks gestation: a prospective
      cohort study.
AB  - BACKGROUND: Progesterone is a critical hormone in early pregnancy. A low level of
      serum progesterone is associated with threatened miscarriage. We aim to establish
      the distribution of maternal serum progesterone in normal pregnancies compared to
      pregnancies complicated by threatened miscarriage from 5 to 13 weeks gestation.
      METHODS: This is a single centre, prospective cohort study of 929 patients. Women
      from the Normal Pregnancy [NP] cohort were recruited from antenatal clinics, and
      those in the Threatened Miscarriage [TM] cohort were recruited from emergency
      walk-in clinics. Women with multiple gestations, missed, incomplete or inevitable
      miscarriage were excluded from the study. Quantile regression was used to
      characterize serum progesterone levels in the NP and TM cohorts by estimating the
      10th, 50th and 90th percentiles from 5 to 13 weeks gestation. Pregnancy outcome
      was determined at 16 weeks of gestation. Subgroup analysis within the TM group
      compared progesterone levels of women who subsequently miscarried with those who
      had ongoing pregnancies at 16 weeks of gestation. RESULTS: Median serum
      progesterone concentration demonstrated a linearly increasing trend from 57.5
      nmol/L to 80.8 nmol/L from 5 to 13 weeks gestation in the NP cohort. In the TM
      cohort, median serum progesterone concentration increased from 41.7 nmol/L to
      78.1 nmol/L. However, median progesterone levels were uniformly lower in the TM
      cohort by approximately 10 nmol/L at every gestation week. In the subgroup
      analysis, median serum progesterone concentration in women with ongoing pregnancy
      at 16 weeks gestation demonstrated a linearly increasing trend from 5 to 13 weeks
      gestation. There was a marginal and non-significant increase in serum
      progesterone from 19.0 to 30.3 nmol/L from 5 to 13 weeks gestation in women who
      eventually had a spontaneous miscarriage. CONCLUSIONS: Serum progesterone
      concentration increased linearly with gestational age from 5 to 13 weeks in women
      with normal pregnancies. Women with spontaneous miscarriage showed a marginal and
      non-significant increase in serum progesterone. This study highlights the pivotal
      role of progesterone in supporting an early pregnancy, with lower serum
      progesterone associated with threatened miscarriage and a subsequent complete
      miscarriage at 16 weeks gestation.

PMID- 30185144
TI  - Increased insulin-like growth factor 1 production by polyploid adipose stem cells
      promotes growth of breast cancer cells.
AB  - BACKGROUND: Adipose-tissue stem cells (ASCs) are subject of intensive research
      since their successful use in regenerative therapy. The drawback of ASCs is that
      they may serve as stroma for cancer cells and assist tumor progression. It is
      disquieting that ASCs frequently undergo genetic and epigenetic changes during
      their in vitro propagation. In this study, we describe the polyploidization of
      murine ASCs and the accompanying phenotypical, gene expressional and functional
      changes under long term culturing. METHODS: ASCs were isolated from visceral fat
      of C57BL/6 J mice, and cultured in vitro for prolonged time. The phenotypical
      changes were followed by microscopy and flow cytometry. Gene expressional changes
      were determined by differential transcriptome analysis and changes in protein
      expression were shown by Western blotting. The tumor growth promoting effect of
      ASCs was examined by co-culturing them with 4 T1 murine breast cancer cells.
      RESULTS: After five passages, the proliferation of ASCs decreases and cells enter
      a senescence-like state, from which a proportion of cells escape by
      polyploidization. The resulting ASC line is susceptible to adipogenic, osteogenic
      and chondrogenic differentiation, and expresses the stem cell markers CD29 and
      Sca-1 on an upregulated level. Differential transcriptome analysis of ASCs with
      normal and polyploid karyotype shows altered expression of genes that are
      involved in regulation of cancer, cellular growth and proliferation. We verified
      the increased expression of Klf4 and loss of Nestin on protein level. We found
      that elevated production of insulin-like growth factor 1 by polyploid ASCs
      rendered them more potent in tumor growth promotion in vitro. CONCLUSIONS: Our
      model indicates how ASCs with altered genetic background may support tumor
      progression.

PMID- 30185146
TI  - Comparison of upper airway patency in patients with mild obstructive sleep apnea
      during dexmedetomidine or propofol sedation: a prospective, randomized,
      controlled trial.
AB  - BACKGROUND: In addition to propofol, dexmedetomidine is a suitable alternative
      for intraoperative sedation in procedures requiring regional anesthesia. To date,
      however, little is known about the influences of each drug on upper airway
      patency. Accordingly, the authors investigated differences between
      dexmedetomidine and propofol sedation in the occurrence of upper airway
      obstruction and requirements for airway intervention in patients with mild
      obstructive sleep apnea. METHODS: Patients with an apnea/hypopnea index of 5-14/h
      according to Watch-PAT 200 analysis were enrolled in this study. Spinal
      anesthesia was routinely performed for surgery. Intraoperative sedation was
      initiated using either dexmedetomidine or propofol infusion at a level of
      modified observer's assessment of alertness/sedation scale 3. The primary outcome
      was the proportion of patients exhibiting signs of upper airway obstruction. A
      sign of upper airway obstruction was defined as no detection of end-tidal carbon
      dioxide for at least 10 s despite respiratory efforts. RESULTS: A total of 50
      patients were included in the final analysis (dexmedetomidine [n = 26]; propofol
      [n = 24]). During the intraoperative sedation period, there was a significantly
      lower proportion of patients exhibiting signs of upper airway obstruction in the
      dexmedetomidine group than in the propofol group (11.5% vs. 41.7%, P = 0.035). An
      artificial airway was inserted in 1 patients (3.8%) and 5 patient (20.8%) in the
      dexmedetomidine and propofol groups, respectively (P = 0.093). CONCLUSION:
      Dexmedetomidine sedation was associated with a lower incidence of upper airway
      obstruction than propofol sedation in patients with mild obstructive sleep apnea.
      TRIAL REGISTRATION NUMBER: Clinical trials.gov ( NCT02993718 ): Retrospectively
      registered.

PMID- 30185147
TI  - Leptin: role over central nervous system in epilepsy.
AB  - Adipose tissue is a dynamic organ with different effects on the body. Many of
      these effects are mediated by leptin, a hormone strongly involved in regulation
      of feeding and energy metabolism. It has an important role as a mediator of
      neuronal excitatory activity and higher brain functions. The aim of this study
      was to review the association between leptin and cerebral neuronal function, in
      particular its anticonvulsant or convulsant effects and the possible therapeutic
      role for treating epilepsy. For this purpose, the databases Pubmed, Science
      Direct, Elsevier, ResearchGate and Scielo were searched to identify experimental
      studies, reviews and systematic review articles, published in English, Spanish or
      Portuguese. Experimental studies and the presence of leptin receptors in nervous
      system sites other than the hypothalamus suggest an influence on higher brain
      functions. Indeed several animal studies have demonstrated a role of these
      channels in epileptiform activity as both anticonvulsive and convulsive effects
      have been found. The reason for these discrepancies is unclear but provides clear
      evidence of a potential role of leptin and leptin therapy in epileptiform
      activity. The association between leptin and brain function demonstrates the
      importance of peripheral metabolic hormones on central nervous system and opens a
      new way for the development of novel therapeutic interventions in diseases like
      epilepsy. Nevertheless further investigations are important to clarify the
      dynamics and diverse actions of leptin on excitatory regulation in the brain.

PMID- 30185148
TI  - Procalcitonin kinetics after burn injury and burn surgery in septic and non
      septic patients - a retrospective observational study.
AB  - BACKGROUND: Early sepsis diagnosis is crucial for the correct management of burn
      patients, and it clearly influences outcomes. The systemic inflammatory response
      triggered by burns mimics sepsis presentation and complicates early sepsis
      diagnosis. Biomarkers were advocated to aid the diagnosis of early sepsis. Serum
      procalcitonin (PCT) exhibits fair accuracy and good correlation with sepsis
      severity, being used in diverse clinical settings. However, few studies have
      evaluated perioperative changes in PCT levels in burn patients. The present study
      evaluated PCT kinetics during the first days after burn injury and subsequent
      surgical interventions to assess PCT utility in distinguishing septic from non
      septic inflammatory responses. METHODS: This study was a retrospective
      observational study of all burn patients admitted to the Coimbra Burns Unit
      (Portugal) between January 2011 and December 2014 who presented with a total burn
      surface area >= 15% and who underwent subsequent surgery. PCT kinetics were
      investigated a) during the first five days after burn injury and b)
      preoperatively during the five days after surgery in three subsets of patients,
      including those with no preoperative and no postoperative sepsis (NN), no
      preoperative but postoperative sepsis (NS), and preoperative and postoperative
      sepsis (SS). A total of 145 patients met the selection criteria and were included
      in the analysis. RESULTS: PCT levels in the first five days after burn injury
      were significantly higher in patients who developed at least one sepsis episode
      (n = 85) compared with patients who did not develop sepsis (n = 60). PCT values >
      1.00 ng/mL were clearly associated with sepsis. Study participants (n = 145)
      underwent a total of 283 surgical interventions. Their distribution by
      preoperative/postoperative sepsis status was 142 (50.2%) in NN; 62 (21.9%) in NS;
      and 79 (27.9%) in SS. PCT values exhibited a parallel course in the three groups
      that peaked on the second postoperative day and returned to preoperative levels
      on the third day or later. The lowest PCT values were found in NN, and the
      highest values were observed in SS; the NS values were intermediate. CONCLUSIONS:
      PCT kinetics coupled with a clinical examination may be helpful for sepsis
      diagnosis during the first days after burn injury and burn surgery.

PMID- 30185149
TI  - Factor XIII polymorphism and risk of aneurysmal subarachnoid haemorrhage in a
      south Indian population.
AB  - BACKGROUND: The rupture of a brain aneurysm causes bleeding in the subarachnoid
      space and is known as aneurysmal subarachnoid haemorrhage (aSAH). In our study,
      we evaluated the association of factor XIII polymorphism and the risk of
      Aneurysmal subarachnoid haemorrhage (aSAH) in South Indian population. METHODS:
      The study was performed in 200 subjects with aSAH and 205 healthy control
      subjects. Genotyping of rs5985(c.103G > T (p.Val35Leu)) and rs5982(c.1694C > T
      (p.Pro564Leu)) polymorphism was performed by Taqman(r) allelic discrimination
      assay. RESULTS: In our study, Val/Leu genotype frequency was higher in control
      subjects (18%) compared to aSAH patients (9%).The Val/Leu genotype was associated
      with lower risk of aSAH (OR = 0.48, 95%CI = 0.26-0.88, p = 0.02). When compared
      with Val allele, Leu allele was significantly associated with lower risk of aSAH
      (OR = 0.55, 95%CI = 0.32-0.95, p = 0.03). In subtyping, we found a significant
      association of Leu/Leu genotype with the Basilar top aneurysm (OR = 3.59, 95%CI =
      1.11-11.64, p = 0.03). In c.1694C > T (p.Pro565Leu) variant, Pro/Pro Vs Pro/Leu
      genotype (OR = 2.06, 95%CI = 1.10-3.85, p = 0.02) was significantly associated
      with higher risk of aSAH. The 564Leu allelic frequency in aSAH patients (36%) was
      higher when compared with that in healthy controls (30%) in our study. When
      allele frequency (Pro Vs Leu) was compared, 564Leu allele was found to be
      significantly associated with higher aSAH risk (OR = 1.36, 95%CI = 1.01-1.83, p =
      0.04). (OR = 1.36, 95%CI = 1.01-1.83, p = 0.04). Regarding rs5985 and rs5982,
      significant association was found in the log-additive model (OR = 0.57, 95%CI =
      0.33-0.97, p = 0.034; OR = 1.32, 95%CI = 1.00-1.72, p = 0.043). CONCLUSION: These
      results suggest that 34Leu allele was a protective factor for lower risk of aSAH
      whereas 564Leu allele was associated with higher risk of aSAH in South Indian
      population.

PMID- 30185150
TI  - Successful treatment of endogenous endophthalmitis with extensive subretinal
      abscess: a case report.
AB  - BACKGROUND: Endogenous endophthalmitis could lead to a devastating outcome
      without a prompt and appropriate management. We report a case of advanced
      endogenous Klebsiella pneumoniae endophthalmitis with extensive subretinal
      abscess that was successfully treated with a vitrectomy. CASE PRESENTATION: A
      systemically well 61-year-old man complained of ocular pain and visual decrease
      in his right eye for eighteen days. Ophthalmic examination showed dense
      inflammation in the anterior chamber and vitreous body. Systemic investigations
      discovered diabetes and no specific site of systemic infection was found after
      hospitalization. The inflammation continued to worsen after the intravitreal
      antibiotic injection. Therefore, a pars plana vitrectomy combined with
      phacoemulsification was performed. Intraoperatively, a white elevated, fluffy
      mass with the overlying retinal whitening and necrosis was revealed in superior
      periphery. In addition to this, extensive retinal hemorrhages and five adjacent
      subretinal whitish masses with exudative retinal detachment were observed in the
      posterior pole and inferior quadrants, which were suggestive of extensive
      subretinal abscess with intense overlying retinal inflammation. The excision of
      white fluffy mass superiorly was performed without retinotomy and aspiration of
      extensive subretinal abscess. The polymerase chain reaction of vitreous samples
      was positive for Klebsiella pneumonia. Intravitreal 2 mg/0.1 ml ceftazidime were
      repeated. Nine days after the surgery, the inflammation significantly subsided
      and the retina reattached. The patient was in a stable condition at subsequent
      visit eight months later. CONCLUSION: The delay in an accurate diagnosis and
      treatment caused extensive subretinal abscess combined with endogenous
      endophthalmitis. The treatment modality of subretinal abscess is typically
      individualized to the patient's presentation. If the retina overlying the abscess
      is not necrotic, the extensive subretinal abscess can quickly absorbed after
      vitrectomy, retinotomy with aspiration of the abscess should be avoided to
      decrease the risk of retinal detachment.

PMID- 30185151
TI  - Fine needle aspirates of kidneys: a promising tool for RNA sequencing in native
      and transplanted kidneys.
AB  - BACKGROUND: Transcriptome analysis is emerging as emerging as a promising tool to
      enhance precision of diagnosis and monitoring in solid organ transplantation.
      Clinical progress has however been hampered by the current reliance on samples
      from core needle biopsies. This proof-of-principle study examined whether fine
      needle aspirates, being less invasive, permit the ascertainment of the identical
      molecular information as core biopsies. METHODS: We collected fine needles
      aspirates from various needle sizes (G19, 21, 23, 25) and the corresponding core
      biopsies (G16 needle) of non-tumor tissue of full nephrectomy specimens from
      patients suffering from clear cell renal cell carcinoma (n = 11). RNA expression
      patterns of two gene sets (156 genes) were executed using targeted RNA sequencing
      in samples from fine needle vs. core needle samples. A subgroup of kidneys (n =
      6) also underwent whole transcriptome RNA sequencing from core biopsies of tumor
      and peri-tumoral normal tissue (Tru Seq RNA Access, Illumina). RESULTS: Samples
      from all needle sizes except two G25 aspirates yielded RNA potentially suitable
      for sequencing of both gene sets. The mRNA expression patterns of the two gene
      sets were highly correlated between fine needle aspirates (G23) and corresponding
      (G16) core biopsies (r = 0.985 and 0.982, respectively). This close correlation
      was further documented by heat map, Principal Component Analyses (PCA) and whole
      transcription RNA sequencing. The similarity between fine neddle aspirates and
      core needle biopsies was additionally confirmed in the subgroup with complete RNA
      sequencing. CONCLUSIONS: Fine needle biopsies yield similar genomic information
      to core needle biopsies. The less invasive nature of fine needle biopsies may
      therefore permit more frequent molecular monitoring and a more targeted use of
      core needle biopsies in native and especially in transplanted kidneys.

PMID- 30185152
TI  - Decompression retinopathy following nonpenetrating deep sclerectomy for primary
      congenital glaucoma.
AB  - BACKGROUND: To describe a unique case of decompression retinopathy manifesting as
      pre-macular subhyaloid hemorrhage that occurs in a nine-day old child after
      undergoing a non-penetrating deep sclerectomy for primary congenital glaucoma.
      CASE PRESENTATION: We report a single case of a 9-day-old boy who was referred to
      our department of ophthalmology for bilateral buphtalmia and corneal edema. He
      presented marked elevation of the intraocular pressure in both eyes (22 mmHg and
      26 mmHg, in the right eye and left eye respectively) associated with significant
      optic nerve cupping. Non-penetrating deep sclerectomy was performed for each eye,
      with effective reduction of the intraocular pressure during the first week
      postoperatively (11 mmHg and 7 mmHg in the right eye and left eye respectively).
      The right eye presented an isolated subhyaloid hemorrhage located in the pre
      macular area, persisting 3 weeks after the initial surgery and requiring pars
      plana vitrectomy to clear the visual axis. This uncommon complication was
      identified as decompression retinopathy. The intraocular pressure remained
      controlled in the normal range three years after initial surgery in both eyes,
      with reversal of optic disc cupping. CONCLUSIONS: Decompression retinopathy is a
      potential complication after non-penetrating deep sclerectomy in primary
      congenital glaucoma, requiring prompt treatment strategy to prevent potential
      organic amblyopia.

PMID- 30185154
TI  - Evaluation of Scheimpflug imaging parameters in blepharospasm and normal eyes.
AB  - BACKGROUND: To investigate changes in corneal elevation, pachymetry, and
      keratometry in discriminating between normal and blepharospasm eyes, as measured
      by the Pentacam rotating Scheimpflug camera. METHODS: This was a prospective,
      cross-sectional study. A total of 47 consecutive patients with a range of
      blepharospasm severity and 40 age- and sex- matched healthy subjects were
      included, one eye of each subject was randomly chosen for data analysis.
      Blepharospasm severity was evaluated using the Jankovic scale and categorized as
      mild, moderate, or severe. Corneal parameters were measured by the Pentacam
      rotating Scheimpflug camera to derive corneal tomography information. Various
      parameters regarding keratometry, elevation at the anterior and posterior corneal
      surface, pachymetric data, final D value, and topometric indices from the
      Pentacam software were recorded, and the relationship between the blink rate and
      corneal parameters was analyzed. Intraclass correlation coefficients (ICCs) were
      assessed to evaluate the repeatability of intraobserver. RESULTS: Increased
      topographic asymmetry was observed in moderate and severe blepharospasm. Front
      K1and front Km were significantly higher in cases of mild (P < 0.05), moderate (P
      < 0.0001), and severe (P < 0.0001) blepharospasm as compared with controls. Front
      K2, back K1, back K2, and back Km were significantly higher in cases of moderate
      (P < 0.01) and severe (P < 0.001) blepharospasm as compared with controls. For
      corneal topometric indices, both ISV and IVA were significantly increased in
      severe blepharospasm (P < 0.05). Radii minimum were significantly increased in
      cases of moderate and severe blepharospasm (P < 0.05).There were no differences
      in corneal elevation and corneal pharcymetric parameters among the four groups,
      except for front BFS, which was significantly different in blepharospasm groups
      (P < 0.05). Final D values were significantly higher in the severe blepharospasm
      (P < 0.01) group than that among controls. There were significant correlations
      between the blink rate and most corneal tomographic parameters. All parameters
      showed high reproducibility (ICC: 0.921-0.996) for normal and blepharospasm
      subjects. CONCLUSIONS: Blepharospasm may lead to a redistribution of the pressure
      applied by the lids over the cornea and, consequently, may result in corneal
      shape changes, which can be documented through corneal topography.

PMID- 30185153
TI  - Genome-wide transcriptome analysis using RNA-Seq reveals a large number of
      differentially expressed genes in a transient MCAO rat model.
AB  - BACKGROUND: The transient middle cerebral artery occlusion (tMCAO) model is used
      for studying the molecular mechanisms of ischemic damage and neuroprotection.
      Numerous studies have demonstrated the role of individual genes and associated
      signaling pathways in the pathogenesis of ischemic stroke. Here, the tMCAO model
      was used to investigate the genome-wide response of the transcriptome of rat
      brain tissues to the damaging effect of ischemia and subsequent reperfusion.
      RESULTS: Magnetic resonance imaging and histological examination showed that the
      model of focal ischemia based on endovascular occlusion of the right middle
      cerebral artery for 90 min using a monofilament, followed by restoration of the
      blood flow, led to reproducible localization of ischemic damage in the
      subcortical structures of the brain. High-throughput RNA sequencing (RNA-Seq)
      revealed the presence of differentially expressed genes (DEGs) in subcortical
      structures of rat brains resulting from hemisphere damage by ischemia after
      tMCAO, as well as in the corresponding parts of the brains of sham-operated
      animals. Real-time reverse transcription polymerase chain reaction expression
      analysis of 20 genes confirmed the RNA-Seq results. We identified 469 and 1939
      genes that exhibited changes in expression of > 1.5-fold at 4.5 and 24 h after
      tMCAO, respectively. Interestingly, we found 2741 and 752 DEGs under ischemia
      reperfusion and sham-operation conditions at 24 h vs. 4.5 h after tMCAO,
      respectively. The activation of a large number of genes involved in inflammatory,
      immune and stress responses, apoptosis, ribosome function, DNA replication and
      other processes was observed in ischemia-reperfusion conditions. Simultaneously,
      massive down-regulation of the mRNA levels of genes involved in the functioning
      of neurotransmitter systems was recorded. A Kyoto Encyclopedia of Genes and
      Genomes pathway enrichment analysis showed that dozens of signaling pathways were
      associated with DEGs in ischemia-reperfusion conditions. CONCLUSIONS: The data
      obtained revealed a global profile of gene expression in the rat brain sub-cortex
      under tMCAO conditions that can be used to identify potential therapeutic targets
      in the development of new strategies for the prevention and treatment of ischemic
      stroke.

PMID- 30185155
TI  - Incidence and cost of perioperative red blood cell transfusion for elective spine
      fusion in a high-volume center for spine surgery.
AB  - BACKGROUND: Spine fusion is a surgical procedure characterized by a significant
      perioperative bleeding, which often requires red blood cell (RBC) transfusion.
      METHODS: The incidence and the cost of RBC transfusion were evaluated in all
      patients undergoing elective surgery for spine fusion in our Institution, a high
      volume center for spine surgery, over a period of 3 years. The analysis
      specifically addressed the RBC transfusion need in all the different spine fusion
      procedures (atlanto-axial, cervical, dorsal, lumbar, revisions) with the
      different surgical approaches (anterior, posterior). RESULTS: During the 3 years
      of observation, a total of 1.882 elective spine fusions were performed. More than
      half of the procedures (n = 964) were posterior lumbar fusions. Overall, 5% of
      the patients (n = 103) required RBC transfusion. The cervical fusions were the
      procedures with the lowest percentage of RBC need (0-5%), while the dorsal and
      the lumbar ones, with the anterior approach, represented the procedures with the
      highest rate of transfusion (29% and 25% respectively). More than 60 % of the RBC
      units were employed in the instance of posterior lumbar fusion, while a variable
      1-10% of the units was used in each of the other procedures. The overall
      transfusion cost was of 46.000 euros, with a distribution of costs that
      paralleled the amount of units transfused for each procedure. CONCLUSIONS:
      Several surgical and patient factors may contribute to the perioperative blood
      loss. An accurate patient blood management, may efficiently decrease transfusion
      requirements and ultimately healthcare costs.

PMID- 30185156
TI  - Therapeutic effects of 3% diquafosol ophthalmic solution in patients with short
      tear film break-up time-type dry eye disease.
AB  - BACKGROUND: To investigate therapeutic effects of topical diquafosol tetrasodium
      3% ophthalmic solution in patients with short tear film break-up time (TFBUT)
      type dry eye (DE). METHODS: The prospective study was performed in 70 eyes of 70
      patients with short TFBUT-type DE. Diagnosis of short TFBUT-type DE was made
      based on the presence of DE symptoms, TFBUT value <=5 s, corneoconjunctival
      staining score <= 2 (on a scale of 0 to 4), and Schirmer I value > 5 mm. Patients
      with systemic immunologic disorders or ocular graft-versus-host disease were
      excluded. Before and after instillation of 3% diquafosol ophthalmic solution six
      times per day for 4 weeks, subjective DE symptoms, TFBUT, corneoconjunctival
      staining score, and Schirmer I value were examined and compared. Also,
      demographic factors were compared between patients who showed improvement in each
      DE parameter by treatment and those who did not. RESULTS: Four-week treatment
      with 3% diquafosol ophthalmic solution significantly improved DE symptoms (p <
      0.0001), increased TFBUT (p < 0.0001), and reduced corneoconjunctival staining
      scores (p < 0.0001). Schirmer I values were not changed by treatment. The age of
      patients who showed improvement in subjective DE symptoms after treatment was
      significantly lower than that of patients who did not (53.4 +/- 27.5 vs. 63.3 +/-
      13.9 years, p = 0.012). Ocular side effects developed in 3 patients (4.3%),
      including conjunctival chemosis (n = 1) and persistent stinging sensation (n =
      2). CONCLUSIONS: Diquafosol tetrasodium 3% ophthalmic solution is effective in
      improving subjective symptoms and tear film stability in short TFBUT-type DE
      patients. TRIAL REGISTRATION: The study was retrospectively registered on
      Clinical Research Information Service (CRiS), Republic of Korea. TRIAL
      REGISTRATION NUMBER: KCT0003134 . Date of registration: 2018-08-15.

PMID- 30185157
TI  - Correlation between family physician's direct advice and pneumococcal vaccination
      intention and behavior among the elderly in Japan: a cross-sectional study.
AB  - BACKGROUND: Vaccination is an important element of health maintenance in family
      medicine. The 23-valent pneumococcal polysaccharide vaccine (PPSV23) is highly
      recommended for the elderly, but its uptake is low in Japan. Primary care system
      remains under development and preventive services tend to be neglected in the
      Japanese medical practice. The study aims to investigate the association between
      family physician's recommendations for PPSV23 during outpatient care and PPSV23
      vaccination intention and behavior in the elderly. METHOD: We conducted a cross
      sectional study with a questionnaire at a family medicine clinic in a rural area
      in Japan. The participants were over the age of 65 without dementia who had
      maintained a continuity with the clinic. The questionnaire inquired PPSV23
      vaccination status, family physician's advice for PPSV23, socio-demographics, and
      the constructs in the Health Belief Model. We defined those who had had
      vaccination intention and behavior as "PPSV23 vaccinated group" and those who had
      no vaccination and uncertainty about being or no intention to be vaccinated in
      the future as "PPSV23 unvaccinated group." We used chi-square test for
      correlation between physician's advice and PPSV23 vaccination/intention,
      univariate and multivariate logistic regression analysis for factors related to
      the vaccination/intention, and descriptive analysis for reasons for reluctance to
      the vaccination. RESULTS: We analyzed 209 valid responses. There were 142
      participants in the PPSV23 vaccinated group and 67 in the PPSV23 unvaccinated
      group. The PPSV23 vaccination group was more likely to have had their physician's
      advice (80.2% vs 21.3%, p < 0.001). Multivariate logistic regression analysis
      showed a significant association between PPSV23 vaccination and their physician's
      recommendation (OR 8.50, 95%CI 2.8-26.0), awareness of PPSV23 (OR 8.52, 95%CI 2.1
      35.0), and the perceived effectiveness of PPSV23 (OR 4.10, 95%CI 1.2-13.9). The
      reasons for reluctance to get vaccinated included lack of understanding of
      PPSV23, lack of physician's recommendations, and concerns about side effects of
      PPSV23. CONCLUSION: Family physician's recommendation was positively correlated
      with PPSV23 vaccination intention and behavior in the elderly. This reinforces
      the importance of providing preventive services during time-constrained
      outpatient care, even in medical systems where it is undervalued.

PMID- 30185158
TI  - Analysis of evolution and genetic diversity of sweetpotato and its related
      different polyploidy wild species I. trifida using RAD-seq.
AB  - BACKGROUND: Sweetpotato (Ipomoea batatas (L.) Lam.) is one of the most important
      crops from the family of Convolvulaceae. It is widely reported that cultivated
      sweetpotato was originated from Ipomoea trifida. However, diploid, tetraploid and
      hexaploid I. trifida were found in nature. The relationship, between them, and
      among them and sweetpotato, is remaining unclear. RESULTS: In the present study,
      we detected the genome diversity and relationship of sweetpotato and different
      polyploidy types I. trifida using Restriction-site Associated DNA Sequencing (RAD
      seq). A total of 38,605 RAD-tags containing 832,204 SNPs had been identified.
      These tags were annotated using five public databases, about 11,519 tags were
      aligned to functional genes in various pathways. Based on SNP genotype,
      phylogenetic relation analysis results confirmed that cultivated sweetpotato has
      a closer relationship with I. trifida 6* than with I. trifida 4X and I. trifida
      2*. Besides, 5042 SSRs were detected in I. trifida 6*, and 3202 pairs of high
      quality SSR primers were developed. A total of 68 primers were randomly selected
      and synthesized, of which 61 were successfully amplified. CONCLUSION: These
      results provided new evidence that cultivated sweetpotato originated from I.
      trifida 6*, and that I. trifida 6* evolved from I. trifida 4X and I. trifida 2*.
      Therefore, using I. trifida 6* as the model plant of sweetpotato research should
      be more practical than using I. trifida 2* in the future. Meanwhile, sequence
      information and markers from the present study will be helpful for sweetpotato
      and I. trifida studies in the future.

PMID- 30185159
TI  - Ultrasound-guided phrenic nerve block for intraoperative persistent hiccups: a
      case report.
AB  - BACKGROUND: Continuous hiccups during surgery not only affect the surgical
      procedure, they can also cause adverse effects for the patient. Apart from active
      investigation of the cause of the hiccups, their timely termination is also
      necessary. CASE PRESENTATION: We reported a case of a 70-year-old woman with
      continuous intraoperative hiccups that appeared during vaginal hysterectomy under
      low continuous epidural anesthesia. After the ineffectiveness CO2 repeated
      inhalation and intravenous administration of chlorpromazine and
      methoxychlorpromide, we performed unilateral phrenic nerve block under ultrasound
      guidance. Hiccups were terminated without any related complications. CONCLUSIONS:
      During intraoperative continuous hiccups, ultrasound guided phrenic nerve block
      may be a suitable treatment option when physical methods and drug therapy are not
      effective. However, given the absence of a vital risk related to hiccups, this
      block should imply the complete absence of any respiratory contraindication and a
      prolonged postoperative respiratory monitoring.

PMID- 30185160
TI  - The relationship between motor proficiency and reading ability in Year 1
      children: a cross-sectional study.
AB  - BACKGROUND: Movement and physical activity is crucial to brain development and
      has a positive impact on the ability to learn. With children spending a large
      portion of their time in the school setting, physical activity and the
      development of motor skills in this environment may not only impact their overall
      development but may also influence their learning. The aim of this study was to
      investigate relationships between motor proficiency and reading skills in Year-1
      children. METHODS: A cross-sectional study with a single class of Year-1 students
      (n = 24: mean age = 6.07 +/- 0.35 years). Assessments included; a) Process
      Assessment of the Learner (PAL-II) - Diagnostics for Reading and Writing (reading
      components only); b) Bruininks-Oseretsky-Test-of-Motor-Proficiency (BOT2); c)
      parent-reported height/weight and; d) Preparatory Year academic reports. The PAL
      II was individually administered. The BOT2 was administered in small groups.
      Parent-reported height and weight measurements as well as Preparatory Year
      reports provided by the school Principal were obtained for each participant.
      RESULTS: Significant negative relationships were obtained between Year-1
      children's total motor proficiency and silent reading ability (r = -.53 to -.59,
      p <= .01). While not significant for female students, the relationships were
      significant and strongly correlated for male students (r = -.738 to -.810, p <=
      .001). Children with low-average English grades demonstrated a strong positive
      relationship between motor proficiency and pre-reading skills, essential to
      functional reading (r = .664., p = .04 to r = .716, p = .04). CONCLUSION: For
      children with low-average English grades, the strong, positive relationship
      between motor proficiency and pre-reading skills suggests that this population
      may benefit from additional motor proficiency skills. Blending of motor skills
      within the English curriculum may benefit both of these sub-groups within a
      classroom environment.

PMID- 30185161
TI  - Provider and client perspectives on maternity care in Namibia: results from two
      cross-sectional studies.
AB  - BACKGROUND: Disrespectful and abusive maternity care is a complex phenomenon. In
      Namibia, HIV and high maternal mortality ratios make it vital to understand
      factors affecting maternity care quality. We report on two studies commissioned
      by Namibia's Ministry of Health and Social Services. A health worker study
      examined cultural and structural factors that influence maternity care workers'
      attitudes and practices, and a maternal and neonatal mortality study explored
      community perceptions about maternity care. METHODS: The health worker study
      involved medical officers, matrons, and registered or enrolled nurses working in
      Namibia's 35 district and referral hospitals. The study included a survey (N =
      281) and 19 focus group discussions. The community study conducted 12 focus
      groups in five southern regions with recently delivered mothers and relatives.
      RESULTS: Most participants in the health worker study were experienced maternity
      care nurses. One-third (31%) of survey respondents reported witnessing or knowing
      of client mistreatment at their hospital, about half (49%) agreed that "sometimes
      you have to yell at a woman in labor," and a third (30%) agreed that pinching or
      slapping a laboring woman can make her push harder. Nurses were much more likely
      to agree with these statements than medical officers. Health workers' commitment
      to babies' welfare and stressful workloads were the two primary reasons cited to
      justify "harsh" behaviors. Respondents who were dissatisfied with their workload
      were twice as likely to approve of pinching or slapping. Half of the nurses
      surveyed (versus 14% of medical officers) reported providing care above or
      beneath their scope of work. The community focus group study identified 14
      negative practices affecting clients' maternity care experiences, including both
      systemic and health-worker-related practices. CONCLUSIONS: Namibia's public
      sector hospital maternity units confront health workers and clients with
      structural and cultural impediments to quality care. Negative interactions
      between health workers and laboring women were reported as common, despite high
      health worker commitment to babies' welfare. Key recommendations include
      multicomponent interventions that address heavy workloads and other structural
      factors, educate communities and the media about maternity care and health
      workers' roles, incorporate client-centered care into preservice education, and
      ensure ongoing health worker mentoring and supervision.

PMID- 30185162
TI  - Childbirth preferences and related fears - comparison between Norway and Israel.
AB  - BACKGROUND: Fear of childbirth (FOC) could have significant impact on women's
      childbearing choices and experience. Culture affects the way women conceptualize
      childbirth, influencing the fears and expectations they may hold in relation to
      it. In the current study, we examined differences in childbirth preferences of
      cesarean section and use of epidural analgesia between Norwegian and Israeli
      pregnant women. Later, we used the Norwegian six-factor solution of the widely
      used Wijma Delivery Expectancy Questionnaire (W-DEQ-A) to compare levels of the
      different FOC factors. Finally, we investigated differences in the associations
      between FOC and childbirth preferences between the two countries. METHODS:
      Secondary analysis of two large surveys. Women from Israel (n = 490) and Norway
      (n = 2918) were recruited during prenatal check-ups in community clinics and a
      university hospital. At around 32 weeks of gestation, all participants filled out
      questionnaires, including the W-DEQ-A. Statistical analysis included exploratory
      factor analysis, confirmatory factor analysis, M/ANOVA, Spearman's Rho and
      Fisher's Z tests for the significance of the difference between independent
      correlations. RESULTS: The Norwegian six-factor solution of the W-DEQ fit well
      with the Israeli data. Norwegian women were more concerned about loneliness,
      feeling less self-efficacy, negatively appraising birth, and lacking positive
      anticipation. Israeli women were more concerned about negative outcomes for the
      child and experienced greater general fear and fear of pain. Norwegian women
      preferred more cesarean sections compared to Israeli women, who preferred more
      epidural use than Norwegians. FOC factors were more strongly related to
      childbirth preferences among Norwegians. CONCLUSIONS: Cultural differences
      between Israel and Norway are reflected by the differences seen in the levels of
      fear reported across the six factors. In Israel, birth culture is very
      medicalized, motherhood is highly revered, and there is an emphasis on having
      "perfect babies". In contrast, Norwegian women have fewer children, and birth is
      considered more natural. This could explain why Israeli women were more concerned
      that their child might be harmed during birth, while Norwegian women were more
      concerned with the physical and emotional expectations of birth.

PMID- 30185163
TI  - Care avoidance among homeless people and access to care: an interview study among
      spiritual caregivers, street pastors, homeless outreach workers and formerly
      homeless people.
AB  - BACKGROUND: Because of their poor health and social vulnerability, homeless
      people require specific care. However, due to care avoidance, homeless people are
      often not involved in care. This study aims to get insights into reasons for and
      kinds of care avoidance among homeless people and to provide suggestions to reach
      this target group. METHODS: Semi-structured individual interviews were conducted
      among street pastors (n = 9), spiritual caregivers (n = 9), homeless outreach
      workers (n = 7) and formerly homeless people (n = 3). Participants were recruited
      by purposive sampling in the four major cities in the Netherlands (Amsterdam,
      Utrecht, Rotterdam, The Hague). The verbatim transcripts were analysed using
      thematic analysis. RESULTS: The term care avoidance was perceived as
      stigmatizing. Care avoidance is found to be related to characteristics of the
      homeless person (e.g. having complex problems, other priorities) as well as of
      the system (e.g. complex system, conditions and requirements of organizations).
      The person-related characteristics suggestions to involve homeless persons
      include tailoring care and building relationships, which might even be
      prioritised over starting care interventions. Setting limits on behaviour without
      rejecting the person, and an attitude reflecting humanity, dignity and equality
      were also important factors in making care more accessible and lasting. As
      regards system-related characteristics, the suggestions include clear information
      and communication to homeless people who avoid care as being crucial in order to
      make care more accessible. Other suggestions include quiet and less busy
      shelters, a non-threatening attitude and treatment by professionals, self
      reflection by professionals and finally a change of policy and legislation
      regarding available time. CONCLUSIONS: Reasons for care avoidance can be found in
      the interplay between both the individual and the system; measures to reduce care
      avoidance should be taken at both levels. These measures are centred on lowering
      the barriers to care inter alia by incorporating building trust and understanding
      into the care provided.

PMID- 30185164
TI  - Co-occurrence of carbapenemase encoding genes in Acinetobacter baumannii, a dream
      or reality?
AB  - BACKGROUND: Acinetobacter baumannii is an important opportunistic pathogen that
      is rapidly evolving towards multidrug resistance and is responsible for life
      threatening infections. Carbapenems are commonly used to treat A. baumannii
      infections but the emergence of carbapenemase encoding genes, such as blaOXA-23
      like, blaOXA-24-like, blaOXA-58-like, and blaNDM has been reported. Moreover,
      several studies have reported the co-occurrence of two distinct carbapenemases in
      some isolates. The aim of the present study is to demonstrate whether the
      phenomenon of co-occurrence of two distinct carbapenemase encoding genes in a
      single isolate still exists. RESULTS: We studied six strains of A. baumannii
      including one harboring blaOXA-23-like and blaOXA-24-like genes and five with
      blaOXA-23-like and blaNDM genes. One colony of each strain was inoculated in
      sterile water and diluted ten-fold. Each dilution was cultivated on trypticase
      soy agar plates for 24 h at 37  degrees C and the isolated bacteria were
      analyzed. For two of the six tested strains, we identified two different
      populations of A. baumannii, each with a different carbapenemase, genes encoding
      aminoglycoside modifying enzymes, resistance phenotype, and clonal type. In
      addition, the two different populations had the same aspect on the agar plate.
      CONCLUSIONS: Here, we demonstrate that A. baumannii infections could be linked to
      multiple clones harboring different carbapenemase encoding genes in the same
      sample. In addition, we describe an easy method of verifying the presence of co
      occurrence of carbapenemase in one isolate.

PMID- 30185165
TI  - Early intervention at home in infants with congenital brain lesion with CareToy
      revised: a RCT protocol.
AB  - BACKGROUND: Congenital brain lesions expose infants to be at high-risk for being
      affected by neurodevelopmental disorders such as cerebral palsy (CP). Early
      interventions programs can significantly impact and improve their
      neurodevelopment. Recently, in the framework of the European CareToy (CT) Project
      ( www.caretoy.eu ), a new medical device has been created to deliver an early,
      intensive, customized, intervention program, carried out at home by parents but
      remotely managed by expert and trained clinicians. Reviewing results of previous
      studies on preterm infants without congenital brain lesion, the CT platform has
      been revised and a new system created (CT-R). This study describes the protocol
      of a randomised controlled trial (RCT) aimed to evaluate, in a sample of infants
      at high-risk for CP, the efficacy of CT-R intervention compared to the Infant
      Massage (IM) intervention. METHODS/DESIGN: This RCT will be multi-centre, paired
      and evaluator-blinded. Eligible subjects will be preterm or full-term infants
      with brain lesions, in first year of age with predefined specific gross motor
      abilities. Recruited infants will be randomized into CT-R and IM groups at
      baseline (T0). Based on allocation, infants will perform an 8-week programme of
      personalized CareToy activities or Infant Massage. The primary outcome measure
      will be the Infant Motor Profile. On the basis of power calculation, it will
      require a sample size of 42 infants. Moreover, Peabody Developmental Motor Scales
      Second Edition, Teller Acuity Cards, standardized video-recordings of parent
      infant interaction and wearable sensors (Actigraphs) will be included as
      secondary outcome measures. Finally, parents will fill out questionnaires (Bayley
      Social-Emotional, Parents Stress Index). All outcome measures will be carried out
      at the beginning (T0) and at end of 8-weeks intervention period, primary endpoint
      (T1). Primary outcome and some secondary outcomes will be carried out also after
      2 months from T1 and at 18 months of age (T2 and T3, respectively). The Bayley
      Cognitive subscale will be used as additional assessment at T3. DISCUSSION: This
      study protocol paper is the first study aimed to test CT-R system in infants at
      high-risk for CP. This paper will present the scientific background and trial
      methodology. TRIAL REGISTRATION: NCT03211533 and NCT03234959 (
      www.clinicaltrials.gov ).

PMID- 30185166
TI  - The genome of Naegleria lovaniensis, the basis for a comparative approach to
      unravel pathogenicity factors of the human pathogenic amoeba N. fowleri.
AB  - BACKGROUND: Members of the genus Naegleria are free-living eukaryotes with the
      capability to transform from the amoeboid form into resting cysts or moving
      flagellates in response to environmental conditions. More than 40 species have
      been characterized, but only Naegleria fowleri (N. fowleri) is known as a human
      pathogen causing primary amoebic meningoencephalitis (PAM), a fast progressing
      and mostly fatal disease of the central nervous system. Several studies report an
      involvement of phospholipases and other molecular factors, but the mechanisms
      involved in pathogenesis are still poorly understood. To gain a better
      understanding of the relationships within the genus of Naegleria and to
      investigate pathogenicity factors of N. fowleri, we characterized the genome of
      its closest non-pathogenic relative N. lovaniensis. RESULTS: To gain insights
      into the taxonomy of Naegleria, we sequenced the genome of N. lovaniensis using
      long read sequencing technology. The assembly of the data resulted in a 30 Mb
      genome including the circular mitochondrial sequence. Unravelling the
      phylogenetic relationship using OrthoMCL protein clustering and maximum
      likelihood methods confirms the close relationship of N. lovaniensis and N.
      fowleri. To achieve an overview of the diversity of Naegleria proteins and to
      assess characteristics of the human pathogen N. fowleri, OrthoMCL protein
      clustering including data of N. fowleri, N. lovaniensis and N. gruberi was
      performed. GO enrichment analysis shows an association of N. fowleri specific
      proteins to the GO terms "Membrane" and "Protein Secretion." CONCLUSION: In this
      study, we characterize the hitherto unknown genome of N. lovaniensis. With the
      description of the 30 Mb genome, a further piece is added to reveal the complex
      taxonomic relationship of Naegleria. Further, the whole genome sequencing data
      confirms the hypothesis of the close relationship between N. fowleri and N.
      lovaniensis. Therefore, the genome of N. lovaniensis provides the basis for
      further comparative approaches on the molecular and genomic level to unravel
      pathogenicity factors of its closest human pathogenic relative N. fowleri and
      possible treatment options for the rare but mostly fatal primary
      meningoencephalitis.

PMID- 30185167
TI  - Health promoting lifestyle of university students in Saudi Arabia: a cross
      sectional assessment.
AB  - BACKGROUND: College is a critical time where students are more prone to engage in
      risky health behaviors known to negatively affect well-being, such as physical
      inactivity, stress, and poor dietary habits. A health promoting lifestyle is an
      important determinant of health status and is recognized as a major factor for
      the maintenance and improvement of health. This study was designed to assess the
      health-promoting lifestyle of students in health colleges and non-health colleges
      in Saudi Arabia. METHODS: A total of 1656 students participated in this
      descriptive cross-sectional study. Data gathering was conducted from November
      2016 to February 2017 at King Saud University. Participating students completed a
      self-reported questionnaire that included questions regarding their demographic
      characteristics and their health-promoting behaviors. RESULTS: The majority of
      participants were females (70.4%), 20% of the participants were overweight and
      11.3%, were obese. The analysis showed that there was a significant difference
      between health colleges and non-health colleges with regards to the factor of
      health responsibility. Students at both schools were found to have an inadequate
      level of adherence to recommendations regarding physical activity and healthy
      eating habits. The analysis also found that majority of the students in both
      colleges do not attend educational programs on health care. The model shows that
      gender, type of college, year in school, and family structure were significant
      predictors of the health lifestyle of students in Saudi Arabia. CONCLUSION: The
      results of the current study indicate that university students are leading
      unhealthy lives, where the majority of them have unhealthy eating habits and poor
      physical activity level. Universities are ideal settings for implementing health
      promotion programs. Therefore, planning and implementing programs to motivate
      students to be more responsible for their own health, to engage more in physical
      activity, and to practice healthy eating habits and other forms of wellness are
      of paramount importance.

PMID- 30185168
TI  - Relapse of chronic melioidosis in a paediatric cystic fibrosis patient: first
      case report from Malaysia.
AB  - BACKGROUND: Burkholderia pseudomallei is the causative agent of melioidosis,
      which is a potentially life threatening disease endemic in Southeast Asian
      countries. In Malaysia, cystic fibrosis (CF) is an uncommon condition. The
      association between CF and B.pseudomallei infections has been reported
      previously. However, this is the first case report of a pediatric melioidosis
      relapse and co-infection with other Gram-negative bacteria in Malaysia. CASE
      PRESENTATION: A 14-year-old Chinese Malaysian boy presented with a history of
      recurrent pneumonia, poor growth and steatorrhoea since childhood, and was
      diagnosed with CF. B. pseudomallei was cultured from his sputum during three
      different admissions between 2013 and 2016. However, the patient succumbed to end
      stage of respiratory failure in 2017 despite antibiotics treatment against
      B.pseudomallei. The isolates were compared using multilocus-sequence typing and
      repetitive-element polymerase chain reaction (PCR), and confirmed that two of the
      isolates were of same sequence type, which may indicate relapse. CONCLUSIONS: CF
      patients should be aware of melioidosis in endemic regions, as it is an emerging
      infectious disease, especially when persistent or recurrent respiratory symptoms
      and signs of infection occur. The high prevalence rates of melioidosis in
      Malaysia warrants better management options to improve quality of life, and life
      expectancy in patients with CF. Travel activities to endemic regions should also
      be given more consideration, as this would be crucial to identify and initiate
      appropriate empiric treatment.

PMID- 30185169
TI  - Ten years of simulation-based shoulder dystocia training- impact on obstetric
      outcome, clinical management, staff confidence, and the pedagogical practice - a
      time series study.
AB  - BACKGROUND: To assess the impact of 10 years of simulation-based shoulder
      dystocia training on clinical outcomes, staff confidence, management, and to
      scrutinize the characteristics of the pedagogical practice of the simulation
      training. METHODS: In 2008, a simulation-based team-training program (PROBE) was
      introduced at a medium sized delivery unit in Linkoping, Sweden. Data concerning
      maternal characteristics, management, and obstetric outcomes was compared between
      three groups; prePROBE (before PROBE was introduced, 2004-2007), early postPROBE
      (2008-2011) and late postPROBE (2012-2015). Staff responded to an electronic
      questionnaire, which included questions about self-confidence and perceived sense
      of security in acute obstetrical situations. Empirical data from the pedagogical
      practice was gathered through observational field notes of video-recordings of
      maternity care teams participating in simulation exercises and was further
      analyzed using collaborative video analysis. RESULTS: The number of diagnosed
      shoulder dystocia increased from 0.9/1000 prePROBE to 1.8 and 2.5/1000 postPROBE.
      There were no differences in maternal characteristics between the groups. The
      rate of brachial plexus injuries in deliveries complicated with shoulder dystocia
      was 73% prePROBE compared to 17% in the late postPROBE group (p > 0.05). The
      dominant maneuver to solve the shoulder dystocia changed from posterior arm
      extraction to internal rotation of the anterior shoulder between the pre and
      postPROBE groups. The staff questionnaire showed how the majority of the staff
      (48-62%) felt more confident when handling a shoulder dystocia after PROBE
      training. A model of facilitating relational reflection adopted seems to provide
      ways of keeping the collaboration and learning in the interprofessional team
      clearly focused. CONCLUSIONS: To introduce and sustain a shoulder dystocia
      training program for delivery staff improved clinical outcome. The impaired
      management and outcome of this rare, emergent and unexpectedly event might be
      explained by the learning effect in the debriefing model, clearly focused on the
      team and related to daily clinical practice.

PMID- 30185170
TI  - Rare Shewanella spp. associated with pulmonary and bloodstream infections of
      cancer patients, China: a case report.
AB  - BACKGROUND: Members of Shewanella species are opportunistic pathogens that are
      found in marine environments. Currently more than sixty species have been
      identified, whereas the most commonly clinical cases associated with Shewanella
      species have involved only two species, i.e., S. algae and S. putrefaciens. We
      present two cases of pulmonary and bloodstream infections caused by two rare
      Shewanella spp. strains from patients of gastrointestinal cancer. CASE
      PRESENTATION: Two male patients with a history of gastrointestinal cancer
      presented to hospital with pulmonary and bloodstream infections, respectively.
      The infective pathogens of both cases were primarily isolated and identified as
      Shewanella algae (case I) and Shewanella putrefaciens (case II) by phenotypic
      features and VITEK 2 system, but they were further confirmed as Shewanella
      haliotis and Shewanella upenei by 16S rRNA gene sequence analysis. The major
      bacterial composition of the bronchoalveolar lavage in case I was also identified
      as Shewanella by 16S rRNA amplicon sequencing analysis. Antimicrobial
      susceptibility testing showed that the two strains had broad susceptibility, but
      S. haliotis in the case I was resistant to ciprofloxacin and levofloxacin and S.
      upenei in the case II was intermediate to imipenem, piperacillin/tazobactam and
      ciprofloxacin. CONCLUSIONS: To the best of our knowledge, this is the first cases
      of the pulmonary and bloodstream infections caused by Shewanella spp. from
      clinical patients in mainland China. Shewanella as a potential pathogen in China
      should not be ignored.

PMID- 30185171
TI  - Psychometrics of the self-efficacy for physical activity scale among a Latina
      women sample.
AB  - BACKGROUND: Even though Latinos have become a priority population for the
      promotion of physical activity in the United States, several widely used scales
      in physical activity promotion research have not been validated among this
      population, particularly in Spanish. This study aims to assess the validity and
      other psychometrics of the Self-Efficacy for Physical Activity scale among a
      sample of Spanish-speaking Latina women who participated in the Pasos Hacia La
      Salud intervention. We also explored alternatives for scale simplification.
      METHODS: Data from 205 women corresponding to baseline, 6-month, and 12-month
      time points were analyzed. Internal consistency was assessed. A series of
      Spearman correlations, t-tests, linear regressions, and logistic regressions were
      used to assess the concurrent and predictive validity of the Self Efficacy for
      Physical Activity scale against both self-report and accelerometer-measured
      physical activity, using both continuous and categorical outcome data. Item
      Response Theory and factor analysis methods were used to explore alternatives to
      simplify the scale. Psychometric tests were repeated with the simplified scale.
      RESULTS: Cronbach's alpha for the original scale was .72, .76, and .78 for
      baseline, 6-month, and 12-month data respectively. All concurrent validity tests
      conducted with 6-month and 12-month data, but not with baseline data, were
      statistically significant. Self-efficacy at 6 months was also predictive of
      physical activity at 12 months for all tests except one. Based on plots of Option
      Characteristic Curves, a modified version of the scale was created. Psychometric
      results of the modified scale were similar to those of the original scale.
      CONCLUSIONS: This study confirmed the scale's reliability and validity, and
      revealed that the scale's accuracy improves when some response items are
      collapsed, which is an important finding for future research among populations
      with low literacy levels.

PMID- 30185174
TI  - Encouraging residents' professional development and career planning: the role of
      a development-oriented performance assessment.
AB  - BACKGROUND: Current postgraduate medical training programmes fall short regarding
      residents' development of generic competencies (communication, collaboration,
      leadership, professionalism) and reflective and deliberate practice. Paying
      attention to these non-technical skills in a structural manner during
      postgraduate training could result in a workforce better prepared for practice. A
      development-oriented performance assessment (PA), which assists residents with
      assessment of performance and deliberately planned learning activities, could
      potentially contribute to filling this gap. This study aims to explore residents
      experiences with the PA. METHODS: We conducted a qualitative interview study with
      16 residents from four different medical specialties who participated in the PA,
      scheduled halfway postgraduate training. The PA was conducted by an external
      facilitator, a psychologist, and focused specifically on professional development
      and career planning. Residents were interviewed 6 months after the PA. Data were
      analysed using the framework method for qualitative analysis. RESULTS: Residents
      found the PA to be of additional value for their training. The overarching merit
      was the opportunity to evaluate competencies not usually addressed in workplace
      based assessments and progress conversations. In addition, the PA proved a
      valuable tool for assisting residents with reflecting upon their work and
      formulating their learning objectives and activities. Residents reported
      increased awareness of capacity, self-confidence and enhanced feelings of career
      ownership. An important factor contributing to these outcomes was the
      relationship of trust with the facilitator and programme director. CONCLUSION:
      The PA is a promising tool in fostering the development of generic competencies
      and reflective and deliberate practice. The participating residents, facilitator
      and programme directors were able to contribute to a safe learning environment
      away from the busy workplace. The facilitator plays an important role by
      providing credible and informative feedback. Commitment of the programme director
      is important for the implementation of developmental plans and learning
      activities.

PMID- 30185172
TI  - Protocol for a Delphi consensus exercise to identify a core set of criteria for
      selecting health related outcome measures (HROM) to be used in primary health
      care.
AB  - BACKGROUND: Promoting the collection and use of health related outcome measures
      (HROM) in daily practice has long been a goal for improving and assessing the
      effectiveness of care provided to patients. However, there has been a lack of
      consensus on what criteria to use to select outcomes or instruments, particularly
      in the context of primary health care settings where patients present with
      multiple concurrent health conditions and interventions are whole-health and
      person-focused. The purpose of this proposed study is to undertake a formal
      consensus exercise to establish criteria for selecting HROM (including patient
      reported (PRO or PROM), observer-reported (ObsR)), clinician-reported (ClinRO)
      and performance related outcomes (PerfO) for use in shared decision-making, or in
      assessing, screening or monitoring health status in primary health care settings.
      METHODS: A Delphi consensus online survey will be developed. Criteria for the
      Delphi panel participants to consider were selected from a targeted literature
      search. These initial criteria (n = 35) were grouped into four categories within
      which items will be presented in the Delphi survey, with the option to suggest
      additional items. Panel members invited to participate will include primary
      health care practitioners and administrators, policy-makers, researchers, and
      experts in HROM development; patients will be excluded. Standard Delphi
      methodology will be employed with an expectation of at least 3 rounds to achieve
      consensus (75% agreement). As the final list of criteria for selecting HROM
      emerges, panel members will be asked to provide opinions about potential
      weighting of items. The Delphi survey was approved by the Ethics Committee in the
      Faculty of Health Sciences at McMaster University. DISCUSSION: Previous
      literature establishing criteria for selecting HROM were developed with a focus
      on patient reported outcomes, psychological/ behavioural outcomes or outcomes for
      minimum core outcome sets in clinical trials. Although helpful, these criteria
      may not be applicable and feasible for application in a primary health care
      context where patients with multi-morbidity and complex interventions are typical
      and the constraints of providing health services differ from those in research
      studies. The findings from this Delphi consensus study will address a gap for
      establishing consensus on criteria for selecting HROM for use across primary
      health care settings.

PMID- 30185173
TI  - Comparative efficacy and safety between amisulpride and olanzapine in
      schizophrenia treatment and a cost analysis in China: a systematic review, meta
      analysis, and cost-minimization analysis.
AB  - BACKGROUND: Amisulpride was introduced into China in 2010 as a second-generation
      atypical antipsychotic, while olanzapine has been on the market since 1999 as one
      of the leading treatments for schizophrenia in China. Since more Chinese patients
      are gaining access to amisulpride, the study aims to compare the efficacy,
      safety, and costs between amisulpride and olanzapine for schizophrenia treatment
      in China. METHODS: PubMed, Embase, the Cochrane library, China National Knowledge
      Infrastructure (CNKI) and WanFang database were systematically searched for
      randomized controlled trials (RCTs) up to July 2018. The Cochrane Risk of Bias
      tool was utilized to assess the quality of included studies. A meta-analysis was
      performed to compare the efficacy and safety of amisulpride and olanzapine,
      followed by a cost-minimization analysis using local drug and medical costs
      reported in China. RESULTS: Twenty RCTs with 2000 patients were included in the
      systematic review. There were no significant differences between amisulpride and
      olanzapine on efficacy measures based on scores from the Positive and Negative
      Syndrome Scale, the Scale for the Assessment of Negative Symptoms, the Brief
      Psychiatric Rating Scale and the Clinical Global Impressions-Severity or
      Improvement. For safety outcomes, amisulpride was associated with lower fasting
      blood glucose and less abnormal liver functions as well as significantly lower
      risks of weight gain, constipation, and somnolence; olanzapine was associated
      with significantly lower risks of insomnia and lactation/amenorrhea/sexual
      hormone disorder. No significant differences were found in risks of
      extrapyramidal symptoms (EPS), tremor, akathisia, abnormal corrected QT interval.
      Cost-minimization analysis showed that amisulpride was likely to be a cost-saving
      alternative in China, with potential savings of 1358 Chinese Yuan (CNY) per
      patient for a three-month schizophrenia treatment compared with olanzapine.
      CONCLUSION: As the first meta-analysis and cost-minimization analysis comparing
      the efficacy, safety and cost of amisulpride and olanzapine within a Chinese
      setting, the study suggests that amisulpride may be an effective, well-tolerated,
      and cost-saving antipsychotic drug alternative in China.

PMID- 30185175
TI  - Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for
      pseudomyxoma peritonei in a liver-transplanted patient: a case report.
AB  - BACKGROUND: Diagnostic work-ups in transplanted immunosuppressed patients are a
      challenge as non-specific findings may be interpreted as transplant-related
      complications. If the disease in question is rare and slowly developing like
      pseudomyxoma peritonei (PMP), it is even more difficult. Cytoreductive surgery
      (CRS) and subsequent hyperthermic intraperitoneal chemotherapy (HIPEC) is the
      recommended treatment for PMP even with extensive peritoneal spread. CRS-HIPEC
      for PMP after liver transplantation (LTX) has not been described before. CASE
      PRESENTATION: A 48-year-old female patient with end-stage primary sclerosing
      cholangitis (PSC) underwent orthotopic LTX and subsequent pancreaticoduodenectomy
      after the finding of cholangiocarcinoma in situ in the native common bile duct.
      Ten years after the transplantation, she developed symptoms and signs suspected
      to represent graft-related complications. An extensive work-up revealed PMP. Upon
      reassessment, a cystic mass near the coecum could be seen on computed tomography
      scan 1 year after transplantation. The multidisiplinary team was hesitant to
      accept the patient for CRS-HIPEC because of extensive PMP and possible risk to
      the graft. However, she was eventually accepted and underwent the procedure. The
      Peritoneal Cancer Index (PCI) was 28 of 39, and surgical debulking was performed
      followed by HIPEC. The transplant control 2 months after surgery showed no harm
      to the graft. CONCLUSIONS: Previous LTX should not exclude the possibility for
      CRS-HIPEC in PMP, even with extensive burden of disease.

PMID- 30185176
TI  - The multidisciplinary treatment of osteosarcoma of the proximal tibia: a
      retrospective study.
AB  - BACKGROUND: Survival and reconstruction constitute important challenges in
      multimodal treatment of osteosarcoma of the proximal tibia. The purpose of this
      study was to assess the efficacy and prognosis of neoadjuvant chemotherapy and
      custom-designed endoprosthetic arthroplasty. METHODS: A total of 69 patients with
      osteosarcoma of the proximal tibia were evaluated, including 43 males and 26
      females, treated with multidisciplinary limb-salvage remedy from October 2003 to
      December 2013. They were at least 12 years old (mean, 20 years; range, 12-57
      years). The gap between tumor and main artery/nerve was showed in MRI. Mean
      follow up was 69.5 months (range, 9-144 months). Kaplan-Meier survival curves
      were generated to assess prognosis and relapse rate. The initial symptoms and
      disease duration for each patient were recorded. Correlation analyses were
      performed for the association of various parameters with prognosis. Functional
      outcomes were evaluated using the Musculoskeletal Tumor Society (MSTS) guidelines
      after 6 months postoperatively, to analyze the relation between bone excision
      size and function recovery. RESULTS: The resection lengths measured
      intraoperatively ranged from 80 to 230 mm, and contained 3 cm of normal bone
      around the tumor. A total of 3 courses of preoperative chemotherapy were
      administered to all cases. At final follow-up, 1 case showed recurrence.
      Meanwhile, 8 patients (11.6%) died from lung metastasis. Post-operative infection
      occurred in 3 patients; 1 case was maintained with revision surgery. Two cases
      underwent amputation. The mean MSTS system score was 21.6. CONCLUSIONS: The
      multidisciplinary treatment result in an overall positive outcome, with improved
      function.

PMID- 30185177
TI  - A qualitative assessment of the smoking policies and cessation activities at
      smaller workplaces.
AB  - BACKGROUND: To reduce the negative consequences of smoking, workplaces have
      adopted and implemented anti-smoking initiatives. Compared to large workplaces,
      less research exists about these initiatives at smaller workplaces, which are
      more likely to hire low-wage workers with higher rates of smoking. The purpose of
      this study was to describe and compare the smoking policies and smoking cessation
      activities at small (20-99 employees) and very small (< 20 employees) workplaces.
      METHODS: Thirty-two key informants coming from small and very small workplaces in
      Iowa completed qualitative telephone interviews. Data collection occurred between
      October 2016 and February 2017. Participants gave descriptions of the anti
      smoking initiatives at their workplace. Additional interview topics included
      questions on enforcement, reasons for adoption, and barriers and facilitators to
      adoption and implementation. The data were analyzed using counts and content and
      thematic analysis. RESULTS: Workplace smoking policies were nearly universal (n =
      31, 97%), and most workplaces (n = 21, 66%) offered activities to help employees
      quit smoking. Reasons for adoption included the Iowa Smokefree Air Act, to
      improve employee health, and organizational benefits (e.g., reduced insurance
      costs). Few challenges existed to adoption and implementation. Commonly cited
      facilitators included the Iowa Smokefree Air Act, no issues with compliance, and
      support from others. Compared to small workplaces, very small workplaces offered
      cessation activities less often and had fewer tobacco policy restrictions.
      CONCLUSIONS: This study showed well-established tobacco control efforts in small
      workplaces, but very small workplaces lagged behind. To reduce potential health
      disparities in smoking, future research and intervention efforts in tobacco
      control should focus on very small workplaces.

PMID- 30185178
TI  - Activation of the JAK/STAT3 and PI3K/AKT pathways are crucial for IL-6 trans
      signaling-mediated pro-inflammatory response in human vascular endothelial cells.
AB  - BACKGROUND: IL-6 classic signaling is linked to anti-inflammatory functions while
      the trans-signaling is associated with pro-inflammatory responses. Classic
      signaling is induced via membrane-bound IL-6 receptor (IL-6R) whereas trans
      signaling requires prior binding of IL-6 to the soluble IL-6R. In both cases,
      association with the signal transducing gp130 receptor is compulsory. However,
      differences in the downstream signaling mechanisms of IL-6 classic- versus trans
      signaling remains largely elusive. METHODS: In this study, we used flow
      cytometry, quantitative PCR, ELISA and immuno-blotting techniques to investigate
      IL-6 classic and trans-signaling mechanisms in Human Umbilical Vein Endothelial
      Cells (HUVECs). RESULTS: We show that both IL-6R and gp130 are expressed on the
      surface of human vascular endothelial cells, and that the expression is affected
      by pro-inflammatory stimuli. In contrast to IL-6 classic signaling, IL-6 trans
      signaling induces the release of the pro-inflammatory chemokine Monocyte
      Chemoattractant Protein-1 (MCP-1) from human vascular endothelial cells. In
      addition, we reveal that the classic signaling induces activation of the
      JAK/STAT3 pathway while trans-signaling also activates the PI3K/AKT and the
      MEK/ERK pathways. Furthermore, we demonstrate that MCP-1 induction by IL-6 trans
      signaling requires simultaneous activation of the JAK/STAT3 and PI3K/AKT
      pathways. CONCLUSIONS: Collectively, our study reports molecular differences in
      IL-6 classic- and trans-signaling in human vascular endothelial cells; and
      elucidates the pathways which mediate MCP-1 induction by IL-6 trans-signaling.

PMID- 30185179
TI  - High and growing disapproval of sex-selection technology in Australia.
AB  - BACKGROUND: In Australia, the National Health and Medical Research Council has
      banned the use of assisted reproductive technology for social sex selection, but
      notes "there is limited research into the question of whether Australians support
      the use of sex selection for non-medical purposes". This paper investigates
      Australian attitudes to sex-selection technology by different means (IVF,
      abortion, and a hypothetical pill), for different reasons (medical, family
      balancing, any reason), and by differing respondent characteristics (age, sex,
      education and religiosity). METHODS: In 2007 and 2016, the Australian Survey of
      Social Attitudes (AuSSA) collected data on the attitudes of Australian adults to
      sex selection through IVF, abortion, and a hypothetical pill. We calculate
      population-weighted distributions and 95% confidence intervals of responses, and
      carry out logistic regressions to investigate the demographic characteristics of
      Australians who strongly disapprove of IVF or abortion for sex selection.
      RESULTS: In 2016, around three-quarters of AuSSA respondents were opposed to
      legalising sex selection through IVF for any reason, or for family balancing for
      a second or third child. Thirty-seven per cent were opposed to IVF for medical
      sex selection. Two-thirds of respondents in both 2007 and 2016 disapproved or
      strongly disapproved of IVF for sex selection, while the proportion who strongly
      disapproved increased from 31 to 40%. Disapproval/strong disapproval of abortion
      for sex selection increased from 74 to 81% from 2007 to 2016, while strong
      disapproval alone rose from 44 to 55%. More than 70% of respondents in both 2007
      and 2016 stated that a hypothetical pill for sex selection should not be legal.
      Our analysis finds that female, young, more-educated, and more religious
      respondents are more likely to strongly disapprove of sex selection via IVF or
      abortion, and that the increase in those who strongly disapprove from 2007 to
      2016 is statistically significant. CONCLUSIONS: Australians generally disapprove
      of the use of sex-selection technology. If legislation is to be guided by
      community attitudes, then the prohibition against sex selection for non-medical
      purposes through assisted reproductive technology should be maintained.

PMID- 30185180
TI  - Cardiovascular risk profile of patients with atherogenic dyslipidemia in middle
      age Lithuanian population.
AB  - BACKGROUND: Atherogenic dyslipidemia (AD) is a blood serum lipid profile
      abnormality characterized by elevation of triglycerides and reduced levels of
      high density lipoprotein cholesterol (HDL-C). It is associated with residual
      cardiovascular risk. This study evaluated and compared the risk profiles of
      patients with hypertriglyceridemia, low-HDL-C levels or AD, in order to
      understand, which lipid profile is associated with greater risk. METHODS: During
      the period of 2009-2016 a population of 92,373 Lithuanian adults (men 40-54 years
      old and women 50-64 years old) without overt cardiovascular disease were
      analyzed. Data of 25,746 patients (68.6% women and 31.4% men) with
      hypertriglyceridemia and/or low HDL-C low levels were collected and used for
      further statistical analysis. RESULTS: Participants with AD tend to have more
      unfavorable risk profile than participants with hypertriglyceridemia or low-HDL
      C. AD tends to cluster with other atherogenic risk factors, such as arterial
      hypertension [odds ratio (OR) 1.96, 95% confidence intervals (CI) 1.87-2.01],
      smoking [OR 1.20, 95% CI 1.14-1.27], diabetes mellitus [OR 2.74, 95% CI 2.58
      2.90], obesity [OR 2.92, 95% CI 2.78-3.10], metabolic syndrome [OR 22.27, 95% CI
      20.69-23.97], unbalanced diet [OR 1,59, 95% CI 1.51-1.68], low physical activity
      [OR 1.80, 95% CI 1.71-1,89], CHD history in first degree relatives [OR 1.18, 95%
      CI 1.12-1.25] and total number of risk factors [OR 1.47, 95% CI 1.38-1.57].
      CONCLUSION: AD is associated with more unfavorable cardiovascular risk profile
      than hypertriglyceridemia or low-HDL cholesterol levels. Once identified AD
      should require additional medical attention since it is an important factor of
      residual cardiovascular risk.

PMID- 30185181
TI  - The distribution of benefits under China's new rural cooperative medical system:
      evidence from western rural China.
AB  - BACKGROUND: China's New Cooperative Medical Scheme (NCMS) enables insured
      citizens to enjoy the same benefit package by paying a flat-rate premium.
      However, it still remains uncertain whether economically disadvantaged enrollees
      receive insurance benefits that at least match those of non-disadvantaged
      enrollees. This article, therefore, estimates the distribution of benefits under
      the NCMS across economic groups and compares the magnitude of economic-related
      inequity changes in the NCMS benefits. METHODS: Data were drawn from two-wave
      large-scale representative and comparable cross-sectional household health survey
      datasets conducted in Shaanxi Province in 2008 and 2013. In total, 9506 (2008)
      and 38,010 (2013) NCMS enrollees were included. The benefits from the NCMS are
      measured in two ways: via the probability of receiving reimbursements and via the
      absolute amount of the obtained reimbursements. Two-part models were used to
      estimate the benefit distribution and to adjust benefits for health care needs.
      Concentration curve, dominance test of the concentration curve, and concentration
      index (CI) were used to estimate the overall degree of economic-related
      inequality. The degree of horizontal inequity was estimated via indirectly
      standardized measures based on the "equal treatment for equal needs" concept.
      RESULTS: Our results indicate that economically affluent groups were more likely
      to receive reimbursements from the NCMS, and these reimbursements were also
      higher. Positive need-adjusted CIs for the probability of receiving
      reimbursements (CIs: 0.2027/0.1056 in 2008/2013) and the absolute amount of
      reimbursements (CIs: 0.3002/0.1660 in 2008/2013) further suggest the existence of
      clear pro-rich horizontal inequities in the benefits distribution under the NCMS.
      Encouragingly, a decreasing trend could be observed from 2008 to 2013, which
      suggests that horizontal inequities in NCMS benefits that favored the rich
      decreased over the investigated period, while the level of insurance benefits
      improved. CONCLUSIONS: Our study suggests that the benefits of NCMS are
      concentrated toward economically affluent groups. Although any trade-off between
      policy feasibility and equity has become a challenge for the formulation of
      social health insurance funding and benefit packages in developing countries,
      inequality can be gradually reduced through continuous adjustment of the medical
      insurance scheme, thus effectively targeting economically disadvantaged
      enrollees.

PMID- 30185182
TI  - Patterns of conventional and complementary non-pharmacological health practice
      use by US military veterans: a cross-sectional latent class analysis.
AB  - BACKGROUND: Non-pharmacological therapies and practices are commonly used for
      both health maintenance and management of chronic disease. Patterns and reasons
      for use of health practices may identify clinically meaningful subgroups of
      users. The objectives of this study were to identify classes of self-reported use
      of conventional and complementary non-pharmacological health practices using
      latent class analysis and estimate associations of participant characteristics
      with class membership. METHODS: A mailed survey (October 2015 to September 2016)
      of Minnesota National Guard Veterans from a longitudinal cohort (n = 1850)
      assessed current pain, self-reported overall health, mental health, substance
      use, personality traits, and health practice use. We developed the Health
      Practices Inventory, a self-report instrument assessing use of 19 common
      conventional and complementary non-pharmacological health-related practices.
      Latent class analysis was used to identify subgroups of health practice users,
      based on responses to the HPI. Participants were assigned to their maximum
      likelihood class, which was used as the outcome in multinomial logistic
      regression to examine associations of participant characteristics with latent
      class membership. RESULTS: Half of the sample used non-pharmacological health
      practices. Six classes of users were identified. "Low use" (50%) had low rates of
      health practice use. "Exercise" (23%) had high exercise use. "Psychotherapy" (6%)
      had high use of psychotherapy and support groups. "Manual therapies" (12%) had
      high use of chiropractic, physical therapy, and massage. "Mindfulness" (5%) had
      high use of mindfulness and relaxation practice. "Multimodal" (4%) had high use
      of most practices. Use of manual therapies (chiropractic, acupuncture, physical
      therapy, massage) was associated with chronic pain and female sex.
      Characteristics that predict use patterns varied by class. Use of self-directed
      practices (e.g., aerobic exercise, yoga) was associated with the personality
      trait of absorption (openness to experience). Use of psychotherapy was associated
      with higher rates of psychological distress. CONCLUSIONS: These observed patterns
      of use of non-pharmacological health practices show that functionally similar
      practices are being used together and suggest a meaningful classification of
      health practices based on self-directed/active and practitioner-delivered.
      Notably, there is considerable overlap in users of complementary and conventional
      practices.

PMID- 30185184
TI  - Calcification of the intervertebral disc and ossification of posterior
      longitudinal ligament in children.
AB  - BACKGROUND: IDC in children, first reported by Baron in 1924, is very rare. OPLL
      of the cervical spine mainly affect people ages 50-70 years. The coexistence of
      IDC and OPLL in children is very rare, only six cases with 3 to 24 months' follow
      up were reported to date. CASE PRESENTATION: A 6-year-old boy presented with
      complains of neck pain at July 2007. The boy was treated by conservative
      treatment and observed up for 9 years. Neck pain greatly improved after a one
      month conservative treatment and never recur. Laboratory tests revealed elevated
      ESR and CRP at admission and found nothing abnormal at 19-month and 9-year follow
      up. Computed tomography and magnetic resonance imaging revealed IDC at C2/3, C3/4
      and OPLL at C3/4 at admission and found minor calcification at C2/3 remained but
      calcification at C3/4 and OPLL at C3/4 completely disappeared at 19-month and 9
      year follow-up. Nineteen months after initial diagnosis, restoration of T2
      weighted signal intensity of C2/3 and C3/4 discs was observed through MRI. Loss
      of T2-weighted signal intensity of C2/3 disc and decrease of T2-weighted signal
      intensity of C3/4 disc was observed at 9-year follow-up. CONCLUSIONS: IDC with
      OPLL in children is very rare. Conservative treatments are recommended with
      affirmative short-term and long-term clinical effects. More intensive observation
      with long-term follow-ups may be needed to warrant the clinical effects.

PMID- 30185185
TI  - Cohort identification of axial spondyloarthritis in a large healthcare dataset:
      current and future methods.
AB  - BACKGROUND: Big data research is important for studying uncommon diseases in real
      world settings. Most big data studies in axial spondyloarthritis (axSpA) have
      been limited to populations identified with billing codes for ankylosing
      spondylitis (AS). axSpA is a more inclusive concept, and reliance on AS codes
      does not produce a comprehensive axSpA study population. The first objective was
      to describe our process for establishing an appropriate sample of patients with
      and without axSpA for developing accurate axSpA identification methods. The
      second objective was to determine the classification performance of AS billing
      codes against the chart-reviewed axSpA reference standard. METHODS: Veteran
      Health Affairs clinical and administrative data, between January 2005 and June
      2015, were used to randomly select patients with clinical phenotypes that
      represented high, moderate, and low likelihoods of an axSpA diagnosis. With chart
      review, the sampled patients were classified as Yes axSpA, No axSpA or Uncertain
      axSpA, and these classification assignments were used as the reference standard
      for determining the positive predictive value (PPV) and sensitivity of AS ICD-9
      codes for axSpA. RESULTS: Six hundred patients were classified as Yes axSpA
      (26.8%), No axSpA (68.3%), or Uncertain axSpA (4.8%). The PPV and sensitivity of
      an AS ICD-9 code for axSpA were 83.3% and 57.3%, respectively. CONCLUSIONS:
      Standard methods of identifying axSpA patients in a large dataset lacked
      sensitivity. An appropriate sample of patients with and without axSpA was
      established and characterized for developing novel axSpA identification methods
      that are anticipated to enable previously impractical big data research.

PMID- 30185183
TI  - Development of broadly neutralizing antibodies in HIV-1 infected elite
      neutralizers.
AB  - Broadly neutralizing antibodies (bNAbs), able to prevent viral entry by diverse
      global viruses, are a major focus of HIV vaccine design, with data from animal
      studies confirming their ability to prevent HIV infection. However, traditional
      vaccine approaches have failed to elicit these types of antibodies. During
      chronic HIV infection, a subset of individuals develops bNAbs, some of which are
      extremely broad and potent. This review describes the immunological and
      virological factors leading to the development of bNAbs in such "elite
      neutralizers". The features, targets and developmental pathways of bNAbs from
      their precursors have been defined through extraordinarily detailed within-donor
      studies. These have enabled the identification of epitope-specific commonalities
      in bNAb precursors, their intermediates and Env escape patterns, providing a
      template for vaccine discovery. The unusual features of bNAbs, such as high
      levels of somatic hypermutation, and precursors with unusually short or long
      antigen-binding loops, present significant challenges in vaccine design. However,
      the use of new technologies has led to the isolation of more than 200 bNAbs,
      including some with genetic profiles more representative of the normal
      immunoglobulin repertoire, suggesting alternate and shorter pathways to breadth.
      The insights from these studies have been harnessed for the development of
      optimized immunogens, novel vaccine regimens and improved delivery schedules,
      which are providing encouraging data that an HIV vaccine may soon be a realistic
      possibility.

PMID- 30185186
TI  - The private healthcare market and the sustainability of an innovative community
      nurses programme based on social entrepreneurship - CoNSENSo project.
AB  - BACKGROUND: CoNSENSo is a project funded by the European Union, which is aimed at
      developing an innovative care model based on community nurses to support active
      ageing in mountain areas. The planned sustainability of this innovative approach
      relies on social entrepreneurship on the healthcare market, and this work
      highlights the necessary conditions for the successful implementation of these
      entrepreneurial initiatives. METHODS: Considering municipalities in the Piedmont
      Region and those aged 65 or older as target population, the authors propose
      several negative binomial regression models to estimate the effectiveness of
      current private healthcare services in supporting the active aging process. Such
      effectiveness may represent the ex-ante (positive) reputation of these new social
      entrepreneurial initiatives on the market. RESULTS: According to our results, the
      private supply of healthcare services can effectively support the aging process.
      Indeed, given that the other predictor variables in the model are held constant,
      there are statistically significant negative relations between the number of hip
      fractures and the private supply of healthcare services by dental practitioners
      and psychologists (p-value < 0.05), as well as the private supply of
      opportunities for social interaction by coffee bars (p-value < 0.05).
      CONCLUSIONS: The authors expect a favourable environment for the entrepreneurial
      initiatives of community nurses in mountain areas. Accordingly, policy makers
      cannot reject the hypothesis that the goals reached by the CoNSENSo project may
      be maintained for the sake of the future generations, avoiding its collapse as
      soon as public funding shifts to new programmes.

PMID- 30185187
TI  - Ethnobotanical survey of plant species for herbal tea in a Yao autonomous county
      (Jianghua, China): results of a 2-year study of traditional medicinal markets on
      the Dragon Boat Festival.
AB  - BACKGROUND: Herbal tea is widely consumed in Jianghua, a Yao autonomous county in
      Hunan Province, China, to prevent and treat diseases. The materials in herbal tea
      at the traditional medicinal markets at the Dragon Boat Festival remain unknown.
      The aims of the paper were (1) to specifically investigate the materials of
      herbal tea used by Yao nationalities in Hunan Province, (2) to record the most
      common and the culturally important medicinal plant species in the markets, and
      (3) to compare the medical plant tradition both used for herbal tea between the
      Jianghua and Lingnan regions. METHODS: During 2016-2017, 215 vendors were
      interviewed at traditional medicinal markets at the Dragon Boat Festival in
      Jianghua to record plants used for herbal tea and to document traditional
      knowledge of their medicinal function, habitat, and conservation status. Bunches
      of medicinal plants were purchased to identify the species and to prepare voucher
      specimens. Cognitive salience (CS) based on free-lists and use value (UV) were
      calculated to analyze the cultural importance of medical plants; other
      quantitative methods (coefficient of similarity and chi-square analysis) were
      applied for comparison of herbal tea tradition between the Jianghua and Lingnan
      regions. RESULTS: A total of 169 species belonging to 66 families and 142 genera
      were recorded in herbal tea to treat health conditions in the study area. There
      were 30 health conditions that were recorded, with heat-clearing and detoxifying
      being the most common medicinal function, followed by treating rheumatism and
      promoting blood circulation. Of the 169 species, 97 were herbs. The whole plant
      was the most commonly used plant part in the preparation of herbal tea. According
      to the national evaluation criteria, three of these species are listed on
      "China's red list" and registered as vulnerable (VU). By comparing the
      coefficient of similarity of herbal tea plants and the number of mentions for
      part(s) used in Jianghua and Lingnan, the medicinal plant tradition is different
      in two areas. CONCLUSIONS: Herbal tea in Jianghua reflects the cultural diversity
      of the Yao people and the plant diversity of the region. Future research on the
      safety, efficacy, and the adulterants of herbal tea are needed for sustainable
      utilization.

PMID- 30185188
TI  - Elucidating redox balance shift in Scheffersomyces stipitis' fermentative
      metabolism using a modified genome-scale metabolic model.
AB  - BACKGROUND: Scheffersomyces stipitis is an important yeast species in the field
      of biorenewables due to its desired capacity for xylose utilization. It has been
      recognized that redox balance plays a critical role in S. stipitis due to the
      different cofactor preferences in xylose assimilation pathway. However, there has
      not been any systems level understanding on how the shift in redox balance
      contributes to the overall metabolic shift in S. stipitis to cope with reduced
      oxygen uptake. Genome-scale metabolic network models (GEMs) offer the opportunity
      to gain such systems level understanding; however, currently the two published
      GEMs for S. stipitis cannot be used for this purpose, as neither of them is able
      to capture the strain's fermentative metabolism reasonably well due to their poor
      prediction of xylitol production, a key by-product under oxygen limited
      conditions. RESULTS: A system identification-based (SID-based) framework that we
      previously developed for GEM validation is expanded and applied to refine a
      published GEM for S. stipitis, iBB814. After the modified GEM, named iDH814, was
      validated using literature data, it is used to obtain genome-scale understanding
      on how redox cofactor shifts when cells respond to reduced oxygen supply. The SID
      based framework for GEM analysis was applied to examine how the environmental
      perturbation (i.e., reduced oxygen supply) propagates through the metabolic
      network, and key reactions that contribute to the shifts of redox and metabolic
      state were identified. Finally, the findings obtained through GEM analysis were
      validated using transcriptomic data. CONCLUSIONS: iDH814, the modified model, was
      shown to offer significantly improved performance in terms of matching available
      experimental results and better capturing available knowledge on the organism.
      More importantly, our analysis based on iDH814 provides the first genome-scale
      understanding on how redox balance in S. stipitis was shifted as a result of
      reduced oxygen supply. The systems level analysis identified the key contributors
      to the overall metabolic state shift, which were validated using transcriptomic
      data. The analysis confirmed that S. stipitis uses a concerted approach to cope
      with the stress associated with reduced oxygen supply, and the shift of reducing
      power from NADPH to NADH seems to be the center theme that directs the overall
      shift in metabolic states.

PMID- 30185189
TI  - A comparison of brain magnetic resonance imaging lesions in multiple sclerosis by
      race with reference to disability progression.
AB  - BACKGROUND: We compared the magnetic resonance imaging (MRI) features between
      Japanese and Caucasian patients with multiple sclerosis (MS), and identified the
      relationships between MRI features and disability. METHODS: From the baseline
      data of phase II fingolimod trials, 95 Japanese and 246 Caucasian relapsing
      remitting MS patients were enrolled. The number, volume, and distribution of
      brain MRI lesions were evaluated using T2-weighted (T2W) images. Cross-sectional
      total normalized brain volume (NBV), normalized cortical gray matter volume,
      normalized deep gray matter volume (NDGMV), normalized white matter volume
      (NWMV), and normalized thalamic volume were measured. RESULTS: Japanese patients
      had significantly lower Expanded Disability Status Scale (EDSS) scores than
      Caucasian patients (mean 2.0 vs. 2.3, p = 0.008), despite a similar disease
      duration. Japanese patients showed a trend towards fewer T2W-lesions (median 50
      vs. 65, p = 0.08) and significantly lower frequencies of cerebellar and parietal
      lobe lesions (p = 0.02 for both) than Caucasian patients. There were no
      differences in T2W-lesion volume between races, whereas Japanese patients had a
      significantly larger T2W-lesion volume per lesion compared with Caucasian
      patients (median 140 mm3 vs. 85 mm3, p < 0.0001). T2W-lesion volumes were
      positively correlated with EDSS scores in Japanese patients (p < 0.0001). In both
      races, NBV, normalized cortical gray matter volume, NDGMV, and thalamic volume
      were negatively correlated with disease duration and EDSS scores (p < 0.01 for
      all). NWMV was negatively correlated with disease duration and EDSS scores only
      in Caucasian patients (p = 0.03 and p = 0.004, respectively). NBV, NDGMV, NWMV,
      and thalamic volume were consistently smaller in Japanese compared with Caucasian
      patients throughout the entire examined disease duration (p = 0.046, p = 0.01, p
      = 0.005, and p = 0.04, respectively). Japanese patients had a significantly
      faster reduction in NDGMV (p = 0.001), particularly for thalamic volume (p =
      0.001), with disease duration compared with Caucasian patients. CONCLUSIONS: Gray
      matter atrophy is a common denominator for disability in Japanese and Caucasian
      patients. Additional contributory factors for disability include T2W-lesion
      volume in Japanese patients and white matter atrophy in Caucasian patients. Less
      frequent parietal and cerebellar involvement with fewer T2W-lesions may underlie
      milder disability in Japanese patients.

PMID- 30185190
TI  - Effect of duration of diabetes on bone mineral density: a population study on
      East Asian males.
AB  - BACKGROUND: The aim of the present study is to evaluate the association between
      BMD and type 2 DM status in middle-aged and elderly men. To investigate a
      possible correlation, the present study used the BMD dataset of the Korea
      National Health and Nutrition Examination Survey (KNHANES) from 2008 to 2011.
      METHODS: In total, 37,753 individuals participated in health examination surveys
      between 2008 and 2011. A total of 3383 males aged >=50 years were eligible. They
      underwent BMD measurement through dual-energy X-ray absorptiometry (DXA). The
      fasting plasma glucose and insulin levels of participants were also measured.
      RESULTS: Men with prediabetes and diabetes had significantly higher mean BMD at
      all measured sites than control men did, irrespective of DM status. This was
      confirmed by multivariable linear regression analyses. DM duration was an
      important factor affecting BMD. Patients with DM for > 5 years had lower mean BMD
      in the total hip and femoral neck than those with DM for <=5 years. Per
      multivariable linear regression analyses, patients with DM for > 5 years had
      significantly lower mean BMD at the femoral neck than those with DM <=5 years.
      CONCLUSIONS: DM duration was significantly associated with reduced femoral neck
      BMD.

PMID- 30185191
TI  - Understanding the persistence of vertical (stand-alone) HIV clinics in the health
      system in Uganda: a qualitative synthesis of patient and provider perspectives.
AB  - BACKGROUND: Although there is mounting evidence and policy guidance urging the
      integration of HIV services into general health systems in countries with a high
      HIV burden, vertical (stand-alone) HIV clinics are still common in Uganda. We
      sought to describe the specific contexts underpinning the endurance of vertical
      HIV clinics in Uganda. METHODS: A qualitative research design was adopted. Semi
      structured interviews were conducted with the heads of HIV clinics, clinicians
      and facility in-charges (n = 78), coupled with eight focus group discussions (64
      participants) with patients from 16 health facilities purposively selected, from
      a nationally-representative sample of 195 health facilities across Uganda,
      because they run stand-alone HIV clinics. Data were analyzed by thematic approach
      as guided by the theory proposed by Shediac-Rizkallah & Bone (1998) which
      identifies; Intervention characteristics, organizational context, and broader
      environment factors as potentially influential on health programme
      sustainability. RESULTS: Intervention characteristics: Provider stigma was
      reported to have been widespread in the integrated care experience of
      participating health facilities which necessitated the establishment of stand
      alone HIV clinics. HIV disease management was described as highly specialized
      which necessitated a dedicated workforce and vertical HIV infrastructure such as
      counselling rooms. Organizational context: Participating health facilities
      reported health-system capacity constraints in implementing integrated systems of
      care due to a shortage of ART-proficient personnel and physical space, a lack of
      laboratory capacity to concurrently conduct HIV and non-HIV tests and increased
      workloads associated with implementing integrated care. Broader environment
      factors: Escalating HIV client loads and external HIV funding architectures were
      perceived to have perpetuated verticalized HIV programming over the past decade.
      CONCLUSION: Our study offers in-depth, contextualized insights into the factors
      contributing to the endurance of vertical HIV clinics in Uganda. Our analysis
      suggests that there is a complex interaction in supply-side constraints (shortage
      of ART-proficient personnel, increased workloads, laboratory capacity
      deficiencies) and demand-side factors (escalating demand for HIV services,
      psychosocial barriers to HIV care) as well as the specialized nature of HIV
      disease management which pose challenges to the integrated-health services
      agenda.

PMID- 30185193
TI  - Quality of life in older adults following a hip fracture: an empirical comparison
      of the ICECAP-O and the EQ-5D-3 L instruments.
AB  - BACKGROUND: The purpose of this study was to empirically compare the performance
      of two generic preference based quality of life instruments, EQ-5D-3 L (with a
      health and physical function focus) and ICECAP-O (with a wellbeing and capability
      focus), in a population of older Australians following hip fracture. METHODS:
      Older adults or their family member proxies (in cases of severe cognitive
      impairment) following surgery to repair a fractured hip were invited to take part
      in this cross sectional study. Inclusion criteria included an age of 60 years or
      older, confirmed falls-related hip fracture and those receiving current
      palliative care or consented to other research studies were excluded. 87
      participants completed the ICECAP-O and EQ-5D-3 L instruments between one and
      three weeks post-surgery. RESULTS: For the hip fracture population, the mean
      ICECAP-O score was 0.639 (SD 0.206, n = 82) and the mean EQ-5D-3 L utility score
      was 0.545 (SD 0.251, n = 87). There was a statistically significant positive
      correlation between the ICECAP-O and EQ-5D-3 L scores (r = 0.529, p = < 0.001).
      CONCLUSIONS: Study findings indicate significant impairments in quality of life
      post hip fracture. In multiple regression analyses, age and health-related QoL
      (measured by the EQ-5D) were significant determinants of ICECAP-O scores, while
      proxy respondent status, age, and capability-related QoL (measured by the ICECAP
      O) were significant determinants of EQ-5D scores. Approaches to measuring and
      valuing quality of life in this sample, should consider the target domains of the
      intervention in their choice of instrument. Studies aiming to measure the impact
      of interventions targeting broader domains of wellbeing and QoL should consider
      including a broader measure of QoL in conjunction with a HRQoL measure.

PMID- 30185192
TI  - Adaptive School-based Implementation of CBT (ASIC): clustered-SMART for building
      an optimized adaptive implementation intervention to improve uptake of mental
      health interventions in schools.
AB  - BACKGROUND: Depressive and anxiety disorders affect 20-30% of school-age youth,
      most of whom do not receive adequate services, contributing to poor developmental
      and academic outcomes. Evidence-based practices (EBPs) such as cognitive
      behavioral therapy (CBT) can improve outcomes, but numerous barriers limit access
      among affected youth. Many youth try to access mental health services in schools,
      but school professionals (SPs: counselors, psychologists, social workers) are
      rarely trained adequately in CBT methods. Further, SPs face organizational
      barriers to providing CBT, such as lack of administrative support. Three
      promising implementation strategies to address barriers to school-based CBT
      delivery include (1) Replicating Effective Programs (REP), which deploys
      customized CBT packaging, didactic training in CBT, and technical assistance; (2)
      coaching, which extends training via live supervision to improve SP competence in
      CBT delivery; and (3) facilitation, which employs an organizational expert who
      mentors SPs in strategic thinking to promote self-efficacy in garnering
      administrative support. REP is a relatively low-intensity/low-cost strategy,
      whereas coaching and facilitation require additional resources. However, not all
      schools will require all three strategies. The primary aim of this study is to
      compare the effectiveness of a school-level adaptive implementation intervention
      involving REP, coaching, and facilitation versus REP alone on the frequency of
      CBT delivered to students by SPs and student mental health outcomes. Secondary
      and exploratory aims examine cost-effectiveness, moderators, and mechanisms of
      implementation strategies. METHODS: Using a clustered, sequential multiple
      assignment, randomized trial (SMART) design, >= 200 SPs from 100 schools across
      Michigan will be randomized initially to receive REP vs. REP+coaching. After 8
      weeks, schools that do not meet a pre-specified implementation benchmark are re
      randomized to continue with the initial strategy or to augment with facilitation.
      DISCUSSION: EBPs need to be implemented successfully and efficiently in settings
      where individuals are most likely to seek care in order to gain large-scale
      impact on public health. Adaptive implementation interventions hold the promise
      of providing cost-effective implementation support. This is the first study to
      test an adaptive implementation of CBT for school-age youth, at a statewide
      level, delivered by school staff, taking an EBP to large populations with limited
      mental health care access. TRIAL REGISTRATION: NCT03541317 -Registered on 29 May
      2018 on ClinicalTrials.gov PRS.

PMID- 30185194
TI  - Psychometric properties the Iranian version of Older People's Quality Of Life
      questionnaire (OPQOL).
AB  - BACKGROUND: Assessing quality of life (QOL) in elderly needs specific
      instruments. The Older People's Quality of Life Questionnaire (OPQOL-35) is one
      of the common tools that used for measuring quality of life in elderly
      populations. The questionnaires contains 35 items tapping into eight domains
      including life overall, health, social relationships and participation,
      independence, control over life and freedom, home and neighborhood, psychological
      and emotional well-being, financial circumstances, culture and religion. This
      study aimed to translate and validate the OPQOL-35 in Iran. METHODS: Forward
      backward procedure was applied to translate the original questionnaire from
      English into Persian. Then following qualitative face and content validity, a
      sample of elderly people completed the questionnaire. In order to evaluate the
      construct validity, exploratory and confirmatory factor analyses was performed.
      Subsequently, convergent and divergent validity of the factors were evaluated.
      Reliability was evaluated by performing internal consistency analysis and
      Intraclass Correlation Coefficients (ICC). RESULTS: In all 500 older people
      completed the questionnaire. The mean age of participant was 68.92 (SD = 6.97)
      years, and mostly were males (66.6%). The result of exploratory factor analysis
      showed 8 factors with Eigen values of greater than one, which explained 67.4% of
      the variance observed. Confirmatory factor analysis showed acceptable fit indexes
      for the data [Comparative Fit Index (CFI) = 0.92, Minimum Discrepancy Function by
      Degrees of Freedom divided (CMIN/DF) = 2.832, Root Mean Square Error of
      Approximation (RMSEA) = 0.067]. The convergent and divergent validity did not
      support three latent factors (Life overall, Independence, control over life,
      freedom and Psychological and emotional well-being). Convergent and divergent
      validity shown that construct fulfilled for the health, social relationships and
      participation, home and neighborhood, financial circumstances, culture and
      religion latent factors, however the results did not support the convergent and
      divergent validity for three latent factors (Life overall, Independence, control
      over life, freedom and Psychological and emotional well-being). Cronbach's alpha
      coefficient for the subscales ranged from 0.65-0.95. Test-retest reliability
      (ICC) of the questionnaire with two weeks interval were ranged from 0.88-0.95
      indicating a good range of reliability. CONCLUSION: The findings suggest that the
      Iranian version of OPQOL-35 is a valid measure for assessing quality of life in
      elderly populations in different settings.

PMID- 30185195
TI  - Primary histiocytic sarcoma of the central nervous system: a case report with
      platelet derived growth factor receptor mutation and PD-L1/PD-L2 expression and
      literature review.
AB  - BACKGROUND: Histiocytic sarcoma (HS) is an aggressive malignant neoplasm. HS in
      the central nervous system is exceptionally rare and associated with a poor
      prognosis. This report documents a case of primary HS of the central nervous
      system with treatment including surgery, radiotherapy, and chemotherapy. CASE
      PRESENTATION: Our patient was a 47 year old female presenting with progressive
      ataxia, headaches, imbalance, nausea, vomiting, and diplopia. MRI showed a
      heterogeneously enhancing lesion approximately 2.9 * 3.0 * 2.3 cm centered upon
      the cerebellar vermis with mild surrounding vasogenic edema and abnormal
      enhancement of multiple cranial nerves. The patient underwent surgical debulking,
      which revealed histiocytic sarcoma with grossly purulent drainage. Staging
      revealed diffuse leptomeningeal involvement, primarily involving the brain and
      lower thoracic and lumbar spine. She underwent adjuvant radiotherapy to the brain
      and lower spine and was started on high dose methotrexate. However, she
      experienced progressive disease in the cervical and thoracic spine as well as
      pulmonary involvement. Genomic sequencing of her tumor showed a mutation in the
      platelet-derived growth factor receptor A (p.V0681) which could be targeted with
      Dasatinib. However, she did not tolerate Dasatinib and she succumbed to
      progressive disseminated disease eight months from original diagnosis. Our
      pathologic evaluation also revealed expression of PD-L1 and PD-L2 by tumor cells
      raising the potential therapeutic role for immune checkpoint inhibition.
      CONCLUSIONS: This case provides an example of effective CNS control with
      resection and moderate doses of radiation therapy. A review of the literature
      confirms aggressive multidisciplinary treatment is the most effective treatment
      against this disease. In addition, genomic sequencing may play an important role
      in determining new therapeutic options. However, CNS histiocytic sarcoma remains
      an aggressive disease with a propensity for early widespread dissemination and
      few long term survivors.

PMID- 30185196
TI  - Lantern-shaped screw loaded with autologous bone for treating osteonecrosis of
      the femoral head.
AB  - BACKGROUND: Treatment for osteonecrosis of the femoral head (ONFH) in young
      individuals remains controversial. We developed a lantern-shaped screw, which was
      designed to provide mechanical support for the femoral head to prevent its
      collapse, for the treatment of ONFH. The purpose of this study was to investigate
      the efficacy and safety of the lantern-shaped screw loaded with autologous bone
      for the treatment of pre-collapse stages of ONFH. METHODS: Thirty-two patients
      were randomly divided into two groups: the lantern-shaped screw group (core
      decompression and lantern-shaped screw loaded with autogenous bone) and the
      control group (core decompression and autogenous bone graft). During 36 months
      follow-up after surgery, treatment results in patients were assessed by X-ray and
      computed tomography (CT) scanning as well as functional recovery Harris hip score
      (HHS). RESULTS: Successful clinical results were achieved in 15 of 16 hips (94%)
      in the lantern-shaped screw group compared with 10 of 16 hips (63%) in the
      control group (p = 0.0325). Successful radiological results were achieved in 14
      of 16 hips (88%) in the lantern-shaped screw group compared with 8 of 16 hips
      (50%) in the control group (P = 0.0221). CONCLUSION: The lantern-shaped screw
      loaded with autologous bone for the treatment of pre-collapse stages of ONFH is
      effective and results in preventing progression of ONFH and reducing the risk of
      femoral head collapse. TRIAL REGISTRATION: The trial registration number: ChiCTR
      TRC-13004078 (retrospectively registered at 2013-11-28).

PMID- 30185197
TI  - Effectiveness of educational outreach visits compared with usual guideline
      dissemination to improve family physician prescribing-an 18-month open cluster
      randomized trial.
AB  - BACKGROUND: Educational outreach visits are meant to improve the practice of
      health professionals by promoting face-to-face visits to deliver educational
      contents. They have been shown to change prescription behavior, but long-term
      effects are still uncertain. This trial aimed to determine if they improve family
      physician prescribing compared with passive guideline dissemination. METHODS:
      Parallel, open, superiority, and cluster-randomized trial. National Health
      Service primary care practices (clusters) were recruited in the Lisbon region
      Portugal between March 2013 and January 2014. They could enter if they had at
      least four family physicians willing to participate and not planning to retire in
      the follow-up period. Three national guidelines were chosen for dissemination:
      acid secretion modifiers, non-steroidal anti-inflammatory drugs, and
      antiplatelets. Physicians in the intervention group received one 15 to 20 min
      educational outreach visit at their workplace for each guideline. Physicians in
      the control group had access to guidelines through the Directorate-General for
      Health's website (passive dissemination). Primary outcomes were the proportion of
      COX-2 inhibitors prescribed within the NSAID class and the proportion of
      omeprazole within the PPI class at 18 months after the intervention. A cost
      benefit analysis was performed. Practices were randomized by minimization. Data
      analyses were done at individual physician level using generalized mixed-effects
      regression models. Participants could not be blinded. RESULTS: Thirty-eight
      practices with 239 physicians were randomized (120 to intervention and 119 to
      control). Of 360 planned visits, 322 were delivered. No differences were found
      between physicians in the intervention and control groups regarding the
      proportion of omeprazole prescribed among PPIs 18 months after the visit (46.28
      vs 47.15%, p = 0.971) or the proportion of COX-2 inhibitors among NSAIDs (12.07
      vs 13.08%, p = 0.085). All secondary outcome comparisons showed no effect. There
      was no difference in cumulative drug costs at 18 months (3223.50?/1000 patients
      in the intervention group and 3143.92?/1000 patients in the control group, p =
      0.848). CONCLUSIONS: Educational outreach visits were unsuccessful in improving
      compliance with guideline recommendations among Portuguese family physicians. No
      effects were observed at 1, 6, and 18 months after the intervention, and there
      were no associated cost savings. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT01984034 . Registered 7 November 2013.

PMID- 30185198
TI  - Association between the sonographer's experience and diagnostic performance of
      IOTA simple rules.
AB  - BACKGROUND: To validate the clinical value of simple rules in distinguishing
      malignant adnexal masses from benign ones and to explore the effect of simple
      rules for experienced and less-experienced sonographers. METHODS: Patients with
      persistent adnexal masses were enrolled between November 2013 and December 2015.
      All masses were proven through histological examinations. Five sets of diagnoses
      were made and compared with one another. Diagnosis 1 was made, according to the
      simple rules, by a trainee with little clinical diagnostic experience. Diagnoses
      2 and 3 were made by experienced and less-experienced sonographers, respectively,
      according to their clinical experiences. With diagnosis 1 as a reference, the two
      sonographers were asked to provide a second diagnosis, which were diagnoses 4 and
      5. The efficiency of the five sets of diagnoses was compared using ROC curves.
      RESULTS: In total, 75 malignant (37.7%) and 124 benign lesions (62.3%) were
      enrolled in this study. The mean diameter of the benign masses was obviously
      smaller than that of the malignant ones (6.8 +/- 3.4 cm vs. 9.3 +/- 4.9 cm, p <
      0.01). The malignant ratio in postmenopausal women was much higher (66.1%) than
      that in the premenopausal population (25.7%) (p < 0.0001). Totally, 156 of the
      199 cases (79.4%) resulted in conclusive diagnoses. Sensitivity and specificity
      were 98.4% and 73.9%, respectively, among the conclusive cases. The area under
      the ROC curve (Az) for the simple rule diagnosis was significantly lower than
      that for the experienced sonographer diagnosis (0.85 vs. 0.96, p < 0.0001);
      compared with the less-experienced sonographer, this difference was not
      significant (0.85 vs. 0.86, p = 0.9776). No significant difference was found in
      the comparison between the diagnoses made by the experienced sonographer before
      and after referencing the simple rule diagnosis (Az, 0.96 vs. 0.97, p = 0.2055).
      Using diagnosis 1 as a reference, the diagnostic performance of the less
      experienced sonographer increased (from 0.86 to 0.92, p = 0.012); however, it was
      still lower than that of the experienced sonographer (Az, 96% vs. 92%, p =
      0.0241). CONCLUSIONS: The simple rules was an appealing method for discriminating
      malignant masses from benign ones, particularly for a less-experienced
      sonographer.

PMID- 30185199
TI  - An evaluation of anesthetic fade in motor evoked potential monitoring in spinal
      deformity surgeries.
AB  - BACKGROUND: Intraoperative neuromonitoring using motor evoked potentials (MEP)
      satisfactorily detects motor tract integrity changes during spinal surgery.
      However, monitoring is affected by "anesthetic fade," in which the stimulation
      threshold increases because the waveform amplitude decreases with the
      accumulation of propofol. Therefore, the purpose of this study was to clarify the
      effect of anesthetic fade on transcranial MEPs by investigating the time
      dependent changes of amplitude during spinal deformity surgeries. METHODS: We
      retrospectively reviewed medical records of 142 spinal deformity patients (66
      patients with idiopathic scoliosis, 28 with adult spinal deformities, 19 with
      neuromuscular scoliosis, 17 with syndromic scoliosis, and 12 with congenital
      scoliosis). The average age was 28 years (range, 5 to 81 years). MEPs were
      recorded bilaterally from the abductor digiti minimi (ADM) and abductor hallucis
      (AH) muscles during spinal deformity surgeries. The Wilcoxon signed-rank test was
      used to investigate the time-dependent changes of amplitude after propofol
      infusion to evaluate anesthetic fade effects. RESULTS: The average time to
      baseline from initial propofol infusion was 113 min (range, 45 to 182 min). In
      the ADM, the amplitude was 52% at 1 h after initial propofol infusion, 102% at 2
      h, 105% at 3 h, 101% at 4 h, 86% at 5 h, and 81% at 6 h. Compared to the 2-h time
      point, MEP decreased significantly by 16% at 5 h (P < 0.0005) and by 21% at 6 h
      (P < 0.05). In the AH, the amplitude was 49% at 1 h after initial infusion of
      propofol, 102% at 2 h, 102% at 3 h, 92% at 4 h, 71% at 5 h, and 63% at 6 h.
      Compared to the 2-h time point, MEP decreased significantly by 10% at 4 h (P <
      0.005), by 31% at 5 h (P < 0.0000005), and by 39% at 6 h (P < 0.05). CONCLUSIONS:
      MEP amplitude significantly decreased in the upper limbs at 5 and 6 h and in the
      lower limbs at 4, 5, and 6 h after the initial infusion of propofol,
      respectively. The influence of anesthetic fade could influence false positive
      MEPs during long spinal surgeries.

PMID- 30185200
TI  - Towards a global monitoring system for implementing the Rio Political Declaration
      on Social Determinants of Health: developing a core set of indicators for
      government action on the social determinants of health to improve health equity.
AB  - BACKGROUND: In the 2011 Rio Political Declaration on Social Determinants of
      Health, World Health Organization (WHO) Member States pledged action in five
      areas crucial for addressing health inequities. Their pledges referred to better
      governance for health and development, greater participation in policymaking and
      implementation, further reorientation of the health sector towards reducing
      health inequities, strengthening of global governance and collaboration, and
      monitoring progress and increasing accountability. WHO is developing a global
      system for monitoring governments' and international organizations' actions on
      the social determinants of health (SDH) to increase transparency and
      accountability, and to guide implementation, in alignment with broader health and
      development policy frameworks, including the universal health coverage and
      Sustainable Development Goals (SDG) agendas. We describe the selection of
      indicators proposed to be part of the initial WHO global system for monitoring
      action on the SDH. METHODS: An interdisciplinary working group was established by
      WHO, the Public Health Agency of Canada, and the Canadian Institutes of Health
      Research-Institute of Population and Public Health. We describe the processes and
      criteria used for selecting SDH action indicators that were of high quality and
      the described the challenges encountered in creating a set of metrics for
      capturing government action on addressing the Rio Political Declaration's five
      Action Areas. RESULTS: We developed 19 measurement concepts, identified and
      screened 20 indicator databases and systems, including the 223 SDG indicators,
      and applied strong criteria for selecting indicators for the core indicator set.
      We identified 36 suitable existing indicators, which were often SDG indicators.
      CONCLUSIONS: Lessons learnt included the importance of ensuring diversity of the
      working group and always focusing on health equity; challenges included the
      relative dearth of data and indicators on some key interventions and capturing
      the context and level of implementation of indicator interventions.

PMID- 30185201
TI  - A new anatomic locking plate for the treatment of posterolateral tibial plateau
      fractures.
AB  - BACKGROUND: Posterolateral tibial plateau fractures have become more common, and
      their treatment is of great importance to knee function. Additionally, there is
      no available literature detailing specialized anatomic locking plate for tibial
      plateau fractures. Therefore, the aim of the study was to evaluate the safety and
      clinical efficacy of an innovative anatomic locking plate for treatment of
      posterolateral tibial plateau fractures. METHODS: Between March 2014 and January
      2016, 12 patients with posterolateral tibial plateau fracture underwent surgery
      with the anatomic locking plate for the posterolateral tibial plateau via the
      posterolateral approach. Relevant operational data for clinical evaluation were
      collected. RESULTS: The mean follow-up time was 26 months, and the mean age was
      35 years for 12 patients. The mean interval between the time of injury and the
      surgery was 6.1 days. Radiological fracture union was evident in all patients at
      12 weeks. During surgery, the blood loss ranged from 100 to 300 mL, and the
      duration ranged from 55 to 90 min. The Tegner-Lysholm functional score ranged
      from 85 to 97 at the final follow-up. Moreover, the final Rasmussen functional
      score ranged from 25 to 29, and Rasmussen anatomical score ranged from 13 to 18.
      CONCLUSIONS: The newly designed anatomic locking plate for the posterolateral
      tibial plateau provided adequate fixation along the posterolateral tibial
      plateau. It proved to be safe and effective in a small-sample-size population (12
      patients) during a 12- to 34-month follow-up.

PMID- 30185202
TI  - Efficacy of K-wire tension band fixation compared with other alternatives for
      patella fractures: a meta-analysis.
AB  - BACKGROUND: To compare the efficacy and safety of K-wire tension band fixation
      (KTB) with other alternative approaches (cannulated screws, cable pin, and ring
      pin) for treatment of patella fractures by performing a meta-analysis. METHODS:
      PubMed and EMBASE databases were searched for all relevant studies. Standardized
      mean difference (SMD) or relative risk (RR) and their corresponding 95%
      confidence intervals (CIs) were calculated for continuous or dichotomous outcomes
      via either a fixed- or random-effect model using Stata 13.0 software. RESULTS:
      Nine literatures involving 949 patients (581 in the KTB group and 368 in the
      control group) were included. Pooled analysis showed there were no differences in
      the success rate, operative time, healing time, and number of infections between
      patients undergoing KTB and others. However, the incidence of complications (RR =
      8.04, 95% CI = 4.45-14.53; p < 0.001) and VAS (SMD = 0.642, 95% CI = 0.22-1.06; p
      = 0.003) were lower, while flexion degree (SMD = - 0.70 95% CI = - 1.04-- 0.36; p
      < 0.001), Bostman joint function score (SMD = - 0.68, 95% CI = - 1.10-- 0.27; p =
      0.001), Iowa knee score (RR = 0.88, 95% CI = 0.81-0.96; p = 0.004), and Lysholm
      score (SMD = - 0.71, 95% CI = - 1.10-- 0.32; p < 0.001) were significantly higher
      in patients undergoing alternative approaches than the KTB. Subgroup analysis
      also demonstrated the cannulated screw fixation was superior to KTB in reducing
      the incidence of complications. CONCLUSIONS: Alternative treatments may be
      effective for management of patella fractures and should be attempted to be
      popularized in clinic.

PMID- 30185203
TI  - Analysis of the trend of malaria prevalence in Ataye, North Shoa, Ethiopia
      between 2013 and 2017.
AB  - BACKGROUND: Malaria is one of the major public health problems worldwide. In
      Ethiopia, there is a significant decline in disease burden; however, the overall
      trend of malaria prevalence is not studied or well-documented in different
      localities. Hence, the initiation of this study was to analyse the 5-year trends
      of malaria prevalence in Ataye, North Shoa, Ethiopia. METHODS: A retrospective
      laboratory record review was conducted in Ataye Hospital, North-Shoa, Ethiopia.
      Malaria data reported from 2013 to 2017 were carefully reviewed from January to
      March 2018. RESULTS: A total of 31,810 blood films were prepared and examined
      from malaria-suspected patients at Ataye District Hospital from 2013 to 2017. Of
      the examined blood films, 2670 (8.4%) were microscopically confirmed malaria
      cases. The trend of malaria prevalence in the present study seems non-
      fluctuating. Plasmodium falciparum and Plasmodium vivax accounted for 2087
      (78.2%) and 557 (20.9%) cases, respectively. From total positive cases, 1.0% of
      cases were mixed P. falciparum/P. vivax infections, and that no Plasmodium
      malariae and Plasmodium ovale infections were found by malaria microscopists.
      Malaria cases were higher in males 1584 (5.0%) than females 1086 (3.4%). With
      regard to age groups, higher numbers of malaria cases were observed in age group
      15-45 years old. Malaria cases were high in spring (September to December), which
      is a peak malaria transmission period in Ethiopia. CONCLUSION: Malaria is still
      among the major public health problems in the country. P. falciparum is the
      dominant species in the study area followed by P. vivax. Enhancing malaria
      detection and speciation skill of laboratory personnel and scaling up malaria
      control and prevention activities are very crucial to significantly reduce the
      burden of malaria in the study area.

PMID- 30185205
TI  - Prehospital infection control and prevention in Denmark: a cross-sectional study
      on guideline adherence and microbial contamination of surfaces.
AB  - BACKGROUND: Prehospital acute care and treatment have become more complex, and
      while invasive procedures are standard procedures, focus on infection control and
      prevention is scarce. We aimed to evaluate guideline adherence, microbial
      contamination, and associated risk factors. METHODS: In a nationwide cross
      sectional study, we evaluated guideline adherence to thorough cleaning (TC) once
      a day, and moderate cleaning (MC) in-between patient courses. Microbial
      contamination on hand-touch sites (HTS) and provider-related sites (PRS) was
      assessed by total aerobic colony forming units (CFU) and presence of selected
      pathogens, using swab and agar imprints. Also, microbial contamination was
      assessed in relation to potential risk factors. RESULTS: 80 ambulances and
      emergency medical service (EMS) providers were enrolled. Adherence to guidelines
      regarding TC was 35%, but regarding MC it was 100%. In total, 129 (27%) of 480
      HTS presented a total CFU > 2.5/cm2 and/or pathogenic growth, indicating hygiene
      failures. The prevalence of selected pathogens on HTS was: S. aureus 7%;
      Enterococcus 3% and Enterobacteriaceae 1%. Total CFU on the PRS ranged from 0 to
      250/cm2, and the prevalence of pathogens was 18% (S. aureus 15%, Enterococcus 3%
      and Enterobacteriaceae 0.3%). Methicillin-resistant S. aureus was found in one
      sample, and Vancomycin-resistant Enterococcus in two. No Enterobacteriaceae with
      extended-spectrum beta-lactamases were recorded. CONCLUSION: Guideline adherence
      was suboptimal, and many HTS did not comply fully with proposed standards for
      cleanliness. Pathogens were demonstrated on both HTS and PRS, indicating that the
      EMS may be a source of infection in hospitalized patients. Moreover, cleaning
      effort and time appears associated with microbial contamination, but a
      comprehensive investigation of risk factors is needed.

PMID- 30185204
TI  - Progress toward eliminating TB and HIV deaths in Brazil, 2001-2015: a spatial
      assessment.
AB  - BACKGROUND: Brazil has high burdens of tuberculosis (TB) and HIV, as previously
      estimated for the 26 states and the Federal District, as well as high levels of
      inequality in social and health indicators. We improved the geographic detail of
      burden estimation by modelling deaths due to TB and HIV and TB case fatality
      ratios for the more than 5400 municipalities in Brazil. METHODS: This ecological
      study used vital registration data from the national mortality information system
      and TB case notifications from the national communicable disease notification
      system from 2001 to 2015. Mortality due to TB and HIV was modelled separately by
      cause and sex using a Bayesian spatially explicit mixed effects regression model.
      TB incidence was modelled using the same approach. Results were calibrated to the
      Global Burden of Disease Study 2016. Case fatality ratios were calculated for TB.
      RESULTS: There was substantial inequality in TB and HIV mortality rates within
      the nation and within states. National-level TB mortality in people without HIV
      infection declined by nearly 50% during 2001 to 2015, but HIV mortality declined
      by just over 20% for males and 10% for females. TB and HIV mortality rates for
      municipalities in the 90th percentile nationally were more than three times rates
      in the 10th percentile, with nearly 70% of the worst-performing municipalities
      for male TB mortality and more than 75% for female mortality in 2001 also in the
      worst decile in 2015. The same municipality ranking metric for HIV was observed
      to be between 55% and 61%. Within states, the TB mortality rate ratios by sex for
      municipalities in the worst decile versus the best decile varied from 1.4 to 2.9,
      and HIV varied from 1.4 to 4.2. The World Health Organization target case
      fatality rate for TB of less than 10% was achieved in 9.6% of municipalities for
      males versus 38.4% for females in 2001 and improved to 38.4% and 56.6% of
      municipalities for males versus females, respectively, by 2014. CONCLUSIONS:
      Mortality rates in municipalities within the same state exhibited nearly as much
      relative variation as within the nation as a whole. Monitoring the mortality
      burden at this level of geographic detail is critical for guiding precision
      public health responses.

PMID- 30185206
TI  - Imaging dose and secondary cancer risk in image-guided radiotherapy of pediatric
      patients.
AB  - BACKGROUND: Daily image-guided radiotherapy (IGRT) can contribute to cover
      extended body volumes with low radiation dose. The effect of additional imaging
      dose on secondary cancer development is modelled for a collective of children
      with Morbus Hodgkin. METHODS: Eleven radiotherapy treatment plans from pediatric
      patients with Hodgkin's lymphoma were retrospectively analyzed, including imaging
      dose from scenarios using different energies (kV/MV) and planar/cone-beam
      computed tomography (CBCT) techniques. In addition to assessing the effect of
      imaging dose on organs at risk, the excess average risk (EAR) for developing a
      secondary carcinoma of the lung or breast was modelled. RESULTS: Although the
      variability between the patients is relatively large due to the different target
      volumes, the additional EAR due to imaging can be consistently determined. For
      daily 6MV CBCT, the EAR for developing a secondary cancer at age 50 is over 3
      cases per 104 PY (patient-years) for the female breast and 0.7-0.8 per 104 PY for
      the lungs. This can be decreased by using only planar images (< 1 per 104 PY for
      the breast and 0.1 for the lungs). Similar values are achieved by daily 360
      degrees  kV CBCT (0.44-0.57 per 104 PY for the breast and 0.08 per 104 PY for the
      lungs), which is again reduced for daily 200 degrees  kV CBCT (0.02 per 104 PY
      for the lungs and 0.07-0.08 per 104 PY for the breast). These values increase if
      an older attained age is considered (e.g., for 70 years, by a factor of four for
      the lungs). CONCLUSIONS: Daily imaging can be performed with an additional
      secondary cancer risk of less than 1 per 104 PY if kV CBCT is applied. If MV
      modalities must be chosen, a similar EAR can be achieved with planar images. A
      further reduction in risk is possible if the imaging geometry allows for sparing
      of the breast by a partial rotation underneath the patient.

PMID- 30185207
TI  - ERRalpha suppression enhances the cytotoxicity of the MEK inhibitor trametinib
      against colon cancer cells.
AB  - BACKGROUND: ERRalpha, a constitutive transcription factor that regulates energy
      metabolism, plays an important role in the progression of various tumours.
      However, its role in cell survival and proliferation and its implication in
      targeted therapy in colon cancer remains elusive. METHODS: The expression of
      ERRalpha in colon cancer tissues and cell lines was detected by using western
      blotting and immunohistochemistry. A wound healing assay and a transwell assay
      were performed to examine the migration and invasion of the colon cancer cells. A
      cell viability assay, clonogenic assay, western blot assay and the dual
      luciferase reporter assay were employed to study the interaction between
      trametinib (inhibitor of MEK) and EGF treatment. Flow cytometry, western
      blotting, quantitative reverse-transcription polymerase chain reaction and
      xenograft studies were used to identify whether the combination of trametinib and
      simvastatin had a synergistic effect. RESULTS: ERRalpha positively regulated the
      cell proliferation, migration and invasion of colon cancer cells, and the
      suppression of ERRalpha completely reduced the EGF treatment-induced
      proliferation of colon cancer cells. Further investigation showed that trametinib
      partially restrained the up-regulation of ERRalpha induced by the EGF treatment,
      and ERRalpha inhibition increased the sensitivity of colon cancer cells to
      trametinib. At last, we combined trametinib with simvastatin, a common clinically
      used drug with a new reported function of transcriptional activity inhibition of
      ERRalpha, and found that this combination produced a synergistic effect in
      inhibiting the proliferation and survival of colon cancer cells in vitro as well
      as in vivo. CONCLUSIONS: The present data indicated that ERRalpha acted as an
      oncogene in colon cancer cells, and the combined targeting of ERRalpha and MEK
      might be a promising therapeutic strategy for colon cancer treatment.

PMID- 30185208
TI  - Rare disease registries: potential applications towards impact on development of
      new drug treatments.
AB  - BACKGROUND: Low prevalence, lack of knowledge about the disease course, and
      phenotype heterogeneity hamper the development of drugs for rare diseases. Rare
      disease registries (RDRs) can be helpful by playing a role in understanding the
      course of the disease, and providing information necessary for clinical trial
      design, if designed and maintained properly. We describe the potential
      applications of a RDR and what type of information should be incorporated to
      support the design of clinical trials in the process of drug development, based
      on a broad inventory of registry experience. We evaluated two existing RDRs in
      more detail to check the completeness of these RDRs for trial design. RESULTS:
      Before and during the application for regulatory approval a RDR can improve the
      efficiency and quality in clinical trial design by informing the sample size
      calculation and expected disease course. In exceptional circumstances information
      from RDRs has been used as historical controls for a one-armed clinical trial,
      and high quality RDRs may be used for registry-based randomized controlled
      trials. In the post marketing phase of (conditional) drug approval a disease
      specific RDR is likely to provide more relevant information than a product
      specific registry. CONCLUSIONS: A RDR can be very helpful to improve the
      efficiency and quality of clinical trial design in several ways. To enable the
      applicability and optimal use of a RDR longitudinal data collection is
      indispensable, and specific data collection, prepared for repeated measurement,
      is needed. The developed checklist can help to define the appropriate variables
      to include. Attention should be paid to the inclusion of patient-relevant outcome
      measures in the RDR from the start. More research and experience is needed on the
      possibilities and limitations of combining RDR information with clinical trial
      data to maximize the availability of relevant evidence for regulatory decisions
      in rare diseases.

PMID- 30185209
TI  - A novel experimental setup for evaluating the stiffness of ankle foot orthoses.
AB  - OBJECTIVE: The purpose of this study was the construction of a new semi-automated
      experimental setup for the evaluation of the stiffness of ankle foot orthoses
      (AFOs) around an axis aligned to the anatomical ankle joint during the second
      rocker of the gait. The setup, developed in close collaboration with the
      orthopedic device company V!GO NV (Wetteren, Belgium), allows measurement of
      plantarflexion and dorsiflexion in the sagittal plane for a maximal range of
      motion of 50 degrees  (- 25 degrees  plantarflexion up to 25 degrees 
      dorsiflexion) in a non-destructive way. RESULTS: The mechanical properties of
      four 3D printed AFOs are investigated, based on the ranges of motion derived from
      the gait assessment of the patients when they walked with their AFO. The
      reliability of the stiffness measures was studied by the evaluation of the test
      retest repeatability and the intra-tester and inter-tester variability. These
      studies revealed that the ankle stiffness can be measured with high reliability
      (ICC = 0.94-1.00). The obtained outcomes indicate that the experimental setup
      could be applied to measure the ankle stiffness of any topology of AFOs and, in
      the future, help finding the correlation with the information coming from the
      gait assessment of the patients.

PMID- 30185210
TI  - Transcranial magnetic stimulation intervention in Alzheimer's disease: a research
      proposal for a randomized controlled trial.
AB  - OBJECTIVE: Alzheimer's disease is a major health problem in our society. To date,
      pharmacological treatments have obtained poor results and there is a growing
      interest in finding non-pharmacological interventions for this disease.
      Transcranial magnetic stimulation (TMS) is a non-invasive technique that is able
      to induce changes in brain activity and long-term modifications in impaired
      neural networks, becoming a promising clinical intervention. Our goal is to study
      the benefit of individualized TMS targeting based on the patient's functional
      connectivity (personalized targeting), and short duration TMS protocol, instead
      of current non-individualized and longer session approaches. A double blind
      randomized controlled trial will be conducted to assess the effects of TMS
      treatment immediately, 1 month, 3 months and 6 months after the end of the
      intervention. Fifty-four patients with a diagnosis of Alzheimer's disease will be
      randomly allocated into experimental (active TMS), sham control, or conventional
      intervention control group. We will quantify changes in cognitive, functional,
      and emotional deficits in Alzheimer patients, as well as the functional
      connectivity changes induced by the TMS treatment. RESULTS: We expect to
      demonstrate that personalized TMS intervention has a measurable positive impact
      in cognition, emotion, daily living activities and brain connectivity, thus
      representing a potential treatment for Alzheimer's disease. Trial registration
      The trial has been prospectively registered at ClinicalTrials.gov, identifier
      NCT03121066. Date of registration: 04/19/2017.

PMID- 30185211
TI  - Effect of intravitreal dexamethasone on macular edema in von Hippel-Lindau
      disease assessed using swept-source optical coherence tomography: a case report.
AB  - BACKGROUND: Von Hippel-Lindau disease is a rare hereditary syndrome caused by
      germinal mutations in a von Hippel-Lindau tumor-suppressing gene. Retinal
      hemangioblastoma is the ocular hallmark lesion of von Hippel-Lindau disease. CASE
      PRESENTATION: A 20-year-old Caucasian woman presented to our institution with
      painless visual impairment in the right eye. A fundus ophthalmoscopic evaluation
      and swept-source optical coherence tomographic examination revealed a retinal
      hemangioblastoma associated with cystoid macular edema. On the basis of the
      clinical ocular findings and genetic analysis, von Hippel-Lindau disease was
      diagnosed. Following an intravitreal injection of ranibizumab, off-label
      administration of intravitreal dexamethasone was considered to reduce the edema.
      An almost complete resolution of the edema in the macular area was observed 1
      week after the injection. Finally, laser photocoagulation and transconjunctival
      cryotherapy were performed; the patient developed "ablatio fugax" after
      cryotherapy. CONCLUSIONS: In our experience, intravitreal dexamethasone
      administration has proven to be a useful tool for reducing retinal
      hemangioblastoma-related macular edema in von Hippel-Lindau disease and may be
      considered a potentially valuable treatment that can be used in combination with
      other therapies.

PMID- 30185214
TI  - Arsenic trioxide and all-trans retinoic acid (ATRA) treatment for acute
      promyelocytic leukemia in all risk groups: study protocol for a randomized
      controlled trial.
AB  - BACKGROUND: The treatment of acute promyelocytic leukemia (APL) has been
      revolutionized in the past two decades by the advent of all-trans retinoic acid
      (ATRA) and arsenic trioxide (ATO). It suggests that non-high-risk APL patients
      can be cured without chemotherapy. However, ATRA plus chemotherapy is still the
      standard therapy for the high-risk patients. Central nervous system (CNS) relapse
      remains a significant cause of treatment failure in high-risk patients. However,
      increasing the ATO concentration in cerebrospinal fluid (CSF) may reduce CNS
      relapse in high-risk patients. Mannitol can allow ATO to penetrate the blood
      brain barrier (BBB) and reach therapeutically effective levels in the CSF. It is
      used for the treatment of CNS relapse in patients APL. We compare ATRA-ATO with
      ATRA-ATO plus chemotherapy in both high-risk and non-high-risk patients with APL.
      METHODS: This study was designed as a multicenter randomized controlled trial.
      Patients with APL were randomly assigned into two groups: the ATRA-ATO group
      (experimental group) and the ATRA-ATO plus chemotherapy group (control group).
      The experimental group receives therapy with ATRA-ATO for induction,
      consolidation and maintenance therapy. In the high-risk patients, mannitol will
      be used with ATO in the consolidation and maintenance therapy. Hydroxyurea will
      be used in patients who developed leukocytosis in the induction therapy. The
      control group receives therapy with ATRA-ATO plus chemotherapy for induction and
      consolidation therapy. DISCUSSION: In this study, a randomized clinical trial
      design is described. It aims to compare the efficacy of ATRA-ATO versus ATRA-ATO
      plus chemotherapy in all-risk patients with APL. TRIAL REGISTRATION: Chinese
      Clinical Trials Registry, ID: ChiCTR-IPR- 15006821 . Registered on 27 July 2015.

PMID- 30185213
TI  - Clinical dementia severity associated with ventricular size is differentially
      moderated by cognitive reserve in men and women.
AB  - BACKGROUND: Interindividual differences in cognitive reserve (CR) are associated
      with complex and dynamic clinical phenotypes observed in cognitive impairment and
      dementia. We tested whether (1) CR early in life (E-CR; measured by education and
      IQ), (2) CR later in life (L-CR; measured by occupation), and (3) CR panel (CR-P)
      with the additive effects of E-CR and L-CR, act as moderating factors between
      baseline ventricular size and clinical dementia severity at baseline and across 2
      years. We further examined whether this moderation is differentially represented
      by sex. METHODS: We examined a longitudinal model using patients (N = 723; mean
      age = 70.8 +/- 9.4 years; age range = 38-90 years; females = 374) from the
      Sunnybrook Dementia Study. The patients represented Alzheimer's disease (n =
      439), mild cognitive impairment (n = 77), vascular cognitive impairment (n = 52),
      Lewy body disease (n = 30), and frontotemporal dementia (n = 125). Statistical
      analyses included (1) latent growth modeling to determine how clinical dementia
      severity changes over 2 years (measured by performance on the Dementia Rating
      Scale), (2) confirmatory factor analysis to establish a baseline E-CR factor, and
      (3) path analysis to predict dementia severity. Baseline age (continuous) and
      Apolipoprotein E status (E4-/E4+) were included as covariates. RESULTS: The
      association between higher baseline ventricular size and dementia severity was
      moderated by (1) E-CR and L-CR and (2) CR-P. This association was differentially
      represented in men and women. Specifically, men in only the low CR-P had higher
      baseline clinical dementia severity with larger baseline ventricular size.
      However, women in the low CR-P showed the (1) highest baseline dementia severity
      and (2) fastest 2-year decline with larger baseline ventricular size.
      CONCLUSIONS: Clinical dementia severity associated with ventricular size may be
      (1) selectively moderated by complex and additive CR networks and (2)
      differentially represented by sex. TRIALS REGISTRATION: ClinicalTrials.gov,
      NCT01800214 . Registered on 27 February 2013.

PMID- 30185212
TI  - The putative tumour suppressor miR-1-3p modulates prostate cancer cell
      aggressiveness by repressing E2F5 and PFTK1.
AB  - BACKGROUND: Previous studies report that miR-1-3p, a member of the microRNA-1
      family (miR-1), and functions as a tumor suppressor in several different cancers.
      However, little is known regarding the biological role and intrinsic regulatory
      mechanisms of miR-1-3p in prostate cancer (PCa). METHODS: In this study, the
      expression levels of miR-1-3p were first examined in PCa cell lines and tumor
      tissues by RT-qPCR and bioinformatics. The in vitro and in vivo functional effect
      of miR-1-3p was examined further. A luciferase reporter assay was conducted to
      confirm target associations. RESULTS: We found that miR-1-3p was significantly
      downregulated in advanced PCa tissues and cell lines. Low miR-1-3p levels were
      strongly associated with aggressive clinicopathological features and poor
      prognosis in PCa patients. Ectopic expression of miR-1-3p in 22RV1 and LncaP
      cells was sufficient to prevent tumor cell growth and cell cycle progression in
      vitro and in vivo. Further mechanistic studies revealed that miR-1-3p could
      directly target the mRNA 3'- untranslated region (3'- UTR) of two central cell
      cycle genes, E2F5 and PFTK1, and could suppress their mRNA and protein
      expression. In addition, knockdown of E2F5 and PFTK1 mimicked the tumor
      suppressive effects of miR-1-3p overexpression on PCa progression. Conversely,
      concomitant knockdown of miR-1-3p and E2F5 and PFTK1 substantially reversed the
      inhibitory effects of either E2F5 or PFTK1 silencing alone. CONCLUSION: These
      data highlight an important role for miR-1-3p in the regulation of proliferation
      and cell cycle in the molecular etiology of PCa and indicate the potential for
      miR-1-3p in applications furthering PCa prognostics and therapeutics.

PMID- 30185215
TI  - ADHD prevalence estimates in Italian children and adolescents: a methodological
      issue.
AB  - BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is recognized as the
      most common, and most studied, developmental age disorder. Basic information,
      such as the most appropriate case definition and the best way to evaluate the
      disorder's prevalence rate, however, remains an open issue. METHODS: A
      comprehensive meta-analysis on the epidemiology of ADHD in Italy, which was
      lacking from the literature, was therefore performed to attempt to estimate the
      actual prevalence rate of ADHD, highlighting conceptual and quantitative
      differences between clinical-diagnosis and survey-based symptoms studies. The
      Medline, Embase, and PsycINFO databases, and the grey literature, were searched
      up to January 2018. The review was laid out in three main sections: an overall
      prevalence estimate, an epidemiological profile of ADHD symptoms, and an attempt
      to define the actual rate of ADHD diagnosis, as emerged from Italian studies.
      RESULTS: A total of 15 unique studies were included. These contributed to
      estimating the prevalence of ADHD in 67,838 subjects aged 5-17, representing 9 of
      the 20 regions (45%) of Italy. Overall, the pooled prevalence of ADHD was 2.9%
      (range: 1.1-16.7%). When distinguishing studies based on case definition,
      however, we found an average prevalence estimate, based on symptoms criteria, of
      5.9% (range: 1.4 to 16.7%) and a best-estimate prevalence rate of 1.4% (range:
      1.1 to 3.1%). CONCLUSIONS: Following the case definition for epidemiological
      studies of ADHD, counting only subjects with an ADHD diagnosis performed and
      confirmed by clinical assessment would reduce the wide variability in prevalence
      estimates, and, above all, would both describe the real rate of subjects
      suffering from ADHD disorder and avoid misdiagnosis.

PMID- 30185217
TI  - From population to individuals: a new indicator for evaluating the
      appropriateness of clinical application of antibiotics.
AB  - BACKGROUND: This study aims to establish a new indicator based on the anatomical
      therapeutic chemical/defined daily dose (ATC/DDD) system. METHODS: Utilization
      data of antibiotics of inpatients in a university hospital were used to calculate
      the indicators of use rate (UR), use density (UD), and ratio of use density to
      use rate (UD/UR). According to the professional characteristics, the recommended
      values of UD/UR in different departments were established respectively. Crosswise
      comparison and appropriateness evaluation between different treatment groups with
      the same profession were performed. For individual inpatients with abnormally
      increased drug utilization index (DUI) and ratios of antimicrobial course to
      length of stay (C/S), detailed analysis was performed to examine whether any
      irrational drug utilization occurred. RESULTS: The indicator UD/UR combines both
      dose and duration of treatment, which were the two main factors affecting the
      appropriateness of clinical application of antibiotics. Thus, it can more
      sensitively reveal the drug utilization of inpatients receiving antibiotics.
      UD/UR is also more suitable for evaluating the clinical appropriateness of
      antibiotic application than the macroscopic indicator, total UD, and could be
      applied at the macroscopic and microscopic levels. CONCLUSIONS: The ratio UD/UR
      has great practical value and can serve as a reference for evaluating the
      appropriateness of clinical application of antibiotics.

PMID- 30185216
TI  - Evaluation of anti-PD-1-based therapy against triple-negative breast cancer
      patient-derived xenograft tumors engrafted in humanized mouse models.
AB  - BACKGROUND: Breast cancer has been considered not highly immunogenic, and few
      patients benefit from current immunotherapies. However, new strategies are aimed
      at changing this paradigm. In the present study, we examined the in vivo activity
      of a humanized anti-programmed cell death protein 1 (anti-PD-1) antibody against
      triple-negative breast cancer (TNBC) patient-derived xenograft (PDX) tumor
      models. METHODS: To circumvent some of the limitations posed by the lack of
      appropriate animal models in preclinical studies of immunotherapies, partially
      human leukocyte antigen-matched TNBC PDX tumor lines from our collection, as well
      as human melanoma cell lines, were engrafted in humanized nonobese
      diabetic/severe combined immunodeficiency IL2Rgammanull (hNSG) mice obtained by
      intravenous injection of CD34+ hematopoietic stem cells into nonlethally
      irradiated 3-4-week-old mice. After both PDXs and melanoma cell xenografts
      reached ~ 150-200 mm3, animals were treated with humanized anti-PD-1 antibody or
      anti-CTLA-4 and evaluated for tumor growth, survival, and potential mechanism of
      action. RESULTS: Human CD45+, CD20+, CD3+, CD8+, CD56+, CD68+, and CD33+ cells
      were readily identified in blood, spleen, and bone marrow collected from hNSG, as
      well as human cytokines in blood and engrafted tumors. Engraftment of TNBC PDXs
      in hNSG was high (~ 85%), although they grew at a slightly slower pace and
      conserved their ability to generate lung metastasis. Human CD45+ cells were
      detectable in hNSG-harbored PDXs, and consistent with clinical observations, anti
      PD-1 antibody therapy resulted in both a significant reduction in tumor growth
      and increased survival in some of the hNSG PDX tumor lines, whereas no such
      effects were observed in the corresponding non-hNSG models. CONCLUSIONS: This
      study provides evidence associated with anti-PD-1 immunotherapy against TNBC
      tumors supporting the use of TNBC PDXs in humanized mice as a model to overcome
      some of the technical difficulties associated with the preclinical investigation
      of immune-based therapies.

PMID- 30185219
TI  - Unique microglia recovery population revealed by single-cell RNAseq following
      neurodegeneration.
AB  - Microglia are brain immune cells that constantly survey their environment to
      maintain homeostasis. Enhanced microglial reactivity and proliferation are
      typical hallmarks of neurodegenerative diseases. Whether specific disease-linked
      microglial subsets exist during the entire course of neurodegeneration, including
      the recovery phase, is currently unclear. Taking a single-cell RNA-sequencing
      approach in a susceptibility gene-free model of nerve injury, we identified a
      microglial subpopulation that upon acute neurodegeneration shares a conserved
      gene regulatory profile compared to previously reported chronic and destructive
      neurodegeneration transgenic mouse models. Our data also revealed rapid shifts in
      gene regulation that defined microglial subsets at peak and resolution of
      neurodegeneration. Finally, our discovery of a unique transient microglial
      subpopulation at the onset of recovery may provide novel targets for modulating
      microglia-mediated restoration of brain health.

PMID- 30185218
TI  - Epigenetic regulation of MAGE family in human cancer progression-DNA methylation,
      histone modification, and non-coding RNAs.
AB  - The melanoma antigen gene (MAGE) proteins are a group of highly conserved family
      members that contain a common MAGE homology domain. Type I MAGEs are relevant
      cancer-testis antigens (CTAs), and originally considered as attractive targets
      for cancer immunotherapy due to their typically high expression in tumor tissues
      but restricted expression in normal adult tissues. Here, we reviewed the recent
      discoveries and ideas that illustrate the biological functions of MAGE family in
      cancer progression. Furthermore, we also highlighted the current understanding of
      the epigenetic mechanism of MAGE family expression in human cancers.

PMID- 30185221
TI  - Nerve root block versus surgery (NERVES) for the treatment of radicular pain
      secondary to a prolapsed intervertebral disc herniation: study protocol for a
      multi-centre randomised controlled trial.
AB  - BACKGROUND: Sciatica is a common condition reported to affect over 3% of the UK
      population at any time and is often caused by a prolapsed intervertebral disc
      (PID). Although the duration and severity of symptoms can vary, pain persisting
      beyond 6 weeks is unlikely to recover spontaneously and may require investigation
      and treatment. Currently, there is no specific care pathway for sciatica in the
      National Health Service (NHS), and no direct comparison exists between surgical
      microdiscectomy and transforaminal epidural steroid injection (TFESI). The NERVES
      (NErve Root block VErsus Surgery) trial aims to address this by comparing
      clinical and cost-effectiveness of surgical microdiscectomy and TFESI to treat
      sciatica secondary to a PID. METHODS/DESIGN: A total of 163 patients were
      recruited from NHS out-patient clinics across the UK and randomised to either
      microdiscectomy or TFESI. Adult patients (aged 16-65 years) with sciatic pain
      endured for between 6 weeks and 12 months are eligible if their symptoms have not
      been improved by at least one form of conservative (non-operative) treatment and
      they are willing to provide consent. Patients will be excluded if they present
      with neurological deficit or have had previous surgery at the same level. The
      primary outcome is patient-reported disability measured using the Oswestry
      Disability Questionnaire (ODQ) score at 18 weeks post randomisation and secondary
      outcomes include disability and pain scales using numerical pain ratings,
      modified Roland-Morris and Core Outcome Measures Index at 12-weekly intervals,
      and patient satisfaction at 54 weeks. Cost-effectiveness and quality of life
      (QOL) will be assessed using the EQ-5D-5 L and self-report cost data at 12-weekly
      intervals and Hospital Episode Statistics (HES) data. Adverse event data will be
      collected. Analysis will follow the principle of intention-to-treat. DISCUSSION:
      NERVES is the first trial to evaluate the comparative clinical and cost
      effectiveness of microdiscectomy to local anaesthetic and steroid administered
      via TFESI. The results of this research may facilitate the development of an
      evidence-based treatment strategy for patients with sciatica. TRIAL REGISTRATION:
      ISRCTN, ID: ISRCTN04820368 . Registered on 5 June 2014. EudraCT EudraCT2014
      002751-25. Registered on 8 October 2014.

PMID- 30185222
TI  - Betanodavirus infection in primary neuron cultures from sole.
AB  - Nervous necrosis virus (NNV), G. Betanodavirus, is the causative agent of viral
      encephalopathy and retinopathy, a disease that causes mass mortalities in a wide
      range of fish species. Betanodaviruses are neurotropic viruses and their
      replication in the susceptible fish species seems to be almost entirely
      restricted to nerve tissue. However, none of the cell lines used for NNV
      propagation has a nervous origin. In this study, first we established a protocol
      for the primary culture of neurons from Senegalese sole, which made it possible
      to further study virus-host cell interactions. Then, we compared the replication
      of three NNV strains with different genotypes (SJNNV, RGNNV and a RGNNV/SJNNV
      reassortant strain) in sole neuron primary cultures and E-11 cells. In addition,
      to study how two amino acid substitutions at the c-terminal of the capsid protein
      (positions 247 and 270) affect the binding to cell receptors, a recombinant
      strain was also tested. The results show that sole neural cells enabled
      replication of all the tested NNV strains. However, the recombinant strain shows
      a clearly delayed replication when compared with the wt strain. This delay was
      not observed in virus replicating in E-11 cells, suggesting a viral interaction
      with different cell receptors. The establishment of a sole primary neuronal
      culture protocol provides an important tool for research into betanodavirus
      infection in sole.

PMID- 30185220
TI  - The CO2-dependence of Brucella ovis and Brucella abortus biovars is caused by
      defective carbonic anhydrases.
AB  - Brucella bacteria cause brucellosis, a major zoonosis whose control requires
      efficient diagnosis and vaccines. Identification of classical Brucella spp. has
      traditionally relied on phenotypic characterization, including surface antigens
      and 5-10% CO2 necessity for growth (CO2-dependence), a trait of Brucella ovis and
      most Brucella abortus biovars 1-4 strains. Although molecular tests are replacing
      phenotypic methods, CO2-dependence remains of interest as it conditions isolation
      and propagation and reflects Brucella metabolism, an area of active research.
      Here, we investigated the connection of CO2-dependence and carbonic anhydrases
      (CA), the enzymes catalyzing the hydration of CO2 to the bicarbonate used by
      anaplerotic and biosynthetic carboxylases. Based on the previous demonstration
      that B. suis carries two functional CAs (CAI and CAII), we analyzed the CA
      sequences of CO2-dependent and -independent brucellae and spontaneous mutants.
      The comparisons strongly suggested that CAII is not functional in CO2-dependent
      B. abortus and B. ovis, and that a modified CAII sequence explains the CO2
      independent phenotype of spontaneous mutants. Then, by mutagenesis and
      heterologous plasmid complementation and chromosomal insertion we proved that CAI
      alone is enough to support CO2-independent growth of B. suis in rich media but
      not of B. abortus in rich media or B. suis in minimal media. Finally, we also
      found that insertion of a heterologous active CAII into B. ovis reverted the CO2
      dependence but did not alter its virulence in the mouse model. These results
      allow a better understanding of central aspects of Brucella metabolism and, in
      the case of B. ovis, provide tools for large-scale production of diagnostic
      antigens and vaccines.

PMID- 30185224
TI  - Correction to: Intracellular hypoxia measured by F-18 fluoromisonidazole positron
      emission tomography has prognostic impact in patients with estrogen-receptor
      positive breast (BRCR-D17-00693).
AB  - After the publication of this article [1], we noticed that in Fig. 2, the
      survival curve images (C and D, lower panel) were incorrect. The corrected Fig. 2
      is presented below. The correction does not affect in any our results and
      conclusions.

PMID- 30185223
TI  - Linking the severity of illness and the weekend effect: a cohort study examining
      emergency department visits.
AB  - BACKGROUND: Despite extensive research on the "weekend effect" i.e., the
      increased mortality associated with hospital admission during weekend, knowledge
      about disease severity in previous studies is limited. The aim of this study is
      to examine patient characteristics, including disease severity, 30-day mortality,
      and length of stay (LOS), according to time of admission to an emergency
      department. METHODS: Our study encompassed all patients admitted to a Danish
      emergency department in 2014-2015. Using data from electronic patient records,
      this study examines patient characteristics including age, gender, Charlson
      Comorbidity Index score, triage score, and primary diagnosis. Triage score and
      transfer to intensive care unit (ICU) were used as indicators of disease
      severity. LOS within the department and within the hospital was examined. Age-
      and sex-standardized 30-day mortality rates comparing patients with the same
      triage score admitted at daytime, evening, and nighttime on weekdays and on
      weekends were computed. To test differences, a Cox regression analysis was added.
      RESULTS: We included 35,459 patient visits, of which 10,435 (32%) started on a
      weekend. There were no large differences in baseline characteristics between
      patients admitted on weekdays and those admitted on weekends. The relative risk
      (RR) for being triaged orange or red was 1.16 (95% confidence interval (CI) 1.06
      1.28, P = 0.0017) for weekend admissions as compared with weekday admissions.
      Weekend admissions were twice as likely as weekday admissions to be transferred
      to the ICU (RR, 1.96; 95% CI 1.53-2.52, P = 0.0000). No significant changes were
      found in LOS. The 30-day mortality rate increased with disease severity
      regardless of time of admission. When comparing the 30-day mortality rate for
      patients with the same triage score, the trend was toward a higher mortality when
      admission occurred during the weekend. Increasing mortality rate was significant
      for patients admitted at evening on weekends with a hazard ratio of 1.32 (95% CI
      1.03-1.70, P = 0.027) when compared with patients admitted on daytime on
      weekdays. CONCLUSIONS: When comparing weekday and weekend admissions, the 30-day
      mortality rate increased for patients admitted at evening on weekends after
      adjusting for comorbidity and triage score, indicating that the weekend effect
      was independent of changes in illness severity.

PMID- 30185225
TI  - Renal cancer: new models and approach for personalizing therapy.
AB  - BACKGROUND: Clear cell RCC (ccRCC) accounts for approximately 75% of the renal
      cancer cases. Surgery treatment seems to be the best efficacious approach for the
      majority of patients. However, a consistent fraction (30%) of cases progress
      after surgery with curative intent. It is currently largely debated the use of
      adjuvant therapy for high-risk patients and the clinical and molecular parameters
      for stratifying beneficiary categories. In addition, the treatment of advanced
      forms lacks reliable driver biomarkers for the appropriated therapeutic choice.
      Thus, renal cancer patient management urges predictive molecular indicators and
      models for therapy-decision making. METHODS: Here, we developed and optimized new
      models and tools for ameliorating renal cancer patient management. We isolated
      from fresh tumor specimens heterogeneous multi-clonal populations showing
      epithelial and mesenchymal characteristics coupled to stem cell phenotype. These
      cells retained long lasting-tumor-propagating capacity provided a therapy
      monitoring approach in vitro and in vivo while being able to form parental tumors
      when orthotopically injected and serially transplanted in immunocompromised
      murine hosts. RESULTS: In line with recent evidence of multiclonal cancer
      composition, we optimized in vitro cultures enriched of multiple tumor
      propagating populations. Orthotopic xenograft masses recapitulated morphology,
      grading and malignancy of parental cancers. High-grade but not the low-grade
      neoplasias, resulted in efficient serial transplantation in mice. Engraftment
      capacity paralleled grading and recurrence frequency advocating for a prognostic
      value of our developed model system. Therefore, in search of novel molecular
      indicators for therapy decision-making, we used Reverse-Phase Protein Arrays
      (RPPA) to analyze a panel of total and phosphorylated proteins in the isolated
      populations. Tumor-propagating cells showed several deregulated kinase cascades
      associated with grading, including angiogenesis and m-TOR pathways. CONCLUSIONS:
      In the era of personalized therapy, the analysis of tumor propagating cells may
      help improve prediction of disease progression and therapy assignment. The
      possibility to test pharmacological response of ccRCC stem-like cells in vitro
      and in orthotopic models may help define a pharmacological profiling for future
      development of more effective therapies. Likewise, RPPA screening on patient
      derived populations offers innovative approach for possible prediction of therapy
      response.

PMID- 30185227
TI  - First cross-sectional, molecular epidemiological survey of Cryptosporidium,
      Giardia and Enterocytozoon in alpaca (Vicugna pacos) in Australia.
AB  - BACKGROUND: Eukaryotic pathogens, including Cryptosporidium, Giardia and
      Enterocytozoon, have been implicated in neonatal diarrhoea, leading to marked
      morbidity and mortality in the alpaca (Vicugna pacos) and llama (Lama glama)
      around the world. Australia has the largest population of alpacas outside of
      South America, but very little is known about these pathogens in alpaca
      populations in this country. Here, we undertook the first molecular
      epidemiological survey of Cryptosporidium, Giardia and Enterocytozoon in V. pacos
      in Australia. METHODS: A cross-sectional survey of 81 herds, comprising alpacas
      of 6 weeks to 26 years of age, were sampled from the six Australian states
      (Queensland, New South Wales, Victoria, South Australia, Tasmania and Western
      Australia) across the four seasons. PCR-based sequencing was employed, utilising
      genetic markers in the small subunit of the nuclear ribosomal RNA (SSU) and 60
      kilodalton glycoprotein (gp60) genes for Cryptosporidium, triose-phosphate
      isomerase (tpi) gene for Giardia duodenalis and the internal transcribed spacer
      region (ITS) for Enterocytozoon bieneusi. RESULTS: PCR-based analyses of 81
      faecal DNA samples representing 1421 alpaca individuals detected Cryptosporidium,
      Giardia and/or Enterocytozoon on 15 farms in New South Wales, Victoria and South
      Australia, equating to 18.5% of all samples/herds tested. Cryptosporidium was
      detected on three (3.7%) farms, G. duodenalis on six (7.4%) and E. bieneusi on
      eight (9.9%) in two or all of these three states, but not in Queensland, Tasmania
      or Western Australia. Molecular analyses of selected faecal DNA samples from
      individual alpacas for Cryptosporidium, Giardia and/or Enterocytozoon
      consistently showed that alpacas of <= 6 months of age harboured these pathogens.
      CONCLUSIONS: This first molecular investigation of Cryptosporidium, Giardia and
      Enterocytozoon in alpaca subpopulations in Australia has identified species and
      genotypes that are of likely importance as primary pathogens of alpacas,
      particularly young crias, and some genotypes with zoonotic potential. Although
      the prevalence established here in the alpaca subpopulations studied is low, the
      present findings suggest that crias are likely reservoirs of infections to
      susceptible alpacas and/or humans. Future studies should focus on investigating
      pre-weaned and post-weaned crias, and on exploring transmission patterns to
      establish what role particular genotypes play in neonatal or perinatal diarrhoea
      in alpacas and in zoonotic diseases in different states of Australia.

PMID- 30185228
TI  - A phase Ib study of pictilisib (GDC-0941) in combination with paclitaxel, with
      and without bevacizumab or trastuzumab, and with letrozole in advanced breast
      cancer.
AB  - BACKGROUND: This phase Ib study (NCT00960960) evaluated pictilisib (GDC-0941; pan
      phosphatidylinositol 3-kinase inhibitor) plus paclitaxel, with and without
      bevacizumab or trastuzumab, or in combination with letrozole, in patients with
      locally recurrent or metastatic breast cancer. METHODS: This was a three-part
      multischedule study. Patients in parts 1 and 2, which comprised 3 + 3 dose
      escalation and cohort expansion stages, received pictilisib (60-330 mg) plus
      paclitaxel (90 mg/m2) with and without bevacizumab (10 mg/kg) or trastuzumab (2-4
      mg/kg). In part 3, patients received pictilisib (260 mg) plus letrozole (2.5 mg).
      Primary objectives were evaluation of safety and tolerability, identification of
      dose-limiting toxicities (DLTs) and the maximum tolerated dose (MTD) of
      pictilisib, and recommendation of a phase II dosing regimen. Secondary endpoints
      included pharmacokinetics and preliminary antitumor activity. RESULTS: Sixty-nine
      patients were enrolled; all experienced at least one adverse event (AE). Grade >=
      3 AEs, serious AEs, and AEs leading to death were reported in 50 (72.5%), 21
      (30.4%), and 2 (2.9%) patients, respectively. Six (8.7%) patients reported a DLT,
      and the MTD and recommended phase II pictilisib doses were established where
      possible. There was no pictilisib-paclitaxel drug-drug interaction. Two (3.4%)
      patients experienced complete responses, and 17 (29.3%) patients had partial
      responses. CONCLUSIONS: Combining pictilisib with paclitaxel, with and without
      bevacizumab or trastuzumab, or letrozole, had a manageable safety profile in
      patients with locally recurrent or metastatic breast cancer. The combination had
      antitumor activity, and the additive effect of pictilisib supported further
      investigation in a randomized study. TRIAL REGISTRATION: ClinicalTrials.gov,
      NCT00960960 . Registered on August 13, 2009.

PMID- 30185229
TI  - A correction to the age-adjustment of the GH-2000 score used in the detection of
      growth hormone misuse.
AB  - OBJECTIVE: The GH-2000 biomarker test has been introduced by the World Anti
      Doping Agency as a method of detecting growth hormone misuse in professional
      sport. The test involves the measurement insulin-like growth factor-I and the
      amino-terminal pro-peptide of type III collagen (P-III-NP) which increase in a
      dose-dependent manner in response to GH. These measurements are combined in sex
      specific formulae that include an age adjustment. The original age adjustment
      overcorrects the effect of age in male athletes and could potentially place older
      men at a disadvantage. The purpose of this note is to investigate the performance
      of a previously suggested correction term in two new and larger data sets.
      RESULTS: The GH-2000 score was calculated for 7307 samples obtained from 15
      accredited WADA laboratories in 2017 and 3916 samples measured at Drug Control
      Centre, King's College London, UK between 2013 and 2017. The GH-2000 scores were
      investigated for positive age effects using standard regression modelling. As
      previously, all analyses confirmed a positive age effect. Applying the earlier
      suggested correction term of 0.032 * age showed a significant over-correction
      leading to a negative association of the GH-2000 score with age. We now suggest a
      smaller age correction of 0.020 * age, which corresponds to the smallest effect
      found in the earlier studies.

PMID- 30185226
TI  - Alteration of the cutaneous microbiome in psoriasis and potential role in Th17
      polarization.
AB  - BACKGROUND: Psoriasis impacts 1-3% of the world's population and is characterized
      by hyper-proliferation of keratinocytes and increased inflammation. At the
      molecular level, psoriasis is commonly driven by a Th17 response, which serves as
      a major therapeutic target. Microbiome perturbations have been associated with
      several immune-mediated diseases such as atopic dermatitis, asthma, and multiple
      sclerosis. Although a few studies have investigated the association between the
      skin microbiome and psoriasis, conflicting results have been reported plausibly
      due to the lack of standardized sampling and profiling protocols, or to inherent
      microbial variability across human subjects and underpowered studies. To better
      understand the link between the cutaneous microbiota and psoriasis, we conducted
      an analysis of skin bacterial communities of 28 psoriasis patients and 26 healthy
      subjects, sampled at six body sites using a standardized protocol and higher
      sequencing depth compared to previous studies. Mouse studies were employed to
      examine dermal microbial-immune interactions of bacterial species identified from
      our study. RESULTS: Skin microbiome profiling based on sequencing the 16S rRNA V1
      V3 variable region revealed significant differences between the psoriasis
      associated and healthy skin microbiota. Comparing the overall community
      structures, psoriasis-associated microbiota displayed higher diversity and more
      heterogeneity compared to healthy skin bacterial communities. Specific microbial
      signatures were associated with psoriatic lesional, psoriatic non-lesional, and
      healthy skin. Specifically, relative enrichment of Staphylococcus aureus was
      strongly associated with both lesional and non-lesional psoriatic skin. In
      contrast, Staphylococcus epidermidis and Propionibacterium acnes were
      underrepresented in psoriatic lesions compared to healthy skin, especially on the
      arm, gluteal fold, and trunk. Employing a mouse model to further study the impact
      of cutaneous Staphylcoccus species on the skin T cell differentiation, we found
      that newborn mice colonized with Staphylococcus aureus demonstrated strong Th17
      polarization, whereas mice colonized with Staphylococcus epidermidis or un
      colonized controls showed no such response. CONCLUSION: Our results suggest that
      microbial communities on psoriatic skin is substantially different from those on
      healthy skin. The psoriatic skin microbiome has increased diversity and reduced
      stability compared to the healthy skin microbiome. The loss of community
      stability and decrease in immunoregulatory bacteria such as Staphylococcus
      epidermidis and Propionibacterium acnes may lead to higher colonization with
      pathogens such as Staphylococcus aureus, which could exacerbate cutaneous
      inflammation along the Th17 axis.

PMID- 30185230
TI  - The Trem2 R47H Alzheimer's risk variant impairs splicing and reduces Trem2 mRNA
      and protein in mice but not in humans.
AB  - BACKGROUND: The R47H variant of the Triggering Receptor Expressed on Myeloid
      cells 2 (TREM2) significantly increases the risk for late onset Alzheimer's
      disease. Mouse models accurately reproducing phenotypes observed in Alzheimer'
      disease patients carrying the R47H coding variant are required to understand the
      TREM2 related dysfunctions responsible for the enhanced risk for late onset
      Alzheimer's disease. METHODS: A CRISPR/Cas9-assisted gene targeting strategy was
      used to generate Trem2 R47H knock-in mice. Trem2 mRNA and protein levels as well
      as Trem2 splicing patterns were assessed in these mice, in iPSC-derived human
      microglia-like cells, and in human brains from Alzheimer's patients carrying the
      TREM2 R47H risk factor. RESULTS: Two independent Trem2 R47H knock-in mouse models
      show reduced Trem2 mRNA and protein production. In both mouse models Trem2
      haploinsufficiency was due to atypical splicing of mouse Trem2 R47H, which
      introduced a premature stop codon. Cellular splicing assays using minigene
      constructs demonstrate that the R47H variant induced abnormal splicing only
      occurs in mice but not in humans. TREM2 mRNA levels and splicing patterns were
      both normal in iPSC-derived human microglia-like cells and patient brains with
      the TREM2 R47H variant. CONCLUSIONS: The Trem2 R47H variant activates a cryptic
      splice site that generates miss-spliced transcripts leading to Trem2
      haploinsufficiency only in mice but not in humans. Since Trem2 R47H related
      phenotypes are mouse specific and do not occur in humans, humanized TREM2 R47H
      knock-in mice should be generated to study the cellular consequences caused by
      the human TREM2 R47H coding variant. Currently described phenotypes of Trem2 R47H
      knock-in mice can therefore not be translated to humans.

PMID- 30185231
TI  - Improvements in SOD mimic AEOL-10150, a potent broad-spectrum antioxidant.
AB  - AEOL-10150 is a broad-spectrum metalloporphyrin superoxidase dismutase (SOD)
      mimic specifically designed to neutralize reactive oxygen and nitrogen species.
      Research has shown that AEOL-10150 is a potent medical countermeasure against
      national security threats including sulfur mustard (SM), nerve agent exposure and
      radiation pneumonitis following a radiological/nuclear incident sufficient to
      cause acute radiation syndrome (ARS). AEOL-10150 performed well in animal safety
      studies, and two completed phase 1 safety studies in patients demonstrated that
      the drug was safe and well tolerated, indicating that AEOL-10150 has potential as
      a new catalytic antioxidant drug. In this article, we review improvements in AEOL
      10150 in preclinical pharmacodynamic studies, especially regarding anti-SM,
      chlorine gas and radiation exposure studies.

PMID- 30185232
TI  - The lncRNA NEAT1 activates Wnt/beta-catenin signaling and promotes colorectal
      cancer progression via interacting with DDX5.
AB  - BACKGROUND: The long noncoding RNA nuclear-enriched abundant transcript 1 (NEAT1)
      has been reported to be overexpressed in colorectal cancer (CRC). However, its
      underlying mechanisms in the progression of CRC have not been well studied.
      METHODS: To investigate the clinical significance of NEAT1, we analyzed its
      expression levels in a publicly available dataset and in 71 CRC samples from
      Fudan University Shanghai Cancer Center. Functional assays, including the CCK8,
      EdU, colony formation, wound healing, and Transwell assays, were used to
      determine the oncogenic role of NEAT1 in human CRC progression. Furthermore, RNA
      pull-down, mass spectrometry, RNA immunoprecipitation, and Dual-Luciferase
      Reporter Assays were used to determine the mechanism of NEAT1 in CRC progression.
      Animal experiments were used to determine the role of NEAT1 in CRC tumorigenicity
      and metastasis in vivo. RESULTS: NEAT1 expression was significantly upregulated
      in CRC tissues compared with its expression in normal tissues. Altered NEAT1
      expression led to marked changes in proliferation, migration, and invasion of CRC
      cells both in vitro and in vivo. Mechanistically, we found that NEAT1 directly
      bound to the DDX5 protein, regulated its stability, and sequentially activated
      Wnt signaling. Our study showed that NEAT1 indirectly activated the Wnt/beta
      catenin signaling pathway via DDX5 and fulfilled its oncogenic functions in a
      DDX5-mediated manner. Clinically, concomitant NEAT1 and DDX5 protein levels
      negatively correlated with the overall survival and disease-free survival of CRC
      patients. CONCLUSIONS: Our findings indicated that NEAT1 activated Wnt signaling
      to promote colorectal cancer progression and metastasis. The NEAT1/DDX5/Wnt/beta
      catenin axis could be a potential therapeutic target of pharmacological
      strategies.

PMID- 30185233
TI  - High-resolution ISR amplicon sequencing reveals personalized oral microbiome.
AB  - BACKGROUND: Sequencing of the 16S rRNA gene has been the standard for studying
      the composition of microbial communities. While it allows identification of
      bacteria at the level of species, this method does not usually provide sufficient
      information to resolve communities at the sub-species level. Species-level
      resolution is not adequate for studies of transmission or stability or for
      exploring subspecies variation in disease association. Strain level analysis
      using whole metagenome shotgun sequencing has significant limitations that can
      make it unsuitable for large-scale studies. Achieving sufficient depth of
      sequencing can be cost-prohibitive, and even with adequate coverage,
      deconvoluting complex communities such as the oral microbiota is computationally
      very challenging. Thus, there is a need for high-resolution, yet cost-effective,
      high-throughput methods for characterizing microbial communities. RESULTS:
      Significant improvement in resolution for amplicon-based bacterial community
      analysis was achieved by combining amplicon sequencing of a high-diversity marker
      gene, the ribosomal 16-23S intergenic spacer region (ISR), with a probabilistic
      error modeling based denoising algorithm, DADA2. The resolving power of this new
      approach was compared to that of both standard and high-resolution 16S-based
      approaches using a set of longitudinal subgingival plaque samples. The ISR
      strategy resulted in a 5.2-fold increase in community resolution compared to
      reference-based 16S rRNA gene analysis and showed 100% accuracy in predicting the
      correct source of a clinical sample. Individuals' microbial communities were
      highly personalized, and although they exhibited some drift in membership and
      levels over time, that difference was always smaller than the differences between
      any two subjects, even after 1 year. The construction of an ISR database from
      publicly available genomic sequences allowed us to explore genomic variation
      within species, resulting in the identification of multiple variants of the ISR
      for most species. CONCLUSIONS: The ISR approach resulted in significantly
      improved resolution of communities and revealed a highly personalized human oral
      microbiota that was stable over 1 year. Multiple ISR types were observed for all
      species examined, demonstrating a high level of subspecies variation in the oral
      microbiota. The approach is high-throughput, high-resolution yet cost-effective,
      allowing subspecies-level community fingerprinting at a cost comparable to that
      of 16S rRNA gene amplicon sequencing. It will be useful for a range of
      applications that require high-resolution identification of organisms, including
      microbial tracking, community fingerprinting, and potentially for identification
      of virulence-associated strains.

PMID- 30185234
TI  - Increased ROS production and DNA damage in monocytes are biomarkers of aging and
      atherosclerosis.
AB  - BACKGROUND: New evidence demonstrates that aging and dyslipidemia are closely
      associated with oxidative stress, DNA damage and apoptosis in some cells and
      extravascular tissues. However, in monocytes, which are naturally involved in
      progression and/or resolution of plaque in atherosclerosis, this concurrence has
      not yet been fully investigated. In this study, we evaluated the influence of
      aging and hypercholesterolemia on serum pro-inflammatory cytokines, oxidative
      stress, DNA damage and apoptosis in monocytes from apolipoprotein E-deficient
      (apoE-/-) mice compared with age-matched wild-type C57BL/6 (WT) mice. Experiments
      were performed in young (2-months) and in old (18-months) male wild-type (WT) and
      apoE-/- mice. RESULTS: Besides the expected differences in serum lipid profile
      and plaque formation, we observed that atherosclerotic mice exhibited a
      significant increase in monocytosis and in serum levels of pro-inflammatory
      cytokines compared to WT mice. Moreover, it was observed that the overproduction
      of ROS, led to an increased DNA fragmentation and, consequently, apoptosis in
      monocytes from normocholesterolemic old mice, which was aggravated in age-matched
      atherosclerotic mice. CONCLUSIONS: In this study, we demonstrate that a pro
      inflammatory systemic status is associated with an impairment of functionality of
      monocytes during aging and that these parameters are fundamental extra-arterial
      contributors to the aggravation of atherosclerosis. The present data open new
      avenues for the development of future strategies with the purpose of treating
      atherosclerosis.

PMID- 30185237
TI  - Advancing the multi-disciplinarity of parasitology within the British Society for
      Parasitology: studies of host-parasite evolution in an ever-changing world.
AB  - The study of parasites typically crosses into other research disciplines and
      spans across diverse scales, from molecular- to populational-levels,
      notwithstanding promoting an understanding of parasites set within evolutionary
      time. Today, the 2030 Sustainable Development Goals (SDGs) help frame much of
      contemporary parasitological research, since parasites can be found in all
      ecosystems, blighting human, animal and plant health. In recognition of the multi
      disciplinary nature of parasitological research, the 2017 Autumn Symposium of the
      British Society for Parasitology was held in London to provide a forum for novel
      exchange across medical, veterinary and wildlife fields of study. Whilst the
      meeting was devoted to the topic of parasitism, it sought to foster mutualism,
      the antithesis perhaps of parasitism, by forging new academic connections and
      social networks to exchange novel ideas. The meeting also celebrated the
      longstanding career of Professor David Rollinson, FLS in the award of the
      International Federation for Tropical Medicine Medal for his efforts spanning 40
      years of parasitological research. Indeed, David has done so much to explore and
      promote the fascinating biology of parasitism, as exemplified by the 15
      manuscripts contained within this Special Issue.

PMID- 30185236
TI  - Eight years after an international workshop on myotonic dystrophy patient
      registries: case study of a global collaboration for a rare disease.
AB  - BACKGROUND: Myotonic Dystrophy is the most common form of muscular dystrophy in
      adults, affecting an estimated 10 per 100,000 people. It is a multisystemic
      disorder affecting multiple generations with increasing severity. There are
      currently no licenced therapies to reverse, slow down or cure its symptoms. In
      2009 TREAT-NMD (a global alliance with the mission of improving trial readiness
      for neuromuscular diseases) and the Marigold Foundation held a workshop of key
      opinion leaders to agree a minimal dataset for patient registries in myotonic
      dystrophy. Eight years after this workshop, we surveyed 22 registries collecting
      information on myotonic dystrophy patients to assess the proliferation and
      utility the dataset agreed in 2009. These registries represent over 10,000
      myotonic dystrophy patients worldwide (Europe, North America, Asia and Oceania).
      RESULTS: The registries use a variety of data collection methods (e.g. online
      patient surveys or clinician led) and have a variety of budgets (from being run
      by volunteers to annual budgets over ?200,000). All registries collect at least
      some of the originally agreed data items, and a number of additional items have
      been suggested in particular items on cognitive impact. CONCLUSIONS: The
      community should consider how to maximise this collective resource in future
      therapeutic programmes.

PMID- 30185239
TI  - Randomized Controlled Trial to Test the Efficacy of an Unguided Online
      Intervention with Automated Feedback for the Treatment of Insomnia.
AB  - BACKGROUND: Insomnia has become a major public health concern. AIMS: The study
      examined the efficacy of a web-based unguided self-help programme with automated
      feedback. The programme was based on cognitive behaviour therapy for insomnia
      (CBT-I). The investigation particularly focused on factors that contribute to the
      maintenance of insomnia and tested whether treatment effects were stable over a
      period of 12 months. METHOD: Fifty-six participants were randomly assigned either
      to web-based CBT-I or to the waiting-list control group. Included measures
      assessed insomnia severity, sleep-related cognitions, safety behaviours,
      depression, anxiety and somatization. In the intervention group, a sleep diary
      was used to assess sleep continuity parameters, sleep quality and daytime
      performance. RESULTS: Large between- and within-group effect sizes (d = 1.79, d =
      1.59) for insomnia severity were found. The treatment group effect remained
      stable over the period of 12 months. Further, sleep-related cognitions, safety
      behaviours, depression and somatization significantly decreased in the treatment
      group compared with the control group. On all sleep diary parameters, medium to
      large effects were revealed within the treatment group. Anxiety did not decrease
      significantly from pre- to post-assessment. For all measures except somatization
      and anxiety significant within-group effects were found at 12-month follow-up
      assessment indicating long-lasting effects. CONCLUSIONS: This study adds evidence
      to the literature on unguided online interventions for insomnia, and indicates
      that online CBT-I can have substantial long-term effects on relevant sleep
      related outcome parameters. Moreover, the results indicate that sleep-related
      cognitions and safety behaviour can be successfully altered with an unguided CBT
      I intervention.

PMID- 30185238
TI  - A pilot study using telehealth to implement antimicrobial stewardship at two
      rural Veterans Affairs medical centers.
AB  - OBJECTIVE: To test the feasibility of using telehealth to support antimicrobial
      stewardship at Veterans Affairs medical centers (VAMCs) that have limited access
      to infectious disease-trained specialists. DESIGN: A prospective quasi
      experimental pilot study. SETTING: Two rural VAMCs with acute-care and long-term
      care units.InterventionAt each intervention site, medical providers, pharmacists,
      infection preventionists, staff nurses, and off-site infectious disease
      physicians formed a videoconference antimicrobial stewardship team (VAST) that
      met weekly to discuss cases and antimicrobial stewardship-related education.
      METHODS: Descriptive measures included fidelity of implementation, number of
      cases discussed, infectious syndromes, types of recommendations, and acceptance
      rate of recommendations made by the VAST. Qualitative results stemmed from semi
      structured interviews with VAST participants at the intervention sites. RESULTS:
      Each site adapted the VAST to suit their local needs. On average, sites A and B
      discussed 3.5 and 3.1 cases per session, respectively. At site A, 98 of 140 cases
      (70%) were from the acute-care units; at site B, 59 of 119 cases (50%) were from
      the acute-care units. The most common clinical syndrome discussed was pneumonia
      or respiratory syndrome (41% and 35% for sites A and B, respectively). Providers
      implemented most VAST recommendations, with an acceptance rate of 73% (186 of 256
      recommendations) and 65% (99 of 153 recommendations) at sites A and B,
      respectively. Qualitative results based on 24 interviews revealed that
      participants valued the multidisciplinary aspects of the VAST sessions and felt
      that it improved their antimicrobial stewardship efforts and patient care.
      CONCLUSIONS: This pilot study has successfully demonstrated the feasibility of
      using telehealth to support antimicrobial stewardship at rural VAMCs with limited
      access to local infectious disease expertise.

PMID- 30185235
TI  - Novel and de novo mutations in pediatric refractory epilepsy.
AB  - Pediatric refractory epilepsy is a broad phenotypic spectrum with great genetic
      heterogeneity. Next-generation sequencing (NGS) combined with Sanger sequencing
      could help to understand the genetic diversity and underlying disease mechanisms
      in pediatric epilepsy. Here, we report sequencing results from a cohort of 172
      refractory epilepsy patients aged 0-14 years. The pathogenicity of identified
      variants was evaluated in accordance with the American College of Medical
      Genetics and Genomics (ACMG) criteria. We identified 43 pathogenic or likely
      pathogenic variants in 40 patients (23.3%). Among these variants, 74.4% mutations
      (32/43) were de novo and 60.5% mutations (26/43) were novel. Patients with onset
      age of seizures <=12 months had higher yields of deleterious variants compared to
      those with onset age of seizures > 12 months (P = 0.006). Variants in ion channel
      genes accounted for the greatest functional gene category (55.8%), with SCN1A
      coming first (16/43). 81.25% (13/16) of SCN1A mutations were de novo and 68.8%
      (11/16) were novel in Dravet syndrome. Pathogenic or likely pathogenic variants
      were found in the KCNQ2, STXBP1, SCN2A genes in Ohtahara syndrome. Novel
      deleterious variants were also found in West syndrome, Doose syndrome and glucose
      transporter type 1 deficiency syndrome patients. One de novo MECP2 mutation were
      found in a Rett syndrome patient. TSC1/TSC2 variants were found in 60% patients
      with tuberous sclerosis complex patients. Other novel mutations detected in
      unclassified epilepsy patients involve the SCN8A, CACNA1A, GABRB3, GABRA1,
      IQSEC2, TSC1, VRK2, ATP1A2, PCDH19, SLC9A6 and CHD2 genes. Our study provides
      novel insights into the genetic origins of pediatric epilepsy and represents a
      starting-point for further investigations into the molecular pathophysiology of
      pediatric epilepsy that could eventually lead to better treatments.

PMID- 30185240
TI  - Psychiatric and psycho-social characteristics of suicide completers: a
      comprehensive evaluation of psychiatric case records and postmortem findings.
AB  - OBJECTIVES: To explore the demographic, psychosocial and clinical characteristics
      of individuals known to the mental health services, who died by probable suicide
      in the West of Ireland. METHODS: Postmortem reports between January 2006 and May
      2012 detailed 153 individuals who died by probable suicide, 58 of whom attended
      the mental health services. Relevant socio-demographic and clinical data was
      extracted from individuals' lifetime case notes. RESULTS: Recurrent depressive
      disorder (44%) was the most common diagnosis and hanging the most common method
      of death (58%). Of individuals who died by hanging, 79% previously attempted
      suicide by the same method. For individuals with a documented history of
      depression, only 32% had antidepressants detected in their toxicology reports.
      Similarly, only one individual (20%) with schizophrenia had antipsychotics
      detected in their toxicology report. CONCLUSIONS: Individuals who died by
      probable suicide, most commonly died by hanging and drowning; with previous
      attempts of hanging particularly prevalent in the group who subsequently died by
      hanging. At the time of death, less than one-third of individuals according to
      toxicology reports were taking the medication that was last prescribed to them by
      the mental health services suggesting a high rate of treatment non-concordance in
      individuals who died by probable suicide.

PMID- 30185241
TI  - Are psychiatric team meetings patient centred? A cross-sectional survey on
      patient views regarding multi-disciplinary team meetings.
AB  - OBJECTIVES: The system of weekly psychiatric ward rounds is being challenged and
      multi-disciplinary team meetings (MDTMs) involving inpatients have been
      developed. These aim to improve integration between medical and social services
      and increase patient involvement in their care. However, such large meetings are
      potentially threatening to the patient. This survey aimed to examine inpatient
      experience of MDTMs and identify factors that significantly alter this
      experience. METHODS: In this cross-sectional survey we assessed patient opinion
      regarding patient inclusive MDTMs in a psychiatric inpatient unit. A total of 27
      participants (response rate 90%) were included. We utilised descriptive
      statistics and Fisher's exact test for non-parametric data where appropriate.
      RESULTS: In all, 85% (n=23) of patients identified the consultant psychiatrist as
      a member that they would like to have present at the MDTM. The ward nurse was
      identified by 63% (n=17) of patients. In all, 48% (n=13) of patients reported
      feeling anxious/threatened at the MDTM. In all, 70% (n=19) of patients stated
      that they would have felt less threatened at the MDTM if there were fewer people
      in attendance. A significant number of voluntary patients (n=11) felt
      threatened/anxious at the MDTM compared with involuntary patients (n=2) (chi
      2=4.921, df=1, p=0.026). CONCLUSION: The central findings of this study are that
      patients would prefer fewer people at the MDTM and would feel less
      threatened/anxious if they participated in selecting those in attendance. These
      findings suggest that greater patient involvement in preparation for the MDTM
      could result in a less anxiety filled experience for them.

PMID- 30185242
TI  - Occupational stress and UN peacekeepers.
AB  - BACKGROUND: Ireland has been actively involved in peacekeeping operations since
      the 1950s. The unique psychological stressors associated with this form of
      military activity have been under-recognised and under-researched. Aim The aim of
      this paper is to bring to the attention of mental health professionals, who have
      been caring for military and retired military peacekeeping personnel, the unique
      difficulties associated with peacekeeping and how they can impact upon the mental
      health of the peacekeeper. METHODS: The nature of peacekeeping is outlined. There
      is a short review of the limited literature on the mental health effects of this
      kind of military deployment. There is also an outline of the positive outcomes
      for the majority of those who have served as peacekeepers. RESULTS: Both the
      negative and the positive mental health outcomes depend on the particular
      mission. Each mission is different and the nature of a mission also changes over
      time. Post-traumatic stress disorder rates can vary from 3% to 15% of a
      peacekeeping cohort, depending upon the nature of the violence associated with
      the mission. The vast majority of peacekeepers have found their peacekeeping
      deployments as an enriching experience. CONCLUSION: Peacekeepers are often
      witnesses as well as the victims of traumatic events. The restrictions placed
      upon their military role by the mission mandate can be a source of stress for
      them. Their mental health needs to be supported during the mission and after they
      have returned home.

PMID- 30185243
TI  - Steroids, psychosis and poly-substance abuse.
AB  - OBJECTIVE: To review consequences of the changing demographic profile of anabolic
      androgenic steroid (AAS) use. METHOD: Case report and review of key papers.
      RESULTS: We report here a case of a 19-year-old Irish male presenting with both
      medical and psychiatric side effects of methandrostenolone use. The man had a
      long-standing history of harmful cannabis use, but had not experienced previous
      psychotic symptoms. Following use of methandrostenolone, he developed
      rhabdomyolysis and a psychotic episode with homicidal ideation. Discussion Non
      medical AAS use is a growing problem associated with medical, psychiatric and
      forensic risks. The population using these drugs has changed with the result of
      more frequent poly-substance misuse, potentially exacerbating these risks.
      CONCLUSION: A higher index of suspicion is needed for AAS use. Medical personnel
      need to be aware of the potential side effects of their use, including the risk
      of violence. Research is needed to establish the magnitude of the problem in
      Ireland.

PMID- 30185244
TI  - Cognitive behavioural psychotherapy graduates in Ireland: a follow-up survey of
      graduates from an Irish university.
AB  - BACKGROUND: Training in cognitive behavioural psychotherapy (CBT) is expensive
      both for the students and their funding bodies. OBJECTIVES: It is important to
      know how graduates of CBT courses are putting their skills to use, and whether
      they are continuously updating those skills to achieve best practice. We also
      wanted to discover the similarities and differences between CBT trainees in the
      United Kingdom and in the Republic of Ireland (courses in the United Kingdom
      being analogous to those in Ireland in content and participants). METHOD: An
      internet survey, derived from previous postal questionnaires, was used to enquire
      into the practice, experience, and continuing professional development of
      graduates from the CBT courses at Trinity College Dublin. RESULTS: Most MDT
      professions were represented in the graduates, preponderantly psychiatrists and
      mental health nurses, but also including social workers and occupational
      therapists. Most participants believed that the course had enhanced their
      careers, and almost half had changed job since graduating. Half said that CBT was
      now the main focus of their job, but others reported lack of resources, funding,
      time, and other duties impeded their ability to conduct CBT with clients.
      However, most participants engaged in continuous professional development
      regarding CBT, and received CBT clinical supervision. Discussion There was a
      difference in the proportion of the different professions undertaking this course
      compared with the United Kingdom and our response rate here was significantly
      lower. As in UK surveys, participants who may have been supported and funded to
      undertake the training may not afterwards be supported in implementing their
      skills in the workplace. The broader implications of this are discussed.

PMID- 30185245
TI  - Review: psychiatric and medical consequences of disordered sleep.
AB  - OBJECTIVES: The aim of this article is to draw attention to the clinical
      importance of disordered sleep in psychiatry and to demonstrate the growing
      awareness of medical illness as a complication of disordered sleep. As background
      to these main objectives, some general points are made to illustrate present-day
      approaches to the common and often serious problem of sleep disturbance. METHODS:
      The review is based on a literature search from which key publications were
      selected to illustrate, in turn, main connections between disordered sleep and
      psychiatric and medical conditions. RESULTS: Many such connections are described.
      Throughout psychiatry, regarding patients whatever their age, these connections
      have implications for clinical assessment and management. Emphasis is placed on
      the risk of misdiagnosis of sleep disorders as psychiatric or medical conditions.
      Examples of this are provided. The growing evidence that disordered sleep can
      predispose to medical illness is discussed. CONCLUSION: As the subject of sleep
      and its disorders is particular relevant in psychiatry, a working knowledge of
      modern sleep medicine is important in all branches of psychiatric and other
      medical practice as well as in clinical research.

PMID- 30185246
TI  - Standards of prescription writing in a long-term psychogeriatric unit: a series
      of clinical audits.
AB  - OBJECTIVE: The aim of this study was to improve the quality of prescription
      writing in a long-term psychogeriatric inpatient unit by a combination of serial
      audits and interventions designed to address the identified deficiencies.
      METHODS: We undertook three clinical audits of the prescription sheets used in an
      inpatient unit providing continuing care for residents with severe and enduring
      mental illness and dementia. Based on the findings of the first audit a set of
      prescribing guidelines was implemented into the ward. Following the second audit
      a new prescription sheet was developed. The format of the new prescription sheet
      was designed to account for the needs of the unit and to adhere to Irish and UK
      best practise guidelines. Two months after its introduction we undertook a third
      audit. RESULTS: Completion of the drug sensitivity box increased from 25% at
      audit one to 100% at audit three. Other specific aspects of prescription writing
      that had been poor at the beginning of the audit cycle also showed improvement:
      prescribing of generic psychotropic drugs increased by 69% and inclusion of the
      prescribers Medical Council Registration Number increased by 78%. However, some
      basic aspects of prescription writing remained weak such as frequency of drug
      administration and documentation of the stop/review date for 'as required'
      medication. CONCLUSION: The results of this study suggest that clinical audit and
      feedback can improve the quality of prescriptions in an in-patient setting.

PMID- 30185247
TI  - Revising, reforming, reframing: Report of the Expert Group on the Review of the
      Mental Health Act 2001 (2015).
AB  - Involuntary psychiatric admission and treatment in Ireland is chiefly governed by
      the Mental Health Act 2001. The Irish government announced a review of the 2001
      Act in July 2011, and the Report of the Expert Group on the Review of the Mental
      Health Act 2001 was published on 5 March 2015. The report, which constitutes
      advice to the Minister for Primary Care, Social Care (Disabilities & Older
      People) and Mental Health, presents 165 recommendations relating to virtually all
      areas of the Act. It recommends that 'insofar as practicable, a rights based
      approach should be adopted throughout any revised mental health legislation' and
      that the principle of 'best interests' should be replaced by an alternative set
      of principles as follows: 'the enjoyment of the highest attainable standard of
      mental health, with the person's own understanding of his or her mental health
      being given due respect; autonomy and self-determination; dignity (there should
      be a presumption that the patient is the person best placed to determine what
      promotes/compromises his or her own dignity); bodily integrity; and least
      restrictive care'. The Report presents a series of other recommendations aimed at
      increasing multi-disciplinary involvement in key decisions, promoting human
      rights and strengthening inspections of community facilities. Overall, the
      package of measures outlined in the Report is complex, interesting and worthy of
      debate.

PMID- 30185248
TI  - Urogenital schistosomiasis and hybridization between Schistosoma haematobium and
      Schistosoma bovis in adults living in Richard-Toll, Senegal.
AB  - Since the construction of the Diama Dam (1985), the epidemiology of
      schistosomiasis along the Senegal River Basin (SRB) has been extremely dynamic
      with outbreaks of both intestinal and urogenital schistosomiasis. In the early
      2000s, technicians reported cases of suspected urogenital schistosomiasis in
      adults from the local hospital in Richard-Toll, Lower SRB. The genetic analysis
      of schistosome miracidia isolated from 11 patients in 2012 from two
      neighbourhoods (Campement and Gaya) of Richard-Toll confirmed infection with
      Schistosoma haematobium but also S. haematobium/S. bovis hybrids. Thirty-seven
      per cent of the miracidia were S. bovis/S. haematobium hybrids and 63% were pure
      S. haematobium. The data are discussed in relation to the ongoing dynamic
      epidemiology of the schistosomes in Senegal and the need to treat non-target
      individuals.

PMID- 30185249
TI  - Trazodone and exacerbation of psychotic symptoms: an unfamiliar link.
AB  - OBJECTIVE: In this case report we attempt to emphasize the unfamiliar link
      between trazodone and relapse of psychotic symptoms. METHOD: Case report and
      literature review of relevant papers. RESULTS: We report a case of a 78-year-old
      woman with an established diagnosis of paranoid schizophrenia who has experienced
      an exacerbation of positive psychotic symptoms following initiation of 50 mg
      dailydose of trazodone. We noted that psychotic symptoms abated following
      discontinuation of trazodone. CONCLUSION: Trazodone use in patients in remission
      from schizophrenia may be associated with relapse of psychotic symptoms and
      caution is required.

PMID- 30185250
TI  - Quality of psychiatric discharge summaries: a service evaluation following the
      introduction of an electronic discharge summary system.
AB  - BACKGROUND: There has been a recent move in psychiatry towards the use of
      electronic discharge (e-discharge) summaries in an effort to improve the
      efficiency of communication between primary and secondary care, but there are
      little data on how this affects the quality of information exchanged. OBJECTIVE:
      To evaluate the quality of psychiatric discharge summaries before and after the
      introduction of the e-discharge summary system. METHODS: A retrospective analysis
      of 50 dictated discharge summaries from 1 January to 1 July 2010 and of 50 e
      discharge summaries from 1 January to 1 July 2012, evaluating for the inclusion
      of 15 key items of clinical information. RESULTS: The average total score of the
      dictated summaries (mean=9.5, s.d.=2.0) was significantly higher (p<0.001) than
      the e-discharge summaries (mean=6.7, s.d.=1.8). There were statistically
      significant differences in five of the standards: findings of physical
      examination (p<0.001), ICD-10 code (p<0.001), forensic history (p<0.001), alcohol
      history (p<0.001) and drug history (p<0.001). CONCLUSION: Our results revealed a
      decline in the quality of discharge summaries following the introduction of an
      electronic system. The reasons for this are unclear and require further analysis.
      Specific suggestions will depend on the local need, but include improvements in
      software design and layout as well as better education and training.

PMID- 30185251
TI  - Dialectical behaviour therapy for younger adults: evaluation of 22 weeks of
      community delivered dialectical behaviour therapy for females 18-25 years.
AB  - BACKGROUND: Dialectical behaviour therapy (DBT) is a multi-modal psychological
      therapy with established efficacy in treating borderline personality disorder
      (BPD). Younger adults represent a group more likely to drop out of treatment than
      their older counterparts and treatments specifically targeted at this younger
      cohort may be advantageous. The current study We describe an evaluation of a DBT
      programme in a mental health centre for younger adults 18-25 years who met
      criteria for BPD (n=11). Methodology We used a simple pre/post-test design,
      measuring BPD symptoms, general mental health symptoms, and coping skills using
      self-report questionnaires at the beginning of DBT and again following the
      delivery of 22 weeks of DBT. Findings Statistically significant reductions were
      found in BPD symptoms and several mental health symptoms alongside an increase in
      DBT skills use. Dropout was 31% at 22 weeks of treatment. Methodological
      weaknesses and avenues for future research are discussed.

PMID- 30185252
TI  - Negative outcomes in attention-deficit/hyperactivity disorder comorbid with
      oppositional defiant disorder.
AB  - OBJECTIVES: In children and adolescents diagnosed with attention
      deficit/hyperactivity disorder (ADHD), the comorbidity of the oppositional
      defiant disorder (ODD) negatively affects the course of ADHD. The purpose of this
      study was to compare ADHD-diagnosed children with and without ODD comorbidity in
      terms of smoking, psychoactive substance use, disciplinary punishments at school,
      criminal behaviors, and unintentional injuries. METHODS: This study included 109
      children diagnosed with ADHD alone and 79 children with the ADHD-ODD comorbidity
      from a child psychiatry outpatient clinic. The children who participated in the
      study were aged between 6 and 15 years. Diagnoses of the children were determined
      by child psychiatrists according to DSM-IV criteria, and the Turgay DSM-IV-based
      Child and Adolescent Behavior Disorders Screening and Rating Scale-Parents Form
      was used to support the diagnosis in initial evaluations of children. Forty-six
      to fifty months after the first admission, parents were questioned regarding all
      negative outcomes from the time of first diagnosis to the time of the evaluation
      by phone. RESULTS: The groups were compared in terms of smoking, psychoactive
      substance use, disciplinary punishments at school, criminal behaviors, and
      unintentional injuries over a period of 4 years. The ODD-ADHD group was
      determined to have higher rates of disciplinary punishments at school, smoking,
      and unintentional injuries compared with the ADHD group. No statistically
      significant difference was found between the two groups in terms of criminal
      behaviors and psychoactive substance use. CONCLUSIONS: The ODD comorbidity
      increases the risk of negative outcomes in children diagnosed with ADHD.

PMID- 30185253
TI  - The impact of a change in prescribing policy on antipsychotic prescribing in a
      general adult psychiatric hospital.

PMID- 30185254
TI  - An evaluation of a group-based motivational intervention for substance misusers
      in an Irish forensic setting.
AB  - OBJECTIVE: The purpose of this pilot study was to evaluate a 12-session group
      based motivational intervention for substance misusers in a prison setting. The
      intervention aimed to increase both participants awareness of problem substance
      use and motivation to change their substance use behaviour. METHOD: Participants
      were recruited for the intervention through active outreach in the prison.
      Participants of the intervention group completed a structured interview before
      the group commencing and standardised pre- and post-outcome measures. The results
      of the intervention group (n=31) were compared with a waiting list control group
      (n=11). RESULTS: Non-parametric analysis showed retention rates on this programme
      at 2, 4 and 6 weeks were 88%, 79% and 76%, respectively. Outcome data were
      consistent with the predicted direction for the treatment group compared with the
      wait-list control with significant between-group differences found on ambivalence
      and taking steps scores. CONCLUSION: This group-based intervention demonstrated
      positive levels of client engagement and retention. The intervention was also
      successful in reducing participant ambivalence about their drug use. Implications
      for service provision are discussed and design limitations of the present study
      are considered. Overall, findings indicate the potential utility of a group-based
      motivational intervention for substance misusers in forensic settings.

PMID- 30185255
TI  - The impact of a change in prescribing policy on antipsychotic prescribing in a
      general adult psychiatric hospital.

PMID- 30185256
TI  - Rate of involuntary admission in Dublin South West: a 5-year retrospective
      review.
AB  - OBJECTIVE: International figures for involuntary admissions vary widely.
      Differences in legislation, professionals' ethics and public attitudes towards
      risk have been known to influence this rate. Comparing involuntary admission
      rates in different parts of the same country can help control for variability
      found between international studies. This study assessed the rates of involuntary
      admissions in the Dublin South West Mental Health Service compared with the rest
      of Ireland. METHODS: We examined the demographic and clinical profiles of all
      involuntary patients admitted to the acute psychiatric inpatient unit in Tallaght
      Hospital between 2007 and 2011. We compared the rate of admission in Tallaght
      with the rest of Ireland. Data gathered included all patients detained on Form 6
      and Form 13 (change of status) looking at age, gender, diagnosis and number of
      patients who had a Mental Health Tribunal. Form 7 (renewal orders) was also
      examined We calculated the rate per 100 000 population per year of Form 6
      admissions, Form 13 and Form 7 (certificate and renewal order by responsible
      consultant psychiatrist) using figures from the 2006 Census. All data were
      analysed using SPSS. RESULTS: The rate of involuntary admission in Tallaght
      Hospital was significantly lower compared with the rest of Ireland (Form 6: t=
      11.2; p<0.001, Form 13: t=-3.1; p=0.04, Form 7: t=-13.9; p=0.001). This
      difference was evident for all methods of involuntary detention and was also the
      case for Form 7 (renewal orders). Mental Health Tribunals were held for 59% of
      patients, a rate comparable with earlier findings described in publications,
      following the introduction of the new Mental Health Act. CONCLUSIONS: Rates per
      100 000 population were lower in Dublin South West compared with the rest of
      Ireland. The reasons for this are not clear. Further research comparing similar
      services in Ireland could explain these findings.

PMID- 30185257
TI  - Increased use of security personnel in Irish psychiatric hospitals: 2008-2012.
AB  - OBJECTIVES: Little is known about the involvement of security personnel in Irish
      psychiatric care. Content analysis of inspection reports is a feasible way to
      investigate this under-researched topic. We aimed to (i) Describe the number of
      approved centres per year in which we observed comments about the presence of
      security personnel in published reports of inspections conducted from 2008 to
      2012 (ii) Report the main themes of all text relating to security personnel
      published in these inspection reports. METHOD: We conducted a content analysis of
      all 349 inspection reports published between 2008 and 2012. RESULTS: The number
      of approved centres in which security personnel were noted increased from 3% to
      8% between the years 2008 and 2012. This increase was not statistically
      significant when the same unique centres were compared between years (p=0.684).
      Employment details such as contracted employment relationship, location relative
      to the approved centre and hours of work appeared inconsistent across centres.
      Role functions of security personnel differed across centres and ranged from
      monitoring the entrance of a unit to observing, restraining and secluding
      patients. Contrasting perceptions of suitability were evident in the inspection
      reports. The extent to which the training needs of security personnel were met
      was unclear from the reports. CONCLUSIONS: Activity of security personnel in
      psychiatric hospitals may not be role appropriate, compliant with legislation or
      conducive to treatment. Best practice guidelines should be developed in
      consultation with multiple stakeholders.

PMID- 30185258
TI  - Letter to the Editor.

PMID- 30185259
TI  - Reply.

PMID- 30185260
TI  - Letter to the Editor.

PMID- 30185261
TI  - Review: psychiatric and medical consequences of disordered sleep - Corrigendum.

PMID- 30185262
TI  - Review of clinical guidelines for children and adolescents with attention deficit
      hyperactivity disorder and their application to an Irish context.
AB  - BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is a
      neurodevelopmental disorder with international prevalence rates estimated to be
      5%. It is currently the most common disorder treated in Child and Adolescent
      Mental Health Services in Ireland. There have been a number of guidelines
      worldwide produced to aid clinicians in the diagnosis and treatment of ADHD;
      however, there are no guidelines available specifically for the Irish population
      and healthcare system. OBJECTIVES: The aim of this paper is to review the
      available clinical guidelines for the diagnosis and management of ADHD in
      children adolescents across North America, Canada, Europe and the United Kingdom
      and to apply these to an Irish context. METHODS: A number of international
      guidelines were reviewed. A proposed pathway for the assessment and treatment of
      children and adolescents with ADHD has been devised with the recommendation that
      a formalised consensus guideline should be implemented. CONCLUSION: This review
      paper has highlighted that there is consensus between the guidelines for the
      diagnosis of ADHD with a thorough clinical history remaining the gold standard.
      They further agree on the importance of identifying co-morbid disorders. When it
      comes to the treatment, the guidelines are less unified. This current paper has
      devised a proposed care pathway for ADHD in Ireland to ensure high quality cost
      effective care within its healthcare system.

PMID- 30185263
TI  - Computerised cognitive behavioural therapy for alcohol use disorder: a pilot
      randomised control trial.
AB  - BACKGROUND: Cognitive behavioural therapy (CBT) has been used in the treatment of
      alcohol use disorder (AUD), generally in individual or group therapy, but not via
      computer. Aim This study examined the effectiveness of an interactive,
      personalised, computer-based CBT therapy in a randomised control trial. METHODS:
      We studied a group of 55 patients with AUD, randomised to either 5-hour-long
      computerised CBT sessions or a placebo cognitive-stimulating session, together
      with a 4-week inpatient rehabilitation treatment, and followed them for 3 months.
      RESULTS: There was a high degree of patient adherence to the protocol. Both
      groups did well, with a significant fall in alcohol outcome measures including
      number of drinks per drinking day, and number of drinking days, and an increase
      in abstinence rates in both groups to an equivalent level. The CBT group attended
      alcoholics anonymous groups more frequently, and had significant alterations in
      their alcohol self-efficacy outcomes, which correlated with their drinking
      outcomes. We concluded that computerised CBT is a potentially useful clinical
      tool that warrants further investigation in different treatment settings for AUD.

PMID- 30185264
TI  - Young people in drug treatment in Ireland: their views on substance use
      aetiology, trajectory, parents' role in substance use and coping skills.
AB  - OBJECTIVES: The aim of the current study was to gain insight into the process of
      initiation and progression to problematic use among young people who reach
      clinically significant levels of substance use requiring treatment. METHOD:
      Twenty young people, aged between 15 and 19 years from two different drug
      treatment centres in Ireland were interviewed regarding their views on their
      pathway into substance use, their progress to more problematic use, their
      perception of their parents' role, if any, in their trajectory and their typical
      coping style before treatment. Content analysis was conducted on the resulting
      narratives. RESULTS: The use of substances to cope with life stressors emerged as
      a prominent theme at initial and problematic stages of use. Multiple maladaptive
      coping approaches were reported. Both direct and indirect influences from parents
      in their substance use problem were cited. However, some participants reported
      that parents had no causal role in their substance use trajectory, in particular
      regarding mothers. CONCLUSIONS: The current findings suggest that substance
      misuse is a multi-determined problem and a number of intervention strategies are
      suggested to delay onset and related harms associated with adolescent substance
      use.

PMID- 30185265
TI  - Mindfulness-based cognitive therapy for psycho-oncology patients: an exploratory
      study.
AB  - OBJECTIVES: Mindfulness-based cognitive therapy (MBCT) is a group-based
      intervention similar to mindfulness-based stress reduction, but which includes
      cognitive therapy techniques. This study investigates its usefulness in the
      treatment of depressive, anxiety and stress/distress symptoms in cancer patients
      referred to a psycho-oncology service. It also examines whether effect on
      depression is mediated by self-compassion. METHOD: In phase 1 of this study, 16
      cancer patients with mild/moderate psychological distress were randomised to MBCT
      (n=8) or treatment as usual (TAU; n=8), and assessed pre- and post-treatment.
      Analysis of variance was performed to examine the effect of treatment on anxiety
      and depression. In phase 2, the TAU group received the intervention, and results
      of pre- and post-MBCT assessments were combined with those receiving MBCT in
      phase 1. Finally, both groups were followed up at 3 months. RESULTS: In phase 1,
      the MBCT group had a significant improvement in mindfulness and a decrease in
      anxiety. Statistically significant improvements in both depression and anxiety
      were found at 3 month follow-up. Self-compassion appeared to mediate the effect
      on anxiety/depression. CONCLUSION: This small pilot study suggests that MBCT may
      have a beneficial effect on psychological variables often adversely affected in
      cancer in a heterogeneous cancer population.

PMID- 30185266
TI  - A pilot music group for young people attending a community Child and Adolescent
      Mental Health Service.
AB  - OBJECTIVE: There is a strong and growing body of evidence supporting the mental
      health benefits of music. With regard to Child and Adolescent Mental Health
      Services (CAMHS) there is a need for creative, child friendly approaches to
      improve rapport and promote engagement. This study was established as an
      exploratory pilot project to assess the feasibility of a running a music group
      within a CAMHS setting as well as any potential benefit to the mental health of a
      group of diagnostically heterogeneous young people attending the service.
      METHODS: Five young people attending the out-patient clinic participated in a
      weekly music group over the course of 2 months. Feedback was obtained using a
      study specific questionnaire as well as baseline and follow-up Strengths and
      Difficulties Questionnaires. RESULTS: The music group was described as an
      enjoyable experience in the clinic setting and young people identified benefits
      with regard to mood, self-confidence and social skills. Attendance at
      appointments within the clinic was good for the duration of the group, suggesting
      a benefit in encouraging engagement. CONCLUSIONS: A music group is a welcome
      intervention in a CAMHS setting with potential positive benefits for both the
      service and service users. Further work is needed to establish specific mental
      health benefits of music-based interventions in young people with mental health
      difficulties.

PMID- 30185267
TI  - Inpatient suicide death in Ireland: challenges and opportunities for clinical
      care.
AB  - Rates of admissions and residency in Irish psychiatric units and hospitals have
      decreased significantly over the last 30 years. Through this period national
      suicide rates have increased, with Ireland currently having the 17th highest
      suicide rate of the 27 EU countries and the fourth highest rate in males aged 15
      24 years. Suicide deaths among inpatients in psychiatric care are rare but tragic
      occurrences. At present, little is known about the incidence, prevalence or
      profile of inpatient suicide in Ireland and in comparison with other European
      countries. Addressing a similar deficit, the United Kingdom established a
      National Confidential Enquiry in 1992, which over the past two decades has used a
      standardized research methodology to comprehensively investigate all suicide
      deaths of, and homicides committed by, people in contact with the mental health
      services. This inquiry, using a no-fault and confidential approach with all
      clinicians has informed and improved services and policies and possibly impacted
      on suicide reduction efforts in the United Kingdom. Suicide prevention efforts in
      Ireland are negatively influenced by an ongoing stigma of mental illness and
      suicide, which sustains the knowledge gap in relation to inpatient suicide. A
      similar method of enquiry to that of the UK confidential approach blended with
      current demographic and clinical data sources and including family input (from
      those bereaved by inpatient suicide) could inform a tailored policy and provide a
      valuable model for studying suicide across all inpatient and community
      psychiatric services.

PMID- 30185268
TI  - Intervening early in bipolar disorder in young people: a review of the clinical
      staging model.
AB  - Bipolar disorder (BPD) essentially has its onset during adolescence and early
      adulthood. It has the capacity to be highly disruptive, dislocating individuals
      from their normal developmental trajectory and potentially causing significant
      long-term co-morbidity and chronicity. At a societal level the burden created is
      greater than schizophrenia. This is not helped by the very substantial delays in
      its diagnosis and appropriate treatment. Thus, there is a clear rationale for
      intervening earlier and at a younger age. However, the field of early
      intervention in BPD is in its infancy. One approach that conceptually provides a
      basis for early intervention is the Clinical Staging Model (used widely in
      general medicine). This article outlines how this model helps in an understanding
      of the emerging stages of BPD. It also summarises the interventions that might be
      appropriately introduced if a person progresses from an early to a late stage of
      the illness. Early intervention has a well-established record in psychotic
      disorders. If it can be realised for BPDs, then it may hold out hope of better
      outcomes for the next generation of young people at risk.

PMID- 30185269
TI  - Arguments for transformational reform of mental health care for young people.

PMID- 30185270
TI  - Youth mental health in Ireland: a lot done, more to do?
AB  - The emergence of a new youth mental health paradigm has challenged how we think
      about the provision of mental health care for adolescents and young adults. This
      editorial tracks the origins of this new paradigm within the field of mental
      health both internationally and in Ireland.

PMID- 30185271
TI  - How social context impacts on the development, identification and treatment of
      mental and substance use disorders among young people - a qualitative study of
      health care workers.
AB  - : Introduction Social context has a major influence on the detection and
      treatment of youth mental and substance use disorders in socioeconomically
      disadvantaged urban areas, particularly where gang culture, community violence,
      normalisation of drug use and repetitive maladaptive family structures prevail.
      This paper aims to examine how social context influences the development,
      identification and treatment of youth mental and substance use disorders in
      socioeconomically disadvantaged urban areas from the perspectives of health care
      workers. METHOD: Semi-structured interviews were conducted with health care
      workers (n=37) from clinical settings including: primary care, secondary care and
      community agencies and analysed thematically using Bronfenbrenner's Ecological
      Theory to guide analysis. RESULTS: Health care workers' engagement with young
      people was influenced by the multilevel ecological systems within the
      individual's social context which included: the young person's immediate
      environment/'microsystem' (e.g., family relationships), personal relationships in
      the 'mesosystem' (e.g., peer and school relationships), external factors in the
      young person's local area context/'exosystem' (e.g., drug culture and
      criminality) and wider societal aspects in the 'macrosystem' (e.g., mental health
      policy, health care inequalities and stigma). CONCLUSIONS: In socioeconomically
      disadvantaged urban areas, social context, specifically the micro-, meso-, exo-,
      and macro-system impact both on the young person's experience of mental health or
      substance use problems and services, which endeavour to address these problems.
      Interventions that effectively identify and treat these problems should reflect
      the additional challenges posed by such settings.

PMID- 30185272
TI  - Development and evaluation of an educational intervention in youth mental health
      for primary care practitioners.
AB  - OBJECTIVES: Irish adolescents have one of the highest rates of suicide and self
      harm in the European Union. Although primary care has been identified as an
      opportune environment in which to detect and treat mental health problems in
      adolescents, lack of training among primary care professionals (PCPs) is a
      barrier to optimum identification and treatment. We describe the development and
      evaluation of an educational intervention on youth mental health and substance
      misuse for PCPs. METHODS: Thirty general practitioners and other PCPs working in
      the Mid-West region participated in an educational session on youth-friendly
      consultations, and identification and treatment of mental ill-health and
      substance use. Learning objectives were addressed through a presentation, video
      demonstration, small group discussions, role play, question-and-answer sessions
      with clinical experts, and an information pack. Following the session,
      participants completed an evaluation form assessing knowledge gain and usefulness
      of different components of the session. RESULTS: A total of 71% of participants
      were involved in the provision of care to young people and 55% had no previous
      training in youth mental health or substance abuse. Participants rated knowledge
      gains as highest with regard to understanding the importance of early
      intervention, and primary care, in youth mental health. The components rated as
      most useful were case studies/small group discussion, the 'question-and-answer
      session' with clinical experts, and peer interaction. CONCLUSIONS: The
      educational session outlined in this pilot was feasible and acceptable and may
      represent an effective way to train professionals to help tackle the current
      crisis in youth mental health.

PMID- 30185273
TI  - Youth services: meeting the mental health needs of adolescents.
AB  - OBJECTIVES: Youth mental health services are poised for a paradigm shift. Recent
      epidemiological evidence confirms the seriousness of adolescence as a risk period
      for mental ill-health - 50% of all adult mental disorders begin before the age of
      16% and 75% before the age of 25. Here, we identify issues with transition of
      care between CAMHS-AMHS service, and effectiveness of early intervention
      services. METHODS: We provide a selective review providing evidence of
      adolescence as a risk period, discuss CAMHS-AMHS service transition problems, and
      discuss avenues for change to implement the early intervention model across youth
      mental health. RESULTS: Traditional service structures,with paediatric -adult
      split at 16-18 years increasingly appear not fit for purpose. A radical redesign
      of youth mental health services is not only necessary, it is also feasible and
      achievable, as illustrated by a pilot Birmingham youth service - Youthspace.
      CONCLUSIONS: Pilot youth mental projects currently underway can help radically
      redesign the existing child and adolescent services. This will in turn lead to an
      improvement in the young people's experience of engagement with the services so
      that they too have a positive future.

PMID- 30185274
TI  - Childhood trauma and functional disability in psychosis, bipolar disorder and
      borderline personality disorder: a review of the literature.
AB  - OBJECTIVES: We aimed to examine the association between childhood trauma and
      functional impairment in psychotic disorders, bipolar disorder and borderline
      personality disorder, to speculate on possible mechanisms that underlie this
      association and discuss the implications for clinical work. METHODS: Narrative
      review of the peer-reviewed English language literature in the area. RESULTS:
      High rates of childhood trauma in psychotic disorders, bipolar disorder and
      borderline personality disorder were identified. This was associated with
      impaired social and occupational functioning in both the premorbid and
      established phases of each of these psychiatric disorders over and above the
      deficits typically observed in these populations. Possible mechanisms mediating
      this relationship include neurocognitive deficits, insecure attachment, higher
      rates of comorbidities and problems with adherence and response to treatment.
      CONCLUSIONS: Routine clinical inquiry about childhood maltreatment should be
      adopted within mental health settings. This has potentially important treatment
      implications for identifying those individuals at elevated risk of functional
      disability. While there is no clear guidance currently available on how to target
      childhood trauma in the treatment of psychotic disorders, bipolar disorder or
      borderline personality disorder, there are several promising lines of enquiry and
      further research is warranted.

PMID- 30185275
TI  - Illness characteristics and symptoms in an Irish early intervention for psychosis
      service.
AB  - OBJECTIVES: Study of illness characteristics and symptoms in a young population
      with psychosis can assist for understanding of their needs, and can inform
      service planning strategies. The aims of the current study were to describe
      illness characteristics and symptoms of a first episode psychosis (FEP) sample
      aged 25 years and under, and compare with a sample aged over 25 years. METHODS:
      Interviews were conducted for 437 individuals aged 16-65 years presenting with
      suspected psychosis between 2005 and 2012 in a defined catchment area (population
      of 390 000) using the Structured Clinical Interview for DSM IV to determine the
      presence of a psychosis diagnosis. Individuals with confirmed psychosis were
      assessed using standardised instruments to determine illness characteristics at
      first presentation. RESULTS: Among the 25 years, and under FEP sample, 23.9% had
      their first onset of symptoms (prodromal or psychotic) before 18 years of age.
      After controlling for confounders, the sample aged 25 years and under had a
      significantly shorter log transformed duration of untreated psychosis (p=0.002),
      more negative symptoms (p=0.045) and greater frequency of comorbid cannabis abuse
      diagnosis (p=0.027). CONCLUSIONS: Symptom onset in a youth FEP sample frequently
      occurs before age 18 years. Certain illness characteristics differed across the
      age categories, such as greater negative symptoms and cannabis abuse in the youth
      sample. Overall, the findings support the provision of adequate strategies for
      management of negative symptom deficits and substance abuse across all ages in
      FEP.

PMID- 30185276
TI  - All of us? An exploration of the concept of mental health literacy based on young
      people's responses to fictional mental health vignettes.
AB  - OBJECTIVES: Mental health literacy is increasingly referenced as a goal of mental
      health policy. However, the current definition of this concept has a relatively
      narrow focus on mental disorders. The objectives of this study were to explore
      mental health literacy through the use of vignettes and to begin to articulate a
      broader definition. METHODS: Six groups of young people (n=42) aged between 16
      and 25 years old responded to open-ended questions about vignettes depicting
      fictional characters with diagnosable mental health problems. The responses were
      analysed using Foucault's governmentality theory. RESULTS: The responses to the
      vignettes highlighted a range of determinants of our mental health. The young
      people suggested informal mental health-promoting techniques and highlighted the
      importance of talking. Ambiguity was reported in relation to the types of
      knowledge that are important in responding to mental health need. Finally, the
      responses were reflective of young people who are empathetic and view mental
      health from the perspective of our shared humanity, rather than as a marginal
      issue. CONCLUSIONS: As mental health literacy is increasingly becoming a goal of
      mental health policy, it is timely that a shared understanding of this important
      concept is articulated. The current definition of mental health literacy is
      narrow in its focus on the recognition of mental disorders. A more broad-based
      definition of mental health literacy should be adopted by policy makers,
      reflecting the full range of determinants of mental health and recognising the
      importance of mental wellbeing.

PMID- 30185277
TI  - The risk and protective factors associated with depression and anxiety in a
      national sample of Irish adolescents.
AB  - OBJECTIVES: The aim of this study is to examine the risk and protective factors
      associated with anxiety and depression in a representative sample of Irish
      adolescents. METHODS: Data used in this study were drawn from a subset of the My
      World Survey (MWS). The MWS-Second Level (MWS-SL) subset consists of a randomised
      sample of 72 schools, with a final sample of 6085 students. Outcome measures were
      depression and anxiety. Risk and protective factors included measures within the
      socio-demographic, psychosocial and risk-taking domains. RESULTS: One in three
      adolescents experienced elevated levels of depression and anxiety. Age, gender,
      maternal education, family composition, parental mental health as well as the
      experience of racism and bereavement were associated with elevated distress.
      Psychosocial factors associated with depression and anxiety included optimism,
      personal competence, life-satisfaction, self-esteem, anger, body dissatisfaction,
      family competence, maternal and paternal criticism, experiencing the break-up of
      a romantic relationship, school and peer connectedness as well as the
      availability of one good adult. Finally, engaging in substance misuse was found
      to increase the likelihood of anxiety and depression. CONCLUSION: Since factors
      protecting and putting adolescents at risk of anxiety and depression exist at
      every level of the adolescent's ecological system, the study supports a community
      based approach to youth mental health.

PMID- 30185278
TI  - The association between economic inactivity and mental health among young people:
      a longitudinal study of young adults who are not in employment, education or
      training.
AB  - OBJECTIVES: Increasing rates of young people not in education, employment or
      training (NEETs) are a cause of concern both in Ireland and internationally, but
      little longitudinal research has examined the link between psychiatric disorder
      in young people and NEET status. METHODS: The Challenging Times (CT) Study is a
      longitudinal, population-based study of psychopathology among 212 young Irish
      people. Clinical interviews were performed at two time points: 12-15 years and 19
      24 years. RESULTS: NEET status in young adulthood was associated with a sevenfold
      increased risk of current suicidal ideation. This result was independent of prior
      adolescent mental disorder. NEET young people had a fourfold increased odds of
      being diagnosed with a mental disorder in childhood or early adolescence compared
      with their economically active peers. NEET young people were at an almost
      threefold increased risk of any mental health disorder a twofold increased risk
      of anxiety disorder and threefold increased odds of suicide attempts over their
      lifetime compared with economically active peers. CONCLUSIONS: NEET young people
      are at increased risk for mental disorder and suicidal ideation. The association
      is bidirectional, as prior mental disorder in adolescence appeared to account for
      much of the association between NEET status and current mental health problems.
      However, economic inactivity conveys an increased risk for suicidal ideation over
      and above that due to prior disorder. Our findings provide a compelling economic
      and societal argument for early intervention and treatment of mental disorder and
      the importance of vocational interventions for reducing suicide risk in young
      adults.

PMID- 30185279
TI  - Description and outcome evaluation of Jigsaw: an emergent Irish mental health
      early intervention programme for young people.
AB  - OBJECTIVES: Jigsaw is an early intervention mental health service developed by
      Headstrong which provides support to young people, aged 12-25 years, in 10
      communities across Ireland. This study aimed to profile young people who availed
      of Jigsaw, in one calendar year, and to provide evidence that Jigsaw's model
      facilitates the reduction of psychological distress. METHODS: Participants were
      2420 young people who received support, directly or indirectly, from Jigsaw.
      Demographic details, including age, gender, presenting issues and referral
      pathways, captured on the Jigsaw Data System were described and psychological
      distress was assessed using the Clinical Outcomes in Routine Evaluation (CORE)
      questionnaires. RESULTS: A gender balance was almost observed and the majority of
      participants were between 15 and 17 years old. The most common presenting issue
      was anxiety and the most common referral sources were self, parent, general
      practitioner, school and Adult Mental Health Services (AMHS). Participants
      reported high levels of psychological distress pre-intervention and levels were
      significantly lower post intervention. CONCLUSIONS: Although a lack of control
      group limits interpretation of the study findings, this study provides emerging
      evidence that Jigsaw is an accessible and effective service which plays a key
      role in the continuum of mental health care for young people in Ireland.

PMID- 30185280
TI  - The association between parental and adolescent substance misuse: findings from
      the Irish CASE study.
AB  - BACKGROUND: Self-report data from 2716 adolescents aged 15-17 years old in Irish
      schools were analysed to consider the association between psycho-social factors
      and the presence of adolescent substance and alcohol abuse, with an emphasis on
      family circumstances. METHODS: Data were collected using the 'Lifestyle and
      Coping Questionnaire' which includes questions about lifestyle, coping, problems,
      alcohol and drug use, deliberate self-harm, depression, anxiety, impulsivity and
      self-esteem. Two additional questions were added to the standard questionnaire
      regarding parental substance misuse. RESULTS: Adolescent substance abuse was more
      common in boys; parental substance misuse increased the risk of adolescent abuse
      of alcohol and drugs; the increased risk was marginally higher if the parental
      substance abuse was maternal rather than paternal; the increased risk was higher
      if the parental substance abuse affected both rather than one of the parents,
      especially regarding adolescent drug abuse; the magnitude of the increased risk
      was similar for boys and girls. Parental substance misuse increased the risk of
      adolescent substance abuse even after adjusting for other family problems and the
      adolescent's psychological characteristics. CONCLUSIONS: This study indicates
      that parental substance misuse affects the development of both alcohol and drug
      misuse in adolescent children independent of other family problems and the
      psychological characteristics of the adolescent. A wider perspective is needed,
      including societal and family issues, especially parental behaviour, when
      attempting to reduce risk of adolescent addiction. The impact on children of
      parental substance misuse also needs consideration in clinical contexts.

PMID- 30185281
TI  - Prevalence of Mental Disorder among young adults in Ireland: a population based
      study.
AB  - BACKGROUND: There is a lack of epidemiological research on the mental health of
      young adults in Ireland. OBJECTIVES: To determine prevalence of psychiatric
      disorders in a cohort of young Irish adults. METHODS: The Challenging Times study
      was a landmark study of the prevalence of psychiatric disorders in adolescents in
      North Dublin, Ireland: 212 school children aged 12-15 years were recruited
      through schools and interviewed using the K-SADS semi-structured diagnostic
      instrument. This cohort was traced again at age 19-24 years (mean age 20.8 years)
      and interviewed using SCID I & II. Main outcome measures were current and
      lifetime Axis I and Axis II psychiatric disorders. RESULTS: Follow-up rate was
      80%. Using a weighted population prevalence analysis 19.8% of the cohort had a
      current mental disorder, 56.0% had a lifetime mental disorder of whom 28.4% had
      mood disorders, 27.1% had anxiety disorders, 22.7% had substance use disorders;
      25.4% had lifetime multi-morbidity. Cluster A personality disorders were found in
      2.3%. Lifetime prevalence of binge-drinking was 75.0%, cannabis use 65% and 17%
      of young adults had fulfilled criteria for an alcohol use disorder at sometime in
      their life. Lifetime prevalence of suicidal thoughts/behaviour was 21.1%.
      CONCLUSIONS: Lifetime prevalence of psychiatric disorder and substance use were
      high in this sample of young Irish adults. Mental Health service provision for
      this age group is a priority. Larger studies of nationally representative samples
      are needed to inform service development.

PMID- 30185282
TI  - A special issue: highlighting the youth mental health agenda.
AB  - With previous studies finding that much mental health morbidity has initial onset
      in young people, the Youth Mental Health agenda has gained momentum in recent
      times. Reform and investment in this area is now needed to address the major
      challenge of delivering age appropriate services tailored to the needs of youth.
      In this special issue the mental health of young people is brought into focus and
      some of the issues facing quality service delivery are described. This editorial
      summarises these contributions which will inform the ongoing development of this
      emerging area.

PMID- 30185283
TI  - Who is in the transition gap? Transition from CAMHS to AMHS in the Republic of
      Ireland.
AB  - OBJECTIVE: The ITRACK study explored the process and predictors of transition
      between Child and Adolescent Mental Health Services (CAMHS) and Adult Mental
      Health Services (AMHS) in the Republic of Ireland. METHOD: Following ethical
      approval, clinicians in each of Ireland's four Health Service Executive (HSE)
      areas were contacted, informed about the study and were invited to participate.
      Clinicians identified all cases who had reached the transition boundary (i.e.
      upper age limit for that CAMHS team) between January and December 2010. Data were
      collected on clinical and socio-demographic details and factors that informed the
      decision to refer or not refer to the AMHS, and case notes were scrutinised to
      ascertain the extent of information exchanged between services during transition.
      RESULTS: A total of 62 service users were identified as having crossed the
      transition boundary from nine CAMHS [HSE Dublin Mid-Leinster (n=40, 66%), HSE
      South (n=18, 30%), HSE West (n=2, 3%), HSE Dublin North (n=1, 2%)]. The most
      common diagnoses were attention deficit hyperactivity disorder (ADHD; n=19, 32%),
      mood disorders (n=16, 27%), psychosis (n=6, 10%) and eating disorders (n=5, 8%).
      Forty-seven (76%) of those identified were perceived by the CAMHS clinician to
      have an 'on-going mental health service need', and of these 15 (32%) were
      referred, 11 (23%) young people refused and 21 (45%) were not referred, with the
      majority (12, 57%) continuing with the CAMHS for more than a year beyond the
      transition boundary. Young people with psychosis were more likely to be referred
      [chi 2 (2, 46)=8.96, p=0.02], and those with ADHD were less likely to be referred
      [chi 2 (2, 45)=8.89, p=0.01]. Being prescribed medication was not associated with
      referral [chi 2 (2, 45)=4.515, p=0.11]. In referred cases (n=15), there was
      documented evidence of consent in two cases (13.3%), inferred in another four
      (26.7%) and documented preparation for transition in eight (53.3%). Excellent
      written communication (100%) was not supported by face-to-face planning meetings
      (n=2, 13.3%), joint appointments (n=1, 6.7%) or telephone conversations (n=1,
      6.7%) between corresponding clinicians. CONCLUSIONS: Despite perceived on-going
      mental health (MH) service need, many young people are not being referred or are
      refusing referral to the AMHS, with those with ADHD being the most affected.
      CAMHS continue to offer on-going care past the transition boundary, which has
      resource implications. Further qualitative research is warranted to understand,
      in spite of perceived MH service need, the reason for non-referral by the CAMHS
      clinicians and refusal by the young person.

PMID- 30185285
TI  - Breeding Characteristics and Dose-dependent Blood Pressure Responses of
      Transgenic Cyp1a1-Ren2 Rats.
AB  - Hypertension is a leading risk factor for cardiovascular and chronic kidney
      disease. A new rodent model (transgenic male Cyp1a1-Ren2 rats) provides
      reversible induction of hypertension through the addition of indole-3-carbinol
      (I3C) to the diet, without the need for surgical intervention, thus giving
      researchers control over both the onset of hypertension and its magnitude (I3C
      dose-dependency). We here report the breeding performance and productivity of
      Cyp1a1-Ren2 rats. Despite being transgenic, these animals proved to be efficient
      breeders. In addition to confirming inducible and reversible dose-dependent
      hypertension (by using I3C doses of 0.125%, 0.167%, and 0.25% [w/w] in the diet
      for 14 d, followed by normal chow for 4 d), we demonstrated that hypertension can
      be sustained chronically (14 wk) by continuous dosing with I3C (0.167% [w/w]) in
      the diet. In chronically dosed male rats, systolic blood pressure continued to
      rise, from 173 +/- 11 mm Hg after 1 mo to 196 +/- 19 mm Hg after 3 mo, with no
      adverse phenotypic features observed. In conclusion, Cyp1a1-Ren2 rats are a
      useful animal model to investigate hypertension-induced end-organ damage and
      potential new therapeutic targets to manage hypertension.

PMID- 30185287
TI  - Can You Hear Me Now?

PMID- 30185284
TI  - Ivermectin-compounded Feed Compared with Topical Moxidectin-Imidacloprid for
      Eradication of Demodex musculi in Laboratory Mice.
AB  - Demodex musculi is a prostigmatid follicular mite that has rarely been reported
      in laboratory mice. Although prevalence of this species has not been assessed
      formally, we have found that many imported mouse strains from noncommercial
      sources harbor Demodex mites. To assess whether an acaricide can be used to
      eradicate this mite, infested immunocompromised mice were provided ivermectin
      compounded (12 ppm) feed without restriction for 8 wk (n = 10), were treated
      topically with moxidectin and imidacloprid (MI; 3 and 13 mg/kg, respectively)
      weekly for 8 wk (n = 10), or remained untreated (n = 10). Mice were confirmed to
      be mite-infested before treatment and were tested after treatment by using fur
      plucks (FP), deep skin scrapes (DSS), and PCR analysis of fur swabs. In addition,
      the presence of mites was confirmed through skin biopsies at 2 study endpoints (1
      wk [n = 5] and 12 wk [ n = 5] after treatment). Samples collected before
      treatment and from untreated mice were positive for D. musculi at all time points
      and by all test modalities. After treatment, all ivermectin-treated animals
      remained infested, whereas mice treated with MI were repeatedly negative by all
      test modalities. An additional shortened treatment trial revealed that 4 wk of MI
      (n = 7) was insufficient to eradicate mites. Neither treatment produced any
      evidence of adverse effects according to hematology, serum chemistry parameters,
      behavior, body weight, and histopathology. Of the 70 PCR assays performed in
      treated mice, 14 were positive when FP+DSS was negative. In 6 cases where PCR
      results were negative, 5 were positive by FP+DSS and a single sample was positive
      on skin biopsy. Although PCR analysis has a high detection rate for D. musculi,
      FP+DSS can further enhance the detection rate. In conclusion, topical MI
      administered for 8 consecutive weeks can safely eradicate D. musculi from an
      immunocompromised mouse strain.

PMID- 30185288
TI  - The Other Side of the Opioid Debate: Treating Older Adults With Chronic Pain.
AB  - Prescriptions for opioids and opioid-related overdoses have been on the rise-and
      in the news-in the United States for more than a decade. New guidelines and
      legislation related to opioid prescribing provide clinical challenges for many
      pharmacists and prescribers, particularly in the treatment of older adults with
      chronic pain. Careful patient selection, along with proper opioid dosing and
      monitoring, enables the pharmacist and prescriber to continue to treat the older
      adult with pain effectively.

PMID- 30185286
TI  - Effects of Extruded Compared with Pelleted Diets on Laboratory Mice Housed in
      Individually Ventilated Cages and the Cage Environment.
AB  - The physical form of the diet fed to laboratory animals should be evaluated to
      reduce experimental variations and confoundingfactors. This 14-d study evaluated
      the effects of diet form (pelleted or extruded) on intracage ammonia
      concentrations,feed disappearance, body weight, cage weight, and the degree of
      cage soilage and whether these effects were influenced bystrain or stock or sex.
      Mice (C57BL/6, ICR, and nude; age, 4 wk) were randomly assigned to 4 treatment
      groups representingpelleted and extruded diets from each of 2 vendors (pelleted
      diet groups, P1 and P2; extruded diet groups, E1 and E2).Intracage ammonia
      concentrations depended on strain or stock, diet, and day and were higher in
      cages housing nude micethat consumed P1. Diet type did not affect the weight of
      mice at the end of the study. Feed disappearance was dependent ondiet type and
      mouse strain or stock and was greatest in the cages of mice that consumed P1. In
      addition, the greatest feeddisappearance was seen with ICR mice, whereas the
      least was seen with C57BL/6 mice. Cages housing male nude mice hadgreater cage
      soilage than those housing female nude mice. The degree of cage soilage was
      influenced by diet type and dayalso. These results show that diet form and mouse
      strain or stock significantly affect intracage ammonia concentrations,
      feeddisappearance, cage weight, and the degree of cage soilage.

PMID- 30185289
TI  - Medication Regimen Complexity Index in the Elderly in an Outpatient Setting: A
      Literature Review.
AB  - Objective To review current literature reporting outcomes associated with
      utilization of the Medication Regimen Complexity Index (MRCI) with older adults
      in an outpatient setting. Data sources The National Library of Medicine via
      PubMed, International Pharmaceutical Abstracts, and the Cochrane Database were
      used to identify clinical trials evaluating outcomes associated with utilization
      of the MRCI. The medical subject heading terms "geriatrics" and "medication
      adherence" were used in combination with key terms "medication regimen complexity
      index" and "medication complexity." Study selection/data extraction Seventy-five
      articles met the search criteria and were reviewed. Studies were included if they
      had MRCI-related outcomes and were performed in patients 60 years of age and
      older in an outpatient setting. Eleven articles met the stated criteria. Data
      synthesis Higher MRCI scores may be associated with increased mortality rates,
      medication nonadherence, and unplanned hospitalizations; however, when compared
      with medication number, MRCI did not better predict increased medication
      nonadherence and unplanned hospitalizations. Conclusion The MRCI is a useful tool
      to determine medication complexity; however, current literature is limited by its
      observational design. Also, MRCI does not take into account potential factors
      such as high-risk medications and comorbid conditions, which may affect MRCI
      scores; therefore, additional trials are warranted before suggesting pharmacists
      implement this tool in their everyday practice.

PMID- 30185290
TI  - Proton Pump Inhibitor Use in Older Adults: Long-Term Risks and Steps for
      Deprescribing.
AB  - Proton pump inhibitors (PPIs) are commonly prescribed for treatment of acid
      related gastrointestinal disorders. PPI use is approved for a duration of 2 to 12
      weeks, depending on complication and severity. Many users lack an appropriate
      indication for continued therapy past the recommended duration. Long-term PPI use
      is associated with several adverse drug events, including acute interstitial
      nephritis, fractures, and Clostridium difficile-associated diarrhea (CDAD).
      Cautious prescribing and regular monitoring is essential, especially for older
      adults, as they may be at higher risk for these adverse effects. Deprescribing,
      defined as lowering dosage, switching to as-needed use, or complete
      discontinuation, should be considered for many PPI users. Patient education is
      critical. Alternative therapy considerations include histamine-2-receptor
      antagonists, as they are found to be associated with reduced CDAD and fracture
      events. Additional strategies include tapering off PPIs and modifying lifestyle
      to reduce the potential rebound hypersecretion that may occur as a result of
      discontinuation. The most significant lifestyle modification is weight loss.
      Additional lifestyle interventions include upright head of bed elevation,
      avoiding meals close to bedtime, and avoiding high-fat meals within two to three
      hours of reclining.

PMID- 30185291
TI  - A Predictive Model to Identify Skilled Nursing Facility Residents for Pharmacist
      Intervention.
AB  - Objective Develop a predictive model to identify patients in a skilled nursing
      facility (SNF) who require a clinical pharmacist intervention. Design
      Retrospective, cross-sectional. Setting Nine freestanding SNFs within an
      integrated health care delivery system. Patients Patients who received a clinical
      pharmacist medication review between January 1, 2016, and April 30, 2017.
      Identified patients (n = 2,594) were randomly assigned to derivation and
      validation cohorts. Interventions Multivariable logistic regression modeling was
      performed to identify factors predictive of patients who required an intervention
      (i.e., medication dose adjustment, initiation, or discontinuation). Patient
      specific factors (e.g., demographics, medication dispensings, diagnoses) were
      collected from administrative databases. A parsimonious model based on clinical
      judgment and statistical assessment was developed in the derivation cohort and
      assessed for fit in the validation cohort. Main Outcome Measures Model to predict
      patients requiring clinical pharmacist intervention. Secondary outcome was a
      comparison of factors between patients who did and did not receive a clinical
      pharmacist intervention. Results Ninety-five factors were assessed. The
      derivation (n = 1,299) model comprised 22 factors (area under the curve [AUC] =
      0.79, 95% confidence interval [CI] 0.74-0.84). A clopidogrel dispensing (odds
      ratio [OR] = 2.42, 95% CI 1.19-4.91), fall (OR = 2.47, 95% CI 1.59-3.83), or
      diagnosis for vertebral fracture (OR = 2.33, 95% CI 1.34-4.05) in the 180 days
      prior to clinical pharmacist medication review were predictive of requiring an
      intervention. The model fit the validation cohort (n = 1,295) well, AUC = 0.79
      (95% CI 0.74-0.84). Conclusion Administrative data predicted patients in a SNF
      who required clinical pharmacist intervention. Application of this model in real
      time could result in clinical pharmacist time-savings and improved pharmacy
      services through more directed patient care.

PMID- 30185292
TI  - Anticoagulant Use in High Stroke-Risk Patients With Nonvalvular Atrial
      Fibrillation.
AB  - : Background Oral anticoagulants (OACs) are recommended for nonvalvular atrial
      fibrillation (NVAF) patients with moderate-to high-stroke risk. Objective To
      examine nationally reflective OAC usage in incident NVAF patients longitudinally.
      Design Three-year retrospective cohort analysis. Setting Medicare Part D
      recipients in the contiguous United States. PARTICIPANTS: 52,465 Medicare
      beneficiaries with incident NVAF in 2010 with two or more atrial fibrillation
      diagnoses seven or more days apart. Main outcome measure Stroke risk via
      congestive heart failure, hypertension, age greater than or equal to 75,
      diabetes, stroke, vascular disease, age 65-74, sex category (CHA2DS2-VASc) score.
      Primary outcome was proportion of patients receiving one or more OACs post-NVAF
      diagnoses. Results Of 48,980 high-risk patients, 32.7% received one or more OAC
      within 60 days of diagnosis. By close of 2011, 48% had one or more OAC. OAC use
      increased to 52.9% by close of 2012. Conclusions Fewer than 33% of high-risk NVAF
      patients received OACs within 60 days of diagnosis in 2010. Despite increased use
      over time, oral anticoagulation was below 53% at study end. Use of OACs declined
      with CHA2DS2-VASc greater than 6. Expanded efforts are warranted to augment OAC
      use in high stroke-risk patients.

PMID- 30185293
TI  - How Long-Term Care Is Changing.

PMID- 30185294
TI  - Decision Tool for Predicting Outcomes in Geriatric Acute Mesenteric Ischemia.
AB  - Acute mesenteric ischemia is a morbid disease process that is most common in
      elderly patients who often have multiple medical comorbidities. Intervention can
      progress to costly and futile care. The goal of this study was to develop a tool
      for practitioners to assess the risk of mortality. Patients treated at our
      institution over the past decade diagnosed with acute mesenteric ischemia were
      identified. Patients aged less than 65 years were excluded. Data were collected
      by retrospective chart review. Univariate analysis was used to identify
      significant risk factors for death. Decision tree analysis yielded a prognostic
      tool to assess death risk. Univariate analysis demonstrated that lactate (P <=
      0.001) and pressor requirement (P <= 0.001) were predictive of death. Decision
      tree analysis showed that 79 per cent of patients with day of surgery (DOS)
      lactate >=5.4 died postoperatively. Seventy per cent of patients with DOS lactate
      <5.4 progressed to death if they required pressors and had a creatinine >1.18.
      Only 6.1 per cent patients with a DOS lactate <5.4, creatinine <1.54, and no
      pressor requirement progressed to death. Several variables can be used to set
      expectations for families and help guide decision-making. Our tool was predictive
      of outcomes in 82 per cent of our study population.

PMID- 30185295
TI  - Use of Telemedicine in Surgical Education: A Seven-Year Experience.
AB  - Uniformity in surgical education is challenging because surgical experience is
      based on rotation assignments. With work hour restrictions, the likelihood of
      residents being exposed to rare or unusual cases is diminished. Telemedicine may
      create a new learning paradigm for surgical education and supplement exposure for
      rare or unusual cases. A retrospective review (2010-2016) of teleconferences
      involving trauma centers worldwide was conducted. Participating hospitals
      included centers from underdeveloped countries to first world nations. Trauma
      cases were discussed among surgeons with different levels of experience and
      resource availability. Data collected included types of cases, anatomic injury
      patterns, hospital location, and the number of telemedicine centers and viewers
      participating. Seventy-three hospitals in 64 cities, spanning 27 countries,
      participated in 276 telemedicine grand round conferences. Cases discussed
      included penetrating trauma (47%), blunt trauma (42%), and blast injury (4%). The
      anatomic regions included were the thorax (28%), abdomen (26%), thoracoabdominal
      region (13%), neck (7%), and pelvis (6%). The most common injury discussed was
      vascular in nature (18%), followed by the lung, liver, diaphragm, and heart. The
      most common vascular lesion was in the aorta (18%), followed by the iliac vessels
      (8%) and the vena cava (7%). Telemedicine is a valuable tool, allowing the
      dissemination of diverse experiences. Most cases presented evaluated rare
      injuries or complex surgical approaches, which are not commonly seen on trauma
      sites. Learning different approaches in the management of complex trauma will
      make surgeons more prepared to deal with challenging cases.

PMID- 30185296
TI  - A 12-Year Single-Institution Experience with Accelerated Partial Breast
      Irradiation.
AB  - Accelerated partial breast irradiation (APBI) using the implanted brachytherapy
      device MammoSite(r) was approved for routine use by the Food and Drug
      Administration in 2002. The American Society of Breast Surgeons MammoSite(r)
      Breast Brachytherapy Registry served as a guideline for our institution to begin
      offering this treatment in 2005. This report reviews our available data to
      provide an analysis of patient outcomes over 12 years of use at a single
      institution. A retrospective review was conducted of records of 150 patients who
      underwent APBI or attempted APBI after breast-sparing surgeries between 2006 and
      2017. These charts were analyzed for documentation of patient age, cancer stage,
      incidence of recurrence, and posttreatment complications. Of the patients
      evaluated, 99 per cent (149/150) completed treatment. The median time since
      treatment completion is now 8.9 years. One hundred eleven patients (74% ) are now
      greater than five years posttreatment. Ipsilateral breast recurrence was found in
      2.7 per cent of patients (4/149), and 1.3 per cent of patients (2/149) developed
      new primary breast tumors. Acute complications, mostly skin erythema (21%), were
      uncommon and self-limited. Subacute effects were generally fibrosis (13%) and
      mild local pain (9.4%). APBI for breast cancer after breast-conserving surgery
      continues to be used at our institution for select patients with good outcomes.
      Local control and toxicity are similar to that reported in the literature. Five
      year local recurrence rates compare favorably with national trials. Occasional
      complications included fibrosis, persistent pain, and skin irritation.

PMID- 30185297
TI  - Negative Sestamibi Scans Predict Lower Likelihood of Surgical Referral in
      Patients with Primary Hyperparathyroidism.
AB  - 99mTechnetium sestamibi scans (MIBI) can provide negative or inaccurate results
      in patients with biochemical primary hyperparathyroidism. Reliance on MIBI as a
      diagnostic modality rather than as a localization tool leads to misdiagnosis and
      inappropriate care. The aim of this study was to determine the impact of negative
      MIBI scans on referral patterns and surgical intervention. Adults with MIBI scans
      at our institution from January 1, 2011, to May 31, 2017, were retrospectively
      reviewed. Data collected include demographics, study date and results, ordering
      physician specialty, pre/postoperative laboratories, and operative and final
      pathology. Statistical analysis was performed with SPSS v24 (IBM Corp., Armonk,
      NY). Three hundred fifty-seven patients had a MIBI scan; 10 were excluded for
      incomplete data or incorrect diagnosis. One hundred eighty-six were interpreted
      as positive (53.6%) and 161 were interpreted as negative (46.4%). Of the 186
      positive MIBI scans, 135 (72.6%) were seen by an endocrine surgeon (ES). Of these
      135 patients, 111 (82.2%) underwent parathyroidectomy. Of the 161 negative MIBI
      scans, 69 (42.9%) were seen by an ES. Of these, 53 (76.8%) underwent
      parathyroidectomy. In all, 90/92 (97.8%) with a negative MIBI scan who were not
      seen by an ES did not have surgery. Nonendocrine surgeon physicians are more
      likely to use MIBI scans as diagnostic tools to assist with clinical decision
      making. Patients with a negative MIBI scan not seen by an ES were significantly
      less likely to undergo parathyroidectomy. Patients with primary
      hyperparathyroidism should be referred to an experienced parathyroid surgeon for
      evaluation, regardless of the MIBI result.

PMID- 30185298
TI  - Imaging-Associated Radiation Trends in a Puerto Rican Pediatric Surgical
      Population: Is Over-Radiation an Issue in Our Emergency Departments?
AB  - The increased use of CT scans has raised concerns regarding the risks of early
      radiation exposure in the Puerto Rico pediatric population. Available literature
      sustains that repeated exposure to imaging-related radiation in the pediatric
      population is associated with a 3-fold increase in the risk of developing
      pediatric hematogenous and central nervous system malignancies. It is for this
      reason that an international effort known as the Image Gently Campaign was
      created, mostly based on the "As Low As Reasonably Achievable" (ALARA) principle
      described by the Center for Disease Control. With this in mind, our aim was to
      identify whether there are any discrepancies in imaging tendencies outside our
      pediatric academic center in Puerto Rico and to determine whether our patients
      are at increased risk of over-radiation. There were 181 patients; five were
      excluded because of incomplete data. Our results show that children with
      appendicitis who are evaluated at nontertiary centers are more likely to have a
      CT scan performed (93%, OR: 4.054; 95% confidence interval: 2.6-6.4), as opposed
      to a nonradiating imaging study. In the Pediatric University Hospital, a CT scan
      was performed as the initial study in 23 per cent of the patients (OR: 0.09; 95%
      confidence interval: 0.05-0.18), favoring ultrasound as the diagnostic modality
      of choice. Our concern is that if this trend does not change, our pediatric
      population might have an increased risk of developing associated malignancies. We
      believe a local effort toward educational strategies should be implemented to
      prevent radiation overexposure in our pediatric patients.

PMID- 30185299
TI  - Postdischarge Mortality after Geriatric Low-Level Falls: A Five-Year Analysis.
AB  - Geriatric trauma patients with low-level falls often have multiple comorbidities
      and limited physiologic reserve. Our aim was to investigate postdischarge
      mortality in this population. We hypothesized that five-year mortality would be
      higher relative to other blunt mechanisms. The registry of our Level 1 trauma
      center was queried for patients evaluated between July 2008 and December 2012.
      Adult patients identified were matched with mortality data from 2008 to 2013 from
      the National Death Index. Low-level falls were identified by E Codes; other types
      of blunt trauma were based on registry classification. Patients with multiple
      admissions were excluded. Univariate analysis was performed using Fisher's exact
      and Wilcoxon tests. Kaplan-Meier curves were plotted to compare postdischarge
      mortality. Seven thousand nine hundred sixteen patients were evaluated, 35.1 per
      cent were females. Patients aged less than 65 years and penetrating trauma were
      excluded, yielding 1997 patients-63.7 per cent with low-level falls versus 36.3
      per cent with other blunt traumas. Geriatric patients sustaining low-level falls
      were older, more likely female, had a higher inpatient mortality, and were less
      likely to return home at discharge. Injury severity score, hospital length of
      stay, and intensive care unit length of stay were similar. Survival analysis
      demonstrated increased postdischarge mortality in the low-level fall group with
      25 per cent mortality at 120 days. Geriatric patients with other blunt trauma had
      a significantly lower postdischarge mortality. Geriatric patients injured in low
      level falls have a higher inhospital mortality, are more likely to be
      functionally dependent on discharge, and have a high postdischarge mortality.
      Opportunities likely exist for injury prevention, consideration of palliative
      care, and postdischarge rehabilitation.

PMID- 30185300
TI  - Being Narrow Minded Is Not Always Bad: Focusing on Emergent Interventions in
      Undertriage Initiatives Improves Mortality Prediction.
AB  - The American College of Surgeons Committee on Trauma defines undertriage (UT) as
      any major trauma patient (injury severity score >= 16) not undergoing treatment
      at the highest level of trauma team activation. This methodology does not account
      for many important factors that may impact outcome. We performed a retrospective
      review of the Pennsylvania State Trauma Registry to determine the impact of
      treatment interventions on mortality. Patients were stratified by triage category
      as follows: UT, appropriate triage, and overtriage. Multiple prehospital (PH) and
      ED interventions were assessed. Increased mortality was observed in all triage
      groups in patients requiring intervention. A logistic regression analysis was
      performed to assess the independent effect of individual interventions on
      mortality for patients triaged to partial activation or consult. PH CPR (OR 66.13
      [47.07-92.93]), ED CPR (OR 16.87 [8.82-32.27]), PH or ED intubation (OR 16.68
      [13.90-20.03]), PH or ED packed red blood cell transfusion (OR 1.89 [1.54-2.33]),
      emergent operative intervention (OR 3.58 [3.07-4.19]), ED central venous access
      (OR 5.04 [2.31-10.97]) were all associated with worsening mortality. The American
      College of Surgeons Committee on Trauma methodology overestimates mortality risk
      when emergent interventions are not required and underestimates risk where such
      interventions are necessary. Future methodologies for assessing UT should include
      these interventions.

PMID- 30185301
TI  - Moderate Sedation or Monitored Anesthesia Care for Colonoscopies: Is There a
      Difference?
AB  - To determine whether monitored anesthesia care (MAC) results in shorter
      colonoscopy time. A retrospective chart review from electronic medical records at
      Sentara Norfolk General Hospital was performed of all patients seen by the
      Eastern Virginia Medical School Department of Surgery who underwent a screening
      or diagnostic colonoscopy from December 2015 to July 2017. The primary end point
      is procedure time, with secondary end point of sedation time. There is a
      statistically significant difference in time to cecum between moderate sedation
      (MOD) and MAC (P = 0.002). Operator perceived difficulty is statistically
      associated with increased time to cecum (P < 0.0001). Time to cecum between MOD
      and MAC over the levels of difficulty was not significant (P = 0.403). A
      subanalysis looking at time to cecum between MOD and MAC for each level of
      difficulty showed a significant effect when difficulty was described as no
      difficulty. There is a statistically significant difference in time to scope
      insertion between MOD and MAC (P < 0.0001). Our data show that, taken as a
      conglomerate, the procedure and sedation time is shorter in MAC than in MOD. The
      use of MAC is associated with decrease time to scope insertion and overall time
      to cecum.

PMID- 30185303
TI  - Discrepancy in Postoperative Outcomes between Auditing Databases: A NSQIP
      Comparison.
AB  - In 2014, ACS-NSQIP(r) targeted pancreatectomies to improve outcome reporting and
      risk calculation related to pancreatectomy. At the same time, our department
      began prospectively collecting data for pancreatectomy in the Enhanced Recovery
      After Surgery(r) Interactive Audit System (EIAS). The purpose of this study is to
      compare reported outcomes between two major auditing databases for the same
      patients undergoing pancreatectomy. The same 171 patients were identified in both
      databases. Clinical outcomes were then obtained from each database and compared
      to determine whether reported complication rates were statistically different
      between auditing databases. A combination of Wilcoxon rank sum and Pearson's chi
      squared tests were used to calculate statistical significance. No significant
      difference was appreciated in captured demographics between EIAS and NSQIP.
      Significant differences in reported rates for renal dysfunction, postoperative
      pancreatic fistula, return to the operative room, and urinary tract infection
      were noted between EIAS and NSQIP. Although significant differences in reported
      complication rates were demonstrated between EIAS and NSQIP for pancreatectomy,
      much of the discrepancy is attributable to subtle differences in definitions for
      postoperative occurrences between the two auditing databases. It is vital for
      surgeons to understand the exact definition that determines the complication rate
      for a given database.

PMID- 30185302
TI  - Defining Outcomes after Colon Resection in Blunt Trauma: Is Diversion or Primary
      Anastomosis More Favorable?
AB  - Previous literature demonstrates the safety of primary repair in penetrating
      colon injury requiring resection, without the creation of a diverting ostomy. It
      is unknown whether a similar approach can be applied to patients with blunt colon
      injury. The aim of this study was to measure outcomes in patients who underwent
      colon resection with and without ostomy creation after blunt trauma injury to
      help direct future management. Using the National Trauma Data Bank for years 2008
      to 2012, we identified patients with blunt trauma mechanisms who underwent
      colectomy. Patients were stratified into two groups: primary anastomosis and
      diversion with ostomy. Primary outcome was inpatient mortality. Secondary
      outcomes included length of stay and perioperative complications. All risk
      adjusted analyses were performed using logistic regression with consideration of
      interactions. Five hundred eighty-one observations met our inclusion criteria.
      Baseline characteristics between the two groups were similar with the exception
      of age (37.3 vs 42.2 years, P < 0.001) and admission Glasgow coma score (13.2 vs
      12.1, P = 0.002). Risk-adjusted mortality for the two groups was not
      statistically significant (2.3% vs 3.0%, P = 0.63); however, patients with
      primary anastomosis had a shorter length of stay (18.2 vs 28.1, P < 0.001), fewer
      days in the intensive care unit (10.9 vs 16.2, P < 0.001), and fewer ventilator
      days (10.5 vs 14.6, P = 0.01). In patients requiring colon resection after blunt
      trauma, mortality is not different for those who receive a primary anastomosis
      versus ostomy. Patients without diversion had shorter hospital stays, intensive
      care unit days, and ventilator days. These data support that primary anastomosis
      is safe in this patient population.

PMID- 30185304
TI  - Is the Face an Air Bag for the Brain and Torso?-The Potential Protective Effects
      of Severe Midface Fractures.
AB  - We investigated the patterns of injury associated with major midface trauma. Our
      hypothesis is that midface injuries are associated with a decrease in certain
      traumatic brain injuries as well as major torso injuries. The registry of our
      Level I trauma center was queried for all adult patients treated over 25 years
      from 1989 to 2013. Patients with midface fractures were identified based on the
      ICD-9 code. Associated injuries were defined based both on individual ICD-9 codes
      as well as the Barell Injury Matrix. Injury etiology was defined based on e
      codes. Univariate analysis was performed using chi-squared test, Fisher's exact
      test, and Wilcoxon test. A total of 29,152 patients were identified. Excluding
      pediatric patients, those with exclusively penetrating trauma, and patients with
      incomplete data, 20,971 patients were included for subsequent analysis. Midface
      fractures were identified in 752 patients. Patients with Le Fort fractures were
      more likely to be male, have a higher Injury Severity Score, a lower arrival
      Glasgow Coma Scale, and more likely to require intensive care unit admission and
      mechanical ventilation, with a longer hospital length of stay. Patients with
      midface fractures had significantly fewer subdural hematomas, subarachnoid
      hemorrhages, spine fractures, and were less likely to have associated abdominal
      and pelvic injuries. Patients with midface fractures were more likely to require
      facial reconstruction procedures and craniotomy. Patients presenting with midface
      fractures after blunt trauma have a distinctly different pattern of injuries. One
      potential mechanism for this is a deceleration effect, where midface impact and
      resulting fractures dissipate some of the energy.

PMID- 30185305
TI  - Optimization of Resource Allocation after Implementation of Mild Traumatic Brain
      Injury Treatment Protocol.
AB  - The purpose of this study was to assess resource utilization after implementation
      of a mild traumatic brain injury (TBI) treatment protocol. A retrospective review
      was conducted of patients with isolated mild TBI before and after implementation
      of a mild TBI treatment protocol in May 2015. Patients admitted from June 2014 to
      February 2017, aged 18 to 89 years, presenting with a Glasgow coma score of 13 to
      15, with an isolated small intracerebral hemorrhage on CT without midline shift,
      and not coagulopathic were evaluated. According to the protocol, patients were
      admitted to a non-intensive care unit (ICU) ward, without routine neurosurgical
      consultation or repeat head CT unless clinically indicated. Hospital length of
      stay (LOS), ICU LOS, rate of neurosurgical consultation, rate of repeat head CT
      within 24 hours of admission, and associated costs were evaluated. Forty-six
      patients were identified in the preprotocol group and 97 in the protocol group.
      The protocol group had a shorter hospital LOS (1.46 vs 2.04 days, P = 0.0034),
      shorter ICU LOS (0.02 vs 0.37 days, P < 0.0001), lower rates of repeat head CT
      (2.06% vs 39.13%, P < 0.0001), and neurosurgical consultations (1.03% vs 28.26%,
      P < 0.0001). Decreased charges derived from fewer repeat head CT and
      neurosurgical consultations were observed from $43.98 to $844.04 per patient.
      There were no inpatient mortalities and no progressions of injury requiring
      unplanned admission to the ICU or operative intervention. Efficient delivery of
      care is paramount in modern medicine and this study demonstrates that the mild
      TBI treatment protocol significantly decreased resource utilization without
      jeopardizing patient safety.

PMID- 30185306
TI  - The Surgical Experience Aboard USNS COMFORT (T-AH-20) during Operation Continuing
      Promise 2015.
AB  - In 2015, the United States Navy hospital ship (USNS) COMFORT, deployed to 11
      Caribbean and Latin American countries over a six-month period to provide
      humanitarian civic assistance. Personnel from the United States Navy and multiple
      nongovernmental organizations collaborated to offer surgical and medical care.
      Data from past deployments aid in planning for future missions by prioritizing
      finite resources and maximizing care. The data analyzed included all patients
      evaluated and treated by the Directorate of Surgical Services of the USNS COMFORT
      between April and September 2015. Comparative and descriptive statistics were
      performed to analyze patient demographics, surgical subspecialty performing the
      procedures, types of general and pediatric surgical procedures performed,
      operative times, and complication rates. Of the 1256 surgical cases performed
      aboard USNS COMFORT during CP15, 24.8 per cent were general surgery cases,
      followed by 16 per cent ophthalmology, 10.6 per cent pediatric surgery, 10 per
      cent plastic surgery, and eight additional specialties with <10 per cent of the
      cases each. Total operative time was 1253 hours with a total room time of 1896.5
      hours. The identified complication rate was 1.99 per cent across all specialties.
      The USNS COMFORT platform offers the unique capability to provide humanitarian
      surgical assistance. Reporting these data demonstrate that there is a need for
      humanitarian assistance and this can be provided safely through the Continuing
      Promise mission. Future deployments may target resources toward the surgical
      services with higher volumes, which were general surgery, ophthalmology,
      pediatric surgery, and plastic surgery.

PMID- 30185307
TI  - South Carolina Surgical Quality Collaborative Colon Surgery Outcomes Vary by Age
      and Race.
AB  - Identifying disparities in surgical outcomes among patient populations may help
      hospitals target patients at highest risk for complications. The South Carolina
      Surgical Quality Collaborative (SCSQC) is a regional collaborative made up of
      eight facilities whose goal is to improve the quality and value of general
      surgical care in South Carolina. Using SCSQC data, we reviewed colon surgery
      outcomes to determine whether disparities exist between specific patient
      populations. SCSQC colon surgery data were reviewed from August 2015 to August
      2017. SSI, length of stay, return to the ED, and reoperation rates were used as
      outcome measures. They were evaluated in patient populations stratified by
      gender, race (white, black, and other), and age (<50, 50-70, and >70 years). A
      total of 2611 patients were included in this study. Statistically significant
      differences in outcomes were identified between white and black patients in
      length of stay (6.0 vs 7.5 days, P < 0.0001) and return to the ED (8.1% vs 14.7%,
      P < 0.0001), but not in SSI (6.4% vs 6.8%, P = 0.8839) or reoperation rates (6.4%
      vs 8.4%, P = 0.1886). Length of stay increased with increasing age (4.1 vs 7.1 vs
      8.8, P < 0.0001). SSI varied by age (4.0% vs 8.2% vs 6.4%, P = 0.0005), as did
      return to the ED (11.2% vs 9.7% vs 769%, P = 0.0987) and reoperation rates (4.5%
      vs 8.1% vs 8.2%, P = 0.0034). SCSQC data indicate that race and age may place
      patients at risk for negative outcomes after colorectal surgery.

PMID- 30185308
TI  - Long-Term Effects of Decompressive Craniectomy on Functional Outcomes after
      Traumatic Brain Injury: A Multicenter Study.
AB  - Decompressive craniectomy (DC) is a surgical modality sometimes used in the
      management of elevated intracranial pressure. Questions remain as to its long
      term benefits in traumatic brain injury patients. The extended Glasgow Outcome
      Scale (eGOS) is a scoring system based on a structured interview that allows for
      consistent and reproducible measurement of long-term functional outcomes. The
      purpose of this study was to determine the eGOS score of postcraniectomy patients
      after discharge and stratify survivors based on outcome. A multicenter review of
      patients who underwent DC was performed. Survivors underwent a phone survey at
      which time the eGOS was calculated. Patients with an eGOS >= 5 were considered to
      have a good functional outcome. Fifty-four patients underwent DC. Age (OR 1.038;
      confidence interval 1.003-1.074) and Glasgow Coma Scale (OR 0677; confidence
      interval 0.527-0.870) were predictors of mortality. Patients who were available
      for follow-up (n = 13) had poor functional outcomes at discharge (eGOS = 3);
      however, this improved at the time of follow-up survey (eGOS = 5; P = 0.005). DC
      is a controversial operation with high mortality and uncertain benefit. Among our
      cohort, the eGOS score was significantly higher at follow-up survey than it was
      at discharge. Although the mortality was high, if patients survived to discharge,
      most had a good functional outcome at follow-up survey.

PMID- 30185309
TI  - Recurrence Patterns after Primary Excision of Invasive Melanoma with Melanoma in
      situ at the Margin.
AB  - The significance and management of melanoma in situ (MIS) at the margin of
      excision of invasive melanoma is debated. Patients undergoing excision of
      invasive melanoma from 2000 to 2016 with MIS at the margin were identified. A
      cohort without MIS was matched for age, gender, location, and Breslow depth.
      Thirty-two patients with 33 cases of MIS at the margin were identified. Melanoma
      was located on the head/neck (66.7%), extremities (24.2%), and trunk (9.1%).
      Median Breslow depth was 1.0 mm (range 0.25-10.80). Margin treatment included re
      excision (45.5%), re-excision plus imiquimod (3.0%), imiquimod alone (9.1%), and
      observation alone (42.4%). At a median follow-up of 91 months (range 28-126),
      five patients (15.2%) with a median Breslow depth of 4.75 mm (range 1.10-6.70)
      developed local recurrence (LR). Three underwent re-excision of the positive
      margin and two were observed. Intervention for positive margins did not decrease
      LR compared with observation (P = 0.905, OR = 1.125, 95% confidence interval [CI]
      0.162-7.824). All five patients with LR were alive at the last follow-up. There
      were two recurrences in the matched cohort (6.1%); both were alive at the last
      follow-up. Risk of LR is higher with MIS at the margin, but this does not seem to
      impact survival. Larger studies may elucidate predictive factors and
      interventions that decrease risk for LR.

PMID- 30185310
TI  - Accuracy of MRI in Diagnosing Appendicitis during Pregnancy.
AB  - Appendectomy for presumed appendicitis is the most common surgical emergency
      during pregnancy. Delayed diagnosis and treatment of appendicitis carries risk
      for the fetus and mother. We sought to evaluate the accuracy of MRI in pregnant
      patients with suspected appendicitis. All pregnant patients with suspected
      appendicitis between January 2014 and April 2016 were included. MRI reports were
      categorized into positive, negative, and inconclusive groups. Diagnosis of
      appendicitis was based on pathology report. Fifty-two patients were included in
      the study. The MRI was positive in two, negative in 29, and inconclusive in 21
      patients. Twelve patients had surgery, 11 of which had positive appendicitis on
      pathology. Both positive MRI patients had appendicitis. In the negative MRI
      group, 3 of 29 (10%) had appendicitis. In the inconclusive MRI group, 6 of 21
      (29%) had appendicitis. A positive MRI result was very specific with a 100 per
      cent positive predictive value; however, the sensitivity was as low as 18 per
      cent (diagnosed only 2 of 11 cases). Although a positive MRI finding was reliable
      in making a decision to operate, a negative or inconclusive MRI was not. In
      patients with a high clinical suspicion of appendicitis, surgery should still be
      considered even without definitive positive MRI findings.

PMID- 30185311
TI  - Cost Effectiveness of Different Methods of Appendiceal Stump Closure during
      Laparoscopic Appendectomy.
AB  - There is no standard method for closure of an appendiceal stump during
      laparoscopic appendectomy. This study compares stump closure using a stapler with
      closure using an Endoloop ligature. The charts of all patients who underwent
      laparoscopic appendectomy at a single tertiary care center over a two-year period
      were reviewed for demographics, comobidities, operative details and costs, and
      outcomes. There were 325 patients who underwent a laparoscopic appendectomy. The
      majority, 250 (77%), underwent stump closure with a stapler. They were equivalent
      in demographics and postoperative complication rates. Cases using an Endoloop
      were slightly faster in terms of procedure time and room time, and less expensive
      in terms of operative supply cost. The price difference is not explained by time
      saved in the operating room and more likely by the equipment price.

PMID- 30185312
TI  - Propofol Infusion Syndrome: Efficacy of a Prospective Screening Protocol.
AB  - Propofol infusion syndrome (PIS) is a potentially lethal complication of propofol
      marked by rhabdomyolysis, metabolic acidosis, and cardiac arrhythmias or
      collapse. The objective of this study was to determine the effectiveness of a
      prospective screening protocol to prevent PIS. All trauma patients admitted who
      received propofol as a continuous infusion were prospectively screened from
      November 1, 2013 to December 31, 2015. Variables studied included demographics,
      injury severity, laboratory values, infusion rates, and mortality. Serum creatine
      phosphokinase (CPK) and lactate were drawn daily. Propofol was stopped for a
      positive screen defined as an increase in CPK to greater than 5000 IU/L or
      lactate greater than 4 mmol/L. Positive and negative cohorts were compared. Two
      hundred and twenty-five patients met the inclusion criteria and 12 patients
      (5.3%) had propofol stopped because of elevated CPK. No differences were
      identified in demographics, transfusions, injury severity, hospital length of
      stay, or propofol dose. The positive screened group had longer intensive care
      unit length of stay (20 vs 13 days; P = 0.002) and increased vent days (14.5 vs
      10 days; P = 0.008). Max serum osmolality (334 vs 305 mosm/kg; P = 0.049) and max
      serum CPK (6782 vs 1058 IU/L; P < 0.0001) were higher in the positive cohort. No
      cases of PIS occurred, and mortality (16.7 vs 15.5%; P = 0.999) was not different
      between the cohorts. The screening protocol was effective in eliminating PIS.
      Serial CPK evaluations provided an effective screening tool and serum lactate can
      be dropped from screening.

PMID- 30185313
TI  - Dogma without Data: A Clinical Decision-Making Tool for Postoperative Blood
      Cultures.
AB  - Bacteremia is a worrisome postoperative complication and blood cultures (BCx) are
      often nondiagnostic. We previously reported a 4 per cent overall yield of
      positive cultures in postoperative patients. To reduce unnecessary testing, we
      present a predictive model to identify patients in whom growth of pathogens is
      unlikely and provide a clinical decision-making guide. Retrospective analysis of
      nonpregnant patients >=18 years who had BCx within 10 days postoperatively was
      performed. Generalized linear mixed models identified clinical predictors of high
      and low-yield cultures. A clinical algorithm was created using significant
      predictors, and positive predictive value, negative predictive value,
      sensitivity, and specificity calculated. Among 1759 BCx, hypotension, maximum
      temperature >=101.5  degrees F within 24 hours of culture, and culture collected
      after postoperative day (POD) two were statistically significant predictors of
      positive cultures. Forty nine per cent of BCx were sent <= POD 2, and <1 per cent
      of these were positive. When all three criteria were met, the probability of a
      positive culture increased to 17 per cent. When absent, the probability of a
      negative culture was 99 per cent. When applied to the initial data set, the model
      resulted in 85 per cent reduction of cultures with 9 per cent yield of positive
      cultures. Drawing BCx based on a single predictor is inadequate. Reducing the
      number of cultures reflexively ordered within the first two POD could
      significantly reduce the number of unnecessary BCx. Several clinical features
      identified patients most likely to have positive BCx within the first 10 POD and
      could reduce unnecessary BCx. This model should be validated in an independent,
      prospective cohort.

PMID- 30185314
TI  - The Natural History of Gastrointestinal Bleeding in Patients without an Obvious
      Source.
AB  - With the advent of proton pump inhibitors and H. Pylori treatment, the old dogma
      "the most common cause of lower GI bleeding is upper GI bleeding" may no longer
      be valid. We sought to determine the most common causes of GI bleeding in
      patients without an obvious source and their clinical outcomes. We queried our
      hospital database for GI hemorrhage during 2015, excluding patients with obvious
      sources such as hematemesis or anal pathology. We collected data from patients
      with GI bleeding defined as bright red blood per rectum, melena, or a positive
      fecal occult blood test. The primary endpoints were etiology of GI bleed, amount
      of transfusions required, and types of interventions performed. Ninety-three
      patients were admitted with GI bleeding as defined previously: mean age was 74
      years and mean hemoglobin was 8.2. Seventy-four per cent received blood
      transfusions with an average of 2 units transfused per patient; 22 per cent
      received 3 or more units of blood. The etiology of bleeding was 17 per cent upper
      GI source, 15 per cent lower GI source, and in 68 per cent, the source remained
      unknown. Bleeding stopped spontaneously in 86 per cent of patients and 9 per cent
      died. Endoscopy was performed in 71 per cent, but only 6 per cent underwent
      therapeutic endoscopic intervention. No patient had surgical or interventional
      radiologic procedures related to their GI bleed. Gastrointestinal bleeding,
      without an obvious source on presentation, rarely requires operative intervention
      or interventional radiologic procedure. Blood transfusions were not predictive of
      the need for therapeutic endoscopic intervention which was required in only 6 per
      cent of patients.

PMID- 30185316
TI  - Tube Thoracostomy Management in the Combat Wounded.
AB  - The intent of this study was to characterize the management and subsequent
      complications of combat injury tube thoracostomies and to determine risk factors
      for the development of pneumonia (PNA) and retained hemothorax (RH). One hundred
      fifteen patients with 173 tube thoracostomies met the inclusion criteria and were
      analyzed. The mean injury severity score was 30.8 + 11.6, 23.5 per cent had
      traumatic amputations, 49.7 per cent had a hemothorax, and 50.3 per cent had a
      pneumothorax as indications for tube thoracostomy (TT) placement. Within 24 hours
      of injury, 89.6 per cent were intubated, the majority (54%) were injured by
      improvised explosive devices, 35.6 per cent sustained rib fractures, and 12.2 per
      cent had a diaphragm injury. A mean of 1.5 + 0.7(range 1-4) tube thoracostomies
      were placed, 18.3 per cent of patients had bilateral tube thoracostomies, and the
      average TT duration was 6.7 + 3.9 days. The incidence of PNA was 27 per cent (n =
      31), RH was 9.6 per cent (n = 11), and empyema was 1.7 per cent (n = 2).
      Multivariable analysis identified the duration of ventilation [OR 1.2, 95%
      confidence interval (CI): 1.097-1.313, P < 0.001] as independently associated
      with the development of PNA. Bilateral TT placement (OR 3.848, 95% CI: 1.219
      12.143, P = 0.0216) and injury severity score (OR 1.050, 95% CI: 1.001-1.102, P =
      0.0443) were independently associated with PNA development when a patient was
      intubated for eight days or less. The number of tube thoracostomies placed (OR
      3.08, 95% CI: 1.03-9.18, P = 0.0439) was independently associated with the
      development of RH. Further research is warranted to identify modifiable risk
      factors to reduce the incidence of PNA and RH in patients with TT placed for
      traumatic injuries.

PMID- 30185315
TI  - Correlation between Depression, Posttraumatic Stress Disorder, and Inflammatory
      Factors in Patients with Severe Burn Injury.
AB  - We aim to investigate the relation between depression, posttraumatic stress
      disorder (PTSD), and inflammatory factors in patients with severe burn injury.
      Psychological assessment was carried out using PTSD checklist (PCL) involving a
      17-item self-report questionnaire (PCL-17) and the Hamilton Rating Scale for
      depression (HAMD-24). The serum IL-1beta, IL-6, IL-8, and tumor necrosis factor
      alpha (TNF-alpha) were determined using enzyme-linked immunosorbent assay.
      Correlation analysis was performed to analyze the correlation between the factors
      and scores of PTSD and depression. Compared with the PCL-17 score, HAMD-24 score,
      and inflammatory factors at month 3, a significant decrease was noticed in the
      PCL-17 score, HAMD-24 score, and inflammatory factors at months 6 and 9 (P <
      0.01). For the HAMD-24 score, significant improvements were noticed in the
      anxiety/somatization, cognitive disorder, blocking, sleep disorders, and
      depression at months 3, 6, and 9. The levels of IL-1beta, IL-8, and TNF-alpha
      were positively correlated with the PCL-17 score (P < 0.05). The levels of IL
      1beta, IL-6, IL-8, and TNF-alpha were positively correlated with the HAMD-24
      score (P < 0.05). Patients with severe burn injury showed obvious stress
      alternation displaying specific depression-related characteristics, and
      inflammation may involve in the pathogenesis of PTSD and depression in burn
      patients.

PMID- 30185317
TI  - Posterior Thoracic Stab Wounds: Evaluating the Value of Commonly Used Radiologic
      Modalities.
AB  - This study was performed to assess our institution's experience with stab
      injuries to the posterior mediastinal box. We examine the value of performing CT
      of the chest and esophagram in conjunction with a chest X-ray (CXR) over
      performing CXR(s) alone in evaluating this group of patients. We performed a
      retrospective study covering a 10-year period consisting of patients with stab
      wounds to the posterior mediastinal box. Age, gender, and injury severity score
      as demographic data points were collected. CXR, CT, and esophagram results;
      identified injuries; and subsequent interventions were analyzed. Of 78 patients
      who met the inclusion criteria, a total of 55 patients underwent esophagram, one
      had a false-positive result, and zero had their course altered by the study.
      Sixty-six patients underwent CT imaging, and there were nine missed findings on
      initial CXR. Five of these were clinically insignificant and the remaining four
      were managed with a chest tube alone. There were no tracheobronchial, esophageal,
      cardiac, or great vessel injuries. Hemodynamically stable, asymptomatic patients
      with stab wounds to the posterior mediastinal box do not require routine CT and
      esophagram in the absence of CXR and cardiac ultrasonographic abnormalities.

PMID- 30185318
TI  - The Price of Always Saying Yes: A Cost Analysis of Secondary Overtriage to an
      Urban Level I Trauma Center.
AB  - Level I trauma centers serve as a community resource, with most centers using an
      inclusive transfer policy that may result in overtriage. The financial burden
      this imparts on an urban trauma system has not been well examined. We sought to
      examine the incidence of secondary overtriage (SOT) at an urban Level I trauma
      center. This was a retrospective study from an urban Level I trauma center
      examining patients admitted as trauma transfers (TT) from 2010 to 2014. SOT was
      defined as patients not meeting the "Orange Book" transfer criteria and who had a
      length of stay of <48 hours. Average ED and transport charges were calculated for
      total transfer charges. A total of 2397 TT were treated. The number of TT
      increased over the study interval. The mean age of TT was 59.7 years (SD +/- 26.4
      years); patients were predominantly male (59.2%), white (83.2%), with at least
      one comorbidity (71.5%). Blunt trauma accounted for 96.8 per cent of admissions
      with a median Injury Severity Score of nine (IQR: 5-16). Predominant injuries
      were isolated closed head trauma (61.4%), skin/soft tissue injury (18.9%), and
      spinal injury (17.6%). SOT was 48.2 per cent and increased yearly (P < 0.001).
      The median trauma center charge for SOT was ($27,072; IQR: $20,089-34,087),
      whereas ED charges were ($40,440; IQR: $26,150-65,125), resulting in a total cost
      of $67,512/patient. A liberal TT policy results in a high SOT rate adding
      significant unnecessary costs to the health-care system. Efforts to establish
      transfer guidelines may allow for significant cost savings without compromising
      care.

PMID- 30185319
TI  - Correlating Geographic Location with Incidence of Motor Vehicle-Induced
      Pedestrian Injury.
AB  - To date, no studies have examined the relationship between geographic and
      socioeconomic factors and the frequency of pedestrians sustaining traumatic
      injuries from a motor vehicle. The objective of this study was to analyze the
      impact of location on the frequency of pedestrian injury by motor vehicle. The
      University of Louisville Trauma Registry was queried for patients who had been
      struck by a motor vehicle from 2010 to 2015. Demographic and injury information
      as well as outcome measures were evaluated to identify those impacting risk of
      pedestrian versus motor vehicle accidents. Number of incidents was correlated
      with lower median household income. There was also a moderate correlation between
      number of incidents and population density. Multivariable analysis demonstrated a
      significant association between increased median household income and distance
      from downtown Louisville and decreased risk of death after pedestrian versus
      motor vehicle accident. Incidence of pedestrian injury by motor vehicles is
      influenced by regional socioeconomic status. Efforts to decrease the frequency of
      these events should include further investigation into the mechanisms
      underpinning this relationship.

PMID- 30185320
TI  - Payer Source Associated with Disparities in Procedural, but Not Surgical, Care in
      a Trauma Population.
AB  - Trauma centers are legally bound by Emergency Medical Treatment and Active Labor
      Act to provide equal treatment to trauma patients, regardless of payer source.
      However, evidence has suggested that disparities in trauma care exist. This study
      investigated the relationships between payer source and procedures (total,
      diagnostic, and surgical) and the number of medical consults in an adult trauma
      population. This is a 10-year retrospective trauma registry study at a Level I
      trauma facility. Payer source of adult trauma patients was identified,
      demographics and variables associated with trauma outcomes were abstracted, and
      multivariate logistic regression tests were used to determine statistical
      differences in the number of procedures and medical consults. Of the 12,870
      records analyzed, 69.1 per cent of patients were commercially insured, 21.2 per
      cent were uninsured, and 9.6 per cent had Medicaid. After controlling for patient
      and injury-related variables, the commercially insured received more total
      procedures (4.30) than the uninsured (3.35) or those with Medicaid (3.34), and
      more diagnostic (2.59) procedures than the uninsured (2.03) or those with
      Medicaid (2.04). There was not a difference in the number of surgical procedures
      or medical consults among payer sources. This study noted that disparities
      (measured by the number of procedures received) compared by payer source existed
      in the care of trauma patients. However, for medical consults and definitive care
      (measured by surgical procedures), disparities were not observed. Future research
      should focus on secondary factors that influence levels of care such as patient
      level factors (health literacy) and trauma program policies.

PMID- 30185321
TI  - Incidence of Ventral Hernia Repair after Open Abdominal Aortic Aneurysm and Open
      Aortofemoral or Aortoiliac Bypass Surgery: An Analysis of 17,594 Patients in the
      State of New York.
AB  - The purpose of our study was to evaluate the rate of ventral hernia repair (VHR)
      after open abdominal aortic anneurysm in New York State compared with the rate of
      VHR after open abdominal aortic bypass procedures. The Statewide Planning and
      Research Cooperative System database was queried for all abdominal aortic
      aneurysm (AAA) and bypass procedures performed between 2000 and 2010. Social
      security death index was used to identify patients who died. The cause-specific
      Cox proportional hazard model was applied to compare the risk of having follow-up
      VHR between patients with AAA and bypass with death as a competing risk event. A
      multivariable model was used to explore independent relationship with the risk of
      having follow-up ventral hernia after adjusting for other factors. There were
      9314 patients who underwent open AAA repair, 739 (7.93%) of which had subsequent
      VHR. Comparatively, 8280 patients underwent aortofemoral or aortoiliac bypass
      procedures, with 480 (5.8%) undergoing subsequent VHR. The observed one-year,
      five-year, and 10-year VHR rates for AAA versus bypass were 2.8 versus 1.8 per
      cent, 10.0 versus 8.0 per cent, 10.7 versus 9.38 per cent, respectively. After
      controlling for all other factors, patients undergoing AAA repair were more
      likely and elderly patients were less likely to undergo VHR (P < 0.0001).
      Patients with serious comorbid conditions such as valvular disease, diabetes
      mellitus, and neurologic disorders were less likely to undergo subsequent VHR
      controlling for other factors. VHR after AAA procedures is more common compared
      with bypass procedures for occlusive disease. Because this patient population has
      significant comorbidity, prophylactic mesh placement may play a role in
      preventing necessity for future procedures.

PMID- 30185351
TI  - Stakeholder perceptions on resident-to-resident aggression: implications for
      prevention.
AB  - Objective Resident-to-resident aggression (RRA) in nursing homes is a matter of
      serious and profound concern, yet action to eliminate or mitigate RRA is hampered
      by a paucity of research. The aim of this study was to explore key stakeholders'
      knowledge and perceptions of RRA in Australian nursing homes.Methods A
      qualitative cross-sectional study design was used, and semistructured telephone
      interviews were conducted. Participants were purposively and conveniently sampled
      with replacement from a range of aged care, healthcare and legal professional
      bodies, as well as advocacy organisations. The interview contained 12 closed
      ended questions and six open-ended questions about participants' knowledge,
      experiences, perceptions and attitudes to RRA. Participant characteristics and
      responses to closed-ended questions were aggregated and proportions calculated,
      and thematic analysis was conducted by two independent researchers using a
      directed content approach.Results Fifteen participants (11 females; 73.3%) in
      senior management positions were interviewed. All were familiar with the concept
      of RRA and just over half (n = 8; 53.3%) had witnessed an incident. Major themes
      included the nature and causes of RRA and attitudes and responses to RRA.
      Potential causes of RRA included maladaptation to nursing home life, transfer of
      pre-existing issues into the nursing home environment, physical environment and
      staffing-related issues. RRA was commonly viewed by participants as dangerous and
      unpredictable or, conversely, as expected behaviour in a nursing home setting. A
      person-centred care approach was considered most effective for managing and
      responding to RRA.Conclusion The research demonstrates that understanding
      perceptions of RRA among key stakeholders is critical to identifying the nature
      and scope of the problem and to developing and implementing appropriate
      prevention strategies.What is known about the topic? RRA is common in nursing
      homes, with potentially fatal consequences for residents involved, and has
      serious implications for nursing home staff, managers, providers, and regulators.
      Despite this, the prevalence, impact, and prevention of RRA remains under
      recognised and under-researched in Australia.What does this paper add? This is
      the first Australian study to produce qualitative findings on the knowledge and
      perceptions of RRA in nursing homes among key stakeholders. This paper reports on
      the knowledge and perceptions of individuals in senior management and policy
      roles in aged care and related fields in relation to four themes: nature; causes;
      attitudes; and responses to RRA. Our findings highlight the complex and
      multifactorial nature of RRA.What are the implications for practitioners? A
      movement towards person-centred care that promotes understanding of individual
      care needs is favoured as an approach to reducing RRA. Increased reporting of
      both minor and major incidents of RRA will help to identify patterns and inform
      appropriate responses. However, a cultural shift is first required to recognise
      RRA as a manageable and preventable health care and adult safeguarding issue.

PMID- 30185352
TI  - Exploring the preferences of a culturally congruent, peer-based HIV prevention
      intervention for black men who have sex with men.
AB  - Background: HIV testing, treatment initiation and treatment adherence have been
      emphasised for Black men who have sex with men (BMSM). However, many BMSM do not
      get tested, obtain HIV treatment or adhere to treatment. It is essential to
      highlight barriers to HIV testing, treatment adherence and the ideal components
      for an intervention: peer mentors, socioeconomic resources and participant
      incentives. Methods: Five focus groups (n = 24) were conducted among HIV-negative
      and HIV-positive BMSM aged >=18 years in Los Angeles, California, USA to explore
      motivations and barriers to testing and treatment and the components of an ideal,
      culturally competent HIV testing intervention for BMSM. Results: Barriers to HIV
      testing included fear and stigma associated with discovering a HIV-positive
      status and drug use. Motivations for testing included experiencing symptoms,
      beginning new relationships, perceptions of risk and peer mentors. Conclusions:
      Future HIV prevention and treatment efforts should consider these components to
      improve health outcomes among BMSM.

PMID- 30185353
TI  - Analysis of uncertainty in the surgical department: durations, requests and
      cancellations.
AB  - Objective Analytical techniques are being implemented with increasing frequency
      to improve the management of surgical departments and to ensure that decisions
      are well informed. Often these analytical techniques rely on the validity of
      underlying statistical assumptions, including those around choice of distribution
      when modelling uncertainty. The aim of the present study was to determine a set
      of suitable statistical distributions and provide recommendations to assist
      hospital planning staff, based on three full years of historical data.Methods
      Statistical analysis was performed to determine the most appropriate
      distributions and models in a variety of surgical contexts. Data from 2013 to
      2015 were collected from the surgical department at a large Australian public
      hospital.Results A log-normal distribution approximation of the total duration of
      surgeries in an operating room is appropriate when considering probability of
      overtime. Surgical requests can be modelled as a Poisson process with rate
      dependent on urgency and day of the week. Individual cancellations could be
      modelled as Bernoulli trials, with the probability of patient-, staff- and
      resource-based cancellations provided herein.Conclusions The analysis presented
      herein can be used to ensure that assumptions surrounding planning and scheduling
      in the surgical department are valid. Understanding the stochasticity in the
      surgical department may result in the implementation of more realistic decision
      models.What is known about the topic? Many surgical departments rely on crude
      estimates and general intuition to predict surgical duration, surgical requests
      (both elective and non-elective) and cancellations.What does this paper add? This
      paper describes how statistical analysis can be performed to validate common
      assumptions surrounding surgical uncertainty. The paper also provides a set of
      recommended distributions and associated parameters that can be used to model
      uncertainty in a large public hospital's surgical department.What are the
      implications for practitioners? The insights on surgical uncertainty provided
      here will prove valuable for administrative staff who want to incorporate
      uncertainty in their surgical planning and scheduling decisions.

PMID- 30185354
TI  - Using subcutaneous methotrexate to prolong duration of methotrexate therapy in
      rheumatoid arthritis.
AB  - OBJECTIVE: Our study aims to determine whether the use of subcutaneous
      methotrexate (SC MTX) is associated with prolonged MTX use and lower incidence of
      hepatotoxicity in rheumatoid arthritis (RA) patients on MTX monotherapy and
      multiple drug therapy. METHODS: We conducted a retrospective cohort study using
      national databases of a large hospital system. Subjects had been diagnosed with
      RA and treated with MTX between September 30, 1999, and October 1, 2009. Outcomes
      of interest were the amount of time on MTX monotherapy or multiple disease
      modifying anti-rheumatic drug (DMARD) therapy before addition of additional
      DMARDs or biologic agents, respectively. We conducted Cox regressions and Kaplan
      Meier curves for association between SC MTX use and length of time before
      therapeutic change. We conducted chi-square tests for association between SC MTX
      use and elevated liver function tests (LFT). RESULTS: MTX monotherapy: SC MTX was
      associated with a significantly lower likelihood of therapeutic change (HR 0.64,
      95% CI 0.52-0.78). Multiple DMARD therapy: SC MTX was not associated with a lower
      risk of adding a biologic (HR 1.13, 95% CI 0.97-1.31). Liver enzymes: There was
      no significant association between use of SC MTX and decreased frequency of
      abnormal LFTs [p=0.09 for alanine aminotransferase (ALT), p=0.924 for aspartate
      aminotransferase (AST)]. CONCLUSION: Use of SC MTX is associated with longer
      duration of MTX monotherapy before addition of other DMARDs/biologic agents in RA
      patients. Use of SC MTX is not associated with significantly longer duration of
      multiple DMARD therapy before addition of biologic agents. Use of oral MTX is not
      significantly associated with increased frequency of elevated LFTs.

PMID- 30185355
TI  - Infodemiology of antiphospholipid syndrome: Merging informatics and epidemiology.
AB  - OBJECTIVE: To investigate trends in Internet search volumes linked to
      Antiphospholipid Syndrome (APS), using Big Data monitoring and data mining.
      METHODS: Based on the large amount of data generated by Google Trends and
      scientific search tools (SCOPUS, Medline/Pubmed, and ClinicalTrails.gov), we
      performed a longitudinal analysis based on the term "antiphospholipid" in a 5
      year web-based research. RESULTS: Google Trends captured that APS-related digital
      interest was generally steady in the study period (Relative Search Volume [RSV]
      mean value 71.1+/-9.3% [95%CI 55.6-89.4], median 72.0), with no significant peak
      based on different seasons (e.g. winter vs. summer time). When comparing the APS
      related digital interest with search volumes generated in the same time period
      for Inherited Thrombophilias (IT) and Systemic Lupus Erythematosus (SLE), we
      found a digital interest 35-times higher for APS than for IT (RSV mean value
      71.1+/-9.3% [95%CI 55.6-89.4] vs. 2+/-3.2% [95%CI 0.7-7.4]). When compared to
      SLE, APS reached a similar RSV, showing a comparable digital interest (RSV mean
      value 71.1+/-9.3% [95%CI 55.6-89.4] vs. 87+/-11.8% [95%CI 60.7-107.9]). When
      adjusting for relative search volumes of Google Trends, we found a relative
      prevalence of search volumes of 35.5% in Europe, 12.3% in the United States,
      11.5% in South America, 11.2% in Australia, 9.2% in Canada, 9.2% in Japan, and
      5.1% in India. We observed an overall similar distribution of search volumes from
      Google Trends compared to results from Medline/Pubmed, SCOPUS, and
      ClinicalTrials.gov. In brief, the United States and Europe (mainly Italy, the
      United Kingdom, Spain, France, and Germany) presented the higher RSV. Similarly,
      these countries showed a higher number of research publications and on-going
      trials in the field of APS. CONCLUSION: In this study, we demonstrated that the
      interest in APS is not equally distributed globally. Thus, geopolitical
      differences might represent a challenge when attempting to estimate the
      prevalence of APS or designing worldwide investigations in APS. Combining the
      expanding framework of infodemiology with scientific networking collaborative
      efforts, such as AntiPhospholipid Syndrome Alliance For Clinical Trials and
      InternatiOnal Networking (APS ACTION), will help better define the syndrome in
      terms of prevalence, event occurrence ratios, and thrombosis risk assessment.

PMID- 30185356
TI  - The impact of intra-articular injection of diprospan at the knee joint on blood
      glucose levels in diabetic patients.
AB  - OBJECTIVE: To evaluate the effect of intra-articular (IA) corticosteroid
      injection (IACI) of betamethasone dipropionate/betamethasone sodium phosphate
      (Diprospan) on blood glucose levels in diabetic patients METHODS: Patients with
      type 2 diabetes and symptomatic osteoarthritis of the knee (OAK) in whom medical
      therapy failed were administered 1 mL Diprospan IACI (5 mg of betamethasone
      dipropionate +2 mg of betamethasone sodium phosphate). Patients were asked to
      monitor blood glucose levels before and 2 h after meals for 1 week before and 12
      days after the injection was administered. A control group was administered an IA
      injection of hyaluronic acid. RESULTS: Twelve patients from the Diprospan group
      and six from the control group were recruited for the study. Patients in the
      Diprospan group had significantly increased blood glucose levels with median
      initial and peak levels of 187.5 mg% and 310 mg%, respectively, at a median of 4
      and 11.5 h following IACI, respectively. The last peak level was seen after a
      median of 45 h following IACI. There was no significant increase in blood glucose
      levels in the control group. CONCLUSION: Diprospan IACI is associated with
      significantly increased blood glucose levels in all diabetic patients with OAK.

PMID- 30185357
TI  - Safety of retrievable inferior vena cava filters in patients with the
      antiphospholipid syndrome.
AB  - OBJECTIVE: Consideration for placement of an inferior cava filter arises in
      patients with APS where cessation of anticoagulation is necessary or thrombotic
      complications continue despite maximal anticoagulation. Permanent IVC filters are
      recommended to be avoided. We evaluated the safety of placement and removal of
      retrievable inferior vena cava filters in patients with APS. METHODS: Case series
      of 5 patients with APS and aPL antibodies who had placement and removal of
      retrievable IVC filter (because of contraindication to anticoagulation or ongoing
      thrombosis despite full anticoagulation) to assess for safety, presence of clots
      in the vena cava or on the filter while in the body, evidence of PE, or clot on
      the explanted filter. RESULTS: Insertion and removal, even while on
      anticoagulation, was safe. There was no evidence of clot in the vena cava, on the
      filter or pulmonary embolism in all cases. CONCLUSION: Where necessary,
      retrievable IVC filters may be safer in APS patients but should not be left in
      for long periods of time.

PMID- 30185358
TI  - Evidence of peripheral large nerve involvement in fibromyalgia: a retrospective
      review of EMG and nerve conduction findings in 55 FM subjects.
AB  - OBJECTIVE: Whereas small fiber neuropathy (SFN) is now a recognized part of
      fibromyalgia (FM), surprisingly little attention has been paid to any findings of
      large fiber neuropathy (LFN) in this disorder. Since 90% to 95% of FM subjects
      seen in our outpatient facility routinely undergo EMG and nerve conduction
      studies (NCS) we elected to retrospectively review the EMG/NCS results garnered
      from a large cohort of unselected subjects in order to describe the
      electrodiagnostic features of LFN in FM. METHODS: Records from 100 consecutive,
      unselected clinic patients meeting the 1990 ACR criteria for FM, who had
      undergone EMG/NCS, were reviewed. The same electromyographer tested all subjects.
      After exclusion of FM patients with any other clinically relevant condition that
      might influence EMG results (e.g., familial neural degenerative conditions,
      diabetes mellitus, Vitamin B-12 deficiency, etc.) fifty-five FM subjects
      remained: 29 subjects with "FM Only," and 26 subjects with FM+Rheumatoid
      Arthritis ("FM+RA"). All subjects had also undergone ankle area skin biopsy for
      determination of epidermal nerve fiber density (ENFD). Fourteen other subjects,
      without FM or RA, examined by the same electromyographer, were used as an EMG/NCS
      comparison group. RESULTS: Ninety percent of the "FM Only" subjects demonstrated
      a demyelinating and/or axonal, sensorimotor polyneuropathy, and 63% had findings
      of SFN (ENFD <=7 fibers/mm), suggesting a mixed fiber neuropathy in most.
      Furthermore, 61% of the "FM Only" subjects showed EMG findings suggestive of non
      myotomal lower extremity axonal motor denervation, most likely due to a
      polyneuropathy, and 41% satisfied published criteria for "possible" chronic
      inflammatory demyelinating polyneuropathy (CIDP). There was surprisingly little
      difference in the EMG/NCS findings between the "FM Only" and the "FM+RA" groups.
      With the exception of carpal tunnel syndrome, our EMG/NCS comparison group showed
      few to none of these findings. CONCLUSION: Our review of the EMG/NCS results,
      gleaned from the largest FM cohort yet studied with these modalities, shows that
      electrodiagnostic features of polyneuropathy, muscle denervation, and CIDP are
      common in FM. Furthermore these electrodiagnostic findings are often seen
      coincident with SFN, and are not significantly influenced by the presence of RA.
      These results, particularly when taken as a whole, suggest that EMG/NCS may be
      clinically useful in detecting LFN in FM and help in better understanding the
      etiopathogenesis of this painful disorder.

PMID- 30185359
TI  - A study on characteristics of rheumatoid arthritis patients achieving remission
      in depression with 6 months of bDMARDs treatment.
AB  - OBJECTIVE: To investigate the relationship between baseline factors and
      depression remission after a 6-month biological disease-modifying antirheumatic
      drugs (bDMARDs) treatment in rheumatoid arthritis (RA) patients. METHODS: The
      study was conducted in 152 RA patients treated with bDMARDs. The following
      patient's characteristics were studied: gender, age, disease duration, baseline
      prednisolone dosage, and serum matrix metalloproteinase3 (MMP3) levels. For
      assessment, we used the simple disease activity index (SDAI) for RA disease
      activity, Health Assessment Questionnaire Disability Index (HAQ-DI) for
      activities of daily living (ADL), Short Form-36 for nonspecific health-related
      quality of life (QOL), and Hamilton Depression Rating Scale (HAM-D) scores for
      the depression status. Depressed remission was clarified using HAM-D <=7 after 6
      months of treatment. The patients were divided into two groups according to the
      presence or absence of depression, and a retrospective study was conducted.
      RESULTS: Based on binominal logistic analyses, RA patients' with depression
      remission (n=124) compared to those without depression remission (n=28) had a
      younger age (p=0.0045, odd ratio: 0.94, 95% confidence interval [CI]:0.8-0.98),
      female sex (p=0.021, odd ratio:0.21, 95% CI:0.054-0.79), and lower HAM-D scores
      (p=0.0073, odd ratio:0.85, 95% CI:0.76-0.96) CONCLUSION: It was proposed that RA
      patients who are females, younger in age, and have lower depressed scores at
      baseline can achieve a depression remission status with the bDMARDs treatment.

PMID- 30185360
TI  - Serum sCTLA-4 levels and clinical manifestations in ankylosing spondylitis
      patients.
AB  - OBJECTIVE: T cell abnormal activation is thought to have a main role in the
      etiology of ankylosing spondylitis (AS). While cytotoxic T lymphocyte-associated
      molecule-4 (CTLA-4) is suppressing the immune system, in previous studies serum
      soluble CTLA-4 (sCTLA-4) was detected at high amounts in autoimmune disorders. We
      sought to evaluate the association between soluble CTLA-4 in serum and disease
      activity in AS patients. METHODS: Thirty-eight patients with AS, 28 rheumatoid
      arthritis (RA) patients, and 27 disease-free controls were enrolled to the study.
      The levels of sCTLA-4 were determined for each participant using an enzyme-linked
      immunosorbent assay. The erythrocyte sedimentation rate (ESR), C-reactive
      peptide, and demographic characteristics were documented. The data were analyzed
      by using relevant statistical methods. RESULTS: In comparison with RA patients
      and controls, patients with AS showed high sCTLA-4 levels (p<0.001). The sCTLA-4
      levels did not correlate with the severity of the disease in AS patients
      (p=0.370). The ESR levels and Bath Ankylosing Spondylitis Disease Activity Index
      were correlated in AS patients (p=0.012). CONCLUSION: We evaluated the
      association between the disease severity of AS and sCTLA-4. Although, the
      correlation was not shown, sCTLA-4 was highest in the AS group. Further studies
      with larger samples should be completed to attain a better understanding of the
      AS etiology.

PMID- 30185362
TI  - Epithelioid myxofibrosarcoma developing at the injection site of Adalimumab
      therapy for psoriatic synovitis.
AB  - The interplay between inflammation and cancer is the subject of intense interest.
      The recent approval of a number of checkpoint inhibitors has opened novel
      therapeutic pathways for several cancers. Conversely, biologic suppressors of
      inflammation, such as Tumor Necrosis Factor (TNF) inhibitors, have been utilized
      over the past two decades for the management of chronic inflammatory autoimmune
      diseases. While the overall rates of malignancy in patients using anti TNF
      therapies are not elevated, increased risk has been established for cutaneous
      malignancy, particularly carcinoma. In subsets of patients, such as those with
      rheumatoid arthritis, a modestly increased incidence of melanoma is also
      documented. Herewith, we present the first reported instance of a sarcoma of the
      dermis and superficial subcutaneous tissue at the injection site of Adalimumab in
      a woman being treated for psoriatic synovitis. We review the literature and
      suggest that a more nuanced documentation of adverse events is needed to clarify
      the iatrogenic risk of rare cancers, such as soft tissue sarcomas, in patients
      taking these biological therapies.

PMID- 30185361
TI  - Outcomes of rituximab therapy in refractory lupus: A meta-analysis.
AB  - OBJECTIVE: Conventional treatment of systemic lupus erythematosus (SLE) and lupus
      nephritis (LN) is associated with damage accrual, hence increased morbidity rate.
      Off-label use of rituximab (RTX) has shown significant promise in this patient
      group; however, data are still controversial. We aimed to analyze the outcomes of
      RTX therapy in refractory lupus using a meta-analysis approach. METHODS:
      Electronic search of the medical literature was conducted using a combination of
      relevant keywords to retrieve studies on the safety and efficacy of RTX in SLE
      and LN patients. Results were screened against our inclusion and exclusion
      criteria and two reviewers independently extracted the data for analysis.
      Comprehensive meta-analysis software was used to pool the data from individual
      studies and provide summary effect estimates. RESULTS: Thirty-one studies that
      enrolled 1112 patients were finally eligible for the meta-analysis. The overall
      global, complete, and partial response rates to RTX therapy were 72%, 46%, and
      32%, respectively. RTX significantly decreased Systemic Lupus Erythematosus
      Disease Activity Index (SLEDAI) and British Isles Lupus Activity Group (BILAG)
      scores (p<0.001). Prednisone dose was significantly reduced after RTX treatment
      in both SLE and LN groups (p<0.001), and proteinuria was lowered in SLE (p<0.001)
      than in LN patients (p=0.07). Infection and infusion-related reactions were the
      most common side effects. CONCLUSION: RTX therapy in refractory SLE and LN
      patients proved clinical efficacy and favorable safety outcomes. Larger well
      designed randomized clinical trials are warranted.

PMID- 30185363
TI  - Azathioprine-induced interstitial nephritis in an anti-neutrophil cytoplasmic
      antibody (ANCA) myeloperoxidase (MPO) vasculitis patient.
AB  - Azathioprine (AZA) is used in a wide array of autoimmune diseases, still
      corresponding to the mainstay maintenance therapy in anti-neutrophil cytoplasmic
      antibody (ANCA)-associated vasculitides. Although generally well-tolerated,
      several side effects are recognized. We report the case of a 50-year-old
      Caucasian man with kidney-limited ANCA myeloperoxidase (MPO) vasculitis who
      presented with general malaise, fever, worsening renal function, and elevated
      inflammatory markers 2 weeks after the initiation of therapy with oral AZA.
      Although a disease relapse was suspected, renal biopsy revealed an eosinophilic
      infiltrate, suggestive of acute interstitial nephritis. After suspension of AZA,
      a sustained improvement of renal function and normalization of inflammatory
      markers was observed. A diagnosis of allergic interstitial nephritis secondary to
      AZA was established, corresponding to the first biopsy-proven case described in
      an ANCA MPO vasculitis patient. Although rare, renal toxicity of AZA must be
      present in the clinician's mind, avoiding the straightforward assumption of
      disease relapse in the case of worsening renal function.

PMID- 30185364
TI  - Muscle weakness as a presenting symptom in ANCA-associated vasculitis.
AB  - Muscle weakness is rarely a presenting symptom of anti-neutrophil cytoplasmic
      antibody (ANCA)-associated vasculitis (AAV), although the disease frequently
      involves the lungs, skin, neurons, and kidneys. Here we describe a case of AAV
      presenting with muscle weakness in which only muscle biopsy could confirm the
      diagnosis. The literature review, including three similar cases, suggested that
      patients with ANCA-associated muscle vasculitis likely had myalgia, normal levels
      of creatine kinase, pulmonary fibrosis, rheumatoid factor, and muscle edema on
      MRI.

PMID- 30185365
TI  - Sternoclavicular joint arthritis as the initial presentation of sarcoidosis.
AB  - Sarcoidosis is a multisystem granulomatous disease of unknown etiology. It can
      affect the musculoskeletal system in the form of acute and rarely, in the form of
      chronic peripheral arthritis involving bilateral small and large joints. Axial
      joint involvement with sarcoidosis is rare. Herein we report a case with
      sternoclavicular joint arthritis as the initial presentation of sarcoidosis. This
      report aims to demonstrate a rare initial presentation of sarcoidosis and
      highlight the importance of considering sarcoidosis as a differential diagnosis
      in patients presenting with sternoclavicular joint arthritis.

PMID- 30185367
TI  - Oral treatment of osteoarticular infections caused by Kingella kingae in
      children.

PMID- 30185366
TI  - Upper extremity venous thrombosis associated with primary antiphospholipid
      syndrome and immunoglobulin M nephropathy in diabetes mellitus type II.
AB  - Antiphospholipid syndrome (APS) is a disorder characterized by antiphospholipid
      antibody positivity, arterial or venous thrombosis, and fetal loss. In APS, renal
      as well as vascular and glomerular involvement is observed. Systemic lupus
      erythematosus and other connective tissue diseases should be excluded to diagnose
      primary APS. Immunoglobulin M (IgM) nephropathy is characterized by single or
      dominant IgM deposition in glomerular mesangium. It often presents with hematuria
      and proteinuria. In a 45-year-old female patient admitted to our clinic with
      diabetes mellitus and proteinuria, fundus examination did not reveal diabetic
      retinopathy but a high anticardiolipin IgM and venous thrombosis in the upper
      extremity were observed. Renal biopsy revealed IgM nephropathy. The patient was
      diagnosed with primary APS and IgM nephropathy. Cyclophosphamide and steroid
      treatment was started. Her proteinuria decreased as a result of the treatment.
      Although, it is reported in the literature that primary APS coexists with other
      glomerulonephritis, we did not detect coexistence of primary APS and IgM
      nephropathy.

PMID- 30185368
TI  - Gouty tophi with purpura in a patient with ischemic heart disease and acute
      kidney injury.

PMID- 30185369
TI  - Hypertrophic osteoarthropathy: Detecting periosteal inflammation using Doppler
      ultrasound.

PMID- 30185371
TI  - Is rheumatoid arthritis an innocent bystander in female reproductive problems? A
      comparative study of fertility in Nigerian women with and without rheumatoid
      arthritis.
AB  - OBJECTIVE: Contrary to the old belief that rheumatoid arthritis (RA) is rare in
      sub-Saharan Africa, recent reports have increasingly recognized that the burden
      of the disease has probably been long under-appreciated in West Africa. Thus,
      fertility and other attributes of the reproductive lives among women with RA have
      not received research attention in Africa. We aimed to compare the fertility
      between married Nigerian women with and without RA. METHODS: A comparative study
      of 50 women with RA and 50 women without RA was conducted via the specialist
      rheumatology clinics at two teaching hospitals in Nigeria. The participants were
      aged 18 years or older. Patients with RA were recruited on the basis of the
      fulfillment of the 1987 American College of Rheumatology classification criteria
      for RA, whereas the control participants were age-matched to the patients. Using
      an interviewer-administered questionnaire, demographic and clinical information
      was collected from each participant. Clinical details at the time of diagnosis of
      RA were extracted from the hospital records of the patients. The patients were
      tested for rheumatoid factor and anti-cyclic citrullinated peptide antibody, and
      the disease activity was assessed using the Clinical Disease Activity Index. The
      functional status was determined using the Steinbrocker functional
      classification. Statistical analysis was performed using Statistical Package for
      Social Sciences (SPSS) version 20 (IBM Corp.; Armonk, NY, USA). The proportions
      of individuals with history of infertility, irregular menstruation, and
      menopausal states were compared between the two groups using chi2 and Fisher's
      exact tests, whereas the durations of infertility and parities were compared
      using Mann-Whitney U and independent t-tests, respectively. RESULTS: A positive
      history of infertility was found in 22 (44%) patients and 14 (28%) controls
      (p=0.096), while 17 (34%) patients and 23 (46%) controls were found to be
      postmenopausal (p=0.221). History of irregular menstruation was present in 15
      (30%) patients and 4 (8%) controls (p=0.005). The median duration of infertility
      was 60 (range: 16-132) months among the patients and 36 (range: 12-72) months
      among the controls (p=0.036), while the mean parity was 2.85+/-1.8 among the
      patients and 3.77+/-2.2 among the controls (p=0.027). A significant association
      was found between infertility and functional class as well as methotrexate
      treatment. CONCLUSION: Infertility is not uncommon among patients with RA, and
      like many aspects of rheumatic diseases, it may have been under-recognized in the
      Nigerian patients.

PMID- 30185370
TI  - Catalytic antibodies in patients with systemic lupus erythematosus.
AB  - OBJECTIVE: Antibodies with catalytic (hydrolytic) properties to DNA or RNA have
      been reported in systemic lupus erythematosus (SLE). However, it is well known
      that ethnicity plays an important role in the presentation of SLE and severity of
      the disease; hence, these data may not truly represent a general feature of all
      SLE patients. Therefore, we have analyzed the hydrolyzing activity of
      immunoglobulin G (IgG) of SLE patients from the Indian population with an aim to
      decode whether the catalytic antibody response represents part of an active
      disease process. METHODS: IgGs were isolated from the sera of 72 consecutive
      patients diagnosed with SLE. As a control, IgGs from healthy donors were used.
      The catalytic activity of IgG was measured by PFR-MCA and affinity-linked
      oligonucleotide nuclease assay. RESULTS: IgGs from patients with SLE from the
      Indian subcontinent displayed significantly higher hydrolysis rates of both the
      surrogate substrate, PFR-MCA, and the DNA than IgG from healthy individuals.
      Intergroup comparisons of the IgG-PFR-MCA interactions with clinical
      manifestations of the disease demonstrated a significantly increased level of
      hydrolysis among the patients with renal involvement who tested positive for anti
      dsDNA antibodies. The PFR-MCA hydrolysis also appears to be associated with the
      active disease (p=0.0988, vs. inactive group). CONCLUSION: The prevalence of
      catalytic antibodies represents a general feature of SLE patients, irrespective
      of their origin.

PMID- 30185373
TI  - Fixation of unstable ankle fractures using a long hindfoot nail.
AB  - BACKGROUND: Management of fragility fractures of the ankle is challenging. Non
      operative treatment often requires significant periods of reduced weight bearing.
      Operative fixation is difficult due to osteoporotic bone and poor soft tissues.
      The aim of this study was to review the initial experience of treating unstable
      ankle fractures with a retrograde femoral nail used as a long tibiotalocalcaneal
      nail. PATIENTS AND METHODS: Sixteen patients were treated from January 2014 until
      November 2017. Mean age was 73 (50-96) and twelve of the sixteen patients were
      female. All patients had three or more co-morbidities and an American Society of
      Anaesthesiologists score of 3. All patients had unstable ankle fracture
      configurations and were classified using the AO classification. RESULTS: All
      patients regained baseline mobility by final follow-up (mean 21 months follow
      up). Four of the sixteen patients died within 12 months of surgery. There were no
      wound complications or deep infections. There were no cases of metalwork failure
      or peri-prosthetic fracture. DISCUSSION: Use of a retrograde femoral nail has
      been shown to be a safe and effective option in the management of unstable ankle
      fractures in elderly and frail patients. This technique may lead to lower wound
      complications compared to traditional fixation techniques and allows earlier
      mobilisation.

PMID- 30185374
TI  - Empowering the Aging with Mobile Health: A mHealth Framework for Supporting
      Sustainable Healthy Lifestyle Behavior.
AB  - Healthcare providers are shifting to a value-based model that acknowledges the
      importance of a healthy lifestyle for managing chronic disease and mental health.
      This approach empowers patients to adopt and/or sustain healthy lifestyle choices
      through the use of innovative technologies-providing beneficial ways of
      delivering health literacy, self-monitoring, and patient-provider collaboration.
      Such pathways have the potential to enable healthy lifestyle management for a
      growing U.S. cohort-the "baby boomer" generation (BBG)-who are at risk for
      developing heart disease, stroke, arthritis, high cholesterol, and diabetes, etc.
      In this paper, we argue for a new mHealthy lifestyle management (MLM) model that
      uses mobile health technology as a means to engage BBG consumers in ways that
      establish their role in self-care and decision-making, as well as patient
      provider collaboration that can significantly impact sustainable healthy
      lifestyle behaviors. By merging the domains of health informatics and human
      factors psychology, MLM addresses the complex challenges associated with patient
      provider collaborative work, while offering a healthcare framework to BBGs in
      their quest to self-manage a physical and/or mental healthy lifestyle. A MLM use
      case highlights the challenges and solutions for team-based clinical counseling.
      Finally, recommendations for future MLM tools are outlined that support patient
      access to personal health eTools, information, and services.

PMID- 30185372
TI  - Risk factor assessment of rheumatoid arthritis in North Kerala.
AB  - OBJECTIVE: Rheumatoid arthritis (RA) is a multifactorial disease; it leads to
      disabling and painful chronic inflammatory arthritis. Its onset may be delayed or
      even prevented by modifying the risk factors involved. Many genetic, epigenetic,
      and environmental factors are implicated in the pathogenesis of RA. The
      objectives of this case-control study were to assess various risk factors in our
      population and to compare the same with age- and sex-matched controls. METHODS:
      We studied 118 cases with RA diagnosed using the EULAR criteria. In total, 581
      age- and sex-matched controls were selected. Each individual was administered a
      separate questionnaire regarding their risk factors (known risk factors were
      studied). The implicated dietary factors were incorporated in a food frequency
      questionnaire (FFQ) and administered to both cases and controls. Comparison was
      made between those who consume an item at a particular frequency, who consume
      less, and who consume nothing at all. Among those who consume, each group was re
      compared. Statistical analysis was conducted using Statistical Package for Social
      Sciences (IBM Corp.; Armonk, NY, USA). RESULTS: There was significant
      relationship for family history, periodontitis, history of chikungunya, and sun
      exposure (p<0.05). Association with various food items was studied using the FFQ,
      but the relationship was inconsistent, probably due to consumption of modified
      diet by the persons with RA. Also, a majority of cases were females and
      nonsmokers for assessing an association with smoking habits. CONCLUSION: In our
      population, previous infections (e.g., chikungunya and poor oral hygiene with
      periodontitis) were the prominently observed risk factors. Also, smoking was less
      common among women, and probably contributed less, as majority of cases were
      females. For dietary pattern association, a prospective cohort study may be
      needed.

PMID- 30185375
TI  - Women's ecofeminist spirituality: Origins and applications to psychotherapy.
AB  - The aim of this paper is to theoretically explore the origins and possible
      psychotherapeutic applications of some neo-pagan, neo-shamanic, or psycho
      spiritual women's movements that are currently spreading in Western countries. In
      spite of their great diversity, they are all encompassed within the term
      "ecofeminist spirituality." This article analyzes their ideological, historical,
      and cultural origins, placing special emphasis on their psychotherapeutic role
      and describing the main tools and fields of application.

PMID- 30185376
TI  - Pediatric penile surgery by a nurse practitioner in the operating room.
AB  - INTRODUCTION: With the growing shortage of pediatric urological surgeons, it was
      our aim to streamline our system to get patients with less complex penile
      procedures performed in a timely manner. To do this, an advanced practice
      provider (APP) was trained to perform minor penile procedures in children in the
      operating room(OR). OBJECTIVES: The goal of our study was to show that with
      proper training an APP could safely perform a circumcision in the OR. STUDY
      DESIGN: After approval of the study center's credentialing committee, a NP was
      trained to perform revisions and initial circumcisions in children in the OR. The
      process involved: (1) observation, (2) first assisting and (3) performing the
      procedure with direct, and later in-direct, supervision. The first 100 cases were
      evaluated for surgical complications, post-operative complications and return
      rates to the OR. RESULTS: 100 independent cases were completed with 90 having
      only in-direct supervision. There were no operative complications, nor any
      documented emergency room or urgent care visits in the immediate post-operative
      period. There were no early returns to the OR and only 1 scheduled follow-up
      procedure for a penile skin bridge. DISCUSSION: It was demonstrated that with
      proper training a NP can safely perform minor penile procedures in the OR. This
      allows us to free up our pediatric urology physicians to see and operate on more
      complex pediatric urology problems. In addition, it allows those with minor
      penile issues to be cared for more expeditiously. A concern related to training
      NPs to do circumcisions could be the loss of control by urologists. In this
      situation, the attending physician is ultimately responsible from a medico-legal
      standpoint. That would not be true if the NP was practicing independently. With a
      shortage of urologists, this significantly expands the ability to care for our
      patient population. In additional, attending surgeons will have a greater freedom
      to perform major procedures. A limitation of the study was that a patient
      satisfaction survey was not obtained to see if there were concerns over a APP
      doing their circumcision. Personal feedback on 30 of the patients that did not
      return for the follow-up visit was not obtained. The authors of the study are
      primary providers of pediatric urology care in the study region, thus any
      individual with concerns would have been referred. CONCLUSIONS: It was
      demonstrated that a well-trained APP can safely perform minor penile procedures
      independently in the OR with indirect supervision.

PMID- 30185377
TI  - Does postoperative irradiation improve survival in early-stage endometrial
      cancer?
AB  - Endometrial cancer is the most common gynecological cancer in developed
      countries. Postoperative irradiation has been shown to lower locoregional
      relapses among high-intermediate risk endometrial cancer patients. In addition,
      vaginal cuff brachytherapy has demonstrated similar control to external beam
      radiotherapy but with lower toxicity. Although randomized trials have failed to
      translate that into better overall survival, reports from large databases, such
      as the National Cancer Database and the Surveillance, Epidemiology, and End
      Results database, have shown evidence of a statistical relationship between
      postoperative irradiation and survival in the intermediate- and high-risk groups.
      This review will address the risk groups that have led the therapeutic decisions
      and then we will review the clinical results accordingly. Special attention will
      be paid to the survival results based on the data presented through an analysis
      of the large databases that suggest a possible survival benefit.

PMID- 30185378
TI  - Patients' perceived health information needs in inflammatory arthritis: A
      systematic review.
AB  - OBJECTIVES: To identify the breadth of the literature regarding patients'
      perceived health information needs related to inflammatory arthritis care.
      METHODS: A systematic scoping review of MEDLINE, EMBASE, CINAHL and PsycINFO was
      performed to identify relevant articles (1990 -2016) examining patients'
      perceived needs relating to health information in inflammatory arthritis. Data
      and themes were identified and categorised and risk of bias assessed. RESULTS:
      Twenty nine studies (11 quantitative, 14 qualitative and 4 mixed methods) from
      4121 identified articles were relevant for inclusion. Most focussed on rheumatoid
      arthritis. Key findings included: (1) Reasons for seeking health information
      often focussed on gaining ownership over their condition and facilitating self
      management. (2) Demographic differences in information needs were inconsistent,
      but women and younger patients generally reported more needs. (3) Desired
      information content was broad, and included targeted and practical information
      covering disease treatment and psychosocial wellbeing. (4) Preferred information
      delivery method was consultation with a Rheumatologist; however group sessions
      had advantages for psychosocial issues while written information provided useful
      supplementation. (5) Barriers to meeting health information needs were around
      timely access. CONCLUSIONS: Patients with inflammatory arthritis have high
      information needs, desiring practical and individualised information. When
      developing strategies to meet patients' information needs, aligning patient
      expectations with delivery methods that are accessible, cost-effective and
      flexible may help to optimize patient outcomes.

PMID- 30185379
TI  - Efficacy and safety of biological agents in the older rheumatoid arthritis
      patients compared to Young: A systematic review and meta-analysis.
AB  - OBJECTIVE: Biologic anti-rheumatic drugs are used with less frequency among older
      patients compared to young patients. This population is less represented in
      studies performed to evaluate the efficacy and safety of this drugs. We aimed to
      assess the efficacy and safety of biological agents between the older RA patients
      compared to young. METHODS: A comprehensive, systematic search was conducted in
      major indexing databases using key terms for RA and each biological agent. The
      review process was completed by 2 investigators. Both randomized controlled
      trials and observational studies of at least 6-month duration conducted in adult
      RA patients were included. Outcomes of interest were clinical efficacy and
      safety. Effect-estimates were pooled using random-effects modeling if 4 or more
      studies used the same scale and time-frame for measuring outcomes. RESULTS: 24
      studies (16 focusing on anti-TNF agents) representing 63,705 patients (24% were
      older) were included. Older RA patients had worse baseline RA disease activity,
      longer disease duration at the time of enrollment in the trial (14.4 +/- 3.6 vs.
      10.9 +/- 3.6 years; p < 0.001) and higher steroid use (73.2 vs. 64.7%, p < 0.001)
      than younger. 5 out of 6 studies assessing anti-TNF agents showed worse efficacy
      outcomes in older patients. The pooled OR of infection and ADRs with anti-TNF
      agents in older compared to young RA patients was OR 1.59 (95% CI: 1.45-1.76) and
      1.40 (95% CI: 1.23-1.61) respectively. CONCLUSIONS: Older patients had worse
      safety and efficacy with biological agents but also had worse baseline disease
      activity. There was significant heterogeneity in reporting outcomes and very
      limited studies in biological agents other than anti-TNF drugs.

PMID- 30185380
TI  - Lysosomes nor Mice Move Forward without Borcs7.
AB  - Lysosome function and position in the cytoplasm depends on the BORCS machinery,
      which tethers lysosomes to the kinesin microtubule motor. A recent paper of
      Snouwaert et al. in Cell Reports characterizes a mouse with a spontaneous
      mutation in the Borcs7 subunit, which causes axonal dystrophy and impaired motor
      function.

PMID- 30185382
TI  - Nursing considerations and interdisciplinary coordination in the care of
      conjoined twins.
AB  - Traditional nursing care strategies may require modification to meet the unique
      needs of conjoined twins. Here we discuss the strategies found to be useful in
      planning for and responding to distinctive circumstances encountered throughout
      hospitalization, as well as lessons learned. Areas of focus include ensuring
      privacy, designing adequate unit accommodations to meet space and equipment
      needs, staffing considerations and adaptations to typical neonatal intensive care
      nursing interventions. The utility of a team-based approach to interdisciplinary
      care coordination is also discussed. With adequate preparation and thoughtful
      innovation, most tertiary neonatal intensive care units can readily adapt to the
      unique needs of conjoined twins.

PMID- 30185383
TI  - Development of a Novel Global Surgery Course for Medical Schools.
AB  - OBJECTIVE: We endeavored to create a comprehensive course in global surgery
      involving multinational exchange. DESIGN: The course involved 2 weeks of
      didactics, 2 weeks of clinical rotations in a low-resource setting and 1 week for
      a capstone project. We evaluated our success through knowledge tests, surveys of
      the students, and surveys of our Zimbabwean hosts. SETTING: The didactic portions
      were held in Sweden, and the clinical portion was primarily in Harare with
      hospitals affiliated with the University of Zimbabwe. PARTICIPANTS: Final year
      medical students from Lund University in Sweden, Harvard Medical School in the
      USA and the University of Zimbabwe all participated in didactics in Sweden. The
      Swedish and American students then traveled to Zimbabwe for clinical work. The
      Zimbabwean students remained in Sweden for a clinical experience. RESULTS: The
      course has been taught for 3 consecutive years and is an established part of the
      curriculum at Lund University, with regular participation from Harvard Medical
      School and the University of Zimbabwe. Participants report significant
      improvements in their physical exam skills and their appreciation of the needs of
      underserved populations, as well as confidence with global surgical concepts. Our
      Zimbabwean hosts thought the visitors integrated well into the clinical teams,
      added value to their own students' experience and believe that the exchange
      should continue despite the burden associated with hosting visiting students.
      CONCLUSIONS: Here we detail the development of a course in global surgery for
      medical students that integrates didactic as well as clinical experiences in a
      low-resource setting. The course includes a true multilateral exchange with
      students from Sweden, the United States and Zimbabwe participating regularly. We
      hope that this course might serve as a model for other medical schools looking to
      establish courses in this burgeoning field.

PMID- 30185384
TI  - Episode-based cost reduction for endovascular aneurysm repair.
AB  - OBJECTIVE: Effective strategies to reduce costs associated with endovascular
      aneurysm repair (EVAR) remain elusive for many medical centers. In this study,
      targeted interventions to reduce inpatient EVAR costs were identified and
      implemented. METHODS: From June 2015 to February 2016, we analyzed the EVAR
      practice at a high-volume academic medical center to identify, to rank, and
      ultimately to reduce procedure-related costs. In this analysis, per-patient
      direct costs to the hospital were compared before (September 2013-May 2015) and
      after (March 2016-January 2017) interventions were implemented. Improvement
      efforts concentrated on three categories that accounted for a majority of costs:
      implants, rooming costs, and computed tomography scans performed during the index
      hospitalization. RESULTS: Costs were compared between 141 EVAR procedures before
      implementation (PRE period) and 47 EVAR procedures after implementation (POST
      period). Based on data obtained through the Society for Vascular Surgery EVAR
      Cost Demonstration Project, it was determined that implantable device costs were
      higher than those at peer institutions. New purchasing strategies were
      implemented, resulting in a 30.8% decrease in per-case device costs between the
      PRE and POST periods. Care pathways were modified to reduce use of and costs for
      computed tomography scans obtained during the index hospitalization. Compared
      with baseline, per-case imaging costs decreased by 92.9% (P < .001), including a
      99.0% (P = .001) reduction in postprocessing costs. Care pathways were also
      implemented to reduce preprocedural rooming for patients traveling long distances
      the day before surgery, resulting in a 50% decrease in utilization rate (35.4%
      PRE to 17.0% POST; P = .021), without having a significant impact on median
      postprocedural length of stay (PRE, 2 days [interquartile range, 1-11 days];
      POST, 2 days [1-7 days]; P = .185). Medication costs also decreased by 38.2% (P <
      .001) as a hospital-wide effort. CONCLUSIONS: Excessive costs associated with
      EVAR threaten the sustainability of these procedures in health care
      organizations. Targeted cost reduction efforts can effectively reduce expenses
      without compromising quality or limiting patients' access.

PMID- 30185385
TI  - Muscle Architecture Assessment: Strengths, Shortcomings and New Frontiers of in
      Vivo Imaging Techniques.
AB  - Skeletal muscle structural assembly (and its remodeling in response to loading
      unloading states) can be investigated macroscopically by assessing muscle
      architecture, described as fascicle geometric disposition within the muscle. Over
      recent decades, various medical imaging techniques have been developed to
      facilitate the in vivo assessment of muscle architecture. However, the main
      advantages and limitations of these methodologies have been fragmentally
      discussed. In the present article, the main techniques used for the evaluation of
      muscle architecture are presented: conventional B-mode ultrasonography, extended
      field-of-view ultrasound, 3-D ultrasound and magnetic resonance imaging-based
      diffusion tensor imaging. By critically discussing potentials and shortcomings of
      each methodology, we aim to provide readers with an overview of both established
      and new techniques for the in vivo assessment of muscle architecture. This review
      may serve as decision guidance facilitating selection of the appropriate
      technique to be applied in biomedical research or clinical routine.

PMID- 30185381
TI  - Perioperative epidural use and survival outcomes in patients undergoing primary
      debulking surgery for advanced ovarian cancer.
AB  - OBJECTIVE: Epidurals are associated with improved outcomes in some solid tumors,
      presumably due to their effect on surgical stress response. There are limited
      data on the prognostic significance of epidural anesthesia in patients undergoing
      primary debulking surgery (PDS) for advanced ovarian cancer. We sought to assess
      the impact of epidural anesthesia on the survival outcomes of patients undergoing
      PDS for advanced ovarian cancer. METHODS: In this retrospective study,
      consecutive patients with stage IIIB-IV epithelial ovarian, fallopian tube, or
      peritoneal carcinoma who underwent PDS at our institution from 01/2005-12/2013
      were identified. Progression-free survival (PFS) and overall survival (OS) with
      regard to epidural use were analyzed. RESULTS: Of 648 patients, 435 received an
      epidural and 213 did not. Patients in the former group were more likely to have
      higher stage disease (stage IV disease, 26% vs. 16%, respectively; P = .005),
      carcinomatosis (87% vs. 80%, respectively; P = .027), and bulky upper abdominal
      disease (66% vs. 58%, respectively; P = .046). Complete gross resection was
      achieved in 48% and 32%, respectively (P < .001). For the epidural vs. non
      epidural groups, median PFS was 20.8 months and 13.9 months, respectively (P =
      .021); median OS was 62.4 months and 41.9 months, respectively (P < .001). After
      controlling for confounding factors, including residual disease, epidural use was
      independently associated with a decreased risk of progression (HR = 1.327; 95%
      CI, 1.066-1.653) and death (HR = 1.588; 95% CI, 1.224-2.06). CONCLUSIONS:
      Perioperative epidural use was independently associated with improved PFS and OS
      in these patients. Epidural anesthesia at the time of PDS may be warranted in
      this setting.

PMID- 30185386
TI  - Evaluation of Split Renal Function for Children with Kidney Diseases by Renal and
      Vascular Color Ultrasonography.
AB  - Renal dynamic imaging and radionuclide renography use radioactivity to evaluate
      split renal function. We aimed to investigate the use of renal vascular color
      Doppler ultrasonography for evaluation of split renal function in children.
      Thirty-five children with unilateral kidney diseases were enrolled. For patients
      with unilateral renal tumor, peak systolic velocity (Vmax = 113.04 +/- 13.59
      cm/s) and resistance index (RI = 0.73 +/- 0.02) were higher on abnormal compared
      with normal sides (Vmax = 86.03 +/- 6.49 cm/s, RI = 0.62 +/- 0.01), and blood
      perfusion was good, indicating compensatory enhancement in split renal function.
      For unilateral renal cyst, Vmax (58.20 +/- 7.38 cm/s) was lower on the abnormal
      compared with the normal (87.71 +/- 14.83 cm/s) size, and perfusion was poor. For
      unilateral hydronephrosis and renal atrophy, the parameters were similar to those
      of renal cyst, suggesting a weakening of renal function. For unilateral renal
      agenesis, Vmax (106.07 +/- 13.07 cm/s) and RI (0.71 +/- 0.05) were higher, and
      perfusion was good. Renal vascular color Doppler ultrasonography was superior in
      the evaluation of split renal function in children, without being invasive or
      radioactive.

PMID- 30185388
TI  - Amphipathic sulfonamidobenzamides mimicking small antimicrobial marine natural
      products; investigation of antibacterial and anti-biofilm activity against
      antibiotic resistant clinical isolates.
AB  - There is an urgent need for novel antimicrobial agents to address the threat of
      bacterial resistance to modern society. We have used a structural motif found in
      antimicrobial marine hit compounds as a basis for synthesizing a library of
      antimicrobial sulfonamidobenzamide lead compounds. Potent in vitro antimicrobial
      activity against clinically relevant bacterial strains was demonstrated for two
      compounds, G6 and J18, with minimal inhibitory concentrations (MIC) of 4-16
      MUg/ml against clinical methicillin-resistant Staphylococcus aureus (MRSA) and
      vancomycin-resistant Enterococcus faecium (VRE). The two compounds G6 and J18,
      together with several other compounds of this library, also caused >=90%
      eradication of pre-established biofilm of methicillin-resistant S. epidermidis
      (MRSE) at 40 MUg/ml. Using a luciferase assay, the mechanism of action of G6 was
      shown to resemble the biocide chlorhexidine by targeting the bacterial cell
      membrane.

PMID- 30185389
TI  - The Global Health Service Partnership's point-of-care ultrasound initiatives in
      Malawi, Tanzania and Uganda.

PMID- 30185390
TI  - Evaluation of the tensile strength and microbial barrier properties of a novel, 2
      octly-cyanoacrylate based topical skin adhesive.

PMID- 30185391
TI  - Spontaneous pneumothorax as a complication of chronic Jet propulsion fuel-8
      exposure.
AB  - Jet Propulsion Fuel 8 (JP-8) is a kerosene based fuel commonly used in aviation.
      Occupational exposure to JP-8 may lead to negative health outcomes, which were
      described in a small number of studies. We report a case of 33-year-old Caucasian
      male veteran with a history of JP-8 exposure who presented with chronic dyspnea
      and recurrent spontaneous pneumothorax. To our knowledge, this is the first case
      of chronic inhalation injury from JP-8 exposure complicated with recurrent
      secondary spontaneous pneumothorax.

PMID- 30185392
TI  - The Role of Colchicine in Acute Coronary Syndromes.
AB  - PURPOSE: Because inflammation is a key process implicated in the pathogenesis of
      atherosclerosis at all stages, including plaque formation, progression,
      instability, and rupture, and because colchicine has unique anti-inflammatory
      properties, this review article summarizes the pathophysiologic mechanisms
      underpinning inflammation in atherosclerosis and acute coronary syndrome (ACS),
      outlines anti-inflammatory therapeutic approaches that have been tested thus far,
      and evaluates the evidence supporting the potential role of colchicine in
      improving outcomes and reducing cardiovascular morbidity and mortality in
      patients after ACS. METHODS: PubMed was searched for publications on colchicine
      and ACSs and atherosclerosis, and www.clinicaltrials.org was searched for
      completed and ongoing trials of colchicine use in ACSs. FINDINGS: Despite
      contemporary optimal medical therapy, patients remain at a high risk of future
      events after an ACS because of residual inflammation at culprit and nonculprit
      sites. Several attempts have been made to address this with targeted anti
      inflammatory therapies, but until the recent promising results of canakinumab (an
      anti-interleukin-1beta monoclonal antibody), most have failed to find any
      prognostic benefit in large clinical trials with hard end points. The pathogenic
      role of neutrophils and monocytes in atheroinflammation is well established, and
      a fundamental component in this process is the activation of the NOD-like
      receptor protein 3 inflammasome, a cytosolic multiprotein complex that, when
      activated by a stress signal such as cholesterol crystals, drives caspase-1
      dependent release of 2 key proinflammatory cytokines, which are predictive of
      future adverse cardiovascular events: interleukin-1beta and interleukin-18.
      Colchicine is a widely available, inexpensive, and well-tolerated medication
      that, among several anti-inflammatory mechanisms of action, inhibits activation
      of the NOD-like receptor protein 3 inflammasome complex. A seminal trial has
      found the beneficial properties of colchicine in reducing adverse cardiovascular
      events in the stable coronary artery disease population. IMPLICATIONS: Despite
      promising results in small prospective observational and randomized trials, there
      is a need for more evidence evaluating the role of colchicine as a secondary
      preventive agent after ACSs.

PMID- 30185393
TI  - Troublesome News, Fake News, Biased or Incomplete News.

PMID- 30185394
TI  - The Safety and Antiviral Activity of BZF961 with or without Ritonavir in Patients
      Infected with Hepatitis C Virus: A Randomized, Multicenter Trial.
AB  - PURPOSE: Infection with hepatitis C virus is the leading cause of infectious
      disease mortality in the United States. BZF961 is a novel small molecule
      inhibitor of the hepatitis C virus NS3-4A protease. Here we present the results
      of a randomized, double-blinded, placebo-controlled, multicentered study in
      treatment-naive patients with chronic hepatitis C virus genotype-1 infection.
      METHODS: Patients were enrolled sequentially in 2 parts and treated for 3days.
      BZF961 was administered as monotherapy (500mg BID for 3 days) or in combination
      with the cytochrome P450 3A4 inhibitor ritonavir to boost its exposure (BZF961
      10, 20, or 50mg QD or BID). FINDINGS: BZF961 was safe and well tolerated in the
      patients studied with no serious adverse events. There were no appreciable
      differences in adverse events among patients who received BZF961, BZF961 with
      ritonavir, or placebo. There was a significant, clinically meaningful reduction
      in viral load from baseline in patients treated either with BZF961 500mg every
      12hours alone or BZF961 50mg every 12hours in combination with ritonavir.
      Activity against the hepatitis C virus of the lower-dose regimens was apparent
      but more modest. There were no relevant changes from baseline viral loads in
      placebo-treated patients. IMPLICATIONS: Coadministration of ritonavir with BZF961
      boosted BZF961 exposure (including Cmin, which is the clinically relevant
      parameter associated with antiviral activity) in a therapeutic range with less
      variability compared with BZF961 alone. For strategic reasons, BZF961 is no
      longer under development.

PMID- 30185395
TI  - Pharmacokinetics, Safety, and Tolerability of the Direct-acting Hepatitis C
      Antiviral Sofosbuvir in HealthyChineseSubjects.
AB  - PURPOSE: The purpose of this study was to investigate the safety, tolerability,
      and pharmacokinetic profile of sofosbuvir and its metabolites after a single dose
      of sofosbuvir 400mg and once daily dosing of sofosbuvir 400mg for 7days in
      healthy Chinese subjects. METHODS: This Phase I, open-label, single- and multiple
      dose study enrolled 14 Chinese subjects aged 18 to 45years with an approximately
      even distribution of healthy male (n = 9) and nonpregnant, nonlactating female
      subjects (n = 5). Subjects received a single oral dose of sofosbuvir 400mg (one
      tablet) (morning, fasted conditions; single-dose treatment). After a 3-day
      washout, subjects received oral sofosbuvir 400mg (one tablet) (morning, fasted)
      for 7days (multiple dose treatment). FINDINGS: No significant accumulation of
      sofosbuvir, GS-566500, or GS-331007 was observed. Steady state of the major
      metabolite GS-331007 was achieved after 4days of consecutive dosing with
      sofosbuvir 400mg once daily. Sofosbuvir was generally well tolerated.
      IMPLICATIONS: Overall, this study supports the further evaluation of sofosbuvir
      400mg in the Chinese population. The pharmacokinetic properties of sofosbuvir, GS
      556500, and GS-311007 were found to be broadly similar in healthy Chinese
      subjects compared with non-Chinese subjects in previous sofosbuvir studies.
      ChinaDrugTrials.org.cn identifier: CTR20150249.

PMID- 30185396
TI  - Oral Dipyridamole-Associated Circulatory Collapse.
AB  - Extended-release dipyridamole plus aspirin is widely used for secondary
      prevention of ischemic stroke, although the molecular pharmacodynamics of
      dipyridamole are not completely determined. Adverse effects of fixed-dose
      combination of aspirin and dipyridamole include headache, bleeding, and
      gastrointestinal events. Previously, intravenous infusion of dipyridamole in
      cardiac stress testing has been associated with cardiogenic shock and pulmonary
      edema. Herein, we report a case study of a 72-year-old man, presented with a
      transient ischemic attack who suffered a circulatory collapse after an oral dose
      of 200 mg extended-release dipyridamole. The possible molecular mechanisms of
      dipyridamole on the cardiovascular system are reviewed. This is the first case
      report of a circulatory collapse induced by an oral intake of dipyridamole.

PMID- 30185397
TI  - Doppler Resistivity and Cerebral Small Vessel Disease: Hemodynamic Structural
      Correlation and Usefulness for the Etiological Classification of Acute Ischemic
      Stroke.
AB  - INTRODUCTION AND GOAL: Lacunar stroke is defined as an <1.5 cm diameter infarct
      located in the territory of a perforating artery, that is not accessible for
      direct study using conventional imaging techniques. Diagnosis requires exclusion
      of other causes. It usually occurs in the context of chronic cerebral small
      vessel disease, which can be suspected during the neurosonography study in the
      form of high pulsatility [PI] or resistance index [RI]. Clinical research was
      performed to confirm that PI and RI correlate with cerebral small vessel lesion
      burden and to determine whether these parameters are useful for supporting a
      lacunar origin (LO) in acute stroke. MATERIAL AND METHODS: We prospectively
      recorded internal carotid artery resistivity and the Fazekas score for all
      patients with acute ischemic stroke who met inclusion but not exclusion criteria
      over a 6-month period. RESULTS: The study population comprised 74 patients. A
      correlation was observed between the Fazekas score and resistivity. Both
      parameters predicted a LO, with an area under the curve of .78 and .696,
      respectively. The optimal cut-offs were PI = .96/RI = .58 for screening
      (sensitivity, 96%) and PI = 1.46/RI = .83 for confirmation (specificity, 89%).
      CONCLUSIONS: Doppler ultrasound is a useful technique for determining the LO of
      acute stroke.

PMID- 30185398
TI  - Closure versus Medical Therapy for Patent Foramen Ovale in Patients with
      Cryptogenic Stroke: An Updated Meta-Analysis of Randomized Controlled Trials.
AB  - BACKGROUND: Debate continues about whether percutaneous closure of patent foramen
      ovale (PFO) is a better strategy for the treatment of patients with cryptogenic
      stroke in comparison with medical therapy alone. We performed an updated meta
      analysis of 6 randomized controlled trials (RCTs) to assess the effectiveness and
      safety of percutaneous closure of PFO as secondary prevention for patients with
      previous cryptogenic stroke compared to medical therapy. MATERIALS AND METHODS:
      MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, conference
      proceedings, and Internet-based resources were retrieved in March 2018 for
      eligible RCTs. The primary effectiveness outcome was recurrent strokes. RESULTS:
      Six studies meeting our selection criteria were identified. Among 3560
      participants, 1889 patients were assigned to PFO closure and 1671 patients to
      medical therapy. There were no significant differences among the baseline
      characteristics. The pooled incidence of recurrent strokes was 1.96% in the PFO
      closure group and 4.60% in the medical therapy group (Relative risk [RR] .39, 95%
      confidence interval [CI] .18-.82, P = .01). Newly detected atrial fibrillation
      occurred in 77 of 1844 (4.18%) patients in the PFO closure group and in 12 of
      1667 (.72%) patients in the medical therapy group (RR 4.56, 95% CI 2.21-9.41, P
      <.0001). There was no difference in terms of serious adverse events, total
      mortality or bleeding between 2 groups. CONCLUSIONS: Our updated meta-analysis
      suggests that in patients with PFO and cryptogenic stroke, the rate of recurrent
      stroke is significantly reduced with percutaneous closure of PFO compared to the
      medical therapy.

PMID- 30185399
TI  - One-Quarter of People Leave Inpatient Stroke Rehabilitation with Physical
      Capacity for Community Ambulation.
AB  - BACKGROUND AND PURPOSE: Ability to walk in the community is important for
      independence and participation in life roles, but is difficult for many people
      following stroke. The purpose of this study was to determine the proportion of
      people with stroke with the physical capacity to be independent community
      ambulators at discharge from a publicly funded inpatient rehabilitation setting.
      METHOD: Consecutive medical records were audited to collate walking outcome at
      discharge, and to clarify if people with stroke had potential to walk
      independently in the community as defined by 4 criteria: independence with
      stairs; ability to traverse slopes and inclines; walking speed of .8m/s or more;
      and walking distance 367 m or higher on 6-Minute Walk Test. RESULTS: While 80% of
      the 124 persons with stroke could walk indoors, only 27% could perform 4
      essential skills needed to walk independently in the community at discharge from
      hospital. The proportion that met each criterion was 52% for stairs, 39% for
      slopes and inclines, 58% for speed, and 40% for distance. For the overall sample,
      mean (standard deviation) walking speed was .90 (.33) m/s, and distance for 6
      Minute Walk Test was 349.6 (146.5) m. DISCUSSION AND CONCLUSION: A retrospective
      review found that three quarters of stroke survivors lacked physical capacity for
      4 skills required to walk independently in the community at the time of discharge
      from a public inpatient rehabilitation. Our findings recommend that people with
      stroke have access to outpatient physical rehabilitation to optimize walking
      outcome.

PMID- 30185401
TI  - Different presentations of patients with transcobalamin II deficiency: A single
      center experience from Turkey.
AB  - OBJECTIVE: Transcobalamin II (TC) deficiency is a rare autosomal recessive
      disease characterized by decreased cobalamin availability, which in turn causes
      accumulation of homocysteine and methylmalonic acid. The presenting clinical
      features are failure to thrive, diarrhea, megaloblastic anemia, pancytopenia,
      neurologic abnormalities and also recurrent infections due to immune
      abnormalities in early infancy. MATERIALS AND METHODS: Here, we report the
      clinical and laboratory features of six children with TC deficiency who are all
      molecularly confirmed. RESULTS: The patients were admitted between 1 and 7 months
      of age with anemia or pancytopenia. Unexpectedly, one patient had a serum vitamin
      B12 level lower than normal range and the other one had not significantly
      elevated serum homocysteine levels. Three patients had lymphopenia, four had
      neutropenia and two had also hypogammaglobulinemia suggesting the consideration
      of TC deficiency in the differential diagnosis of immune deficiency.
      Hemophagocytic lymphohistiocytosis was also detected in one patient. Furthermore,
      two patients had vacuolization in the myeloid lineage in bone marrow aspiration,
      which may be an additional finding of TC deficieny. The hematological
      abnormalities in all patients resolved after parenteral cobalamin treatment. In
      the follow-up, two patients showed neurological impairment such as impaired
      speech and walking. Among our six cases who were all molecularly confirmed, two
      had the mutation which was reported in the TC deficient patients of Turkish
      ancestry. Also, a novel TCN2 gene mutation was detected in one of the remaining
      cases. CONCLUSION: TC deficieny should be considered in differential diagnosis of
      infants with immunological abnormalities as well as cytopenia and neurological
      dysfunction. Early recognition of this rare condition and initiation of adequate
      treatment is critical for the disease control and better prognosis.

PMID- 30185400
TI  - CAR-T Cell Therapy: A Door Is Open to Find Innumerable Possibilities of
      Treatments for Cancer Patients
AB  - Seven years ago a chronic lymphocytic leukemia patient was for the first time
      successfully treated with chimeric antigen receptor (CAR)-modified T cells (CAR-T
      cells) to target CD19 overexpression in tumor cells. This was the beginning of
      the development of a new type of immunotherapy treatment in cancer patients.
      Since then, identification of novel antigens expressed in tumor cells and
      optimization of both CAR constructs and protocols of administration have opened
      up new avenues for the successful treatment of other hematological malignancies.
      However, research still continues to avoid some problems such as toxicities
      associated with the treatment and to find strategies to avoid tumor cell immune
      evasion mechanisms. On the other hand, for solid tumors, CAR-T therapy results
      are still in an early phase. In contrast to hematological malignancies, the
      complex tumor heterogeneity of solid tumors has led to the research of novel and
      challenging strategies to improve CAR-T cell activity. Here, we will review the
      main clinical results obtained with CAR-T cells in hematological malignancies,
      specifically focusing on CAR-T-19 and CAR-T against B-cell maturation antigen
      (CAR-T-BCMA). Moreover, we will mention the main problems that decrease CAR-T
      cell activity in solid tumors and the strategies to overcome them. Finally, we
      will present some of the first clinical results obtained for solid tumors.

PMID- 30185402
TI  - Digital Technology for Caregivers of People With Psychosis: Systematic Review.
AB  - BACKGROUND: Psychotic disorders are severe mental health conditions that
      adversely affect the quality of life and life expectancy. Schizophrenia, the most
      common and severe form of psychosis affects 21 million people globally. Informal
      caregivers (families) are known to play an important role in facilitating patient
      recovery outcomes, although their own health and well-being could be adversely
      affected by the illness. The application of novel digital interventions in mental
      health care for patient groups is rapidly expanding; interestingly, however, far
      less is known about their role with family caregivers. OBJECTIVE: This study
      aimed to systematically identify the application of digital interventions that
      focus on informal caregivers of people with psychosis and describe their
      outcomes. METHODS: We completed a search for relevant papers in four electronic
      databases (EMBASE, MEDLINE, PsycINFO, and Web of Science). The search also
      included the Cochrane database and manual search of reference lists of relevant
      papers. The search was undertaken in accordance with Preferred Reporting Items
      for Systematic Reviews and Meta-Analyses reporting guidelines. RESULTS: The
      search identified 9 studies derived from 8 unique datasets. Most studies were
      assessments of feasibility and were undertaken in the United States.
      Interventions were predominately Web-based, with a focus on improving the
      caregivers' knowledge and understanding about psychosis. CONCLUSIONS: This study
      offers preliminary support for the feasibility and acceptability of digital
      interventions for psychosis in informal caregiver populations. However, the
      findings underpin a clear need for greater development in the range of caregiver
      focused digital approaches on offer and robust evaluation of their outcomes. The
      use of digital approaches with caregiver populations seemingly lags someway
      behind the significant developments observed in patient groups.

PMID- 30185403
TI  - Visual Cancer Communication on Social Media: An Examination of Content and
      Effects of #Melanomasucks.
AB  - BACKGROUND: Instagram is increasingly becoming a platform on which visual
      communication of cancer takes place, but few studies have investigated the
      content and effects. In particular, a paucity of research has evaluated the
      effects of visual communication of cancer on participative engagement outcomes.
      OBJECTIVE: The objective of our study was to investigate cancer-related beliefs
      and emotions shared on Instagram and to examine their effects on participative
      engagement outcomes including likes, comments, and social support. METHODS: This
      study analyzed the content of 441 posts of #melanomasucks on Instagram and
      assessed the effects of the content characteristics on outcomes, including the
      number of likes and comments and types of social support using group least
      absolute shrinkage and selection operator logistic regression. RESULTS: Posts
      about controlling melanoma were most frequent (271/441, 61.5%), followed by 240
      (54.4%) posts about outcomes of having melanoma. Ninety posts (20.4%) were about
      the causes of melanoma. A greater number of posts expressed positive (159/441,
      36.1%) than negative emotions (100/441, 22.7%). Eighty posts (18.1%) expressed
      hope, making it the most frequently expressed emotion; 49 posts expressed fear
      (11.1%), 46 were humorous (10.4%), and 46 showed sadness (10.4%). Posts about
      self behavior as a cause of melanoma decreased likes (P<.001) and social support
      comments (P=.048). Posts about physical consequences of melanoma decreased likes
      (P=.02) but increased comments (P<.001) and emotional social support (P<.001);
      posts about melanoma treatment experience increased comments (P=.03) and
      emotional social support (P<.001). None of the expressions of positive emotions
      increased likes, comments, or social support. Expression of anger increased the
      number of likes (P<.001) but those about fear (P<.001) and joy (P=.006) decreased
      the number of likes. Posts about fear (P=.003) and sadness (P=.003) increased
      emotional social support. Posts showing images of melanoma or its treatment on
      the face or body parts made up 21.8% (96/441) of total posts. Inclusion of images
      increased the number of comments (P=.001). CONCLUSIONS: To our knowledge, this is
      the first investigation of the content and effects of user-generated visual
      cancer communication on social media. The findings show where the self-expressive
      and social engagement functions of #melanomasucks converge and diverge, providing
      implications for extending research on the commonsense model of illness and for
      developing conceptual frameworks explaining participative engagement on social
      media.

PMID- 30185404
TI  - Prevention of HIV and Other Sexually Transmissible Infections in Expatriates and
      Traveler Networks: Qualitative Study of Peer Interaction in an Online Forum.
AB  - BACKGROUND: In high-income countries such as Australia, an increasing proportion
      of HIV cases have been acquired overseas, including among expatriates and
      travelers. Australia's national strategies have highlighted the need for public
      health interventions for priority populations. One approach is to expand efforts
      to places or spaces where expatriate communities reside. Online settings such as
      forums used by expatriates and travelers have potential for preventing sexually
      transmissible infections with those hard to reach through more traditional
      interventions. OBJECTIVE: Our objectives were to (1) identify and describe
      domains of social interaction and engagement in 1 online forum used by Australian
      expatriates and travelers living or working in Thailand; and (2) make
      recommendations to health-promoting organizations and policy makers regarding the
      role of these forums in public health interventions with mobile populations who
      may be at risk of acquiring HIV or other sexually transmissible infections.
      METHODS: We identified forums and users in 2 stages. We identified 13 online
      forums and analyzed them for inclusion criteria. We searched 1 forum that met the
      required criteria for users who met inclusion criteria (n=5). Discussion threads,
      rather than individual posts, were units of analysis. For each user, we collected
      as transcripts the first 100 posts and 10 most recent posts, including the thread
      in which they were posted. We analyzed and thematically coded each post (n=550).
      Transcripts and analyses were reviewed and refined by multiple members of the
      research team to improve rigor. Themes were not totally emergent but explored
      against symbolic interactionism concepts of presentation of self, meaning, and
      socialization. RESULTS: Key domains were as follows: the forum (characteristics
      of the space and reasons for use), gaining access (forum hierarchy and rules),
      identity (presentation of self and role of language), advice, support, and
      information (sources of information, support provided, influencers, topics of
      discussion, and receptiveness to advice), and risk (expectations and
      perceptions). The forum exhibited evidence of unique language, rules and norms,
      and processes for managing conflict and key influencers. The forum was a
      substantial source of health information and advice provided to users via
      confirmation, reassurance, or affirmation of beliefs and experiences. Risk
      perception and expectations varied. Risk taking, including around sex, appeared
      to be a key expectation of travel or the experience of being an expatriate or
      traveler. CONCLUSIONS: Australian expatriate and long-term traveler participation
      in the online forum formed, influenced, and reinforced knowledge, attitudes,
      interaction, and identity. Such forums can be used by policy makers and health
      promoting organizations to provide supplementary sources of support and
      information to hard-to-reach mobile populations who may be at risk of acquiring
      HIV or other sexually transmissible infections. This will complement existing
      engagement with health professionals and other public health interventions.

PMID- 30185405
TI  - Patient Experiences of Web-Based Cognitive Behavioral Therapy for Heart Failure
      and Depression: Qualitative Study.
AB  - BACKGROUND: Web-based cognitive behavioral therapy (wCBT) has been proposed as a
      possible treatment for patients with heart failure and depressive symptoms.
      Depressive symptoms are common in patients with heart failure and such symptoms
      are known to significantly worsen their health. Although there are promising
      results on the effect of wCBT, there is a knowledge gap regarding how persons
      with chronic heart failure and depressive symptoms experience wCBT. OBJECTIVE:
      The aim of this study was to explore and describe the experiences of
      participating and receiving health care through a wCBT intervention among persons
      with heart failure and depressive symptoms. METHODS: In this qualitative,
      inductive, exploratory, and descriptive study, participants with experiences of a
      wCBT program were interviewed. The participants were included through purposeful
      sampling among participants previously included in a quantitative study on wCBT.
      Overall, 13 participants consented to take part in this study and were
      interviewed via telephone using an interview guide. Verbatim transcripts from the
      interviews were qualitatively analyzed following the recommendations discussed by
      Patton in Qualitative Research & Evaluation Methods: Integrating Theory and
      Practice. After coding each interview, codes were formed into categories.
      RESULTS: Overall, six categories were identified during the analysis process.
      They were as follows: "Something other than usual health care," "Relevance and
      recognition," "Flexible, understandable, and safe," "Technical problems,"
      "Improvements by real-time contact," and "Managing my life better." One central
      and common pattern in the findings was that participants experienced the wCBT
      program as something they did themselves and many participants described the
      program as a form of self-care. CONCLUSIONS: Persons with heart failure and
      depressive symptoms described wCBT as challenging. This was due to participants
      balancing the urge for real-time contact with perceived anonymity and not
      postponing the work with the program. wCBT appears to be a valuable tool for
      managing depressive symptoms.

PMID- 30185406
TI  - Medical-Grade Physical Activity Monitoring for Measuring Step Count and Moderate
      to-Vigorous Physical Activity: Validity and Reliability Study.
AB  - BACKGROUND: The use of physical activity (PA) monitors is commonly associated
      with an increase in habitual PA level in healthy and clinical populations. The
      PiezoRx is a medical-grade PA monitor that uses adjustable step rate thresholds
      to estimate moderate-to-vigorous physical activity (MVPA) and is a valid
      indicator of free-living PA in adults. Laboratory validation of step count
      derived MVPA in adults is needed to justify the use of these monitors in clinical
      practice to track individuals' progress toward meeting PA guidelines that are
      based on MVPA, not steps. OBJECTIVE: The objective of our study was to assess the
      validity and interinstrument reliability of the PiezoRx to derive step count and
      MVPA in a laboratory setting compared with criterion measures and other
      frequently used PA monitors in a diverse sample of adults. METHODS: The adult
      participants (n=43; 39.4 years, SD 15.2) wore an Omron HJ-320 pedometer, an
      ActiGraph GT3X accelerometer, and four PiezoRx monitors during a progressive
      treadmill protocol conducted for 6 minutes at speeds of 2.4, 3.2, 4.0, 5.6, 6.4,
      and 7.2 km/hour, respectively. The four PiezoRx monitors were set at different
      MVPA step rate thresholds (MPA in steps/minute/VPA in steps/minute) 100/120,
      110/130, height adjusted, and height+fitness adjusted. RESULTS: The PiezoRx was
      more correlated (intraclass correlation, ICC=.97; P<.001) to manual step counting
      than the ActiGraph (ICC=.72; P<.001) and Omron (ICC=.62; P<.001). The PiezoRxs
      absolute percent error in measuring steps was 2.2% (ActiGraph=15.9%;
      Omron=15.0%). Compared with indirect calorimetry, the height-adjusted PiezoRx and
      ActiGraph were accurate measures of the time spent in MVPA (both ICC=.76;
      P<.001). CONCLUSIONS: The PiezoRx PA monitor appears to be a valid and reliable
      measure of step count and MVPA in this diverse sample of adults. The device's
      ability to measure MVPA may be improved when anthropometric differences are
      considered, performing at par or better than a research grade accelerometer.

PMID- 30185407
TI  - Effect of Peripheral Defocus on Axial Eye Growth and Modulation of Refractive
      Error in Hyperopes: Protocol for a Nonrandomized Clinical Trial.
AB  - BACKGROUND: Hyperopia occurs due to insufficient ocular growth and a failure to
      emmetropize in childhood. In anisohyperopia, it is unclear why one eye may remain
      hyperopic while the fellow eye grows toward an emmetropic state. Animal studies
      have shown that manipulating peripheral defocus through optical means while
      simultaneously providing correct axial focus can either discourage or encourage
      axial eye growth to effectively treat myopia or hyperopia, respectively. Myopia
      progression and axial eye growth can be significantly reduced in children and
      adolescents through the use of multifocal contact lenses. These contact lenses
      correct distance central myopia while simultaneously imposing relative peripheral
      myopic defocus. The effect of correcting distance central hyperopia while
      simultaneously imposing relative peripheral hyperopic defocus is yet to be
      elucidated in humans. OBJECTIVE: The objective of our study is to understand the
      natural progression of axial eye growth and refractive error in hyperopes and
      anisohyperopes and to establish whether axial eye growth and refractive error can
      be modified using multifocal contact lenses in hyperopes and anisohyperopes.
      METHODS: There are 3 elements to the program of research. First, the natural
      progression of axial eye growth and refractive error will be measured in
      spectacle-wearing hyperopic and anisohyperopic subjects aged between 5 and <20
      years. In other words, the natural growth of the eye will be followed without any
      intervention. Second, as a paired-eye control study, anisohyperopes aged between
      8 and <16 years will be fitted with a center-near multifocal design contact lens
      in their more hyperopic eye and a single-vision contact lens in the fellow eye if
      required. The progression of axial eye growth and refractive error will be
      measured and compared. Third, subjects aged between 8 and <16 years with similar
      levels of hyperopia in each eye will be fitted with center-near multifocal design
      contact lenses in each eye; the progression of axial eye growth and refractive
      error in these subjects will be measured and compared with those of subjects in
      the natural progression study. RESULTS: Recruitment commenced on 6 June 2016 and
      was completed on 8 April 2017. We estimate the data collection to be completed by
      April 2020. CONCLUSIONS: This trial will establish whether axial eye growth can
      be accelerated in children with hyperopia by imposing relative peripheral
      hyperopic defocus using center-near multifocal contact lenses. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT02686879;
      https://clinicaltrials.gov/ct2/show/NCT02686879 (Archived by Webcite at
      http://www.webcitation.org/71o5p3fD2). REGISTERED REPORT IDENTIFIER: RR1
      10.2196/9320.

PMID- 30185409
TI  - A novel role for Lyl1 in primitive erythropoiesis.
AB  - Stem cell leukemia (Scl or Tal1) and lymphoblastic leukemia 1 (Lyl1) encode
      highly related members of the basic helix-loop-helix family of transcription
      factors that are co-expressed in the erythroid lineage. Previous studies have
      suggested that Scl is essential for primitive erythropoiesis. However, analysis
      of single-cell RNA-seq data of early embryos showed that primitive erythroid
      cells express both Scl and Lyl1 Therefore, to determine whether Lyl1 can function
      in primitive erythropoiesis, we crossed conditional Scl knockout mice with mice
      expressing a Cre recombinase under the control of the Epo receptor, active in
      erythroid progenitors. Embryos with 20% expression of Scl from E9.5 survived to
      adulthood. However, mice with reduced expression of Scl and absence of Lyl1
      (double knockout; DKO) died at E10.5 because of progressive loss of
      erythropoiesis. Gene expression profiling of DKO yolk sacs revealed loss of Gata1
      and many of the known target genes of the SCL-GATA1 complex. ChIP-seq analyses in
      a human erythroleukemia cell line showed that LYL1 exclusively bound a small
      subset of SCL targets including GATA1. Together, these data show for the first
      time that Lyl1 can maintain primitive erythropoiesis.

PMID- 30185408
TI  - Pool size estimations for dense-core vesicles in mammalian CNS neurons.
AB  - Neuropeptides are essential signaling molecules transported and secreted by dense
      core vesicles (DCVs), but the number of DCVs available for secretion, their
      subcellular distribution, and release probability are unknown. Here, we
      quantified DCV pool sizes in three types of mammalian CNS neurons in vitro and in
      vivo Super-resolution and electron microscopy reveal a total pool of 1,400-18,000
      DCVs, correlating with neurite length. Excitatory hippocampal and inhibitory
      striatal neurons in vitro have a similar DCV density, and thalamo-cortical axons
      in vivo have a slightly higher density. Synapses contain on average two to three
      DCVs, at the periphery of synaptic vesicle clusters. DCVs distribute equally in
      axons and dendrites, but the vast majority (80%) of DCV fusion events occur at
      axons. The release probability of DCVs is 1-6%, depending on the stimulation.
      Thus, mammalian CNS neurons contain a large pool of DCVs of which only a small
      fraction can fuse, preferentially at axons.

PMID- 30185411
TI  - 'Rooming-in' could be an effective non-pharmacological treatment for infants with
      neonatal abstinence syndrome.

PMID- 30185412
TI  - Pain.
AB  - EBN Perspectives brings together key issues from the commentaries in one of our
      nursing topic themes. 

PMID- 30185410
TI  - Targeted DamID reveals differential binding of mammalian pluripotency factors.
AB  - The precise control of gene expression by transcription factor networks is
      crucial to organismal development. The predominant approach for mapping
      transcription factor-chromatin interactions has been chromatin
      immunoprecipitation (ChIP). However, ChIP requires a large number of homogeneous
      cells and antisera with high specificity. A second approach, DamID, has the
      drawback that high levels of Dam methylase are toxic. Here, we modify our
      targeted DamID approach (TaDa) to enable cell type-specific expression in
      mammalian systems, generating an inducible system (mammalian TaDa or MaTaDa) to
      identify genome-wide protein/DNA interactions in 100 to 1000 times fewer cells
      than ChIP-based approaches. We mapped the binding sites of two key pluripotency
      factors, OCT4 and PRDM14, in mouse embryonic stem cells, epiblast-like cells and
      primordial germ cell-like cells (PGCLCs). PGCLCs are an important system for
      elucidating primordial germ cell development in mice. We monitored PRDM14 binding
      during the specification of PGCLCs, identifying direct targets of PRDM14 that are
      key to understanding its crucial role in PGCLC development. We show that MaTaDa
      is a sensitive and accurate method for assessing cell type-specific transcription
      factor binding in limited numbers of cells.

PMID- 30185413
TI  - Revised 2017 international consensus on ANCA testing in small vessel vasculitis:
      support from an external quality assessment.

PMID- 30185414
TI  - Chronic hydroxychloroquine/chloroquine exposure for connective tissue diseases
      and risk of Alzheimer's disease: a population-based cohort study.

PMID- 30185416
TI  - Response to: 'The revised 2017 international consensus on ANCA testing in small
      vessel vasculitis: support from an external quality assessment' by Broeders et
      al.

PMID- 30185415
TI  - Pre-existing antiacetylcholine receptor autoantibodies and B cell lymphopaenia
      are associated with the development of myositis in patients with thymoma treated
      with avelumab, an immune checkpoint inhibitor targeting programmed death-ligand
      1.

PMID- 30185418
TI  - Ethnic pay gap among NHS doctors.

PMID- 30185417
TI  - Galectin-9 is an easy to measure biomarker for the interferon signature in
      systemic lupus erythematosus and antiphospholipid syndrome.
AB  - OBJECTIVE: The interferon (IFN) signature is related to disease activity and
      vascular disease in systemic lupus erythematosus (SLE) and antiphospholipid
      syndrome (APS) and represents a promising therapeutic target. Quantification of
      the IFN signature is currently performed by gene expression analysis, limiting
      its current applicability in clinical practice. Therefore, the objective of this
      study was to establish an easy to measure biomarker for the IFN signature.
      METHODS: Serum levels of galectin-9, CXCL-10 (IP-10) and tumour necrosis factor
      receptor type II (TNF-RII) were measured in patients with SLE, SLE+APS and
      primary APS (PAPS) and healthy controls (n=148) after an initial screening of
      serum analytes in a smaller cohort (n=43). Analytes were correlated to measures
      of disease activity and the IFN signature. The performance of galectin-9, CXCL-10
      and TNF-RII as biomarkers to detect the IFN signature was assessed by receiver
      operating characteristic curves. RESULTS: Galectin-9, CXCL-10 and TNF-RII were
      elevated in patients with SLE, SLE+APS and PAPS (p<0.05) and correlated with
      disease activity and tissue factor expression. Galectin-9 correlated stronger
      than CXCL-10 or TNF-RII with the IFN score (r=0.70, p<0.001) and was superior to
      CXCL-10 or TNF-RII in detecting the IFN signature (area under the curve (AUC)
      0.86). Importantly, in patients with SLE(+/-APS), galectin-9 was also superior to
      anti-dsDNA antibody (AUC 0.70), or complement C3 (AUC 0.70) and C4 (AUC 0.78)
      levels in detecting the IFN signature. CONCLUSION: Galectin-9 is a novel, easy to
      measure hence clinically applicable biomarker to detect the IFN signature in
      patients with systemic autoimmune diseases such as SLE and APS.

PMID- 30185419
TI  - Smad7 Promotes Healing of Radiotherapy-Induced Oral Mucositis without
      Compromising Oral Cancer Therapy in a Xenograft Mouse Model.
AB  - Purpose: We previously reported preventive and therapeutic effects of Smad7, a
      multifunctional protein, on radiotherapy (RT)-induced mucositis in mice without
      promoting human oral cancer cell survival or migration in vitro The current study
      aims to determine whether a Smad7-based biologic can treat existing oral
      mucositis during radiotherapy for oral cancer and whether this treatment
      compromises RT-induced cancer cell killing in neighboring oral
      cancer.Experimental Design: We transplanted human oral cancer cells into the
      tongues of mice and applied craniofacial irradiation to simultaneously kill tumor
      cells and induce oral mucositis, thus modeling RT and mucositis in oral cancer
      patients. We topically applied a recombinant human Smad7 protein fused with the
      cell-penetrating Tat tag (Tat-Smad7) to the oral mucosa of tumor-bearing mice
      post RT when oral mucositis began to develop.Results: Topically applied Tat-Smad7
      penetrated cells in both the oral mucosa and oral cancer, attenuating TGFbeta and
      NF-kappaB signaling as well as inflammation at both sites. Tat-Smad7 treatment
      alleviated oral mucositis with reductions in DNA damage and apoptosis in
      keratinocytes, but increased keratinocyte proliferation compared with vehicle
      treated mucositis lesions. In contrast, adjacent oral cancer exposed to Tat-Smad7
      did not show alterations in proliferation or direct DNA damage, but showed
      increased oxidative stress damage and apoptosis compared with tumors treated with
      vehicle.Conclusions: Our results suggest that short-course Tat-Smad7 application
      to oral mucositis promotes its healing but does not compromise the cytotoxic
      effect of RT on oral cancer and has context-specific effects on oral mucosa
      versus oral cancer. Clin Cancer Res; 1-11. (c)2018 AACR.

PMID- 30185420
TI  - Lobular Carcinomas In Situ Display Intralesion Genetic Heterogeneity and Clonal
      Evolution in the Progression to Invasive Lobular Carcinoma.
AB  - Purpose: Lobular carcinoma in situ (LCIS) is a preinvasive lesion of the breast.
      We sought to define its genomic landscape, whether intralesion genetic
      heterogeneity is present in LCIS, and the clonal relatedness between LCIS and
      invasive breast cancers.Experimental Design: We reanalyzed whole-exome sequencing
      (WES) data and performed a targeted amplicon sequencing validation of mutations
      identified in 43 LCIS and 27 synchronous more clinically advanced lesions from 24
      patients [9 ductal carcinomas in situ (DCIS), 13 invasive lobular carcinomas
      (ILC), and 5 invasive ductal carcinomas (IDC)]. Somatic genetic alterations,
      mutational signatures, clonal composition, and phylogenetic trees were defined
      using validated computational methods.Results: WES of 43 LCIS lesions revealed a
      genomic profile similar to that previously reported for ILCs, with CDH1 mutations
      present in 81% of the lesions. Forty-two percent (18/43) of LCIS were found to be
      clonally related to synchronous DCIS and/or ILCs, with clonal evolutionary
      patterns indicative of clonal selection and/or parallel/branched progression.
      Intralesion genetic heterogeneity was higher among LCIS clonally related to
      DCIS/ILC than in those nonclonally related to DCIS/ILC. A shift from aging to
      APOBEC-related mutational processes was observed in the progression from LCIS to
      DCIS and/or ILC in a subset of cases.Conclusions: Our findings support the
      contention that LCIS has a repertoire of somatic genetic alterations similar to
      that of ILCs, and likely constitutes a nonobligate precursor of breast cancer.
      Intralesion genetic heterogeneity is observed in LCIS and should be considered in
      studies aiming to develop biomarkers of progression from LCIS to more advanced
      lesions. Clin Cancer Res; 1-13. (c)2018 AACR.

PMID- 30185421
TI  - A Noninvasive Blood-based Combinatorial Proteomic Biomarker Assay to Detect
      Breast Cancer in Women over age 50 with BI-RADS 3, 4, or 5 Assessment.
AB  - Purpose: With improvements in breast cancer imaging, there has been a
      corresponding increase in false-positives and avoidable biopsies. There is a need
      to better differentiate when a breast biopsy is warranted and determine
      appropriate follow-up. This study describes the design and clinical performance
      of a combinatorial proteomic biomarker assay (CPBA), Videssa Breast, in women
      over age 50 years.Experimental Design: A BI-RADS 3, 4, or 5 assessment was
      required for clinical trial enrollment. Serum was collected prior to breast
      biopsy and subjects were followed for 6-12 months and clinically relevant
      outcomes were recorded. Samples were split into training (70%) and validation
      (30%) cohorts with an approximate 1:4 case:control ratio in both arms.Results: A
      CPBA that combines biomarker data with patient clinical data was developed using
      a training cohort (469 women, cancer incidence: 18.5%), resulting in 94%
      sensitivity and 97% negative predictive value (NPV). Independent validation of
      the final algorithm in 194 subjects (breast cancer incidence: 19.6%) demonstrated
      a sensitivity of 95% and a NPV of 97%. When combined with previously published
      data for women under age 50, Videssa Breast achieves a comprehensive 93%
      sensitivity and 98% NPV in a population of women ages 25-75. Had Videssa Breast
      results been incorporated into the clinical workflow, approximately 45% of
      biopsies might have been avoided.Conclusions: Videssa Breast combines serum
      biomarkers with clinical patient characteristics to provide clinicians with
      additional information for patients with indeterminate breast imaging results,
      potentially reducing false-positive breast biopsies. Clin Cancer Res; 1-8.
      (c)2018 AACR.

PMID- 30185422
TI  - Strategy for Tumor-Selective Disruption of Androgen Receptor Function in the
      Spectrum of Prostate Cancer.
AB  - Purpose: Testosterone suppression in prostate cancer is limited by serious side
      effects and resistance via restoration of androgen receptor (AR) functionality.
      ELK1 is required for AR-dependent growth in various hormone-dependent and
      castration-resistant prostate cancer models. The amino-terminal domain of AR
      docks at two sites on ELK1 to coactivate essential growth genes. This study
      explores the ability of small molecules to disrupt the ELK1-AR interaction in the
      spectrum of prostate cancer, inhibiting AR activity in a manner that would
      predict functional tumor selectivity.Experimental Design: Small-molecule drug
      discovery and extensive biological characterization of a lead compound.Results:
      We have discovered a lead molecule (KCI807) that selectively disrupts ELK1
      dependent promoter activation by wild-type and variant ARs without interfering
      with ELK1 activation by ERK. KCI807 has an obligatory flavone scaffold and
      functional hydroxyl groups on C5 and C3'. KCI807 binds to AR, blocking ELK1
      binding, and selectively blocks recruitment of AR to chromatin by ELK1. KCI807
      primarily affects a subset of AR target growth genes selectively suppressing AR
      dependent growth of prostate cancer cell lines with a better inhibitory profile
      than enzalutamide. KCI807 also inhibits in vivo growth of castration/enzalutamide
      resistant cell line-derived and patient-derived tumor xenografts. In the rodent
      model, KCI807 has a plasma half-life of 6 hours, and maintenance of its antitumor
      effect is limited by self-induced metabolism at its 3'-hydroxyl.Conclusions: The
      results offer a mechanism-based therapeutic paradigm for disrupting the AR growth
      promoting axis in the spectrum of prostate tumors while reducing global
      suppression of testosterone actions. KCI807 offers a good lead molecule for drug
      development. Clin Cancer Res; 1-14. (c)2018 AACR.

PMID- 30185424
TI  - Proportionate and scientifically sound risk assessment of gene-edited plants.

PMID- 30185423
TI  - rebuff regulates apical luminal matrix to control tube size in Drosophila
      trachea.
AB  - The Drosophila embryonic tracheal network is an excellent model to study tube
      size. The chitin-based apical luminal matrix and cell polarity are well known to
      regulate tube size in Drosophila trachea. Defects in luminal matrix and cell
      polarity lead to tube overexpansion. Here, we address the novel function of the
      rebuff (reb) gene, which encodes an evolutionarily conserved Smad-like protein.
      In reb mutants, tracheal tubes are moderately over-elongated. Despite the
      establishment of normal cell polarity, we observed significantly reduced apical
      luminal matrix in reb mutants. Among various luminal components, luminal
      Obstructor-A (ObstA) is drastically reduced. Interestingly, ObstA is localized in
      vesicle-like structures that are apically concentrated in reb mutants. To
      investigate the possibility that reb is involved in the endocytosis of ObstA, we
      analyzed the co-localization of ObstA and endocytic markers in reb mutants. We
      observed that ObstA is localized in late endosomes and recycling endosomes. This
      suggests that in reb mutant trachea, endocytosed ObstA is degraded or recycled
      back to the apical region. However, ObstA vesicles are retained in the apical
      region and are failed to be secreted to the lumen. Taken together, these results
      suggest one function of reb is regulating the endocytosis of luminal matrix
      components.

PMID- 30185426
TI  - Estimating Asian Contribution to the Brazilian Population: A New Application of a
      Validated Set of 61 Ancestry Informative Markers.
AB  - Estimates of different ancestral proportions in admixed populations are very
      important in population genetics studies, especially for the detection of
      population substructure effects in studies of case-control associations. Brazil
      is one of the most heterogeneous countries in the world, both from a socio
      cultural and a genetic point of view. In this work, we investigated a previously
      developed set of 61 ancestry informative markers (AIM), aiming to estimate the
      proportions of four different ancestral groups (African, European, Native
      American and Asian) in Brazilian populations. To the best of our knowledge, this
      is the first study to use a set of AIM to investigate the genetic contribution of
      all four main parental populations to the Brazilian population, including Asian
      contribution. All selected markers were genotyped through multiplex PCR and
      capillary electrophoresis. The set was able to successfully differentiate the
      four ancestral populations (represented by 939 individuals) and identify their
      genetic contributions to the Brazilian population. In addition, it was used to
      estimate individual interethnic admixture of 1050 individuals from the Southeast
      region of Brazil and it showed that these individuals present a higher European
      ancestry contribution, followed by African, Asian and Native American ancestry
      contributions. Therefore, the 61 AIM set has proved to be a valuable tool to
      estimate individual and global ancestry proportions in populations mainly formed
      by these four groups. Our findings highlight the importance of using sets of AIM
      to evaluate population substructure in studies carried in admixed populations, in
      order to avoid misinterpretation of results.

PMID- 30185427
TI  - International Community Access to Child Health Program: 10 Years of Improving
      Child Health.

PMID- 30185425
TI  - Statins for primary prevention of cardiovascular events and mortality in old and
      very old adults with and without type 2 diabetes: retrospective cohort study.
AB  - OBJECTIVE: To assess whether statin treatment is associated with a reduction in
      atherosclerotic cardiovascular disease (CVD) and mortality in old and very old
      adults with and without diabetes. DESIGN: Retrospective cohort study. SETTING:
      Database of the Catalan primary care system (SIDIAP), Spain, 2006-15.
      PARTICIPANTS: 46 864 people aged 75 years or more without clinically recognised
      atherosclerotic CVD. Participants were stratified by presence of type 2 diabetes
      mellitus and as statin non-users or new users. MAIN OUTCOME MEASURES: Incidences
      of atherosclerotic CVD and all cause mortality compared using Cox proportional
      hazards modelling, adjusted by the propensity score of statin treatment. The
      relation of age with the effect of statins was assessed using both a categorical
      approach, stratifying the analysis by old (75-84 years) and very old (>=85 years)
      age groups, and a continuous analysis, using an additive Cox proportional hazard
      model. RESULTS: The cohort included 46 864 participants (mean age 77 years; 63%
      women; median follow-up 5.6 years). In participants without diabetes, the hazard
      ratios for statin use in 75-84 year olds were 0.94 (95% confidence interval 0.86
      to 1.04) for atherosclerotic CVD and 0.98 (0.91 to 1.05) for all cause mortality,
      and in those aged 85 and older were 0.93 (0.82 to 1.06) and 0.97 (0.90 to 1.05),
      respectively. In participants with diabetes, the hazard ratio of statin use in 75
      84 year olds was 0.76 (0.65 to 0.89) for atherosclerotic CVD and 0.84 (0.75 to
      0.94) for all cause mortality, and in those aged 85 and older were 0.82 (0.53 to
      1.26) and 1.05 (0.86 to 1.28), respectively. Similarly, effect analysis of age in
      a continuous scale, using splines, corroborated the lack of beneficial statins
      effect for atherosclerotic CVD and all cause mortality in participants without
      diabetes older than 74 years. In participants with diabetes, statins showed a
      protective effect against atherosclerotic CVD and all cause mortality; this
      effect was substantially reduced beyond the age of 85 years and disappeared in
      nonagenarians. CONCLUSIONS: In participants older than 74 years without type 2
      diabetes, statin treatment was not associated with a reduction in atherosclerotic
      CVD or in all cause mortality, even when the incidence of atherosclerotic CVD was
      statistically significantly higher than the risk thresholds proposed for statin
      use. In the presence of diabetes, statin use was statistically significantly
      associated with reductions in the incidence of atherosclerotic CVD and in all
      cause mortality. This effect decreased after age 85 years and disappeared in
      nonagenarians.

PMID- 30185428
TI  - Comprehensive Community-Based Intervention and Asthma Outcomes in African
      American Adolescents.
AB  - : : media-1vid110.1542/5804911922001PEDS-VA_2017-3737Video Abstract BACKGROUND:
      African American adolescents appear to be the most at risk for asthma morbidity
      and mortality even compared with other minority groups, yet there are few
      successful interventions for this population that are used to target poorly
      controlled asthma. METHODS: African American adolescents (age 12-16 years) with
      moderate-to-severe persistent asthma and >=1 inpatient hospitalization or >=2
      emergency department visits in 12 months were randomly assigned to Multisystemic
      Therapy-Health Care or an attention control group (N = 167). Multisystemic
      Therapy-Health Care is a 6-month home- and community-based treatment that has
      been shown to improve illness management and health outcomes in high-risk
      adolescents by addressing the unique barriers for each individual family with
      cognitive behavioral interventions. The attention control condition was weekly
      family supportive counseling, which was also provided for 6 months in the home.
      The primary outcome was lung function (forced expiratory volume in 1 second
      [FEV1]) measured over 12 months of follow-up. RESULTS: Linear mixed-effects
      models revealed that compared with adolescents in the comparison group,
      adolescents in the treatment group had significantly greater improvements in FEV1
      secondary outcomes of adherence to controller medication, and the frequency of
      asthma symptoms. Adolescents in the treatment group had greater reductions in
      hospitalizations, but there were no differences in reductions in emergency
      department visits. CONCLUSIONS: A comprehensive family- and community-based
      treatment significantly improved FEV1, medication adherence, asthma symptom
      frequency, and inpatient hospitalizations in African American adolescents with
      poorly controlled asthma. Further evaluation in effectiveness and implementation
      trials is warranted.

PMID- 30185430
TI  - Genotyping Polyploids from Messy Sequencing Data.
AB  - Detecting and quantifying the differences in individual genomes (i.e.,
      genotyping), plays a fundamental role in most modern bioinformatics pipelines.
      Many scientists now use reduced representation next-generation sequencing (NGS)
      approaches for genotyping. Genotyping diploid individuals using NGS is a well
      studied field, and similar methods for polyploid individuals are just emerging.
      However, there are many aspects of NGS data, particularly in polyploids, that
      remain unexplored by most methods. Our contributions in this paper are fourfold:
      (i) We draw attention to, and then model, common aspects of NGS data: sequencing
      error, allelic bias, overdispersion, and outlying observations. (ii) Many
      datasets feature related individuals, and so we use the structure of Mendelian
      segregation to build an empirical Bayes approach for genotyping polyploid
      individuals. (iii) We develop novel models to account for preferential pairing of
      chromosomes, and harness these for genotyping. (iv) We derive oracle genotyping
      error rates that may be used for read depth suggestions. We assess the accuracy
      of our method in simulations, and apply it to a dataset of hexaploid sweet potato
      (Ipomoea batatas). An R package implementing our method is available at
      https://cran.r-project.org/package=updog.

PMID- 30185431
TI  - A phase 2 study of ruxolitinib in combination with azacitidine in patients with
      myelofibrosis.
AB  - Ruxolitinib (RUX)-based combinations may provide benefit for patients with
      myelofibrosis (MF). In this open-label, nonrandomized, prospective phase 2 study,
      patients with MF initially received RUX twice per day continuously in 28-day
      cycles for the first 3 cycles. Azacitidine (AZA) 25 mg/m2 (days 1-5) was added
      starting with cycle 4 and could be subsequently increased to 75 mg/m2 (days 1-5).
      Forty-six patients were enrolled with a median follow-up of 28 months (range, 4
      50+ months). An International Working Group for Myelofibrosis Research and
      Treatment (IWG-MRT) response was achieved in 33 patients (72%), with a median
      time to response of 1.8 months (range, 0.7-19.0 months). One-fourth (7 of 33) of
      the IWG-MRT responses occurred after the addition of AZA. A reduction of >50% in
      palpable spleen length at 24 weeks and at any time on the study was achieved in
      62% and 71% of the evaluable patients, respectively. Among patients who achieved
      a >50% reduction in spleen length at 24 weeks, 95% had maintained it at 48 weeks.
      Notably, improvements in bone marrow reticulin fibrosis grade occurred in 57% of
      the patients at 24 months. Treatment discontinuations as a result of drug-related
      toxicities occurred in 4 patients (9%), all as a result of cytopenias. New onset
      grade 3 to 4 anemia and thrombocytopenia occurred in 35% and 26% of patients,
      respectively. RUX and AZA were safe, with encouraging spleen response rates and
      improvement in bone marrow fibrosis in patients with MF. This trial was
      registered at www.clinicaltrials.gov as #NCT01787487.

PMID- 30185432
TI  - How I use molecular genetic tests to evaluate patients who have or may have
      myelodysplastic syndromes.
AB  - Myelodysplastic syndromes (MDS) can be difficult to diagnose, especially when
      morphological changes in blood and marrow cells are minimal, myeloblast
      proportion is not increased, and the karyotype is normal. The discovery of >40
      genes that are recurrently somatically mutated in MDS patients raised hope that
      molecular genetic testing for these mutations might help clarify the diagnosis in
      ambiguous cases where patients present with cytopenias and nondiagnostic marrow
      morphological findings. However, many older healthy individuals also harbor
      somatic mutations in leukemia-associated driver genes, especially in DNMT3A,
      TET2, and ASXL1, and detection of common aging-associated mutations in a
      cytopenic patient can cause diagnostic uncertainty. Despite this potential
      confounding factor, certain somatic mutation patterns when observed in cytopenic
      patients confer a high likelihood of disease progression and may allow a
      provisional diagnosis of MDS even if morphologic dysplasia and other diagnostic
      criteria are absent. A subset of acquired mutations also influences risk
      stratification of patients with an established MDS diagnosis and can inform
      treatment selection. Many unanswered questions remain about the implications of
      specific mutations, and clinicians also vary widely in their comfort with
      interpreting sequencing results. Here, I review the use of molecular genetic
      assays in patients with possible MDS or diagnosed MDS.

PMID- 30185433
TI  - Impact of monomeric, oligomeric and fibrillar alpha-synuclein on astrocyte
      reactivity and toxicity to neurons.
AB  - Synucleinopathies are a group of neurodegenerative disorders characterized by the
      presence of aggregated and fibrillar forms of alpha-synuclein (alpha-syn). Here,
      we analyze the effect of different species of alpha-syn, including monomeric,
      oligomeric and fibrillar forms of the protein, on rat astrocytes. Astrocytes
      treated with these distinct forms of alpha-syn showed an increase in long and
      thin processes and glial fibrillary acidic protein expression, indicating cell
      activation, high levels of intracellular oxidants and increased expression of
      cytokines. Moreover, astrocytes incubated with the different species induced
      hippocampal neuronal death in co-culture, and cytotoxicity was particularly
      enhanced by exposure to fibrillar alpha-syn. Further exploration of the
      mechanisms behind astrocyte activation and cytotoxicity revealed differences
      between the assessed alpha-syn species. Only oligomers induced mitochondrial
      dysfunction in astrocytes and significantly increased extracellular hydrogen
      peroxide production by these cells. Besides, TNF-alpha and IL-1beta (interleukin
      1beta) expression presented different kinetics and levels depending on which
      species induced the response. Our data suggest that alpha-syn species (monomeric,
      oligomeric and fibrillar) induce astrocyte activation that can lead to neuronal
      death. Nevertheless, the tested alpha-syn species act through different
      preferential mechanisms and potency. All together these results help to
      understand the effect of alpha-syn species on astrocyte function and their
      potential impact on the pathogenesis of Parkinson's disease and related alpha
      synucleinopathies.

PMID- 30185434
TI  - IQGAP1 binds the Axl receptor kinase and inhibits its signaling.
AB  - Axl is a tyrosine kinase receptor that is important for hematopoiesis, the innate
      immune response, platelet aggregation, engulfment of apoptotic cells and cell
      survival. Binding of growth arrest-specific protein 6 (Gas6) activates Axl
      signaling, but the mechanism of inactivation of the Axl receptor is poorly
      understood. In the present study, we show that IQGAP1 modulates Axl signaling.
      IQGAP1 is a scaffold protein that integrates cell signaling pathways by binding
      several growth factor receptors and intracellular signaling molecules. Our in
      vitro analysis revealed a direct interaction between the IQ domain of IQGAP1 and
      Axl. Analysis by both immunoprecipitation and proximity ligation assays
      demonstrated an association between Axl and IQGAP1 in cells and this interaction
      was decreased by Gas6. Unexpectedly, reducing IQGAP1 levels in cells
      significantly enhanced the ability of Gas6 to stimulate both Axl phosphorylation
      and activation of Akt. Moreover, IQGAP1 regulates the interaction of Axl with the
      epidermal growth factor receptor. Our data identify IQGAP1 as a previously
      undescribed suppressor of Axl and provide insight into regulation of Axl
      function.

PMID- 30185429
TI  - Multiple Histone Methyl-Lysine Readers Ensure Robust Development and Germline
      Immortality in Caenorhabditis elegans.
AB  - Chromatin modifications, including methylation of histone H3 at lysine 27
      (H3K27me) by the Polycomb group proteins, play a broadly conserved role in the
      maintenance of cell fate. Diverse chromatin organization modifier (chromo) domain
      proteins act as "readers" of histone methylation states. However, understanding
      the functional relationships among chromo domains and their roles in the
      inheritance of gene expression patterns remains challenging. Here, we identify
      two chromo-domain proteins, CEC-1 and CEC-6, as potential readers of H3K27me in
      Caenorhabditis elegans, where they have divergent expression patterns and
      contribute to distinct phenotypes. Both cec-1 and cec-6 genetically interact with
      another chromo-domain gene, cec-3, a reader of H3K9 methylation. Combined loss of
      cec-1 and cec-3 leads to developmental defects in the adult that result in
      decreased fitness. Furthermore, loss of cec-6 and cec-3 surprisingly leads to a
      progressive loss of fertility across generations, a "mortal germline" phenotype.
      Our results provide evidence of functional compensation between H3K27me and
      H3K9me heterochromatin pathways, and show that histone methylation readers
      contribute to both somatic development and transgenerational fitness.

PMID- 30185435
TI  - Use of Mid-Upper Arm Circumference by Novel Community Platforms to Detect,
      Diagnose, and Treat Severe Acute Malnutrition in Children: A Systematic Review.
AB  - BACKGROUND: A stubborn persistence of child severe acute malnutrition (SAM) and
      continued gaps in program coverage have made identifying methods for expanding
      detection, diagnosis, and treatment of SAM an urgent public health need. There is
      growing consensus that making mid-upper arm circumference (MUAC) use more widely
      accessible among caregivers and community health workers (CHWs) is an important
      next step in further decentralizing SAM care and increasing program coverage,
      including the ability of CHWs to treat uncomplicated SAM in community settings.
      METHODS: We conducted a systematic review to summarize published and operational
      evidence published since 2000 describing the use of MUAC for detection and
      diagnosis of SAM in children aged 6-59 months by caregivers and CHWs, and of
      management of uncomplicated SAM by CHWs, all outside of formal health care
      settings. We screened 1,072 records, selected 43 records for full-text screening,
      and identified 22 studies that met our eligibility criteria. We extracted data on
      a number of items, including study design, strengths, and weaknesses;
      intervention and control; and key findings and operational lessons. We then
      synthesized the qualitative findings to inform our conclusions. The issue of
      treating children classified as SAM based on low weight-for-height, rather than
      MUAC, at household level, is not addressed in this review. FINDINGS: We found
      evidence that caregivers are able to use MUAC to detect SAM in their children
      with minimal risk and many potential benefits to early case detection and
      coverage. We also found evidence that CHWs are able to correctly use MUAC for SAM
      detection and diagnosis and to provide a high quality of care in the treatment of
      uncomplicated SAM when training, supervision, and motivation are adequate.
      However, the number of published research studies was small, their geographic
      scope was narrow, and most described intensive, small-scale interventions; thus,
      findings are not currently generalizable to public-sector health care systems.
      CONCLUSIONS: Scaling up the use of MUAC by caregivers and CHWs to detect SAM in
      household and community settings is a promising step toward improving the
      coverage of SAM detection, diagnosis, and treatment. Further research on
      scalability, applicability across a wider range of contexts, coverage impact, and
      cost is needed. The primary use of MUAC for SAM detection should also be explored
      where appropriate.

PMID- 30185436
TI  - Alterations in platelet secretion differentially affect thrombosis and
      hemostasis.
AB  - We genetically manipulated the major platelet vesicle-associated membrane
      proteins (VAMP2, VAMP3, and VAMP8) to create mice with varying degrees of
      disrupted platelet secretion. As previously shown, loss of VAMP8 reduced granule
      secretion, and this defect was exacerbated by further deletion of VAMP2 and
      VAMP3. VAMP2Delta3Delta8-/- platelets also had reduced VAMP7. Loss of VAMP2 and
      VAMP3 (VAMP2Delta3Delta) had a minimal impact on secretion when VAMP7 and VAMP8
      were present. Integrin alphaIIbbeta3 activation and aggregation were not
      affected, although spreading was reduced in VAMP2Delta3Delta8-/- platelets. Using
      these mice as tools, we asked how much secretion is needed for proper thrombosis
      and hemostasis in vivo. VAMP2Delta3Delta mice showed no deficiency, whereas VAMP8
      /- mice had attenuated formation of occlusive thrombi upon FeCl3-induced arterial
      injury but no excessive bleeding upon tail transection. VAMP2Delta3Delta8-/- mice
      bled profusely and failed to form occlusive thrombi. Plasma-coagulation factors
      were normal in all of the strains, but phosphatidylserine exposure was reduced in
      VAMP2Delta3Delta and VAMP2Delta3Delta8-/- platelets. From our data, an ~40% to
      50% reduction in platelet secretion in vitro (dense and alpha granule) correlated
      with reduced occlusive thrombosis but no compromise in hemostasis. At a >50%
      reduction, thrombosis and hemostasis were defective in vivo. Our studies are the
      first systematic manipulation of platelet exocytic machinery to demonstrate a
      quantitative linkage between in vitro platelet secretion and hemostasis and
      thrombosis in vivo. The animals described will be invaluable tools for future
      investigations into how platelet secretion affects other vascular processes.

PMID- 30185438
TI  - Steroids prevent early recurrence of atrial fibrillation following catheter
      ablation: a systematic review and meta-analysis.
AB  - Previous studies have reported that steroids may reduce the risk of atrial
      fibrillation (AF) recurrence after catheter ablation, but data regarding this
      issue have been controversial. Therefore, we conducted a meta-analysis of
      randomized clinical trials (RCTs) and observational studies to ascertain the
      association of steroids and AF recurrence after ablation. PubMed, Embase, and
      Cochrane online databases were searched from inception to December 2017. The
      primary outcome of the meta-analysis was short-term or long-term AF recurrence
      following a single ablation procedure with or without the use of steroids. Both
      fixed- and random-effects models were used to calculate the overall effect
      estimates. Eight studies (four RCTs and four observational studies), with a total
      992 patients, were included in the present study. Our meta-analysis shows that
      steroid use was associated with reduced AF occurrence at 3 months (odd ratio (OR)
      = 0.53, 95% confidence interval (CI) = 0.31-0.90, P=0.02) and 12-14 months (OR =
      0.67, 95% CI = 0.47-0.95, P=0.02) after radiofrequency (RF) catheter ablation
      (RFCA). No clear benefit was observed for AF recurrence at 2-3 days, 1 or 24
      months of follow-up. Steroid use was associated with decreased risk of early AF
      recurrence 3 and 12-14 months after ablation. No clear relationship was observed
      for 2-3 days, 1 and 24 months of follow-up and further data are needed to clarify
      these results.

PMID- 30185437
TI  - STAT5 is essential for IL-7-mediated viability, growth, and proliferation of T
      cell acute lymphoblastic leukemia cells.
AB  - T-cell acute lymphoblastic leukemia (T-ALL) constitutes an aggressive subset of
      ALL, the most frequent childhood malignancy. Whereas interleukin-7 (IL-7) is
      essential for normal T-cell development, it can also accelerate T-ALL development
      in vivo and leukemia cell survival and proliferation by activating
      phosphatidylinositol 3-kinase/protein kinase B/mechanistic target of rapamycin
      signaling. Here, we investigated whether STAT5 could also mediate IL-7 T-ALL
      promoting effects. We show that IL-7 induces STAT pathway activation in T-ALL
      cells and that STAT5 inactivation prevents IL-7-mediated T-ALL cell viability,
      growth, and proliferation. At the molecular level, STAT5 is required for IL-7
      induced downregulation of p27kip1 and upregulation of the transferrin receptor,
      CD71. Surprisingly, STAT5 inhibition does not significantly affect IL-7-mediated
      Bcl-2 upregulation, suggesting that, contrary to normal T-cells, STAT5 promotes
      leukemia cell survival through a Bcl-2-independent mechanism. STAT5 chromatin
      immunoprecipitation sequencing and RNA sequencing reveal a diverse IL-7-driven
      STAT5-dependent transcriptional program in T-ALL cells, which includes BCL6
      inactivation by alternative transcription and upregulation of the oncogenic
      serine/threonine kinase PIM1 Pharmacological inhibition of PIM1 abrogates IL-7
      mediated proliferation on T-ALL cells, indicating that strategies involving the
      use of PIM kinase small-molecule inhibitors may have therapeutic potential
      against a majority of leukemias that rely on IL-7 receptor (IL-7R) signaling.
      Overall, our results demonstrate that STAT5, in part by upregulating PIM1
      activity, plays a major role in mediating the leukemia-promoting effects of IL
      7/IL-7R.

PMID- 30185439
TI  - Circulating level of fibroblast growth factor 21 is independently associated with
      the risks of unstable angina pectoris.
AB  - There is increasing evidence that serum adipokine levels are associated with
      higher risks of cardiovascular diseases. As an important adipokine, fibroblast
      growth factor 21 (FGF21) has been demonstrated to be associated with
      atherosclerosis and coronary artery disease (CAD). However, circulating level of
      FGF21 in patients with angina pectoris has not yet been investigated. Circulating
      FGF21 level was examined in 197 patients with stable angina pectoris (SAP, n=66),
      unstable angina pectoris (UAP, n=76), and control subjects (n=55) along with
      clinical variables of cardiovascular risk factors. Serum FGF21 concentrations on
      admission were significantly increased more in patients with UAP than those with
      SAP (Ln-FGF21: 5.26 +/- 0.87 compared with 4.85 +/- 0.77, P<0.05) and control
      subjects (natural logarithm (Ln)-FGF21: 5.26 +/- 0.87 compared with 4.54 +/-
      0.72, P<0.01). The correlation analysis revealed that serum FGF21 concentration
      was positively correlated with the levels of cardiac troponin I (cTnI) (r2  = 
      0.026, P=0.027) and creatine kinase-MB (CK-MB) (r2  =  0.023, P= 0.04).
      Furthermore, FGF21 level was identified as an independent factor associated with
      the risks of UAP (odds ratio (OR): 2.781; 95% CI: 1.476-5.239; P=0.002), after
      adjusting for gender, age, and body mass index (BMI). However, there were no
      correlations between serum FGF21 levels and the presence of SAP (OR: 1.248; 95%
      CI: 0.703-2.215; P=0.448). The present study indicates that FGF21 has a strong
      correlation and precise predictability for increased risks of UAP, that is
      independent of traditional risk factors of angina pectoris.

PMID- 30185440
TI  - The Patterned Structure of Galactoglucomannan Suggests It May Bind to Cellulose
      in Seed Mucilage.
AB  - The interaction between mannan polysaccharides and cellulose microfibrils
      contributes to cell wall properties in some vascular plants, but the molecular
      arrangement of mannan in the cell wall and the nature of the molecular bonding
      between mannan and cellulose remain unknown. Previous studies have shown that
      mannan is important in maintaining Arabidopsis (Arabidopsis thaliana) seed
      mucilage architecture, and that Cellulose Synthase-Like A2 (CSLA2) synthesizes a
      glucomannan backbone, which Mannan alpha-Galactosyl Transferase1
      (MAGT1/GlycosylTransferase-Like6/Mucilage Related10) might decorate with single
      alpha-Gal branches. Here, we investigated the ratio and sequence of Man and Glc
      and the arrangement of Gal residues in Arabidopsis mucilage mannan using enzyme
      sequential digestion, carbohydrate gel electrophoresis, and mass spectrometry. We
      found that seed mucilage galactoglucomannan has a backbone consisting of the
      repeating disaccharide [4)-beta-Glc-(1,4)-beta-Man-(1,], and most of the Man
      residues in the backbone are substituted by single alpha-1,6-Gal. CSLA2 is
      responsible for the synthesis of this patterned glucomannan backbone and MAGT1
      catalyses the addition of alpha-Gal. In vitro activity assays revealed that MAGT1
      transferred alpha-Gal from UDP-Gal only to Man residues within the CSLA2
      patterned glucomannan backbone acceptor. These results indicate that CSLAs and
      galactosyltransferases are able to make precisely defined galactoglucomannan
      structures. Molecular dynamics simulations suggested this patterned
      galactoglucomannan is able to bind stably to some hydrophilic faces and to
      hydrophobic faces of cellulose microfibrils. A specialization of the biosynthetic
      machinery to make galactoglucomannan with a patterned structure may therefore
      regulate the mode of binding of this hemicellulose to cellulose fibrils.

PMID- 30185441
TI  - Actin Reorganization Triggers Rapid Cell Elongation in Roots.
AB  - Root growth is controlled by mechanisms underlying cell division and cell
      elongation, which respond to various internal and external factors. In
      Arabidopsis (Arabidopsis thaliana), cells produced in the proximal meristem (PM)
      elongate and differentiate in the transition zone (TZ) and the
      elongation/differentiation zone (EDZ). Previous studies have demonstrated that
      endoreplication is involved in root cell elongation; however, the manner by which
      cells increase in length by more than 2-fold remains unknown. Here, we show that
      epidermal and cortical cells in Arabidopsis roots undergo two modes of rapid cell
      elongation: the first rapid cell elongation occurs at the border of the proximal
      meristem and the TZ, and the second mode occurs during the transition from the TZ
      to the EDZ. Our previous study showed that cytokinin signaling promotes
      endoreplication, which triggers the first rapid cell elongation. Our cytological
      and genetic data revealed that the second rapid cell elongation involves dynamic
      actin reorganization independent of endoreplication. Cytokinins promote actin
      bundling and the resultant second rapid cell elongation through activating the
      signaling pathway involving the cytokinin receptors ARABIDOPSIS HISTIDINE KINASE3
      (AHK3) and AHK4 and the B-type transcription factor ARABIDOPSIS RESPONSE
      REGULATOR2. Our results suggest that cytokinins promote the two modes of rapid
      cell elongation by controlling distinct cellular events: endoreplication and
      actin reorganization.

PMID- 30185442
TI  - MKK6 Functions in Two Parallel MAP Kinase Cascades in Immune Signaling.
AB  - Arabidopsis (Arabidopsis thaliana) MAP KINASE (MPK) proteins can function in
      multiple MAP kinase cascades and physiological processes. For instance, MPK4
      functions in regulating development as well as in plant defense by participating
      in two independent MAP kinase cascades: the MEKK1-MKK1/MKK2-MPK4 cascade promotes
      basal resistance against pathogens and is guarded by the NB-LRR protein SUMM2,
      whereas the ANPs-MKK6-MPK4 cascade plays an essential role in cytokinesis. Here,
      we report a novel role for MKK6 in regulating plant immune responses. We found
      that MKK6 functions similarly to MKK1/MKK2 and works together with MEKK1 and MPK4
      to prevent autoactivation of SUMM2-mediated defense responses. Interestingly,
      loss of MKK6 or ANP2/ANP3 results in constitutive activation of plant defense
      responses. The autoimmune phenotypes of mkk6 and anp2 anp3 mutant plants can be
      largely suppressed by a constitutively active mpk4 mutant. Further analysis
      showed that the constitutive defense response in anp2 anp3 is dependent on the
      defense regulators PAD4 and EDS1, but not on SUMM2, suggesting that the ANP2/ANP3
      MKK6-MPK4 cascade may be guarded by a TIR-NB-LRR protein. Our study shows that
      MKK6 has multiple functions in plant defense responses in addition to
      cytokinesis.

PMID- 30185443
TI  - Lung cancer risk and occupational exposures in crop farming: results from the
      AGRIculture and CANcer (AGRICAN) cohort.
AB  - OBJECTIVES: Farmers are considered at lower risk of lung cancer. However,
      specific tasks can expose them to hazardous air contaminants such as pesticides,
      diesel exhaust and mineral dust. This study aimed to assess the associations
      between various crops and related tasks and the risk of lung cancer, overall and
      by histological subtypes. METHODS: AGRIculture and CANcer is a prospective French
      cohort of individuals affiliated to the agricultural health insurance scheme.
      Incident lung cancers (n=897) were identified by cancer registries from enrolment
      (2005-2007) to 2013. Data on crop and livestock exposure during lifetime were
      obtained from the enrolment questionnaire. We used a Cox model with attained age
      as timescale, adjusted for gender, smoking history and exposure to cattle and
      horses. Effects of duration and surface were assessed and analyses stratified on
      gender and smoking status were performed. RESULTS: Winegrowers were at higher
      risk of adenocarcinoma (HR=1.27 (95% CI 0.94 to 1.72)). We also found an
      association between pea growing and small cell lung cancer: significant effect of
      duration (ptrend=0.04) and the suggestion of a surface-effect relationship
      (ptrend=0.06); increased risk (HR=2.38 (95% CI 1.07 to 5.28)) for pesticide
      users; and significant effect of duration (ptrend=0.01) for harvesters. The risk
      of squamous cell carcinoma was increased for sunflower growing (HR=1.59 (95% CI
      0.97 to 2.62), fruit-tree pruning (HR=1.44 (95% CI 0.92 to 2.27)) and pesticide
      use on beets (HR=1.47 (95% CI 0.92 to 2.34)). Corn and/or wheat/barley growers
      were at lower risk of lung cancer. CONCLUSIONS: Our results suggest associations
      between lung cancer and several crop-related tasks, even if we cannot rule out
      some chance findings due to multiple comparisons.

PMID- 30185444
TI  - Incorporating sleep medicine content into medical school through neuroscience
      core curricula.
AB  - OBJECTIVE: To present (1) justification for earmarking sleep medicine education
      as an essential component of all medical school curricula and (2) various avenues
      to incorporate sleep medicine exposure into medical school curricula through
      (primarily) neuroscience and neurology courses. METHODS: Per consensus of a team
      of leading neurology and sleep medicine educators, an evidence-based rationale
      for including sleep medicine across a 4-year medical school curriculum is
      presented along with suggested content, available/vetted resources, and formats
      for delivering sleep medicine education at various points and through various
      formats. RESULTS: Growing evidence has linked sleep disorders (e.g., sleep
      disordered breathing, chronic insufficient sleep) as risk factors for several
      neurologic disorders. Medical educators in neurology/neuroscience are now
      strongly advocating for sleep medicine education in the context of
      neurology/neuroscience pre and post graduate medical education. Sleep medicine
      education is also a critical component of a proactive strategy to address
      physician wellness and burnout. The suggested curriculum proposes a sleep
      educational exposure time of 2-4 hours per year in the form of lectures, flipped
      classroom sessions, clinical opportunities, and online educational tools that
      would result in a 200%-400% increase in the amount of sleep medicine exposure
      that US medical schools currently provide. The guidelines are accompanied by the
      recommendation for use of technological education, to facilitate more seamless
      curricular incorporation. CONCLUSION: Even in this era with limited flexibility
      to add content to an already packed medical school curriculum, incorporating
      sleep medicine exposure into the current medical school curriculum is both
      justified and feasible.

PMID- 30185445
TI  - A sleep medicine medical school curriculum: Time for us to wake up.

PMID- 30185446
TI  - Antiepileptic drug clearances during pregnancy and clinical implications for
      women with epilepsy.
AB  - OBJECTIVE: To characterize the magnitude and time course of pregnancy-related
      clearance changes for different antiepileptic drugs (AEDs): levetiracetam,
      oxcarbazepine, topiramate, phenytoin, and valproate. A secondary aim was to
      determine if a decreased AED serum concentration was associated with increased
      seizure frequency. METHODS: Women with epilepsy were enrolled preconception or
      early in pregnancy and prospectively followed throughout pregnancy and the first
      postpartum year with daily diaries of AED doses, adherence, and seizures. Study
      visits with AED concentration measurements occurred every 1-3 months. AED
      clearances in each trimester were compared to nonpregnant baseline using a mixed
      linear regression model, with adjustments for age, race, and hours postdose. In
      women on monotherapy, 2-sample t test was used to compare the ratio to target
      concentrations (RTC) between women with seizure worsening each trimester and
      those without. RESULTS: AED clearances were calculated for levetiracetam (n = 18
      pregnancies), oxcarbazepine (n = 4), topiramate (n = 10), valproate (n = 5), and
      phenytoin (n = 7). Mean maximal clearances were reached for (1) levetiracetam in
      first trimester (1.71-fold baseline clearance) (p = 0.0001), (2) oxcarbazepine in
      second trimester (1.63-fold) (p = 0.0001), and (3) topiramate in second trimester
      (1.39-fold) (p = 0.025). In 15 women on AED monotherapy, increased seizure
      frequency in the first, second, and all trimesters was associated with a lower
      RTC (p < 0.05). CONCLUSION: AED clearance significantly changes by the first
      trimester for levetiracetam and by the second trimester for oxcarbazepine and
      topiramate. Lower RTC was associated with seizure worsening. Early therapeutic
      drug monitoring and dose adjustment may be helpful to avoid increased seizure
      frequency.

PMID- 30185447
TI  - BOLD cerebrovascular reactivity as a novel marker for crossed cerebellar
      diaschisis.
AB  - OBJECTIVE: To study blood oxygen level-dependent cerebrovascular reactivity (BOLD
      CVR) as a surrogate imaging marker for crossed cerebellar diaschisis (CCD).
      METHODS: Twenty-five participants with symptomatic unilateral cerebrovascular
      steno-occlusive disease underwent a BOLD-CVR and an acetazolamide challenged
      (15O)-H2O-PET study. CCD and cerebellar asymmetry index were determined from PET
      and compared to BOLD-CVR quantitative values. Neurologic status at admission and
      outcome after 3 months were determined with NIH Stroke Scale (NIHSS) and modified
      Rankin Scale (mRS) scores. RESULTS: For both the BOLD-CVR and PET examination, a
      significant cerebellar asymmetry index was found for participants exhibiting CCD
      (CCD+ vs CCD-: for BOLD-CVR 13.11 +/- 9.46 vs 1.52 +/- 4.97, p < 0.001; and for
      PET 7.31 +/- 2.75 vs 1.68 +/- 2.98, p < 0.001). The area under the curve for BOLD
      CVR was 0.89 (95% confidence interval: 0.75-1.0) with 0.91 sensitivity and 0.81
      specificity to detect CCD. Participants exhibiting CCD were in poorer clinical
      condition at baseline (CCD+ vs CCD-: NIHSS 7 vs 1, p = 0.003; mRS 3 vs 1, p =
      0.001) and after 3-month follow-up (NIHSS 2 vs 0, p = 0.02; mRS 1 vs 0, p =
      0.04). Worse performance on both scores showed an agreement with a larger BOLD
      CVR cerebellar asymmetry index. This was not found for PET. CONCLUSIONS: BOLD-CVR
      demonstrates similar sensitivity to detect CCD as compared to (15O)-H2O-PET in
      patients with symptomatic unilateral cerebrovascular steno-occlusive disease.
      Furthermore, participants exhibiting CCD had a poorer baseline neurologic
      performance and neurologic outcome at 3 months. CLASSIFICATION OF EVIDENCE: This
      study provides Class II evidence that BOLD-CVR identifies CCD in patients with
      symptomatic unilateral cerebrovascular steno-occlusive disease.

PMID- 30185448
TI  - Cannabis analgesia in chronic neuropathic pain is associated with altered brain
      connectivity.
AB  - OBJECTIVE: To characterize the functional brain changes involved in delta-9
      tetrahydrocannabinol (THC) modulation of chronic neuropathic pain. METHODS:
      Fifteen patients with chronic radicular neuropathic pain participated in a
      randomized, double-blind, placebo-controlled trial employing a counterbalanced,
      within-subjects design. Pain assessments and functional resting state brain scans
      were performed at baseline and after sublingual THC administration. We examined
      functional connectivity of the anterior cingulate cortex (ACC) and pain-related
      network dynamics using graph theory measures. RESULTS: THC significantly reduced
      patients' pain compared to placebo. THC-induced analgesia was correlated with a
      reduction in functional connectivity between the anterior cingulate cortex (ACC)
      and the sensorimotor cortex. Moreover, the degree of reduction was predictive of
      the response to THC. Graph theory analyses of local measures demonstrated
      reduction in network connectivity in areas involved in pain processing, and
      specifically in the dorsolateral prefrontal cortex (DLPFC), which were correlated
      with individual pain reduction. CONCLUSION: These results suggest that the ACC
      and DLPFC, 2 major cognitive-emotional modulation areas, and their connections to
      somatosensory areas, are functionally involved in the analgesic effect of THC in
      chronic pain. This effect may therefore be mediated through induction of
      functional disconnection between regulatory high-order affective regions and the
      sensorimotor cortex. Moreover, baseline functional connectivity between these
      brain areas may serve as a predictor for the extent of pain relief induced by
      THC.

PMID- 30185449
TI  - Electrical impedance tomography effectively used in a case of paediatric
      pulmonary Langerhans cell histiocytosis.
AB  - A 2-year-old boy with severe pulmonary Langerhans cell histiocytosis presented in
      extreme respiratory failure. He was intubated and ventilated. Despite maximal
      support, he deteriorated and needed extremely high ventilator pressures. An
      electrical impedance tomography monitor was used to inform management. This is a
      monitoring technique which is not used in children due to the lack of suitable
      interface devices and a lack of randomised clinical evidence. Despite technical
      difficulties, a good signal was achieved. This informed management and enabled
      the selection of a suitable ventilator strategy, facilitating weaning. Electrical
      impedance tomography is a viable technology for use in paediatric critical
      respiratory failure. This is a non-invasive and safe technology which adds
      individual patient information which is not available through any other
      modalities. We urge equipment manufacturers to develop belts which will allow
      routine application of this life-saving technology in children.

PMID- 30185450
TI  - Cervical aortic arch: an unusual cause of a pulsatile neck mass.
AB  - A 72-year-old man presented with epistaxis on two occasions requiring admission.
      Prior to performing a bilateral sphenopalatine artery ligation diathermy,
      anaesthetic concern was raised regarding what the patient described as a
      'congenital aortic aneurysm', with an overlying scar secondary to explorative
      surgery as a child. The abnormality was a cervical aortic arch (CAA). CAA is a
      rare vascular anomaly, which most commonly manifests as a pulsatile neck mass. In
      this case, we discuss the differential diagnosis for a pulsatile neck mass and
      considerations to be made in the workup. We also highlight the importance of
      cardiovascular risk factor management in patients with CAA.

PMID- 30185451
TI  - Unusual ocular manifestations following viper bite.
AB  - We report a case of a 70-year-old farmer admitted for viper bite who presented
      with bilateral hyphema and angle closure attack. He was managed conservatively
      with topical steroids and cycloplegics. He responded well and was discharged
      after 2 weeks.

PMID- 30185452
TI  - Effect of topiramate on sweat chloride level while screening for cystic fibrosis.
AB  - Cystic fibrosis is the most common life-limiting genetic condition in Caucasians
      caused by Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene
      mutations. Sweat chloride is the current gold standard for diagnosis where values
      >60 mmol/L are diagnostic and values >30 mmol/L are indeterminate. There is
      limited literature on the effect of medications on the sweat chloride values. We
      report a case of topiramate being responsible for false-positive testing which
      resulted in overutilisation of medical resources and psychosocial stress on the
      family. Topiramate should be considered during the interpretation of the gold
      standard testing as one of the cause of false-positive sweat tests.

PMID- 30185453
TI  - Improvement in lung function following medialisation thyroplasty in a
      postbilateral lung transplant patient.
AB  - A 59-year-old man underwent external medialisation thyroplasty for his left
      unilateral vocal cord paralysis (UVCP) secondary to recent thoracic surgery. The
      patient had undergone bilateral lung transplant for idiopathic pulmonary fibrosis
      and was referred to the ear, nose and throat surgical team with new-onset voice
      hoarseness. Examination confirmed left UVCP, and after failing conservative
      management a decision was made to perform external medialisation thyroplasty.
      Following an uneventful procedure, the patient's phonation returned to normal,
      and remarkably on spirometry there was evidence of significant improvement in
      lung function. Despite case series demonstrating subjective improvement in
      respiration, this is the first documented case, to our knowledge, of significant
      improvement in spirometry following this procedure.

PMID- 30185454
TI  - Autism and trichotillomania in an adolescent boy.
AB  - An adolescent with autism spectrum disorder and improperly treated attention
      deficit hyperactivity disorder presented with recurrent hair pulling. Treatment
      with selective serotonin reuptake inhibitor and stimulant improved these
      conditions.

PMID- 30185455
TI  - Staring at the stars: a case of gastrointestinal basidiobolomycosis from the
      Indian subcontinent.

PMID- 30185456
TI  - Pulmonary artery sarcoma mimicking pulmonary embolism.

PMID- 30185457
TI  - An improvement in the method used to assess discriminatory ability when
      predicting the chances of a live birth after one or more complete cycles of in
      vitro fertilisation.

PMID- 30185458
TI  - Sexual function and cardiovascular disease: what the general cardiologist needs
      to know.

PMID- 30185460
TI  - Control of Sleep Onset by Shal/Kv4 Channels in Drosophila Circadian Neurons.
AB  - Sleep is highly conserved across animal species. Both wake- and sleep-promoting
      neurons are implicated in the regulation of wake-sleep transition at dusk in
      Drosophila However, little is known about how they cooperate and whether they act
      via different mechanisms. Here, we demonstrated that in female Drosophila, sleep
      onset was specifically delayed by blocking the Shaker cognate L channels [Shal;
      also known as voltage-gated K+ channel 4 (Kv4)] in wake-promoting cells,
      including large ventral lateral neurons (l-LNvs) and pars intercerebralis (PI),
      but not in sleep-promoting dorsal neurons (DN1s). Delayed sleep onset was also
      observed in males by blocking Kv4 activity in wake-promoting neurons.
      Electrophysiological recordings show that Kv4 channels contribute A-type currents
      in LNvs and PI cells, but are much less conspicuous in DN1s. Interestingly,
      blocking Kv4 in wake-promoting neurons preferentially increased firing rates at
      dusk ~ZT13, when the resting membrane potentials and firing rates were at lower
      levels. Furthermore, pigment-dispersing factor (PDF) is essential for the
      regulation of sleep onset by Kv4 in l-LNvs, and downregulation of PDF receptor
      (PDFR) in PI neurons advanced sleep onset, indicating Kv4 controls sleep onset
      via regulating PDF/PDFR signaling in wake-promoting neurons. We propose that Kv4
      acts as a sleep onset controller by suppressing membrane excitability in a clock
      dependent manner to balance the wake-sleep transition at dusk. Our results have
      important implications for the understanding and treatment of sleep disorders
      such as insomnia.SIGNIFICANCE STATEMENT The mechanisms by which our brains
      reversibly switch from waking to sleep state remain an unanswered and intriguing
      question in biological research. In this study, we identified that Shal/Kv4, a
      well known voltage-gated K+ channel, acts as a controller of wake-sleep
      transition at dusk in Drosophila circadian neurons. We find that interference of
      Kv4 function with a dominant-negative form (DNKv4) in subsets of circadian
      neurons specifically disrupts sleep onset at dusk, although Kv4 itself does not
      exhibit circadian oscillation. Kv4 preferentially downregulates neuronal firings
      at ZT9-ZT17, supporting that it plays an essential role in wake-sleep transition
      at dusk. Our findings may help understand and eventually treat sleep disorders
      such as insomnia.

PMID- 30185459
TI  - Divergent Prelimbic Cortical Pathways Interact with BDNF to Regulate Cocaine
      seeking.
AB  - A single BDNF microinfusion into prelimbic (PrL) cortex immediately after the
      last cocaine self-administration session decreases relapse to cocaine-seeking.
      The BDNF effect is blocked by NMDAR antagonists. To determine whether synaptic
      activity in putative excitatory projection neurons in PrL cortex is sufficient
      for BDNF's effect on relapse, the PrL cortex of male rats was infused with an
      inhibitory Designer Receptor Exclusively Activated by Designer Drugs (DREADD)
      viral vector driven by an alphaCaMKII promoter. Immediately after the last
      cocaine self-administration session, rats were injected with clozapine-N-oxide 30
      min before an intra-PrL BDNF microinfusion. DREADD-mediated inhibition of the PrL
      cortex blocked the BDNF-induced decrease in cocaine-seeking after abstinence and
      cue-induced reinstatement after extinction. Unexpectedly, DREADD inhibition of
      PrL neurons in PBS-infused rats also reduced cocaine-seeking, suggesting that
      divergent PrL pathways affect relapse. Next, using a cre-dependent retroviral
      approach, we tested the ability of DREADD inhibition of PrL projections to the
      NAc core or the paraventricular thalamic nucleus (PVT) to alter cocaine-seeking
      in BDNF- and PBS-infused rats. Selective inhibition of the PrL-NAc pathway at the
      end of cocaine self-administration blocked the BDNF-induced decrease in cocaine
      seeking but had no effect in PBS-infused rats. In contrast, selective inhibition
      of the PrL-PVT pathway in PBS-infused rats decreased cocaine-seeking, and this
      effect was prevented in BDNF-infused rats. Thus, activity in the PrL-NAc pathway
      is responsible for the therapeutic effect of BDNF on cocaine-seeking whereas
      inhibition of activity in the PrL-pPVT pathway elicits a similar therapeutic
      effect in the absence of BDNF.SIGNIFICANCE STATEMENT The major issue in cocaine
      addiction is the high rate of relapse. However, the neuronal pathways governing
      relapse remain unclear. Using a pathway-specific chemogenetic approach, we found
      that BDNF differentially regulates two key prelimbic pathways to guide long-term
      relapse. Infusion of BDNF in the prelimbic cortex during early withdrawal from
      cocaine self-administration decreases relapse that is prevented when neurons
      projecting from the prelimbic cortex to the nucleus accumbens core are inhibited.
      In contrast, BDNF restores relapse when neurons projecting from the prelimbic
      cortex to the posterior paraventricular thalamic nucleus are inhibited. This
      study demonstrates that two divergent cortical outputs mediate relapse that is
      regulated in opposite directions by infusing BDNF in the prelimbic cortex during
      early withdrawal from cocaine.

PMID- 30185463
TI  - Attractor-like Dynamics in Belief Updating in Schizophrenia.
AB  - Subjects with a diagnosis of schizophrenia (Scz) overweight unexpected evidence
      in probabilistic inference: such evidence becomes "aberrantly salient." A
      neurobiological explanation for this effect is that diminished synaptic gain
      (e.g., hypofunction of cortical NMDARs) in Scz destabilizes quasi-stable neuronal
      network states (or "attractors"). This attractor instability account predicts
      that (1) Scz would overweight unexpected evidence but underweight consistent
      evidence, (2) belief updating would be more vulnerable to stochastic fluctuations
      in neural activity, and (3) these effects would correlate. Hierarchical Bayesian
      belief updating models were tested in two independent datasets (n = 80 male and n
      = 167 female) comprising human subjects with Scz, and both clinical and
      nonclinical controls (some tested when unwell and on recovery) performing the
      "probability estimates" version of the beads task (a probabilistic inference
      task). Models with a standard learning rate, or including a parameter increasing
      updating to "disconfirmatory evidence," or a parameter encoding belief
      instability were formally compared. The "belief instability" model (based on the
      principles of attractor dynamics) had most evidence in all groups in both
      datasets. Two of four parameters differed between Scz and nonclinical controls in
      each dataset: belief instability and response stochasticity. These parameters
      correlated in both datasets. Furthermore, the clinical controls showed similar
      parameter distributions to Scz when unwell, but were no different from controls
      once recovered. These findings are consistent with the hypothesis that attractor
      network instability contributes to belief updating abnormalities in Scz, and
      suggest that similar changes may exist during acute illness in other psychiatric
      conditions.SIGNIFICANCE STATEMENT Subjects with a diagnosis of schizophrenia
      (Scz) make large adjustments to their beliefs following unexpected evidence, but
      also smaller adjustments than controls following consistent evidence. This has
      previously been construed as a bias toward "disconfirmatory" information, but a
      more mechanistic explanation may be that in Scz, neural firing patterns
      ("attractor states") are less stable and hence easily altered in response to both
      new evidence and stochastic neural firing. We model belief updating in Scz and
      controls in two independent datasets using a hierarchical Bayesian model, and
      show that all subjects are best fit by a model containing a belief instability
      parameter. Both this and a response stochasticity parameter are consistently
      altered in Scz, as the unstable attractor hypothesis predicts.

PMID- 30185464
TI  - Sleep Strengthens Predictive Sequence Coding.
AB  - Predictive-coding theories assume that perception and action are based on
      internal models derived from previous experience. Such internal models require
      selection and consolidation to be stored over time. Sleep is known to support
      memory consolidation. We hypothesized that sleep supports both consolidation and
      abstraction of an internal task model that is subsequently used to predict
      upcoming stimuli. Human subjects (of either sex) were trained on deterministic
      visual sequences and tested with interleaved deviant stimuli after retention
      intervals of sleep or wakefulness. Adopting a predictive-coding approach, we
      found increased prediction strength after sleep, as expressed by increased error
      rates to deviant stimuli, but fewer errors for the immediately following standard
      stimuli. Sleep likewise enhanced the formation of an abstract sequence model,
      independent of the temporal context during training. Moreover, sleep increased
      confidence for sequence knowledge, reflecting enhanced metacognitive access to
      the model. Our results suggest that sleep supports the formation of internal
      models which can be used to predict upcoming events in different
      contexts.SIGNIFICANCE STATEMENT To efficiently interact with the ever-changing
      world, we predict upcoming events based on similar previous experiences. Sleep is
      known to benefit memory consolidation. However, it is not clear whether sleep
      specifically supports the transformation of past experience into predictions of
      future events. Here, we find that, when human subjects sleep after learning a
      sequence of predictable visual events, they make better predictions about
      upcoming events compared with subjects who stayed awake for an equivalent period
      of time. In addition, sleep supports the transfer of such knowledge between
      different temporal contexts (i.e., when sequences unfold at different speeds).
      Thus, sleep supports perception and action by enhancing the predictive utility of
      previous experiences.

PMID- 30185461
TI  - Graded Transmission without Action Potentials Sustains Rhythmic Activity in Some
      But Not All Modulators That Activate the Same Current.
AB  - Neurons in the central pattern-generating circuits in the crustacean
      stomatogastric ganglion (STG) release neurotransmitter both as a graded function
      of presynaptic membrane potential that persists in TTX and in response to action
      potentials. In the STG of the male crab Cancer borealis, the modulators
      oxotremorine, C. borealis tachykinin-related peptide Ia (CabTRP1a), red pigment
      concentrating hormone (RPCH), proctolin, TNRNFLRFamide, and crustacean
      cardioactive peptide (CCAP) produce and sustain robust pyloric rhythms by
      activating the same modulatory current (I MI), albeit on different subsets of
      pyloric network targets. The muscarinic agonist oxotremorine, and the peptides
      CabTRP1a and RPCH elicited rhythmic triphasic intracellular alternating
      fluctuations of activity in the presence of TTX. Intracellular waveforms of
      pyloric neurons in oxotremorine and CabTRP1a in TTX were similar to those in the
      intact rhythm, and phase relationships among neurons were conserved. Although
      cycle frequency was conserved in oxotremorine and TTX, it was altered in CabTRP1a
      in the presence of TTX. Both rhythms were primarily driven by the pacemaker
      kernel consisting of the Anterior Burster and Pyloric Dilator neurons. In
      contrast, in TTX the circuit remained silent in proctolin, TNRNFLRFamide, and
      CCAP. These experiments show that graded synaptic transmission in the absence of
      voltage-gated Na+ current is sufficient to sustain rhythmic motor activity in
      some, but not other, modulatory conditions, even when each modulator activates
      the same ionic current. This further demonstrates that similar rhythmic motor
      patterns can be produced by qualitatively different mechanisms, one that depends
      on the activity of voltage-gated Na+ channels, and one that can persist in their
      absence.SIGNIFICANCE STATEMENT The pyloric rhythm of the crab stomatogastric
      ganglion depends both on spike-mediated and graded synaptic transmission. We
      activate the pyloric rhythm with a wide variety of different neuromodulators, all
      of which converge on the same voltage-dependent inward current. Interestingly,
      when action potentials and spike-mediated transmission are blocked using TTX, we
      find that the muscarinic agonist oxotremorine and the neuropeptide CabTRP1a
      sustain rhythmic alternations and appropriate phases of activity in the absence
      of action potentials. In contrast, TTX blocks rhythmic activity in the presence
      of other modulators. This demonstrates fundamental differences in the burst
      generation mechanisms in different modulators that would not be suspected on the
      basis of their cellular actions at the level of the targeted current.

PMID- 30185465
TI  - TOM1 Regulates Neuronal Accumulation of Amyloid-beta Oligomers by FcgammaRIIb2
      Variant in Alzheimer's Disease.
AB  - Emerging evidences suggest that intraneuronal Abeta correlates with the onset of
      Alzheimer's disease (AD) and highly contributes to neurodegeneration. However,
      critical mediator responsible for Abeta uptake in AD pathology needs to be
      clarified. Here, we report that FcgammaRIIb2, a variant of Fcgamma-receptor IIb
      (FcgammaRIIb), functions in neuronal uptake of pathogenic Abeta. Cellular
      accumulation of oligomeric Abeta1-42, not monomeric Abeta1-42 or oligomeric
      Abeta1-40, was blocked by Fcgr2b knock-out in neurons and partially in
      astrocytes. Abeta1-42 internalization was FcgammaRIIb2 di-leucine motif-dependent
      and attenuated by TOM1, a FcgammaRIIb2-binding protein that repressed the
      receptor recycling. TOM1 expression was downregulated in the hippocampus of male
      3xTg-AD mice and AD patients, and regulated by miR-126-3p in neuronal cells after
      exposure to Abeta1-42 In addition, memory impairments in male 3xTg-AD mice were
      rescued by the lentiviral administration of TOM1 gene. Augmented Abeta uptake
      into lysosome caused its accumulation in cytoplasm and mitochondria. Moreover,
      neuronal accumulation of Abeta in both sexes of 3xTg-AD mice and memory deficits
      in male 3xTg-AD mice were ameliorated by forebrain-specific expression of Abeta
      uptake-defective Fcgr2b mutant. Our findings suggest that FcgammaRIIb2 is
      essential for neuropathic uptake of Abeta in AD.SIGNIFICANCE STATEMENT
      Accumulating evidences suggest that intraneuronal Abeta is found in the early
      step of AD brain and is implicated in the pathogenesis of AD. However, the
      critical mediator involved in these processes is uncertain. Here, we describe
      that the FcgammaRIIb2 variant is responsible for both neuronal uptake and
      intraneuronal distribution of pathogenic Abeta linked to memory deficits in AD
      mice, showing a pathologic significance of the internalized Abeta. Further, Abeta
      internalization is attenuated by TOM1, a novel FcgammaRIIb2-binding protein.
      Together, we provide a molecular mechanism responsible for neuronal uptake of
      pathogenic Abeta found in AD.

PMID- 30185462
TI  - Hippocampal-Evoked Feedforward Inhibition in the Nucleus Accumbens.
AB  - The nucleus accumbens (NAc) is critical for motivated behavior and is rewired
      following exposure to drugs of abuse. Medium spiny neurons (MSNs) in the NAc
      express either D1 or D2 receptors and project to distinct downstream targets.
      Differential activation of these MSNs depends on both excitation from long-range
      inputs and inhibition via the local circuit. Assessing how long-range excitatory
      inputs engage inhibitory circuitry is therefore important for understanding NAc
      function. Here, we use slice electrophysiology and optogenetics to study ventral
      hippocampal (vHPC)-evoked feedforward inhibition in the NAc of male and female
      mice. We find that vHPC-evoked excitation is stronger at D1+ than D1- MSNs,
      whereas inhibition is unbiased at the two cell types. vHPC inputs contact both
      parvalbumin-positive (PV+) and somatostatin-positive (SOM+) interneurons, but PV+
      cells are preferentially activated. Moreover, suppressing PV+ interneurons
      indicates they are primarily responsible for vHPC-evoked inhibition. Finally,
      repeated cocaine exposure alters the excitation of D1+ and D1- MSNs, without
      concomitant changes to inhibition, shifting the excitation/inhibition balance.
      Together, our results highlight the contributions of multiple interneuron
      populations to feedforward inhibition in the NAc. Moreover, they demonstrate that
      inhibition provides a stable backdrop on which drug-evoked changes to excitation
      occur within this circuit.SIGNIFICANCE STATEMENT Given the importance of the
      nucleus accumbens (NAc) in reward learning and drug-seeking behaviors, it is
      critical to understand what controls the activity of cells in this region. While
      excitatory inputs to projection neurons in the NAc have been identified, it is
      unclear how the local inhibitory network becomes engaged. Here, we identify a
      sparse population of interneurons responsible for feedforward inhibition evoked
      by ventral hippocampal input and characterize their connections within the NAc.
      We also demonstrate that the balance of excitation and inhibition that projection
      neurons experience is altered by exposure to cocaine. Together, this work
      provides insight into the fundamental circuitry of this region as well as the
      effects of drugs of abuse.

PMID- 30185467
TI  - In-Center Hemodialysis: Time for a Paradigm Shift.

PMID- 30185466
TI  - Reduced Microglial Activity and Enhanced Glutamate Transmission in the
      Basolateral Amygdala in Early CNS Autoimmunity.
AB  - Emotional dysfunction is common in multiple sclerosis (MS) patients and in mouse
      models of MS, including experimental autoimmune encephalomyelitis (EAE); however,
      the etiology of these behaviors is poorly understood. To identify CNS changes
      associated with these behaviors, we focused on the basolateral amygdala (BLA)
      because of its central role in the regulation of emotional behavior. Whole-cell
      recordings were performed in the principal neurons of the BLA in early EAE,
      before demyelination, T-cell invasion, and motor dysfunction. EAE female mice
      displayed increased frequency of mEPSCs, with no alteration in amplitude or
      evoked EPSC paired-pulse ratio compared with controls. We found an increase in
      the AMPA-NMDA ratio and dendritic spine density, indicating increased numbers of
      glutamatergic synapses. We saw similar electrophysiological changes in BLA
      principal neurons after microglia were either inactivated (minocycline) or
      depleted (Mac1-Saporin) in the BLA. Microglia regulate synapses through pruning,
      directed by complement protein 3 (C3) expression. C3 was downregulated in the BLA
      in EAE. Ultrastructural analysis of microglia revealed more complex ramifications
      and reduced extracellular digestion of cellular elements. We also observed
      reduced IBA-1 and CD68 staining and lack of proinflammatory cytokine expression
      in the amygdala. Thus, early EAE is a state of microglial "deactivation"
      associated with reduced synaptic pruning. This contrasts with the prototypic
      microglial activation commonly associated with inflammatory CNS disease.
      Additionally, these data support a role for the acquired immune system to
      influence both neuronal and microglial function in early CNS
      autoimmunity.SIGNIFICANCE STATEMENT Microglia help regulate synaptic homeostasis,
      but there has been little evidence for how this might be important in
      neuroinflammatory diseases. The data from this study reveal increased synaptic
      activity and spine density in early stages of experimental autoimmune
      encephalomyelitis (an animal model of multiple sclerosis) in the basolateral
      amygdala, a nucleus important in the types of behavioral changes we have
      previously described. These electrophysiological and morphological effects
      occurred without significant elevation of local inflammatory cytokines or local
      demyelination. Unexpectedly, in the context of inflammatory state, we found that
      microglia were "deactivated." This study provides strong evidence for a link
      between microglial activity and synaptic function; the conclusions contrast with
      the generally accepted view that microglia are activated in inflammatory disease.

PMID- 30185470
TI  - Perspective: Will We Ever Know the Optimal Hgb Level in ESRD?

PMID- 30185468
TI  - Human-Specific Abnormal Alternative Splicing of Wild-Type PKD1 Induces Premature
      Termination of Polycystin-1.
AB  - BACKGROUND: The major form of autosomal dominant polycystic kidney disease is
      caused by heterozygous mutations in PKD1, the gene that encodes polycystin-1
      (PC1). Unlike PKD1 genes in the mouse and most other mammals, human PKD1 is
      unusual in that it contains two long polypyrimidine tracts in introns 21 and 22
      (2.5 kbp and 602 bp, respectively; 97% cytosine and thymine). Although these
      polypyrimidine tracts have been shown to form thermodynamically stable segments
      of triplex DNA that can cause DNA polymerase stalling and enhance the local
      mutation rate, the efficiency of transcription and splicing across these cytosine
      and thymine-rich introns has been unexplored. METHODS: We used RT-PCR and
      Western blotting (using an mAb to the N terminus) to probe splicing events over
      exons 20-24 in the mouse and human PKD1 genes as well as Nanopore sequencing to
      confirm the presence of multiple splice forms. RESULTS: Analysis of PC1 indicates
      that humans, but not mice, have a smaller than expected protein product, which we
      call Trunc_PC1. The findings show that Trunc_PC1 is the protein product of
      abnormal differential splicing across introns 21 and 22 and that 28.8%-61.5% of
      PKD1 transcripts terminate early. CONCLUSIONS: The presence of polypyrimidine
      tracts decreases levels of full-length PKD1 mRNA from normal alleles. In
      heterozygous individuals, low levels of full-length PC1 may reduce polycystin
      signaling below a critical "cystogenic" threshold.

PMID- 30185471
TI  - Treatment of experimentally induced bovine respiratory disease in young calves
      with a single administration of a combination of florfenicol and meloxicam.
AB  - This study was designed to evaluate the efficacy of a new florfenicol/meloxicam
      combination (FMC) in calves with bovine respiratory disease. A total of 90 young
      calves were challenged via intratracheal deposition of 108 colony-forming units
      of Mannheimia haemolytica Data for 84 calves demonstrating a rectal temperature
      (RT) above 39.5 degrees C and a combined total clinical score (TCS) greater than
      or equal to 3 were included. Calves were then randomly allocated to one of the
      three study groups (FMC; florfenicol/flunixin combination (FFC); or saline) and
      promptly treated. RT and TCS of calves treated with an FMC or FFC were
      consistently lower than RT and TCS of calves belonging to the control group
      (P<0.001). Moreover, at the end of the study, a high clinical cure rate was
      observed in calves treated with FMC (100 per cent) or FFC (96.6 per cent) whereas
      cure was limited for calves receiving saline (29.6 per cent). Interestingly,
      calves treated with FMC were cured without relapse more rapidly compared with
      calves treated with FFC (HR=1.76, P<0.05) and with a lower percentage of clinical
      relapse due to fever (P=0.05). These results underline the high efficacy of the
      FMC and are in line with the pharmacokinetic properties of florfenicol and
      meloxicam.

PMID- 30185472
TI  - Pet owners' perceptions of veterinary safety practices.
AB  - Veterinary workers must care for their animal patients while simultaneously
      protecting their own health and safety. This process can be complicated by the
      presence and perception of pet owners who may not agree with a given tactic used
      to protect veterinary workers from injury. We conducted focus groups of pet
      owners in the Seattle area during November 2016 to gain a deeper understanding of
      their perceptions relating to veterinary worker safety practices. Focus group
      interviews were recorded and transcribed and study themes identified and
      summarised. Twenty pet owners participated in three focus groups. Study themes
      arising from the focus group discussions could be categorised into human, animal,
      behavioural and environmental domains as outlined in a One Health Occupational
      Safety and Health (OHOSH) model. Communication was a recurring study theme
      identified, suggesting that lacking or impaired veterinary personnel-client
      communication plays a key role in the safe delivery of veterinary services and
      can negatively impact the use of safety practices among veterinary personnel. Our
      study suggests that it is important for veterinary personnel to communicate to
      clients the reasons for policies related to worker safety. Such communication can
      help engage the veterinary client in order to effectively avoid situations that
      precipitate injury.

PMID- 30185473
TI  - Pancreatitis: summary of NICE guidance.

PMID- 30185469
TI  - The Absence of the ACE N-Domain Decreases Renal Inflammation and Facilitates
      Sodium Excretion during Diabetic Kidney Disease.
AB  - BACKGROUND: Recent evidence emphasizes the critical role of inflammation in the
      development of diabetic nephropathy. Angiotensin-converting enzyme (ACE) plays an
      active role in regulating the renal inflammatory response associated with
      diabetes. Studies have also shown that ACE has roles in inflammation and the
      immune response that are independent of angiotensin II. ACE's two catalytically
      independent domains, the N- and C-domains, can process a variety of substrates
      other than angiotensin I. METHODS: To examine the relative contributions of each
      ACE domain to the sodium retentive state, renal inflammation, and renal injury
      associated with diabetic kidney disease, we used streptozotocin to induce
      diabetes in wild-type mice and in genetic mouse models lacking either a
      functional ACE N-domain (NKO mice) or C-domain (CKO mice). RESULTS: In response
      to a saline challenge, diabetic NKO mice excreted 32% more urinary sodium
      compared with diabetic wild-type or CKO mice. Diabetic NKO mice also exhibited
      55% less renal epithelial sodium channel cleavage (a marker of channel activity),
      55% less renal IL-1beta, 53% less renal TNF-alpha, and 53% less albuminuria than
      diabetic wild-type mice. This protective phenotype was not associated with
      changes in renal angiotensin II levels. Further, we present evidence that the
      anti-inflammatory tetrapeptide N-acetyl-seryl-asparyl-lysyl-proline (AcSDKP), an
      ACE N-domain-specific substrate that accumulates in the urine of NKO mice,
      mediates the beneficial effects observed in the NKO. CONCLUSIONS: These data
      indicate that increasing AcSDKP by blocking the ACE N-domain facilitates sodium
      excretion and ameliorates diabetic kidney disease independent of intrarenal
      angiotensin II regulation.

PMID- 30185474
TI  - Primary prevention with statins for older adults.

PMID- 30185475
TI  - NHS England's "hierarchy of goals" can be used to argue for service expansion.

PMID- 30185476
TI  - Starting Dialysis-Planning for the Unpredictable and the Search for Meaningful
      Process Measures.

PMID- 30185477
TI  - Early Peritoneal Dialysis Technique Failure: Review.
AB  - There is a growing, global burden of patients with end-stage kidney disease
      (ESKD) requiring renal replacement therapy. Although peritoneal dialysis (PD) is
      considered to be the most cost-effective dialysis modality, its utilization has
      been declining in some regions. The first year after starting PD is thought to be
      a vulnerable period for technique failure, which in turn contributes to poor
      patient retention. Improved understanding of the risk factors for technique
      failure during this period may help the development of targeted strategies to
      lower its incidence and improve both the utilization and utility of PD. This up
      to-date review will summarize current evidence regarding the definition,
      incidence, causes, and predictors of early PD technique failure. Promising
      avenues for directing future research efforts will also be discussed.

PMID- 30185478
TI  - Sustained Increase in Peritoneal Dialysis Prevalence through a Structured PD
      Initiation Service.
AB  - A structured peritoneal dialysis (PD) initiation service provided by a dedicated
      team of nephrologists, interventionists, and PD nurses, taking patients through
      the stages of predialysis education and monitoring, dialysis catheter insertion,
      dialysis initiation, and follow-up in the immediate post-dialysis initiation
      period, can go a long way in expanding PD prevalence. The authors noticed a rapid
      expansion of their PD program following the introduction of such a service, and
      they share their experience in this article. A multidisciplinary team providing 1
      stop coordinated care may help in alleviating the differences in patient
      selection criteria, minimize delays in PD catheter insertions, ensure timely
      initiation of dialysis, reduce the need to start dialysis urgently, actively
      identify and sort any teething issues, enhance patients' confidence, and reduce
      technique failures.

PMID- 30185479
TI  - Case Study: Applying Rapid Flow Cytometry Analysis to CAPD Effluent.
AB  - Peritoneal dialysis (PD) peritonitis cases require rapid clinical interventions
      to ensure the best possible patient outcomes. Culture-dependent microbiology
      tools are slow and cannot provide clinicians with evidence to guide antimicrobial
      prescription practices in an appropriate time frame. Genotypic methods have met
      with limited success for analyzing continuous ambulatory PD effluent, with most
      centers still relying on culture-dependent microbiology. We present a case study
      in which we apply flow cytometry techniques to antibiotic-compromised effluent.
      We demonstrate, with supporting evidence, direct enumeration of bacterial and
      human immune cells, with results reported within 2 hours of receiving the
      clinical specimen.

PMID- 30185480
TI  - Successful Treatment of PD Peritonitis Due to Brevundimonas vesicularis.
AB  - Brevundimonas vesicularis is a rare cause of peritoneal dialysis-associated
      peritonitis (PD peritonitis). One documented case report described poor outcome
      despite treatment with appropriate antibiotics. Here, we report the successful
      treatment of PD peritonitis due to Brevundimonas vesicularis with 21 days of
      intraperitoneal (IP) antibiotics using the regimen described for Pseudomonas
      aeruginosa, notably IP gentamicin (10 days) followed by IP cefepime and oral
      ciprofloxacin (11 days). Despite the favorable outcome, measurement of antibiotic
      concentrations in the PD effluent suggests that the cefepime and possibly
      ciprofloxacin regimens do not achieve key antibiotic concentration targets that
      are reported to maximize bacterial kill. The role of routine therapeutic drug
      monitoring to maximize clinical outcomes from antibiotic therapy for PD
      peritonitis requires further consideration.

PMID- 30185481
TI  - Systemic Endotoxin in Peritoneal Dialysis Patients.
AB  - Previous reports linked systemic endotoxemia in dialysis patients to increased
      markers of inflammation, cardiovascular disease, and mortality. Many peritoneal
      dialysis (PD) patients use acidic, hypertonic dialysates, which could potentially
      increase gut permeability, resulting in systemic endotoxemia. However, the
      results from studies measuring endotoxin in PD patients are discordant. We
      therefore measured systemic endotoxin in 55 PD outpatients attending for routine
      assessment of peritoneal membrane function; mean age 58.7 +/- 16.4 years, 32
      (58.2%) male, 21 (38.2%) diabetic, median duration of PD treatment 19.5 (13 - 31)
      months, 32 (58.2%) using 22.7 g/L dextrose dialysates, and 47 (85.5%) icodextrin.
      The median systemic endotoxin concentration was 0.0485 (0.0043 - 0.103) Eu/mL. We
      found no association between endotoxin levels and patient demographics, markers
      of inflammation, serum albumin, N-terminal pro-brain natriuretic peptide,
      extracellular volume measured by bioimpedance, blood pressure, PD prescriptions
      or peritoneal membrane transporter status, or medications. The measurement of
      endotoxin can be lowered by failure to effectively release protein-bound
      endotoxin prior to analysis and increased by contamination when taking blood
      samples and processing and storing the samples. Additionally, contamination with
      beta-glucan from fungal cell walls and the use of different assays to analyze
      endotoxin can also give differing results. These factors may help to explain the
      disparate results reported in different studies. Our study would suggest that
      exposure to standard peritoneal dialysates does not substantially increase
      systemic endotoxin. However, until endotoxin assays can measure free and bound
      endotoxin separately, the role of endotoxin causing inflammation in PD patients
      remains to be determined.

PMID- 30185482
TI  - Estimating Dietary Protein Intake in Peritoneal Dialysis Patients: The Effect of
      Ethnicity.
AB  - Kidney dialysis patients with sarcopenia have increased mortality. Clinical
      guidelines recommend peritoneal dialysis (PD) patients have a target daily
      protein intake to prevent sarcopenia. Protein intake is estimated from total
      daily urea losses in urine and peritoneal dialysate to assess the protein
      equivalent of nitrogen appearance rate adjusted for body weight (nPNA). Dietary
      habits differ among ethnic groups, so we reviewed nPNA and body composition in a
      multi-ethnic PD population. Body composition was measured with multifrequency
      bioimpedance in 598 patients (301 white, 136 black, 123 South-Asian, and 38 Asian
      Pacific). South-Asians had a lower nPNA compared with white and black individuals
      (Randerson 0.80 +/- 0.21 vs 0.88 +/- 0.24 and 0.85 +/- 0.24 g/kg/day,
      Blumenkrantz 0.97 +/- 0.14 vs 1.04 +/- 0.22 and 0.99 +/- 0.22 g/kg/day, Bergstrom
      0.87 +/- 0.4 vs 0.95 +/- 0.24 and 0.92 +/- 0.24 g/kg/day all p < 0.001). South
      Asians had lower weights (68.9 +/- 14.9 vs 74.4 +/- 16.6 and 73.5 +/- 16.3 kg, p
      < 0.001), and although of similar body mass index (25.9 +/- 4.9 vs 28.5 +/- 4.9
      and 26.5 +/- 5.2 kg/m2), had both lower skeletal muscle and appendicular muscle
      mass indexed for height (9.08 +/- 1.45 vs 9.89 +/- 1.62 and 10.1 +/- 1.85, p <
      0.001; and 6.95 +/- 1.39 vs 7.68 +/- 1.48 and 7.67 +/- 1.58 kg/m2p < 0.01). South
      Asian patients had a lower calculated basal metabolic rate (BMR) (1,358 +/- 218
      vs 1,487 +/- 257 and 1,489 +/- 271 kcal/day, p < 0.001).Asian PD patients,
      particularly South-Asians, have lower dietary protein intakes when calculated by
      nPNA. However, South-Asians had lower measured muscle mass and calculated BMR. As
      such, dietary protein intake targets derived from studies in 1 ethnic group are
      not necessarily applicable for all patients, as those with less muscle mass and
      lower BMR may well need less daily protein intake to maintain homeostasis.

PMID- 30185484
TI  - A Plea for Revitalizing Interest in Pharmacodynamics in the Light of Emerging
      Bacterial Resistance and Its Prevention.

PMID- 30185485
TI  - Infected Thoracoabdominal Aneurysm and Peritonitis in Peritoneal Dialysis
      Patient.

PMID- 30185483
TI  - Characteristics and Outcomes of Exit Sites of Buried Peritoneal Dialysis
      Catheters: A Cohort Study.
AB  - Buried peritoneal dialysis (PD) catheters are placed months before dialysis is
      needed and the exit site is created when the catheter is dissected out at the
      initiation of dialysis. In contrast, the exit site of an unburied catheter is
      created by the surgeon at the time of insertion. We reviewed all patients who
      initiated PD at our center over a 2-year period. At each clinic visit, exit sites
      were subjectively classified into standard predefined groups. Outcomes of
      interest were the frequency of perfect exit sites at 2, 6, and 12 months and rate
      of exit-site infections (ESIs) at 90 days. One hundred and seventy-seven patients
      initiated PD during the period of interest, and 169, 157, and 144 remained on PD
      at 2, 6, and 12 months, respectively. Ninety-three patients had buried catheters,
      and 76 patients had unburied catheters. Both groups had similar frequency of
      perfect appearance of exit sites at 2, 6, and 12 months (37/93 vs 41/76 at 2
      months; 54/87 vs 43/70 at 6 months; 50/ 81 vs 35/ 63 at 12 months in buried and
      unburied groups, respectively). More patients with buried catheters had ESIs in
      the first 3 months (7/93 vs 1/76, p = 0.059). We conclude that exit sites of
      buried PD catheters do not differ qualitatively from those of unburied catheters.
      The trend towards more ESIs with buried catheters suggests that there may be
      clinical consequences of the tissue trauma at time of exteriorization.

PMID- 30185487
TI  - After a near decade's wait, patient appeals for a heart donor.

PMID- 30185486
TI  - Candida glabrata PD-Associated Peritonitis: A Case Report.

PMID- 30185488
TI  - Acute Decompensated Heart Failure: A Pharmacotherapy Approach.

PMID- 30185489
TI  - From Apps to mHealth: Informing, Interacting, and Changing Behavior.

PMID- 30185490
TI  - Building Healthier Workplaces by Giving Space for Work-Related Grief.

PMID- 30185491
TI  - Pharmacokinetics and Extracorporeal Membrane Oxygenation in Adults: A Literature
      Review.
AB  - Extracorporeal membrane oxygenation is a rapidly emerging treatment for
      respiratory or cardiac failure and is used as a bridge to recovery, transplant,
      or destination therapy. Adult patients receiving extracorporeal membrane
      oxygenation also receive significant amounts of pharmacotherapy. Although the
      body of literature on extra-corporeal membrane oxygenation in general is
      extensive, only a few publications focus on pharmacokinetic changes related to
      extracorporeal membrane oxygenation in adults. Understanding pharmacokinetics in
      adult patients receiving extracorporeal membrane oxygenation is important to
      correctly select and dose medications in this patient population. This article
      reviews published studies of the effects of extracorporeal membrane oxygenation
      on pharmacokinetics in adults.

PMID- 30185492
TI  - Impact of Coaching on the Nurse-Physician Dynamic.
AB  - BACKGROUND: Limited resources and increased patient care demands have strained
      nurse-physician relationships in our hospital's neurosurgical intensive care
      unit, leading to low morale and adversarial dynamics. Studies exploring benefits
      of coaching interprofessional teamwork demonstrate performance improvements.
      Therefore, a coaching program designed to improve nurse-physician teamwork was
      initiated by the neurosurgery department of the hospital's affiliated university.
      OBJECTIVE: To assess the impact of a coaching program for nurses and physicians
      on workplace performance in a neurosurgical intensive care unit at a level 1
      trauma center. METHODS: A coach was incorporated into everyday activities on the
      neurosurgical unit. After 3 months of observations, specific interdisciplinary
      initiatives were implemented to foster a more positive workplace environment.
      Nurses' perceptions before and after the initiatives were measured and compared
      using appropriate statistical tools. RESULTS: A significant improvement in
      relationships was found in 6 of 7 targeted categories after the program had been
      in place for 5 months. The results were sustained at 1 year. CONCLUSION: A
      coaching program is an effective method of improving nurse-physician
      relationships, leading to enhanced workplace performance.

PMID- 30185493
TI  - Critical Care Obstetrics.

PMID- 30185494
TI  - Physiologic and Hemodynamic Changes During Pregnancy.
AB  - Substantial physiologic changes accompany pregnancy, the most profound of which
      involve the cardiovascular system. These changes affect maternal hemodynamic and
      oxygen transport status. This article describes cardiovascular changes that occur
      during pregnancy including blood volume, heart rate, stroke volume, cardiac
      output, vascular resistance, and colloid osmotic pressure. Alterations in factors
      related to maternal oxygen transport including oxygen affinity, delivery, and
      consumption also are described. Concepts related to fetal oxygen transport and
      adaptive responses to hypoxemia are presented. Technical considerations regarding
      assessment of maternal hemodynamic and oxygen transport status during pregnancy
      are described and assessment findings during labor, birth, and the immediate
      postpartum period are interpreted. A maternal hemodynamic and oxygen transport
      profile is presented to illustrate these principles in clinical practice.

PMID- 30185496
TI  - Cardiac Disease in Pregnancy.
AB  - In the United States, cardiac disease is a leading contributor to maternal
      mortality and morbidity. This review addresses the impact of cardiac disease on
      management of pregnancy and how the physiological changes of pregnancy complicate
      patient treatment. Approaches to assessing risk in pregnant women with cardiac
      disease are reviewed. Key elements of a successful disease management strategy
      are reviewed. Management of cardiac arrest in a pregnant patient is discussed.

PMID- 30185495
TI  - Evidence-Based Strategies for Maternal Stabilization and Rescue in Obstetric
      Hemorrhage.
AB  - Obstetric hemorrhage is one of the most frequent causes of maternal death in the
      United States. More than 70% of maternal deaths from hemorrhage are preventable.
      State and professional quality care organizations have reduced severe maternal
      morbidity by more than 20% by implementing evidence-based guidelines. Successful
      hemorrhage management requires collaborative, multidisciplinary teams of trained
      health care personnel. Hemorrhage management's primary goal is to stop the
      bleeding before the occurrence of maternal hypovolemia, acidosis, coagulopathy,
      and death. Uterine atony is the primary cause of obstetric hemorrhage and can be
      managed with uterotonic agents, placement of noninvasive uterine tamponade
      balloons, and surgical procedures if needed. Women experiencing massive
      hemorrhage should be treated according to resuscitation care guidelines with
      avoidance of hypothermia, acidosis, and coagulopathy. Use of a massive
      transfusion protocol is warranted for best outcomes. Resources for institutional
      adoption of current collaborative standards for managing obstetric hemorrhage are
      identified in this article.

PMID- 30185497
TI  - Recognition and Management of Sepsis in the Obstetric Patient.
AB  - Sepsis is one of the principal causes of maternal mortality in obstetrics.
      Physiologic changes that occur during pregnancy create a vulnerable environment,
      predisposing pregnant patients to the development of sepsis. Furthermore, these
      changes can mask sepsis indicators normally seen in the nonobstetric population,
      making it difficult to recognize and treat sepsis in a timely manner. The use of
      maternal-specific early warning tools for sepsis identification and knowledge of
      appropriate interventions and their effects on the mother and fetus can help
      clinicians obtain the best patient outcomes in acute care settings. This article
      outlines the signs and symptoms of sepsis in obstetric patients and discusses
      treatment options used in critical care settings.

PMID- 30185498
TI  - Preeclampsia: Acute Complications and Management Priorities.
AB  - Acute complications of preeclampsia contribute substantially to maternal and
      fetal morbidity and mortality. The considerable variation in onset, clinical
      presentation, and severity of this hypertensive disease that is unique to
      pregnancy creates challenges in identifying risk factors for clinical
      deterioration. Delivery of the fetus remains the only definitive treatment for
      preeclampsia. Surveillance of signs and symptoms and laboratory parameters
      consistent with progression in severity requires an appreciation of the dynamic
      and progressive nature of the disease. This article provides a comprehensive
      overview of the pathophysiology of preeclampsia, setting the foundation for
      discussion of management priorities for acute complications that pose the
      greatest risks to maternal health.

PMID- 30185499
TI  - Pulmonary Edema in Obstetrics: Essential Facts for Critical Care Nurses.
AB  - Pulmonary edema is an acute pregnancy complication that, if uncorrected, can
      result in increased maternal and fetal morbidity and mortality. Although
      pulmonary edema is relatively rare in the general obstetrics population, pregnant
      patients are at increased risk for pulmonary edema because of the physiologic
      changes of pregnancy. The risk may be exacerbated by certain pregnancy-related
      diseases, such as preeclampsia. Prompt identification and appropriate clinical
      management of pulmonary complications is critical to prevent adverse outcomes in
      pregnant patients. This article reviews the collaborative treatment of pulmonary
      edema in pregnant women with complex critical illnesses.

PMID- 30185500
TI  - Clinical Presentation and Treatment of Amniotic Fluid Embolism.
AB  - Obstetric emergencies often require intensive care intervention. Amniotic fluid
      embolism is a rare, unpredictable, and often catastrophic complication of
      pregnancy that is suspected in a woman who experiences cardiac arrest after a
      cesarean section. The condition occurs in approximately 1 in 40 000 births and
      has an average case-fatality rate of 16%. This complication may result from
      activation of an inflammatory response to fetal tissue in the maternal
      circulation. Risk factors may include maternal age over 35 years and conditions
      in which fluid can exchange between the maternal and fetal circulations. The
      presentation is abrupt, with profound cardiovascular and respiratory compromise,
      encephalopathy, fetal distress, and disseminated intravascular coagulopathy.
      Diagnosis is by exclusion and clinical presentation. Treatment is supportive,
      with a focus on reversal of hypoxia and hypotension, delivery of the fetus, and
      correction of coagulopathy. Staff debriefing and psychological support for the
      woman and family are vital.

PMID- 30185501
TI  - Identifying Risk for Falls in Pediatric Patients.

PMID- 30185502
TI  - Using Health System Data for Improvement Science: Getting Started.

PMID- 30185503
TI  - Applications of Grief and Bereavement Theory for Critical Care Nurses.

PMID- 30185504
TI  - Wellens Syndrome.

PMID- 30185505
TI  - Understanding better how emergency doctors work. Analysis of distribution of time
      and activities of emergency doctors: a systematic review and critical appraisal
      of time and motion studies.
AB  - BACKGROUND: Optimising the efficiency and productivity of senior doctors is
      critical to ED function and delivery of safe patient care. Time and motion
      studies (TMS) can allow quantification of how these doctors spend their working
      time, identify inefficiencies in the current work processes and provide insights
      into improving working conditions, and enhancing productivity. Three questions
      were addressed: (1) How do senior emergency doctors spend their time in the ED?
      (2) How much of their time is spent on multitasking? (3) What is the number of
      tasks completed per hour? METHODS: The literature was systematically searched for
      TMS of senior emergency doctors. We searched for articles published in peer
      reviewed journals in English language from 1998 to 2018 in the following
      databases: MEDLINE, EMBASE, Scopus, Web of Science and Cochrane. Studies were
      assessed for methodological quality using evidence-based quality criteria
      relevant for TMS including duration of observation, observer bias, Hawthorne
      effect and whether the task classification acknowledged any previous existing
      schemes. A narrative synthesis approach was followed. RESULTS: Fourteen TMS were
      included. The studies were liable to several biases including observer and
      Hawthorne bias. Overall, the time spent on direct face-to-face contact with the
      patient accounted for at least around 25%-40% of the senior doctors' time. The
      remaining time was mostly spent on indirect clinical care such as communication
      (8%-44%), documentation (10%-28%) and administrative tasks (2%-20%). The
      proportion of time spent on multitasking ranged from 10% to 23%. When reported,
      the number of tasks performed per hour was generally high. CONCLUSION: The review
      revealed that senior doctors spent a large percentage of their time on direct
      face-to-face contact with patients. The review findings provided a grounded
      understanding of how senior doctors spent their time in the ED and could be
      useful in implementing improvements to the emergency care system.

PMID- 30185506
TI  - TSC1 deletion in fibroblasts alleviates lipopolysaccharide-induced acute kidney
      injury.
AB  - Mechanistic target of rapamycin complex 1 (mTORC1) signaling is active in
      inflammation, but its involvement in septic acute kidney injury (AKI) has not
      been shown. mTORC1 activation (p-S6) in renal fibroblasts was increased in a
      mouse AKI model induced by 1.5 mg/kg lipopolysaccharide (LPS). Deletion of
      tuberous sclerosis complex 1 (TSC1), an mTORC1 negative regulator, in fibroblasts
      (Fibro-TSC1-/-) inhibited the elevation of serum creatinine and blood urea
      nitrogen in AKI compared with that in TSC1fl/fl control mice. Endothelin-1 (EDN1)
      and phospho-Jun-amino-terminal kinase (p-JNK) were up-regulated in Fibro-TSC1-/-
      renal fibroblasts after LPS challenge. Rapamycin, an mTORC1 inhibitor, and
      bosentan, an EDN1 antagonist, eliminated the difference in renal function between
      TSC1fl/fl and Fibro-TSC1-/- mice after LPS injection. Rapamycin restored LPS
      induced up-regulation of EDN1, endothelin converting enzyme-1 (ECE1), and p-JNK
      in TSC1-knockdown mouse embryonic fibroblasts (MEFs). SP600125, a Jun-amino
      terminal kinase (JNK) inhibitor, attenuated LPS-induced enhancement of EDN1 and
      ECE1 in TSC1-knockdown MEFs without a change in phospho-S6 ribosomal protein (p
      S6) level. The results indicate that mTORC1-JNK-dependent up-regulation of ECE1
      elevated EDN1 in TSC1-knockout renal fibroblasts and contributed to improvement
      of renal function in Fibro-TSC1-/- mice with LPS-induced AKI. Renal fibroblast
      mTORC1 plays an important role in septic AKI.

PMID- 30185507
TI  - Exacerbated metabolic changes in skeletal muscle of sickle cell mice submitted to
      an acute ischemia-reperfusion paradigm.
AB  - Sickle cell disease (SCD) is characterized by painful vaso-occlusive crisis.
      While there are several metabolic abnormalities potentially associated with
      muscular ischemia-reperfusion cycles that could be harmful in the context of SCD,
      the metabolic consequences of such events are still unknown. Ten controls (HbAA),
      thirteen heterozygous (HbAS), and ten homozygous (HbSS) SCD mice were submitted
      to a standardized protocol of rest-ischemia-reperfusion of the left leg during
      which adenosine triphosphate, phosphocreatine, and inorganic phosphate
      concentrations as well as intramuscular pH were measured using phosphorous
      magnetic resonance spectroscopy (MRS). Forty-eight hours later, skeletal muscles
      were harvested. Oxidative stress markers were then measured on the tibialis
      anterior. At the end of the ischemic period, HbSS mice had a lower pH value as
      compared with the HbAA and HbAS groups (P<0.01). During the reperfusion period,
      the initial rate of phosphocreatine resynthesis was lower in HbSS mice as
      compared with HbAA (P<0.05) and HbAS (P<0.01) animals. No significant difference
      among groups was observed regarding oxidative stress markers. HbSS mice displayed
      a higher intramuscular acidosis during the ischemic period while their
      mitochondrial function was impaired as compared with their HbAA and HbAS
      counterparts. These metabolic abnormalities could worsen the complications
      related to the pathology of SCD.

PMID- 30185508
TI  - Comparison of Six Sample-to-Answer Influenza A/B and Respiratory Syncytial Virus
      Nucleic Acid Amplification Assays Using Respiratory Specimens from Children.
AB  - The rapid and accurate detection of influenza A virus (FluA), influenza B virus
      (FluB), and respiratory syncytial virus (RSV) improves patient care. Sample-to
      answer (STA) platforms based on nucleic acid amplification and detection of these
      viruses are simple, automated, and accurate. We compared six such platforms for
      the detection of FluA, FluB, and RSV: Cepheid GeneXpert Xpress Flu/RSV (Xpert),
      Hologic Panther Fusion Flu A/B/RSV (Fusion), Cobas influenza A/B & RSV (Liat),
      Luminex Aries Flu A/B & RSV (Aries), BioFire FilmArray respiratory panel (RP),
      and Diasorin Simplexa Flu A/B & RSV (Simplexa). Nasopharyngeal (NP) swab
      specimens (n = 225) from children previously tested by RP were assessed on these
      platforms. The results were compared to those of the Centers for Disease Control
      and Prevention (CDC)-developed real-time reverse transcription-PCR (rRT-PCR)
      assay for influenza A/B viruses and RSV. Subtyping for FluA and FluB was
      performed for discrepant analysis where applicable. The percent
      sensitivities/specificities for FluA detection were 100/100 (Fusion), 98.6/99.3
      (Xpert), 100/100 (Liat), 98.6/100 (Aries), 98.6/100 (Simplexa), and 100/100 (RP).
      The percent sensitivities/specificities for FluB detection were 100/100 (Fusion),
      97.9/99.4 (Xpert), 97.9/98.3 (Liat), 93.7/99.4 (Aries), 85.4/99.4 (Simplexa), and
      95.8/97.7 (RP); and those for RSV detection were 98.1/99.4 (Xpert), 98.1/99.4
      (Liat), 96.3/100 (Fusion), 94.4/100 (Aries), 87/94.4 (Simplexa), and 94.4/100
      (RP). The 75 strains confirmed to be FluA included 29 pH1N1, 39 H3N2, 4 sH1N1,
      and 3 untyped strains. The 48 strains confirmed to be FluB included 33 strains of
      the Yamagata lineage, 13 of the Victoria lineage, 1 of both the Yamagata and
      Victoria lineages, and 1 of an unknown lineage. All six STA platforms
      demonstrated >95% sensitivity for FluA detection, while three platforms (Fusion,
      Xpert, and Liat) demonstrated >95% sensitivity for FluB and RSV detection.

PMID- 30185509
TI  - Serological Diagnostics of Lyme Borreliosis: Comparison of Universal and Borrelia
      Species-Specific Tests Based on Whole-Cell and Recombinant Antigens.
AB  - The study compares diagnostic parameters of different commercial serological kits
      based on three different antigen types and correlates test results with the
      status of the patient's Borrelia infection. In total, 8 IgM and 8 IgG kits were
      tested, as follows: enzyme-linked immunosorbent assay (ELISA) (Euroimmun) based
      on whole-cell antigen, 3 species-specific enzyme immunoassays (EIAs) (TestLine),
      Liaison chemiluminescence (DiaSorin), ELISA-Viditest (Vidia), EIA, and Blot-Line
      (TestLine) using recombinant antigens. All tests were performed on a panel of 90
      samples from patients with clinically characterized borreliosis (53 with
      neuroborreliosis, 32 with erythema migrans, and 5 with arthritis) plus 70
      controls from blood donors and syphilis patients. ELISA based on whole-cell
      antigens has superior sensitivity and superior negative predictive value and
      serves as an excellent screening test, although its specificity and positive
      predictive values are low. Species-specific tests have volatile parameters. Their
      low sensitivity and low negative predictive value handicap them in routine
      diagnostics. Tests with recombinant antigens are characterized by high
      specificity and high positive predictive value and have a wide range of use in
      diagnostic practice. Diagnostic parameters of individual tests depend on the
      composition of the sample panel. Only a small proportion of contradictory samples
      giving both negative and positive results is responsible for discrepancies
      between test results. Correlation of test results with the patient's clinical
      state is limited, especially in the erythema migrans group with high proportions
      of negative and contradictory results. In contrast, IgG test results in the
      neuroborreliosis group, which are more concordant, show acceptable agreement with
      Borrelia status.

PMID- 30185510
TI  - Evaluation of the New Multiplex Immunochromatographic O.K.N.V. K-SeT Assay for
      Rapid Detection of OXA-48-like, KPC, NDM, and VIM Carbapenemases.

PMID- 30185511
TI  - Biographical Feature: Ellen Jo Baron, M.S., Ph.D.

PMID- 30185512
TI  - TaxAss: Leveraging a Custom Freshwater Database Achieves Fine-Scale Taxonomic
      Resolution.
AB  - Taxonomy assignment of freshwater microbial communities is limited by the
      minimally curated phylogenies used for large taxonomy databases. Here we
      introduce TaxAss, a taxonomy assignment workflow that classifies 16S rRNA gene
      amplicon data using two taxonomy reference databases: a large comprehensive
      database and a small ecosystem-specific database rigorously curated by scientists
      within a field. We applied TaxAss to five different freshwater data sets using
      the comprehensive SILVA database and the freshwater-specific FreshTrain database.
      TaxAss increased the percentage of the data set classified compared to using only
      SILVA, especially at fine-resolution family to species taxon levels, while across
      the freshwater test data sets classifications increased by as much as 11 to 40%
      of total reads. A similar increase in classifications was not observed in a
      control mouse gut data set, which was not expected to contain freshwater
      bacteria. TaxAss also maintained taxonomic richness compared to using only the
      FreshTrain across all taxon levels from phylum to species. Without TaxAss, most
      organisms not represented in the FreshTrain were unclassified, but at fine taxon
      levels, incorrect classifications became significant. We validated TaxAss using
      simulated amplicon data derived from full-length clone libraries and found that
      96 to 99% of test sequences were correctly classified at fine resolution. TaxAss
      splits a data set's sequences into two groups based on their percent identity to
      reference sequences in the ecosystem-specific database. Sequences with high
      similarity to sequences in the ecosystem-specific database are classified using
      that database, and the others are classified using the comprehensive database.
      TaxAss is free and open source and is available at
      https://www.github.com/McMahonLab/TaxAssIMPORTANCE Microbial communities drive
      ecosystem processes, but microbial community composition analyses using 16S rRNA
      gene amplicon data sets are limited by the lack of fine-resolution taxonomy
      classifications. Coarse taxonomic groupings at the phylum, class, and order
      levels lump ecologically distinct organisms together. To avoid this, many
      researchers define operational taxonomic units (OTUs) based on clustered
      sequences, sequence variants, or unique sequences. These fine-resolution
      groupings are more ecologically relevant, but OTU definitions are data set
      dependent and cannot be compared between data sets. Microbial ecologists studying
      freshwater have curated a small, ecosystem-specific taxonomy database to provide
      consistent and up-to-date terminology. We created TaxAss, a workflow that
      leverages this database to assign taxonomy. We found that TaxAss improves fine
      resolution taxonomic classifications (family, genus, and species). Fine taxonomic
      groupings are more ecologically relevant, so they provide an alternative to OTU
      based analyses that is consistent and comparable between data sets.

PMID- 30185514
TI  - The Transcription Factor VdHapX Controls Iron Homeostasis and Is Crucial for
      Virulence in the Vascular Pathogen Verticillium dahliae.
AB  - Iron homeostasis is essential for full virulence and viability in many pathogenic
      fungi. Here, we showed that the bZip transcription factor VdHapX functions as a
      key regulator of iron homeostasis for adaptation to iron-depleted and iron-excess
      conditions and is required for full virulence in the vascular wilt fungus,
      Verticillium dahliae Deletion of VdHapX impaired mycelial growth and conidiation
      under both iron starvation and iron sufficiency. Furthermore, disruption of
      VdHapX led to decreased formation of the long-lived survival structures of V.
      dahliae, known as microsclerotia. Expression of genes involved in iron
      utilization pathways and siderophore biosynthesis was misregulated in the
      DeltaVdHapX strain under the iron-depleted condition. Additionally, the
      DeltaVdHapX strain exhibited increased sensitivity to high iron concentrations
      and H2O2, indicating that VdHapX also contributes to iron or H2O2 detoxification.
      The DeltaVdHapX strain showed a strong reduction in virulence on smoke tree
      seedlings (Cotinus coggygria) and was delayed in its ability to penetrate plant
      epidermal tissue.IMPORTANCE This study demonstrated that VdHapX is a conserved
      protein that mediates adaptation to iron starvation and excesses, affects
      microsclerotium formation, and is crucial for virulence of V. dahliae.

PMID- 30185515
TI  - MCR-1 Confers Cross-Resistance to Bacitracin, a Widely Used In-Feed Antibiotic.
AB  - Extensive use of colistin in food animals is deemed a major driving force for the
      emergence and transmission of mcr-1 However, a non-colistin usage factor(s)
      contributing to mobile colistin resistance may also exist in animal production
      systems. Given that polymyxin, a bacterium-derived peptide antibiotic, has been
      successfully used as a surrogate to study bacterial resistance to antimicrobial
      peptides (AMPs), acquisition of MCR-1 may confer cross-resistance to the
      unrelated AMPs implicated in practical applications. To test this, we first
      constructed Escherichia coli recombinant strains differing only in the presence
      or absence of functional MCR-1. Among diverse tested AMPs, MCR-1 was observed to
      confer cross-resistance to bacitracin, an in-feed antibiotic widely used in
      animal industry. The significantly (2-fold) increased bacitracin MIC was
      confirmed by using different bacitracin products, broth media, and laboratory
      host strains for susceptibility tests. Subsequently, an original mcr-1 gene
      bearing plasmid, pSLy21, was conjugatively transferred to eight clinical E. coli
      recipient strains isolated from diarrheic pigs, which also led to significantly
      increased MICs of both colistin (4-fold to 8-fold) and bacitracin (2-fold).
      Growth curve examination further demonstrated that MCR-1 provides a growth
      advantage to various E. coli strains in the presence of bacitracin. Given that
      bacitracin, a feed additive displaying low absorption in the intestine, can be
      used in food animals with no withdrawal required, imprudent use of bacitracin in
      food animals may serve as a risk factor to enhance the ecological fitness of MCR
      1-positive E. coli strains, consequently facilitating the persistence and
      transmission of plasmid-mediated colistin resistance in agricultural
      ecosystem.IMPORTANCE Polymyxins (e.g., colistin) are the drugs of last resort to
      treat multidrug-resistant infections in humans. To control mobile colistin
      resistance, there is a worldwide trend to limit colistin use in animal
      production. However, simply limiting colistin use in animal production may still
      not effectively mitigate colistin resistance due to an overlooked non-colistin
      usage factor(s). Using controlled systems, in this study, we observed that MCR-1
      confers cross-resistance to bacitracin, a popular in-feed antibiotic used in food
      animals. Thus, imprudent and extensive usage of bacitracin in food animals may
      serve as a non-colistin usage risk factor for the transmissible colistin
      resistance. Further comprehensive in vitro and in vivo studies are highly
      warranted to generate science-based information for risk assessment and risk
      management of colistin resistance, consequently facilitating the development of
      proactive and effective strategies to mitigate colistin resistance in animal
      production system and protect public health.

PMID- 30185513
TI  - Germinant Synergy Facilitates Clostridium difficile Spore Germination under
      Physiological Conditions.
AB  - Clostridium difficile is a Gram-positive obligate anaerobe that forms spores in
      order to survive for long periods in the unfavorable environment outside a host.
      C. difficile is the leading cause of nosocomial infectious diarrhea worldwide. C.
      difficile infection (CDI) arises after a patient treated with broad-spectrum
      antibiotics ingests infectious spores. The first step in C. difficile
      pathogenesis is the metabolic reactivation of dormant spores within the
      gastrointestinal (GI) tract through a process known as germination. In this work,
      we aim to elucidate the specific conditions and the location within the GI tract
      that facilitate this process. Our data suggest that C. difficile germination
      occurs through a two-step biochemical process that is regulated by pH and bile
      salts, amino acids, and calcium present within the GI tract. Maximal germination
      occurs at a pH ranging from 6.5 to 8.5 in the terminal small intestine prior to
      bile salt and calcium reabsorption by the host. Germination can be initiated by
      lower concentrations of germinants when spores are incubated with a combination
      of bile salts, calcium, and amino acids, and this synergy is dependent on the
      availability of calcium. The synergy described here allows germination to proceed
      in the presence of inhibitory bile salts and at physiological concentrations of
      germinants, effectively decreasing the concentrations of nutrients required to
      initiate an essential step of pathogenesis.IMPORTANCEClostridium difficile is an
      anaerobic spore-forming human pathogen that is the leading cause of nosocomial
      infectious diarrhea worldwide. Germination of infectious spores is the first step
      in the development of a C. difficile infection (CDI) after ingestion and passage
      through the stomach. This study investigates the specific conditions that
      facilitate C. difficile spore germination, including the following: location
      within the gastrointestinal (GI) tract, pH, temperature, and germinant
      concentration. The germinants that have been identified in culture include
      combinations of bile salts and amino acids or bile salts and calcium, but in
      vitro, these function at concentrations that far exceed normal physiological
      ranges normally found in the mammalian GI tract. In this work, we describe and
      quantify a previously unreported synergy observed when bile salts, calcium, and
      amino acids are added together. These germinant cocktails improve germination
      efficiency by decreasing the required concentrations of germinants to
      physiologically relevant levels. Combinations of multiple germinant types are
      also able to overcome the effects of inhibitory bile salts. In addition, we
      propose that the acidic conditions within the GI tract regulate C. difficile
      spore germination and could provide a biological explanation for why patients
      taking proton pump inhibitors are associated with increased risk of developing a
      CDI.

PMID- 30185516
TI  - TLR9 and IL-1R1 Promote Mobilization of Pulmonary Dendritic Cells during
      Beryllium Sensitization.
AB  - Metal-induced hypersensitivity is driven by dendritic cells (DCs) that migrate
      from the site of exposure to the lymph nodes, upregulate costimulatory molecules,
      and initiate metal-specific CD4+ T cell responses. Chronic beryllium disease
      (CBD), a life-threatening metal-induced hypersensitivity, is driven by beryllium
      specific CD4+ Th1 cells that expand in the lung-draining lymph nodes (LDLNs)
      after beryllium exposure (sensitization phase) and are recruited back to the
      lung, where they orchestrate granulomatous lung disease (elicitation phase). To
      understand more about how beryllium exposures impact DC function during
      sensitization, we examined the early events in the lung and LDLNs after pulmonary
      exposure to different physiochemical forms of beryllium. Exposure to soluble or
      crystalline forms of beryllium induced alveolar macrophage death/release of IL
      1alpha and DNA, enhanced migration of CD80hi DCs to the LDLNs, and sensitized HLA
      DP2 transgenic mice after single low-dose exposures, whereas exposures to
      insoluble particulate forms beryllium did not. IL-1alpha and DNA released by
      alveolar macrophages upregulated CD80 on immature BMDC via IL-1R1 and TLR9,
      respectively. Intrapulmonary exposure of mice to IL-1R and TLR9 agonists without
      beryllium was sufficient to drive accumulation of CD80hi DCs in the LDLNs,
      whereas blocking both pathways prevented accumulation of CD80hi DCs in the LDLNs
      of beryllium-exposed mice. Thus, in contrast to particulate forms of beryllium,
      which are poor sensitizers, soluble or crystalline forms of beryllium promote
      death of alveolar macrophages and their release of IL-1alpha and DNA, which act
      as damage-associated molecular pattern molecules to enhance DC function during
      beryllium sensitization.

PMID- 30185517
TI  - Targeting Peroxiredoxin 1 by a Curcumin Analogue, AI-44, Inhibits NLRP3
      Inflammasome Activation and Attenuates Lipopolysaccharide-Induced Sepsis in Mice.
AB  - Aberrant activation of the NLRP3 inflammasome contributes to the onset and
      progression of various inflammatory diseases, making it a highly desirable drug
      target. In this study, we screened a series of small compounds with anti
      inflammatory activities and identified a novel NLRP3 inflammasome inhibitor, AI
      44, a curcumin analogue that selectively inhibited signal 2 but not signal 1 of
      NLRP3 inflammasome activation. We demonstrated that AI-44 bound to peroxiredoxin
      1 (PRDX1) and promoted the interaction of PRDX1 with pro-Caspase-1 (CASP1), which
      led to the suppression of association of pro-CASP1 and ASC. Consequently, the
      assembly of the NLRP3 inflammasome was interrupted, and the activation of CASP1
      was inhibited. Knockdown of PRDX1 significantly abrogated the inhibitory effect
      of AI-44 on the NLRP3 inflammasome. Importantly, AI-44 alleviated LPS-induced
      endotoxemia in mice via suppressing NLRP3 inflammasome activation. Taken
      together, our work highlighted PRDX1 as a negative regulator of NLRP3
      inflammasome activation and suggested AI-44 as a promising candidate compound for
      the treatment of sepsis or other NLRP3 inflammasome-driven diseases.

PMID- 30185518
TI  - Hepatitis B Virus Blocks the CRE/CREB Complex and Prevents TLR9 Transcription and
      Function in Human B Cells.
AB  - Effective B cell responses such as cytokine secretion, proliferation, and Ab
      specific responses are essential to clear hepatitis B virus (HBV) infection.
      However, HBV alters numerous immune pathways to persist in the host. B cell
      activity depends on activation of the innate sensor TLR9 by viral or bacterial
      DNA motifs. How HBV can deregulate B cell functions remains unknown. In this
      study, we show that HBV can enter and decrease TLR9 expression in human primary B
      cells. Using PBMCs from human blood donors, we show that TLR9 expression was
      reduced in all peripheral B cells subsets exposed to HBV. B cell function
      mediated by TLR9, but not TLR7, such as proliferation and proinflammatory
      cytokines secretion, were abrogated in the presence of HBV; however, global Ig
      secretion was not downregulated. Mechanistically, we show, using human myeloma B
      cell line RPMI 8226, that the surface Ag hepatitis B surface Ag was responsible
      for TLR9 dysfunction. hepatitis B surface Ag suppressed the phosphorylation and
      thus the activation of the transcription factor CREB, preventing TLR9 promoter
      activity. Finally, we corroborated our in vitro findings in a cohort of chronic
      HBV carriers and found that TLR9 expression and function were significantly
      suppressed. The effect of HBV on TLR9 activity in B cells gives insights into
      oncoviral immune escape strategies, providing knowledge to develop novel
      immunotherapeutic approaches in chronic HBV-carrier patients.

PMID- 30185519
TI  - C-Type Lectin Receptor CD23 Is Required for Host Defense against Candida albicans
      and Aspergillus fumigatus Infection.
AB  - Infection by invasive fungi, such as Candida albicans, Aspergillus fumigatus, and
      Cryptococcus neoformans, is one of the leading death causes for the increasing
      population of immunocompromised and immunodeficient patients. Several C-type
      lectin receptors (CLRs), including Dectin-1, -2, and -3 and Mincle can recognize
      fungal surface components and initiate the host antifungal immune responses.
      Nevertheless, it remains to be determined whether other CLRs are involved in
      antifungal immunity. Our recent study suggests that CD23 (CLEC4J), a CLR and also
      a well-known B cell surface marker, may function to sense C. albicans components
      in antifungal immunity. However, it is not clear how CD23 functions as a fungal
      pattern recognition receptor and whether the antifungal role of CD23 is specific
      to C. albicans or not. In this study, we show that CD23 can recognize both alpha
      mannan and beta-glucan from the cell wall of C. albicans or A. fumigatus but
      cannot recognize glucuronoxylomannan from Cryptococcus Through forming a complex
      with FcRgamma, CD23 can induce NF-kappaB activation. Consistently, CD23-deficient
      mice were highly susceptible to C. albicans and A. fumigatus but not to C.
      neoformans infection. The expression of CD23 in activated macrophages is critical
      for the activation of NF-kappaB. CD23 deficiency results in impaired expression
      of NF-kappaB-dependent genes, especially iNOS, which induces NO production to
      suppress fungal infection. Together, our studies reveal the CD23-induced
      signaling pathways and their roles in antifungal immunity, specifically for C.
      albicans and A. fumigatus, which provides the molecular basis for designing
      potential therapeutic agents against fungal infection.

PMID- 30185520
TI  - Bronchial Allergen Challenge of Patients with Atopic Asthma Triggers an Alarmin
      (IL-33, TSLP, and IL-25) Response in the Airways Epithelium and Submucosa.
AB  - The alarmin cytokines IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) play
      a critical role in asthma pathogenesis by inducing mucosal Th2-type cytokine
      production. Although environmental exposure to aeroallergens has been proposed as
      an alarmin trigger in asthma, there has been no systematic parallel study of the
      effects of allergen exposure on the expression of these cytokines in the airways
      of human asthmatics. Using single and sequential double immunohistochemistry, we
      evaluated the numbers and phenotypes of IL-25-, IL-33-, and TSLP-immunoreactive
      cells in sections of bronchial biopsies from mild atopic asthmatics (n = 16)
      before and 24 h after allergen inhalational challenge. Allergen challenge highly
      increased expression of baseline immunoreactivity for IL-25, IL-33, and TSLP,
      both in the bronchial epithelium and submucosa (p < 0.001), to a degree that
      correlated with the extent of the late phase of airway obstruction. Aside from
      epithelial cells, the principal source of immunoreactivity for all three
      alarmins, TSLP, and IL-33 immunoreactivity colocalized principally with
      endothelial cells and mast cells, neutrophils, and fibroblasts, whereas IL-25
      immunoreactivity colocalized principally with eosinophils as well as endothelial
      cells, mast cells, and fibroblasts. The data implicate that allergen challenge
      directly increases airway alarmin expression in atopic asthmatics to a degree
      correlating with increase late-phase airway obstruction, affirming these
      molecules as potential molecular targets for the inhibition of allergen-induced
      airway inflammation and obstruction.

PMID- 30185521
TI  - Prostate cancer screening with prostate-specific antigen (PSA) test: a systematic
      review and meta-analysis.
AB  - OBJECTIVE: To investigate the efficacy and safety of prostate-specific antigen
      (PSA) testing to screen for prostate cancer. DESIGN: Systematic review and meta
      analysis. DATA SOURCES: Electronic search of Cochrane Central Register of
      Controlled Trials, Web of Science, Embase, Scopus, OpenGrey, LILACS, and Medline,
      and search of scientific meeting abstracts and trial registers to April 2018.
      ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials
      comparing PSA screening with usual care in men without a diagnosis of prostate
      cancer. DATA EXTRACTION: At least two reviewers screened studies, extracted data,
      and assessed the quality of eligible studies. A parallel guideline committee (BMJ
      Rapid Recommendation) provided input on the design and interpretation of the
      systematic review, including selection of outcomes important to patients. We used
      a random effects model to obtain pooled incidence rate ratios (IRR) and, when
      feasible, conducted subgroup analyses (defined a priori) based on age, frequency
      of screening, family history, ethnicity, and socioeconomic level, as well as a
      sensitivity analysis based on the risk of bias. The quality of the evidence was
      assessed with the GRADE approach. RESULTS: Five randomised controlled trials,
      enrolling 721 718 men, were included. Studies varied with respect to screening
      frequency and intervals, PSA thresholds for biopsy, and risk of bias. When
      considering the whole body of evidence, screening probably has no effect on all
      cause mortality (IRR 0.99, 95% CI 0.98 to 1.01; moderate certainty) and may have
      no effect on prostate-specific mortality (IRR 0.96, 0.85 to 1.08; low certainty).
      Sensitivity analysis of studies at lower risk of bias (n=1) also demonstrates
      that screening seems to have no effect on all-cause mortality (IRR 1.0, 0.98 to
      1.02; moderate certainty) but may have a small effect on prostate-specific
      mortality (IRR 0.79, 0.69 to 0.91; moderate certainty). This corresponds to one
      less death from prostate cancer per 1000 men screened over 10 years. Direct
      comparative data on biopsy and treatment related complications from the included
      trials were limited. Using modelling, we estimated that for every 1000 men
      screened, approximately 1, 3, and 25 more men would be hospitalised for sepsis,
      require pads for urinary incontinence, and report erectile dysfunction,
      respectively. CONCLUSIONS: At best, screening for prostate cancer leads to a
      small reduction in disease-specific mortality over 10 years but has does not
      affect overall mortality. Clinicians and patients considering PSA based screening
      need to weigh these benefits against the potential short and long term harms of
      screening, including complications from biopsies and subsequent treatment, as
      well as the risk of overdiagnosis and overtreatment. SYSTEMATIC REVIEW
      REGISTRATION: PROSPERO registration number CRD42016042347.

PMID- 30185522
TI  - A quarter of people are not being active enough to stay healthy.

PMID- 30185523
TI  - C-type lectin-like receptor 2 (CLEC-2)-dependent dendritic cell migration is
      controlled by tetraspanin CD37.
AB  - Cell migration is central to evoking a potent immune response. Dendritic cell
      (DC) migration to lymph nodes is dependent on the interaction of C-type lectin
      like receptor 2 (CLEC-2; encoded by the gene Clec1b), expressed by DCs, with
      podoplanin, expressed by lymph node stromal cells, although the underlying
      molecular mechanisms remain elusive. Here, we show that CLEC-2-dependent DC
      migration is controlled by tetraspanin CD37, a membrane-organizing protein. We
      identified a specific interaction between CLEC-2 and CD37, and myeloid cells
      lacking CD37 (Cd37 -/-) expressed reduced surface CLEC-2. CLEC-2-expressing Cd37 
      /- DCs showed impaired adhesion, migration velocity and displacement on lymph
      node stromal cells. Moreover, Cd37 -/- DCs failed to form actin protrusions in a
      3D collagen matrix upon podoplanin-induced CLEC-2 stimulation, phenocopying CLEC
      2-deficient DCs. Microcontact printing experiments revealed that CD37 is required
      for CLEC-2 recruitment in the membrane to its ligand podoplanin. Finally, Cd37 -/
      DCs failed to inhibit actomyosin contractility in lymph node stromal cells, thus
      phenocopying CLEC-2-deficient DCs. This study demonstrates that tetraspanin CD37
      controls CLEC-2 membrane organization and provides new molecular insights into
      the mechanisms underlying CLEC-2-dependent DC migration.This article has an
      associated First Person interview with the first author of the paper.

PMID- 30185524
TI  - Microtubule dynamics regulation reconstituted in budding yeast lysates.
AB  - Microtubules (MTs) are important for cellular structure, transport of cargoes and
      segregation of chromosomes and organelles during mitosis. The stochastic growth
      and shrinkage of MTs, known as dynamic instability, is necessary for these
      functions. Previous studies to determine how individual MT-associated proteins
      (MAPs) affect MT dynamics have been performed either through in vivo studies,
      which provide limited opportunity for observation of individual MTs or
      manipulation of conditions, or in vitro studies, which focus either on purified
      proteins, and therefore lack cellular complexity, or on cell extracts made from
      genetically intractable organisms. In order to investigate the ensemble
      activities of all MAPs on MT dynamics using lysates made from a genetically
      tractable organism, we developed a cell-free assay for budding yeast lysates
      using total internal reflection fluorescence (TIRF) microscopy. Lysates were
      prepared from yeast strains expressing GFP-tubulin. MT polymerization from pre
      assembled MT seeds adhered to a coverslip was observed in real time. Through use
      of cell division cycle (cdc) and MT depolymerase mutants, we found that MT
      polymerization and dynamic instability are dependent on the cell cycle state and
      the activities of specific MAPs.

PMID- 30185527
TI  - Twitter helped me decide that I'm not for resuscitation.

PMID- 30185525
TI  - Chronic starvation induces noncanonical pro-death stress granules.
AB  - Stress granules (SGs) assemble under stress-induced conditions that inhibit
      protein synthesis, including phosphorylation of eIF2alpha, inhibition of the RNA
      helicase eIF4a proteins or inactivation of mTORC1. Classically defined SGs are
      composed of translation initiation factors, 40S ribosomes, RNA-binding proteins
      and poly(A)+ mRNAs. As such, they represent an important compartment for storage
      of mRNAs and regulation of their translation. Emerging work on SGs indicates that
      these structures might promote cellular survival in diverse disease states. Yet,
      much work on SG formation and function employs acute stress conditions, which
      might not accurately reflect the chronic stresses that manifest in human disease.
      Here, we used prolonged nutrient starvation to model and investigate SG formation
      and function during chronic stress in a human cell line and mouse embryonic
      fibroblasts. Surprisingly, we found that SGs that form under chronic nutrient
      starvation lack 40S ribosomes, do not actively exchange their constituent
      components with cytoplasmic pools and promote cell death. We named these SGs
      starvation-induced SGs (stSGs). Our results on stSGs imply that SG assembly and
      function in the context of prolonged nutrient starvation stress differ
      significantly from what has been described for acute stress conditions.

PMID- 30185528
TI  - Removing financial incentives for GPs led to decline in performance, finds study.

PMID- 30185529
TI  - What should doctors say to men asking for a PSA test?

PMID- 30185526
TI  - RSPH6A is required for sperm flagellum formation and male fertility in mice.
AB  - The flagellum is an evolutionarily conserved appendage used for sensing and
      locomotion. Its backbone is the axoneme and a component of the axoneme is the
      radial spoke (RS), a protein complex implicated in flagellar motility regulation.
      Numerous diseases occur if the axoneme is improperly formed, such as primary
      ciliary dyskinesia (PCD) and infertility. Radial spoke head 6 homolog A (RSPH6A)
      is an ortholog of Chlamydomonas RSP6 in the RS head and is evolutionarily
      conserved. While some RS head proteins have been linked to PCD, little is known
      about RSPH6A. Here, we show that mouse RSPH6A is testis-enriched and localized in
      the flagellum. Rsph6a knockout (KO) male mice are infertile as a result of their
      short immotile spermatozoa. Observation of the KO testis indicates that the
      axoneme can elongate but is disrupted before accessory structures are formed.
      Manchette removal is also impaired in the KO testis. Further, RSPH9, another
      radial spoke protein, disappeared in the Rsph6a KO flagella. These data indicate
      that RSPH6A is essential for sperm flagellar assembly and male fertility in
      mice.This article has an associated First Person interview with the first author
      of the paper.

PMID- 30185530
TI  - Cytotoxic effects of heated tobacco products (HTP) on human bronchial epithelial
      cells.
AB  - BACKGROUND: Heated tobacco product(s) (HTP), also called heat-not-burn products,
      are a re-emerging class of tobacco products that purport to reduce health risk
      compared with smoking combustible tobacco products. This study examined the
      potential toxic effects of inhaling emissions from an HTP in comparison with
      electronic and combustible tobacco cigarettes. METHODS: Inhalation toxicity of
      HTP (IQOS; tobacco flavour), e-cigarette (MarkTen; tobacco flavour) and tobacco
      cigarette (Marlboro Red) was examined in vitro using an air-liquid interface with
      human bronchial epithelial cells (H292). Cells were exposed directly to 55 puffs
      from the e-cigarette, 12 puffs from the HTP and 8 puffs from the tobacco
      cigarette to equilibrate nicotine delivery to the cells across products.
      Cytotoxicity was measured using neutral red uptake and trypan blue assays.
      Cytotoxic effects of each tested product (HTP, e-cigarette and tobacco cigarette)
      were compared with an air control. Release of inflammatory markers (cytokines)
      was measured using ELISA. RESULTS: The HTP showed higher cytotoxicity compared
      with the air controls using the neutral red assay. The HTP also showed higher
      cytotoxicity than the e-cigarette, but lower cytotoxicity than the combustible
      cigarettes using the same assay. A significant increase in cytokines levels,
      compared with air controls, was observed postexposure to tobacco smoke but not to
      emissions from HTP or e-cigarette aerosol. DISCUSSION: Using limited cytotoxic
      measures, the HTP showed reduced cytotoxicity relative to a combustible cigarette
      but higher toxicity than an e-cigarette. More comprehensive testing is needed to
      determine long-term effects of inhaling emissions from HTP.

PMID- 30185532
TI  - Upward intergenerational transmission of health inequality.

PMID- 30185531
TI  - Youth access to JUUL online: eBay sales of JUUL prior to and following FDA
      action.
AB  - BACKGROUND: The novel e-cigarette product JUUL has experienced rapid market
      growth. The online auction site eBay has been mentioned as a source of JUUL
      access for youth, and the US Food and Drug Administration (FDA) notified eBay to
      remove JUUL listings in April 2018. We sought to characterise the sale of JUUL
      products on eBay prior to the FDA's request, document the impact of this request
      and explore ways in which eBay vendors bypassed this effort. METHODS: eBay was
      searched for JUUL-branded products sold by US vendors in March 2018, yielding a
      sample of 197 listings for devices and/or pods. Each listing was coded for
      product, listing and youth access content. Following FDA action, each listing was
      revisited to determine its status, and each vendor's page was searched for JUUL
      and other vaping content. Data were analysed using descriptive statistics.
      RESULTS: Of 197 eBay listings, 189 were for JUUL kits and 13 were for pods.
      Prices were on average higher than those on the official JUUL store, and language
      about age restrictions was rare. Following FDA contact, most listings were no
      longer active. However, 3.4% of these vendors still sold JUUL devices or pods and
      15.5% were selling other vaporisers or nicotine products. CONCLUSIONS: Online
      platforms may lack the will or expertise to effectively monitor content for
      tobacco products, while vendors quickly adapt to minor changes with simple
      strategies such as spelling variations. Accurate identification of online e
      cigarette vendors is essential to the enforcement of policy and may benefit from
      cross-sector partnerships.

PMID- 30185533
TI  - Spillover effects of children's political status on elderly parents' health in
      China.
AB  - BACKGROUND: Due to the sustained increases in life expectancy over the past half
      century, the elderly today will receive supports from their children for a longer
      period than ever before. Therefore, understanding the spillover effects of
      children's socioeconomic status on parents' health becomes increasingly important
      for both scholars and policy makers. METHODS: The Ordinary Least Squares
      regression is applied to the China Health and Retirement Longitudinal Study 2011,
      a national representative dataset including approximately 10 000 households and
      17 600 middle-aged and elderly respondents. The Sobel test is used to examine the
      mediation role of social integration. RESULTS: The elderly who have a cadre child
      reported better health (coefficient=0.1347; 95% CI 0.067 to 0.202), had fewer
      activities of daily living (ADLs) limitations (coefficient=-0.1289; 95% CI -0.216
      to -0.042) and were more socially integrated (coefficient=0.2321; 95% CI 0.103 to
      0.361). Such effects are mainly driven by the parents of higher-ranking cadres.
      For the parents of higher ranking cadres, the Sobel test suggests that 12.6% of
      the total effects on self-reported health and 21.9% of the total effects on ADL
      limitations are mediated by the increase in parents' social integration.
      CONCLUSION: The findings suggest positive spillover effects of children's
      political status on parents' health. The benefits of having a cadre child are at
      least equivalent to the rural-urban gap in health and even stronger for the
      parents of higher ranking cadres. One potential explanation for such spillover
      effects is that a child's political status can improve parents' community
      involvement and social interactions.

PMID- 30185534
TI  - Reduced expression of SIRT1 and SOD-1 and the correlation between these levels in
      various regions of the brains of patients with Alzheimer's disease.
AB  - AIMS: This study was designed to explore the expression and distribution of
      silent information regulator 1 (SIRT1) and superoxide dismutase 1 (SOD-1) in
      various regions of the brains of patients with Alzheimer's disease (AD), as well
      as to assess potential correlations between the levels of these proteins and also
      between these proteins and the Braak stage of AD. METHODS: In the temporal and
      frontal cortices, hippocampus and cerebellum of 10 patients with AD and 10 age
      matched control subjects, expression of SIRT1 and SOD-1, together with
      histopathology, were assessed by immunohistochemical and immunofluorescent
      stainings. Relationships between variables were examined with the Pearson
      correlation test. RESULTS: The numbers of both SIRT1-positive and SOD-1-positive
      neurons and integrated optical density of immunohistochemical staining for these
      proteins in the temporal and frontal cortices, and hippocampus of patients with
      AD were significantly decreased than those in corresponding controls. In the case
      of the cerebellum, very weak expression of SIRT1 and obvious expression of SOD-1
      were observed in granule cells, with no significant difference between AD and the
      control group. Interestingly, the protein levels between SIRT1 and SOD-1, as well
      as the level of SIRT1 or SOD-1 and Braak stage, were significantly correlated in
      neurons in all regions of the AD brains investigated except for the cerebellum.
      CONCLUSIONS: These findings indicate that the reduced level of SIRT1 in the
      brains of patients with AD may be related to the decline in SOD-1 and
      neuropathological changes of this disorder.

PMID- 30185535
TI  - Cervical Cancer Burden and Opportunities for Prevention in a Safety-Net
      Healthcare System.
AB  - BACKGROUND: The high prevalence of cervical cancer at safety-net health systems
      requires careful analysis to best inform prevention and quality improvement
      efforts. We characterized cervical cancer burden and identified opportunities for
      prevention in a U.S. safety-net system. METHODS: We reviewed tumor registry and
      electronic health record (EHR) data of women with invasive cervical cancer with
      ages 18+, diagnosed between 2010 and 2015, in a large, integrated urban safety
      net. We developed an algorithm to: (i) classify whether women had been engaged in
      care (>=1 clinical encounter between 6 months and 5 years before cancer
      diagnosis); and (ii) identify missed opportunities (no screening, no follow-up,
      failure of a test to detect cancer, and treatment failure) and associated factors
      among engaged patients. RESULTS: Of 419 women with cervical cancer, more than
      half (58%) were stage 2B or higher at diagnosis and 40% were uninsured. Most
      (69%) had no prior healthcare system contact; 47% were diagnosed elsewhere. Among
      122 engaged in care prior to diagnosis, failure to screen was most common (63%),
      followed by lack of follow-up (21%), and failure of test to detect cancer (16%).
      Tumor stage, patient characteristics, and healthcare utilization differed across
      groups. CONCLUSIONS: Safety-net healthcare systems face a high cervical cancer
      burden, mainly from women with no prior contact with the system. To prevent or
      detect cancer early, community-based efforts should encourage uninsured women to
      use safety-nets for primary care and preventive services. IMPACT: Among engaged
      patients, strategies to increase screening and follow-up of abnormal screening
      tests could prevent over 80% of cervical cancer cases.

PMID- 30185537
TI  - SIRT1: A Novel Way to Target Tau?

PMID- 30185538
TI  - The Impact of Non-Neurotropic Influenza Strains on the Brain: A Role for
      Microglial Priming?

PMID- 30185536
TI  - DNA Methylation of LRRC3B: A Biomarker for Survival of Early-Stage Non-Small Cell
      Lung Cancer Patients.
AB  - BACKGROUND: Previous studies support a tumor-suppressor role for LRRC3B across
      various types of cancers. We aimed to investigate the association between DNA
      methylation of LRRC3B and overall survival (OS) for patients with early-stage non
      small cell lung cancer (NSCLC). METHODS: This study included 1,230 patients with
      early-stage NSCLC. DNA was extracted from lung tumor tissues and DNA methylation
      was measured using Illumina Infinium HumanMethylation450 BeadChips. The
      association between DNA methylation and OS was first tested using Cox regression
      on a discovery cohort and then validated in an independent cohort. Next, the
      association between DNA methylation and gene expression was investigated in two
      independent cohorts. Finally, the association between gene expression and OS was
      investigated in three independent groups of patients. RESULTS: Three novel DNA
      methylation sites in LRRC3B were significantly associated with OS in two groups
      of patients. Patients with hypermethylation in the DNA methylation sites had
      significantly longer survival than the others in both the discovery cohort (HR,
      0.62; P = 2.02 * 10-05) and validation cohort (HR, 0.55; P = 4.44 * 10-04). The
      three DNA methylation sites were significantly associated with LRRC3B expression,
      which was also associated with OS. CONCLUSIONS: Using clinical data from a large
      population, we illustrated the association between DNA methylation of LRRC3B and
      OS of early-stage NSCLC. IMPACT: We provide evidence of plausibility for building
      biomarkers on DNA methylation of LRRC3B for OS of early-stage NSCLC, thus filling
      a gap between previous in vitro studies and clinical applications.

PMID- 30185540
TI  - Economic evaluations of strategies to prevent sports and recreational injury
      among children and adolescents: a systematic review.
AB  - OBJECTIVE: To identify, summarise and critically assess studies reporting costs
      and consequences of sport and recreation injury prevention strategies among
      children and adolescents. DESIGN: Systematic review. METHODS AND DATA SOURCES: We
      searched MEDLINE (Ovid), EMBASE, CINAHL, Pubmed, Econlit and SPORTDiscus and
      PEDE. Included studies were peer reviewed full economic evaluations or cost
      analyses of sport/recreation injury prevention among children and adolescents<=18
      years of age. The Pediatric Quality Appraisal Questionnaire was used for quality
      assessment. RESULTS: The initial search yielded 1896 unique records; eight
      studies met inclusion criteria. Six studies were related to injury prevention in
      the context of recreation, two were related to sports. For recreation studies in
      cycling and swimming: costs per head injury averted was US$3109 to $228 197;
      costs per hospitalisation avoided was US$3526 to 872 794; cost per life
      saved/death avoided was US$3531 to $103 518 154. Sport interventions in hockey
      and soccer were cost saving (fewer injuries and lower costs). Global quality
      assessments ranged from poor to good. Important limitations included short time
      horizons and intermediate outcome measures. CONCLUSIONS: Few rigorous economic
      evaluations related to sport and recreation injury prevention have been
      conducted. The range of estimates and variation in outcomes used preclude
      specific conclusions; however, where strategies both improve health and are cost
      saving, implementation should be prioritised. Future economic evaluations should
      incorporate time horizons sufficient to capture changes in long-term health and
      use utility-based outcome measures in order to capture individual preferences for
      changes in health states and facilitate comparison across intervention types.

PMID- 30185539
TI  - Evaluating the Columnar Stability of Acoustic Processing in the Human Auditory
      Cortex.
AB  - Using ultra-high field fMRI, we explored the cortical depth-dependent stability
      of acoustic feature preference in human auditory cortex. We collected responses
      from human auditory cortex (subjects from either sex) to a large number of
      natural sounds at submillimeter spatial resolution, and observed that these
      responses were well explained by a model that assumes neuronal population tuning
      to frequency-specific spectrotemporal modulations. We observed a relatively
      stable (columnar) tuning to frequency and temporal modulations. However, spectral
      modulation tuning was variable throughout the cortical depth. This difference in
      columnar stability between feature maps could not be explained by a difference in
      map smoothness, as the preference along the cortical sheet varied in a similar
      manner for the different feature maps. Furthermore, tuning to all three features
      was more columnar in primary than nonprimary auditory cortex. The observed
      overall lack of overlapping columnar regions across acoustic feature maps
      suggests, especially for primary auditory cortex, a coding strategy in which
      across cortical depths tuning to some features is kept stable, whereas tuning to
      other features systematically varies.SIGNIFICANCE STATEMENT In the human auditory
      cortex, sound aspects are processed in large-scale maps. Invasive animal studies
      show that an additional processing organization may be implemented orthogonal to
      the cortical sheet (i.e., in the columnar direction), but it is unknown whether
      observed organizational principles apply to the human auditory cortex. Combining
      ultra-high field fMRI with natural sounds, we explore the columnar organization
      of various sound aspects. Our results suggest that the human auditory cortex
      contains a modular coding strategy, where, for each module, several sound aspects
      act as an anchor along which computations are performed while the processing of
      another sound aspect undergoes a transformation. This strategy may serve to
      optimally represent the content of our complex acoustic natural environment.

PMID- 30185541
TI  - Rejuvenating functional responses with renewal theory.
AB  - Functional responses are widely used to describe interactions and resource
      exchange between individuals in ecology. The form given to functional responses
      dramatically affects the dynamics and stability of populations and communities.
      Despite their importance, functional responses are generally considered with a
      phenomenological approach, without clear mechanistic justifications from
      individual traits and behaviours. Here, we develop a bottom-up stochastic
      framework grounded in renewal theory that shows how functional responses emerge
      from the level of the individuals through the decomposition of interactions into
      different activities. Our framework has many applications for conceptual,
      theoretical and empirical purposes. First, we show how the mean and variance of
      classical functional responses are obtained with explicit ecological assumptions,
      for instance regarding foraging behaviours. Second, we give examples in specific
      ecological contexts, such as in nuptial-feeding species or size-dependent
      handling times. Finally, we demonstrate how to analyse data with our framework,
      especially highlighting that observed variability in the number of interactions
      can be used to infer parameters and compare functional response models.

PMID- 30185542
TI  - Computational modelling suggests complex interactions between interstitial flow
      and tumour angiogenesis.
AB  - Angiogenesis, the growth of capillaries from pre-existing ones, plays a key role
      in cancer progression. Tumours release tumour angiogenic factors (TAFs) into the
      extracellular matrix (ECM) that trigger angiogenesis once they reach the
      vasculature. The neovasculature provides nutrients and oxygen to the tumour. In
      the ECM, the interstitial fluid moves driven by pressure differences and may
      affect the distribution of tumour TAFs, and, in turn, tumour vascularization. In
      this work, we propose a hybrid mathematical model to investigate the influence of
      fluid flow in tumour angiogenesis. Our model shows the impact of interstitial
      flow in a time-evolving capillary network using a continuous approach. The flow
      model is coupled to a model of angiogenesis that includes tip endothelial cells,
      filopodia, capillaries and TAFs. The TAF transport equation considers not only
      diffusive mechanisms but also the convective transport produced by interstitial
      flow. Our simulations predict a significant alteration of the new vascular
      networks, which tend to grow more prominently against the flow. The model
      suggests that interstitial flow may produce increased tumour malignancies and
      hindered treatments.

PMID- 30185544
TI  - Detection of HIV transmission clusters from phylogenetic trees using a multi
      state birth-death model.
AB  - HIV patients form clusters in HIV transmission networks. Accurate identification
      of these transmission clusters is essential to effectively target public health
      interventions. One reason for clustering is that the underlying contact network
      contains many local communities. We present a new maximum-likelihood method for
      identifying transmission clusters caused by community structure, based on
      phylogenetic trees. The method employs a multi-state birth-death (MSBD) model
      which detects changes in transmission rate, which are interpreted as the
      introduction of the epidemic into a new susceptible community, i.e. the formation
      of a new cluster. We show that the MSBD method is able to reliably infer the
      clusters and the transmission parameters from a pathogen phylogeny based on our
      simulations. In contrast to existing cutpoint-based methods for cluster
      identification, our method does not require that clusters be monophyletic nor is
      it dependent on the selection of a difficult-to-interpret cutpoint parameter. We
      present an application of our method to data from the Swiss HIV Cohort Study. The
      method is available as an easy-to-use R package.

PMID- 30185543
TI  - Origin of biomolecular games: deception and molecular evolution.
AB  - Biological macromolecules encode information: some of it to endow the molecule
      with structural flexibility, some of it to enable molecular actions as a catalyst
      or a substrate, but a residual part can be used to communicate with other
      macromolecules. Thus, macromolecules do not need to possess information only to
      survive in an environment, but also to strategically interact with others by
      sending signals to a receiving macromolecule that can properly interpret the
      signal and act suitably. These sender-receiver signalling games are sustained by
      the information asymmetry that exists among the macromolecules. In both
      biochemistry and molecular evolution, the important role of information asymmetry
      remains largely unaddressed. Here, we provide a new unifying perspective on the
      impact of information symmetry between macromolecules on molecular evolutionary
      processes, while focusing on molecular deception. Biomolecular games arise from
      the ability of biological macromolecules to exert precise recognition, and their
      role as units of selection, meaning that they are subject to competition and
      cooperation with other macromolecules. Thus, signalling game theory can be used
      to better understand fundamental features of living systems such as molecular
      recognition, molecular mimicry, selfish elements and 'junk' DNA. We show how
      deceptive behaviour at the molecular level indicates a conflict of interest, and
      so provides evidence of genetic conflict. This model proposes that molecular
      deception is diagnostic of selfish behaviour, helping to explain the evasive
      behaviour of transposable elements in 'junk' DNA, for example. Additionally, in
      this broad review, a range of major evolutionary transitions are shown to be
      associated with the establishment of signalling conventions, many of which are
      susceptible to molecular deception. These perspectives allow us to assign
      rudimentary behaviour to macromolecules, and show how participation in signalling
      games differentiates biochemistry from abiotic chemistry.

PMID- 30185545
TI  - Prostate cancer screening with prostate-specific antigen (PSA) test: a clinical
      practice guideline.

PMID- 30185546
TI  - HORMAD1 Is a Negative Prognostic Indicator in Lung Adenocarcinoma and Specifies
      Resistance to Oxidative and Genotoxic Stress.
AB  - Cancer testis antigens (CTA) are expressed in testis and placenta and anomalously
      activated in a variety of tumors. The mechanistic contribution of CTAs to
      neoplastic phenotypes remains largely unknown. Using a chemigenomics approach, we
      find that the CTA HORMAD1 correlates with resistance to the mitochondrial complex
      I inhibitor piericidin A in non-small cell lung cancer (NSCLC). Resistance was
      due to a reductive intracellular environment that attenuated the accumulation of
      free radicals. In human lung adenocarcinoma (LUAD) tumors, patients expressing
      high HORMAD1 exhibited elevated mutational burden and reduced survival. HORMAD1
      tumors were enriched for genes essential for homologous recombination (HR), and
      HORMAD1 promoted RAD51-filament formation, but not DNA resection, during HR.
      Accordingly, HORMAD1 loss enhanced sensitivity to gamma-irradiation and PARP
      inhibition, and HORMAD1 depletion significantly reduced tumor growth in vivo
      These results suggest that HORMAD1 expression specifies a novel subtype of LUAD,
      which has adapted to mitigate DNA damage. In this setting, HORMAD1 could
      represent a direct target for intervention to enhance sensitivity to DNA-damaging
      agents or as an immunotherapeutic target in patients.Significance: This study
      uses a chemigenomics approach to demonstrate that anomalous expression of the CTA
      HORMAD1 specifies resistance to oxidative stress and promotes HR to support tumor
      cell survival in NSCLC. Cancer Res; 78(21); 6196-208. (c)2018 AACR.

PMID- 30185548
TI  - Dual Inhibition of DNA and Histone Methyltransferases Increases Viral Mimicry in
      Ovarian Cancer Cells.
AB  - Ovarian cancer ranks as the most deadly gynecologic cancer, and there is an
      urgent need to develop more effective therapies. Previous studies have shown that
      G9A, a histone methyltransferase that catalyzes mono- and dimethylation of
      histone H3 lysine9, is highly expressed in ovarian cancer tumors, and its
      overexpression is associated with poor prognosis. Here we report that
      pharmacologic inhibition of G9A in ovarian cancer cell lines with high levels of
      G9A expression induces synergistic antitumor effects when combined with the DNA
      methylation inhibitor (DNMTi) 5-aza-2'-deoxycytidine (5-aza-CdR). These antitumor
      effects included upregulation of endogenous retroviruses (ERV), activation of the
      viral defense response, and induction of cell death, which have been termed
      "viral mimicry" effects induced by DNMTi. G9Ai treatment further reduced H3K9me2
      levels within the long terminal repeat regions of ERV, resulting in further
      increases of ERV expression and enhancing "viral mimicry" effects. In contrast,
      G9Ai and 5-aza-CdR were not synergistic in cell lines with low basal G9A levels.
      Taken together, our results suggest that the synergistic effects of combination
      treatment with DNMTi and G9Ai may serve as a novel therapeutic strategy for
      patients with ovarian cancer with high levels of G9A expression.Significance:
      Dual inhibition of DNA methylation and histone H3 lysine 9 dimethylation by 5-aza
      CdR and G9Ai results in synergistic upregulation of ERV and induces an antiviral
      response, serving as a basis for exploring this novel combination treatment in
      patients with ovarian cancer. Cancer Res; 78(20); 5754-66. (c)2018 AACR.

PMID- 30185549
TI  - CDK8 Selectively Promotes the Growth of Colon Cancer Metastases in the Liver by
      Regulating Gene Expression of TIMP3 and Matrix Metalloproteinases.
AB  - : Unresectable hepatic metastases of colon cancer respond poorly to existing
      therapies and are a major cause of colon cancer lethality. In this study, we
      evaluated the therapeutic viability of targeting the mediator kinase CDK8, an
      early clinical stage drug target, as a means to suppress metastasis of colon
      cancer. CDK8 was amplified or overexpressed in many colon cancers and CDK8
      expression correlated with shorter patient survival. Knockdown or inhibition of
      CDK8 had little effect on colon cancer cell growth but suppressed metastatic
      growth of mouse and human colon cancer cells in the liver. This effect was due in
      part to inhibition of already established hepatic metastases, indicating
      therapeutic potential of CDK8 inhibitors in the metastatic setting. In contrast,
      knockdown or inhibition of CDK8 had no significant effect on the growth of tumors
      implanted subcutaneously, intrasplenically, or orthotopically in the cecum. CDK8
      mediated colon cancer growth in the liver through downregulation of matrix
      metalloproteinase (MMP) inhibitor TIMP3 via TGFbeta/SMAD-driven expression of a
      TIMP3-targeting microRNA, miR-181b, along with induction of Mmp3 in murine or
      MMP9 in human colon cancer cells via Wnt/beta-catenin-driven transcription. These
      findings reveal a new mechanism for negative regulation of gene expression by
      CDK8 and a site-specific role for CDK8 in colon cancer hepatic metastasis. Our
      results indicate the utility of CDK8 inhibitors for the treatment of colon cancer
      metastases in the liver and suggest that CDK8 inhibitors may be considered in
      other therapeutic settings involving TGFbeta/SMAD or Wnt/beta-catenin pathway
      activation. SIGNIFICANCE: These findings demonstrate that inhibition of the
      transcription-regulating kinase CDK8 exerts a site-specific tumor-suppressive
      effect on colon cancer growth in the liver, representing a unique therapeutic
      opportunity for the treatment of advanced colon cancer.Graphical Abstract:
      http://cancerres.aacrjournals.org/content/canres/78/23/6594/F1.large.jpg.

PMID- 30185550
TI  - VEGFC Antibody Therapy Drives Differentiation of AML.
AB  - High expression of VEGFC predicts adverse prognosis in acute myeloid leukemia
      (AML). We therefore explored VEGFC-targeting efficacy as an AML therapy using a
      VEGFC mAb. VEGFC antibody therapy enforced myelocytic differentiation of clonal
      CD34+ AML blasts. Treatment of CD34+ AML blasts with the antibody reduced
      expansion potential by 30% to 50% and enhanced differentiation via FOXO3A
      suppression and inhibition of MAPK/ERK proliferative signals. VEGFC antibody
      therapy also accelerated leukemia cell differentiation in a systemic humanized
      AML mouse model. Collectively, these results define a regulatory function of
      VEGFC in CD34+ AML cell fate decisions via FOXO3A and serve as a new potential
      differentiation therapy for patients with AML.Significance: These findings reveal
      VEGFC targeting as a promising new differentiation therapy in AML. Cancer Res;
      78(20); 5940-8. (c)2018 AACR.

PMID- 30185547
TI  - Pooled Analysis of Nine Cohorts Reveals Breast Cancer Risk Factors by Tumor
      Molecular Subtype.
AB  - Various subtypes of breast cancer defined by estrogen receptor (ER), progesterone
      receptor (PR), and HER2 exhibit etiologic differences in reproductive factors,
      but associations with other risk factors are inconsistent. To clarify etiologic
      heterogeneity, we pooled data from nine cohort studies. Multivariable, joint Cox
      proportional hazards regression models were used to estimate HRs and 95%
      confidence intervals (CI) for molecular subtypes. Of 606,025 women, 11,741
      invasive breast cancers with complete tissue markers developed during follow-up:
      8,700 luminal A-like (ER+ or PR+/HER2-), 1,368 luminal B-like (ER+ or PR+/HER2+),
      521 HER2-enriched (ER-/PR-/HER2+), and 1,152 triple-negative (ER-/PR-/HER2-)
      disease. Ever parous compared with never was associated with lower risk of
      luminal A-like (HR, 0.78; 95% CI, 0.73-0.83) and luminal B-like (HR, 0.74; 95%
      CI, 0.64-0.87) as well as a higher risk of triple-negative disease (HR, 1.23; 95%
      CI, 1.02-1.50; P value for overall tumor heterogeneity < 0.001). Direct
      associations with luminal-like, but not HER2-enriched or triple-negative, tumors
      were found for age at first birth, years between menarche and first birth, and
      age at menopause (P value for overall tumor heterogeneity < 0.001). Age-specific
      associations with baseline body mass index differed for risk of luminal A-like
      and triple-negative breast cancer (P value for tumor heterogeneity = 0.02). These
      results provide the strongest evidence for etiologic heterogeneity of breast
      cancer to date from prospective studies.Significance: These findings comprise the
      largest study of prospective data to date and contribute to the accumulating
      evidence that etiological heterogeneity exists in breast carcinogenesis. Cancer
      Res; 78(20); 6011-21. (c)2018 AACR.

PMID- 30185551
TI  - Induction of Paracrine Signaling in Metastatic Melanoma Cells by PPARgamma
      Agonist Rosiglitazone Activates Stromal Cells and Enhances Tumor Growth.
AB  - In addition to improving insulin sensitivity in type 2 diabetes, the
      thiazolidinedione family of compounds and the pharmacologic activation of their
      best-characterized target PPARgamma have been proposed as a therapeutic option
      for cancer treatment. In this study, we reveal a new mode of action for the
      thiazolidinedione rosiglitazone that can contribute to tumorigenesis.
      Rosiglitazone activated a tumorigenic paracrine communication program in a subset
      of human melanoma cells that involves the secretion of cytokines, chemokines, and
      angiogenic factors. This complex blend of paracrine signals activated
      nonmalignant fibroblasts, endothelial cells, and macrophages in a tumor-friendly
      way. In agreement with these data, rosiglitazone promoted human melanoma
      development in xenografts, and tumors exposed to rosiglitazone exhibited enhanced
      angiogenesis and inflammation. Together, these findings establish an important
      tumorigenic action of rosiglitazone in a subset of melanoma cells. Although
      studies conducted on cohorts of diabetic patients report overall benefits of
      thiazolidinediones in cancer prevention, our data suggest that exposure of
      established tumors to rosiglitazone may be deleterious.Significance: These
      findings uncover a novel mechanism by which the thiazolidinedione compound
      rosiglitazone contributes to tumorigenesis, thus highlighting a potential risk
      associated with its use in patients with established tumors. Cancer Res; 78(22);
      6447-61. (c)2018 AACR.

PMID- 30185552
TI  - EGR1-Mediated Transcription of lncRNA-HNF1A-AS1 Promotes Cell-Cycle Progression
      in Gastric Cancer.
AB  - Long noncoding RNAs (lncRNA) are dysregulated in various human cancers and
      control tumor development and progression. However, the upstream mechanisms
      underlying their dysregulation remain unclear. Here, we demonstrate that the
      expression of hepatocyte nuclear factor 1 homeobox A antisense RNA 1 (HNF1A-AS1)
      is significantly upregulated in gastric cancer tissues. Overexpression of HNF1A
      AS1 enhanced cell proliferation and promoted cell-cycle progression, whereas
      knockdown of HNF1A-AS1 elicited the opposite effects. Early growth response
      protein 1 (EGR1) directly bound the HNF1A-AS1 promoter region and activated its
      transcription. Overexpression of EGR1 enhanced cell proliferation and promoted
      cell-cycle promotion, similar to the function of HNF1A-AS1. HNF1A-AS1 functioned
      as competing endogenous RNA (ceRNA) by binding to miR-661, upregulating the
      expression of cell division cycle 34 (CDC34), which is a direct target of miR
      661. EGR1 and HNF1A-AS1 enhanced the expression of cyclin-dependent kinase 2
      (CDK2), CDK4, and cyclin E1 but inhibited the expression of p21 by promoting
      CDC34-mediated ubiquitination and degradation of p21. Taken together, these
      findings suggest that EGR1-activated HNF1A-AS1 regulates various pro- and
      antigrowth factors to promote the development of gastric cancer, implicating it
      as a possible target for therapeutic intervention in this disease.Significance:
      This study provides novel insights into mechanisms by which the noncoding RNA
      HNF1A-AS1 contributes to gastric cancer progression through modulation of the
      cell cycle. Cancer Res; 78(20); 5877-90. (c)2018 AACR.

PMID- 30185553
TI  - Altered ER-mitochondria contact impacts mitochondria calcium homeostasis and
      contributes to neurodegeneration in vivo in disease models.
AB  - Calcium (Ca2+) homeostasis is essential for neuronal function and survival.
      Altered Ca2+ homeostasis has been consistently observed in neurological diseases.
      How Ca2+ homeostasis is achieved in various cellular compartments of disease
      relevant cell types is not well understood. Here we show in Drosophila
      Parkinson's disease (PD) models that Ca2+ transport from the endoplasmic
      reticulum (ER) to mitochondria through the ER-mitochondria contact site (ERMCS)
      critically regulates mitochondrial Ca2+ (mito-Ca2+) homeostasis in dopaminergic
      (DA) neurons, and that the PD-associated PINK1 protein modulates this process. In
      PINK1 mutant DA neurons, the ERMCS is strengthened and mito-Ca2+ level is
      elevated, resulting in mitochondrial enlargement and neuronal death. Miro, a well
      characterized component of the mitochondrial trafficking machinery, mediates the
      effects of PINK1 on mito-Ca2+ and mitochondrial morphology, apparently in a
      transport-independent manner. Miro overexpression mimics PINK1 loss-of-function
      effect, whereas inhibition of Miro or components of the ERMCS, or pharmacological
      modulation of ERMCS function, rescued PINK1 mutant phenotypes. Mito-Ca2+
      homeostasis is also altered in the LRRK2-G2019S model of PD and the PAR-1/MARK
      model of neurodegeneration, and genetic or pharmacological restoration of mito
      Ca2+ level is beneficial in these models. Our results highlight the importance of
      mito-Ca2+ homeostasis maintained by Miro and the ERMCS to mitochondrial
      physiology and neuronal integrity. Targeting this mito-Ca2+ homeostasis pathway
      holds promise for a therapeutic strategy for neurodegenerative diseases.

PMID- 30185554
TI  - Structure of the membrane proximal external region of HIV-1 envelope
      glycoprotein.
AB  - The membrane-proximal external region (MPER) of the HIV-1 envelope glycoprotein
      (Env) bears epitopes of broadly neutralizing antibodies (bnAbs) from infected
      individuals; it is thus a potential vaccine target. We report an NMR structure of
      the MPER and its adjacent transmembrane domain in bicelles that mimic a lipid
      bilayer membrane. The MPER lies largely outside the lipid bilayer. It folds into
      a threefold cluster, stabilized mainly by conserved hydrophobic residues and
      potentially by interaction with phospholipid headgroups. Antigenic analysis and
      comparison with published images from electron cryotomography of HIV-1 Env on the
      virion surface suggest that the structure may represent a prefusion conformation
      of the MPER, distinct from the fusion-intermediate state targeted by several well
      studied bnAbs. Very slow bnAb binding indicates that infrequent fluctuations of
      the MPER structure give these antibodies occasional access to alternative
      conformations of MPER epitopes. Mutations in the MPER not only impede membrane
      fusion but also influence presentation of bnAb epitopes in other regions. These
      results suggest strategies for developing MPER-based vaccine candidates.

PMID- 30185555
TI  - Clinical and veterinary trypanocidal benzoxaboroles target CPSF3.
AB  - African trypanosomes cause lethal and neglected tropical diseases, known as
      sleeping sickness in humans and nagana in animals. Current therapies are limited,
      but fortunately, promising therapies are in advanced clinical and veterinary
      development, including acoziborole (AN5568 or SCYX-7158) and AN11736,
      respectively. These benzoxaboroles will likely be key to the World Health
      Organization's target of disease control by 2030. Their mode of action was
      previously unknown. We have developed a high-coverage overexpression library and
      use it here to explore drug mode of action in Trypanosoma brucei Initially, an
      inhibitor with a known target was used to select for drug resistance and to test
      massive parallel library screening and genome-wide mapping; this effectively
      identified the known target and validated the approach. Subsequently, the
      overexpression screening approach was used to identify the target of the
      benzoxaboroles, Cleavage and Polyadenylation Specificity Factor 3 (CPSF3,
      Tb927.4.1340). We validated the CPSF3 endonuclease as the target, using
      independent overexpression strains. Knockdown provided genetic validation of
      CPSF3 as essential, and GFP tagging confirmed the expected nuclear localization.
      Molecular docking and CRISPR-Cas9-based editing demonstrated how acoziborole can
      specifically block the active site and mRNA processing by parasite, but not host
      CPSF3. Thus, our findings provide both genetic and chemical validation for CPSF3
      as an important drug target in trypanosomes and reveal inhibition of mRNA
      maturation as the mode of action of the trypanocidal benzoxaboroles.
      Understanding the mechanism of action of benzoxaborole-based therapies can assist
      development of improved therapies, as well as the prediction and monitoring of
      resistance, if or when it arises.

PMID- 30185557
TI  - Metal-insulator-transition engineering by modulation tilt-control in perovskite
      nickelates for room temperature optical switching.
AB  - In transition metal perovskites ABO3, the physical properties are largely driven
      by the rotations of the BO6 octahedra, which can be tuned in thin films through
      strain and dimensionality control. However, both approaches have fundamental and
      practical limitations due to discrete and indirect variations in bond angles,
      bond lengths, and film symmetry by using commercially available substrates. Here,
      we introduce modulation tilt control as an approach to tune the ground state of
      perovskite oxide thin films by acting explicitly on the oxygen octahedra rotation
      modes-that is, directly on the bond angles. By intercalating the prototype SmNiO3
      target material with a tilt-control layer, we cause the system to change the
      natural amplitude of a given rotation mode without affecting the interactions. In
      contrast to strain and dimensionality engineering, our method enables a
      continuous fine-tuning of the materials' properties. This is achieved through two
      independent adjustable parameters: the nature of the tilt-control material
      (through its symmetry, elastic constants, and oxygen rotation angles), and the
      relative thicknesses of the target and tilt-control materials. As a result, a
      magnetic and electronic phase diagram can be obtained, normally only accessible
      by A-site element substitution, within the single SmNiO3 compound. With this
      unique approach, we successfully adjusted the metal-insulator transition (MIT) to
      room temperature to fulfill the desired conditions for optical switching
      applications.

PMID- 30185556
TI  - Phylogenetic approach to recover integration dates of latent HIV sequences within
      host.
AB  - Given that HIV evolution and latent reservoir establishment occur continually
      within-host, and that latently infected cells can persist long-term, the HIV
      reservoir should comprise a genetically heterogeneous archive recapitulating
      within-host HIV evolution. However, this has yet to be conclusively demonstrated,
      in part due to the challenges of reconstructing within-host reservoir
      establishment dynamics over long timescales. We developed a phylogenetic
      framework to reconstruct the integration dates of individual latent HIV lineages.
      The framework first involves inference and rooting of a maximum-likelihood
      phylogeny relating plasma HIV RNA sequences serially sampled before the
      initiation of suppressive antiretroviral therapy, along with putative latent
      sequences sampled thereafter. A linear model relating root-to-tip distances of
      plasma HIV RNA sequences to their sampling dates is used to convert root-to-tip
      distances of putative latent lineages to their establishment (integration) dates.
      Reconstruction of the ages of putative latent sequences sampled from chronically
      HIV-infected individuals up to 10 y following initiation of suppressive therapy
      revealed a genetically heterogeneous reservoir that recapitulated HIV's within
      host evolutionary history. Reservoir sequences were interspersed throughout
      multiple within-host lineages, with the oldest dating to >20 y before sampling;
      historic genetic bottleneck events were also recorded therein. Notably, plasma
      HIV RNA sequences isolated from a viremia blip in an individual receiving
      otherwise suppressive therapy were highly genetically diverse and spanned a 20-y
      age range, suggestive of spontaneous in vivo HIV reactivation from a large
      latently infected cell pool. Our framework for reservoir dating provides a
      potentially powerful addition to the HIV persistence research toolkit.

PMID- 30185558
TI  - ASCT1 (Slc1a4) transporter is a physiologic regulator of brain d-serine and
      neurodevelopment.
AB  - d-serine is a physiologic coagonist of NMDA receptors, but little is known about
      the regulation of its synthesis and synaptic turnover. The amino acid exchangers
      ASCT1 (Slc1a4) and ASCT2 (Slc1a5) are candidates for regulating d-serine levels.
      Using ASCT1 and ASCT2 KO mice, we report that ASCT1, rather than ASCT2, is a
      physiologic regulator of d-serine metabolism. ASCT1 is a major d-serine uptake
      system in astrocytes and can also export l-serine via heteroexchange, supplying
      neurons with the substrate for d-serine synthesis. ASCT1-KO mice display lower
      levels of brain d-serine along with higher levels of l-alanine, l-threonine, and
      glycine. Deletion of ASCT1 was associated with neurodevelopmental alterations
      including lower hippocampal and striatal volumes and changes in the expression of
      neurodevelopmental-relevant genes. Furthermore, ASCT1-KO mice exhibited deficits
      in motor function, spatial learning, and affective behavior, along with changes
      in the relative contributions of d-serine vs. glycine in mediating NMDA receptor
      activity. In vivo microdialysis demonstrated lower levels of extracellular d
      serine in ASCT1-KO mice, confirming altered d-serine metabolism. These
      alterations are reminiscent of some of the neurodevelopmental phenotypes
      exhibited by patients with ASCT1 mutations. ASCT1-KO mice provide a useful model
      for potential therapeutic interventions aimed at correcting the metabolic
      impairments in patients with ASCT1 mutations.

PMID- 30185559
TI  - Defective cortex glia plasma membrane structure underlies light-induced epilepsy
      in cpes mutants.
AB  - Seizures induced by visual stimulation (photosensitive epilepsy; PSE) represent a
      common type of epilepsy in humans, but the molecular mechanisms and genetic
      drivers underlying PSE remain unknown, and no good genetic animal models have
      been identified as yet. Here, we show an animal model of PSE, in Drosophila,
      owing to defective cortex glia. The cortex glial membranes are severely
      compromised in ceramide phosphoethanolamine synthase (cpes)-null mutants and fail
      to encapsulate the neuronal cell bodies in the Drosophila neuronal cortex.
      Expression of human sphingomyelin synthase 1, which synthesizes the closely
      related ceramide phosphocholine (sphingomyelin), rescues the cortex glial
      abnormalities and PSE, underscoring the evolutionarily conserved role of these
      lipids in glial membranes. Further, we show the compromise in plasma membrane
      structure that underlies the glial cell membrane collapse in cpes mutants and
      leads to the PSE phenotype.

PMID- 30185561
TI  - Insights into autophagosome biogenesis from structural and biochemical analyses
      of the ATG2A-WIPI4 complex.
AB  - Autophagy is an enigmatic cellular process in which double-membrane compartments,
      called "autophagosomes, form de novo adjacent to the endoplasmic reticulum (ER)
      and package cytoplasmic contents for delivery to lysosomes. Expansion of the
      precursor membrane phagophore requires autophagy-related 2 (ATG2), which
      localizes to the PI3P-enriched ER-phagophore junction. We combined single
      particle electron microscopy, chemical cross-linking coupled with mass
      spectrometry, and biochemical analyses to characterize human ATG2A in complex
      with the PI3P effector WIPI4. ATG2A is a rod-shaped protein that can bridge
      neighboring vesicles through interactions at each of its tips. WIPI4 binds to one
      of the tips, enabling the ATG2A-WIPI4 complex to tether a PI3P-containing vesicle
      to another PI3P-free vesicle. These data suggest that the ATG2A-WIPI4 complex
      mediates ER-phagophore association and/or tethers vesicles to the ER-phagophore
      junction, establishing the required organization for phagophore expansion via the
      transfer of lipid membranes from the ER and/or the vesicles to the phagophore.

PMID- 30185560
TI  - Genetic screen identifies adaptive aneuploidy as a key mediator of ER stress
      resistance in yeast.
AB  - The yeast genome becomes unstable during stress, which often results in adaptive
      aneuploidy, allowing rapid activation of protective mechanisms that restore
      cellular homeostasis. In this study, we performed a genetic screen in
      Saccharomyces cerevisiae to identify genome adaptations that confer resistance to
      tunicamycin-induced endoplasmic reticulum (ER) stress. Whole-genome sequencing of
      tunicamycin-resistant mutants revealed that ER stress resistance correlated
      significantly with gains of chromosomes II and XIII. We found that chromosome
      duplications allow adaptation of yeast cells to ER stress independently of the
      unfolded protein response, and that the gain of an extra copy of chromosome II
      alone is sufficient to induce protection from tunicamycin. Moreover, the
      protective effect of disomic chromosomes can be recapitulated by overexpression
      of several genes located on chromosome II. Among these genes, overexpression of
      UDP-N-acetylglucosamine-1-P transferase (ALG7), a subunit of the 20S proteasome
      (PRE7), and YBR085C-A induced tunicamycin resistance in wild-type cells, whereas
      deletion of all three genes completely reversed the tunicamycin-resistance
      phenotype. Together, our data demonstrate that aneuploidy plays a critical role
      in adaptation to ER stress by increasing the copy number of ER stress protective
      genes. While aneuploidy itself leads to proteotoxic stress, the gene-specific
      effects of chromosome II aneuploidy counteract the negative effect resulting in
      improved protein folding.

PMID- 30185562
TI  - Wetting controls of droplet formation in step emulsification.
AB  - The formation of droplets is ubiquitous in many natural and industrial processes
      and has reached an unprecedented level of control with the emergence of milli-
      and microfluidics. Although important insight into the mechanisms of droplet
      formation has been gained over the past decades, a sound understanding of the
      physics underlying this phenomenon and the effect of the fluid's flow and wetting
      properties on the droplet size and production rate is still missing, especially
      for the widely applied method of step emulsification. In this work, we elucidate
      the physical controls of microdroplet formation in step emulsification by using
      the wetting of fluidic channels as a tunable parameter to explore a broad set of
      emulsification conditions. With the help of high-speed measurements, we
      unequivocally show that the final droplet pinch-off is triggered by a Rayleigh
      Plateau-type instability. The droplet size, however, is not determined by the
      Rayleigh-Plateau breakup, but by the initial wetting regime, where the fluid's
      contact angle plays a crucial role. We develop a physical theory for the wetting
      process, which closely describes our experimental measurements without invoking
      any free fit parameter. Our theory predicts the initiation of the Rayleigh
      Plateau breakup and the transition from dripping to jetting as a function of the
      fluid's contact angle. Additionally, the theory solves the conundrum why there is
      a minimal contact angle of alpha = 2pi/3 = 120 degrees  for which droplets can
      form.

PMID- 30185564
TI  - Linking economic growth pathways and environmental sustainability by
      understanding development as alternate social-ecological regimes.
AB  - Scientists understand how global ecological degradation is occurring but not why
      it seems to be so difficult to reverse. We used national-level data and a
      mathematical model to provide an empirical test of the hypothesis that national
      economies display two distinct economic regimes that are maintained by self
      reinforcing feedbacks between natural resources and society. Our results not only
      support previous findings that two distinct groups exist, but also show that
      countries move toward one of these two different equilibrium points because of
      their different patterns of natural resource use and responses to population
      growth. At the less economically developed equilibrium point maintained by "green
      loop" feedbacks, human populations depend more directly on ecosystems for income.
      At the more economically developed equilibrium point maintained by "red-loop"
      feedbacks, nonecosystem services (e.g., technology, manufacturing, services)
      generate the majority of national gross domestic product (GDP), but increasing
      consumption of natural resources means that environmental impacts are higher and
      are often exported (via cross-scale feedbacks) to other countries. Feedbacks
      between income and population growth are pushing countries farther from
      sustainability. Our analysis shows that economic growth alone cannot lead to
      environmental sustainability and that current trajectories of resource use cannot
      be sustained without breaking feedback loops in national and international
      economies.

PMID- 30185563
TI  - Elimination of the error signal in the superior colliculus impairs saccade motor
      learning.
AB  - When movements become dysmetric, the resultant motor error induces a plastic
      change in the cerebellum to correct the movement, i.e., motor adaptation. Current
      evidence suggests that the error signal to the cerebellum is delivered by complex
      spikes originating in the inferior olive (IO). To prove a causal link between the
      IO error signal and motor adaptation, several studies blocked the IO, which,
      unfortunately, affected not only the adaptation but also the movement itself. We
      avoided this confound by inactivating the source of an error signal to the IO.
      Several studies implicate the superior colliculus (SC) as the source of the error
      signal to the IO for saccade adaptation. When we inactivated the SC, the metrics
      of the saccade to be adapted were unchanged, but saccade adaptation was impaired.
      Thus, an intact rostral SC is necessary for saccade adaptation. Our data provide
      experimental evidence for the cerebellar learning theory that requires an error
      signal to drive motor adaptation.

PMID- 30185565
TI  - Glioma-derived cancer stem cells are hypersensitive to proteasomal inhibition.

PMID- 30185566
TI  - Longitudinal body weight and sputum conversion in patients with tuberculosis,
      Southwest Ethiopia: a retrospective follow-up study.
AB  - OBJECTIVES: To describe the association between change in body weight and sputum
      smear conversion and to identify factors linked with body weight and sputum smear
      conversion in Jimma University Specialized Hospital, Southwest Ethiopia. DESIGN:
      A retrospective follow-up study. SETTING: Teaching hospital in Southwest
      Ethiopia. PARTICIPANTS: A total of 450 patients with tuberculosis (TB) were
      included in the follow-up between 2011 and 2013. MAIN OUTCOME MEASURES: The
      association between body weight and sputum conversion was measured using joint
      modelling. RESULTS: The association between change in body weight and change in
      sputum conversion was -0.698 (p<0.001). A strong inverse association between
      change in body weight and change in sputum conversion was observed. The study
      variables sex, age, type of TB, HIV status, dose of anti-TB drug and length of
      enrolment to TB treatment were significantly associated with change in body
      weight of patients with TB. The study variables age, type of TB, dose of anti-TB
      drug and length of enrolment were significantly associated with change in sputum
      status of patients with TB. CONCLUSIONS: Among patients with TB who were on anti
      TB treatment, increase in body weight and positive sputum status were inversely
      related over time. TB prevention and control strategies should give emphasis on
      factors such as female sex, older age, non-pulmonary positive type of TB, HIV
      positive, lower dose of anti-TB drug and length of enrolment to TB treatment
      during monitoring of trends in body weight and sputum status.

PMID- 30185567
TI  - Perceptions of cigarette pack inserts promoting cessation and dissuasive
      cigarettes among young adult smokers in the UK: a cross-sectional online survey.
AB  - OBJECTIVES: To explore young adult smokers' perceptions of cigarette pack inserts
      promoting cessation and cigarettes designed to be dissuasive. DESIGN: Cross
      sectional online survey. SETTING: UK. PARTICIPANTS: The final sample was 1766
      young adult smokers, with 50.3% male and 71.6% white British. To meet the
      inclusion criteria, participants had to be 16-34 years old and smoke factory-made
      cigarettes. PRIMARY AND SECONDARY OUTCOME MEASURES: Salience of inserts,
      perceptions of inserts as information provision, perceptions of inserts on
      quitting, support for inserts and perceived appeal, harm and trial of three
      cigarettes (a standard cigarette, a standard cigarette displaying the warning
      'Smoking kills' and a green cigarette). RESULTS: Half the sample indicated that
      they would read inserts with three-fifths indicating that they are a good way to
      provide information about quitting (61%). Just over half indicated that inserts
      would make them think more about quitting (53%), help if they decided to quit
      (52%), are an effective way of encouraging smokers to quit (53%) and supported
      having them in all packs (55%). Participants who smoked factory-made cigarettes
      and other tobacco products (compared with exclusive factory-made cigarette
      smokers), had made a quit attempt within the last 6 months (compared with those
      that had never made a quit attempt) or were likely to make a successful quit
      attempt in the next 6 months (compared with those unlikely to make a quit attempt
      in the next 6 months) were more likely to indicate that inserts could assist with
      cessation. Multivariable logistic regression modelling suggested that compared
      with the standard cigarette, the cigarette with warning (adjusted OR=17.71; 95%
      CI 13.75 to 22.80) and green cigarette (adjusted OR=30.88; 95% CI 23.98 to 39.76)
      were much less desirable (less appealing, more harmful and less likely to be
      tried). CONCLUSIONS: Inserts and dissuasive cigarettes offer policy makers
      additional ways of using the pack to reduce smoking.

PMID- 30185568
TI  - Association between Hashimoto's thyroiditis and cholelithiasis: a retrospective
      cohort study in Taiwan.
AB  - OBJECTIVE: To investigate the relation of Hashimoto's thyroiditis (HT) to
      cholelithiasis and cholecystectomy in a retrospective population-based study.
      SETTING: Cohort study. PARTICIPANTS: We identified 1268 patients aged >=20 years
      with HT between 2000 and 2010 as the study cohort. PRIMARY AND SECONDARY OUTCOME
      MEASURES: Patients without HT were randomly selected from a database and
      propensity-matched with the study cohort at a 1:4 ratio according to age, sex,
      comorbidities and year of the index date to measure the incidence of
      cholelithiasis and cholecystectomy. RESULTS: The cumulative incidence of
      cholelithiasis was higher in the HT cohort than that in the non-HT cohort (log
      rank test, p<0.001), with a 1.91-fold higher risk of choleithiasis (95% CI 1.58
      to 2.33) after adjustment for comorbidities. The age-specific relative risk of
      cholelithiasis in the HT cohort was higher than that in the non-HT cohort for
      patients aged >=50 years (adjusted HR (aHR)=2.59, 95% CI 1.33 to 5.03). The sex
      specific relative risk of cholelithiasis in the HT cohort was higher than that in
      the non-HT cohort for women (aHR=1.99, 95% CI 1.63 to 2.44). Compared with those
      in the non-HT cohort, patients with HT without (aHR=1.95, 95% CI 1.53 to 2.49)
      and with (aHR=1.94, 95% CI 1.51 to 2.49) thyroxine treatment were associated with
      a higher risk of cholelithiasis. Compared with those in the non-HT cohort,
      patients with HT had a higher risk of cholecystectomy (aHR=1.28, 95% CI 1.02 to
      1.61). CONCLUSIONS: Inability to obtain information on several potential
      confounding factors and misclassification of important covariates are the major
      limitations of the study. Our study indicates HT per se was associated with the
      development of cholelithiasis, which has been validated by the association
      between cholecystectomy and HT. Surveys and health education on cholelithiasis in
      women aged >=50 years with HT should be considered by clinicians, and further
      prospective research should be done on this topic.

PMID- 30185569
TI  - Factors hindering the adherence to clinical practice guideline for diabetes
      mellitus in the Palestinian primary healthcare clinics: a qualitative study.
AB  - OBJECTIVE: Despite a high number of the internationally produced and implemented
      clinical guidelines, the adherence with them is still low in healthcare. This
      study aimed at exploring the perspectives and experiences of senior doctors and
      nurses towards the barriers of adherence to diabetes guideline. SETTING: The
      Palestinian Primary Health Care-Ministry of Health (PHC-MoH) and Primary Health
      Care-United Nations Relief and Works Agency for Palestine Refugees in the Near
      East (PHC- UNRWA) in Gaza Strip. PARTICIPANTS: Individual face-to-face in-depth
      interviews were conducted with 20 senior doctors and nurses who were purposefully
      selected. METHODS: Qualitative design was employed using the theoretical
      framework by Cabana et al to develop an interview guide. Semi-structural and
      audio-recorded interviews were conducted. Data were transcribed verbatim and
      thematically analysed. RESULTS: The key theme barriers identified by participants
      that emerged from the analysed data were in regard of the PHC-MoH lack
      reimbursement, lack of resources and lack of the guideline trustworthiness, and
      in regard of PHC-UNRWA the time constraints and the lack of the guideline
      trustworthiness. The two key subthemes elicited from the qualitative analysis
      were the outdated guideline and lack of auditing and feedback. CONCLUSION: The
      analysis identified a wide range of barriers against the adherence to diabetes
      guideline within the PHC-MoH and PHC-UNRWA. The environmental-related and
      guideline-related barriers were the most prominent factors influencing the
      guideline adherence. Our study can inform the policy makers and senior managers
      to develop a tailored interventions that can target the elicited barriers through
      a multifaceted implementation strategy.

PMID- 30185570
TI  - What factors influence older people's intention to enrol in nursing homes? A
      cross-sectional observational study in Shanghai, China.
AB  - OBJECTIVES: Given the increasing need of long-term care and the low occupancy
      rate of nursing homes in Shanghai, this study attempts to explore what factors
      influence older people's intention to enrol in nursing homes. DESIGN: A cross
      sectional observational study based on the theory of reasoned action was
      conducted. Survey data were collected from subjects during face-to-face
      interviews. Structural equation modelling was employed for data analysis.
      SETTING: This study was conducted in six community health service centres in
      Shanghai, China. Two service centres were selected in urban, suburban and rural
      areas, respectively. PARTICIPANTS: A total of 641 Shanghai residents aged over 60
      were surveyed. RESULTS: Structural equation modelling analysis showed that the
      research model fits the data well (chi2/df=2.948, Comparative Fit Index=0.972 and
      root mean squared error of approximation =0.055). Attitude (beta=0.41, p<0.01),
      subjective norm (beta=0.28, p<0.01) and value-added service (beta=0.16, p<0.01)
      were directly associated with enrolment intention, explaining 32% of variance in
      intention. Attitude was significantly influenced by loneliness (beta=-0.08,
      p<0.05), self-efficacy (beta=0.32, p<0.01) and stigma (beta=-0.24, p<0.01), while
      subjective norm was significantly influenced by life satisfaction (beta=-0.15,
      p<0.01) and stigma (beta=-0.43, p<0.01). CONCLUSIONS: This study advances
      knowledge regarding the influencing factors of older people's intention to enrol
      in nursing homes. It suggests that Chinese older persons' perceived stigma has
      the strongest indirect effect on their intention to enrol in nursing homes. This
      is unique to the Chinese context and has practical implications for eldercare in
      China and other Asian countries with similar sociocultural contexts.

PMID- 30185571
TI  - Association of guideline and policy changes with incidence of lifestyle advice
      and treatment for uncomplicated mild hypertension in primary care: a longitudinal
      cohort study in the Clinical Practice Research Datalink.
AB  - OBJECTIVES: Evidence to support initiation of pharmacological treatment in
      patients with uncomplicated (low risk) mild hypertension is inconclusive. As
      such, clinical guidelines are contradictory and healthcare policy has changed
      regularly. The aim of this study was to determine the incidence of lifestyle
      advice and drug therapy in this population and whether secular trends were
      associated with policy changes. DESIGN: Longitudinal cohort study. SETTING:
      Primary care practices contributing to the Clinical Practice Research Datalink in
      England. PARTICIPANTS: Data were extracted from the linked electronic health
      records of patients aged 18-74 years, with stage 1 hypertension (blood pressure
      between 140/90 and 159/99 mm Hg), no cardiovascular disease (CVD) risk factors
      and no treatment, from 1998 to 2015. Patients exited if follow-up records became
      unavailable, they progressed to stage 2 hypertension, developed a CVD risk factor
      or received lifestyle advice/treatment. PRIMARY OUTCOME MEASURES: The association
      between policy changes and incidence of lifestyle advice or treatment, examined
      using an interrupted time-series analysis. RESULTS: A total of 108 843 patients
      were defined as having uncomplicated mild hypertension (mean age 51.9+/-12.9
      years, 60.0% female). Patientsspent a median 2.6 years (IQR 0.9-5.5) in the
      study, after which 12.2% (95% CI 12.0% to 12.4%) were given lifestyle advice,
      29.9% (95% CI 29.7% to 30.2%) were prescribed medication and 19.4% (95% CI 19.2%
      to 19.6%) were given both. The introduction of the quality outcomes framework
      (QOF) and subsequent changes to QOF indicators were followed by significant
      increases in the incidence of lifestyle advice. Treatment prescriptions decreased
      slightly over time, but were not associated with policy changes. CONCLUSIONS:
      Despite secular trends that accord with UK guidance, many patients are still
      prescribed treatment for mild hypertension. Adequately powered studies are needed
      to determine if this is appropriate.

PMID- 30185572
TI  - Prevalence of age-specific and sex-specific overweight and obesity in Ontario and
      Quebec, Canada: a cross-sectional study using direct measures of height and
      weight.
AB  - OBJECTIVE: To evaluate whether combining three cycles of the Canadian Health
      Measures Survey (CHMS) produces provincially representative and valid estimates
      of overweight and obesity in Ontario and Quebec. SETTING: An ongoing, nationally
      representative health survey in Canada, with data released every 2 years.
      Objective measures of height and weight were taken at mobile examination centres
      located within 100 km of participants' residences. To increase sample size, we
      combined three cycles completed during 2007-2013. PARTICIPANTS: 5740 Ontario
      residents and 3980 Quebec residents aged 6-79, with birth dates and directly
      measured height and weight recorded in the CHMS. Pregnant females were excluded.
      Sociodemographic characteristics of the Ontario and Quebec portions of the CHMS
      appeared similar to characteristics from the 2006 Canada Census. PRIMARY OUTCOME
      MEASURES: Objectively measured overweight and obesity prevalence overall and
      among males and females in the following age groups: 6-11, 12-19, 20-39, 40-59
      and 60-79. We compared these with provincially representative and objectively
      measured estimates from the 2015 Canadian Community Health Survey (CCHS)
      Nutrition. RESULTS: 57.1% (95% CI 52.8% to 61.4%) of Ontarians were classified
      overweight or obese and 24.0% (95% CI 20.3% to 27.6%) obese, while Quebec's
      corresponding percentages were 56.2% (95% CI 51.3% to 61.1%) and 24.4% (95% CI
      20.6% to 28.3%). Generally, overweight and obesity combined was higher in older
      age groups and males. Comparisons with the CCHS-Nutrition did not yield
      unexplainable differences between surveys. CONCLUSIONS: Combining three CHMS
      cycles can produce estimates of overweight and obesity in populations
      representative of Ontario and Quebec. As new CHMS data are collected, these
      estimates can be updated and used to evaluate trends.

PMID- 30185573
TI  - Investigating equalisation of health inequalities during adolescence in four low
      income and middle-income countries: an analysis of the Young Lives cohort study.
AB  - OBJECTIVE: To investigate if socioeconomic gradients in health reduce during
      adolescence (the equalisation hypothesis) in four low-income and middle-income
      countries (LMIC). SETTING: Analysis of the Young Lives Study cohorts in Ethiopia,
      Peru, Vietnam and India. PARTICIPANTS: A total of 3395 participants (across the
      four cohorts) aged 6-10 years at enrolment and followed up for 11 years. OUTCOMES
      MEASURED: Change in income-related health inequalities from mid-childhood to late
      adolescence. Socioeconomic status was determined by wealth index quartile. The
      health indicators included were self-reported health, injuries in the previous 4
      years, presence of long-term health problems, low mood, alcohol use,
      overweight/obesity, thinness and stunting. The relative risk of each adverse
      health outcome between highest and lowest wealth index quartile were compared
      across four waves of the study within each country. RESULTS: We found steep
      socioeconomic gradients across multiple health indicators in all four countries.
      Socioeconomic gradients remained similar across all waves of the study, with no
      significant decrease during adolescence. CONCLUSION: We found no consistent
      evidence of equalisation for income-related health inequalities in youth in these
      LMIC. Socioeconomic gradients for health in these cohorts appear to persist and
      be equally damaging across the early life course and during adolescence.

PMID- 30185574
TI  - Demographic and clinical factors associated with different antidepressant
      treatments: a retrospective cohort study design in a UK psychiatric healthcare
      setting.
AB  - OBJECTIVE: To investigate the demographic and clinical factors associated with
      antidepressant use for depressive disorder in a psychiatric healthcare setting
      using a retrospective cohort study design. SETTING: Data were extracted from a de
      identified data resource sourced from the electronic health records of a London
      mental health service. Relative risk ratios (RRRs) were obtained from multinomial
      logistic regression analysis to ascertain the probability of receiving common
      antidepressant treatments relative to sertraline. PARTICIPANTS: Patients were
      included if they received mental healthcare and a diagnosis of depression with
      antidepressant treatment between March and August 2015 and exposures were
      measured over the preceding 12 months. RESULTS: Older age was associated with
      increased use of all antidepressants compared with sertraline, except for
      negative associations with fluoxetine (RRR 0.98; 95% CI 0.96 to 0.98) and a
      combination of two selective serotonin reuptake inhibitors (SSRIs) (0.98; 95% CI
      0.96 to 0.99), and no significant association with escitalopram. Male gender was
      associated with increased use of mirtazapine compared with sertraline (2.57; 95%
      CI 1.85 to 3.57). Previous antidepressant, antipsychotic and mood stabiliser use
      were associated with newer antidepressant use (ie, selective norepinephrine
      reuptake inhibitors, mirtazapine or a combination of both), while affective
      symptoms were associated with reduced use of citalopram (0.58; 95% CI 0.27 to
      0.83) and fluoxetine (0.42; 95% CI 0.22 to 0.72) and somatic symptoms were
      associated with increased use of mirtazapine (1.60; 95% CI 1.00 to 2.75) relative
      to sertraline. In patients older than 25 years, past benzodiazepine use was
      associated with a combination of SSRIs (2.97; 95% CI 1.32 to 6.68), mirtazapine
      (1.94; 95% CI 1.20 to 3.16) and venlafaxine (1.87; 95% CI 1.04 to 3.34), while
      past suicide attempts were associated with increased use of fluoxetine (2.06; 95%
      CI 1.10 to 3.87) relative to sertraline. CONCLUSION: There were several factors
      associated with different antidepressant receipt in psychiatric healthcare. In
      patients aged >25, those on fluoxetine were more likely to have past suicide
      attempt, while past use of antidepressant and non-antidepressant use was also
      associated with use of new generation antidepressants, potentially reflecting
      perceived treatment resistance.

PMID- 30185575
TI  - Study protocol for a single-blind, randomised controlled, non-inferiority trial
      of internet-based versus face-to-face cognitive behaviour therapy for obsessive
      compulsive disorder.
AB  - INTRODUCTION: Expert guidelines recommend cognitive-behavioural therapy (CBT) as
      a first-line treatment for obsessive-compulsive disorder (OCD), but the majority
      of patients with OCD do not have access to CBT. Internet-delivered CBT (ICBT) has
      the potential to make this evidence-based treatment more accessible while
      requiring less therapist time than traditional face-to-face (f2f) CBT. Data from
      six clinical trials suggest that ICBT for OCD is both efficacious and cost
      effective, but whether ICBT is non-inferior to traditional f2f CBT for OCD is yet
      unknown. METHODS AND ANALYSIS: A single-blind, randomised, controlled, non
      inferiority trial comparing therapist-guided ICBT, unguided ICBT and individual
      (f2f) CBT for adult OCD patients. The primary objective is to investigate whether
      ICBT is non-inferior to gold standard f2f CBT. Secondary objectives are to
      investigate if ICBT is equally effective when delivered unguided, to establish
      the cost-effectiveness of ICBT and to investigate if the treatment outcome
      differs between self-referred and clinically referred patients. Participants will
      be recruited at two specialist OCD clinics in Stockholm and also through online
      self-referral. Participants will be randomised to one of three treatment
      conditions: F2f CBT, ICBT with therapist support or unguided ICBT. The total
      number of participants will be 120, and masked assessments will be administered
      at baseline, biweekly during treatment, at post-treatment and at 3-month and 12
      month follow-ups. The main outcome measure is the clinician-rated Yale-Brown
      Obsessive Compulsive Scale (Y-BOCS) at 3-month follow-up. The margin of non
      inferiority is set to 3 points on the Y-BOCS using a 90% CI. ETHICS AND
      DISSEMINATION: The study has been approved by the Regional Ethics Board of
      Stockholm (REPN 2015/1099-31/2) and registered at Clinicaltrials.gov
      (NCT02541968). The study will be reported in accordance with the Consolidated
      Standards of Reporting Trials statement for non-pharmacological trials. The
      results will be published in peer-reviewed academic journals and disseminated to
      patient organisations and media. TRIAL REGISTRATION NUMBER: NCT02541968; Pre
      results.

PMID- 30185576
TI  - Emergency medical dispatch recognition, clinical intervention and outcome of
      patients in traumatic cardiac arrest from major trauma: an observational study.
AB  - OBJECTIVES: The aim of this study is to describe the demographics of reported
      traumatic cardiac arrest (TCA) victims, prehospital resuscitation and survival to
      hospital rate. SETTING: Helicopter Emergency Medical Service (HEMS) in south-east
      England, covering a resident population of 4.5 million and a transient population
      of up to 8 million people. PARTICIPANTS: Patients reported on the initial 999
      call to be in suspected traumatic cardiac arrest between 1 July 2016 and 31
      December 2016 within the trust's geographical region were identified. The
      inclusion criteria were all cases of reported TCA on receipt of the initial
      emergency call. Patients were subsequently excluded if a medical cause of cardiac
      arrest was suspected. OUTCOME MEASURES: Patient records were analysed for actual
      presence of cardiac arrest, prehospital resuscitation procedures undertaken and
      for survival to hospital rates. RESULTS: 112 patients were reported to be in TCA
      on receipt of the 999/112 call. 51 (46%) were found not to be in TCA on arrival
      of emergency medical services. Of the 'not in TCA cohort', 34 (67%) received at
      least one advanced prehospital medical intervention (defined as emergency
      anaesthesia, thoracostomy, blood product transfusion or resuscitative
      thoracotomy). Of the 61 patients in actual TCA, 10 (16%) achieved return-of
      spontaneous circulation. In 45 (88%) patients, the HEMS team escorted the patient
      to hospital. CONCLUSION: A significant proportion of patients reported to be in
      TCA on receipt of the emergency call are not in actual cardiac arrest but are
      critically unwell requiring advanced prehospital medical intervention. Early
      activation of an enhanced care team to a reported TCA call allows appropriate
      advanced resuscitation. Further research is warranted to determine which
      interventions contribute to improved TCA survival.

PMID- 30185578
TI  - Spatio - temporal modelling assessing the burden of malaria in affected low and
      middle-income countries: a scoping review.
AB  - INTRODUCTION: Spatio - temporal modelling of malaria has proven to be a valuable
      tool for forecasting as well as control and elimination activities. This has been
      triggered by an increasing availability of spatially indexed data, enabling not
      only the characterisation of malaria at macrospatial and microspatial levels but
      also the development of geospatial techniques and tools that enable health policy
      planners to use these available data more effectively. However, there has been
      little synthesis regarding the variety of spatio - temporal approaches employed,
      covariates employed and 'best practice' type recommendations to guide future
      modelling decisions. This review will seek to summarise available evidence on the
      current state of spatio - temporal modelling approaches that have been employed
      in malaria modelling in low and middle-income countries within malaria
      transmission limits, so as to guide future modelling decisions. METHODS AND
      ANALYSIS: A comprehensive search for articles published from January 1968 to
      April 2018 will be conducted using of the following electronic databases: PubMed,
      Web of Science, JSTOR, Cochrane CENTRAL via Wiley, Academic Search Complete via
      EBSCOhost, MasterFILE Premier via EBSCOhost, CINAHL via EBSCOhost, MEDLINE via
      EBSCOhost and Google Scholar. Relevant grey literature sources such as
      unpublished reports, conference proceedings and dissertations will also be
      incorporated in the search. Two reviewers will independently conduct the title
      screening, abstract screening and, thereafter, a full-text review of all
      potentially eligible articles. Preferred Reporting Items for Systematic Reviews
      and Meta-Analysis Protocols guidelines will be used as the standard reporting
      format. A qualitative thematic analysis will be used to group and evaluate
      selected studies around their aim, spatio - temporal methodology employed,
      covariates used and model validation techniques. ETHICS AND DISSEMINATION:
      Ethical approval is not applicable to this study. The results will be
      disseminated through a peer-reviewed journal and presented in conferences related
      to malaria and spatial epidemiology. PROSPERO REGISTRATION NUMBER:
      CRD42017076427.

PMID- 30185577
TI  - Identifying important health system factors that influence primary care
      practitioners' referrals for cancer suspicion: a European cross-sectional survey.
AB  - OBJECTIVES: Cancer survival and stage of disease at diagnosis and treatment vary
      widely across Europe. These differences may be partly due to variations in access
      to investigations and specialists. However, evidence to explain how different
      national health systems influence primary care practitioners' (PCPs') referral
      decisions is lacking.This study analyses health system factors potentially
      influencing PCPs' referral decision-making when consulting with patients who may
      have cancer, and how these vary between European countries. DESIGN: Based on a
      content-validity consensus, a list of 45 items relating to a PCP's decisions to
      refer patients with potential cancer symptoms for further investigation was
      reduced to 20 items. An online questionnaire with the 20 items was answered by
      PCPs on a five-point Likert scale, indicating how much each item affected their
      own decision-making in patients that could have cancer. An exploratory factor
      analysis identified the factors underlying PCPs' referral decision-making.
      SETTING: A primary care study; 25 participating centres in 20 European countries.
      PARTICIPANTS: 1830 PCPs completed the survey. The median response rate for
      participating centres was 20.7%. OUTCOME MEASURES: The factors derived from items
      related to PCPs' referral decision-making. Mean factor scores were produced for
      each country, allowing comparisons. RESULTS: Factor analysis identified five
      underlying factors: PCPs' ability to refer; degree of direct patient access to
      secondary care; PCPs' perceptions of being under pressure; expectations of PCPs'
      role; and extent to which PCPs believe that quality comes before cost in their
      health systems. These accounted for 47.4% of the observed variance between
      individual responses. CONCLUSIONS: Five healthcare system factors influencing
      PCPs' referral decision-making in 20 European countries were identified. The
      factors varied considerably between European countries. Knowledge of these
      factors could assist development of health service policies to produce better
      cancer outcomes, and inform future research to compare national cancer diagnostic
      pathways and outcomes.

PMID- 30185579
TI  - Electronic healthcare databases in Europe: descriptive analysis of
      characteristics and potential for use in medicines regulation.
AB  - OBJECTIVE: Electronic healthcare databases (EHDs) are useful tools for drug
      development and safety evaluation but their heterogeneity of structure, validity
      and access across Europe complicates the conduct of multidatabase studies. In
      this paper, we provide insight into available EHDs to support regulatory
      decisions on medicines. METHODS: EHDs were identified from publicly available
      information from the European Network of Centres for Pharmacoepidemiology and
      Pharmacovigilance resources database, textbooks and web-based searches. Databases
      were selected using criteria related to accessibility, longitudinal dimension,
      recording of exposure and outcomes, and generalisability. Extracted information
      was verified with the database owners. RESULTS: A total of 34 EHDs were selected
      after applying key criteria relevant for regulatory purposes. The most
      represented regions were Northern, Central and Western Europe. The most frequent
      types of data source were electronic medical records (44.1%) and record linkage
      systems (29.4%). The median number of patients registered in the 34 data sources
      was 5 million (range 0.07-15 million) while the median time covered by a database
      was 18.5 years. Paediatric patients were included in 32 databases (94%).
      Completeness of information on drug exposure was variable. Published validation
      studies were found for only 17 databases (50%). Some level of access exists for
      25 databases (73.5%), and 23 databases (67.6%) can be linked through a personal
      identification number to other databases with parent-child linkage possible in 7
      (21%) databases. Eight databases (23.5%) were already transformed or were in the
      process of being transformed into a common data model that could facilitate
      multidatabase studies. CONCLUSION: A Few European databases meet minimal
      regulatory requirements and are readily available to be used in a regulatory
      context. Accessibility and validity information of the included information needs
      to be improved. This study confirmed the fragmentation, heterogeneity and lack of
      transparency existing in many European EHDs.

PMID- 30185580
TI  - Relative importance of informational items in participant information leaflets
      for trials: a Q-methodology approach.
AB  - OBJECTIVES: To identify which information items potential participants and
      research nurses rank as the most important, and the reasons for this, when
      considering participation in a randomised controlled trial. DESIGN: Q-methodology
      approach alongside a think-aloud process. Using a vignette outlining a
      hypothetical trial, participants were asked to rank statements about
      informational items usually included in a participant information leaflet (PIL)
      on a Q-grid, while undertaking a real-time think-aloud process to elicit the
      underpinning decision processes. Analysis of quantitative data was conducted
      using descriptive statistics and qualitative data was coded using content
      analysis. PARTICIPANTS: 20 participants (10 potential trial participants and 10
      research nurses). SETTING: UK-based participants. RESULTS: Ten research nurses
      and 10 potential trial participants provided data for the study. Both stakeholder
      groups ranked similar statements in their top three most important statements,
      with 'What are the possible disadvantages and risks of taking part?' featuring in
      both. However, considerable variability existed between the groups with regard to
      their ranking of statements of least importance. Participants identified that
      sufficient information to make a decision was secured using around 14 items.
      Participants also identified other items of importance not routinely included in
      PILs. CONCLUSIONS: This study has provided a unique insight into how and why
      different trial stakeholder groups rank informational items currently contained
      within PILs. These results have implications for those developing future PILs and
      those who develop guidance on their content; PILs should focus most on the
      information items that potential trial participants want and need to make an
      informed choice about trial participation.

PMID- 30185581
TI  - Perspectives on involvement in the peer-review process: surveys of patient and
      public reviewers at two journals.
AB  - OBJECTIVE: In 2014/2015, The BMJ and Research Involvement and Engagement (RIE)
      became the first journals to routinely include patients and the public in the
      peer review process of journal articles. This survey explores the perspectives
      and early experiences of these reviewers. DESIGN: A cross-sectional survey.
      SETTING AND PARTICIPANTS: Patient and public reviewers for The BMJ and RIE who
      have been invited to review. RESULTS: The response rate was 69% (157/227) for
      those who had previously reviewed and 31% (67/217) for those who had not yet
      reviewed. Reviewers described being motivated to review by the opportunity to
      include the patient voice in the research process, influence the quality of the
      biomedical literature and ensure it meets the needs of patients. Of the 157 who
      had reviewed, 127 (81%) would recommend being a reviewer to other patients and
      carers. 144 (92%) thought more journals should adopt patient and public review.
      Few reviewers (16/224, 7%) reported concerns about doing open review. Annual
      acknowledgement on the journals' websites was welcomed as was free access to
      journal information. Participants were keen to have access to more online
      resources and training to improve their reviewing skills. Suggestions on how to
      improve the reviewing experience included: allowing more time to review; better
      and more frequent communication; a more user-friendly process; improving guidance
      on how to review including videos; improving the matching of papers to reviewers'
      experience; providing more varied sample reviews and brief feedback on the
      usefulness of reviews; developing a sense of community among reviewers; and
      publicising of the contribution that patient and public review brings.
      CONCLUSIONS: Patient and public reviewers shared practical ideas to improve the
      reviewing experience and these will be reviewed to enhance the guidance and
      support given to them.

PMID- 30185582
TI  - Prevalence and identification of anxiety disorders in pregnancy: the diagnostic
      accuracy of the two-item Generalised Anxiety Disorder scale (GAD-2).
AB  - OBJECTIVE: To estimate the population prevalence of anxiety disorders during
      pregnancy and investigate the diagnostic accuracy of the two-item Generalised
      Anxiety Disorder scale (GAD-2) for a) GAD and b) any anxiety disorder. DESIGN:
      Cross-sectional survey using a stratified sampling design. Sampling weights were
      used in the analysis to adjust for the bias introduced by the stratified
      sampling. SETTING: Inner-city maternity service, South London. PARTICIPANTS: 545
      pregnant women were interviewed after their first antenatal appointment; 528
      provided answers on the GAD-2 questions. MAIN OUTCOME MEASURES: Diagnosis
      generated by the Structured Clinical Interview for Diagnostic and Statistical
      Manual of Mental Disorders, 4th edition (SCID). RESULTS: Population prevalence of
      anxiety disorders was 17% (95% CI 12% to 21%): 5% (95% CI 3% to 6%) for GAD, 4%
      (95% CI 2% to 6%) for social phobia, 8% (95% CI 5% to 11%) for specific phobia
      and 2% (95% CI 1% to 4%) for obsessive-compulsive disorder. Post-traumatic stress
      disorder (PTSD) prevalence was unclear due to higher levels of reluctance to
      respond to PTSD interview questions but sensitivity analyses suggest population
      prevalence maybe up to 4% (95% CI 2% to 6%). Weighted sensitivity of GAD-2 for
      GAD (cut-off >=3) was 69%, specificity 91%, positive predictive value 26%,
      negative predictive value 98% and likelihood ratio 7.35. For any anxiety disorder
      the weighted sensitivity was 26%, specificity 91%, positive predictive value 36%,
      negative predictive value 87% and likelihood ratio 2.92. CONCLUSIONS: Anxiety
      disorders are common but GAD-2 generates many false positives and may therefore
      be unhelpful in maternity services.

PMID- 30185584
TI  - Improving the sustainability of hospital-based interventions: a study protocol
      for a systematic review.
AB  - INTRODUCTION: Sustaining effective interventions in hospital environments is
      essential to improving health outcomes, and reducing research waste. Current
      evidence suggests many interventions are not sustained beyond their initial
      delivery. The reason for this failure remains unclear. Increasingly research is
      employing theoretical frameworks and models to identify critical factors that
      influence the implementation of interventions. However, little is known about the
      value of these frameworks on sustainability. The aim of this review is to examine
      the evidence regarding the use of theoretical frameworks to maximise effective
      intervention sustainability in hospital-based settings in order to better
      understand their role in supporting long-term intervention use. METHODS AND
      ANALYSIS: Systematic review. We will systematically search the following
      databases: Medline, AMED, CINAHL, Embase and Cochrane Library (CENTRAL, CDSR,
      DARE, HTA). We will also hand search relevant journals and will check the
      bibliographies of all included studies. Language and date limitations will be
      applied. We will include empirical studies that have used a theoretical framework
      (or model) and have explicitly reported the sustainability of an intervention (or
      programme). One reviewer will remove obviously irrelevant titles. The remaining
      abstracts and full-text articles will be screened by two independent reviewers to
      determine their eligibility for inclusion. Disagreements will be resolved by
      discussion, and may involve a third reviewer if required. Key study
      characteristics will be extracted (study design, population demographics,
      setting, evidence of sustained change, use of theoretical frameworks and any
      barriers or facilitators data reported) by one reviewer and cross-checked by
      another reviewer. Descriptive data will be tabulated within evidence tables, and
      key findings will be brought together within a narrative synthesis. ETHICS AND
      DISSEMINATION: Formal ethical approval is not required as no primary data will be
      collected. Dissemination of results will be through peer-reviewed journal
      publications, presentation at an international conference and social media.
      PROSPERO REGISTRATION NUMBER: CRD42017081992.

PMID- 30185583
TI  - High-flow nasal cannula oxygen therapy alone or with non-invasive ventilation
      during the weaning period after extubation in ICU: the prospective randomised
      controlled HIGH-WEAN protocol.
AB  - INTRODUCTION: Recent practice guidelines suggest applying non-invasive
      ventilation (NIV) to prevent postextubation respiratory failure in patients at
      high risk of extubation failure in intensive care unit (ICU). However, such
      prophylactic NIV has been only a conditional recommendation given the low
      certainty of evidence. Likewise, high-flow nasal cannula (HFNC) oxygen therapy
      has been shown to reduce reintubation rates as compared with standard oxygen and
      to be as efficient as NIV in patients at high risk. Whereas HFNC may be
      considered as an optimal therapy during the postextubation period, HFNC
      associated with NIV could be an additional means of preventing postextubation
      respiratory failure. We are hypothesising that treatment associating NIV with
      HFNC between NIV sessions may be more effective than HFNC alone and may reduce
      the reintubation rate in patients at high risk. METHODS AND ANALYSIS: This study
      is an investigator-initiated, multicentre randomised controlled trial comparing
      HFNC alone or with NIV sessions during the postextubation period in patients at
      high risk of extubation failure in the ICU. Six hundred patients will be
      randomised with a 1:1 ratio in two groups according to the strategy of
      oxygenation after extubation. The primary outcome is the reintubation rate within
      the 7 days following planned extubation. Secondary outcomes include the number of
      patients who meet the criteria for moderate/severe respiratory failure, ICU
      length of stay and mortality up to day 90. ETHICS AND DISSEMINATION: The study
      has been approved by the ethics committee and patients will be included after
      informed consent. The results will be submitted for publication in peer-reviewed
      journals. TRIAL REGISTRATION NUMBER: NCT03121482.

PMID- 30185586
TI  - GP at Hand opposes NHS England's plan to cut funding for digital providers.

PMID- 30185585
TI  - Values and preferences of men for undergoing prostate-specific antigen screening
      for prostate cancer: a systematic review.
AB  - OBJECTIVES: To investigate men's values and preferences regarding prostate
      specific antigen (PSA)-based screening for prostate cancer. DESIGN: Systematic
      review. DATA SOURCES: We searched MEDLINE, EMBASE, PsycINFO and grey literature
      up to 2 September 2017. ELIGIBILITY CRITERIA: Primary studies of men's values and
      preferences regarding the benefits and harms of PSA screening. DATA EXTRACTION
      AND SYNTHESIS: Two independent reviewers extracted data and assessed risk of bias
      with a modified version of a risk of bias tool for values and preferences
      studies, the International Patient Decision Aid Standards instrument V.3 and the
      Cochrane Collaboration risk of bias tool. RESULTS: We identified 4172 unique
      citations, of which 11 studies proved eligible. Five studies investigated PSA
      screening using a direct choice study design, whereas six used decisions aids
      displaying patient-important outcomes. The direct choice studies used different
      methodologies and varied considerably in the reporting of outcomes. Two studies
      suggested that men were willing to forego screening with a small benefit in
      prostate cancer mortality if it would decrease the likelihood of unnecessary
      treatment or biopsies. In contrast, one study reported that men were willing to
      accept a substantial overdiagnosis to reduce their risk of prostate cancer
      mortality. Among the six studies involving decision aids, willingness to undergo
      screening varied substantially from 37% when displaying a hypothetical reduction
      in mortality of 10 per 1000 men, to 44% when displaying a reduction in mortality
      of 7 per 1000. We found no studies that specifically investigated whether values
      and preferences differed among men with family history, of African descent or
      with lower socioeconomic levels. CONCLUSION: The variability of men's values and
      preferences reflect that the decision to screen is highly preference sensitive.
      Our review highlights the need for shared decision making in men considering
      prostate cancer screening. TRIAL REGISTRATION NUMBER: CRD42018095585.

PMID- 30185588
TI  - PJA1 Coordinates with the SMC5/6 Complex to Restrict DNA Viruses and Episomal
      Genes through Interferon-independent Manner.
AB  - Viral and episomal DNAs, as signs of infections and dangers, induce series of
      immune responses in the host, and cells must sense foreign DNAs to eliminate the
      invaders. Cell nucleus is not "immune privileged" and exerts intrinsic mechanisms
      to control nuclear replicating DNA viruses. Thus, it is important to understand
      the action of viral DNA sensing in the cell nucleus. Here, we reveal a mechanism
      of restriction of DNA viruses and episomal plasmids mediated by PJA1, a RING-H2
      E3 ubiquitin ligase. PJA1 restricts DNA viruses, hepatitis B virus (HBV) and
      herpes simplex virus-1 (HSV-1), but not RNA viruses, enterovirus 71 (EV71) and
      vesicular stomatitis virus (VSV). Similarly, PJA1 inhibits episomal plasmids, but
      not chromosome integrated reporters or endogenous genes. In addition, PJA1 has no
      effect on endogenous type I and II interferons (IFNs) and interferon stimulated
      genes (ISGs), suggesting that PJA1 silences DNA viruses independent of the IFN
      pathways. Interestingly, PJA1 interacts with the SMC5/6 complex (a complex
      essential for chromosome maintenance and HBV restriction) to facilitate the
      complex to bind viral and episomal DNAs in the cell nucleus. Moreover, treatment
      with inhibitors of DNA topoisomerases (Tops) and knock-down of Tops release PJA1
      mediated silence of viral and extrachromosomal DNAs. Taken together, this work
      demonstrates that PJA1 interacts with SMC5/6 and facilitates the complex to bind
      and eliminate viral and episomal DNAs through DNA Tops, and thus reveals a
      distinct mechanism underlying restriction of DNA viruses and foreign genes in the
      cell nucleus.IMPORTANCE DNA viruses, including hepatitis B virus and herpes
      simplex virus, induce series of immune responses in the host and lead to human
      public health concerns worldwide. In addition to cytokines in the cytoplasm,
      restriction of viral DNA in the nucleus is an important approach of host
      immunity. However, the mechanism of foreign DNA recognition and restriction in
      the cell nucleus is largely unknown. This work demonstrates that an important
      cellular factor (PJA1) suppresses DNA viruses and transfected plasmids
      independent of type I and II interferon (IFN) pathways. Instead, PJA1 interacts
      with the chromosome maintenance complex (SMC5/6) and facilitates the complex to
      recognize and bind viral and episomal DNAs and recruits DNA topoisomerases to
      restrict the foreign molecules. These results reveal a distinct mechanism
      underlying the silence of viral and episomal invaders in the cell nuclei, and
      suggest that PJA1 acts as a potential agent to preventing infectious and
      inflammatory diseases.

PMID- 30185587
TI  - The Coronavirus Transmissible Gastroenteritis Virus Evades the Type I Interferon
      Response through IRE1alpha-Mediated Manipulation of the MicroRNA miR-30a
      5p/SOCS1/3 Axis.
AB  - In host innate immunity, type I interferons (IFN-I) are major antiviral
      molecules, and coronaviruses have evolved diverse strategies to counter the IFN-I
      response during infection. Transmissible gastroenteritis virus (TGEV), a member
      of the Alphacoronavirus family, induces endoplasmic reticulum (ER) stress and
      significant IFN-I production after infection. However, how TGEV evades the IFN-I
      antiviral response despite the marked induction of endogenous IFN-I has remained
      unclear. Inositol-requiring enzyme 1 alpha (IRE1alpha), a highly conserved ER
      stress sensor with both kinase and RNase activities, is involved in the IFN
      response. In this study, IRE1alpha facilitated TGEV replication via
      downmodulating the host microRNA (miR) miR-30a-5p abundance. miR-30a-5p normally
      enhances IFN-I antiviral activity by directly targeting the negative regulators
      of Janus family kinase (JAK)-signal transducer and activator of transcription
      (STAT), the suppressor of cytokine signaling protein 1 (SOCS1), and SOCS3.
      Furthermore, TGEV infection increased SOCS1 and SOCS3 expression, which dampened
      the IFN-I antiviral response and facilitated TGEV replication. Importantly,
      compared with mock infection, TGEV infection in vivo resulted in decreased miR
      30a-5p levels and significantly elevated SOCS1 and SOCS3 expression in the piglet
      ileum. Taken together, our data reveal a new strategy used by TGEV to escape the
      IFN-I response by engaging the IRE1alpha-miR-30a-5p/SOCS1/3 axis, thus improving
      our understanding of how TGEV escapes host innate immune defenses.IMPORTANCE Type
      I interferons (IFN-I) play essential roles in restricting viral infections.
      Coronavirus infection induces ER stress and the interferon response, which
      reflects different adaptive cellular processes. An understanding of how
      coronavirus-elicited ER stress is actively involved in viral replication and
      manipulates the host IFN-I response has remained elusive. Here, TGEV inhibited
      host miR-30a-5p via the ER stress sensor IRE1alpha, which led to the increased
      expression of negative regulators of JAK-STAT signaling cascades, namely, SOCS1
      and SOCS3. Increased SOCS1 or SOCS3 expression impaired the IFN-I antiviral
      response, promoting TGEV replication. These findings enhance our understanding of
      the strategies used by coronaviruses to antagonize IFN-I innate immunity via
      IRE1alpha-mediated manipulation of the miR-30a-5p/SOCS axis, highlighting the
      crucial role of IRE1alpha in innate antiviral resistance and the potential of
      IRE1alpha as a novel target against coronavirus infection.

PMID- 30185589
TI  - Comparison of Adjuvanted-Whole Inactivated Virus and Live-Attenuated Virus
      Vaccines against Challenge with Contemporary, Antigenically Distinct H3N2
      Influenza A Viruses.
AB  - Influenza A viruses in swine (IAV-S) circulating in the United States of America
      are phylogenetically and antigenically distinct. A human H3 hemagglutinin (HA)
      was introduced into the IAV-S gene pool in the late 1990s, sustained continued
      circulation, and evolved into five monophyletic genetic clades, H3 clades IV-A to
      -E, after 2009. Across these phylogenetic clades, distinct antigenic clusters
      were identified, with three clusters (cyan, red, and green antigenic cluster)
      among the most frequently detected antigenic phenotypes (Abente EJ, Santos J,
      Lewis NS, Gauger PC, Stratton J, et al. J Virol 90:8266-8280, 2016,
      https://doi.org/10.1128/JVI.01002-16). Although it was demonstrated that
      antigenic diversity of H3N2 IAV-S was associated with changes at a few amino acid
      positions in the head of the HA, the implications of this diversity for vaccine
      efficacy were not tested. Using antigenically representative H3N2 viruses, we
      compared whole inactivated virus (WIV) and live-attenuated influenza virus (LAIV)
      vaccines for protection against challenge with antigenically distinct H3N2
      viruses in pigs. WIV provided partial protection against antigenically distinct
      viruses but did not prevent virus replication in the upper respiratory tract. In
      contrast, LAIV provided complete protection from disease and virus was not
      detected after challenge with antigenically distinct viruses.IMPORTANCE Due to
      the rapid evolution of the influenza A virus, vaccines require continuous strain
      updates. Additionally, the platform used to deliver the vaccine can have an
      impact on the breadth of protection. Currently, there are various vaccine
      platforms available to prevent influenza A virus infection in swine, and we
      experimentally tested two: adjuvanted-whole inactivated virus and live-attenuated
      virus. When challenged with an antigenically distinct virus, adjuvanted-whole
      inactivated virus provided partial protection, while live-attenuated virus
      provided effective protection. Additional strategies are required to broaden the
      protective properties of inactivated virus vaccines, given the dynamic antigenic
      landscape of cocirculating strains in North America, whereas live-attenuated
      vaccines may require less frequent strain updates, based on demonstrated cross
      protection. Enhancing vaccine efficacy to control influenza infections in swine
      will help reduce the impact they have on swine production and reduce the risk of
      swine-to-human transmission.

PMID- 30185590
TI  - Qualitative Differences in Capsidless L-Particles Released as a By-Product of
      Bovine Herpesvirus 1 and Herpes Simplex Virus 1 Infections.
AB  - Despite differences in the pathogenesis and host range of alphaherpesviruses,
      many stages of their morphogenesis are thought to be conserved. Here, an
      ultrastructural study of bovine herpesvirus 1 (BoHV-1) envelopment revealed
      profiles similar to those previously found for herpes simplex virus 1 (HSV-1),
      with BoHV-1 capsids associating with endocytic tubules. Consistent with the
      similarity of their genomes and envelopment strategies, the proteomic
      compositions of BoHV-1 and HSV-1 virions were also comparable. However, BoHV-1
      morphogenesis exhibited a diversity in envelopment events. First, heterogeneous
      primary envelopment profiles were readily detectable at the inner nuclear
      membrane of BoHV-1-infected cells. Second, the BoHV-1 progeny comprised not just
      full virions but also an abundance of capsidless, noninfectious light particles
      (L-particles) that were released from the infected cells in numbers similar to
      those of virions and in the absence of DNA replication. Proteomic analysis of
      BoHV-1 L-particles and the much less abundant HSV-1 L-particles revealed that
      they contained the same complement of envelope proteins as virions but showed
      variations in tegument content. In the case of HSV-1, the UL46 tegument protein
      was reproducibly found to be >6-fold enriched in HSV-1 L-particles. More
      strikingly, the tegument proteins UL36, UL37, UL21, and UL16 were depleted in
      BoHV-1 but not HSV-1 L-particles. We propose that these combined differences
      reflect the presence of truly segregated "inner" and "outer" teguments in BoHV-1,
      making it a critical system for studying the structure and process of
      tegumentation and envelopment.IMPORTANCE The alphaherpesvirus family includes
      viruses that infect humans and animals. Hence, not only do they have a
      significant impact on human health, but they also have a substantial economic
      impact on the farming industry. While the pathogenic manifestations of the
      individual viruses differ from host to host, their relative genetic compositions
      suggest similarity at the molecular level. This study provides a side-by-side
      comparison of the particle outputs from the major human pathogen HSV-1 and the
      veterinary pathogen BoHV-1. Ultrastructural and proteomic analyses have revealed
      that both viruses have broadly similar morphogenesis profiles and infectious
      virus compositions. However, the demonstration that BoHV-1 has the capacity to
      generate vast numbers of capsidless enveloped particles that differ from those
      produced by HSV-1 in composition implies a divergence in the cell biology of
      these viruses that impacts our general understanding of alphaherpesvirus
      morphogenesis.

PMID- 30185591
TI  - Herpes simplex virus-1 specifically targets human CD1d antigen presentation to
      enhance its pathogenicity.
AB  - Herpes simplex virus-1 (HSV-1) is one of the most prevalent herpes viruses in
      humans and represents a constant health threat to aged and immune-compromised
      populations. It is only partially known how HSV-1 interacts with the host immune
      system to efficiently establish their infection and latency. CD1d-restricted NKT
      cells are a critical arm of host innate immune system and play potent roles in
      anti-infection and anti-tumor immune responses. We previously discovered that
      upon infection, HSV-1 rapidly and efficiently down-regulates CD1d cell surface
      expression and suppresses the function of NKT cells. Furthermore, we identified
      that the viral serine/threonine protein kinase, US3, is a major viral factor down
      regulating CD1d during infection. Interestingly, neither HSV-1, nor its US3
      protein, efficiently inhibits mouse CD1d expression, suggesting that HSV-1 has co
      evolved with human immune system to specifically suppress human CD1d and NKT cell
      function for its pathogenesis. This is consistent with the fact that wild-type
      mice are mostly resistant to HSV-1 infection. On the other hand, in-vivo
      infection of CD1d-humanized mouse (human CD1d-knockin) showed that HSV-1 indeed
      can evade human CD1d function and establish infection in these mice. We also
      reported here that US3-deficient viruses can not efficiently infect hCD1d-knockin
      mice but infect mice lacking all NKT cells at a higher efficiency. Together these
      studies supported that HSV-1 evasion of human CD1d and NKT cell function as an
      important pathogenic factor for the virus. Our results also validated the potent
      roles of NKT cells in anti-herpesviral immune responses and pointed to the
      potentials of NKT cell ligands as adjuvants for future vaccine
      development.Importance Herpes simplex virus-1 (HSV-1) is among the most common
      human pathogens. Little is known regarding the exact mechanism how this virus
      evades human immune system, particularly the innate immune system. We previously
      reported that HSV-1 employs its protein kinase US3 to modulate the expression of
      the key antigen-presenting molecule, CD1d, to evade the antiviral function of NKT
      cells. Here we demonstrated that the virus has co-evolved with human CD1d and NKT
      cell system and the NKT cells indeed play potent roles in anti-HSV immune
      responses. These studies point to the great potential of exploring NKT cell
      ligands as adjuvants for HSV vaccines.

PMID- 30185592
TI  - The RNA Epitranscriptome of DNA Viruses.
AB  - RNA modifications have generated much interest in the virology field, as recent
      works have shown that many viruses harbor these marks and modify cellular marks.
      The most abundant mRNA modification in eukaryotic cells, N 6-methyladenosine
      (m6A), has been examined extensively at the genome-wide scale in both cellular
      and viral contexts. This Gem discusses the role of m6A in gene regulation and
      describes recent advancements in Kaposi's sarcoma-associated herpesvirus (KSHV)
      and simian virus 40 (SV40) research. We provide insights into future research
      related to m6A in DNA viruses.

PMID- 30185594
TI  - Development of a Pan-H1 Influenza Vaccine.
AB  - The efficacy of current seasonal influenza vaccines varies greatly, depending on
      the match to circulating viruses. Though most vaccines elicit strain-specific
      responses, some present cross-reactive epitopes that elicit antibodies against
      diverse viruses and remain unchanged and effective for several years (1). To
      determine whether combinations of specific H1 HA antigens stimulate immune
      responses that protect against diverse H1 influenza, we evaluated the antibody
      responses elicited by HA-ferritin nanoparticles derived from six evolutionarily
      divergent H1 sequences and two computationally optimized broadly reactive antigen
      (COBRA) HA antigens. Humoral responses were assessed against a panel of 16
      representative influenza virus strains from the past 80 years. HAs from the
      strains A/NewCaledonia/20/1999 (NC99), A/California/04/2009 (CA09),
      A/HongKong/117/1977 (HK77) or COBRA-X6 and P1 elicited neutralization against
      diverse strains, and a combination of these three wildtype HA- or two COBRA HA
      nanoparticles conferred significant additional breadth beyond that observed with
      any individual strain. Therefore, combinations of H1 HAs may potentially
      constitute a pan-H1 influenza vaccine.IMPORTANCE Seasonal influenza vaccines
      elicit strain-specific immune responses designed to protect against circulating
      viruses. Because these vaccines often show limited efficacy, the search for a
      broadly protective seasonal vaccine remains a priority. Among different influenza
      virus subtypes, H1N1 has long been circulating in humans and has caused pandemic
      outbreaks. In order to assess the potential of a multivalent HA combination
      vaccine to improve the breadth of protection against divergent H1N1 viruses, HA
      ferritin nanoparticles were made and evaluated in mice against a panel of
      historical and contemporary influenza virus strains. Trivalent combinations of H1
      nanoparticles improved the breadth of immunity against divergent H1 influenza
      viruses.

PMID- 30185593
TI  - Exchange Proteins Directly Activated by cAMP and Their Roles in Respiratory
      Syncytial Virus Infection.
AB  - Respiratory syncytial virus (RSV) is the leading cause of respiratory infection
      in young children and high-risk adults. However, a specific treatment for this
      viral infection is not currently available. In this study, we discovered that an
      exchange protein directly activated by cyclic AMP (EPAC) can serve as a potential
      therapeutic target for RSV. In both lower and upper epithelial cells, treatment
      with EPAC inhibitor (ESI-09), but not protein kinase A inhibitor (H89),
      significantly inhibits RSV replication and proinflammatory cytokine/chemokine
      induction. In addition, RSV-activated transcriptional factors belonging to the NF
      kappaB and IRF families are also suppressed by ESI-09. Through isoform-specific
      gene knockdown, we found that EPAC2, but not EPAC1, plays a dominant role in
      controlling RSV replication and virus-induced host responses. Experiments using
      both EPAC2 knockout and EPAC2-specific inhibitor support such roles of EPAC2.
      Therefore, EPAC2 is a promising therapeutic target to regulate RSV replication
      and associated inflammation.IMPORTANCE RSV is a serious public health problem, as
      it is associated with bronchiolitis, pneumonia, and asthma exacerbations.
      Currently no effective treatment or vaccine is available, and many molecular
      mechanisms regarding RSV-induced lung disease are still significantly unknown.
      This project aims to elucidate an important and novel function of a protein,
      called EPAC2, in RSV replication and innate inflammatory responses. Our results
      should provide an important insight into the development of new pharmacologic
      strategies against RSV infection, thereby reducing RSV-associated morbidity and
      mortality.

PMID- 30185595
TI  - Large-Scale Synonymous Substitutions in Cucumber Mosaic Virus RNA 3 Facilitate
      Amino Acid Mutations in the Coat Protein.
AB  - The effect of large-scale synonymous substitutions in a small icosahedral, single
      stranded RNA viral genome on virulence, viral titer, and protein evolution were
      analyzed. The coat protein (CP) gene of the Fny stain of cucumber mosaic virus
      (CMV) was modified. We created four CP mutants in which all the codons of nine
      amino acids in the 5' or 3' half of the CP gene were replaced by either the most
      frequently or the least frequently used synonymous codons in monocot plants. When
      the dicot host (Nicotiana benthamiana) was inoculated with these four CP mutants,
      viral RNA titers in uninoculated symptomatic leaves decreased, while all mutants
      eventually showed mosaic symptoms similar to those for the wild type. The codon
      adaptation index of these four CP mutants against dicot genes was similar to
      those of the wild-type CP gene, indicating that the reduction of viral RNA titer
      was due to deleterious changes of the secondary structure of RNAs 3 and 4. When
      two 5' mutants were serially passaged in N. benthamiana, viral RNA titers were
      rapidly restored but competitive fitness remained decreased. Although no nucleic
      acid changes were observed in the passaged wild-type CMV, one to three amino acid
      changes were observed in the synonymously mutated CP of each passaged virus,
      which were involved in recovery of viral RNA titer of 5' mutants. Thus, we
      demonstrated that deleterious effects of the large-scale synonymous substitutions
      in the RNA viral genome facilitated the rapid amino acid mutation(s) in the CP to
      restore the viral RNA titer.IMPORTANCE Recently, it has been known that
      synonymous substitutions in RNA virus genes affect viral pathogenicity and
      competitive fitness by alteration of global or local RNA secondary structure of
      the viral genome. We confirmed that large-scale synonymous substitutions in the
      CP gene of CMV resulted in decreased viral RNA titer. Importantly, when viral
      evolution was stimulated by serial-passage inoculation, viral RNA titer was
      rapidly restored, concurrent with a few amino acid changes in the CP. This novel
      finding indicates that the deleterious effects of large-scale nucleic acid
      mutations on viral RNA secondary structure are readily tolerated by structural
      changes in the CP, demonstrating a novel part of the adaptive evolution of an RNA
      viral genome. In addition, our experimental system for serial inoculation of
      large-scale synonymous mutants could uncover a role for new amino acid residues
      in the viral protein that have not been observed in the wild-type virus strains.

PMID- 30185596
TI  - Antibody-Mediated CD4 Depletion Induces Homeostatic CD4+ T Cell Proliferation
      without Detectable Virus Reactivation in Antiretroviral Therapy-Treated Simian
      Immunodeficiency Virus-Infected Macaques.
AB  - A major barrier to human immunodeficiency virus (HIV) eradication is the long
      term persistence of latently infected CD4+ T cells harboring integrated
      replication-competent virus. It has been proposed that the homeostatic
      proliferation of these cells drives long-term reservoir persistence in the
      absence of virus reactivation, thus avoiding cell death due to either virus
      mediated cytopathicity or immune effector mechanisms. Here, we conducted an
      experimental depletion of CD4+ T cells in eight antiretroviral therapy (ART)
      treated, simian immunodeficiency virus (SIV)-infected rhesus macaques (RMs) to
      determine whether the homeostatically driven CD4+ T-cell proliferation that
      follows CD4+ T-cell depletion results in reactivation of latent virus and/or
      expansion of the virus reservoir. After administration of the CD4R1 antibody, we
      observed a CD4+ T cell depletion of 65 to 89% in peripheral blood and 20 to 50%
      in lymph nodes, followed by a significant increase in CD4+ T cell proliferation
      during CD4+ T cell reconstitution. However, this CD4+ T cell proliferation was
      not associated with detectable increases in viremia, indicating that the
      homeostatic activation of CD4+ T cells is not sufficient to induce virus
      reactivation from latently infected cells. Interestingly, the homeostatic
      reconstitution of the CD4+ T cell pool was not associated with significant
      changes in the number of circulating cells harboring SIV DNA compared to results
      for the first postdepletion time point. This study indicates that, in ART-treated
      SIV-infected RMs, the homeostasis-driven CD4+ T-cell proliferation that follows
      experimental CD4+ T-cell depletion occurs in the absence of detectable
      reactivation of latent virus and does not increase the size of the virus
      reservoir as measured in circulating cells.IMPORTANCE Despite successful
      suppression of HIV replication with antiretroviral therapy, current treatments
      are unable to eradicate the latent virus reservoir, and treatment interruption
      almost invariably results in the reactivation of HIV even after decades of virus
      suppression. Homeostatic proliferation of latently infected cells is one
      mechanism that could maintain the latent reservoir. To understand the impact of
      homeostatic mechanisms on virus reactivation and reservoir size, we
      experimentally depleted CD4+ T cells in ART-treated SIV-infected rhesus macaques
      and monitored their homeostatic rebound. We find that depletion-induced
      proliferation of CD4+ T cells is insufficient to reactivate the viral reservoir
      in vivo Furthermore, the proportion of SIV DNA+ CD4+ T cells remains unchanged
      during reconstitution, suggesting that the reservoir is resistant to this
      mechanism of expansion at least in this experimental system. Understanding how T
      cell homeostasis impacts latent reservoir longevity could lead to the development
      of new treatment paradigms aimed at curing HIV infection.

PMID- 30185599
TI  - Persistent replication of HIV, HCV and HBV results in distinct gene expression
      profiles by human NK cells.
AB  - NK cells during chronic viral infection have been well studied in the past. We
      performed an unbiased next-generation RNA-sequencing approach to identify
      commonalities or differences of the effect of HIV, HCV and HBV viremia on NK cell
      transcriptomes. Using cell sorting, we obtained CD3-CD56+ NK cells from blood of
      6 HIV, 8 HCV, and 32 HBV infected patients without treatment. After library
      preparation and sequencing, we used an in-house analytic pipeline to compare
      expression levels with matched healthy controls. In NK cells from HIV, HCV and
      HBV patients, transcriptome analysis identified 272, 53, and 56 differentially
      expressed genes, respectively (fold change >1.5, q-value 0.2). Interferon
      stimulated genes were induced in NK cells from HIV/HCV patients, but not during
      HBV infection. HIV viremia downregulated ribosome assembly genes in NK cells. In
      HBV, viral load and ALT variation had little effect on genes related to NK
      effector function. In conclusion, we compare, for the first time, NK cell
      transcripts of viremic HIV, HCV and HBV patients. We clearly demonstrate
      distinctive NK cell gene signatures in 3 different populations, suggestive for a
      different degree of functional alterations of the NK cell compartment as compared
      to healthy individuals.Importance Three viruses exist that can result in
      persistently high viral loads in immune competent humans: HIV, hepatitis C and
      hepatitis B. In the last decades, using flow cytometry and in vitro assays on NK
      cells from patients with these diseases, several impairments have been
      established, particularly during and possibly contributing to HIV viremia.
      However, the background of NK cell impairments in viremic patients is not well
      understood. In this study we describe the NK cell transcriptome of patients with
      high viral loads of different etiologies. We clearly demonstrate distinctive NK
      cell gene signatures, with regard to ISG induction, expression of genes coding
      for activation markers or proteins involved in cytotoxic action, as well
      immunological genes. This study provides important details necessary to uncover
      the origin of functional and phenotypical differences between viremic patients
      and healthy subjects, and provides many leads that can be confirmed using future
      in vitro manipulation experiments.

PMID- 30185598
TI  - Potent Neutralizing Human Monoclonal Antibodies Preferentially Target Mature
      Dengue Virus Particles: Implication for Novel Strategy for Dengue Vaccine.
AB  - The four serotypes of dengue virus (DENV) cause the most important mosquito-borne
      viral disease in humans. The envelope (E) protein is the major target of
      neutralizing antibodies and contains 3 domains (domain I [DI], DII, and DIII).
      Recent studies reported that human monoclonal antibodies (MAbs) recognizing DIII,
      the D1/DII hinge, the E-dimer epitope, or a quaternary epitope involving
      DI/DII/DIII are more potently neutralizing than those recognizing the fusion loop
      (FL) of DII. Due to inefficient cleavage of the premembrane protein, DENV
      suspensions consist of a mixture of mature, immature, and partially immature
      particles. We investigated the neutralization and binding of 22 human MAbs to
      DENV serotype 1 (DENV1) virions with differential maturation status. Compared
      with FL MAbs, DIII, DI/DII hinge, and E-dimer epitope MAbs showed higher maximum
      binding and avidity to mature particles relative to immature particles; this
      feature may contribute to the strong neutralizing potency of such MAbs. FL
      specific MAbs required 57 to 87% occupancy on mature particles to achieve half
      maximal neutralization (NT50), whereas the potently neutralizing MAbs achieved
      NT50 states at 20 to 38% occupancy. Analysis of the MAb repertoire and polyclonal
      sera from patients with primary DENV1 infection supports the immunodominance of
      cross-reactive anti-E antibodies over type-specific antibodies. After depletion
      with viral particles from a heterologous DENV serotype, the type-specific
      neutralizing antibodies remained and showed binding features shared by potent
      neutralizing MAbs. Taken together, these findings suggest that the use of
      homogeneous mature DENV particles as an immunogen may induce more potent
      neutralizing antibodies against DENV than the use of immature or mixed
      particles.IMPORTANCE With an estimated 390 million infections per year, the four
      serotypes of dengue virus (DENV) cause the most important mosquito-borne viral
      disease in humans. The dengue vaccine Dengvaxia was licensed; however, its low
      efficacy among dengue-naive individuals and increased risk of causing severe
      dengue in children highlight the need for a better understanding of the role of
      human antibodies in immunity against DENV. DENV suspensions contain mature,
      immature, and partially immature particles. We investigated the binding of 22
      human monoclonal antibodies (MAbs) to the DENV envelope protein on particles with
      different maturation states. Potently neutralizing MAbs had higher relative
      maximum binding and avidity to mature particles than weakly neutralizing MAbs.
      This was supported by analysis of MAb repertoires and polyclonal sera from
      patients with primary DENV infection. Together, these findings suggest that
      mature particles may be the optimal form of presentation of the envelope protein
      to induce more potent neutralizing antibodies against DENV.

PMID- 30185597
TI  - A Proteomic Atlas of the African Swine Fever Virus Particle.
AB  - African swine fever virus (ASFV) is a large and complex DNA virus that causes a
      highly lethal swine disease for which there is no vaccine available. The ASFV
      particle, with an icosahedral multilayered structure, contains multiple
      polypeptides whose identity is largely unknown. Here, we analyzed by mass
      spectroscopy the protein composition of highly purified extracellular ASFV
      particles and performed immunoelectron microscopy to localize several of the
      detected proteins. The proteomic analysis identified 68 viral proteins, which
      account for 39% of the genome coding capacity. The ASFV proteome includes
      essentially all the previously described virion proteins and, interestingly, 44
      newly identified virus-packaged polypeptides, half of which have an unknown
      function. A great proportion of the virion proteins are committed to the virus
      architecture, including two newly identified structural proteins, p5 and p8,
      which are derived from the core polyproteins pp220 and pp62, respectively. In
      addition, the virion contains a full complement of enzymes and factors involved
      in viral transcription, various enzymes implicated in DNA repair and protein
      modification, and some proteins concerned with virus entry and host defense
      evasion. Finally, 21 host proteins, many of them localized at the cell surface
      and related to the cortical actin cytoskeleton, were reproducibly detected in the
      ASFV particle. Immunoelectron microscopy strongly supports the suggestion that
      these host membrane-associated proteins are recruited during virus budding at
      actin-dependent membrane protrusions. Altogether, the results of this study
      provide a comprehensive model of the ASFV architecture that integrates both
      compositional and structural information.IMPORTANCE African swine fever virus
      causes a highly contagious and lethal disease of swine that currently affects
      many countries of sub-Saharan Africa, the Caucasus, the Russian Federation, and
      Eastern Europe and has very recently spread to China. Despite extensive research,
      effective vaccines or antiviral strategies are still lacking, and many basic
      questions on the molecular mechanisms underlying the infective cycle remain. One
      such gap regards the composition and structure of the infectious virus particle.
      In the study described in this report, we identified the set of viral and host
      proteins that compose the virion and determined or inferred the localization of
      many of them. This information significantly increases our understanding of the
      biological and structural features of an infectious African swine fever virus
      particle and will help direct future research efforts.

PMID- 30185600
TI  - Long-term retreatment rates of cerebral aneurysms in a population-level cohort.
AB  - BACKGROUND: The likelihood of retreatment in patients undergoing procedures for
      cerebral aneurysms (CAs) has an important role in deciding the optimal treatment
      type. Existing determinations of retreatment rates, particularly for unruptured
      CAs, may not represent current clinical practice. OBJECTIVE: To use population
      level data to examine a large cohort of patients with treated CAs over a 10-year
      period to estimate retreatment rates for both ruptured and unruptured CAs and
      explore the effect of changing treatment practices. METHODS: We used
      administrative data from all non-federal hospitalizations in California (2005
      2011) and Florida (2005-2014) and identified patients with treated CAs. Surgical
      clipping (SC) and endovascular treatments (ETs) were defined by corresponding
      procedure codes and an accompanying code for ruptured or unruptured CA.
      Retreatment was defined as subsequent SC or ET. RESULTS: Among 19 482 patients
      with treated CAs, ET was performed in 12 007 (62%) patients and SC in 7475 (38%).
      9279 (48%) patients underwent treatment for unruptured CAs and 10203 (52%) for
      ruptured. Retreatment after 90 days occurred in 1624 (8.3%) patients (11.2% vs
      3.7%, ET vs SC). Retreatment rates for SC were greater in unruptured than in
      ruptured aneurysms (4.6% vs 3.1%), but the opposite was true for ET (10.6% vs
      11.8%). 85% of retreatments were within 2 years of the index treatment.
      Retreatment was associated with age (OR=0.99, 95% CI 0.98 to 0.99), female sex
      (OR=1.5, 95% CI 1.3 to 1.7), Hispanic versus white race (OR=0.86, 95% CI 0.75 to
      0.98), and ET versus SC (OR=3.25, 95% CI 2.85 to 3.71). The adjusted 2-year
      retreatment rate decreased from 2005 to 2012 for patients with unruptured CAs
      treated with ET (11% to 8%). CONCLUSIONS: Retreatment rates for CAs treated with
      ET were greater than those for SC. However, for patients with unruptured CAs
      treated with ET, we identify a continuous decline in retreatment rate over the
      past decade.

PMID- 30185602
TI  - Emerging approaches for detection of methylation sites in RNA.
AB  - RNA methylations play a significant regulatory role in diverse biological
      processes. Although the transcriptome-wide discovery of unknown RNA methylation
      sites is essential to elucidate their function, the development of a bigger
      variety of detection approaches is desirable for multiple reasons. Many
      established detection methods for RNA modifications heavily rely on the
      specificity of the respective antibodies. Thus, the development of antibody
      independent transcriptome-wide methods is beneficial. Even the antibody
      independent high-throughput sequencing-based methods are liable to produce false
      positive or false-negative results. The development of an independent method for
      each modification could help validate the detected modification sites. Apart from
      the transcriptome-wide methods for methylation detection de novo, methods for
      monitoring the presence of a single methylation at a determined site are also
      needed. In contrast to the transcriptome-wide detection methods, the techniques
      used for monitoring purposes need to be cheap, fast and easy to perform. This
      review considers modern approaches for site-specific detection of methylated
      nucleotides in RNA. We also discuss the potential of third-generation sequencing
      methods for direct detection of RNA methylations.

PMID- 30185606
TI  - Tail walking in a bottlenose dolphin community: the rise and fall of an arbitrary
      cultural 'fad'.
AB  - Social learning of adaptive behaviour is widespread in animal populations, but
      the spread of arbitrary behaviours is less common. In this paper, we describe the
      rise and fall of a behaviour called tail walking, where a dolphin forces the
      majority of its body vertically out of the water and maintains the position by
      vigourously pumping its tail, in a community of Indo-Pacific bottlenose dolphins
      (Tursiops aduncus). The behaviour was introduced into the wild following the
      rehabilitation of a wild female individual, Billie, who was temporarily co-housed
      with trained dolphins in a dolphinarium. This individual was sighted performing
      the behaviour seven years after her 1988 release, as was one other female dolphin
      named Wave. Initial production of the behaviour was rare, but following Billie's
      death two decades after her release, Wave began producing the behaviour at much
      higher rates, and several other dolphins in the community were subsequently
      sighted performing the behaviour. Social learning is the most likely mechanism
      for the introduction and spread of this unusual behaviour, which has no known
      adaptive function. These observations demonstrate the potential strength of the
      capacity for spontaneous imitation in bottlenose dolphins, and help explain the
      origin and spread of foraging specializations observed in multiple populations of
      this genus.

PMID- 30185605
TI  - Carbon stocks of mangroves and salt marshes of the Amazon region, Brazil.
AB  - In addition to the largest existing expanse of tropical forests, the Brazilian
      Amazon has among the largest area of mangroves in the world. While recognized as
      important global carbon sinks that, when disturbed, are significant sources of
      greenhouse gases, no studies have quantified the carbon stocks of these vast
      mangrove forests. In this paper, we quantified total ecosystem carbon stocks of
      mangroves and salt marshes east of the mouth of the Amazon River, Brazil. Mean
      ecosystem carbon stocks of the salt marshes were 257 Mg C ha-1 while those of
      mangroves ranged from 361 to 746 Mg C ha-1 Although aboveground mass was high
      relative to many other mangrove forests (145 Mg C ha-1), soil carbon stocks were
      relatively low (340 Mg C ha-1). Low soil carbon stocks may be related to coarse
      textured soils coupled with a high tidal range. Nevertheless, the carbon stocks
      of the Amazon mangroves were over twice those of upland evergreen forests and
      almost 10-fold those of tropical dry forests.

PMID- 30185601
TI  - Structural insights into the functional diversity of the CDK-cyclin family.
AB  - Since their characterization as conserved modules that regulate progression
      through the eukaryotic cell cycle, cyclin-dependent protein kinases (CDKs) in
      higher eukaryotic cells are now also emerging as significant regulators of
      transcription, metabolism and cell differentiation. The cyclins, though
      originally characterized as CDK partners, also have CDK-independent roles that
      include the regulation of DNA damage repair and transcriptional programmes that
      direct cell differentiation, apoptosis and metabolic flux. This review compares
      the structures of the members of the CDK and cyclin families determined by X-ray
      crystallography, and considers what mechanistic insights they provide to guide
      functional studies and distinguish CDK- and cyclin-specific activities. Aberrant
      CDK activity is a hallmark of a number of diseases, and structural studies can
      provide important insights to identify novel routes to therapy.

PMID- 30185604
TI  - Retrograde regulation of mossy fiber axon targeting and terminal maturation via
      postsynaptic Lnx1.
AB  - Neuronal connections are initiated by axon targeting to form synapses. However,
      how the maturation of axon terminals is modulated through interacting with
      postsynaptic elements remains elusive. In this study, we find that ligand of Numb
      protein X 1 (Lnx1), a postsynaptic PDZ protein expressed in hippocampal CA3
      pyramidal neurons, is essential for mossy fiber (MF) axon targeting during the
      postnatal period. Lnx1 deletion causes defective synaptic arrangement that leads
      to aberrant presynaptic terminals. We further identify EphB receptors as novel
      Lnx1-binding proteins to form a multiprotein complex that is stabilized on the
      CA3 neuron membrane through preventing proteasome activity. EphB1 and EphB2 are
      independently required to transduce distinct signals controlling MF pruning and
      targeting for precise DG-CA3 synapse formation. Furthermore, constitutively
      active EphB2 kinase rescues structure of the wired MF terminals in Lnx1 mutant
      mice. Our data thus define a retrograde trans-synaptic regulation required for
      integration of post- and presynaptic structure that participates in building
      hippocampal neural circuits during the adolescence period.

PMID- 30185607
TI  - Come on baby, let's do the twist: the kinematics of killing in loggerhead
      shrikes.
AB  - Shrikes use their beaks for procuring, dispatching and processing their arthropod
      and vertebrate prey. However, it is not clear how the raptor-like bill of this
      predatory songbird functions to kill vertebrate prey that may weigh more than the
      shrike itself. In this paper, using high-speed videography, we observed that upon
      seizing prey with their beaks, shrikes performed rapid (6-17 Hz; 49-71 rad s-1)
      axial head-rolling movements. These movements accelerated the bodies of their
      prey about their own necks at g-forces of approximately 6 g, and may be
      sufficient to cause pathological damage to the cervical vertebrae and spinal
      cord. Thus, when tackling relatively large vertebrates, shrikes appear to use
      inertia of their prey's own body against them.

PMID- 30185603
TI  - Synaptic dysfunction in neurodegenerative and neurodevelopmental diseases: an
      overview of induced pluripotent stem-cell-based disease models.
AB  - Synaptic dysfunction in CNS disorders is the outcome of perturbations in
      physiological synapse structure and function, and can be either the cause or the
      consequence in specific pathologies. Accumulating data in the field of
      neuropsychiatric disorders, including autism spectrum disorders, schizophrenia
      and bipolar disorder, point to a neurodevelopmental origin of these pathologies.
      Due to a relatively early onset of behavioural and cognitive symptoms, it is
      generally acknowledged that mental illness initiates at the synapse level. On the
      other hand, synaptic dysfunction has been considered as an endpoint incident in
      neurodegenerative diseases, such as Alzheimer's, Parkinson's and Huntington's,
      mainly due to the considerably later onset of clinical symptoms and progressive
      appearance of cognitive deficits. This dichotomy has recently been challenged,
      particularly since the discovery of cell reprogramming technologies and the
      generation of induced pluripotent stem cells from patient somatic cells. The
      creation of 'disease-in-a-dish' models for multiple CNS pathologies has revealed
      unexpected commonalities in the molecular and cellular mechanisms operating in
      both developmental and degenerative conditions, most of which meet at the synapse
      level. In this review we discuss synaptic dysfunction in prototype
      neurodevelopmental and neurodegenerative diseases, emphasizing overlapping
      features of synaptopathy that have been suggested by studies using induced
      pluripotent stem-cell-based systems. These valuable disease models have
      highlighted a potential neurodevelopmental component in classical
      neurodegenerative diseases that is worth pursuing and investigating further.
      Moving from demonstration of correlation to understanding mechanistic causality
      forms the basis for developing novel therapeutics.

PMID- 30185608
TI  - The interaction of exposure and warming tolerance determines fish species
      vulnerability to warming stream temperatures.
AB  - Species vulnerability to climate change involves an interaction between the
      magnitude of change (exposure) and a species's tolerance to change. We evaluated
      fish species vulnerability to predicted stream temperature increases by examining
      warming tolerances across the Wyoming fish assemblage. Warming tolerance combines
      stream temperature with a thermal tolerance metric to estimate how much warming
      beyond current conditions a species can withstand. Brown trout, rainbow trout and
      burbot had the lowest warming tolerances and the highest proportion of currently
      occupied sites that will become unsuitable under predicted temperature increases.
      These most vulnerable species were coldwater species, but had neither the lowest
      thermal tolerances nor would they experience the greatest temperature increases.
      Our results highlight the importance of considering the interaction of exposure
      and warming tolerance when predicting climate change vulnerability and
      demonstrate an approach that can be applied broadly.

PMID- 30185609
TI  - Quantifying the dark data in museum fossil collections as palaeontology undergoes
      a second digital revolution.
AB  - Large-scale analysis of the fossil record requires aggregation of
      palaeontological data from individual fossil localities. Prior to computers,
      these synoptic datasets were compiled by hand, a laborious undertaking that took
      years of effort and forced palaeontologists to make difficult choices about what
      types of data to tabulate. The advent of desktop computers ushered in
      palaeontology's first digital revolution-online literature-based databases, such
      as the Paleobiology Database (PBDB). However, the published literature represents
      only a small proportion of the palaeontological data housed in museum
      collections. Although this issue has long been appreciated, the magnitude, and
      thus potential significance, of these so-called 'dark data' has been difficult to
      determine. Here, in the early phases of a second digital revolution in
      palaeontology--the digitization of museum collections-we provide an estimate of
      the magnitude of palaeontology's dark data. Digitization of our nine
      institutions' holdings of Cenozoic marine invertebrate collections from
      California, Oregon and Washington in the USA reveals that they represent 23 times
      the number of unique localities than are currently available in the PBDB. These
      data, and the vast quantity of similarly untapped dark data in other museum
      collections, will, when digitally mobilized, enhance palaeontologists' ability to
      make inferences about the patterns and processes of past evolutionary and
      ecological changes.

PMID- 30185610
TI  - Tasting the unexpected: disconfirmation of expectations leads to lower perceived
      food value in an invertebrate.
AB  - To make sensible decisions, both humans and other animals must compare the
      available options against a reference point-either other options or previous
      experience. Options of higher quality than the reference are considered good
      value. However, many perceptible attributes of options are value-neutral, such as
      flower scent. Nonetheless, such value-neutral differences may be part of an
      expectation. Can a mismatch between the expectation and experience of value
      neutral attributes affect perceived value? Consumer psychology theory and results
      suggest it can. To test this in a non-human animal, we manipulated a value
      neutral aspect of a food source-its taste-while keeping its absolute value-its
      sweetness-the same. Individual ants (Lasius niger) were allowed to drink either
      lemon- or rosemary-flavoured 1 M sucrose. After three successive visits to the
      food, we switched the taste in the last, fourth, visit to induce a
      disconfirmation of expectations. In control trials, ants received the same taste
      on all four visits. Disconfirmed ants showed lower food acceptance and laid less
      pheromone on the way back to the nest, even though the molarity of the food was
      unchanged. As ants recruit nest-mates via pheromone depositions, fewer
      depositions indicate that the ants valued the food less. Thus, an expectation of
      value-neutral attributes can influence the perceived value of a resource. Such
      influences of value-neutral variables on value perception may affect how animals
      interact with and exploit their environment, and may contribute to phenomena such
      as flower constancy.

PMID- 30185611
TI  - Platelet communication with the vascular wall: role of platelet-derived
      microparticles and non-coding RNAs.
AB  - Platelets play an important role in vascular homeostasis through their
      interaction with circulating blood cells as well as the vascular wall. Platelet
      mediated communication with other cells can take the form of direct cell-cell
      interactions via membrane receptors or indirectly through the release of
      different soluble factors stored in their granules as well as through the release
      of microparticles. The latter carry different proteins and RNAs which are
      transferred to the target cells. The aim of this review is to discuss the role of
      platelet-derived factors, adhesion molecules as well as RNAs as mediators of the
      cross-talk between platelets and the vessel wall.

PMID- 30185612
TI  - Disordered haematopoiesis and cardiovascular disease: a focus on myelopoiesis.
AB  - Cardiovascular (CV) diseases (CVD) are primarily caused by atherosclerotic
      vascular disease. Atherogenesis is mainly driven by recruitment of leucocytes to
      the arterial wall, where macrophages contribute to both lipid retention as well
      as the inflammatory milieu within the vessel wall. Consequently, diseases which
      present with an enhanced abundance of circulating leucocytes, particularly
      monocytes, have also been documented to accelerate CVD. A host of metabolic and
      inflammatory diseases, such as obesity, diabetes, hypercholesteraemia, and
      rheumatoid arthritis (RA), have been shown to alter myelopoiesis to exacerbate
      atherosclerosis. Genetic evidence has emerged in humans with the discovery of
      clonal haematopoiesis of indeterminate potential (CHIP), resulting in a
      disordered haematopoietic system linked to accelerated atherogenesis. CHIP,
      caused by somatic mutations in haematopoietic stem and progenitor cells (HSPCs),
      consequently provide a proliferative advantage over native HSPCs and, in the case
      of Tet2 loss of function mutation, gives rise to inflammatory plaque macrophages
      (i.e. enhanced interleukin (IL)-1beta production). Together with the recent
      findings of the CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcomes Study)
      trial that revealed blocking IL-1beta using Canakinumab reduced CV events, these
      studies collectively have highlighted a pivotal role of IL-1beta signalling in a
      population of people with atherosclerotic CVD. This review will explore how
      haematopoiesis is altered by risk-factors and inflammatory disorders that promote
      CVD. Further, we will discuss some of the recent genetic evidence of disordered
      haematopoiesis in relation to CVD though the association with CHIP and suggest
      that future studies should explore what initiates HSPC mutations, as well as how
      current anti-inflammatory agents affect CHIP-driven atherosclerosis.

PMID- 30185614
TI  - T follicular helper cell development and functionality in immune ageing.
AB  - By 2050, there will be over 1.6 billion adults aged 65 years and older, making
      age-related diseases and conditions a growing public health concern. One of the
      leading causes of death in the ageing population is pathogenic infections (e.g.
      influenza, Streptococcus pneumoniae). This age-dependent susceptibility to
      infection has been linked to a reduced ability of the ageing immune system to
      mount protective responses against infectious pathogens, as well as to vaccines
      against these pathogens. The primary immune response that promotes protection is
      the production of antibodies by B cells - a response that is directly mediated by
      T follicular helper (TFH) cells within germinal centers (GCs) in secondary
      lymphoid tissues. In this review, we will summarize the current knowledge on the
      development and functionality of TFH cells, the use of circulating TFH (cTFH)
      cells as vaccine biomarkers, and the influence of age on these processes.
      Moreover, we will discuss the strategies for overcoming TFH cell dysfunction to
      improve protective antibody responses in the ageing human population.

PMID- 30185615
TI  - Coronary artery disease in post-menopausal women: are there appropriate means of
      assessment?
AB  - The recognition of sex differences in cardiovascular disease, particularly the
      manifestations of coronary artery disease (CAD) in post-menopausal women, has
      introduced new challenges in not only understanding disease mechanisms but also
      identifying appropriate clinical means of assessing the efficacy of management
      strategies. For example, the majority of treatment algorithms for CAD are derived
      from the study of males, focus on epicardial stenoses, and inadequately account
      for the small intramyocardial vessel disease in women. However, newer
      investigational modalities, including stress perfusion cardiac magnetic resonance
      imaging and positron emission tomography are providing enhanced diagnostic
      accuracy and prognostication for women with microvascular disease. Moreover,
      these investigations may soon be complemented by simpler screening tools such as
      retinal vasculature imaging, as well as novel biomarkers (e.g. heat shock protein
      27). Hence, it is vital that robust, sex-specific cardiovascular imaging
      modalities and biomarkers continue to be developed and are incorporated into
      practice guidelines that are used to manage women with CAD, as well as gauge the
      efficacy of any new treatment modalities. This review provides an overview of
      some of the sex differences in CAD and highlights emerging advances in the
      investigation of CAD in post-menopausal women.

PMID- 30185616
TI  - Molecular mechanism of the synergistic activity of ethambutol and isoniazid
      against Mycobacterium tuberculosis.
AB  - Isoniazid (INH) and ethambutol (EMB) are two major first-line drugs for managing
      tuberculosis (TB), caused by the microbe Mycobacterium tuberculosis Although co
      use of these two drugs is common in clinical practice, the mechanism for the
      potential synergistic interplay between them remains unclear. Here, we present
      first evidence that INH and EMB act synergistically through a transcriptional
      repressor of the inhA gene, the target gene of INH encoding an enoyl-acyl carrier
      protein reductase of the fatty acid synthase type II system required for
      bacterial cell wall integrity. We report that EMB binds a hypothetical
      transcription factor encoded by the Rv0273c gene, designated here as EtbR. Using
      DNA footprinting, we found that EtbR specifically recognizes a motif sequence in
      the upstream region of the inhA gene. Using isothermal titration calorimetry and
      surface plasmon resonance assays, we observed that EMB binds EtbR in a 1:1 ratio
      and thereby stimulates its DNA-binding activity. When a nonlethal dose of EMB was
      delivered in combination with INH, EMB increased the INH susceptibility of
      cultured M. tuberculosis cells. In summary, EMB induces EtbR-mediated repression
      of inhA and thereby enhances the mycobactericidal effect of INH. Our findings
      uncover a molecular mechanism for the synergistic activity of two important anti
      TB drugs.

PMID- 30185617
TI  - The nuclear transcription factor Rtg1p functions as a cytosolic, post
      transcriptional regulator in the methylotrophic yeast Pichia pastoris.
AB  - Rtg1p and Rtg3p are two basic helix-loop-helix, retrograde transcription factors
      in the budding yeast Saccharomyces cerevisiae Both factors heterodimerize to
      activate the transcription of nuclear genes in response to mitochondrial
      dysfunction and glutamate auxotrophy, but are not well characterized in other
      yeasts. Here, we demonstrate that the Rtg1p/Rtg3p-mediated retrograde signaling
      pathway is absent in the methylotrophic yeast Pichia pastoris We observed that P.
      pastoris Rtg1p (PpRtg1p) heterodimerizes with S. cerevisiae Rtg3p and functions
      as a nuclear, retrograde transcription factor in S. cerevisiae, but not in P.
      pastoris. We noted that P. pastoris Rtg3p lacks a functional leucine zipper and
      interacts with neither S. cerevisiae Rtg1p (ScRtg1p) nor PpRtg1p. In the absence
      of an interaction with Rtg3p, PpRtg1p has apparently acquired a novel function as
      a cytosolic regulator of multiple P. pastoris metabolic pathways, including
      biosynthesis of glutamate dehydrogenase 2 and phosphoenolpyruvate carboxykinase
      required for the utilization of glutamate as the sole carbon source. PpRtg1p also
      had an essential role in methanol metabolism and regulated alcohol oxidase
      synthesis and was required for the metabolism of ethanol, acetate, and oleic
      acid, but not of glucose and glycerol. Although PpRtg1p could functionally
      complement ScRtg1p, ScRtg1p could not complement PpRtg1p, indicating that ScRtg1p
      is not a functional PpRtg1p homolog. Thus, PpRtg1p functions as a nuclear,
      retrograde transcription factor in S. cerevisiae and as a cytosolic, post
      transcriptional regulator in P. pastoris We conclude that PpRtg1p is a key
      component of a signaling pathway that regulates multiple metabolic processes in
      P. pastoris.

PMID- 30185613
TI  - The classification, genetic diagnosis and modelling of monogenic autoinflammatory
      disorders.
AB  - Monogenic autoinflammatory disorders are an increasingly heterogeneous group of
      conditions characterised by innate immune dysregulation. Improved genetic
      sequencing in recent years has led not only to the discovery of a plethora of
      conditions considered to be 'autoinflammatory', but also the broadening of the
      clinical and immunological phenotypic spectra seen in these disorders. This
      review outlines the classification strategies that have been employed for
      monogenic autoinflammatory disorders to date, including the primary innate immune
      pathway or the dominant cytokine implicated in disease pathogenesis, and
      highlights some of the advantages of these models. Furthermore, the use of the
      term 'autoinflammatory' is discussed in relation to disorders that cross the
      innate and adaptive immune divide. The utilisation of next-generation sequencing
      (NGS) in this population is examined, as are potential in vivo and in vitro
      methods of modelling to determine pathogenicity of novel genetic findings.
      Finally, areas where our understanding can be improved are highlighted, such as
      phenotypic variability and genotype-phenotype correlations, with the aim of
      identifying areas of future research.

PMID- 30185618
TI  - Multi-tiered pairing selectivity between E2 ubiquitin-conjugating enzymes and E3
      ligases.
AB  - Ubiquitination is a prevalent post-translational modification involved in all
      aspects of cell physiology. It is mediated by an enzymatic cascade and the E2
      ubiquitin-conjugating enzymes (UBCs) lie at its heart. Even though E3 ubiquitin
      ligases determine the specificity of the reaction, E2s catalyze the attachment of
      ubiquitin and have emerged as key mediators of chain assembly. They are largely
      responsible for the type of linkage between ubiquitin moieties and thus, the fate
      endowed onto the modified substrate. However, in vivo E2-E3 pairing remains
      largely unexplored. We therefore interrogated the interaction selectivity between
      37 Arabidopsis E2s and PUB22, a U-box type E3 ubiquitin ligase that is involved
      in the dampening of immune signaling. We show that whereas the U-box domain,
      which mediates E2 docking, is able to interact with 18 of 37 tested E2s, the
      substrate interacting armadillo (ARM) repeats impose a second layer of
      specificity, allowing the interaction with 11 E2s. In vitro activity assayed by
      autoubiquitination only partially recapitulated the in vivo selectivity.
      Moreover, in vivo pairing was modulated during the immune response; pairing with
      group VI UBC30 was inhibited, whereas interaction with the K63 chain-building
      UBC35 was increased. Functional analysis of ubc35 ubc36 mutants shows that they
      partially mimic pub22 pub23 pub24 enhanced activation of immune responses.
      Together, our work provides a framework to interrogate in vivo E2-E3 pairing and
      reveals a multi-tiered and dynamic E2-E3 network.

PMID- 30185619
TI  - The dominant protein phosphatase PP1c isoform in smooth muscle cells, PP1cbeta,
      is essential for smooth muscle contraction.
AB  - Contractile force development of smooth muscle is controlled by balanced kinase
      and phosphatase activities toward the myosin regulatory light chain (RLC).
      Numerous biochemical and pharmacological studies have investigated the
      specificity and regulatory activity of smooth muscle myosin light-chain
      phosphatase (MLCP) bound to myosin filaments and comprised of the regulatory
      myosin phosphatase target subunit 1 (MYPT1) and catalytic protein phosphatase
      1cbeta (PP1cbeta) subunits. Recent physiological and biochemical evidence
      obtained with smooth muscle tissues from a conditional MYPT1 knockout suggests
      that a soluble, MYPT1-unbound form of PP1cbeta may additionally contribute to
      myosin RLC dephosphorylation and relaxation of smooth muscle. Using a combination
      of isoelectric focusing and isoform-specific immunoblotting, we found here that
      more than 90% of the total PP1c in mouse smooth muscles is the beta isoform.
      Moreover, conditional knockout of PP1calpha or PP1cgamma in adult smooth muscles
      did not result in an apparent phenotype in mice up to 6 months of age and did not
      affect smooth muscle contractions ex vivo In contrast, smooth muscle-specific
      conditional PP1cbeta knockout decreased contractile force development in bladder,
      ileal, and aortic tissues and reduced mouse survival. Bladder smooth muscle
      tissue from WT mice was selectively permeabilized to remove soluble PP1cbeta to
      measure contributions of total (alpha-toxin treatment) and myosin-bound (Triton X
      100 treatment) phosphatase activities toward phosphorylated RLC in myofilaments.
      Triton X-100 reduced PP1cbeta content by 60% and the rate of RLC
      dephosphorylation by 2-fold. These results are consistent with the selective
      dephosphorylation of RLC by both MYPT1-bound and -unbound PP1cbeta forms in
      smooth muscle.

PMID- 30185620
TI  - Dissecting MMP P10' and P11' subsite sequence preferences, utilizing a positional
      scanning, combinatorial triple-helical peptide library.
AB  - Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases
      that remodel the extracellular matrix environment and mitigate outside-in
      signaling. Loss of regulation of MMP activity plays a role in numerous
      pathological states. In particular, aberrant collagenolysis affects tumor
      invasion and metastasis, osteoarthritis, and cardiovascular and neurodegenerative
      diseases. To evaluate the collagen sequence preferences of MMPs, a positional
      scanning synthetic combinatorial library was synthesized herein and was used to
      investigate the P10' and P11' substrate subsites. The scaffold for the library
      was a triple-helical peptide mimic of the MMP cleavage site in types I-III
      collagen. A FRET-based enzyme activity assay was used to evaluate the sequence
      preferences of eight MMPs. Deconvolution of the library data revealed distinct
      motifs for several MMPs and discrimination among closely related MMPs. On the
      basis of the screening results, several individual peptides were designed and
      evaluated. A triple-helical substrate incorporating Asp-Lys in the P10'-P11'
      subsites offered selectivity between MMP-14 and MMP-15, whereas Asp-Lys or Trp
      Lys in these subsites discriminated between MMP-2 and MMP-9. Future screening of
      additional subsite positions will enable the design of selective triple-helical
      MMP probes that could be used for monitoring in vivo enzyme activity and enzyme
      facilitated drug delivery. Furthermore, selective substrates could serve as the
      basis for the design of specific triple-helical peptide inhibitors targeting only
      those MMPs that play a detrimental role in a disease of interest.

PMID- 30185621
TI  - Differential assembly of Rous sarcoma virus tetrameric and octameric intasomes is
      regulated by the C-terminal domain and tail region of integrase.
AB  - Retrovirus integrase (IN) catalyzes the concerted integration of linear viral DNA
      ends into chromosomes. The atomic structures of five different retrovirus IN-DNA
      complexes, termed intasomes, have revealed varying IN subunit compositions
      ranging from tetramers to octamers, dodecamers, and hexadecamers. Intasomes
      containing two IN-associated viral DNA ends capable of concerted integration are
      termed stable synaptic complexes (SSC), and those formed with a viral/target DNA
      substrate representing the product of strand-transfer reactions are strand
      transfer complexes (STC). Here, we investigated the mechanisms associated with
      the assembly of the Rous sarcoma virus SSC and STC. C-terminal truncations of WT
      IN (286 residues) indicated a role of the last 18 residues ("tail" region) in
      assembly of the tetrameric and octameric SSC, physically stabilized by HIV-1 IN
      strand-transfer inhibitors. Fine mapping through C-terminal truncations and site
      directed mutagenesis suggested that at least three residues (Asp-268-Thr-270)
      past the last beta-strand in the C-terminal domain (CTD) are necessary for
      assembly of the octameric SSC. In contrast, the assembly of the octameric STC was
      independent of the last 18 residues of IN. Single-site substitutions in the CTD
      affected the assembly of the SSC, but not necessarily of the STC, suggesting that
      STC assembly may depend less on specific interactions of the CTD with viral DNA.
      Additionally, we demonstrate that trans-communication between IN dimer-DNA
      complexes facilitates the association of native long-terminal repeat (LTR) ends
      with partially defective LTR ends to produce a hybrid octameric SSC. The
      differential assembly of the tetrameric and octameric SSC improves our
      understanding of intasomes.

PMID- 30185622
TI  - Molecular interactions connecting the function of the serine-arginine-rich
      protein SRSF1 to protein phosphatase 1.
AB  - Splicing generates many mRNA strands from a single precursor mRNA, expanding the
      proteome and enhancing intracellular diversity. Both initial assembly and
      activation of the spliceosome require an essential family of splicing factors
      called serine-arginine (SR) proteins. Protein phosphatase 1 (PP1) regulates the
      SR proteins by controlling phosphorylation of a C-terminal arginine-serine-rich
      (RS) domain. These modifications are vital for the subcellular localization and
      mRNA splicing function of the SR protein. Although PP1 has been shown to
      dephosphorylate the prototype SR protein splicing factor 1 (SRSF1), the molecular
      nature of this interaction is not understood. Here, using NMR spectroscopy, we
      identified two electrostatic residues in helix alpha2 and a hydrophobic residue
      in helix alpha1 in the RNA recognition motif 1 (RRM1) of SRSF1 that constitute a
      binding surface for PP1. Substitution of these residues dissociated SRSF1 from
      PP1 and enhanced phosphatase activity, reducing phosphorylation in the RS domain.
      These effects lead to shifts in alternative splicing patterns that parallel
      increases in SRSF1 diffusion from speckles to the nucleoplasm brought on by
      regiospecific decreases in RS domain phosphorylation. Overall, these findings
      establish a molecular and biological connection between PP1-targeted amino acids
      in an RRM with the phosphorylation state and mRNA-processing function of an SR
      protein.

PMID- 30185623
TI  - N-terminal Huntingtin (Htt) phosphorylation is a molecular switch regulating Htt
      aggregation, helical conformation, internalization, and nuclear targeting.
AB  - Huntington's disease is a fatal neurodegenerative disorder resulting from a CAG
      repeat expansion in the first exon of the gene encoding the Huntingtin protein
      (Htt). Phosphorylation of this protein region (Httex1) has been shown to play
      important roles in regulating the structure, toxicity, and cellular properties of
      N-terminal fragments and full-length Htt. However, increasing evidence suggests
      that phosphomimetic substitutions in Htt result in inconsistent findings and do
      not reproduce all aspects of true phosphorylation. Here, we investigated the
      effects of bona fide phosphorylation at Ser-13 or Ser-16 on the structure,
      aggregation, membrane binding, and subcellular properties of the Httex1-Q18A
      variant and compared these effects with those of phosphomimetic substitutions. We
      show that phosphorylation at either Ser-13 and/or Ser-16 or phosphomimetic
      substitutions at both these residues inhibit the aggregation of mutant Httex1,
      but that only phosphorylation strongly disrupts the amphipathic alpha-helix of
      the N terminus and prompts the internalization and nuclear targeting of preformed
      Httex1 aggregates. In synthetic peptides, phosphorylation at Ser-13, Ser-16, or
      both residues strongly disrupted the amphipathic alpha-helix of the N-terminal 17
      residues (Nt17) of Httex1 and Nt17 membrane binding. Experiments with peptides
      bearing different combinations of phosphorylation sites within Nt17 revealed a
      phosphorylation-dependent switch that regulates the Httex1 structure, involving
      cross-talk between phosphorylation at Thr-3 and Ser-13 or Ser-16. Our results
      provide crucial insights into the role of phosphorylation in regulating Httex1
      structure and function, and underscore the critical importance of identifying the
      enzymes responsible for regulating Htt phosphorylation, and their potential as
      therapeutic targets for managing Huntington's disease.

PMID- 30185625
TI  - With GBM, T Cells May Be Stuck in Bone Marrow.
AB  - A recent study uncovered a possible explanation for why patients with
      glioblastoma often have low levels of circulating T cells: The cells become
      sequestered in the bone marrow in high numbers, and are likely unable to leave
      because they lack the S1P1 receptor. The findings could lead to the development
      of more-effective immunotherapies.

PMID- 30185626
TI  - Study Explains Specificity of CRISPR/Cas12a.
AB  - A recent study reveals why the Cas12a genome-editing enzyme is more specific than
      the widely used Cas9. For Cas12a to cut, the guide RNA it carries must more
      closely match the sequence of the DNA target than with Cas9. The enzyme's
      specificity may make it a better choice for gene-editing applications.

PMID- 30185624
TI  - Oocyte-specific maternal Slbp2 is required for replication-dependent histone
      storage and early nuclear cleavage in zebrafish oogenesis and embryogenesis.
AB  - Stem-loop binding protein (SLBP) is required for replication-dependent histone
      mRNA metabolism in mammals. Zebrafish possesses two slbps, and slbp1 is necessary
      for retinal neurogenesis. However, the detailed expression and function of slbp2
      in zebrafish are still unknown. In this study, we first identified zebrafish
      slbp2 as an oocyte-specific maternal factor and then generated a maternal-zygotic
      slbp2 F3 homozygous mutant (MZslbp2Delta4-/-) using CRISPR/Cas9. The depletion of
      maternal Slbp2 disrupted early nuclear cleavage, which resulted in developmental
      arrest at the MBT stage. The developmental defects could be rescued in slbp2
      transgenic MZslbp2Delta4-/- embryos. However, homozygous mutant MZslbp1Delta1-/-
      developed normally, indicating slbp1 is dispensable for zebrafish early
      embryogenesis. Through comparative proteome and transcriptome profiling between
      WT and MZslbp2Delta4-/- embryos, we identified many differentially expressed
      proteins and genes. In comparison with those in WT embryos, four replication
      dependent histones, including H2a, H2b, H3, and H4, all reduced their expression,
      while histone variant h2afx significantly increased in MZslbp2Delta4-/- embryos
      at the 256-cell stage and high stage. Zebrafish Slbp2 can bind histone mRNA stem
      loop in vitro, and the defects of MZslbp2Delta4-/- embryos can be partially
      rescued by overexpression of H2b. The current data indicate that maternal Slbp2
      plays a pivotal role in the storage of replication-dependent histone mRNAs and
      proteins during zebrafish oogenesis.

PMID- 30185629
TI  - Childhood leukaemia: Novartis immunotherapy drug approved after deal with NHS.

PMID- 30185627
TI  - A Novel MCL1 Inhibitor Combined with Venetoclax Rescues Venetoclax-Resistant
      Acute Myelogenous Leukemia.
AB  - : Suppression of apoptosis by expression of antiapoptotic BCL2 family members is
      a hallmark of acute myeloblastic leukemia (AML). Induced myeloid leukemia cell
      differentiation protein (MCL1), an antiapoptotic BCL2 family member, is commonly
      upregulated in AML cells and is often a primary mode of resistance to treatment
      with the BCL2 inhibitor venetoclax. Here, we describe VU661013, a novel, potent,
      selective MCL1 inhibitor that destabilizes BIM/MCL1 association, leads to
      apoptosis in AML, and is active in venetoclax-resistant cells and patient-derived
      xenografts. In addition, VU661013 was safely combined with venetoclax for synergy
      in murine models of AML. Importantly, BH3 profiling of patient samples and drug
      sensitivity testing ex vivo accurately predicted cellular responses to selective
      inhibitors of MCL1 or BCL2 and showed benefit of the combination. Taken together,
      these data suggest a strategy of rationally using BCL2 and MCL1 inhibitors in
      sequence or in combination in AML clinical trials. SIGNIFICANCE: Targeting
      antiapoptotic proteins in AML is a key therapeutic strategy, and MCL1 is a
      critical antiapoptotic oncoprotein. Armed with novel MCL1 inhibitors and the
      potent BCL2 inhibitor venetoclax, it may be possible to selectively induce
      apoptosis by combining or thoughtfully sequencing these inhibitors based on a
      rational evaluation of AML.See related commentary by Leber et al., p. 1511.This
      article is highlighted in the In This Issue feature, p. 1494.

PMID- 30185630
TI  - Repetitive compound muscle action potential: a characteristic diagnostic clue.

PMID- 30185631
TI  - Hearing loss.
AB  - Hearing loss affects one in six people in the UK and is a significant disease
      burden. In addition to communication problems, there is also an association with
      depression and dementia. Clinical assessment with targeted history and
      examination can identify the characteristics and cause of hearing loss, and
      complementary audiological testing can confirm its type and severity.
      Retrocochlear screening is recommended for sudden, rapidly progressive or
      asymmetric sensorineural hearing loss. Medical or surgical therapies may be
      indicated in cases of conductive hearing loss, while hearing assistive devices
      and hearing aids are the mainstay of rehabilitation for sensorineural hearing
      loss.

PMID- 30185633
TI  - David Mitchell: US drug price warrior.

PMID- 30185628
TI  - Cholinergic Signaling via Muscarinic Receptors Directly and Indirectly Suppresses
      Pancreatic Tumorigenesis and Cancer Stemness.
AB  - In many solid tumors, parasympathetic input is provided by the vagus nerve, which
      has been shown to modulate tumor growth. However, whether cholinergic signaling
      directly regulates progression of pancreatic ductal adenocarcinoma (PDAC) has not
      been defined. Here, we found that subdiaphragmatic vagotomy in LSL-Kras
      +/G12D;Pdx1-Cre (KC) mice accelerated PDAC development, whereas treatment with
      the systemic muscarinic agonist bethanechol restored the normal KC phenotype,
      thereby suppressing the accelerated tumorigenesis caused by vagotomy. In LSL-Kras
      +/G12D;LSL-Trp53 +/R172H;Pdx1-Cre mice with established PDAC, bethanechol
      significantly extended survival. These effects were mediated in part through
      CHRM1, which inhibited downstream MAPK/EGFR and PI3K/AKT pathways in PDAC cells.
      Enhanced cholinergic signaling led to a suppression of the cancer stem cell (CSC)
      compartment, CD11b+ myeloid cells, TNFalpha levels, and metastatic growth in the
      liver. Therefore, these data suggest that cholinergic signaling directly and
      indirectly suppresses growth of PDAC cells, and therapies that stimulate
      muscarinic receptors may be useful in the treatment of PDAC.Significance:
      Subdiaphragmatic vagotomy or Chrm1 knockout accelerates pancreatic tumorigenesis,
      in part via expansion of the CSC compartment. Systemic administration of a
      muscarinic agonist suppresses tumorigenesis through MAPK and PI3K/AKT signaling,
      in early stages of tumor growth and in more advanced, metastatic disease.
      Therefore, CHRM1 may represent a potentially attractive therapeutic target.
      Cancer Discov; 8(11); 1458-73. (c)2018 AACR. This article is highlighted in the
      In This Issue feature, p. 1333.

PMID- 30185632
TI  - Gross negligence manslaughter and doctors: ethical concerns following the case of
      Dr Bawa-Garba.
AB  - Dr Bawa-Garba, a senior paediatric trainee who had been involved in the care of a
      child who died shortly after admission to hospital, was convicted of gross
      negligence manslaughter and subsequently erased from the medical register. We
      argue that criminalisation of doctors in this way is fraught with ethical
      tensions at levels of individual blameworthiness, systemic failures,
      professionalism, patient safety and at the interface of the regulator and doctor.
      The current response to alleged manslaughter during clinical care is not fit for
      purpose because of its narrow focus on criminalisation and punishment of
      individual doctors. The justice system fails to take into account systemic issues
      in a sufficiently proper and informed way particularly in respect of human
      factors involved in decision-making. It is easier to convict individual doctors
      for gross negligence manslaughter than it is to effect legal accountability upon
      organisations. If educational reflections are used to apportion blame, then this
      could impact detrimentally on honesty and the duty of candour, with negative
      implications for patient safety. Regulatory processes should not be deployed
      without consideration of context. There is an urgent need for a fresh and open
      evaluation of professional and societal expectations from the regulator that
      should include positive action as well as those that are proportionately
      punitive. Justice and patient safety would be served better by more sophisticated
      contextualisation through an approach that balances accountability in healthcare
      with failures that can occur within complex systems, and by working to a radical
      shift towards a just culture.

PMID- 30185634
TI  - Lupus antibodies induce behavioral changes mediated by microglia and blocked by
      ACE inhibitors.
AB  - Cognitive impairment occurs in 40-90% of patients with systemic lupus
      erythematosus (SLE), which is characterized by autoantibodies to nuclear
      antigens, especially DNA. We discovered that a subset of anti-DNA antibodies,
      termed DNRAbs, cross reacts with the N-methyl-d-aspartate receptor (NMDAR) and
      enhances NMDAR signaling. In patients, DNRAb presence associates with spatial
      memory impairment. In a mouse model, DNRAb-mediated brain pathology proceeds
      through an acute phase of excitotoxic neuron loss, followed by persistent
      alteration in neuronal integrity and spatial memory impairment. The latter
      pathology becomes evident only after DNRAbs are no longer detectable in the
      brain. Here we investigate the mechanism of long-term neuronal dysfunction
      mediated by transient exposure to antibody. We show that activated microglia and
      C1q are critical mediators of neuronal damage. We further show that centrally
      acting inhibitors of angiotensin-converting enzyme (ACE) can prevent microglial
      activation and preserve neuronal function and cognitive performance. Thus, ACE
      inhibition represents a strong candidate for clinical trials aimed at mitigating
      cognitive dysfunction.

PMID- 30185636
TI  - Camouflage strategies interfere differently with observer search images.
AB  - Numerous animals rely on camouflage for defence. Substantial past work has
      identified the presence of multiple strategies for concealment, and tested the
      mechanisms underpinning how they work. These include background matching, D-RUP
      coloration to destroy target edges, and distractive markings that may divert
      attention from key target features. Despite considerable progress, work has
      focused on how camouflage types prevent initial detection by naive observers.
      However, predators will often encounter multiple targets over time, providing the
      opportunity to learn or focus attention through search images. At present, we
      know almost nothing about how camouflage types facilitate or hinder predator
      performance over repeated encounters. Here, we use experiments with human
      subjects searching for targets on touch screens with different camouflage
      strategies, and control the experience that subjects have with target types. We
      show that different camouflage strategies affect how subjects improve in
      detecting targets with repeated encounters, and how performance in detection of
      one camouflage type depends on experience of other strategies. In particular,
      disruptive coloration is effective at preventing improvements in camouflage
      breaking during search image formation, and experience with one camouflage type
      (distraction) can decrease the ability of subjects to switch to and from search
      images for new camouflage types (disruption). Our study is, to our knowledge, the
      first to show how the success of camouflage strategies depends on how they
      prevent initial and successive detection, and on predator experience of other
      strategies. This has implications for the evolution of prey phenotypes, how we
      assess the efficacy of defences, and predator-prey dynamics.

PMID- 30185637
TI  - Regional climate and local-scale biotic acceptance explain native-exotic richness
      relationships in Australian annual plant communities.
AB  - Native and exotic species richness is expected to be negatively related at small
      spatial scales where individuals interact, and positive at larger spatial scales
      as a greater variety of habitats are sampled. However, a range of native-exotic
      richness relationships (NERRs) have been reported, including positive at small
      scales and negative at larger scales. We present a hierarchical metacommunity
      framework to explain how contrasting NERRs may emerge across scales and study
      systems, and then apply this framework to NERRs in an invaded winter annual plant
      system in southwest Western Australia. We analysed NERRs at increasing spatial
      scales from neighbourhoods (0.09 m2) to communities (225 m2) to metacommunities
      (greater than 10 ha) within a multilevel structural equation model. In contrast
      to many previous studies, native and exotic richness were positively related at
      the neighbourhood scale and were not significantly associated at larger scales.
      Heterogeneity in soil surface properties was weakly, but positively, associated
      with native and exotic richness at the community scale. Metacommunity exotic
      richness increased strongly with regional temperature and moisture availability,
      but relationships for native richness were negative and much weaker. Thus, we
      show that neutral NERRs can emerge at larger scales owing to differential
      climatic filtering of native and exotic species pools.

PMID- 30185635
TI  - Rapid CLIP dissociation from MHC II promotes an unusual antigen presentation
      pathway in autoimmunity.
AB  - A number of autoimmunity-associated MHC class II proteins interact only weakly
      with the invariant chain-derived class II-associated invariant chain peptide
      (CLIP). CLIP dissociates rapidly from I-Ag7 even in the absence of DM, and this
      property is related to the type 1 diabetes-associated beta57 polymorphism. We
      generated knock-in non-obese diabetic (NOD) mice with a single amino acid change
      in the CLIP segment of the invariant chain in order to moderately slow CLIP
      dissociation from I-Ag7 These knock-in mice had a significantly reduced incidence
      of spontaneous type 1 diabetes and diminished islet infiltration by CD4 T cells,
      in particular T cells specific for fusion peptides generated by covalent linkage
      of proteolytic fragments within beta cell secretory granules. Rapid CLIP
      dissociation enhanced the presentation of such extracellular peptides, thus
      bypassing the conventional MHC class II antigen-processing pathway. Autoimmunity
      associated MHC class II polymorphisms therefore not only modify binding of self
      peptides, but also alter the biochemistry of peptide acquisition.

PMID- 30185638
TI  - The emergence and selection of reputation systems that drive cooperative
      behaviour.
AB  - Reputational concerns are believed to play a crucial role in explaining
      cooperative behaviour among non-kin humans. Individuals cooperate to avoid a
      negative social image, if being branded as defector reduces pay-offs from future
      interactions. Similarly, individuals sanction defectors to gain a reputation as
      punisher, prompting future co-players to cooperate. But reputation can only
      effectively support cooperation if a sufficient number of individuals condition
      their strategies on their co-players' reputation, and if a sufficient number of
      group members are willing to record and transmit the relevant information about
      past actions. Using computer simulations, this paper argues that starting from a
      pool of non-cooperative individuals, a reputation system based on punishment is
      likely to emerge and to be the driver of the initial evolution of cooperative
      behaviour. However, once cooperation is established in a group, it will be
      sustained mainly through a reputation mechanism based on cooperative actions.

PMID- 30185639
TI  - Temperature drives diversification in a model adaptive radiation.
AB  - The warmer regions harbour more species, attributable to accelerated speciation
      and increased ecological opportunities for coexistence. While correlations
      between temperature and energy availability and habitat area have been suggested
      as major drivers of these biodiversity patterns, temperature can theoretically
      also have direct effects on the evolution of diversity. Here, we experimentally
      studied the evolution of diversity in a model adaptive radiation of the bacterium
      Pseudomonas fluorescens across a temperature gradient. Diversification increased
      at higher temperatures, driven by both faster generation of genetic variation and
      stronger diversifying selection. Specifically, low temperatures could limit the
      generation of diversity, suggested by the observation that supply of genetic
      variation through immigration increased diversity at low, but not high
      temperatures. The two major determinants of mutation supply, population size and
      mutation rate, both showed a positive temperature dependence. Stronger
      diversifying selection in warmer environments was suggested by promoted
      coexistence, and further explicitly inferred by the ability of evolved phenotypes
      to invade the ancestral type from rare. We discuss possible physiological and
      environmental mechanisms underlying the findings, most of which are likely to be
      general.

PMID- 30185640
TI  - The benefit of being still: energy savings during winter dormancy in fish come
      from inactivity and the cold, not from metabolic rate depression.
AB  - Winter dormancy is used by many animals to survive the cold and food-poor high
      latitude winter. Metabolic rate depression, an active downregulation of resting
      cellular energy turnover and thus standard (resting) metabolic rate (SMR), is a
      unifying strategy underlying the persistence of organisms in such energy-limited
      environments, including hibernating endotherms. However, controversy exists about
      its involvement in winter-dormant aquatic ectotherms. To address this debate, we
      conducted simultaneous, multi-day measurements of whole-animal oxygen consumption
      rate (a proxy of metabolic rate) and spontaneous movement in a model winter
      dormant marine fish, the cunner (Tautogolabrus adspersus). Winter dormancy in
      cunner involved a dampened diel rhythm of metabolic rate, such that a low and
      stable metabolic rate persisted throughout the 24 h day. Based on the thermal
      sensitivity (Q10) of SMR as well as correlations of metabolic rate and movement,
      the reductions in metabolic rate were not attributable to metabolic rate
      depression, but rather to reduced activity under the cold and darkness typical of
      the winter refuge among substrate. Previous reports of metabolic rate depression
      in cunner, and possibly other fish species, during winter dormancy were probably
      confounded by variation in activity. Unlike hibernating endotherms, and excepting
      the few fish species that overwinter in anoxic waters, winter dormancy in fishes,
      as exemplified by cunner, need not involve metabolic rate depression. Rather,
      energy savings come from inactivity combined with passive physico-chemical
      effects of the cold on SMR, demonstrating that thermal effects on activity can
      greatly influence temperature-metabolism relationships, and illustrating the
      benefit of simply being still in energy-limited environments.

PMID- 30185641
TI  - Seagrass digestion by a notorious 'carnivore'.
AB  - What an animal consumes and what an animal digests and assimilates for energetic
      demands are not always synonymous. Sharks, uniformly accepted as carnivores, have
      guts that are presumed to be well suited for a high-protein diet. However, the
      bonnethead shark (Sphyrna tiburo), which is abundant in critical seagrass
      habitats, has been previously shown to consume copious amounts of seagrass (up to
      62.1% of gut content mass), although it is unknown if they can digest and
      assimilate seagrass nutrients. To determine if bonnetheads digest seagrass
      nutrients, captive sharks were fed a 13C-labelled seagrass diet. Digestibility
      analyses, digestive enzyme assays and stable isotope analyses were used to
      determine the bonnethead shark's capacity for digesting and assimilating seagrass
      material. Compound-specific stable isotope analysis showed that sharks
      assimilated seagrass carbon (13.6 +/- 6.770/00 delta13C mean +/- s.d. for all
      sharks and all amino acid types analysed) with 50 +/- 2% digestibility of
      seagrass organic matter. Additionally, cellulose-component-degrading enzyme
      activities were detected in shark hindguts. We show that a coastal shark is
      digesting seagrass with at least moderate efficiency, which has ecological
      implications due to the stabilizing role of omnivory and nutrient transport
      within fragile seagrass ecosystems.

PMID- 30185642
TI  - Wear, tear and systematic repair: testing models of growth dynamics in conodonts
      with high-resolution imaging.
AB  - Conodont elements are the earliest mineralized vertebrate dental tools and the
      only ones capable of extensive repair. Two models of conodont growth, as well as
      the presence of a larval stage, have been hypothesized. We analysed normally and
      pathologically developed elements to test these hypotheses and identified three
      ontogenetic stages characterized by different anisometric growth and morphology.
      The distinction of these stages is independently corroborated by differences in
      tissue strontium (Sr) content. The onset of the last stage is marked by the
      appearance of wear resulting from mechanical food digestion. At least five
      episodes of damage and repair could be identified in the normally developed
      specimen. In the pathological element, function was compromised by the
      development of abnormal denticles. This development can be reconstructed as
      addition of new growth centres out of the main growth axis during an episode of
      renewed growth. Our findings support the model of periodic retraction of elements
      and addition of new growth centres. Changes in Sr content coincident with
      distinct morphology and lack of wear in the early life stage indicate that
      conodonts might have assumed their mature feeding habit of predators or
      scavengers after an initial larval stage characterized by a different feeding
      mode.

PMID- 30185643
TI  - Correction to 'Adaptive evolution of distinct prey-specific toxin genes in rear
      fanged snake venom'.

PMID- 30185644
TI  - Correction to 'The onset of ecological diversification 50 years after
      colonization of a crater lake by haplochromine cichlid fishes'.

PMID- 30185645
TI  - Indirect ecological effects interact with community genetic effects in a host
      parasite system and dramatically reduce parasite burden.
AB  - Community genetic (CG) effects and ecological factors create a complex set of
      interactions that are key drivers of evolutionary dynamics in ecological systems.
      To date, most studies investigating trait variation have focused on either
      effects of intraspecific genetic variation or on genotype by environment (GxE)
      interactions in isolation. Poorly investigated but very important are the
      interactions between CGs and indirect ecological effects (IEEs) that are caused
      by plant-soil interactions. Here, we tested how CGs in a cabbage host and its
      aphid parasite depended on the ecological conditions under which the host was
      grown. We established microcosms of different cabbage cultivars and aphid
      genotypes on soils inoculated with samples of other soils previously trained with
      onion. We hypothesized that such IEEs will have significantly different outcomes
      for ecosystems than predicted from simpler CG or GxE studies. Our analysis
      demonstrated a large IEE that differed by context and aphid genotype causing
      reduced parasite population sizes by up to 90%. The IEE is induced by insect
      repellent properties and the microbiome of the onion. Our results highlight the
      importance of interacting IEEs and CGs for ecosystems dynamics showing that IEEs
      offer sustainable solutions by dramatically reducing parasite burden on cash
      crops.

PMID- 30185647
TI  - Integrating the aesthetic value of landscapes and biological diversity.
AB  - As a cultural ecosystem service, the aesthetic value of landscapes contributes to
      human well-being, but studies linking biodiversity and ecosystem services
      generally do not account for this particular service. Therefore, congruence
      between the aesthetic perception of landscapes, ecological value and biodiversity
      remains poorly understood. Here, we describe the conceptual background, current
      methodologies and future challenges of assessing landscape aesthetics and its
      relationship with biodiversity. We highlight the methodological gaps between the
      assessment of landscape aesthetics, ecological diversity and functioning. We
      discuss the challenges associated with connecting landscape aesthetics with
      ecological value, and the scaling issues in the assessment of human aesthetics
      perception. To better integrate aesthetic value and ecological components of
      biodiversity, we propose to combine the study of aesthetics and the understanding
      of ecological function at both the species and landscape levels. Given the urgent
      need to engage society in conservation efforts, this approach, based on the
      combination of the aesthetic experience and the recognition of ecological
      functioning by the general public, will help change our culture of nature and
      promote ecologically oriented conservation policies.

PMID- 30185646
TI  - Host defences against avian brood parasitism: an endocrine perspective.
AB  - Host defences against avian brood parasites are the outcome of well-documented
      coevolutionary arms races, yet important questions about variation in hosts'
      antiparasitic response traits remain poorly understood. Why are certain defences
      employed by some species or individuals and not by others? Here, we propose that
      understanding variability in and the evolution of host defences can be
      facilitated by the study of the underlying physiological mechanisms.
      Specifically, because antiparasitic strategies involve behaviours that have been
      shown to be hormonally regulated in other contexts, we hypothesize that host
      responses to brood parasites are likely to be mediated by related endocrine
      mechanisms. We outline the hallmarks of the endocrine bases of parasite defence
      related avian behaviours, review the current understanding of antiparasitic host
      tactics and propose testable hypotheses about the hormonal mechanisms that may
      mediate host defences. We consider these mechanisms in a life-history framework
      and discuss how endocrine factors may shape variation in host defences. By
      providing a hypothesis-driven mechanistic framework for defences against
      parasitism, this perspective should stimulate the study of their endocrine bases
      to enhance our understanding of the intricate arms races in avian host-parasite
      systems.

PMID- 30185648
TI  - Jealous females? Female competition and reproductive suppression in a wild
      promiscuous primate.
AB  - Female-female competition over paternal care has rarely been investigated in
      promiscuous mammals, where discreet forms of male care have recently been
      reported despite low paternity certainty. We investigated female competition over
      paternal care in a wild promiscuous primate, the chacma baboon (Papio ursinus),
      where pregnant and lactating females establish strong social bonds (friendships)
      with males that provide care to their offspring. We tested whether pregnant and
      lactating females interfere with the sexual activity of their male friend to
      prevent new conceptions that might lead to the subsequent dilution of his
      paternal care. We found that pregnant and lactating females were more aggressive
      towards oestrous females when they had recently conceived themselves, and when
      the oestrous female was mate-guarded by, and showed greater sexual activity with,
      their male friend. This aggression also reduced the likelihood of conception of
      the targeted female. These findings indicate that females can aggressively
      prevent further conceptions with their offspring's carer through reproductive
      suppression. Competition over access to paternal care may play an important and
      underestimated role in shaping female social relationships and reproductive
      strategies in promiscuous mammalian societies.

PMID- 30185649
TI  - Social interactions shape individual and collective personality in social
      spiders.
AB  - The behavioural composition of a group and the dynamics of social interactions
      can both influence how social animals work collectively. For example, individuals
      exhibiting certain behavioural tendencies may have a disproportionately large
      impact on the group, and so are referred to as keystone individuals, while
      interactions between individuals can facilitate information transmission about
      resources. Despite the potential impact of both behavioural composition and
      interactions on collective behaviour, the relationship between consistent
      behaviours (also known as personalities) and social interactions remains poorly
      understood. Here, we use stochastic actor-oriented models to uncover the
      interdependencies between boldness and social interactions in the social spider
      Stegodyphus dumicola We find that boldness has no effect on the likelihood of
      forming social interactions, but interactions do affect boldness, and lead to an
      increase in the boldness of the shyer individual. Furthermore, spiders tend to
      interact with the same individuals as their neighbours. In general, boldness
      decreases over time, but once an individual's boldness begins to increase, this
      increase accelerates, suggesting a positive feedback mechanism. These dynamics of
      interactions and boldness result in skewed boldness distributions of a few bold
      individuals and many shy individuals, as observed in nature. This group
      behavioural composition facilitates efficient collective behaviours, such as
      rapid collective prey attack. Thus, by examining the relationship between
      behaviour and interactions, we reveal the mechanisms that underlie the emergence
      of adaptive group composition and collective behaviour.

PMID- 30185650
TI  - Hypercapnia increases airway smooth muscle contractility via caspase-7-mediated
      miR-133a-RhoA signaling.
AB  - The elevation of carbon dioxide (CO2) in tissues and the bloodstream
      (hypercapnia) occurs in patients with severe lung diseases, including chronic
      obstructive pulmonary disease (COPD). Whereas hypercapnia has been recognized as
      a marker of COPD severity, a role for hypercapnia in disease pathogenesis remains
      unclear. We provide evidence that CO2 acts as a signaling molecule in mouse and
      human airway smooth muscle cells. High CO2 activated calcium-calpain signaling
      and consequent smooth muscle cell contraction in mouse airway smooth muscle
      cells. The signaling was mediated by caspase-7-induced down-regulation of the
      microRNA-133a (miR-133a) and consequent up-regulation of Ras homolog family
      member A and myosin light-chain phosphorylation. Exposure of wild-type, but not
      caspase-7-null, mice to hypercapnia increased airway contraction and resistance.
      Deletion of the Caspase-7 gene prevented hypercapnia-induced airway
      contractility, which was restored by lentiviral transfection of a miR-133a
      antagonist. In a cohort of patients with severe COPD, hypercapnic patients had
      higher airway resistance, which improved after correction of hypercapnia. Our
      data suggest a specific molecular mechanism by which the development of
      hypercapnia may drive COPD pathogenesis and progression.

PMID- 30185651
TI  - Human thymopoiesis is influenced by a common genetic variant within the TCRA-TCRD
      locus.
AB  - The thymus is the primary lymphoid organ where naive T cells are generated;
      however, with the exception of age, the parameters that govern its function in
      healthy humans remain unknown. We characterized the variability of thymic
      function among 1000 age- and sex-stratified healthy adults of the Milieu
      Interieur cohort, using quantification of T cell receptor excision circles
      (TRECs) in peripheral blood T cells as a surrogate marker of thymopoiesis. Age
      and sex were the only nonheritable factors identified that affect thymic
      function. TREC amounts decreased with age and were higher in women compared to
      men. In addition, a genome-wide association study revealed a common variant
      (rs2204985) within the T cell receptor TCRA-TCRD locus, between the DD2 and DD3
      gene segments, which associated with TREC amounts. Strikingly, transplantation of
      human hematopoietic stem cells with the rs2204985 GG genotype into
      immunodeficient mice led to thymopoiesis with higher TRECs, increased thymocyte
      counts, and a higher TCR repertoire diversity. Our population immunology approach
      revealed a genetic locus that influences thymopoiesis in healthy adults, with
      potentially broad implications in precision medicine.

PMID- 30185652
TI  - A machine learning approach for somatic mutation discovery.
AB  - Variability in the accuracy of somatic mutation detection may affect the
      discovery of alterations and the therapeutic management of cancer patients. To
      address this issue, we developed a somatic mutation discovery approach based on
      machine learning that outperformed existing methods in identifying experimentally
      validated tumor alterations (sensitivity of 97% versus 90 to 99%; positive
      predictive value of 98% versus 34 to 92%). Analysis of paired tumor-normal exome
      data from 1368 TCGA (The Cancer Genome Atlas) samples using this method revealed
      concordance for 74% of mutation calls but also identified likely false-positive
      and false-negative changes in TCGA data, including in clinically actionable
      genes. Determination of high-quality somatic mutation calls improved tumor
      mutation load-based predictions of clinical outcome for melanoma and lung cancer
      patients previously treated with immune checkpoint inhibitors. Integration of
      high-quality machine learning mutation detection in clinical next-generation
      sequencing (NGS) analyses increased the accuracy of test results compared to
      other clinical sequencing analyses. These analyses provide an approach for
      improved identification of tumor-specific mutations and have important
      implications for research and clinical management of cancer patients.

PMID- 30185653
TI  - Eosinophils increase airway sensory nerve density in mice and in human asthma.
AB  - In asthma, airway nerve dysfunction leads to excessive bronchoconstriction and
      cough. It is well established that eosinophils alter nerve function and that
      airway eosinophilia is present in 50 to 60% of asthmatics. However, the effects
      of eosinophils on airway nerve structure have not been established. We tested
      whether eosinophils alter airway nerve structure and measured the physiological
      consequences of those changes. Our results in humans with and without
      eosinophilic asthma showed that airway innervation and substance P expression
      were increased in moderate persistent asthmatics compared to mild intermittent
      asthmatics and healthy subjects. Increased innervation was associated with a lack
      of bronchodilator responsiveness and increased irritant sensitivity. In a mouse
      model of eosinophilic airway inflammation, the increase in nerve density and
      airway hyperresponsiveness were mediated by eosinophils. Our results implicate
      airway nerve remodeling as a key mechanism for increased irritant sensitivity and
      exaggerated airway responsiveness in eosinophilic asthma.

PMID- 30185655
TI  - Impaired monocyte cholesterol clearance initiates age-related retinal
      degeneration and vision loss.
AB  - Advanced age-related macular degeneration (AMD), the leading cause of blindness
      among people over 50 years of age, is characterized by atrophic neurodegeneration
      or pathologic angiogenesis. Early AMD is characterized by extracellular
      cholesterol-rich deposits underneath the retinal pigment epithelium (RPE) called
      drusen or in the subretinal space called subretinal drusenoid deposits (SDD) that
      drive disease progression. However, mechanisms of drusen and SDD biogenesis
      remain poorly understood. Although human AMD is characterized by abnormalities in
      cholesterol homeostasis and shares phenotypic features with atherosclerosis, it
      is unclear whether systemic immunity or local tissue metabolism regulates this
      homeostasis. Here, we demonstrate that targeted deletion of macrophage
      cholesterol ABC transporters A1 (ABCA1) and -G1 (ABCG1) leads to age-associated
      extracellular cholesterol-rich deposits underneath the neurosensory retina
      similar to SDD seen in early human AMD. These mice also develop impaired dark
      adaptation, a cardinal feature of RPE cell dysfunction seen in human AMD patients
      even before central vision is affected. Subretinal deposits in these mice
      progressively worsen with age, with concomitant accumulation of cholesterol
      metabolites including several oxysterols and cholesterol esters causing
      lipotoxicity that manifests as photoreceptor dysfunction and neurodegeneration.
      These findings suggest that impaired macrophage cholesterol transport initiates
      several key elements of early human AMD, demonstrating the importance of systemic
      immunity and aging in promoting disease manifestation. Polymorphisms in genes
      involved with cholesterol transport and homeostasis are associated with a
      significantly higher risk of developing AMD, thus making these studies
      translationally relevant by identifying potential targets for therapy.

PMID- 30185654
TI  - Lipocalin-2 derived from adipose tissue mediates aldosterone-induced renal
      injury.
AB  - Lipocalin-2 is not only a sensitive biomarker, but it also contributes to the
      pathogenesis of renal injuries. The present study demonstrates that adipose
      tissue-derived lipocalin-2 plays a critical role in causing both chronic and
      acute renal injuries. Four-week treatment with aldosterone and high salt after
      uninephrectomy (ANS) significantly increased both circulating and urinary
      lipocalin-2, and it induced glomerular and tubular injuries in kidneys of WT
      mice. Despite increased renal expression of lcn2 and urinary excretion of
      lipocalin-2, mice with selective deletion of lcn2 alleles in adipose tissue
      (Adipo-LKO) are protected from ANS- or aldosterone-induced renal injuries. By
      contrast, selective deletion of lcn2 alleles in kidney did not prevent
      aldosterone- or ANS-induced renal injuries. Transplantation of fat pads from WT
      donors increased the sensitivity of mice with complete deletion of Lcn2 alleles
      (LKO) to aldosterone-induced renal injuries. Aldosterone promoted the urinary
      excretion of a human lipocalin-2 variant, R81E, in turn causing renal injuries in
      LKO mice. Chronic treatment with R81E triggered significant renal injuries in
      LKO, resembling those observed in WT mice following ANS challenge. Taken in
      conjunction, the present results demonstrate that lipocalin-2 derived from
      adipose tissue causes acute and chronic renal injuries, largely independent of
      local lcn2 expression in kidney.

PMID- 30185656
TI  - Induction of antiinflammatory purinergic signaling in activated human iNKT cells.
AB  - Invariant natural killer T (iNKT) cells are activated at sites of local tissue
      injury, or globally during vaso-occlusive episodes of sickle cell disease (SCD).
      Tissue damage stimulates production of CD1d-restricted lipid antigens that
      activate iNKT cells to produce Th1- and Th2-type cytokines. Here, we show that
      circulating iNKT cells in SCD patients express elevated levels of the
      ectonucleoside triphosphate diphosphosphohydrolase, CD39, as well the adenosine
      A2A receptor (A2AR). We also investigated the effects of stimulating cultured
      human iNKT cells on the expression of genes involved in the regulation of
      purinergic signaling. iNKT cell stimulation caused induction of ADORA2A, P2RX7,
      CD38, CD39, ENPP1, CD73, PANX1, and ENT1. Transcription of ADA, which degrades
      adenosine, was reduced. Induction of CD39 mRNA was associated with increased ecto
      ATPase activity on iNKT cells that was blocked by POM1. Exposure of iNKT cells to
      A2AR agonists during stimulation reduced production of IFN-gamma and enhanced
      production of IL-13 and CD39. Based on these findings, we define "purinergic Th2
      type cytokine bias" as an antiinflammatory purinergic response to iNKT cell
      stimulation resulting from changes in the transcription of several genes involved
      in purine release, extracellular metabolism, and signaling.

PMID- 30185658
TI  - Multidimensional assessment of alveolar T cells in critically ill patients.
AB  - Pneumonia represents the leading infectious cause of death in the United States.
      Foxp3+ regulatory T cells promote recovery from severe pneumonia in mice, but T
      cell responses in patients with pneumonia remain incompletely characterized
      because of the limited ability to serially sample the distal airspaces and
      perform multidimensional molecular assessments on the small numbers of recovered
      cells. As T cell function is governed by their transcriptional and epigenetic
      landscape, we developed a method to safely perform high-resolution
      transcriptional and DNA methylation profiling of T cell subsets from the alveoli
      of critically ill patients. Our method involves nonbronchoscopic bronchoalveolar
      lavage combined with multiparameter fluorescence-activated cell sorting,
      unsupervised low-input RNA-sequencing, and a modified reduced-representation
      bisulfite sequencing protocol. Here, we demonstrate the safety and feasibility of
      our method and use it to validate functional genomic elements that were predicted
      by mouse models. Because of its potential for widespread application, our
      techniques allow unprecedented insights into the biology of human pneumonia.

PMID- 30185657
TI  - Ruxolitinib inhibits cyclosporine-induced proliferation of cutaneous squamous
      cell carcinoma.
AB  - Organ transplant recipients (OTRs) on cyclosporine A (CSA) are prone to
      catastrophic cutaneous squamous cell carcinoma (SCC). Allograft-sparing, cancer
      targeting systemic treatments are unavailable. We have shown increased risk for
      catastrophic SCC in OTRs via CSA-mediated induction of IL-22. Herein, we found
      that CSA drives SCC proliferation and tumor growth through IL-22 and JAK/STAT
      pathway induction. We in turn inhibited SCC growth with an FDA-approved JAK1/2
      inhibitor, ruxolitinib. In human SCC cells, the greatest proliferative response
      to IL-22 and CSA treatment occurred in nonmetastasizing lines. IL-22 treatment
      upregulated JAK1 and STAT1/3 in A431 SCC cells. JAK/STAT pathway genes were
      highly expressed in tumors from a cohort of CSA-exposed OTRs and in SCC with high
      risk for metastasis. Compared with immunocompetent SCC, genes associated with
      innate immunity, response to DNA damage, and p53 regulation were differentially
      expressed in SCC from OTRs. In nude mice engrafted with human A431 cells, IL-22
      and CSA treatment increased tumor growth and upregulated IL-22 receptor, JAK1,
      and STAT1/3 expression. Ruxolitinib treatment significantly reduced tumor volume
      and reversed the accelerated tumor growth. CSA and IL-22 exacerbate aggressive
      behavior in SCC. Targeting the IL-22 axis via selective JAK/STAT inhibition may
      reduce the progression of aggressive SCC in OTRs, without compromising
      immunosuppression.

PMID- 30185659
TI  - Calpain-6 controls the fate of sarcoma stem cells by promoting autophagy and
      preventing senescence.
AB  - Sarcomas are still unsolved therapeutic challenges. Cancer stem cells are
      believed to contribute to sarcoma development, but lack of specific markers
      prevents their characterization and targeting. Here, we show that calpain-6
      expression is associated with cancer stem cell features. In mouse models of bone
      sarcoma, calpain-6-expressing cells have unique tumor-initiating and metastatic
      capacities. Calpain-6 levels are especially high in tumors that have been
      successfully propagated in mouse to establish patient-derived xenografts. We
      found that calpain-6 levels are increased by hypoxia in vitro and calpain-6 is
      detected within hypoxic areas in tumors. Furthermore, calpain-6 expression
      depends on the stem cell transcription network that involves Oct4, Nanog, and
      Sox2 and is activated by hypoxia. Calpain-6 knockdown blocks tumor development in
      mouse and induces depletion of the cancer stem cell population. Data from
      transcriptomic analyses reveal that calpain-6 expression in sarcomas inversely
      correlates with senescence markers. Calpain-6 knockdown suppresses hypoxia
      dependent prevention of senescence entry and also promotion of autophagic flux.
      Together, our results demonstrate that calpain-6 identifies sarcoma cells with
      stem-like properties and is a mediator of hypoxia to prevent senescence, promote
      autophagy, and maintain the tumor-initiating cell population. These findings open
      what we believe is a novel therapeutic avenue for targeting sarcoma stem cells.

PMID- 30185660
TI  - 1,25-Dihydroxyvitamin D suppresses M1 macrophages and promotes M2 differentiation
      at bone injury sites.
AB  - An indispensable role of macrophages in bone repair has been well recognized.
      Previous data have demonstrated the copresence of M1 macrophages and mesenchymal
      stem cells (MSCs) during the proinflammatory stage of bone repair. However, the
      exact role of M1 macrophages in MSC function and bone repair is unknown. This
      study aimed to define the role of M1 macrophages at bone injury sites via the
      function of 1,25-Dihydroxyvitamin D (1,25[OH]2D) in suppressing M1 but promoting
      M2 differentiation. We showed that 1,25(OH)2D suppressed M1 macrophage-mediated
      enhancement of MSC migration. Additionally, 1,25(OH)2D inhibited M1 macrophage
      secretion of osteogenic proteins (i.e., Oncostatin M, TNF-alpha, and IL-6).
      Importantly, the 1,25(OH)2D-mediated suppression of osteogenic function in M1
      macrophages at the proinflammatory stage was associated with 1,25(OH)2D-mediated
      reduction of MSC abundance, compromised osteogenic potential of MSCs, and
      impairment of fracture repair. Furthermore, outside the proinflammatory stage,
      1,25(OH)2D treatment did not suppress fracture repair. Accordingly, our data
      support 2 conclusions: (a) M1 macrophages are important for the recruitment and
      osteogenic priming of MSCs and, hence, are necessary for fracture repair, and (b)
      under vitamin D-sufficient conditions, 1,25(OH)2D treatment is unnecessary and
      can be detrimental if provided during the proinflammatory stage of fracture
      healing.

PMID- 30185661
TI  - Large-scale plasma lipidomic profiling identifies lipids that predict
      cardiovascular events in secondary prevention.
AB  - BACKGROUND: Plasma lipidomic measures may enable improved prediction of
      cardiovascular outcomes in secondary prevention. The aim of this study is to
      determine the association of plasma lipidomic measurements with cardiovascular
      events and assess their potential to predict such events. METHODS: Plasma lipids
      (n = 342) were measured in a retrospective subcohort (n = 5,991) of the LIPID
      study. Proportional hazards regression was used to identify lipids associated
      with future cardiovascular events (nonfatal myocardial infarction, nonfatal
      stroke, or cardiovascular death) and cardiovascular death. Multivariable models
      adding lipid species to traditional risk factors were created using lipid ranking
      established from the Akaike information criterion within a 5-fold cross
      validation framework. The results were tested on a diabetic case cohort from the
      ADVANCE study (n = 3,779). RESULTS: Specific ceramide species, sphingolipids,
      phospholipids, and neutral lipids containing omega-6 fatty acids or odd-chain
      fatty acids were associated with future cardiovascular events (106 species) and
      cardiovascular death (139 species). The addition of 7 lipid species to a base
      model (11 conventional risk factors) resulted in an increase in the C-statistics
      from 0.629 (95% CI, 0.628-0.630) to 0.654 (95% CI, 0.653-0.656) for prediction of
      cardiovascular events and from 0.673 (95% CI, 0.671-0.675) to 0.727 (95% CI,
      0.725-0.728) for prediction of cardiovascular death. Categorical net
      reclassification improvements for cardiovascular events and cardiovascular death
      were 0.083 (95% CI, 0.081-0.086) and 0.166 (95% CI, 0.162-0.170), respectively.
      Evaluation on the ADVANCE case cohort demonstrated significant improvement on the
      base models. CONCLUSIONS: The improvement in the prediction of cardiovascular
      outcomes, above conventional risk factors, demonstrates the potential of plasma
      lipidomic profiles as biomarkers for cardiovascular risk stratification in
      secondary prevention. FUNDING: Bristol-Myers Squibb, the National Health and
      Medical Research Council of Australia (grants 211086, 358395, and 1029754), and
      the Operational Infrastructure Support Program of the Victorian government of
      Australia.

PMID- 30185662
TI  - Improved outcomes in PI3K-pathway-altered metastatic HPV oropharyngeal cancer.
AB  - While it has been recognized that human papillomavirus-associated (HPV
      associated) oropharyngeal cancer (OPC) portends an improved prognosis, distinct
      patterns of disease recurrence have emerged. Molecular characterization of this
      subset of HPV patients remains unexplored. We evaluated 52 metastatic HPV+ OPC
      patients from our institution and paired massively parallel sequencing data with
      clinical parameters and survival outcomes in 81% of patients. Genomic data were
      then compared with 2 molecularly defined, curable HPV+ cohorts. Metastatic HPV+
      OPC patients with pulmonary-only metastases demonstrated worse outcomes.
      Nonexclusive somatic alterations in KMT2D and PIK3CA were most frequent, with
      PRKDC alterations occurring at higher frequency when compared with all sequenced
      HPV+ OPC patients. PI3K pathway alterations were associated with improved
      outcomes among metastatic HPV+ OPC patients. We demonstrate subtle differences in
      the mutational landscape between curable and metastatic HPV+ OPC populations,
      with a trend towards more frequent DNA repair protein alterations in the latter.
      We demonstrate improved outcomes when PI3K pathway alterations are present in
      these patients. We provide molecular insights for this important HPV+ subgroup
      that have significant therapeutic implications.

PMID- 30185664
TI  - Polygenic risk score for predicting weight loss after bariatric surgery.
AB  - BACKGROUND: The extent of weight loss among patients undergoing bariatric surgery
      is highly variable. Herein, we tested the contribution of genetic background to
      such interindividual variability after biliopancreatic diversion with duodenal
      switch. METHODS: Percentage of excess body weight loss (%EBWL) was monitored in
      865 patients over a period of 48 months after bariatric surgery, and two
      polygenic risk scores were constructed with 186 and 11 (PRS186 and PRS11) single
      nucleotide polymorphisms previously associated with body mass index (BMI).
      RESULTS: The accuracy of the %EBWL logistic prediction model - including initial
      BMI, age, sex, and surgery modality, and assessed as the area under the receiver
      operating characteristics (ROC) curve adjusted for optimism (AUCadj = 0.867) -
      significantly increased after the inclusion of PRS186 (DeltaAUCadj = 0.021; 95%
      CI of the difference [95% CIdiff] = 0.005-0.038) but not PRS11 (DeltaAUCadj=
      0.008; 95% CIdiff= -0.003-0.019). The overall fit of the longitudinal linear
      mixed model for %EBWL showed a significant increase after addition of PRS186 (-2
      log-likelihood = 12.3; P = 0.002) and PRS11 (-2 log-likelihood = 9.9; P = 0.007).
      A significant interaction with postsurgery time was found for PRS186 (beta = 
      0.003; P = 0.008) and PRS11 (beta = -0.008; P = 0.03). The inclusion of PRS186
      and PRS11 in the model improved the cost-effectiveness of bariatric surgery by
      reducing the percentage of false negatives from 20.4% to 10.9% and 10.2%,
      respectively. CONCLUSION: These results revealed that genetic background has a
      significant impact on weight loss after biliopancreatic diversion with duodenal
      switch. Likewise, the improvement in weight loss prediction after addition of
      polygenic risk scores is cost-effective, suggesting that genetic testing could
      potentially be used in the presurgical assessment of patients with severe
      obesity. FUNDING: Heart and Stroke Foundation of Canada (G-17-0016627) and Canada
      Research Chair in Genomics Applied to Nutrition and Metabolic Health (no. 950-231
      580).

PMID- 30185663
TI  - Targeting CD46 for both adenocarcinoma and neuroendocrine prostate cancer.
AB  - Although initially responsive to androgen signaling inhibitors (ASIs), metastatic
      castration-resistant prostate cancer (mCRPC) inevitably develops and is
      incurable. In addition to adenocarcinoma (adeno), neuroendocrine prostate cancer
      (NEPC) emerges to confer ASI resistance. We have previously combined laser
      capture microdissection and phage antibody display library selection on human
      cancer specimens and identified novel internalizing antibodies binding to tumor
      cells residing in their tissue microenvironment. We identified the target antigen
      for one of these antibodies as CD46, a multifunctional protein that is best known
      for negatively regulating the innate immune system. CD46 is overexpressed in
      primary tumor tissue and CRPC (localized and metastatic; adeno and NEPC), but
      expressed at low levels on normal tissues except for placental trophoblasts and
      prostate epithelium. Abiraterone- and enzalutamide-treated mCRPC cells upregulate
      cell surface CD46 expression. Genomic analysis showed that the CD46 gene is
      gained in 45% abiraterone-resistant mCRPC patients. We conjugated a tubulin
      inhibitor to our macropinocytosing anti-CD46 antibody and showed that the
      resulting antibody-drug conjugate (ADC) potently and selectively kills both adeno
      and NEPC cell lines in vitro (sub-nM EC50) but not normal cells. CD46 ADC
      regressed and eliminated an mCRPC cell line xenograft in vivo in both
      subcutaneous and intrafemoral models. Exploratory toxicology studies of the CD46
      ADC in non-human primates demonstrated an acceptable safety profile. Thus, CD46
      is an excellent target for antibody-based therapy development, which has
      potential to be applicable to both adenocarcinoma and neuroendocrine types of
      mCRPC that are resistant to current treatment.

PMID- 30185666
TI  - Cyclin-dependent kinase 4 is a preclinical target for diet-induced obesity.
AB  - When obesity is caused by consumption of a high-fat diet, the tumor suppressor
      pRb is phosphoinactivated in the neurons of the mediobasal hypothalamus, a brain
      area critical for energy-balance regulation. However, the functional relevance of
      pRb phosphoinactivation in the mediobasal hypothalamus to diet-induced obesity
      remains unknown. Here, we show that inhibiting pRb phosphorylation in the
      mediobasal hypothalamus can prevent and treat diet-induced obesity in mice.
      Expressing an unphosphorylable pRb nonselectively in the mediobasal hypothalamus
      or conditionally in anorexigenic POMC neurons inhibits diet-induced obesity.
      Intracerebroventricular delivery of US Food and Drug Administration-approved (FDA
      approved) cyclin-dependent kinase 4 (CDK4) inhibitor abemaciclib inhibits pRb
      phosphorylation in the mediobasal hypothalamus and prevents diet-induced obesity.
      Oral administration of abemaciclib at doses approved for human use reduces fat
      mass in diet-induced obese mice by increasing lipid oxidation without
      significantly reducing lean mass. With analysis of recent literature identifying
      CDK4 as the most abundantly expressed neuronal CDK in the mediobasal
      hypothalamus, our work uncovers CDK4 as the major kinase for hypothalamic pRb
      phosphoinactivation and a highly effective central antiobesity target. As three
      CDK4/6 inhibitors have recently received FDA approval for life-long breast cancer
      therapy, our study provides a preclinical basis for their expedient repurposing
      for obesity management.

PMID- 30185665
TI  - Two-photon imaging of the mammalian retina with ultrafast pulsing laser.
AB  - Noninvasive imaging of visual system components in vivo is critical for
      understanding the causal mechanisms of retinal diseases and for developing
      therapies for their treatment. However, ultraviolet light needed to excite
      endogenous fluorophores that participate in metabolic processes of the retina is
      highly attenuated by the anterior segment of the human eye. In contrast, 2-photon
      excitation fluorescence imaging with pulsed infrared light overcomes this
      obstacle. Reducing retinal exposure to laser radiation remains a major barrier in
      advancing this technology to studies in humans. To increase fluorescence
      intensity and reduce the requisite laser power, we modulated ultrashort laser
      pulses with high-order dispersion compensation and applied sensorless adaptive
      optics and custom image recovery software and observed an over 300% increase in
      fluorescence of endogenous retinal fluorophores when laser pulses were shortened
      from 75 fs to 20 fs. No functional or structural changes to the retina were
      detected after exposure to 2-photon excitation imaging light with 20-fs pulses.
      Moreover, wide bandwidth associated with short pulses enables excitation of
      multiple fluorophores with different absorption spectra and thus can provide
      information about their relative changes and intracellular distribution. These
      data constitute a substantial advancement for safe 2-photon fluorescence imaging
      of the human eye.

PMID- 30185667
TI  - Mouse model of Gram-negative prosthetic joint infection reveals therapeutic
      targets.
AB  - Bacterial biofilm infections of implantable medical devices decrease the
      effectiveness of antibiotics, creating difficult-to-treat chronic infections.
      Prosthetic joint infections (PJI) are particularly problematic because they
      require prolonged antibiotic courses and reoperations to remove and replace the
      infected prostheses. Current models to study PJI focus on Gram-positive bacteria,
      but Gram-negative PJI (GN-PJI) are increasingly common and are often more
      difficult to treat, with worse clinical outcomes. Herein, we sought to develop a
      mouse model of GN-PJI to investigate the pathogenesis of these infections and
      identify potential therapeutic targets. An orthopedic-grade titanium implant was
      surgically placed in the femurs of mice, followed by infection of the knee joint
      with Pseudomonas aeruginosa or Escherichia coli. We found that in vitro biofilm
      producing activity was associated with the development of an in vivo orthopedic
      implant infection characterized by bacterial infection of the bone/joint tissue,
      biofilm formation on the implants, reactive bone changes, and inflammatory immune
      cell infiltrates. In addition, a bispecific antibody targeting P. aeruginosa
      virulence factors (PcrV and Psl exopolysaccharide) reduced the bacterial burden
      in vivo. Taken together, our findings provide a preclinical model of GN-PJI and
      suggest the therapeutic potential of targeting biofilm-associated antigens.

PMID- 30185668
TI  - Human defects in STAT3 promote oral mucosal fungal and bacterial dysbiosis.
AB  - Studies in patients with genetic defects can provide unique insights regarding
      the role of specific genes and pathways in humans. Patients with defects in the
      Th17/IL-17 axis, such as patients harboring loss-of-function STAT3 mutations
      (autosomal-dominant hyper IgE syndrome; AD-HIES) present with recurrent oral
      fungal infections. Our studies aimed to comprehensively evaluate consequences of
      STAT3 deficiency on the oral commensal microbiome. We characterized fungal and
      bacterial communities in AD-HIES in the presence and absence of oral fungal
      infection compared with healthy volunteers. Analyses of oral mucosal fungal
      communities in AD-HIES revealed severe dysbiosis with dominance of Candida
      albicans (C. albicans) in actively infected patients and minimal representation
      of health-associated fungi and/or opportunists. Bacterial communities also
      displayed dysbiosis in AD-HIES, particularly in the setting of active Candida
      infection. Active candidiasis was associated with decreased microbial diversity
      and enrichment of the streptococci Streptococcus oralis (S. oralis) and S.
      mutans, suggesting an interkingdom interaction of C. albicans with oral
      streptococci. Increased abundance of S. mutans was consistent with susceptibility
      to dental caries in AD-HIES. Collectively, our findings illustrate a critical
      role for STAT3/Th17 in the containment of C. albicans as a commensal organism and
      an overall contribution in the establishment of fungal and bacterial oral
      commensal communities.

PMID- 30185669
TI  - Gestational diabetes and maternal obesity are associated with epigenome-wide
      methylation changes in children.
AB  - Offspring of women with gestational diabetes mellitus (GDM) are at increased risk
      of developing metabolic disease, potentially mediated by epigenetic mechanisms.
      We recruited 608 GDM and 626 control offspring from the Danish National Birth
      Cohort, aged between 9 and 16 years. DNA methylation profiles were measured in
      peripheral blood of 93 GDM offspring and 95 controls using the Illumina
      HumanMethylation450 BeadChip. Pyrosequencing was performed for
      validation/replication of putative GDM-associated, differentially methylated CpGs
      in additional 905 offspring (462 GDM, 444 control offspring). We identified 76
      differentially methylated CpGs in GDM offspring compared with controls in the
      discovery cohort (FDR, P < 0.05). Adjusting for offspring BMI did not affect the
      association between methylation levels and GDM status for any of the 76 CpGs.
      Most of these epigenetic changes were due to confounding by maternal prepregnancy
      BMI; however, 13 methylation changes were independently associated with maternal
      GDM. Three prepregnancy BMI-associated CpGs (cg00992687 and cg09452568 of ESM1
      and cg14328641 of MS4A3) were validated in the replication cohort, while
      cg09109411 (PDE6A) was found to be associated with GDM status. The identified
      methylation changes may reflect developmental programming of organ disease
      mechanisms and/or may serve as disease biomarkers.

PMID- 30185671
TI  - MEG3 is increased in idiopathic pulmonary fibrosis and regulates epithelial cell
      differentiation.
AB  - Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease
      causing fibrotic remodeling of the peripheral lung, leading to respiratory
      failure. Peripheral pulmonary epithelial cells lose normal alveolar epithelial
      gene expression patterns and variably express genes associated with diverse
      conducting airway epithelial cells, including basal cells. Single-cell RNA
      sequencing of pulmonary epithelial cells isolated from IPF lung tissue
      demonstrated altered expression of LncRNAs, including increased MEG3. MEG3 RNA
      was highly expressed in subsets of the atypical IPF epithelial cells and
      correlated with conducting airway epithelial gene expression patterns. Expression
      of MEG3 in human pulmonary epithelial cell lines increased basal cell-associated
      RNAs, including TP63, KRT14, STAT3, and YAP1, and enhanced cell migration,
      consistent with a role for MEG3 in regulating basal cell identity. MEG3 reduced
      expression of TP73, SOX2, and Notch-associated RNAs HES1 and HEY1, in primary
      human bronchial epithelial cells, demonstrating a role for MEG3 in the inhibition
      of genes influencing basal cell differentiation into club, ciliated, or goblet
      cells. MEG3 induced basal cell genes and suppressed genes associated with
      terminal differentiation of airway cells, supporting a role for MEG3 in
      regulation of basal progenitor cell functions, which may contribute to tissue
      remodeling in IPF.

PMID- 30185672
TI  - Excessive localized leukotriene B4 levels dictate poor skin host defense in
      diabetic mice.
AB  - Poorly controlled diabetes leads to comorbidities and enhanced susceptibility to
      infections. While the immune components involved in wound healing in diabetes
      have been studied, the components involved in susceptibility to skin infections
      remain unclear. Here, we examined the effects of the inflammatory lipid mediator
      leukotriene B4 (LTB4) signaling through its receptor B leukotriene receptor 1
      (BLT1) in the progression of methicillin-resistant Staphylococcus aureus (MRSA)
      skin infection in 2 models of diabetes. Diabetic mice produced higher levels of
      LTB4 in the skin, which correlated with larger nonhealing lesion areas and
      increased bacterial loads compared with nondiabetic mice. High LTB4 levels were
      also associated with dysregulated cytokine and chemokine production, excessive
      neutrophil migration but impaired abscess formation, and uncontrolled collagen
      deposition. Both genetic deletion and topical pharmacological BLT1 antagonism
      restored inflammatory response and abscess formation, followed by a reduction in
      the bacterial load and lesion area in the diabetic mice. Macrophage depletion in
      diabetic mice limited LTB4 production and improved abscess architecture and skin
      host defense. These data demonstrate that exaggerated LTB4/BLT1 responses mediate
      a derailed inflammatory milieu that underlies poor host defense in diabetes.
      Prevention of LTB4 production/actions could provide a new therapeutic strategy to
      restore host defense in diabetes.

PMID- 30185673
TI  - Guaiacol as a drug candidate for treating adult polyglucosan body disease.
AB  - Adult polyglucosan body disease (APBD) is a late-onset disease caused by
      intracellular accumulation of polyglucosan bodies, formed due to glycogen
      branching enzyme (GBE) deficiency. To find a treatment for APBD, we screened
      1,700 FDA-approved compounds in fibroblasts derived from APBD-modeling GBE1
      knockin mice. Capitalizing on fluorescent periodic acid-Schiff reagent, which
      interacts with polyglucosans in the cell, this screen discovered that the
      flavoring agent guaiacol can lower polyglucosans, a result also confirmed in APBD
      patient fibroblasts. Biochemical assays showed that guaiacol lowers basal and
      glucose 6-phosphate-stimulated glycogen synthase (GYS) activity. Guaiacol also
      increased inactivating GYS1 phosphorylation and phosphorylation of the master
      activator of catabolism, AMP-dependent protein kinase. Guaiacol treatment in the
      APBD mouse model rescued grip strength and shorter lifespan. These treatments had
      no adverse effects except making the mice slightly hyperglycemic, possibly due to
      the reduced liver glycogen levels. In addition, treatment corrected penile
      prolapse in aged GBE1-knockin mice. Guaiacol's curative effects can be explained
      by its reduction of polyglucosans in peripheral nerve, liver, and heart, despite
      a short half-life of up to 60 minutes in most tissues. Our results form the basis
      to use guaiacol as a treatment and prepare for the clinical trials in APBD.

PMID- 30185670
TI  - The complex landscape of microRNAs in articular cartilage: biology, pathology,
      and therapeutic targets.
AB  - The disabling degenerative disease osteoarthritis (OA) is prevalent among the
      global population. Articular cartilage degeneration is a central feature of OA;
      therefore, a better understanding of the mechanisms that maintain cartilage
      homeostasis is vital for developing effective therapeutic interventions.
      MicroRNAs (miRs) modulate cell signaling pathways and various processes in
      articular cartilage via posttranscriptional repression of target genes. As
      dysregulated miRs frequently alter the homeostasis of articular cartilage,
      modulating select miRs presents a potential therapeutic opportunity for OA. Here,
      we review key miRs that have been shown to modulate cartilage-protective or 
      destructive mechanisms and signaling pathways. Additionally, we use an
      integrative computational biology approach to provide insight into predicted miR
      gene targets that may contribute to OA pathogenesis, and highlight the complexity
      of miR signaling in OA by generating both unique and overlapping gene targets of
      miRs that mediate protective or destructive effects. Early OA detection would
      enable effective prevention; thus, miRs are being explored as diagnostic
      biomarkers. We discuss these ongoing efforts and the applicability of miR mimics
      and antisense inhibitors as potential OA therapeutics.

PMID- 30185674
TI  - Attached stratified mucus separates bacteria from the epithelial cells in COPD
      lungs.
AB  - The respiratory tract is normally kept essentially free of bacteria by cilia
      mediated mucus transport, but in chronic obstructive pulmonary disease (COPD) and
      cystic fibrosis (CF), bacteria and mucus accumulates instead. To address the
      mechanisms behind the mucus accumulation, the proteome of bronchoalveolar lavages
      from COPD patients and mucus collected in an elastase-induced mouse model of COPD
      was analyzed, revealing similarities with each other and with the protein content
      in colonic mucus. Moreover, stratified laminated sheets of mucus were observed in
      airways from patients with CF and COPD and in elastase-exposed mice. On the other
      hand, the mucus accumulation in the elastase model was reduced in Muc5b-KO mice.
      While mucus plugs were removed from airways by washing with hypertonic saline in
      the elastase model, mucus remained adherent to epithelial cells. Bacteria were
      trapped on this mucus, whereas, in non-elastase-treated mice, bacteria were found
      on the epithelial cells. We propose that the adherence of mucus to epithelial
      cells observed in CF, COPD, and the elastase-induced mouse model of COPD
      separates bacteria from the surface cells and, thus, protects the respiratory
      epithelium.

PMID- 30185675
TI  - Belimumab promotes negative selection of activated autoreactive B cells in
      systemic lupus erythematosus patients.
AB  - Belimumab has therapeutic benefit in active systemic lupus erythematosus (SLE),
      especially in patients with high-titer anti-dsDNA antibodies. We asked whether
      the profound B cell loss in belimumab-treated SLE patients is accompanied by
      shifts in the immunoglobulin repertoire. We enrolled 15 patients who had been
      continuously treated with belimumab for more than 7 years, 17 matched controls,
      and 5 patients who were studied before and after drug initiation. VH genes of
      sort-purified mature B cells and plasmablasts were subjected to next-generation
      sequencing. We found that B cell-activating factor (BAFF) regulates the
      transitional B cell checkpoint, with conservation of transitional 1 (T1) cells
      and approximately 90% loss of T3 and naive B cells after chronic belimumab
      treatment. Class-switched memory B cells, B1 B cells, and plasmablasts were also
      substantially depleted. Next-generation sequencing revealed no redistribution of
      VH, DH, or JH family usage and no effect of belimumab on representation of the
      autoreactive VH4-34 gene or CDR3 composition in unmutated IgM sequences,
      suggesting a minimal effect on selection of the naive B cell repertoire.
      Interestingly, a significantly greater loss of VH4-34 was observed among mutated
      IgM and plasmablast sequences in chronic belimumab-treated subjects than in
      controls, suggesting that belimumab promotes negative selection of activated
      autoreactive B cells.

PMID- 30185676
TI  - Nicotinamide mononucleotide preserves mitochondrial function and increases
      survival in hemorrhagic shock.
AB  - Hemorrhagic shock depletes nicotinamide adenine dinucleotide (NAD) and causes
      metabolic derangements that, in severe cases, cannot be overcome, even after
      restoration of blood volume and pressure. However, current strategies to treat
      acute blood loss do not target cellular metabolism. We hypothesized that
      supplemental nicotinamide mononucleotide (NMN), the immediate biosynthetic
      precursor to NAD, would support cellular energetics and enhance physiologic
      resilience to hemorrhagic shock. In a rodent model of decompensated hemorrhagic
      shock, rats receiving NMN displayed significantly reduced lactic acidosis and
      serum IL-6 levels, two strong predictors of mortality in human patients. In both
      livers and kidneys, NMN increased NAD levels and prevented mitochondrial
      dysfunction. Moreover, NMN preserved mitochondrial function in isolated
      hepatocytes cocultured with proinflammatory cytokines, indicating a cell
      autonomous protective effect that is independent from the reduction in
      circulating IL-6. In kidneys, but not in livers, NMN was sufficient to prevent
      ATP loss following shock and resuscitation. Overall, NMN increased the time
      animals could sustain severe shock before requiring resuscitation by nearly 25%
      and significantly improved survival after resuscitation (P = 0.018), whether NMN
      was given as a pretreatment or only as an adjunct during resuscitation. Thus, we
      demonstrate that NMN substantially mitigates inflammation, improves cellular
      metabolism, and promotes survival following hemorrhagic shock.

PMID- 30185678
TI  - Sonographic assessment of urolithiasis in University of Abuja Teaching Hospital,
      Nigeria.
AB  - Background: Urolithiasis may result in many complications including renal
      failure. There is a paucity of documented scientific study on the prevalence of
      urolithiasis in the University of Abuja Teaching Hospital within the Federal
      Capital Territory, Nigeria. The aim of the study was to assess the prevalence of
      urolithiasis in patients undergoing ultrasound at University of Abuja Teaching
      Hospital. Materials and Methods: This study which adopted a survey approach was
      conducted at the Department of Radiology, University of Abuja Teaching Hospital
      between June 2014 and May 2015. A total of 2310 patients that underwent
      abdominopelvic ultrasound in the department who aged between 2 and 64 years and
      met the inclusion criteria participated in the study. They were recruited using a
      convenience (nonprobability) sampling technique. Data obtained were subjected to
      descriptive statistics and analyzed using Student's t-test. P < 0.05 was
      considered statistically significant. Results: A total of 2310 patients were
      scanned, 31 patients were sonographically identified with urolithiasis. The
      prevalence of urolithiasis was 13.4/1000. The mean age was 31.12 +/- 3.69 years.
      There were 58.06% males and 41.93% females giving a male-to-female ratio of
      1.3:1. The peak age of incidence was 21-50 years. Majority (22 [71%]) were
      located in the upper urinary tract, whereas 9 (27%) were in the lower urinary
      tract. The most common presenting symptoms were flank/loin pains (renal colic)
      noted in 12 (40%) patients, followed by hematuria in 4 (13.3%) patients.
      Conclusion: The prevalence of urolithiasis was 13.4/1000. This information can be
      utilized in formulating future health plans for prevention of urolithiasis in the
      hospitals within this locality.

PMID- 30185677
TI  - A review of bladder cancer in Sub-Saharan Africa: A different disease, with a
      distinct presentation, assessment, and treatment.
AB  - Background: Cancer of the bladder is the ninth leading cause of cancer in
      developed countries. It is the second most common urological malignancy.
      Transitional cell carcinoma (TCC) is the most common histological subtype in
      developed countries. In most of Africa, the most common type is squamous cell
      carcinoma (SCC). Cancer of bladder guidelines produced by the European Urological
      Association and the American Urological Association, including the tumor, node,
      and metastasis staging is focused on TCC of the bladder. Objectives: The purpose
      of the study is to review the pathogenesis, pathology, presentation, and
      management of cancer of the bladder in Africa and to use this information to
      propose a practical staging system for SCC. Methods: The study used the meta
      analysis guideline provided by PRISMA using bladder cancer in Africa as the key
      search word. The study collected articles available on PubMed as of July 2017,
      Africa Online and Africa Index Medicus. PRISMA guidelines were used to screen for
      full-length hospital-based articles on cancer of the bladder in Africa. These
      articles were analyzed under four subcategories which were pathogenesis,
      pathology, clinical presentation, and management. The information extracted was
      pooled and used to propose a practical staging system for use in African
      settings. Results: The result of evaluation of 821 articles yielded 23 full
      length papers on hospital-based studies of cancer of the bladder in Africa.
      Cancer of the bladder in most of Africa is still predominantly SCC (53%-69%).
      There has been a notable increase in TCC in Africa (9%-41%). The pathogenesis is
      mostly schistosoma-related SCC presents late with painful hematuria and
      necroturia (20%). SCC responds poorly to chemotherapy or radiotherapy. The main
      management of SCC is open surgery. This review allowed for a practical organ
      based stage of SCC of the bladder that can be used in Africa. Conclusion: Bladder
      cancer in Africa presents differently from that in developed countries.
      Guidelines on cancer of the bladder may need to take account of this to improve
      bladder cancer management in Africa.

PMID- 30185679
TI  - Antibiotic susceptibility of wound swab isolates in a tertiary hospital in
      Southwest Nigeria.
AB  - Background: Wounds are commonly encountered in the clinical practice.
      Microbacterial colonization and infection negatively affect wound outcomes. With
      increasing emergence of antibiotic-resistant strains, it is essential to
      determine local patterns of wound microbiological profile and antibiotic
      susceptibility to guide rational empirical antibiotic use. Materials and Methods:
      Consecutive patients who presented to the plastic surgery unit were recruited to
      the study over a 6-month period. Wound swab cultures were performed at
      presentation using standard protocols and media. The wound swab was performed by
      the Levine technique and data were analyzed using a statistical software package.
      Results: Eighty-five microbial isolates were obtained from the eighty patients
      (55 males and 25 females) recruited. Gram-positive isolates were 35 (41.2%) and
      Gram-negative were 50 (58.8%). There was equal distribution of acute and chronic
      wounds. Pseudomonas aeruginosa was the most common isolate at 30.6%, followed by
      Staphylococcus aureus (27.1%), Escherichia coli (9.4%), Streptococcus species
      (8.2%), and Morganella morganii (7.1%). The isolates demonstrated resistance to
      amoxicillin-clavulanate, ampicillin, cloxacillin, cefuroxime, ceftazidime; low-to
      moderate sensitivity to erythromycin, gentamicin, streptomycin, tetracycline,
      ciprofloxacin, and ofloxacin; and a moderate sensitivity to ceftriaxone and a
      high sensitivity to imipenem. There was significant difference in antibiotic
      resistance patterns between Gram-positive isolates from acute and chronic wound
      infections but not for acute and chronic wound Gram-negative isolates.
      Conclusion: Most of the microbial isolates, particularly the Gram-negative
      isolates demonstrated low sensitivity to commonly used antibiotics and moderate
      to-high sensitivity to less commonly used newer antibiotics.

PMID- 30185680
TI  - Role of high resolution ultrasound complementary to digital mammography.
AB  - Background: Breast carcinoma is a major cause of mortality among women worldwide.
      Early detection and cure is the key to reduce the mortality of the disease. This
      article studied the role of high resolution ultrasound in detection and
      characterization of lesions to complement mammographic diagnosis and improve
      patient management. Aims and Objectives: To evaluate the role of complementary
      high resolution ultrasound, BIRADS scoring and to correlate it with histological
      diagnosis. Results and Observations: HRUS is excellent in detecting
      microcalcifications, malignant features of solid masses, differentiating focal
      asymmetry from masses, differentiating between solid and cystic lesions, simple
      and complex cysts and detecting satellite lesions and mammographically
      inaccessible areas for which special views can be done. Conclusions: Every case
      referred for digital mammography should undergo ultrasound irrespective of the
      age, symptoms and density of the breast parenchyma and a combined final BIRADS
      grading should be done. Ultrasound is an excellent imaging modality for breast
      lesions in expert hands.

PMID- 30185681
TI  - Prevalence and factors associated with the use of traditional medicines among
      human immunodeficiency virus and acquired immunodeficiency syndrome patients in
      Sokoto, Nigeria.
AB  - Background: In resource-scarce settings like Nigeria, access to conventional
      drugs and antiretroviral therapy (ART) is highly limited, hence the resort to use
      of traditional herbal medicine by a significant number of people living with
      human immunodeficiency virus and acquired immunodeficiency syndrome (HIV/AIDS)
      (PLWHAs). Traditional medicine (TM) continues to provide health coverage for most
      of the people in developing countries, and it is equally becoming increasingly
      popular in western countries. Aim: This study aims to present the status and use
      of TM and determine the factors associated with its use among patients with
      HIV/AIDS on highly active ART in a tertiary health institution in Sokoto,
      Northwest Nigeria. Methodology: This was a descriptive, cross-sectional study
      involving HIV/AIDS patients attending antiretroviral treatment center of the
      Usmanu Danfodiyo University Teaching Hospital (UDUTH), Sokoto, Nigeria. The study
      population comprised PLWHAs attending the ART clinic of the hospital (UDUTH). A
      total of 271 respondents were recruited into the study and administered a set of
      pretested structured questionnaire. Ethical approval for this study was obtained
      from the ethical committee of the teaching hospital. Results: Only 11 (4.2%) of
      the respondents had used TM before, of whom 9 (5%) were females and 2 (2.7%) were
      males with P = 0.399. Only one of the respondents had side effects following the
      use of TM, and the most common reason for the use of TM was as a result of too
      much weight loss. Conclusion: Although the use of TM among the study participants
      in Sokoto was low, there is need to educate PLWHAs about the possible risks of
      interactions following the concurrent use of TM and ART.

PMID- 30185683
TI  - Effectiveness of postoperative analgesia in the management of acute pain in day
      case surgeries.
AB  - Background: Surgery is the most common source of acute pain. Aim: To determine
      the intensity of acute pain following day case surgery and evaluate the
      effectiveness of the prescribed analgesics. Methods: A descriptive observational
      study carried out at the main operating and the Urology Outpatient theatre suites
      of the University College Hospital, Ibadan. Seventy consecutive adult patients
      presenting for day case surgeries between July and September 2013 were recruited.
      The procedures were stratified as follows: peripheral, groin/perineal,
      urologic/endoscopy or orthopedic/plastic surgeries. The prescribed postoperative
      oral analgesics were paracetamol alone or in combination with diclofenac,
      tramadol or both. Postoperative pain intensity was assessed on arrival in the
      recovery room and at 6, 12, 24, 48, & 72 hours using the Verbal Intensity Pain
      Scale (VIPS). The pain scores were presented as mean+/-SD at different time
      intervals for each stratified surgical procedures and analgesics using tables and
      frequency bar charts. A mean pain score of less than 2 for each category of
      surgical procedures or analgesics group was considered as satisfactory pain
      control and thus effective analgesia. Result: The overall prevalence of moderate
      to worst possible pain after surgery in this study was 54.3% on arrival in the
      recovery room. The mean pain score was greater than 2 at 6 hours postoperative in
      all surgical categories except in patients who had peripheral surgeries
      irrespective of single or combination analgesic therapy. Conclusion: A high
      proportion of patients arrived in the recovery room with a high pain score;
      measures to improve intraoperative analgesia should be employed.

PMID- 30185682
TI  - Correlating possible predisposing demographics and systemic conditions with the
      aortic root.
AB  - Background: The aortic root is an aggregate of various components that connects
      the left ventricle to the aorta. The most predominant pathologies have been
      associated with the dilation of the aortic root leading to aneurysms. Aim: This
      study is designed to measure the role of systemic morbidities such as
      hypertension, diabetes, and body mass index (BMI) on the dimension of the aortic
      root. Materials and Methods: Participants were volunteers of African descent who
      were recruited during and after an organized health fair by the medical students'
      body from All Saints University, School of Medicine. 169 participants consisting
      of 62 males and 107 females with ages ranging from 9 to 84 years agreed to
      volunteer by signing the consent after which a questionnaire was administered and
      a preliminary clinical procedure was used to check for blood pressure (BP), blood
      glucose (BG), and BMI. The measurement of the aortic root was carried out by an
      experienced single investigator who was not aware of the purpose of measurements,
      using a DUS-5000 ultrasound machine (Miami, Florida, USA) at a low-frequency
      micro-convex transducer preset to "adult cardiac" with a default frequency of 4
      MHz. Results: Among the participants, 35.03%, 47.80%, and 29.11% had normal BP,
      BG, and BMI readings, respectively. The Chi-squared analysis identified a
      significant correlation between the diameter of the aortic annulus (AA) and BMI.
      Diastolic BP is also correlated with the diameter of the AA. Sinus of Valsalva
      (SV) showed an unusual correlation with BG as opposed to BP and BMI. Conclusion:
      The disparity in how a systemic factor individually correlates with the AA and
      the SV is not clear. The study targets to provide educational concept in this
      regard.

PMID- 30185684
TI  - Outcome of vaginal birth after cesarean section: A retrospective comparative
      analysis of spontaneous versus induced labor in women with one previous cesarean
      section.
AB  - Objective: The purpose of this study is to compare the success rate of vaginal
      birth after cesarean (VBAC) in spontaneous and induced labor. Design: This is an
      8-year retrospective comparative study. Setting: University hospital. Population:
      Five hundred and ninety-four women who had one previous lower segment cesarean
      delivery. Materials and Methods: This is a retrospective study of all women, who
      had lower segment cesarean section, admitted for trial of labor between April
      2010 and November 2016. Five hundred and sixty-seven women who elected to have
      trial of labor after one previous cesarean were included in the study, of these
      477 (84.13%) had spontaneous onset of labor (control group) and 90 (15.87%) had
      induction of labor (IOL) (study group). Two hundred and seventy-seven women had
      no previous vaginal delivery, and 297 had one previous vaginal delivery. Results:
      We compared the success rates of VBAC in women who had IOL with those who came
      with spontaneous labor. The rate of vaginal delivery after CS (VBAC) was 50.0%
      and 66.6% in the study and control groups, respectively. There was a significant
      increase in the rate of cesarean delivery due to fetal distress in the study
      group (P = 0.016). There were no cases of uterine rupture in the control group
      and one case in the study group. Patients who had spontaneous labor and at least
      one previous vaginal delivery have higher success rate of vaginal delivery.
      Conclusion: Women with one previous CS, who undergo IOL, have lower success rates
      of vaginal delivery compared with those who presented in spontaneous labor. They
      also have higher risk of CS delivery due to fetal distress. Previous normal
      vaginal delivery increases the success rate of VBAC.

PMID- 30185685
TI  - Clinical pattern and antibiotic sensitivity of bacterial corneal ulcers in Kano,
      Northern Nigeria.
AB  - Purpose: The purpose of this study is to determine predisposing factors, common
      bacterial causes, and antibiotic sensitivity of corneal ulcers in Murtala
      Muhammad Specialist Hospital. Materials and Methods: A prospective, cross
      sectional, observational study was carried out on patients with corneal ulcers.
      Information on relevant clinical, sociodemographic profile was obtained.
      Examination includes visual acuity test and slit-lamp biomicroscopy, especially
      fluorescein staining. Corneal scrapings from the ulcer were inoculated onto the
      selected solid culture media plates. Gram staining for microscopic examination
      was done. Antibiotic sensitivity test on different antibiograms was done using
      modified Kirby-Bauer technique, determining bacterial isolate sensitivity or
      resistance to relevant antibiotics (chloramphenicol, ciprofloxacin, ofloxacin,
      gentamicin, tetracycline, ceftazidime, ceftriaxone, cefotaxime, and penicillin).
      Results: A total of 77 patients with corneal ulcer were examined. Ocular trauma,
      application of harmful traditional eye medication, and use of unspecified topical
      medication before presentation were among the predisposing factors. Bacterial
      growth was seen in 46.8% of the samples, of which 28.6% of the growth were Gram
      positive. The common bacteria isolated were Staphylococcus epidermidis,
      Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pneumoniae, Proteus
      species, and Klebsiella pneumoniae. Isolates were sensitive to ciprofloxacin and
      ofloxacin while an intermediate sensitivity was seen with chloramphenicol and
      gentamicin. Isolates were resistant to tetracycline, ceftazidime, ceftriaxone,
      cefotaxime, and penicillin. Conclusion: Ocular trauma was the major predisposing
      factor to corneal ulcer, and Staphylococcus species was the major bacterial
      organism isolated. Isolates were found to be sensitive to ciprofloxacin and
      ofloxacin, while an intermediate sensitivity was seen with chloramphenicol and
      gentamicin.

PMID- 30185686
TI  - Poststroke emotionalism with dacrystic (Crying) episodes - making a case for
      risperidone.
AB  - Emotionalism is the abnormal expression of emotions like crying and laughing and
      could follow stroke, traumatic brain injury, multiple sclerosis and amyotrophic
      lateral sclerosis. Emotionalism has been known to respond therapeutically to
      different classes of drugs including tricyclic antidepressants like imipramine,
      Selective Serotonin Reuptake Inhibitors (SSRI) like sertraline and citalopram,
      anticonvulsants like lamotrigine, dopamine precursors like levodopa and NMDA
      receptor antagonists like dextromethorphan. Classical antipsychotics are hardly
      prescribed for emotionalism alone without psychotic features. In this case
      report, an eighty year old woman with a dominant fronto-temporal infarctive
      stroke with right faciohemiparesis presented with frequent crying (dacrystic)
      episodes after a month of onset of stroke and who did not satisfy DSM IV criteria
      for depression nor had other psychotic features. Serial trial of SSRIs and
      dextromethorphan/quinidine could not help until risperidone, an antipsychotic was
      introduced with resolution of crying episodes. The response to risperidone after
      trial of SSRIs and dextromethorphan/quinidine which are considered the gold
      standard for post-stroke emotionalism (PSE), could be another therapeutic
      dimension in the management of emotionalism in general and PSE in particular.

PMID- 30185687
TI  - Shobowale EO, Solarin AU, Elikwu CJ, Onyedibe KI, Akinola IJ, Faniran AA.
      Neonatal sepsis in a Nigerian private tertiary hospital: Bacterial isolates, risk
      factors, and antibiotic susceptibility patterns. Ann Afr Med 2017;16:52-8.

PMID- 30185688
TI  - Erratum: Acute ischemic stroke thrombolysis with tenecteplase: An institutional
      experience from South India.
AB  - [This corrects the article DOI: 10.4103/aam.aam_50_17].

PMID- 30185689
TI  - Clonal Hematopoiesis and Its Impact on Cardiovascular Disease.
AB  - A number of recent epidemiological studies have associated the clonal expansion
      of hematopoietic cells, a process referred to as clonal hematopoiesis, with
      increased mortality. Clonal hematopoiesis increases the risk of hematological
      cancer, but this overall risk cannot account for the increase in mortality in the
      general population. Surprisingly, these mutations have also been associated with
      higher rates of cardiovascular disease, suggesting a previously unrecognized link
      between somatic mutations in hematopoietic cells and chronic disease. Here, we
      review recent epidemiological and experimental studies on clonal hematopoiesis
      that relate to cardiovascular disease.

PMID- 30185690
TI  - Transthyretin Stabilizer Is Associated With Expanding Apical Sparing Area and
      Improving Global Cardiac Function in a Patient With Wild-Type Cardiac
      Amyloidosis.

PMID- 30185691
TI  - Epicardial Fat and Pericardial Fat Surrounding the Heart Have Different
      Characteristics.

PMID- 30185692
TI  - More Benefits From Endovascular Thrombectomy in Patients With Atrial
      Fibrillation?

PMID- 30185693
TI  - Prenatal bisphenol A exposure is associated with medial amygdala neuron
      hyperresponsiveness to predator odor in rats.
AB  - Perinatal exposure to bisphenol A (BPA) causes several alterations in brain
      function and behavior. In previous studies, we showed that prenatal treatment
      with low-level BPA impaired gender-specific behavior, enhanced depression-like
      behavior, and augmented behavioral responses to predator odor in rats. On this
      premise, we hypothesized that BPA-treated rats were more susceptible to predator
      odor stress. To test the potential neural mechanism underlying this effect, we
      conducted an electrophysiological study of neurons in the medial amygdala-a
      regional component of the olfactory pathway with high estrogen and androgen
      receptor expression, and thus a potential target of BPA-in rats exposed to BPA.
      Extracellular recordings were obtained during the presentation of 3 plant odors
      and 3 predator odorants. Odor-responsive neurons in BPA-exposed rats showed
      greater activity in response to fox odor than did those in control rats. This
      finding complements the results of our previous behavioral study in which BPA
      exposed rats exhibited enhanced avoidance behavior in response to fox odor. Given
      the close relationship between olfactory signaling and the stress response
      system, we suspect that BPA modifies the olfactory pathway at the level of the
      medial amygdala and thus modulates the corresponding stress response.

PMID- 30185694
TI  - Cadmium down-regulates apolipoprotein E (ApoE) expression during malignant
      transformation of rat liver cells: direct evidence for DNA hypermethylation in
      the promoter region of ApoE.
AB  - There is adequate evidence for the carcinogenicity of cadmium (Cd). However, a
      significant unaddressed question remains as to how this metal actually causes
      malignant transformation (tumor initiation). Since it has been shown that Cd only
      has the weak direct interaction potential with DNA, the metal is recognized as an
      indirect genotoxicant and mutagen. Currently, Cd-mediated "epigenetic"
      modifications, such as changes in DNA methylation resulting in alteration in
      target gene expression, coupled with cancer progression, are the focus of
      mechanistic research. We have reported that the apolipoprotein E (ApoE) gene, a
      suppressor of cell invasion, is an early Cd target, and is involved in the
      malignant transformation of TRL 1215 rodent liver cells. Cd exposure suppresses
      ApoE expression which can be re-activated with 5-aza-2'-deoxycytidine, a DNA
      demethylating agent. In the present study, we sought direct evidence of Cd
      induced DNA hypermethylation of the ApoE promoter region by performing bisulfite
      sequencing and real-time quantitative methylation-specific PCR. Our data clearly
      suggest that Cd can down-regulate the expression of ApoE via introduction of
      excess DNA methylation in the promoter region of ApoE during malignant
      transformation of TRL 1215 cells.

PMID- 30185696
TI  - Verification of a false positive in a two-year rat carcinogenicity study using
      dual control groups.
AB  - There is sometimes controversy over whether or not statistically significant
      responses produced in carcinogenicity studies have biologically significance.
      Ambiguous results from our previous two-year oral carcinogenicity study on
      acotiamide hydrochloride hydrate (acotiamide-HH), a prokinetic drug for
      functional dyspepsia, in rats made it unclear whether the drug may exhibit
      uterine carcinogenicity. To check this finding, we performed a second long-term
      carcinogenicity study using two identical control groups to more accurately
      evaluate uterine carcinogenesis by considering the incidence of spontaneous
      neoplasms. Female Fischer 344 rats were divided into three groups: the two
      control groups (control 1 and 2) were administered vehicle (0.5% w/v
      methylcellulose) and the acotiamide-HH-treated group was administered 2,000
      mg/kg/day of acotiamide-HH by oral gavage for two years. Among all groups, the
      incidence of endometrial adenocarcinoma (EmA) was highest in the control 2 group,
      followed by the acotiamide-HH-treated group and the control 1 group. Moreover,
      acotiamide-HH did not affect the incidence of precursor lesions of EmA. In cases
      where an ambiguous difference is observed, the use of two control groups allows
      for a more informed interpretation of the findings in the drug-treated groups.
      The outcomes in this study strongly support the hypothesis that the increase in
      EmA in rats treated with acotiamide-HH in our previous study is unrelated to
      administration of the drug.

PMID- 30185695
TI  - MnTMPyP inhibits paraquat-induced pulmonary epithelial-like cell injury by
      inhibiting oxidative stress.
AB  - OBJECTIVE: To investigate the protective effect and underlying mechanism of the
      superoxide dismutase mimic, manganese (III) tetrakis (1-methyl-4-pyridyl)
      porphyrin pentachloride (MnTMPyP), on paraquat (PQ)-induced lung alveolar
      epithelial-like cell injury. METHODS: Lung alveolar epithelial-like cells (A549)
      were pretreated with 10 MUM MnTMPyP for 1.5 hr and then cultured with or without
      PQ (750 uM) for 24 hr. Cell survival was determined using the MTT assay.
      Apoptosis, mitochondrial transmembrane potential, reactive oxygen species (ROS)
      production, and Ca2+ levels were measured using flow cytometry. Glutathione
      reductase activity (GR activity) and caspase-3 activation were determined using
      spectrophotometry. Expression of the apoptosis proteins, Bcl-2 and Bax, and the
      endoplasmic reticulum (ER) stress proteins, glucose regulatory protein 78 (Grp78)
      and C/EBP homologous protein (CHOP), was measured using Western blot analysis.
      RESULTS: Cell viability, mitochondrial membrane potential, GR activity, and Bcl-2
      expression were decreased, but apoptosis, ROS production, caspase-3 activity,
      cytoplasmic Ca2+ levels, and Bax, Grp78 and CHOP expression were all increased in
      the PQ group compared to the control group. There were no statistically
      significant changes in the MnTMPyP group. Cell viability, GR activity,
      mitochondrial membrane potential, and Bcl-2 protein expression were all
      increased, while apoptosis, ROS production, cytoplasmic Ca2+ levels, caspase-3
      activity, and Bax, Grp78 and CHOP expression were all significantly reduced in
      the MnTMPyP group compared to PQ group. CONCLUSION: MnTMPyP effectively reduced
      PQ-induced lung epithelial-like cell injury, and the underlying mechanism is
      related to antagonism of PQ-induced oxidative stress.

PMID- 30185697
TI  - Toward the harmonization of work with treatment and prevention for patients with
      chronic respiratory failure.
AB  - Home oxygen therapy (HOT), also known as long-term oxygen therapy, is prescribed
      to patients with chronic respiratory failure (CRF) due to advanced respiratory
      diseases, as it has been shown to improve the prognosis of patients with chronic
      obstructive pulmonary disease (COPD). However, the therapeutic impact of HOT does
      not fully reflect the "socialization" of patients, which is one of the final
      goals of "comprehensive pulmonary rehabilitation", proposed by the Japanese
      Respiratory Society. Since working is one form of socialization, we evaluated a
      55-year-old worker prescribed with HOT for the management of advanced COPD to
      elucidate and assess the social barriers experienced by HOT users. This case
      demonstrates a variety of factors affecting patients, respiratory physicians,
      occupational physicians, and management teams, which prevents patients from
      working. By elucidating these factors and seeking solutions, the promotion of the
      "harmonization of work with treatment and prevention" will both improve working
      environments and encourage CRF patients to continue working, leading to better
      socialization. Thus, the "harmonization of working with treatment and prevention"
      for CRF patients is a core goal for the promotion of both "health and
      productivity management" and "comprehensive pulmonary rehabilitation."

PMID- 30185699
TI  - [Occurrence of acquired factor V inhibitor during antibiotic therapy for a
      surgical wound infection].
AB  - Acquired factor V (FV) inhibitor is a rare disorder. Herein we report a case of
      an 82-year-old Japanese woman with FV inhibitor exhibiting a pseudo decline in
      the activities of the multiple coagulation factors. After rectal cancer surgery,
      she received antibiotic therapy for wound infection. As prothrombin and activated
      partial thromboplastin time was prolonged, heparin for atrial fibrillation was
      discontinued without improvement. Coagulation factor activity assays revealed
      deficiencies in II, V, VII, VIII, IX, X, XI, and XII factor activities; in
      particular, the FV activity was markedly decreased to <1%. The cross-mixing test
      findings revealed an inhibitor pattern, and multiple coagulation factor
      inhibitors were positive. The FV inhibitor level was high at 62 Bethesda U/ml.
      The patient exhibited no bleeding tendency with the prolonged wound infection
      without immunosuppressive therapy. The inhibitor disappeared four months after
      the onset.

PMID- 30185698
TI  - [Successful treatment with brentuximab vedotin maintenance therapy after
      autologous stem cell transplantation in high-risk Hodgkin lymphoma].
AB  - A 56-year-old woman was diagnosed with classical Hodgkin lymphoma in December
      2012. She achieved complete remission (CR) with six cycles of adriamycin,
      bleomycin, vinblastine, and dacarbazine (ABVD). In March 2015, she experienced a
      relapse marked by high fever, respiratory discomfort, and pain in the left thigh
      owing to tumor involvement of the femur. She was treated with one cycle of
      brentuximab vedotin (BV), followed by irradiation of the left femoral lesion. She
      achieved partial remission (PR) but developed recurrence after the third cycle of
      BV. She achieved PR again with two cycles of standard bleomycin, etoposide,
      doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone
      (BEACOPP) regimen; therefore, autologous stem cell transplantation (ASCT) was
      performed. Because the dosing interval used for BV therapy was longer than that
      in the recommended schedule, we could not definitively attribute her recurrence
      to BV resistance. Moreover, she maintained a good performance status after
      recurrence during subsequent cycles of BV therapy. Because of attaining PR after
      ASCT, she subsequently received a total of 12 BV cycles for consolidation. She
      achieved CR 3 months after ASCT and has remained in CR until 29 months. For
      patients who show relapse after initial BV therapy, retreatment with BV should be
      carefully considered. Patients who show relapse after achieving at least PR with
      initial BV therapy are potential candidates for post-ASCT BV maintenance therapy
      to reduce their tumor burden.

PMID- 30185701
TI  - [Significance of HLA 1-locus mismatch and ATG administration in unrelated
      hematopoietic stem cell transplantation].
AB  - HLA 1-locus-mismatched unrelated donors (1MMUD) are used in allogeneic
      hematopoietic stem cell transplantation (allo-HCT) for patients who lack an HLA
      matched donor. Here we retrospectively reviewed 3,313 patients with acute
      leukemia or myelodysplastic syndrome who underwent bone marrow transplantation
      from an HLA allele-matched unrelated donor (MUD) or 1MMUD in 2009-2014. We
      compared the outcomes of MUD (n=2,089) and 1MMUD with antithymocyte globulin
      [ATG; 1MM-ATG (+) ; n=109] with those of 1MMUD without ATG [1MM-ATG (-) ;
      n=1,115]. In the 1MM-ATG (+) group, the median total dose of ATG (thymoglobulin)
      was 2.5 (range, 1.0-11.0) mg/kg. The rates of grade III-IV acute GvHD, non
      relapse mortality (NRM), and overall mortality were significantly lower in the
      MUD group than in the 1MM-ATG (-) group [hazard ratio (HR) 0.77; P=0.016; HR,
      0.74, P<0.001; and HR, 0.87, P=0.020, respectively]. Similarly, the rates of
      grade III-IV acute GvHD, NRM, and overall mortality were significantly lower in
      the 1MM-ATG (+) group than in the 1MM-ATG (-) group (HR, 0.42, P=0.035; HR, 0.35,
      P<0.001; and HR, 0.71, P=0.042, respectively). Even in the recent cohort, the
      outcome of allo-HCT from 1MM-ATG (-) was inferior to that of allo-HCT from MUD.
      Nevertheless, the negative impact of 1MMUD disappeared with the use of low-dose
      ATG without exacerbating the risk of relapse.

PMID- 30185700
TI  - [Airway obstruction due to localized tracheal lesion of extranodal NK/T-cell
      lymphoma, nasal type].
AB  - A 76-year-old man presented with a tracheal tumor associated with severe
      respiratory obstruction. A tracheotomy was performed due to respiratory failure.
      F-fluorodeoxyglucose (FDG) -positron emission tomography/computed tomography
      revealed an abnormal accumulation of FDG (maximum standardized uptake value: 16)
      in the trachea. A histopathological examination of the tracheal biopsy revealed
      extranodal NK/T-cell lymphoma, nasal type (ENKL). He was treated with concurrent
      radiotherapy (50 Gy) for the tracheal tumor and three courses of two-thirds dose
      ofdexamethasone, etoposide, ifosfamide, and carboplatin. Although the tumor
      responded remarkably well to this therapy, the patient died of an ENKL recurrence
      in the lungs and liver 11 months post therapy.

PMID- 30185702
TI  - [Thrombosis in multiple myeloma].
AB  - Reportedly, patients with cancer have an increased risk (four- to seven-fold) of
      developing thrombotic events (TEs) compared with healthy volunteers. Multiple
      myeloma (MM) is one of the neoplasms that exhibit a high incidence of TEs, and
      approximately 10% patients with MM develop TEs during their clinical courses. The
      underlying risk factors of TEs are classified into patient-, disease-, and
      treatment-related factors. Specific treatment-related risk factors comprise the
      use of immunomodulatory drugs combined with dexamethasone. As the occurrence of
      TE in patients hampers the treatment for MM itself, which results in unfavorable
      outcomes, elucidating TE pathogenesis and adequate prophylaxis for each patient
      are essential to prevent MM-related TEs.

PMID- 30185703
TI  - [Thrombosis in myeloproliferative neoplasms].
AB  - Among all types of myeloproliferative neoplasms (MPNs), polycythemia vera (PV)
      and essential thrombocythemia (ET) require careful management of both thrombosis
      and hemostasis. One recent concern associated with MPNs is the JAK2 mutation
      (V617F). This mutation is essential for MPN pathology, but it has also garnered
      attention for its association with thrombosis. Several studies have reported the
      mechanisms underlying the onset of thrombosis in both PV and ET and have also
      discussed the association between JAK2 mutations and thrombotic tendencies.
      Arterial thrombosis is a common clinical symptom that is associated with the
      diagnosis and course of both PV and ET. Particularly, cerebral infarction has
      been identified as the leading cause of death in patients with untreated PV.
      Notably, PV and ET are also associated with a high incidence of venous
      thromboembolism (VTE). The occurrence of this type of thrombosis at atypical
      sites, such as cerebral venous sinus thrombosis and splanchnic vein thrombosis
      (SVT), is not uncommon. Generally, patients with PV and ET have good life
      expectancy; their treatment essentially focuses on dealing with thrombosis and
      bleeding. Phlebotomy may be used for treating patients with PV; however, low-dose
      aspirin is used to prevent the onset of arterial thrombosis. For patients with a
      history of VTE, oral anticoagulants are commonly prescribed to prevent
      recurrence.

PMID- 30185704
TI  - [Paroxysmal nocturnal hemoglobinuria and thrombosis in the era of eculizumab].
AB  - Paroxysmal nocturnal hemoglobinuria (PNH) arises as a consequence of clonal
      expansion of hematopoietic stem cells that have acquired a somatic mutation in
      the PIGA gene. The resulting hematopoietic cells have deficiencies in the GPI
      anchored complement regulatory proteins CD55 and CD59, which account for the
      intravascular hemolysis that is the primary clinical manifestation of PNH.
      Thromboembolism is a major cause of morbidity and mortality in PNH, particularly
      in Caucasian patients. In a previous report on the clinical course of PNH
      patients in the United States and Japan, we showed that thrombosis was
      significantly more prevalent in white PNH patients than in Asian PNH patients.
      The pathophysiological mechanisms underlying thrombosis in PNH have not been
      fully clarified, and multiple factors are likely to be involved. Eculizumab, a
      humanized monoclonal antibody, targets the terminal complement protein C5 and
      inhibits terminal complement-mediated hemolysis associated with PNH. Brodsky et
      al. reported that eculizumab treatment reduces the risk of clinical
      thromboembolism in patients with PNH. These facts strongly suggest that the main
      cause of thrombosis in PNH is complement activation and/or hemolysis. In this
      review, the pathophysiology of thrombosis in PNH is discussed in the context of
      observations in PNH patients treated with eculizumab.

PMID- 30185705
TI  - [Involvement of innate immunity in the expansion of multiple myeloma cells and
      therapeutic intervention with lenalidomide].
AB  - Multiple myeloma (MM) cells acquire dormancy and drug resistance via their
      interaction with bone marrow stroma cells (BMSCs) in a hypoxic microenvironment.
      In this study, we found a positive expression of CD180/MD-1 complex (a non
      canonical toll-like receptor) on MM cells, which was markedly up-regulated under
      adherent and/or hypoxic conditions. Bacterial lipopolysaccharide (LPS) enhanced
      the growth of MM cells via the activation of MAP kinases, an effect which showed
      a positive correlation with the expression levels of CD180. LPS administration
      significantly increased CD180/CD138 double-positive cell number in a murine
      xenograft model after the inoculation of MM cells directly attached to BMSCs.
      Notably, the shRNA-mediated knockdown of CD180 terminated the LPS response in
      vitro and in vivo. Promoter analyses identified IKZF1 (Ikaros) as a pivotal
      transcriptional activator of the CD180 gene, whose transcription was activated
      via cell adhesion and hypoxia by increasing Ikaros expression and its binding to
      the promoter region. Pharmacological targeting of Ikaros with lenalidomide
      ameliorated the response of MM cells to LPS in a CD180-dependent manner in vitro
      and in vivo. CD180/MD-1 pathway may represent a novel mechanism for the
      regulation of the growth of MM cells in BM milieu and may serve as a therapeutic
      target to prevent the regrowth of dormant MM cells.

PMID- 30185706
TI  - [Clinical development of CAR-T therapy for refractory multiple myeloma].
AB  - A chimeric antigen receptor (CAR) comprises an extracellular ligand recognition
      domain linked to CD3zeta and induces T-cell activation upon antigen binding.
      Recently, the potential of CD19-targeted CAR T-cells (CAR-T) to treat multiple
      myeloma has been explored. A group in the University of Pennsylvania reported
      that 4 out of 10 patients with refractory myeloma achieved an objective response
      (sCR: 1, VGPR: 1, and PR: 2). Although the resultant cancer ablation was an
      arresting sight, it remains unclear whether CD19 is a suitable target for
      myeloma. Therefore, CAR-T therapy employing alternative target antigens is being
      attempted. Some current clinical trials are utilizing CAR against differentiation
      antigens, including CD138, CD38, and kappa light chain. B-cell maturation antigen
      (BCMA) is also a potential candidate. A group in the NCI described 12 patients
      with refractory myeloma enrolled in a BCMA-CAR phase 1 clinical trial. Two
      patients receiving the highest dosage attained an objective response.
      Nevertheless, considerable research is required for CAR immunotherapy to become
      universally available to patients with myeloma. The current enthusiasm for the
      development of this cutting-edge technology is justified because extraordinary
      evidence indicates that it is effective, although this may not apply to every
      case. CAR-T therapy for myeloma is currently undergoing rapid, wide-scale growth
      both in academia and in industry-sponsored clinical development.

PMID- 30185708
TI  - [Development of myeloproliferative neoplasms by mutant calreticulin: underlying
      mechanisms].
AB  - Unique frameshift mutations in the calreticulin (CALR) gene, which encodes a
      molecular chaperone present in the endoplasmic reticulum, were identified in a
      subset of patients with myeloproliferative neoplasms (MPNs). Recently, it has
      been reported that mutant CALR constitutively activates the thrombopoietin (TPO)
      receptor MPL, even in the absence of TPO, thereby inducing cellular
      transformation. Hence, the tumorigenic role of mutant CALR in the development of
      MPNs is now clear; nevertheless, the precise molecular mechanism the interaction
      between mutant CALR and MPL remains elusive. We recently illustrated that the
      accumulation of mutant CALR in the Golgi apparatus and its N-glycan binding
      capacity are needed for its tumorigenic capacity, including the interaction and
      activation of MPL. These findings implied that mutant CALR recognizes MPL during
      the receptor maturation using its original property as a molecular chaperone.
      Although the molecular mechanism underlying the activation of MPL by CALR remains
      elusive, it became clear that the mechanism of interaction between mutant CALR
      and MPL is quite different from that of TPO, the natural ligand, and MPL.

PMID- 30185707
TI  - [Myeloproliferative neoplasms: revisions in the 2016 WHO criteria].
AB  - The 2016 revised WHO classification of tumors of hematopoietic and lymphoid
      tissues has incorporated novel molecular markers, such as calreticulin (CALR)
      mutations, for the diagnosis of myeloproliferative neoplasms (MPNs). Typically,
      CALR mutations are detected in 25%-30% of patients with essential thrombocythemia
      (ET) or primary myelofibrosis (PMF) and can lead to frameshifts that produce
      proteins with a novel C-terminal. In addition, the CALR mutation plays a crucial
      role in the MPN pathogenesis. The second major revision comprises the change in
      RBC parameters for polycythemia diagnosis; additionally, it emphasizes BM biopsy
      for the diagnosis of PV. Previously, PV was often underdiagnosed when considering
      the Hb levels of >18.5 g/dl for males and >16.5 g/dl for females; thus, the 2016
      revision lowered these levels to >16.5 g/dl for males and >16.0 g/l for females.
      The third major revision is the introduction of a novel entity
      "prefibrotic/early" PMF (prePMF) to PMF. Although megakaryocytic proliferation
      and atypia were observed in in BM biopsy specimens of prePMF, these were not
      accompanied by reticulin fibrosis > grade 1. Thus, the inferior prognosis of
      prePMF was reported in comparison with "true" ET.

PMID- 30185709
TI  - [Significance of somatic mutations on the prognosis of myelodysplastic
      syndromes].
AB  - During the past decade, substantial advances have been made in our understanding
      of the genetic basis of myelodysplastic syndromes (MDS), wherein a spectrum of
      major mutational targets associated with MDS, such as splicing factors and
      epigenetic regulators, has been revealed. The impact of mutations in these genes
      on disease subtypes and prognosis has also been evaluated. A mutation in SF3B1,
      one of the spliceosome machinery components, defines a distinct MDS subtype
      characterized by ring sideroblasts, indolent clinical course, and favorable
      clinical outcome. On the other hand, mutation in TP53 is observed in 5-10% of
      cases and is associated with an aggressive phenotype, higher frequency of copy
      number abnormalities, and poor prognosis. Even in the setting of hematopoietic
      stem-cell transplantation, patients with TP53 mutations, particularly in cases
      where complex cytogenetic abnormalities were also present, showed extremely poor
      prognosis. Because the importance of molecular profiles in the prognosis of MDS
      is being better understood, treatment decisions may begin incorporating this
      information in addition to conventional clinical factors.

PMID- 30185711
TI  - [Impact of peri-SCT immune modulation on Treg homeostasis and GVHD].
AB  - Post allogeneic hematopoietic stem cell transplantation, CD4+CD25+Foxp3+
      regulatory T cells (Tregs) play a central role in the maintenance of self
      tolerance and immune homeostasis. In recent years, various immune-modulating
      agents, including cyclophosphamide, mogamulizumab, and antibodies to inhibitory
      co-stimulating molecules (CTLA-4 and PD-1), have been used to control donor
      derived immunity or host-tumor burden during the peritransplant period; however,
      the underlying impact of these agents on Treg homeostasis is yet to be
      characterized. In particular, recent retrospective analyses suggested that
      blockade (an inhibitory molecule) before and after HSCT was associated with
      abnormal Treg homeostasis and the development of severe acute GVHD and other
      immune-mediated complications. Our recent studies, using murine model and
      clinical sample analyses, aim to define the effects of immune-modulating agents
      on the reconstitution of each lymphocyte subset, particularly in terms of Treg
      homeostasis. An enhanced understanding of the reconstituting mechanisms and the
      target-specificity of post-HSCT GVL response combined with novel immunotherapy
      will enable the development of a safe and efficient therapeutic strategy.

PMID- 30185710
TI  - [Impact of mismatched HLA on graft-versus-host disease in unrelated stem cell
      transplantation].
AB  - Graft-versus-host disease (GVHD) caused by patient and donor human leukocyte
      antigen (HLA) mismatch is a complication of unrelated hematopoietic stem cell
      transplantation (UR-HSCT) that leads to reduced success rates. To date, studies
      on HLA alleles in transplant have provided important information on unrelated
      donor selection. In this study on the effects of specific HLA alleles on acute
      GVHD in UR-HSCT, HLA-C*14:02 was found to be significantly associated with an
      increased risk of acute GVHD. Patient HLA-C*14:02 and donor HLA-C*15:02 mismatch
      was usually KIR2DL-ligand mismatch in the GVH direction in Japanese UR-HSCT
      cohort, and the higher risk of severe acute GVHD for KIR2DL-ligand mismatch in
      GVH direction demonstrated in previous Japanese UR-HSCT study was attributable to
      this particular mismatch combination. Recently, the risk of acute GVHD after UR
      HSCT was reported to be associated with the HLA-DP expression level, which is
      associated with the variant rs9277534 located in the 3'untranslated region (UTR)
      of the HLA-DPB1 gene. We constructed phylogenetic trees of HLA-DPB1 alleles using
      next-generation sequencing (NGS) HLA typing data that included introns and
      3'UTRs. Results reported that rs9277534 represented a highly conserved region
      from exon 3 to the 3'UTR, which may lead to acute GVHD via a mechanism different
      from that observed using T-cell epitope mismatching algorithms, perhaps
      reflecting exon 2 polymorphisms. The usage of innovative technologies such as NGS
      in genetic analysis and HLA typing thus has profound implications in this field.

PMID- 30185713
TI  - ?

PMID- 30185712
TI  - [Graft-versus-host disease-free, and relapse-free survival in Japanese patients
      with hematological malignancies].
AB  - Graft-versus-host disease (GVHD) -free, relapse-free survival (GRFS) is an
      important, composite endpoint for clinical trials, which provides a patient
      centered measure of transplant success. This review discusses the results of the
      Japanese Transplant Registry study. This large-scale study examined 23,302
      patients with hematological malignancy and characterized GRFS according to a
      variety of graft sources. The GRFS rate at 1 year was 41% in all patients. GRFS
      was superior in patients undergoing bone marrow transplantation compared to
      peripheral blood stem cell transplantation, owing to lower risk of developing
      grades III-IV acute and chronic GVHD. The best GRFS rates were observed in
      patients that received HLA-matched related bone marrow transplants; however, this
      was not the case in HLA-mismatched donors. GRFS after single-cord blood
      transplantation was almost comparable with HLA-matched unrelated bone marrow
      transplantation, possibly due to the low risk of chronic GVHD. Other factors
      associated with increased GRFS rates included female patients; use of anti
      thymocyte globulin prophylaxis for standard-risk disease; recent
      transplantations; gender combinations other than from a female donor to a male
      patient; absence of prior autologous transplantation; myeloablative conditioning;
      negative cytomegalovirus serostatus; and use of tacrolimus-based GVHD
      prophylaxis. These results provide valuable information for deciding the best
      choice of graft sources and type of GVHD prophylaxis to be used.

PMID- 30185714
TI  - ?

PMID- 30185715
TI  - ?

PMID- 30185716
TI  - [Clinical significance of chronologic immature platelet fraction analysis in
      TAFRO syndrome].
AB  - TAFRO syndrome is characterized by thrombocytopenia with unknown etiology. The
      assessment of immature platelet fraction (IPF) is useful for differential
      diagnoses that include thrombocytopenia. However, the significance of IPF in
      cases of TAFRO syndrome remains to be reported. We present a case of TAFRO
      syndrome wherein the patient demonstrated a marked increase in IPF without
      thrombocytopenia, which offers vital information concerning TAFRO diagnosis and
      the serial measurements of IPF during treatment. A 65-year-old man presenting
      with fever was admitted to our hospital. He exhibited mild splenomegaly and
      lymphadenopathy, as well as rapidly worsening renal failure and fluid retention.
      These indications prompted the initiation of corticosteroid therapy. A normal
      platelet count and aberrantly high IPF implied abnormal thrombopoiesis, and
      subsequent bone-marrow findings suggested TAFRO syndrome. The platelet counts
      started to decrease following the corticosteroid therapy, but the treatment
      refractoriness prompted the urgent administration of rituximab. Thereafter, the
      platelet count nadir remained for approximately one month, whereas the decreasing
      IPF trend preceded platelet recovery. In the present case, a high pre-treatment
      IPF was demonstrated before the emergence of thrombocytopenia, and a decreasing
      trend of IPF was observed before platelet recovery during treatment. Therefore,
      serial IPF measurements could be useful for the early diagnosis and
      prognostication of TAFRO syndrome.

PMID- 30185717
TI  - [Evans syndrome complicated with multicentric Castleman disease successfully
      treated with tocilizumab].
AB  - A 26-year-old man presented with fever, multiple lymphadenopathies, polyclonal
      hypergammaglobulinemia, and an elevated serum interleukin-6 (IL-6) level.
      Multicentric Castleman disease (MCD) was diagnosed by lymph node biopsy.
      Treatment with prednisolone (PSL) was initiated; however, its efficacy was
      limited. During PSL tapering, rapidly progressive anemia and thrombocytopenia
      developed concurrently with increased reticulocyte level, elevated serum LDH
      level, decreased haptoglobin level, and positive direct Coombs test. Based on
      these findings, Evans syndrome, which is a concurrent development of autoimmune
      hemolytic anemia and immune thrombocytopenia, was confirmed. The PSL dose was
      increased but was ineffective. Therefore, treatment with tocilizumab was
      initiated, and the clinical findings of both MCD and Evans syndrome improved. The
      clinical course of this case suggests that tocilizumab could be a treatment
      option for Evans syndrome complicated with MCD. Three other cases of Evans
      syndrome complicated with MCD have also been reported; however, this is the first
      case that shows the efficacy of tocilizumab as treatment for both MCD and Evans
      syndrome.

PMID- 30185718
TI  - Visceral adipose tissue increases shortly after the cessation of GH therapy in
      adults with Prader-Willi syndrome.
AB  - GH therapy in pediatric patients with Prader-Willi syndrome (PWS) improves body
      composition, but discontinuation of GH after achieving adult height has been
      implicated in its deterioration. Although there is evidence for the deleterious
      effects of visceral adipose tissue (VAT) rather than subcutaneous adipose tissue
      (SAT) on the development of obesity-related complications, the effects of GH
      discontinuation on fat distribution in adults with PWS has not been fully
      investigated. Therefore, we utilized dual-energy X-ray absorptiometry (DEXA) and
      abdominal computed tomography (CT) to compare the fat distribution between before
      and 6 months or 12 months after the cessation of GH therapy in 7 adult PWS
      patients. GH therapy was initiated at a mean age of 4.1 +/- 1.4 years and
      discontinued at a mean age of 18.9 +/- 1.8 years. Serum IGF-1 levels were
      decreased by discontinuation of GH therapy. Fat mass was significantly increased
      6 and 12 months after GH cessation, whereas muscle mass and bone mineral density
      were unchanged during both study periods. Abdominal CT analysis revealed that
      elevations in fat mass were due to increases in VAT rather than SAT. Circulating
      low-density lipoprotein (LDL) cholesterol levels were significantly elevated 6
      months after GH cessation. In conclusion, discontinuation of GH therapy caused
      rapid increases in visceral adipose tissue and LDL cholesterol levels. These
      findings indicate that continuation of GH therapy may be a therapeutic option to
      maintain body composition; however, further studies regarding the long-term
      benefits and adverse effects of GH therapy in adults with PWS are required.

PMID- 30185719
TI  - Pharmacokinetics of insulin disappearance after massive overdosing.
AB  - Long-term glucose supplementation is required to prevent hypoglycemia after
      massive insulin overdosing. We fitted the blood insulin concentration-time
      profile to the model: I = A.exp(-a.t) + B.exp(-b.t), where I (MUU/mL) is the
      serum/plasma insulin concentration, A (MUU/mL) and B (MUU/mL) are the peak
      insulin concentrations of each component, a (time-1) and b (time-1) are the time
      constants of each component, and t (h) is the time elapsed from the peak of blood
      insulin level. Additional components were considered as needed. Patient 1 had
      auto-injected 600 U NovoRapid(r) 30Mix, and Patient 2 had auto-injected 300 U
      Novolet(r)R (regular) and 1,800 U NovoLet(r)N (NPH). We used the disappearance of
      therapeutic doses of the respective insulin in healthy individuals as controls,
      and we obtained parameters by Excel solver. In Patient 1, the parameter values
      were A = 1490.04 and a = 0.15 for insulin aspart and B = 60.66 and b = 0.04 for
      protaminated aspart. In Patient 2, the values were A = 784.45 and a = 0.38 for
      regular insulin and B = 395.84 and b = 0.03 for NPH. Compared with controls, the
      half-lives (t1/2) for insulin aspart and protaminated aspart were 4 and 2 times
      longer, respectively, in Patient 1. In Patient 2, the t1/2 for regular and NPH
      insulin were 2 and 7 times longer than those in the controls, respectively. In
      conclusion, the t1/2 for insulin was elongated 2 to 7 times after massive
      overdosing, explaining why glucose supplementation is needed for long periods in
      these cases.

PMID- 30185720
TI  - DSH5, a dihydrosphingosine C4 hydroxylase gene family member, shows spatially
      restricted expression in rice and is lethal when expressed ectopically.
AB  - Dihydrosphingosine C4 hydroxylase (DSH), a diiron-binding membrane enzyme,
      catalyzes the hydration of dihydrosphingosine and acyl-sphinganine to produce
      phytosphingosine and phytoceramide, respectively. Rice has two types of DSH
      homologs: general DSHs, namely DSH1, DSH2 and DSH4, and others that show spatial
      expression profiles, namely DSH3 and DSH5. The general DSHs exist in many plant
      species. These DSHs showed similarity in their functions and complemented the
      yeast sur2D mutation. In contrast, homologs of DSH3 and DSH5 were found only in
      monocot plants. Phylogenetic analysis placed these DSHs in different clades that
      are evolutionarily divergent from those of the general DSHs. DSH3 and DSH5 showed
      low-level expression. DSH5 expression was specifically in vascular bundle
      tissues. Ectopic expression of DSH5 induced a dwarf phenotype characterized by
      severe growth inhibition and an increase in the thickness of the leaf body caused
      by enlargement of bulliform cells in the leaves. However, no significant
      difference was observed in the amount of sphingolipid species. DSH5 did not
      complement the yeast sur2D mutation, implying that DSH5 has little effect on
      sphingolipid metabolism. These findings suggested that DSH3 and DSH5 originated
      and diverged in monocot plants.

PMID- 30185721
TI  - Anaplastic oligodendroglioma with leptomeningeal dissemination in a french
      bulldog.
AB  - A 2.5-year-old male French Bulldog was evaluated for seizures. Cranial magnetic
      resonance imaging (MRI) suggested a glioma in the left piriform area. Radiation
      therapy (RT) and continuous chemotherapy were administered. Although the lesion
      had regressed significantly 2 months after RT, a follow-up MRI revealed meningeal
      enhancement in the left piriform area, which expanded further, with
      hydrocephalus, by day 310 (8 months after RT). Because of the poor prognosis, the
      dog was euthanized on day 356 and necropsy was performed. Histopathological
      examination confirmed anaplastic oligodendroglioma with leptomeningeal
      dissemination. This case suggests that the possibility of leptomeningeal
      dissemination and hydrocephalus should be considered even after RT and
      chemotherapy for anaplastic oligodendroglioma.

PMID- 30185722
TI  - Candida parapsilosis and Candida tropicalis infections in an Okhotsk snailfish
      (Liparis ochotensis).
AB  - An Okhotsk snailfish (Liparis ochotensis) kept at Nagoya aquarium exhibited
      sudden death. Microscopically, the fish showed multiple granulomatous foci in the
      gills, liver and kidney. Multiple yeast-like organisms as well as pseudohyphal
      elements were observed within granulomatous lesions. Immunohistochemically, the
      hyphae were negative for both Asperigullus and Mucor spp., and a weak positive
      for Candida sp. The seminated-PCR product was consistent with Candida
      parapsilosis and C. tropicalis. This is the first record of disseminated mycotic
      granulomatous lesion due to C. parapsilosis and C. tropicalis infection in fish.

PMID- 30185723
TI  - Population structure of the raccoon dog (Nyctereutes procyonoides) using
      microsatellite loci analysis in South Korea: Implications for disease management.
AB  - The prevention and control of infectious diseases transmitted by wildlife are
      gaining importance. To establish effective management strategies, it is essential
      to understand the population structure of animals. Raccoon dogs (Nyctereutes
      procyonoides) in South Korea play a key role in the maintenance of food web
      stability and possess genetic compositions that are unique compared to those in
      other areas. However, wild raccoon dogs play another role as the main host of
      various infectious diseases. To establish long-term strategies for disease
      management, we investigated the genetic structure and possible geographic
      barriers that influence the raccoon dog population in South Korea by analyzing 16
      microsatellite loci. The present study showed that mountains were the major
      factors responsible for genetic structuring, along with distance. We proposed
      potential management units (MUs) for raccoon dogs based on the genetic
      structuring and gene-flow barrier data obtained in this study. Four MUs were
      suggested for the Korean raccoon dog population (Northern, Central, Southwestern,
      and Southeastern). The Korean raccoon dog population structure determined in this
      study and the proposed MUs will be helpful to establish pragmatic strategies for
      managing Korean raccoon dog population and for preventing the transmission of
      infectious diseases.

PMID- 30185724
TI  - Detection of serum antibodies to Brucella in Russian aquatic mammals.
AB  - A serologic survey of Brucella infection was performed in Caspian seals (Pusa
      caspica, n=71), Baikal seals (P. sibirica, n=7), ringed seals (P. hispida
      hispida, n=6), and beluga whales (Delphinapterus leucas, n=4) inhabiting Russian
      waters, by enzyme-linked immunosorbent assay (ELISA) using Brucella abortus and
      B. canis as antigens. The sera of 4 Caspian seals (4%) tested positive for B.
      abortus. The same sera samples demonstrated weaker yet detectable affinity for B.
      canis antigens. Several discrete bands against B. abortus and B. canis antigens
      were detected on Western blot analysis of the ELISA-positive seal sera; the bands
      against B. canis were weaker than those against B. abortus. The sera of 3 beluga
      whales (75%) were positive for B. abortus antigens but showed no binding to B.
      canis antigens in the ELISA. The positive whale sera showed a strong band
      appearance only against B. abortus antigens in the Western blot analysis. Many
      detected bands were discrete, while some of them had a smeared appearance. The
      present results indicate that Brucella infection occurred in Caspian seals and
      beluga whales inhabiting Russian waters, and that the Brucella strains infecting
      the seals and the whales were antigenetically distinct.

PMID- 30185725
TI  - Uterine metastatic rhabdomyosarcoma in a scimitar-horned oryx (Oryx dammah).
AB  - A 13-year-old female scimitar-horned oryx (Oryx dammah) died after progressive
      anorexia, weight loss, and depression. The necropsy showed that the
      retroperitoneum was compressed by a large white-to-tan uterine mass and on
      several sections of the mass, the uterine wall was markedly thickened because of
      ill-defined transmural tumor tissue. Metastatic nodules were detected in the
      omentum, mesentery, diaphragm, and lung. The genital tract and pulmonary and
      abdominal nodules exhibited highly pleomorphic sarcoma. The primary and
      metastatic neoplastic cells showed positive results for vimentin, desmin, and
      sarcomeric actin, and negative results for smooth muscle actin. Uterine
      metastatic rhabdomyosarcoma was diagnosed on the basis of the gross,
      histopathology and immunohistochemistry results.

PMID- 30185727
TI  - [Pharmacological characteristics and clinical efficacies of a novel potassium
      competitive acid blocker, vonoprazan fumarate].
AB  - Proton pump inhibitors (PPIs) inhibit H+, K+-ATPase, an enzyme which is the final
      step of gastric acid secretion and is selectively located in the gastric parietal
      cells. PPIs block the enzyme in a covalent and irreversible binding manner, thus
      providing better efficacy than previous pharmacological agents such as antacids
      and histamine H2 receptor antagonists. Although PPIs have been the first-line
      therapeutic option for acid related diseases (ARDs), there are several
      limitations to their efficacy, i.e. short half-life in blood, insufficient acid
      suppression especially at night, necessity of repeated dosages for full action,
      and large variation in efficacy among patients due to CYP2C19 polymorphism. To
      overcome these shortcomings, we performed a high-throughput random screening
      using in-house chemical libraries and further lead optimization to look for the
      most relevant clinical candidate compounds. As the results of these researches,
      we discovered vonoprazan fumarate, a novel gastric acid antisecretory agent which
      inhibits H+, K+-ATPase in a reversible and K+-competitive manner. Vonoprazan
      exerted a more potent and longer lasting inhibitory effect than lansoprazole on
      gastric acid secretion in preclinical studies, presumably by its high
      accumulation profile in the gastric parietal cells. It also exhibited a rapid
      onset of action and prolonged inhibition of intragastric acidity in humans and
      showed remarkable effects on multiple ARDs including erosive esophagitis and
      Helicobacter pylori eradication. Vonoprazan fumarate was approved in 2014 for
      clinical use in Japan. Vonoprazan is a new therapeutic option which can
      potentially improve outcomes compared with conventional PPI-based treatments for
      ARDs.

PMID- 30185729
TI  - [The role of pharmacology to produce firuglipel (DS-8500a), an orally available
      GPR119 agonist for type 2 diabetes mellitus].
AB  - GPR119 (G-protein coupled receptor 119) has been shown to be highly expressed in
      the lower small intestinal and colorectal L-cells and pancreatic beta-cells, and
      mediates intracellular cAMP concentration, glucagon like peptide (GLP-1)
      secretion, and glucose stimulated insulin secretion (GSIS). As the next
      generation for the treatment of type 2 diabetes mellitus (T2DM), GPR119 agonist
      has been intensively studied by pharmaceutical companies and a lot of patents
      have been applied by them. In such highly competitive condition, biological
      differentiation and to find an advantage among GPR119 agonists were necessary to
      proceed the candidate compound in further clinical investigation. Firuglipel (DS
      8500a) is an orally available GPR119 agonist synthesized in DAIICHI SANKYO CO.,
      LTD (DS). It was originated from DS-chemical library and optimized in the aspect
      of bioavailability and safety. Firuglipel had a higher intrinsic activity (IA) of
      the production of intracellular cAMP in human GPR119 expressing CHO-K1 cells than
      those of other GPR119 agonists studied. The level of IA in each GPR119 agonist
      was correlated with the existence of agonist conformer. In parallel with the
      study for the differentiation from other GPR119 agonists, we compared firuglipel
      with dipeptidyl peptide-4 (DPP-4) inhibitor in NONcNZO10/LtJ mice and evaluated
      their combination in streptozotocin (STZ) treated C57BL/6J mice to clarify future
      positioning among anti-diabetics therapy. These pharmacological studies
      illustrated here can draw out a clinical value of compound and expected to lead
      the production of first-in-class agent in pharmaceutical companies.

PMID- 30185728
TI  - [Contribution of pharmacological research to the discovery of a first-in-class
      drug, mirabegron, for the treatment of overactive bladder].
AB  - Overactive bladder (OAB) is defined as urgency, with or without urge
      incontinence, usually with frequency and nocturia. Antimuscarinic drugs are often
      prescribed as a standard care; however, the treatment discontinuation due to the
      adverse events including dry mouth and constipation has been an issue. Taking
      these situations into account, we considered that a novel OAB drug having a
      different mechanism from antimuscarinics fills the unmet medical need. It has
      been known that, during bladder filling, activation of sympathetic nerves results
      in bladder smooth muscle relaxation via the beta-adrenergic receptor (AR)
      stimulation. In 1999, three Japanese groups independently provided evidence for
      the existence of beta3-AR in human bladder smooth muscles and some of these
      groups showed that beta3-AR activation is mainly involved in the relaxation
      induced by beta adrenergic stimulation. Therefore, we conducted pharmacological
      research focusing on beta3-AR as a novel target molecule for the treatment of
      OAB. A selective beta3-AR agonist mirabegron showed the relaxant effect in rat
      bladder smooth muscle and decreased resting intravesical pressure in anesthetized
      rats. Mirabegron also improved storage function in a rat detrusor overactivity
      model. Furthermore, in vitro isometric contraction study using human bladder
      tissues was conducted to predict the clinical efficacy and mirabegron showed the
      relaxant effect in human bladder smooth muscle. In clinical studies with OAB
      patients, mirabegron demonstrated promising efficacy and tolerability. These
      pharmacological evidences contributed to the approval of mirabegron as a first-in
      class drug for OAB treatment in Japan ahead of other countries.

PMID- 30185726
TI  - Development of a Quantitative PCR Assay for Arcobacter spp. and its Application
      to Environmental Water Samples.
AB  - Arcobacter spp. are emerging pathogens associated with gastroenteritis in humans.
      The objective of this study was to develop a highly sensitive and broadly
      reactive quantitative PCR (qPCR) assay for Arcobacter spp. and to apply the
      developed assay to different water sources in the Kathmandu Valley, Nepal.
      Fifteen samples to be analyzed by next-generation sequencing were collected from
      13 shallow dug wells, a deep tube well, and a river in the Kathmandu Valley in
      August 2015. Among the 86 potential pathogenic bacterial genera identified,
      Acinetobacter, Pseudomonas, Flavobacterium, and Arcobacter were detected with
      relatively high abundance in 15, 14, 12, and 8 samples, respectively. A primer
      pair was designed with maximal nucleotide homologies among Arcobacter spp. by
      comparing the sequences of 16S rRNA genes. These primers were highly specific to
      most of the known species of Arcobacter and quantified between 1.0*101 and
      6.4*106 copies reaction-1 and sometimes detected as few as 3 copies reaction-1.
      The qPCR assay was used to quantify Arcobacter spp. in bacterial DNA in not only
      the above 15 water samples, but also in 33 other samples collected from 15
      shallow dug wells, 6 shallow tube wells, 5 stone spouts, 4 deep tube wells, and 3
      springs. Thirteen (27%) out of 48 samples tested were positive for Arcobacter
      spp., with concentrations of 5.3-9.1 log copies 100 mL-1. This qPCR assay
      represents a powerful new tool to assess the prevalence of Arcobacter spp. in
      environmental water samples.

PMID- 30185730
TI  - [Muscle mass measurement by DXA and MRI in non-human primates].
AB  - The global population is aging rapidly and, in Japan, the number of elderly has
      been steadily rising. It is important to shrink the gap between the average
      lifespan and the number of years people can expect to remain healthy. This links
      with improving the quality of life for the elderly and reducing social welfare
      spending. Maintaining motor function is believed to be a key to extending the
      number of years a person remains healthy, but recent years have seen a rise in
      locomotive syndrome. Decreases in muscle mass with age, and the deterioration in
      motor functions leads to sarcopenia. However, there is a dearth of medicines for
      increasing muscle mass or muscular strength. In this study, we used non-human
      primates (NHPs), which have similar anatomical features to humans and have
      advanced functional differentiation between the fore- and hindlimbs, to examine a
      highly accurate method of measuring muscle mass using Magnetic Resonance Imaging
      (MRI) and compared it to Dual Energy X-ray Absorptiometry (DXA) usually used in
      clinical settings. The results showed that both MRI and DXA provided high
      repeatability. Furthermore, correlation analysis between the amount of excised
      muscle for measurement and the results from MRI and DXA showed a high correlation
      at all sites examined, with the correlation coefficient higher for MRI than for
      DXA. We expect that the establishment of a highly accurate method for measurement
      of muscle mass using MRI and DXA will give impetus to the development of drugs
      that target muscle mass.

PMID- 30185731
TI  - [Pharmacological profile of a novel nonhuman primate model of knee
      osteoarthritis].
AB  - A number of promising compounds developed in rodent arthritis models lack
      efficacy in clinical osteoarthritis (OA) pain. To enhance successful translation
      of preclinical findings, a nonhuman primate (NHP) model of knee OA was developed
      and characterized using behavioral assessments designed for use in the NHP. A
      unilateral medial meniscectomy (MMx) was performed and animals underwent an
      exercise regimen. Decreased ipsilateral knee pressure threshold, pressure
      "hyperalgesia", and decreased ipsilateral weight bearing, suggestive of pain at
      rest were observed. The sensitivity of the pain-related behaviors to
      pharmacological manipulation was evaluated. A single dose of the opioid morphine
      reduced pain-related behaviors. Likewise, the serotonin-norepinephrine reuptake
      inhibitor duloxetine reduced pain-related behavior, and efficacy was similar to
      that of morphine. By contrast, the anticonvulsant pregabalin did not
      significantly affect pain-related behavior. Repeated dosing with the non
      steroidal anti-inflammatory drug (NSAID) diclofenac reduced pain-related
      behaviors whereas repeated dosing with the NK1 receptor antagonist aprepitant did
      not. The drug effects observed in the NHP OA model mirror the efficacy observed
      clinically.

PMID- 30185732
TI  - [Establishment of retinal disease models using non-human primates and its
      strategy for drug discovery].
AB  - Retinal diseases such as glaucoma, diabetic retinopathy, age-related macular
      degeneration and retinitis pigmentosa are the major causes of blindness. However,
      these pathological mechanisms remain to be elucidated, and development of new
      therapeutic agents has been desired. A large number of experimental animal models
      using rodents (rats and mice) have been used for the evaluations of the
      pathogenesis and novel therapeutic candidates in retinal diseases. However, the
      anatomy of the retina in rodents is different from that in humans, as rodents
      have no macular. Conversely, non-human primates have macular similar to humans,
      and therefore rhesus and cynomolgus monkeys are widely used as experimental
      animal models of retinal diseases. Here, we will introduce non-human primate
      models of retinal diseases and their pharmacological approaches, with a focus on
      our research findings.

PMID- 30185733
TI  - [Pharmacological and clinical profile of spinal muscular atrophy (SMA)
      therapeutic drug nusinersen (Spinraza(r))].
AB  - Nusinersen (Spinraza(r)) was approved as Japan's first antisense oligonucleotide
      (ASO) drug for treatment of SMA (spinal muscular atrophy) patients with a
      deletion or mutation of the survival motor neuron (SMN) 1 gene and >=1 copy of
      the SMN2 gene. Nuseinersen is a fully modified 2'-O-(2-methoxyethyl) (2'-MOE) ASO
      designed to bind the SMN2 pre-mRNA and alter splicing, such that a mature mRNA is
      produced and is translated as full-length SMN protein. In 4 types of mouse SMA
      disease models, treatment with nusinersen improved the form of the neuromuscular
      junction, increased myofiber size, improved righting reflex and grip, and
      prolonged survival. The efficacy of nusinersen was verified in 2 multinational,
      randomized, double-blind, sham-controlled clinical studies in SMA patients with
      differing ages of onset and ages (ENDEAR study and CHERISH study), and
      improvement and maintenance of motor function by nusinersen were demonstrated
      regardless of the type of SMA. Moreover, both studies showed that greater
      efficacy may be obtained with early initiation of nusinersen treatment.
      Therefore, treatment with nusinersen should be started as early as possible to
      delay or halt progression of the disease and maximize therapeutic effect. As
      nusinersen is the only ASO currently available for SMA, it will be widely used,
      therefore we will expect that nusinersen will contribute to improve patients' QOL
      and reduce the burden of caregivers and the healthcare system by improving motor
      function of patients with SMA.

PMID- 30185734
TI  - [The roles of mast cells in tumor microenvironment].

PMID- 30185735
TI  - Extracellular DNA enhances the formation and stability of symplasmata in Pantoea
      agglomerans YS19.
AB  - Extracellular DNA (eDNA) is an important polymeric substance that plays essential
      roles in cell aggregation and nutrient provision for the sessile bacteria. eDNA
      in bacterial biofilms was extensively studied. Here we found that eDNA also
      exists in symplasmata, a bacterial cell aggregate, which is different to a
      biofilm, in the rice enophyte Pantoea agglomerans YS19. We found that exogenous
      eDNA enhanced the formation and stability of symplasmata significantly, and that,
      exogenous eDNA also improved the stress resistance and colonization ability of
      the bacterium on host rice. These results strongly indicate novel roles of the
      eDNA in Pantoea agglomerans YS19, showing its special relation to the stress
      resistance and endophyte-host association of the strain.

PMID- 30185736
TI  - [Experience of Surgical Repair for Cardiac Trauma].
AB  - Cardiac trauma is one of the most lethal injuries. We reported 7 patients with
      cardiac injuries who underwent surgical repair. They were 4 men and 3 women with
      a mean age of 64 years. The mechanisms of injuries were blunt trauma by traffic
      accident in 5 patients and penetrating trauma in 2 patients. The injured cardiac
      chambers were the right atrium in 2, the right ventricle in 2, the right
      ventricle and the ascending aorta in 1,the left atrium in 1 and the left
      ventricle in 1 patient. The wounds of all patients were repaired by direct suture
      closure. Only 1 patient with injuries in the right ventricle and the ascending
      aorta was repaired under cardiopulmonary bypass (CPB). The patient with right
      atrial rupture and concomitant pelvic bone fructure died of retroperitoneal
      hemorrhage. According to the analysis by Trauma and Injury Severity Score(
      TRISS), probability of survival(Ps) values ranged from 0.002 to 0.978. A patient
      with a Ps value of 0.002 died of bleeding. Evaluation of the severity of trauma
      and injury by TRISS was considered generally reasonable.

PMID- 30185737
TI  - [Medium-remote Term Results of the Atrioventricular Valve Replacement with
      Mechanical Valve for Functional Single Ventricles].
AB  - We prospectively investigated the relation of adaptation, timing of
      atrioventricular valve replacement (AVVR), valve type, size, durability of
      replacement valve, and preoperative cardiac function with prognosis of AVVR. The
      subjects included 26 patients[ 15.5 years old( day 2-43 years)] with functional
      single ventricle who underwent AVVR at our institution between August 1996 and
      January 2014. Of these patients, 24 had regurgitation, whereas 2 had stenosis. Of
      7 patients who died, 3 were infants who died in the postoperative acute phase,
      and all of them had severe heart failure at the preoperative stage. The 5-year
      survival rate was 67% as assessed by Kaplan-Meier curve. On univariate analysis
      of the preoperative data, pulmonary artery pressure (PAP), pulmonary capillary
      wedge pressure, age at operation, body height, and body weight were significant
      risk factors for death;of these, only PAP remained in the last model for multiple
      regression analysis. AVVR for regurgitation is supposed to reduce cardiac volume
      load and help improve prognosis. Atrioventricular valve plasty or replacement
      should be performed prior to the development of severe heart failure.

PMID- 30185738
TI  - [Rabbit Model for Evaluation of Anti-adhesive Materials after Open Heart
      Surgery].
AB  - Surgical trauma to the pericardial mesothelium during open heart procedures has
      formation of fibrovascular adhesions. Surgeons are confronted with cardiac
      adhesions, leading to an increased surgical risk such as intractable bleeding and
      possible catastrophic hemorrhage. In order to solve the problem, the anti
      adhesion membrane has been developed and used. However, their performances are
      far from perfect, so it has been expected to develop a novel anti-adhesive
      material. For preparing an anti-adhesive material, there is 1 serious problem, a
      lack of golden standard of animal model for evaluation of anti-adhesivity. In
      this study, we tried to establish a standard system for evaluation of the
      performance of anti-adhesive materials for the chest-area surgery using rabbit.
      Setting the condition of the damage to heart, the objective evaluation system was
      established. And we performed experimental study to evaluate prevention of
      adhesions with pericardial substitutes and our product under development based on
      this model.

PMID- 30185739
TI  - [Surgical Experience of Papillary Fibroelastoma Revealed by Cerebral Infarction].
AB  - Primary cardiac tumors are relatively rare. Among them, papillary fibroelastoma
      (PFE) is the 2nd most common benign cardiac tumor after myxoma. However, despite
      its benign status, PFE may trigger fatal embolic events in some cases. Therefore,
      once PFE is diagnosed, immediate surgical resection of the tumor is recommended.
      We report our experience of 3 patients with cerebral infarction that were
      diagnosed as having PFE. All cases were complicated with cerebral infarction
      probably originating from a tumor embolus or thrombus. For that reason, after the
      tumor had been detected, urgent surgical resection of the tumor was considered to
      be necessary. Given the generally good postoperative outcomes, simple resection
      of the tumor while preserving valve function is considered sufficient to achieve
      a favorable outcome.

PMID- 30185740
TI  - [Right Atrial Approach for the Surgical Repair of Delayed Ventricular Septal
      Rupture].
AB  - Ventricular septal rupture(VSR) after acute myocardial infarction(AMI) is a rare
      and serious complication that is associated with extremely high mortality.
      Delayed VSR is particularly uncommon and is difficult to diagnose and treat. A 68
      year-old man presented with dyspnea on effort. Coronary angiography revealed
      subtotal occlusion of the right coronary artery(RCA) with collateral circulation
      to the chronically and totally occluded left anterior descending artery (LAD).
      Elective stenting of the RCA was successfully performed for a recent MI of the
      RCA, while percutaneous coronary intervention(PCI) in the LAD ended in failure.
      At 21 days after the 1st PCI, the patient developed acute heart failure with new
      pansystolic murmur. Cardiac catheterization showed a left to right ventricular
      shunting without new coronary artery lesions. Fortunately, the hemodynamic status
      was stable, and we could perform elective surgical repair by right atrial
      approach. Simultaneously, a left internal thoracic artery bypass to the LAD was
      performed. The postoperative course was uneventful. The patient is currently
      doing well at 5 years after the operation.

PMID- 30185741
TI  - [Esophageal Achalasia after Surgery for Lung Cancer].
AB  - A 61-year-old man was admitted to our hospital for an abnormal chest shadow.
      Computed tomography (CT) showed a pulmonary nodular shadow in the right middle
      lobe. He was diagnosed with stage cT2aN0M0 (IB) pulmonary adenocarcinoma and was
      treated with surgery of right middle lobectomy and mediastinal lymph node
      dissection. On 2nd day after surgery, he got aspiration pneumonia. CT showed
      consolidation of left lower lobe, stenosis of lower esophagus with dilation of
      the oral side and stagnation of residual foods. Esophagogram showed stenosis of
      the lower esophagus and stagnation of the contrast medium. He was diagnosed with
      esophageal achalasia. Balloon dilation was performed and the obstruction was
      improved. He has been well without recurrence of achalasia.

PMID- 30185742
TI  - [Antineutrophil Cytoplasmic Antibody (ANCA) Negative Limited-form Granulomatosis
      with Polyangiitis of the Lung Diagnosed by the Thoracoscopic Lung Biopsy].
AB  - Antineutrophil cytoplasmic antibody (ANCA) negative pulmonary limited-form
      granulomatous with polyangiitis (GPA) is a rare type of GPA. A 53-year-old female
      had been followed as the possible pulmonary infarction of bilateral lungs for 4
      years without any therapy. Chest computed tomography(CT) examination of the
      patient showed newly appeared nodular lesions in the lungs, which were suspected
      as malignancy by positron emission tomography (PET) -CT. Thoracoscopic lung
      biopsy of the lesions was performed and histopathological diagnosis was GPA
      showing multiple granulomas with vasculitis. Since both C and P-ANCA were
      negative and no evidence of kidney involvement, we finally diagnosed the lung
      lesions as ANCA negative limited-form GPA.

PMID- 30185744
TI  - [Concurrent Mitral and Tricuspid Valve Surgery in a Patient with Left Collapsed
      Lung;Report of a Case].
AB  - A 77-year-old man was referred to our hospital with severe mitral valve
      regurgitation. Secondary to left partial lobectomy for tuberculosis 55 years
      earlier, his mediastinum was shifted to the left, and his pulmonary function was
      moderately decreased. Mitral valve replacement and tricuspid annuloplasty were
      performed with a median sternotomy. Although the heart was shifted to the left,
      the mitral valve was easily visualized when the right side of the pericardium was
      extensively elevated. The tracheal intubation tube was removed 1 day after the
      operation. The patient's postoperative course was uneventful, and he was
      discharged on the 13th postoperative day. We describe our surgical strategy in
      this patient with a literature review.

PMID- 30185743
TI  - [Simultaneous Transapical Transcatheter Aortic Valve Implantation and Coronary
      Artery Bypass Grafting;Report of a Case].
AB  - Coronary artery disease(CAD) is often found concurrently in patients presenting
      with severe aortic stenosis(AS). Surgical aortic valve replacement(SAVR) and
      coronary artery bypass grafting(CABG) were usually selected with such patients.
      Recently, transcatheter aortic valve implantation (TAVI) is considered as a less
      invasive and more feasible treatment option in high-risk AS patients. A 74-year
      old woman admitted due to acute myocardial infarction and treated with
      percutaneous coronary intervention revealed severe AS. Because of her
      comorbidities, concomitant transapical TAVI and CABG were performed with an
      excellent clinical course.

PMID- 30185745
TI  - [Staged Hybrid Treatment for a Coronary Artery Pseudoaneurysm after Percutaneous
      Coronary Intervention;Report of a Case].
AB  - We herein report a case of a coronary artery pseudoaneurysm caused by previous
      catheter intervention, who was treated with a staged hybrid procedure of coronary
      artery bypass grafting (CABG) and subsequent percutaneous catheter intervention.
      A 59-year-old man underwent an urgent percutaneous coronary stent placement for
      acute myocardial infarction at segment 1 of the right coronary artery, where
      later coronary pseudoaneurysm developed. Prior to closure of the aneurysm by
      covered stent placement, he underwent CABG to segment 3 using the right internal
      thoracic artery graft, in case the implanted covered stent should acutely
      thrombose in the future. The graft flow was increased by producing an artificial
      stenosis just proximal to the anastomosis. The present technique would be a safe
      and viable option of therapeutic strategy to fix coronary artery pseudoaneurysms
      that have been formed at the proximal segment of main coronary arteries.

PMID- 30185746
TI  - [Papillary Fibroelastoma of the Left Ventricular Outflow Tract;Report of a Case].
AB  - Papillary fibroelastoma(PFE) is a rare and benign primary cardiac neoplasm. The
      incidence of PFE in the left ventricle is lower than that in other parts of the
      heart. A 67-year-old female was referred to our cardiology department for
      treatment of severe cardiac failure due to mitral regurgitation. Transthoracic
      and transesophageal echocardiography coincidently revealed a 1.0 cm highly mobile
      mass attached by a stalk to the outflow tract wall of the left ventricle. The
      mass was easily detected using endoscope and successfully removed without any
      postoperative complications and was pathologically diagnosed as a PFE. In this
      report, we discuss the echocardiographic character of PFE and the usefulness of
      endoscope for the identification and resection of a PFE in the left ventricle.

PMID- 30185747
TI  - [Spontaneous Rupture of the Ascending Aorta;Report of a Case].
AB  - A 66-year-old woman was transferred to our hospital on an emergency basis
      complaining of a sudden onset of chest discomfort. An emergency contrasted
      computed tomography showed a ruptured the ascending aorta near the right
      pulmonary artery with a hematoma and notch in the aortic wall. An emergency
      operation of the graft replacement was performed via standard median sternotomy
      under the cardiac arrest with aortic clamp. Upon the operation, there was a 1.5
      cm rupture site in the central portion of the ascending aorta. There was no
      specific evidence of aortic aneurysm or dissection, therefore a spontaneous
      rupture of the ascending aorta was diagnosis. The pathological finding was normal
      without pathological changes of cystic medial necrosis or atheroma. The
      postoperative course was uneventful and he was discharged 14 days after surgery.

PMID- 30185748
TI  - [Thoracic Aortic Injury after Spinal Fusion;Report of a Case].
AB  - A 32-year-old female visited our hospital with back pain. She had undergone
      spinal fusion for scoliosis at another hospital. She visited our hospital because
      she was informed that the metal rod had broken. Computed tomography(CT) revealed
      a suspected penetration of one of the screws into the descending aorta, and
      aortography showed the aortic wall dented by the screw. The aorta was exposed via
      thoracotomy, and the top of the screw was found penetrating into the adventitia
      of the aorta. After carefully detaching the region from the screw, the defect of
      the adventitia was repaired by continuous suture. The screw was cut to avoid
      further injury. Several days later, re-operation was successfully performed for
      the scoliosis.

PMID- 30185749
TI  - [Solitary Pulmonary Metastasis from Carcinoma of the Ampulla of Vater after
      Pancreatoduodenectomy;Report of a Case].
AB  - A 74-year-old woman had underwent pancreatoduodenectomy for a carcinoma of the
      ampulla of Vater. After 3 years of the operation, chest computed tomography (CT)
      scan showed a solitary nodule in the right posterior segment (S2). Under the
      diagnosis of solitary pulmonary metastasis, we performed wedge resection for the
      right S2 lesion under video-assisted thoracic surgery (VATS). Pathological
      diagnosis was the metastasis of carcinoma of the ampulla of Vater. One year
      later, chest CT scan showed another solitary lesion in right superior segment
      (S6). Wedge resection was performed again for the right S6 nodule, which was also
      diagnosed as a metastasis.

PMID- 30185750
TI  - [Pulmonary Non-tuberculous Mycobacteriosis Complicated with Pulmonary Large Cell
      Neuroendocrine Carcinoma;Report of a Case].
AB  - A 64-year-old man with pulmonary non-tuberculous mycobacteriosis(pulmonary NTM)
      who had been treated by antituberculous chemotherapy, developed a new nodule of 8
      mm in size in the segment 3 of the right upper lobe. The cavity of 4.0 cm in size
      in the segment 1+2 of the left upper lobe due to Mycobacterium avium infection
      was preexisted. Radiologically, new nodule of the right lung was suspected to be
      lung cancer. Left upper lobe apical trisegmentectomy was performed at first.
      Three months later, enlarging of the right lung nodule with increased fluoro-2
      deoxy-D-glucose(FDG) activity was noted, and the diagnosis of lung cancer was
      made by transbronchial lung biopsy(TBLB). Then, right upper lobectomy with
      systematic nodal dissection were performed.

PMID- 30185751
TI  - [Elastofibroma Dorci;Report of a Case].
AB  - Elastofibroma is a relatively rare tumor that occurs commonly at the apex of
      scapula in elderly people. We report a case of elastofibroma of a female in her
      seventies. She visited our hospital with complaints of painful mass in her back,
      which was increasing in size. On the magnetic resonance imaging (MRI),the T1 and
      the T2-weighted images showed the same signal intensity as the muscle between the
      right scapula and the intercostal muscles. The internal fat component was cord
      like, with high signal intensity. Based on the site of the tumor and
      characteristic findings on imaging, it was diagnosed as elastofibroma and
      resection was performed. Pathological findings revealed bundle-like proliferation
      of fibrous and spherical hyaline substances, together with collagen fibers. The
      hyaline substance stained in black on Elastica van Gieson staining and was
      confirmed to be elastic fiber. Thus, it was diagnosed as elastofibroma. The
      patient is on regular follow-up, with no recurrence after surgery.

PMID- 30185752
TI  - [Induction Chemoradiothorapy Followed by Surgery in Non-small-cell Lung Cancer;a
      Retrospective Study].
AB  - OBJECTIVE: The aim of this study is to investigate the outcomes of induction
      chemoradiotherapy (ICRT) followed by surgery in patients with non-small cell lung
      cancer( NSCLC). METHODS: We retrospectively analyzed consecutive patients with
      NSCLC who underwent ICRT followed by surgery at our hospital between January 2006
      and December 2015. RESULTS: A total of 102 patients were eligible for evaluation
      (cStage/I B/II A/II B/III A/III B, 1/8/14/75/4). The median age was 66 years.
      Forty-one patients had adenocarcinoma, 42 patients had squamous cell carcinoma,
      and 19 patients had others. The regimen consisted of carboplatin and paclitaxel
      in 94 patients, and the others in 8 patients plus concurrent radiation at a dose
      of 28 Gy in 1 patient, 30 Gy in 28 patients, 40 Gy in 42 patients, 45 Gy in 3
      patients, and 50 Gy in 28 patients. Major response was obtained in 84 patients.
      Grade 3/4 toxicity of ICRT reported in 57 patients. The 5-year relapse-free and
      overall survival rate was 51.4% and 62.7%, respectively. CONCLUSION: ICRT
      (carboplatin and paclitaxel plus concurrent standard radiation) followed by
      surgery in NSCLC can be safely performed and may contribute to satisfactory
      outcomes in locally advanced NSCLC. It is likely that 28~50 Gy radiation dose
      contributes to satisfactory outcomes in ICRT.

PMID- 30185753
TI  - [Wedge Bronchoplastic Left Upper Lobectomy for Lung Cancer Patient with Abnormal
      Mediastinal Left Basal Pulmonary Artery].
AB  - A 65-year-old man with left lung squamous cell carcinoma was admitted to our
      hospital for operation. His tumor was located left upper lobe and invaded to the
      orifice of left upper bronchus. We diagnosed the tumor as cT2aN0M0 and intended
      to perform radical operation. Preoperative three-dimensional computed tomography
      (3D-CT) revealed that A9+10 which descended along lower bronchus was arisen from
      the left main pulmonary artery as a 1st branch of it. A wedge bronchoplastic left
      upper lobectomy was safely done with preserving the branch. Although this
      abnormal branching of left pulmonary artery is very rare, we should pay more
      attention this type of anomaly because unintended injury of the branch causes
      massive bleeding or ischemia of left lower lobe. Preoperative 3D-CT is useful for
      detecting the anomaly of pulmonary vessels.

PMID- 30185754
TI  - [Full Sternotomy with Lower Skin Incision for Coronary Artery Bypass Grafting
      with Permanent Tracheostomy].
AB  - A 68-year-old man who previously underwent a permanent tracheostomy was referred
      to us for coronary artery bypass grafting(CABG). Off-pump CABG was successfully
      performed with full sternotomy through a limited skin incision. The postoperative
      course was uneventful. This technique seemed useful for a patient with permanent
      tracheostomy who is scheduled for CABG. Preoperative computed tomography(CT) scan
      was useful for the assessment of this procedure.

PMID- 30185755
TI  - [Clinical Efficacy of Prone Positioning in Elderly Patients with Respiratory
      Failure after Thoracic Aortic Surgery].
AB  - In order to demonstrate the clinical efficacy of prone positioning(PP), we
      reviewed 2 elderly patients with respiratory failure who underwent thoracic
      aortic surgery. Case 1:An 80-year-old man with true thoracic aortic aneurysm
      (TAA) underwent total arch replacement under moderate hypothermia. Two days after
      surgery, PP was conducted for 3 hours to treat atelectasis and poor oxygenation.
      His respiratory state and oxygenation subsequently improved and he was weaned
      from ventilator assistance. Case 2:An 82-year-old woman with early thrombosed
      acute type A aortic dissection and cardiac tamponade underwent emergency primary
      repair of the ascending aorta under moderate hypothermia. Six days after surgery,
      PP was conducted for approximately 3 hours to improve oxygenation. She was weaned
      from the ventilator 7 days after surgery. The clinical courses of both cases
      after PP were uneventful. In order to improve the respiratory state of elderly
      patients after TAA surgery, PP is effective and useful.

PMID- 30185756
TI  - [Combined Thoraco-abdominal Aortic Aneurysm Repair and Coronary Artery Bypass
      Grafting through a Left Thoracotomy].
AB  - Approximately 40% of the patients with aortic aneurysm have coronary artery
      disease(CAD), which is an important factor contributing to early mortality
      associated with aneurysm surgery. Combined coronary artery bypass grafting
      (CABG)and aortic aneurysm repair of the ascending aorta to the aortic arch is
      often performed through a median sternotomy due to a good surgical exposure.
      However, treatment strategy of thoraco-abdominal aortic aneurysm(TAAA) combined
      with CAD is often controversial. We report a successful case of a 69-year-old man
      who underwent TAAA repair and CABG through a left thoracotomy. Left thoracotomy
      via the 5th intercostal space with para-rectal incision provides a good surgical
      exposure of the thoraco-abdominal aorta and the left anterior descending
      artery(LAD). LAD was revascularized with a saphenous vein graft which was
      anastomosed to the descending aorta, followed by TAAA repair. The postoperative
      course was uneventful and the patient was discharged on 13th postoperative day
      without any complications.

PMID- 30185757
TI  - [Typical Carcinoid of the Lung with Abnormal Elevation of Serum Pro-gastrin
      releasing Peptide (ProGRP)].
AB  - A 40-year-old male was referred to our hospital because of a nodular shadow
      detected in the left lower lobe with the tendency to increase gently. Because
      fluoro-2-deoxy-D-glucose (FDG) uptake was extremely low on a FDG positron
      emission tomography (PET-CT), the tumor was highly suspected of the benign tumor.
      Five years later, a follow-up computed tomography (CT) showed the shadow to be
      enlarged. FDG uptake was changed to be high, and serum level of pro-gastrin
      releasing peptide (Pro-GRP) was extremely elevated. Surgical treatment was chosen
      under suspicious diagnosis of neuroendocrine tumor, such as small cell carcinoma,
      large cell neuroendocrine carcinoma, and carcinoid. By the intraoperative
      aspiration cytology, a small cell carcinoma or a carcinoid was suspected and left
      lower lobectomy with systemic lymph node dissection was performed. The final
      histological diagnosis was a typical carcinoid. The elevated serum ProGRP
      immediately decreased to normal postoperatively.

PMID- 30185758
TI  - [Rapidly Developing Pulmonary Cyst Complicated by Pneumothorax Occurred in the
      Early Post-operative Period after Lung Segmentectomy].
AB  - The patient was a 74-year-old man who had undergone surgery for rectal cancer 9
      years before and had developed left lung metastasis(S3)3 years and 4 months prior
      to admission. He had received video assisted left lung wedge resection. He
      presented with a growing nodular lesion close to the remaining left lung margin
      and elevated serum carcinoembryonic antigen(CEA)levels, and underwent open
      extended segmentectomy. The chest drain tube was removed on 3rd post-operative
      day, but he developed left pneumothorax on 4th post-operative day and a computed
      tomography(CT)scan revealed a cystic lesion 5.0 cm in size at the base of his
      left lung. Revision surgery was performed on 8th post-operative day. A pulmonary
      cyst on the diaphragmatic surface of the lung(S10)was found and location of the
      air leak was confirmed in the same area. Following wedge resection of the cyst
      containing region, the leak ceased completely. Rapid manifestation of a newly
      formed pulmonary cyst during the acute post-operative period is rare.

PMID- 30185759
TI  - [Cor Triatriatum in an Adult Patient Conbined with Mitral Regurgitation and
      Coronary Artery Disease;Report of a Case].
AB  - A 71-year-old female, who had been diagnosed with cor triatriatum 30 years
      before, presented with complains of worsening dyspnea and fatigue. She was
      diagnosed with a combination of cor triatriatum, mitral valve disease and
      coronary artery disease. She underwent removal of the left atrial membrane,
      repair of the mitral valve and coronary artery bypass grafting. This combination
      of cor triatriatum, mitral valve disease and coronary artery disease is
      exceedingly rare. She remains well at 3 years' follow-up.

PMID- 30185760
TI  - [Successful Staged Surgical Management for Double Outlet Right Ventricle with
      Ebstein's Anomaly and Aortic Coarctation;Report of a Case].
AB  - A combination of double outlet right ventricle(DORV) with Ebstein's anomaly and
      aortic coarctation (CoA) is vary rare. We report a successful staged surgical
      repair for DORV with Ebstein's anomaly associated with CoA. The patient had
      subaortic perimembronous ventricular septal defect (10*7.5 mm) and small atrial
      septal defect( 3 mm). Two great arteries were side by side position. The
      posterior leaflet of the tricuspid valve was 10 mm displaced to the right
      ventricle and tricuspid valve regurgitation was severe. The patients was
      unsuitable for primary biventricular repair because the size of the mitral valve
      was considered to be small. First, bilateral pulmonary artery banding was
      performed after balloon atrio-septostomy in the neonatal period. Three months
      after the 1st operation, cardiac catheteraization revealed that the left and
      right heart structure was suitable for biventricular repair. At 4-month-old-age,
      aortic arch reconstruction, intra-cardiac rerouting and tricuspid valve repair
      were performed. Post operative tricuspid valve regurgitation was mild. The
      patient was discharged on the 12th postoperative day with good hemodynamic
      condition.

PMID- 30185761
TI  - [Successful Repair of Acute Aortic Dissection after Stent Placement into the
      Occluded Left Common Carotid Artery;Report of a Case].
AB  - A 63-year old woman was admitted to our hospital due to loss of consciousness
      [Glasgow Coma Scale (GCS) E1V1M4]. Cerebral angiography showed known severe
      stenosis in the right common carotid artery and acute occlusion of the left
      common carotid artery. Enhanced computed tomography(CT) revealed Stanford type A
      acute aortic dissection. We judged an emergency surgery was not indicated for
      this comatose patient. Neurosurgeons placed stents into the left common and
      internal carotid arteries. The next day, the patient regained consciousness (GCS
      E4V2M6), and we performed ascending aorta replacement. There was an intimal tear
      in the ascending aorta and proximal end of the left carotid artery stent was
      visible in the aortic arch. Postoperative course was uneventful, and CT revealed
      successful aortic repair and patent stents in the left carotid artery. She was
      transferred to a rehabilitation hospital on postoperative day 44. Although stent
      insertion into carotid arteries in a patient with acute aortic dissection carries
      some risks such as making a new intimal tear or catheterizing in a false lumen,
      early cerebral reperfusion may improve prognosis of the patients with acute
      aortic dissection with cerebral malperfusion.

PMID- 30185762
TI  - [Acute Aortic Insufficiency due to the Avulsion of Aortic Valve Commissure;Report
      of a Case].
AB  - A 61-year-old man with a history of hypertension and cerebral infarction,
      presented to a clinic with sudden dyspnea at rest. He was diagnosed with heart
      failure and referred to our hospital. Echocardiography and three-dimensional
      computed tomography showed acute heart failure and aortic insufficiency due to
      avulsion of the aortic valve commissure between the right coronary cusp and the
      non-coronary cusp. He had no symptoms such as fever or infection and no history
      of rheumatic disease. He underwent intima fixation of the avulsed commissure and
      aortic valve replacement using a tissue valve because acute left heart failure
      was refractory to medical treatment. Postoperative echocardiography demonstrated
      good left ventricular contraction without any aortic regurgitation. He was
      discharged on the 35th postoperative day.

PMID- 30185763
TI  - [Papillary Fibroelastoma Arising from Chordae Tendineae of the Mitral Valve
      Chordae;Report of a Case].
AB  - Cardiac papillary fibroelastoma is a rare primary cardiac tumor arising from any
      part of the endocardium. In particular, papillary fibroelastoma originating from
      the mitral valve chordae is very rare. A 66-year-old man was hospitalized for a
      left ventricular tumor. Echocardiography revealed a high echoic mass of the
      mitral valve chordae with grade I mitral regurgitation. Under cardiopulmonary
      bypass, we performed excision of the mass and the marginal chordae of the mitral
      valve, and decided there was no need of valvuloplasty. Pathological diagnosis
      indicated the tumor was papillary fibroelastoma. The postoperative course was
      uneventful and echocardiography showed no progression of mitral valve
      regurgitation.

PMID- 30185764
TI  - [Thymoma Showing Elevating Anti-acetylcholine Receptor Antibody without Clinical
      Symptoms of Myasthenia Gravis;Report of a Case].
AB  - A 46-year-old man was referred to our hospital with a suspicion of pericardial
      cyst. Chest computed tomography (CT) revealed an anterior mediastinal tumor. He
      had no symptoms, but laboratory data showed positive titer to acetylcholine
      receptor antibody (Anti-AchR Ab). Under a clinical diagnosis of thymoma, extended
      thymectomy was performed. This case may represent subclinical myasthenia gravis,
      so we suggest extended thymectomy is crucial for thymoma with elevated level of
      Anti-AchR Ab without any symptoms.

PMID- 30185765
TI  - [Primary Pulmonary Synovial Sarcoma;Report of a Case].
AB  - A 66-year-old man was referred to our hospital for an abnormal shadow. Chest
      computed tomography (CT)showed a heterogeneous mass with well-defined border in
      the right S10and ipsilateral pleural effusion. Fluorodeoxyglucose-positron
      emission tomography(FDG-PET)showed the accumulation in the mass and pleural
      effusion. Right lower lobectomy with lymphnode dissection was performed for
      diagnosis and treatment. Histologically,the tumor was mainly composed of
      complicated spindle-shaped cells with extensive necrosis, showing a large number
      of nuclear fission images. Immunohistochemistry showed the tumor cells to be
      positive for cytokeratin AE1/AE3, Bcl-2, EMA, vimentin and negative for TTF-1, S
      100, calretinin, CD34, being compatible with monophasic fibrous synovial sarcoma.

PMID- 30185766
TI  - Clinical Outcomes and Prognostic Factors in Patients With Myelopathy Caused by
      Thoracic Ossification of the Ligamentum Flavum.
AB  - OBJECTIVE: The objective of this study was to investigate the surgical outcomes
      and prognostic factors for thoracic ossification of the ligamentum flavum (OLF)
      after decompressive laminectomy, focusing on the quantitative signal intensity
      ratio (SIR) of preoperative magnetic resonance imaging (MRI) and its prognostic
      significance. METHODS: We retrospectively reviewed 24 patients who previously
      underwent total laminectomy to remove OLF from 2010 to 2015. MRI and computed
      tomography were performed to detect OLF. The SIR between the regions of interest
      of high signal intensity lesions and the normal cord at the T1-2 disc levels was
      calculated. We divided patients into 2 groups based on the extent of the modified
      Japanese Orthopaedic Association (JOA) recovery rate (RR): good (RR >= 50%) and
      poor (RR < 50%). RESULTS: The mean preoperative and postoperative modified JOA
      scores for thoracic myelopathy were 6.67 +/- 1.73 and 8.63 +/- 1.81, respectively
      (p < 0.001). The preoperative JOA score (7.5 vs. 5.83, p = 0.028), postoperative
      JOA score (9.83 vs. 7.42, p = 0.000), and SIR (1.16 vs. 1.41, p = 0.009) were
      significantly different between the good and poor RR groups. A higher
      preoperative JOA score and lower SIR were associated with a good RR according to
      the JOA criteria. CONCLUSION: The clinical outcomes for thoracic OLF after
      decompressive laminectomy were favorable. A higher RR was correlated with a lower
      SIR and higher preoperative modified JOA score. Therefore, a relatively low SIR
      on MRI and a relatively high preoperative JOA score could be positive prognostic
      indicators for the JOA RR in patients with thoracic OLF.

PMID- 30185767
TI  - Health Education Using Telephone and WeChat in Treatment of Symptomatic Uterine
      Myoma with High-Intensity Focused Ultrasound.
AB  - BACKGROUND Adopting modern communication methods in traditional healthcare
      services is a trend of modern medicine. In this study we explored the value of
      telephone and WeChat in health education on uterine myoma by high-intensity
      focused ultrasound (HIFU). MATERIAL AND METHODS A total number of 426 patients
      diagnosed with symptomatic uterine myoma from April 2017 to September 2017 were
      selected and randomly divided into a routine preoperative education group (175
      patients) and a telephone/WeChat preoperative health education group (251
      patients). The patients in the routine preoperative education group received
      routine preoperative education, whereas those in the telephone/WeChat
      preoperative health education group received telephone/WeChat preoperative health
      education. Patients were evaluated before and after treatment. RESULTS Compared
      with the routine preoperative education group, the patients in telephone/WeChat
      preoperative health education group had less preoperative and postoperative
      anxiety, less postoperative pain, and higher treatment satisfaction (P<0.05).
      CONCLUSIONS Health education using telephone and WeChat preoperatively can reduce
      preoperative and postoperative anxiety, postoperative pain, and early
      postoperative inflammatory response in patients with uterine myoma, and can
      improve treatment satisfaction.

PMID- 30185768
TI  - Rosiglitazone Reduces Apoptosis and Inflammation in Lipopolysaccharide-Induced
      Human Umbilical Vein Endothelial Cells.
AB  - BACKGROUND Although the peroxisome proliferator-activated receptor-g (PPARg)
      agonist rosiglitazone has significant anti-inflammatory properties, no scientific
      studies have provided new insights in its pharmacological properties with respect
      to acute respiratory distress syndrome (ARDS). The present investigation aimed to
      evaluate whether rosiglitazone can reduce apoptosis and inflammation in a
      lipopolysaccharide (LPS)-induced acute respiratory distress syndrome in vitro
      model. MATERIAL AND METHODS Human umbilical vein endothelial cells (HUVECs) were
      treated with 1 ug/ml LPS in the absence or presence of 10 uM rosiglitazone for 24
      h. Cell viability was measured by MTT assay. Flow cytometry was used to examine
      the cell apoptosis and ROS production in HUVECs response to LPS and
      rosiglitazone. The levels of pro-inflammatory cytokine factors, including TNF
      alpha, IL-6, CXCL12, and CXCR4, were measured by ELISA, real-time PCR, and
      Western blot assay, respectively. The expression of PPARg, Bcl-2, and Bax and the
      activity of JAK2 and STAT3 were also investigated by Western blot assay. RESULTS
      We found that rosiglitazone significantly inhibited LPS-induced cell apoptosis,
      ROS production, and inflammation in HUVECs. Furthermore, we found a significant
      reduction of JAK2/STAT3 activation and the Bax/Bcl-2 ratio in LPS-induced HUVECs
      response to rosiglitazone treatment. CONCLUSIONS Treatment with rosiglitazone can
      reduce apoptosis and inflammation in HUVECs induced by LPS.

PMID- 30185769
TI  - Alleviating Effect of Antidepressant Treatment on Psychiatric Symptoms and
      Cardiac Conditions in a Patient with Coronary Slow Flow Comorbid with Depression
      and Anxiety.
AB  - BACKGROUND Depressive patients are considerably more likely to suffer
      cardiovascular disease (CVD), and in patients with CVD, depression is a predictor
      of poor outcome. Recent findings suggest higher rates of depression and anxiety
      in patients with coronary slow flow (CSF). However, there is no research
      investigating whether the antidepressant treatment can mitigate psychiatric
      symptoms and cardiac conditions in CSF patients comorbid with depression. CASE
      REPORT The patient was a 52-year-old Chinese female with frequent chest pain. The
      patient had serious TIMI (thrombolysis in myocardial infarction) grade 2 flow
      without any coronary stenosis, but comorbid with depression and anxiety. The CSF
      was very likely associated with her mental health condition, given that the chest
      distress and intermittent chest pain followed psychological stress and disturbed
      sleep. Therefore, paroxetine was used under the circumstances of the poor effect
      of cardiovascular active drugs. We found that the adjunctive use of paroxetine
      not only improved the psychiatric symptoms, but also alleviated the cardiac
      conditions. CONCLUSIONS Our findings strengthen the importance of the treatment
      of psychiatric symptoms in patients with CSF and this finding should promote
      randomized controlled trials in a larger population to confirm the beneficial
      effects of antidepressant treatment on psychiatric symptoms and cardiac
      conditions in CSF patients with psycho-cardiac conditions.

PMID- 30185770
TI  - Loss of ATF3 exacerbates liver damage through the activation of mTOR/p70S6K/ HIF
      1alpha signaling pathway in liver inflammatory injury.
AB  - Activating transcription factor 3 (ATF3) is a stress-induced transcription factor
      that plays important roles in regulating immune and metabolic homeostasis.
      Activation of the mechanistic target of rapamycin (mTOR) and hypoxia-inducible
      factor (HIF) transcription factors are crucial for the regulation of immune cell
      function. Here, we investigated the mechanism by which the ATF3/mTOR/HIF-1 axis
      regulates immune responses in a liver ischemia/reperfusion injury (IRI) model.
      Deletion of ATF3 exacerbated liver damage, as evidenced by increased levels of
      serum ALT, intrahepatic macrophage/neutrophil trafficking, hepatocellular
      apoptosis, and the upregulation of pro-inflammatory mediators. ATF3 deficiency
      promoted mTOR and p70S6K phosphorylation, activated high mobility group box 1
      (HMGB1) and TLR4, inhibited prolyl-hydroxylase 1 (PHD1), and increased HIF-1alpha
      activity, leading to Foxp3 downregulation and RORgammat and IL-17A upregulation
      in IRI livers. Blocking mTOR or p70S6K in ATF3 knockout (KO) mice or bone marrow
      derived macrophages (BMMs) downregulated HMGB1, TLR4, and HIF-1alpha and
      upregulated PHD1, increasing Foxp3 and decreasing IL-17A levels in vitro.
      Silencing of HIF-1alpha in ATF3 KO mice ameliorated IRI-induced liver damage in
      parallel with the downregulation of IL-17A in ATF3-deficient mice. These findings
      demonstrated that ATF3 deficiency activated mTOR/p70S6K/HIF-1alpha signaling,
      which was crucial for the modulation of TLR4-driven inflammatory responses and T
      cell development. The present study provides potential therapeutic targets for
      the treatment of liver IRI followed by liver transplantation.

PMID- 30185771
TI  - TRIM52 plays an oncogenic role in ovarian cancer associated with NF-kB pathway.
AB  - Emerging evidence suggests that the members of the tripartite motif (TRIM) family
      play a crucial role in cancer development and progression. The purpose of the
      study was to explore TRIM52's role in tumorigenesis and its potential molecular
      mechanism in ovarian cancer. The study demonstrated that knockdown of TRIM52 in
      SKOV3 and CAOV3 cells inhibited ovarian cancer cell invasion, migration, and
      proliferation, and induced cell apoptosis. On the contrary, overexpression of
      TRIM52 in HO8910 cells showed contrary results. Further, overexpression of TRIM52
      enhanced the expression of phosphorylated IKKbeta and IKBalpha proteins and
      nuclear protein P65, which implied the activation of NF-kB signal pathway.
      Knockdown of TRIM52 downregulated the mRNA and protein levels of NF-kB signal
      downstream effectors of the NF-kB pathway, including MMP9, Bcl2, IL8, and
      TNFalpha, but upregulated caspase-3 expression. These results suggested that
      activation of the NF-kB pathway is involved in TRIM52-mediated regulation in
      ovarian cancer. The nude mice study further confirmed that knockdown of TRIM52
      blocked tumor growth, inhibited cell proliferation, and promoted cell apoptosis.
      Our data strongly suggested that TRIM52 plays an oncogenic role in ovarian cancer
      development associated with the NF-kB signal pathway and may be a potential
      target for cancer therapy.

PMID- 30185772
TI  - Correction to: Natural product pectolinarigenin inhibits osteosarcoma growth and
      metastasis via SHP-1-mediated STAT3 signaling inhibition.
AB  - Since publication of this article, the authors have noticed errors in Fig. 1e
      (the merge image of control group) and Fig. 5e (Pec. 50 mg/kg group). As a result
      of the misfiling of the data, incorrect images were inadvertently inserted in
      Figs. 1e and 5e during figure preparation. The correct figures are given below.

PMID- 30185773
TI  - CD69 enhances immunosuppressive function of regulatory T-cells and attenuates
      colitis by prompting IL-10 production.
AB  - Foxp3+ regulatory T cells (Tregs) can inhibit immune responses and maintain
      immune tolerance by secreting immunosuppressive TGF-beta1 and IL-10. However, the
      efficiency of Tregs become the major obstacle to their use for immunotherapy. In
      this study, we investigated the relevance of the C-type lectin receptor CD69 to
      the suppressive function. Compared to CD4+Foxp3+CD69- Tregs (CD69- Tregs),
      CD4+Foxp3+CD69+ Tregs (CD69+ Tregs) displayed stronger ability to maintain immune
      tolerance. CD69+ Tregs expressed higher levels of suppression-associated markers
      such as CTLA-4, ICOS, CD38 and GITR, and secreted higher levels of IL-10 but not
      TGF-beta1. CD69+ Tregs from Il10+/+ rather than Il10-/- mice significantly
      inhibit the proliferation of CD4+ T cells. CD69 over-expression stimulated higher
      levels of IL-10 and c-Maf expression, which was compromised by silencing of STAT3
      or STAT5. In addition, the direct interaction of STAT3 with the c-Maf promoter
      was detected in cells with CD69 over-expression. Moreover, adoptive transfer of
      CD69+ Tregs but not CD69-Tregs or CD69+ Tregs deficient in IL-10 dramatically
      prevented the development of inflammatory bowel disease (IBD) in mice. Taken
      together, CD69 is important to the suppressive function of Tregs by promoting IL
      10 production. CD69+ Tregs have the potential to develop new therapeutic approach
      for autoimmune diseases like IBD.

PMID- 30185774
TI  - Identification and replication of RNA-Seq gene network modules associated with
      depression severity.
AB  - Genomic variation underlying major depressive disorder (MDD) likely involves the
      interaction and regulation of multiple genes in a network. Data-driven co
      expression network module inference has the potential to account for variation
      within regulatory networks, reduce the dimensionality of RNA-Seq data, and detect
      significant gene-expression modules associated with depression severity. We
      performed an RNA-Seq gene co-expression network analysis of mRNA data obtained
      from the peripheral blood mononuclear cells of unmedicated MDD (n = 78) and
      healthy control (n = 79) subjects. Across the combined MDD and HC groups, we
      assigned genes into modules using hierarchical clustering with a dynamic tree cut
      method and projected the expression data onto a lower-dimensional module space by
      computing the single-sample gene set enrichment score of each module. We tested
      the single-sample scores of each module for association with levels of depression
      severity measured by the Montgomery-Asberg Depression Scale (MADRS). Independent
      of MDD status, we identified 23 gene modules from the co-expression network. Two
      modules were significantly associated with the MADRS score after multiple
      comparison adjustment (adjusted p = 0.009, 0.028 at 0.05 FDR threshold), and one
      of these modules replicated in a previous RNA-Seq study of MDD (p = 0.03). The
      two MADRS-associated modules contain genes previously implicated in mood
      disorders and show enrichment of apoptosis and B cell receptor signaling. The
      genes in these modules show a correlation between network centrality and
      univariate association with depression, suggesting that intramodular hub genes
      are more likely to be related to MDD compared to other genes in a module.

PMID- 30185775
TI  - Disruption of Tmem30a results in cerebellar ataxia and degeneration of Purkinje
      cells.
AB  - Phospholipids are asymmetrically distributed across mammalian plasma membrane
      with phosphatidylserine (PS) and phosphatidylethanolamine concentrated in the
      cytoplasmic leaflet of the membrane bilayer. This asymmetric distribution is
      dependent on a group of P4-ATPases named PS flippases. The proper transport and
      function of PS flippases require a beta-subunit transmembrane protein 30 A
      (TMEM30A). Disruption of PS flippases led to several human diseases. However, the
      roles of TMEM30A in the central nervous system remain elusive. To investigate the
      role of Tmem30a in the cerebellum, we developed a Tmem30a Purkinje cell (PC)
      specific knockout (KO) mouse model. The Tmem30a KO mice displayed early-onset
      ataxia and progressive PC death. Deficiency in Tmem30a led to an increased
      expression of Glial fibrillary acidic protein and astrogliosis in regions with PC
      loss. Elevated C/EBP homologous protein and BiP expression levels indicated the
      presence of endoplasmic reticulum stress in the PCs prior to visible cell loss.
      Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) analysis
      suggested that apoptotic cell death occurred in the cerebellum. Our data
      demonstrate that loss of Tmem30a in PCs results in protein folding and transport
      defects, a substantial decrease in dendritic spine density, increased
      astrogliosis and PC death. Taken together, our data demonstrate an essential role
      of Tmem30a in the cerebellum PCs.

PMID- 30185776
TI  - SARS-Coronavirus Open Reading Frame-3a drives multimodal necrotic cell death.
AB  - The molecular mechanisms underlying the severe lung pathology that occurs during
      SARS-CoV infections remain incompletely understood. The largest of the SARS-CoV
      accessory protein open reading frames (SARS 3a) oligomerizes, dynamically
      inserting into late endosomal, lysosomal, and trans-Golgi-network membranes.
      While previously implicated in a non-inflammatory apoptotic cell death pathway,
      here we extend the range of SARS 3a pathophysiologic targets by examining its
      effects on necrotic cell death pathways. We show that SARS 3a interacts with
      Receptor Interacting Protein 3 (Rip3), which augments the oligomerization of SARS
      3a helping drive necrotic cell death. In addition, by inserting into lysosomal
      membranes SARS 3a triggers lysosomal damage and dysfunction. Consequently,
      Transcription Factor EB (TFEB) translocates to the nucleus increasing the
      transcription of autophagy- and lysosome-related genes. Finally, SARS 3a
      activates caspase-1 either directly or via an enhanced potassium efflux, which
      triggers NLRP3 inflammasome assembly. In summary, Rip3-mediated oligomerization
      of SARS 3a causes necrotic cell death, lysosomal damage, and caspase-1 activation
      all likely contributing to the clinical manifestations of SARS-CoV infection.

PMID- 30185777
TI  - Mechanism and disease implications of necroptosis and neuronal inflammation.

PMID- 30185778
TI  - Adenylate kinase potentiates the capsular polysaccharide by modulating Cps2D in
      Streptococcus pneumoniae D39.
AB  - Streptococcus pneumoniae is a polysaccharide-encapsulated bacterium. The capsule
      thickens during blood invasion compared with the thinner capsules observed in
      asymptomatic nasopharyngeal colonization. However, the underlying mechanism
      regulating differential CPS expression remains unclear. CPS synthesis requires
      energy that is supplied by ATP. Previously, we demonstrated a correlation between
      ATP levels and adenylate kinase in S. pneumoniae (SpAdK). A dose-dependent
      induction of SpAdK in serum was also reported. To meet medical needs, this study
      aimed to elucidate the role of SpAdK in the regulation of CPS production. CPS
      levels in S. pneumoniae type 2 (D39) increased proportionally with SpAdK levels,
      but they were not related to pneumococcal autolysis. Moreover, increased SpAdK
      levels resulted in increased total tyrosine kinase Cps2D levels and
      phosphorylated Cps2D, which is a regulator of CPS synthesis in the D39 strain.
      Our results also indicated that the SpAdK and Cps2D proteins interact in the
      presence of Mg-ATP. In addition, in silico analysis uncovered the mechanism
      behind this protein-protein interaction, suggesting that SpAdK binds with the
      Cps2D dimer. This established the importance of the ATP-binding domain of Cps2D.
      Taken together, the biophysical interaction between SpAdK and Cps2D plays an
      important role in enhancing Cps2D phosphorylation, which results in increased CPS
      synthesis.

PMID- 30185779
TI  - Alcohol-induced autophagy via upregulation of PIASy promotes HCV replication in
      human hepatoma cells.
AB  - Both alcohol and hepatitis C virus (HCV) infection could induce cellular
      autophagy in liver cells, which is considered to be essential for productive HCV
      replication. However, whether alcohol-induced autophagy is involved in the
      pathogenesis of HCV infection is still poorly understood. Alcohol treatment could
      induce autophagy in Huh7 cells (a hepatoma cell line that supports HCV JFH-1
      replication), evidenced by the increase of LC3B-II levels, the conversion of LC3B
      I to LC3B-II, and the formation of GFP-LC3 puncta as well as the decrease of p62
      level in alcohol-treated cells compared with control cells. Alcohol treatment
      also significantly increased PIASy (a member of the PIAS family) expression,
      which can act as a SUMO (small ubiquitin-like modifier protein) E3 ligase to
      regulate a broader range of cellular processes including autophagy.
      Overexpression or the silencing expression of PIASy in alcohol-treated Huh7 cells
      could increase or decrease autophagic activation caused by alcohol treatment,
      respectively, and thus affect HCV replication correspondingly. In the absence of
      alcohol, overexpression or silencing expression of PIASy increase or decrease the
      level of cellular autophagy, judged by the changes of LC3B-II and p62 levels in
      the presence or absence of chloroquine (CQ), a lysosome inhibitor. More
      importantly, in the presence of 3-methyladenine (3-MA), an inhibitor in the early
      stage of autophagy, the effects of overexpression or silencing expression of
      PIASy on HCV replication were largely blocked. Furthermore, PIASy could
      selectively drive the accumulation of SUMO1-conjugated proteins, along with
      upregulation of the expression of several important autophagy factors, including
      ATG7 and ATG5-ATG12. In conclusion, alcohol promotes HCV replication through
      activation of autophagy in Huh7 cells, which partly attributes to its induction
      of PIASy expression. PIASy-enhanced accumulation of SUMO1-conjugated proteins may
      contribute to its inducing effect of autophagy. Our findings provide a novel
      mechanism for the action of alcohol-promoting HCV replication in the context of
      cellular autophagy.

PMID- 30185781
TI  - Downregulation of the long noncoding RNA MBNL1-AS1 protects sevoflurane
      pretreated mice against ischemia-reperfusion injury by targeting KCNMA1.
AB  - Total knee arthroplasty (TKA) is the most common and cost-effective treatment for
      older adults with long-standing osteoarthritis. During TKA, muscle cells suffer
      from prolonged oxygen deficiency, which leads to altered cell metabolism that
      reduces the energy demand and maintains cell homeostasis before blood flow is
      restored. This study focused on the role of the lncRNA muscleblind-like 1
      antisense RNA 1 (MBNL1-AS1) in protecting sevoflurane-pretreated mice against
      ischemia-reperfusion (I/R) injury after TKA, as well as the elucidation of the
      potential associated mechanism. Identification of differentially expressed
      lncRNAs was performed using the microarray dataset GSE21164, which was extracted
      from the GEO database. Target genes of the lncRNA were determined using Multi
      Experiment Matrix (MEM), a dual-luciferase reporter gene assay, and KEGG
      enrichment analyses. The results showed that MBNL1-AS1 was overexpressed in
      skeletal muscle cells in mice, while KCNMA1, which was enriched in the cGMP-PKG
      signaling pathway, was negatively regulated by MBNL1-AS1. Furthermore, I/R mice
      displayed serious inflammatory reactions. Down-regulation of MBNL1-AS1 increased
      the expression of KCNMA1, PKGII, VASP, VEGF, Bcl-2, Cyclin D1, Cyclin D3, and Cdc
      42 but decreased the expression of Bax, cleaved caspase-3, and cleaved PARP.
      Furthermore, upon MBNL1-AS1 upregulation, the rate of cell apoptosis increased
      while the rate of cell proliferation decreased. Our data suggested that down
      regulated lncRNA MBNL1-AS1 might promote the proliferation and inhibit the
      apoptosis of skeletal muscle cells by upregulating KCNMA1 expression via
      activation of the cGMP-PKG signaling pathway, thus protecting sevoflurane
      pretreated mice against I/R injury after TKA.

PMID- 30185780
TI  - A gene co-expression module implicating the mitochondrial electron transport
      chain is associated with long-term response to lithium treatment in bipolar
      affective disorder.
AB  - Lithium is the first-line treatment for bipolar affective disorder (BPAD) but two
      thirds of patients respond only partially or not at all. The reasons for this
      high variability in lithium response are not well understood. Transcriptome-wide
      profiling, which tests the interface between genes and the environment,
      represents a viable means of exploring the molecular mechanisms underlying
      lithium response variability. Thus, in the present study we performed co
      expression network analyses of whole-blood-derived RNA-seq data from n = 50
      lithium-treated BPAD patients. Lithium response was assessed using the well
      validated ALDA scale, which we used to define both a continuous and a dichotomous
      measure. We identified a nominally significant correlation between a co
      expression module comprising 46 genes and lithium response represented as a
      continuous (i.e., scale ranging 0-10) phenotype (cor = -0.299, p = 0.035). Forty
      three of these 46 genes had reduced mRNA expression levels in better lithium
      responders relative to poorer responders, and the central regulators of this
      module were all mitochondrially-encoded (MT-ND1, MT-ATP6, MT-CYB). Accordingly,
      enrichment analyses indicated that genes involved in mitochondrial functioning
      were heavily over-represented in this module, specifically highlighting the
      electron transport chain (ETC) and oxidative phosphorylation (OXPHOS) as affected
      processes. Disrupted ETC and OXPHOS activity have previously been implicated in
      the pathophysiology of BPAD. Our data adds to previous evidence suggesting that a
      normalisation of these processes could be central to lithium's mode of action,
      and could underlie a favourable therapeutic response.

PMID- 30185782
TI  - BH3 mimetics induce apoptosis independent of DRP-1 in melanoma.
AB  - Despite the recent advancement in treating melanoma, options are still limited
      for patients without BRAF mutations or in relapse from current treatments. BH3
      mimetics against members of the BCL-2 family have gained excitement with the
      recent success in hematological malignancies. However, single drug BH3 mimetic
      therapy in melanoma has limited effectiveness due to escape by the anti-apoptotic
      protein MCL-1 and/or survival of melanoma-initiating cells (MICs). We tested the
      efficacy of the BH3 mimetic combination of A-1210477 (an MCL-1 inhibitor) and ABT
      263 (a BCL-2/BCL-XL/BCL-W inhibitor) in killing melanoma, especially MICs. We
      also sought to better define Dynamin-Related Protein 1 (DRP-1)'s role in
      melanoma; DRP-1 is known to interact with members of the BCL-2 family and is a
      possible therapeutic target for melanoma treatment. We used multiple assays (cell
      viability, apoptosis, bright field, immunoblot, and sphere formation), as well as
      the CRISPR/Cas9 genome-editing techniques. For clinical relevance, we employed
      patient samples of different mutation status, including some relapsed from
      current treatments such as anti-PD-1 immunotherapy. We found the BH3 mimetic
      combination kill both the MICs and non-MICs (bulk of melanoma) in all cell lines
      and patient samples irrespective of the mutation status or relapsed state (p <
      0.05). Unexpectedly, the major pro-apoptotic proteins, NOXA and BIM, are not
      necessary for the combination-induced cell death. Furthermore, the combination
      impedes the activation of DRP-1, and inhibition of DRP-1 further enhances
      apoptosis (p < 0.05). DRP-1 effects in melanoma differ from those seen in other
      cancer cells. These results provide new insights into BCL-2 family's regulation
      of the apoptotic pathway in melanoma, and suggest that inhibiting the major anti
      apoptotic proteins is sufficient to induce cell death even without involvement
      from major pro-apoptotic proteins. Importantly, our study also indicates that DRP
      1 inhibition is a promising adjuvant for BH3 mimetics in melanoma treatment.

PMID- 30185783
TI  - Polyphyllin I suppresses the formation of vasculogenic mimicry via Twist1/VE
      cadherin pathway.
AB  - Vasculogenic mimicry (VM) is a functional microcirculation pattern formed by
      aggressive tumor cells and is related to the metastasis and poor prognosis of
      many cancer types, including hepatocellular carcinoma (HCC). Thus far, no
      effective drugs have been developed to target VM. In this study, patients with
      liver cancer exhibited reduced VM in tumor tissues after treatment with Rhizoma
      Paridis. Polyphyllin I (PPI), which is the main component of Rhizoma Paridis,
      inhibited VM formation in HCC lines and transplanted hepatocellular carcinoma
      cells. Molecular mechanism analysis showed that PPI impaired VM formation by
      blocking the PI3k-Akt-Twist1-VE-cadherin pathway. PPI also displayed dual effects
      on Twist1 by inhibiting the transcriptional activation of the Twist1 promoter and
      interfering with the ability of Twist1 to bind to the promoter of VE-cadherin,
      resulting in VM blocking. This study is the first to report on the clinical
      application of the VM inhibitor. Results may contribute to the development of
      novel anti-VM drugs in clinical therapeutics.

PMID- 30185784
TI  - Inhibition of TRF2 accelerates telomere attrition and DNA damage in naive CD4 T
      cells during HCV infection.
AB  - T cells play a crucial role in viral clearance and vaccine responses; however,
      the mechanisms that regulate their homeostasis during viral infections remain
      unclear. In this study, we investigated the machineries of T-cell homeostasis and
      telomeric DNA damage using a human model of hepatitis C virus (HCV) infection. We
      found that naive CD4 T cells in chronically HCV-infected patients (HCV T cells)
      were significantly reduced due to apoptosis compared with age-matched healthy
      subjects (HSs). These HCV T cells were not only senescent, as demonstrated by
      overexpression of aging markers and particularly shortened telomeres; but also
      DNA damaged, as evidenced by increased dysfunctional telomere-induced foci (TIF).
      Mechanistically, the telomere shelterin protein, in particular telomeric repeat
      binding factor 2 (TRF2) that functions to protect telomeres from DNA damage, was
      significantly inhibited posttranscriptionally via the p53-dependent Siah-1a
      ubiquitination. Importantly, knockdown of TRF2 in healthy T cells resulted in
      increases in telomeric DNA damage and T-cell apoptosis, whereas overexpression of
      TRF2 in HCV T cells alleviated telomeric DNA damage and T-cell apoptosis. To the
      best of our knowledge, this is the first report revealing that inhibition of TRF2
      promotes T-cell telomere attrition and telomeric DNA damage that accelerates T
      cell senescent and apoptotic programs, which contribute to naive T-cell loss
      during viral infection. Thus, restoring the impaired T-cell telomeric shelterin
      machinery may offer a new strategy to improve immunotherapy and vaccine response
      against human viral diseases.

PMID- 30185785
TI  - Integrin alpha5beta1-Ang1/Tie2 receptor cross-talk regulates brain endothelial
      cell responses following cerebral ischemia.
AB  - We have previously demonstrated that in response to cerebral ischemia (CI), the
      growth factor angiopoietin-1 (Ang1) and alpha5beta1 integrin are both induced in
      cerebral vessels, which likely provide positive signals driving the endogenous
      angiogenic response and vascular protection after CI. However, the precise
      relationship between endothelial Ang1 and alpha5beta1 integrin after CI remains
      poorly understood. Here, we investigated the effects of the interaction between
      the Ang1/Tie2 system and alpha5beta1 integrin on brain endothelial cells (BECs)
      under cerebral ischemic conditions in vivo and in vitro. Immunofluorescence
      analysis demonstrated that integrin alpha5beta1 co-localized with
      Tie2/phosphorylated Tie2 on cerebral vessels in the penumbra. The in vitro study
      showed that oxygen-glucose deprivation/restoration (OGD/R) induced the expression
      of the Ang1 receptor Tie2 on BECs in a manner similar to that for integrin alpha5
      and Ang1 in response to OGD/R, accompanied by increased activation of Tie2 and
      its downstream effectors focal adhesion kinase (FAK) and Akt. Knockdown of alpha5
      integrin markedly suppressed OGD/R-induced Tie2 receptor activation in BECs,
      while in contrast, priming BECs with Ang1 promoted the expression of alpha5
      integrin as well as the Tie2 downstream transcription factor Ets-1 in OGD-treated
      BECs. In line with this, Ets-1 knockdown significantly attenuated Ang1-mediated
      upregulation of alpha5 integrin. Functionally, Ang1 induced cell migration and
      tube formation of BECs after OGD, but this effect was inhibited by diminishment
      of the levels of alpha5 integrin in BECs. Taken together, our data indicate that
      the Ang1/Tie2 system cross-talks with integrin alpha5beta1 in BECs after CI,
      which may contribute to the endogenous angiogenic vascular protective response
      following CI.

PMID- 30185786
TI  - An emerging novel goose astrovirus associated with gosling gout disease, China.
AB  - Since the first isolation from human, astroviruses have been detected in many
      species. Wide host range and occasional cross-transmission of astrovirus pose a
      risk for zoonotic infection. Here, novel astroviruses were identified from
      goslings with recent epidemic gout disease in China. A virus, designated as GD,
      was efficiently isolated from a diseased gosling using LMH cells. Genome of GD
      amplified using 5' and 3' RACE was 7183nt in full length. Sequence analysis
      revealed the genome of GD was <60.8% homology with others deposited in Genbank.
      Moreover, GD could be neutralized by goose convalescent sera, and the gout
      associated symptom in goslings could be reproduced by GD infection. Our data
      demonstrated the goose astrovirus could be one of the causative agents of the
      ongoing gosling gout disease in China. The identification of the goose astrovirus
      not only diversified the astrovirus species, but also broadened the disease
      patterns caused by astroviruses.

PMID- 30185787
TI  - Runx-dependent and silencer-independent repression of a maturation enhancer in
      the Cd4 gene.
AB  - An intronic silencer, S4, in the Cd4 gene has been shown to be responsible for
      the helper-lineage-specific expression of CD4; S4 requires Runx complex binding
      to exert its silencer function against the enhancer-mediated Cd4 activation by
      modulating the epigenetic state of the Cd4 gene. Here we identify a late-acting
      maturation enhancer. Bcl11b plays essential roles for activation of both the
      early-acting proximal enhancer and maturation enhancer of Cd4. Notably, Runx
      complexes suppress these enhancers by distinct mechanisms. Whereas repression of
      the proximal enhancer depends on the S4 silencer, the maturation enhancer is
      repressed by Runx in the absence of S4. Moreover, ThPOK, known to antagonize S4
      mediated Cd4 repression, assists Runx complexes to restrain maturation enhancer
      activation. Distinct modes of S4 silencer action upon distinct enhancers thus
      unravel a pathway that restricts CD4 expression to helper-lineage cells by
      silencer-independent and Runx-dependent repression of maturation enhancer
      activity in cytotoxic-lineage cells.

PMID- 30185788
TI  - TNFalpha sensitizes hepatocytes to FasL-induced apoptosis by NFkappaB-mediated
      Fas upregulation.
AB  - Although it is well established that TNFalpha contributes to hepatitis, liver
      failure and associated hepatocarcinogenesis via the regulation of inflammation,
      its pro-apoptotic role in the liver has remained enigmatic. On its own, TNFalpha
      is unable to trigger apoptosis. However, when combined with the transcriptional
      inhibitor GaLN, it can cause hepatocyte apoptosis and liver failure in mice.
      Moreover, along with others, we have shown that TNFalpha is capable of
      sensitizing cells to FasL- or drug-induced cell death via c-Jun N-terminal kinase
      (JNK) activation and phosphorylation/activation of the BH3-only protein Bim. In
      this context, TNFalpha could exacerbate hepatocyte cell death during simultaneous
      inflammatory and T-cell-mediated immune responses in the liver. Here we show that
      TNFalpha sensitizes primary hepatocytes, established hepatocyte cell lines and
      mouse embryo fibroblasts to FasL-induced apoptosis by the transcriptional
      induction and higher surface expression of Fas via the NFkappaB pathway. Genetic
      deletion, diminished expression or dominant-negative inhibition of the NFkappaB
      subunit p65 resulted in lower Fas expression and inhibited TNFalpha-induced Fas
      upregulation and sensitization to FasL-induced cell death. By hydrodynamic
      injection of p65 shRNA into the tail vein of mice, we confirm that Fas
      upregulation by TNFalpha is also NFkappaB-mediated in the liver. In conclusion,
      TNFalpha sensitization of FasL-induced apoptosis in the liver proceeds via two
      parallel signaling pathways, activation of JNK and Bim phosphorylation and
      NFkappaB-mediated Fas upregulation.

PMID- 30185789
TI  - Precipitation thresholds regulate net carbon exchange at the continental scale.
AB  - Understanding the sensitivity of ecosystem production and respiration to climate
      change is critical for predicting terrestrial carbon dynamics. Here we show that
      the primary control on the inter-annual variability of net ecosystem carbon
      exchange switches from production to respiration at a precipitation threshold
      between 750 and 950 mm yr-1 in the contiguous United States. This precipitation
      threshold is evident across multiple datasets and scales of observation
      indicating that it is a robust result and provides a new scaling relationship
      between climate and carbon dynamics. However, this empirical precipitation
      threshold is not captured by dynamic global vegetation models, which tend to
      overestimate the sensitivity of production and underestimate the sensitivity of
      respiration to water availability in more mesic regions. Our results suggest that
      the short-term carbon balance of ecosystems may be more sensitive to respiration
      losses than previously thought and that model simulations may underestimate the
      positive carbon-climate feedbacks associated with respiration.

PMID- 30185790
TI  - DNA methylation age is accelerated in alcohol dependence.
AB  - Alcohol dependence (ALC) is a chronic, relapsing disorder that increases the
      burden of chronic disease and significantly contributes to numerous premature
      deaths each year. Previous research suggests that chronic, heavy alcohol
      consumption is associated with differential DNA methylation patterns. In
      addition, DNA methylation levels at certain CpG sites have been correlated with
      age. We used an epigenetic clock to investigate the potential role of excessive
      alcohol consumption in epigenetic aging. We explored this question in five
      independent cohorts, including DNA methylation data derived from datasets from
      blood (n = 129, n = 329), liver (n = 92, n = 49), and postmortem prefrontal
      cortex (n = 46). One blood dataset and one liver tissue dataset of individuals
      with ALC exhibited positive age acceleration (p < 0.0001 and p = 0.0069,
      respectively), whereas the other blood and liver tissue datasets both exhibited
      trends of positive age acceleration that were not significant (p = 0.83 and p =
      0.57, respectively). Prefrontal cortex tissue exhibited a trend of negative age
      acceleration (p = 0.19). These results suggest that excessive alcohol consumption
      may be associated with epigenetic aging in a tissue-specific manner and warrants
      further investigation using multiple tissue samples from the same individuals.

PMID- 30185792
TI  - Correction to: The BH3-only protein Bad is dispensable for TNF-mediated cell
      death.
AB  - Since publication of this article, the authors wished to draw attention to an
      error in the materials section as a result of which they have been mis-cited (
      https://www.nature.com/articles/s41422-018-0041-7 ). The dose of TNF given was
      not in fact 15 mg/kg body weight (as stated in the "mouse work" section), but 15
      MUg/kg body weight.

PMID- 30185791
TI  - Combining discovery and targeted proteomics reveals a prognostic signature in
      oral cancer.
AB  - Different regions of oral squamous cell carcinoma (OSCC) have particular
      histopathological and molecular characteristics limiting the standard tumor-node
      metastasis prognosis classification. Therefore, defining biological signatures
      that allow assessing the prognostic outcomes for OSCC patients would be of great
      clinical significance. Using histopathology-guided discovery proteomics, we
      analyze neoplastic islands and stroma from the invasive tumor front (ITF) and
      inner tumor to identify differentially expressed proteins. Potential signature
      proteins are prioritized and further investigated by immunohistochemistry (IHC)
      and targeted proteomics. IHC indicates low expression of cystatin-B in neoplastic
      islands from the ITF as an independent marker for local recurrence. Targeted
      proteomics analysis of the prioritized proteins in saliva, combined with machine
      learning methods, highlights a peptide-based signature as the most powerful
      predictor to distinguish patients with and without lymph node metastasis. In
      summary, we identify a robust signature, which may enhance prognostic decisions
      in OSCC and better guide treatment to reduce tumor recurrence or lymph node
      metastasis.

PMID- 30185794
TI  - A Metalated Porous Porphyrin Polymer with [Co(CO)4]- Anion as an Efficient
      Heterogeneous Catalyst for Ring Expanding Carbonylation.
AB  - The synthesis of beta-lactones from epoxides through ring-expanding carbonylation
      using homogeneous catalysts has received much attention. However, homogeneous
      catalysts suffer from difficulty in product separation and recycling of the
      catalyst, limiting their industrial usage. Herein, a novel heterogeneous
      catalyst, [Cr-metalated porous porphyrin polymer]+[Co(CO)4]-, was prepared and
      used for the conversion of propylene oxide (PO) to beta-butyrolactone; this
      catalyst presented superior catalytic activity and selectivity (99%) than our
      previous heterogeneous catalyst. In addition, the catalyst was readily separated
      from the product without significant loss of catalytic activity. A possible
      method to recover the original catalytic activity also was demonstrated.

PMID- 30185793
TI  - Individual and combined effects of acute delta-9-tetrahydrocannabinol and
      cannabidiol on psychotomimetic symptoms and memory function.
AB  - The main active ingredient in cannabis, delta-9-tetrahydrocannabinol (THC), can
      acutely induce psychotic symptoms and impair episodic and working memory. Another
      major constituent, cannabidiol (CBD), may attenuate these effects. This study
      aimed to determine the effects of THC and CBD, both alone and in combination on
      psychotic symptoms and memory function. A randomised, double-blind crossover
      design compared the effects of (i) placebo, (ii) THC 8 mg, (iii) CBD 16 mg and
      (iv) THC 8 mg + CBD 16 mg administered by inhalation through a vaporiser. Using
      an experimental medicine approach to predict treatment sensitivity, we selected
      48 cannabis users from the community on the basis of (1) schizotypal personality
      questionnaire scores (low, high) and (2) frequency of cannabis use (light,
      heavy). The Brief Psychiatric Rating Scale (BPRS), Psychotomimetic States
      Inventory (PSI), immediate and delayed prose recall (episodic memory), 1- and 2
      back (working memory) were assessed on each day. Results indicated that THC
      increased overall scores on the PSI, negative symptoms on BPRS, and robustly
      impaired episodic and working memory. Co-administration of CBD did not attenuate
      these effects. CBD alone reduced PSI scores in light users only. At a ratio of
      2:1, CBD does not attenuate the acute psychotic and memory impairing effects of
      vaporised THC. Frequent cannabis users may show a blunted anti- psychotic
      response to CBD, which is of concern due to the high rates of cannabis use
      disorders in patients with schizophrenia.

PMID- 30185796
TI  - Morphodynamic evolution following sediment release from the world's largest dam
      removal.
AB  - Sediment pulses can cause widespread, complex changes to rivers and coastal
      regions. Quantifying landscape response to sediment-supply changes is a long
      standing problem in geomorphology, but the unanticipated nature of most sediment
      pulses rarely allows for detailed measurement of associated landscape processes
      and evolution. The intentional removal of two large dams on the Elwha River
      (Washington, USA) exposed ~30 Mt of impounded sediment to fluvial erosion,
      presenting a unique opportunity to quantify source-to-sink river and coastal
      responses to a massive sediment-source perturbation. Here we evaluate geomorphic
      evolution during and after the sediment pulse, presenting a 5-year sediment
      budget and morphodynamic analysis of the Elwha River and its delta. Approximately
      65% of the sediment was eroded, of which only ~10% was deposited in the fluvial
      system. This restored fluvial supply of sand, gravel, and wood substantially
      changed the channel morphology. The remaining ~90% of the released sediment was
      transported to the coast, causing ~60 ha of delta growth. Although metrics of
      geomorphic change did not follow simple time-coherent paths, many signals peaked
      1-2 years after the start of dam removal, indicating combined impulse and step
      change disturbance responses.

PMID- 30185795
TI  - Understorey Rhododendron tomentosum and Leaf Trichome Density Affect Mountain
      Birch VOC Emissions in the Subarctic.
AB  - Subarctic vegetation is composed of mountain birch [Betula pubescens ssp.
      czerepanovii (MB)] forests with shrubs and other species growing in the
      understorey. The effects of the presence and density of one understorey shrub,
      Rhododendron tomentosum (RT), on the volatile emissions of MB, were investigated
      in a Finnish subarctic forest site in early and late growing season. Only MB
      trees with an RT-understorey emitted the RT-specific sesquiterpenoids, palustrol,
      ledol and aromadendrene. Myrcene, which is the most abundant RT-monoterpene was
      also emitted in higher quantities by MB trees with an RT-understorey. The effect
      of RT understorey density on the recovery of RT compounds from MB branches was
      evident only during the late season when sampling temperature, as well as RT
      emissions, were higher. MB sesquiterpene and total emission rates decreased from
      early season to late season, while monoterpene emission rate increased. Both RT
      and MB terpenoid emission rates were linked to density of foliar glandular
      trichomes, which deteriorated over the season on MB leaves and emerged with new
      leaves in the late season in RT. We show that sesquiterpene and monoterpene
      compounds emitted by understorey vegetation are adsorbed and re-released by MB,
      strongly affecting the MB volatile emission profile.

PMID- 30185797
TI  - A novel prognostic marker and immunogenic membrane antigen: prohibitin (PHB) in
      pancreatic cancer.
AB  - BACKGROUND: Previous study, using immunoblotting with IgG and membrane proteins,
      identified prohibitin (PHB) as a potential immunogenic membrane antigen. Now,
      investigate PHB expression and biological functions in pancreatic cancer.
      METHODS: PHB expression was analysed in PDAC cell lines, normal pancreas tissues,
      cancer tissues, PDAC patient sera and healthy volunteer sera using QRT-PCR,
      Western blotting, IHC, and ELISA, and a survival analysis and a COX regression
      analysis were performed. Low and high PHB expression levels were accomplished
      using RNA interference technology and gene transfer techniques. Cell
      proliferation, migration, and invasion, apoptosis-related proteins were assessed
      48 h after transfection. RESULTS: PHB was generally expressed in the 8 tested
      PDAC cell lines. PHB was significantly increased in PDAC tissues and negatively
      correlated with overall survival (p < 0.01). PHB was an independent prognostic
      factor in PDAC (p < 0.01). PHB was increased in PDAC patient sera (p < 0.01).
      siRNA-PHB decreased cell growth, migration and invasion. However, PHB
      overexpression resulted in the opposite effects. Western blotting and Flow
      cytometric analysis revealed apoptosis inhibition in siRNA-PHB PDAC cells.
      CONCLUSIONS: PHB plays a key role in modulating the malignant phenotype and
      apoptosis induction, which may be a novel prognostic predictor and a candidate
      for targeted therapy against PDAC.

PMID- 30185798
TI  - Impact of cyber-invasive species on a large ecological network.
AB  - As impacts of introduced species cascade through trophic levels, they can cause
      indirect and counter-intuitive effects. To investigate the impact of invasive
      species at the network scale, we use a generalized food web model, capable of
      propagating changes through networks with a series of ecologically realistic
      criteria. Using data from a small British offshore island, we quantify the
      impacts of four virtual invasive species (an insectivore, a herbivore, a
      carnivore and an omnivore whose diet is based on a rat) and explore which
      clusters of species react in similar ways. We find that the predictions for the
      impacts of invasive species are ecologically plausible, even in large networks.
      Species in the same taxonomic group are similarly impacted by a virtual invasive
      species. However, interesting differences within a given taxonomic group can
      occur. The results suggest that some native species may be at risk from a wider
      range of invasives than previously believed. The implications of these results
      for ecologists and land managers are discussed.

PMID- 30185801
TI  - Evidence for a large Paleozoic Impact Crater Strewn Field in the Rocky Mountains.
AB  - The Earth is constantly bombarded by meteoroids of various sizes. During
      hypervelocity collisions a large amount of energy is coupled to the Earth's
      atmosphere leading to disruption of decimeter to hundred meter-sized meteoroids.
      Smaller meteoroids may form meteorite strewn fields while larger initial bodies
      and high-strength iron meteoroids may form impact crater strewn fields. Impact
      crater strewn fields are ephemeral and none documented to date are older than
      about 63,500 years. Here we report on a newly discovered impact crater strewn
      field, about 280 Myr old, in tilted strata of the Rocky Mountains near Douglas,
      Wyoming. It is the oldest and among the largest of impact crater strewn fields
      discovered to date, extending for a minimum of 7.5 km along a SE-NW trajectory.
      The apparent width of the strewn field is 1.5 km, but the full extent of the
      crater strewn field is not yet constrained owing to restricted exposure. We
      probably see only a small section of the entire crater strewn field. The cascade
      of impacts occurred in an environment that preserved the craters from
      destruction. Shock lithification aided this process.

PMID- 30185799
TI  - Down-regulation of cathepsin S and matrix metalloproteinase-9 via Src, a non
      receptor tyrosine kinase, suppresses triple-negative breast cancer growth and
      metastasis.
AB  - Triple-negative breast cancer (TNBC) is a highly metastatic breast cancer with
      poor prognosis. In the present study, we demonstrated that Src, a non-receptor
      tyrosine kinase, might provide an effective therapeutic strategy to overcome TNBC
      invasion and metastasis, which are mediated via the synergistic action of the
      lysosomal enzyme cathepsin S (CTSS) and gelatinase MMP-9. Knock-down of MMP-9 and
      CTSS using siRNAs resulted in a synergistic suppression of MDA-MB-231 cell
      invasion, which was similarly observed with pharmacological inhibitors. During
      the screening of new drug candidates that suppress both CTSS and MMP-9, BJ-2302,
      a novel 7-azaindolin-2-one derivative, was discovered. Src, an upstream activator
      of both pathways (PI3K/Akt and Ras/Raf/ERK) responsible for the expression of
      CTSS and MMP-9, was identified as a high-affinity target of BJ-2302 (IC90: 3.23
      uM) through a Src kinase assay and a drug affinity responsive target stability
      (DARTS) assay. BJ-2302 effectively suppressed MDA-MB-231 cell invasion (Matrigel
      invasion assay) and metastasis (chorioallantoic membrane assay xenografted with
      MDA-MB-231-luc2-tdTomato cancer cells). Unlike Z-FL-COCHO (potent CTSS
      inhibitor), BJ-2302 did not induce any cytotoxicity in MCF-10A normal breast
      epithelial cells. Additionally, BJ-2302 (1 mg/kg) strongly suppressed TNBC cell
      proliferation in vitro and tumor growth in a xenograft mouse tumor model. The
      anti-metastatic and anti-tumor effects of BJ-2302 were superior to those of Z-FL
      COCHO (1 mg/kg) or batimastat (30 mg/kg), a pan-MMP inhibitor. In summary,
      inhibition of Src kinase suppressed TNBC tumor growth and metastasis, and Src
      inhibitors such as BJ-2302 may constitute a novel therapeutic tool to treat
      breast cancer that expresses high levels of CTSS and MMP-9.

PMID- 30185800
TI  - Ipatasertib, a novel Akt inhibitor, induces transcription factor FoxO3a and NF
      kappaB directly regulates PUMA-dependent apoptosis.
AB  - Colon cancer is one of the three common malignant tumors, with a lower survival
      rate. Ipatasertib, a novel highly selective ATP-competitive pan-Akt inhibitor,
      shows a strong antitumor effect in a variety of carcinoma, including colon
      cancer. However, there is a lack of knowledge about the precise underlying
      mechanism of clinical therapy for colon cancer. We conducted this study to
      determine that ipatasertib prevented colon cancer growth through PUMA-dependent
      apoptosis. Ipatasertib led to p53-independent PUMA activation by inhibiting Akt,
      thereby activating both FoxO3a and NF-kappaB synchronously that will directly
      bind to PUMA promoter, up-regulating PUMA transcription and Bax-mediated
      intrinsic mitochondrial apoptosis. Remarkably, Akt/FoxO3a/PUMA is the major
      pathway while Akt/NF-kappaB/PUMA is the secondary pathway of PUMA activation
      induced by ipatasertib in colon cancer. Knocking out PUMA eliminated ipatasertib
      induced apoptosis both in vitro and in vivo (xenografts). Furthermore, PUMA is
      also indispensable in combinational therapies of ipatasertib with some
      conventional or novel drugs. Collectively, our study demonstrated that PUMA
      induction by FoxO3a and NF-kappaB is a critical step to suppress the growth of
      colon cancer under the therapy with ipatasertib, which provides some theoretical
      basis for clinical assessment.

PMID- 30185802
TI  - Attending to Visual Stimuli versus Performing Visual Imagery as a Control
      Strategy for EEG-based Brain-Computer Interfaces.
AB  - Currently the most common imagery task used in Brain-Computer Interfaces (BCIs)
      is motor imagery, asking a user to imagine moving a part of the body. This study
      investigates the possibility to build BCIs based on another kind of mental
      imagery, namely "visual imagery". We study to what extent can we distinguish
      alternative mental processes of observing visual stimuli and imagining it to
      obtain EEG-based BCIs. Per trial, we instructed each of 26 users who participated
      in the study to observe a visual cue of one of two predefined images (a flower or
      a hammer) and then imagine the same cue, followed by rest. We investigated if we
      can differentiate between the different subtrial types from the EEG alone, as
      well as detect which image was shown in the trial. We obtained the following
      classifier performances: (i) visual imagery vs. visual observation task (71% of
      classification accuracy), (ii) visual observation task towards different visual
      stimuli (classifying one observation cue versus another observation cue with an
      accuracy of 61%) and (iii) resting vs. observation/imagery (77% of accuracy
      between imagery task versus resting state, and the accuracy of 75% between
      observation task versus resting state). Our results show that the presence of
      visual imagery and specifically related alpha power changes are useful to broaden
      the range of BCI control strategies.

PMID- 30185804
TI  - Operation Mechanism of GaN-based Transistors Elucidated by Element-Specific X-ray
      Nanospectroscopy.
AB  - With the rapid depletion of communication-frequency resources, mainly due to the
      explosive spread of information communication devices for the internet of things,
      GaN-based high-frequency high-power transistors (GaN-HEMTs) have attracted
      considerable interest as one of the key devices that can operate in the high
      frequency millimeter-wave band. However, GaN-HEMT operation is destabilized by
      current collapse phenomena arising from surface electron trapping (SET), which
      has not been fully understood thus far. Here, we conduct quantitative mechanistic
      studies on SET in GaN-HEMTs by applying element- and site-specific photoelectron
      nanospectroscopy to a GaN-HEMT device under operation. Our study reveals that SET
      is induced by a large local electric field. Furthermore, surface passivation
      using a SiN thin film is demonstrated to play a dual role: electric-field
      weakening and giving rise to chemical interactions that suppress SET. Our
      findings can contribute to the realization of high-capacity wireless
      communication systems based on GaN-HEMTs.

PMID- 30185803
TI  - Characterization of a lung epithelium specific E-cadherin knock-out model:
      Implications for obstructive lung pathology.
AB  - The airway epithelium regulates responses to aeroallergens, acting as a physical
      and immunological barrier. In asthma, epithelial barrier function and the
      expression of adherens junction protein E-cadherin is compromised, but it is
      unknown whether this is cause or consequence of the disease. We hypothesized that
      airway epithelial loss of E-cadherin is a critical step in the development of
      manifestations of asthma. We generated a transgenic mouse model with conditional
      loss of E-cadherin in lung epithelial cells at birth and onwards. We observed
      normal lung development at the time of birth in mice lacking E-cadherin in the
      lung epithelium. However, E-cadherin deficiency led to progressive epithelial
      damage in mice growing into adulthood, as evidenced by airway epithelial
      denudation, decreased zonula occludens (ZO)-1 expression, loss of ciliated cells,
      and enlarged alveolar spaces. In addition, spontaneous goblet cell metaplasia
      with mucus production was observed. These epithelial changes were accompanied by
      elevated levels of the epithelial-derived chemokine CCL17, infiltration of
      eosinophils and dendritic cells, and mucus production. In conclusion, loss of E
      cadherin induces features in the lung reminiscent of those observed in asthma,
      indicating that the disruption of E-cadherin-mediated cell-cell contacts may play
      a key role in the development of asthma manifestations.

PMID- 30185805
TI  - Stage-specific epigenetic regulation of CD4 expression by coordinated enhancer
      elements during T cell development.
AB  - The inheritance of gene expression patterns is dependent on epigenetic
      regulation, but the establishment and maintenance of epigenetic landscapes during
      T cell differentiation are incompletely understood. Here we show that two stage
      specific Cd4 cis-elements, the previously characterized enhancer E4p and a novel
      enhancer E4m, coordinately promote Cd4 transcription in mature thymic MHC-II
      specific T cells, in part through the canonical Wnt pathway. Specifically, E4p
      licenses E4m to orchestrate DNA demethylation by TET1 and TET3, which in turn
      poises the Cd4 locus for transcription in peripheral T cells. Cd4 locus
      demethylation is important for subsequent Cd4 transcription in activated
      peripheral T cells wherein these cis-elements become dispensable. By contrast, in
      developing thymocytes the loss of TET1/3 does not affect Cd4 transcription,
      highlighting an uncoupled event between transcription and epigenetic
      modifications. Together our findings reveal an important function for thymic cis
      elements in governing gene expression in the periphery via a heritable epigenetic
      mechanism.

PMID- 30185807
TI  - Publisher Correction: Strongly-coupled quantum critical point in an all-in-all
      out antiferromagnet.
AB  - The original PDF version of the Article contained an error in the last sentence
      of the author affiliation information, which incorrectly read 'Correspondence and
      requests for materials should be addressed to T.$.R. (e-mail: tfr@caltech.edu) or
      to Y.F. (e-mail: yejun@oist.jp)'. The correct version states 'T.F.R.' in place of
      "T.$.R.'. This has been corrected in the PDF version of the Article. The HTML
      version was correct from the time of publication.

PMID- 30185806
TI  - Machine learning identified an Alzheimer's disease-related FDG-PET pattern which
      is also expressed in Lewy body dementia and Parkinson's disease dementia.
AB  - Utilizing the publicly available neuroimaging database enabled by Alzheimer's
      disease Neuroimaging Initiative (ADNI; http://adni.loni.usc.edu/ ), we have
      compared the performance of automated classification algorithms that
      differentiate AD vs. normal subjects using Positron Emission Tomography (PET)
      with fluorodeoxyglucose (FDG). General linear model, scaled subprofile modeling
      and support vector machines were examined. Among the tested classification
      methods, support vector machine with Iterative Single Data Algorithm produced the
      best performance, i.e., sensitivity (0.84) * specificity (0.95), by 10-fold cross
      validation. We have applied the same classification algorithm to four different
      datasets from ADNI, Health Science Centre (Winnipeg, Canada), Dong-A University
      Hospital (Busan, S. Korea) and Asan Medical Centre (Seoul, S. Korea). Our data
      analyses confirmed that the support vector machine with Iterative Single Data
      Algorithm showed the best performance in prediction of future development of AD
      from the prodromal stage (mild cognitive impairment), and that it was also
      sensitive to other types of dementia such as Parkinson's Disease Dementia and
      Dementia with Lewy Bodies, and that perfusion imaging using single photon
      emission computed tomography may achieve a similar accuracy to that of FDG-PET.

PMID- 30185808
TI  - Sphingosine Kinases promote IL-17 expression in human T lymphocytes.
AB  - Sphingosine 1-phosphate (S1P) has a role in many cellular processes. S1P is
      involved in cell growth and apoptosis, regulation of cell trafficking, production
      of cytokines and chemokines. The kinases SphK1 and SphK2 (SphKs) phosphorilate
      Sphingosine (Sph) to S1P and several phosphatases revert S1P to sphingosine, thus
      assuring a balanced pool that can be depleted by a Sphingosine lyase in
      hexadecenal compounds and aldehydes. There are evidences that SphK1 and 2 may per
      se control cellular processes. Here, we report that Sph kinases regulate IL-17
      expression in human T cells. SphKs inhibition impairs the production of IL-17,
      while their overexpression up-regulates expression of the cytokine through
      acetylation of IL-17 promoter. SphKs were up-regulated also in PBMCs of patients
      affected by IL-17 related diseases. Thus, S1P/S1P kinases axis is a mechanism
      likely to promote IL-17 expression in human T cells, representing a possible
      therapeutic target in human inflammatory diseases.

PMID- 30185809
TI  - Pixelated Metasurface for Dual-Band and Multi-Polarization Electromagnetic Energy
      Harvesting.
AB  - A dual-band and polarization-independent electromagnetic energy harvester
      composed of an array of pixelated unit cells is proposed. The pixelated unit cell
      is basically a dual-band resonator loaded with two resistors which model the
      input impedance of a power combining circuit in a complete harvesting system. To
      design the unit cell, a topology optimization approach based on pixelization of
      the surface of the unit cell and application of a binary optimization algorithm
      is used. The optimization goal is set to maximize harvesting efficiency at 2.45
      GHz and 6 GHz. In our design, full symmetry of the unit cell is considered to
      achieve insensitivity to the polarization of the incident wave. Once, the unit
      cell is designed, as a proof of the concept, a metasurface harvester composed of
      9 * 9 pixelated cells is designed. The full-wave electromagnetic simulation
      results demonstrate that the proposed metasurface absorbs the incident
      electromagnetic wave energy with nearly unity efficiency at both frequencies of
      interest and irrespective the polarization of the incident field while
      simultaneously delivering the absorbed power to the loads. To validate the
      simulations, the metasurface harvester is fabricated and tested in an anechoic
      chamber. A strong agreement between the simulation results and measurements is
      observed.

PMID- 30185810
TI  - The DNMT3A R882H mutation does not cause dominant negative effects in purified
      mixed DNMT3A/R882H complexes.
AB  - The DNA methyltransferase DNMT3A R882H mutation is observed in 25% of all AML
      patients. DNMT3A is active as tetramer and the R882H mutation is located in one
      of the subunit/subunit interfaces. Previous work has reported that formation of
      mixed wildtype/R882H complexes leads to a strong loss of catalytic activity
      observed in in vitro DNA methylation assays (Russler-Germain et al., 2014, Cancer
      Cell 25:442-454). To investigate this effect further, we have prepared mixed
      wildtype/R882H DNMT3A complexes by incubation of individually purified subunits
      of the DNMT3A catalytic domain and full-length DNMT3A2. In addition, we have used
      a double affinity tag approach and specifically purified mixed catalytic domain
      complexes formed after co-expression of R882H and wildtype subunits in E. coli
      cells. Afterwards, we determined the catalytic activity of the mixed complexes
      and compared it to that of purified complexes only consisting of one subunit
      type. In both settings, the expected catalytic activities of mixed R882H/wildtype
      complexes were observed demonstrating an absence of a dominant negative effect of
      the R882H mutation in purified DNMT3A enzymes. This result suggests that
      heterocomplex formation of DNMT3A and R882H is unlikely to cause dominant
      negative effects in human cells as well. The limitations of this conclusion and
      its implications are discussed.

PMID- 30185811
TI  - A holistic approach to the age validation of Mullus barbatus L., 1758 in the
      Southern Adriatic Sea (Central Mediterranean).
AB  - The growth of Mullus barbatus has been widely studied using different methods,
      but no previous study has focused on age validation. The uncertainty in
      estimating the age of the red mullet by otolith reading is linked to the number
      of false-growth increments laid down before the annulus. The capture of red
      mullets in the early life stage allowed us to estimate their size at the
      metamorphosis from the pelagic to the demersal phase. The comparison between the
      metamorphosis size and the back-calculated length of the first growth increment
      clarified the position of the false growth increment on the otolith. Moreover,
      the analyses of the otolith marginal increments in adult and juvenile specimens
      allowed us to define the deposition patterns of their annuli. The modal
      components of the length-frequency distribution analysis (LFDA) were identified
      in the winter survey (ELEFAN and Bhattacharya methods), and they did not show
      significant differences from the length back-calculation of the annuli. Moreover,
      no significant differences were found between the growth curves calculated by
      otolith reading (back-calculation and direct otolith reading) and the LFDA. The
      agreement between the length-frequency results and the otolith age estimation
      either corroborated or indirectly validated the growth pattern estimated in the
      otoliths of the red mullet, mainly when the direct validation methods (e.g. mark
      recapture, captivity, radiochemical) were difficult to implement, like the case
      of this species. The comparison of the results of the present work to previous
      Mediterranean studies showed agreement with the slow growth pattern.

PMID- 30185812
TI  - Ultrastructure and Enzymatic Hydrolysis of Deuterated Switchgrass.
AB  - Neutron scattering of deuterated plants can provide fundamental insight into the
      structure of lignocellulosics in plant cell walls and its deconstruction by
      pretreatment and enzymes. Such plants need to be characterized for any
      alterations to lignocellulosic structure caused by growth in deuterated media.
      Here we show that glucose yields from enzymatic hydrolysis at lower enzyme
      loading were 35% and 30% for untreated deuterated and protiated switchgrass,
      respectively. Lignin content was 4% higher in deuterated switchgrass but there
      were no significant lignin structural differences. Transmission electron
      microscopy showed differences in lignin distribution and packing of fibers in the
      cell walls that apparently increased surface area of cellulose in deuterated
      switchgrass, increasing cellulose accessibility and lowering its recalcitrance.
      These differences in lignification were likely caused by abiotic stress due to
      growth in deuterated media.

PMID- 30185814
TI  - Primary immunodeficiency diseases in a tuberculosis endemic region: challenges
      and opportunities.
AB  - While individual primary immunodeficiency diseases (PIDs) are rare, collectively
      they represent a significant burden of disease. Recent estimates show that about
      one million people in Africa suffer from a PID. However, data from African PID
      registries reflect only a small percentage of the estimated prevalence. This
      disparity is partly due to the lack of PID awareness and the masking of PIDs by
      the endemic pathogens. Over three million tuberculosis (TB) cases were reported
      in Africa in 2016, with many of these from southern Africa. Despite concerted
      efforts to address this high burden of disease, the underlying genetic correlates
      of susceptibility to TB remain poorly understood. High penetrance mutations in
      immune system genes can cause PIDs that selectively predispose individuals to TB
      and other mycobacterial diseases. Additionally, the identification of individuals
      at a heightened risk of developing TB or of presenting with severe or
      disseminated TB due to their genetic ancestry is crucial to promote a positive
      treatment outcome. The screening for and identification of PID mutations in TB
      endemic regions by next-generation sequencing (NGS) represents a promising
      approach to improve the understanding of what constitutes an effective immune
      response to TB, as well as the range of associated PIDs and phenotypes.

PMID- 30185813
TI  - JMJD6 regulates histone H2A.X phosphorylation and promotes autophagy in triple
      negative breast cancer cells via a novel tyrosine kinase activity.
AB  - Overexpression of Jumonji domain-containing 6 (JMJD6) has been reported to be
      associated with more aggressive breast cancer characteristics. However, the
      precise role of JMJD6 in breast cancer development remains unclear. Here, we
      demonstrate that JMJD6 has intrinsic tyrosine kinase activity and can utilize ATP
      and GTP as phosphate donors to phosphorylate Y39 of histone H2A.X (H2A.XY39ph).
      High JMJD6 levels promoted autophagy in triple negative breast cancer (TNBC)
      cells by regulating the expression of autophagy-related genes. The JMJD6
      H2A.XY39ph axis promoted TNBC cell growth via the autophagy pathway. We show that
      combined inhibition of JMJD6 kinase activity and autophagy efficiently decreases
      TNBC growth. Together, these findings suggest an effective strategy for TNBC
      treatment.

PMID- 30185815
TI  - Why growth of nutrient-limited micro-organisms should have low-temperature
      sensitivity.

PMID- 30185817
TI  - Characterization of Mutations in the Mitochondrial Encoded Electron Transport
      Chain Complexes in Acute Myeloid Leukemia.
AB  - Acute Myeloid Leukemia is a devastating and heterogeneous, hematological
      malignancy characterized by the uncontrolled proliferation of undifferentiated
      myeloid progenitor cells-blasts. Mutations in certain mitochondrial proteins,
      such as IDH2 have been shown to contribute to leukemogenesis. However, the role
      of mutations in mitochondrial-encoded Electron Transport Chain (ETC) genes have
      thus far not been well elucidated in AML. Here, we use TCGA data to characterize
      mutations in the ETC genes and their association with clinical outcomes in AML.
      We found that mitochondrial ETC mutations-in Complex I, III, IV and/or V (ATP
      Synthase)-were present in 8% of patients with AML and were significantly more
      frequent in older patients. Patients with ETC mutations had worse overall
      survival than ETC wild type patients (OS: 9.3 vs 20.1 months; p-value: 0.007).
      Additionally, mutations in either or both Complex I and IV were associated with
      TP53 mutations (p-value: 0.009), and among TP53 mutated patients, mutations in
      either or both Complex I and IV were significantly associated with worse overall
      survival (OS: 0.85 vs 9.4 months; p-value: 0.008). Elucidation of the mechanisms
      by which ETC mutations contribute to AML pathogenesis and progression would
      facilitate the development of novel therapeutic targets.

PMID- 30185818
TI  - Anomalous twin boundaries in two dimensional materials.
AB  - Twin boundary defects form in virtually all crystalline materials as part of
      their response to applied deformation or thermal stress. For nearly six decades,
      graphite has been used as a textbook example of twinning with illustrations
      showing atomically sharp interfaces between parent and twin. Using state-of-the
      art high-resolution annular dark-field scanning transmission electron microscopy,
      we have captured atomic resolution images of graphitic twin boundaries and find
      that these interfaces are far more complex than previously supposed. Density
      functional theory calculations confirm that the presence of van der Waals bonding
      eliminates the requirement for an atomically sharp interface, resulting in long
      range bending across multiple unit cells. We show these remarkable structures are
      common to other van der Waals materials, leading to extraordinary
      microstructures, Raman-active stacking faults, and sub-surface exfoliation within
      bulk crystals.

PMID- 30185816
TI  - Cerebrospinal fluid concentrations of inflammatory markers in Parkinson's disease
      and atypical parkinsonian disorders.
AB  - Inflammation has been implicated in the pathogenesis of Parkinson's disease (PD).
      We here investigate levels of inflammatory biomarkers in cerebrospinal fluid
      (CSF) in PD and atypical parkinsonian disorders (APD) compared with
      neurologically healthy controls. We included 131 patients with PD and 27 PD with
      dementia (PDD), 24 with multiple system atrophy (MSA), 14 with progressive
      supranuclear palsy (PSP) and 50 controls, all part of the Swedish BioFINDER
      study. CSF was analyzed for CRP, SAA, IL-6, IL-8, YKL-40 and MCP-1 (CCL2) as well
      as alpha-synuclein (alpha-syn), tau, tau phosphorylated at Thr181 (P-tau),
      Abeta42 and NfL. In this exploratory study, we found higher levels of the
      inflammatory biomarker SAA in PDD and MSA compared with controls and PD and
      higher levels of CRP in PDD and MSA compared with PD. YKL-40 was lower in PD
      compared with controls. There were multiple positive correlations between the
      inflammatory markers, alpha-syn and markers of neuroaxonal injury (NfL and tau).
      In PD, higher levels of inflammatory biomarkers correlated with worse motor
      function and cognitive impairment. Thus, inflammatory biomarkers were increased
      in PDD and MSA. Furthermore, inflammatory biomarkers correlated with more severe
      disease regarding motor symptoms and cognitive impairment in PD, indicating an
      association between inflammation and more aggressive disease course. However, the
      results need confirmation in follow-up studies.

PMID- 30185819
TI  - The use of random forests modelling to detect yeast-mannan sensitive bacterial
      changes in the broiler cecum.
AB  - In this study, sequencing of the 16S rRNA gene targeting the V4-V6 regions was
      conducted to assess the cecal microbial alterations in response to dietary
      supplementation with a yeast derived mannan rich fraction (MRF) in standard
      commercial broiler production settings across four separate broiler trials. The
      resulting data was analysed to identify consistent changes in the bacterial
      community structure of the broiler cecum in response to MRF supplementation.
      Subsequently, the datasets from each individual trial were pooled and analysed
      for differences between control and MRF supplemented diets at day 35 posthatch.
      The results from this analysis showed that Phylum Firmicutes was decreased and
      Phylum Bacteroidetes was increased across all four trials at day 35 posthatch
      when compared to the control. An extension of the random forest bioinformatics
      approach to discover a highly relevant set of microbial operational taxonomic
      units (OTUs) which are indicative of MRF supplementation in the broiler cecum was
      then used. This approach has enabled the identification of a novel set of yeast
      mannan sensitive bacterial OTUs in the cecal microbiome. This information will be
      helpful in developing potential future nutritional strategies and will be
      favourable to the poultry industry.

PMID- 30185821
TI  - Agricultural fungicides inadvertently influence the fitness of Colorado potato
      beetles, Leptinotarsa decemlineata, and their susceptibility to insecticides.
AB  - The Colorado potato beetle (CPB), Leptinotarsa decemlineata (Say), is an
      agricultural pest of solanaceous crops which has developed insecticide resistance
      at an alarming rate. Up to this point, little consideration has been given to
      unintended, or inadvertent effects that non-insecticide xenobiotics may have on
      insecticide susceptibility in L. decemlineata. Fungicides, such as chlorothalonil
      and boscalid, are often used to control fungal pathogens in potato fields and are
      applied at regular intervals when L. decemlineata populations are present in the
      crop. In order to determine whether fungicide use may be associated with elevated
      levels of insecticide resistance in L. decemlineata, we examined phenotypic
      responses in L. decemlineata to the fungicides chlorothalonil and boscalid. Using
      enzymatic and transcript abundance investigations, we also examined modes of
      molecular detoxification in response to both insecticide (imidacloprid) and
      fungicide (boscalid and chlorothalonil) application to more specifically
      determine if fungicides and insecticides induce similar metabolic detoxification
      mechanisms. Both chlorothalonil and boscalid exposure induced a phenotypic,
      enzymatic and transcript response in L. decemlineata which correlates with known
      mechanisms of insecticide resistance.

PMID- 30185820
TI  - Improvement of osteogenesis by a uniform PCL coating on a magnesium screw for
      biodegradable applications.
AB  - A polymer coating as polycaprolactone (PCL) is applied to improve the initial
      corrosion resistance of biodegradable magnesium. In addition, plasma electrolytic
      oxidation (PEO) is performed to increase adhesion between the polymer and the
      metal. However, when a complex-shaped material such as a screw is implanted in a
      bone, the surface coatings are locally damaged, and the protective role of the
      coating is not sufficiently maintained. In this study, the optimal conditions for
      producing a polymer coating on a screw were determined by varying the
      concentration of the PCL and the coating cycles, and were examined in vitro and
      in vivo. Among various the PCL coating conditions of 2~6 cycles with 5~7 wt.%
      concentrations, the 6 wt.% + 4 cycles group was applied uniformly to the screw
      thread. In the case of the non-uniform PCL layers, oxides and gases were present
      between the Mg and the PCL layer because internal magnesium corrosion and the
      layer peel off. The 6 wt.% + 4 cycles group had a high corrosion resistance due
      to the low wear on the thread. Denser and thicker bone formed around the PCL
      coated screw in rat femur. This difference was due to the high corrosion
      resistance, which provided sufficient time for bone healing and promoting new
      bone growth.

PMID- 30185822
TI  - Structural Analysis of Redox-sensing Transcriptional Repressor Rex from
      Thermotoga maritima.
AB  - The cellular redox state of organisms continues to fluctuate during the
      metabolism. All organisms have various sensors that help detect and adapt to
      changes in the redox state. Nicotinamide adenine dinucleotides (NAD+/NADH), which
      are involved in various cellular metabolic activities as cofactors, have been
      revealed as the key molecules sensing the intra-cellular redox state. The Rex
      family members are well conserved transcriptional repressors that regulate the
      expression of respiratory genes by sensing the redox state according to the intra
      cellular NAD+/NADH balance. Herein, we reported crystal structures of apo and
      NAD+- and NADH-bound forms of Rex from Thermotoga maritima to analyse the
      structural basis of transcriptional regulation depending on either NAD+ or NADH
      binding. The different orientation of the reduced nicotinamide group to helix
      alpha9 caused the rearrangement of N-terminal DNA binding domain, thus resulting
      in closed form of Rex to dissociate from cognate DNA. The structural data of Rex
      from T. maritima also support the previous redox-sensing mechanism models of Rex
      homologues.

PMID- 30185823
TI  - Correction to: CCN2 inhibits lung cancer metastasis through promoting DAPK
      dependent anoikis and inducing EGFR degradation.
AB  - Following publication of their article "CCN2 inhibits lung cancer metastasis
      through promoting DAPK-dependent anoikis and inducing EGFR degradation", the
      authors reported an error in Fig.6b. alpha-Tubulin image of rCCN2 treatment 
      (upper panel in CL1-5) only showed eight lanes, when there should be nine.

PMID- 30185824
TI  - RIPK1 prevents TRADD-driven, but TNFR1 independent, apoptosis during development.
AB  - RIPK1 is an essential downstream component of many pattern recognition and death
      receptors. RIPK1 can promote the activation of caspase-8 induced apoptosis and
      RIPK3-MLKL-mediated necroptosis, however, during development RIPK1 limits both
      forms of cell death. Accordingly, Ripk1-/- mice present with systemic cell death
      and consequent multi-organ inflammation, which is driven through the activation
      of both FADD-caspase-8 and RIPK3-MLKL signaling pathways causing perinatal
      lethality. TRADD is a death domain (DD) containing molecule that mediates
      signaling downstream of TNFR1 and the TLRs. Following the disassembly of the
      upstream receptor complexes either RIPK1 or TRADD can form a complex with FADD
      caspase-8-cFLIP, via DD-DD interactions with FADD, facilitating the activation of
      caspase-8. We show that genetic deletion of Ripk1 licenses TRADD to complex with
      FADD-caspase-8 and activates caspase-8 during development. Deletion of Tradd
      provided no survival advantage to Ripk1-/- animals and yet was sufficient to
      reduce the systemic cell death and inflammation, rescue the intestinal and thymic
      histopathologies, reduce cleaved caspases in most tissues and rescue the anemia
      observed in Ripk1-/- neonates. Furthermore, deletion of Ripk3 is sufficient to
      rescue the neonatal lethality of Ripk1-/-Tradd-/- animals and delays but does not
      completely prevent early mortality. Although Ripk3 deletion provides a
      significant survival advantage, Ripk1-/-Tradd-/-Ripk3-/- animals die between 22
      and 49 days, are runty compared to littermate controls and present with
      splenomegaly. These findings reveal a new mechanism by which RIPK1 limits
      apoptosis through blocking TRADD recruitment to FADD and preventing aberrant
      activation of caspase-8.

PMID- 30185825
TI  - BH3-only proteins are dispensable for apoptosis induced by pharmacological
      inhibition of both MCL-1 and BCL-XL.
AB  - The impressive selectivity and efficacy of BH3 mimetics for treating cancer has
      largely been limited to BCL-2 dependent hematological malignancies. Most solid
      tumors depend on other anti-apoptotic proteins, including MCL-1, for survival.
      The recent description of S63845 as the first specific and potent MCL-1 inhibitor
      represents an important therapeutic advance, since MCL-1 is not targeted by the
      currently available BH3 mimetics, Navitoclax or Venetoclax, and is commonly
      associated with chemoresistance. In this study, we confirm a high binding
      affinity and selectivity of S63845 to induce apoptosis in MCL-1-dependent cancer
      cell lines. Furthermore, S63845 synergizes with other BH3 mimetics to induce
      apoptosis in cell lines derived from both hematological and solid tumors.
      Although the anti-apoptotic BCL-2 family members in these cell lines interact
      with a spectrum of pro-apoptotic BH3-only proteins to regulate apoptosis, these
      interactions alone do not explain the relative sensitivities of these cell lines
      to BH3 mimetic-induced apoptosis. These findings necessitated further
      investigation into the requirement of BH3-only proteins in BH3 mimetic-mediated
      apoptosis. Concurrent inhibition of BCL-XL and MCL-1 by BH3 mimetics in
      colorectal HCT116 cells induced apoptosis in a BAX- but not BAK-dependent manner.
      Remarkably this apoptosis was independent of all known BH3-only proteins.
      Although BH3-only proteins were required for apoptosis induced as a result of BCL
      XL inhibition, this requirement was overcome when both BCL-XL and MCL-1 were
      inhibited, implicating distinct mechanisms by which different anti-apoptotic BCL
      2 family members may regulate apoptosis in cancer.

PMID- 30185826
TI  - Topology of active, membrane-embedded Bax in the context of a toroidal pore.
AB  - Bax is a Bcl-2 protein critical for apoptosis induction. In healthy cells, Bax is
      mostly a monomeric, cytosolic protein, while upon apoptosis initiation it inserts
      into the outer mitochondrial membrane, oligomerizes, and forms pores that release
      proapoptotic factors like Cytochrome c into the cytosol. The structures of active
      Bax and its homolog Bak are only partially understood and the topology of the
      proteins with respect to the membrane bilayer is controversially described in the
      literature. Here, we systematically review and examine the protein-membrane,
      protein-water, and protein-protein contacts of the nine helices of active Bax and
      Bak, and add a new set of topology data obtained by fluorescence and EPR methods.
      We conclude based on the consistent part of the datasets that the
      core/dimerization domain of Bax (Bak) is water exposed with only helices 4 and 5
      in membrane contact, whereas the piercing/latch domain is in peripheral membrane
      contact, with helix 9 being transmembrane. Among the available structural models,
      those considering the dimerization/core domain at the rim of a toroidal pore are
      the most plausible to describe the active state of the proteins, although the
      structural flexibility of the piercing/latch domain does not allow unambiguous
      discrimination between the existing models.

PMID- 30185827
TI  - RAS at the Golgi antagonizes malignant transformation through PTPRkappa-mediated
      inhibition of ERK activation.
AB  - RAS GTPases are frequently mutated in human cancer. H- and NRAS isoforms are
      distributed over both plasma-membrane and endomembranes, including the Golgi
      complex, but how this organizational context contributes to cellular
      transformation is unknown. Here we show that RAS at the Golgi is selectively
      activated by apoptogenic stimuli and antagonizes cell survival by suppressing ERK
      activity through the induction of PTPRkappa, which targets CRAF for
      dephosphorylation. Consistently, in contrast to what occurs at the plasma
      membrane, RAS at the Golgi cannot induce melanoma in zebrafish. Inactivation of
      PTPRkappa, which occurs frequently in human melanoma, often coincident with TP53
      inactivation, accelerates RAS-ERK pathway-driven melanomagenesis in zebrafish.
      Likewise, tp53 disruption in zebrafish facilitates oncogenesis driven by RAS from
      the Golgi complex. Thus, RAS oncogenic potential is strictly dependent on its
      sublocalization, with Golgi complex-located RAS antagonizing tumor development.

PMID- 30185828
TI  - Author Correction: Major ocular trauma in Taiwan: 2002-2004 versus 2012-2014.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has not been fixed in the paper.

PMID- 30185829
TI  - Expression profiling of ubiquitin-related genes in LKB1 mutant lung
      adenocarcinoma.
AB  - Liver kinase B1 (LKB1) is a tumor suppressor, and there is a very high proportion
      of LKB1 mutation in lung adenocarcinoma. The function of LKB1 is closely related
      to that of ubiquitin related genes. Our objective is to analyze the changes in
      ubiquitin-related genes in LKB1 mutant lung adenocarcinoma. We searched The
      Cancer Genome Atlas (TCGA) and obtained gene expression profiles from 230 lung
      adenocarcinoma patients, which were then analyzed using R software. Kaplan-Meier
      curves and Cox proportional hazards regression were applied to estimate survival.
      Real-time reverse transcription PCR was used to verify gene expression. Gene
      function was explored by gene set enrichment analysis. There were significantly
      expressed differences in the ubiquitin-related gene SH3RF1 between the LKB1
      mutant and wild-type lung adenocarcinoma patients (p = 9.78013E-05). Patients
      with LKB1 mutation and high expression of SH3RF1 had a better prognosis than the
      low expression group (HR 0.356, 95% CI 0.136-0.929, p = 0.035). SH3RF1 can
      influence cell cycle, apoptosis, DNA replication and the p53 signaling pathway.
      SH3RF1 might have great clinical value act as a diagnostic biomarker and
      indicator to evaluate the prognosis of LKB1 mutant lung adenocarcinoma patients.
      This gene also can become a new treatment target for LKB1 mutant lung
      adenocarcinoma patients.

PMID- 30185831
TI  - Changes in benthic community structure and sediment characteristics after natural
      recolonisation of the seagrass Zostera muelleri.
AB  - Macrofauna are important contributors to estuarine ecosystem services within and
      outside of seagrass beds. Here we documented the natural recolonisation of a
      temperate seagrass (Zostera muelleri) community over 15 years in an urban estuary
      (Waitemata Harbour, North Island, New Zealand). We also investigated the change
      in macrofaunal communities in relation to seagrass cover over time, from
      transition from bare sandflat to seagrass. Colonisation by seagrass was
      associated with an increase in macrofaunal species diversity (from an average of
      32 species per core in 2001 to 46 species per core in 2015) and abundance (from
      482 to 2273 individuals per core), as well as an increase in sediment mud (from
      4.09% to 12.37%) and organic matter content (from 0.90% to 1.41%). The most
      abundant species within both seagrass and adjacent unvegetated sandflat were
      similar, the polychaetes Heteromastus filiformis, Aricidea sp., and Prionospio
      aucklandica, and the amphipod Paracalliope novizealandiae. The difference in
      macrofaunal community structure between seagrass and unvegetated sandflat was
      primarily associated with higher abundance of P. novizealandiae and lower
      abundance of Pseudopolydora sp. in seagrass. A successional effect was observed
      in macrofaunal communities over the 15 years following seagrass expansion,
      primarily associated with an increase in the abundance of Aricidea sp., H.
      filiformis, and P. novizealandiae, and a reduction in the abundance of the
      bivalve Linucula hartvigiana. This study is the first to document long-term
      changes in seagrass and their associated communities during a natural
      recolonisation event, providing insight into timeframes required both for the
      regrowth of a seagrass meadow from initial colonisation of individual patches, as
      well as the trajectories and timeframes of change from a sandflat to a seagrass
      associated macrofaunal community. This research enhances our understanding of how
      changes in seagrass distributions due to seagrass loss or restoration may affect
      macrofaunal community composition and ultimately ecosystem function.

PMID- 30185830
TI  - Genome wide association study identifies novel potential candidate genes for
      bovine milk cholesterol content.
AB  - This study aimed to identify single nucleotide polymorphisms (SNPs) associated
      with milk cholesterol (CHL) content via a genome wide association study (GWAS).
      Milk CHL content was determined by gas chromatography and expressed as mg of CHL
      in 100 g of fat (CHL_fat) or in 100 mg of milk (CHL_milk). GWAS was performed
      with 1,183 cows and 40,196 SNPs using a univariate linear mixed model. Two and 20
      SNPs were significantly associated with CHL_fat and CHL_milk, respectively. The
      important regions for CHL_fat and CHL_milk were at 41.9 Mb on chromosome (BTA) 17
      and 1.6-3.2 Mb on BTA 14, respectively. DGAT1, PTPN1, INSIG1, HEXIM1, SDS, and
      HTR5A genes, also known to be associated with human plasma CHL phenotypes, were
      identified as potential candidate genes for bovine milk CHL. Additional new
      potential candidate genes for milk CHL were RXFP1, FAM198B, TMEM144, CXXC4, MAML2
      and CDH13. Enrichment analyses suggested that identified candidate genes
      participated in cell-cell signaling processes and are key members in tight
      junction, focal adhesion, Notch signaling and glycerolipid metabolism pathways.
      Furthermore, identified transcription factors such as PPARD, LXR, and NOTCH1
      might be important in the regulation of bovine milk CHL content. The expression
      of several positional candidate genes (such as DGAT1, INSIG1 and FAM198B) and
      their correlation with milk CHL content were further confirmed with RNA sequence
      data from mammary gland tissues. This is the first GWAS on bovine milk CHL. The
      identified markers and candidate genes need further validation in a larger cohort
      for use in the selection of cows with desired milk CHL content.

PMID- 30185832
TI  - Longitudinal analysis of serum cytokine profile among patients with tubercular
      multifocal serpiginoid choroiditis: a pilot study.
AB  - PURPOSE: To analyze the serum cytokines profile in patients with tubercular
      multifocal serpiginoid choroiditis (TB MSC) receiving anti-tubercular therapy
      (ATT) and oral corticosteroids. METHODS: In this prospective longitudinal study,
      patients with active TB MSC were included. Serum levels of interferon (IFN)
      gamma, interleukin (IL)-10, and tumor necrosis factor (TNF)-alpha were analyzed
      using bead-based immunoassay. The levels of transforming growth factor (TGF)-beta
      were measured using cytokine bead array. Serial measurement was performed at
      baseline, 1, 3, and 6 weeks after initiation of therapy. Patients developing
      paradoxical worsening (PW) of TB MSC were identified and their serum levels of
      cytokines were compared with those patients who showed healing of lesions.
      Comparison of cytokine levels with baseline values was also performed. RESULTS:
      Twelve patients (three females) were included in the study. Four patients showed
      paradoxical worsening of TB MSC at 3.2 +/- 1 weeks after initiation of therapy.
      Compared to patients who showed healing of lesions, patients with PW showed
      higher baseline IL-10 (not significant; p = 0.28). Among patients developing PW,
      levels of IFN-gamma peaked at 1 week ((p = 0.01) and levels of TNF-alpha peaked
      at 3 weeks (p = 0.02) (coinciding with PW) compared to patients who showed
      healing. There was no significant difference in TGF-beta levels at any time point
      in either group (p > 0.47). CONCLUSIONS: Baseline and serial levels of
      inflammatory serum cytokines may help in predicting the response to ATT and
      corticosteroids in TB MSC. Patients with paradoxical worsening may show rise in
      pro-inflammatory cytokines after initiation of ATT indicating higher bacillary
      load.

PMID- 30185833
TI  - Treatment of primary full-thickness macular hole by intravitreal injection of
      expansile gas.
AB  - OBJECTIVE: To evaluate the efficacy of intravitreal injection (IVI) of expansile
      gas to treat primary full-thickness macular hole (FTMH). METHODS: Prospective
      interventional case series. Twenty-six eyes of 26 patients in Peking Union
      Medical College Hospital with primary FTMH underwent IVI of perfluoropropane
      (C3F8) 0.2 ml, followed by 7-14 days' face-down positioning. The macular hole
      closure rate, post-operative visual acuity, and the incidence of surgical
      complications were observed. The correlation between the patients' age, macular
      hole diameter, pre-operative best-corrected visual acuity (BCVA), status of the
      vitreous, and the macular hole closure rates were analyzed. RESULTS: A total of
      17 cases (65.4%) had hole closure after IVI of C3F8 alone. The closure rate of
      small, medium, and large FTMH was 85.7, 80, and 33.3%, respectively. Pre
      operative OCT examination showed that 10 cases (37%) had vitreomacular traction
      (VMT), and all of them achieved vitreous-macula separation after IVI of the gas.
      The diameters of the hole (P = 0.024) and the status of the vitreous (P = 0.038)
      had a significance difference for hole closure. The mean pre-operative and post
      operative BCVA was 0.84 +/- 0.29 and 0.49 +/- 0.36 (logMAR), respectively (P <
      0.01). One myope with persistent hole developed rhegmatogenous retinal detachment
      (RRD) 2 months after the surgery. Another myope with hole closure developed RRD
      10 months after the surgery. They achieved hole closure and retinal reattachment
      after vitrectomy and scleral buckling, respectively. CONCLUSION: Intravitreal
      injection of C3F8 gas alone was an effective treatment for small-sized and medium
      sized primary FTMH, but further large prospective studies are needed.

PMID- 30185835
TI  - Post-Infectious Functional Gastrointestinal Disorders Among Populations Living in
      Areas of High Enteric Infection Risk: Adding Some Clarity or Further Muddying the
      Waters.
AB  - Post-infectious functional gastrointestinal disorders (FGID) are a relatively
      well-studied phenomenon among individuals who are resident in temperate and
      higher-income regions around the world. Less is known about the risk of FGID
      among residents in tropical and hyperendemic settings where acute gastroenteritis
      risk and exposure is high. This editorial summarizes the primary results from a
      recently published study focusing on this unique clinical scenario and considers
      the interpretation of the data as well as highlights additional research needs.

PMID- 30185834
TI  - Cardiac resynchronization therapy: a comparison among left ventricular bipolar,
      quadripolar and active fixation leads.
AB  - We evaluated the performance of 3 different left ventricular leads (LV) for
      resynchronization therapy: bipolar (BL), quadripolar (QL) and active fixation
      leads (AFL). We enrolled 290 consecutive CRTD candidates implanted with BL (n =
      136) or QL (n = 97) or AFL (n = 57). Over a minimum 10 months follow-up, we
      assessed: (a) composite technical endpoint (TE) (phrenic nerve stimulation at 8
      V@0.4 ms, safety margin between myocardial and phrenic threshold <2V, LV
      dislodgement and failure to achieve the target pacing site), (b) composite
      clinical endpoint (CE) (death, hospitalization for heart failure, heart
      transplantation, lead extraction for infection), (c) reverse remodeling (RR)
      (reduction of end systolic volume >15%). Baseline characteristics of the 3 groups
      were similar. At follow-up the incidence of TE was 36.3%, 14.3% and 19.9% in BL,
      AFL and QL, respectively (p < 0.01). Moreover, the incidence of RR was 56%, 64%
      and 68% in BL, AFL and QL respectively (p = 0.02). There were no significant
      differences in CE (p = 0.380). On a multivariable analysis, "non-BL leads" was
      the single predictor of an improved clinical outcome. QL and AFL are superior to
      conventional BL by enhancing pacing of the target site: AFL through prevention of
      lead dislodgement while QL through improved management of phrenic nerve
      stimulation.

PMID- 30185836
TI  - Cyanoacrylate Hemostasis for Massive Bleeding After Drainage of Pancreatic Fluid
      Collection by Lumen-apposing Metal Stent.

PMID- 30185837
TI  - Association of the IP3R to STIM1 provides a reduced intraluminal calcium
      microenvironment, resulting in enhanced store-operated calcium entry.
AB  - The involvement of inositol trisphosphate receptor (IP3R) in modulating store
      operated calcium entry (SOCE) was established many years ago. Nevertheless, the
      molecular mechanism responsible for this observation has not been elucidated to
      this date. In the present study we show that IP3R associates to STIM1 upon
      depletion of the endoplasmic reticulum (ER) by activation of the inositol
      trisphosphate signaling cascade via G-protein coupled receptors. IP3R-STIM1
      association results in enhanced STIM1 puncta formation and larger Orai-mediated
      whole-cell currents as well as increased calcium influx. Depleting the ER with a
      calcium ATPase inhibitor (thapsigargin, TG) does not induce IP3R-STIM1
      association, indicating that this association requires an active IP3R. The IP3R
      STIM1 association is only observed after IP3R activation, as evidenced by FRET
      experiments and co-immunoprecipitation assays. ER intraluminal calcium
      measurements using Mag-Fluo-4 showed enhanced calcium depletion when IP3R is
      overexpressed. A STIM1-GCaMP fusion protein indicates that STIM1 detects lower
      calcium concentrations near its EF-hand domain when IP3R is overexpressed when
      compared with the fluorescence reported by a GCaMP homogenously distributed in
      the ER lumen (ER-GCaMP). All these data together strongly suggest that activation
      of inositol trisphosphate signaling cascade induces the formation of the IP3R
      STIM1 complex. The activated IP3R provides a reduced intraluminal calcium
      microenvironment near STIM1, resulting in enhanced activation of Orai currents
      and SOCE.

PMID- 30185839
TI  - Protein: what's on in research on clinical nutrition.

PMID- 30185838
TI  - Strongly Coupled Morphological Features of Aortic Aneurysms Drive Intraluminal
      Thrombus.
AB  - Over 75% of abdominal aortic aneurysms harbor an intraluminal thrombus, and
      increasing evidence suggests that biologically active thrombus contributes to the
      natural history of these potentially lethal lesions. Thrombus formation depends
      on the local hemodynamics, which in turn depends on morphological features of the
      aneurysm and near vasculature. We previously presented a hemodynamically
      motivated "thrombus formation potential" that predicts where and when thrombus
      might form. Herein, we combine detailed studies of the three-dimensional
      hemodynamics with methods of sparse grid collocation and interpolation via
      kriging to examine roles of five key morphological features of aneurysms on
      thrombus formation: lesion diameter, axial position, length, curvature, and renal
      artery position. Computational simulations suggest that maximum diameter is a key
      determinant of thrombogenicity, but other morphological features modulate this
      dependence. More distally located lesions tend to have a higher thrombus
      formation potential and shorter lesions tend to have a higher potential than
      longer lesions, given the same aneurysmal dilatation. Finally, movement of
      vortical structures through the infrarenal aorta and lesion can significantly
      affect thrombogenicity. Formation of intraluminal thrombus within an evolving
      abdominal aortic aneurysm thus depends on coupled morphological features, not all
      intuitive, and computational simulations can be useful for predicting
      thrombogenesis.

PMID- 30185840
TI  - Body composition and insulin resistance in children.
AB  - Insulin resistance is a condition of gluco-metabolic sufferance that may hesitate
      in the further development of type 2 diabetes and cardiovascular disease. The
      development of insulin resistance is mostly associated with the accumulation of
      excessive fat in the body. The epidemic impact of obesity in the youngest
      promoted an increase of the prevalence of insulin resistance also in children and
      adolescents. Increased fat accumulation in the peri-visceral area of the abdomen,
      occurring preferably at and after puberty, and in the liver, as non-alcoholic
      fatty liver disease, plays a role in the process. After puberty, males are at
      higher risk than females to develop insulin resistance. Also ethnicity
      contributes to sensitivity of children to develop insulin resistance, where
      Hispanics, South-Asians, and Indians are at higher risk than Whites and Blacks.In
      spite of the research progress in the field, several questions on the
      relationship between body composition and insulin resistance are still
      unanswered. Multiomics approach, combined with nutrition as well as imaging
      techniques might contribute to unravel the role of body composition on insulin
      resistance.

PMID- 30185841
TI  - Nutrition and diabetes in South Asia.

PMID- 30185842
TI  - Prevention of type 2 diabetes-success story that is waiting for next steps.

PMID- 30185843
TI  - Resting energy expenditure and body composition: critical aspects for clinical
      nutrition.

PMID- 30185844
TI  - Energy expenditure-body size associations: molecular coordination.

PMID- 30185846
TI  - Towards appropriate feeding to prevent malnutrition in infants and toddlers.

PMID- 30185845
TI  - Exercise, energy balance and body composition.
AB  - Activity-induced energy expenditure, as determined by the activity pattern
      including exercise, is the most variable component of daily energy expenditure.
      Here, the focus is on effects of exercise training on energy balance and body
      composition in subjects with a sedentary or light-active lifestyle. Then,
      exercise training induces an energy imbalance consistently lower than prescribed
      energy expenditure from exercise. Additionally, individual responses are highly
      variable and decrease in time. Combining the results from 23 exercise training
      studies in normal-weight, overweight, and obese subjects, varying in duration
      from 2 to 64 weeks, showed an average initial energy imbalance of about 2 MJ/day
      with an exponential decline to nearly zero after about 1 year. A compensatory
      increase in energy intake is the most likely explanation for the lower than
      expected effect of exercise on energy balance. Overall, exercise training results
      in a healthier body composition as reflected by a reduction of body fat,
      especially in overweight and obese subjects, with little or no long-term effect
      on body weight.

PMID- 30185847
TI  - Human body composition: yesterday, today, and tomorrow.

PMID- 30185848
TI  - An iron fortification efficacy study in children in Cote d'Ivoire supports the
      suggestion that tissue iron is protected at the expense of erythrocyte iron.

PMID- 30185849
TI  - How we eat determines what we become: opportunities and challenges brought by
      food delivery industry in a changing world in China.
AB  - Rapid economic growth and urbanization have brought notable changes in China.
      This trend had dramatic impacts to food industry and diet-related behaviors,
      which leads to increasing prevalence of overweight and obesity as well as diet
      related non-communicable diseases (NCDs). With a rapid development of internet
      and e-commerce market, another emerging trend that should not be overlooked is
      the change in food shopping habits induced by the popularity of online-to-offline
      (O2O) food delivery service in China. The O2O food market is a booming industry
      in China, the market scale of O2O food industry is increasing with remarkable
      speed. More than 1/5 of total population in China has already became the users of
      O2O food delivery market. Development of this new trend in food environment is
      inevitable. This game-changing trend brings great opportunities to improve food
      accessibility and availability but meanwhile poses inevitable challenges to the
      whole public health system and social environment in China. This paper offers a
      unique perspective of the opportunities and challenges that the new industry
      brings to food environment, health outcomes caused by related behavior change,
      and its broader influence on social environment.

PMID- 30185851
TI  - Breast-feeding as 'personalized nutrition'.

PMID- 30185850
TI  - Classification of obesity targeted personalized dietary weight loss management
      based on carbohydrate tolerance.

PMID- 30185852
TI  - Behaviour, energy balance, obesity and capitalism.

PMID- 30185853
TI  - Cancer-associated malnutrition.

PMID- 30185854
TI  - Iodine nutrition: recent research and unanswered questions.

PMID- 30185855
TI  - Vitamin D: past, present and future perspectives in the prevention of chronic
      diseases.

PMID- 30185856
TI  - Improving health through diet and exercise in children.

PMID- 30185857
TI  - Physiology of exercise and phase angle: another look at BIA.

PMID- 30185859
TI  - Nutrition sensitive agriculture to achieve better nutritional outcomes.

PMID- 30185858
TI  - Estimands: improving inference in randomized controlled trials in clinical
      nutrition in the presence of missing values.
AB  - For randomized controlled trials, the impact of the amount and handling of
      missing data on the interpretation of the treatment effect has been unclear. The
      current use of intention to treat, per protocol, and complete-case analysis has
      shortcomings. The use of estimands may lead to improved estimation of treatment
      effects through more precise characterizations of the fate of treatments after
      dropout or other post-randomization events. A perspective on current and future
      developments with a view toward clinical nutrition is provided.

PMID- 30185860
TI  - Respiration chamber calorimetry and doubly labeled water: two complementary
      aspects of energy expenditure?

PMID- 30185861
TI  - Exercise: an integral and non-negotiable component of a healthy lifestyle.

PMID- 30185862
TI  - Nutritional epidemiology at a crossroad: how to link observations with
      interventions and why?

PMID- 30185863
TI  - Thirty years of EJCN: a time for reflection.

PMID- 30185864
TI  - A view from the "new world".

PMID- 30185865
TI  - 30 years of EJCN.

PMID- 30185866
TI  - Genome-wide generation and genotyping of informative SNPs to scan molecular
      signatures for seed yield in chickpea.
AB  - We discovered 2150 desi and 2199 kabuli accessions-derived SNPs by cultivar-wise
      individual assembling of sequence-reads generated through genotyping-by
      sequencing of 92 chickpea accessions. Subsequent large-scale validation and
      genotyping of these SNPs discovered 619 desi accessions-derived (DAD) SNPs, 531
      kabuli accessions-derived (KAD) SNPs, 884 multiple accessions-derived (MAD) SNPs
      and 1083 two accessions (desi ICC 4958 and kabuli CDC Frontier)-derived (TAD)
      SNPs that were mapped on eight chromosomes. These informative SNPs were annotated
      in coding/non-coding regulatory sequence components of genes. The MAD-SNPs were
      efficient to detect high intra-specific polymorphic potential and wide natural
      allelic diversity level including high-resolution admixed-population genetic
      structure and precise phylogenetic relationship among 291 desi and kabuli
      accessions. This signifies their effectiveness in introgression breeding and
      varietal improvement studies targeting useful agronomic traits of chickpea. Six
      trait-associated genes with SNPs including quantitative trait nucleotides (QTNs)
      in combination explained 27.5% phenotypic variation for seed yield per plant
      (SYP). A pentatricopeptide repeat (PPR) gene with a synonymous-coding SNP/QTN
      significantly associated with SYP trait was found most-promising in chickpea. The
      essential information delineated can be of immense utility in genomics-assisted
      breeding applications to develop high-yielding chickpea cultivars.

PMID- 30185868
TI  - Indirect Reciprocity and the Evolution of Prejudicial Groups.
AB  - Prejudicial attitudes are widely seen between human groups, with significant
      consequences. Actions taken in light of prejudice result in discrimination, and
      can contribute to societal division and hostile behaviours. We define a new class
      of group, the prejudicial group, with membership based on a common prejudicial
      attitude towards the out-group. It is assumed that prejudice acts as a phenotypic
      tag, enabling groups to form and identify themselves on this basis. Using
      computational simulation, we study the evolution of prejudicial groups, where
      members interact through indirect reciprocity. We observe how cooperation and
      prejudice coevolve, with cooperation being directed in-group. We also consider
      the co-evolution of these variables when out-group interaction and global
      learning are immutable, emulating the possible pluralism of a society. Diversity
      through three factors is found to be influential, namely out-group interaction,
      out-group learning and number of sub-populations. Additionally populations with
      greater in-group interaction promote both cooperation and prejudice, while global
      rather than local learning promotes cooperation and reduces prejudice. The
      results also demonstrate that prejudice is not dependent on sophisticated human
      cognition and is easily manifested in simple agents with limited intelligence,
      having potential implications for future autonomous systems and human-machine
      interaction.

PMID- 30185867
TI  - Hierarchy of human IgG recognition within the Staphylococcus aureus immunome.
AB  - Staphylococcus aureus is an opportunistic pathogen that causes a range of serious
      infections associated with significant morbidity, by strains increasingly
      resistant to antibiotics. However, to date all candidate vaccines have failed to
      induce protective immune responses in humans. We need a more comprehensive
      understanding of the antigenic targets important in the context of human
      infection. To investigate infection-associated immune responses, patients were
      sampled at initial presentation and during convalescence from three types of
      clinical infection; skin and soft tissue infection (SSTI), prosthetic joint
      infection (PJI) and pediatric hematogenous osteomyelitis (PHO). Reactivity of
      serum IgG was tested with an array of recombinant proteins, representing over
      2,652 in-vitro-translated open reading frames (ORFs) from a community-acquired
      methicillin-resistant S. aureus USA300 strain. High-level reactivity was
      demonstrated for 104 proteins with serum IgG in all patient samples. Overall,
      high-level IgG-reactivity was most commonly directed against a subset of secreted
      proteins. Although based on limited surveys, we found subsets of S. aureus
      proteins with differential reactivity with serum samples from patients with
      different clinical syndromes. Together, our studies have revealed a hierarchy
      within the diverse proteins of the S. aureus "immunome", which will help to
      advance efforts to develop protective immunotherapeutic agents.

PMID- 30185869
TI  - Lysyl oxidase (LOX) limits VSMC proliferation and neointimal thickening through
      its extracellular enzymatic activity.
AB  - Lysyl oxidase (LOX) plays a critical role in extracellular matrix maturation and
      limits VSMC proliferation and vascular remodeling. We have investigated whether
      this anti-proliferative effect relies on the extracellular catalytically active
      LOX or on its biologically active propeptide (LOX-PP). High expression levels of
      both LOX and LOX-PP were detected in the vascular wall from transgenic mice over
      expressing the full-length human LOX cDNA under the control of SM22alpha promoter
      (TgLOX), which targets the transgene to VSMC without affecting the expression of
      mouse LOX isoenzymes. TgLOX VSMC also secrete high amounts of both mature LOX and
      LOX-PP. Wild-type (WT) mouse VSMC exposed to VSMC supernatants from transgenic
      animals showed reduced proliferative rates (low [3H]-thymidine uptake and
      expression of PCNA) than those incubated with conditioned media from WT cells,
      effect that was abrogated by beta-aminopropionitrile (BAPN), an inhibitor of LOX
      activity. Lentiviral over-expression of LOX, but not LOX-PP, decreased human VSMC
      proliferation, effect that was also prevented by BAPN. LOX transgenesis neither
      impacted local nor systemic inflammatory response induced by carotid artery
      ligation. Interestingly, in this model, BAPN normalized the reduced neointimal
      thickening observed in TgLOX mice. Therefore, extracellular enzymatically active
      LOX is required to limit both VSMC proliferation and vascular remodeling.

PMID- 30185870
TI  - Metabolome and molecular basis for carbohydrate increase and nitrate reduction in
      burley tobacco seedlings by glycerol through upregulating carbon and nitrogen
      metabolism.
AB  - Burley tobacco (Nicotiana Tabacum) is a chlorophyll-deficiency mutant. Nitrate is
      one precursor of tobacco-specific nitrosamines (TSNAs) and is largely accumulated
      in burley tobacco. To decrease nitrate accumulation in burley tobacco, glycerol,
      a polyhydric alcohol compound and physiological regulating material, was sprayed
      and its effects were investigated based on metabolomic technology and molecular
      biology. The results showed that glucose, glutamine and glutamic acid increased
      by 2.6, 5.1 and 196, folds, respectively, in tobacco leaves after glycerol
      application. Nitrate content was significantly decreased by 12-16% and expression
      of eight genes responsible for carbon and nitrogen metabolism were up-regulated
      with glycerol applications under both normal and 20% reduced nitrogen levels (P <
      0.01). Leaf biomass of plants sprayed with glycerol and 20% nitrogen reduction
      was equivalent to that of no glycerol control with normal nitrogen application.
      Carbohydrates biosynthesis, nitrate transport and nitrate assimilation were
      enhanced in glycerol sprayed burley tobacco seedlings which might contribute to
      reduced nitrate and increased carbohydrates contents. In conclusion, glyerol
      spray coupled with 20% nitrogen reduction would be an effective method to reduce
      nitrate accumulation in burley tobacco.

PMID- 30185871
TI  - Buried remnants of the Laurentide Ice Sheet and connections to its surface
      elevation.
AB  - The Laurentide Ice Sheet (LIS) occupied a large part of North-America during the
      late Pleistocene. Determining the proper surface geometry and elevation of the
      LIS is of central importance to estimate global changes in sea-level and
      atmospheric circulation patterns during the late Pleistocene and Holocene.
      Despite largely disappearing from the landscape during the late Holocene, LIS
      remnants are found in the Penny and Barnes ice caps on Baffin Island (Canada) and
      ongoing permafrost degradation has been exposing relics of the LIS buried along
      its northern margin since the late Pleistocene. Here, we use the delta18O records
      of six LIS remnants and the late Pleistocene delta18O-elevation relation to
      establish ice elevation in their source area during the last glacial maximum
      (LGM). Contrary to some modeled reconstructions, our findings indicate an
      asymmetric LIS topography with higher ice on Keewatin Dome (~3200 m) and thinner
      ice in the prairies along the Plains divide (1700-2100 m) during LGM. The
      resiliency of icy permafrost to past warm intervals preserved relics of the LIS;
      these ice-marginal landscapes, now poised for thaw, should uncover more valuable
      clues about the conditions of the last major ice sheet on Earth.

PMID- 30185872
TI  - The diverse magneto-optical selection rules in bilayer black phosphorus.
AB  - The magneto-optical properties of bilayer phosphorene is investigated by the
      generalized tight-binding model and the gradient approximation. The vertical
      inter-Landau-level transitions, being sensitive to the polarization directions,
      are mainly determined by the spatial symmetries of sub-envelope functions on the
      distinct sublattices. The anisotropic excitations strongly depend on the electric
      and magnetic fields. A uniform perpendicular electric field could greatly
      diversify the selection rule, frequency, intensity, number and form of symmetric
      absorption peaks. Specifically, the unusual magneto-optical properties appear
      beyond the critical field as a result of two subgroups of Landau levels with the
      main and side modes. The rich and unique magnetoabsorption spectra arise from the
      very close relations among the geometric structures, multiple intralayer and
      interlayer hopping integrals and composite external fields.

PMID- 30185873
TI  - Peptidyl arginine deiminase 2 (Padi2) is expressed in Sertoli cells in a specific
      manner and regulated by SOX9 during testicular development.
AB  - Peptidyl arginine deiminases (PADIs) are enzymes that change the charge of
      proteins through citrullination. We recently found Padi2 was expressed
      exclusively in fetal Sertoli cells. In this study, we analyzed the
      transcriptional regulation of Padi2 and the role of PADI2 in testicular
      development. We showed SOX9 positively regulated Padi2 transcription and FOXL2
      antagonized it in TM3 cells, a model of Sertoli cells. The responsive region to
      SOX9 and FOXL2 was identified within the Padi2 sequence by reporter assay. In
      fetal testes from Sox9 knockout (AMH-Cre:Sox9flox/flox) mice, Padi2 expression
      was greatly reduced, indicating SOX9 regulates Padi2 in vivo. In vitro analysis
      using siRNA suggested PADI2 modified transcriptional regulation by SOX9. However,
      Padi2-/- XY mice were fertile and showed no apparent reproductive anomalies.
      Although, PADI2 is known as an epigenetic transcriptional regulator through H3
      citrullination, no significant difference in H3 citrullination between wildtype
      and Padi2-/- XY gonads was observed. These results suggest Padi2 is a novel gene
      involved in testis development that is specifically expressed in Sertoli cells
      through the regulation by SOX9 and FOXL2 and PADI2 supports regulation of target
      genes by SOX9. Analysis of the Padi2-/- XY phenotype suggested a redundant factor
      compensated for PADI2 function in testicular development.

PMID- 30185874
TI  - E-hooks provide guidance and a soft landing for the microtubule binding domain of
      dynein.
AB  - Macromolecular binding is a complex process that involves sensing and approaching
      the binding partner, adopting the proper orientation, and performing the physical
      binding. We computationally investigated the role of E-hooks, which are
      intrinsically disordered regions (IDRs) at the C-terminus of tubulin, on dynein
      microtubule binding domain (MTBD) binding to the microtubule as a function of the
      distance between the MTBD and its binding site on the microtubule. Our results
      demonstrated that the contacts between E-hooks and the MTBD are dynamical;
      multiple negatively charted patches of amino acids on the E-hooks grab and
      release the same positively charged patches on the MTBD as it approaches the
      microtubule. Even when the distance between the MTBD and the microtubule was
      greater than the E-hook length, the E-hooks sensed and guided MTBD via long-range
      electrostatic interactions in our simulations. Moreover, we found that E-hooks
      exerted electrostatic forces on the MTBD that were distance dependent; the force
      pulls the MTBD toward the microtubule at long distances but opposes binding at
      short distances. This mechanism provides a "soft-landing" for the MTBD as it
      binds to the microtubule. Finally, our analysis of the conformational states of E
      hooks in presence and absence of the MTBD indicates that the binding process is a
      mixture of the induced-fit and lock-and-key macromolecular binding hypotheses.
      Overall, this novel binding mechanism is termed "guided-soft-binding" and could
      have broad-reaching impacts on the understanding of how IDRs dock to structured
      proteins.

PMID- 30185875
TI  - EpCAM homo-oligomerization is not the basis for its role in cell-cell adhesion.
AB  - Cell-surface tumor marker EpCAM plays a key role in proliferation,
      differentiation and adhesion processes in stem and epithelial cells. It is
      established as a cell-cell adhesion molecule, forming intercellular interactions
      through homophilic association. However, the mechanism by which such interactions
      arise has not yet been fully elucidated. Here, we first show that EpCAM monomers
      do not associate into oligomers that would resemble an inter-cellular homo
      oligomer, capable of mediating cell-cell adhesion, by using SAXS, XL-MS and bead
      aggregation assays. Second, we also show that EpCAM forms stable dimers on the
      surface of a cell with pre-formed cell-cell contacts using FLIM-FRET; however, no
      inter-cellular homo-oligomers were detectable. Thus, our study provides clear
      evidence that EpCAM indeed does not function as a homophilic cell adhesion
      molecule and therefore calls for a significant revision of its role in both
      normal and cancerous tissues. In the light of this, we strongly support the
      previously suggested name Epithelial Cell Activating Molecule instead of the
      Epithelial Cell Adhesion Molecule.

PMID- 30185877
TI  - Protective effect of 1950 MHz electromagnetic field in human neuroblastoma cells
      challenged with menadione.
AB  - This study aims to assess whether a 1950 MHz radiofrequency (RF) electromagnetic
      field could protect human neuroblastoma SH-SY5Y cells against a subsequent
      treatment with menadione, a chemical agent inducing DNA damage via reactive
      oxygen species formation. Cells were pre-exposed for 20 h to specific absorption
      rate of either 0.3 or 1.25 W/kg, and 3 h after the end of the exposure, they were
      treated with 10 uM menadione (MD) for 1 h. No differences were observed between
      sham- and RF-exposed samples. A statistically significant reduction in menadione
      induced DNA damage was detected in cells pre-exposed to either 0.3 or 1.25 W/kg
      (P < 0.05). Moreover, our analyses of gene expression revealed that the pre
      exposure to RF almost inhibited the dramatic loss of glutathione peroxidase-based
      antioxidant scavenging efficiency that was induced by MD, and in parallel
      strongly enhanced the gene expression of catalase-based antioxidant protection.
      In addition, RF abolished the MD-dependent down-regulation of oxoguanine DNA
      glycosylase, which is a critical DNA repairing enzyme. Overall, our findings
      suggested that RF pre-exposure reduced menadione-dependent DNA oxidative damage,
      most probably by enhancing antioxidant scavenging efficiency and restoring DNA
      repair capability. Our results provided some insights into the molecular
      mechanisms underlying the RF-induced adaptive response in human neuroblastoma
      cells challenged with menadione.

PMID- 30185879
TI  - Velocity distributions in trapped and mobilized non-wetting phase ganglia in
      porous media.
AB  - Understanding the mobilisation of trapped globules of non-wetting phase during
      two-phase flow has been the aim of numerous studies. However, the driving forces
      for the mobilisation of the trapped phases are still not well understood. Also,
      there is little information about what happens within a globule before, at the
      onset and during mobilization. In this work, we used micro-particle tracking
      velocimetry in a micro-fluidic model in order to visualise the velocity
      distributions inside the trapped phase globules prior and during mobilisation.
      Therefore, time-averaged and instantaneous velocity vectors have been determined
      using fluorescent microscopy. As a porous medium, we used a polydimethylsiloxane
      (PDMS) micro-model with a well-defined pore structure, where drainage and
      imbibition experiments were conducted. Three different geometries of trapped non
      wetting globules, namely droplets, blobs and ganglia were investigated. We
      observed internal circulations inside the trapped phase globules, leading to the
      formation of vortices. The direction of circulating flow within a globule is
      dictated by the drag force exerted on it by the flowing wetting phase. This is
      illustrated by calculating and analyzing the drag force (per unit area) along
      fluid-fluid interfaces. In the case of droplets and blobs, only one vortex is
      formed. The flow field within a ganglion is much more complex and more vortices
      can be formed. The circulation velocities are largest at the fluid-fluid
      interfaces, along which the wetting phase flows and decreases towards the middle
      of the globule. The circulation velocities increased proportionally with the
      increase of wetting phase average velocity (or capillary number). The vortices
      remain stable as long as the globules are trapped, start to change at the onset
      of mobilization and disappear during the movement of globules. They reappear when
      the globules get stranded. Droplets are less prone to mobilization; blobs get
      mobilised in whole; while ganglia may get ruptured and get mobilised only
      partially.

PMID- 30185878
TI  - Histamine causes endothelial barrier disruption via Ca2+-mediated RhoA activation
      and tension at adherens junctions.
AB  - During inflammation, the disruption of the endothelial barrier leads to increased
      microvascular permeability. Whether tension along cell junctions contributes to
      histamine-induced endothelial barrier disruption remains unknown. Rapid Ca2+
      influx induced by both histamine and thrombin was accompanied by endothelial
      barrier breakdown revealed as drop of transendothelial electric resistance in
      primary human microvascular endothelial cells. Interestingly, GLISA measurements
      revealed activation of RhoA but not inactivation of Rac1 at the time-point of
      barrier breakdown. FRET measurements showed activation of RhoA at intercellular
      junctions after both thrombin and histamine exposure. Breakdown coincided with
      increased stress fiber formation but not with translocation of vinculin, which
      was located along junctions in the resting state similar to postcapillary venules
      ex vivo. Moreover, increased tension at AJs was indicated by immunostaining with
      a conformation-sensitive antibody targeting the alpha18-subunit of alpha-catenin.
      Ca2+ chelation by BAPTA-AM and ROCK1 inhibition by Y27632 abolished both increase
      of tension along AJs as well as barrier dysfunction. Moreover, BAPTA-AM decreased
      RhoA activation following histamine stimulation, indicating a key role of Ca2+
      signaling in barrier breakdown. Taken together, in response to histamine, Ca2+
      via RhoA/ROCK activation along endothelial adherens junctions (AJs) appears to be
      critical for barrier disruption and presumably correlated with enhanced tension.
      However, vinculin appears not to be critical in this process.

PMID- 30185876
TI  - Rapid coupling between gravitational forces and the transcriptome in human
      myelomonocytic U937 cells.
AB  - The gravitational force has been constant throughout Earth's evolutionary
      history. Since the cell nucleus is subjected to permanent forces induced by
      Earth's gravity, we addressed the question, if gene expression homeostasis is
      constantly shaped by the gravitational force on Earth. We therefore investigated
      the transcriptome in force-free conditions of microgravity, determined the time
      frame of initial gravitational force-transduction to the transcriptome and
      assessed the role of cation channels. We combined a parabolic flight experiment
      campaign with a suborbital ballistic rocket experiment employing the human
      myelomonocytic cell line U937 and analyzed the whole gene transcription by
      microarray, using rigorous controls for exclusion of effects not related to
      gravitational force and cross-validation through two fully independent research
      campaigns. Experiments with the wide range ion channel inhibitor SKF-96365 in
      combination with whole transcriptome analysis were conducted to study the
      functional role of ion channels in the transduction of gravitational forces at an
      integrative level. We detected profound alterations in the transcriptome already
      after 20 s of microgravity or hypergravity. In microgravity, 99.43% of all
      initially altered transcripts adapted after 5 min. In hypergravity, 98.93% of all
      initially altered transcripts adapted after 75 s. Only 2.4% of all microgravity
      regulated transcripts were sensitive to the cation channel inhibitor SKF-96365.
      Inter-platform comparison of differentially regulated transcripts revealed 57
      annotated gravity-sensitive transcripts. We assume that gravitational forces are
      rapidly and constantly transduced into the nucleus as omnipresent condition for
      nuclear and chromatin structure as well as homeostasis of gene expression.

PMID- 30185880
TI  - Levels of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in raw wastewater
      as an innovative perspective for investigating population-wide exposure to third
      hand smoke.
AB  - Tobacco smoking is the major cause of many chronic diseases, especially lung
      cancer. Knowledge about population-wide tobacco use and exposure is essential to
      characterise its burden on public health and evaluate policy efficacy. Obtaining
      such knowledge remains challenging with current methods (e.g., surveys,
      biomonitoring) but can be achievable with wastewater analysis, a promising tool
      of retrieving epidemiology information. This study examined population-wide
      exposure to tobacco toxicants and carcinogens through wastewater analysis and
      explored relationships among these chemicals. Cotinine, trans-3'-hydroxycotinine,
      anabasine, anatabine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)
      were analysed in samples from Greece, Switzerland and Belgium, where tobacco
      control policies are different. Measured per-capita mass loads were ranked as:
      nicotine biomarkers ? tobacco markers > carcinogens. Relationships between
      nicotine biomarkers and tobacco markers implied substantial use of non-tobacco
      nicotine items besides tobacco products. Geographic profiles of tobacco markers
      revealed higher levels in Geneva and Athens than Geraardsbergen and Ninove.
      Environmental third-hand smoke led to NNK detection, with elevated levels
      observed in Athens where indoor smoking is widespread, posing potential health
      risks to the population. Our novel outcomes are relevant for public health
      authorities as they provide indications about external exposure and can thus be
      used to plan and evaluate tobacco control policies.

PMID- 30185881
TI  - Insight from Molecular dynamic simulation of reactive oxygen species in oxidized
      skin membrane.
AB  - Non-enzymatic lipid peroxidation of the skin-lipid bilayer causes perturbations
      that affect the biomembrane structure, function, and permeability of reactive
      oxygen species (ROS). In the present study, we employed molecular dynamics
      simulations to study the effect of lipid peroxidation on the bilayer structural
      properties and permeability of various ROS. The oxidized skin-lipid bilayer was
      composed of ceramide, cholesterol, free fatty acid, and 5alpha
      hydroperoxycholesterol (5alpha-CH). The simulation showed that, upon oxidation,
      the oxidized group (-OOH) of 5alpha-CH migrates towards the aqueous phase and the
      backbone of 5alpha-CH tilts, which causes the membrane to expand laterally.
      Measurements of the permeability of all ROS along the oxidized skin-lipid bilayer
      revealed a decreased breaching barrier for all the species as the degree of
      peroxidation increased, with a resulting easy passage across the membrane. The
      insights from the simulations indicate that lipid peroxidation might perturb the
      membrane barrier, thereby inflicting oxidative stress that leads to apoptosis.
      This study helps to understand oxidative stress at the atomic level. To our
      knowledge, this is the first reported molecular dynamics simulation study on
      oxidized skin-lipid bilayer and permeability of ROS.

PMID- 30185883
TI  - Small-scale displacement fluctuations of vesicles in fibroblasts.
AB  - The intracellular environment is a dynamic space filled with various organelles
      moving in all directions. Included in this diverse group of organelles are
      vesicles, which are involved in transport of molecular cargo throughout the cell.
      Vesicles move in either a directed or non-directed fashion, often depending on
      interactions with cytoskeletal proteins such as microtubules, actin filaments,
      and molecular motors. How these proteins affect the local fluctuations of
      vesicles in the cytoplasm is not clear since they have the potential to both
      facilitate and impede movement. Here we show that vesicle mobility is
      significantly affected by myosin-II, even though it is not a cargo transport
      motor. We find that myosin-II activity increases the effective diffusivity of
      vesicles and its inhibition facilitates longer states of non-directed motion. Our
      study suggests that altering myosin-II activity in the cytoplasm of cells can
      modulate the mobility of vesicles, providing a possible mechanism for cells to
      dynamically tune the cytoplasmic environment in space and time.

PMID- 30185884
TI  - Detection of high-risk carbapenem-resistant Klebsiella pneumoniae and
      Enterobacter cloacae isolates using volatile molecular profiles.
AB  - Infections caused by carbapenem-resistant Enterobacteriaceae (CRE) are alarming
      in the clinical setting, as CRE isolates often exhibit resistance to most
      clinically-available antibiotics. Klebsiella pneumoniae carbapenemase (KPC) is
      the most common carbapenemase carried by CRE in North America and Europe,
      frequently detected in isolates of K. pneumoniae, Escherichia coli, and
      Enterobacter cloacae. Notably, KPC-expressing strains often arise from clonal
      lineages, with sequence type 258 (ST258) representing the dominant lineage in K.
      pneumoniae, ST131 in E. coli, and ST78 and ST171 in E. cloacae. Prior studies
      have demonstrated that carbapenem-resistant K. pneumoniae differs from carbapenem
      susceptible K. pneumoniae at both the transcriptomic and soluble metabolomic
      levels. In the present study, we sought to determine whether carbapenem-resistant
      and carbapenem-susceptible isolates of K. pneumoniae, E. coli, and E. cloacae
      produce distinct volatile metabolic profiles. We were able to identify a volatile
      metabolic fingerprint that could discriminate between CRE and non-CRE with an
      area under the receiver operating characteristic curve (AUROC) as high as 0.912.
      Species-specific AUROCs were as high as 0.988 for K. pneumoniae and 1.000 for E.
      cloacae. Paradoxically, curing of KPC-expressing plasmids from a subset of K.
      pneumoniae isolates further accentuated the metabolic differences observed
      between ST258 and non-ST258.

PMID- 30185886
TI  - Effects of Geometry on the Electronic Properties of Semiconductor Elliptical
      Quantum Rings.
AB  - The electronic states in GaAs-AlxGa1-xAs elliptically-shaped quantum rings are
      theoretically investigated through the numerical solution of the effective mass
      band equation via the finite element method. The results are obtained for
      different sizes and geometries, including the possibility of a number of hill
      shaped deformations that play the role of either connected or isolated quantum
      dots (hills), depending on the configuration chosen. The quantum ring transversal
      section is assumed to exhibit three different geometrical symmetries - squared,
      triangular and parabolic. The behavior of the allowed confined states as
      functions of the cross-section shape, the ring dimensions, and the number of
      hills-like structures are discussed in detail. The effective energy bandgap
      (photoluminescence peak with electron-hole correlation) is reported as well, as a
      function of the Al molar fraction.

PMID- 30185882
TI  - Genetic Determinants of Telomere Length in African American Youth.
AB  - Telomere length (TL) is associated with numerous disease states and is affected
      by genetic and environmental factors. However, TL has been mostly studied in
      adult populations of European or Asian ancestry. These studies have identified 34
      TL-associated genetic variants recently used as genetic proxies for TL. The
      generalizability of these associations to pediatric populations and racially
      diverse populations, specifically of African ancestry, remains unclear.
      Furthermore, six novel variants associated with TL in a population of European
      children have been identified but not validated. We measured TL from whole blood
      samples of 492 healthy African American youth (children and adolescents between 8
      and 20 years old) and performed the first genome-wide association study of TL in
      this population. We were unable to replicate neither the 34 reported genetic
      associations found in adults nor the six genetic associations found in European
      children. However, we discovered a novel genome-wide significant association
      between TL and rs1483898 on chromosome 14. Our results underscore the importance
      of examining genetic associations with TL in diverse pediatric populations such
      as African Americans.

PMID- 30185885
TI  - MARCKS regulates neuritogenesis and interacts with a CDC42 signaling network.
AB  - Through the process of neuronal differentiation, newly born neurons change from
      simple, spherical cells to complex, sprawling cells with many highly branched
      processes. One of the first stages in this process is neurite initiation, wherein
      cytoskeletal modifications facilitate membrane protrusion and extension from the
      cell body. Hundreds of actin modulators and microtubule-binding proteins are
      known to be involved in this process, but relatively little is known about how
      upstream regulators bring these complex networks together at discrete locations
      to produce neurites. Here, we show that Myristoylated alanine-rich C kinase
      substrate (MARCKS) participates in this process. Marcks-/- cortical neurons
      extend fewer neurites and have less complex neurite arborization patterns. We use
      an in vitro proteomics screen to identify MARCKS interactors in developing
      neurites and characterize an interaction between MARCKS and a CDC42-centered
      network. While the presence of MARCKS does not affect whole brain levels of
      activated or total CDC42, we propose that MARCKS is uniquely positioned to
      regulate CDC42 localization and interactions within specialized cellular
      compartments, such as nascent neurites.

PMID- 30185887
TI  - Liposomes can both enhance or reduce drugs penetration through the skin.
AB  - The adequate formulation of topical vehicles to treat skin diseases is
      particularly complex. A desirable formulation should enhance the accumulation of
      the active drugs in the target tissue (the skin), while avoiding the penetration
      enhancement to be so large that the drugs reach the systemic circulation in toxic
      amounts. We have evaluated the transcutaneous penetration of three drugs chosen
      for their widely variable physicochemical properties: Amphotericin B, Imiquimod
      and Indole. We incorporated the drugs in fluid or ultra-flexible liposomes. Ultra
      flexible liposomes produced enhancement of drug penetration into/through human
      skin in all cases in comparison with fluid liposomes without detergent,
      regardless of drug molecular weight. At the same time, our results indicate that
      liposomes can impede the transcutaneous penetration of molecules, in particular
      small ones.

PMID- 30185889
TI  - Impact of family history of cancer on risk and mortality of second cancers in
      patients with prostate cancer.
AB  - BACKGROUND: Survival rates are increasing in patients with prostate cancer, and
      second primary cancers (SPCs) are becoming more common in these patients.
      However, the etiology and clinical consequences of SPCs are not well-known. We
      define the impact of family history on SPC and causes of mortality in these
      patients. PATIENTS AND METHODS: A nation-wide cohort study based on the Swedish
      Family-Cancer Database covering 4.4 million men and 80,449 prostate cancers
      diagnosed between 1990 and 2015. Relative risks (RRs) and cumulative incidence
      for SPCs and for familial SPC were calculated for prostate cancer patients.
      RESULTS: SPC was diagnosed in 6,396 men and more than a third of these patients
      had a first-degree family history of any cancer; the familial risk was 1.37 (95%
      CI: 1.27-1.40), compared to 1.10 (1.08-1.16), without a family history.
      Cumulative incidence by the age of 83 years reached 21% for prostate cancer
      alone, 28% in those with SPC, and 35% in patients with SPC and family history.
      Family history was associated with the risk of seven specific SPCs, including
      colorectal, lung, kidney, bladder and skin (both melanoma and squamous cell)
      cancers, and leukemia. Colorectal and lung cancers were common SPCs, and family
      history doubled the risk of these SPCs. In patients with SPC, half of all causes
      of death were due to SPC and only 12.77% were due to prostate cancer. Most deaths
      in SPC were caused by lung and colorectal cancers. CONCLUSIONS: SPCs were an
      important cause of death in patients with prostate cancer and family history was
      an important risk factor for SPCs. Prevention of SPC should be essential when
      prostate cancer survival rates are being improved and this could start by
      conducting a thorough assessment of family history at the time of prostate cancer
      diagnosis.

PMID- 30185888
TI  - Interplay between interferon regulatory factor 1 and BRD4 in the regulation of PD
      L1 in pancreatic stellate cells.
AB  - The fibrotic reaction is a characteristic feature of human pancreatic ductal
      adenocarcinoma (PDAC) tumors. It is associated with activation and proliferation
      of pancreatic stellate cells (PSCs), which are key regulators of fibrosis in
      vivo. While there is increasing interest in the regulation of PD-L1 expression in
      cancer and immune cells, the expression and regulation of PD-L1 in other stromal
      cells, such as PSCs, has not been fully evaluated. Here we show that PSCs in
      vitro express higher PD-L1 mRNA and protein levels compared to the levels present
      in PDAC cells. We show that inhibitors targeting bromodomain and extra-terminal
      (BET) proteins and BRD4 knockdown decrease interferon-gamma (IFN-gamma)-induced
      PD-L1 expression in PSCs. We also show that c-MYC, one of the well-established
      targets of BET inhibitors, does not mediate IFN-gamma-regulated PD-L1 expression
      in PSCs. Instead we show that interferon regulatory factor 1 (IRF1) mediates IFN
      gamma-induced PD-L1 expression in PSCs. Finally, while we show that BET
      inhibitors do not regulate IFN-gamma-induced IRF1 expression in PSCs, BET
      inhibitors decrease binding of IRF1 and BRD4 to the PD-L1 promoter. Together,
      these results demonstrate the interplay between IRF1 and BRD4 in the regulation
      of PD-L1 in PSCs.

PMID- 30185890
TI  - A comparison of trunk circumference and width indices for hypertension and type 2
      diabetes in a large-scale screening: a retrospective cross-sectional study.
AB  - Anthropometric indices determine important risk factors for many chronic
      diseases. However, to date, no study has simultaneously analyzed the capabilities
      of trunk circumference and width indices to identify hypertension and type 2
      diabetes in a large-scale screening study. The objectives of this study were to
      examine the associations of hypertension and - diabetes with circumference and
      width indices measured at the five identical positions (axillary, chest, rib,
      waist, and pelvic) and to compare the capabilities of circumference and width
      indices to identify the two diseases. Data were obtained from the Korean Health
      and Genome Epidemiology Study database. The associations and abilities of the
      circumference indices to identify diabetes were greater than those for
      hypertension. Overall, trunk circumference indices displayed stronger
      associations with and greater abilities to identify hypertension and diabetes
      than did trunk width indices at the five positions. In the comparative analysis
      between index pairs of circumference and width in patients with diabetes,
      significant differences were shown at all five positions and in the adjusted
      analysis of axillary, chest, rib, and pelvic positions. Therefore, width indices
      should not be used as an alternative indicator of type 2 diabetes in either men
      or women, except when measured at the waist.

PMID- 30185891
TI  - Discovery of topological nodal-line fermionic phase in a magnetic material
      GdSbTe.
AB  - Topological Dirac semimetals with accidental band touching between conduction and
      valence bands protected by time reversal and inversion symmetry are at the
      frontier of modern condensed matter research. A majority of discovered
      topological semimetals are nonmagnetic and conserve time reversal symmetry. Here
      we report the experimental discovery of an antiferromagnetic topological nodal
      line semimetallic state in GdSbTe using angle-resolved photoemission
      spectroscopy. Our systematic study reveals the detailed electronic structure of
      the paramagnetic state of antiferromagnetic GdSbTe. We observe the presence of
      multiple Fermi surface pockets including a diamond-shape, and small circular
      pockets around the zone center and high symmetry X points of the Brillouin zone
      (BZ), respectively. Furthermore, we observe the presence of a Dirac-like state at
      the X point of the BZ and the effect of magnetism along the nodal-line direction.
      Interestingly, our experimental data show a robust  Dirac-like state both below
      and above the magnetic transition temperature (TN  = 13 K). Having a relatively
      high transition temperature, GdSbTe provides an archetypical platform to study
      the interaction between magnetism and topological states of matter.

PMID- 30185892
TI  - Decreased white matter fractional anisotropy is associated with poorer functional
      motor skills following spinal cord injury: a pilot study.
AB  - STUDY DESIGN: Prospective cross-sectional study OBJECTIVES: The objective of this
      study was to assess associations between white matter changes and functional
      motor markers including grip strength and prehension in the upper limb. SETTING:
      Single Center Imaging Study, in Vancouver Canada. METHODS: Diffusion tensor
      imaging produced FA (Fractional Anisotropy) maps of the brain for participants
      with SCI (n = 7) and controls (n = 6). These FA maps were analyzed using tract
      based spatial statistics. Correlations between the FA values (of the genu of the
      corpus callosum, the left superior longitudinal fasciculus and the right anterior
      thalamic radiation) of the SCI group and functional outcomes (grip strength,
      Graded Redefined Assessment of Strength, Sensibility and Prehension (GRASSP))
      were assessed. RESULTS: Significant differences (p < 0.05) were found between the
      FA values of the controls and the SCI group in two white matter clusters, with
      lower values in the SCI group. Strong correlations were found between the FA
      values of the identified clusters and the age of SCI participant, and the right
      GRASSP Quantitative Prehension and right total GRASSP score. CONCLUSIONS: This
      preliminary data suggests that decreased FA in the genu of the corpus callosum
      may be a biomarker for functional motor ability of the upper limb with higher FA
      indicating better ability. Further research needs to be done to determine if
      other white matter tracts are also associated with strength and use of the hand
      following SCI. SPONSORSHIP: The International Collaboration on Repair Discoveries
      (operating grant) and Canada Research Chair Program (for JJE) provided support
      for this research.

PMID- 30185894
TI  - Effect of the prebiotic fiber inulin on cholesterol metabolism in wildtype mice.
AB  - Dietary non-digestible carbohydrates are perceived to improve health via gut
      microbiota-dependent generation of products such as short-chain fatty acids
      (SCFA). In addition, SCFA are also precursors for lipid and cholesterol synthesis
      potentially resulting in unwanted effects on lipid metabolism. Inulin is a widely
      used model prebiotic dietary fiber. Inconsistent reports on the effects of inulin
      on cholesterol homeostasis have emerged in humans and preclinical models. To
      clarify this issue, the present study aimed to provide an in-depth
      characterization of the effects of short-chain (sc)- and long-chain (lc)- inulin
      on cholesterol synthesis, absorption and elimination in mice. Feeding wildtype
      C57BL/6J mice diets supplemented with 10% (w/w) of either sc- or lc-inulin for
      two weeks resulted in approximately 2.5-fold higher fecal SCFA levels (P < 0.01)
      compared with controls, but had no significant effects on plasma and liver
      lipids. Subtle shifts in fecal and plasma bile acid species were detected with
      beta-muricholic acid increasing significantly in plasma of the inulin fed groups
      (1.7-fold, P < 0.05). However, neither sc-inulin nor lc-inulin affected
      intestinal cholesterol absorption, mass fecal cholesterol excretion or trans
      intestinal cholesterol excretion (TICE). Combined, our data demonstrate that sc-
      and lc-inulin have no adverse effects on cholesterol metabolism in mice despite
      increased generation of SCFA.

PMID- 30185895
TI  - Bright GFP with subnanosecond fluorescence lifetime.
AB  - Fluorescence lifetime imaging microscopy (FLIM) measures fluorescence decay rate
      at every pixel of an image. FLIM can separate probes of the same color but
      different fluorescence lifetimes (FL), thus it is a promising approach for
      multiparameter imaging. However, available GFP-like fluorescent proteins (FP)
      possess a narrow range of FLs (commonly, 2.3-3.5 ns) which limits their
      applicability for multiparameter FLIM. Here we report a new FP probe showing both
      subnanosecond fluorescence lifetime and exceptional fluorescence brightness (80%
      of EGFP). To design this probe we applied semi-rational amino acid substitutions
      selection. Critical positions (Thr65, Tyr145, Phe165) were altered based on
      previously reported effect on FL or excited state electron transfer. The
      resulting EGFP triple mutant, BrUSLEE (Bright Ultimately Short Lifetime Enhanced
      Emitter), allows for both reliable detection of the probe and recording FL signal
      clearly distinguishable from that of the spectrally similar commonly used GFPs.
      We demonstrated high performance of this probe in multiparameter FLIM experiment.
      We suggest that amino acid substitutions described here lead to a significant
      shift in radiative and non-radiative excited state processes equilibrium.

PMID- 30185893
TI  - A systematic review and meta-analysis of prognostic biomarkers in resectable
      esophageal adenocarcinomas.
AB  - Targeted therapy is lagging behind in esophageal adenocarcinoma (EAC). To guide
      the development of new treatment strategies, we provide an overview of the
      prognostic biomarkers in resectable EAC treated with curative intent. The
      Medline, Cochrane and EMBASE databases were systematically searched, focusing on
      overall survival (OS). The quality of the studies was assessed using a scoring
      system ranging from 0-7 points based on modified REMARK criteria. To evaluate all
      identified prognostic biomarkers, the hallmarks of cancer were adapted to fit all
      biomarkers based on their biological function in EAC, resulting in the features
      angiogenesis, cell adhesion and extra-cellular matrix remodeling, cell cycle,
      immune, invasion and metastasis, proliferation, and self-renewal. Pooled hazard
      ratios (HR) and 95% confidence intervals (CI) were derived by random effects meta
      analyses performed on each hallmarks of cancer feature. Of the 3298 unique
      articles identified, 84 were included, with a mean quality of 5.9 points (range
      3.5-7). The hallmarks of cancer feature 'immune' was most significantly
      associated with worse OS (HR 1.88, (95%CI 1.20-2.93)). Of the 82 unique
      prognostic biomarkers identified, meta-analyses showed prominent biomarkers,
      including COX-2, PAK-1, p14ARF, PD-L1, MET, LC3B, IGFBP7 and LGR5, associated to
      each hallmark of cancer.

PMID- 30185897
TI  - Malignant Transformation of Human Bronchial Epithelial Cells Induced by Arsenic
      through STAT3/miR-301a/SMAD4 Loop.
AB  - Arsenic is a well-known of human carcinogen and miR-301a is an oncogenic
      microRNA, which links to oncogenesis, however, little is understood about its
      contribution to arsenic-induced cellular transformation and tumorigenesis. Here,
      we investigated the role of miR-301a during arsenic-induced cellular
      transformation and tumor formation. miR-301a was found to be upregulated during
      arsenic-induced BEAS-2B transformation and the overexpression of miR-301a was
      dependent on IL-6/STAT3 signaling. Inhibition of miR-301a leads to reduction of
      cell proliferation, colony formation and cell migration. By using dual luciferase
      assay, SMAD4 was confirmed to be a direct target of miR-301a in BEAS-2B cells and
      upregulation of SMAD4 is involved the restraining cell growth and migration. In
      addition, reducing of miR-301a expression enhances doxorubicin-induced cellular
      apoptosis of transformed BEAS-2B through up-regulating SMAD4. Furthermore, we
      demonstrated that downregulation of miR-301a in BEAS-2B attenuates tumor growth
      in the xenograft model by targeting SMAD4. Of note, the level of miR-301a
      expression correlated inversely with SMAD4 expression in clinical specimens of
      human lung cancer. Our findings ascertain that miR-301a is an oncogenic miRNA,
      which targets SMAD4 to establish an essential mechanism for arsenic-induced
      carcinogenesis, IL-6/STAT3/miR-301a/SMAD4 signaling pathways.

PMID- 30185898
TI  - HIV infection and increased food insecurity are associated with adverse body
      composition changes among pregnant and lactating Kenyan women.
AB  - BACKGROUND/OBJECTIVES: Body composition changes markedly during reproduction. In
      sub-Saharan Africa, impacts of HIV infection on body composition across pregnancy
      and lactation in the context of Option B+ antiretroviral therapy are unknown.
      Therefore, we sought to evaluate the role of HIV infection on body composition
      during pregnancy and lactation among Kenyan women. SUBJECTS/METHODS: A cohort of
      pregnant women (n = 333; 50.5% HIV+, receiving ART) were enrolled at seven
      clinics in western Kenya. Two prenatal (mean +/- SD: 23.6 +/- 4.4 and 33.4 +/-
      2.0 weeks gestation) and three postpartum (6, 14, and 36 weeks) measurements
      included: individual-level food insecurity, height, weight, fat mass (FM), and
      fat-free mass (FFM) by bioimpedance analysis (BIA), mid-upper arm circumference
      (MUAC), and triceps skinfold (TSF), allowing for AMA (arm muscle area) and AFA
      (arm fat area) derivation. Multivariable longitudinal regression models were used
      to relate HIV to body composition changes. RESULTS: In longitudinal models, HIV
      infected women had lower weight (beta = -3.0 kg, p = 0.003), fat mass (beta = 
      1.5 kg, p = 0.02), fat-free mass (beta = -1.5 kg, p = 0.01), TSF (beta = -2.6 mm,
      p < 0.001), AFA (beta = -3.9 cm3, p < 0.001), and MUAC (beta = -1.0 cm, p =
      0.001), but not AMA (p = 0.34), across all observations. Food insecurity was
      inversely associated with AMA and MUAC postpartum (AMA beta-range = -0.47 to 
      0.92 cm3; MUAC beta-range = -0.09 to -0.15 cm, all p < 0.05). CONCLUSIONS: HIV
      infection was associated with lower weight, fat mass, fat-free mass, TSF, AFA,
      and MUAC values during pregnancy and lactation, while food insecurity was
      intermittently associated with body composition. This suggests that pregnant and
      lactating women living with HIV and food insecurity could benefit from
      nutritional support.

PMID- 30185896
TI  - TiHo-0906: a new feline mammary cancer cell line with molecular, morphological,
      and immunocytological characteristics of epithelial to mesenchymal transition.
AB  - Feline mammary carcinomas (FMCs) with anaplastic and malignant spindle cells
      histologically resemble the human metaplastic breast carcinoma (hMBC), spindle
      cell subtype. hMBCs display epithelial-to-mesenchymal transition (EMT)
      characteristics. Herein we report the establishment and characterization of a
      cell line (TiHoCMglAdcar0906; TiHo-0906) exhibiting EMT-like properties derived
      from an FMC with anaplastic and malignant spindle cells. Copy-number variations
      (CNVs) by next-generation sequencing and immunohistochemical characteristics of
      the cell line and the tumour were compared. The absolute qPCR expression of EMT
      related markers HMGA2 and CD44 was determined. The growth, migration, and
      sensitivity to doxorubicin were assessed. TiHo-0906 CNVs affect several genomic
      regions harbouring known EMT-, breast cancer-, and hMBCs-associated genes as
      AKT1, GATA3, CCND2, CDK4, ZEB1, KRAS, HMGA2, ESRP1, MTDH, YWHAZ, and MYC. Most of
      them were located in amplified regions of feline chromosomes (FCAs) B4 and F2.
      TiHo-0906 cells displayed an epithelial/mesenchymal phenotype, and high HMGA2 and
      CD44 expression. Growth and migration remained comparable during subculturing.
      Low-passaged cells were two-fold more resistant to doxorubicin than high-passaged
      cells (IC50: 99.97 nM, and 41.22 nM, respectively). The TiHo-0906 cell line was
      derived from a poorly differentiated cellular subpopulation of the tumour
      consistently displaying EMT traits. The cell line presents excellent
      opportunities for studying EMT on FMCs.

PMID- 30185899
TI  - Relation between switching time distribution and damping constant in magnetic
      nanostructure.
AB  - It is widely known that the switching time is determined by the thermal stability
      parameters and external perturbations such as magnetic field and/or spin
      polarized current in magnetic nano-structures. Since the thermal stability
      parameter and switching time are crucial values in the design of spin-transfer
      torque magnetic random access memory, the measurement of the switching time is
      important in the study of the switching behavior of ferromagnetic nano
      structures. In this study, we focus on the distribution of the switching time.
      Within the limit of a large energy barrier, a simple analytical expression
      between damping constant and anisotropy field with switching time distribution is
      obtained and confirmed by numerically solving the Fokker-Planck equation. We show
      that the damping constant and anisotropy field can be extracted by measuring the
      full width half maximum of the switching time distribution in the magnetic nano
      structure devices. Furthermore, the present method can be applied to not only
      single nano-structure, but also inhomogeneous nano-structure arrays.

PMID- 30185901
TI  - Dormant Mycobacterium tuberculosis converts isoniazid to the active drug in a
      Wayne's model of dormancy.
AB  - Isoniazid (INH) is one among the four first-line drugs used in the treatment of
      tuberculosis. The bactericidal activity of INH is due to its ability to inhibit
      mycolic acid synthesis, which is an integral component of the mycobacterial cell
      wall. Non-replicating Mycobacterium tuberculosis (MTB) is phenotypically
      resistant to INH. The exact mechanism of this resistance is not clear, although
      the inability of dormant MTB to convert the pro-drug into an active form is
      thought to be one of the possible reasons. Employing targeted metabolomics
      approach, we show that dormant MTB can metabolize INH into its active INH-NAD+
      adduct form. Further we show that the dormant bacteria have unaltered gene
      expression levels of katG and inhA (INH metabolizing enzymes). Transcript levels
      of drug efflux pump proteins which were low during dormancy did not increase in
      response to INH treatment. These findings point to an alternative mechanism for
      INH resistance in dormant MTB, which needs to be further elucidated.

PMID- 30185900
TI  - Barley RNA viromes in six different geographical regions in Korea.
AB  - Barley is a kind of cereal grass belonging to the family Poaceae. To examine
      viruses infecting winter barley in Korea, we carried out a comprehensive study of
      barley RNA viromes using next-generation sequencing (NGS). A total of 110 barley
      leaf samples from 17 geographical locations were collected. NGS followed by
      extensive bioinformatics analyses revealed six different barley viromes: Barley
      yellow mosaic virus (BaYMV), Barley mild mosaic virus (BaMMV), Barley yellow
      dwarf virus (BYDV), Hordeum vulgare endornavirus (HvEV), and Barley virus G
      (BVG). BaYMV and HvEV were identified in all libraries, while other viruses were
      identified in some specific library. Based on the number of virus-associated
      reads, BaYMV was a dominant virus infecting winter barley in Korea causing yellow
      disease symptoms. We obtained nearly complete genomes of six BaYMV isolates and
      two BaMMV isolates. Phylogenetic analyses indicate that BaYMV and BaMMV were
      largely grouped based on geographical regions such as Asia and Europe. Single
      nucleotide polymorphisms analyses suggested that most BaYMV and BaMMV showed
      strong genetic variations; however, BaYMV isolate Jeonju and BaMMV isolate Gunsan
      exhibited a few and no SNPs, respectively, suggesting low level of genetic
      variation. Taken together, this is the first study of barley RNA viromes in
      Korea.

PMID- 30185903
TI  - Coupling of bone resorption and formation by RANKL reverse signalling.
AB  - Receptor activator of nuclear factor-kappa B (RANK) ligand (RANKL) binds RANK on
      the surface of osteoclast precursors to trigger osteoclastogenesis. Recent
      studies have indicated that osteocytic RANKL has an important role in
      osteoclastogenesis during bone remodelling; however, the role of osteoblastic
      RANKL remains unclear. Here we show that vesicular RANK, which is secreted from
      the maturing osteoclasts, binds osteoblastic RANKL and promotes bone formation by
      triggering RANKL reverse signalling, which activates Runt-related transcription
      factor 2 (Runx2). The proline-rich motif in the RANKL cytoplasmic tail is
      required for reverse signalling, and a RANKL(Pro29Ala) point mutation reduces
      activation of the reverse signalling pathway. The coupling of bone resorption and
      formation is disrupted in RANKL(Pro29Ala) mutant mice, indicating that
      osteoblastic RANKL functions as a coupling signal acceptor that recognizes
      vesicular RANK. RANKL reverse signalling is therefore a potential pharmacological
      target for avoiding the reduced bone formation associated with inhibition of
      osteoclastogenesis.

PMID- 30185902
TI  - Body mass index modulates the association between CDKAL1 rs10946398 variant and
      type 2 diabetes among Taiwanese women.
AB  - CDKAL1 rs10946398 is a type 2 diabetes (T2D)-associated variant. It is a new body
      mass index (BMI)-associated variant in Asian populations. We investigated the
      association between rs10946398 and T2D among 9908 participants aged 30-70 years
      based on BMI: normal weight; 18.5 <= BMI < 24 kg/m2, overweight; 24 <= BMI < 27
      kg/m2, and obesity; BMI >=27 kg/m2. The CC genotype conferred a higher risk of
      T2D than the CA genotype. The odds ratios (ORs) were 1.83; 95% confidence
      interval (CI) 1.49-2.26 and 1.20; 95% CI 1.02-1.40, respectively. The C allele
      was the significant risk allele compared with A allele (OR = 1.32; 95% CI 1.19
      1.47). For normal, overweight and obese participants with CC genotype, the ORs
      were respectively 1.69; 95% CI 1.02-2.81, 2.34; 95% CI 1.50-3.66, and 1.58; 95%
      CI 1.02-2.45 among men and 1.22; 95% CI 0.67-2.22, 2.42; 95% CI 1.30-4.52, and
      2.3; 95% CI 1.19-4.50 among women. The C allele ORs were higher in obese and
      overweight women. In conclusion, the rs10946398 CC/CA genotypes, as well as the C
      allele increased the risk of T2D. The ORs were higher in women who were
      overweight and obese than in those with normal weight. Nonetheless, significant
      results were prominent only among those with CC genotype and C allele.

PMID- 30185904
TI  - Superluminal motion of a relativistic jet in the neutron-star merger GW170817.
AB  - The binary neutron-star merger GW1708171 was accompanied by radiation across the
      electromagnetic spectrum2 and localized2 to the galaxy NGC 4993 at a distance3 of
      about 41 megaparsecs from Earth. The radio and X-ray afterglows of GW170817
      exhibited delayed onset4-7, a gradual increase8 in the emission with time
      (proportional to t0.8) to a peak about 150 days after the merger event9, followed
      by a relatively rapid decline9,10. So far, various models have been proposed to
      explain the afterglow emission, including a choked-jet cocoon4,8,11-13 and a
      successful-jet cocoon4,8,11-18 (also called a structured jet). However, the
      observational data have remained inconclusive10,15,19,20 as to whether GW170817
      launched a successful relativistic jet. Here we report radio observations using
      very long-baseline interferometry. We find that the compact radio source
      associated with GW170817 exhibits superluminal apparent motion between 75 days
      and 230 days after the merger event. This measurement breaks the degeneracy
      between the choked- and successful-jet cocoon models and indicates that, although
      the early-time radio emission was powered by a wide-angle outflow8 (a cocoon),
      the late-time emission was most probably dominated by an energetic and narrowly
      collimated jet (with an opening angle of less than five degrees) and observed
      from a viewing angle of about 20 degrees. The imaging of a collimated
      relativistic outflow emerging from GW170817 adds substantial weight to the
      evidence linking binary neutron-star mergers and short gamma-ray bursts.

PMID- 30185906
TI  - Extensive sex differences at the initiation of genetic recombination.
AB  - Meiotic recombination differs between males and females; however, when and how
      these differences are established is unknown. Here we identify extensive sex
      differences at the initiation of recombination by mapping hotspots of meiotic DNA
      double-strand breaks in male and female mice. Contrary to past findings in
      humans, few hotspots are used uniquely in either sex. Instead, grossly different
      recombination landscapes result from up to fifteen-fold differences in hotspot
      usage between males and females. Indeed, most recombination occurs at sex-biased
      hotspots. Sex-biased hotspots seem to be partly determined by chromosome
      structure, and DNA methylation, which is absent in females at the onset of
      meiosis, has a substantial role. Sex differences are also evident later in
      meiosis as the rate at which meiotic breaks are repaired as crossovers differs
      between males and females in distal regions. The suppression of distal crossovers
      may help to minimize age-related aneuploidy that arises owing to cohesion loss
      during dictyate arrest in females.

PMID- 30185905
TI  - A homing system targets therapeutic T cells to brain cancer.
AB  - Successful T cell immunotherapy for brain cancer requires that the T cells can
      access tumour tissues, but this has been difficult to achieve. Here we show that,
      in contrast to inflammatory brain diseases such as multiple sclerosis, where
      endothelial cells upregulate ICAM1 and VCAM1 to guide the extravasation of pro
      inflammatory cells, cancer endothelium downregulates these molecules to evade
      immune recognition. By contrast, we found that cancer endothelium upregulates
      activated leukocyte cell adhesion molecule (ALCAM), which allowed us to overcome
      this immune-evasion mechanism by creating an ALCAM-restricted homing system (HS).
      We re-engineered the natural ligand of ALCAM, CD6, in a manner that triggers
      initial anchorage of T cells to ALCAM and conditionally mediates a secondary wave
      of adhesion by sensitizing T cells to low-level ICAM1 on the cancer endothelium,
      thereby creating the adhesion forces necessary to capture T cells from the
      bloodstream. Cytotoxic HS T cells robustly infiltrated brain cancers after
      intravenous injection and exhibited potent antitumour activity. We have therefore
      developed a molecule that targets the delivery of T cells to brain cancer.

PMID- 30185907
TI  - A fluid-to-solid jamming transition underlies vertebrate body axis elongation.
AB  - Just as in clay moulding or glass blowing, physically sculpting biological
      structures requires the constituent material to locally flow like a fluid while
      maintaining overall mechanical integrity like a solid. Disordered soft materials,
      such as foams, emulsions and colloidal suspensions, switch from fluid-like to
      solid-like behaviours at a jamming transition1-4. Similarly, cell collectives
      have been shown to display glassy dynamics in 2D and 3D5,6 and jamming in
      cultured epithelial monolayers7,8, behaviours recently predicted theoretically9
      11 and proposed to influence asthma pathobiology8 and tumour progression12.
      However, little is known about whether these seemingly universal behaviours occur
      in vivo13 and, specifically, whether they play any functional part during
      embryonic morphogenesis. Here, by combining direct in vivo measurements of tissue
      mechanics with analysis of cellular dynamics, we show that during vertebrate body
      axis elongation, posterior tissues undergo a jamming transition from a fluid-like
      behaviour at the extending end, the mesodermal progenitor zone, to a solid-like
      behaviour in the presomitic mesoderm. We uncover an anteroposterior, N-cadherin
      dependent gradient in yield stress that provides increasing mechanical integrity
      to the presomitic mesoderm, consistent with the tissue transiting from a wetter
      to a dryer foam-like architecture. Our results show that cell-scale stresses
      fluctuate rapidly (within about 1 min), enabling cell rearrangements and
      effectively 'melting' the tissue at the growing end. Persistent (more than 0.5 h)
      stresses at supracellular scales, rather than cell-scale stresses, guide
      morphogenetic flows in fluid-like tissue regions. Unidirectional axis extension
      is sustained by the reported rigidification of the presomitic mesoderm, which
      mechanically supports posterior, fluid-like tissues during remodelling before
      their maturation. The spatiotemporal control of fluid-like and solid-like tissue
      states may represent a generic physical mechanism of embryonic morphogenesis.

PMID- 30185908
TI  - Deterministic teleportation of a quantum gate between two logical qubits.
AB  - A quantum computer has the potential to efficiently solve problems that are
      intractable for classical computers. However, constructing a large-scale quantum
      processor is challenging because of the errors and noise that are inherent in
      real-world quantum systems. One approach to addressing this challenge is to
      utilize modularity-a strategy used frequently in nature and engineering to build
      complex systems robustly. Such an approach manages complexity and uncertainty by
      assembling small, specialized components into a larger architecture. These
      considerations have motivated the development of a quantum modular architecture,
      in which separate quantum systems are connected into a quantum network via
      communication channels1,2. In this architecture, an essential tool for universal
      quantum computation is the teleportation of an entangling quantum gate3-5, but
      such teleportation has hitherto not been realized as a deterministic operation.
      Here we experimentally demonstrate the teleportation of a controlled-NOT (CNOT)
      gate, which we make deterministic by using real-time adaptive control. In
      addition, we take a crucial step towards implementing robust, error-correctable
      modules by enacting the gate between two logical qubits, encoding quantum
      information redundantly in the states of superconducting cavities6. By using such
      an error-correctable encoding, our teleported gate achieves a process fidelity of
      79 per cent. Teleported gates have implications for fault-tolerant quantum
      computation3, and when realized within a network can have broad applications in
      quantum communication, metrology and simulations1,2,7. Our results illustrate a
      compelling approach for implementing multi-qubit operations on logical qubits
      and, if integrated with quantum error-correction protocols, indicate a promising
      path towards fault-tolerant quantum computation using a modular architecture.

PMID- 30185909
TI  - In vivo reprogramming of wound-resident cells generates skin epithelial tissue.
AB  - Large cutaneous ulcers are, in severe cases, life threatening1,2. As the global
      population ages, non-healing ulcers are becoming increasingly common1,2.
      Treatment currently requires the transplantation of pre-existing epithelial
      components, such as skin grafts, or therapy using cultured cells2. Here we
      develop alternative supplies of epidermal coverage for the treatment of these
      kinds of wounds. We generated expandable epithelial tissues using in vivo
      reprogramming of wound-resident mesenchymal cells. Transduction of four
      transcription factors that specify the skin-cell lineage enabled efficient and
      rapid de novo epithelialization from the surface of cutaneous ulcers in mice. Our
      findings may provide a new therapeutic avenue for treating skin wounds and could
      be extended to other disease situations in which tissue homeostasis and repair
      are impaired.

PMID- 30185910
TI  - Population dynamics of normal human blood inferred from somatic mutations.
AB  - Haematopoietic stem cells drive blood production, but their population size and
      lifetime dynamics have not been quantified directly in humans. Here we identified
      129,582 spontaneous, genome-wide somatic mutations in 140 single-cell-derived
      haematopoietic stem and progenitor colonies from a healthy 59-year-old man and
      applied population-genetics approaches to reconstruct clonal dynamics. Cell
      divisions from early embryogenesis were evident in the phylogenetic tree; all
      blood cells were derived from a common ancestor that preceded gastrulation. The
      size of the stem cell population grew steadily in early life, reaching a stable
      plateau by adolescence. We estimate the numbers of haematopoietic stem cells that
      are actively making white blood cells at any one time to be in the range of
      50,000-200,000. We observed adult haematopoietic stem cell clones that generate
      multilineage outputs, including granulocytes and B lymphocytes. Harnessing
      naturally occurring mutations to report the clonal architecture of an organ
      enables the high-resolution reconstruction of somatic cell dynamics in humans.

PMID- 30185913
TI  - Oncometabolite mechanism unravelled.

PMID- 30185911
TI  - Cxcr1 mediates recruitment of neutrophils and supports proliferation of tumor
      initiating astrocytes in vivo.
AB  - Neutrophils are first-responders to sites of infection and tissue damage
      including the inflamed tumor microenvironment. Increasing evidence suggests that
      crosstalk between tumors and neutrophils can affect the progression of
      established tumors. However, there is a gap in our understanding of the early
      events that lead to neutrophil recruitment to oncogene-transformed cells and how
      these pathways alter tumor progression. Here, we use optically transparent
      zebrafish larvae to probe the early signals that mediate neutrophil recruitment
      to Kras-transformed astrocytes. We show that zebrafish larvae with impaired
      neutrophil function exhibit reduced proliferation of transformed astrocytes
      supporting a critical role for tumor-associated neutrophils in the early
      progression of tumorigenesis. Moreover, using mutants and pharmacological
      inhibition, we show that the chemokine receptor Cxcr1 promotes neutrophil
      recruitment, proliferation of tumor-initiating cells, and neoplastic mass
      formation. These findings highlight the power of the larval zebrafish system to
      image and probe early events in the tumor-initiating microenvironment and
      demonstrate the potential for neutrophil recruitment signaling pathways such as
      Cxcl8-Cxcr1 as targets for anti-cancer therapies.

PMID- 30185915
TI  - Inflammasomes in the gastrointestinal tract: infection, cancer and gut microbiota
      homeostasis.
AB  - Inflammasome signalling is an emerging pillar of innate immunity and has a
      central role in the regulation of gastrointestinal health and disease. Activation
      of the inflammasome complex mediates both the release of the pro-inflammatory
      cytokines IL-1beta and IL-18 and the execution of a form of inflammatory cell
      death known as pyroptosis. In most cases, these mediators of inflammation provide
      protection against bacterial, viral and protozoal infections. However, unchecked
      inflammasome activities perpetuate chronic inflammation, which underpins the
      molecular and pathophysiological basis of gastritis, IBD, upper and lower
      gastrointestinal cancer, nonalcoholic fatty liver disease and obesity. Studies
      have also highlighted an inflammasome signature in the maintenance of gut
      microbiota and gut-brain homeostasis. Harnessing the immunomodulatory properties
      of the inflammasome could transform clinical practice in the treatment of acute
      and chronic gastrointestinal and extragastrointestinal diseases. This Review
      presents an overview of inflammasome biology in gastrointestinal health and
      disease and describes the value of experimental and pharmacological intervention
      in the treatment of inflammasome-associated clinical manifestations.

PMID- 30185914
TI  - Impact of energy dissipation on interface shapes and on rates for dewetting from
      liquid substrates.
AB  - We revisit the fundamental problem of liquid-liquid dewetting and perform a
      detailed comparison of theoretical predictions based on thin-film models with
      experimental measurements obtained by atomic force microscopy. Specifically, we
      consider the dewetting of a liquid polystyrene layer from a liquid polymethyl
      methacrylate layer, where the thicknesses and the viscosities of both layers are
      similar. Using experimentally determined system parameters like viscosity and
      surface tension, an excellent agreement of experimentally and theoretically
      obtained rim profile shapes are obtained including the liquid-liquid interface
      and even dewetting rates. Our new energetic approach additionally allows to
      assess the physical importance of different contributions to the energy
      dissipation mechanism, for which we analyze the local flow fields and the local
      dissipation rates. Using this approach, we explain why dewetting rates for liquid
      liquid systems follow no universal power law, despite the fact that experimental
      velocities are almost constant. This is in contrast to dewetting scenarios on
      solid substrates and in contrast to previous results for liquid-liquid substrates
      using heuristic approaches.

PMID- 30185916
TI  - The metabolic role of vagal afferent innervation.
AB  - The regulation of energy and glucose balance contributes to whole-body metabolic
      homeostasis, and such metabolic regulation is disrupted in obesity and diabetes.
      Metabolic homeostasis is orchestrated partly in response to nutrient and vagal
      dependent gut-initiated functions. Specifically, the sensory and motor fibres of
      the vagus nerve transmit intestinal signals to the central nervous system and
      exert biological and physiological responses. In the past decade, the
      understanding of the regulation of vagal afferent signals and of the associated
      metabolic effect on whole-body energy and glucose balance has progressed. This
      Review highlights the contributions made to the understanding of the vagal
      afferent system and examines the integrative role of the vagal afferent in
      gastrointestinal regulation of appetite and glucose homeostasis. Investigating
      the integrative and metabolic role of vagal afferent signalling represents a
      potential strategy to discover novel therapeutic targets to restore energy and
      glucose balance in diabetes and obesity.

PMID- 30185912
TI  - Functional diversity of brain networks supports consciousness and verbal
      intelligence.
AB  - How are the myriad stimuli arriving at our senses transformed into conscious
      thought? To address this question, in a series of studies, we asked whether a
      common mechanism underlies loss of information processing in unconscious states
      across different conditions, which could shed light on the brain mechanisms of
      conscious cognition. With a novel approach, we brought together for the first
      time, data from the same paradigm-a highly engaging auditory-only narrative-in
      three independent domains: anesthesia-induced unconsciousness, unconsciousness
      after brain injury, and individual differences in intellectual abilities during
      conscious cognition. During external stimulation in the unconscious state, the
      functional differentiation between the auditory and fronto-parietal systems
      decreased significantly relatively to the conscious state. Conversely, we found
      that stronger functional differentiation between these systems in response to
      external stimulation predicted higher intellectual abilities during conscious
      cognition, in particular higher verbal acuity scores in independent cognitive
      testing battery. These convergent findings suggest that the responsivity of
      sensory and higher-order brain systems to external stimulation, especially
      through the diversification of their functional responses is an essential feature
      of conscious cognition and verbal intelligence.

PMID- 30185917
TI  - Numerical Simulation of Particulate Matter 2.5 Distribution in a Roadway.
AB  - Large amounts of dust particles pose serious hazards to the health and safety of
      China's coal miners during roadway blasting processes. It is known that among
      these dust particles, Particulate Matter 2.5 (PM2.5) does the greatest amount of
      harm. In order to study the distributions of the PM2.5 in roadway blasting
      processes, a mathematical model of the gas-solid two-phase flow was established
      in this study, which was based on a Direct Simulation Monte Carlo Method (DSMC).
      Then, a multiphase flow program was developed. This study's results indicated
      that following the blasting processes, fine dust particles gradually floated up
      and were suspended for long durations in the underground roadway space. The
      medium-sized dust particles slowly sink to the ground and were eventually
      expelled before settling to the floor of the roadway. The coarse particles were
      rapidly settled to the roadway floor. It was determined that the PM2.5 particles
      in the front end of the dust group could not be quickly diluted, and the
      concentrations were high until it is expelled from the roadway, whereas the PM2.5
      dust particles in the back end of the underground roadway were found to be
      gradually diluted. Eventually, the PM2.5 concentrations exhibited an alternating
      thin to dense phase distribution. When compared with the Particulate Matter 5
      (PM5), it was found that the PM2.5 was more difficult to discharge, and easily
      formed serious PM2.5 dust air pollution. This study's results were determined to
      be conductive to the future control of PM2.5 in the underground roadway blasting
      processes.

PMID- 30185918
TI  - Impact of mangrove forests degradation on biodiversity and ecosystem functioning.
AB  - Mangroves are amongst the most productive marine ecosystems on Earth, providing a
      unique habitat opportunity for many species and key goods and services for human
      beings. Mangrove habitats are regressing at an alarming rate, due to direct
      anthropogenic impacts and global change. Here, in order to assess the effects of
      mangrove habitat degradation on benthic biodiversity and ecosystem functioning,
      we investigated meiofaunal biodiversity (as proxy of benthic biodiversity),
      benthic biomass and prokaryotic heterotrophic production (as proxies of ecosystem
      functioning) and trophic state in a disturbed and an undisturbed mangrove
      forests. We report here that disturbed mangrove area showed a loss of 20% of
      benthic biodiversity, with the local extinction of four Phyla (Cladocera,
      Kynorincha, Priapulida, Tanaidacea), a loss of 80% of microbial-mediated
      decomposition rates, of the benthic biomass and of the trophic resources. The
      results of this study strengthen the need to preserve mangrove forests and to
      restore those degraded to guarantee the provision of goods and services needed to
      support the biodiversity and functioning of wide portions of tropical ecosystems.

PMID- 30185920
TI  - Functional imagery training versus motivational interviewing for weight loss: a
      randomised controlled trial of brief individual interventions for overweight and
      obesity.
AB  - OBJECTIVE: Functional Imagery Training (FIT) is a new brief motivational
      intervention based on the Elaborated Intrusion theory of desire. FIT trains the
      habitual use of personalised, affective, goal-directed mental imagery to plan
      behaviours, anticipate obstacles, and mentally try out solutions from previous
      successes. It is delivered in the client-centred style of Motivational
      Interviewing (MI). We tested the impact of FIT on weight loss, compared with time
      and contact-matched MI. DESIGN: We recruited 141 adults with BMI (kg/m2) >=25,
      via a community newspaper, to a single-centre randomised controlled trial.
      Participants were allocated to one of two active interventions: FIT or MI.
      Primary data collection and analyses were conducted by researchers blind to
      interventions. All participants received two sessions of their allocated
      intervention; the first face-to-face (1 h), the second by phone (maximum 45 min).
      Booster calls of up to 15 min were provided every 2 weeks for 3 months, then once
      monthly until 6 months. Maximum contact time was 4 h of individual consultation.
      Participants were assessed at Baseline, at the end of the intervention phase (6
      months), and again 12 months post-baseline. MAIN OUTCOME MEASURES: Weight (kg)
      and waist circumference (WC, cm) reductions at 6 and 12 months. RESULTS: FIT
      participants (N = 59) lost 4.11 kg and 7.02 cm of WC, compared to .74 kg and 2.72
      cm in the MI group (N = 55) at 6 months (weight mean difference (WMD) = 3.37 kg,
      p < .001, 95% CI [-5.2, -2.1], waist-circumference mean difference (WCMD) = 4.3
      cm, p < .001, 95% CI [-6.3,-2.6]). Between-group differences were maintained and
      increased at month 12: FIT participants lost 6.44 kg (W) and 9.1 cm (WC) compared
      to the MI who lost .67 kg and 2.46 cm (WMD = 5.77 kg, p < .001, 95% CI [-7.5, 
      4.4], WCMD = 6.64 cm, p < .001, 95% CI [-7.5, -4.4]). CONCLUSION: FIT is a
      theoretically informed motivational intervention which offers substantial
      benefits for weight loss and maintenance of weight reduction, compared with MI
      alone, despite including no lifestyle education or advice.

PMID- 30185919
TI  - Dynamics of neural representations when searching for exemplars and categories of
      human and non-human faces.
AB  - Face perception abilities in humans exhibit a marked expertise in distinguishing
      individual human faces at the expense of individual faces from other species (the
      other-species effect). In particular, one behavioural effect of such
      specialization is that human adults search for and find categories of non-human
      faces faster and more accurately than a specific non-human face, and vice versa
      for human faces. However, a recent visual search study showed that neural
      responses (event-related potentials, ERPs) were identical when finding either a
      non-human or human face. We used time-resolved multivariate pattern analysis of
      the EEG data from that study to investigate the dynamics of neural
      representations during a visual search for own-species (human) or other-species
      (non-human ape) faces, with greater sensitivity than traditional ERP analyses.
      The location of each target (i.e., right or left) could be decoded from the EEG,
      with similar accuracy for human and non-human faces. However, the neural patterns
      associated with searching for an exemplar versus a category target differed for
      human faces compared to non-human faces: Exemplar representations could be more
      reliably distinguished from category representations for human than non-human
      faces. These findings suggest that the other-species effect modulates the nature
      of representations, but preserves the attentional selection of target items based
      on these representations.

PMID- 30185921
TI  - Brown adipose tissue in prepubertal children: associations with sex, birthweight,
      and metabolic profile.
AB  - BACKGROUND/OBJECTIVES: Individuals born small-for-gestational age (SGA),
      especially those who experience postnatal catch-up growth, are at increased risk
      for developing endocrine-metabolic abnormalities before puberty. In adults, brown
      adipose tissue (BAT) has been associated with protection against metabolic
      disorders, such as obesity, type 2 diabetes, and dyslipidaemia. Here, we assessed
      for the first time whether BAT activation differs between prepubertal children
      born SGA or appropriate-for-gestational age (AGA). SUBJECTS/METHODS: The study
      population consisted of 86 prepubertal children [41 AGA and 45 SGA; age (mean +/-
      SEM), 8.5 +/- 0.1 years], recruited into two prospective longitudinal studies
      assessing endocrine-metabolic status and body composition in infancy and
      childhood. The temperature at the supraclavicular region (SCR) before and after a
      cold stimulus was measured by infrared thermal imaging, and the area of thermally
      active SCR (increase after cold challenge, DeltaAreaSCR) was calculated as a
      surrogate index of BAT activation. The results were correlated with clinical,
      endocrine-metabolic, and inflammation variables, and with visceral and hepatic
      adiposity (assessed by Magnetic Resonance Imaging). RESULTS: No differences in
      BAT activation index, as judged by DeltaAreaSCR, were found between AGA and SGA
      children. However, girls showed higher baseline and post-cold induction AreaSCR
      than boys (both p <= 0.01). An interaction between gender and birth weight
      subgroup was observed for BAT activation; AGA girls increased significantly the
      DeltaAreaSCR as compared to AGA boys; this increase did not occur in SGA girls vs
      SGA boys. Cold-induced DeltaAreaSCR negatively correlated with HOMA-IR, us-CRP,
      liver volume, and liver fat. CONCLUSIONS: Prepubertal AGA girls had significantly
      greater BAT activation index as compared to AGA boys; this difference was not
      observed in SGA subjects. Higher BAT activation associated with a lower amount of
      visceral fat and with a favorable metabolic profile. Long-term follow-up is
      needed to determine whether those differences relate to pubertal timing, and to
      the development of obesity and metabolic disorders.

PMID- 30185922
TI  - The ESRC Strategic Network for Obesity: tackling obesity with big data.

PMID- 30185923
TI  - Emergent memory in cell signaling: Persistent adaptive dynamics in cascades can
      arise from the diversity of relaxation time-scales.
AB  - The mitogen-activated protein kinase (MAPK) signaling cascade, an evolutionarily
      conserved motif present in all eukaryotic cells, is involved in coordinating
      crucial cellular functions. While the asymptotic dynamical behavior of the
      pathway stimulated by a time-invariant signal is relatively well-understood, we
      show using a computational model that it exhibits a rich repertoire of transient
      adaptive responses to changes in stimuli. When the signal is switched on, the
      response is characterized by long-lived modulations in frequency as well as
      amplitude. On withdrawing the stimulus, the activity decays over long timescales,
      exhibiting reverberations characterized by repeated spiking in the activated MAPK
      concentration. The long-term persistence of such post-stimulus activity suggests
      that the cascade retains memory of the signal for a significant duration
      following its removal. The molecular mechanism underlying the reverberatory
      activity is related to the existence of distinct relaxation rates for the
      different cascade components. This results in the imbalance of fluxes between
      different layers of the cascade, with the reuse of activated kinases as enzymes
      when they are released from sequestration in complexes. The persistent adaptive
      response, indicative of a cellular "short-term" memory, suggests that this
      ubiquitous signaling pathway plays an even more central role in information
      processing by eukaryotic cells.

PMID- 30185924
TI  - Complex fine-scale spatial genetic structure in Epidendrum rhopalostele: an
      epiphytic orchid.
AB  - Orchid seeds are presumably dispersed by wind due to their very small size and
      thus can potentially travel long distances. However, the few related studies
      indicate that seeds fall close to their mother plants. Because seed dispersal and
      colonization patterns can have relevant consequences for long-term species
      persistence, we assessed the fine-scale genetic structure of the epiphytic orchid
      Epidendrum rhopalostele to provide insight into these patterns. All individuals
      in the studied population were georeferenced and genotyped with AFLP-markers.
      Genetic structure was evaluated at two levels (forest and tree) using three
      approaches: principal coordinates analysis, model-based clustering, and spatial
      autocorrelation analysis. Results showed two genetic groups, composed of
      individuals from almost every tree with orchids. Spatial autocorrelation analysis
      at the forest level found no significant genetic structure when all individuals
      were considered, but a pattern of genetic patches was revealed when the analysis
      was performed separately for each group. Genetic patches had an estimated
      diameter of 4 m and were composed of individuals from more than one tree. A weak
      genetic structure was detected at the tree level at distances less than 1.5 m.
      These results suggest that many seeds fall close to the mother plant and become
      established in the same host tree. Additionally, a sequential colonization
      process seems to be the predominant mode of expansion, whereby progeny from
      orchids in one tree colonize neighboring trees. Thus, the existence of two
      distinct genetic groups and the presence of genetic patches should be considered
      when seed sampling for ex situ conservation.

PMID- 30185925
TI  - Analysis of QTLs on heading date based on single segment substitution lines in
      rice (Oryza Sativa L.).
AB  - Single segment substitution lines (SSSLs) have been confirmed to be powerful
      tools to perform quantitative trait locus (QTL) analysis. This study illuminated
      the process and methods of QTL analysis with SSSLs on heading date (HD) in rice.
      QTL identification under two cropping seasons revealed 98 of 202 SSSLs associated
      with HD. A total of 22 QTLs were positioned in relative narrow regions on
      chromosomes by mrMLM.GUI software. QTL qHd3-1 was precisely positioned at 4.4 cM
      on chromosome 3 by a secondary F2 population. Through SSSL pyramiding, double
      segment substitution lines were constructed and used to analyze epistatic
      interactions of digenic loci. Epistatic effects for three pairs of QTLs were
      estimated, indicating the interactions of QTL qHd3-1 with other QTLs detected and
      the role to enhance the expression of early ripening or restraining of late
      flowering QTLs. Additionally, analysis of QTL in different environments provided
      information about the stability of HD QTLs. This type of research points out the
      way to excavate favorable genes for design breeding.

PMID- 30185926
TI  - Stretchable and Washable Strain Sensor Based on Cracking Structure for Human
      Motion Monitoring.
AB  - Stretchable and wearable strain sensors have been intensively studied in recent
      years for applications in human motion monitoring. However, achieving a high
      performance strain sensor with high stretchability, ultra-sensitivity, and
      functionality, such as tunable sensing ranges and sensitivity to various stimuli,
      has not yet been reported, even though such sensors have great importance for the
      future applications of wearable electronics. Herein, a novel and versatile strain
      sensor based on a cracking (silver ink patterned silicone elastomer)-(silver
      plated nylon structure) (Ag-DS/CF) has been designed and fabricated. The unique
      structure combined precisely shaped stretchable conductive fabrics and wrinkled
      Ag-ink pattern to achieve an excellent electrical performance. The Ag-DS/CF could
      be used to detect both large and subtle human motions and activities, pressure
      changes, and physical vibrations by achieving high stretchability up to 75%,
      ultrahigh sensitivity (gauge factor >104-106), tunable sensing ranges (from 7 to
      75%). Excellent durability was demonstrated for human motion monitoring with
      machine washability. The extremely versatile Ag-DS/CF showed outstanding
      potential for the future of wearable electronics in real-time monitoring of human
      health, sports performance, etc.

PMID- 30185929
TI  - Bacteria-primed T cells identified as culprit in glaucoma.

PMID- 30185927
TI  - Effects of uric acid on vascular endothelial function from bedside to bench.
AB  - This study was designed to investigate the effects of uric acid on vascular
      endothelial function in measurements carried out either at the bedside or the
      laboratory bench. First, we performed reactive hyperemia peripheral arterial
      tonometry using an EndoPAT 2000 device and measured serum uric acid levels in 92
      outpatients with hypertension. The reactive hyperemia index (RHI) showed no
      correlation with serum uric acid level (R = -0.125, P = 0.235) in either overall
      patients or in a high-risk group of 51 patients with complications such as
      cardiovascular and cerebrovascular diseases, chronic kidney disease, and/or
      diabetes (R = -0.025, P = 0.860). However, in the remaining 41 patients in the
      low-risk group, RHI correlated negatively with serum uric acid level (R = -0.335,
      P = 0.032). Multiple regression analysis showed that serum uric acid level
      predicted RHI (R = -0.321, P = 0.043) in the low-risk group independent of age,
      body mass index, systolic blood pressure, and low density lipoprotein-cholesterol
      level. We then performed an in-vitro study using the WST-8 assay in human
      umbilical vein endothelial cells, which showed that hypoxic conditions reduced
      cell viability. Treatment with uric acid caused a further reduction in cell
      viability, while ascorbic acid improved viability. Using Western blot analysis,
      we observed that uric acid reduced endothelial nitric oxide synthase
      phosphorylation during hypoxic conditions. Serum uric acid level is associated
      with peripheral vascular endothelial function in patients with low-risk
      hypertension and uric acid could directly impair endothelial function under
      hypoxic conditions. These results are relevant to the interventional studies
      examining the cardiovascular protective effect of hypouricemic agents.

PMID- 30185928
TI  - Computational and neural signatures of pre and post-sensory expectation bias in
      inferior temporal cortex.
AB  - As we gather noisy sensory information from the environment, prior knowledge
      about the likely cause(s) of sensory input can be leveraged to facilitate
      perceptual judgments. Here, we investigated the computational and neural
      manifestation of cued expectations in human subjects as they performed a
      probabilistic face/house discrimination task in which face and house stimuli were
      preceded by informative or neutral cues. Drift-diffusion modeling of behavioral
      data showed that cued expectations biased both the baseline (pre-sensory) and
      drift-rate (post-sensory) of evidence accumulation. By employing a catch-trial
      functional MRI design we were able to isolate neural signatures of expectation
      during pre- and post-sensory stages of decision processing in face- and house
      selective areas of inferior temporal cortex (ITC). Cue-evoked timecourses were
      modulated by cues in a manner consistent with a pre-sensory prediction signal
      that scaled with probability. Sensory-evoked timecourses resembled a prediction
      error signal, greater in magnitude for surprising than expected stimuli.
      Individual differences in baseline and drift-rate biases showed a clear mapping
      onto pre- and post-sensory fMRI activity in ITC. These findings highlight the
      specificity of perceptual expectations and provide new insight into the
      convergence of top-down and bottom-up signals in ITC and their distinct
      interactions prior to and during sensory processing.

PMID- 30185930
TI  - No supplementary evidence of attention to a spatial cue when saccadic
      facilitation is absent.
AB  - Attending a location in space facilitates responses to targets at that location
      when the time between cue and target is short. Certain types of exogenous cues -
      such as sudden peripheral onsets - have been described as reflexive and
      automatic. Recent studies however, have been showing many cases where exogenous
      cues are less automatic than previously believed and do not always result in
      facilitation. A lack of the behavioral facilitation, however, does not
      automatically necessitate a lack of underlying attention to that location. We
      test exogenous cueing in two experiments where facilitation is and is not likely
      to be observed with saccadic responses. We also test alternate measures linked to
      the allocation of attention such as saccadic curvature, microsaccades and pupil
      size. As expected, we find early facilitation as measured by saccadic reaction
      time when CTOAs are predictable but not when they are randomized within a block.
      We find no impact of the cue on microsaccade direction for either experiment, and
      only a slight dip in the frequency of microsaccades after the cue. We do find
      that change in pupil size to the cue predicts the magnitude of the validity
      effect, but only in the experiment where facilitation was observed. In both
      experiments, we observed a tendency for saccadic curvature to deviate away from
      the cued location and this was stronger for early CTOAs and toward vertical
      targets. Overall, we find that only change in pupil size is consistent with
      observed facilitation. Saccadic curvature is influenced by the onset of the cue,
      buts its direction is indicative of oculomotor inhibition whether we see RT
      facilitation or not. Microsaccades were not diagnostic in either experiment.
      Finally, we see little to no evidence of attention at the cued location in any
      additional measures when facilitation of saccadic responses is absent.

PMID- 30185932
TI  - Efficacy of daily supplementation of 800 IU vitamin D on vitamin D status at 6
      months of age in term healthy Indian infants.
AB  - OBJECTIVES: Most authorities recommend daily supplementation of 400 IU vitamin D
      for all term healthy neonates throughout infancy, however this dose was shown to
      be inadequate in an earlier study from our institution. We planned to evaluate if
      supplementation of 800 IU/day in term Indian infants would reduce the prevalence
      of vitamin D insufficiency (VDI) at 6 months of age. METHODS: In a prospective
      study, we supplemented 800 IU/day of vitamin D in 70 term infants from birth till
      6 months of age. Serum 25-hydroxy cholecalciferol [25(OH)D] was measured at birth
      and 6 months for all infants; and at 6, 10 and 14 weeks of age in subsets of 23
      infants each. The primary outcome was prevalence of VDI (defined as serum 25(OH)D
      level < 50 nmol/L) at 6 months of age. RESULTS: A total of 58 out of 70 (83%)
      infants were followed up until 6 months of age. The median (nmol/L; IQR) serum
      25(OH)D at birth and 6 months of age was 25 (12.5-35) and 92.5 (72.5-137.5),
      respectively. The prevalence of VDI at birth was 91.3% (63/69), which reduced to
      6.9% (4/58) at 6 months of age. However, four infants (6.9%, 95% CI 1.9-16.7)
      developed vitamin D excess (serum 25(OH)D 250-375 nmol/L) requiring reduction of
      the dose of supplementation. No infant developed vitamin D toxicity (serum
      25(OH)D > 375 nmol/L). CONCLUSIONS: Daily supplementation of 800 IU of vitamin D
      resulted in vitamin D sufficiency in most term healthy infants at 6 months of age
      but with potential risk of toxicity.

PMID- 30185931
TI  - Thyroid function in neonates of women with subclinical hypothyroidism or
      hypothyroxinemia.
AB  - OBJECTIVE: To assess whether treatment of pregnant women with subclinical
      hypothyroidism or hypothyroxinemia alters neonatal TSH results. STUDY DESIGN: A
      planned secondary analysis of data from two multi-center randomized, double
      masked, placebo-controlled thyroxine replacement trials in pregnant women with
      either subclinical hypothyroidism or hypothyroxinemia. Infant heel-stick
      specimens were obtained before discharge. We compared TSH levels between neonates
      born to mothers allocated to treatment or placebo within each trial and between
      neonates in the placebo groups. Multiples of means were generated for day-of-life
      specific data. RESULTS: Neonatal TSH values were available for 573/677 (84.6%)
      newborns from the subclinical hypothyroidism trial and 461/526 (87.6%) newborns
      from the hypothyroxinemia trial. Neonatal TSH values did not differ in either
      trial by treatment group or between placebo groups (P > 0.05 for all
      comparisons). CONCLUSIONS: Neonatal TSH values did not differ with thyroid
      hormone replacement in pregnancies diagnosed with subclinical hypothyroidism or
      hypothyroxinemia.

PMID- 30185934
TI  - Targeting quiescent leukemic stem cells using second generation autophagy
      inhibitors.
AB  - In chronic myeloid leukemia (CML), tyrosine kinase inhibitor (TKI) treatment
      induces autophagy that promotes survival and TKI-resistance in leukemic stem
      cells (LSCs). In clinical studies hydroxychloroquine (HCQ), the only clinically
      approved autophagy inhibitor, does not consistently inhibit autophagy in cancer
      patients, so more potent autophagy inhibitors are needed. We generated a murine
      model of CML in which autophagic flux can be measured in bone marrow-located
      LSCs. In parallel, we use cell division tracing, phenotyping of primary CML
      cells, and a robust xenotransplantation model of human CML, to investigate the
      effect of Lys05, a highly potent lysosomotropic agent, and PIK-III, a selective
      inhibitor of VPS34, on the survival and function of LSCs. We demonstrate that
      long-term haematopoietic stem cells (LT-HSCs: Lin-Sca-1+c-kit+CD48-CD150+)
      isolated from leukemic mice have higher basal autophagy levels compared with non
      leukemic LT-HSCs and more mature leukemic cells. Additionally, we present that
      while HCQ is ineffective, Lys05-mediated autophagy inhibition reduces LSCs
      quiescence and drives myeloid cell expansion. Furthermore, Lys05 and PIK-III
      reduced the number of primary CML LSCs and target xenografted LSCs when used in
      combination with TKI treatment, providing a strong rationale for clinical use of
      second generation autophagy inhibitors as a novel treatment for CML patients with
      LSC persistence.

PMID- 30185933
TI  - Hemolymph protein profiles of subterranean termite Reticulitermes flavipes
      challenged with methicillin resistant Staphylococcus aureus or Pseudomonas
      aeruginosa.
AB  - When the subterranean termite Reticulitermes flavipes is fed heat-killed
      methicillin resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa, the
      termite produces proteins with antibacterial activity against the inducer
      pathogen in its hemolymph. We used a proteomic approach to characterize the
      alterations in protein profiles caused by the inducer bacterium in the hemolymph
      of the termite. Nano-liquid chromatography-tandem mass spectrometry analysis
      identified a total of 221 proteins and approximately 70% of these proteins could
      be associated with biological processes and molecular functions. Challenges with
      these human pathogens induced a total of 57 proteins (35 in MRSA-challenged, 16
      in P. aeruginosa-challenged, and 6 shared by both treatments) and suppressed 13
      proteins by both pathogens. Quasi-Poisson likelihood modeling with false
      discovery rate adjustment identified a total of 18 and 40 proteins that were
      differentially expressed at least 2.5-fold in response to MRSA and P. aeruginosa
      challenge, respectively. We selected 7 differentially expressed proteins and
      verified their gene expression levels via quantitative real-time RT-PCR. Our
      findings provide an initial insight into a putative termite immune response
      against MRSA and P. aeruginosa-challenge.

PMID- 30185935
TI  - Characterization of an X-chromosome-linked telomere biology disorder in females
      with DKC1 mutation.

PMID- 30185936
TI  - Prescription pattern of alpha-blockers for management of lower urinary tract
      symptoms/benign prostatic hyperplasia.
AB  - This study investigated trends in the prescription of alpha-blockers for patients
      with BPH, focusing on changing patterns of prescriptions during 2002-2013 using
      National Health Insurance Service-National Sample Cohort data. A total of 65,596
      Korean males over 50 years old diagnosed with BPH were identified from the NHIS
      NSC database between 2002-2013. Patterns of each alpha -blocker prescription were
      analyzed and persistence rate, switch rate, and return rate during a follow-up
      period of 3 years after the first prescription were calculated. A total of 28,318
      men over 50 years old (64.95 +/- 9.12), changed medication within six months
      following the first prescription of alpha -blocker. (1) Tamsulosin showed the
      highest persistence rate when compared with other alpha-blockers (2) Among
      patients who switched to a second alpha-blocker, tamsulosin showed the highest
      return rate when compared with other alpha-blockers. Tamsulosin has been the most
      commonly prescribed alpha1-blocker since the mid-2000s, in line with its
      demonstrated highest persistence and return rates. These data probably reflect
      patient satisfaction with alpha1-blockers in the management of BPH, in which the
      decision to stop and switch pharmacological treatments is primarily based on
      changes in symptoms or side effects.

PMID- 30185938
TI  - Exposure characterization and estimation of benchmark dose for cancer biomarkers
      in an occupational cohort of diesel engine testers.
AB  - Exposure to diesel engine exhaust (DEE) was associated with various adverse
      health effects including lung cancer. Particle size distribution and profiles of
      organic compounds in both particle and gas phases of DEE that could provide
      valuable insights into related health effects were measured in a diesel engine
      testing workshop. Concentrations of urinary 6 mono-hydroxylated polycyclic
      aromatic hydrocarbons (OH-PAHs) in 137 DEE-exposed workers and 127 non-DEE
      exposed workers were determined. Benchmark dose method was applied to estimate
      lower limit of benchmark dose (BMDL) of urinary OH-PAHs most specific to DEE
      exposure for previously reported cancer biomarkers. We found that 84.3% of diesel
      exhaust particles were ultrafine particles. Indeno[123-cd]pyrene and phenanthrene
      were the most abundant carcinogenic and noncarcinogenic PAHs in the particle
      phase of DEE, respectively. Principal component analysis demonstrated that
      urinary hydroxyphenanthrene (OHPhe) had highest loading value on principal
      component (PC) representative of DEE exposure and lowest loading value on PC
      representative of smoking status. BMDLs of urinary OHPhe from best-fitting models
      for cancer biomarkers including micronucleus and 1,N6-ethenodeoxyadenosine were
      1.08 MUg/g creatinine and 2.82 MUg/g creatinine, respectively. These results
      provided basis for understanding DEE exposure induced health effects and
      potential threshold for regulating DEE levels in an occupational setting.

PMID- 30185937
TI  - Cortical surface area alterations shaped by genetic load for neuroticism.
AB  - Neuroticism has been shown to act as an important risk factor for major
      depressive disorder (MDD). Genetic and neuroimaging research has independently
      revealed biological correlates of neurotic personality including cortical
      alterations in brain regions of high relevance for affective disorders. Here we
      investigated the influence of a polygenic score for neuroticism (PGS) on cortical
      brain structure in a joint discovery sample of n = 746 healthy controls (HC) and
      n = 268 MDD patients. Findings were validated in an independent replication
      sample (n = 341 HC and n = 263 MDD). Subgroup analyses stratified for case
      control status and analyses of associations between neurotic phenotype and
      cortical measures were carried out. PGS for neuroticism was significantly
      associated with a decreased cortical surface area of the inferior parietal
      cortex, the precuneus, the rostral cingulate cortex and the inferior frontal
      gyrus in the discovery sample. Similar associations between PGS and surface area
      of the inferior parietal cortex and the precuneus were demonstrated in the
      replication sample. Subgroup analyses revealed negative associations in the
      latter regions between PGS and surface area in both HC and MDD subjects. Neurotic
      phenotype was negatively correlated with surface area in similar cortical regions
      including the inferior parietal cortex and the precuneus. No significant
      associations between PGS and cortical thickness were detected. The morphometric
      overlap of associations between both PGS and neurotic phenotype in similar
      cortical regions closely related to internally focused cognition points to the
      potential relevance of genetically shaped cortical alterations in the development
      of neuroticism.

PMID- 30185939
TI  - The association between cumulative cadmium intake and osteoporosis and risk of
      fracture in a Chinese population.
AB  - Bone is one of the target organs for cadmium toxicity. However, few studies have
      shown the association between cumulative cadmium intake and prevalence of
      osteoporosis and bone fracture. In the present study, we evaluated the
      association between cumulative cadmium intake and osteoporosis and risk of
      fracture in a Chinese population. A total of 790 subjects (488 women and 302 men)
      living in a control area and two cadmium-polluted areas were included. The
      cumulative cadmium intake was estimated by a food survey. The bone mineral
      density was determined by using single-photon absorptiometry. The cumulative
      cadmium intakes were 0.48, 2.14, and 11.00 g for men, and 0.42, 2.11, and 11.12 g
      in women in control, and moderately and heavily polluted areas, respectively. In
      women, the odds ratios (ORs) of subjects with a cadmium intake between 2.21 and
      10.63 g and >10.63 g were 1.30 (95% CI: 0.58-2.94) and 2.36 (95% CI: 1.14-5.16),
      compared with those with a cadmium intake < 0.58 g after adjusting to the
      confounders for osteoporosis. The ORs of subjects with a cadmium intake >10.63 g
      were 2.34 (95% CI: 1.23-4.38) for all of the women and 2.62 (95% CI: 1.02-5.58)
      in women >= 60 years old, compared with those with a cadmium intake <10.63 g
      after adjusting to the confounders for bone fractures. In men, similar trends
      were observed, but no statistical significance was found. In addition, those
      subjects with renal tubular dysfunction showed high risk of bone fracture. Our
      results indicate that a high level of cumulative cadmium intake is associated
      with an increased rate of osteoporosis and fractures among women.

PMID- 30185940
TI  - Identification of metabolic profiles associated with human exposure to
      perfluoroalkyl substances.
AB  - Recent epidemiological studies suggest that human exposure to perfluoroalkyl
      substances (PFASs) may be associated with type 2 diabetes and other metabolic
      phenotypes. To gain further insights regarding PFASs exposure in humans, we here
      aimed to characterize the associations between different PFASs and the
      metabolome. In this cross-sectional study, we investigated 965 individuals from
      Sweden (all aged 70 years, 50% women) sampled in 2001-2004. PFASs were analyzed
      in plasma using isotope-dilution ultra-pressure liquid chromatography coupled to
      tandem mass spectrometry (UPLC-MS/MS). Non-target metabolomics profiling was
      performed in plasma using UPLC coupled to time-of-flight mass spectrometry (UPLC
      QTOFMS) operated in positive electrospray mode. Multivariate linear regression
      analysis was used to investigate associations between circulating levels of PFASs
      and metabolites. In total, 15 metabolites, predominantly from lipid pathways,
      were associated with levels of PFASs following adjustment for sex, smoking,
      exercise habits, education, energy, and alcohol intake, after correction for
      multiple testing. Perfluorononanoic acid (PFNA) and perfluoroundecanoic acid
      (PFUnDA) were strongly associated with multiple glycerophosphocholines and fatty
      acids including docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA). We
      also found that the different PFASs evaluated were associated with distinctive
      metabolic profiles, suggesting potentially different biochemical pathways in
      humans.

PMID- 30185941
TI  - The impact of wildfire smoke on compositions of fine particulate matter by
      ecoregion in the Western US.
AB  - Epidemiological studies of wildfire PM2.5 constituents are hindered by the
      limited information on the population exposure to ambient PM2.5 constituents
      during high-pollution episodes from wildfires ("smoke waves"). The chemical
      composition of wildfire-related PM2.5 can be affected by different ecosystems.
      Current literature assessing the differences in PM2.5 pollution from wildfire
      smoke by ecosystems often analyzes air samples collected from the smoke near the
      center of an individual fire, but the results might not represent the exposure of
      the general public living away from the fire center but affected by the smoke of
      the fire. We assessed the population-based exposure to wildfire-related PM2.5
      species by integrating monitor measurements on 29 PM2.5 species and previous
      findings on smoke waves during 2004-2009 in 51 Western US counties across six
      ecoregions. We found that across all ecoregions, smoke waves were associated with
      an increase in the fraction of organic carbon of total PM2.5 by 20 percentage
      points (95% confidence interval (CI): 17, 23), an increase in the fraction of
      elemental carbon by 0.99 percentage points (95% CI: 0.43, 1.6), and decreases in
      fractions of sulfate and crustal species. While the PM2.5 mixtures were dominated
      by the same source (wildfires), compositions in North American Deserts and the
      Great Plains during smoke waves were distinct. Besides expanding the knowledge of
      wildfire PM2.5, our study has implications beyond wildfires and could aid future
      population-based epidemiological research on PM2.5 mixtures by source and region.

PMID- 30185942
TI  - Urinary pesticide concentrations in French adults with low and high organic food
      consumption: results from the general population-based NutriNet-Sante.
AB  - An organic diet may reduce dietary exposure to pesticides but findings based on
      observational data are scant. We aimed to compare urinary pesticide
      concentrations between "organic" and "conventional" consumers from the NutriNet
      Sante study. Organic food consumption was determined using a self-reported food
      frequency questionnaire. Individuals with a proportion of organic food in the
      whole diet (in g/d) below 10% were defined as low organic food consumers and
      those whose proportion was above 50% as high organic food consumers. A propensity
      score matching procedure was then used to obtain two similar subsets of 150
      participants, differing mostly by the organic valence of their diet. Urinary
      pesticide and metabolite concentrations (organophosphorus, pyrethroid, and azole
      compounds) were determined by UPLC-MS/MS, standardized with respect to
      creatinine. The molar sums of total diethylphosphates, dimethylphosphates, and
      dialkylphosphates were also computed. Differences in distributions across groups
      were tested using Wilcoxon signed-rank test for matched data. Mean age was 58.5
      years and 70% of participants were women. Significantly lower urinary levels of
      diethylthiophosphate, dimethylthiophosphate, dialkylphosphates, and free 3
      phenoxybenzoic acid were observed among organic consumers compared to
      conventional consumers. Our findings confirm that exposure to certain
      organophosphate and pyrethroid pesticides in adults may be lowered by switching
      from conventional to organic foods. This is particularly of high interest among
      conventional fruit and vegetable consumers, as their exposure may be the highest.

PMID- 30185943
TI  - Bisphenol A and pubertal height growth in school-aged children.
AB  - BACKGROUND: Bisphenol A (BPA) is an environmental endocrine disruptor and is
      found in many consumer products. Studies suggest that BPA may perturb pubertal
      development, although evidence on BPA-influenced pubertal height growth is
      scarce. METHODS: A total of 754 children aged 9-18 years from three schools (one
      elementary, one middle, and one high school) in Shanghai were included in this
      longitudinal study. Height was measured at enrolment (visit 1) and, subsequently,
      at 19 months after enrolment (visit 2). Age- and sex-specific Z scores for height
      were calculated (height Z score = [participant's height-sex- and age-specific
      population height mean]/sex- and age-specific population height standard
      deviation). Urine samples were collected at enrolment to measure BPA
      concentrations. We used multiple linear regression models or general estimating
      equation models (GEE) to estimate associations between urine BPA level and height
      Z score. RESULTS: The geometric mean of urine BPA concentrations was 1.6 MUg/L
      (95%CI: 1.4, 1.8) or 1.2 MUg/g creatinine (95%CI: 1.0, 1.3). An inverse
      association between urine BPA level and height was observed in boys. After
      adjustment for potential confounders, height Z score at enrolment in boys
      decreased by 0.49 for the highest exposure level (above 10.9 MUg/g creatinine as
      the 90th percentile), compared with the lowest BPA exposure (below 0.2 MUg/g
      creatinine as the 25th percentile) (95%CI: -0.96, -0.01; p-trend = 0.024). The
      inverse association remained between BPA exposure and height Z score at visit 2.
      The GEE model showed that a 1-unit increase in log10-transformed BPA
      concentrations was associated with a 0.15-point decrease in height Z score over
      the follow-up (95%CI: -0.30, -0.01). BPA was not associated with height growth in
      girls. CONCLUSIONS: Our findings indicate an inverse association between urine
      BPA level and height growth in boys. These findings need to be confirmed in
      further studies.

PMID- 30185944
TI  - Aflatoxin exposure in children living in Mirpur, Dhaka: data from MAL-ED
      companion study.
AB  - Dietary exposure to aflatoxin is implicated in growth faltering of children.
      Despite the high burden of childhood stunting in urban Bangladesh, there are no
      data on long-term exposure to aflatoxin. This study aimed to explore aflatoxin
      exposure levels in a group of children followed longitudinally. The current study
      used data and biospecimens collected during 2010-2014 as part of the MAL-ED birth
      cohort study in an urban slum of Mirpur, Dhaka where children were followed from
      birth to 36 months. AFB1-lysine adduct concentrations were determined by isotope
      dilution mass spectrometry from plasma samples collected at 7, 15, 24, and 36
      months of age. The limit of detection was 0.5 pg of AFB1-lys/mg albumin. In 744
      plasma samples, the geometric mean of AFB1-lysine/mg albumin was 1.07 pg (range
      0.04-123.5 pg/mg albumin). The proportion of children with detectable aflatoxin
      exposure was 10.1, 20.9, 17.9, and 61.7% for 7, 15, 24, and 36 months,
      respectively. Reduction in breastfeeding prevalence (80% at 24 months vs. 38% in
      36 months) corresponded with the high-level detection of AFB1-lysine at the age
      of 36 months. AFB1-lysine concentrations were the highest at the end of monsoon.
      This study reveals that 62% of children in slum settlement were exposed to
      aflatoxin by the end of the third year of life. High aflatoxin exposure was
      detected at the end of rainy season and with the introduction of family food.
      These findings suggest interventions to ameliorate the problem of chronic
      aflatoxin exposure including childhood stunting.

PMID- 30185945
TI  - Development and validation of models to predict personal ventilation rate for air
      pollution research.
AB  - Air pollution intake represents the amount of pollution inhaled into the body and
      may be calculated by multiplying an individual's ventilation rate with the
      concentration of pollutant present in their breathing zone. Ventilation rate is
      difficult to measure directly, and methods for estimating ventilation rate (and
      intake) are lacking. Therefore, the goal of this work was to examine how well
      linear models using heart rate and other basic physiologic data can predict
      personal ventilation rate. We measured personal ventilation and heart rate among
      a panel of subjects (n = 36) while they conducted a series of specified routine
      tasks of varying exertion levels. From these data, 136 candidate models were
      identified using a series of variable transformation and selection algorithms. A
      second "free-living" validation study (n = 26) served as an independent
      validation dataset for these candidate models. The top-performing model, which
      included heart rate (Hr), resting heart rate (Hrest), age, sex, and hip
      circumference and interactions between sex with Hr, Hrest, age, and hip predicted
      ventilation rate (Ve) to within 11% and 33% for moderate (Ve = 45 L/min) and low
      (Ve = 15 L/min) intensity activities, respectively, based on the validation
      study. Many of the promising candidate models performed substantially worse under
      independent validation. Our results indicate that while measures of air pollution
      exposure and intake are highly correlated within tasks for a given individual,
      this correlation decreases substantially across tasks (i.e., as individuals go
      about a series of typical daily activities). This discordance between exposure
      and intake may influence exposure-response estimates in epidemiological studies.
      New air pollution studies should consider the trade-offs between the predictive
      ability of intake models and the error potentially introduced by not accounting
      for ventilation rate.

PMID- 30185946
TI  - Population dynamics based on mobile phone data to improve air pollution exposure
      assessments.
AB  - Air pollution is one of the greatest challenges cities are facing today and
      improving air quality is a pressing need to reduce negative health impacts. In
      order to efficiently evaluate which are the most appropriate policies to reduce
      the impact of urban pollution sources (such as road traffic), it is essential to
      conduct rigorous population exposure assessments. One of the main limitations
      associated with those studies is the lack of information about population
      distribution in the city along the day (population dynamics). The pervasive use
      of mobile devices in our daily lives opens new opportunities to gather large
      amounts of anonymized and passively collected geolocation data allowing the
      analysis of population activity and mobility patterns. This study presents a
      novel methodology to estimate population dynamics from mobile phone data based on
      a user-centric mobility model approach. The methodology was tested in the city of
      Madrid (Spain) to evaluate population exposure to NO2. A comparison with
      traditional census-based methods shows relevant discrepancies at disaggregated
      levels and highlights the need to incorporate mobility patterns into population
      exposure assessments.

PMID- 30185947
TI  - Epidemiology: a foundation of environmental decision making.
AB  - Many epidemiologic studies are designed so they can be drawn upon to provide
      scientific evidence for evaluating hazards of environmental exposures, conducting
      quantitative assessments of risk, and informing decisions designed to reduce or
      eliminate harmful exposures. However, experimental animal studies are often
      relied upon for environmental and public health policy making despite the
      expanding body of observational epidemiologic studies that could inform the
      relationship between actual, as opposed to controlled, exposures and health
      effects. This paper provides historical examples of how epidemiology has informed
      decisions at the U.S. Environmental Protection Agency, discusses some challenges
      with using epidemiology to inform decision making, and highlights advances in the
      field that may help address these challenges and further the use of epidemiologic
      studies moving forward.

PMID- 30185948
TI  - Pyrethroid levels in toddlers' breathing zone following a simulated indoor
      pesticide spray.
AB  - Application of pyrethroid insecticides in residential settings may result in
      children's exposures to these chemicals and possible adverse health effects.
      Household dust is a recognized reservoir for pyrethroids and a potential medium
      for multi-route pyrethroid exposure. Young children move and play in a manner
      that resuspends dust, and since their breathing zone is close to the floor, they
      will have higher inhalation exposure to pesticide-laden dust than other age
      groups. Directly measuring a toddler's exposure to household dust presents many
      logistic challenges. We simulated the dust resuspension induced by a toddler
      using a robot, which also served as a platform to collect air samples at the
      toddler's breathing zone height. We performed simulated pyrethroid residential
      spray and dust resuspension experiments on vinyl and carpeted floors. The mean
      pyrethroid airborne concentrations in the stationary and mobile samples were
      0.065 MUg/m3 and 0.143 MUg/m3 for the vinyl floor with 1 g/m2 dust loading, and
      0.034 MUg/m3 and 0.061 MUg/m3 for the carpeted floor with 10 g/m2 dust loading,
      respectively. Pyrethroids concentrations in the settled dust samples were
      significantly lower than that measured in the stationary and mobile samples in
      the carpeted floor experiments. Thus, the use of stationary samples and settled
      dust samples may underestimate a toddler's personal inhalation exposure to
      pyrethroids in residential houses.

PMID- 30185949
TI  - A comparison of genome cohort participants' genetic knowledge and preferences to
      receive genetic results before and after a genetics workshop.
AB  - Several biobanks have begun returning genetic results to individuals, making the
      development of public genetic literacy an urgent task for their effective use. No
      research exists regarding the effects of genetic education on biobank
      participants, so we conducted genetics workshops with specialists, and surveyed
      differences in the participants' (n = 112) preferences to receive their own
      genetic information by disease categories and their genetic knowledge using
      questionnaires before and after the workshops. Almost 90% of our participants
      were over 60 years old, which was similar to our previous preference research.
      The preference to receive five of the six categories of genetic information
      (lifestyle diseases, pharmacogenetics, adult-onset non-clinically actionable
      diseases, non-clinically actionable multifactorial diseases, and all genetic
      information) was slightly but significantly decreased after the genetics
      workshop. More participants preferred to receive genetic results regarding
      lifestyle diseases, pharmacogenetics, and adult-onset clinically actionable
      diseases after the workshop, while less participants preferred to receive
      information regarding adult-onset non-clinically actionable diseases, non
      clinically actionable multifactorial diseases, and all genetic information. Total
      genetic knowledge scores significantly increased after the workshop (before:
      11.89, after: 13.30, p < 0.001). Our findings suggest that genetics workshops are
      useful to improve the genetic literacy of genome cohort participants.

PMID- 30185950
TI  - Publisher Correction: Structural underpinnings of oestrogen receptor mutations in
      endocrine therapy resistance.
AB  - The originally published article contained an error in the legend of
      supplementary figure 1. A figure permission line was left off. The correct figure
      permission line has now been added to the HTML and PDF versions of the article,
      stating that "Data shown in (B) and (C) of this figure were originally published
      in Jeyakumar, M., Carlson, K. E., Gunther, J. R. & Katzenellenbogen, J. A.
      Exploration of dimensions of estrogen potency: parsing ligand binding and
      coactivator binding affinities. J. Biol. Chem. 286, 12971-12982, (2011) (c) the
      American Society for Biochemistry and Molecular Biology (Ref. 53)."

PMID- 30185952
TI  - Mitigation of hysteresis due to a pseudo-photochromic effect in thermochromic
      smart window coatings.
AB  - The aim of thermochromic window coatings is to reduce the energy consumption in
      the built environment by passively switching between a high solar transmitting
      state at low temperatures and low solar transmitting state at high temperatures.
      Previous studies have highlighted the negative impact of phase transition
      hysteresis on the performance of reflection based thermochromic films. However in
      the literature, the best reported results have depended on vanadium dioxide
      nanoparticle composites and anti-reflective structures that modulate light via
      changes in absorption rather than reflection. In light of these factors, this
      work aims to demonstrate theoretically, how the effects of phase transition
      hysteresis and gradient differ between absorbing and non-absorbing thermochromic
      films. To quantify and compare the performance of films with different transition
      characteristics, we define a metric based on the varying net energy flux through
      the window over the course of a year, including thermal energy re-radiated into
      the building from the film. Specifically, and importantly for the field, we
      demonstrate that a pseudo-photochromic effect in absorbing thermochromic films
      mitigates the detrimental effects of phase transition hysteresis and gradient
      that have been reported for reflection based thermochromic films. We find that
      for moderate hysteresis widths of 15  degrees C, the performance of the non
      absorbing case drops to ~60% of its initial value whilst the performance of the
      absorbing film only drops to ~95%. As a result we find that the absorbing case
      outperforms the non-absorbing case when hysteresis widths are greater than 8 
      degrees C.

PMID- 30185953
TI  - Diagnostics of Data-Driven Models: Uncertainty Quantification of PM7 Semi
      Empirical Quantum Chemical Method.
AB  - We report an evaluation of a semi-empirical quantum chemical method PM7 from the
      perspective of uncertainty quantification. Specifically, we apply Bound-to-Bound
      Data Collaboration, an uncertainty quantification framework, to characterize (a)
      variability of PM7 model parameter values consistent with the uncertainty in the
      training data and (b) uncertainty propagation from the training data to the model
      predictions. Experimental heats of formation of a homologous series of linear
      alkanes are used as the property of interest. The training data are chemically
      accurate, i.e., they have very low uncertainty by the standards of computational
      chemistry. The analysis does not find evidence of PM7 consistency with the entire
      data set considered as no single set of parameter values is found that captures
      the experimental uncertainties of all training data. A set of parameter values
      for PM7 was able to capture the training data within +/-1 kcal/mol, but not to
      the smaller level of uncertainty in the reported data. Nevertheless, PM7 was
      found to be consistent for subsets of the training data. In such cases,
      uncertainty propagation from the chemically accurate training data to the
      predicted values preserves error within bounds of chemical accuracy if
      predictions are made for the molecules of comparable size. Otherwise, the error
      grows linearly with the relative size of the molecules.

PMID- 30185951
TI  - Feature-dependent intrinsic functional connectivity across cortical depths in the
      human auditory cortex.
AB  - Frequency preference and spectral tuning are two cardinal features of information
      processing in the auditory cortex. However, sounds should not only be processed
      in separate frequency bands because information needs to be integrated to be
      meaningful. One way to better understand the integration of acoustic information
      is to examine the functional connectivity across cortical depths, as neurons are
      already connected differently across laminar layers. Using a tailored receiver
      array and surface-based cortical depth analysis, we revealed the frequency
      preference as well as tuning-width dependent intrinsic functional connectivity
      (iFC) across cortical depths in the human auditory cortex using functional
      magnetic resonance imaging (fMRI). We demonstrated feature-dependent iFC in both
      core and noncore regions at all cortical depths. The selectivity of frequency
      preference dependent iFC was higher at deeper depths than at intermediate and
      superficial depths in the core region. Both the selectivity of frequency
      preference and tuning-width dependent iFC were stronger in the core than in the
      noncore region at deep cortical depths. Taken together, our findings provide
      evidence for a cortical depth-specific feature-dependent functional connectivity
      in the human auditory cortex.

PMID- 30185954
TI  - Climate-induced changes in continental-scale soil macroporosity may intensify
      water cycle.
AB  - Soil macroporosity affects field-scale water-cycle processes, such as
      infiltration, nutrient transport and runoff1,2, that are important for the
      development of successful global strategies that address challenges of food
      security, water scarcity, human health and loss of biodiversity3. Macropores
      large pores that freely drain water under the influence of gravity-often
      represent less than 1 per cent of the soil volume, but can contribute more than
      70 per cent of the total soil water infiltration4, which greatly magnifies their
      influence on the regional and global water cycle. Although climate influences the
      development of macropores through soil-forming processes, the extent and rate of
      such development and its effect on the water cycle are currently unknown. Here we
      show that drier climates induce the formation of greater soil macroporosity than
      do more humid ones, and that such climate-induced changes occur over shorter
      timescales than have previously been considered-probably years to decades.
      Furthermore, we find that changes in the effective porosity, a proxy for
      macroporosity, predicted from mean annual precipitation at the end of the century
      would result in changes in saturated soil hydraulic conductivity ranging from -55
      to 34 per cent for five physiographic regions in the USA. Our results indicate
      that soil macroporosity may be altered rapidly in response to climate change and
      that associated continental-scale changes in soil hydraulic properties may set up
      unexplored feedbacks between climate and the land surface and thus intensify the
      water cycle.

PMID- 30185955
TI  - Synthetic three-dimensional atomic structures assembled atom by atom.
AB  - A great challenge in current quantum science and technology research is to
      realize artificial systems of a large number of individually controlled quantum
      bits for applications in quantum computing and quantum simulation. Many
      experimental platforms are being explored, including solid-state systems, such as
      superconducting circuits1 or quantum dots2, and atomic, molecular and optical
      systems, such as photons, trapped ions or neutral atoms3-7. The latter offer
      inherently identical qubits that are well decoupled from the environment and
      could provide synthetic structures scalable to hundreds of qubits or more8.
      Quantum-gas microscopes9 allow the realization of two-dimensional regular
      lattices of hundreds of atoms, and large, fully loaded arrays of about 50
      microtraps (or 'optical tweezers') with individual control are already available
      in one10 and two11 dimensions. Ultimately, however, accessing the third dimension
      while keeping single-atom control will be required, both for scaling to large
      numbers and for extending the range of models amenable to quantum simulation.
      Here we report the assembly of defect-free, arbitrarily shaped three-dimensional
      arrays, containing up to 72 single atoms. We use holographic methods and fast,
      programmable moving tweezers to arrange-atom by atom and plane by plane-initially
      disordered arrays into target structures of almost any geometry. These results
      present the prospect of quantum simulation with tens of qubits arbitrarily
      arranged in space and show that realizing systems of hundreds of individually
      controlled qubits is within reach using current technology.

PMID- 30185956
TI  - Sorting ultracold atoms in a three-dimensional optical lattice in a realization
      of Maxwell's demon.
AB  - In 1872, Maxwell proposed his famous 'demon' thought experiment1. By discerning
      which particles in a gas are hot and which are cold, and then performing a series
      of reversible actions, Maxwell's demon could rearrange the particles into a
      manifestly lower-entropy state. This apparent violation of the second law of
      thermodynamics was resolved by twentieth-century theoretical work2: the entropy
      of the Universe is often increased while gathering information3, and there is an
      unavoidable entropy increase associated with the demon's memory4. The appeal of
      the thought experiment has led many real experiments to be framed as demon-like.
      However, past experiments had no intermediate information storage5, yielded only
      a small change in the system entropy6,7 or involved systems of four or fewer
      particles8-10. Here we present an experiment that captures the full essence of
      Maxwell's thought experiment. We start with a randomly half-filled three
      dimensional optical lattice with about 60 atoms. We make the atoms sufficiently
      vibrationally cold so that the initial disorder is the dominant entropy. After
      determining where the atoms are, we execute a series of reversible operations to
      create a fully filled sublattice, which is a manifestly low-entropy state. Our
      sorting process lowers the total entropy of the system by a factor of 2.44. This
      highly filled ultracold array could be used as the starting point for a neutral
      atom quantum computer.

PMID- 30185957
TI  - A complex dynamo inferred from the hemispheric dichotomy of Jupiter's magnetic
      field.
AB  - The Juno spacecraft, which is in a polar orbit around Jupiter, is providing
      direct measurements of the planet's magnetic field close to its surface1. A
      recent analysis of observations of Jupiter's magnetic field from eight (of the
      first nine) Juno orbits has provided a spherical-harmonic reference model
      (JRM09)2 of Jupiter's magnetic field outside the planet. This model is of
      particular interest for understanding processes in Jupiter's magnetosphere, but
      to study the field within the planet and thus the dynamo mechanism that is
      responsible for generating Jupiter's main magnetic field, alternative models are
      preferred. Here we report maps of the magnetic field at a range of depths within
      Jupiter. We find that Jupiter's magnetic field is different from all other known
      planetary magnetic fields. Within Jupiter, most of the flux emerges from the
      dynamo region in a narrow band in the northern hemisphere, some of which returns
      through an intense, isolated flux patch near the equator. Elsewhere, the field is
      much weaker. The non-dipolar part of the field is confined almost entirely to the
      northern hemisphere, so there the field is strongly non-dipolar and in the
      southern hemisphere it is predominantly dipolar. We suggest that Jupiter's
      dynamo, unlike Earth's, does not operate in a thick, homogeneous shell, and we
      propose that this unexpected field morphology arises from radial variations,
      possibly including layering, in density or electrical conductivity, or both.

PMID- 30185958
TI  - Facing up to the global challenges of ageing.
AB  - Longer human lives have led to a global burden of late-life disease. However,
      some older people experience little ill health, a trait that should be extended
      to the general population. Interventions into lifestyle, including increased
      exercise and reduction in food intake and obesity, can help to maintain
      healthspan. Altered gut microbiota, removal of senescent cells, blood factors
      obtained from young individuals and drugs can all improve late-life health in
      animals. Application to humans will require better biomarkers of disease risk and
      responses to interventions, closer alignment of work in animals and humans, and
      increased use of electronic health records, biobank resources and cohort studies.

PMID- 30185959
TI  - Jupiter's magnetic field revealed by the Juno spacecraft.

PMID- 30185960
TI  - Designer atom arrays for quantum computing.

PMID- 30185962
TI  - The key to a happy lab life is in the manual.

PMID- 30185963
TI  - Evaluate power and bias in synthesizing evidence for policy.

PMID- 30185964
TI  - New York shark bites: DNA result should calm the waters.

PMID- 30185965
TI  - Gerrymandering: computers are impervious to power, users are not.

PMID- 30185966
TI  - European politicians must put greater trust in plant scientists.

PMID- 30185968
TI  - Reconstructing the retina.

PMID- 30185967
TI  - The quest to conquer Earth's space junk problem.

PMID- 30185969
TI  - Retinal repair: visions of the future.

PMID- 30185970
TI  - Failsafes.

PMID- 30185971
TI  - Devastating museum fire, silent Mars rover and financial disclosures.

PMID- 30185972
TI  - In Vitro Selection of Specific DNA Aptamers Against the Anti-Coagulant Dabigatran
      Etexilate.
AB  - Dabigatran Etexilate (PRADAXA) is a new oral anticoagulant increasingly used for
      a number of blood thrombosis conditions, prevention of strokes and systemic
      emboli among patients with atrial fibrillation. It provides safe and adequate
      anticoagulation for prevention and treatment of thrombus in several clinical
      settings. However, anticoagulation therapy can be associated with an increased
      risk of bleeding. There is a lack of specific laboratory tests to determine the
      level of this drug in blood. This is considered the most important obstacles of
      using this medication, particularly for patients with trauma, drug toxicity, in
      urgent need for surgical interventions or uncontrolled bleeding. In this work, we
      performed Systematic evolution of ligands by exponential enrichment (SELEX) to
      select specific DNA aptamers against dabigatran etexilate. Following multiple
      rounds of selection and enrichment with a randomized 60-mer DNA library, specific
      DNA aptamers for dabigatran were selected. We investigated the affinity and
      specificity of generated aptamers to the drug showing dissociation constants (Kd)
      ranging from 46.8-208 nM. The most sensitive aptamer sequence was selected and
      applied in an electrochemical biosensor to successfully achieve 0. 01 ng/ml level
      of detection of the target drug. With further improvement of the assay and
      optimization, these aptamers would replace conventional antibodies for developing
      detection assays in the near future.

PMID- 30185975
TI  - Gordon C. Hillman (1943-2018).

PMID- 30185973
TI  - Quantitative Proteomic Analysis of 2D and 3D Cultured Colorectal Cancer Cells:
      Profiling of Tankyrase Inhibitor XAV939-Induced Proteome.
AB  - Recently there has been a growing interest in three-dimensional (3D) cell culture
      systems for drug discovery and development. These 3D culture systems better
      represent the in vivo cellular environment compared to two-dimensional (2D) cell
      culture, thereby providing more physiologically reliable information on drug
      screening and testing. Here we present the quantitative profiling of a drug
      induced proteome in 2D- and 3D-cultured colorectal cancer SW480 cells using 2D
      nanoflow liquid chromatography-tandem mass spectrometry (2D-nLC-MS/MS) integrated
      with isobaric tags for relative and absolute quantitation (iTRAQ). We identified
      a total of 4854 shared proteins between 2D- and 3D-cultured SW480 cells and
      136/247 differentially expressed proteins (up/down-regulated in 3D compared to
      2D). These up/down-regulated proteins were mainly involved in energy metabolism,
      cell growth, and cell-cell interactions. We also investigated the XAV939
      (tankyrase inhibitor)-induced proteome to reveal factors involved in the 3D
      culture-selective growth inhibitory effect of XAV939 on SW480 cells. We
      identified novel XAV939-induced proteins, including gelsolin (a possible tumor
      suppressor) and lactate dehydrogenase A (a key enzyme of glycolysis), which were
      differentially expressed between 2D- and 3D-cultured SW480 cells. These results
      provide a promising informative protein dataset to determine the effect of XAV939
      on the expression levels of proteins involved in SW480 cell growth.

PMID- 30185976
TI  - Plants are intelligent; now what?

PMID- 30185974
TI  - Assessment of cerebral autoregulation using continuous-wave near-infrared
      spectroscopy during squat-stand maneuvers in subjects with symptoms of
      orthostatic intolerance.
AB  - Orthostatic lightheadedness in healthy young adults often leads to syncope in
      severe cases. One suggested underlying mechanism of orthostatic lightheadedness
      is a drop in transient blood pressure (BP); however, a decrease in BP does not
      always lead to a drop in cerebral blood flow (CBF) due to cerebral autoregulation
      (CA). We present a direct assessment method of CA using a multichannel continuous
      wave near-infrared spectroscopy (CW-NIRS) device that measures the temporal
      changes in oxy- and deoxy-hemoglobin concentrations in the prefrontal cortex.
      Twenty healthy young adults were recruited. During the experiment, continuous
      beat-to-beat BP and heart rate were simultaneously measured during repetitive
      squat-stand maneuvers. We introduce a new metric termed 'time-derivative
      hemodynamic model (DHbT)', which is the time-derivative of total-hemoglobin
      concentration change that reflects the changes of cerebral blood volume and CBF.
      Although the absolute levels and the variations of systolic and diastolic BPs and
      mean arterial pressure showed no significant difference between the two groups,
      the proposed model showed a distinct difference in slope variation and response
      time of DHbT between the subjects with frequent symptom of orthostatic
      intolerance and the healthy control subjects. Thus, these results clearly
      demonstrate the feasibility of using CW-NIRS devices as a CA performance
      assessment tool.

PMID- 30185977
TI  - Ready reckoning.

PMID- 30185978
TI  - Tethering the membranes.

PMID- 30185979
TI  - Slimy symbiosis.

PMID- 30185980
TI  - Foodie escapism.

PMID- 30185981
TI  - The birds, the bees and the bananas.

PMID- 30185982
TI  - Multiscale imaging of plant development by light-sheet fluorescence microscopy.
AB  - Light-sheet fluorescence microscopy (LSFM) methods collectively represent the
      major breakthrough in developmental bio-imaging of living multicellular
      organisms. They are becoming a mainstream approach through the development of
      both commercial and custom-made LSFM platforms that are adjusted to diverse
      biological applications. Based on high-speed acquisition rates under conditions
      of low light exposure and minimal photo-damage of the biological sample, these
      methods provide ideal means for long-term and in-depth data acquisition during
      organ imaging at single-cell resolution. The introduction of LSFM methods into
      biology extended our understanding of pattern formation and developmental
      progress of multicellular organisms from embryogenesis to adult body. Moreover,
      LSFM imaging allowed the dynamic visualization of biological processes under
      almost natural conditions. Here, we review the most important, recent biological
      applications of LSFM methods in developmental studies of established and emerging
      plant model species, together with up-to-date methods of data editing and
      evaluation for modelling of complex biological processes. Recent applications in
      animal models push LSFM into the forefront of current bio-imaging approaches.
      Since LSFM is now the single most effective method for fast imaging of
      multicellular organisms, allowing quantitative analyses of their long-term
      development, its broader use in plant developmental biology will likely bring new
      insights.

PMID- 30185983
TI  - Early shaping of a leaf.

PMID- 30185984
TI  - Reply to 'Early shaping of a leaf'.

PMID- 30185985
TI  - Origin of the catalytic activity of phosphorus doped MoS2 for oxygen reduction
      reaction (ORR) in alkaline solution: a theoretical study.
AB  - Phosphorus doped MoS2 nanosheets (P-doped MoS2) have been reported as excellent
      oxygen reduction reaction (ORR) catalysts with four-electron selectivity in
      alkaline solution. By performing density functional theory (DFT) calculations, we
      revealed the detailed reaction mechanism and the key reaction sites on surface of
      P-doped MoS2 for ORR catalysis. The double P-doped MoS2 (2P-MoS2) is calculated
      to be more stable than the single P-doped MoS2 (P-MoS2), and the configuration
      with two P atoms in neighboring sites exhibits the highest stability. The surface
      of P-doped MoS2 is found highly active for dissociation of O2. Comparative
      calculations reveal that P-MoS2 is unsuitable as ORR catalyst due to the high
      dissociation barrier of H2O (1.19 and 2.06 eV for the first and second adsorbed
      H2O), while the 2P-MoS2 shows good ORR catalytic activity with much lower
      dissociation barrier of H2O (0.62 eV). Furthermore, we elucidated that the ORR
      catalytic activity in 2P-MoS2 originates from the activated S2 atom, which
      provides an extra adsorption site for the first H2O and the following OH group
      benefited from the enhanced hydrogen bond interaction. Our results illustrate the
      mechanisms of doped MoS2 based catalysts and provide rational way for designing
      ORR catalysts with high activity.

PMID- 30185986
TI  - Addressing nonlinearities in Monte Carlo.
AB  - Monte Carlo is famous for accepting model extensions and model refinements up to
      infinite dimension. However, this powerful incremental design is based on a
      premise which has severely limited its application so far: a state-variable can
      only be recursively defined as a function of underlying state-variables if this
      function is linear. Here we show that this premise can be alleviated by
      projecting nonlinearities onto a polynomial basis and increasing the
      configuration space dimension. Considering phytoplankton growth in light-limited
      environments, radiative transfer in planetary atmospheres, electromagnetic
      scattering by particles, and concentrated solar power plant production, we prove
      the real-world usability of this advance in four test cases which were previously
      regarded as impracticable using Monte Carlo approaches. We also illustrate an
      outstanding feature of our method when applied to acute problems with interacting
      particles: handling rare events is now straightforward. Overall, our extension
      preserves the features that made the method popular: addressing nonlinearities
      does not compromise on model refinement or system complexity, and convergence
      rates remain independent of dimension.

PMID- 30185988
TI  - A Notch in the joint that exacerbates osteoarthritis.

PMID- 30185987
TI  - Gel with silver and ultrasmall iron oxide nanoparticles produced with Amanita
      muscaria extract: physicochemical characterization, microstructure analysis and
      anticancer properties.
AB  - Combination therapy remains one of the most promising and intensively developed
      direction in cancer treatment. This study is aimed to combine and investigate the
      anticancer properties of silver nanoparticles (NPs) and Amanita muscaria mushroom
      in gel formulation. For this, hyaluronic acid was used as gel-forming agent,
      whereas Amanita muscaria extract was used as capping agent during silver and
      ultrasmall iron oxide (MAg) NPs synthesis. Amanita muscaria compounds formed NP's
      surface layer and contributed anticancer properties, whereas silver NPs
      contributed anticancer, fluorescence and photoactive properties to the gel.
      Physicochemical characterization included X-ray diffraction (XRD), microscopies
      (SEM, cryo-SEM, TEM, confocal fluorescence), spectrofluorometric method,
      thermogravimetric analysis (TGA), dynamic light scattering (DLS) techniques,
      energy dispersive (EDS), Fourier transform infrared (FTIR) and ultraviolet
      visible (UV-Vis) spectroscopies, zeta-potential and rheological measurements.
      Microstructure analysis of hyaluronic acid/MAg NPs gel was performed by cryo-SEM
      technique. We showed that hyaluronic acid is a perfect gel-forming agent from
      both biomedical and technological points of view. It is well-mixed with MAg NPs
      forming stable gel formulation; high homogeneity of hyaluronic acid/MAg NPs gel
      was shown by SEM EDS elemental mapping. Microstructure of the gel was found to be
      highly ordered and consisted of domains from perforated parallel tubular
      structures. This finding expanded our understanding of gels and broke the
      stereotype of gel structure as chaotic network of fibers. Cytotoxicity studies
      performed on 2D and 3D HeLa cell cultures pointed to a high potential of
      hyaluronic acid/MAg NPs gel for local treatment of cancer. Cell response was
      found to be significantly different for 2D and 3D cell cultures that was related
      to their different cytoarhitecture and gene expression. Thus, the results of the
      cellular spheroids viability showed that they were significantly more resistant
      to the cytotoxic action of MAg NPs and their gel formulation than 2D cell
      culture. Hyaluronic acid used as gelling agent in gel formulation was found to
      increase an effectiveness of active components (MAg NPs, Amanita muscaria
      extract) probably improving their transport inside HeLa spheroids.

PMID- 30185989
TI  - Time-dependent molecular emission in IRC+10216.
AB  - Context: The variability in IRC+10216, the envelope of the asymptotic giant
      branch (AGB) star CW Leo, has attracted increasing attention in recent years.
      Studying the details of this variability in the molecular emission required a
      systematic observation program. Aims: We aim to reveal and characterize the
      periodical variability of the rotational lines from several molecules and
      radicals in IRC+10216, and to compare it with previously reported IR variability.
      Methods: We carried out systematic monitoring within the ~80 to 116 GHz frequency
      range with the IRAM 30m telescope. Results: We report on the periodical
      variability in IRC+10216 of several rotational lines from the following molecules
      and radicals: HC3N, HC5N, CCH, C4H, C5H, and CN. The analysis of the variable
      molecular lines provides periods that are consistent with previously reported IR
      variability, and interesting phase lags are revealed that point toward radiative
      transfer and pumping, rather than chemical effects. Conclusions: This study
      indicates that observations of several lines of a given molecule have to be
      performed simultaneously or at least at the same phase in order to avoid
      erroneous interpretation of the data. In particular, merging ALMA data from
      different epochs may prove to be difficult, as shown by the example of the
      variability we studied here. Moreover, radiative transfer codes have to
      incorporate the effect of population variability in the rotational levels in CW
      Leo.

PMID- 30185990
TI  - Structure of photodissociation fronts in star-forming regions revealed by
      observations of high-J CO emission lines with Herschel.
AB  - Context: In bright photodissociation regions (PDRs) associated to massive star
      formation, the presence of dense "clumps" that are immersed in a less dense
      interclump medium is often proposed to explain the difficulty of models to
      account for the observed gas emission in high-excitation lines. Aims: We aim at
      presenting a comprehensive view of the modeling of the CO rotational ladder in
      PDRs, including the high-J lines that trace warm molecular gas at PDR interfaces.
      Methods: We observed the 12CO and 13CO ladders in two prototypical PDRs, the
      Orion Bar and NGC 7023 NW using the instruments onboard Herschel. We also
      considered line emission from key species in the gas cooling of PDRs (C+, O, H2)
      and other tracers of PDR edges such as OH and CH+. All the intensities are
      collected from Herschel observations, the literature and the Spitzer archive and
      are analyzed using the Meudon PDR code. Results: A grid of models was run to
      explore the parameter space of only two parameters: thermal gas pressure and a
      global scaling factor that corrects for approximations in the assumed geometry.
      We conclude that the emission in the high-J CO lines, which were observed up to J
      up =23 in the Orion Bar (J up =19 in NGC 7023), can only originate from small
      structures of typical thickness of a few 10-3 pc and at high thermal pressures
      (Pth ~ 108 K cm-3). Conclusions: Compiling data from the literature, we found
      that the gas thermal pressure increases with the intensity of the UV radiation
      field given by G0, following a trend in line with recent simulations of the
      photoevaporation of illuminated edges of molecular clouds. This relation can help
      rationalising the analysis of high-J CO emission in massive star formation and
      provides an observational constraint for models that study stellar feedback on
      molecular clouds.

PMID- 30185991
TI  - The chemistry of disks around T Tauri and Herbig Ae/Be stars.
AB  - Context: Infrared and (sub-)mm observations of disks around T Tauri and Herbig
      Ae/Be stars point to a chemical differentiation between both types of disks, with
      a lower detection rate of molecules in disks around hotter stars. Aims: To
      investigate the underlying causes of the chemical differentiation indicated by
      observations we perform a comparative study of the chemistry of T Tauri and
      Herbig Ae/Be disks. This is one of the first studies to compare chemistry in the
      outer regions of these two types of disks. Methods: We developed a model to
      compute the chemical composition of a generic protoplanetary disk, with
      particular attention to the photochemistry, and applied it to a T Tauri and a
      Herbig Ae/Be disk. We compiled cross sections and computed photodissociation and
      photoionization rates at each location in the disk by solving the FUV radiative
      transfer in a 1+1D approach using the Meudon PDR code and adopting observed
      stellar spectra. Results: The warmer disk temperatures and higher ultraviolet
      flux of Herbig stars compared to T Tauri stars induce some differences in the
      disk chemistry. In the hot inner regions, H2O, and simple organic molecules like
      C2H2, HCN, and CH4 are predicted to be very abundant in T Tauri disks and even
      more in Herbig Ae/Be disks, in contrast with infrared observations that find a
      much lower detection rate of water and simple organics toward disks around hotter
      stars. In the outer regions, the model indicates that the molecules typically
      observed in disks, like HCN, CN, C2H, H2CO, CS, SO, and HCO+, do not have drastic
      abundance differences between T Tauri and Herbig Ae disks. Some species produced
      under the action of photochemistry, like C2H and CN, are predicted to have
      slightly lower abundances around Herbig Ae stars due to a narrowing of the
      photochemically active layer. Observations indeed suggest that these radicals are
      somewhat less abundant in Herbig Ae disks, although in any case the inferred
      abundance differences are small, of a factor of a few at most. A clear chemical
      differentiation between both types of disks concerns ices. Owing to the warmer
      temperatures of Herbig Ae disks, one expects snowlines lying farther away from
      the star and a lower mass of ices compared to T Tauri disks. Conclusions: The
      global chemical behavior of T Tauri and Herbig Ae/Be disks is quite similar. The
      main differences are driven by the warmer temperatures of the latter, which
      result in a larger reservoir or water and simple organics in the inner regions
      and a lower mass of ices in the outer disk.

PMID- 30185992
TI  - Binarity and Accretion in AGB Stars: HST/STIS Observations of UV Flickering in Y
      Gem.
AB  - Binarity is believed to dramatically affect the history and geometry of mass loss
      in AGB and post-AGB stars, but observational evidence of binarity is sorely
      lacking. As part of a project to search for hot binary companions to cool AGB
      stars using the GALEX archive, we discovered a late-M star, Y Gem, to be a source
      of strong and variable UV and X-ray emission. Here we report UV spectroscopic
      observations of Y Gem obtained with the Hubble Space Telescope that show strong
      flickering in the UV continuum on time-scales of ? 20 s, characteristic of an
      active accretion disk. Several UV lines with P-Cygni-type profiles from species
      such as Si IV and C IV are also observed, with emission and absorption features
      that are red- and blue-shifted by velocities of ~500 km s-1 from the systemic
      velocity. Our model for these (and previous) observations is that material from
      the primary star is gravitationally captured by a companion, producing a hot
      accretion disk. The latter powers a fast outflow that produces blue-shifted
      features due to absorption of UV continuum emited by the disk, whereas the red
      shifted emission features arise in heated infalling material from the primary.
      The outflow velocities support a previous inference by Sahai et al. (2015) that Y
      Gem's companion is a low-mass main-sequence star. Blackbody fitting of the UV
      continuum implies an accretion luminosity of about 13 L?, and thus a mass
      accretion rate > 5 * 10-7M? yr-1; we infer that Roche lobe overflow is the most
      likely binary accretion mode for Y Gem.

PMID- 30185993
TI  - Stability of CH3NCO in astronomical ices under energetic processing. A laboratory
      study.
AB  - Methyl isocyanate (CH3NCO) was recently found in hot cores and suggested on comet
      67P/CG. The incorporation of this molecule into astrochemical networks requires
      data on its formation and destruction. In this work, ices of pure CH3NCO and of
      CH3NCO(4-5%)/H2O mixtures deposited at 20 K were irradiated with a UV D2 lamp
      (120-400 nm) and bombarded by 5 keV electrons to mimic the secondary electrons
      produced by cosmic rays (CRs). The destruction of CH3NCO was studied using IR
      spectroscopy. After processing, the nua-NCO band of CH3NCO disappeared and IR
      bands corresponding to CO, CO2, OCN- and HCN/CN- appeared instead. The products
      of photon and electron processing were very similar. Destruction cross sections
      and half-life doses were derived from the measurements. Water ice provides a good
      shield against UV irradiation (half-life dose of ~ 64 eV molecule-1 for CH3NCO in
      water-ice), but not so good against high-energy electrons (half-life dose ~ 18 eV
      molecule-1). It was also found that CH3NCO does not react with H2O over the 20
      200 K temperature range. These results indicate that hypothetical CH3NCO in the
      ices of dense clouds should be stable against UV photons and relatively stable
      against CRs over the lifetime of a cloud (~ 107 yr), and could sublime in the hot
      core phase. On the surface of a Kuiper belt object (the original location of
      comet 67P/CG) the molecule would be swiftly destroyed, both by photons and CRs,
      but embedded below just 10 MUm of water-ice, the molecule could survive for ~ 109
      yr.

PMID- 30185994
TI  - Adverse Drug Reaction Reporting: Opportunities to Increase Pharmacists' Role.

PMID- 30185995
TI  - ?

PMID- 30185996
TI  - Impact of a Policy Change on Pharmacists' Reporting of Adverse Drug Reactions.
AB  - Background: Spontaneous reports of adverse drug reactions (ADRs) form an
      essential component of both drug safety monitoring and patient safety
      initiatives. Pharmacists are well positioned to report ADRs, but many barriers
      exist to their doing so. Over the past decade, substantial changes have occurred
      with regard to drug regulations and medication safety initiatives, and it is
      possible that knowledge-based interventions may be needed to enhance ADR
      reporting by pharmacists. Objective: To determine whether ADR reporting
      behaviours of pharmacists improved after release of a revised policy on the
      reporting of medication incidents. Methods: A telephone survey was administered
      to pharmacists practising in the Canadian Forces Health Services Group. Self
      reported behaviours and perceived barriers related to ADR reporting were compared
      before and 3 months after the updated policy was released. Accuracy in
      participants' self-assessed ADR reporting was evaluated using independently
      derived workload statistics. Results: During the second survey phase (after
      release of the revised policy), a greater proportion of respondents reported
      awareness of institutional policies on ADR reporting and declared that they were
      able to complete all necessary ADR reports during their assigned work hours.
      However, the number of ADR reports submitted did not increase. Participants'
      recall of their ADR reporting behaviour was corroborated by workload data. During
      the second survey phase, there was a noticeable reduction in the number of free
      form comments mentioning lack of staff as a barrier to ADR reporting.
      Conclusions: Release of a more comprehensive policy was not associated with an
      increase in the number of ADR reports generated by pharmacists in the study
      setting. Interventions to strengthen the organization's work processes for
      detection of ADRs and submission of individual ADR reports should be strongly
      considered, to reinforce and enhance existing ADR reporting behaviours among
      pharmacists.

PMID- 30185997
TI  - Antimicrobial Use at Acute Care Hospitals in Nova Scotia: A Point Prevalence
      Survey.
AB  - Background: Point prevalence surveys are used to monitor antimicrobial use and
      identify targets for improvement through antimicrobial stewardship activities.
      Few studies have evaluated antimicrobial use in Nova Scotia acute care
      institutions. Objectives: To determine the prevalence and characteristics of
      antimicrobial use in Nova Scotia hospitals. Methods: A point prevalence survey
      was conducted between June and November 2015 for patients admitted to hospitals
      with at least 30 acute care beds. On each survey day, charts were reviewed to
      identify patients receiving antimicrobial agents on that day. Data were gathered
      on the type of antimicrobial agent prescribed, route of administration, intended
      duration of use, and indication. Adherence to regional and local treatment
      guidelines was assessed. Results were summarized descriptively. Findings were
      compared using the Fisher exact test or the Cochran-Armitage trend test. Results:
      Twelve of the 13 eligible hospitals participated, and a total of 1499 patient
      charts were examined. The overall prevalence of antimicrobial use was 30.6%
      (458/1499). The prevalence of antimicrobial use differed significantly according
      to area of specialty, with the highest prevalence occurring in intensive care
      wards (47.2%, 50/106) and surgical wards (43.4%, 179/412), as compared with
      medical wards (27.9%, 192/687) and "other" specialty wards (11.1%, 32/289) (p <
      0.001). Among the 520 indications for antimicrobial use, the most common was
      respiratory tract infection (81 or 15.6%). In total, 660 antimicrobial agents
      were prescribed to the 458 patients; a third of these patients (152 or 33.2%)
      received more than 1 antimicrobial agent. The class of antimicrobials most
      frequently prescribed was "other beta-lactam antimicrobials" (31.2%, 206/660).
      The majority of antimicrobials (62.0%, 409/660) were prescribed for
      administration via the parenteral route. Adherence to regional treatment
      guidelines was 29.9% (26 of 87 indications analyzed). Documentation of indication
      was lacking for 104 (20.0%) of the 520 indications, and documentation of the
      intended duration of antimicrobial use was lacking for 326 (62.7%) of the 520
      indications. Conclusions: Antimicrobial agents were prescribed for about one
      third of acute care patients in Nova Scotia. Specific targets for improvement in
      antimicrobial use include decreases in prescribing of broad-spectrum and
      parenteral antimicrobials, better adherence to guidelines, and improved
      documentation. In developing initiatives, antimicrobial stewardship programs in
      Nova Scotia should focus on identified targets for improvement.

PMID- 30185998
TI  - Development of Pictograms to Enhance Medication Safety Practices of Health Care
      Workers and International Preferences.
AB  - Background: A panel of medication management experts previously identified 9 key
      medication safety issues and high-alert drug classes as representing the most
      pressing medication-handling issues in health care. Objective: To develop
      medication safety pictograms depicting medication safety issues and high-alert
      drug classes that represent medication-handling risks for health care personnel.
      Methods: An iterative design process, including activities such as semiotic
      analysis, design/redesign, and evaluation, was used to develop medication safety
      pictograms. Nurses, physicians, pharmacists, and students listed and drew graphic
      elements to depict each of the 9 key medication safety issues. Graduate students
      in graphic design developed the preliminary pictograms for the study. A Delphi
      survey was then conducted with experts recruited from the International
      Pharmaceutical Federation to reach consensus on the pictograms and provide
      feedback to the graphic designers. Health care providers from around the world
      were invited to participate in a survey to determine a preferred pictogram for
      each safety warning. Results: For each medication safety issue, 3 to 5 pictograms
      were developed on the basis of graphic elements suggested by 52 health care
      providers. These pictograms were then presented to 58 experts in 2 rounds of a
      Delphi process. For each medication safety issue, consensus on the 2 best
      pictograms was reached and feedback provided. A total of 799 participants from 61
      countries responded to the international preference survey. Most of the
      participants (n = 536, 67.1%) were Canadian, and of those, 385 (71.8%) were
      pharmacists. In 8 categories, consensus on the preferred pictogram was reached
      across the health care professions; however, a difference in preference was
      apparent for the pictogram representing "neuromuscular blocking agent", with
      nurses' preferred pictogram differing from the preference of other participants.
      Conclusion: This project produced pictograms to illustrate 9 important medication
      safety issues, which can now be validated through comprehension and recall
      assessments. Further study can also determine their potential to reduce
      medication administration errors.

PMID- 30185999
TI  - Validation of Pictograms for Safer Handling of Medications: Comprehension and
      Recall among Pharmacy Students.
AB  - Background: Medication preparation and administration are higher-risk steps in
      the medication management process. Therefore, medication management strategies,
      such as warnings and education about medication safety, are essential in
      preventing errors and improving the safe handling of medications by health care
      workers. Objectives: To validate comprehension of 9 pictograms designed to
      improve medication safety, and to assess long-term recall of these pictograms in
      a sample of pharmacy students. Methods: First- and second-year pharmacy students
      were recruited as participants. The study was divided into 2 phases:
      comprehension (Phase 1) and long-term recall (Phase 2). In Phase 1, a slideshow
      of the 9 pictograms was presented to participants, who were asked to write the
      meaning of and required action for each pictogram. The intended meaning of each
      pictogram was then presented to the participants. Four weeks later, long-term
      recall was assessed in Phase 2 of the study using the same method. The meaning
      and required action that participants provided for each pictogram were reviewed
      by 3 independent raters. A pictogram was considered to be validated in the
      pharmacy student population if at least 67% of participants identified the
      correct meaning or required action during the recall phase. Results: A total of
      101 pharmacy students participated in Phase 1 and 67 in Phase 2. In Phase 1, 4
      pictograms met the 67% threshold for comprehension. In Phase 2, after training, 7
      of the 9 pictograms were validated. Conclusions: Given the results obtained with
      pharmacy students, redesign may be necessary for 2 of the pictograms. The use of
      validated medication safety pictograms on medication labels and other identifiers
      may prevent errors during medication handling and administration; this is an
      important avenue of investigation for future studies.

PMID- 30186000
TI  - Inappropriate Prescription of Proton Pump Inhibitors in a Community Setting.
AB  - Background: Proton pump inhibitors (PPIs) are widely prescribed for
      gastrointestinal conditions, such as gastroesophageal reflux disease and
      dyspepsia, and for prevention of gastric ulcer. Although previous reports have
      described inappropriate prescription of PPIs in the hospital setting, data from
      the community are lacking. Objective: To assess PPI prescriptions in the
      ambulatory setting. Methods: Patients presenting to the emergency department of a
      teaching hospital between June 2016 and March 2017 were prospectively assessed
      for use of a PPI at home. The appropriateness of PPI prescription was evaluated
      on the basis of an interview with the patient and review of the medical record.
      The indication for PPI therapy was verified against current guidelines for the
      province of Quebec. Results: Over the 9-month study period, 2417 patients were
      screened, of whom 871 were included in the study. In relation to the Quebec
      guidelines, PPI prescription was inappropriate for 267 (30.7%) of the patients.
      When prescription of PPI for ulcer prevention in certain groups of patients (age
      >= 65 years and using acetylsalicylic acid or platelet aggregation inhibitors;
      age >= 75 years and using celecoxib) was re-classified as appropriate, the
      proportion of inappropriate PPI prescriptions declined to 20.3% (177/871).
      Conclusions: These findings suggest that inappropriate prescribing of PPIs
      remains problematic in the community setting in the province of Quebec.

PMID- 30186001
TI  - Successful Treatment of Stevens-Johnson Syndrome with Cyclosporine and
      Corticosteroid.

PMID- 30186002
TI  - Identifying Drug Interactions between Enzalutamide and Complementary Alternative
      Medications in a Patient with Metastatic Prostate Cancer: A Case Report.

PMID- 30186003
TI  - Should All Patients with Type 2 Diabetes Mellitus and Cardiovascular Disease
      Receive an SGLT2 Inhibitor?

PMID- 30186004
TI  - ?

PMID- 30186005
TI  - Are You Realizing the Full Potential of Pharmacy Practice in the Healthcare
      System?

PMID- 30186007
TI  - Development a Reverse Triage System Based on Modified Sequential Organ Failure
      Assessment for Increasing the Critical Care Surge Capacity.
AB  - Context: The capacity completeness are one of the serious problems in the bed's
      managements of the critical care units in a crisis and disaster situation.
      Reverse triage can help to hospital surge capacity in this situations. Aims: The
      aim of this study was to develop a reverse triage system based on Modified
      Sequential Organ Failure Assessment (MSOFA) for increasing critical care surge
      capacity. Settings and Design: This study was a prospective design that performed
      on the medical patients in critical care unit. Subjects and Methods: The MSOFA
      score for each patient was calculated in admission time and be continued until
      discharging time from critical care unit. Statistical Analysis Used: The Cox
      regression method was used to determine the relative risk values. At last, the
      patients were divided into three levels for reverse triage. Results: Four hundred
      and twenty patients were participated in this study. The mean of patients' MSOFA
      scores in the 1st day of admission in Critical Care was 5.40 +/- 3.8. The
      relative risk of internal patients discharge from critical care was (8.2%). Death
      relative risks were <25%, higher than 70% and between 25.1% and 69.9% for three
      color level of green, black, and red, respectively. Conclusion: The MSOFA scores
      can contribute to the design a leveling system for discharging patients from
      critical care unit. Based on this system, the members of the caring team can
      predict the final health status of the patient.

PMID- 30186006
TI  - Correlation of Neutrophil CD64 with Clinical Profile and Outcome of Sepsis
      Patients during Intensive Care Unit Stay.
AB  - Introduction: Neutrophil CD64 (nCD64) has been found to identify sepsis from
      nonseptic patients. It is also reported to be a predictor of survival and
      severity of sepsis. The goal of this study was to correlate serial nCD64 with
      Intensive Care Unit (ICU) outcome and severity of sepsis. Materials and Methods:
      A prospective observational study was conducted in 12-bedded critical care unit
      of a tertiary care center. Adult patients with sepsis were included in this
      study. Demographics, illness severity scores, clinical parameters, laboratory
      data, and 28-day outcome were recorded. Serial nCD64 analysis was done (on days
      0, 4, and 8) in consecutive patients. Results: Fifty-one consecutive patients
      were included in the study. Median Acute Physiology and Chronic Health Evaluation
      II was 16 (12-20) and mean Sequential Organ Failure Assessment was 9 (8-10).
      Compared to survivors, nonsurvivors had higher nCD64 on day 8 (P = 0.001). nCD64
      was higher in the septic shock group compared to sepsis group on days 0 and 8 (P
      < 0.05). Survivors showed improving trend of nCD64 over time while nonsurvivors
      did not. This trend was similar in the presence or absence of septic shock. nCD64
      count was a good predictor of the septic shock on day 0 (area under the curve
      [AUC] = 0.747, P = 0.010) and moderate predictor at day 8 (AUC = 0.679, P =
      0.028). Conclusion: Monitoring serial nCD64 during ICU stay may be helpful in
      determining the clinical course of septic patients.

PMID- 30186008
TI  - What Happens to Patients Discharged Against Medical Advice?
AB  - Introduction: Discharge against medical advice (DAMA) when requested by family
      members of patients in Indian Critical Care Units (CCUs) leads to loss of follow
      up and unknown patient outcomes. Exclusion of these patients from research
      analysis and quality audits confounds these results. We hence explored the
      proportion of patients leaving DAMA, reasons, and their outcomes at 30 and 90
      days. Methods: This was a prospective study of CCU patients admitted from July
      2013 to February 2014. All patients, who were DAMA during this period, were
      included in this study. Demographics, APACHE data, and outcomes were collected
      and compared to patients discharged regularly during the same period. Outcomes of
      DAMA patients at 30 and 90 days were gathered by telephone follow-up. Results:
      Among the 663 patients admitted to the CCU, 15.1% (100 patients) were DAMA. The
      baseline APACHE score of the DAMA group was higher than the regular discharge
      group (29.5 +/- 8.6 vs. 26.1 +/- 10.3; P = 0.002). During the 30-day follow-up,
      23% were alive, 56% dead, and 21% could not be contacted. At 90 days, mortality
      was 62% and survivors decreased to 14%. Common reasons for DAMA were - wanting to
      take the patient to another hospital (21%), reluctance for further treatments
      (12%), financial constraints (9%), and overall poor prognosis (7%). Conclusion: A
      significant proportion of patients in the CCU get DAMA despite high severity of
      illness. Understanding the outcomes of these patients will help refine CCU
      quality audit reports and research study results.

PMID- 30186009
TI  - The Platelet Count and its Implications in Sickle Cell Disease Patients Admitted
      for Intensive Care.
AB  - Background and Aims: In sickle cell disease (SCD) patients admitted for intensive
      care, evaluation of platelet counts in different types of sickle cell
      complications and its prognostic relevance are not well-studied. Illuminating
      these aspects were the objectives of this study. Materials and Methods: A chart
      review of 136 adult SCD patients consecutively admitted to our Intensive Care
      Unit (ICU) was done. The prognosis on day 1 was assessed by Acute Physiology and
      Chronic Health Evaluation (APACHE II) and multiple organ dysfunction scores
      (MODS). Receiver operating characteristic (ROC) curves evaluated the ability of
      platelet counts, MODS, and APACHE II scores to predict survival. Results: The
      most common types of crises were severe pain (n = 53), acute chest syndrome (n =
      40), and infection (n = 18); 17 patients were nonsurvivors. Platelet counts
      varied widely (range, 19-838 * 109/L) with thrombocytopenia (n = 30) and
      thrombocytosis (n = 11). Counts correlated directly with leukocytes and
      reticulocytes; inversely with lactate dehydrogenase, APACHE, and MODS scores.
      Areas under ROC curve for platelets, MODS, and APACHE scores to predict survival
      were 0.73, 0.85, and 0.93, respectively. Conclusions: In severe sickle cell
      crisis thrombocytopenia is more common than thrombocytosis. In the ICU, day 1
      platelet counts correlate inversely with prognostic scores and are significantly
      reduced in multi-organ failure and nonsurvivors. A platelet count above 175 *
      109/L predicts patient survival with high specificity and positive predictive
      value but lacks sensitivity.

PMID- 30186010
TI  - Retrospective Evaluation of Patients Who Leave against Medical Advice in a
      Tertiary Teaching Care Institute.
AB  - Context: Discharge against medical advice or leave against medical advice (DAMA
      or LAMA) is a global phenomenon. The magnitude of LAMA phenomenon has a wide
      geographical variation. LAMA reasons are an area of concern for all involved in
      health-care delivery system. Aims and Objectives: The study aimed to evaluate
      cases of LAMA retrospectively in a tertiary teaching care institute (1) to find
      the magnitude of LAMA cases (2) to evaluate demographic and patient
      characteristics of these cases. Subjects and Methods: We screened hospital record
      of a referral institute over 1 year after approval from IEC and ICMR, New Delhi.
      Patient demographics and disease characteristics were noted and statistically
      analyzed after compilation. Results: A total of 47,583 patients were admitted in
      the year 2015 through emergency and outpatient department. One thousand five
      hundred and fifty-six (3.3%) patients got DAMA. The mean age of patient excluding
      infants was 46.64 +/- 20.55 years. There were 62.9% of males. Average hospital
      stay of these cases was 4.09 +/- 4.39 days. Most of the patients (70%) belonged
      to medical specialties and had longer stay as compared to surgical specialties.
      Most of LAMA patients were suffering from infections, trauma, and malignancies.
      Most of the patients had LAMA from ward (62%) followed by Intensive Care Unit
      (ICU) (28.8%) and emergency (9.2%). In 592 (38%) of LAMA patients, the reason for
      leaving was not clear. The common cited reasons for LAMA were financial (27.6%)
      and poor prognosis (20.5%). Conclusions: About 3.3% of patients left hospital
      against medical advice in our retrospective analysis. Most of these cases did so
      from ward followed by ICU. Financial reasons and expected poor outcome played a
      significant role.

PMID- 30186011
TI  - A Prospective Study of Fungal Colonization and Invasive Fungal Disease in Long
      Term Mechanically Ventilated Patients in a Respiratory Intensive Care Unit.
AB  - Background: Long-term mechanical ventilation in an Intensive Care Unit (ICU)
      exposes the patient to fungal colonization and invasive fungal disease due to the
      presence of indwelling catheters, administration of broad-spectrum antibiotics,
      and intravenous corticosteroids. A study is hence required to study the risk
      factors and incidence of fungal infection in these patients. Methods: A
      prospective observational study was carried out in the respiratory ICU of a
      tertiary care hospital for a period of approximately 1 year in which patients on
      mechanical ventilation (>7 days) were enrolled. Blood, urine, and endotracheal
      aspirate (ETA) of these patients were sent for fungal culture on day 1 and day 7
      of mechanical ventilation. Fiberoptic bronchoscopy was done on day 7 and
      bronchoalveolar lavage along with transbronchial lung biopsy (TBLB) were sent for
      fungal culture. Results: During 7 days of ventilation, there was a statistically
      significant increase in the proportion of culture-positive ETA and urine samples.
      Overall, Candida albicans emerged as the most common colonizer. Blood candidemia
      was seen in 10% of patients on day 7 of mechanical ventilation. Fungal invasion
      of the lung, as evidenced by fungal culture-positive TBLB specimens, was seen in
      17% of patients. Diabetes was found to be a statistically significant risk factor
      for respiratory and urinary tract colonization as well as invasive fungal
      disease. Conclusion: Long-term mechanical ventilation (>7 days) is strongly
      associated with fungal colonization of the respiratory tract and urinary tract.
      Appropriate prophylactic antifungals may be given and infection control practices
      to be observed to ensure minimum colonization and therefore infection in such
      settings.

PMID- 30186012
TI  - Role of Intra-abdominal Pressure in Early Acute Kidney Injury: A Prospective
      Cohort Study in Critically Ill Obstetric Patients.
AB  - Aims: This prospective cohort study evaluated intra-abdominal pressure (IAP) and
      its role in causing acute kidney injury (AKI) in critically ill obstetric
      patients and utility of urinary neutrophil gelatinase-associated lipocalin (NGAL)
      to predict AKI. Methods: A total of 50 eligible obstetric patients admitted to
      our Intensive Care Unit were enrolled and daily IAP measured using indwelling
      Foley catheter. Early AKI was diagnosed as per the KDIGO criteria and urine
      assessed for NGAL using ELISA. Results: AKI was seen in 54% and intra-abdominal
      hypertension (IAH) in 21% patients. In patients with and without AKI, there was
      statistically similar IAP on day 1 (P = 0.542) and day 2 (P = 0.907) as well as
      incidence of IAH (19% vs. 23%) (P = 0.766). Area under receiver operating
      characteristic curve (AUC) for IAP to predict early AKI was 0.499 (95% confidence
      interval [CI]: 0.325-0.673) (P = 0.992). Urinary NGAL concentration was
      significantly greater in patients with early AKI compared to those without (P =
      0.006); AUC for urinary NGAL to detect early AKI was 0.734 (95% CI: 0.583-0.884)
      (P = 0.006) and optimal cutoff was 53.7 ng/ml. Conclusions: IAH and AKI are
      common in critically ill obstetric patients. While IAP does not correlate with
      early AKI, NGAL is useful to predict AKI.

PMID- 30186013
TI  - A Hot Body in a Cold Room Hyperthermia Secondary to Rapid Diuresis in Cardiac
      Failure; the Perils of Rapid Fluid Shifts.
AB  - A 66-year-old man was admitted with anasarca and congestive cardiac failure. He
      was started on intravenous diuretics and fluid restriction and lost nearly 35 kg
      of fluids in 13 days. He then developed hyperthermia and delirium. An extensive
      workup was inconclusive. Analysis of his inpatient fluid balance chart revealed
      the chance association of massive fluid loss and hyperthermia. Rapid diuresis
      induced hyperthermia and volume contraction were considered, and his fluid
      balance was adjusted. Within 2 days, his temperature normalized and he regained
      consciousness. Hyperthermia and its causative mechanism are discussed in this
      article.

PMID- 30186014
TI  - Acute Reversible Ischemic Stroke after Snake Bite.
AB  - Snake bite is very common in India. Ischemic stroke after snake bite has been
      described in the literature sparsely. Furthermore, the onset of stroke and its
      clinical reversibility is a rarity. Here, we present a case of snake bite with
      ischemic stroke which has clinically reversible outcome.

PMID- 30186015
TI  - Acute Suppurative Thyroiditis with Thyroid Abscess by Klebsiella pneumoniae: An
      Unusual Presentation.
AB  - Acute suppurative thyroiditis with thyroid abscess is very uncommon cause of
      thyroiditis. Thyroid infection in a diabetic patient is commonly labeled to the
      relative immunosuppressive state of diabetes mellitus. We present a case of a
      diabetic patient showing clinical symptoms of acute thyroiditis with progressing
      dysphagia, who was diagnosed as thyroid abscess as a result of Klebsiella
      pneumoniae. The infection in the absence of other significant history was
      initially considered de novo; however, on extensive evaluation was associated
      with other distant primary source of the same microbe. The patient was managed
      with minimally invasive drainage of abscess and intravenous antibiotics.

PMID- 30186016
TI  - Severe Adult-Onset Still's Disease Mimicking Systemic Infection.
AB  - Adult-onset Still's disease (AOSD) is an uncommon entity that can mimic
      infection. Patients present with fever for more than 1-week, joint pain, and
      rash. We report a case of 22-year-old male who presented with fever, sore throat,
      and abdominal pain. During hospitalization, he had multiple episodes of
      tachycardia and tachypnea requiring mechanical ventilation. The patient had
      elevated white blood cell count, procalcitonin, and troponin. He was extensively
      investigated and diagnosed as AOSD. He responded to steroids and was discharged
      on day 20.

PMID- 30186017
TI  - Uncommon Cause of Acute Liver Failure with Encephalopathy.

PMID- 30186018
TI  - Pseudo Bulbar Palsy: A Rare Cause of Extubation Failure.

PMID- 30186019
TI  - Unusual Cause of Hypotension in a Polytrauma Victim: A Case of Fahr's Syndrome.

PMID- 30186020
TI  - Selected Medication Safety Risks That Can Easily Fall Off the Radar Screen.
AB  - Part 1 of a 3-part series discusses 3 medication safety risks that can easily
      fall off the radar screen in hospitals and doctors' offices.

PMID- 30186022
TI  - Drug and Device News.
AB  - Approvals, new indications, regulatory activities, and more.

PMID- 30186021
TI  - Wide-Ranging Trump Drug Price Reduction Blueprint: Controversial Issues Included,
      Some Excluded.
AB  - President Trump's American Patients First plan to reduce drug prices has some
      innovative aspects but might face political roadblocks.

PMID- 30186023
TI  - Pharmaceutical Approval Update.
AB  - Baricitinib (Olumiant) tablets for rheumatoid arthritis; plazomicin (Zemdri)
      injection for complicated urinary tract infections; and cannabidiol (Epidiolex)
      oral solution for seizures with Lennox-Gastaut syndrome and Dravet syndrome.

PMID- 30186024
TI  - Dupilumab (Dupixent): An Interleukin-4 Receptor Antagonist for Atopic Dermatitis.
AB  - Dupilumab (Dupixent) for atopic dermatitis.

PMID- 30186025
TI  - Congress Readying User Fee Program for OTC Products: Money Needed to Dig FDA Out
      of Its Review Ditch.
AB  - Questions about the safety and efficacy of cough and cold medicines and numerous
      other over-the-counter (OTC) products-along with an overwhelmed, understaffed FDA
      are the driving force behind Congressional action to put a first-ever OTC user
      fee program in place.

PMID- 30186026
TI  - Challenges to the U.S. Health Care System From Legal and Regulatory Changes in
      the Donald Trump Era.
AB  - Despite a slow legislative start by President Trump, new federal and state
      regulatory health care changes will have important implications for pharmacists,
      P&T committees, and patients.

PMID- 30186027
TI  - Poly (ADP-ribose) Polymerase Inhibitors in the Management of Ovarian Cancer: A
      Drug Class Review.
AB  - Objective: To review the pharmacology, safety, efficacy, and role of poly
      adenosine diphosphate [ADP]-ribose polymerase (PARP) inhibitors in the treatment
      and maintenance of relapsed, advanced ovarian cancer. Summary: A total of 3 phase
      2 trials and 2 phase 3 trials were reviewed that evaluated the safety and
      efficacy of oral niraparib, olaparib, and rucaparib in patients with ovarian
      cancer. Progression-free survival (PFS) was evaluated in the maintenance setting
      for niraparib and olaparib, resulting in a PFS of 21.0 months and 8.4 months,
      respectively. Olaparib and rucaparib were evaluated in the treatment setting,
      producing a PFS of 9.4 months and 12.8 months, respectively. PFS was higher in
      patients with BRCA mutation when compared to patients with BRCA wild-type in both
      the maintenance and treatment setting across all trials evaluated. Niraparib,
      olaparib, and rucaparib were found to be relatively well tolerated in clinical
      trials, with the most common adverse events being anemia, fatigue, and nausea.
      Conclusion: PARP inhibitors appear to be a safe and effective new option in the
      treatment and maintenance of relapsed, advanced BRCA1/2 mutant ovarian cancer.
      This drug class will likely have an expanding role in ovarian cancer as further
      trial results are published.

PMID- 30186029
TI  - Research Briefs.

PMID- 30186028
TI  - 23rd Congress of the European Hematology Association.
AB  - We review key sessions on multiple myeloma, chronic lymphocytic leukemia, Hodgkin
      lymphoma, Epstein-Barr virus-positive post-transplant lymphoma, and follicular
      lymphoma.

PMID- 30186030
TI  - Fate, Transformation, and Toxicological Impacts of Pharmaceutical and Personal
      Care Products in Surface Waters.
AB  - With the growth of the human population, a greater quantity of pharmaceutical and
      personal care products (PPCPs) have been released into the environment. Although
      research has addressed the levels and the impact of PPCPs in the environment, the
      fate of these compounds in surface waters is neither well known nor
      characterized. In the environment, PPCPs can undergo various transformations that
      are critically dependent on environmental factors such as solar radiation and the
      presence of soil particles. Given that the degradation products of PPCPs are
      poorly characterized, these "secondary residues" can be a significant
      environmental health hazard due to their drastically different toxicologic
      effects when compared with the parent compounds. To better understand the fate of
      PPCPs, we studied the degradation of selected PPCPs, including ibuprofen and
      clofibric acid, in aqueous solutions that contained kaolinite clay and were
      irradiated with a solar simulator. The most abundant degradation products were
      identified and assessed for their toxicologic impact on selected microorganisms.
      The degraded mixtures showed lower toxicity than the starting compounds; however,
      as these degradation products are capable of further transformation and
      interaction with other PPCPs in natural waters, our work highlights the
      importance of additionally characterizing the PPCP degradation products.

PMID- 30186031
TI  - Leaf Damage by Phytophagous Beetles alters Terminalia catappa Green and Senesced
      Leaf Chemistry.
AB  - Chemical traits of Terminalia catappa L. leaves were determined on the island of
      Guam to understand the changes caused by beetle leaf herbivory. Green leaf
      chemistry indicated nitrogen was the most limiting nutrient in the climate and
      soils of Guam. The changes in leaf chemistry following beetle damage were
      extensive. Senesced leaf chemistry indicated beetle damage decreased some traits
      that predict lower leaf litter quality, such as lignin, but also decreased some
      traits that predict higher leaf litter quality, such as nitrogen. The
      stoichiometric traits based on carbon:macronutrient and lignin:macronutrient
      generally predicted higher quality leaf litter following beetle herbivory. The
      beetles that produce this form of T. catappa leaf damage on Guam are non-native,
      and overall, the results indicate these pests will increase the rate of litter
      decomposition and nutrient turnover in habitats where T. catappa is prevalent.

PMID- 30186032
TI  - Efficacy of Afternoon Plerixafor Administration for Stem Cell Mobilization.
AB  - Background: When used for hematopoietic stem cell mobilization, plerixafor was
      originally recommended to be administered 11 hours prior to apheresis based on
      the peak effect of 10 to 14 hours translating into an administration time of 10
      to 11 pm. Reports of post-plerixafor anaphylactic reactions mandated labeling
      change by the Food and Drug Administration with recommendation of monitoring
      patients after administration. Based on data suggesting sustained plerixafor
      activity at 18 hours, we changed our administration time to 4 pm at our center.
      Objective: The objective of this study is to compare the stem cell collection
      efficiency before and after the practice change at our institution. Methods: A
      retrospective chart review for patients with multiple myeloma, Hodgkin lymphoma,
      and non-Hodgkin lymphoma who received a plerixafor-containing mobilization
      regimen was conducted. The primary end point was the percentage of patients
      achieving the minimal CD34+ cell goal in ?2 apheresis days. The secondary end
      points included the percentage of patients achieving the preferred CD34+ cell
      goal in ?2 apheresis days, days of apheresis, total CD34+ cells Collected, and
      engraftment time. Results: A total of 208 patients (4 pm group n = 68, 10 pm
      group n = 140) with multiple myeloma (n = 112), Hodgkin lymphoma (n = 10), and
      non-Hodgkin lymphoma (n = 86) were included in the analysis. About 91% and 89% (P
      = .804) of the patients in the 4 and 10 pm groups, respectively, collected
      minimum cell dose. Preferred CD34+ cell goal was achieved in 57% and 53% of
      patients in the 4 and 10 pm groups, respectively. Conclusions: Late afternoon
      administration of plerixafor provides efficient stem cell mobilization.

PMID- 30186033
TI  - The Effect of Exercise on Oxygen Content in Anemic Patients With Chronic
      Obstructive Pulmonary Disease.
AB  - Background: Anemia is reported in one-third of the patients with chronic
      obstructive pulmonary disease (COPD). Anemia, by decreasing oxygen content, can
      be a contributing factor for hypoxemia. We determined to find whether anemia
      causes more prominent hypoxia by decreasing the total oxygen content after
      exercise in anemic patients with COPD. Methods: Stable moderate-to-severe COPD
      patients with and without anemia were recruited. Arterial blood gas analyses were
      performed on room air before and after a 6-minute walking test (6MWT). Walking
      distance, oxygen saturation, and heart rate were recorded in each case before and
      after the 6MWT. Pulmonary function test measurements and other data were obtained
      from the chart. The mean and standard deviations were calculated for continuous
      variables. The independent t-test and Kruskal-Wallis test were performed for
      numerical covariate and univariate analyses. The paired t-test was used for the
      analyses of data before and after exercise. Results: A total of 24 male patients
      were included in the study; 12 of which were anemic. The oxygen content was
      decreased in the anemic group (15.22 +/- 1.28 vs 15.07 +/- 1.22) after exercise,
      but it was not significant. In the non-anemic group, no oxygen content decrease
      was observed after exercise (18.83 +/- 1.41 vs 18.9 +/- 1.37). Interestingly, the
      Spo2, but not Sao2, was significantly lower after exercise in anemic patients
      with COPD (93.46% +/- 5.06% vs 88.20% +/- 6.35% before and after exercise,
      respectively). Conclusions: Anemia does not cause more prominent hypoxemia after
      exercise in patients with COPD. However, the recorded Spo2 levels were
      significantly lower after exercise in the anemic patients with COPD.

PMID- 30186034
TI  - Investigating the importance of edge-structure in the loss of H/H2 of PAH
      cations: the case of dibenzopyrene isomers.
AB  - We present a detailed study of the main dehydrogenation processes of two
      dibenzopyrene cation (C24H14+) isomers, namely dibenzo(a,e)pyrene (AE+) and
      dibenzo(a,l)pyrene (AL+). First, action spectroscopy under VUV photons was
      performed using synchrotron radiation in the 8-20 eV range. We observed lower
      dissociation thresholds for the non-planar molecule (AL+) than for the planar one
      (AE+) for the main dissociation pathways: H and 2H/H2 loss. In order to
      rationalize the experimental results, dissociation paths were investigated by
      means of density functional theory calculations. In the case of H loss, which is
      the dominant channel at the lowest energies, the observed difference between the
      two isomers can be explained by the presence in AL+ of two C-H bonds with
      considerably lower adiabatic dissociation energies. In both isomers the 2H/H2
      loss channels are observed only at about 1 eV higher than H loss. We suggest that
      this is due to the propensity of bay H atoms to easily form H2. In addition, in
      the case of AL+, we cannot exclude a competition between 2H and H2 channels. In
      particular, the formation of a stable dissociation product with a five-membered
      ring could account for the low energy sequential loss of 2 hydrogens. This work
      shows the potential role of non-compact PAHs containing bay regions in the
      production of H2 in space.

PMID- 30186036
TI  - Patients' perspectives regarding hospital visits in the universal health coverage
      system of Thailand: a qualitative study.
AB  - Background: A universal health coverage policy was implemented in Thailand in
      2002 and led to an increase in accessibility to, and equity of, healthcare
      services. The Thai government and academics have focused on the large-scale
      aspects, including effectiveness and impacts, of universal health coverage over
      one decade. Here, we aimed to identify patients' perspectives on hospital visits
      under universal health coverage. Methods: A qualitative study was carried out in
      four public hospitals in rural Thailand. We collected data through focus group
      discussions (FGDs) and in-depth interviews (IDIs). The semi-structured interview
      guide was designed to elicit perspectives on hospital visits among participants
      covered by the Universal Coverage Scheme, Social Security Scheme or Civil Servant
      Medical Benefit Scheme. Data were transcribed and analysed using a thematic
      approach. Results: Twenty-nine participants (mean age, 56.76 +/- 16.65 years)
      participated in five FGDs and one IDI. The emerging themes and sub-themes were
      identified. Factors influencing decisions to visit hospitals were free healthcare
      services, perception of serious illness, the need for special tests, and
      continuity of care. Long waiting times were barriers to hospital visits.
      Employees, who could not leave their work during office hours, could not access
      some services such as health check-ups. From the viewpoint of participants,
      public hospitals provided quality and equitable healthcare services.
      Nevertheless, shared decision making for treatment plans was not common.
      Conclusions: The factors and barriers to utilisation of healthcare services
      provide exploratory data to understand the healthcare-seeking behaviours of
      patients. Perceptions towards free services under universal health coverage are
      positive, but participation in decision making is rare. Future studies should
      focus on finding ways to balance the needs and barriers to hospital visits and to
      introduce the concept of shared decision making to both doctors and patients.

PMID- 30186037
TI  - Inflammation and LPS-Binding Protein Enable the Stimulatory Effect of Endotoxin
      on Prolactin Secretion in the Ovine Anterior Pituitary: Ex Vivo Study.
AB  - Prolactin is a hormone that plays an important role in the regulation of many
      physiological processes including lactation, reproduction, fat metabolism, and
      immune response. The secretion of prolactin could be disturbed by an immune
      stress commonly accompanying infection. This study was designed to determine the
      influence of bacterial endotoxin-lipopolysaccharide (LPS)-on prolactin gene (PRL)
      expression and prolactin release from the ovine anterior pituitary (AP) explants
      collected from saline- and LPS-treated ewes in the follicular phase. The
      expressions of toll-like receptor 4 (TLR4) and proinflammatory cytokines
      interleukin- (IL-) 1beta, IL-6, and tumor necrosis factor- (TNF-) alpha genes
      were also assayed. The results of the study showed that LPS stimulates prolactin
      secretion and IL-6 gene expression in the AP explants, but its action on
      lactotrophs depends on the immunological status of animal. It was demonstrated
      that an important role in enhancing the effect of LPS on the pituitary in the
      saline-treated ewes is played by LPS-binding protein (LBP)- "adapter molecule"
      for LPS binding to the cell surface receptor CD14 and then to TLR4. Also, it was
      found that bacterial endotoxin acting on the anterior pituitary cells may enhance
      prolactin secretion, and this effect of LPS could be mediated by IL-6 which is
      known as prolactin-releasing factor. Identification of the neuroendocrine and
      immune interactions in the regulation of prolactin secretion could be helpful in
      developing newer and more effective treatments for dysfunctions connected with
      disorders in this hormone secretion.

PMID- 30186035
TI  - Cu(II) binding to various forms of amyloid-beta peptides. Are they friends or
      foes?
AB  - In the present micro-review, we describe the Cu(II) binding to several forms of
      amyloid-beta peptides, the peptides involved in Alzheimer's disease. It has
      indeed been shown that in addition to the "full-length" peptide originating from
      the precursor protein after cleavage at position 1, several other shorter
      peptides do exist in large proportion and may be involved in the disease as well.
      Cu(II) binding to amyloid-beta peptides is one of the key interactions that
      impact both the aggregating properties of the amyloid peptides and the Reactive
      Oxygen Species (ROS) production, two events linked to the etiology of the
      disease. Binding sites and affinity are described in correlation with Cu(II)
      induced ROS formation and Cu(II) altered aggregation, for amyloid peptides
      starting at position 1, 3, 4, 11 and for the corresponding pyroglutamate forms
      when they could be obtained (i.e. for peptides cleaved at positions 3 and 11). It
      appears that the current paradigm which points out a toxic role of the Cu(II) -
      amyloid-beta interaction might well be shifted towards a possible protective role
      when the peptides considered are the N-terminally truncated ones.

PMID- 30186039
TI  - Voluntary stopping of eating and drinking (VSED) as an unknown challenge in a
      long-term care institution: an embedded single case study.
AB  - Background: Chronically ill persons experience conditions of life that can become
      unbearable, resulting in the wish to end their life prematurely. Relatives
      confronted with this wish experience ambivalence between loyalty to the person's
      desire to die and the fear of losing this person. Caring for a person during the
      premature dying process can be morally challenging for nurses. One way to end
      one's life prematurely is Voluntary Stopping of Eating and Drinking (VSED).
      Methods: This embedded single case study explored the experiences of registered
      nurses (embedded units of analysis: ward manager, nursing manager, nursing
      expert) and relatives who accompanied a 49-year-old woman suffering from multiple
      sclerosis during VSED in a Swiss long-term care institution (main unit of
      analysis). By means of a within-analysis, we performed an in-depth analysis of
      every embedded unit of analysis and elaborated a central phenomenon for each
      unit. Afterwards, we searched for common patterns in a cross-analysis of the
      embedded units of analysis in order to develop a central model. Results: The
      following central concept emerged from cross-analysis of the embedded units of
      analysis: As a way of ending one's life prematurely, VSED represents an
      unfamiliar challenge to nurses and relatives in the field of tension between
      one's personal attitude and the agents' concerns, fears and uncertainties.
      Particularly significant is the personal attitude, influenced on the one hand by
      one's own experiences, prior knowledge, role and faith, on the other hand by the
      VSED-performing person's age, disease and deliberate communication of the
      decision. Depending on the intention of VSED as either suicide or natural dying,
      an accepting or dismissing attitude evolves on an institutional and personal
      level. Conclusions: To deal professionally with VSED in an institution, it is
      necessary to develop an attitude on the institutional and personal level.
      Educational measures and quality controls are required to ensure that VSED
      systematically becomes an option to hasten death. As VSED is a complex
      phenomenon, it is necessary to include palliative care in practice development
      early on and comprehensively. There is a high need of further research on this
      topic. Particularly, qualitative studies and hypothesis-testing approaches are
      required.

PMID- 30186038
TI  - Interleukin 6 and 10 Serum Levels and Genetic Polymorphisms in Children with Down
      Syndrome.
AB  - Immunological impairment is a condition that is often observed in individuals
      with Down syndrome (DS). The immune response is modulated by pro- and anti
      inflammatory cytokines whose expressions could be influenced by genetic
      polymorphisms. The present study was aimed at evaluating the frequencies of 
      174G>C, -572G>C, and -597G>A polymorphisms in the interleukin 6 (IL-6) gene and 
      592C>A, -1082A>G, and -819C>T polymorphisms in the IL-10 gene and the IL-6 and IL
      10 serum levels in healthy individuals with and without DS. The authors also
      aimed to investigate the impact of the genotypes on the interleukin
      concentrations. The genetic polymorphisms were investigated in 200 DS individuals
      and 200 controls without DS. The serum measurement of IL-6 and IL-10 was
      performed in a subgroup (54 cases and 54 controls) by enzyme-linked immunosorbent
      assay (ELISA). The frequencies of the polymorphisms and haplotypes evaluated were
      not different between individuals with and without DS. IL-10 concentration was
      higher in DS children but was not influenced by IL-10 gene polymorphisms. IL-6
      genotypes had no influence on IL-6 serum levels. The IL-10 serum levels are
      increased in DS individuals, but IL-10 polymorphisms are not the main factors
      that influence the IL-10 expression in DS.

PMID- 30186040
TI  - MiR-384 inhibits the proliferation of colorectal cancer by targeting AKT3.
AB  - Background: Growing evidence suggests that MiRNAs play essential roles in the
      initiation and progression of colorectal cancer (CRC). The aberrant expression of
      miR-384 has been reported in some cancers. However, the role and mechanism of miR
      384 in CRC proliferation remains unknown. Methods: The expression of miR-384 was
      detected in CRC and their paired normal tissues by real-time PCR. In vivo and in
      vitro assays were conducted to confirm the role of miR-384 in the proliferation
      of CRC. Bioinformatics analysis, luciferase reporter assays, western blot and in
      vitro assays were used to confirm that AKT3 was the target gene of miR-384.
      Finally, Spearman's correlation analyses was carried out to analyze the
      relationship between miR-384 expression and AKT3 expression in CRC. Results: MiR
      384 was down-regulated in CRC tissues. The in vivo and vitro functional assays
      verified that the ectopic upregulation of miR-384 inhibited the proliferation of
      CRC and the inhibition of miR-384 promoted the proliferation of CRC.
      Bioinformatics analysis, luciferase reporter assays, western blot and in vitro
      functional assays confirmed AKT3 as the target gene of miR-384. The expression of
      miR-384 was negatively correlated with the expressions of AKT3. Conclusion: Our
      study verified that miR-384 could significantly suppress the proliferation of CRC
      by directing targeting AKT3.

PMID- 30186041
TI  - ZFAS1: a novel tumor-related long non-coding RNA.
AB  - Long non-coding RNAs (lncRNA) are classified as a kind of RNA, which are longer
      than 200 nucleotides in length and cannot be translated into proteins. Multiple
      studies have demonstrated that lncRNAs are involved in various cellular
      processes, including proliferation, differentiation, cell death, and metastasis.
      In addition, aberrant expression of lncRNAs has been discovered in human tumors,
      where they function as either oncogenes or tumor suppressor genes. Among numerous
      lncRNAs, we focus on ZNFX1 antisense RNA 1 (ZFAS1), a well-known lncRNA that is
      aberrant overexpression in various tumors, including melanoma, esophageal
      squamous cell carcinoma, non-small cell lung cancer, gastric cancer, colon
      cancer, and Hepatocellular carcinoma, in which it functions as oncogene. In
      contrast, ZFAS1 is downregulated in breast cancer, which may function as tumor
      suppressor gene. In this review, we provide an overview of current evidence
      concerning the role and potential clinical utilities of ZFAS1 in human cancers.

PMID- 30186042
TI  - Expression of B7-H6 expression in human hepatocellular carcinoma and its clinical
      significance.
AB  - Background: Recent studies have suggested that B7-H6, a new member of the B7
      family of ligands, not only is a crucial regulator of NK cell-mediated immune
      responses but also has important clinical implications due to its abnormal
      expression in many human cancers. We have previously reported that higher B7-H6
      expression levels in ovarian cancer tissues are positively correlated with tumor
      metastasis and cancer progression. To date, the expression of B7-H6 in human
      hepatocellular carcinoma (HCC) and the clinical significance of B7-H6 expression
      still remain elusive. Methods: In the present study, the expression level of B7
      H6 was examined in both HCC tissues and HCC cell lines (HepG2 and SMMC-7721). And
      the clinical significance of B7-H6 was analyzed as well. Results: Our results
      revealed that B7-H6 was expressed abnormally in HCC tissues, which was greatly
      related to tumor size. The TCGA data also showed that the B7-H6 mRNA expression
      level was significantly negatively correlated with the survival of HCC patients.
      Next, to investigate the functions of B7-H6 in HCC, we successfully constructed
      B7-H6 knockdown expression human HCC cell lines using the RNA interference
      technology. Our studies showed that reduced expression of B7-H6 in HepG2 and SMMC
      7721 cells significantly attenuated cell proliferation as well as cell migration
      and invasion. Besides, depletion of B7-H6 greatly induced cell cycle arrest at G1
      phase. And also B7-H6 knockdown in HCC cell lines dramatically decreased the C
      myc, C-fos and Cyclin-D1 expression. Conclusions: Our present findings suggested
      that B7-H6 played an important role in oncogenesis of HCC on cellular level, and
      B7-H6 could be employed to develop immunotherapeutic approaches targeting this
      malignancy.

PMID- 30186044
TI  - Charisma and the clinic.
AB  - Here we argue that 'charisma', a concept widely taken up within geography and the
      environmental humanities, is of utility to the social studies of medicine.
      Charisma, we suggest, draws attention to the affective dimensions of medical
      work, the ways in which these affective relations are structured, and the manner
      in which they are intimately tied to particular material-discursive contexts. The
      paper differentiates this notion of charisma from Weber's analyses of the
      'charismatic leader' before detailing three forms of charisma - ecological (which
      relates to the affordances an entity has), corporeal (related to bodily
      interaction) and aesthetic (pertaining to an entity's initial visual and
      emotional impact). Drawing on interview data, we then show how this framework can
      be used to understand the manner in which psychologists and neuroscientists have
      come to see and act on autism. We conclude the article by suggesting that
      examining charisma within healthcare settings furthers the concept, in particular
      by drawing attention to the discursive features of ecologies and the 'non
      innocence' of charisma.

PMID- 30186043
TI  - The involvement of osmolarity in the safety of contrast media.
AB  - Background: New non-ionic contrast agents, classified into low osmolar agents and
      iso-osmolar agents, present different biochemical characteristics that may
      influence the allergic reactions they cause. The aim of our study was to evaluate
      how osmolarity may affect safety in the use of contrast agents. Case
      presentation: Six patients with a positive history for reaction to contrast agent
      were included in this study. Only one patient prick and intradermal skin test was
      positive. However, in 5 cases, patients presented an immediate reaction after
      administration of contrast agent that was not IgE mediated. Conclusions: In this
      study, we focused on iodixanol, an iso-osmolar contrast agent, finding good
      safety of this product in patients with previous hypersensitivity reactions to
      contrast agent.

PMID- 30186047
TI  - "Miscellaneous" Tumors of the Small Bowel and Colon and Rectum.

PMID- 30186046
TI  - Vassiliki "Liana" Tsikitis, MD, MCR, FACS, FASCRS.

PMID- 30186045
TI  - COSIMO - patients with active cancer changing to rivaroxaban for the treatment
      and prevention of recurrent venous thromboembolism: a non-interventional study.
AB  - Background: Around 20% of venous thromboembolism (VTE) cases occur in patients
      with cancer. Current guidelines recommend low molecular weight heparin (LMWH) as
      the preferred anticoagulant for VTE treatment. However, some guidelines state
      that vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs) are
      acceptable alternatives for long-term therapy in some patients if LMWHs are not
      available. LMWHs and VKAs have a number of drawbacks that can increase the burden
      on patients. DOACs, such as rivaroxaban, can ameliorate some burdens and may
      offer an opportunity to increase patient satisfaction and health-related quality
      of life (HRQoL). The Cancer-associated thrOmboSIs - patient-reported outcoMes
      with rivarOxaban (COSIMO) study is designed to provide real-world information on
      treatment satisfaction in patients with active cancer who switch from LMWH or VKA
      to rivaroxaban for the treatment of acute VTE or to prevent recurrent VTE.
      Methods: COSIMO is a prospective, non-interventional, single-arm cohort study
      that aims to recruit 500 patients in Europe, Canada and Australia. Adults with
      active cancer who are switching to rivaroxaban having received LMWH/VKA for the
      treatment and secondary prevention of recurrent VTE for at least the previous 4
      weeks are eligible. Patients will be followed for 6 months. The primary outcome
      is treatment satisfaction assessed as change in the Anti-Clot Treatment Scale
      (ACTS) Burdens score at week 4 after enrolment compared with baseline. Secondary
      outcomes include treatment preferences, measured using a discrete choice
      experiment, change in ACTS Burdens score at months 3 and 6, and change in HRQoL
      (assessed using the Functional Assessment of Chronic Illness Therapy - Fatigue
      questionnaire). COSIMO will collect data on patients' medical history, patterns
      of anticoagulant use and incidence of bleeding and thromboembolic events. Study
      recruitment started in autumn 2016. Conclusions: COSIMO will provide information
      on outcomes associated with switching from LMWH or VKA therapy to rivaroxaban for
      the treatment or secondary prevention of cancer-associated thrombosis in a real
      life setting. The key goal is to assess whether there is a change in patient
      reported treatment satisfaction. In addition, COSIMO will facilitate the
      evaluation of the safety and effectiveness of rivaroxaban in preventing recurrent
      VTE in this patient population. Trial registration: NCT02742623. Registered 19
      April 2016.

PMID- 30186048
TI  - Small Bowel Adenocarcinoma.
AB  - Small bowel adenocarcinoma is a clinically and anatomically distinct
      gastrointestinal cancer that lacks prospective data to support its optimal
      management. Patients with inflammatory bowel disease and inherited conditions
      that cause gastrointestinal polyps are at especially high risk. Due to a lack of
      effective surveillance programs resulting in missed or delayed diagnoses only
      when symptoms develop, this disease is generally discovered at an advanced stage.
      Surgical resection is the only treatment modality with a chance of cure.
      Currently accepted treatment considerations are often generalized from large
      bowel and pancreatic-biliary cancers, due to some anatomic and clinical
      parallels. Additional research, however, is desperately needed to characterize
      the unique molecular differences of this disease to better prognosticate patients
      and establish rational clinical trials that would improve their outcomes.

PMID- 30186049
TI  - Appendiceal Neoplasms.
AB  - Appendiceal neoplasms are identified in 0.9 to 1.4% of appendiceal specimens, and
      the incidence is increasing. It has long been professed that neuroendocrine
      tumors (formerly carcinoids) are the most common neoplastic process of the
      appendix; recent data, however, has suggested a shift in epidemiology. Our intent
      is to distill the complex into an algorithm, and, in doing so, enable the surgeon
      to seamlessly maneuver through operative decisions, treatment strategies, and
      patient counseling. The algorithm for evaluation and treatment is complex, often
      starts from the nonspecific presenting complaint of appendicitis, and relies
      heavily on often subtle histopathologic differences.

PMID- 30186050
TI  - The Role of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy
      for Appendiceal Tumors and Colorectal Adenocarcinomas.
AB  - Peritoneal surface disease (PSD) has historically been used interchangeably with
      the term peritoneal carcinomatosis (PC) and has a dismal natural history. A
      variety of malignant pathologies, including colorectal and appendiceal primary
      tumors, can disseminate throughout the peritoneal cavity, leading to bowel
      obstruction and death. In general, peritoneal spread from high-grade appendiceal
      and colorectal primaries has the potential of hepatic and distant spread and best
      classified as PC. Low-grade appendiceal tumors are better categorized as PSD, due
      to low cellularity, high mucin production, and lack of potential spread outside
      the peritoneal cavity. Growing international experience with cytoreductive
      surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) over the past 30
      years has presented a therapeutic option to patients with PSD from colorectal and
      appendiceal tumors that can provide significant disease control, as well as
      potential for previously unattainable long-term survival. The proliferation of
      HIPEC centers and ongoing prospective trials are helping to standardize HIPEC
      techniques and patient selection.

PMID- 30186051
TI  - Gastrointestinal Stromal Tumors of the Distal Gastrointestinal Tract.
AB  - Gastrointestinal stromal tumors (GISTs) are rare in occurrence, but comprise the
      most common mesenchymal tumors of the gastrointestinal tract and affect between
      15 and 20 individuals per million per year. Due to recent advancements in
      molecular classification of these tumors, medical therapy has provided improved
      outcomes to a historically surgically managed disease. This review article
      briefly discusses the molecular characteristics, medical and surgical therapies,
      and future of GIST management.

PMID- 30186052
TI  - Small Bowel and Colorectal Carcinoids.
AB  - Neuroendocrine tumors, or carcinoid tumors, of both the midgut and hindgut are
      quite rare, but their incidence is increasing. Surgery is the treatment of choice
      in patients who can tolerate an operation and have operable disease. Options for
      the treatment of metastatic disease include cytoreductive surgery, somatostatin
      analogues, interferon alpha, local liver therapies (hepatic arterial
      embolization, ablation), chemotherapy, Peptide-Receptor Radionucleotide
      Radiotherapy, angiogenesis inhibitors, and mammalian target of rapamycin
      inhibitors.

PMID- 30186053
TI  - Colorectal Lymphoma: A Review.
AB  - Non-Hodgkin lymphoma (NHL) that primarily involves the colon is rare and should
      be distinguished from the more common systemic nodal lymphoma. It has unique
      clinical expectations and management consideration. Different histologic subtypes
      of NHL involve the colon, which varies in the clinical behavior and likelihood of
      obtaining durable remissions with treatment. This article will review the current
      understanding of the different histologic subtypes of primary colorectal lymphoma
      and propose management algorithms.

PMID- 30186055
TI  - Awareness and Knowledge of Occupational Therapy among Nigerian Medical and Health
      Sciences Undergraduates.
AB  - Objective/Background: Consequent to the introduction of occupational therapy (OT)
      training programmes in Nigeria in the past decade, this study sought to assess
      the awareness and knowledge of Nigerian medical and other health career
      undergraduates about OT. Methods: Three hundred and eighty-one undergraduates and
      students of other health disciplines from the College of Health Sciences, Obafemi
      Awolowo University (OAU), Ile-Ife, Nigeria responded to a validated three section
      questionnaire assessing their awareness and knowledge about OT. The collected
      data were analysed using descriptive statistics of mean and percentages and
      inferential statistics of chi-square test of association. Results: The mean age
      of the respondents was 20.96 +/-2.88 years. Over 80% of the respondents were
      aware of the OT profession, with higher rates among male respondents (83.7%),
      students in the 2nd year of study (94.7%), and those in the medical
      rehabilitation programme (99.1%). Amongst the respondents, < 40% had good
      knowledge of OT while a majority had knowledge ranging from poor to moderate
      (62.7%). Respondents' course of study and level of study were significantly
      associated with awareness and knowledge about OT. Conclusion: Nigerian medical
      and health sciences undergraduates had high awareness, but poor to moderate
      knowledge about the OT profession, roles, and work settings. Level of awareness
      and knowledge about OT were significantly influenced by the rehabilitation
      related course of study and lower level of study. Replication of similar studies
      in countries with different cultural backgrounds is suggested.

PMID- 30186054
TI  - Antibiotic treatment modulates protein components of cytotoxic outer membrane
      vesicles of multidrug-resistant clinical strain, Acinetobacter baumannii DU202.
AB  - Background: Outer membrane vesicles (OMVs) of Acinetobacter baumannii are
      cytotoxic and elicit a potent innate immune response. OMVs were first identified
      in A. baumannii DU202, an extensively drug-resistant clinical strain. Herein, we
      investigated protein components of A. baumannii DU202 OMVs following antibiotic
      treatment by proteogenomic analysis. Methods: Purified OMVs from A. baumannii
      DU202 grown in different antibiotic culture conditions were screened for
      pathogenic and immunogenic effects, and subjected to quantitative proteomic
      analysis by one-dimensional electrophoresis and liquid chromatography combined
      with tandem mass spectrometry (1DE-LC-MS/MS). Protein components modulated by
      imipenem were identified and discussed. Results: OMV secretion was increased >
      twofold following imipenem treatment, and cytotoxicity toward A549 human lung
      carcinoma cells was elevated. A total of 277 proteins were identified as
      components of OMVs by imipenem treatment, among which beta-lactamase OXA-23,
      various proteases, outer membrane proteins, beta-barrel assembly machine
      proteins, peptidyl-prolyl cis-trans isomerases and inherent prophage head subunit
      proteins were significantly upregulated. Conclusion: In vitro stress such as
      antibiotic treatment can modulate proteome components in A. baumannii OMVs and
      thereby influence pathogenicity.

PMID- 30186056
TI  - Rehabilitation Interventions for Poststroke Hand Oedema: A Systematic Review.
AB  - Objective/Background: To review the evidence of rehabilitation interventions for
      the management of poststroke hand oedema. Methods: We conducted a systematic
      review of research articles in electronic databases published in English between
      1999 and 2015. Two investigators working independently retrieved articles from
      the Cochrane Central Register of Controlled Trials, SCOPUS, Taylor & Francis
      Online, Wiley Online Library, CINAHL, Springer (MetaPress), ScienceDirect,
      PubMed, SAGE Journals Online, EBSCO, and Web of Science. Only controlled trials
      with outcome measures and interventions for poststroke hand oedema were included.
      Three investigators critically appraised the selected studies using the
      Physiotherapy Evidence Database Scale. Results: Of the 189 articles identified,
      nine (5 randomized controlled trials, 3 nonrandomized controlled trials, and 1
      crossover controlled trial) were selected. These studies are heterogeneous in
      terms of design and types of intervention for poststroke hand oedema. The
      interventions reducing hand oedema are Lycra pressure garments with glove
      splints, bilateral passive motion upper-limb exercises, laser therapy, and
      acupressure. However, due to these studies' short intervention periods and the
      fact that hand oedema is not their primary outcome measure, it is not possible to
      draw a firm conclusion on their clinical significance for managing poststroke
      hand oedema. Conclusion: Further study needs to focus solely on interventions for
      poststroke hand oedema and their long-term effects. No conclusion can be made on
      the most effective management of poststroke hand oedema until much more evidence
      is available.

PMID- 30186057
TI  - Enhancing Occupational Therapy Students' Knowledge, Competence, Awareness, and
      Interest in Accessibility.
AB  - Objective/Background: The purpose of this study was to assess whether the
      incorporation of an environmental assessment for accessibility, as part of an
      "Activity Analysis" course, would enhance new students' knowledge, competence,
      awareness, and interest in accessibility issues for people with disabilities.
      Methods: In this research, we included an out-of-class training of environmental
      assessment for accessibility. One hundred and two 1st-year occupational therapy
      students at Tel Aviv University participated in this research. Of the 102
      participants, 56 experienced the training and 46 did not but attended the regular
      Activity Analysis course. The students explored a typical community environment,
      during which a specific checklist was used for assessing levels of accessibility.
      The "Accessibility-Knowledge Competence Awareness and Interests" questionnaire
      was administered before and after the course to both groups. Results: Students
      who participated in the out-of-class training showed significant increases in
      their knowledge, competence, and partial awareness of accessibility and also had
      better grades in two separate courses that required knowledge of accessibility.
      There was no significant difference in the results of the Accessibility-Knowledge
      Competence Awareness and Interests before and after the Activity Analysis course
      in the control group. Conclusion: The findings of the current study support the
      contribution of teaching 1st-year occupational therapy students the principles
      and practices of accessibility for people with disabilities, by improving their
      knowledge and level of competence at this early stage of their professional
      lives. Further studies are needed, however, to determine the optimal course of
      implementation in order to enhance awareness and interest in the subject of
      accessibility.

PMID- 30186058
TI  - Adolescents with Cancer and Occupational Deprivation in Hospital Settings: A
      Qualitative Study.
AB  - Objective/Background: The aim of this article was to analyze the needs of
      hospitalized adolescents with cancer in relation to the performance of meaningful
      activities as well as to explore the possible scenarios of occupational
      deprivation in hospital paediatric wards. Methods: The study follows an
      ethnographical research approach using two techniques: participant observation
      and in-depth interviews, with constant comparison by data triangulation. Eight
      adolescents diagnosed with cancer aged between 15 years and 19 years (5 males and
      3 females) were recruited from Toledo and Madrid in Spain. Results: Five themes
      revealing the needs of adolescents with cancer in hospital environments were
      identified: (a) educational needs, (b) leisure needs, (c) physical space of the
      rooms, (d) interaction with medical personnel, and (e) lack of specific wards for
      adolescents. Conclusion: The lack of variety and availability of educational
      activities and leisure, and the subsequent changes of the individual physical,
      social, and cultural environments could cause situations of occupational
      deprivation, and also affect the health and quality of life of the individuals.

PMID- 30186059
TI  - Relationships between Depression and Stress Factors in Housework and Paid Work
      among Japanese Women.
AB  - Objective/Background: The prevalence of depression in women is two times as much
      as that in men. However, the rehabilitation programme for return to work for
      patients with depression in Japan mainly focuses on male individuals. Japanese
      working women usually have the central role in housework in addition to paid
      work. Therefore, we hypothesized that Japanese working women with depression need
      a support programme for housework as well as paid work. The purpose of this study
      was to investigate the stress factors relevant to the existence of depression, in
      both paid work and housework, among working women. Methods: This study recruited
      35 women with depression and 35 women without depression. We carried out a cross
      sectional investigation with two questionnaires having the same structure: The
      National Institute for Occupational Safety and Health (NIOSH) Generic Job Stress
      Questionnaire (for paid work) and the NIOSH Generic Housekeeping Labor Stress
      Questionnaire (for housework). We extracted the stress factors contributing to
      the existence of depression using logistic regression. Results: Three stress
      factors were found--two in housework, and one in paid work. In housework,
      variance in workload and underutilization of abilities were associated with the
      presence of depression. In paid work, interpersonal conflict was an associated
      factor. Conclusion: Rehabilitation programmes involving variance in workload and
      under self-evaluation in housework, and interpersonal conflict in paid work must
      be adequately addressed to support working women with depression.

PMID- 30186060
TI  - Purposeful Activity in Psychiatric Rehabilitation: Is Neurogenesis a Key Player?
AB  - Adult neurogenesis, defined as the generation of new neurons in adulthood, has
      been a fascinating discovery in neuroscience, as the continuously replenishing
      neuronal population provides a new perspective to understand neuroplasticity.
      Besides maintaining normal physiological function, neurogenesis also plays a key
      role in pathophysiology and symptomatology for psychiatric conditions. In the
      past decades, extensive effort has been spent on the understanding of the
      functional significance of neurogenesis in psychiatric conditions, mechanisms of
      pharmacological treatment, and discovery of novel drug candidates for different
      conditions. In a clinical situation, however, long-term rehabilitation treatment,
      in which occupational therapy is the key discipline, is a valuable, economical,
      and commonly used treatment alternative to psychotropic medications.
      Surprisingly, comparatively few studies have investigated the biological and
      neurogenic effects of different psychiatric rehabilitative treatments. To address
      the possible linkage between psychiatric rehabilitation and neurogenesis, this
      review discusses the role of neurogenesis in schizophrenia, major depression, and
      anxiety disorders. The review also discusses the potential neurogenic effect of
      currently used psychiatric rehabilitation treatments. With a better understanding
      of the biological effect of psychiatric rehabilitation methods and future
      translational studies, it is hoped that the therapeutic effect of psychiatric
      rehabilitation methods could be explained with a novel perspective. Furthermore,
      this knowledge will benefit future formulation of treatment methods, especially
      purposeful activities in occupational therapy, for the treatment of psychiatric
      disorders.

PMID- 30186061
TI  - Tactile Perception for Stroke Induce Changes in Electroencephalography.
AB  - Objective/Background: Tactile perception is a basic way to obtain and evaluate
      information about an object. The purpose of this study was to examine the effects
      of tactile perception on brain activation using two different tactile
      explorations, passive and active touches, in individuals with chronic hemiparetic
      stroke. Methods: Twenty patients who were diagnosed with stroke (8 right brain
      damaged, 12 left brain damaged) participated in this study. The tactile
      perception was conducted using passive and active explorations in a sitting
      position. To determine the neurological changes in the brain, this study measured
      the brain waves of the participants using electroencephalography (EEG). Results:
      The relative power of the sensory motor rhythm on the right prefrontal lobe and
      right parietal lobe was significantly greater during the active tactile
      exploration compared to the relative power during the passive exploration in the
      left damaged hemisphere. Most of the measured brain areas showed nonsignificantly
      higher relative power of the sensory motor rhythm during the active tactile
      exploration, regardless of which hemisphere was damaged. Conclusion: The results
      of this study provided a neurophysiological evidence on tactile perception in
      individuals with chronic stroke. Occupational therapists should consider an
      active tactile exploration as a useful modality on occupational performance in
      rehabilitation training.

PMID- 30186062
TI  - Factors Influencing Rehospitalisation of Patients with Schizophrenia in Japan: A
      1-year Longitudinal Study.
AB  - Objective/Background: This longitudinal study explored factors influencing the
      rehospitalisation of patients with schizophrenia in Japan. Methods: Participants
      comprised patients with schizophrenia who were discharged from a psychiatric
      hospital in Japan. The investigations were conducted at the time of discharge and
      one year later. Demographics and clinical characteristics included the following:
      the type of occupational therapy (OT) interventions (group and individualized or
      group only); the assessment scales' scores on hospitalisation; the community
      living conditions after discharge; and the contents of outpatient treatment
      (outpatient OT, day-care treatment, home-visit nursing, and adherence to
      outpatient treatment and medication). All variables were examined in a binomial
      logistic regression analysis to identify the factors for rehospitalisation.
      Results: The rehospitalisation rate was 31.8%, as 14 of 44 participants were
      rehospitalised within one year after discharge. The type of OT interventions (OR
      = 7.05, 95% CI = 1.36 -36.69, p = .020) and the adherence to outpatient treatment
      and medication (OR = 9.48, 95% CI = 1.82-49.33, p = .008) were significant
      contributing factors to rehospitalisation. Conclusion: This study provided
      preliminary support for the finding that individualized occupational therapy and
      proper adherence to outpatient treatment and medication are associated with
      reducing the rehospitalisation of patients with schizophrenia in Japan.

PMID- 30186063
TI  - Impact of Cognitive and Psychological Symptoms on Work Productivity and Quality
      of Life among Breast Cancer Survivors in Hong Kong.
AB  - Objective/Background: Employed breast cancer survivors (BCS) may experience
      residual symptoms that can impact their work productivity and quality of life
      (QoL), but it is unclear whether such associations exist among BCS in Hong Kong.
      Therefore, this study was designed to explore the symptom burden (cognitive
      limitation and psychological distress) of employed BCS in HK, and to investigate
      whether such factors are related to work productivity and QoL. Methods: A cross
      sectional study including employed BCS (n = 30), women with musculoskeletal
      conditions (n = 30), and healthy women (n = 30) was conducted. Participants
      completed a questionnaire covering their sociodemographics, the Hospital Anxiety
      and Depression Scale, Cognitive Symptom Checklist, Work Limitation Questionnaire,
      and European Organization for Research and Treatment of Cancer Quality of Life
      Questionnaire C30. Results: The self-perceived cognitive limitations at work of
      BCS were significantly higher than that of the healthy control group (5.33 vs.
      2.60; p < .05). The cognitive limitations in BCS were significantly associated
      with their QoL (beta = -0.320; p = .032). A negative relationship between
      depression and QoL in BCS was also observed in this study. Conclusion: This
      exploratory study provides local evidence that BCS experience greater work-task
      related cognitive limitations and that is related to QoL. Similar to findings in
      other countries, this provides insight for the consideration of early
      identification of cognitive problems in this particular patient group. Further
      studies may be needed to further substantiate such findings and to examine the
      effectiveness of potential cognitive interventions.

PMID- 30186064
TI  - Effectiveness of Earmuffs and Noise-cancelling Headphones for Coping with Hyper
      reactivity to Auditory Stimuli in Children with Autism Spectrum Disorder: A
      Preliminary Study.
AB  - Objective/Background: The purpose of this pilot study was to examine the
      effectiveness of standard earmuffs and noise-cancelling (NC) headphones in
      controlling behavioural problems related to hyper-reactivity to auditory stimuli
      in children with autism spectrum disorder (ASD). Methods: Twenty-one children
      with ASD aged 4-16 years (16 boys and 5 girls), after a 2-week nonwearing
      baseline period, were asked to use standard earmuffs and NC headphones for 2
      weeks, in a random order. Parents or teachers rated participants' behaviours that
      were related to their reaction to auditory stimuli. Results: Four participants
      refused to wear either the earmuffs or the NC headphones. It was found that the T
      score on the Goal Attainment Scaling was significantly higher during the earmuff
      period than that in the baseline period (Z = 2.726, p = .006). The behaviours of
      5 children with ASD improved during the NC headphone period as compared with
      those in the baseline period; there were no differences in the T-scores on the
      Goal Attainment Scaling between the NC headphone period and the baseline period
      (Z = 1.689, p = .091) and between the earmuff and NC headphone periods (Z = 
      0.451, p = .678). Conclusion: This study demonstrated the effectiveness of
      standard earmuffs and NC headphones in helping children with ASD to cope with
      problem behaviours related to hyperreactivity to auditory stimuli, therefore,
      children with ASD could use earmuffs to help to deal with unpleasant sensory
      auditory stimuli.

PMID- 30186065
TI  - Reliability and Validity of the Activity Participation Assessment for School-age
      Children in Korea.
AB  - Objective: This pilot study examined the internal consistency, test-retest
      reliability, construct validity, and discriminant validity of the Activity
      Participation Assessment (APA) for school-age children in Korea. Methods: The
      construct validity of the APA was first established by factor analysis on the
      response of 134 nondisabled children. Internal consistency was evaluated for each
      of the factors. A test-retest study was conducted on 22 nondisabled children.
      Discriminant validity was established by comparing the participation of 56
      nondisabled children and 56 children with intellectual disabilities and examining
      sex differences of 61 boys and 61 girls. Results: Analysis of the APA revealed
      five factors, which were labeled as instrumental activities of daily living
      (IADL), sports and outdoor activities, hobbies and school activities, social
      activities, and personal care. The factors showed acceptable levels of internal
      reliability (Cronbach's alpha = .63-.89). The intraclass correlation coefficient
      (ICC) for the five factors were all in the good range (ICC = .86-.92). We found
      statistically significant difference between nondisabled children and children
      with intellectual disabilities in five factors. We also found that girls
      participated in significantly more IADL, hobbies and school activities, and
      social activities. However, boys participated in significantly more sports and
      outdoor activities. Conclusion: The APA shows good internal reliability, test
      retest reliability, discriminant validity, and construct validity. However,
      evidence of psychometric properties was limited by a small sample size.
      Psychometric properties such as interrater reliability as well as concurrent
      validity and construct validity need to be tested using a larger sample size with
      representative demographics.

PMID- 30186066
TI  - Theory of Mind Deficit is Associated with Pretend Play Performance, but not
      Playfulness, in Children with Autism Spectrum Disorder.
AB  - Objective/Background: This study aimed to examine the relationships of theory of
      mind (ToM) to both pretend play and playfulness in children with autism spectrum
      disorder (ASD). Methods: Twenty children with ASD aged between 3 years and 7.11
      years were assessed with the ToM test, and then placed in a free play condition
      and a pretend play condition to assess pretend play and playfulness with the
      Child-Initiated Pretend Play Assessment and Test of Playfulness, respectively. In
      addition, the children's symptom severities of ASD and verbal abilities were also
      assessed with the Childhood Autism Rating Scale (CARS) and Receptive and
      Expressive Vocabulary Test-second edition, respectively. Results: The results of
      the regression analysis confirmed that ToM significantly predicted pretend play
      variables, namely, Number of Object Substitutions (R2 = .158, p = .002) and
      Number of Imitated Actions (R2 = .175, p = .001), but not playfulness. The CARS
      score was a significant predictor of the Percentage of Elaborate Pretend Play
      Actions of pretend play (R2 = .075, p = .034), as well as the internal control
      (R2 = .125, p = .006) and framing (R2 = .071, p = .039) variables of playfulness.
      Conclusion: The findings support the idea that children with ASD who have better
      ToM might be able to develop better pretend play, but not better playfulness,
      which might be more strongly related to their autistic severity.

PMID- 30186067
TI  - A Systematic Review on the Effect of Mechanical Stretch on Hypertrophic Scars
      after Burn Injuries.
AB  - Objective/Background: To review the effect of mechanical stretch on hypertrophic
      scars after burn injuries. Methods: A systematic review of all controlled trials
      related to the effect of mechanical stretch on post burn hypertrophic scars was
      conducted. Studies of conservative scar managements that applied mechanical
      forces parallel to the scar surface, including stretching exercise, massage, and
      splinting, were appraised. Eligible studies published in English between 1995 and
      2016 were extracted from The Cochrane Library, MEDLINE, CINAHL, Science direct,
      SPORTDiscus, and Physiotherapy Evidence Database Scale (PEDro). The journals were
      further screened with inclusion and exclusion criteria. PEDro was selected for
      further analysis and appraisal. Results: There were 853 articles identified.
      After a standardized screening mechanism stipulated, only nine full-text articles
      were selected for critical appraisal using PEDro. There were five articles of
      high quality, two of fair quality, and two of poor quality. Detailed training
      regime and outcomes of nine studies were summarised, including two studies with
      stretching exercise, six studies with massage, and one study with splinting. The
      physical parameters of scar assessments and the range of motion on affected areas
      were compared. Conclusion: From extensive literature search, there was no strong
      evidence indicating the positive effect of mechanical stretch using stretching
      exercise, massage, or splinting on hypertrophic scars. A firm conclusion cannot
      be drawn for the discrepancy of outcome measures and varied effectiveness. Most
      of the included studies lacked objective evaluation or control group for
      comparison. Further high quality studies with larger sample size and using
      standardized measurements are needed.

PMID- 30186068
TI  - Electromyographic Activity of the Upper Limb in Three Hand Function Tests.
AB  - Objective/Background: Occupational therapists usually assess hand function
      through standardised tests, however, there is no consensus on how the scores
      assigned to hand dexterity can accurately measure hand function required for
      daily activities and few studies evaluate the movement patterns of the upper
      limbs during hand function tests. This study aimed to evaluate the differences in
      muscle activation patterns during the performance of three hand dexterity tests.
      Methods: Twenty university students underwent a surface electromyographic (sEMG)
      assessment of eight upper limb muscles during the performance of the box and
      blocks test (BEST), nine-hole peg test (9HPT), and functional dexterity test
      (FDT). The description and comparison of each muscle activity during the test
      performance, gender differences, and the correlation between individual muscles'
      sEMG activity were analysed through appropriate statistics. Results: Increased
      activity of proximal muscles was found during the performance of BEST (p < .001).
      While a higher activation of the distal muscles occurred during the FDT and 9HPT
      performance, no differences were found between them. Comparisons of the sEMG
      activity revealed a significant increase in the muscle activation among women (p
      = .05). Strong and positive correlations (r > .5; p < .05) were observed between
      proximal and distal sEMG activities, suggesting a coordinate pattern of muscle
      activation during hand function tests. Conclusion: The results suggested the
      existence of differences in the muscle activation pattern during the performance
      of hand function evaluations. Occupational therapists should be aware of unique
      muscle requirements and its impact on the results of dexterity tests during hand
      function evaluation.

PMID- 30186069
TI  - Leisure-time Physical Activity of Polish White-collar Workers: A Cross-sectional
      Study.
AB  - Objective/Background: The aim of this study was to assess the leisure-time
      physical activity of Polish white-collar workers in relation to various health
      recommendations. Methods: The study used a cross-sectional design with a
      convenience sample of 482 white-collar workers from Poland. Researchers recorded
      the leisure-time physical activity logs for 7 consecutive days of the week.
      Physical activity level was interpreted in relation to the World Health
      Organization and the American College of Sports Medicine recommendations.
      Results: Among the workers, 42% of women and 53% of men declared moderate
      physical activity for at least 150 minutes per week, but only 23% of women and
      18% men undertook activity in at least 5 days. Conclusion: The results of the
      physical activity identified were significantly different from the American
      College of Sports Medicine and World Health Organization recommendations. The
      lower percentage of workers who met American College of Sports Medicine
      recommendations was caused by insufficient frequency of physical efforts.

PMID- 30186070
TI  - An Ecological Framework to Support Small-Scale Shared Housing for Persons with
      Neurocognitive Disorders of the Alzheimer's and Related Types: A Literature
      Review.
AB  - Background: Small scale shared housing arrangements (SHAs) is a
      deinstitutionalized model of care designed to resemble a typical home of <10
      people and are increasingly available for persons with neurocognitive disorders
      of the Alzheimer's and related types (NCD). However, there is little aggregate
      evidence of their effect on persons with NCD thus, a literature review was
      performed. Methods: Database searches were conducted across CINAHL Complete,
      OTseeker, PubMed, Ovid, Academic One File, ProQuest Nursing and Allied Health,
      the World Wide Web and Google Scholar using the several key words that included
      neurocognitive disorders, Alzheimer's, dementia, quality of life, well-being,
      occupational performance, activities of daily living, small scale shared housing,
      sheltered housing and group homes. Bibliographic references from final articles
      were also examined. Selection criteria involved three steps: screening
      perspective articles by title and abstract, assessing full text for eligibility
      and finally, reviewing full-texts. Results: 16 studies were selected for final
      review where most found the association of SHAs with various occupational
      performance indicators unique to the NCD population better than or equal to
      controls (traditional models of long term care). A small minority of studies had
      mixed or inconclusive results. No study found SHAs necessarily worse than
      controls. Conclusion: The SHA model has many benefits for person's with NCD and
      may be especially advantageous for those in the early stages of the disease
      process. The occupational therapy profession should continue to raise awareness
      of SHAs and consider ecological theory as a valid basis for their expansion.

PMID- 30186071
TI  - Application of the Korean Version of the Modified Barthel Index: Development of a
      keyform for use in Clinical Practice.
AB  - Objective: To demonstrate the clinical application of the Korean version of the
      Modified Barthel Index (K-MBI) using Rasch analysis. Methods: A total of 276
      patients with neurological disorders were assessed with the K-MBI in outpatient
      clinics. The Rasch partial-credit model was used to generate a keyform based on
      investigating the psychometric properties of the K-MBI, including dimensionality,
      precision (person strata and reliability), and hierarchical item difficulty. The
      Minimal Detectable Change (MDC) in item difficulty was used to establish right
      challenging treatment goals and long-term treatment plans. Results: The findings
      demonstrated that the Korean version of the MBI satisfied the assumption of
      unidimensionality. It also showed a hierarchical structure in terms of item
      difficulty, good reliability (Cronbach alpha, 0.92), and approximately five
      distinct person strata (4.6). The MDC (raw score, 20.1) of the item difficulty of
      the test items demonstrated equivalent cutoff scores for targeted short-term
      treatment goals on the keyform, a Rasch-derived display of patient responses.
      Long-term treatment goals were identified based on the test items of the keyform.
      Conclusions: The findings suggest that a Rasch keyform can be applied to clinical
      practice in Korean settings by identifying clinically and statistically
      meaningful test items and their step thresholds as short- and long-term goals.

PMID- 30186072
TI  - Leisure Time Physical Activity among Employed and Unemployed Women in Poland.
AB  - Objective/Background: The aim of the paper was to investigate the leisure time
      physical activity (LTPA) among Polish employed and unemployed women in light of
      meeting the World Health Organisation (WHO) recommendations and analysed its
      relationship with employment status. The concept of personal responsibility for a
      healthy lifestyle plays in the modern times a crucial role here and is an
      integral part of the prevention process (including the necessity for LTPA).
      Methods: A sample (n = 527) of Polish women was surveyed by the long form of
      International Physical Activity Questionnaire (IPAQ-LF), with statistically
      significant differences between variables (intensity and duration of the activity
      vs. employment status), in the model being verified by chi-square testing. Multi
      variable logistic regression analysis was performed to find the relationship
      between socio-demographic criteria and the amount of exercise recommended by WHO.
      The relationship between LTPA and the amount of exercise recommended by WHO was
      assessed using the log-linear analysis. Results: Over one-third of the
      respondents did not engage in any LTPA (employed -- 38.6 and unemployed --
      36.6%). Employed women engaged in vigorous exercises more often (18.2%) than
      those who were unemployed (5.8%). The amount of LTPA undertaken by the majority
      of respondents (58.7% employed and 65.2% unemployed) was not sufficient to
      maintain their health owing to lack of walking, moderate and vigorous LTPA.
      Conclusion: Polish women nowadays (regardless of whether they are employed or
      not) still do not engage in a sufficient amount of LTPA to maintain their health.
      Intervention programme in both groups is needed.

PMID- 30186073
TI  - Article Commentary: A Psychospiritual Integration frame of Reference for
      Occupational Therapy. Part 2: Transformative Occupations and the Change Process.
AB  - This paper builds upon the first in the series on psychospiritual integration
      (PSI) and examines the concept of transformative occupations and the process of
      change underpinning occupational therapy from a PSI perspective. A repertoire of
      new terms highlighting finer distinctions in the concept of occupation will be
      introduced and explained, as will the dynamic for transformation inherent in the
      psychospiritual integration change process. Suggestions for PSI-informed
      occupational therapy practice will be explored.

PMID- 30186074
TI  - Effects of an Oral-Pharyngeal Motor Training Programme on Children with
      Obstructive Sleep Apnea Syndrome in Hong Kong: A Retrospective Pilot Study.
AB  - Background: This study aimed to investigate the effects of an oropharyngeal motor
      training programme on children with Obstructive Sleep Apnea Syndrome (OSAS) in
      Hong Kong. Methods: In this retrospective study, we reviewed the outcomes of 10
      children with OSAS who had received an oropharyngeal motor training programme in
      Occupational Therapy Department of an acute hospital in Hong Kong over a 1-year
      programme. Each participant attended an individual oropharyngeal motor training
      programme plus a follow-up session after 2 months. The training programme
      consisted of 10 individual mobilization exercises involving the orofacial and
      pharyngeal area for 45 minutes. Each exercise had to be repeated for 10 times.
      Three outcome measures were chosen to study the effectiveness of the training
      programme including tongue strength, tongue endurance level and orofacial
      function. Tongue strength and tongue endurance level were assessed using the Iowa
      Oral Pressure Instrument (IOPI). The Nordic Orofacial Test-Screening (NOT-S)
      Assessment was used to assess the orofacial function. Seven out of 10
      participants completed the training programme and attended the follow-up session
      after two months. Results: The tongue strength and the scores of NOT-S of the 7
      participants were found to have significant improvement after training. However,
      there was no significant difference in tongue endurance level. Conclusion: The
      findings of this study support the role of occupational therapist in oromotor
      training modalities to improve the respiratory function for children with OSAS in
      Hong Kong. Copyright (c) 2017, Hong Kong Occupational Therapy Association.
      Published by Elsevier (Singapore) Pte Ltd. This is an open access article under
      the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

PMID- 30186075
TI  - Factors Affecting Mortality and Hospital Admissions after Hip Surgery among
      Elderly Patients with Hip Fracture in Hong Kong - Review of a Three-Year Follow
      Up.
AB  - Objective: Hip fracture is associated with excess mortalities and high rate of
      hospital re-admission after discharge from the indexed episode. To improve
      related post-discharge care, we aimed to find out characteristics that were
      associated with related higher rates of mortality and hospital re-admission.
      Methods: This was a historical cohort study with following up of 273 patients
      recruited in a local rehabilitation hospital for 3 years. The outcome of interest
      was cumulative mortalities and hospital re-admissions in the 1st 3 years after
      their discharge from the rehabilitation hospital. These outcomes were collected
      in the hospital data warehouse - the Clinical Data Analysis and Reporting System
      (CDARS). Eighteen predictors, as proposed by similar studies and our own review,
      were retrieved from our standard clinical forms as well as from the CDARS. Binary
      logistic regression was used to test their association with the outcomes and to
      generate the respective odd ratios. Results: The cumulative overall mortality
      rates at 0.5-, 1-, 2- and 3- year after hip fracture were 7.2%, 14.0%, 24.6% and
      33.4% respectively, while the cumulative "1st ever hospital read-mission" at 0.5
      , 1, 2- and 3- years after hip fracture were 29.4%, 41.6%, 59.4% and 71.7%
      respectively. The most significant predictors i) for mortality at 3- year were:
      "Being male" (OR 5.33), "Delayed surgery >48 hours" (OR 2.65), "pre-operation
      albumin level <3.5 g/dl" (OR 2.66), and, ii) for "1st ever hospital readmission"
      at 0.5-year was "Being Assisted walker or non-walker (after rehabilitation)" (OR
      3.83). Conclusions: Characteristics that define the groups of patients with hip
      fractures with higher mortality and rate of hospital re-admission were
      identified. This could help healthcare professionals to focus on target patient
      groups for closer monitoring and more intensive post-discharge care.

PMID- 30186076
TI  - Effect of Passive Limb Activation by Functional Electrical Stimulation on
      Wheelchair Driving in Patients with Unilateral Spatial Neglect: A Case Study.
AB  - Background/Objective: Limb activation is one of the behavioural interventions to
      improve unilateral spatial neglect (USN). However, the effect of passive limb
      activation on activities of daily living (ADL) is not clear. This study examined
      the effect of passive limb activation by functional electrical stimulation (FES)
      on wheelchair driving for patients with USN, and to discuss the possibility of
      application of this treatment to occupational therapy. Methods: A single subject
      design-baseline-intervention-baseline (ABA), was applied to 2 stroke patients
      with USN. Phase A' and A consisted of the wheelchair driving task only. Phase B
      consisted of the wheelchair driving task with FES. Each phase lasted for 2 weeks.
      The wheelchair driving task was maneuvering on a square passage in the clockwise
      and counter clockwise conditions for 8 minutes respectively, and four obstacles
      were set at each side. FES was applied to the affected forearm extensor muscles.
      Assessor recorded: 1) The distance participants drove wheelchair for 8 minutes,
      and 2) The number of collisions with obstacles and the wall, for 10 days.
      Results: For one participant, the distance of maneuvering significantly increased
      in phase B (p < .05.), and USN on the cognitive test in the extrapersonal space
      indicated a tendency to improve after phase B. Conclusion: Passive limb
      activation by FES improved wheelchair driving and cognitive performance for
      patients with USN. It can be used with instruction from occupational therapists
      to enhance the performance on ADL.

PMID- 30186077
TI  - Development of an Intervention Programme for Selective Eating in Children with
      Autism Spectrum Disorder.
AB  - Objective/Background: Most parents of children with autism spectrum disorder
      (ASD) have difficulties with the selective eating behaviour of their children.
      This study aimed to develop a newly designed intervention programme on improving
      selective eating behaviour for parents of children with ASD and evaluate its
      effectiveness. Methods: The participants were 23 parents of children (aged 3-6
      years) with ASD. The education programme included a session that addressed
      approaches to improve selective eating and attitudes at meal times, with a
      discussion. The intervention aimed to identify the underlying factors and
      approaches to improve selective eating in children and the self-efficacy of
      parents. Results: Significant differences were observed before and after the
      intervention in the degree of difficulty perceived by parents, their degree of
      self-efficacy, the number of recommendations conducted by them, their subjective
      view of the degree of dietary imbalance, and the number of food items consumed by
      their children. Conclusion: We developed an interventional programme for parents
      of children with ASD and this programme was found to be useful. It is important
      for occupational therapists to consider the factors and approaches for selective
      eating in children with ASD in order to provide early intervention for their
      parents.

PMID- 30186079
TI  - Work Motivation among Occupational Therapy Graduates in Malaysia.
AB  - Objective/Background: Occupational therapy that focuses on servicing clients
      demands motivated workers for quality service delivery. The objectives of this
      study were: (a) to determine the level of work motivation among occupational
      therapy graduates in Malaysia and (b) to determine if there is a difference in
      work motivation among these graduates based on work sector, job position, length
      of work experience, and gender. Methods: This cross-sectional study recruited
      occupational therapy bachelor's degree graduates using an online survey. The Work
      Extrinsic and Intrinsic Motivation Scale (WEIMS) was used to measure level of
      work motivation. Results: Responses from 82 (60.3%) graduates (male: 26.8%;
      female: 73.2%) were analysed. Sixty-two (75.6%) graduates worked locally and 20
      (24.4%) worked in foreign countries. The average Work Self-Determination Index (W
      SDI) score for WEIMS is +11.38 with 78 (95.1%) of graduates demonstrated a self
      determined motivational profile and 4 (4.9%) demonstrated a nonself-determined
      profile. Graduates in the private sector (13.10 +/- 6.47) show significantly
      higher W-SDI score compared to those in the public sector (9.40 +/- 6.06), p =
      0.01. W-SDI scores appeared higher among clinician (11.67 +/- 6.40), case manager
      (13.33), and others (14.90 +/- 8.23); and those with work experience of 5-6 years
      (13.11 +/- 6.90) and less than one year (12.65 +/- 7.12). Male (10.29 +/- 6.86)
      and female (11.79 +/- 6.39) graduates shared equally high score. There is no
      significant difference in W-SDI score based on job position, length of work
      experience, and gender. Conclusion: Occupational therapy graduates have high work
      motivation as evident by their self-determined profile. Only work sector imposes
      difference in work motivation among these graduates. Copyright (c) 2017, Hong
      Kong Occupational Therapy Association. Published by Elsevier (Singapore) Pte Ltd.
      This is an open access article under the CC BY-NC-ND license
      (http://creativecommons.org/licenses/by-nc-nd/4.0/).

PMID- 30186078
TI  - The Effectiveness of Mindfulness-Based Intervention in Attention on Individuals
      with ADHD: A Systematic Review.
AB  - Background/Objective: Mindfulness-based intervention has received more clinical
      interest and empirical support for individuals with ADHD especially to improve
      attention. However, no systematic review has been done to analyze and compare the
      effectiveness of mindfulness-based intervention on individuals with ADHD in
      different age groups. This review examined its effectiveness for individuals
      (children, adolescents and adults) with ADHD to improve attention. Methods: In 7
      databases, totally of 152 studies were identified; 9 met the inclusion and
      exclusion criteria and were reviewed. Five of the studies recruited adults as the
      participants, two recruited adolescents as the participants, one recruited both
      adults and adolescents as the participants and one recruited children as the
      participants. Results: It was found that mindfulness-based intervention was
      comparatively more popularly used in adults with ADHD to improve attention, and
      the improvement was significant. Conclusion: It is still unclear whether
      mindfulness-based intervention is effective for children and adolescence with
      ADHD due to limited studies available and the limitations of the study design in
      the reviewed studies. Therefore, more research in the future is required to
      answer the question.

PMID- 30186080
TI  - Relationship between Motor Coordination, Cognitive Abilities, and Academic
      Achievement in Japanese Children with Neurodevelopmental Disorders.
AB  - Background/Objective: Motor coordination impairment is common in children with
      neurodevelopmental disorders such as autism spectrum disorder (ASD) and attention
      deficit/hyperactivity disorder (AD/HD). The purpose of this study was to
      investigate the relationship between motor coordination, cognitive ability, and
      academic achievement in Japanese children with neurodevelopmental disorders.
      Methods: Thirty-four school-age (6-12 years old) children with neurodevelopmental
      disorders and 34 age-matched typically developing (TD) children were recruited in
      this study. Correlations between the scores of the Movement Assessment Battery
      for Children-2 (M-ABC2) and the Kaufman Assessment Battery for Children - Second
      Edition (K-ABCII) that assesses cognitive abilities, and academic achievement
      were analyzed. Results: The children with neurodevelopmental disorders obtained a
      lower total score and all component scores on M-ABC2 compared to the TD children.
      In children with neurodevelopmental disorders, M-ABC2 Manual Dexterity score was
      significantly correlated with K-ABCII Simultaneous Processing (r = .345, p =
      .046), Knowledge (r = .422, p = .013), Reading (r = .342, p = .048), Writing (r =
      .414, p = .017), and Arithmetic (r = .443, p = .009) scores. In addition, M-ABC2
      Balance score was significantly correlated with K-ABCII Learning (r = .341, p =
      .048), Writing (r = .493, p = .004), and Arithmetic (r = .386, p = .024) scores.
      Conclusion: These findings stress that it is essential to accurately identify
      motor coordination impairments and the interventions that would consider motor
      coordination problems related to cognitive abilities and academic achievement in
      Japanese children with neurodevelopmental disorders.

PMID- 30186082
TI  - Development of the Japanese version of the Westmead Home Safety Assessment for
      the elderly in Japan.
AB  - Objective: Home safety assessment and intervention is a key component in the
      management of fall risk in elderly people. However, a standardised assessment for
      home safety has not yet been established in Japan. We developed a Japanese
      version of the Westmead Home Safety Assessment by partially modifying the
      original version according to house structures and lifestyles in Japan and
      examined its inter-rater reliability and content validity. Methods: Japanese
      elderly in the community who had fear of falls were recruited to investigate the
      reliability of the Japanese version of the Westmead Home Safety Assessment. Two
      occupational therapists simultaneously visited a participant's home to perform
      the Japanese version of the Westmead Home Safety Assessment independently.
      Further, an expert panel of 18 occupational therapists evaluated the relevance of
      each item of the Japanese version of the Westmead Home Safety Assessment.
      Results: Fifty elderly people (aged 78.2 +/- 7.1 years) participated in this
      reliability study. The most frequent hazards were identified as internal
      steps/stairs, seating, bathroom, bath, and external steps/stairs. Forty-nine
      items (69%) in the Japanese version of the Westmead Home Safety Assessment were
      rated to have fair to good (0.40 < kappa < 0.75) or excellent (kappa >= 0.75)
      reliability as well as excellent validity (item content validity >=0.78). These
      items were concerned with basic activities of daily living and some simple
      instrumental activities of daily living. The scale content validity was 0.78 +/-
      0.16 but was not excellent (scale content validity index <0.90). Conclusions:
      This study suggested that 49 items in the Japanese version of the Westmead Home
      Safety Assessment were appropriate for home safety assessment for Japanese
      elderly. Further research is necessary to improve the reliability and validity of
      the present version of the Japanese version of the Westmead Home Safety
      Assessment for this population.

PMID- 30186081
TI  - Orthotic management of fixed flexion deformity of the proximal interphalangeal
      joint following traumatic injury: A systematic review.
AB  - Background/objective: Fixed flexion deformity of the proximal interphalangeal
      joint can commonly occur following a traumatic injury impacting on hand function
      and occupational performance. Numerous interventions have been proposed for fixed
      flexion deformity resolution. This paper investigates the efficacy of static or
      dynamic orthoses in reducing fixed flexion deformity contracture following
      traumatic proximal interphalangeal joint injury. Methods: A multi-database search
      of three databases (CINAHL, EMBASE, MEDLINE) was conducted. Data extracted for
      each study were design, patient descriptions, degree of fixed flexion deformity
      pre- and post-orthoses, and prescribed interventions and exercise programmes.
      Results: The search yielded 643 studies, of which eight met the inclusion
      criteria. Studies used heterogeneous methodologies investigating various orthotic
      interventions. Meta-analysis or pooling of results was not possible. Dissimilar
      orthotic wear regimes were noted in all studies and an alternative clinical
      significance outcome was found. Conclusion: More research is required to support
      clinical reasoning in orthotic choice for fixed flexion deformity of the proximal
      interphalangeal joint post-traumatic injury.

PMID- 30186083
TI  - Effects of object size and distance on reaching kinematics in patients with
      schizophrenia.
AB  - Background/Objective: Patients with schizophrenia not only have psychiatric
      symptoms, but also have movement problems, which might also be associated with
      their reduced quality of life. Little is known about how to improve their
      movement performance for patients. Manipulating object size and distance is
      common in occupational therapy practice to evaluate and optimize reaching
      performance in patients with physical disabilities, but effects of the
      manipulation in patients with schizophrenia remain unclear. The purpose of this
      study was to examine whether object size and distance could change performance of
      reaching kinematics in patients with mild schizophrenia. Methods: Twenty-nine
      patients with mild schizophrenia and 15 age- and gender-matched healthy controls
      were required to reach for, as quickly as possible, a small or large object that
      was placed at a near or far distance. We measured movement time, peak velocity,
      path length ratio, percentage of time to peak velocity, and movement units to
      infer movement speed, forcefulness, spatial efficiency (directness), control
      strategies, and smoothness. Results: Patients' reaching movements were slower (p
      = .017) and less direct (p = .007) than those of controls. A larger object
      induced faster (p = .016), more preprogrammed (p = .018), and more forceful (p =
      .010) movements in patients. A farther object induced slower, more feedback
      dependent, but more forceful and more direct movements (all p < .001).
      Conclusion: The results of kinematic deficiencies suggest the need of movement
      training for patients with mild schizophrenia. Occupational therapists may grade
      or adapt reaching activities by changing object size and distance to enhance
      movement performance in patients with schizophrenia.

PMID- 30186084
TI  - Use of parametric speaker for older people with dementia in a residential care
      setting: A preliminary study of two cases.
AB  - Objective/Background: Older people with dementia often show behavioural and
      psychological symptoms of dementia such as agitation, aggression, and depression
      that affect their activities of daily living, and hence reduce the quality of
      life of their caregivers. The aim of this study was to investigate the effects of
      a new technological intervention-a parametric speaker, creating a narrow personal
      acoustic environment, which may reduce the manifestation of behavioural and
      psychological symptoms of dementia symptoms. Methods: A parametric speaker was
      placed on the ceiling of a large day room, and personally selected pieces of
      music were provided in a narrow space just under the speaker during the
      intervention. Two older residents with behavioural and psychological symptoms of
      dementia participated in the experiment. Results: Playing pieces of favorite
      music via the parametric speaker decreased their behavioural and psychological
      symptoms of dementia during the intervention. In addition, this intervention
      reduced the burden on caregivers. One of the advantages of using parametric
      speaker was being able to create a personal space in a common room. Conclusion:
      We considered that the parametric speaker might be useful to reduce behavioural
      and psychological symptoms of dementia and the burden on caregivers, providing
      individualized rehabilitation for the improved quality of life of residents.

PMID- 30186085
TI  - Engaging persons with disabilities as community teachers for experiential
      learning in occupational therapy education.
AB  - Background: Cultivating empathy towards persons with disabilities has been
      highlighted as an essential graduate attribute in the occupational therapy
      profession. Purpose: With the aim to developing a more holistic understanding of
      disability, this project seeks to translate an experiential learning activity
      developed in Canada to the local Singaporean context. Small groups of two to
      three students were paired with a person with physical disability, known as a
      community teacher, for a series of visits to observe and participate in their
      self-care, productivity and leisure activities. Method: A sequential explanatory
      mixed methods design was adopted with the administration of an adapted version of
      the Multidimensional Attitudes Scale Towards Persons with Disabilities on 51
      first year occupational therapy students. Seventeen students participated in
      three focus group discussions at the end of the learning activity.Findings:
      Comparison of pre- and post-scores using Wilcoxon signed-rank tests of all three
      subscales of the Multidimensional Attitudes Scale Towards Persons with
      Disabilities yielded significant improvements. The average score for Affect
      improved from 42.94 to 32.08, z = -5.43, P <  .001; for Cognition improved from
      26.12 to 21.41, z = -4.20, P <  .001; for Behaviour improved from 23.78 to 20.65,
      z= -4.44, P <  .001. Effect sizes ranged from medium to large. Thematic analysis
      of focus groups led to the identification of four themes that explained these
      improvements.Implications: Experiential learning can be effective in cultivating
      empathy and improving attitudes of occupational therapy students towards persons
      with disabilities. There is potential to expand this pedagogical approach to
      other health sciences disciplines.

PMID- 30186086
TI  - Influence of functional mobility and manual function on play in preschool
      children with cerebral palsy.
AB  - Introduction: This study analysed the differences in play performance between
      preschool children with cerebral palsy and those with typical development and
      investigated the factors influencing functional mobility and manual dexterity on
      play in children with cerebral palsy. Method: Sixty preschool children (30 with
      cerebral palsy; 30 with typical development), were assessed by the revised Knox
      Preschool Play Scale, being that children with cerebral palsy were also
      classified according to their functional mobility and manual dexterity. Results:
      On average, all measures were significantly smaller in the cerebral palsy group
      than the typical development group (p<= .002). Manual function and functional
      mobility were negatively correlated with material (r = -.456, p = .011; r = 
      .487, p = .006) and space (r = -.494, p = .006; r = -.784, p = .000). Also the
      results pointed out a significant correlation with topography and manual function
      (r = .404, p = .027) and functional mobility (r = .718, p = .000). Pretend play
      and participation showed no correlation with topography (r = -.051, p = .788; r =
      -.312, p = .093), manual function (r = -.019, p = .921; r = -.322, p = .083) and
      functional mobility (r = -.085, p = .657; r = -.308, p = .097). Conclusion: Play
      performance of children with typical development was superior to those with
      cerebral palsy. The degree of impairment of functional mobility and manual
      function negatively was negatively associated with play exploration but did not
      relate to pretend play or social interaction in play.

PMID- 30186087
TI  - Riksmaten Adolescents 2016-17: A national dietary survey in Sweden - design,
      methods, and participation.
AB  - Background: Nationally representative information on food consumption data is
      essential to evaluate dietary habits, inform policy-making and nutritional
      guidelines, as well as forming a basis for risk assessment and identification of
      risk groups. Objective: To describe the methods used in the Swedish national
      dietary survey of adolescents, Riksmaten Adolescents 2016-2017. Design: Students
      in grades 5, 8, and 11 (mean ages 12, 15, and 18 years) were recruited in this
      school-based cross-sectional survey. A new, validated, web-based method was used
      to assess dietary intake. Information on physical activity, health, and
      socioeconomic background was collected through web questionnaires. Physical
      activity was also evaluated by accelerometers. Weight and height were measured in
      all participants, while blood and urine samples were collected in a subsample of
      40% of the participants. Results: A total of 3,477 (68%) respondents participated
      and 3,099 (60%) had complete dietary information. In the subsample, 1,305 (55%)
      respondents participated and 1,105 (46%) had complete dietary information. The
      participants were overall representative for the population with regard to
      socioeconomic background and school organization (public or independent). All
      types of municipalities were represented in the survey and overall, the
      geographic distribution corresponded to the underlying population. Some
      differences by school grade were observed. Sample weights were calculated for the
      total sample and the subsample. Conclusion: The Riksmaten Adolescents 2016-2017
      provides valuable national data on diet, physical activity, and markers of
      exposure in age groups where data have been lacking. The data will provide a
      valuable basis for risk assessment, public health policy, and in-depth analyses.

PMID- 30186088
TI  - Recurrent Mantle Cell Lymphoma Presenting as Gastrointestinal Bleeding.
AB  - Mantle cell lymphoma is a rare and aggressive subtype of B-cell non-Hodgkin
      lymphomas. Mantle cell lymphoma frequently involves extranodal sites, and
      gastrointestinal tract is involved microscopically and macroscopically in more
      than 80$ of cases. We present two cases of recurrent mantle cell lymphoma
      presenting with lower and upper gastrointestinal bleeding, respectively. A 58
      year-old woman with a history of recurrent mantle cell lymphoma treated with
      chemotherapy and stem cell transplantation presented with left-sided abdominal
      pain and hematochezia. Colonoscopy showed a mass-like lesion in the ascending
      colon, polyps in the ascending colon, and splenic flexure. A 68-year-old man with
      a history of mantle cell lymphoma treated with chemotherapy presented with
      epigastric pain and melena. Esophagogastroduodenoscopy showed a large polypoidal
      ulcerated mass with oozing in the duodenal bulb. Biopsies in both patients were
      suggestive of mantle cell lymphoma. Patients with mantle cell lymphoma could be
      asymptomatic or may present with abdominal pain, obstruction, diarrhea, or
      gastrointestinal bleeding. In patients presenting with gastrointestinal symptoms,
      endoscopy must be pursued and biopsies must be taken for any suspicious lesions
      as well as normal mucosa to exclude mantle cell lymphoma as an etiology for the
      lesion or symptoms. Even though there are no standard guidelines for endoscopic
      screening of gastrointestinal tract in asymptomatic patients, one should be aware
      of involvement of gastrointestinal tract in the early course of disease or
      recurrent disease. Although mantle cell lymphoma is initially responsive to
      chemotherapy, it eventually becomes refractory with a median survival of 3-5
      years.

PMID- 30186089
TI  - A Case of Successful Treatment of Ruptured Pancreaticoduodenal Artery Aneurysm
      Caused by Celiac Artery Dissection.
AB  - A 52-year-old man was admitted due to severe epigastric lesion pain. Esophagus
      gastroduodenal endoscopy showed impaired duodenal dilatation, and contrast
      enhanced computed tomography revealed a pancreaticoduodenal artery (PDA) aneurysm
      13 mm in diameter below the head of the pancreas, retroperitoneal hematoma,
      idiopathic celiac artery (CA) dissection, and common hepatic artery disruption.
      Angiographic embolization with a mixture of N-butyl-1,2-cyanoacrylate and
      lipiodol was performed, and follow-up study showed improvement of the dilatation
      of the duodenum and disappearance of the aneurysm. Here we report a quite rare
      case of PDA aneurysm by idiopathic dissection of CA treated successfully with
      angiographic embolization.

PMID- 30186090
TI  - Adenocarcinoma Arising from Perianal Fistulizing Crohn's Disease.
AB  - Perianal fistula is a very debilitating event and a cause of morbidity in
      patients with Crohn's disease (CD). Its malignant transformation is very rare
      with an incidence of around 0.004-0.7$. Presence of disease in the colon and
      rectum is the major risk factor for the development of a perianal fistula. In
      this report we show a case of adenocarcinoma arising from a perianal fistulizing
      CD. This type of tumor is highly aggressive, difficult to diagnose, and has a
      rather poor prognosis. The different neoplastic transformations and the different
      types of tumors that may appear in patients with CD, especially at the colorectal
      level or at the level of an eventual anastomosis, are to date well documented and
      described in the literature, while there is a lack of information and of treated
      cases concerning the occurrence of cancer at the level of a fistula. Due to the
      rarity of cases, we tried to identify the most frequent and important risk
      factors: sex, duration of disease, age at diagnosis, and the history of the
      fistula.

PMID- 30186091
TI  - Primary Mesenteric Carcinoid Tumor Presenting with Carcinoid Syndrome.
AB  - Neuroendocrine neoplasms (NENs) are a diverse group of tumors arising throughout
      the body with a common origin from neuroendocrine cells. Well-differentiated
      NENs, also known as neuroendocrine tumors (NETs), are generally indolent and are
      often found incidentally, while poorly differentiated tumors are more aggressive.
      Carcinoid tumors are NETs arising from the gastrointestinal tract and less
      commonly from the lungs, thymus, and kidneys. NETs in the mesentery arise from
      metastasis from primary tumor, and carcinoid syndrome in this setting results
      from concomitant metastasis to the liver. Primary mesenteric carcinoid tumors are
      very rare. We present a 64-year-old man with carcinoid syndrome from a mesenteric
      carcinoid tumor without evidence of liver metastasis or other primary tumor
      sites.

PMID- 30186092
TI  - The Feature of Solitary Small Nodular Type of Hepatic Epithelioid
      Hemangioendothelioma.
AB  - Hepatic epithelioid hemangioendothelioma (HEHE) is a rare tumor. Preoperative
      diagnosis of HEHE is difficult because it does not manifest specific symptoms or
      tumor markers. We report a resected case of small and solitary HEHE. The patient,
      a 74-year-old man, had undergone surgical resection for left renal cell carcinoma
      20 years ago. During follow-up, a tumor approximately 1.3 cm in diameter was
      detected by computed tomography (CT) at liver segment VIII. It showed isodensity
      in the arterial phase, low density in the portal venous phase, and homogeneous
      enhancement in the late phase on CT and magnetic resonance imaging (MRI). We
      performed hepatic resection of the right hepatic vein drainage area. A
      pathological diagnosis of HEHE was made. Although small and solitary HEHE is
      rare, an enhancement pattern in each phase on CT and MRI, using contrast media,
      can yield clues for the diagnosis of HEHE.

PMID- 30186093
TI  - Spontaneous Regression of Hepatocellular Carcinoma with Portal Vein Tumor
      Thrombus.
AB  - An 83-year-old man underwent transcatheter arterial chemoembolization (TACE) for
      a 20-mm hepatocellular carcinoma (HCC) in Couinaud's segment 4. Computed
      tomography (CT) 4 months after TACE showed tumor thrombus in the portal vein in
      addition to diffuse metastases and arterioportal shunts in the left lobe.
      Although we performed the best supportive care, the tumor thrombus in the portal
      vein and tumors in the left lobe had completely disappeared on CT 16 months after
      the TACE. Rapidly grown portal vein tumor thrombus and arterioportal shunt might
      be the causes of spontaneous regression of HCC, probably associated with tumor
      hypoxia.

PMID- 30186094
TI  - An Unusual Cause of Abdominal Ascites.
AB  - Abdominal ascites is most commonly caused by portal hypertension from liver
      cirrhosis. When present, portal hypertension is associated with an elevated serum
      ascites albumin gradient (SAAG) >=1.1 g/dL. In contrast, a SAAG < 1.1 g/dL
      suggests malignancy, tuberculosis, pancreatitis, or nephrotic syndrome. Here, we
      present a case of low SAAG ascites caused by epithelioid peritoneal mesothelioma
      in a woman with no known liver disease. The diagnosis proved elusive until
      diagnostic laparoscopy with biopsy was performed.

PMID- 30186095
TI  - Difficulty Achieving a Preoperative Diagnosis of IgG4-Related Sclerosing
      Cholangitis.
AB  - A 75-year-old male was admitted to our hospital because of bile duct stenosis. He
      had no medical history of autoimmune disease. The level of tumor markers, serum
      IgG, and IgG4 were within normal ranges. Computed tomography showed perihilar and
      distal bile duct stenosis and wall thickening without swelling or abnormal
      enhancement of the pancreas. Endoscopic retrograde cholangiopancreatography
      showed perihilar and distal bile duct stenosis. A biopsy and cytology from the
      distal bile duct stenosis suggested adenocarcinoma, and cytology from the
      perihilar bile duct also suggested adenocarcinoma. A preoperative diagnosis of
      perihilar and distal bile duct cancer was made, and the patient underwent left
      hepatectomy and pancreaticoduodenectomy. Resected specimens showed wall
      thickening in the perihilar and distal bile duct; however, tumors were unclear. A
      histopathological examination revealed lymphoplasmacytic infiltration, storiform
      fibrosis, and obliterative phlebitis in the perihilar and distal bile ducts.
      Immunohistochemistry revealed diffuse infiltration of IgG4-positive plasma cells
      in the perihilar and distal bile ducts. Lymphoplasmacytic infiltration,
      inflammatory change, storiform fibrosis, and obliterative phlebitis were shown in
      the pancreas. A final diagnosis of IgG4-related sclerosing cholangitis (IgG4-SC)
      with autoimmune pancreatitis was made. We herein report a case in which a
      preoperative diagnosis of IgG4-SC was difficult due to normal serum IgG4 levels
      and no obvious pancreatic lesion.

PMID- 30186096
TI  - Pneumatosis Cystoides Intestinalis Secondary to Sunitinib Treatment for
      Gastrointestinal Stromal Tumor.
AB  - A 67-year-old man with liver and retroperitoneal metastases from a
      gastrointestinal stromal tumor arising in the jejunum had been administered oral
      sunitinib for 2 months. He presented to our department with right-sided lower
      abdominal pain. His general condition was good, with no high-grade fever, and the
      other vital signs were also stable. Contrast-enhanced computed tomography was
      promptly performed, and pneumatosis cystoides intestinalis (PCI) was detected in
      a wide area around the ileocecal lesion. There were no signs of acute abdomen
      requiring emergency surgery due to conditions such as intestinal perforation,
      ischemia, or obstruction. Sunitinib was discontinued and the patient was placed
      on nil orally with intravenous infusion. PCI resolved promptly and the patient
      was discharged on the 21st day after admission. PCI is a rare side effect of
      sunitinib with only 8 cases reported previously, which can complicate with acute
      abdomen or gastrointestinal perforation, in some cases. Thus, the early
      identification of sunitinib as the cause of PCI is important. Although PCI is a
      rare adverse effect of sunitinib, clinicians must be aware of it to promptly
      provide the correct diagnosis and treatment.

PMID- 30186097
TI  - Ginseng-Related Drug-Induced Liver Injury.
AB  - Ginseng is commonly used as a medicinal herb for memory and concentration and
      general well-being. Drug-induced liver injury (DILI) is one of the most
      challenging disorders and trending events in the United States which are related
      to body building and weight loss supplements. Currently, herbal and dietary
      supplementation is the second most common cause of DILI. Here, we report on a 45
      year-old healthy Chinese woman who presented with dull intermittent left upper
      quadrant abdomen pain for a month. Upon thorough history taking, she had been
      taking ginseng tea and supplementation for her menopausal symptoms for almost 3
      months. Physical examination was unremarkable except mild tenderness in left
      upper quadrant of the abdomen. Liver function test showed aspartate transaminase
      (AST) 717 U/L, alanine transaminase (ALT) 343 U/L, total bilirubin 5 mg/dL,
      direct bilirubin 3.3 mg/dL, alkaline phosphatase 182 U/L, with international
      normalized ratio (INR) 1.2. Prior liver enzymes (6 months earlier) showed AST 21
      U/L, ALT 18 U/L, total bilirubin 0.8 mg/dL, direct bilirubin 0.3 mg/dL, alkaline
      phosphatase 34 U/L, with INR 0.7. Viral serology for acute hepatitis B, C, E,
      cytomegalovirus, Epstein-Barr virus, and varicella zoster virus was negative. She
      was immune to hepatitis A. Her antinuclear antibody was positive. Her anti-Smith
      antibody, anti-smooth muscle antibody, HFE gene mutation, ceruloplasmin, alpha-1
      antitrypsin serologies were within normal references. An abdomen sonogram showed
      fatty infiltration. Liver biopsy showed moderate to severe portal inflammation
      and marked lobular disarray. Portal and lobular inflammatory infiltrates
      consisted of a mixture of histiocytes, lymphocytes, plasma cells, eosinophils,
      and neutrophils with centrilobular necrosis and focal bridging necrosis, and
      necro-inflammation. After 6 weeks of follow-up, the patient improved physically,
      and the abdomen pain resolved. Ginseng has been widely used in the Chinese
      community as medicinal herb for a variety of conditions for decades. However,
      proper research has never been done regarding its pharmacokinetics, efficacy, and
      safety issues. In our case report, the idiosyncratic DILI resulted from ingestion
      of ginseng as herbal supplementation for premenopausal symptoms. Physicians
      should be aware of and suspect DILI in any patient with acute liver injury, and
      patients should be reminded that all medications and supplements have a potential
      to cause DILI.

PMID- 30186098
TI  - Drug-Induced Autoimmune Hepatitis in a Patient Treated with Minocycline: A Rare
      Adverse Effect.
AB  - Drug-induced autoimmune hepatitis is an acute and potentially severe adverse
      effect, which has been reported following the long-term use of minocycline. The
      condition's typical biochemical findings include an elevated antinuclear antibody
      titer, hypergammaglobulinemia with elevated levels of serum immunoglobulin G,
      and, sometimes, positive anti-smooth muscle antibodies. Characteristically,
      transaminase levels are very elevated, while markers of cholestasis and bilirubin
      levels are mildly increased, and histological features are very similar to those
      observed in sporadic autoimmune hepatitis. Here, we describe an interesting case
      of a young female who developed drug-induced autoimmune hepatitis after taking
      minocycline for the treatment of acne vulgaris.

PMID- 30186099
TI  - Colonic Malakoplakia: A Rare Finding in a Healthy Male.
AB  - Malakoplakia is a rare chronic granulomatous disease that may affect many organs,
      including the lung, brain, adrenal glands, pancreas, bone, and the genitourinary
      tract. The gastrointestinal tract is the most common site of involvement outside
      of the urinary tract. Herein, we present a case of a 65-year-old male who
      presented with abdominal pain and unintentional weight loss. Physical examination
      findings were unremarkable, but colonoscopy revealed an isolated large, flat,
      soft, and pale lesion in the transverse colon. Histopathological examination of
      the lesion showed expansion of the lamina propria due to numerous lymphocytes,
      plasma cells, neutrophils, and polygonal cells. Von Kossa stain showed small
      intracytoplasmic basophilic granular inclusions, and these histiocyte cells
      showed numerous Michaelis-Gutmann bodies, findings considered as diagnostic
      features of colonic malakoplakia. This is a rare case of isolated malakoplakia of
      the transverse colon diagnosed on endoscopic specimens. The majority of reported
      cases have shown an association between systemic diseases and colorectal
      adenocarcinoma. In addition, most reported cases of colonic involvement have been
      in the rectum, sigmoid, and right colon.

PMID- 30186102
TI  - A Cortical Folding Pattern-Guided Model of Intrinsic Functional Brain Networks in
      Emotion Processing.
AB  - There have been increasing studies demonstrating that emotion processing in
      humans is realized by the interaction within or among the large-scale intrinsic
      functional brain networks. Identifying those meaningful intrinsic functional
      networks based on task-based functional magnetic resonance imaging (task fMRI)
      with specific emotional stimuli and responses, and exploring the underlying
      functional working mechanisms of interregional neural communication within the
      intrinsic functional networks are thus of great importance to understand the
      neural basis of emotion processing. In this paper, we propose a novel cortical
      folding pattern-guided model of intrinsic networks in emotion processing: gyri
      serve as global functional connection centers that perform interregional neural
      communication among distinct regions via long distance dense axonal fibers, and
      sulci serve as local functional units that directly communicate with neighboring
      gyri via short distance fibers and indirectly communicate with other distinct
      regions via the neighboring gyri. We test the proposed model by adopting a
      computational framework of dictionary learning and sparse representation of
      emotion task fMRI data of 68 subjects in the publicly released Human Connectome
      Project. The proposed model provides novel insights of functional mechanisms in
      emotion processing.

PMID- 30186100
TI  - Traumatic Stress Produces Distinct Activations of GABAergic and Glutamatergic
      Neurons in Amygdala.
AB  - Posttraumatic stress disorder (PTSD) is an anxiety disorder characterized by
      intrusive recollections of a severe traumatic event and hyperarousal following
      exposure to the event. Human and animal studies have shown that the change of
      amygdala activity after traumatic stress may contribute to occurrences of some
      symptoms or behaviors of the patients or animals with PTSD. However, it is still
      unknown how the neuronal activation of different sub-regions in amygdala changes
      during the development of PTSD. In the present study, we used single prolonged
      stress (SPS) procedure to obtain the animal model of PTSD, and found that 1 day
      after SPS, there were normal anxiety behavior and extinction of fear memory in
      rats which were accompanied by a reduced proportion of activated glutamatergic
      neurons and increased proportion of activated GABAergic neurons in basolateral
      amygdala (BLA). About 10 days after SPS, we observed enhanced anxiety and
      impaired extinction of fear memory with increased activated both glutamatergic
      and GABAergic neurons in BLA and increased activated GABAergic neurons in central
      amygdala (CeA). These results indicate that during early and late phase after
      traumatic stress, distinct patterns of activation of glutamatergic neurons and
      GABAergic neurons are displayed in amygdala, which may be implicated in the
      development of PTSD.

PMID- 30186103
TI  - MRI Asymmetry Index of Hippocampal Subfields Increases Through the Continuum From
      the Mild Cognitive Impairment to the Alzheimer's Disease.
AB  - Objective: It is well-known that the hippocampus presents significant asymmetry
      in Alzheimer's disease (AD) and that difference in volumes between left and right
      exists and varies with disease progression. However, few works investigated
      whether the asymmetry degree of subfields of hippocampus changes through the
      continuum from Mild Cognitive Impairment (MCI) to AD. Thus, aim of the present
      work was to evaluate the Asymmetry Index (AI) of hippocampal substructures as
      possible MRI biomarkers of Dementia. Moreover, we aimed to assess whether the
      subfields presented peculiar differences between left and right hemispheres. We
      also investigated the relationship between the asymmetry magnitude in hippocampal
      subfields and the decline of verbal memory as assessed by Rey's auditory verbal
      learning test (RAVLT). Methods: Four-hundred subjects were selected from ADNI,
      equally divided into healthy controls (HC), AD, stable MCI (sMCI), and
      progressive MCI (pMCI). The structural baseline T1s were processed with
      FreeSurfer 6.0 and volumes of whole hippocampus (WH) and 12 subfields were
      extracted. The AI was calculated as: (|Left-Right|/(Left+Right))*100. ANCOVA was
      used for evaluating AI differences between diagnoses, while paired t-test was
      applied for assessing changes between left and right volumes, separately for each
      group. Partial correlation was performed for exploring relationship between RAVLT
      summary scores (Immediate, Learning, Forgetting, Percent Forgetting) and
      hippocampal substructures AI. The statistical threshold was Bonferroni corrected
      p < 0.05/13 = 0.0038. Results: We found a general trend of increased degree of
      asymmetry with increasing severity of diagnosis. Indeed, AD presented the higher
      magnitude of asymmetry compared with HC, sMCI and pMCI, in the WH (AI mean 5.13
      +/- 4.29 SD) and in each of its twelve subfields. Moreover, we found in AD a
      significant negative correlation (r = -0.33, p = 0.00065) between the AI of
      parasubiculum (mean 12.70 +/- 9.59 SD) and the RAVLT Learning score (mean 1.70 +/
      1.62 SD). Conclusions: Our findings showed that hippocampal subfields AI varies
      differently among the four groups HC, sMCI, pMCI, and AD. Moreover, we found-for
      the first time-that hippocampal substructures had different sub-patterns of
      lateralization compared with the whole hippocampus. Importantly, the severity in
      learning rate was correlated with pathological high degree of asymmetry in
      parasubiculum of AD patients.

PMID- 30186104
TI  - Cross-Modal Stochastic Resonance as a Universal Principle to Enhance Sensory
      Processing.

PMID- 30186101
TI  - The Epigenetic Factor Landscape of Developing Neocortex Is Regulated by
      Transcription Factors Pax6-> Tbr2-> Tbr1.
AB  - Epigenetic factors (EFs) regulate multiple aspects of cerebral cortex
      development, including proliferation, differentiation, laminar fate, and regional
      identity. The same neurodevelopmental processes are also regulated by
      transcription factors (TFs), notably the Pax6-> Tbr2-> Tbr1 cascade expressed
      sequentially in radial glial progenitors (RGPs), intermediate progenitors, and
      postmitotic projection neurons, respectively. Here, we studied the EF landscape
      and its regulation in embryonic mouse neocortex. Microarray and in situ
      hybridization assays revealed that many EF genes are expressed in specific
      cortical cell types, such as intermediate progenitors, or in rostrocaudal
      gradients. Furthermore, many EF genes are directly bound and transcriptionally
      regulated by Pax6, Tbr2, or Tbr1, as determined by chromatin immunoprecipitation
      sequencing and gene expression analysis of TF mutant cortices. Our analysis
      demonstrated that Pax6, Tbr2, and Tbr1 form a direct feedforward genetic cascade,
      with direct feedback repression. Results also revealed that each TF regulates
      multiple EF genes that control DNA methylation, histone marks, chromatin
      remodeling, and non-coding RNA. For example, Tbr1 activates Rybp and Auts2 to
      promote the formation of non-canonical Polycomb repressive complex 1 (PRC1).
      Also, Pax6, Tbr2, and Tbr1 collectively drive massive changes in the subunit
      isoform composition of BAF chromatin remodeling complexes during differentiation:
      for example, a novel switch from Bcl7c (Baf40c) to Bcl7a (Baf40a), the latter
      directly activated by Tbr2. Of 11 subunits predominantly in neuronal BAF, 7 were
      transcriptionally activated by Pax6, Tbr2, or Tbr1. Using EFs, Pax6-> Tbr2-> Tbr1
      effect persistent changes of gene expression in cell lineages, to propagate
      features such as regional and laminar identity from progenitors to neurons.

PMID- 30186105
TI  - Auditory Stream Segregation and Selective Attention for Cochlear Implant
      Listeners: Evidence From Behavioral Measures and Event-Related Potentials.
AB  - The role of the spatial separation between the stimulating electrodes (electrode
      separation) in sequential stream segregation was explored in cochlear implant
      (CI) listeners using a deviant detection task. Twelve CI listeners were
      instructed to attend to a series of target sounds in the presence of interleaved
      distractor sounds. A deviant was randomly introduced in the target stream either
      at the beginning, middle or end of each trial. The listeners were asked to detect
      sequences that contained a deviant and to report its location within the trial.
      The perceptual segregation of the streams should, therefore, improve deviant
      detection performance. The electrode range for the distractor sounds was varied,
      resulting in different amounts of overlap between the target and the distractor
      streams. For the largest electrode separation condition, event-related potentials
      (ERPs) were recorded under active and passive listening conditions. The listeners
      were asked to perform the behavioral task for the active listening condition and
      encouraged to watch a muted movie for the passive listening condition. Deviant
      detection performance improved with increasing electrode separation between the
      streams, suggesting that larger electrode differences facilitate the segregation
      of the streams. Deviant detection performance was best for deviants happening
      late in the sequence, indicating that a segregated percept builds up over time.
      The analysis of the ERP waveforms revealed that auditory selective attention
      modulates the ERP responses in CI listeners. Specifically, the responses to the
      target stream were, overall, larger in the active relative to the passive
      listening condition. Conversely, the ERP responses to the distractor stream were
      not affected by selective attention. However, no significant correlation was
      observed between the behavioral performance and the amount of attentional
      modulation. Overall, the findings from the present study suggest that CI
      listeners can use electrode separation to perceptually group sequential sounds.
      Moreover, selective attention can be deployed on the resulting auditory objects,
      as reflected by the attentional modulation of the ERPs at the group level.

PMID- 30186107
TI  - BrainWave: A Matlab Toolbox for Beamformer Source Analysis of MEG Data.
AB  - BrainWave is an easy-to-use Matlab toolbox for the analysis of
      magnetoencephalography data. It provides a graphical user interface for
      performing minimum-variance beamforming analysis with rapid and interactive
      visualization of evoked and induced brain activity. This article provides an
      overview of the main features of BrainWave with a step-by-step demonstration of
      how to proceed from raw experimental data to group source images and time series
      analyses. This includes data selection and pre-processing, magnetic resonance
      image co-registration and normalization procedures, and the generation of
      volumetric (whole-brain) or cortical surface based source images, and
      corresponding source time series as virtual sensor waveforms and their time
      frequency representations. We illustrate these steps using example data from a
      recently published study on response inhibition (Isabella et al., 2015) using the
      sustained attention to response task paradigm in 12 healthy adult participants.
      In this task participants were required to press a button with their right index
      finger to a rapidly presented series of numerical digits and withhold their
      response to an infrequently presented target digit. This paradigm elicited
      movement-locked brain responses, as well as task-related modulation of brain
      rhythmic activity in different frequency bands (e.g., theta, beta, and gamma),
      and is used to illustrate two different types of source reconstruction
      implemented in the BrainWave toolbox: (1) event-related beamforming of averaged
      brain responses and (2) beamformer analysis of modulation of rhythmic brain
      activity using the synthetic aperture magnetometry algorithm. We also demonstrate
      the ability to generate group contrast images between different response types,
      using the example of frontal theta activation patterns during error responses
      (failure to withhold on target trials). BrainWave is free academic software
      available for download at http://cheynelab.utoronto.ca/brainwave along with
      supporting software and documentation. The development of the BrainWave toolbox
      was supported by grants from the Canadian Institutes of Health Research, the
      National Research and Engineering Research Council of Canada, and the Ontario
      Brain Institute.

PMID- 30186106
TI  - Imaging Protein Misfolding in the Brain Using beta-Sheet Ligands.
AB  - Neurodegenerative diseases characterized by pathological protein accumulation in
      cells are termed "proteinopathies." Although various protein aggregates share
      cross-beta-sheet structures, actual conformations vary among each type of protein
      deposit. Recent progress in the development of radiotracers for positron emission
      tomography (PET) has enabled the visualization of protein aggregates in living
      brains. Amyloid PET tracers have been developed, and are widely used for the
      diagnosis of Alzheimer's disease and non-invasive assessment of amyloid burden in
      clinical trials of anti-dementia drugs. Furthermore, several tau PET tracers have
      been successfully developed and used in the clinical studies. However, recent
      studies have identified the presence of off-target binding of radiotracers in
      areas of tau deposition, suggesting that concomitant neuroinflammatory changes
      might affect tracer binding. In contrast to amyloid and tau PET, there are no
      established tracers for imaging Lewy bodies in the human brain. In this review,
      we describe lessons learned from the development of PET tracers and discuss the
      future direction of tracer development for protein misfolding diseases.

PMID- 30186108
TI  - Generation of iPSC-Derived Human Peripheral Sensory Neurons Releasing Substance P
      Elicited by TRPV1 Agonists.
AB  - Neural crest stem cells (NCPCs) have been shown to differentiate into various
      cell types and tissues during embryonic development, including sensory neurons.
      The few studies addressing the generation of NCPCs and peripheral sensory neurons
      (PSNs) from human induced pluripotent stem cells (hiPSCs), generated sensory
      cells without displaying robust activity. Here, we describe an efficient strategy
      for hiPSCs differentiation into NCPCs and functional PSNs using chemically
      defined media and factors to achieve efficient differentiation, confirmed by the
      expression of specific markers. After 10 days hiPSCs differentiated into NCPCs,
      cells were then maintained in neural induction medium containing defined growth
      factors for PSNs differentiation, followed by 10 days in neonatal human epidermal
      keratinocytes- (HEKn-) conditioned medium (CM). We observed a further increase in
      PSN markers expression and neurites length after CM treatment. The resulting
      neurons elicited action potentials after current injection and released substance
      P (SP) in response to nociceptive agents such as anandamide and resiniferatoxin.
      Anandamide induced substance P release via activation of TRPV1 and not CB1.
      Transcriptomic analysis of the PSNs revealed the main dorsal root ganglia
      neuronal markers and a transcriptional profile compatible with C fiber-low
      threshold mechanoreceptors. TRPV1 was detected by immunofluorescence and RNA-Seq
      in multiple experiments. In conclusion, the developed strategy generated PSNs
      useful for drug screening that could be applied to patient-derived hiPSCs,
      consisting in a powerful tool to model human diseases in vitro.

PMID- 30186109
TI  - Nuclear Respiratory Factor 1 (NRF-1) Controls the Activity Dependent
      Transcription of the GABA-A Receptor Beta 1 Subunit Gene in Neurons.
AB  - While the exact role of beta1 subunit-containing GABA-A receptors (GABARs) in
      brain function is not well understood, altered expression of the beta1 subunit
      gene (GABRB1) is associated with neurological and neuropsychiatric disorders. In
      particular, down-regulation of beta1 subunit levels is observed in brains of
      patients with epilepsy, autism, bipolar disorder and schizophrenia. A
      pathophysiological feature of these disease states is imbalance in energy
      metabolism and mitochondrial dysfunction. The transcription factor, nuclear
      respiratory factor 1 (NRF-1), has been shown to be a key mediator of genes
      involved in oxidative phosphorylation and mitochondrial biogenesis. Using a
      variety of molecular approaches (including mobility shift, promoter/reporter
      assays, and overexpression of dominant negative NRF-1), we now report that NRF-1
      regulates transcription of GABRB1 and that its core promoter contains a conserved
      canonical NRF-1 element responsible for sequence specific binding and
      transcriptional activation. Our identification of GABRB1 as a new target for NRF
      1 in neurons suggests that genes coding for inhibitory neurotransmission may be
      coupled to cellular metabolism. This is especially meaningful as binding of NRF-1
      to its element is sensitive to the kind of epigenetic changes that occur in
      multiple disorders associated with altered brain inhibition.

PMID- 30186110
TI  - M-Calpain Activation Facilitates Seizure Induced KCC2 Down Regulation.
AB  - Potassium chloride co-transporter 2 (KCC2), a major chloride transporter that
      maintains GABAA receptor inhibition in mature mammalian neurons, is down
      regulated in the hippocampus during epileptogenesis. Impaired KCC2 function
      accelerates or facilitates seizure onset. Calpain, with two main subtypes of m-
      and MU-calpain, is a Ca2+-dependent cysteine protease that mediates the
      nonlysosomal degradation of KCC2. Although recent studies have demonstrated that
      calpain inhibitors exert antiepileptic and neuroprotective effects in animal
      models of acute and chronic epilepsy, whether calpain activation affects seizure
      induction through KCC2 degradation remains unknown. Our results showed that: (1)
      Blockade of calpain by non-selective calpain inhibitor MDL-28170 prevented
      convulsant stimulation induced KCC2 downregulation, and reduced the incidence and
      the severity of pentylenetetrazole (PTZ) induced seizures. (2) m-calpain, but not
      MU-calpain, inhibitor mimicked MDL-28170 effect on preventing KCC2
      downregulation. (3) Phosphorylation of m-calpain has been significantly enhanced
      during seizure onset, which was partly mediated by the calcium independent
      MAPK/ERK signaling pathway activation. (4) MAPK/ERK signaling blockade also had
      similar effect as total calpain blockade on both KCC2 downregulation and animal
      seizure induction. The results indicate that upregulated m-calpain activation by
      MAPK/ERK during convulsant stimulation down regulates both cytoplasm- and
      membrane KCC2, and in turn facilitates seizure induction. This finding may
      provide a foundation for the development of highly effective antiepileptic drugs
      targeting of m-calpain.

PMID- 30186113
TI  - Editorial: Structure-Related Intrinsic Electrical States and Firing Patterns of
      Neurons With Active Dendrites.

PMID- 30186112
TI  - Interdependency Between Autophagy and Synaptic Vesicle Trafficking: Implications
      for Dopamine Release.
AB  - Autophagy (ATG) and the Ubiquitin Proteasome (UP) are the main clearing systems
      of eukaryotic cells, in that being ultimately involved in degrading damaged and
      potentially harmful cytoplasmic substrates. Emerging evidence implicates that, in
      addition to their classic catalytic function in the cytosol, autophagy and the
      proteasome act as modulators of neurotransmission, inasmuch as they orchestrate
      degradation and turnover of synaptic vesicles (SVs) and related proteins. These
      findings are now defining a novel synaptic scenario, where clearing systems and
      secretory pathways may be considered as a single system, which senses alterations
      in quality and distribution (in time, amount and place) of both synaptic proteins
      and neurotransmitters. In line with this, in the present manuscript we focus on
      evidence showing that, a dysregulation of secretory and trafficking pathways is
      quite constant in the presence of an impairment of autophagy-lysosomal machinery,
      which eventually precipitates synaptic dysfunction. Such a dual effect appears
      not to be just incidental but it rather represents the natural evolution of
      archaic cell compartments. While discussing these issues, we pose a special
      emphasis on the role of autophagy upon dopamine (DA) neurotransmission, which is
      early affected in several neurological and psychiatric disorders. In detail, we
      discuss how autophagy is engaged not only in removing potentially dangerous
      proteins, which can interfere with the mechanisms of DA release, but also the
      fate of synaptic DA vesicles thus surveilling DA neurotransmission. These
      concepts contribute to shed light on early mechanisms underlying intersection of
      autophagy with DA-related synaptic disorders.

PMID- 30186115
TI  - An Assay for Systematically Quantifying the Vestibulo-Ocular Reflex to Assess
      Vestibular Function in Zebrafish Larvae.
AB  - Zebrafish (Danio rerio) larvae are widely used to study otic functions because
      they possess all five typical vertebrate senses including hearing and balance.
      Powerful genetic tools and the transparent body of the embryo and larva also make
      zebrafish a unique vertebrate model to study otic development. Due to its small
      larval size and moisture requirement during experiments, accurately acquiring the
      vestibulo-ocular reflex (VOR) of zebrafish larva is challenging. In this report,
      a new VOR testing device has been developed for quantifying linear VOR (LVOR) in
      zebrafish larva, evoked by the head motion about the earth horizontal axis. The
      system has a newly designed larva-shaped chamber, by which live fish can be
      steadily held without anesthesia, and the system is more compact and easier to
      use than its predecessors. To demonstrate the efficacy of the system, the LVORs
      in wild-type (WT), dlx3b and dlx4b morphant zebrafish larvae were measured and
      the results showed that LVOR amplitudes were consistent with the morphological
      changes of otoliths induced by morpholino oligonucleotides (MO). Our study
      represents an important advance to obtain VOR and predict the vestibular
      conditions in zebrafish.

PMID- 30186111
TI  - Impaired Glycine Receptor Trafficking in Neurological Diseases.
AB  - Ionotropic glycine receptors (GlyRs) enable fast synaptic neurotransmission in
      the adult spinal cord and brainstem. The inhibitory GlyR is a transmembrane
      glycine-gated chloride channel. The immature GlyR protein undergoes various
      processing steps, e.g., folding, assembly, and maturation while traveling from
      the endoplasmic reticulum to and through the Golgi apparatus, where post
      translational modifications, e.g., glycosylation occur. The mature receptors are
      forward transported via microtubules to the cellular surface and inserted into
      neuronal membranes followed by synaptic clustering. The normal life cycle of a
      receptor protein includes further processes like internalization, recycling, and
      degradation. Defects in GlyR life cycle, e.g., impaired protein maturation and
      degradation have been demonstrated to underlie pathological mechanisms of various
      neurological diseases. The neurological disorder startle disease is caused by
      glycinergic dysfunction mainly due to missense mutations in genes encoding GlyR
      subunits (GLRA1 and GLRB). In vitro studies have shown that most recessive forms
      of startle disease are associated with impaired receptor biogenesis. Another
      neurological disease with a phenotype similar to startle disease is a special
      form of stiff-person syndrome (SPS), which is most probably due to the
      development of GlyR autoantibodies. Binding of GlyR autoantibodies leads to
      enhanced receptor internalization. Here we focus on the normal life cycle of
      GlyRs concentrating on assembly and maturation, receptor trafficking, post
      synaptic integration and clustering, and GlyR
      internalization/recycling/degradation. Furthermore, this review highlights
      findings on impairment of these processes under disease conditions such as
      disturbed neuronal ER-Golgi trafficking as the major pathomechanism for recessive
      forms of human startle disease. In SPS, enhanced receptor internalization upon
      autoantibody binding to the GlyR has been shown to underlie the human pathology.
      In addition, we discuss how the existing mouse models of startle disease
      increased our current knowledge of GlyR trafficking routes and function. This
      review further illuminates receptor trafficking of GlyR variants originally
      identified in startle disease patients and explains changes in the life cycle of
      GlyRs in patients with SPS with respect to structural and functional consequences
      at the receptor level.

PMID- 30186114
TI  - Oxytocin and Vasopressin, and the GABA Developmental Shift During Labor and
      Birth: Friends or Foes?
AB  - Oxytocin (OT) and vasopressin (AVP) are usually associated with sociability and
      reduced stress for the former and antidiuretic agent associated with severe
      stress and pathological conditions for the latter. Both OT and AVP play major
      roles during labor and birth. Recent contradictory studies suggest that they
      might exert different roles on the GABA excitatory/inhibitory developmental
      shift. We reported (Tyzio et al., 2006) that at birth, OT exerts a neuro
      protective action mediated by an abrupt reduction of intracellular chloride
      levels ([Cl-]i) that are high in utero, reinforcing GABAergic inhibition and
      modulating the generation of the first synchronized patterns of cortical
      networks. This reduction of [Cl-]i levels is abolished in rodent models of
      Fragile X Syndrome and Autism Spectrum Disorders, and its restoration attenuates
      the severity of the pathological sequels, stressing the importance of the shift
      at birth (Tyzio et al., 2014). In contrast, Kaila and co-workers (Spoljaric et
      al., 2017) reported excitatory GABA actions before and after birth that are
      modulated by AVP but not by OT, challenging both the developmental shift and the
      roles of OT. Here, I analyze the differences between these studies and suggest
      that the ratio AVP/OT like that of excitatory/inhibitory GABA depend on stress
      and pathological conditions.

PMID- 30186117
TI  - Dichotomous Dopaminergic Control of Ventral Pallidum Neurons.
AB  - The ventral pallidum (VP) is crucially involved in reward processing.
      Dopaminergic afferents reach the VP from the ventral tegmental area (VTA). Recent
      in vivo studies suggest dopamine application increase the firing in the VP.
      However, little is known about the cellular effects of dopamine within the VP. We
      aimed to address this paucity of data using brain slices containing the VP and
      multi-electrode array recordings. Dopamine significantly affected firing in 86%
      of spontaneously active VP neurons. Among the affected neurons, 84% were excited,
      while 16% were inhibited. The selective D1-like receptor agonist SKF81297 also
      had modulatory effects on the majority of VP neurons, but its effects were
      universally excitatory. On the other hand, the D2-like receptor agonist
      quinpirole had modulatory effects on 87% of VP neurons studied. It caused
      significant inhibitory effects in 33% of the cases and excitatory effects in the
      remaining 67%. The effects of D1-like receptor activation were presynaptic as
      blocking synaptic transmission with low Ca2+ abolished the effects of SKF81297
      application. Furthermore, SKF81297 effects were abolished by blocking ionotropic
      glutamate receptors, suggesting that D1-like receptors boost glutamate release,
      which in turn excites VP neurons through postsynaptic glutamate receptors.
      Effects caused by D2-like receptor activation were found to involve pre and
      postsynaptic mechanisms, as low Ca2+ abolished the excitatory effects of
      quinpirole but not the inhibitory ones. Increases in firing frequency (ff) to
      quinpirole application were abolished by a group 2/3 mGluR antagonist, suggesting
      that D2-like receptors cause presynaptic inhibition of glutamate release,
      resulting in reduced postsynaptic activation of inhibitory mGluRs. Conversely,
      the inhibitory effects of quinpirole persisted in low Ca2+ and therefore can be
      attributed to postsynaptic D2-like receptor activation. VP neurons excited by
      dopamine had shorter spike half-widths and are excited by D1-like receptors
      (presynaptically) and by D2-like receptors (postsynaptically). VP neurons
      inhibited by dopamine have longer spike half-widths and while D1-like receptor
      activation has a presynaptic excitatory influence on them, D2-like receptor
      activation has a postsynaptic inhibitory effect that prevails, on balance. These
      data provide novel insights into the cellular mechanisms by which dopamine
      controls information processing within the VP.

PMID- 30186119
TI  - BML-111 Reduces Neuroinflammation and Cognitive Impairment in Mice With Sepsis
      via the SIRT1/NF-kappaB Signaling Pathway.
AB  - Sepsis is a life-threatening state of organ dysfunction caused by infection and
      which can induce severe neurological disorders that lead to neuroinflammation and
      cognitive impairment. Inflammation has been reported to cause neuronal apoptosis
      in sepsis, which can finally lead to cognitive impairment. Previous studies have
      suggested that BML-111 can exhibit anti-inflammatory and proresolution
      activities. Additionally, silent information regulator 1 (SIRT1) can inhibit the
      NF-kappaB signaling pathway in an inflammation state. However, the role of the
      SIRT1/NF-kappaB signaling pathway in the protective effects of BML-111 against
      sepsis-induced neuroinflammation and cognitive impairment remains unclear. This
      study aimed to determine the effects of BML-111 on neuroinflammation and
      cognitive impairment induced by sepsis. Male C57BL/6J mice were subjected to
      cecal ligation and puncture (CLP) or a sham operation. BML-111 was administered
      via intracerebroventricular injection (0.1 mg/kg) immediately after CLP. Boc-2
      (50 MUg/kg) was administered intracerebroventricularly 30 min before CLP, and
      EX527 (10 MUg) was administered every 2 days for a total of three times before
      CLP, also intracerebroventricularly. Some of the surviving mice underwent open
      field, novel-object-recognition, and fear-conditioning behavioral tests at 7 days
      after surgery. Some of the other surviving mice were killed at 24 h after surgery
      to assess synaptic damage (PSD95 and Synapsin1), markers of inflammation [tumor
      necrosis factor alpha (TNF-alpha) and interleukin (IL)-1beta], cytoplasmic p65,
      nuclear p65, Ac- NF-kappaB and SIRT1. At 48 h after CLP, TUNEL and glia
      activation by immunofluorescence investigations were performed on a separate
      cohort of surviving animals. The results suggested that sepsis resulted in
      cognitive impairment, which was accompanied by the decreased the expression of
      PSD95 and Synapsin1, increased amount of TUNEL-positive cells and the activation
      of glias, increased production of TNF-alpha and IL-1beta, increased expression of
      nuclear p65, Ac- NF-kappaB, and decreased expression of SIRT1 and cytoplasmic
      p65. It is especially notable that these abnormalities could be reduced by BML
      111 treatment. EX527, an SIRT1 inhibitor, abolished the effects of BML-111. These
      results demonstrate that BML-111 can reduce the neuroinflammation and cognitive
      impairment induced by sepsis via SIRT/NF-kappaB signaling pathway.

PMID- 30186116
TI  - Importance of GPCR-Mediated Microglial Activation in Alzheimer's Disease.
AB  - Alzheimer's disease (AD) is a progressive neurodegenerative disorder associated
      with impairment of cognition, memory deficits and behavioral abnormalities.
      Accumulation of amyloid beta (Abeta) is a characteristic hallmark of AD.
      Microglia express several GPCRs, which, upon activation by modulators, mediate
      microglial activation and polarization phenotype. This GPCR-mediated microglial
      activation has both protective and detrimental effects. Microglial GPCRs are
      involved in amyloid precursor protein (APP) cleavage and Abeta generation. In
      addition, microglial GPCRs are featured in the regulation of Abeta degradation
      and clearance through microglial phagocytosis and chemotaxis. Moreover, in
      response to Abeta binding on microglial Abeta receptors, they can trigger
      multiple inflammatory pathways. However, there is still a lack of insight into
      the mechanistic link between GPCR-mediated microglial activation and its
      pathological consequences in AD. Currently, the available drugs for the treatment
      of AD are mostly symptomatic and dominated by acetylcholinesterase inhibitors
      (AchEI). The selection of a specific microglial GPCR that is highly expressed in
      the AD brain and capable of modulating AD progression through Abeta generation,
      degradation and clearance will be a potential source of therapeutic intervention.
      Here, we have highlighted the expression and distribution of various GPCRs
      connected to microglial activation in the AD brain and their potential to serve
      as therapeutic targets of AD.

PMID- 30186118
TI  - Important Shapeshifter: Mechanisms Allowing Astrocytes to Respond to the Changing
      Nervous System During Development, Injury and Disease.
AB  - Astrocytes are the most prevalent glial cells in the brain. Historically
      considered as "merely supporting" neurons, recent research has shown that
      astrocytes actively participate in a large variety of central nervous system
      (CNS) functions including synaptogenesis, neuronal transmission and synaptic
      plasticity. During disease and injury, astrocytes efficiently protect neurons by
      various means, notably by sealing them off from neurotoxic factors and repairing
      the blood-brain barrier. Their ramified morphology allows them to perform diverse
      tasks by interacting with synapses, blood vessels and other glial cells. In this
      review article, we provide an overview of how astrocytes acquire their complex
      morphology during development. We then move from the developing to the mature
      brain, and review current research on perisynaptic astrocytic processes, with a
      particular focus on how astrocytes engage synapses and modulate their formation
      and activity. Comprehensive changes have been reported in astrocyte cell shape in
      many CNS pathologies. Factors influencing these morphological changes are
      summarized in the context of brain pathologies, such as traumatic injury and
      degenerative conditions. We provide insight into the molecular, cellular and
      cytoskeletal machinery behind these shape changes which drive the dynamic
      remodeling in astrocyte morphology during injury and the development of
      pathologies.

PMID- 30186121
TI  - Costorage of High Molecular Weight Neurotransmitters in Large Dense Core Vesicles
      of Mammalian Neurons.
AB  - It is today widely accepted that several types of high molecular weight (MW)
      neurotransmitters produced by neurons are synthesized at the cell body,
      selectively stored within large dense core vesicles (LDCVs) and anterogradely
      transported to terminals where they elicit their biological role(s). Among these
      molecules there are neuropeptides and neurotrophic factors, the main focus of
      this perspective article. I here first provide a brief resume of the state of art
      on neuronal secretion, with primary emphasis on the molecular composition and
      mechanism(s) of filling and release of LDCVs. Then, I discuss the perspectives
      and future directions of research in the field as regarding the synthesis and
      storage of multiple high MW transmitters in LDCVs and the possibility that a
      selective sorting of LDCVs occurs along different neuronal processes and/or their
      branches. I also consider the ongoing discussion that diverse types of neurons
      may contain LDCVs with different sets of integral proteins or dial in a different
      fashion with LDCVs containing the same cargo. In addition, I provide original
      data on the size of LDCVs in rat dorsal root ganglion neurons and their central
      terminals in the spinal cord after immunogold labeling for calcitonin gene
      related peptide (CGRP), neuropeptide K, substance P, neurokinin A or
      somatostatin. These data corroborate the idea that, similarly to endocrine cells,
      LDCVs undergo a process of maturation which involves a homotypic fusion followed
      by a reduction in size and condensation of cargo. They also give support to the
      conjecture that release at terminals occurs by cavicapture, a process of partial
      fusion of the vesicle with the axolemma, accompanied by depletion of cargo and
      diminution of size.

PMID- 30186120
TI  - The Endocannabinoid/Cannabinoid Receptor 2 System Protects Against Cisplatin
      Induced Hearing Loss.
AB  - Previous studies have demonstrated the presence of cannabinoid 2 receptor (CB2R)
      in the rat cochlea which was induced by cisplatin. In an organ of Corti-derived
      cell culture model, it was also shown that an agonist of the CB2R protected these
      cells against cisplatin-induced apoptosis. In the current study, we determined
      the distribution of CB2R in the mouse and rat cochleae and examined whether these
      receptors provide protection against cisplatin-induced hearing loss. In a knock
      in mouse model expressing the CB2R tagged with green fluorescent protein, we show
      distribution of CB2R in the organ of Corti, stria vascularis, spiral ligament and
      spiral ganglion cells. A similar distribution of CB2R was observed in the rat
      cochlea using a polyclonal antibody against CB2R. Trans-tympanic administration
      of (2-methyl-1-propyl-1H-indol-3-yl)-1-naphthalenylmethanone (JWH015), a
      selective agonist of the CB2R, protected against cisplatin-induced hearing loss
      which was reversed by blockade of this receptor with 6-iodo-2-methyl-1-[2-(4
      morpholinyl)ethyl]-1H-indol-3-yl](4-methoxyphenyl)methanone (AM630), an
      antagonist of CB2R. JWH015 also reduced the loss of outer hair cells (OHCs) in
      the organ of Corti, loss of inner hair cell (IHC) ribbon synapses and loss of
      Na+/K+-ATPase immunoreactivity in the stria vascularis. Administration of AM630
      alone produced significant hearing loss (measured by auditory brainstem
      responses) which was not associated with loss of OHCs, but led to reductions in
      the levels of IHC ribbon synapses and strial Na+/K+-ATPase immunoreactivity.
      Furthermore, knock-down of CB2R by trans-tympanic administration of siRNA
      sensitized the cochlea to cisplatin-induced hearing loss at the low and middle
      frequencies. Hearing loss induced by cisplatin and AM630 in the rat was
      associated with increased expression of genes for oxidative stress and
      inflammatory proteins in the rat cochlea. In vitro studies indicate that JWH015
      did not alter cisplatin-induced killing of cancer cells suggesting this agent
      could be safely used during cisplatin chemotherapy. These data unmask a
      protective role of the cochlear endocannabinoid/CB2R system which appears
      tonically active under normal conditions to preserve normal hearing. However, an
      exogenous agonist is needed to boost the activity of endocannabinoid/CB2R system
      for protection against a more traumatic cochlear insult, as observed with
      cisplatin administration.

PMID- 30186122
TI  - Intersectional Strategies for Targeting Amacrine and Ganglion Cell Types in the
      Mouse Retina.
AB  - The mammalian retina harbors over 100 different cell types. To understand how
      retinal circuits work, it is essential to systematically access each type. A
      widely used approach for achieving targeted transgene expression exploits
      promoter-driven Cre lines. However, Cre expression in a given transgenic line in
      the retina and elsewhere in the brain is rarely confined to a single cell type,
      contributing ambiguity to the interpretation of results from broadly applied
      manipulations. To obtain unambiguous information about retinal processing, it is
      desirable to have strategies for further restricting transgene expression to a
      few or even to a single cell type. We employed an intersectional strategy based
      on a Cre/Flp double recombinase system to target amacrine and ganglion cell types
      in the inner retina. We analyzed expression patterns in seven Flp drivers and
      then created combinational mouse lines by selective cross breeding with Cre
      drivers. Breeding with Flp drivers can routinely remove labeling from more than
      90% of the cells in Cre drivers, leading to only a handful cell types, typically
      2-3, remaining in the intersection. Cre/Flp combinatorial mouse lines enabled us
      to identify and anatomically characterize retinal cell types with greater ease
      and demonstrated the feasibility of intersectional strategies in retinal
      research. In addition to the retina, we examined Flp expression in the lateral
      geniculate nucleus and superior colliculus. Our results establish a foundation
      for future application of intersectional strategies in the retina and retino
      recipient regions.

PMID- 30186123
TI  - A Developmental Study of Abnormal Behaviors and Altered GABAergic Signaling in
      the VPA-Treated Rat Model of Autism.
AB  - Although studies have investigated the role of gamma-aminobutyric acid
      (GABA)ergic signaling in rodent neural development and behaviors relevant to
      autism, behavioral ontogeny, as underlain by the changes in GABAergic system, is
      poorly characterized in different brain regions. Here, we employed a valproic
      acid (VPA) rat model of autism to investigate the autism-like behaviors and
      GABAergic glutamic acid decarboxylase 67 (GAD67) expression underlying these
      altered behaviors in multiple brain areas at different developmental stages from
      birth to adulthood. We found that VPA-treated rats exhibited behavioral
      abnormalities relevant to autism, including delayed nervous reflex development,
      altered motor coordination, delayed sensory development, autistic-like and
      anxiety behaviors and impaired spatial learning and memory. We also found that
      VPA rats had the decreased expression of GAD67 in the hippocampus (HC) and
      cerebellum from childhood to adulthood, while decreased GAD67 expression of the
      temporal cortex (TC) was only observed in adulthood. Conversely, GAD67 expression
      was increased in the prefrontal cortex (PFC) from adolescence to adulthood. The
      dysregulated GAD67 expression could alter the excitatory-inhibitory balance in
      the cerebral cortex, HC and cerebellum. Our findings indicate an impaired
      GABAergic system could be a major etiological factor occurring in the cerebral
      cortex, HC and cerebellum of human cases of autism, which suggests enhancement of
      GABA signaling would be a promising therapeutic target for its treatment.

PMID- 30186124
TI  - Does Human Experimental Endotoxemia Impact Negative Cognitions Related to the
      Self?
AB  - A role of inflammatory processes in the pathophysiology of depression is
      increasingly recognized. Experimental endotoxemia offers an established model to
      induce transient systemic inflammation in healthy humans, and has been proposed
      as an experimental paradigm of depression. Indeed, different symptoms of
      depression can be observed during experimental endotoxemia, including negative
      mood or dysthymia as key symptoms of depression. Hopelessness and low self-esteem
      constitute common cognitive symptoms in depression, but have not been
      specifically assessed during endotoxemia. Thus, we pooled data from healthy
      volunteers who received low-dose endotoxin (i.e., 0.4 or 0.8 ng/kg
      lipopolysaccharide, LPS) or placebo in three randomized, controlled studies to
      investigate the effects of LPS on cognitive schemata related to depression.
      Validated questionnaires were used to assess self-esteem, hopelessness and the
      vulnerability factor intolerance of uncertainty after intravenous injection of
      LPS or placebo. Plasma tumor necrosis factor (TNF)-alpha and interleukin (IL)-6
      were repeatedly assessed, along with self-reported mood. Because not all
      questionnaires were available from primary studies, data were analyzed in two
      separate data sets: In data set 1, self-esteem and intolerance of uncertainty
      were assessed in N = 87 healthy volunteers, who randomly received either 0.4 or
      0.8 ng/kg LPS or placebo. In data set 2, hopelessness was measured in N = 59
      volunteers who randomly received either LPS (0.8 ng/kg) or placebo. In both data
      sets, LPS-application led to significant increases in TNF-alpha and IL-6,
      reflecting systemic inflammation. Positive mood was significantly decreased in
      response to LPS, in line with inflammation-induced mood impairment. General self
      esteem, intolerance of uncertainty and hopelessness did not differ between LPS-
      and placebo groups, suggesting that these negative cognitive schemata are not
      responsive to acute LPS-induced systemic inflammation. Interestingly, LPS-treated
      volunteers reported significantly lower body-related self-esteem, which was
      associated with increased TNF-alpha concentration. Thus, certain aspects of self
      esteem related to physical attractiveness and sportiness were reduced. It is
      conceivable that this effect is primarily related to physical sickness symptoms
      and reduced physical ability during experimental endotoxemia. With respect to
      cognitive symptoms of depression, it is conceivable that LPS affects cognitive
      processes, but not negative cognitive schemata, which are rather based on
      learning and repeated experiences.

PMID- 30186125
TI  - Alcohol Hangover Increases Conflict Load via Faster Processing of Subliminal
      Information.
AB  - The detrimental effects of acute alcohol intoxication and long-term alcohol
      (ab)use on cognition are well-known. Yet, only little is known about the
      cognitive effects of an acute alcohol hangover, even though it might affect
      executive functions associated with workplace performance or driving skills.
      Given that alcohol hangover may increase the speed of information accumulation,
      we assessed the behavioral effects of conflict load (induced by a subliminal
      prime) on cognitive control, as assessed via the Flanker effect. We employed a
      counter-balanced within-subject design, where n = 25 healthy young males were
      tested once after a sober night and once after a night of experimentally induced
      heavy drinking of cheap brandy/red wine (2.6375 g alcohol per estimated liter of
      body water within 2-3 h). Alcohol hangover neither increased the cognitive
      conflicts induced by consciously processed distractors alone (i.e., the Flanker
      effect), nor modulated conflict adaptation (i.e., the Gratton effect). Instead,
      hangover potentiated the detrimental effects of conflicting subliminal primes on
      top-down cognitive conflicts. This effect was likely due to an increase in the
      speed of information accumulation from visual stimuli and the resulting increase
      in subliminal conflict load induced by incompatible primes. We further found the
      size of this effect to be positively correlated with age and subjective
      sleepiness during the hangover state, but the hangover effect remained
      significant even after correcting for those covariates. We further found no
      correlation of the behavioral effect with the subjective overall rating of
      hangover symptoms or the maximal breath alcohol concentration reached during
      prior intoxication. Taken together, our findings suggest that alcohol hangover
      may affect cognitive performance due to an increase in non-conscious processing
      of visual distractors. While the size of this effect might increase with age and
      sleepiness, it is not entirely dependent on those covariates and not necessarily
      related to subjective ratings of general hangover symptoms/impairment.

PMID- 30186126
TI  - Effect of Modulating Activity of DLPFC and Gender on Search Behavior: A tDCS
      Experiment.
AB  - Studies of search behavior have shown that individuals stop searching earlier and
      accept a lower point than predicted by the optimal, risk-neutral stopping rule.
      This behavior may be related to individual risk preferences. Studies have also
      found correlativity between risk preferences and the dorsolateral prefrontal
      cortex (DLPFC). As risk attitude plays a crucial role in search behavior, we
      studied whether modulating the activity of DLPFC, by using a transcranial direct
      current stimulation (tDCS) device, can change individual search behavior. We
      performed a sequential search task in which subjects decided when to accept a
      point randomly drawn from a uniform distribution. A total of 49 subjects (23
      females, mean age = 21.84 +/- 2.09 years, all right-handed) were recruited at
      Zhejiang University from May 2017 to September 2017. They repeated the task in 80
      trials and received the stimulation at the end of the 40th trial. The results
      showed that after receiving right anodal/left cathodal stimulation, subjects
      increased their searching duration, which led to an increase in their accepted
      point from 778.17 to 826.12. That is, the subjects may have changed their risk
      attitude to search for a higher acceptable point and received a higher benefit.
      In addition, the effect of stimulation on search behavior was mainly driven by
      the female subjects rather than by the male subjects: the female subjects
      significantly increased their accepted point from 764.15 to 809.17 after right
      anodal/left cathodal stimulation, while the male subjects increased their
      accepted point from 794.18 to 845.49, but the change was not significant.

PMID- 30186128
TI  - Perception of Arm Position in Three-Dimensional Space.
AB  - Proprioception refers to the senses of body position, movement, force and effort.
      Previous studies have demonstrated workspace and direction-dependent differences
      in arm proprioceptive sensitivity within the horizontal plane. In addition,
      studies of reaching in the vertical plane have shown that proprioception plays a
      key role in anticipating arm configuration dependent effects of gravity. This
      suggests that proprioceptive sensitivity could vary with the direction of arm
      displacement relative to the gravitational vector, as well as with arm
      configuration. To test these hypotheses, and to characterize proprioception more
      generally, we assessed the direction-dependence and arm postural-dependence of
      proprioceptive sensitivity in 3D space using a novel robotic paradigm. A
      subject's right arm was coupled to a 7-df robot through a trough that stabilized
      the wrist and forearm, allowing for changes in configuration largely at the elbow
      and shoulder. Sensitivity was evaluated using a "same-different" task, where the
      subject's hand was moved 1-4 cm away from an initial "test" position to a 2nd
      "judgment" position. The proportion of trials where subjects responded
      "different" when the positions were different ("hit rate"), and where they
      responded "different" when the positions were the same, ("false alarm rate"),
      were used to calculate d', a measure of sensitivity derived from signal detection
      theory (SDT). Initially, a single initial arm posture was used and displacements
      were performed in six directions: upward, downward, forward, backward, leftward
      and rightward of the test position. In a follow-up experiment, data were obtained
      for four directions and two initial arm postures. As expected, sensitivity (d')
      increased monotonically with distance for all six directions. Sensitivity also
      varied between directions, particularly at position differences of 2 and 3 cm.
      Overall, sensitivity reached near maximal values in this task at 2 cm for the
      leftward/rightward directions, 3 cm for upward/forward and 4 cm for the
      downward/backward directions. In addition, when data were grouped together for
      opposing directions, sensitivity showed a dependence upon arm posture. These data
      suggest arm proprioceptive sensitivity is both anisotropic in 3D space and
      configuration-dependent, which has important implications for sensorimotor
      control of the arm and human-robot interactions.

PMID- 30186127
TI  - Biological and Psychological Perspectives of Resilience: Is It Possible to
      Improve Stress Resistance?
AB  - The term "resilience" refers to the ability to adapt successfully to stress,
      trauma and adversity, enabling individuals to avoid stress-induced mental
      disorders such as depression, posttraumatic stress disorder (PTSD) and anxiety.
      Here, we review evidence from both animal models and humans that is increasingly
      revealing the neurophysiological and neuropsychological mechanisms that underlie
      stress susceptibility, as well as active mechanisms underlying the resilience
      phenotype. Ultimately, this growing understanding of the neurobiological
      mechanisms of resilience should result in the development of novel interventions
      that specifically target neural circuitry and brain areas that enhance resilience
      and lead to more effective treatments for stress-induced disorders. Stress
      resilience can be improved, but the outcomes and effects depend on the type of
      intervention and the species treated.

PMID- 30186131
TI  - Intra- and Inter-Scanner Reliability of Voxel-Wise Whole-Brain Analytic Metrics
      for Resting State fMRI.
AB  - As the multi-center studies with resting-state functional magnetic resonance
      imaging (RS-fMRI) have been more and more applied to neuropsychiatric studies,
      both intra- and inter-scanner reliability of RS-fMRI are becoming increasingly
      important. The amplitude of low frequency fluctuation (ALFF), regional
      homogeneity (ReHo), and degree centrality (DC) are 3 main RS-fMRI metrics in a
      way of voxel-wise whole-brain (VWWB) analysis. Although the intra-scanner
      reliability (i.e., test-retest reliability) of these metrics has been widely
      investigated, few studies has investigated their inter-scanner reliability. In
      the current study, 21 healthy young subjects were enrolled and scanned with blood
      oxygenation level dependent (BOLD) RS-fMRI in 3 visits (V1 - V3), with V1 and V2
      scanned on a GE MR750 scanner and V3 on a Siemens Prisma. RS-fMRI data were
      collected under two conditions, eyes open (EO) and eyes closed (EC), each lasting
      8 minutes. We firstly evaluated the intra- and inter-scanner reliability of ALFF,
      ReHo, and DC. Secondly, we measured systematic difference between two scanning
      visits of the same scanner as well as between two scanners. Thirdly, to account
      for the potential difference of intra- and inter-scanner local magnetic field
      inhomogeneity, we measured the difference of relative BOLD signal intensity to
      the mean BOLD signal intensity of the whole brain between each pair of visits.
      Last, we used percent amplitude of fluctuation (PerAF) to correct the difference
      induced by relative BOLD signal intensity. The inter-scanner reliability was much
      worse than intra-scanner reliability; Among the VWWB metrics, DC showed the worst
      (both for intra-scanner and inter-scanner comparisons). PerAF showed similar
      intra-scanner reliability with ALFF and the best reliability among all the 4
      metrics. PerAF reduced the influence of BOLD signal intensity and hence increase
      the inter-scanner reliability of ALFF. For multi-center studies, inter-scanner
      reliability should be taken into account.

PMID- 30186130
TI  - Alterations of Muscle Synergies During Voluntary Arm Reaching Movement in
      Subacute Stroke Survivors at Different Levels of Impairment.
AB  - Motor system uses muscle synergies as a modular organization to simplify the
      control of movements. Motor cortical impairments, such as stroke and spinal cord
      injuries, disrupt the orchestration of the muscle synergies and result in
      abnormal movements. In this paper, the alterations of muscle synergies in
      subacute stroke survivors were examined during the voluntary reaching movement.
      We collected electromyographic (EMG) data from 35 stroke survivors, ranging from
      Brunnstrom Stage III to VI, and 25 age-matched control subjects. Muscle synergies
      were extracted from the activity of 7 upper-limb muscles via nonnegative matrix
      factorization under the criterion of 95% variance accounted for. By comparing the
      structure of muscle synergies and the similarity of activation coefficients
      across groups, we can validate the increasing activation of pectoralis major
      muscle and the decreasing activation of elbow extensor of triceps in stroke
      groups. Furthermore, the similarity of muscle synergies was significantly
      correlated with the Brunnstrom Stage (R = 0.52, p < 0.01). The synergies of
      stroke survivors at Brunnstrom Stage IV-III gradually diverged from those of
      control group, but the activation coefficients remained the same after stroke,
      irrespective of the recovery level.

PMID- 30186132
TI  - Psoriasis Vulgaris Exacerbation during Treatment with a PD-1 Checkpoint
      Inhibitor: Case Report and Literature Review.
AB  - Objective: The incidence of immune-related adverse events is growing as the use
      of checkpoint inhibitors is exponentially increasing. Cutaneous adverse events
      are among the most frequent immune-related adverse events. The purpose of this
      case report and literature review is to highlight psoriasis as a potential
      adverse event with need for early recognition. Case Report and Literature Review:
      We describe the case of a 65-year-old woman with psoriasis exacerbation while
      treated with nivolumab (anti-PD-1) for a stage IV melanoma. She had a history of
      scalp psoriasis but she presented with psoriatic lesions on both lower and upper
      limbs. Our patient was treated with topical steroids. So far, 34 other cases with
      an exacerbation of psoriasis during treatment with anti-PDL-1 or PD-1 therapy
      have been reported in the literature. A broad range of therapies are described,
      without any available guidelines for this particular condition. Conclusion:
      Psoriasis exacerbation is an established side effect of PD-1/PDL-1 checkpoint
      inhibitors with 35 reported cases. Early recognition and management are
      challenging as there are no clear guidelines available. A close collaboration
      between oncologist and dermatologist is mandatory to manage this immune-related
      adverse event.

PMID- 30186133
TI  - Atezolizumab-Induced Stevens-Johnson Syndrome in a Patient with Non-Small Cell
      Lung Carcinoma.
AB  - Atezolizumab is a humanized anti-PD-L1 immune checkpoint antibody that is
      currently used in many kinds of advanced carcinoma including metastatic non-small
      cell lung cancer. The cutaneous side effect profile reported only 20$ of the
      patients which had only mild maculopapular rash that required no treatment. There
      is no case report of anti-PD-L1 antibody-induced Stevens-Johnson syndrome
      (SJS)/toxic epidermal necrolysis (TEN) eruptions. To the best of our knowledge,
      there is no case report of atezolizumab-induced SJS or SJS/TEN induced by anti-PD
      L1 immune checkpoint antibodies. We believe that our report will be useful to
      dermatologists who are consultants in the inpatient settings, as atezolizumab is
      an anti-neoplastic agent that has a potential to be used in multiple
      malignancies.

PMID- 30186134
TI  - Neurosarcoidosis following Immune Checkpoint Inhibition.
AB  - Recently, immune checkpoint inhibitors have revolutionized cancer care by
      enhancing anti-tumor immunity. However, by virtue of stimulating the immune
      system, they can lead to immune-related adverse events (irAEs). Neurologic irAEs
      are uncommon but are becoming increasingly recognized and can be quite serious or
      even fatal. Furthermore, central nervous system (CNS) manifestations may be
      difficult to distinguish from CNS metastases, posing management challenges. Here,
      we describe a patient who developed exacerbation of sarcoidosis leading to CNS
      involvement following dual checkpoint blockade with nivolumab and ipilimumab for
      metastatic melanoma and review the relevant literature.

PMID- 30186135
TI  - Ado-Trastuzumab Emtansine-Induced Pulmonary Toxicity: A Single-Institution
      Retrospective Review.
AB  - Purpose: T-DM1 is an antibody drug conjugate with proven efficacy in metastatic
      breast cancer for progressive disease refractory to trastuzumab. Drug-induced
      pneumonitis is a rare serious potential adverse effect. The purpose of this
      review was to estimate the incidence of pulmonary toxicity at our institution.
      Methods: A retrospective analysis of electronic medical record data inclusive of
      all women and men aged 18 years and older treated with T-DM1 at out institution
      was undertaken. The records were reviewed for clinical symptoms and/or
      radiographic evidence concerning for pneumonitis. We identified variables of
      interest with regard to potential risk factors for toxicity. Results: A total of
      50 patients were included, 6 (12$) of whom had radiographic and/or clinical
      symptoms concerning for T-DM1-induced pneumonitis. All 6 patients had metastatic
      or unresectable breast cancer. Of the 6 patients, 5 (83$) had suspected pulmonary
      metastases, 1 (17$) had a history of underlying lung disease, and 5 (83$) had a
      history of prior taxane therapy. Pulmonary metastases (p = 0.38), the median
      number of treatment cycles (p = 0.29), prior taxane therapy (p = 0.99),
      underlying lung disease (p = 0.99), and hormone receptor positivity (p = 0.66)
      did not have any statistical significance for an association with pneumonitis.
      Conclusion: Pneumonitis is a recognized toxic effect of T-DM1. While our sample
      size was small, the number of events was higher than described in the literature,
      which may be an artifact of referral bias. Future studies with a larger sample
      population may detect potential risk factors for toxicity.

PMID- 30186129
TI  - Amygdala Represents Diverse Forms of Intangible Knowledge, That Illuminate Social
      Processing and Major Clinical Disorders.
AB  - Amygdala is an intensively researched brain structure involved in social
      processing and multiple major clinical disorders, but its functions are not well
      understood. The functions of a brain structure are best hypothesized on the basis
      of neuroanatomical connectivity findings, and of behavioral, neuroimaging,
      neuropsychological and physiological findings. Among the heaviest neuroanatomical
      interconnections of amygdala are those with perirhinal cortex (PRC), but these
      are little considered in the theoretical literature. PRC integrates complex,
      multimodal, meaningful and fine-grained distributed representations of objects
      and conspecifics. Consistent with this connectivity, amygdala is hypothesized to
      contribute meaningful and fine-grained representations of intangible knowledge
      for integration by PRC. Behavioral, neuroimaging, neuropsychological and
      physiological findings further support amygdala mediation of a diversity of such
      representations. These representations include subjective valence, impact,
      economic value, noxiousness, importance, ingroup membership, social status,
      popularity, trustworthiness and moral features. Further, the formation of
      amygdala representations is little understood, and is proposed to be often
      implemented through embodied cognition mechanisms. The hypothesis builds on
      earlier work, and makes multiple novel contributions to the literature. It
      highlights intangible knowledge, which is an influential but insufficiently
      researched factor in social and other behaviors. It contributes to understanding
      the heavy but neglected amygdala-PRC interconnections, and the diversity of
      amygdala-mediated intangible knowledge representations. Amygdala is a social
      brain region, but it does not represent species-typical social behaviors. A novel
      proposal to clarify its role is postulated. The hypothesis is also suggested to
      illuminate amygdala's involvement in several core symptoms of autism spectrum
      disorder (ASD). Specifically, novel and testable explanations are proposed for
      the ASD symptoms of disorganized visual scanpaths, apparent social disinterest,
      preference for concrete cognition, aspects of the disorder's heterogeneity, and
      impairment in some activities of daily living. Together, the presented hypothesis
      demonstrates substantial explanatory potential in the neuroscience, social and
      clinical domains.

PMID- 30186136
TI  - A Case of Vanishing Metastatic Mass: Right Atrial Mass in the Setting of Primary
      Epithelioid Hemangioendothelioma of the Spine.
AB  - Epithelioid hemangioendothelioma (EHE) is a rare low-grade vascular neoplasm that
      is characterized as intermediate between benign hemangioma and high-grade
      angiosarcoma affecting 1 in 1,000,000 people worldwide. It has been described
      throughout the body with lung, liver, skin, and bone being the most frequent
      sites. Primary EHE of the spine has been reported in 56 cases so far with no
      correlation of age and sex. Our case highlights a rare clinical presentation,
      etiopathogenesis, diagnosis, and treatment of EHE of the spine with metastasis to
      the right atrium. This is the first documented case of EHE of the spine with
      metastatic spread to the heart treated with bevacizumab leading to resolution of
      the heart metastatic mass. Further studies are warranted to develop a treatment
      formula for this rare tumor, to consider combination chemotherapy and new
      adjuvant targeted immunotherapies to prevent progression of disease.

PMID- 30186137
TI  - Searching for the Culprit: Metastases from a Cancer of Unknown Primary.
AB  - We report a case of metastases from a cancer of unknown primary whose primary
      site could not be identified during the appropriate pretreatment evaluation. The
      patient was a 58-year-old woman with a history of passive smoking and with no
      history of cancer in the family. Her current condition started with asthenia,
      adynamia, and pallor, followed by palpitations. An abdominopelvic computed
      tomography (CT) scan was performed, showing multiple osteolytic lesions
      distributed in all bone structures and axillary adenopathy on the left side. As
      part of the approach and given the high suspicion of multiple myeloma, tests were
      performed. The results were negative for multiple myeloma. A PET-CT scan was
      performed and showed left axillary adenopathy. The breasts and other organs were
      not affected. Left axillary lymph node resection revealed breast primary
      metastatic pleomorphic lobular carcinoma. Due to the metastatic disease (caused
      by the primary breast cancer), it was decided to start chemotherapy.

PMID- 30186138
TI  - Severe Gastritis after Administration of Nivolumab and Ipilimumab.
AB  - Immune checkpoint inhibitors such as ipilimumab, a cytotoxic T-lymphocyte
      associated antigen-4 inhibitor, have been widely used for advanced malignancies.
      As these inhibitors improve antitumor immunity via T-cell modulation, immune
      mediated adverse events associated with T-cell activation, such as colitis, might
      occur. Herein, we describe a 75-year-old Japanese woman with metastatic malignant
      melanoma who developed hemorrhagic gastritis after ipilimumab treatment. There
      was no macroscopic or clinical improvement of gastritis after proton pump
      inhibitor treatment. However, her condition improved after approximately 3 weeks
      of corticosteroid therapy and Helicobacter pylori eradication. This case suggests
      a potential association between severe gastritis and immune checkpoint inhibitor
      treatment. Although several reports have mentioned ipilimumab-associated colitis,
      gastritis is considered to be rare. In the present case, H. pylori-associated
      gastritis might have been exacerbated by the T-cell modulation effect of
      ipilimumab. To date, no report has clarified the mechanism by which ipilimumab
      modifies H. pylori infection. The present treatment course provides a helpful
      perspective for similar cases.

PMID- 30186139
TI  - Aromatase Inhibitor-Associated Tendinopathy and Muscle Tendon Rupture: Report of
      Three Cases of This Exceedingly Rare Adverse Event.
AB  - Aromatase inhibitors (AIs) are a commonly used antihormonal therapy in the
      treatment of breast cancer in postmenopausal women, specifically in the treatment
      of hormone receptor-positive breast cancer. AI-associated tendinopathy and muscle
      tendon rupture is exceedingly rare. Until now, only one case with AI-associated
      severe tendinopathy has been reported in the medical literature, and there are no
      recorded cases of AI-associated muscle tendon rapture. We report three cases of
      postmenopausal women with hormone receptor-positive breast cancer, who
      experienced tendinopathy or muscle tendon rupture under antihormonal treatment
      with letrozole. All of the three women were in the adjuvant setting, and the
      treatment of tendinopathy or tendon rupture consisted of AI discontinuation,
      initiation of corticosteroids, or surgical treatment. Diagnosis was made via MRI.
      Furthermore, in our cases, there were no signs of underlying systemic disease,
      there was no abnormal physical activity preceding the complaints, and there was
      no use of other drugs beside letrozole. AIs are one of the most commonly used
      drugs in antihormonal therapy for hormone receptor-positive breast cancer. In
      every case of a female patient with hormone receptor-positive breast cancer under
      treatment with AIs and arthralgia, an MRI should be performed in order to exclude
      the presence of tendinopathy or muscle tendon rupture.

PMID- 30186140
TI  - Sarcoid-Like Granulomatosis Induced by Nivolumab Treatment in a Lung Cancer
      Patient.
AB  - Nivolumab, an anti-PD-1 antibody, inhibits binding between PD-1 and PD-1 ligand
      and activates antigen-specific T cells that have become unresponsive to cancer
      cells. Although it is recommended as a second-line therapy in gene mutation
      negative non-small-cell lung cancer, interstitial pneumonia is a well-known side
      effect of the drug; however, granulomatous lesions have rarely been reported. We
      describe the case of an 81-year-old male with cT1aN2M1b stage IV pleomorphic
      carcinoma of the left upper lobe of the lung. After primary treatment with
      carboplatin and paclitaxel, recurrence was observed in the left supraclavicular
      lymph node and left adrenal gland. We initiated the administration of nivolumab
      as a secondary treatment. Reduction was observed in the swelling of the left
      supraclavicular lymph node and left adrenal gland, but the tumor shadow in the
      right upper lobe appeared to increase. Bronchoscopy was performed, and the biopsy
      result showed granulomas; the findings resembled a sarcoid-like granulomatous
      reaction. The shadows eventually disappeared with nivolumab discontinuation;
      thus, we concluded that the sarcoid-like granulomatous reaction had resulted from
      nivolumab administration. Based on our observations, we suggest that when
      invasive shadows are observed after nivolumab administration, it is necessary to
      differentiate between disease progression and interstitial pneumonia. Moreover,
      the decision to reinitiate nivolumab treatment requires careful judgment in
      future instances of cancer recurrence.

PMID- 30186141
TI  - Leukoerythroblastosis with Cytopenia as an Initial Presentation of Lung
      Adenocarcinoma.
AB  - A 74-year-old male with a history of chronic lymphocytic leukemia (CLL)
      previously treated with fludarabine/cyclophosphamide/rituximab (FCR) 5 years ago,
      presented with progressive fatigue, mucocutaneous bleeding, and cytopenias
      (hemoglobin 51 g/L, platelets 8.0 * 109/L, lymphocytes 0.4 * 109/L). He had
      normal respiratory findings, and no lymphadenopathy or hepatosplenomegaly.
      Further workup revealed a small spiculated lung nodule and multiple sclerotic
      bony lesions. Due to bleeding/profound thrombocytopenia, lung biopsy was not
      feasible. Peripheral smear revealed leukoerythroblastosis with few nucleated red
      blood cells and left shift of granulocytes. Bone marrow (BM) aspirate yielded a
      dry tap with clusters of extrinsic atypical cells on touch preparations. BM core
      biopsy showed infiltration and near complete replacement by a population of
      highly atypical cells with surrounding fibrosis. Cells were positive for
      cytokeratins CK7 and CK8/18, Napsin A, and thyroid transcription factor-1,
      specific for a primary poorly differentiated lung adenocarcinoma.
      Leukoerythroblastosis in association with cytopenia often indicates a BM
      infiltration and warrants an early BM biopsy to rule out hematological and solid
      malignancies, particularly in CLL patients treated with FCR. In our case, a
      diagnosis of a lung adenocarcinoma was established by BM examination, the only
      clinically feasible diagnostic modality.

PMID- 30186142
TI  - Acute Myeloid Leukemia with Myelodysplasia-Related Changes in a Patient with
      Crohn's Disease Treated with Immunosuppressive Therapy.
AB  - We report a case of acute myeloid leukemia with myelodysplasia-related changes in
      a patient with Crohn's disease. The patient was diagnosed with Crohn's disease at
      the age of 47 years and was treated with the tumor necrosis factor alpha
      inhibitors adalimumab and infliximab, and a short course of azathioprine. Four
      years later, the patient developed acute myeloid leukemia with myelodysplasia
      that involved mainly erythropoiesis. Crohn's disease is associated with an
      increased risk of cancers including hematological malignancies. Cancer
      surveillance including hematology assessment is warranted to monitor the patients
      on immunosuppressive therapy.

PMID- 30186143
TI  - Accurate Detection of Tumor Infiltration by 11C-Methionine Positron Emission
      Tomography in a Patient with Central Nervous System Intravascular Lymphoma: A
      Case Report.
AB  - Intravascular lymphoma (IVL) is a rare and clinically devastating subtype of
      extranodal diffuse large B-cell lymphoma with a distinct presentation. Diagnostic
      difficulty derives from marked variability in clinical presentations and
      nonspecific laboratory and radiological findings, especially when central nervous
      system (CNS) symptoms are the only manifestation. Establishing the diagnosis
      premortem thus remains a major challenge. We describe a 70-year-old male with CNS
      IVL. He presented with acute onset of neurocognitive impairments. Diffusion
      weighted magnetic resonance imaging (MRI) showed multiple high-intensity areas
      suggesting occlusive cerebrovascular disease due to emboli, but extensive
      investigations detected no embolic sources. Intracranial neoplasm was included in
      a differential diagnosis based on elevated serum lactate dehydrogenase and
      interleukin 2 receptor levels. Gadolinium-enhanced MRI or 18-fluorodeoxyglucose
      positron emission tomography (PET) failed to demonstrate specific findings
      leading to a definite diagnosis, while 11C-methionine PET (MET-PET) distinctively
      demonstrated an area of focally increased MET uptake in the frontal cortex,
      suggesting the extent of tumor infiltration. Stereotactic biopsy was conducted
      under MET-PET imaging guidance and immunohistological examinations confirmed the
      proliferation and aggregation of CD20-positive lymphoma cells within the lumina
      of small blood vessels. The findings of the present case first suggest that MET
      PET may provide important information on the diagnosis of CNS IVL and on the
      selection of the optimal site for brain biopsy. Further investigation is
      necessary to clarify whether positive findings on MET-PET are truly specific and
      pathognomonic for CNS IVL.

PMID- 30186144
TI  - Toxic Epidermal Necrolysis in a Patient with Autoimmune Limbic Encephalitis with
      Anti-Glutamate Receptor Antibodies.
AB  - We report on a 44-year-old woman who was diagnosed with toxic epidermal
      necrolysis (TEN) during the recovery phase from autoimmune limbic encephalitis
      with anti-glutamate receptor antibodies. Both, autoimmune limbic encephalitis and
      TEN are very rare diseases. The co-existence of the two diseases has not yet been
      reported. We speculate that the total of 18 drugs needed for the treatment of
      encephalitis might have increased the risk of TEN. Similar reports would be
      required to elucidate the pathophysiology of the co-existence.

PMID- 30186145
TI  - Ultrabiomicroscopy Anterior Segment Evaluation of Ocular Contusive Trauma Caused
      by Pressurized Bottled Drink Caps: A Case Report.
AB  - We report the case of a patient presented to the emergency department because of
      a contusive trauma from a pressurized bottled drink cap. During the visit, the
      patient indicated that he had been hit in his left eye by a cork while he was
      opening a sparkling wine bottle. He underwent a total ophthalmology examination.
      He had an important reduction of visual acuity, corneal swelling, Descemet's
      folds, and hyphema. Therefore, we decided to perform ultrabiomicroscopy (UBM) of
      the anterior segment to study the endothelial damage and Descemet's membrane. UBM
      images confirmed the direct biomicroscopy, highlighting the damaged location.

PMID- 30186146
TI  - Unilateral Multifocal Intraocular Lens Implantation in a Patient with Adie's
      Pupil.
AB  - Purpose: To report a case of a patient with unilateral Adie's pupil who underwent
      bilateral cataract extraction with multifocal and monofocal posterior chamber
      intraocular lens (IOL) implantation. Methods: A 74-year-old woman presented to
      our institution complaining of worsening near vision. Gross examination revealed
      a 6-mm fixed pupil on the right eye (OD) and a 5-mm pupil reacting to 3 mm with
      light on the left eye (OS). Slit lamp examination revealed a tonic pupil with an
      exaggerated pupillary constriction to dilute pilocarpine OD. Dilated exam
      revealed 2-3+ nuclear and cortical lens changes bilaterally. The patient's active
      lifestyle, personality, and biometry measurements made her a good candidate for
      multifocal IOL (MfIOL) implantation OS. Femtosecond laser-assisted cataract
      extraction with a ReSTOR +3 ADD (SN60D1) implantation was performed OS. Monofocal
      lens implantation (SN60WF) was performed OD 6 months later. Results: One year
      postoperatively, our patient had an uncorrected visual acuity (VAsc) of 20/15 for
      distance and J10 for near OD. Her VAsc was 20/25 +1 for distance and J1 for near
      OS. Visual acuity when using both eyes was 20/15 for distance and J1 for near.
      Conclusion: Optimizing success for MfIOL implantation is a multifactorial
      process. Large pupils preoperatively are of particular concern, as this may lead
      to increased dysphotopsia with pupil-dependent MfIOLs. Thus, patients with
      unilateral mydriasis, such as Aide's pupil, may have a beneficial outcome
      combining multifocal-monofocal implantation after bilateral cataract extraction,
      especially if they are not a candidate for monovision but desire spectacle
      independence.

PMID- 30186147
TI  - A 12-Year-Old Girl with Bilateral Coats Disease and ABCA4 Gene Mutation.
AB  - A 12-year-old girl with bilateral stage 2B Coats disease was screened
      meticulously for a possible underlying systemic disease as she was female and the
      disease was bilateral. Full systemic workout turned out to be unremarkable.
      However, an ABCA4 gene mutation was found in the genetic analysis. NDP and TINF2
      gene mutations were not present. She was successfully treated with a bilateral,
      single intravitreal injection of dexamethasone implant and a single session of
      indirect laser photocoagulation with a relatively good anatomic and functional
      result. To the best of our knowledge, the present case is the only reported case
      of Coats disease with an ABCA4 gene mutation.

PMID- 30186148
TI  - An Unusual Case of DMEK Graft Loss into the Vitreous and Its Successful Retrieval
      and Survival.
AB  - Purpose: The aim of this article is to report an unusual case of postoperative
      graft loss into the vitreous cavity after Descemet membrane endothelial
      keratoplasty (DMEK) in a patient with an unstable iris-lens diaphragm (scleral
      fixated intraocular lens [sf-IOL]) and its successful retrieval with a favourable
      outcome. Methods: This is a retrospective case report. Results: DMEK procedure
      was performed in a vitrectomized eye of an 80-year-old woman with pre-existing sf
      IOL due to pseudophakic bullous keratopathy. In the setting of an inadvertently
      created oversized Ando iridectomy and unstable iris-lens diaphragm due to sf-IOL,
      repeated loss of an anterior chamber gas tamponade occurred. At the 3rd
      postoperative day, the patient noticed a change in visual perception, and we
      could detect a loss of the graft into the vitreous via B-scan ultrasound. A 23-G
      vitrectomy was performed promptly to recover the graft using a bimanual hand-over
      hand technique. Six months after DMEK, the patient had a clear cornea without
      dehiscences with a central corneal thickness of 533 um and endothelial cell count
      of 1,219 cells/mm2. Conclusions: This case demonstrates the possibility of graft
      recovery from the vitreous after DMEK and subsequent corneal clearing despite
      unstable iris-lens diaphragm and vitrectomized eye.

PMID- 30186149
TI  - Blood-Cerebrospinal Fluid Barrier Gradients in Mild Cognitive Impairment and
      Alzheimer's Disease: Relationship to Inflammatory Cytokines and Chemokines.
AB  - Background: The pathophysiology underlying altered blood-cerebrospinal fluid
      barrier (BCSFB) function in Alzheimer's disease (AD) is unknown but may relate to
      endothelial cell activation and cytokine mediated inflammation. Methods:
      Cerebrospinal fluid (CSF) and peripheral blood were concurrently collected from
      cognitively healthy controls (N = 21) and patients with mild cognitive impairment
      (MCI) (N = 8) or AD (N = 11). The paired serum and CSF samples were assayed for a
      panel of cytokines, chemokines, and related trophic factors using multiplex
      ELISAs. Dominance analysis models were conducted to determine the relative
      importance of the inflammatory factors in relationship to BCSFB permeability, as
      measured by CSF/serum ratios for urea, creatinine, and albumin. Results: BCSFB
      disruption to urea, a small molecule distributed by passive diffusion, had a full
      model coefficient of determination (r2) = 0.35, and large standardized dominance
      weights (>0.1) for monocyte chemoattractant protein-1, interleukin (IL)-15, IL
      1ralpha, and IL-2 in serum. BCSFB disruption to creatinine, a larger molecule
      governed by active transport, had a full model r2 = 0.78, and large standardized
      dominance weights for monocyte inhibitor protein-1b in CSF and tumor necrosis
      factor-alpha in serum. BCSFB disruption to albumin, a much larger molecule, had a
      full model r2 = 0.62, and large standardized dominance weights for IL-17a,
      interferon-gamma, IL-2, and VEGF in CSF, as well IL-4 in serum. Conclusions:
      Inflammatory proteins have been widely documented in the AD brain. The results of
      the current study suggest that changes in BCSFB function resulting in altered
      permeability and transport are related to expression of specific inflammatory
      proteins, and that the shifting distribution of these proteins from serum to CSF
      in AD and MCI is correlated with more severe perturbations in BCSFB function.

PMID- 30186150
TI  - Both Basal and Acute Restraint Stress-Induced c-Fos Expression Is Influenced by
      Age in the Extended Amygdala and Brainstem Stress Centers in Male Rats.
AB  - The hypothalamus-pituitary-adrenal axis (HPA) is the main regulator of the stress
      response. The key of the HPA is the parvocellular paraventricular nucleus of the
      hypothalamus (pPVN) controlled by higher-order limbic stress centers. The
      reactivity of the HPA axis is considered to be a function of age, but to date,
      little is known about the background of this age-dependency. Sporadic literature
      data suggest that the stress sensitivity as assessed by semi-quantitation of the
      neuronal activity marker c-Fos may also be influenced by age. Here, we aimed at
      investigating the HPA activity and c-Fos immunoreactivity 2 h after the beginning
      of a single 60 min acute restraint stress in eight age groups of male Wistar
      rats. We hypothesized that the function of the HPA axis (i.e., pPVN c-Fos and
      blood corticosterone (CORT) level), the neuronal activity of nine stress-related
      limbic areas (i.e., magnocellular PVN (mPVN), medial (MeA), central (CeA),
      basolateral nuclei of the amygdala, the oval (ovBNST), dorsolateral (dlBNST),
      dorsomedial (dmBNST), ventral and fusiform (fuBNST) divisions of the bed nucleus
      of the stria terminalis (BNST)), and two brainstem stress centers such as the
      centrally projecting Edinger-Westphal nucleus (cpEW) and dorsal raphe nucleus
      (DR) show age dependency in their c-Fos response. The somatosensory barrel cortex
      area (S1) was evaluated to test whether the age dependency is specific for stress
      centers. Our results indicate that the stress-induced rise in blood CORT titer
      was lower in young age reflecting relatively low HPA activity. All 12 stress
      related brain areas showed c-Fos response that peaked at 2 months of age. The
      magnitude of c-Fos immunoreactivity correlated negatively with age in seven
      regions (MeA, CeA, ovBNST, dlBNST, dmBNST, fuBNST and pPVN). Unexpectedly, the
      CeA, ovBNST and cpEW showed a considerable basal c-Fos expression in 1-month-old
      rats which decreased with age. The S1 showed a U-shaped age-related dynamics in
      contrast to the decline observed in stress centers. We conclude that the age- and
      brain area dependent dynamics in stress-induced neuronal activity pattern may
      contribute to the age dependance of the stress reactivity. Further studies are in
      progress to determine the neurochemical identity of neurons showing age-dependent
      basal and/or stress-induced c-Fos expression.

PMID- 30186151
TI  - Biological Brain Age Prediction Using Cortical Thickness Data: A Large Scale
      Cohort Study.
AB  - Brain age estimation from anatomical features has been attracting more attention
      in recent years. This interest in brain age estimation is motivated by the
      importance of biological age prediction in health informatics, with an
      application to early prediction of neurocognitive disorders. It is well-known
      that normal brain aging follows a specific pattern, which enables researchers and
      practitioners to predict the age of a human's brain from its degeneration. In
      this paper, we model brain age predicted by cortical thickness data gathered from
      large cohort brain images. We collected 2,911 cognitively normal subjects (age 45
      91 years) at a single medical center and acquired their brain magnetic resonance
      (MR) images. All images were acquired using the same scanner with the same
      protocol. We propose to first apply Sparse Group Lasso (SGL) for feature
      selection by utilizing the brain's anatomical grouping. Once the features are
      selected, a non-parametric non-linear regression using the Gaussian Process
      Regression (GPR) algorithm is applied to fit the final age prediction model.
      Experimental results demonstrate that the proposed method achieves the mean
      absolute error of 4.05 years, which is comparable with or superior to several
      recent methods. Our method can also be a critical tool for clinicians to
      differentiate patients with neurodegenerative brain disease by extracting a
      cortical thinning pattern associated with normal aging.

PMID- 30186152
TI  - Automation vs. Experience: Measuring Alzheimer's Beta-Amyloid 1-42 Peptide in the
      CSF.
AB  - Cerebrospinal fluid (CSF) biomarkers can enhance the early and accurate etiologic
      detection of Alzheimer's disease (AD) even when symptoms are very mild, but are
      not yet widely available for clinical testing. There are a number of reasons for
      this, including the need for an experienced operator, the use of instruments
      mostly reserved for research, and low cost-effectiveness when patient samples do
      not completely fill each assay plate. Newer technology can overcome some of these
      issues through automated assays of a single patient sample on existing clinical
      laboratory platforms, but it is not known how these newer automated assays
      compare with previous research-based measurements. This is a critical issue in
      the clinical translation of CSF AD biomarkers because most cohort and
      clinicopathologic studies have been analyzed on older assays. To determine the
      correlation of CSF beta-amyloid 1-42 (Abeta42) measures derived from the
      automated chemiluminescent enzyme immunoassay (CLEIA, on Lumipulse(r) G1200), a
      bead-based Luminex immunoassay, and a plate-based enzyme-linked immunoassay
      enzyme-linked immunosorbent assay (ELISA), we analyzed 30 CSF samples weekly on
      each platforms over 3 weeks. We found that, while CSF Abeta42 levels were
      numerically closer between CLEIA and ELISA measurements, levels differed between
      all three assays. CLEIA-based measures correlated linearly with the two other
      assays in the low and intermediate Abeta42 concentrations, while there was a
      linear correlation between Luminex assay and ELISA throughout all concentrations.
      For repeatability, the average intra-assay coefficient of variation (CV) was
      2.0%. For intermediate precision, the inter-assay CV was lower in CLEIA (7.1%)
      than Luminex (10.7%, p = 0.009) and ELISA (10.8%, p = 0.009), primarily due to
      improved intermediate precision in the higher CSF Abeta42 concentrations. We
      conclude that the automated CLEIA generated reproducible CSF Abeta42 measures
      with improved intermediate precision over experienced operators using Luminex
      assays and ELISA, and are highly correlated with the manual Abeta42 measures.

PMID- 30186153
TI  - Expression Pattern of Myelin-Related Apolipoprotein D in Human Multiple Sclerosis
      Lesions.
AB  - Apolipoprotein D (Apo D) is a key molecule in the lipid transport during
      homeostasis and repair processes in normal and pathological conditions of the
      nervous system with a putative neuroprotective effect. In the last decades, huge
      experimental efforts have been made to know the exact mechanism of action of Apo
      D, even though, it remains an open question. In this regard, studies in mammals
      and flies have suggested that Apo D seems to act through a variety of cellular
      mechanisms related with its ability to selectively bind different lipid ligands.
      For instance, this apolipoprotein is required to myelin compaction, it
      participates in axon regeneration/remyelination, and it can control the magnitude
      and timing of the inflammatory response after injury, promoting myelin clearance,
      and regulating the number of immune cells recruited to the damaged area. These,
      among others, are some of the reasons to study Apo D in multiple sclerosis (MS)
      pathology, where it could be particularly important since the autoimmune reaction
      against oligodendrocytes (OLGs) and myelin is generally assumed as the most
      plausible cause of this pathology. The aim of this work was to investigate the
      Apo D expression pattern in MS lesions, including active and inactive
      demyelinating plaques, and also remyelinating ones. Human brain tissues with
      inflammatory demyelination consistent with MS were used to quantify Apo D
      immunosignal in different lesions. Our results show a clear decrease of Apo D
      expression in all sclerosis plaques, being lower in the inactive than in active
      areas but recovers in the remyelination ones. Apo D is mainly produced by the
      matured OLGs of white matter and is located in cell processes surrounding the
      myelin sheath. All these data seem to indicate an important role of Apo D in
      myelination/remyelination processes as a molecule with a neuroprotective
      potential, and may serve as a good starting point for its study in MS.

PMID- 30186155
TI  - Effects of Gender and Apolipoprotein E on Novelty MMN and P3a in Healthy Elderly
      and Amnestic Mild Cognitive Impairment.
AB  - Background: The apolipoprotein E epsilon4 (ApoE epsilon4) allele and female
      gender may be important risk factors for the development of Alzheimer's disease
      and amnestic mild cognitive impairment (aMCI). Novelty mismatch negativity (MMN)
      represents the pre-attentive index of deviance detection and P3a represents the
      attention orienting response. Furthermore, MMN and P3a components have been
      reported to be potential markers in aMCI. Therefore, this study will investigate
      the effects of gender and ApoE on auditory novelty MMN and P3a and their
      relationship to neuropsychological performance in aMCI. Methods: Thirty nine aMCI
      subjects and 44 controls underwent neuropsychological assessment and ApoE
      genotyping. Novelty MMN and P3a components were investigated during an auditory
      novelty oddball task. Results: Firstly, novelty MMN latency was significantly
      shorter in aMCI than in healthy control (HC) group. Secondly, novelty MMN latency
      was negatively correlated with episodic memory in aMCI, but not in HC. Novelty
      P3a latency was negatively correlated with information processing speed in all
      subjects. For gender effect, novelty MMN latency was shorter in aMCI females than
      in HC females. Moreover, novelty P3a amplitudes were lower in males than in
      females in both aMCI and HC. For the effect of ApoE status, novelty MMN latency
      was shorter in aMCI ApoE epsilon4- than HC ApoE epsilon4-. Conclusion: aMCI
      presents altered pre-attentive processing indexed by novelty MMN components.
      Furthermore, there may be a compensatory mechanism on the impaired processing in
      aMCI. It further suggests that aMCI female and ApoE epsilon4- recruited the
      compensatory mechanism.

PMID- 30186154
TI  - Cognitive Reserve Relates to Functional Network Efficiency in Alzheimer's
      Disease.
AB  - Alzheimer's disease (AD) is the most common form of dementia, with no means of
      cure or prevention. The presence of abnormal disease-related proteins in the
      population is, in turn, much more common than the incidence of dementia. In this
      context, the cognitive reserve (CR) hypothesis has been proposed to explain the
      discontinuity between pathophysiological and clinical expression of AD,
      suggesting that CR mitigates the effects of pathology on clinical expression and
      cognition. fMRI studies of the human connectome have recently reported that AD
      patients present diminished functional efficiency in resting-state networks,
      leading to a loss in information flow and cognitive processing. No study has
      investigated, however, whether CR modifies the effects of the pathology in
      functional network efficiency in AD patients. We analyzed the relationship
      between CR, pathophysiology and network efficiency, and whether CR modifies the
      relationship between them. Fourteen mild AD, 28 amnestic mild cognitive
      impairment (aMCI) due to AD, and 28 controls were enrolled. We used education to
      measure CR, cerebrospinal fluid (CSF) biomarkers to evaluate pathophysiology, and
      graph metrics to measure network efficiency. We found no relationship between CR
      and CSF biomarkers; CR was related to higher network efficiency in all groups;
      and abnormal levels of CSF protein biomarkers were related to more efficient
      networks in the AD group. Education modified the effects of tau-related pathology
      in the aMCI and mild AD groups. Although higher CR might not protect individuals
      from developing AD pathophysiology, AD patients with higher CR are better able to
      cope with the effects of pathology-presenting more efficient networks despite
      pathology burden. The present study highlights that interventions focusing on
      cognitive stimulation might be useful to slow age-related cognitive decline or
      dementia and lengthen healthy aging.

PMID- 30186156
TI  - The Potential of LPS-Binding Protein to Reverse Amyloid Formation in Plasma
      Fibrin of Individuals With Alzheimer-Type Dementia.
AB  - Many studies indicate that there is a (mainly dormant) microbial component in the
      progressive development of Alzheimer-type dementias (ADs); and that in the case
      of Gram-negative organisms, a chief culprit might be the shedding of the highly
      inflammagenic lipopolysaccharide (LPS) from their cell walls. We have recently
      shown that a highly sensitive assay for the presence of free LPS [added to
      platelet poor plasma (PPP)] lies in its ability (in healthy individuals) to
      induce blood to clot into an amyloid form. This may be observed in a SEM or in a
      confocal microscope when suitable amyloid stains (such as thioflavin T) are
      added. This process could be inhibited by human lipopolysaccharide-binding
      protein (LBP). In the current paper, we show using scanning electron microscopy
      and confocal microscopy with amyloid markers, that PPP taken from individuals
      with AD exhibits considerable amyloid structure when clotting is initiated with
      thrombin but without added LPS. Furthermore, we could show that this amyloid
      structure may be reversed by the addition of very small amounts of LBP. This
      provides further evidence for a role of microbes and their inflammagenic cell
      wall products and that these products may be involved in pathological clotting in
      individuals with AD.

PMID- 30186157
TI  - Berberine: Botanical Occurrence, Traditional Uses, Extraction Methods, and
      Relevance in Cardiovascular, Metabolic, Hepatic, and Renal Disorders.
AB  - Berberine-containing plants have been traditionally used in different parts of
      the world for the treatment of inflammatory disorders, skin diseases, wound
      healing, reducing fevers, affections of eyes, treatment of tumors, digestive and
      respiratory diseases, and microbial pathologies. The physico-chemical properties
      of berberine contribute to the high diversity of extraction and detection
      methods. Considering its particularities this review describes various methods
      mentioned in the literature so far with reference to the most important factors
      influencing berberine extraction. Further, the common separation and detection
      methods like thin layer chromatography, high performance liquid chromatography,
      and mass spectrometry are discussed in order to give a complex overview of the
      existing methods. Additionally, many clinical and experimental studies suggest
      that berberine has several pharmacological properties, such as immunomodulatory,
      antioxidative, cardioprotective, hepatoprotective, and renoprotective effects.
      This review summarizes the main information about botanical occurrence,
      traditional uses, extraction methods, and pharmacological effects of berberine
      and berberine-containing plants.

PMID- 30186158
TI  - Use of Some Asteraceae Plants for the Treatment of Wounds: From
      Ethnopharmacological Studies to Scientific Evidences.
AB  - Severe wounds result in large lesions and/or loss of function of the affected
      areas. The treatment of wounds has challenged health professionals due to its
      complexity, especially in patients with chronic diseases (such as diabetes), and
      the presence of pathogens such as Staphylococcus aureus and Pseudomonas
      aeruginosa. Taking this into consideration, the development of new therapies for
      wound healing requires immediate attention. Ethnopharmacological studies
      performed in different countries have shown the use of several plants from the
      Asteraceae family as wound-healing agents. Evidences gained from the traditional
      medicine have opened new ways for the development of novel and more efficient
      therapies based on the pharmacological properties of these plants. In this
      article, we discuss the literature data on the use of Asteraceae plants for the
      treatment of wounds, based on the ethnopharmacological relevance of each plant.
      Special attention was given to studies showing the mechanisms of action of
      Asteraceae-derived compounds and clinical trials. Ageratina pichinchensis (Kunth)
      R.M. King and H. Rob. and Calendula officinalis L. preparations/compounds were
      found to show good efficacy when assessed in clinical trials of complicated
      wounds, including venous leg ulcers and foot ulcers of diabetic patients. The
      compounds silibinin [from Silybum marianum (L.) Gaertn.] and jaceosidin (from
      Artemisia princeps Pamp.) were identified as promising compounds for the
      treatment of wounds. Overall, we suggest that Asteraceae plants represent
      important sources of compounds that may act as new and efficient healing
      products.

PMID- 30186159
TI  - The Curcumin Analogs 2-Pyridyl Cyclohexanone Induce Apoptosis via Inhibition of
      the JAK2-STAT3 Pathway in Human Esophageal Squamous Cell Carcinoma Cells.
AB  - Multiple modifications to the structure of curcumin have been investigated with
      an aim to improve its potency and biochemical properties. Previously, we have
      synthesized a series of curcumin analogs. In the present study, the anticancer
      effect of 2-pyridyl cyclohexanone, one of the curcumin analogs, on esophageal
      carcinoma Eca109 and EC9706 cell lines and its molecular mechanisms were
      investigated. 2-Pyridyl cyclohexanone inhibited the proliferation of Eca109 and
      EC9706 cells by inducing apoptosis as indicated by morphological changes,
      membrane phospholipid phosphatidylserine ectropion, caspase 3 activation, and
      cleavage of poly(ADP-ribose) polymerase. Mechanistic studies indicated that 2
      pyridyl cyclohexanone disrupted mitochondrial membrane potential, disturbed the
      balance of the Bcl-2 family proteins, and triggered apoptosis via the
      mitochondria-mediated intrinsic pathway. In 2-pyridine cyclohexanone-treated
      cells, the phosphorylation levels of JAK2 and STAT3 were dose-dependently
      decreased and p38 and p-ERK signals were notably activated in a dose-dependent
      manner. Moreover, we found that the addition of S3I-201, a STAT3 inhibitor, led
      to a decreased expression level of Bcl-2 in Eca109 cells. The chromatin
      immunoprecipitation assay demonstrated that STAT3 bound to the promoter of Bcl-2
      in the Eca109 cells. Furthermore, the mutation of four STAT3 binding sites (
      1733/-1723, -1627/-1617, -807/-797, and -134/-124) on the promote of Bcl-2 gene
      alone attenuated the transcriptional activation of STAT3. In addition, down
      regulation of STAT3 resulted in less of transcriptional activity of STAT3 on Bcl
      2 expression. These data provide a potential molecular mechanism of the apoptotic
      induction function of 2-pyridyl cyclohexanone, and emphasize its important roles
      as a therapeutic agent for esophageal squamous carcinoma.

PMID- 30186160
TI  - The Reproductive Toxicity of Mequindox in a Two-Generation Study in Wistar Rats.
AB  - Mequindox (MEQ), belonging to quinoxaline-di-N-oxides (QdNOs), has been
      extensively used as a synthetic antibacterial agent. To evaluate the reproductive
      toxicity of MEQ, different concentrations of MEQ were administered to Wistar rats
      by feeding diets containing 0, 25, 55, 110, and 275 mg/kg, respectively. Each
      group consisting of 25 males and 25 females (F0) was treated with different
      concentrations of MEQ for 12-week period time, prior to mating and during mating,
      gestation, parturition and lactation. At weaning, 25 males and 25 females of F1
      generation weanlings per group were randomly selected as parents for the F2
      generation. Selected F1 weanlings were exposed to the same diet and treatment as
      their parents. The number of live litter and indexes of mating and fertility were
      significantly decreased in the F1 and F2 generation at 110 and 275 mg/kg groups.
      Significant decrease in pup vitality during lactation was observed in F1 litter
      at 275 mg/kg group, in F2 litter at 55, 110, and 275 mg/kg groups. A downward
      trend in the body weights was observed in F1 pups at 55, 110, and 275 mg/kg MEQ
      groups, and in F2 pups at 110 and 275 mg/kg MEQ groups. The changed levels of
      ALT, AST, CREA, BUN, UA, Na, and K were noted in the serum of rats. The
      histopathologic examination showed that MEQ induced toxicity in the liver,
      kidney, adrenal, uterus and testis. The no-observed-adverse-effect level (NOAEL)
      for reproduction toxicity of MEQ was 25 mg/kg diet. The malformations and severe
      maternal toxicity of MEQ caused adverse effects on the conceptus and embryo,
      which result in fetal malformations and fetal deaths. In summary, the present
      study showed that MEQ induced maternal, embryo and reproductive toxicities as
      well as teratogenicity in rats.

PMID- 30186161
TI  - Analysis of the Metabolic Characteristics of Serum Samples in Patients With
      Multiple Myeloma.
AB  - Aims: This study aimed to identify potential, non-invasive biomarkers for
      diagnosis and monitoring of the progress in multiple myeloma (MM) patients.
      Methods: MM patients and age-matched healthy controls (HC) were recruited in
      Discovery phase and Validation phase, respectively. MM patients were segregated
      into active group (AG) and responding group (RG). Serum samples were collected
      were conducted to non-targeted metabolomics analyses. Metabolites which were
      significantly changed (SCMs) among groups were identified in Discovery phase and
      was validated in Validation phase. The signaling pathways of these SCMs were
      enriched. The ability of SCMs to discriminate among groups in Validation phase
      was analyzed through receiver operating characteristic curve. The correlations
      between SCMs and clinical features, between SCMs and survival period of MM
      patients were analyzed. Results: Total of 23 SCMs were identified in AG compared
      with HC both in Discovery phase and Validation phase. Those SCMs were
      significantly enriched in arginine and proline metabolism and glycerophospholipid
      metabolism. 4 SCMs had the discriminatory ability between MM patients and healthy
      controls in Validation phase. Moreover, 12 SCMs had the ability to discriminate
      between the AG patients and RG patients in Validation phase. 10 out of 12 SCMs
      correlated with advanced features of MM. Moreover, 8 out of 12 SCMs had the
      negative impact on the survival of MM. 5'-Methylthioadenosine may be the only
      independent prognostic factor in survival period of MM. Conclusion: 10 SCMs
      identified in our study, which correlated with advanced features of MM, could be
      potential, novel, non-invasive biomarkers for active disease in MM.

PMID- 30186163
TI  - Inhibition of Chloride Intracellular Channel 1 (CLIC1) as Biguanide Class-Effect
      to Impair Human Glioblastoma Stem Cell Viability.
AB  - The antidiabetic biguanide metformin exerts antiproliferative effects in
      different solid tumors. However, during preclinical studies, metformin
      concentrations required to induce cell growth arrest were invariably within the
      mM range, thus difficult to translate in a clinical setting. Consequently, the
      search for more potent metformin derivatives is a current goal for new drug
      development. Although several cell-specific intracellular mechanisms contribute
      to the anti-tumor activity of metformin, the inhibition of the chloride
      intracellular channel 1 activity (CLIC1) at G1/S transition is a key events in
      metformin antiproliferative effect in glioblastoma stem cells (GSCs). Here we
      tested several known biguanide-related drugs for the ability to affect
      glioblastoma (but not normal) stem cell viability, and in particular: phenformin,
      a withdrawn antidiabetic drug; moroxydine, a former antiviral agent; and
      proguanil, an antimalarial compound, all of them possessing a linear biguanide
      structure as metformin; moreover, we evaluated cycloguanil, the active form of
      proguanil, characterized by a cyclized biguanide moiety. All these drugs caused a
      significant impairment of GSC proliferation, invasiveness, and self-renewal
      reaching IC50 values significantly lower than metformin, (range 0.054-0.53 mM vs.
      9.4 mM of metformin). All biguanides inhibited CLIC1-mediated ion current,
      showing the same potency observed in the antiproliferative effects, with the
      exception of proguanil which was ineffective. These effects were specific for
      GSCs, since no (or little) cytotoxicity was observed in normal umbilical cord
      mesenchymal stem cells, whose viability was not affected by metformin and
      moroxydine, while cycloguanil and phenformin induced toxicity only at much higher
      concentrations than required to reduce GSC proliferation or invasiveness.
      Conversely, proguanil was highly cytotoxic also for normal mesenchymal stem
      cells. In conclusion, the inhibition of CLIC1 activity represents a biguanide
      class-effect to impair GSC viability, invasiveness, and self-renewal, although
      dissimilarities among different drugs were observed as far as potency, efficacy
      and selectivity as CLIC1 inhibitors. Being CLIC1 constitutively active in GSCs,
      this feature is relevant to grant the molecules with high specificity toward GSCs
      while sparing normal cells. These results could represent the basis for the
      development of novel biguanide-structured molecules, characterized by high
      antitumor efficacy and safe toxicological profile.

PMID- 30186164
TI  - Cannabidiol Administered During Peri-Adolescence Prevents Behavioral
      Abnormalities in an Animal Model of Schizophrenia.
AB  - Schizophrenia is considered a debilitating neurodevelopmental psychiatric
      disorder and its pharmacotherapy remains problematic without recent major
      advances. The development of interventions able to prevent the emergence of
      schizophrenia would therefore represent an enormous progress. Here, we
      investigated whether treatment with cannabidiol (CBD - a compound of Cannabis
      sativa that presents an antipsychotic profile in animals and humans) during peri
      adolescence would prevent schizophrenia-like behavioral abnormalities in an
      animal model of schizophrenia: the spontaneously hypertensive rat (SHR) strain.
      Wistar rats and SHRs were treated with vehicle or CBD from 30 to 60 post-natal
      days. In experiment 1, schizophrenia-like behaviors (locomotor activity, social
      interaction, prepulse inhibition of startle and contextual fear conditioning)
      were assessed on post-natal day 90. Side effects commonly associated with
      antipsychotic treatment were also evaluated: body weight gain and catalepsy
      throughout the treatment, and oral dyskinesia 48 h after treatment interruption
      and on post-natal day 90. In experiment 2, serum levels of triglycerides and
      glycemia were assessed on post-natal day 61. In experiment 3, levels of BDNF,
      monoamines, and their metabolites were evaluated on post-natal days 61 and 90 in
      the prefrontal cortex and striatum. Treatment with CBD prevented the emergence of
      SHRs' hyperlocomotor activity (a model for the positive symptoms of
      schizophrenia) and deficits in prepulse inhibition of startle and contextual fear
      conditioning (cognitive impairments). CBD did not induce any of the potential
      motor or metabolic side effects evaluated. Treatment with CBD increased the
      prefrontal cortex 5-HIAA/serotonin ratio and the levels of 5-HIAA on post-natal
      days 61 and 90, respectively. Our data provide pre-clinical evidence for a safe
      and beneficial effect of peripubertal and treatment with CBD on preventing
      positive and cognitive symptoms of schizophrenia, and suggest the involvement of
      the serotoninergic system on this effect.

PMID- 30186165
TI  - Association Between BRCA Status and Triple-Negative Breast Cancer: A Meta
      Analysis.
AB  - Triple-negative breast cancer (TNBC) is a subtype of aggressive breast cancer and
      characterized by a lack of the expression of estrogen receptor, progesterone
      receptor and human epidermal growth factor receptor 2. BRCA genes are tumor
      suppressor genes that are involved in DNA damage repair and mutations of BRCA
      genes may increase the risk of developing breast cancer and/or ovarian cancer due
      to defective DNA repair mechanisms. However, the relationship between BRCA status
      and TNBC needs to be further investigated and validated. The aim of this meta
      analysis was to evaluate the association between BRCA status and TNBC. We
      systematically searched the electronic databases of MEDLINE (PubMed), Embase, and
      Cochrane Library to identify relevant publications from April, 1959 to November,
      2017. The data from the studies were examined by a meta-analysis using STATA
      software to calculate the odds ratio (OR) with 95% confidence interval (CI) by
      fixed-effect and random-effect models. We identified 16 qualified studies from
      527 publications with 46,870 breast cancer patients including 868 BRCA1 mutations
      (BRCA1Mut ) carriers, 739 BRCA2 mutations (BRCA2Mut ) carriers, and 45,263 non
      carriers. The results showed that breast cancer patients with BRCA1Mut carriers
      were more likely to have TNBC than those of BRCA2Mut carriers (OR: 3.292; 95% CI:
      2.773-3.909) or non-carriers (OR: 8.889; 95% CI: 6.925-11.410). Furthermore, high
      expression of nuclear grade and large tumor burden (>2 cm) were significantly
      more common in breast cancer patients with BRCA1Mut carriers than those of
      BRCA2Mut carriers (OR: 2.663; 95% CI: 1.731-4.097; P = 0.211) or non-carriers
      (OR: 1.577; 95% CI: 1.067-2.331; P = 0.157). The data suggest that breast cancer
      patients with BRCA1Mut are more likely to have TNBC, high nuclear grade, and
      larger tumor burden.

PMID- 30186167
TI  - Beneficial Role of Rosuvastatin in Blood-Brain Barrier Damage Following
      Experimental Ischemic Stroke.
AB  - Hemorrhage transformation is the most challenging preventable complication in
      thrombolytic therapy and is related to recombinant tissue plasminogen activator
      (rt-PA)-induced blood-brain barrier (BBB) damage. Intraperitoneal injections of
      normal or high doses of rosuvastatin were administered to Balb/c mice 20 min
      prior to middle cerebral artery occlusion (MCAO) surgery for 3 h followed by
      reperfusion with rt-PA thrombolytic therapy and cerebral blood flow monitoring to
      investigate whether a high or normal dose of rosuvastatin reduces BBB damage
      after brain ischemia and rt-PA reperfusion. The integrity of the BBB was
      ameliorated by normal and high doses of rosuvastatin as determined from Evans
      blue staining, ultrastructure assessments and immunochemistry at 24 h after
      reperfusion. The levels of TJ proteins were preserved, potentially by targeting
      platelet-derived growth factor receptor alpha (PDGFR-alpha) and low-density
      lipoprotein receptor-related protein 1 (LRP1) to inhibit the expression of matrix
      metalloproteinase proteins (MMPs) by reducing the levels of phosphorylated c-jun
      N-terminal kinase (pJNK), phosphorylated mitogen-activated protein kinase (MAPK)
      p38 (pP38) and increasing the levels of phosphorylated extracellular regulated
      protein kinases (pERK), and tissue inhibitor of metalloproteinases (TIMPs), as
      inferred from Western blotting and molecular docking analyses. In summary,
      rosuvastatin reduced rt-PA therapy-associated BBB permeability by PDGFR-alpha-
      and LRP1-associated MAPK pathways to reduce the mortality of mice, and a normal
      dose of rosuvastatin exerted greater preventative effects on reducing BBB damage
      than did a high dose in the time window of thrombolytic therapy.

PMID- 30186162
TI  - Spice-Derived Bioactive Ingredients: Potential Agents or Food Adjuvant in the
      Management of Diabetes Mellitus.
AB  - Spices possess tremendous therapeutic potential including hypoglycemic action,
      attributed to their bioactive ingredients. However, there is no study that
      critically reviewed the hypoglycemic potency, safety and the bioavailability of
      the spice-derived bioactive ingredients (SDBI). Therefore, the aim of the study
      was to comprehensively review all published studies regarding the hypoglycemic
      action of SDBI with the purpose to assess whether the ingredients are potential
      hypoglycemic agents or adjuvant. Factors considered were concentration/dosages
      used, the extent of blood glucose reduction, the IC50 values, and the safety
      concern of the SDBI. From the results, cinnamaldehyde, curcumin, diosgenin,
      thymoquinone (TQ), and trigonelline were showed the most promising effects and
      hold future potential as hypoglycemic agents. Conclusively, future studies should
      focus on improving the tissue and cellular bioavailability of the promising SDBI
      to achieve greater potency. Additionally, clinical trials and toxicity studies
      are with these SDBI are warranted.

PMID- 30186166
TI  - Bridging Molecular Docking to Molecular Dynamics in Exploring Ligand-Protein
      Recognition Process: An Overview.
AB  - Computational techniques have been applied in the drug discovery pipeline since
      the 1980s. Given the low computational resources of the time, the first molecular
      modeling strategies relied on a rigid view of the ligand-target binding process.
      During the years, the evolution of hardware technologies has gradually allowed
      simulating the dynamic nature of the binding event. In this work, we present an
      overview of the evolution of structure-based drug discovery techniques in the
      study of ligand-target recognition phenomenon, going from the static molecular
      docking toward enhanced molecular dynamics strategies.

PMID- 30186169
TI  - Ileal Bile Acid Transporter Inhibition for the Treatment of Chronic Constipation,
      Cholestatic Pruritus, and NASH.
AB  - Bile acids are synthesized from cholesterol in the liver, excreted with bile into
      the duodenum, almost completely taken up again in the distal ileum and finally
      returned to the liver with portal blood in a process termed enterohepatic
      circulation. Bile acid synthesis, excretion, and reuptake are tightly regulated.
      The apical sodium-dependent bile acid transporter [ASBT; also known as ileal bile
      acid transporter (IBAT) and SLC10A2] is pivotal for the almost complete
      reabsorption of conjugated bile acids in the ileum. Dysfunctional IBAT may be the
      cause of bile acid diarrhea. Pharmacological IBAT inhibition results in an
      increased bile acid load in the colon and subsequently a lower bile acid pool,
      which is associated with improved liver histology in animal models of cholestatic
      liver disease and non-alcoholic steatohepatitis (NASH). In humans, IBAT
      inhibitors have been tested in clinical trials with widely different indications:
      in patients with idiopathic chronic constipation, an increased number of bowel
      movements was observed. In adult and pediatric cholestatic liver diseases with
      pruritus, various IBAT inhibitors showed potential to improve itching. Adverse
      events of IBAT inhibitors, based on their mode of action, are abdominal pain and
      diarrhea which might patients to withdraw from study medications. So far, no data
      are available of a study of IBAT inhibitors in patients with NASH. In this review
      we summarize the preclinical and most recent clinical studies with various IBAT
      inhibitors and discuss the difficulties that should be addressed in future
      studies.

PMID- 30186168
TI  - Cell-Specific Protective Signaling Induced by the Novel AT2R-Agonist NP-6A4 on
      Human Endothelial and Smooth Muscle Cells.
AB  - Cardiovascular disease incidence continues to rise and new treatment paradigms
      are warranted. We reported previously that activation of Angiotensin II receptor
      (encoded by the X-linked Agtr2 gene) by a new peptide agonist, NP-6A4, was more
      effective in protecting mouse cardiomyocyte HL-1 cells and human coronary artery
      vascular smooth muscle cells (hCAVSMCs) from acute nutrient deficiency than other
      drugs tested. To elucidate further the protective effects of NP-6A4 in human
      cells, we studied the effects of NP-6A4 treatment on functions of human coronary
      artery endothelial cells (hCAECs), and hCAVSMCs. In hCAVSMCs, NP-6A4 (1 MUM)
      increased Agtr2 mRNA (sixfold, p < 0.05) after 12-h exposure, whereas in hCAECs,
      significant increase in Agtr2 mRNA (hCAECs: eightfold) was observed after
      prolonged exposure. Interestingly, NP-6A4 treatment (1 MUM, 12 h) increased AT2R
      protein levels in all human cells tested. Pre-treatment with AT2R-antagonist
      PD123319 (20 MUM) and anti-AT2R siRNA (1 MUM) suppressed this effect. Thus, NP
      6A4 activates a positive feedback loop for AT2R expression and signaling in
      hCAVSMCs and hCAECs. NP-6A4 (1-20 MUM) increased cell index (CI) of hCAVSMCs as
      determined by real time cell analyzer (RTCA), indicating that high concentrations
      of NP-6A4 were not cytotoxic for hCAVSMCs, rather promoting better cell
      attachment and growth. Seahorse Extracellular Flux Assay revealed that NP-6A4 (1
      MUM) treatment for 7 days increased whole cell-based mitochondrial parameters of
      hCAVSMCs, specifically maximal respiration (p < 0.05), spare respiratory capacity
      (p < 0.05) and ATP production (p < 0.05). NP-6A4 (1 MUM; 7 days) also suppressed
      Reactive Oxygen Species (ROS) in hCAVSMCs. Exposure to Doxorubicin (DOXO) (1 MUM)
      increased ROS in hCAVSMCs and this effect was suppressed by NP-6A4 (1 MUM). In
      hCAECs grown in complete medium, NP-6A4 (1 MUM) and Ang II (1 MUM) exerted
      similar changes in CI. Additionally, NP-6A4 (5 MUM: 12 h) increased expression of
      eNOS (sixfold, p < 0.05) and generation of nitric oxide (1.3-fold, p < 0.05) in
      hCAECs and pre-treatment with PD123319 (20 MUM) suppressed this effect partially
      (65%). Finally, NP-6A4 decreased phosphorylation of Jun-N-terminal kinase,
      implicated in apoptosis of ECs in atherosclerotic sites. Taken together, NP-6A4,
      through its ability to increase AT2R expression and signaling, exerts different
      cell-specific protective effects in human VSMCs and ECs.

PMID- 30186170
TI  - A Metabolomics Study on the Bone Protective Effects of a Lignan-Rich Fraction
      From Sambucus Williamsii Ramulus in Aged Rats.
AB  - The lignan-rich fraction (SWR) of Sambucus Williamsii Ramulus, a folk herbal
      medicine in China for treatment of bone diseases, has previously reported to
      exert protective effects on bone without exerting uterotrophic effects in
      ovariectomized (OVX) mice. The aim of the present study was to identify the
      potential metabolites and the associated metabolic pathways that contribute to
      the beneficial effects of SWR on bone in vivo. Aged female Sprague Dawley rats (9
      months old) were either sham-operated or ovariectomized for 12 weeks, before
      receiving treatment for another 12 weeks with the following treatment groups (n =
      12 each): vehicle (Sham), vehicle (OVX), Premarin (130 MUg/kg) or low (57 mg/kg),
      medium (114 mg/kg), and high (228 mg/kg) doses of SWR. The results showed that
      SWRH significantly suppressed bone loss, improved bone micro-architecture and
      increased bone strength on tibia without stimulating uterus weight gain in OVX
      rats. Premarin exerted similar bone protective effects as SWRH but elicited
      uterotrophic effects in OVX rats. The metabolic profiles of serum samples were
      analyzed by using ultra-performance liquid chromatography quadrupole time-of
      flight mass spectrometry and gas chromatography time-of flight mass spectrometry,
      and the metabolites that were significantly altered were identified by
      multivariate statistical analysis. Our study indicated that SWRH effectively
      restored the changes of 26 metabolites induced by estrogen-deficiency in OVX
      rats, which related to lipids, amino acids, tryptophan metabolisms, and anti
      oxidative system. A subsequent validation showed that the serum level of
      superoxide dismutase and catalase were indeed up-regulated, while the serotonin
      level in a tryptophan hydroxylase 1 (TPH1) high expressing cells (rats RBL-2H3
      cells) was down regulated after treatment with SWR. The results also suggested
      that the gut-microbiota may play an important role on the bone protective effects
      of SWR. The current study provides insight for understanding the unique mechanism
      of actions of SWR that might be involved in achieving bone protective effects in
      vivo.

PMID- 30186171
TI  - Distinct Occurrence of Proarrhythmic Afterdepolarizations in Atrial Versus
      Ventricular Cardiomyocytes: Implications for Translational Research on Atrial
      Arrhythmia.
AB  - Background: Principal mechanisms of arrhythmia have been derived from ventricular
      but not atrial cardiomyocytes of animal models despite higher prevalence of
      atrial arrhythmia (e.g., atrial fibrillation). Due to significant ultrastructural
      and functional differences, a simple transfer of ventricular proneness toward
      arrhythmia to atrial arrhythmia is critical. The use of murine models in
      arrhythmia research is widespread, despite known translational limitations. We
      here directly compare atrial and ventricular mechanisms of arrhythmia to identify
      critical differences that should be considered in murine models for development
      of antiarrhythmic strategies for atrial arrhythmia. Methods and Results: Isolated
      murine atrial and ventricular myocytes were analyzed by wide field microscopy and
      subjected to a proarrhythmic protocol during patch-clamp experiments. As
      expected, the spindle shaped atrial myocytes showed decreased cell area and
      membrane capacitance compared to the rectangular shaped ventricular myocytes.
      Though delayed afterdepolarizations (DADs) could be evoked in a similar fraction
      of both cell types (80% of cells each), these led significantly more often to the
      occurrence of spontaneous action potentials (sAPs) in ventricular myocytes.
      Interestingly, numerous early afterdepolarizations (EADs) were observed in the
      majority of ventricular myocytes, but there was no EAD in any atrial myocyte
      (EADs per cell; atrial myocytes: 0 +/- 0; n = 25/12 animals; ventricular
      myocytes: 1.5 [0-43]; n = 20/12 animals; p < 0.05). At the same time, the action
      potential duration to 90% decay (APD90) was unaltered and the APD50 even
      increased in atrial versus ventricular myocytes. However, the depolarizing L-type
      Ca2+ current (ICa) and Na+/Ca2+-exchanger inward current (INCX) were
      significantly smaller in atrial versus ventricular myocytes. Conclusion: In mice,
      atrial myocytes exhibit a substantially distinct occurrence of proarrhythmic
      afterdepolarizations compared to ventricular myocytes, since they are in a
      similar manner susceptible to DADs but interestingly seem to be protected against
      EADs and show less sAPs. Key factors in the generation of EADs like ICa and INCX
      were significantly reduced in atrial versus ventricular myocytes, which may offer
      a mechanistic explanation for the observed protection against EADs. These
      findings may be of relevance for current studies on atrial level in murine models
      to develop targeted strategies for the treatment of atrial arrhythmia.

PMID- 30186173
TI  - SOX2 Promotes Cell Proliferation and Metastasis in Triple Negative Breast Cancer.
AB  - This study explored the expression, biological function and prognostic role of
      SOX2 in triple negative breast cancer (TNBC). Quantitative real-time PCR and
      immunohistochemistry were used to detect the expression of SOX2 in TNBC cell
      lines and clinical tissues. MTT assay, Transwell assay, flow cytometry and
      xenograft mouse model were used to assess the biological functions of SOX2. It
      was found that SOX2 was up-regulated in both TNBC cell lines and clinical
      tissues. High expression of SOX2 was associated with shorter overall survival and
      disease free survival. Moreover, inhibition of SOX2 suppressed cell proliferation
      and invasion, induced cell apoptosis in vitro, and suppressed tumorigenesis and
      metastasis in vivo. In addition, analysis of TNM stage and lymph nodes
      infiltration among the 237 TNBC patients by paired chi2 test showed that SOX2 was
      inversely correlated with tumor status, our findings provided evidence that SOX2
      acts as a tumor promoter in TNBC and inhibition of SOX2 could be a potential
      therapeutic strategy for TNBC.

PMID- 30186172
TI  - Estrone-3-Sulfate Stimulates the Proliferation of T47D Breast Cancer Cells Stably
      Transfected With the Sodium-Dependent Organic Anion Transporter SOAT (SLC10A6).
AB  - : Estrogens play a pivotal role in the development and proliferation of hormone
      dependent breast cancer. Apart from free estrogens, which can directly activate
      the estrogen receptor (ER) of tumor cells, sulfo-conjugated steroids, which
      maintain high plasma concentrations even after menopause, first have to be
      imported into tumor cells by carrier-mediated uptake and then can be cleaved by
      the steroid sulfatase to finally activate ERs and cell proliferation. In the
      present study, expression of the sodium-dependent organic anion transporter SOAT
      was analyzed in breast cancer and its role for hormone-dependent proliferation of
      T47D breast cancer cells was elucidated. The SOAT protein was localized to the
      ductal epithelium of the mammary gland by immunohistochemistry. SOAT showed high
      expression in different pathologies of the breast with a clear ductal
      localization, including ductal hyperplasia, intraductal papilloma, and
      intraductal carcinoma. In a larger breast cancer cDNA array, SOAT mRNA expression
      was high in almost all adenocarcinoma specimen, but expression did not correlate
      with either the ER, progesterone receptor, or human epidermal growth factor
      receptor 2 status. Furthermore, SOAT expression did not correlate with tumor
      stage or grade, indicating widespread SOAT expression in breast cancer. To
      analyze the role of SOAT for breast cancer cell proliferation, T47D cells were
      stably transfected with SOAT and incubated under increasing concentrations of
      estrone-3-sulfate (E1S) and estradiol at physiologically relevant concentrations.
      Cell proliferation was significantly increased by 10-9 M estradiol as well as by
      E1S with EC50 of 2.2 nM. In contrast, T47D control cells showed 10-fold lower
      sensitivity to E1S stimulation with EC50 of 21.7 nM. The E1S-stimulated
      proliferation of SOAT-T47D cells was blocked by the SOAT inhibitor 4
      sulfooxymethylpyrene. IN CONCLUSION: The present study clearly demonstrates
      expression of SOAT in breast cancer tissue with ductal localization. SOAT
      inhibition can block the E1S-stimulated proliferation of T47D breast cancer
      cells, demonstrating that SOAT is an interesting novel drug target from the group
      of E1S uptake carriers for anti-proliferative breast cancer therapy.

PMID- 30186174
TI  - Periplaneta americana Ameliorates Dextran Sulfate Sodium-Induced Ulcerative
      Colitis in Rats by Keap1/Nrf-2 Activation, Intestinal Barrier Function, and Gut
      Microbiota Regulation.
AB  - Periplaneta americana, a magic medicinal insect being present for over 300
      million years, exhibits desirable therapeutic outcome for gastrointestinal ulcer
      treatment. Nowadays, P. americana ethanol extract (PAE) has been shown to
      ameliorate ulcerative colitis (UC) by either single-use or in combination with
      other therapeutic agents in clinics. However, its underlying mechanisms are still
      seldom known. Herein, we investigated the anti-UC activity of PAE by alleviating
      intestinal inflammation and regulating the disturbed gut microbiota structure in
      dextran sulfate sodium (DSS)-induced UC rats. Based on multiple constitute
      analyses by HPLC for quality control, PAE was administrated to DSS-induced UC
      rats by oral gavage for 2 weeks. The anti-UC effect of PAE was evaluated by
      inflammatory cytokine production, immunohistochemical staining, and gut
      microbiota analysis via 16S rRNA sequencing. As a result, PAE remarkably
      attenuated DSS-induced UC in rats. The colonic inflammatory responses manifested
      as decreased colonic atrophy, intestinal histopathology scores and inflammatory
      cytokines. In addition, PAE improved the intestinal barrier function via
      activating Keap1/Nrf-2 pathway and promoting the expressions of tight junction
      proteins. It was observed that the UC rats showed symptoms of gut microbial
      disturbance, i.e., the increased Firmicutes/Bacteroidetes ratio and the
      significantly decreased probiotics such as Lactobacillus, Roseburia, and
      Pectobacterium, which were negatively correlated with these detected pro
      inflammatory cytokines (secreted by immune CD4+ T cells, and including IFN-gamma,
      TNF-alpha, IL-6, IL-8, IL-17, IL-1beta). Besides, PAE administration regulated
      the abnormal intestinal microbial composition and made it similar to that in
      normal rats. Therefore, PAE could attenuate the DSS-induced UC in rats, by means
      of ameliorating intestinal inflammation, improving intestinal barrier function,
      and regulating the disturbed gut microbiota, especially improving beneficial
      intestinal flora growth, modulating the flora structure, and restoring the
      intestinal-immune system.

PMID- 30186175
TI  - Assessment of Wound-Healing Properties of Medicinal Plants: The Case of
      Phyllanthus muellerianus.
AB  - Phyllanthus muellerianus (Family Euphorbiaceae) is a shrub, which is widely
      distributed in West Africa and employed traditionally as a wound-healing agent
      especially in Ghana. The aim of the study was to determine the in vivo wound
      healing activity of aqueous aerial part extract of P. muellerianus (PLE) and its
      major isolate, geraniin. Excision and incision wound models were used to
      determine the wound-healing activity. Wounds were treated with PLE (0.25, 0.5,
      and 1% w/w) and geraniin (0.1, 0.2, and 0.4% w/w) aqueous creams. PLE and
      geraniin significantly (p < 0.001) increased wound contraction rate and
      hydroxyproline production compared to untreated wounds. Histological studies of
      wound tissues showed high levels of fibroblasts and increased collagen content
      and cross-linking in PLE and geraniin-treated wound tissues. Immuno-histochemical
      investigations revealed high levels of TGF-beta1 in PLE and geraniin-treated
      wound tissues compared to the untreated wound tissues. Tensile strength of
      incised wounds was significantly (p < 0.05) high in PLE and geraniin-treated
      wounds. PLE (0.1-100 MUg/mL) significantly (p < 0.001) reduce LDH release from
      HaCaT-keratinocytes compared to the untreated cells. PLE and geraniin possess
      wound healing and cytoprotective effect.

PMID- 30186176
TI  - The Role of Vitamin E in Preventing and Treating Osteoarthritis - A Review of the
      Current Evidence.
AB  - Osteoarthritis is a debilitating disease of the joint involving cartilage
      degeneration and chondrocytes apoptosis. Oxidative stress is one of the many
      proposed mechanisms underpinning joint degeneration in osteoarthritis. The
      current pharmacotherapies emphasize pain and symptomatic management of the
      patients but do not alter the biological processes underlying the cartilage
      degeneration. Vitamin E is a potential agent to prevent or treat osteoarthritis
      due to its antioxidant and anti-inflammatory effects. This review aims to
      summarize the current evidence on the relationship between vitamin E and
      osteoarthritis derived from preclinical and human studies. Cellular studies
      showed that vitamin E mitigated oxidative stress in cartilage explants or
      chondrocyte culture invoked by mechanical stress or free radicals. Animal studies
      suggested that vitamin E treatment prevented cartilage degeneration and improve
      oxidative status in animal models of osteoarthritis. Low circulating or synovial
      vitamin E was observed in human osteoarthritic patients compared to healthy
      controls. Observational studies also demonstrated that vitamin E was related to
      induction or progression of osteoarthritis in the general population. Vitamin E
      supplementation might improve the outcomes in patients with osteoarthritis, but
      negative results were also reported. Different isomers of vitamin E might possess
      distinct anti-osteoarthritic effects. As a conclusion, vitamin E may retard the
      progression of osteoarthritis by ameliorating oxidative stress and inflammation
      of the joint. Further studies are warranted to develop vitamin E as an anti
      osteoarthritis agent to reduce the global burden of this disease.

PMID- 30186177
TI  - Spheroid Size Does not Impact Metabolism of the beta-blocker Propranolol in 3D
      Intestinal Fish Model.
AB  - Compared to two-dimensional (2D) cell culture, cellular aggregates or spheroids
      (3D) offer a more appropriate alternative in vitro system where individual cell
      cell communication and micro-environment more closely represent the in vivo
      organ; yet we understand little of the physiological conditions at this scale.
      The relationship between spheroid size and oxygen microenvironment, an important
      factor influencing the metabolic capacity of cells, was first established using
      the fish intestine derived RTgutGC cell line. Subsequently, pharmaceutical
      metabolism (Propranolol), as determined by high performance liquid
      chromatography, in this intestinal model was examined as a function of spheroid
      size. Co-efficient of variation between spheroid size was below 12% using the
      gyratory platform method, with the least variation observed in the highest cell
      seeding density. The viable, high oxygen micro-environment of the outer rim of
      the spheroid, as determined by electron paramagnetic resonance (EPR) oximetry,
      decreased over time, and the hypoxic zone increased as a function of spheroid
      size. Despite a trend of higher metabolism in smaller spheroids, the formation of
      micro-environments (quiescent, hypoxic or anoxic) did not significantly affect
      metabolism or function of an environmentally relevant pharmaceutical in this
      spheroid model.

PMID- 30186178
TI  - An Optimized MicroPET Imaging Method for the Distribution and Synergies of
      Natural Products.
AB  - Purpose: Understanding the distribution and interaction of the Traditional
      Chinese Medicines (TCMs) is an integral source of herbal drug discovery. An
      optimized radio-labeled method was explored that could conduct in situ
      biodistribution studies in animals. We evaluated the feasibility of the method
      and applied glycyrrhetinic acid and platycodon (PG) polysaccharides as models.
      Procedures: [18F]-GA is a novel radiotracer which was performed positron emission
      tomography (PET) studies to assay the biodistribution of GA in mice. In addition,
      PG polysaccharide was used to intervene the biodistribution and dosimetry of GA.
      Scanning data were analyzed with professional software. Results: Record the time
      activity curves for all organs then use the normalization method to calculate the
      area under the curve as a dosimetry for each organ. Moreover, the addition of PG
      polysaccharides can significantly improve the dosimetry of GA in the lungs, and
      its effect was related to the administration time. Conclusion: MicroPET imaging
      opens up a new avenue for the application of drug interactions between the TCMs.

PMID- 30186179
TI  - Ginsenoside Rb1 and Rd Remarkably Inhibited the Hepatic Uptake of Ophiopogonin D
      in Shenmai Injection Mediated by OATPs/oatps.
AB  - Shenmai injection (SMI) is derived from traditional Chinese herbal prescription
      Shendong yin and widely used for treating cardiovascular diseases. Ophiopogonin D
      (OPD) is one of the main active components of SMI. The hepatic uptake of OPD is
      mediated by organic anion-transporting polypeptides (OATPs/oatps) and inhibited
      by some other components in SMI. This study aimed to identify the active
      components of SMI responsible for the inhibitory effects on hepatic uptake of OPD
      in rats and explore the compatibility mechanisms of complex components in SMI
      based on OATPs/oatps. The known effective fractions, the known components in
      Shenmai Formula, and the fractions obtained from SMI by HPLC gradual-separation
      technology were individually/combinedly tested for their effects on OPD uptake in
      rat primary hepatocytes and recombinant OATP1B1/OATP1B3-expressing HEK293T cells.
      The results indicated that the OPD uptake was inhibited by panaxadiol-type
      ginsenosides (ginsenoside Rb1 and Rd), but slightly influenced by panaxatriol
      type ginsenosides in rat primary hepatocytes and recombinant cells. The fractions
      of SMI-3-1 (0-11 min) and SMI-3-3 (15-20 min) obtained by HPLC gradual-separation
      technology were proved to be the major effective fractions that influenced the
      OPD uptake, and subsequently identified as ginsenoside Rb1 and Rd, respectively.
      The plasma concentrations of OPD in rats given OPD+ginsenoside Rb1+ginsenoside Rd
      were higher compared to rats given OPD alone at the same dose. In conclusion,
      ginsenoside Rb1 and Rd are the major effective components in SMI that remarkably
      inhibited the hepatic OPD uptake mediated by OATPs/oatps. The interaction of
      complex components by OATPs/oatps may be one of the important compatibility
      mechanisms in SMI.

PMID- 30186180
TI  - Krukovine Suppresses KRAS-Mutated Lung Cancer Cell Growth and Proliferation by
      Inhibiting the RAF-ERK Pathway and Inactivating AKT Pathway.
AB  - Oncogenic activation of the KRAS gene via point mutations occurs in 20-30% of
      patients with non-small cell lung cancer (NSCLC). The RAS-RAF-ERK and RAS-PI3K
      AKT pathways are the major hyper-activated downstream pathways in RAS mutation,
      which promotes the unlimited lifecycle of cancer cells and their metastasis in
      humans. However, the success of targeted therapy is restricted by many factors.
      Herein, we show a new pharmacological KRAS signaling inhibitor krukovine, which
      is a small molecular bisbenzylisoquinoline alkaloid, isolated from the bark of
      Abuta grandifolia (Mart.) Sandw. (Menispermaceae). This alkaloid targets the KRAS
      downstream signaling pathways in different NSCLC cell lines, such as H460 and
      A549, which are established by KRAS mutations. In the present study, we initially
      investigated the anti-cancer activities of krukovine in KRAS-mutated NSCLC cell
      lines, as well as KRAS wild type cancer cell line and normal lung cell. Results
      indicated that krukovine can inhibit the growth and dose-dependently inhibit the
      colony formation capacity and wound healing ability of H460 and A549. This
      cytotoxic effect is associated with the induction of cell apoptosis and G1 arrest
      in those cell lines. Krukovine treatment also suppressed the C-RAF, ERK, AKT,
      PI3K, p70s6k, and mTOR phosphorylation in H460 and A549. This finding suggests
      that krukovine represses the growth and proliferation of KRAS-mutated cells by
      inactivating AKT signaling pathway and downregulating the RAF-ERK signaling
      pathway. This study provides detailed insights into the novel cytotoxic mechanism
      of an anti-cancer compound from an herbal plant and promotes the anti-cancer
      potential of krukovine in NSCLC with KRAS mutation.

PMID- 30186181
TI  - Emodin Attenuates Lipopolysaccharide-Induced Acute Liver Injury via Inhibiting
      the TLR4 Signaling Pathway in vitro and in vivo.
AB  - Aims: Emodin is an anthraquinone with potential anti-inflammatory properties.
      However, the possible molecular mechanisms and protective effects of emodin are
      not clear. The objective of this study was to investigate the possible molecular
      mechanisms and protective effects of emodin on lipopolysaccharide (LPS)-induced
      acute liver injury (ALI) via the Toll-like receptor 4 (TLR4) signaling pathway in
      the Raw264.7 cell line and in Balb/c mice. Methods: This study established an
      inflammatory cellular model and induced an ALI animal model. TLR4 was
      overexpressed by lentivirus and downregulated by small interfering RNA (siRNA)
      technology. The mRNA and protein levels of TLR4 and downstream molecules were
      detected in cells and liver tissue. The tumor necrosis factor-alpha (TNF-alpha)
      and interleukin (IL)-6 levels in supernatant and serum were determined by ELISA.
      The distribution and expression of mannose receptor C type 1 (CD206) and arginase
      1 (ARG1) in the liver were tested by immunofluorescence. Mouse liver function and
      histopathological observations were assessed. Results: Administration of emodin
      reduced the protein and/or mRNA levels of TLR4 and its downstream molecules
      following LPS challenge in Raw264.7 cells and in an animal model. Additionally,
      emodin suppressed the expression of TNF-alpha and IL-6 in cell culture
      supernatant and serum. The inhibitory effect of emodin was also confirmed in
      RAW264.7 cells, in which TLR4 was overexpressed or knocked down. Additionally,
      ARG1 and CD206 were elevated in the emodin groups. Emodin also decreased serum
      ALT and AST levels and alleviated the liver histopathological damage induced by
      LPS. Conclusion: Emodin showed excellent hepatoprotective effects against LPS
      induced ALI, possibly by inhibiting TLR4 signaling pathways.

PMID- 30186182
TI  - GYY4137 Promotes Mice Feeding Behavior via Arcuate Nucleus Sulfur-Sulfhydrylation
      and AMPK Activation.
AB  - Hydrogen sulfide (H2S) is an endogenous gaseous molecule and plays important
      biological and neurochemical roles in many processes such as the neural activity
      and immunity. The arcuate nucleus (ARC) of hypothalamus is a control center for
      appetite and energy metabolism. AMPK is a gage kinase in the monitoring of energy
      status and regulation of energy metabolism, and it can be activated by H2S via
      CaMKKbeta/AMPK pathway. But the role of H2S in ARC and appetite has not been
      reported. Here we studied the orexigenic effect of H2S and the mechanisms by
      means of GYY4137, a water soluble and slow-releasing donor of H2S, and protein
      sulfur-sulfhydrylation analysis. We demonstrated that GYY4137-derived H2S
      increased food intake of mice, augmented the production of neuropeptide Y (NPY),
      and elevated the protein sulfur-sulfhydrylation level and the activation of AMPK
      and CaMKKbeta in ARC. Blocking sulfur-sulfhydrylation with DTT eliminated GYY4137
      induced activation of AMPK and CaMKKbeta. DTT and preventing AMPK activation in
      ARC with Compound C and Ara-A could both attenuate the orexigenic effect of
      GYY4137. These findings suggest that H2S enhances appetite through protein sulfur
      sulfhydrylation and the activation of AMPK and NPY function in ARC.

PMID- 30186183
TI  - Antidepressant-Like Effects of Cistanche tubulosa Extract on Chronic
      Unpredictable Stress Rats Through Restoration of Gut Microbiota Homeostasis.
AB  - Growing evidence shows that neuropsychiatric disorders, such as depression, are
      linked with gut microbiome through the gut-brain axis. Cistanches Herba is well
      known for the treatment of "kidney-yang" deficiency in traditional Chinese
      medicine (TCM), and has been used for treatment of neurodegenerative diseases in
      recent years. In this study, chronic unpredictable stress (CUS)-induced
      depression model was established to explore the impact of Cistanche tubulosa
      extract (CTE) on behavioral tests, monoamine neurotransmitters and neurotrophic
      factors in hippocampus and colon, gut microbiota composition, and short-chain
      fatty acids (SCFAs) production. Moreover, correlation analysis was used to
      evaluate the functional relationship between altered gut microbiota, changed
      neurotransmitters and neurotrophins in hippocampus and colon, and disturbed
      concentration of SCFAs. CTE significantly improved depression-like behaviors in
      rats under CUS. Brain level of 5-hydroxytryptamine (5-HT) and brain-derived
      neurotrophic factor (BDNF) expression in CUS rats were restored by CTE. The
      relative abundance of gut microbiota and the concentrations of acetate and
      hexanoic acid could also be modulated by CTE treatment. We further showed that
      the application of CTE in CUS rats led to strong correlation among disrupted gut
      microbiota composition, hippocampus neurotransmitter levels, and production of
      neuroactive metabolite SCFAs. Altogether, these results identify CTE as a
      potential treatment for depressive symptoms by restoring homeostasis of gut
      microbiota for microbiota-gut-brain axis disorders, opening new avenues in the
      field of neuropsychopharmacology.

PMID- 30186184
TI  - Inflammasome-Independent NALP3 Contributes to High-Salt Induced Endothelial
      Dysfunction.
AB  - Backgrounds and Aims: Na+ is an important nutrient and its intake, mainly from
      salt (NaCl), is essential for normal physiological function. However, high salt
      intake may lead to vascular injury, independent of a rise in blood pressure (BP).
      Canonical NALP3 inflammasome activation is a caspase-1 medicated process,
      resulting in the secretion of IL-18 and IL-1beta which lead to endothelial
      dysfunction. However, some researches uncovered a direct and inflammasome
      independent role of NALP3 in renal injury. Thus, this study was designed to
      investigate the possible mechanisms of NALP3 in high salt induced endothelial
      dysfunction. Methods and Results: Changes in endothelial function were measured
      by investigating mice (C57BL/6J, NALP3-/- and wild-type, WT) fed with normal salt
      diet (NSD) or high salt diet (HSD) for 12W, and thoracic aortic rings from
      C57BL/6J mice cultured in high-salt medium. Changes of tube formation ability,
      intracellular reactive oxygen species (ROS), and NALP3 inflammasome expression
      were detected using mouse aortic endothelial cells (MAECs) cultured in high-salt
      medium. Consumption of HSD for 12W did not affect BP or body weight in C57BL/6J
      mice. Endothelium-dependent relaxation (EDR) decreased significantly in C57BL/6J
      mice fed with HSD for 12W, and in isolated thoracic aortic rings cultured in high
      salt medium for 24 h. Results from the aortic ring assay also revealed that the
      angiogenic function of thoracic aortas was impaired by either consumption of HSD
      or exposure to high-salt medium. NALP3-/- mice fed with HSD showed a relatively
      mild decrease in EDR function when compared with WT mice. Tube length of thoracic
      aortic rings from NALP3-/- mice was longer than those from WT mice after
      receiving high-salt treatment. Inhibiting NALP3 with a NALP3 antagonist, small
      interfering (si) RNA experiments using si-NALP3, and decomposing ROS
      significantly improved tube formation ability in MAECs under high salt medium.
      NALP3 expression was increased in MAECs cultured with high salt treatment and
      inhibiting NALP3 reversed the down-regulation of p-eNOS induced by high salt in
      MAECs. Conclusion: High salt intake impairs endothelial function, which is at
      least in part mediated by increasing NALP3 expression.

PMID- 30186185
TI  - Non-viral Delivery of Nucleic Acids: Insight Into Mechanisms of Overcoming
      Intracellular Barriers.
AB  - Delivery of genes, including plasmid DNAs, short interfering RNAs (siRNAs), and
      messenger RNAs (mRNAs), using artificial non-viral nanotherapeutics is a
      promising approach in cancer gene therapy. However, multiple physiological
      barriers upon systemic administration remain a key challenge in clinical
      translation of anti-cancer gene therapeutics. Besides extracellular barriers
      including sequestration of gene delivery nanoparticles from the bloodstream by
      resident organ-specific macrophages, and their poor extravasation and tissue
      penetration in tumors, overcoming intracellular barriers is also necessary for
      successful delivery of nucleic acids. Whereas for RNA delivery the endosomal
      barrier holds a key importance, transfer of DNA cargo additionally requires
      translocation into the nucleus. Better understanding of crossing membrane
      barriers by nucleic acid nanoformulations is essential to the improvement of
      current non-viral carriers. This review aims to summarize relevant literature on
      intracellular trafficking of non-viral nanoparticles and determine key factors
      toward surmounting intracellular barriers. Moreover, recent data allowed us to
      propose new interpretations of current hypotheses of endosomal escape mechanisms
      of nucleic acid nanoformulations.

PMID- 30186186
TI  - Can an Integrated Science Approach to Precision Medicine Research Improve Lithium
      Treatment in Bipolar Disorders?
AB  - Clinical practice guidelines identify lithium as a first line treatment for mood
      stabilization and reduction of suicidality in bipolar disorders (BD); however,
      most individuals show sub-optimal response. Identifying biomarkers for lithium
      response could enable personalization of treatment and refine criteria for
      stratification of BD cases into treatment-relevant subgroups. Existing systematic
      reviews identify potential biomarkers of lithium response, but none directly
      address the conceptual issues that need to be addressed to enhance translation of
      research into precision prescribing of lithium. For example, although clinical
      syndrome subtyping of BD has not led to customized individual treatments, we
      emphasize the importance of assessing clinical response phenotypes in biomarker
      research. Also, we highlight the need to give greater consideration to the
      quality of prospective longitudinal monitoring of illness activity and the
      differentiation of non-response from partial or non-adherence with medication. It
      is unlikely that there is a single biomarker for lithium response or
      tolerability, so this review argues that more research should be directed toward
      the exploration of biosignatures. Importantly, we emphasize that an integrative
      science approach may improve the likelihood of discovering the optimal
      combination of clinical factors and multimodal biomarkers (e.g., blood omics,
      neuroimaging, and actigraphy derived-markers). This strategy could uncover a
      valid lithium response phenotype and facilitate development of a composite
      prediction algorithm. Lastly, this narrative review discusses how these
      strategies could improve eligibility criteria for lithium treatment in BD, and
      highlights barriers to translation to clinical practice including the often
      overlooked issue of the cost-effectiveness of introducing biomarker tests in
      psychiatry.

PMID- 30186187
TI  - Safety Challenges of Using High Dose Baclofen for Alcohol Use Disorder: A Focused
      Review.
AB  - Since the early 2000s, the gamma-aminobutyric acid type B (GABA-B) receptor
      agonist baclofen has been extensively used for treating alcohol use disorder
      (AUD). In some countries, like France, Australia, or Germany, baclofen has been
      used at patient-tailored dose regimens, which can reach 300 mgpd or even more in
      some patients. The GABA-B-related pharmacology of baclofen expose patients to a
      specific profile of neuropsychiatric adverse drug reactions (ADRs), primarily
      some frequent sedative symptoms whose risk of occurrence and severity are both
      related to the absolute baclofen dosing and the kinetics of dose variations.
      Other frequent neuropsychiatric ADRs can occur, i.e., tinnitus, insomnia, or
      dizziness. More rarely, other serious ADRs have been reported, like seizures,
      manic symptoms, or sleep apnea. However, real-life AUD patients are also exposed
      to other sedative drugs, like alcohol of course, but also benzodiazepines, other
      drugs of abuse, or other sedative medications. Consequently, the occurrence of
      neuropsychiatric safety issues in these patients is essentially the result of a
      complex multifactorial exposure, in which baclofen causality is rarely obvious by
      itself. As a result, the decision of initiating baclofen, as well as the daily
      dose management should be patient-tailored, according the medical history but
      also the immediate clinical situation of the patient. The overall safety profile
      of baclofen, as well as the clinical context in which baclofen is used, have many
      similarities with the use of opiate substitution medications for opiate use
      disorder. This empirical statement has many implications on how baclofen should
      be managed and dosing should be adjusted. Moreover, this constant patient
      tailored adjustment can be difficult to adapt in the design of clinical trials,
      which may explain inconsistent findings in baclofen-related literature on AUD.

PMID- 30186188
TI  - Prospective Assessment of Daily Patterns of Mood-Related Symptoms.
AB  - Background: The Mood Rhythm Instrument (MRI) is a new self-report questionnaire
      that aims to assess, the presence, and timing of daily patterns of mood-related
      symptoms. Here, we examined the reliability of the MRI against a prospective
      daily investigation over the course of 15 days. As a secondary aim, we examined
      whether the number of items with a perceived daily pattern correlated with
      severity of depressive symptoms and psychological well-being. Methods: Thirty-two
      participants recruited from the general population were asked to prospectively
      fill out a daily version of the MRI (MRI-d) for 15 days. On the 16th day, they
      filled out the MRI, the Beck Depression Inventory (BDI) and the World Health
      Organization 5-item well-being index (WHO-5). Results: The MRI showed high
      agreement with the MRI-d, which suggests that the MRI is a valid tool to assess
      daily patterns of mood symptoms. The number of mood symptoms perceived as having
      daily peaks correlated positively with BDI scores and negatively with WHO-5
      scores. Conclusions: The MRI might be a valid tool to investigate the presence of
      daily patterns and the timing of mood-related factors.The MRI does not seem to be
      influenced by recall or recency biases. Future studies should test the usefulness
      of this new clinical instrument in individuals with mood disorders, as well as
      its ability to detect changes in the daily timing of mood symptoms before and
      after treatment.

PMID- 30186189
TI  - Sense of Coherence and Stress-Related Resilience: Investigating the Mediating and
      Moderating Mechanisms in the Development of Resilience Following Stress or
      Adversity.
AB  - Background: Trauma, stress, and adversity are well-known for having lasting
      negative effects on health. Yet, not all individuals go on to develop
      psychopathology or impaired health. However, little is known about the underlying
      mechanisms which influence the development of stress-related resilience. Sense of
      coherence-revised (SOC-R) may play a role in this process, as it is formed
      through overcoming stress or adversity. It may also influence the steeling
      effect, which suggests that previous exposure to moderate adversity increases
      resilience to later adversities. Objectives: This study aimed to examine the
      mediating and moderating roles of SOC-R in the relationship between stress or
      adversity, and psychological health and well-being. It further aimed to
      investigate the role of SOC-R in steeling processes. Methods: The study used a
      longitudinal design, with data collection at baseline and one-year follow-up.
      Participants included (N = 238) Swiss older adults (Mage = 68.3 years).
      Standardized questionnaires assessed early-life adversity, recent chronic stress,
      SOC-R, and current health and well-being. Mediation and moderation analyses
      examined the mechanisms underpinning stress-related resilience and curvilinear
      associations assessed steeling. Results: Results showed that the Manageability
      subscale of SOC-R significantly moderated the relationship between chronic stress
      and general mental health (b = 0.04, 95% CI [0.007, 0.082], t = 2.32, p < 0.05).
      Furthermore, SOC-R significantly mediated the relationship for general mental
      health (GMH) and satisfaction with life (SWL) with childhood emotional neglect
      (GMH: b = -0.056, 95% BCa CI [-0.126, -0.002]; SWL: b = -0.043, 95% BCa CI [
      0.088, -0.004]), childhood physical neglect (GMH: b = -0.100, 95% BCa CI [-0.232,
      -0.002]; SWL: b = -0.081, 95% BCa CI [-0.181, -0.002]), and chronic stress (GMH:
      b = -0.052, 95% BCa CI [-0.100, -0.001]; SWL: b = -0.055, 95% BCa CI [-0.097, 
      0.020]). No curvilinear associations were observed between stress or adversity
      and SOC-R. Conclusions: This study expands on the limited research on stress
      related resilience by examining the role of SOC-R in the interactions between
      adversity, stress, and health. Future research should examine SOC-R in samples
      with a greater range and different types of adversity. Overall, findings suggest
      that SOC-R is an important mechanism underpinning the development of stress
      related resilience.

PMID- 30186190
TI  - Increased Serum C3 and Decreased UA in Patients of Bipolar Disorder in Chinese
      Han Population.
AB  - The aim of this study is to explore the changes and clinical significance of
      serum C3, C4, hypersensitive C-reactive protein (hsCRP) and uric acid (UA) in
      patients of bipolar disorder (BD). In this case-control study, we recruited 141
      BD patients from The Second Xiangya Hospital, Central South University, and 151
      age and gender matched healthy controls (HC) from the health management central
      of The Second Xiangya Hospital. These patients were divided into two subgroups
      based on medicines use: 91 patients were treated with psychiatric drugs and 50
      patients were drugs free, or four subgroups based on mood states: 54 patients in
      manic/hypomanic phase, 30 patients in depressive phase, 52 patients in euthymic
      phase and 5 patients in mixed phase. Serum levels of C3, C4, hsCRP and UA were
      measured in all subjects. The serum C3 levels in BD patients (0.9981 +/- 0.1849
      g/L) were significantly lower than that in HC group (1.0637 +/- 0.2186 g/L),
      especially the drugs free subgroup and the euthymic subgroup (0.975 +/- 0.153 and
      0.983 +/- 0.182 g/L), while the serum UA levels were significantly higher (354.6
      +/- 90.4 vs. 332.9 +/- 88.7 MUmol/L), especially the drug-treated subgroup and
      manic/hypomanic subgroup (361.56 +/- 93.20 and 376.70 +/- 88.89 MUmol/L), and
      rates of hyperuricaemia (31.91 vs. 17.88%) were significantly higher in BD
      patients than in HC group. The serum C4 and hsCRP levels in HC group showed no
      significant difference with BD patients in whole or those subgroups. These
      findings suggested that the complement and purinergic systems of BD patients
      might be disrupted, the UA levels could be a potential marker in manic phase and
      the C3 might be the marker of therapeutic evaluation of BD patients.

PMID- 30186191
TI  - Collective Emotions: A Case Study of South African Pride, Euphoria and Unity in
      the Context of the 2010 FIFA World Cup.
AB  - Collective emotions experienced as existing objectively and widely shared
      challenge traditional views of emotions based on personal or private interests.
      This paper extends theories of group and crowd emotions focusing on social
      appraisal, social identity, emotional contagion, and ecstatic nationalism, and
      adds an interdisciplinary approach to research on international mega-sporting
      event impacts and legacies by examining the national-level collective emotions
      produced by a mega-sport event-the 2010 World Cup in South Africa. The novel case
      study approach triangulates ethnographic observations of life in downtown
      Johannesburg before and during the World Cup with a critical thematic analysis of
      qualitative interviews of 10 South Africans and the author's and publicly posted
      videorecordings of individual and collective behavior. I explore how citizen
      support for efforts to pursue national projects combined with international
      attention to generate widespread and genuinely coordinated collective emotions of
      euphoria and pride. The social ontology-based analysis considers bottom-up and
      top-down mechanisms of emotional spread and influence along with important
      expressive-performative contributions of culture-specific forms of group-based
      and collective action tendencies. Moreover, the study shows how group agency in
      the form of coordinated ritualistic bases realized group affects spontaneously
      and normatively as South Africans desired, accepted and celebrated achieving team
      and host-related group goals. These results provide new insights into the
      emotions that occur in public events in two phases, (1) creation of collective
      normative commitment in practice related to group ethos and national interests
      and goals prior to the tournament start, and (2) during the tournament when
      dynamic relations between group-based and collective emotions also generated
      feelings of unity and solidarity. Together they highlight unique predisposing
      cultural and historical features of the emotional and affective-discursive
      practices associated with the World Cup for South Africans, limits to the spread
      of emotions of enthusiasm from urban cities to rural areas, forms of excitement
      and celebration in public spaces, instances of ambivalence about efforts to enact
      support for the nation's World Cup team and host role, and indicate how
      collective emotional experiences are internalized, embodied and reproduced in
      accounts of national transformation, concerns about fragile intergroup
      solidarity, and instances of group-based hubristic pride.

PMID- 30186192
TI  - Eye Movement Desensitization and Reprocessing Versus Treatment as Usual in the
      Treatment of Depression: A Randomized-Controlled Trial.
AB  - Eye movement desensitization and reprocessing (EMDR) is a well-established
      treatment for post-traumatic stress disorder. Recent research suggested that it
      may be effective in treating depressive disorders as well. The present study is
      part of a multicenter randomized-controlled trial, the EDEN study, in which a
      homogenous group of 30 patients was treated to test whether EMDR plus treatment
      as usual (TAU) would achieve superior results compared to TAU only in a
      psychosomatic-psychotherapeutic inpatient treatment setting. Both groups were
      assessed by the Beck Depression Inventory-II (BDI-II) and the Global Severity
      Index and depression subscale of the Symptom Checklist 90-Revised. The EMDR + TAU
      group improved significantly better than the TAU group on the BDI-II and Global
      Severity Index, while a marginally significant difference favoring the EMDR + TAU
      group over the TAU group was found on the depression subscale. In the EMDR + TAU
      group, seven out of 14 patients improved below nine points on the BDI-II, which
      is considered to be a full remission, while four out of 16 in the TAU group did
      so. These findings confirm earlier suggestions that EMDR therapy may provide
      additional benefit in the treatment of depression. The present study strengthens
      the previous literature on EMDR therapy in the treatment of depression due to the
      randomized-controlled design of the EDEN study.

PMID- 30186193
TI  - Movement Notation Revisited: Syntax of the Common Morphokinetic Alphabet (CMA)
      System.
AB  - Advances in the study of non-verbal behavior and communication have generated a
      need for movement transcription systems capable of incorporating continuous
      developments in visual and computer technology. Our research team has been
      working on the construction of a common morphokinetic alphabet (CMA) for the
      systematic observation of daily life activities. The project, which was launched
      several years ago, was designed to create a system for describing and analyzing
      body motion expression, physical activity, and physical appearance. In this
      paper, we describe an idiosyncratic application of Noam Chomsky's phrase marker
      grammar to the morphokinetic phrase, the objective being to establish the
      grammatical rules and basic order of the symbol string according to a relational
      tree formed by the breakdown of the syntactic components identified as
      structuring the visual description of movement. Criteria for using the CMA as a
      coding system and a free transcription system are proposed.

PMID- 30186194
TI  - A (Preliminary) Recipe for Obtaining a Testing Effect in Preschool Children: Two
      Critical Ingredients.
AB  - The testing effect refers to the finding that retrieval of previously learned
      information improves retention of that information more than restudy practice
      does. While there is some evidence that the testing effect can already arise in
      preschool children when a particular experimental task is employed, it remains
      unclear whether, for this age group, the effect exists across a wider range of
      tasks. To examine the issue, the present experiments sought to determine the
      potential roles of retrieval-practice and final-test formats, and of immediate
      feedback during retrieval practice for the testing effect in preschoolers.
      Experiments 1 and 2 showed no testing effect in preschoolers when a free-recall
      task was applied during the final test, regardless of whether free recall
      (Experiment 1) or cued recall (Experiment 2) were conducted during retrieval
      practice. In contrast, if cued-recall tasks were used during both retrieval
      practice and the final test (Experiment 3), a reliable testing effect arose.
      Furthermore, the magnitude of the effect was dramatically enhanced when, in
      addition, immediate feedback was provided during retrieval practice (Experiment
      4). The present findings suggest that cued-recall practice and test formats, as
      well as immediate feedback during practice, are crucial ingredients for obtaining
      the testing effect in preschoolers.

PMID- 30186196
TI  - Insights Into the Factors Influencing Student Motivation in Augmented Reality
      Learning Experiences in Vocational Education and Training.
AB  - Research on Augmented Reality (AR) in education has demonstrated that AR
      applications designed with diverse components boost student motivation in
      educational settings. However, most of the research conducted to date, does not
      define exactly what those components are and how these components positively
      affect student motivation. This study, therefore, attempts to identify some of
      the components that positively affect student motivation in mobile AR learning
      experiences to contribute to the design and development of motivational AR
      learning experiences for the Vocational Education and Training (VET) level of
      education. To identify these components, a research model constructed from the
      literature was empirically validated with data obtained from two sources: 35
      students from four VET institutes interacting with an AR application for learning
      for a period of 20 days, and a self-report measure obtained from the
      Instructional Materials Motivation Survey (IMMS). We found that the following
      variables: use of scaffolding, real-time feedback, degree of success, time on
      task and learning outcomes are positively correlated with the four dimensions of
      the ARCS model of motivation: Attention, Relevance, Confidence, and Satisfaction.
      Implications of these results are also described.

PMID- 30186195
TI  - Introducing the General Polytomous Diagnosis Modeling Framework.
AB  - Although considerable developments have been added to the cognitive diagnosis
      modeling literature recently, most have been conducted for dichotomous responses
      only. This research proposes a general cognitive diagnosis model for polytomous
      responses-the general polytomous diagnosis model (GPDM), which combines the G
      DINA modeling process for dichotomous responses with the item-splitting process
      for polytomous responses. The polytomous items are specified similar to
      dichotomous items in the Q-matrix, and the MML estimation is implemented using an
      EM algorithm. Under the general framework, different saturated forms, and some
      reduced forms, can be transformed linearly. Model assessment and adjustment under
      the dichotomous context can be extended to polytomous responses. This simulation
      study demonstrates the effectiveness of the model when comparing the two response
      types. The real-data example further illustrates how the proposed model can make
      a difference in practice.

PMID- 30186197
TI  - Music Preferences and Personality in Brazilians.
AB  - This article analyzes the relationship between musical preference and type of
      personality in a large group of Brazilian young and adult participants (N =
      1050). The study included 25 of 27 states of Brazil and individuals aged between
      16 and 71 years (M = 30.87; SD = 10.50). Of these, 500 were male (47.6%) and 550
      were female (52.4%). A correlational study was carried out applying two online
      questionnaires with quality parameters (content-construct validity and
      reliability), one on musical preference and the other on personality. The results
      indicate four main findings: (1) the musical listening of the participants is
      limited to a reduced number of styles, mainly Pop music and others, typical of
      Brazilian culture; (2) the Brazilian context supposes a determining aspect in the
      low preference of non-Brazilian music; (3) there is a positive correlation
      between most personality types analyzed and the Latin, Brazilian, Classical and
      Ethnic musical styles. A negative correlation between these types of personality
      and the consumption of Rock music was also observed; (4) musical preferences are
      driven not only by personality but in some cases they are also driven by socio
      demographic variables (i.e., age and gender). Likewise, this work shows how
      participants make use of music in personality aspects that may be of interest for
      the analysis of socio-affective behavior (personality) as well as according to
      different socio-demographic variables (e.g., age and gender). More cross-cultural
      research on musical preference and personality would need to be carried out from
      a global perspective, framed in the context of social psychology and studies of
      mass communication.

PMID- 30186198
TI  - Creative Sparks or Paralysis Traps? The Effects of Contradictions on Creative
      Processing and Creative Products.
AB  - Paradoxes are an unavoidable part of work life. The unusualness of attempting to
      simultaneously satisfy contradictory imperatives can result in creative outcomes
      that simultaneously satisfy both imperatives by inducing search for, and
      selection of, novel and useful solutions. Likewise, extant research suggests that
      paradoxes can also result in anxiety, defensiveness, and persistence of old ways
      of doing things. However, there is little work attempting to describe how
      paradoxes affect cognition and when it results in higher or lower creativity. To
      tackle this issue, a theory of paradoxical creativity is developed. Paradoxical
      creativity is the attempt by an individual to creatively resolve a contradiction
      by simultaneously achieving competing demands. The theory is implemented into a
      computational model and a simulation is used to describe how paradoxes affect
      creative cognitive process and how these processes in turn result in higher or
      lower degrees of creativity. The results show that creative output is enhanced
      when paradoxes have a balanced effect on the cognitive processes responsible for
      an individual's capacity to search for new information and willingness to
      tolerate new ideas. Hence, individuals with high baseline levels of creative
      cognition are more likely to suffer negative creative performance consequences
      resulting from contradictory demands. For those individuals, contradictory
      demands may produce more alternatives, which increases uncertainty and time to
      insight (if insight is ever reached). This suggests that incentives or rewards to
      resolve contradictions may have the unintentional effect of reducing creative
      output in some circumstance.

PMID- 30186199
TI  - The Efficiency of Art-Based Interventions in Parental Training.
AB  - In recent years, the field of art therapy has gained momentum, but art therapists
      still tend to work verbally during sessions with parents. The therapeutic
      approach presented here is anchored in the notion that the encounter between the
      art world and treatment creates a unique relationship between therapist, parents
      and the artwork. Eighty-seven parents of five to eight year olds filled in two
      quantitative questionnaires before and after a ten-month therapeutic intervention
      during which their child was treated through art therapy. Two other
      questionnaires were completed by the children and by the 14 art therapists. Three
      groups were tested: (1) Parental training with art-based interventions
      (intervention group). (2) Verbal parental training. (3) No Parental training. The
      parents in the first and second groups met the art therapist for parental
      training once every 3 to 4 weeks. In the intervention group the art intervention
      was based on a uniform protocol of exercises with various materials. It was
      hypothesized that a combination of art-based interventions during parental
      training (parents whose child was receiving art therapy) would contribute more to
      parent-child relationship, affect the parents' self-perceptions of parental
      functioning, and improve the child's daily functioning than verbal parental
      training or no parental training, both in terms of the parents' and the child's
      perception. Analysis of the children's questionnaire indicated significantly
      higher scores in the intervention group than in the control groups for perceived
      cognitive abilities, perceived acceptance by peers and by the mother. Analysis of
      the parents' questionnaires indicated there was no difference in parental
      perceptions of their child, level of satisfaction, or efficiency between the
      intervention and the control groups. The art therapists reported improvement in
      the intervention group on almost every measure. When parents take part in a
      therapeutic experience that enables them to create and play with art materials,
      they may accept and appreciate their inner 'child' more easily. This may help
      them accept the fact that their own children are dependent on them, while at the
      same time acknowledging their need for autonomy, which can heighten children's
      perception of their own acceptance by peers and acceptance by their parents.

PMID- 30186201
TI  - Factorial Validity and Measurement Invariance of the Slovene Version of the
      Cultural Intelligence Scale.
AB  - This study examined the factorial validity of the Slovene version of the cultural
      intelligence scale (CQS) in a representative sample of 1,000 Slovenian
      participants (49% were female). The results of confirmatory factor analysis
      supported the factorial validity of the Slovene CQS and the existence of a
      general (second-order) cultural intelligence factor. The four scales and the
      overall (general) CQS scale showed satisfactory internal consistency. The results
      of multiple-group confirmatory factor analyses supported the hypotheses of
      partial measurement invariance across gender, and full measurement invariance
      across type of settlement (urban vs. rural).

PMID- 30186200
TI  - Exposing an "Intangible" Cognitive Skill Among Collegiate Football Players: II.
      Enhanced Response Impulse Control.
AB  - American football is played in a dynamic environment that places considerable
      demands on a player's ability to make fast, precise reactions while controlling
      premature, impulsive reactions to spatial misinformation. We investigated the
      hypothesis that collegiate football players are more proficient than their non
      athlete counterparts at controlling impulsive motor actions. National Collegiate
      Athletic Association (NCAA) Division I football players (n = 280) and non-athlete
      controls (n = 32) completed a variant of the Simon conflict task, which
      quantifies choice reaction speed and the proficiency of controlling spatially
      driven response impulses. Overall, the choice reaction times (RTs) and accuracy
      rates of football players and controls were equivalent. Similarly, football
      players and controls were equally susceptible to producing incorrect impulsive
      motor responses. However, the slowing of RT attributed to the activation and
      successful inhibition of these impulses (i.e., the Simon effect) was reduced
      significantly among football players compared to controls. Moreover, differences
      in impulse control varied by position among the players, with the reduction being
      greater for offensive than for defensive players. Among offensive players,
      running backs, wide receivers, and offensive linemen had greater impulse control
      than did controls, whereas among defensive players only linebackers had greater
      control. Notably, the Simon effect was reduced by 60% in running backs compared
      to controls. These results contribute to emerging evidence that elite football
      players possess more proficient executive control over their motor systems than
      their age counterparts and suggest that the speed of controlling impulsive motor
      reactions may represent an enhanced cognitive "intangible" among football
      players.

PMID- 30186203
TI  - Internet Users' Valuation of Enhanced Data Protection on Social Media: Which
      Aspects of Privacy Are Worth the Most?
AB  - As the development of the Internet and social media has led to pervasive data
      collection and usage practices, consumers' privacy concerns have increasingly
      grown stronger. While previous research has investigated consumer valuation of
      personal data and privacy, only few studies have investigated valuation of
      different privacy aspects (e.g., third party sharing). Addressing this research
      gap in the literature, the present study explores Internet users' valuations of
      three different privacy aspects on a social networking service (i.e., Facebook),
      which are commonly captured in privacy policies (i.e., data collection, data
      control, and third party sharing). A total of 350 participants will be recruited
      for an experimental online study. The experimental design will consecutively
      contrast a conventional, free-of-charge version of Facebook with four
      hypothetical, privacy-enhanced premium versions of the same service. The privacy
      enhanced premium versions will offer (1) restricted data collection on side of
      the company; (2) enhanced data control for users; and (3) no third party sharing,
      respectively. A fourth premium version offers full protection of all three
      privacy aspects. Participants' valuation of the privacy aspects captured in the
      premium versions will be quantified measuring willingness-to-pay. Additionally, a
      psychological test battery will be employed to examine the psychological
      mechanisms (e.g., privacy concerns, trust, and risk perceptions) underlying the
      valuation of privacy. Overall, this study will offer insights into valuation of
      different privacy aspects, thus providing valuable suggestions for economically
      sustainable privacy enhancements and alternative business models that are
      beneficial to consumers, businesses, practitioners, and policymakers, alike.

PMID- 30186202
TI  - When Intimate Partner Violence Meets Same Sex Couples: A Review of Same Sex
      Intimate Partner Violence.
AB  - Over the past few decades, the causes of and intervention for intimate partner
      violence (IPV) have been approached and studied. This paper presents a narrative
      review on IPV occurring in same sex couples, that is, same sex IPV (SSIPV).
      Despite the myth that IPV is exclusively an issue in heterosexual relationships,
      many studies have revealed the existence of IPV among lesbian and gay couples,
      and its incidence is comparable to (Turell, 2000) or higher than that among
      heterosexual couples (Messinger, 2011; Kelley et al., 2012). While similarities
      between heterosexual and lesbian, gay, and bisexual (LGB) IPV were found, unique
      features and dynamics were present in LGB IPV. Such features are mainly related
      to identification and treatment of SSIPV in the community and to the need of
      taking into consideration the role of sexual minority stressors. Our findings
      show there is a lack of studies that address LGB individuals involved in IPV;
      this is mostly due to the silence that has historically existed around violence
      in the LGB community, a silence built on fears and myths that have obstructed a
      public discussion on the phenomenon. We identified the main themes discussed in
      the published studies that we have reviewed here. The reviews lead us to the
      conclusion that it is essential to create a place where this subject can be
      freely discussed and approached, both by LGB and heterosexual people.

PMID- 30186205
TI  - Are Parents Patient? The Influence of Parenting Role Salience and Parental Status
      on Impatience.
AB  - In the classic intertemporal discounting task (Thaler, 1981), individuals make
      tradeoff decisions between smaller-sooner and larger-later monetary rewards. We
      explored how parental role salience and parental status influences individual's
      choice between smaller-sooner and larger-later choices. Parental role salience is
      manipulated among both parents and non-parents in this research. Our results show
      a significant interaction between parental status and manipulated parental role
      salience. Specifically, we found that parents are more impatient than non
      parents. Additionally, non-parents become more impatient after parental role
      salience manipulation, similar to parents. Theoretical implications of our
      findings are discussed.

PMID- 30186204
TI  - Inhibitory Pathways for Processing the Temporal Structure of Sensory Signals in
      the Insect Brain.
AB  - Insects have acquired excellent sensory information processing abilities in the
      process of evolution. In addition, insects have developed communication schemes
      based on the temporal patterns of specific sensory signals. For instance, male
      moths approach a female by detecting the spatiotemporal pattern of a pheromone
      plume released by the female. Male crickets attract a conspecific female as a
      mating partner using calling songs with species-specific temporal patterns. The
      dance communication of honeybees relies on a unique temporal pattern of vibration
      caused by wingbeats during the dance. Underlying these behaviors, neural circuits
      involving inhibitory connections play a critical common role in processing the
      exact timing of the signals in the primary sensory centers of the brain. Here, we
      discuss common mechanisms for processing the temporal patterns of sensory signals
      in the insect brain.

PMID- 30186206
TI  - Large-Group One-Session Treatment: A Feasibility Study of Exposure Combined With
      Applied Tension or Diaphragmatic Breathing in Highly Blood-Injury-Injection
      Fearful Individuals.
AB  - Objective: Large-group one-session treatments (LG-OSTs) might represent a
      promising treatment tool as increasing evidence suggests their effectiveness in
      individuals with different situational fears. In the present study, we explored
      feasibility and effectiveness of an exposure-based LG-OST protocol applying
      applied tension and diaphragmatic breathing as coping strategies in a sample of
      40 individuals, highly fearful of blood-injury-injection (BII). Method: We
      assessed participants' BII-fear using questionnaires and a behavioral approach
      test (BAT) before and after treatment, consisting of a blood-drawing procedure.
      Stability of treatment effects was assessed via online-survey at 7-month follow
      up. Results: The LG-OST procedure evidenced feasible and effective. Pre-post
      treatment comparisons showed medium to large treatment effects (d = 0.40-0.93)
      regarding the questionnaire measures. After being treated, 70% of the individuals
      successfully underwent a blood drawing. Moreover, participants continued to
      improve in the post follow-up interval leading to large treatment effects (d =
      1.19-1.62). Conclusion: In treating BII-fear, LG-OSTs might not only serve within
      a framework of a stepped care approach but also could represent a useful single
      treatment option. Additionally, due to their high efficiency and standardization
      of treatment delivery, LG-OST protocols might foster research at the interface of
      basic and clinical research.

PMID- 30186207
TI  - Factors Influencing High School Students' Interest in pSTEM.
AB  - The transition from high school to college is an important choice point for the
      pursuit of physical science, technology, engineering, and mathematics (pSTEM)
      career paths, with students in the United States switching from course selection
      that is proscribed by state graduation requirements in high school to choosing
      classes and paths of study more freely in college. Here two studies examine
      whether social factors identified to inhibit interest in pSTEM within college
      students similarly affect high school students, and in particular whether these
      factors could contribute to gender differences in interest in pursuing pSTEM. We
      find a lower sense of social and ability belonging and lower self-efficacy among
      female than male high school students pursuing pSTEM classes. In addition, for
      females but not males, social belonging significantly predicts intentions to
      continue to pursue pSTEM, highlighting the importance of considering whether low
      social belonging inhibits intentions to pursue pSTEM for female but not male
      students. We also find that perceptions of pSTEM fields as requiring innate
      brilliance more than hard work selectively discourage female students from
      intending to further pursue pSTEM. Together the studies highlight the potential
      impact of both subjective self-perceptions and perceptions about pSTEM fields on
      students' interest in pSTEM and further identify processes that may selectively
      dissuade high school females from pursuing pSTEM career paths relative to males.

PMID- 30186208
TI  - Cooperative Team Learning and the Development of Social Skills in Higher
      Education: The Variables Involved.
AB  - The cooperative methodology provides an opportunity for university students to
      develop interpersonal, social, and teamwork competences which can be decisive in
      their professional and social success. The research described here examines the
      influence of cooperative learning on the social skills necessary for teamwork.
      Furthermore, it analyses whether the continued use of this type of learning, the
      type of group, the basic social skills for teamwork, or the academic level of the
      students, influence their efficacy. To do so, we have designed a research project
      of a quasi-experimental kind with a pre-test, a post-test, and a control group,
      in which 346 university undergraduate students studying degrees in Infant and
      Primary Education completed self-report surveys about behavior patterns in social
      skills concerning self-assertion and the reception and imparting of information
      in teamwork situations. The results show that cooperative learning in university
      classrooms is effective as a method for developing the social skills necessary
      for teamwork, as well as the relevance of the control over the number of students
      in a group, the basic social skills, or the academic level of the students, as
      relevant factors related with efficacy; where continuity over time in the use of
      the cooperative methodology is what marks the greatest differences in the
      development of the social skills necessary for teamwork. It is important to
      stress that when students are asked to work autonomously in teams, with the aim
      of favoring the development of social skills, they should be given adequate
      structures that can guarantee the minimum conditions of participation, so as to
      allow a proper development of the said social skills.

PMID- 30186209
TI  - The Modality-Specific Learning Style Hypothesis: A Mini-Review.
AB  - The impact on learning outcome of tailoring instruction and teaching toward
      modality-specific learning style preferences has been researched and debated for
      decades. Several topical reviews have concluded that there is no evidence to
      support the meshing hypothesis and that it represents a persistent neuromyth in
      education. The concept, however, is still utilized in educational practice and
      favored by many academics. This mini-review presents literature, which has
      applied explicit and rigorous methodological criteria, in relation to the meshing
      hypothesis. In order to demonstrate evidence for the meshing hypothesis, studies
      had to screen participants for their preferred learning style, assign
      participants to matched or non-matched conditions, and then provide the same test
      to assess learning for all participants, as well as presenting statistical
      crossover-interaction effects. Across studies that have applied these
      methodological criteria, the overall effect sizes were very low and non
      significant, indicating that there is still no replicable statistical evidence
      for enhanced learning outcome by aligning instruction to modality-specific
      learning styles.

PMID- 30186210
TI  - The Experience of Beauty of Chinese Poetry and Its Neural Substrates.
AB  - Chinese poetry has a long history and high esthetic value. People who engage
      esthetically with Chinese poetry would feel the sense of beauty naturally.
      However, there is little information regarding what happens in the brain when an
      individual appreciates Chinese poetry, and how the brain processes the subject's
      appreciation of beauty. Herein, we used functional magnetic resonance imaging
      (fMRI) to investigate the neural substrates of experiencing beauty by
      appreciating Chinese poetry. The participants in our study were 28 college
      students and the stimuli consisted of 25 Chinese poetry and 25 prose selections.
      Based on an event-related paradigm, the findings of this study suggested that
      different areas scattered in both the left and right cerebral hemispheres are
      activated when an individual appreciates Chinese poetry. Compared to reading
      prose, appreciating Chinese poetry heightens the activation of the left inferior
      orbitofrontal cortex (OFC), the bilateral insula, the left fusiform, the left
      supplementary motor area (SMA), and the left precentral gyrus. In these areas,
      the left inferior OFC and the bilateral insula are considered closely related to
      experiencing beauty of Chinese poetry, which have been demonstrated that it is an
      important neural basis of esthetic beauty when using other types of materials.
      The findings of this study shed new light on the complex but ordinary processes
      of experiencing beauty when appreciating Chinese poetry and show that some key
      processes underlying the feeling of esthetic beauty are shared across different
      esthetic domains.

PMID- 30186211
TI  - The Difference in Perceptual Anticipation Between Professional Tennis Athletes
      and Second-Grade Athletes Before Batting.
AB  - To investigate the differences in cognitive processing of perceptual anticipation
      of tennis players at different levels before batting by the event-related
      potential (ERP) technique, we used the skilled-expert paradigm. We compared the
      cognitive and neural mechanisms of professional tennis athletes and second-grade
      athletes relating to their perceptual anticipation of the batting line at
      different time points [the time point of the ball landing (T0), and the 80 ms
      before batting time point (T1)]. The results showed that, regardless of the T0 or
      T1 time point, professional tennis athletes had shorter anticipation times and
      higher correct batting line rates than second-grade athletes. The ERP results
      demonstrated that compared with second-grade athletes, professional tennis
      athletes induced smaller N1 amplitudes and larger P2 amplitudes in early
      perceptual anticipation, and induced smaller N2 and larger P3 amplitudes in late
      perceptual anticipation. These studies suggest that, regardless of whether they
      are in an early or late stage, tennis professional athletes are faster and more
      accurate in respect of their perceptual anticipation of tennis lines than second
      grade athletes are. This is possible since the relevant neural network of the
      former is more easily activated and faster. The prefrontal cortex may be a
      critical area of the brain for perceptual anticipation in tennis.

PMID- 30186213
TI  - Predicting Fluency With Language Proficiency, Working Memory, and Directionality
      in Simultaneous Interpreting.
AB  - Simultaneous interpreting (SI) is a complex bilingual verbal activity that poses
      great challenges for working memory (WM) and language proficiency. Fluency is one
      of the crucial indicators in evaluating SI quality, the violation of which is
      characterized by disfluency indicators such as interruptions, hesitations,
      repetitions, corrections, and blanks. To uncover factors underlying fluency in
      SI, 22 interpreting students performed a battery of tasks to test their language
      proficiency and WM. Two SI tasks, both from Chinese to English and from English
      to Chinese, were also conducted, and fluency was evaluated according to the five
      indicators. Two factors (language proficiency and WM) and the five objectively
      measured disfluency indicators were then used as input for a regression analysis
      in both directions to model factors underlying fluency in SI performance. The
      results reveal that, with fluency measured as a whole, WM and directionality
      yield a significant effect on fluency, and that WM is the only variable that
      predicts fluency in both directions, accounting for 50 and 51% of the variation
      in the occurrence of disfluencies in Chinese-English and English-Chinese
      interpreting, respectively. The findings clarify for the first time the role of
      language proficiency, WM, and directionality upon fluency in SI, indicating the
      critical role of WM capability as compared with language skills in fluent
      production. The research also supports the position that, for interpreting
      students, interpreting performance tends to be more fluent in the non-native to
      native language direction.

PMID- 30186212
TI  - Induced Negative Mood Increases Dictator Game Giving.
AB  - The study examines the influence of induced negative mood on dictator game giving
      (DGG) with two recipients. Participants (N = 63) played the role of a dictator in
      a three-player dictator game. They could choose among two options: an altruistic
      option, where two receivers receive 10 Euros and the dictator himself receives
      nothing, or a selfish option, where the dictator himself receives 5 Euros and
      both receivers receive nothing. For half of the participants, the second option
      entailed that only one receiver receives nothing and the other receives 10 Euros.
      After four rounds, participants were randomly assigned to look at 10 pictures
      with either positive or negative emotional content with the purpose of inducing
      positive or negative mood. The results show that looking at pictures with
      negative emotional content increases anxiety and skin conductance and increases
      DGG in the remaining four rounds of the game. On the other hand, whether the
      selfish option would imply that one or both recipients receive nothing does not
      seem to have a strong influence on DGG. PsycINFO Classification code: 2340; 2360.

PMID- 30186214
TI  - Face-to-Face and Distance Education Modalities in the Training of Healthcare
      Professionals: A Quasi-Experimental Study.
AB  - This study evaluates the effectiveness of an 18-month-long course in Family
      Health. The course was offered in two modalities, distance education and face-to
      face learning. Dependent variables were as follows: self-regulation of learning,
      procrastination, the perception of self-efficacy, and academic performance. The
      course was attended by 27 health professionals (i.e., physicians, nurses, and
      dentists) working in the Brazilian Unified Health System. The investigation
      followed a quasi-experimental design. Participants in the two modalities achieved
      similar academic performance; and globally no statistically significant
      differences were found regarding the study variables. Findings, notwithstanding
      their importance for professional training in health, are preliminary and further
      research is needed on the effectiveness of training modalities distance education
      and face-to-face learning (e.g., focus groups, interviews, online monitoring).
      The educational implications of this study are discussed and analyzed considering
      specificities and differences of each modality.

PMID- 30186215
TI  - Mechanism of the SNARC Effect in Numerical Magnitude, Time Sequence, and Spatial
      Sequence Tasks: Involvement of LTM and WM.
AB  - The spatial-numerical association of response codes (SNARC) effect refers to the
      phenomenon that responses involving small numbers are faster with the left hand
      and responses involving large numbers are faster with the right hand. Previous
      studies have investigated the mechanism of the SNARC effect only when the time
      sequence is induced by centrally presented successive numbers. No study has
      investigated the mechanism of the SNARC effect when the spatial sequence is
      induced. Given that the induction of a spatial sequence together with a time
      sequence provides a new temporary reference for the serial order to be coded in
      working memory (WM), it would be interesting to examine the SNARC effect when
      both the time sequence and spatial sequence are induced. Therefore, a novel
      priming paradigm that simultaneously induced the time sequence and spatial
      sequence was employed in the present study to investigate the mechanism of the
      SNARC effect. Specifically, the time sequence and spatial sequence were induced
      by presenting a series of self-paced successive numbers, centrally or in a left
      to-right or right-to-left direction, on the screen. Following the presentation of
      successive numbers, the probe number was centrally presented on the screen and
      university students were asked to distinguish to which time sequence or spatial
      sequence the probe number belonged by pressing a specified key of a qwerty
      keyboard. The results indicated that (1) the SNARC effect simultaneously appeared
      in the processing of the number magnitude and time sequence when only the time
      sequence was induced. (2) The SNARC effect disappeared in the processing of the
      time sequence; however, the SNARC effect coexisted in the processing of the
      numerical magnitude and spatial sequence when the spatial sequence was induced
      and participants performed a time sequence relevant task. (3) The SNARC effect
      coexisted in the processing of the numerical magnitude, time sequence, and
      spatial sequence when the spatial sequence was induced and participants performed
      a spatial sequence relevant task. Based on these results, we conclude that
      whether the SNARC effect coexists in the processing of the numerical magnitude,
      the time sequence and spatial sequence were influenced by the spatial sequence
      and relevant task. The results further support the mental whiteboard hypothesis
      and extended the WM account. Implications for theories on the SNARC effect were
      discussed.

PMID- 30186216
TI  - Is Diffusion Tensor Imaging a Good Biomarker for Early Parkinson's Disease?
AB  - Objectives: To assess white matter abnormalities in Parkinson's disease (PD).
      Methods: A hundred and thirty-two patients with PD (mean age 60.93 years; average
      disease duration 7.8 years) and 137 healthy controls (HC; mean age 57.8 years)
      underwent the same MRI protocol. Patients were assessed by clinical scales and a
      complete neurological evaluation. We performed a TBSS analysis to compare
      patients and controls, and we divided patients into early PD, moderate PD, and
      severe PD and performed an ROI analysis using tractography. Results: With TBSS we
      found lower FA in patients in corpus callosum, internal and external capsule,
      corona radiata, thalamic radiation, sagittal stratum, cingulum and superior
      longitudinal fasciculus. Increased AD was found in the corpus callosum, fornix,
      corticospinal tract, superior cerebellar peduncle, cerebral peduncle, internal
      and external capsules, corona radiata, thalamic radiation and sagittal stratum
      and increased RD were seen in the corpus callosum, internal and external
      capsules, corona radiata, sagittal stratum, fornix, and cingulum. Regarding the
      ROIs, a GLM analysis showed abnormalities in all tracts, mainly in the severe
      group, when compared to HC, mild PD and moderate PD. Conclusions: Since major
      abnormalities were found in the severe PD group, we believe DTI analysis might
      not be the best tool to assess early alterations in PD, and probably, functional
      and other structural analysis might suit this purpose better. However it can be
      used to differentiate disease stages, and as a surrogate marker to assess disease
      progression, being an important measure that could be used in clinical trials.
      HIGHLIGHTS DTI is not the best tool to identify early PDDTI can differentiate
      disease stagesDTI analysis may be a useful marker for disease progression.

PMID- 30186218
TI  - Optimization of an Anti-NMDA Receptor Autoantibody Diagnostic Bioassay.
AB  - Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is one of the most
      frequently encountered autoimmune encephalitis. The pathogenesis of both anti
      NMDAR encephalitis and schizophrenia involve down-regulation of NMDA receptors.
      Whether autoantibody-mediated destruction of neuronal NMDA receptors is
      associated with schizophrenia or first-episode psychosis (FEP) remains unclear,
      as the current findings from different groups are inconsistent. The main culprits
      are likely due to heterogeneity of autoantibodies (autoAbs) in a patient's blood
      or cerebrospinal fluid (CSF), as well as due to limitation of the current
      detection methods for anti-NMDAR autoAbs. Here, we optimized the current
      diagnostic method based on the only commercially-available anti-NMDAR test kit.
      We first increased detection sensitivity by replacing reporter fluorophore
      fluorescein isothiocyanate (FITC) in the kit with Alexa Fluor 488, which is
      superior in resisting photobleaching. We also found that using an advanced
      imaging system could increase the detection limit, compared to using a simple
      fluorescence microscope. To improve test accuracy, we implemented secondary
      labeling with a well-characterized mouse anti-NR1 monoclonal antibody (mAb) after
      immunostaining with a patient's sample. The degree of colocalization between
      mouse and human antisera in NMDAR-expressing cells served to validate test
      results to be truly anti-NMDAR positive or false-positive. We also incorporated
      DNA-specific DAPI to simultaneously differentiate autoAbs targeting the plasma
      membrane from those targeting cell nuclei or perinuclear compartments. All the
      technical implementation could be integrated in a general hospital laboratory
      setting, without the need of specialized expertise or equipment. By sharing our
      experience, we hope this may help improve sensitivity and accuracy of the
      mainstream method for anti-NMDAR detection.

PMID- 30186217
TI  - Current Progress in CNS Imaging of Myotonic Dystrophy.
AB  - Neuroimaging in myotonic dystrophies provided a major contribution to the insight
      into brain involvement which is highly prevalent in these multisystemic
      disorders. Particular in Myotonic Dystrophy Type 1, conventional MRI first
      revealed hyperintense white matter lesions, predominantly localized in the
      anterior temporal lobe. Brain atrophy and ventricle enlargement were additional
      early findings already described almost 30 years ago. Since then, more advanced
      and sophisticated imaging methods have been applied in Myotonic Dystrophy Types 1
      and 2. Involvement of actually normal appearing white matter and widespread
      cortical affection in PET studies were key results toward the recognition of
      diffuse and not only focally localized brain pathology in vivo. Later, structural
      abnormalities of both, gray and white matter, have been found in both forms of
      the disorder, albeit more prominent in myotonic dystrophy type 1. In Type 1, a
      consistent widespread cortical and subcortical involvement of gray and white
      matter affecting all lobes, brainstem and cerebellum was observed. Spectroscopy
      studies gave additional evidence of neuronal and glial damage in both types.
      Central questions regarding the origin and spatiotemporal evolution of the CNS
      involvement and its relevance for clinical symptoms had already been raised 30
      years ago, however are still not answered. Results of correlation analyses
      between neuroimaging and clinical parameters are diverse and with few exceptions
      not well reproducible across studies. It may be related to the fact that most of
      the reported studies included only small numbers of subjects, sometimes even not
      separating Myotonic Dystrophy Type 1 from Type 2. But this heterogeneity may also
      support the current point of view that the clinical impairments are not simply
      linked to specific and regionally circumscribed structural or functional brain
      alterations. It seems more convincing that disturbed networks build the
      functional and structural substrate of clinical symptoms in these disorders as it
      is proposed in other neuropsychiatric diseases. Consecutively, structural and
      functional network analyses may provide additional information regarding the link
      between brain pathology and clinical symptoms. Up to now, only cross-sectional
      neuroimaging studies have been published. To analyze the temporal evolution of
      brain affection, longitudinal studies are urgently needed, and systematic natural
      history data would be useful to identify potential biomarkers for therapeutic
      studies.

PMID- 30186219
TI  - Endovascular Treatment of Intracranial Atherosclerotic Stenosis: Current Debates
      and Future Prospects.
AB  - Intracranial atherosclerotic stenosis (ICAS) is a common cause of transient
      ischemic attack (TIA) and ischemic stroke. Endovascular treatment, including
      balloon angioplasty alone, balloon-mounted stents, and self-expandable stent
      placement with or without prior angioplasty, is an alternative to medical
      treatment for the prevention of recurrent TIA or ischemic stroke in patients with
      ICAS. Although the SAMMPRIS and VISSIT trials supported medical management alone
      against endovascular treatments, both randomized controlled trials (RCT) were
      criticized due to flaws relating to patient-, intervention-, and operator-related
      factors. In this review, we discuss the current debate regarding these aspects
      and suggest approaches to solve current controversies in the future. In our
      opinion, endovascular treatment in carefully selected patients, individualized
      choice of endovascular treatment subtypes, and an experienced multidisciplinary
      team managing the patient in the pre-, peri- and post-procedural period have the
      potential to provide safe and efficious treatment of patients with symptomatic
      ICAS.

PMID- 30186220
TI  - Longitudinal Bedside Assessments of Brain Networks in Disorders of Consciousness:
      Case Reports From the Field.
AB  - Clinicians are regularly faced with the difficult challenge of diagnosing
      consciousness after severe brain injury. As such, as many as 40% of minimally
      conscious patients who demonstrate fluctuations in arousal and awareness are
      known to be misdiagnosed as unresponsive/vegetative based on clinical consensus.
      Further, a significant minority of patients show evidence of hidden awareness not
      evident in their behavior. Despite this, clinical assessments of behavior are
      commonly used as bedside indicators of consciousness. Recent advances in
      functional high-density electroencephalography (hdEEG) have indicated that
      specific patterns of resting brain connectivity measured at the bedside are
      strongly correlated with the re-emergence of consciousness after brain injury. We
      report case studies of four patients with traumatic brain injury who underwent
      regular assessments of hdEEG connectivity and Coma Recovery Scale-Revised (CRS-R)
      at the bedside, as part of an ongoing longitudinal study. The first, a patient in
      an unresponsive wakefulness state (UWS), progressed to a minimally-conscious
      state several years after injury. HdEEG measures of alpha network centrality in
      this patient tracked this behavioral improvement. The second patient, contrasted
      with patient 1, presented with a persistent UWS diagnosis that paralleled with
      stability on the same alpha network centrality measure. Patient 3, diagnosed as
      minimally conscious minus (MCS-), demonstrated a significant late increase in
      behavioral awareness to minimally conscious plus (MCS+). This patient's hdEEG
      connectivity across the previous 18 months showed a trajectory consistent with
      this increase alongside a decrease in delta power. Patient 4 contrasted with
      patient 3, with a persistent MCS- diagnosis that was similarly tracked by
      consistently high delta power over time. Across these contrasting cases, hdEEG
      connectivity captures both stability and recovery of behavioral trajectories both
      within and between patients. Our preliminary findings highlight the feasibility
      of bedside hdEEG assessments in the rehabilitation context and suggest that they
      can complement clinical evaluation with portable, accurate and timely generation
      of brain-based patient profiles. Further, such hdEEG assessments could be used to
      estimate the potential utility of complementary neuroimaging assessments, and to
      evaluate the efficacy of interventions.

PMID- 30186221
TI  - Optimal Delay Time of CT Perfusion for Predicting Cerebral Parenchymal Hematoma
      After Intra-Arterial tPA Treatment.
AB  - Background and Purpose: Cerebral hemorrhage is a serious potential complication
      of stroke revascularization, especially in patients receiving intra-arterial
      tissue-type plasminogen activator (tPA) therapy. We investigated the optimal pre
      intervention delay time (DT) of computed tomography perfusion (CTP) measurement
      to predict cerebral parenchymal hematoma (PH) in acute ischemic stroke (AIS)
      patients after intra-arterial tissue plasminogen activator (tPA) treatment.
      Methods: The study population consisted of a series of patients with AIS who
      received intra-arterial tPA treatment and had CTP and follow-up computed
      tomography/magnetic resonance imaging (CT/MRI) to identify hemorrhagic
      transformation. The association of increasing DT thresholds (>2, >4, >6, >8, and
      >10 s) with PH was examined using receiver operating characteristic (ROC)
      analysis and logistic regression. Results: Of 94 patients, 23 developed PH on
      follow-up imaging. Receiver operating characteristic analysis revealed that the
      greatest area under the curve for predicting PH occurred at DT > 4 s (area under
      the curve, 0.66). At this threshold of > 4 s, DT lesion volume >= 30.85 mL
      optimally predicted PH with 70% sensitivity and 59% specificity. DT > 4 s volume
      was independently predictive of PH in a multivariate logistic regression model (P
      < 0.05). Conclusions: DT > 4 s was the parameter most strongly associated with
      PH. The volume of moderate, not severe, hypo-perfusion on DT is more strongly
      associated and may allow better prediction of PH after intra-arterial tPA
      thrombolysis.

PMID- 30186223
TI  - Balance Changes in Patients With Relapsing-Remitting Multiple Sclerosis: A Pilot
      Study Comparing the Dynamics of the Relapse and Remitting Phases.
AB  - Aims: To compare balance changes over time during the relapse phase of relapsing
      remitting multiple sclerosis (RRMS) with balance control during the remitting
      phase. Methods: Balance control during stance and gait tasks of 24 remitting
      phase patients (mean age 43.7 +/- 10.5, 15 women, mean EDSS at baseline 2.45 +/-
      1.01) was examined every 3 months over 9 months and compared to that of nine
      relapsing patients (age 42.0 +/- 12.7, all women, mean EDSS at relapse onset 3.11
      +/- 0.96) examined at relapse onset and 3 months later. Balance was also compared
      to that of 40 healthy controls (HCs) (age 39.7 +/- 12.6, 25 women). Balance
      control was measured as lower-trunk sway angles with body-worn gyroscopes.
      Expanded Disability Status Scale scores (EDSS) were used to monitor, clinically,
      disease progression. Results: Remitting-phase patients showed more unstable
      stance balance control than HCs (p < 0.04) with no worsening over the observation
      period of 9 months. Gait balance control was normal (p > 0.06). Relapsing
      patients had stance balance control significantly worse at onset compared to
      remitting-phase patients and HCs (p < 0.04). Gait tasks showed a significant
      decrease of gait speed and trunk sway in relapsing patients (p = 0.018)
      compatible with having increased gait instability at normal speeds. Improvement
      to levels of remitting patients generally took longer than 3 months. Balance and
      EDSS scores were correlated for remitting but not for relapse patients.
      Conclusions: Balance in remitting RRMS patients does not change significantly
      over 9 months and correlated well with EDSS scores. Our results indicate that
      balance control is a useful measure to assess recovery after a relapse,
      particularly in patients with unchanged EDSS scores. Based on our results,
      balance could be considered as additional measurement to assess recovery after a
      relapse, particularly in patients with unchanged EDSS.

PMID- 30186222
TI  - Epidemiological Features of Spinal Cord Injury in China: A Systematic Review.
AB  - Background: Spinal cord injury (SCI) is a severe condition that disrupts
      patients' physiological, mental, and social well-being state and exerts great
      financial burden on patients, their families and social healthcare system. This
      review intends to compile studies regarding epidemiological features of SCI in
      China. Methods: Searches were conducted on PubMed, EMBASE, Web of Science and
      Cochrane Library for relevant studies published through January, 2018. Studies
      reported methodological and epidemiological data were collected by two authors
      independently. Results: Seventeen studies met the inclusion criteria. Two studies
      reported incidence of SCI that is 60.6 in Beijing (2002) and 23.7 in Tianjin
      (2004-2008). All studies showed male had a larger percentage in SCI compared to
      female except Taiwan (2000-2003). The average male and female ratio was 3-4:1 in
      China and the highest male and female ratio was 5.74: 1 in Tianjin (2004-2007).
      Farmers, laborers and unemployed people accounted for more than half of the SCI
      patients in China. Fall was the primary causation with exception of Heilongjiang
      (2009-2013), Beijing (2001-2010), and Taiwan (2002-2003), where motor vehicle
      collision (MCVs) was the leading causation. Pulmonary infection, urinary tract
      infection and bedsore were common complications, accounting for approximately 70%
      of SCI patients in China. Conclusion: This review shows that epidemiological
      features of SCI are various in different regions in China and prevention should
      be implemented by regions. The number of patients with SCI result from fall and
      MCVs may become a main public health problem because population aging and
      economic developing in China. However, because all included studies were
      retrospective and lacking a register system in China, some data were incomplete
      and some cases may be left out, so the conclusion may not be generalizable to the
      other regions.

PMID- 30186224
TI  - Application of Machine Learning to Automated Analysis of Cerebral Edema in Large
      Cohorts of Ischemic Stroke Patients.
AB  - Cerebral edema contributes to neurological deterioration and death after
      hemispheric stroke but there remains no effective means of preventing or
      accurately predicting its occurrence. Big data approaches may provide insights
      into the biologic variability and genetic contributions to severity and time
      course of cerebral edema. These methods require quantitative analyses of edema
      severity across large cohorts of stroke patients. We have proposed that changes
      in cerebrospinal fluid (CSF) volume over time may represent a sensitive and
      dynamic marker of edema progression that can be measured from routinely available
      CT scans. To facilitate and scale up such approaches we have created a machine
      learning algorithm capable of segmenting and measuring CSF volume from serial CT
      scans of stroke patients. We now present results of our preliminary processing
      pipeline that was able to efficiently extract CSF volumetrics from an initial
      cohort of 155 subjects enrolled in a prospective longitudinal stroke study. We
      demonstrate a high degree of reproducibility in total cranial volume registration
      between scans (R = 0.982) as well as a strong correlation of baseline CSF volume
      and patient age (as a surrogate of brain atrophy, R = 0.725). Reduction in CSF
      volume from baseline to final CT was correlated with infarct volume (R = 0.715)
      and degree of midline shift (quadratic model, p < 2.2 * 10-16). We utilized
      generalized estimating equations (GEE) to model CSF volumes over time (using
      linear and quadratic terms), adjusting for age. This model demonstrated that CSF
      volume decreases over time (p < 2.2 * 10-13) and is lower in those with cerebral
      edema (p = 0.0004). We are now fully automating this pipeline to allow rapid
      analysis of even larger cohorts of stroke patients from multiple sites using an
      XNAT (eXtensible Neuroimaging Archive Toolkit) platform. Data on kinetics of
      edema across thousands of patients will facilitate precision approaches to
      prediction of malignant edema as well as modeling of variability and further
      understanding of genetic variants that influence edema severity.

PMID- 30186226
TI  - SLC6A3 Polymorphism Predisposes to Dopamine Overdose in Parkinson's Disease.
AB  - In Parkinson's disease (PD), cognitive functions mediated by brain regions
      innervated by ventral tegmental area (VTA) worsen with dopamine replacement
      therapy, whereas processes relying on regions innervated by the substantia nigra
      pars compacta (SNc) improve. The SLC6A3 gene encodes the dopamine transporter
      (DAT). The common 9R polymorphism produces higher DAT concentrations and
      consequently lower baseline dopamine than SLC6A3 wildtype. Whether SLC6A3
      genotype modulates the effect of dopaminergic therapy on cognition in PD is not
      known. We investigated the effect of dopaminergic therapy and SLC6A3 genotype on
      encoding and recall of abstract images using the Aggie Figures Learning Test in
      PD patients. Encoding depends upon brain regions innervated by the VTA, whereas
      recall is mediated by widespread brain regions, a number innervated by the SNc.
      We found that dopaminergic therapy worsened encoding of abstract images in 9R
      carriers only. In contrast, dopaminergic therapy improved recall of abstract
      images in all PD patients, irrespective of SLC6A3 genotype. Our findings suggest
      that 9R-carrier PD patients are more predisposed to dopamine overdose and
      medication-induced impairment of cognitive functions mediated by VTA-innervated
      brain regions. Interestingly, PD patients without the 9R polymorphism did not
      show such an impairment. SLC6A3 genotype does not modulate the dopaminergic
      therapy-induced improvement of functions mediated by SNc-innervated regions in PD
      patients.

PMID- 30186227
TI  - Low Diagnostic Yield of Routine Cerebrospinal Fluid Analysis in Juvenile Stroke.
AB  - Background: The diagnostic value of cerebrospinal fluid (CSF) analysis in
      juvenile stroke, i.e., stroke in young adult patients, is not well studied. We
      sought to determine the therapeutic impact of routine CSF-analysis in young
      adults with acute ischemic stroke or transient ischemic attack (TIA). Methods: We
      abstracted data from patients with acute cerebral ischemia aged 18-45 years who
      were consecutively admitted to our stroke center between 01/2008 and 12/2015. We
      routinely performed CSF-analysis in patients with hitherto unknown stroke
      etiology after complete diagnostic work up. We assessed the frequency and
      underlying causes of abnormal CSF-findings and their impact on secondary stroke
      prevention therapy. Results: Among 379 patients (median [IQR:IQR3-IQR1] age 39
      [10:43-33] years, 48% female) with acute ischemic stroke (n = 306) or TIA (n =
      73), CSF analysis was performed in 201 patients (53%). Of these, 25 patients
      (12.4 %) had CSF pleocytosis (leucocyte cell count >= 5 Mpt/L), that was rated as
      non-specific (e.g., traumatic lumbar puncture, reactive pleocytosis) in 22
      patients. Only 3 patients (1.5% of all patients who underwent CSF-analysis) with
      CSF-pleocytosis had specific CSF-findings that were related to stroke etiology
      and affected secondary stroke prevention therapy. Imaging findings had already
      suggested cerebral vasculitis in two of these patients. Conclusions: The
      diagnostic yield of routine CSF-analysis in juvenile stroke was remarkably low in
      our study. Our data suggest that CSF-analysis should only be performed if further
      findings raise the suspicion of cerebral vasculitis.

PMID- 30186228
TI  - Presence of Middle Cerebellar Peduncle Sign in FMR1 Premutation Carriers Without
      Tremor and Ataxia.
AB  - Here we report five cases of male FMR1 premutation carriers who present without
      clinical symptoms of the fragile X-associated tremor/ataxia syndrome (FXTAS), but
      who on MRI demonstrate white matter hyperintensities in the middle cerebellar
      peduncles (MCP sign) and other brain regions, a rare finding. MCP sign is the
      major radiological feature of FXTAS; it is therefore remarkable to identify five
      cases in which this MRI finding is present in the absence of tremor and ataxia,
      the major clinical features of FXTAS. Subjects underwent a detailed neurological
      evaluation, neuropsychological testing, molecular testing, and MRI evaluation
      utilizing T2 imaging described here. Additional white matter disease was present
      in the corpus callosum in four of the five cases. However, all cases were
      asymptomatic for motor signs of FXTAS.

PMID- 30186225
TI  - Clinical, Anatomical, and Pathological Features in the Three Variants of Primary
      Progressive Aphasia: A Review.
AB  - Primary progressive aphasias (PPA) are neurodegenerative diseases clinically
      characterized by an early and relatively isolated language impairment. Three main
      clinical variants, namely the nonfluent/agrammatic variant (nfvPPA), the semantic
      variant (svPPA), and the logopenic variant (lvPPA) have been described, each with
      specific linguistic/cognitive deficits, corresponding anatomical and most
      probable pathological features. Since the discovery and the development of
      diagnostic criteria for the PPA variants by the experts in the field, significant
      progress has been made in the understanding of these diseases. This review aims
      to provide an overview of the literature on each of the PPA variant in terms of
      their clinical, anatomical and pathological features, with a specific focus on
      recent findings. In terms of clinical advancements, recent studies have allowed a
      better characterization and differentiation of PPA patients based on both their
      linguistic and non-linguistic profiles. In terms of neuroimaging, techniques such
      as diffusion imaging and resting-state fMRI have allowed a deeper understanding
      of the impact of PPA on structural and functional connectivity alterations beyond
      the well-defined pattern of regional gray matter atrophy. Finally, in terms of
      pathology, despite significant advances, clinico-pathological correspondence in
      PPA remains far from absolute. Nonetheless, the improved characterization of PPA
      has the potential to have a positive impact on the management of patients.
      Improved reliability of diagnoses and the development of reliable in vivo
      biomarkers for underlying neuropathology will also be increasingly important in
      the future as trials for etiology-specific treatments become available.

PMID- 30186230
TI  - Succinate as a Regulator of Hepatic Stellate Cells in Liver Fibrosis.
AB  - The rapid increase of obesity rates worldwide is associated with chronic liver
      injury due to non-alcoholic fatty liver disease and non-alcoholic
      steatohepatitis. Chronic liver inflammation drives hepatic fibrosis, which is a
      highly conserved and coordinated protective response to tissue injury, and is a
      reversible process. Hepatocytes, immune cells, and hepatic stellate cells (HSCs)
      have been identified as key players in the mechanisms of hepatic fibrosis and
      inflammation. During the last decade, succinate, an intermediate of the
      tricarboxylic acid cycle in mitochondrial ATP production, has emerged as an
      important signaling molecule in various diseases. Succinate acts as an
      extracellular ligand for G-protein coupled receptor 91, also known as succinate
      receptor 1, which is mainly expressed in the kidney, heart, liver, immune cells,
      and retinal cells, suggesting a widespread function in cellular metabolism.
      Furthermore, succinate stabilizes hypoxia-inducible factor-1alpha in immune cells
      and tumors as a signaling molecule, and has been shown to post-translationally
      modify proteins. This review summarizes the recent evidence pointing to an
      additional role of succinate in profibrotic signaling, along with its downstream
      signaling pathways, and updates the current state of knowledge on the role of
      succinate in liver fibrosis through its action on HSCs. Further focus on this
      link can help identify succinate, its receptor, and its downstream signaling
      molecules as new targets for the treatment of liver fibrosis.

PMID- 30186229
TI  - Metabolic Profiles Associated With Metformin Efficacy in Cancer.
AB  - Metformin is one of the most commonly prescribed medications for the treatment of
      type 2 diabetes. Numerous reports have suggested potential anti-cancerous and
      cancer preventive properties of metformin, although these findings vary depending
      on the intrinsic properties of the tumor, as well as the systemic physiology of
      patients. These intriguing studies have led to a renewed interest in metformin
      use in the oncology setting, and fueled research to unveil its elusive mode of
      action. It is now appreciated that metformin inhibits complex I of the electron
      transport chain in mitochondria, causing bioenergetic stress in cancer cells, and
      rendering them dependent on glycolysis for ATP production. Understanding the mode
      of action of metformin and the consequences of its use on cancer cell
      bioenergetics permits the identification of cancer types most susceptible to
      metformin action. Such knowledge may also shed light on the varying results to
      metformin usage that have been observed in clinical trials. In this review, we
      discuss metabolic profiles of cancer cells that are associated with metformin
      sensitivity, and rationalize combinatorial treatment options. We use the concept
      of bioenergetic flexibility, which has recently emerged in the field of cancer
      cell metabolism, to further understand metabolic rearrangements that occur upon
      metformin treatment. Finally, we advance the notion that metabolic fitness of
      cancer cells increases during progression to metastatic disease and the emergence
      of therapeutic resistance. As a result, sophisticated combinatorial approaches
      that prevent metabolic compensatory mechanisms will be required to effectively
      manage metastatic disease.

PMID- 30186231
TI  - Risk and Protective Factors for Child Overweight/Obesity Among Low Socio-Economic
      Populations in Israel: A Cross Sectional Study.
AB  - Background and Aims: Scientific evidence regarding protective factors that
      contribute to healthy weight in childhood is limited and is particularly scarce
      in lower socio-economic populations in different ethnic groups. This study aimed
      to assess the prevalence of biological, behavioral and psychosocial factors for
      child overweight/obesity in Jewish and Arab population groups in Israel, and to
      compare their associations with child overweight/obesity in the two groups.
      Methods: Children aged 5-6 years were randomly selected from 20 Mother and Child
      Health clinics in towns and villages of lowest socio-economic ranking in Northern
      Israel. Children and mothers were invited for a special "One Stop Shop
      Preparation for School" visit which included growth measurements. Questionnaires
      were distributed to mothers for self-report on biological, SES, psychological and
      lifestyle factors. Perinatal and early nutritional data were retrieved from
      clinic records. Multivariate analyses using logistic regression models predicting
      child overweight/obesity were conducted separately for Jewish (N = 371) and Arab
      (N = 575) children. Results: Overweight/obesity (BMI >=85th centile) rates were
      higher in Jewish (25%) than Arab (19%) children. In both Jewish and Arab groups,
      respectively, maternal BMI (OR = 1.10 [95%CI = 1.04, 1.17]; OR = 1.08 [95%CI =
      1.04, 1.13]), and child birthweight (OR = 1.33 [95%CI = 1.04, 1.71]; OR = 1.39
      [95%CI = 1.11, 1.73]) were significant risk factors for overweight/obesity, and
      maternal self-efficacy regarding child's lifestyle was significantly protective
      (OR = 0.49 [95%CI = 0.28, 0.85]; OR = 0.54 [95%CI = 0.34, 0.85]). Additionally,
      four other maternal psychological and child behaviors were significantly
      associated with overweight/obesity in the Jewish group and two child lifestyle
      behavior factors in the Arab group. Moreover, significant interactions indicating
      moderation effects were found only in the Jewish group: maternal education and
      maternal age moderated the effect of maternal BMI on child overweight/obesity. No
      other moderation of risk factors was found. Discussion: In this study of children
      from low SES families, protective factors contributed to healthy child weight
      alongside risk factors for overweight/obesity. They differed between the
      population groups, and fewer variables explained overweight/obesity in Arab
      children. Although further expansion of these findings is required they point at
      the relevance of protective factors, maternal self-efficacy in particular, for
      understanding childhood obesity in specific ethnic contexts and for planning
      culturally adapted prevention programs in disadvantaged populations.

PMID- 30186232
TI  - The acyl-CoA Synthetase, pudgy, Promotes Sleep and Is Required for the
      Homeostatic Response to Sleep Deprivation.
AB  - The regulation of sleep and the response to sleep deprivation rely on multiple
      biochemical pathways. A critical connection is the link between sleep and
      metabolism. Metabolic changes can disrupt sleep, and conversely decreased sleep
      can alter the metabolic environment. There is building evidence that lipid
      metabolism, in particular, is a critical part of mounting the homeostatic
      response to sleep deprivation. We have evaluated an acyl-CoA synthetase, pudgy
      (pdgy), for its role in sleep and response to sleep deprivation. When pdgy
      transcript levels are decreased through transposable element disruption of the
      gene, mutant flies showed lower total sleep times and increased sleep
      fragmentation at night compared to genetic controls. Consistent with disrupted
      sleep, mutant flies had a decreased lifespan compared to controls. pdgy disrupted
      fatty acid handling as pdgy mutants showed increased sensitivity to starvation
      and exhibited lower fat stores. Moreover, the response to sleep deprivation is
      reduced when compared to a control flies. When we decreased the transcript levels
      for pdgy using RNAi, the response to sleep deprivation was decreased compared to
      background controls. In addition, when the pdgy transcription is rescued
      throughout the fly, the response to sleep deprivation is restored. These data
      demonstrate that the regulation and function of acyl-CoA synthetase plays a
      critical role in regulating sleep and the response to sleep deprivation.
      Endocrine and metabolic signals that alter transcript levels of pdgy impact sleep
      regulation or interfere with the homeostatic response to sleep deprivation.

PMID- 30186233
TI  - Leptin Stimulates Cellular Glycolysis Through a STAT3 Dependent Mechanism in
      Tilapia.
AB  - We assessed if leptin, a cytokine hormone known to enhance energy expenditure by
      promoting lipid and carbohydrate catabolism in response to physiologic stress,
      might directly regulate cellular glycolysis. A transcriptomic analysis of
      prolactin cells in the tilapia (Oreochromis mossambicus) pituitary rostral pars
      distalis (RPD) revealed that recombinant leptin (rtLep) differentially regulates
      1,995 genes, in vitro. Machine learning algorithms and clustering analyses show
      leptin influences numerous cellular gene networks including metabolism; protein
      processing, transport, and metabolism; cell cycle and the hypoxia response.
      Leptin stimulates transcript abundance of the glycolytic enzyme glyceraldehyde-3
      phosphate dehydrogenase (gapdh) in a covariate manner to the hypoxic stress gene
      network. Orthogonal tests confirm that rtLepA dose-dependently increases gapdh
      gene expression in the RPD along with transcript abundance of 6-phosphofructo-1
      kinase (pfk1), the rate limiting glycolytic enzyme. Functional testing
      demonstrated that leptin stimulates PFK activity and glycolytic output, while
      Stattic (a STAT3 blocker) was sufficient to suppress these responses, indicating
      leptin stimulates glycolysis through a STAT3-dependent mechanism. Leptin also
      stimulated pfk1 gene expression and lactate production in primary hepatocyte
      incubations in a similar manner to those shown for the pituitary RPD. This work
      characterizes a critical metabolic action of leptin to directly stimulate
      glycolysis across tissue types in a teleost model system, and suggest that leptin
      may promote energy expenditure, in part, by stimulating glycolysis. These data in
      a teleost fish, suggest that one of leptin's ancient, highly-conserved functions
      among vertebrates may be stimulation of glycolysis to facilitate the energetic
      needs associated with various stressors.

PMID- 30186235
TI  - The Role of the Transcription Factor Nuclear Factor-kappa B in Thyroid
      Autoimmunity and Cancer.
AB  - Nuclear factor-kappa B (NF-kappaB) is a ubiquitous transcription factor that is
      involved in inflammatory and immune responses, as well as in regulation of
      expression of many other genes related to cell survival, proliferation, and
      differentiation. In mammals, NF-kappaB comprises five subunits that can bind to
      promoter regions of target genes as homodimers or heterodimers. The most common
      dimer is the p50/p65 heterodimer. The several combinations of dimers that can be
      formed contribute to the heterogeneous regulation of NF-kappaB target genes, and
      this heterogeneity is further increased by interactions of the NF-kappaB dimers
      with other transcription factors, such as steroid hormone receptors, activator
      protein-1 (AP-1), and cAMP response element binding protein (CREB). In the
      thyroid, several studies have demonstrated the involvement of NF-kappaB in
      thyroid autoimmunity, thyroid cancer, and thyroid-specific gene regulation. The
      role of NF-kappaB in thyroid autoimmunity was hypothesized more than 20 years
      ago, after the finding that the binding of distinct NF-kappaB heterodimers to the
      major histocompatibility complex class I gene is hormonally regulated. Further
      studies have shown increased activity of NF-kappaB in thyroid autoimmune diseases
      and in thyroid orbitopathy. Increased activity of NF-kappaB has also been
      observed in thyroid cancer, where it correlates with a more aggressive pattern.
      Of particular interest, mutation of some oncogenes or tumor suppressor genes
      involved in thyroid carcinogenesis results in constitutive activation of the NF
      kappaB pathway. More recently, it has been shown that NF-kappaB also has a role
      in thyroid physiology, as it is fundamental for the expression of the main
      thyroid-specific genes, such as sodium iodide symporter, thyroid peroxidase,
      thyroglobulin, Pax8, and TTF-1 (NKX2-1).

PMID- 30186234
TI  - Dopamine Agonists for Pituitary Adenomas.
AB  - Dopamine agonists (DA) are well established as first-line therapy for
      prolactinomas. These tumors express high levels of dopamine 2 receptors (D2R),
      leading to the strong efficacy of DA in reducing tumor size and hormonal
      secretion. Other pituitary tumor subtypes express D2R to varying degrees, leading
      to an extensive body of research into potential off-label use of DA in non
      prolactinoma pituitary tumors. Preclinical models of Cushing's disease,
      acromegaly, and nonfunctioning pituitary tumors (NFPT) demonstrate D2R expression
      in cell lines and cultured tumors as well as effectiveness of DA in reducing
      hormonal secretion in functioning tumors and arresting tumor proliferation.
      Clinical studies have shown some efficacy of DA in treatment of these tumors. In
      Cushing's disease, DA therapy results in normalization of urinary cortisol levels
      in approximately 25% of patients, but reported rates of tumor shrinkage are very
      low; in acromegaly, DA therapy leads to normalization of insulin-like growth
      factor I and tumor shrinkage in approximately one-third of patients, and improved
      responses when used in combination with somatostatin receptor ligands. Among
      patients with NFPT, pooled results show 30% experience reduction of tumor size
      and 58% show stabilization of disease. DA therapy appears to have some clinical
      benefit in patients with non-prolactinoma pituitary tumors, and may be an option
      for medical therapy in some clinical scenarios.

PMID- 30186236
TI  - Metformin: Focus on Melanoma.
AB  - Metformin is the most common biguanide used in the treatment of diabetes, with
      120 million treated patients worldwide. Metformin decreases hyperglycemia without
      inducing hypoglycemia in diabetic patients and is very well tolerated. The
      principal effects of metformin are to decrease hepatic gluconeogenesis and
      increase glucose absorption by skeletal muscles. These effects are primarily due
      to metformin's action on mitochondria, which requires the activation of metabolic
      checkpoint AMP-activated protein kinase (AMPK). AMPK is implicated in several
      pathways, and following metformin activation, it decreases protein synthesis and
      cell proliferation. Many studies have examined the role of metformin in the
      regulation of cancer cells, particularly its effects on cancer cell proliferation
      and cell death. Encouraging results have been obtained in different types of
      cancers, including prostate, breast, lung, and skin cancers (melanoma).
      Furthermore, many retrospective epidemiological studies in diabetes patients have
      shown that metformin treatment decreased the risk of cancers compared with other
      antidiabetic treatments. In this review, we will discuss the effects of metformin
      on melanoma cells. Together, our novel data demonstrate the importance of
      developing metformin and new biguanide-derived compounds as potential treatments
      against a number of different cancers, particularly melanoma.

PMID- 30186238
TI  - Intraoperative Ultrasound: A Tool to Support Tissue-Sparing Curative Pancreatic
      Resection in Focal Congenital Hyperinsulinism.
AB  - Background: Focal congenital hyperinsulinism (CHI) may be cured by resection of
      the focal, but often non-palpable, pancreatic lesion. The surgical challenge is
      to minimize removal of normal pancreatic tissue. Aim: To evaluate the results of
      intraoperative ultrasound-guided, tissue-sparing pancreatic resection in CHI
      patients at an international expert center. Methods: Retrospective study of CHI
      patients treated at Odense University Hospital, Denmark, between January 2010 and
      March 2017. Results: Of 62 consecutive patients with persistent CHI, 24 (39%) had
      focal CHI by histology after surgery. All patients had a paternal ABCC8 or KCNJ11
      mutation and a focal lesion by 18F-DOPA-PET/CT. Intraoperative ultrasound
      localized the focal lesion in 16/20 patients (sensitivity 0.80), including one
      ectopic lesion in the duodenal wall. Intraoperative ultrasound showed no focal
      lesion in 11/11 patients with diffuse CH (specificity 1.0). The positive
      predictive value for focal histology was 1.0, negative predictive value 0.73.
      Tissue-sparing pancreatic resection (focal lesion enucleation, local resection of
      tail or uncinate process) was performed in 67% (n = 16). In 11/12 having tissue
      sparing resection and intraoperative ultrasound, the location of the focal lesion
      was exactly identified. Eight patients had resection of the pancreatic head or
      head/body, four with Roux-en-Y, three with pancreatico-gastrostomy and one
      without reconstruction. None had severe complications to surgery. Cure of
      hypoglycaemia was seen in all patients after one (n = 21) or two (n = 3)
      pancreatic resections. Conclusion: In focal CHI, tissue-sparing pancreatic
      resection was possible in 67%. Intraoperative ultrasound was a helpful supplement
      to the mandatory use of genetics, preoperative 18F-DOPA-PET/CT and intraoperative
      frozen sections.

PMID- 30186239
TI  - Relative Contributions of Lean and Fat Mass to Bone Mineral Density: Insight From
      Prader-Willi Syndrome.
AB  - Context: Low bone mineral density (BMD) is the most important risk factor for
      fragility fracture. Body weight is a simple screening predictor of difference in
      BMD between individuals. However, it is not clear which component of body weight,
      lean (LM), or fat mass (FM), is associated with BMD. People with the genetic
      disorder of Prader-Willi syndrome (PWS) uniquely have a reduced LM despite
      increased FM. Objective: We sought to define the individual impact of LM and FM
      on BMD by investigating subjects with and without PWS. Design, Setting and
      Participants: This cross-sectional study was conducted at the Clinical Research
      Facility of the Garvan Institute of Medical Research, with PWS and control
      participants recruited from a specialized PWS clinic and from the general public
      by advertisement, respectively. The study involved 11 adults with PWS, who were
      age- and sex-matched with 12 obese individuals (Obese group) and 10 lean
      individuals (Lean group). Main Outcome Measures: Whole body BMD was measured by
      dual-energy X-ray absorptiometry. Total body FM and LM were derived from the
      whole body scan. Differences in BMD between groups were assessed by the analysis
      of covariance model, taking into account the effects of LM and FM. Results: The
      PWS group had significantly shorter height than the lean and obese groups. As
      expected, there was no significant difference in FM between the Obese and PWS
      group, and no significant difference in LM between the Lean and PWS group.
      However, obese individuals had greater LM than lean individuals. BMD in lean
      individuals was significantly lower than in PWS individuals (1.13 g/cm2 vs. 1.21
      g/cm2, p < 0.05) and obese individuals (1.13 g/cm2 vs. 1.25 g/cm2, p < 0.05).
      After adjusting for both LM and FM, there was no significant difference in BMD
      between groups, and the only significant predictor of BMD was LM. Conclusions:
      These data from the human genetic model Prader-Willi syndrome suggest that LM is
      a stronger determinant of BMD than fat mass.

PMID- 30186237
TI  - Deciphering the Roles of PPARgamma in Adipocytes via Dynamic Change of
      Transcription Complex.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma), a ligand-dependent
      transcription factor highly expressed in adipocytes, is a master regulator of
      adipogenesis and lipid storage, a central player in thermogenesis and an active
      modulator of lipid metabolism and insulin sensitivity. As a nuclear receptor
      governing numerous target genes, its specific signaling transduction relies on
      elegant transcriptional and post-translational regulations. Notably, in response
      to different metabolic stimuli, PPARgamma recruits various cofactors and forms
      distinct transcriptional complexes that change dynamically in components and
      epigenetic modification to ensure specific signal transduction. Clinically,
      PPARgamma activation via its full agonists, thiazolidinediones, has been shown to
      improve insulin sensitivity and induce browning of white fat, while undesirably
      induce weight gain, visceral obesity and other adverse effects. Thus, deciphering
      the combinatorial interactions between PPARgamma and its transcriptional partners
      and their preferential regulatory network in the processes of development,
      function and senescence of adipocytes would provide us the molecular basis for
      developing novel partial agonists that promote benefits of PPARgamma signaling
      without detrimental side effects. In this review, we discuss the dynamic
      components and precise regulatory mechanisms of the PPARgamma-cofactors complexes
      in adipocytes, as well as perspectives in treating metabolic diseases via
      specific PPARgamma signaling.

PMID- 30186240
TI  - Management of Amiodarone-Induced Thyrotoxicosis at a Cardiac Transplantation
      Centre.
AB  - Background: Amiodarone-induced thyrotoxicosis (AIT) is associated with
      significant morbidity and mortality, particularly in patients with cardiac
      failure. The aim of the study was to evaluate the management of AIT at a tertiary
      hospital specialising in cardiac failure and transplantation. Methods:
      Retrospective audit of 66 patients treated for AIT by Endocrinology (2007-2016),
      classified as type 1 (T1) or type 2 (T2) based on radiological criteria. Main
      outcome measurements were response rate to initial treatment, time to
      euthyroidism, and frequency/safety of thyroidectomy. Results: Mean age was 60 +/-
      2 years; 80% were male. Sixty-four patients commenced medical treatment:
      thionamides (THIO) in 23, glucocorticoids (GC) in 17 and combination (COMB) in
      24. Median thyroxine (fT4) was 35.1 (31.2-46.7) in THIO, 43.1 (30.4 -60.7) in GC,
      and 60.0 (39.0 ->99.9) pmol/L in COMB (p = 0.01). Initial therapy induced
      euthyroidism in 52%: 70% THIO, 53% GC, and 33% COMB (p = 0.045) by 100 (49-167),
      47 (35-61), and 53 (45-99) days, respectively (p = 0.02). A further 11% became
      euthyroid after transitioning from monotherapy to COMB. Thyroidectomy was
      undertaken in 33%. Patients who underwent thyroidectomy were younger (54 +/- 3
      vs. 63 +/- 2 years; p = 0.03), with higher prevalence of severely impaired left
      ventricular function prior to diagnosis of AIT (38 vs. 18%; p = 0.08). Despite
      median American Society of Anaesthesiologists classification 4, no thyroidectomy
      patient experienced cardiorespiratory complications/death. Conclusions: Patients
      with AIT had limited response to medical treatment. The poorest response was
      observed in COMB group, likely related to greater hyperthyroidism severity.
      Thyroidectomy is safe in patients with severe cardiac failure if performed in a
      centre with cardiac anaesthetic expertise. There should be low threshold for
      proceeding to thyroidectomy in patients with severe AIT and/or cardiac failure.

PMID- 30186241
TI  - HU-Lacking Mutants of Salmonella enterica Enteritidis Are Highly Attenuated and
      Can Induce Protection in Murine Model of Infection.
AB  - Salmonella enterica infection is a major public health concern worldwide,
      particularly when associated with other medical conditions. The serovars
      Typhimurium and Enteritidis are frequently associated with an invasive illness
      that primarily affects immunocompromised adults and children with HIV, malaria,
      or malnutrition. These serovars can also cause infections in a variety of animal
      hosts, and they are the most common isolates in poultry materials. Here, we
      described S. Enteritidis mutants, where hupA and hupB genes were deleted, and
      evaluated their potential use as live-attenuated vaccine candidates. In vitro,
      the mutants behaved like S. Typhimurium described previously, but there were some
      particularities in macrophage invasion and survival experiments. The virulence
      and immunogenicity of the mutant lacking both hupA and hupB (PT4DeltahupAB) were
      evaluated in a BALB/c mice model. This mutant was highly attenuated and could,
      therefore, be administrated at doses higher than 109 CFU/treatment, which was
      sufficient to protect all treated mice challenged with the wild-type parental
      strain with a single dose. Additionally, the PT4DeltahupAB strain induced
      production of specific IgG and IgA antibodies against Salmonella and TH1-related
      cytokines (IFN-gamma and TNF-alpha), indicating that this strain can induce
      systemic and mucosal protection in the murine model. Additional studies are
      needed to better understand the mechanisms that lead to attenuation of the double
      mutant PT4DeltahupAB and to elucidate the immune response induced by immunization
      using this strain. However, our data allow us to state that hupAB mutants could
      be potential candidates to be explore as live-attenuated vaccines.

PMID- 30186243
TI  - Isolation, Diversity, and Growth-Promoting Activities of Endophytic Bacteria From
      Tea Cultivars of Zijuan and Yunkang-10.
AB  - Endophytes are rich in plant tissues and play important roles in plant-microbial
      interactions and plant-growth regulation. Here, endophytic bacteria from two
      closely related tea cultivars of Zijuan and Yunkang-10 were isolated, and the
      diversities were compared. Plant-growth promoting (PGP) activities were
      determined on the dominant groups or nitrogen-fixing genera from the two
      cultivars. Endophytic bacteria were isolated by using of different selective
      media and methods, and the PGP activities were investigated by analytical and
      molecular technologies. A total of 110 isolates of 18 genera belonging to three
      phylums (Proteobacteria, Firmicutes, and Bacteroidetes) were obtained from
      Zijuan, while 164 isolates of 22 genera belonging to two phylums (Proteobacteria
      and Firmicutes) were obtained from Yunkang-10. PGP screening indicated that
      Herbaspirillum spp., Methylobacterium spp., and Brevundimonas spp. showed
      different PGP abilities. The PGP ability decreased in order of Herbaspirillum
      spp., Brevundimonas spp. and Methylobacterium spp., and the majority of
      Methylobacterium spp. did not showed PGP activity of nitrogen-fixation, P
      solubilization, siderophore, indole-3-acetic acid (IAA) production or 1
      aminocyclopropane-1-carboxylate (ACC) deaminase. The study of bacterial community
      and PGP activities confirmed that endophytes in tea plants are constantly
      changing in different seasons and tea cultivars, and the PGP bacteria in Zijuan
      are much abundant than those of Yunkang-10.

PMID- 30186242
TI  - In silico Study of Iron, Zinc and Copper Binding Proteins of Pseudomonas syringae
      pv. lapsa: Emphasis on Secreted Metalloproteins.
AB  - The phytopathogenic bacteria, Pseudomonas syringae pv. lapsa (P. syringae pv.
      lapsa) infects the staple food crop wheat. Metalloproteins play important roles
      in plant-pathogen interactions. Hence, the present work is aimed to predict and
      analyze the iron (Fe), zinc (Zn), and copper (Cu) binding proteins of P. syringae
      pv. lapsa which help in its growth, adaptation, survival and pathogenicity. A
      total of 232 Fe, 307 Zn, and 38 Cu-binding proteins have been identified. The
      functional annotation, subcellular localization and gene ontology enriched
      network analysis revealed their role in wide range of biological activities of
      the phytopathogen. Among the identified metalloproteins, a total of 29 Fe
      binding, 31 Zn-binding, and 5 Cu-binding proteins were found to be secreted in
      nature. These putative secreted metalloproteins may perform diverse cellular and
      biological functions ranging from transport, response to oxidative stress,
      proteolysis, antimicrobial resistance, metabolic processes, protein folding and
      DNA repair. The observations obtained here may provide initial information
      required to draft new schemes to control microbial infections of staple food
      crops and will further help in developing sustainable agriculture.

PMID- 30186244
TI  - Unveiling the Multilocus Sequence Typing (MLST) Schemes and Core Genome
      Phylogenies for Genotyping Chlamydia trachomatis.
AB  - Multilocus sequence typing (MLST) has become a useful tool for studying the
      genetic diversity of important public health pathogens, such as Chlamydia
      trachomatis (Ct). Four MLST schemes have been proposed for Ct (data available
      from Chlamydiales MLST databases). However, the lack of a sole standardized
      scheme represents the greatest limitation regarding typing this species. This
      study was thus aimed at evaluating the usefulness of the four MLST schemes
      available for Ct, describing each molecular marker's pattern and its contribution
      toward a description of intra-specific genetic diversity and population
      structure. The markers for each scheme, showed a variable power of dicrimination,
      exhibiting in some cases over estimation in the determination of Sequence Types
      (STs). However, individual analysis of each locus's typing efficiency and
      discrimination power led to identifying 8 markers as having a suitable pattern
      for intra-specific typing. analyzing the 8 candidate markers gave a combination
      of 3 of these loci as an optimal scheme for identifying a large amount of STs,
      maximizing discrimination power whilst maintaining suitable typing efficiency.
      One scheme was compared against core genome phylogenies, finding a higher typing
      resolution through the last approach. These results confirm once again that
      although complete genome data, in particular from core genome MLST (cgMLST) allow
      a high resolution clustering for Ct isolates. There are combinations of molecular
      markers that could generate equivalent results, with the advantage of
      representing an easy implementation strategy and lower costs leading to
      contribute to the monitoring and molecular epidemiology of Ct.

PMID- 30186245
TI  - Infection-Induced Changes Within the Endocytic Recycling Compartment Suggest a
      Roadmap of Human Cytomegalovirus Egress.
AB  - Human cytomegalovirus (HCMV) is an important pathogen in developing fetuses,
      neonates, and individuals with compromised immune systems. Gaps in our
      understanding of the mechanisms required for virion assembly stand in the way of
      development of antivirals targeting late stages of viral replication. During
      infection, HCMV causes a dramatic reorganization of the host endosecretory
      system, leading to the formation of the cytoplasmic virion assembly complex
      (cVAC), the site of virion assembly. As part of cVAC biogenesis, the composition
      and behavior of endosecretory organelles change. To gain more comprehensive
      understanding of the impact HCMV infection has on components of the cellular
      endocytic recycling compartment (ERC), we used previously published
      transcriptional and proteomic datasets to predict changes in the directionality
      of ERC trafficking. We identified infection-associated changes in gene expression
      that suggest shifts in the balance between endocytic and exocytic recycling
      pathways, leading to formation of a secretory trap within the cVAC. Conversely,
      there was a corresponding shift favoring outbound secretory vesicle trafficking,
      indicating a potential role in virion egress. These observations are consistent
      with previous studies describing sequestration of signaling molecules, such as IL
      6, and the synaptic vesicle-like properties of mature HCMV virions. Our analysis
      enabled development of a refined model incorporating old and new information
      related to the behavior of the ERC during HCMV replication. While limited by the
      paucity of integrated systems-level data, the model provides an informed basis
      for development of experimentally testable hypotheses related to mechanisms
      involved in HCMV virion maturation and egress. Information from such experiments
      will provide a robust roadmap for rational development of novel antivirals for
      HCMV and related viruses.

PMID- 30186246
TI  - Primary Lung Dendritic Cell Cultures to Assess Efficacy of Spectinamide-1599
      Against Intracellular Mycobacterium tuberculosis.
AB  - There is an urgent need to treat tuberculosis (TB) quickly, effectively and
      without side effects. Mycobacterium tuberculosis (Mtb), the causative organism of
      TB, can survive for long periods of time within macrophages and dendritic cells
      and these intracellular bacilli are difficult to eliminate with current drug
      regimens. It is well established that Mtb responds differentially to drug
      treatment depending on its extracellular and intracellular location and
      replicative state. In this study, we isolated and cultured lung derived dendritic
      cells to be used as a screening system for drug efficacy against intracellular
      mycobacteria. Using mono- or combination drug treatments, we studied the action
      of spectinamide-1599 and pyrazinamide (antibiotics targeting slow-growing
      bacilli) in killing bacilli located within lung derived dendritic cells.
      Furthermore, because IFN-gamma is an essential cytokine produced in response to
      Mtb infection and present during TB chemotherapy, we also assessed the efficacy
      of these drugs in the presence and absence of IFN-gamma. Our results demonstrated
      that monotherapy with either spectinamide-1599 or pyrazinamide can reduce the
      intracellular bacterial burden by more than 99.9%. Even more impressive is that
      when TB infected lung derived dendritic cells are treated with spectinamide-1599
      and pyrazinamide in combination with IFN-gamma a strong synergistic effect was
      observed, which reduced the intracellular burden below the limit of detection. We
      concluded that IFN-gamma activation of lung derived dendritic cells is essential
      for synergy between spectinamide-1599 and pyrazinamide.

PMID- 30186247
TI  - The Potential Role of the Dipeptidyl Peptidase-4-Like Activity From the Gut
      Microbiota on the Host Health.
AB  - The Dipeptidyl peptidase-4 (DPP-4) activity influences metabolic, behavioral and
      intestinal disorders through the cleavage of key hormones and peptides. Some
      studies describe the existence of human DPP-4 homologs in commensal bacteria, for
      instance in Prevotella or Lactobacillus. However, the role of the gut microbiota
      as a source of DPP-4-like activity has never been investigated. Through the
      comparison of the DPP-4 activity in the cecal content of germ-free mice (GFM) and
      gnotobiotic mice colonized with the gut microbiota of a healthy subject, we bring
      the proof of concept that a significant DPP-4-like activity occurs in the
      microbiota. By analyzing the existing literature, we propose that DPP-4-like
      activity encoded by the intestinal microbiome could constitute a novel mechanism
      to modulate protein digestion as well as host metabolism and behavior.

PMID- 30186249
TI  - Acinetobacter nosocomialis: Defining the Role of Efflux Pumps in Resistance to
      Antimicrobial Therapy, Surface Motility, and Biofilm Formation.
AB  - Acinetobacter nosocomialis is a member of the Acinetobacter calcoaceticus
      Acinetobacter baumannii (ACB) complex. Increasingly, reports are emerging of the
      pathogenic profile and multidrug resistance (MDR) phenotype of this species. To
      define novel therapies to overcome resistance, we queried the role of the major
      efflux pumps in A. nosocomialis strain M2 on antimicrobial susceptibility
      profiles. A. nosocomialis strains with the following mutations were engineered by
      allelic replacement; DeltaadeB, DeltaadeJ, and DeltaadeB/adeJ. In these isogenic
      strains, we show that the DeltaadeJ mutation increased susceptibility to beta
      lactams, beta-lactam/beta-lactamase inhibitors, chloramphenicol, monobactam,
      tigecycline, and trimethoprim. The DeltaadeB mutation had a minor effect on
      resistance to certain beta-lactams, rifampicin and tigecycline. In addition, the
      DeltaadeJ mutation resulted in a significant decrease in surface motility and a
      minor decrease in biofilm formation. Our results indicate that the efflux pump,
      AdeIJK, has additional roles outside of antibiotic resistance in A. nosocomialis.

PMID- 30186248
TI  - Phylogenomic Classification and the Evolution of Clonal Complex 5 Methicillin
      Resistant Staphylococcus aureus in the Western Hemisphere.
AB  - Clonal complex 5 methicillin-resistant Staphylococcus aureus (CC5-MRSA) includes
      multiple prevalent clones that cause hospital-associated infections in the
      Western Hemisphere. Here, we present a phylogenomic study of these MRSA to reveal
      their phylogeny, spatial and temporal population structure, and the evolution of
      selected traits. We studied 598 genome sequences, including 409 newly generated
      sequences, from 11 countries in Central, North, and South America, and references
      from Asia and Europe. An early-branching CC5-Basal clade is well-dispersed
      geographically, is methicillin-susceptible and MRSA predominantly of ST5-IV such
      as the USA800 clone, and includes separate subclades for avian and porcine
      strains. In the early 1970s and early 1960s, respectively, two clades appeared
      that subsequently underwent major expansions in the Western Hemisphere: a CC5-I
      clade in South America and a CC5-II clade largely in Central and North America.
      The CC5-I clade includes the ST5-I Chilean/Cordobes clone, and the ST228-I South
      German clone as an early offshoot, but is distinct from other ST5-I clones from
      Europe that nest within CC5-Basal. The CC5-II clade includes divergent strains of
      the ST5-II USA100 clone, various other clones, and most known vancomycin
      resistant strains of S. aureus, but is distinct from ST5-II strain N315 from
      Japan that nests within CC5-Basal. The recombination rate of CC5 was much lower
      than has been reported for other S. aureus genetic backgrounds, which indicates
      that recurrence of vancomycin resistance in CC5 is not likely due to an enhanced
      promiscuity. An increased number of antibiotic resistances and decreased number
      of toxins with distance from the CC5 tree root were observed. Of note, the
      expansions of the CC5-I and CC5-II clades in the Western Hemisphere were preceded
      by convergent gains of resistance to fluoroquinolone, macrolide, and lincosamide
      antibiotics, and convergent losses of the staphylococcal enterotoxin p (sep) gene
      from the immune evasion gene cluster of phage phiSa3. Unique losses of surface
      proteins were also noted for these two clades. In summary, our study has
      determined the relationships of different clades and clones of CC5 and has
      revealed genomic changes for increased antibiotic resistance and decreased
      virulence associated with the expansions of these MRSA in the Western Hemisphere.

PMID- 30186250
TI  - Adhesion of Salmonella to Pancreatic Secretory Granule Membrane Major
      Glycoprotein GP2 of Human and Porcine Origin Depends on FimH Sequence Variation.
AB  - Bacterial host tropism is a primary determinant of the range of host organisms
      they can infect. Salmonella serotypes are differentiated into host-restricted and
      host-adapted specialists, and host-unrestricted generalists. In order to
      elucidate the underlying molecular mechanisms of host specificity in Salmonella
      infection, we investigated the role of the intestinal host cell receptor zymogen
      granule membrane glycoprotein 2 (GP2), which is recognized by FimH adhesin of
      type 1 fimbriae found in Enterobacteriaceae. We compared four human and two
      porcine GP2 isoforms. Isoforms were expressed in Sf9 cells as well as in one
      human (HEp-2) and one porcine (IPEC-J2) cell line. FimH genes of 128 Salmonella
      isolates were sequenced and the 10 identified FimH variants were compared
      regarding adhesion (static adhesion assay) and infection (cell line assay) using
      an isogenic model. We expressed and characterized two functional porcine GP2
      isoforms differing in their amino acid sequence to human isoforms by
      approximately 25%. By comparing all isoforms in the static adhesion assay, FimH
      variants were assigned to high, low or no-binding phenotypes. This FimH variant
      dependent binding was neither specific for one GP2 isoform nor for GP2 in
      general. However, cell line infection assays revealed fundamental differences:
      using HEp-2 cells, infection was also FimH variant-specific but mainly
      independent of human GP2. In contrast, this FimH variant dependency was not
      obvious using IPEC-J2 cells. Here, we propose an alternative GP2
      adhesion/infection mechanism whereby porcine GP2 is not a receptor that
      determined host-specificity of Salmonella. Salmonella specialists as well as
      generalists demonstrated similar binding to GP2. Future studies should focus on
      spatial distribution of GP2 isoforms in the human and porcine intestine,
      especially comparing health and disease.

PMID- 30186251
TI  - Human Campylobacteriosis in Italy: Emergence of Multi-Drug Resistance to
      Ciprofloxacin, Tetracycline, and Erythromycin.
AB  - Campylobacter spp. is one of the main cause of bacterial gastroenteritis in the
      world. The increase of antibiotic resistance in this species is a threat to
      public health. A Campylobacter spp. surveillance study was performed in Italy in
      the 2013-2016 period by the Enter-Net Italia network. The most prevalent
      Campylobacter species identified causing gastroenteritis was Campylobacter jejuni
      (73.4%) and 45% of all the annual cases of campylobacteriosis were reported in
      the summer period. High rates of ciprofloxacin and tetracycline resistance in
      Campylobacter spp. have been observed. An increasing percentage of Campylobacter
      coli strains simultaneously resistant to ciprofloxacin, tetracycline and
      erythromycin has been found. Molecular mechanisms of resistance have been
      investigated and the role of efflux pumps evaluated. Antibiotic resistance in
      Campylobacter spp. is an increasing serious threat that requires coordinated
      action to minimize the emergence and spread of antimicrobial resistant strains
      from animals to humans throughout the food chain.

PMID- 30186252
TI  - Genetic and Phenotypic Characterization of Indole-Producing Isolates of
      Pseudomonas syringae pv. actinidiae Obtained From Chilean Kiwifruit Orchards.
AB  - In recent years, Chilean kiwifruit production has been affected by the
      phytopathogen Pseudomonas syringae pv. actinidiae (Psa), which has caused losses
      to the industry. In this study, we report the genotypic and phenotypic
      characterization of 18 Psa isolates obtained from Chilean kiwifruits orchards
      between 2012 and 2016 from different geographic origins. Genetic analysis by
      multilocus sequence analysis (MLSA) using four housekeeping genes (gyrB, rpoD,
      gltA, and gapA) and the identification of type III effector genes suggest that
      the Chilean Psa isolates belong to the Psa Biovar 3 cluster. All of the isolates
      were highly homogenous in regard to their phenotypic characteristics. None of the
      isolates were able to form biofilms over solid plastic surfaces. However, all of
      the isolates formed cellular aggregates in the air-liquid interface. All of the
      isolates, except for Psa 889, demonstrated swimming motility, while only isolate
      Psa 510 demonstrated swarming motility. The biochemical profiles of the isolates
      revealed differences in 22% of the tests in at least one Psa isolate when
      analyzed with the BIOLOG system. Interestingly, all of the isolates were able to
      produce indole using a tryptophan-dependent pathway. PCR analysis revealed the
      presence of the genes aldA/aldB and iaaL/matE, which are associated with the
      production of indole-3-acetic acid (IAA) and indole-3-acetyl-3-L-lysine (IAA
      Lys), respectively, in P. syringae. In addition, IAA was detected in the cell
      free supernatant of a representative Chilean Psa strain. This work represents the
      most extensive analysis in terms of the time and geographic origin of Chilean Psa
      isolates. To our knowledge, this is the first report of Psa being able to produce
      IAA. Further studies are needed to determine the potential role of IAA in the
      virulence of Psa during kiwifruit infections and whether this feature is observed
      in other Psa biovars.

PMID- 30186253
TI  - PGAweb: A Web Server for Bacterial Pan-Genome Analysis.
AB  - An astronomical increase in microbial genome data in recent years has led to
      strong demand for bioinformatic tools for pan-genome analysis within and across
      species. Here, we present PGAweb, a user-friendly, web-based tool for bacterial
      pan-genome analysis, which is composed of two main pan-genome analysis modules,
      PGAP and PGAP-X. PGAweb provides key interactive and customizable functions that
      include orthologous clustering, pan-genome profiling, sequence variation and
      evolution analysis, and functional classification. PGAweb presents features of
      genomic structural dynamics and sequence diversity with different visualization
      methods that are helpful for intuitively understanding the dynamics and evolution
      of bacterial genomes. PGAweb has an intuitive interface with one-click setting of
      parameters and is freely available at http://PGAweb.vlcc.cn/.

PMID- 30186255
TI  - Genetic and Functional Diversity of Bacterial Microbiome in Soils With Long Term
      Impacts of Petroleum Hydrocarbons.
AB  - Soil contamination with petroleum, especially in the area of oil wells, is a
      serious environmental problem. Restoring soil subjected to long-term pollution to
      its original state is very difficult. Under such conditions, unique bacterial
      communities develop in the soil that are adapted to the contaminated conditions.
      Analysis of the structure and function of these microorganisms can be a source of
      valuable information with regard to bioremediation. The aim of this study was to
      evaluate structural and functional diversity of the bacterial communities in
      soils with long-term impacts from petroleum. Samples were taken from the three
      oldest oil wells at the Crude Oil Mine site in Weglowka, Poland; the oldest was
      established in 1888. They were collected at 2 distances: (1) within a radius of
      0.5 m from the oil wells, representing soil strongly contaminated with petroleum;
      and (2) 3 m from the oil wells as the controls. The samples were analyzed by 16S
      rRNA sequencing and the community level physiological profiling (CLPP) method in
      order to better understand both the genetic and functional structure of soil
      collected from under oil wells. Significant differences were found in the soil
      samples with regard to bacterial communities. The soils taken within 0.5 m of the
      oil wells were characterized by the highest biodiversity indexes.
      Alphaproteobacteria, Betaproteobacteria, Gammaproteobacteria were strongly
      correlated with biological activity in these soils. Families of
      Alphaproteobacteria were also dominant, including: Bradyrhizobiaceae,
      Rhizobiaceae, Rhodobacteraceae, Acetobacteraceae, Hyphomicrobiaceae, and
      Sphingomonadaceae. The study showed that the long term contamination of soil
      changes bacterial communities and their metabolic activity. Even so, natural
      bioremediation leads to the formation of specific groups of bacteria that
      actively grow at the site of contamination in the soil.

PMID- 30186254
TI  - Structure-Function Relationships of the Neisserial EptA Enzyme Responsible for
      Phosphoethanolamine Decoration of Lipid A: Rationale for Drug Targeting.
AB  - Bacteria cause disease by two general mechanisms: the action of their toxins on
      host cells and induction of a pro-inflammatory response that can lead to a
      deleterious cytokine/chemokine response (e.g., the so-called cytokine storm)
      often seen in bacteremia/septicemia. These major mechanisms may overlap due to
      the action of surface structures that can have direct and indirect actions on
      phagocytic or non-phagocytic cells. In this respect, the lipid A (endotoxin)
      component of lipopolysaccharide (LPS) possessed by Gram-negative bacteria has
      been the subject of literally thousands of studies over the past century that
      clearly identified it as a key virulence factor in endotoxic shock. In addition
      to its capacity to modulate inflammatory responses, endotoxin can also modulate
      bacterial susceptibility to host antimicrobials, such as the host defense
      peptides termed cationic antimicrobial peptides. This review concentrates on the
      phosphoethanolamine (PEA) decoration of lipid A in the pathogenic species of the
      genus Neisseria [N. gonorrhoeae and N. meningitidis]. PEA decoration of lipid A
      is mediated by the enzyme EptA (formerly termed LptA) and promotes resistance to
      innate defense systems, induces the pro-inflammatory response and can influence
      the in vivo fitness of bacteria during infection. These important biological
      properties have driven efforts dealing with the biochemistry and structural
      biology of EptA that will facilitate the development of potential inhibitors that
      block PEA addition to lipid A.

PMID- 30186256
TI  - Syntrophic Partners Enhance Growth and Respiratory Dehalogenation of
      Hexachlorobenzene by Dehalococcoides mccartyi Strain CBDB1.
AB  - This study investigated syntrophic interactions between chlorinated benzene
      respiring Dehalococcoides mccartyi strain CBDB1 and fermenting partners
      (Desulfovibrio vulgaris, Syntrophobacter fumaroxidans, and Geobacter lovleyi)
      during hexachlorobenzene respiration. Dechlorination rates in syntrophic co
      cultures were enhanced 2-3 fold compared to H2 fed CBDB1 pure cultures (0.23 +/-
      0.04 MUmol Cl- day-1). Syntrophic partners were also able to supply cobalamins to
      CBDB1, albeit with 3-10 fold lower resultant dechlorination activity compared to
      cultures receiving exogenous cyanocobalamin. Strain CBDB1 pure cultures
      accumulated ~1 MUmol of carbon monoxide per 87.5 MUmol Cl- released during
      hexachlorobenzene respiration resulting in decreases in dechlorination activity.
      The syntrophic partners investigated were shown to consume carbon monoxide
      generated by CBDB1, thus relieving carbon monoxide autotoxicity. Accumulation of
      lesser chlorinated chlorobenzene congeners (1,3- and 1,4-dichlorobenzene and
      1,3,5-trichlorobenzene) also inhibited dechlorination activity and their removal
      from the headspace through adsorption to granular activated carbon was shown to
      restore activity. Proteomic analysis revealed co-culturing strain CBDB1 with
      Geobacter lovleyi upregulated CBDB1 genes associated with reductive
      dehalogenases, hydrogenases, formate dehydrogenase, and ribosomal proteins. These
      data provide insight into CBDB1 ecology and inform strategies for application of
      CBDB1 in ex situ hexachlorobenzene destruction technologies.

PMID- 30186257
TI  - Local and Regional Scale Heterogeneity Drive Bacterial Community Diversity and
      Composition in a Polar Desert.
AB  - The distribution of organisms in an environment is neither uniform nor random but
      is instead spatially patterned. The factors that control this patterning are
      complex and the underlying mechanisms are poorly understood. Soil microbes are
      critical to ecosystem function but exhibit highly complex distributions and
      community dynamics due in large part to the scale-dependent effects of
      environmental heterogeneity. To better understand the impact of environmental
      heterogeneity on the distribution of soil microbes, we sequenced the 16S rRNA
      gene from bacterial communities in the microbe-dominated polar desert ecosystem
      of the McMurdo Dry Valleys (MDV), Antarctica. Significant differences in key
      edaphic variables and alpha diversity were observed among the three lake basins
      of the Taylor Valley (Kruskal-Wallis; pH: chi2 = 68.89, P < 0.001, conductivity:
      chi2 = 35.03, P < 0.001, observed species: chi2 = 7.98, P = 0.019 and inverse
      Simpson: chi2 = 18.52, P < 0.001) and each basin supported distinctive microbial
      communities (ANOSIM R = 0.466, P = 0.001, random forest ratio of 14.1). However,
      relationships between community structure and edaphic characteristics were highly
      variable and contextual, ranging in magnitude and direction across regional,
      basin, and local scales. Correlations among edaphic factors (pH and soil
      conductivity) and the relative abundance of specific phyla were most pronounced
      along local environmental gradients in the Lake Fryxell basin where
      Acidobacteria, Bacteroidetes, and Proteobacteria declined while Deinococcus
      Thermus and Gemmatimonadetes increased with soil conductivity (all P < 0.1).
      Species richness was most strongly related to the soil conductivity gradient
      present within this study system. We suggest that the relative importance of pH
      versus soil conductivity in structuring microbial communities is related to the
      length of edaphic gradients and the spatial scale of sampling. These results
      highlight the importance of conducting studies over large ranges of key
      environmental gradients and across multiple spatial scales to assess the
      influence of environmental heterogeneity on the composition and diversity of
      microbial communities.

PMID- 30186258
TI  - Ethanol Dehydrogenase I Contributes to Growth and Sporulation Under Low Oxygen
      Condition via Detoxification of Acetaldehyde in Metarhizium acridum.
AB  - The entomopathogenic fungi encounter hypoxic conditions in both nature and
      artificial culture. Alcohol dehydrogenases (ADHs) are a group of oxidoreductases
      that occur in many organisms. Here we demonstrate that an alcohol dehydrogenase
      I, MaADH1, in the locust-specific fungal pathogen, Metarhizium acridum, functions
      in acetaldehyde detoxification mechanism under hypoxic conditions in growth and
      sporulation. The MaADH1 was highly expressed in sporulation stage under hypoxic
      conditions. Compared with a wild-type strain, the DeltaMaADH1 mutant showed
      inhibited growth and sporulation under hypoxic conditions, but no impairment
      under normal conditions. Under hypoxic conditions, DeltaMaADH1 mutant produced
      significant decreased alcohol, but significant increased acetaldehyde compared to
      wild type. M. acridum was sensitive to exogenous acetaldehyde, exhibiting an
      inhibited growth and sporulation with acetaldehyde added in the medium. MaADH1
      did not affect virulence. Our results indicated that the MaADH1 was critical to
      growth and sporulation under hypoxic stress by detoxification of acetaldehyde in
      M. acridum.

PMID- 30186259
TI  - Bacillus subtilis HelD, an RNA Polymerase Interacting Helicase, Forms Amyloid
      Like Fibrils.
AB  - HelD, an RNA polymerase binding protein from Bacillus subtilis, stimulates
      transcription and helps in timely adaptation of cells under diverse environmental
      conditions. At present, no structural information is available for HelD. In the
      current study, we performed size exclusion chromatography coupled to small angle
      X-ray scattering (SEC-SAXS) which suggests that HelD is predominantly monomeric
      and globular in solution. Using combination of size exclusion chromatography and
      analytical ultracentrifugation, we also show that HelD has a tendency to form
      higher order oligomers in solution. CD experiments suggest that HelD has both
      alpha-helical (~35%) and beta sheet (~26%) secondary structural elements. Thermal
      melting experiments suggest that even at 90 degrees C, there is only about 30%
      loss in secondary structural contents with Tm of 44 degrees C. However, with the
      increase in temperature, there was a gain in the beta-sheet content and
      significant irreversible loss of alpha-helical content. Using a combination of X
      ray fiber diffraction analysis, and dye based assays including Thioflavin-T based
      fluorescence and Congo red binding assays, we discovered that HelD forms amyloid
      like fibrils at physiologically relevant conditions in vitro. Using confocal
      imaging, we further show that HelD forms amyloid inclusions in Escherichia coli.
      Bioinformatics-based sequence analysis performed using three independent web
      based servers suggests that HelD has more than 20 hot-spots spread across the
      sequence that may aid the formation of amyloid-like fibrils. This discovery adds
      one more member to the growing list of amyloid or amyloid-like fibril forming
      cytosolic proteins in bacteria. Future studies aimed at resolving the function of
      amyloid-like fibrils or amyloid inclusions may help better understand their role,
      if any, in the bacterial physiology.

PMID- 30186260
TI  - Further Spread of a blaKPC-Harboring Untypeable Plasmid in Enterobacteriaceae in
      China.
AB  - The wide spread of Klebsiella pneumoniae carbapenemase (KPC)-producing
      Enterobacteriaceae is great threat to public health in China. Plasmids are among
      the major factors mediating blaKPC gene dissemination. A total of 156 carbapenem
      resistant Enterobacteriaceae (CRE) isolates were identified in a tertiary
      hospital in China. Six KPC-producing isolates, namely, E. coli (n = 2), E.
      asburiae (n = 1), C. freundii (n = 1), C. portucalensis (n = 1), and C. koseri (n
      = 1), tested positive for the pCKPC18-1-like untypeable plasmid, which was
      described recently in C. freundii. All 6 plasmids could be easily transferred
      into E. coli by chemical transformation or conjugation and were confirmed by
      sequencing to harbor blaKPC-2. Multilocus PCRs and EcoRI-RFLP revealed that the 6
      untypeable plasmids belonged to 2 isoforms. High-throughput sequencing of
      representative plasmids (pCP40 and pEC86) led to the identification of 2 plasmids
      that shared the common backbone genes repA, DnaJ, StpA, and yafB, which were
      characteristic of the untypeable plasmid, and had similar blaKPC-2 genetic
      contexts of the Tn3-Tn4401 chimera. Nucleotide comparison revealed high sequence
      identity of the 2 plasmids with previously reported blaKPC-2-carrying untypeable
      plasmids. In particular, the pCP40 plasmid from C. portucalensis and the
      pHS062105-3 plasmid from K. pneumoniae differed by only 20 single-nucleotide
      polymorphisms (SNPs). To the best of our knowledge, this is the first report of a
      blaKPC-harboring untypeable plasmid spread into E. coli, E. asburiae, and C.
      koseri strains in China.

PMID- 30186261
TI  - Acquisition of Innate Inhibitor Resistance and Mammalian Pathogenicity During Egg
      Adaptation by the H9N2 Avian Influenza Virus.
AB  - An H9N2 avian influenza A virus (AIV), A/chicken/Korea/01310/2001 (01310-CE20),
      was established after 20 passages of influenza A/chicken/Korea/01310/2001 (01310
      CE2) virus through embryonated chicken eggs (ECEs). As a result of this process,
      the virus developed highly replicative and pathogenic traits within the ECEs
      through adaptive mutations in hemagglutinin (HA: T133N, V216G, and E439D) and
      neuraminidase (NA: 18-amino acid deletion and E54D). Here, we also established
      that 01310-CE20 acquired resistance to innate inhibitors present in the egg white
      during these passages. To investigate the role of egg-adapted mutations in
      resistance to innate inhibitors, we generated four PR8-derived recombinant
      viruses using various gene combinations of HA and NA from 01310-CE2 and 01310
      CE20 (rH2N2, rH2N20, rH20N2, and rH20N20). As expected, rH20N20 showed
      significantly higher replication efficiency in MDCK cells and mouse lungs, and
      demonstrated greater pathogenicity in mice. In addition, rH20N20 showed higher
      resistance to innate inhibitors than the other viruses. By using a loss-of
      function mutant and receptor-binding assay, we demonstrated that a T133N site
      directed mutation created an additional N-glycosite at position 133 in rH20N20.
      Further, this mutation played a crucial role in viral replication and resistance
      to innate inhibitors by modulating the binding affinities to avian-like and
      mammalian-like receptors on the host cells and inhibitors. Thus, egg-adapted HA
      and NA may exacerbate the mammalian pathogenicity of AIVs by defying host innate
      inhibitors as well as by increasing replication efficiency in mammalian cells.

PMID- 30186262
TI  - Evaluating the Safety of Potential Probiotic Enterococcus durans KLDS6.0930 Using
      Whole Genome Sequencing and Oral Toxicity Study.
AB  - Enterococcus durans KLDS6.0930 has previously been shown to have probiotic
      potential. However, being a potential clinical pathogen, it becomes necessary to
      evaluate its safety status for novel potential probiotic use. The purpose of this
      study is to systematically evaluate the safety of E. durans KLDS6.0930 based on
      its genomics, phenotypic characteristics and oral toxicity. The complete genome
      of E. durans KLDS6.0930 was sequenced and analyzed for safety-related genes.
      Antibiotic susceptibility and the production of harmful metabolites were tested.
      A 28-day repeated oral dose toxicity test was implemented in rats. In vitro, E.
      durans KLDS6.0930 was resistant to five antibiotics, with intrinsic resistances
      to four antibiotics and no identified genes for the last. E. durans KLDS6.0930
      was not hemolytic and virulence factors were non-functional in its genome. E.
      durans KLDS6.0930 produced a small amount of tyramine and phenethylamine; genes
      encoding tyramine decarboxylase were identified. In addition, genotype and
      phenotype analyses showed that the strain did not have the ability to generate D
      lactic acid, indole, or nitroreductase. In vivo, E. durans KLDS6.0930 did not
      induce adverse effects on the organs, hematological and serum biochemical
      parameters, or cecal bacterial populations in the oral toxicity test. These
      results indicate that E. durans KLDS6.0930 can be safely used as a potential
      probiotic for human consumption and animal feed.

PMID- 30186264
TI  - Oxygen Limitation Enhances the Antimicrobial Activity of Fosfomycin in
      Pseudomonas aeruginosa Following Overexpression of glpT Which Encodes Glycerol-3
      Phosphate/Fosfomycin Symporter.
AB  - Fosfomycin is resurfacing as a "last resort drug" to treat infections caused by
      multidrug resistant pathogens. This drug has a remarkable benefit in that its
      activity increases under oxygen-limited conditions unlike other commonly used
      antimicrobials such as beta-lactams, fluoroquinolones and aminoglycosides.
      Especially, utility of fosfomycin has being evaluated with particular interest to
      treat chronic biofilm infections caused by Pseudomonas aeruginosa because it
      often encounters anaerobic situations. Here, we showed that P. aeruginosa PAO1,
      commonly used in many laboratories, becomes more susceptible to fosfomycin when
      grown anaerobically, and studied on how fosfomycin increases its activity under
      anaerobic conditions. Results of transport assay and gene expression study
      indicated that PAO1 cells grown anaerobically exhibit a higher expression of glpT
      encoding a glycerol-3-phosphate transporter which is responsible for fosfomycin
      uptake, then lead to increased intracellular accumulation of the drug. Elevated
      expression of glpT in anaerobic cultures depended on ANR, a transcriptional
      regulator that is activated under anaerobic conditions. Purified ANR protein
      bound to the DNA fragment from glpT region upstream, suggesting it is an
      activator of glpT gene expression. We found that increased susceptibility to
      fosfomycin was also observed in a clinical isolate which has a promoted biofilm
      phenotype and its glpT and anr genes are highly conserved with those of PAO1. We
      conclude that increased antibacterial activity of fosfomycin to P. aeruginosa
      under anaerobic conditions is attributed to elevated expression of GlpT following
      activation of ANR, then leads to increased uptake of the drug.

PMID- 30186263
TI  - Structural and Functional Alterations in the Microbial Community and
      Immunological Consequences in a Mouse Model of Antibiotic-Induced Dysbiosis.
AB  - The aim of this study was to establish continuous therapeutic-dose ampicillin
      (CTDA)-induced dysbiosis in a mouse model, mimicking typical adult exposure, with
      a view to using this to assess its impact on gut microbiota, intestinal
      metabolites and host immune responses. Mice were exposed to ampicillin for 14
      days and antibiotic-induced dysbiosis was evaluated by alteration of microbiota
      and gut permeability. The cecal index was increased in the CTDA group, and the
      gut permeability indicated by fluorescent dextran, endotoxin and D-Lactate in the
      serum was significantly increased after antibiotic use. The tight-junction
      proteins ZO-1 and occludin in the colon were reduced to half the control level in
      CTDA. We found that alpha-diversity was significantly decreased in mice receiving
      CTDA, and microbial community structure was altered compared with the control.
      Key taxa were identified as CTDA-specific, and the relative abundance of
      Enterococcus and Klebsiella was particularly enriched while Lachnospiraceae,
      Coprobacillus and Dorea were depleted after antibiotic treatment. In particular,
      a significant increase in succinate and a reduction in butyrate was detected in
      CTDA mice, and the triggering of NF-kappaB enhancement reflected that the host
      immune response was influenced by ampicillin use. The observed perturbation of
      the microbiota was accompanied by modulation of inflammatory state; this included
      increase in interferon-gamma and RegIIIgamma, and a decrease in secretory IgA in
      the colon mucosa. This study allowed us to identify the key taxa associated with
      an ampicillin-induced state of dysbiosis in mice and to characterize the
      microbial communities via molecular profiling. Thus, this work describes the
      bacterial ecology of antibiotic exposure model in combination with host
      physiological characteristics at a detailed level of microbial taxa.

PMID- 30186265
TI  - Methods for Lipid Droplet Biophysical Characterization in Flaviviridae
      Infections.
AB  - Lipid droplets (LDs) are intracellular organelles for neutral lipid storage,
      originated from the endoplasmic reticulum. They play an essential role in lipid
      metabolism and cellular homeostasis. In fact, LDs are complex organelles,
      involved in many more cellular processes than those initially proposed. They have
      been extensively studied in the context of LD-associated pathologies. In
      particular, LDs have emerged as critical for virus replication and assembly.
      Viruses from the Flaviviridae family, namely dengue virus (DENV), hepatitis C
      virus (HCV), West Nile virus (WNV), and Zika virus (ZIKV), interact with LDs to
      usurp the host lipid metabolism for their own viral replication and pathogenesis.
      In general, during Flaviviridae infections it is observed an increasing number of
      host intracellular LDs. Several viral proteins interact with LDs during different
      steps of the viral life cycle. The HCV core protein and DENV capsid protein,
      extensively interact with LDs to regulate their replication and assembly.
      Detailed studies of LDs in viral infections may contribute for the development of
      possible inhibitors of key steps of viral replication. Here, we reviewed
      different techniques that can be used to characterize LDs isolated from infected
      or non-infected cells. Microscopy studies have been commonly used to observe LDs
      accumulation and localization in infected cell cultures. Fluorescent dyes, which
      may affect LDs directly, are widely used to probe LDs but there are also
      approaches that do not require the use of fluorescence, namely stimulated Raman
      scattering, electron and atomic force microscopy-based approaches. These three
      are powerful techniques to characterize LDs morphology. Raman scattering
      microscopy allows studying LDs in a single cell. Electron and atomic force
      microscopies enable a better characterization of LDs in terms of structure and
      interaction with other organelles. Other biophysical techniques, such as dynamic
      light scattering and zeta potential are also excellent to characterize LDs in
      terms of size in a simple and fast way and test possible LDs interaction with
      viral proteins. These methodologies are reviewed in detail, in the context of
      viral studies.

PMID- 30186266
TI  - Coumarin Reduces Virulence and Biofilm Formation in Pseudomonas aeruginosa by
      Affecting Quorum Sensing, Type III Secretion and C-di-GMP Levels.
AB  - As one of the major pathogens in wound infections, Pseudomonas aeruginosa
      produces several virulence factors and forms biofilms; these processes are under
      the regulation of various quorum sensing (QS) systems. Therefore, QS has been
      regarded as a promising target to treat P. aeruginosa infections. In the present
      study, we evaluated the effect of the plant-derived QS inhibitor coumarin on P.
      aeruginosa biofilms and virulence. Coumarin inhibited QS in the P. aeruginosa
      QSIS2 biosensor strain, reduced protease and pyocyanin production, and inhibited
      biofilm formation in microtiter plates in different P. aeruginosa strains. The
      effects of coumarin in inhibiting biofilm formation in an in vitro wound model
      and reducing P. aeruginosa virulence in the Lucilia sericata infection model were
      strain-dependent. Transcriptome analysis revealed that several key genes involved
      in the las, rhl, Pseudomonas quinolone signal (PQS), and integrated QS (IQS)
      systems were downregulated in coumarin-treated biofilms of P. aeruginosa PAO1.
      Coumarin also changed the expression of genes related to type III secretion and
      cyclic diguanylate (c-di-GMP) metabolism. The cellular c-di-GMP level of P.
      aeruginosa PAO1 and recent clinical P. aeruginosa strains was significantly
      reduced by coumarin. These results provide new evidence for the possible
      application of coumarin as an anti-biofilm and anti-virulence agent against P.
      aeruginosa in wound infections.

PMID- 30186268
TI  - Detection by Direct Next Generation Sequencing Analysis of Emerging Enterovirus
      D68 and C109 Strains in an Environmental Sample From Scotland.
AB  - Background: Human enteroviruses (EVs) have been linked with severe disease and
      syndromes as varied as acute respiratory illness, myocarditis, and flaccid
      paralysis. With global polio eradication on sight the focus of clinical
      investigations has expanded to the identification of other EV serotypes
      associated with severe neurological conditions such as EV-D68, responsible for
      large outbreaks in 2014 and 2016 that spread worldwide and were related with
      severe respiratory disease leading to acute myelitis in some cases. New EV
      serotypes with epidemic potential continue to emerge such as EV-C104, EV-C105, EV
      C109, and EV-C117 identified in respiratory samples in recent years. Methods: We
      used a next generation sequencing (NGS) approach to detect multiple EV serotypes
      directly in a sewage concentrate from Glasgow (Scotland, United Kingdom)
      generating whole-capsid nucleotide sequences that were compared to sequences of
      cell culture isolates from this sewage sample and clinical EV isolates from
      GenBank. Results: Thirteen different serotypes belonging to all four A, B, C, and
      D EV species were identified in the sewage concentrate. EV strains closely
      related to EV-D68 epidemic isolates of B3 lineage reported in the United States
      and Europe in 2016 and to EV-C109 respiratory isolates found in Denmark and
      Netherlands in 2015 were identified. Conclusion: Environmental surveillance (ES)
      can effectively detect EV circulation in human populations. The use of NGS for ES
      can help overcoming the limitations of traditional cell culture and sequencing
      methods, which are selective and biased, and can contribute to the early
      detection and assessment of spread of emerging EV pathogens.

PMID- 30186267
TI  - Active HHV-6 Infection of Cerebellar Purkinje Cells in Mood Disorders.
AB  - Early-life infections and associated neuroinflammation is incriminated in the
      pathogenesis of various mood disorders. Infection with human roseoloviruses, HHV
      6A and HHV-6B, allows viral latency in the central nervous system and other
      tissues, which can later be activated causing cognitive and behavioral
      disturbances. Hence, this study was designed to evaluate possible association of
      HHV-6A and HHV-6B activation with three different groups of psychiatric patients.
      DNA qPCR, immunofluorescence and FISH studies were carried out in post-mortem
      posterior cerebellum from 50 cases each of bipolar disorder (BPD), schizophrenia,
      15 major depressive disorder (MDD) and 50 appropriate control samples obtained
      from two well-known brain collections (Stanley Medical Research Institute). HHV
      6A and HHV-6B late proteins (indicating active infection) and viral DNA were
      detected more frequently (p < 0.001 for each virus) in human cerebellum in MDD
      and BPD relative to controls. These roseolovirus proteins and DNA were found less
      frequently in schizophrenia cases. Active HHV-6A and HHV-6B infection in
      cerebellar Purkinje cells were detected frequently in BPD and MDD cases.
      Furthermore, we found a significant association of HHV-6A infection with reduced
      Purkinje cell size, suggesting virus-mediated abnormal Purkinje cell function in
      these disorders. Finally, gene expression analysis of cerebellar tissue revealed
      changes in pathways reflecting an inflammatory response possibly to HHV-6A
      infection. Our results provide molecular evidence to support a role for active
      HHV-6A and HHV-6B infection in BPD and MDD.

PMID- 30186269
TI  - Pseudomonas-Specific NGS Assay Provides Insight Into Abundance and Dynamics of
      Pseudomonas Species Including P. aeruginosa in a Cooling Tower.
AB  - Pseudomonas species are frequent inhabitants of freshwater environments and
      colonizers of water supply networks via bioadhesion and biofilm formation. P.
      aeruginosa is the species most commonly associated with human disease, causing a
      wide variety of infections with links to its presence in freshwater systems.
      Though several other Pseudomonas species are of ecological and public health
      importance, little knowledge exists regarding environmental abundances of these
      species. In the present study, an Illumina-based next-generation sequencing (NGS)
      approach using Pseudomonas-specific primers targeting the 16S rRNA gene was
      evaluated and applied to a set of freshwater samples from different environments
      including a cooling tower sampled monthly during 2 years. Our approach showed
      high in situ specificity and accuracy. NGS read counts revealed a precise
      quantification of P. aeruginosa and a good correlation with the absolute number
      of Pseudomonas genome copies in a validated genus-specific qPCR assay,
      demonstrating the ability of the NGS approach to determine both relative and
      absolute abundances of Pseudomonas species and P. aeruginosa. The
      characterization of Pseudomonas communities in cooling tower water allowed us to
      identify 43 phylotypes, with P. aeruginosa being the most abundant. A shift
      existed within each year from a community dominated by phylotypes belonging to P.
      fluorescens and P. oleovorans phylogenetic groups to a community where P.
      aeruginosa was highly abundant. Co-occurrence was observed between P. aeruginosa
      and other phylotypes of P. aeruginosa group as well as the potentially pathogenic
      species P. stutzeri, but not with phylotypes of the P. fluorescens group,
      indicating the need to further investigate the metabolic networks and ecological
      traits of Pseudomonas species. This study demonstrates the potential of deep
      sequencing as a valuable tool in environmental diagnostics and surveillance of
      health-related pathogens in freshwater environments.

PMID- 30186270
TI  - New Alpiniamides From Streptomyces sp. IB2014/011-12 Assembled by an Unusual
      Hybrid Non-ribosomal Peptide Synthetase Trans-AT Polyketide Synthase Enzyme.
AB  - The environment of Lake Baikal is a well-known source of microbial diversity. The
      strain Streptomyces sp. IB2014/011-12, isolated from samples collected at Lake
      Baikal, was found to exhibit potent activity against Gram-positive bacteria.
      Here, we report isolation and characterization of linear polyketide alpiniamide A
      (1) and its new derivatives B-D (2-5). The structures of alpiniamides A-D were
      established and their relative configuration was determined by combination of
      partial Murata's method and ROESY experiment. The absolute configuration of
      alpiniamide A was established through Mosher's method. The gene cluster,
      responsible for the biosynthesis of alpiniamides (alp) has been identified by
      genome mining and gene deletion experiments. The successful expression of the
      cloned alp gene cluster in a heterologous host supports these findings. Analysis
      of the architecture of the alp gene cluster and the feeding of labeled precursors
      elucidated the alpiniamide biosynthetic pathway. The biosynthesis of alpiniamides
      is an example of a rather simple polyketide assembly line generating unusual
      chemical diversity through the combination of domain/module skipping and double
      bond migration events.

PMID- 30186273
TI  - Effects of Reforestation on the Structure and Diversity of Bacterial Communities
      in Subtropical Low Mountain Forest Soils.
AB  - Reforestation with different tree species could alter soil properties and in turn
      affect the bacterial community. However, the effects of long-term reforestation
      on bacterial community structure and diversity of subtropical forest soils are
      poorly understood. In the current study, we applied error-corrected barcoded
      pyrosequencing to characterize the differences in the soil bacterial community in
      a low mountain, subtropical forest subjected to reforestation. The communities
      were sampled in the summer and winter from a native broadleaved forest (BROAD
      Nat) and two adjacent coniferous plantations, a Calocedrus formosana forest of 80
      years (CONIF-80) and a Cunninghamia konishii forest of 40 years (CONIF-40). The
      soil bacterial communities among three forest types were dominated by
      Acidobacteria and Alphaproteobacteria. The distribution of abundant genera among
      communities was different. Based on the Shannon diversity index, the bacterial
      alpha diversity of CONIF-40 community was significantly higher than that in the
      CONIF-80 and BROAD-Nat soils. In both of the coniferous plantations, the soil
      bacterial diversity in summer was also higher than that in winter. Distribution
      of some abundant phylogenetic groups, K-shuff and redundancy analysis of beta
      diversity among communities showed that the bacterial structure of three soil
      communities differed between two seasons. These results suggest that seasonal
      differences influence the diversity and structure of bacterial soil communities
      and that the communities remain different even after a long period of
      reforestation.

PMID- 30186272
TI  - Butyrate Protects Mice Against Methionine-Choline-Deficient Diet-Induced Non
      alcoholic Steatohepatitis by Improving Gut Barrier Function, Attenuating
      Inflammation and Reducing Endotoxin Levels.
AB  - Butyrate exerts protective effects against non-alcoholic steatohepatitis (NASH),
      but the underlying mechanisms are unclear. We aimed to investigate the role of
      butyrate-induced gut microbiota and metabolism in NASH development. Sixty-five
      C57BL/6J mice were divided into four groups (n = 15-17 per group) and were fed
      either a methionine-choline-sufficient (MCS) diet or methionine-choline-deficient
      (MCD) diet with or without sodium butyrate (SoB; 0.6 g/kg body weight)
      supplementation for 6 weeks. Liver injury, systematic inflammation, and gut
      barrier function were determined. Fecal microbiome and metabolome were analyzed
      using 16S rRNA deep sequencing and gas chromatography-mass spectrometry (GC-MS).
      The results showed that butyrate alleviated the MCD diet-induced microbiome
      dysbiosis, as evidenced by a significantly clustered configuration separate from
      that of the MCD group and by the depletion of Bilophila and Rikenellaceae and
      enrichment of promising probiotic genera Akkermansia, Roseburia, Coprococcus,
      Coprobacillus, Delftia, Sutterella, and Coriobacteriaceae genera. The fecal
      metabolomic profile was also substantially improved by butyrate; several butyrate
      responsive metabolites involved in lipid metabolism and other pathways, such as
      stearic acid, behenic acid, oleic acid, linoleic acid, squalene, and arachidonic
      acid, were identified. Correlation analysis of the interaction matrix indicated
      that the modified gut microbiota and fecal metabolites induced by butyrate were
      strongly correlated with the alleviation of hepatic injury, fibrosis progression,
      inflammation, and lipid metabolism and intestinal barrier dysfunction. In
      conclusion, our results demonstrated that butyrate exerts protective effects
      against NASH development, and these effects may be driven by the protective gut
      microbiome and metabolome induced by butyrate. This study thus provides new
      insights into NASH prevention.

PMID- 30186271
TI  - Inflammatory and Pro-resolving Lipids in Trypanosomatid Infections: A Key to
      Understanding Parasite Control.
AB  - Pathogenic trypanosomatids (Trypanosoma cruzi, Trypanosoma brucei, and Leishmania
      spp.) are protozoan parasites that cause neglected diseases affecting millions of
      people in Africa, Asia, and the Americas. In the process of infection,
      trypanosomatids evade and survive the immune system attack, which can lead to a
      chronic inflammatory state that induces cumulative damage, often killing the host
      in the long term. The immune mediators involved in this process are not entirely
      understood. Most of the research on the immunologic control of protozoan
      infections has been focused on acute inflammation. Nevertheless, when this
      process is not terminated adequately, permanent damage to the inflamed tissue may
      ensue. Recently, a second process, called resolution of inflammation, has been
      proposed to be a pivotal process in the control of parasite burden and
      establishment of chronic infection. Resolution of inflammation is an active
      process that promotes the normal function of injured or infected tissues. Several
      mediators are involved in this process, including eicosanoid-derived lipids,
      cytokines such as transforming growth factor (TGF)-beta and interleukin (IL)-10,
      and other proteins such as Annexin-V. For example, during T. cruzi infection, pro
      resolving lipids such as 15-epi-lipoxin-A4 and Resolvin D1 have been associated
      with a decrease in the inflammatory changes observed in experimental chronic
      heart disease, reducing inflammation and fibrosis, and increasing host survival.
      Furthermore, Resolvin D1 modulates the immune response in cells of patients with
      Chagas disease. In Leishmania spp. infections, pro-resolving mediators such as
      Annexin-V, lipoxins, and Resolvin D1 are related to the modulation of cutaneous
      manifestation of the disease. However, these mediators seem to have different
      roles in visceral or cutaneous leishmaniasis. Finally, although T. brucei
      infections are less well studied in terms of their relationship with
      inflammation, it has been found that arachidonic acid-derived lipids act as key
      regulators of the host immune response and parasite burden. Also, cytokines such
      as IL-10 and TGF-beta may be related to increased infection. Knowledge about the
      inflammation resolution process is necessary to understand the host-parasite
      interplay, but it also offers an interesting opportunity to improve the current
      therapies, aiming to reduce the detrimental state induced by chronic protozoan
      infections.

PMID- 30186276
TI  - Effects of Sourdough on FODMAPs in Bread and Potential Outcomes on Irritable
      Bowel Syndrome Patients and Healthy Subjects.
AB  - Background: Fermentable oligosaccharides, disaccharides, monosaccharides and
      polyols (FODMAPs) are an heterogeneous group of compounds that can be poorly
      digested and may have a range of effects on gastrointestinal processes. FODMAPs
      are found in a wide variety of foods, including bread. FODMAPs' intake is
      associated with the onset of symptoms of irritable bowel syndrome (IBS). On the
      other hand, some FODMAPs contribute to the healthy maintenance of intestinal
      microbiota. Volume increase of bread dough commonly relies on the use of two
      biological leavening agents, sourdough and baker's yeast and, in some cases, a
      combination of both. Scope and Approach: The main objective of this review is to
      discuss the association between FODMAPs and IBS, beneficial effects of FODMAPs on
      healthy subjects and potential impact of biological leavening agents on FODMAPs
      content of bread. Key Findings and Conclusion: Given that yeasts and lactic acid
      bacteria, the dominant microorganisms in sourdough, may degrade FODMAPs, it would
      be possible to modulate the FODMAPs concentration in bread, thus positively
      affecting consumers' health.

PMID- 30186274
TI  - Metabolic Reprogramming of Clostridioides difficile During the Stationary Phase
      With the Induction of Toxin Production.
AB  - The obligate anaerobe, spore forming bacterium Clostridioides difficile (formerly
      Clostridium difficile) causes nosocomial and community acquired diarrhea often
      associated with antibiotic therapy. Major virulence factors of the bacterium are
      the two large clostridial toxins TcdA and TcdB. The production of both toxins was
      found strongly connected to the metabolism and the nutritional status of the
      growth environment. Here, we systematically investigated the changes of the gene
      regulatory, proteomic and metabolic networks of C. difficile 630Deltaerm
      underlying the adaptation to the non-growing state in the stationary phase.
      Integrated data from time-resolved transcriptome, proteome and metabolome
      investigations performed under defined growth conditions uncovered multiple
      adaptation strategies. Overall changes in the cellular processes included the
      downregulation of ribosome production, lipid metabolism, cold shock proteins,
      spermine biosynthesis, and glycolysis and in the later stages of riboflavin and
      coenzyme A (CoA) biosynthesis. In contrast, different chaperones, several
      fermentation pathways, and cysteine, serine, and pantothenate biosynthesis were
      found upregulated. Focusing on the Stickland amino acid fermentation and the
      central carbon metabolism, we discovered the ability of C. difficile to replenish
      its favored amino acid cysteine by a pathway starting from the glycolytic 3
      phosphoglycerate via L-serine as intermediate. Following the growth course, the
      reductive equivalent pathways used were sequentially shifted from proline via
      leucine/phenylalanine to the central carbon metabolism first to butanoate
      fermentation and then further to lactate fermentation. The toxin production was
      found correlated mainly to fluxes of the central carbon metabolism. Toxin
      formation in the supernatant was detected when the flux changed from butanoate to
      lactate synthesis in the late stationary phase. The holistic view derived from
      the combination of transcriptome, proteome and metabolome data allowed us to
      uncover the major metabolic strategies that are used by the clostridial cells to
      maintain its cellular homeostasis and ensure survival under starvation
      conditions.

PMID- 30186275
TI  - Nano-Sized and Filterable Bacteria and Archaea: Biodiversity and Function.
AB  - Nano-sized and filterable microorganisms are thought to represent the smallest
      living organisms on earth and are characterized by their small size (50-400 nm)
      and their ability to physically pass through <0.45 MUm pore size filters. They
      appear to be ubiquitous in the biosphere and are present at high abundance across
      a diverse range of habitats including oceans, rivers, soils, and subterranean
      bedrock. Small-sized organisms are detected by culture-independent and culture
      dependent approaches, with most remaining uncultured and uncharacterized at both
      metabolic and taxonomic levels. Consequently, their significance in ecological
      roles remain largely unknown. Successful isolation, however, has been achieved
      for some species (e.g., Nanoarchaeum equitans and "Candidatus Pelagibacter
      ubique"). In many instances, small-sized organisms exhibit a significant genome
      reduction and loss of essential metabolic pathways required for a free-living
      lifestyle, making their survival reliant on other microbial community members. In
      these cases, the nano-sized prokaryotes can only be co-cultured with their
      'hosts.' This paper analyses the recent data on small-sized microorganisms in the
      context of their taxonomic diversity and potential functions in the environment.

PMID- 30186278
TI  - Use of a Potential Probiotic, Lactobacillus casei L4, in the Preparation of
      Fermented Coconut Water Beverage.
AB  - Coconut water (CW) is a clear, nutritive liquid found as the coconut endosperm of
      green coconuts such as Cocos nucifera L., and its widespread consumption owes to
      its unique composition of sugars, minerals, vitamins, enzymes, and hormones.
      Probiotic fermentation of CW may facilitate the development of an improved
      functional beverage with probiotic benefits; therefore, we aimed to produce a
      fermented CW beverage using the potential probiotic Lactobacillus casei L4. CW
      was fermented with L. casei L4 for 48 h at 35 degrees C, and the pH, organic acid
      production rate, antioxidant activity, antibacterial activity, sugar, mineral,
      vitamin B12 levels, and total viable bacteria counts were investigated at 24 and
      48 h. We demonstrated that the fermentation of CW with probiotic lactobacilli
      increased the cell viability count. Vitamin B12 production was highest in the
      extracellular environment at 48 h (11.47 MUg/mL), while the total phenolic
      content was significantly (p < 0.05) higher in the fermented CW at 48 h (72.1
      MUg/mL gallic acid equivalents) than observed with the other investigated groups
      or time points. The fermented materials exhibited the highest 1,1-diphenyl-2
      picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)
      (ABTS) radical-scavenging activities at 48 h (58.4 and 69.2%, respectively). The
      levels of most minerals remained unchanged in the fermented CW, except for
      calcium, manganese, phosphorus, and sodium. Furthermore, the culture supernatant
      from fermented CW inhibited the growth of foodborne pathogens such as Bacillus
      cereus, Listeria monocytogenes, Staphylococcus aureus, and Salmonella typhi,
      although the degree of inhibition varied between the species. Moreover, adding
      15% honey and artificial coconut flavor to the fermented CW resulted in a better
      tasting product, as demonstrated by a sensory-evaluation test. The obtained
      results indicated that the CW product fermented by L. casei L4 may be used as a
      novel functional beverage containing both electrolytes and probiotics, and can
      serve as a good vehicle for preparing a wider range of novel products.

PMID- 30186277
TI  - Identification and Classification for the Lactobacillus casei Group.
AB  - Lactobacillus casei, Lactobacillus paracasei, and Lactobacillus rhamnosus are
      phenotypically and genotypically closely related, and together comprise the L.
      casei group. Although the strains of this group are commercially valuable as
      probiotics, the taxonomic status and nomenclature of the L. casei group have long
      been contentious because of the difficulties in identifying these three species
      by using the most frequently used genotypic methodology of 16S rRNA gene
      sequencing. Long used as the gold standard for species classification, DNA-DNA
      hybridization is laborious, requires expert skills, and is difficult to use
      routinely in laboratories. Currently, genome-based comparisons, including average
      nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH), are commonly
      applied to bacterial taxonomy as alternatives to the gold standard method for the
      demarcating phylogenetic relationships. To establish quick and accurate methods
      for identifying strains in the L. casei group at the species and subspecies
      levels, we developed species- and subspecies-specific identification methods
      based on housekeeping gene sequences and whole-cell matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) spectral
      pattern analysis. By phylogenetic analysis based on concatenated housekeeping
      gene sequences (dnaJ, dnaK, mutL, pheS, and yycH), 53 strains were separated into
      four clusters corresponding to the four species: L. casei, L. paracasei and L.
      rhamnosus, and Lactobacillus chiayiensis sp. nov. A multiplex minisequencing
      assay using single nucleotide polymorphism (SNP)-specific primers based on the
      dnaK gene sequences and species-specific primers based on the mutL gene sequences
      provided high resolution that enabled the strains at the species level to be
      identified as L. casei, L. paracasei, and L. rhamnosus. By MALDI-TOF MS analysis
      coupled with an internal database and ClinProTools software, species- and
      subspecies-level L. casei group strains were identified based on reliable scores
      and species- and subspecies-specific MS peaks. The L. paracasei strains were
      distinguished clearly at the subspecies level based on subspecies-specific MS
      peaks. This article describes the rapid and accurate methods used for
      identification and classification of strains in the L. casei group based on
      housekeeping gene sequences and MALDI-TOF MS analysis as well as the novel
      speciation of this group including L. chiayiensis sp. nov. and 'Lactobacillus
      zeae' by genome-based methods.

PMID- 30186279
TI  - The Effect of Co-infection of Food-Borne Pathogenic Bacteria on the Progression
      of Campylobacter jejuni Infection in Mice.
AB  - Campylobacter is a well-known food-borne pathogen that causes human
      gastroenteritis. Food products that contain Campylobacter may also be
      contaminated by other pathogens, however, whether this multiple contamination
      leads to more severe infection remains unclear. In this study, mice were gavaged
      with Campylobacter jejuni and other food-borne pathogenic bacteria to mimic a
      multiple infection. It was demonstrated that the C. jejuni load was elevated when
      the mice were co-infected with C. jejuni and Salmonella typhimurium, and the
      campylobacteriosis that followed was also enhanced, with features of decreased
      body weight, heavier bloody stools and more pronounced inflammatory changes to
      the colon. In addition, infection with C. jejuni was also promoted by co
      infection with entero-invasive Escherichia coli but unaffected over time. In
      contrast to S. typhimurium and entero-invasive E. coli, co-infection by Listeria
      monocytogenes showed little effect on C. jejuni infection and even hindered its
      progress. In addition, the intestinal microecology was also affected by co
      infection of C. jejuni with other pathogens, with an increased relative abundance
      of unclassified Enterobacteriaceae, decreased levels of butyric acid and changes
      in the abundance of several genera of gut microbe, which suggests that some food
      borne pathogenic bacteria might affect the progression of C. jejuni infection in
      mice by influencing the composition of the gut microbiota and the resulting
      changes in SCFA levels. Collectively, our findings suggest that co-infection of
      Campylobacter with other pathogenic bacteria can impact on the progression of
      infection by C. jejuni in mice, which may also have implication for the etiology
      of Campylobacter on human health.

PMID- 30186280
TI  - Sulfate-Reducing Bacteria as an Effective Tool for Sustainable Acid Mine
      Bioremediation.
AB  - Mining industries produce vast waste streams that pose severe environmental
      pollution challenge. Conventional techniques of treatment are usually inefficient
      and unsustainable. Biological technique employing the use of microorganisms is a
      competitive alternative to treat mine wastes and recover toxic heavy metals.
      Microorganisms are used to detoxify, extract or sequester pollutants from mine
      waste. Sulfate-reducing microorganisms play a vital role in the control and
      treatment of mine waste, generating alkalinity and neutralizing the acidic waste.
      The design of engineered sulfate-reducing bacteria (SRB) consortia will be an
      effective tool in optimizing degradation of acid mine tailings waste in
      industrial processes. The understanding of the complex functions of SRB consortia
      vis-a-vis the metabolic and physiological properties in industrial applications
      and their roles in interspecies interactions are discussed.

PMID- 30186284
TI  - Super-Resolution Correlative Light and Electron Microscopy (SR-CLEM) Reveals
      Novel Ultrastructural Insights Into Dendritic Cell Podosomes.
AB  - Podosomes are multimolecular cytoskeletal structures that coordinate the
      migration of tissue-resident dendritic cells (DCs). They consist of a protrusive
      actin-rich core and an adhesive integrin-rich ring that contains adaptor proteins
      such as vinculin and zyxin. Individual podosomes are typically interconnected by
      a dense network of actin filaments giving rise to large podosome clusters. The
      actin density in podosome clusters complicates the analysis of podosomes by light
      microscopy alone. Here, we present an optimized procedure for performing super
      resolution correlative light and electron microscopy (SR-CLEM) to study the
      organization of multiple proteins with respect to actin in podosome clusters at
      the ventral plasma membrane of DCs. We demonstrate that our procedure is suited
      to correlate at least three colors in super-resolution Airyscan microscopy with
      scanning electron microscopy (SEM). Using this procedure, we first reveal an
      intriguing complexity in the organization of ventral and radiating actin
      filaments in clusters formed by DCs which was not properly detected before by
      light microscopy alone. Next, we demonstrate a differential organization of
      vinculin and zyxin with respect to the actin filaments at podosomes. While
      vinculin mostly resides at sites where the actin filaments connect to the cell
      membrane, zyxin is primarily associated with filaments close to and on top of the
      core. Finally, we reveal a novel actin-based structure with SEM that connects
      closely associated podosome cores and which may be important for podosome
      topography sensing. Interestingly, these interpodosomal connections, in contrast
      to the radiating and ventral actin filaments appear to be insensitive to
      inhibition of actin polymerization suggesting that these pools of actin are not
      dynamically coupled. Together, our work demonstrates the power of correlating
      different imaging modalities for studying multimolecular cellular structures and
      could potentially be further exploited to study processes at the ventral plasma
      membrane of immune cells such as clathrin-mediated endocytosis or immune synapse
      formation.

PMID- 30186285
TI  - The Combined Use of Melatonin and an Indoleamine 2,3-Dioxygenase-1 Inhibitor
      Enhances Vaccine-Induced Protective Cellular Immunity to HPV16-Associated Tumors.
AB  - Immunotherapy has become an important ally in the fight against distinct types of
      cancer. However, the metabolic plasticity of the tumor environment frequently
      influences the efficacy of therapeutic procedures, including those based on
      immunological tools. In this scenario, immunometabolic adjuvants arise as an
      alternative toward the development of more efficient cancer therapies. Here we
      demonstrated that the combination of melatonin, a neuroimmunomodulator molecule,
      and an indoleamine 2,3-dioxygenase (IDO) inhibitor (1-methyl-DL-tryptophan, DL
      1MT) improves the efficacy of an immunotherapy (gDE7) targeting human
      papillomavirus (HPV)-associated tumors. Melatonin or IDO inhibitors (D-1MT and DL
      1MT) directly reduced proliferation, migration, adhesion and viability of a tumor
      cell line (TC-1), capable to express the HPV-16 E6 and E7 oncoproteins, but could
      not confer in vivo antitumor protection effects. Nonetheless, combination of gDE7
      with melatonin or D-1MT or DL-1MT enhanced the antitumor protective immunity of
      gDE7-based vaccine in mice. Notably, expression of IDO1 in stromal cells and/or
      immune cells, but not in tumor cells, inhibited the antitumor effects of the
      gDE7, as demonstrated in IDO1-deficient mice. Finally, co-administration of gDE7,
      melatonin and DL-1MT further improved the protective antitumor effects and the
      numbers of circulating E7-specific CD8+ T cells in mice previously transplanted
      with TC-1 cells. The unprecedented combination of melatonin and IDO inhibitors,
      as immunometabolic adjuvants, thus, represents a new and promising alternative
      for improving the efficacy of immunotherapeutic treatments of HPV-associated
      tumors.

PMID- 30186283
TI  - Calcium Oxalate Differentiates Human Monocytes Into Inflammatory M1 Macrophages.
AB  - Purpose: A number of hyperoxaluric states have been associated with calcium
      oxalate (CaOx) deposits in the kidneys. In animal models of stone disease, these
      crystals interact with circulating monocytes that have migrated into the kidney
      as part of innate immunity. Similarly, macrophages surround CaOx crystals in
      kidneys of patients excreting high levels of oxalate. We investigate the effect
      of this exposure and subsequent human immunological response in vitro. Materials
      and methods: Primary human monocytes were collected from healthy donors and
      exposed to CaOx, potassium oxalate, and zinc oxalate (ZnOx). Cytokine production
      was measured with a multiplex ELISA. Quantitative reverse transcription
      polymerase chain reaction was done to validate the mRNA profile expression. M1
      macrophage phenotype was confirmed with immunofluorescence microscopy. Results:
      Both primary monocytes and THP-1 cells, a human monocytic cell line, respond
      strongly to CaOx crystals in a dose-dependent manner producing TNF-alpha, IL
      1beta, IL-8, and IL-10 transcripts. Exposure to CaOx followed by 1 h with LPS had
      an additive effect for cytokine production compared to LPS alone, however, LPS
      followed by CaOx led to significant decrease in cytokine production. Supernatants
      taken from monocytes were previously exposed to CaOx crystals enhance M2
      macrophage crystal phagocytosis. CaOx, but not potassium or ZnOx, promotes
      monocyte differentiation into inflammatory M1-like macrophages. Conclusion: In
      our in vitro experiment, human monocytes were activated by CaOx and produced
      inflammatory cytokines. Monocytes recognized CaOx crystals through a specific
      mechanism that can enhance or decrease the innate immune response to LPS. CaOx
      promoted M1 macrophage development. These results suggest that monocytes have an
      important role promoting CaOx-induced inflammation.

PMID- 30186282
TI  - Human Bone Marrow-Resident Natural Killer Cells Have a Unique Transcriptional
      Profile and Resemble Resident Memory CD8+ T Cells.
AB  - Human lymphoid tissues harbor, in addition to CD56bright and CD56dim natural
      killer (NK) cells, a third NK cell population: CD69+CXCR6+ lymphoid tissue (lt)NK
      cells. The function and development of ltNK cells remain poorly understood. In
      this study, we performed RNA sequencing on the three NK cell populations derived
      from bone marrow (BM) and blood. In ltNK cells, 1,353 genes were differentially
      expressed compared to circulating NK cells. Several molecules involved in
      migration were downregulated in ltNK cells: S1PR1, SELPLG and CD62L. By flow
      cytometry we confirmed that the expression profile of adhesion molecules (CD49e-,
      CD29low, CD81high, CD62L-, CD11c-) and transcription factors (Eomeshigh, Tbetlow)
      of ltNK cells differed from their circulating counterparts. LtNK cells were
      characterized by enhanced expression of inhibitory receptors TIGIT and CD96 and
      low expression of DNAM1 and cytolytic molecules (GZMB, GZMH, GNLY). Their
      proliferative capacity was reduced compared to the circulating NK cells. By
      performing gene set enrichment analysis, we identified DUSP6 and EGR2 as
      potential regulators of the ltNK cell transcriptome. Remarkably, comparison of
      the ltNK cell transcriptome to the published human spleen-resident memory CD8+ T
      (Trm) cell transcriptome revealed an overlapping gene signature. Moreover, the
      phenotypic profile of ltNK cells resembled that of CD8+ Trm cells in BM.
      Together, we provide transcriptional and phenotypic data that clearly distinguish
      ltNK cells from both the CD56bright and CD56dim NK cells and substantiate the
      view that ltNK cells are tissue-resident cells, which are functionally restrained
      in killing and have low proliferative activity.

PMID- 30186287
TI  - The Potential Therapeutic Role of miR-223 in Bovine Endometritis by Targeting the
      NLRP3 Inflammasome.
AB  - Bovine endometritis affects milk production and reproductive performance in dairy
      cows and causes serious economic loss. The underlying molecular mechanisms or
      signaling pathways of bovine endometritis remain unclear. In this study, we
      attempted to determine the expression mechanism of mir-223 in endometritis of
      dairy cows and evaluate its potential therapeutic value. We first confirmed that
      there was an increased level of miR-223 in endometritis, and then, an LPS-induced
      bovine endometrial epithelial cell (BEND) line was used to mimic the inflammatory
      model in vitro. Our data showed that activation of NF-kappaB promoted the
      transcription of miR-223, thus inhibiting activation of the inflammatory mediator
      NLRP3 and its mediation of IL-1beta production to protect against inflammatory
      damage. Meanwhile, in vivo studies showed that inhibition of mir-223 resulted in
      an enhanced pathology of mice during LPS-induced endometritis, while
      overexpression of mir-223 attenuated the inflammatory conditions in the uterus.
      In summary, our study highlights that miR-223 serves both to constrain the level
      of NLRP3 activation and to act as a protective factor in the inflammatory
      response and thus provides a future novel therapeutic modality for active flares
      in cow endometritis and other inflammatory diseases.

PMID- 30186286
TI  - Innate Immune Memory in Invertebrate Metazoans: A Critical Appraisal.
AB  - The ability of developing immunological memory, a characteristic feature of
      adaptive immunity, is clearly present also in innate immune responses. In fact,
      it is well known that plants and invertebrate metazoans, which only have an
      innate immune system, can mount a faster and more effective response upon re
      exposure to a stimulus. Evidence of immune memory in invertebrates comes from
      studies in infection immunity, natural transplantation immunity, individual, and
      transgenerational immune priming. These studies strongly suggest that environment
      and lifestyle take part in the development of immunological memory. However, in
      several instances the formal correlation between the phenomenon of immune memory
      and molecular and functional immune parameters is still missing. In this review,
      we have critically examined the cellular and humoral aspects of the invertebrate
      immune memory responses. In particular, we have focused our analysis on studies
      that have addressed immune memory in the most restrictive meaning of the term,
      i.e., the response to a challenge of a quiescent immune system that has been
      primed in the past. These studies highlight the central role of an increase in
      the number of immune cells and of their epigenetic re-programming in the
      establishment of sensu stricto immune memory in invertebrates.

PMID- 30186288
TI  - Repositioning of the beta-Blocker Carvedilol as a Novel Autophagy Inducer That
      Inhibits the NLRP3 Inflammasome.
AB  - The NLRP3 inflammasome is a multiprotein complex that plays a key role in the
      innate immune system, and aberrant activation of this complex is involved in the
      pathogenesis of inflammatory diseases. Carvedilol (CVL) is an alpha-, beta
      blocker used to treat high blood pressure and congestive heart failure; however,
      some benefits beyond decreased blood pressure were observed clinically,
      suggesting the potential anti-inflammatory activity of CVL. In this report, the
      inhibitory potential of CVL toward the NLRP3 inflammasome and the possible
      underlying molecular mechanisms were studied. Our results showed that CVL
      attenuated NLRP3 inflammasome activation and pyroptosis in mouse macrophages,
      without affecting activation of the AIM2, NLRC4 and non-canonical inflammasomes.
      Mechanistic analysis revealed that CVL prevented lysosomal and mitochondrial
      damage and reduced ASC oligomerization. Additionally, CVL caused autophagic
      induction through a Sirt1-dependent pathway, which inhibited the NLRP3
      inflammasome. In the in vivo mouse model of NLRP3-associated peritonitis, oral
      administration of CVL reduced (1) peritoneal recruitment of neutrophils; (2) the
      levels of IL-1beta, IL-18, active caspase-1, ASC, IL-6, TNF-alpha, MCP-1, and
      CXCL1 in the lavage fluids; and (3) the levels of NLRP3 and HO-1 in the
      peritoneal cells. Our results indicated that CVL is a novel autophagy inducer
      that inhibits the NLRP3 inflammasome and can be repositioned for ameliorating
      NLRP3-associated complications.

PMID- 30186289
TI  - Identification of Cucumber mosaic resistance 2 (cmr2) That Confers Resistance to
      a New Cucumber mosaic virus Isolate P1 (CMV-P1) in Pepper (Capsicum spp.).
AB  - Cucumber mosaic virus (CMV) is one of the most devastating phytopathogens of
      Capsicum. The single dominant resistance gene, Cucumber mosaic resistant 1
      (Cmr1), that confers resistance to the CMV isolate P0 has been overcome by a new
      isolate (CMV-P1) after being deployed in pepper (Capsicum annuum) breeding for
      over 20 years. A recently identified Indian C. annuum cultivar, "Lam32," displays
      resistance to CMV-P1. In this study, we show that the resistance in "Lam32" is
      controlled by a single recessive gene, CMV resistance gene 2 (cmr2). We found
      that cmr2 conferred resistance to CMV strains including CMV-Korean, CMV-Fny, and
      CMV-P1, indicating that cmr2 provides a broad-spectrum type of resistance. We
      utilized two molecular mapping approaches to determine the chromosomal location
      of cmr2. Bulked segregant analysis (BSA) using amplified fragment-length
      polymorphism (AFLP) (BSA-AFLP) revealed one marker, cmvAFLP, located 16 cM from
      cmr2. BSA using the Affymetrix pepper array (BSA-Affy) identified a single
      nucleotide polymorphism (SNP) marker (Affy4) located 2.3 cM from cmr2 on
      chromosome 8. We further screened a pepper germplasm collection of 4,197
      accessions for additional CMV-P1 resistance sources and found that some
      accessions contained equivalent levels of resistance to that of "Lam32."
      Inheritance and allelism tests demonstrated that all the resistance sources
      examined contained cmr2. Our result thus provide genetic and molecular evidence
      that cmr2 is a single recessive gene that confers to pepper an unprecedented
      resistance to the dangerous new isolate CMV-P1 that had overcome Cmr1.

PMID- 30186290
TI  - Enhancement of Low pH Stress Tolerance in Anthocyanin-Enriched Transgenic Petunia
      Overexpressing RsMYB1 Gene.
AB  - We investigated whether the presence of anthocyanins in plants could contribute
      to low pH stress tolerance using anthocyanin-enriched transgenic petunia lines
      (PM2, PM6, and PM8) expressing RsMYB1 and wild-type (WT) plants. We examined
      several physiological and biochemical factors and the transcript levels of genes
      involved in abiotic stress tolerance. A reduction in plant growth, including
      plant height and fresh weight, was observed when plants (PM2, PM6, PM8, and WT)
      were exposed to low pH (pH 3.0) conditions compared to growth under normal (pH
      5.8) conditions. A small reduction in the growth of PM6 was observed, followed by
      that in PM2, PM8, and WT, reflecting the anthocyanin levels in the plants (PM6 >
      PM2 and PM8 > WT). An analysis of physiological and biochemical factors also
      supports the degree of low pH tolerance in the plants (PM6 > PM2 and PM8 > WT).
      In addition, an enhanced expression of the genes [superoxide dismutase (SOD),
      catalase (CAT), peroxidase (POX), osmotin, and vacuolar H+-ATPase (V-ATPase)] was
      observed in the transgenic lines (PM2, PM6, and PM8). The resultant of the
      enhanced transcript levels of the genes could promote antioxidant activities,
      proline content, and pH homeostasis involved in the mechanisms underlying abiotic
      stress tolerance in plants. These results suggest that anthocyanin-enriched
      plants overexpressing RsMYB1 enhances low pH stress tolerance by elevating the
      transcript levels of the relevant genes.

PMID- 30186292
TI  - Genome-Wide Association Studies for Five Forage Quality-Related Traits in Sorghum
      (Sorghum bicolor L.).
AB  - Understanding the genetic function of the forage quality-related traits,
      including crude protein (CP), neutral detergent fiber (NDF), acid detergent fiber
      (ADF), hemicellulose (HC), and cellulose (CL) contents, is essential for the
      identification of forage quality genes and selection of effective molecular
      markers in sorghum. In this study, we genotyped 245 sorghum accessions by 85,585
      single-nucleotide polymorphisms (SNPs) and obtained the phenotypic data from four
      environments. The SNPs and phenotypic data were applied to multi-locus genome
      wide association studies (GWAS) with the mrMLM software. A total of 42 SNPs were
      identified to be associated with the five forage quality-related traits.
      Moreover, three and two quantitative trait nucleotides (QTNs) were simultaneously
      detected among them by three and two multi-locus methods, respectively. One QTN
      on chromosome 5 was found to be associated simultaneously with CP, NDF, and ADF.
      Furthermore, 3, 2, 2, 5, and 2 candidate genes were identified to be responsible
      for CP, NDF, ADF, HC, and CL contents, respectively. These results provided
      insightful information of the forage quality-related traits and would facilitate
      the genetic improvement of sorghum forage quality in the future.

PMID- 30186293
TI  - Genetic Diversity and Population Structure of the USDA Sweetpotato (Ipomoea
      batatas) Germplasm Collections Using GBSpoly.
AB  - Sweetpotato (Ipomoea batatas) plays a critical role in food security and is the
      most important root crop worldwide following potatoes and cassava. In the United
      States (US), it is valued at over $700 million USD. There are two sweetpotato
      germplasm collections (Plant Genetic Resources Conservation Unit and US Vegetable
      Laboratory) maintained by the USDA, ARS for sweetpotato crop improvement. To
      date, no genome-wide assessment of genetic diversity within these collections has
      been reported in the published literature. In our study, population structure and
      genetic diversity of 417 USDA sweetpotato accessions originating from 8 broad
      geographical regions (Africa, Australia, Caribbean, Central America, Far East,
      North America, Pacific Islands, and South America) were determined using single
      nucleotide polymorphisms (SNPs) identified with a genotyping-by-sequencing (GBS)
      protocol, GBSpoly, optimized for highly heterozygous and polyploid species.
      Population structure using Bayesian clustering analyses (STRUCTURE) with 32,784
      segregating SNPs grouped the accessions into four genetic groups and indicated a
      high degree of mixed ancestry. A neighbor-joining cladogram and principal
      components analysis based on a pairwise genetic distance matrix of the accessions
      supported the population structure analysis. Pairwise FST values between broad
      geographical regions based on the origin of accessions ranged from 0.017 (Far
      East - Pacific Islands) to 0.110 (Australia - South America) and supported the
      clustering of accessions based on genetic distance. The markers developed for use
      with this collection of accessions provide an important genomic resource for the
      sweetpotato community, and contribute to our understanding of the genetic
      diversity present within the US sweetpotato collection and the species.

PMID- 30186291
TI  - Is Nitrogen a Key Determinant of Water Transport and Photosynthesis in Higher
      Plants Upon Drought Stress?
AB  - Drought stress is a major global issue limiting agricultural productivity. Plants
      respond to drought stress through a series of physiological, cellular, and
      molecular changes for survival. The regulation of water transport and
      photosynthesis play crucial roles in improving plants' drought tolerance.
      Nitrogen (N, ammonium and nitrate) is an essential macronutrient for plants, and
      it can affect many aspects of plant growth and metabolic pathways, including
      water relations and photosynthesis. This review focuses on how drought stress
      affects water transport and photosynthesis, including the regulation of hydraulic
      conductance, aquaporin expression, and photosynthesis. It also discusses the
      cross talk between N, water transport, and drought stress in higher plants.

PMID- 30186294
TI  - Species-Associated Differences in the Below-Ground Microbiomes of Wild and
      Domesticated Setaria.
AB  - The rhizosphere microbiome is known to play a crucial role in promoting plant
      growth, partly by countering soil-borne phytoparasites and by improving nutrient
      uptake. The abundance and composition of the rhizosphere and root-associated
      microbiota are influenced by several factors, including plant species and
      genotype. We hypothesize that crop domestication might influence the composition
      and diversity of plant-associated microbiomes. We tested the contribution of
      domestication to the bacterial and archaeal root and soil composition associated
      with six genotypes of domesticated Setaria italica and four genotypes of its wild
      ancestor, S. viridis. The bacterial microbiome in the rhizoplane and root
      endophyte compartments, and the archaea in the endophyte compartment, showed
      major composition differences. For instance, members of the Betaproteobacteria
      and Firmicutes were overrepresented in S. italica root samples compared to S.
      viridis. Metagenomic analysis of samples that contained both root surface-bound
      (rhizoplane) and inside-root (endophytic) bacteria defined two unique microbial
      communities only associated with S. italica roots and one only associated with S.
      viridis roots. Root endophytic bacteria were found in six discernible
      communities, of which four were primarily on S. italica and two primarily on S.
      viridis. Among archaea, Methanobacteria, and Methanomicrobia exhibited species
      associated differences in the rhizosphere and root compartments, but most
      detected archaea were not classified more specifically than at the level of
      phylum. These results indicate a host genetic contribution to the microbial
      composition in Setaria, and suggest that domestication has selected for specific
      associations in the root and in the rhizosphere.

PMID- 30186295
TI  - Iron and Zinc in the Embryo and Endosperm of Rice (Oryza sativa L.) Seeds in
      Contrasting 2'-Deoxymugineic Acid/Nicotianamine Scenarios.
AB  - Iron and Zn deficiencies are worldwide nutritional disorders that can be
      alleviated by increasing the metal concentration of rice (Oryza sativa L.) grains
      via bio-fortification approaches. The overproduction of the metal chelator
      nicotianamine (NA) is among the most effective ones, but it is still unclear
      whether this is due to the enrichment in NA itself and/or the concomitant
      enrichment in the NA derivative 2'-deoxymugineic acid (DMA). The endosperm is the
      most commonly consumed portion of the rice grain and mediates the transfer of
      nutrients from vegetative tissues to the metal rich embryo. The impact of
      contrasting levels of DMA and NA on the metal distribution in the embryo and
      endosperm of rice seeds has been assessed using wild-type rice and six different
      transgenic lines overexpressing nicotianamine synthase (OsNAS1) and/or barley
      nicotianamine amino transferase (HvNAATb). These transgenic lines outlined three
      different DMA/NA scenarios: (i) in a first scenario, an enhanced NA level (via
      overexpression of OsNAS1) would not be fully depleted because of a limited
      capacity to use NA for DMA synthesis (lack of -or low- expression of HvNAATb),
      and results in consistent enrichments in NA, DMA, Fe and Zn in the endosperm and
      NA, DMA and Fe in the embryo; (ii) in a second scenario, an enhanced NA level
      (via overexpression of OsNAS1) would be depleted by an enhanced capacity to use
      NA for DMA synthesis (via expression of HvNAATb), and results in enrichments only
      for DMA and Fe, both in the endosperm and embryo, and (iii) in a third scenario,
      the lack of sufficient NA replenishment would limit DMA synthesis, in spite of
      the enhanced capacity to use NA for this purpose (via expression of HvNAATb), and
      results in decreases in NA, variable changes in DMA and moderate decreases in Fe
      in the embryo and endosperm. Also, quantitative LA-ICP-MS metal map images of the
      embryo structures show that the first and second scenarios altered local
      distributions of Fe, and to a lesser extent of Zn. The roles of DMA/NA levels in
      the transport of Fe and Zn within the embryo are thoroughly discussed.

PMID- 30186296
TI  - Nuclear Speckle RNA Binding Proteins Remodel Alternative Splicing and the Non
      coding Arabidopsis Transcriptome to Regulate a Cross-Talk Between Auxin and
      Immune Responses.
AB  - Nuclear speckle RNA binding proteins (NSRs) act as regulators of alternative
      splicing (AS) and auxin-regulated developmental processes such as lateral root
      formation in Arabidopsis thaliana. These proteins were shown to interact with
      specific alternatively spliced mRNA targets and at least with one structured
      lncRNA, named Alternative Splicing Competitor RNA. Here, we used genome-wide
      analysis of RNAseq to monitor the NSR global role on multiple tiers of gene
      expression, including RNA processing and AS. NSRs affect AS of 100s of genes as
      well as the abundance of lncRNAs particularly in response to auxin. Among them,
      the FPA floral regulator displayed alternative polyadenylation and differential
      expression of antisense COOLAIR lncRNAs in nsra/b mutants. This may explains the
      early flowering phenotype observed in nsra and nsra/b mutants. GO enrichment
      analysis of affected lines revealed a novel link of NSRs with the immune response
      pathway. A RIP-seq approach on an NSRa fusion protein in mutant background
      identified that lncRNAs are privileged direct targets of NSRs in addition to
      specific AS mRNAs. The interplay of lncRNAs and AS mRNAs in NSR-containing
      complexes may control the crosstalk between auxin and the immune response
      pathway.

PMID- 30186298
TI  - Generalist and Specialist Mite Herbivores Induce Similar Defense Responses in
      Maize and Barley but Differ in Susceptibility to Benzoxazinoids.
AB  - While substantial progress has been made in understanding defense responses of
      cereals to insect herbivores, comparatively little is known about responses to
      feeding by spider mites. Nevertheless, several spider mite species, including the
      generalist Tetranychus urticae and the grass specialist Oligonychus pratensis,
      cause damage on cereals such as maize and wheat, especially during drought
      stress. To understand defense responses of cereals to spider mites, we
      characterized the transcriptomic responses of maize and barley to herbivory by
      both mite species, and included a wounding control against which modulation of
      defenses could be tested. T. urticae and O. pratensis induced highly correlated
      changes in gene expression on both maize and barley. Within 2 h, hundreds of
      genes were upregulated, and thousands of genes were up- or downregulated after 24
      h. In general, expression changes were similar to those induced by wounding,
      including for genes associated with jasmonic acid biosynthesis and signaling.
      Many genes encoding proteins involved in direct defenses, or those required for
      herbivore-induced plant volatiles, were strongly upregulated in response to mite
      herbivory. Further, biosynthesis genes for benzoxazinoids, which are specialized
      compounds of Poaceae with known roles in deterring insect herbivores, were
      induced in maize. Compared to chewing insects, spider mites are cell content
      feeders and cause grossly different patterns of tissue damage. Nonetheless, the
      gene expression responses of maize to both mite herbivores, including for
      phytohormone signaling pathways and for the synthesis of the benzoxazinoid 2
      hydroxy-4,7-dimethoxy-1,4-benzoxazin-3-one glucoside, a known defensive
      metabolite against caterpillars, resembled those reported for a generalist
      chewing insect, Spodoptera exigua. On maize plants harboring mutations in several
      benzoxazinoid biosynthesis genes, T. urticae performance dramatically increased
      compared to wild-type plants. In contrast, no difference in performance was
      observed between mutant and wild-type plants for the specialist O. pratensis.
      Collectively, our data provide little evidence that maize and barley defense
      responses differentiate herbivory between T. urticae and O. pratensis. Further,
      our work suggests that the likely route to specialization for O. pratensis
      involved the evolution of a robust mechanism to cope with the benzoxazinoid
      defenses of its cereal hosts.

PMID- 30186297
TI  - New Insights Into Wall Polysaccharide O-Acetylation.
AB  - The extracellular matrix of plants, algae, bacteria, fungi, and some archaea
      consist of a semipermeable composite containing polysaccharides. Many of these
      polysaccharides are O-acetylated imparting important physiochemical properties to
      the polymers. The position and degree of O-acetylation is genetically determined
      and varies between organisms, cell types, and developmental stages. Despite the
      importance of wall polysaccharide O-acetylation, only recently progress has been
      made to elucidate the molecular mechanism of O-acetylation. In plants, three
      protein families are involved in the transfer of the acetyl substituents to the
      various polysaccharides. In other organisms, this mechanism seems to be
      conserved, although the number of required components varies. In this review, we
      provide an update on the latest advances on plant polysaccharide O-acetylation
      and related information from other wall polysaccharide O-acetylating organisms
      such as bacteria and fungi. The biotechnological impact of understanding wall
      polysaccharide O-acetylation ranges from the design of novel drugs against human
      pathogenic bacteria to the development of improved lignocellulosic feedstocks for
      biofuel production.

PMID- 30186299
TI  - Mapping and Functional Analysis of a Maize Silkless Mutant sk-A7110.
AB  - The maize (Zea mays) stigma, which is commonly known as silk, is indispensable
      for reproduction and thus for grain yield. Here, we isolated a spontaneous mutant
      sk-A7110, which completely lacks silk; scanning electron microscopy showed that
      the sk-A7110 pistils degenerated during late floret differentiation. Genetic
      analysis confirmed that this trait was controlled by a recessive nuclear gene and
      sk-A7110 was mapped to a 74.13-kb region on chromosome 2 between the simple
      sequence repeat markers LA714 and L277. Sequence analysis of candidate genes in
      this interval identified a single-nucleotide insertion at position 569 downstream
      of the transcriptional start site in Zm00001d002970, which encodes a UDP
      glycosyltransferase; this insertion produces a frameshift and premature
      translational termination. RNA-sequencing analysis of young ears identified 258
      differentially expressed genes (DEGs) between sk-A7110 and the wild type (WT),
      including 119 up- and 139 down-regulated genes. Interestingly, most DEGs related
      to jasmonic acid (JA) synthesis were up-regulated in the mutant compared to WT.
      Consistent with this, the JA and JA-Isoleucine (JA-Ile) contents were
      significantly higher in sk-A7110 ears than in WT. At the same time, RNA
      sequencing analysis of tassels showed that sk-A7110 could reduce the number of
      tassel branches in maize by down-regulating the expression of UB2 and UB3 genes.
      Our identification of the sk-A7110 mutant and the responsible gene will
      facilitate further studies on female infertility research or maize breeding.

PMID- 30186300
TI  - Root JA Induction Modifies Glucosinolate Profiles and Increases Subsequent
      Aboveground Resistance to Herbivore Attack in Cardamine hirsuta.
AB  - Alteration and induction of plant secondary metabolites after herbivore attack
      have been shown in almost all the studied plant species. Induction can be at the
      local site of damage, or systemic, such as from roots to shoots. In addition to
      immediate induction, previous herbivore bouts have been shown to "prime" the
      plants for a stronger and faster response only after a subsequent attack happens.
      Whereas several studies revealed a link between root herbivory and increased
      resistance against aboveground (AG) herbivory, the evidence of root defense
      priming against subsequent AG herbivory is currently lacking. To address this
      gap, we induced Cardamine hirsuta roots by applying jasmonic acid (JA), and,
      after a time lag, we subjected both control and JA-treated plants to AG herbivory
      by the generalist herbivore Spodoptera littoralis. We addressed the effect of
      root JA addition on AG herbivore resistance by measuring larval weight gain and
      tested the effect of root induction on abundance and composition of
      glucosinolates (GSLs) in shoots, prior, and after subsequent herbivory. We
      observed a strong positive effect of root induction on the resistance against AG
      herbivory. The overall abundance and identity of GSLs was globally affected by JA
      induction and by herbivore feeding, independently, and we found a significant
      correlation between larval growth and the shoot GSL profiles only after AG
      herbivory, 11 days after induction in roots. Contrary to expectations of priming,
      we observed that JA induction in roots altered the GSLs profile in the leaves
      that was maintained through time. This initial modification was sufficient to
      maintain a lower caterpillar weight gain, even 11 days post-root induction.
      Altogether, we show that prior root defense induction increases AG insect
      resistance by modifying and maintaining variation in GSL profiles during insect
      feeding.

PMID- 30186302
TI  - Protein Hydrolysate Stimulates Growth in Tomato Coupled With N-Dependent Gene
      Expression Involved in N Assimilation.
AB  - Plant-derived protein hydrolysates (PHs) have received increased attention in the
      last decade because of their potential to improve yield, nutritional quality as
      well as tolerance to abiotic stressors. The current study investigated the
      effects and the molecular mechanisms of a legume-derived PH under optimal and sub
      optimal nitrogen (N) concentrations (112 and 7 mg L-1, respectively) in tomato
      (Solanum lycopersicum L.). Growth and mineral composition of tomato plants
      treated with PHs by foliar spray or substrate drench were compared to untreated
      plants. In addition, the expression was determined of genes encoding ammonium and
      nitrate transporters and seven enzymes involved in N metabolism: nitrate
      reductase (NR), nitrite reductase (NiR), glutamine synthetase 1 (GS1), glutamine
      synthetase 2 (GS2), ferredoxin-dependent glutamate synthase (GLT), NADH-dependent
      glutamate synthase (GLS), and glutamate dehydrogenase (GDH). The root and total
      plant dry weight, SPAD index and leaf nitrogen content were higher by 21, 17, 7,
      and 6%, respectively, in plants treated by a substrate drench in comparison to
      untreated tomato plants, whereas foliar application of PH gave intermediate
      values. PH-treated plants grown with lower N availability showed reduced
      expression of NR and NiR as well as of nitrate and ammonium transporter
      transcripts in both leaf and root tissues in comparison with untreated plants;
      this was especially pronounced after application of PH by substrate drench.
      Conversely, the transcript level of an amino acid transporter gene was up
      regulated in comparison with untreated plants. At high N regime, the transcript
      levels of the ammonium and amino acid transporters and also NR, NiR, and GLT were
      significantly up-regulated in root after PH foliar and substrate drench
      applications compared with untreated plants. An up-regulation was also observed
      for GS1, GS2, and GDH transcripts in leaf after substrate drench. These results
      highlighted the potential benefits of using legume PH in vegetable production
      systems to increase growth and N-nutritional status of plants.

PMID- 30186301
TI  - Regulation of Plant Growth and Development: A Review From a Chromatin Remodeling
      Perspective.
AB  - In eukaryotes, genetic material is packaged into a dynamic but stable
      nucleoprotein structure called chromatin. Post-translational modification of
      chromatin domains affects the expression of underlying genes and subsequently the
      identity of cells by conveying epigenetic information from mother to daughter
      cells. SWI/SNF chromatin remodelers are ATP-dependent complexes that modulate
      core histone protein polypeptides, incorporate variant histone species and modify
      nucleotides in DNA strands within the nucleosome. The present review discusses
      the SWI/SNF chromatin remodeler family, its classification and recent
      advancements. We also address the involvement of SWI/SNF remodelers in regulating
      vital plant growth and development processes such as meristem establishment and
      maintenance, cell differentiation, organ initiation, flower morphogenesis and
      flowering time regulation. Moreover, the role of chromatin remodelers in key
      phytohormone signaling pathways is also reviewed. The information provided in
      this review may prompt further debate and investigations aimed at understanding
      plant-specific epigenetic regulation mediated by chromatin remodeling under
      continuously varying plant growth conditions and global climate change.

PMID- 30186303
TI  - Increased DHA Production in Seed Oil Using a Selective Lysophosphatidic Acid
      Acyltransferase.
AB  - Metabolic engineering of the omega-3 (omega3) long chain polyunsaturated fatty
      acid biosynthesis pathway has generated fish oil-like levels of pharmaceutically
      and nutritionally important docosahexaenoic acid (DHA) in plant seeds. However,
      the majority of DHA has been accumulated at the sn-1 and sn-3 positions of
      triacylglycerol (TAG) in these engineered seeds, leaving only a minor amount
      (~10%) at sn-2 position and indicating a strong discrimination (or, a very poor
      specificity) for DHA by seed lysophosphatidic acid acyltransferases (LPAATs),
      which mediate the acylation of sn-2 position of glycerol backbone. In order to
      increase the level of DHA at sn-2 position of TAG and to increase overall DHA
      level in seeds, we attempted to discover DHA-preferring LPAATs. Several LPAATs
      for acylation of the sn-2 position of the TAG glycerol backbone were investigated
      for substrate preference for DHA. In transiently expressing these LPAATs in
      Nicotiana benthamiana, a Mortierella alpina LPAAT had the highest substrate
      specificity for accumulating DHA onto oleoyl-lysophosphatidic acid (oleoyl-LPA),
      while the plant LPAATs tested showed lower preference for DHA. In a competition
      assay with a pool of four omega3 acyl-Coenzyme A (CoA) substrates involved in the
      DHA biosynthesis pathway, LPAATs from both M. alpina and Emiliania huxleyi showed
      a high preference for DHA-CoA acylation onto oleoyl-LPA. When docosahexaenoyl-LPA
      was used as the acyl receiver, M. alpina LPAAT also showed a high preference for
      DHA-CoA. Stable overexpression of M. alpina LPAAT in an Arabidopsis line that
      expressed the DHA biosynthesis pathway significantly increased both the total DHA
      levels and the distribution of DHA onto the sn-2 position of seed TAG. LC-MS
      analysis of the seed TAG species also confirmed that overexpression of M. alpina
      LPAAT increased di-DHA and tri-DHA TAGs, suggesting that the M. alpina LPAAT
      could enrich DHA at the TAG sn-2 position, leading to a metabolic engineering of
      oil seed for channeling DHA into the sn-2 position of TAG and to a higher DHA
      level.

PMID- 30186304
TI  - Antioxidant Metabolism, Photosystem II, and Fatty Acid Composition of Two Tall
      Fescue Genotypes With Different Heat Tolerance Under High Temperature Stress.
AB  - Tall fescue (Festuca arundinacea Schreb.) is a typical and widely used cool
      season turf grass. High temperature is a key factor that limits its utility. The
      objectives of this study were to investigate the behaviors of fatty acid
      composition and its gene expression patterns in heat-resistant genotype "TF71"
      and heat-sensitive genotype "TF133" exposed to heat stress (40/35 degrees C,
      14/10 h), and to broaden our comprehension about the relationship between heat
      tolerance and fatty acid function. The result showed that heat stress increased
      the malondialdehyde (MDA) content and relative electrolyte leakage (EL), but
      decreased the level of chlorophyll and the activity of superoxide dismutase (SOD)
      and peroxidase (POD) when compared to the controls, to a greater extent in
      "TF133." This result proved that "TF71" had superior high-temperature resistance.
      Furthermore, comparing the changes in the composition of fatty acid and the
      expression of the genes involved in its synthesis between the two different
      genotypes under heat stress, we found that heat stress increased the degree of
      unsaturation, UFA/SFA, and double bond index (DBI) in "TF71." Moreover,
      quantitative RT-PCR revealed that heat stress altered the expression of the genes
      involved in fatty acid synthesis, including ACAC, FabD, FabF, FabH, FabI, and
      FatA. According to these findings, we can speculate that increasing the
      unsaturation degree of fatty acid or controlling the equilibrium ratio of UFA/SFA
      might be closely associated with the improving of the heat resistance in tall
      fescue.

PMID- 30186305
TI  - Enhancing Quality of Fresh Vegetables Through Salinity Eustress and
      Biofortification Applications Facilitated by Soilless Cultivation.
AB  - Closed soilless cultivation systems (SCS) support high productivity and optimized
      year-round production of standardized quality. Efficiency and precision in
      modulating nutrient solution composition, in addition to controlling temperature,
      light, and atmospheric composition, renders protected SCS instrumental for
      augmenting organoleptic and bioactive components of quality. Effective
      application of eustress (positive stress), such as moderate salinity or
      nutritional stress, can elicit tailored plant responses involving the activation
      of physiological and molecular mechanisms and the strategic accumulation of
      bioactive compounds necessary for adaptation to suboptimal environments. For
      instance, it has been demonstrated that the application of salinity eustress
      increases non-structural carbohydrates and health-promoting phytochemicals such
      as lycopene, beta-carotene, vitamin C, and the overall phenolic content of tomato
      fruits. Salinity eustress can also reduce the concentration of anti-nutrient
      compounds such as nitrate due to antagonism between nitrate and chloride for the
      same anion channel. Furthermore, SCS can be instrumental for the biofortification
      of vegetables with micronutrients essential or beneficial to human health, such
      as iodine, iron, selenium, silicon, and zinc. Accurate control of microelement
      concentrations and constant exposure of roots to the fortified nutrient solution
      without soil interaction can maximize their uptake, translocation, and
      accumulation in the edible plant parts; however, biofortification remains highly
      dependent on microelement forms and concentrations present in the nutrient
      solution, the time of application and the accumulation capacity of the selected
      species. The present article provides an updated overview and future perspective
      on scientific advances in SCS aimed at enhancing the sensory and bioactive value
      of vegetables.

PMID- 30186306
TI  - Neurogranin and BACE1 in CSF as Potential Biomarkers Differentiating Depression
      with Cognitive Deficits from Early Alzheimer's Disease: A Pilot Study.
AB  - Background/Aims: Major depressive disorder (MDD) can cooccur with early
      Alzheimer's disease (AD) or may cause memory problems independently of AD.
      Previous studies have suggested that the AD-related cerebrospinal fluid (CSF)
      biomarkers tau and Abeta(1-42) could help discriminate between early AD and
      depression unrelated to AD. Moreover, the postsynaptic protein neurogranin and
      presynaptic BACE1 have increasingly gained attention as potential new AD
      biomarkers, but they have not yet been investigated concerning depression.
      Methods: Using ELISAs, we studied CSF neurogranin and BACE1 levels in patients
      with mild (n = 21) and moderate (n = 19) AD, as well as in MDD patients with (n =
      20) and without (n = 20) cognitive deficits. The clinical examinations included
      analyses of t-tau, Abeta(1-42), and Abeta(1-40), besides neuropsychological tests
      and cranial magnetic resonance imaging. Depressive symptom severity was assessed
      using the Geriatric Depression Scale (GDS). Results: Along with classic AD
      biomarkers, neurogranin and BACE1 CSF levels differed between moderate AD and MDD
      (p <= 0.01). MDD associated with cognitive deficits was distinguished from mild
      AD through the CSF neurogranin/BACE1 ratio (p < 0.05), which was strongly
      correlated with GDS scores (rho = -0.656; p < 0.01). Conclusion: The
      neurogranin/BACE1 ratio in CSF can distinguish between depression and AD among
      patients with similar cognitive deficits, along with the classic AD biomarkers.
      Further longitudinal studies are ongoing to identify which biomarkers have
      prognostic value.

PMID- 30186309
TI  - Editorial: Evolutionary Feedbacks Between Population Biology and Genome
      Architecture.

PMID- 30186308
TI  - A Novel Computational Method for the Identification of Potential miRNA-Disease
      Association Based on Symmetric Non-negative Matrix Factorization and Kronecker
      Regularized Least Square.
AB  - Increasing evidence has indicated that microRNAs (miRNAs) are associated with
      numerous human diseases. Studying the associations between miRNAs and diseases
      contributes to the exploration of effective diagnostic and treatment approaches
      for diseases. Unfortunately, the use of biological experiments to reveal the
      potential associations between miRNAs and diseases is time consuming and costly.
      Therefore, it is very necessary to use simple and efficient calculation models to
      predict potential disease-related miRNAs. Considering the limitations of other
      previous methods, we proposed a novel computational model of Symmetric
      Nonnegative Matrix Factorization for MiRNA-Disease Association prediction
      (SNMFMDA) to reveal the relation of miRNA-disease pairs. SNMFMDA could be applied
      to predict miRNAs associated with new diseases. Compared to the direct use of the
      integrated similarity in previous computational models, the integrated similarity
      need to be interpolated by symmetric non-negative matrix factorization (SymNMF)
      before application in SNMFMDA, and the relevant probability of disease-miRNA was
      obtained mainly through Kronecker regularized least square (KronRLS) method in
      our model. What's more, the AUC of global leave-one-out cross validation (LOOCV)
      reached 0.9007, and the AUC based on local LOOCV was 0.8426. Besides, the mean
      and the standard deviation of AUCs achieved 0.8830 and 0.0017 respectively in 5
      fold cross validation. All of the above results demonstrated the superior
      prediction performance of SNMFMDA. We also conducted three different case studies
      on Esophageal Neoplasms, Breast Neoplasms and Lung Neoplasms, and 49, 49, and 48
      of the top 50 of their predicted miRNAs respectively were confirmed by databases
      or related literatures. It could be expected that SNMFMDA would be a model with
      the ability to predict disease-related miRNAs efficiently and accurately.

PMID- 30186307
TI  - Assessment of Molecular Measures in Non-FXTAS Male Premutation Carriers.
AB  - Approximately 30-40% of male and 8-16% of female carriers of the Fragile X
      premutation will develop a neurodegenerative movement disorder characterized by
      intentional tremor, gait ataxia, autonomic dysfunction, cognitive decline, and
      Parkinsonism during their lifetime. At the molecular level, premutation carriers
      have increased expression levels of the FMR1 and the antisense FMR1 (ASFMR1)
      mRNAs. Both genes undergo alternative splicing giving rise to a number of
      different transcripts. Alteration in the alternative splicing process might be
      associated with FXTAS. In this study, we have investigated the correlation
      between objective measures of movement (balance and tremor using the CATSYS
      battery) and the expression of both the FMR1 and the ASFMR1 genes. In addition,
      we investigated whether their expression level and that of the ASFMR1 131 bp
      splice isoform could distinguish between premutation carriers with FXTAS and non
      FXTAS premutation carriers. Confirming previous findings, the expression levels
      of transcripts at the FMR1 locus positively correlated with the CGG repeat number
      and significantly differentiated the premutation carriers from the control
      groups. Furthermore, premutation carriers with and without FXTAS, showed a
      significant difference in the expression level of the ASFMR1 131 bp splice
      isoform when compared to age and gender matched controls. However, there was no
      significant difference in the ASFMR1 131 bp splice isoform expression level when
      comparing premutation carriers with and without FXTAS. Finally, our results
      indicate significant group differences in CATSYS dominant hand reaction time and
      postural sway with eyes closed in premutation carriers without FXTAS compared to
      controls. In addition, a significant inverse association between the tremor
      intensity and the expression level of ASFMR1 131 bp splice isoform in premutation
      carriers compared to controls, was observed, suggesting a potential role in the
      pathogenesis of FXTAS.

PMID- 30186281
TI  - Genome-Based Taxonomic Classification of the Phylum Actinobacteria.
AB  - The application of phylogenetic taxonomic procedures led to improvements in the
      classification of bacteria assigned to the phylum Actinobacteria but even so
      there remains a need to further clarify relationships within a taxon that
      encompasses organisms of agricultural, biotechnological, clinical, and ecological
      importance. Classification of the morphologically diverse bacteria belonging to
      this large phylum based on a limited number of features has proved to be
      difficult, not least when taxonomic decisions rested heavily on interpretation of
      poorly resolved 16S rRNA gene trees. Here, draft genome sequences of a large
      collection of actinobacterial type strains were used to infer phylogenetic trees
      from genome-scale data using principles drawn from phylogenetic systematics. The
      majority of taxa were found to be monophyletic but several orders, families, and
      genera, as well as many species and a few subspecies were shown to be in need of
      revision leading to proposals for the recognition of 2 orders, 10 families, and
      17 genera, as well as the transfer of over 100 species to other genera. In
      addition, emended descriptions are given for many species mainly involving the
      addition of data on genome size and DNA G+C content, the former can be considered
      to be a valuable taxonomic marker in actinobacterial systematics. Many of the
      incongruities detected when the results of the present study were compared with
      existing classifications had been recognized from 16S rRNA gene trees though
      whole-genome phylogenies proved to be much better resolved. The few significant
      incongruities found between 16S/23S rRNA and whole genome trees underline the
      pitfalls inherent in phylogenies based upon single gene sequences. Similarly good
      congruence was found between the discontinuous distribution of phenotypic
      properties and taxa delineated in the phylogenetic trees though diverse non
      monophyletic taxa appeared to be based on the use of plesiomorphic character
      states as diagnostic features.

PMID- 30186310
TI  - NKX2-1 New Mutation Associated With Myoclonus, Dystonia, and Pituitary
      Involvement.
AB  - Background:NKX2-1 related disorders (also known as brain-lung-thyroid syndrome or
      benign hereditary chorea 1) are associated with a wide spectrum of symptoms. The
      core features are various movement disorders, characteristically chorea, less
      frequently myoclonus, dystonia, ataxia; thyroid disease; and lung involvement.
      The full triad is present in 50% of affected individuals. Numerous additional
      symptoms may be associated, although many of these were reported only in single
      cases. Pituitary dysfunction was ambiguously linked to NKX2-1 haploinsufficiency
      previously. Case Presentation: We examined two members of a family with motor
      developmental delay, mixed movement disorder (myoclonus, dystonia and chorea) and
      endocrinological abnormalities (peripheric thyroid disease, and pituitary hormone
      deficiencies). Dystonia predominated at the father, and myoclonus at the
      daughter. The father had hypogonadotropic hypogonadism, while the daughter was
      treated with growth hormone deficiency. Both patients had empty sella on MRI.
      Candidate gene analyses were negative. Exome sequencing detected a pathogenic
      stop variation (NM_003317:c.338G>A, p.Trp113*) in the NKX2-1 gene. Conclusions:
      This case study has two highlights. (1) It draws attention to possible pituitary
      dysfunction in brain-lung-thyroid syndrome, and provide further evidences that
      this might be linked to loss of function of the NKX2-1 gene. (2) It underscores
      the importance of considering NKX2-1 related disorders in the differential
      diagnosis of myoclonus dystonia.

PMID- 30186312
TI  - Comparative Studies of Gene Expression Kinetics: Methodologies and Insights on
      Development and Evolution.
AB  - Across the animal kingdom, embryos of closely related species show high
      morphological similarity despite genetic and environmental distances. Deciphering
      the molecular mechanisms that underlie morphological conservation and those that
      support embryonic adaptation are keys to understand developmental robustness and
      evolution. Comparative studies of developmental gene regulatory networks can
      track the genetic changes that lead to evolutionary novelties. However, these
      studies are limited to a relatively small set of genes and demand extensive
      experimental efforts. An alternative approach enabled by next-generation
      sequencing, is to compare the expression kinetic of large sets of genes between
      different species. The advantages of these comparisons are that they can be done
      relatively easily, for any species and they provide information of all expressed
      genes. The challenge in these experiments is to compare the kinetic profiles of
      thousands of genes between species that develop in different rates. Here we
      review recent comparative studies that tackled the challenges of accurate staging
      and large-scale analyses using different computational approaches. These studies
      reveal how correct temporal scaling exposes the striking conservation of
      developmental gene expression between morphologically similar species. Different
      clustering approaches are used to address various comparative questions and
      identify the conservation and divergence of large gene sets. We discuss the
      unexpected contribution of housekeeping genes to the interspecies correlations
      and how this contribution distorts the hourglass pattern generated by
      developmental genes. Overall, we demonstrate how comparative studies of gene
      expression kinetics can provide novel insights into the developmental constraints
      and plasticity that shape animal body plans.

PMID- 30186313
TI  - Genome-Wide Expression Quantitative Trait Loci Analysis Using Mixed Models.
AB  - Expression quantitative trait loci (eQTLs) are important for understanding the
      genetic basis of cellular activities and complex phenotypes. Genome-wide eQTL
      analyses can be effectively conducted by employing a mixed model. The mixed model
      includes random polygenic effects with variability, which can be estimated by the
      covariance structure of pairwise genomic similarity among individuals based on
      genotype information for nucleotide sequence variants. This increases the
      accuracy of identifying eQTLs by avoiding population stratification. Its
      extensive use will accelerate our understanding of the genetics of gene
      expression and complex phenotypes. An overview of genome-wide eQTL analyses using
      mixed model methodology is provided, including discussions of both theoretical
      and practical issues. The advantages of employing mixed models are also discussed
      in this review.

PMID- 30186315
TI  - Adaptive Image Enhancement Using Entropy-Based Subhistogram Equalization.
AB  - A novel image enhancement approach called entropy-based adaptive subhistogram
      equalization (EASHE) is put forward in this paper. The proposed algorithm divides
      the histogram of input image into four segments based on the entropy value of the
      histogram, and the dynamic range of each subhistogram is adjusted. A novel
      algorithm to adjust the probability density function of the gray level is
      proposed, which can adaptively control the degree of image enhancement.
      Furthermore, the final contrast-enhanced image is obtained by equalizing each
      subhistogram independently. The proposed algorithm is compared with some state-of
      the-art HE-based algorithms. The quantitative results for a public image database
      named CVG-UGR-Database are statistically analyzed. The quantitative and visual
      assessments show that the proposed algorithm outperforms most of the existing
      contrast-enhancement algorithms. The proposed method can make the contrast of
      image more effectively enhanced as well as the mean brightness and details well
      preserved.

PMID- 30186316
TI  - A Novel Teaching-Learning-Based Optimization with Error Correction and Cauchy
      Distribution for Path Planning of Unmanned Air Vehicle.
AB  - Teaching-learning-based optimization (TLBO) algorithm is a novel heuristic method
      which simulates the teaching-learning phenomenon of a classroom. However, in the
      later period of evolution of the TLBO algorithm, the lower exploitation ability
      and the smaller scope of solutions led to the poor results. To address this
      issue, this paper proposes a novel version of TLBO that is augmented with error
      correction strategy and Cauchy distribution (ECTLBO) in which Cauchy distribution
      is utilized to expand the searching space and error correction to avoid detours
      to achieve more accurate solutions. The experimental results verify that the
      ECTLBO algorithm has overall better performance than various versions of TLBO and
      is very competitive with respect to other nine original intelligence optimization
      algorithms. Finally, the ECTLBO algorithm is also applied to path planning of
      unmanned aerial vehicle (UAV), and the promising results show the applicability
      of the ECTLBO algorithm for problem-solving.

PMID- 30186314
TI  - Impact of autologous whole blood administration upon experimental mouse models of
      acute Trypanosoma cruzi infection.
AB  - Background: Autologous whole blood (AWB) administration is described as
      alternative/complementary medical practice widely employed in medical and
      veterinary therapy against infections, chronic pathologies and neoplasias. Our
      aim is to investigate in vivo biological effect of AWB using healthy murine
      models under the course of Trypanosoma cruzi acute infection. Methods: The first
      set of studies consisted of injecting different volumes of AWB and saline (SAL)
      into the posterior region of quadriceps muscle of healthy male Swiss mice under
      distinct therapeutic schemes evaluating: animal behavior, body and organ weight,
      hemogram, plasmatic biochemical markers for tissue damage and inflammatory
      cytokine levels and profile. To assess the impact on the experimental T. cruzi
      infection, different schemes (prior and post infection) and periods of AWB
      administration (from one up to 10 days) were conducted, also employing
      heterologous whole blood (HWB) and evaluating plasma cytokine profile. Results:
      No major adverse events were observed in healthy AWB-treated mice, except gait
      impairment in animals that received three doses of 20 MUL AWB in the same hind
      limb. AWB and SAL triggered an immediate polymorphonuclear response followed by
      mononuclear infiltrate. Although SAL triggered an inflammatory response, the
      kinetics and intensity of the histological profile and humoral mediator levels
      were different from AWB, the latter occurring earlier and more intensely with
      concomitant elevation of plasma IL-6. Inflammatory peak response of SAL, mainly
      composed of mononuclear cells with IL-10, was increased at 24 h. According to the
      mouse model of acute T. cruzi infection, only minor decreases (< 30%) in the
      parasitemia levels were produced by AWB and HWB given before and after infection,
      without protecting against mortality. Rises in IFN-gamma, TNF-alpha and IL-6 were
      detected at 9 dpi in all infected animals as compared to uninfected mice but only
      Bz displayed a statistically significant diminution (p = 0.02) in TNF-alpha
      levels than infected and untreated mice. Conclusions: This study revealed that
      the use of autologous whole blood (AWB) in the acute model employed was unable to
      reduce the parasitic load of infected mice, providing only a minor decrease in
      parasitemia levels (up to 30%) but without protecting against animal mortality.
      Further in vivo studies will be necessary to elucidate the effective impact of
      this procedure.

PMID- 30186311
TI  - Emergence of Members of TRAF and DUB of Ubiquitin Proteasome System in the
      Regulation of Hypertrophic Cardiomyopathy.
AB  - The ubiquitin proteasome system (UPS) plays an imperative role in many critical
      cellular processes, frequently by mediating the selective degradation of
      misfolded and damaged proteins and also by playing a non-degradative role
      especially important as in many signaling pathways. Over the last three decades,
      accumulated evidence indicated that UPS proteins are primal modulators of cell
      cycle progression, DNA replication, and repair, transcription, immune responses,
      and apoptosis. Comparatively, latest studies have demonstrated a substantial
      complexity by the UPS regulation in the heart. In addition, various UPS proteins
      especially ubiquitin ligases and proteasome have been identified to play a
      significant role in the cardiac development and dynamic physiology of cardiac
      pathologies such as ischemia/reperfusion injury, hypertrophy, and heart failure.
      However, our understanding of the contribution of UPS dysfunction in the
      plausible development of cardiac pathophysiology and the complete list of UPS
      proteins regulating these afflictions is still in infancy. The recent emergence
      of the roles of TNF receptor-associated factor (TRAFs) and deubiquitinating
      enzymes (DUBs) superfamily in hypertrophic cardiomyopathy has enhanced our
      knowledge. In this review, we have mainly compiled the TRAF superfamily of E3
      ligases and few DUBs proteins with other well-documented E3 ligases such as MDM2,
      MuRF-1, Atrogin-I, and TRIM 32 that are specific to myocardial hypertrophy. In
      this review, we also aim to highlight their expression profile following
      physiological and pathological stimulation leading to the onset of hypertrophic
      phenotype in the heart that can serve as biomarkers and the opportunity for the
      development of novel therapies.

PMID- 30186317
TI  - Adult Gross Motor Learning and Sleep: Is There a Mutual Benefit?
AB  - Posttraining consolidation, also known as offline learning, refers to
      neuroplastic processes and systemic reorganization by which newly acquired skills
      are converted from an initially transient state into a more permanent state. An
      extensive amount of research on cognitive and fine motor tasks has shown that
      sleep is able to enhance these processes, resulting in more stable declarative
      and procedural memory traces. On the other hand, limited evidence exists
      concerning the relationship between sleep and learning of gross motor skills. We
      are particularly interested in this relationship with the learning of gross motor
      skills in adulthood, such as in the case of sports, performing arts, devised
      experimental tasks, and rehabilitation practice. Thus, the present review focuses
      on sleep and gross motor learning (GML) in adults. The literature on the impact
      of sleep on GML, the consequences of sleep deprivation, and the influence of GML
      on sleep architecture were evaluated for this review. While sleep has proven to
      be beneficial for most gross motor tasks, sleep deprivation in turn has not
      always resulted in performance decay. Furthermore, correlations between motor
      performance and sleep parameters have been found. These results are of potential
      importance for integrating sleep in physiotherapeutic interventions, especially
      for patients with impaired gross motor functions.

PMID- 30186319
TI  - Stress Induced Neuroplasticity and Mental Disorders 2018.

PMID- 30186321
TI  - Histomorphometrical Study on Regional Variation in Distribution of Sweat Glands
      in Buffalo Skin.
AB  - The study was conducted on skin of 24 buffaloes collected from slaughter house.
      The skin tissues were collected from dorsal, lateral, and ventral parts of head,
      neck, thorax, abdomen, and tail regions and fixed in 10% neutral buffered
      formalin. The tissues were processed for paraffin blocks preparation by acetone
      benzene schedule. The paraffin sections of 5-6 MUm were cut with rotary microtome
      and stained with hematoxylin and eosin. The sweat glands in buffaloes were of
      saccular and simple coiled tubular type. Most of the sweat glands were associated
      with hair follicles and consisted of a coiled secretory portion (body) and a
      straight duct. The secretory portion was made up of glandular tubules,
      myoepithelium, and basement membrane. The duct portion had a narrow lumen and was
      lined by simple cuboidal epithelium. The glandular epithelium was simple
      squamous, simple cuboidal, or low columnar type depending upon their stage of
      secretary activity. Two types of sweat glands were observed, i.e., apocrine and
      merocrine. Large number of blood vessels and nerve fibers were observed in the
      vicinity of the sweat glands. In head, neck, and tail regions the maximum number
      of sweat glands/mm2 was observed in dorsal side which did not vary significantly
      (p<0.05) from lateral and ventral side. In abdomen region the number of sweat
      glands/mm2 was maximum on lateral region which varied significantly from ventral
      region (p<0.05). Overall, the maximum number of sweat glands/mm2 was in head
      region followed by abdomen, thorax, neck, and tail but without any significant
      (p<0.05) difference. Maximum sweat gland diameter was found in abdomen region
      followed by thorax, head, neck, and tail region.

PMID- 30186318
TI  - Antidepressant Effects of Probucol on Early-Symptomatic YAC128 Transgenic Mice
      for Huntington's Disease.
AB  - Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder
      caused by a trinucleotide expansion in the HD gene, resulting in an extended
      polyglutamine tract in the protein huntingtin. HD is traditionally viewed as a
      movement disorder, but cognitive and neuropsychiatric symptoms also contribute to
      the clinical presentation. Depression is one of the most common psychiatric
      disturbances in HD, present even before manifestation of motor symptoms.
      Diagnosis and treatment of depression in HD-affected individuals are essential
      aspects of clinical management in this population, especially owing to the high
      risk of suicide. This study investigated whether chronic administration of the
      antioxidant probucol improved motor and affective symptoms as well as hippocampal
      neurogenic function in the YAC128 transgenic mouse model of HD during the early-
      to mild-symptomatic stages of disease progression. The motor performance and
      affective symptoms were monitored using well-validated behavioral tests in YAC128
      mice and age-matched wild-type littermates at 2, 4, and 6 months of age, after 1,
      3, or 5 months of treatment with probucol (30 mg/kg/day via water
      supplementation, starting on postnatal day 30). Endogenous markers were used to
      assess the effect of probucol on cell proliferation (Ki-67 and proliferation cell
      nuclear antigen (PCNA)) and neuronal differentiation (doublecortin (DCX)) in the
      hippocampal dentate gyrus (DG). Chronic treatment with probucol reduced the
      occurrence of depressive-like behaviors in early- and mild-symptomatic YAC128
      mice. Functional improvements were not accompanied by increased progenitor cell
      proliferation and neuronal differentiation. Our findings provide evidence that
      administration of probucol may be of clinical benefit in the management of early-
      to mild-symptomatic HD.

PMID- 30186320
TI  - Functional Connectivity Alterations in Children with Spastic and Dyskinetic
      Cerebral Palsy.
AB  - Cerebral palsy (CP) has long been investigated to be associated with a range of
      motor and cognitive dysfunction. As the two most common CP subtypes, spastic
      cerebral palsy (SCP) and dyskinetic cerebral palsy (DCP) may share common and
      distinct elements in their pathophysiology. However, the common and distinct
      dysfunctional characteristics between SCP and DCP on the brain network level are
      less known. This study aims to detect the alteration of brain functional
      connectivity in children with SCP and DCP based on resting-state functional MRI
      (fMRI). Resting-state networks (RSNs) were established based on the independent
      component analysis (ICA), and the functional network connectivity (FNC) was
      performed on the fMRI data from 16 DCP, 18 bilateral SCP, and 18 healthy
      children. Compared with healthy controls, altered functional connectivity within
      the cerebellum network, sensorimotor network (SMN), left frontoparietal network
      (LFPN), and salience network (SN) were found in DCP and SCP groups. Furthermore,
      the disconnections of the FNC consistently focused on the visual pathway;
      covariance of the default mode network (DMN) with other networks was observed
      both in DCP and SCP groups, while the DCP group had a distinct connectivity
      abnormality in motor pathway and self-referential processing-related connections.
      Correlations between the functional disconnection and the motor-related clinical
      measurement in children with CP were also found. These findings indicate
      functional connectivity impairment and altered integration widely exist in
      children with CP, suggesting that the abnormal functional connectivity is a
      pathophysiological mechanism of motor and cognitive dysfunction of CP.

PMID- 30186322
TI  - Structural Prediction and Mutational Analysis of Rv3906c Gene of Mycobacterium
      tuberculosis H37Rv to Determine Its Essentiality in Survival.
AB  - The emergence of tuberculosis is at the peak; therefore to station it at its
      lower level we hereby try bioinformatics approach against Mycobacterium
      tuberculosis [M. tuberculosis] pathogenesis. Rv3906c is a conserved hypothetical
      gene of M. tuberculosis and contains many GTP binding protein motif DXXG which
      demonstrate that this gene might be processed in a GTP binding or in GTP
      hydrolyzing manner. This gene shows interaction with its adjacent genes as well
      as pcnA which is a polymerase and localized in the extracellular region and found
      to be a soluble protein. Rv3906c has binding pockets for calcium atom at various
      positions which prove that calcium might have some role during the process of
      this gene. GTP binding protein motif DXXG is present in various positions and
      calcium binds at this site with a C-score of 0.25. Mutational analysis on this
      motif shows the large decrease of stability after mutation of aspartate residue
      with glycine. Stress conditions like pH and temperature also change stability of
      the protein. A decrease in stability at this position might play a role in
      inhibition of survival of the pathogen. These computational studies of this gene
      might be a successful step towards drug development against tuberculosis.

PMID- 30186323
TI  - Uterine Artery Doppler in Pregnancy: Women with PCOS Compared to Healthy
      Controls.
AB  - The objective of this study was to investigate possible differences in uterine
      artery pulsatility index (UtAPI) between pregnant women with PCOS and healthy
      controls and to explore possible effects of metformin on UtAPI. Material and
      Methods. The study was conducted in a tertiary center. Forty-eight pregnant women
      diagnosed with PCOS before pregnancy and 124 healthy pregnant women were
      included. Women with PCOS were randomly assigned to metformin 2000 mg daily or a
      placebo. UtAPI was measured five times during 1st and 2nd trimesters of pregnancy
      in women with PCOS and four times in healthy controls. Results. There was no
      difference in UtAPI between PCOS women and healthy controls at any point in time
      (p = 0.34-0.77). In women with PCOS, randomly assigned to metformin 2000 mg or
      placebo, UtAPI was unaffected by metformin two hours after intake of the first
      dose of study medication (p = 0.34). All PCOS women, regardless of randomization,
      had higher UtAPI two hours after intake of study medication and a meal compared
      to before a meal (p = 0.02). Conclusions. In the first and second trimesters of
      pregnancy, there was no difference in UtAPI between women with PCOS and healthy
      controls. Metformin had no immediate effect on the UtAPI. Interestingly, blood
      flow decreased after a meal, suggesting that time since last meal should be taken
      into consideration when interpreting the results of UtAPI measurements in
      pregnancy. This trial is registered with ClinicalTrials.gov (NCT00466622)
      Metformin in Pregnant PCOS women (PregMet) (NCT00159536).

PMID- 30186324
TI  - The Utility of Preoperative Vascular Grading in Patients Undergoing Surgery First
      for Pancreatic Cancer: Does Radiologic Arterial or Venous Involvement Predict
      Pathologic Margin Status?
AB  - Controversy exists on accurately grading vascular involvement on preoperative
      imaging for pancreatic ductal adenocarcinoma. We reviewed the association between
      preoperative imaging and margin status in 137 patients. Radiologists graded
      venous involvement based on the Ishikawa classification system and arterial
      involvement based on preoperative imaging. For patients with both classifications
      recorded, we categorized vascular involvement as "None," "Arterial only," "Venous
      only," or "Both" and examined the association of vascular involvement and
      pathologic margin status. Of 134 patients with Ishikawa classifications, 63%,
      17%, 11%, and 9% were graded as I, II, III, and IV, respectively. Of 96 patients
      with arterial staging, 74%, 16%, and 10% were categorized as stages i, ii, and
      iii, respectively. Of 93 patients with both stagings, 61% had no vascular
      involvement, 7% had arterial only, 14% had venous only, and 17% had both
      involved. Ishikawa classification was strongly associated with a positive SMA and
      SMV margin (p<0.001). However, for arterial staging, there was no association
      with SMA or SMV margin. Overall, Ishikawa grading was more predicative of
      arterial involvement and remained significant on multivariate analysis. The use
      of diagnostic imaging in predicting positive margins is more accurate when using
      a venous grading system.

PMID- 30186326
TI  - Effect of Pressure, Post-Pressing Time, and Polymerization Cycle on the Degree of
      Conversion of Thermoactivated Acrylic Resin.
AB  - Herein, the effect of different post-pressing times and pressure in two cycles of
      polymerization on the degree of conversion (DC) of thermally activated acrylic
      resin (TRRA) is analyzed to optimize the polymerization of this material. After
      post-pressing for 0, 6, or 12 h, polymerization was performed with or without a
      pressure of 60 psi (0.41 MPa) in a short (4 h) or a long (11 h) cycle, totaling
      12 groups. To determine the DC, PMMA specimens were analyzed by Fourier transform
      infrared spectroscopy. The influence of each factor alone on the DC was studied
      by experimental planning. The statistical tests used were three-way ANOVA, t
      test, Tukey's test, and Levene's test, with a margin of error of 5%. Two groups
      prepared with post-pressing times of 12 h had the lowest DC (p < 0.001). Post
      pressing times of 0 and 6 h did not yield statistically different results.
      Pressure increased the DC in only one group (long cycle +12 h, p=0.001). The
      short cycle resulted in a higher DC than the long cycle in 2 groups (with
      pressure +0 h, p=0.002; without pressure +6 h, p=0.015), while the long cycle
      yielded a statistically higher DC in only one group (with pressure +12 h, p <
      0.001). The polymerization showed satisfactory DC in all 12 groups. Small
      differences found among the specimens indicate that the pressure, post-pressing
      time, and polymerization cycles herein were not influential factors for the DC of
      PMMA.

PMID- 30186325
TI  - Fungal-Host Interaction: Curcumin Modulates Proteolytic Enzyme Activity of
      Candida albicans and Inflammatory Host Response In Vitro.
AB  - Current treatments for Candida albicans infection are limited due to the limited
      number of antifungal drugs available and the increase in antifungal resistance.
      Curcumin is used as a spice, food preservative, flavoring, and coloring agent
      that has been shown to have many pharmacological activities. Thus, this study
      evaluated the modulatory effects of curcumin on major virulence factors
      associated with the pathogenicity of C. albicans. The minimum inhibitory
      concentration (MIC) of curcumin against C. albicans (SC5314) was determined.
      Biofilm formation was quantified and the proteinase and phospholipase secretion
      was measured. The cytotoxicity was tested in oral fibroblast cells. A cocultured
      model was used to analyze the gene expression of proinflammatory cytokines (IL
      1beta, IL-1alpha, and IL-6) from host cells, as well SAP-1 and PLB-1 by RT-PCR.
      The MIC was between 6.25 and 12.5 uM, and the activity of proteinase enzyme was
      significantly decreased in biofilms treated with curcumin. However, proteinase
      gene expression was not downregulated after curcumin treatment. Furthermore, gene
      expressions of host inflammatory response, IL-1beta and IL-1alpha, were
      significantly downregulated after exposure to curcumin. In conclusion, curcumin
      exhibited antifungal activity against C. albicans and modulated the proteolytic
      enzyme activities without downregulating the gene expression. In host
      inflammatory response, curcumin downregulated IL-1beta and IL-1alpha gene
      expression.

PMID- 30186327
TI  - Corrigendum to "GC Method Validation for the Analysis of Menthol in Suppository
      Pharmaceutical Dosage Form".
AB  - [This corrects the article DOI: 10.1155/2017/1728414.].

PMID- 30186328
TI  - A Rare Cause of Acute Kidney Injury: Primary Renal Lymphoma in a Patient with
      Human Immunodeficiency Virus.
AB  - We reported a case of primary renal lymphoma (PRL) presented with non-oliguric
      acute kidney injury and bilateral kidney infiltrates in an individual with human
      immunodeficiency virus (HIV) disease. Acute kidney injury secondary to lymphoma
      infiltrates is very rare (less than 1% of hematological malignancy). A 37-year
      old gentleman with underlying human immunodeficiency virus (HIV) disease was on
      combined antiretroviral therapy since diagnosis. He presented to our center with
      uremic symptoms and gross hematuria. Clinically, bilateral kidneys massively
      enlarged and were ballotable. Blood investigations showed hemoglobin of 3.7 g/L,
      urea of 65.6 mmol/L, and serum creatinine of 1630 umol/L with hyperkalemia and
      metabolic acidosis. An urgent hemodialysis was initiated, and he was dependent on
      regular hemodialysis subsequently. Computed tomography renal scan showed diffuse
      nonenhancing hypodense lesion in both renal parenchyma. Diagnosis of diffuse
      large B cell lymphoma with germinal center type, CD20 positive, and proliferative
      index 95% was confirmed via renal biopsy, and there was no bone marrow
      infiltrates. Unfortunately, the patient succumbs prior to initiation of
      chemotherapy.

PMID- 30186329
TI  - Safety of Autologous Cord Blood Cells for Preterms: A Descriptive Study.
AB  - Background: Preterm birth complications are one of the leading causes of death
      among children under 5 years of age. Despite advances in medical care, many
      survivors face a lifetime of disability, including mental and physical
      retardation, and chronic lung disease. More recently, both allogenic and
      autogenic cord blood cells have been applied in the treatment of neonatal
      conditions such as hypoxic-ischemic encephalopathy (HIE) and bronchopulmonary
      dysplasia (BPD). Objective: To assess the safety of autologous, volume- and red
      blood cell- (RBC-) reduced, noncryopreserved umbilical cord blood (UCB) cell
      infusion to preterm infants. Method: This study was a phase I, open-label, single
      arm, single-center trial to evaluate the safety of autologous, volume- and RBC
      reduced, noncryopreserved UCB cell (5 * 107cells/kg) infusion for preterm infants
      <37 weeks gestational age. UCB cell characteristics, pre- and postinfusion vital
      signs, and laboratory investigations were recorded. Clinical data including
      mortality rates and preterm complications were recorded. Results: After
      processing, (22.67 +/- 4.05) ml UCB cells in volume, (2.67 +/- 2.00) * 108 cells
      in number, with (22.67 +/- 4.05) * 106 CD34+, (3.72 +/- 3.25) * 105 colony
      forming cells (CFU-GM), and (99.7 +/- 0.17%) vitality were infused to 15 preterm
      infants within 8 hours after birth. No adverse effects were noticed during
      treatment. All fifteen patients who received UCB infusion survived. The duration
      of hospitalization ranged from 4 to 65 (30 +/- 23.6) days. Regarding preterm
      complications, no BPD, necrotizing enterocolitis (NEC), retinopathy of
      prematurity (ROP) was observed. There were 1/15 (7%) infant with intraventricular
      hemorrhage (IVH), 5/15 (33.3%) infants with ventilation-associated pneumonia, and
      10/15 (66.67%) with anemia, respectively. Conclusions: Collection, preparation,
      and infusion of fresh autologous UCB cells to preterm infants is feasible and
      safe. Adequately powered randomized controlled studies are needed.

PMID- 30186331
TI  - Household Food Insecurity and Psychosocial Dysfunction in Ecuadorian Elementary
      Schoolchildren.
AB  - Household food insecurity (HFI) is a major global public health and pediatric
      concern due to its reported association with adverse child nutrition, growth, and
      health outcomes. Psychosocial dysfunction is a major cause of childhood
      disability. US and Canadian studies have linked HFI to poorer overall
      psychosocial dysfunction and specific dysfunction types in school-aged children,
      i.e., internalizing, externalizing, and attention behaviors. However, it is
      uncertain whether prior findings are generalizable to low- and middle-income
      country (LMIC) settings. We conducted a cross-sectional study to explore the
      association of HFI with psychosocial dysfunction in 6-12-year-old public
      elementary schoolchildren (n=279) residing in low-income neighborhoods in Quito,
      Ecuador. Maternal caregivers were interviewed to obtain data on child
      psychosocial dysfunction (Pediatric Symptom Checklist, PSC), food security
      (Household Food Security Survey Module), and maternal mental health (SF-36 Mental
      Composite Summary). Capillary blood samples were obtained from child participants
      to measure hemoglobin levels. The data were analyzed using general linear models
      with adjustment for covariates. The results revealed that HFI was associated with
      significantly higher overall average PSC scores (p=0.002) and with internalizing
      (p=0.001) and externalizing (p=0.03) but not attention subscale scores. However,
      anemia was independently associated with PSC attention subscale scores (p=0.015).
      This is the first study to report on the relationship between HFI and
      psychosocial dysfunction in school-aged children in a LMIC setting. It highlights
      the importance of improving policies and programs protecting vulnerable
      households from HFI. In addition to improving health and nutrition, such
      improvements could potentially reduce the burden of child psychosocial
      dysfunction.

PMID- 30186330
TI  - Human Bone Marrow Mesenchymal Stem Cells Promote Gastric Cancer Growth via
      Regulating c-Myc.
AB  - The clinical application of human bone marrow mesenchymal stem cells (hBM-MSCs)
      has generated a great deal of interest because of their potential use in
      regenerative medicine and tissue engineering. However, safety concerns over hBM
      MSCs limit their clinical application. In this study, we observed that hBM-MSC
      conditioned medium (hBM-MSC-CM) promotes gastric cancer development via
      upregulation of c-Myc. Our results showed that c-Myc was upregulated in MGC-803
      and BGC-823 cells after hBM-MSC-CM treatment. Moreover, we found that the c-Myc
      inhibitor JQ1 and c-Myc siRNA decreased the expression of c-Myc in hBM-MSC-CM
      treated tumor cells in vitro. Additionally, hBM-MSC-CM enhanced the migration and
      glucose uptake of gastric cancer cells. In vivo studies showed that JQ1 inhibited
      hBM-MSC-CM-induced gastric cancer growth. These results indicated that hBM-MSC-CM
      induced gastric cancer growth via upregulation of c-Myc, which may be a potential
      risk factor and/or a therapeutic target for clinical applications.

PMID- 30186332
TI  - Food Safety Analysis of Milk and Beef in Southwestern Uganda.
AB  - Background: Inorganic pollutants in milk and beef are of major public health
      concern; however, information in Africa is still limited due to low food safety
      monitoring practices. In this study, we established levels of lead (Pb), zinc
      (Zn), cadmium (Cd), copper (Cu), and iron (Fe) in milk and beef and obtained the
      estimated daily intake (EDI) and incremental lifetime cancer risk (ILCR) as
      measures of risk to the Ugandan population. Materials and Methods: This was a
      cross-sectional study in which a total of 40 samples of milk and beef were
      collected from Bushenyi district in southwestern Uganda. Samples were analyzed by
      atomic absorbance spectrophotometer, and the EDI and ILCR were computed using the
      US EPA reference values. Results and Discussion: Heavy metal concentrations were
      highest in the order of Zn > Fe > Pb > Cu in milk samples, while in beef samples,
      concentrations were highest in the order of Zn > Pb > Fe > Cu and no Cd was
      detected. Furthermore, beef had significantly higher (P < 0.05) Pb and Fe
      concentrations than milk. The EDI was highest in children, and this was followed
      by very high ILCR levels, showing that milk and beef are not safe for children in
      Uganda. Bearing in mind that a high HI was shown, beef and milk from these
      regions are not recommended for consumption especially by children although more
      studies remain to be conducted. Conclusion: Heavy metals in milk and beef of
      Uganda may predispose the indigenous community to cancer and other health-related
      illnesses, showing a need for improved food safety screening to promote food
      safety.

PMID- 30186333
TI  - Preliminary Study: Environmental Assessment of Perchloroethylene in Dry-Cleaning
      Facilities in the UAE.
AB  - Background: Perchloroethylene (PERC) is a widely spread cleaning solvent, used in
      nearly all dry-cleaning facilities. It has been declared as "probable human
      carcinogen" by the International Agency for Research on Cancer (IARC) due to its
      hazardous and toxic effects on human health. The study aimed at assessing the
      exposure of PERC among dry-cleaning workers at four different dry-cleaning
      facilities in the UAE. Methods: The four dry-cleaning facilities, using PERC in
      one of the cities of the UAE, were selected. Draeger perchloroethylene 10/b
      detector tubes along with a Draeger accuro pump were used to estimate the levels
      of PERC exposure in three main selected positions in each of the facilities.
      Results: The results showed that the second selected position had the highest
      amounts of PERC exposure above the international and local standards in 3 out of
      4 selected facilities. The workers at position 2, who were not using any of the
      provided personal protective equipment, were at the highest risk of developing
      PERC-related health problems. Conclusion: It is important to install local
      exhaust ventilation systems and monitoring devices of PERC concentrations in
      these facilities, along with raising the awareness of workers about the health
      effects of PERC and the importance of using personal protective equipment (PPE)
      while performing their job.

PMID- 30186334
TI  - Factors Affecting Intention to Disclose HIV Status among Adult Population in
      Sarawak, Malaysia.
AB  - Background: Disclosure of HIV-positive status is an essential prerequisite for
      the prevention and care of person living with HIV/AIDS as well as to tackle
      hidden epidemic in the society. Objective: To determine the intention to disclose
      the HIV/AIDS status among adult population in Sarawak, Malaysia, and factors
      affecting thereof. Methods: This cross-sectional community-based study was
      conducted among adult population aged 18 years and above in Sarawak, Malaysia. A
      gender-stratified multistage cluster sampling technique was adopted to select the
      participants. A total of 900 respondents were successfully interviewed by face-to
      face interview using interview schedule. Stepwise binary logistic regression
      models were fitted in SPSS version 22.0 to identify the factors associated with
      the disclosure of HIV/AIDS status. A p value less than 0.05 was considered as
      statistically significant. Results: The mean (SD) age of male and female
      respondents was 41.57 (13.45) and 38.99 (13.09) years, respectively. A
      statistically significant difference of intention to disclosure of HIV status was
      found between males and females (p < 0.05). A stepwise binary logistic regression
      analysis revealed that age, occupation, knowledge on HIV transmission, and
      content of discussion about HIV/AIDS appeared to be potential predictors for male
      respondents to disclose HIV status, while ethnicity and content of discussion on
      HIV/AIDS were found to be important predictors among the female respondents (p <
      0.05). Conclusion and Recommendation: Though the study did not depict the
      national prevalence of disclosure of HIV/AIDS status, the findings of the study
      would provide an important basic information for programme intervention, policy,
      and future research agenda.

PMID- 30186335
TI  - Common allergies in urban adolescents and their relationships with asthma control
      and healthcare utilization.
AB  - Background: Urban adolescents suffer a disproportionate burden of asthma
      morbidity, often in association with allergies. Literature is limited on
      comparing various types of allergies regarding prevalence and associations with
      asthma morbidity in urban dwelling adolescents. The purpose of this study was to
      examine the prevalence of common allergies reported by urban adolescents and to
      assess their relationships to healthcare utilization and asthma control. Methods:
      Study participants included 313 urban adolescents (12-20 years of age) with
      persistent asthma who were recruited from three states in the United States. Self
      report data were collected on nine indoor and outdoor allergies, healthcare
      utilization, and asthma exacerbation. Logistic regressions and zero-inflated
      Poisson regressions were conducted to examine the relationships between allergies
      and asthma morbidity. Results: The mean age of participants was 14.58 (+/- 1.97)
      and 52% were female, and 79% were black. Seventy-three percent (n = 229) reported
      one or more allergies. Dust mite and grass allergies were most common, each
      reported by 50%. The prevalence of pest allergies (cockroach and mouse) was 27.5%
      and 19%, respectively. Those with pest allergies were more likely to report ED
      visits (cockroach- Odds Ratio (OR) = 2.16, 95% CI 1.18-3.94, p = .01; mouse- OR =
      2.13, 95% CI 1.09-4.07, p = .02), specialist visits (cockroach-OR = 2.69, 95% CI
      1.60-4.54, p < .001; mouse- OR = 2.06, 95% CI 1.15-3.68, p = .01) and asthma
      exacerbation (cockroach-OR = 2.17, 95% CI 1.26-3.74, p < .001; mouse- OR = 2.30,
      95% CI 1.26-4.18, p = .01). Cockroach allergies were associated with 2.2 times as
      many nights in the hospital (95% CI 1.053-3.398, p = 0.036) and 2.2 times as many
      specialist visits (95% CI 1.489-3.110, p < 0.001), and mouse allergy was
      associated with 1.6 times as many ED visits (95% CI 1.092-2.257, p = 0.015)
      compared to those without pest allergies. Conclusions: Concomitant occurrence of
      allergies is ubiquitous among urban adolescents with asthma. Only pest allergies,
      of those examined, appear to have implications for poorly controlled asthma,
      exacerbation and acute healthcare utilization. To reduce asthma burden in urban
      adolescents, identification and management of high-risk adolescents with pest
      allergen sensitization and exposure are warranted.

PMID- 30186336
TI  - Challenges of Family Caregivers of Patients with Mental Disorders in Iran: A
      Narrative Review.
AB  - Background: Family caregivers of patients with mental disorders play the most
      important role in the care of psychiatric patients (PPs) and preventing their
      readmission. These caregivers face different challenges in different cultures. We
      conducted this study to determine the challenges of caregivers of patients with
      mental disorders in Iran. Materials and Methods: This study is a narrative review
      with a matrix approach conducted by searching electronic databases, SID,
      IRANMEDEX, MAGIRAN, PUBMED, SCOPUS, Web of Sciences, from February 2000 to 2017.
      Searched keywords include challenges, family caregivers of psychiatric patient,
      family caregivers and psychiatric patient, mental illness, families of
      psychiatric patient, and Iran. One thousand two hundred articles were found in
      English and Farsi, and considering inclusion and exclusion criteria, 39 articles
      were examined. Results: The results of the studies show that not meeting the
      needs of caregivers, burnout and high burden of care, high social stigma, low
      social support for caregivers, and low quality of life of caregivers were among
      the most important challenges faced by caregivers. Conclusions: Despite the
      efforts of authorities in Iran, family caregivers of patients with mental
      disorders still face challenges. Therefore, the need for all-inclusive support
      for family caregivers of patients with mental health problems is necessary.

PMID- 30186337
TI  - The Viewpoints of Managers and Healthcare Providers on Individual Barriers to
      Perform Preconception Care for Diabetic Women.
AB  - Background: Individual barriers can affect the provision of preconception care
      (PCC). The aim of the present study was to determine the rank of importance of
      individual barriers (care recipients) in the provision of PCC among diabetic
      women from the viewpoints of care providers. Materials and Methods: The present
      cross-sectional study was conducted on 212 health managers, physicians, and
      midwives from December 2015 to March 2016. The data collection tool was a two
      part researcher-made questionnaire consisting of a demographic characteristics
      and viewpoints scored on a five-point Likert scale (range: 0-4). Data were
      analyzed in Statistical Package for the Social Sciences software. Results: The
      mean (SD) individual barriers score of physicians, midwives, and health managers
      were 57.33 (15.63), 61.53 (17.81), and 54.57 (16.95), respectively (range: 0
      100). A significant difference was observed between the three groups in terms of
      the mean score of importance of individual barriers (F = 2.54, df = 2, p =
      0.040). Insufficient understanding of the importance of PCC by diabetic women and
      their families obtained the highest mean rank of importance in all groups.
      Conclusions: Although individual barriers had more importance in access to PCC by
      diabetic women in the view of midwives compared to the other groups, the
      viewpoints of the three groups were similar in most cases regarding the rank of
      importance of items. In order to improve the quality of PCC, the necessary
      measures must be taken by authorities and care providers to eliminate important
      barriers.

PMID- 30186338
TI  - Characteristics of Shared Governance in Iranian Nursing Schools: Several Souls in
      One Body.
AB  - Background: Shared governance is a decentralized structural model that gives
      individuals the right to make decisions and a position analogous to managers. The
      shared governance is different based on context in every organization. This study
      identified the characteristics of shared governance in Iranian nursing schools.
      Materials and Methods: In this qualitative research, 11 participants were
      selected using purposive sampling method. Deep semi-structured interviews were
      conducted, and the data were analyzed using conventional content analysis.
      Lincoln and Guba's criteria were used to verify the accuracy and trustworthiness
      of the data. Results: Through data analysis, the theme of "several souls in one
      body" was achieved in addition to the seven categories of "climates based on
      common interests," "conscious participatory decision-making," "mutual
      accountability," "multiplicity of ideas," "decentralized structure,"
      "interrelationship," and "sublime organization." Conclusions: According to the
      findings, the characteristics of shared governance in the social culture of Iran
      are like several souls in one body, emphasizing all aspects of participation and
      morality in the organization. Managers and administrators in higher education and
      nursing faculties need to pay attention to all aspects of shared governance,
      including spirituality in managing the covered institutions.

PMID- 30186340
TI  - The Effect of Using Communication Boards on Ease of Communication and Anxiety in
      Mechanically Ventilated Conscious Patients Admitted to Intensive Care Units.
AB  - Background: Using mechanical ventilation devices has unique advantages for the
      patient; however, it can also cause various problems. This study aimed to
      determine the effect of using communication boards on the ease of communication
      and anxiety in mechanically ventilated conscious patients admitted to intensive
      care units (ICUs). Materials and Methods: In this quasi-experimental study, 30
      conscious patients undergoing mechanical ventilation were enrolled using
      consecutive sampling method and assigned to experimental (n = 15) and control (n
      = 15) groups. The control group included patients receiving primary communication
      methods, whereas the experimental group included patients who used the
      communication board for communication. The Hospital Anxiety and Depression Scale
      (HADS) and Ease of Communication Scale (ECS) were completed for both groups. Data
      were analyzed using descriptive-inferential statistics. Results: Communication
      scores of the patients indicated that there was no significant difference between
      the control and experimental groups before the intervention (z = -1.77; p =
      0.070). However, after the intervention, there was a significant difference in
      communication scores between the two groups (z = -4.69; p = 0.001). The anxiety
      scale scores showed a significant difference between the control and experimental
      groups after the intervention, and patients' anxiety had significantly decreased
      in the experimental group (z = -2.98; p = 0.003). Conclusions: The results showed
      that the use of the communication board is possible in mechanically ventilated
      conscious patients and may contribute to ease of communication and decrease
      patients' anxiety during mechanical ventilation.

PMID- 30186339
TI  - Comparing the Effects of Face-to-face and Video-based Education on Inhaler Use: A
      Randomized, Two-group Pretest/posttest Study.
AB  - Background: The quality of inhaler use can significantly affect the effectiveness
      of inhalation medications. This study was done to compare the effects of face-to
      face and video-based education methods on inhaler use. Materials and Methods: A
      quasi-experimental, pretest/posttest clinical trial study was conducted on 120
      patients with respiratory diseases who were under treatment with metered-dose
      inhalers. Patients were randomly allocated into two groups to receive either face
      to-face (n = 60) or video-based education (n = 60) about correct inhaler use.
      Inhaler use was assessed using a 15-item checklist before, 2 weeks, and 1 month
      after the education. Chi-square and independent sample t-test as well as repeated
      measures analysis of variance were used for data analysis. Results: At baseline,
      the groups did not differ significantly in inhaler use as shown by the mean score
      (t = 0.81, p = 0.33). Repeated-measures analysis showed that the mean score of
      inhaler use significantly increased in both groups 2 weeks and 1 month after the
      intervention (F = 585.07, p < 0.001). The t-test showed that at 2 weeks and 1
      month after intervention the amount of increase in the face-to-face group was
      significantly greater than the video-based group (t = 3.31 and 5.93, p < 0.001).
      Conclusions: Both face-to-face and video-based education methods significantly
      improve inhaler use, even though the effects of the face-to-face method are
      significantly greater. Nurses can use either of these two methods or both for
      education of patients about inhaler use.

PMID- 30186341
TI  - The Meaning of Managerial Competency of ICU Head Nurses in Iran: A
      Phenomenological Study.
AB  - Background: The health system in Iran faces specific challenges as the managerial
      role of head nurses have changed. The importance of this role cannot be
      underestimated for the healthcare organizations' success. The present study was
      conducted to explore the meaning of managerial competence of head nurses in
      intensive care units (ICU) in Iran. Materials and Methods: This study used a
      qualitative approach. We extracted the lived experience of ten Iranian ICU head
      nurses. Data were collected through unstructured in-depth interviews from 2014 to
      2015. Interviews were recorded and transcribed verbatim and were interpreted
      using Van Manen's six-step approach. Results: The expansion and clustering of 442
      initial themes led to the emergence of 35 secondary themes, nine subthemes, and
      three main themes. Managerial competence - theme included "self-excellence,"
      "ward excellence," and "intensive care excellence." Conclusions: The "managerial
      competence of ICU head nurses" is a dynamic concept that reflects the
      psychological and functional capability of head nurses in contributing towards
      excellence in their own critical care practice as well as that of the ward. A
      competent head nurse has outstanding personal and nursing attributes and holistic
      knowledge, and is also committed to the ongoing professional improvement of
      him/herself. Using their ability to facilitate interpersonal and
      interprofessional communication effectively, a head nurse seeks the
      psychological, physical, and human optimization of the ward in which he/she
      works. Therefore, the goal of providing insightful critical care through smart
      organization and planning of nurses and other personnel can be achieved.

PMID- 30186342
TI  - Investigating the Effect of Reflexology on the Breast Milk Volume of Preterm
      Infants' Mothers.
AB  - Background: Reflexology is an interventional method which may lead to improved
      breast milk. Because the mechanism of milk production is complex, detailed
      research is required on the relationship between lactation and reflexology.
      Therefore, the aim of the present study was to determine the effect of
      reflexology on the volume of milk among mothers with premature infants. Materials
      and Methods: This clinical trial was conducted among 50 mothers with premature
      infants in two groups of 25 patients admitted to the neonatal intensive care unit
      of Alzahra and Shahid Beheshti hospitals of Isfahan, Iran from August 2015 to
      November 2015. The patients were selected through convenience sampling method and
      divided into control and reflexology groups through random allocation. In the
      reflexology group, massage of the sole of the foot and foot was done in six
      sessions. The control group received regular breastfeeding training. Data were
      analyzed using descriptive and inferential statistics. Results: Repeated-measures
      analysis of variance test indicated that the mean volume of breast milk in
      reflexology group (F = 44.002, p < 0.001) and control group (F = 43.09, p <
      0.001) differed significantly at different times. Independent t-test showed that
      the mean increase in milk volume from day 1 to day 5 after the intervention
      compared to before the intervention was significantly higher in the reflexology
      group compared to the control group 1days after the intervention (t=5.25, p
      <0.001), 2 days after the intervention (t= 4.81, p <0.001), 3 days after the
      intervention (t=3.55, p =0.001), 4 days after the intervention (t= 2.98, p
      =0.004), 5 days after the intervention (t= 2.50, p =0.020). Conclusions: The
      results indicate that reflexology is effective on the volume of milk of mothers,
      and this low-cost and easy procedure can be used along with regular lactation
      training.

PMID- 30186343
TI  - The Perception and Experience of Infertile Women Who Received Acupressure in
      Relation to Anxiety: A Qualitative Study.
AB  - Background: Women, who are in a critical situation like infertility, are more
      prone to depression, anxiety, and low self-esteem than other people. The aim of
      this study was to explore the deep experience of anxiety in infertile women who
      received acupressure during in vitro fertilization/intracytoplasmic sperm
      injection (IVF/ICSI). Materials and Methods: This qualitative, conventional
      content analysis study was performed on 14 infertile female participants in the
      Milad IVF Center in Mashhad, Iran, from September 2015 to August 2016. The study
      subjects included Iranian women, aged 20-45 (mean [standard deviation, SD] 29.07
      [4.06]) years with primary infertility. Acupressure was performed on the Heart 7
      and Pericardium 6 acupoints in 12 sessions. Data were gathered through semi
      structured interviews, and transcribed, coded, and organized in different
      categories based on three primary phases of preparation, organization, and
      reporting. Results: The results showed the two major categories of "body
      perceptions of anxiety diminution" and "mind experiences." The body perceptions
      category consisted of three subcategories, namely, reduction of nervous,
      cardiovascular, and gastrointestinal signs and symptoms. The subcategories of the
      mind experiences category consisted of emotional and cognitive consequences.
      Conclusions: The qualitative findings showed a number of positive outcomes in the
      physical and mental signs and symptoms of anxiety in infertile women undergoing
      IVF/ICSI, so acupressure can be used for reducing the unpleasant feelings and
      body perceptions of these women.

PMID- 30186344
TI  - Needlestick Injuries among Healthcare Workers: Why They Do Not Report their
      Incidence?
AB  - Background: Needlestick injuries (NSIs) among healthcare workers (HCWs) pose an
      important health challenge and several pieces of evidence show that in many cases
      HCWs do not report the injury. Materials and Methods: This multicenter
      descriptive cross-sectional study was performed in eight teaching hospitals of
      Rasht, Iran. Using consecutive sampling methods, 1010 nurses were enrolled from
      October 2014 to January 2015. A three-part self-administered questionnaire was
      used. It included questions on demographic features, NSI-related questions, and
      questions on the knowledge of hepatitis B and C viruses (HCV, HBV). Results:
      Among the 1010 participants, 580 (57.42%) showed a positive history of NSI; the
      total number of occurrences of NSI was 914. The major item causing NSI was the
      syringe with needle (315; 34.47%). In this way, NSIs occurred most frequently
      during recapping and injection [339 (37.10%) and 147 (16.10%), respectively].
      Only 92 (10.07%) of all NSI positive participations had referred to the infection
      control units of their hospitals. The others mostly answered the question of "Why
      did you not report the incident?" with being too busy at work at the time of
      injury (140; 27.58%). The results showed that among participants with <5 years
      elapsed since their vaccination, the risk of NSI reduced to 60% [p < 0.02, odds
      ratio (OR) = 0.40, 95% confidence interval (CI) = 0.20-0.80]. Conclusions: It
      seems that NSI is still a major problem among nurses. Correspondingly, HCWs do
      not take the reporting system seriously and training them requires an ongoing
      activity in all hospitals.

PMID- 30186345
TI  - The Effect of Relaxation Technique on Fatigue Levels after Stem Cell Transplant.
AB  - Background: Many patients undergoing hematopoietic stem cell transplant (HSCT)
      experience fatigue due to their disease process and its long period of treatment.
      Using nonpharmacological methods to help reduce their fatigue is a reasonable
      endeavor. The present study was conducted to investigate the effect of Benson's
      relaxation technique on fatigue levels in patients after HSCT. Materials and
      Methods: Thirty-seven patients were randomly selected to the intervention (n =
      19) and control group (n = 18). In the intervention group, the participants
      performed Benson's relaxation exercises for 20 min twice per day over a period of
      15 days. The data collection tools used included a demographic and medical
      information form and the Brief Fatigue Inventory, completed by both groups on
      three different occasions (upon admission and days 8 and 14 after the HSCT). The
      data obtained were analyzed in Statistical Package for the Social Sciences
      version-20 using statistical tests. Results: The results of the independent t
      test showed no significant preintervention differences in fatigue levels between
      the two groups. On days 8 (t = 11.21, p < 0.001) and 14 after the transplant (t =
      15.62, p < 0.001), a significant difference was observed in the mean level of
      fatigue between the two groups. Conclusions: These findings indicate that
      Benson's relaxation technique would improve fatigue in HSCT patients.

PMID- 30186346
TI  - The Effects of Inhalation Aromatherapy with Rose and Lavender at Week 38 and
      Postpartum Period on Postpartum Depression in High-risk Women Referred to
      Selected Health Centers of Yazd, Iran in 2015.
AB  - Background: Postpartum depression (PPD) is one of the most common problems in
      women of childbearing age. This study was conducted to evaluate the efficacy of
      aromatherapy on PPD. Materials and Methods: In this study, 105 pregnant women at
      35-37 weeks of pregnancy were enrolled using convenient sampling and randomly
      assigned to three groups. The intervention group dropped 7 drops of lavender oil
      and 1 cc rose water at the concentration of 100%, and the placebo group dropped 7
      drops of odorless sesame seed oil, with 1 cc of musk willow sweat at the
      concentration of 100% by dropper on a special cloth. They put the cloths on their
      mouths and took 10 deep breaths before sleeping and then placed them next to
      their pillows. The control group only received the routine care. The intervention
      lasted from 38th week of pregnancy until 6 weeks after delivery. Then depression
      level was determined before the intervention, 35-37 weeks of pregnancy, 2 and 6
      weeks after delivery using Edinburgh questionnaire. Results: The mean of
      depression score in the intervention group decreased significantly compared to
      the placebo and control groups, 2 weeks (F = 9.412, p < 0.001) and 6 weeks after
      delivery (F = 7.813, p < 0.01). Conclusions: This study provides valid evidence
      for the effect of aromatherapy on PPD. Therefore, the use of aromatherapy can be
      recommended in high.

PMID- 30186348
TI  - High-efficiency Strategies to Improve Health Information of the General
      Population.

PMID- 30186347
TI  - The Vulnerability of the Iranian Elderly in Disasters: Qualitative Content
      Analysis.
AB  - Background: Elderly people are among the most vulnerable groups in natural
      disaster events. Although old age is responsible for them becoming unequally
      vulnerable, understanding the different aspects of vulnerability can help health
      care providers, especially nurses, to manage disaster risk for this increasing
      number of people. This study intended to explore disaster-related vulnerability
      and its contributing factors based on older adults' perceptions and experiences.
      Materials and Methods: This qualitative content analysis study was performed in
      Iran in 2016. The study was conducted by semi-structured interviews of 24
      participants, and purposeful sampling with maximum variation continued until data
      saturation. Results: By analyzing primary codes two main themes were extracted
      through content analysis, namely personal factors and social factors, from
      experiences of two experts in the field of health in emergencies and disaster
      management among 22 Iranian elderly participants. Conclusions: This study
      indicated that age is not the only criteria that makes an elderly person
      vulnerable, but their lifetime achievements and experiences can determine their
      level of vulnerability. The results of this study will help health service
      providers as well as disaster nurses to identify and moderate the factors
      affecting the vulnerability of the elderly, and by using their rich experience,
      enhance senior citizens' resilience to disasters.

PMID- 30186349
TI  - Mothers and Low Birth Weight Infants: A Holistic Perspective.

PMID- 30186350
TI  - Inhibition of Aortic Intimal Hyperplasia and Vascular Smooth Muscle Proliferation
      and Extracellular Matrix Protein Expressions by Astragalus-Angelica Combination.
AB  - VSMC proliferation and ECM deposition always resulted in intimal hyperplasia.
      Astragalus-Angelica combination has a protective effect on the cardiovascular
      system. The inhibition effect of different Astragalus-Angelica combination on the
      hyperplastic intima after vascular balloon injury in rats was investigated in
      this study. Astragalus-Angelica combination can inhibit the intima hyperplasia
      after balloon injury, in which a 1:1 ratio shows excellent results. Astragalus
      Angelica combination can enhance the expression of smooth muscle alpha-actin (SMa
      actin) and inhibit the expression of proliferating cell nuclear antigen (PCNA),
      cyclin D1, cyclin E, collagen I (Col-I), fibronectin (FN), and matrix
      metallopeptidase-9 (MMP-9) in hyperplastic intima, suggesting that Astragalus
      Angelica combination can inhibit the intimal hyperplasia of blood vessels in
      rats. The mechanism is related to the inhibition of PI3K/Akt signaling pathway
      activation and thereby inhibits the phenotypic transformation and cell
      proliferation of VSMCs and thus inhibits the extracellular matrix (ECM)
      deposition of vascular wall during intimal hyperplasia.

PMID- 30186351
TI  - Cytotoxic Effect of Thymoquinone-Loaded Nanostructured Lipid Carrier (TQ-NLC) on
      Liver Cancer Cell Integrated with Hepatitis B Genome, Hep3B.
AB  - Thymoquinone (TQ), a bioactive compound found in Nigella sativa, cannot be orally
      consumed due to its lipophilicity. In order to overcome this low bioavailability,
      TQ is loaded into a colloidal drug carrier known as a nanostructured lipid
      carrier (NLC). This study aims to determine the antiproliferative effects of TQ
      and TQ-NLC on liver cancer cells integrated with the hepatitis B genome, Hep3B.
      The Hep3B was treated with TQ or TQ-NLC for 24, 48, and 72 hours via MTT assay.
      The results confirm that TQ or TQ-NLC inhibited the growth of Hep3B at IC50 <16.7
      MUM for 72 hours. TQ was also found to induce cell cycle arrest at the G1
      checkpoint while TQ-NLC induced non-phase-specific cell cycle arrest. Further
      analysis using Annexin V staining confirmed the apoptotic induction of TQ or TQ
      NLC via activation of caspases-3/7. In ROS management, TQ acted as a prooxidant
      (increased the level of ROS), while TQ-NLC acted as an antioxidant (reduced the
      level of ROS). Molecular analysis demonstrated that the GSH system and the
      Nrf2/Keap1 signaling pathway in Hep3B influenced the differential responses of
      the cells towards TQ or TQ-NLC. Hence, this study demonstrated that TQ and TQ-NLC
      have in vitro anticancer effects on the Hep3B.

PMID- 30186352
TI  - Effects of Tai Chi on Self-Efficacy: A Systematic Review.
AB  - The purpose of this systematic review is to summarize and update the readers
      regarding clinical studies that have investigated the effects of Tai Chi on self
      efficacy and to describe their limitations and biases. Nine electronic databases
      were searched from the establishment of the database until August 10, 2017. All
      randomized controlled trials (RCTs), nonrandomized controlled studies (NRSs),
      quasi-experimental studies, or studies with pre-post design were included if they
      clearly defined a Tai Chi intervention and evaluated self-efficacy outcomes. We
      categorized these 27 studies into the "disease category" and the "population
      category," based on the types of participants. This systematic review summarizes
      the effects of Tai Chi on self-efficacy in various populations and found that Tai
      Chi appeared to have positive effects on self-efficacy in some populations.
      Fifteen research studies showed that Tai Chi had significant positive effects on
      self-efficacy, while 11 studies did not; only one study found a negative outcome
      at the follow-up. In addition, it is unclear which type, frequency, and duration
      of Tai Chi intervention most effectively enhanced self-efficacy. Tai Chi appears
      to be associated with improvements in self-efficacy. Definitive conclusions were
      limited due to the variation in study designs, type of Tai Chi intervention, and
      frequency, and further high-quality studies are required.

PMID- 30186353
TI  - Paeonol Ameliorates Ovalbumin-Induced Asthma through the Inhibition of TLR4/NF
      kappaB and MAPK Signaling.
AB  - Asthma is a chronic inflammatory disease of the airways, with complex signaling
      pathways involved in its pathogenesis. It was reported that paeonol attenuated
      airway inflammation of ovalbumin (OVA)-induced mice. Therefore, it is of
      importance to further investigate the underlying mechanism. BALB/c mice were
      challenged with OVA for the asthma model, which was validated by the changed
      levels of IL-4, IFN-gamma, and IgE. The elevation of IL-4 and the decreasing of
      IFN-gamma were significantly in middle (p<0.05) or high (p<0.01) paeonol dose
      groups compared with OVA group. MIP-1beta in bronchoalveolar lavage fluid (BALF)
      also decreased significantly in middle and high paeonol group compared with OVA
      group (p<0.01), which is similar to the change of its mRNA in lung tissues.
      Moreover, the inflammatory cells infiltration and collagen deposition were
      attenuated by paeonol and montelukast sodium via histology examination. At last
      the immune blot of the protein extracted from lung tissues demonstrated that
      paeonol decreased the expression of TLR4 and the nuclear translocation of NF
      kappaB, as well as the phosphorylation levels of P38 and ERK in asthma model. In
      conclusion, paeonol ameliorated OVA-induced asthma through the TLR4/NF-kappaB and
      mitogen-activated protein kinase (MAPK) signaling.

PMID- 30186354
TI  - Holistic Regulation of Angiogenesis with Chinese Herbal Medicines as a New Option
      for Coronary Artery Disease.
AB  - Effectively improving myocardial blood flow and controlling atherosclerotic
      plaque have always been key and difficult points in the prevention and treatment
      of coronary artery disease (CAD). Although "therapeutic angiogenesis" is regarded
      as a promising approach for ischemic heart disease by improving blood flow,
      angiogenesis itself can induce the destabilization of atherosclerotic plaque,
      which reflects the double-edged role of angiogenesis. Modulating the balance of
      angiogenesis can be an important target for CAD treatment. Traditional Chinese
      medicine (TCM) emphasizes the holistic view and dynamic balance of the body.
      Furthermore, the principle of activating blood circulation and removing blood
      stasis (ABCRS) is closely connected with angiogenesis and CAD. Recent research
      suggests that Chinese herbal medicines for ABCRS are effective in balancing the
      regulation of angiogenesis. This review presents the progress of recent research
      on the angiogenesis regulation with Chinese herbal medicines for ABCRS in CAD.
      Moreover, this review demonstrates that Chinese herbal medicines for ABCRS can
      not only promote angiogenesis in the ischemic area to improve myocardial blood
      flow but also alleviate angiogenesis to stabilize plaque in atherosclerosis,
      which reflects the holistic regulatory role in CAD treatment.

PMID- 30186355
TI  - Intracoronary Glycoprotein IIb/IIIa Inhibitors Improve Short-Term Mortality and
      Reinfarction in East Asian Patients with ST-Segment Elevation Myocardial
      Infarction after Thrombus Aspiration: A Meta-Analysis.
AB  - Objective: Intracoronary (IC) glycoprotein IIb/IIIa inhibitors (GPIs) after
      thrombus aspiration (TA) for patients with ST-segment elevation myocardial
      infarction (STEMI), as compared with percutaneous coronary interventions (PCI)
      alone, is still on debate. To address this issue, we performed a meta-analysis of
      results from prospective or randomized controlled trials on the topic. Methods:
      We searched electronic and printed sources (up to June 20, 2016) according to the
      selection criteria. Data were abstraction and meta-analysis was performed using
      RevMan 5.3 software. Results: The cohorts involved 14 articles describing 1,918
      participants were included. The incidence of the short-term major adverse cardiac
      events (MACE) was significantly reduced with intracoronary GPIs after TA (odds
      ratio [OR]: 0.29; 95% confidence interval [CI]: 0.13 to 0.65, p=0.003). Benefits
      were noted for short-term mortality (OR: 0.31; 95% CI: 0.17 to 0.57, p=0.0002)
      and reinfarction (OR: 0.28; 95% CI: 0.10 to 0.78, p=0.01) in subjects who
      received intracoronary GPIs after TA. Moreover, the Thrombolysis in Myocardial
      Infarction (TIMI) trial grade 3 postprocedure (OR: 2.29; 95% CI: 1.72 to 3.04,
      P<0.00001) and complete ST-segment resolution (STR) rate (OR: 2.68; 95% CI: 1.85
      to 3.87, P<0.00001) were both improved with intracoronary GPIs after TA. As a
      result, left ventricular ejection fraction (LVEF) at short-term follow-up showed
      a significant difference (OR: 7.33; 95% CI: 5.60 to 9.06, p<0.0001) in favor of
      the TA and intracoronary GPIs administration. Conclusions: Our study demonstrates
      that intracoronary GPIs may have a synergistic effect with thrombus aspiration on
      short-term mortality, reinfarction, and cardiac functional recovery.

PMID- 30186356
TI  - Effect of He's Santong Needling Method on Dysphagia after Stroke: A Study
      Protocol for a Prospective Randomized Controlled Pilot Trial.
AB  - Background: Dysphagia is a common complication of stroke, affecting up to 78% of
      stroke patients. The existence of dysphagia after stroke has been associated with
      an increased risk for pulmonary complications and even mortality. Previous
      studies have shown that acupuncture could be potential therapeutic method for
      treatment of dysphagia after stroke. A prospective randomized controlled pilot
      trial is designed to evaluate the effect of He's Santong needling method on
      dysphagia after stroke. Methods and Design: Sixty eligible participants will be
      recruited and randomly assigned into treatment group (He's Santong needling
      method and swallowing rehabilitation training) and control group (swallowing
      rehabilitation training) in a 1:1 ratio. All treatments will be provided everyday
      on weekdays with a two-day interval at the weekend, during a total treatment
      course of four weeks. The Penetration-Aspiration Scale with Fiberoptic Endoscopic
      Examination of Swallowing will be assessed at baseline and endpoint (Week 4) as
      primary outcomes. The Saitoh's classification score, Swallowing-Related Quality
      of Life score, the Modified Mann Assessment of Swallowing Ability score, and
      Surface Electromyography will be evaluated at baseline and endpoint as secondary
      outcomes. Ethics and Dissemination: The trial protocol has been approved by the
      Research Ethical Committee of Beijing Hospital of Traditional Chinese Medicine
      Affiliated to Capital Medical University on 9 May 2017 (ethical batch number:
      2017BL-013-02). Each participant will be notified regarding the study protocol.
      Written informed consent will be obtained from each participant. Trial
      Registration: ISRCTN registry: ISRCTN68981054; Registered on 25 September 2017.

PMID- 30186357
TI  - Effects of Juglans regia Root Bark Extract on Platelet Aggregation, Bleeding
      Time, and Plasmatic Coagulation: In Vitro and Ex Vivo Experiments.
AB  - Platelets have an important role in thrombosis and haemostasis. Hyperactivity of
      the platelets has been associated with thromboembolic diseases and represents the
      main cause of complications of cardiovascular diseases. Crude aqueous extract
      (CAE) of Juglans regia root bark was evaluated for bleeding time, antiaggregant
      activity by using agonists, thrombin, ADP, collagen, or arachidonic acid (in
      vitro and ex vivo), and anticoagulant activity by measuring the clotting
      parameters: activated partial thromboplastin time, prothrombin time, thrombin
      time, and fibrinogen dosage (in vitro and ex vivo). The result of this study
      reported that the strongest antiaggregant effect of CAE in vitro was observed on
      the ADP-induced aggregation with inhibitions up to 90 %, while, in ex vivo
      experiments, the inhibition (more than 80 %) was observed with all agonists.
      Anticoagulant effect of CAE significantly prolonged the TT and decreased the
      fibrinogen level in vitro and ex vivo without interfering with APTT and PT. The
      bleeding time in mice and rats was significantly increased by CAE. The
      antiplatelet and anticoagulant effect observed in this study suggest that Juglans
      regia could have antithrombotic and/or thrombolytic activities and provide an
      alternative therapy against thrombotic complications related to cardiovascular
      diseases.

PMID- 30186358
TI  - Effect of Edible Bird's Nest Extract on Lipopolysaccharide-Induced Impairment of
      Learning and Memory in Wistar Rats.
AB  - Cognitive disability is a common feature associated with a variety of
      neurological conditions including Alzheimer's Disease (AD), Parkinson's Disease
      (PD), brain injury, and stroke. Emerging evidence has demonstrated that
      neuroinflammation plays an important role in the development of cognitive
      impairment. Current available therapies are relatively ineffective in treating or
      preventing cognitive disabilities, thus representing an important, unfulfilled
      medical need. Hence, developing potential treatment is one of the major areas of
      research interest. Edible bird's nests (EBN) are nests formed by swiftlet's
      saliva containing sialic acid, which is believed to improve brain function. This
      present study was embarked upon to evaluate the learning and memory enhancing
      potential effect of EBN by using Morris water maze test in a Wistar rat model of
      LPS-induced neuroinflammation. LPS elicited cognitive impairment in the rats by
      significantly increasing the escape latency while decreasing the number of
      entries in the probe trial, which are coupled with increased production of
      proinflammatory cytokines (TNF-alpha, IL-1beta, and IL-6) and oxidative markers
      (ROS and TBARS) in the hippocampus. Treatment with EBN (125 mg/kg, 250 mg/kg, and
      500 mg/kg; p.o.) effectively reversed the effect of LPS on escape latency and
      probe trial and, in addition, inhibited the LPS-induced upregulation of
      proinflammatory cytokines and oxidative markers. These findings are suggestive
      that there is existence of neuroprotective effect contained inside the edible
      bird's nest.

PMID- 30186359
TI  - Immune response to influenza vaccination in the elderly is altered by chronic
      medication use.
AB  - Background: The elderly patient population is the most susceptible to influenza
      virus infection and its associated complications. Polypharmacy is common in the
      aged, who often have multiple co-morbidities. Previous studies have demonstrated
      that commonly used prescription drugs can have extensive impact on immune
      defenses and responses to vaccination. In this study, we examined how the
      dynamics of immune responses to the two influenza A virus strains of the
      trivalent inactivated influenza vaccine (TIV) can be affected by patient's
      history of using the prescription drugs Metformin, NSAIDs or Statins. Results: We
      provide evidence for differential antibody (Ab) production, B-cell phenotypic
      changes, alteration in immune cell proportions and transcriptome-wide
      perturbation in individuals with a history of long-term medication use, compared
      with non-users. We noted a diminished response to TIV in the elderly on
      Metformin, whereas those on NSAIDs or Statins had higher baseline responses but
      reduced relative increases in virus-neutralizing Abs (VNAs) or Abs detected by an
      enzyme-linked immunosorbent assay (ELISA) following vaccination. Conclusion:
      Collectively, our findings suggest novel pathways that might underlie how long
      term medication use impacts immune response to influenza vaccination in the
      elderly. They provide a strong rationale for targeting the medication-immunity
      interaction in the aged population to improve vaccination responses.

PMID- 30186360
TI  - DiNAR: revealing hidden patterns of plant signalling dynamics using Differential
      Network Analysis in R.
AB  - Background: Progress in high-throughput molecular methods accompanied by more
      complex experimental designs demands novel data visualisation solutions. To
      specifically answer the question which parts of the specifical biological system
      are responding in particular perturbation, integrative approach in which
      experimental data are superimposed on a prior knowledge network is shown to be
      advantageous. Results: We have developed DiNAR, Differential Network Analysis in
      R, a user-friendly application with dynamic visualisation that integrates
      multiple condition high-throughput data and extensive biological prior knowledge.
      Implemented differential network approach and embedded network analysis allow
      users to analyse condition-specific responses in the context of topology of
      interest (e.g. immune signalling network) and extract knowledge concerning
      patterns of signalling dynamics (i.e. rewiring in network structure between two
      or more biological conditions). We validated the usability of software on the
      Arabidopsis thaliana and Solanum tuberosum datasets, but it is set to handle any
      biological instances. Conclusions: DiNAR facilitates detection of network
      rewiring events, gene prioritisation for future experimental design and allows
      capturing dynamics of complex biological system. The fully cross-platform Shiny
      App is hosted and freely available at https://nib-si.shinyapps.io/DiNAR. The most
      recent version of the source code is available at https://github.com/NIB
      SI/DiNAR/ with a DOI 10.5281/zenodo.1230523 of the archived version in Zenodo.

PMID- 30186361
TI  - Fast Interleaved Multislice T1 Mapping: Model-Based Reconstruction of Single-Shot
      Inversion-Recovery Radial FLASH.
AB  - Purpose: To develop a high-speed multislice T1 mapping method based on a single
      shot inversion-recovery (IR) radial FLASH acquisition and a regularized model
      based reconstruction. Methods: Multislice radial k-space data are continuously
      acquired after a single nonselective inversion pulse using a golden-angle
      sampling scheme in a spoke-interleaved manner with optimized flip angles.
      Parameter maps and coil sensitivities of each slice are estimated directly from
      highly undersampled radial k-space data using a model-based nonlinear inverse
      reconstruction in conjunction with joint sparsity constraints. The performance of
      the method has been validated using a numerical and experimental T1 phantom as
      well as demonstrated for studies of the human brain and liver at 3T. Results: The
      proposed method allows for 7 simultaneous T1 maps of the brain at 0.5 * 0.5 * 4
      mm3 resolution within a single IR experiment of 4 s duration. Phantom studies
      confirm similar accuracy and precision as obtained for a single-slice
      acquisition. For abdominal applications, the proposed method yields three
      simultaneous T1 maps at 1.25 * 1.25 * 6 mm3 resolution within a 4 s breath hold.
      Conclusion: Rapid, robust, accurate, and precise multislice T1 mapping may be
      achieved by combining the advantages of a model-based nonlinear inverse
      reconstruction, radial sampling, parallel imaging, and compressed sensing.

PMID- 30186362
TI  - Qualitative and Sensitivity Analysis of the Effect of Electronic Cigarettes on
      Smoking Cessation.
AB  - Recently, the role of the electronic cigarettes (e-cigarettes) in a way to reduce
      smoking is increasing. E-cigarettes are a device that delivers only the nicotine,
      and its use is considered less harmful to health compared with tobacco
      cigarettes. Smokers frequently make use of e-cigarettes as one of the nonsmoking
      aid devices. In this work, we propose a mathematical model to analyze the effect
      of e-cigarettes on smoking cessation. The stability and the bifurcation of the
      model have been discussed. The parameter estimations from the observed data are
      drawn, and using the parameters, a reasonable smoking model has been designed.
      Moreover, by considering the sensitivity results depending on the basic
      reproduction number R0, the effective strategies that reduce the smokers are
      investigated. Numerical simulations of the model show that e-cigarettes may
      somewhat diminish the numbers of smokers, but it does not reduce the number of
      quitters ultimately.

PMID- 30186363
TI  - Impact of symptoms by gender and age in Japanese subjects with irritable bowel
      syndrome with constipation (IBS-C): a large population-based internet survey.
AB  - Background: Irritable bowel syndrome with constipation (IBS-C) is a
      representative psychosomatic disorder. Several pathophysiological factors have
      been linked to IBS symptoms such as the modulation of gastrointestinal motility,
      visceral hypersensitivity, dysregulation of the gut-brain axis, genetic and
      environmental factors, sequelae of infection, and psychosocial disorders. It is
      likely that biopsychosocial aspects of IBS-C underlie its gender and age effects.
      However, the influence of each symptom of IBS-C by gender and age is not well
      understood. We hypothesized that the expression rate of each IBS-C symptom in
      females and in subjects aged 20-49 years was higher than that of subjects who
      were male and aged 50-79 years. Methods: We conducted an internet survey of
      30,000 adults from the general Japanese population. IBS-C subjects were asked to
      answer a questionnaire on the degree of anxiety, thoughts about bowel habits, and
      their dominant gastrointestinal symptoms together with exacerbation factors. The
      correlation between gender and age and IBS-C symptoms was analyzed. Results: When
      analyzed by gender, the expression rate of abdominal discomfort, abdominal
      distention, and abdominal fullness was significantly higher in female than male
      IBS-C subjects (66.5% vs. 58.7%, p < 0.05; 54.7% vs. 43.6%, p < 0.01; 18.9% vs.
      9.6%, p < 0.01, respectively). When analyzed by age, the expression rate of
      abdominal distention and abdominal pain was significantly higher among IBS-C
      subjects aged 20-49 years than those aged 50-79 years (55.7% vs. 46.8%, p < 0.05;
      36.6% vs. 20.6%, p < 0.001, respectively). In contrast, there was no gender or
      age differences with regard to the most common and bothersome symptom (abdominal
      bloating) among IBS-C subjects. Conclusions: The expression rate of some IBS-C
      symptoms was higher among females and those aged 20-49 years than males and those
      aged 50-79 years, respectively. It is important to understand the impact of
      symptoms by gender and age to evaluate the pathology of IBS-C from a
      biopsychosocial perspective. Trial registration: Although this survey was an
      anonymous internet survey, we obtained informed consent for the study as an
      online response. The disclosure of this study was approved by the Ethics
      Committee of Tohoku University Graduate School of Medicine (approval number: 2015
      1-405).

PMID- 30186364
TI  - Configuration Synthesis and Performance Analysis of Finger Soft Actuator.
AB  - Compared with the traditional rigid finger actuator, the soft actuator has the
      advantages of light weight and good compliance. This type of finger actuator can
      be used for data acquisition or finger rehabilitation training, and it has broad
      application prospects. The motion differences between the soft actuator and
      finger may cause extrusion deformation at the binding point, and the binding
      forces along nonfunctional direction may reduce drive efficiency. In order to
      reduce the negative deformation of soft structure and improve comfort, the
      configuration synthesis and performance analysis of the finger soft actuator were
      conducted for the present work. The configuration synthesis method for soft
      actuator was proposed based on the analysis of the physiological structure of the
      finger, and the soft actuator can make the human-machine closed-loop structure
      including n joints (n = 1, 2, 3) meet the requirement of DOF (degrees of
      freedom). Then the typical feasible configurations were enumerated. The different
      typical configurations were analyzed and compared based on the establishment of
      mathematical models and simulation analysis. Results show that the configuration
      design method is feasible. This study offers a theoretical basis for designing
      the configuration of finger soft actuator.

PMID- 30186365
TI  - Hydrogenation of CO2 at ambient pressure catalyzed by a highly active
      thermostable biocatalyst.
AB  - Background: Replacing fossil fuels as energy carrier requires alternatives that
      combine sustainable production, high volumetric energy density, easy and fast
      refueling for mobile applications, and preferably low risk of hazard. Molecular
      hydrogen (H2) has been considered as promising alternative; however, practical
      application is struggling because of the low volumetric energy density and the
      explosion hazard when stored in large amounts. One way to overcome these
      limitations is the transient conversion of H2 into other chemicals with increased
      volumetric energy density and lower risk hazard, for example so-called liquid
      organic hydrogen carriers such as formic acid/formate that is obtained by
      hydrogenation of CO2. Many homogenous and heterogenous chemical catalysts have
      been described in the past years, however, often requiring high pressures and
      temperatures. Recently, the first biocatalyst for this reaction has been
      described opening the route to a biotechnological alternative for this
      conversion. Results: The hydrogen-dependent CO2 reductase (HDCR) is a highly
      active biocatalyst for storing H2 in the form of formic acid/formate by
      reversibly catalyzing the hydrogenation of CO2. We report the identification,
      isolation, and characterization of the first thermostable HDCR operating at
      temperatures up to 70  degrees C. The enzyme was isolated from the thermophilic
      acetogenic bacterium Thermoanaerobacter kivui and displays exceptionally high
      activities in both reaction directions, substantially exceeding known chemical
      catalysts. CO2 hydrogenation is catalyzed at mild conditions with a turnover
      frequency of 9,556,000 h-1 (specific activity of 900 umol formate min-1 mg-1) and
      the reverse reaction, H2 + CO2 release from formate, is catalyzed with a turnover
      frequency of 9,892,000 h-1 (930 umol H2 min-1 mg-1). The HDCR of T. kivui
      consists of a [FeFe] hydrogenase subunit putatively coupled to a tungsten
      dependent CO2 reductase/formate dehydrogenase subunit by an array of iron-sulfur
      clusters. Conclusions: The discovery of the first thermostable HDCR provides a
      promising biological alternative for a chemically challenging reaction and might
      serve as model for the better understanding of catalysts able to efficiently
      reduce CO2. The catalytic activity for reversible CO2 hydrogenation of this
      enzyme is the highest activity known for bio- and chemical catalysts and
      requiring only ambient temperatures and pressures. The thermostability provides
      more flexibility regarding the process parameters for a biotechnological
      application.

PMID- 30186366
TI  - Reducing risk of Clostridium difficile infection and overall use of antibiotic in
      the outpatient treatment of urinary tract infection.
AB  - Background: Risk of community-acquired Clostridium difficile infection (CA-CDI)
      following antibiotic treatment specifically for urinary tract infection (UTI) has
      not been evaluated. Methods: We conducted a nested case-control study at Kaiser
      Permanente Northern California, 2007-2010, to assess antibiotic prescribing and
      other factors in relation to risk of CA-CDI in outpatients with uncomplicated
      UTI. Cases were diagnosed with CA-CDI within 90 days of antibiotic use. We used
      matched controls and confirmed case-control eligibility through chart review.
      Antibiotics were classified as ciprofloxacin (most common), or low risk
      (nitrofurantoin, sulfamethoxazole/trimethoprim), moderate risk, or high risk
      (e.g. cefpodoxime, ceftriaxone, clindamycin) for CDI. We computed the adjusted
      odds ratios (ORs) and 95% confidence intervals (CIs) for the relationship of
      antibiotic treatment for uncomplicated UTI and history of relevant
      gastrointestinal comorbidity (including gastrointestinal diagnoses, procedures,
      and gastric acid suppression treatment) with risk of CA-CDI using logistic
      regression analysis. Results: Despite the large population, only 68 cases were
      confirmed with CA-CDI for comparison with 112 controls. Female sex [81% of
      controls, adjusted odds ratio (OR) 6.3, CI 1.7-24), past gastrointestinal
      comorbidity (prevalence 39%, OR 2.3, CI 1.1-4.8), and nongastrointestinal
      comorbidity (prevalence 6%, OR 2.8, CI 1.4-5.6) were associated with increased CA
      CDI risk. Compared with low-risk antibiotic, the adjusted ORs for antibiotic
      groups were as follows: ciprofloxacin, 2.7 (CI 1.0-7.2); moderate-risk
      antibiotics, 3.6 (CI 1.2-11); and high-risk antibiotics, 11.2 (CI 2.4-52).
      Conclusions: Lower-risk antibiotics should be used for UTI whenever possible,
      particularly in patients with a gastrointestinal comorbidity. However, UTI can be
      managed through alternative approaches. Research into the primary prevention of
      UTI is urgently needed.

PMID- 30186367
TI  - Renal trauma: the current best practice.
AB  - The kidneys are the most vulnerable genitourinary organ in trauma, as they are
      involved in up to 3.25% of trauma patients. The most common mechanism for renal
      injury is blunt trauma (predominantly by motor vehicle accidents and falls),
      while penetrating trauma (mainly caused by firearms and stab wound) comprise the
      rest. High-velocity weapons impose specifically problematic damage because of the
      high energy and collateral effect. The mainstay of renal trauma diagnosis is
      based on contrast-enhanced computed tomography (CT), which is indicated in all
      stable patients with gross hematuria and in patients presenting with microscopic
      hematuria and hypotension. Additionally, CT should be performed when the
      mechanism of injury or physical examination findings are suggestive of renal
      injury (e.g. rapid deceleration, rib fractures, flank ecchymosis, and every
      penetrating injury of the abdomen, flank or lower chest). Renal trauma management
      has evolved during the last decades, with a distinct evolution toward a
      nonoperative approach. The lion's share of renal trauma patients are managed
      nonoperatively with careful monitoring, reimaging when there is any
      deterioration, and the use of minimally invasive procedures. These procedures
      include angioembolization in cases of active bleeding and endourological stenting
      in cases of urine extravasation.

PMID- 30186368
TI  - Abiraterone in chemotherapy-naive patients with metastatic castration-resistant
      prostate cancer: a systematic review of 'real-life' studies.
AB  - Background: To assess the efficacy and safety of treatment with abiraterone
      acetate (AA) in chemotherapy-naive men with metastatic castration-resistant
      prostate cancer (mCRPC) in the 'real-life' setting. Methods: Data acquisition on
      the outcomes of the use of AA in chemotherapy-naive patients with mCRPC was
      performed by a MEDLINE comprehensive systematic literature search using
      combinations of the following key words: 'prostate cancer', 'metastatic',
      'castration resistant', 'abiraterone', 'real life', and excluding controlled
      clinical trials (phase II and III studies). Identification and selection of the
      studies was conducted according to the Preferred Reporting Items for Systematic
      Reviews and Meta-analysis (PRISMA) criteria. Outcomes of interest were overall
      survival (OS), progression-free survival (PFS), 12-week 50% reduction in prostate
      specific antigen (PSA), and grade 3 and higher adverse events. Data were
      narratively synthesized in light of methodological and clinical heterogeneity.
      Results: Within the eight identified studies that fulfilled the criteria, a total
      of 801 patients were included in the meta-analysis. Baseline PSA ranged between
      9.5 and 212.0 ng/ml. Most of the patients had bone metastases. Duration of
      treatment with AA was longer in the studies with lower baseline PSA levels. The
      median OS ranged between 14 and 36.4 months. The PFS, assessed according to
      different definitions, ranged from 3.9 to 18.5 months. A 50% PSA reduction at 12
      weeks was reached by a variable percentage of patients ranging from 36.0% to
      62.1%. Finally, the rate of grade 3 and higher adverse events was reported in
      three studies and ranged from 4.4% to 15.5%. Conclusions: Despite the high grade
      of heterogeneity among studies, treatment with AA seems to ensure good survival
      outcomes in the 'real-life' setting. However, prospective studies based on
      patients' characteristics being more similar to 'real-life' patients are
      necessary.

PMID- 30186370
TI  - BESS Fellowships and Prizes 2018.

PMID- 30186369
TI  - Self-reported social and activity restrictions accompany local impairments in
      posterior tibial tendon dysfunction: a systematic review.
AB  - Background: Posterior tibial tendon dysfunction (PTTD) is a painful, progressive
      tendinopathy that reportedly predominates in middle-age, overweight women. There
      is no evidence based guidelines that clinicians can use to guide treatment
      planning, which leaves clinicians to make decisions on the basis of presenting
      clinical impairments and self-reported pain and disability. The purpose of this
      systematic review was to quantify clinical impairments, pain and disability in
      individuals with PTTD compared with controls. Methods: Five databases were
      searched for terms referring to the posterior tibial tendon and flatfoot up to
      and including 11 March 2018. The systematic review was registered with PROSPERO
      (CRD: 42016046951). Studies were eligible if they were published in the English
      language and contained data on clinical impairments, pain or disability compared
      between participants diagnosed with PTTD and pain-free individuals. Standardised
      mean differences (SMDs) were calculated where possible and meta-analysis was
      performed when homogeneity of outcomes allowed. Results: Ten eligible studies
      were identified and pooled in the meta-analyses. Strong effects were revealed for
      poor heel rise endurance (SMD -1.52, 95% CI -2.05 to - 0.99), less forefoot
      adduction-inversion strength (SMD -1.19, 95% CI -1.68 to - 0.71) and lower arch
      height (SMD -1.76, 95% CI -2.29 to - 1.23). Compared to controls, individuals
      with PTTD also had more self-reported stiffness (SMD 1.45, 95% CI 0.91 to 1.99),
      difficulties caused by foot problems (SMD 1.42, 95% CI 0.52 to 2.33) and social
      restrictions (SMD1.26, 95% CI 0.25 to 2.27). Conclusion: There is evidence of
      impaired tibialis posterior capacity and lowered arch height in individuals with
      PTTD compared to controls. Further to addressing the expected impairments in
      local tendon function and foot posture, pain, stiffness, functional limitations
      and social participation restrictions should be considered when managing PTTD.

PMID- 30186371
TI  - Associations among inflammation, mental health, and quality of life in adults
      with metabolic syndrome.
AB  - Background: Metabolic syndrome (MetS), a pro-inflammatory state, has become
      increasingly common worldwide and is a major risk factor for type 2 diabetes
      mellitus and cardiovascular disease. Recently, studies on the relationships among
      inflammation, mental health, quality of life, and other diseases have been
      conducted. Methods: We investigated the relationship between serum high
      sensitivity C-reactive protein (hs-CRP) levels, as an indicator of inflammation,
      and the quality of life and psychiatric symptoms of Korean adults with MetS. The
      analysis used data from the Korean National Health and Nutrition Examination
      Survey, a cross-sectional survey of Korean civilians conducted from January to
      December 2015. Data from 1600 participants were analyzed in this study. Quality
      of life was assessed using the EuroQol 5-dimension (EQ-5D) instrument. Results:
      Serum hs-CRP levels showed a significant inverse correlation with the EQ-5D index
      of the overall quality of life. High serum hs-CRP levels were positively
      associated with mobility problems and suicidal ideation in adults with MetS
      (multivariate-adjusted odds ratio [OR] 1.66, 95% confidence interval [CI] 1.03
      2.66, p = 0.036; and multivariate-adjusted OR 2.48, 95% CI 1.23-4.99, p = 0.011).
      Conclusions: These findings suggest that the elevated inflammatory status in MetS
      is associated with decreased quality of life and mental health problems. Further
      prospective studies are needed to confirm the impact of inflammation on the
      quality of life and mental health of adults with MetS.

PMID- 30186372
TI  - Effectiveness of educational intervention based on psychological factors on
      achieving health outcomes in patients with type 2 diabetes.
AB  - Background: Managing type 2 diabetes (T2D) is assumed to be heavily dependent on
      patients' active participation in their own self-care behaviors including
      prescribed diets. Objectives: The purpose of the present study was to investigate
      the effectiveness of educational intervention based on psychological factors on
      nutritional behaviors as well as levels of fasting blood sugar (FBS) and glycated
      hemoglobin (HbA1c) in patients with T2D referring to diabetes clinics and
      healthcare centers in the city of Izeh, Iran. Methods: A total number of 145
      patients were recruited in this clinical trial and then randomly assigned to two
      groups of intervention (n = 73 individuals) and control (n = 72 individuals).
      After that, a researcher-made multi-part questionnaire including a demographic
      characteristics information form, a nutritional perceptions and beliefs
      questionnaire; a scale measuring fears, concerns, and discomforts associated with
      diabetic diet, as well as the valid and reliable Perceived Dietary Adherence
      Questionnaire were used to collect the required data before and 3 months after
      the completion of the educational intervention. To this end, the patients in the
      intervention group attended an educational program for eight sessions but the
      individuals in the control group only received routine services. Data analysis
      was also conducted using the SPSS Statistics (Version 18) and via descriptive and
      inferential statistics. Results: The findings revealed that the mean scores of
      the sub-groups of nutritional perceptions and beliefs (but not exaggerated ones)
      in the patients assigned to the intervention group were significantly higher than
      those in the control group after 3 months (p = 0.001). As well, the mean scores
      of the sub-groups of fears, concerns, and discomforts in patients as well as
      exaggerated beliefs witnessed a significant decrease in the intervention group
      compared to those in the control group (p = 0.001) 3 months after the educational
      intervention. Furthermore, the mean scores of adherence to a healthy diet in the
      intervention group had significantly increased compared to those in the control
      group. There was correspondingly a significant descending trend in the average
      levels of fasting blood sugar (FBS) and glycated hemoglobin (HbA1c) in the
      intervention group compared to those obtained in the control group (p = 0.001).
      Conclusion: The results of this study shed light on the importance of the
      effectiveness of psychological factors on achieving health outcomes in patients
      with type 2 diabetes (T2D). Moreover, a new combination of diet-related
      psychological factors in patients with diabetes was introduced in the present
      study.Trial registration IRCT. IRCT20180308039008N1. Registered 15 April 2018,
      http://www.irct.ir.

PMID- 30186373
TI  - Advances in CLARITY-based tissue clearing and imaging.
AB  - CLARITY is a novel tissue clearing technique that transforms intact biological
      tissues into a nanoporous hydrogel-tissue hybrid, preserving anatomical
      structures, proteins and nucleic acids. The hydrogel-based structure is
      transparent after the removal of lipids and permits several rounds of
      immunostaining and imaging. This technique provides an ideal way for researchers
      to examine the central nervous system (i.e., mouse brain and spinal cord) intact.
      CLARITY was selected as one of ten breakthroughs in 2013 by Science. However, the
      original CLARITY technique still has severe technical limitations which impede
      its application in wider fields. Therefore, many modified clearing methods based
      on CLARITY have emerged. As all CLARITY-based tissue clearing techniques involve
      similar procedures, the present review attempted to divide these methods into
      individual procedures in order to provide new ways to test and combine tissue
      clearing methods. Furthermore, the combination of clearing methods could help to
      determine the optimal method for clearing and imaging large samples.

PMID- 30186375
TI  - Combined antitumor effects of P-5m octapeptide and 5-fluorouracil on a murine
      model of H22 hepatoma ascites.
AB  - The present study has demonstrated that P-5m octapeptide (P-5m) has therapeutic
      potential in metastatic human hepatocarcinoma, possibly through the modulation of
      matrix metalloproteinase-2 expression. The purpose of the present study was to
      evaluate the antitumor effect of P-5m combined with 5-fluorouracil (5-Fu) on the
      treatment of hepatoma 22 (H22) hepatocarcinoma malignant ascites in a mouse
      model. The inhibitory effect on the growth of mouse ascites tumors was monitored
      by measuring body weight gain, survival time, ascites volume, numbers of tumor
      cells, DNA synthesis and peritoneal capillary permeability analysis. The present
      data revealed a significant reduction in ascites volume and cell count in mice
      that were treated with P-5m plus 5-Fu. Furthermore, the median survival time in
      mice in the combination group was prolonged compared with the disease control
      group. Moreover, a significant reduction in the total H22 ascites cell count in
      mice from the combination group was observed when compared with the disease
      control group. P-5m plus 5-Fu was able to induce the cell cycle arrest and
      inhibit the peritoneal capillary permeability of the mice. To conclude, the
      present study indicated that P-5m may have therapeutic potential in ascites
      caused by hepatocellular carcinoma.

PMID- 30186376
TI  - Evaluation of the safety of MRI scans in patients undergoing dual-chamber
      pacemaker implantation.
AB  - The safety of magnetic resonance imaging (MRI) scans in patients undergoing dual
      chamber pacemaker (Medtronic's EnRhythm MRI SureScan IPG (implantable pulse
      generator) and CapSureFix MRI pacing electrodes) implantation were evaluated. A
      total of 86 patients undergoing this pacemaker implantation who were admitted to
      Huanggang Hospital from June 2006 to March 2017 were continuously selected. On
      average 6.8+/-2.3 months after the implantation, the first MRI scan was
      conducted. The mean scan time was 2.2+/-0.9 and mean duration was 45.6+/-12.3
      min; mean follow-up visit period was 40.5+/-15.6 months, and after follow-up, all
      the abnormal symptoms of patients and pacemaker abnormalities after scans were
      recorded. Causes of receiving MRI scans included neurological diseases (27%),
      spinal diseases (14%), cancers (26%), joint injuries (25%) and visceral systems
      (8%). A total of 12 cases (14.0%) showed significant discomfort symptoms, 10
      cases (11.6%) showed pacemaker abnormalities, and the incidence rate was 25.6%.
      Multivariate logistic regression analysis showed that the basic types of
      cardiovascular diseases, dependence on pacemakers, duration of education, pacing
      threshold, impedance and MRI scan time were related to the occurrence of adverse
      scan results (p<0.05). In conclusion, MRI scans show that MRI-compatible dual
      chamber pacemaker was relatively safe.

PMID- 30186374
TI  - Fluorescent contrast agents for tumor surgery.
AB  - Cancer is a leading cause of cases of mortality worldwide. The most effective
      method to cure solid tumors is surgery. Every year, >50% of cancer patients
      receive surgery to remove solid tumors. Surgery may increase the cure rate of
      most solid tumors by 4-11 fold. Surgery has many challenges, including
      identifying small lesions, locating metastases and confirming complete tumor
      removal. Fluorescence guidance describes a new approach to improve surgical
      accuracy. Near-infrared fluorescence imaging allows for real-time early diagnosis
      and intraoperative imaging of lesion tissue. The results of previous preclinical
      studies in the field of near-infrared fluorescence imaging are promising. This
      review provides examples introducing the three kinds of fluorescent dyes: The
      passive fluorescent dye indocyanine green, which has been approved by the Food
      and Drug Administration for clinical use in the USA, the fluorescent prodrug 5
      aminolevulinic acid, a porphyrin precursor in the heme synthesis, and biomarker
      targeted fluorescent dyes, which allow conjugation to different target sites.

PMID- 30186377
TI  - Use of ozonated water as a new therapeutic approach to solve current concerns
      around antitumor treatment.
AB  - Tumor hypoxia is a severe problem affecting tumor therapy because it reduces the
      sensitivity of chemotherapy and radiation therapy. Ozone has been known to
      improve peripheral blood perfusion and oxygen partial pressure. The effect of
      ozonated water on tumor hypoxia, alone and in combination with an antitumor drug
      was studied in the present study. Following intraperitoneal administration of
      ozonated water to colon-26-bearing mice, the Hoechst 33342-positive area and the
      intratumoral oxygen partial pressure was significantly increased. The tumor
      growth rate was more suppressed when ozonated water was combined with cisplatin
      (CDDP) compared with CDDP treatment alone. The number of Ki-67-positive cells
      significantly decreased, whereas the number of TUNEL-positive cells significantly
      increased. The present study showed that ozonated water increased intratumoral
      blood perfusion and improved tumor hypoxia. In addition, ozonated water increased
      the therapeutic effect of CDDP. These findings, as well as previous reports,
      suggest that tumor growth is suppressed after treatment with ozonated water as
      the amount of CDDP reaching the tumor is increased when the intratumoral blood
      perfusion is increased due to the ozonated water. Thus, the administration of
      ozonated water may be a new therapeutic approach to solve current concerns
      regarding antitumor treatment.

PMID- 30186378
TI  - Efficacy, functional outcome and post-operative complications of total abdominal
      colectomy with ileorectal anastomosis vs. segmental colectomy in hereditary non
      polyposis colorectal cancer.
AB  - The primary objective of the present study was to compare the choice of
      colectomy, i.e. total vs. segmental colectomy, in cases of hereditary non
      polyposis colorectal cancer (HNPCC/lynch syndrome), and to assess the efficacy,
      oncological safety, functional outcome and post-operative complications of total
      abdominal colectomy with ileorectal anastomosis vs. segmental colectomy in HNPCC.
      A total of 289 patients who fulfilled the Amsterdam I and II criteria for HNPCC
      were included in the present study. The criteria for confirmation of the
      diagnosis were five micro-satellite markers, namely BAT25, BAT26, D2s123, d5S346
      and D17S250. Group 1 included those patients who received their diagnosis in the
      years 2011-2013 and those in group 2 had been diagnosed in the years 2014-2016.
      The cohort had been subjected to two different types of surgery: i) Standard and
      extended surgery including total colectomy with ileal pouch anal anastomosis and
      subtotal colectomy and ii) segmental resection of the colon. Analysis of patient
      data indicated that in group 1, the extended resection was performed more
      frequently than in group 2 (68 vs. 34% of cases) and accordingly, segmental
      resection was less frequent (32 vs. 66%; P<0.001). In conclusion, the extensive
      rather than the segmental resection has been commonly performed several years
      ago, but at present, the surgical method of choice in cases of lynch syndrome is
      segmental resection. Trial registry no. QU/MR2011/CRC5, dated 21 March 2011.

PMID- 30186379
TI  - Microarray data analysis to identify differentially expressed genes and
      biological pathways associated with asthma.
AB  - The present study aimed to identify differentially expressed genes (DEGs) and
      biological processes (BPs) associated with asthma. DEGs between allergic asthma
      and healthy controls were screened from GSE15823. Gene Ontology and Kyoto
      Encyclopedia of Genes and Genomes pathway enrichment analyses were performed
      using Database for Annotation, Visualization and Integrated Discovery. A protein
      protein interaction network was constructed, followed by module mining and
      functional analysis. Additionally, GSE41649 was downloaded to validate the
      reliability of the results. In GSE41649, DEGs were identified and compared with
      key DEGs identified in GSE15823. A total of 43 upregulated and 275 downregulated
      DEGs were obtained from GSE15823. Upregulated DEGs, such as nitric oxide synthase
      2 (NOS2), were enriched in BPs related to oxidation reduction. Downregulated
      DEGs, such as chemokine (C-C motif) ligand 19 (CCL21) and Cys-X-Cys ligand
      (CXCL9), were enriched in immune response-related BPs. Protein tyrosine
      phosphatase receptor type C (PTPRC), CCL21, and CXCL9 were identified as hub
      genes. The DEGs in module 1 were significantly involved in the chemokine
      signaling pathway (P<0.05). The expression of the key genes obtained in GSE15823
      demonstrated the same variation directions in the two datasets. The immune
      response, oxidants and nitric oxide metabolic pathways may have important roles
      in the progression of asthma. DEGs of PTPRC, CCL21, CXCL9 and NOS2 may be the
      potential targets for asthma diagnosis and treatment.

PMID- 30186380
TI  - HOXD10 silencing suppresses human fibroblast-like synoviocyte migration in
      rheumatoid arthritis via downregulation of the p38/JNK pathway.
AB  - Homeobox D10 (HOXD10) belongs to the human homeobox (HOX) gene family, and the
      homologous protein encoded by HOX primarily controls cell differentiation and
      morphogenesis during embryonic development. The current study aimed to explore
      the roles and mechanisms of HOXD10 in the migration of human fibroblast-like
      synoviocytes in rheumatoid arthritis (RAFLS). Cell counting kit-8, cell migration
      and wound healing assays were performed to examine the cell viability and
      migration, respectively. Western blot and reverse transcription-quantitative
      polymerase chain reaction assays were used to evaluate the association between
      mRNA and protein expression levels. The results revealed HOXD10 expression was
      upregulated in tissues from patients with RA. HOXD10 silencing inhibited the
      viability of RAFLS. In addition, HOXD10 silencing suppressed the migration of
      RAFLS through modulating the expression of cadherin-11, N-cadherin, E-cadherin,
      vimentin, zonula occludens-1, integrinbeta1 and paxillin. In conclusion, HOXD10
      silencing downregulates the p38/c-Jun N-terminal kinase signaling pathway, which
      in turn may suppress the migration of RAFLS.

PMID- 30186381
TI  - MicroRNA-138 inhibits SOX12 expression and the proliferation, invasion and
      migration of ovarian cancer cells.
AB  - The aim of the present study was to investigate the expression and biological
      functions of microRNA (miR)-138 in ovarian cancer at the tissue and cellular
      levels, as well as its underlying mechanisms. A total of 47 patients with ovarian
      cancer were included in the present study. Ovarian cancer tissues were subjected
      to staging classification according to the FIGO 2000 criteria. Lymphatic
      metastasis was also examined. Ovarian cancer A2780 cells were transfected using
      liposomes. Reverse transcription-quantitative polymerase chain reaction was used
      to measure the expression of miR-138. A Cell-Counting Kit 8 assay was used to
      examine cell viability, while a Transwell assay was employed to study cell
      invasion and migration. The effects of miR-138 on SOX12 protein expression were
      examined by western blot analysis. A dual luciferase reporter assay was performed
      to identify the direct interaction between miR-138 and SOX12 gene. Expression of
      miR-138 was downregulated in ovarian cancer tissues. The level of miR-138 in
      patients with ovarian cancer with lymphatic metastasis was significantly lower
      compared with patients without lymphatic metastasis. However, expression of miR
      138 was not associated with the stage of ovarian cancer. Upregulation of miR-138
      inhibited the proliferation and suppressed the invasion and migration of A2780
      cells. SOX12 promoted the proliferation, invasion and migration of A2780 cells.
      In addition, miR-138 downregulated the expression of SOX12 via binding with the
      3'-UTR of SOX12 gene. The present study demonstrates that miR-138 expression is
      downregulated in ovarian cancer tissues and miR-138 acts as a tumor suppressor
      gene by inhibiting SOX12 expression and the proliferation, invasion and migration
      of ovarian cancer cells.

PMID- 30186382
TI  - Preparation and characterization of norcantharidin liposomes modified with
      stearyl glycyrrhetinate.
AB  - In the current study, norcantharidin (NCTD)-loaded liposomes (LIPs) modified with
      stearyl glycyrrhetinate (SG; SG-NCTD-LIP) were prepared by the ethanol injection
      method. To increase the drug encapsulation efficiency (EE), the formulation of
      NCTD-LIP was optimized by single factor test and orthogonal design. The release
      of NCTD in vitro from SG-NCTD-LIP was evaluated by equilibrium dialysis. The
      cytotoxicity of SG-NCTD-LIP in HepG2 was investigated by MTT assay. The results
      revealed that the EE of liposomes was ~27.80%, the average SG-NCTD-LIP was 87.5
      nm, the in vitro NCTD release from SG-NCTD-LIP was delayed compared with NCTD in
      solution and the drug-release kinetic followed a first-order model. MTT assays
      revealed increased cytotoxicity activity against HepG2 cells for SG-NCTD-LIP
      compared with free NCTD. In conclusion, SG-NCTD-LIP prepared in the present study
      may be a promising liposomal drug delivery system for anticancer drugs in liver
      targeting therapy.

PMID- 30186383
TI  - Effect of naproxen on proliferation and differentiation of primary cell cultures
      isolated from human cartilage tissue.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) that are applied through oral,
      injectable or topical routes have been widely used in painful and inflammatory
      musculoskeletal diseases. The current study aimed to determine whether naproxen,
      an aryl acetic acid derivative with analgesic and anti-inflammatory effects, has
      a toxic effect on human chondrocytes. Samples containing monolayer primary
      chondrocyte cultures were prepared following resection from osteochondral tissues
      obtained from patients with gonarthrosis. Cell viability, toxicity and
      proliferation and levels of stage-specific embryonic antigen-1, a precursor to
      human prechondrocytes, were evaluated spectrophotometrically. The results from
      the untreated control group were compared with those of the study groups, where
      naproxen was administered in varying doses (1-1,000 uM). Surface morphologies of
      the cells were compared using inverted light and environmental scanning electron
      microscopy. Treatment groups were compared by analysis of variance with Tukey's
      honest difference post hoc test. P<0.01 was considered to indicate a
      statistically significant difference. The research revealed significant changes
      to proliferation and differentiation of chondrocytes in all treatment groups
      (P<0.01). Naproxen was demonstrated to suppress chondrocyte proliferation and
      differentiation, which may be an important factor to consider when prescribing
      this medication to patients.

PMID- 30186384
TI  - Combination therapy with BMP-2 and psoralen enhances fracture healing in
      ovariectomized mice.
AB  - The advantages of combining local delivery of bone morphogenetic protein (BMP)-2
      with systemic or local anti-osteoporosis treatments have also been studied for
      enhancing osteoporotic fracture healing. The aim of the present study was to
      evaluate the effect of combination therapy with BMP-2 and psoralen on fracture
      repair in ovariectomized mice. At 6 weeks after bilateral ovariectomy, mice
      (n=30) underwent unilateral transverse osteotomy on the femur and were divided
      into 3 groups. In the model group (n=10), animals were implanted with an
      absorbable collagen sponge (ACS) alone and administered physiological saline
      intragastrically (i.g.). In the recombinant human (rh)BMP-2 group (n=10), animals
      were implanted with an ACS loaded with 2.5 ug rhBMP-2 and administered
      physiological saline i.g. In the psoralen + rhBMP-2 group (n=10) animals were
      implanted with an ACS loaded with 2.5 ug rhBMP-2 and administered psoralen i.g.
      The mice were euthanized after 21 days and their fractured femurs were assessed
      by micro computed tomography, histological analysis and biomechanical testing.
      Furthermore, the serum of the animals was analyzed. Psoralen + rhBMP-2 exerted
      more beneficial effects on callus consolidation and biomechanical strength. In
      addition, increased bone-specific alkaline phosphatase levels and decreased C
      terminal telopeptide of type-1 collagen were observed in the Psoralen + rhBMP-2
      group. However, no difference in estrogen levels was detected between the groups.
      In conclusion, the present study demonstrated that in ovariectomized mice,
      combination of locally delivered BMP-2 and systemically administered psoralen
      improved bone healing compared with BMP-2 alone.

PMID- 30186385
TI  - MicroRNA-101-3p inhibits proliferation in retinoblastoma cells by targeting EZH2
      and HDAC9.
AB  - Retinoblastoma is the most frequent intraocular malignant tumor type to occur in
      childhood. MicroRNA (miR)-101-3p has been reported to function as a tumor
      suppressor in various types of cancer. However, the biological function and
      underlying mechanisms of miR-101-3p in retinoblastoma are largely unknown. In the
      present study, it was identified that miR-101-3p was downregulated in
      retinoblastoma. MTT and flow cytometry assays demonstrated that ectopic
      overexpression of miR-101-3p significantly inhibited cell viability and cell
      cycle progression in WERI-Rb-1 and Y79 cells. In vivo mouse experiments further
      confirmed the anti-proliferative role of miR-101-3p in retinoblastoma.
      Additionally, predictions with TargetScan software indicated that the 3'
      untranslated regions of enhancer of zeste homolog 2 (EZH2) and histone
      deacetylase (HDAC9) mRNAs are targeted by miR-101-3p. Accordingly, a dual
      luciferase reporter gene assay demonstrated that miR-101-3p directly targeted
      EZH2 and HDAC9 to suppress the proliferation of retinoblastoma cells. Meanwhile,
      the restoration of EZH2 or HDAC9 expression countered the anti-proliferative
      effect of miR-101-3p on WERI-Rb-1 and Y79 cells. Collectively, these data
      highlight the role of miR-101-3p in the tumorigenesis of retinoblastoma, and
      indicate its suitability as a novel therapeutic target.

PMID- 30186386
TI  - Role of ALK5/SMAD2/3 signaling in the regulation of NOX expression in cerebral
      ischemia/reperfusion injury.
AB  - Nicotinamide adenine dinucleotide phosphate oxidase (NOX)-derived reactive oxygen
      species (ROS) serve an important role in cerebral ischemia/reperfusion (I/R)
      injury. However, the mechanism by which ROS generation is regulated has not yet
      been fully elucidated. The present study aimed to explore the role of
      transforming growth factor-beta signaling in ROS generation. Sprague Dawley rats
      were subjected to I/R injury and PC-12 cells were transfected with small
      interfering RNA against activin receptor-like kinase (ALK)5 or
      hypoxia/reoxygenation (H/R). The results indicated that I/R or H/R significantly
      increased ALK5 expression, SMAD2/3 phosphorylation and NOX2/4 expression and
      activity, concomitant with ROS generation and apoptosis. In addition, ALK5
      knockdown significantly reversed changes induced by H/R treatment in PC-12 cells.
      These results suggest that ALK5/SMAD2/3 signaling serves a key role in oxidative
      stress. To the best of our knowledge, this is the first study to demonstrate that
      ALK5/SMAD2/3 activation is associated with the regulation of NOX2/4 expression
      and exacerbates I/R injury.

PMID- 30186387
TI  - Relationship between serum levels of miR-204 and clinical features of patients
      with lumbar disc herniation - an analysis based on 1,589 cases.
AB  - This study aims to investigate the relationship between serum miR-204 and
      clinical features of patients with lumbar disc herniation (LDH). Clinical data of
      1589 LDH patients were retrospectively analyzed. There were 953 patients (group
      A) with a duration of disease shorter than 3 months, and another 636 patients
      (group B) with a duration of disease longer than 3 months. A total of 300 healthy
      volunteers were also selected in the same period. Results showed that there was
      no significant difference in miR-204 expression between males and females
      (p>0.05). No significant differences in miR-204 expression level were found among
      different ages (p>0.05). miR-204 in patients with LHD at or below the fourth
      lumbar vertebrae was significantly higher than those in patients with LHD above
      the fourth lumbar vertebrae (p<0.05). miR-204 in 1485 patients with abnormal
      lumbar spine activity was higher than those in healthy controls (p<0.05). miR-204
      expression levels was higher in patients with low back pain than those in
      patients without low back pain. Among patients with low back pain, miR-204 level
      in patients with spasm-like waist pain was significantly higher than that in
      patients with persistent dull low back pain (p<0.05). miR-204 increased with the
      increase in degree of limited walking (p<0.05). There was no significant
      difference in miR-204 expression level between patients with bilateral lower limb
      symptoms and patients with unilateral lower limb symptoms (p>0.05), while miR-204
      was significantly higher in patients with lower limb symptoms than that in
      patients without the symptoms (p<0.05). miR-204 was correlated with knee tendon
      reflex, heel tendon reflex and degree of straight leg raise abnormality. miR-204
      was significantly decreased in patients with improvement after treatment. miR-204
      level was closely related to the clinical characteristics of LDH. miR-204 may
      potentially serve as a prognostic marker for patients with LDH.

PMID- 30186388
TI  - Estrogen relaxes gastric muscle cells via a nitric oxide- and cyclic guanosine
      monophosphate-dependent mechanism: A sex-associated differential effect.
AB  - Various gastrointestinal (GI) disorders have a higher prevalence in women than in
      men. In addition, estrogen has been demonstrated to have an inhibitory effect on
      the contractility of GI smooth muscle. Although increased plasma estrogen levels
      have been implicated in GI disorders, the role of gastric estrogen receptor (ER)
      in these sex-specific differences remains to be fully elucidated. The present
      study was designed to investigate the sex-associated differences in the
      expression of the two ER isoforms, ERalpha and ERbeta, and the effect of estrogen
      on gastric muscle contraction via the nitric oxide (NO)/cyclic guanosine
      monophosphate (cGMP) pathway. Experiments were performed on single gastric smooth
      muscle cells (GSMCs) isolated from male and female Sprague Dawley rats. The
      effect of acetylcholine (ACh), a muscarinic agonist, on the contraction of GSMCs
      was measured via scanning micrometry in the presence or absence of 1 uM 17beta
      estradiol (E2), an agonist to the majority of ERs, 1,3,5-tris(4-hydroxyphenyl)-4
      propyl-1H-pyrazole (PPT), an ERalpha agonist, or diarylpropionitrile (DPN), an
      ERbeta agonist. The protein expression levels of ER subtypes in GSMCs were
      measured using a specifically designed ELISA. GSMCs from female rats had a higher
      expression of ERalpha and ERbeta protein compared with GSMCs from males. ACh
      induced less contraction in female that in male GSMCs. Pre-treatment of GSMCs
      with E2 reduced the contraction of GSMCs from both sexes, but to a greater extent
      in those from females. PPT and DPN inhibited ACh-induced contraction in GSMCs
      from females. Furthermore, E2 increased NO and cGMP levels in GSMCs from males
      and females; however, higher levels were measured in females. Of note, pre
      incubation of female GSMCs with Nomega-nitro-L-arginine, a NO synthase inhibitor,
      or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, a guanylyl cyclase inhibitor,
      reduced the inhibitory effect of estrogen on GSMC contraction. In conclusion,
      estrogen relaxes GSMCs via an NO/cGMP-dependent mechanism, and the reduced
      contraction in GSMCs from females by estrogen may be associated with the sex
      associated increased expression of ERalpha and ERbeta, and greater production of
      NO and cGMP, compared with that in GSMCs from males.

PMID- 30186389
TI  - Decreased expression of microRNA-214 contributes to imatinib mesylate resistance
      of chronic myeloid leukemia patients by upregulating ABCB1 gene expression.
AB  - The aim of the present study was to determine the expression of adenosine
      triphosphate binding cassette subfamily B member 1 (ABCB1) gene and its protein P
      glycoprotein (PGP) in bone marrow mononuclear cells from chronic myeloid leukemia
      (CML) patients with imatinib mesylate (IM) resistance, or IM-resistant CML K562
      cells. In addition, the molecular mechanism of action of microRNA (miR)-214 on
      ABCB1 in IM resistance was investigated. A total of 26 CML patients with IM
      resistance were included in the present study. In addition, 31 CML patients who
      did not have IM resistance were included as the control group. Bone marrow was
      collected from all subjects. The K562R cell line, which is a K562 cell line with
      IM resistance, was used for cellular studies. Reverse transcription-quantitative
      polymerase chain reaction was used to determine the expression of ABCB1 mRNA and
      miR-214 in cells. Western blotting was employed to determine the expression of
      PGP. Dual luciferase reporter assay was carried out to identify interactions
      between ABCB1 mRNA and miR-214. MTT assay was used to determine the survival rate
      of cells. ABCB1 mRNA and PGP expression was upregulated in bone marrow
      mononuclear cells from CML patients with IM resistance. K562R cells had higher
      ABCB1 and PGP expression than K562 cells, potentially due to their different
      sensitivity to IM. Expression miR-214 was decreased in bone marrow mononuclear
      cells from patients with IM resistance and K562R cells. Notably, miR-214 was able
      to bind with the 3'-untranslated region, seed region of ABCB1 mRNA to regulate
      its expression. In addition, elevated expression of miR-214 restored IM
      sensitivity to K562R cells potentially by affecting ABCB1 expression. The present
      study demonstrated that upregulated expression of ABCB1 mRNA and PGP in bone
      marrow mononuclear cells from CML patients with IM resistance may be associated
      with the downregulation of miR-214. In addition, miR-214 may participate in the
      IM resistance of CML patients by regulating ABCB1 expression.

PMID- 30186390
TI  - Expression of miR-376 in blood of pregnant women with preeclampsia and its effect
      on 25-hydroxyvitamin D.
AB  - The study aims to investigate the clinical significance of regulating the
      expression of 25-hydroxyvitamin D (25-OH-VD) via microRNA (miRNA)-376c in the
      occurrence and development of preeclampsia (PE) in pregnant women. Peripheral
      blood and placental tissues were collected from pregnant women in 4 groups,
      including 67 normal pregnant women, 41 pregnant women with gestational
      hypertension, 40 pregnant women with mild PE and 51 pregnant women with severe
      PE. The expression of 25-OH-VD and miRNA-376c in peripheral blood were analyzed
      via reverse transcription-quantitative polymerase chain reaction (RT-qPCR); the
      protein expression of 25-OH-VD was analyzed via western blotting, and the
      clinical significance of its expression was also analyzed. The expression of
      miRNA-376c in peripheral blood in pregnant women was decreased (P<0.01), and the
      expression of 25-OH-VD in peripheral blood was significantly decreased (P<0.01);
      there was a significantly positive correlation between the expression of miRNA
      376c and 25-OH-VD (P<0.01). There was a significantly positive correlation
      between miRNA-376c and the protein expression of 25-OH-VD in placental tissues
      (P<0.01). The downregulation of miRNA-376c expression in peripheral blood and
      placental tissues in pregnant women had significantly positive correlations with
      gestational age, plasma albumin level and fetal weight, but had significantly
      negative correlations with blood pressure and urinary protein level. (P<0.01).
      The downregulation of 25-OH-VD expression in placental tissues also had such
      correlations. The low expression of miRNA-376c in PE patients is involved in the
      occurrence and development of PE through downregulating the expression of 25-OH
      VD.

PMID- 30186391
TI  - Identification of miRNAs associated with the mechanical response of hepatic
      stellate cells by miRNA microarray analysis.
AB  - It has been suggested that hepatic stellate cells (HSCs) could be used in the
      regulation of liver microcirculation and portal hypertension. The effects of
      tensile strain on the microRNA (miRNA) profile of HSCs are largely unknown. In
      this study, we aimed to explore the changes of miRNA expression in tensile strain
      treated HSCs. The purity and activation of HSCs were determined by
      immunofluorescence staining with antibody against desmin and a-SMA, respectively.
      miRNA profile analysis was performed on HSCs with and without tensile strain
      treatment (n=3) using microarray analysis. We identified 6 significantly
      differentially expressed miRNAs (DEMs), including 1 downregulated (rno-miR-125b-2
      3p) and 5 upregulated (rno-miR-1224, rho-miR-188-5p, rho-miR-211-3p, rho-miR-3584
      5p and rho-miR-466b-5p), which were validated by reverse transcription
      quantitative polymerase chain reaction (RT-qPCR) experiments. Further analysis of
      the DEMs revealed that many important biological processes and signal pathways
      were triggered in tensile strain-treated HSCs. These include the signal
      transduction mechanisms associated with protein binding, apoptosis,
      proliferation, and the FoxO and Wnt signaling pathways. In conclusion, this study
      presents the specific DEMs in tensile strain-treated HSCs. Our study provide
      novel miRNA-based information that may enhance our understanding of the
      pathophysiological processes leading to portal hypertension.

PMID- 30186392
TI  - Bletilla striata polysaccharide has a protective effect on intestinal epithelial
      barrier disruption in TAA-induced cirrhotic rats.
AB  - It has been reported that intestinal epithelial barrier dysfunction serves an
      important role in the development of liver cirrhosis. However, at present there
      is no satisfactory treatment for intestinal mucosal lesions and ulcers associated
      with cirrhosis. The aim of the present study was to investigate the effect of
      Bletilla striata polysaccharide (BSP) on intestinal epithelial barrier disruption
      in rats with thioacetamide (TAA)-induced liver cirrhosis. Rats were randomly
      divided into 5 groups (n=10): BSP low dosage (15 mg/kg), BSP middle dosage (30
      mg/kg), BSP high dosage (60 mg/kg), experiment and control groups. All groups
      except control group were administered with TAA (200 mg/kg/day) to induce liver
      cirrhosis. Following modeling, rats in the low, middle and high-dose BSP groups
      received BSP. ELISA kits were used to measure the endotoxin, alanine transaminase
      (ALT) and aspartate transaminase (AST) levels in the portal vein, while
      interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha expression in the ileal
      tissue was measured. Reverse transcription-quantitative polymerase chain reaction
      (RT-qPCR) and western blotting were used to detect the expression of zonula
      occludens (ZO)-1 and occludin mRNA and protein, respectively. Intestinal
      epithelial tissue pathology was detected using hematoxylin-eosin (HE) staining.
      Immunohistochemistry was performed to assess the expression of ZO-1 and occludin
      in intestinal epithelial tissues. Following treatment with BSP, ALT, AST and
      endotoxin levels in the portal vein, as well as IL-6 and TNF-alpha expression in
      ileal tissues, were significantly decreased compared with model group (P<0.05 or
      0.01). Furthermore, BSP treatment upregulated the expression of ZO-1 and occludin
      mRNA and protein compared with the model group (P<0.05 or 0.01) and cytoplasmic
      staining for these proteins was increased. The degree of intestinal epithelial
      tissue pathological damage was significantly reduced in the BSP groups. In
      conclusion, BSP is able to reduce endotoxin levels, inhibit the inflammatory
      cytokines IL-6 and TNF-alpha and elevate expression of ZO-1 and occludin at tight
      junctions. Together, these results suggest a novel protective agent for the
      restoration of intestinal epithelial barrier disruption.

PMID- 30186393
TI  - Flexible ureteroscopic holmium laser lithotripsy with PolyScope for senile
      patients with renal calculi.
AB  - The present study reported the clinical experience of using a PolyScope with
      holmium laser lithotripter in managing renal calculi in senile patients. Between
      December 2013 and December 2016, 157 senile patients (69.1+/-6.1 years old) were
      treated with PolyScope holmium laser lithotripsy for renal calculi at Xin Hua
      Hospital (Shanghai, China). The mean stone digitized surface area was 154.2+/
      57.7 mm2 (range, 55.8-478.3 mm2). A thorough medical history investigation, and
      laboratory and radiological examination were followed by proper preoperative
      management. The PolyScope was then passed into the renal cavities following the
      position of the ureteral access sheath, with laser energy maintained at 1.0-2.0
      J, frequency 10-15 Hz. The demographical and operative information of senile
      patients were compared with that of the 332 non-senile patients operated at the
      same period time. The average operative time was 54.6+/-13.2 min (range, 37-124
      min). No major complications, including ureteral perforation or sepsis were
      encountered. The single session stone-free rate (SFR) was 81.5% and the overall
      SFR was 89.2%, similar to that of the non-senile group. PolyScope combined with
      holmium laser lithotripter is safe and effective in managing renal calculi in
      senile patients compared with non-senile patients, with considerately high SFRs
      and low complication rates.

PMID- 30186394
TI  - Effects of transplanted adipose derived stem cells on the expressions of alpha
      SMA and DCN in fibroblasts of hypertrophic scar tissues in rabbit ears.
AB  - To study the effects of transplanted adipose derived stem cells (ADSCs) on the
      expressions of alpha-smooth muscle actin (alpha-SMA) and decorin (DCN) in
      fibroblasts of hypertrophic scar tissues in rabbit ears. Twelve New Zealand white
      rabbits were selected; the normal subcutaneous adipose tissues in inguinal region
      were removed, ADSCs were extracted via enzyme digestion, cultured in Dulbecco's
      modified Eagle's medium (DMEM) and inoculated into the culture dish (3-5*104
      cells/ml). After the rabbit ear hypertrophic scar model was established
      successfully, the fibroblasts of hypertrophic scar tissues in rabbit ears were
      separated and cultured using the mechanical method combined with enzyme
      digestion, and the ADSCs and scar fibroblasts were cultured in non-contact
      Transwell co-culture system for 21 days (experimental group); the corresponding
      scar fibroblasts were cultured in an ordinary 6-well plate without any treatment
      for 21 days (control group). The content of collagen I in fibroblasts was
      detected using the enzyme-linked immunosorbent assay (ELISA) kit, the mRNA
      expressions of alpha-SMA and DCN were detected via reverse transcription
      polymerase chain reaction (RT-PCR), the protein expressions of alpha-SMA and DCN
      were detected via western blot analysis, and the expressions and distribution of
      alpha-SMA and DCN were detected via immunofluorescence assay. The results of
      ELISA showed that the content of collagen I in experimental group was decreased
      significantly (p<0.01). The results of RT-PCR and western blot analysis revealed
      that the mRNA and protein expression levels of alpha-SMA were significantly
      decreased (P<0.01, but those of DCN were significantly increased (p<0.01).
      Moreover, the results of immunofluorescence assay showed that the expression of
      alpha-SMA in experimental group was significantly decreased, while the expression
      of DCN was significantly increased. ADSCs can inhibit the mRNA and protein
      expressions of alpha-SMA and promote the mRNA and protein expressions of DCN in
      in vitro culture system, and they are expected to be used in the prevention and
      treatment of pathological scars.

PMID- 30186395
TI  - Histopathological changes and onset of severe hepatic steatosis in rats fed a
      choline-free diet.
AB  - Hepatic steatosis significantly increases morbidity and mortality associated with
      major liver surgery. Several rodent models of hepatic steatosis have been
      previously reported, which aimed to investigate the effect of various
      pharmaceutical agents and interventional procedures on the pathophysiology of
      steatotic liver. The aim of the present study was to investigate the time frame
      of severe hepatic steatosis in rats after they were fed a choline-free diet and
      any associated histopathological changes. The duration of feeding with a choline
      free diet required to develop severe hepatic steatosis was investigated in Wistar
      rats. The severity of hepatic steatosis in liver specimens was evaluated at 8,
      10, 12 and 14 weeks following the onset of the choline-free diet. Comparisons
      were made with rats receiving standardized laboratory food. Feeding rats for 12
      13 weeks with a choline-free diet led to 66% fatty liver infiltration, which
      exceeded 68% after 14 weeks. Prior to 8 weeks, the fatty infiltration reached
      43%, with a gradual increase revealing a stronger rate from 8-12 weeks and a
      gradual decline after 14 weeks. At 12-13 weeks the fatty infiltration was
      considered representative of severe hepatic steatosis. Macrovesicular fatty
      infiltration revealed a significant increase at a steady rate between 8 and 14
      weeks, with evidence of the onset of lobular inflammation and steatohepatitis
      after 14 weeks of feeding with the choline-free diet. Microvesicular fatty
      infiltration demonstrated a lower growth rate between 8 and 12 weeks while
      maintaining a steady rate between 12 and 14 weeks. Mixed fatty infiltration
      maintained its steady rate of hepatic parenchyma from 8.8-9.5%. Rats fed with the
      standard laboratory diet did not demonstrate fatty infiltration >4.5%, so they
      did not develop hepatic steatosis. Developing an ideal model of hepatic steatosis
      is a particular challenge. The findings of the present study indicate that severe
      hepatic steatosis in rodents may lead to the development of steatohepatitis after
      feeding with a choline-free diet for at least 14 weeks. This model is of
      particular interest in experimental liver surgery and associated surgical
      maneuvers, and is easily reproducible.

PMID- 30186396
TI  - Effects of different doses of dexmedetomidine on analgesic efficacy and
      inflammatory cytokines in patients undergoing laparoscopic surgery.
AB  - The effects of different doses of dexmedetomidine on analgesic efficacy and
      inflammatory cytokines in patients with laparoscopic surgery were investigated. A
      total of 179 laparoscopic patients from March 2015 to May 2017 were enrolled and
      randomly divided into the control group (group A) and three experimental groups
      with different doses of dexmedetomidine (group B: 0.25; group C: 0.5 and group D:
      1 ug/kg). Results showed that there was no significant difference between the
      four groups in the operation time, the amount of surgical bleeding and
      intraoperative fluid infusion. The VAS score of group A was significantly higher
      than the other three groups. In addition, the VAS score of group D at each time
      point was the lowest. There was no significant difference regarding the agitation
      score and sedation score between group A and group B. Furthermore, the
      restlessness score and sedation score in group C were significantly lower than
      those in group A and group B. Next we found that CRP and TNF-alpha in group A and
      group B were significantly higher than those in groups C and D. In addition, IL
      10 in group D was significantly higher than that in group C. Moreover, patients
      in group C had the least adverse reaction effects. In conclusion, medium dosage
      of dexmedetomidine cannot only effectively relieve the pain of laparoscopic
      patients but also regulate the secretion of inflammatory cytokines.

PMID- 30186397
TI  - Lund exhaust on hemodynamic parameters and inflammatory mediators in patients
      undergoing cardiac valve replacement under cardiopulmonary bypass.
AB  - The effect of Lund exhaust technique on hemodynamics and inflammatory mediators
      in patients undergoing cardiac valve replacement under cardiopulmonary bypass was
      evaluated. A total of 60 patients with heart disease undergoing elective heart
      valve replacement under elective cardiopulmonary bypass were randomly divided
      into Lund exhaust group (group A) and control group (group B), with 30 patients
      in each group. Group A underwent Lund exhaust during cardiopulmonary bypass,
      while group B was identical to group A except for not using the Lund exhaust
      technique during cardiopulmonary bypass. The hemodynamic parameters at different
      time-points showed that the indexes of MAP, PASP, CO, CI, PCWP, CVP and SVR in
      T1, T2, T3 and T4 moments between group A and group B were statistically
      significant (p<0.05). There was no statistical significance in IL-6, IL-8, IL-10,
      TNF-alpha and TIMP-1 between group A and group B patients at the T0 moment
      (p>0.05). The levels of IL-6, IL-8, IL-10, TNF-alpha and TIMP-1 in group B
      patients at T1, T2, T3 and T4 moments were statistically significant compared
      with those in group A (p<0.05). The IL-6, IL-8, TNF-alpha indexes of group B
      patients were statistically significant at the T5 moment compared with those in
      group A (p<0.05). The IL-10 and TIMP-1 of two groups were not statistically
      significant at the T5 moment. The operating time, CPB time, aortic clamp time,
      intraoperative blood loss, postoperative tube time, ICU stay time, hospital stay
      time and pulmonary infection of patients in group A were significantly less than
      those in group B. In conclusion, Lund exhaust technology can significantly reduce
      the fluctuation of hemodynamics, decrease the expression of inflammatory factors,
      improve lung function, and is conducive to the rehabilitation of patients.

PMID- 30186398
TI  - Early ultrasound-guided percutaneous catheter drainage in the treatment of severe
      acute pancreatitis with acute fluid accumulation.
AB  - The clinical effect of early percutaneous ultrasound guided percutaneous catheter
      drainage (PCD) in treating severe acute pancreatitis complicated with acute fluid
      accumulation in the abdominal cavity was analyzed. A total of 178 patients with
      severe acute pancreatitis complicated with acute fluid accumulation in peritoneal
      cavity admitted from January, 2011 to January, 2015 to Chuiyangliu Hospital were
      retrospectively analyzed. Based on the treatment, patients were divided into the
      following groups: PCD group and conservative treatment control group. Time-period
      of systemic inflammatory response (SIRS), time-period of abdominal pain, bowel
      sounds recovery time, dietary recovery time, hospitalization days, white blood
      cell count, serum amylase, C-reactive protein, serum calcium and complications in
      both groups were observed and compared. The measurement data between the two
      groups were presented as mean +/- standard deviation (+/-SD), and analyzed by t
      test. Classification data were analyzed by the Chi-square test, with P<0.05
      indicating a statistically significant difference. Time-period of systemic
      inflammatory response (SIRS), time-period of abdominal pain, bowel sounds
      recovery time, dietary recovery time and hospitalization days were shorter in the
      PCD group than those in the control group (P=0.001). Improvements of white blood
      cell count, serum amylase, C-reactive protein and serum calcium were better than
      those of the control group (P<0.001), the rate of transferring to surgical
      department in the PCD group was lower than that of the control group (P=0.042),
      and complications of severe acute pancreatitis were not significantly different
      in the two groups (P>0.05). In this study, 6 adverse events occurred in the PCD
      group, accounting for 7.9% (6/76), including 1 case of puncture bleeding and 5
      cases of obstruction. In conclusion, early ultrasound-guided PCD in treating
      severe acute pancreatitis is effective and safe.

PMID- 30186399
TI  - Gambogic acid regulates the migration and invasion of colorectal cancer via
      microRNA-21-mediated activation of phosphatase and tensin homolog.
AB  - Gambogic acid (GA) has been reported to inhibit cancer cell proliferation and
      migration and enhance apoptosis. Several signaling pathways were identified to be
      involved in GA function, including PI3K/Akt, caspase-3 apoptosis and TNF-alpha/NF
      kappaB. However, to the best of our knowledge, the association between miRNA and
      GA has not been explored. The present study initially demonstrated that GA could
      inhibit HT-29 cancer cell proliferation using an MTT assay. In addition, a
      Transwell assay and a wound-healing assay respectively indicated that GA
      inhibited HT-29 cancer cell invasion and migration, which was also confirmed by
      the increased MMP-9 protein expression. Furthermore, GA induced the apoptosis of
      HT-29 cancer cells in an Annexin V and PI double staining assay. Moreover,
      treatment with GA significantly decreased miR-21 expression in these cells.
      Additionally, western blot analysis demonstrated that GA treatment enhanced the
      activation of phosphatase and tensin homolog (PTEN) along with the suppression of
      PI3K and p-Akt. Furthermore, miR-21 mimics reversed all the aforementioned
      activities of GA, which indicated that miR-21 was the effector of GA and blocked
      PI3K/Akt signaling pathway via enhancing PTEN activity. In summary, GA induced HT
      29 cancer cell apoptosis via decreasing miR-21 expression and blocking PI3K/Akt,
      which may be a useful novel insight for future CRC treatment.

PMID- 30186400
TI  - Serum anion gap on admission predicts intensive care unit mortality in patients
      with aortic aneurysm.
AB  - It has been widely reported that the serum anion gap is significantly associated
      with mortality in intensive care unit (ICU); however, it remains unknown whether
      the association is present in aortic aneurysm (AA) patients. The present study
      aimed to investigate the association between the admission serum anion gap and
      ICU mortality in AA patients. Data extracted from a publicly accessible clinical
      database using a modifiable data mining technique were analyzed retrospectively,
      mainly by employing multivariable logistic regression analysis. The primary study
      outcome was ICU mortality. A total of 273 patient records were analyzed. The ICU
      mortality was 8.79% (24/273). The median serum anion gap was significantly higher
      in non-survivors [17.50 mEq/l, interquartile range (IQR) 15.75-22.50 mEq/l]
      compared with survivors [13.00 mEq/l, IQR 11.00-15.00 mEq/l, P<0.001].
      Multivariate analysis resulted in identification of a clear association between
      admission serum anion gap and ICU mortality in AA patients [odds ratio (OR) 1.38
      per 1 mEq/l increase, 95% confidence interval (CI) 1.08-1.76]. The area under the
      receiver operating characteristic curve showed an outstanding discrimination
      ability in predicting ICU mortality (area under curve 0.8513, 95% CI 0.7698
      0.9328). In conclusion, admission serum anion gap may serve as a strong predictor
      of ICU mortality for AA patients.

PMID- 30186401
TI  - Effects of dexmedetomidine hydrochloride on hemodynamics, postoperative analgesia
      and cognition in cesarean section.
AB  - The present study aims to investigate the effects of dexmedetomidine
      hydrochloride (Dex) on hemodynamics, postoperative analgesia and cognition in
      cesarean section. One hundred and two pregnant women who underwent cesarean
      section were selected from August 2016 to July 2017 in People's Hospital of
      Zhangqiu District and randomly divided into control group and observation group.
      Control group was anesthetized with bupivacaine hydrochloride, and morphine +
      ropivacaine hydrochloride were given postoperatively. Observation group received
      intraoperative anesthesia with bupivacaine hydrochloride and Dex, and Dex +
      ropivacaine hydrochloride were given for postoperative analgesia. Hemodynamic
      factors were compared between the two groups. Postoperative Ramsay sedation
      score, the incidence of adverse reactions and the incidence of transient
      neurological syndrome (TNS) were compared between the two groups. Montreal
      Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE) scoring were
      performed to evaluate the cognitive function of the two groups. The mean arterial
      pressure (MAP) and visual analogue scale (VAS) scores of the observation group
      after anesthesia were significantly lower than those of control group (P<0.05).
      The Ramsay sedation score of the observation group was significantly better than
      that of control group at different time-points after surgery (P<0.05). Incidence
      of postoperative agitation in observation group was significantly lower than that
      in control group (P<0.05). Incidence of TNS in observation group was
      significantly lower than that in control group during 1 week after surgery
      (P<0.05). MoCA and MMSE scores of the observation group were better than that of
      control group at 1 day after operation (P<0.05). The use of Dex anesthesia in
      cesarean section can achieve more stable hemodynamic conditions during
      perioperative period and more obvious analgesic effect after operation. It also
      reduced the incidence of postoperative TNS and cognitive dysfunction, and had
      important clinical significance.

PMID- 30186402
TI  - Therapeutic effect of MIPPSO in the thoracolumbar vertebra fracture.
AB  - The purpose of this study was to compare the efficacy of minimally invasive
      percutaneous pedicle screw osteosynthesis (MIPPSO) and traditional open pedicle
      screw osteosynthesis (TOPSO) in the treatment of thoracolumbar vertebra fracture.
      A retrospective case-control study was conducted in 120 patients with
      thoracolumbar vertebral fractures treated in the Affiliated Jiangyin Hospital of
      Southeast University Medical School (Jiangyin, China) from January 2013 to
      September 2014. They were randomly divided into two groups: MIPPSO and TOPSO
      groups with 60 cases in each group. The operation time, blood loss, incision
      length, post-operative bed rest time, hospital stay, visual analogue scale (VAS)
      pain scores and Oswestry disability index (ODI) scores before and after operation
      were recorded and analyzed. Inflammatory indexes including serum C-reactive
      protein (CRP) and creatine kinase (CK), the anterior vertebral height ratio and
      kyphosis Cobb's angle changes were also observed. The basic data of the two
      groups were similar, and there was no significant difference in the operation
      time between the two groups. The perioperative blood loss, length of incision,
      bed rest time and total hospital stay in the minimally invasive group were less
      than those in the open group. Levels of post-operative inflammation indicators
      such as CRP and CK were significantly higher than those of pre-operative
      (P<0.05), which was more obvious in the TOPSO group (P<0.05). VAS, ODI scores,
      anterior vertebral height and Cobb's angle were significantly improved at three
      days, one and 12 months after surgery compared with those before operation.
      MIPPSO for the treatment of thoracolumbar fractures can achieve similar clinical
      effects with traditional incision surgery. In addition, it has the advantages of
      less trauma, less bleeding and shorter post-operative bed rest time and hospital
      stay.

PMID- 30186403
TI  - A meta-analysis on anterior cruciate ligament reconstruction: Is modified
      transtibial technique inferior to independent drilling techniques?
AB  - This report respectively compared the standard transtibial (sTT) technique to the
      independent drilling (ID) techniques applied to anterior cruciate ligament (ACL)
      reconstruction. It also made a comparison between the clinical results of the
      modified transtibial (mTT) technique and of the ID techniques. Prospective
      studies on transtibial (TT) and ID techniques for ACL reconstruction were
      retrieved from several databases and a subgroup analysis was performed to compare
      the sTT technique with the ID techniques and the mTT with the ID techniques.
      Furthermore, comparison of the Lachman test, pivot-shift test, International Knee
      Documentation Committee (IKDC) subjective and objective evaluations, Lysholm
      score and Tegner activity scale were conducted. This report included 12 clinical
      studies that involved 681 patients having received ACL reconstruction. The study
      results indicated that in comparison between the sTT and ID techniques, the ID
      techniques outperformed the sTT technique in the IKDC subjective score (P=0.01)
      and laxity (P=0.0004). However, there was no significant difference in the IKDC
      objective score (P=0.34), pivot-shift test (P=0.24), Lachman test (P=0.21),
      Lysholm score (P=0.14) and Tegner activity scale (P=0.66). The comparison between
      the new mTT technique and the ID techniques suggested no significant difference
      in the IKDC objective and subjective scores (P=0.86), laxity (P=0.38), pivot
      shift test (P=0.66), Lachman test (P=0.10), Lysholm score (P=0.10) and Tegner
      activity scale (P=0.55). Compared to the sTT technique, the mTT and ID techniques
      are more suitable for ACL reconstruction because they can present better
      subjective feelings. Moreover, considering that the TT technique is familiar to
      surgeons and the mTT technique can bring favorable subjective feelings and
      objective clinical outcomes, the mTT technique shows greater utilization
      potential.

PMID- 30186404
TI  - Pirfenidone suppresses bleomycin-induced pulmonary fibrosis and periostin
      expression in rats.
AB  - The aim of the present study was to investigate the effect of pirfenidone on
      bleomycin-induced lung fibrosis in rats, in order to elucidate the underlying
      mechanism of periostin-induced fibrosis. The lung fibrosis model was constructed
      using a single intratracheal instillation of bleomycin in rats. The normal rats
      without bleomycin administration were used as controls (n=24). Bleomycin-treated
      rats were randomized into the model (M) or pirfenidone (P) group (n=24 per
      group). Rats were sacrificed on days 7, 14 and 28 following treatment.
      Hematoxylin-eosin and Masson's trichrome staining were performed to analyze
      pulmonary alveolitis and fibrosis. Periostin location was detected by
      immunohistochemistry. Hydroxyproline content, and expression of periostin and
      transforming growth factor (TGF)-beta1 were detected by ELISA, reverse
      transcription-quantitative polymerase chain reaction or western blotting.
      Correlation of periostin expression with hydroxyproline and TGF-beta1 content was
      also analyzed. Histological findings demonstrated that pirfenidone significantly
      inhibited bleomycin-induced lung fibrosis and reduced the hydroxyproline content
      on day 14 and day 28 compared with the model group (P<0.05 or P<0.01).
      Furthermore, the bleomycin-induced increased protein expression of periostin and
      TGF-beta1 was also significantly suppressed by pirfenidone on days 14 (P<0.01)
      and 28 (data not shown). Furthermore, periostin expression was significantly
      correlated with hydroxyproline and TGF-beta1 content, and fibrosis score
      (P<0.001). The present findings suggest that the antifibrotic effect of
      pirfenidone may be achieved by suppression of periostin and TGF-beta1 expression
      in rat pulmonary fibrogenesis.

PMID- 30186405
TI  - Dynamic expression of matrix metalloproteinases 2, 9 and 13 in ovariectomy
      induced osteoporosis rats.
AB  - The aim of the present study was to examine the dynamic expression of matrix
      metalloproteinase (MMP)-2, MMP-9 and MMP-13 in an ovariectomy (OVX)-induced
      osteoporosis rat model. A total of 80 Sprague-Dawley female rats (age, 3 months)
      were randomly divided into the OVX and sham groups, with 40 rats in each group.
      Rats in the sham group received sham surgery, while the remaining rats were
      ovariectomized. After 12, 16, 20 and 24 weeks, 10 rats from each group were
      randomly sacrificed, respectively. It was observed that the bone mineral density
      (BMD) and the trabecular bone area in the OVX group were significantly lower as
      compared with those in the sham group (P<0.01). The expression levels of MMP-2
      and MMP-9 were negatively correlated with the BMD, while MMP-13 was positively
      correlated with the BMD. The expression levels of MMP-2 and MMP-9 increased more
      abruptly and were significant higher in the OVX group in comparison with those in
      the sham group between 12 and 24 weeks after surgery (P<0.01). More specifically,
      the MMP-9 mRNA expression level in the OVX group increased abruptly between 12
      and 24 weeks after surgery. By contrast, in the sham group, the MMP-9 mRNA level
      was undetectable between 12 and 16 weeks, and increased steadily between 16 and
      24 weeks. Furthermore, the mRNA and protein expression levels of MMP-13 initially
      increased and then decreased in the OVX group (P<0.01 vs. the sham group),
      whereas they continuously increased in the sham group between 12 and 24 weeks
      after surgery. In conclusion, MMP-2, MMP-9 and MMP-13 regulated the development
      of osteoporosis, and MMP-9 may be used as an important marker in the early
      diagnosis of osteoporosis.

PMID- 30186407
TI  - Fmr1 protects cardiomyocytes against lipopolysaccharide-induced myocardial
      injury.
AB  - The present study explored the mechanisms by which fragile X mental retardation 1
      (fmr1) overexpression inhibits lipopolysaccharide (LPS)-induced cardiomyocyte
      injury. Factors including oxidative stress reaction, mitochondrial membrane
      potential variation and cell apoptosis were evaluated. The viability of H9c2
      cells was evaluated with a Cell Counting Kit-8 assay after cells were treated
      with LPS at different concentrations (0, 1, 3, 6 and 9 ug/ml) for various
      durations (4, 12 and 24 h). Flow cytometry was used to determine variations in
      reactive oxygen species (ROS), mitochondrial membrane potential and cell
      apoptosis. Reverse transcription-quantitative polymerase chain reaction and
      western blot analysis were performed to detect the levels of apoptosis-associated
      factors, and western blot analysis was used to determine the phosphorylation
      levels of phosphoinositide-3 kinase (PI3K), Akt and forkhead box (Fox)O3a. The
      results indicated that LPS decreased the viability of H9c2 cells in a dose- and
      time-dependent manner. Overexpression of fmr1 inhibited the LPS-induced decrease
      in the mitochondrial membrane potential and the production of ROS as well as
      apoptosis in H9c2 cells. Fmr1 also inhibited LPS-induced reductions in
      antioxidant enzyme activities, including those of superoxide dismutase and
      reduced/oxidized glutathione ratio, and decreased LPS-associated increases in the
      lipid peroxidation product malondialdehyde. Apoptosis-associated factors were
      identified to be involved in the effects of Fmr1. Overexpression of Fmr1
      attenuated LPS-associated increases in the apoptosis-activating factors B-cell
      lymphoma 2 (Bcl-2)-associated X protein and caspase-3 and decreases in apoptosis
      inhibitors, including Bcl-2 and X-linked inhibitor of apoptosis protein. Fmr1
      overexpression also reduced LPS-induced increases in the phosphorylation levels
      of PI3K, Akt and FoxO3a. In conclusion, fmr1 overexpression alleviated oxidative
      stress and apoptosis in H9c2 cardiomyocytes injured by LPS via regulating
      oxidative stress and apoptosis-associated factors, as well as the PI3K/Akt
      pathway. This information may provide a novel and effective therapeutic strategy
      for heart diseases.

PMID- 30186406
TI  - Downregulation of microRNA-1 attenuates glucose-induced apoptosis by regulating
      the liver X receptor alpha in cardiomyocytes.
AB  - Diabetic cardiomyopathy (DCM) is characterized by abnormal myocardial structure
      or performance. It has been suggested that microRNA-1 (miR-1) may be abnormally
      expressed in the hearts of patients with diabetes. In the present study, the role
      of miR-1 in glucose-induced apoptosis and its underlying mechanism of action was
      investigated in rat cardiomyocyte H9C2 cells. Cells were transfected with anti
      miR-1 or miR-1-overexpression plasmids and the expression of miR-1 and liver X
      receptor alpha (LXRalpha) were determined by reverse transcription-quantitative
      polymerase chain reaction analysis. The proportion of apoptotic cells was
      determined using an Annexin-V-FITC apoptosis detection kit and the mitochondrial
      membrane potential (DeltaPsi) was measured following staining with rhodamine 123.
      In addition, the expression of apoptosis-associated proteins was measured by
      western blot analysis. The results demonstrated that expression of miR-1 was
      significantly increased, whereas the expression of LXRalpha was significantly
      decreased in H9C2 cells following treatment with glucose. miR-1 knockdown
      significantly inhibited apoptosis, increased the DeltaPsi and suppressed the
      cleavage of poly (adenosine diphosphate-ribose) polymerase, caspase-3 and caspase
      9. It also significantly downregulated the expression of Bcl-2 and upregulated
      the expression of Bax. In addition, it was demonstrated that miR-1 regulates
      LXRalpha; transfection with anti-miR-1 significantly increased the expression of
      LXRalpha. Furthermore, treatment of cells with the LXR agonist GW3965 inhibited
      apoptosis in glucose-induced anti-miR-1 cells. These results suggest a novel
      function of miR-1: The regulation of cardiomyocyte apoptosis via LXRalpha, and
      provide novel insights into regarding the complex mechanisms involved in DCM.

PMID- 30186408
TI  - Lycium barbarum polysaccharides attenuates the apoptosis of hippocampal neurons
      induced by sevoflurane.
AB  - Following the application of inhalational anesthetics, including sevoflurane,
      patients may suffer from neural injury. The present study was conducted to
      explore the mechanism involved in Lycium barbarum polysaccharides (LBP) treatment
      of sevoflurane injured hippocampal neurons. Primary hippocampal neurons were
      isolated from Sprague Dawley embryonic rats. The Cell Counting Kit-8 (CCK-8)
      assay was used to detect cell viability. Furthermore, flow cytometry (FCM) was
      used to determine cell proliferation and apoptosis rates. Reverse transcription
      quantitative polymerase chain reaction (RT-qPCR) and western blot analysis were
      applied to detect the expression levels of apoptosis-related factors, including
      activated-Caspase-3, B-cell lymphoma/leukemia-2 (Bcl-2) and Bcl-2 associated X
      (Bax), phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2) and
      total ERK1/2. The results showed that LBP promoted cell viability and cell
      proliferation but inhibited cell apoptosis in neurons injured with 3%
      sevoflurane, in dose-dependent manners (100, 200 and 400 ug/ml). LBP increased
      the expression levels of Bcl-2 and p-ERK1/2, and decreased levels of activated
      Caspase-3 and Bax in a dose-dependent manner in hippocampal neurons that were
      injured with sevoflurane. In addition, ERK1/2 inhibitor reversed the above
      phenomenon in 400 ug/ml LBP and 3% sevoflurane-treated hippocampal neurons.
      Therefore, the present study indicated that LBP protected hippocampal neurons
      from sevoflurane injury, including aberrant cell apoptosis, via the ERK1/2
      pathway.

PMID- 30186409
TI  - Integrated analysis of key mRNAs and lncRNAs in osteoarthritis.
AB  - Osteoarthritis (OA) is the most common type of arthritis, observed mainly in the
      population aged >65 years. However, the mechanism underlying the development and
      progression of OA has remained largely elusive. The present study aimed to
      identify differentially expressed mRNAs and lncRNAs in OA. By analyzing the
      GSE48556 and GSE82107 datasets, a total of 202 up- and 434 downregulated mRNAs
      were identified in OA. Gene ontology and Kyoto Encyclopedia of Genes and Genomes
      pathway analysis indicated that differently expressed genes were mainly involved
      in regulating antigen processing and presentation, interspecies interaction
      between organisms, immune response, transcription and signal transduction. In
      addition, a series of long non-coding (lnc)RNAs were differently expressed in OA.
      To provide novel data on the molecular mechanisms and functional roles of these
      lncRNAs in OA, a co-expression analysis was performed, which revealed that the
      dysregulated lncRNAs were associated with transcription, signal transduction,
      immune response and cell adhesion. In addition, certain key genes in protein
      protein interaction networks were identified. The present study provided useful
      information for exploring potential candidate biomarkers for the diagnosis and
      prognosis of OA, as well as novel drug targets.

PMID- 30186411
TI  - Efficacy and safety of febuxostat for treating hyperuricemia in patients with
      chronic kidney disease and in renal transplant recipients: A systematic review
      and meta-analysis.
AB  - Febuxostat is potent and well-tolerated in the management of chronic gout.
      However, its clinical efficacy and safety in the treatment of hyperuricemia in
      patients with chronic kidney disease (CKD) and in renal transplant recipients
      have remained to be fully determined. The MEDLINE, EMBASE and Cochrane Library
      databases were searched for relevant articles. Data were extracted and pooled
      results were estimated from the standard mean difference (SMD) with 95%
      confidence intervals (95% CIs). The quality of the studies included was assessed,
      and their publication bias was examined. Four prospective randomized controlled
      trials and two retrospective observational studies were included in the
      systematic review and meta-analysis. Febuxostat administration significantly
      reduced the serum uric acid concentration in patients with CKD and in renal
      transplant recipients when compared with allopurinol or placebo in the short-term
      (1 month: SMD, -2.24; 95% CI, -3.59 to -0.89; P-value of SMD=0.001; I2, 92.4%; 3
      months: SMD, -1.20; 95% CI, -2.04 to -0.36; P-value of SMD=0.005; I2, 88.9%; 6
      months: SMD, -1.49; 95% CI, -2.68 to -0.30; P-value of SMD=0.014; I2, 92.9%).
      Furthermore, the increase in the estimated glomerular filtration rate in the
      febuxostat group was significantly higher than that in the control group (SMD,
      0.30; 95% CI, 0.031 to 0.58; P-value of SMD=0.029; I2, 0.0%). No significant
      difference in the changes in serum creatinine (Scr), low-density lipoprotein
      (LDL) and high-density lipoprotein (HDL) was identified between the two groups
      (Scr: SMD, -0.17; 95% CI, -0.97 to 0.63; P-value of SMD=0.67; I2, 79.2%; LDL:
      SMD, -0.21; 95% CI, -0.49 to 0.07; P-value of SMD=0.13; I2, 34.1%; HDL: SMD, 
      0.05; 95% CI, -0.70 to 0.61; P-value of SMD=0.89; I2, 69.2%). In conclusion,
      febuxostat is a potent and well-tolerated agent for the short-term management of
      hyperuricemia in patients with CKD and in renal transplant recipients. However,
      these data should be interpreted with caution due to the varied design of the
      studies included in the present meta-analysis.

PMID- 30186410
TI  - Identification of key pathways and biomarkers in sorafenib-resistant
      hepatocellular carcinoma using bioinformatics analysis.
AB  - Hepatocellular carcinoma (HCC) is one of the most common malignant types of
      cancer, with a high mortality rate. Sorafenib is the sole approved oral clinical
      therapy against advanced HCC. However, individual patients exhibit varying
      responses to sorafenib and the development of sorafenib resistance has been a new
      challenge for its clinical efficacy. The current study identified gene biomarkers
      and key pathways in sorafenib-resistant HCC using bioinformatics analysis. Gene
      dataset GSE73571 was obtained from the Gene Expression Omnibus (GEO) database,
      including four sorafenib-acquired resistant and three sorafenib-sensitive HCC
      phenotypes. Differentially expressed genes (DEGs) were identified using the web
      tool GEO2R. Functional and pathway enrichment of DEGs were analyzed using the
      Database for Annotation, Visualization and Integrated Discovery and the protein
      protein interaction (PPI) network was constructed using the Search Tool for the
      Retrieval of Interacting Genes/Proteins and Cytoscape. A total of 1,319 DEGs were
      selected, which included 593 upregulated and 726 downregulated genes. Functional
      and pathway enrichment analysis revealed DEGs enriched in negative regulation of
      endopeptidase activity, cholesterol homeostasis, DNA replication and repair,
      coagulation cascades, insulin resistance, RNA transport, cell cycle and others.
      Eight hub genes, including kininogen 1, vascular cell adhesion molecule 1,
      apolipoprotein C3, alpha 2-HS glycoprotein, erb-b2 receptor tyrosine kinase 2,
      secreted protein acidic and cysteine rich, vitronectin and vimentin were
      identified from the PPI network. In conclusion, the present study identified DEGs
      and key genes in sorafenib-resistant HCC, which further the knowledge of
      potential mechanisms in the development of sorafenib resistance and may provide
      potential targets for early diagnosis and new treatments for sorafenib-resistant
      HCC.

PMID- 30186412
TI  - Triiodothyronine alleviates alcoholic liver disease injury through the negative
      regulation of the NLRP3 signaling pathway.
AB  - The aim of the present study was to investigate the effect and mechanism of
      triiodothyronine (T3) on alcoholic liver disease (ALD)-induced injuries in mice.
      A total of 40 male C57/BL6 mice were randomly divided into the Control, ALD,
      ALD+T3 and ALD+T3+AMP-activated protein kinase inhibitor (CC) groups. Mice were
      administered alcohol (4 g/kg/day) intragastrically for 4 weeks except for Control
      group. Mice in the ALD+T3 group were given T3 (0.1 mg/kg/day) while mice in
      ALD+T3+CC group were given T3 (0.1 mg/kg/day) and CC (10 mg/kg/day) for 1 week.
      Control and ALD groups were treated with saline. Liver tissue and blood samples
      were obtained for testing. Alanine aminotransferase (ALT), aspartate
      aminotransferase (AST) and total bilirubin (TBIL) levels were determined and
      morphological changes in the liver tissues were observed under the optical
      microscope. Inflammatory factors, including IL-1beta and transforming growth
      factor (TGF)-beta/1, alpha-smooth muscle actin (SMA) and protein levels of
      nucleotide-binding oligomerization domain, leucine rich repeat containing family,
      pyrin domain containing 3 (NLRP3), caspase-1 and pro-IL-1beta were measured.
      Serum ALT, AST and TBIL levels in the ALD+T3 group were significantly reduced
      compared with the ALD group, while they were significantly increased in the
      ALD+T3+CC group (P<0.05). The number of hepatic lobules in the ALD+T3 group was
      significantly reduced compared with the ALD group, whereas the number in the
      ALD+T3+CC group was significantly increased (P<0.05). IL-1beta and TGF-beta1
      levels in the ALD+T3 group were significantly decreased compared with the ALD
      group; however, levels in the ALD+T3+CC group were significantly increased
      compared with the ALD+T3 group (P<0.05). In addition, it was revealed that the
      expression of alpha-SMA mRNA and protein in the ALD+T3 group was significantly
      decreased compared with the ALD group, whereas it was significantly increased in
      the ALD+T3+CC group compared with the ALD+T3 group. Expression of NLRP3, caspase
      1, IL-1beta and TGF-beta1 in the ALD+T3 group was significantly decreased
      compared with the ALD group, while expression was significantly increased in the
      ALD+T3+CC group. Conversely, compared with the ALD group, expression of pro-IL
      1beta was significantly increased in the ALD+T3 group and decreased in the
      ALD+T3+CC group. In conclusion, T3 may reduce the inflammatory response and
      severity of liver cirrhosis in mice with ALD by negatively regulating the NLRP3
      signaling pathway.

PMID- 30186413
TI  - A combined study of 18F-FDG PET-CT and fMRI for assessing resting cerebral
      function in patients with major depressive disorder.
AB  - The present study investigated changes in the regional cerebral metabolic rates
      of glucose uptake (rCMRglc) using 18F-fluorodeoxyglucose (18F-FDG) positron
      emission tomography (PET) and regional homogeneity (ReHo), together with resting
      state blood oxygen level-dependent (BOLD) functional magnetic resonance imaging
      (fMRI), in patients with major depressive disorder (MDD). In total, 18 patients
      with untreated MDD and 17 healthy control subjects underwent 18F-FDG PET and BOLD
      fMRI scanning. The MDD patients' cerebral changes, measured as rCMRglc and ReHo
      values, were mapped and statistically analyzed. Compared with the control group,
      the patients with MDD had a decreased rCMRglc in the bilateral superior, middle
      and inferior frontal gyrus, in the bilateral superior and middle temporal gyrus,
      in the bilateral anterior cingulate cortex, in the bilateral putamen and caudate,
      and in the left pallidum, but an increased rCMRglc in the bilateral hippocampus
      and left thalamus. The ReHo values in the patient group were decreased in the
      bilateral superior and middle frontal gyrus, left pallidum, bilateral putamen and
      left anterior cingulate cortex, but increased in the right hippocampus and
      thalamus. No statistically significant differences were identified between
      decreased metabolism and ReHo brain regions of MDD patients (chi2=9.16; P=0.90)
      and between increased metabolism and ReHo brain regions (chi2=3.96; P=0.27), when
      comparing activated brain regions of PET and MRI. The standardized uptake values
      (SUV) of the bilateral superior, middle and inferior frontal gyrus, bilateral
      superior and middle temporal gyrus, bilateral putamen, the left caudate and
      pallidum, the left anterior cingulate cortex, and the bilateral hippocampus and
      thalamus were correlated with the ReHo (r=0.51-0.83; P<0.05). However, no
      correlation was detected between the SUV and ReHo in the right caudate and
      anterior cingulate cortex (r=0.41 and 0.37, respectively; P>0.05). Taken
      together, these results demonstrated that patients with MDD displayed
      characteristic patterns regarding changes of brain glucose uptake and ReHo in the
      resting state. Furthermore, 18F-FDG PET may be a more sensitive technique
      compared with BOLD-fMRI for the identification of brain lesions in patients with
      MDD.

PMID- 30186414
TI  - Efficacy and safety of mycophenolate mofetil for IgA nephropathy: An updated meta
      analysis of randomized controlled trials.
AB  - The efficacy and safety of mycophenolate mofetil (MMF) for immunoglobulin A
      nephropathy (IgAN) remains debatable. Therefore, the present meta-analysis was
      conducted with randomized controlled trials (RCTs). PubMed/MEDLINE, EMBASE and
      the Cochrane Central Register of Controlled Trials were analyzed to identify
      eligible trials. The pooled risk ratio (RR) with 95% confidence interval (CI) was
      estimated for all the dichotomous outcome measures. A total of eight RCTs with
      nine publications (n=510 patients) were included. No significant difference was
      noted between therapeutic regimens with and without MMF for renal remission and
      end stage renal disease (ESRD) of patients with IgAN (seven trials; RR, 1.250;
      95% CI, 0.993-1.574; P=0.057; and four trials; RR, 0.728; 95% CI, 0.164-3.236;
      P=0.676). To further define the effects of MMF for renal remission, subgroup
      analysis was performed, demonstrating that MMF was significantly more effective
      compared with the placebo (three trials; RR, 2.152; 95% CI, 1.198-3.867;
      P=0.010), although the immunosuppressive regimens with MMF had no significantly
      different effects compared with those without MMF (four trials; RR, 1.140; 95%
      CI, 0.955-1.361; P=0.146), indicating that MMF was superior to placebo and had a
      similar efficacy to other immunosuppressants for renal remission. In addition,
      subgroup analysis for ESRD revealed no significant differences between MMF and
      placebo and between the immunosuppressive regimens with and without MMF (three
      trials; RR, 0.957; 95% CI, 0.160-5.726; P=0.962; and one trial; RR, 0.205; 95%
      CI, 0.010-4.200; P=0.303). Furthermore, there were no significant differences
      between the therapeutic regimens with and without MMF in terms of the risk of
      adverse events. The present meta-analysis demonstrated that MMF was more
      effective compared with the placebo, may have similar efficacy to other
      immunosuppressants in terms of inducing renal remission of IgAN and may not
      increase the risk of adverse events. The long-term effects of MMF on the
      prognosis of patients with IgAN require verification in further studies.

PMID- 30186415
TI  - Effect of silencing lncRNATUG1 on rapamycin-induced inhibition of endothelial
      cell proliferation and migration.
AB  - Angiogenesis refers to the formation of new blood vessels from existing blood
      vessels. The proliferation and migration of endothelial cells serves a key
      function in this process. Previous research has demonstrated that rapamycin
      suppresses endothelial cell proliferation and migration, as well as angiogenesis.
      However, the mechanism by which rapamycin inhibits the proliferation and
      migration of endothelial cells remains unclear. Long noncoding RNAs (lncRNAs)
      serve a key function in the regulation of endothelial cell function. The aim of
      the current study was to investigate whether lncRNA taurine upregulated 1
      (lncRNATUG1) is involved in rapamycin-induced inhibition of proliferation and
      migration in human umbilical vein endothelial cells (HUVECs). Reverse
      transcription quantitative polymerase chain reaction results indicated that the
      expression of lncRNATUG1 was upregulated in HUVECs that had been cultured with
      rapamycin. Subsequently, HUVECs were transfected with siRNAs and CCK-8 assays
      were performed to detect cell proliferation; additionally, flow cytometry was
      employed to detect cell apoptosis, and wound healing assays were performed to
      investigate cell migration. The results demonstrated that rapamycin suppressed
      the proliferation and migration of HUVECs, and promoted the apoptosis of HUVECs.
      In addition, rapamycin downregulated the expression of vascular endothelial
      growth factor (VEGF), matrix metalloproteinase (MMP)-2 and MMP-9 in HUVECs.
      However, silencing of lncRNATUG1 was revealed to attenuate rapamycin-induced
      inhibition of cellular proliferation and migration of HUVECs, as well as
      upregulating the expression of VEGF, MMP2 and MMP-9. These results suggested that
      lncRNATUG1 regulates rapamycin-induced inhibition of endothelial cell
      proliferation and migration. Therefore, lncRNATUG1 may serve a key function in
      rapamycin-induced inhibition of endothelial cell proliferation and migration.

PMID- 30186416
TI  - Association between GDF5 single nucleotide polymorphism rs143383 and lumbar disc
      degeneration.
AB  - The association between growth differentiation factor 5 (GDF5), single nucleotide
      polymorphism (SNP) rs143383 and lumbar disc degeneration (LDD) was investigated.
      A total of 210 patients with LDD (observation group) and 320 patients without
      lumbar diseases (control group) diagnosed in Shanghai General Hospital of Nanjing
      Medical University from August 2013 to March 2017 were randomly selected. Then,
      deoxyribonucleic acid (DNA) was extracted from the blood of each patient, and Taq
      man fluorescent quantitative polymerase chain reaction (qPCR) technique was used
      to detect rs143383 in GFD5 gene. The frequency of different genotypes in
      observation group and control group was counted, and the associations between
      different SNP genotypes and the incidence of LDD were analyzed. Good genotyping
      results were found in both LDD patient group and control group. There were no
      significant differences in distribution frequency of TT and TC genotypes at site
      rs143383 between LDD patient group and control group (P>0.05), but the
      distribution frequency of CC genotype at site rs143383 in LDD patient group had a
      statistically significant difference from that in control group (P<0.05). In
      dominant models, odds ratio (OR) of (TC+CC/TT) was 1.195 (P=0.532). In recessive
      models, OR of (CC/TT+TC) was 4.333 (P=0.028). In co-dominant models, ORs of
      (TC/TT) and (CC/TT) were 0.967 and 4.43, respectively (P=0.99). The differences
      in 3 genotypes showed no statistical significance among different pathological
      grades (Grade I to V) (chi2=1.034, P=0.998), and there was no statistically
      significant difference in T and C (chi2=0.012, P=0.999). Pathological grades in
      dominant models, recessive models and over dominant models were analyzed, and no
      statistically significant difference was found (P>0.05). In conclusion, CC mutant
      type at rs143383 in GDF5 gene has a strong association with the incidence of LDD,
      and a high prevalence risk, but it has no evident correlation with pathological
      grades.

PMID- 30186417
TI  - Association of miR-182 expression in amniotic fluid with intrauterine infection
      and brain injury in premature infants.
AB  - Changes of micro-ribonucleic acid-182 (miR-182) level in cases of intrauterine
      infection were investigated to explore the association between miR-182 level
      change and brain injury in premature infants. A total of 257 preterm infants born
      in obstetrics department of Jinan Maternity and Child Care Hospital from February
      2015 to February 2017 were enrolled in this study. These preterm infants were
      divided into infected group (n=113) and uninfected group (n=144) based on
      pathological diagnosis results. Quantitative polymerase chain reaction (qPCR) was
      employed to detect miR-182 level in amniotic fluid. Bregmatic sagittal and
      coronal plus lateral fontanel craniocerebral ultrasound, craniocerebral computed
      tomography (CT) and craniocerebral magnetic resonance imaging examinations were
      conducted in these preterm infants within one week after birth, and the results
      were recorded. The relationship between intrauterine infection and brain injury
      in premature infants was analyzed, and the association of miR-182 level with
      brain injury was explored. According to pathological diagnoses, brain injury was
      found in 61 of 113 infants in the infected group, with an incidence rate of
      54.0%; and 28 of 144 infants in uninfected group, with an incidence rate of
      19.4%; among them, 3 had placental infection caused by intrauterine infection in
      pregnant women, and all preterm infants had brain damage. Risk value of brain
      injury in premature infants due to intrauterine infection was hazard ratio (HR) =
      2.2611, chi2=33.798, P<0.02. Infected group had a higher miR-182 level in
      comparison with uninfected group, and the difference in miR-182 level between
      infected group and uninfected group was statistically significant (P<0.05).
      Intrauterine infection can lead to an increase in miR-182 level; growth in miR
      182 level is closely related to brain injury in premature infants.

PMID- 30186418
TI  - Preserving hepatic artery flow during portal triad blood occlusion improves
      regeneration of the remnant liver in rats with obstructive jaundice following
      partial hepatectomy.
AB  - In certain cases, major hepatectomy is essential and inevitable in patients with
      hilar cholangiocarcinoma and obstructive jaundice (OJ). The current study was
      designed to evaluate effects of a novel method of portal blood occlusion, where
      the portal vein was occluded (OPV) and the hepatic artery flow was preserved in
      rats with OJ that underwent partial hepatectomy. OJ was induced in rats by
      ligation of the common bile duct for 7 days. Subsequently, OJ rats underwent
      hepatectomy removing 76% of the liver following occlusion of the portal triad
      (OPT), OPV or without portal blood occlusion. Liver blood flow (LBF), liver
      damage and regeneration were assessed. The safety limit for the duration of liver
      ischemia was 20 min for OPT and 40 min for OPV in rats with OJ. OPT and OPV
      methods resulted in significantly decreased microvascular LBF in rats with OJ
      from 529.53+/-91.55 laser speckle perfusion units (LSPU) in the control to
      136.89+/-32.32 and 183.99+/-49.25 LSPU, respectively. Liver damage was assessed
      analyzing levels of serum alanine transaminase and direct bilirubin, determining
      interleukin-1beta and tumor necrosis factor-alpha expression and histological
      examination. It was demonstrated that liver damage and caspase-3 and -9
      expression in the liver were substantially reduced in the OPV group compared with
      the OPT group. In addition, the OPV method significantly improved liver
      regeneration in OJ rats, as indicated by increased rates of liver regeneration
      and expression of proliferating cell nuclear antigen and Ki-67 compared with the
      OPT group. Therefore, the OPV method may prolong the duration of portal blood
      occlusion, reduce liver injury and improve liver regeneration by preserving
      hepatic arterial flow during portal blood control in rats with OJ undergoing
      partial hepatectomy. The current study describes a novel technique, which may be
      applied in liver surgery in patients with complex jaundice.

PMID- 30186419
TI  - Effects of imipenem combined with low-dose cyclophosphamide on the intestinal
      barrier in septic rats.
AB  - Anti-infection therapy combined with immunotherapy is one of the important
      research approaches for treating sepsis. However, the combination of anti
      infection and immunotherapy therapeutic agents may have an adverse effect on
      intestinal barrier function. In the present study, it was hypothesized that
      imipenem combined with low-dose cyclophosphamide (CTX) could improve the sepsis
      survival rate compared with imipenem treatment alone. In addition, the
      alterations in the intestinal barrier were investigated and the possible
      mechanisms of altering intestinal barrier function in septic rats treated with
      imipenem combined with low-dose CTX or imipenem alone were explored. To
      investigate the effect of imipenem combined with low-dose CTX on the intestinal
      barrier, the markers of histopathology, intestinal permeability, intestinal
      epithelial apoptosis, cytokines interleukin (IL)-6, IL-10 and tumor necrosis
      factor (TNF)-alpha, and tight junction proteins zonula occludens (ZO)-1, occludin
      and claudin-2, were quantitatively and qualitatively evaluated. The results
      indicated that imipenem combined with low-dose CTX significantly improved the
      survival rate of rats compared with imipenem alone (P<0.05). However, no
      significantly difference between the treatment with imipenem combined with low
      dose CTX and imipenem treatment alone was indicated with regard to
      histopathology, intestinal permeability, intestinal epithelial apoptosis and the
      expression of claudin-2, ZO-1 and TNF-alpha. However, imipenem combined with low
      dose CTX significantly reduced IL-6 and IL-10 expression and significantly
      increased occludin expression compared with imipenem alone (P<0.05). It was
      concluded that imipenem combined with low-dose CTX could improve the survival
      rate of rats with sepsis compared with rats treated with imipenem alone. The
      present findings suggest that imipenem combined with low-dose CTX may cause
      damage to the intestinal barrier function and the mechanism may be associated
      with a reduction in IL-10 expression.

PMID- 30186420
TI  - Intra-articular, single-shot co-injection of hyaluronic acid and corticosteroids
      in knee osteoarthritis: A randomized controlled trial.
AB  - The aim of the present study was to investigate whether the co-injection of
      hyaluronic acid (HA) and corticosteroids (CS) was superior to HA alone in the
      treatment of knee OA. A total of 120 participants with symptomatic knee OA were
      recruited and formed the intention-to-treat population for a 6-month follow-up.
      In the HA group, patients received a single-shot injection of 4 ml HA. In the
      HA&CS group, patients received a co-injection of 3 ml compound betamethasone
      solution and 4 ml HA. Visual analog scale (VAS), Western Ontario and McMaster
      University Osteoarthritis Index (WOMAC) and knee flexion motion were assessed as
      primary outcomes. Patients in the HA&CS group exhibited better pain relief and
      knee function at the time points of week 1, month 1 and month 3 (P<0.05). For the
      last follow-up at month 6, the values did not differ significantly between these
      two groups. Patients in both groups exhibited improvement in pain, knee function,
      and range of motion following injection. For the final follow-up at month 6, the
      mean VAS score, WOMAC score and knee flexion motion were still superior to that
      prior to treatment, but the values did not differ significantly. The co-injection
      of HA and CS provided a rapid improvement in pain relief, knee function, and
      range of motion, but did not differ significantly from that of HA alone in the
      long term effect.

PMID- 30186421
TI  - MicroRNA-144 mediates chronic inflammation and tumorigenesis in colorectal cancer
      progression via regulating C-X-C motif chemokine ligand 11.
AB  - Colorectal cancer (CRC) is one of the most common malignancies worldwide. The aim
      of the present study was to investigate the expression of microRNA-144 (miR-144)
      and C-X-C motif chemokine ligand 11 (CXCL11) in CRC and their association. Data
      from Gene Expression Omnibus (GEO) DataSets were analyzed to obtain the
      expression profile of CXCL11 in CRC. Subsequently, serum samples were collected
      from 65 subjects, including 39 patients with CRC and 26 controls; CRC and
      adjacent normal tissues were collected from all 39 CRC patients and the
      expression of CXCL11 was measured in these specimens. After searching for the
      potential regulator of CXCL11 through bioinformatics analysis, the levels of miR
      144 in the clinical specimens were also detected. Finally, the regulatory
      association between miR-144 and CXCL11 was certified via the dual-luciferase
      reporter assay. Microarray data and bioinformatics analysis demonstrated that
      CXCL11 was significantly upregulated in CRC tissues and miR-144 was a potential
      regulator of CXCL11. In line with this finding, the expression of CXCL11 was
      significantly increased in the serum and tumor samples of patients with CRC,
      while that of miR-144 was downregulated. Dual-luciferase reporter assay revealed
      that miR-144 directly targets the 3'-untranslated region of CXCL11 mRNA to
      regulate its expression. These results demonstrated that enhanced CXCL11
      expression in patients with CRC was associated with reduced miR-144 expression.
      The results of the present study may indicate a novel regulatory role of miR-144
      in CRC through CXCL11 downregulation.

PMID- 30186422
TI  - Ultrasound-guided continuous fascia iliaca compartment block for pre-operative
      pain control in very elderly patients with hip fracture: A randomized controlled
      trial.
AB  - The present study presented the results of a prospective, randomized controlled
      trial. The present study enrolled 98 very elderly patients with hip fractures,
      complicated with at least one cardiovascular, neurological or pulmonary disease,
      of whom 10 patients were excluded. A total of 88 patients were randomly assigned
      into 2 groups: i) The control group, receiving traditional analgesia including 50
      mg Tramadol and 500 mg paracetamol orally three times a day from admission to
      surgery; and ii) the study group, receiving ultrasound-guided continuous fascia
      iliaca compartment block (CFICB), a single 50 ml 0.4% ropivacaine injection with
      continuous infusion of 0.2% ropivacaine at a dose of 5 ml/h from admission to
      surgery. The primary outcome measure of pain relief or pain intensity was
      assessed preoperatively and up to 48 h postoperatively using a visual analog
      scale (VAS). The results of the present study indicated that in the preoperative
      period, in the morning of the day of surgery, the VAS pain at rest scores were
      lower in the study group compared with the control group (P=0.023). The VAS
      passive movement scores of the study group were also significantly lower compared
      with the control group 1 h following analgesia at the time of admission (P<0.05)
      and in the morning of the day of surgery (P<0.05). Scores for patients'
      satisfaction with the analgesic regimen in the preoperative period were greater
      in the study group compared with the control group (P<0.001). There was no
      difference in analgesia-associated side effects between groups. Duration of
      hospital stay of patients in the control group was significantly longer compared
      with the study group (P=0.001). Patients in the study group were less likely to
      have increased complications compared with patients in the control group over the
      N2-N4 period (from preoperative period to after surgery; P=0.016). The present
      study concluded that ultrasound guided CFICB was an effective method of providing
      analgesia for very elderly (>=80 years old) with hip fracture.

PMID- 30186423
TI  - Effects of comprehensive pulmonary rehabilitation therapy on pulmonary functions
      and blood gas indexes of patients with severe pneumonia.
AB  - In this study we try to observe the effects of comprehensive pulmonary
      rehabilitation therapy on pulmonary functions and blood gas indexes of patients
      with severe pneumonia during mechanical ventilation. A total of 120 patients with
      severe pneumonia were selected and divided into the experimental group (n=60) and
      the control group (n=60) through a random number table. Conventional therapy for
      severe pneumonia was applied to patients in both groups, and the experimental
      group was additionally treated with comprehensive pulmonary rehabilitation
      therapy, including warming-up exercise before training, respiratory function
      exercise, respiratory muscle training, health education, psychological support
      and nutritional intervention. The pulmonary function indexes, blood gas indexes,
      Borg index scores and 6-min walk distance (6MWD) of the two groups of patients
      were evaluated before treatment and at 6 months after treatment, respectively. In
      the control group, there were statistically significant differences only in
      forced expiratory volume in 1 sec (FEV1), ratio of FEV1 to forced vital capacity
      (FEV1/FVC), partial pressure of O2 (PaO2), arterial partial pressure of carbon
      dioxide (PaCO2), Borg index and 6MWD after treatment compared with those before
      treatment (P<0.05); as for intra-group comparisons, there were no significant
      improvements in other indexes compared with those before treatment, and the
      differences were not statistically significant (P>0.05). In the experimental
      group, all the indexes after treatment were statistically different from those
      before treatment and those after treatment in the control group (P<0.05); with
      regard to comparisons of the indexes between the control group and the
      experimental group, the differences were significant (P<0.05). Comprehensive
      pulmonary rehabilitation therapy is conducive to improving the pulmonary
      functions and blood gas indexes of patients with severe pneumonia during
      mechanical ventilation.

PMID- 30186424
TI  - Expression and significance of autophagy genes LC3, Beclin1 and MMP-2 in
      endometriosis.
AB  - Expression of autophagy-related proteins, microtubule-associated protein light
      chain 3 (LC3) and Beclin1, and matrix metalloproteinase-2 (MMP-2) was
      investigated in serum and peritoneal fluid of patients with endometriosis (EM).
      The messenger ribonucleic acid (mRNA) expression levels of MMP-2, LC3 and Beclin1
      in endometrial tissues of EM patients and correlation of these genes with EM and
      their significance were evaluated. The serum, peritoneal fluid and endometrial
      tissues of 84 patients treated in The First Affiliated Hospital of Qiqihar
      Medical University (Qiqihar, China) from March 2016 to March 2017 were collected.
      The serum, peritoneal fluid and endometrial tissues of 42 EM patients were used
      as the experimental group, while those of 42 non-EM patients were used as the
      control group. The levels of LC3, Beclin1 and MMP-2 in serum and peritoneal fluid
      of EM patients and non-EM patients were quantitatively detected via enzyme-linked
      immunosorbent assay (ELISA), followed by comparative analysis based on data in
      both groups. In addition, mRNA expression of LC3, Beclin1 and MMP-2 in the
      endometrium in both groups were detected via reverse transcription-quantitative
      polymerase chain reaction (RT-qPCR), and differences in expression of these genes
      between the groups were analyzed and evaluated. Correlation of LC3, Beclin1 and
      MMP-2 with EM was explored. Results of ELISA showed that levels of LC3 and
      Beclin1 in the EM group were significantly lower than those in the control group,
      while levels of MMP-2 in serum and peritoneal fluid of the EM group were
      significantly higher than those in the control group (P<0.05). Results of RT-qPCR
      revealed that mRNA expression of LC3 and Beclin1 in the endometrium of patients
      in the EM group were obviously decreased compared with those in the control
      group, while the expression of MMP-2 was high, and differences in expression were
      statistically significant (P<0.05). The expression of MMP-2 is high, and
      expression of LC3 and Beclin1 is low in serum, peritoneal fluid and endometrium
      of EM patients, and investigating the expression of MMP-2, LC3 and Beclin1 in EM
      is helpful to further clarify the pathogenesis of EM, and guide the clinical
      diagnosis and treatment.

PMID- 30186425
TI  - Reduced hepcidin level features osteoporosis.
AB  - Osteoporosis (OP) is a common serious skeletal disorder marked by increased risk
      of bone fracture due to fragility. OP has been taken to be a disease linked with
      abnormal calcium metabolism that alone is obviously insufficient to explain the
      development of OP. Iron overload has been associated with the development of OP
      and increasing studies have suggested the association. However, direct evidence
      for this has not been clinically established. To this end, using the Roche
      biochemical autoanalyzer, we detected the concentration of iron, soluble
      transferrin receptor 2 (TFR2), and hepcidin, a key peptide regulating iron
      homeostasis, in the sera from patients with OP. It was shown that the iron and
      TFR2 concentration was markedly higher than that of healthy control; whereas the
      concentration of hepcidin was markedly lower than that in control. In addition,
      to pilot explore the underlying mechanism by which hepcidin was downregulated, we
      present that hepcidin can directly interact with TFR2 using immunoprecipitation.
      The present study first established the direct biochemical evidence for the
      involvement of hepcidin in the pathogenesis of OP, indicating that the
      upregulation of hepcidin could be used as a novel alternative therapeutic
      strategy in the management of OP.

PMID- 30186426
TI  - Baicalin and puerarin reverse epithelial-mesenchymal transition via the TGF
      beta1/Smad3 pathway in vitro.
AB  - Epithelial-mesenchymal transition (EMT) occurs in the development of fibrosis and
      carcinogenesis. EMT is associated with chronic liver injury. Evidence shows that
      hepatocytes undergo EMT in the adult liver. The Qinggan Huoxue Recipe (QGHXR), a
      Traditional Chinese Medicinal formula, shows a range of pharmacological effects
      in treating alcoholic liver disease. The present study aimed to investigate the
      effect of four major components of QGHXR, baicalin, salvianic acid, puerarin and
      saikosaponin, on EMT in vitro, and to elucidate the potential mechanism of QGHXR
      against EMT via the transforming growth factor-beta1 (TGF-beta1)/Smads signaling
      pathway. EMT models were established using LO2 hepatocytes and HepG2 cells
      treated with acetaldehyde in vitro. Acetaldehyde presented a mesenchymal cell
      characteristic in hepatocytes, accompanied by an increased expression of
      mesenchymal markers, including vimentin and fibronectin, and decreased E
      cadherin. Baicalin and puerarin abrogated the increased expression of vimentin
      and fibronectin, and rescued E-cadherin expression in acetaldehyde-treated
      hepatocytes. It was further demonstrated that baicalin and puerarin reduced the
      gene expression of snail, TGF-beta1 and Smad3. A decreased expression of tight
      function markers, including ZO-1, occludin and claudin, were also found in the
      acetaldehyde-treated hepatocytes. Barcacin regulated the mRNA level of TGF-betal
      and snail, and then suppressed the EMT process. This was accompanied by an
      increased mRNA level of E-cadherin and decreased levels of vimentin and
      fibronectin, but no significant differences in of Smad3, occludin, ZO-1 and
      claudin were observed. Puerarin regulated the mRNA level of TGF-betal, Smad3 and
      snail, suppresing the EMT process, which was accompanied by an increased mRNA
      level of E-cadherin and decreased levels of vimentin and fibronectin, along with
      increased levels of occludin, ZO-1 and claudin. When the snail gene was silent,
      barcacin and puerarin did not show significant effects in the acetaldehyde
      treated cells. The results presented a novel mechanism through which baicalin and
      puerarin modulated hepatocyte EMT to improve liver fibrosis.

PMID- 30186427
TI  - The role of Wnt signaling pathway in atherosclerosis and its relationship with
      angiogenesis.
AB  - Expression and function of Wnt signaling pathway in rats with atherosclerosis
      (AS) were investegated. The AS model of rats was established after 8-week
      continuous feeding of a high-fat diet, with normal rats as the control. Blood was
      taken from the carotid artery to detect the level of blood lipid. Aortic slices
      were made to observe the pathological changes of the aorta after the rats were
      sacrificed. Enzyme-linked immunosorbent assay kits were used to detect the
      contents of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha).
      Western blot analysis and semi-quantitative reverse transcription-polymerase
      chain reaction (RT-PCR) were performed to detect the expression levels of related
      proteins and mRNA in rat Wnt signaling pathway. Correlation analysis between the
      protein expression level of vascular endothelial growth factor (VEGF) and that of
      Wnt1 was conducted. Aortic slices showed that the ratio of intima thickness to
      media thickness of the rats in the model group was higher than that of in the
      control group (P<0.01). Blood lipid and the contents of IL-6 and TNF-alpha of the
      rats in the model group were higher than those of the rats in the control group
      (P<0.01). Semi-quantitative RT-PCR indicated that mRNA expression levels of Wnt1,
      beta-catenin and dickkopf1 in the aorta of rats in the model group were increased
      compared with those of control group (P<0.01). The results of western blot
      analysis revealed that the protein expression levels of Wnt1, beta-catenin, DKK1
      and VEGF of the rats in the model group were remarkably higher than those of the
      control group (P<0.01). The level of VEGF protein was positively correlated with
      that of Wnt1 (P<0.05, r=0.7810). The activation of Wnt signaling pathway in the
      aorta of the rats with AS can induce the expression of relevant inflammatory
      cytokines. It has the effects of promoting the progression of AS and accelerating
      angiogenesis.

PMID- 30186428
TI  - Correlation between the expression of inflammatory cytokines IL-6, TNF-alpha and
      hs-CRP and unfavorable fetal outcomes in patients with pregnancy-induced
      hypertension.
AB  - The expression of inflammatory factors, tumor necrosis factor-alpha (TNF-alpha),
      interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hs-CRP), in
      patients with pregnancy-induced hypertension (PIH) was investigated, to analyze
      correlation of expression levels of these factors in patients with unfavorable
      fetal outcome. A total of 100 patients diagnosed with PIH treated in Jining First
      People's Hospital (Jining, China) from January 2012 to October 2017 were selected
      as the experimental group, while 100 normal pregnant women during the same period
      were selected as the control group. Results showed that the levels of IL-6, TNF
      alpha and hs-CRP in patients with PIH were significantly higher than those in
      normal pregnant women (p<0.01). There were significant differences in levels of
      IL-6, TNF-alpha and hs-CRP among patients with hypertension in different degrees.
      The expression levels of IL-6, TNF-alpha and hs-CRP in PIH patients with
      favorable pregnancy outcome were lower than those in patients with unfavorable
      pregnancy outcome (p<0.05). Moreover, the expression levels of IL-6, TNF-alpha
      and hs-CRP had a linearly positive correlation with systolic blood pressure in
      PIH patients. Age, height and weight had no significant correlation with
      unfavorable pregnancy outcome of PIH patients (p>0.05). Finally, inflammatory
      factors (TNF-alpha, IL-6 and hs-CRP) and blood pressure were obviously and
      positively correlated with unfavorable pregnancy outcome of PIH patients
      (p<0.05). In conclusion, the expression of inflammatory factors (TNF-alpha, IL-6
      and hs-CRP) in PIH patients are positively correlated with the systolic blood
      pressure and unfavorable fetal outcome of patients, which can be used as indexes
      of prognosis evaluation of PIH patients.

PMID- 30186429
TI  - Nerve growth factor and substance P may be involved in moist exposed burn
      ointment-mediated chronic refractory wound healing.
AB  - Moist exposed burn ointment (MEBO) is becoming increasingly popular in China as
      it shortens wound-healing time and reduces scar formation. However, its exact
      mechanism in mediating the wound-healing process is not yet clear. In the present
      study a total of 90 healthy adult male Wistar rats of specific-pathogen-free
      grade were divided equally into a control group, wound group, MEBO group,
      recombinant bovine basic fibroblast growth factor (rb-bFGF) group and sham
      operation group. Wound healing was observed from the extracted granulation
      tissues and recorded at three time points on 3, 7 and 14 days. Different levels
      of tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) in tissue
      homogenate were detected using ELISA. Western blot analysis and quantitative PCR
      were used to detect the expression of nerve growth factor (NGF), substance P (SP)
      as well as tyrosine kinase A (TrkA) receptor protein and the corresponding mRNA
      levels in granulation tissue. It was observed that the wound healing progressed
      faster in the MEBO and rb-bFGF groups compared with the wound group (P<0.01). TNF
      alpha and IL-6 had an upward-downward trend at three time points, with the wound
      group demonstrating the most obvious increase (P<0.01). NGF and SP mRNA and
      protein levels in granulation tissue in MEBO, rb-bFGF and sham operation groups
      reached their highest levels on day 7 and then decreased on day 14. The
      expression level of TrkA was also measured simultaneously and its expression
      pattern was similar to that of NGF and SP. These results suggested that MEBO may
      promote nerve repair and accelerate wound healing through mediating the
      expression levels of NGF and SP, as well as TrkA.

PMID- 30186430
TI  - Hybrid surgery for an arteriovenous malformation fed by an accessory middle
      cerebral artery and drained by a developmental venous anomaly: A case report and
      literature review.
AB  - An accessory middle cerebral artery (AMCA), which mainly acts in the collateral
      circulation of the middle cerebral artery (MCA), is a rare anatomic malformation.
      Similar to other intracranial vessels, cerebrovascular disease can occur in the
      AMCA. However, the development of an arteriovenous malformation (AVM) in the AMCA
      is very rare, especially in conjuction with developmental venous anomalies
      (DVAs). Here, a rare case of an AMCA combined with an AVM and a DVA was reported.
      The patient was a 47-year-old female with intracranial hemorrhage at symptom
      onset. CT and MRI showed lesions in the left Sylvian fissure and insula
      accompanied by hemorrhage. DSA suggested a left AMCA; an AVM of the AMCA was
      located in the deep Sylvian fissure. The AVM was diffusely developed and drained
      into the DVA. The operation was performed in a hybrid operating room. The major
      feeding artery of the AVM, which was derived from the AMCA, was clipped, then the
      AVM and DVA were subsequently removed. Intraoperative DSA showed that the AVM and
      DVA were radically removed. A pathological examination confirmed the presence of
      an AVM. The patient recovered well and was discharged. Therefore, as highlighted
      in this case report, rare AVMs can be found in AMCAs and can even occur
      simultaneously with a DVA. Hybrid surgical treatment can be used to remove AVMs
      and can lead to an improved prognosis.

PMID- 30186432
TI  - Therapeutic effect of berberine on renal ischemia-reperfusion injury in rats and
      its effect on Bax and Bcl-2.
AB  - This study aimed to investigate the therapeutic effect of berberine on renal
      ischemia-reperfusion injury in rats and its effect on Bax and Bcl-2. Sixty adult
      SD rats were randomly divided into four groups: control group A, renal ischemia
      reperfusion group B, berberine group C and berberine + exendin-(9-39) treatment
      group D. In group A, right kidney was resected and left renal pedicle was
      separated, but left renal artery was not blocked. Renal ischemia-reperfusion
      model was established in other groups. Rats in group C were not subjected to any
      treatment after model construction. Rats in group C and D were subjected to
      intraperitoneal injection of berberine 7 days before the experiment. Besides
      that, intraperitoneal injection of exendin-(9-39) was performed at day 1 and 4
      after model construction. Automatic biochemical analyzer was used to measure
      serum creatinine (SCr) and blood urea nitrogen (BUN). Malondialdehyde (MDA) in
      renal cortex was measured by enzyme-linked immunosorbent assay and contents of
      Bax and Bcl-2 in renal tissue were measured by western blot analysis. Apoptosis
      of rat renal cells was detected by TUNEL assay. The results showed that levels of
      SCr, BUN, MDA and Bax were significantly higher in group B than in other groups
      (P<0.05). Levels of Bcl-2 in group B were significantly higher than those in
      group A but significantly lower than those in group C and D. Compared with group
      A, apoptosis of renal cells was more severe in group B. Compared with group B,
      apoptosis of renal cells was significantly improved in group C and D, but was
      still more severe than that in group A. In conclusion, berberine can effectively
      improve renal function in rats with renal ischemia-reperfusion injury by
      inhibiting Bax expression and promoting Bcl-2 expression.

PMID- 30186431
TI  - H1N1 influenza virus epitopes classified by monoclonal antibodies.
AB  - Epitopes serve an important role in influenza infection. It may be useful to
      screen universal influenza virus vaccines, analyzing the epitopes of multiple
      subtypes of the hemagglutinin (HA) protein. A total of 40 monoclonal antibodies
      (mAbs) previously obtained from flu virus HA antigens (development and
      characterization of 40 mAbs generated using H1N1 influenza virus split vaccines
      were previously published) were used to detect and classify mAbs into distinct
      flu virus sub-categories using the ELISA method. Following this, the common
      continuous amino acid sequences were identified by multiple sequence alignment
      analysis with the GenBank database and DNAMAN software, for use in predicting the
      epitopes of the HA protein. Synthesized peptides of these common sequences were
      prepared, and used to verify and determine the predicted linear epitopes through
      localization and distribution analyses. With these methods, nine HA linear
      epitopes distributed among different strains of influenza virus were identified,
      which included three from influenza A, four from 2009 H1N1 and seasonal
      influenza, and two from H1. The present study showed that considering a
      combination of the antigen-antibody reaction specificity, variation in the
      influenza virus HA protein and linear epitopes may present a useful approach for
      designing effective multi-epitope vaccines. Furthermore, the study aimed to
      clarify the cause and pathogenic mechanism of influenza virus HA-induced flu, and
      presents a novel idea for identifying the epitopes of other pathogenic
      microorganisms.

PMID- 30186433
TI  - Effect of JAK2/STAT3 signaling pathway on liver injury associated with severe
      acute pancreatitis in rats.
AB  - Janus kinase/signal transducers and activators of transcription (JAK/STAT)
      signaling constitutes one of the major pathways for cytokine signal transduction.
      However, the role of the JAK2/STAT3 pathway in liver injury during severe acute
      pancreatitis (SAP) remains unclear. The aim of this study was to investigate the
      role of the JAK2/STAT3 signaling pathway in liver injury after SAP. In the
      present study 64 male Sprague-Dawley rats were randomly divided into four groups:
      Control, AG490 (inhibition of JAK2), SAP and SAP with AG490. SAP was induced by
      retrograde infusion of 4% sodium taurocholate into the biliopancreatic duct. The
      activities of amylase (AMY) and liver enzymes were measured in serum. Livers and
      pancreas were isolated for measurements of histological damage. Blood and liver
      samples were taken for the measurement of TNF-alpha, IL-6 and IL-18
      concentrations. The expression levels of JAK2 and STAT3 in liver tissue were
      detected by immunohistochemical staining and western blotting. The results
      demonstrated that amylase and liver enzymes were higher in the SAP groups
      compared with the control, AG490 and AG490-treated groups. The serum levels of
      TNF-alpha, IL-6 and IL-18 were effectively increased in the SAP groups, whereas
      they were reduced by AG490. Interestingly, JAK2 and STAT3 protein expression
      levels were significantly increased following induction of SAP and were
      significantly decreased in the AG490-pretreated groups. Administration of AG490
      decreased the activity of pro-inflammatory cytokines and significantly attenuated
      SAP associated-liver injury in the rats. These results suggested that the
      mechanism may relate to the inhibition of TNF-alpha, IL-6 and IL-18, and
      inhibiting excessive JAK2 and STAT3 activation, and may play a crucial role in
      the liver injury associated with SAP.

PMID- 30186434
TI  - The relationship between insulin resistance, adiponectin and C-reactive protein
      and vascular endothelial injury in diabetic patients with coronary heart disease.
AB  - Relationship between insulin resistance, adiponectin and C-reactive protein and
      vascular endothelial injury in diabetic patients with coronary heart disease
      (CHD) was investigated. Clinical data of 72 patients with diabetes mellitus
      diagnosed in Weifang People's Hospital (Weifang, China) from October 2015 to
      January 2017 were retrospectively analyzed. Thirty patients were combined with
      CHD and 42 patients were not. There were 43 males and 29 females. General
      information and clinical data including age, sex, duration of diabetes mellitus,
      biochemical indicators, fasting insulin levels, CRP, insulin resistance index,
      arterial lesions of coronary angiography and Gensini scores were collected. The
      levels of FINS, FPG, HOMA-R and CPR were significantly higher, and the level of
      ADPN was significantly lower in diabetes complicated with CHD group than that
      without CHD group (P<0.05). Incidence of single coronary artery disease and mild
      coronary lesion were significantly lower, and incidences of double and triple
      lesions were significantly higher in diabetes complicated with CHD group than
      that without CHD group (P<0.05). Gensini score was significantly higher in
      diabetes complicated with CHD group than that without CHD group (P<0.05);
      Analysis of the correlation showed that CRP (r=0.422, P=0.001) and insulin
      resistance index (r=0.828, P=0.001) were positively correlated with Gensini
      score, while the adiponectin level was negatively correlated with Gensini score
      (r= -0.719, P<0.001). Logistic regression analysis showed that FINS, ADPN, HOMA
      R, CPR, duration of diabetes mellitus and BMI had independently predictive value
      for diabetes complicated with CHD (P<0.05). Serum adiponectin, insulin resistance
      and CPR levels are closely related to diabetes mellitus combined with coronary
      heart disease, and can affect the degree of vascular endothelial injury in
      coronary heart disease.

PMID- 30186435
TI  - Chronic pulmonary complications associated with toxic epidermal necrolysis: A
      case report and literature review.
AB  - Patients with toxic epidermal necrolysis (TEN) are known to experience various
      complications. Although pulmonary complications are commonly observed, they
      typically manifest in an acute form. By contrast, chronic complications are quite
      rare, and little is known with regard to their incidences or clinical
      manifestations. The present study reports the case of a 29-year-old female
      patient who suffered from TEN. At the onset of the disease, the patient exhibited
      no pulmonary impairment; however, 1 month after recovering from TEN, the patient
      developed severe obstruction and a mild diffusion defect. A diagnosis of
      bronchiolitis obliterans was determined, and the patient was treated with
      antibiotics, inhaled corticosteroids, anticholinergic agents, and
      bronchodilators. At the last follow-up, the patient was alive, but with a stable
      airway obstruction.

PMID- 30186436
TI  - The biological effect and mechanism of the Wnt/beta-catenin signaling pathway on
      malignant melanoma A375 cells.
AB  - The present study aimed to determine the influence of the Wnt/beta-catenin
      signaling pathway on the proliferation, invasion, migration and apoptosis of
      malignant melanoma (MM) A375 cells. beta-catenin interfering lentivirus liquid
      (beta-catenin-RNAi-LV) and empty vector lentivirus liquid (beta-catenin-negative
      LV) were used to infect A375 cells. Infected cells were obtained and marked as
      A375-RNA interference (A375-RNAi) or A375-negative, respectively. Western
      blotting was used to measure the expression of beta-catenin in infected cells and
      uninfected cells were utilized as a control. An MTT assay was adopted to measure
      cell proliferation and the clone formation of cells was assessed. In addition,
      the Transwell method was used to detect cell invasion and migration in vitro and
      flow cytometry was utilized to determine cell apoptosis. Western blot analysis
      demonstrated that beta-catenin was highly expressed in uninfected A375 cells but
      exhibited reduced expression in A375-RNAi cells. These results indicate that beta
      catenin expression is effectively silenced by beta-catenin-RNAi-LV. The
      proliferative and clone forming abilities of A375-RNAi cells were impaired
      compared with A375-negative and A375 cells. Additionally, the apoptosis rate was
      increased and the invasion and migration of A375-RNAi cells was decreased.
      However, no significant differences were identified in the proliferation, clone
      formation, apoptosis rate, invasion and migration of A375-negative cells compared
      with A375 cells. Therefore, the current study demonstrated that the inhibition of
      beta-catenin expression or activity inhibits cell proliferation and invasion and
      migration, further downregulating the expression of anti-apoptotic genes and
      accelerating cellular apoptosis.

PMID- 30186437
TI  - MicroRNA-21 promotes the proliferation, migration and invasion of non-small cell
      lung cancer A549 cells by regulating autophagy activity via AMPK/ULK1 signaling
      pathway.
AB  - The present study investigated the expression of microRNA (miR)-21 in non-small
      cell lung cancer (NSCLC) tissues, its biological functions and mechanism of
      autophagy regulation. A total of 46 patients with NSCLC were enrolled in the
      present study. To measure the expression of miR-21, reverse transcription
      quantitative polymerase chain reaction (RT-qPCR) was employed. NSCLC A549 cells
      were transfected with miR-negative control (NC), miR-21 mimics or inhibitor. The
      CCK-8 assay was used to investigate the proliferation of A549 cells. To study
      migration and invasion abilities of A549 cells, The Transwell assay was
      performed. In addition, to determine the expression levels of ULK1, LC3B,
      AMPKalpha, p-AMPKalpha and p62 proteins, western blotting was conducted and laser
      confocal microscopy was performed to observe the formation of autophagosomes in
      A549 cells. To explore whether miR-21 regulates the biological functions of A549
      cells via autophagy, an autophagy inhibitor, 3-MA, or agonist, rapamycin, were
      used in a rescue assay. Results indicated that miR-21 expression in NSCLC tissues
      was enhanced, and closely correlated with the occurrence and development of
      NSCLC. In vitro experiments showed that miR-21 mimics promoted the proliferation,
      migration and invasion of A549 cells, while miR-21 inhibitor inhibited these
      biological functions. Western blotting indicated that miR-21 upregulated
      autophagy marker LC3BII protein, but downregulated p62 protein. Laser confocal
      microscopy showed that miR-21 activated autophagy of A549. Rescue experiments
      indicated that autophagy reversed the effect of miR-21 on the proliferation,
      migration and invasion of A549 cells. Western blotting data suggested that
      autophagy-related AMPK/ULK1 signaling pathway was activated by miR-21, and
      interference or overexpression of ULK1 reversed the biological functions of miR
      21. The present study demonstrated that miR-21 expression in NSCLC tissues was
      upregulated and positively correlated with lymphatic metastasis and clinical
      staging. In addition, miR-21 regulated autophagy activity of NSCLC A549 cells via
      AMPK/ULK1 signaling pathway, and promoted the proliferation, migration and
      invasion of NSCLC A549 cells.

PMID- 30186438
TI  - Improved heart failure by Rhein lysinate is associated with p38MAPK pathway.
AB  - The present study aimed to explore the role of Rhein lysinate (RHL) in neonatal
      rat ventricular myocytes (NRVMs) and congestive heart failure induced by co
      arctation of the abdominal aorta. Male Sprague-Dawley rats were divided into 3
      groups randomly: co-arctation of abdominal aorta group (A group, n=10), sham
      operation group (SH group, n=10) and RHL treatment rats (A+RHL group, n=10). To
      establish an in vitro oxidative stressed cardiomyocyte model, NRVMs were treated
      with 10 uM H2O2 for 24 h. MTT assay indicated that H2O2 treatment reduced primary
      cardiomyocyte viability in a time- and dose- dependent manner, whereas RHL
      abolished the detrimental effects of H2O2, indicating a protective role of RHL.
      Further study demonstrated that H2O2-induced reactive oxygen species (ROS)
      production was reversed by RHL. Then, TUNEL staining was carried out and the
      results revealed that H2O2 markedly enhanced primary cardiomyocyte apoptosis.
      Conversely, RHL incubation decreased H2O2-induced cell apoptosis, indicating the
      protective role of RHL in primary cardiomyocytes. Furthermore, abnormal p38
      activation was identified in the failed heart. Notably, treatment with RHL
      reduced p38 activation. In addition, RHL significantly enhanced the expression of
      anti-apoptotic protein, B cell lymphoma (Bcl)-2, however markedly reduced the
      protein level of Bcl-2 associated X, apoptosis regulator in primary
      cardiomyocytes, indicating its anti-apoptotic role in the cardiac setting.
      Overall, RHL protects heart failure primarily by reducing ROS production and
      cardiomyocyte apoptosis via suppressing p38 mitogen activated protein kinase
      activation.

PMID- 30186440
TI  - Hemophagocytic lymphohistiocytosis presenting with annular erythema multiforme
      like eruptions in a patient with angioimmunoblastic T cell lymphoma: A case
      report.
AB  - Angioimmunoblastic T cell lymphoma (AITL)-associated hemophagocytic
      lymphohistiocytosis (HLH) rarely occurs with annular erythema multiforme-like
      rashes. The present case report describes a patient who was misdiagnosed with
      erythema multiforme at an early stage of the disease due to annular erythema
      multiforme-like eruptions. However, antihistamine treatment was ineffective. The
      patient progressed rapidly with high fever, hepatosplenomegaly and pharyngitis.
      The number of copies of Epstein-Barr virus DNA continuously increased.
      Accompanied by the swelling of lymph nodes, the blood cell count decreased.
      Further bone-marrow examination and biopsy of the lymph nodes were conducted. The
      patient was eventually diagnosed with AITL-associated HLH, and treated with
      etoposide together with cyclophosphamide, doxorubicin, vincristine and
      prednisolone. The patient was successfully treated with several courses of
      chemotherapy. In view of the fact that AITL-associated HLH with annular erythema
      multiforme-like rashes is relatively rare worldwide and is associated with a high
      mortality rate, the data on previous cases were reviewed with the hope of
      providing clinical bases for early diagnosis and treatment of AITL-associated
      HLH.

PMID- 30186441
TI  - Ultrasonic evaluation of congenital vaginal oblique septum syndrome: A study of
      21 cases.
AB  - The aim of the present study was to investigate the ultrasound features and
      classify the lesion types of congenital vaginal oblique septum syndrome (CVOS) in
      21 patients prior to surgery. Grey-scale pelvic ultrasound was performed to
      evaluate the uterus, vagina and kidneys in 21 patients with suspected CVOS.
      Ultrasound features, including the presence of a double uterus, hematocolpos
      masses and renal absence, in CVOS types I, II and III were studied and compared
      with intra-operative results and the results of surgery. Ultrasound identified
      the presence of double uteruses and cervices with ipsilateral renal agenesis on
      the oblique septum side in all 21 patients. There were 14 hematocolpos lesions on
      the right and 7 on the left of the vagina. Type I CVOS was diagnosed in 15
      patients with a large hematocolpos mass (volume, 64-268 ml) and these diagnoses
      were confirmed by surgery. Furthermore, there were 4 patients with type II and 2
      patients with type III CVOS exhibiting small hematocolpos lesions (volume, 5-36
      ml) identified by ultrasound, which were all confirmed by surgery. Therefore,
      ultrasound imaging is useful tool to evaluate the abnormal features of CVOS and
      determine the type of CVOS in patients prior to surgical intervention.

PMID- 30186439
TI  - Impact of weight cycling on CTRP3 expression, adipose tissue inflammation and
      insulin sensitivity in C57BL/6J mice.
AB  - Impacts of weight cycling on C1q/tumor necrosis factor (TNF)-related protein-3
      (CTRP3) expression, adipose tissue inflammation and insulin sensitivity in
      C57BL/6J mice were evaluated in the current study. A total of 30 male C57Bl/6J
      mice were divided randomly into three groups; normal control (n=10), high-fat
      diet (OB, n=10) and weight cycling (WC, n=10), which were fed with high-fat diet
      in the first and last 8 weeks and regular chow in between. Systemic glucose
      metabolic status and insulin sensitivity were detected by intraperitoneal glucose
      tolerance test and hyperinsulinemic-euglycemic clamp, respectively. Blood levels
      of interleukin (IL)-6 and TNF-alpha were determined using ELISA. Relative CTRP3,
      IL-6, TNF-alpha and glucose transporter (GLUT)4 mRNA expression in adipose tissue
      was detected using reverse transcription-quantitative polymerase chain reaction
      assays. Relative CTRP3, phosphatidylinositide 3-kinases (PI3K) and protein kinase
      B (PKB; Ser473) protein expression were detected by western blot analysis. Area
      under the curve of glucose and glucose infusion rate of the WC group were
      significantly increased compared with the OB group (P<0.01). CTRP3 mRNA and
      protein levels of the WC group were significantly decreased by 20.3 and 23.1%,
      respectively, compared with the OB group (P<0.01). IL-6 and TNF-alpha protein
      plasma levels and gene expression in adipose tissue of the WC group were
      significantly increased compared with the OB group (P<0.01). Expression and
      phosphorylation of insulin signaling molecules PI3K and PKB (Ser473),
      respectively and GLUT4 gene expression in adipose tissue of the WC group were
      significantly decreased compared with the OB group (P<0.01). In conclusion,
      weight cycling impaired glucose metabolism and insulin sensitivity by decreasing
      CTRP3, PI3K, phosphorylated-PKB (Ser473) and GLUT4 expression, and increasing IL
      6 and TNF-alpha levels.

PMID- 30186442
TI  - Specific matrix metalloproteinases and calcification factors are associated with
      the vulnerability of human carotid plaque.
AB  - The rupture of atherosclerotic plaque provokes the majority of acute
      cerebrovascular events. Studies have demonstrated that various matrix
      metalloproteinases (MMPs) may promote atherosclerotic plaque progression and
      rupture. However, results have been incongruous and the mechanisms of this remain
      obscured. Therefore, in the current study, carotid plaques were characterized by
      assessing the levels of MMPs and calcification factors, and evaluating their
      association with plaque vulnerability. Human carotid plaques were obtained from
      carotid endarterectomies, and classified into stable and vulnerable groups by
      ultrasonography and histological analyses. The mRNA and protein levels of MMPs,
      vascular endothelial growth factor (VEGF), bone sialoprotein 2 (BSP) and
      osteopontin were investigated by reverse transcription-quantitative polymerase
      chain reaction and western blotting, respectively. Immunohistochemistry was used
      to localize MMP-2 and MMP-14 in stable and vulnerable plaques. The activation of
      various associated signaling pathways was also investigated using western
      blotting. The mRNA levels of MMP-2, -7, -9 and -14 were elevated in vulnerable
      plaques, among which expression of MMP-2 and -14 were the highest. Consistent
      with the mRNA levels, the protein levels of MMP-2 and -14 were also elevated.
      Immunohistochemistry also demonstrated positive staining of MMP-2 and MMP-14 in
      vulnerable plaques. Factors that indicate neovascularization and calcification,
      including VEGF and BSP, were concurrently elevated in vulnerable plaques. In
      addition, the protein levels of extracellular regulated kinase (ERK) and protein
      kinase C (PKC) were upregulated in vulnerable plaques. The current study provides
      novel insights into the MMP profiles of vulnerability plaques, and may assist in
      the development of novel methods for the diagnosis of plaque vulnerability and
      the prevention of plaque rupture.

PMID- 30186443
TI  - Knockdown of BACE1-AS by siRNA improves memory and learning behaviors in
      Alzheimer's disease animal model.
AB  - Alzheimer's disease (AD) is a devastating neurodegenerative disease that causes
      progressive damage to neurons. Emerging evidence has demonstrated that long non
      coding RNAs (lncRNAs) serve an important role in many neurological diseases, such
      as AD. beta-secretase 1 (BACE1)-antisense transcript (BACE1-AS) was identified as
      a conserved non-coding antisense BACE1. Previous reports stated that BACE1-AS
      positively regulated BACE1 mRNA and subsequently BACE1 protein expression in
      vitro and in vivo. However, whether BACE1-AS is able to regulate memory and
      learning behaviors remains to be elucidated. In the present study, the role of
      lncRNA BACE1-AS on memory and learning was investigated. It was demonstrated that
      lncRNA BACE1-AS expression was highly expressed in blood samples from AD
      patients, and also upregulated in peripheral blood samples and hippocampi from an
      AD animal model. Knockdown of BACE1-AS by short interfering RNA increased the
      primary hippocampal neurons proliferation in vitro. Knockdown of BACE1-AS
      mediated by lentivirus in vivo improved the memory and learning behaviors of
      SAMP8 mice, inhibited BACE1 and amyloid precursor protein production, and
      phosphorylation of tau protein in hippocampi. Therefore, the present findings
      suggested that BACE1-AS may be a potential target for management of memory loss
      related diseases, such as AD.

PMID- 30186444
TI  - Computerized tomography features and clinicopathological analysis of Kimura
      disease in head and neck.
AB  - The aim of the current study was to discuss and analyze computerized tomography
      (CT) features and clinicopathological characteristics of patients with Kimura
      disease in head and neck. CT and clinicopathological data of 12 patients with
      Kimura disease diagnosed between May 2011 and May 2015 were analyzed. The mean
      age was 43.9 years and the disease course varied from 1 week-20 years. The mean
      absolute value of eosinophil granulocytes was 1.95*109/l. Multiple nodules were
      detected in 4 patients with Kimura disease. Main symptoms included multiple
      enlarged lymph nodes in neck and submaxillary regions. CT imaging of nodular
      lesions revealed a clear boundary, with moderate to marked homogeneous
      enhancement. Diffuse mass lesions were observed in 6 patients with Kimura
      disease. Main symptoms included subcutaneous diffuse soft tissue mass in parotid
      gland and maxillofacial regions. CT imaging of diffuse mass revealed unclear
      boundaries, adjacent skin thickness and moderate heterogeneous enhancement. In
      some cases, the diffuse mass involved soft mass with unclear boundaries.
      Pathological symptoms of Kimura disease included infiltration of eosinophilia,
      lymphocytic proliferation, formation of lymphatic follicles and variable degrees
      of fibrosis and vascular proliferation. Diagnosis of Kimura disease in head and
      neck regions may be improved based on lesions with clear or unclear boundaries,
      homogeneous or heterogeneous enhancement, with or without lymphadenectasis and by
      the presence of peripheral blood eosinophilia. However, a final diagnosis relies
      on a pathological examination.

PMID- 30186445
TI  - Combination of catheter ablation for non-valvular atrial fibrillation and left
      atrial appendage occlusion in a single procedure.
AB  - Patients with atrial fibrillation (AF) have an increased risk of stroke and
      systemic embolism. Catheter ablation (CA) is increasingly applied for the
      treatment for drug-refractory AF; however, its long-term success rate is <50%. It
      has been proved that percutaneous left atrial appendage occlusion (LAAO) exerts
      the same efficacy as novel oral anti-coagulants [(N)OACs] in reducing
      thromboembolic events. The present study investigated whether a combined
      procedure of AF ablation and LAAO may be feasible and efficacious. CA was
      performed for patients with AF and a high risk of stroke according to their
      CHADS2 or CHA2DS2-VASc score, and LAAO was performed using the Watchman device. A
      total of 25 patients (40% females; mean age, 64.2+/-3.5 years) who were treated
      between July 2016 and June 2017 were included in the present study. The median
      CHA2DS2-VASc score was 4.5 (range, 2-6) and the median HAS-BLED score was 3.17
      (range, 1-7). Successful CA and LAAO were performed in 100% of cases. All
      patients met the criteria for successful LAAO. At the 6-month follow-up, complete
      sealing of the LAA was achieved in 23 patients (92%), while a minimal residual
      flow (<5 mm) was detected in 2 patients (8%). In 24 patients (96%), the
      administration of (N)OACs was terminated and aspirin administration was initiated
      at the 6-month follow-up. (N)OAC treatment was maintained in 1 patient (4%) on
      the basis of transient ischemic attack. During the 6-month follow-up period, 3
      patients who had a recurrence of AF received a repeated ablation. In conclusion,
      the combination of CA and LAAO in a single procedure is feasible, safe and
      efficacious for patients with non-valvular AF at a high risk of stroke, and a
      contraindication regarding the use of (N)OACs.

PMID- 30186446
TI  - Wnt3a-regulated TCF4/beta-catenin complex directly activates the key Hedgehog
      signalling genes Smo and Gli1.
AB  - The Wnt and Hedgehog signalling pathways serve key roles in diverse developmental
      processes. However, the molecular associations between these two signalling
      pathways remains unclear. Previous transcriptome studies on human foreskin
      fibroblasts have indicated that Wnt signalling activation induces the expression
      of key Hedgehog signalling genes, including smoothened, frizzled class receptor
      (Smo) and GLI family zinc finger 1 (Gli1). Reverse transcription-quantitative
      polymerase chain reaction (RT-qPCR) results revealed that Wnt3a treatment induced
      the expression of the key Hedgehog signalling genes, including Smo, patched
      (PTCH), Gli1, Gli2 and Gli3. In addition, western blot analyses demonstrated that
      Wnt3a treatment resulted in the accumulation of cellular Smo and Gli proteins.
      Furthermore, promoter sequence analysis revealed that the putative beta-catenin/T
      cell factor (TCF)-4 complex binding motifs (T/AC/GAAAG) were located within 1.5
      kb of the Smo and Gli1 promoters. Results of the chromatin immunoprecipitation
      experiments and yeast-one hybrid assays revealed that TCF4 directly binds to the
      Smo and Gli1 promoters, with two binding sites for Smo and a single binding site
      for Gli1. Further analysis showed that the beta-catenin/TCF4 complex binds to the
      Smo and Gli1 promoters. To investigate the functions of TCF4 and beta-catenin in
      transcriptional regulation of Smo and Gli1, TCF4 and beta-catenin were
      transiently expressed in fibroblast cells. RT-qPCR results demonstrated that
      overexpression of TCF4 and beta-catenin induced the expression of Smo and Gli1.
      In addition, small interfering RNA-mediated suppression of beta-catenin resulted
      in the downregulation of Smo and Gli1 expression levels, even under Wnt3a
      treatment. Suppression of beta-catenin and Gli1 expression inhibited cell
      proliferation. Taken together, the results of the present study suggested that
      the beta-catenin/TCF4 complex directly activates Smo and Gli1 by binding to their
      promoters, which in turn controls cell proliferation in human fibroblasts.

PMID- 30186447
TI  - Preliminary study on the effect of brazilin on biofilms of Staphylococcus aureus.
AB  - Biofilms significantly enhance antibiotic resistance by inhibiting penetration of
      antibiotics and are shielded from the immune system via the formation of an
      extracellular polymeric matrix. Innovative and novel approaches are required for
      the inhibition of biofilm formation and treatment of biofilm-associated
      infectious diseases. In the current study, a biofilm model of Staphylococcus
      aureus was established in vitro to explore inhibitory effects of brazilin (BN) on
      biofilm formation and to evaluate damaging effects of BN in the presence and
      absence of vancomycin (VCM) on the biofilm. Antibiofilm-infection mechanisms of
      BN were observed. In these experiments, the clinical strain of S. aureus C-4-4
      was isolated for biofilm formation. Crystal violet staining and fluorescence
      microscopy revealed that BN inhibited biofilm formation in vitro and the best
      effect was observed with two times the minimum inhibitory concentration of BN
      following 48 h incubation. Additionally, the results demonstrated that BN in
      combination with VCM enhanced the damage to biofilms, whereas VCM alone did not.
      The results of the reverse transcription-quantitative polymerase chain reaction
      analyses demonstrated that BN downregulated gene expression of intercellular
      adhesion (ica)A and upregulated icaR and the quorum-sensing (QS) system regulator
      accessory gene regulator A. In summary, BN inhibited S. aureus biofilm formation
      and destroyed biofilms, while simultaneously increasing permeability to VCM. BN
      was able to reduce production of the extracellular polymeric matrix and inhibited
      the QS system. These results support the use of BN as a novel drug and treatment
      strategy for S. aureus biofilm-associated infections.

PMID- 30186448
TI  - Clinical therapy of hyaluronic acid combined with platelet-rich plasma for the
      treatment of knee osteoarthritis.
AB  - Knee osteoarthritis is the most common degenerative disease of the joints caused
      by articular cartilage injury, degradation of the joint edge and subchondral bone
      hyperplasia. Various treatments are used to alleviate the symptoms of patients
      with knee osteoarthritis, including analgesics and intra-articular injections.
      Platelet-rich plasma (PRP) is an autologous and multifunctional platelet
      concentrate of the blood, which stimulates the cartilage healing process and
      improves the damage caused by articular disease. Hyaluronic acid (HA) is an
      effective treatment for patients with knee osteoarthritis. In the current study,
      the effectiveness of PRP and HA combination therapy administered via intra
      articular injections for patients with knee osteoarthritis was analyzed. A total
      of 360 patients with knee osteoarthritis were randomized into four different
      treatment groups as follows: Double-blind treatment with PRP (2-14 ml); double
      blind treatment with HA (0.1-0.3 mg); combination therapy of PRP and HA; and
      placebo groups. Following treatment, all patients were evaluated using the
      Western Ontario and McMaster Universities Arthritis Index (WOMAC) and Common
      Toxicity Criteria. The most common treatment-emergent adverse events were
      hypertension and proteinuria. The current study demonstrated that PRP and HA
      treatment significantly improved arthralgia, and PRP treatment was determined to
      be significantly more effective than HA treatment using the WOMAC pain score
      (P<0.05). PRP and HA combination treatment significantly improved arthralgia,
      reduced humoral and cellular immune responses and promoted angiogenesis, which
      improved the patients' histological parameters compared with PRP or HA treatment
      alone. These results suggested that PRP and HA combination treatment may be a
      potential treatment option for patients with knee osteoarthritis in the future.

PMID- 30186449
TI  - Inflammatory cytokine expression in patients with sepsis at an intensive care
      unit.
AB  - Sepsis is a systemic inflammatory response syndrome caused by infection of
      bacteria, fungi and/or viruses in clinical patients. It is known that
      inflammatory cytokine levels have an essential role in the progression of sepsis.
      The present study investigated the role of inflammatory markers in human
      peripheral blood mononuclear cells (hPBMCs) of patients with sepsis at an
      intensive care unit. In addition, the plasma levels of inflammatory cytokines
      were compared between sepsis patients and healthy individuals. The results
      demonstrated that the serum levels of interleukin-1, -17 and -6, as well as tumor
      necrosis factor-alpha, were upregulated in sepsis patients. The serum levels of
      high mobility group box 1 and C-reactive protein were increased in sepsis
      patients compared with those in healthy individuals. The expression levels of
      nuclear factor-kappaB-p65 and its inhibitor IkappaBalpha, as well as the ratio of
      CD25+ cells, and the levels of neutrophil gelatinase-associated lipocalin and
      peptidoglycan recognition protein were higher in hPBMCs in sepsis patients
      compared with those in healthy individuals. It was also indicated that balance of
      T helper type 1/2 cytokines was also disturbed in patients with sepsis compared
      with that in healthy individuals. In conclusion, these results indicated that
      inflammation is involved in the progression of sepsis by interfering with the
      expression of various molecules, suggesting a potential therapeutic strategy for
      the treatment of sepsis patients.

PMID- 30186450
TI  - The 4-hydroxynonenal mediated oxidative damage of blood proteins and lipids
      involves secondary lipid peroxidation reactions.
AB  - Lipid peroxidation is associated with several metabolic diseases. Lipid
      peroxidation causes cellular damage through reactive aldehyde species such as 4
      hydroxyonenal (4-HNE). The exact mechanism(s) by which 4-HNE causes damage in the
      intravascular compartment is not yet exactly understood. Using an in vitro
      system, the damage induced by 4-HNE on the blood was investigated by measuring
      protein carbonyl groups and thiobarbituric acid reactive substances (TBARS)
      following 4-HNE treatment. The findings demonstrated that treatment with 4-HNE
      increased the carbonylation of protein and the formation of TBARS in the blood
      plasma. It was also tested whether phenelzine, a scavenger of aldehyde species,
      or U-83836E, a scavenger of lipid peroxy radicals, attenuated the damage caused
      by 4-HNE. It was demonstrated that phenelzine or U-83836E both mitigated the
      effects of 4-HNE on the proteins and the lipids of the blood plasma. The findings
      of the current study suggest that phenelzine, U-83836E or functionally similar
      therapeutics may prevent or treat diseases that involve an increased production
      of 4-HNE in the intravascular compartment.

PMID- 30186451
TI  - Andrographolide attenuates viral myocarditis through interactions with the IL
      10/STAT3 and P13K/AKT/NF-kappabeta signaling pathways.
AB  - As a cardiac disease caused by the inflammation of the heart muscle, viral
      myocarditis (VMC) causes dilated cardiomyopathy, congestive heart failure and
      even death. With anti-inflammatory activities, andrographolide has been used in
      the treatment of various human diseases. In the present study, therapeutic
      effects of andrographolide on VMC were investigated using a VMC mouse model.
      Measurement of physiological indexes and echocardiographic examination was
      performed to explore the effects of andrographolide on cardiac function in mice
      with VMC. Levels of TNF-alpha, hs-CRP and cTnl in serum were measured by enzyme
      linked immunosorbent assay (ELISA). Effects of andrographolide on the expression
      of L-10, STAT3, NF-kappabeta p65 and NF-kappabeta p50 were investigated by
      western blot analysis. Results indicated that andrographolide treatment reduced
      serum levels of TNF-alpha, hs-CRP and cTnl, increased the expression levels of IL
      10 and STAT3 and reduced the expression levels of NF-kappabeta p65 and NF
      kappabeta p50 and the phosphorylation levels of phosphoinositide 3-kinase (P13K)
      and AKT in the heart tissues of mice with VMC. In addition, andrographolide also
      increased the expression level of Ikappabetaalpha in heart tissue. Therefore, it
      was concluded that andrographolide may inhibit the progression of VMC by
      interacting with the IL-10/STAT3 and NF-kappabeta signaling pathways.

PMID- 30186452
TI  - Transanal endorectal stepwise gradient muscular cuff cutting pull-through method:
      Technique refinements and comparison with laparoscopy-assisted procedures.
AB  - In all existing radical resection procedures available for Hirschprung's disease
      (HD), the muscular cuff has been retained. In recent years, our study group has
      modified the procedure using a stepwise gradient muscular cuff cutting pull
      through method for the treatment of HD. The objective of the present study was to
      assess patient prognosis following the use of the transanal endorectal pull
      through (TEPT) method or the laparoscopy-assisted pull-through (LPT) method and
      to provide evidence to assist in clinical decisions. The medical records of 172
      patients (age, >=3 years) who underwent TEPT or LPT for HD between September 2003
      and August 2014 at the Pediatric Surgery Department of The Affiliated Hospital of
      Zunyi Medical College (Zunyi, China) were reviewed (TEPT, n=94; LPT, n=78).
      Preoperative, intraoperative and post-operative data for the subjects involved
      were recorded. Each patient's family was interviewed using a uniform 12-item post
      pull-through long-term outcome questionnaire, which was scored in order to
      compare the short and long-term treatment outcomes of patients in each group.
      Patients in the LPT group had significantly prolonged operating times, reduced
      intraoperative blood loss and perioperative transfusion rates and shorter anal
      dissection times. Furthermore, the oral feeding time and length of hospital stay
      were similar between groups. There were no significant differences in early
      complications between the groups. No significant differences in late
      complications, including anastomotic stricture and enterocolitis were observed;
      however, the soiling and constipation rates were significantly higher in the TEPT
      group compared with the LPT group. The stool pattern score was not significantly
      different between groups, while the frequency of bowel movements in the LPT group
      was significantly higher compared with the TEPT group from 9-24 months post
      surgery. The stepwise gradient muscular cuff cutting pull-through method
      demonstrated a good safety profile and efficacy with regard to the long-term
      outcomes of patients with HD. These results support the clinical application of
      LPT as a promising surgical approach for children with HD.

PMID- 30186453
TI  - Reversible splenial lesion syndrome associated with acute Mycoplasma pneumoniae
      associated encephalitis: A report of four cases and literature review.
AB  - Reversible splenial lesion syndrome (RESLES) is a rare clinico-radiological
      syndrome that is defined as reversible lesions that involve the splenium of the
      corpus callosum (SCC). RESLES has been reported in patients with a broad spectrum
      of diseases and conditions, including infections, hypoglycemia and poisoning. The
      present report described four RESLES cases triggered by Mycoplasma pneumoniae (M.
      pneumoniae) and discussed the associated diagnostic challenges. Four cases of
      acute M. pneumoniae-associated encephalitis that displayed RESLES were reviewed.
      The clinical presentations were nonspecific in these patients. However, magnetic
      resonance imaging (MRI) revealed consistent lesions in the SCC with a
      hyperintensity in diffusion-weighted imaging (DWI) and hypointensities in T1WI,
      which disappeared after a variable lapse. Treatment with azithromycin or combined
      treatment with immunomodulatory agents if necessary led to a good prognosis. The
      present findings indicated that radiological diagnosis of RESLES should be
      considered in patients with M. pneumoniae-associated encephalitis. Furthermore,
      serum Mycoplasma antibody is important for the diagnosis of M. pneumoniae
      associated encephalitis.

PMID- 30186455
TI  - Erratum: Tanshinone IIA and Astragaloside IV promote the angiogenesis of
      mesenchymal stem cell-derived endothelial cell-like cells via upregulation of
      Cx37, Cx40 and Cx43.
AB  - [This corrects the article DOI: 10.3892/etm.2017.5636.].

PMID- 30186454
TI  - Antitumor effect of recombinant Mycobacterium smegmatis expressing MAGEA3 and
      SSX2 fusion proteins.
AB  - Mycobacterium smegmatis (M. smegmatis), which is a nonpathogenic and fast-growing
      mycobacterium, is a potential vaccine vector capable of expressing heterologous
      antigens. Spontaneous humoral and cellular immune responses have been
      demonstrated against cancer/testis antigens (CTA), including melanoma-associated
      antigen A (MAGEA) and SSX. In the present study, recombinant plasmids expressing
      MAGEA3 and SSX2 were constructed. The recombinant plasmids were transferred into
      M. smegmatis to generate the novel antitumor DNA vaccine. As MAGEA3 and SSX2 were
      in different ligation sequences, the two DNA vaccines were recombinant M.
      smegmatis MAGEA3-SSX2 (rM.S-MS) and recombinant M. smegmatis SSX2-MAGEA3 (rM.S
      SM), respectively. The expression levels of Fusion proteins were assessed by
      western blotting. BALB/c mice were immunized with rM.S and western blot analysis
      was used to determine whether antibodies against MAGEA3 or SSX2 were produced in
      immunized mice. EC9706 cells were inoculated into BALB/c nude mice and the mice
      were maintained until an obvious visible tumor appeared on the back.
      Subsequently, the blood from the rM.S immunized BALB/c mice was injected into the
      BALB/c nude mice via the tail vein. In order to evaluate the antitumor effect of
      the vaccines, tumor volume and weight were measured 5 to 21 days after injection.
      Mice were euthanized on day 21 of tumor growth, and the tumor was dissected and
      weighed. The two fusion proteins were expressed in the rM.S and the specific
      fusion protein antibodies were expressed in the blood of immunized BALB/c mice.
      The tumor volumes and weight in the recombinant M. smegmatis MAGEA3 (rM.S-M) and
      recombinant M. smegmatis SSX2 (rM.S-S) groups were significantly reduced compared
      with the control group. Furthermore, the decrease in tumor volumes and weight in
      the rM.S-MS and rM.S-SM groups was more severe than in the rM.S-M or rM.S-S
      groups. There was no significant difference in the antitumor effect of the rM.S
      MS and rM.S-SM groups. The present findings suggest that this rM.S may be a
      potential candidate therapeutic vaccine for the treatment of cancer.

PMID- 30186456
TI  - Cycloastragenol: An exciting novel candidate for age-associated diseases.
AB  - Cycloastragenol (CAG) is a triterpenoid saponin compound and a hydrolysis product
      of the main active ingredient in Astragalus membranaceus (Fisch.) Bunge. An
      increasing body of evidence has indicated that CAG has a wide spectrum of
      pharmacological functions, which are attracting attention in the research
      community. The aim of the present review paper was to review and elucidate the
      advanced study of CAG. The focus was on advanced studies of CAG in English and
      Chinese databases; the literature was collected and reviewed to summarize the
      latest efficacy, pharmacokinetics and adverse reactions of CAG. Extensive
      pharmacological effects have been attributed to CAG, including telomerase
      activation, telomere elongation, anti-inflammatory and anti-oxidative properties;
      CAG has also been reported to improve lipid metabolism. Clinical research has
      demonstrated that CAG activates telomerase in humans and ameliorates various
      biomarkers. CAG is absorbed through the intestinal epithelium via passive
      diffusion and undergoes first-pass hepatic metabolism. Within a certain dose
      range, oral CAG is relatively safe; however, underlying mechanisms associated
      with CAG are not clear, and thus, we should be aware of potential adverse
      reactions associated with CAG. According to existing studies and clinical trials,
      CAG is safe and has broad application prospects. However, further studies are
      required to fully understand its efficacy and potential adverse reactions, and to
      ensure the proper use of CAG is applied to treat diseases clinically.

PMID- 30186458
TI  - Effect of hyperbaric oxygenation therapy on post-concussion syndrome.
AB  - The present review evaluated the effect of hyperbaric oxygenation (HBO) therapy
      on post-concussion syndrome (PCS). Searches for publications from the earliest
      date possible up until the first week of 2016 were conducted using the electronic
      databases Cochrane, EBSCOhost, Embase, Ovid MEDLINE, PubMed and Web of Science.
      Additional trials were identified through reference list scanning. Randomized
      controlled trials assessing the effectiveness of HBO therapy in PCS were selected
      and tested for eligibility for inclusion in the present review. Two independent
      reviewers conducted data extraction and the Cochrane Collaboration's recommended
      method was used to assess the risk of bias in each study included. Review Manager
      5.3 software was used for data synthesis and analysis and the standardized mean
      difference (SMD) or mean difference (MD) was estimated with a fixed or random
      effects model using a 95% confidence interval (CI). A total of 127 articles were
      identified, 4 of which were eligible for final analysis. The meta-analysis
      identified no difference in the Rivermead Post-Concussion Symptoms Questionnaire
      (MD=1.23; 95% CI, -3.47-5.94; P>0.05; I2=35%) or Post-Traumatic Stress Disorder
      Checklist (PCL) scores (SMD=0.12; 95% CI, -0.31-0.54; P>0.05; I2=0%) scores
      between groups receiving different oxygen doses. The differences in PCL scores
      (SMD=-0.13, 95% CI, -0.80-0.53; P>0.05; I2=63%) and neurobehavioral symptoms
      (SMD=-1.00, 95% CI, -2.58-0.58; P>0.05; I2=92%) between the HBO and sham groups
      were not significant. The current study demonstrated that HBO therapy has no
      significant effect on PCS compared with the sham group. Therefore, it was
      determined that effective design and execution of a large clinical trial, which
      includes treatment, control and sham groups is required in the future.

PMID- 30186459
TI  - Applications and development of permeability imaging in ischemic stroke.
AB  - Brain permeability imaging techniques are specific for the assessment of blood
      brain barrier integrity. The present review article primarily focuses on the
      application of permeability imaging in cases of ischemic stroke. The permeability
      maps may be used to predict future hemorrhagic transformation in patients
      following acute ischemic stroke, that have been treated with tissue plasminogen
      activator (tPA) or recanalization therapy. The permeability imaging would help
      make the clinical decision to administer tPA following acute ischemic stroke or
      not, which is not only due to the current 3-4.5 h time window. Additionally,
      permeability imaging may also be used to evaluate the collateral circulation in
      the perfusion and permeability of the ischemic area of the brain.

PMID- 30186457
TI  - Novel treatment strategies for patients with HER2-positive breast cancer who do
      not benefit from current targeted therapy drugs.
AB  - Human epidermal growth factor receptor-2 positive breast cancer (HER2+ BC) is
      characterized by a high rate of metastasis and drug resistance. The advent of
      targeted therapy drugs greatly improves the prognosis of HER2+ BC patients.
      However, drug resistance or severe side effects have limited the application of
      targeted therapy drugs. To achieve more effective treatment, considerable
      research has concentrated on strategies to overcome drug resistance. Abemaciclib
      (CDK4/6 inhibitor), a new antibody-drug conjugate (ADC), src homology 2 (SH2)
      containing tyrosine phosphatase-1 (SHP-1) and fatty acid synthase (FASN) have
      been demonstrated to improve drug resistance. In addition, using an effective
      vector to accurately deliver drugs to tumors has shown good application
      prospects. Many studies have also found that natural anti-cancer substances
      produced effective results during in vitro and in vivo anti-HER2+ BC research.
      This review aimed to summarize the current status of potential clinical drugs
      that may benefit HER2+ BC patients in the future.

PMID- 30186460
TI  - In vitro study on human umbilical cord mesenchymal stem cells transfected with
      lentivirus-mediated hNIS-EGFP dual reporter gene and co-labeled with
      superparamagnetic iron oxide.
AB  - The aim of the present study was to establish a stem cell line for multi-mode
      imaging (in vivo fluorescence imaging, magnetic resonance imaging and 99mTc
      single-photon emission computed tomography) and to study the biological activity,
      stemness, proliferative activity and differentiation ability of superparamagnetic
      iron oxide (SPIO), human sodium/iodide symporter (hNIS) and enhanced green
      fluorescent protein (EGFP) co-labeled human umbilical cord mesenchymal stem cells
      (hUCMSCs). The EGFP reporter gene was selected to indirectly reflect the
      expression of target gene hNIS, and hUCMSCs were re-transfected with the
      successfully constructed recombinant plasmid pCMV-NIS-EF1-GFP-PGK-puro. When a
      stem cell line stably expressing hNIS and EGFP was obtained, the cells were
      incubated with 30 ug/ml SPIO to obtain hNIS, EGFP and SPIO co-labeled stem cells.
      The protein expressions of hNIS and EGFP were identified using western blot
      analysis, and the protein function of hNIS was identified by 125I influx and 125I
      efflux experiments. hNIS-EGFP-hUCMSCs were labeled with SPIO under the mediation
      of poly-L-lysine, and SPIO, hNIS and EGFP co-labeled hUCMSCs were established
      successfully. Staining with Prussian blue confirmed that 98% of cells were
      successfully labeled with SPIO. Western blotting results demonstrated positive
      hNIS and EGFP protein expression levels, and 125I influx and 125I efflux
      experiments confirmed that the protein function of hUCMSCs after expressing hNIS
      was normal. The uptake of 125I was higher in cell lines hNIS-EGFP-hUCMSCs than in
      control hUCMSCs (fold change: 16.43+/-2.30 times; P<0.05). The stemness of hNIS
      EGFP-hUCMSCs was found to be slightly decreased but not statistically
      significant; the overall characteristics of stem cells remained unchanged. The
      assessments of adipogenic and osteogenic differentiation suggest that hNIS-EGFP
      hUCMSCs have no significantly different characteristics compared with primary
      hUCMSCs.

PMID- 30186461
TI  - Protective effects of primary neural stem cell treatment in ischemic stroke
      models.
AB  - Strokes are a major cause of neurological disability. Stem cell replacement
      therapy is a potential novel strategy of treating patients that have experienced
      strokes. The present study examined the protective role of neural stem cell (NSC)
      administration in oxygen-glucose deprivation (OGD) injury and ischemic stroke
      animal models. Primary cultured embryonic NSCs and brain microvascular
      endothelial cells were indirectly co-cultured for in vitro testing. A rat model
      of embolic middle cerebral artery occlusion (MCAO) was used to assess the
      morphological and functional changes that occur following treatment with NSCs.
      The role of the phosphoinositide 3-kinase/protein kinase b/glycogen synthase
      kinase 3beta (PI3K/Akt/GSK-3beta) signaling pathway in the neuroprotective
      effects of NSC treatment was also determined. It was demonstrated in vivo and in
      vitro that NSC administration may attenuate the brain injury caused by stroke.
      Furthermore, the results suggest that activation of PI3k/Akt/GSK-3beta signaling
      pathway serves a role in attenuating OGD injury. Inflammation, synaptic
      remodeling and autophagy may be improved following NSC treatment and behavioral
      testing suggests that treatment with NSCs improves functional recovery in rats
      following MCAO.

PMID- 30186462
TI  - Morroniside protects against cerebral ischemia/reperfusion injury by inhibiting
      neuron apoptosis and MMP2/9 expression.
AB  - The aim of the present study was to investigate the effect of morroniside against
      matrix metalloproteinase (MMP)2/9 and focal cerebral ischemia/reperfusion (I/R)
      injury in rats. A rat model of focal cerebral I/R injury rats was established and
      rats were administered with 30, 90 or 270 mg/kg/day morroniside for 7 days. The
      expression of MMP2/9 and neuronal apoptosis were assessed. In addition, the
      expression of active caspase-3, B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X
      protein (Bax) were measured. The results revealed that MMP2 and MMP9 expression
      was upregulated and the percentage of apoptotic neurons was increased in rats
      with focal cerebral I/R injury compared with the control. However, treatment with
      morroniside significantly inhibited I/R-induced MMP2/9 expression and neuron
      apoptosis compared with the untreated I/R injury group. Morroniside
      administration also decreased the expression of active caspase-3 and increased
      the Bcl-2/Bax ratio compared with untreated rats with focal cerebral I/R injury.
      The inhibitory effect of morroniside on MMP2/9 expression and neuron apoptosis
      was dose dependent. In summary, the results of the present study suggest that
      morroniside is able to protect against cerebral I/R injury in the brain and may
      have potential as a therapeutic treatment for patients who have suffered a
      stroke.

PMID- 30186464
TI  - Long non-coding RNA NEAT1 promotes migration and invasion of oral squamous cell
      carcinoma cells by sponging microRNA-365.
AB  - Long non-coding RNA nuclear enriched abundant transcript 1 (NEAT1) has been
      demonstrated to serve key roles in numerous human cancer types, but its function
      in oral squamous cell carcinoma (OSCC) and underlying regulatory mechanism have
      not been evaluated. The present study demonstrated that expression of NEAT1 was
      significantly higher in OSCC tissue and cell lines compared with adjacent non
      tumour tissue and normal oral keratinocytes, respectively. Additionally,
      upregulation of NEAT1 was significantly associated with advanced clinical stage
      and shorter survival time in patients with OSCC. Bioinformatics analysis and
      luciferase reporter gene assay data confirmed the interaction between NEAT1 and
      miR-365, and it was revealed that NEAT1 may downregulate microRNA (miR)-365
      expression in OSCC cells. Furthermore, inhibition of NEAT1 expression led to a
      significant reduction in OSCC cell migration and invasion, which was accompanied
      by reduced matrix metalloproteinase (MMP)-2 and MMP9 protein expression. By
      contrast, inhibition of miR-365 eliminated suppressive effects of NEAT1 knockdown
      on OSCC cell migration and invasion. miR-365 was significantly downregulated in
      OSCC tissue and cell lines and an inverse correlation between miR-365 and NEAT1
      expression in OSCC tissue was observed. To conclude, the present study
      demonstrated that NEAT1 promoted migration and invasiveness of OSCC cells by
      sponging miR-365. The current study suggests that NEAT1 may serve as a novel
      therapeutic target for the treatment of OSCC.

PMID- 30186463
TI  - Long noncoding RNA EZR-AS1 promotes tumor growth and metastasis by modulating
      Wnt/beta-catenin pathway in breast cancer.
AB  - Accumulating evidence has demonstrated that long noncoding RNAs (lncRNAs) serve
      important roles in tumor development and progression. However, whether lncRNA EZR
      AS1 is associated with breast cancer (BC) progression remains unclear. In the
      present study, reverse transcription-quantitative polymerase chain reaction
      analysis demonstrated that the expression of EZR-AS1 was significantly
      upregulated in BC tissues and cell lines. Furthermore, Kaplan-Meier curve
      analysis revealed that increased EZR-AS1 expression in patients with BC
      contributes to poor prognosis. Cell counting kit-8 and fluorescence-activated
      cell sorting experiments indicated that EZR-AS1 knockdown significantly
      suppressed the proliferation and cell cycle progression of breast cancer cells,
      while reducing cellular apoptosis. Furthermore, Transwell assays suggested that
      EZR-AS1 knockdown reduced the migration and invasion ability of BC cells compared
      with control cells. In the present study, it was observed that EZR-AS1 interacts
      with beta-catenin to prevent degradation. EZR-AS1 knockdown resulted in beta
      catenin downregulation and inactivation of the Wnt/beta-catenin pathway. Rescue
      assays revealed that beta-catenin overexpression reversed the effects of EZR-AS1
      knockdown on BC cell proliferation, apoptosis, migration and invasion. In
      conclusion, the results of the present study demonstrate that EZR-AS1 serves as
      an oncogene in BC via activating the Wnt/beta-catenin pathway. This suggests that
      EZR-AS1 may be a therapeutic target for BC treatment.

PMID- 30186465
TI  - Free bladder mucosa graft harvested by water-jet: A novel, minimally invasive
      technique for urethral reconstruction.
AB  - The aim of the current study was to describe a novel approach of urethral
      reconstruction through minimally invasive harvesting of the bladder graft via
      endoscopic sub-mucosal dissection of water-jet. The records of two patients were
      reviewed, who underwent transurethral endoscopic surgical bladder mucosa graft
      harvest by water-jet and urethral reconstruction with informed consent. Case 1
      was a 35-year-old male with anterior urethral stricture; case 2 was a 22-year-old
      male with secondary anterior urethral stricture and hypospadias following a
      failed hypospadias surgery. The two male patients successfully underwent urethral
      reconstruction using bladder mucosa graft harvested via endoscopic assisted by
      water-jet; no perforation, cysthemorrhagia or any other postoperative bladder
      related complication was observed. Voiding cystourethrogram of case 1 indicated
      that the reconstructed urethra was unobstructed, and no recrudescence was
      observed within 4 months of follow-up. In case 2, dysuria had disappeared
      completely within 1 month of follow-up, and the urethra plate was successfully
      reconstructed by first-stage. To the best of our knowledge, this is the first
      report to demonstrate urethral reconstruction using a bladder mucosa graft
      harvested by transurethral endoscopic sub-mucosal dissection, assisted by water
      jet. Transurethral endoscopic surgery may provide a minimally invasive approach
      instead of the traditional open surgery for harvesting bladder mucosa graft.
      Urethral reconstruction conducted with bladder mucosa graft harvested via
      endoscopic sub-mucosal dissection assisted by water-jet is a feasible and safe
      method, and the short-term follow-up results are encouraging.

PMID- 30186466
TI  - Thromboelastography-derived parameters for the prediction of acute
      thromboembolism following non-steroidal anti-inflammatory drug-induced
      gastrointestinal bleeding: A retrospective study.
AB  - Efficacy of thromboelastography (TEG)-derived parameters for the prediction of
      acute thromboembolism (AT) in patients with non-steroidal anti-inflammatory drug
      (NSAID)-induced gastrointestinal bleeding (GIB) remains to be determined. A
      retrospective propensity score matching (PSM) study was performed to evaluate
      this efficacy. Patients with NSAID-induced GIB (98 with AT; 830 without AT) were
      matched for age, sex and history of cardiovascular and cerebrovascular diseases
      using PSM. Multivariate logistic regression was used to determine the efficacy of
      TEG-derived predictors of AT. Mean Decrease Gini (MDG) coefficients were used to
      rank the importance of the variables from random forest algorithm results.
      Univariate analysis indicated that the following indexes were significantly
      different between the two groups: Reaction time (R value), coagulation forming
      time, solidification angle, maximum amplitude (MA), coagulation index (CI),
      hemoglobin levels, D-dimer levels, platelet aggregation test (pAgt) results,
      fibrinogen levels and Acute Physiology and Chronic Health Evaluation II score
      (all P<0.001). Multifactor logistic regression analysis indicated that the R
      value (P=0.010), solidification angle (P=0.004), MA (P=0.038), D-dimer levels
      (P=0.012) and pAgt results (P=0.015) were independent predictors of AT in
      patients with NSAID-induced GIB, achieving an area under the curve of 0.999 in
      receiver operating characteristic curve analyses. The five most important
      parameters according to the MDG scores (MDGS) were: Solidification angle
      (MDGS=58.14), R value (MDGS=20.42), pAgt results (MDGS=15.61), D-dimer levels
      (MDGS=12.78) and CI (MDGS=12.61). The results of the present study indicated that
      TEG-derived parameters including the R value, solidification angle, MA and CI, as
      well as D-dimer levels and pAgt score were significant predictors of AT in
      patients with NSAID-induced GIB.

PMID- 30186467
TI  - Hes1 negatively regulates neurogenesis in the adult mouse dentate gyrus following
      traumatic brain injury.
AB  - Traumatic brain injury (TBI) results in the activation of neurogenesis, but it
      also triggers multiple cell signaling pathways that may lead to either cell
      damage or cell survival. In general, the repair processes following TBI are
      characterized by a failure to replenish the neuronal population entirely. To
      date, the factors that determine whether neurogenesis will be sufficient for the
      replacement of lost neurons following brain injury are not fully understood.
      Decreased activation of Hes1, a transcriptional repressor, is observed as neural
      differentiation proceeds, and this gene continues to play a role in the
      quiescence of stem cells into adulthood. Since Hes1 is negatively correlated with
      neurogenesis in adult rodents, the present study investigated whether this gene
      inhibits TBI-induced neurogenesis by use of adenovirus-mediated gene transfer to
      upregulate Hes1 expression in the dentate gyrus (DG) in a mouse model of TBI.
      Western blot analysis and immunofluorescent staining revealed increased Hes1
      protein expression in the subgranular zone (SGZ) of the DG following adenovirus
      Hes1 (Ad-Hes1) transfection and a decreased number of bromodeoxyuridine-positive
      and doublecortin-positive cells in the SGZ in the transfection group following
      TBI. These data indicated a negative association between the expression of Hes1
      and adult neurogenesis following the induction of TBI. Furthermore, the present
      findings demonstrate the value of downregulating Hes1 expression following TBI to
      promote the initiation of endogenous neurogenesis, which may be of therapeutic
      value for patients with brain injuries.

PMID- 30186468
TI  - Triptolide protects podocytes via autophagy in immunoglobulin A nephropathy.
AB  - Triptolide is often used to treat patients with immunoglobulin A nephropathy
      (IgAN), especially in Asia. However, its detailed mechanism remains unclear. In
      vitro experiments were conducted with podocytes exposed to aggregated IgA (aIgA)
      MSC1097-conditioned media. A total of four groups were compared in this study: A
      control group (CON); a healthy supernatant group (HEAs); an IgAN supernatant
      group (IgANs); and a triptolide group (TRI). First, aggregated IgA1 (aIgA1) was
      generated by heating monomeric IgA1 (mIgA1) from IgAN patients or healthy
      subjects. Next, the conditioned supernatant of MSC-1097 cells cultured with aIgA1
      (100 mg/l) from IgAN patients (IgANs) or healthy subjects (HEAs) or without aIgA1
      (CON) were harvested and used to incubate MPC5 cells. MPC5 cells in the TRI group
      were cultured with triptolide (10 ng/ml) and conditioned media from MSC-1097
      cells cultured with aIgA1 from IgAN patients. After 24 h of treatment, MPC5 cells
      were collected to measure autophagy-related protein levels, including microtubule
      associated protein light chain 3 (LC3), p62, cluster of differentiation (CD)63,
      phosphorylated-protein kinase B (Akt), Akt, p-mammalian target of rapamycin
      (mTOR), and mTOR, via western blotting, immunofluorescence or both, and to
      determine apoptosis by flow cytometry. All the results showed no difference
      between the CON and the HEAs. Compared to the CON and the HEAs, MPC5 cells in the
      IgANs group showed reduced autophagy, which was presented as decreased levels of
      LC3-II and CD63, as well as accumulation of p62, and an increased podocyte
      apoptosis rate. This was partly rescued by the addition of triptolide. Moreover,
      the p-mTOR/mTOR ratio increased in the IgANs group and decreased in the TRI
      group. Therefore, these results suggest that triptolide protects podocyte
      autophagy in IgAN patients.

PMID- 30186469
TI  - Osteogenic potential of cell spheroids composed of varying ratios of gingiva
      derived and bone marrow stem cells using concave microwells.
AB  - The aim of the current study was to evaluate cell viability and osteogenic
      differentiation potential in cell spheroids composed of varying ratios of gingiva
      derived and bone marrow stem cells cultured in concave microwells. Cell spheroids
      were established from bone marrow and gingiva-derived stem cells in ratios of 6:0
      (Group 1), 2:1 (Group 2), 3:3 (Group 3), 1:2 (Group 4), and 0:6 (Group 5). On
      days 3 and 5, the viability of the cell spheroids was qualitatively analyzed
      using a calcein acetoxymethyl ester working solution and an ethidium homodimer-1
      live/dead assay. On days 1, 3, 5 and 7, a quantitative cell viability analysis
      was performed using a Cell Counting Kit-8. Alkaline phosphatase activity assays
      were performed using a commercially available kit on day 7 to assess osteogenic
      differentiation. In addition, reverse transcription-quantitative polymerase chain
      reaction and western blot analysis were performed to evaluate runt-related
      transcription factor 2 (Runx2) and osteocalcin expression. The ratio of gingiva
      derived to bone marrow stem cells did not affect the stem cell spheroid
      morphology. No significant changes in cell viability were noted among the
      different groups following incubation for 7 days. A consistent alkaline
      phosphatase activity was measured in co-cultured gingiva-derived and bone marrow
      stem cell spheroids of varying compositions. Runx2 and osteocalcin expression was
      increased when co-cultured compared with pure gingiva-derived or bone marrow stem
      cells. In conclusion, stem cell spheroids established by co-culturing maintained
      morphology, viability and a high osteogenic differentiation potential during the
      experimental period of 7 days. These spheroids containing human gingiva-derived
      and bone marrow stem cells may enhance the osteogenic differentiation potential.
      The use of multicell spheroids may be a simple and effective strategy for
      improving stem cell therapy.

PMID- 30186470
TI  - Research on the changes in balance motion behavior and learning, as well as
      memory abilities of rats with multiple cerebral concussion-induced chronic
      traumatic encephalopathy and the underlying mechanism.
AB  - To study the effects of multiple cerebral concussion (MCC)-induced chronic
      traumatic encephalopathy on balance motion behavior learning and memory abilities
      of rats and its possible mechanism. 4MCC rat models were established by means of
      striking the head (4MCC group, n=15), while normal Sprague-Dawley (SD) rats were
      used as controls (C group, n=15). At 2 weeks after injury, balance beam (BB)
      test, beam walking (BW) test and Morris water maze (MWM) test were performed,
      respectively. The metabolites in brain tissues of rats, the number of glial
      fibrillary acidic protein (GFAP)-positive cells and apoptotic cells in brain
      slices of rats, and the expression levels of phosphorylated tau (p-tau) and
      Abeta1-40 proteins were detected. The score of rats in 4MCC group was
      significantly lower than that in C group (p<0.01). The escape latencies of rats
      in 4MCC group on the 4th-7th days during training and the time reaching the
      platform were significantly longer (p<0.05), but the residence time in the target
      quadrant was obviously shorter (p<0.01). Naphthalene acetic acid (NAA) and
      creatinine (Cr) values in septal coronal section in 4MCC group were significantly
      lower, but choline (Cho) and myo-inositol (MI) values were obviously higher
      (p<0.01). The number of GFAP-positive cells in the hippocampal and septal areas
      in 4MCC group were significantly larger (p<0.01). In the hippocampal and septal
      areas of 4MCC group, the number of apoptotic cells was obviously larger (p<0.01),
      and the expression levels of p-tau and Abeta1-40 proteins were significantly
      higher (p<0.01). Thus, MCC-induced chronic traumatic encephalopathy can increase
      the expressions of p-tau and Abeta1-40 proteins in the hippocampal and septal
      areas, leading to damage of hippocampal and septal neurons and increasing the
      number of astrocytes in the hippocampal and septal areas, ultimately damaging the
      balance motion behavior and learning, as well as memory abilities of rats.

PMID- 30186471
TI  - Effects of glutamine on cytokines 1L-1 and TNF-alpha in rehabilitation and
      prognosis of patients with lobectomy.
AB  - This study was designed to investigate the effects of glutamine on cytokines 1L
      1, TNF-alpha and prognosis of patients with lobectomy in the process of
      postoperative rehabilitation. A total of 78 patients with lung cancer who
      underwent lobectomy from January 2015 to January 2017 were selected in Daqing
      Oilfield General Hospital (Daqing, China). Patients were randomly divided into
      two groups, 39 patients in each group. Patients in the control group were treated
      with conventional treatment, while patients in the observation group were treated
      with both conventional and glutamine treatment. The levels of TNF-alpha,
      endotoxin, serum IL-1, IL-10, IL-15, IL-18 and intercellular adhesion molecule-1
      (ICAM-1), myeloperoxidase (MPO) activity, incidence of nausea and vomiting,
      pulmonary histopathological changes, prognosis, and rehabilitation (time in bed,
      hospital stay and lung function) were compared between the two groups. Within 1
      year after treatment, most patients survived, except 2 patients in the
      observation group and 3 patients in the control group who died. The rate of
      postoperation infection in the observation group was slightly lower than that in
      the control group. After treatment, the levels of endotoxin and TNF-alpha in the
      observation group were significantly lower than those in the control group
      (p<0.05). After treatment, the serum levels of IL-1 and IL-10 were significantly
      higher and the serum levels of IL-15 and IL-18 were significantly lower in the
      observation group than those in the control group (p<0.05). The expression levels
      of ICAM-1 and MPO activity were significantly higher in the observation group
      than those in the control group (p<0.05). No significant difference in the
      incidence of nausea and vomiting was found between the two groups (p>0.05). The
      average postoperative bed rest and hospital stay in the observation group were
      significantly shorter than those in the control group (p<0.05). The levels of
      forced expiratory volume in 1 sec (FEV1), forced vital capacity (FVC) and peak
      expiratory flow rate (PEFR) in the observation group were significantly higher
      than those in the control group (p<0.05). The results indicated that glutamine
      treatment is effective in the postoperative rehabilitation of patients undergoing
      lobectomy. Glutamine can regulate the levels of IL-1 and TNF-alpha, improve lung
      function, shorten bed rest and hospitalization days, promote patients
      postoperative rehabilitation process, and improve patients quality of life.

PMID- 30186472
TI  - Effects of UV on apoptotic factors in lens epithelial cells of an animal model.
AB  - Effect of ultraviolet (UV) on the apoptotic factors p53, Bax and Bcl-2 in lens
      epithelial cells (LECs) was explored. Sixty SD rats were randomly divided into
      control group (n=12) and model group (n=48). Rats in model group were used to
      construct UV radiation eyeball models. Twelve rats in model group and 3 rats in
      control group were sacrificed at day 1, 3, 5 and 7, and the expression of p53,
      Bax and Bcl-2 in LECs was detected by RT-qPCR. There was no significant
      difference in p53 expression between model and control group on day 1 (P>0.05),
      while expression level of p53 was significantly higher in model than in control
      group at day 3, 5 and 7 (P<0.05), and the highest expression level was found on
      day 7 (P<0.05). Relative expression level of Bax in model group was significantly
      higher than that in control group (P<0.05), and the highest expression level was
      found on day 7 (P<0.05). On day 1, expression level of Bcl-2 in model group was
      significantly lower than that in control group (P<0.05), but it began to rise on
      day 3 but did not differ significantly from the control group (P>0.05), and was
      significantly higher in model than in control group on day 5 and 7 (P<0.05), and
      the highest expression level was observed on day 7 (P<0.05). Linear correlation
      analysis showed that there was a positive correlation between p53, Bax and Bcl-2
      expression and UV exposure time in LEC (r=0.82, 0.90, 0.95, P<0.05). Expression
      levels of p53, Bax, and Bcl-2 in LEC of rats are positively correlated with the
      time after UV irradiation, suggesting that UV could induce apoptosis of LEC by
      promoting p53, Bax and Bcl-2 expression.

PMID- 30186473
TI  - Impact of G-CSF on expressions of Egr-1 and VEGF in acute ischemic cerebral
      injury.
AB  - The aim of the present study was to investigate the protective effect of
      granulocyte colony-stimulating factor (G-CSF) on acute ischemic cerebral injury,
      and its mechanism through the impact of G-CSF on early growth response-1 (Egr-1)
      and vascular endothelial growth factor (VEGF) expressions. Male Sprague-Dawley
      (SD) rats were divided them into three groups, i.e., the sham, model and G-CSF
      groups to measure the effect of G-CSF on the volume of cerebral infarction and
      level of lactate dehydrogenase (LDH) in rats. Hematoxylin and eosin (H&E)
      staining method was performed for histopathological examination. Reverse
      transcription-polymerase chain reaction (RT-PCR) and western blot analysis were
      used to detect the mRNA and protein expressions of Egr-1 and VEGF in different
      groups. Furthermore, Statistical Product and Service Solutions (SPSS) 17.0
      software was applied to detect the differences in the expression of Egr-1 and
      VEGF between the two groups. Compared with the sham group, we found that the
      volume of cerebral infarction and LDH content in the model group were
      significantly elevated. By contrast, in the model group, those indicators in the
      G-CSF group were obviously decreased. H&E staining results also showed that G-CSF
      could decrease the necrotic area in cerebral infarction and the incidence of
      inflammation, and sustain the integrity of the molecular structure.
      Immunofluorescence staining results revealed that the protein expressions of Egr
      1 and VEGF in the model group were all significantly decreased, while those in
      the G-CSF group were remarkably elevated. RT-PCR and western blot analysis
      revealed that the mRNA and protein expressions of Egr-1 and VEGF in the model
      group were decreased obviously, but those in the G-CSF group were elevated
      significantly, and the differences between the two groups showed statistical
      significance (P<0.05). G-CSF manifests a significant protective effect on the
      acute ischemic cerebral injury, which may be realized through its effect on the
      expressions of Egr-1 and VEGF.

PMID- 30186474
TI  - Mesalazine suppository for the treatment of refractory ulcerative chronic
      radiation proctitis.
AB  - The aim of the present study was to investigate the safety and efficacy of
      mesalazine suppository in the treatment of refractory ulcerative chronic
      radiation proctitis (CRP). In total, 10 refractory ulcerative CRP patients who
      did not respond to previous medical treatments were recruited for the present
      study and were treated with mesalazine suppository (0.5 g) twice daily for 24
      weeks. For each patient, the severity of clinical symptoms and endoscopic
      appearance was assessed before and after the treatment. For symptom scoring, the
      reductions in the mean total symptom score (pre- vs. post-treatment, 8.20 vs.
      0.90; P<0.01), rectal bleeding score (2.40 vs. 0.30; P<0.01), rectal pain score
      (2.00 vs. 0.50; P<0.01), stool frequency score (2.00 vs. 0.10; P<0.01) and
      tenesmus score (1.80 vs. 0.00; P<0.01) were all statistically significant. For
      mucosal damage scoring, there was a reduction in the mean scores for total scores
      (9.22 vs. 5.22; P<0.01), telangiectasia (2.78 vs. 1.89; P=0.009), edema (2.89 vs.
      1.78; P=0.001) and ulceration (2.44 vs. 0.89; P=0.003). However, statistically
      reductions in the median symptom scores were not observed for stenosis (0.78 vs.
      0.67; P=0.347) and necrosis (0.33 vs. 0.00; P=0.081). Furthermore, no adverse
      events were observed during and after the treatment. The topical mesalazine
      suppository may be a safe and effective treatment for CRP, particularly for
      patients with deep ulcers. Adequately randomized controlled trials are required
      to confirm the results of the present study.

PMID- 30186475
TI  - Percutaneous renal artery stent implantation in the treatment of atherosclerotic
      renal artery stenosis.
AB  - We aimed to investigate the clinical curative effect of percutaneous renal artery
      stent implantation (PTRAS) in the treatment of atherosclerotic renal artery
      stenosis (ARAS), and to analyze the factors influencing the curative effect of
      PTRAS. A total of 230 patients with unilateral or bilateral renal artery stenosis
      were retrospectively analyzed. According to whether adverse cardiogenic or
      nephrogenic events occurred, 230 patients were divided into two groups to analyze
      the risk factors of adverse cardiogenic or nephrogenic events. The blood pressure
      of patients at each time-point after operation was decreased significantly
      compared with that before operation (P<0.01). The levels of serum creatinine
      (SCr) at 24 h and 36 months after PTRAS were slightly increased compared with
      that before operation (P>0.05). The estimated glomerular filtration rate (eGFR)
      at each time-point after operation was slightly decreased compared with that
      before operation, but the difference was not statistically significant (P>0.05).
      Renography showed that GFR on the side of stent implantation at 36 months after
      PTRAS had no significant change compared with that before operation (P>0.05), but
      GFR on the unaffected side without receiving PTRAS was significantly increased
      compared with that before operation (P=0.0014). During the 36-month follow-up,
      there were a total of 56 cases of adverse cardiogenic or nephrogenic events.
      Multivariate regression analysis results showed that adverse cardiogenic or
      nephrogenic events after PTRAS were obviously associated with age (>=65 years
      old), Charlson comorbidity index (CCI) score (>=2 points), diabetes mellitus,
      stroke and congestive heart failure (CHF) (P<0.05). In conclusion, PTRAS can
      effectively control the blood pressure and reduce the types of antihypertensive
      drugs used by patients with ARAS, but it has no definitely protective effect on
      renal function. Age (>=65 years old), CCI score (>=2 points), diabetes mellitus,
      stroke and CHF are risk factors leading to adverse cardiogenic or nephrogenic
      events after PTRAS.

PMID- 30186476
TI  - LncRNA MEG3 overexpression inhibits the development of diabetic retinopathy by
      regulating TGF-beta1 and VEGF.
AB  - In view of the high incidence of diabetic retinopathy and the functionality of
      long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3) in different
      disease models, the present study aimed to investigate the role of MEG3 in
      diabetic retinopathy. In the study, patients with diabetic retinopathy, diabetic
      patients without retinopathy as well as healthy people were included. Fasting
      blood was extracted from each participant. Serum MEG3 levels were detected by
      everse transcription-quantitative polymerase chain reaction (RT-qPCR) and serum
      vascular endothelial growth factor (VEGF) and transforming growth factor-beta1
      (TGF-beta1) levels were detected by ELISA. Also, the effects of high glucose
      treatment on the expression of MEG3 and VEGF and the effects of MEG3
      overexpression on expression of VEGF and TGF-beta1 in high glucose-treated ARPE
      19 cells were detected by RT-qPCR and western blot analysis to determine the mRNA
      and protein levels, respectively. It was indicated that serum levels of MEG3 were
      significantly lower, while the serum levels of VEGF and TGF-beta1 were
      significantly higher in patients with diabetic retinopathy and diabetic patients
      without retinopathy compared with the healthy controls. Furthermore, slight
      differences were found between patients with diabetic retinopathy and diabetic
      patients without retinopathy; however, these differences were not significant.
      The findings indicated that high glucose upregulated the expression of VEGF mRNA
      and downregulated the expression of MEG3, MEG3 overexpression reduced the
      increased expression levels of VEGF and TGF-beta1 induced by high glucose
      treatment. Therefore, it was concluded that lncRNA MEG3 overexpression may
      inhibit the development of diabetic retinopathy by inhibiting TGF-beta1 and VEGF
      expression.

PMID- 30186477
TI  - Imaging manifestations of B-mode ultrasound combined with CT in tuberculous
      pleuritis patients and the diagnostic value.
AB  - Clinical diagnostic values of B-mode ultrasound and computed tomography (CT) for
      tuberculous pleuritis were investigated. A total of 685 patients clinically
      diagnosed with tuberculous pleuritis in Yantaishan Hospital from January 2012 to
      August 2016 were selected as study subjects. The patients were examined by B-mode
      ultrasound and CT. The accuracy of B-mode ultrasound and CT in the diagnosis of
      tuberculous pleuritis was evaluated and the benefit-cost ratios of the two
      auxiliary diagnostic methods were compared. According to the imaging diagnostic
      results of 685 tuberculous pleuritis patients, B-mode ultrasound examinations
      identified 415 cases with tuberculous pleuritis and the accuracy rate was 60.15%.
      CT examinations identified 501 cases with the tuberculous pleuritis and the
      accuracy rate was 70.07%. The combined use of these two methods identified 546
      cases with the tuberculous pleuritis and the accuracy rate was significantly
      increased to 85.99%. B-mode ultrasound imaging findings showed that the lesions
      of tuberculous pleuritis were localized on the right pleural cavities and the
      majority of images presented the free type; multiple anechoic areas were seen in
      the effusion. CT findings indicated obvious free effusion in the pleural
      cavities, local thickening of the pleural cavities, encapsulated pleural effusion
      and extensive pleural adhesion, thickening and calcification. Both B-mode
      ultrasound and CT examinations can be used to accurately diagnose tuberculous
      pleuritis and the combined diagnosis can significantly improve the accuracy.

PMID- 30186478
TI  - Cilostazol on the expression of ICAM-1, VCAM-1 and inflammatory factors in plasma
      in patients with thromboangiitis obliterans.
AB  - The effects of cilostazol on the expression of intercellular adhesion molecule-1
      (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and inflammatory factors in
      plasma in patients with thromboangiitis obliterans (TAO) were studied. Plasma
      viscosity, fibrinogen, total cholesterol (TC) and triglyceride (TG) were detected
      for the healthy control, TAO and cilostazol groups, respectively. Results showed
      that compared with those in the control group, the plasma viscosity, fibrinogen,
      TC and TG levels in TAO group were significantly increased. By contrast, compared
      with those in TAO group, the plasma viscosity, fibrinogen, TC and TG levels in
      the cilostazol group were significantly decreased. ELISA results revealed that
      ICAM-1 and VCAM-1 expression levels in TAO group were obviously increased
      compared with those in control group. ICAM-1 and VCAM-1 expression levels in
      cilostazol group were obviously decreased compared with those in TAO group.
      According to RT-PCR, the mRNA expression levels of IL-1beta, IL-6 and TNF-alpha
      in TAO group were significantly higher than those in control group, while the
      levels in cilostazol group were significantly decreased compared with those in
      TAO group. In addition, RT-PCR and western blotting proved that expression of
      both mRNA and protein of ICAM-1 and VCAM-1 in TAO group was significantly
      increased and obviously decreased after administration of cilostazol. The results
      of analysis of variance showed that the differences of ICAM-1 and VCAM-1
      expression was statistically significant among the control, TAO and cilostazol
      groups (p<0.01). Cilostazol can significantly reduce the TAO-induced abnormal
      increase in ICAM-1, VCAM-1 and inflammatory factor expression in plasma in
      patients. It was proven that cilostazol has a good anti-TAO effect.

PMID- 30186479
TI  - Immunomagnetic enrichment to evaluate the role of home environment specimens in
      transmission of enterovirus 71.
AB  - Enterovirus 71 (EV71) immunomagnetic enrichment technique and routine detection
      methods were combined to detect swab environmental specimens to elucidate the
      role of environmental specimens in the spread of EV71. Immunomagnetic beads with
      specific enrichment of EV71 virus were prepared, then the beads were used to
      absorb the EV71 virus from environmental samples. Obtained immunomagnetic bead
      virus complexes were detected by RT-PCR, RT-qPCR and cell culture. Isolated virus
      were subjected to VP1 full-length amplification and homology analysis was
      performed. A total of 4 ug of EV71 monoclonal antibody was mixed with 50 ul
      magnetic beads, and the highest coating efficiency was reached after incubating
      at room temperature for 2 h. Satisfactory enrichment effect was achieved by
      adding 50 ul immunomagnetic beads to 1.5 ml sample and shaking at room
      temperature for 2 h. The method of EV71 enrichment has high sensitivity and
      specificity. A total of 346 specimens after enrichment by immunomagnetic beads,
      the positive rates of RT-qPCR, RT-PCR and cell culture were 20.52, 5.78, and
      9.25%, respectively, which were also significantly higher than those before
      enrichment (15.90, 3.47 and 4.05%; P<0.05). After enrichment with immunomagnetic
      beads, isolation rate of EV71 virus from case specimens and home environment
      specimens increased from 27.45 to 43.14% and from 0 to 5.29%, respectively. In
      home environment-positive specimens, positive rate of toys and stationery was
      high (52.00 and 24.00%, respectively). In kindergarten environmental samples, the
      positive rate of RT-qPCR was 6.12%, and EV71 virus was not isolated. Sequence
      analysis showed that the nucleotide homology of case isolates and home
      environment isolates was 98.0-100%.

PMID- 30186480
TI  - Effect of intraperitoneal or intracerebroventricular injection of streptozotocin
      on learning and memory in mice.
AB  - Alteration of behavior and PSD proteins in cerebral cortex and hippocampal
      synaptosome in the Alzheimer's disease (AD) mouse model were determined. AD was
      established by intraperitoneal injection of streptozotocin (STZ) in neonatal mice
      (intraperitoneal AD group) or intracerebroventricular injection of STZ in adult
      mice (intracerebroventricular AD group). Body weight and blood sugar level were
      measured. Following Morris water maze (MWM) test and fear-conditioning test,
      cerebral cortex and hippocampus tissues were collected and the levels of PSD95
      and shank3 proteins in these tissues were measured by western blot analysis. The
      body weight was reduced and the blood sugar concentration was increased in the
      intraperitoneal AD group compared with the control group. In contrast, the body
      weight was reduced, while the blood sugar concentration was not increased in the
      intracerebroventricular AD group compared with the control group. Escape latency
      in both AD groups was extended compared with the control group. The freezing time
      in the intraperitoneal AD group was increased, while in the
      intracerebroventricular AD group, the freezing time was reduced. PSD95 and shank3
      proteins in the cerebral cortex in both AD groups were decreased compared with
      the control group. PSD95 in the hippocampus was reduced in both AD groups
      compared with the control group. Shank3 in the hippocampus in the
      intracerebroventricular AD group was significantly reduced compared with the
      control group. Intraperitoneal injection of STZ in neonatal mice led to elevated
      blood sugar, impaired spatial memory and enhanced emotional memory when they
      become adults. In contrast, intracerebroventricular injection of STZ in adults
      directly led to deteriorated spatial and emotional memory without alteration of
      blood sugar content, which could be associated with the changes of PSD95 and
      shank3 proteins in hippocampus.

PMID- 30186481
TI  - Immunohistochemical profile of long-standing traumatic retinal detachment in
      atrophic globe in a young patient.
AB  - Photoreceptor cell death is the ultimate cause of irreversible vision loss in
      retinal detachment (RD). The present study aimed to investigate the retinal
      changes in a case of long-standing traumatic RD in a young patient. The RD
      induced atrophic globe was examined following enucleation. A control eye acquired
      from a deceased donor (normal histology; age- and sex-matched) was evaluated
      correspondingly. Frozen sections of retina tissue were assessed by
      immunofluorescence staining. The atrophic retina demonstrated structural
      disruption along with reduction in the retinal outer nuclear layer/inner nuclear
      layer thickness ratio. Photoreceptor degeneration was noted with complete loss of
      the outer segment of short-wavelength sensitive (S) cones. In addition, Muller
      cell hypertrophy was observed across the retinal nuclear layers. These results
      indicate that RD without successful medical treatment may lead to retinal atrophy
      associated with disruption of retinal integrity, dramatic S cones loss and
      subretinal gliosis. Further clarifications of the mechanisms underlying
      photoreceptor cell death and glial cell reprogramming may facilitate the design
      of novel therapeutic strategies for RD.

PMID- 30186482
TI  - Serum exosomal miR-328, miR-575, miR-134 and miR-671-5p as potential biomarkers
      for the diagnosis of Kawasaki disease and the prediction of therapeutic outcomes
      of intravenous immunoglobulin therapy.
AB  - The present study was conducted to screen serum exosomal microRNAs (miRNAs) for
      the early diagnosis of Kawasaki disease (KD) and to investigate their underlying
      mechanisms by analyzing microarray data under accession numbers GSE60965
      [exosomal miRNA, including three pooled serum samples from 5 healthy children, 5
      patients with KD and 5 patients with KD following intravenous immunoglobulin
      (IVIG) therapy] and GSE73577 (mRNA, including peripheral blood mononuclear cell
      samples from 19 patients with KD prior to and following IVIG treatment) from the
      Gene Expression Omnibus database. Differentially expressed miRNAs (DE-miRNAs) and
      genes (DEGs) were identified using the Linear Models for Microarray data method,
      and the mRNA targets of DE-miRNAs were predicted using the miRWalk 2.0 database.
      The functions of the target genes were analyzed using the Database for
      Annotation, Visualization and Integrated Discovery (DAVID). As a result, 65 DE
      miRNAs were identified with different expression patterns between the healthy
      children and patients with KD and between patients with KD and patients with KD
      following IVIG therapy. The target genes of 15 common DE-miRNAs were predicted.
      Following overlapping the target genes of DE-miRNAs with 355 DEGs, 28 common
      genes were identified and further screened to construct a network containing 30
      miRNA-mRNA regulatory associations. Of these associations, only miR-328-spectrin
      alpha, erythrocytic 1, miR-575-cyclic AMP-responsive element-binding protein 5/b
      1,4-galactosyltransferase 5/WD repeat and FYVE domain-containing 3/cystatin-A/C-X
      C motif chemokine receptor 1/protein phosphatase 1 regulatory subunit 3B, miR-134
      acyl-CoA synthetase long chain family member 1/C-type lectin domain family 1
      member A and miR-671-5p-tripartite motif containing 25/leucine rich repeat kinase
      2/kinesin family member 1B/leucine rich repeat neuronal 1 were involved in the
      negative regulation of gene expression. Functional analysis indicated that the
      identified target genes may be associated with inflammation. Accordingly, serum
      exosomal miR-328, miR-575, miR-134 and miR-671-5p may act as potential biomarkers
      for the diagnosis of KD and the prediction of outcomes of the IVIG therapy by
      influencing the expression of inflammatory genes.

PMID- 30186483
TI  - Efficacy and safety of baricitinib for active rheumatoid arthritis in patients
      with an inadequate response to conventional synthetic or biological disease
      modifying anti-rheumatic drugs: A meta-analysis of randomized controlled trials.
AB  - The purpose of the present meta-analysis was to assess the efficacy and safety of
      baricitinib for active rheumatoid arthritis (RA) in patients with an inadequate
      response or intolerance to conventional synthetic or biological disease-modifying
      anti-rheumatic drugs (DMARDs). A total of 7 randomized controlled trials (RCTs)
      were included. The primary effective outcome was the RA improvement to reach an
      American College of Rheumatology 20% (ACR20) response rate. The safety outcomes
      were composed of clinical laboratory parameters. All patients included received 4
      mg baricitinib once daily to treat RA for 12 or 24 weeks. The ACR20 response rate
      in the baricitinib group was significantly higher compared with that in the
      control group at 12 weeks [relative risk (RR), 1.77; 95% confidence interval
      (CI), 1.62-1.94; P<0.00001] and 24 weeks (RR, 1.76; 95% CI, 1.48-2.10;
      P<0.00001). Similarly, other effective outcome measures also exhibited
      significant improvements in the baricitinib group compared with those in the
      placebo group. Regarding the safety outcomes, no significant difference in
      adverse events (AEs) was identified at 12 weeks (P=0.14), but AEs were
      significantly higher in the baricitinib group compared with those in the control
      group at 24 weeks (P=0.03). Most laboratory values were significantly different
      between the baricitinib and placebo groups; however, the clinical significance of
      these changes remains to be determined. In summary, the present meta-analysis
      demonstrated that 4 mg baricitinib once daily was beneficial in patients with
      active RA with an inadequate response or intolerance to conventional synthetic or
      biological DMARDs. More high-quality RCTs are required to determine the sustained
      efficacy and the safety of baricitinib.

PMID- 30186484
TI  - Altered circulating T follicular helper cells in patients with chronic immune
      thrombocytopenia.
AB  - The present study aimed to illuminate the role of circulating T follicular helper
      (TFH) cells in patients diagnosed with chronic immune thrombocytopenia (cITP).
      Fifty-four patients with cITP and 30 age-matched healthy control subjects were
      enrolled in the present study. TFH cell frequencies, expression of CD4+ TFH cell
      associated cytokines, including interleukin (IL)-2, IL-4, IL-10 and IL-21 and
      associated regulatory mRNA expression levels including Bcl-6, c-Maf, Blimp-1 and
      PD-1 pre- and post-treatment with intravenous immunoglobulin and corticosteroids,
      were detected by flow cytometry, ELISA and reverse transcription-quantitative
      polymerase chain reaction, respectively. TFH cell frequencies of patients were
      significantly higher compared with healthy controls pre-treatment (P<0.05).
      Following treatment, significantly decreased percentages of TFH cells were
      present in cITP responders (P<0.05). Correlation analysis revealed that the
      number of TFH cells was negatively correlated with the platelet count in the
      peripheral blood. Furthermore, analysis of inflammatory cytokines indicated
      significant differences in serum interleukin (IL)-21 and IL-10 between pretreated
      patients and healthy controls (P<0.05). Additionally, transcription factor B-cell
      lymphoma (Bcl)-6, c-Maf and programmed death-ligand (PD)-1 mRNA expression levels
      were significantly different between cITP patients prior to treatment and the
      healthy controls (P<0.05). However, the expression levels of Bcl-6, C-Maf and PD
      1 mRNA were significantly changed post-treatment (P<0.05). These data
      demonstrated that circulating TFH cells and CD4+ TFH cell-associated cytokines
      may serve a role in cITP. The findings suggest that the overactivation of TFH
      cells may contribute to the immunopathogenesis of cITP, thus blocking the pathway
      of TFH cells may be reasonable for therapeutic intervention.

PMID- 30186485
TI  - Berberine inhibits cardiac remodeling of heart failure after myocardial
      infarction by reducing myocardial cell apoptosis in rats.
AB  - The effects of berberine on cardiac function of heart failure after myocardial
      infarction and its possible mechanism were investigated. The anterior descending
      branches of 50 female Wistar rats were ligatured to establish the model of heart
      failure after myocardial infarction. At 4 weeks after successful modeling, the
      rats were randomly divided into two groups receiving 4-week gavage with saline
      (Sal group) and berberine (Ber group), while the sham-operation group (Sham
      group) was set up. After 4 weeks, the hemodynamics and serum BNP in rats were
      measured. The hearts of rats were taken to detect the degree of myocardial
      fibrosis. The myocardial cell apoptosis was detected. The expressions and changes
      in myocardial apoptosis-related proteins, including Bcl-2, Bax and caspase-3,
      were detected. The expression and changes in GRP78, CHOP and caspase-12 in
      myocardial tissue were detected. The results showed that Berberine improved the
      cardiac function of rats after myocardial infarction. After myocardial
      infarction, myocardial fibrosis and apoptosis were observed around the infarction
      area, berberine improved the myocardial fibrosis and reduced cell apoptosis.
      Furthermore, berberine alleviated endoplasmic reticulum stress (ERS) after
      myocardial infarction. In conclusion, Berberine can inhibit the myocardium cell
      apoptosis of heart failure after myocardial infarction, and its mechanism may be
      realized by affecting the ERS in myocardial tissue of heart failure after
      myocardial infarction and CHOP and caspase-12 apoptotic signaling pathway,
      upregulating Bcl-2/Bax expression and downregulating caspase-3 expression, thus
      inhibiting the cardiac remodeling and protecting the cardiac function.

PMID- 30186486
TI  - Clinical significance of circulating tumor cells via combined whole exome
      sequencing in early stage cancer screening: A case report.
AB  - A newly-developed platform, integrating subtraction enrichment and immunostaining
      fluorescence in situ hybridization (SE-iFISH), was applied to analyze the
      clinical significance of circulating tumor cells (CTCs) for early screening of
      cancer in healthy people. The present case report describes one healthy
      individual who accepted a CTC peripheral blood test, and 8 CTCs/7.5 ml blood were
      detected. However, various conventional cancer biomarkers were all negative,
      including cervical cytological inspection, alpha-fetoprotein, cancer antigen (CA)
      125, CA19-9, carcinoembryonic antigen (CEA), CA15-3 and human papilloma virus. To
      explore the origin of the CTCs, whole exome sequencing was used to analyze the
      CTC variation spectrum. A total of 42 mutations were associated with cancer
      according to analysis in COSMIC (http://cancer.sanger.ac.uk/cosmic). The results
      revealed a high risk of tumor in the colorectum, stomach and breast (13, 12 and 6
      variations matched, respectively). In this individual, an intestinal polyp was
      discovered and removed by colonoscopy. The intestinal polyp was identified to be
      a hyperplastic polyp by pathological diagnosis. No lesions were discovered in the
      stomach and breast. No CTCs were detected in this patient's blood at 1 and 6
      months after removal of the lesions. This case indicates that CTC detection by SE
      iFISH has potential in early stage cancer screening, and the mutation spectrum of
      CTC assists the tracking of its sources.

PMID- 30186488
TI  - Pulmonary actinomycosis diagnosed by transbronchoscopic lung biopsy: A case
      report and literature review.
AB  - Pulmonary actinomycosis is a chronic, suppurative, granulomatous disease caused
      by Actinomyces israelii, an obligate anaerobe. The clinical manifestations and
      imaging characteristics of pulmonary actinomycosis lack specificity and can lead
      to confusion with tuberculosis and lung cancer. The present study reported a case
      of pulmonary actinomycosis diagnosed by transbronchoscopic lung biopsy and
      reviewed the literature on the disease. The clinical characteristics, signs,
      laboratory findings as well as progression, diagnosis and treatment in the case
      of pulmonary actinomycosis were analyzed. The patient was diagnosed by
      transbronchoscopic lung biopsy. After two weeks of antibiotic therapy, the cough
      was significantly improved and the patient's temperature returned to normal.
      Moreover, the lesion in the left lower lung was significantly smaller. Pulmonary
      actinomycosis is usually confused for tuberculosis and lung cancer. The present
      findings indicated that transbronchoscopic lung biopsy is a useful tool for
      diagnosing the disease. To conclude, doctors should have a clear enough
      understanding of the disease to prescribe empirical antibiotics and avoid
      unnecessary surgery.

PMID- 30186487
TI  - Bioinformatics identification of potential candidate blood indicators for
      doxorubicin-induced heart failure.
AB  - The care of individual patients requiring anthracyclines remains challenging as
      uncertainty persists on predictors of cardiotoxicity. The aim of the present
      study was to identify potential candidate blood indicators of doxorubicin-induced
      heart failure. The gene expression profiles of GSE40447 and GSE9128 microarray
      data were downloaded from the Gene Expression Omnibus database to identify
      differentially expressed genes (DEGs) using the R/Limma package or GEO2R.
      Functional and pathway enrichment analysis on DEGs were performed using DAVID
      database. The cardiovascular disease (CVD)-related DEGs were screen out based on
      the CardioGenBase database. The protein-protein interaction (PPI) network was
      constructed with STRING database and visualized by using Cytoscape. Then, the CVD
      related DEGs were validated by intersection analysis with DEGs in GSE9128. The
      overlapping DEGs with a consistent expression pattern in GSE40447 and GSE9128
      were identified as candidate indicators for doxorubicin-induced heart failure. A
      total of 516 DEGs potentially associated with doxorubicin-induced heart failure
      in GSE40447 were identified, which were mainly enriched in the gene ontology
      terms related to B cells, leukocytes, lymphocyte activation and B cell receptor
      signaling pathway. Of the DEGs, 42 were screened out as CVD-related DEGs by using
      CardioGenBase. Seven genes with high connectivity degree were presented in the
      PPI network. Finally, 5/6 CVD-related DEGs revealed by the intersection analysis
      were validated by GSE9128 and highlighted as candidate indicators of doxorubicin
      induced heart failure: CD163, CD28, SLC25A20, ANPEP and TLR5. Several genes,
      including the 5 previously mentioned, were proposed as potential candidate blood
      indicators for doxorubicin-induced heart failure. Further experimental
      validations are greatly warranted for future clinical application.

PMID- 30186489
TI  - Effect of saxagliptin on the expression of HIF-1alpha in the liver of diabetic
      rats with fatty liver.
AB  - The present study was designed to establish a rat model of type 2 diabetes
      mellitus (T2DM) complicated with fatty liver and to detect the expression of
      hypoxia-inducible factor-1alpha (HIF-1alpha) in liver tissue during the treatment
      with saxagliptin. Eighty male Wistar rats were randomly divided into two groups.
      One group was fed with high fat diet to establish T2DM model (n=40), and the
      other group was fed normally to serve as the control group (n=40). Successfully
      established rat T2DM models were randomly divided into two groups: The treatment
      group that received intraperitoneal injection of saxagliptin solution and the
      other the model group with normal breeding. Blood glucose, blood lipid, liver
      function and the expression of HIF-1alpha in liver tissue were detected. Levels
      of blood glucose in model treatment group were significantly higher than those in
      the control group (p<0.05). Levels of total cholesterol (TC), triglyceride (TG),
      low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol
      (HDL-C), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and
      gamma-glutamyl transferase (GGT) in model and treatment group were significantly
      higher than those in control group (p<0.05), but were significantly reduced with
      the prolonged treatment (p<0.05). Levels of TC, TG, LDL-C, HDL-C, AST, ALT and
      GGT and expression level of HIF-1alpha were significantly higher in the model
      group than in control group before 3 weeks of treatment (p<0.05), but no
      significant differences were found after 3 weeks of treatment (p>0.05).
      Expression level of HIF-1alpha was decreased with the prolonged treatment, and no
      significant difference in expression level of HIF-1alpha was found 3 weeks after
      treatment (p>0.05). In conclusion, HIF-1alpha is highly expressed in rats with
      T2DM and fatty liver. Saxagliptin can effectively improve blood glucose, blood
      lipid and liver function and reduce the protein expression of HIF-1alpha in
      diabetic rats with fatty liver.

PMID- 30186490
TI  - Flos Chrysanthemi Indici extract improves a high-sucrose diet-induced metabolic
      disorder in Drosophila.
AB  - Flos Chrysanthemi Indici (CI) is a traditional medicinal plant used in the
      treatment of inflammatory diseases. However, the pharmacological role of CI in
      metabolic diseases, especially in diseases induced by insulin metabolism
      disorders, remains poorly understood. In the present study, Drosophila
      melanogaster (Drosophila) were fed with high-sugar diet (HSD) to induce a model
      similar to Type 2 diabetes (T2D) in order to determine whether CI extracts
      improve the metabolic disorder. It was demonstrated that the CI extracts could
      improve growth rate, body size, lifespan, reproductive capacity and fat storage,
      and CI especially improved the fat metabolism and cell size in S6k and Akt1
      mutant flies. In conclusion, the present study provides novel evidence that CI
      may be an effective drug for the treatment of T2D.

PMID- 30186491
TI  - Luteolin decreases atherosclerosis in LDL receptor-deficient mice via a mechanism
      including decreasing AMPK-SIRT1 signaling in macrophages.
AB  - Lipid metabolism dysfunction and inflammatory infiltration into arterial walls
      are associated with the initiation and progression of atherosclerosis. Luteolin
      has been reported to possess anti-inflammatory actions and protect against tumor
      necrosis factor-alpha (TNF-alpha)-induced vascular inflammation, monocyte
      adhesion to endothelial cells and the formation of lipid-laden macrophages in
      vitro. However, the role of luteolin in atherosclerosis and the associated
      vascular inflammatory remains to be elucidated. The aim of the present study was
      to investigate the effects of luteolin on plaque development, lipid accumulation
      and macrophage inflammation low-density lipoprotein receptor-deficient (LDLR-/-)
      mice with atherosclerosis, as well as the underlying mechanisms in ox-induced THP
      1-derived macrophages. Firstly, 9-week-old male C57BL/6 mice were fed a standard
      chow diet, western diet or western diet supplemented with 100 mg/kg luteolin for
      14 weeks. The results of histological staining revealed that 100 mg/kg dietary
      luteolin ameliorated western diet-induced atherosclerotic plaque development and
      lipid accumulation in the abdominal aorta. Furthermore, total cholesterol,
      triglyceride and LDL-cholesterol levels were decreased in the plasma of western
      diet + luteolin mice compared with those fed with a western diet alone.
      Quantitative polymerase chain reaction analysis revealed that dietary luteolin
      inhibited the expression of cluster of differentiation 68, macrophage
      chemoattractant protein 2 and inflammatory cytokines, including interleukin-6 (IL
      6) and TNF-alpha. Mechanistically, luteolin decreased the total cholesterol level
      as well as macrophage chemokine and inflammatory cytokine expression in THP-1
      derived macrophages via AMP-activated protein kinase (AMPK)-Sirtuin (SIRT)1
      signaling following induction with oxidized low-density lipoprotein. The results
      of the present study suggest that luteolin prevents plaque development and lipid
      accumulation in the abdominal aorta by decreasing macrophage inflammation during
      atherosclerosis, which is mediated by mechanisms including AMPK-SIRT1 signaling.

PMID- 30186492
TI  - Effects of salvianolic acid on cerebral perfusion in patients after acute stroke:
      A single-center randomized controlled trial.
AB  - Hypoperfusion following acute stroke is common in the infarct core and periphery
      tissues. The present study evaluated the efficacy of salvianolic acid (SA) on the
      cerebral perfusion of patients who had suffered from acute stroke using perfusion
      weighted magnetic resonance imaging (PWI) to examine the blood perfusion of the
      affected brain tissue prior to and following treatment. Patients who were
      admitted to PLA 153 Central Hospital within 72 h of acute stroke symptom onset
      and had a Glasgow coma scale >=5 were randomized into two groups: SA and control
      groups. Patients in the SA group were administered SA 0.13 g/day for 14 days. PWI
      was performed for all patients at admission and post-treatment. The National
      Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) were
      applied to assess neurological function at admission and 3 months post treatment.
      A total of 159 patients were enrolled (85 patients in the SA group and 74
      patients in the control group). A total of 62 patients in the SA group and 51
      patients in the control group exhibited hypoperfusion in the ipsihemisphere of
      the diffusion-weighted magnetic resonance imaging (DWI) lesion. In addition,
      relative cerebral blood volume (rCBV), a ratio of the signal value of the region
      of interest in the same hemisphere of the DWI lesion to that of its mirror in the
      PWI CBV map, decreased significantly following treatment with SA compared with
      the control group in patients with hypoperfusion (P=0.02), which were indicated
      by PWI images at admission, in the DWI lesions or the surrounding areas.
      Additionally, there was no significant difference in patients with normal
      perfusion at admission in rCBV in DWI lesions or its surrounding area between the
      two groups at day 15. However, a significant improvement in NIHSS (P=0.001) and
      mRS (P=0.005) was indicated in the SA group compared with the control at day 90.
      The present study indicated that SA may improve the neurological dysfunction of
      patients with acute stroke, which may be explained by the increased perfusion of
      hypoperfused brain tissues.

PMID- 30186493
TI  - Tumor suppressor function of miR-483-3p on breast cancer via targeting of the
      cyclin E1 gene.
AB  - microRNA (miR)-483-3p has previously been demonstrated to be a tumor suppressor
      in many types of cancer cells, however it is unknown whether miR-483-3p is
      involved in the regulation of breast cancer. Therefore, the aim of the present
      study was to investigate the effects of miR-483-3p on breast cancer. The results
      demonstrated that the expression of miR-483-3p was decreased, especially in MCF-7
      cells. The results of CCK-8 assay and cell cycle analysis demonstrated that miR
      483-3p significantly reduced cell proliferation and inhibited MCF-7 cells in the
      G1 phase from entering the S phase (P<0.01). It was also demonstrated that Cyclin
      E1 (CCNE1) is a target gene of miR-483-3p using bioinformatics and a dual
      luciferase reporter assay. miR-483-3p inhibited the expression of CCNE1, cyclin
      dependent kinase 2, nuclear protein ataxia-telangiectasia (NPAT) and
      phosphorylated NPAT. Therefore, the results indicated that miR-483-3p functions
      as a tumor suppression in breast cancer and CCNE1 is its target gene. Downstream
      genes of CCNE1 were also repressed by miR-483-3p. Therefore, these findings
      suggest that miR-483-3p is a key factor in breast cancer.

PMID- 30186494
TI  - Quantification of nitric oxide by high-performance liquid chromatography
      fluorometric method in subgenomic hepatitis C virus-replicon expressing Huh7
      cells upon treatment with acetylsalicylic acid.
AB  - As nitric oxide (NO) expression levels are lower in hepatocytes compared with
      other cell types, it is difficult to quantify this compound via Griess assay. The
      aim of the present study was to quantify NO concentration in the cell culture
      medium from a subgenomic hepatitis C virus (HCV)-replicon expressing Huh-7 cell
      system using a high-performance liquid chromatography (HPLC)-fluorescence
      detector in the presence or absence of acetylsalicylic acid (ASA) treatment. HCV
      replicon cells were incubated with ASA (4 mM) for 24, 48 and 72 h. Thereafter,
      the medium was collected to measure nitrites (NO2-) as an indirect indicator of
      NO levels using diaminonaphtalene as a derivate agent. NO levels were
      significantly higher (1.7-fold) in Huh-7 replicon cells treated with ASA (72 h
      post-treatment) than untreated cells (P<0.05); NO inhibitor reduced ~30% the
      level of NO in Huh-7 replicon cells treated with ASA (48 h post-treatment;
      P<0.05). The findings suggested that the HPLC-fluorescence method provided an
      accurate and efficient measurement of NO production in Huh-7-HCV-replicon cells
      culture medium.

PMID- 30186495
TI  - Complement 3 glomerulonephritis in rheumatoid arthritis: A case report and follow
      up.
AB  - Glomerulonephritis (GN) caused by rheumatoid arthritis may manifest as various
      pathological types; however, to the best of our knowledge, rheumatoid arthritis
      associated complement 3 (C3)-GN has not been reported by any previous studies.
      C3GN is caused by dysregulation of the alternative pathway of complements, which
      is completely different from activation of the classic pathway of a typical
      autoimmune disease to cause renal damage. The present study describes a patient
      with a history of rheumatoid arthritis for 18 years, who presented with edema,
      proteinuria, hematuria, hypoproteinemia and a hypocomplementemic state. The
      pathological diagnosis was C3GN based on histological examination of a renal
      biopsy specimen. Hormone treatment on its own appeared to be effective and
      achieved complete clinical remission, while the follow-up of the condition
      remained stable.

PMID- 30186496
TI  - Identification of a novel TCOF1 mutation in a Chinese family with Treacher
      Collins syndrome.
AB  - Treacher Collins syndrome (TCS) is a severe congenital disorder characterized by
      craniofacial malformations, including cleft palate, hypoplasia of the facial
      bones, downward slanting of the palpebral fissures and malformation of the
      external and middle ear. Worldwide, 90% of cases of TCS are caused by mutations
      in the TCOF1 gene, which are inherited via an autosomal dominant pattern, while
      <2% cases are caused by POLR1D and POLR1C genes, which are inherited via
      autosomal dominant and autosomal recessive patterns, respectively. The present
      study describes the clinical findings and molecular diagnostics of a Chinese
      family with TCS. TCS was diagnosed in a 9-year-old female Chinese proband and her
      mother, while no craniofacial abnormalities were apparent in other family
      members. Exons of the TCOF1 gene and segregation analysis were used to examine
      causative mutations using the Sanger sequencing approach. A single novel
      heterozygous mutation in TCOF1 exon 3 splicing site c.165-1G>A was detected in
      the proband. Furthermore, the same mutation was identified in her mother, but not
      in other family members. These results suggest that c.165-1G>A is a novel
      heterozygous mutation of the TCOF1 gene that caused the development of TCS in the
      proband and her mother. The TCOF1 mutation that was identified in proband was
      inherited from her mother and so can be considered as de novo mutation.

PMID- 30186497
TI  - Activation of EphA4 induced by EphrinA1 exacerbates disruption of the blood-brain
      barrier following cerebral ischemia-reperfusion via the Rho/ROCK signaling
      pathway.
AB  - Vascular dementia (VD) is a syndrome characterized by progressive cognitive
      decline. According to previous studies, stroke is considered to be a risk factor
      for VD. The disruption of the blood-brain barrier (BBB) is pivotal to the
      pathology of stroke, as it contributes to post-stroke inflammation and edema. It
      has been reported that the Eph/Ephrin signaling pathway serves an important role
      in central nervous system injury. However, the role of EphrinA1/EphA4 signaling
      in BBB damage following ischemic stroke has not yet been reported. Oxygen-glucose
      deprivation/reperfusion was performed to detect changes in EphrinA1 and EphA4
      expression in human brain microvascular endothelial cells (HBMECs). Male mice
      were randomly divided into four groups [Sham, ischemia-reperfusion (I/R),
      I/R+EphrinA1 and I/R+EphA4] to observe the role of EphrinA1 and EphA4 under I/R
      conditions in vivo. The results of the present study revealed that the expression
      of EphrinA1 and EphA4 was significantly increased following I/R in vitro and in
      vivo. The administration of soluble ligand EphrinA1 enhanced CD68+ cell
      accumulation, brain edema and dysfunction of the BBB, with lower expression
      levels of zonula occludens-1 (ZO-1) and Claudin-5. In addition, EphrinA1-treated
      mice had a higher level of caspase-3 and a lower level of phosphorylated-protein
      kinase B. However, the effects of EphrinA1 were abolished by EphA4-Fc, an
      inhibitor of EphA4. These results suggested that EphrinA1 exerted its effects on
      I/R injury via the activated EphA4 receptor. In addition, EphrinA1 decreased ZO-1
      and Claudin-5 expression through the Rho/Rho associated kinase (ROCK) signaling
      pathway, which was attenuated by the pharmacological inhibition of Rho (C3
      transferase) or ROCK (Y-27632). In conclusion, the present study provides
      evidence that the activation of EphA4 induced by EphrinA1 contributes to BBB
      damage following ischemic stroke through the Rho/ROCK signaling pathway, which
      highlights a potential therapeutic strategy for ischemic stroke and may help the
      development of preventative interventions for VD.

PMID- 30186498
TI  - Association of cytokine gene polymorphisms with osteoarthritis susceptibility.
AB  - Osteoarthritis (OA) is a multifactorial disease characterized by low-grade
      inflammatory processes that are mediated initially by the cells and factors of
      the innate immune system. In addition to their key role in inflammation,
      cytokines contribute to the pathogenesis of OA through angiogenesis and
      chemotaxis. The purpose of the present case-control study was to investigate a
      possible association of four cytokine single nucleotide polymorphisms (SNPs), IL
      4R -3223C>T (rs2057768), IL-8 -251T>A (rs4073), IL-10 -1082A>G (rs1800896) and
      TNF -A-308G>A (rs1800629) with OA susceptibility. Genomic DNA was isolated from
      blood samples collected from 305 Romanian subjects (90 patients with OA and 215
      controls) and the genotyping of the SNPs was performed by TaqMan allelic
      discrimination polymerase chain reaction using predesigned assays. Our data
      indicated a significant association for IL-4R rs2057768 C>T SNP. The subjects
      that carried the CT genotype were at a higher risk for OA (OR 2.03, 95% CI: 1.21
      3.42, P=0.007) compared with those that had the CC genotype. Furthermore, the
      carriers of the T allele were at a 1.9 fold higher risk for OA (OR 1.92; 95% CI,
      1.17-3.17; P=0.009) in a dominant model. The association remained significant
      only for knee OA in the subgroups analysis. No correlations were observed between
      the other remaining SNPs and OA. The results suggested that the IL-4R rs2057768
      SNP could contribute to OA susceptibility in the Romanian population, providing
      novel evidence for the involvement of IL-4/IL-4R pair in the pathogenesis of OA.

PMID- 30186499
TI  - miR-148a inhibits pro-inflammatory cytokines released by intervertebral disc
      cells by regulating the p38/MAPK pathway.
AB  - The present study aimed to verify the expression and investigate the role of
      microRNA (miR)-148a in intervertebral disc degeneration (IDD) and explore the
      associated underlying mechanisms. Reverse transcription-quantitative polymerase
      chain reaction (RT-qPCR) was performed to investigate levels of miR-148a in the
      peripheral blood mononuclear cells (PBMCs) of patients with IDD. To investigate
      the role of miR-148a in IDD, a stable miR-148a-overexpression/underexpression
      human nucleus pulposus (NP) cell line was generated by transfection with miR-148a
      mimic/inhibitor. Then, NP cells were treated with LPS (10 uM) to induce
      inflammation. The mRNA expression level of miR-148a in NP cells was determined by
      RT-qPCR and the expression levels of p38 and p-p38 were measured using western
      blotting. The mRNA expression and supernatant level of pro-inflammatory
      cytokines, tumor necrosis factor (TNF-alpha), interleukin (IL)-1beta and IL-6,
      was evaluated by RT-qPCR and ELISA, respectively. The results indicated that miR
      148a was significantly downregulated in the PBMCs of IDD patients compared with
      healthy controls. In vitro upregulation of miR-148a in LPS-stimulated NP cells,
      by transfection with miR-148a mimic, resulted in inhibition of p-p38 expression;
      however, inhibition of miR-148a led to overexpression of p-p38. Meanwhile, the
      production of pro-inflammatory cytokines (TNF-alpha, IL-1beta and IL-6) was
      significantly reduced in miR-148a-overexpressing LPS-stimulated NP cells and
      significantly increased in miR-148a-underexpressing NP cells. In conclusion, miR
      148a inhibits pro-inflammatory cytokines released by intervertebral disc cells
      via regulation of the p38/mitogen-activated protein kinase pathway.

PMID- 30186500
TI  - Tetrandrine alleviates symptoms of rheumatoid arthritis in rats by regulating the
      expression of cyclooxygenase-2 and inflammatory factors.
AB  - The present study aimed to construct a rat model of rheumatoid arthritis (RA) to
      evaluate changes in pathology, the expression of inflammatory factors and
      regulation of signaling pathways. The protective effect of tetrandrine (Tet) on
      tissue lesions induced by RA was also investigated. A total of 60 Wistar rats
      (100-200 g) were randomly divided into six groups (n=10 per group), namely a
      blank (NC) group, model group, methotrexate (MTX) group (3 mg/kg body weight),
      high-dose Tet group (31.25 mg/kg body weight), medium-dose Tet group (18.75 mg/kg
      body weight) and low-dose Tet group (6.25 mg/kg body weight). A rat model of RA
      was induced via injection of 0.1 ml complete Freund's adjuvant into the right
      rear toe. Toe swelling rate, arthritis index and immune organ index were
      calculated. In addition, cyclooxygenase (COX)-2 expression at the mRNA and
      protein level in the peripheral blood mononuclear cells (PBMCs) of rats were
      determined by reverse transcription-quantitative polymerase chain reaction and
      western blot analysis, respectively. Serum concentrations of inflammatory factors
      were measured using enzyme-linked immunosorbent assays. It was observed that
      treatment with Tet alleviated the severity of rear toe swelling associated with
      RA in rats. Furthermore, Tet exerted anti-inflammatory and immunosuppressive
      effects in the rat model of RA. Tet also reduced the expression of COX-2 in PBMCs
      and lowered the concentrations of inflammatory factors in the serum of RA rats.
      The present data indicate that Tet may exert pharmacological effects in the
      treatment of RA. The mechanism of action of Tet may be associated with the
      regulation of inflammatory factors and the inhibition of immune organs.

PMID- 30186501
TI  - Biomechanical bearing-based typing method for osteonecrosis of the femoral head:
      ABC typing.
AB  - Type classification of osteonecrosis of the femoral head (ONFH) is important for
      collapse prediction in ONFH, which depends on a complexity of factors. At
      present, most typing is based on single factors, including the location or size
      of the necrosis, or the bone repair capacity after ONFH, and is therefore
      limited. The present study proposes an 'ABC' method for ONFH typing based on
      biomechanics and the stress distribution characteristics of the femoral head's
      bone trabeculae. In total, 132 ONFH patients (223 hips) were enrolled at
      Guanganmen Hospital (Beijing, China). Each of the hip joints included was
      subjected to computerized tomography and/or magnetic resonance imaging. The
      images with the maximum necrotic area in the coronal femoral head were selected,
      and the femoral head's maximum transverse diameter was divided into three pillars
      (A, B and C, from the outside to the inside) according to a 3:4:3 diameter ratio.
      ONFH was typed according to the number of pillars involved in the necrosis.
      Differences in the collapse rate of different ONFH types, and the correlation
      between the theoretical collapse risk and the observed collapse rate was
      analysed. The ONFH types significantly differed in their collapse rate
      (chi2=76.93, P<0.001) in the following order: A-C (88.6%)>AB (74.1%)>BC (52.4%)>A
      (50%)>B (9.5%)>C (0%). The collapse risk was significantly correlated with the
      collapse rate (correlation coefficient R=1). The types A-C and AB had high
      collapse rates/risks, whereas types B and C had a satisfactory prognosis. The ABC
      typing proposed in the present study is thus suitable for collapse risk
      prediction in ONFH. Type classification using this method may provide a valuable
      reference for selecting regimens for ONFH treatment.

PMID- 30186502
TI  - Acute bilateral vision deficit as the initial symptom in Guillain-Barre syndrome:
      A case report.
AB  - Guillain-Barre syndrome (GBS) is a rare autoimmune-mediated peripheral neuropathy
      with an acute onset. GBS is associated with posterior cranial nerve injury
      including the facial, oculomotor, glossopharyngeal and vagus nerves. A 43-year
      old female presented with worsening blurred binocular vision accompanied by
      diplopia, bilateral ptosis, speech difficulties, dysphagia, extremity numbness
      and weakness of the limbs. A neurological examination was conducted along with
      magnetic resonance imaging of the brain and spinal cord, electromyography,
      cerebrospinal fluid analysis and visual evoked potential tests, which led to a
      diagnosis of GBS. Following immunoglobulin administration, the patient's
      neurological deficiencies were markedly relieved and they were discharged
      following a 3-week observation period. To the best of our knowledge, this is the
      first reported case of GBS associated with cranial nerve damage presenting with
      bilateral visual deterioration as the initial symptom. It is necessary to
      emphasize that early diagnosis and commencing the immunological treatment in a
      timely manner resulted in a favorable prognosis for the patient.

PMID- 30186503
TI  - miR-192 is upregulated in T1DM, regulates pancreatic beta-cell development and
      inhibits insulin secretion through suppressing GLP-1 expression.
AB  - MicroRNAs (miRs) post-translationally regulate gene expression by specifically
      binding to the mRNA of their target genes. The aim of the present study was to
      determine the effect of miR-192 on pancreatic beta-cell development. The serum
      levels of miR-192 in type 1 diabetes mellitus (T1DM) and streptozotocin-induced
      rats were determined, and were revealed to be elevated compared with those in
      healthy patients and normal rats, respectively. Western blot and reverse
      transcription-quantitative polymerase chain reaction analysis indicated that miR
      192 suppressed the expression of glucagon-like peptide-1 (GLP-1), a potent
      insulin secretagogue. Ectopic expression of miR-192 inhibited cell proliferation
      and promoted apoptosis of NIT-1 cells, while miR-192 inhibitor had the opposite
      effect. Collectively, the present results revealed that miR-192 was elevated in
      T1DM, and is implicated in pancreatic beta-cell development through regulation of
      cell proliferation and apoptosis, thereby suppressing insulin secretion.
      Furthermore, miR-192 suppressed GLP-1 expression, thereby further promoting T1DM.
      The present study suggested that miR-192 is a novel molecular target for the
      management or prevention of T1DM.

PMID- 30186504
TI  - MicroRNA-126 accelerates IgE-mediated mast cell degranulation associated with the
      PI3K/Akt signaling pathway by promoting Ca2+ influx.
AB  - Mast cells (MCs) have been reported to serve a crucial role in allergic diseases,
      including asthma, allergic rhinitis and anaphylaxis. A previous study revealed
      that microRNA-126 (miR-126) was associated with airway hyperresponsiveness
      induced by house dust mites, however the molecular mechanisms were unclear. The
      present study aimed to investigate the effect of miR-126 on immunoglobulin E
      (IgE)-regulated MC degranulation and explore its underlying mechanisms. miR-126
      expression was quantified using a rat model in vivo and in rat peritoneal mast
      cells (RPMCs) in vitro. Overexpression or downregulation of miR-126 was
      established by transfection with miR-126 mimics or miR-126 inhibitors and MC
      degranulation was subsequently evaluated. The effect of miR-126 on protein kinase
      B (Akt) and phosphorylated Akt protein expression was examined by western blot
      analysis. The phosphoinositide 3-kinase (PI3K) inhibitor (LY294002) was used to
      determine the role of the PI3K/Akt signaling pathway. In addition, cytosolic
      calcium (Ca2+) levels were measured by a fura-2 assay. The results demonstrated
      that miR-126 expression was upregulated in the ear tissues of rats with allergic
      contact dermatitis and IgE-activated MCs. The overexpression of miR-126 in RPMCs
      was established following miR-126 mimic transfection. The release of beta
      hexosaminidase and histamine, markers of MC degranulation, were significantly
      increased in cells with miR-126 overexpression. The phosphorylation of Akt was
      significantly increased following transfection with miR-126 mimics in stimulated
      cells, however the signaling activation was abrogated by LY294002. In addition,
      Ca2+ influx was significantly promoted in stimulated RPMCs overexpressing miR
      126. These results indicate that miR-126 accelerated IgE-mediated MC
      degranulation associated with the PI3K/Akt signaling pathway by promoting Ca2+
      influx. This suggests that miR-126 may be a promising therapeutic target for the
      treatment of allergic skin diseases.

PMID- 30186505
TI  - Does Europe need paediatric virologists?

PMID- 30186506
TI  - Evaluating the proposal of paediatric virology: An interview with Professor Tina
      Dalianis, Professor of Tumour Virology at Karolinska Institutet.
AB  - Professor Tina Dalianis, Professor of Tumour Virology at Karolinska Institutet in
      Stockholm, Sweden, is a well-known virologist with a strong international
      reputation and seminal contributions in tumour virology in the fields of human
      papillomaviruses (HPVs) and polyomaviruses. According to Professor Dalianis, over
      the past decades virology has significantly contributed to the understanding of
      many infectious diseases in medicine. In addition, quite a few antiviral
      therapies have been developed in recent years that have been very helpful, while
      the study of viruses has also provided valuable information about their host
      cells and basic cell biology. She highlights the association of HPVs with
      tonsillar and base of tongue cancers, as well as their epidemic rise. She also
      refers to additional biomarkers, which are under investigation, in order to
      better individualise patient care, by for example, de-escalating or targeted
      therapy, whenever this is possible. She clarifies that the current prophylactic
      vaccines against HPVs are very efficient for the types they are directed against
      and she hopes that boys will also soon be vaccinated against HPVs, particularly
      in countries where there is a low percentage of girls being vaccinated. According
      to Professor Dalianis, the knowledge of virology is very useful in general
      paediatric practice; the proposal of paediatric virology as a medical
      subspecialty is absolutely correct and it would be very useful, as there is much
      to be done. In the context of the '4th Workshop on Paediatric Virology',
      Professor Tina Dalianis will give the plenary lecture of this scientific event
      and will focus on changes in the prevalence of different HPVs in genital and oral
      samples in some groups of youth in Sweden during the introduction of the vaccines
      against HPVs.

PMID- 30186507
TI  - Neonatology, paediatrics and paediatric virology on a British island: An
      interview with neonatologist Dr Prakash Thiagarajan (Isle of Man).
AB  - Dr Prakash Thiagarajan, consultant neonatologist and clinical director at Women's
      and Children's Division at Noble's Hospital on the Isle of Man, is one of the
      most talented neonatologists in the UK with a great experience in newer modes of
      infant ventilation and the application of technology in neonatal medicine and
      paediatrics. Under his leadership, the new neonatal intensive care unit (NICU) at
      Noble's Hospital is a state-of-the-art neonatal unit offering the very highest
      standards of care for critically ill babies on the island. Dr Thiagarajan
      highlights the re-emergence of continuous positive airway pressure (CPAP) as a
      key mode of ventilatory support for preterm infants and describes the current
      practice relating to the transport of the critically ill newborn and paediatric
      population. He reports the main milestones of the Isle of Man preparedness plan
      for influenza during the 2009 A/H1N1 influenza pandemic and he emphasises the
      role of immunisations and high level infection control measures in preventing
      future outbreaks of viral illnesses in children. He accepts that paediatric
      virology is an extremely important, yet underserved area of paediatrics and as
      with any clinical specialty, it is very important for effective two-way
      communications between frontline clinicians and academic researchers. He sums up
      suggesting the formation of the 'European Society for Paediatric Virology' in
      order to propagate knowledge and training in paediatric virology to health
      professionals, set standards in training, promote research and development and
      also raise public awareness. In the context of the '4th Workshop on Paediatric
      Virology', which will be held in Athens, Greece, on September 22nd, 2018, Dr
      Thiagarajan's plenary lecture will focus on antiviral drugs in the clinical
      management of children with influenza.

PMID- 30186508
TI  - The philosophy of paediatric teaching: An interview with Dr Nikolaos
      Myriokefalitakis, former Clinical Director of the 'Penteli' Children's Hospital
      in Athens (Greece).
AB  - Dr Nikolaos Myriokefalitakis, one of the most experienced paediatricians in the
      city of Athens, Greece, has worked as a consultant paediatrician at the 'P. & A.
      Kyriakou' Children's Hospital for more than 25 years, while during the 2004-2011
      period, he was the clinical director of the 1st Paediatric Department of the
      'Penteli' Children's Hospital. Under his leadership, in 2008, his department was
      renovated by 'Stavros Niarchos Foundation' and was organised as one of the most
      modern and exemplary national paediatric departments in Greece. Having the title
      of the 'teacher in paediatrics' by his junior Greek colleagues, he supports that
      clinical experience obtained through ward-based bedside teaching is the
      fundamental principle of paediatric teaching. He notes that paediatric diagnosis
      is performed thorough medical history and detailed physical examination of the
      patient and it is rarely established with the help of laboratory, common or
      specialised, investigations. According to Dr Myriokefalitakis, a modern
      paediatric department cannot function 'in a vacuum', but requires technological
      support, adequate medical and nursing personnel and team-working between
      paediatricians and experts on paediatric subspecialties and other basic
      specialties. He accepts that the current financial crisis in Greece has clearly
      affected negatively the clinical practice of primary as well as hospital-based
      paediatric care, while he regrets to note that as the years go by, physicians
      become more obsessed with defense medicine and technology. He suggests that it is
      necessary to distinguish paediatric virology from virology and he ends up
      encouraging the improvement of paediatric training in Greece highlighting the
      basic need to 'train the trainers' in medical education.

PMID- 30186509
TI  - The future of paediatric education.

PMID- 30186510
TI  - The future of medical education in neonatology, paediatrics and paediatric
      virology: An interview with Professor Alan Michael Weindling, Professor of
      Perinatal Medicine at the University of Liverpool.
AB  - Professor Alan Michael Weindling, Emeritus Professor of Perinatal Medicine at the
      University of Liverpool in the UK, is one of the pioneers of modern neonatal care
      worldwide with an enormous contribution to the care of premature babies in the
      city of Liverpool. During the last 3 decades, his contributions focused on the
      development of the clinical service, the training provided and the strong
      research achievements at Liverpool Women's Hospital NHS Trust, one of the most
      widely respected centres for neonatal medicine in western Europe. According to
      Professor Weindling, teaching a commitment to continuing lifelong learning as
      well as trying to make clinical care cost-effective is really important. He
      highlights the value of humility, holistic scientific approach, evidence-based
      medicine and multidisciplinary team working to neonatal and paediatric care.
      Looking back to neonatology as practiced in the 1990s, he accepts that since
      then, the overall standard of care has improved enormously. He supports that
      further neonatal care research is required for the prevention and treatment of
      acquired brain damage as well as on looking at ways of minimising stress for
      families, who have a child in an intensive care unit. He could see how for most
      trainees a module or series of lectures in paediatric infectious diseases would
      be helpful as part of their training and he estimates that in the future
      paediatric virology may become a specialist interest for a limited number of
      paediatric trainees. In the context of the '4th Workshop on Paediatric Virology',
      which will be held in Athens, Greece, on September 22nd, 2018, Professor
      Weindling will receive the '2018 Paediatric Virology Award in Neonatology and
      Medical Education'.

PMID- 30186512
TI  - Welcome to the September 2018 issue of Breathe.
AB  - The September issue of Breathe focuses on facets of respiratory care and
      compromise in the context of lifestyle http://ow.ly/nBkc30lb0S6.

PMID- 30186513
TI  - Never mind the biologics, just take the inhalers.
AB  - "It is a basic truth of the human condition that everybody lies. The only
      variable is about what." In paediatric asthma, patients don't take their
      treatments and doctors rarely ask the right questions. The end result is far too
      many child deaths. http://ow.ly/OaGK30kFtsD.

PMID- 30186514
TI  - Practical challenges and solutions to TB control in a lower-middle-income
      country: experiences from Mongolia.
AB  - Operational research, community initiatives and NGOs play an important role in
      improving TB care in low- and middle-income countries http://ow.ly/wpjO30kA3fu.

PMID- 30186515
TI  - Interstitial lung diseases: course report.
AB  - Faculty and delegates of an ERS course on ILD describe their experiences
      http://ow.ly/qy0s30l2xSW.

PMID- 30186516
TI  - Lifestyle interventions in prevention and comprehensive management of COPD.
AB  - : Chronic respiratory diseases are among the four major human chronic diseases.
      Tobacco smoke as well as environmental pollutants, infections, physical activity
      and nutritional status play a role in the prevalence, development and/or
      progression of chronic obstructive pulmonary disease (COPD). Changes in lifestyle
      are possible and may be beneficial in prevention and comprehensive management of
      COPD. Population-level interventions aimed at early diagnosis, promotion of
      vaccinations and prevention of infections, and reductions in smoking,
      environmental pollutants, physical inactivity, obesity and malnutrition may
      increase the number of life-years lived in good health. Educational aims: To
      improve awareness of the influence of lifestyle on natural history of COPD.To
      describe the effects of some interventions to modify lifestyle in prevention and
      management.To provide information on the main clinical results.To define
      recommendations and limitations.

PMID- 30186517
TI  - Marijuana and the lung: hysteria or cause for concern?
AB  - : Increasing cannabis use and legalisation highlights the paucity of data we have
      on the safety of cannabis smoking for respiratory health. Unfortunately,
      concurrent use of tobacco among marijuana smokers makes it difficult to untangle
      individual effect of marijuana smoking. Chronic cannabis only smoking has been
      shown in large cohort studies to reduce forced expiratory volume in 1 s/forced
      vital capacity via increasing forced vital capacity in chronic use contrary to
      the picture seen in tobacco smoking. The cause of this is unclear and there are
      various proposed mechanisms including respiratory muscle training secondary to
      method of inhalation and acute anti-inflammatory effect and bronchodilation of
      cannabis on the airways. While cannabis smoke has been shown to increase symptoms
      of chronic bronchitis, it has not been definitively shown to be associated with
      shortness of breath or irreversible airway changes. The evidence surrounding the
      development of lung cancer is less clear; however, preliminary evidence does not
      suggest association. Bullous lung disease associated with marijuana use has long
      been observed in clinical practice but published evidence is limited to a total
      of 57 published cases and only one cross-sectional study looking at radiological
      changes among chronic users which did not report any increase in macroscopic
      emphysema. More studies are required to elucidate these missing points to further
      guide risk stratification, clinical diagnosis and management. Key points:
      Cannabis smoking has increased and is likely to increase further with relaxation
      of legalisation and medicinal use of cannabinoids.Chronic marijuana smoking often
      produces symptoms similar to those of chronic tobacco smoking such as cough,
      sputum production, shortness of breath and wheeze.Cessation of marijuana smoking
      is associated with a reduction in respiratory symptoms and no increased risk of
      chronic bronchitis.Spirometry changes seen in chronic marijuana smokers appear to
      differ from those in chronic tobacco smokers. In chronic marijuana smokers there
      is an increase in FVC as opposed to a definite decrease in FEV1.Multiple case
      series have demonstrated peripheral bullae in marijuana smokers, but no
      observational studies have elucidated the risk.There is currently no clear
      association between cannabis smoking and lung cancer, although the research is
      currently limited. Educational aims: To update readers on legalisation of
      recreational and medicinal cannabis.To summarise the evidence base surrounding
      the respiratory effects of inhaled marijuana use.To provide clinicians with an
      understanding of the main differences between cannabis and tobacco to be able to
      apply this to patient education.To highlight common respiratory problems among
      cannabis users and the need for recreational drug history taking.

PMID- 30186520
TI  - An unusual pneumonia.
AB  - Can you diagnose this clinical case of a rare disease presenting as a very common
      disease? http://ow.ly/Trzu30kGzk6.

PMID- 30186518
TI  - The role of vitamin D in obstructive sleep apnoea syndrome.
AB  - : Obstructive sleep apnoea syndrome (OSAS) is a common disorder of multifactorial
      pathogenesis and is associated with obesity, diabetes and cardiovascular disease.
      Vitamin D is a fat-soluble vitamin with an important function in calcium
      absorption and homeostasis, which is also implicated in several nonskeletal
      conditions. The prevalence of vitamin D deficiency is increasing worldwide and is
      associated with similar metabolic disturbances to OSAS. Moreover, recent data
      suggest that in OSAS patients serum levels of vitamin D are lower compared with
      non-apnoeic subjects. However, the mechanisms linking vitamin D deficiency and
      OSAS are not completely understood and several hypotheses have been advanced. To
      date, a limited number of studies have assessed the association between lower
      serum concentrations of vitamin D and OSAS, and have reported inconsistent
      results. Similarly, contradictory results have been produced by studies which
      evaluated the effect of continuous positive airway pressure treatment on serum
      vitamin D levels. The aim of this review is to summarise current knowledge on the
      association between OSAS and vitamin D levels. Key points: Vitamin D
      insufficiency prevalence is increasing worldwide and presents with similar
      comorbidities and risk factors to OSAS.The nonskeletal actions of vitamin D may
      contribute to the development of OSAS through immune system modulation, myopathy
      and inflammation.Studies evaluating serum vitamin D concentrations in OSAS
      patients and the effect of CPAP treatment report contradictory results, often
      influenced by confounding factors, such as obesity.There appears to be potential
      for use of vitamin D supplementation in OSAS patients as a means of reducing the
      incidence of cardiovascular disease, a comorbidity common in both conditions.
      Educational aims: To assess the potential association between OSAS and serum
      levels of vitamin D.To discuss the pathogenetic mechanisms linking OSAS and
      vitamin D insufficiency.To illustrate the effect of CPAP treatment on vitamin D
      concentration in OSAS patients.

PMID- 30186519
TI  - Is there room for further innovation in inhaled therapy for airways disease?
AB  - : Inhaled medication is the cornerstone in the treatment of patients across a
      spectrum of respiratory diseases including asthma and chronic obstructive
      pulmonary disease. The benefits of inhaled therapy have long been recognised but
      the most important innovations have occurred over the past 60 years, beginning
      with the invention of the pressurised metered dose inhaler. However, despite over
      230 different device and drug combinations currently being available, disease
      control is far from perfect. Here we look at how innovation in inhaler design may
      improve treatments for respiratory diseases and how new formulations may lead to
      treatments for diseases beyond the lungs. We look at the three main areas where
      innovation in inhaled therapy is most likely to occur: 1) device engineering and
      design; 2) chemistry and formulations; and 3) digital technology associated with
      inhalers. Inhaler design has improved significantly but considerable challenges
      still remain in order to continually innovate and improve targeted drug delivery
      to the lungs. Healthcare professionals want see innovations that motivate their
      patients to achieve their goal of improving their health, through better
      adherence to treatment. Patients want devices that are easy to use and to see
      that their efforts are rewarded by improvements in their condition. Key points:
      The dictionary definition of innovation is the introduction of new things, ideas
      or ways of doing something. We show how this definition can be applied to inhaled
      therapy.We take a look at the past to see what drove innovation in inhaler design
      and how this has led to the current devices.We look at the current drivers of
      innovation in engineering, chemistry and digital technology and predict how this
      may translate to new devices.Can innovation help the healthcare professional
      manage their patients better?What does the patient expect from innovation in
      their device? Educational aims: To understand the importance of inhaled
      medication in the treatment of lung diseases.To understand how innovation has
      helped advance some of the devices patients use today from basic and inefficient
      designs.To understand the obstacles that prevent patients from receiving optimal
      treatment from their inhalers.To understand how innovation in inhaler design can
      lead to improved treatment for patients and widen the range of diseases that can
      be treated via the inhaled route.

PMID- 30186521
TI  - New members of the ECMC and lessons from the ATS Conference.
AB  - Meet the new members of the @EarlyCareerERS committee http://ow.ly/DfHA30kE7sk.

PMID- 30186522
TI  - From research question to dissemination: how to design, analyse and present study
      results.
AB  - The key for the success of a study lies in the careful design of all its
      different phases, from the statement of the objectives to the dissemination of
      the results http://ow.ly/5NbG30kHEnQ.

PMID- 30186523
TI  - Noninvasive ventilation in hypercapnic respiratory failure: from rocking beds to
      fancy masks.
AB  - A chronological account of some of the significant research into the application
      of NIV in acute hypercapnic respiratory failure over recent decades
      http://ow.ly/L5bZ30ktEG6.

PMID- 30186524
TI  - Radiology corner.

PMID- 30186525
TI  - Cardiorespiratory physiotherapy training and practice in Australia.
AB  - In 2018, Australia's population of approximately 25 million people is serviced by
      almost 32 000 registered physiotherapists [1]. Physiotherapists in Australia
      traditionally obtain their qualification via a 4-year, full-time equivalent
      undergraduate professional degree. This typically involves 2 or 3 years of full
      time, university-based education followed by full-time clinical education, during
      which the student is immersed in real-world clinical training under the
      supervision of physiotherapy clinicians.

PMID- 30186526
TI  - Respiratory nursing training in Croatia.
AB  - Nursing education in the Republic of Croatia is conducted at the secondary and
      higher education levels (post-secondary and tertiary). Croatian nursing education
      is in line with the recommendations of European Directives 2005/36/EC [1] and
      2013/55/EU [2]. High school (secondary level) education lasts for 5 years; after
      graduation, students are awarded the title "general care nurse" [3].

PMID- 30186527
TI  - Pneumology and sleep disordered breathing training in Portugal.
AB  - In Portugal, a medical degree takes 6 years, including a master's degree, ever
      since the Bologna Agreement of 2009. After this, and according to the Ordem dos
      Medicos (College of Physicians), one must complete 2 years of fully supervised
      clinical practice to be able to practice medicine. During this period, junior
      doctors rotate through several different medical and chirurgical specialties,
      after which and according to their grade on a national examination, they chose a
      specialty and location. Pneumology/respiratory medicine is one of the options and
      every year roughly 30 residents begin this 5-year specialty. Junior doctors
      usually choose where to perform their residency according to the subspecialties
      available in a particular hospital, their relationship with academia,
      opportunities for research projects and to go abroad, among other factors.

PMID- 30186528
TI  - Respiratory physiotherapy education in Italy: per aspera ad astra.
AB  - At the start of my career, following 3 years of undergraduate education in
      physiotherapy, it was crystal clear that I was more inclined to the respiratory
      field rather than musculoskeletal or neurological practice. At that time, after
      six enthusiastic months spent at Lacor Hospital (Gulu, Uganda) writing my
      graduation thesis, my remaining options were a 2-year Master's level degree
      (MSc), introduced in Italy in late 2004, randomly following some educational
      courses offered by the only Italian association of physiotherapists dealing with
      respiratory disease (Associazione Riabilitatori dell'Insufficienza Respiratoria;
      ARIR) or, eventually, deepening my understanding and, therefore, management of
      respiratory diseases through the available 1-year postgraduate track at the
      University of Milan (Milan, Italy). The MSc was about some nonspecific aspects of
      physiotherapy, such as health management, economics and general research issues,
      while the postgraduate course, established in 2006 and currently celebrating its
      13th edition, was offering 60 university training credits (Crediti Formativi
      Universitari; CFU), equivalent to approximately 1500 hours of work (lessons,
      individual study, preparation for the exam, research work, etc.). Taking into
      consideration the fact that a bachelor's degree in physiotherapy is obtained
      after 180 CFU and that the average amount of hours dedicated to the respiratory
      area corresponds, more or less, to less than 10% of the total CFU, it was not
      difficult for me to opt for the 1-year postgraduate track.

PMID- 30186529
TI  - Confidences de Salon: John Hurst.
AB  - ERS Monograph Chief Editor elect, John Hurst, gives an insight into his life
      http://ow.ly/NfDg30kVaM0.

PMID- 30186530
TI  - Testing your lungs: spirometry.
AB  - Your healthcare professional will show you how to blow into the spirometer before
      you begin. You may need to wear a soft clip over your nose to stop air leaking
      out of your nostrils. Before starting the test, you might be asked to breathe in
      deeply and out gently into the spirometer. You will then be asked to blow at
      least three times, but usually no more than 10 times, into the spirometer.

PMID- 30186531
TI  - Effect of Carotid Artery Morphological Variations on Cognitive Function.
AB  - Background: Carotid artery morphological variations (CAMV) are common variations
      on medical imaging; the effects of CAMV on cognition were still unknown. This
      study is aimed at investigating whether carotid artery morphological variations
      (CAMV) cause cognitive impairment. Methods: Hospitalized patients from March 2017
      to October 2017 who underwent digital subtract angiography (DSA) were divided
      into non-CAMV group, T-type group, K-type group, and C-type group according to
      their carotid artery morphology. Cognitive function in each group was evaluated
      with the Mini-Mental State Scale (MMSE), the Montreal Cognitive Assessment
      (MoCA), the Verbal Fluency Test (VFT), and the Digital Span Test (DST). Results:
      A total of 96 patients were included in the study (32 in non-CAMV group, 34 in T
      type group, 30 in K-type group, and none in C-group). The positive rate of MMSE
      in the non-CAMV group, the T-type group, and the K-type group was 15.6%, 14.7%,
      and 20.0%, respectively, with no statistical difference in the three groups (p =
      0.836). The positive rate of MoCA in the K-type group was significantly higher
      than that in the non-CAMV and the T-type groups (p < 0.001), but there was no
      significant difference between the non-CAMV group and the T-type group (p =
      0.826). The VFT, DST forward score, and backward score in the K-type group were
      significantly lower than those in the non-CAMV and the T-type groups (p < 0.001).
      Conclusions: K-type CAMV may cause cognitive impairment, and MoCA is superior to
      MMSE in identifying mild cognitive impairment caused by CAMV.

PMID- 30186532
TI  - Pretreatment Hepatitis C Virus NS5A/NS5B Resistance-Associated Substitutions in
      Genotype 1 Uruguayan Infected Patients.
AB  - Hepatitis C Virus (HCV) infection treatment has dramatically changed with the
      advent of direct-acting antiviral agents (DAAs). However, the efficacy of DAAs
      can be attenuated by the presence of resistance-associated substitutions (RASs)
      before and after treatment. Indeed, RASs detected in DAA treatment-naive HCV
      infected patients could be useful for clinical management and outcome prediction.
      Although the frequency of naturally occurring HCV NS5A and NS5B RASs has been
      addressed in many countries, there are only a few reports on their prevalence in
      the South American region. The aim of this study was to investigate the presence
      of RASs to NS5A and NS5B inhibitors in a DAA treatment naive cohort of Uruguayan
      patients infected with chronic hepatitis C and compare them with reports from
      other South American countries. Here, we found that naturally occurring
      substitutions conferring resistance to NS5A and NS5B inhibitors were present in
      8% and 19.2%, respectively, of treatment-naive HCV genotype 1 infected patients.
      Importantly, the baseline substitutions in NS5A and NS5B herein identified differ
      from the studies previously reported in Brazil. Furthermore, Uruguayan strains
      subtype 1a clustered within all major world clades, showing that HCV variants
      currently circulating in this country are characterized by a remarkable genetic
      diversity.

PMID- 30186534
TI  - Indoxyl Sulfate Elimination in Renal Replacement Therapy: Influence of Citrate-
      versus Acetate-Buffering Component during Bicarbonate Dialysis.
AB  - Indoxyl sulfate has been identified as a major factor in the dysregulation of
      several genes. It is classified as a poorly dialyzable uremic toxin and thus a
      leading cause in the poor survival rate of dialysis patients. A monocentric,
      prospective, open cohort study was performed in 43 male patients undergoing
      chronic renal replacement therapy in a single hemodialysis center. The aim of the
      study was to determine the influence of acetate- versus citrate-buffered dialysis
      fluids in hemodialysis (HD) and postdilution hemodiafiltration (HDF) settings on
      the elimination of indoxyl sulfate. Also, additional factors potentially
      influencing the serum concentration of indoxyl sulfate were evaluated. For this
      purpose, the predialysis and postdialysis concentration ratio of indoxyl sulfate
      and total protein was determined. The difference was of 1.15 (0.61; 2.10), 0.89
      (0.53; 1.66), 0.32 (0.07; 0.63), and 0.44 (0.27; 0.77) MUmol/g in acetate HD and
      HDF and citrate HD and HDF, respectively. Acetate HD and HDF were superior when
      concerning IS elimination when compared to citrate HD and HDF. Moreover, residual
      diuresis was determined as the only predictor of lower indoxyl sulfate
      concentration, suggesting that it should be preserved as long as possible. This
      trial is registered with EU PAS Register of Studies EUPAS23714.

PMID- 30186535
TI  - Comparison of structures among Saccharomyces cerevisiae Grxs proteins.
AB  - Glutaredoxins (Grxs) comprise a group of glutathione (GSH)-dependent
      oxidoreductase enzymes that respond to oxidative stress and sustain redox
      homeostasis. Saccharomyces cerevisiae Grx has a similar interaction patterns
      through its residues between the residues and the environment. The glutaredoxin
      domain covers 100% of the entire mature Grx1 and Grx8, while the glutaredoxin
      domain covers ~ 52% of the entire mature Grx6 and Grx7, which have approximately
      74 additional amino acids in their N-terminal regions, whereas Grx3 and Grx4 have
      two functional domains: glutaredoxin and thioredoxin. We have presented the
      prediction of disordered regions within these protein sequences. Multiple
      sequence alignment combined with a phylogenetic tree enabled us to specify the
      key residues contributing to the differences between Saccharomyces cerevisiae
      Grxs and the proportion symmetry.

PMID- 30186533
TI  - Circulating Levels of Omentin, Leptin, VEGF, and HGF and Their Clinical Relevance
      with PSA Marker in Prostate Cancer.
AB  - Background: Prostate cancer (PCa) is the first in terms of occurrence in Europe
      and second in Poland. The PCa risk factors include: genetic load, obesity, diet
      rich in fat, hypertriglyceridemia, and exposure to androgens. The prostate
      specific antigen (PSA) level may be elevated in prostate cancer or other prostate
      disorders. Fat tissue secretes adipocytokines, which increase the risk of cancer
      development and metastasis. Objectives: The aims of the study were to investigate
      the relationship between circulating levels of PSA, adipocytokines: omentin,
      leptin, hepatocyte growth factor (HGF), and vascular endothelial growth factor
      (VEGF) in serum obtained from patients with benign prostate hyperplasia (BPH) and
      prostate cancer (PCa). Methods: Forty patients diagnosed with BPH and forty
      diagnosed with PCa were assessed for the purpose of the study. The concentrations
      of omentin, leptin, HGF, and VEGF were determined using enzyme-linked
      immunosorbent assays (EIA). Results: PSA level was significantly higher in the
      PCa group than in BPH (18.2 versus 9 ng/mL, p < 0.01), while volume of prostate
      gland was significantly higher in the BPH group than in PCa (39.1 versus 31.1
      cm3, p = 0.02). HGF, VEGF, omentin, and leptin concentrations were significantly
      higher in PCa group than in BPH (359.5 versus 294.9 pg/mL, p = 0.04; 179.3 versus
      127.3 pg/mL, p < 0.01; 478.8 versus 408.3 ng/mL, p = 0.01; 15.7 versus 11.2
      ng/mL, p = 0.02, resp.). The multiple logistic regression analysis demonstrated
      that only omentin and PSA levels were independent predictors of PCa in studied
      subjects. Conclusions: PSA level as well as the level of omentin may be valuable
      markers of PCa with clinical significance, when compared to PSA.

PMID- 30186537
TI  - Poorer Prognosis of Idiopathic Pleuroparenchymal Fibroelastosis Compared with
      Idiopathic Pulmonary Fibrosis in Advanced Stage.
AB  - Objective: Idiopathic pleuroparenchymal fibroelastosis (IPPFE) is a rare disease
      characterized by predominant upper lobe pulmonary fibrosis of unknown etiology.
      However, the prognosis of IPPFE has not been discussed. We investigated the
      clinical characteristics and prognostic factors of IPPFE and idiopathic pulmonary
      fibrosis (IPF). Methods: We performed a retrospective cohort study on 375
      consecutive idiopathic interstitial pneumonia patients between April 2004 and
      December 2014. Among them, we diagnosed IPPFE and IPF patients using high
      resolution computed tomography radiological criteria. Results: Twenty-nine IPPFE
      patients (9 males, 20 females) and 67 IPF patients (54 males, 13 females) were
      enrolled. IPPFE patients were significantly more likely to be females and
      nonsmokers and had lower body mass index, lower values of predicted percentage of
      forced vital capacity (%FVC), and a higher residual volume-to-total lung capacity
      ratio than IPF patients. Survival analysis revealed that they had significantly
      poorer prognosis than IPF patients in GAP (gender, age, and physiology) stages II
      + III. %FVC and GAP index independently predict mortality in patients with IPPFE.
      Conclusions: Patients with IPPFE showed poorer prognosis in the advanced stage
      than patients with IPF. %FVC and GAP index are independent predictors of survival
      in patients with IPPFE.

PMID- 30186536
TI  - M cell-dependent antigen uptake on follicle-associated epithelium for mucosal
      immune surveillance.
AB  - The follicle-associated epithelium (FAE) covering mucosa-associated lymphoid
      tissue is distinct from the villous epithelium in cellular composition and
      functions. Interleukin-22 binding protein (IL-22BP), provided by dendritic cells
      at the sub-epithelial dome region, inhibits the IL-22-mediated secretion of
      antimicrobial peptides by the FAE. The Notch signal from stromal cells underneath
      the FAE diminishes goblet cell differentiation. These events dampen the mucosal
      barrier functions to allow luminal microorganisms to readily gain access to the
      luminal surface of the FAE. Furthermore, receptor activator of nucleic factor
      kappa B ligand (RANKL) from a certain stromal cell type induces differentiation
      into microfold (M) cells that specialize in antigen uptake in the mucosa.
      Microfold (M) cells play a key role in mucosal immune surveillance by actively
      transporting external antigens from the gut lumen to the lymphoid follicle. The
      molecular basis of antigen uptake by M cells has been gradually identified in the
      last decade. For example, GPI-anchored molecules (e.g., glycoprotein 2 (GP2) and
      cellular prion protein (PrPC)) and beta1-integrin facilitate the transport of
      specific types of xenobiotics. The antigen transport by M cells initiates antigen
      specific mucosal immune responses represented by the induction of secretory
      immunoglobulin A (S-IgA). Meanwhile, several invasive pathogens exploit M cells
      as a portal to establish a systemic infection. Recent findings have uncovered the
      molecular machinery of differentiation and functions of M cells.

PMID- 30186539
TI  - NOD2 Expression in Streptococcus pneumoniae Meningitis and Its Influence on the
      Blood-Brain Barrier.
AB  - Streptococcus pneumoniae meningitis is one of the most common disorders seen in
      clinical practice. It is believed that the brain tissue immune injury is caused
      by the expression of pattern-recognition receptors (PRR) which can further induce
      the release of other cytokines and inflammatory cascades. The aim of this study
      is to investigate the expression of nucleotide-binding oligomerization domain 2
      (NOD2) and inflammatory factors in rat brain tissues infected with Streptococcus
      pneumoniae and its influence on the blood-brain barrier (BBB) permeability. Rats
      were given an intracranial injection of Streptococcus pneumoniae to construct the
      Streptococcus pneumoniae meningitis rat models. The expression change curves of
      NOD2 and inflammatory factors at different time points (0 h, 12 h, 24 h, 48 h,
      and 7 d) after Streptococcus pneumoniae were evaluated by enzyme-linked
      immunosorbent assay (ELISA). Western blotting analysis and quantitative real-time
      polymerase chain reaction (qRT-PCR) were engaged to examine the expression of
      NOD2. Furthermore, the changing processes of pathological characteristics,
      nervous system score, cerebral oedema, and BBB permeability were observed. Our
      results showed that NOD2 expression began to increase in the 12 h after
      Streptococcus pneumoniae infection group, while the remaining inflammatory
      factors were not obviously increased. Meanwhile, the levels of NOD2, as well as
      inflammatory factors IL-1beta, TNF-alpha, and IL-6 were markedly elevated in 24 h
      and 48 h infection groups, which were consistent with the increases in BBB
      permeability and BWC, and the positive expression of NOD2 in the infected rat
      brain tissues was observed using immunohistochemistry (IHC). This study suggests
      that NOD2 might be related to the activation of inflammation pathways and the
      damage to the blood-brain barrier. NOD2 and inflammatory factors have played
      vital roles in the pathogenesis of Streptococcus pneumoniae meningitis.

PMID- 30186540
TI  - Transforaminal Epiduroscopic Basivertebral Nerve Laser Ablation for Chronic Low
      Back Pain Associated with Modic Changes: A Preliminary Open-Label Study.
AB  - Background: Chronic low back pain (CLBP) arising from degenerative disc disease
      continues to be a challenging clinical and diagnostic problem whether treated
      with nonsurgical, pain intervention, or motion-preserving stabilization and
      arthrodesis. Methods: Fourteen patients with CLBP, greater than 6 months,
      unresponsive to at least 4 months of conservative care were enrolled. All
      patients were treated successfully following screening using MRI findings of
      Modic type I or II changes and positive confirmatory provocative discography to
      determine the affected levels. All patients underwent ablation of the
      basivertebral nerve (BVN) using 1414 nm Nd:YAG laser-assisted energy guided in a
      transforaminal epiduroscopic approach. Macnab's criteria and visual analog scale
      (VAS) score were collected retrospectively at each follow-up interval. Results:
      The mean age was 46 +/- 9.95 years. The mean symptoms duration was 21.21 +/-
      21.87 months. The mean follow-up was 15.3 +/- 2.67 months. The preoperative VAS
      score of 7.79 +/- 0.97 changed to 1.92 +/- 1.38, postoperatively (P < 0.01). As
      per Macnab's criteria, seven patients (50%) had excellent, six patients (42.85%)
      had good, and one patient (7.14%) had fair outcomes. Conclusion: The
      transforaminal epiduroscopic basivertebral nerve laser ablation (TEBLA) appears
      to be a promising option in carefully selected patients with CLBP associated with
      the Modic changes.

PMID- 30186538
TI  - Respiratory Care for the Ventilated Neonate.
AB  - Invasive ventilation is often necessary for the treatment of newborn infants with
      respiratory insufficiency. The neonatal patient has unique physiological
      characteristics such as small airway caliber, few collateral airways, compliant
      chest wall, poor airway stability, and low functional residual capacity.
      Pathologies affecting the newborn's lung are also different from many others
      observed later in life. Several different ventilation modes and strategies are
      available to optimize mechanical ventilation and to prevent ventilator-induced
      lung injury. Important aspects to be considered in ventilating neonates include
      the use of correct sized endotracheal tube to minimize airway resistance and work
      of breathing, positioning of the patient, the nursing care, respiratory
      kinesiotherapy, sedation and analgesia, and infection prevention, namely, the
      ventilator-associated pneumonia and nosocomial infection, as well as prevention
      and treatment of complications such as air leaks and pulmonary hemorrhage.
      Aspects of ventilation in patients under ECMO (extracorporeal membrane
      oxygenation) and in palliative care are of increasing interest nowadays. Online
      pulmonary mechanics and function testing as well as capnography are becoming more
      commonly used. Echocardiography is now a routine in most neonatal units. Near
      infrared spectroscopy (NIRS) is an attractive tool potentially helping in
      preventing intraventricular hemorrhage and periventricular leukomalacia. Lung
      ultrasound is an emerging tool of diagnosis and can be of added value in helping
      monitoring the ventilated neonate. The aim of this scientific literature review
      is to address relevant aspects concerning the respiratory care and monitoring of
      the invasively ventilated newborn in order to help physicians to optimize the
      efficacy of care.

PMID- 30186541
TI  - Ferulated Arabinoxylans and Their Gels: Functional Properties and Potential
      Application as Antioxidant and Anticancer Agent.
AB  - In the last years, biomedical research has focused its efforts in the development
      of new oral delivery systems for the treatment of different diseases. Ferulated
      arabinoxylans are polysaccharides from cereals that have been gaining attention
      in the pharmaceutical field due to their prebiotic, antioxidant, and anticancer
      properties. The antioxidant and anticancer properties of these polysaccharides
      make them attractive compounds for the treatment of cancer, particularly colon
      cancer. In addition, ferulated arabinoxylans can form covalent gels through the
      cross-linking of their ferulic acids. Due to their particular characteristics,
      ferulated arabinoxylan gels represent an excellent alternative as colon-targeted
      drug delivery systems. The aim of the present work is to review the
      physicochemical and functional properties of ferulated arabinoxylans and their
      gels and to present the future perspectives for potential application as
      antioxidant and anticancer agents.

PMID- 30186543
TI  - NRF2 Activation Inhibits Both TGF-beta1- and IL-13-Mediated Periostin Expression
      in Fibroblasts: Benefit of Cinnamaldehyde for Antifibrotic Treatment.
AB  - Systemic fibrosing or sclerotic disorders are life-threatening, but only very
      limited treatment modalities are available for them. In recent years, periostin
      (POSTN), a major extracellular matrix component, was established by several
      studies as a novel key player in the progression of systemic fibrotic disease. In
      this research, we revealed the involvement of oxidative stress in the expression
      of POSTN induced by TGF-beta1 and IL-13 in dermal fibroblasts. We found that the
      antioxidant cinnamaldehyde activated the NRF2/HMOX1 pathway. Cinnamaldehyde also
      alleviated TGF-beta1- and IL-13-mediated production of reactive oxygen species
      and subsequent POSTN upregulation in dermal fibroblasts. In contrast, NRF2
      silencing abolished the cinnamaldehyde-mediated downregulation of POSTN. These
      results suggest that cinnamaldehyde is a broad inhibitor of POSTN expression
      covering both TGF-beta1 and IL-13 signaling. Cinnamaldehyde may thus be
      beneficial for the treatment of systemic fibrotic diseases.

PMID- 30186542
TI  - Impact of Obesity and Hyperglycemia on Placental Mitochondria.
AB  - A lipotoxic placental environment is recognized in maternal obesity, with
      increased inflammation and oxidative stress. These changes might alter
      mitochondrial function, with excessive production of reactive oxygen species, in
      a vicious cycle leading to placental dysfunction and impaired pregnancy outcomes.
      Here, we hypothesize that maternal pregestational body mass index (BMI) and
      glycemic levels can alter placental mitochondria. We measured mitochondrial DNA
      (mtDNA, real-time PCR) and morphology (electron microscopy) in placentas of forty
      seven singleton pregnancies at elective cesarean section. Thirty-seven women were
      normoglycemic: twenty-one normal-weight women, NW, and sixteen obese women,
      OB/GDM(-). Ten obese women had gestational diabetes mellitus, OB/GDM(+). OB/GDM(
      ) presented higher mtDNA levels versus NW, suggesting increased mitochondrial
      biogenesis in the normoglycemic obese group. These mitochondria showed similar
      morphology to NW. On the contrary, in OB/GDM(+), mtDNA was not significantly
      increased versus NW. Nevertheless, mitochondria showed morphological
      abnormalities, indicating impaired functionality. The metabolic response of the
      placenta to impairment in obese pregnancies can possibly vary depending on
      several parameters, resulting in opposite strains acting when insulin resistance
      of GDM occurs in the obese environment, characterized by inflammation and
      oxidative stress. Therefore, mitochondrial alterations represent a feature of
      obese pregnancies with changes in placental energetics that possibly can affect
      pregnancy outcomes.

PMID- 30186545
TI  - The Impact of Moderate Chronic Hypoxia and Hyperoxia on the Level of Apoptotic
      and Autophagic Proteins in Myocardial Tissue.
AB  - The redox imbalance and the consequent oxidative stress have been implicated in
      many pathological conditions, including cardiovascular diseases. The lack or the
      excess of O2 supply can alter the redox balance. The aim of the present study was
      to understand the heart responses to prolonged hypoxia or hyperoxia and how such
      situations may activate survival mechanisms or trigger cell death. Seven-week-old
      Foxn1 mice were exposed to hypoxia (10% O2), normoxia (21% O2), or hyperoxia (30%
      O2) for 28 days, then the heart tissue was excised and analyzed. The alterations
      in redox balance, housekeeping protein levels, and autophagic and apoptotic
      process regulation were studied. The D-ROM test demonstrated an increased
      oxidative stress in the hypoxic group compared to the hyperoxic group. The level
      of hypoxia inducible factor-1 (HIF-1alpha) was increased by hypoxia while HIF
      2alpha was not affected by treatments. Chronic hypoxia activated the biochemical
      markers of autophagy, and we observed elevated levels of Beclin-1 while LC3B-II
      and p62 were constant. Nevertheless, we measured significantly enhanced number of
      TUNEL-positive cells and higher Bax/Bcl2 ratio in hyperoxia with respect to
      hypoxia. Surprisingly, our results revealed alterations in the level of
      housekeeping proteins. The expression of alpha-tubulin, total-actin, and GAPDH
      was increased in the hypoxic group while decreased in the hyperoxic group. These
      findings suggest that autophagy is induced in the heart under hypoxia, which may
      serve as a protective mechanism in response to enhanced oxidative stress. While
      prolonged hypoxia-induced autophagy leads to reduced heart apoptosis, low
      autophagic level in hyperoxia failed to prevent the excessive DNA fragmentation.

PMID- 30186544
TI  - Remote Ischemic Preconditioning Ameliorates Acute Kidney Injury due to Contrast
      Exposure in Rats through Augmented O-GlcNAcylation.
AB  - Remote ischemic preconditioning (RIPC) is an adaptive response, manifesting when
      local short-term ischemic preconditioning reduces damage to adjacent or distant
      tissues or organs. O-linked beta-N-acetylglucosamine (O-GlcNAc) glycosylation of
      intracellular proteins denotes a type of posttranslational modification that
      influences multiple cytoplasmic and nuclear protein functions. Growing evidence
      indicates that stress can induce an acute increase in O-GlcNAc levels, which can
      be cytoprotective. The current study aimed to determine whether RIPC can provide
      renoprotection against contrast-induced acute kidney injury (CI-AKI) by
      augmenting O-GlcNAc signaling. We established a stable model of CI-AKI using 5/6
      nephrectomized rats exposed to dehydration followed by iohexol injection via the
      tail vein. We found that RIPC increased UDP-GlcNAc levels through the hexosamine
      biosynthetic pathway as well as global renal O-GlcNAcylation. RIPC-induced
      elevation of O-GlcNAc signaling ameliorated CI-AKI based on the presence of less
      tubular damage and apoptosis and the amount of reactive oxygen species. In
      addition, the use of alloxan, an O-GlcNAc transferase inhibitor, and azaserine, a
      glutamine fructose-6-phosphate amidotransferase inhibitor, neutralized the
      protective effect of RIPC against oxidative stress and tubular apoptosis. In
      conclusion, RIPC attenuates local oxidative stress and tubular apoptosis induced
      by contrast exposure by enhancing O-GlcNAc glycosylation levels; this can be a
      potentially useful approach for lowering the risk of CI-AKI.

PMID- 30186546
TI  - Corrigendum to "Circulating Levels of Sirtuin 4, a Potential Marker of Oxidative
      Metabolism, Related to Coronary Artery Disease in Obese Patients Suffering from
      NAFLD, with Normal or Slightly Increased Liver Enzymes".
AB  - [This corrects the article DOI: 10.1155/2014/920676.].

PMID- 30186547
TI  - Protective Effect of Matricaria chamomilla Ethanolic Extract on Hippocampal
      Neuron Damage in Rats Exposed to Formaldehyde.
AB  - Formaldehyde, as a frequently used compound in many applications, crosses the
      blood-brain barrier and leads to hippocampal cell death and memory impairment.
      This study investigates the effects of ethanolic extract of Matricaria chamomilla
      (MC) on passive avoidance learning induced by damaged hippocampal cells and
      evaluates the antioxidant traits of MC. The male Wistar rats were divided into
      six (6 in each) groups: control (10 mg/kg normal saline), 200 (200 mg/kg MC
      extract), 500 (500 mg/kg MC extract), F (10 mg/kg formaldehyde), F200 (10 mg/kg
      formaldehyde and 200 mg/kg MC extract), and F500 (10 mg/kg formaldehyde and 500
      mg/kg MC extract). Shuttle box assay was used for evaluation of passive avoidance
      learning. The apoptosis rate of hippocampal tissue, malondialdehyde (MDA) free
      radicals, and total antioxidant capacity was evaluated to determine the positive
      effect of the ethanolic extract of MC. We found that the ethanolic extract of MC
      reduced the cell death, time spent in a dark room, and MDA free radicals in the
      hippocampus, leading to increased total antioxidant capacity in this region. In
      conclusion, the ethanolic extract of MC could ameliorate formaldehyde-induced
      memory damage through decreasing cell death and MDA activity of the hippocampal
      region and increasing total antioxidant capacity.

PMID- 30186548
TI  - The Antidiabetic and Antinephritic Activities of Tuber melanosporum via
      Modulation of Nrf2-Mediated Oxidative Stress in the db/db Mouse.
AB  - Tuber melanosporum (TM), a valuable edible fungus, contains 19 types of fatty
      acid, 17 types of amino acid, 6 vitamins, and 7 minerals. The antidiabetic and
      antinephritic effects of TM and the underlying mechanisms related to oxidative
      stress were investigated in db/db mice. Eight-week oral administration of
      metformin (Met) at 0.1 g/kg and TM at doses of 0.2 and 0.4 g/kg decreased body
      weight, plasma glucose, serum levels of glycated hemoglobin, triglyceride, and
      total cholesterol and increased serum levels of high-density lipoprotein
      cholesterol in the mice, suggesting hypoglycemic and hypolipidemic effects. TM
      promoted glucose metabolism by increasing the levels of pyruvate kinase and
      hepatic glycogen. It also regulated the levels of inflammatory factors and
      oxidative enzymes in serum and/or the kidneys of the mice. Additionally, TM
      increased the expression of nuclear respiratory factor 2 (Nrf2), catalase, heme
      oxygenase 1, heme oxygenase 2, and manganese superoxide dismutase 2 and decreased
      the expression of protein kinase C alpha, phosphor-janus kinase 2, phosphor
      signal transducer and activator of transcription 3, and phosphor-nuclear factor
      kappaB in the kidneys. The results of this study reveal the antidiabetic and
      antidiabetic nephritic properties of TM via modulating oxidative stress and
      inflammation-related cytokines through improving the Nrf2 signaling pathway.

PMID- 30186551
TI  - Therapeutic Potential of Natural Antioxidants.

PMID- 30186549
TI  - Role of Oxidative and Nitro-Oxidative Damage in Silver Nanoparticles Cytotoxic
      Effect against Human Pancreatic Ductal Adenocarcinoma Cells.
AB  - Pancreatic ductal adenocarcinoma is one of the most aggressive human
      malignancies, where the 5-year survival rate is less than 4% worldwide.
      Successful treatment of pancreatic cancer is a challenge for today's oncology.
      Several studies showed that increased levels of oxidative stress may cause cancer
      cells damage and death. Therefore, we hypothesized that oxidative as well as
      nitro-oxidative stress is one of the mechanisms inducing pancreatic cancer
      programmed cell death. We decided to use silver nanoparticles (AgNPs) (2.6 and 18
      nm) as a key factor triggering the reactive oxygen species (ROS) and reactive
      nitrogen species (RNS) in pancreatic ductal adenocarcinoma cells (PANC-1).
      Previously, we have found that AgNPs induced PANC-1 cells death. Furthermore, it
      is known that AgNPs may induce an accumulation of ROS and alteration of
      antioxidant systems in different type of tumors, and they are indicated as
      promising agents for cancer therapy. Then, the aim of our study was to evaluate
      the implication of oxidative and nitro-oxidative stress in this cytotoxic effect
      of AgNPs against PANC-1 cells. We determined AgNP-induced increase of ROS level
      in PANC-1 cells and pancreatic noncancer cell (hTERT-HPNE) for comparison
      purposes. We found that the increase was lower in noncancer cells. Reduction of
      mitochondrial membrane potential and changes in the cell cycle were also
      observed. Additionally, we determined the increase in RNS level: nitric oxide
      (NO) and nitric dioxide (NO2) in PANC-1 cells, together with increase in family
      of nitric oxide synthases (iNOS, eNOS, and nNOS) at protein and mRNA level.
      Disturbance of antioxidant enzymes: superoxide dismutase (SOD1, SOD2, and SOD3),
      glutathione peroxidase (GPX-4) and catalase (CAT) were proved at protein and mRNA
      level. Moreover, we showed cells ultrastructural changes, characteristic for
      oxidative damage. Summarizing, oxidative and nitro-oxidative stress and
      mitochondrial disruption are implicated in AgNPs-mediated death in human
      pancreatic ductal adenocarcinoma cells.

PMID- 30186552
TI  - Clinical outcome of thymectomy in myasthenia gravis patients: A report from Iran.
AB  - Background: Myasthenia gravis (MG) is an autoimmune disease affecting
      acetylcholine postsynaptic receptor of voluntary muscles. Thymectomy is done in
      these patients and is a mainstay in the treatment of MG; however, the long-term
      result of surgery is still controversial. This study dealt with the investigation
      of the results of thymectomy in treatment, recovery and control of the symptoms
      of these patients. Methods: This study was performed through a retrospective
      method in patients suffering from MG who underwent trans-sternal thymectomy
      between 2011 and 2016. We conducted thymectomy, excision of mediastinal mass and
      contents of tissues between the right and left phrenic nerves for all patients.
      Then, the effect of various variables including age, sex, time interval between
      onset of disease and surgery, thymus pathology and the dosage of drug on clinical
      response after surgery was determined using various statistical tests. Results:
      47 patients including 26 men and 21 women with the mean age of 33.0 +/- 4.6 years
      have been investigated. The mean age of patients was 36.2 and 29.7 in men and
      women respectively (P = 0.041). Spiral chest computed tomography (CT) scan was
      present in 47 patients demonstrating mediastinal mass in 40 (85.1%) patients.
      Also, our pathological results showed thymic cells in aortopulmonary window
      contents of 4 patients. According to the results, the younger age of patients at
      the time of surgery, shorter time between diagnosis and thymectomy, being a woman
      and non-thymoma pathology were along with better clinical outcomes after
      thymectomy. Conclusion: Our study shows better clinical results of thymectomy in
      patients with normal chest CT scan and normal or atrophic thymus in pathologic
      reports. Generally, it seems that performing thymectomy in a shorter time
      interval after diagnosis of MG is beneficial. Moreover, in MG patients who do not
      suffer from thymoma, it is along with positive results.

PMID- 30186550
TI  - Neuroprotective Effects of dl-3-n-Butylphthalide against Doxorubicin-Induced
      Neuroinflammation, Oxidative Stress, Endoplasmic Reticulum Stress, and Behavioral
      Changes.
AB  - Doxorubicin (DOX) is a broad-spectrum antitumor drug while its use is limited due
      to its neurobiological side effects associated with depression. We investigated
      the neuroprotective efficacy of dl-3-n-butylphthalide (dl-NBP) against DOX
      induced anxiety- and depression-like behaviors in rats. dl-NBP was given (30
      mg/kg) daily by gavage over three weeks starting seven days before DOX
      administration. Elevated plus maze (EPM) test, forced swimming test (FST), and
      sucrose preference test (SPT) were performed to assess anxiety- and depression
      like behaviors. Our study showed that the supplementation of dl-NBP significantly
      mitigated the behavioral changes induced by DOX. To further explore the mechanism
      of neuroprotection induced by dl-NBP, several biomarkers including oxidative
      stress markers, endoplasmic reticulum (ER) stress markers, and neuroinflammatory
      cytokines in the hippocampus were quantified. The results showed that dl-NBP
      treatment alleviated DOX-induced neural apoptosis. Meanwhile, DOX-induced
      oxidative stress and ER stress in the hippocampus were significantly ameliorated
      in dl-NBP pretreatment group. Our study found that dl-NBP alleviated the
      upregulation of malondialdehyde (MDA), nitric oxide (NO), CHOP, glucose-regulated
      protein 78 kD (GRP-78), and caspase-12 and increased the levels of reduced
      glutathione (GSH) and activities of catalase (CAT), glutathione reductase (GR),
      and glutathione peroxidase (GPx) in the hippocampus of rats exposed to DOX.
      Additionally, the gene expression of interleukin-6 (IL-6), interleukin-1beta (IL
      1beta), and tumor necrosis factor-alpha (TNF-alpha) and protein levels of
      inducible nitric oxide synthase (iNOS) were significantly increased in DOX
      treated group, whereas DOX-induced neuroinflammation was significantly attenuated
      in dl-NBP supplementation group. In conclusion, dl-NBP could alleviate DOX
      induced anxiety- and depression-like behaviors via attenuating oxidative stress,
      ER stress, inflammatory reaction, and neural apoptosis, providing a basis as a
      therapeutic potential against DOX-induced neurotoxicity.

PMID- 30186553
TI  - Demographic features and clinical characteristics of patients with Parkinson's
      disease in Isfahan, Iran.
AB  - Background: Parkinson's disease (PD) is the second most common neurodegenerative
      disorder. Its worldwide incidence rate varies between 18 and 418 cases per 100000
      annually. This cross-sectional study was carried out with the aim to identify the
      clinical characteristics and demographic features of a huge number of patients
      with PD in Isfahan, Iran. Methods: The study was conducted on 987 patients with
      PD in Isfahan city and checklists were used to evaluate the demographic features
      and clinical characteristics of the patients. Results: The mean age of the
      patients at the time of sampling was 65.40 +/- 11.90 years. The study results
      indicated that the rate of PD among men with 67.3% was twice that of women with
      32.7%. The mean duration of the disease was 4.91 +/- 4.60 years. Conclusion: This
      study showed a considerable rate of PD among the individuals in Isfahan city. In
      addition, the incidence ratio of men to women was more than the previous studies.

PMID- 30186554
TI  - Effectiveness and safety of omega-3 fatty acids for the prevention of ischemic
      complications following carotid artery stenting: An early terminated pilot study.
AB  - Background: We aimed to study the possible beneficial effects of omega-3
      polyunsaturated fatty acids (PUFAs) in carotid artery stenting (CAS) procedure
      for decreasing post-procedural ischemic complications. Although previous evidence
      demonstrated that omega-3 PUFAs, present in fish oil, can significantly enhance
      platelet response to antiplatelet agents after percutaneous coronary intervention
      (PCI), it is unknown whether they can be used in patients undergoing CAS.
      Methods: The single-blind, case-control, pilot randomized trial study was planned
      to perform on 60 patients undergoing CAS (30 in case and 30 in control group).
      Patients in both groups were pretreated with dual antiplatelet therapy (aspirin
      80 mg/day with a loading dose of 325 mg, and clopidogrel 75 mg/day after a
      loading dose of 600 mg) at least 48 hours before the CAS. 30 patients randomly
      received 3000 mg loading dose of omega-3 fatty acids 12 hours before the
      procedure and 1000 mg omega-3 capsule the day after the procedure. All subjects
      were planned to be visited by neurologist for any peri- and post-procedural
      complications immediately after the procedure and on first, seventh, and
      thirtieth days. Results: We ended the study after the enrollment of 18 patients
      because of an unexpected hemorrhagic transformation in case group. Two patients
      in this group developed hemorrhagic symptoms less than 12 hours after the
      procedure. One of the failures occurred in a patient with small vessel disease.
      Except these two cases, no one showed any neurological deficit symptoms in both
      groups. Conclusion: In patients already receiving dual antiplatelet treatment
      before CAS, adding omega-3 PUFAs would increase the incidence of hemorrhagic
      transformation.

PMID- 30186555
TI  - Normative data for the Pyramids and Palm Trees Test in literate Persian adults.
AB  - Background: Semantic test of Pyramids and Palm Trees (PPT) is the most common
      test for assessing memory. Since this test is related to language and culture,
      normative data in different populations are needed. Methods: This study was
      conducted on 270 literate men and women Persian adults aged from 20 to 69 years.
      Subjects must select a picture or word between two pictures or words that was
      closer to target. Results: The word score was significantly positively correlated
      with the picture score (r = 0.508, P < 0.001). Word scores (median = 50, Q1-Q3 =
      49-51) were higher than the picture scores (median = 50, Q1-Q3 = 48-51), although
      the difference was small (P < 0.001). Conclusion: Demographic variables such as
      age, gender, and level of education were not significant predictors for both
      versions in Persian population.

PMID- 30186556
TI  - Transdifferentiation of human adipose-derived mesenchymal stem cells into
      oligodendrocyte progenitor cells.
AB  - Background: Stem cell-based therapy is a new method for the treatment of
      neurodegenerative diseases such as multiple sclerosis (MS). Human adipose-derived
      stem cells (hADSCs) are a kind of adult stem cells which have a higher frequency
      in the fat tissue and have the ability to differentiate into other cell types
      outside their lineage. Due to some serious adverse events of cell-based therapy
      such as tumorigenic potential, the aim of this study was to evaluate of hADSCs
      differentiation into oligodendrocytes as a valuable way for future cell
      transplantation. Methods: hADSC were isolated from lipoaspirate samples of human
      abdominal fat. After hADSC characterization via flow cytometry, the cells were
      induced to oligodendrocytes using a special differentiation medium. Finally, 3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT),
      immunocytochemistry, and real-time polymerase chain reaction (RT-PCR) techniques
      were used for the evaluation of differentiated cells. Results: Flow cytometry
      indicated that hADSCs were CD105- and CD49-positive, but were negative for CD31
      and CD45 markers. In addition, immunocytochemistry analysis revealed that a high
      percent of differentiated cells expressed oligodendrocyte progenitor cells
      markers [A2B5 and oligodendrocyte transcription factor (Olig2)] which were
      significantly higher than myelin basic protein (MBP) which is mature
      oligodendrocytes marker. Moreover, a very low percentage of differentiated cells
      expressed glial fibrillary acidic protein (GFAP) marker. Finally, real-time
      reverse transcription PCR analysis confirmed the results of immunocytochemistry.
      Conclusion: Since hADSCs have the potential to differentiate into multi-lineage
      cells and due to their additional characteristics such as immunomodulatory and
      neuroprotective properties, it seems that these cells may be an ideal cell source
      for oligodendrocytes differentiation.

PMID- 30186557
TI  - Prognostic factors in patients with acute ischemic stroke treated with
      intravenous tissue plasminogen activator: The first study among Iranian patients.
AB  - Background: Tissue plasminogen activator (tPA) has been long approved as an
      efficacious treatment in patients with acute ischemic stroke (AIS); however, due
      to some serious complications, particularly intracranial hemorrhage (ICH), many
      physicians are still reluctant to use it liberally. This study sought to find
      potential prognostic factors in patients with AIS treated with tPA. Methods: A
      retrospective, hospital-bases observational study was conducted. Consecutively, a
      total of 132 patients with AIS treated with intravenous tPA, form June 2011 to
      July 2015 were enrolled. Inclusion and exclusion criteria were based on updated
      guidelines. Probable prognostic variables were examined separately in three
      distinct groups; the occurrence of ICH within 24 hours after treatment, poor 3
      month outcome on the basis of modified Rankin Scale (mRS) and 3-month mortality.
      Results: Patients were 83 men (62.9%) and 49 women (37.1%) with a median age of
      66 years [interquartile range (IQR)of 55-72]. Any type of hemorrhage, symptomatic
      hemorrhage [based on the European Cooperative Acute Stroke Study III (ECASS III)
      definition] within 24 hours posttreatment, poor 3-month outcome (mRS 3-6), and 3
      month mortality were documented in 10.6%, 4.5%, 53.2%, and 23.6% of patients,
      respectively. Increased baseline blood glucose was a significant but dependent
      predictor of hemorrhage within the first 24 hours posttreatment. Dependent
      predictors of a 3-month poor outcome were high age, the National Institutes of
      Health Stroke Scale (NIHSS) at baseline, decreased admitting glomerular
      filtration rate (GFR), and the presence of atrial fibrillation (AF) rhythm, and
      ICH within 24 hours posttreatment. Only age [Odds ratio (OR) adjusted 1.05] and
      initial NIHSS (OR adjusted 1.23), however, were recognized as the independent
      variables in this regard. The only independent predictor of 3-month mortality was
      the initial NIHSS (OR adjusted 1.18). Conclusion: According to the findings of
      the present study, advanced age and high baseline NIHSS are two independent
      prognostic factors in patients with AIS treated with tPA.

PMID- 30186558
TI  - The effect of premorbid features on post-stroke rehabilitation outcome.
AB  - Background: A wide variety of factors influence stroke prognosis, including age,
      stroke severity, stroke mechanism, infarct location, comorbid conditions,
      clinical findings, and related complications. The aim of this study was to detect
      the prognostic determinants in patients with acute stroke for guiding
      rehabilitation. Methods: Patients with ischemic acute stroke were included in the
      study. Patients' age, sex, education level, and marital status, premorbid
      personality traits, comorbidities such as current smoking status and alcohol
      consumption, regular exercise habits, and sleeping disorder were recorded. Motor
      assessment and daily activity skills were evaluated according to the Brunnstrom
      staging and Functional Independence Measure (FIM), respectively. Results: A total
      of 85 patients were studied. All patients' motor and functional stages were
      significantly improved with the rehabilitation. The improvements in the upper
      extremity motor levels were less in whom over 76 years and smokers, in patients
      who had 4 and more comorbidities and sleep disorders. The functional improvement
      was less in whom over 76 years and men, and in patients who had 4 and more
      comorbidities and sleep disorders. Conclusion: The significant post-stroke
      predictor of insufficiency in functioning was having 4 or more risk factors.

PMID- 30186559
TI  - Predicting 30-day mortality in patients with primary intracerebral hemorrhage:
      Evaluation of the value of intracerebral hemorrhage and modified new
      intracerebral hemorrhage scores.
AB  - Background: Different criteria have been proposed to determine the mortality rate
      of primary intracerebral hemorrhage (ICH). This study aimed to evaluate ICH and
      Modified New ICH scores in predicting 30-day mortality in patients with primary
      ICH. Methods: In this prospective cohort study, 107 patients diagnosed with
      primary ICH were enrolled at an interval of six months (October 2015-March 2016).
      They were evaluated using Modified New ICH and ICH scores. The Modified New ICH
      score was different from the New ICH score since the National Institute of Health
      Stroke Scale (NIHSS) variables were replaced by Modified Rankin Scale (MRS) in
      the modified score. Results: A total of 61 patients (57%) died, and 46 (43%)
      survived during the 30-day hospitalization. ICH >= 2 and Modified New ICH >= 3
      scores predicted 30-day mortality rate in patients with the sensitivity and
      specificity rates of 87 and 63 percent, and 88 and 53 percent, respectively.
      Conclusion: The current study showed that both ICH and Modified New ICH scores
      were almost equally effective in determining the mortality rate in patients with
      primary ICH, and both criteria had acceptable value in determining the mortality
      rate of patients. Therefore, routine assessment of ICH and Modified New ICH
      scores in patients with ICH in emergency wards is recommended.

PMID- 30186560
TI  - A bibliometric study of the movement disorder field by analyzing classic citation
      data on publication.
AB  - Background: The extent to which a publication attracts scientific attention by
      virtue of its focus, provides clues about the trend and volume of scientific
      production in a particular field. Bibliometric analysis is a method to quantify
      aspects of a specific research area. This article focused on publication on the
      movement disorders. Methods: The bibliometric data on movement disorder were
      retrieved in relation to set of keywords from the Thomson Reuters Web of Science
      (WOS) available by January 2017. As many bibliometric statistics, such as
      citation indexes change during time, it was decided to compare two successive 5
      years periods, 2007-2011 and 2012-2016. In addition, the citation classics
      publications with more than 100 times cited were taken into consideration.
      Results: In total, the number of movement disorder papers rose from 49,444 to
      61,942. Clinical neurology was the most studied WOS subfield at 35.6%. About
      12.0% of these studies were published by the Movement Disorders Journal. Original
      papers accounted for 63.7% of publications. The United States of America was the
      leading country as the source of these publications followed by China. University
      College London (UCL) was associated more than any other university regarding
      these publications whereas the National Institute of Health (NIH) was the major
      source of funding. The number of papers with more than 100 citations totaled 87,
      out of which only one paper had more than 400 citations. Conclusion: This study
      demonstrates that the total number of publications in movement disorders has
      increased remarkably during the past decade.

PMID- 30186561
TI  - Ataxia and developmental delay as the main manifestation of
      rhombencephalosynapsis.

PMID- 30186562
TI  - Epidemiological burden of Listeria monocytogenes in Iran.
AB  - Objectives: Listeria monocytogenes is a foodborne pathogenic bacteria causing the
      infection listeriosis, which possibly affects all people, particularly
      immunocompromised persons and pregnant women. This microorganism can be found in
      several processed foods, dairy products, raw milk, meat and fish products,
      seafoods, eggs, fruits, and vegetables. This review discusses about the
      epidemiological significance, incidence, contamination routes of L. monocytogenes
      in different products and current data about listeriosis in the Iran. Materials
      and Methods: For accessing to relevant articles and studies, a search was done in
      main databases and also, almost all Iranian published articles were studied in
      this field. Results: Outbreaks of listeriosis have been reported in many parts of
      the worldwide, however there is scanty data about the prevalence of listeriosis
      in Iran. Accordingly, as a result of high incidence of L. monocytogenes in women
      with bad obstetric history or history of abortions, diagnosis procedures for
      detection of L. monocytogenes and timely treatment was suggested. Conclusion: In
      spite of low incidence of infection in the past, increased interest for lightly
      preserved and/or ready-to-eat (RTE) food products has recently led to increasing
      of L. monocytogenes prevalence which has become a public health concern.
      Subsequently, further researches about the prevalence of L. monocytogenes and
      also antibiotic susceptibility testing is needed to enable the detection of the
      contaminated foods, as well as ensures the effective treatment.

PMID- 30186564
TI  - Antioxidant role of melatonin against nicotine's teratogenic effects on embryonic
      bone development.
AB  - Objectives: This study investigated the possible effects of low (3 mg/kg) and
      high (6 mg/kg) doses of nicotine on the skeletal development of rat fetuses by
      the double staining method and the protective role of melatonin (10 mg/kg)
      against these effects. Materials and Methods: Eighteen adult female Wistar-Albino
      rats were divided into six groups (n=3, each) as control, low-dose nicotine, high
      dose nicotine, low-dose nicotine+melatonin, high-dose nicotine + melatonin and
      melatonin. While nicotine was given to the experimental groups on gestation days
      1-20, nicotine and melatonin were administered together to the treatment groups.
      The fetuses were delivered by cesarean section on the 20th day of pregnancy. The
      skeletal systems of the fetuses were stained using the double staining method.
      The forelimbs and hindlimbs of the fetuses were firstly investigated under a
      stereomicroscope, and then their photos were taken. The total bone length, the
      length of the ossified part and the ossification rate were calculated using the
      ImageJ program. Results: The degree of ossification in the bones of the feet and
      the hands was determined. When the total bone length and the length of the
      ossified part were evaluated, they were significantly decreased in the nicotine
      groups (P<0.05), but were close to each other in the treatment and the control
      groups (P<0.05). Conclusion: It has been found that the use of nicotine during
      pregnancy delays skeletal ossification and that melatonin, a powerful
      antioxidant, eliminates the teratogenic effects of nicotine.

PMID- 30186565
TI  - Cytotoxic effect of pyocyanin on human pancreatic cancer cell line (Panc-1).
AB  - Objectives: Pyocyanin, a blue-green pigment produced by Pseudomonas aeruginosa,
      interferes with host redox cycles, which can lead to generation of reactive
      oxygen species and progressive cellular oxidative damage. The aim of this study
      was to assess the influence of pyocyanin on human pancreatic cancer cell line.
      Materials and Methods: Polymerase Chain Reaction (PCR) was applied to confirm the
      existence of a specific pyocyanin producing gene (phzM). The pigment was then
      characterized by UV-visible, FT-IR, and HPLC analysis. Panc-1 cells were treated
      by different concentrations of pyocyanin and their cytotoxic effect as well as
      the induction of apoptosis/necrosis were evaluated by XTT assay and flow
      cytometry. Results: An overnight pyocyanin treatment resulted in significant cell
      reduction in a concentration-dependent manner. Inhibition rate of 6 mg.ml-1
      pyocyanin (the highest concentration) extracted from clinical and soil isolates
      of P. aeruginosa were 98.69+/-0.23 and 89.88+/-1.86%, respectively, which
      decreased as the pyocyanin concentration lessened. Pyocyanin could also induce
      dose-dependent apoptosis/necrosis in Panc-1 cells after 24 hr. Conclusion: We
      reported, for the first time, cytotoxic effects of pyocyanin against human
      pancreatic cancer cell line. Considering this effect of the pigment, study on
      pyocyanin as a potential anti-tumor biodrug requires further studies.

PMID- 30186563
TI  - Effects of troxerutin on anxiety- and depressive-like behaviors induced by
      chronic mild stress in adult male rats.
AB  - Objectives: Chronic stress has been linked to the pathophysiology of mood
      disorders including anxiety and depression. In this study, we aimed to
      investigate the effect of troxerutin (TRX), as a flavonol, on stress-induced
      anxiety and depression. Materials and Methods: 56 animals were randomly divided
      into seven groups (n=8 per group) as follows: control, saline, TRX 50, TRX 150,
      TRX 300, Diazepam, and Imipramine. Chronic mild stress (CMS) was induced by
      restraining animals in Plexiglas cylinders for 1 hr each day for 25 consecutive
      days. Different doses (50, 150, and 300 mg/kg, oral gavage) of troxerutin was
      gavaged for 14 consecutive days. At the end of treatments, anxiety- and
      depressive-like behaviors were tested using elevated plus-maze (EPM), open field
      test (OFT), and forced swimming test (FST). Results: CMS significantly increased
      immobility (P<0.05) and decreased swimming (P<0.01) time in FST. However,
      different doses of troxerutin significantly decreased immobility (P<0.01) and
      increased swimming (P<0.001) time. CMS also significantly (P<0.01) decreased the
      percentage of open arm entrance (%OAE), whereas troxerutin significantly
      increased both %OAE and percentage of open arm time (%OAT) in the EPM. Moreover,
      CMS significantly decreased time spent in the center (P<0.001) and the number of
      center entrances (P<0.01) in the OFT. However, troxerutin significantly increased
      time spent in the center and number of the entrances crossing. Furthermore, CMS
      significantly increased serum cortisol levels and troxerutin decreased it.
      Conclusion: Troxerutin demonstrated anxiolytic- and antidepressant-like
      activities in rodents, which supports the use of herbal medicine in the mood
      disorders.

PMID- 30186566
TI  - The effects of mid- and long-term endurance exercise on heart angiogenesis and
      oxidative stress.
AB  - Objectives: Long-term, irregular endurance exercise may result in disturbance to
      the angiogenesis of heart muscles and blood supply. The aim of the present study
      is to evaluate the effects of mid- and long-term endurance exercise on the
      process of angiogenesis. Materials and Methods: Eighteen male Wister rats of
      220+/-10 g, were randomly assigned to three groups of 6 rats including: Control,
      Mid, and Long Group. After the training sessions, the rats were weighed and
      sacrificed. Results: In comparison to the Control Group, the both groups,
      indicated remarkable increase in the weight of heart and significantly higher
      serum LDH and CK activity (P<0.01). In addition, after the training sessions,
      weakened antioxidant heart system (TAC, total thiol groups, and GPX activity) and
      increased oxidative stress markers (MDA and NO) were remarkably observed in Mid
      Group and particularly in those in the Long Group in comparison to the Control
      Group (P<0.05). Finally, significant increase in VEGF-B, MEF-2C and MMP-2 gene
      expression was found for both experimental groups, associated with the up
      regulation of ANGPT-1 and HDAC4 in the Mid Group (P<0.05). While the longer
      exercise period induced significantly upper VEGF-B, MEF-2C, and MMP-2 and
      significantly lower ANGPT-1 and HDAC4 in the Long Group (P<0.05). Conclusion: In
      this study, higher oxidative status and upper angiogenic gene expression with
      higher VEGF-B, MEF-2c, and MMP-2 and lower ANGPT-1 and HDAC4 were traced as
      effects of long-term endurance exercise. These results point to the dis
      regulation of blood supply in the presence of angiogenesis resulting from long
      term exercise.

PMID- 30186568
TI  - ADAM33 gene polymorphisms in Southwestern Iranian patients with asthma.
AB  - Objectives: Asthma, the most frequent chronic respiratory disease, results from a
      complex interaction between multiple genes and environmental factors. To date,
      more than 100 candidate genes and single nucleotide polymorphisms (SNPs) have
      been reported to be associated with asthma. One of the discovered genes related
      to asthma is ADAM33. However, the relationship between ADAM33 gene polymorphisms
      and asthma is controversial. The aim of this study was to investigate the
      association between four ADAM33 gene SNPs and susceptibility to asthma in
      patients from southwestern Iran. Materials and Methods: ADAM33 gene polymorphisms
      at positions T+1 (rs2280091), T1 (rs3918396), S1 (rs2280089), and F+1 (rs511898)
      were examined in 150 patients with asthma and 149 age- and sex-matched healthy
      controls with a PCR-RFLP method. Results: There were no differences between
      patients and controls in allelic or genotype frequencies of ADAM33 SNPs. We found
      no associations between allelic or genotype distribution of the SNPs and
      spirometry indices, concomitant involvement of other allergic diseases, or
      exposure to cigarette smoke. In contrast to H4 haplotype, which appeared to be
      protective against asthma, inheritance of H2 and H3 haplotypes increased the risk
      of asthma up to 2-3 folds. Conclusion: ADAM33 gene polymorphisms appear to play a
      partial role in asthma susceptibility, investigation of expression changes in
      this gene in response to environmental factors or the local formation of a
      soluble form of the molecule in the lung can be helpful to elucidate the impact
      of this molecule in the induction of asthma.

PMID- 30186569
TI  - Exercise training has restorative potential on myocardial energy metabolism in
      rats with chronic heart failure.
AB  - Objectives: Exercise training is a well-known accelerator for the treatment of
      chronic heart failure (CHF). The current study aimed to investigate the
      restorative effects of aerobic interval training (AIT) intervention on myocardial
      energy metabolism in CHF rats. Materials and Methods: Post-myocardial infarction
      (MI) heart failure animal model was established. The Sprague-Dawley rats were
      randomly divided into sham operation group (Sham group), CHF model group, and CHF
      exercise group (Exercise-CHF group). Results: Our data showed that when compared
      to the Sham group, the left ventricular systolic pressure (LVSP), myocardial
      glycogen content, and expression levels of key components of AMP-activated
      protein kinase (AMPK) pathway were decreased significantly (P<0.05) in the CHF
      model group, while the left ventricular end diastolic pressure (LVEDP), fatty
      acid (FA) concentration, lactic acid content, and AMPKalpha phosphorylation (p
      AMPKalpha) were increased significantly (P<0.05) in the CHF-model group.
      Importantly, AIT reversed these alterations induced by post-MI. Conclusion:
      Findings of this study demonstrated that AIT could improve the metabolic
      remodeling and enhance cardiac function, which may be associated with the
      activation of AMPK/ peroxisome proliferator activated receptor alpha (PPARalpha)
      and its downstream signaling pathway.

PMID- 30186567
TI  - Wear particles enhance autophagy through up-regulation of CD147 to promote
      osteoclastogenesis.
AB  - Objectives: The study aimed to uncover the underlying mechanism linking wear
      particles to osteoclast differentiation, and we explored the effect of titanium
      particles of different sizes on CD147 expression and autophagy in macrophages.
      Materials and Methods: Effects of titanium particles on CD147 and RANKL mRNA were
      detected by QPCR; protein level of CD147 and Beclin-1 were detected by Western
      blot; soluble RANKL were detected by ELISA. To determine the effect of CD147 and
      autophagy, KG-1a cells were transfected with siRNA-CD147 or treated with
      autophagy inhibitor CQ (chloroquine), and then co-cultured with different sizes
      of titanium particles. Results: Our results showed that 0.2-1.2 um and 1.2-10 um
      titanium particles up-regulate CD147 to activate autophagy, which increase the
      level of soluble RANKL to promote osteoclastogenesis. Suppression of CD147 with
      siRNA could diminish particle-induced autophagy and soluble RANKL expression. In
      addition, CQ could dramatically reduce particle-induced soluble RANKL expression.
      Conclusion: Our findings suggested a possible mechanism underlying wear debris
      induced osteolysis and identified CD147 as a potential therapeutic target in
      aseptic loosening.

PMID- 30186570
TI  - In vivo effects of allogeneic mesenchymal stem cells in a rat model of acute
      ischemic kidney injury.
AB  - Objectives: Renal ischemia-reperfusion injury (IRI) as a severe condition of
      acute kidney injury (AKI) is the most common clinical problem with high mortality
      rates of 35-60% deaths in hospital. Mesenchymal stem cells (MSC) due to unique
      regenerative characteristics are ideal candidates for the treatment of the
      ischemic injuries. This work is focused on the administration of MSC to IRI
      induced AKI Wistar rats and evaluating their significance in AKI treatment.
      Material and Methods: Animals underwent surgical procedure and AKI was induced by
      40 min bilateral renal pedicle clamping. Immediately after reperfusion, 2*106 rat
      bone marrow derived MSCs were injected via intra-parenchymal or intra-aortic
      route. Results: Animals subjected to AKI after days 1 and 3 showed significant
      increase in the serum creatinine and blood urea nitrogen (BUN) concentration
      along with a declined glomerular filtration rate (GFR) when compared with non
      ischemic animals. On the other hand, treated animals showed a significant
      enhanced regeneration as compared to ischemic animals in both administration
      route groups. Conclusion: According to the results concluded from the
      renoprotective effects of MSC in IRI/AKI, MSCs could be considered as promising
      therapeutic approach for AKI in clinical applications.

PMID- 30186572
TI  - Oral administration of alanyl-glutamine and glutamine improve random pattern
      dorsal skin flap survival in rats.
AB  - Objectives: Skin flap necrosis is the most common postoperative side effect in
      reconstructive surgeries. Glutamine (GLN) has been shown to accelerate wound
      healing process. The purpose of this study was to evaluate the effects of GLN
      either in free form or in the dipeptide form along with L- alanyl (Ala-GLN) on
      random skin flaps survival in rats. Materials and Methods: Dorsal skin flaps with
      caudal bases (8 *2 cm) were established in 24 adult male Wistar rats. Then, the
      animals were randomly assigned into 3 groups (n=8). Control, GLN (0.75 g/kg) and
      Ala-GLN (0.75 g/kg). All groups administrated orally 24 and 6 hr before flap
      elevation and continued repeatedly daily until 7 days postoperation. The flap
      survival rate and vascular density using histological analysis were evaluated.
      Vascular endothelial growth factor (VEGF) by immunohistochemical method was
      determined. Results: Seven days after surgery, the mean surviving area in the GLN
      and Ala-GLN groups were significantly greater than in the untreated control group
      (P<0.001). Furthermore, in comparison with the control group, the number of blood
      vessels and VEGF-positive cells in treated groups with GLN and Ala-GLN were
      significantly higher. However, no significant differences were observed between
      treated groups with GLN and Ala-GLN. Conclusion: The findings from this study
      indicate that oral administration of GLN in free form or in the dipeptide (Ala
      GLN) could promote neovascularization and improve skin flap survival in rats.

PMID- 30186571
TI  - iTRAQ-based proteomics profiling of Schwann cells before and after peripheral
      nerve injury.
AB  - Objectives: Schwann cells (SCs) have a wide range of applications as seed cells
      in the treatment of nerve injury during transplantation. However, there has been
      no report yet on kinds of proteomics changes that occur in Schwann cells before
      and after peripheral nerve injury. Materials and Methods: Activated Schwann cells
      (ASCs) and normal Schwann cells (NSCs) were obtained from adult Wistar rat
      sciatic nerves. After immunofluorescence identification, we identified
      differentially expressed proteins in the ASCs and NSCs using isobaric tags for
      relative and absolute quantitation (iTRAQ) combined with high-resolution Orbitrap
      liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). In
      addition, all the differentially expressed proteins were analyzed by Gene
      ontology (GO) analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway
      analysis. Finally, several differentially expressed proteins were selected for
      Western blot verification. Results: A total of 122 differentially expressed
      proteins in ASCs and NSCs were screened. GO analysis suggested that these
      different proteins are likely to accumulate in the cytoplasm and are associated
      with single-multicellular organism processes. The KEGG pathway analysis suggested
      that proteins related to purine metabolism were significantly enriched. The
      expression of Transmembrane glycoprotein NMB (GPNMB), Ectonucleotide
      pyrophosphatase/phosphodiesterase family member 3 (ENPP3), and other proteins
      were consistent with the proteomics data obtained by Western blot analysis.
      Conclusion: GPNMB, ENPP3, GFPT2, and other proteins may play an important role in
      the repair of peripheral nerve injury. This study may provide new insights into
      changes in SCs after peripheral nerve injury.

PMID- 30186574
TI  - Angiotensin II type 1 receptor blocker losartan attenuates locomotor, anxiety
      like behavior, and passive avoidance learning deficits in a sub-chronic stress
      model.
AB  - Objectives: Stress alters sensory and cognitive function in humans and animals.
      Angiotensin (AT) receptors have demonstrated well-established interactions in
      sets of physiological phenomena. AT1 receptors can play a part in stress-induced
      activation of hypothalamic-pituitary-adrenal (HPA) axis; besides angiotensinergic
      neurotransmission plays a pivotal role in stress-evoked physiological responses.
      AT1 receptors are also involved in nociception and memory. The objective of the
      current study was to evaluate the effects of losartan as an AT1R antagonist in
      locomotor activity, nociception and memory impairments induced by sub-chronic
      swim stress. Materials and Methods: A two-session forced swimming stress protocol
      was administered to the rats. Pretreatment with losartan (10 mg/kg, IP) or saline
      was made before each swimming session. Locomotor activity, anxiety-like behavior,
      nociception, and passive avoidance learning were evaluated 24 hr after last swim
      stress session. Results: Swim stress induced increased anxiety-like behavior in
      the open field test, which pretreatment with losartan did counterbalance.
      Increased thermal threshold was observed in the nociceptive measurement after
      swim stress. Pretreatment with losartan attenuated the increased threshold and
      also inhibited a decreased step-through latency that was observed in the memory
      paradigm after swim stress. Conclusion: The results of this study indicate that
      sub-chronic swim stress impairs passive avoidance learning, anxiety-like
      behaviors, and nociception; and AT1 receptor seems to have a modulatory role in
      these alterations. However, further studies are suggested to examine the
      protective effect of AT1R inhibitors on stress-induced impairments in sensory and
      cognitive function.

PMID- 30186573
TI  - Di-(2-ethylhexyl) phthalate induces precocious puberty in adolescent female rats.
AB  - Objectives: Nowadays, Di-(2-ethylhexyl) phthalate (DEHP) is widely used in
      different kinds of commercial products as a plasticizer. Previous studies have
      revealed that exposures to DEHP could be associated with precocious puberty in
      teenagers, but the exact mechanism is yet to be known. Materials and Methods: In
      this study, 48 prepubertal Wistar female rats were randomly apportioned into 4
      groups and orally treated with 0, 250, 500, and 1000 mg/kg/d DEHP from postnatal
      day 21 up to 4 weeks. Subsequently, we examined the indicators related to the
      initiation of sexual development. Results: DEHP was able to shorten the vaginal
      opening time and prolong the estrous cycles of female rats. IGF-1 expression was
      significantly upregulated by 1000 mg/kg/d DEHP in the hypothalamus, and the
      hypothalamic, as well as serum levels of GH, were also upregulated by DEHP. It
      also caused decrements in serum levels of FSH, LH, and T and the increment in
      level of progesterone. Meanwhile, DEHP was able to exert its effect on the mRNA
      and protein expression levels of Kiss-1, GPR54, and GnRH in the hypothalamus in
      pubertal female rats. Conclusion: These findings are revealing that DEHP exposure
      more likely causes imbalances of hypothalamus functioning in pubertal female rats
      and thus induces precautious puberty in these animals.

PMID- 30186576
TI  - In vitro kinetics and inhibition of krait snake's venom acetylcholinesterase by
      Calligonum polygonoides extract in relation to the treatment of Alzheimer's
      disease.
AB  - Objectives: The objective of this study was to evaluate pharmacological effect of
      Calligonum polygonoides against Krait snake's venom acetylcholinesterase (AChE)
      and to extent it for the treatment of Alzheimer's disease. Materials and Methods:
      Acetylcholinesterase activity was measured using Ellman method with some
      modification. The kinetic studies of methanolic extract of C. polygonoides
      against krait (Bungarus Sindanus) snake venom AChE was measured with the help of
      the Lineweaver Burk double reciprocal plot. Results: Statistical data of the
      results showed that C. polygonoides extract inhibited the krait venom AChE in
      concentration dependent manner. Kinetic analysis using Line weaver Burk plot
      revealed that C. polygonoides caused mixed type of inhibition i.e. km value
      increased (25-106.6%) while Vmax decreased from 15 to 50% with an increase of C.
      polygonoides extract concentrations (100-300 ug/ml). The calculated IC50 value of
      C. polygonoides was found to be 250 ug/ml. Conclusion: C. polygonoides extract
      can be considered as a therapeutic agent to cure Alzheimer's disease via
      inhibition of AChE activity to increase the level of acetylcholine in the body
      system.

PMID- 30186575
TI  - Hypoxia-reoxygenation induced necroptosis in cultured rat renal tubular
      epithelial cell line.
AB  - Objectives: The aim of this study is to explore the potential role of
      hypoxia/reoxygenation in necroptosis in cultured rat renal tubular epithelial
      cell line NRK-52E, and further to investigate its possible mechanisms. Materials
      and Methods: Cells were cultured under different hypoxia-reoxygenation conditions
      in vitro. MTT assay was used to measure the cell proliferation of cells that were
      exposed to hypoxia-reoxygenation conditions at different time points. Receptor
      interacting protein 1,3 (RIP1 and RIP3) and NF-kappaB were detected by Western
      blot analysis. Co-immunoprecipitation (Co-IP) was conducted to investigate the
      formation of necrosome. Necrostatin-1 (Nec-1) was adopted to inhibit the
      occurrence of necroptosis. In addition, morphological changes of cells after
      hypoxia-reoxygenation interference were observed under transmission electron
      microscope (TEM). Results: MTT assay indicated that hypoxia-reoxygenation
      treatment can cause a decrease in cell viability. Particularly, 6 hr of hypoxia
      and 24 hr of reoxygenation (H6R24 group) resulted in the lowest cell viability.
      Western-blot results indicated that the expression of RIP3 significantly
      increased in H6R24 group while the expression of NF-kappaB is decreased. Co-IP
      results demonstrated that the interaction between RIP1 and RIP3 was stronger in
      the hypoxia-reoxygenation induced group than the other groups, furthermore,
      treatment with Nec-1 reduced the formation of necrosome. TEM observation results
      showed that hypoxia-reoxygenation treated cells showed typical morphological
      characteristics of necroptosis and autophagy. Conclusion: Hypoxia-reoxygenation
      treatment can induce necroptosis in NRK-52E cells, and this effect can be
      inhibited by Nec-1. In addition, the mechanism of necroptosis induced by hypoxia
      reoxygenation injury on cells may be related to the low expression of NF-kappaB.

PMID- 30186579
TI  - Sixteen Years of Experience with the Treatment of Advanced Colorectal Cancer in
      Iran; A Report from Three Institutions.
AB  - BACKGROUND Colorectal cancer (CRC) is one of the most common cancers worldwide.
      Recently treatments of advanced CRC have been immensely improved. In this study
      we reported the current state of advanced CRC in Iran regarding treatment and
      outcomes from 2000 to 2016. METHODS 370 subjects with stage III or IV of the
      disease were included in this study. Pathological subtypes other than
      adenocarcinoma were excluded. Demographics and other relevant clinical data were
      collected. RESULTS Mean age at diagnosis was 55.4 +/- 12.6 years. Significant
      differences regarding the age, sex, primary tumor complication and location,
      lymph node involvement, and tumor size were not detected between patients with
      stage III and IV. Overall survival rate at 5 years was 69.5% (95% confidence
      interval: 60.8% - 76.6%) and 21.73% (95% CI: 12.46% - 32.70%) for patients with
      stage III and IV, respectively. Analysis of prognostic factors revealed that
      tumor grade was an independent factor predicting poorer outcome (poorly
      differentiated vs. well or moderately differentiated). Furthermore, in stage IV
      of the disease, IVb subgroup was found to be associated with a poorer outcome
      compared with stage IVa. CONCLUSION Even with the acceptable survival rates and
      more effective treatments, it seems that clinicopathological characteristics have
      yet the most important prognostic effect in advanced CRC.

PMID- 30186578
TI  - A Comprehensive Look at Irritable Bowel Syndrome and its Associated Factors
      Considering the Rome IV Criteria: A Penalized Smoothly Clipped Absolute Deviation
      Regression Approach in the Pars Cohort Study.
AB  - BACKGROUND After the introduction of the Rome IV criteria for the diagnosis of
      irritable bowel syndrome (IBS), studies on the clinical significance of the new
      criteria in the settings of a large study has been scarce. Objective: Herein we
      used the infrastructures provided by one the largest cohort studies in Iran to
      evaluate the epidemiological features related to IBS. METHODS A total of 9264
      participants, were enrolled in the initial registry. Diagnosis of IBS was done
      using the Rome IV criteria. Individuals with IBS were compared with a control
      group. Since the study included a large sample size of patients, we used the
      penalized smoothly clipped absolute deviation (SCAD) regression analysis to
      construct a model for the evaluation of factors associated with IBS. RESULTS
      Overall, data of 9163 participants entered the final analysis. In total, 1067
      (11.6%) individuals were diagnosed with IBS, among which 57 (5.3%) were diarrhea
      dominant (IBS-D), 380 (35.6%) were constipation dominant (IBS-C), and 630 (59%)
      did not mention having any of the two (IBS-U). In the regression model, back
      pain/arthralgia (OR: 1.98, 95% CI: 1.65 - 2.40), insomnia (OR: 1.65, 95% CI: 1.40
      - 1.93), depression (OR: 1.64, 95% CI: 1.38 - 1.95), female sex (OR: 1.58, 95%
      CI: 1.27 - 1.96), anxiety (OR: 1.43, 95% CI: 1.21 - 1.69), and being married (OR:
      1.23, 95% CI: 1.03 - 1.48), were associated with higher rates of IBS. We found
      that IBS prevalence displays a peak at the age of 41 years for both men and
      women. CONCLUSION The present study provides a background for follow-up studies
      to be conducted in order to evaluate causality between IBS and some major
      diseases such as liver disease. We also found that opium use, although not
      statistically significant, in addition to sex, education, back/joint pain,
      depression, insomnia, anxiety, and marital status might be a contributing factor
      in IBS.

PMID- 30186580
TI  - Is There Any Evidence for a Viral Cause in Achalasia?
AB  - BACKGROUND Achalasia, as an incurable disease is defined by the lack of normal
      esophageal peristalsis and loss of lower esophageal sphincter relaxation due to
      impaired myenteric neural plexus. The exact cause of myenteric neural cells
      degeneration in achalasia is still unknown. One hypothesis is that certain
      neurotropic viruses and autoimmune factors cause the inflammatory response in
      myenteric network, which consequently destroy neural cells. This study was
      designed to find the evidence of viral causes of achalasia. METHODS In this case
      control study, 52 patients with achalasia and 50 controls referred to Shariati
      Hospital, were evaluated for the genome of neurotropic viruses, HPV, and
      adenovirus by polymerase chain reaction (PCR) and reverse transcription (RT) PCR
      techniques. RESULTS Genome assessment of neurotropic DNA viruses turned out
      negative in the patients, however, the genome of HSV-1 (Herpes simplex virus) was
      found in tissues of six controls. No neurotropic RNA viruses were observed in the
      tissue samples and whole blood of both the patients and controls. Among non
      neurotropic viruses, adenovirus genome was positive in tissues of two out of 52
      patients and three out of 50 controls. In addition, one out of 52 patients and
      two out of 50 controls were positive for HPV infection in tissues. CONCLUSION We
      could not detect any significant relationship between achalasia and HPV,
      adenovirus, and neurotropic viruses in the cases. Nevertheless, it does not
      exclude the hypothesis of either an alternate viral species or resolved viral
      infection as the etiology of achalasia.

PMID- 30186581
TI  - Nebulette Expression Is Associated with Lymph Node Metastasis in Patients with
      Colorectal Cancer.
AB  - BACKGROUND Colorectal cancer (CRC) is one of the most common cancers among men
      and women worldwide. Cancer metastasis is the main cause of death in patients
      with cancer. NEBL (nebulette, Gene ID: 10529) protein interacts with thin
      filaments in the cell and may functionally destabilize focal adhesion
      composition. There are some studies on NEBL gene expression alteration in cancer.
      In the presented study we aimed to analyze NEBL gene expression in patients with
      colorectal cancer to explore possible association of this gene with
      clinicopathological features in CRC. METHODS Sixty-seven fresh samples of
      colorectal tumors and adjacent normal tissues were collected from Iranian
      patients with CRC. Real time polymerase chain reaction was performed to measure
      the level of NEBL gene expression and its association with clinico-pathological
      features. RESULTS A significant overexpression with 3 fold increse was seen in
      NEBL mRNA level in tumoral tissues compared with the adjacent normal tissues. In
      addition there was a significant association between NEBL gene expression with
      lymph node metastasis in patients with CRC. CONCLUSION The overexpression of NEBL
      has the capacity to be considred as a prognostic biomarker in patients with CRC.

PMID- 30186577
TI  - New Concepts on Reversibility and Targeting of Liver Fibrosis; A Review Article.
AB  - Currently, liver fibrosis and its complications are regarded as critical health
      problems. With the studies showing the reversible nature of liver fibrogenesis,
      scientists have focused on understanding the underlying mechanism of this
      condition in order to develop new therapeutic strategies. Although hepatic
      stellate cells are known as the primary cells responsible for liver fibrogenesis,
      studies have shown contributing roles for other cells, pathways, and molecules in
      the development of fibrosis depending on the etiology of liver fibrosis. Hence,
      interventions could be directed in the proper way for each type of liver diseases
      to better address this complication. There are two main approaches in clinical
      reversion of liver fibrosis; eliminating the underlying insult and targeting the
      fibrosis process, which have variable clinical importance in the treatment of
      this disease. In this review, we present recent concepts in molecular pathways of
      liver fibrosis reversibility and their clinical implications.

PMID- 30186584
TI  - CT Quadrate Lobe Hot Spot Sign.

PMID- 30186583
TI  - Multiple Subcutaneous Nodules Leading to Diagnosis of Colon Cancer.
AB  - Skin metastases from colorectal carcinoma are rare and signal advanced disease.
      Skin metastasis refers to growth of cancer cells in the skin originating from an
      internal cancer. In most cases, cutaneous metastasis develops after the initial
      diagnosis of the primary internal malignancy and late in the course of the
      disease. In very rare cases, skin metastasis may occur at the same time or before
      the primary cancer has been discovered and may be the prompt for further thorough
      investigation. The incidence of skin metastasis varies but is somewhere between 3
      10% in patients with a primary malignant tumor. Most common ones are melanoma
      (45%), breast cancer (30%), nasal sinus cancers (20%), cancer of the larynx and
      cancer of the oral cavity (12%) cases. Here we present a case of 39-year-old man
      presented to us with multiple subcutaneous lesions over the chest and forehead.
      Fine needle aspiration cytology of skin nodules revealed metastatic
      adenocarcinoma features. Further imaging of the abdomen with computed tomography
      (CT) revealed circumferential narrowing of caecum and ascending colon. The
      patient was managed with palliative right hemicolectomy in view of constipation
      and palliative chemotherapy as systemic treatment. An extensive review of the
      English literature did not reveal extensive data on metastatic subcutaneous
      nodules leading to diagnosis of colon cancer.

PMID- 30186582
TI  - Socioeconomic Inequalities in Gastroesophageal Reflux Disorder: Results from an
      Iranian Cohort Study.
AB  - BACKGROUND Despite progress in the health indexes in recent years, health
      inequalities remain as a global challenge within and between regions and
      countries. This study is the first to quantify the socioeconomic inequity in
      gastroesophageal reflux disease (GERD) using the concentration index. METHODS In
      this cross-sectional study, we used baseline data (7012 subjects) from the Fasa
      Cohort Study (the Southern Iran). The principal component analysis was used to
      construct socioeconomic status of the participants. The concentration index and
      concentration curve were used to measure socioeconomic-related inequality in
      GERD. Decomposition of concentration index was also done to identify the
      contribution of each explanatory variable to the wealth-related inequality in
      GERD prevalence. RESULTS The prevalence of GERD was 16.9% (95% CI: 15.9-17.7%).
      The overall concentration index for GERD was 0.093 (95% CI: 0.062-0.166].
      Correspondingly, this figure for men and women were 0.116 (95% CI: 0.062-0.171%)
      and 0.091 (95% CI: 0.044-0.137%), respectively. The main contributors of
      socioeconomic-related inequality in GERD prevalence were socioeconomic status
      (64.4%), alcohol drinking (29%), and age (8.4%). CONCLUSION GERD is significantly
      more concentrated among richest people. There was significant socioeconomic
      inequality in GERD according to some individual factors. These inequalities need
      to be addressed by policy makers to identify the vulnerable subgroups and to
      reduce the disease burden in the community.

PMID- 30186585
TI  - The Situation of Liver Transplantation Programs in Iran.

PMID- 30186586
TI  - Mechanical Design and Control Strategy for Hip Joint Power Assisting.
AB  - The basic requirements for mechanical design and control strategy are adapting to
      human joint movements and building an interaction model between human and robot.
      In this paper, a 3-UPS parallel mechanism is adopted to realize that the
      instantaneous rotation center of the assistive system coincides with human joint
      movement center, and a force sensory system is used to detect human movement
      intention and build the modeling of control strategy based on the interactive
      force. Then, based on the constructed experimental platform, the feasibility of
      movement intention detection and power assisting are verified through the
      experimental results.

PMID- 30186588
TI  - Discovery of Interstellar Isocyanogen (CNCN): Further Evidence that
      Dicyanopolyynes are Abundant in Space.
AB  - It is thought that dicyanopolyynes could be potentially abundant interstellar
      molecules, although their lack of dipole moment makes it impossible to detect
      them through radioastronomical techniques. Recently, the simplest member of this
      chemical family, cyanogen (NCCN), was indirectly probed for the first time in
      interstellar space through the detection of its protonated form toward the dense
      clouds L483 and TMC-1. Here we present a second firm evidence of the presence of
      NCCN in interstellar space, namely the detection of the metastable and polar
      isomer isocyanogen (CNCN). This species has been identified in L483 and
      tentatively in TMC-1 by observing various rotational transitions in the lambda 3
      mm band with the IRAM 30m telescope. We derive beam-averaged column densities for
      CNCN of 1.6 * 1012 cm-2 in L483 and 9 * 1011 cm-2 in TMC-1, which imply
      fractional abundances relative to H2 in the range (5 - 9) * 10-11. While the
      presence of NCCN in interstellar clouds seems out of doubt owing to the detection
      of NCCNH+ and CNCN, putting tight constraints on its abundance is still hampered
      by the poor knowledge of the chemistry that links NCCN with NCCNH+ and especially
      with CNCN. We estimate that NCCN could be fairly abundant, in the range 10-9-10-7
      relative to H2, as other abundant nitriles like HCN and HC3N.

PMID- 30186587
TI  - Amodal Completion of a Target Template Enhances Attentional Guidance in Visual
      Search.
AB  - When searching for a target object in cluttered environments, our visual system
      appears to complete missing parts of occluded objects-a mechanism known as
      "amodal completion." This study investigated how different variants of completion
      influence visual search for an occluded target object. In two experiments,
      participants searched for a target among distractors in displays that either
      presented composite objects (notched shapes abutting an occluding square) or
      corresponding simple objects. The results showed enhanced search performance when
      composite objects were interpreted in terms of a globally completed whole. This
      search benefit for global completions was found to be dependent on the
      availability of a coherent, informative simple-object context. Overall, these
      findings suggest that attentional guidance in visual search may be based on a
      target "template" that represents a globally completed image of the occluded
      (target) object in accordance with prior experience.

PMID- 30186589
TI  - Mesenteric fibromatosis in a patient with a history of neuroblastoma: a case
      report.
AB  - Mesenteric fibromatosis (MF) is a locally aggressive proliferative spindle cell
      lesion of the mesentery. A 34-year-old male presented with increasing abdominal
      pain and constipation. On workup, patient was found to have a large pelvic mass
      on CT A/P concerning for cancer. The patient underwent surgical excision of >15
      cm intra-abdominal tumor along with adherent small bowel section. Histology of
      the tumor showed a spindle cell lesion consistent with MF. Previous reports have
      shown association of MF with Gardner syndrome and familial adenomatous polyposis.
      We present the first reported case of MF in a patient with previous
      neuroblastoma.

PMID- 30186590
TI  - Influence of Climatic Factors on Malaria Epidemic in Gulu District, Northern
      Uganda: A 10-Year Retrospective Study.
AB  - Background: Globally, 15 countries, mainly in Sub-Saharan Africa, account for 80%
      of malaria cases and 78% of malaria related deaths. In Uganda, malaria is endemic
      and the mortality and morbidity due to malaria cause significant negative impact
      on the economy. In Gulu district, malaria is the leading killer disease among
      children <5 years. In 2015, the high intensity of malaria infection in Northern
      Uganda revealed a possible link between malaria and rainfall. However, available
      information on the influence of climatic factors on malaria are scarce,
      conflicting, and highly contextualized and therefore one cannot reference such
      information to malaria control policy in Northern Uganda, thus the need for this
      study. Methods and Results: During the 10 year's retrospective study period a
      total of 2,304,537 people suffered from malaria in Gulu district. Malaria
      infection was generally stable with biannual peaks during the months of June-July
      and September-October but showed a declining trend after introduction of indoor
      residual spraying. Analysis of the departure of mean monthly malaria cases from
      the long-term mean monthly malaria cases revealed biannual seasonal outbreaks
      before and during the first year of introduction of indoor residual spraying.
      However, there were two major malaria epidemics in 2015 following discontinuation
      of indoor residual spraying in the late 2014. Children <5 years of age were
      disproportionally affected by malaria and accounted for 47.6% of the total
      malaria cases. Both rainfall (P=0.04) and relative humidity (P=0.003) had
      significant positive correlations with malaria. Meanwhile, maximum temperature
      had significant negative correlation with malaria (P=0.02) but minimum
      temperature had no correlation with malaria (P=0.29). Conclusion: Malaria in Gulu
      disproportionately affects children under 5 years and shows seasonality with a
      generally stable trend influenced by rainfall and relative humidity. However,
      indoor residual spraying is a very promising method to achieve a sustained
      malaria control in this population.

PMID- 30186591
TI  - TIPE2 acts as a biomarker for tumor aggressiveness and suppresses cell
      invasiveness in papillary thyroid cancer (PTC).
AB  - Background: Tumor necrosis factor (TNF)-alpha-induced protein 8-like 2 (TIPE2 or
      TNFAIP8L2) is a newly described negative immune regulator and is closely
      associated with various tumors. However, the expression and roles of TIPE2 in PTC
      is unknown. Results: In the present study, TIPE2 upregulation in PTC tissues was
      found to be negatively associated with tumor size, capsule infiltration,
      peripheral infiltration and tumor T stage, which could be used to predict tumor
      invasiveness. TIPE2 overexpression significantly suppressed the viability,
      proliferation, migration and invasion of PTC cells. Moreover, TIPE2 suppressed
      tumor invasiveness by inhibiting Rac1, leading to decreased expression of uPA and
      MMP9. Conclusions: These results indicate that TIPE2 is a potential biomarker for
      predicting tumor aggressiveness and suppresses tumor invasiveness in a Rac1
      dependent manner.

PMID- 30186592
TI  - Visual analogue scale for sino-nasal symptoms severity correlates with sino-nasal
      outcome test 22: paving the way for a simple outcome tool of CRS burden.
AB  - Background: A visual analogue scale (VAS) is a psychometric instrument widely
      used in the Rhinology field to subjectively quantify patient's symptoms severity.
      In allergic rhinitis, VAS has been found to correlate well with the allergic
      rhinitis and its impact on asthma severity classification, as well as with
      rhinoconjunctivitis quality of life questionnaire. In chronic rhinosinusitis
      (CRS), total VAS score are often used to classify disease burden into mild,
      moderate, and severe, with few studies correlating VAS scores with more complex
      and validated instruments assessing disease-specific burden like Sino-Nasal
      Outcome Test (SNOT)-22. Methods: We correlated VAS scores for total and
      individual sino-nasal symptom with SNOT-22 scores in a randomly selected group of
      180 CRS patients. Pearson's rho was selected as a correlation coefficient for
      analysis. Results: VAS scores for total nasal symptom score and individual
      symptoms correlated significantly with SNOT-22, irrespective of VAS based
      subclasses for sino-nasal, ocular, and bronchial symptoms. Conclusions: VAS for
      total sino-nasal symptom severity might be used for assessing disease severity,
      monitoring the course of the disease, and can be used for treatment decisions and
      disease burden.

PMID- 30186593
TI  - Manual therapy applied by general practitioners for nonspecific low back pain:
      results of the ManRuck pilot-study.
AB  - Background: Nonspecific acute low back pain (LBP) is a common reason for
      accessing primary care. German guidelines recommend non-steroidal anti
      inflammatory drugs and physical activity as evidence-based treatments. Manual
      Therapy (MT) remains controversial. To increase evidence-based treatment options
      for general practitioners (GPs), a Pilot-Study was set up to gather information
      about the required conditions and setting for an RCT. Methods: The open pilot
      study assesses recruitment methods for GPs and patients, timelines, data
      collection and outcomes of treatment immediately (T0) and 1, 6 and 12 weeks after
      consultation (T1, T2, T3). Inclusion criteria for GPs were: no experience of MT;
      for patients: adults between 18 and 50 suffering from LBP for less than 14
      days.Study process: Patients' control-group (CG) was consecutively recruited
      first and received standard care. After GPs received a single training session in
      MT lasting two and a half hours, they consecutively recruited patients with LBP
      to the intervention group (IG). These patients received add-on MT.Primary
      outcomes: (A): timelines and recruitment success, (B): assessment tools and
      sample size evaluation, (C) clinical findings: pain intensity change from
      baseline to day 3 and time till (a) analgesic use stopped and (b) 2-point pain
      reduction on an 11-point scale occurred.Secondary outcomes: functional capacity,
      referral rate, use of other therapies, sick leave, patient satisfaction. Results:
      14 GPs participated, recruiting 42 patients for the CG and 45 for the IG; 49%
      (56%) of patients were women. Average baseline pain was 5.98 points, SD: +/-2.3
      (5.98, SD +/-1.8).For an RCT an extended timeline and enhanced recruitment
      procedures are required. The assessment tools seem appropriate and provided
      relevant findings: additional MT led to faster pain reduction. IG showed reduced
      analgesic use and reduced pain at T1 and improved functional capacity by T2.
      Conclusions: Before verifying the encouraging findings that additional MT may
      lead to faster pain reduction and reduced analgesic use via an RCT, the setting,
      patients' structure, and inclusion criteria should be considered more closely.
      Trial registration: Number: DRKS00003240 Registry: German Clinical Trials
      Registry (DRKS) URL: https://www.drks.de/drks_web/. Registration date:
      14.11.2011. First patient: March 2012. Funding: the Rut and Klaus Bahlsen
      Stiftung, Hannover.

PMID- 30186595
TI  - The effects of varying class distribution on learner behavior for medicare fraud
      detection with imbalanced big data.
AB  - Healthcare in the United States is a critical aspect of most people's lives,
      particularly for the aging demographic. This rising elderly population continues
      to demand more cost-effective healthcare programs. Medicare is a vital program
      serving the needs of the elderly in the United States. The growing number of
      Medicare beneficiaries, along with the enormous volume of money in the healthcare
      industry, increases the appeal for, and risk of, fraud. In this paper, we focus
      on the detection of Medicare Part B provider fraud which involves fraudulent
      activities, such as patient abuse or neglect and billing for services not
      rendered, perpetrated by providers and other entities who have been excluded from
      participating in Federal healthcare programs. We discuss Part B data processing
      and describe a unique process for mapping fraud labels with known fraudulent
      providers. The labeled big dataset is highly imbalanced with a very limited
      number of fraud instances. In order to combat this class imbalance, we generate
      seven class distributions and assess the behavior and fraud detection performance
      of six different machine learning methods. Our results show that RF100 using a
      90:10 class distribution is the best learner with a 0.87302 AUC. Moreover,
      learner behavior with the 50:50 balanced class distribution is similar to more
      imbalanced distributions which keep more of the original data. Based on the
      performance and significance testing results, we posit that retaining more of the
      majority class information leads to better Medicare Part B fraud detection
      performance over the balanced datasets across the majority of learners.

PMID- 30186594
TI  - Depression detection from social network data using machine learning techniques.
AB  - Purpose: Social networks have been developed as a great point for its users to
      communicate with their interested friends and share their opinions, photos, and
      videos reflecting their moods, feelings and sentiments. This creates an
      opportunity to analyze social network data for user's feelings and sentiments to
      investigate their moods and attitudes when they are communicating via these
      online tools. Methods: Although diagnosis of depression using social networks
      data has picked an established position globally, there are several dimensions
      that are yet to be detected. In this study, we aim to perform depression analysis
      on Facebook data collected from an online public source. To investigate the
      effect of depression detection, we propose machine learning technique as an
      efficient and scalable method. Results: We report an implementation of the
      proposed method. We have evaluated the efficiency of our proposed method using a
      set of various psycholinguistic features. We show that our proposed method can
      significantly improve the accuracy and classification error rate. In addition,
      the result shows that in different experiments Decision Tree (DT) gives the
      highest accuracy than other ML approaches to find the depression. Conclusions:
      Machine learning techniques identify high quality solutions of mental health
      problems among Facebook users.

PMID- 30186596
TI  - Sick pets as potential reservoirs of antibiotic-resistant bacteria in Singapore.
AB  - An analysis of 186 diagnostic reports collected from a veterinary clinic in
      Singapore between 2014 to 2016 showed that sick companion animals can carry
      bacteria that are of significance to human health. Among the 186 specimens
      submitted, 82 showed polymicrobial growth (45%, 82/186) and in total, 359
      bacteria were isolated. Of the 359 bacteria reported, 45% (162/359) were multi
      drug resistant and 18% (66/359) were extended-spectrum-beta-lactamase species.
      Resistance to broad-spectrum antibiotics were also observed among individual
      species. Namely, methicillin-resistance among Staphylococcus pseudintermedius
      (63%, 32/51) and Staphylococcus aureus (50%, 4/8); fluoroquinolone-resistance
      among Escherichia coli (40%, 17/42) and carbapenem-resistance among Klebsiella
      pneumoniae (7%, 2/30) were noted. Our analysis suggests that sick pets may
      contribute to the pool of clinically relevant antibiotic-resistant bacteria and
      play a role in the spread of antibiotic resistance in Singapore. A more extensive
      study to better understand the extent of distribution and the factors affecting
      transmission of antibiotic-resistant bacteria to and from pets is necessary.

PMID- 30186598
TI  - The business of medicine and surgery with medical aid: Time for regulation and
      legislation?
AB  - The medical and surgical professions have dominated the health sciences for the
      past few centuries. As these disciplines evolve with practice, new methods,
      research, and the cost implications for both the healthcare practitioner and
      patient have increased substantially. The practice of medicine and other health
      science occupations have also evolved over the years due to the escalation of
      various diseases and mortality rates. It is however common knowledge that
      inadequate lifestyles coupled with a lack of movement; inadequate diet and
      mindsets have contributed to this debilitating epidemic we are currently plagued
      with. Due to this rapid evolvement, one cannot oversee the business involvement
      behind medicine and surgery. From one perspective, there is a majority of people
      in third world countries that cannot afford medical aid rates while the other
      shows the minority of patients that continue their treatment and live an
      inadequate lifestyle. Furthermore, one could argue that medical aid companies
      have capitalized on the notion of people affected by ill health in order to
      acquire monetary goals. The aim of this article is to showcase the business
      involvement of medicine and surgery with medical aid and to motivate the reasons
      for regulation and legislation across varied sectors. We would advocate a need to
      facilitate and streamline appropriate healthcare practice through transparency,
      patient awareness and ethical behaviours from all stakeholders involved.

PMID- 30186597
TI  - Treatment of bilateral ovarian dysgerminoma with 11-year follow-up: A case
      report.
AB  - Introduction: Malignant ovarian germ cell tumors (MOGCTs) are rare malignancies
      with an incidence of about 0.5/100,000. They account for less than 5% of all
      ovarian tumors, of which 32.8% are dysgerminomas, the female analogue of
      seminomas. These tumors occur in all age groups, with peak incidence below the
      age of 20 years in women. Aim: To describe the case of a bilateral ovarian
      dysgerminoma treatment with 11-year follow-up. Methods: Case report with details
      regarding clinical history, surgical treatment, chemotherapy and follow up. We
      include a brief literature review. Results: The patient underwent radical surgery
      for an advanced dysgerminoma, 20 cm in length, that compromised the contralateral
      ovary and sigmoid. Neoplastic cells were found in ascitic fluid. Subsequently,
      she underwent adjuvant chemotherapy according to a standard protocol. She has
      survived disease-free for more than 11 years. Conclusions: Dysgerminoma is a
      malignant neoplasm that, similar to other cancers, is easier to treat when
      diagnosed early. However, cures may be obtained even in advanced cases.

PMID- 30186599
TI  - Simultaneous resection of an adenocarcinoma of the cardia and a synchronous
      adenocarcinoma of the sigmoid: Report of a case.
AB  - Introduction: Adenocarcinoma of the cardia synchronous with other intraabdominal
      neoplasms is very rare. We report the case of a Siewert type II adenocarcinoma of
      the cardia synchronous with an adenocarcinoma of the sigmoid both treated
      simultaneously by transjatal oesophago-gastrectomy and anterior resection of the
      sigmoid. Case report: A 62 year-old male was admitted for a progressing dysphagia
      and weight loss. Oesophago-gastric fibroscopy detected an adenocarcinoma of the
      cardia extending to the distal 2 cm of the esophagus (Siewert typeII). A CT-scan
      of the chest and abdomen confirmed the cancer of the cardia and also decealed a
      synchronous tumor of the sigmoid. Both neoplasms were resected through a xipho
      pubic laparotomy, with an ileostomy completing the procedure. Postoperative
      course was uneventful and ileostomy was closed four weeks later. The patient was
      subsequently addressed to oncological for adjuvant treatment. Discussion: This
      report supports the indication of aggressive, simultaneous treatment of an
      adenocarcinoma of the cardia associated with a synchronous abdominal neoplasm,
      provided that both are resectable through the same surgical access, as
      anticipated at a preoperative, through diagnostic work-up. Conclusion:
      Simultaneous resection of synchronous adenocarcinoma of the cardia and the
      sigmoid is feasible and avoids possible progression of the untreated neoplasm
      during the interval between two separate resections, provided that a curative
      resection can be obtained for both diseases.

PMID- 30186600
TI  - Massive encrustations as a consequence of longterm indwelling urethral catheter:
      A rare case report.
AB  - Longterm indwelling urethral catheter can cause several complications such as
      lower urinary tract infections, tissue damage, pain, hemorrhage and encrustation
      of catheter leading to blockage. A 55- year old male presented with suprapubic
      pain for three months owing to poorly draining Foley catheter. He had undergone
      surgery for bladder calculi two and half a years back. He had been discharged
      with Foley catheter. He did not show up at the hospital for two and half years.
      The catheter was never changed during this period. Plain X-ray abdomen revealed a
      large encrustation with radiopacity surrounding the foley's bulb. Open suprapubic
      cystostomy was performed. The intact Foley catheter with encrusted bulb was
      removed. His postoperative period was uneventful. Surgical removal is the only
      treatment of choice for unusual massive encrustations in long-term indwelling
      urethral catheter. Minimally invasive technique is getting popularity, however we
      performed open cystostomy and removal due to the lack of expertise and
      instruments in our hospital setting. Catheterization under aseptic condition,
      frequent catheter change, early treatment of urinary infection and proper patient
      education on catheter hygiene are few methods that can reduce the complications
      of longterm indwelling urinary catheter.

PMID- 30186601
TI  - A case of excessive femoral anteversion which caused instability of the medial
      collateral ligament of the knee joint.
AB  - Introduction: The most cases of excessive femoral anteversion may be
      asymptomatic, because the he hip joint is a ball joint. However, when the hip,
      knee, or ankle joint is in a pathological state, excessive femoral anteversion
      may not be compensated for and induce symptoms. Case report: A 16-year-old female
      with achondroplasia. Medullary compression by the odontoid process caused right
      hemiplegia at 10 months after birth and equinus foot concomitantly developed. At
      14 years old, right knee pain developed during walking. For treatment, firstly,
      tenodesis of medial collateral ligament of the knee joint (MCL) was performed.
      Oblique osteotomy was applied to the proximal MCL attachment site over the distal
      tibial tuberosity, followed by simple limb lengthening, which improved knee
      instability. To prevent recurrence of knee instability, varus and
      derotationosteotomy of the femur and Vulpius procedure (triceps surae muscle
      lengthening) were additionally performed, and gait stabilized after surgery.
      Discussion: Regarding the pathogenesis, her gait was originally in-toeing because
      of excessive femoral anteversion, but the lower leg did not internally rotate
      during walking because of equinus foot, and the foot grounded in an externally
      rotated position, loading burdens on the MCL. This condition may have gradually
      caused instability of the knee over the years. Conclusion: We surgically treated
      the patient with knee joint valgus instability caused by excessive femoral
      anteversion and equinus foot and achieved a favorable outcome.

PMID- 30186602
TI  - N-carbamylglutamate restores nitric oxide synthesis and attenuates high altitude
      induced pulmonary hypertension in Holstein heifers ascended to high altitude.
AB  - Background: High-altitude pulmonary hypertension (HAPH) is a life-threating
      condition for animals in high altitude, and disturbance of endothelial nitric
      oxide (NO) synthesis contributes to its pathogenesis. N-carbamylglutamate (NCG),
      which enhances arginine synthesis, promotes endogenous synthesis of NO. In this
      study, we determined the effects of NCG on alleviating HAPH in Holstein heifers
      that ascended to Tibet (Lhasa, 3,658 m). Methods: Exp. 1, 2,000 Holstein heifers
      were transported from low elevation (1,027 m) to Lhasa. After being exposed to
      hypoxia for 1 yr, Holstein heifers were assigned to a healthy group (Control, n =
      6) with mean pulmonary hypertension (mPAP) < 41 mmHg, and an HAPH affected group
      (HAPH, n = 6) with mPAP > 49 mmHg. Lung tissues were collected to evaluate
      histopathological changes and the expression of endothelial nitric oxide synthase
      (eNOS). Exp. 2, ten healthy heifers and 10 HAPH affected heifers were
      supplemented with NCG (20 g/d per heifer) for 4 wk. Physiological parameters were
      determined and blood samples were collected on d - 1 and d 28 of the feeding
      trial. Results: Expression of eNOS in small pulmonary arteriole intima was higher
      in the healthy than HAPH group (P = 0.006), whereas HAPH group had significantly
      thicker media and adventitia than healthy group (all P < 0.05). The mRNA of eNOS
      and protein level of eNOS were higher in the lungs of heifers in the healthy
      group than in the HAPH group (both P < 0.001), whereas endothelin-1 protein
      levels were higher in HAPH group than in the healthy group (P = 0.025). NCG
      supplementation decreased mPAP and ammonia (both P = 0.001), whereas it increased
      the expression of eNOS, arginine, and plasma NO (all P < 0.05). Conclusions: The
      expression of eNOS was decreased in Holstein heifers with HAPH. NCG
      supplementation decreased mPAP through the restoration of eNOS and endogenous NO
      synthesis.

PMID- 30186603
TI  - Primary health care seeking behaviour of people with physical disabilities in
      Bangladesh: a cross-sectional study.
AB  - Background: People with disabilities constitute about 10% of the total population
      of Bangladesh. They are more likely to experience poor health than those without
      disabilities. However, there is a lack of evidence on their primary health care
      (PHC) seeking behaviour for their general illness. The aim of this study was to
      understand the PHC seeking behaviour of people with physical disabilities
      (PWPDs), and to investigate the determinants of such behaviours. Methods: We
      surveyed 282 PWPDs, aged >=18 years, using a structured questionnaire.
      Participants were recruited from the out-patient department of a rehabilitation
      centre in Dhaka between November and December 2014. We explored PHC seeking
      behaviour using frequency distribution. We performed logistic regression to
      investigate the factors that determined their PHC seeking behaviours for general
      illness. In our logistic regression model, the outcome variable was whether PWPDs
      received treatment from a formal health care provider. The predictors were socio
      demographic characteristics and clinical characteristics such as type of
      impairment and type of illness experienced. Results: Among 282 participants, 85%
      suffered from general illness in the past 6 months. The participants in the
      higher age group, for example, age group 31-45 years (OR = 3.9, [95% CI 1.2 to
      13.4]), 46-59 years (OR = 13.6, [95% CI 2.9 to 63.7) and 60+ years (OR = 12.5,
      [95% CI 1.7 to 93.0]) were more likely to seek treatment from formal health care
      providers than the age group 18-30 years. The educational attainment of the
      primary income earning family member (OR = 3.2, [CI 1.1 to 9.6]), religion (OR =
      0.3, [95% CI 0.1 to 0.98]) and mobility aid used (OR = 4.0, [95% CI 1.2 to 13])
      were determinants for seeking health care from a formal health care provider.
      Moreover, the type of illness suffered by participant was a strong predictor of
      their decision to seek treatment from a formal health care provider. The
      participants who suffered from urinary tract infections (OR = 10.3, [95% CI 2.3
      to 46.6]), ulcers (OR = 13.1, [95% CI 2.11 to 79.3]) and pain (OR = 3.6, [95% CI
      1.4 to 9.4]) were more likely to seek treatment from formal health care provider
      than who suffered from fever. Conclusions: Age, religion, earning member's
      education, type of mobility aids used and type of illness suffered were
      explicative determinants of PHC seeking behaviour of PWPDs. The results suggest
      that these factors should be considered when devising interventions for this
      population. Moreover, accessibility, quality of care and expertise of the
      providers in treating disabled people were among the other factors reported by
      PWPDs which influence their decision to seek health care. In order to provide
      inclusive health services, primary health centres need to consider these
      determinants.

PMID- 30186604
TI  - Acute respiratory failure as presentation of late-onset Pompe disease
      complicating the diagnostic process as a labyrinth: a case report.
AB  - Background: Acute respiratory failure can be triggered by several causes, either
      of pulmonary or extra-pulmonary origin. Pompe disease, or type II glycogen
      storage disease, is a serious and often fatal disorder, due to a pathological
      accumulation of glycogen caused by a defective activiy of acid alpha-glucosidase
      (acid maltase), a lysosomal enzyme involved in glycogen degradation. The
      prevalence of the disease is estimated between 1 in 40,000 to 1 in 300,000
      subjects. Case presentation: This case report describes a difficult diagnosis of
      late-onset Pompe disease (LOPD) in a 52 year old Caucasian woman with acute
      respiratory failure requiring orotracheal intubation and subsequent tracheostomy
      for long-term mechanical ventilation 24 h/day. Despite a complex diagnostic
      process including several blood tests, bronchoscopy with BAL, chest CT, brain
      NMR, electromyographies, only a muscle biopsy allowed to reach the correct
      diagnosis. Discussion: The most frequent presentation of myopathies, including
      LOPD, is proximal limb muscle weakness. Respiratory related symptoms (dyspnea on
      effort, reduced physical capacity, recurrent infections, etc.) and respiratory
      failure are often evident in the later stages of the diseases, but they have been
      rarely described as the onset symptoms in LOPD. In our case, a third stage LOPD,
      the cooperation between pulmonologists and neurologists was crucial in reaching a
      correct diagnosis despite a very complex clinical scenario due to different
      confounding co-morbidities as potential causes of respiratory failure and an
      atypical presentation. In this patient, enzyme replacement therapy with infusion
      of alglucosidase alfa was associated with progressive reduction of ventilatory
      support to night hours, and recovery of autonomous walking.

PMID- 30186606
TI  - First reported case of afatinib-associated toxic megacolon.
AB  - We report the first case of toxic megacolon associated with afatinib use, which
      is a potentially fatal complication, with risks of colonic perforation. In this
      case, the condition improved on stopping afatnib. Clinicians need to be alert of
      this rare but fatal adverse effect and to avoid anti-diarrhoeal agents, which can
      worsen toxic megacolon. Anti-diarrhoeal agents are routinely given if diarrhoea
      occurs on afatinib. These should be stopped and avoided if toxic megacolon
      occurs.

PMID- 30186605
TI  - Cognitive behavioural therapy for eating disorders: how do clinician
      characteristics impact on treatment fidelity?
AB  - Background: Clinicians routinely report not practising evidence-based treatments
      with eating disorders. There has been limited research investigating the impact
      of adaptable clinician characteristics such as self-efficacy and therapeutic
      optimism in this area. This study evaluated if there is a relationship between
      clinician therapeutic optimism, self-efficacy and the provision of evidence-based
      practice in the treatment of bulimia nervosa and binge eating disorder. Method: A
      survey developed for this study was administered to 100 psychologists who were
      recruited online via a range of organisations affiliated with psychology and/or
      eating disorders. The survey measured demographic factors, eating disorder
      treatment knowledge, treatment fidelity, the use of individual treatment
      components and a range of clinician characteristics including self-efficacy and
      therapeutic optimism. Results: Results demonstrated that clinician self-efficacy
      was positively associated with and predicted treatment fidelity. Therapeutic
      optimism had significant low correlations with treatment fidelity but did not
      predict treatment fidelity. Conclusion: These findings would suggest that
      strengthening clinician self-efficacy is useful in improving evidence-based
      practice in the treatment of binge eating disorder and bulimia nervosa and may
      also have implications in the training of clinicians. The study also demonstrated
      that the use of a range of knowledge translation strategies are valuable in
      enhancing clinician adherence to evidence-based practice. Further research with
      direct measures of treatment fidelity is needed to clarify these findings.

PMID- 30186607
TI  - Multifocal thymic cysts with cholesterol granuloma.
AB  - A 56-year-old female presented to our department with chest discomfort. Contrast
      enhanced computed tomography (CT) revealed a cyst and nodule in the anterior
      mediastinum; positron emission tomography-CT showed an increased uptake in the
      nodule. Total thymectomy was performed to obtain a definitive diagnosis and
      treatment. A pathological diagnosis of multifocal thymic cysts with cholesterol
      granuloma was made. Microscopic examination revealed different-sized cysts
      scattered in the thymus. These cysts were filled with cholesterol clefts and
      manifested three different phase characters. The nodule comprised granuloma
      containing cholesterol clefts. We report a rare case of a patient whose
      histopathology presented a series of cholesterol granuloma formations.

PMID- 30186608
TI  - Gel electrophoresis of human sperm: a simple method for evaluating sperm protein
      quality.
AB  - Background: The limitations of conventional sperm analyses have highlighted the
      need for additional means of evaluating sperm quality. Methods: In a study of a
      cohort of 245 men with known conventional sperm parameters, one-dimensional PAGE
      was used to monitor protein content and quality in samples from individual
      ejaculates. Results: The sperm protein content varied markedly from sample to
      another, especially in the high-molecular-weight range. The intensity of the 80
      110 kDa bands was correlated with progressive motility (r = 0.15, p = 0.015) and
      was significantly higher (p = 0.0367) in the group of men with conventional
      parameters above the World Health Organization's 2010 reference values than in
      the group with at least one subnormal parameter (i.e. semen volume, sperm
      concentration, sperm count per ejaculate, progressive motility, proportion of
      normal forms or multiple anomaly index below the lower reference value). Using
      mass spectrometry, the 80-110 kDa bands were found to correspond primarily to
      three proteins from the flagellum's fibrous sheath: A-kinase anchor protein 4, A
      kinase anchor protein 3, and spermatogenic cell-specific type 1 hexokinase.
      Conclusion: One-dimensional PAGE constitutes a simple, rapid, reliable,
      inexpensive method for analyzing proteins associated with sperm motility in
      individual human ejaculates.

PMID- 30186609
TI  - A new adult AML case with an extremely complex karyotype, remission and relapse
      combined with high hyperdiploidy of a normal chromosome set in secondary AML.
AB  - Background: Chromosomal abnormalities are diagnostic and prognostic key factors
      in acute myeloid leukemia (AML) patients, as they play a central role for risk
      stratification algorithms. High hyperdiploidy (HH), a rare cytogenetic
      abnormality seen commonly in elder male AML patients, is normally categorized
      under AML with complex karyotype (CK). Accordingly, patients with HH generally
      are associated with low remission rates and a short overall survival. Case
      presentation: Here we report a case of 21-year-old female, diagnosed with a de
      novo AML-M1 according to WHO classification and a CK at diagnosis. Cytogenetic,
      molecular cytogenetic approaches (standard fluorescence in situ hybridization
      (FISH), array-proven multicolor banding (aMCB)) and high resolution array
      comparative genomic hybridization (aCGH) analyses revealed a unique complex but
      still near diploid karyotype involving eleven chromosomes was identified. It
      included pentasomy 4, three yet unreported chromosomal aberrations
      t(1;2)(p35;p22), t(1;3)(p36.2;p26.2), and t(10;12)(p15.2;q24.11), and a
      combination of two cytogenetic events, yet unreported to appear in together, i.e.
      a reciprocal translocation t(1;3)(p36.2;p26.2) leading to EVI1/PRDM16 gene
      fusion, and monoallelic loss of tumor suppressor gene TP53. After successful
      chemotherapeutic treatment the patient experienced a relapse to AML-M1, and she
      developed secondary AML-M6 with tetraploidy and HH. Unfortunately, the young
      woman died 8.5 months after initial diagnosis. Conclusions: To the best of our
      knowledge, a comparable adult AML associated with such a CK, coexistence of 3q
      rearrangements with loss of TP53 at diagnosis, and HH in secondary AML were not
      previously reported. Thus, the combination of the here seen chromosomal
      aberrations in adult primary AML seems to indicate for an adverse prognosis.

PMID- 30186610
TI  - Evaluation and characterization of tumor lysis syndrome before and after
      chemotherapy among pediatric oncology patients in Tikur Anbessa specialized
      hospital, Addis Ababa, Ethiopia.
AB  - Background: Tumor lysis syndrome (TLS) is a life-threatening emergency disorder,
      caused by an abrupt release of intracellular metabolites after tumor cell death.
      It is characterized by a series of metabolic manifestations, especially
      hyperuricemia, hyperkalemia, hyperphosphatemia and hypocalcemia. The aim of this
      study was to evaluate and characterize the incidence of tumor lysis syndrome
      among pediatric oncology patients before and after treatment. Methods: Hospital
      based prospective cohort study was conducted for 6 months on 61 newly diagnosed
      pediatric oncology patients. Socio-demographic data was collected by interview
      administered questionnaire. Patients were followed and the physical diagnosis,
      imaging and laboratory results were interpreted by senior physicians. Data was
      entered to and analyzed by SPSS version 23. Results: Among 61 pediatric oncology
      patients 39(63.9%) were males. The mean (+/-SD) age of the pediatric patients was
      6.39 (+/- 3.67) years ranging from 2 months to 14 years. 29.5% of patients were
      found to have TLS. There were 11.5% and 18.0% of laboratory TLS (LTLS) and
      clinical TLS (CTLS) cases respectively. There were72.2% spontaneous and 27.8%
      treatment induced TLS cases with 23% and 21.3% cases of hyperuricemia and 4.9%
      and 6.6% cases of hyperkalemia incidence before and after treatment respectively.
      Only two patients died, in the study period, due to TLS. Conclusion: There was
      high incidence of TLS irrespective of socio-demographic variation among study
      participants, suggesting that children with cancer are at risk of developing TLS.
      As TLS is a life-threatening complication of malignancies, early identification
      of patients at risk and reducing morbidity and mortality is crucially important.

PMID- 30186611
TI  - An analysis of pharmacy workforce capacity in Nigeria.
AB  - Background: Pharmacists are critical for attaining the goal of universal health
      coverage and equitable access to essential health services, particularly in
      relation to access to medicines and medicines expertise. We describe an analysis
      of the pharmacy workforce in Nigeria from 2011 to 2016 in order to gain insight
      on capacity and to inform pharmacy workforce planning and policy development in
      the country. Method: The study was conducted using census data obtained from the
      Pharmacists Council of Nigeria (PCN) via a validated data collection tool. The
      statistical methods used for analysis were descriptive (frequencies, percentages,
      mean) and linear regression. Secondary data on population distribution per state
      was obtained from the Federal Bureau of Statistics and the National Population
      Commission (NPC) of Nigeria. Result: The data showed 21,892 registered
      pharmacists with only 59% (n = 12,807) in active professional practice. There are
      also more male (62%) compared to female pharmacists while 42% of the licensed
      workforce with known area of practice are in community practice followed by
      hospital pharmacy (11%). A rise in number of pharmacists (0.53-0.66) and new
      pharmacy graduates per year (0.062-0.083) per 10,000 population was observed over
      the five years analysed; however the overall density remains significantly low.
      Pharmacists' density also varied considerably between states (Median = 0.39; Min 
      Max: 0.05-4.3). Regionally, more than a third (~ 40%) of the licensed workforce
      and community pharmacies are situated in the South West region with fewer than
      10% of the total in the North East and North West regions combined. A steady
      decline in number of pharmacists requesting a "letter of good standing" from PCN,
      a proxy measure of intent to migrate was also observed. Conclusion: The data
      indicate ongoing deficits in availability and supply of pharmacists in the
      country with widespread variance in distribution observed across the 36 states
      and the Federal Capital Territory (FCT). The findings suggest that observed
      deficits are not solely related to out-migration and highlights the need for
      policies that will promote increased within-country availability, equitable
      distribution and retention, especially in the underserved regions of North East
      and North West of Nigeria.

PMID- 30186612
TI  - An overview of compensated work-related injuries among Korean firefighters from
      2010 to 2015.
AB  - Background: Although one in two firefighters in South Korea have experienced work
      related injuries, there are few studies which show the overview description on
      work-related injuries and its analysis regarding such causes. Therefore, we aimed
      to show the overview of compensated work-related injuries in order to serve
      fundamental data for establishing prevention policies on work-related injuries
      for Korean firefighters. Methods: We requested the all claimed work-related
      injury data of Korean firefighters from 2010 to 2015 to the Korean National Fire
      Agency (NFA). The data from NFA including 2457 claimed cases was analyzed and we
      confirmed, 2154 approved work-related injuries for the kinds of job activities,
      cause of accident and type of injuries. Among 2154 approved cases, we analyzed
      more variables for the sex, age, and job duration of 1344 compensated cases
      through served text file on summary of accident. Results: The Government
      Employees Pension Service (GEPS) recognized 2154 (87.7%) approved work-related
      injuries among 2457 claimed cases. The incidence of work-related injuries per
      1000 firefighters was 9.8 persons. By region, the incidence of work-related
      injuries per 1000 firefighters ranged from a maximum of 14.5 to a minimum of 4.0.
      The most common job activity caused the accident was fire suppression (18.0%),
      followed by Emergency medical services (EMS) (17.5%) and training (10.7%). The
      most common cause of these accident was movement imbalance (30.3%), followed by
      falls (18.9%) and traffic accident (13.4%). In these work-related injuries,
      sprains and bruises were the most common type of injury (27.2%), and the most
      commonly injured body site was the upper and lower back (25.3%). Data from
      identified 1344 firefighters showed that 1264 (94.0%) were male and 80 (6.0%)
      were female. Age group was the highest in the 40s with 623 cases (46.4%), and job
      duration was the highest with 650 cases in 5-10 years (48.4%). Conclusion: In
      this study, we could obtain the preliminary data necessary to establish
      preventive measures, including the cause of accident and region with high
      accident rates. However, the number of applications for compensated injuries was
      very small compared to the frequency of injuries found in previous studies. The
      lack of appropriate treatment suggested that many firefighter injuries can become
      chronic. In this study, we suggest that it is necessary to introduce an injury
      monitoring system and improve the accessibility of compensated injuries. Trial
      registration: CR318031. Registered 20 June 2018.

PMID- 30186613
TI  - Association of Metabolic Markers with self-reported osteoarthritis among middle
      aged BMI-defined non-obese individuals: a cross-sectional study.
AB  - Background: Osteoarthritis (OA) is a chronic degenerative joint disease. While it
      is well-established that obesity affects OA through increased axial loading on
      the joint cartilage, the indirect effect of obesity through metabolic processes
      among the body mass index (BMI)-defined non-obese population, i.e., BMI < 30
      kg/m2, is less known. Our goal was to evaluate the association of metabolic
      markers including body fat percentage (BF%), waist circumference, maximum weight
      gain during adulthood and serum creatinine with self-reported OA to establish if
      such measures offer additional information over BMI among the non-obese
      population between 40 and 65 years of age. Methods: Cross-sectional data from two
      cycles of the Canadian Health Measures Survey (CHMS) in 2007-2009 and 2009-2011
      were analyzed. Sex-specific logistic regression models were developed to evaluate
      the association of self-reported OA with metabolic markers. Models were
      separately adjusted for age, BMI categories and serum creatinine, and a
      stratified analysis across BM categories was performed. In a secondary analysis,
      we evaluated the association of self-reported OA, cardiovascular diseases and
      hypertension across BF% categories. Results: Of 2462 individuals, 217 (8.8%) self
      reported OA. After adjusting for age and BMI, those within BF%-defined
      overweight/obese category had 2.67 (95% CI: 1.32-3.51) and 2.11(95% CI: 1.38
      3.21) times higher odds of reporting self-reported OA compared to those within
      BF%-defined athletic/acceptable category for females and males, respectively. BF%
      was also significantly associated with self-reported OA after adjusting for age
      and serum creatinine only among females (OR: 1.47, 95%CI: 1.12-1.84).
      Furthermore, among the BMI-defined overweight group, the age-adjusted odds of
      self-reported OA was significantly higher for overweight/obese BF% compared to
      athletic/acceptable BF% in both females and males. In a secondary analysis, we
      showed that the association of self-reported OA and hypertension/cardiovascular
      diseases is significantly higher among BF% overweight/obese (OR: 1.37, 95%CI:
      1.19-3.09) compared to BF% athletic/acceptable (OR: 1.13, 95%CI: 0.87-2.82).
      Conclusion: Our results provide corroborating evidence for a relationship between
      body fat and OA in a population-based study, while no significant independent
      correlates were found between other metabolic markers and OA prevalence. Future
      investigation on the longitudinal relationship between BF and OA among this sub
      population may inform targeted prevention opportunities.

PMID- 30186614
TI  - The Risk of Adverse Events in Patients With Polycystic Kidney Disease With
      Advanced Chronic Kidney Disease.
AB  - Background: Polycystic kidney disease (PKD) leads to progressive chronic kidney
      disease (CKD) with a subsequent risk of adverse events such as cardiac disease,
      infections, end-stage kidney disease (ESKD), and mortality. Objectives: To
      determine the risks of CKD-related adverse outcomes in patients with PKD compared
      with patients without PKD. Setting: Canadian study of prediction of death,
      dialysis and interim cardiovascular events (CanPREDDICT) was a prospective pan
      Canadian cohort study from 2008-2013 involving 28 facilities with adjudicated
      outcomes. Patients: Adult CKD patients (estimated glomerular filtration rate
      [eGFR] = 15-45 mL/min/1.73 m2) under the care of a nephrologist. Measurements:
      Polycystic kidney disease as identified by the treating physician. Methods:
      Patients with PKD (PKD) and non-PKD were propensity score (PS) matched (1:4)
      using demographics, comorbidities, and laboratory values. We used conditional Cox
      proportional hazards models to examine the risk of cardiac disease (defined as
      coronary artery disease or congestive heart failure), infection, ESKD, or all
      cause mortality in patients with PKD compared with no PKD. Results: Among a total
      of 2370 patients, 105 with PKD were matched with 416 without PKD with a baseline
      mean age and eGFR of 62.6 years and 27.8 mL/min, respectively. During 1680 person
      years of follow time (median follow-up: 3.8 years), there were a total of 43
      cardiac, 83 ESKD, 117 infectious, and 39 all-cause mortality events. PKD was
      associated with a higher risk of cardiac events (9.5% vs 7.9%, hazard ratio [HR]
      = 1.46, 95% confidence interval [CI] = 1.04-2.04) and ESKD (25.7% vs 13.5%, HR =
      2.00, 95% CI = 1.33-3.01), and with similar risks for infection (21.9% vs 22.6%,
      HR = 1.16, 95% CI = 0.75-1.82) or all-cause mortality (6.7% vs 7.7%, HR = 0.87,
      95% CI = 0.40-1.91) compared with non-PKD. There were no differences in the types
      of infections (urinary, respiratory, hematologic, or other) between the 2 groups
      (P = .585). Conclusions: Patients with PKD with advanced CKD are at a potentially
      higher risk of ESKD and cardiac events compared with patients without PKD. These
      findings, if confirmed in larger cohorts, suggest that monitoring and treatment
      for adverse outcomes in patients with PKD, especially related to cardiac disease,
      may be beneficial.

PMID- 30186615
TI  - Low concentrations of clarithromycin upregulate cellular antioxidant enzymes and
      phosphorylation of extracellular signal-regulated kinase in human small airway
      epithelial cells.
AB  - Background: It is well known that low-dose, long-term macrolide therapy is
      effective against chronic inflammatory airway diseases. Oxidative stress is
      considered to be a key pathogenesis factor in those diseases. However, the
      mechanism of action of low-dose, long-term macrolide therapy remains unclear. We
      have reported that clarithromycin (CAM), which is a representative macrolide
      antibiotic, could inhibit hydrogen peroxide (H2O2)-induced reduction of the
      glutathione (GSH)/glutathione disulfide (GSSG) ratio in human small airway
      epithelial cells (SAECs), via the maintenance of GSH levels through an effect on
      gamma-glutamylcysteine synthetase (gamma-GCS) expression. In this study, we
      examined the influence of CAM against H2O2-induced activities of cellular
      antioxidant enzymes and phosphorylated extracellular signal regulatory kinase (p
      ERK) using SAECs, the main cells involved in chronic airway inflammatory
      diseases. Methods: SAECs were pretreated with CAM (1, 5, and 10 MUM) for 72 h,
      and subsequently exposed to H2O2 (100 MUM) for 0.5-2 h. Levels of GSH and GSSG,
      and activities of glutathione peroxidase (GPx)-1, glutathione reductase (GR),
      superoxide dismutase (SOD), catalase (CAT), heme oxygenase (HO)-1 and p-ERK were
      assayed. mRNA expressions of GPx-1 and HO-1 were measured using the real-time
      reverse transcription polymerase chain reaction (RT-PCR). Tukey's multiple
      comparison test was used for analysis of statistical significance. Results:
      Pretreatment with low-dose (1 and 5 MUM) CAM for 72 h inhibited H2O2-induced
      reductions of GPx-1, GR, SOD, CAT and HO-1 activities, and mRNA expressions of
      GPx-1 and HO-1, and improved the GSH/GSSG ratio. However, these alterations were
      not observed after pretreatment with high-dose (10 MUM) CAM, which suppressed
      phosphorylation of cell proliferation-associated ERK to cause a significant (p <
      0.01) decrease in cell viability. Conclusions: CAM is efficacious against
      deterioration of cellular antioxidant enzyme activity caused by oxidative stress
      under low-dose, long-term treatment conditions. On the other hand, pretreatment
      with high-dose CAM suppressed phosphorylation of cell proliferation-associated
      ERK and decreased cell viability. The present study may provide additional
      evidence as to why low-dose, long-term administration of macrolides is effective
      for treating chronic inflammatory airway diseases.

PMID- 30186616
TI  - First report of nodular skin lesions caused by Mycobacterium nebraskense in a 9
      year-old cat.
AB  - Case summary: A 9-year-old cat was referred with multiple, raised, ulcerative
      skin nodules in the region of the neck and dorsal head. Histopathological
      findings of a biopsied nodule were granulomatous dermatitis and panniculitis
      without multinucleated giant cells or caseous necrosis. In addition, by Ziehl
      Neelsen staining numerous acid-fast intracellular bacilli were observed within
      the lesions. Mycobacterial culture showed growth of rough scotochromogenic
      colonies after 3 weeks of incubation. Molecular characterisation of the isolate
      identified Mycobacterium nebraskense as the cause of the infection. No phenotypic
      resistance was detected for the antimycobacterial agents tested. The cat was
      successfully treated with a combination of surgical excision and a 12 week course
      of antimicrobial therapy, including rifampicin combined with clarithromycin.
      Relevance and novel information: To our knowledge, this is the first documented
      case of mycobacterial granulomatous dermatitis and panniculitis due to M
      nebraskense infection in a cat. The successful surgical and antimycobacterial
      treatment regimen is described.

PMID- 30186617
TI  - Recanalisation of a congenital extrahepatic portosystemic shunt previously
      attenuated with cellophane banding in a cat.
AB  - Case summary: A congenital extrahepatic portosystemic shunt was attenuated with
      commercial roll cellophane banding in a cat and postoperative liver changes were
      monitored using CT angiography (CTA). The patient clinically improved after
      cellophane banding, characterised by resolution of hepatic encephalopathy, weight
      gain, reference interval (RI) bile acid stimulation tests, as well as CTA
      documented increased liver size, increased hepatic vasculature and shunt
      attenuation. Six months later the cat re-presented with recurrence of clinical
      signs and increased bile acids. CTA confirmed recanalisation of the shunt. Shunt
      attenuation was repeated using pure cellophane banding and nearly complete
      closure of the shunt was later documented by CTA. Seven months later,
      recanalisation was again documented via CTA and associated with clinical signs
      and increased bile acids. Complete ligation of the shunt was achieved using a
      polypropylene ligature and a titanium ligating clip. At long-term follow-up, the
      cat was clinically well, and bile acids and biochemistry were within the RIs.
      Relevance and novel information: This is the first report of CTA-documented
      recanalisation of an extrahepatic portosystemic shunt previously attenuated with
      cellophane banding. Recanalisation should be considered as a differential for
      recurrence of hepatic encephalopathy following cellophane banding.

PMID- 30186618
TI  - Paging the eCardiologist: insights into referral behaviour of primary care
      physicians from qualitative analysis of a cardiology eConsult service.
AB  - Objective: The purpose of this study is to investigate determinants of primary
      care physician cardiology referrals by performing qualitative analysis of
      questions asked by primary care physicians in cardiology electronic consultation
      services (eConsults). Setting: A health region in eastern Ontario, Canada, where
      primary care providers have had access to an eConsult service since 2010.
      Participants: We included all consecutive cardiology eConsults initiated by
      registered primary care provider users of our eConsult service and who initiated
      one or more eConsult between July 2014 and January 2015. We excluded eConsults in
      which the primary care provider attached a document without asking a question. A
      convenience sample of 100 consecutive eConsults initiated by 61 primary care
      providers was analysed after excluding 14 eConsults.Primary and secondary outcome
      measures: Primary care provider eConsult questions are categorised into thematic
      categories based on the constant comparison method of qualitative analysis with
      external validation by content experts. Secondary outcomes include sample primary
      care provider eConsult questions to illustrate each theme and any emergent
      subthemes. Results: Thematic saturation occurred after analysis of 30 eConsults.
      An additional 70 eConsults were coded with no new emergent themes. Themes include
      exceptions to clinical guidelines (n=13), non-cardiac treatment in a cardiac
      patient (n=13), specific investigation/management (n=18), interpretation of
      diagnostic testing (n=46), clinical concerns despite normal testing (n=4) and
      screening for positive family history (n=6). Subthemes include multiple
      comorbidities and mild abnormalities on cardiac tests. Conclusions: We report
      categories of clinical questions that drive primary care provider cardiology
      eConsults. Multimorbidity leads to cardiology eConsults as primary care providers
      try to apply treatment guidelines in medically complex patients. Mild test
      abnormalities unrelated to clinical problems commonly lead to cardiology eConsult
      requests. Further research is needed to determine how guidelines can better
      account for multimorbidity, and how cardiologists can better communicate with
      primary care providers to put cardiac test results in clinical context.

PMID- 30186619
TI  - Older adults using a patient portal: registration and experiences, one year after
      implementation.
AB  - Background and objectives: The interest of older adults in using patient portals
      is rising, yet subject to functional and usability barriers. This study aims to
      gain insight into registration rates and experiences of older adult patients
      using a patient portal, one year after implementation in an academic hospital.
      Methods: Registration rates for one year were collected via automated data
      extraction. Older adult patients' experiences were collected through a survey,
      available via the portal in the last three months of the year. Results: Older
      adults were a large user group of the patient portal and appreciated its
      functionalities. In one year, 10,679 older adult patients (aged 56+) registered,
      which constituted 47% of total portal registrations. The 131 older adult survey
      respondents had a mean age of 64.5 years and 40% indicated that they liked to
      review their medical information and appointments via the portal. Yet, older
      adults experienced user interaction issues and had higher expectations of content
      within the portal and patient/provider communication through the portal. Of the
      survey respondents, 22% experienced usability issues at login and in viewing test
      results, 15% commented on late or no responses by providers on patients' sent
      messages and 24% expected the portal to provide medical history
      information.Implications: Patient portal designs should be optimized to usability
      needs of older adults. Portals preferably include medical history information,
      physicians' notes and require prompt responses of providers.

PMID- 30186620
TI  - Pain in AQP4-IgG-positive and MOG-IgG-positive neuromyelitis optica spectrum
      disorders.
AB  - Background: Pain is a frequent symptom in aquaporin-4-immunoglobulin-G-positive
      neuromyelitis optica spectrum disorders (AQP4-IgG-pos. NMOSD). Data on pain in
      myelin-oligodendrocyte-glycoprotein-immunoglobulin-G autoimmunity with a clinical
      NMOSD phenotype (MOG-IgG-pos. NMOSD) are scarce. Objective: The objective of this
      paper is to investigate pain in MOG-IgG-pos. NMOSD, AQP4-IgG-pos. NMOSD and NMOSD
      without AQP4/MOG-IgG detection (AQP4/MOG-IgG-neg. NMOSD). Methods: Forty-nine MOG
      IgG-pos. (n = 14), AQP4-IgG-pos. (n = 29) and AQP4/MOG-IgG-neg. (n = 6) NMOSD
      patients were included in this cross-sectional baseline analysis from an ongoing
      observational study. We identified spinal cord lesions on magnetic resonance
      imaging, assessed pain by the painDETECT and McGill Pain questionnaires, quality
      of life by Short Form Health Survey, and depression by Beck Depression Inventory.
      Results: Twelve MOG-IgG-pos. NMOSD patients (86%), 24 AQP4-IgG-pos. NMOSD
      patients (83%), and all AQP4/MOG-IgG-neg. NMOSD patients (100%) suffered from
      pain. MOG-IgG-pos. NMOSD patients had mostly neuropathic pain and headache; AQP4
      IgG-pos. and AQP4/MOG-IgG-neg. NMOSD patients had mostly neuropathic pain. A
      history of myelitis was less frequent in MOG-IgG-pos. NMOSD than in AQP4-IgG-pos.
      NMOSD patients. Pain influenced quality of life in all patients. Thirty-six
      percent of patients with pain received pain medication; none of them were free of
      pain. Conclusions: Pain is a frequent symptom of patients with MOG-IgG-pos. NMOSD
      and is as important as in AQP4-IgG-pos. and AQP4/MOG-IgG-neg. NMOSD. Despite its
      impact on quality of life, pain is insufficiently alleviated by medication.

PMID- 30186621
TI  - Diarrhoea in neonatal piglets: a case control study on microbiological findings.
AB  - Background: Many factors can influence the occurrence of neonatal diarrhoea in
      piglets. Currently, well-known pathogens such as enterotoxigenic Escherichia coli
      and Clostridium perfringens type C appear to play a minor role in development of
      disease. Other infectious pathogens may be involved. In this study, we aimed to
      investigate the presence of selected infectious pathogens in neonatal piglets
      with clinical and pathological signs of enteric disease. The association between
      rotavirus A, Enterococcus hirae, Clostridium difficile and Clostridium
      perfringens type A/C and diarrhoea was investigated in a case control study on
      piglet level. The possible role of E. coli virulence factors was investigated in
      a multistep-procedure using herd-pools of E.coli isolates to screen for their
      presence. Results: Rotavirus A was detected more often in cases (25%) than in
      controls (6%) (P < 0.001). The detection rate of Enterococcus hirae, Clostridium
      difficile and C. perfringens type A positive for beta2 genes was the same in the
      two groups of piglets. C. perfringens type C was not detected in the study.
      Investigations on E. coli virulence factors showed a high prevalence of EAST1
      toxin genes (55% of tested case piglets were positive) and AIDA-1 adhesin genes
      (63% of toxin positive case piglets were positive) in case piglets. Conclusions:
      Detection of rotavirus A was statistically significantly associated with neonatal
      piglet diarrhoea.An aetiologic role of E. coli carrying virulence factors EAST1
      and AIDA-1 needs further investigation as the study points out these two factors
      as possible causative factors in neonatal diarrhoea.Detection of E.hirae,
      C.difficile and C. perfringens type A carrying beta 2 genes was not associated
      with neonatal piglet diarrhoea. However, the study suggested that massive
      overgrowth by E. hirae could be part of the pathogenesis in some cases of
      neonatal diarrhoea.

PMID- 30186622
TI  - Correction to: A comprehensive comparison of sex-inducing activity in asexual
      worms of the planarian Dugesia ryukyuensis: the crucial sex-inducing substance
      appears to be present in yolk glands in Tricladida.
AB  - [This corrects the article DOI: 10.1186/s40851-018-0096-9.].

PMID- 30186623
TI  - Clinical characteristics and satisfaction with the fimasartan in Korean
      hypertensive patients: a prospective, cross-sectional and open-label, 8-week
      switching study (Kanarb-hypertension epidemiology medication satisfaction study;
      K-HEMS study).
AB  - Background: Fimasartan (Kanarb; Boryung Pharmaceutical Co., Ltd., Seoul, Republic
      of Korea) is a non-protein angiotensin II receptor blocker that selectively
      blocks the AT1 receptor. No prior large-scale study has investigated the impact
      of demographics, disease, treatment, and clinical characteristics on medication
      satisfaction and quality of life in Korean hypertensive patients. Additionally,
      it is unclear whether increased medication compliance affects the achievement of
      hypertension treatment objectives. Methods: This was a multicenter, non
      interventional, open-label and 8-week switching study. This study was divided
      into 2 steps. STEP I was a cross-sectional study composed entirely of
      hypertensive patients undergoing treatment and STEP II was a prospective
      observational study of hypertensive patients switching to fimasartan. A total of
      12,244 and 2023 patients were analyzed in the STEP I and STEP II groups,
      respectively. In STEP I, we investigated demographics, clinical, disease, and
      treatment characteristics at the registration point and then analyzed medication
      satisfaction, patient compliance, and quality of life. In STEP II, the patients
      who switched to fimasartan were followed up for 8 weeks, and the data analyzed
      included changes in medication effects, satisfaction, compliance, and adverse
      events. Results: Some baseline characteristics, such as sex, body mass index,
      region of residence, educational level, and income level, affected the quality of
      life and medication duration in hypertensive patients. At 4 and 8 weeks, 62.5 and
      69.9% of patients, respectively, reached their target blood pressure. The
      medication satisfaction scores were increased 4.0 +/- 1.2, 5.1 +/- 1.1, and 5.4
      +/- 1.0 at baseline, 4 weeks, and 8 weeks, respectively, and the difference was
      statistically significant (p < 0.0001). Most patients (76.4%) who changed from
      prior antihypertensive drug to fimasartan were not satisfied with conventional
      antihypertensive drugs (e.g., lack of efficacy). Among 2183 patients, 234 adverse
      events occurred in 151 (6.9%) and 50 adverse drug reactions occurred in 39
      (1.8%). Conclusion: The demographic, clinical, disease, and treatment
      characteristics of hypertensive patients were investigated in this study. After
      switching to fimasartan, blood pressure was significantly decreased and patient
      satisfaction was improved. Fimasartan treatment was well tolerated and safe in
      hypertensive patients in Korea.Trial registration. Trial registration:
      ClinicalTrials.gov Identifier: (NCT02394392).

PMID- 30186624
TI  - Development of a standard form for assessing research grant applications from the
      perspective of patients.
AB  - Background: Health-research funding organizations are increasingly involving
      patient representatives in the assessment of grant applications. However, there
      is no consensus on an appropriate scope or definition of the patient perspective
      and the eligibility of potential patient reviewers to take on this role. The aim
      of our study is to develop a consensus-based template for patient reviewers to
      assess research grant applications from the patients' perspective. We also
      defined a glossary of terms and definitions to help the patient reviewers in
      their assessment role. Methods: Together with members of the Dutch Association of
      Health Care Funds (SGF) we developed an assessment form for patient reviewers
      following constant comparative analysis of existing review forms, a survey among
      all stakeholders, testing in three pilot training sessions, and a structured
      consensus process. Results: A small SGF working group collected and analysed 20
      patient assessment forms, used by 12 health foundations and one patient
      organization. One systematic literature review was included. By comparing and
      discussing items and assessment categories in subsequent workshops, a first
      template form was developed. This version was electronically distributed among
      the members of 10 patient panels of whom 67 patient reviewers filled in the
      survey. A second version was then presented at a final working group meeting
      where consensus was reached about a template with 12 categories covering 41 items
      important for patients. A brochure for patient reviewers, a guide for panel
      coordinators and a glossary were developed to accompany future implementation of
      the template. Conclusions: A template for patient reviewers to assess research
      grant applications is now available, based on the consensus of 21 Dutch health
      foundations.

PMID- 30186625
TI  - Characterizing the multiplicity of HIV founder variants during sexual
      transmission among MSM.
AB  - Transmission of multiple founder variants has been associated with faster HIV
      disease progression. Many studies have attempted to determine the number of
      founder variants, mainly by analysis of sequence diversity and/or tree topology
      from acutely HIV-infected individuals. We hypothesized that adding sequence data
      collected from source partners might improve resolution and characterization of
      transmission events. Blood plasma samples were collected from both the source and
      recipient in thirty epidemiologically- and phylogenetically linked transmission
      pairs. All were men who have sex with men, sampled on average 70 days (range 11
      170) after the recipient's estimated date of infection. Next generation
      sequencing (454 FLX, Roche) of HIV-1 env (C2-V3) was performed for all samples.
      Inspection of sequence alignments, highlighter plots, phylogenetic tree
      topologies and sequence diversity were used to determine the multiplicity of
      founder viruses with and without the inclusion of source data. Using only
      recipient sequence data, we were able to resolve multiplicity in twenty-six of
      the thirty transmission pairs (87 percent). Among them, five presented with a
      high viral diversity at baseline (>0.10 subst/site), consistent with multiple
      founders. By incorporating sequence data collected from the source partner, we
      were able to characterize all thirty transmission pairs. Overall, sixteen
      transmission events (53.3 percent) involved multiple founders. Results obtained
      by combining sequence data from recipient and source were congruent for nineteen
      of the twenty-six (73 percent) cases where conclusions were made using only
      recipient sequence data. The multiplicity of founders was associated with
      significantly higher HIV RNA levels (P = 0.04). To further evaluate the
      transmission bottleneck, we focused on single founder transmissions (fourteen of
      the thirty), and identified four recipients (28.6 percent) that had founder
      variants that were inferred to arise from minority viral populations in the
      source. These source clades ranged from 1.0 to 5.4 percent of the sampled
      population. Incorporating sequence data from the source increased of the ability
      to determine the multiplicity of founder variants, reduced misclassification, and
      allowed us to infer the transmission of minority variants.

PMID- 30186626
TI  - Bone density measurements adjacent to acetabular cups in total hip arthroplasty
      using dual-energy CT: an in vivo reliability and agreement study.
AB  - Background: Measuring bone mineral density (BMD) around acetabular prosthetic
      components with computed tomography (CT) is challenged by the complex anatomy and
      metal artifacts. Three-dimensional (3D) segmentation is required for the
      analysis, but it is usually not practically applicable on current CT
      workstations. Purpose: To test the between-scan agreement and reliability of
      custom segmentation software for BMD measurements adjacent to cemented and
      uncemented acetabular cups in dual-energy CT (DECT). Material and Methods: Twenty
      four male patients with total hip arthroplasty were scanned and rescanned using
      130-keV virtual monochromatic DECT images. Hemispherical regions of interest were
      defined slice-by-slice and BMD was calculated around the acetabular cup using
      custom segmentation software. Results: In the uncemented cup, the mean BMD was
      153 mg/cm3 with a between-scan difference of 10 mg/cm3 (P < 0.0001). In the
      cemented cup, the mean BMD was 186 mg/cm3 with a between-scan difference of 6
      mg/cm3 (P = 0.15). In both uncemented and cemented cups the intraclass
      correlation coefficient between repeated measurements was >0.95 and narrow Bland
      Altman Limits of Agreement. Conclusion: BMD can be measured with high absolute
      between-scan agreement and good reliability adjacent to acetabular cemented and
      uncemented cups using DECT and segmentation software.

PMID- 30186627
TI  - Fluorescein Leakage within Recent Subretinal Hemorrhage in Pathologic Myopia:
      Suggestive of CNV?
AB  - Purpose: To determine whether fluorescein leakage within subretinal hemorrhage is
      definitely suggestive of choroidal neovascularization (CNV) by multimodal imaging
      including optical coherence tomography angiography (OCTA). Methods: Twenty-five
      consecutive highly myopic patients (25 eyes) with fluorescein leakage within
      subretinal hemorrhage detected within 1 month were prospectively included. All
      patients underwent OCTA and spectral-domain optical coherence tomography (SD
      OCT). The OCTA and SD-OCT findings at the site of fluorescein leakage were
      analyzed. In cases of a doubtful diagnosis, indocyanine green angiography (ICGA)
      was also performed to differentiate myopic CNV from lacquer crack if necessary;
      all patients were followed up by SD-OCT and/or OCTA for at least 2 weeks.
      Results: In terms of the site of fluorescein leakage, OCTA revealed an abnormal
      vascular network in the outer retina and a choriocapillaris slab in 22 out of 25
      eyes (88%), which were confirmed to be CNV. However, no high-flow signal was
      observed in 3 of 25 eyes (12%). In these 3 cases, SD-OCT showed a focal rupture
      of the retinal pigment epithelium-Bruch's membrane-choriocapillaris (RPE-BM-CC)
      complex and a columnar hyperreflective signal of blood originating from defects
      with a volcanic geyser-like appearance, and no exudative signs were detected.
      Notably, all ruptures of the RPE-BM-CC complex were located exactly at lacquer
      crack sites. Moreover, with the absorption of subretinal hemorrhage, ruptures of
      the RPE-BM-CC complex spontaneously resolved without any intervention.
      Considering the multimodal imaging appearance and follow-up outcomes, these 3
      eyes were eventually diagnosed as simple bleeding associated with lacquer cracks.
      Conclusions: Dye leakage within recent subretinal hemorrhage on FA could be
      caused by new-onset lacquer cracks in pathologic myopia. Multimodal imaging
      including OCTA is helpful to differentiate lacquer cracks from myopic CNV.

PMID- 30186628
TI  - Graft Survival after Penetrating Keratoplasty in Cases of Trabeculectomy versus
      Ahmed Valve Implant.
AB  - Purpose: To compare the corneal graft survival rates after penetrating
      keratoplasty (PKP) in cases of post-PKP glaucoma managed by either trabeculectomy
      with mitomycin C or Ahmed glaucoma valve (AGV). Methods: This study was a
      retrospective interventional comparative study that included 40 eyes of 40
      patients. The included patients had undergone previous PKP for anterior segment
      reconstruction after microbial or fungal keratitis, chemical burns, trauma, or
      perforated corneal ulcer. Post-PKP glaucoma was managed surgically by either
      trabeculectomy with mitomycin C (group 1) or Ahmed glaucoma valve (group 2).
      Results: The first group (n=20) had undergone trabeculectomy with MMC, and the
      second group (n=20) had undergone AGV implantation. Regarding BCVA, there was no
      statistically significant difference between the 2 groups. Mean IOP was
      significantly lower in the AGV group at 6 months, 12 months, and 24 months
      (p=0.001). Mean IOP at 24 months dropped significantly from preglaucoma surgery
      levels in both groups (p=0.001). Rejection episodes occurred in 2 eyes (10%) of
      the trabeculectomy group versus 8 eyes (40%) in the AGV group (p=0.028). In the
      trabeculectomy group, corneal graft failure occurred in 1 (5%), 3 (15%), and 6
      (30%) eyes at 6 months, 12 months, and 24 months, respectively. In the AGV group,
      corneal graft failure occurred in 2 (10%), 5 (25%), and 10 (50%) eyes at 6
      months, 12 months, and 24 months, respectively. The mean time to failure in the
      trabeculectomy group was 12.33 +/- 5.60 months versus 11.90 +/- 5.70 months in
      the AGV group (p=0.027). Conclusion: Managing postpenetrating keratoplasty
      glaucoma could be bothersome especially in complex cases. Ahmed glaucoma valve
      implant controls the intraocular pressure more effectively than trabeculectomy
      with mitomycin C. However, Ahmed glaucoma valve can result in higher rates of
      corneal graft failure in a shorter duration of time. This trial is registered
      with PACTR201712002861391 on 21 Dec 2017.

PMID- 30186629
TI  - Prevalence, Treatment, and Associated Factors of Hypertension in Spain: A
      Comparative Study between Populations.
AB  - The prevalence and related factors of hypertensive subjects according to the
      resident area (rural versus urban) were investigated in two population-based
      studies from Spain. Medical questionnaires were administered and anthropometrics
      were measured, using standardized protocols. Hypertension was diagnosed in
      pharmacology treated subjects or those with blood pressure (BP) >=140/90 mm Hg.
      Regarding BP control, it was defined as under control if BP was <140/90 or
      <140/85 mm Hg in type 2 diabetic subjects. Information on educational status,
      social class, smoking habit, and alcohol intake was obtained. 3,816 subjects
      (54.38 % women) were included. Prevalence of diagnosed hypertension was higher in
      women and showed no differences according to the living area (men: urban 21.88
      versus rural 21.92 %, p = 0.986; women: urban 28.73 versus rural 30.01 %, p =
      0.540). Women living in rural areas and men with secondary or tertiary education
      levels had a lower probability of being BP uncontrolled (OR (95 % CI): 0.501
      (0.258-0.970)/p=0.040, 0.245 (0.092-0.654)/p=0.005, and 0.156 (0.044
      0.549)/p=0.004, respectively). Urban young men (31-45 years) and medium aged
      women (46-60 years) were less BP controlled than their rural counterparts (41.30
      versus 65.79 %/p=0.025 and 35.24 versus 53.27 %/p=0.002, respectively).

PMID- 30186630
TI  - The Hepatoprotective Effect of Jaboticaba Peel Powder in a Rat Model of Type 2
      Diabetes Mellitus Involves the Modulation of Thiol/Disulfide Redox State through
      the Upregulation of Glutathione Synthesis.
AB  - Jaboticaba peel powder (JPP) is rich in bioactive compounds, mainly soluble and
      insoluble polyphenols with great antioxidant properties. The aim of this study is
      to evaluate the effects of JPP supplementation on the oxidative stress and
      hepatic damage in a rat model of type 2 diabetes mellitus (T2DM). Diabetic rats
      received vehicle or JPP at 2.7 (JPP-I), 5.4 (JPP-II), or 10.8 (JPP-III) g/L in
      drinking water during 8 weeks. JPP-III attenuated hyperglycaemia and dyslipidemia
      increased by 86% the liver content of nonprotein thiol groups and by 90% the
      GSH/GSSG ratio by activating glutathione synthesis. Accordingly, JPP
      supplementation prevented the loss of activity of the sulfhydryl-dependent enzyme
      delta-aminolaevulinic acid dehydratase and attenuated hepatic injury assessed by
      the reduction of serum aspartate aminotransferase activity and liver hypertrophy.
      Our results support that JPP supplementation to T2DM rats decreases hepatic
      damage most likely by increasing glutathione synthesis and modulating the
      thiol/disulfide redox balance.

PMID- 30186631
TI  - Mortality and Recovery of Renal Function in Acute Kidney Injury Patients Treated
      with Prolonged Intermittent Hemodialysis Sessions Lasting 10 versus 6 Hours:
      Results of a Randomized Clinical Trial.
AB  - Purpose: This trial aimed to compare mortality and recovery of renal function in
      acute kidney injury (AKI) patients treated with different durations of prolonged
      hemodialysis (PHD) sessions (6 h versus 10 h). Methodology: We included patients
      with sepsis-associated AKI, >18 years, who are in use of a norepinephrine (lower
      than 0.7 ucg/kg/min). Results: One hundred and ninety-four patients were treated
      with 531 sessions of PHD (G1=104 and G2=90 patients). The two groups were similar
      in age and SOFA. There was no significant difference in hypotension, hypokalemia,
      and anticoagulation during PHD sessions. The two groups showed differences in
      filter clotting, hypophosphatemia, and treatment discontinuation (12.3 versus
      23.1%, p=0.002; 15.5 versus 25.8%, p=0.005; and 7.9 versus 15.6%, p=0.008,
      respectively). There was no difference in fluid balance (FB) before and after PHD
      sessions. Death and complete recovery of renal function were similar (81.3 versus
      82.2%, p=0.87 and 21 versus 31.2%, p=0.7, respectively). At logistic regression,
      the positive FB before and after dialysis was identified as risk factor for
      death, while volume overload after three PHD sessions and predialysis creatinine
      were negatively associated with recovery of renal function in 28 days.
      Conclusion: There was no difference in the mortality and recovery of renal
      function of AKI patients submitted to different durations of PHD and sessions
      lasting 10 h presented higher filter clotting, hypophosphatemia, and treatment
      discontinuation. ISRCTN Registry number is ISRCTN33774458.

PMID- 30186632
TI  - Vascular Calcification in Chronic Kidney Disease: The Role of Inflammation.
AB  - Cardiovascular complications are extremely frequent in patients with chronic
      kidney disease (CKD) and death from cardiac causes is the most common cause of
      death in this particular population. Cardiovascular disease is approximately 3
      times more frequent in patients with CKD than in other known cardiovascular risk
      groups and cardiovascular mortality is approximately 10-fold more frequent in
      patients on dialysis compared to the age- and sex-matched segments of the
      nonrenal population. Among other structural and functional factors advanced
      calcification of atherosclerotic plaques as well as of the arterial and venous
      media has been described as potentially relevant for this high cardiovascular
      morbidity and mortality. One potential explanation for this exceedingly high
      vascular calcification in animal models as well as in patients with CKD increased
      systemic and most importantly local (micro)inflammation that has been shown to
      favor the development of calcifying particles by multiple ways. Of note, local
      vascular upregulation of proinflammatory and proosteogenic molecules is already
      present at early stages of CKD and may thus be operative for vascular
      calcification. In addition, increased expression of costimulatory molecules and
      mast cells has also been documented in patients with CKD pointing to a more
      inflammatory and potentially less stable phenotype of coronary atherosclerotic
      plaques in CKD.

PMID- 30186633
TI  - Prevalence and Determinants of Complete Postnatal Care Service Utilization in
      Northern Shoa, Ethiopia.
AB  - Background: Postnatal period presents the highest risk of death for mothers and
      newborns. Although progress has been made in expanding the coverage for most of
      maternal health services, national prevalence of postnatal care service
      utilization in Ethiopia is still extremely limited. Hence, this study aims to
      determine the prevalence and factors associated with complete postnatal care
      service utilization in Northern Shoa, Ethiopia. Methods: Community based cross
      sectional survey was conducted between November 2016 and February 2017. A total
      of 510 mothers were included in the study using multistage sampling technique.
      The data were collected through face-to-face interview. Bivariate and
      multivariate logistic regression models were fitted to identify factors
      associated with complete postnatal care utilization at p value of < 0.05. SPSS
      version 20 was used to analyze the data. Results: The prevalence of complete
      postnatal care utilization was found to be 28.4% in the study area. Mode of
      delivery (AOR=5.7, 95% CI = 3.9, 19), number of children (AOR= 2.5 95% CI, 1.4,
      14.2), and level of education (AOR=3.2 95% CI, 1.1, 9.2) were the factors
      statistically associated with complete postnatal service uptake. Being healthy
      was the major (48.8%) reason mentioned for not complying with the recommended
      three postnatal visits. Conclusion: The prevalence of complete postnatal care
      service in the study area was found to be low, and it is far less than the
      targeted zonal and regional plan. Reinforcing the existing policies and
      strategies to increase women level of awareness about postnatal care and
      intensive counseling during antenatal care and delivery are the recommendations
      based upon the current finding.

PMID- 30186634
TI  - Risk and Outcome after Simultaneous Carotid Surgery and Cardiac Surgery: Single
      Centre Experience.
AB  - Objective: Carotid artery stenosis in patients undergoing open-heart surgery may
      increase risk and deteriorate outcome. The aim of the study was the analysis of
      risks and outcome after simultaneous carotid and cardiac surgery. Methods: We
      retrospectively reviewed the medical records of 100 consecutive patients who
      underwent simultaneous carotid surgery and open-heart surgery during a 5-year
      period (from 2006 to 2010). Seventy patients were male and 30 female; the mean
      age was 70.9+/-7.9 years (median: 71.8 years). Seventy-three patients underwent
      coronary bypass grafting (CABG), 18 patients combined CABG and valve procedures,
      7 patients CABG combined with other procedures, and 3 patients isolated valve
      surgery. More than half of patients had had bilateral carotid artery pathology
      (n=51) including contralateral carotid artery occlusion in 12 cases. Results:
      Carotid artery patch plasty was performed in 71 patients and eversion technique
      in 29. In 75 cases an intraluminal shunt was used. Thirty-day mortality rate was
      7% due to cardiac complications (n=5), metabolic disturbance (n=1), and diffuse
      cerebral embolism (n=1). There were no carotid surgery-related deaths.
      Postoperatively, transient cerebral ischemia occurred in one patient and stroke
      with mild permanent neurological deficit (Rankin level 2) in another patient.
      Conclusion: Simultaneous carotid artery surgery and open-heart surgery have low
      risk. The underlying cardiac disease influences outcome.

PMID- 30186635
TI  - Free Radical Scavenging Capacity, Carotenoid Content, and NMR Characterization of
      Blighia sapida Aril Oil.
AB  - Blighia sapida aril oil is rich in monounsaturated fatty acids but is however
      currently not utilized industrially. The oil was characterized utilizing nuclear
      magnetic resonance (NMR) and Fourier Transform Infrared Spectroscopy (FTIR). A
      spectrophotometric assay was conducted to determine the free radical scavenging
      properties and carotenoid content of the oil. Chemical shifts resonating between
      delta 5.30 and 5.32 in the 1H NMR are indicative of olefinic protons present in
      ackee aril oil which are due to the presence of oleic acid. A peak at 3006 cm-1
      in the FTIR spectra confirms the high levels of monounsaturation. The oil has a
      free radical scavenging activity of 48%  +/- 2.8% and carotenoid content of 21 +/
      0.2 ppm.

PMID- 30186636
TI  - Case Report of a Massive Thigh Hematoma after Adductor Canal Block in a Morbidly
      Obese Woman Anticoagulated with Apixaban.
AB  - Hematoma formation after peripheral nerve block placement is a rare event. We
      report a case of a morbidly obese patient who was anticoagulated with apixaban
      and developed a massive thigh hematoma after an ultrasound-guided adductor canal
      block. Despite continuous visualization of the block needle, an unrecognized
      vascular injury occurred leading to a 14-cm hematoma in the anterolateral thigh.
      Morbid obesity warrants additional risk consideration when placing nerve blocks
      in an anticoagulated patient. In addition, early recognition and expert
      consultation are both important in the management of block-related hematomas.

PMID- 30186637
TI  - Streptococcus pyogenes Pericarditis with Resultant Pulmonary Trunk Compression
      Secondary to Mycotic Pseudoaneurysm.
AB  - Purulent pericarditis is a rare disease in the era of antibiotics, with
      Streptococcus pyogenes being a possible, though uncommon etiology. Even more
      uncommon are mycotic aneurysms secondary to group A strep purulent pericarditis
      and bacteremia. We report a case of an 18-year-old female with a history of strep
      pharyngitis develop Streptococcus pyogenes purulent pericarditis with subsequent
      ventricular fibrillation (VF). Following initial stabilization, she ultimately
      developed a 4.8 cm mycotic aneurysm of the ascending aorta, with resultant
      compression of the pulmonary trunk and right pulmonary arteries.

PMID- 30186638
TI  - An Adult with a Remnant Urachus Anomaly Diagnosed in the Emergency Department.
AB  - The urachus is a midline tubular structure that stretches from the apex of the
      bladder and connects to the umbilicus. Urachal remnants result from incomplete
      regression of the fetal urachus in infancy. We report the case of a 21-year-old
      male who presented to the emergency department with purulent drainage from his
      umbilicus in association with a chronic intermittent "pulling sensation" in the
      umbilicus and suprapubic areas. An infected urachal remnant was diagnosed and was
      treated with an oral antibiotic and ultimately with outpatient excision of the
      remnant. Such cases are rare but have the potential to progress to sepsis. In
      addition, chronic inflammation can lead to neoplastic transformation
      (adenocarcinoma). Urachal remnant infections can be considered in adults with
      umbilical purulent drainage. We propose that the "pulling sensation" described
      may be a clue to the diagnosis in some patients in which the urachal remnant is
      attached to the bladder and that the sensation was due to the mechanical
      connection between the bladder and the umbilicus. The sensation resolved
      postremoval status of the remnant. This does not appear to have been previously
      proposed in the literature.

PMID- 30186639
TI  - Traumatic Retropharyngeal Hematoma in a Patient Taking Clopidogrel.
AB  - The development of a retropharyngeal hematoma may lead to acute airway compromise
      requiring emergent airway stabilization. We describe the development of a
      retropharyngeal hematoma in an elderly woman who sustained a fall from standing
      approximately 10 hours prior to symptom onset who was taking the antiplatelet
      agents clopidogrel and aspirin. This delayed onset of rapid airway compromise
      secondary to a retropharyngeal hematoma following a fall in a patient taking
      clopidogrel is an unusual and potentially life threatening event.

PMID- 30186640
TI  - Giant Prolactinoma of Young Onset: A Clue to Diagnosis of MEN-1 Syndrome.
AB  - Multiple endocrine neoplasia (MEN) type 1 syndrome is an autosomal dominant
      disorder caused by germline mutations in MEN1 gene, characterized by tumours in
      endocrine and nonendocrine organs. Giant prolactinoma is defined as tumours
      larger than 40mm with very high prolactin secretion. We report two unrelated Sri
      Lankan patients (8-year-old boy and a 20-year-old female) who presented with
      giant prolactinomas with mass effects of the tumours. The female patient showed
      complete response to medical therapy, while the boy developed recurrent resistant
      prolactinoma needing surgery and radiotherapy. During follow-up, both developed
      pancreatic neuroendocrine tumours. Genetic analysis revealed that one was
      heterozygous for a nonsense mutation and other for missense mutation in MEN1
      gene. Screening confirmed familial MEN-1 syndrome in their families. High
      clinical suspicion upon unusual clinical presentation prompted genetic evaluation
      in these patients and detection of MEN1 gene mutation. Pituitary adenomas in
      children with MEN-1 syndrome are larger tumours with higher rates of treatment
      resistance. This report emphasizes importance of screening young patients with
      giant prolactinoma for MEN-1 syndrome and arranging long-term follow-up for them
      expecting variable treatment outcomes. Sri Lanka requires further studies to
      describe the genotypic-phenotypic variability of MEN-1 syndrome in this
      population.

PMID- 30186641
TI  - A Case of Phlegmonous Gastritis in a Patient with Psoriatic Arthritis on
      Infliximab.
AB  - Phlegmonous gastritis is a pyogenic infection affecting the submucosa of the
      gastric wall. Although rarely diagnosed, it remains a disease with high
      mortality. We thereby describe the case of a 42-year-old male patient known for
      psoriatic arthritis on Infliximab who was diagnosed with phlegmonous gastritis
      secondary to immunosuppressive therapy. The patient had a favourable outcome with
      a conservative treatment consisting of a 14-day course of broad antibiotherapy.

PMID- 30186642
TI  - Two Cases of gamma-Heavy Chain Disease and a Review of the Literature.
AB  - Gamma heavy chain disease (gamma-HCD) is a rare lymphoproliferative disorder
      characterised by the production of a truncated immunoglobulin heavy chain. Fewer
      than 200 cases have been reported in the literature. In some cases, gamma-HCD
      occurs with other lymphoid neoplasms. This study reports clinical, biochemical,
      haematological, and histological findings in two cases of gamma-HCD. We describe
      newer biochemical diagnostic tools (HevyLite measurement, capillary
      electrophoresis, and immunotyping) that can aid in the characterisation of gamma
      HCD. The first case is an 88-year-old woman with gamma-HCD. The second case is an
      81-year-old woman who developed gamma-HCD during treatment for Waldenstrom's
      macroglobulinemia. In the second patient, histopathology identified a separate
      clone responsible for the secretion of the gamma heavy chain. Studies on the
      clonal evolution of the disease may provide insight into therapeutic implications
      and the genomic complexity of the disease.

PMID- 30186643
TI  - Ibrutinib Treatment through Nasogastric Tube in a Comatose Patient with Central
      Nervous System Localization of Mantle Cell Lymphoma.
AB  - Nowadays, mantle cell lymphoma is considered to have one of the worst prognostic
      profiles among lymphoid malignancies. Mantle cell lymphoma rarely affects the
      central nervous system (CNS) as it represents about 0.9% of diagnosis and 4%
      among recurrent cases. Here, we present the case of a 69-year-old male patient
      who was diagnosed with mantle cell lymphoma in 2006. The patient relapsed three
      times, without affecting the CNS, then was treated accordingly, and achieved
      complete remission three times. Four years after his last complete remission,
      upon receiving his last dose of treatment, the medical team noted a rapid
      worsening of the patient's neurological status followed by a deep coma state
      causing MCL neurological recurrence by exclusion diagnosis. The patient then
      received ibrutinib via a nasogastric tube at a dose of 560 mg daily. Two days
      after receiving his last dose of ibrutinib, the patient regained full
      consciousness, and 10 days later, he was discharged from the hospital. The
      patient achieved complete remission and showed no signs of neurological damages
      for 24 months following his ibrutinib treatment. We believe that the
      administration of ibrutinib through the nasogastric tube was a determinant factor
      in this patient's remission and survival.

PMID- 30186644
TI  - A Novel STAT3 Gene Mutation Related Hyper-IgE Syndrome Misdiagnosed as
      Hidradenitis Suppurativa.
AB  - Although Hyper-IgE Syndrome (HIES) is a rare immunodeficiency disorder,
      presenting symptoms may be as common as lung and skin infections. Symptoms are
      usually nonspecific such as recurrent abscesses, folliculitis, and pneumonias
      along with skeletal abnormalities. Careful history of susceptibility to skin and
      lung infections, thorough family history, and findings on physical exam can guide
      towards the diagnosis of this often-eluded condition. Early optimization of
      therapy with prophylactic antibiotics can prevent recurrent infections and future
      complications and improve quality of life and longevity of survival. We present a
      case of a young female with Hyper-IgE Syndrome with a novel mutation in STAT 3
      gene who initially presented with long standing history of intractable skin
      abscesses being managed as Hidradenitis Suppurativa.

PMID- 30186645
TI  - Prosthetic Joint Infection from Carbapenemase-Resistant Klebsiella pneumoniae
      Successfully Treated with Ceftazidime-Avibactam.
AB  - Antimicrobial resistance in Gram-negative bacteria, particularly
      Enterobacteriaceae, has become a leading cause of morbidity and mortality and a
      serious public health concern. Gram-negative bacteria carrying extended-spectrum
      beta-lactamase (ESBL) enzymes now represent a significant proportion of all
      bacteria isolated from different countries worldwide. Furthermore, the increasing
      number of isolates carrying carbapenemases in recent years includes multidrug
      resistant (MDR), extensively drug-resistant (XDR), and pandrug-resistant (PDR)
      bacteria. Here, we describe what, to our knowledge, is the first case of a
      patient with a prosthetic joint infection from carbapenemase-resistant Klebsiella
      pneumoniae (CRKP) successfully treated with ceftazidime-avibactam in Italy.

PMID- 30186646
TI  - Clusters of Healthcare-Associated Legionnaires' Disease in Two Hospitals of
      Central Greece.
AB  - Healthcare-associated Legionnaires' disease often leads to fatal respiratory
      tract infection among hospitalized patients. In this report, three cases of
      Legionnaires' disease among patients in two different hospitals (Hospital A and
      Hospital B) were investigated. After conducting an epidemiologic and
      environmental investigation, the water distribution systems (WDSs) were
      identified as the possible source of infection, as Legionella pneumophila
      serogroup 1 (Lp1) was isolated from both clinical and environmental samples.
      Patients received aerosol therapy with nebulizers during their hospitalization.
      Based on the results of the investigation, the hospitals' infection control
      committees reviewed their policies for Legionnaires' disease prevention and
      implemented control measures focusing on using sterile fluids for aerosol
      treatments.

PMID- 30186647
TI  - A 13-Year-Old with Coexistence of Gastric Volvulus and Leprosy: A Case Report of
      Two Rare Entities.
AB  - Leprosy, or Hansen's disease, is caused by infection with Mycobacterium leprae.
      It is a rare diagnosis within the continental United States. We present the case
      of a 13-year-old immigrant from the Marshall Islands who presented with recurrent
      nausea, vomiting, and abdominal pain which are found to be due to intermittent
      gastric volvulus. Gastric volvulus is also exceedingly rare, with less than 8
      pediatric cases on average per year. During her second hospitalization for
      recurrent acute gastrointestinal issues, nonspecific skin lesions were biopsied,
      revealing infection with M. leprae. The patient did not exhibit classic symptoms
      of leprosy but did have prominent skin changes including diffuse nodules. This
      case explores the pathophysiology connecting leprosy to volvulus, discussing the
      possible role of an inflammatory response to infection in causing gastric
      volvulus. The finding of lepromatous leprosy may have been unrelated but was
      fortuitous, as early intervention will result in avoidance of debilitating
      peripheral neuropathy and eventual disfiguration from Hansen's disease. This case
      highlights the importance of considering rare causes of gastric outlet
      obstruction including gastric volvulus and of considering leprosy in the
      differential for patients with unusual skin lesions or paresthesias who have a
      history of living or traveling in endemic areas.

PMID- 30186648
TI  - Capnocytophaga Induced Acute Necrotizing and Exudative Pericarditis with Abscess
      Formation.
AB  - We present the case of a 55-year-old gentleman, with bilateral pulmonary embolism
      and a large pericardial effusion that lead to a pericardial window with
      evacuation of creamy pus. Gram stains were negative, with culture growing
      Capnocytophaga. Pathology revealed acute necrotizing and exudative changes,
      including frank abscess formation. In developed countries, pericardial abscess
      and acute pericarditis are uncommon due to availability of broad-spectrum
      antibiotics. Pericardial abscess due to Capnocytophaga is even more uncommon.

PMID- 30186649
TI  - Noninvasive Positive-Pressure Ventilation for Preeclampsia-Induced Pulmonary
      Edema: 3 Case Reports and a Literature Review.
AB  - Pulmonary edema caused by severe preeclampsia can be an indication for pregnancy
      termination. We aimed to investigate whether noninvasive positive-pressure
      ventilation (NPPV) was useful for preeclampsia-induced pulmonary edema. Three
      cases of preeclampsia-induced pulmonary edema managed with NPPV in our institute
      were reviewed retrospectively. A literature review was conducted regarding NPPV
      usage during pregnancy. NPPV was initiated at 30, 20, and 24 weeks of gestation
      in the 3 cases. In all cases, NPPV slowed the progression of pulmonary edema and
      succeeded in delaying pregnancy termination by 17 days on average. Maternal
      outcomes were positive, and no intubation was required. Between 1994 and 2017,
      there were 11 articles describing 12 cases in which NPPV was applied for
      pulmonary edema during pregnancy. However, there has been no case of NPPV
      management of preeclampsia-induced pulmonary edema thus far. Maternal and fetal
      outcomes were positive in these 12 cases. NPPV may contribute to prolonging
      pregnancy in patients with poor oxygenation due to preeclampsia-induced pulmonary
      edema. However, patients should be closely monitored, and the decision to
      intubate or terminate the pregnancy should be made without delay when the
      maternal or fetal condition worsens.

PMID- 30186650
TI  - Bicornuate Bicollis Uterus with Obstruction of the Lower Uterine Segment and
      Cervical Prolapse Complicating Pregnancy.
AB  - Congenital Mullerian duct anomalies are conditions involving the female genital
      tract. Cases of complex Mullerian duct anomalies with involvement of the renal
      system are rare. Occasionally, these cases can be associated with obstetrical
      complications. Cervical prolapse infrequently complicates pregnancy, and an
      association between uterine malformations and cervical prolapse has not been
      cited in the literature. We describe the case of a primigravid patient at 38
      weeks of gestation noted to have cervical prolapse during evaluation for
      preeclampsia and labor induction. Obstetrical ultrasound at presentation to the
      labor and delivery suite revealed a high suspicion for a bicornuate uterus. The
      patient was delivered by cesarean section due to obstruction of the lower uterine
      segment of the gravid uterus. Further evaluation post-partum revealed a
      bicornuate bicolis uterus and renal agenesis. Pregnancies in patients with
      bicornuate bicollis uterus can be complicated by obstruction of the gravid
      uterus, resulting in cervical prolapse and necessitating cesarean section.

PMID- 30186651
TI  - An Uncommon Case of Pyogenic Spondylodiscitis Caused by Gemella morbillorum.
AB  - An 81-year-old man presented with severe back pain. Magnetic resonance imaging
      detected L5/S discitis without signs of epidural abscess. Punctures of the disc
      revealed that the causative organism was Gemella morbillorum (G. morbillorum),
      which is part of the normal flora of the oral cavity and an uncommon causative
      pathogen of spondylodiscitis. The E-test method was useful for rapid
      susceptibility testing. Intravenous penicillin G treatment was effective, and the
      patient recovered without surgery.

PMID- 30186652
TI  - Sextuple Tumors in Head and Neck Area: Evidence of Field Cancerization.
AB  - Background: Field cancerization is a phenomenon in which prolonged exposure to
      carcinogens induces changes throughout the epithelium leaving the field ready for
      the appearance of premalignant or malignant lesions. These alterations can
      promote the development of multiple carcinomas and explain the appearance of
      recurrences and second primary tumors. The objective of this study was to report
      the case of a patient who developed six oral cavity tumors in five years of
      treatment and, also, demonstrate the immunohistochemical changes for p53 and Ki
      67, routinely used to assess dysplasic regions. Case Report: When altered, p53
      and Ki-67 suggest the presence of field cancers, an area with genetically altered
      cells, presenting a high risk of developing premalignant and malignant lesions.
      This phenomenon explains the recurrence of malignant neoplasms after tumor
      resections. Conclusion: In addition, early identification of potentially
      malignant lesions in cases of second primary tumors is essential for effective
      treatment and patient survival, which usually have an unwelcoming prognosis.

PMID- 30186653
TI  - Scapular Bronchogenic Cyst in a Girl Presenting as Recurrent Cellulitis: A Case
      Report and Review of the Literature.
AB  - Bronchogenic cysts are rare, congenital cysts originating from respiratory
      epithelium and typically found within the chest. Cutaneous bronchogenic cysts are
      exceedingly uncommon, with only 19 reported cases in the scapular region and
      almost exclusively occurring in male patients. Herein, we present the case of a
      female patient with recurrent cellulitis secondary to a bronchogenic cyst, which
      was diagnosed after surgical excision. We also provide a review of the literature
      to consolidate the current understanding of cutaneous scapular bronchogenic
      cysts. To our knowledge, this is the first such case reported from Canada.

PMID- 30186654
TI  - Successful Localization of the Source of Hemorrhage in Patient with Post-Whipple
      Surgery by 99mTc-Labelled Red Blood Cell Scintigraphy.
AB  - Gastrointestinal Bleeding Scintigraphy (GIBS) of 99mTc-labelled red blood cells
      is a relatively simple examination to perform, with high diagnostic accuracy and
      a relatively lower radiation dose. A positive scan can either suggest surgery
      without further investigation or can indicate angiography, a more targeted
      procedure. Whipple pancreatoduodenectomy is most often performed for tumors of
      the head of the pancreas. Pancreatoduodenectomy has 30%-40% morbidity and
      mortality, and while post-pancreatoduodenectomy hemorrhage is seen in less than
      10% of patients, it accounts for 11%-38% mortality. The role of imaging in
      patients to detect relative hemodynamic stability is essential. Computed
      tomography angiography (CTA) shows the cause, site, and nature of bleeding, while
      digital subtraction angiography (DSA) has a diagnostic as well as a therapeutic
      role. We present a patient who presented with active gastrointestinal bleeding
      (GI) bleeding after undergoing a Whipple procedure, to highlight the role of GIBS
      in the successful localization of a bleeding site and the guidance of digital DSA
      in the embolization and control of the active bleeding.

PMID- 30186655
TI  - Mass-Like Ground-Glass Opacities in Sarcoidosis: A Rare Presentation Not
      Previously Described.
AB  - Various typical and atypical imaging findings for pulmonary sarcoidosis have been
      described in the literature. Ground-glass opacities are one of the atypical
      manifestations, reported as diffuse or patchy ill-defined opacities frequently
      associated with additional findings and interstitial nodules. We performed a
      literature review to determine if our case had previously been described. The
      literature describes cases of mass-like consolidations, but there are no reports
      of mass-like ground-glass opacities. The appearance of the ground-glass opacities
      in our case is unique, appearing as discrete well-defined mass-like ground-glass
      opacities in a peribronchovascular distribution without additional parenchymal
      findings typically seen in sarcoidosis.

PMID- 30186656
TI  - Eltrombopag Improves Refractory Thrombocytopenia in a Patient with Systemic Lupus
      Erythematosus.
AB  - A 42-year-old woman with systemic lupus erythematosus (SLE) was admitted to our
      hospital for evaluation of severe thrombocytopenia. She was treated with
      steroids, intravenous cyclophosphamide, intravenous immunoglobulin, and plasma
      exchange, but her thrombocytopenia did not improve. Renal biopsy showed class IV
      S(C) + V lupus nephritis, according to the classification of the International
      Society of Nephrology/Renal Pathology Society. The PA-IgG and serum
      thrombopoietin (TPO) levels were elevated. Her thrombocytopenia responded to off
      label administration of eltrombopag, which was discontinued after 42 months. At
      18 months after stopping eltrombopag, the platelet count was 19.3 * 104/MUL.
      Eltrombopag may be a therapeutic option for SLE patients with severe
      thrombocytopenia refractory to conventional therapy.

PMID- 30186657
TI  - Laparoscopic Resection of Appendiceal Schwannoma.
AB  - Background: Schwannoma arises from Schwann's cell of the neural sheath.
      Schwannoma of the large intestine, particularly of the appendix, is rare. We
      report a case of appendiceal schwannoma resected using laparoscopic surgery. Case
      Presentation: A 75-year-old man was referred to our hospital for abdominal
      fullness and nausea since 2 months. Abdominal CT revealed a well-demarcated oval
      mass of 25 mm at the tip of the appendix. Contrast-enhanced CT revealed a lesion
      with gradually enhanced contrast from the arterial phase to the equilibrium
      phase. Abdominal US revealed a well-demarcated hypoechoic tumor. Preoperative
      diagnosis indicated appendiceal mesenchymal or neuroendocrine tumor. Ileocecal
      resection with D3 lymph node dissection was performed. Pathological and
      immunohistochemical findings confirmed the diagnosis of appendiceal schwannoma.
      Conclusions: For determining the surgical procedure of nonepithelial tumor of the
      appendix, preoperative diagnosis of mesenchymal or neuroendocrine tumors is
      required. However, appendiceal schwannoma is extremely rare, and its
      characteristic findings have not yet been established. Accumulating cases of
      appendiceal schwannomas is necessary for improving imaging diagnosis and surgical
      treatment.

PMID- 30186658
TI  - Recurrent Cardiac Myxoma Treated by Orthotopic Heart Transplantation: A Case
      Report and Literature Review of Heart Transplantation for Primary Cardiac Tumor.
AB  - Primary cardiac myxoma is the most common primary cardiac tumor. Tumor resection
      is the treatment of choice and overall long-term prognosis is good and recurrence
      is rare. This report presents a case of a young girl who presented with multiple
      recurrent cardiac myxoma. She underwent 3 sternotomy surgeries of 3 separated
      episodes of cardiac myxoma resection. On the fourth recurrence, the patient
      underwent orthotopic heart transplant. The patient tolerated the procedure well
      and is alive 6 months after the procedure with NYHA class I. We reviewed
      evidences and summarized reported cases of orthotopic heart transplant operation
      for primary cardiac tumor in the literature.

PMID- 30186659
TI  - HPLC Method for Quantification of Caffeine and Its Three Major Metabolites in
      Human Plasma Using Fetal Bovine Serum Matrix to Evaluate Prenatal Drug Exposure.
AB  - Caffeine is recognized as the first-line therapeutic agent for apnea of
      prematurity. The dosage regimen is 10 mg/kg loading dose and 2.5 mg/kg
      maintenance dose. However, the plasma concentration achieved, not always, is
      therapeutically useful. It makes necessary to increase the doses to reach plasma
      concentration up to 30 or 35 MUg/mL or even higher to attain therapeutic effect.
      To study why neonates have these differences, and whether these effects are
      linked to prenatal caffeine exposure, we had to develop an analytical method for
      an accurate measurement of caffeine and metabolites concentration. The analysis
      was carried out using fetal bovine serum (FBS) as biological matrix in a high
      performance liquid chromatography with an ultraviolet detector method. This
      method allows acceptable chromatographic resolution between analytes in 15
      minutes. It was validated and proved to be linear in the 0.1-40 ug/mL range for
      caffeine, paraxanthine, theobromine, and theophylline in the same chromatographic
      analysis. Accuracy for quality control samples for intra- and interday assays was
      ranged from 96.5 to 105.2% and 97.1 to 106.2%. Precision had CV no more than 10%
      in all concentration levels for all analytes. No differences were observed
      between quantification in human and FBS. This method was applied to quantify
      plasma drug concentration in mothers and their newborns in a Mexican northeast
      population. In our study, we confirmed self-reported caffeine maternal intake in
      85.2% (n=23); meanwhile, in their newborn's plasma, it was detected only in 78%
      (n=21). Caffeine plasma concentrations in mother and newborn had a linear
      relationship, and no differences were observed between groups (mothers versus
      children). These results suggest that our analytical method and substitution of
      biological matrix was linear, precise, and accurate for caffeine quantification
      and could be used for measuring prenatal exposure and let us to study, in the
      future, concentration differences observed during apnea clinical treatment.

PMID- 30186661
TI  - Corrigendum.
AB  - [This corrects the article DOI: 10.1177/2151459318770561.].

PMID- 30186662
TI  - A review of the disagreements in the prevalence and treatment of the tethered
      cord syndromes with chiari-1 malformations.
AB  - Background: The tethered cord syndrome (TCS) accompanying Chiari-1 (CM-1)
      malformations and the occult tethered cord syndrome (OTCS) syndrome accompanying
      the low lying cerebellar tonsil (LLCT) syndrome may be treated with sectioning of
      the filum terminale (SFT). Methods: Utilizing PubMed, we reviewed the
      neurosurgical literature to determine how frequently spinal neurosurgeons
      diagnosed the TCS (e.g., conus terminating below the normal L1-L2 disc level) on
      lumbar magnetic resonance (MR) studies in patients with CM-1 malformations [e.g.
      tonsils >5-12 mm below the foramen magnum (FM) warranting SFT]. In addition, we
      assessed how frequently spinal neurosurgeons encountered the OTCS (e.g., conus
      normally located at L1-L2 on MR) accompanying the LLCT (e.g., tonsils herniated
      <5 mm below the FM) also requiring SFT. Results: According to the neurosurgical
      literature, the incidence of TCS accompanying CM-1 requiring SFT ranged from 2.2%
      to < 6%, and up to 14%. Few studies additionally highly correlated the OCTS
      accompanying the LLCT syndrome warranting SFT. Conclusions: Given the differences
      in the literature, more studies are needed to assess the risks (complications)
      vs. benefits (improved neurological outcomes) of SFT surgery for TCS with CM-1
      and SFT for OCTS with LLCT.

PMID- 30186664
TI  - One burr-hole craniotomy: Upper retrosigmoid approach in helsinki neurosurgery.
AB  - Background: In this video-abstract, we present a one burr-hole craniotomy for the
      upper retrosigmoid approach developed in Helsinki Neurosurgery to access the
      lateral cerebellar hemisphere, the cerebellopontine angle, and lateral skull base
      (e.g. including the posterior petrous bone). This approach may be utilized to
      manage tumors of the lateral posterior fossa and to perform microvascular cranial
      nerve decompression of the V or VII cranial nerves. The upper portion of the
      vertebral-posterior cerebral artery complex, and the anterior inferior cerebellar
      artery may also be accessed with this technique. Even though the specific
      location and size of the lesion may vary, this approach accesses all mentioned
      structures with a very minimal variation. Case Description: The patient with an
      unsuspected right cerebellopontine angle metastasis from a lung cancer is placed
      in the park bench position. Spinal drainage is inserted to release 50-100 ml of
      cerebrospinal fluid. The head and upper torso are elevated so that the head is
      about 20 cm above the heart level. A single-layer skin incision is made about one
      inch behind the mastoid process; the exact cranial to caudal location of the
      incision varies depending on how high or low one has to be from the foramen
      magnum and locus of pathology. The junction of the sigmoid and the transverse
      sinus is usually located just caudal to the zygomatic line, between the zygoma
      and the external occipital protuberance, and posterior to the mastoid line that
      is running caudally through the tip of the mastoid process. Dissection with
      curved retractors creates a clean space for the craniotomy. First, a burr-hole is
      made at the posterior border of the bone flap. Two curved cuts are made towards
      the mastoid process, allowing the sigmoid sinus to be partially exposed. The bone
      is cracked after thinning the anterior border of the craniotomy. A few drill
      holes are then made for tacking-up sutures. Finally, a sinus-based dura opening
      is performed under the microscope. Conclusion: Here, we described a one burr-hole
      craniotomy that provides an excellent approach to retrosigmoid lesions.
      Videolink: http://surgicalneurologyint.com/videogallery/retrosigmoid-approach.

PMID- 30186663
TI  - One burr-hole craniotomy: Supracerebellar infratentorial paramedian approach in
      Helsinki Neurosurgery.
AB  - Background: In this video abstract, we present a one burr-hole craniotomy for the
      standard supracerebellar infratentorial (SCIT) paramedian approach developed in
      Helsinki Neurosurgery for the microsurgical management of pineal region lesions,
      tentorial meningiomas, as well as arteriovenous malformations, aneurysms, and
      intrinsic tumors of the superior surface of the cerebellum. In this regard, the
      use of praying sitting position in Helsinki Neurosurgery, which is a more
      ergonomic variant of the classic sitting position, offers several advantages such
      as lower intracranial pressure, good venous outflow, gravitational retraction,
      and straight anatomical orientation. Case Description: The patient is placed in
      sitting praying position. A straight single-layer incision is made 2-3 cm lateral
      from the midline, starting about 1 inch cranial from the inion and extending
      caudally toward the foramen magnum. Curved retractors provide a wide clean space
      for craniotomy. A burr-hole is made above the transverse sinus, which may be
      identified by its anatomic relation with superior muscle insertion line on the
      occipital bone. After detachment of the dura with blunt dissectors, a craniotomy
      around the transverse sinus and continuing to the confluens sinuum is performed
      to expose about 3 cm of the dura below the level of the transverse sinus. In case
      of an adherent dura particularly present in elderly patients, a long blunt
      flexible dissector (Yasargil dissector) is used for the detachment of the bone
      from the dura. A few drill holes are made for tack-up sutures. Finally, a
      hemostatic agent covers the transverse sinus and a sinus-based dura opening is
      performed under the microscope. Conclusion: One burr-hole craniotomy for an SCIT
      paramedian approach may represent the more efficient procedure for approaching
      the pineal region, inferior surface of the tentorium, and the superior surface of
      the cerebellum as well. Videolink:
      http://surgicalneurologyint.com/videogallery/paramedian-subocciptal-approach.

PMID- 30186660
TI  - Screening and treatment of hypertension in older adults: less is more?
AB  - Screening and treatment of hypertension is a cornerstone of cardiovascular
      disease (CVD) prevention. Hypertension causes a large proportion of cases of
      stroke, coronary heart disease, heart failure, and associated disability and is
      highly prevalent especially among older adults. On the one hand, there is robust
      evidence that screening and treatment of hypertension prevents CVD and decreases
      mortality in the middle-aged population. On the other hand, among older adults,
      observational studies have shown either positive, negative, or no correlation
      between blood pressure (BP) and cardiovascular outcomes. Furthermore, there is a
      lack of high quality evidence for a favorable harm-benefit balance of
      antihypertensive treatment among older adults, especially among the oldest-old
      (i.e., above the age of 80 years), because very few trials have been conducted in
      this population. The optimal target BP may be higher among older treated
      hypertensive patients than among middle-aged. In addition, among frail or
      multimorbid older individuals, a relatively low BP may be associated with worse
      outcomes, and antihypertensive treatment may cause more harm than benefit. To
      guide hypertension screening and treatment recommendations among older patients,
      additional studies are needed to determine the most efficient screening
      strategies, to evaluate the effect of lowering BP on CVD risk and on mortality,
      to determine the optimal target BP, and to better understand the relationship
      between BP, frailty, multimorbidity, and health outcomes.

PMID- 30186665
TI  - One burr-hole craniotomy: Subtemporal approach in helsinki neurosurgery.
AB  - Background: In this video-abstract, we present the Helsinki Neurosurgery one burr
      hole craniotomy standard subtemporal approach to the floor of the middle fossa
      and the interpeduncular space. This procedure facilitates access to the multiple
      structures; the basilar artery bifurcation, the superior cerebellar artery, or
      the P1-P2 segments of the posterior cerebral artery, and lesions located around
      the posterior clinoid process/less than 10 mm above it. Even though the specific
      location and size of the lesion may vary, this approach accesses all mentioned
      structures with very minimal variation. Case Description: The patient with a
      basilar artery bifurcation aneurysm is placed in park bench position. A spinal
      drain is inserted to release 50-100 ml of cerebrospinal fluid. Next, the skin
      incision starts in front of the tragus above the earlobe, crossing the zygomatic
      line. Inferior retraction for the craniotomy is provided by hooks and hemostatic
      Raney clips placed at the superior border of the skin flap. The zygomatic line
      represents the anatomical landmark of the floor of the middle fossa. A burr-hole
      is made at the most cranial border of the bone flap. After the detachment of the
      dura with long flexible blunt dissectors, a craniotomy is performed to expose the
      dura of the inferior temporal lobe. A few drill holes are made for tacking-up
      sutures. The dural opening is then performed based on the zygomatic line. Cutting
      and opening of the tentorium runs posterior to the tentorial insertion of the
      fourth nerve. Conclusion: The described one burr-hole craniotomy offers a more
      efficient subtemporal approach. Videolink:
      http://surgicalneurologyint.com/videogallery/subtemporal-approach-unedited/.

PMID- 30186666
TI  - One burr-hole craniotomy: Enough lateral approach to foramen magnum in helsinki
      neurosurgery.
AB  - Background: In this video-abstract, we present a one burr-hole craniotomy for the
      enough lateral approach (ELA) to the foramen magnum developed in Helsinki
      Neurosurgery, a less invasive variant of the classical far lateral approach. ELA
      does not require the resection of the occipital condyle nor the exposure of the
      extracranial/intraosseal course of the lower cranial nerves. The vertebral artery
      is not transposed and the sigmoid sinus is not skeletonized. ELA allow us to
      access lesions that are close to the level of the foramen magnum (less than 10
      mm). In this regard, low-lying vertebral aneurysms, foramen magnum meningiomas,
      or low brainstem cavernomas and intrinsic tumors are our common indications for
      this approach. Case Description: The patient with a foramen magnum meningioma is
      placed in park bench position with slight backward rotation and elevation of the
      upper body to maintain the head around 20 cm above the cardiac level. The correct
      positioning of the head requires slight forward flexion, contralateral rotation,
      and contralateral tilt to open the angle with the upper shoulder. Under
      microscopic vision, a straight incision is made behind the mastoid process
      running between the zygomatic line and 4-5 cm below to the level of the mastoid
      process. The suboccipital muscles are split with electrocoagulation while the
      vertebral artery is recognized by digital palpation. Blunt dissection with cotton
      balls is performed at the occipitocervical junction. Strong retraction maintains
      a clean space for the craniotomy. A single burr-hole is placed at the posterior
      border of the craniotomy, and a small 3 * 4 cm craniotomy is performed over the
      anterior border of the intradural origin of the vertebral artery. The anterior
      lateral border of the craniotomy is reached under visual control using a diamond
      drill. In this regard, one more burr hole opposite to the first one would be a
      tiring and difficult procedure deep inside the lateral margin of the craniotomy.
      The dura is opened based on the sigmoid sinus and cerebrospinal fluid is
      released. Finally, under high microscopic magnification, the lesion is properly
      removed. Conclusion: The described procedure may represent a more efficient
      lateral approach to the foramen magnum. Videolink:
      http://surgicalneurologyint.com/videogallery/enough-lateral-approach-for-the
      foramen-magnum/.

PMID- 30186667
TI  - Intraspinal calcinosis mimicking intervertebral disc extrusion: A clinical and
      surgical case report.
AB  - Background: Subcutaneous calcinosis is a well-recognized manifestation of
      systemic sclerosis that usually involves multiple pressure points and may also be
      found in the paraspinal or intraspinal regions. In this case, intraspinal
      calcinosis uniquely led to a severe neurological deficit. Case Description: A
      patient with severe systemic sclerosis/calcinosis exhibited left greater than
      right lower extremity radiculopathy attributed to intraspinal left-sided L4-L5
      calcinosis. On examination, the patient exhibited bilateral positive Lasegue
      signs, distal lower extremity weakness (left greater than right), and bilaterally
      decreased Achilles responses. When the magnetic resonance imaging (MRI) revealed
      a significant intracanalicular mass on the left side at the L4-L5 level, the
      patient underwent a left-sided L4-L5 decompressive laminectomy. The MRI scan 5
      years later revealed no recurrence of the calcinosis, and the patient had no
      residual neurological deficit. Conclusions: Spinal calcinosis rarely involves the
      lumbar spinal canal. Here, a patient with a large left-sided L4-L5 focus of
      intraspinal calcinosis, mimicking a disc herniation, required a laminectomy to
      resect the lesion. Lumbar calcinosis should be radiologically evaluated utilizing
      using X-ray, MRI, and computed tomography studies to adequately document the
      pathology. Patients, when symptomatic, may require surgical decompression and
      excision of these lesions.

PMID- 30186668
TI  - A rare case of intracranial teratocarcinosarcoma: Case report and review of
      literature.
AB  - Background: Teratocarcinosarcoma (TCS) is a rare malignant neoplasm with
      epithelial and mesenchymal components such as fibroblasts, cartilage, bone and
      smooth muscle. With less than 100 total reported cases, this malignant neoplasm
      is rarely encountered by neurosurgeons because it primarily involves the nasal
      cavity and paranasal sinuses. Case Description: A 55-year-old male with chronic
      frontal headaches was found to have a frontal mass with involvement of nasal
      sinus and right ethmoid sinus. The patient underwent preoperative embolization of
      tumor followed by bilateral frontal craniotomy for near total resection of the
      tumor. Patient did well postoperatively without new neurological deficits.
      Conclusion: Although cases with intracranial involvement are scarce, treatment
      with surgical resection with or without adjuvant treatments of chemotherapy and
      radiation therapy is the most widely accepted with goal for gross total
      resection. In our case, we achieved near total resection and the patient
      continues to do well without any gross neurological deficits.

PMID- 30186669
TI  - [Optical coherence tomography as a predictor of visual recovery in patients with
      pituitary macroadenomas].
AB  - Background: With pituitary macroadenomas, there is a high incidence of visual
      loss from optic pathway compression. Surgical removal of the tumor usually
      prevents progression and allows visual recovery. Our objective was to evaluate if
      optical coherence tomography (OCT) predicts visual outcomes after surgical
      decompression. Methods: Patients with pituitary macroadenomas were prospectively
      recruited between February 2015 and November 2016. We evaluated preoperative and
      postoperative visual acuity, automated perimetry, and OCT. We compared the
      results 6-12 weeks and 6-9 months after surgical removal of the tumor. Dependent
      and independent continuous variables were analyzed by Student's t-test, linear
      regression analysis, and Pearson's correlation coefficients, considering P < 0.05
      as statistically significant. Results: Visual acuity and visual field defects
      were much worse in patients with a thin preoperative retinal nerve fiber layer
      (RNFL). Both patients with normal RNFL thickness and patients with thin RNFL
      experienced significant improvement in postoperative visual perimetry 6-12 weeks
      after surgery. OCT values correlated inversely with pre- and postoperative visual
      fields, which means that, if the nerve was thicker, the visual field was better.
      Patients with a normal OCT had greater recovery because their preoperative
      perimetry values were better. The correlation between OCT values and visual field
      improvement was weak, suggesting that patients' visual fields improved after
      decompressive surgery independent of the nerve's thickness. Conclusion: The
      computerized visual field continues to be the gold standard in the evaluation of
      patients with pituitary macroadenomas with optic pathway compression. Our results
      suggest that OCT might not be an accurate predictor of visual outcomes.

PMID- 30186670
TI  - [Drilling of the subarcuate fossa to release the anterior inferior cerebellar
      artery in a surgery of a vestibular Schwannoma].
AB  - Introduction: A retrosigmoid suboccipital approach is the route most commonly
      utilized to resect vestibular schwannomas (VS). However, the anterior inferior
      cerebellar artery (AICA) usually runs adjacent to internal auditory canal nerves,
      and its course may severely impede total tumor resection. Case Report: A 38-year
      old male patient presented with presumed grade T3B VS, diagnosed by magnetic
      resonance imaging (MRI). Surgery was performed using a retrosigmoid approach,
      during which the AICA was identified to be completely covered by dural and bone
      tissue. Further drilling in the subarcuate fossa was necessary to release the
      AICI, allowing for total gross resection of the VS. No neurological deficits were
      observed postoperatively. Discussion: On rare occasions, the AICA has been
      described fixed to the dura and/or embedded within subarcuate fossal bone,
      thereby preventing removal of the intra-canalicular portion of the VS and, hence,
      total resection. However, AICA release adds to the risk of vascular injury.
      Conclusion: Injury to the AICA may cause high morbidity in patients with a VS.
      Neurosurgeons must be able to recognize and deal with certain anatomical
      configurations that place patients at particularly high risk.

PMID- 30186671
TI  - Dexmedetomidine for Sedation of Neonates with HIE Undergoing Therapeutic
      Hypothermia: A Single-Center Experience.
AB  - Hypoxic-ischemic encephalopathy (HIE) is a significant cause of morbidity and
      mortality in neonates. Therapeutic hypothermia reduces the risk of death or
      disability. Providing optimal sedation while neonates are undergoing therapeutic
      hypothermia is likely beneficial but may present therapeutic challenges. There
      are limited data describing the use of dexmedetomidine for sedation in patients
      undergoing therapeutic hypothermia. The objective of this study is to evaluate
      the efficacy and short-term safety of dexmedetomidine infusion for sedation in
      term neonates undergoing therapeutic hypothermia for HIE.

PMID- 30186672
TI  - Challenges in using CellTracker Green on foraminifers that host algal
      endosymbionts.
AB  - The uses of fluorescent microscopy and fluorescent probes, such as the
      metabolically activated probe CellTrackerTM  Green CMFDA (CTG), have become
      common in studies of living Foraminifera. This metabolic requirement, as well as
      the relatively quick production of the fluorescent reaction products, makes CTG a
      prime candidate for determining mortality in bioassay and other laboratory
      experiments. Previous work with the foraminifer Amphistegina gibbosa, which hosts
      diatom endosymbionts, has shown that the species is capable of surviving both
      acute chemical exposure and extended periods of total darkness by entering a low
      activity dormant state. This paper explores the use of CTG and fluorescent
      microscopy to determine mortality in such experiments, as well as to explore the
      physiology of dormant foraminifers. The application of CTG was found to be
      complicated by the autofluorescence of the diatom symbionts, which masks the
      signal of the CTG, as well as by interactions between CTG and propylene glycol, a
      chemical of interest known to cause dormancy. These complications necessitated
      adapting methods from earlier studies using CTG. Here we present observations on
      CTG fluorescence and autofluorescence in A. gibbosa following both chemical
      exposure and periods of total darkness. While CTG can indicate vital activity in
      dormant foraminifers, complications include underestimates of total survival and
      recovery, and falsely indicating dead individuals as live due to rapid microbial
      colonization. Nonetheless, the brightness of the CTG signal in dormant
      individuals exposed to propylene glycol supports previously published results of
      survival patterns in A. gibbosa. Observations of CTG fluorescence in individuals
      kept for extended periods in aphotic conditions indicate uptake of CTG may begin
      within 30 min of exposure to light, suggesting darkness-induced dormancy and
      subsequent recovery can occur on short time scales. These results suggest that
      CTG accurately reflects changes associated with dormancy, and can be useful in
      laboratory experiments utilizing symbiont-bearing foraminifers.

PMID- 30186673
TI  - The effect of outdoor air pollution on the risk of hospitalisation for
      bronchiolitis in infants: a systematic review.
AB  - Objective: To systematically review the evidence around the effect of ambient
      levels of particulate and gaseous pollutants, and the risk of hospitalisation
      with bronchiolitis for infants under two years of age. Design: Systematic review
      of observational epidemiological studies including cohort, time series, case
      crossover and case control study designs. Data sources: Medline, Scopus, and Web
      of Science searched to November 2017 with no language restrictions. Eligibility
      criteria: Studies investigating impact of air pollution levels on particulate
      pollutants (diameter <2.5 MUm (PM2.5) or <10 MUm (PM10) and gaseous pollutants
      (nitrogen dioxide (NO2), sulphur dioxide (SO2), carbon monoxide (CO), ozone (O3))
      on hospital admission for bronchiolitis. Main outcome measure: Risk of
      hospitalisation from bronchiolitis. Results: Eight studies were eligible for
      review. Long term exposure to PM2.5 may be associated with increased risk of
      hospitalisation for bronchiolitis. SO2 may also be associated with
      hospitalisation, but results for other pollutants are inconsistent between
      studies. In three of the five studies that showed a positive association between
      air pollutants and hospitalisation, measured concentrations were below World
      Health Organization (WHO) recommended levels. Conclusions: Certain particulate
      and gaseous pollutants may have a clinically relevant effect on hospital
      admissions for bronchiolitis in children below age two years old. Large cohort or
      time series studies are needed to examine this possible association. Protocol:
      The protocol can be found at PROSPERO (CRD42017080643).

PMID- 30186674
TI  - Addressing cultural, racial and ethnic discrepancies in guideline discordant
      gestational weight gain: a systematic review and meta-analysis.
AB  - Objective: To systematically review the literature and describe the discrepancies
      in achieving the 2009 Institute of Medicine (IOM) gestational weight gain (GWG)
      guidelines across cultures. Methods: Ten databases were searched from inception
      to April 2018. Observational cohort studies were included that examined adult
      women; reported on a measure of culture; compared cultural groups, and reported
      on GWG. Articles were broken down into papers that used the current 2009 IOM GWG
      guidelines and those that used others. A meta-analysis was conducted for studies
      using the 2009 guidelines examining the prevalence of discordant GWG across
      cultural groups. Results: The review included 86 studies. Overall, 69% of women
      experienced discordant GWG irrespective of culture. White women experienced
      excessive GWG most often, and significantly more than Asian and Hispanic women;
      Black women had a higher prevalence of excessive GWG than Hispanic and Asian
      women; however, this difference was not significant. Conclusions: The majority of
      women experience excessive GWG, with White women experiencing this most often.
      Culturally diverse GWG guidelines are needed to individualize antenatal care and
      promote optimal maternal-fetal health outcomes across cultural groups.

PMID- 30186676
TI  - NMR structure of the C-terminal domain of TonB protein from Pseudomonas
      aeruginosa.
AB  - The TonB protein plays an essential role in the energy transduction system to
      drive active transport across the outer membrane (OM) using the proton-motive
      force of the cytoplasmic membrane of Gram-negative bacteria. The C-terminal
      domain (CTD) of TonB protein is known to interact with the conserved TonB box
      motif of TonB-dependent OM transporters, which likely induces structural changes
      in the OM transporters. Several distinct conformations of differently dissected
      CTDs of Escherichia coli TonB have been previously reported. Here we determined
      the solution NMR structure of a 96-residue fragment of Pseudomonas aeruginosa
      TonB (PaTonB-96). The structure shows a monomeric structure with the flexible C
      terminal region (residues 338-342), different from the NMR structure of E. coli
      TonB (EcTonB-137). The extended and flexible C-terminal residues are confirmed by
      15N relaxation analysis and molecular dynamics simulation. We created models for
      the PaTonB-96/TonB box interaction and propose that the internal fluctuations of
      PaTonB-96 makes it more accessible for the interactions with the TonB box and
      possibly plays a role in disrupting the plug domain of the TonB-dependent OM
      transporters.

PMID- 30186678
TI  - Early-season crop mapping using improved artificial immune network (IAIN) and
      Sentinel data.
AB  - Substantial efforts have been made to identify crop types by region, but few
      studies have been able to classify crops in early season, particularly in regions
      with heterogeneous cropping patterns. This is because image time series with both
      high spatial and temporal resolution contain a number of irregular time series,
      which cannot be identified by most existing classifiers. In this study, we
      firstly proposed an improved artificial immune network (IAIN), and tried to
      identify major crops in Hengshui, China at early season using IAIN classifier and
      short image time series. A time series of 15-day composited images was generated
      from 10 m spatial resolution Sentinel-1 and Sentinel-2 data. Near-infrared (NIR)
      band and normalized difference vegetation index (NDVI) were selected as optimal
      bands by pair-wise Jeffries-Matusita distances and Gini importance scores
      calculated from the random forest algorithm. When using IAIN to identify
      irregular time series, overall accuracy of winter wheat and summer crops were 99%
      and 98.55%, respectively. We then used the IAIN classifier and NIR and NDVI time
      series to identify major crops in the study region. Results showed that winter
      wheat could be identified 20 days before harvest, as both the producer's accuracy
      (PA) and user's accuracy (UA) values were higher than 95% when an April 1-May 15
      time series was used. The PA and UA of cotton and spring maize were higher than
      95% with image time series longer than April 1-August 15. As spring maize and
      cotton mature in late August and September-October, respectively, these two crops
      can be accurately mapped 4-6 weeks before harvest. In addition, summer maize
      could be accurately identified after August 15, more than one month before
      harvest. This study shows the potential of IAIN classifier for dealing with
      irregular time series and Sentinel-1 and Sentinel-2 image time series at early
      season crop type mapping, which is useful for crop management.

PMID- 30186675
TI  - Metabolomic analysis of obesity, metabolic syndrome, and type 2 diabetes: amino
      acid and acylcarnitine levels change along a spectrum of metabolic wellness.
AB  - Background: Metabolic syndrome (MS) is a construct used to separate "healthy"
      from "unhealthy" obese patients, and is a major risk factor for type 2 diabetes
      (T2D) and cardiovascular disease. There is controversy over whether obese
      "metabolically well" persons have a higher morbidity and mortality than lean
      counterparts, suggesting that MS criteria do not completely describe physiologic
      risk factors or consequences of obesity. We hypothesized that metabolomic
      analysis of plasma would distinguish obese individuals with and without MS and
      T2D along a spectrum of obesity-associated metabolic derangements, supporting
      metabolomic analysis as a tool for a more detailed assessment of metabolic
      wellness than currently used MS criteria. Methods: Fasting plasma samples from 90
      adults were assigned to groups based on BMI and ATP III criteria for MS: (1) lean
      metabolically well (LMW; n = 24); (2) obese metabolically well (OBMW; n = 26);
      (3) obese metabolically unwell (OBMUW; n = 20); and (4) obese metabolically
      unwell with T2D (OBDM; n = 20). Forty-one amino acids/dipeptides, 33
      acylcarnitines and 21 ratios were measured. Obesity and T2D effects were analyzed
      by Wilcoxon rank-sum tests comparing obese nondiabetics vs LMW, and OBDM vs
      nondiabetics, respectively. Metabolic unwellness was analyzed by Jonckheere
      Terpstra trend tests, assuming worsening health from LMW -> OBMW -> OBMUW. To
      adjust for multiple comparisons, statistical significance was set at p < 0.005. K
      means cluster analysis of aggregated amino acid and acylcarnitine data was also
      performed. Results: Analytes and ratios significantly increasing in obesity, T2D,
      and with worsening health include: branched-chain amino acids (BCAAs), cystine,
      alpha-aminoadipic acid, phenylalanine, leucine + lysine, and short-chain
      acylcarnitines/total carnitines. Tyrosine, alanine and propionylcarnitine
      increase with obesity and metabolic unwellness. Asparagine and the
      tryptophan/large neutral amino acid ratio decrease with T2D and metabolic
      unwellness. Malonylcarnitine decreases in obesity and 3-OHbutyrylcarnitine
      increases in T2D; neither correlates with unwellness. Cluster analysis did not
      separate subjects into discreet groups based on metabolic wellness. Discussion:
      Levels of 15 species and metabolite ratios trend significantly with worsening
      metabolic health; some are newly recognized. BCAAs, aromatic amino acids, lysine,
      and its metabolite, alpha-aminoadipate, increase with worsening health. The
      lysine pathway is distinct from BCAA metabolism, indicating that biochemical
      derangements associated with MS involve pathways besides those affected by BCAAs.
      Even those considered "obese, metabolically well" had metabolite levels which
      significantly trended towards those found in obese diabetics. Overall, this
      analysis yields a more granular view of metabolic wellness than the sole use of
      cardiometabolic MS parameters. This, in turn, suggests the possible utility of
      plasma metabolomic analysis for research and public health applications.

PMID- 30186677
TI  - Evolution of pollination by frugivorous birds in Neotropical Myrtaceae.
AB  - Bird pollination is relatively common in the tropics, and especially in the
      Americas. In the predominantly Neotropical tribe Myrteae (Myrtaceae), species of
      two genera, Acca and Myrrhinium, offer fleshy, sugary petals to the consumption
      of birds that otherwise eat fruits, thus pollinating the plants in an unusual
      plant-animal interaction. The phylogenetic position of these genera has been
      problematic, and therefore, so was the understanding of the evolution of this
      interaction. Here we include new sequences of Myrrhinium atropurpureum in a
      comprehensive molecular phylogeny based on a balanced sample of two plastid and
      two nuclear markers, with the aim of providing the historical framework of
      pollination by frugivorous birds in Myrteae. We developed 13 flower and
      inflorescence characters that comprehensively depict the macroscopic
      morphological components of this interaction. Bayesian and parsimony phylogenies
      concur in placing both Acca and Myrrhinium in a clade with Psidium species; with
      Myrrhinium sister to Psidium. Mapping of morphological characters indicated some
      degree of convergence (e.g., fleshy petals, purplish display) but also
      considerable divergence in key characters that point to rather opposing
      pollination strategies and also different degrees of specialization in Acca
      versus Myrrhinium. Pollination by frugivorous birds represents a special case of
      mutualism that highlights the evolutionary complexities of plant-animal
      interactions.

PMID- 30186679
TI  - Energy cost associated with moving platforms.
AB  - Background: Previous research suggests motion induced fatigue contributes to
      significant performance degradation and is likely related to a higher incidence
      of accidents and injuries. However, the exact effect of continuous
      multidirectional platform perturbations on energy cost (EC) with experienced
      personnel on boats and other seafaring vessels remains unknown. Objective: The
      objective of this experiment was to measure the metabolic ECs associated with
      maintaining postural stability in a motion-rich environment. Methods: Twenty
      volunteer participants, who were free of any musculoskeletal or balance
      disorders, performed three tasks while immersed in a moving environment that
      varied motion profiles similar to those experienced by workers on a mid-size
      commercial fishing vessel (static platform (baseline), low and high motions
      (HMs)). Cardiorespiratory parameters were collected using an indirect
      calorimetric system that continuously measured breath-by-breath samples. Heart
      rate was recoded using a wireless heart monitor. Results: Results indicate a
      systematic increase in metabolic costs associated with increased platform
      motions. The increases were most pronounced during the standing and lifting
      activities and were 50% greater during the HM condition when compared to no
      motion. Increased heart rates were also observed. Discussion: Platform motions
      have a significant impact on metabolic costs that are both task and magnitude of
      motion dependent. Practitioners must take into consideration the influence of
      motion-rich environments upon the systematic accumulation of operator fatigue.

PMID- 30186680
TI  - Effects of mesoscale eddies on behavior of an oil spill resulting from an
      accidental deepwater blowout in the Black Sea: an assessment of the environmental
      impacts.
AB  - Because of the environmental sensitivity of the Black Sea, as a semi-enclosed
      sea, any subsea oil spill can cause destructive impacts on the marine environment
      and beaches. Employing numerical modeling as a prediction tool is one of the most
      efficient methods to understand oil spill behavior under various environmental
      forces. In this regard, a coupled circulation/deepsea oil spill model has been
      applied to the Black Sea to address the behavior of the oil plume resulting from
      a representative hypothetical deepwater blowout. With climatological forcing, the
      hydrodynamic module based on DieCAST ocean circulation model realistically
      reproduces seasonally-varying circulation from basin-scale dominant structures to
      meso- and sub-mesoscale elements. The oil spill model utilizes pre-calculated
      DieCAST thermo-hydrodynamic fields and uses a Lagrangian tracking algorithm for
      predicting the displacement of a large number of seeded oil droplets, the sum of
      which forms the rising oil plume resulting from a deepwater blowout. Basic
      processes affecting the transport, dispersal of oil and its fate in the water
      column are included in the coupled model. A hypothetical oil source was set at
      the bottom, at the northwestern edge of the Shatsky Ridge in the area east of the
      Crimea Peninsula where the oil exploration/development is likely to be planned.
      Goals of the study are to elucidate the behavior of the subsea oil plume and
      assess scales of contamination of marine environment and coastlines resulting
      from potential blowouts. The two 20-day scenarios with the oil released by a
      hypothetical blowout were examined to reveal combined effects of the basin-scale
      current, near-shore eddies, and winds on the behavior of the rising oil plume and
      its spreading on the surface. Special attention is paid to the Caucasian near
      shore anticyclonic eddy which is able to trap surfacing oil, detain it and
      deliver it to shores. The length of contaminated coastlines of vulnerable Crimean
      and Caucasian coasts are assessed along with amounts of oil beached and
      deposited.

PMID- 30186682
TI  - Anatomical notes and discussion of the first described aetosaur Stagonolepis
      robertsoni (Archosauria: Suchia) from the Upper Triassic of Europe, and the use
      of plesiomorphies in aetosaur biochronology.
AB  - Stagonolepis robertsoni, from the Late Triassic of Scotland, was the first named
      aetosaurian. Known mostly from a series of natural molds from two localities, the
      osteology of this taxon has been difficult to interpret. Detailed work on this
      material in the late 1950s resulted in a monograph that set the standard for the
      understanding of aetosaurians, making Stagonolepis robertsoni the best known
      aetosaurian; however, little has been done with this material since. Reanalysis
      of this material shows that despite its limitations the early 1960s
      reconstruction work depicts the preserved characteristics faithfully, especially
      in the skull. The first cervical rib is extremely anteroposteriorly elongate as
      in Alligator, a character not previously recognized in aetosaurians. Diapophyseal
      and zygapophyseal vertebral laminae are present in the cervical and trunk
      vertebrae. The ilium is autapomorphic with distinct pre- and post-processes of
      the iliac blade. The osteoderms differ from North and South American material
      that has been ascribed to the genus. Those assignments are based on
      plesiomorphies within Aetosauria, such as a radial ornamentation and a
      posteriorly located and medially offset dorsal eminence. Biostratigraphic
      correlations using taxonomic conclusions based on plesiomorphic characters should
      not be used. The holotype specimen of S. robertsoni is currently diagnostic, in
      part because ventral osteoderms are not known for many aetosaurian taxa and the
      surface ornamentation of randomly distributed, closely packed oblong pits found
      in S. robertsoni is unique within Aetosauria.

PMID- 30186681
TI  - Contextual and individual determinants of oral health-related quality of life
      among five-year-old children: a multilevel analysis.
AB  - Background: Contextual factors may influence oral health-related quality of life
      (OHRQoL) in children. The aim of the present study was to evaluate the influence
      of individual and contextual determinants of OHRQoL based on the perceptions of
      children. Methods: A cross-sectional study was conducted with a representative
      sample of 769 five-year-old children from public and private preschools in a city
      in the countryside of northeast Brazil. Parents/caregivers answered
      questionnaires addressing psychological aspects, sociodemographic data and
      aspects of the child's oral health. The children answered the child version of
      the Scale of Oral Health Outcomes for five-year-old children and were submitted
      to oral examinations. Variables related to the context were obtained from the
      schools and official municipal publications. Unadjusted and adjusted multilevel
      Poisson regression models were used to investigate associations between
      variables. Results: In the adjusted analysis, parent's/caregiver's schooling,
      household income, parent's/caregiver's age, a history of dental pain, dental
      caries and its consequences and traumatic dental injury were considered
      individual determinants of OHRQoL according to the children's self-reports. After
      the incorporation of the contextual determinants, the association between
      parent's/caregiver's schooling and OHRQoL lost its significance. Type of school
      was the context variable that remained associated with OHRQoL. Discussion:
      Besides the clinical and sociodemographic individual characteristics,
      characteristics of the school environment in which the child studies are
      associated with self-reported impacts on OHRQoL.

PMID- 30186683
TI  - Greenhouse gas emissions limited by low nitrogen and carbon availability in
      natural, restored, and agricultural Oregon seasonal wetlands.
AB  - Wetlands are the major natural source of the greenhouse gas methane (CH4) and are
      also potentially an important source of nitrous oxide (N2O), though there is
      considerable variability among wetland types with some of the greatest
      uncertainty in freshwater mineral-soil wetlands. In particular, trace gas
      emissions from seasonal wetlands have been very poorly studied. We measured
      fluxes of CH4, N2O, and CO2(carbon dioxide), soil nutrients, and net primary
      productivity over one year in natural, restored, and agricultural seasonal
      wetland prairies in the Willamette Valley, Oregon, USA. We found zero fluxes for
      CH4 and N2O, even during periods of extended waterlogging of the soil. To explore
      this lack of emissions, we performed a laboratory experiment to examine the
      controls over these gases. In a fully-factorial design, we amended anaerobic
      soils from all wetlands with nitrate, glucose, and NaOH (to neutralize pH) and
      measured production potentials of N2, N2O, CH4, and CO2. We found that
      denitrification and N2O production were co-limited by nitrate and carbon, with
      little difference between the three wetland types. This co-limitation suggests
      that low soil carbon availability will continue to constrain N2O emissions and
      denitrification in these systems even when receiving relatively high levels of
      nitrogen inputs. Contrary to the results for N2O, the amended wetland soils never
      produced significant amounts of CH4 under any treatment. We hypothesize that high
      concentrations of alternative electron acceptors exist in these soils so that
      methanogens are noncompetitive with other microbial groups. As a result, these
      wetlands do not appear to be a significant source or sink of soil carbon and thus
      have a near zero climate forcing effect. Future research should focus on
      determining if this is a generalizable result in other seasonal wetlands.

PMID- 30186684
TI  - Defining the short-term effects of pharmacological 5'-AMP activated kinase
      modulators on mitochondrial polarization, morphology and heterogeneity.
AB  - Background: Under aerobic growth conditions, mitochondria are the major producers
      of cellular ATP and crucial for the proper performance of organs and tissues.
      This applies especially to cells with high energy demand, such as the renal
      proximal tubule epithelium. Mitochondrial dysfunction contributes to the
      pathology of human health conditions, including various kidney diseases. The
      improvement of mitochondrial function ameliorates some of these pathologies. This
      can potentially be achieved with pharmacological compounds. For example, long
      term treatment with activators of 5'-AMP activated kinase (AMPK) enhances
      mitochondrial biogenesis. However, pharmacological damage control during acute
      cell injury requires that the short-term effects of these compounds and the
      impact on healthy cells are also understood. It was our objective to define the
      changes elicited by established modulators of AMPK activity in healthy renal
      proximal tubule cells. Methods: Our work combines confocal microscopy with
      quantitative image analysis, 3D image reconstruction and Western blotting to
      provide novel insights into the biology of mitochondria. Specifically, we
      evaluated the effects of pharmacological AMPK modulators (compound C, AICAR,
      phenformin, resveratrol) on mitochondrial polarization, morphology and
      heterogeneity. Microscopic studies generated information at the single cell and
      subcellular levels. Our research focused on LLC-PK1 cells that are derived from
      the renal proximal tubule. Mitochondrial heterogeneity was also examined in MCF7
      breast cancer cells. Results: Pharmacological agents that affect AMPK activity in
      renal proximal tubule cells can alter mitochondrial organization and the
      electrochemical potential across the inner mitochondrial membrane. These changes
      were compound-specific. Short-term incubation with the AMPK inhibitor compound C
      caused mitochondrial hyperpolarization. This was accompanied by mitochondrial
      fragmentation. By contrast, AMPK activators AICAR, phenformin and resveratrol had
      little impact. We further show that the biological properties of mitochondria are
      determined by their subcellular location. Mitochondria at the cell periphery
      displayed higher MitoTracker/Tom70 values as compared to organelles located in
      the vicinity of the nucleus. This was not limited to renal proximal tubule cells,
      but also observed in MCF7 cells. Pharmacological AMPK modulators altered these
      location-dependent properties in a compound-specific fashion. While the region
      dependent differences were enhanced with phenformin, they were ameliorated by
      resveratrol. Discussion: We evaluated the rapid changes in mitochondrial
      characteristics that are induced by pharmacological AMPK modulators. Our research
      supports the concept that pharmacological agents that target AMPK can rearrange
      mitochondrial networks at the single cell level. Collectively, these insights are
      relevant to the development of proper strategies for the short-term adjustment of
      mitochondrial performance.

PMID- 30186685
TI  - Walking and hypertension: greater reductions in subjects with higher baseline
      systolic blood pressure following six months of guided walking.
AB  - Background: The aim of the study was to assess the effects of walking on the
      blood pressure in sedentary adults with differing degrees of systolic blood
      pressure (SBP). Methods: A total of 529 subjects with SBP above 120 mmHg were
      enrolled. Blood pressure, body weight, body mass index, waist circumference and
      walking speed were determined at enrolment and after six months. Walking sessions
      were supervised by exercise physiologists. Results: The weekly walking time of
      the subjects completing the project was uniform and reached 300 minutes by the
      second month. 56% of participants completed the 6 months intervention (182 women
      59.6 +/- 9.0 years, and 114 men, 65.4 +/- 8.6 years) 27 had a baseline SBP >160
      mm Hg, 35 between 150-159, 70 between 140-149, 89 between 130-139 and 75 between
      120-129 mmHg. Following six months of supervised walking, SBP was significantly
      reduced in all subgroups (p < 0.001), with the greatest reduction (-21.3 mmHg)
      occurring in subjects with baseline SBP >160 and the smallest reduction (-2.6
      mmHg) occurring in subjects with baseline SBP of 120-129 mmHg. Diastolic blood
      pressure, body weight, body mass index and waist circumference were also
      significantly reduced following the walking intervention (p < 0.001). These
      reductions were nearly identical within the various groups. Discussion: In a
      large group of sedentary adults with varying degrees of SBP, 6 months of
      supervised walking elicited a marked reduction in systolic blood pressure with
      the largest reductions in pressure occurring in individuals with higher baseline
      SBP.

PMID- 30186686
TI  - Awareness and knowledge of Chikungunya infection following its outbreak in
      Pakistan among health care students and professionals: a nationwide survey.
AB  - Background: The World Health Organization (WHO) declares Chikungunya (CHIK)
      infection to be endemic in South Asia. Despite its first outbreak in Pakistan, no
      documented evidence exists which reveals the knowledge or awareness of healthcare
      students and workers (HCSW) regarding CHIK, its spread, symptoms, treatment and
      prevention. Since CHIK is an emergent infection in Pakistan, poor disease
      knowledge may result in a significant delay in diagnosis and treatment. The
      current study was aimed to evaluate the awareness and knowledge of CHIK among
      HCSW. Methods: A cross-sectional study was conducted among HCSW from teaching
      institutes and hospitals in seven provinces of Pakistan. We collected information
      on socio-demographic characteristics of the participants and their knowledge by
      using a 30-item questionnaire. The cumulative knowledge score (CKS) was
      calculated by correct answers with maximum score of 22. The relationship between
      demographics and knowledge score was evaluated by using appropriate statistical
      methods. Results: There were 563 respondents; mean age 25.2 +/- 5.9 years with
      female preponderance (62.5%). Of these, 319 (56.7%) were aware of CHIK infection
      before administering the survey. The average knowledge score was 12.8 +/- 4.1 (%
      knowledge score: 58.2%). Only 31% respondents had good disease knowledge while
      others had fair (36.4%) and poor (32.6%) knowledge. Out of five knowledge
      domains, domain III (vector, disease spread and transmission) and V (prevention
      and treatment) scored lowest among all i.e. percent score 44.5% and 54.1%,
      respectively. We found that socio-demographic characteristics had no influence on
      knowledge score of the study participants. Conclusion: Approximately one-half of
      participants were not aware of CHIK infection and those who were aware had
      insufficient disease knowledge. Findings of the current study underscore the dire
      need of educational interventions not only for health care workers but also for
      students, irrespective to the discipline of study.

PMID- 30186687
TI  - A simple method for data partitioning based on relative evolutionary rates.
AB  - Background: Multiple studies have demonstrated that partitioning of molecular
      datasets is important in model-based phylogenetic analyses. Commonly,
      partitioning is done a priori based on some known properties of sequence
      evolution, e.g. differences in rate of evolution among codon positions of a
      protein-coding gene. Here we propose a new method for data partitioning based on
      relative evolutionary rates of the sites in the alignment of the dataset being
      analysed. The rates are inferred using the previously published Tree Independent
      Generation of Evolutionary Rates (TIGER), and the partitioning is conducted using
      our novel python script RatePartitions. We conducted simulations to assess the
      performance of our new method, and we applied it to eight published multi-locus
      phylogenetic datasets, representing different taxonomic ranks within the insect
      order Lepidoptera (butterflies and moths) and one phylogenomic dataset, which
      included ultra-conserved elements as well as introns. Methods: We used TIGER
      rates to generate relative evolutionary rates for all sites in the alignments.
      Then, using RatePartitions, we partitioned the data into partitions based on
      their relative evolutionary rate. RatePartitions applies a simple formula that
      ensures a distribution of sites into partitions following the distribution of
      rates of the characters from the full dataset. This ensures that the invariable
      sites are placed in a partition with slowly evolving sites, avoiding the pitfalls
      of previously used methods, such as k-means. Different partitioning strategies
      were evaluated using BIC scores as calculated by PartitionFinder. Results:
      Simulations did not highlight any misbehaviour of our partitioning approach, even
      under difficult parameter conditions or missing data. In all eight phylogenetic
      datasets, partitioning using TIGER-rates and RatePartitions was significantly
      better as measured by the BIC scores than other partitioning strategies, such as
      the commonly used partitioning by gene and codon position. We compared the
      resulting topologies and node support for these eight datasets as well as for the
      phylogenomic dataset. Discussion: We developed a new method of partitioning
      phylogenetic datasets without using any prior knowledge (e.g. DNA sequence
      evolution). This method is entirely based on the properties of the data being
      analysed and can be applied to DNA sequences (protein-coding, introns, ultra
      conserved elements), protein sequences, as well as morphological characters. A
      likely explanation for why our method performs better than other tested
      partitioning strategies is that it accounts for the heterogeneity in the data to
      a much greater extent than when data are simply subdivided based on prior
      knowledge.

PMID- 30186689
TI  - Eocene Western European endemic genus Thaumastosaurus: new insights into the
      question "Are the Ranidae known prior to the Oligocene?"
AB  - Background: Amphibians, due to their ecophysiological peculiarities, have a
      physiology dependent on environmental conditions and sensitively respond to their
      changes. Here, the oldest record of the genus Thaumastosaurus is described, whose
      fossil record known exclusively from Western Europe is discussed in the scope of
      the climatic changes of 33.5-40.5 Ma. Results: In the present paper, the fossil
      remains of the genus from three localities in Switzerland (11 samples overall)
      have been studied and referred to the species Thaumastosaurus bottii. Its
      stratigraphic distribution has been revised and summarised. The studied
      localities present the stratigraphically oldest and the most eastern occurrences
      of the genus Thaumastosaurus. Eocene probable ranids (Ranidae indet./Rana sp./?
      Rana sp.) from Europe could be referred to Thaumastosaurus. Discussion: Their
      first occurrence of ranids most likely coincides with a warm phase of the global
      climate at 40 Ma, as tropical conditions were prevailing in Europe. As a result
      of the gradual cooling of the global climate, the tropical conditions in Europe
      were replaced by drier open habitats towards the latest Eocene at 34 Ma, when the
      latest occurrence of the European endemic genus Thaumastosaurus is known. Taking
      the fossil record and the climate evolution of that time into account, it can be
      concluded that Thaumastosaurus represents one of the groups among the vertebrates
      that disappeared during the large extinction event at the Eo-Oligocene
      transition, known as the Grande Coupure. The fossil finds of the genus from the
      studied localities allow to refer the previously suggested Eocene true frogs to
      the genus Thaumastosaurus, hereby stating the arrival of the true frog family
      Ranidae by the genus Pelophylax in Europe from the east at the earliest
      Oligocene.

PMID- 30186688
TI  - Rhizobacterial communities of five co-occurring desert halophytes.
AB  - Background: Recently, researches have begun to investigate the microbial
      communities associated with halophytes. Both rhizobacterial community composition
      and the environmental drivers of community assembly have been addressed. However,
      few studies have explored the structure of rhizobacterial communities associated
      with halophytic plants that are co-occurring in arid, salinized areas. Methods:
      Five halophytes were selected for study: these co-occurred in saline soils in the
      Ebinur Lake Nature Reserve, located at the western margin of the Gurbantunggut
      Desert of Northwestern China. Halophyte-associated bacterial communities were
      sampled, and the bacterial 16S rDNA V3-V4 region amplified and sequenced using
      the Illumina Miseq platform. The bacterial community diversity and structure were
      compared between the rhizosphere and bulk soils, as well as among the rhizosphere
      samples. The effects of plant species identity and soil properties on the
      bacterial communities were also analyzed. Results: Significant differences were
      observed between the rhizosphere and bulk soil bacterial communities. Diversity
      was higher in the rhizosphere than in the bulk soils. Abundant taxonomic groups
      (from phylum to genus) in the rhizosphere were much more diverse than in bulk
      soils. Proteobacteria, Firmicutes, Actinobacteria, Bacteroidetes and
      Planctomycetes were the most abundant phyla in the rhizosphere, while
      Proteobacteria and Firmicutes were common in bulk soils. Overall, the bacterial
      community composition were not significantly differentiated between the bulk
      soils of the five plants, but community diversity and structure differed
      significantly in the rhizosphere. The diversity of Halostachys caspica,
      Halocnemum strobilaceum and Kalidium foliatum associated bacterial communities
      was lower than that of Limonium gmelinii and Lycium ruthenicum communities.
      Furthermore, the composition of the bacterial communities of Halostachys caspica
      and Halocnemum strobilaceum was very different from those of Limonium gmelinii
      and Lycium ruthenicum. The diversity and community structure were influenced by
      soil EC, pH and nutrient content (TOC, SOM, TON and AP); of these, the effects of
      EC on bacterial community composition were less important than those of soil
      nutrients. Discussion: Halophytic plant species played an important role in
      shaping associated rhizosphere bacterial communities. When salinity levels were
      constant, soil nutrients emerged as key factors structuring bacterial
      communities, while EC played only a minor role. Pairwise differences among the
      rhizobacterial communities associated with different plant species were not
      significant, despite some evidence of differentiation. Further studies involving
      more halophyte species, and individuals per species, are necessary to elucidate
      plant species identity effects on the rhizosphere for co-occurring halophytes.

PMID- 30186690
TI  - Diversity and evolution of the endosymbionts of Bemisia tabaci in China.
AB  - The whitefly Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae) is a cryptic
      species complex, including members that are pests of global importance. This
      study presents a screening of B. tabaci species in China for infection by the
      primary endosymbiont, Portiera aleyrodidarum, and two secondary endosymbionts,
      Arsenophonus and Cardinium. The results showed that P. aleyrodidarum was detected
      in all B. tabaci individuals, while Arsenophonus was abundant in indigenous
      species of B. tabaci Asia II 1, Asia II 3, and China 1 but absent in the invasive
      species, Middle East-Asia Minor 1 (MEAM1); Cardinium presented in the
      Mediterranean (MED), Asia II 1 and Asia II 3 species but was rarely detected in
      the MEAM1 and China 1 species. Moreover, phylogenetic analyses revealed that the
      P. aleyrodidarum and mitochondrial cytochrome oxidase 1 (mtCO1) phylograms were
      similar and corresponding with the five distinct cryptic species clades to some
      extent, probably indicating an ancient infection followed by vertical
      transmission and subsequent co-evolutionary diversification. In contrast, the
      phylogenetic trees of Arsenophonus and Cardinium were incongruent with the mtCO1
      phylogram, potentially indicating horizontal transmission in B. tabaci cryptic
      species complex. Taken together, our study showed the distinct infection status
      of endosymbionts in invasive and indigenous whiteflies; we also most likely
      indicated the co-evolution of primary endosymbiont and its host as well as the
      potential horizontal transfer of secondary endosymbionts.

PMID- 30186691
TI  - Random forest as a generic framework for predictive modeling of spatial and
      spatio-temporal variables.
AB  - Random forest and similar Machine Learning techniques are already used to
      generate spatial predictions, but spatial location of points (geography) is often
      ignored in the modeling process. Spatial auto-correlation, especially if still
      existent in the cross-validation residuals, indicates that the predictions are
      maybe biased, and this is suboptimal. This paper presents a random forest for
      spatial predictions framework (RFsp) where buffer distances from observation
      points are used as explanatory variables, thus incorporating geographical
      proximity effects into the prediction process. The RFsp framework is illustrated
      with examples that use textbook datasets and apply spatial and spatio-temporal
      prediction to numeric, binary, categorical, multivariate and spatiotemporal
      variables. Performance of the RFsp framework is compared with the state-of-the
      art kriging techniques using fivefold cross-validation with refitting. The
      results show that RFsp can obtain equally accurate and unbiased predictions as
      different versions of kriging. Advantages of using RFsp over kriging are that it
      needs no rigid statistical assumptions about the distribution and stationarity of
      the target variable, it is more flexible towards incorporating, combining and
      extending covariates of different types, and it possibly yields more informative
      maps characterizing the prediction error. RFsp appears to be especially
      attractive for building multivariate spatial prediction models that can be used
      as "knowledge engines" in various geoscience fields. Some disadvantages of RFsp
      are the exponentially growing computational intensity with increase of
      calibration data and covariates and the high sensitivity of predictions to input
      data quality. The key to the success of the RFsp framework might be the training
      data quality-especially quality of spatial sampling (to minimize extrapolation
      problems and any type of bias in data), and quality of model validation (to
      ensure that accuracy is not effected by overfitting). For many data sets,
      especially those with lower number of points and covariates and close-to-linear
      relationships, model-based geostatistics can still lead to more accurate
      predictions than RFsp.

PMID- 30186692
TI  - Detection and phylogenetic analysis of adenoviruses occurring in a single anole
      species.
AB  - Adenoviruses (AdVs) infect a wide range of hosts, and they have undergone recent
      and ancient host transfers multiple times. In reptiles, AdVs have been found in
      many captive individuals, and have been implicated in morbidity and mortality in
      several species. Yet the pathogenicity, transmission, phylogenetic distribution,
      and source of AdVs in the environment are still unknown. We therefore chose to
      opportunistically sample deceased captive Anolis sagrei individuals that were
      collected from different populations in the Bahamas and the Cayman Islands, as
      well as fecal samples from one island population, to explore the disease dynamics
      and diversity of adenovirus infecting A. sagrei populations. We found that
      adenovirus infection was present in our captive colony at low prevalence (26%),
      and was likely not the primary cause of observed morbidity and mortality. Among
      the 10 individuals (out of 38 sampled) which tested positive for adenovirus, we
      identified four adenovirus clades, several of which are distantly related,
      despite the close relationships of the A. sagrei host populations. These results
      suggest that while adenovirus may not be highly prevalent in the wild, it is
      present at low levels across much of the range of A. sagrei. It may undergo
      frequent host switching across both deep and shallow host divergences.

PMID- 30186693
TI  - Proteomics (SWATH-MS) informed by transcriptomics approach of tropical herb
      Persicaria minor leaves upon methyl jasmonate elicitation.
AB  - Background: Jasmonic acid (JA) and its derivative, methyl JA (MeJA) are hormonal
      cues released by plants that signal defense response to curb damages from biotic
      and abiotic stresses. To study such response, a tropical herbal plant, Persicaria
      minor, which possesses pungent smell and various bioactivities including
      antimicrobial and anticancer, was treated with MeJA. Such elicitation has been
      performed in hairy root cultures and plants such as Arabidopsis and rice, yet how
      MeJA influenced the proteome of an herbal species like P. minor is unknown.
      Method: In this study, P. minor plants were exogenously elicited with MeJA and
      leaf samples were subjected to SWATH-MS proteomics analysis. A previously
      published translated transcriptome database was used as a reference proteome
      database for a comprehensive protein sequence catalogue and to compare their
      differential expression. Results: From this proteomics informed by
      transcriptomics approach, we have successfully profiled 751 proteins of which 40
      proteins were significantly different between control and MeJA-treated samples.
      Furthermore, a correlation analysis between both proteome and the transcriptome
      data sets suggests that significantly upregulated proteins were positively
      correlated with their cognate transcripts (Pearson's r = 0.677) while a weak
      correlation was observed for downregulated proteins (r = 0.147). Discussion: MeJA
      treatment induced the upregulation of proteins involved in various biochemical
      pathways including stress response mechanism, lipid metabolism, secondary
      metabolite production, DNA degradation and cell wall degradation. Conversely,
      proteins involved in energy expensive reactions such as photosynthesis, protein
      synthesis and structure were significantly downregulated upon MeJA elicitation.
      Overall protein-transcript correlation was also weak (r = 0.341) suggesting the
      existence of post-transcriptional regulation during such stress. In conclusion,
      proteomics analysis using SWATH-MS analysis supplemented by the transcriptome
      database allows comprehensive protein profiling of this non-model herbal species
      upon MeJA treatment.

PMID- 30186695
TI  - Synergy between roads and disturbance favour Bromus tectorum L. invasion.
AB  - Background: Global change produces pervasive negative impacts on biodiversity
      worldwide. Land use change and biological invasions are two of the major drivers
      of global change that often coexist; however, the effects of their interaction on
      natural habitats have been little investigated. In particular, we aimed to
      analyse whether the invasion of an introduced grass (Bromus tectorum; cheatgrass)
      along roads verges and the disturbance level in the natural surrounding habitat
      interact to influence the degree of B. tectorum invasion in the latter habitats
      in north-western Patagonia. Methods: Along six different roads, totalling
      approximately 370 km, we set two 50 m * 2 m sampling plots every 5 km (73 plots
      in total). One plot was placed parallel to the road (on the roadside) and the
      other one perpendicular to it, towards the interior of the natural surrounding
      habitat. In each plot, we estimated the B. tectorum plant density in 1 m2
      subplots placed every 5 m. In the natural habitat, we registered the vegetation
      type (grassy steppe, shrub-steppe, shrubland, and wet-meadow) and the disturbance
      level (low, intermediate, and high). Disturbance level was visually categorized
      according to different signs of habitat degradation by anthropogenic use.
      Results: B. tectorum density showed an exponential decay from roadsides towards
      the interior of natural habitats. The degree of B. tectorum invasion inside
      natural habitats was positively related to B. tectorum density on roadsides only
      when the disturbance level was low. Shrub-steppes, grassy steppes and shrublands
      showed similar mean density of B. tectorum. Wet-meadows had the lowest densities
      of B. tectorum. Intermediate and highly disturbed environments presented higher
      B. tectorum density than those areas with low disturbance. Discussion: Our study
      highlights the importance of the interaction between road verges and disturbance
      levels on B. tectorum invasion in natural habitats surrounding roads of north
      western Patagonia, particularly evidencing its significance in the invasion
      onset. The importance of invasion in road verges depends on disturbance level,
      with better conserved environments being more resistant to invasion at low levels
      of B. tectorum density along road verges, but more susceptible to road verges
      invasion at higher levels of disturbance. All the habitats except wet-meadows
      were invaded at a similar degree by B. tectorum, which reflects its adaptability
      to multiple habitat conditions. Overall, our work showed that synergies among
      global change drivers impact native environments favouring the invasion of B.
      tectorum.

PMID- 30186696
TI  - A new lower actinopterygian fish from the Upper Mississippian Bluefield Formation
      of West Virginia, USA.
AB  - The Upper Mississippian Bluefield Formation of the Mauch Chunk Group in
      southeastern West Virginia is known for its preservation of a variety of
      invertebrate taxa and early tetrapod trackways, but no lower actinopterygian
      remains have been formally described from these Carboniferous rocks. Here, the
      first lower actinopterygian fish is described from the Bluefield Formation of
      West Virginia. This fish is represented by a nearly complete articulated specimen
      with a three-dimensional snout and an unobstructed view of the gular and
      branchiostegal region. This new taxon is defined by a unique set of characters,
      which include features of the snout, circumorbital series, cheek, and operculo
      gular region. These features make this fish different and distinct from
      previously described Carboniferous fishes. Some of the morphological features of
      note include the presence of a distinct lacrimal, premaxillary, ventral rostral
      and dorsal rostral bones, a narrow infraorbital ventral to the orbit, and a large
      crescent shaped infraorbital that contacts a single dermosphenotic. There is an
      anteriorly inclined hatchet-shaped preoperculum and six small suborbital bones
      anterior to the expanded region of this bone that filling the space between the
      preoperculum, dermosphenotic, and infraorbital. Posterior to the preoperculum,
      there is a single wedge-shaped dermohyal and a series of three rectangular
      anteopercular bones. The anteopercular bones extend halfway down the anterior
      border of the rectangular operculum. A median gular, two pairs of lateral gulars,
      and at least eight branchiostegal rays are present. The heterocercal caudal fin
      is deeply cleft and inequilobate. The scales have pectinated posterior margins
      and bear diagonal ridges of ganoine. The description of this new taxon represents
      the first actinopterygian and the first vertebrate body fossil described from the
      Bluefield Formation and the second actinopterygian taxon described from the Mauch
      Chunk Group in West Virginia.

PMID- 30186694
TI  - Comparison of gene expression profiles between human erythroid cells derived from
      fetal liver and adult peripheral blood.
AB  - Background: A key event in human development is the establishment of
      erythropoietic progenitors in the bone marrow, which is accompanied by a fetal-to
      adult switch in hemoglobin expression. Understanding of this event could lead to
      medical application, notably treatment of sickle cell disease and beta
      thalassemia. The changes in gene expression of erythropoietic progenitor cells as
      they migrate from the fetal liver and colonize the bone marrow are still rather
      poorly understood, as primary fetal liver (FL) tissues are difficult to obtain.
      Methods: We obtained human FL tissue and adult peripheral blood (AB) samples from
      Thai subjects. Primary CD34+ cells were cultured in vitro in a fetal bovine serum
      based culture medium. After 8 days of culture, erythroid cell populations were
      isolated by flow cytometry. Gene expression in the FL- and AB-derived cells was
      studied by Affymetrix microarray and reverse-transcription quantitative PCR. The
      microarray data were combined with that from a previous study of human FL and AB
      erythroid development, and meta-analysis was performed on the combined dataset.
      Results: FL erythroid cells showed enhanced proliferation and elevated fetal
      hemoglobin relative to AB cells. A total of 1,391 fetal up-regulated and 329
      adult up-regulated genes were identified from microarray data generated in this
      study. Five hundred ninety-nine fetal up-regulated and 284 adult up-regulated
      genes with reproducible patterns between this and a previous study were
      identified by meta-analysis of the combined dataset, which constitute a core set
      of genes differentially expressed between FL and AB erythroid cells. In addition
      to these core genes, 826 and 48 novel genes were identified only from data
      generated in this study to be FL up- and AB up-regulated, respectively. The in
      vivo relevance for some of these novel genes was demonstrated by pathway
      analysis, which showed novel genes functioning in pathways known to be important
      in proliferation and erythropoiesis, including the mitogen-activated protein
      kinase (MAPK) and the phosphatidyl inositol 3 kinase (PI3K)-Akt pathways.
      Discussion: The genes with upregulated expression in FL cells, which include many
      novel genes identified from data generated in this study, suggest that cellular
      proliferation pathways are more active in the fetal stage. Erythroid progenitor
      cells may thus undergo a reprogramming during ontogenesis in which proliferation
      is modulated by changes in expression of key regulators, primarily MYC, and
      others including insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3),
      neuropilin and tolloid-like 2 (NETO2), branched chain amino acid transaminase 1
      (BCAT1), tenascin XB (TNXB) and proto-oncogene, AP-1 transcription factor subunit
      (JUND). This reprogramming may thus be necessary for acquisition of the adult
      identity and switching of hemoglobin expression.

PMID- 30186697
TI  - Soil properties and carbon and nitrogen pools in a young hillside longan orchard
      after the introduction of leguminous plants and residues.
AB  - The intensification of young hillside Dimocarpus longan orchard cultivation has
      led to increase soil erosion and decrease soil fertility in South China.
      Leguminous crops are often used for improving soil properties. An approximately 2
      year-long field experiment in lateritic soil in South China was conducted to
      evaluate the effects of legume introductions on soil properties and carbon (C)
      and nitrogen (N) pools. Two leguminous and one non-leguminous plant species,
      including Arachis hypogaea L. (a leguminous oilseed crop species, DA),
      Stylosanthes guianensis (a perennial herbaceous leguminous species, DS) and
      Lolium perenne L. (an annual non-leguminous forage species, DL), were introduced
      into a D. longan orchard as three treatments and compared to the monoculture of
      D. longan (the control, D0). And the harvested biomass residues of the three
      cover plants were returned to their corresponding plots as green manure. Soil
      samples were collected from depths of 0-10 and 10-20 cm approximately 2 years
      after treatment application. The results showed that, compared with D0, DA
      significantly improved the contents of soil available phosphorus, dissolved
      organic carbon (DOC), total nitrogen, ammonium and the N pool. In addition, DS
      significantly increased the contents of DOC, microbial biomass carbon and
      ammonium in the soil. However, DL did not affect any soil properties or the C and
      N pools. In addition, neither DA nor DS altered the soil bulk density or the
      contents of available nitrogen, total organic carbon and the C pool. The
      improvement of soil properties by DS and DA was positively correlated with the
      plant residues amount, plant N content but negatively correlated with the plant
      C:N ratios. Besides, the plant growth of longan was significantly improved by DA.
      In conclusion, compared with that of S. guianensis, the introduction of A.
      hypogaea L. was more helpful for restoring and improving soil properties, N pool
      and longan growth within the young hillside orchard in South China.

PMID- 30186698
TI  - Compositional and predicted functional analysis of the gut microbiota of Radix
      auricularia (Linnaeus) via high-throughput Illumina sequencing.
AB  - Due to its wide distribution across the world, the snail Radix auricularia plays
      a central role in the transferal of energy and biomass by consuming plant biomass
      in freshwater systems. The gut microbiota are involved in the nutrition,
      digestion, immunity, and development of snails, particularly for cellulolytic
      bacteria, which greatly contribute to the digestion of plant fiber. For the first
      time, this study characterized the gut bacterial communities of R. auricularia,
      as well as predicted functions, using the Illumina Miseq platform to sequence 16S
      rRNA amplicons. Both juvenile snails (JS) and adult snails (AS) were sampled. The
      obtained 251,072 sequences were rarefied to 214,584 sequences and clustered into
      1,196 operational taxonomic units (OTUs) with 97% sequence identity. The
      predominant phyla were Proteobacteria (JS: 36.0%, AS: 31.6%) and Cyanobacteria
      (JS: 16.3%, AS: 19.5%), followed by Chloroflexi (JS: 9.7%, AS: 13.1%), Firmicutes
      (JS: 14.4%, AS: 6.7%), Actinobacteria (JS: 8.2%, AS: 12.6%), and Tenericutes (JS:
      7.3%, AS: 6.2%). The phylum Cyanobacteria may have originated from the plant diet
      instead of the gut microbiome. A total of 52 bacterial families and 55 genera
      were found with >1% abundance in at least one sample. A large number of species
      could not be successfully identified, which could indicate the detection of novel
      ribotypes or result from insufficient availability of snail microbiome data. The
      core microbiome consisted of 469 OTUs, representing 88.4% of all sequences.
      Furthermore, the predicted function of bacterial community of R. auricularia
      performed by Phylogenetic Investigation of Communities by Reconstruction of
      Unobserved States suggests that functions related to metabolism and environmental
      information processing were enriched. The abundance of carbohydrate suggests a
      strong capability of the gut microbiome to digest lignin. Our results indicate an
      abundance of bacteria in both JS and AS, and thus the bacteria in R. auricularia
      gut form a promising source for novel enzymes, such as cellulolytic enzymes, that
      may be useful for biofuel production. Furthermore, searching for xenobiotic
      biodegradation bacteria may be a further important application of these snails.

PMID- 30186700
TI  - BioWorkbench: a high-performance framework for managing and analyzing
      bioinformatics experiments.
AB  - Advances in sequencing techniques have led to exponential growth in biological
      data, demanding the development of large-scale bioinformatics experiments.
      Because these experiments are computation- and data-intensive, they require high
      performance computing techniques and can benefit from specialized technologies
      such as Scientific Workflow Management Systems and databases. In this work, we
      present BioWorkbench, a framework for managing and analyzing bioinformatics
      experiments. This framework automatically collects provenance data, including
      both performance data from workflow execution and data from the scientific domain
      of the workflow application. Provenance data can be analyzed through a web
      application that abstracts a set of queries to the provenance database,
      simplifying access to provenance information. We evaluate BioWorkbench using
      three case studies: SwiftPhylo, a phylogenetic tree assembly workflow;
      SwiftGECKO, a comparative genomics workflow; and RASflow, a RASopathy analysis
      workflow. We analyze each workflow from both computational and scientific domain
      perspectives, by using queries to a provenance and annotation database. Some of
      these queries are available as a pre-built feature of the BioWorkbench web
      application. Through the provenance data, we show that the framework is scalable
      and achieves high-performance, reducing up to 98% of the case studies execution
      time. We also show how the application of machine learning techniques can enrich
      the analysis process.

PMID- 30186699
TI  - Movement and joints: effects of overuse on anuran knee tissues.
AB  - Movement plays a main role in the correct development of joint tissues. In
      tetrapods, changes in normal movements produce alterations of such tissues during
      the ontogeny and in adult stages. The knee-joint is ideal for observing the
      influence of movement disorders, due to biomechanical properties of its
      components, which are involved in load transmission. We analyze the reaction of
      knee tissues under extreme exercise in juveniles and adults of five species of
      anurans with different locomotor modes. We use anurans as the case study because
      they undergo great mechanical stress during locomotion. We predicted that (a)
      knee tissues subjected to overuse will suffer a structural disorganization
      process; (b) adults will experience deeper morphological changes than juveniles;
      and (c) morphological changes will be higher in jumpers compared to walkers. To
      address these questions, we stimulated specimens on a treadmill belt during 2
      months. We performed histological analyses of the knee of both treated and
      control specimens. As we expected, overuse caused structural changes in knee
      tissues. These alterations were gradual and higher in adults, and similar between
      jumpers and walkers species. This study represents a first approach to the
      understanding of the dynamics of anuran knee tissues during the ontogeny, and in
      relation to locomotion. Interestingly, the alterations found were similar to
      those observed in anurans subjected to reduced mobility and also to those
      described in joint diseases (i.e., osteoarthritis and tendinosis) in mammals,
      suggesting that among tetrapods, changes in movement generate similar responses
      in the tissues involved.

PMID- 30186701
TI  - Effectiveness of five personal shark-bite deterrents for surfers.
AB  - The number of shark-human interactions and shark bites per capita has been
      increasing since the 1980s, leading to a rise in measures developed to mitigate
      the risk of shark bites. Yet many of the products commercially available for
      personal protection have not been scientifically tested, potentially providing an
      exaggerated sense of security to the people using them. We tested five personal
      shark deterrents developed for surfers (Shark Shield Pty Ltd [Ocean Guardian]
      Freedom+ Surf, Rpela, SharkBanz bracelet, SharkBanz surf leash, and Chillax Wax)
      by comparing the percentage of baits taken, distance to the bait, number of
      passes, and whether a shark reaction could be observed. We did a total of 297
      successful trials at the Neptune Islands Group Marine Park in South Australia,
      during which 44 different white sharks (Carcharodon carcharias) interacted with
      the bait, making a total of 1413 passes. The effectiveness of the deterrents was
      variable, with the Freedom+ Surf affecting shark behaviour the most and reducing
      the percentage of bait taken from 96% (relative to the control board) to 40%. The
      mean distance of sharks to the board increased from 1.6 +/- 0.1 m (control board)
      to 2.6 +/- 0.1 m when the Freedom Surf+ was active. The other deterrents had
      limited or no measureable effect on white shark behavour. Based on our power
      analyses, the smallest effect size that could be reliably detected was ~15%,
      which for the first time provides information about the effect size that a
      deterrent study like ours can reliably detect. Our study shows that deterrents
      based on similar principles-overwhelming a shark's electroreceptors (the ampullae
      of Lorenzini) with electrical pulses-differ in their efficacy, reinforcing the
      need to test each product independently. Our results will allow private and
      government agencies and the public to make informed decisions about the use and
      suitability of these five products.

PMID- 30186702
TI  - Tolerance and accumulation of lithium in Apocynum pictum Schrenk.
AB  - Primarily, lithium (Li) resource development and wider application of Li-ion
      batteries result in Li pollution and concomitantly poses increasing and
      inevitable problems to environmental health and safety. However, information is
      rare about the scope of the remediation of Li contaminated soil. Apocynum venetum
      is already proved to be a Li-accumulator with high Li tolerance and accumulation
      (Jiang et al., 2014). However, it is not clear whether Apocynum pictum, another
      species of the same genus with the same uses as A. venetum, is also a Li
      accumulator. We investigated germination, growth and physiological responses of
      A. pictum to different levels of LiCl. Germination was not significantly affected
      by low Li concentration (0-100 mmol L-1). As LiCl increased from 100 to 400 mmol
      L-1, both germination percentage and index decreased gradually. For germination
      of A. pictum seeds, the critical value (when germination percentage is 50%) in
      LiCl solution was 235 mmol L-1, and the limit value (when germination percentage
      is 0%) was 406 mmol L-1. A. pictum could accumulate >1,800 mg kg-1 Li in leaves,
      and still survived under 400 mg kg-1 Li supply. The high Li tolerance of A.
      pictum during germination and growth stage was also reflected by activity of
      alpha-amylase and contents of soluble sugar, proline and photosynthetic pigments
      under different Li treatments. The bioconcentration factors (BCF) (except
      control) and translocation factors (TF) were higher than 1.0. High tolerance and
      accumulation of Li indicated that A. pictum is Li-accumulator. Therefore, this
      species could be useful for revegetation and phytoremediation of Li contaminated
      soil.

PMID- 30186703
TI  - Profiling exercise intensity during the exergame Hollywood Workout on XBOX 360
      Kinect(r).
AB  - Background: Despite the increasing popularity of exergame practice and its
      promising benefits in counteracting physical inactivity, limited research has
      been performed to document the physiological responses during an exergame
      session. This study aims (i) to investigate the responses of heart rate (HR) and
      oxygen uptake (  Methods: A total of 39 participants performed a maximal graded
      exercise test to determine maximal oxygen uptake (  Results: Heart rate and 
      Conclusion: Exergames can be classified as light to moderate exercise. Thus,
      exergames could be an interesting alternative to traditional forms of exercise.

PMID- 30186704
TI  - Plant data visualisation using network graphs.
AB  - Background: The amount of plant data such as taxonomical classification,
      morphological characteristics, ecological attributes and geological distribution
      in textual and image forms has increased rapidly due to emerging research and
      technologies. Therefore, it is crucial for experts as well as the public to
      discern meaningful relationships from this vast amount of data using appropriate
      methods. The data are often presented in lengthy texts and tables, which make
      gaining new insights difficult. The study proposes a visual-based representation
      to display data to users in a meaningful way. This method emphasises the
      relationships between different data sets. Method: This study involves four main
      steps which translate text-based results from Extensible Markup Language (XML)
      serialisation format into graphs. The four steps include: (1) conversion of
      ontological dataset as graph model data; (2) query from graph model data; (3)
      transformation of text-based results in XML serialisation format into a graphical
      form; and (4) display of results to the user via a graphical user interface
      (GUI). Ontological data for plants and samples of trees and shrubs were used as
      the dataset to demonstrate how plant-based data could be integrated into the
      proposed data visualisation. Results: A visualisation system named plant
      visualisation system was developed. This system provides a GUI that enables users
      to perform the query process, as well as a graphical viewer to display the
      results of the query in the form of a network graph. The efficiency of the
      developed visualisation system was measured by performing two types of user
      evaluations: a usability heuristics evaluation, and a query and visualisation
      evaluation. Discussion: The relationships between the data were visualised,
      enabling the users to easily infer the knowledge and correlations between data.
      The results from the user evaluation show that the proposed visualisation system
      is suitable for both expert and novice users, with or without computer skills.
      This technique demonstrates the practicability of using a computer assisted-tool
      by providing cognitive analysis for understanding relationships between data.
      Therefore, the results benefit not only botanists, but also novice users,
      especially those that are interested to know more about plants.

PMID- 30186705
TI  - Distribution of Porphyromonas gingivalis fimA and mfa1 fimbrial genotypes in
      subgingival plaques.
AB  - Background: Strains of periodontal disease-associated bacterium Porphyromonas
      gingivalis have different pathogenicity, which can be attributed to clonal
      genetic diversity. P. gingivalis typically expresses two types of fimbriae, FimA
      and Mfa1, which comprise six (I, Ib, II, III, IV, and V) and two (mfa53 and mfa70
      ) genotypes, respectively. This study was conducted to investigate the
      distribution of the two fimbrial genotypes of P. gingivalis in clinical
      specimens. Methods: Subgingival plaques were collected from 100 participants
      during periodontal maintenance therapy and examined for P. gingivalis fimbrial
      genotypes by direct polymerase chain reaction and/or DNA sequencing. We also
      analyzed the relationship between fimbrial genotypes and clinical parameters of
      periodontitis recorded at the first medical examination. Results: Both fimbrial
      types could be detected in 63 out of 100 samples; among them, fimA genotype II
      was found in 33 samples (52.4%), in which the mfa70 genotype was 1.75 times more
      prevalent than mfa53 . The total detection rate of fimA genotypes I and Ib was
      38.1%; in these samples, the two mfa1 genotypes were observed at a comparable
      frequency. In two samples positive for fimA III (3.2%), only mfa53 was detected,
      whereas in four samples positive for fimA IV (6.3%), the two mfa1 genotypes were
      equally represented, and none of fimA V-positive samples defined the mfa1
      genotype. No associations were found between clinical parameters and fimbrial
      subtype combinations. Discussion: Both P. gingivalis fimbrial types were detected
      at various ratios in subgingival plaques, and a tendency for fimA and mfa1
      genotype combinations was observed. However, there was no association between P.
      gingivalis fimbrial genotypes and periodontitis severity.

PMID- 30186706
TI  - A new species of Leptobrachium (Anura, Megophryidae) from western Thailand.
AB  - We describe a new species of the genus Leptobrachium from the Khao Laem Mountain,
      Suan Phung District, Ratchaburi Province, Tenasserim Region, western Thailand,
      based on molecular and morphological evidences. The new species, Leptobrachium
      tenasserimense sp. nov., can be distinguished from all other congeners by the
      following combination of characters: (1) adult SVL of 41.4-58.8 mm in males and
      54.7-58.6 mm in females; (2) rounded finger and toe tips; (3) relative finger
      lengths: II<IV<I<III; relative toe lengths: I<II<V<III<IV; (4) toe webbing thick
      and well developed; (5) inner metatarsal tubercle small; (6) iris bicolored,
      black ventrally and turquoise dorsally, with light blue sclera; (7) dorsum brown
      to grey with distinct darker markings edged with brown; (8) belly and limbs
      ventrally whitish with contrasting confluent black reticulations; (9) tympanum
      mostly free of dark marking; (10) narrow dark canthal stripe present; (11)
      lateral row of dark spots absent; (12) limbs dorsally with distinct dark bars;
      tibia with four to five dark transverse bars; (13) dense dark reticulation or
      large dark blotch at groin continuing to ventral and posterior sides of thighs;
      (14) femoral gland in shape of large white blotch; (15) males with single vocal
      sac, mature males lack lip spinules. Our study provides further evidence for a
      hidden biodiversity of montane areas of Tenasserim Region on the border of
      Thailand and Myanmar.

PMID- 30186708
TI  - A Rare Case of Streptococcus dysgalactiae Subsp. Dysgalactiae Human Zoonotic
      Infection.
AB  - Streptococcus dysgalactiae has two main subspecies: Streptococcus dysgalactiae
      subsp. equisimilus (SDSE) and Streptococcus dysgalactiae subsp. dysgalactiae
      (SDSD). The vast majority of human infections belonging to Streptococcus
      dysgalactiae have been associated with SDSE. There are only three cases of SDSD
      found in humans in literature. We present a case of SDSD cellulitis and
      bacteremia in a 49-year-old female patient from Houston, Texas with no major
      exposure to animals or trauma.

PMID- 30186707
TI  - Differences between motor execution and motor imagery of grasping movements in
      the motor cortical excitatory circuit.
AB  - Background: Both motor imagery (MI) and motor execution (ME) can facilitate motor
      cortical excitability. Although cortical excitability is modulated by
      intracortical inhibitory and excitatory circuits in the human primary motor
      cortex, it is not clear which intracortical circuits determine the differences in
      corticospinal excitability between ME and MI. Methods: We recruited 10 young
      healthy subjects aged 18-28 years (mean age: 22.1 +/- 3.14 years; five women and
      five men) for this study. The experiment consisted of two sets of tasks involving
      grasp actions of the right hand: imagining and executing them. Corticospinal
      excitability and short-interval intracortical inhibition (SICI) were measured
      before the interventional protocol using transcranial magnetic stimulation
      (baseline), as well as at 0, 20, and 40 min (T0, T20, and T40) thereafter.
      Results: Facilitation of corticospinal excitability was significantly greater
      after ME than after MI in the right abductor pollicis brevis (APB) at T0 and T20
      (p < 0.01 for T0, and p < 0.05 for T20), but not in the first dorsal interosseous
      (FDI) muscle. On the other hand, no significant differences in SICI between ME
      and MI were found in the APB and FDI muscles. The facilitation of corticospinal
      excitability at T20 after MI correlated with the Movement Imagery Questionnaire
      (MIQ) scores for kinesthetic items (Rho = -0.646, p = 0.044) but did not
      correlate with the MIQ scores for visual items (Rho = -0.265, p = 0.458).
      Discussion: The present results revealed significant differences between ME and
      MI on intracortical excitatory circuits of the human motor cortex, suggesting
      that cortical excitability differences between ME and MI may be attributed to the
      activation differences of the excitatory circuits in the primary motor cortex.

PMID- 30186709
TI  - Spontaneous Left Anterior Descending Artery Dissection in a Middle-Aged Woman
      with Vitamin B12 Deficiency Treated with Coronary Artery Bypass Grafting.
AB  - Spontaneous coronary artery dissection (SCAD) is one of the rarest causes of
      acute coronary syndromes, which include myocardial infarction (MI), stable and
      unstable angina, cardiogenic shock, and sudden death. The course of the disease,
      its etiology, prevalence, prognosis, and treatment remain ill-defined. Adding to
      the complexity is the fact that patients may lack typical risk factors for
      coronary heart disease. Herein, we report a case of a 42-year-old woman with
      vitamin B12 deficiency, who presented with chest pain; electrocardiography (ECG)
      findings were consistent with the acute anterior wall MI. Cardiac catheterization
      was done, which showed a very large left anterior descending (LAD) artery
      dissection.

PMID- 30186710
TI  - Early Accreta and Uterine Rupture in the Second Trimester.
AB  - The differential diagnosis of third trimester bleeding can range from placenta
      abruptia to placenta previa to uterine rupture and the placenta accreta spectrum
      (PAS). However, patients with risk factors such as multiple cesarean sections (c
      sections), advanced maternal age (AMA), grand multiparity, and single-layer
      uterine closure are at greater risk of developing these complications earlier
      than we would traditionally expect. This case recounts a 38-year-old gravida 6
      preterm 3 term 1 abortus 1 live 4 (G6P3114) at 23 weeks and five days gestational
      age (GA) with a past medical history of preterm pregnancy, pre-eclampsia, chronic
      abruptia, three previous c-sections, and low-lying placenta who presented to the
      emergency department (ED) with vaginal bleeding. Initial workup revealed placenta
      accreta and possible percreta. The patient was placed on intramuscular (IM)
      corticosteroids in anticipation of preterm delivery. As soon as the patient was
      stable, she was discharged home. She presented to a different hospital the next
      day with the same complaints. Imaging was consistent with accreta and her
      presentation with abruption. During the hospital stay, the patient went into
      threatened preterm labor (PTL). At first, we suspected preterm premature rupture
      of membranes (PPROM) due to apparent pooling of amniotic fluid in the vaginal
      canal. Upon further work up, the diagnosis was consistent with chronic abruption
      oligohydramnios sequence (CAOS). Before this could be investigated, her hospital
      course was complicated by acute abruption and Category III/nonreassuring fetal
      heart rate (FHR) tracing. The patient underwent an emergency c-section at 26
      weeks GA as well as a planned supracervical hysterectomy for desired permanent
      sterilization. During the operation, the patient suffered a postpartum hemorrhage
      (PPH) of 4500 mL. She was later discharged home on postoperative day (POD) eight.

PMID- 30186711
TI  - Zoonotic Sporotrichosis Related to Cat Contact: First Case Report from Panama in
      Central America.
AB  - A previously healthy 34-year-old man presented with a four-week-old upper arm
      injury that started with a cat scratch and progressed into painless erythematous
      nodular ascending lesions in the left upper limb. We made the diagnosis of
      sporotrichosis based on the epidemiological association of the contact with a cat
      and culture identification. Sporotrichosis is a mycosis implantation caused by
      the Sporothrix schenckii complex. We present the first Central American case of
      sporotrichosis associated with contact with a feline.

PMID- 30186712
TI  - Glomangiosarcoma Involving the Heart with an Unknown Primary Lesion.
AB  - Glomus tumors are usually benign tumors of the glomus cells with the
      immunocytochemical and structural features of smooth muscle cells. The majority
      of the cases of glomus tumors are benign but, rarely, they demonstrate malignant
      features both clinically and histologically (also known as glomangiosarcomas).
      Although glomangiosarcoma involving extracutaneous sites is uncommon, a few cases
      have been reported. A glomangiosarcoma of the heart is extremely rare due to the
      rarity of glomus bodies in the myocardium. In this case report, we present the
      case of a 31-year-old female with glomangiosarcoma involving the heart with an
      unknown primary lesion.

PMID- 30186713
TI  - Stereotactic Radiotherapy for Intramedullary Spinal Arteriovenous Malformations.
AB  - Introduction Preliminary results of stereotactic radiotherapy (SRT) for spinal
      arteriovenous malformation (AVM) in five cases are presented.  Methods Two cases
      were male and three were female. Their median age was 32 years (range: 23 to 54
      years). The spinal intramedullary AVMs were located in the cervical spine in
      three and in the thoracic spine in two. SRT with 20 Gy in four fractions was
      delivered to the nidus in every case. Results At the end of the median follow-up
      period of 5.5 years (range: 3 to 8.5 years), the neurological symptoms and signs
      were improved or unchanged as compared with before treatment, although a
      temporary adverse effect developed between a half year and one year after SRT in
      one case. The nidi were obliterated five and a half years after SRT in one case
      and three years after SRT in one. In the other three cases, the nidi were
      unchanged. Conclusion SRT with 20 Gy in four fractions was thought to be a safe
      treatment, though this study dealt with only a small number of patients with a
      short-term follow-up period.

PMID- 30186714
TI  - Integration of Next-generation Sequencing and Immune Checkpoint Inhibitors in
      Targeted Symptom Control and Palliative Care in Solid Tumor Malignancies: A
      Multidisciplinary Clinician Perspective.
AB  - The molecular characterization of solid tumor malignancies with respect to
      tumorgenesis, risk stratification, and prognostication of chemotherapeutic side
      effects is multi-faceted. Characterizing these mechanisms requires a detailed
      understanding of cytogenetics and pharmacology. In addition to the standard
      palliative care interventions that address issues such as fatigue, neuropathy,
      performance status, depression, nutrition, cachexia, anxiety, and medical ethics,
      we must also delve into individual chemotherapy side effects. Comprehending these
      symptoms is more complex with the advent of broader targeted therapies. With the
      advent and initiation of Foundation Medicine (FMI) testing, we have been able to
      tailor regimens to the individual genetics of the patient. Next-generation
      sequencing (NGS) is a bioinformatic analysis used in order to create a targeted
      effort to understand the complex genetics of a vast array of malignancies.
      Through the process known as high-throughput sequencing we, as clinicians, can
      obtain more real-time genetic data and incorporate the information into our
      reasoning process. The process involves a broad manner in which deoxyribonucleic
      acid (DNA) sequence data is obtained including genome sequencing and
      resequencing, protein-DNA or proteinomics, chromatin immunoprecipitation (ChIP)
      sequencing, ribonucleic acid (RNA) sequencing, and epigenomic analysis. High
      throughput sequencing techniques including single molecule real-time sequencing,
      ion semiconductor sequencing, pyrose sequencing, sequencing by synthesis,
      sequencing by ligation, nanopore sequencing, and chain termination (otherwise
      known as Sanger sequencing) have expanded the realm of NGS and clinicians
      options.

PMID- 30186715
TI  - Twin Reversed Arterial Perfusion Sequence: Assessing the Role of the Correct
      Imaging Modality in a Rare Clinical Entity.
AB  - Acardiac twin formation is a rare anomaly. It is one of the most extreme
      complications of monozygotic twin pregnancies. Such occurrences are brought about
      when a normal twin donates blood to an abnormal twin through its umbilical
      arteries via vascular anastomoses at the level of the placenta, which is termed
      as twin reversed arterial perfusion sequence (TRAPS). Twin reversed arterial
      perfusion sequence is considered a rare variant of twin-to-twin transfusion
      syndrome. Due to the considerable blood transfer from the healthy twin to the
      parasitic one, cardiac failure can ensue in the healthy twin. The mortality of
      the acardiac twin is 100%. We present an obstetric case of a South Asian female,
      whose serial ultrasound scans consistently displayed a heterogeneous mass,
      initially labeled a teratoma. This was postoperatively diagnosed as an acardiac
      twin due to TRAPS. Thus, we would like to highlight the importance of umbilical
      artery Doppler in the prompt diagnosis of TRAPS so timely management may be
      undertaken to prevent morbidity and/or mortality of the normal twin.

PMID- 30186716
TI  - The Value of Adding Red Cell Distribution Width to Mehran Risk Score to Predict
      Contrast-induced Acute Kidney Injury in Patients with Acute Coronary Syndrome.
AB  - BACKGROUND: Contrast-induced acute kidney injury (CI-AKI) is a relatively
      reversible cause of acute kidney injury (AKI) that occurs after radiocontrast
      media administration. It is a common complication after percutaneous coronary
      intervention, especially in patients with acute coronary syndrome (ACS). The aim
      of this study is to determine the utility of red cell distribution width (RDW) in
      predicting CI-AKI in patients with ACS and to determine the value of adding RDW
      to the Mehran risk score (MRS) on admission. METHODS: A total of 161 patients who
      presented with ST-elevation myocardial infarction (STEMI) or non-STEMI were
      identified retrospectively between January 2015 and December 2016. Patients were
      divided into two groups, those who developed CI-AKI after percutaneous coronary
      intervention (PCI) and those who did not. RESULTS: A total of 161 patients were
      analyzed. Of them, 12 developed CI-AKI (eight presented with STEMI and four
      presented with non-STEMI). RDW did not correlate with the development of CI-AKI
      (14.55 +/- 1.48 vs 14.83 +/- 1.21; p = 0.072). The areas under the receiver
      operating characteristic curves (ROCs) for RDW, MRS, and the combined model (MRS
      and RDW) for the prediction of CI-AKI were 0.721 (95% confidence interval (CI),
      0.645 to 0.788; p=0.0024), 0.885 (95% CI, 0.825 to 0.930; p<0.0001), 0.890 (95%
      CI, 0.831 to 0.933; p<0.0001), respectively. Pairwise comparisons between ROCs
      for MRS vs the combined model yielded a non-significant p-value of 0.49. This
      signifies no added benefit for RDW to MRS for predicting CI-AKI. CONCLUSION: RDW
      does not correlate with the development of CI-AKI in patients with ACS. The
      Mehran risk score remains a better indicator of CI-AKI risk assessment with no
      role for the addition of RDW to it. Further studies are needed to better assess
      predictors of CI-AKI in patients undergoing percutaneous coronary intervention.

PMID- 30186717
TI  - The Amygdala, Sleep Debt, Sleep Deprivation, and the Emotion of Anger: A Possible
      Connection?
AB  - The association of sleep with emotions has long been studied. However, not much
      has been studied about the association of sleep deprivation and sleep debt with
      the emotion of anger. In this article, we focused on the association of sleep
      with anger. The results suggest that lack of sleep - sleep deprivation and sleep
      debt - both lead to the emotion of anger. Some hints about the involvement of the
      limbic system have been found. Yet, due to a lack of a quantity of evidence, we
      suggest that more studies are conducted on the same topic to help us have a more
      in-depth exploration of the association of lack of sleep with anger.

PMID- 30186718
TI  - Violence among Adolescents in Qatar: Results from the Global School-based Student
      Health Survey, 2011.
AB  - Background Despite being a neglected issue in adolescent health, interpersonal
      violence such as physical fighting constitutes a prominent cause of physical
      injuries in adolescents. Aim We aimed to study the prevalence of physical
      fighting and its associated factors among Qatar's adolescent population. Method
      We analyzed secondary data from Qatar's Global School-based Student Health Survey
      (GSHS) 2011 to determine the prevalence as well as the associated factors of
      being engaged in a physical fight in the last 12 months. Results It was found
      that almost half of the participants (49%) were involved in a physical fight;
      mostly males (60.5%) than females (37.6%). Being bullied, smoking, and having
      parental supervision were positively associated with physical fighting (OR =
      3.97, 95% CI (3.68, 4.28); OR = 1.78, 95% CI (1.61, 1.97); OR = 1.14, 95% CI
      (1.05, 1.23), respectively). Conclusion Further behavioral research on adolescent
      violence will inform the development of youth-targeted violence prevention
      programs.

PMID- 30186719
TI  - Erythema Ab Igne and Its Relation to Spinal Pathology.
AB  - Erythema ab igne is a skin condition usually caused by abnormal exposure to heat
      in a variety of forms. While common in the past, its incidence has declined
      significantly to become a rare occurrence today. Today, we still see an odd case
      once in a while, although they have become a rarity. We describe a case of a
      young man who presented with erythema ab igne with a unique cause.

PMID- 30186720
TI  - Emergency Management of Anaphylaxis: A High Fidelity Interprofessional Simulation
      Scenario to Foster Teamwork Among Senior Nursing, Medicine, and Pharmacy
      Undergraduate Students.
AB  - Nursing, medicine, and pharmacy students have limited opportunities during their
      undergraduate programs to learn and practice together as an interprofessional
      team. This has prompted faculty at Memorial University of Newfoundland to explore
      the use of high fidelity simulated interprofessional education (HF-IPE) to help
      nursing, medicine, and pharmacy students learn about their roles, develop
      communication and collaboration skills, and foster teamwork. Research has shown
      that high fidelity simulated education can promote critical thinking, engage
      learners, improve confidence, and enhance psychomotor skills; however, there is
      limited data on the impact of HF-IPE on fostering teamwork. This technical report
      describes one HF-IPE scenario designed to foster teamwork among senior
      undergraduate nursing, medicine, and pharmacy students. The scenario is designed
      to promote an understanding of the roles of nursing, medical, and pharmaceutical
      professionals in an interprofessional team during the emergency management of an
      adult patient experiencing acute anaphylaxis. Teamwork and communication skills
      are emphasized, and students are provided with the opportunity to communicate and
      collaborate within an interprofessional healthcare team.

PMID- 30186721
TI  - Improvement in Sonographic Vasospasm Following Intravenous Milrinone in a
      Subarachnoid Hemorrhage Patient with Normal Cardiac Function.
AB  - Cerebral vasospasm and delayed cerebral ischemia are well-known complications of
      an aneurysmal subarachnoid hemorrhage (aSAH), generally occurring days to weeks
      after hemorrhagic ictus. Management strategies for these complications are
      controversial and vary in efficacy. There is a growing interest in supporting the
      use of intravenous (IV) milrinone to manage vasospasm. A 31-year-old male
      presented to the hospital after being found down outside his home. Computed
      tomography (CT) of the head and subsequent CT angiogram revealed a Fisher Grade 4
      aneurysmal subarachnoid hemorrhage (aSAH). Six hours after admission, he became
      hypotensive and his neurological examination declined. A repeat CT head showed a
      new, left frontoparietal intracerebral hemorrhage (ICH) along with increasing
      SAH. He was stabilized with vasopressors and underwent emergent decompressive
      hemicraniectomy with subsequent clipping of the aneurysm. Approximately one week
      later, transcranial Doppler (TCD) showed increasing mean flow velocities in the
      bilateral anterior and middle cerebral arteries consistent with cerebral
      vasospasm. He was treated with intravenous milrinone. Repeat TCD 6.5 hours after
      the initial TCD showed improved mean flow velocities. His cardiac function by
      echocardiogram assessment was normal. The decrease in TCD velocity following
      treatment with milrinone indicates an improvement in the cerebral vasospasm
      regardless of cardiac output in a patient with subarachnoid hemorrhage. This case
      suggests that augmenting cardiac output may not be the only mechanism for the
      therapeutic benefit of milrinone.

PMID- 30186722
TI  - Evaluation of Factors which Influence Mortality in Gram-positive Bacteremia in
      Hemodialysis Patients.
AB  - Vascular access infection is one of the major contributors to hemodialysis (HD)
      patient morbidity and mortality. There is a paucity of consensus guidelines on
      vancomycin use in the HD population. The primary objective of this study was to
      determine if vancomycin serum concentrations were associated with positive
      outcomes in HD patients with Gram-positive bacteremia. A retrospective cohort
      study conducted at a 443-bed tertiary teaching county hospital from January 1,
      2010 to January 1, 2016 was performed. Patients aged 18-89, with chronic renal
      failure on hemodialysis who presented with positive blood cultures with Gram
      positive bacteria and received intravenous vancomycin for at least 24 hours were
      evaluated. A multivariate analysis was utilized comparing factors related to
      outcomes including Simplified Acute Physiology Score II (SAPS II), loading dose,
      30-day mortality and vancomycin serum concentrations. A total of 139 patients
      were obtained, 90 of whom had documented pre-dialysis serum vancomycin
      concentrations. A multivariate analysis showed that a lower SAPS II score [OR
      1.220 (95% CI: 1.086-1.370, p < 0.0001)], a higher loading dose/kg [OR 0.7911
      (0.6302-0.9929, p = 0.0239)], and pre-dialysis concentrations between 15 and 20
      mcg/mL [0.05437 (95% CI: 0.0033-0.8891, p = 0.0099)] were associated with
      decreased mortality (overall multivariate model, p < 0.0001). When patient acuity
      and loading dosing are taken into account, pre-dialysis vancomycin serum
      concentrations between 15 and 20 mcg/mL were associated with decreased mortality
      in Gram-positive bacteremic intermittent HD patients. Further prospective studies
      are needed to assess whether targeting a pre-dialysis serum vancomycin
      concentration of 15-20 mcg/mL can improve mortality.

PMID- 30186723
TI  - Ruptured Distal Superior Cerebellar Artery Dissecting Aneurysm Treated with a
      Flow-diverting Device: Case Report and Review of Literature.
AB  - Distal fusiform aneurysms of the superior cerebellar artery (SCA) are rare and
      present several challenges to clinicians, especially when ruptured. While several
      treatment options are available, including surgical clipping and endovascular
      coiling, numerous challenges still remain due to the presence of vital
      neighboring neurovascular structures. In addition, the complications that arise
      due to the compromise of brainstem perforators make these aneurysms difficult to
      treat. This case report demonstrates the successful treatment of a ruptured
      fusiform aneurysm of the SCA with a flow-diverting device. We also conducted a
      literature review of the use of flow-diverting devices for treating such
      aneurysms. When choosing a treatment modality for a ruptured aneurysm, clinicians
      must consider both the patient-specific variables as well as aneurysm morphology.
      Treatment options including microsurgical clipping, endovascular coiling, and
      flow diversion carry risks. Therefore, the clinician must decide which option
      best fits each situation.

PMID- 30186724
TI  - The Anti-vaccination Movement: A Regression in Modern Medicine.
AB  - There have been recent trends of parents in Western countries refusing to
      vaccinate their children due to numerous reasons and perceived fears. While
      opposition to vaccines is as old as the vaccines themselves, there has been a
      recent surge in the opposition to vaccines in general, specifically against the
      MMR (measles, mumps, and rubella) vaccine, most notably since the rise in
      prominence of the notorious British ex-physician, Andrew Wakefield, and his
      works. This has caused multiple measles outbreaks in Western countries where the
      measles virus was previously considered eliminated. This paper evaluates and
      reviews the origins of the anti-vaccination movement, the reasons behind the
      recent strengthening of the movement, role of the internet in the spread of anti
      vaccination ideas, and the repercussions in terms of public health and safety.

PMID- 30186725
TI  - Safest Time to Resume Oral Anticoagulation in Patients with Traumatic Brain
      Injury.
AB  - OBJECTIVE:  There is no standard protocol to guide the optimal time to resume
      anti-clotting agents after traumatic brain injury (TBI) in patients with a
      continued indication for anticoagulation/antiplatelet therapy (AAT). This study
      develops baseline data supporting a future prospective cohort study. We predict
      that there will be significantly decreased adverse events when AAT is started on
      or after Day 7. METHODS:  A retrospective chart review of 256 patients was
      performed. Patients admitted to a level I trauma center in West Texas between
      January 1, 2009, and December 31, 2012, on anti-clotting agents (specifically
      acetylsalicylic acid, coumadin, and/or clopidogrel) and who suffered a TBI were
      included. Patient metrics included admission coagulation studies, type of TBI and
      treatment, and time to continuation of AAT. Outcomes were assessed using follow
      up appointment data. The primary outcome was death (mortality). Secondary
      outcomes included myocardial infarction, stroke, re-bleed, venous
      thromboembolism, and pneumonia. RESULTS: A total of 256 patients met the
      inclusion criteria. However, only 85 patients on AAT presented for the six-month
      follow-up. Time to AAT resumption varied from immediate to 31 days. Out of the 85
      patients, 32 patients never resumed AAT, 32 patients were restarted on AAT
      medication in less than seven days, 10 patients restarted medication between
      seven and 14 days, and 11 patients restarted AAT in more than 14 days. Adverse
      events occurred most infrequently in the AAT group resuming therapy between seven
      and 14 days (10%). Adverse events were most prevalent in the AAT group that never
      resumed therapy (68.8%). CONCLUSION:  While most studies suggest that the safest
      time for resuming AAT lies between three and 10 days, our study revealed that
      adverse events were minimized in patients on AAT between seven and 9.5 days.

PMID- 30186726
TI  - Postgraduate medical education in Japan: Missed opportunity for learning clinical
      reasoning.

PMID- 30186727
TI  - Participatory research-A modernizing science for primary health care.
AB  - Participatory research is the science of partnerships underlying research,
      concerned with research governance, ownership of research products, and
      relationships behind research objectives and methods. The common strand behind
      the quite different schools of participatory research is that research should be
      in respectful partnership with people; it is not about researchers working on,
      for, or about people. Modern participatory research embraces different
      philosophies through several applications. The first application addresses
      research objectives, with participation at different points in the research
      cycle. Second, modern participatory research is relevant in adaptive management,
      including management of primary health care. Third, participatory research is a
      tool for patient engagement and patient-centered outcomes in the clinical
      context. A fourth application is participatory research as an intervention:
      Participatory research moves people, and it mobilizes resources and can thus be
      pivotal to sustainability and for health-promoting intersectoral linkages. As
      primary health care is a family medicine responsibility, participatory research
      offers family medicine a valuable toolbox complementing the accepted clinical
      toolboxes. Through shared identification of problems and decisions about
      solutions, participatory research increases participant capacity to identify and
      address their own issues. Among clinicians, it enhances professional practices.
      In the bigger social picture, all this promotes social justice, self
      determination, and knowledge utilization.

PMID- 30186728
TI  - A comparison of pneumonia care quality between general physicians and
      pulmonologists.
AB  - Background: We compared the quality of care for nursing- and healthcare
      associated pneumonia (NHCAP) and aspiration pneumonia provided by general
      physicians and pulmonologists. Methods: Questionnaires were mailed to 2490
      medical facilities across Japan. The questionnaire assessed participants'
      implementation of microbiological investigations for NHCAP or aspiration
      pneumonia, as well as steps taken to prevent pneumonia recurrence (eg, use or
      discontinuation of drugs associated with swallowing and administration of
      pneumococcal polysaccharides). Survey results were statistically compared between
      the two groups using chi-square tests. Results: We received responses from 350
      hospitals; of those, medical care for aspiration pneumonia was provided by
      pulmonologists at 190 hospitals and by general physicians at 79 hospitals. No
      significant differences were observed between the two groups of physicians for
      any of the items regarding proactive microbiological investigations or measures
      for preventing pneumonia recurrence. However, general physicians tended to be
      more proactive in conducting Gram's stains for sputum, sputum culture
      inspections, and blood culture tests. They also were more likely to implement
      measures for preventing pneumonia recurrence such as striving to increase
      patients' consciousness levels, reducing medication doses, and discontinuing
      drugs that cause difficulty with swallowing (response rates of "is done in nearly
      all cases" were 73.4%, 88.6%, 36.7%, 35.4%, and 40.5%, respectively).
      Conclusions: The quality of care provided by general physicians may be on par
      with pulmonologists in terms of proactive microbiological investigations and
      preventing pneumonia recurrence.

PMID- 30186729
TI  - Enterovaginal and colovesical fistulas as late complications of pelvic
      radiotherapy.
AB  - A 72-year-old Japanese woman presented with a fever, diarrhea, intermittent
      spotting, and constant fluid discharge from the vagina. Imaging studies revealed
      an enterovaginal fistula. She underwent radical hysterectomy and radiotherapy 35
      years previously. She also had a surgical history of nephrostomy, nephrectomy,
      ileoascending anastomosis, and colostomy. As bleeding from the enterovaginal
      fistula was uncontrollable, ileocecal resection was performed. However, a
      colovesical fistula with urinary tract infection occurred 3 months later. The
      present case indicates that fistula formation occurs and causes various symptoms
      in patients who underwent postpelvic radiotherapy, particularly in those with
      prior surgeries in the irradiated field.

PMID- 30186730
TI  - Thyroid follicular carcinoma in a teenager: A case report.
AB  - A 19-year-old girl complained of an enlarged cervical mass. Based on clinical and
      cytological assessments, it was diagnosed as thyroid follicular carcinoma and
      left thyroidectomy was performed. Although thyroid neoplasms are rare in young
      people, differentiation is needed when the rapid growth of a goiter is detected.

PMID- 30186731
TI  - Gallstone ileus with spontaneous evacuation: A case report.
AB  - A 65-year-old man was referred to our hospital for abdominal pain. He had a
      history of enterotomy with stone extraction for gallstone ileus. On abdominal
      computed tomography, a stone measuring 32 * 28 mm lodged in the jejunum was
      identified. He was diagnosed with gallstone ileus and treated using a nasal ileus
      tube. Four days after admission, computed tomography showed that the stone had
      passed into the rectum. The gallstone was spontaneously evacuated on the same
      day. A fistula with the gallbladder was found in the duodenal bulb. The patient's
      condition improved, and he was discharged 9 days after admission.

PMID- 30186732
TI  - Diffuse redness in linked color imaging is useful for diagnosing current
      Helicobacter pylori infection in the stomach.
AB  - Esophagogastroduodenoscopic examination shows diffuse redness of the mucosa of
      the gastric body, which can be identified as a deep reddish color. The present
      case underscores the importance of diffuse redness as a key endoscopic feature
      that enables prompt diagnosis of current Helicobacter pylori infection.

PMID- 30186733
TI  - Publication rate of abstracts presented at the American College of Physicians
      Japan Chapter Annual Meetings (2013-2014): A retrospective observational study.
AB  - Background: Few studies have evaluated the publication rate of abstracts
      presented at Japanese medical specialty meetings. Methods: A retrospective
      observational study was conducted to determine the publication rate of abstracts
      presented at the American College of Physicians Japan Chapter Annual Meetings
      (2013-2014). Publication rates were determined by searching the MEDLINE database
      for full-text articles. Results: Of the 116 abstracts evaluated, 14 (12.1% [95%
      CI 6.1%-18.1%]) were subsequently published in peer-reviewed journals indexed in
      the MEDLINE database. Conclusion: Further studies to investigate the barriers to
      publication among Japanese investigators and additional efforts to improve this
      low publication rate are needed.

PMID- 30186734
TI  - The mediastinal width on supine anteroposterior chest radiographs.

PMID- 30186735
TI  - Japan can learn from the Swedish primary care doctor fostering system.

PMID- 30186736
TI  - The Chirality Chain in Valine: How the Configuration at the Calpha Position
      through the O cis C'CalphaN Torsional System Leads to Distortion of the Planar
      Group CalphaC'(O cis )O trans to a Flat Tetrahedron.
AB  - Solid-state structures, based on a Cambridge Structural Database (CSD) search,
      show that there is a CalphaN/C'O cis attraction in the torsional system O cis
      C'CalphaN of valine, causing a chirality chain. The Calpha configuration controls
      the chirality of the rotation around the C'-Calpha bond, which in turn induces a
      distortion of the planar unit CalphaC'(O)O to a flat asymmetric tetrahedron.
      Conformational "reactions" take place in an energy profile with respect to
      clockwise and counterclockwise rotation around the C'-Calpha bond as well as
      stretching and flattening of the tetrahedron. The molecular property CalphaN/C'O
      cis attraction of valine is maintained in its di- and tripeptides.

PMID- 30186737
TI  - Adult Granulosa Cell Tumors of the Ovary: A Retrospective Study of 36 FIGO Stage
      I Cases with Emphasis on Prognostic Pathohistological Features.
AB  - Objective: Adult granulosa cell tumors (AGCTs) represent 2%-5% of all ovarian
      malignancies. The aim of this study was to analyze clinical and pathohistological
      parameters and their impact on recurrence, overall, and disease-free survival in
      FIGO stage I AGCT patients. Methods: The tumor specimens analyzed in this
      retrospective study were obtained from a total of 36 patients with diagnosis of
      ovarian AGCT surgically treated at the Department of Gynecology, Rijeka
      University Hospital Centre, between 1994 and 2012. Clinical, pathological, and
      follow-up data were collected. Results: The mean age at diagnosis was 54.5 years
      with a range of 24-84. The majority of the patients, 30 (83%), were in FIGO stage
      IA, 3 (8%) in stage IC1, 1 (3%) in stage IC2, and 2 (6%) in stage IC3. During
      follow-up period (median 117.5 months, range 26-276), recurrence occurred in 4
      patients (12%) with 2 deaths of the disease recorded. In univariate analysis, the
      5-year survival rates were significantly shorter in patients with FIGO substage
      IC (p = 0.019), with positive LVSI (p = 0.022), with presence of necrosis (p =
      0.040), and with hemorrhage (p = 0.017). In univariate analysis, the 5-year
      disease-free survival rates were significantly shorter in patients treated with
      fertility surgery (p = 0.004), with diffuse growth pattern (p = 0.012), with
      moderate and severe nuclear atypia (p = 0.032), and with presence of hemorrhage
      (p = 0.022). FIGO substage IC proved to be independent predictor for recurrence
      (OR = 16.87, p = 0.015, and OR = 23.49, p = 0.023, resp.) and disease-free
      survival (p = 0.0002; HR 20.84, p = 0.02) at the uni- and multivariate analyses.
      Conclusions: FIGO substage IC is predictive of recurrence and disease-free
      survival in patients with early-stage AGCTs. LVSI, presence of necrosis and
      hemorrhage, diffuse growth pattern, and nuclear atypia in AGCTs seem to be
      associated with overall and disease-free survival, so these pathological features
      should be taken into consideration when managing patients with AGCT.

PMID- 30186738
TI  - Comprehensive evaluation of male health in four communities in rural Honduras.
AB  - PODEMOS (Partnership for Ongoing Developmental, Educational and Medical Outreach
      Solutions) has been a long-standing healthcare provider in 4 communities in
      northern rural Honduras. In this study, we sought to understand and quantify the
      health challenges faced by men in the rural communities served by PODEMOS in
      order to improve the way PODEMOS delivers healthcare. Between June and July of
      2015, we conducted 104 structured survey interviews with men 18 years and older
      in rural Honduras. We found that most men face significant economic limitations
      in their ability to pay for healthcare and health-determining services and due to
      low formal education levels face health literacy challenges. Furthermore, we
      found that a quarter are at risk for health problems due to smoking, and the
      majority are at risk for musculoskeletal problems due to work in strenuous
      outdoor labor. However, we found that zero respondents drank alcohol heavily,
      which is defined as more than 14 drinks in one week. Lastly, we found varying
      opinions on female contraception use. Our findings indicate that medical brigades
      to the developing world should understand and quantify the relevant health
      challenges faced by their target populations.

PMID- 30186739
TI  - Who goes where? The importance of peer groups on attainment and the student use
      of the lecture theatre teaching space.
AB  - Understanding how students interact and learn within the lecture theatre
      environment is central to successful learning outcomes. Previous studies into the
      use of the lecture theatre teaching space have found that students sit in
      specific locations due to a range of factors; these include being noticed,
      addressing anxiety or an ability to focus. This study further explores the
      personal and social factors at play within students' lecture theatre seating
      choice and the resulting effects on attainment. Student responses on seating
      preferences detailing why they chose a given location were mapped at a seat
      specific level and correlated against attainment. In parallel, staff perceptions
      of student attainment in relation to their seating choice were obtained. No
      direct correlation between student location and attainment was found, contrary to
      staff perceptions. Interestingly, it was found that students physically locate
      into friendship groups clusters and that these clusters obtained similar levels
      of attainment in problem-solving tasks, with pockets of both high- and low
      performing students being observed. It was also noted that isolated students
      performed less well. These data would indicate that peer group formation exerts a
      strong impact on attainment and engagement. Outcomes from this study will enable
      academic staff to better understand the student body and inform the way in which
      teaching sessions are performed within a lecture theatre.

PMID- 30186740
TI  - Crystal structure of the retroviral protease-like domain of a protozoal DNA
      damage-inducible 1 protein.
AB  - DNA damage-inducible 1 (Ddi1) is a multidomain protein with one of the domains
      being retropepsin-like. HIV-1 protease inhibitors were found to reduce
      opportunistic infections caused by pathogens like Leishmania and Plasmodium, and
      some of them were shown to inhibit the growth of these parasites. In Leishmania,
      Ddi1 was identified as a likely target of the inhibitors. We report the crystal
      structure of the retropepsin-like domain of Ddi1 from Leishmania major as a dimer
      with clear density for the critical 'flap' region. We have characterized binding
      with one of the HIV-1 protease inhibitors in solution using bio-layer
      interferometry and by docking. Further, we have performed molecular dynamics (MD)
      simulation studies that show that the protein undergoes a conformational change
      from open to semi-open and closed forms with the closing of the flexible flap
      over the active site.

PMID- 30186741
TI  - Elastin molecular aging promotes MDA-MB-231 breast cancer cell invasiveness.
AB  - Elastin is a long-lived extracellular matrix protein responsible for the
      structural integrity and function of tissues. Breast cancer elastosis is a
      complex phenomenon resulting in both the deposition of elastotic masses and the
      local production of elastin fragments. In invasive human breast cancers, an
      increase in elastosis is correlated with severity of the disease and age of the
      patient. Elastin-derived peptides (EDPs) are a hallmark of aging and are
      matrikines - matrix fragments having the ability to regulate cell physiology.
      They are known to promote processes linked to tumor progression, but their
      effects on breast cancer cells remain unexplored. Our data show that EDPs enhance
      the invasiveness of MDA-MB-231 breast cancer cells through the engagement of
      matrix metalloproteases 14 and 2. We therefore suggest that elastosis and/or an
      aged stroma could promote breast cancer cell invasiveness.

PMID- 30186742
TI  - Off-target inhibition by active site-targeting SHP2 inhibitors.
AB  - Due to the involvement of SHP2 (SH2 domain-containing protein-tyrosine
      phosphatase) in human disease, including Noonan syndrome and cancer, several
      inhibitors targeting SHP2 have been developed. Here, we report that the commonly
      used SHP2 inhibitor NSC-87877 does not exhibit robust inhibitory effects on
      growth factor-dependent MAPK (mitogen-activated protein kinase) pathway
      activation and that the recently developed active site-targeting SHP2 inhibitors
      IIB-08, 11a-1, and GS-493 show off-target effects on ligand-evoked
      activation/trans-phosphorylation of the PDGFRbeta (platelet-derived growth factor
      receptor beta). GS-493 also inhibits purified human PDGFRbeta and SRC in vitro,
      whereas PDGFRbeta inhibition by IIB-08 and 11a-1 occurs only in the cellular
      context. Our results argue for extreme caution in inferring specific functions
      for SHP2 based on studies using these inhibitors.

PMID- 30186743
TI  - Identification of inactive conformation-selective interleukin-2-inducible T-cell
      kinase (ITK) inhibitors based on second-harmonic generation.
AB  - Many clinically approved protein kinase inhibitors stabilize an inactive
      conformation of their kinase target. Such inhibitors are generally highly
      selective compared to active conformation inhibitors, and consequently, general
      methods to identify inhibitors that stabilize an inactive conformation are much
      sought after. Here, we have applied a high-throughput, second-harmonic generation
      (SHG)-based conformational approach to identify small molecule stabilizers of the
      inactive conformation of interleukin-2-inducible T-cell kinase (ITK). A single
      site cysteine mutant of the ITK kinase domain was created, labeled with an SHG
      active dye, and tethered to a supported lipid bilayer membrane. Fourteen tool
      compounds, including stabilizers of the inactive and active conformations as well
      as nonbinders, were first examined for their effect on the conformation of the
      labeled ITK protein in the SHG assay. As a result, inactive conformation
      inhibitors were clearly distinguished from active conformation inhibitors by the
      intensity of SHG signal. Utilizing the SHG assay developed with the tool
      compounds described above, we identified the mechanism of action of 22 highly
      selective, inactive conformation inhibitors within a group of 105 small molecule
      inhibitors previously identified in a high-throughput biochemical screen. We
      describe here the first use of SHG for identifying and classifying inhibitors
      that stabilize an inactive vs. an active conformation of a protein kinase,
      without the need to determine costructures by X-ray crystallography. Our results
      suggest broad applicability to other proteins, particularly with single-site
      labels reporting on specific protein movements associated with selectivity.

PMID- 30186744
TI  - Comprehensive analysis of key genes, microRNAs and long non-coding RNAs in
      hepatocellular carcinoma.
AB  - Human hepatocellular carcinoma (HCC) is a common aggressive cancer whose
      molecular mechanism remains elusive. We aimed to identify the key genes,
      microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) involved with HCC. We
      obtained mRNA, miRNA and lncRNA profiles for HCC from The Cancer Genome Atlas and
      then identified differentially expressed mRNAs (DEmRNAs), miRNAs (DEmiRNAs) and
      lncRNAs (DElncRNAs). We performed functional annotation of DEmRNAs and then
      constructed HCC-specific DEmiRNA-DEmRNA, DEmiRNA-DElncRNA and DElncRNA-DEmiRNA
      DEmRNA interaction networks. We searched for nearby target cis-DEmRNAs of
      DElncRNAs and performed receiver operating characteristic and survival analyses.
      A total of 1239 DEmRNAs, 33 DEmiRNAs and 167 DElncRNAs in HCC were obtained.
      Retinol metabolism [false discovery rate (FDR) = 7.02 * 10-14] and metabolism of
      xenobiotics by cytochrome P450 (FDR = 7.30 * 10-11) were two significantly
      enriched pathways in HCC. We obtained 545 DEmiRNA-DEmRNA pairs that consisted of
      258 DEmRNAs and 28 DEmiRNAs in HCC. mir-424, miR-93 and miR-3607 are three hub
      DEmiRNAs of the HCC-specific DEmiRNA-DEmRNA interaction network. HAND2
      AS1/ENSG00000232855-miR-93-LRAT/RND3, ENSG00000232855-miR-877-RCAN1 and
      ENSG00000232855-miR-224-RND3 interactions were found in the HCC-specific DElncRNA
      DEmiRNA-DEmRNA interaction network. A total of three DElncRNA-nearby target
      DEmRNA pairs (HCG25-KIFC1, LOC105378687-CDC20 and LOC101927043-EPCAM) in HCC were
      obtained. Diagnostic and prognostic values of several selected DElncRNAs, DEmRNAs
      and DEmiRNAs for HCC were assessed. Our study identified several DEmRNAs,
      DEmiRNAs and DElncRNAs with great diagnostic or prognostic value for HCC, which
      may facilitate studies into the molecular mechanisms, and development of
      potential biomarkers and therapeutic target sites for HCC.

PMID- 30186745
TI  - Late ribosomal protein localization in Arabidopsis thaliana differs to that in
      Saccharomyces cerevisiae.
AB  - Ribosome biogenesis is essential for cellular function and involves rRNA
      synthesis, rRNA processing and modification, and ribosomal protein assembly.
      Ribosome biogenesis factors and small nucleolar RNA assist these events.
      Ribosomal maturation takes place in the nucleolus, the nucleoplasm, and the
      cytosol in a coordinated and controlled manner. For example, some ribosomal
      proteins are thought to be assembled in the cytoplasm based on the observations
      in Saccharomyces cerevisiae. Here, we used cellular fractionation to demonstrate
      that cleavage of the 20S intermediate, the precursor to mature 18S rRNA, does not
      occur in the nucleoplasm of Arabidopsis thaliana. It most likely occurs in the
      cytoplasm. Further, we verified the proposed localization of RPS10e, RPS26e, and
      RPL24a/b in the nucleus and RPP1 in the nucleolus of A. thaliana by ribosome
      profiling, immunofluorescence, and analysis of the localization of GFP fusion
      proteins. Our results suggest that the order of events during ribosomal protein
      assembly in the ribosome biogenesis pathway differs between plants and yeast.

PMID- 30186746
TI  - Novel ASK1 inhibitor AGI-1067 improves AGE-induced cardiac dysfunction by
      inhibiting MKKs/p38 MAPK and NF-kappaB apoptotic signaling.
AB  - Heart failure has been identified as one of the clinical manifestations of
      diabetic cardiovascular complications. Excessive myocardium apoptosis
      characterizes cardiac dysfunctions, which are correlated with an increased level
      of advanced glycation end products (AGEs). In this study, we investigated the
      participation of reactive oxygen species (ROS) and the involvements of apoptosis
      signal-regulating kinase 1 (ASK1)/mitogen-activated protein kinase (MAPK) kinases
      (MKKs)/p38 MAPK and nuclear factor kappaB (NF-kappaB) pathways in AGE-induced
      apoptosis-mediated cardiac dysfunctions. The antioxidant and therapeutic effects
      of a novel ASK1 inhibitor, AGI-1067, were also studied. Myocardium and isolated
      primary myocytes were exposed to AGEs and treated with AGI-1067. Invasive
      hemodynamic and echocardiographic assessments were used to evaluate the cardiac
      functions. ROS formation was evaluated by dihydroethidium fluorescence staining.
      A terminal deoxynucleotidyl transferase dUTP nick end labelling assay was used to
      detect the apoptotic cells. ASK1 and NADPH activities were determined by kinase
      assays. The association between ASK1 and thioredoxin 1 (Trx1) was assessed by
      immunoprecipitation. Western blotting was used to evaluate the phosphorylation
      and expression levels of proteins. Our results showed that AGE exposure
      significantly activated ASK1/MKKs/p38 MAPK, which led to increased cardiac
      apoptosis and cardiac impairments. AGI-1067 administration inhibited the
      activation of MKKs/p38 MAPK by inhibiting the disassociation of ASK1 and Trx1,
      which suppressed the AGE-induced myocyte apoptosis. Moreover, the NF-kappaB
      activation as well as the ROS generation was inhibited. As a result, cardiac
      functions were improved. Our findings suggested that AGI-1067 recovered AGE
      induced cardiac dysfunction by blocking both ASK1/MKKs/p38 and NF-kappaB
      apoptotic signaling pathways.

PMID- 30186747
TI  - MicroR-9-5p suppresses EV71 replication through targeting NFkappaB of the RIG-I
      mediated innate immune response.
AB  - Accumulating evidence demonstrates that there is a causative link between hsa
      microRNA-9-5p (miR-9) and pathophysiological processes. Enterovirus 71 (EV71) has
      been found to contribute to numerous severe clinical symptoms which result in
      death. The exact mechanism by which EV71 influences miR-9 expression is unknown,
      and the relationship between miR-9 and EV71 is still unclear. Here, miR-9
      expression was found to be impaired upon EV71 infection in several cell lines and
      in an EV71 infection mouse model. Additionally, we confirmed that EV71 infection
      induces robust expression of pro-inflammatory cytokines (TNF-alpha, IL-6, and IL
      1) and interferons (IFN-alpha and IFN-beta). Overexpression of miR-9 attenuated
      EV71 proliferation and reduced protein and gene expressions of virion protein 1
      (VP1) of EV71. Furthermore, we observed that the inflammation caused by EV71
      infection was restored to a moderate level via miR-9 overexpression. Nuclear
      factor kappa B (NFkappaB) in the retinoic acid-induced gene 1 (RIG-I) signaling
      pathway, but not interferon regulating factor 3 (IRF3), was significantly
      decreased and inactivated by ectopic miR-9 expression. Moreover, in mouse
      infection experiments, administration of miR-9 agomirs caused a significant
      decrease in VP1 levels and pro-inflammatory cytokine production after viral
      inoculation. Taken together, the present data demonstrate that miR-9 exerts an
      anti-EV71 effect in cells and a mouse model via mediating NFkappaB activity of
      the RIG-I signal pathway, thereby suggesting a new candidate for antiviral drug
      development.

PMID- 30186748
TI  - Induction of ubiquitin C (UBC) gene transcription is mediated by HSF1: role of
      proteotoxic and oxidative stress.
AB  - The polyubiquitin gene ubiquitin C (UBC) is considered a stress protective gene
      and is upregulated under various stressful conditions, which is probably a
      consequence of an increased demand for ubiquitin in order to remove toxic
      misfolded proteins. We previously identified heat shock elements (HSEs) within
      the UBC promoter, which are responsible for heat shock factor (HSF)1-driven
      induction of the UBC gene and are activated by proteotoxic stress. Here, we
      determined the molecular players driving the UBC gene transcriptional response to
      arsenite treatment, mainly addressing the role of the nuclear factor-erythroid 2
      related factor 2 (Nrf2)-mediated antioxidant pathway. Exposure of HeLa cells to
      arsenite caused a time-dependent increase of UBC mRNA, while cell viability and
      proteasome activity were not affected. Nuclear accumulation of HSF1 and Nrf2
      transcription factors was detected upon both arsenite and MG132 treatment, while
      HSF2 nuclear levels increased in MG132-treated cells. Notably, siRNA-mediated
      knockdown of Nrf2 did not reduce UBC transcription under either basal or
      stressful conditions, but significantly impaired the constitutive and inducible
      expression of well-known antioxidant response element-dependent genes. A
      chromatin immunoprecipitation assay consistently failed to detect Nrf2 binding to
      the UBC promoter sequence. By contrast, depletion of HSF1, but not HSF2,
      significantly compromised stress-induced UBC expression. Critically, HSF1
      mediated UBC trans-activation upon arsenite exposure relies on transcription
      factor binding to previously mapped distal HSEs, as demonstrated to occur under
      proteasome inhibition. These data highlight HSF1 as the pivotal transcription
      factor that translates different stress signals into UBC gene transcriptional
      induction.

PMID- 30186749
TI  - A stable association with PME-1 may be dispensable for PP2A demethylation -
      implications for the detection of PP2A methylation and immunoprecipitation.
AB  - Reversible methyl-esterification (methylation) of Leu309 in the protein
      phosphatase 2A catalytic subunit (PP2Ac) is essential for proper biogenesis of
      the PP2A holoenzyme. Accumulating evidence links PP2Ac methylation to diseases,
      including cancer and neurodegenerative disorders. Protein phosphatase methyl
      esterase (PME-1) specifically catalyzes PP2Ac demethylation. We demonstrate that
      PP2Ac is demethylated in cell extracts even at 0  degrees C unless prevented by a
      PME-1 methyl-esterase inhibitor. This promotes dissociation of PP2A heterotrimers
      with B55 or PR72 subunits, but not those with B56 subunits. These results reveal
      differential sensitivity of ABC heterotrimers to methylation status of the C
      subunit. Our study advocates caution when interpreting earlier findings, offers
      an effective protocol for preserving PP2A complexes, and reveals key distinctions
      between B subunits and their interactions with the AC core dimer of PP2A.

PMID- 30186750
TI  - Death receptor 6 promotes ovarian cancer cell migration through KIF11.
AB  - The expression of death receptor 6 (DR6) is abnormal in some cancer types, but
      the function and underlying molecular mechanisms of DR6 in tumor progression are
      not yet clear. In the present study, our analysis of ovarian cancer RNA
      sequencing data from The Cancer Genome Atlas revealed that DR6 is upregulated in
      human ovarian cancer. We confirmed that the expression level of DR6 is
      upregulated in ovarian cancer tissues when compared with matched adjacent normal
      tissues. In addition, DR6 enhanced ovarian carcinoma cell migration ability, and
      decreased expression of DR6 inhibited the expression of matrix metalloprotease
      (MMP) 2 and MMP9, and increased the expression of E-cadherin. Additionally, DR6
      shRNA caused a significant decrease in phosphoinositide-3-kinase (PI3K), phospho
      (p) -AKT, p-extracellular signal-regulated kinase (ERK), and p-mitogen-activated
      protein kinase kinase expression in SKOV3 cells. These results suggested that DR6
      can enhance ovarian carcinoma cell migration ability through the mitogen
      activated protein kinase/ERK and PI3K/AKT pathways. Notably, mass spectrometric
      analysis indicated that DR6 co-purified with kinesin family member 11 (KIF11),
      and we verified the interaction between KIF11 and DR6 by co-immunoprecipitation
      and glutathione S-transferase pull-down. Furthermore, we demonstrated that DR6
      can bind tumor necrosis factor receptor-associated factor 4 (TRAF4) with co
      immunoprecipitation. Overexpression of KIF11 or TRAF4 eliminated the suppression
      of carcinoma cell migration by DR6 knockdown. We also found that TRAF4 and KIF11
      were upregulated in ovarian carcinomas and that their level of expression was
      positively correlated with that of DR6. The findings above suggest that DR6 may
      play a notable oncogenic role in ovarian malignancy by interacting with TRAF4 and
      KIF11, and that DR6 may be an effective therapeutic target in ovarian cancer.

PMID- 30186751
TI  - MicroRNA-17 as a promising diagnostic biomarker of gastric cancer: An
      investigation combining TCGA, GEO, meta-analysis, and bioinformatics.
AB  - Integrated studies of accumulated data can be performed to obtain more reliable
      information and more feasible measures for investigating potential diagnostic
      biomarkers of gastric cancer (GC) and to explore related molecular mechanisms.
      This study aimed to identify microRNAs involved in GC by integrating data from
      The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus. Through our analysis,
      we identified hsa-miR-17 (miR-17) as a suitable candidate. We performed a meta
      analysis of published studies and analyzed clinical data from TCGA to evaluate
      the clinical significance and diagnostic value of miR-17 in GC. miR-17 was found
      to be upregulated in GC tissues and exhibited a favorable value in diagnosing GC.
      In addition, we predicted that 288 target genes of miR-17 participate in GC
      related pathways. Enrichment of Kyoto Encyclopedia of Genes and Genomes pathway,
      Gene Ontology analysis, and protein-protein interaction analysis of the 288
      target genes of miR-17 were also performed. Through this study, we identified
      possible core pathways and genes that may play an important role in GC. The
      possible core pathways include the cAMP, phosphoinositide-3-kinase-Akt, Rap1, and
      mitogen-activated protein kinase signaling pathways. miR-17 may be involved in
      several biological processes, including DNA template transcription, the
      regulation of transcription from RNA polymerase II promoters, and cell adhesion.
      In addition, cellular components (such as cytoplasm and plasma membrane) and
      molecular functions (such as protein binding and metal ion binding) also seemed
      to be regulated by miR-17.

PMID- 30186752
TI  - 2D DIGE proteomic analysis reveals fasting-induced protein remodeling through
      organ-specific transcription factor(s) in mice.
AB  - Overnight fasting is a routine procedure before surgery in clinical settings.
      Intermittent fasting is the most common diet/fitness trend implemented for weight
      loss and the treatment of lifestyle-related diseases. In either setting, the
      effects not directly related to parameters of interest, either beneficial or
      harmful, are often ignored. We previously demonstrated differential activation of
      cellular adaptive responses in 13 atrophied/nonatrophied organs of fasted mice by
      quantitative PCR analysis of gene expression. Here, we investigated 2-day fasting
      induced protein remodeling in six major mouse organs (liver, kidney, thymus,
      spleen, brain, and testis) using two-dimensional difference gel electrophoresis
      (2D DIGE) proteomics as an alternative means to examine systemic adaptive
      responses. Quantitative analysis of protein expression followed by protein
      identification using matrix-assisted laser desorption ionization-time-of-flight
      mass spectrometry (MALDI-TOFMS) revealed that the expression levels of 72, 26,
      and 14 proteins were significantly up- or downregulated in the highly atrophied
      liver, thymus, and spleen, respectively, and the expression levels of 32 proteins
      were up- or downregulated in the mildly atrophied kidney. Conversely, there were
      no significant protein expression changes in the nonatrophied organs, brain and
      testis. Upstream regulator analysis highlighted transcriptional regulation by
      peroxisome proliferator-activated receptor alpha (PPARalpha) in the liver and
      kidney and by tumor protein/suppressor p53 (TP53) in the thymus, spleen, and
      liver. These results imply of the existence of both common and distinct adaptive
      responses between major mouse organs, which involve transcriptional regulation of
      specific protein expression upon short-term fasting. Our data may be valuable in
      understanding systemic transcriptional regulation upon fasting in experimental
      animals.

PMID- 30186753
TI  - Characterization of genetic alterations in brain metastases from non-small cell
      lung cancer.
AB  - Brain metastasis (BM) is the primary contributor to mortality in non-small cell
      lung cancer (NSCLC) patients. Although the findings of NSCLC genetic sequencing
      studies suggest the potential for personalizing therapeutic approaches, the
      genetic profiles and underlying mechanisms of BM progression remain poorly
      understood. Here, we investigated the genetic profiles of brain metastases from
      NSCLC in six patients with primary tumors and corresponding BM samples via whole
      exome sequencing and targeted panel sequencing. We have demonstrated considerable
      genetic heterogeneity between primary lung cancer and corresponding brain
      metastases specimens. High-frequency mutations were found in
      NOTCH2,NOTCH2NL,FANCD2,EGFR, and TP53. Additionally, EGFR and TP53 consistently
      exhibited high frequencies of mutation between primary tumors and corresponding
      brain metastases. The implication is that most of the genetic alterations may be
      acquired or lost during malignant progression, and the stable EGFR and TP53
      mutational status between paired primary tumors and metastatic sites confirms
      that most mutations detected on analysis of the primary tumor or metastases are
      sufficient for clinical decision-making, and suggest there is no need to re
      biopsy recurrent tumors or metastases for most NSCLC patients.

PMID- 30186755
TI  - Corrigendum to: Contribution of histone N-terminal tails to the structure and
      stability of nucleosomes.
AB  - [This corrects the article DOI: 10.1016/j.fob.2013.08.007.].

PMID- 30186754
TI  - Importance of Val567 on heme environment and substrate recognition of neuronal
      nitric oxide synthase.
AB  - Nitric oxide (NO) produced by mammalian nitric oxide synthases (mNOSs) is an
      important mediator in a variety of physiological functions. Crystal structures of
      mNOSs have shown strong conservation of the active-site residue Val567 (numbering
      for rat neuronal NOS, nNOS). NOS-like proteins have been identified in several
      bacterial pathogens, and these display striking sequence identity to the
      oxygenase domain of mNOS (NOSoxy), with the exception of a Val to Ile mutation at
      the active site. Preliminary studies have highlighted the importance of this Val
      residue in NO-binding, substrate recognition, and oxidation in mNOSs. To further
      elucidate the role of this valine in substrate and substrate analogue
      recognition, we generated five Val567 mutants of the oxygenase domain of the
      neuronal NOS (nNOSoxy) and used UV-visible and EPR spectroscopy to investigate
      the effects of these mutations on the heme distal environment, the stability of
      the heme-FeII-CO complexes, and the binding of a series of substrate analogues.
      Our results are consistent with Val567 playing an important role in preserving
      the integrity of the active site for substrate binding, stability of heme-bound
      gaseous ligands, and potential NO production.

PMID- 30186756
TI  - Combined pulmonary fibrosis and emphysema with myeloperoxidase-antineutrophil
      cytoplasmic antibody positivity that resolved upon smoking cessation.
AB  - Myeloperoxidase antineutrophil cytoplasmic autoantibody (MPO-ANCA) is well-known
      as a serological marker for small-vessel vasculitis. However, when a smoker with
      interstitial lung disease (ILD) exhibits serum ANCA positivity without systemic
      vasculitis, diagnosis is a matter of debate; the relationship between smoking and
      ANCA is unknown. We report a case of combined pulmonary fibrosis and emphysema
      (CPFE) with elevated MPO-ANCA. Surgical lung biopsy showed emphysema and fibrotic
      interstitial pneumonia without vasculitis. The MPO-ANCA level decreased after
      smoking cessation, and no vasculitis or progression was observed during 3 years
      of follow-up. This suggested that smoking cessation was related to normalization
      of MPO-ANCA and corresponding disease activity.

PMID- 30186757
TI  - Pneumocystis Jirovecii (carinii) pneumonia causing lung cystic lesions and
      pneumomediastinum in non-HIV infected patient.
AB  - Pneumomediastinum is a rare, potentially life-threatening complication of PCP
      that occurs in HIV-positive and HIV-negative patients. We are presenting a rare
      case pneumomediastinum caused by pneumocystis Jirovecii pneumonia in a HIV
      negative patient with history of diffuse B-cell lymphoma on R CHOP chemotherapy.
      What is unique about our case is that the patient developed pneumomediastinum
      while in the hospital, on atovaquone that improved when switched to clindamycin
      and primaquine with improvement in her respiratory status. Another interesting
      point is that diagnosis was entertained due to the characteristic CT scan finding
      of ground glass opacities with cystic lung lesions and pneumomediastinum in an
      immunocompromised patient who was started on empirical treatment for PCP. The
      diagnosis was eventually confirmed with PCP PCR.

PMID- 30186758
TI  - Severe metabolic alkalosis-a diagnostic dilemma.
AB  - Background: Cushing's syndrome due to ectopic ACTH secretion has been associated
      with many cancers; most commonly small cell carcinoma of the lung and bronchial
      carcinoid tumors. Usually, patients who confer this diagnosis have poor
      prognosis. Case presentation: A 66-year-old female presented with worsening
      shortness of breath and weakness over three days. Initial laboratory derangements
      included severe hypokalemia and metabolic alkalosis. Treatment included high
      amounts of potassium chloride and acetazolamide. Imaging studies revealed
      anterior medial right upper lobe lung mass as well as suspicion for many liver
      metastases. Liver biopsy was sought and was positive for small cell carcinoma.
      Conclusion: We describe a case of severe metabolic alkalosis and hypokalemia in a
      patient with Cushing's syndrome due to ectopic ACTH secretion from small cell
      lung cancer. To our knowledge, this is the first case identified which exhibited
      such significant metabolic derangements in the form of serum and arterial blood
      bicarbonate. As prognosis is quite poor, we recommend swift diagnosis and
      management.

PMID- 30186759
TI  - Lenalidomide induced durable remission in a patient with MDS/MPN-with ring
      sideroblasts and thrombocytosis with associated 5q- syndrome.
AB  - We describe a patient with MDS/MPN with ring sideroblasts and thrombocytosis who
      had deletions of long arm of chromosome 5 (5q-) and chromosome 20 (20q-).
      Molecular studies showed an exon 9, frame shift mutation in the calreticulin
      (CALR) gene, and absence of mutations in JAK2, MPL, SETBP1 or SF3B1. Treatment
      with lenalidomide resulted in durable clinical remission which has lasted 2
      years.

PMID- 30186760
TI  - Brain functional networks become more connected as amyotrophic lateral sclerosis
      progresses: a source level magnetoencephalographic study.
AB  - This study hypothesizes that the brain shows hyper connectedness as amyotrophic
      lateral sclerosis (ALS) progresses. 54 patients (classified as "early stage" or
      "advanced stage") and 25 controls underwent magnetoencephalography and MRI
      recordings. The activity of the brain areas was reconstructed, and the
      synchronization between them was estimated in the classical frequency bands using
      the phase lag index. Brain topological metrics such as the leaf fraction (number
      of nodes with degree of 1), the degree divergence (a measure of the scale
      freeness) and the degree correlation (a measure of disassortativity) were
      estimated. Betweenness centrality was used to estimate the centrality of the
      brain areas. In all frequency bands, it was evident that, the more advanced the
      disease, the more connected, scale-free and disassortative the brain networks. No
      differences were evident in specific brain areas. Such modified brain topology is
      sub-optimal as compared to controls. Within this framework, our study shows that
      brain networks become more connected according to disease staging in ALS
      patients.

PMID- 30186761
TI  - FDG PET Parkinson's disease-related pattern as a biomarker for clinical trials in
      early stage disease.
AB  - Background: The development of therapeutic interventions for Parkinson disease
      (PD) is challenged by disease complexity and subjectivity of symptom evaluation.
      A Parkinson's Disease Related Pattern (PDRP) of glucose metabolism via
      fluorodeoxyglucose positron emission tomography (FDG-PET) has been reported to
      correlate with motor symptom scores and may aid the detection of disease
      modifying therapeutic effects. Objectives: We sought to independently evaluate
      the potential utility of the PDRP as a biomarker for clinical trials of early
      stage PD. Methods: Two machine learning approaches (Scaled Subprofile Model (SSM)
      and NPAIRS with Canonical Variates Analysis) were performed on FDG-PET scans from
      17 healthy controls (HC) and 23 PD patients. The approaches were compared
      regarding discrimination of HC from PD and relationship to motor symptoms.
      Results: Both classifiers discriminated HC from PD (p < 0.01, p < 0.03), and
      classifier scores for age- and gender- matched HC and PD correlated with Hoehn &
      Yahr stage (R2 = 0.24, p < 0.015) and UPDRS (R2 = 0.23, p < 0.018). Metabolic
      patterns were highly similar, with hypometabolism in parieto-occipital and
      prefrontal regions and hypermetabolism in cerebellum, pons, thalamus, paracentral
      gyrus, and lentiform nucleus relative to whole brain, consistent with the PDRP.
      An additional classifier was developed using only PD subjects, resulting in
      scores that correlated with UPDRS (R2 = 0.25, p < 0.02) and Hoehn & Yahr stage
      (R2 = 0.16, p < 0.06). Conclusions: Two independent analyses performed in a
      cohort of mild PD patients replicated key features of the PDRP, confirming that
      FDG-PET and multivariate classification can provide an objective, sensitive
      biomarker of disease stage with the potential to detect treatment effects on PD
      progression.

PMID- 30186762
TI  - Tractography-assisted deep brain stimulation of the superolateral branch of the
      medial forebrain bundle (slMFB DBS) in major depression.
AB  - Background: Deep brain stimulation (DBS) of the superolateral branch of the
      medial forebrain bundle (slMFB) emerges as a - yet experimental - treatment for
      major depressive disorder (MDD) and other treatment refractory psychiatric
      diseases. First experiences have been reported from two open label pilot trials
      in major depression (MDD) and long-term effectiveness for MDD (50 months) has
      been reported. Objective: To give a detailed description of the surgical
      technique for DBS of the superolateral branch of the medial forebrain bundle
      (slMFB) in MDD. Methods: Surgical experience from bilateral implantation
      procedures in n = 24 patients with MDD is reported. The detailed procedure of
      tractography-assisted targeting together with detailed electrophysiology in 144
      trajectories in the target region (recording and stimulation) is described.
      Achieved electrode positions were evaluated based on postoperative helical CT and
      fused to preoperative high resolution anatomical magnetic resonance imaging (MRI;
      Philips Medical Systems, Best, Netherlands), including the pre-operative
      diffusion tensor imaging (DTI) tractographic information (StealthViz DTI,
      Medtronic, USA; Framelink 5.0, Medtronic, USA). Midcommissural point (MCP)
      coordinates of effective contact (EC) location, together with angles of entry
      into the target region were evaluated. To investigate incidental stimulation of
      surrounding nuclei (subthalamic nucleus, STN; substantia nigra, SNr; and red
      nucleus, RN) as a possible mechanism, a therapeutic triangle (TT) was defined,
      located between these structures (based on MRI criteria in T2) and evaluated with
      respect to EC locations. Results: Bilateral slMFB DBS was performed in all
      patients. We identified an electrophysiological environment (defined by autonomic
      reaction, passive microelectrode recording, acute effects and oculomotor effects)
      that helps to identify the proper target site on the operation table.
      Postoperative MCP-evaluation of effective contacts (EC) shows a significant
      variability with respect to localization. Evaluation of the TT shows that
      responders will typically have their active contacts inside the triangle and that
      surrounding nuclei (STN, SNr, RN) are not directly hit by EC, indicating a
      predominant white matter stimulation. The individual EC position within the
      triangle cannot be predicted and is based on individual slMFB (tractography)
      geometry. There was one intracranial bleeding (FORESEE I study) during a first
      implantation attempt in a patient who later received full bilateral implantation.
      Typical oculomotor side effects are idiosyncratic for the target region and at
      inferior contacts. Conclusion: The detailed surgical procedure of slMFB DBS
      implantation has not been described before. The slMFB emerges as an interesting
      region for the treatment of major depression (and other psychiatric diseases)
      with DBS. So far it has only been successfully researched in open label clinical
      case series and in 15 patients published. Stimulation probably achieves its
      effect through direct white-matter modulation of slMFB fibers. The surgical
      implantation comprises a standardized protocol combining tractographic imaging
      based on DTI, targeting and electrophysiological evaluation of the target region.
      To this end, slMFB DBS surgery is in technical aspects comparable to typical
      movement disorder surgery. In our view, slMFB DBS should only be performed under
      tractographic assistance.

PMID- 30186763
TI  - Callosal and subcortical white matter alterations in schizophrenia: A diffusion
      tensor imaging study at multiple levels.
AB  - Diffusion tensor imaging and its distinct capability to detect micro-structural
      changes in vivo allows the exploration of white matter (WM) abnormalities in
      patients who have been diagnosed with schizophrenia; however, the results
      regarding the anatomical positions and degree of abnormalities are inconsistent.
      In order to obtain more robust and stable findings, we conducted a multi-level
      analysis to investigate WM disruption in a relatively large sample size (142
      schizophrenia patients and 163 healthy subjects). Specifically, we evaluated the
      univariate fractional anisotropy (FA) in voxel level; the bivariate pairwise
      structural connectivity between regions using deterministic tractography as the
      network node defined by the Human Brainnetome Atlas; and the multivariate network
      topological properties, including the network hub, efficiency, small-worldness,
      and strength. Our data demonstrated callosal and subcortical WM alterations in
      patients with schizophrenia. These disruptions were evident in both voxel and
      connectivity levels and further supported by associations between FA values and
      illness duration. Based on the findings regarding topological properties, the
      structural network showed weaker global integration in patients with
      schizophrenia than in healthy subjects, while brain network hubs showed decreased
      functionality. We replicated these findings using an automated anatomical
      labeling atlas to define the network node. Our study indicates that callosal and
      subcortical WM disruptions are biomarkers for chronic schizophrenia.

PMID- 30186764
TI  - Data driven diagnostic classification in Alzheimer's disease based on different
      reference regions for normalization of PiB-PET images and correlation with CSF
      concentrations of Abeta species.
AB  - Positron emission tomography (PET) neuroimaging with the Pittsburgh Compound_B
      (PiB) is widely used to assess amyloid plaque burden. Standard quantification
      approaches normalize PiB-PET by mean cerebellar gray matter uptake. Previous
      studies suggested similar pons and white-matter uptake in Alzheimer's disease
      (AD) and healthy controls (HC), but lack exhaustive comparison of normalization
      across the three regions, with data-driven diagnostic classification. We aimed to
      compare the impact of distinct reference regions in normalization, measured by
      data-driven statistical analysis, and correlation with cerebrospinal fluid (CSF)
      amyloid beta (Abeta) species concentrations. 243 individuals with clinical
      diagnosis of AD, HC, mild cognitive impairment (MCI) and other dementias, from
      the Biomarkers for Alzheimer's/Parkinson's Disease (BIOMARKAPD) initiative were
      included. PiB-PET images and CSF concentrations of Abeta38, Abeta40 and Abeta42
      were submitted to classification using support vector machines. Voxel-wise group
      differences and correlations between normalized PiB-PET images and CSF Abeta
      concentrations were calculated. Normalization by cerebellar gray matter and pons
      yielded identical classification accuracy of AD (accuracy-96%, sensitivity-96%,
      specificity-95%), and significantly higher than Abeta concentrations (best
      accuracy 91%). Normalization by the white-matter showed decreased extent of
      statistically significant multivoxel patterns and was the only method not
      outperforming CSF biomarkers, suggesting statistical inferiority. Abeta38 and
      Abeta40 correlated negatively with PiB-PET images normalized by the white-matter,
      corroborating previous observations of correlations with non-AD-specific
      subcortical changes in white-matter. In general, when using the pons as reference
      region, higher voxel-wise group differences and stronger correlation with
      Abeta42, the Abeta42/Abeta40 or Abeta42/Abeta38 ratios were found compared to
      normalization based on cerebellar gray matter.

PMID- 30186766
TI  - Herpes simplex laryngitis presenting as airway obstruction in a stroke patient.
AB  - We present the second confirmed report of HSV laryngitis in an adult stroke
      patient, resulting in complicated airway management issues. This rare
      presentation of laryngeal HSV in a stroke patient can interfere with speech,
      language, and swallowing functions and confounds the etiology of these issues,
      which can impact subsequent management.

PMID- 30186765
TI  - Relating resting-state hemodynamic changes to the variable language profiles in
      post-stroke aphasia.
AB  - Linking both structural lesions and the functional integrity of remaining brain
      tissue to patients' behavioural profile may be critical in discovering the limits
      of behavioural recovery post stroke. In the present study, we explored the
      relationship between temporal hemodynamic changes and language performance in
      chronic post-stroke aphasia. We collected detailed language and
      neuropsychological data for 66 patients with chronic (>1 year) post-stroke
      aphasia. We used principal component analysis to extract their core language
      neuropsychological features. From resting-state fMRI scans in 35 patients, we
      calculated the lag in the time-course of the intact brain voxels in each patient.
      Finally, variation across the language-cognitive factors was related to both the
      patients' structural damage and the time-course changes in each patient's intact
      tissue. Phonological abilities were correlated with the structural integrity of
      the left superior temporal, angular gyrus, supramarginal gyrus and arcuate
      fasciculus regions and hemodynamic advance in the left intra-parietal sulcus.
      Speech fluency related to integrity of premotor regions, plus hemodynamic advance
      in the left middle/superior temporal gyrus, left middle occipital gyrus, and
      right angular gyrus. Semantic performance reflected a combination of medial
      ventral temporal lobe status and hemodynamic delay in the left posterior middle
      temporal gyrus. Finally, executive abilities correlated with hemodynamic delay in
      the left middle/inferior frontal gyrus, right rolandic operculum, bilateral
      supplementary motor areas/middle cingulum areas, and bilateral thalamus/caudate.
      Following stroke, patients' patterns of chronic language abilities reflects a
      combination of structural and functional integrity across a distributed network
      of brain regions. The correlation between hemodynamic changes and behaviours may
      have clinical importance.

PMID- 30186767
TI  - Recurrent bilateral penile fracture: Case report.

PMID- 30186769
TI  - BRCA1 and BRCA2 Mutations Other Than the Founder Alleles Among Ashkenazi Jewish
      in the Population of Argentina.
AB  - In Ashkenazi Jewish (AJ) high risk families 3 mutations [2 in BRCA1 (c. 68_69del
      and c.5266dup) and 1 in BRCA2 (c.5946del)] account for the majority of high risk
      breast and ovarian cancer cases in that ethnic group. Few studies with limited
      number of genotyped individuals have expanded the spectrum of mutations in both
      BRCA genes beyond the 3 mutation panel. In this study, 279 high risk individual
      AJ were counseled at CEMIC (Centro de Educacion Medica e Investigaciones
      Clinicas), and were genotyped first for the 3 recurrent mutation panel followed
      by Next Generation Sequencing (NGS) of BRCA1 BRCA2 in 76 individuals who tested
      negative for the first genotyping step. Of 279 probands (259 women), 55 (50
      women) harbored one of the 3 mutations (19.7%); Of 76 fully sequenced cases (73
      women), 6 (5 women) (7.9%) carried a pathogenic mutation: in BRCA1, c.2728C>T -
      p.(Gln910*); c.5407-?_(*1_?)del and c.5445G>A - p.(Trp1815*); in BRCA2, c.5351dup
      - p.(Asn1784Lysfs*3); c.7308del - p.(Asn2436Lysfs*33) and c.9026_9030del -
      p.(Tyr3009Serfs*7). Of 61 mutation carriers the distribution was as follows: 11
      cancer free at the time of genotyping, 34 female breast cancer cases with age
      range 28-72 years (41.6 +/- 9.3), 3 male breast cancer cases with age range 59-75
      years (65 +/- 7.3), 6 breast and ovarian cancer cases with age range 35-60 years
      (breast 40.4 +/- 5.2; ovary 47.8 +/- 7.2) and 7 ovarian cancer cases with age
      range 41-77 years (60.6 +/- 13.3). This information proved highly useful for
      counseling, treatment, and prevention for the patient and the family. In
      conclusion comprehensive BRCA1/2 testing in AJ high risk breast ovarian cancer
      cases adds valuable clinically relevant information in a subset of cases
      estimated up to 7% and is therefore recommended.

PMID- 30186770
TI  - Incidence of Pathogenic Variants in Those With a Family History of Pancreatic
      Cancer.
AB  - Discovery of a hereditary cancer syndrome can be one of the factors that
      determine whether a healthy individual completes pancreas cancer screening or
      whether an individual with cancer receives certain chemotherapies. Retrospective
      review was completed to determine the likelihood of detection of a pathogenic
      variant causing a hereditary cancer syndrome based on personal and family
      history. Study was completed through the hereditary cancer clinic at Mayo Clinic
      Florida over a 6 year period, 1/2012 through 1/2018. All participants were
      referred based on suspicion for a hereditary cancer syndrome based on personal
      and/or family history. Patients' personal oncologic history at time of
      consultation was recorded, as well as, cancer diagnoses in the family history and
      the number of family members with a history of pancreas cancer. Test result and
      gene name, if variant was pathogenic or likely pathogenic, were noted as well. A
      total of 2,019 patients completed genetic testing during study period. Personal
      history of cancer included a variety of primaries, including breast (N = 986),
      ovarian (N = 119), colon (N = 106), prostate (N = 65), and pancreas (N = 59). A
      positive result was discovered in 11% of the total group. Two hundred and eighty
      five reported a family history of pancreas cancer. The incidence of pathogenic
      variants was 13% (37/285) in those with any family history and 23% (13/56) in
      those with two or more relatives with pancreatic cancer. Those with multiple
      relatives with pancreatic cancer were significantly more likely to carry a
      pathogenic variant than those with a personal history of breast cancer under the
      age of 45 (23.2 vs. 11.9%, p = 0.02). Presence of multiple family members with a
      reported history of pancreatic cancer significantly increased the likelihood that
      a pathogenic variant would be identified in the patient even over other
      significant risk factors, like personal history of early onset breast cancer.

PMID- 30186768
TI  - Plasticity of Type I Interferon-Mediated Responses in Cancer Therapy: From Anti
      tumor Immunity to Resistance.
AB  - The efficacy of several therapeutic strategies against cancer, including
      cytotoxic drugs, radiotherapy, targeted immunotherapies and oncolytic viruses,
      depend on intact type I interferon (IFN) signaling for the promotion of both
      direct (tumor cell inhibition) and indirect (anti-tumor immune responses)
      effects. Malfunctions of this pathway in tumor cells or in immune cells may be
      responsible for the lack of response or resistance. Although type I IFN signaling
      is required to trigger anti-tumor immunity, emerging evidence indicates that
      chronic activation of type I IFN pathway may be involved in mediating resistance
      to different cancer treatments. The plastic and dynamic features of type I IFN
      responses should be carefully considered to fully exploit the therapeutic
      potential of strategies targeting IFN signaling. Here, we review available
      evidence supporting the involvement of type I IFN signaling in mediating
      resistance to various cancer therapies and highlight the most promising
      modalities that are being tested to overcome resistance.

PMID- 30186771
TI  - Dengue Virus Infects Primary Human Hair Follicle Dermal Papilla Cells.
AB  - During the epidemic of the dengue virus (DENV) infection in Taiwan in 2014 and
      2015, we observed an abnormally high frequency of increased scalp hair shedding
      in infected individuals that could not be explained by telogen effluvium. In this
      study, the mechanism of hair loss caused by DENV was explored. Human hair
      follicle dermal papilla cells (HFDPCs) are essential for hair follicle
      morphogenesis and cycling. Thus, we established an in vitro DENV infection model
      in HFDPCs. On immunofluorescence analysis, HFDPCs that were susceptible to DENV
      infection responded to type I interferon (IFN) treatment, and the cells showed
      antibody-dependent enhancement (ADE) effect. The expression of the pro
      inflammatory cytokines, interleukin 6 (IL-6), and tumor necrosis factor-alpha
      (TNF-alpha), revealed an inflammatory response in DENV-infected HFDPCs. In
      particular, DENV infection impaired cell viability, and it activated caspase
      associated cell death signaling in HFDPCs. In conclusion, our data indicate that
      direct infection with DENV causes inflammation and cell death in HFDPCs, which is
      involved in the mechanisms of hair loss after DENV infection. The knowledge of
      DENV infection in an immune-privileged tissue, such as hair follicles, may
      suggest their use for further studies on post-dengue fatigue syndrome (PDFS).

PMID- 30186773
TI  - The Key Role of c-Fos for Immune Regulation and Bacterial Dissemination in
      Brucella Infected Macrophage.
AB  - The cellular oncogene c-Fos (c-Fos) is a component of activator protein 1 (AP1),
      a master transcriptional regulator of cells. The suppression of c-Fos signaling
      by siRNA treatment resulted in significant induction of TLR4, which subsequently
      activates p38 and ERK1/2 mitogen-activated protein kinases (MAPKs) and enhances F
      actin polymerization, leading to an increase in B. abortus phagocytosis. During
      B. abortus infection, c-Fos signaling is induced, which activates the downstream
      innate-immunity signaling cascade for bacterial clearance. The inhibition of c
      Fos signaling led to increased production of interleukin 10 (IL-10), which
      partially suppressed lysosome-mediated killing, resulting in increased survival
      of B. abortus inside macrophages. We present evidence of the regulatory role
      played by the c-Fos pathway in proliferation during B. abortus infection;
      however, this was independent of the anti-Brucella effect of this pathway.
      Another finding is the essential contribution of c-Fos/TRAIL to infected-cell
      necrosis, which is a key event in bacterial dissemination. These data provide the
      mechanism via which c-Fos participates in host defense mechanisms against
      Brucella infection and in bacterial dissemination by macrophages.

PMID- 30186772
TI  - Staphylococcus aureus Extracellular Vesicles Elicit an Immunostimulatory Response
      in vivo on the Murine Mammary Gland.
AB  - Staphylococcus aureus is a major pathogen responsible for bovine mastitis, the
      most common and costly disease affecting dairy cattle. S. aureus naturally
      releases extracellular vesicles (EVs) during its growth. EVs play an important
      role in the bacteria-bacteria and bacteria-host interactions and are notably
      considered as nanocarriers that deliver virulence factors to the host tissues.
      Whether EVs play a role in a mastitis context is still unknown. In this work, we
      showed that S. aureus Newbould 305 (N305), a bovine mastitis isolate, has the
      ability to generate EVs in vitro with a designated protein content. Purified S.
      aureus N305-secreted EVs were not cytotoxic when tested in vitro on MAC-T and PS,
      two bovine mammary epithelial cell lines. However, they induced the gene
      expression of inflammatory cytokines at levels similar to those induced by live
      S. aureus N305. The in vivo immune response to purified S. aureus N305-secreted
      EVs was tested in a mouse model for bovine mastitis and their immunogenic effect
      was compared to that of live S. aureus N305, heat-killed S. aureus N305 and to S.
      aureus lipoteichoic acid (LTA). Clinical and histopathological signs were
      evaluated and pro-inflammatory and chemotactic cytokine levels were measured in
      the mammary gland 24 h post-inoculation. Live S. aureus induced a significantly
      stronger inflammatory response than that of any other condition tested.
      Nevertheless, S. aureus N305-secreted EVs induced a dose-dependent neutrophil
      recruitment and the production of a selected set of pro-inflammatory mediators as
      well as chemokines. This immune response elicited by intramammary S. aureus N305
      secreted EVs was comparable to that of heat-killed S. aureus N305 and, partly, by
      LTA. These results demonstrated that S. aureus N305-secreted EVs induce a mild
      inflammatory response distinct from the live pathogen after intramammary
      injection. Overall, our combined in vitro and in vivo data suggest that EVs are
      worth to be investigated to better understand the S. aureus pathogenesis and are
      relevant tools to develop strategies against bovine S. aureus mastitis.

PMID- 30186774
TI  - IFN-gamma Response Is Associated to Time Exposure Among Asymptomatic Immune
      Responders That Visited American Tegumentary Leishmaniasis Endemic Areas in Peru.
AB  - Clinical manifestations of American Tegumentary Leishmaniasis (ATL) include
      cutaneous (CL) and mucous forms (ML); however, there are asymptomatic individuals
      who despite being infected do not present any clinical manifestations. This study
      characterized the cell-mediated immunity of travelers who lived in the Andean
      highlands of Cusco, free of leishmaniasis transmission, which eventually visited
      leishmaniasis endemic in the Amazonian basin and returned home without any
      clinical signs of the disease. Their immune response was compared with CL and ML
      patients who acquired the disease during their stage in the same region. Fifty
      four human subjects from the highlands of Cusco (Peru), who have visited an
      endemic area, were enrolled: 28 of them did not show any symptoms, 12 showed CL
      and 14 showed ML. Ten healthy subjects from a non-endemic area (HS) were included
      as controls. T-cell proliferation was evaluated using peripheral blood
      mononuclear cells (PBMC) stimulated for 5 days with a total soluble leishmanial
      antigen (TSLA) of L. (V.) braziliensis. Th1/Th2/Th17 cytokines were also
      quantified in the supernatants by a flow cytometry multiplex assay. T-cell
      proliferation was expressed as stimulation index (SI) and the cut off was fixed
      at SI >2.47. Fifteen out of 28 subjects did not show any signs of disease (54%);
      subjects with an SI above the cut off. They were defined as asymptomatic immune
      responders (AIR). CL and ML patients presented a higher SI than HS and AIR. Among
      the latter group, the exposure time to Leishmania was clearly associated with the
      IFN-gamma response. Increased levels of this cytokine were observed in
      individuals who remained <90 days in an endemic area of leishmaniasis. Our
      results evidenced two sub-populations among asymptomatic individuals, one AIR who
      did not develop clinical disease manifestations when they were exposed to
      Leishmania in endemic areas. Exposure time to Leishmania in the wild was
      associated with the IFN-gamma response.

PMID- 30186775
TI  - Attenuation of Listeria monocytogenes Virulence by Cannabis sativa L. Essential
      Oil.
AB  - Anti-virulence strategies are being explored as a novel approach to combat
      pathogens. Such strategies include inhibition of surface adhesion, tissue
      invasion, toxin production, and/or interference with the gene regulation of other
      virulence traits. Listeria monocytogenes, the causative agent of listeriosis, is
      a facultative intracellular food pathogen characterized by a wide distribution in
      the environment. Its ability to persist within biofilms and to develop resistance
      to sanitizers is the cause of significant problems in food processing plants and
      of steep costs for the food industry. In humans, the treatment of listeriosis is
      hampered by the intracellular location of listeriae and the poor intracellular
      penetration of some antibiotics. Eleven L. monocytogenes isolates from patients
      who were diagnosed with invasive listeriosis in Italy in 2014-2016 were studied.
      This in vitro and in vivo study explored the antibacterial and anti-virulence
      properties of a steam-distilled essential oil of Cannabis sativa L., which is
      being intensively investigated for its high content in powerful bioactive
      phytochemicals. Susceptibility experiments demonstrated a moderate bactericidal
      activity of the essential oil (Minimum Bactericidal Concentration > 2048 MUg/mL).
      Assessment of the effects of sublethal concentrations of the essential oil on L.
      monocytogenes virulence traits demonstrated a significant action on motility.
      Listeriae were non-motile after exposure to the essential oil. Light and scanning
      electron microscopy documented aggregates of listeriae with the flagella trapped
      inside the cluster. Real-time RT-PCR experiments showed downregulation of
      flagellar motility genes and of the regulatory gene prfA. The ability to form
      biofilm and to invade Caco-2 cells was also significantly reduced. Galleria
      mellonella larvae infected with L. monocytogenes grown in presence of sublethal
      concentrations of the essential oil showed much higher survival rates compared
      with controls, suggesting that the extract inhibited tissue invasion. Food
      contamination with L. monocytogenes is a major concern for the food industry,
      particularly for plants making ready-to-eat and processed food. The present work
      provides a baseline in the study of the anti-virulence properties of the C.
      sativa essential oil against L. monocytogenes. Further studies are needed to
      understand if it could be used as an alternative agent for the control of L.
      monocytogenes in food processing plants.

PMID- 30186778
TI  - Policies to Promote Medical Tourism in Korea: A Narrative Review.
AB  - Background: There is a growing global demand for medical tourism while more
      people are moving across borders in Asia, offering new opportunities to the high
      value medical tourism market. The purpose of this study was to provide grounds
      for promoting the International Meditour Coordinator (IMC), issued as a national
      license in Korea and to provide the evidence for the efficient use of the IMC in
      the field of health care. Methods: We examined the trend of professional manpower
      in the rapidly-changing Korean medical market by analyzing the operational status
      of professional manpower in order to promote medical tourism, which began in 2009
      in Korea. We also analyzed the problems of the national qualification system for
      the IMC and sought to improve the professionalism and usability of the national
      qualification system by improving the quality satisfaction of the professionals
      who support the growth of the medical tourism industry. Results: In Korea, IMCs
      are responsible for detailed support services in clinics, support to tourists,
      medical tourism marketing to support the advancement of domestic and
      international medical institutions in each market, medical tourism counseling,
      risk management, and administrative work, thereby contributing to the development
      and enhancement of competitiveness in Korea's global healthcare industry.
      Conclusion: To support the growth of the medical tourism industry, which is a
      global trend, and increase user satisfaction with the quality of medical tourist
      services, it is urgently necessary to establish human resource management policy
      guidelines in the medical tourism industry based on the current operational
      status of professional human resources and the future prospect of supply and
      demand in the sector.

PMID- 30186777
TI  - Circadian Rhythm, Lifestyle and Health: A Narrative Review.
AB  - Background: The circadian rhythm regulation plays a crucial role in people's
      healthy lives affected by factors consisting of cosmic events related to the
      universe and earth, environmental factors (light, night and day duration,
      seasons) and lifestyles. These factors changes lead to disturbance of circadian
      rhythm and it causes increasing the incidence of mental diseases like depression
      and physiological problems like cancers, cardiovascular disease and diabetes.
      Methods: The present review searched Elsevier, SID, Pub Med, Springer, and Google
      Scholar databases for relevant articles were published between 1996 and 2017.
      Keywords used included lifestyle, circadian rhythm, cancer, metabolic diseases
      and cosmic factors. Results: Circadian rhythm can be affected by lifestyle,
      heredity, cosmos spin and seasonal factors. Two first factors have physically
      direct effects on circadian rhythm and health, while other factors influence on
      them mentally. After all, all of them lead to cancer, cardiovascular diseases and
      metabolic obesity. Conclusion: Although environmental factors are universal
      events which are unrelated to human control but affect human's body and circadian
      rhythm. Other factors are manageable by human to prevent disturbance of circadian
      rhythm making physical disorders.

PMID- 30186776
TI  - Application of Bacteriophages in the Agro-Food Sector: A Long Way Toward
      Approval.

PMID- 30186779
TI  - Emotional Labor in the Care Field and Empathy-enhancing Education by Reading
      Literature: A Brief Review.
AB  - Background: Nursing is not just task-based work, but also emotional work. Nurses
      are also obliged to satisfy patients' emotional needs, which often results in
      burnout and depression. We aimed to propose an effective method for reducing
      their emotional burden. Methods: We took theoretical measure to verify some
      theories on emotion and emotional labor. Results: Empathy can be enhanced by
      reading literature. It has been recognized from ancient times that reading is an
      empathic experience in its very essence. Reading is not possible without the
      reader identifying and sympathizing with the character in the story. Conclusion:
      Reading literature is not only an efficient means of enhancing empathy, but also
      very practical to implement. Among programs that proved efficient are role
      exchange programs, here-and-now spontaneity, perspective taking, simulation
      exercises, and so on. The problem with them is that they require special
      facilities and equipment. If they are not available, reading practice would be
      the best alternative.

PMID- 30186780
TI  - Effects of Different Treatment Methods on the Clinical and Urodynamic State of
      Perimenopausal Women with Stress Urinary Incontinence.
AB  - Background: This study was designed to investigate the clinical effects of
      different treatment methods on stress urinary incontinence (SUI) in
      perimenopausal women, and to evaluate urodynamic characteristics. Methods:
      Seventy-two menopausal female patients with stress urinary incontinence were
      included in the Second Affiliated Hospital of Soochow University from January
      2016 to July 2017. The cases were divided into 3 groups of 24 each, depending on
      the treatment received. Group A patients received treatment with electrical
      stimulation combined with biofeedback; those in group B received conventional
      pelvic floor muscle exercise therapy; and those in group C did not have any
      treatment. Relevant clinical parameters of urination were determined including
      pelvic floor muscle strengths, urine dynamics indexes and ICS quality of life
      survey scores; results were averaged in each group for comparisons among the
      three groups before and after the 60-day study period. Results: After treatment
      for 60 days, both group A and B patients displayed a clear improvement in their
      urinary incontinence, pelvic floor muscle strength, leakage times, frequency of
      urination, urine dynamics index and ICS scores (P<0.05), with group A showing the
      most improvement. Women in group C showed no significant difference before and
      after the 60-day study period (P>0.05). Conclusion: Both the method of electrical
      stimulation combined with biofeedback, and conventional pelvic floor muscle
      exercises could help perimenopausal women with stress urinary incontinence;
      however, electrical stimulation combined with biological feedback seems to bring
      about better clinical effects.

PMID- 30186781
TI  - Nutrient Intakes Status and Physical Inactivity among Overweight and Obese School
      Children in Kota Bharu, Kelantan, Malaysia.
AB  - Background: The study examined the baseline findings of a controlled intervention
      study comprising anthropometric measurements, nutrient intakes, and physical
      activity among overweight or obese children in Kota Bharu, Kelantan, Malaysia.
      Methods: The study was completed in 2016 and the baseline data were gathered from
      four groups in a school-based randomized community trial among Year Five students
      from primary schools in Kota Bharu, Kelantan, Malaysia. Participants completed
      anthropometry assessment, three-day dietary record, and Physical Activity
      Questionnaire for Older Children (PAQ-C). Results: The prevalence of obesity was
      higher among the boys (52.5%). Mean energy intake was significantly higher among
      boys as compared to the girls (P=0.003). Twenty-five percent of the participants
      had exceeded the recommended nutrient intakes (RNI) of energy recommended. The
      calcium, thiamine, riboflavin, and niacin were also significantly higher among
      boys as compared to the girls (P<0.05). Boys also exhibited a significantly
      higher score on performance of physical activity (mean=2.68; SD=0.60) as compared
      to the girls (mean=2.38; SD=0.51) however it is still in the category of
      moderately active. Approximately 14.4% of children had a very low physical
      activity level. Conclusion: Overweight and obese boys had higher energy and fat
      intakes but were more physically active as compared to the girls. These findings
      might be useful in planning appropriate intervention strategies to be designed
      and delivered especially for this cohort.

PMID- 30186782
TI  - Influential Factors of Residents' Health in Regions of China: A Comparative
      Study.
AB  - Background: With the rapid growth of China's economy, the country's economic,
      social, and environmental development has also shown significant differences in
      various regions. Improving the health level of residents has gradually become a
      hot issue. We aimed to explore the difference of the health level of the
      residents in different regions of China and its influential factors. Methods: A
      panel regression model was established using statistical data from 31 provinces
      in the eastern, central, and western regions of China from the years 2000 and
      2016 to examine the influence of economic, environmental, and social factors on
      the health level of residents in these regions and investigate the regulating
      role of public service factors. Results: Environmental pollution significantly
      promotes human mortality in the eastern and central regions of China. The
      urbanization rate significantly reduces human mortality in the eastern and
      central regions. Per capita gross domestic product in the eastern and western
      regions has a significant U-shaped relationship with human mortality. The number
      of beds in health institutions per 10,000 persons, average years of schooling,
      and endowment insurance contribution service have varying degrees of influence on
      residents' health level in the three regions of China. In particular, endowment
      insurance contribution service significantly reduces human mortality in the
      eastern region, whereas its impact on the western region is insignificant.
      Conclusion: Differential policies in environmental pollution control, economic
      growth, and medical and public health should be formulated to reduce mortality in
      China, specifically in the eastern, central, and western regions.

PMID- 30186783
TI  - Biochemical Profile of an Adult Diabetic Population from Algeria in Relation with
      Anthropometric Parameters, Age and Gender.
AB  - Background: Diabetes is now a real global disease in particular due to various
      health problems associated with it. This study aimed to establish the
      relationship between diabetes and some biochemical parameters to assess the
      metabolic profile of an adult diabetic population in the region of Tebessa
      (Northeast Algeria). Methods: A cross-sectional survey was conducted at the
      Public Health Facility and the House of Diabetics in Tebessa between Feb 2013 and
      Apr 2013. The study included 200 subjects (100 controls and 100 diabetics) aged
      18-85 yr, chosen completely randomly. Results: Type 2 diabetes mellitus (37%) was
      significantly more frequent than type 1 diabetes mellitus (13%). It was
      significantly more frequent in women than in men. The diabetes was highly
      correlated with the age and body mass index of patients. Moreover, the two types
      of diabetics have significantly more diseases and metabolic disorders compared to
      control subjects. Conclusion: Diabetics especially type 2 has significantly
      higher metabolic disorders and associated diseases than type 1 and control
      subjects.

PMID- 30186784
TI  - Four Non-functional FUT1 Alleles Were Identified in Seven Chinese Individuals
      with Para-Bombay Phenotypes.
AB  - Background: The para-Bombay phenotype is characterized by a lack of ABH antigens
      on red cells, but ABH substances are found in saliva. Molecular genetic analysis
      was performed for seven Chinese individuals serologically typed as para-Bombay in
      Blood Station Center of Ningbo, Zhejiang Province, Ningbo, China from 2011 to
      2014. Methods: RBCs' phenotype was characterized by standard serologic technique.
      Genomic DNA was sequenced with primers that amplified the coding sequence of
      alpha (1, 2)-fucosyltransferase genes FUT1 (or H) and FUT2 (or Se), respectively.
      Routine ABO genotyping analysis was performed. Haplotypes of FUT1 were identified
      by TOPO cloning sequencing. Phylogenetic tree of H proteins of different
      organisms was performed using Mega 6 software. Results: Seven independent
      individuals were demonstrated to possess the para-Bombay phenotype. RBC ABO
      genotypes correlated with ABH substances in their saliva. FUT1 547delAG (h1),
      FUT1 880delTT (h2), FUT1 658T (h3) and FUT1 896C were identified in this study.
      FUT1 896C was first revealed by our team. The H-deficient allele reported here
      was rare and the molecular basis for H deficient alleles was diverse as well in
      the Chinese population. In addition, the FUT2 was also analyzed, only one FUT2
      allele was detected in our study: Se357. Phylogenetic tree of the H proteins
      showed that H proteins could work as an evolutionary and genetic marker to
      differentiate organisms in the world. Conclusion: Molecular genetic backgrounds
      of seven Chinese individuals were summarized sporadic and random mutations in the
      FUT1 gene are responsible for the inactivation of the FUT1-encoded enzyme
      activity.

PMID- 30186785
TI  - Assessment of Ambient Air Pollution in Istanbul during 2003-2013.
AB  - Background: We investigated the air quality changes from 2003-2013 in Istanbul,
      Turkey. Methods: We studied SO2, CO and PM concentration patterns in 10 districts
      of Istanbul. The data was obtained from air pollution monitoring stations of
      Istanbul Metropolitan Municipality Environmental Protection Department. We
      compared the variations of mean concentrations monthly, yearly and seasonally.
      The winter season was accepted from Oct to Mar and the summer season from Apr to
      Sep. Results: The highest monthly average values for all measurements of sulfur
      dioxide and CO were 12.61, 949.19 MUg/m3 in Sarachane respectively. The Highest
      value of the monthly average of the Particulate Matter was 72.07 MUg/m3 in Kartal
      district. During the period between 2003-2013, monthly mean concentration values
      of different districts differed significantly in levels of SO2 (P=0.012), CO
      (P=0.029), and PM (P=0.024). Conclusion: The emissions of air pollutants (SO2,
      PM, and CO) decreased considerably from 2003 to 2013.

PMID- 30186786
TI  - Prevalence of Vitamin D Deficiency during Second Trimester of Pregnancy in
      Shanghai China, Risk Factors and Effects on Pregnancy Outcomes.
AB  - Background: Vitamin D plays important roles in various physiological processes.
      Vitamin D deficiency is common among pregnant women in some regions, such as
      China. Our study aimed to determine the prevalence of Vitamin D deficiency during
      second trimester of pregnancy in Shanghai China, and explore its risk factors and
      effects on pregnant outcomes. Methods: Overall, 23100 pregnant women (2013 to
      2017, Shanghai, China) were included and vitamin D concentrations were measured
      at 16 weeks of gestation. Correlations between vitamin D concentrations and
      participants' general data and maternal and infant outcomes were analyzed by chi
      square test. Non-conditional multivariate logistic regression analysis was used
      to screen the independent risk factors for vitamin D deficiency. Results: Vitamin
      D deficiency was significantly correlated with aging, education level, smoking,
      dirking, BMI before pregnancy, body weight gain during pregnancy (P<0.01), the
      use of vitamin D supplement and milk consumption, and older than 30 years,
      drinking, smoking, BMI before pregnancy> 36, body weight gain during pregnancy<
      40g per day, no daily milk consumption, no vitamin D supplement, and education
      lever below college were independent risk factors for vitamin D deficiency in
      second trimester of pregnancy. In addition, vitamin D deficiency in second
      trimester of pregnancy was closely correlated with the occurrence of a serious of
      adverse maternal and infant outcomes. Conclusion: Vitamin D deficiency was still
      common among women in second trimester of pregnancy in Shanghai China. Vitamin D
      deficiency was closely correlated with the occurrence of a serious of adverse
      maternal and infant outcomes.

PMID- 30186787
TI  - Investigation of Physicho-chemical Properties and Characterization of Produced
      Biosurfactant by Selected Indigenous Oil-degrading Bacterium.
AB  - Background: Due to the amphipathic properties of biosurfactants which act on
      surfaces and interfaces interest by a variety of industries such as cosmetic,
      pharmaceutical, bioremediation and petroleum-related industries has recently
      increased. Methods: Detection of a high-efficiency biosurfactant producer using
      preliminary screening methods from soil contaminated with crude oil was carried
      at the Microbiology Laboratory at Shahid Beheshti University, Tehran, Iran in
      2013. Then after characterization of some physico-chemical properties of produced
      biosurfactant and production optimization conditions, processes of purification
      and complete identification were done. Results: Pseudomonas aeruginosa sp. ZN was
      selected as high-efficiency biosurfactant producing strain from soil contaminated
      with oil from Ahvaz City, Khuzestan Province, southern Iran. The biosurfactant
      production in modified BH2 culture medium supplemented with 1% n-hexadecane
      occurred during exponential phase resulting in a reduction surface tension from
      70 to 29 mN/m. Strain ZN produced biosurfactant with different properties to
      other Pseudomonas reported. These characterizations included continued production
      at C/N ratio range of 10-40; the produced biosurfactant could not separate stable
      emulsion of span-80-kerosene: Tween-80-distilled water (30:70) within 24 h. The
      produced biosurfactants were able to increase hydrophobicity of bacterial cell to
      55%. Recovery of biosurfactants from cell-free supernatant was performed with
      acid precipitation and ammonium sulfate precipitation. Chemical analysis such as
      spraying techniques on developed TLC plate and staining methods of supernatant
      indicated that produced biosurfactants were glycolipids, characterized by ESI-MS
      analysis of extracted product as di-rhamnolipids. Conclusion: Ability of this
      strain to produce biosurfactant in the presence of cooked oil and n-hexadecane
      make it an optimistic candidate for biodegradation of some derivatives of crude
      oil and food industry.

PMID- 30186788
TI  - Exploration and Consideration of the Medical Alliance Modes.
AB  - Background: The distribution of medical resources in China has long been in an
      unbalanced state. Since 2009, the government has initiated the planning and
      construction of a sound grass-roots medical and health service system, increased
      investment in grass-roots medical and health institutions, but it has not
      received the expected results. In order to solve the problem, the medical
      consortium-with a full-featured, hierarchical and resource-sharing structure has
      been proposed. Methods: Overall, 1000 Electronic questionnaires about cognitive
      status of residents on medical alliance were randomly distributed in 50 community
      health service centers in 10 cities including Xuzhou, Nanjing, Hefei, Jinan,
      Zhengzhou, Changsha, Wuhan, Xi'an, Nanchang and Chengdu, China. Results: 94.84%
      of the respondents responded they had heard about the construction of medical
      alliance, but they did not know the specific content. When asked about the
      preferred medical institution after illness, 93.50% participants preferred third
      tier general hospital or specialist hospital. 62.58% of the respondents believe
      that the establishment of the medical alliance has not yet played a role and they
      are concerned that it cannot be effectively implemented. 62.27% of respondents
      were attracted by the convenience of medical alliance, 20.72% of respondents
      thought that they could easily get to famous doctors when they were in need, and
      5.46% of respondents thought that there was no advantage in medical alliance.
      Conclusion: The establishment of the medical alliance is an effective means to
      promote the optimal allocation of medical and health resources. Government should
      perform its functions, and medical institutions and the whole society should all
      participate.

PMID- 30186790
TI  - Human Health Risk Assessment of Cd, Cu, Pb and Zn through Consumption of Raw and
      Pasteurized Cow's Milk.
AB  - Background: The analysis of the residual contents of heavy and toxic metals in
      foodstuff especially milk could be an important indicator of safety, quality, and
      level of pollution of the region in which the milk was produced. Therefore, the
      present investigation was carried out to assess human health risk of residues
      levels of four metals (Cd, Cu, Pb, and Zn) through consumption of raw and
      pasteurized cow's milk. Methods: In this analytical-observational study, totally
      72 samples of raw and pasteurized cow's milk samples were collected from market
      basket of Hamadan City, western Iran in 2014. After preparation and processing
      the samples in the laboratory, the concentration of metals were determined using
      inductively coupled plasma (ICP-OES). Moreover, all statistical analyses were
      performed using the SPSS statistical package according to Shapiro-Wilk test for
      normality, One Way ANOVA (Duncan Multiple Range Test), Independent t-test and
      Pearson's correlations. Results: The mean concentrations (MUg/kg) of Cd, Cu, Pb
      and Zn in raw milk samples were 0.36+/-0.28, 9.77+/-3.91, 32.83+/-20.80 and
      253.70+/-87.96, respectively and in the pasteurized milk samples were 5.57+/
      9.33, 8.41+/-5.99, 25.54+/-26.50 and 90.12+/-91.52, respectively. HRI values in
      adults and children via consumption of raw and pasteurized cow's milk were within
      the safe limits (HRI < 1). Conclusion: Considering the serious contamination of
      some samples of raw and pasteurized milk by Cd, Pb and Zn, a control of heavy
      metals content during the whole production processing of milk must be applied.

PMID- 30186789
TI  - Body Mass Index and the Literacy on Obesity in Relation to Media Following.
AB  - Background: The aim of this study was to investigate the effects of TV,
      magazines, radio, and internet following on body mass index (BMI) and obesity
      related literacy among adults. Methods: In this cross-sectional study, the
      subjects were recruited from an outpatient center in the city of Sombor, Serbia
      during Mar-Apr 2013. We collected data by a questionnaire from 657 (397 women;
      59%) subjects, aged from 18 to 87 yr (Mean = 45; SD =14). The questionnaire
      consisted of personal data, body height and weight, frequency of television,
      radio, magazines and internet following and personal opinion on the impact of
      smoking, alcohol consumption, stress and physical inactivity on obesity. Results:
      Spearman's rank correlation analysis showed that BMI increased with longer TV
      viewing with a very weak strength of the correlation (r=0.104; P=0.009) and
      decreased with more internet following with a weak strength of the correlation
      (r=-0.200: P<0.001). Multiple linear regression analysis revealed that only
      internet use had a significant independent effect on BMI. The frequency rise of
      internet following from "rare" to "often" and "every day" decreased BMI by 0.5
      per each grade. Internet followers showed a significantly better knowledge of the
      importance of smoking (P = 0.003), alcohol consumption (P<0.001) and physical
      inactivity (P=0.004) for obesity in comparison to non-followers. Conclusion:
      Internet is the only media that independently and positively influence weight
      control and the literacy on obesity among adults.

PMID- 30186791
TI  - Determination of the Risk Factors That Influence Occurrence Time of Traffic
      Accidents with Survival Analysis.
AB  - Background: This study aimed to determine risk factors that occurrence time of
      traffic accidents. Traffic accident occurrence time is defined as the time
      between a driver's getting his/her license and having the first accident,
      involving death or injury between 2008-2012 and there were investigated. Methods:
      This study was conducted with the Cox Regression and life tables models included
      among survival analysis models. Data of all 11.671 traffic accidents in Kayseri
      in Turkey were analyzed for the 5-yr period. Results: The non-occurrence rate of
      traffic accidents involving injury is mostly affected by gender, age, education,
      number of vehicles involved in accident, road surface material, daylight, type of
      road, direction of road and time of the day. The non-occurrence rate of fatal
      traffic accident duration is mostly affected by gender, age, education, daylight
      and horizontal alignment. The rate of having an accident involving death or
      injury after getting driver's license is 30.3% in the first 5 yr, it is 50.1% in
      the first 10 yr and 91.7% in 25 yr. Conclusion: As the non-occurrence time
      increases, occurrence of accidents in earlier years will decrease. In other
      words, the number of accidents in earlier years will be lower. This will cause a
      decrease in the number of accidents in total.

PMID- 30186792
TI  - Developmental and Psychometric Properties of a Belief-based Reproductive Health
      Behavior Questionnaire for Female Adolescents.
AB  - Background: The aim of this study was to develop and evaluate the psychometric
      properties of a questionnaire for the measurement of reproductive health among
      female adolescents in Iran. Methods: This cross-sectional study was conducted
      among 289 female students aged 12-15 yr in Tehran, Iran from 2015-2016. The
      participants were selected using multi-stage random cluster sampling. In
      addition, the Belief-Based Reproductive Health Questionnaire (BBRHQ) was designed
      using the properties of the Theory of Planned Behavior (TPB). Results:
      Exploratory factor analysis of 104 items identified a six-factor solution. These
      factors jointly accounted for 67% of the observed variance of outcome variable.
      The confirmatory factor analysis indicated a good fit to the data. In addition,
      the Cronbach's alpha coefficient showed an excellent internal consistency
      (alpha=0.92). Conclusion: Belief-Based Reproductive Health Questionnaire (BBRHQ)
      is a valid and reliable instrument for measurement of reproductive health
      behaviors of adolescents.

PMID- 30186794
TI  - Comment on "Molecular Characterization of Animal Fasciola spp. Isolates from
      Kermanshah, Western Iran".

PMID- 30186793
TI  - Psychological Needs, Satisfaction and Intention to Migrate in Iranian Nurses: A
      Qualitative Content Analysis.
AB  - Background: The shortage of nurses is a global health problem and one of the main
      challenges for healthcare systems throughout the world including Iran. One of
      factors that affect the migration trends is psychological needs satisfaction.
      This study aimed at identifying the psychological factors which persuade Iranian
      nurses to migrate and suggesting necessary measures in this regard. Methods: This
      qualitative study was conducted through a traditional content analysis approach
      on 20 working Iranian nurses who are migrating to other countries between 2015
      and 2017. Data were collected through interviews and observation in different
      wards of hospitals in Iran. Data were written and analyzed after reduction,
      naming them, obtaining analytical codes, and identifying the categories and
      subcategories using traditional method. Results: Three main categories in
      relation to satisfaction of the psychological needs and reasons for migration
      were obtained after data analysis. The first category was "authority" with two
      subcategories of independent decision-making power and being unconsidered, the
      second category was "social support" with three subcategories of communication
      with health team members, communication with nurse colleagues, and communication
      with nurse managers, and the third category was "job promotion" with four
      subcategories of addressing the routines, nurse role, job promotion
      opportunities, and teaching organizational environment. Conclusion: Identifying
      problems and obstacles to achieve the goal is the first step to solve the
      problem. This study provided further and clearer understanding of psychological
      causes regarding decision of nurses to migrate to developed countries, and nurses
      noted that the decision to migrate is in the search to meet their psychological
      needs.

PMID- 30186795
TI  - Response Letter to the Editor in Reference to Letter to the Editor about
      "Molecular Characterization of Animal Fasciola spp. Isolates from Kermanshah,
      Western Iran".

PMID- 30186796
TI  - The Influence of Total Quality Recovery in Perceived Enjoyment during Football
      Specific Training.

PMID- 30186797
TI  - Citizens Attitudes about the Emergency Situations Caused by Epidemics in Serbia.

PMID- 30186798
TI  - The Structure of a Daily Food Ration of the Inhabitants Over 40 Years Old in the
      Republic of Kazakhstan.

PMID- 30186799
TI  - The Most Common Side Effects Experienced by Patients Were Receiving First Cycle
      of Chemotherapy.

PMID- 30186800
TI  - The High Prevalence of Osteoporosis as a Preventable Disease: The Need for
      Greater Attention to Prevention Programs in Iran.

PMID- 30186801
TI  - Well-being in Hemodialysis Patients.

PMID- 30186802
TI  - Disability and Happiness in Iran: What Can We Do?

PMID- 30186803
TI  - Arbitrary Use of Insulin and Its Consequence.

PMID- 30186804
TI  - Does "Overall Catastrophic Health Care Expenditure" Make Sense?

PMID- 30186805
TI  - Response Letter to the Editor in Reference to Letter to the Editor about "Does
      Overall Catastrophic Health Care Expenditure Make Sense"?

PMID- 30186806
TI  - The Turning Point of China's Rural Public Health during the Cultural Revolution
      Period: Barefoot Doctors: A Narrative.
AB  - Background: According to Mao Zedong's orders, the Communist Party of China made
      efforts to perform the system of 'barefoot doctors' even during the political
      mayhem of the Cultural Revolution. This pioneering medical system made a great
      contribution to medical services for rural communities and the public health
      system from 1960s to 1970s. Attracting new attention in the beginning of the 21st
      century, the barefoot doctor system influenced the formation of the Chinese
      medical system of unique structure. Methods: Utilizing and analyzing the
      currently existing research outcomes on 'barefoot doctors', we investigated the
      two overlooked characteristics in the Chinese medical system originated from the
      barefoot doctor system; i) why the barefoot doctor system attracts new attention
      in the 21st century and ii) why and how Western and Chinese medicine could
      systematically be combined, which is the unique phenomenon in the world. Results:
      The barefoot doctor system satisfied the Chinese government's political aims and
      realistic request under the banner of Cultural Revolution simultaneously. In
      reality, this system gratified prevention-oriented modernized public health
      policy, reducing serious gap of medical services between cities and rural areas.
      Yet, this leading system was abolished in 1980s without timely use. Conclusion:
      In the present, the barefoot doctor system is holding limelight again as a
      successful precedent to intensify preventive public health service all over
      China, especially for underdeveloped areas. Moreover, Chinese medicine-friendly
      stance to utilize 'doctors of Chinese medicine', absolute majority over those of
      Western medicine, created the uniqueness of integrative medicine.

PMID- 30186807
TI  - Trend of Daily Sports Participation in Korean Aged Population and Sports Policy:
      A Review of Research on Public Daily Sports Participation.
AB  - Background: This study aimed to investigate the trend of physical activity and
      daily sports participation in the Korean aged population through the review of
      'Research on Public Daily Sports Participation' published by the Ministry of
      Culture, Sports and Tourism. The main purpose was to suggest the best health and
      sports policy for the future. Methods: The result of the research conducted by
      the government was published 13 times in total from 1989 to 2015. The aged were
      defined as people in their 60s and 70s since 2006. Based on the research
      published 7 times from 2006 to 2015, this study analyzed the changes and the
      trend recognition of health status, physical activities, sports activity effects
      and environment in the aged population in South Korea. Results: Majority of the
      aged population was found to hardly recognize their health status, but positively
      aware of physical and sports activity effect, particularly that the sports
      facility environment has been improving. Therefore, it is encouraged to set up
      elderly-friendly routine sports environment to motivate their participation and
      consequently establish healthy exercise culture. Conclusion: This study has great
      significance as it suggests the direction of future health and sports policy by
      analyzing the trend of previous physical activities and daily sports
      participation among the aged population based on the government-published
      research.

PMID- 30186809
TI  - Assessing the Values of Blueberries Intake on Exercise Performance, TAS, and
      Inflammatory Factors.
AB  - Background: The purpose of this study was to determine the effect of blueberry
      supplementation on exercise performance time, inflammation markers, energy
      substrates, insulin, and TAS levels during two periods: non-supplemented period
      and supplemented period. Methods: Eight young active participants were recruited
      from the Department of Physical Education at some universities in Busan City,
      Republic of Korea. The test period was divided into two Sections: non
      supplemented period and supplemented period. Vo2 max and exercise performance
      time of participants were measured, with or without blueberry supplementation,
      with a portable gas analyzer and ECG, respectively. Results: Vo2 max and exercise
      performance time were increased in the blueberry supplementation period. IL-6 and
      CRP levels were significantly lowered in blueberry supplementation period
      following exercise. Conclusion: The blueberry supplementation can potentially
      increase the exercise performance and decrease the IL-6 and CRP levels caused by
      an increased TAS level.

PMID- 30186808
TI  - Association between Cigarette Smoking Frequency and Health Factors among Korean
      Adults.
AB  - Background: Recently, there has been a trend that cigarette smoking rate in Asian
      and Africa adults has increased while the age group to start smoking has
      decreased gradually. This study aimed to investigate the relationships between
      lifetime smoking and hypertension, diabetes, obesity, waist measure, fasting
      blood pressure and food consumption, in order to look into health status
      depending on smoking status in Koreans. Methods: Totally, 1075 men and 697 women
      with no disease participated in this study, in which one-way ANOVA was conducted
      by using SPSS version 18.0 for statistical process. The level of statistical
      significance was 0.05. Results: As a result of analysis on relationship between
      lifetime smoking and hypertension, obesity and diabetes, statistically
      significant differences were revealed.Lifetime smoking was found to be
      significantly associated with increased waist measure, higher level of fasting
      blood sugar, and more ingestion of nutrients (carbohydrate, fat, and protein).
      Conclusion: Increased amount of lifetime cigarette smoking was shown to
      negatively influence various health factors, which might become to be a drive to
      cause diseases. Therefore, method to improve health factors must be sought for
      via education and campaign to control an amount of cigarette smoking in Korean
      adults.

PMID- 30186810
TI  - Assessing the Impact of Aging on Burden of Disease.
AB  - Background: In this study, we presented a theoretical model to measure aging rate
      in OECD countries, quantitatively measuring the effect of aging rate on disease
      patterns in each country and explaining how these effects were obtained. The
      purpose of this study was to investigate how disease burden varies according to
      the level of medical infrastructure and changes in aging index using OECD aging
      data and WHO disease burden data. Methods: This study used OECD Health data and
      global burden of disease data from the WHO in 2000 and 2012. We applied a
      difference-in-differences (DID) model was used to analyze effects of aging.
      Results: Disease burdens increased over time, especially in the aging population
      of middle-aged. In the case of loss of life due to premature death, the number of
      middle-aged and older population was increased significantly. When we examined
      the econometric model after controlling related factors, there was a significant
      increase in loss of life due to illness and premature death. On the other hand,
      the group of piles at the aging level had a significant positive effect on Years
      of Life Lost (YLL). Although the interaction effect as an important variable
      showing double difference effect of aging did not affect Disability adjusted Life
      Year (DALY), it showed a significant positive effect on YLL. Conclusion: Loss of
      life due to death of the elderly was relatively higher than that of the elderly.
      Therefore, the impact of population aging on medical resources and medical
      expenditures in the future should consider population structure changes, disease
      burden by age group, and interactions of these two incremental factors.

PMID- 30186811
TI  - Factors Related to the Attitude of North Korean Refugees Towards People with
      Mental Illness.
AB  - Background: The purpose of this study was to explore the level of mental health
      knowledge among North Korean refugees residing in South Korea and to analyze the
      factors related to their attitude towards people with mental disorders. Methods:
      The survey was conducted on 150 people and the analysis included results from 138
      participants in 2013. A multiple linear regression analysis was conducted to
      analyze the factors related to the attitude towards people with mental illness.
      Results: The education level attained in South Korea and the duration of stay in
      the South were effective factors associated with anti-authoritarianism. Age,
      marital status, education level in the North, and level of mental health
      knowledge were significant factors for benevolence. Time spent in South Korea and
      knowledge of mental health played a significant role in determining their
      attitude towards social restrictiveness (P=0.014). Conclusion: The knowledge of
      mental illness in refugees was associated with their attitude towards people with
      mental illness. This study suggests the need to educate refugees on mental
      illness to enhance their attitudes.

PMID- 30186812
TI  - Behaviors and Culture of Drinking among Korean People.
AB  - Background: The objective of this study was to identify behaviors and culture of
      drinking alcohol in Korean people. Methods: Among a panel of subjected enrolled
      in existing domestic survey companies, adults aged 19 to 59 yr old who replied
      that their drinking frequency was more than once a month for the past one year
      were selected in 2017. Sample size and methods used for analysis were determined
      by considering demographically proportioned stratified sampling and monthly
      alcohol drinking rate. A total of 1,185 subjects (731 males and 454 females)
      responded to questionnaires. Results: Most drinking behaviors were in the domain
      of leisure time. Drinking for two or more times a month and binge drinking were
      mainly concentrated in five occasions types: going out with friends (44.2%),
      going out with colleague (34.2%), drinking at home or friend's home with friends
      (32.9%), drinking at home alone (29.3%), and drinking with meals at home (27.5%).
      Regarding the ratio of experiences in drinking for subjects according to
      occupations, 'Directors/Managers' who participated in receptions of guests,
      either hosted by or invited thereto, had the highest percentage (64.2%), followed
      by 'Individual Proprietors' (56.4%). Differences between each type of occupation
      were found to be statistically significant (P< 0.001). Conclusion: The drinking
      culture in Korea was characterized by more social drinking than by drinking alone
      at home. The drinking behavior was often one-shot at a time rather than drinking
      a little sip. The practices of collective drinking should be improved to avoid
      secondary harmful effects.

PMID- 30186813
TI  - A Comparative Study on Acceptance and Distribution of Modern Medical Care in
      Japanese Colonies.
AB  - Background: The propagation of modern medicine in the colonies has often been
      described in terms of modernism and nationalism, focusing on the action-reaction
      conflict with colonial power, but the propagation of modem medical care and
      hygiene in colonial Chosun seems not to be explained by this perspective. So how
      can we explain this aspect? Answering this question could provide new
      implications for the many controversies surrounding the "colonial modern"
      acceptance. Methods: In order to examine the pattern of colonial acceptance of
      modern medicine, three cases of Britain and India, Japan and Taiwan, Japan and
      Chosun were set and compared, and the characteristics of colony Chosun were
      examined in-depth. Results: The existence of the 'traditional medicine doctors'
      who played an important role in the dissemination of public health in colonial
      Chosun can be explained from the understanding of the identity of Confucian
      intellectuals who played a role in the traditional Chosun society. Conclusion:
      The proliferation of modern medicine in the colonies has often been explained in
      terms of modernism and nationalism; however, the acceptance of a modern sanitary
      system in colony Chosun has been influenced by the traditional elements of the
      society. When considering these factors, the relationship between colonialists
      and the colonized society can be examined from a more interrelated perspective.

PMID- 30186814
TI  - Effects of Circuit Training According to the Feedback Type on Psychological and
      Physical Health of Workers with Social Anxiety Disorder.
AB  - Background: The effects of circuit training was investigated according to the
      feedback type on the psychological (social anxiety, anxiety, positive emotion)
      health and physical (body composition, physical fitness) health of social anxiety
      disorder workers. Methods: Sixty male workers in H Company in Seoul, South Korea
      with social anxiety disorder were divided into four groups (positive, negative,
      mixed, no feedback) by conducting a circuit training program in sport center of H
      company during 3 times per week, total 8 weeks from Feb 1st to Mar 31st, 2017.
      The results of the pre-test and post-test were analyzed as follows. Results: 1)
      In effect of social anxiety, there were significant differences in the positive,
      negative, and mixed feedback groups. 2) In the effect of anxiety, there were
      significant differences in the positive, negative, and mixed feedback groups. 3)
      In the effect of positive emotion, there were significant differences in the
      positive, negative, mixed, and no feedback groups. 4) In the effect of body
      composition, body fat mass and body fat percentage have significant differences
      in the positive, negative, mixed, and no feedback groups. And fat free mass has
      significant differences in the positive and mixed feedback groups. 5) In the
      effect of physical fitness, grip strength, wall squat, bending forward have
      significant differences in positive, negative, mixed, and no feedback groups.
      Conclusion: The circuit training program improves the social anxiety disorder and
      positively affects the psychological health and physical health of participants.
      To participate in continuous exercise, personal training should be accompanied by
      the correct feedback of the leader.

PMID- 30186816
TI  - Educational Policies of Martial Art and Health in Schools Implemented by Japanese
      Colonial Power (1931-1937).

PMID- 30186815
TI  - Effects of 12 Weeks of Combined Exercise on Heart Rate Variability and Dynamic
      Pulmonary Function in Obese and Elderly Korean Women.
AB  - Background: We investigated whether a combination of aerobic and resistance
      exercise administered over a period of 12 weeks enhanced heart rate variability
      (HRV) and dynamic pulmonary function (DPF) in obese and elderly Korean women.
      Methods: The study was conducted in 2016 in the Konkuk University (Seoul, Korea).
      The study participants included 20 older obese women [aged 66.4+/-0.8years; >30
      BMI and >30% in percent body fat]. The subjects were divided into a non-exercise
      group (n=10, control group; CON) and a combined exercise group (n=10,
      experimental group; EXP). Total power (TP), low frequency (LF), high frequency
      (HF), and LH/HF ratio were measured as frequency-domain methods. Salivary
      cortisol levels were analyzed by ELISA. The participants underwent dynamic
      pulmonary function (DPF) test. Results: The EXP group showed a significantly
      decrease in body weight (P=0.002) and % body fat (P<0.001) following 12 weeks of
      combined exercise training. The CON group revealed a significant increase in LF
      (P=0.011), LF/HF ratio (P<0.001), salivary cortisol (P=0.015) and decrease in HF
      (P=0.003). However, the EXP presented a significant decrease in LF (P=0.006) and
      salivary cortisol (P=0.046), and a significantly increase in MVV (P<0.001).
      Conclusion: Twelve wk of combined aerobic and resistance exercise improves heart
      rate variability, reducing mental stress in obese older women. In addition, the
      exercise program was found to be effective in reducing body fat and improving
      lung function in obese elderly women in East Asian countries with similar body
      composition and cultural patterns. Therefore, further collaborative research is
      needed to investigate obese older women in East Asian countries.

PMID- 30186817
TI  - Low Total Dose of Anti-Human T-Lymphocyte Globulin (ATG) Guarantees a Good
      Glomerular Filtration Rate after Liver Transplant in Recipients with
      Pretransplant Renal Dysfunction.
AB  - We aimed to evaluate the safety and efficacy of low doses of anti-T-lymphocyte
      globulin (ATG)-based immunosuppression in preserving renal function and
      preventing liver rejection in liver transplant (LT) recipients with pretransplant
      renal dysfunction. We designed a prospective single-center cohort study analyzing
      patients with pre-LT renal dysfunction defined as eGFR<60 mL/min/1.73m2, who
      underwent induction therapy with ATG (ATG group, n=20). This group was compared
      with a similar retrospective cohort treated with basiliximab (BAS group, n=20).
      An economic analysis between both induction therapies was also undertaken. In the
      ATG group, 45% and 50% of patients had recovered their renal function without
      acute cellular rejection (ACR) episodes at day 7 and 1 month after LT,
      respectively, versus 40% and 55% of patients in the BAS group (p=1). Renal
      function improved in both groups over time and no differences between groups were
      observed regarding one-year eGRF and one-year probability of ACR. Cost per
      patient of the ATG course was 403? (r: 126-756) versus 2,524? of the basiliximab
      course (p=0.001). In conclusion, induction with low dose of ATG or basiliximab in
      patients with pretransplant renal dysfunction is a good strategy for preserving
      posttransplant renal function; however the use of low-dose ATG resulted in a
      substantial reduction in drug costs. This trail is registered with
      ClinicalTrials.gov number: NCT01453218.

PMID- 30186818
TI  - Increased Duodenal Iron Absorption through Upregulation of Ferroportin 1 due to
      the Decrement in Serum Hepcidin in Patients with Chronic Hepatitis C.
AB  - Hepatic iron accumulation is generally increased in the chronic hepatitis C (CHC)
      liver; however, the precise mechanism of such accumulation remains unclear. We
      evaluated iron absorption from the gastrointestinal tract of patients with CHC
      and control participants. We measured the expression of a panel of molecules
      associated with duodenal iron absorption and serum hepcidin levels to determine
      the mechanism of iron accumulation in the CHC liver. We enrolled 24 patients with
      CHC and 9 patients with chronic gastritis without Helicobacter pylori infection
      or an iron metabolism disorder as control participants. An oral iron absorption
      test (OIAT) was administered which involved a dosage of 100 mg of sodium ferrous
      citrate. Serum level of hepcidin-25 was measured by liquid chromatography-tandem
      mass spectrometry. Ferroportin 1 (FPN) mRNA was measured by RT-PCR and FPN
      protein was analyzed by western blot. Samples were obtained from duodenum biopsy
      tissue from each CHC patient and control participant. Caco-2/TC7 cells were
      incubated in Costar transwells (0.4 MUm pores). The OIAT showed significantly
      greater iron absorption in CHC patients than control participants. Serum hepcidin
      25 in the CHC group was significantly lower than in the control group. Compared
      with control participants, duodenal FPN mRNA expression in CHC patients was
      significantly upregulated. The FPN mRNA levels and protein levels increased
      significantly in Caco-2/TC7 cell monolayers cultured in transwells with hepcidin.
      Lower serum hepcidin-25 levels might upregulate not only FPN protein expression
      but also mRNA expression in the duodenum and cause iron accumulation in patients
      with CHC.

PMID- 30186819
TI  - beta-Catenin Regulation in Sporadic Colorectal Carcinogenesis: Not as Simple as
      APC.
AB  - Background: The wnt/APC/beta-catenin pathway is a critical initiator in
      colorectal carcinogenesis in both hereditary and sporadic colorectal cancer
      (CRC). The progression of this process remains incompletely understood, although
      inflammation is pivotal. Drivers of inflammation are elevated in malignant tissue
      and have been shown to regulate beta-catenin expression. Interleukin-17A (IL-17A)
      is protumorigenic at elevated levels via COX-2 stimulation. Elevated peroxisome
      proliferator-activated receptor gamma (PPARgamma) expression has reduced risk of
      carcinogenesis and good overall prognosis in established CRC. Activation of
      PPARgamma has inhibitory effect on beta-catenin. Methods: Using qPCR and IHC, we
      compared beta-catenin, PPARgamma, COX-2, and IL-17A in the colonic mucosa of
      patients with sporadic CRC, inflammatory bowel disease (IBD), and irritable bowel
      syndrome (IBS), against a normal control population. Results: beta-catenin mRNA
      and protein expression progressively increased from the Normal group, through IBS
      and IBD reaching statistical significance in CRC. COX-2 mRNA levels increased
      similarly with statistical significance in IBD and CRC. However, COX-2 protein
      expression was inverted with significant expression in the Normal and IBS groups
      and reduced levels in IBD and CRC. PPARgamma mRNA expression was unchanged in IBD
      and CRC but was significantly elevated in the IBS. IL-17A mRNA was significantly
      reduced in IBS and CRC but unchanged in IBD. There were no differences in all
      parameters tested in the Normal and IBS groups. Conclusion: beta-catenin is
      confirmed as a major driver of colorectal carcinogenesis but is controlled by
      many more players other than APC. Elevated levels of PPARgamma may have an
      anticarcinogenic effect. The role of COX-2 expression, especially its
      posttranscriptional regulation in colorectal cancer, needs further elucidation.

PMID- 30186820
TI  - The Use of Biomarkers in Early Diagnostics of Pancreatic Cancer.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal solid
      malignancies with increasing incidence. The poor prognosis is due to the
      aggressive nature of the tumor, late detection, and the resistance to
      chemotherapy and radiotherapy. A radical surgery procedure is the only treatment
      that has been shown to improve the 5-year survival rate to 20-25%. However, the
      majority of patients (80-85%) are diagnosed with locally advanced or metastatic
      disease and just 15-20% patients are diagnosed in an early stage allowing them to
      undergo the potentially curative surgical resection. The early detection of PDAC
      without the use of invasive methods is challenging and discovery of a cost
      effective biomarker with high specificity and sensitivity could significantly
      improve the treatment and survival in these patients. In this review, we
      summarize current and newly examined biomarkers in early PDAC detection.

PMID- 30186821
TI  - Chronic Hepatitis C Association with Diabetes Mellitus and Cardiovascular Risk in
      the Era of DAA Therapy.
AB  - Patients with chronic hepatitis C have both higher prevalence of diabetes
      mellitus type 2 (T2DM) and increased cardiovascular risk compared to never
      infected people. Sustained viral response (SVR) achievement led to decreasing
      incidence and prevalence of T2DM during the interferon era of HCV treatment.
      Currently, direct-acting antiviral drugs (DAA) are the gold standard for treating
      HCV infection, while yielding SVR in nearly all patients. In chronic HCV patients
      with T2DM (prediabetes most likely too), DAA therapy is associated with both
      better fasting glucose and glycated hemoglobin (HbA1C) controls; thus reducing
      pharmacotherapy in a certain part of patients is possible. Papers mentioned in
      the review confirmed DAA role in both total cholesterol (TC) and low-density
      lipoprotein cholesterol (LDL-C) increase. This alteration was accompanied by an
      increase in high-density lipoprotein cholesterol (HDL-C) and a decrease in
      triglycerides (TG) verified by most of the studies. However, the clinical
      significance of lipoprotein alterations caused by DAA therapy has not been
      explained yet. Moreover, DAA treatment of chronic hepatitis C improves
      hypertension control and atherosclerotic plaques. It is very likely that DAA
      therapeutic regimens will decrease both T2DM prevalence and cardiovascular risk
      in chronic hepatitis C patients; further research, however, is needed.

PMID- 30186822
TI  - Predictive Value of a Noninvasive Serological Hepatic Fibrosis Scoring System in
      Cirrhosis Combined with Oesophageal Varices.
AB  - Objective: In recent years, the noninvasive serological scoring system has become
      a research hotspot in predicting hepatic fibrosis and has achieved good results.
      However, it has rarely been applied to the prediction of oesophageal varices. The
      aim of the study was to evaluate the predictive value of the four following
      scoring systems in cirrhosis combined with oesophageal varices: aspartate and
      platelet ratio index (APRI), aspartate aminotransferase-alanine aminotransferase
      ratio (AAR), FIB-4, and S index. Methods: A total of 153 patients with cirrhosis
      were categorized into groups with or without oesophageal varices. In addition,
      cirrhosis patients with oesophageal varices were further divided into mild,
      moderate, and severe grades. The rank sum test was used to compare the
      significant differences of APRI, AAR, FIB-4, and S index between the two groups
      of cirrhosis patients with or without oesophageal varices. A ROC curve was
      generated to compare the area under the curve of the three groups and to obtain
      the corresponding optimal prediction value. Moreover, multivariate logistic
      regression analysis was employed to assess the predictive factors for cirrhosis
      combined with oesophageal varices. Results: 44 patients had no oesophageal
      varices and 108 patients had oesophageal varices. Of the 108 patients with
      oesophageal varices, 43 were mild, 32 were moderate, and 33 were severe. The rank
      sum test indicated that the APRI, FIB-4, and S index were statistically
      significant between two groups (P < 0.05), while no significant difference was
      detected in terms of AAR between the two groups (P > 0.05). In addition, all four
      scoring systems were statistically significant between nonoesophageal varices
      group and severe oesophageal varices group (P < 0.05). In the ROC curve of
      oesophageal varices, the AUC values of APRI, FIB-4, and S index for predicting
      oesophageal varices were 0.681, 0642, and 0.673, respectively. However, in the
      ROC curve of severe oesophageal varices, the AUC values of APRI, AAR, FIB-4, and
      S index were 0.729, 0.648, 0.673, and 0.695, respectively. Multivariate logistic
      regression analysis indicated that APRI and FIB-4 were predictors of disease
      progression (P < 0.05). Conclusion: AAR harboured a poor predictive value for
      oesophageal varices, APRI can be used as a reference index for the prediction of
      severe oesophageal varices, and the S index harboured potential value in
      predicting the degree of progression of cirrhosis.

PMID- 30186823
TI  - Immunotherapy and Asthma in Children.
AB  - Allergen immunotherapy (AIT) is still the only disease-modifying treatment
      strategy for IgE-mediated allergic diseases, with consolidated evidence both in
      adults and children. AIT is effective in determining clinical improvement of
      allergic rhinitis and asthma, such as reduced symptoms, medication use, and
      improvement of quality of life, with a long-lasting effect after cessation of
      treatment. Results from recent clinical studies have implemented the evidence of
      effectiveness and safety of allergen immunotherapy for the treatment of allergic
      asthma, so that the current asthma guidelines now recommend sublingual
      immunotherapy as an add-on therapy for asthma in adults and adolescents with
      house dust mite allergy, allergic rhinitis, and exacerbations despite low-to
      moderate dose ICS, with forced expiratory volume in 1 second more than 70%
      predicted. AIT may also reduce the risk of progression from allergic rhinitis to
      asthma in children and prevent the onset of new sensitizations, thus representing
      a potentially preventive method of treatment. The aim of this review is to
      present an updated overview of the clinical indications of AIT, with particular
      reference to pediatric asthma, of the mechanisms of clinical and immunological
      tolerance to allergens, and of the potential biomarkers predicting clinical
      response.

PMID- 30186824
TI  - Interventions on Adherence to Treatment in Children With Severe Asthma: A
      Systematic Review.
AB  - Introduction: Poor adherence to inhaled medication is a commonly encountered
      problem among children with asthma. However, there is a relatively paucity of
      data regarding the adherence of children with severe asthma, as well as the merit
      of any interventions to improve this adherence. Objectives: The aim of this
      systematic review was to identify the available literature on the rate of
      adherence and the influence of interventions in improving adherence to controller
      inhaled medication, in children with severe asthma. Methods: A systematic
      literature search was performed in MEDLINE/PubMed, Cochrane Library, and Scopus
      databases. Studies were included in the present review if their target population
      were children and/or adolescents with severe asthma and presented data on
      medication adherence before and after a given intervention. Results: A total of
      seven studies, conducted in USA, Canada, and UK, and published between 2012 and
      2018, met the inclusion criteria. Adherence to controller medication was assessed
      via either objective or subjective measures (questionnaires), or a combination of
      them. Interventions included communication during pediatric visits and audio
      taped medical visits, individualized care programs, electronic monitoring
      devices, interactive website and peak-flow prediction with feedback. Adherence
      rates for the baseline (before intervention) or for the control groups ranged
      from 28 to 67%. In general, there was a significant improvement of adherence
      after intervention with rates increasing to 49-81%. Conclusion: Adherence rate in
      children with severe asthma is not satisfactory but it can be improved after
      proper interventions. Nevertheless, the heterogeneity among adherence assessment
      tools, and the variety of interventions, in combination with the lack of studies
      focusing on severe asthma, highlight the need for further research in this field.

PMID- 30186825
TI  - A Novel PCCA Mutation in a Patient With Late-Onset Propionic Acidemia Identified
      by Genetic Diagnosis Panel.
AB  - Background: Propionic acidemia (PA) is an extremely rare autosomal recessive
      disorder which is caused by the deficiency of propionyl-CoA carboxylase (PCC) and
      associated with pathogenic variants in PCCA or PCCB gene. Case Report: Detection
      of PA in neonates is possible using Propionyl carnitine (C3) analysis by tandem
      mass spectrometry (MS/MS) in dried blood spots (DBS). Here we report one patient
      with PA. C3 in this case was normal in the initial screening and recall check and
      only manifested as the slightly increase of C3/C2, 3-hydroxypropionate in urine
      was only slightly elevated. Then two pathogenic mutations (c.802C>T/c.827delG)
      were detected in the PCCA gene by Genetic diagnosis panel. Among them, the
      variation rs774738181 (c.802C>T) was present on the dbSNP database which appeared
      to be "Likely pathogenic" in GenBank dbSNP (100915068). c.827delG was a novel
      frameshift mutation, leading to p.Gly276ValfsX46 mutation of amino acid sequence
      in PCCA. The patient underwent 1 year of follow-up, had total of 7 times and
      remain asymptomatic whose blood ammonia and liver function were normal. When the
      child was 1 year of age (in May of 2017), C3 and 3-Hydroxypropionate sudden
      elevated significantly, that proved pathogenicity of c.802C>T and c.827delG.
      Conclusion: Two novel mutations (c. 802C>T and c.827delG) in PCCA gene may be
      associated with late-onset PA, expanding its mutational spectrum. Maybe there is
      relation between the severity of propionyl-CoA carboxylase (PCC) activity defects
      and different genotypes.

PMID- 30186826
TI  - Editorial: Evidence-Based Practices to Reduce Falls and Fall-Related Injuries
      Among Older Adults.

PMID- 30186827
TI  - Thermally-Induced Spin Crossover and LIESST Effect in the Neutral
      [FeII(Mebik)2(NCX)2] Complexes: Variable-Temperature Structural, Magnetic, and
      Optical Studies (X = S, Se; Mebik = bis(1-methylimidazol-2-yl)ketone).
AB  - Two new iron(II) neutral complexes of bis(1-methylimidazol-2-yl)ketone (Mebik)
      with molecular formula [FeII(Mebik)2(NCS)2] (1) and [FeII(Mebik)2(NCSe)2] (2)
      have been synthesized and characterized by magnetic measurements, single-crystal
      X-ray diffraction, and solid state UV-vis spectroscopy. The temperature dependent
      magnetic susceptibility measurements of crystalline samples of both compound show
      the occurrence of a gradual spin transition centered at T1/2 = 260 K and 326 K,
      respectively. The crystal structures of both compounds were determined at
      different temperatures, below and above the transition, in order to detect the
      structural changes associated with the spin transition. The main structural
      modifications, when passing from the low-spin to the high-spin form, consist of
      an important lengthening of the Fe-N(Mebik) and Fe-N (C-S/Se) distances (by ca.
      0.20 and 0.18 A, respectively) and a noticeable variation of the N-Fe-N angles,
      leading to a more distorted [Fe-N6] octahedron. The spin-transition phenomenon
      also affects the optical properties, with significant decrease of the intensity
      of the Metal-to-Ligand charge transfer band upon increasing the temperature.
      Finally, both complexes exhibit a light-induced excited spin-state trapping under
      laser light irradiation at low temperature. DFT calculations were also carried
      out on these complexes in order to rationalize the theoretically predicted
      magnetic and optical behavior with those of the experimental one. The results
      clearly highlights the dramatic alteration of the magneto-structural behavior of
      the tris-chelate [FeII(Mebik)3]2+ spin-crossover complex upon substituting one
      Mebik with NCS and NCSe ligands.

PMID- 30186828
TI  - UPLC-MS/MS Based Identification of Dietary Steryl Glucosides by Investigation of
      Corresponding Free Sterols.
AB  - Dietary plant foods are characterized by a vast molecular diversity of
      glycosylated sterols (SG) that differ in the structure of the steryl backbone.
      The identification of these polar steryl conjugates represents a major challenge
      as they are structurally highly similar, and commercial standards are limited to
      a few naturally abundant species. Spectral databases do not yet contain MS/MS
      spectra of these sterol conjugates obtained by electrospray ionization (ESI),
      which would facilitate their reliable identification. Thus, this study aimed at
      providing novel information on ESI-MS/MS spectra of both abundant and minor SG
      found in foods. As a first step, however, free sterols (FS) were investigated for
      their fragmentation behavior as they share the same intermediate ion as SG. Pure
      SG were obtained from commercially available standard mixtures and minor SG were
      extracted from different food sources (oat bran, wheat bran, pumpkin seeds,
      melon, rapeseeds, and potato peel). ESI-MS/MS spectra of 15 FS were assessed and
      fragment ions reflective of structural features were identified and rationalized.
      Subsequently, 14 SG were identified at four different levels, while relative
      retention times from chromatographic separation and spectral features of FS
      served to identify five SG. Spectral data from FS were directly transferable to
      SG when analyzed as aglycone ions as shown by similarity scores while SG were
      characterized by shorter retention times in reverse phase chromatography and the
      additional analysis as sodiated adduct confirmed their glycosidic nature.
      Moreover, we report for the first time the occurrence of 24-methylenecholesterol
      and a 4-monomethyl sterol as glycosidic conjugates in higher plants. The
      presented data will serve as a valuable tool for SG profiling of foods by
      facilitating their identification.

PMID- 30186829
TI  - Advantage of a Narrow Spectrum Host Defense (Antimicrobial) Peptide Over a Broad
      Spectrum Analog in Preclinical Drug Development.
AB  - The APO-type proline-arginine-rich host defense peptides exhibit potent in vitro
      killing parameters against Enterobacteriaceae but not to other bacteria. Because
      of the excellent in vivo properties against systemic and local infections,
      attempts are regularly made to further improve the activity spectrum. A C
      terminal hydrazide analog of the Chex1-Arg20 amide (ARV-1502) shows somewhat
      improved minimal inhibitory concentration against Moraxellaceae. Here we compared
      the activity of the two peptides as well as an inactive dimeric reverse amide
      analog in a systemic Acinetobacter baumannii infection. Only the narrow spectrum
      amide derivative reduced the 6-h blood bacterial burden by >2 log10 units
      reaching statistical significance (p = 0.03 at 5 mg/kg and 0.031 at 2 mg/kg
      administered intramuscularly). The hydrazide derivative, probably due to stronger
      activity on cell membranes, lysed erythrocytes at lower concentrations, and
      caused toxic effects at lower doses (10 mg/kg vs. 25 mg/kg). In a limited study,
      the amide induced a >5-fold production of the anti-inflammatory cytokine IL-10
      over untreated naive mice and minor increases in the anti-inflammatory IL-4 and
      pro-inflammatory cytokines TNF-alpha and IL-6, in blood. The blood of hydrazide
      treated mice exhibited significantly lowered levels of IL-10 and slightly
      decreased IL-4 and TNF-alpha. These results suggest that the improved efficacy of
      the narrow-spectrum amide analog is likely associated with increased anti
      inflammatory cytokine production and better stimulation of the immune system.
      Although blood IL-6 and TNF-alpha levels are frequently used as markers of
      potential toxicity in drug development, we did not observe any notable increase
      in mice receiving the toxic polyamide antibiotic colistin.

PMID- 30186830
TI  - Multi-Tasking POM Systems.
AB  - Polyoxometalate (POM)-based materials of current interest are summarized, and
      specific types of POM-containing systems are described in which material
      facilitates multiple complex interactions or catalytic processes. We specifically
      highlight POM-containing multi-hydrogen-bonding polymers that form gels upon
      exposure to select organic liquids and simultaneously catalyze hydrolytic or
      oxidative decontamination, as well as water oxidation catalysts (WOCs) that can
      be interfaced with light-absorbing photoelectrode materials for
      photoelectrocatalytic water splitting.

PMID- 30186831
TI  - Fabrication of an AMC/MMT Fluorescence Composite for its Detection of Cr(VI) in
      Water.
AB  - Hexavalent chromium species, Cr(VI), which can activate teratogenic processes,
      disturb DNA synthesis and induce mutagenic changes resulting in malignant tumors.
      The detection and quantification of Cr(VI) is very necessary. One of the rapid
      and simple methods for contaminant analysis is fluorescence detection using
      organic dye molecules. Its application is limited owing to concentration
      quenching due to aggregation of fluorescent molecules. In this study, we
      successfully intercalated 7-amino-4-methylcoumarin (AMC) into the interlayer
      space of montmorillonite (MMT), significantly inhibited fluorescence quenching.
      Due to enhanced fluorescence property, the composite was fabricated into a film
      with chitosan to detect Cr(VI) in water. Cr(VI) can be detected in aqueous
      solution by instruments excellent, ranging from 0.005 to 100 mM with a detection
      limit of 5 MUM.

PMID- 30186832
TI  - Insights Into the Sunlight-Driven Water Oxidation by Ce and Er-Doped ZrO 2.
AB  - In the present work, the activity of Ce and Er-doped ZrO2 nanopowders for sun
      driven photocatalytic water oxidation has been investigated. ZrO2 powders with
      tunable amounts of tetragonal, monoclinic and cubic polymorphs have been
      synthesized by introducing Ce and Er (from 0.5 to 10 mol % on an oxide basis)
      through hydrothermal method. The aim of this work is to investigate the role of
      rare earth (RE) ions rich of electrons (Er3+) and with entirely empty levels
      (Ce4+) in the ZrO2 matrix for the sun-driven photocatalytic water oxidation
      reaction. The samples have been characterized by means of UV-Vis spectroscopy, X
      Ray diffraction (XRD), N2 adsorption, X-ray photoelectron spectrophotometry (XPS)
      and transmission electronic microscopy (TEM) with energy dispersive spectroscopy
      (EDS). With respect to the bare ZrO2 mainly containing monoclinic (m-) phase, an
      increasing amount of rare-earth (RE) dopant was found to improve the specific BET
      surface area and to stabilize the tetragonal (t-) or cubic (c-) polymorphs of
      ZrO2 at room temperature. XRD data confirmed that dopants were mainly inserted in
      the t-ZrO2 phase. The photocatalytic O2 evolution from water under AM 1.5 G
      simulated sunlight illumination of the prepared samples have been correlated with
      their optical, structural and chemical properties. The effect of the dopant
      concentration on the chemical-physical and photocatalytic properties of the Er-
      and Ce-doped ZrO2 materials was elucidated. The samples with 5% of RE oxide were
      the most active, i.e., three times more than pure zirconia. Their superior
      photocatalytic activity was found to be mainly correlated to two factors: (i) an
      optimal surface concentration of RE ions of about 3.7%, which increased charge
      carriers separation in the photocatalysts surface due more superficial defects of
      the t-ZrO2 and a higher surface area, thus enhancing the reaction kinetics, (ii)
      a controlled amount of monoclinic vs. tetragonal (or cubic) polymorphs of
      zirconia with an optimum ratio of about 70/30 of t-ZrO2/m-ZrO2. Instead, the
      increased ability of the RE-doped ZrO2 to harvest visible light was found to have
      a secondary role on the photocatalytic activity of the Ce-doped ZrO2 material.

PMID- 30186833
TI  - Mechanisms and Materials for NTE.
AB  - Negative thermal expansion (NTE) upon heating is an unusual property but is
      observed in many materials over varying ranges of temperature. A brief review of
      mechanisms for NTE and prominent materials will be presented here. Broadly there
      are two basic mechanisms for intrinsic NTE within a homogenous solid; structural
      and electronic. Structural NTE is driven by transverse vibrational motion in
      insulating framework-type materials e.g., ZrW2O8 and ScF3. Electronic NTE results
      from thermal changes in electronic structure or magnetism and is often associated
      with phase transitions. A classic example is the Invar alloy, Fe0.64Ni0.36, but
      many exotic mechanisms have been discovered more recently such as colossal NTE
      driven by Bi-Ni charge transfer in the perovskite BiNiO3. In addition there are
      several types of NTE that result from specific sample morphologies. Several
      simple materials, e.g., Au, CuO, are reported to show NTE as nanoparticles but
      not in the bulk. Microstructural enhancements of NTE can be achieved in ceramics
      of materials with anisotropic thermal expansion such as beta-eucryptite and
      Ca2RuO4, and artificial NTE metamaterials can be fabricated from engineered
      structures of normal (positive) thermal expansion substances.

PMID- 30186834
TI  - Corrigendum: Introgression of Physiological Traits for a Comprehensive
      Improvement of Drought Adaptation in Crop Plants.
AB  - [This corrects the article DOI: 10.3389/fchem.2018.00092.].

PMID- 30186836
TI  - Commercial Scale Manufacturing of Allogeneic Cell Therapy.
AB  - Allogeneic cell therapy products are generating encouraging clinical and pre
      clinical results. Pluripotent stem cell (PSC) derived therapies, in particular,
      have substantial momentum and the potential to serve as treatments for a wide
      range of indications. Many of these therapies are also expected to have large
      market sizes and require cell doses of >=109 cells. As therapeutic technologies
      mature, it is essential for the cell manufacturing industry to correspondingly
      develop to adequately support commercial scale production. To that end, there is
      much that can be learned and adapted from traditional manufacturing fields. In
      this review, we highlight key areas of allogeneic cell therapy manufacturing,
      identify current gaps, and discuss strategies for integrating new solutions. It
      is anticipated that cell therapy scale-up manufacturing solutions will need to
      generate batches of up to 2,000 L in single-use disposable formats, which
      constrains selection of currently available upstream hardware. Suitable
      downstream hardware is even more limited as processing solutions from the
      biopharmaceutical field are often not compatible with the unique requirements of
      cell therapy products. The advancement of therapeutic cell manufacturing
      processes to date has largely been developed with a cell biology driven approach,
      which is essential in early development. However, for truly robust and
      standardized production in a maturing field, a highly controlled manufacturing
      engineering strategy must be employed, with the implementation of automation,
      process monitoring and control to increase batch consistency and efficiency.

PMID- 30186837
TI  - Combined Use of Ninjin'yoeito Improves Subjective Fatigue Caused by Lenalidomide
      in Patients With Multiple Myeloma: A Retrospective Study.
AB  - Lenalidomide is an immunomodulating derivative of thalidomide, which shows anti
      tumor activity against myeloma cells with immunomodulation including augmentation
      of T-cell and natural killer cell function. Continuous treatment with this agent
      shows better survival benefit in patients with multiple myeloma and combined
      lenalidomide with dexamethasone (LEN-DEX) is a standard treatment regimen.
      However, fatigue is a frequent symptom resulting from lenalidomide
      administration. This side-effect therefore reduces quality of life for elderly
      patients and, furthermore, is a reason for treatment discontinuation.
      Unfortunately, appropriate preventive countermeasures against lenalidomide
      related fatigue have not been established. Ninjin'yoeito is a traditional Chinese
      medicine made from the extracts of 12 herbal plants, which positively affects
      immunity and inflammation. It is used to treat fatigue, decreased appetite,
      anemia, and general malaise associated with malignant tumors and chemotherapy. We
      have previously reported that ninjin'yoeito significantly improved patients'
      subjective fatigue symptoms treated with melphalan-prednisone for multiple
      myeloma. In the present study, we assessed the benefits of ninjin'yoeito as a
      supplementary treatment for patients with myeloma, and its effect on lenalidomide
      treatment regime compliance. We retrospectively analyzed 36 cases of newly
      diagnosed or relapsed/refractory multiple myeloma. The study included patients
      receiving LEN-DEX with onset of general fatigue after lenalidomide administration
      (13 and 23 patients with or without ninjin'yoeito, respectively). Frequency of
      subjective fatigue was significantly decreased in patients administered
      ninjin'yoeito, compared to those treated with LEN-DEX alone (92.3 and 47.8 % of
      patients with and without ninjin'yoeito, respectively; p = 0.008). In addition,
      combined use of ninjin'yoeito and LEN-DEX showed a trend toward reduced rates of
      treatment discontinuation (7.7 % and 34.8 % of patients with and without
      ninjin'yoeito, respectively; p = 0.076). Our results suggest that ninjin'yoeito
      is an effective method for treating subjective fatigue caused by lenalidomide and
      may have the potential to extend lenalidomide treatment duration.

PMID- 30186835
TI  - Multiplexed CRISPR/Cas9 Targeting of Genes Implicated in Retinal Regeneration and
      Degeneration.
AB  - Thousands of genes have been implicated in retinal regeneration, but only a few
      have been shown to impact the regenerative capacity of Muller glia-an adult
      retinal stem cell with untapped therapeutic potential. Similarly, among nearly
      300 genetic loci associated with human retinal disease, the majority remain
      untested in animal models. To address the large-scale nature of these problems,
      we are applying CRISPR/Cas9-based genome modification strategies in zebrafish to
      target over 300 genes implicated in retinal regeneration or degeneration. Our
      intent is to enable large-scale reverse genetic screens by applying a multiplexed
      gene disruption strategy that markedly increases the efficiency of the screening
      process. To facilitate large-scale phenotyping, we incorporate an automated
      reporter quantification-based assay to identify cellular degeneration and
      regeneration-deficient phenotypes in transgenic fish. Multiplexed gene targeting
      strategies can address mismatches in scale between "big data" bioinformatics and
      wet lab experimental capacities, a critical shortfall limiting comprehensive
      functional analyses of factors implicated in ever-expanding multiomics datasets.
      This report details the progress we have made to date with a multiplexed
      CRISPR/Cas9-based gene targeting strategy and discusses how the methodologies
      applied can further our understanding of the genes that predispose to retinal
      degenerative disease and which control the regenerative capacity of retinal
      Muller glia cells.

PMID- 30186838
TI  - Predicting Disease Progression and Mortality in Aortic Stenosis: A Systematic
      Review of Imaging Biomarkers and Meta-Analysis.
AB  - Background: Detecting among patients with aortic stenosis (AS) those who are
      likely to rapidly progress, yet potentially benefiting from prophylactic aortic
      valve replacement, is needed for improved patient care. The objective of this
      study was to evaluate the role of imaging biomarkers in predicting the
      progression to clinical symptoms and death in patients with AS. Methods: We
      searched the Pubmed and the International Clinical Trials Registry Platform
      databases for studies including patients with AS, and investigating imaging
      techniques, published in any language until Jan 1, 2018. Eligible sets of data
      include effect of imaging biomarkers relative to: (1) Overall mortality, (2)
      Cardiac mortality, and (3) Overall events (Symptom onset and Major Adverse
      Cardiovascular Events). Meta-analysis was used to examine associations between
      the imaging biomarkers and outcomes of AS using Random Effect models. Results:
      Eight studies and 1,639 patients were included after systematic review. Four
      studies investigated aortic valve calcification (AVC) whereas the remaining
      investigated biomarkers provided by cardiac magnetic resonance (CMR). Four
      articles investigated the presence of midwall fibrosis on late-gadolinium
      enhancement imaging, three reported its extent (LGE%) and two, the myocardial
      extracellular volume (ECV). By decreasing strength of association, there were
      significant associations between cardiac mortality and LGE% [Relative Risk (RR) =
      1.05, 95% Confidence Interval (CI) 1.01-1.10]; overall mortality and AVC (RR =
      1.19, 95%CI: 1.05-1.36); overall events and ECV (RR = 1.68, 95%CI: 1.17-2.41);
      cardiac mortality and midwall fibrosis (RR = 2.88, 95%CI: 1.12-7.39). Conclusion:
      AVC and myocardial fibrosis imaging biomarkers predict the outcomes in AS, and
      help understanding AS pathophysiology and setting therapeutic targets.

PMID- 30186839
TI  - Extracellular Vesicles as Biomarkers in Cardiovascular Disease; Chances and
      Risks.
AB  - The field of extracellular vesicles (EV) is rapidly expanding, also within
      cardiovascular diseases. Besides their exciting roles in cell-to-cell
      communication, EV have the potential to serve as excellent biomarkers, since
      their counts, content, and origin might provide useful information about the
      pathophysiology of cardiovascular disorders. Various studies have already
      indicated associations of EV counts and content with cardiovascular diseases.
      However, EV research is complicated by several factors, most notably the small
      size of EV. In this review, the advantages and drawbacks of EV-related methods
      and applications as biomarkers are highlighted.

PMID- 30186840
TI  - Clinical Features and Computed Tomography Findings Are Utilized to Characterize
      Retrobulbar Disease in Dogs.
AB  - The objective of this study is to describe the clinical features and computed
      tomography (CT) findings of dogs with retrobulbar disease. There are two facets
      to this study: a retrospective case series in which findings of dogs with primary
      vs. secondary retrobulbar disease are described, and a retrospective cross
      sectional study in which computed tomography findings of dogs with retrobulbar
      neoplasia vs. infection/inflammation are described and compared. The medical
      records of 66 client-owned dogs diagnosed with retrobulbar disease between 2006
      and 2016 were reviewed. Clinical information including signalment, the specialty
      service to which the dog was presented, clinical signs, physical examination
      findings, diagnostic results, treatment, and outcome were documented. Diagnostic
      imaging and histopathology were reviewed. Forty-one dogs (62.1%) were diagnosed
      with primary disease of the retrobulbar space; 25 dogs (37.9%) were considered to
      have secondary retrobulbar disease. Of the 41 dogs with primary retrobulbar
      disease, 19 were diagnosed with neoplasia, 19 with infectious/inflammatory
      disease, and 3 suffered traumatic insult to the retrobulbar space. Of the 25 dogs
      with secondary retrobulbar disease, 21 were diagnosed with neoplasia, 3 with
      infectious/inflammatory disease, and 1 with a cyst. Dogs had a combination of
      ocular, oral, and/or nasal clinical signs. CT findings of orbital osteolysis,
      orbital periosteal reaction, and presence of a retrobulbar mass were
      significantly associated with neoplasia, while zygomatic salivary gland
      enlargement, retrobulbar mass effect, and mandibular lymphadenopathy were more
      often associated with infectious/inflammatory disease. CT findings overlap among
      different retrobulbar diseases, but new bone formation and lysis are more often
      associated with neoplasia. Disease originating from the retrobulbar space was
      equally likely to be infectious/inflammatory (n = 19) or neoplastic (n = 19),
      based on definitive diagnostic results of dogs with primary retrobulbar disease.
      Due to the clinical ramifications of these disorders, the diagnosis and treatment
      of these cases should be managed with a multi-specialty approach.

PMID- 30186841
TI  - A Framework to Assess the Impact of New Animal Management Technologies on
      Welfare: A Case Study of Virtual Fencing.
AB  - To be ethically acceptable, new husbandry technologies and livestock management
      systems must maintain or improve animal welfare. To achieve this goal, the design
      and implementation of new technologies need to harness and complement the
      learning abilities of animals. Here, from literature on the cognitive activation
      theory of stress (CATS), we develop a framework to assess welfare outcomes in
      terms of the animal's affective state and its learned ability to predict and
      control engagement with the environment, including, for example, new
      technologies. In CATS, animals' perception of their situation occurs through
      cognitive evaluation of predictability and controllability (P/C) that influence
      learning and stress responses. Stress responses result when animals are not able
      to predict or control both positive and negative events. A case study of virtual
      fencing involving avoidance learning is described. Successful learning occurs
      when the animal perceives cues to be predictable (audio warning always precedes a
      shock) and controllable (operant response to the audio cue prevents receiving the
      shock) and an acceptable welfare outcome ensues. However, if animals are unable
      to learn the association between the audio and shock cues, the situation retains
      low P/C leading to states of helplessness or hopelessness, with serious
      implications for animal welfare. We propose a framework for determining welfare
      outcomes and highlight examples of how animals' cognitive evaluation of their
      environment and their ability to learn relates to stress responses. New
      technologies or systems should ensure that predictability and controllability are
      not at low levels and that operant tasks align with learning abilities to provide
      optimal animal welfare outcomes.

PMID- 30186842
TI  - A One Health Evaluation of the University of Copenhagen Research Centre for
      Control of Antibiotic Resistance.
AB  - We applied the evaluation framework developed by the EU COST Action "Network of
      Evaluation of One Health" (NEOH) to assess the operations, supporting
      infrastructures and outcomes of a research consortium "University of Copenhagen
      Research Centre for Control of Antibiotic Resistance" (UC-CARE). This 4-year
      research project was a One Health (OH) initiative with participants from 14
      departments over four faculties as well as stakeholders from industry and health
      authorities aiming to produce new knowledge to reduce the development of
      antimicrobial resistance (AMR). This was a case study focusing on assessing
      beneficial and counter-productive characteristics that could affect the OH
      outcomes. The study was also used to provide feedback to NEOH about the
      evaluation framework. The framework and evaluation tools are described in the
      introduction paper of this special journal issue. Data for the evaluation were
      extracted from the funding research proposal, the mid-term UC-CARE project
      evaluation report and supplemented with opinions elicited from project
      participants and stakeholders. Here, we describe the underlying system, theory of
      change behind the initiative and adapted questions from the NEOH tools that we
      used for semi-open interviews with consortium members throughout the evaluation
      process. An online survey was used to obtain information from stakeholders. The
      NEOH evaluation tools were then used for the qualitative and quantitative
      evaluation of the OH characteristics of UC-CARE. Senior UC-CARE researchers were
      interested and willing to be interviewed. Young scientists were more difficult to
      engage in interviews, and only 25% of stakeholders answered the online survey.
      Interviewees mentioned that the main benefit of UC-CARE was an increased
      awareness and general understanding of AMR issues. All interviewees stated that
      the adopted OH approach was relevant given the complexity of AMR. However, some
      questioned the applicability, and identified potentially counter-productive
      issues mainly related to the information sharing, collaboration and working
      methods across the consortium. A more integrated project organization, more
      stakeholder involvement and time for the project, flexibility in planning and a
      dedicated OH coordinator were suggested to allow for more knowledge exchange,
      potentially leading to a higher societal impact.

PMID- 30186843
TI  - Characterization of Spleen Transcriptome and Immunity Against Avian
      Colibacillosis After Immunization With Recombinant Attenuated Salmonella Vaccine
      Strains.
AB  - Avian pathogenic Escherichia coli (APEC) causes extraintestinal infections in
      poultry. Vaccines targeting APEC in chickens have been partially successful, but
      many lack heterologous protection. Recombinant attenuated Salmonella vaccine
      (RASV) strains can induce broad immunity against Salmonella and be modified to
      deliver E. coli antigens. Along with vaccine characteristics, understanding the
      host response is crucial for developing improved vaccines. The objectives of this
      study were to evaluate host responses to vaccination with an RASV producing E.
      coli common pilus (ECP) and assess protection against APEC infection in chickens.
      Four-day-old White Leghorn chickens were unvaccinated or orally vaccinated and
      boosted 2 weeks later with RASV chi8025(pYA3337), RASV chi8025(pYA4428) carrying
      ecp operon genes, or a combination of chi8025(pYA3337) and chi8025(pYA4428)
      (Combo). To assess host responses, serum IgY and intestinal IgA antibody titers
      were measured, and spleen samples (n = 4/group) were collected from unvaccinated
      and Combo vaccinated 4-week-old chickens for RNA-seq. Vaccine protection
      potential against Salmonella and APEC was evaluated in vitro using bacterial
      inhibition assays. Five-week-old chickens were challenged via air sac with either
      an APEC O2 or O78 strain. E. coli was enumerated from internal organs, and gross
      colibacillosis lesions were scored at necropsy. RASV immunized chickens elicited
      anti-E. coli antibodies. The spleen transcriptome revealed that 93% (89/96) of
      differentially expressed genes (DEG) were more highly expressed in Combo
      vaccinated compared to unvaccinated chickens, with signal as the most
      significantly impacted category. RNA-seq analysis also revealed altered cellular
      and metabolic processes, response to stimulus after vaccination, and immune
      system processes. Six DEG including genes linked to transcription regulation,
      actin cytoskeleton, and signaling were highly positively correlated with antibody
      levels. Samples from RASV immunized chickens showed protection potential against
      Salmonella strains using in vitro assays, but a variable response was found for
      APEC strains. After APEC challenges, significant differences were not detected
      for bacterial loads or gross lesions scores, but chi8025(pYA3337) immunized and
      chi8025(pYA4428) immunized chickens had significantly fewer number of APEC-O2
      positive samples than unvaccinated chickens. This study shows that RASVs can
      prime the immune system for APEC infection, and is a first step toward developing
      improved therapeutics for APEC infections in chickens.

PMID- 30186845
TI  - Interstitial lung abnormalities and physical function.
AB  - Reductions in objectively measured physical function are associated with
      interstitial lung abnormalities http://ow.ly/azAW30kMhqv.

PMID- 30186844
TI  - Evaluation of the Epithelial Barrier Function and Ileal Microbiome in an
      Established Necrotic Enteritis Challenge Model in Broiler Chickens.
AB  - Necrotic enteritis (NE) is a recognized multifactorial disease that cost annually
      to the poultry industry around $2 billion. However, diverse aspects related to
      its presentation are not completely understood, requiring further studies using
      known induction experimental models. Therefore, the purpose of this study was to
      measure the changes occurring in performance, intestinal integrity and ileal
      microbiome using a previously established NE-challenge model. Chickens were
      assigned to a negative control group (NC) or a positive control group (PC). In
      the PC, broilers were orally gavaged with Salmonella Typhimurium (ST) (1 * 107
      cfu/chick) at day 1, Eimeria maxima (EM) (2.5 * 104 oocyst/chick) at day 18 and
      Clostridium perfringens (CP) (1 * 108 cfu/chick/day) at 23-24 days of age.
      Weekly, body weight (BW), body weight gain (BWG), feed intake (FI) and feed
      conversion ratio (FCR) were evaluated. Morbidity and mortality were determined
      throughout the study, and NE lesion scores were recorded at day 25. Additionally,
      blood and liver samples were collected to measure gut permeability as determined
      by levels of serum fluorescein isothiocyanate-dextran (FITC-d) and bacterial
      translocation (BT). Ileal contents were processed for 16S rRNA gene-based
      microbiome analysis. Performance parameters and intestinal permeability
      measurements were negatively impacted in the PC resulting in elevated serum FITC
      d and BT with a -6.4% difference in BWG. The NE lesion score in PC (1.97 vs.
      0.00) was significantly higher in comparison to NC, although there was no
      difference in mortality. The microbiome analysis showed a dramatic shift of ileal
      microbiomes in PC groups as compared to NC (ANOSIM: R = 0.76, P = 0.001). The
      shift was characterized by reduced abundance of the phylum Actinobacteria (P <
      0.01), and increased abundance of the genera Butyrivibrio, Lactobacillus,
      Prevotella and Ruminococcus in PC compared to NC (P < 0.05). Expectedly,
      Clostridium was found higher in PC (2.98 +/- 0.71%) as compared to NC (1.84 +/-
      0.36%), yet the difference was not significant. In conclusion, results of the
      present study showed the different intestinal epithelial and microbiological
      alterations occurring in an established NE-challenge model that considers
      paratyphoid Salmonella infections in young chicks as an important predisposing
      factor for presentation of NE.

PMID- 30186846
TI  - New drugs in thoracic oncology: needs and knowledge - an online ERS Lung Cancer
      Assembly survey.
AB  - In the last decade, systemic therapy for advanced lung cancer has become diverse,
      complex and personalised. These new therapies (monoclonal antibodies, tyrosine
      kinase inhibitors (TKIs) and immunotherapy) have a far different toxicity profile
      compared to chemotherapy. Furthermore, clinical indications and reimbursement
      criteria can vary across Europe. The aim of the present online survey was to
      assess the knowledge, views and challenges facing the European respiratory
      community in this rapidly changing field. A 15-question web survey was sent to
      all European Respiratory Society members through the Society's monthly electronic
      communication. A total of 315 questionnaires were completed. Most of the
      respondents were male (59.1%), were above 40 years of age (52.9%) and were
      working in university/academic hospitals (74.8%), the majority as pulmonologists
      (90%). Only 55% of the participants were aware of the legal processes for drug
      recognition. Except for epidermal growth factor receptor TKI, up to 38% did not
      know about the specific toxicities of anaplastic lymphoma kinase/ROS proto
      oncogene 1 TKIs, monoclonal antibodies and immune checkpoint inhibitors. Of the
      respondents, 92% showed an interest in an online platform reporting new drugs'
      toxicities. Despite a large amount of publicity and integration of new drugs into
      therapeutic algorithms and clinical guidelines, physicians taking care of lung
      cancer patients have a need for up-to-date information on systemic therapy
      toxicity management and legal constraints.

PMID- 30186847
TI  - Unexpected Genetic Cause in Two Female Siblings with High Myopia and Reduced
      Visual Acuity.
AB  - In daily life, myopia is a frequent cause of reduced visual acuity (VA) due to
      missing or incomplete optical correction. While the genetic cause of high myopia
      itself is not well understood, a significant number of cases are secondary to
      hereditary malfunctions or degenerations of the retina. The mechanism by which
      this occurs remains yet unclear. Two female siblings, 4 y and 2 y, respectively,
      from a consanguineous Pakistani family were referred to our department for
      reduced VA and strabismus. Both girls were highly myopic and hence were further
      examined using standard clinical tests and electroretinography (ERG). The latter
      confirmed confounded electrical coupling of photoreceptors and bipolar cells.
      Further inquiry and testing confirmed a similar condition for the father
      including impaired night vision, reduced VA, photophobia, and an equally
      characteristic ERG. Findings in the mother were unremarkable. Subsequent genetic
      analysis of autosomal recessive and X-linked genes for congenital stationary
      night blindness (CSNB) revealed a novel homozygous splice site mutation in
      CACNA1F in the two girls transmitted from both the father and the mother. While
      in males the above clinical constellation is a frequent finding, this report, to
      the authors' knowledge, is the first demonstrating biallelic mutations at the
      CACNA1F locus in females.

PMID- 30186848
TI  - Protein Arginine Methyltransferase 2 Inhibits Angiotensin II-Induced
      Proliferation and Inflammation in Vascular Smooth Muscle Cells.
AB  - Objectives: Protein arginine methyltransferase 2 (PRMT2) protects against
      vascular injury-induced intimal hyperplasia; however, little is known about the
      role of PRMT2 in angiotensin II (Ang II)-induced VSMCs proliferation and
      inflammation. This research aims to determine whether PRMT2 inhibits Ang II
      induced proliferation and inflammation of vascular smooth muscle cells (VSMCs).
      Materials and Methods: PRMT2 overexpression was used to elucidate the role of
      PRMT2 in Ang II-induced VSMCs proliferation and inflammation. Western blotting
      and reverse transcriptional PCR were adopted to detect protein and mRNA
      expression severally. Cell viability was evaluated by 3-(4,5-Dimethylthiazol-2
      yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay and cell cycle distribution by
      flow cytometry. Results: Ang II significantly reduced mRNA and protein levels of
      PRMT2 in VSMCs in time-dependent and dose-dependent manner. Results of PRMT2
      overexpression indicated that PRMT2 inhibited proliferation of VSMCs stimulated
      with 100 nmol/L Ang II for 24 hours. Furthermore, overexpression of PRMT2 reduced
      Ang II-induced production of proinflammatory cytokines such as interleukin 6 (IL
      6) and interleukin 1beta (IL-1beta) in VSMCs. Conclusions: These findings suggest
      that PRMT2 alleviates Ang II-induced VSMCs proliferation and inflammation,
      providing a new mechanism about how Ang II mediated VSMCs proliferation and
      inflammation.

PMID- 30186849
TI  - N-Linked Glycopeptide Identification Based on Open Mass Spectral Library Search.
AB  - Confident characterization of intact glycopeptides is a challenging task in mass
      spectrometry-based glycoproteomics due to microheterogeneity of glycosylation,
      complexity of glycans, and insufficient fragmentation of peptide bones. Open mass
      spectral library search is a promising computational approach to peptide
      identification, but its potential in the identification of glycopeptides has not
      been fully explored. Here we present pMatchGlyco, a new spectral library search
      tool for intact N-linked glycopeptide identification using high-energy
      collisional dissociation (HCD) tandem mass spectrometry (MS/MS) data. In
      pMatchGlyco, (1) MS/MS spectra of deglycopeptides are used to create spectral
      library, (2) MS/MS spectra of glycopeptides are matched to the spectra in library
      in an open (precursor tolerant) manner and the glycans are inferred, and (3) a
      false discovery rate is estimated for top-scored matches above a threshold. The
      efficiency and reliability of pMatchGlyco were demonstrated on a data set of
      mixture sample of six standard glycoproteins and a complex glycoprotein data set
      generated from human cancer cell line OVCAR3.

PMID- 30186850
TI  - Pharmacokinetics and Bioavailability Study of Monocrotaline in Mouse Blood by
      Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry.
AB  - Background and Aims: The present study aimed to develop a simple and sensitive
      method for quantitative determination of monocrotaline (MCT) in mouse blood
      employing ultra-performance liquid chromatography-electrospray ionization tandem
      mass spectrometry (UPLC-ESI/MS/MS) using rhynchophylline as an internal standard.
      Methods: Proteins present in the blood samples were precipitated using
      acetonitrile. MCT was separated using a 1.7-MUm ethylene bridged hybrid (BEH) C18
      column (2.1 mm * 50 mm) with a gradient elution program and a constant flow rate
      of 0.4 mL/min. The LC mobile phase consisted of 10 mmol/L ammonium acetate
      (containing 0.1% formic acid) and acetonitrile. The total elution time was 4.0
      min. The analytes were detected on a UPLC-ESI mass spectrometer in multiple
      reaction monitoring (MRM) mode and quantified. Results: The new method for the
      determination of MCT has a satisfactory linear detection range of 1-2000 ng/mL
      and excellent linearity (r = 0.9971). The lower limit of quantification (LLOQ) of
      MCT is 1.0 ng/mL. Intra- and interassay precisions of MCT were <=13% with an
      accuracy from 96.2% to 106.6%. The average recovery of the new method was >75.0%,
      and matrix effects were between 89.0% and 94.3%. Based on the pharmacokinetics
      data, the bioavailability of MCT in mice was 88.3% after oral administration.
      Conclusions: The results suggest that the newly standardized method for
      quantitative determination of MCT in whole blood is fast, reliable, specific,
      sensitive, and suitable for pharmacokinetic studies of MCT after intravenous or
      intragastric administration.

PMID- 30186851
TI  - The Effect of Intraradicular Multiple Fiber and Cast Posts on the Fracture
      Resistance of Endodontically Treated Teeth with Wide Root Canals.
AB  - Introduction: The endodontically treated teeth (ETT) with thin remaining
      radicular dentin thickness are predisposed to fracture; hence it requires the
      diligent selection and the execution of endodontic post treatment. The objective
      of the study was to evaluate the reinforcing effect of both multiple fiber
      reinforced composite (FRC) and Ni-Cr cast metal posts at anterior and posterior
      regions. Material and Methods: Forty recently extracted root canal treated canine
      and single rooted premolar teeth were used for the study. They were randomly
      divided into four groups (n=10) as: Group 1, single FRC post; Group 2, multiple
      FRC posts; Group 3, single Ni-Cr metal post, Group 4, multiple Ni-Cr posts. The
      posts were cemented with self-adhesive resin cement and subsequently restored
      with full veneer metal crown. The compressive static load at 1300 for canine and
      450 for premolar was applied with the cross-head speed of 0.5mm/minute until the
      fracture. The obtained data was analyzed using the Kruskal-Wallis and Pairwise
      comparison tests with SPSS. Results: The results indicate that multiple FRC post
      restored canine had the maximum fracture load (1843.80+/-7.13 N), followed by
      cast multiple posts (1648.99+/-26.84 N), single fiber post (1623+/-40.31 N), and
      cast metal single post (1493+/-27.33 N). A similar trend was observed in premolar
      with higher max fracture load with multiple FRC posts at 1920.86+/-20.61 N and
      multiple cast metal posts at 1735.43+/-6.05 N. Conclusion: The restoration of ETT
      with larger canals by multiple FRC and metal posts provides substantially higher
      fracture resistance in comparison to wider single post.

PMID- 30186852
TI  - Relationship between Serum Osteocalcin and Carotid Atherosclerosis in Middle-Aged
      Men in China: A Cross-Sectional Study.
AB  - Background and Purpose: Numerous investigations found that there exists a close
      relationship between serum osteocalcin and incurrence of atherosclerosis, but
      studies investigating the effect of serum osteocalcin on carotid atherosclerosis
      are very limited. Our study is aimed at investigating the role of osteocalcin in
      carotid atherosclerosis in middle-aged men in China. Methods: A total of 335 male
      middle-aged participants (40-60, 52.4 +/- 3.87 years averagely) were enrolled
      from the institute. The carotid intima-media thicknesses (CIMT) of each subject
      were measured. All subjects were included either in the carotid atherosclerosis
      (AS) group or the control group according to the CAS diagnosis criteria. Serum
      osteocalcin and other markers of each patient were assessed following standard
      laboratory tests protocol. Results: 135 subjects were included in AS group, and
      199 subjects were included in control group. The average osteocalcin level in AS
      group was 18.71 +/- 6.20 ng/ml and was significantly different from that in
      control group, which was 20.38 +/- 7.19 ng/ml (p=0.039). Logistic regression
      analysis revealed that OCN (standardized beta=-0.024, p=0.013) and FINS
      (standardized beta=-0.065, p=0.010) were independently and inversely associated
      with the carotid atherosclerosis, while FPG (standardized beta=0.538, p=0.006)
      was independently and positively associated with the carotid atherosclerosis.
      Conclusion: Our study suggests that OCN is independently related to carotid
      atherosclerosis in middle-aged male individuals.

PMID- 30186853
TI  - MiR-29a Inhibits Glioma Tumorigenesis through a Negative Feedback Loop of
      TRAF4/Akt Signaling.
AB  - Background: MiR-29a is known as a repressor of human cancer. However, its
      relevance in glioma proliferation and invasion remains largely unknown. In this
      study, we aimed to investigate the function and mechanism of miR-29a in glioma
      tumorigenesis. Methods: The expression of miR-29a was determined by using qRT
      PCR. CCK-8, wound healing, and transwell invasion assays were carried out to
      analyze the effects of miR-29a in glioblastoma cells. qRT-PCR, luciferase
      reporter, and western blot experiments were done to validate the targeting of
      TRAF4/Akt pathway by miR-29a. The expression correlation between levels of TRAF4
      and miR-29a was analyzed. Regulation of miR-29a expression by enhanced/reduced
      TRAF4/Akt expression was finally confirmed by qRT-PCR. Results: MiR-29a was
      decreased in the glioma tissues, especially in those at higher grades. Following
      its mimic transfection, we validated that miR-29a inhibited cell proliferation,
      migration, and invasion. Consistently, miR-29a inhibition induced the opposite
      effects on cell proliferation, migration, and invasion. We confirmed TRAF4 as a
      direct target of miR-29a, which might mediate the Akt pathway activation. We
      showed a significantly negative expression correlation between TRAF4 and miR-29a
      in normal and glioma tissues. Finally we observed an upregulation of miR-29a in
      TRAF4/Akt activated cells. Conclusion: MiR-29a is critical tumor suppressor for
      glioma tumorigenesis by forming a negative feedback loop of TRAF4/Akt signaling
      and represents a potent therapeutic candidate for treating gliomas.

PMID- 30186855
TI  - Aberrantly Expressed Genes and miRNAs in Slow Transit Constipation Based on RNA
      Seq Analysis.
AB  - Background: This study aims to identify the key genes and miRNAs in slow transit
      constipation (STC). Methods: MRNA and miRNA expression profiling were obtained.
      Differentially expressed genes (DEGs) and miRNAs were identified followed by the
      regulatory network construction. Functional annotation analysis and protein
      protein interaction (PPI) network were conducted. The electronic validation was
      performed. Results: Hsa-miR-2116-3p, hsa-miR-3622a-5p, hsa-miR-424-5p, and hsa
      miR-1273-3p covered most DEGs. HLA-DRB1, HLA-DRB5, C3, and ICAM were
      significantly involved in staphylococcus aureus infection. The PPI network
      generated several hub proteins including ZBTB16, FBN1, CCNF, and CDK1. Electronic
      validation of HLA-DRB1, PTGDR, MKI67, BIRC5, CCNF, and CDK1 was consistent with
      the RNA-sequencing analysis. Conclusion: Our study might be helpful in
      understanding the pathology of STC at the molecular level.

PMID- 30186854
TI  - Electric Pulses Can Influence Galvanotaxis of Dictyostelium discoideum.
AB  - Galvanotaxis, or electrotaxis, plays an essential role in wound healing,
      embryogenesis, and nerve regeneration. Up until now great efforts have been made
      to identify the underlying mechanism related to galvanotaxis in various cells
      under direct current electric field (DCEF) in laboratory studies. However,
      abundant clinical research shows that non-DCEFs including monopolar or bipolar
      electric field may also contribute to wound healing and regeneration, although
      the mechanism remains elusive. Here, we designed a novel electric stimulator and
      applied DCEF, pulsed DCEF (pDCEF), and bipolar pulse electric field (bpEF) to the
      cells of Dictyostelium discoideum. The cells had better directional performance
      under asymmetric 90% duty cycle pDCEF and 80% duty cycle bpEF compared to DCEF,
      with 10 Hz frequency electric fields eliciting a better cell response than 5 Hz.
      Interestingly, electrically neutral 50% duty cycle bpEF triggered the highest
      migration speed, albeit in random directions. The results suggest that electric
      pulses are vital to galvanotaxis and non-DCEF is promising in both basic and
      clinical researches.

PMID- 30186856
TI  - Cost Saving Potential of an Early Detection of Atrial Fibrillation in Patients
      after ICD Implantation.
AB  - Atrial fibrillation (AF) is a relevant comorbidity in recipients of implantable
      cardioverter-defibrillators (ICD). Latest generation single-chamber ICD allow the
      additional sensing of atrial tachyarrhythmias and, therefore, contribute to the
      early detection and treatment of AF, potentially preventing AF-related stroke.
      The present study aimed to measure the impact on patient-related costs of this
      new ICD compared to conventional ICD. A Markov model was developed to simulate
      the long-term incidence of stroke in patients treated with a single-chamber ICD
      with or without atrial sensing capabilities. The median annual cost per patient
      and its difference, the number of strokes avoided, and the cost per stroke
      avoided were estimated. During a 9-year horizon, the costs for the ICD and stroke
      treatment were ?570 per patient-year for an ICD with atrial sensing capabilities
      and ?491 per patient-year for a conventional ICD. Per 1,000 patients, 4.6 strokes
      per year are assumed to be avoided by the new device. Higher CHA2DS2-VASc scores
      are associated with higher numbers of avoided strokes and larger potential for
      cost savings. Apart from clinical advantages, the use of ICD with atrial sensing
      capabilities may reduce the incidence of stroke and, in high-risk patients, may
      also contribute to reduce overall health care costs.

PMID- 30186857
TI  - Histogram Analysis of Perfusion Parameters from Dynamic Contrast-Enhanced MR
      Imaging with Tumor Characteristics and Therapeutic Response in Locally Advanced
      Rectal Cancer.
AB  - Purpose: To explore the role of histogram analysis of perfusion parameters from
      dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) based on entire
      tumor volume in discriminating tumor characteristics and predicting therapeutic
      response in rectal cancer. Materials and Methods: Thirty-seven DCE-MRIs of
      locally advanced rectal cancer patients who received chemoradiation therapy (CRT)
      before surgery were analyzed by pharmacokinetic model for quantification and
      histogram analysis of perfusion parameters. The results were correlated with
      tumor characteristics including EGFR expression, KRAS mutation, and CRT response
      based on the pathologic tumor regression grade (TRG). Results: The area under the
      contrast agent concentration-time curve (AUC) skewness was significantly lower in
      patients with node metastasis. The vp histogram parameters were significantly
      higher in group with perineural invasion (PNI). The receiver operating
      characteristics (ROC) curve analyses showed that mode vp revealed the best
      diagnostic performance of PNI. The values of Ktrans and kep were significantly
      higher in the group with KRAS mutation. ROC curve analyses showed that mean and
      mode Ktrans demonstrated excellent diagnostic performance of KRAS mutation. DCE
      MRI parameters did not demonstrate statistical significance in correlating with
      TRG. Conclusion: These preliminary results suggest that a larger proportion of
      higher AUC skewness was present in LN metastasis group and a higher vp histogram
      value was present in rectal cancer with PNI. In addition, Ktrans and kep
      histogram parameters showed difference according to the KRAS mutation,
      demonstrating the utility of the histogram of perfusion parameters derived from
      DCE-MRI as potential imaging biomarkers of tumor characteristics and genetic
      features.

PMID- 30186858
TI  - Nanosecond Electric Pulses Induce Early and Late Phases of DNA Damage and Cell
      Death in Cisplatin-Resistant Human Ovarian Cancer Cells.
AB  - Chemoresistance is a challenge for management of ovarian cancer, and therefore
      the response of resistant cells to nanosecond electric pulses (nsEP) was
      explored. Human ovarian cancer cell line COC1 and the cisplatin-resistant subline
      COC1/DDP were subjected to nsEP (32 ns, 10 kV/cm, 10 Hz pulse repletion
      frequency, and 10 min exposure duration), and then the cellular responses were
      followed. The percentages of dead cells and of comet-formed cells in the alkaline
      assay displayed two peak levels (i.e., 2 and 8 h after nsEP exposure), with the
      highest value noted at 8 h; the percentage of comet-formed cells in the neutral
      assay was increased at 8 h; the apoptotic percentage was increased at 8 h, with
      collapse of the mitochondrial membrane potential and the activation of caspase-3
      and caspase-9. The comet assay demonstrated DNA single-strand break at 2 h and
      double-strand break at 8 h. nsEP resulted in lower cytotoxicity in COC1/DDP cells
      compared with COC1 cells. These findings indicated that nsEP induced early and
      late phases of DNA damage and cell death, and these two types of cell death may
      have distinct applications to treatments of chemoresistant ovarian cancers.

PMID- 30186860
TI  - Rectal Cancer: Redox State of Venous Blood and Tissues of Blood Vessels from
      Electron Paramagnetic Resonance and Its Correlation with the Five-Year Survival.
AB  - A role of pro- and antioxidants for reducing rectal cancer (RC) incidence in
      operative, preoperative, and postoperative treatments is still disputable and
      controversial. The redox state of venous blood and tissues of blood vessels of 60
      patients with RC (T2-4N0-2M0G2) and 20 donors is studied by means of the
      conventional and spin-trapping electron paramagnetic resonance (EPR). The
      intensity of the signals from ceruloplasmin (CP), transferrin (TF), and labile
      iron pool (LIP) at temperature T = 77 K as well as superoxide generation rate and
      nitric oxide (NO) levels at T = 300 K is measured. The reduced CP and TF activity
      and decreased NO levels increased LIP levels and superoxide-generating rates are
      detected in blood species. Correlation analysis for the five-year survival rate
      as a function of the extracted values is done. The results show that the
      intensities of the corresponding EPR signals from the "native" and "trapped"
      paramagnetic centers can be potentially used for the understanding of the
      molecular mechanisms underlying the RC progression and treatment.

PMID- 30186859
TI  - Rab GTPases in Osteoclastic Endomembrane Systems.
AB  - Osteoclasts (OCs) are bone-resorbing cells that maintain bone homeostasis. OC
      differentiation, survival, and activity are regulated by numerous small GTPases,
      including those of the Rab family, which are involved in plasma membrane delivery
      and lysosomal and autophagic degradation pathways. In resorbing OCs, polarized
      vesicular trafficking pathways also result in formation of the ruffled membrane,
      the resorbing organelle, and in transcytosis.

PMID- 30186861
TI  - Reperfusion Activates AP-1 and Heat Shock Response in Donor Kidney Parenchyma
      after Warm Ischemia.
AB  - Utilization of kidneys from extended criteria donors leads to an increase in
      average warm ischemia time (WIT), which is associated with larger degrees of
      ischemia-reperfusion injury (IRI). Kidney resuscitation by extracorporeal
      perfusion in situ allows up to 60 minutes of asystole after the circulatory
      death. Molecular studies of kidney grafts from human donors with critically
      expanded WIT are warranted. Transcriptomes of two human kidneys from two
      different donors were profiled after 35-45 minutes of WIT and after 120 minutes
      of normothermic perfusion and compared. Baseline gene expression patterns in
      ischemic grafts display substantial intrinsic differences. IRI does not lead to
      substantial change in overall transcription landscape but activates a highly
      connected protein network with hubs centered on Jun/Fos/ATF transcription factors
      and HSP1A/HSPA5 heat shock proteins. This response is regulated by positive
      feedback. IRI networks are enriched in soluble proteins and biofluids assayable
      substances, thus, indicating feasibility of the longitudinal, minimally invasive
      assessment in vivo. Mapping of IRI related molecules in ischemic and reperfused
      kidneys provides a rationale for possible organ conditioning during machine
      assisted ex vivo normothermic perfusion. A study of natural diversity of the
      transcriptional landscapes in presumably normal, transplantation-suitable human
      organs is warranted.

PMID- 30186862
TI  - Neuroprotective Activity of Sitagliptin via Reduction of Neuroinflammation beyond
      the Incretin Effect: Focus on Alzheimer's Disease.
AB  - Sitagliptin is a member of a class of drugs that inhibit dipeptidyl peptidase
      (DPP-4). It increases the levels of the active form of incretins such as GLP-1
      (glucagon-like peptide-1) or GIP (gastric inhibitory polypeptide) and by their
      means positively affects glucose metabolism. It is successfully applied in the
      treatment of diabetes mellitus type 2. The most recent scientific reports suggest
      beneficial effect of sitagliptin on diseases in which neuron damage occurs.
      Result of experimental studies may indicate a reducing influence of sitagliptin
      on inflammatory response within encephalon area. Sitagliptin decreased the levels
      of proinflammatory factors: TNF-alpha (tumor necrosis factor-alpha), IL-6
      (interleukin-6), IL-17 (interleukin-17), and CD-163 (cluster of differentiation
      163), and contributed to an increase in levels of anti-inflammatory factors: IL
      10 (interleukin-10) and TGF-beta (transforming growth factor beta). Moreover,
      sitagliptin demonstrated antioxidative and antiapoptotic properties by modifying
      glutamate and glutathione levels within the region of hippocampus in mice. It has
      been observed that sitagliptin decreases accumulation of beta-amyloid within
      encephalon structures in experimental models of Alzheimer's dementia. This effect
      may be connected with SDF-1alpha (stromal cell-derived factor 1alpha)
      concentration. Administration of sitagliptin caused a significant improvement in
      MMSE (Mini-Mental State Examination) tests used for assessment of dementias. The
      paper presents potential mechanisms of sitagliptin activity in conditions
      connected with neuroinflammation with special emphasis on Alzheimer's disease.

PMID- 30186864
TI  - Maxillary Sinus Floor Augmentation to Enable One-Stage Implant Placement by Using
      Bovine Bone Substitute and Platelet-Rich Fibrin.
AB  - Nowadays it is possible to perform an optimal implant placement and to achieve a
      good long-term prognosis for an implant-borne prosthesis in the grafted posterior
      maxilla. This study evaluates the efficiency of one-stage piezosurgery by using
      as graft material a combination of particulate bovine bone substitutes with
      platelet-rich fibrin to achieve sinus lift. We included in this study 14 cases of
      one-stage sinus lift surgeries during which we placed 30 standard implants. The
      mean vertical bone height gain was 10.12 mm six months after surgery, and the
      mean postoperative follow-up time was 43.79 months. There were no major
      complications during or after surgery, and all implants are in use. Therefore, it
      can be concluded that one-stage sinus piezosurgery using particulate bovine bone
      substitutes and platelet-rich fibrin can be applied as a predictable and
      effective technique in the treatment of the posterior edentulous maxilla ensuring
      4-5 mm vertical bone height.

PMID- 30186863
TI  - Small-Molecule Modulation of Lipid-Dependent Cellular Processes against Cancer:
      Fats on the Gunpoint.
AB  - Lipid cell membrane composed of various distinct lipids and proteins act as a
      platform to assemble various signaling complexes regulating innumerous cellular
      processes which are strongly downregulated or altered in cancer cells emphasizing
      the still-underestimated critical function of lipid biomolecules in cancer
      initiation and progression. In this review, we outline the current understanding
      of how membrane lipids act as signaling hot spots by generating distinct membrane
      microdomains called rafts to initiate various cellular processes and their
      modulation in cancer phenotypes. We elucidate tangible drug targets and pathways
      all amenable to small-molecule perturbation. Ranging from targeting membrane
      rafts organization/reorganization to rewiring lipid metabolism and lipid sorting
      in cancer, the work summarized here represents critical intervention points being
      attempted for lipid-based anticancer therapy and future directions.

PMID- 30186865
TI  - Immediate Loading of Implant-Supported Single Crowns after Conventional and
      Ultrasonic Implant Site Preparation: A Multicenter Randomized Controlled Clinical
      Trial.
AB  - Aim: To compare implant survival rate and marginal bone loss (MBL) of immediately
      loaded single implants inserted by using ultrasonic implant site preparation
      (UISP) (test) and conventional rotary instrumentation (control). Methods: Two
      single implants were inserted for each patient: after randomization, test site
      was prepared by using an ultrasonic device (Piezosurgery Touch, Mectron, Italy)
      and control site was prepared by using the drills of the selected implant system
      (Premium AZT, Sweden & Martina, Italy), until reaching a final diameter of 3 mm
      in both groups. Identical implants (3.8x11.5 mm) were inserted in all sites at
      crestal level. Impressions were taken and screwed resin single crowns with
      platform-switched provisional abutments were delivered with 48 hours. Periapical
      radiographs were taken at provisional crown insertion (T0), 6 months (T1) and one
      year (T2) after prosthetic loading to measure MBL. All data were tested for
      normality and subsequently analyzed by paired samples t-test and forward multiple
      linear regression. Results: Forty-eight patients were treated in six centers with
      the insertion of ninety-six implants (48 test; 48 control). Four implants in four
      patients failed within the first six months of healing (two in test group; two in
      control group; no difference between groups). Forty patients (age 60.1+/-10.7
      years; 22 female, 18 male) were included in the final analysis. Mean MBL after
      six months of loading was 1.39+/-1.03 mm in the test group and 1.42+/-1.16 mm in
      the control group (p>0.05) and after one year was 1.92+/-1.14 mm and 2.14+/-1.55
      mm in test and control, respectively (p>0.05). Conclusions: No differences in
      survival rate and MBL were demonstrated between UISP and conventional site
      preparation with rotary instruments in immediately loaded dental implants: UISP,
      with its characteristics of enhanced surgical control and safety in proximity of
      delicate structures, may be used as a reliable alternative to the traditional
      drilling systems.

PMID- 30186866
TI  - Levocetirizine Pretreatment Mitigates Lipopolysaccharide-Induced Lung
      Inflammation in Rats.
AB  - This research was conducted to investigate possible protective influences of
      levocetirizine, a nonsedating H1 antihistamine, against lipopolysaccharide (LPS)
      induced lung injury in rats. Male Sprague Dawley rats received either
      levocetirizine (1 mg/kg/day, orally) or the vehicle of the drug (2 ml/kg/day,
      orally) for 1 week before a single IP injection of LPS (7.5 mg/kg). A group of
      normal rats served as control. The experiments were terminated 18 h after the LPS
      challenge. Serum C-reactive protein levels were determined. Moreover, total cell
      count, lactate dehydrogenase (LDH) activity, protein levels, and total NOx were
      evaluated in bronchoalveolar lavage fluid (BALF). Pulmonary edema was evaluated
      as the wet/dry lung weight ratio. Lung tissue homogenate was assessed for
      antioxidant/pro-oxidant status. BALF and lung tissue levels of tumor necrosis
      factor-alpha (TNF-alpha) were assessed. Lungs were examined for histological
      alterations. LPS-mediated lung injury was manifested by pulmonary edema,
      leukocyte infiltration, oxidative stress, and inflammation. Levocetirizine
      attenuated lung edema and mitigated the increases in BALF protein levels, LDH
      activity, and lung leukocyte recruitment in LPS-challenged rats. Additionally,
      TNF-alpha protein levels in BALF and lung tissue were diminished by
      levocetirizine administration. Levocetirizine also exhibited a potent antioxidant
      activity as indicated by a decrease in lung tissue levels of malondialdehyde and
      an enhancement of superoxide dismutase activity. Histological examination of lung
      tissues confirmed the beneficial effect of levocetirizine against LPS-induced
      histopathological alterations. In conclusion, levocetirizine may offer protection
      against lung tissue damage and inflammation in LPS-challenged rats.

PMID- 30186867
TI  - Cone-Beam Computed Tomographic Evaluation of Root Canal Morphology of Maxillary
      Premolars in a Saudi Population.
AB  - Objective: The aim of the study was to investigate the root canal morphology of
      maxillary first and second premolars in a Saudi population using Cone-Beam
      Computed Tomography (CBCT). Methods: This retrospective cross-sectional study
      assessed CBCT images of 707 Saudi patients. The number of roots and canal
      configuration were identified based on Vertucci's classification. Fisher's exact
      Chi-square tests were performed to analyze the association between sex and number
      of roots and sex and root canal configuration. Results: Most teeth had two roots
      in maxillary first premolars (75.1%) and one root in maxillary second premolars
      (85.2%). Type IV was the most prevalent canal configuration in maxillary first
      premolars (69.1%), while Type I was the most in maxillary second premolars
      (49.4%). All types of canal configurations were observed in maxillary premolars
      except Type VII for the maxillary second premolar. Chi-square tests showed no
      significant association between gender and number of roots and sex and root canal
      configuration in both maxillary first and second premolars although higher number
      of roots was seen in men (P > 0.05). Conclusion: Most maxillary first premolars
      had two roots with Type IV being the most predominant canal configuration, while
      a single root with Type I canal configuration was the most frequently observed
      morphology in maxillary second premolars. In maxillary first premolars, 21.3% had
      one canal apically, 75.4% had two canals apically, and 3.3% had three canals
      apically. In maxillary second premolars, 80.2% had one canal apically, 18.9% had
      two canals apically, and 0.9% had three canals apically.

PMID- 30186868
TI  - Siji Antiviral Mixture Protects against CA16 Induced Brain Injury through
      Inhibiting PERK/STAT3/NF-kappaB Pathway.
AB  - Coxsackievirus 16 (CA16) causes hand, foot, and mouth disease (HFMD) in young
      children and infants, and it can lead to fatal neurological complications. This
      study investigated antiviral effects of Siji Antiviral Mixture (SAM) on CA16 in
      neonatal mice and the protective effects of SAM on CA16 induced brain injuries.
      Neonatal BALB/c mice and SH-SY5Y cells were used and injected with CA16 stains to
      study the efficacy. ELISA and Western blotting were used to measure the cytokines
      levels and proteins expression. Genes transduction was also used to verify
      interaction mechanism. As the results shown, SAM could reduce the clinical scores
      at the beginning and delay disease development in vivo. Treatment with SAM
      decreased the levels of LDH, CK-MB, caspase 3 and Bax, ER stress, and
      inflammatory reaction induced by CA16 infection. Further siRNA transfection
      results showed that CA16 induced ER stress and inflammatory reaction through
      PERK/STAT3/NF-kappaB signaling and the protective effects of SAM might be through
      inhibiting PERK/STAT3/NF-kappaB signaling. HPLC analysis showed fingerprint
      profiles of SAM had 42 chromatographic peaks. Collectively, our study highlighted
      distinct roles of SAM in inhibiting CA16 infection and brain injury. The
      molecular mechanism of SAM might be through inhibiting PERK/STAT3/NF-kappaB
      signaling.

PMID- 30186869
TI  - Lean Body Weight-Tailored Iodinated Contrast Injection in Obese Patient: Boer
      versus James Formula.
AB  - Purpose: To prospectively compare the performance of James and Boer formula in
      contrast media (CM) administration, in terms of image quality and parenchymal
      enhancement in obese patients undergoing CT of the abdomen. Materials and
      Methods: Fifty-five patients with a body mass index (BMI) greater than 35 kg/m2
      were prospectively included in the study. All patients underwent 64-row CT
      examination and were randomly divided in two groups: 26 patients in Group A and
      29 patients in Group B. The amount of injected CM was computed according to the
      patient's lean body weight (LBW), estimated using either Boer formula (Group A)
      or James formula (Group B). Patient's characteristics, CM volume, contrast-to
      noise ratio (CNR) of liver, aorta and portal vein, and liver contrast enhancement
      index (CEI) were compared between the two groups. For subjective image analysis
      readers were asked to rate the enhancement of liver, kidneys, and pancreas based
      on a 5-point Likert scale. Results: Liver CNR, aortic CNR, and portal vein CNR
      showed no significant difference between Group A and Group B (all P >= 0.177).
      Group A provided significantly higher CEI compared to Group B (P = 0.007). Group
      A and Group B returned comparable overall subjective enhancement values (3.54 and
      vs 3.20, all P >= 0.199). Conclusions: Boer formula should be the method of
      choice for LBW estimation in obese patients, leading to an accurate CM amount
      calculation and an optimal liver contrast enhancement in CT.

PMID- 30186870
TI  - Effect of Load Cycling on the Fracture Strength/Mode of Teeth Restored with FRC
      Posts or a FRC Liner and a Resin Composite.
AB  - The aim of the study was to comparatively evaluate the fracture strength and mode
      of root canal treated teeth restored with resin composites with and without
      posts. The lingual cusps of root canal treated first upper premolars (n =
      10/group) were removed down to cervical enamel and restored with the following:
      group A: glass-fiber post (Glassix) followed by a particulate-filled composite
      resin (PFC, G-aenial posterior, 3 * 2 mm layers); group B: glass-fiber reinforced
      composite bulk fill liner (EverX posterior, 4 mm layer) with the PFC (2 mm
      layer). Specimens were immersed in H2O (1 w/37 degrees C), then subjected to load
      cycling (50 N/0.2 Hz/200k cycles), and fractured under compressive loading.
      Failure mode was characterized by stereomicroscopy. Statistical analysis was
      performed by Mann-Whitney (load) and Chi-square (mode) at a = 0.05. No
      statistically significant differences (p = 0.273) were found in fracture load
      between median values of groups A (860 N) and B (1059 N). In group A, 60% of the
      specimens demonstrated catastrophic root fractures and 40% mixed crown fractures
      (tooth cusp and restoration), whereas in group B, no root fractures were found,
      and the failure modes were equally distributed between mixed fractures as above
      and fracture of the buccal cusp. These differences were statistically significant
      (p = 0.004). The combination of the glass-FRC bulk fill liner with the PFC
      diminished the catastrophic root fractures induced by FRC posts, at a similar or
      higher fracture load.

PMID- 30186871
TI  - Developmental Programming of Capuchin Monkey Adrenal Dysfunction by Gestational
      Chronodisruption.
AB  - In the capuchin monkey (Cebus apella), a new-world nonhuman primate, maternal
      exposure to constant light during last third of gestation induces precocious
      maturation of the fetal adrenal and increased plasma cortisol in the newborn.
      Here, we further explored the effects of this challenge on the developmental
      programming of adrenal function in newborn and infant capuchin monkeys. We
      measured (i) plasma dehydroepiandrosterone sulphate (DHAS) and cortisol response
      to ACTH in infants with suppressed endogenous ACTH, (ii) plasma DHAS and cortisol
      response to ACTH in vitro, and (iii) adrenal weight and expression level of key
      factors in steroid synthesis (StAR and 3beta-HSD). In one-month-old infants from
      mothers subjected to constant light, plasma levels of cortisol and cortisol
      response to ACTH were twofold higher, whereas plasma levels of DHAS and DHAS
      response to ACTH were markedly reduced, compared to control conditions. At 10
      months of age, DHAS levels were still lower but closer to control animals,
      whereas cortisol response to ACTH was similar in both experimental groups. A
      compensatory response was detected at the adrenal level, consisting of a 30%
      increase in adrenal weight and about 50% reduction of both StAR and 3beta-HSD
      mRNA and protein expression and the magnitude of DHAS and cortisol response to
      ACTH in vitro. Hence, at birth and at 10 months of age, there were differential
      effects in DHAS, cortisol production, and their response to ACTH. However, by 10
      months of age, these subsided, leading to a normal cortisol response to ACTH.
      These compensatory mechanisms may help to overcome the adrenal alterations
      induced during pregnancy to restore normal cortisol concentrations in the growing
      infant.

PMID- 30186872
TI  - Integration of Gene Expression Profile Data to Screen and Verify Hub Genes
      Involved in Osteoarthritis.
AB  - Osteoarthritis (OA) is one of the most common diseases worldwide, but the
      pathogenic genes and pathways are largely unclear. The aim of this study was to
      screen and verify hub genes involved in OA and explore potential molecular
      mechanisms. The expression profiles of GSE12021 and GSE55235 were downloaded from
      the Gene Expression Omnibus (GEO) database, which contained 39 samples, including
      20 osteoarthritis synovial membranes and 19 matched normal synovial membranes.
      The raw data were integrated to obtain differentially expressed genes (DEGs) and
      were deeply analyzed by bioinformatics methods. The Gene Ontology (GO) and
      pathway enrichment of DEGs were performed by DAVID and Kyoto Encyclopedia of
      Genes and Genomes (KEGG) online analyses, respectively. The protein-protein
      interaction (PPI) networks of the DEGs were constructed based on data from the
      STRING database. The top 10 hub genes VEGFA, IL6, JUN, IL1beta, MYC, IL4, PTGS2,
      ATF3, EGR1, and DUSP1 were identified from the PPI network. Module analysis
      revealed that OA was associated with significant pathways including TNF signaling
      pathway, cytokine-cytokine receptor interaction, and osteoclast differentiation.
      The qRT-PCR result showed that the expression level of IL6, VEGFA, JUN, IL-1beta,
      and ATF3 was significantly increased in OA samples (p < 0.05), and these
      candidate genes could be used as potential diagnostic biomarkers and therapeutic
      targets of OA.

PMID- 30186873
TI  - Steam Sterilization of Equine Bone Block: Morphological and Collagen Analysis.
AB  - Introduction: The use of equine bone blocks is widely reported for bone
      augmentation techniques. The block must be shaped according to the form of the
      defect that should be regenerated. The shaping could be performed by hand before
      or during the surgery, in a sterile ambient, or using a CNC milling machine that
      could not be sterile. The aim of our study was to evaluate if a steam
      sterilization could provide a medical grade sterilization of the blocks and to
      evaluate if bone microstructure and collagen structures change after different
      steam sterilization protocols provided by mainstream autoclave. Materials and
      Method: Two blocks of equine bone were divided into 16 samples. 1 sample was used
      as control and not submitted to any treatment. 15 samples were infected with a
      Streptococcus faecalis bacterial culture. The samples were singularly packed,
      randomly divided into 3 groups, and submitted to autoclave sterilization on the
      same device. The groups were submitted to a sterilization cycle (Gr. A: 121
      degrees C, 1,16 bar for 20'; Gr. B:134 degrees C, 2,16 bar for 4'; Gr. C: 134
      degrees C, 2,16 bar for 3.30 min.). 2 samples for each group were evaluated for
      the sterility. 3 samples for each group were observed at SEM to notice the macro-
      and microstructure modification and to confocal microscope to observe the
      collagen. Results: All samples were sterile. The SEM evaluation showed, in all
      groups, a preserved morphological structure. Confocal microscope evaluation shows
      that the collagen structure appears to be more uniform and preserved in group C.
      Conclusion: Data show that autoclave steam sterilization could be reliable to
      obtain sterilization of equine bone blocks.

PMID- 30186874
TI  - Prevalence and Risk Factors for Glucose Intolerance among Saudi Women with
      Gestational Diabetes.
AB  - Objectives: The objective of this study was to determine the incidence and risk
      factors of glucose intolerance one year after delivery in women with gestational
      diabetes (GDM). Methods: All women who had GDM and completed one year since
      delivery at King Khalid University Hospital were contacted to participate in the
      study. Based on to the American Diabetes Association criteria and the results of
      fasting blood glucose (FPG) and HbA1c, participants were classified into three
      groups: diabetic, impaired glucose tolerance (IGT), and normal. The incidence of
      diabetes and IGT was calculated. Clinical, biochemical, and sociodemographic
      predictors of glucose intolerance were compared between the three groups. Odds
      ratio (OR) for risk factors with P value less than 0.05 was calculated. Results:
      From a total 316 eligible women, 133 fulfilled the inclusion criteria and agreed
      to participate in the study. From the study participants, 58 (44%) women were
      normoglycemic, 60 (45%) women had IGT, and 15 (11%) women were diabetic. The odds
      of developing IGT or diabetes increased to nearly fourfold when women needed
      insulin for the control of GDM during pregnancy (OR 3.8, 95% CI 0.81-18.3, P =
      0.08) and to nearly one-and-a-half-fold when they have positive family history of
      T2DM (OR 1.2, 95% CI 0.74-2.09, P = 0.40). Nevertheless, none of the odds ratios
      was statistically significant. Conclusion: The incidence of postpartum
      hyperglycemia (diabetes and IGT) is very high in Saudi women with GDM. Family
      history of diabetes and insulin treatment of GDM may be predictors of postpartum
      hyperglycemia.

PMID- 30186875
TI  - Enhancement of Adiponectin Ameliorates Nonalcoholic Fatty Liver Disease via
      Inhibition of FoxO1 in Type I Diabetic Rats.
AB  - Nonalcoholic fatty liver disease (NAFLD) is a common liver disease which has been
      previously shown to be associated with type 2 diabetes mellitus (T2DM). Recent
      research has indicated that type 1 diabetes mellitus (T1DM) is also involved in
      the development of nonalcoholic fatty liver disease, whereas the underlying
      mechanisms are largely unknown. Forkhead box O1 (FoxO1) and adiponectin (APN)
      have been proposed to play an important role in the processes in NAFLD in T1DM.
      We herein investigated the effects of FoxO1 and APN on the development of NAFLD
      and the underlying mechanism in streptozotocin-induced T1DM. Serum liver enzymes
      AST, ALT, and triglyceride (TG) were determined by commercially available kits.
      Blood glucose levels were measured by the OneTouch Ultra glucose meter. Relevant
      protein expression was tested by Western blot analysis. Results showed that serum
      AST, ALT, and TG were all significantly increased in T1DM rats, which was
      ameliorated by application of APN or selective inhibition of FoxO1 with
      AS1842856. Moreover, APN and AS1842856 both decreased the expression of liver
      nuclear FoxO1 which was significantly increased in diabetic rats. However, the
      inhibition of FoxO1 did not alter the expression of APN and its receptors. We
      also found that Akt1 expression was significantly declined in diabetic rat which
      was restored by APN and moderately and significantly increased by FoxO1
      inhibition. It is concluded that APN ameliorates NAFLD via inhibition of FoxO1
      through Akt1/FoxO1 signaling pathway.

PMID- 30186876
TI  - Involvement of RBP4 in Diabetic Atherosclerosis and the Role of Vitamin D
      Intervention.
AB  - The purposes of this study were to evaluate the expression of retinol-binding
      protein 4 (RBP4) in diabetic rats with atherosclerosis and to investigate the
      role of vitamin D intervention. Male Wistar rats were randomly divided into 4
      groups, including the control group (NC), the diabetic rats (DM1), the untreated
      diabetic atherosclerosis rats (DM2), and the vitamin D-treated diabetic
      atherosclerosis rats (DM3). The levels of serum and adipose RBP4, fasting insulin
      (FINS), fasting plasma glucose (FPG), total cholesterol (TC), high-density
      lipoprotein cholesterol (HDL-c), triglycerides (TG), low-density lipoprotein
      cholesterol (LDL-c), 25-hydroxyvitamin D [25(OH)D], C-reactive protein (CRP), and
      systolic blood pressure (SBP) were measured. Homeostasis model assessment of
      insulin resistance (HOMA-IR), homeostasis model assessment beta-cell function
      index (HOMA-beta), and atherogenic indexes (AI) were calculated. Compared with
      group NC, the levels of RBP4, TG, LDL-c, FPG, FINS, CRP, AI1, AI2, SBP, and HOMA
      IR increased, while the levels of HDL-c, 25(OH)D, and HOMA-beta decreased in
      groups DM1 and DM2. After 8 weeks of vitamin D supplementation in group DM3, the
      levels of 25(OH)D and HOMA-beta increased and the levels of LDL-c, TC, HOMA-IR,
      FINS, CRP, RBP4, AI1, AI2, and SBP decreased significantly when compared with
      group DM2 (P < 0.05); Pearson analysis showed that serum RBP4 was positively
      correlated with TG, FINS, HOMA-IR, SBP, CRP, and AI and negatively correlated
      with 25(OH)D. In addition, multivariable logistic regression analysis showed that
      serum RBP4, SBP, and HDL-c were predictors for the presence of diabetic
      atherosclerosis. These findings suggested that RBP4 could involve in the
      improvement of diabetic atherosclerosis; vitamin D had the ability to decrease
      the level of RBP4 and eventually played an important role in preventing
      atherosclerosis in diabetes.

PMID- 30186877
TI  - TERT and Akt Are Involved in the Par-4-Dependent Apoptosis of Islet beta Cells in
      Type 2 Diabetes.
AB  - Islet beta cell apoptosis plays an important role in type 2 diabetes. We
      previously reported that Par-4-mediated islet beta cell apoptosis is induced by
      high-glucose/fatty acid levels. In the present study, we show that Par-4, which
      is induced by high-glucose/fatty acid levels, interacts with and inhibits TERT in
      the cytoplasm and then translocates to the nucleus. Par-4 also inhibited Akt
      phosphorylation, leading to islet beta cell apoptosis. We inhibited Par-4 in
      islet beta cells under high-glucose/fatty acid conditions and knocked out Par-4
      in diabetic mice, which led to the up-regulation of TERT and an improvement in
      the apoptosis rate. We inhibited Akt phosphorylation in islet beta cells and
      diabetic mice, which led to aggressive apoptosis. In addition, the biological
      film interference technique revealed that Par-4 bound to TERT via its NLS and
      leucine zipper domains. Our research suggests that Par-4 activation and binding
      to TERT are key steps required for inducing the apoptosis of islet beta cells
      under high-glucose/fatty acid conditions. Inhibiting Akt phosphorylation
      aggravated apoptosis by activating Par-4 and inhibiting TERT, and Par-4
      inhibition may be an attractive target for the treatment of islet beta cell
      apoptosis.

PMID- 30186878
TI  - The Coincidence of Newly Diagnosed Type 1 Diabetes Mellitus with IgM Antibody
      Positivity to Enteroviruses and Respiratory Tract Viruses.
AB  - Objective: Viruses trigger and promote islet cell destruction and cause type 1
      diabetes mellitus (T1DM). However, the existence of a cause-and-effect
      relationship is under debate. The aim of this study is to investigate the sero
      epidemiological and molecular evidence on enteroviruses and respiratory viruses
      in patients with newly diagnosed T1DM during the cold season. Design: Forty
      children newly diagnosed with T1DM and 30 healthy children who presented to the
      clinic over the course of a year were included in the study. The IgM antibodies
      against enteroviruses and respiratory viruses were studied using the indirect
      immunofluorescence assay (IFA) test, and no CBV4-specific RNA was detected in the
      children. The onset times of T1DM were classified into fall-winter and spring
      summer seasons and separated into cold, moderate, or warm months in terms of
      temperature. Results: The percentages of viral IgM antibodies against most common
      viruses were detected in the patients as follows: influenza B (IVB) (70%),
      echovirus 7 (ECHO7) (45%), parainfluenza virus 4 (PIV4) (40%), coxsackievirus A7
      (CAV7) (27.5%), and H3N2 (22.5%). Compared with the control group, the above
      viruses had a significant association with T1DM (p <= 0.001, p <= 0.001, p =
      0.035, p = 0.003, and p = 0.023, resp.). CBV4-specific RNA was not detected in
      any serum. A total of 75% and 95% patients were diagnosed with T1DM in the fall
      winter seasons and cold-moderate months, respectively. Conclusion: Our study
      demonstrates the significant association between T1DM and the presence of IgM
      antibodies against IVB, ECHO7, PIV4, CAV7, and H3N2, and the majority of newly
      diagnosed T1DM appeared in the fall-winter season. It suggests that enteroviruses
      and respiratory viruses, in addition to seasonal variation, could play a role in
      the etiopathogenesis and clinical onset of T1DM.

PMID- 30186879
TI  - Type I/II Interferon in HIV-1-Infected Patients: Expression in Gut Mucosa and in
      Peripheral Blood Mononuclear Cells and Its Modification upon Probiotic
      Supplementation.
AB  - Expression of type I and II interferon (IFN) was evaluated in gut-associated
      lymphoid tissue (GALT) and peripheral blood mononuclear cells (PBMCs) of HIV-1
      positive patients on long-term, suppressive, antiretroviral therapy before and
      after probiotic supplementation. IFNalpha subtypes and IFNbeta were expressed at
      higher levels in GALT compared to PBMC, whereas an opposite trend of expression
      was recorded for IFNgamma. An increase of IFNalpha6, IFNalpha10, IFNalpha14,
      IFNalpha17, and IFNalpha21 and a decrease of IFNgamma were observed in both
      anatomical sites after probiotic supplementation.

PMID- 30186880
TI  - Assessing the Role of DNA Methylation-Derived Neutrophil-to-Lymphocyte Ratio in
      Rheumatoid Arthritis.
AB  - Rheumatoid arthritis (RA) is a disease of chronic systemic inflammation (SI). In
      the present study, we used four datasets to explore whether methylation-derived
      neutrophil-to-lymphocyte ratio (mdNLR) might be a marker of SI in new onset,
      untreated, and treated prevalent RA cases and/or a marker of treatment response
      to the tumour necrosis factor inhibitor (TNFi) etanercept. mdNLR was associated
      with increased odds of being a new onset RA case (OR = 2.32, 95% CI = 1.95-2.80,
      P < 2 * 10-16) and performed better in distinguishing new onset RA cases from
      controls compared to covariates: age, gender, and smoking status. In untreated
      preclinical RA cases and controls, mdNLR at baseline was associated with
      diagnosis of RA in later life after adjusting for batch (OR = 4.30, 95% CI = 1.52
      21.71, P = 0.029) although no association was observed before batch correction.
      When prevalent RA cases were treated, there was no association with mdNLR in
      samples before and after batch correction (OR = 0.34, 95% CI = 0.05-1.82, P =
      0.23), and mdNLR was not associated with treatment response to etanercept (OR =
      1.10, 95% CI = 0.75-1.68, P = 0.64). Our results indicate that SI measured by DNA
      methylation data is indicative of the recent onset of RA. Although preclinical RA
      was associated with mdNLR, there was no difference in the mean mdNLR between
      preclinical RA cases and controls. mdNLR was not associated with RA case status
      if treatment for RA has commenced, and it is not associated with treatment
      response. In the future, mdNLR estimates may be used as a valuable research tool
      to reliably estimate SI in the absence of freshly collected blood samples.

PMID- 30186881
TI  - Frequency of Hospitalized Infections Is Reduced in Rheumatoid Arthritis Patients
      Who Received Biological and Targeted Synthetic Disease-Modifying Antirheumatic
      Drugs after 2010.
AB  - Background: Biological disease-modifying antirheumatic drugs (bDMARDs) and
      targeted synthetic (ts) DMARDs are important in rheumatoid arthritis (RA)
      treatment. The risk of hospitalized infection associated with bDMARDs/tsDMARDs in
      RA patients is unclear. Methods: We retrospectively analyzed the cases of the 275
      RA patients with 449 treatment episodes who were administered a bDMARD/tsDMARD at
      Nagasaki University Hospital in July 2003-January 2015. We determined the
      incidence and risk factors of infection requiring hospitalization in the patients
      during a 3-year observation period. Results: Thirty-five (12.7%) of the patients
      experienced a hospitalized infection. The hospitalized infection risk did not
      differ significantly among several bDMARDs/tsDMARDs. A multivariate analysis
      revealed that the comorbidities of chronic lung disease (adjusted HR 5.342, 95%
      CI 2.409-12.42, p < 0.0001) and the initiation of bDMARDs/tsDMARDs before 2010
      (adjusted HR 4.266, 95% CI 1.827-10.60, p = 0.0007) are significant independent
      risk factors for hospitalized infection. Compared to the before-2010 group, the
      group of patients whose treatment initiated in 2010 or later showed higher
      patient ages at the initiation of bDMARD/tsDMARD treatment and a higher rate of
      the use of prophylaxis with an antituberculosis agent, whereas the disease
      activities and number of the patients who received >5 mg of prednisolone were
      lower in the after-2010 group. Conclusions: This is the first report that the
      frequency of hospitalized infection significantly decreased when the patients
      were treated with a bDMARD or tsDMARD after 2010. Our results indicate that the
      updated announcement of diagnosis and treatment criteria might contribute to a
      reduced risk of hospitalized infection and a better understanding of the use of
      bDMARDs/tsDMARDs by rheumatologists.

PMID- 30186882
TI  - Effects of Systemic Simvastatin on the Concentrations of Visfatin, Tumor Necrosis
      Factor-alpha, and Interleukin-6 in Gingival Crevicular Fluid in Patients with
      Type 2 Diabetes and Chronic Periodontitis.
AB  - Purpose: The objective of this study is to explore the relationship between the
      levels of interleukin- (IL-) 6, tumor necrosis factor- (TNF-) alpha, and visfatin
      and simvastatin usage, in the gingival crevicular fluids (GCFs) of diabetic
      patients afflicted with chronic periodontitis. Methods: Eighty outpatients at the
      Periodontology Department, Faculty of Dentistry, University Dental Hospital (King
      Abdulaziz University), were categorized into 4 groups (20 patients per group), on
      the basis of radiological evaluation of bone loss, clinical attachment levels
      (CAL), probing depth (PD), and gingival indices: group 1 (healthy periodontium),
      group 2 (chronic periodontitis + type 2 diabetes), group 3 (chronic
      periodontitis), and group 4 (type 2 diabetes + chronic periodontitis +
      simvastatin). Enzyme-linked immunosorbent assays were used to measure IL-6, TNF
      alpha, and visfatin levels. Results: Significantly elevated levels of IL-6, TNF
      alpha, and visfatin were seen in group 2 in comparison to groups 1 and 3. Reduced
      levels were seen in group 4 due to simvastatin usage. Positive association was
      seen between periodontal variables and the levels of IL-6, TNF-alpha, and
      visfatin. Conclusion: Periodontal destruction and diabetes have a synergistic
      effect on the elevation of inflammatory cytokine levels. Simvastatin may be
      beneficial in improving periodontal health among diabetic patients.

PMID- 30186883
TI  - Effectiveness of Systematic Periodontal Treatment in Male HIV-Infected Patients
      after 9 Years: A Case Series.
AB  - Objective: To investigate effectiveness of systematic periodontal treatment in
      the long term in HIV-infected patients undergoing highly active antiretroviral
      treatment. Methods: Longitudinal, prospective, open-label case series over a
      period of nine years. Periodontal treatment was performed by scaling and root
      planing and supportive periodontal care (SPC) at regular intervals. To measure
      effectiveness, reductions of pocket probing depths were defined as primary study
      endpoint. Results: During the study period, there was a proportional increase in
      periodontal pockets >=4 mm of +53% and in pockets >= 6 mm of +100%. Mean pocket
      depth reductions on patient's level were, however, 0.4 mm nine years after
      scaling and root planing and supportive periodontal care (p=0.180). No teeth were
      lost during the observation period. Conclusions: In terms of best evidence
      available, it is concluded that systematic periodontal treatment including SPC is
      effective in virologically controlled HIV infection and can be performed in
      dental practice safely.

PMID- 30186884
TI  - Utilization of Imaging to Identify a Benign Condition Mimicking Acute
      Appendicitis in a Child.
AB  - One of the most concerning causes of abdominal pain affecting children is acute
      appendicitis. However, there are benign conditions that can closely mimic
      appendicitis in children. In this article, we present a case of a child admitted
      for possible acute appendicitis and determined to have a condition known as
      omental infarction. The patient was managed medically and made a full recovery
      without surgical intervention. The aim of this case report is to review omental
      infarction and present a way of differentiating this disease from appendicitis,
      utilizing imaging, with the goal of avoiding surgical intervention. We also
      discuss the presentation and imaging findings of and another closely related
      condition-epiploic appendagitis. It is important to differentiate appendicitis
      from these 2 conditions as they can be often managed medically without surgical
      intervention.

PMID- 30186885
TI  - A Rare Case of Acute Pancreatitis Due to Very Severe Hypertriglyceridemia (>10
      000 mg/dL) Successfully Resolved With Insulin Therapy Alone: A Case Report and
      Literature Review.
AB  - A 48-year-old male presented to the psychiatric emergency room for dysmorphic
      mood. He was admitted to medical service for the management of hyponatremia,
      which was discovered in his initial laboratory workup. After the first day of
      admission, he developed abdominal pain and fever, and subsequent laboratory work
      revealed a triglyceride level of 10 612 mg/dL (reference range = 0-194 mg/dL).
      Computed tomography scan of the abdomen and pelvis revealed a hypodense lesion in
      the pancreas surrounded by a moderate amount of peripancreatic fluid suggestive
      of hemorrhagic pancreatitis. Based on the laboratory findings and imaging, we
      diagnosed acute pancreatitis (AP) secondary to hypertriglyceridemia. The patient
      was initiated on intravenous fluids and insulin to help decrease the triglyceride
      level with the plan to initiate apheresis. However, the patient improved on
      insulin therapy alone, which negated the need for apheresis, and the patient was
      discharged with fenofibrate with no further complications. While elevated
      triglycerides are a well-known cause of AP, we sought to assess various treatment
      options in management, especially considering a severely elevated triglyceride
      level of >10 000 mg/dL. Along with supportive care in AP, there are additional
      options in hypertriglyceridemia AP, including heparin, insulin, apheresis,
      antioxidants, and fibrates. Currently, there are no clear guidelines favoring one
      therapeutic option over the other.

PMID- 30186886
TI  - An Atypical Presentation of Tuberculomas in an Immunocompetent Host.
AB  - Tuberculomas are an intracranial form of tuberculosis that account for a third of
      intracranial lesions in endemic areas. If symptomatic, they usually present as
      meningitis in an immunocompromised host; however, in patients without signs of
      meningitis, clinical features are essentially indistinguishable from any other
      space-occupying lesion. We present a case of central nervous system tuberculosis
      in an immunocompetent host who presented with new-onset seizures.

PMID- 30186887
TI  - Erratum.
AB  - [This corrects the article DOI: 10.1093/ofid/ofy081.][This corrects the article
      DOI: 10.1093/ofid/ofy081.].

PMID- 30186888
TI  - Single Academic Center Experience of Unrestricted beta-d-Glucan Implementation.
AB  - We investigated serum beta-d-glucan (BDG) testing among non-neutropenic adult
      inpatients at an academic center where the test is unrestricted. BDG orders were
      inappropriate in 49% of cases due to absence of predisposing host factors or
      clinical picture consistent with fungal infection. Providers' knowledge about BDG
      was insufficient.

PMID- 30186889
TI  - Successful Treatment of a Renal Abscess Caused by Mycobacterium chelonae: A Case
      Report.

PMID- 30186890
TI  - Disseminated Mycobacterium abscessus Infection Secondary to an Infected Vascular
      Stent: Case Report and Review of the Literature.
AB  - Mycobacterium abscessus is a rapidly growing, multidrug-resistant mycobacteria,
      commonly associated with pulmonary, skin, and soft tissue infections. We describe
      a rare case of M abscessus endovascular stent infection; only 3 cases of graft
      infections have previously been reported.

PMID- 30186892
TI  - An up-dated meta-analysis of major adverse cardiac events on triple versus dual
      antiplatelet therapy after percutaneous coronary intervention in patients with
      type 2 diabetes mellitus.
AB  - This meta-analysis is conducted to assess the efficiency and safety of triple
      antiplatelet therapy in patients with type 2 diabetes mellitus (T2DM) who have
      received coronary stents implantation. The risk of major adverse cardiac events
      (MACEs), target vessel revascularization (TVR), target lesion revascularization
      (TLR), myocardial infarction (MI) and bleeding events were evaluated in this meta
      analysis. Eight randomized controlled trials incorporating 1700 participants were
      included. During a follow-up of 12 months after stents implantation, the risk of
      TVR, TLR and MACEs in Triple group were lower than that of Dual group. There was
      no significant difference in the comparison of stent thrombosis and bleeding
      events between the two groups. Triple antiplatelet therapy is effective in
      reducing adverse cardiovascular outcomes in T2DM patients after stents
      implantation, without increasing the risk of bleeding events. Advanced designed
      and large-scale trails are deserved in the future.

PMID- 30186891
TI  - The Impact of Multiple Dimensions of Socioeconomic Status on Physical Functioning
      Across the Life Course.
AB  - Objective: We used the Physical Performance Across the LifeSpan Study to
      investigate the relationships of multiple indicators of socioeconomic status
      (SES), both in early life and late life, with physical function. Method: We
      examined associations between multiple early and late life SES indicators with
      physical function measured by aerobic endurance, gait speed, and lower body
      strength. Results: Higher participant education and household income were
      associated with increased physical function. In our age-stratified analysis, we
      observed widening SES disparities with increasing age among those in the two
      younger strata with lower SES associated with worse physical function. Finally,
      we observed an association between socioeconomic trend and gait speed, aerobic
      endurance, and lower body strength. There was also an association between lower
      aerobic endurance and being in a downward socioeconomic trend. Discussion: These
      findings highlight the significance of considering multiple dimensions of the
      social environment as important correlates of physical functioning across the
      life course.

PMID- 30186893
TI  - Data on seed priming and seedling growth of Barli 21 tobacco varieties under
      polyethylene glycol and salinity stress conditions.
AB  - Data on the effect of seed priming on Barli 21 tobacco (Nicotiana tobacum L.)
      cultivars, an experiment was carried out in 2014 at the Tobacco Research center
      of Urmia, Iran under saline and Polyethylene glycol conditions. This experiment
      was arranged as factorial, based on RCB design with three replications.
      Treatments were polyethylene glycol (- 0.5%, - 1%, - 1.5% and - 2% (PEG) and
      hydropriming, and salinity levels (1, 2, 3 and 4 dS m-1 KNO3) in periods 1, 2, 3,
      5 and 10 days. Means of Emergence time, emergence rate coefficient, Emergence
      rate index, Emergence rate, and Emergence percentage decreased with increasing
      salinity. Emergence time and emergence rate coefficient increased with
      hydropriming in priming 5 and 10 days. Emergence rate index, Emergence rate, and
      Emergence percentage increased with 1.5% Polyethylene glycol. Seed priming with
      Polyethylene glycol was more beneficial in improving Emergence percentage,
      compared with KNO3 priming.

PMID- 30186894
TI  - The differentially mitochondrial proteomic dataset in human ovarian cancer
      relative to control tissues.
AB  - This data article presents a differentially mitochondrial proteomic dataset in
      human ovarian cancer tissues relative to control tissues. The mitochondrial
      samples were prepared from human ovarian cancer and control ovary tissues, and
      were digested with trypsin. The tryptic peptides from ovarian cancer and control
      mitochondrial samples were labeled by isobaric tags for relative and absolute
      quantification (iTRAQ) reagents, followed by strong-cation exchange (SCX)
      chromatography, liquid chromatography (LC)-tandem mass spectrometry (MS/MS), and
      bioinformatic analysis. This data article is related to a published article (Li
      et al., 2018) [1].

PMID- 30186895
TI  - Data on investigating the nitrate concentration levels and quality of bottled
      water in Torbat-e Heydarieh, Khorasan razavi province, Iran.
AB  - The human body is primarily water and healthy drinking water is vital to human
      life. Today, the bottled-water industry has been widely developed in most
      countries and more than 150 several brands of bottled water are produced in Iran.
      Considering the increasing consumption of bottled water and its potential for
      contamination with harmful chemical and microbial agents such as nitrate, the aim
      of this study was to assess the nitrate concentration and also the microbial
      quality of bottled water in a number of brands produced in the Torbat-e Heydarieh
      city in 2017. In present descriptive-analytical research, random sampling (80
      samples) was done by collecting 1.5 l bottled water with different production
      dates from 20 factories. These samples were collected in four different seasons.
      Measurement of nitrate concentration and microbial quality including total and
      fecal coliforms, were performed according to the Standard Methods for the
      Examination of Water and Wastewater. The results indicated that, in general, the
      mean concentration of nitrate in all samples was range 0.6-16 mg/L and all
      samples are within the national standard of Iran (less than 50 mg/L) and
      international standards. Also, total coliforms and fecal coliforms in any of the
      studied samples were zero.

PMID- 30186896
TI  - NGS-dataset of putative driver mutations associated with benign peritoneal
      strumosis.
AB  - A rare case of benign peritoneal strumosis was screened for driver mutations in
      genes relevant to currently approved cancer therapies. Therefore, three formalin
      fixed paraffin embedded issue sections were screened with the GeneReader
      Actionable Insights NGS panel (Qiagen, Hilden, Germany) for the occurrence of
      driver mutations. Several mutations were identified in drug-targetable genes,
      such as ALK, EGFR, and BRAF. The majority of identified mutations were single
      nucleotide variant, but also a insertion/deletion mutation was identified. The
      presented dataset is the first NGS dataset available from a patient with benign
      peritoneal strumosis.

PMID- 30186899
TI  - Where are we now? Expanding AAHKS internationally.

PMID- 30186897
TI  - Data for designing two isothermal amplification assays for the detection of root
      infecting fungi on cool-season turfgrasses.
AB  - Loop-mediated isothermal amplification (LAMP) and recombinase polymerase
      amplification (RPA) are two rapid isothermal amplification methods for detecting
      three common fungal root pathogens of cool-season turfgrass: Gaeumannomyces
      avenae, Magnaporthiopsis poae and Ophiosphaerella korrae, "Detection of root
      infecting fungi on cool-season turfgrasses using loop-mediated isothermal
      amplification and recombinase polymerase amplification" (Karakkat et al., 2018)
      [1]. The data provided here describe the information for designing primers and
      probes for LAMP and RPA, how specific they are for each of the three fungi, and
      the evaluation of RPA on field samples.

PMID- 30186898
TI  - Data on dielectric strength heterogeneity associated with printing orientation in
      additively manufactured polymer materials.
AB  - The following data describe the dielectric performance of additively manufactured
      polymer materials printed in various orientations for four common additive
      manufacturing techniques. Data are presented for selected commercial 3D printing
      materials fabricated using four common 3D printing techniques: Stereolithography
      (SLA), Fused Deposition Modeling (FDM), Selective Laser Sintering (SLS), and
      Polymer Jetting (PolyJet). Dielectric strengths are compiled for the listed
      materials, based on the ASTM D139 standard. This article provides data related to
      "Dielectric Strength Heterogeneity Associated with Printing Orientation in
      Additively Manufactured Polymer Materials" [1].

PMID- 30186900
TI  - Small-colony variant of Staphylococcus lugdunensis in prosthetic joint infection.
AB  - Prosthetic joint infection is usually caused by staphylococci. Among the
      coagulase-negative staphylococci, Staphylococcus lugdunensis is important because
      it behaves as a pathogen similar to S aureus. It also develops biofilms, and the
      biofilm phenotype can appear as small-colony variants. Although genetically
      indistinguishable, they differ in size and antibiotic susceptibility from the
      parent strain and are responsible for chronic persistent infection and failure of
      antibiotic treatment. They can also lead to misinterpretation of results. The
      patient reported here underwent total knee replacement and 2 years later
      presented with prosthetic joint infection. Tissue samples and prosthesis taken at
      revision grew S lugdunensis, the majority of which were small-colony variants.
      Recommendations are made for their detection and identification.

PMID- 30186901
TI  - A case of bilateral hip mechanically assisted crevice corrosion after staged
      total hip arthroplasty.
AB  - Mechanically assisted crevice corrosion (MACC), also known as trunnionosis, and
      adverse local tissue reaction (ALTR) are entities that can lead to pain and
      necessitate revision in total hip arthroplasty (THA). We present a case of a 75
      year-old female who received a bilateral staged primary THA with metal on cross
      linked polyethylene implants and had subsequent bilateral revisions for MACC and
      ALTR. In both instances, she presented with anterior thigh pain, weakness, and
      difficulty ambulating, and she was revised to ceramic on cross-linked
      polyethylene implants. This case may suggest a biologic predisposition or
      systemic immunogenic reaction to metal debris in some patients with ALTR or
      represent an implant-specific complication. To our knowledge, this is the first
      case reported of a patient having bilateral MACC from staged THA performed by 2
      different surgeons using the same brand implant.

PMID- 30186902
TI  - Disassembly of the inner head of a bipolar hip prosthesis.
AB  - We report an extremely rare case of inner head displacement from the stem of a
      bipolar hip prosthesis (BHP). An 88-year-old woman underwent BHP implantation for
      right femoral neck fracture. However, severe right hip joint pain occurred 12
      days after surgery. A plain radiogram film revealed displacement of the inner
      head from the neck of the stem, accompanied by sinking of the stem. At
      reoperation, the inner head was disassembled from the stem, and Vancouver type A1
      fracture was confirmed. Disassembly may have been caused by the pumping
      phenomenon or micromovement of the stem due to periprosthetic fracture. To our
      knowledge, this is the first report about disassembly of the BHP inner head,
      probably due to periprosthetic fracture.

PMID- 30186903
TI  - Catastrophic failure of tripolar constrained liners due to backside wear: a novel
      failure mode.
AB  - Constrained acetabular liners have been developed for patients who are at high
      risk for dislocation or who are undergoing revision surgery for recurrent
      dislocations. We report on 2 cases of failure of tripolar constrained liners due
      to severe backside polyethylene wear after dissociation of the outer polyethylene
      liner without dislocation, a mode of failure not previously reported. The
      backside of the inserts suffered severe polyethylene deformation, wear, and
      scratching due to dissociation from the locking mechanism. In patients with
      tripolar constrained liners, radiographic evidence of eccentric wear should be
      considered as possible occult dissociation of the polyethylene liner within the
      shell. Conversion to a modular dual mobility liner appears to be a viable
      solution in this setting.

PMID- 30186904
TI  - Catastrophic failure of a dual mobility bearing in a revision total hip
      arthroplasty.
AB  - The following case demonstrates an example of a catastrophic failure of a dual
      mobility (DM) bearing used in the setting of a revision total hip arthroplasty
      for an acetabular component with an excessive abduction angle. Currently, in the
      literature, it has been demonstrated that DM bearings have decreased polyethylene
      wear at abduction angles up to 65 degrees ; however, this has only been shown in
      in vitro studies. To our knowledge, there have been no reports of in vivo DM
      bearings that have demonstrated these same results. In this case, a DM bearing
      was used in a revision surgery with a retained acetabular component that had an
      abduction angle of approximately 70 degrees -75 degrees  which ultimately led to
      catastrophic polyethylene failure.

PMID- 30186905
TI  - Total hip arthroplasty and femoral nail lengthening for hip dysplasia and limb
      length discrepancy.
AB  - The application of distraction osteogenesis through the use of magnet-operated,
      remote-controlled intramedullary lengthening continues to provide new
      opportunities for accurate limb equalization. While limb-length discrepancy and
      deformity can be addressed by total hip arthroplasty alone, the magnitude of
      correction is limited by the soft-tissue envelope and complications such as
      sciatic nerve palsy. This 3-patient case series presents the combination of
      staged ipsilateral total hip arthroplasty and retrograde intramedullary femoral
      nail lengthening for the correction of both deformity and limb-length
      discrepancy. Our results report leg-length equalization, independent ambulation
      without assistive devices, and excellent bone and functional outcomes without
      complications, demonstrating that this combined technique can be used to achieve
      targeted lengthening and deformity correction.

PMID- 30186906
TI  - Superior rim fracture of a vitamin E-infused highly cross-linked polyethylene
      (HXLPE) liner leading to total hip arthroplasty revision.
AB  - This case report looks at the failure of a vitamin E-infused highly cross-linked
      polyethylene acetabular liner that fractured at the superior rim of the locking
      mechanism. This calls to question whether there is a problem with the vitamin E
      infused product or a flaw in the design of the liner or possibly a combination of
      the 2. Although there has been discussion of a possible minimum rim polyethylene
      thickness, there has not been a minimum thickness established. In addition, in
      the case of offset liners, indentations which are a part of a locking mechanism
      can cause the minimum rim dimension to be much less than the specified nominal
      thickness. This case serves as an interesting observation and contributes to the
      discussion of rim liner polyethylene thickness and minimum rim thickness.

PMID- 30186907
TI  - A case of bone necrosis with pseudotumor following metal-on-metal total hip
      arthroplasty.
AB  - A case of bone necrosis with a pseudotumor following metal-on-metal total hip
      arthroplasty is presented. The patient showed no abnormal magnetic resonance
      findings 2 years postoperatively, but serum metal ion levels were elevated. The
      patient developed hip pain 3.5 years postoperatively, and bone necrosis with a
      pseudotumor was found. The present patient emphasized the fact that tissue
      necrosis associated with failed metal-on-metal bearing hip might not be limited
      to soft tissues, but bone necrosis could occur.

PMID- 30186908
TI  - Fracture of an S-ROM stem at the sleeve-stem junction.
AB  - Fracture of a well-ingrown femoral component is a rare and often challenging
      complication. Modular junctions and sleeve interfaces have been identified as one
      potential point of weakness with corrosion and fretting being contributing
      factors to ultimate femoral component fracture. Stem fractures at the sleeve
      interface were reported occasionally for the proximal ingrowth modular Emperion
      System (Smith and Nephew, Memphis, TN). However, this failure mechanism has been
      reported infrequently, often associated with corrosion at the modular junction,
      for the similarly designed S-ROM system (DePuy Orthopedics Inc., Warsaw, IN). We
      present the case of a 52-year-old patient, with a body weight of 84 kg (185 lbs)
      and a body mass index of 30.6 kg/m2, who suffered a fatigue fracture of a 14 * 09
      * 130 mm S-ROM stem 42 months after implantation. The present study presents the
      results of the surface analysis, discusses possible failure mechanisms, provides
      treatment guidelines, and a review of the literature revealing 15 cases of
      failure at the level of the stem-sleeve junction. In particular, modifiable risk
      factors for potential stem failure, including stem diameter, stem offset, and the
      resulting cantilever bending forces on the proximal sleeve-stem junction, are
      discussed in detail.

PMID- 30186909
TI  - Fracture risk of tapered modular revision stems: a failure analysis.
AB  - Fractures of well-ingrown femoral components are a rare and often challenging
      complication after revision total hip arthroplasty. Prior series have documented
      catastrophic failure at the modular junction of revision femoral components.
      However, to the authors' knowledge, there has been only 1 report of a mid-stem
      fracture of a modular tapered revision stem. The present article reports 2 cases
      of fatigue fractures (14 months and 10 years after implantation) of a tapered
      modular revision stem. It presents the results of the fracture surface analysis,
      discusses the etiology of failure, and presents the authors' recommendations on
      how to best avoid this complication.

PMID- 30186910
TI  - What can the surgeon do to reduce the risk of junction breakage in modular
      revision stems?
AB  - Modular revision stems are very common in hip arthroplasty, but junction fracture
      remains a known failure mechanism. A review of the literature with description of
      cases with junction breakage of modular revision stems showed that in all 24
      analyzed cases, there was a common finding: the combination of an effective
      osteointegration of the distal component and missing medial bone support of the
      proximal component. The result was a bending stress point of the stem
      construction in the region of the junction. A technique using the combination of
      short distal component and longer proximal components may alter this stress
      pattern, allow proximal implant support, and reduce the risk of junction
      fracture. Moreover, filling of gaps between the modular component and the medial
      region of the femoral calcar in endofemoral implantation, a double osteotomy in
      significant bowed femurs, and treating medial bone defects with structural
      allografts additionally can reduce the risk of junction breakage.

PMID- 30186911
TI  - Shoelace capsular and external rotators closure techniques in posterior
      (southern) approach to hip joint.
AB  - The possible increased risk of dislocation with a posterior approach for femoral
      hemiarthroplasty is attributed to disruption of the posterior soft-tissue
      structures, including the posterior capsular ligament structure and short
      external rotators of the hip. In this surgical technical note, we demonstrate the
      surgical technique for shoelace suturing of the external rotators and the capsule
      with use of ULTRATAPE. After prosthesis stem insertion, shoelace suturing using
      ULTRATAPE was performed between the great trochanter and the external rotators
      for preventing the external rotators from tearing. Also, ULTRATAPE was sewed
      alternately on the split capsule like shoe lacing, and it was laced up from
      proximal to distal in line with the split as shoelaces tied down. The shoelace
      suturing technique using ULTRATAPE after a posterior approach to the hip joint,
      possibly lowers risks of tearing hip capsular ligament and external rotators and
      stabilizes the posterior wall.

PMID- 30186912
TI  - Acetabular wedge augments for uncontained tibial plateau defects in revision
      total knee arthroplasty.
AB  - : Tibial bone loss is a common scenario encountered during revision total knee
      arthroplasty. Reconstructive options depend on the amount and location of bone
      loss, but few good solutions exist to address large, uncontained tibial defects
      where cortical support is lost in the metadiaphyseal region. We describe a novel
      technique using acetabular augments to buttress a revision tibial component and
      recreate a hemiplateau during tibial revision total knee arthroplasty. In
      selected scenarios, this construct can create a biomechanically friendlier
      surface onto which to support the tibial tray and a less expensive option when
      compared to traditional stacked augments or cones. Level of Evidence: IV-Case
      series.

PMID- 30186913
TI  - Radiographic assessment and clinical outcomes after total knee arthroplasty using
      an accelerometer-based portable navigation device.
AB  - It has been reported that an accelerometer-based portable navigation device can
      achieve accurate bone cuts, but there have been few studies of clinical outcomes
      after total knee arthroplasty (TKA) using such a device. The aim of this study
      was to evaluate lower limb alignment and clinical outcomes after TKA using an
      accelerometer-based portable navigation device. Thirty-five patients (40 knees)
      underwent primary TKAs using an accelerometer-based portable navigation device.
      Postoperative radiographic assessments included the hip-knee-ankle angle, femoral
      component angle (FCA), and tibial component angle (TCA) in the coronal plane and
      the sagittal FCA and sagittal TCA in the sagittal plane. Clinical outcomes were
      evaluated by the Japanese Orthopedic Association score for osteoarthritic knees,
      Japanese Knee Osteoarthritis Measure, and the New Knee Society Score. The
      frequency of outliers (>3 degrees) was 10% for the hip-knee-ankle angle, 8% for
      FCA, 0% for TCA, 19% for sagittal FCA, and 9% for sagittal TCA. The Japanese
      Orthopedic Association score and Japanese Knee Osteoarthritis Measure were
      significantly improved postoperatively. The postoperative New Knee Society Score
      was 67.2% for symptoms, 50.3% for satisfaction, 58.6% for expectation, and 44.1%
      for function. TKA using an accelerometer-based portable navigation device
      achieved good results for both lower limb alignment and clinical outcomes.

PMID- 30186914
TI  - Empiric treatment is less costly than Staphylococcus aureus screening and
      decolonization in total joint arthroplasty patients.
AB  - The aim of our study was to compare the cost of preoperative empiric mupirocin
      treatment of all total joint arthroplasty patients with a standard Staphylococcus
      aureus screening and decolonization protocol. The cost of empiric mupirocin
      treatment is $24.65 per patient, whereas the cost of a standard S. aureus
      screening and decolonization protocol is $60.32 per patient. Given that more than
      1,051,000 total joint arthroplasties are performed annually, the cost savings
      with empiric treatment is nearly $40 million per year. Empiric treatment allows
      for more efficient workflow, minimizes potential for clerical error, eliminates
      risk of undertreatment, and has not been shown to increase antibiotic resistance.

PMID- 30186915
TI  - Total knee arthroplasty in patients with multiple hereditary exostoses.
AB  - We present a case report of a patient with severe valgus deformity of the right
      knee due to multiple hereditary exostoses (MHEs) treated with total knee
      arthroplasty (TKA). The surgical management of MHE affecting the knee encompasses
      exostoses resection, joint deformity rectification, and limb-length discrepancy
      alignment. On rare occasions, distraction osteogenesis and TKA have been used to
      correct valgus deformities of the knee. TKA in MHE patients with knee involvement
      has only been described in 6 cases. Several considerations, such as extensive
      knowledge of frequently occurring skeletal aberrations, are required to
      successfully correct the deformities associated with MHE via TKA. This report
      describes a case of severe valgus knee deformity with a rotational component in
      MHE managed with TKA, the surgical technique, and future recommendations.

PMID- 30186916
TI  - Primary lower limb joint replacement and tranexamic acid: an observational cohort
      study.
AB  - Background: This work aimed to evaluate the efficacy and safety of routine
      tranexamic acid (TXA) use in elective orthopaedic lower limb joint replacement
      surgery. Methods: This retrospective cohort study included all primary hip or
      knee replacement procedures by a single surgeon over a 6-year period. TXA was
      introduced during the study period as part of an enhanced recovery after surgery
      strategy. Results: Of the 673 procedures, 446 cases (66.3%) received TXA. The
      median length of stay was 5 days (2-69) and 6 days (3-28) for the TXA and control
      groups, respectively (P < .001). Blood transfusion was required for 28 (6.3%) of
      the TXA cases versus 40 (17.6%) controls (P < .001). Complication rates were
      similar irrespective of TXA status. At multivariate analysis, TXA was
      significantly and independently associated with fewer blood transfusions (hazard
      ratio 0.309, 95% confidence interval: 0.168-0.568, P < .001), with a number
      needed to treat of 9 cases. TXA use was estimated to save between L67.89 and
      L155.90 per case. Conclusions: Routine prophylactic TXA administration for
      elective primary hip and knee replacement reduces the likelihood of postoperative
      transfusion with a number needed to treat of 9. Cost savings may be as high as
      L155.90 per case, and no safety concerns were noted.

PMID- 30186917
TI  - Cost and determinants of acute kidney injury after elective primary total joint
      arthroplasty.
AB  - Background: Acute kidney injury (AKI) is a serious complication after major
      surgery, which may lead to increased morbidity and mortality. The aim of this
      study was to identify cost and determinants of AKI after total joint
      arthroplasty. Methods: A retrospective case-controlled study was conducted with
      1719 primary elective total hip or knee replacements performed from January 2004
      through September 2015 at an urban teaching hospital. Patients who developed AKI
      were matched in a 1:3 ratio with those in a control group who did not develop AKI
      based on age, sex, race, operated joint, and comorbidities including hypertension
      and diabetes. Increased postoperative serum creatinine was considered indicative
      of AKI. Results: Fifty-four patients (3.1%) had AKI that was significantly
      associated with increased length of hospital stay (8.07 days) compared with that
      of the control group (4.50 days, P < .0001) and incurred significantly higher
      hospital charges ($224,533) than those of the control group ($142,753, P <
      .0001). We identified high body mass index, undergoing bilateral surgery in one
      session, high estimated blood loss, and longer duration of surgery as significant
      risk factors for AKI in univariate analysis. Elevated preoperative creatinine,
      large postoperative drop in hemoglobin, and high American Society of
      Anesthesiologists physical status scores were significant independent predictors
      of AKI in multivariate analysis. Conclusions: Health-care providers and patients
      should work together to manage risk factors and to lower the risk of morbidity
      and mortality, longer in-hospital stay, and high associated costs of AKI.

PMID- 30186918
TI  - A dedicated anticoagulation clinic does not improve postoperative management of
      warfarin after total joint arthroplasty.
AB  - Background: Periprosthetic joint infections (PJIs) are devastating complications.
      Excessive anticoagulation with warfarin is an independent risk factor for PJIs.
      The use of a dedicated anticoagulation clinic to improve warfarin management has
      not been proven. Methods: Between 2006 and 2014, we identified 92 patients who
      were placed on postoperative warfarin, and later developed PJI. These patients
      were compared to 313 patients who underwent total joint arthroplasty placed on
      warfarin without developing PJI. Patients were included if they had no history of
      a venous thromboembolic event, were warfarin naive, and enrolled in the
      anticoagulation clinic. A univariate analysis compared independent variables, and
      statistical analysis was performed using Student's t-test and Pearson chi-square
      test for continuous and categorical variables. Results: Thirty-six PJI patients
      and 297 control patients met the inclusion criteria. The venous thromboembolism
      rate was 2.1%. At discharge, 82% of all patients were subtherapeutic. Patients
      were within their target international normalized ratio (INR) range 26.7% of the
      time. The mean INR in the initial postoperative period for the PJI group was 1.46
      and 1.29 in the control group (P < .001). In the acute postoperative period,
      13.3% of the knee PJI group were therapeutic or supratherapeutic compared with
      3.5% in the knee control group (P = .002). Conclusions: Despite utilization of a
      dedicated anticoagulation clinic, patients were only within their target INR
      range 27% of the time. Total knee arthroplasty patients who developed a PJI were
      more likely to be therapeutic or supratherapeutic in the initial postoperative
      period. Consequently, the risks associated with warfarin as a venous
      thromboembolism prophylaxis may outweigh the potential benefits.

PMID- 30186919
TI  - What are the incidence and risk factors of in-hospital mortality after venous
      thromboembolism events in total hip and knee arthroplasty patients?
AB  - Background: Pulmonary embolism and deep vein thrombosis, together referred to as
      venous thromboembolism (VTE), are serious and potentially preventable
      complications after total hip arthroplasty and total knee arthroplasty. The aim
      of this study was to investigate the incidence of mortality after VTE events and
      assess the risk factors that are associated with it. Methods: The Nationwide
      Inpatient Sample was used to estimate the total number of total hip arthroplasty,
      total knee arthroplasty, VTE events, and mortality using the International
      Classification of Diseases, Ninth Revision procedure codes from 2003 to 2012.
      Patients' demographics, Elixhauser, and Charlson comorbidity indices were used to
      identify the risk factors associated with in-hospital VTEs and mortality.
      Results: A total of 1,805,621 THAs and TKAs were included. The overall rate of
      VTE was 0.93%. The in-hospital mortality rate among patients with VTEs was 7.1%
      vs 0.30% in patients without VTEs (P-value < .0001). The risk factors for
      mortality after VTE events in descending order were as follows: hypercoagulable
      state (odds ratio [OR]: 5.3, 95% confidence interval [CI]: 3.6-5.8), metastatic
      cancer (OR: 5.2, 95% CI: 3.3-5.6), myocardial infarction (OR: 4.2, 95% CI: 2.3
      4.7), peripheral vascular disease (OR: 3.6, 95% CI: 3.2-4.0), cardiac arrhythmias
      (OR: 3.2, 95% CI: 1.6-4.3), advanced age (OR: 3.1, 95% CI: 2.3-3.7), electrolyte
      disorders (OR: 3.1, 95% CI: 2.2-3.6), pulmonary circulation disorders (OR: 2.9,
      95% CI: 2.6-3.3), depression (OR: 2.8, 95% CI: 1.6-3.4), complicated diabetes
      (OR: 2.7, 95% CI: 2.1-3.2), weight loss (OR: 2.6, 95% CI: 2.2-3.3), renal failure
      (OR: 2.6, 95% CI: 1.7-3.5), chronic pulmonary disease (OR: 2.5, 95% CI: 1.3-3.1),
      valvular disease (OR: 2.4, 95% CI: 1.8-2.7), liver disease (OR: 1.7, 95% CI: 1.2
      1.9), and obesity (OR: 1.6, 95% CI: 1.5-1.9). Conclusions: In-hospital VTE has a
      significant in-hospital mortality rate. Several of the identified risk factors in
      this study are modifiable preoperatively. We strongly urge the orthopaedic
      community to be cognizant of these risk factors and emphasize on optimizing
      patients' comorbidities before an elective arthroplasty.

PMID- 30186920
TI  - Learning curve with a new primary total knee arthroplasty implant: a multicenter
      perspective with more than 2000 patients.
AB  - Background: This study provides an example for evaluating learning curve when
      introducing a new knee system. Methods: Thirty-five investigators across 22 sites
      prospectively implanted 843 subjects with currently available products (group A).
      Seventy-seven investigators across 48 sites prospectively implanted 2330 subjects
      with the ATTUNE Knee System; in which the first 10 subjects for each surgeon were
      the learning curve cases (group B, N = 611), and the later subjects were
      designated as group C (N = 1719). Surgical time, rates of intraoperative and
      early postoperative complications, and patient-reported outcome measures (PROMs)
      at a minimum of 1 year were compared. Results: Mean (standard deviation) surgical
      time was 72.0 (21.6) minutes for group A, 83.0 (24.2) for group B, and 72.1
      (24.1) for group C (P < .001 for group B vs group C; P = .955 for group C vs
      group A). Intraoperative, early (<90 day) complication rates, and PROMs were
      similar for all groups. Conclusions: The new knee system learning curve was
      characterized by a slightly longer surgical time with no negative impact on
      complications or PROMs. Level of Evidence: III.

PMID- 30186921
TI  - Medicaid is associated with increased readmission and resource utilization after
      primary total knee arthroplasty: a propensity score-matched analysis.
AB  - Background: Medicaid payer status has been shown to affect resource utilization
      across multiple medical specialties. There is no large database assessment of
      Medicaid and resource utilization in primary total knee arthroplasty (TKA), which
      this study sets out to achieve. Methods: The Nationwide Readmissions Database was
      used to identify patients who underwent TKA in 2013 and corresponding "Medicaid"
      or "non-Medicaid" payer statuses. Demographics, 15 individual comorbidities,
      readmission rates, length of stay, and direct cost were evaluated. A propensity
      score-based matching model was then used to control for baseline confounding
      variables between payer groups. A chi-square test for paired proportions was used
      to compare readmission rates between the 2 groups. Length of stay and direct cost
      comparisons were evaluated using the Wilcoxon signed-rank test. Results: A total
      of 8372 Medicaid and 268,261 non-Medicaid TKA patients were identified from the
      2013 Nationwide Readmissions Database. A propensity score was estimated for each
      patient based on the baseline demographics, and 8372 non-Medicaid patients were
      propensity score matched to the 8372 Medicaid patients. Medicaid payer status
      yielded a statistically significant increase in overall readmission rates of
      18.4% vs 14.0% (P < .0001, relative risk = 1.31, 95% confidence interval [1.23
      1.41]) with non-Medicaid status and 90-day readmission rates of 10.0% vs 7.4%,
      respectively (P < .001, relative risk = 1.35, 95% confidence interval [1.22
      1.48]). The mean length of stay was longer in the Medicaid group compared with
      the non-Medicaid group at 4.0 days vs 3.3 days (P < .0001) as well as the mean
      total cost of $64,487 vs $61,021 (P < .0001). Conclusions: This study
      demonstrates that Medicaid payer status is independently associated with
      increased resource utilization, including readmission rates, length of stay, and
      total cost after TKA.

PMID- 30186922
TI  - The effect of a preoperative education class on the rate of manipulation under
      anesthesia after total knee arthroplasty in a veterans population.
AB  - Background: Arthrofibrosis after total knee arthroplasty (TKA) is a common
      complication, potentially occurring in up to 25% of patients, and may be treated
      during the early recovery period by manipulation under anesthesia (MUA). The
      majority of preoperative factors that predispose patients to postoperative
      stiffness are patient specific and not modifiable. The United States Veteran
      Affairs is a particularly challenging group given a higher baseline rate of
      medical comorbidities and opioid dependence than the general population. Patient
      education about postoperative expectations and complications has been shown to
      improve outcomes in certain orthopedic procedures. This retrospective study aims
      to determine if preoperative counseling for veterans undergoing primary TKA
      reduces the rate of postoperative stiffness, and consequently MUA, in this subset
      of patients. Methods: We evaluated the medical records of 244 veterans at a
      single veteran affairs hospital who underwent 278 TKAs during a 6-year period
      under one surgeon. Patients were separated into groups based on attendance in the
      preoperative counseling session. Effects of various factors, including age, sex,
      body mass index, preoperative knee range of motion, and history of previous knee
      surgery, were compared between these 2 cohorts. Results: Attendance in the
      preoperative course did not have a statistically significant impact on the rate
      of manipulation (odds ratio [OR], 1.07). Female gender and prior manipulation had
      an increased OR of knee manipulation, whereas age > 65 years had a decreased OR
      that did not reach significance. Conclusions: Our results show that preoperative
      counseling did not have a benefit in terms of postoperative MUA rates in
      veterans. Preoperative education may be helpful for setting appropriate
      expectations of pain, recovery, and function after total joint arthroplasty and
      may be useful in an online or video format in small practices in which cost may
      be prohibitive. Further studies are needed to determine whether they provide any
      benefit in postoperative arthrofibrosis rates.

PMID- 30186923
TI  - Mid-term results of total hip replacement with subtrochanteric osteotomy, modular
      stem, and ceramic surface in Crowe IV hip dysplasia.
AB  - Background: Total hip athroplasty (THA) in Crowe IV developmental dysplasia of
      the hip (DDH) presents many challenges for surgeons with regard to acetabular and
      femoral deformities. The purposes of this study are to (1) report the mid-term
      results of THA with subtrochanteric transverse osteotomy using S-ROM prosthesis
      and ceramic-on-ceramic (COC) surface for Crowe type IV DDH; and (2) compare the
      wear performance between COC and metal-on-polyethylene (MOP) bearing couple.
      Methods: Eighty Crowe IV DDH patients (103 hips) treated with cementless THA were
      retrospectively reviewed. The S-ROM prosthesis was used in all the hips and
      subtrochanteric osteotomy was performed in 74 hips. COC and MOP bearing surfaces
      were compared through the evaluation. Results: At mean follow-up of 65.6 months,
      the mean Harris hip score improved from 54.2 to 87.7 points; however,
      Trendelenberg sign positive was confirmed in 20.4% of the hips. Postoperative
      dislocation occurred in 6 cases and overall 4 hips were revised. With any
      component revision as endpoint, Kaplan-Meier survival curve showed that 8-year
      cumulative survival rate in the COC group was 97.2% and 9-year survival rate in
      the MOP group was 85.9%. The mean linear wear rate for COC and MOP surface was
      0.006 and 0.175 mm/y, respectively. Conclusions: Subtrochanteric osteotomy
      combined with the modular S-ROM prosthesis and COC surface in Crowe IV DDH has
      achieved satisfactory mid-term results. However, postoperative dislocation and
      limp remain major complications. Linear wear rate for MOP surface is high and the
      long-term prosthesis survival is affected. Ceramic or highly cross-linked
      polyethylene should be preferred.

PMID- 30186924
TI  - Dual-taper modular hip implant: Investigation of 3-dimensional surface scans for
      component contact, shape, and fit.
AB  - Background: The etiology of wear particle generation and subsequent corrosion in
      modular total hip arthroplasty implants likely begins with mechanical fretting.
      The purpose of this study was to determine geometric features of the male and
      female taper surfaces that drive stability within the neck-stem junction.
      Methods: Eighteen modular hip components received 3-dimensional surface scans to
      examine the neck-stem taper junction using an optical scanner. The normal
      distance between the surfaces of the neck taper as seated in the stem slot was
      measured and produced a color map of the contact proximity. Contour plots
      identified surface shape variation and contact. Angle measurements and neck
      seated depth were analyzed by regression. Results: The typical features observed
      were (1) a vertical line of contact at one end of the transition from the flat
      surface to the radius surface; (2) a vertical line of contact in the radius
      surface just past the centerline; (3) a concavity along the flat surface between
      the neck and stem components; and (4) one of the neck flat surfaces was closer to
      its mating surface on the stem. The seated depth of the neck was dependent on the
      taper angles in the flat section of the neck (R2 = 0.5000, P = .0332).
      Conclusions: The shape of the neck and stem tapers deviate from ideal design
      dimensions, contributing to relative motions between the neck and stem. While
      these processes are not proven to directly cause implant failure, they may place
      the implants at higher risk for failure.

PMID- 30186925
TI  - Survivorship of a modular acetabular cup system: medium- to long-term follow-up.
AB  - Background: Total hip arthroplasty (THA) requires components that meet a variety
      of patient factors and needs. This investigation evaluated survivorship of the
      PINNACLE Acetabular Cup System in primary total hip arthroplasty at 5-10 years.
      Methods: In total, 1592 hips (1473 subjects) were enrolled in a multi-center, non
      comparative, open-label study of the PINNACLE system: N = 896 metal-on
      polyethylene (MOP), N = 667 metal-on-metal (MOM), N = 27 ceramic-on-polyethylene,
      and N = 2 unknown articulation. Harris Hip Score, Short Form 36, Western Ontario
      and McMaster Universities Osteoarthritis Index, and radiographs were collected
      through 10 years. Kaplan-Meier device survivorship was estimated. Results: There
      were 41 revisions (23 MOP, 17 MOM, 1 ceramic-on-polyethylene) through 10 years:
      56.5% of MOP revisions were for instability and 41.2% of MOM revisions were for
      adverse local tissue reaction. Kaplan-Meier device survivorship (N with further
      follow-up) was 97.0% (N = 720) at 5 years and 94.7% (N = 77) at 10 years.
      Conclusions: Medium- to long-term survivorship estimates were similar or better
      than other studies and registries for the PINNACLE system. Level of Evidence:
      III.

PMID- 30186927
TI  - Letter to the editor on " Survivorship of a modular acetabular cup system: medium
      to long-term follow-up".

PMID- 30186926
TI  - Salvage of failed internal fixation of intertrochanteric hip fractures: clinical
      and functional outcomes of total hip arthroplasty versus hemiarthroplasty.
AB  - Background: Failed internal fixation of intertrochanteric (IT) hip fractures
      presents a significant challenge in the elderly, osteoporotic population.
      Conversion total hip arthroplasty (cTHA) and hemiarthroplasty (cHA) are both
      accepted salvage operations for failed IT fracture fixation, though limited
      clinical data exist regarding the optimal treatment between these procedures.
      Methods: A systematic review of 3 databases (PubMed, Cochrane, and Embase) was
      performed using the Preferred Reporting Items for Systematic Reviews and Meta
      Analyses (PRISMA) guidelines. Inclusion criteria were English-language studies
      that compared clinical or functional outcomes after failed fixation of IT
      fractures with total hip arthroplasty and hemiarthroplasty in adult subjects (>18
      years of age). Data regarding research design, surgical technique, and clinical
      or functional outcomes were obtained and analyzed from eligible studies using a
      Mantel-Haenszel random-effects analysis model. Results: Six studies with 188
      patients (100, total hip arthroplasty; 88, hemiarthroplasty) met inclusion and
      exclusion criteria. There was no significant difference between cTHA and cHA for
      postoperative dislocation, reoperation, infection, intraoperative fractures,
      postoperative fractures, or stem subsidence. The mean change in Harris Hip Scores
      was significantly higher (P < .001) in the cTHA group (47.5 +/- 4.9) than that in
      the cHA (38.9 +/- 7.2) group at minimum 14-month follow-up. Conclusions: Despite
      potential advantages of cTHA or cHA for failed IT fractures, there were no
      differences in complications between either of the salvage procedures. Our
      analysis found a slight advantage in functional outcomes (Harris Hip Score) for
      cTHA at a minimum 14-month follow-up. Our study suggests that cTHA and cHA are
      both effective salvage procedures. Additional prospective studies are warranted
      to further delineate outcomes after salvage arthroplasty performed for failed IT
      fracture fixation.

PMID- 30186928
TI  - Response to letter to the editor on "Survivorship of a modular acetabular cup
      system: medium- to long-term follow-up".

PMID- 30186929
TI  - Columnar-Lined Esophagus Develops via Wound Repair in a Surgical Model of Reflux
      Esophagitis.
AB  - Background & Aims: After esophagojejunostomy, rodents develop reflux esophagitis
      and a columnar-lined esophagus with features of Barrett's metaplasia. This rodent
      columnar-lined esophagus has been proposed to develop from cellular reprogramming
      of progenitor cells, but studies on early columnar-lined esophagus development
      are lacking. We performed a systematic, histologic, and immunophenotypic analysis
      of columnar-lined esophagus development in rats after esophagojejunostomy.
      Methods: At various times after esophagojejunostomy in 52 rats, the esophagus was
      removed and tissue sections were evaluated for type, location, and length of
      columnar lining. Molecular characteristics were evaluated by immunohistochemistry
      and immunofluorescence. Results: At week 2, ulceration was seen in esophageal
      squamous epithelium, starting distally at the esophagojejunostomy anastomosis. Re
      epithelialization of the distal ulcer segment occurred via proliferation and
      expansion of immature-appearing glands budding directly off jejunal crypts,
      characteristic of wound healing. The columnar-lined esophagus's immunoprofile was
      similar to jejunal crypt epithelium, and columnar-lined esophagus length
      increased significantly from 0.15 mm (+/-0.1 SEM) at 2 weeks to 5.22 mm (+/-0.37)
      at 32 weeks. Neoglands were found within esophageal ulcer beds, and spindle
      shaped cells expressing epithelial-mesenchymal transition markers were found at
      the columnar-lined esophagus's leading edge. Only proliferative squamous
      epithelium was found at the proximal ulcer border. Conclusions: After
      esophagojejunostomy in rats, metaplastic columnar-lined esophagus develops via a
      wound healing process that does not appear to involve cellular reprogramming of
      progenitor cells. This process involves EMT-associated migration of jejunal cells
      into the esophagus, where they likely have a competitive advantage over squamous
      cells in the setting of ongoing gastroesophageal reflux disease.

PMID- 30186930
TI  - Utilizing V-Y fasciocutaneous advancement flaps for vulvar reconstruction.
AB  - Objectives: We aimed to analyze the outcomes of patients who underwent vulvectomy
      with subsequent V-Y fasciocutaneous flap reconstruction. Methods: All medical
      records of all patients who underwent vulvectomies with V-Y fasciocutaneous flap
      reconstruction from January 2007 to June 2016 were retrospectively reviewed.
      Patient clinical and surgical data, demographics, and outcomes were abstracted.
      Results: Of the 27 patients, 42 flaps were transferred. A simple vulvectomy was
      performed in 8 (30%) patients, partial radical vulvectomy in 15 (56%), and
      radical vulvectomy in 4 (15%). The median area of defect was 30 cm2. Minor wound
      separations occurred in 9 patients (33%). Infectious complications occurred in 4
      patients (15%); this included urinary tract infections in 2 (50%), postoperative
      fevers in 2 (50%), and sepsis in 1 (25%) patient with a UTI. There were no
      instances of flap necrosis, wound dehiscence, or wound infections. Black race was
      more likely to be associated with an infectious complication with 3 (75%)
      patients, compared to white race with 1 (4%) patient (p < .01). The presence of
      diabetes was more likely to be associated with an infectious complication in 2
      (67%) patients, compared to 1 (4%) in non-diabetic patients (p < .01). No other
      significant association was found during analysis of demographics, medical
      comorbidities, vulvar pathology, or surgical factors affecting V-Y
      fasciocutaneous flap infectious complications or minor wound separations.
      Conclusions: The use of a V-Y fasciocutaneous advancement flap for vulvar
      reconstruction is safe and associated with mostly minor complications. Infectious
      complications were more frequently associated with diabetes, black race, and HIV.

PMID- 30186931
TI  - Delayed subclavian artery rupture secondary to a traumatic first rib fracture.

PMID- 30186932
TI  - Blunt trauma of unilateral intraperitoneal kidney: A case report.
AB  - The kidney is located and fixed with Gerota's fascia in the retroperitoneal space
      and is surrounded by a fat pad that acts as a shock absorber in the normal
      anatomy; however, the kidney becomes more vulnerable to external shock when it is
      located intraperitoneally. Bleeding from an injury may advance to hemoperitoneum
      and unstable hemodynamics may develop, requiring emergency surgery. Although
      various anatomical variations of the kidney have been reported, to our knowledge,
      an intraperitoneal kidney has never been reported previously except for one case
      in the world literature. This paper describes a successful nephrectomy of a
      unilateral intraperitoneal kidney in a 69-year-old woman who had grade IV
      laceration based on the renal injury scale of the American Association for the
      Surgery of Trauma with unstable hemodynamics after blunt trauma.

PMID- 30186933
TI  - Simultaneous false aneurysm and arterio-venous fistula in the presence of a
      single wound.
AB  - We describe a patient in whom a stab wound to the right supraclavicular fossa led
      to a subclavian artery false aneurysm and an arterio-venous fistula (AVF) between
      the right subclavian artery and the right internal jugular vein. The diagnosis
      was made clinically and with computerised tomographic angiography (CTA). Open
      vascular repair was successful. We postulate that this presentation was the
      result of the knife being inserted then partly withdrawn and reinserted at a
      different angle. This pattern of injury has been reported previously following
      central venous line insertion, but rarely following a stab injury.

PMID- 30186934
TI  - Taking the bull by the horns: Patient trampled by bull requiring surgical
      fixation of multiple rib fractures including rib 11.
AB  - Rib fractures are a serious problem in thoracic trauma resulting in high
      morbidity and mortality. Surgical stabilization in the management of rib
      fractures is gaining more popularity and recognition as outcomes continue to show
      positive results, however, there is still hesitancy among the trauma community to
      recommend this intervention. Although there still remains questions as to which
      patients to provide surgical stabilization to in the non-flail rib fracture
      patient population, surgical stabilization of rib fractures have been shown to be
      extremely beneficial in those patients with flail chest and should be strongly
      considered in this patient population, especially if they require ventilatory
      support. Here we present a 62-year-old female with severe chest wall deformity
      from 21 rib fractures after being trampled by a bull. This included a flail
      segment and a severely angulated 11th rib fracture piercing through the lung into
      the retroperitoneum. Furthermore, we also introduce a new technique for
      stabilization of rib fractures that are more posterior. Given the fact we
      surgically intervened early in our patient with severe chest wall trauma, she had
      a very favorable outcome, allowing her to be discharged from the hospital in a
      timely fashion with minimal overall morbidity.

PMID- 30186935
TI  - Disparities in individual health behaviors between medicaid expanding and non
      expanding states in the U.S.
AB  - Following the roll out of the Affordable Care Act, a significant amount of
      research has focused on health insurance coverage disadvantages experienced by
      those in states that chose not to expand Medicaid. This line of research has been
      used as a way to conceptualize potential disparities in future population health
      outcomes between states that did and did not expand Medicaid. While health
      insurance is certainly associated with health outcomes, health behaviors are
      equally, if not more, important. Therefore, to understand potential future
      population health outcomes - or lack thereof - this paper examines whether adults
      in states that did not expand Medicaid are also more likely to engage in health
      damaging behaviors (i.e. smoking, heavy drinking, physical inactivity, and
      overweight and obesity) than adults in states that expanded Medicaid. I find that
      those in states that did not expand Medicaid are more likely to be overweight and
      obese but are less likely to drink heavily compared to adults in states that did
      expand Medicaid. In part, higher rates of demographic and socioeconomic
      disadvantage explain higher rates of health damaging behaviors in states that did
      not expand Medicaid. This paper raises concerns about added long term
      consequences for population health and growing health disparities between states
      that did and did not expand Medicaid. Policy and practice implications of these
      findings are discussed.

PMID- 30186936
TI  - Mental health problems among economically disadvantaged adolescents in an
      increasingly unequal society: A Swedish study using repeated cross-sectional data
      from 1995 to 2011.
AB  - Increasing inequality in many societies highlights the importance of paying
      attention to differences in mental health between the economically disadvantaged
      adolescents and the non-disadvantaged adolescents. Also important is to
      understand how changing inequality in society over time influences adolescents'
      mental health at the population- and individual-level. The current study examined
      to what extent increased societal-level income inequality over time, individual
      level experiences of economic disadvantage and the cross-level interaction
      between the two explained Swedish adolescents' mental health problems from 1995
      to 2011. We used repeated cross-sectional data collected 6 times between 1995 and
      2011 in Sweden. Each time, approximately 2500 students in grade 9 completed a
      questionnaire during the spring semester. The adolescents provided self-report
      data on the frequency of their experiences of unaffordability of daily leisure
      activities (concert, movie, sports, and dance). They also reported their
      psychosomatic symptoms, which was used as a measure of mental health problems. We
      used the household equalised disposable income Gini coefficient as an indicator
      of societal income inequality. A real gross domestic product (GDP) per capita was
      controlled for in order to rule out potential effects of economic growth in the
      society over time. Multilevel regression analyses were conducted in which
      students were nested in years of investigations. Adolescents who experienced
      unaffordability of daily leisure activities reported more mental health problems.
      Societal income inequality was not directly associated with the adolescents'
      mental health. However, among girls the effects of experiences of unaffordability
      on mental health were stronger for all but one (sports) activities, and among
      boys for one activity (sports) when societal-level inequality was greater.
      Individual-level economic disadvantage are detrimental for adolescents' mental
      health, both directly and interactively with societal-level economic inequality.
      Some suggestions for practice and future studies are made for mental health among
      adolescents in societies where increasing inequality is observed.

PMID- 30186937
TI  - Oral anticoagulant use for stroke prevention in atrial fibrillation patients with
      difficult scenarios.
AB  - Atrial fibrillation (AF) has become the most prevalent arrhythmia and it will
      increase the risk of ischemic stroke, heart failure, mortality, sudden cardiac
      death, myocardial infarction, and dementia. Stroke prevention with oral
      anticoagulant is crucial for management of AF patients. Vitamin K antagonist,
      which inhibits the clotting factors II, VII, IX and X, has been recommended for
      stroke prevention for decades. Non-Vitamin K antagonist oral anticoagulants
      (NOACs), including dabigatran, rivaroxaban, apixaban and edoxaban are at least as
      effective as warfarin in reducing ischemic stroke with a lower rate of major
      bleeding. With the increasing prevalence of AF, prescription of the appropriate
      oral anticoagulants (OACs) according to patient's characteristics becomes a
      challenge. This review article aims to provide an overview of anticoagulant use
      in AF patients with difficult scenarios.

PMID- 30186939
TI  - Standing up for Subjectivity in the Assessment of Competencies.

PMID- 30186940
TI  - From HAM-Nat to the "Physikum" - Analysis of the study success parameters before
      and after the introduction of a science test in the approval procedure.
AB  - Background/Objectives: For the winter semester 2012/13, the Medical School of
      Otto-von-Guericke University Magdeburg introduced the HAM-Nat test (Hamburg
      Assessment Test for Medical Degrees - Natural Sciences Section) for the selection
      of its study applicants with the aim of improving the academic success of their
      students in the pre-clinical part which has a heavy emphasis on natural sciences.
      The study examines the extent to which the new University Selection Procedure
      (AdH) influences two criteria for measuring students' success, compliance with
      the standard period of study up until the first part of the medical state exam
      (M1) and its result. Methodology: A comparison of above-mentioned parameters for
      measuring student success for the matriculation years 2008-2011 (no HAM-Nat test,
      Pre-Matriculation) and those of the matriculation years 2012-2014 (Nat
      Matriculation), whose students have passed the HAM-Nat test in the selection
      process of the university. In addition, it was taken into account the number of
      course certificates gained within the standard time period. In the Nat
      Matriculation, the HAM-Nat results were merged with the associated M1 exam
      results. Results: The proportion of AdH students who were admitted to the
      Physikum (first part of the medical state exam (M1)) within the standard period
      of study only increased slightly in the period studied. Within the AdH group, 70%
      of the Pre-Matriculation group gained entry to the second phase of studies
      without delay, rising to 78% in the AdH-group of the Nat-Matriculation. For all
      admission groups taken together, the overall grades for the first section of the
      medical state exam 2010-2016 show a positive trend, regardless of the selection
      procedure. The proportion of correctly answered questions in the nationwide M1
      increased accordingly in the period studied. The better those matriculating had
      performed in the HAM-Nat test, the better their results were in the written and
      oral parts of the first part of the medical state exam. Conclusion: Although a
      significant proportion of students in the AdH group had obtained their place of
      study only on the basis of their test result and the score in the HAM-Nat test
      only weakly correlated with the school leaving grade (Abitur), the quantifiable
      study success parameters to date - in an albeit short observation period before
      and after introduction of the test - improved slightly. The number of Nat
      Matriculations is too low to be able to assess the effect of the HAM-Nat test
      bearing in mind natural fluctuations. Nevertheless, the HAM-Nat test as an
      instrument of selection also made it possible for candidates with originally
      insufficient Abitur grades to gain admission without negative effects on the
      study success of the AdH cohort.

PMID- 30186938
TI  - Cultural Competence and Global Health: Perspectives for Medical Education -
      Position paper of the GMA Committee on Cultural Competence and Global Health.
AB  - Introduction: Routine medical care in Germany, Austria and Switzerland is being
      increasingly impacted by the cultural and linguistic diversity of an ever more
      complex world. Both at home and as part of international student exchanges,
      medical students are confronted with different ways of thinking and acting in
      relation to health and disease. Despite an increasing number of courses on
      cultural competence and global health at German-speaking medical schools,
      systematic approaches are lacking on how to integrate this topic into medical
      curricula. Methodological approach: This paper is based on a structured consensus
      building process by a multidisciplinary committee composed of faculty and
      students. In a first step, a qualitative online survey was carried out in order
      to establish an inventory of definitions and concepts. After the second step, in
      which a literature search was conducted and definitions of global health and
      transcultural and intercultural competence were clarified, recommendations were
      formulated regarding content, teaching and institutional infrastructure. Based on
      small-group work and large-group discussions, different perspectives and critical
      issues were compiled using multiple feedback loops that served to ensure quality.
      Results: An inventory on the national and international level showed that great
      heterogeneity exists in regard to definitions, teaching strategies, teaching
      formats and faculty qualification. Definitions and central aspects considered
      essential to medical education were thus established for the use of the terms
      "cultural competence" and "global health". Recommendations are given for
      implementation, ranging from practical realization to qualification of teaching
      staff and education research. Outlook: High-quality healthcare as a goal calls
      for the systematic internationalization of undergraduate medical education. In
      addition to offering specific courses on cultural competence and global health,
      synergies would be created through the integration of cultural competence and
      global health content into the curricula of already existing subject areas. The
      NKLM (the national competence-based catalogue of learning objectives for
      undergraduate medical education) would serve as a basis for this.

PMID- 30186941
TI  - Risks and errors in medicine. Concept and evaluation of an optional study module
      with integrated teaching of ethical, legal and communicative competencies.
AB  - Objective: The presentation and discussion of the content, methodology and
      evaluation results of a course on "Risks and Errors in Medical Science", adopting
      an integrated approach for the teaching of ethical, legal and communicative
      aspects. Method: Written, structured evaluation using the adapted evaluation form
      "Evasys" as well as open questions on positive and negative aspects of the course
      and assessment of the effects thereof from the participants' viewpoint. The free
      text responses are evaluated according to the principles of qualitative content
      analysis. Results: Thirty-two from thirty-six participants (88.9%) evaluated the
      course in written form. The value for the global assessment of the course is a
      1.7 (1=very good, 6=unsatisfactory). The self-assessed learning success was
      evaluated with a 1.9. In the qualitative analysis of the free text answers the
      case orientated teaching, the use of simulated patients as well as the legal
      content and the ethical models of the doctor-patient relationship were evaluated
      positively. Negative aspects of the course were, among other things, the
      weighting of the contents and the limited amount of time allotted. Impacts and
      changes were identified by the students in terms of knowledge of legal aspects,
      reflection on their own action and the training and further development of
      communication aptitudes. The students saw the relevance of the course for their
      studies especially in the supplement to the compulsory curriculum as well as in
      the significance of the content of medical law. Conclusions: The experience of
      the authors and the written evaluation results show that the concept of
      integrated teaching can be implemented in medical studies and that it is
      predominantly evaluated positively. The primary challenges are the weighting of
      the different contents and methods as well as the comparatively high demand for
      coordination among representatives of various disciplines.

PMID- 30186942
TI  - Development and initial Experience of an online Exchange Platform on Sex and
      Gender Aspects in Medicine: "GenderMed-Wiki".
AB  - Goal: Knowledge about sex/gender aspects in medicine is often lacking, even
      though this serves as base for individualized patient-centered care. Thus we
      developed an online exchange platform on sex and gender aspects in medicine:
      "GenderMed-Wiki" [www.gendermed-wiki.de]. This was funded by the German Federal
      Ministry of Education and Research (BMBF; FKZ: 01FP1506). Our goal is to
      facilitate the integration of sex and gender in all areas of medicine. Therefore
      we evaluated if "GenderMed-Wiki" is suitable to provide knowledge on sex and
      gender aspects in medicine adequately. Methods: Qualitative evaluation of
      "GenderMed-Wiki" was done 6 months after project start by 4 focus groups with a
      total of 30 participants (students, lecturers, physicians, and the public). The
      discussions in each focus group were minuted, requirements pooled and new
      categories derived inductively. After further optimization of the platform a
      quantitative survey was done by an online questionnaire (SoSci Survey). 149
      students of the medical faculties of Muenster and Duisburg-Essen (as well as
      students of dentistry from the medical faculty of Muenster) participated (return
      rate of 3.3%). Evaluation of the content of the articles was done by assessing
      three professional articles: Sex/gender and medicine (both study courses medicine
      and dentistry), depression (medicine only) and periodontitis (dentistry only).
      The results were reported in relative and absolute frequencies and associations
      were assessed by Chi-Quadrat-tests. Results: Four categories which needed further
      optimization were deducted from the responses given by our focus groups prior to
      evaluation: aspects related to content, technical requirements, usability of the
      platform and legal challenges. Most of the students found "GenderMed-Wiki" to be
      informative, however they didn't think it to be relevant for their current
      studies. In contrast, many thought that the platform may be useful when working
      as physicians. Students who reported that topics related to sex and gender were
      not of importance to them, evaluated the platform more neutrally and answered
      questions related to sex/gender in depression more often incorrectly.
      Conclusions: Focus groups are a useful approach to identify necessary changes in
      projects in a systematic way. After further optimizations, "GenderMed-Wiki" seems
      to be suitable to facilitate the integration of sex/gender into medical
      teachings. It is of importance, however, to change the attitude of students
      towards sex/gender sensitive medicine (e.g. by integration into the medical
      curriculum), since this influences strongly how this platform is perceived and
      how someone deals with its contents.

PMID- 30186943
TI  - Heidelberger Interprofessionelle Ausbildungsstation (HIPSTA): a practice- and
      theory-guided approach to development and implementation of Germany's first
      interprofessional training ward.
AB  - Background: Deficits in care and impaired patient-safety have been linked to
      inefficient interprofessional collaborative practice. Interprofessional training
      wards (IPTW) are an interprofessional educational intervention which aim to
      enable students and trainees from different health professions to work self
      responsibly in order to manage the medical treatment and rehabilitation of real
      life patients together as an interprofessional team. We aimed to develop and
      implement Germany's first IPTW at the department of Surgery at Heidelberg
      University Hospital. Methods: The Kern cycle was used to develop an ITPW
      curriculum. Practical as well as theoretical considerations guided the design of
      the IPTW. Common project management tools including blueprinting and RASCI
      (Responsibility, Approval, Support, Consultation, Information) matrix were
      applied. Results: Since April 2017, 7 cohorts of students and trainees have had
      four-week long placements on HIPSTA. They run the IPTW in early and late shifts.
      Nursing and medical facilitators are supporting the IP team as needed. Learning
      objectives are operationalized as EPAs (entrustable professional activities) and
      interprofessional learning goals. Since initiation only minor modifications to
      the curriculum have been necessary and satisfaction of students/trainees,
      facilitators and patients is high. Conclusion: IPTWs can be established and run
      in the German health care system even in a complex clinical setting. The early
      involvement of all professions in a steering group seems to be key to success.
      Nursing and medical facilitators are of utmost importance for daily routine. The
      experiences outlined here could help others aiming to implement IPTWs at their
      sites. IPTWs might address a number of hitherto unaddressed educational needs.
      Trial registration: Not applicable.

PMID- 30186944
TI  - Teaching load - a barrier to digitalisation in higher education? A position paper
      on the framework surrounding higher education medical teaching in the digital age
      using Bavaria, Germany as an example.
AB  - This position paper describes the legal framework requirements when crediting
      digital teaching formats towards the teaching load in higher education medical
      teaching, as exemplified by the Federal State of Bavaria in Germany. It reveals
      the need for precise rules adapted to the advances in technology, if the process
      of digitalisation in higher education (HE) is not to come to a halt. If HE
      institutions are to act as centres of innovation with respect to the
      implementation of digital teaching and learning formats, then structural and
      strategic positioning with regard to e- and blended learning above all is called
      for in addition to financial resources, as well as the distribution and
      sustainable incorporation of digital offerings in faculties and HE institutions.
      There is a great deal of insecurity however with respect to the legal framework
      requirements and how best to count digital teaching towards one's own teaching
      load. This results to some extent from the complexity of current laws and
      regulations partially overtaken by didactic and methodological changes in
      education, with decentralised educational federalism only adding to the
      complexity. Bearing in mind teaching and learning formats that are undergoing
      change or have already been transformed, ways of adapting the (legal) framework
      to the digital shift need to be found, last but not least in order to offer
      enthusiastic teaching staff incentives to develop and expand digital formats.

PMID- 30186945
TI  - Just watching is not enough: Fostering simulation-based learning with
      collaboration scripts.
AB  - Aims: In addition to medical facts, medical students participating in simulation
      based training are supposed to acquire general knowledge, e.g. heuristics to cope
      with critical incidents. While active participation is considered a major benefit
      of this kind of training, a large portion of students' time is often spent
      observing peers acting in the simulator. Thus, we instructionally supported
      learners with a collaboration script (i.e., a set of scaffolds that distribute
      roles and activities among learners in group learning situations) during
      observational phases of a simulation-based training. Our script was designed to
      help learners focus on heuristics and to facilitate more (inter-)active
      participation. We hypothesised that scripted learners would benefit from the
      instructional support with respect to individual and collaborative learning
      processes as well as individual learning outcomes. Methods: Thirty-four medical
      students in their 7th to 12th semester participated in this field study with
      control group design. The independent variable was the collaboration script
      (with/without). Four voluntary emergency courses with a full-scale simulator were
      examined. The acquisition of skills related to Crisis Resource Management (CRM)
      heuristics was one of the learning goals of these courses. The collaboration
      script induced learners to perform specific activities during and after each
      observational phase of the training. Further, the script sequenced the order of
      activities and assigned roles to the learners. Learning processes were measured
      on an individual level (by means of notes taken by learners during observational
      phases) and on a collaborative level (by means of learners' comments). Learning
      outcomes were measured with pre- and post-self-assessment of CRM skills and a
      brief video-based CRM skills test at the end of the course. Results: The
      collaboration script had the expected positive effect on individual and
      collaborative learning processes, leading to an increased focus on heuristic
      strategies and increased collaborative activity of scripted learners. There was
      no evidence that the experimental conditions differed regarding the objective
      measure of individual learning outcomes. However, self-assessment data revealed
      that students in the control condition perceived a higher improvement of CRM
      skills throughout the course. We suggest that our script might have helped
      learners adjust an illusion of their own competency - such an illusion may have
      appeared in the control group as a result of processing fluency. Conclusions:
      Findings suggest that simulation-based training in medical education can be
      enhanced with additional instructional support in the form of collaboration
      scripts designed to turn observational course phases into more active and better
      focused learning experiences.

PMID- 30186946
TI  - Self-evaluation of present clinical skills by medical students in the years 3 to
      6 - a pilot study in four European countries.
AB  - Background: Clinical training concepts of medical students differ in the various
      European countries. The goal of this paper is to study the differences at the
      beginning of medical practice in specific clinical skills on an international
      level. Methods: The data were collected by a publically accessible online
      questionnaire online from February to June 2010. The participants in the study
      were recruited through the official letter sent by deaneries and student
      organisations. Two thousand nine hundred and seven medical students participated
      in the online survey. From study years 1 to 6, 2406 valid data records (67.3
      percent female; 32.7 percent male) from four different European countries were
      sent. The skills in the questionnaire included patient consultation and
      anamnesis, physical examination, auscultation, gypsum and bandage dressing,
      suture techniques, venepuncture, and laying of indwelling catheters. Results: One
      thousand six hundred and twenty-nine data records of medical students in their
      training years 3 to 6 were assessed. The average age of the students was 24.7
      years. On a scale from 1 to 10, the average satisfaction of the students with
      their medical faculty was 6.47 (+/-2.07); the assessment of the preparation for
      the clinical activities was 4.72 (+/-2.13). By comparison, British students
      indicated most satisfaction with their training (6.70+/-1.85). With respect to
      the clinical skills, the students interviewed felt safest in patient consultation
      and anamnesis (7.63+/-2.13) followed by blood sampling (7.46+/-2.29). The topics
      of surgical suturing techniques (4.40+/-2.81) and the gypsum and bandaging
      techniques (2.63+/-2.23) were taught worst subjectively. Discussion: The training
      of medical students in basic clinical skills is an essential part of the studies.
      This study was able to demonstrate that the subjective trust of medical students
      in their personal skills positively correlated with the satisfaction with their
      own university. The results pointed out that future curricula of universities
      could profit from an increased focus on clinical skills.

PMID- 30186947
TI  - Physicians' roles in competency-based teaching: Do students recognize them?
AB  - Introduction: Imparting the concept of physician's roles with the help of new
      teaching formats is becoming increasingly important in medical education. The
      "ambulatory care simulation" was developed at the Medical Faculty Mannheim as a
      format to teach the roles of "medical expert," "communicator", "health advocate",
      "manager", "team member" and "professional" in the practical year. During the
      "ambulatory care simulation", students work through case scenarios with simulated
      patients focusing on the physician's roles and subsequently discussing and
      reflecting on their experiences. Several measures are designated to ensure that
      each role is covered by the new teaching format. The present study investigates
      whether the physician's roles are actually addressed during the "ambulatory care
      simulation" and whether the competency-based learning objectives are recognized
      by the students. Methods: All participants in 12 of the 38 obligatory "ambulatory
      care simulations" signed informed consents to be filmed during the "ambulatory
      care simulation". These videos were categorized using previously defined
      observation criteria. A total of 211 out of 224 students completed and handed in
      a one-minute paper at the end of the "ambulatory care simulation". The answers to
      the question, "What have you learned?" have been assigned to competency-based
      learning objectives. Results: Although instructors and students adhered to the
      guidelines in the recorded "ambulatory care simulations", the most frequently
      addressed roles were "medical expert" and "communicator." Two-thirds of the
      participants indicate learning outcomes that do not correspond to the previously
      defined learning objectives of the "ambulatory care simulation". Discussion: To
      ensure a thorough understanding and long-lasting appreciation of the physician's
      roles, longitudinal integration of teaching interventions into the curriculum is
      to be favored over single teaching units. Instructors need intensive preparation
      for the unfamiliar construct of physician's roles. The learning objectives must
      also be made more transparent. Conclusion: Especially complex teaching formats
      need to be evaluated for success if they are to achieve their aims. Formative
      evaluations enable verification of whether the learning objectives are addressed,
      recognized and, finally, achieved.

PMID- 30186948
TI  - "Heidelberg Standard Examination" - Final year students' experiences with a
      handbook and instructional videos to improve medical competence in conducting
      physical examinations.
AB  - Background: The physical examination (PE) of patients is a core competence in
      almost all medical disciplines. The teaching materials "Heidelberger Standard
      Examination", consisting of a handbook and accompanying videos, were developed
      with the objective of providing medical students with an innovative faculty-wide
      teaching and examination standard to sustainably advance students' PE competences
      during medical training. Methods: In a "mixed-method approach" comprising both
      quantitative and qualitative measures, our study examined Heidelberg University
      Hospital final year (FY) medical students' use and evaluation of the individual
      teaching material components. Therefore, 92 FY students completed quantitative
      evaluation measures and ten FY students took part in individual 30-minute semi
      structured interviews. Results: Of the sample of n=77 students, who had completed
      the clinical part of their studies at Heidelberg University Hospital, 97.4%
      (n=75) had used the handbook and 35.0% (n=27) the accompanying videos. The
      teaching materials were evaluated via the common German six-point school grading
      system with an average mark of 1.35+/-0.5 for the handbook and a mark of 2.15+/
      1.0 for the accompanying videos. Further, our results show that FY students
      especially valued the "Heidelberg Standard Examination" handbook as a guide and
      general reference work and felt the materials improved their self-perceived PE
      competence. Although FY students saw the accompanying video material as helpful,
      it was less frequently used, indicating further development potential. Overall,
      results reveal that FY students perceive the "Heidelberg Standard Examination"
      teaching program to contribute to the improvement of the quality of their PE
      training.

PMID- 30186949
TI  - Successful completion of clinical electives - Identification of significant
      factors of influence on self-organized learning during clinical electives with
      student focus groups.
AB  - Background: The Medical Licensure Act prescribes a total of four months of
      clinical electives in which the medical students are to work in a self-organized
      manner in outpatient and inpatient care. Since no specific learning objectives or
      learning content are given and students come into contact with different
      structures of outpatient and inpatient care, the learning success in a clinical
      elective is often rather random. In order to make self-organized learning (SOL)
      in clinical electives as effective as possible, we identified factors in the area
      of inpatient care that have an influence on SOL and thus the learning success
      during a clinical elective. Methods: To investigate this question a qualitative
      and explorative approach was chosen. In 2015, a total of 21 students from
      semester 1 to 11 participated in six semi-structured focus group discussions at
      Hamburg Medical Faculty. In these, the students were asked about their
      experiences and expectations with regard to SOL in clinical electives. The
      interviews were transcribed literally and analyzed using Grounded Theory in
      parallel to further data collection. Results: Three main categories were
      identified, which had an impact on SOL in clinical electives, each with two sub
      categories: People (elective students and physicians), learning itself (learning
      content and learning process) and the framework (local conditions and
      organizational structure). For example, elective students exhibiting openness and
      self-initiative as well as a good working atmosphere and few hierarchical
      structures were conducive to SOL, while shyness and lack of integration into the
      ward's medical team inhibited SOL. A mentor formally assigned to the student can
      promote SOL through guidance, supervision and the transfer of responsibility.
      Continuous feedback from mentors or peers promotes SOL. Framework conditions,
      such as a smooth administrative organization, also affect SOL, but elective
      students have limited influence over these. Conclusion: The creation of suitable
      framework conditions and considering the needs of the people involved in clinical
      electives and the requirements of learning itself are necessary steps in order to
      enable successful SOL during clinical electives. Suitable framework conditions
      could be compiled and widely disseminated on an empirical basis. Training for
      teachers and elective students on various aspects of clinical electives, from
      professional behavior to practical skills, could be a suitable preparatory
      measure to promote SOL in clinical electives and contribute to a better learning
      success of the elective students.

PMID- 30186950
TI  - Simulation centres in German hospitals and their organisational aspects: Expert
      survey on drivers and obstacles.
AB  - Background: Simulation trainings offer the opportunity to replicate parts of or
      entire processes of medical care in a controlled environment. Some hospitals
      operate simulation centres dedicated to training their staff. Which
      organisational factors support or impede the implementation of such units in
      hospitals? Methods: In an exploratory survey experts and decision makers in
      German hospitals were interviewed. The answers were evaluated qualitatively in
      order to identify patterns in argumentation. Among the eleven participants were
      practitioners heading simulation centres (n=4), managers or executives in charge
      of finances (n=2), medical directors or head physicians with disciplinary
      responsibility for medical personnel (n=3), and researchers who deal with
      simulation trainings in medicine (n=2). The interview partners were guaranteed
      confidentiality in order to allow for them to speak freely about the obstacles
      and weaknesses in their respective organisations. Results: The interviewees
      showed a very heterogeneous picture of the simulation trainings in their
      respective hospitals in terms of content as well as target groups. Asked about
      purpose and benefit of simulation centres, subgroups of the interviewees gave
      various arguments. Financing is comprised of subsidies, fees from external
      participants, and of vocational training budgets. Several obstacles for the
      implementation were mentioned such as insufficient error culture, deficient
      interaction of quality and risk management, high equipment costs, or staffing
      levels that are too low to schedule entire teams for vocational trainings.
      Conclusions: Patterns in argumentation could be identified that support the
      implementation and operation of simulation centres in hospitals. Yet strikingly
      enough there were no coherent arguments i.e. there was no uniform reasoning of
      aim and purpose of simulation centres. Furthermore, the survey indicated the need
      to approach quality- and risk management more holistically wherefore simulation
      centres could offer laboratory environments. All in all, the survey indicates
      that the assessment of success and economic benefits of simulation centres
      haven't yet been examined thoroughly.

PMID- 30186951
TI  - How case representations of medical students change during case processing -
      Results of a qualitative study.
AB  - Objective: Representations are mental summaries of a clinical case and help in
      understanding a clinical problem. However, it is still largely unknown which
      clinical information medical students include in their case representations. In
      this study, therefore, the structure and quality of students' case
      representations were examined to better understand the diagnostic process and its
      relationship to diagnostic accuracy. What information do medical students include
      in their representations and is there an association between this information and
      the diagnostic accuracy? Method: 43 medical students in the fourth and fifth
      clinical year worked on four clinical cases. During the diagnostic process, they
      were asked three times per case to write a case representation. 516
      representations were qualitatively evaluated using a content-based coding scheme.
      An analysis was made of the nature and composition of the clinical information.
      In addition, the association between the general representation structure and the
      correct case solution was examined. Results: At the beginning, students include
      most of the clinical information in their representation (66%), but as the case
      progresses, they begin to select the information offered (2nd representation 42%,
      3rd representation 38%). The length of the representation (number of words) does
      not correlate with the correct case solution (r=-0.08-0.31). The representations
      do not depend on the case difficulty but have a significant individual component:
      the representations written by a student are formally very similar in all four
      cases (r=0.60-0.86). Conclusion: Medical students can select the relevant
      clinical information and include it in their case representations. Lack of
      representation does not seem to be a reason for misdiagnosis; Students' deficits
      in diagnosis are more likely due to knowledge gaps.

PMID- 30186952
TI  - How can General Practice be incorporated longitudinally in medical studies?
      Students' views on the development of a new rural health program.
AB  - Aim: Participation of medical students in the conceptual development of targeted
      and attractive teaching content for rural areas. Method: A questionnaire was
      developed to gather information on students' views of their current medical
      studies, career interests, and what requirements should be met by an optional
      rural health program in general practice. By means of an online survey in summer
      2015, all medical students from the fourth preclinical semester onwards (n=2,150)
      at Goethe University Frankfurt were surveyed on one occasion. Statistical
      analysis was mainly descriptive. Personal attitudes towards a career as a family
      practitioner were examined for statistical significance. Further information was
      gathered on whether a measurable correlation exists between personal background
      and desired work location. Results: Of the 2,150 students that were contacted,
      617 participated in the survey (response rate=28.7%). The results covered a wide
      range of ideas and recommendations and were representative both of medical
      students with a positive attitude toward general practice, as well as those that
      were rather critical of teaching in general practice. The students expected the
      planned health program to be of strong practical relevance and to acquaint them
      with the administrative and economic aspects of running a practice. Conclusions:
      By including the target group in the development process, it was possible to
      tailor the health program to meet the needs of future participants more
      precisely. Student participation can also be expected to result in greater
      acceptance of the program. The results on teaching content may also provide other
      medical faculties with orientation when developing comparable programs.

PMID- 30186953
TI  - Digital Teaching and Digital Medicine: A national initiative is needed.
AB  - The advancing digitization of the healthcare system requires that in the future
      digital skills should be communicated to students much more. In addition, digital
      teaching and learning technologies should be used wherever they offer real
      benefits over other training scenarios. To meet these challenges, it needs a
      national initiative "Medical Education in the Digital Age", which should be led
      by the Society for Medical Education and the German Association for Medical
      Informatics, Biometry and Epidemiology.

PMID- 30186954
TI  - Report and Recommendations of the Association of Pathology Chairs' Autopsy
      Working Group.
AB  - Autopsy has been a foundation of pathology training for many years, but hospital
      autopsy rates are notoriously low. At the 2014 meeting of the Association of
      Pathology Chairs, some pathologists suggested removing autopsy from the training
      curriculum of pathology residents to provide additional months for training in
      newer disciplines, such as molecular genetics and informatics. At the same time,
      the American Board of Pathology received complaints that newly hired pathologists
      recently certified in anatomic pathology are unable to perform an autopsy when
      called upon to do so. In response to a call to abolish autopsy from pathology
      training on the one hand and for more rigorous autopsy training on the other, the
      Association of Pathology Chairs formed the Autopsy Working Group to examine the
      role of autopsy in pathology residency training. After 2 years of research and
      deliberation, the Autopsy Working Group recommends the following:Autopsy should
      remain a component of anatomic pathology training.A training program must have an
      autopsy service director with defined responsibilities, including accountability
      to the program director to record every autopsy performed by every
      resident.Specific entrustable activities should be defined that a resident must
      master in order to be deemed competent in autopsy practice, as well as criteria
      for gaining the trust to perform the tasks without direct supervision.Technical
      standardization of autopsy performance and reporting must be improved.The current
      minimum number of 50 autopsies should not be reduced until the changes
      recommended above have been implemented.

PMID- 30186955
TI  - Mucosal injury following short-term tracheal intubation: A novel animal model and
      composite tracheal injury score.
AB  - Objectives: Postintubation laryngotracheal injury is common. Assessment of
      histopathological changes currently requires animal models. We set about
      developing a viable, resource effective animal model to study these effects and
      to develop a detailed tissue injury score. Methods: Six pigs were anesthetized
      using a standard regimen. We intubated the tracheas using a standard endotracheal
      tube modified to include optical sensors. Animals were anesthetized for a
      duration of two to four hours, and their lungs were ventilated using a normoxic
      gas mixture. Following euthanasia, the tracheas were removed and underwent
      histological assessment by two independent veterinary pathologists. The
      histological lesions, including controls, were described and quantified, and two
      pathologists classified tissues according to a novel injury score. Results: Mean
      duration of tracheal intubation was 191 minutes (SD +/- 41.6). In all except one
      animal, cuff pressures were maintained in the range of 25-45 cmH20.
      Histopathological findings in all study animals showed more extensive changes
      than previously described with short-term intubation. Changes were seen in all
      mucosal layers consistent with acute, suppurative, and ulcerative tracheitis. The
      range of scores of the developed composite scoring system among the animals was
      wider than in earlier descriptions. There was a high percentage of agreement
      between both pathologists. Conclusions: We have described a novel tracheal injury
      score to assess pathological changes following short term intubation in a viable
      animal model. The scoring system distinguished between the test animals as well
      as controls and may be appropriate for continuing study of intubation injury.
      Level of Evidence: 3.

PMID- 30186957
TI  - Hemorrhage of MRI and Immunohistochemical Panels Distinguish Secretory Carcinoma
      From Acinic Cell Carcinoma.
AB  - Objectives: Secretory carcinoma (SC, mammary analogue secretory carcinoma) is a
      salivary gland tumor with ETV6-NTRK3 gene fusion, and its differential diagnosis
      includes acinic cell carcinoma (ACC). As hemorrhage is often seen in SC, we
      hypothesized that magnetic resonance imaging (MRI) and immunohistochemical
      analyses could distinguish SC from ACC. Study Design: Retrospective study.
      Methods: We used ETV6-NTRK3 gene fusion analyses to reclassify 19 parotid gland
      tumors that had previously been diagnosed as SC or ACC, and then investigated
      hemorrhage in both hematoxylin-eosin (H&E)-stained sections and MRIs, and
      immunohistochemical expression of S-100, mammaglobin, DOG1, and alpha-amylase.
      Results: The 19 tumors were genetically reclassified into 11 (58%) SC and 8 (42%)
      ACC. Combined S-100 and mammaglobin were specific for SC; whereas DOG1 was
      specific for ACC, and alpha-amylase was expressed only in 4 ACC cases (50%). H&E
      staining showed hemorrhage with hemosiderin deposition in all SC cases, and T2
      weighted MRI showed hypointense areas in all investigated SC cases, but not in
      ACC. Conclusion: Hemorrhage with hemosiderin deposition is frequently present in
      SC, and hemorrhage findings in MRI and an immunohistochemical panels for S-100,
      mammaglobin and DOG1 can distinguish SC from ACC. Level of Evidence: 3b.

PMID- 30186956
TI  - Detection of Second Primary Malignancies of the Esophagus and Hypophraynx in Oral
      Squamous Cell Carcinoma Patients.
AB  - Objective: To assess the usefulness of modified esophagogastroduodenoscopy (EGD)
      for the detection of second primary malignancies of the esophagus or hypopharynx
      in patients with oral squamous cell carcinoma and determine the association
      between the oral lesion subsite and esophageal or hypopharyngeal lesion
      occurrence. Study Design: Retrospective review. Methods: In total, 166 patients
      with oral squamous cell carcinoma without any established symptoms of esophageal
      or hypopharyngeal squamous cell carcinoma underwent modified EGD based on the
      Valsalva maneuver and U-turn method, image-enhanced endoscopy, and
      chromoendoscopy using Lugol's iodine for diagnosis. All suspected lesions were
      biopsied to determine the clinical stages and duplication rates. Odds ratios for
      the occurrence of duplicate lesions according to the oral lesion subsite were
      determined. Results: In total, 37 esophageal and 16 hypopharyngeal lesions were
      detected. According to the Union for International Cancer Control/American Joint
      Committee on Cancer classification (2009), 75.7% and 5.4% esophageal lesions were
      classified as stage IA and IB, respectively, and 50% and 18.8% hypopharyngeal
      lesions as stage II and stage I, respectively. Approximately 59.1% and 50%
      esophageal and hypopharyngeal lesions, respectively, were successfully treated by
      endoscopic resection. Oral lesions involving the floor of the mouth were more
      frequently accompanied by second primary malignancies of the esophagus or
      hypopharynx. Conclusions: Modified EGD is an effective noninvasive technique for
      early diagnosis and treatment of second primary malignancies of the esophagus and
      hypopharynx in patients with oral squamous cell carcinoma. In particular,
      patients with floor of the mouth lesions need close monitoring for hypopharyngeal
      and esophageal lesions. Level of Evidence: 3b.

PMID- 30186958
TI  - Treatment Patterns in Veterans with Laryngeal and Oropharyngeal Cancer and Impact
      on Survival.
AB  - Objectives: Veterans with laryngeal and oropharyngeal cancer remain an
      understudied patient population despite a high incidence of disease and decreased
      survival compared to the general population. Our objective was to evaluate
      treatment patterns for laryngeal and oropharyngeal cancer in patients treated at
      one of the Veterans Health Administration's busiest cancer centers in order to
      generate some basic benchmarks for treatment delivery in the veteran population.
      Methods: We reviewed 338 patients treated at the Michael E. DeBakey Veterans
      Affairs Medical Center between 2000 and 2012. Results: Oropharyngeal site and
      advanced age were associated with worse overall and disease-free survival.
      Treatment periods (mean) were as follows: 1) referral-diagnosis, 26 days; 2)
      diagnosis-surgery, 29 days; and 3) diagnosis-radiation, 58 days. Adjuvant
      radiation was initiated within 6 weeks of surgery in 42% of patients and 68% of
      patients had a total treatment package time <=100 days. Time from diagnosis to
      treatment initiation, surgery to adjuvant radiation interval and total treatment
      package time did not impact survival. Conclusions: This study establishes basic
      benchmarks for laryngeal and oropharyngeal cancer treatment delivery in veterans.
      Additional efforts are warranted to improve consistency and provide treatment in
      line with NCCN recommendations and literature consensus. Level of Evidence: 2b.

PMID- 30186959
TI  - Comparison of PI3K Pathway in HPV-Associated Oropharyngeal Cancer With and
      Without Tobacco Exposure.
AB  - Objectives: The aim of the study was to evaluate whether HPV associated OPSCC
      with tobacco exposure follows a different carcinogenic pathway compared to HPV
      associated OPSCC without tobacco exposure and to investigate its prognostic
      significance. The question was addressed with focus on components of the PI3K
      pathway. Methods: 184 patients with newly diagnosed OPSCC treated with curative
      intent were consecutively enrolled. The expression level of p16, p53, PI3K, mTOR,
      and PTEN was assessed by immunohistochemistry and analyzed in relation to the
      risk factors HPV status and tobacco exposure. Results: 94 of 184 (51%) patients
      were p16 positive, p53 overexpression was detected in 48 of 184 (26%) cases. PI3K
      overexpression with 70 of 184 (38%) cases was significantly higher in p16
      positive tumors. mTOR overexpression was present in 90 of 184 (49%) cases and
      significantly higher in p16 negative tumors. PTEN loss was found in 42 of 184
      (23%) cases without association to p16 expression. p16 positive OPSCC showed
      lower rates of p53 expression and mTOR expression as well as higher rates of PI3K
      expression irrespective of tobacco exposure. Survival analysis showed a distinct
      intermediate survival rate of p16 positive smokers. The markers PI3K, mTOR, and
      PTEN did not have a significant impact on survival. Conclusion: HPV associated
      OPSCC with tobacco exposure follows the same expression level of the PI3K pathway
      as HPV associated OPSCC without tobacco exposure. The impaired survival rate of
      the intermediate risk group cannot be explained by different expression patterns
      of PI3K, mTOR, and PTEN. Level of Evidence: 2b.

PMID- 30186960
TI  - Is There a Difference in Staging and Treatment of Head and Neck Squamous Cell
      Tumors Between Tertiary Care and Community-Based Institutions?
AB  - Objective: To characterize the differences in the staging and treatment of
      patients with head and neck squamous cell carcinoma between a tertiary care
      center and community-based practices. Methods: This study is a retrospective
      chart review of 943 adult patients with head and neck squamous cell cancer
      presenting to a tertiary care center between 2008 and 2014 as part of the
      University of Michigan Head and Neck Cancer Specialized Program of Research
      Excellence (UM HN-SPORE) database. Demographic information, diagnostic testing,
      staging information, and treatment recommendations were recorded. Results: Of 943
      patients reviewed, 159 had documentation of tumor stage that was assigned by the
      community-based practice. Of these, 53% had a tumor staging change made at the
      tertiary care center, with 43% of patients upstaged and 10% of patients
      downstaged. Fifty-one percent received different treatment than had previously
      been offered at the community-based practice, although only 31% of these patients
      had a change in tumor staging. Conclusion: Over half of patients with head and
      neck squamous cell carcinoma who are evaluated at a tertiary care center after
      the initial evaluation at a community-based practice have their tumors staged
      differently, with the majority upstaged. A significant number of these patients
      also received different treatment than was initially offered at the referring
      practice. Future studies are required to determine whether these differences have
      an effect on tumor recurrence and patient survival rates. Level of Evidence: 2c
      (Outcomes Research).

PMID- 30186962
TI  - Cognitive Functions in Adult Cochlear Implant Users, Cochlear Implant Candidates,
      and Normal-Hearing Listeners.
AB  - Objectives: Increasing evidence suggests that hearing loss may be linked to
      cognitive decline, and that cochlear implantation may lead to improvements in
      cognition. The goal of this study was to examine the effects of severe-to
      profound hearing loss and cochlear implantation in post-lingually deafened
      adults, compared with age-matched normal-hearing (NH) peers. Participants were
      tested on several non-auditory measures of cognition: working memory (WM) (digit
      span, object span, symbol span), non-verbal reasoning (Raven's progressive
      matrices), information-processing speed and inhibitory control (Stroop test),
      speed of phonological and lexical access (Test of Word Reading Efficiency), and
      verbal learning and memory (California Verbal Learning Test). Demographic
      measures were also collected. Methods: Cohort study at tertiary neurotology
      center. Forty-three post-lingually deafened experienced CI users, 19 post
      lingually deafened CI candidates, and 40 age-matched NH controls with no
      cognitive impairment were enrolled. Comparisons among the groups on the cognitive
      measures were performed. Results: Adult CI users and CI candidates demonstrated
      worse (or a trend towards worse) performance as compared with NH peers on non
      verbal reasoning, information-processing speed, speed of lexical access, and
      verbal learning and memory. However, after controlling for gender, socioeconomic
      status (SES), and vocabulary knowledge among groups, some of these differences
      were no longer significant. Similarly, large differences were not found in most
      cognitive abilities between experienced CI users and CI candidates. Conclusions:
      Adult CI users, CI candidates, and NH peers generally demonstrated equivalent non
      auditory cognitive abilities, after controlling for gender, SES, and vocabulary
      knowledge. These findings provide support for a link between cognitive decline
      and hearing loss, but this association may be partly attributable to group
      differences in SES and vocabulary knowledge. Level of Evidence: 2b.

PMID- 30186961
TI  - A Resuscitation Option for Upper Airway Occlusion Based on Bolus Transtracheal
      Lung Inflation.
AB  - Background: Acute laryngospasm sufficient to cause obstructive apnea is a medical
      emergency that can be difficult to manage within the very short time available
      for establishing an airway. We have presented substantial evidence that
      laryngospasm-based obstructive apnea is the cause of sudden death in epilepsy,
      and airway management is particularly challenging during seizure activity.
      Objective: We sought to determine if the transtracheal delivery of a bolus of
      oxygen or room air below the level of an obstruction to inflate the lungs could
      be an effective method to prolong the time available for responders seeking to
      establish a stable airway, and, if so, what could be learned about optimization
      of delivery parameters from a rat model. Methods: Rats were fitted with a t
      shaped tracheal tube for controlling access to air and for measuring airway
      pressures. After respiratory arrest from simulated laryngospasm, bolus
      transtracheal lung inflation with a volume of gas equivalent to half the vital
      capacity was delivered to the closed respiratory system as the only resuscitation
      step. Results: Bolus lung inflation was sufficient for resuscitation, improving
      cardiac function and re-establishing adequate oxygen status to support life.
      Inflation steps could be repeated and survival times were approximately 3 times
      that of non-inflated lungs. Conclusion: The properties and consequences of bolus
      lung inflation are described as a foundation for procedures or devices that can
      be useful in cases of severe laryngospasm and other cases of upper airway
      obstruction. Level of Evidence: 3.

PMID- 30186963
TI  - Temporal Bone Histopathology of X-linked Inherited Alport Syndrome.
AB  - Objective: To describe the histopathologic findings within the human cochlea in X
      linked Alport syndrome. Study Design: Histopathologic analysis of cellular
      elements within the human cochlea by light microscopy. Materials and Methods: A
      right and a left cochleae of a man with genetically confirmed X-linked Alport
      syndrome was studied post-mortem. The temporal bones underwent standard
      processing for histologic examination. The slides were examined by light
      microscopy. Graphic reconstruction of the cochlea was performed to quantify hair
      cells, pathologic changes of the stria vascularis, and loss of cochlear neuronal
      cells. Results: There was severe loss of inner hair cells and all three rows of
      outer hair cells in the apical two turns of the cochlea. The stria vascularis and
      spiral ligament showed areas of marked loss which became more prominent from base
      to apex in each ear. The spiral ganglion cell count in the Rosenthal's canal
      exhibited loss of 20% to 45% compared to matched historical controls. There was a
      zone of separation between the organ of Corti and the basilar membrane extending
      along the basal surface of Deiters cells, Hensen cells, Claudius cells and
      external sulcus cells. The tunnel of Corti and the space of Nuel were filled with
      cellular elements along the cochlea. Conclusion: The histopathologic findings of
      cochlear involvement in Alport's syndrome are basement membrane separation from
      the cells of the organ of Corti, outer and inner hair cell loss, and cellular
      infilling of the tunnel and extracellular spaces of the organ of Corti. These
      observations contribute to our understanding of the mechanism of sensorineural
      hearing loss in these patients. Level of Evidence: 

PMID- 30186964
TI  - Hypoglossal Nerve Stimulator Implantation in a Non-Academic Setting: Two-Year
      Result.
AB  - Objectives/Hypothesis: Upper Airway Stimulation (UAS) is an FDA approved
      treatment option for patients with moderate-to-severe obstructive sleep apnea
      (OSA) who could not adhere to continuous positive airway pressure (CPAP).
      Previous studies have shown UAS reduced apnea-hypopnea index (AHI) in controlled
      clinical trials and from academic institutions. We report patient outcomes and
      therapy adherence of UAS in a non-academic hospital and clinic setting. Study
      Design: Case series of consecutive patients. Methods: Consecutive implants
      completed at a community hospital between January 2015 to Feb 2017 are included
      in this report. All patients underwent baseline polysomnography (PSG) recording
      and drug-induced sleep endoscopy (DISE) prior to the implant. All patients had
      returned for standard post-implantation titration PSG at a community sleep clinic
      to validate and adjust the stimulation setting for optimal response. Results were
      in mean +/- SD, and pre- and post-implant data were compared using a paired
      student t-test. Results: A total 22 patients undergoing UAS implant were
      overweight (BMI of 28.9 +/- 5.0 kg/m2) and middle aged (63.2 +/- 11.1 years), and
      had severe OSA (AHI of 35.9 +/- 19.1). The AHI from the entire night of the
      titration study was 16.0 +/- 10.4 (P < .01, compared with baseline), and the
      treatment AHI from the sleep period when the optimal setting was programmed was
      1.2 +/- 1.1 (P < .001, compared with baseline), and 90% patients had titrated AHI
      less than 5. The lowest SpO2 increased from 81% +/- 8% at baseline to 91% +/- 3%
      at the titrated setting (P = .001). After an average follow up of 95 +/- 28.5
      days, the therapy use per night was 7.0 +/- 1.9 hours per night. The average
      postoperative ESS was 6.7 +/- 5.3 of 18 patients, a reduction from the baseline
      of 10.9 +/- 4.8. A total of 13 of 18 patients with postoperative ESS < 10, a
      measure indicated normalization of daytime sleepiness. Conclusion: Patients who
      elected to receive UAS implant surgery at a non-academic hospital and followed at
      a sleep clinic showed significant reduction in OSA severity with strong adherence
      to treatment. These results supported that UAS as a valid treatment option for
      OSA can be successfully implemented in the non-academic hospital and clinic
      settings. Level of Evidence: 4.

PMID- 30186965
TI  - Clinical efficacy of novel elastography using acoustic radiation force impulse
      (ARFI) for diagnosis of malignant thyroid nodules.
AB  - Objective: Acoustic radiation force impulse (ARFI) imaging is a recent ultrasound
      elastography technique; consequently, its efficacy is not fully known. In this
      study, we compared ARFI imaging with conventional strain elastography (SE) and
      shear wave velocities (SWVs) to evaluate the utility of ARFI imaging for
      diagnosing thyroid nodules. Subjects and Methods: In this study we examined 233
      thyroid nodules (183 benign nodules and 50 malignant nodules) isolated from human
      patients. The nodules were evaluated with SE and ARFI imaging, and SWVs of the
      nodules were simultaneously measured. ARFI images were classified using a four
      point score based on grayscale intensity of the images. The sensitivity,
      specificity, and diagnostic accuracy were compared between SE and ARFI imaging.
      Finally, SWVs for each score of SE and ARFI imaging were compared. Results: The
      new scoring system for ARFI imaging can be divided into four virtual touch
      imaging (VTI) scores. Nodules with a VTI score of 3 or 4 as determined by ARFI
      imaging were determined to be malignant. The sensitivity, specificity, and
      diagnostic accuracy, respectively, were 63.2%, 66.3%, and 65.6% for SE, compared
      with 80.0%, 86.3%, and 85.0% for ARFI imaging. The median SWVs of the nodules
      were 1.57 m/s, 1.73 m/s, 1.88 m/s, and 2.09 m/s for VTI scores of 1, 2, 3, and 4,
      respectively. The SWVs of VTI scores 3 and 4 were significantly higher than those
      of VTI scores 1 and 2. Conclusions: The diagnostic accuracy of ARFI imaging for
      differentiating malignant thyroid nodules was higher than that of SE. The VTI
      scores of the nodules accurately reflected their SWVs. Level of Evidence: 4.

PMID- 30186966
TI  - Staged Thyroidectomy: A Single Institution Perspective.
AB  - Background: The increasing use of intraoperative neuromonitoring (IONM) in
      thyroid surgery has revealed the need to develop new strategies for cases in
      which a loss of signal (LOS) occurs on the first side of a planned total
      thyroidectomy. Objectives: This study reviews the experience of the authors in
      using IONM for planned total thyroidectomy after LOS on the first thyroid lobe.
      The aims were to estimate the incidence of LOS on the first side of resection and
      to compare intraoperative strategies applied after this event. Materials and
      Methods: Intermittent IONM was performed with stimulation of both the vagal nerve
      and the recurrent laryngeal nerve (RLN) (V1, R1, R2, V2). Patients underwent pre-
      and postoperative laryngoscopy. Before surgery, patients were informed that
      staged thyroidectomy might be required. Results: This study analyzed 803
      consecutive thyroid procedures. Of these, V2 LOS (<100 mcV) occurred after first
      lobe exeresis in 23 (2.8%) procedures. The surgical procedure was stopped in 20
      cases (ie, staged thyroidectomy was performed). In three cases with malignancy
      and severe comorbidity (ASA score 3-4), total bilateral thyroidectomy was
      performed as planned. No cases of bilateral RLN palsy occurred. Postoperative
      laryngoscopy confirmed RLN palsy in 21 of the 23 cases. All true positive
      patients received speech therapy. Patients who had false positive LOS (n = 2) or
      malignancy (n = 8) and patients who were symptomatic (n = 7) received completion
      thyroidectomy within 6 months. One patient received radioactive iodine therapy
      for hyperthyroidism. Two patients received follow up. Conclusions:
      Neuromonitoring changes the surgical decision-making process in a
      multidisciplinary manner. A shared decision-making process involving the patient,
      anesthesiologist, and endocrinologist is suggested. In the case of intraoperative
      LOS on the first-operated side in a planned total thyroidectomy, the thyroid
      surgeon essentially has three options for surgery on the contralateral side: 1)
      Perform staged thyroidectomy. This option is recommended in bilateral goiter,
      Graves' disease, or low-risk thyroid carcinoma (differentiated or medullary
      thyroid carcinoma). The aim is to avoid bilateral vocal cord palsy. Two-stage
      completion surgery is delayed until recovery of ipsilateral nerve function. 2)
      Perform subtotal resection on the contralateral side ventrally to the RLN plane
      at a safe distance from the nerve. The aim is to avoid further disease recurrence
      and revision surgery. 3) Perform total thyroidectomy as planned for advanced
      thyroid carcinoma (including undifferentiated thyroid carcinoma). The aim is to
      improve disease control through radioactive iodine therapy, radiation therapy, or
      target therapy immediately after surgery. Level of Evidence: 4.

PMID- 30186967
TI  - Computerized intraligamental anesthesia in children: A review of clinical
      considerations.
AB  - Pain control by means of local anesthesia is an intrinsic part of clinical
      practice in dentistry. Several studies evaluated intraligamental anesthesia using
      a computer-controlled anesthetic device in children. There is a need to provide a
      clinical guide for the use of computerized intraligamental anesthesia in
      children. Intraligamental anesthesia using a computer-controlled anesthetic
      device was found to cause significantly lower pain perception scores and lower
      pain-related behavior than traditional techniques. This device proven to be
      effective in restorative and pulp treatment in children; however, its
      effectiveness in primary teeth extraction is controversial. It is important to
      withdraw recommendations necessity of future studies concerning the side effects
      of computerized intraligamental anesthesia in children. The present study aims to
      review different clinical aspects of computerized intraligamental anesthesia in
      children along with the side-effects, type of local anesthesia and postoperative
      pain of this technique. This study provides dentists with a clinical guide for
      the use of computerized intraligamental anesthesia.

PMID- 30186968
TI  - Efficacy of corticosteroids for postoperative endodontic pain: A systematic
      review and meta-analysis.
AB  - This systematic review aimed to analyze the efficacy of corticosteroid
      premedication compared to placebo or no treatment to reduce postoperative pain in
      endodontic patients. Randomized controlled trials (RCTs) assessing
      corticosteroids via oral, intramuscular, subperiosteal, intraligamentary or
      intracanal route compared to passive or active placebo, or no treatment were
      included. Four databases were searched: PubMed, Web of Science, Cochrane Library
      and Embase up to 2/21/2018. Risk of bias was assessed with Cochrane Risk of bias
      tool. Fourteen RCTs with 1,462 generally healthy adults in need of endodontic
      treatment were included. 50% of the studies were at unclear risk and 50% at high
      risk of bias. Meta-analysis showed Visual Analog Scale (VAS) pain at 4-6 hours
      after Inferior Alveolar Nerve Block (IANB) was significantly lower by 21 points
      (0-100 scale) in the corticosteroid group compared to the control group (95% CI 
      35 to -7; P = 0.003), however this difference was not statistically significant
      after 24 hours (P = 0.116). The route of administration was oral and
      intraligament injection. Patients who received corticosteroids prior to IANB were
      70.7% more likely to have none or mild pain 4-8 hours after treatment (P = 0.001)
      and 13.5% more likely 24 hours after IANB (P = 0.013) than patients in the
      control group. In conclusion, corticosteroid administration (oral or
      intraligamental) may clinically reduce the level of postoperative pain at 4-8
      hours after IANB, however the quality of the evidence was low/moderate due to
      risk of bias and heterogeneity. Further studies are recommended.

PMID- 30186970
TI  - Analysis of electroencephalogram-derived indexes for anesthetic depth monitoring
      in pediatric patients with intellectual disability undergoing dental surgery.
AB  - Background: Patients with intellectual disability (ID) often require general
      anesthesia during oral procedures. Anesthetic depth monitoring in these patients
      can be difficult due to their already altered mental state prior to anesthesia.
      In this study, the utility of electroencephalographic indexes to reflect
      anesthetic depth was evaluated in pediatric patients with ID. Methods: Seventeen
      patients (mean age, 9.6 +/- 2.9 years) scheduled for dental procedures were
      enrolled in this study. After anesthesia induction with propofol or sevoflurane,
      a bilateral sensor was placed on the patient's forehead and the bispectral index
      (BIS) was recorded. Anesthesia was maintained with sevoflurane, which was
      adjusted according to the clinical signs by an anesthesiologist blinded to the
      BIS value. The index performance was accessed by correlation (with the end-tidal
      sevoflurane [EtSevo] concentration) and prediction probability (with a clinical
      scale of anesthesia). The asymmetry of the electroencephalogram between the left
      and right sides was also analyzed. Results: The BIS had good correlation and
      prediction probabilities (above 0.5) in the majority of patients; however, BIS
      was not correlated with EtSevo or the clinical scale of anesthesia in patients
      with Lennox-Gastaut, West syndrome, cerebral palsy, and epilepsy. BIS showed
      better correlations than SEF95 and TP. No significant differences were observed
      between the left- and right-side indexes. Conclusion: BIS may be able to reflect
      sevoflurane anesthetic depth in patients with some types of ID; however, more
      research is required to better define the neurological conditions and/or degrees
      of disability that may allow anesthesiologists to use the BIS.

PMID- 30186969
TI  - The efficiency of topical anesthetics as antimicrobial agents: A review of use in
      dentistry.
AB  - Topical anesthetics are commonly used in oral & maxillofacial surgery to control
      pain in the oral cavity mucosa before local anesthetic injection. These
      anesthetic agents come in many forms, developed for different usages, to minimize
      adverse reactions, and for optimal anesthetic efficiency. Earlier studies have
      revealed that these agents may also limit the growth of microorganisms in the
      area of anesthetic application. Many topical anesthetic agents show different
      levels of antimicrobial activity against various bacterial strains and Candida.
      The dosage of local anesthetic agent used in some clinical preparations is too
      low to show a significant effect on microbial activity. Efficiency of
      antimicrobial activity depends on the local anesthetic agent's properties of
      diffusion within the bloodstream and binding efficiency with cytoplasmic
      membrane, which is followed by disruption of the bacterial cell membrane. The
      antimicrobial properties of these agents may extend their usage in patients to
      both control pain and infection. To develop the topical local anesthetic optimal
      usage and antimicrobial effect, a collaborating antiseptic agent may be used to
      benefit the local anesthetic. However, more research is required regarding
      minimum inhibitory concentration (MIC) and minimum bactericidal concentration
      (MBC) of topical local anesthetic agents with drug interaction between
      anesthetics and antiseptic agents.

PMID- 30186971
TI  - Analysis of the effect of oral midazolam and triazolam premedication before
      general anesthesia in patients with disabilities with difficulty in cooperation.
AB  - Background: When performing dental treatment under general anesthesia in adult
      patients who have difficulty cooperating due to intellectual disabilities,
      anesthesia induction may be difficult as well. In particular, patients who refuse
      to come into the dental office or sit in the dental chair may have to be forced
      to do so. However, for adult patients with a large physique, physical restraint
      may be difficult, while oral sedatives as premedication may be helpful. Here, a
      retrospective analysis was performed to investigate the effect of oral sedatives.
      Methods: A hospital-based medical information database was searched for patients
      who were prescribed oral midazolam or triazolam between January 2009 and December
      2017. Pre-anesthesia evaluation, anesthesia, and anesthesia recovery records of
      all patients were analyzed, and information on disability type, reason for
      prescribing oral sedatives, prescribed medication and dose, cooperation level
      during anesthesia induction, anesthesia duration, length of recovery room stay,
      and complications was retrieved. Results: A total of 97 patients were identified,
      of whom 50 and 47 received midazolam and triazolam, respectively. The major types
      of disability were intellectual disabilities, autism, Down syndrome, blindness,
      cerebral palsy, and epilepsy. Analyses of changes in cooperation levels after
      drug administration showed that anesthesia induction without physical restraint
      was possible in 56.0% of patients in the midazolam group and in 46.8% of patients
      in the triazolam group (P = 0.312). Conclusions: With administration of oral
      midazolam or triazolam, general anesthesia induction without any physical
      restraint was possible in approximately 50% of patients, with no difference
      between the drugs.

PMID- 30186973
TI  - Use of sugammadex in Rett syndrome: A case report.
AB  - Rett syndrome (RS) is a neurodevelopmental disorder characterized by loss of
      cognitive, motor, and social skills, epilepsy, autistic behavior, abnormal airway
      patterns, gastroesophageal reflux, nutritional problems, and severe scoliosis.
      Although girls with RS show normal or near-normal growth until 6-8 months, they
      lose their skills after that. The anesthetic management of these patients
      requires care because of all these clinical features. Especially in the
      postoperative period, prolonged apnea is common and extubation is delayed. In
      this case report, the effect of using sugammadex was presented in a 16-year-old
      girl with RS. The patient's all bimaxillary teeth and 4 wisdom teeth were
      extracted under general anesthesia in one session with minimal surgical trauma
      and moderate bleeding. Sugammadex can be a rapid and reliable agent for the
      reversal of the neuromuscular block in neurodegenerative patients.

PMID- 30186972
TI  - Epidural blood patch treatment of diplopia that developed after headache
      resolution in a patient with spontaneous intracranial hypotension.
AB  - Sudden headache onset may rarely be caused by spontaneous intracranial
      hypotension (SIH). Other associated symptoms in patients with SIH are nausea,
      vomiting, vertigo, hearing alteration, and visual disturbance. This case report
      describes a 43-year-old female diagnosed with SIH who developed diplopia after
      resolution of an abrupt-onset headache, which was managed with conservative
      treatments, including bed rest and hydration. She was also diagnosed with
      secondary right sixth cranial nerve palsy. Although conservative management
      relieved her headache, the diplopia was not fully relieved. Application of an
      autologous epidural blood patch successfully relieved her diplopia, even after 14
      days from the onset of visual impairment.

PMID- 30186974
TI  - Migrating foreign body in an adult bronchus: An aspirated denture.
AB  - As a safety measure, dentures are routinely removed before surgery. Aspiration of
      a denture could be catastrophic, with medicolegal implications. Foreign body
      aspiration is uncommon in adults; however, aspirations may remain asymptomatic
      and undiagnosed for long periods of time. We report an adult male who presented
      with a cough for more than 6 months. On radiography, a foreign body was found
      migrating within the tracheobronchial tree from one mainstem bronchus to the
      other, at different time points. The foreign body was later found to be a portion
      of his denture. The aspiration may have occurred at the time of a surgical
      procedure.

PMID- 30186975
TI  - Diagnosis and treatment of obstructive atelectasis after general anesthesia in a
      patient with abscess in the maxillofacial area: A case report.
AB  - The purpose of this study was to report and discuss the diagnosis and treatment
      of obstructive atelectasis secondary to pus obstruction in a patient who had
      developed a maxillofacial abscess, and to review the literature on similar cases.
      Persistently discharging pus within the oral cavity can act as an aspirate, and
      may lead to obstructive atelectasis. Additionally, maxillofacial surgery patients
      should be carefully assessed for the presence of risk factors of obstructive
      atelectasis, such as, epistaxis after nasotracheal intubation, oral bleeding, and
      mucus secretion. Furthermore, patients with these risk factors should be
      continuously followed up by monitoring SPO2, breath sounds, and chest x-ray.

PMID- 30186976
TI  - Does postural stability differ between adolescents with idiopathic scoliosis and
      typically developed? A systematic literature review and meta-analysis.
AB  - Background: Postural stability deficits have been proposed to influence the onset
      and progression of adolescent idiopathic scoliosis (AIS). This study aimed to
      systematically identify, critically evaluate and meta-analyse studies assessing
      postural stability during unperturbed stance with posturography in AIS compared
      to typically developed adolescents. Methods: Studies from four electronic
      databases (PubMed, Scopus, CINAHL, PEDro) were searched and case-control
      methodological quality assessed using a risk-of-bias assessment tool and a
      posturography methodological quality checklist. Pooled data regarding centre of
      pressure (COP) parameters such as sway area, Mediolateral (ML) and
      Anteroposterior (AP) position and range were compared for AIS and typically
      developed adolescents using Cohen's d effect size (ES) and homogeneity estimates.
      Results: Eighteen studies for quality analysis and 9 of these for meta-analysis
      were identified from 971 records. Risk-of-bias assessment identified 6 high, 10
      moderate and 2 low risk-of-bias studies. The posturography methodological quality
      checklist identified 4 low, 7 moderate and 7 high-quality studies. Meta-analysis
      was performed for sway area whereas ML and AP are presented in three different
      meta-analyses due to divergent measurement units used in the studies: ML position
      1 (MLP1), ML position 2 (MLP2) and ML range (MLR); AP position 1 (APP1), AP
      position 2 (APP2) and AP range (APR). Cohen's d showed a medium ES difference in
      sway area 0.65, 95% CI (0.49-0.63), whereas ML showed no (MLP1, MLP2) and large
      (MLR) ES differences; MLP1 0.15, 95% CI (0.08-0.22); MLP2 0.14, 95% CI (0.08
      0.19); and MLR 0.94, 95% CI (0.83-1.04). Cohen's d for AP showed small ES (APP1)
      and large ES difference (APP2 and APR); APP1 0.43, 95% CI (0.31-0.54); APP2 0.85,
      95% CI (0.72-0.97); and APR 0.98, 95% CI (0.87-1.09). Cochran's Q and Higgins I2
      showed homogeneity between studies. Conclusions: There is moderate quality
      evidence for decreased postural stability in AIS measured as COP parameters sway
      area, ML and AP range with a positional shift posteriorly in the sagittal plane.
      The findings support studying postural stability in early stage AIS and also
      prospectively identify cause and effect of the curvature as well as effectiveness
      of postural control interventions in the prevention of scoliosis progression.

PMID- 30186977
TI  - Activation of immune responses in patients with relapsed-metastatic head and neck
      cancer (CONFRONT phase I-II trial): Multimodality immunotherapy with avelumab,
      short-course radiotherapy, and cyclophosphamide.
AB  - Introduction and background: Second-line treatment of platinum-resistant
      relapsed/metastatic (R/M) head and neck cancer (HNC) is a currently unmet
      clinical need. Clinical trials showed improvement in overall survival and quality
      of life of R/M-HNC patients treated with anti-PD-1 regardless of the number of
      prior chemotherapy lines; however, the percentage of long-term survivors remains
      limited.This study aims to test the hypothesis that attacking the tumor
      microenvironment at multiple levels can increase immunogenicity of R/M-HNC
      without worsening the safety profile of immune checkpoint inhibitors.
      Methods/design: In this open label, multi-center, single-arm, Phase Ib/II, R/M
      HNC patients pretreated with at least one line of therapy containing platinum,
      fluorouracil, and cetuximab will receive a daily metronomic dose of 50 mg
      cyclophosphamide without a drug-free break, 10 mg/kg avelumab on day 1 and every
      other week until progression, and a single fraction of 8 Gy radiotherapy on day
      8. Discussion: The treatment protocol aims to reverse immune evasion of the tumor
      through a radiotherapy-induced self-vaccination effect, suppression of CD4+ CD25+
      FoxP3+ regulatory T-cell function by metronomic cyclophosphamide, and effector T
      cell reactivation owing to the inhibition of the PD-1-PD-L1 axis by avelumab.The
      immunologic interplay induced by the proposed combined treatment may
      theoretically improve the activity of avelumab without increasing its toxicity
      profile.Finally, an ancillary translational study will be extended to all the
      patients' population. Trial registration: EudraCT n. 2017-000353-39.

PMID- 30186978
TI  - An evaluation of comprehensiveness, feasibility and acceptability of a fertility
      awareness educational tool.
AB  - The World Health Organization (WHO) and World Bank have identified infertility as
      a global public health issue. Since the 1980s, WHO has advocated for a focus on
      prevention, especially where the burden of prevalence is highest, specifically in
      women from low- and middle-income countries (LMIC). The aim of the two studies
      presented here is to demonstrate a process to enhance implementation efforts in
      fertility awareness programmes that could assist in preventing some forms of
      infertility, and increase understanding of factors that could result in fertility
      problems. The fertility status awareness tool (FertiSTAT) for the Middle East was
      adapted to provide an illustrative example of requirements for region- or country
      specific adaptation. The mixed methods approach used included a survey of
      international medical experts concerning the comprehensiveness of risks included
      in the original FertiSTAT (Study I), and stakeholder meetings to assess the
      feasibility and acceptability of using an adapted FertiSTAT in the Middle East
      (Study II). The results indicate that the content of the original FertiSTAT was
      acceptable but not comprehensive in its coverage of potential risk factors; for
      example, it did not include genital tuberculosis, human immunodeficiency virus,
      consanguineous relationships and female genital mutilation/cutting. Furthermore,
      stakeholder meetings revealed that implementation in the Middle East would be
      enhanced by the use of more culturally sensitive wording. The data highlight the
      importance of implementation research with participants from LMIC, and the need
      for standardized protocols for adaptation of any fertility awareness programme or
      tool before practical application.

PMID- 30186979
TI  - Food-derived polyphenols inhibit the growth of ovarian cancer cells irrespective
      of their ability to induce antioxidant responses.
AB  - The use of plant polyphenols to prevent cancer has been studied extensively.
      However, recent findings regarding the cancer-promoting effects of some
      antioxidants have led to reservations regarding the therapeutic use of food
      derived antioxidants including polyphenols. The aim of this study was to evaluate
      the therapeutic potential of food-derived polyphenols and their use and safety in
      cancer patients. The free-radical scavenging ability of sulforaphane and various
      food-derived polyphenols including curcumin, epigallocatechin gallate,
      epicatechin, pelargonidin, and resveratrol was compared with their growth
      inhibitory effect on ovarian cancer cells. Oxidative stress and/or antioxidant
      responses and anti-proliferative pathways were evaluated after administering
      sulforaphane and polyphenols at doses at which they have been shown to inhibit
      the growth of ovarian cancer cells. No correlation was observed between their
      ability to scavenge free radicals and their ability to inhibit the growth of
      ovarian cancer cells. With the exception of epigallocatechin gallate, all of the
      antioxidants that were tested at doses that inhibited cell growth significantly
      increased NAD(P)H quinone dehydrogenase I (NQO1) expression but induced cell
      cycle arrest and/or apoptotic signaling. Epigallocatechin gallate exhibited a
      higher free radical scavenging activity but did not induce NQO1 expression at
      either the mRNA or at the protein level. Treatment with polyphenols at
      physiological doses did not significantly alter the growth of ovarian cancer
      cells or NQO1 expression. Therefore, individual food-derived polyphenols appear
      to have different anti-cancer mechanisms. Their modes of action in relation to
      their chemical properties should be established, rather than collectively
      avoiding the use of these agents as antioxidants.

PMID- 30186980
TI  - Exact and explicit traveling wave solutions to two nonlinear evolution equations
      which describe incompressible viscoelastic Kelvin-Voigt fluid.
AB  - Two nonlinear evolution equations, namely the Kadomtsev-Petviashvili (KP)
      equation which describes the dynamics of soliton and nonlinear wave in the field
      of fluid dynamics, plasma physics and the Oskolkov equation which describes the
      dynamics of an incompressible visco-elastic Kelvin-Voigt fluid are investigated.
      We deliberate exact traveling wave solutions, specially kink wave, cusp wave,
      periodic breather waves and periodic wave solutions of the models applying the
      modified simple equation method. The solutions can be expressed explicitly. The
      dynamics of obtained wave solutions are analyzed and illustrated in figures by
      selecting appropriate parameters. The modified simple equation method is reliable
      treatment for searching essential nonlinear waves that enrich variety of dynamic
      models arises in engineering fields.

PMID- 30186981
TI  - Influence of pharmacological preconditioning on the results of lifting operations
      efficiency.
AB  - : The main aim of the study is to determine the effectiveness and safety of
      lifting operations in women with varying degrees of involuntary changes of facial
      skin, in particular when applying pharmacological conditioning, with the
      objectification of the role of the latter. Materials and methods: A research and
      surgical treatment were conducted to eliminate involutional changes of various
      degrees in the facial skin of 461 women aged 35-75 years. Surface lifting was
      performed in 20.2% of patients, SMAS-lifting - 49.0%, SMAS-lifting with a three
      level endoscopic assist lift of the lower face zone was performed in 30.8% of
      women. Before the surgery in 13.2% of cases, I degree of involutional changes in
      facial skin was registered, 47.9% - grade II, 38.9% - grade III. Patients were
      divided into two comparable groups. With the standard preparation without
      additional drug correction, 299 women (64.9%) were operated on in the
      preoperative period, they made up a comparison group. The main group included 162
      (35.1%) women who underwent therapeutic conditioning before the lifting operation
      (Cytoflavin, n = 86; Actovegin n = 23; Ethylmethylhydroxypyridine succinate, n =
      32; Meldonium, n = 21; Pentoxifylline, n = 31; Vinpocetine n = 27). Instrumental
      evaluation of the skin dermal microcirculation was performed using laser Doppler
      flowmetry and estimation of transcutaneous oxygen tension. In the blood plasma,
      the parameters of free radical processes (FRP) were studied. FRP were studied in
      terms of generation of active oxygen forms by leukocytes - intensity of
      chemiluminescence basal and intensity of chemiluminescence stimulated, as well as
      antiperoxide plasma activity and malondialdehyde. Early postoperative
      complications were analyzed, the number of repeated lifting surgical corrections
      on the face was studied for 5 years. Results: The role of FRP in the pathogenesis
      of involuntary changes in the facial skin has been established. The imbalance of
      FRP was expressed in the intensification of the reactive oxygen species
      generation and products of lipid peroxidation. This correlated with disorders of
      cutaneous microcirculation and a decrease in the saturation of the facial tissues
      with oxygen, manifested by an increasing energy deficit and the severity of
      involutional skin changes. The obtained data justify the expediency of using
      pharmacological conditioning with energy correcting antioxidant medicine.
      Preoperative conditioning allowed to reduce the number of early postlifting
      complications associated with tissue trophism in a quarter, especially during
      surface lifting. In addition, in the preconditioning group, the scar was more
      cosmetic already at the seventh day after the operation. Based on the study of
      postoperative catamnesis, self-assessment data and laboratory-instrumental
      methods of skin system examination in people of different ages, it was revealed
      that while using SMAS-lifting with a three-level endoscopic-assisted lifting of
      the lower part of the face, the lowest frequency of complications and the best 5
      year effectiveness were established.

PMID- 30186984
TI  - Restoration of degraded landscapes for ecosystem services in North-Western
      Ethiopia.
AB  - Establishing exclosures has become common in Ethiopia, especially in the central
      and northern highlands, where they serve as a response to persistent forest
      degradation, affecting forest resources and ecosystem services. We investigated
      changes in vegetation composition, aboveground biomass and soil properties after
      establishing an exclosure on degraded communal grazing land in Aba-Gerima
      watershed, North-Western Ethiopia. We selected 4-yr-old exclosure and paired the
      selected exclosure with an adjacent communal grazing land. In the exclosure, we
      recorded 46 plant species representing 32 families, whereas we recorded 18 plant
      species representing 13 families in the adjacent communal grazing lands. Most of
      the identified woody species are economically important. We observed significant
      differences between the exclosure and adjacent grazing land in woody species
      richness, diversity and evenness. Exclosure displayed higher woody species
      density, basal area and aboveground woody biomass compared to the adjacent
      grazing land. Landscape position influenced vegetation composition, richness and
      diversity in the exclosure and adjacent grazing land. Significant differences
      between the exclosure and adjacent grazing land in soil properties were detected.
      The influence of landscape positions on soil properties was not consistent. At
      foot slope position, in the 0- to 15-cm and 15- to 30-cm depths, soil organic
      carbon and nitrogen content detected in exclosure were significantly higher when
      compared to the values observed in the adjacent grazing land. However,
      differences at mid and upper slope positions were not significant. The results
      support that the establishment of exclosures on degraded lands could support the
      restoration of degraded native vegetation and soil properties, which consequently
      enhance the ecosystem services that can be obtained from degraded lands.

PMID- 30186982
TI  - Role of genetic factors and ethnicity on the multiplicity of Plasmodium
      falciparum infection in children with asymptomatic malaria in Yaounde, Cameroon.
AB  - In this cross-sectional study, we investigated host genetic factors and ethnic
      variation in circulating Plasmodium falciparum merozoite surface protein 2 (msp
      2) clones among children with asymptomatic malaria. Isolates from seventy two
      asymptomatic malaria children were used for genotyping block 3 of msp-2 gene by
      nested polymerase chain reaction (PCR). Sickle cell trait and glucose-6-phosphate
      dehydrogenase (G6PD) deficiency were analysed by restriction fragment length
      polymorphism of DNA products from PCR targeting codons 6 and 68 of the beta
      globin (HBB) and G6PD genes respectively. ABO blood group was typed by
      agglutination method. A total of forty two msp-2 genotypes (20 for 3D7 and 22 for
      FC27) were detected for an average (standard error of mean) multiplicity of
      infection (MOI) of 2.45 (0.16). The MOI was statistically the same among the five
      identified ethnic groups (P = 0.83). The overall prevalence of sickle cell trait
      and G6PD deficiency were 12.50 % and 22.22 % respectively. MOI was similar
      between children with Hb AA and Hb AS genotypes (P = 0.42). MOI was significantly
      high among children with a mutant G6PD genotype (P = 0.017). MOI was
      significantly higher in blood group O than group A (P = 0.03). Our findings show
      that although ethnicity and sickle cell trait have no association with MOI, the
      association was observed with G6PD genotype and ABO group. The results suggest
      the need for extension and expansion of the current study in order to investigate
      the mechanisms involved.

PMID- 30186985
TI  - Chiral zirconium quantum dots: A new class of nanocrystals for optical detection
      of coronavirus.
AB  - A synthetic way of chiral zirconium quantum dots (Zr QDs) was presented for the
      first time using L(+)-ascorbic acid acts as a surface as well as chiral ligands.
      Different spectroscopic and microscopic analysis was performed for thorough
      characterization of Zr QDs. As-synthesized QDs exhibited fluorescence and
      circular dichroism properties, and the peaks were located at 412 nm and 352 nm,
      respectively. MTT assay was performed to test the cytotoxicity of the synthesized
      Zr QDs against rat brain glioma C6 cells. Synthesized QDs was further conjugated
      with anti-infectious bronchitis virus (IBV) antibodies of coronavirus to form an
      immunolink at the presence of the target analyte and anti-IBV antibody-conjugated
      magneto-plasmonic nanoparticles (MPNPs). The fluorescence properties of immuno
      conjugated QD-MP NPs nanohybrids through separation by an external magnetic field
      enabled biosensing of coronavirus with a limit of detection of 79.15 EID/50 MUL.

PMID- 30186983
TI  - Diversity of bacteria associated with corn roots inoculated with Canadian
      woodland soils, and description of Pseudomonas aylmerense sp. nov.
AB  - Bacteria associated with corn roots inoculated with soils collected from the
      Canadian woodlands were isolated and characterized. Genus-level identification
      based on 16S rRNA sequence analysis classified the 161 isolates in 19 genera. The
      majority (64%) of the isolates were affiliated with the genus Pseudomonas.
      Further analysis of the Pseudomonas isolates based on BLASTn and rpoD-rpoB-gyrB
      concatenated gene phylogeny revealed three unique clusters that could not be
      assigned to known species. This study reports the taxonomic description of one of
      the distinct lineages represented by two strains (S1E40T and S1E44) with P.
      lurida LMG 21995T, P. costantinii LMG 22119T, P. palleroniana LMG 23076T, P.
      simiae CCUG 50988T and P. extremorientalis LMG 19695T as the closest taxa. Both
      strains showed low ANIm (<90%) and genome-based DNA-DNA hybridization (<50%)
      values, which unequivocally delineated the new strains from the closest
      relatives. These findings were supported by multilocus sequence analysis (MLSA)
      and DNA fingerprinting. In addition, growth characteristics and biochemical tests
      revealed patterns that differed from the related species. Strains S1E40T and
      S1E44 are Gram-negative, aerobic, rod-shaped and motile by at least one
      flagellum; and grew optimally at 30  degrees C. The predominant polar lipid is
      phosphatidylethanolamine while the major respiratory quinone is ubiquinone-9.
      Based on phenotypic and genotypic data presented here, strains S1E40T and S1E44
      represent a novel species for which the name Pseudomonas aylmerense sp. nov. is
      proposed. The type strain is S1E40T (= LMG 30784T = DOAB 703T = HAMI 3696T) with
      a G + C content of 61.6%.

PMID- 30186986
TI  - Antifungal effects of ethanolic and aqueous extracts of Vitexagnus-castus against
      vaginal isolates of Candida albicans.
AB  - Background and Purpose: Vulvovaginal candidiasis is one of the most common
      infections in female genital organs, which is caused by Candida species. Candida
      albicans is the causative agent of more than 80% of infections, and the role of
      non-Candida strains in the disease etiology is less prominent. The expansion of
      Azoles resistance among C. albicans strains is considered an important medical
      problem. According to previous studies, Vitex agnus-castus (vitex) has some
      antimicrobial effects. We aimed to evaluate the anti-fungal effects of aqueous
      and alcoholic extracts of vitex against clinical vaginal isolates of C. albicans
      in comparison with fluconazole. Materials and Methods: Gas chromatography-mass
      spectrometry analysis was performed on vitex to identify its possible bioactive
      components. Forty C. albicans clinical isolates were identified by using germ
      tube, chlamydospore production, culture on CHROMagar, and polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP). Finally, after the
      extraction of vitex, drug susceptibility test was carried out according to the
      clinical laboratory standards institute (CLSI) M27-S4 document guidelines.
      Results: The major chemical components of vitex leaf as determined by gas
      chromatography included alpha-Pinene, isoterpinolene, caryophyllene, and azulene.
      The minimum inhibitory concentrations (MICs) of aqueous and alcoholic extracts of
      vitex, as well as fluconazole were within the ranges of 15.62-62.5, 7.81-15.62,
      and 0.25-8 MUg/mL, respectively. Conclusion: Our findings showed that the
      alcoholic and aqueous extracts of vitex had antifungal activity against clinical
      isolates of C. albicans. Moreover, the alcoholic extract of vitex and fluconazole
      were more effective against clinical vaginal isolates of C. albicans compared to
      the aqueous extract of vitex.

PMID- 30186987
TI  - Prevalence of vulvovaginal candidiasis in gynecological practices in Germany: A
      retrospective study of 954,186 patients.
AB  - Background and Purpose: To the best of our knowledge, no information is available
      regarding the treatment of vulvovaginal candidiasis in gynecological practices.
      The goal of this study was to analyze the prevalence of vulvovaginal candidiasis
      (VVC) and the drugs prescribed for the treatment of this condition in women
      followed in gynecological practices in Germany. Materials and Methods: All the
      women followed in 262 gynecological practices between November 2014 and October
      2016 were included in this study. The first outcome was the prevalence of
      patients diagnosed with VVC during this period. The second outcome was the
      prevalence of women with VVC who received an appropriate vaginal or systemic
      antimycotic prescription within 30 days after their first VVC diagnosis.
      Covariables included the use of gynecological/systemic antibiotics, consumption
      of oral/vaginal contraceptives, cancer, pregnancy, diabetes, and psychiatric
      diseases including depression, anxiety, and adjustment and somatoform disorders.
      Results: Between 2014 and 2016, 954,186 women were followed in gynecological
      practices, and 50,279 (5.3%) women were diagnosed with VVC during the same
      period. The use of gynecological antibiotics (OR=2.88), systemic antibiotics
      (OR=1.45), oral contraceptives (OR=1.74), and vaginal contraceptives (OR=1.84)
      were associated with an increase in the risk of VVC diagnosis. Cancer (OR=1.20)
      and pregnancy (OR=1.59) were additional risk factors. Approximately 75% of women
      diagnosed with VVC received an antimycotic prescription. The three most
      frequently prescribed drugs were clotrimazole (72%), fluconazole (14%), and
      nystatin (6%). Conclusion: More than 5% of women were diagnosed with VVC and the
      majority of them received an appropriate prescription.

PMID- 30186988
TI  - Molecular characterization of Candida dubliniensis and Candida albicans in the
      oral cavity of drug abusers using duplex polymerase chain reaction.
AB  - Background and Purpose: Candida dubliniensis is closely related to the most
      pathogenic and prevalent yeast, namely C. albicans.Candida species can
      opportunistically overgrow in vulnerable individuals and cause a variety of
      diseases. The current study aimed to identify and isolate C. dubliniensis species
      present in the Candida albicans species complex identified in the oral cavity of
      drug abusers. Materials and Methods: This study was conducted on 53 strains of C.
      albicans species complex, isolated from the oral mucosa of drug abusers in
      Isfahan, Iran. DNA extraction was accomplished through boiling procedure. Duplex
      polymerase chain reaction (PCR) was performed to amplify ITS1-5.8S-ITS2 region
      using four specific primers. Fungal species were identified based on the
      difference in the size of the bands created in the Agarose gel. Results: Out of
      the 53 isolates under study, 30 (56.6%) and 14 (26.4%) samples were identified as
      C. albicans and C. dubliniensis, respectively. In the remaining 9 samples (17%),
      both types of Candida species were confirmed. Conclusion: The findings of the
      present study revealed the presence of a noticeable amount of C. dubliniensis in
      the oral cavity of drug abusers. Therefore, the probable presence of this fungus
      should be considered during the examination of oral infection among this group.
      To date, no research has directly investigated this issue in Iran.

PMID- 30186989
TI  - Effect of combination therapy with ceftizoxime and clotrimazole in the treatment
      of otomycosis.
AB  - Background and Purpose: There are controversial findings regarding the efficacy
      of antifungal drugs in the treatment of a ruptured eardrum following fungal
      infections. Regarding this, the aim of the present study was to evaluate the
      therapeutic effect of the co-administration of antifungal and antibacterial
      agents in the treatment of otomycosis with tympanic membrane perforation.
      Materials and Methods: This analytical, clinical trial was conducted on 87
      patients with otomycosis showing no bacterial elements in the direct observation
      and culture. The study population was assigned into two groups of intervention
      (n=45) and control (n=42). The demographic and clinical data, as well as the data
      related to the direct observation and culture of the ear samples were recorded in
      a checklist. All statistical analysis was performed in SPSS (version 24).
      Results: The most prevalent symptoms in both groups were hearing loss and
      itching, and the most common finding was secretion. Aspergillus and Candida were
      the most frequent fungi isolated from the samples. After the implementation of
      combination therapy, the intervention group demonstrated a significant decrease
      in symptoms and signs, compared to the control group (P=0.005). Conclusion: The
      findings of the present study indicated that the use combination therapy with
      ceftizoxime powder and clotrimazole ointment was effective the in treatment of
      the patients with tympanic membrane rupture showing no bacterial effects in
      direct examination and culture.

PMID- 30186991
TI  - First report of Vulvovaginitis due to Cryptococcus magnus in Iran.
AB  - Background and Purpose: Cryptococcus. magnus is a non-Cryptococcus neoformans
      species isolated from certain plants, soil, air, and arctic glaciers. Case
      report: This report describes a case of a 23-year-old Iranian female with
      pruritus and vaginal irritation. Conventional tests and molecular analysis of the
      samples of vaginal discharge were performed. The mentioned analyses revealed
      Cryptococcus magnus as the causative agent of vaginal infection. The minimum
      inhibitory concentration analysis revealed that this species is susceptible to
      itraconazole, fluconazole, ketoconazole, and amphotericin B. The patient received
      200 mg of oral ketoconazole once daily for 10 days. The patient did not show any
      clinical signs of vaginal infection after six months. Conclusion: C. magnus was
      found to have the ability to cause vulvovaginitis. This is the first report of
      successful detection and treatment of vulvovaginal infection with C. magnus.

PMID- 30186990
TI  - Characterization of beta-tubulin DNA sequences within Candida parapsilosis
      complex.
AB  - Background and Purpose: Candida parapsilosis is a common cause of candidemia in
      children and patients with onco-hematological diseases, septic arthritis,
      peritonitis, vaginitis, and nail and skin infections. Regarding this, the present
      study was condcuted to evaluate intra- and inter-species variation within beta
      tubulin DNA sequence of C. parapsilosis complex in order to establish the
      utilization of this gene in the identification and phylogenetic analysis of the
      species. Materials and Methods: A total of 23 isolates representing three
      different species of C. parapsilosis complex were used in this study, all of
      which were identifed by ITS-sequencing. For the successful amplification of beta
      tubulin gene, a newly designed set of pan-Candida primers was used, followed by
      bilaterally sequence analysis for pairwise comparisons, determination of multiple
      alignments, evaluation of sequence identity levels, counting sequence difference,
      and construction of phylogenetic tree. Results: The multiple alignment of 623-629
      bp-long nucleotide (nt) sequences reflecting the beta-tubulin gene indicated an
      inter-species divergence ranging within 0-68 nt in C. parapsilosis, C.
      orthopsilosis, and C. metapsilosis with a mean similarity of 84.7% among the
      species. Meanwhile, the intra-species differences of 0-20 and 0-6 nt were found
      between the strains of C. parapsilosis and C. orthopsilosis, respectively. The
      phylogenetic tree topology was characterized by a clade made up by C.
      parapsilosis and C. orthopsilosis, while C. metapsilosis formed a related but
      separate lineage. Conclusion: Our data provided the basis for further discoveries
      of the relationship between the species belonging to C. parapsilosis complex.
      Furthermore, the findigns of the prsent study revealed the efficiency of beta
      tubulin DNA sequence data in the identification and taxonomy of C. parapsilosis
      and other pathogenic yeasts.

PMID- 30186992
TI  - Erratum for Nagesh et al., phytochemical analysis and docking study of compounds
      present in a polyherbal preparation used in the treatment of dermatophytosis.
AB  - [This corrects the article DOI: 10.29252/cmm.3.4.6.].

PMID- 30186993
TI  - Erratum for Mirhendi et al., the first case of onychomycosis in a koala
      (Phascolarctos cinereus) due to atypical isolates of Microsporum gypseum, a
      diagnostic challenge.
AB  - [This corrects the article DOI: 10.18869/acadpub.cmm.2.2.2.].

PMID- 30186994
TI  - Severe infolding of fenestrated-branched endovascular stent graft.
AB  - Infolding of a fenestrated-branched stent graft is an infrequent complication due
      to excessive oversizing. We report the case of an 89-year-old man who underwent a
      four-vessel fenestrated-branched endovascular aortic repair for a pararenal
      aortic aneurysm. Computed tomography angiography revealed severe infolding across
      the mesenteric-renal vessels. The patient was treated by angioplasty and
      placement of Palmaz stent. Cone-beam computed tomography confirmed patent
      visceral vessels with resolution of the infolding. This case illustrates an
      uncommon complication that can be prevented by modifications in the stent design
      and by immediate assessment using intraoperative cone-beam computed tomography.

PMID- 30186995
TI  - Percutaneous suction thrombectomy of large tumor thrombus causing massive
      pulmonary embolism.
AB  - We describe a patient who underwent a renal cell carcinoma resection with
      inferior vena cava thrombectomy complicated by tumor embolization. This resulted
      in massive pulmonary embolism requiring venous-arterial extracorporeal membrane
      oxygenation. The patient was ineligible for systemic or catheter-directed
      thrombolysis because of the recent surgical resection and postoperative
      hemorrhage. Hence, the patient underwent percutaneous suction thrombectomy with
      successful removal of the tumor thrombus and significant clinical improvement.
      This report represents a unique case of suction thrombectomy for the removal of
      tumor embolus from the pulmonary circulation and highlights the ability of
      suction thrombectomy in the management of massive pulmonary embolism.

PMID- 30186996
TI  - Giant cell arteritis as unusual cause of critical arm ischemia.
AB  - Giant cell arteritis is an inflammatory vasculopathy of unknown etiology that
      typically affects the carotid artery and its branches. Symptomatic involvement of
      upper extremity arteries is uncommon. We report a case of a 70-year-old woman
      with polymyalgia rheumatica who presented with critical arm ischemia,
      constitutional symptoms, and elevated erythrocyte sedimentation rate. Urgent
      revascularization by a carotid-brachial artery bypass was performed.
      Histopathologic evaluation of a specimen obtained intraoperatively from the
      occluded axillary artery confirmed the diagnosis, and corticosteroid therapy was
      initiated. Large-vessel vasculitis should be considered a rare differential
      diagnosis in occlusive disease of the upper extremity.

PMID- 30186997
TI  - Management of a rapidly expanding celiac artery aneurysm with the chimney
      technique.
AB  - Infective celiac artery aneurysm is an extremely rare diagnosis, with few
      reported cases in the literature. We present the case of a rapidly expanding
      celiac artery aneurysm involving the ostia, probably infectious, successfully
      treated in an urgent setting by aneurysm exclusion resorting to the chimney
      technique. On follow-up, computed tomography angiography revealed complete
      aneurysm thrombosis and patent celiac artery. Previous reports of endovascular
      treatment of infective celiac artery aneurysm involved its embolization. This is
      the first reported case of chimney technique used to exclude a celiac artery
      aneurysm, with a clinical suspicion of infectious etiology, preserving celiac
      artery patency. Short-term results are encouraging, but implantation of
      prosthetic material in an infected environment is a concern.

PMID- 30186998
TI  - Transapical endovascular repair of iatrogenic type A aortic dissection.
AB  - Intraoperative iatrogenic type A aortic dissection is a rare but known
      complication of cardiac surgery, with an incidence of 0.06% to 0.23%. Results are
      frequently catastrophic. The endovascular approach has made advances as an
      alternative treatment for aortic disease. However, the apical approach for
      transcatheter thoracic endovascular aortic repair is not well known. We present a
      5-year follow-up of a case of iatrogenic type A aortic dissection after minimally
      invasive mitral valve repair successfully resolved by medical stabilization and
      subsequent transapical thoracic endovascular aortic repair.

PMID- 30186999
TI  - Recanalization of previously thrombosed type II endoleak with aneurysm sac
      expansion after systemic thrombolysis.
AB  - Patients who have undergone endovascular aneurysm repair (EVAR) need lifelong
      monitoring because of the risk of aneurysm rupture secondary to delayed
      endoleaks. Thrombolytic therapy may expose patients with previous EVAR to the
      risk for development of new endoleaks. We describe a case in which a single dose
      of intravenous tissue plasminogen activator for acute ischemic stroke was
      complicated by aneurysm sac expansion secondary to a recurrent endoleak. The
      potential for a life-threatening complication may warrant routine imaging
      evaluation of the stent graft after systemic tissue plasminogen activator therapy
      for acute ischemic stroke in patients with previous EVAR.

PMID- 30187000
TI  - A transition in the leadership of Epilepsia Open(r): A journal update, thank you
      to the outgoing and introduction of the incoming Editors-in Chief.

PMID- 30187002
TI  - Systematic review of clobazam use in patients with status epilepticus.
AB  - Clobazam (CLB) is a commonly used oral antiepileptic drug (AED) that has been
      shown to be effective in various forms of epilepsy. Given its distinct 1,5
      benzodiazepine structure, rapid absorption, minimal drug interactions, and
      favorable safety profile, CLB displays unique properties when compared to other
      commonly used benzodiazepines. Recent evidence has shown that CLB may demonstrate
      therapeutic efficacy in status epilepticus (SE). The objective of this systematic
      review was to summarize the available evidence pertaining to the efficacy of CLB
      use in SE. An electronic literature search of Medline (1946 to November 6, 2017),
      Embase (1974 to November 6, 2017), and the Cochrane Library (1999 to November 6,
      2017) databases was performed to identify reports of CLB use in SE. After
      screening and full text review, a total of 15 articles were included: 8
      retrospective studies, 2 case series, and 5 case reports. Efficacy rates for CLB
      have varied among reports. Overall, based on the retrospective studies, a total
      of 76 patients with SE have been reported. CLB was introduced within 2-4 days
      from SE onset and has been reported to contribute to remission in 36 patients
      (47%). CLB maintenance dose ranged from 10 to 60 mg/day. However, the results
      need to be interpreted carefully because SE patients are a heterogeneous group
      with different etiologies and disease severities, and the response to CLB might
      vary in different patient population or seizure types. In conclusion, there is
      not sufficient evidence to determine the safety and efficacy of clobazam in the
      setting of SE. However, the current limited evidence combined with the unique
      characteristics of CLB suggest that the drug might be considered as an add-on
      option in SE patients, with a suggested dosage range of 10-60 mg/day. Prospective
      studies are needed to fully establish the role of CLB in the management of SE.

PMID- 30187001
TI  - Seizure in cerebral venous and sinus thrombosis.
AB  - Many conflicting issues exist about seizure in the setting of cerebral venous and
      sinus thrombosis (CVST). In this article we aimed to address the existing data
      regarding incidence, characteristics, predictors, treatment, and prognosis of
      acute and late seizures in patients with CVST and to prepare more practical
      information for clinicians. PubMed, Embase, Web of science and Cochrane databases
      were searched within 1966-2016 using relevant keywords. A total of 63 papers met
      the inclusion criteria. Seizures are classified as acute symptomatic seizures
      (ASS; first 14 days) and post-CVST epilepsy (PCE; after 14 days). The incidence
      had been reported in a wide range of 6.9-76% for ASS and 4-16% for PCE. Focal and
      generalized seizures were observed with different predominance. ASS commonly
      occurred in patients with loss of consciousness, focal neurological deficits,
      supratentorial lesions and thrombosis in superior sagittal sinus, straight sinus,
      and cortical veins. PCE had been predisposed by occurrence of ASS, motor deficit,
      and supratentorial lesions, particularly hemorrhage. Most experts believe that
      primary prophylaxis with antiepileptic drugs in the acute phase is not indicated.
      However, the initiation of prophylaxis after the first seizure in patients with
      supratentorial lesions or focal neurological deficit should be recommended. The
      quality of current evidence is low and most conclusions are based on expert
      opinions. More accurate reports of seizure semiology, detailed antiepileptic
      treatment plans, and outcomes are necessary to answer the existing questions.

PMID- 30187004
TI  - Discontinuation of carbamazepine due to concerns of long-term consequences of
      enzyme induction.
AB  - Objective: Treatment with carbamazepine (CBZ), a potent enzyme inducer, is known
      to affect the lipid profile, steroid, and vitamin D metabolism. Consequently, it
      has been postulated that patients on CBZ should be switched to noninducing
      antiepileptic drugs (AEDs). However, little is known about the seizure outcome
      following a CBZ switch in seizure-free patients. We aimed to address this issue
      using a controlled observational study design. Methods: Fifty-eight patients
      taking CBZ for focal epilepsy were assessed for discontinuing CBZ treatment due
      to concerns of long-term adverse-effects; 34 discontinued its therapy and 24
      continued with CBZ. Six-month seizure freedom was the primary end point.
      Furthermore, serum samples (total cholesterol (TC), low-density lipoprotein
      (LDL), high-density lipoprotein (HDL), triglycerides, sex hormone-binding
      globulin (SHBG), free testosterone, and 25-hydroxyvitamin D levels from before
      and at least 3 months after discontinuation or continuation were obtained from
      all patients. Results: Seizure-free patients had a 5-fold elevated odds of
      seizure recurrence if CBZ was discontinued (95% confidence interval [CI 0.51
      49.3; p = 0.17). A significant decrease in serum levels of TC, LDL, HDL, and SHBG
      as well as a significant increase in that of free testosterone were found in the
      discontinuation group compared with those who continued CBZ. Nonsignificant
      changes in triglycerides and vitamin D levels were detected. Significance:
      Discontinuation of CBZ in seizure-free patients seems to carry a moderate, but
      legitimate, risk of relapse. Conversely, our results indicate that CBZ might have
      unfavorable effects on serum levels of TC, LDL, HDL, SHBG, and free testosterone.

PMID- 30187003
TI  - Progress in the molecular mechanisms of genetic epilepsies using patient-induced
      pluripotent stem cells.
AB  - Research findings on the molecular mechanisms of epilepsy almost always originate
      from animal experiments, and the development of induced pluripotent stem cell
      (iPSC) technology allows the use of human cells with genetic defects for studying
      the molecular mechanisms of genetic epilepsy (GE) for the first time. With iPSC
      technology, terminally differentiated cells collected from GE patients with
      specific genetic etiologies can be differentiated into many relevant cell
      subtypes that carry all of the GE patient's genetic information. iPSCs have
      opened up a new research field involving the pathogenesis of GE. Using this
      approach, studies have found that gene mutations induce GE by altering the
      balance between neuronal excitation and inhibition, which is associated. among
      other factors, with neuronal developmental disturbances, ion channel
      abnormalities, and synaptic dysfunction. Simultaneously, astrocyte activation,
      mitochondrial dysfunction, and abnormal signaling pathway activity are also
      important factors in the molecular mechanisms of GE.

PMID- 30187006
TI  - Valproic acid utilization among girls and women in Stockholm: Impact of
      regulatory restrictions.
AB  - Objective: In November 2014, the European Medicines Agency (EMA) strengthened
      restrictions on the use of valproic acid in girls and women of childbearing
      potential. The objective of this study was to determine whether there has been a
      change in initiations of valproic acid treatment to females after the regulatory
      restrictions and to assess if such changes differed between indications (epilepsy
      and psychiatric disorder). Methods: An interrupted time-series analysis was
      conducted using all initiations of valproic acid in Stockholm, Sweden. from
      January 2011 to June 2017. Female and male patients aged 0-45 years with a
      recorded diagnosis of epilepsy and/or a psychiatric disorder were compared.
      Results: Before the EMA warning, a decline in trend of valproic acid initiations
      was seen in patients with epilepsy. After the warning, a significant decrease of
      valproic acid initiations was seen in women with a psychiatric disorder, but not
      in women with epilepsy. Significance: The regulatory warning appeared to have
      significantly influenced valproic acid initiations in women of childbearing age
      with a psychiatric disorder. No effect was seen in women with epilepsy, probably
      because the decline had started long before.

PMID- 30187005
TI  - Antiepileptic drug therapy in autoimmune epilepsy associated with antibodies
      targeting the leucine-rich glioma-inactivated protein 1.
AB  - Objective: To characterize seizure semiology and the utility of antiepileptic
      drug (AED) therapy in leucine-rich glioma inactivated-1 ( LGI1-Ab) autoimmune
      epilepsy (AE). Methods: Patients with voltage-gated potassium channel complex
      (VGKCc) titers higher than 0.02 nmol/L who were evaluated between May 2008 and
      June 2016 at the 3 Mayo Clinic sites (Arizona, Florida, or Minnesota) were
      identified. We then performed a retrospective review of those who were LGI1-Ab
      positive and were treated for seizures. Results: A total of 1,095 patients with
      VGKCc titers higher than 0.02 nmol/L were identified, in which 77 were LGI1
      positive. Of these, 56 patients with seizures were included in the analysis. Mean
      age at symptom onset was 62.9 years; 66% (n = 37) were male. The most common
      seizure semiology was focal faciobrachial dystonic seizures with preserved
      awareness (FBDS) (n = 35, 63%), followed by focal with impaired awareness (FIA)
      (n = 29, 52%), generalized tonic-clonic (GTCs) (n = 28, 50%), and focal non-motor
      seizures with preserved awareness (n = 28, 50%). The majority had more than one
      seizure type (n = 49, 88%; median = 2.5). Thirty-eight patients (68%) became
      seizure free: 29 (76%) with immunotherapy, 3 (5%) with AEDs alone, 2 (3%) with
      AEDs before any immunotherapy, and 4 (7%) with AEDs after immunotherapy.
      Levetiracetam (n = 47, 84%) and valproic acid (n = 21, 38%) were the most
      commonly used AEDs, but neither were associated with seizure freedom. Sodium
      channel blocking (NCB) AEDs were associated with seizure freedom in 4 patients
      compared to none treated with non-NCB AEDs. Regardless of class, AEDs prior to or
      apart from immunotherapy were associated with seizure freedom in only five
      patients (9%). In patients with FBDS, seizure freedom was more often associated
      with immunotherapy than AEDs (20/30 vs. 3/34, p = 0.001). Significance: Although
      FBDS are the most characteristic seizure type seen in LGI1-Ab AE, other seizure
      types including FIA and GTCs also occur. Immunotherapy was the treatment most
      frequently associated with seizure freedom in LGI1-Ab AE. In general, AEDs seemed
      to confer a very low chance for seizure freedom, although AEDs with NCB-blocking
      properties were associated with seizure freedom in a limited number.
      Levetiracetam in particular appears to be ineffective in this patient population.

PMID- 30187007
TI  - Characteristics of large patient-reported outcomes: Where can one million
      seizures get us?
AB  - Objective: To analyze data from Seizure Tracker, a large electronic seizure
      diary, including comparison of seizure characteristics among different
      etiologies, temporal patterns in seizure fluctuations, and specific triggers.
      Methods: Zero-inflated negative binomial mixed-effects models were used to
      evaluate temporal patterns of seizure events (during the day or week), as well as
      group differences in monthly seizure frequency between children and adults and
      between etiologies. The association of long seizures with seizure triggers was
      evaluated using a mixed-effects logistic model with subject as the random effect.
      Incidence rate ratios (IRRs) and odds ratios were reported for analyses involving
      zero-inflated negative binomial and logistic mixed-effects models, respectively.
      Results: A total of 1,037,909 seizures were logged by 10,186 subjects (56.7%
      children) from December 2007 to January 2016. Children had more frequent seizures
      than adults did (median monthly seizure frequency 3.5 vs. 2.7, IRR 1.26; p <
      0.001). Seizures demonstrated a circadian pattern (higher frequency between 07:00
      a.m. and 10:00 a.m. and lower overnight), and seizures were reported
      differentially across the week (seizure rates higher Monday through Friday than
      Saturday or Sunday). Longer seizures (>5 or >30 min) had a higher proportion of
      the following triggers when compared with shorter seizures: "Overtired or
      irregular sleep," "Bright or flashing lights," and "Emotional stress" (p <
      0.004). Significance: This study explored a large cohort of patients with self
      reported seizures; strengths and limitations of large seizure diary databases are
      discussed. The findings in this study are consistent with those of prior work in
      smaller validated cohorts, suggesting that patient-recorded databases are a
      valuable resource for epilepsy research, capable of both replication of results
      and generation of novel hypotheses.

PMID- 30187008
TI  - Seizures in Namibia: A study of traditional health practitioners.
AB  - Objective: Countries in sub-Saharan Africa are plagued by poor healthcare
      facilities, lack of specialist care, and limited financial resources. People with
      seizures often rely on the help of traditional health practitioners (THPs).
      Traditional health practices are not acknowledged in Namibia and remain
      unregulated and open to exploitation. We conducted a qualitative study to gain an
      understanding of THPs' perceptions and experiences in delivering seizure care in
      Namibia. Methods: This study formed part of a larger mixed-method study that
      explored seizure care among healthcare providers (HCPs) in Namibia. Semi
      structured interviews were conducted with 11 THPs in Namibia. Thematic analysis
      was used to identify themes and subthemes in the data. Themes were interpreted
      using the different levels of Bronfenbrenner's Ecological Systems Theory to
      illustrate the perceptions and experiences of THPs in the management of seizures.
      Results: THPs distinguish between seizures with physical causes and those caused
      by witchcraft, evil spirits, and supernatural forces. THPs acknowledge the role
      of Western medicine in the treatment of medically explained seizures (physical
      causes). Seizures as a result of medically unexplained symptoms (spiritual) are
      deemed best treated by traditional medicine (TM). Diagnostic and treatment
      practices are person-specific and are guided by divination and the use of plant
      and animal material. Treatment success is measured by the complete absence of
      seizures. Biomedical treatment is seen as lacking due to its focus on seizure
      control and failure to provide a permanent cure. Significance: In countries with
      limited healthcare resources, the untapped potential of THPs may play a valuable
      role in bridging the treatment gap for seizures. Incorporating THPs into the
      healthcare system depends on proper regulation and clear demarcation of roles
      between service providers. Improved referral practices and collaboration between
      service providers will be of benefit for people with seizures who are often
      exposed to stigma and discrimination.

PMID- 30187009
TI  - Child and parental sleep in young children with epilepsy: A population-based case
      control study.
AB  - Objective: To determine the prevalence of parent-reported sleep problems in young
      children with epilepsy and their parents, and to compare findings with those in a
      non-epilepsy-related neurodisability (neurodevelopmental/neurological
      difficulties) group. Method: Parents of young children (1-7 years) with epilepsy
      (n = 48 [91% ascertainment]) completed the Child Sleep Habits Questionnaire
      (CSHQ). Parents (mothers and fathers) also completed the Pittsburgh Sleep Quality
      Index (PSQI) and the Iowa Fatigue Scale (IFS) in relation to their own
      functioning. The responses of parents of children with epilepsy were compared
      with parents of developmental-, age-, and gender-matched children with
      nonepilepsy-related neurodisability (n = 48). Results: There was not a
      significant difference in the proportion of children with epilepsy and the
      children with neurodisability scoring in the at-risk range on the CSHQ (81% vs.
      71% respectively) (p = 0.232). 62% of mothers and 44% of fathers of children with
      epilepsy had 'poor quality sleep' on the PSQI; there was not a significant
      difference between mothers of children with epilepsy and those of children with
      neurodisability (p = 0.526) or IFS (p = 0.245) total scores. However, mothers of
      children with epilepsy had significantly more difficulties on the productivity
      subscale of the IFS (p = 0.004). There were no significant differences between
      fathers' scores on either measure. In the epilepsy group, child behavioral
      problems (p = 0.001) were independently associated with child sleep difficulties
      and maternal mental health problems were associated with parental sleep
      difficulties (p = 0.04) and fatigue (p = 0.018). Significance: Young children
      with epilepsy and their parents have a high rate of sleep difficulties. There is
      a need to develop effective interventions for this population, taking into
      consideration of the role of child behavioral problems and parental mental health
      difficulties.

PMID- 30187010
TI  - Post-stroke seizure-Do the locations, types and managements of stroke matter?
AB  - Objective: To determine the incidence of post-stroke seizures and the associated
      risk factors in a government-restructured hospital in Singapore. Methods: This
      retrospective study included consecutive patients (age >=21 years) admitted to
      the stroke rehabilitation facility at Changi General Hospital, Singapore, between
      June 2008 and May 2017, with a minimum post-discharge follow-up of 6 months.
      Patients with known epilepsy central nervous system infection or tumor, a history
      of neurosurgery and or missing data were excluded from study. To determine the
      incidence of seizures, the patients' hospital records, including those for all
      initial and subsequent admissions and outpatient follow-ups, were reviewed. All
      prescribed medications were checked and documented. Seizures were diagnosed on
      the basis of clinical examination with or without electroencephalography.
      Results: In total, 722 patients (women, 38%) with a mean age of 64 years were
      included. Of these, 48 (6.64%) experienced post-stroke seizures during a follow
      up period of 6-108 months. The incidence of seizures was significantly higher in
      patients with hemorrhagic stroke (42%, p = 0.010), those with ischemic partial
      anterior circulation stroke (PACS) (27%, p = 0.025), those who underwent a
      neurosurgical procedure after stroke (p < 0.001), those with a low activated
      partial thromboplastin time (APTT) at admission (mean, 25.6; p = 0.015), and
      those using levodopa (21%, p < 0.001). Neurosurgical intervention after stroke
      (odds ratio [OR] 6.2, 95% confidence interval [CI] 2.9-13.1; p < 0.001), APTT
      (per-unit increase; OR 0.86, 95% CI 0.76-0.98; p = 0.028), and underlying
      ischemic heart disease (IHD; OR 2.2, 95% CI 1.08-4.60; p = 0.029) were found to
      be independent predictors of seizure occurrence after stroke. Significance: Post
      stroke seizure incidence from our study is 6.64%, with a median follow-up of 49
      months. Among patients with stroke, those with underlying IHD, those who undergo
      a neurosurgical procedure, and those with a low APTT at admission need careful
      monitoring. Levodopa should be used with caution and withdrawn as soon as
      possible.

PMID- 30187011
TI  - Wada asymmetry in patients with drug-resistant mesial temporal lobe epilepsy:
      Implications for postoperative neuropsychological outcomes.
AB  - Objective: This study reports neuropsychological outcomes based on preoperative
      Wada testing in patients with drug-resistant mesial temporal lobe epilepsy
      (mTLE). Methods: Patient records were retrospectively reviewed as part of a
      larger database. Patients with a diagnosis of TLE based on seizure semiology and
      long-term surface video-electroencephalography (EEG) were identified. These
      patients underwent preoperative and postoperative testing including advanced
      imaging (magnetic resonance imaging [MRI]), Wada testing, and neuropsychological
      assessment. Decrements in neuropsychological function were noted in comparison of
      pre- and postoperative studies. Patients had regular follow-up in the
      multidisciplinary epilepsy clinic to assess seizure outcomes. All participants
      had Engel class I/II outcome following selective amygdalohippocampectomy (AH) via
      the inferior temporal gyrus (ITG) approach. Results: Forty-eight patients with
      electrographic and clinical semiology consistent with unilateral mTLE were
      identified. Left mTLE was identified in 28 patients (58.3%), whereas 20 patients
      (41.7%) had right mTLE. Language-dominant hemisphere resections were performed on
      23 patients (47.9%) (all left-sided surgery), whereas 25 (52.1%) had language
      nondominant resection (all right-sided and five left-sided surgery). Twenty-two
      participants (45.8%) showed no Wada memory asymmetry (No-WMA), whereas 26 (54.2%)
      exhibited Wada memory asymmetry (WMA). Postoperatively, analysis of variance
      (ANOVA) found that the No-WMA group exhibited a decline in verbal memory, but
      average scores on measures of nonverbal reasoning, general intelligence, and mood
      improved. Alternatively, patients with WMA did not show declines in memory
      postoperatively, and also exhibited improved nonverbal reasoning and general
      intelligence. Neither group exhibited reliable decline in verbal fluency or
      visual confrontation naming. Significance: Wada procedures for predicting
      surgical outcome from elective temporal surgery have been criticized and remain
      an area of active debate. However, decades of data across multiple epilepsy
      centers have demonstrated the value of Wada for reducing unanticipated
      neuropsychological adverse effects of surgical treatment. These data show that no
      Wada memory asymmetry increases the risk for neuropsychological decline following
      ITG approach for selective AH for drug-resistant mTLE.

PMID- 30187014
TI  - Elevated Troponin I Levels in Diabetic Ketoacidosis Without Obstructive Coronary
      Artery Disease.
AB  - Elevated troponin levels have been observed in a wide spectrum of patients who do
      not have ischemic heart disease, including nonacute coronary syndrome and
      cardiovascular and noncardiovascular conditions. The cases of two patients with
      diabetic ketoacidosis who had elevated troponin levels in the absence of coronary
      artery disease are presented. This clinical scenario can pose a diagnostic
      dilemma for the physician. The objective of the present report is to highlight
      the mechanism of troponin elevation in patients with diabetic ketoacidosis, in
      addition to the clinical and prognostic significance of this finding.

PMID- 30187012
TI  - Timing matters: Impact of anticonvulsant drug treatment and spikes on seizure
      risk in benign epilepsy with centrotemporal spikes.
AB  - Objective: Benign epilepsy with centrotemporal spikes (BECTS) is a common, self
      limited epilepsy syndrome affecting school-age children. Classic interictal
      epileptiform discharges (IEDs) confirm diagnosis, and BECTS is presumed to be
      pharmacoresponsive. As seizure risk decreases in time with this disease, we
      hypothesize that the impact of IEDs and anticonvulsive drug (ACD) treatment on
      the risk of subsequent seizure will differ based on disease duration. Methods: We
      calculate subsequent seizure risk following diagnosis in a large retrospective
      cohort of children with BECTS (n = 130), evaluating the impact of IEDs and ACD
      treatment in the first, second, third, and fourth years of disease. We use a
      Kaplan-Meier survival analysis and logistic regression models. Patients were
      censored if they were lost to follow-up or if they changed group status. Results:
      Two-thirds of children had a subsequent seizure within 2 years of diagnosis. The
      majority of children had a subsequent seizure within 3 years despite treatment.
      The presence of IEDs on electroencephalography (EEG) did not impact subsequent
      seizure risk early in the disease. By the fourth year of disease, all children
      without IEDs remained seizure free, whereas one-third of children with IEDs at
      this stage had a subsequent seizure. Conversely, ACD treatment corresponded with
      lower risk of seizure early in the disease but did not impact seizure risk in
      later years. Significance: In this cohort, the majority of children with BECTS
      had a subsequent seizure despite treatment. In addition, ACD treatment and IEDs
      predicted seizure risk at specific points of disease duration. Future prospective
      studies are needed to validate these exploratory findings.

PMID- 30187017
TI  - Insulin Resistance Probability Scores for Apparently Healthy Individuals.
AB  - Context: Insulin resistance (IR) can progress to type 2 diabetes. Therefore,
      timely identification of IR could facilitate disease prevention efforts. However,
      direct measurement of IR is not feasible in a clinical setting. Objective:
      Develop a clinically practical probability score to assess IR in apparently
      healthy individuals based on levels of insulin, C-peptide, and other risk
      factors. Design: Cross-sectional study. Participants: Apparently healthy
      individuals who volunteered to participate in studies of IR. Main Outcome
      Measure: IR, defined as the top tertile of steady-state plasma glucose during an
      insulin-suppression test. Results: In a study of 535 participants, insulin, C
      peptide, creatinine, body mass index (BMI), and triglycerides to high-density
      lipoprotein cholesterol ratio (TG/HDL-C) were independently associated with IR
      (all P < 0.05) in a model that included age, sex, ethnicity, BMI, blood pressure,
      insulin, C-peptide, fasting glucose, low-density lipoprotein cholesterol, TG/HDL
      C, alanine aminotransferase, and creatinine. For an IR probability score based on
      a model that included insulin, C-peptide, creatinine, TG/HDL-C, and BMI, the odds
      ratio was 26.7 (95% CI 14.0 to 50.8) for those with scores >66% compared with
      those with scores <33%. When only insulin and C-peptide were included in the
      model, the odds ratio was 15.6 (95% CI 7.5 to 32.4) for those with scores >66%
      compared with those with scores <33%. Conclusions: An IR probability score based
      on insulin, C-peptide, creatinine, TG/HDL-C, and BMI or a score based on only
      insulin and C-peptide may help assess IR in apparently healthy individuals.

PMID- 30187016
TI  - Plasma Leptin Concentration and Sympathetic Nervous Activity in Older Adults With
      Physical Dysfunction.
AB  - Context: Previous research has shown a positive relationship between plasma
      leptin and sympathetic nervous activity. High plasma leptin activate inflammatory
      cytokines and lead to muscle wasting. However, studies have detected low
      sympathetic nervous activity and high plasma leptin in older adults with muscle
      wasting, sarcopenia, and frailty. High plasma leptin do not seem to correlate
      with high sympathetic nervous activity. However, their relationship in older
      adults remains unclear. Objective: We investigated the relationship between
      plasma leptin and sympathetic nervous activity in older adults. Design Setting
      and Participants: We conducted a cross-sectional study and analyzed the results
      from 69 participants aged >=75 years. Sympathetic nervous activity was measured
      by heart rate variability, obtained from 24-hour Holter monitoring. A functional
      independence measure (FIM) and Barthel index were used to assess physical
      function. Results: The plasma leptin was higher in women (men, 3.4 +/- 2.8 ng/mL;
      women, 6.6 +/- 6.5 ng/mL; P = 0.024). Plasma leptin was negatively and
      substantially related to the FIM (beta = -0.233; P = 0.049) and Barthel index
      (beta = -0.298, P = 0.018) after adjustment for covariates. However, the data
      showed no relationship between the plasma leptin and sympathetic nervous
      activity. Conclusions: We could not detect an association between sympathetic
      nervous activity and plasma leptin in older adults. This might suggest a failure
      of the feedback system of the sympathetic nervous system, leading to muscle
      wasting in older adults.

PMID- 30187015
TI  - Mild Hypothyroidism in Childhood: Who, When, and How Should Be Treated?
AB  - Mild hypothyroidism, also known as subclinical hypothyroidism (SH), is
      biochemically defined as serum TSH levels above the upper limit of the reference
      range, in the presence of normal serum concentrations of total T4 and free T4
      (FT4). In the neonatal period, mild hypothyroidism can be defined by the presence
      of a TSH value between 6 and 20 mIU/L and normal FT4 levels. After the neonatal
      period, SH can be defined mild if TSH ranges between 4.5 and 10 mIU/L. The
      management of mild hypothyroidism in childhood is challenging. The major concern
      is to establish whether this condition should always be considered an expression
      of mild thyroid dysfunction. Indeed, the effects of untreated mild hypothyroidism
      are still not completely defined. In the neonatal period, concern exists about
      neurocognitive outcome; in children, although there is no clear evidence of
      alterations in growth or neurocognitive development, subtle cardiovascular
      abnormalities have been documented. Therefore, there is still uncertainty about
      the need of treatment across all ages, and the management should be based on the
      age of the child, the etiology, and the degree of TSH elevation, as well as on
      other patient factors. This review updates current evidences on diagnosis and
      management of mild hypothyroidism in childhood.

PMID- 30187019
TI  - Epidemiological, clinical, and immunological profile of cases at the time of HIV
      testing (a clinic-based observational cross-sectional study).
AB  - Introduction: With the availability of free antiretroviral therapy (ART),
      HIV/AIDS has become a chronic manageable disease, but its transmission still
      continues. Early testing, though desirable, is still a far-fetched goal.
      Materials and Methods: Forty-six newly detected HIV cases attending skin and
      sexually transmitted disease (STD) outpatient department (OPD) were studied.
      Careful inquiry was made to know the reason for HIV testing, marital status,
      concordance rate in married couples, and CD4 count at the time of presentation.
      Results: Of the 46 cases, 27 (59%) cases were in the age range of 20-40 years
      with 41% females and 59% males. Forty-one cases were married and cohabiting, out
      of which 19 were seroconcordant. Condom was used by 5/19 cases in seroconcordant
      group and 3/22 cases in serodiscordant group. Fourteen (30.4%) cases were tested
      for an epidemiologic reason (the most common being spouse positivity and
      antenatal care testing). Of the remaining 32 cases, the reason for testing was
      mucocutaneous manifestations in 16 cases, STD in 10 cases, and systemic illnesses
      (fever of unknown origin and weight loss) in 6 cases. Mean CD4 count was
      336/cumm, with 17 cases having CD4 count <250/cumm. Conclusion: Except one, all
      cases were tested either because they were symptomatic or were referred by health
      care provider for epidemiologic reasons. The presence of mucocutaneous
      manifestations including STD and systemic illnesses as the reason for testing as
      well as low CD4 count at the time of testing suggest less and late testing. Low
      condom use and high STD rate in married couple imply continued intramarital
      transmission. Although HIV seropositivity offers an entry point into continuum of
      comprehensive care package which includes free ART, it appears that HIV testing
      is still less and late.

PMID- 30187018
TI  - A meta-analysis on efficacy and tolerability of sildenafil for erectile
      dysfunction in patients with diabetes mellitus.
AB  - Erectile dysfunction (ED) is a common complication in patients with diabetes
      mellitus (DM). Sildenafil, a phosphodiesterase-5 inhibitor, is commonly used in
      patients with ED. This meta-analysis was planned to determine the strength of
      evidence to assess the efficacy and tolerability of sildenafil in patients with
      DM-associated ED. Electronic searches were carried out to identify randomized
      controlled trials (RCTs) which reported clinical efficacy of sildenafil in
      patients with DM-associated ED. Data were extracted and methodological quality
      was assessed. Relative Risk (RR) with 95% confidence intervals (CIs) was
      estimated for the dichotomous outcomes, and the mean difference with 95% CI was
      estimated for continuous data. Eight randomized controlled trials (RCTs)
      involving 1172 patients met with our inclusion criteria. In comparison to
      placebo, sildenafil significantly improved the overall sexual performance in
      patients of ED associated with DM with relative risk (RR) of answering "yes" to
      global efficiency question being 3.99 (95% CI: 2.58-6.18) compared to placebo.
      The rate of discontinuation due to treatment-related adverse reactions was 2.4%
      in sildenafil arm with RR of 2.67 (95% CI: 0.74-9.62). Sildenafil is an effective
      and safe medication for the treatment of ED associated with DM.

PMID- 30187020
TI  - Correlation between Venereal Diseases Research Laboratory titers and CD4 T
      lymphocyte count determined by flow cytometry in HIV-infected adults: A 5-year
      study.
AB  - Introduction: Venereal Diseases Research Laboratory (VDRL) is one of the key
      tests for the diagnosis of syphilis; however in HIV-positive individuals, it has
      been reported to give inappropriate results at times. Thus, this study was
      conducted to determine if the VDRL test titers vary with the severity of
      immunosuppression as determined by CD4 cell count. Materials and Methods: A total
      of 2630 samples from HIV-positive adults were tested by qualitative and
      quantitative VDRL test and if reactive, by Treponema pallidum hemagglutination
      (TPHA) test. CD4 cell counts were determined at the same time by flow cytometry
      (BD FACSCountTM system). Correlation between CD4 T-lymphocyte cell count and VDRL
      titers was sought for. Results: Nearly 6.7% (176/2631) of individuals were VDRL
      reactive, males more than females (7.6% vs. 5.1%, P = 0.014). Four of the VDRL
      reactive patients were found negative by TPHA test and were excluded from further
      study. VDRL titers ranged from weakly reactive to being reactive at 1:128 (median
      = 1:2). The CD4 cell count ranged from 23 cells/MUl to 883 cells/MUl (median =
      276 cells/MUl, mean = 323.9 +/- 200.9). Pearson's coefficient of correlation (R)
      between CD4 cell count and VDRL titers was calculated to be 0.0559; coefficient
      of determination (R2) was 0.0031. Conclusions: Although the correlation
      coefficient shows a positive correlation, the association was very weak.
      Therefore, CD4 cell count cannot be expected to influence VDRL titers in HIV
      positive adults significantly.

PMID- 30187021
TI  - A study of behavioral and disease patterns among transgenders in a tertiary care
      center.
AB  - Introduction: Transgenders are a group whose sexual identity, orientation, and
      practices differ from majority of the society. Aim: The aim of the study is to
      highlight the presence of infectious and noninfectious dermatological and
      venereal diseases among transgender population. Materials and Methods: A
      retrospective study was conducted on 120 transgender patients who attended DVL
      OPD from January 2011 to April 2015. The demographic profile, behavioral
      patterns, and prevalence of infectious and noninfectious dermatological and
      venereal diseases were studied. Results: All transgenders were male to females.
      Almost 46.6% (56) of transgenders belonged to age group 21-30, 25% (30) to 11-20
      and 30-40, and 3.4% to >40 years. Nearly 61.3% (74) completed high school, 14.7%
      (18) graduation, 12% (14) primary school, 9% (10) higher secondary, and 1.3% (2)
      were illiterate and postgraduates each. All had multiple sex partners at certain
      point of time, of which 25% (31) are now committed to a single partner and 15%
      (19) involved in commercial sex. The safe sexual practice was followed by 68%
      (84). Among sexual practices, oral contributed 97.3% (117), anal 92% (110.4),
      finger 9% (11), thigh 6% (7), and vaginal 24% (28.8). Of 120 patients, 63.3% (76)
      had infectious diseases, 42.5% (51) had noninfectious diseases, and 5.9% (7) had
      both. Nearly 76.3% (58) had infectious dermatological diseases 76.3 (58) and
      23.7% (18) had venereal infections. Noninfectious dermatological diseases
      accounted for 96.1% (49) and venereal diseases for 4% (2). Conclusion: There was
      relatively lower prevalence of infectious venereal diseases among transgender
      population, attributable to the good level of awareness among them.

PMID- 30187022
TI  - Cardiac complications in people living with human immunodeficiency virus/acquired
      immunodeficiency syndrome and their association with CD4+ T-cell count - A cross
      sectional study.
AB  - Introduction: Cardiac complications of HIV infection tend to occur late in the
      disease or are associated with related therapies and are therefore becoming more
      prevalent as therapy and longevity improve. Materials and Methods: The study was
      undertaken to study the common cardiovascular complications in Indian HIV
      patients and to their association with the CD4+ T-cell count. Observations and
      Conclusion: Prevalence of cardiac abnormality in our study was 24%. The
      abnormalities included LVDD (22%), pulmonary hypertension (12%), DCMP (12%),
      pericardial effusion (7%), left ventricular systolic dysfunction (5%), and right
      ventricular dysfunction (1%).

PMID- 30187023
TI  - Metabolic syndrome and cardiovascular disease risk assessment among human
      immunodeficiency virus-infected individuals on antiretroviral therapy.
AB  - Background: The association of cardiovascular risk with first-line antiretroviral
      therapy (ART) in Indians has been a matter of concern with the background of a
      high risk in South Asians. Aims: This study aimed to compare metabolic syndrome
      and its components, dyslipidemia, insulin resistance, and cardiovascular risk
      among patients on first-line ART (Group 1) with age-matched, ART-naive human
      immunodeficiency virus (HIV)-infected patients (Group 2) and normal controls
      (Group 3). Methods: Patients attending a tertiary care center in Mysore were
      enrolled in the study after obtaining informed consent and controls were chosen
      from relatives of patients. Results: The total number of patients enrolled in the
      study was 217 (males 111; females 106), and the mean age of these patients was
      34.1 +/- 7.4 years. The number of patients in Group 1 (HIV+, ART experienced) was
      76; in Group 2 (HIV+, ART naive) was 71, and in Group 3 (HIV-) was 70. There was
      no statistically significant difference in the prevalence of metabolic syndrome
      between the three groups. On comparing the components of metabolic syndrome,
      serum triglycerides (mg/dl) were significantly higher in the ART group (Group 1:
      149.5 [interquartile range (IQR): 84-187], Group 2: 108 [IQR: 74-152], and Group
      3: 141.5 [IQR: 89-192]; P = 0.014) and serum high-density lipoprotein cholesterol
      was higher in HIV-uninfected individuals (Group 1: 37.5 +/- 11.83, Group 2: 31.5
      +/- 12.23, and Group 3: 40.1 +/- 12.09; P = 0.0002). There was no association
      between metabolic syndrome, duration of HIV, and type of first-line ART. Total
      and low-density lipoprotein (LDL) cholesterol were significantly higher in the
      ART group. Homeostatic model assessment and Framingham scores did not reveal any
      significant difference across the three groups. Conclusion: HIV-infected
      individuals on ART had higher levels of triglycerides, LDL, and total
      cholesterol, but no increased cardiovascular risk compared to other groups.

PMID- 30187024
TI  - Sexual behaviors reported by a sample of human immunodeficiency virus-positive
      men who have sex with men: A descriptive study in Khon Kaen, Thailand.
AB  - Context: In Thailand, men who have sex with men (MSM) have a far higher rate of
      human immunodeficiency virus (HIV) infections. If these persons do not modify
      their behavior to safer lifestyles, they may increase the spread of HIV
      infection. Aims: This study aims to identify the behavior of HIV-positive MSM in
      comparison to their prediagnostic behaviors. Settings and Design: We conducted a
      cross-sectional study involving antiretroviral clinic (ARV) in Khon Kaen hospital
      to explore the sexual behaviors of HIV-positive MSM after the diagnosis of HIV
      infection. Subjects and Methods: HIV-positive MSM aged >=18 years were asked to
      enroll in the study. The questionnaire was administered to 114 MSM at least 3
      months after HIV diagnosis. Statistical Analysis Used: Descriptive statistics was
      used including means, frequencies, and percentage. Results: Forty percent of HIV
      positive MSM had not have sex with a man during the 12 months. Nineteen
      participants reported unprotected sex, 4.31% and 12.28% reported engaging in
      unprotected anal and oral intercourse, respectively. About 16.6% reported that
      they had practiced at-risk sexual behavior. The mean of number of partners in the
      past 3 months was 1.8. In total, 32.46% (n = 37) reported that they had
      relationships with a stable partner, while 22.80% (n = 26) indicated they
      continued relationships with casual partners. Conclusions: Our sample of HIV
      positive MSM, though aware of being infected, engage in sexual behaviors that
      could sustain transmission of HIV and other sexually transmitted infections. This
      highlights the need for a national prevention programs for persons living with
      HIV.

PMID- 30187026
TI  - A study of clinicopathological correlation of pruritic papular eruptions in HIV
      patients.
AB  - Context: Pruritic papular eruption (PPE) is a chronic eruption of papular and
      pruritic lesions of unknown etiology, symmetrically distributed over trunk and
      extremities. These are common cutaneous manifestations in HIV patients. It is an
      important cause of HIV-related morbidity. PPE can be the first marker of HIV.
      Their etiology, histopathological findings, and associated factors vary from
      region to region. There are no clear data available on the etiology, exact
      spectrum of the condition, histopathological findings, or treatment of PPE. Aims:
      The study is aimed at documenting the etiology, CD4 count, and its
      histopathological correlation in HIV-infected patients. Settings and Design: An
      observational study conducted in Government Medical College, Patiala. Subjects
      and Methods: Two-year data regarding history, HIV status, cluster of
      differentiation 4 (CD4) cell count, and skin biopsy of clinically suspected PPE
      patients with known HIV status were analyzed. Statistical Analysis Used: All the
      results were then statistically analyzed. Categorical data were analyzed by Chi
      square test, and one-way Spearman's rho test was used for multiple group
      comparison. Results: Data of 50 eligible patients were analyzed. The majority of
      the patients were female (between 21 and 50 years of age). The most common
      histopathological patterns were of papular urticaria, scabies, and drug reaction,
      and the others less common PPE were polymorphic light eruption and eosinophilic
      folliculitis. Patients with papular urticaria (32%) had significantly lower mean
      CD4 counts (157 cells/mm3), while in scabies, the mean CD4 count (376 cells/mm3)
      was higher. Conclusions: We conclude that histopathology helps in specifying the
      pattern of PPE and its etiology. It can be a marker of advanced HIV infection.
      Thus, correlation between the histopathology, clinical diagnosis, and CD4 counts
      helps to know the disease process.

PMID- 30187025
TI  - Clinico-epidemiological profile and high-risk sexual behavior among clients
      attending sexually transmitted infection clinic at a tertiary care hospital in
      North India.
AB  - Context: Sexually transmitted infections (STIs) are one of the most catastrophic
      events of health causing huge psychosocial and economic morbidity consequences.
      Aim: The study aims to study the clinico-epidemiological profile and high-risk
      sexual behavior among clients attending STI clinic at tertiary care hospital in
      North India. Materials and Methods: The present study was conducted at STI
      clinic, King George's Medical University, Lucknow, Uttar Pradesh. Data from 1283
      clients attending STI clinic between August 2015 and July 2016 were compiled
      using master client register and STI/reproductive tract infection patient-wise
      register, and a final completed data set of these patients was analyzed according
      to the aims and objectives. Results: On analyzing the various factors associated
      with high-risk sexual behavior among clients attending STI clinic marital status,
      sexual preference and employment status were found to be significantly associated
      with high-risk sexual behavior (P < 0.05). On multivariate analysis,
      unmarried/divorced/widow/separated marital status (odds ratio [OR]: 14.72; 95%
      confidence interval [CI]: 1.89-114.17; P = 0.00) and unemployed status (OR: 6.10;
      95% CI: 2.00-18.60; P = 0.02) were found to be independent predictors of high
      risk sexual behavior (unprotected sex). Conclusions: Based on findings of study,
      it is highly recommended to provide periodic screening to these STI patients for
      assessment of their sexual behavior along with specific counseling session.

PMID- 30187027
TI  - Deploying machine learning to find out the reasons for not using condom in a
      questionnaire-based study of 120 patients.
AB  - Context: Even though condom offers more than 90% protection against human
      immunodeficiency viral infections (human immunodeficiency virus) and few sexually
      transmitted infections (STIs), the overall use of condom in India is low. Many
      studies revealed that the significant barriers for not using condom were lack of
      privacy in stores, cultural differences, etc. Aims: We intended to find out the
      reasons for not using condoms in patients attending the STI clinic, by using
      questionnaire, and had applied machine learning tool to predict those reasons for
      not using condoms, from the data collected. Subjects and Methods: A questionnaire
      was administered on 120 patients of age above 10 years attending the STI clinic
      in a tertiary hospital. From the dataset obtained, we intended to understand if
      the demographic profile of the candidate could predict the reasons for the
      avoidance of condoms during sexual activity, by using machine learning algorithm
      called Support Vector Machine. Statistical Analysis Used: MS Excel worksheet to
      enter the data and Support Vector Machine algorithm were used for statistical
      analysis. Results: Respondents were 53% male, 45% female, and 2% transgender.
      Despite the knowledge of the condoms, 68% of the patients in the study did not
      use condom. The majority of the patients (41%) stated that condoms were not
      necessary when they have sexual activity with a known and consistent partner.
      With machine learning, we found that the prediction accuracy was significantly
      more than chance (73.47% +/-14%) when the feature vectors include only the
      response to Question 1. Conclusions: Results of the study identify the specific
      reasons for not using condom and help us in devising specific strategies to
      promote the condom usage. Our results from machine learning suggest that gender
      of the respondent is the best predictor in predicting the reason for the nonusage
      of condom.

PMID- 30187029
TI  - Human immunodeficiency virus neuropathy: A new mimicker of leprous neuropathy.
AB  - Peripheral neuropathy is usually the domain of the physician or neurologist.
      Still, many times patients land up in dermatology department with complaints such
      as sensory loss, paresthesia, and trophic ulcers. Usually, these patients are
      evaluated for leprosy and then referred to departments of internal medicine or
      neurology. We report one such patient who was initially seen by a dermatologist
      but was ultimately found to be suffering from human immunodeficiency virus
      neuropathy.

PMID- 30187028
TI  - AIDS-related progressive multifocal leukoencephalopathy-really rare in India: A
      case report and review of literature.
AB  - Progressive multifocal leukoencephalopathy (PML) is a rare but devastating
      disease in acquired immuno deficiency syndrome (AIDS) patients. PML in HIV/AIDS
      is rare in India and literature is limited. We are reporting a case of probable
      AIDS-related PML from Antiretroviral Therapy (ART) Centre Jabalpur. It was our
      first case of PML (possible) in 3194 registered HIV patients taking ART since
      2006.

PMID- 30187030
TI  - Homosexual and Zika virus infection: Is it a new start of new problem for gay?

PMID- 30187031
TI  - Emergence of forgotten entities.

PMID- 30187032
TI  - Ebola virus: An emerging sexually transmissible infection pathogen.

PMID- 30187033
TI  - IJSTD quiz based on articles in volume 39 issue 1.

PMID- 30187034
TI  - A novel mass spectrometry method based on competitive non-covalent interaction
      for the detection of biomarkers.
AB  - We report a novel biosensor platform based on competitive non-covalent
      interaction between ssDNA and a mass tag towards AuNPs, which detects PSA
      biomarkers sensitively, observed using MALDI MS. A detection limit of 57 pg mL-1
      has been achieved, showing an improvement of two orders of magnitude compared to
      the traditional spectroscopic method.

PMID- 30187037
TI  - Controlling reactive pathways in complex one-pot reactions using a novel shape
      selective catalyst with multifunctional active-sites.
AB  - A new kind of composite zeolite catalyst containing multi-functional reactive
      sites located in different nanopores with individual shape-selectivity was
      successfully applied to two complex one-pot (including both sequential and
      parallel) reactions. Every kind of reactant molecule was exactly catalyzed only
      for its desired reaction, thus the reactive pathways were effectively controlled.

PMID- 30187036
TI  - Antimicrobial peptide modification enhances the gene delivery and bactericidal
      efficiency of gold nanoparticles for accelerating diabetic wound healing.
AB  - Impaired angiogenesis and bacterial infection have increasingly been implicated
      as the major causes of delayed diabetic wound healing. However, there is
      currently no effective therapy. Here, we optimized a novel gene delivery system
      based on antimicrobial peptide (LL37) grafted ultra-small gold nanoparticles
      (AuNPs@LL37, ~7 nm) for the topical treatment of diabetic wounds with or without
      bacterial infection. AuNPs@LL37 combines the advantages of cationic AuNPs that
      condense DNA with those of antibacterial peptides, which are both highly
      antibacterial and essential for enhancing cellular and nucleus entry to achieve
      high gene delivery efficiency. AuNPs@LL37 combined with pro-angiogenic (VEGF)
      plasmids (AuNPs@LL37/pDNAs) significantly improved the gene transfection
      efficiency in keratinocytes compared with pristine AuNPs/pDNAs, and showed
      similar expression to Lipo2000/pDNAs (a well-known highly efficient gene
      transfection agent). Moreover, our therapeutic depot showed higher antibacterial
      ability than the free antimicrobial peptides and the cationic AuNPs alone in
      vitro and in vivo due to synergistic effects. Furthermore, the combined system
      promoted angiogenesis and inhibited bacterial infection in diabetic wounds,
      resulting in accelerated wound closure rates, faster re-epithelization, improved
      granulation tissue formation and high VEGF expression. Finally, our therapeutic
      depot was highly biocompatible in vitro and in vivo, suggesting its potential as
      a feasible way to treat chronic diabetic wounds.

PMID- 30187035
TI  - Primary tumor and pre-metastatic niches co-targeting "peptides-lego" hybrid
      hydroxyapatite nanoparticles for metastatic breast cancer treatment.
AB  - Both tumor metastasis resisting therapy (TMRT) and tumor metastasis targeting
      therapy (TMTT) attempt to improve tumor metastasis treatment, but they are
      limited by dynamic metastatic escape or insufficient micrometastases drug
      accumulation, respectively. Doxorubicin (DOX)-loaded functional peptide
      combination (PMC)-modified hydroxyapatite (HP) multi-mode nanoparticles (DPH)
      were developed to realize tumor metastasis amphibious therapy by balancing TMRT
      and TMTT. An in vivo imaging study showed that DPH had efficient drug delivery
      ability targeting to primary tumor and micrometastasis. Besides, it was found
      that cathepsin B-triggered intracellular mitochondria and nuclei dual-targeted
      treatment could enhance the antitumor effect of DOX by a synergistic effect. DPH
      treatment finally achieved both primary tumor and micrometastases reduction in
      4T1 aggressive lung metastasis models. The tumor metastasis inhibition of DPH was
      attributed to blocking the mitochondrial escape signaling pathways. The results
      also showed the enhanced anticancer benefits of DPH, which could orchestrate TMRT
      and TMTT in contrast to a mixture of DOX and PH (PMC-modified HP nanoparticles).
      Overall, we generated multi-mode nanoparticles that could flexibly realize
      amphibious therapy for metastatic cancer while reducing systemic drug exposure
      and off-target toxicities.

PMID- 30187038
TI  - Microwave-assisted ultrafast fabrication of high-performance polypyrrole
      nanoparticles for photothermal therapy of tumors in vivo.
AB  - Photothermal therapy with minimal invasiveness and high selectivity has been
      regarded as a powerful technique for tumor therapy to overcome the risks of toxic
      side effects and limited therapeutic efficacy of clinic cancer treatments. Among
      various photothermal therapeutic agents, polypyrrole (PPy) nanoparticles show a
      promising prospect in tumor ablation in vivo due to their admirable
      biocompatibility and outstanding photothermal performance. Besides, polypyrrole
      nanoparticles are extensively applied in biosensors, electrochemical sensors,
      tissue engineering, flexible microelectronics, and so on. However, the available
      synthesis methods of PPy nanoparticles are all time-consuming and seriously
      hindered their highly efficient production for diverse applications. Here we
      present a microwave-assisted strategy for the fabrication of PPy nanoparticles in
      2 min, and the required synthesis time is shortened by 120-720 times compared to
      that in traditional ways. The prepared PPy nanoparticles possess uniform size,
      favorable aqueous solubility, and enhanced photothermal performance derived from
      the stronger near-infrared absorbance. Low cytotoxicity and in vivo toxicity of
      the nanoparticles were confirmed via comprehensive assessments. The PPy
      nanoparticle-based photothermal therapy in vitro led to a remarkable death of
      tumor cells, and in vivo tumor ablation using the nanoparticles was achieved
      under mild laser irradiation with a FDA-approved safe power. The proposed
      microwave-assisted synthesis strategy opens up a facile and ultrafast way for the
      construction of organic nanoparticles and facilitates a wide range of
      applications of them in biomedicine and other fields.

PMID- 30187040
TI  - Exploring the potential of phosphotriazole 5' mRNA cap analogues as efficient
      translation initiators.
AB  - Augmenting the mRNA translation efficiency and stability by replacing the
      standard 7-methylguanosine 5'-cap with properly designed analogues is a viable
      strategy for increasing the in vivo expression of proteins from exogenously
      delivered mRNA. However, the development of novel cap analogues with superior
      biological properties is hampered by the challenges associated with the synthesis
      of such highly modified nucleotides. To provide a simpler alternative to
      traditional methods for cap analogue preparation, we have recently proposed a
      click-chemistry-based strategy for the synthesis of dinucleotide cap analogues
      and identified several triazole-containing compounds with promising biochemical
      properties. Here, we further explored the concept of CuAAC-mediated cap synthesis
      by designing and studying 'second generation' triazole-modified caps, which were
      derived from the most promising 'first generation' compounds by modifying the
      oligophosphate chain length, altering the position of the triazole moiety, or
      replacing chemically labile P-N bonds with P-O bonds. The biochemical properties
      of the new analogues were evaluated by determining their affinity for eIF4E,
      susceptibility to hDcp2-catalysed decapping, and translation efficiencies in
      vitro and in cultured cells. The results led to identification of cap analogues
      that have superior translational properties compared to standard caps and the
      parent triazole-modified compounds as well as provided directions for future
      improvements.

PMID- 30187039
TI  - A halogen bond-donor amino acid for organocatalysis in water.
AB  - Herein we report a halogen bond-donor amino acid, 4-iodotetrafluorophenylalanine,
      which behaves as a catalyst for the aqueous synthesis of bis
      (heterocyclic)methanes. We also provide experimental evidence that halogen
      bonding is a plausible explanation for the observed catalytic effect.

PMID- 30187041
TI  - Sampling the protonation states: the pH-dependent UV absorption spectrum of a
      polypeptide dyad.
AB  - When a chromophore interacts with several titratable molecular sites, the
      modeling of its photophysical properties requires to take into account all their
      possible protonation states. We have developed a multi-scale protocol, based on
      constant-pH molecular dynamics simulations coupled to QM/MM excitation energy
      calculations, aimed at sampling both the phase space and protonation state space
      of a short polypeptide featuring a tyrosine-tryptophan dyad interacting with two
      aspartic acid residues. We show that such a protocol is accurate enough to help
      in the interpretation of the experimental tyrosine UV absorption spectrum at both
      acidic and basic pH. Moreover, it is confirmed that radical tryptophan probably
      contributes to the peptide spectrum, thanks to a UV-induced electron transfer
      from tyrosine to tryptophan, ultimately shedding light on the complex pH
      dependent behavior of the peptide spectrum.

PMID- 30187043
TI  - Optically-regulated thermal energy storage in diverse organic phase-change
      materials.
AB  - Thermal energy storage and release in aliphatic phase-change materials are
      actively controlled by adding azobenzene-based photo-switches. UV activation of
      the additives induces supercooling of the composites, allowing for longer thermal
      storage at lower temperatures. The mechanism of this process is studied by
      comparing phase change behavior across diverse materials.

PMID- 30187044
TI  - Reductive activation of neptunyl and plutonyl oxo species with a
      hydroxypyridinone chelating ligand.
AB  - Oxo group activation with reduction of neptunyl(vi) and plutonyl(vi) to
      tetravalent hydroxo species by the hydroxypyridinone siderophore derivative 3,4,3
      LI-(1,2-HOPO) was investigated in the gas-phase via electrospray ionization mass
      spectrometry, in solution via Raman spectroscopy, and computationally via density
      functional theory. Dissociation of the gas-phase tetravalent complexes resulted
      in actinide-hydroxo bond cleavage.

PMID- 30187042
TI  - Peptide supramolecular materials for therapeutics.
AB  - Supramolecular assembly of peptide-based monomers into nanostructures offers many
      promising applications in advanced therapies. In this Tutorial Review, we
      introduce molecular designs to control the structure and potential biological
      function of supramolecular assemblies. An emphasis is placed on peptide-based
      supramolecular nanostructures that are intentionally designed to signal cells,
      either directly through the incorporation of amino acid sequences that activate
      receptors or indirectly by recruiting native signals such as growth factors.
      Additionally, we describe the use and future potential of hierarchical
      structures, such as single molecules that assemble into nanoscale fibers which
      then align to form macroscopic strings; the strings can then serve as scaffolds
      for cell growth, proliferation, and differentiation.

PMID- 30187045
TI  - Phenolic profile and in vitro bioactive potential of Saharan Juniperus phoenicea
      L. and Cotula cinerea (Del) growing in Algeria.
AB  - The aim of this study was to characterize the individual phenolic profile and
      antioxidant, anti-inflammatory, cytotoxic, and antimicrobial activities of
      hydroethanolic and infusion extracts prepared from Algerian Saharan Juniperus
      phoenicea L. and Cotula cinerea (Del). The phenolic profile was determined using
      a liquid chromatograph coupled to a diode array detector and an electrospray
      ionization mass spectrometer (LC-DAD-ESI/MS). A total of thirteen and nine
      individual phenolic compounds were identified in J. phoenicea and C. cinerea,
      respectively. 3-p-Coumaroylquinic acid, quercetin- and myricetin-O-pentoside were
      the major compounds present in J. phoenicea; on the other hand, C. cinerea
      presented luteolin-7-O-glucoside, luteolin-O-malonylhexoside, and 5-O
      caffeoylquinic acid as the main molecules. In general, all samples exhibited
      interesting antioxidant activity when compared to the standard Trolox, but J.
      phoenicea extracts presented the highest bioactivity. Likewise, all the samples
      exhibited anti-inflammatory activity; thus J. phoenicea hydroethanolic extracts
      showed the highest potential (88 +/- 8 MUg mL-1). In addition, their cytotoxicity
      was evaluated towards a panel of four selected cell lines (HeLa, NCI-H460, MCF-7
      and HepG2), and all the extracts showed cytotoxic effects, with J. phoenicea
      extracts being the most effective. The in vitro antimicrobial activity of the
      plant extracts was moderate, Gram-positive bacteria thus being more sensitive
      than the Gram-negative strains (MIC values between 5 and 20 mg mL-1). The present
      work suggests that J. phoenicea and C. cinerea are sources of bioactive
      ingredients with potential use in the food and pharmaceutical industries.

PMID- 30187047
TI  - Gold(i) and gold(iii) phosphine complexes: synthesis, anticancer activities
      towards 2D and 3D cancer models, and apoptosis inducing properties.
AB  - A series of gold(i), gold(iii) and cationic gold(i) complexes of tris(4
      methoxyphenyl)phosphine and tris(2,6-dimethoxyphenyl)phosphine were synthesised
      and fully characterised by spectroscopic methods. The molecular structures of
      selected complexes were also determined by X-ray diffraction analysis. The
      prepared complexes [AuX{P(C6H4-4-OMe)3}] [X = Cl (1), Br (2), I (3)],
      [AuCl3{P(C6H4-4-OMe)3}] (4), [Au{P(C6H4-4-OMe)3}2]PF6 (5), [AuX{P(C6H3-2,6
      {OMe}2)3}] [X = Cl (6), Br (7), I (8)], [AuCl3{P(C6H3-2,6-{OMe}2)3}] (9) and
      [Au{P(C6H3-2,6-{OMe}2)3}2]PF6 (10) were investigated for their anticancer
      activity against five human tumor cell lines [ovarian (SKOV-3), fibrosarcoma
      (HT1080), glioblastoma (U87MG), prostate (PC-3), and cervical (HeLa)] as well as
      against 3D spheroidal models of HeLa cells. The cationic complex 10 was found to
      exhibit a remarkably broad spectrum of anticancer activity with approximately 30
      fold higher toxicity than cisplatin against PC-3 and U87MG cancer cells; this
      complex also showed the strongest inhibition of spheroid growth in 3D models of
      HeLa cells. The mechanism of anticancer activity of these gold complexes was
      found to be strong inhibition of thioredoxin reductase, increased ROS production
      and subsequent apoptosis induction as evidenced by the sub G1 cell accumulation,
      DNA fragmentation, and caspase-3 activation.

PMID- 30187046
TI  - A tetravalent sialic acid-coated tetraphenylethene luminogen with aggregation
      induced emission characteristics: design, synthesis and application for sialidase
      activity assay, high-throughput screening of sialidase inhibitors and diagnosis
      of bacterial vaginosis.
AB  - We report a turn-on tetravalent sialic acid-coated tetraphenylethene luminogen
      (TPE4S) with excellent hydrophilicity, good stability, high sensitivity and
      unique selectivity towards sialidases, and the maximum fluorescence enhancement
      was ~40 fold. More importantly, TPE4S was successfully utilized for the screening
      of sialidase inhibitors and diagnosis of bacterial vaginosis.

PMID- 30187048
TI  - A structural model of the hierarchical assembly of an amyloid nanosheet by an
      infrared probe technique.
AB  - Rational design of amyloid-based materials requires structural insight into such
      materials. Here, we explore the use of a side-chain-based infrared (IR) probe
      technique combined with atomic force microscopy, Raman spectroscopy, UV-Vis
      spectroscopy, and thermogravimetric analysis coupled with mass spectrometry to
      elucidate the structural details of an amyloid nanosheet formed by an Abeta(16
      22) variant, KLVXFAK, where X is p-cyanophenylalanine with its side-chain cyano
      group being an IR probe. Through the structural constraints obtained with the
      combined tools, we are able to propose a novel structural model for the amyloid
      nanosheet. The nanosheet can be viewed as a stack of class 7-type steric-zipper
      like amyloid structures with a unique sheared intersheet arrangement: the beta
      sheets are stacked along a zippering axis with each individual beta-sheet sheared
      relative to its adjacent beta-sheets by two residues through the cyano-lysine
      intersheet hydrogen bond. With such a configuration, the side view of the
      nanosheet is similar to that of a stack of tilted-aligned roof tiles with each
      individual beta-sheet being each tile. In addition, this work provides a nice
      example of how to utilize the side-chain-based IR probe technique combined with
      other supplemental tools to build a hierarchical structural model for a complex
      amyloid assembly.

PMID- 30187049
TI  - Polyoxotungstates incorporated organophosphonate and nickel: synthesis,
      characterization and efficient catalysis for epoxidation of allylic alcohols.
AB  - Three new sandwich-type organophosphonate-functionalized polyoxotungstate
      clusters, [{Ni(H2O)5}x(AsW6O21)2{Ni(OOCCH2NCH2PO3)2}3] (x = 0 (Ni1), 1 (Ni2 and
      Ni3)), were successfully isolated via a "top-down" synthetic strategy. Compounds
      (Ni1-Ni3) were characterized by single crystal X-ray analysis, X-ray powder
      diffraction (XRPD), IR spectroscopy, UV-vis spectroscopy, and thermogravimetric
      analyses (TGA). Magnetic properties provide evidence for antiferromagnetic
      coupling in Ni2 and Ni3 and ferromagnetic interaction in Ni1. Catalytic studies
      of the three polyoxotungstates for the oxidation of allylic alcohols to epoxides
      have been investigated in water with H2O2 as the oxidant. All three
      polyoxotungstates exhibit efficient catalytic performance with excellent
      conversion and high selectivity at room temperature.

PMID- 30187050
TI  - Phosphine-mediated partial reduction of alkynes to form both (E)- and (Z)
      alkenes.
AB  - A mild, phosphine-mediated partial reduction of alkynyl carbonyls to the
      corresponding alkenes was developed. Tuning of the reaction conditions led to
      either the (E)- or (Z)-diastereomer with high selectivity. A range of alkynyl
      esters, amides, and ketones were reduced to form alkenes in good to high yields
      and with excellent functional group tolerance.

PMID- 30187051
TI  - Flexibility of nanolayers and stacks: implications in the nanostructuration of
      clays.
AB  - The basic structural units of adsorbing microporous materials such as clays and
      cementitious materials are flexible nanolayers. The flexibility of these layers
      is reported to play a crucial role in the structuration of these materials,
      potentially affecting therefore the thermo-mechanical behavior of such materials.
      Adsorbed fluids are structured in a discrete number of layers within the space
      between the nanolayers in these materials. This discrete nature of adsorption
      states may lead to micro-instabilities due to non-convex energy profiles. The
      transition between adsorption states may involve the bending of layers. Bending
      contributes to metastability, which is reported to be a potential source of the
      irreversibilities notably in clay behavior. In this paper, we determine the
      bending modulus of clay nanolayers by the combination of plate theory with
      molecular simulations of sodium montmorillonite. The case of clays is
      illustrative of the behavior of phyllosilicates (i.e. sheet-silicates) which are
      ubiquitous minerals in the Earth's crust. We discuss the conditions in which clay
      particles, i.e. a stack of nanolayers, can be viewed as thin plates. Estimations
      of the bending modulus according to the hydration state and dimensions of clay
      particles are provided. We analyze the implications of the flexibility of the
      layers in the behavior of a stack of layers as well as in the transitions between
      adsorption states. The energy barrier associated with bending of clay layers and
      the characteristic length of bending in such transitions are provided. Our
      results contribute to a better understanding of the nanostructure of layered
      adsorbing materials.

PMID- 30187053
TI  - Shear rate dependent margination of sphere-like, oblate-like and prolate-like
      micro-particles within blood flow.
AB  - This study investigates the shear rate dependent margination of micro-particles
      (MPs) with different shapes in blood flow through numerical simulations. We
      develop a multiscale computational model to handle the fluid-structure
      interactions involved in the blood flow simulations. The lattice Boltzmann method
      (LBM) is used to solve the plasma dynamics and a coarse-grained model is employed
      to capture the dynamics of red blood cells (RBCs) and MPs. These two solvers are
      coupled together by the immersed boundary method (IBM). The shear rate dependent
      margination of sphere MPs is firstly investigated. We find that margination of
      sphere MPs dramatically increases with the increment of wall shear rate [small
      gamma, Greek, dot above]omega under 800 s-1, induced by the breaking of rouleaux
      in blood flow. However, the margination probability only slowly grows when [small
      gamma, Greek, dot above]omega > 800 s-1. Furthermore, the shape effect of MPs is
      examined by comparing the margination behaviors of sphere-like, oblate-like and
      prolate-like MPs under different wall shear rates. We find that the margination
      of MPs is governed by the interplay of two factors: hydrodynamic collisions with
      RBCs including the collision frequency and collision displacement of MPs, and
      near wall dynamics. MPs that demonstrate poor performance in one process such as
      collision frequency may stand out in the other process like near wall dynamics.
      Specifically, the ellipsoidal MPs (oblate and prolate) with small aspect ratio
      (AR) outperform those with large AR regardless of the wall shear rate, due to
      their better performance in both the collision with RBCs and near wall dynamics.
      Additionally, we find there exists a transition shear rate region 700 s-1 <
      [small gamma, Greek, dot above]omega < 900 s-1 for all of these MPs: the
      margination probability dramatically increases with the shear rate below this
      region and slowly grows above this region, similar to sphere MPs. We further use
      the surface area to volume ratio (SVR) to distinguish different shaped MPs and
      illustrate their shear rate dependent margination in a contour in the shear rate
      SVR plane. It is of significance that we can approximately predict the
      margination of MPs with a specific SVR. All these simulation results can be
      potentially applied to guide the design of micro-drug carriers for biomedical
      applications.

PMID- 30187054
TI  - A photo-degradable injectable self-healing hydrogel based on star poly(ethylene
      glycol)-b-polypeptide as a potential pharmaceuticals delivery carrier.
AB  - As one of the most promising biomaterials, injectable self-healing hydrogels have
      found broad applications in a number of fields such as local drug delivery.
      However, controlled release of drugs in hydrogels is still difficult to realize
      up to now. Here, we report a novel photo-degradable injectable self-healing
      hydrogel based on the hydrophobic interaction of a biocompatible four-arms star
      polymer, poly(ethylene glycol)-b-poly(gamma-o-nitrobenzyl-l-glutamate). The
      hydrophobic interaction between poly(gamma-o-nitrobenzyl-l-glutamate) not only
      connects poly(ethylene glycol)-b-poly(gamma-o-nitrobenzyl-l-glutamate) together
      with a crosslink but also provides a hydrophobic domain to encapsulate
      hydrophobic pharmaceuticals such as doxorubicin (DOX). Due to the dynamic
      character of the hydrophobic interaction, the hydrogel exhibits excellent
      injectable and self-healing ability. In particular, the photolabile o-nitribenzyl
      ester group is cleaved under UV irradiation. As a result, the hydrophobic domain
      transforms into the hydrophilic one and the embedded DOX is released effectively.
      An increasing release ratio of DOX dramatically enhances the apoptosis ratio of
      HeLa cells. We expect these attractive properties may be beneficial to practical
      applications of the hydrogel as an effective local drug delivery means in a truly
      physiological environment.

PMID- 30187055
TI  - Probing the organization and dynamics of two DNA chains trapped in a nanofluidic
      cavity.
AB  - Here we present a pneumatically-actuated nanofluidic platform that has the
      capability of dynamically controlling the confinement environment of
      macromolecules in solution. Using a principle familiar from classic devices based
      on soft-lithography, the system uses pneumatic pressure to deflect a thin nitride
      lid into a nanoslit, confining molecules in an array of cavities embedded in the
      slit. We use this system to quantify the interactions of multiple confined DNA
      chains, a key problem in polymer physics with important implications for
      nanofluidic device performance and DNA partitioning/organization in bacteria and
      the eukaryotes. In particular, we focus on the problem of two-chain confinement,
      using differential staining of the chains to independently assess the chain
      conformation, determine the degree of partitioning/mixing in the cavities and
      assess coupled diffusion of the chain center-of-mass positions. We find that
      confinement of more than one chain in the cavity can have a drastic impact on the
      polymer dynamics and conformation.

PMID- 30187056
TI  - Regio-specific prenylation of pterocarpans by a membrane-bound prenyltransferase
      from Psoralea corylifolia.
AB  - Prenylated pterocarpans are valuable natural products that play significant roles
      in plant defence and possess diverse biological activities. However, structural
      diversity of prenylated pterocarpans is still limited. Prenyltransferases (PTs)
      could catalyze the transfer of prenyl moieties to acceptor molecules and increase
      the structural diversity and biological activity of natural products. Up to date,
      only two pterocarpan PTs have been identified from plants. In this study, a new
      pterocarpan prenyltransferase gene, designated as PcM4DT, was identified from
      Psoralea corylifolia. The deduced polypeptide is predicted to be a membrane-bound
      protein with eight transmembrane regions. Functional characterization of
      recombinant PcM4DT demonstrated this enzyme could catalyze C-4 prenylation of
      pterocarpans, and exhibited strict substrate specificity to maackiain and 3
      hydroxy-9-methoxy-pterocarpan. It also showed a strict donor specificity to
      DMAPP. Furthermore, removal of the putative transit peptide of PcM4DT obviously
      increased the catalytic activity (up to 90%). PcM4DT represents the first PT
      identified from the Psoralea genus.

PMID- 30187057
TI  - Palladium-catalyzed cascade carboesterification of norbornene with alkynes.
AB  - An efficient and convenient palladium-catalyzed cascade carboesterification of
      norbornenes (NBE) with alkynes has been accomplished to afford functionalized
      alpha-methylene gamma-lactone and tetrahydrofuran derivatives in good to
      excellent yields. This new strategy exhibits excellent atom- and step-economy,
      good functional group tolerance and broad substrate scope. In particular, NBE
      palladium species was proposed to be the key intermediate in the catalytic cycle
      to suppress the beta-H elimination process. Notably, the developed protocol
      provides a straightforward and practical tool for the construction of diverse
      oxygen-containing heterocycle frameworks, illustrating a promising application in
      synthetic and pharmaceutical chemistry.

PMID- 30187058
TI  - Multi-scale progressive failure mechanism and mechanical properties of
      nanofibrous polyurea aerogels.
AB  - The nonlinear mechanical properties, deformation and failure mechanisms of
      polyurea aerogels (PUAs) were investigated using a multi-scale approach that
      combines nanoindentation, analytical and computational modeling. The atomistic
      structure of primary particles of PUAs and their mechanical interactions were
      investigated with molecular dynamics simulations. From nanoindentation we
      identified four deformation and failure modes: free ligament buckling, cell
      ligament bending, stable cell collapsing, and ligament crush induced strain
      hardening. The corresponding structural evolution during indentation and strain
      hardening were analyzed and modeled. The material scaling properties were found
      to be dependent on both the relative density and the secondary particle size of
      PUAs. Using a porosity-dependent material constitutive model, a linear
      relationship was found between the strain hardening index and secondary particle
      size instead the conventional power-law relationship. Finally, the structural
      efficiency of PUAs with respect to the capability for energy absorption is
      evaluated as a function of structural parameters and base polymeric material
      properties.

PMID- 30187059
TI  - Silver(i)/base-promoted propargyl alcohol-controlled regio- or stereoselective
      synthesis of furan-3-carboxamides and (Z)-enaminones.
AB  - A novel and facile regioselective synthesis of furan-3-carboxamides by a
      silver(i)/base-promoted reaction of propargyl alcohol with 3-oxo amides has been
      demonstrated. This one-pot protocol provides a rapid synthetic approach to
      diverse trisubstituted furan-3-carboxamides via cascade nucleophilic addition,
      intramolecular cyclization, elimination, and isomerization reactions. Employing a
      substituted propargyl alcohol, (Z)-enaminones have been obtained with high
      stereoselectivities by a Ag2CO3-promoted reaction starting from 3-oxo amides via
      C-N bond cleavage.

PMID- 30187060
TI  - Two time scales for self and collective diffusion near the critical point in a
      simple patchy model for proteins with floating bonds.
AB  - Using dynamic Monte Carlo and Brownian dynamics, we investigate a floating bond
      model in which particles can bind through mobile bonds. The maximum number of
      bonds (here fixed to 4) can be tuned by appropriately choosing the repulsive,
      nonadditive interactions among bonds and particles. We compute the static and
      dynamic structure factor (intermediate scattering function) in the vicinity of
      the gas-liquid critical point. The static structure exhibits a weak tetrahedral
      network character. The intermediate scattering function shows a temporal decay
      deviating from a single exponential, which can be described by a double
      exponential decay where the two time scales differ approximately by one order of
      magnitude. This time scale separation is robust over a range of wave numbers. The
      analysis of clusters in real space indicates the formation of noncompact clusters
      and shows a considerable stretch in the instantaneous size distribution when
      approaching the critical point. The average time evolution of the largest
      subcluster of given initial clusters with 10 or more particles also shows a
      double exponential decay. The observation of two time scales in the intermediate
      scattering function at low packing fractions is consistent with similar findings
      in globular protein solutions with trivalent metal ions that act as bonds between
      proteins.

PMID- 30187061
TI  - Ultrafast spectroscopic studies of composition-dependent near-infrared-emitting
      alloyed CdSeTe quantum dots.
AB  - In this study, optical and structural characterizations of near-infrared-emitting
      alloyed CdSeTe quantum dots (QDs) are measured after the dissolution in toluene.
      Luminescence spectra are obtained from alloyed CdSeTe QDs under 800 nm
      femtosecond laser excitation. With increasing pump fluence, the line width or
      full width at half maximum (FWHM) of photoluminescence (PL) spectrum becomes
      larger than 10 nm due to increasing temperature. Ultrafast spectroscopic
      properties of CdSeTe QDs are investigated by means of time-resolved PL, transient
      absorption (TA) and Z scan techniques. Moreover, open-aperture (OA) Z scan
      measurement is used to clarify the composition and pump fluence dependence of
      optical nonlinearity under femtosecond laser excitation. With increasing pump
      fluence, evolution from saturable absorption to reverse saturable absorption in
      CdSeTe QDs is observed. The transition process is analyzed via a phenomenological
      model based on nonlinear absorption coefficient and saturation intensity, which
      indicates that CdSeTe QDs have potential for applications in all-optical
      switching devices.

PMID- 30187062
TI  - A diffusion-driven fabrication technique for anisotropic tubular hydrogels.
AB  - A bio-inspired, simple, and versatile diffusion-driven method to fabricate
      complex tubular hydrogels is reported. The controlled diffusion of small ions
      from a pre-designed core hydrogel through a biopolymer reservoir solution causes
      the self-gelation of biopolymers with an anisotropic ordered structure on the
      surface of the core hydrogel. By controlling the concentration, diffusion time,
      and flow direction of the ions, as well as the size and shape of the core,
      various types of complex tubular-shaped hydrogels with well-defined 3D
      architectures were fabricated. The mechanical properties of the designed alginate
      based tubular hydrogels were highly tunable and comparable to those of native
      blood vessels. The method was applied to form a living-cell encapsulated tubular
      hydrogel, which further strengthens its potential for biomedical applications.
      The method is suitable for biopolymer-based reaction-diffusion systems and
      available for further research on the fabrication of functional biomaterials with
      various biopolymers.

PMID- 30187063
TI  - In-depth understanding of interfacial crystallization via Flash DSC and enhanced
      energy storage density in ferroelectric P(VDF-CTFE)/Au NRs nanocomposites for
      capacitor application.
AB  - High-capacity or high-power-density capacitors are being actively investigated
      for portable electronics, electric vehicles, and electric power systems. We
      describe the filler system in dielectric nanocomposites with a small loading of
      Au nanorods [NRs] to elucidate the mechanism of interfacial crystallization
      behavior including the crystallization kinetics, and crystalline morphology and
      structure, and to investigate the intrinsic causes for concurrent great
      improvements in the dielectric constant and energy density in the nanocomposite
      system. Remarkly, at high crystallization temperature, the addition of Au NRs,
      which are used as heterogeneous nucleators, can reduce the nucleation barrier,
      resulting in accelerating the crystallization rate. However, the crystallization
      rate slows down at low temperatures because the addition of Au NRs limited the
      mobility of poly(vinylidene fluoride-chlorotrifluoroethylene) [P(VDF-CTFE)]
      chains, and thus enhanced the diffusion barrier. Furthermore, the addition of NRs
      has a huge impact on the crystalline morphology and structure which changes from
      large paraelectric alpha-phase spherulites with TGTG' conformations into minor
      ferroelectric gamma-phase spherulites with T3GT3G' conformations, and also
      produces more exogenous interfaces between the lamellar crystals and amorphous
      regions, resulting in a higher dielectric constant and higher electric energy
      density in P(VDF-CTFE)/Au NRs nanocomposites. Our approach provides a facile and
      straightforward way to design or understand PVDF-based polymers for their
      practical applications in high-energy-density capacitors.

PMID- 30187064
TI  - Studies on sugar puckering and glycosidic stabilities of 3'-amino-5'
      carboxymethyl-3',5'-dideoxy nucleoside mimics.
AB  - The synthesis of nucleoside amino acid monomers and dimers has been carried out
      to evaluate and characterize the impact of the neutral amide backbone on key
      attributes like puckering of the sugar rings and glycosidic bond strengths of
      these analogs. The conformational analysis suggests that amide-linked nucleotides
      have a high predilection towards N-type conformers. The glycosidic bond strength
      was found to be slightly weaker compared to ribonucleosides under acidic
      conditions at high temperatures. The results will be helpful to explore in future
      the development of fully amide-linked oligonucleotides for therapeutic purposes.

PMID- 30187065
TI  - Direct immunoassays and their performance - theoretical modelling of the effects
      of antibody orientation and associated kinetics.
AB  - The orientation and activity of antibodies immobilized on solid surfaces are of
      direct relevance to many immunosensing applications. We therefore investigate a
      mathematical model which estimates the fraction of antibodies which are available
      for reaction in a randomly adsorbed sample. Numerical simulations are presented
      which highlight the separate effects of antibody orientation, accessibility and
      loss of binding ability on the amount of captured antigen. The assay response can
      then be expressed as a function of total antibody density and used for optimizing
      the surface coverage strategy under various conditions.

PMID- 30187066
TI  - Splitting and separation of colloidal streams in sinusoidal microchannels.
AB  - The control of the distribution of colloidal particles in microfluidic flows
      plays an important role in biomedical and industrial applications. A particular
      challenge is to induce cross-streamline migration in laminar flows, enabling the
      separation of colloidal particles according to their size, shape or elasticity.
      Here we show that viscoelastic fluids can mediate cross-streamline migration of
      deformable spherical and cylindrical colloidal particles in sinusoidal
      microchannels at low Reynolds numbers. For colloidal streams focused into the
      center of the channel entrance this leads to a symmetric stream-splitting and
      separation into four substreams. The degree of stream splitting and separation
      can be controlled via the flow rates, viscoelasticity of the focusing fluid, and
      the spatial microchannel modulation with an upper limit when reaching the
      microchannel walls. We demonstrate that this effect can be used to separate
      flexible particles of different size and shape. This methodology of cross-stream
      migration has thus great potential for the passive separation of colloids and
      cells in microfluidic channels.

PMID- 30187067
TI  - Self-assembly of DNA-tetraphenylethylene amphiphiles into DNA-grafted nanosheets
      as a support for the immobilization of gold nanoparticles: a recyclable catalyst
      with enhanced activity.
AB  - Preventing the aggregation of NPs and their recovery are the two major hurdles in
      NP based catalysis. Immobilization of NPs on a support has proven to be a
      promising strategy to overcome these difficulties. Herein we report the design of
      high aspect ratio two-dimensional (2D) crystalline DNA nanosheets formed from the
      amphiphilicity-driven self-assembly of DNA-tetraphenylethylene amphiphiles and
      also demonstrate the potential of DNA nanosheets for the immobilization of
      catalytically active NPs. The most remarkable feature of this approach is the
      high loading of NPs in a non-aggregated manner, and hence exhibiting enhanced
      catalytic activity. Recycling of NP loaded nanosheets for several cycles without
      reduction in catalytic efficiency by simple ultrafiltration is also demonstrated.

PMID- 30187068
TI  - Hole gas accumulation in Si/Ge core-shell and Si/Ge/Si core-double shell
      nanowires.
AB  - Core-shell nanowires (NWs) composed of silicon and germanium can be used to
      realize high electron (hole) mobility transistors (HEMTs) by suppressing impurity
      scattering due to their band offset structure and selective doping. Boron doped p
      type Si/intrinsic-Ge (i-Ge) core-shell NW structures are selected to study this
      phenomenon. To produce HEMT devices, hole gas accumulation must be controlled in
      the impurity undoped i-Ge shell layers. Spectral change in the Ge optical phonon
      is detected with increased B doping in p-Si core NWs, showing hole gas
      accumulation in this system. We also fabricate p-Si/i-Ge/p-Si core-double shell
      NWs to more clearly demonstrate hole gas accumulation in the i-Ge layers.

PMID- 30187069
TI  - Structure, orientation, and dynamics of water-soluble ions adsorbed to basal
      surfaces of calcium monosulfoaluminate hydrates.
AB  - Transport of water molecules and chloride ions in nanopores of hydrated cement
      paste (HCP) is proven to adversely affect the long-term durability of reinforced
      concrete structures exposed to seawater or deicing salts. The resistance against
      chloride attack is primarily associated with the chloride binding capacity of the
      main HCP constituents. Experimental tests revealed that AFm phases of HCP play a
      central role in binding the chloride ions. However, many aspects of AFm-solution
      interactions were largely unknown, especially at their interfaces. This was the
      motivation of the current study, in which the atomistic processes underlying the
      transport of water-soluble ions are investigated in detail using the classical
      molecular dynamics (MD) method. To this end, an aqueous layer containing various
      concentrations of sodium chloride solution is sandwiched between two basal
      surfaces of calcium monosulfoaluminate hydrate, which is the most abundant phase
      of AFm. The adsorption mechanisms of water molecules and diffusing ions are then
      characterized for inner- and outer-sphere distance ranges from the basal surfaces
      of monosulfoaluminate. It is found that the self-diffusion coefficient of the
      chloride and sodium ions present in the outer-sphere range are 83% and 47% larger
      than those residing in the inner-sphere range. With increasing the distance from
      the solid surface, an increase in the self-diffusion coefficient is captured.
      This increase in mobility is larger for chloride ions than sodium ions. This can
      be understood based on the observation that the inner- and outer-sphere complex
      formation are the governing adsorption mechanisms for the chloride and sodium
      ions, respectively.

PMID- 30187070
TI  - Development of G-quadruplex ligands for selective induction of a parallel-type
      topology.
AB  - G-Quadruplex structures (G4s) in guanine-rich regions of DNA play critical roles
      in various biological phenomena, including replication, translation, and gene
      expression. The G4-forming DNAs can form three kinds of topologies, i.e.,
      parallel, anti-parallel, and hybrid. In this paper, we present G4 ligands L2H2
      2M2EA-6OTD (3) and L2G2-2M2EG-6OTD (4) bearing tetra-aminoalkyl and 
      guanidinylalkyl side chains, respectively, in a macrocyclic hexaoxazole
      structure. These ligands efficiently induce the parallel-type topology of
      telomeric G4 regardless of the effects of cations. Titration with 4 results in a
      drastic topology switch to the parallel topology from the anti-parallel structure
      induced by the structurally related ligand L2H2-6OTD (1).

PMID- 30187071
TI  - Directly drawing high-performance capacitive sensors on copying tissues.
AB  - We report here a facile, green and cost-effective fabrication of high-performance
      capacitive pressure sensors by drawing loop-and disc-shaped graphite electrode
      arrays on copying tissues. Graphene oxide enhanced foam-like paper is prepared as
      an efficient dielectric layer. The paper-based capacitive pressure sensor enables
      sensitive detection of finger touch, motion and proximity.

PMID- 30187072
TI  - Molecular signature of polyoxometalates in electron transport of silicon-based
      molecular junctions.
AB  - Polyoxometalates (POMs) are unconventional electro-active molecules with a great
      potential for applications in molecular memories, providing efficient processing
      steps onto electrodes are available. The synthesis of the organic-inorganic
      polyoxometalate hybrids [PM11O39{Sn(C6H4)C[triple bond, length as m
      dash]C(C6H4)N2}]3- (M = Mo, W) endowed with a remote diazonium function is
      reported together with their covalent immobilization onto hydrogenated n-Si(100)
      substrates. Electron transport measurements through the resulting densely-packed
      monolayers contacted with a mercury drop as a top electrode confirms their
      homogeneity. Adjustment of the current-voltage curves with the Simmon's equation
      gives a mean tunnel energy barrier PhiPOM of 1.8 eV and 1.6 eV, for the Silicon
      Molecules-Metal (SMM) junctions based on the polyoxotungstates (M = W) and
      polyoxomolybdates (M = Mo), respectively. This follows the trend observed in the
      electrochemical properties of POMs in solution, the polyoxomolybdates being
      easier to reduce than the polyoxotungstates, in agreement with lowest unoccupied
      molecular orbitals (LUMOs) of lower energy. The molecular signature of the POMs
      is thus clearly identifiable in the solid-state electrical properties and the
      unmatched diversity of POM molecular and electronic structures should offer a
      great modularity.

PMID- 30187073
TI  - Independent control over residual silver content of nanoporous gold by
      galvanodynamically controlled dealloying.
AB  - A new procedure was developed and characterized for the galvanodynamically
      controlled dealloying (GCD) of AuxAg100-x alloys to obtain nanoporous gold (npAu)
      mainly as an unsupported catalyst material for partial oxidation of alcohols.
      Such catalysts require residual Ag content of less than 1 at%. GCD was compared
      to the preparation of npAu by potentiostatically controlled deallyoing (PCD) and
      free corrosion (FC). The main advantage of GCD is the ability to obtain npAu with
      a predetermined residual Ag content including residual Ag contents below 1 at%
      while retarding the coarsening of the ligaments. For PCD and FC, there is a
      strong increase of ligament size with decreasing residual Ag content because the
      longer times required for dealloying unavoidably lead to coarsening of the npAu
      structure. On the other hand, GCD also prevented too high initial current density
      that leads to cracking of the samples and prevents formation of mechanically
      stable monoliths. GCD tolerates different compositions of the starting alloy for
      AuxAg100-x within the tested composition range (20 at% <= xAu <= 30 at%). The
      samples obtained by GCD were tested for methanol and ethanol oxidation and showed
      favorable characteristics for partial oxidation of methanol to methyl formate and
      of ethanol to ethyl acetate.

PMID- 30187074
TI  - Effects of the terminal donor unit in dyes with D-D-pi-A architecture on the
      regeneration mechanism in DSSCs: a computational study.
AB  - This theoretical study on dye-sensitized solar cells (DSSCs) includes design
      strategies for dye donor units to improve the efficiency of DSSCs, and further
      illuminates the organic dye regeneration mechanism. We have designed a series of
      new organic sensitizers based on a D-D-pi-A architecture to exhibit easy electron
      transfer and to have remarkable light harvesting properties in the visible region
      by density functional theory (DFT) and time-dependent (TD)-DFT calculations.
      Furthermore, the interaction of the organic sensitizers with the conventional
      redox electrolyte using the triiodide/iodide couple (I3-/I-) is investigated. Our
      calculations indicate that incorporation of strong electron-donating groups
      remarkably improves the charge transfer characteristics, optoelectronic
      properties and rapid dye regeneration as compared to less electron donating
      substituents. In addition, our study demonstrates the possibility of second
      electron injection from the oxidized dye complex to the semiconductor surface,
      which further confirms our recently proposed dye regeneration mechanism.

PMID- 30187075
TI  - Supercapacitor with high cycling stability through electrochemical deposition of
      metal-organic frameworks/polypyrrole positive electrode.
AB  - Electrochemical deposition is an environment-friendly method for functional film
      fabrication, benefiting from the facile tuning of structure and properties of the
      film. Metal-organic frameworks (MOFs) play a significant role in the field of
      energy sources because of their porous nature, large specific surface area and
      metal ion binding sites. However, the application of such materials is limited by
      their inherent insulator-like characteristics and poor electrical conductivity.
      In this study, we designed and fabricated a composite material comprising metal
      organic framework/polypyrrole as the positive electrode of a supercapacitor via
      smear and electrodeposition methods. Electrochemical properties of the electrode
      materials were studied through galvanostatic charge/discharge (GCD) and cyclic
      voltammetry (CV) tests. The positive electrode has an excellent specific
      capacitance of 284.3 F g-1 (180.7 mF cm-2) with 1 mA cm-2 current density.
      Furthermore, this material as a positive electrode shows high cycling stability
      after 40 000 cycles (100.7% capacitance retention). This strategy can be extended
      to fabricate other MOFs and MOFs/conducting polymers composite electrodes for
      supercapacitors.

PMID- 30187076
TI  - Cycloheptyl-fused N,N,N'-chromium catalysts with selectivity for vinyl-terminated
      polyethylene waxes: thermal optimization and polymer functionalization.
AB  - Five chromium(iii) chloride complexes, [2-{(Ar)N[double bond, length as m
      dash]CMe}-9-{N(Ar)}C10H10N]CrCl3 (Ar = 2,6-Me2C6H3Cr1, 2,6-Et2C6H3Cr2, 2,6-i
      Pr2C6H3Cr3, 2,4,6-Me3C6H2Cr4, 2,6-Et2-4-MeC6H2Cr5), each chelated by a sterically
      and electronically different cycloheptyl-fused N,N,N'-bis(imino)pyridine, have
      been synthesized by the reactions of CrCl3(THF)3 with the corresponding ligand
      (L1/L1'-L5/L5'). The molecular structure of Cr2 highlights both the steric
      properties exerted by the inequivalent N-2,6-ethylphenyl groups and the puckering
      of the fused cycloheptyl ring; a distorted octahedral geometry is conferred about
      the metal center. On activation with methylaluminoxane (MAO) or modified MAO
      (MMAO), Cr1-Cr5 displayed their optimal activity for ethylene polymerization at
      temperatures between 70 and 80  degrees C with the least sterically demanding Cr1
      proving the most productive (1.44 * 107 g (PE) per mol (Cr) per h). The
      polyethylenes formed are of low molecular weight (Mw range: 0.66-3.56 kg mol-1)
      with narrow molecular weight distributions and display high levels of end-group
      unsaturation. Furthermore, the amenability of these vinyl-terminated
      polyethylenes to undergo functionalization via epoxidation has been demonstrated.

PMID- 30187077
TI  - The Influence of 6-Prenylnaringenin and Selected Non-prenylated Flavonoids on the
      Activity of Kv1.3 Channels in Human Jurkat T Cells.
AB  - The influence of a prenylated flavonoid-6-prenylnaringenin (6-PR) and selected
      non-prenylated flavonoids: acacetin, chrysin, baicalein, wogonin, and luteolin on
      the activity of voltage-gated potassium channels Kv1.3 was investigated in human
      leukemic Jurkat T cells. Electrophysiological measurements were accompanied by
      studies on the cytotoxic effect of the examined compounds on Jurkat T cells.
      Electrophysiological studies were performed using the whole-cell patch-clamp
      technique. Cell viability was determined using the MTT assay. 6-PR inhibited
      Kv1.3 channels in Jurkat T cells in a concentration-dependent manner. The
      estimated value of the half-blocking concentration (EC50) was about 5.76 uM.
      Among non-prenylated flavonoids, acacetin and chrysin inhibited Kv1.3 channels in
      Jurkat T cells when applied at the concentration of 30 uM, whereas baicalein,
      wogonin, and luteolin were ineffective at this concentration. The inhibitory
      effects of acacetin and chrysin on Kv1.3 channels were significantly less potent
      than the inhibition caused by 6-PR. All tested compounds inhibited growth of
      Jurkat T cells in a concentration-dependent manner. Wogonin and chrysin were the
      most cytotoxic flavonoids tested, whereas baicalein and 6-PR were the least
      cytotoxic compounds. In accordance to our hypothesis the prenylated flavonoid (6
      PR) was much more effective inhibitor of Kv1.3 channels than non-prenylated
      compounds selected for this study. The inhibition of Kv1.3 channels by 6-PR,
      acacetin, and chrysin was not related to cytotoxicity of these compounds. The
      channels' inhibition might be involved in anti-proliferative and pro-apoptotic
      effects of 6-PR, acacetin and chrysin observed in cancer cell lines expressing
      these channels.

PMID- 30187078
TI  - [Diagnostic imaging of drug-induced osteonecrosis of the jaw].
AB  - Drug-induced osteonecrosis of the jaw represents a relatively new, multifactor
      induced disease. Diseases with increased bone resorption are widely treated with
      antiresorptive drugs. Due to the active bone metabolism, especially in the lower
      jaw, it can lead to osteonecrosis if the barrier function in the oral cavity is
      impaired and it may be complicated by systemic comorbidities depending on
      duration, intensity, and application of antiresorptive therapy. Due to the
      special influence of these changes on the quality of life and because of the
      complex therapy management, the early detection and determination of the extent
      of the lesion(s) by imaging is of particular importance. The orthopantomography
      (panoramic radiography) of the jaw provides a good basic examination, especially
      for the detection of dental causes as a possible differential diagnosis. Three
      dimensional imaging techniques such as computed tomography and in particular
      magnetic resonance imaging can detect bone changes much more sensitively and
      detect the manifestation of complex pathologies in higher stages of disease.

PMID- 30187079
TI  - Welcome to the third training pillar of IJPH: Young Researcher Editorials.

PMID- 30187080
TI  - [Depressive and somatoform disorders in persons with a Turkish migration
      background in Germany].
AB  - BACKGROUND: Migration is a risk factor for the onset of mental disorders.
      Epidemiologic studies indicate that there is an increased prevalence of
      depressive and somatoform disorders in individuals with a Turkish migration
      background in Germany. OBJECTIVES: The aim of this review article is to determine
      the impact of sociocultural factors on depressive and somatoform disorders in
      individuals with a Turkish migration background in Germany. MATERIALS AND
      METHODS: The systematic review is based on 23 studies identified in PubMed and
      PsycINFO. RESULTS: Acculturation, perceived discrimination and the socioeconomic
      status affect the severity of mental disorders, and impair the access to the
      health care system as well as to psychotherapy. Women with a Turkish migration
      background represent a particularly vulnerable group in this context. CONCLUSION:
      Multiple factors influence the increased prevalence of depressive and somatoform
      disorders in individuals with a Turkish migration background in Germany. Most of
      the identified studies suffer from significant methodological restrictions and as
      such do not allow generalization to the whole population of individuals with a
      Turkish migration background in Germany. There is a lack of national surveys and
      a need for longitudinal studies in representative population samples.

PMID- 30187081
TI  - Kinematic posture analysis of orthodontists in their daily working practice.
AB  - PURPOSE: The aim of this study is to conduct a kinematic analysis of occupational
      posture in orthodontists. METHODS: A representative sample of 21 (13 female/8
      male) residents in orthodontics and orthodontists was studied. The CUELA system
      collects kinematic data of the occupational posture. Alongside the kinematic
      analysis, the tasks performed on-site were also subject to a detailed
      computerized analysis. Data analysis comprised the evaluation and comparison of
      joint angle distribution in accordance with ergonomic standards categorized as
      neutral, moderate or awkward posture. RESULTS: The most common activities were
      executed in a seated position. During "treatment" (28% of total time)
      participants most often worked with a straight back (84.7%), whereas a "bent or
      twisted" torso posture was observed 23.4% of the time. For head and cervical
      spine, the 75th and 95th percentiles presented worse (higher) values during
      treatment as compared to non-orthodontic activities. The seated position next to
      the patient during treatment showed a stronger inclination of the thoracic spine
      to the right and an inclination of the lumber spine to the left. CONCLUSIONS:
      Orthodontists do take characteristic postures during treatment activities with
      highest angle values. The postures differ in the area of head and cervical spine
      with regard to the various activities carried out in the 3 categories.

PMID- 30187082
TI  - Influence of physician evaluation portals on orthodontist selection by patients.
AB  - OBJECTIVE: This survey aimed to determine the influence of physician evaluation
      portals (PEP) on a patient's choice of physicians, particularly orthodontists.
      MATERIALS AND METHODS: Questionnaires were used to collect sociodemographic data,
      reasons for orthodontist selection, type of Internet use, as well as information
      on the knowledge, use and evaluation of 14 popular PEPs. A total of 506
      questionnaires were evaluated, and a descriptive statistical evaluation was
      conducted using the chi2 test. RESULTS: The majority of the respondents selected
      orthodontists on the basis of personal recommendations by other physicians (35%),
      family/friends (33%) or patient referral (14%). Currently, the most popular
      portals in Germany, which are mostly found through Internet searches, are
      jameda.de (36%) and arztauskunft.de (19%). A total of 5% of the respondents have
      already used a PEP to evaluate a physician. Moreover, 70% of the respondents
      described PEPs as helpful, 28% as recommendable and 2% use PEPs regularly.
      Knowledge of PEPs is correlated with the level of educational attainment (p =
      0.024) and the frequency of Internet use (p < 0.001). CONCLUSION: On the
      selection of healthcare providers, particularly orthodontists, PEPs have little
      influence. Patients select physicians on the basis of personal recommendations.
      Physicians' concerns about negative evaluations on PEPs are unfounded given the
      low level of awareness of PEPs by the general populace.

PMID- 30187083
TI  - The Histological Composition of Capsular Contracture Focussed on the Inner Layer
      of the Capsule: An Intra-Donor Baker-I Versus Baker-IV Comparison.
AB  - BACKGROUND: Capsular contracture remains one of the major complications after
      breast implantation surgery. The extent of capsular contraction is scored using
      the Baker scale. The aim of this study was to compare intra-individual Baker-I
      with Baker-IV capsules, and in particular the prevalence and histological
      properties of the inner capsule layer. METHODS: Twenty capsules from ten patients
      were included after bilateral explantation surgery due to unilateral capsular
      contracture (Baker-IV) after cosmetic augmentation with textured implants. All
      capsules underwent (immune-)histochemical analysis: haematoxylin-eosin
      (morphology), CD68 (macrophages), cytokeratin (epithelial cells) and vimentin
      (fibroblasts), and were visually scored for cell density and the presence of an
      inner layer and measured for thickness. RESULTS: Baker-IV (n = 10) capsules were
      significantly thicker compared to Baker-I (n = 10) capsules (P = 0.004). An inner
      layer was present in 8 Baker-I capsules. All Baker-I capsules were vimentin and
      CD68-positive and cytokeratin-negative. Positive vimentin was seen throughout the
      inner layer, and CD-68 staining was observed adjacent to the intermediate capsule
      layer. In contrast, only 2 Baker-IV capsules had an inner layer, of which only 1
      showed the same profile as Baker-I capsules (P = 0.016). No cytokeratin
      positivity was seen in any capsule. In Baker-IV capsules, outer layers showed
      more positivity for both vimentin and CD68. CONCLUSION: The inner layer is
      morphologically consistent with synovial metaplasia and is more prevalent in
      healthy, uncontracted Baker-I capsules. This inverse relation between the
      presence of the inner layer and higher Baker classification or pathological
      contracture could indicate a protective role of the inner layer against capsular
      contracture formation. 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- 30187084
TI  - Low rates of recanalization for wide-necked aneurysms treated with stenting after
      balloon-assisted coiling: combination of techniques delivers stable and improved
      results during follow-up.
AB  - PURPOSE: In the treatment of wide-necked aneurysms, stenting may be required
      after balloon-assisted coiling (BAC) for reconstructing the lumen/flow of the
      parent artery in cases of coil herniation. The potential benefits and
      complications of both techniques remain unclear when used together. Our aim was
      to assess the safety and long-term angiographic outcomes of stenting after BAC.
      METHODS: Retrospective review of 87 unruptured wide necked aneurysms (in 80
      patients) treated with BAC and requiring stent placement at the final stage of
      the procedure due to coil prolapse. Aneurysm characteristics, technical issues,
      clinical records, and MR results were assessed. Post-treatment and follow-up
      angiograms were evaluated by two independent reviewers and categorized as
      "stable," "further thrombosis," or "recanalization." RESULTS: The mean maximum
      diameter was 9.1 +/- 4.7 mm and aspect ratio 1.20 +/- 0.47. Complete and near
      complete initial occlusion were observed in 53 (60.9%) and 28 (32.2%) of all
      treated aneurysms, respectively. Angiographic follow-up (80 aneurysms; mean,
      34.68 +/- 25.26 months) revealed stability and further thrombosis in 92.4%
      (74/80). Recanalization was observed in six cases (7.5%, 6/83), four of which
      were retreated. No significantly different outcomes were found in terms of
      aneurysm size (p = 0.641). Transient and reversible procedure-related
      complications occurred in eight (9.2%), minor permanent deficits in 2.3%, and
      major deficits, including death, in four cases (4.6%). CONCLUSION: Our results
      suggest that treatment of wide-necked aneuryms with stent placement after BAC
      yields low recanalization rates and enhanced angiographic outcomes in long-term
      follow-up.

PMID- 30187086
TI  - Principles of adoptive T cell therapy in cancer.
AB  - Adoptive cell therapy (ACT) utilizing either tumor-infiltrating lymphocyte (TIL)
      derived T cells or T cells genetically engineered to express tumor recognizing
      receptors has emerged as a powerful and potentially curative therapy for several
      cancers. Many ACT-based therapies have recently entered late-phase clinical
      testing, with several T cell therapies already achieving regulatory approval for
      the treatment of patients with B cell malignancies. In this review, we briefly
      outline the principles of adoptively transferred T cells for the treatment of
      cancer.

PMID- 30187087
TI  - Polymorphism of duck MHC class molecules.
AB  - Major histocompatibility complex class I (MHC I) molecules are critically
      involved in defense against pathogens, and their high polymorphism is
      advantageous to a range of immune responses, especially in duck displaying biased
      expression of one MHC I gene. Here, we examined MHC I polymorphism in two duck
      (Anas platyrhynchos) breeds from China: Shaoxing (SX) and Jinding (JD). Twenty
      seven unique UAA alleles identified from the MHC I genes of these breeds were
      analyzed concerning amino acid composition, homology, and phylogenetic
      relationships. Based on amino acid sequence homology, allelic groups of Anas
      platyrhynchos MHC I (Anpl-MHC I) were established and their distribution was
      analyzed. Then, highly variable sites (HVSs) in peptide-binding domains (PBD)
      were estimated and located in the three-dimensional structure of Anpl-MHC I. The
      UAA alleles identified showed high polymorphism, based on full-length sequence
      homology. By adding the alleles found here to known Anpl-MHC I genes from
      domestic ducks, they could be divided into 17 groups and four novel groups were
      revealed for SX and JD ducks. The UAA alleles of the two breeds were not
      divergent from the MHC I of other duck breeds, and HVSs were mostly located in
      the peptide-binding groove (PBG), suggesting that they might determine peptide
      binding characteristics and subsequently influence peptide presentation and
      recognition. The results from the present study enrich Anpl-MHC I polymorphism
      data and clarify the distribution of alleles with different peptide-binding
      specificities, which might also accelerate effective vaccine development and help
      control various infections in ducks.

PMID- 30187085
TI  - Efferocytosis in the tumor microenvironment.
AB  - Within the course of a single minute, millions of cells in the human body will
      undergo programmed cell death in response to physiological or pathological cues.
      The diminished energetic capacity of an apoptotic cell renders the cell incapable
      of sustaining plasma membrane integrity. Under these circumstances, intracellular
      contents that might leak into the surrounding tissue microenvironment, a process
      referred to as secondary necrosis, could induce inflammation and tissue damage.
      Remarkably, in most cases of physiologically rendered apoptotic cell death,
      inflammation is avoided because a mechanism to swiftly remove apoptotic cells
      from the tissue prior to their secondary necrosis becomes activated. This
      mechanism, referred to as efferocytosis, uses phagocytes to precisely identify
      and engulf neighboring apoptotic cells. In doing so, efferocytosis mantains
      tissue homeostasis that would otherwise be disrupted by normal cellular turnover
      and exacerbated further when the burden of apoptotic cells becomes elevated due
      to disease or insult. Efferocytosis also supports the resolution of inflammation,
      restoring tissue homesostasis. The importance of efferocytosis in health and
      disease underlies the increasing research efforts to understand the mechanisms by
      which efferocytosis occurs, and how a failure in the efferocytic machinery
      contributes to diseases, or conversely, how cancers effectively use the existing
      efferocytic machinery to generate a tumor-tolerant, immunosuppressive tumor
      microenvironment. We discuss herein the molecular mechanisms of efferocytosis,
      how the process of efferocytosis might support a tumor 'wound healing' phenotype,
      and efforts to target efferocytosis as an adjunct to existing tumor treatments.

PMID- 30187088
TI  - A New Species of the gamma-Proteobacterium Francisella, F. adeliensis Sp. Nov.,
      Endocytobiont in an Antarctic Marine Ciliate and Potential Evolutionary
      Forerunner of Pathogenic Species.
AB  - The study of the draft genome of an Antarctic marine ciliate, Euplotes petzi,
      revealed foreign sequences of bacterial origin belonging to the gamma
      proteobacterium Francisella that includes pathogenic and environmental species.
      TEM and FISH analyses confirmed the presence of a Francisella endocytobiont in E.
      petzi. This endocytobiont was isolated and found to be a new species, named F.
      adeliensis sp. nov.. F. adeliensis grows well at wide ranges of temperature,
      salinity, and carbon dioxide concentrations implying that it may colonize new
      organisms living in deeply diversified habitats. The F. adeliensis genome
      includes the igl and pdp gene sets (pdpC and pdpE excepted) of the Francisella
      pathogenicity island needed for intracellular growth. Consistently with an F.
      adeliensis ancient symbiotic lifestyle, it also contains a single insertion
      sequence element. Instead, it lacks genes for the biosynthesis of essential amino
      acids such as cysteine, lysine, methionine, and tyrosine. In a genome-based
      phylogenetic tree, F. adeliensis forms a new early branching clade, basal to the
      evolution of pathogenic species. The correlations of this clade with the other
      clades raise doubts about a genuine free-living nature of the environmental
      Francisella species isolated from natural and man-made environments, and suggest
      to look at F. adeliensis as a pioneer in the Francisella colonization of
      eukaryotic organisms.

PMID- 30187089
TI  - Abiotic and Biotic Factors Affecting the Ingestion Rates of Mixotrophic
      Nanoflagellates (Haptophyta).
AB  - Mixotrophic haptophytes comprise one of several important groups of mixotrophic
      nanoflagellates in the pelagic environment. This study aimed to investigate if
      phagotrophy in mixotrophic haptophytes is regulated by light or other factors in
      the surface (SE) and bottom (BE) of the euphotic zone in the subtropical
      northwestern Pacific Ocean. We estimated the rates of bacterial ingestion by
      haptophytes using fluorescently labeled bacteria (FLBs) and fluorescence in situ
      hybridization. Haptophyte diversity and abundance were also investigated in the
      same sampling area. The annual mean abundance of haptophytes was 419 +/- 85.6
      cells mL-1 in both SE and BE. Cells 3-5 MUm in size were the dominant group in
      all haptophytes and accounted for majority of bacteria standing stock removed by
      haptophytes (53%). Most haptophyte ingestion rates (IRs) were not significantly
      different between the two layers (average SE ingestion rate: 12.5 +/- 2.29 bac
      Hap-1 h-1; BE: 14.7 +/- 3.03 bac Hap-1 h-1). Furthermore, the haptophyte IRs were
      negatively correlated with nitrate concentrations in the SE and positively
      correlated with bacterial abundances in the BE, which accounts for the
      significantly high IRs in August 2012 and 2013. These findings imply that
      mixotrophic haptophytes in this region had different factors affecting
      phagotrophy to adapt to the ambient light intensity alterations between SE and
      BE.

PMID- 30187090
TI  - What Exactly is Meant by "Loss of Domain" for Ventral Hernia? Systematic Review
      of Definitions.
AB  - Large ventral hernias are a significant surgical challenge. "Loss of domain"
      (LOD) expresses the relationship between hernia and abdominal volume, and is used
      to predict operative difficulty and success. This systematic review assessed
      whether different definitions of LOD are used in the literature. The PubMed
      database was searched for articles reporting large hernia repairs that explicitly
      described LOD. Two reviewers screened citations and extracted data from selected
      articles, focusing on the definitions used for LOD, study demographics, study
      design, and reporting surgical specialty. One hundred and seven articles were
      identified, 93 full-texts examined, and 77 were included in the systematic
      review. Sixty-seven articles were from the primary literature, and 10 articles
      were from the secondary literature. Twenty-eight articles (36%) gave a written
      definition for loss of domain. These varied and divided into six broad groupings;
      four described the loss of the right of domain, six described abdominal strap
      muscle contraction, five described the "second abdomen", five describing large
      irreducible hernias. Six gave miscellaneous definitions. Two articles gave
      multiple definitions. Twenty articles (26%) gave volumetric definitions; eight
      used the Tanaka method [hernia sac volume (HSV)/abdominal cavity volume] and five
      used the Sabbagh method [(HSV)/total peritoneal volume]. The definitions used for
      loss of domain were not dependent on the reporting specialty. Our systematic
      review revealed that multiple definitions of loss of domain are being used. These
      vary and are not interchangeable. Expert consensus on this matter is necessary to
      standardise this important concept for hernia surgeons.

PMID- 30187091
TI  - Parasagittal vertex clots on head CT in infants with subdural hemorrhage as a
      predictor for abusive head trauma.
AB  - BACKGROUND: Abusive head trauma (AHT) is the most common cause of subdural
      hemorrhage (SDH) in infants younger than 12 months old. Clot formation in the
      parasagittal vertex seen on imaging has been associated with SDH due to AHT.
      There have been very few studies regarding these findings; to our knowledge, no
      studies including controls have been performed. OBJECTIVE: To describe
      parasagittal vertex clots on head computed tomography (CT) in infants with SDH
      and AHT compared to patients with SDH and accidental trauma, and to evaluate for
      parasagittal vertex clots in the absence of SDH in the setting of known
      accidental head trauma. MATERIALS AND METHODS: All infants younger than 12 months
      old with SDH present on CT scan were retrospectively identified from 2004 to
      2014. Blinded, independent review of all CT scans for clot formation at the
      parasagittal vertex was performed by a pediatric neuroradiologist. RESULTS:
      Ninety-nine patients were eligible for analysis. Mean age was 4 months. Fifty
      seven (57.6%) were male. Fifty-five (55.6%) patients were identified as having
      AHT and 22 (22.2%) had accidental trauma. Forty-five (81.2%) patients with AHT
      had parasagittal vertex clots present on CT scan compared to 8 (36.4%) patients
      with accidental trauma. Compared to patients without parasagittal vertex clots,
      those with parasagittal vertex clots were more likely to have AHT (66.2% vs.
      32.3%, P=0.001), no known mechanism of injury (69.1% vs. 32.3%, P=0.015), retinal
      hemorrhage (75% vs. 35.5%, P=0.002) and hypoxic-ischemic changes (25% vs. 0%,
      P=0.002). Patients with parasagittal vertex clots have eight times the odds of
      AHT compared to patients without parasagittal vertex clots. Age-matched control
      patients who underwent head CT scan due to a history of accidental head injury
      without SDH were identified (n=87); no patient in the control group had
      parasagittal vertex clots. CONCLUSION: The finding of parasagittal vertex clots
      on CT scans should raise suspicion for abuse and prompt further investigation,
      especially in the setting of no known, uncertain or inconsistent mechanism of
      injury.

PMID- 30187093
TI  - Methods of assessing and recording bladder sensation: a review of the literature.
AB  - INTRODUCTION AND HYPOTHESIS: The objective was to review different methods that
      have been used to assess bladder sensation and to provide an overview of the
      accuracy and objectivity of the measurement of the subjective perception of the
      bladder. METHODS: The MEDLINE and PubMed databases were searched to identify
      articles. References from those articles were also searched. Terms used for the
      search were: urinary bladder, sensation, cystometry, urodynamics, urinary
      incontinence and focus group. Eight hundred and fifty abstracts were identified
      from databases, and 12 from other sources. Twenty-two duplicate articles were
      removed. Irrelevant articles were excluded after reading their titles. Fifty-four
      articles were eligible, but 17 were excluded after reading the full text, leaving
      37 articles where assessment of bladder sensation was the main aim. RESULTS: Six
      different methods of measuring bladder sensation have been described in the
      literature. Although the most frequently used was cystometry, this is an invasive
      tool and does not reproduce bladder behaviour during daily life because it
      records bladder sensation as episodic events. The visual analogue scale using a
      forced diuresis protocol seemed to be an excellent tool. It was non-invasive and
      evaluated bladder sensation continuously, from an empty to a full bladder.
      CONCLUSIONS: In some of the studies, the samples were too small to draw any
      significant conclusions. There were also conflicting data on which tool was the
      most accurate, especially as each method of evaluating bladder sensation may
      influence the way it is described by participants.

PMID- 30187092
TI  - Histopathological Evaluation of Combined Impacts of the Synthetic Progestin
      Levonorgestrel and Temperature on the Female Zebrafish Maturation Using a Semi
      quantitative Grading Analysis-Is it Enough?
AB  - Pharmaceuticals contamination (e.g., synthetic progestins), and global climate
      change, represent two of the most stressful factors affecting aquatic species. To
      our knowledge, there is huge gap of data regarding the combined effects of both
      stressors on vertebrates' reproduction. Thus, it is crucial to implement rapid
      screenings of measurable histopathological alterations in fish gonads. For that,
      we propose: (1) an evaluation of the combined effects of progestin
      (levonorgestrel) and temperature on maturation of zebrafish female gonads, using
      a semi-quantitative method (i.e., grading) and (2) testing the robustness of the
      grading analysis comparatively to a quantitative method (i.e., stereology).
      Grading analysis showed a decrease on maturation stage of ovaries exposed to both
      stressors. Although grading is less robust than stereological analysis, it is
      recommended for a preliminary approach, since it gives a correct idea on trends
      and it is fast and cost-effective. For a detailed histological assessment, we
      recommend a stereological study.

PMID- 30187094
TI  - Evaluation of the interactions between the marine bacterium Pseudomonas
      fluorescens and the microalga Isochrysis galbana in simulated ballast tank
      environment.
AB  - To evaluate the impacts of the interaction between bacteria and microalgae has
      been the object of study by many research groups around the world. However,
      little is known about the interference that pigments produced by bacteria, such
      as the pyoverdine siderophore, can cause to microalgae like Isochrysis galbana.
      Pyoverdine is a fluorochrome produced by certain Pseudomonas strains, such as P.
      fluorescens, which plays a role in capturing and transporting iron ions from the
      environment to the cell. Unlike the oceans where Fe concentrations are extremely
      low (< 10-15 uM), in a ballast tank it is expected that there is a great supply
      of iron to the cells and that the absence of light is the main limiting factor
      until the water is discarded. Interestingly, under certain conditions, bacteria
      such as P. fluorescens absorb most of the water soluble iron ions and prevent the
      growth of phytoplankton even if there is sufficient light. Changes in the
      patterns of light distribution in aquatic environments may affect the
      physiological characteristics of certain microalgae. This study aimed to evaluate
      the impacts of the presence of P. fluorescens on the survival and growth of I.
      galbana inside the tank. For the study, an experiment was carried out to study
      the interaction between P. fluorescens and I. galbana under simulated conditions
      of a vessel in the presence/absence of Pseudomonas and light. The results showed
      that the presence of the bacteria is not the main limiting factor for microalga
      growth. The effect of the light factor was determinant on the reproduction rate.
      It is believed that pyoverdine produced by P. fluorescens affected I. galbana
      stock either by increasing mortality or decreasing growth rate as revealed by
      laboratory experiments. However, it was not possible to check if the pigment
      concentration was affected by the growth of microalgae.

PMID- 30187095
TI  - Winogradskyella profunda sp. nov. isolated from the Chukchi Sea bottom sediments.
AB  - An aerobic, Gram-negative, yellow-pigmented non-motile rod-shaped bacterium,
      designated Ch38T, was isolated from a sediment sample collected from the Chukchi
      Sea in the Arctic Ocean. Comparative 16S rRNA gene sequence analysis positioned
      strain Ch38T into the genus Winogradskyella as a distinct line adjacent to
      Winogradskyella multivorans KCTC 23891T, sharing the highest similarities of
      97.5%, 97.2%, and 97.1% with Winogradskyella eximia KCTC 12219T, Winogradskyella
      damuponensis KCTC 23552T, and Winogradskyella multivorans KCTC 23891T,
      respectively. Strain Ch38T grew at 5-36  degrees C and in the presence of 1-6%
      (w/v) NaCl. It contained MK-6 as the predominant menaquinone and iso-C16:0 3-OH,
      anteiso-C15:0 followed by iso-C15:0 and iso-C16:1 as the major fatty acids. Polar
      lipids consisted of phosphatidylethanolamine, three unknown aminolipids, an
      unknown lipid and an unknown phospholipid. The DNA C + C content was 31.7 mol%.
      Based on the phylogenetic analysis and distinctive phenotypic characteristics,
      strain Ch38T is concluded to represent a novel species of the genus
      Winogradskyella, for which the name Winogradskyella profunda sp. nov. is
      proposed. The type strain of the species is strain Ch38T (= KMM 9725T = KACC
      19710T).

PMID- 30187096
TI  - Blood loss and allogeneic transfusion for surgical treatment of periprosthetic
      joint infection: a comparison of one- vs. two-stage exchange total hip
      arthroplasty.
AB  - PURPOSE: The purpose of the current study was to compare the blood loss and the
      need for allogeneic transfusion after one- and two-stage exchange arthroplasty
      for periprosthetic joint infection (PJI) of THA. METHODS: We performed a
      retrospective review of all patients undergoing either one-stage or two-stage
      septic exchange arthroplasty at two high-volume infection referral centres. The
      study cohort consists of 90 patients undergoing the two-stage and 184 patients
      the one-stage exchange arthroplasty. The difference between pre- and post
      operative haemoglobin (Hb) and total blood loss as well as the allogeneic
      transfusion rate were compared between both groups. RESULTS: Both procedures
      together of the two-stage septic exchange arthroplasty had higher intra-operative
      blood loss and allogeneic blood transfusion rate compared to the one-stage septic
      exchange arthroplasty group. However, among the patients of the two-stage group,
      there were more smokers and had worse physical status (ASA) and higher mortality
      risk (CCI) than patients in the one-stage group. CONCLUSIONS: Two-stage septic
      revision of total hip arthroplasty has higher rates of blood loss and transfusion
      rates than one-stage revision. Therefore, the authors believe that blood loss
      rate, including its complications, should be considered when decision for the
      type of staged septic exchange is made.

PMID- 30187097
TI  - Letter to the editor concerning the article: "Intra-articular injection of
      autologous adipose-derived stromal vascular fractions for knee osteoarthritis: a
      double-blind randomized self-controlled trial" (Hong et al. International
      Orthopaedics doi: 10.1007/s00264-018-4099-0).

PMID- 30187098
TI  - Total hip arthroplasty with a monoblock conical stem and subtrochanteric
      transverse shortening osteotomy in Crowe type IV dysplastic hips.
AB  - PURPOSE: This series assessed the clinical and radiographic outcomes of total hip
      arthroplasty (THA) with femoral shortening osteotomy for the management of
      patients with Crowe type IV hip dysplasia. METHODS: Only patients with Crowe type
      IV hip dysplasia who underwent primary THA combined with a subtrochanteric
      transverse osteotomy with an uncemented monoblock conical stem were included. The
      clinical and radiographic evaluations were performed before and immediately after
      surgery, and at last follow-up. The hip function was assessed with the Harris Hip
      Score (HHS). RESULTS: Seventy-four patients (102 hips) with a mean age of 53.9
      (range, 20-83) were evaluated at an average follow-up of 11.3 years (range, 5
      25). Stem revision occurred in two (1.9%) cases, with a survivorship of 95.9%
      (95%IC, 91.9-99.9%) at ten years. The average HHS increased from 44 (range, 15
      78) pre-operatively to 90.3 (range, 62-100) at last follow-up (p < 0.001).
      Osteotomy site non-union and early dislocation were observed in 3.9 and 3.8%,
      respectively. No cases of nerve palsy were reported. CONCLUSIONS: THA with a
      monoblock conical stem associated with subtrochanteric transverse osteotomy
      provides good long-term survival, clinical and radiographic results. It may be
      considered an effective management of patients with Crowe IV hip dysplasia.

PMID- 30187099
TI  - Surgical approach for open reduction and internal fixation of clavicle fractures:
      a comparison of vertical and horizontal incisions.
AB  - PURPOSE: This study was designed to compare the results of clavicle fracture open
      reduction internal fixation (ORIF) with standard horizontal incision versus
      vertical incision. METHODS: ORIF surgery performed between October 2012 and
      August 2016 was included. The surgical approach was chosen according to surgeon
      preference as vertical or horizontal. Functional outcomes, fracture union,
      complications, scar appearance, skin irritation, and denervation around the scar
      were assessed at a minimum follow-up of three months. RESULTS: Thirty-eight
      patients, age 39 +/- 12 years, were operated upon, 22 through vertical incisions
      and 16 through horizontal incisions. There were no significant group differences
      in functional scores, fracture union, or complications. Two patients in the
      vertical incision group had a post-operative haematoma. The scar length was
      significantly shorter when a vertical incision was used (6.75 +/- 1.25 cm vs 8.9
      +/- 2.3 cm, P = 0.001). The typical distribution of hypoesthetic skin area distal
      and lateral to the scar represented iatrogenic damage to the supraclavicular
      nerves and was found in 66% of patients. The mean hypoesthetic surface area was
      smaller in the vertical incision group (38 +/- 29 cm2 vs 48 +/- 28 cm2, P = non
      significant). CONCLUSION: Vertical incision results in shorter scars but may be
      associated with increased incidence of haematomas. Meticulous closure of the
      subcutaneous tissue is recommended.

PMID- 30187100
TI  - Small P particles formed by the Taiwan-native norovirus P domain overexpressed in
      Komagataella pastoris.
AB  - The protrusion (P) domain of the major structural protein VP1 of norovirus (NoV)
      is critical for the host's immune response and receptor binding. Most
      heterologous P domains expressed in Escherichia coli or Komagataella pastoris
      (formally known as Pichia pastoris) form P particles consisting of 24 P monomers
      formed through intermolecular contact in the P regions and an end-linked cysteine
      tag. The small P particle is only found in P domains with terminal modifications.
      In this study, the NoV P domain of the most predominant NoV strain GII.4 isolated
      from Taiwan was expressed in K. pastoris. A high yield of NoV P was obtained
      using the high-cell density fermentation process in K. pastoris. A large amount
      of the small P particles and the trimer and dimer complexes formed by 12, 6, and
      2 P monomers were observed in both the expression of the NoV P-His and P
      containing cysteine tag at the N-terminus. Dynamic light scattering and
      transmission electron microscopy analysis of the purified NoV P-His and P
      revealed that most of these small P particles are triangle-, square-, and ring
      shaped with a diameter of 14-15 nm. The binding ability of purified NoV P-His and
      P to human histo-blood group antigen was confirmed by a saliva-binding assay.
      Without terminal modification, small P particles were formed in our study. The
      amino acid sequence analysis showed only four different amino acids (residue 84,
      119, 136, and 313) between the P domain in this study and other investigated
      GII.4 strains suggesting that these amino acids might play an important role in
      the P particle formation. The small P particles formed by the Taiwan-native
      norovirus P domain overexpressed in K. pastoris may provide further information
      for morphogenesis studies and vaccine development.

PMID- 30187101
TI  - Marine-derived Phoma-the gold mine of bioactive compounds.
AB  - The genus Phoma contains several species ubiquitously present in soil, water, and
      environment. There are two major groups of Phoma, viz., terrestrial and marine.
      After 1981 researchers all over the world have focused on marine-derived Phoma
      for their bioactive compounds. The marine Phoma are very rich sources for novel
      bioactive secondary metabolites, which could potentially be used as drugs.
      Recently, a large number of structurally unique metabolites with potential
      biological and pharmacological activities have been isolated from the marine
      Phoma species particularly Phoma herbarum, P. sorghina, and P. tropica. These
      metabolites mainly include diterpenes, enolides, lactones, quinine, phthalate,
      and anthraquinone. Most of these compounds possess antimicrobial, anticancer,
      radical scavenging, and cytotoxic properties. The present review has been focused
      on the general background of Phoma, current approaches used for its
      identification and their limitations, difference between terrestrial and marine
      Phoma species. In addition, this review summarizes the novel bioactive compounds
      derived from marine Phoma and their biological activities.

PMID- 30187102
TI  - Enhanced enzymatic hydrolysis of wheat straw by two-step pretreatment combining
      alkalization and adsorption.
AB  - Wheat straws (WS) were pretreated by a two-step pretreatment for enhanced
      enzymatic hydrolysis. The raw wheat straw (RWS) was firstly soaked in microwave
      assisted NaOH solution at the presence of a mixed solution of H2O2 and hexadecyl
      trimethyl ammonium chloride (HTAC), and the residue was put into methyl orange
      (MO) solution to obtain the final substrate for enzymatic hydrolysis. It was
      interesting to find that the WS after the first step of the pretreatment could
      effectively remove MO in the second step of the pretreatment with the highest
      removal efficiency of 98.86% at the MO concentration of 25 mg/L and at the
      adsorbent-adsorbate ratio of 0.8%. Meanwhile, the enzymatic hydrolysis efficiency
      of the WS that was pretreated by the two steps was higher than that of the RWS as
      well as the first-step-pretreated WS. Enzymatic hydrolysis experiment showed that
      the glucose concentration after 48-h hydrolysis was 4.85 g/L at the solid loading
      of 5%, compared with the RWS of 0.90 g/L and the first-step-pretreated WS of 4.33
      g/L. This suggested that the two-step pretreatment method could not only make WS
      as a good adsorbent but also a more biodegradable lignocellulosic material.
      Characterization analysis showed that the specific surface area and the cellulose
      content of the WS were both increased after the two-step pretreatment, indicating
      that the pretreatment method was significant to properly utilizing WS as
      biosorbent and biofuel. Besides, a possible mechanism for the effect of the
      pretreatment on the WS was proposed.

PMID- 30187103
TI  - Regulation of biosimilar medicines and current perspectives on interchangeability
      and policy.
AB  - Competition arising from the increasing availability of biosimilar medicines has
      resulted in healthcare savings and has provided greater patient access to high
      cost therapeutics in Europe. The biosimilar market in the USA is relatively new
      so the full impact of biosimilar availability remains to be seen. Educational
      initiatives relating to the use of biosimilar medicines are currently being
      undertaken by regulators, policy makers and industry. The debate on biosimilars
      has moved on from the appropriateness of the regulatory framework which governs
      their approval, to the practice of interchangeability. Interchangeability is an
      important issue for healthcare professionals but different definitions and
      regulatory frameworks exist in the USA and Europe. In the USA, an interchangeable
      biological product is a biosimilar which may be substituted by a pharmacist,
      subject to local State policies. The interchangeability of a biosimilar with its
      reference medicine will be evaluated by the United States Food and Drug
      Administration (FDA) in cases where approval as an 'interchangeable product' is
      sought. In contrast, the European Medicines Agency (EMA) does not assess or make
      recommendations on interchangeability, therefore, in Europe, interchangeability
      does not mean substitution but is generally physician-led or driven by national
      policy. This paper provides an overview of the regulation of biosimilar
      medicines. Challenges associated with the demonstration of interchangeability and
      practical considerations relating to switching are also discussed. Finally, we
      present policies that have been adopted to date in several European countries,
      the USA and Australia, which aim to promote the use of biosimilar medicines.

PMID- 30187104
TI  - Pretreatment PET/CT imaging of angiogenesis based on 18F-RGD tracer uptake may
      predict antiangiogenic response.
AB  - PURPOSE: To explore the relationship between metabolic uptake of the 18F-ALF-NOTA
      PRGD2 (18F-RGD) tracer on positron emission tomography/computerized tomography
      (PET/CT) and the antiangiogenic effect of apatinib in patients with solid
      malignancies. MATERIALS AND PATIENTS: Patients with measurable lesions scheduled
      for second- or third-line single-agent therapy with apatinib were eligible for
      this prospective clinical trial. All patients underwent 18F-RGD PET/CT
      examination before the start of treatment. Standardized uptake values (SUVs) of
      contoured tumor lesions were computed and compared using independent sample t
      tests or the Mann-Whitney U test. Receiver-operating characteristic (ROC) curve
      analysis was used to determine accuracy in predicting response. Survival curves
      were compared using the Kaplan-Meier method. RESULTS: Of 38 patients who
      consented to study participation, 25 patients with 42 measurable lesions met the
      criteria for inclusion in this response assessment analysis. The median follow-up
      time was 3 months (range, 1-10 months), and the median progression-free survival
      (PFS) was 3 months (95% confidence interval, 1.04-4.96). The SUVpeak and SUVmean
      were significantly higher in responding tumors than in non-responding tumors
      (4.98 +/- 2.34 vs 3.59 +/- 1.44, p = 0.048; 3.71 +/- 1.15 vs 2.95 +/- 0.49, P =
      0.036). SUVmax did not differ between responding tumors and non-responding tumors
      (6.58 +/- 3.33 vs 4.74 +/- 1.83, P = 0.078). An exploratory ROC curve analysis
      indicated that SUVmean [area under the ROC curve (AUC) = 0.700] was a better
      parameter than SUVpeak (AUC = 0.689) for predicting response. Using a threshold
      value of 3.82, high SUVmean at baseline was associated with improved PFS (5.0 vs.
      3.4 months, log-rank P = 0.036). CONCLUSION: 18F-RGD uptake on PET/CT imaging
      pretreatment may predict the response to antiangiogenic therapy, with higher 18F
      RGD uptake in tumors predicting a better response to apatinib therapy.

PMID- 30187106
TI  - [Aortic aneurysm and EVAR - an update].

PMID- 30187105
TI  - 18F-FDG PET/CT is useful for determining survival outcomes of patients with
      multiple myeloma classified as stage II and III with the Revised International
      Staging System.
AB  - PURPOSE: This study evaluated the prognostic role of 18F-FDG PET/CT at baseline
      in patients with newly diagnosed multiple myeloa (MM) and evaluated the
      prognostic relevance of 18F-FDG PET/CT for each stage according to the Revised
      International Staging System (R-ISS). METHOD: We retrospectively analyzed the
      records of 167 patients with newly diagnosed MM. 18F-FDG PET/CT was performed
      prior to induction therapy in patients with newly diagnosed MM. RESULTS: In the
      total cohort, the presence of more than three hypermetabolic focal lesions (FLs)
      or extramedullary disease (EMD) on baseline PET/CT was associated with
      significantly inferior progression-free survival (PFS) and overall survival (OS)
      than other patients. Because most patients (91%) with EMD had more than three
      FLs, PET/CT positivity was defined as the presence of more than three FLs or the
      presence of EMD. In multivariate analyses, PET/CT positivity was an independent
      predictor of PFS and OS in all patients. Fifty-five patients (46.1%) with R-ISS
      II were PET/CT-positive at baseline and had significantly shorter PFS and OS.
      PET/CT positivity was also correlated with poor PFS and OS in patients with R-ISS
      III. CONCLUSION: 18F-FDG PET/CT was an independent predictor of survival outcomes
      in patients with newly diagnosed MM. In addition, performing 18F- FDG PET/CT at
      diagnosis may be useful for determining the survival outcomes of MM patients with
      R-ISS II and III.

PMID- 30187109
TI  - Correction to: Osteitis: a retrospective feasibility study comparing single
      source dual-energy CT to MRI in selected patients with suspected acute gout.
AB  - The name of Kay Geert A. Hermann is incorrectly captured in the original article
      and is now corrected in this paper.

PMID- 30187108
TI  - Higher habitual dietary caffeine consumption is related to lower experimental
      pain sensitivity in a community-based sample.
AB  - RATIONALE: Caffeine is the most widely consumed psychoactive substance in the
      world. Caffeine administered acutely in a laboratory environment or as a
      medication adjuvant has known properties that help alleviate pain. However, much
      less is known about the potential impact of habitual dietary caffeine consumption
      on the experience of pain. OBJECTIVES: The primary objective of this
      observational study was to determine whether caffeine consumed habitually as part
      of a daily diet was associated with experimental pain sensitivity using noxious
      stimuli in a non-clinical sample of 62 community-dwelling adults between 19 and
      77 years old. METHODS: Study participants monitored their daily dietary caffeine
      consumption (e.g., coffee, tea, soda, energy drinks, and chocolate) across a
      period of seven consecutive days using a caffeine consumption diary. On the
      seventh day of caffeine consumption monitoring, participants presented to the
      laboratory to complete experimental pain sensitivity testing. Noxious thermal and
      mechanical stimuli were used to obtain threshold and tolerance for painful heat
      and pressure, respectively. RESULTS: Data analysis revealed that greater self
      reported daily caffeine consumption was significantly associated with higher heat
      pain threshold (beta = .296, p = .038), higher heat pain tolerance (beta = .242,
      p = .046), and higher pressure pain threshold (beta = .277, p = .049) in multiple
      regression models adjusted for covariates. CONCLUSIONS: Results of this study
      completed with community-dwelling adults revealed that individuals who habitually
      consume greater amounts of caffeine as part of their daily diets demonstrate
      diminished sensitivity to painful stimuli in a laboratory setting.

PMID- 30187110
TI  - High-resolution ultrasound in the assessment of the distal biceps brachii
      tendinous complex.
AB  - OBJECTIVE: To establish a high-resolution US technique that enables a systematic
      morphometric examination of the three components that form the distal biceps
      brachii tendinous complex; the internal bicipital aponeurosis, the distal biceps
      brachii tendon and the external bicipital aponeurosis (also known as lacertus
      fibrosus). MATERIALS AND METHODS: Fifty cryopreserved cadaver body donor elbows
      were dissected to obtain morphometric reference values and to establish reliable
      landmarks for the US examination. Then, a systematic US technique was designed
      and validated by a one-to-one US/dissection analysis of 11 cryopreserved cadaver
      body donor elbows. Finally, the systematic US technique was carried out in 44
      healthy volunteers and morphometric parameters were compared to those obtained in
      the first part of the study. RESULTS: Mean dissection reference values: internal
      bicipital aponeurosis width 39.61 mm (10.02 SD) and thickness 0.75 mm (0.24 SD),
      distal biceps brachii tendon width 8.38 mm (1.87 SD) and thickness 2.73 mm (0.69
      SD), external bicipital aponeurosis width 11.17 mm (5.84 SD) and thickness 0.85
      mm (0.28 SD). One-to-one US/dissection correlation was overall good (intraclass
      correlation coefficient 0.876, p < 0.0001). When comparing volunteer
      US/dissection measurements, significant differences were encountered in all
      measures except for internal bicipital aponeurosis width. However, the overall
      magnitude of such significant differences was < 0.7 mm. CONCLUSIONS: Using the
      systematics hereby proposed, high-resolution US is reliable for the morphometric
      assessment of the distal biceps brachii tendinous complex. The external bicipital
      aponeurosis is morphometrically the most variable structure.

PMID- 30187111
TI  - Calcified leiomyoma of the deltoid: pathophysiology and imaging review.
AB  - Leiomyomas are benign tumors of smooth muscle cells. Leiomyomas of somatic soft
      tissue are a specific class of leiomyoma believed to arise from the smooth muscle
      cells found in the walls of blood vessels and represent less than 4% of benign,
      somatic soft tissue tumors. Of the somatic soft tissue tumors, approximately one
      third will become calcified. We report an intramuscular, calcified leiomyoma
      arising from the left deltoid of a 47-year-old Caucasian male. To the best of the
      authors' knowledge, this is the first reported case of a calcified, intramuscular
      leiomyoma of the deltoid. Imaging studies and patient presentation were initially
      suggestive of tumoral calcinosis or myositis ossificans. It was not until
      pathologic examination that the correct diagnosis of the calcified leiomyoma was
      made. Leiomyoma should be included in the differential diagnosis of calcified
      soft tissue masses. If excised with adequate margins, recurrence is unlikely.

PMID- 30187112
TI  - Impaired residual renal function predicts denosumab-induced serum calcium
      decrement as well as increment of bone mineral density in non-severe renal
      insufficiency.
AB  - : Denosumab treatment of osteoporotic patients, except those with severe renal
      insufficiency, reduced cCa levels. Low baseline cCa, low estimated glomerular
      filtration rate, and high bone turnover increased the risk of lower cCa, while
      increasing bone mineral density. Pretreatment with antiresorptive agents was
      beneficial in reducing the risk of hypocalcemia. INTRODUCTION: Although denosumab
      induced hypocalcemia has been frequently observed in patients with chronic kidney
      disease (CKD) stages 4-5D being treated with denosumab for osteoporosis, few
      studies have assessed the risk factors for serum-corrected calcium (cCa)
      reductions in patients with non-severe renal insufficiency. This study assessed
      the risk factors for reduced cCa concentration following denosumab administration
      and analyzed factors predictive of changes in bone mineral density (BMD).
      METHODS: Seventy-seven osteoporotic patients, not including those with CKD stages
      4-5D, were treated with 60 mg denosumab once every 6 months. Biochemical
      parameters and BMD were analyzed from prior to the initial dose until 1 month
      after the second dose. RESULTS: Following the first administration of denosumab,
      cCa levels decreased, reaching a minimum on day 7. Multiple linear regression
      analyses showed that baseline cCa, estimated glomerular filtration rate (eGFR) <
      60 mL/min/1.73 m2, tartrate-resistant acid phosphatase-5b (TRACP-5b), and bone
      alkaline phosphatase (BAP) or pretreatment with antiresorptive agents were
      significant factors independently associated with the absolute reduction in cCa
      from baseline to day 7 (DeltacCa0-7 days). DeltacCa0-7 days after the second dose
      of denosumab was significantly lower than that after the first dose. After 6
      months of denosumab treatment, both LS-BMD and FN-BMD significantly increased
      from baseline. LS-BMD and FN-BMD correlated significantly with baseline TRACP-5b
      or BAP and eGFR, respectively. CONCLUSIONS: Both low eGFR and high bone turnover
      were independent risk factors for denosumab-induced cCa decrement, and for
      increases in BMD. Pretreatment with antiresorptive agents may reduce the risk of
      hypocalcemia.

PMID- 30187113
TI  - Focus on acute kidney injury 2017.

PMID- 30187114
TI  - [Treatment of malignant pleural mesothelioma: American Society of Clinical
      Oncology Clinical Practice Guideline].

PMID- 30187115
TI  - Children's behavior and spontaneous talk in a future thinking task.
AB  - We explored 3-, 4-, and 5-year-olds' (N = 120) "explicit" and "spontaneous"
      future-oriented cognition. Specifically, children had to think ahead to meet a
      future physiological need (desire for food) or psychological need (avoiding
      boredom). One group of children alternated between a room with candy and a room
      without candy, spending 3 min per visit. Children were explicitly asked which
      room they wanted to put extra candy in for a future visit to the lab (correct
      answer: room without candy). A second group of children underwent the same
      procedure but with toys as the resource instead of food (a replication of Atance
      et al. in J Exp Child Psychol 129:98-109, 2015). In the food condition, 3-, 4-,
      and 5-year-olds all placed candy in the correct room above chance, but only 4-
      and 5-year-olds were above chance in the toy condition. Overall, 4- and 5-year
      olds outperformed 3-year-olds, and children performed better in the food
      condition than the toy condition. Children's spontaneous (or "involuntary")
      future thinking was assessed by coding their utterances while in the two rooms.
      Children who solved the explicit task uttered more task-relevant future and past
      statements than children who failed. Examining spontaneous talk also allowed us
      to explore children's spontaneous "solving" of the task before being asked an
      explicit test question. This research highlights the importance of varying
      stimuli in future thinking tasks and developing methods to capture
      spontaneous/involuntary future thinking in young children.

PMID- 30187117
TI  - Carotid stiffness and atherosclerotic risk: non-invasive quantification with
      ultrafast ultrasound pulse wave velocity.
AB  - OBJECTIVES: To evaluate the value of ultrafast pulse wave velocity (ufPWV) for
      the quantitative assessment of carotid stiffness and its associated with
      atherosclerosis (AS) risk. METHODS: The present study included 233 patients with
      hyperlipoidaemia (AS risk group) and 114 healthy adults as the control group. The
      carotid (n = 694) intima-media thickness (cIMT), pulse wave velocity-beginning of
      systole (PWV-BS) and pulse wave velocity-end of systole (PWV-ES) were measured on
      sample images. Differences, distributive characteristics and correlation
      evaluation were assessed in patients (ages 18-29, 30-39, 40-49, 50-59, 60-69 and
      >=70) and carotids (control group vs AS risk group). RESULTS: The cIMT, PWV-BS
      and PWV-ES increased with age; PWV-ES and cIMT showed an early significant
      increase in the 30-39 years group, whereas PWV-BS displayed a significant
      increase at 40-49 years compared with the 18- to 29-years group. Besides, PWV-ES
      correlated well with age compared with PWV-BS and cIMT. For carotid level, cIMT,
      PWV-BS and PWV-ES measurements were higher in the AS risk group compared with
      control. To compare the value of ufPWV and cIMT in early AS assessment, we
      subdivided groups into cIMT subgroups using a cut-off thickness of 0.050 cm. PWV
      ES measurements were higher in the AS risk group compared with the control in the
      0.040-0.050 cm (not thickened) and 0.051-0.060 cm (thickened) cIMT subgroups.
      CONCLUSIONS: Carotid ufPWV measurement at PWV-ES is a novel modality for the
      early diagnosis and quantitative assessment of arterial stiffness associated with
      atherosclerotic risk. KEY POINTS: * ufPWV technique is real-time and well
      repeatable for assessing carotid stiffness * ufPWV measurements increase and
      correlate well with age * PWV-ES is a quantitative predictor for the early
      assessment of AS.

PMID- 30187116
TI  - Rodents, not birds, dominate predation-related ecosystem services and disservices
      in vertebrate communities of agricultural landscapes.
AB  - To understand the relationship between conservation measures and agricultural
      yields, we need to know the contributions of organisms to both ecosystem services
      and disservices. We studied the activity and contribution of birds and mammals to
      intermediate ecosystem services (predation of weed seeds or invertebrate pests)
      and disservices (predation of crop seeds or beneficial invertebrates) in southern
      Sweden between June and November 2016. We measured seed and invertebrate
      predation rates using trays placed in front of 32 wildlife cameras in 16 cereal
      fields with a local habitat contrast (8 fields adjacent to another crop field and
      8 fields adjacent to a semi-natural grassland) and along a landscape
      heterogeneity gradient (amount of semi-natural grassland). Both activity and
      predation were dominated by small mammals (mainly rodents), yet only a few
      species contributed to predation services and disservices according to camera
      records. Small mammal activity and predation varied considerably over time. Small
      mammal activity was significantly higher at trays with crop seeds or beneficial
      invertebrate prey compared to trays with pest prey, and crop seed predation by
      small mammals was significantly higher than weed seed predation. In contrast,
      bird activity and predation did not differ significantly between resource types,
      but varied over time depending on the habitat contrast. Predation of animal prey
      by birds was highest after cereal harvest, independent of habitat contrast. Our
      study highlights that birds and in particular rodents provide important
      intermediate ecosystem services, but also disservices, which fluctuate strongly
      in intensity over time.

PMID- 30187118
TI  - Microbubble contrast enhancement of neointima after drug-eluting stent
      implantation: an optical coherence tomography study.
AB  - Microvessels within neoatherosclerosis are associated with vulnerability and
      increase from the early to the very late phase after drug-eluting stent
      implantation. Microbubble contrast agents have been suggested to enhance tissue
      microvasculature for optical coherence tomography (OCT) imaging. The present
      study investigated whether OCT signal intensity of neointima within stented
      segments was enhanced after intracoronary administration of microbubble contrast
      agents. A total of 40 patients who underwent follow-up coronary angiography after
      drug-eluting stent implantation were enrolled. At the time of follow-up coronary
      angiography, OCT images of the stented segments were recorded before and after
      intracoronary administration of microbubble contrast agents. Mean OCT signal
      intensity of neointima after microbubble administration significantly increased
      [95.5 (85.7, 106.2) vs. 96.5 (88.7, 109.9), p = 0.001]. Multivariate analysis
      demonstrated the relationship between diabetes and greater neointima enhancement.
      The change in the OCT signal intensity of neointima following microbubble
      administration tended to be higher in diabetic patients than in non-diabetic
      patients [4.6 (0.6, 8.5) vs. 1.4 (- 1.1, 3.0), p = 0.05]. These findings suggest
      that this methodology may allow identification of neovascularization in neointima
      and evaluation of vulnerability of neoatherosclerosis. Microvessels in neointima
      may be a future target of pharmacological and interventional innovations for
      preventing stent failure.

PMID- 30187119
TI  - Right ventricular dysfunction is associated with exercise intolerance and poor
      prognosis in ischemic heart disease.
AB  - Right ventricular (RV) function is a prognostic factor in ischemic heart disease
      (IHD) patients, although its correlations with exercise capacity and cardiac
      rehabilitation (CR) efficacy are unknown. We aimed to clarify how RV function was
      associated with exercise tolerance and efficacy of phase II CR in IHD patients.
      We retrospectively analyzed 301 consecutive IHD patients who underwent phase II
      CR. We defined RV dysfunction using a combination of RV fractional area change <
      35%, tricuspid annular plane systolic excursion < 1.6 cm, and systolic velocity <
      10 cm/s. Exercise capacity was assessed using cardiopulmonary testing. The
      relation between RV function and exercise capacity was analyzed. The all-cause
      death and major adverse cardiac events (MACE) were evaluated by survival curve.
      The RV dysfunction group (n = 121) showed impaired left ventricular (LV) systolic
      and diastolic function before CR contrary to the normal RV function group (n =
      180). The presence of RV dysfunction significantly reduced %AT by 4% and
      %Peak[Formula: see text] by 9% before CR, but increases the degree of improvement
      in %Peak[Formula: see text] with CR, independent of LV systolic and diastolic
      function. Univariate analysis demonstrated that previous coronary artery bypass
      grafting (CABG) was negatively associated with all-cause deaths and MACE.
      Adjusted for previous CABG, poor prognosis correlated with coexisting LV and RV
      dysfunction (hazard ratio [HR] 3.91, 95% confidence interval [CI] 1.13-13.53, P =
      0.03) and RV dysfunction alone (HR 3.08, 95% CI 1.01-9.37, P = 0.05). In IHD
      patients, RV dysfunction is associated with exercise intolerance before CR and
      increased MACE risk, independent of LV function. The CR was effective in patients
      with RV dysfunction.

PMID- 30187120
TI  - Inconsistencies in the management of neonates born to mothers with "thyroid
      diseases".
AB  - Although thyroid medications are frequently prescribed during pregnancy,
      paediatricians treating the respective neonates often have no information about
      the underlying maternal thyroid disease, and inconsistencies in postnatal
      diagnostics may result. We analysed a cohort of 1819 mothers admitted for
      delivery in 1 year to one hospital. We analysed the pre- and postpartum
      diagnostics in the mothers, the postnatal diagnostics in the neonates and their
      postnatal auxological development. Two hundred thirteen mothers (11.7%) had
      "thyroid disease"; 37 (2.0%) had Hashimoto thyroiditis, seven (0.4%) Graves'
      disease and 169 (9.3%) "thyroid disease of other origins". One hundred eighty
      eight out of 213 (88%, 10.3% of the entire cohort) took levothyroxine. Pre- and
      postpartum diagnostics of the mothers and postnatal diagnostics of the neonates
      revealed striking inconsistencies. For example, 39 % of the gynaecologists
      routinely determined TSH, while only 59% carried out a dosage adjustment for
      known hypothyroidism. Second specialists were consulted in 86%. Unnecessary
      postpartum diagnostics were initiated in 19/213 neonates (9%). TRAb was analysed,
      however, in only one neonate born from the mothers with Graves' disease-a
      condition in which further diagnostic efforts are mandatory.Conclusion: Although
      many pregnant women have thyroid dysfunction, we observed a lack of uniformity in
      the diagnostic approach of the women and their neonates. What is Known: *
      Disturbed maternal thyroid function in pregnancy often has an adverse impact on
      both the mother and the foetus. * Although detailed guidelines for managing
      impaired maternal thyroid function during pregnancy have been published, their
      application in clinical practice varies widely. What is New: * Recommendations
      for managing the newborn of a mother presenting with thyroid disease of unknown
      entity are remarkably inconsistent. * This leads to a possible over-diagnosis in
      general and a potentially life-threatening failure to note neonatal
      hyperthyroidism requiring rapid treatment.

PMID- 30187121
TI  - Distribution of EGFR amplification, combined chromosome 7 gain and chromosome 10
      loss, and TERT promoter mutation in brain tumors and their potential for the
      reclassification of IDHwt astrocytoma to glioblastoma.
AB  - EGFR amplification (EGFRamp), the combination of gain of chromosome 7 and loss of
      chromosome 10 (7+/10-), and TERT promoter mutation (pTERTmut) are alterations
      frequently observed in adult IDH-wild-type (IDHwt) glioblastoma (GBM). In the
      absence of endothelial proliferation and/or necrosis, these alterations currently
      are considered to serve as a surrogate for upgrading IDHwt diffuse or anaplastic
      astrocytoma to GBM. Here, we set out to determine the distribution of EGFRamp,
      7+/10-, and pTERTmut by analyzing high-resolution copy-number profiles and next
      generation sequencing data of primary brain tumors. In addition, we addressed the
      question whether combinations of partial gains on chromosome 7 and partial losses
      on chromosome 10 exhibited a diagnostic and prognostic value similar to that of
      complete 7+/10-. Several such combinations proved relevant and were combined as
      the 7/10 signature. Our results demonstrate that EGFRamp and the 7/10 signature
      are closely associated with IDHwt GBM. In contrast, pTERTmut is less specific for
      IDHwt GBM. We conclude that, in the absence of endothelial proliferation and/or
      necrosis, the detection of EGFRamp is a very strong surrogate marker for the
      diagnosis of GBM in IDHwt diffuse astrocytic tumors. The 7/10 signature is also a
      strong surrogate marker. However, care should be taken to exclude pleomorphic
      xanthoastrocytoma. pTERTmut is less restricted to this entity and needs companion
      analysis by other molecular markers to serve as a surrogate for diagnosing IDHwt
      GBM. A combination of any two of EGFRamp, the 7/10 signature and pTERTmut, is
      highly specific for IDHwt GBM and the combination of all three alterations is
      frequent and exclusively seen in IDHwt GBM.

PMID- 30187123
TI  - Death by anaphylactic shock in an institution: an accident or negligence?
AB  - This is a description of a man, institutionalised for learning difficulties,
      known to have an allergy to seafood. After eating a pie, the patient quickly
      developed dyspnoea and vomiting. The staff at the institution administered
      epinephrine and called the emergency services. Despite cardiopulmonary
      resuscitation, the patient died shortly after being admitted to the emergency
      department of the University Hospitals of Geneva. In the light of the
      circumstances of the death and of a discrepancy between the information given to
      the police by the staff at the institution looking after the patient on the one
      hand, and the preliminary elements of the investigation on the other hand, it was
      suspected that there was failure in care of the patient and our institute was
      asked to carry out an autopsy. Basing on all the investigations carried out, the
      cause of death was anaphylactic reaction following the ingestion of seafood,
      contrary to what had been alleged by the staff at the home.

PMID- 30187122
TI  - Biogeography of arbuscular mycorrhizal fungi (Glomeromycota): a phylogenetic
      perspective on species distribution patterns.
AB  - Information on the biogeography of arbuscular mycorrhizal fungi (AMF) is
      important because this group of obligately symbiotic soil microbes is a
      ubiquitous and functionally critical component of terrestrial ecosystems. In this
      paper, we utilize a biogeography database summarizing data on AMF species
      distribution linked to geographic and environmental conditions to describe global
      distribution patterns and interpret these patterns within a phylogenetic
      perspective. The data were obtained from accessions in living culture collections
      (INVAM, CICG), species descriptions, and other published literature from 1960 to
      2012. The database contains 7105 records, 6396 of them from 768 published papers
      and the remaining 709 from culture accessions. Glomeromycotan species were
      recorded in all seven continents, 87 countries, 11 biogeographical realms, and 14
      biomes. The distribution of families differed among climatic zones and
      continents, but they, together with all genera, appear to be cosmopolitan.
      Distribution of AMF species shows a slight decrease from low to high latitudes,
      but this decrease is steeper in the southern than in the northern hemisphere. A
      total of 189 species is shared between ancient supercontinents Gondwana and
      Laurasia and 78 species are common to all climatic zones. Ninety-five species
      (43% of the total) have known cosmopolitan distribution, including members of all
      genera except Redeckera. Some species have disjunct distribution and 26% of
      species have been registered from only one continent. Data on AMF distribution
      challenge the "Everything is everywhere" hypothesis in favor of the "moderate
      endemicity model" for species distribution. Data from this study provide a
      foundation to formulate and test hypotheses of biogeographic patterns and
      processes in Glomeromycota.

PMID- 30187124
TI  - Forensic features for Yunnan Lisu ethnic minority and phylogenetic structure
      exploration among 26 Chinese populations.
AB  - The genetic polymorphisms of 15 autosomal short tandem repeat (STR) loci included
      in the AmpFlSTR(r)SinofilerTM kit were evaluated from 508 unrelated healthy
      individuals of the Lisu ethnic minority living in Chuxiong Yi Autonomous
      Prefecture, Yunnan province, southwest of China. Fourteen of the 15 loci reached
      the Hardy-Weinberg equilibrium after Bonferroni correction. These loci were
      examined to determine allele frequencies and forensic statistical parameters. The
      genetic relationship between the Lisu population and other Chinese populations
      were also estimated. The combined discrimination power and probability of
      excluding paternity of the 15 STR loci were 0.999 999 999 999 999 999 654 and
      0.999 998 882, respectively. These results suggest that the 15 STR loci are
      highly polymorphic, which is suitable for forensic personal identification and
      paternity testing.

PMID- 30187125
TI  - Abdominal pain, nausea, vomiting, and ascites in a 14-year-old girl with systemic
      lupus erythematosus: Questions.

PMID- 30187126
TI  - Abdominal pain, nausea, vomiting, and ascites in a 14-year-old girl with systemic
      lupus erythematosus: Answers.

PMID- 30187129
TI  - Choroidal thickness changes stratified by outcome in real-world treatment of
      diabetic macular edema.

PMID- 30187127
TI  - Energy expenditure associated with walking speed and angle of turn in children.
AB  - PURPOSE: Recent studies have suggested that turning is power intensive. Given the
      sporadic and irregular movement patterns of children, such findings have
      important implications for the assessment of true energy expenditure associated
      with habitual physical activity. The purpose of this study was to investigate the
      influence of walking speed and angle, and their interaction, on the energy
      expenditure of healthy children. METHODS: 20 children (10.1 +/- 0.5 years; 10
      boys) participated in the study. On two separate days, participants completed a
      turning protocol involving 3-min bouts of walking at one of the 16 speed (2.5,
      3.5, 4.5, and 5.5 km h- 1) and angle (0 degrees , 45 degrees , 90 degrees , and
      180 degrees ) combinations, interspersed by 3 min seated rest. The movement
      involved 5 m straight walking interspaced with prescribed turns with speed
      dictated by a digital, auditory metronome. Breath-by-breath gas exchange was
      measured, in addition to tri-axial acceleration and magnetic field intensity
      recorded at 100 Hz. RESULTS: Mixed models revealed a significant main effect for
      speed (p < 0.006) and angle (p < 0.006), with no significant interaction between
      speed and angle (p > 0.006). Significant differences to straight-line walking
      energy expenditure within speed were established for 3.5 and 5.5 km h- 1 for 180
      degrees  turns (~ 13% and ~ 30% increase, respectively). CONCLUSION: These
      findings highlight the importance of accounting for the magnitude and frequency
      of turns completed when estimating children's habitual physical activity and have
      significant implications for the assessment of daily energy expenditure.

PMID- 30187130
TI  - Greater Access to Long Acting Beta2 Agonists Is Associated with Less Hospital
      Admissions Due to COPD: A Longitudinal Nation-Wide Study.
AB  - PURPOSE: Long Acting Beta2 Agonists (LABA) prevent COPD exacerbations in strictly
      standardized clinical trials. Our aim was to evaluate the relationship between
      the amount of LABA provided by the government and the trend in COPD hospital
      admission (HA) rate in Brazil. METHODS: This is a longitudinal large-scale real
      life study. We calculated COPD HA rate and the number of subjects per 105
      inhabitant who received LABA supplied by the government in each Brazilian
      municipality, between years 2004 and 2013. We used Poisson Multilevel Regression
      analysis to calculate the rate ratio between LABA dispensation rate and COPD HA
      rate. RESULTS: In Brazil, COPD HA rate reduced 59% among subjects between 40 and
      59 years of age and 60% among subjects older than 59 years of age. Most of the
      5506 Brazilian municipalities reduced COPD HA rate [4149 (75%) municipalities &
      1357 (25%) municipalities]. The dispensation of LABA was greater among
      municipalities that reduced COPD HA rate. In the 40-59 age group, the gap in LABA
      dispensation between the two groups of municipalities increased during the study
      period from 90.40 to 614.28 subjects per 105 inhabitants. In the > 59 age group,
      the gap in LABA dispensation increased from 35.87 to 912.99 subjects per 105
      inhabitants. For each one hundred subjects who received LABA there was less one
      HA (RR 0.99, 95 CI 0.99-0.99). CONCLUSIONS: COPD HA rate reduced in Brazil. LABA
      dispensation growth was associated with COPD HA rate reduction.

PMID- 30187128
TI  - Pathological changes of the nasolacrimal duct in rabbit models of chronic
      dacryocystitis: correlation with lacrimal endoscopic findings.
AB  - PURPOSE: The aim of this study was to explore the pathological changes of the
      nasolacrimal duct in rabbits with experimentally induced obstructive
      dacryocystitis in correlation with lacrimal endoscopic findings. METHODS: The
      rabbit model of obstructive dacryocystitis was created by injecting 0.15 ml of
      self-curing resin into the lacrimal duct. The control group received 0.15 ml of
      normal saline. Within 16 weeks after the obstructive, lacrimal endoscopy and
      pathological examination of the nasolacrimal duct were conducted at different
      time points of 1, 2, 4, 8, and 16 weeks. RESULTS: In the control group, lacrimal
      endoscopy revealed pink and smooth mucosa; and the pathological analysis revealed
      an epithelial layer that was composed of superficial columnar cells and a deep
      basal epithelial layer. The experimental rabbits showed clinical manifestations
      of obstructive dacryocystitis a week after the injection of self-curing resin. At
      weeks 1 and 2, the lacrimal endoscopy showed mucosal hyperemia and hemorrhagic
      spots on the nasolacrimal duct; and the pathological features included epithelial
      cell swelling and inflammatory cell infiltration. At weeks 4 and 8, the
      experimental group showed alternatively red and white mucosa under the lacrimal
      endoscopy, and the pathological features included proliferative epithelium
      accompanied by papillary hyperplasia. At week 16, the experimental group showed
      pale and coarse mucosa and white membrane-like layer covering the mucosal
      surface, and the pathological features included epithelial necrosis, squamous
      metaplasia, and sub-epithelial fibrosis. CONCLUSION: The mucosa of the
      nasolacrimal duct showed different pathological features at different time points
      after lacrimal duct obstruction, which was well correlated with the endoscopic
      findings. It is possible to predict the pathological stages by the endoscopic
      observation in NLOD patients.

PMID- 30187131
TI  - Pneumothorax in Patients with Pulmonary Langerhans Cell Histiocytosis.
AB  - INTRODUCTION: Pneumothorax often develops in pulmonary Langerhans cell
      histiocytosis (PLCH), but some patients take a long time to be correctly
      diagnosed. OBJECTIVES: This study assessed the frequency of pneumothorax in PLCH
      and analysed the role of chest computed tomography (CT) in the prompt diagnosis.
      PATIENTS AND MATERIAL: Of the 90 patients with PLCH seen from 2000 to 2015, 29
      (32%) had pneumothorax as the initial finding. In this group, 18 (62%) patients
      were diagnosed within 1 month, whereas the diagnosis was delayed for 4-120 months
      in 11 (38%) patients. RESULTS: Patients who had pneumothorax as the initial sign
      of PLCH tended to be younger (mean age 27.7 +/- 7.92 vs. 39.9 +/- 13.21 years; P
      = 0.0001), male (69% vs. 43%; P = 0.028), smoked less (mean pack/years 8.4 +/-
      6.85 vs. 19 +/- 17.16; P = 0.003), and had a significantly lower mean FVC (77.96
      +/- 19.62 vs. 89.47 +/- 21.86% pred.; P = 0.015) and FEV1 (68.6 +/- 19.93 vs.
      79.4 +/- 21.48% pred.; P = 0.03 than patients who had no pneumothorax. Recurrent
      pneumothorax was diagnosed more frequently in the group with a delayed diagnosis
      (82% vs. 39%; P = 0.02). CT was performed in all of the patients who were
      diagnosed promptly, but in none of the patients with a delayed diagnosis.
      CONCLUSIONS: Patients who had pneumothorax as the initial sign of PLCH were
      younger, more frequently men, and had greater respiratory impairment than those
      who had no pneumothorax. CT in patients with pneumothorax led to a correct
      diagnosis of this disease.

PMID- 30187132
TI  - iPro70-FMWin: identifying Sigma70 promoters using multiple windowing and minimal
      features.
AB  - In bacterial DNA, there are specific sequences of nucleotides called promoters
      that can bind to the RNA polymerase. Sigma70 ([Formula: see text]) is one of the
      most important promoter sequences due to its presence in most of the DNA
      regulatory functions. In this paper, we identify the most effective and optimal
      sequence-based features for prediction of [Formula: see text] promoter sequences
      in a bacterial genome. We used both short-range and long-range DNA sequences in
      our proposed method. A very small number of effective features are selected from
      a large number of the extracted features using multi-window of different sizes
      within the DNA sequences. We call our prediction method iPro70-FMWin and made it
      freely accessible online via a web application established at
      http://ipro70.pythonanywhere.com/server for the sake of convenience of the
      researchers. We have tested our method using a standard benchmark dataset. In the
      experiments, iPro70-FMWin has achieved an area under the curve of the receiver
      operating characteristic and accuracy of 0.959 and 90.57%, respectively, which
      significantly outperforms the state-of-the-art predictors.

PMID- 30187133
TI  - Comparison of contrast-enhanced ultrasound targeted biopsy versus standard
      systematic biopsy for clinically significant prostate cancer detection: results
      of a prospective cohort study with 1024 patients.
AB  - PURPOSE: To assess contrast-enhanced ultrasound (CEUS) targeted biopsy (TB) for
      clinically significant prostate cancer (PCa) detection compared with systematic
      biopsy (SB). METHODS: A total of 1024 consecutive patients scheduled for prostate
      biopsy were enrolled in this prospective study. CEUS was performed by an
      experienced radiologist blinded to all clinical data. Suspicious lesions on
      postcontrast images were sampled in addition to standard 12-core SB. The
      clinically significant PCa detection rate by CEUS-TB was evaluated in comparison
      with SB in the total cohort and in different subgroups. RESULTS: In 378 of 1024
      patients (36.9%), the diagnosis of PCa was histologically confirmed. PCa was
      detected by CEUS-TB in 306 patients (29.9%, 306/1024) and SB in 317 patients
      (31.0%, 317/1024, P = 0.340). Among 378 PCa patients, 326 (86.2%, 326/378) were
      diagnosed with significant PCa using Epstein criteria. The significant PCa
      detection rate of CEUS-TB was 28.7% (294/1024), which was higher than that of SB
      (25.3%, 259/1024, P = 0.000). CEUS-TB resulted in 67 additional cases of
      clinically significant PCa, including 51 patients missed by SB and 16 patients
      under-graded by SB. Conversely, SB detected 32 additional significant PCa missed
      by TB. In the subgroup analysis, CEUS-TB yielded a higher significant cancer
      detection rate than SB in patients with a PSA level <= 10.0 ng/ml or prostate
      volume from 30 to 60 ml. CONCLUSION: The clinically significant PCa detection
      rate could be improved by the extra sampling of abnormalities on postcontrast
      images, especially in patients with a PSA level <= 10.0 ng/ml or prostate volume
      from 30 to 60 ml.

PMID- 30187134
TI  - Biomarkers in Islet Cell Transplantation for Type 1 Diabetes.
AB  - PURPOSE OF REVIEW: Islet transplantation, an important approach to achieve
      insulin independence for individuals with type 1 diabetes, is limited by the lack
      of accurate biomarkers to track beta-cell death post islet infusion. In this
      review, we will discuss existing and recently described biomarkers. RECENT
      FINDINGS: As beta cells are killed by the immune system, fragments of beta cell
      specific cell-free DNA and proteins are released into the periphery. Several
      different strategies to identify these fragments have been described. Some
      circulating, non-coding microRNAs, particularly miRNA-375 are also showing
      potential to reflect the rate of beta cell loss post-clinical islet
      transplantation. Recent advances in identifying accurate beta cell-specific
      biomarkers such as differentially methylated insulin cell-free DNA and
      circulating miRNA-375 may help predict clinical outcomes. More studies are
      required to examine the robustness of these biomarkers to detect chronic beta
      cell loss in islet transplantation recipients.

PMID- 30187135
TI  - Fluorometric determination of zinc(II) by using DNAzyme-modified magnetic
      microbeads.
AB  - A fluorometric assay for zinc ion is described that relies (a) on the use of an
      isothermal cycle to amplify the fluorescence signal, and (b) of magnetic beads
      (MBs) to completely remove unreacted DNA detection probes. Biotin and fluorophore
      labeled substrate (Zn-Sub) strands acting as detection probes were first
      assembled on MBs. Next, Zn(II)-specific DNAzyme (Zn-Enz) strands were hybridized
      with the Zn-Sub strands. In the presence of Zn(II), the Zn-Sub strands are
      cleaved. This results in the release of the shorter DNA fragments (containing
      fluorescent label) and in the dissociation of Zn-Enz strands. The dissociated Zn
      Enz strands then hybridize with the residual Zn-Sub strands and cleave them in a
      similar fashion. This leads to a target recycling amplification mechanism and in
      a cumulative signal amplification process. A strongly amplified signal is thus
      obtained in the presence of Zn(II). The use of MBs warrants that unreacted Zn-Sub
      strands can be magnetically separated from the solution. The method has a
      detection limit as low as 33 fM at a signal-to-noise ratio of 3 and a linear
      response in the 100 fM to 11 nM Zn(II) concentration range. It was applied to the
      determination of Zn(II) in spiked tap water and seawater samples, and the results
      compared well with data obtained by ICP-MS analysis. The method was also applied
      to the determination of Zn(II) in infant milk powder and breast milk. Graphical
      abstract Magnetic beads (MBs) carrying fluorescein-labeled substrate (Zn-Sub)
      strands were hybridized with Zn(II)-specific DNAzyme (Zn-Enz) and cleaved in the
      presence of Zn(II). After recycling, the unreacted Zn-Sub strands were removed
      with MBs and the released fluorescein tags are measured.

PMID- 30187136
TI  - Activation of angiotensin type 2 (AT2) receptors prevents myocardial hypertrophy
      in Zucker diabetic fatty rats.
AB  - AIMS: Compound 21 (C21), selective AT2 receptor agonist, has cardioprotective
      effects in experimental models of hypertension and myocardial infarction. The
      aims of the study was to evaluate the effect of C21, losartan, or both in Zucker
      diabetic fatty (ZDF) rats (type 2 diabetes) on (1) the prevention of myocardial
      hypertrophy; (2) myocardial expression of phosphatase and tensin homolog (PTEN),
      a target gene of miR-30a-3p, involved in myocardial remodelling. METHODS:
      Experiments were performed in ZDF (n = 33) and in control Lean (8) rats. From the
      6th to the 20th week of age, we administered C21 (0.3 mg/kg/day) to 8 ZDF rats. 8
      ZDF rats were treated with losartan (10 mg/kg/day), 8 rats underwent combination
      treatment, C21+ losartan, and 9 ZDF rats were left untreated. Blood glucose and
      blood pressure were measured every 4 weeks. At the end of the study the hearts
      were removed, the apex was cut for the quantification of PTEN mRNA and miR-30a-3p
      expression (realtime-PCR). Myocardial hypertrophy was evaluated by
      histomorphometric analysis, and nitrotyrosine expression (as marker of oxidative
      stress) by immunohistochemistry. RESULTS: ZDF rats had higher blood glucose (p <
      0.0001) with respect to control Lean rats, while blood pressure did not change.
      Both parameters were not modified by C21 treatment, while losartan and losartan +
      C21 reduced blood pressure in ZDF rats (p < 0.05). miR-30a-3p expression was
      increased in ZDF rats (p < 0.01) and PTEN mRNA expression was decreased (p <
      0.05). ZDF rats developed myocardial hypertrophy (p < 0.01) and increased
      oxidative stress (p < 0.01), both were prevented by C21 or losartan, or
      combination treatment. C21 or losartan normalized the expression of miR-30a-3p
      and PTEN. CONCLUSIONS: Activation of AT2 receptors or AT1 receptor blockade
      prevents the development of myocardial hypertrophy in ZDF rats. This occurs
      through the modulation of the miR-30a-3p/PTEN interaction.

PMID- 30187137
TI  - Evaluation of the water quality status of two surface water reservoirs in a
      Mediterranean island.
AB  - A 1-year monitoring study is presented on the chemical status of two surface
      water reservoirs in a decentralized Mediterranean island. Water samples were
      collected at varying depths in the two surface water reservoirs and different
      seasons between November 2015 and September 2016, covering both wet and dry
      periods of the year. Samples were analyzed in order to determine major chemical
      parameters and priority substances based on the EU Water Framework Directive
      (2000/60/EC) and the latest revision of the Priority Substances Policy Directive
      (2013/39/EU). Tested parameters in both reservoirs did not exceed the set limits.
      Increased pollutant concentrations were observed in the bottom samples. More than
      200 pesticide active substances were determined but none of them was above the
      parametric trigger value (0.1 MUg L-1). Toxic metals were not detected in the
      examined water samples, whereas the relatively high concentrations of Mn and Cu
      in the bottom samples are mainly attributed to geogenic background
      concentrations. Based on the results of the present study, it can be concluded
      that the chemical situation of both water reservoirs is considered acceptable;
      however, continuous monitoring should be implemented in the area.

PMID- 30187138
TI  - The adsorption of human defensin 5 on bacterial membranes: simulation studies.
AB  - Human alpha-defensin 5 (HD5) is one of the important antimicrobial peptides
      (AMPs) used against a broad-spectrum of pathogens, especially Gram-negative
      bacteria. HD5 kills by disrupting and making a pore in the bacterial membrane.
      The presence of lipopolysaccharide (LPS), located on a membrane surface, is found
      to have an impact on HD5's activity, where such binding mechanism in microscopic
      detail remains unclear. In this work, we therefore employed molecular dynamics
      (MD) simulations to investigate the binding mechanisms of HD5 on LPS in
      comparison to a bare DMPC lipid membrane. Two oligomers, dimer and tetramer, are
      studied here. Apparently, the membrane structure influences the protein binding
      affinity. HD5 binds tighter to a lipid membrane than LPS. Both dimeric and
      tetrameric HD5 can penetrate deeply into a phosphate layer in a lipid membrane,
      whereas only facial contacts are observed for LPS systems. The proteins appear to
      stay in the polar area instead of diving into a hydrophobic region. Furthermore,
      it happens in all cases that residues in the active region (A1, T2, R6, R13, R32)
      contribute to the membrane adsorption. The breakdown of tetramer into two dimers
      is also found. This implies that the dimer is more favorable for membrane
      binding. Moreover, both dimeric and tetrameric HD5 can significantly disrupt a
      LPS layer, whilst no serious distortion of lipid membrane is obtained. This
      emphasizes the importance of LPS on HD5 activity.

PMID- 30187139
TI  - Usability Testing of a Smartphone Application for Delivering Qigong Training.
AB  - A Qigong App was designed to promote a more flexible mode of delivering qigong
      training than face-to-face, with which individuals can access to this mind-body
      aerobic exercise more readily. The objective of the study was to examine the
      usability and acceptance of the App. Target participants were Cantonese- or
      Putonghua-speaking adults and owned a smartphone. First we conducted a pilot
      trial with 14 participants to examine the navigation feature of the App, followed
      by a main test. In the main test, another 100 participants reviewed the Qigong
      App and filled in a questionnaire on usability (System Usability Scale) and user
      acceptance (i.e., attitude, perceived ease of use, perceived usefulness,
      intention to use, and satisfaction), of which 89 completed the same questionnaire
      in a two-week interval. Qualitative feedback yielded from the pilot trial was
      summarized, and descriptive statistics, t-tests, and linear regressions were used
      in quantitative data analysis of the main test. The mean composite usability
      score in the main test was satisfactory (77.62 out of 100). Descriptive analyses
      showed that the majority of users found the Qigong App pleasant, user friendly,
      and useful for learning qigong. Participants indicated positive ratings for the
      items assessing usability and acceptance of the App. Regression results showed
      that certain characteristics predicted the ratings for some items, e.g., age as a
      predictor of scores of usability and perceived ease of use. The study provided
      researchers and practitioners with evidence of the usability and acceptance of an
      alternative qigong training mode that can enhance participants' access and
      motivation to practice qigong.

PMID- 30187140
TI  - Correction to: Bioreducible Poly(Amino Ethers) Based mTOR siRNA Delivery for Lung
      Cancer.
AB  - Under the heading "Methods-Synthesis of the Bioreducible Modified-PAE (mPAE)", on
      page 3, line 14-17, there is an error. The quantity unit of PAE and 2
      iminothiolane hydrochloride needs to be corrected to mg instead of g.

PMID- 30187141
TI  - Correction to: Sleep and physical activity: a cross-sectional objective profile
      of people with rheumatoid arthritis.
AB  - The original article can be found online.

PMID- 30187142
TI  - Colorimetric aptasensor for Campylobacter jejuni cells by exploiting the
      peroxidase like activity of Au@Pd nanoparticles.
AB  - The authors describe a method for colorimetric determination of Campylobacter
      jejuni (C. jejuni) in milk samples. It is based on the interaction of a specific
      DNA aptamer with surface protein in the cell membranes of C. jejuni. Specific
      binding of the aptamer with the cell membrane leads to an uptake of aptamer from
      solution. As a result, the concentration of aptamer floating in the solution is
      reduced. In the presence of large quantities of aptamer, the surface of added
      Au@Pd nanoparticles (NPs) is covered with aptamer via electrostatic interactions.
      Hence, they cannot act as a peroxidase mimic and oxidize the substrate 3,3',5,5'
      tetramethylbenzidine (TMB) to give a blue product. However, when the aptamer is
      bound by the target cells, the surface of the NPs is not blocked by aptamer and
      the NPs exert a strong peroxidase -like activity. Under defined experimental
      conditions, the intensity of the blue color increases with the concentration of
      C. jejuni, and as little as 100 CFU.mL-1 can bedetected in milk. Graphical
      abstract A colorimetric aptasensor for assay Campylobacter jejuni whole cell in
      food samples was investigated. This assay was designed based on interaction of
      specific DNA aptamer with surface protein in c. jejuni cell membrane without any
      modification of aptamer.

PMID- 30187144
TI  - Genomic and biological characterization of a new member of the genus Phikmvvirus
      infecting phytopathogenic Ralstonia bacteria.
AB  - Bacterial wilt caused by Ralstonia spp., soil-borne Gram-negative bacteria, is
      considered one of the most important plant diseases in tropical and subtropical
      regions of the world. A large number of bacteriophages capable of lysing or
      physiologically reprogramming cells of Ralstonia spp. have been reported in Asia.
      Despite the potential use of these organisms in the management of bacterial wilt,
      information on viruses that infect Ralstonia spp. is nonexistent in the Americas.
      We isolated a virus that infects Ralstonia spp. from a soil sample in the state
      of Minas Gerais, Brazil. Microscopy and genomic and phylogenetic analysis allowed
      us to classify the virus as a member of the family Podoviridae, genus
      Phikmvvirus. In spite of its relationship to Ralstonia virus RSB3, an Asian
      isolate, genomic and biological characteristics showed that the virus isolated in
      Brazil, tentatively named "Ralstonia virus phiAP1" (phiAP1), belongs to a new
      species. phiAP1 has EPS depolymerase activity and contains two putative virion
      associated peptidoglycan hydrolases (VAPGHs), which reveals a robust mechanism of
      pathogenesis. Furthermore, phiAP1 specifically infects Ralstonia solanacearum, R.
      pseudosolanacearum and R. syzygii, causing cell lysis, but it was not able to
      infect thirteen other bacteria that were tested. Together, these characteristics
      highlight the biotechnological potential of this virus for the management of
      bacterial wilt.

PMID- 30187143
TI  - Chimeric Newcastle disease virus-vectored vaccine protects chickens against H9N2
      avian influenza virus in the presence of pre-existing NDV immunity.
AB  - A chimeric Newcastle disease virus (NDV) vector (NDV/AI4-TFHN) was constructed
      with the replacement of the ectodomains of the fusion and hemagglutinin
      neuraminidase proteins by those from avian paramyxovirus type 2. The chimeric
      virus induced high antibody response in chickens pre-immunized with NDV. A
      recombinant vaccine candidate, NDV/AI4-TFHN-H9, expressing the hemagglutinin of
      H9N2 avian influenza virus, was generated, on the basis of the chimeric NDV
      vector mentioned above. The NDV/AI4-TFHN-H9 vaccine elicited H9-specific
      hemagglutination inhibition antibodies in chickens pre-immunized with NDV
      vaccine, and reduced the numbers of chickens shedding virus after H9N2 challenge.
      NDV/AI4-TFHN-H9 could serve as an alternative vaccine for the prevention of H9N2
      infection in commercial poultry flocks.

PMID- 30187146
TI  - Climate change mitigation in Canada's forest sector: a spatially explicit case
      study for two regions.
AB  - BACKGROUND: We determine the potential of forests and the forest sector to
      mitigate greenhouse gas (GHG) emissions by changes in management practices and
      wood use for two regions within Canada's managed forest from 2018 to 2050. Our
      modeling frameworks include the Carbon Budget Model of the Canadian Forest
      Sector, a framework for harvested wood products that estimates emissions based on
      product half-life decay times, and an account of marginal emission substitution
      benefits from the changes in use of wood products and bioenergy. Using a
      spatially explicit forest inventory with 16 ha pixels, we examine mitigation
      scenarios relating to forest management and wood use: increased harvesting
      efficiency; residue management for bioenergy; reduced harvest; reduced
      slashburning, and more longer-lived wood products. The primary reason for the
      spatially explicit approach at this coarse resolution was to estimate
      transportation distances associated with delivering harvest residues for heat
      and/or electricity production for local communities. RESULTS: Results
      demonstrated large differences among alternative scenarios, and from alternative
      assumptions about substitution benefits for fossil fuel-based energy and products
      which changed scenario rankings. Combining forest management activities with a
      wood-use scenario that generated more longer-lived products had the highest
      mitigation potential. CONCLUSIONS: The use of harvest residues to meet local
      energy demands in place of burning fossil fuels was found to be an effective
      scenario to reduce GHG emissions, along with scenarios that increased the
      utilization level for harvest, and increased the longevity of wood products.
      Substitution benefits from avoiding fossil fuels or emissions-intensive products
      were dependent on local circumstances for energy demand and fuel mix, and the
      assumed wood use for products. As projected future demand for biomass use in
      national GHG mitigation strategies could exceed sustainable biomass supply,
      analyses such as this can help identify biomass sources that achieve the greatest
      mitigation benefits.

PMID- 30187145
TI  - Functional outcomes and clinical strength assessment after infraspinatus-sparing
      surgical approach to scapular fracture: Does it really make a difference?
AB  - BACKGROUND: Surgical treatment of scapular fractures with posterior approach is
      frequently associated with postoperative infraspinatus hypotrophy and weakness.
      The aim of this retrospective study is to compare infraspinatus strength and
      functional outcomes in patients treated with the classic Judet versus modified
      Judet approach for scapular fracture. PATIENTS AND METHODS: 20 cases with
      scapular neck and body fracture treated with posterior approach for lateral
      border plate fixation were reviewed. In 11 of 20 cases, we used the modified
      Judet approach (MJ group), and in 9 cases we used the classic Judet approach (CJ
      group). All fractures were classified according to the AO classification system.
      At follow-up examinations, patients had X-ray assessment with acromiohumeral
      distance (AHD) measurement, clinical evaluation, active range of motion (ROM)
      examination, Constant Shoulder Score, and Disability of the Arm, Shoulder and
      Hand (DASH) Score. Infraspinatus strength assessment was measured using a
      dynamometer during infraspinatus strength test (IST) and infraspinatus scapular
      retraction test (ISRT). RESULTS: Demographic data did not significantly differ
      between the CJ group and MJ group, except for mean follow-up, which was 4.15
      years in the CJ group and 2.33 in the MJ group (p < 0.001). All X-ray
      examinations showed fracture healing. AHD was significantly decreased in the CJ
      group (p = 0.006). We did not find significant differences in active ROM between
      the MJ and CJ groups in the injured arm (p < 0.05). The Constant Score was 75.83
      (+/-14.03) in the CJ group and 82.75 (+/-10.72) in the MJ group (p = 0.31); DASH
      Score was 10.16 in the CJ group and 6.25 in the MJ group (p = 0.49). IST showed
      mean strength of 8.38 kg (+/-1.75) in the MJ group and 4.61 kg (+/-1.98) in the
      CJ group (p = 0.002), ISRT test was 8.7 (+/-1.64) in the MJ group and 4.95 (+/
      2.1) in the CJ group (p = 0.002). Infraspinatus hypotrophy was detected during
      inspection in six patients (five in the CJ group and one in the MJ group); it was
      related to infraspinatus strength weakness in IST and ISRT (p < 0.001).
      CONCLUSIONS: Infraspinatus-sparing surgical approach for scapular fracture avoids
      infraspinatus hypotrophy and external-rotation strength weakness. We suggest use
      of the modified Judet approach for scapular fracture and to restrict the classic
      Judet approach to only when the surgeon believes that the fracture is not easily
      reducible with a narrower exposure. LEVEL OF EVIDENCE: Level IV.

PMID- 30187147
TI  - Rectal cancer developing from an anastomotic site 18 years after resection due to
      intussusception caused by Peutz-Jeghers polyposis in a 31-year-old man: a case
      report.
AB  - BACKGROUND: Peutz-Jeghers syndrome (PJS) is an autosomal dominant disorder
      characterized by hamartomatous polyposis of the gastrointestinal tract. It is
      associated with a high risk of malignancy in the gastrointestinal tract, as well
      as in other organs. We report a case of colon cancer at the anastomotic site that
      occurred 18 years after high anterior resection of the rectum for intussusception
      caused by Peutz-Jeghers polyposis. CASE PRESENTATION: A 31-year-old man with PJS,
      who had undergone high anterior resection of the rectum for intussusception at
      the age of 12, presented to our hospital complaining of hematochezia. Colonoscopy
      revealed a hemorrhagic tumor protruding from the anastomotic site, which was
      histologically diagnosed as an adenocarcinoma. We performed a low anterior
      resection of the rectum including the anastomotic site, with combined resection
      of the strongly adherent ileum. Histological examination revealed that the
      adenocarcinoma had developed from the submucosal area, where the normal rectal
      mucosa had been incorporated into the stromal and bone tissues, resulting in
      heterotopic ossification in the anastomotic region. These findings suggested that
      the reconstructive surgical procedure or postoperative complications, such as
      anastomotic leakage, had formed the cavity where the cancer had developed.
      CONCLUSIONS: We concluded that the cancer might be derived from the rectal mucosa
      with malignant potential that was present in the anastomotic region and
      exacerbated by the presence of chronic inflammation in the cavity after the
      patient's initial operation.

PMID- 30187149
TI  - Abnormal aortic stiffness in patients with bicuspid aortic valve: phenotypic
      variation determined by magnetic resonance imaging.
AB  - The aim of this study was to assess aortic stiffness in patients with bicuspid
      aortic valve (BAV), and to determine if differences exist among the BAV
      phenotypes. Stiffness was measured by pulse wave velocity (PWV) determined using
      velocity-encoded magnetic resonance imaging (VENC-MRI). VENC-MRI was performed in
      100 BAV patients and 45 normal controls. PWV was determined between the mid
      ascending and mid descending aorta. The BAV phenotypes were characterized using
      steady-state free precession (SSFP) images acquired across the face of the aortic
      valve, and classified as follows: right-left cusp (R-L) fusion, right and non
      coronary cusp (R-NC) fusion, and left and non-coronary cusp (L-NC) fusion. The
      following BAV phenotypes were identified: 76 R-L, 23 R-NC, and 1 L-NC fusion. BAV
      patients demonstrated significantly greater PWV compared to normal controls,
      after adjusting for age (9.16 vs. 3.83 m/s; p < 0.0001). Furthermore, PWV was
      significantly greater in patients with R-NC fusion than those with R-L fusion
      phenotype (12.27 vs. 7.97 m/s; p < 0.001). There was significantly increased PWV
      from VENC-MRI in BAV patients compared to normal controls. Thisis the first to
      demonstrate the association of different BAV phenotypes and aortic stiffness.
      VENC-MRI PWV assessment potentially represents a novel parameter for enhanced
      surveillance and may alter surgical triage of aorta in this high risk group.

PMID- 30187148
TI  - Prophylactic aprepitant is better than salvage for carboplatin-based
      chemotherapy: a propensity score-matched analysis.
AB  - Aprepitant prevents chemotherapy-induced nausea and vomiting (CINV) in
      carboplatin-containing chemotherapy. However, it is unknown whether aprepitant
      salvage therapy after the development of emesis is as effective as adding
      prophylactic aprepitant to doublet therapy with dexamethasone and a 5-HT3
      receptor antagonist from the first cycle of chemotherapy. To compare the
      antiemetic efficacy of aprepitant between salvage and prophylactic administration
      in the second cycle of carboplatin-containing chemotherapy, twenty-two NSCLC
      patients who developed CINV in the first cycle of carboplatin-containing therapy
      without aprepitant (salvage group) and 44 patients who received aprepitant
      (prophylaxis group) were extracted from the pooled data of two clinical trials,
      with adjustment for age, sex, and chemotherapeutic regimen as co-variables using
      propensity score matching. In the second cycle of chemotherapy, both groups
      received aprepitant, and the rate of antiemetic complete response (no vomiting
      and no rescue therapy) at 5 days after chemotherapy was compared. The prophylaxis
      group demonstrated a significantly better overall complete response rate (88.6%;
      95% confidence interval [CI] 75.4-96.2) compared with that of observed for the
      salvage group (68.2%; 95% CI 45.1-86.1, p = 0.042). The prophylaxis group also
      demonstrated a significantly lower proportion of any-grade nausea (43.2%) and
      appetite loss (43.2%) than the salvage group (72.7%, p = 0.036 and 77.3%, p =
      0.010, respectively). Adding aprepitant to doublet therapy from the first cycle
      of carboplatin-containing chemotherapy may be more effective than salvage use of
      aprepitant after the development of CINV.

PMID- 30187150
TI  - Gender, Race, and Aggression in Mainstream Pornography.
AB  - The role of aggression in pornographic videos has been at the heart of many
      theoretical debates and empirical studies over the last four decades, with rates
      of reported aggression ranging widely. However, the interaction between gender
      and race in the production of aggressive pornographic contents remains
      understudied and undertheorized. We conducted a study of 172 popular free
      Internet pornographic videos, exploring gender and racial interactions and the
      depictions of men and women from various ethnic and racial groups in online
      pornography. Contrary to our theoretical expectations and to the findings of
      previous research, we found that videos featuring Black women were less likely to
      depict aggression than those featuring White women, while videos featuring Asian
      and Latina women were more likely to depict aggression. Our findings call for a
      reconceptualization of the role of race and ethnicity in pornography.

PMID- 30187151
TI  - Color Doppler ultrasonography is a reliable diagnostic tool in the diagnosis of
      extracranial vertebral artery dissections.
AB  - The purpose of this study was to evaluate the role of color Doppler sonography
      (CDS) in the diagnosis of extracranial vertebral artery dissections (EVADs). One
      hundred and fifty consecutive patients (age range 21-51 years, mean 44 years)
      with a clinical suspicion of vertebral artery dissection (VAD) were included in
      this study. All patients underwent CDS of vertebral arteries as the first-line
      imaging modality. Cervical T1-weighted fat-saturated axial MR images served as
      the gold standard. Of the 150 patients with a clinical suspicion of VAD, 27
      patients were ultimately diagnosed with EVADs based on fat-saturated T1-weighted
      MR imaging. MR imaging was considered positive when crescentic hyperintensity
      (methemoglobin signal) was demonstrated at the wall of the vertebral artery. CDS
      was positive in 21 of these 27 patients and revealed either intramural hematoma
      or a dissecting membrane with two lumina. The most frequent site of involvement
      was the V1 to proximal V2 segment. The sensitivity, specificity, and positive and
      negative predictive values of CDS in the diagnosis of EVADs were 77.8, 98.4,
      91.3, and 95.3%, respectively. CDS is a reliable diagnostic tool in the diagnosis
      of EVADs.

PMID- 30187152
TI  - Regional bedrock geochemistry associated with podoconiosis evaluated by
      multivariate analysis.
AB  - Podoconiosis is a disease whose etiology remains murky. Currently, the disease is
      attributed to particles that are believed to move through the skin and into the
      lymphatic system causing swelling of the lower legs. Identity of these particles
      or their composition remains unclear, though the presence of silicon and/or
      aluminum is often noted and frequently cited as causal agents. We applied
      multivariate analyses to the bedrock compositions of a large set of cases from an
      online database in an effort to identify underlying patterns or combinations of
      relative element abundances associated with podoconiosis-endemic regions. Using a
      combination of principal component analysis, discriminant function analysis, and
      ANOVA, we analyzed ten oxides from five regions on the African continent known to
      be associated with podoconiosis. The Hawaiian Islands were included as a control
      group since they are not known to have cases of podoconiosis despite similarity
      in geology and agricultural practices. Our analyses suggest that a unique
      alkaline- and silicon-rich geochemistry underlies regions associated with
      podoconiosis. Our results also imply that minerals enriched in incompatible
      elements, such as Ca, K, Mg, and Na, may be stronger predictors of the presence
      of the disease than either silicon or aluminum.

PMID- 30187154
TI  - Correction to: Fine mapping of powdery mildew resistance gene Pm4e in bread wheat
      (Triticum aestivum L.).
AB  - Unfortunately, the style of the units was incorrectly published ("cm" instead of
      "cM") throughout the original article.

PMID- 30187153
TI  - Individualized Dosing of Therapeutic Monoclonal Antibodies-a Changing Treatment
      Paradigm?
AB  - The introduction of monoclonal antibodies (mAbs) to the treatment of inflammatory
      bowel disease (IBD) was an important medical milestone. MAbs have been
      demonstrated as safe and efficacious treatments of IBD. However, a large
      percentage of patients either fail to respond initially or lose response to
      therapy after a period of treatment. Although there are factors associated with
      poor treatment outcomes in IBD, one cause for treatment failure may be low mAb
      exposure. Consequently, gastroenterologists have begun using therapeutic drug
      monitoring (TDM) to guide dose adjustment. However, while beneficial, TDM does
      not provide sufficient information to effectively adjust doses. The
      pharmacokinetics (PK) and pharmacodynamics (PD) of mAbs are complex, with
      numerous factors impacting on mAb PK and PD. The concept of dashboard-guided
      dosing based on Bayesian PK models allows physicians to combine TDM with factors
      influencing mAb PK to individualize therapy more effectively. One issue with TDM
      has been the slow turnaround of assay results, either necessitating an additional
      clinic visit for a sample or reacting to TDM results at a subsequent, rather than
      the current, dose. New point-of-care (POC) assays for mAbs are being developed
      that would potentially allow physicians to determine drug concentration quickly.
      However, work remains to understand how to determine what target exposure is
      needed for an individual patient, and whether the combination of POC assays and
      dashboards presents a safe approach with substantial outcome benefit over the
      current standard of care.

PMID- 30187155
TI  - Biosynthesis and function of terpenoid defense compounds in maize (Zea mays).
AB  - MAIN CONCLUSION: Maize produces an array of herbivore-induced terpene volatiles
      that attract parasitoids to infested plants and a suite of pathogen-induced non
      volatile terpenoids with antimicrobial activity to defend against pests. Plants
      rely on complex blends of constitutive and dynamically produced specialized
      metabolites to mediate beneficial ecological interactions and protect against
      biotic attack. One such class of metabolites are terpenoids, a large and
      structurally diverse class of molecules shown to play significant defensive and
      developmental roles in numerous plant species. Despite this, terpenoids have only
      recently been recognized as significant contributors to pest resistance in maize
      (Zea mays), a globally important agricultural crop. The current review details
      recent advances in our understanding of biochemical structures, pathways and
      functional roles of maize terpenoids. Dependent upon the lines examined, maize
      can harbor more than 30 terpene synthases, underlying the inherent diversity of
      maize terpene defense systems. Part of this defensive arsenal is the inducible
      production of volatile bouquets that include monoterpenes, homoterpenes and
      sesquiterpenes, which often function in indirect defense by enabling the
      attraction of parasitoids and predators. More recently discovered are a subset of
      sesquiterpene and diterpene hydrocarbon olefins modified by cytochrome P450s to
      produce non-volatile end-products such kauralexins, zealexins, dolabralexins and
      beta-costic acid. These non-volatile terpenoid phytoalexins often provide
      effective defense against both microbial and insect pests via direct
      antimicrobial and anti-feedant activity. The diversity and promiscuity of maize
      terpene synthases, coupled with a variety of secondary modifications, results in
      elaborate defensive layers whose identities, regulation and precise functions are
      continuing to be elucidated.

PMID- 30187157
TI  - Mucosal advancement flap for recurrent complex anal fistula: a repeatable
      procedure.
AB  - PURPOSE: Mucosal advancement flap (MAF) is the best option for complex anal
      fistula (AF) treatment. Recurrence is not rare and the best surgical option for
      his handling is a challenge considering the incontinence risk and the healing
      rate. We aimed to determine the feasibility and outcomes of a second MAF for
      recurrent complex AF previously treated with mucosal advancement flap. METHODS:
      We retrospectively identified 32 patients undergoing two or more MAF for
      recurrent AF in a larger cohort of 121 consecutive cases of MAF operated by the
      same senior colorectal surgeon. Only complex AF of cryptoglandular origin was
      enrolled. A long-term follow-up was performed collecting clinical and functional
      data. RESULTS: Among 121 patients (group A) treated with mucosal advancement
      flap, 32 (26.4%) (group B) recurred with a complex AF requiring a second mucosal
      advancement flap procedure. Success rate of group B is 78.1%. Six patients of
      group B recurred a second time, another MAF was performed with healing in all
      cases. Complication rate (Clavien Dindo 3b) of group B is 9.4% compared to 8.3%
      of group A. A slight continence deficit (Miller score 1, 2, and 4) was detected
      after the first MAF in 3 patients. The Miller score for these patients did not
      change after the subsequent MAF. CONCLUSIONS: MAF is effective for treatment of
      complex recurrent AF. A pre-existing MAF procedure does not worsen the healing
      rate of the second flap. The rate of surgical complications is similar with those
      reported in the literature for MAFs.

PMID- 30187156
TI  - Robotic versus laparoscopic intersphincteric resection for low rectal cancer: a
      systematic review and meta-analysis.
AB  - PURPOSE: Few studies have compared robotic and laparoscopic intersphincteric
      resection (ISR) in rectal cancer. Therefore, we performed a meta-analysis of
      recently published studies to compare perioperative outcomes of ISR for the
      treatment of low rectal cancer. METHODS: We performed a systematic literature
      search of the Ovid-Medline, Ovid-EMBASE, and Cochrane Central Register of
      Controlled Trials databases for studies comparing robotic and laparoscopic ISR in
      patients with low rectal cancer. Demographic and clinical data were extracted
      from articles that met the inclusion and exclusion criteria. Perioperative
      outcomes of interest included the rate of diverting stoma, open conversion rate,
      operation time, estimated blood loss, length of hospital stay, time to first
      flatus, and time to initiate the postoperative diet. Oncological outcomes
      included the number of retrieved lymph nodes, distal resection margin, proximal
      resection margin, circumferential resection margin, 3-year overall survival, 3
      year disease-free survival, and local recurrence. Postoperative complications
      included overall complications, a Dindo-Clavien classification >= III, and
      anastomotic leakage. All outcomes were compared between the two groups. RESULTS:
      We included 5 retrospective cohort studies with a total of 510 patients
      undergoing 273 (53.5%) robotic ISR procedures and 237 (46.5%) laparoscopic ISR
      procedures. The robotic ISR group lower conversion rate, lower blood loss, and
      longer operation times than the laparoscopic group. We also noted that fewer
      lymph nodes were harvested in the robotic ISR group; however, this difference was
      not statistically significant. Other outcomes were similar between the two
      groups. CONCLUSIONS: Robotic and laparoscopic ISR showed comparable perioperative
      outcomes, functional outcomes, and 3-year oncologic outcomes; however, robotic
      ISR was associated with a lower conversion rate and less blood loss despite
      longer operation times compared to laparoscopic ISR. These findings suggest that
      robotic ISR maybe a safe and effective technique for treating low rectal cancer
      in selected patients. The potential oncologic and functional benefits of robotic
      ISR should be evaluated in larger randomized controlled trials.

PMID- 30187158
TI  - Comparison of porcine collagen paste injection and rectal advancement flap for
      the treatment of complex cryptoglandular anal fistulas: a 2-year follow-up study.
AB  - BACKGROUND: Rectal advancement flap is the standard surgical treatment for
      complex cryptoglandular anal fistulas, while PermacolTM collagen paste is
      considered an innovative treatment option for anorectal fistulas. This study
      aimed to compare the clinical outcomes of patients with complex cryptoglandular
      fistulas treated by endorectal advancement flap versus PermacolTM paste. METHODS:
      This study was a retrospective analysis of patients with complex cryptoglandular
      anal fistulas. Thirty-one patients were treated with the rectal advancement flap
      (RAF group), while 21 were treated with PermacolTM paste injection (PP group). In
      PP group, the approach consisted of loose seton positioning followed several
      weeks later by closure internal opening with a resorbable sutures associated with
      paste injection into the fistula track. Clinical outcomes were assessed in terms
      of healing rate, faecal continence and patient satisfaction. RESULTS: Seton
      drainage was done in all patients in both groups for a median duration of 8 weeks
      (range 4-18 weeks) before the final surgery (p = 0.719). No patient had faecal
      incontinence (CGS >= 5) preoperatively. Five patients (16%) in the RAF group and
      one (5%) in the PP group experienced faecal incontinence postoperatively. The 2
      year disease-free survival was 65% in the RAF group and 52% in the PP group (p =
      0.659). The median satisfaction scores were 5 (range 1-10) in the RAF group and 7
      (range 2-10) in the PP group (p = 0.299). CONCLUSION: The RAF appeared superior
      to PP in terms of fistula healing, although this result was not statistically
      significant. On the contrary, PP has a potential advantage in terms of continence
      disorders. PermacolTM paste can be considered as the initial treatment option for
      complex cryptoglandular anal fistulas in patients with faecal continence
      disorders.

PMID- 30187160
TI  - Affinities of human NMDA receptor autoantibodies: implications for disease
      mechanisms and clinical diagnostics.
AB  - Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a common autoimmune
      encephalitis presenting with psychosis, dyskinesias, autonomic dysfunction and
      seizures. The underlying autoantibodies against the NR1 subunit are directly
      pathogenic by disrupting synaptic NMDAR currents. However, antibody titers
      correlate only partially with the clinical outcome, suggesting the relevance of
      other factors such as antibody affinity. We thus determined the binding curves of
      human monoclonal autoantibodies and patients' cerebrospinal fluid (CSF) against
      NR1-expressing HEK293 cells using flow cytometry. Antibody affinity was highly
      variable with binding constants (half-maximal concentration, c50) ranging from 1
      to 74 ug/ml for monoclonal antibodies. Comparing values of individual monoclonal
      antibodies with human CSF samples suggested that the CSF signal is predominantly
      represented by higher-affinity antibodies, potentially in a concentration range
      of NR1 antibodies between 0.1 and 5 ug/ml, roughly reflecting 1-10% of total CSF
      IgG in NMDAR encephalitis. Binding curves further depended on the CSF composition
      which must be considered when interpreting established clinical routine assays.
      Normalization of measurements using reference samples allowed high
      reproducibility. Accurate and reproducible measurement of NR1 antibody binding
      suggested that biophysical properties of the antibody might contribute to disease
      severity. Normalization of the data can be an elegant way to allow comparable
      inter-laboratory quantification of CSF NR1 antibody titers in autoimmune
      encephalitis patients, a prerequisite for use as surrogate markers in clinical
      trials. Based on our calculations, low-affinity antibodies can easily remain
      undetected in routine cell-based assays, indicating that their relation to
      clinical symptoms should be analyzed in future studies.

PMID- 30187161
TI  - Vascular vertigo: updates.
AB  - Discriminating strokes in patients with acute dizziness/vertigo is challenging
      especially when other symptoms and signs of central nervous involvements are not
      evident. Despite the developments in imaging technology over the decades, a
      significant proportion of acute strokes may escape detection on imaging
      especially during the acute phase or when the lesions are small. Thus, small
      strokes causing isolated dizziness/vertigo would have a higher chance of
      misdiagnosis in the emergency department. Even though several diagnostic
      algorithms have been advanced for acute vascular vertigo, we still await more
      comprehensive and sophisticated ones that can also be applied to transient
      vestibular symptoms due to vascular compromise. In this respect, vascular and
      perfusion imaging would be informative. Application of artificial intelligence
      and tele-consultation may be future perspectives for real-time decision in acute
      dizziness and vertigo. Several new constellations of ocular motor and vestibular
      findings have been added to the strokes involving the brainstem and cerebellum.
      Defining these characteristics would help understanding the function of central
      vestibular structures and allow more accurate localization of the strokes
      involving these structures.

PMID- 30187159
TI  - Targeting phosphocreatine metabolism in relapsing-remitting multiple sclerosis:
      evaluation with brain MRI, 1H and 31P MRS, and clinical and cognitive testing.
AB  - BACKGROUND/OBJECTIVES: Fluoxetine and prucalopride might change phosphocreatine
      (PCr) levels via the cAMP-PKA pathway, an interesting target in the
      neurodegenerative mechanisms of MS. METHODS: We conducted a two-center double
      blind, placebo-controlled, randomized trial including 48 relapsing-remitting MS
      patients. Patients were randomized to receive placebo (n = 13), fluoxetine (n =
      15), or prucalopride (n = 14) for 6 weeks. Proton (1H) and phosphorus (31P)
      magnetic resonance spectroscopy (MRS) as well as volumetric and perfusion MR
      imaging were performed at weeks 0, 2, and 6. Clinical and cognitive testing were
      evaluated at weeks 0 and 6. RESULTS: No significant changes were observed for
      both 31P and 1H MRS indices. We found a significant effect on white matter volume
      and a trend towards an increase in grey matter and whole brain volume in the
      fluoxetine group at week 2; however, these effects were not sustained at week 6
      for white matter and whole brain volume. Fluoxetine and prucalopride showed a
      positive effect on 9-HPT, depression, and fatigue scores. CONCLUSION: Both
      fluoxetine and prucalopride had a symptomatic effect on upper limb function,
      fatigue, and depression, but this should be interpreted with caution. No effect
      of treatment was found on 31P and 1H MRS parameters, suggesting that these
      molecules do not influence the PCr metabolism.

PMID- 30187164
TI  - Genetic landscape of isolated pediatric cataracts: extreme heterogeneity and
      variable inheritance patterns within genes.
AB  - Pediatric cataract represents an important cause of pediatric visual impairment.
      While both genetic and environmental causes for pediatric cataract are known, a
      large proportion remains idiopathic. The purpose of this review is to discuss
      genes involved in isolated pediatric cataract, with a focus on variable
      inheritance patterns within genes. Mutations in over 52 genes are known to cause
      isolated pediatric cataract, with a major contribution from genes encoding for
      crystallins, transcription factors, membrane proteins, and cytoskeletal proteins.
      Interestingly, both dominant and recessive inheritance patterns have been
      reported for mutations in 13 different cataract genes. For some genes, dominant
      and recessive alleles represent distinct types of mutations, but for many,
      especially missense variants, there are no clear patterns to distinguish between
      dominant and recessive alleles. Further research into the functional effects of
      these mutations, as well as additional data on the frequency of the identified
      variants, is needed to clarify variant pathogenicity. Exome sequencing continues
      to be successful in identifying novel genes associated with congenital cataract
      but is hindered by the extreme genetic heterogeneity of this condition. The large
      number of idiopathic cases suggests that more genes and potentially novel
      mechanisms of gene disruption remain to be identified.

PMID- 30187163
TI  - Non-coding RNAs in retinal development and function.
AB  - Accumulating evidence on the role of non-protein-coding RNA sequences in the
      regulation of gene expression is greatly expanding our understanding of the flow
      of genetic information within biological systems. The interplay between protein
      coding and non-coding RNAs (ncRNAs) is essential for tissue development,
      homeostasis, and function. NcRNAs can be divided in short ncRNAs, whose main
      subtype is represented by microRNAs, and long ncRNAs, which constitute a more
      heterogeneous class. The retina is a light-sensitive tissue consisting of highly
      interconnected cell types and is the primary target of many genetic diseases.
      Among these, the genetically heterogeneous group of inherited retinal diseases
      (IRDs) represents the most frequent monogenic cause of visual impairment that can
      ultimately lead to blindness. Here, we provide an overview on the role of ncRNAs
      in retinal development and function with an emphasis on microRNAs and on
      different types of long ncRNAs. We also review how sequence variations in ncRNAs
      can play a pathogenic role in IRDs as well as in multifactorial ocular disorders.
      These data indicate that a comprehensive study of the contribution of ncRNAs to
      the mutation repertoire associated with retinal disease can shed light on
      previously unknown pathophysiological mechanisms and open new therapeutic
      avenues. We conclude that a more comprehensive dissection of the pathogenic role
      of non-coding RNAs in retinal function and disease will not only improve our
      diagnostic ability, but will allow the development of novel targeted therapies
      for ocular disease.

PMID- 30187166
TI  - Novel KHDRBS1-NTRK3 rearrangement in a congenital pediatric CD34-positive skin
      tumor: a case report.
AB  - Cutaneous spindle-cell neoplasms in adults as well as children represent a
      frequent dilemma for pathologists. Along this neoplasm spectrum, the differential
      diagnosis with CD34-positive proliferations can be challenging, particularly
      concerning neoplasms of fibrohistiocytic and fibroblastic lineages. In children,
      cutaneous and superficial soft-tissue neoplasms with CD34-positive spindle cells
      are associated with benign to intermediate malignancy potential and include
      lipofibromatosis, plaque-like CD34-positive dermal fibroma, fibroblastic
      connective tissue nevus, and congenital dermatofibrosarcoma protuberans.
      Molecular biology has been valuable in showing dermatofibrosarcoma protuberans
      and infantile fibrosarcoma that are characterized by COL1A1-PDGFB and ETV6-NTRK3
      rearrangements respectively. We report a case of congenital CD34-positive
      dermohypodermal spindle-cell neoplasm occurring in a female infant and harboring
      a novel KHDRBS1-NTRK3 fusion. This tumor could belong to a new subgroup of
      pediatric cutaneous spindle-cell neoplasms, be an atypical presentation of a
      plaque-like CD34-positive dermal fibroma, of a fibroblastic connective tissue
      nevus, or represent a dermatofibrosarcoma protuberans with an alternative gene
      rearrangement.

PMID- 30187162
TI  - Significance of CSF NfL and tau in ALS.
AB  - Cerebrospinal fluid (CSF) neurofilament light chain (NfL) has emerged as putative
      diagnostic biomarker in amyotrophic lateral sclerosis (ALS), but it remains a
      matter of debate, whether CSF total tau (ttau), tau phosphorylated at threonine
      181 (ptau) and the ptau/ttau ratio could serve as diagnostic biomarker in ALS as
      well. Moreover, the relationship between CSF NfL and tau measures to further
      axonal and (neuro)degeneration markers still needs to be elucidated. Our analysis
      included 89 ALS patients [median (range) age 63 (33-83) years, 61% male, disease
      duration 10 (0.2-190) months] and 33 age- and sex-matched disease controls [60
      (32-76), 49%]. NfL was higher and the ptau/ttau ratio was lower in ALS compared
      to controls [8343 (1795-35,945) pg/ml vs. 1193 (612-2616), H(1) = 70.8, p <
      0.001; mean (SD) 0.17 (0.04) vs. 0.2 (0.03), F(1) = 14.3, p < 0.001], as well as
      in upper motor neuron dominant (UMND, n = 10) compared to classic (n = 46) or
      lower motor neuron dominant ALS [n = 31; for NfL: 16,076 (7447-35,945) vs. 8205
      (2651-35,138) vs. 8057 (1795-34,951)], Z >= 2.5, p <= 0.01; for the ptau/ttau
      ratio: [0.13 (0.04) vs. 0.17 (0.04) vs. 0.18 (0.03), p <= 0.02]. In ALS, NfL and
      the ptau/ttau ratio were related to corticospinal tract (CST) fractional
      anisotropy (FA) and radial diffusivity (ROI-based approach and whole-brain
      voxelwise analysis). Factor analysis of mixed data revealed a co-variance pattern
      between NfL (factor load - 0.6), the ptau/ttau ratio (0.7), CST FA (0.8) and UMND
      ALS phenotype (- 2.8). NfL did not relate to any further neuroaxonal injury
      marker (brain volumes, precentral gyrus thickness, peripheral motor amplitudes,
      sonographic cross-sectional nerve area), but a lower ptau/ttau ratio was
      associated with whole-brain gray matter atrophy and widespread white matter
      integrity loss. Higher NfL baseline levels were associated with greater UMN
      disease burden, more rapid disease progression, a twofold to threefold greater
      hazard of death and shorter survival times. The findings that higher CSF NfL
      levels and a reduced ptau/ttau ratio are more associated with clinical UMN
      involvement and with reduced CST FA offer strong converging evidence that both
      are markers of central motor degeneration. Furthermore, NfL is a marker of poor
      prognosis, while a low ptau/ttau ratio indicates extramotor pathology in ALS.

PMID- 30187167
TI  - Differentiated vulvar intraepithelial neoplasia (dVIN): the most helpful
      histological features and the utility of cytokeratins 13 and 17.
AB  - Differentiated vulvar intraepithelial neoplasia (dVIN) is the precursor lesion of
      HPV-negative vulvar squamous cell carcinoma (VSCC). The histopathological
      diagnosis of dVIN can be challenging, as it often resembles vulvar non-neoplastic
      epithelial disorders (NNED), especially lichen sclerosus (LS). We aimed to
      establish the most specific and reproducible histological features of dVIN and
      assessed cytokeratin 13 (CK13) and cytokeratin 17 (CK17) immunohistochemistry as
      a diagnostic aid. Consecutive cases of dVIN (n = 180) and LS (n = 105) from the
      period 2010 to 2013 were reviewed using a checklist of histological features.
      Each feature was recorded as 'present' or 'absent' and statistical comparison
      (dVIN vs LS) was made. Interobserver agreement between two pairs of pathologists
      was assessed for a subset of cases of dVIN (n = 31) and LS and other NNED (n =
      23). Immunohistochemistry with CK13, CK17, MIB1 and p53 was performed on dVIN,
      LS, and other NNED cases. Macronucleoli, features of disturbed maturation and
      angulated nuclei were significantly more common in dVIN than LS (p < 0.001). We
      found 'substantial agreement' for the diagnosis of dVIN (kappa = 0.71).
      Macronucleoli and deep keratinisation had the highest agreement. In dVIN, the
      mean percentage of cells staining with CK13 was 15 and with CK17, this was 74.
      For LS, the mean percentage of cells staining with CK13 was 31, and with CK17,
      this was 41. By plotting receiver operating characteristic curves (ROC), an area
      under the curve (AUC) of 0.52 was obtained for CK13, and an AUC of 0.87 was
      obtained for CK17. The most helpful histological features for diagnosing dVIN
      were macronucleoli, features of disturbed maturation, and angulated nuclei.
      Increased CK17 expression may have promise for supporting dVIN diagnosis.

PMID- 30187168
TI  - Surgical options for male breast cancer.
AB  - BACKGROUND: Male breast cancer (MBC) is a rare disease for which no randomised
      controlled trials (RCT) have been conducted to determine optimal surgical
      management. The available data have been reviewed to identify reasonable options
      and reveal areas in need of investigation. METHODS: All published series on the
      surgical management of MBC have been reviewed to determine approaches to
      treatment of the primary, the breast and the axilla together with the
      psychological sequelae of surgery. FINDINGS: Mastectomy is still the major
      surgical offer but a convincing case can be made for the use of neoadjuvant
      endocrine treatment in order to facilitate breast conserving surgery. Sentinel
      node biopsy has been successfully used for staging MBC although nomograms for
      prediction of nodal status are inadequately calibrated. There are psychological
      sequelae of mastectomy in males and as yet no evidence that the needs of those
      with MBC are being met. CONCLUSIONS: Collaborative studies are required so that
      men can participate in meaningful RCTs to provide an evidence-based rational
      foundation for the surgery of MBC.

PMID- 30187169
TI  - A new species of Hamaticolax (Copepoda: Bomolochidae) from Helicolenus
      dactylopterus (Delaroche, 1809) (Scorpaeniformes: Sebastidae) in NW Mediterranean
      deep waters and notes on patterns of host use and host-specificity of the genus.
AB  - Hamaticolax juanji n. sp. is described from specimens collected from the
      blackbelly rosefish Helicolenus dactylopterus Delaroche 1809 (Scorpaeniformes:
      Sebastidae). It is the second Hamaticolax species described and reported from the
      Mediterranean Sea, after Ha. resupinus Perez-i-Garcia, Carrasson and Boxshall,
      2017. It is distinguished from Ha. resupinus by the presence of only one dorsal
      naked seta on the third segment of the antennule (vs. four), two unequal short
      naked setae in distal part of the antenna (vs. four), and the absence of a minute
      spine on the third endopodal segment of leg 1, among others. It is differentiated
      from Ha. prolixus Cressey 1969 by a comparatively reduced fourth pedigerous
      somite, the presence of two naked setae on the third segment of the antennule
      (vs. three), two naked setae and three curved claws in the distal part of the
      apical segment of the antenna (vs. three and four), an outer naked seta on the
      basis of leg 2, and by larger length/width ratio of the third endopodal segment,
      among others. Hamaticolax juanji n. sp. also has relatively longer inner setae on
      the first and second endopodal segments of leg 4 than the two former species.
      Patterns of host-use and host-specificity of the genus Hamaticolax are also
      discussed. The frequently observed low host-specificity of its members may be
      better explained by host ecological similarity and host availability phenomena,
      rather than by host phylogenetic distance.

PMID- 30187171
TI  - Phylogenetic relationships within Dicrocoeliidae (Platyhelminthes: Digenea) from
      birds from the Czech Republic using partial 28S rDNA sequences.
AB  - Partial (D1-D3) 28S rRNA gene sequences from 16 isolates of digenean parasites of
      the family Dicrocoeliidae recovered from 16 bird species from the Czech Republic
      were used for phylogenetic reconstruction. Comparison with sequences available
      from GenBank suggests that the genus Brachylecithum is paraphyletic, requiring
      further validation and possible systematic revision. Although partial 28S rDNA is
      relatively conserved, analyses suggest that the following taxa are synonymous:
      Lutztrema attenuatum = L. monenteron = L. microstomum, Brachylecithum lobatum =
      B. glareoli. Zonorchis petiolatus is reassigned back to the genus Lyperosomum
      with L. collurionis as a junior synonym. The study revealed how complicated the
      systematics of the family Dicrocoeliidae is currently. The morphology of the
      group is variable, and the current distinguishing characters at species and even
      generic level are not sufficiently distinctive; it is difficult to identify the
      specimens correctly and identification of GenBank isolates is not reliable.
      Extensive sampling of isolates for both molecular and morphological studies is
      necessary to resolve the relationships within the family.

PMID- 30187170
TI  - First molecular detection of Theileria luwenshuni from goats in Myanmar.
AB  - Tick-borne intracellular protozoan parasites of the Theileria genus infect a wide
      range of both domestic and wild animals. In the present study, we describe the
      first PCR detection of Theileria luwenshuni in the blood of goats in Myanmar.
      Nested PCR targeting the Theileria 18S rRNA gene resulted in seven positive goats
      in central and northern Myanmar. Nucleotide sequencing of the PCR products
      revealed that all seven sequences were identical and showed 100% identity with T.
      luwenshuni sequences in GenBank from goats and sheep in China. Since T.
      luwenshuni parasites have recently been discovered and shown to have nationwide
      distribution in China, they might have been introduced into Myanmar via
      transboundary movement of infected domestic small ruminants and/or wild animals
      from China.

PMID- 30187174
TI  - [Medical Device Regulation as current challenge for the legally safe introduction
      of new technologies].
AB  - The main goal of the Medical Device Regulation (MDR) is the improvement of
      patient safety by laying down rules concerning the approval of medical devices
      for human use in the European Union. The MDR contains an extension of the
      conformity assessment procedure for products in the higher risk categories IIb
      and III. The clinical testing and assessment are regulated more strictly by e.g.
      the scrutiny process conducted by expert panels following the technical
      certification. The demand for documentation is vastly increasing due to more
      detailed registration (UDI) and an extension of post-market surveillance. The
      German Society of Surgery (DGCH) and the German Society for Biomedical
      Engineering have already defined a staged concept for innovation testing and
      clinical assessment during finalization of the MDR that contains the highest
      level of patient safety while simultaneously maintaining the potential for
      innovation. Essential elements are present in the MDR and can be implemented in a
      targeted way. The 3-year phase of national MDR-implementation must be used for a
      proactive adaptation. The DGCH is represented in the advisory council of the
      Federal Ministry of Health (BMG) by the Association of the Scientific Medical
      Societies in Germany (AWMF). The aim is a responsible harmonization of national
      structures with the regulations of the MDR by the construction of specific
      registries which should be the responsibility of medical societies. The early
      integration of health technology assessment will be of importance during the
      planning phase of product development to facilitate a positive decision on
      reimbursement.

PMID- 30187173
TI  - Melanocortin 2 receptor antagonists in canine pituitary-dependent
      hypercortisolism: in vitro studies.
AB  - Canine hypercortisolism is most often caused by an ACTH-secreting pituitary
      adenoma (pituitary-dependent hypercortisolism; PDH). An interesting target for a
      selective medical treatment of PDH would be the receptor for ACTH: the
      melanocortin 2 receptor (MC2R). In this study we investigated whether two peptide
      compounds, BIM-22776 (#776) and BIM-22A299 (#299), are effective MC2R antagonists
      in vitro. Their effects on cortisol production and mRNA expression of
      steroidogenic enzymes, MC2R and melanocortin 2 receptor accessory protein (MRAP)
      were evaluated in primary adrenocortical cell cultures (n = 8) of normal canine
      adrenal glands. Cortisol production stimulated by 50 nM ACTH was dose-dependently
      inhibited by #299 (inhibition 90.7 +/- 2.3% at 5 MUM) and by #776 (inhibition
      38.0 +/- 5.2% at 5 MUM). The ACTH-stimulated mRNA expression of steroidogenic
      enzymes, MC2R and MRAP was significantly inhibited by both compounds, but most
      potently by #299. These results indicate that canine primary cell culture is a
      valuable in vitro system to test MC2R antagonists, and that these compounds, but
      especially #299, are effective MC2R antagonists in vitro. To determine its
      efficacy in vivo, further studies are warranted. Antagonism of the MC2R is a
      promising potential treatment approach in canine PDH.

PMID- 30187172
TI  - Imaging Techniques in the Diagnosis and Management of Ocular Tumors: Prospects
      and Challenges.
AB  - Different types of imaging modalities are used in the diagnosis of ocular cancer.
      Selection of an imaging modality is based on the features of a tumor as well as
      the inherent characteristics of the imaging technique. It is vital to select an
      appropriate imaging modality in diagnosis of ocular tumor with confidence. This
      review focuses on five most commonly used imaging modalities, i.e., positron
      emission tomography-computed tomography (PET/CT), single photon emission computed
      tomography (SPECT), optical coherence tomography (OCT), ultrasound (US), and
      magnetic resonance imaging (MRI). The principal of imaging modalities is briefly
      explained, along with their role in the diagnosis and management of the most
      common ocular tumors such as retinoblastoma and uveal melanoma. Further, the
      diagnostic features of ocular tumors corresponding to each imaging modality and
      possibilities of utilizing imaging techniques in the process of ocular drug
      development are included in this review.

PMID- 30187175
TI  - BRAF V600E mutant papillary craniopharyngiomas: a single-institutional case
      series.
AB  - PURPOSE: To describe the clinical, radiographic and surgical outcomes in a cohort
      of patients with BRAF V600E mutant papillary craniopharyngiomas. METHODS: A
      retrospective review was performed to identify all patients with a histological
      diagnosis of CP operated upon at a single institution between 2005 and 2017. All
      cases with adequate material were sequenced to confirm the presence of BRAF V600E
      mutation. RESULTS: Sixteen patients were included in the present study. Approach
      was endoscopic endonasal (EEA) in 14 and transcranial (TCA) in 2. All patients
      were adult with an average age of 50 years (24-88). Radiographic review
      demonstrated that the majority (93.7%) were suprasellar and twelve (75%) had
      third ventricular involvement. No tumor showed evidence of calcifications and
      68.7% were mixed solid-cystic. All patients had some evidence of hypopituitarism
      and 62.5% had hypothalamic disturbances. GTR was achieved in 11/14 (78.6%) EEA
      and 0/2 (0%) TCA (p < 0.05). The mean length of stay was 17.5 days in the TCA
      group and 7.6 days in the EEA group (p < 0.05). There were no CSF leaks. Post
      operatively, eleven (68.7%) developed new DI or new hypopituitarism. Nine
      increased their BMI with a mean increase of 12.3%, whereas six patients lost
      weight with a mean decrease of 5.3%. CONCLUSIONS: BRAF V600E mutant papillary
      tumors represent a clearly distinct clinical-pathological entity of
      craniopharyngiomas. These are generally non-calcified suprasellar tumors that
      occur in adults. These distinct characteristics may someday lead to upfront
      chemotherapy. When surgery is necessary, EEA may be preferred over TCA.

PMID- 30187178
TI  - Safety and efficacy of cryoballoon ablation for the treatment of atrial
      fibrillation in elderly patients.
AB  - BACKGROUND: Catheter ablation (CA) is an established therapy for treatment of
      atrial fibrillation (AF). However, data about AF ablation using the cryoballoon
      (CB) in the elderly population are sparse. The aim of this single center
      retrospective study is to evaluate the safety and efficacy of CB ablation in
      patients >= 75 years compared to patients < 75 years. METHODS AND RESULTS: Fifty
      five consecutive patients aged >= 75 years (elderly group) were compared with 183
      patients aged < 75 years (control group). All patients underwent pulmonary vein
      isolation (PVI) using the second-generation CB. The mean age in the elderly group
      was 78 +/- 2.8 years and 60.8 +/- 9.5 in the control group (p < 0.001). During
      11.8 +/- 5.4 months of follow-up, single procedure success rate for the elderly
      and the control group was 72.8 and 76%, respectively (p = 0.37). During redo
      ablation (n = 40), low-voltage areas in the LA were more frequently observed in
      elderly patients compared to the control group [1.0 (IQR 0-2.0) segments vs 2.0
      (IQR 2.0-3.0) segments, respectively, p = 0.03]. The most common complication was
      transient phrenic nerve palsy, which only occurred in patients < 75 years (0 vs
      7, p = 0.33). No severe complication such as procedure-related deaths, atrio
      esophageal fistula, or cerebrovascular embolic events occurred. CONCLUSIONS: Our
      data strengthen the value of CB ablation for the treatment of AF as an effective
      and safe procedure in elderly patients, with similar success and complication
      rates when compared with a younger population.

PMID- 30187179
TI  - Coronary CT angiography (CCTA) using third-generation dual-source CT for ruling
      out in-stent restenosis.
AB  - AIMS: Late in-stent restenosis (ISR) has become increasingly important, in
      particular due to neo-atherosclerosis. CCTA is a highly sensitive method for
      detecting coronary plaques. Its diagnostic accuracy regarding ISR is
      controversial. Stent artifacts can impede image quality, but recent developments
      in CT-technology may help to overcome some of these problems and allow for
      improved diagnostic accuracy. METHODS: Consecutive patients after previous
      coronary revascularization who had stable symptoms or signs of possible disease
      progression were examined using a third-generation dual-source CT scanner. After
      the scan, patients were followed for clinical events (MACE) over a mean of 399
      days. Patients with high-grade stenoses were referred for invasive coronary
      angiography (ICA), unclear findings were further evaluated either by ICA or
      functional testing. RESULTS: Overall, 226 patients were included. A total of 457
      stents were evaluated (2.0 +/- 1.4 per patient). Mean stent diameter was 2.9 +/-
      0.45 mm. In 61%, a high-pitch protocol was employed. Mean dose-length product
      (DLP) of CCTA was 159.2 mGy cm, corresponding to 2.2 mSv using a conversion
      factor of k = 0.014. Mean amount of contrast agent was 58.3 +/- 12.5 ml. In 145
      patients (64%), CCTA was negative. In this group, one MACE occurred (acute
      coronary syndrome) during follow-up in a patient who had also undergone
      unremarkable ICA. In 23 patients (10%), CCTA detected 28 ISR which were confirmed
      and treated by ICA (true positive). In 27 patients (12%), ISR was suspected by
      CCTA but excluded by ICA (false positive), 30 patients (13%) had unclear findings
      and normal non-invasive tests. No MACE occurred during follow-up in these
      patients. One patient was misclassified in CCTA as having intermediate and not
      high-grade ISR who underwent revascularization within 3 months. Eleven patients
      (5%) were lost to follow-up. During follow-up, eight patients had myocardial
      infarctions due to five ISRs and three de novo lesions. No patient died. In cases
      with unclear or false-positive findings, the amount of stents was significantly
      higher, stents were smaller and patients had a higher BMI. CONCLUSION: In almost
      two-thirds of symptomatic patients with previous coronary stent implantation, ISR
      could be ruled out by CCTA. 10% of patients had definite ISR. The rate of false
      negative findings was low (< 1%), whereas the rate of false positive or
      inconclusive findings was 25%, leading to invasive rule-out of ISR by ICA in 12%.
      CCTA appears valuable as a tool for safely excluding ISR. It might help to avoid
      invasive diagnostic procedures. Further analyses are warranted, in particular
      regarding the influence of stent dimensions and the total amount of stents in a
      patient.

PMID- 30187177
TI  - Co-culture of rat luteal cells with islet cells enhances islet viability and
      revascularization.
AB  - Islet cell transplantation is a major treatment strategy for type I diabetes, and
      has proven to be effective for maintaining glucose homeostasis. However, this
      treatment requires an extended period of immunosuppression to prevent rejection
      and recurrent transplantation to maintain function. Thus, to enhance the
      properties of transplanted islet cells, we examined the effect of the co-culture
      of luteal cells, which secrete progesterone, on islet cell viability,
      functionality, and revascularization. It was found that islet viability and
      functionality were higher in the co-cultured group than in single cultures of
      islets at 48 and 96 h, in parallel with increased progesterone and vascular
      endothelial growth factor (VEGF) secretion from luteal cells. In the co-culture
      groups, VEGF levels at 48 and 96 h and CD31 levels at 48 h were significantly
      higher than those in the islet groups (p < 0.001 and p < 0.05, respectively), and
      basic fibroblast growth factor (bFGF) levels were increased at 96 h (p < 0.001).
      Thus, co-culture with luteal cells may increase islet vascularity by enhancing
      VEGF and bFGF levels for up to 96 h, which could help to markedly increase the
      pre-transplantation time to allow for effective immunosuppression therapy. This
      method may also promote islet cell viability and functionality. Progesterone and
      angiogenic factors secreted from luteal cells may be responsible for these
      positive effects.

PMID- 30187176
TI  - Diabetes Treatment in the Elderly: Incorporating Geriatrics, Technology, and
      Functional Medicine.
AB  - PURPOSE OF REVIEW: The current approach to diabetes in the elderly incorporates
      components from the comprehensive geriatric approach. The most updated guidelines
      from the American Diabetes Association reflect influence from the consensus made
      in 2012 with the American Geriatrics Society. Notably, the framework included the
      evaluation for geriatric syndromes (falls and urinary incontinence), functional
      and cognitive abilities. The goal for this review is to provide an updated
      summary of treatment strategies for community-dwelling older adults. We
      identified the need to expand our approach by addressing innovative approaches
      and scientific concepts from telemedicine, functional medicine, and geriatrics.
      RECENT FINDINGS: Findings on cardiovascular protection with sodium-glucose co
      transporter 2 inhibitors (SGLT-2i) and some glucagon-like peptide 1 receptor
      agonists (GLP-1RA) support their use for older patients with diabetes. However,
      careful consideration for agent selection must incorporate the presence of
      geriatric issues, such as geriatric syndromes, or functional and cognitive
      decline, as they could increase the risk and impact adverse reactions.
      Telemedicine interventions can improve communication and connection between older
      patients and their providers, and improve glycemic control. Functional medicine
      concepts can offer additional adjuvant strategies to support the therapeutic
      interventions and management of diabetes in the elderly. A systematic review
      confirmed the efficacy and safety of metformin as first-line therapy of type 2
      diabetes in the older adult, but multiple reports highlighted the risk for
      vitamin B12 deficiency. Randomized controlled trials showed the efficacy and
      safety of antihyperglycemic agents in the elderly, including some with longer
      duration and lesser risk for hypoglycemia. Randomized clinical trials showed
      cardiovascular protection with SGLT-2i (empagliflozin, canagliflozin) and GLP-1RA
      (liraglutide, semaglutide). The most current guidelines recommend addressing for
      geriatric syndromes, physical and cognitive function in the elderly, in order to
      individualize targets and therapeutic strategies. Clinicians managing diabetes in
      the elderly can play a major role for the early detection and evaluation of
      geriatric issues in their patients. Telemedicine interventions improve glycemic
      control, and certain functional medicine strategies could be adjuvant
      interventions to reduce inflammation and stress, but more studies focused on the
      elderly population are needed.

PMID- 30187182
TI  - Treatment of pediatric multilevel cervical spine fractures in resource-limited
      settings: a case report.
AB  - AIM OF THE STUDY: The main purpose of this study was to highlight the therapeutic
      approach of pediatric multilevel noncontiguous cervical spine fractures in
      resource-limited settings. CASE PRESENTATION: We report the case of a 15-year-old
      teenager with C1, C2, C4, C6, and C7 fractures following fall from height treated
      with a modified external fixator. At final follow-up, he fully recovered
      neurologic functions with bone healing. CONCLUSION: The modified external fixator
      is a therapeutic modality for pediatric multilevel noncontiguous cervical spine
      fractures.

PMID- 30187181
TI  - Endoscopic treatment of intraventricular ependymal cysts in children: personal
      experience and review of literature.
AB  - OBJECT: Intracranial ependymal cysts are rare neuroepithelial cysts that occur
      less frequently than arachnoid cysts. The cysts are most often intraparenchymal,
      but they are rarely reported to be intraventricular. This study evaluates the
      role of endoscopy in the treatment of intraventricular ependymal cysts (IVECs).
      METHODS: Twelve pediatric patients (mean age 4.3 years) with symptomatic IVECs
      were the subject of this study. The cyst was located inside the lateral ventricle
      in all cases (100%), it was present in trigone (10 patients, 83.3%), and in
      temporal horn (2 patients, 16.7%). Concomitant hydrocephalus was present in two
      patients (16.7%). All patients underwent operations through a purely endoscopic
      procedure. Communication of the cyst with the subarachnoid space was performed in
      six patients (50%); endoscopic cystocisternostomy was performed in four patients
      (33.3%), and endoscopic cystoventriculostomy in two patients (16.7%). RESULTS:
      Postoperative clinical improvement associated with postoperative reduction in
      cyst size was encountered in ten patients (83.3%). Improvement of hydrocephalus
      occurred in both patients who had hydrocephalus (100%). There were no deaths or
      permanent morbidity. Among the follow-up period (mean 44.3 months), none of the
      patients required a repeat endoscopic procedure due to recurrence of symptoms or
      increase in cyst size. CONCLUSION: Intraventricular ependymal cysts can be
      effectively treated by endoscopy. Endoscopic fenestration of the cyst wall into
      subarachnoid space, basal cisterns, or ventricular system can be used in the
      treatment of these patients with postoperative symptomatic improvement and
      reduction of cyst size. The procedure is simple, effective, minimally invasive,
      and associated with low morbidity and mortality rates.

PMID- 30187180
TI  - EGb761 improves the cognitive function of elderly db/db-/- diabetic mice by
      regulating the beclin-1 and NF-kappaB signaling pathways.
AB  - To assess whether EGb761 could protect elderly diabetic mice with cognitive
      disorders and explore the role of beclin-1-mediated autophagy in these protective
      effects. Two-month-old male db/db-/- mice and wild-type C57/BL6 mice were
      randomly divided into six groups: db/db-/- control, db/db-/- 50 mg, db/db-/- 100
      mg, wild-type (WT) control, WT 50 mg, and WT 100 mg. EGb761 (50 mg/kg or 100
      mg/kg of bodyweight) was given by gavage once a day for 1 month from the age of 6
      months. Y-maze and social choice tests were performed at 8th months. The blood
      pressure was measured. The imaging changes in the brain were measured using
      magnetic resonance imaging (MRI). The expression and distribution of beclin-1,
      LC3, and NF-kappaB were detected using immunohistochemistry staining and western
      blotting. Ultrastructure alterations in the hippocampus were observed using
      transmission electron microscopy. Compared with WT mice, the learning ability,
      memory and overall cognitive function of db/db-/- mice decreased (P < 0.05), and
      EGb761 could significantly improve the learning and memory function of db/db-/-
      mice (P < 0.05). EGb761 significantly improved systolic blood pressure in db/db-/
      mice (P < 0.01). In addition, fMRI-bold showed a decline in the hippocampus of
      mice in the db/db-/- group compared with WT. EGb761 could improve these above
      changes. Immunohistochemistry staining and western blotting confirmed that EGb761
      significantly increased beclin-1 and reduced LC3-II/I levels in the brains of
      db/db-/- mice (P < 0.05). NF-kappaB levels were obviously higher in the db/db-/-
      group than that in the WT group, and EGb761 significantly reduced NF-kappaB
      levels in db/db-/- mice (P < 0.05). There was a trend of increased autophagosomes
      in db/db-/- mice, but EGb761 did not change obviously the number of
      autophagosomes. Compared with normal aged WT mice, aging db/db-/- mice had more
      common complications of cerebral small vessel disease and cognitive dysfunction.
      EGb761 could significantly improve the cognitive function of aging db/db-/- mice
      via a mechanism that may involve the regulation of beclin-1, LC3, and NF-kappaB.

PMID- 30187184
TI  - A case of transient thalamic dysphasia-considering the role of the thalamus in
      language.

PMID- 30187183
TI  - Fracture related ulnar and sciatic nerve transections: a report of two cases and
      literature review.
AB  - INTRODUCTION: Case reports, case series, and case control studies have looked at
      the incidence of complete nerve transection in the setting of fracture and the
      need for surgical exploration dating back to the 1920s. We present two cases of
      nerve laceration accompanying traumatic fracture with a thorough review of the
      literature. METHODS: We used the following search terms: "ulnar nerve" OR
      "sciatic nerve" AND "laceration" OR "transection" AND "fracture." Results were
      reviewed and included for discussion if they specifically reported ulnar or
      sciatic nerve laceration accompanying traumatic fracture. RESULTS: Our search
      yielded 15 papers reporting a total of 10 ulnar nerve lacerations and nine
      sciatic nerve lacerations. We present two additional cases. The first is a
      patient with a humerus fracture and complete ulnar nerve transection. The second
      case is a patient who suffered a femur fracture and complete transection of the
      sciatic nerve. CONCLUSION: Nerve laceration accompanying traumatic fracture is
      rare. We review the reported cases of nerve laceration and present two cases
      treated at our institution. Though uncommon, nerve laceration should be
      considered in the setting of traumatic fracture with neurological injury,
      particularly open fractures.

PMID- 30187185
TI  - Correction to: The sbGnRH-GTH system in the female short mackerel, Rastrelliger
      brachysoma (Bleeker, 1851), during breeding season: implications for low gamete
      production in captive broodstock.
AB  - The published online version of this article contained outdated Figs. 4 and 5.
      The original article has been corrected.

PMID- 30187186
TI  - A novel combination of quick response code and microfluidic paper-based
      analytical devices for rapid and quantitative detection.
AB  - Nowadays, there is great interest in the use of microfluidic paper-based
      analytical devices (MUPADs) for low-cost diagnostics. In most cases, the test
      equipment is needed. Here we report a new type of device-independent detection
      method based on timer-paper-based analytical devices, which can be tested by
      smartphone, and its application for cholesterol detection. The Quick Response
      code was designed as the timer component of this device. Wax printing method was
      employed to print the pattern on filter paper. The color and enzyme reagents have
      been immobilized in the hydrophilic channel to complete the colorimetric
      detection for cholesterol. Under laminar flow conditions of the cellulose
      network, the liquid volume of detection zone has been quantified by monitoring
      the fluid residence time on different area of the timer-paper-based devices. The
      precise monitoring of detection time can promote the accuracy of colorimetric
      detection. This is very important for the quantitative detection of paper-based
      analytical devices. One significant outcome of this report is that simple and
      accurate timer can be used for detection process self-clocking. The factors of
      total detection time have been investigated. The linear range of the calibration
      curve was 3.0 ~ 6.0 mmol L-1, with correlation coefficient of 0.9956. With the
      characteristic of easy to use, low cost and accurate monitoring of detection
      time, this kind of timer-paper-based devices can be applied to cholesterol or
      other substances rapid detection.

PMID- 30187187
TI  - Comparative study of aeropollen and pollinosis cases.
AB  - Research linking pollen grains in the air with allergy cases (pollinosis) is
      still incipient in Africa. To close this gap, aerosamplers were placed in
      Gbagada, Lagos State and harvested monthly from January 2013 to December 2014.
      Data obtained was correlated with allergy cases (wheezing cough, rhinitis, and
      allergic conjunctivitis) from Gbagada General Hospital Lagos. Dominant pollen
      grains recovered were those of Alchornea cordifolia, Amaranthaceae, Casuarina
      equisetifolia, Cyperaceae, and Poaceae. Pollinosis data revealed that wheezing
      cough had the highest records in 2013 (1153) and 2014 (1409) while individuals of
      the age group 15-49 years had the highest number of pollinosis cases for both
      years. Peak pollen season in 2013 was from October-December; similarly, October,
      November, and December recorded the highest incidence of wheezing cough (225),
      rhinitis (21), and allergic conjunctivitis (56) respectively. In 2014, peak
      pollen season was from October-March while October recorded the highest number of
      cases of allergic conjunctivitis and rhinitis (81 and 32 respectively) and
      wheezing cough cases were highest in November (299). Total pollen count had
      positive significant correlation (p <= 0.05) with wheezing cough cases for both
      years. Individually, each dominant pollen had positive significant correlation (p
      <= 0.05) with wheezing cough cases in 2013 while only Cyperaceae and Poaceae
      pollen had positive significant correlation (p <= 0.05) with wheezing cough in
      2014. Continuous collection of aeropollen and pollinosis data from more locations
      within Nigeria is recommended to provide an appropriate epidemiology of
      pollinosis cases in the country and ascertain possible responsible pollen grains.

PMID- 30187189
TI  - Theoretical study of the fragmentation of ionized benzophenone.
AB  - A detailed theoretical study of the various possible fragmentation reactions of
      the benzophenone radical cation was carried out for the first time. In the first
      step, we optimized the geometries of all the structures resulting from the
      fragmentation of this cation using density functional theory (DFT). Our
      calculations were performed in the gas phase using the aug-cc-pVTZ basis set and
      the PBE1PBE functional. We determined the optimized structural parameters and the
      harmonic and anharmonic frequencies. The energies corresponding to all the
      optimized molecules were recalculated using the coupled cluster method CCSD(T).
      Upon comparing the fragmentation reaction energies, we found that the principal
      reaction was that leading to C7H5O+ and .C6H5. We were able to theoretically
      demonstrate the existence of different fragments of the benzophenone cation: CO,
      CO+., .C6H5, C6H5+, .C7H5O, C7H5O+, biphenyl, and (biphenyl)+., and we found that
      the main products of the fragmentation reactions of the benzophenone cation are
      C7H5O+ and (biphenyl)+., which have been observed experimentally using slow
      photoelectron spectroscopy (SPES). Our theoretical results are in good agreement
      with the experimental results from benzophenone cation spectroscopy and
      fragmentation obtained using Benoit Soep's equipment at Synchrotron SOLEIL.

PMID- 30187190
TI  - Impact of re-excision of residual adjacent vulvar intraepithelial neoplasia (VIN
      III) and histological tumour-free margin (hTFM) on survival in primary squamous
      cell carcinoma of vulva.
AB  - BACKGROUND: hTFM in primary vulvar cancer is an important prognostic factor.
      Ideally, a diameter of > 8 mm should be achieved after primary surgery. The role
      of VIN III persistence after primary surgery in vulvar cancer is still unclear.
      The main objective of the current study was to study the role of residual VIN III
      re-excision and compare differences in disease-free survival among patients with
      different hTFM and in primary vulvar cancer. METHODS: Forty-two patients with
      residual adjacent VIN III after primary surgery for vulvar cancer which were
      operated between 2000 and 2016 in our clinic were enrolled in this retrospective
      study. Re-excision rates for residual adjacent VIN III were calculated. According
      to the histological margin patients were divided into three group: < 3, 3-8 and >
      8 mm. Univariate and multivariate analyses were conducted using the Kaplan-Meier
      method and Cox proportional hazards models, respectively. RESULTS: The vast
      majority of patients had pT1b stage (57.1%), grading G2 (71.4%) and lymph node
      negative (45.3%) disease at first diagnosis. The re-excision rate was 57.1%. The
      5-year disease-free survival (DFS) rates in patients with < 3, 3-8 and > 8 mm
      hTFM were 50.0, 50.0 and 81.0%, respectively (p = 0.032). The 5-year DFS rates in
      patients with re-excision and without re-excision for VIN III were 77.3 and
      52.9%, respectively (p = 0.060). In univariate analysis was solely hTFM > 8 mm a
      prognostic factor for DFS (p = 0.017). CONCLUSIONS: hTFM may be a potential
      prognostic indicator for DFS in vulvar cancer patients. Re-excision for residual
      adjacent VIN III could not be established as a prognostic factor for DFS after
      primary surgery in squamous cell cancer of vulva.

PMID- 30187188
TI  - Co-Delivery of Teriflunomide and Methotrexate from Hydroxyapatite Nanoparticles
      for the Treatment of Rheumatoid Arthritis: In Vitro Characterization,
      Pharmacodynamic and Biochemical Investigations.
AB  - PURPOSE: The present investigation was aimed at developing Teriflunomide (TEF)
      and Methotrexate (MTX) loaded hydroxyapatite nanoparticles and increasing
      tolerability towards combination therapy against rheumatoid arthritis by reducing
      hepatotoxicity. METHODS: Drug-loaded HAp-NPs were synthesized by wet-chemical
      precipitation method and optimized by Box-Behnken experimental design. The
      developed NPs were subjected to in vitro and in vivo characterization. In-vivo
      pharmacodynamics and biochemical studies were performed on adjuvant- induced
      arthritis model treated with different formulations; MTX-TEF-SOL, TEF-HAp-NP, MTX
      HAp-NP, TEF-MTX-HAp-NP, FOLITRAX-10 and AUBAGIO. RESULTS: The size of the
      optimized formulations, TEF-HAp-NP and MTX-HAp-NP, was found to be 224.3 +/-
      83.80 nm and 268.3 +/- 73.86 nm with drug loading 53.11 +/- 0.84% and 67.04 +/-
      1.12% respectively. In vitro release of TEF from TEF-HAp-NP (70.41 +/- 1.22%) and
      MTX from MTX-HAp-NP (82.43 +/- 1.31%) up to 24 h revealed sustained release
      pattern. Results of the arthritic assessment study showed a significant (P <
      0.05) reduction in ankle diameter (61.30 +/- 7.42) and arthritis score (2.35 +/-
      0.24) with a marked restoration of ankle joint micro-architecture in TEF-MTX-HAp
      NP treated group. During Hepatotoxicity studies, liver histopathology revealed
      that the formulation MTX-TEF-HAp-NP was least hepatotoxic with less hepatocyte
      swelling and fibrous connective tissue proliferation while Folitrax-10 was found
      to be most hepatotoxic. Biochemical studies revealed that Folitrax-10
      significantly (P < 0.05) increased the GOT (313.64 +/- 16) and GPT level (334.46
      +/- 13) while insignificant (P > 0.05) change in GOT (263.68 +/- 17) and GPT
      (229.38 +/- 10) level was recorded with TEF-MTX-HAp-NP. CONCLUSIONS: We report
      that the subcutaneous delivery of TEF-MTX-HAp-NP was most effective as it
      successfully reduced the dosage by half for maximizing therapeutic efficacy and
      minimizing side effects. Graphical Abstract ?.

PMID- 30187192
TI  - Cytoarchitecture, probability maps, and functions of the human supplementary and
      pre-supplementary motor areas.
AB  - The dorsal  mesial frontal cortex contains the supplementary motor area (SMA) and
      the pre-supplementary motor area (pre-SMA), which play an important role in
      action and cognition. Evidence from cytoarchitectonic, stimulation, and
      functional studies suggests structural and functional divergence between the two
      subregions. However, a microstructural map of these areas obtained in a
      representative sample of brains in a stereotaxic reference space is still
      lacking. In the present study we show that the dorsal mesial frontal motor cortex
      comprises two microstructurally different brain regions: area SMA and area pre
      SMA. Area-specific cytoarchitectonic patterns were studied in serial histological
      sections stained for cell bodies of ten human postmortem brains. Borders of the
      two cortical areas were identified using image analysis and statistical features.
      The 3D reconstructed areas were transferred to a common reference space, and
      probabilistic maps were calculated by superimposing the individual maps. A
      coordinate-based meta-analysis of functional imaging data was subsequently
      performed using the two probabilistic maps as microstructurally defined seed
      regions. It revealed that areas SMA and pre-SMA were strongly co-activated with
      areas in precentral, supramarginal and superior frontal gyri, Rolandic operculum,
      thalamus, putamen and cerebellum. Both areas were related to motor functions, but
      area pre-SMA was involved in more complex processes such as learning, cognitive
      processes and perception. The here described subsequent analyses led to
      converging evidence supporting the microstructural, and functional segregation of
      areas SMA and pre-SMA, and maps will be made available to the scientific
      community to further elucidate the microstructural substrates of motor and
      cognitive control.

PMID- 30187193
TI  - A characterization of laminar architecture in mouse primary auditory cortex.
AB  - Laminar architecture of primary auditory cortex (A1) has long been investigated
      by traditional histochemical techniques such as Nissl staining, retrograde and
      anterograde tracings. Uncertainty still remains, however, about laminar
      boundaries in mice. Here we investigated the cortical lamina structure by
      combining neuronal tracing and immunofluorochemistry for laminar specific
      markers. Most retrogradely labeled corticothalamic neurons expressed Forkhead box
      protein P2 (Foxp2) and distributed within the laminar band of Foxp2-expressing
      cells, identifying layer 6. Cut-like homeobox 1 (Cux1) expression in layer 2-4
      neurons divided the upper layers into low expression layers 2/3 and high
      expression layers 3/4, which overlapped with the dense terminals of vesicular
      glutamate transporter 2 (vGluT2) and anterogradely labeled lemniscal
      thalamocortical axons. In layer 5, between Cux1-expressing layers 2-4 and Foxp2
      defined layer 6, retrogradely labeled corticocollicular projection neurons mostly
      expressed COUP-TF interacting protein 2 (Ctip2). Ctip2-expressing neurons formed
      a laminar band in the middle of layer 5 distant from layer 6, creating a laminar
      gap between the two laminas. This gap contained a high population of commissural
      neurons projecting to contralateral A1 compared to other layers and received
      vGluT2-immunopositive, presumptive thalamocortical axon collateral inputs. Our
      study shows that layer 5 is much wider than layer 6, and layer 5 can be divided
      into at least three sublayers. The thalamorecipient layers 3/4 may be separated
      from layers 2/3 using Cux1 and can be also divided into layer 4 and layer 3 based
      on the neuronal soma size. These data provide a new insight for the laminar
      structure of mouse A1.

PMID- 30187191
TI  - A framework based on sulcal constraints to align preterm, infant and adult human
      brain images acquired in vivo and post mortem.
AB  - Robust spatial alignment of post mortem data and in vivo MRI acquisitions from
      different ages, especially from the early developmental stages, into standard
      spaces is still a bottleneck hampering easy comparison with the mainstream
      neuroimaging results. In this paper, we test a landmark-based spatial
      normalization strategy as a framework for the seamless integration of any
      macroscopic dataset in the context of the Human Brain Project (HBP). This
      strategy stems from an approach called DISCO embedding sulcal constraints in a
      registration framework used to initialize DARTEL, the widely used spatial
      normalization approach proposed in the SPM software. We show that this strategy
      is efficient with a heterogeneous dataset including challenging data as preterm
      newborns, infants, post mortem histological data and a synthetic atlas computed
      from averaging the ICBM database, as well as more commonly studied data acquired
      in vivo in adults. We then describe some perspectives for a research program
      aiming at improving folding pattern matching for atlas inference in the context
      of the future HBP's portal.

PMID- 30187194
TI  - Foxp2 loss of function increases striatal direct pathway inhibition via increased
      GABA release.
AB  - Heterozygous mutations of the Forkhead-box protein 2 (FOXP2) gene in humans cause
      childhood apraxia of speech. Loss of Foxp2 in mice is known to affect striatal
      development and impair motor skills. However, it is unknown if striatal
      excitatory/inhibitory balance is affected during development and if the imbalance
      persists into adulthood. We investigated the effect of reduced Foxp2 expression,
      via a loss-of-function mutation, on striatal medium spiny neurons (MSNs). Our
      data show that heterozygous loss of Foxp2 decreases excitatory (AMPA receptor
      mediated) and increases inhibitory (GABA receptor-mediated) currents in D1
      dopamine receptor positive MSNs of juvenile and adult mice. Furthermore, reduced
      Foxp2 expression increases GAD67 expression, leading to both increased
      presynaptic content and release of GABA. Finally, pharmacological blockade of
      inhibitory activity in vivo partially rescues motor skill learning deficits in
      heterozygous Foxp2 mice. Our results suggest a novel role for Foxp2 in the
      regulation of striatal direct pathway activity through managing inhibitory drive.

PMID- 30187195
TI  - Corneal hysteresis and glaucoma.
AB  - PURPOSE: To review and summarize the characteristics of corneal hysteresis (CH)
      and its relationship with glaucoma. METHODS: A PubMed search was carried out
      using the terms "corneal hysteresis", "glaucoma", and "biomechanics". Up to March
      2018, all studies published in English are included in this review. RESULTS: The
      value of CH reflects the ability of corneal tissue to absorb and release energy
      during bidirectional flattening. It is an important biomechanical parameter of
      the cornea. The CH value of healthy adults is about 11 mmHg. The measurement of
      CH is reproducible and different. People have different CH values, which are
      determined by the shape of the individual's cornea. The study found that all
      types of glaucoma, including primary open angle glaucoma, angle-closure glaucoma,
      normal tension glaucoma, congenital glaucoma, binocular asymmetrical glaucoma, CH
      values are lower than normal people, therefore, CH is therefore a good indicator
      of glaucoma diagnosis and screening. Lower CH values are associated with thinner
      retinal nerve fiber layer (RNFL), larger linear cup/disk ratio (LCDR) and degree
      of optic disc defect. A lower CH value can also result in a lower visual field
      index. CH and the basic intraocular pressure play a synergistic role in the
      progression of glaucoma. The study found that CH can change with changes in basic
      intraocular pressure, means CH increases when intraocular pressure decreases,
      while the CH decreases conversely when intraocular pressure increases. Most
      clinical case studies have shown a decrease in CH after LASER refractive surgery.
      CH has its limitations, such as corneal damage or corneal surgery, but in
      general, CH is a risk factor for glaucoma progression. CONCLUSION: CH is used as
      a predictor of glaucoma risk and may help to assess the effect of corneal
      thickness on intraocular pressure. The clinical significance of CH in the
      diagnosis and efficacy of glaucoma will become more explicit. In the future, CH
      can also play an important role in the diagnosis and treatment of glaucoma.

PMID- 30187196
TI  - More valid and reliable thrombophilia testing is required for predicting the
      recurrence and the required duration of treatment for venous thromboembolism.

PMID- 30187198
TI  - Artificial palpation in robotic surgery using haptic feedback.
AB  - BACKGROUND: The loss of tactile feedback in minimally invasive robotic surgery
      remains a major challenge to the expanding field. With visual cue compensation
      alone, tissue characterization via palpation proves to be immensely difficult.
      This work evaluates a bimodal vibrotactile system as a means of conveying applied
      forces to simulate haptic feedback in two sets of studies simulating an
      artificial palpation task using the da Vinci surgical robot. METHODS: Subjects in
      the first study were tasked with localizing an embedded vessel in a soft tissue
      phantom using a single-sensor unit. In the second study, subjects localized tumor
      like structures using a three-sensor array. In both sets of studies, subjects
      completed the task under three trial conditions: no feedback, normal force
      tactile feedback, and hybrid vibrotactile feedback. Recordings of correct
      localization, incorrect localization, and time-to-completion were used to
      evaluate performance outcomes. RESULTS: With the addition of vibrotactile and
      pneumatic feedback, significant improvements in the percentage of correct
      localization attempts were detected (p = 0.0001 and p = 0.0459, respectively)
      during the first experiment with phantom vessels. Similarly, significant
      improvements in correct localization were found with the addition of vibrotactile
      (p = 2.57E-5) and pneumatic significance (p = 8.54E-5) were observed in the
      second experiment involving tumor phantoms. CONCLUSIONS: This work demonstrates
      not only the superior benefits of a multi-modal feedback over traditional single
      modality feedback, but also the effectiveness of vibration in providing haptic
      feedback to artificial palpation systems.

PMID- 30187199
TI  - Colorectal endoscopic submucosal dissection using novel articulating devices: a
      comparative study in a live porcine model.
AB  - BACKGROUND AND AIMS: Colonic endoscopic submucosal dissection (ESD) is time
      consuming and bears a high risk of perforation. The aim of the present study was
      to compare the safety and efficacy between novel articulating devices and
      conventional ESD in live porcine colon models. METHODS: Thirty ESDs in ten pigs
      were carried out at three different locations (15, 25, and 35 cm from the anus)
      by the conventional method (n = 15) and by the new method (n = 15). Procedure
      times, adverse events (perforation, bleeding), and damage to the muscular layer
      were recorded, and the ESD time per unit area of the specimens was calculated.
      RESULTS: The perforation rate using the conventional method was 6.7% (1/15),
      whereas that using the new method was 0.0%. The number of sites of muscular
      damage was significantly lower in the new than conventional method (6 vs. 37,
      respectively; P = 0.024). The mean procedure time was significantly shorter in
      the new than conventional method (4.6 +/- 2.0 vs. 7.0 +/- 4.1 min/cm2,
      respectively; P = 0.042). CONCLUSIONS: Use of the new ESD method allows for
      reduced adverse events and a shortened resection time.

PMID- 30187200
TI  - Effect of combining a recruitment maneuver with protective ventilation on
      inflammatory responses in video-assisted thoracoscopic lobectomy: a randomized
      controlled trial.
AB  - BACKGROUND: We hypothesized that the addition of a recruitment maneuver to
      protective ventilation (PVRM) would result in lower pulmonary and systemic
      inflammatory responses than traditional ventilation or protective ventilation
      (PV) alone in patients undergoing lung surgery. METHODS: Sixty patients who
      underwent scheduled thoracoscopic lobectomy were randomly assigned to three
      groups: traditional ventilation, PV, or PVRM. Ventilations were performed using a
      tidal volume of 10 mL/kg for the traditional ventilation group and either 8 mL/kg
      (two-lung) or 6 mL/kg (one-lung, OLV) with a positive end-expiratory pressure of
      5 cm H2O for the PV and PVRM groups. The RM was performed 10 min after the start
      of OLV. Fiberoptic bronchoalveolar lavage (BAL) was performed twice in dependent
      and non-dependent lungs: before the start and immediately after the end of OLV.
      Blood samples were collected at the same time points. The levels of cytokines,
      including TNF-alpha, IL-1beta, IL-6, IL-8, and IL-10, were measured. RESULTS:
      After OLV, the level of TNF-alpha in the BAL fluid of dependent lungs was
      significantly higher in the PV than in the PVRM group (P = 0.049), whereas IL
      1beta, IL-6, IL-8, and IL-10 levels were not significantly different among the
      groups. In non-dependent lung BAL fluid, no cytokines were significantly
      different among the groups. After OLV, IL-10 serum levels were significantly
      higher in the traditional ventilation than in the PVRM group (P = 0.027).
      CONCLUSIONS: Lower inflammatory responses in the ventilated lung and serum were
      observed with PVRM than with traditional ventilation or PV alone. Larger multi
      center clinical trials are warranted to confirm the effects of different
      ventilatory strategies on postoperative outcomes.

PMID- 30187197
TI  - Role of the heat shock protein family in bone metabolism.
AB  - Heat shock proteins (HSPs) are a family of proteins produced by cells in response
      to exposure to stressful conditions. In addition to their role as chaperones,
      they also play an important role in the cardiovascular, immune, and other
      systems. Normal bone tissue is maintained by bone metabolism, particularly by the
      balance between osteoblasts and osteoclasts, which are physiologically regulated
      by multiple hormones and cytokines. In recent years, studies have reported the
      vital role of HSPs in bone metabolism. However, the conclusions remain largely
      controversial, and the exact mechanisms are still unclear, so a review and
      analyses of previous studies are of importance. This article reviews the current
      understanding of the roles and effects of HSPs on bone cells (osteoblasts,
      osteoclasts, and osteocytes), in relation to bone metabolism.

PMID- 30187201
TI  - Effectiveness and safety of endoscopic aspiration mucosectomy and endoscopic
      submucosal dissection in patients with superficial esophageal squamous-cell
      carcinoma.
AB  - BACKGROUND: Endoscopic submucosal dissection (ESD) has been performed in a high
      proportion of patients with superficial esophageal squamous-cell carcinoma.
      Endoscopic aspiration mucosectomy (EAM) is a more straightforward technique that
      is easier to perform. We retrospectively evaluated the safety and efficacy of EAM
      and ESD to clarify the advantages and disadvantages of each procedure. METHODS: A
      total of 374 patients (423 lesions) who underwent endoscopic resection were
      retrospectively studied. The following variables were evaluated (1) procedure
      time and adverse events as safety, and (2) en bloc complete resection rate, local
      recurrence rate, lymph node recurrence rate, overall survival rate, and cause
      specific survival rate as efficacy. RESULTS: EAM was performed in 134 patients
      (149 lesions), and ESD was performed in 240 patients (274 lesions). The procedure
      times of EAM and ESD were 31.0 +/- 22.4 and 85.7 +/- 46.5 min (p < 0.001),
      respectively. The perforation rates were 0 and 6.2% (p = 0.002), respectively.
      The en bloc complete resection rates were 48.3 and 91.6% (p < 0.001),
      respectively. The local recurrence rates were 5.5 and 0% (p < 0.001),
      respectively. For lesions measuring less than 15 mm in diameter, EAM had a
      relatively good en bloc complete resection rate (EAM, 76.1% vs. ESD, 100%) and a
      significantly short procedure time (EAM, 25.2 +/- 15.2 min vs. ESD, 62.7 +/- 35.2
      min; p < 0.001). CONCLUSIONS: ESD has a higher en bloc complete resection rate
      and a better local control rate than EAM. For lesions measuring less than 15 mm
      in diameter, EAM may be a treatment option.

PMID- 30187202
TI  - Surgical phase modelling in minimal invasive surgery.
AB  - BACKGROUND: Surgical Process Modelling (SPM) offers the possibility to
      automatically gain insight in the surgical workflow, with the potential to
      improve OR logistics and surgical care. Most studies have focussed on phase
      recognition modelling of the laparoscopic cholecystectomy, because of its
      standard and frequent execution. To demonstrate the broad applicability of SPM,
      more diverse and complex procedures need to be studied. The aim of this study is
      to investigate the accuracy in which we can recognise and extract surgical phases
      in laparoscopic hysterectomies (LHs) with inherent variability in procedure time.
      To show the applicability of the approach, the model was used to automatically
      predict surgical end-times. METHODS: A dataset of 40 video-recorded LHs was
      manually annotated for instrument use and divided into ten surgical phases. The
      use of instruments provided the feature input for building a Random Forest
      surgical phase recognition model that was trained to automatically recognise
      surgical phases. Tenfold cross-validation was performed to optimise the model for
      predicting the surgical end-time throughout the procedure. RESULTS: Average
      surgery time is 128 +/- 27 min. Large variability within specific phases is seen.
      Overall, the Random Forest model reaches an accuracy of 77% recognising the
      current phase in the procedure. Six of the phases are predicted accurately over
      80% of their duration. When predicting the surgical end-time, on average an error
      of 16 +/- 13 min is reached throughout the procedure. CONCLUSIONS: This study
      demonstrates an intra-operative approach to recognise surgical phases in 40
      laparoscopic hysterectomy cases based on instrument usage data. The model is
      capable of automatic detection of surgical phases for generation of a solid
      prediction of the surgical end-time.

PMID- 30187204
TI  - Safety and efficacy of using a short tunnel versus a standard tunnel for peroral
      endoscopic myotomy for Ling type IIc and III achalasia: a retrospective study.
AB  - BACKGROUND AND AIMS: Peroral endoscopic myotomy (POEM) for patients with Ling
      type IIc and III achalasia is associated with a high rate of adverse events.
      Decreasing the lengths of the tunnel and myotomy may be an effective method for
      reducing this rate. This study aimed to assess the safety and efficacy of using a
      short tunnel versus a standard tunnel for POEM. METHOD: We conducted a
      retrospective study of 126 patients with Ling type IIc and III achalasia
      undergoing POEM from January 2013 to December 2016. These patients were divided
      into a short tunnel group (n = 63) and a standard tunnel group (n = 63). The
      clinical efficacy of the procedure, operative time, length of the tunnel, length
      of myotomy and rates of adverse events were analyzed. RESULTS: The preoperative
      features were similar in both groups. No significant differences were found
      between the two groups in Eckardt score change, lower esophageal sphincter (LES)
      basal pressure or residual pressure after POEM (all p > 0.05). The mean lengths
      of the tunnel and myotomy were 7.6 cm and 4.8 cm, respectively, in the short
      tunnel group and 11.8 cm and 9.2 cm, respectively, in the standard tunnel group.
      The mean operative time of the short tunnel group was significantly shorter than
      that of the standard tunnel group (39.5 min vs. 48.2 min, respectively, p =
      0.001). A significant difference was observed in the rates of procedure-related
      adverse events between the two groups (9.5% vs. 33.3%, p = 0.001). CONCLUSION:
      The efficacy of the procedure was comparable between the two groups. However, the
      short tunnel significantly reduced the operation time and the rates of procedure
      related adverse events.

PMID- 30187203
TI  - The crossover technique for intracorporeal esophagojejunostomy following
      laparoscopic total gastrectomy: a simple and safe technique using a linear
      stapler and two barbed sutures.
AB  - BACKGROUND: Totally laparoscopic gastrectomy (LG) is preferred over open
      gastrectomy because it allows safe anastomosis, a small wound, and early bowel
      recovery. However, esophagojejunostomy (EJS) following laparoscopic total
      gastrectomy (LTG) remains technically challenging. To popularize LTG, a secure
      method of reconstruction must be developed. We present a simple and safe
      technique for intracorporeal EJS following LTG. METHODS: Our modified technique
      for intracorporeal EJS as a part of Roux-en-Y reconstruction following LTG
      incorporates an isoperistaltic stapled EJS with closure of the entry hole using
      two unidirectional barbed sutures. First, a side-to-side isoperistaltic EJS is
      created between the dorsal and left side of the esophagus and the jejunal arm.
      Second, the opening for the stapler is closed with a two-layer continuous suture
      using two 15-cm 3-0 V-Loc suture devices. The full-thickness inner layer closure
      commences from the sides of the staple lines and progresses toward the center of
      the enterotomy. During suturing, the remaining thread is utilized to apply
      tension and lift the enterotomy. Once the full-thickness layer closure is
      complete at the center of the enterotomy, suturing of the second seromuscular
      layer is started in the forward direction toward each corner to give a crossover
      shaped suturing line. RESULTS: From February 2012 to October 2017, 27 patients
      with gastric cancer underwent LTG with intracorporeal stapled EJS as a part of
      Roux-en-Y reconstruction. All procedures were successfully performed without any
      intra- or postoperative anastomosis-related complications. No conversion to other
      procedures was required. The mean suturing time was 19.1 +/- 9.5 min. The mean
      postoperative time to tolerating a liquid diet was 3.3 days, and the mean
      hospital stay was 12.1 days. CONCLUSIONS: We herein report our procedure for
      intracorporeal EJS using a linear stapler and barbed sutures. This technique is
      simple and feasible and has acceptable morbidity.

PMID- 30187205
TI  - Polymorphisms of Genes Related to Function and Metabolism of Vitamin D in
      Esophageal Adenocarcinoma.
AB  - PURPOSE: The vitamin D receptor (VDR) endocrine system has emerged as an
      endogenous pleiotropic biological cell regulator with anti-neoplastic effects on
      breast, colorectal, and prostatic adenocarcinomas. We studied the association of
      gene expression, polymorphisms of VDR, CYP27B1, and CYP24A1 genes and serum
      vitamin D levels as surrogate markers of disease progression in patients with
      acid reflux, Barrett's esophagus (BE), or esophageal adenocarcinoma (EAC).
      METHODS: We analyzed blood and tissue samples from patients with biopsy-confirmed
      BE or EAC for vitamin D levels, gene expressions, and polymorphisms in VDR (FokI
      [F/f], BsmI [B/b], ApaI [A/a], and TaqI [T/t]), CYP27B1 (HinfI [H/h]), and
      CYP24A1 (Hpy1881 [Y/y]). Percentages of homozygous dominant/recessive or
      heterozygous traits were assessed for each polymorphism in all patient subgroups.
      RESULTS: Genomic Bb and FF polymorphisms were highly prevalent in EAC patients,
      whereas BE patients had a high prevalence of wild-type Hpy1881 (YY polymorphism).
      Some polymorphisms (Yy for CYP24A1, bb for VDR) were noted only in EAC patients.
      Yy and bb forms were both uniquely present in some EAC patients without
      associated Barrett's lesions, but not in patients with concomitant BE. AA and bb
      polymorphisms were associated with decreased response to neoadjuvant therapy. A
      high level of VDR and CYP24A1 mRNA expression was observed in EAC tissue of non
      responders. Serum vitamin D deficiency was common in EAC patients. CONCLUSIONS:
      Specific polymorphisms in vitamin D metabolism-related genes are associated with
      the likelihood of reflux-BE-EAC progression. Identifying such polymorphisms may
      aid in development of better surveillance and diagnostic and therapeutic
      protocols.

PMID- 30187206
TI  - Age specificity in fornix-to-hippocampus association.
AB  - Both white and grey matter atrophy with age, but it is still unclear how decline
      in white matter relates to decline in grey matter, and how this relationship
      varies with age. In a group of healthy adults from 20 to 80 years old, divided
      into three age groups by tertiles, we cross-sectionally examined the white-to
      grey matter associations in the fornix and the hippocampus, and tested if and how
      the fornix-to-hippocampus relationship differs across the age groups. Both
      structures were also tested as predictors for performance on a memory test, the
      Selective Reminding Task (SRT). Participants were imaged with T1-weighted
      magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI), from which
      the hippocampal volume, fractional anisotropy (FA), and mean diffusivity (MD) for
      the bilateral crus and body of the fornix were calculated. Our data showed that
      even after accounting for age, sex, and motion parameters, fornix integrity
      predicted hippocampal volume in the two older age groups (middle and old age) for
      the crus of the fornix, and only in the oldest age group for the body of the
      fornix. Furthermore, fornix integrity significantly predicted SRT performance,
      whereas hippocampal volume did not; this relationship was also observed only in
      the oldest age group, and absent in the two younger age groups. The age
      specificity of the relationships suggests that the fornix-to-hippocampus
      relationship only manifests once brain structures begin to atrophy in old age,
      and that fornix integrity is a more sensitive measure for episodic memory than is
      hippocampal volume.

PMID- 30187207
TI  - Human papillomavirus and colorectal cancer.
AB  - The involvement of human papillomavirus in carcinogenesis of colorectal cancer is
      a contentious issue. The presented meta-analysis was performed to systematize the
      currently available research results on the matter. The analysis was based on the
      data from 19 studies to assess the association of HPV infection with colorectal
      cancer. According to the obtained data, researchers determined the statistically
      significant level of HPV infection in tumor tissue of CRC and the resulting
      relative risk of developing CRC with HPV infection to be RR (95% CI) = 2.97 (1.42
      6.22) with p = 0.0039.

PMID- 30187209
TI  - Robot-assisted abdominal wall excision of a PSMA-detected prostate cancer
      metastasis.
AB  - Recent advances in novel functional imaging techniques such as PSMA PET may now
      offer the ability to identify small volume metastases which may otherwise go
      undetected. The treatment of these lesions is controversial, particularly in the
      oligometastatic state. We report the case of an abdominal wall metastasis
      detected with PSMA imaging which we treated with surgical excision. This resulted
      in an undetectable PSA 6 weeks post excision.

PMID- 30187208
TI  - Effect of environmental variables on phytonutrients of Origanum vulgare L. in the
      sub-humid region of the northwestern Himalayas.
AB  - Ecological and soil physiochemical parameters impact the crop quality and
      development. In spite of the huge commercial prospective, the phytonutrient and
      chemometric profiles of Himalayan oregano (Origanum vulgare L.) have not been
      evaluated, and their relationships with ecological parameters are still lacking.
      The objective of this research study was to evaluate the disparity in the
      phytonutrient profiles of different ecotypes of O. vulgare in wild and cultivated
      populations and determine whether such variation was related to the diverse
      climatic and edaphic conditions prevailing in the northwestern Himalayas.
      Micrometeorological, atomic absorption spectroscopy for micro-elemental analysis
      was determined for soil. HPLC was used to determine the disparity in
      phytonutrient (quercetin, betacarotene, ascorbic acid, and catechin) and
      phytochemical (arbutin) levels. Cultivated populations had lower phytonutrient
      levels than wild populations. The habitat exhibiting pH values ranging from 6 to
      7 elevated organic carbon (2.42%), nitrogen (97.41 kg ha-1), and manganese (10-12
      MUg g-1) and zinc contents (0.39-0.50%) show luxirant growth of Origanum
      vulgarel. The phytonutrient (quercetin, betacarotene, ascorbic acid, arbutin, and
      catechin) levels had a direct relationship with UV-B flux (r2 = 0.82) and
      potassium (r2 = 0.97). Wild accessions predominantly contained catechin and
      ascorbic acid, with maximum values of 163.8 and 46.88 MUg g-1, respectively,
      while the cultivated accessions had the highest level of arbutin (53.42 MUg g-1).
      Maximum variation was observed in quercetin (114.61%) followed by beta-carotene
      (87.53%). Cultivated accessions had less quercetin (0.04-1.25 MUg g-1) than wild
      accessions (1.25-2.87 MUg g-1). Wild accessions had higher phytonutrient values
      for catechin, beta-carotene, and ascorbic acid while cultivated accessions had
      maximum values for arbutin. The correlation of environmental variables with
      phytonutrient levels paves the way for metabolomic-guided enhancement of
      agricultural practices for better herb quality.

PMID- 30187211
TI  - A colorimetric assay for acetylcholinesterase activity and inhibitor screening
      based on the thiocholine-induced inhibition of the oxidative power of MnO2
      nanosheets on 3,3',5,5'-tetramethylbenzidine.
AB  - The authors describe a colorimetric method for the determination of the activity
      of acetylcholinesterase (AChE). Manganese dioxide (MnO2) nanosheets directly
      reacts with 3,3',5,5'-tetramethylbenzidine (TMB) in the absence of hydrogen
      peroxide (H2O2). This leads to the formation of a blue product (oxTMB) with an
      absorption peak at 652 nm. If AChE hydrolyzes its substrate acetylthiocholine
      chloride, thiocholine is formed which blocks the oxidative power of the MnO2
      nanosheets. Hence, oxTMB will not be formed. The decreased absorbance is directly
      related to the AChE activity in the 0.01-1.0 mU.mL-1 range. The detection limit
      is 0.01 mU.mL-1 and the relative standard deviation is 1.2% (for n = 11 at 0.5
      mU.mL-1). The method was also applied to screen for inhibitors of AChE. Graphical
      abstract Based on the oxidizing properties of manganese dioxide nanosheets (MnO2
      nanosheets), we report a colorimetric method for determining acetylcholinesterase
      activity with the chromogenic substrate 3,3',5,5'-tetramethylbenzidine (TMB).

PMID- 30187210
TI  - Overall survival of Brazilian acute myeloid leukemia patients according to the
      European LeukemiaNet prognostic scoring system: a cross-sectional study.
AB  - Prognostic stratification in acute myeloid leukemia (AML) relies, mostly, on
      cytogenetics and molecular features of leukemic blasts. The LeukemiaNet
      prognostic scoring system has been proposed as a standardized way of evaluating
      prognosis in AML. We have analysed outcomes in 65 AML cases (median age of 54
      years, range 18-82) treated at five hematology centers in Brazil stritified
      according to the European Leukemia Net (ELN) recommendations for cytogenetic and
      molecular analysis. We classified patients as favorable (N = 13), intermediate-1
      (N = 25), intermediate-2 (N = 15), or adverse risk (N = 9). Bone marrow
      transplantation (BMT) was performed in 13 patients (21%). Median follow-up was 12
      months. The median overall survival (OS) for all patients was 12.4 months. Median
      OS was 19.8, 12.4, 10.1, and 10.4 months (p = 0.24) for patients in the
      favorable, intermediate-1, intermediate-2, and adverse groups, respectively.
      Among patients receiving BMT, median OS was 26.8 months. The ELN is a valuable
      tool for prognostic stratification of AML patients treated in Brazil.
      Nevertheless, its usefulness is limited when compared to data from developed
      countries.

PMID- 30187213
TI  - Correction to: mTOR co-targeting strategies for head and neck cancer therapy.
AB  - The author's name was tagged incorrectly in XML. "Silvio Gutkind J" should be
      tagged as "J. Silvio Gutkind". Given name is "J. Silvio" and the Family name is
      "Gutkind".

PMID- 30187212
TI  - Zn2+-binding in the glutamate-rich region of the intrinsically disordered protein
      prothymosin-alpha.
AB  - Prothymosin-alpha is a small, multifunctional intrinsically disordered protein
      associated with cell survival and proliferation which binds multiple Zn2+ ions
      and undergoes partial folding. The interaction between prothymosin-alpha and at
      least two of its protein targets is significantly enhanced in the presence of
      Zn2+ ions, suggesting that Zn2+ binding plays a role in the protein's function.
      The primary sequence of prothymosin-alpha is highly acidic, with almost 50%
      comprised of Asp and Glu, and is unusual for a Zn2+-binding protein as it lacks
      Cys and His residues. To gain a better understanding of the nature of the Zn2+
      prothymosin-alpha interactions and the protein's ability to discriminate Zn2+
      over other divalent cations (e.g., Ca2+, Co2+, Mg2+) we synthesized a set of
      three model peptides and characterized the effect of metal binding using
      electrospray ionization mass spectrometry (ESI MS) and circular dichroism (CD)
      spectroscopy. ESI MS data reveal that the native peptide model of the glutamic
      acid rich region binds 4 Zn2+ ions with apparent, stepwise Kd values that are, at
      highest, in the tens of micromolar range. A peptide model with the same amino
      acid composition as the native sequence, but with the residues arranged randomly,
      showed no evidence of structural change by CD upon introduction of Zn2+. These
      results suggest that the high net negative charge of the glutamic acid-rich
      region of prothymosin-alpha is not a sufficient criterion for Zn2+ to induce a
      structural change; rather, Zn2+ binding to prothymosin-alpha is sequence
      specific, providing important insight into the behavior of intrinsically
      disordered proteins.

PMID- 30187214
TI  - Recent Findings of the Comparative Efficacy and Tolerability of Antidepressants
      for Major Depressive Disorder: Do We Now Know What to Prescribe?

PMID- 30187215
TI  - Ki67 and P53 in Relation to Disease Progression in Metastatic Pancreatic Cancer:
      a Single Institution Analysis.
AB  - We investigated the expression patterns of Ki67 and p53 in metastatic pancreatic
      adenocarcinomas and analyzed their relationship with disease progression-free
      survival (PFS) and overall survival (OS) in the overall study population and in
      patients treated with a gemcitabine-containing chemotherapy versus FOLFIRINOX
      chemotherapy. Patients with histologically confirmed stage IV adenocarcinoma of
      the pancreas treated at AUBMC were included after obtaining institutional review
      board approval (IRB ID: IM.ST.05). The ROC was plotted to identify the threshold
      Ki-67, p53 and CA19-9 value for disease progression, the identified value was
      further used in Kaplan Meier curves to compare PFS for both groups (gemcitabine
      versus FOLFIRINOX). A value of p < 0.05 was considered significant in all
      analyses. On univariate analysis, patients who had a Ki-67 > 12.5% or a p53 > 15%
      had significantly shorter PFS (p = 0.034 and p = 0.016, respectively). This
      effect was restricted to Gemcitabine or gemcitabine-combination treated patients.
      A decrease in CA19-9 levels 6-8 weeks after chemotherapy of >58% had
      significantly longer PFS (p = 0.027). On multivariate analysis after controlling
      for grade, age and P53, Ki-67 remained significant, for every one unit increase
      in Ki-67 the progression risk increases by 1.017 times. Our study highlights the
      negative impact of high P53 expression and Ki67 proliferation index on PFS in
      patients with metastatic pancreatic cancer.

PMID- 30187216
TI  - Clinical benefits of introducing real-time multiplex PCR for cerebrospinal fluid
      as routine diagnostic at a tertiary care pediatric center.
AB  - BACKGROUND: Sepsis-like illness with suspected meningitis or encephalitis is a
      common reason for using empiric antimicrobial therapy in infants and children.
      However, in cases of viral meningitis not covered by these antimicrobials, this
      management is ineffective and due to side effects potentially harmful. METHODS: A
      retrospective analysis of cerebrospinal fluid (CSF) multiplex PCRs (Biofire
      FilmArray(r)) in children with clinical suspicion of meningitis, encephalitis or
      sepsis-like illness was performed over the period of 1 year. Subsequently, a
      subgroup of children (age of 8-84 days of life) diagnosed with viral meningitis
      (enterovirus, HHV-6, human parechovirus) was compared to an age-matched control
      group. RESULTS: During the study period, the multiplex PCR panel was performed on
      187 individual CSF samples that met the inclusion criteria. About half of the
      patients (92/187) were less than 1 year of age. In 27 cases (14.4%), the PCR
      yielded a positive result with the majority (12/27) being indicative of an
      enteroviral infection. In the age group of 8-84 days of life, 36.4% of the
      patients had a positive result. When the patients with a PCR positive for a viral
      agent were compared to an age-matched group of patients, no differences were
      observed regarding symptoms and laboratory parameters. However, the duration of
      antimicrobial therapy could be significantly reduced through the use of multiplex
      PCR. CONCLUSION: The use of on-site diagnostic multiplex PCR was able to reduce
      the use of antimicrobials in selected cases. This test can guide clinical
      decisions earlier during the course of medical care compared to standard
      diagnostics.

PMID- 30187217
TI  - Primary ecthyma gangraenosum due to central venous catheter-related bloodstream
      infection with Pseudomonas aeruginosa.

PMID- 30187218
TI  - Elizabethkingia meningoseptica diagnostic hitch.

PMID- 30187219
TI  - Intracranial foreign material granulomas after cranial surgery.
AB  - BACKGROUND: Various synthetic materials are used in neurosurgery and left in
      place intentionally during surgery for several purposes such as hemostasis, dural
      closure, or cranioplasty. Although leaving such substances in surgical sites is
      considered safe, in general, foreign body granuloma may occur months or years
      after intracranial surgery. Thus, far relatively little is known about treatment
      and outcome of such lesions. METHODS: A systematic review of 3466
      histopathological examinations after cranial surgeries achieved over a 13-year
      period was performed. After excluding patients with Teflon granulomas or
      infection, a total of 12 patients with foreign body granulomas induced by
      synthetic material used in a prior surgery were identified. Patient records,
      imaging studies, and histopathological data were analyzed. Furthermore,
      postoperative outcome was assessed. RESULTS: Mean age at the second surgery was
      51 years (range, 11-68 years). The median time between the primary and the
      secondary surgery was 13 months (range, 1-545 months). Eight patients (75%)
      presented with signs and symptoms related to the foreign body granulomas. Total
      resection of the foreign body granulomas was performed in all patients. The
      granulomas were induced by oxidized cellulose polymer (n = 6), suture material (n
      = 3), Gelfoam (n = 1), methylmethacrylate (n = 1), and bone wax (n = 1). The mean
      postoperative follow-up time was 54 months (range 1-137 months). There was
      symptomatic improvement in all instances. Imaging studies did not demonstrate any
      recurrence. CONCLUSION: Despite its rarity, foreign body granuloma should be
      taken into consideration in the differential diagnosis of intracranial mass
      lesions especially in cases of suspected tumor recurrence after prior surgery.
      The pathogenesis of foreign body granuloma still needs further clarification. Our
      study demonstrates that they have good prognosis after surgical removal.

PMID- 30187220
TI  - Extended duration of dilator use beyond 1 year may reduce vaginal stenosis after
      intravaginal high-dose-rate brachytherapy.
AB  - BACKGROUND: Vaginal dilators (VD) are recommended following vaginal or pelvic
      radiotherapy for patients with endometrial carcinoma (EC) to prevent vaginal
      stenosis (VS). The time course of VS is not fully understood and the optimal
      duration of VD use is unknown. METHODS: We reviewed 243 stage IA-II EC patients
      who received adjuvant brachytherapy (BT) at an academic tertiary referral center.
      Patients were instructed to use their VD three times per week for at least 1-year
      duration. The primary outcome was development of grade >= 1 VS using CTCAEv4
      criteria during the follow-up period. The log-rank test and multivariable Cox
      proportional hazards modeling were used to evaluate the effect of VD use
      (noncompliance vs. standard compliance [up to 1 year] vs. extended compliance
      [over 1 year]) on VS. RESULTS: The median follow-up was 15.2 months over the 5
      year study period. At 15 months, the incidence of VS was 38.8% for noncompliant
      patients, 33.5% for those with standard compliance, and 21.4% for those with
      extended compliance (median time to grade >= 1 VS was 17.5 months, 26.7 months,
      and not yet reached for these groups, respectively). On multivariable Cox
      regression analysis, extended compliance remained a significant predictor of
      reduced VS risk when compared to both noncompliance (HR 0.38, 95% CI 0.18-0.80, p
      = 0.012) and standard compliance (HR 0.43, 95% CI 0.20-0.89, p = 0.023).
      CONCLUSIONS: The risk of VS persists beyond 1 year after BT. Extended VD
      compliance beyond 1 year may mitigate this risk.

PMID- 30187221
TI  - Exploring reasons behind patient compliance with nutrition supplements before
      pelvic exenteration surgery.
AB  - PURPOSE: Compliance with oral nutrition support (ONS) is poorly reported in the
      literature. Many factors influence compliance, which could mask the true benefits
      of preoperative ONS. Surgical oncology patients, including pelvic exenteration
      patients, are often requested by healthcare workers to consume nutrition
      supplements before surgery. Exploration of barriers and enablers to compliance
      with nutrition supplements is needed to improve patient compliance and understand
      the real impact of preoperative ONS. METHOD: A qualitative study using semi
      structured interviews was performed to investigate enablers and barriers to
      preoperative nutrition supplement compliance. Twenty participants who had been
      asked to consume 15 nutrition supplements, either immunonutrition or standard
      polymeric supplements, were interviewed. Inductive thematic analysis was used to
      determine major themes associated with compliance. RESULTS: Twelve out of 20
      participants were not compliant with recommended dosing. Well-nourished
      participants were more compliant than malnourished participants. Major themes
      associated with compliance were flavour, volume, texture, impact on dietary
      intake and motivation to consume supplements. Flavour differed between the two
      groups, negatively impacting compliance in the immunonutrition group. Volume,
      texture and impact on dietary intake also negatively impacted compliance whereas
      motivation positively impacted compliance. CONCLUSION: To overcome barriers and
      enforce enablers with nutrition supplement compliance, it is essential healthcare
      workers implement individualised interventions, taking into account nutritional
      status. A range of flavours, minimal volume and low viscosity supplements should
      be provided to address individual preference and minimise poor compliance. Better
      targeted education and regular motivation are needed to improve compliance.

PMID- 30187223
TI  - Sensitivity analysis of the Poisson Nernst-Planck equations: a finite element
      approximation for the sensitive analysis of an electrodiffusion model.
AB  - Biological structures exhibiting electric potential fluctuations such as neuron
      and neural structures with complex geometries are modelled using an
      electrodiffusion or Poisson Nernst-Planck system of equations. These structures
      typically depend upon several parameters displaying a large degree of variation
      or that cannot be precisely inferred experimentally. It is crucial to understand
      how the mathematical model (and resulting simulations) depend on specific values
      of these parameters. Here we develop a rigorous approach based on the sensitivity
      equation for the electrodiffusion model. To illustrate the proposed methodology,
      we investigate the sensitivity of the electrical response of a node of Ranvier
      with respect to ionic diffusion coefficients and the membrane dielectric
      permittivity.

PMID- 30187222
TI  - Using patient-reported religious/spiritual concerns to identify patients who
      accept chaplain interventions in an outpatient oncology setting.
AB  - PURPOSE: The goals of this study were to (1) describe the prevalence and
      correlates of patient-reported religious/spiritual (R/S) needs in outpatient
      oncology patients and (2) estimate the associations of R/S concerns with
      acceptance of an R/S intervention offered by phone. METHODS: This was a
      retrospective analysis of data collected from distress screenings and spiritual
      care interventions at an outpatient cancer center from March 1, 2017 to May 9,
      2017. Patients (n = 1249) used a tablet to self-report the following R/S
      concerns: spiritual or religious concern, isolation, struggle to find
      hope/meaning in life, concern for family, fear of death, shame/guilt, and doubts
      about faith. Patients were also screened for anxiety, depression, and distress. A
      chaplain contacted patients that reported one or more R/S concerns to offer R/S
      interventions via telephone or in person. RESULTS: Approximately one third
      (29.9%) of surveyed patients indicated at least one R/S need. Younger age, female
      gender, anxiety, depression, and distress were associated with indication of
      specific R/S concerns. Fear of death (OR 1.64 [1.02, 2.66], p = 0.043), struggle
      to find meaning/hope in life (OR 2.47 [1.39, 4.39], p = 0.002), and anxiety (p =
      1.003) were associated with increased odds of intervention acceptance.
      CONCLUSION: Effective screening practices are needed for chaplains to prioritize
      patients most in need. This exploratory study suggests that screening for
      struggle to find meaning/hope in life, fear of death, and anxiety will help
      chaplains identify patients who have R/S concerns and will likely accept R/S
      interventions. Developing effective telehealth practices like this is an
      important direction for the field.

PMID- 30187224
TI  - Generalized quasispecies model on finite metric spaces: isometry groups and
      spectral properties of evolutionary matrices.
AB  - The quasispecies model introduced by Eigen in 1971 has close connections with the
      isometry group of the space of binary sequences relative to the Hamming distance
      metric. Generalizing this observation we introduce an abstract quasispecies model
      on a finite metric space X together with a group of isometries [Formula: see
      text] acting transitively on X. We show that if the domain of the fitness
      function has a natural decomposition into the union of t G-orbits, G being a
      subgroup of [Formula: see text], then the dominant eigenvalue of the evolutionary
      matrix satisfies an algebraic equation of degree at most [Formula: see text],
      where R is the orbital ring that is defined in the text. The general theory is
      illustrated by three detailed examples. In the first two of them the space X is
      taken to be the metric space of vertices of a regular polytope with the natural
      "edge" metric, these are the cases of a regular m-gon and of a hyperoctahedron;
      the final example takes as X the quotient rings [Formula: see text] with p-adic
      metric.

PMID- 30187225
TI  - Large scale patterns in mussel beds: stripes or spots?
AB  - An aerial view of an intertidal mussel bed often reveals large scale striped
      patterns aligned perpendicular to the direction of the tide; dense bands of
      mussels alternate periodically with near bare sediment. Experimental work led to
      the formulation of a set of coupled partial differential equations modelling a
      mussel-algae interaction, which proved pivotal in explaining the phenomenon. The
      key class of model solutions to consider are one-dimensional periodic travelling
      waves (wavetrains) that encapsulate the abundance of peak and trough mussel
      densities observed in practice. These solutions may, or may not, be stable to
      small perturbations, and previous work has focused on determining the
      ecologically relevant (stable) wavetrain solutions in terms of model parameters.
      The aim of this paper is to extend this analysis to two space dimensions by
      considering the full stripe pattern solution in order to study the effect of
      transverse two-dimensional perturbations-a more true to life problem. Using
      numerical continuation techniques, we find that some striped patterns that were
      previously deemed stable via the consideration of the associated wavetrain
      solution, are in fact unstable to transverse two-dimensional perturbations; and
      numerical simulation of the model shows that they break up to form regular
      spotted patterns. In particular, we show that break up of stripes into spots is a
      consequence of low tidal flow rates. Our consideration of random algal movement
      via a dispersal term allows us to show that a higher algal dispersal rate
      facilitates the formation of stripes at lower flow rates, but also encourages
      their break up into spots. We identify a novel hysteresis effect in mussel beds
      that is a consequence of transverse perturbations.

PMID- 30187226
TI  - Sequence-based 5-mers highly correlated to epigenetic modifications in genes
      interactions.
AB  - One of the main concerns in biology is extracting sophisticated features from DNA
      sequence for gene interaction determination, receiving a great deal of
      researchers' attention. The epigenetic modifications along with their patterns
      have been intensely recognized as dominant features affecting on gene expression.
      However, studying sequenced-based features highly correlated to this key element
      has remained limited. The main objective in this research was to propose a new
      feature highly correlated to epigenetic modifications capable of classification
      of genes. In this paper, classification of 34 genes in PPAR signaling pathway
      associated with muscle fat tissue in human was performed. Using different
      statistical outlier detection methods, we proposed that 5-mers highly correlated
      to epigenetic modifications can correctly categorize the genes involved in the
      same biological pathway or process. Thirty-four genes in PPAR signaling pathway
      were classified via applying a proposed feature, 5-mers strongly associated to 17
      different epigenetic modifications. For this, diverse statistical outlier
      detection methods were applied to specify the group of thoroughly correlated
      genes. The results indicated that these 5-mers can appropriately identify
      correlated genes. In addition, our results corresponded to GeneMania interaction
      information, leading to support the suggested method. The appealing findings
      imply that not only epigenetic modifications but also their highly correlated 5
      mers can be applied for reconstructing gene regulatory networks as supplementary
      data as well as other applications like physical interaction, genes
      prioritization, indicating some sort of data fusion in this analysis.

PMID- 30187227
TI  - Impact of Glucose Measuring Systems and Sample Type on Diagnosis Rates of
      Diabetes Mellitus.
AB  - INTRODUCTION: The use of glucose point-of-care testing (POCT) devices for the
      diagnosis of diabetes mellitus (DM) is an ongoing controversy. In patient
      management, glucose concentrations are determined by POCT and core laboratory
      glucose methods, and the values are commonly compared even though the samples
      collected are different, namely, capillary whole blood and venous plasma. In
      individual patients it is difficult to distinguish between factors that can
      influence the results, such as sample type and measuring procedure. In this
      study, glucose concentrations obtained using POCT and core laboratory instruments
      were assessed to duplicate typical scenarios experienced in healthcare.
      Corresponding diagnosis rates of impaired glucose tolerance (IGT) and DM based on
      fixed, method-independent cutoffs were compared. METHODS: Glucose concentration
      was measured by the 2-h oral glucose tolerance test (OGTT) in samples collected
      from an inpatient cohort and a cohort from the general population. Two POCT
      methods, namely, a handheld unit-use glucometer and a small bench-top analyzer
      with batch reagents, and two core laboratory procedures were used to measure
      glucose concentrations. The sample types were whole blood and plasma samples
      collected from venous and capillary blood. The glycated hemoglobin level in whole
      blood was also determined. RESULTS: A total of 231 subjects were included in the
      study. The 2-h OGTT glucose concentrations in the capillary whole blood samples
      showed a positive bias of 0.8 mmol/L compared to those obtained using core
      laboratory plasma glucose methods, leading to increased rates of diabetes
      diagnosis. This bias decreased to 0.2 mmol/L when venous blood was used in the
      tests. A change in the method used by the core laboratory introduced a negative
      bias of 0.5 mmol/L and, consequently, a lower diagnosis rates. DISCUSSION AND
      CONCLUSION: Venous blood samples measured at the point-of-care are the most
      suitable sample type for the measurement of the glucose concentration in the 2-h
      OGTT. The investigated unit-use POCT method is suitable for the diagnosis of IGT
      and DM when venous blood samples are collected. Importantly, changes in
      measurement procedures can introduce a bias and affect diagnosis rates, thereby
      emphasizing the need for further harmonization of glucose methods. A plain
      language summary is available for this article.

PMID- 30187228
TI  - Hospitalization and mortality among pediatric cancer survivors: a population
      based study.
AB  - PURPOSE: We examined serious long-term outcomes among childhood cancer survivors
      using population-based data. METHODS: We used 1982-2014 Washington State data to
      compare hospitalization and/or death (including cause-specific) during up to 27
      years follow-up among all 5+ year childhood cancer survivors < 20 years at
      diagnosis (n = 3,152) and a sample of comparison children within birth cohorts,
      with assessment by cancer type and child/family characteristics. RESULTS: During
      follow-up (9 years median), 12% of survivors had hospitalizations; 4% died.
      Greatest absolute risks/1,000 person-years were for hospitalization/deaths due to
      cancers (8.1), infection (6.2), injuries (6.0), and endocrine/metabolic disorders
      (5.8). Hazard ratios (HR) and 95% confidence intervals (CI) for hospitalization
      (2.7, 95% CI 2.4-3.0) and any-cause death (14.7, 95% CI 11.3-19.1) were
      increased, and for all cause-specific outcomes examined, most notably cancer-
      (35.1, 95% CI 23.7-51.9), hematological- (6.7, 95% CI 5.3-8.5), nervous system-
      (6.4, 95% CI 5.2-7.8), and circulatory- (5.2, 95% CI 4.1-6.5) related outcomes.
      Hospitalizations occurred more often among females and those receiving radiation,
      with modest differences by urban/rural birth residence and race/ethnicity. Cause
      specific outcomes varied by cancer type. CONCLUSIONS: This study suggests
      increased risks for the rarely-studied outcomes of long-term fracture and injury,
      and confirms increased risks of selected other conditions among survivors. Multi
      state pooling of population-based data would increase the ability to evaluate
      outcomes for uncommon cancer types and by racial/ethnic groups under-represented
      in many studies.

PMID- 30187229
TI  - Novel antimicrobial peptides produced by Candida intermedia LAMAP1790 active
      against the wine-spoilage yeast Brettanomyces bruxellensis.
AB  - Brettanomyces bruxellensis negatively impacts on the sensorial quality of wine by
      producing phenolic compounds associated with unpleasant odors. Thus, the control
      of this spoilage yeast is a critical factor during the winemaking process. A
      recent approach used to biocontrol undesired microorganisms is the use of yeast
      released antimicrobial peptides (AMPs), but this strategy has been poorly applied
      to wine-related microorganisms. The aim of this study was to evaluate the
      antifungal capacity of Candida intermedia LAMAP1790 against wine-spoilage strains
      of B. bruxellensis and fermentative strains of Saccharomyces cerevisiae, and also
      to determine the chemical nature of the compound. The exposure of strains to the
      supernatant of C. intermedia saturated cultures showed antifungal activity
      against B. bruxellensis, without affecting the growth of S. cerevisiae. By
      fractionation and concentration of C. intermedia supernatants, it was determined
      that the antifungal activity was related to the presence of heat-labile peptides
      with molecular masses under 5 kDa. To our knowledge, this is the first report of
      AMPs secreted by C. intermedia that control B. bruxellensis. This could lead to
      the development of new biocontrol strategies against this wine-spoilage yeast.

PMID- 30187230
TI  - Simple colony PCR procedure for the filamentous actinobacteria Frankia.
AB  - Molecular analysis of the filamentous actinobacteria Frankia is laborious because
      of the slow growth rate and required biomass needed for these techniques. An
      efficient and simple colony PCR protocol for Frankia was developed that saved
      time for analysis of any Frankia strains growing on a plate. Previously, it took
      5-6 weeks to get the correct size Frankia colonies on plates and then a minimum
      of 5 weeks of growth in liquid culture for DNA extraction. With this technique,
      these colonies could be screened after 5-6 weeks of growth by colony PCR. The
      procedure used a combination of mechanical and heat treatments and required no
      added buffers or chemicals. Our results demonstrate rapid and efficient PCR.

PMID- 30187232
TI  - Spatial Inhomogeneity of Cardiac Norepinephrine Transport Protein and Meta
      [123I]Iodobenzylguanidine Uptake in Swine Myocardial Tissue.
AB  - PURPOSE: The aim of the present study was to evaluate the expression of the
      cardiac norepinephrine transporter (NET) in the left ventricle (LV) of healthy
      pigs and its relationship with regional meta-[123I]iodobenzylguanidine
      ([123I]MIBG) myocardial uptake. PROCEDURES: Experiments were performed on animals
      injected with [123I]MIBG and acquired 2 h later using an ultrafast CZT gamma
      camera to assess the regional myocardial uptake. After image acquisition, animals
      were euthanized; the heart was quickly excised and underwent to an ex vivo single
      photon emission tomography (SPECT) imaging. Four small samples of tissue were
      then harvested from mid-walls and apex of the left ventricle; NET densities were
      evaluated and further normalized for protein loading per cardiac region. RESULTS:
      Three variants of NET protein with different molecular weights were detected. The
      expression of NET was not homogenous in the LV, with the highest density in the
      inferior wall and the lowest one in the apical area. The regional in vivo
      [123I]MIBG uptake revealed an analogous trend, showing a good linear relationship
      with NET expression. Parallel results were obtained from the ex vivo study.
      CONCLUSION: This study elucidates the expression of three different variants of
      NET proteins into the left ventricular myocardium of a healthy pig. NET
      expression into the LV was not homogeneous and paralleled by differences in
      regional [123I]MIBG uptake. Moreover, the correlation and the agreement between
      measurements of regional expression of NET variants and [123I]MIBG uptake
      represent a relevant finding for inferences about NET expression in the context
      of clinical imaging.

PMID- 30187231
TI  - Clinical Characteristics and efficacy of chemotherapy in sclerosing epithelioid
      fibrosarcoma.
AB  - BACKGROUND: Sclerosing epithelioid fibrosarcoma (SEF) is a very rare soft tissue
      sarcoma subtype. Clinically it is an aggressive tumour; however, to our knowledge
      there are no published reports regarding the efficacy of chemotherapy in SEF.
      Therefore, the aim of this study was to document the outcome of a series of
      patients with SEF treated at a single referral centre with reference to systemic
      therapy. METHODS: A retrospective search of a prospectively maintained database
      was performed to identify all patients diagnosed with SEF between 1990 and 2017.
      The diagnosis was confirmed in each case by a dedicated soft tissue sarcoma
      pathologist. We analysed those with recurrent disease and the effect of systemic
      chemotherapy in the metastatic setting. RESULTS: Thirteen patients were
      identified, median overall survival from diagnosis and metastasis were 47.3 (95%
      CI 25.0-131.9) and 16.3 (95% CI 5.3-20.6) months, respectively. In total, 12
      (92.3%) patients developed metastatic disease of which 10 died of disease, 1 was
      lost to follow-up and 1 had recently commenced palliative treatment. Among the 10
      patients with metastatic disease, 7 received palliative chemotherapy. Palliative
      chemotherapy resulted in partial response in 1 patient, stable disease in 3
      patients and progressive disease in 3 patients. Median time to disease
      progression was 2.7 (95% CI 1.2-4.4) months. Two of 13 patients were treated with
      adjuvant chemotherapy, receiving 6 cycles of liposomal doxorubicin and 1 cycle of
      doxorubicin, respectively, with a metastasis-free survival of 28.2 and 7.1
      months, respectively. CONCLUSION: SEF is an aggressive sarcoma subtype with a
      poor outcome and with limited responsiveness to conventional chemotherapy.
      Patients with this subtype should be considered for participation in clinical
      trials with novel agents. Further investigation into the biology of this rare
      disease is required to improve outcomes.

PMID- 30187233
TI  - Association of Tumor [18F]FDG Activity and Diffusion Restriction with Clinical
      Outcomes of Rhabdomyosarcomas.
AB  - PURPOSE: To evaluate whether the extent of restricted diffusion and 2-deoxy-2
      [18F] fluoro-D-glucose ([18F]FDG) uptake of pediatric rhabdomyosarcomas (RMS) on
      positron emission tomography (PET)/magnetic resonance (MR) images provides
      prognostic information. PROCEDURE: In a retrospective, IRB-approved study, we
      evaluated [18F]FDG PET/CT and diffusion-weighted (DW) MR imaging studies of 21
      children and adolescents (age 1-20 years) with RMS of the head and neck. [18F]FDG
      PET and DW MR scans at the time of the initial tumor diagnosis were fused using
      MIM software. Quantitative measures of the tumor mass with restricted diffusion,
      [18F]FDG hypermetabolism, or both were dichotomized at the median and tested for
      significance using Gray's test. Data were analyzed using a survival analysis and
      competing risk model with death as the competing risk. RESULTS: [18F]FDG PET/MR
      images demonstrated a mismatch between tumor areas with increased [18F]FDG uptake
      and restricted diffusion. The DWI, PET, and DWI + PET tumor volumes were
      dichotomized at their median values, 23.7, 16.4, and 9.5 cm3, respectively, and
      were used to estimate survival. DWI, PET, and DWI + PET overlap tumor volumes
      above the cutoff values were associated with tumor recurrence, regardless of post
      therapy COG stage (p = 0.007, p = 0.04, and p = 0.07, respectively). CONCLUSION:
      The extent of restricted diffusion within RMS and overlap of hypermetabolism plus
      restricted diffusion predict unfavorable clinical outcomes.

PMID- 30187234
TI  - A systematic review of effectiveness and economic evaluation of Cardiohelp and
      portable devices for extracorporeal membrane oxygenation (ECMO).
AB  - In recent years, there have been substantial advancements in the development of
      different technologies for extracorporeal membrane oxygenation (ECMO) for in
      hospital and out of hospital applications. However the effectiveness of these
      devices is not clearly known. The objective of this study was to evaluate the
      cost-effectiveness of Cardiohelp compared to other portable ECMO devices. In this
      systematic review, we searched Medline (via Ovid), Embase, Pubmed, Cochrane
      Library, SCOPUS, CRD and NICE. Articles were assessed by two independent
      reviewers for eligibility and quality of the evidence. Studies which compared
      Cardiohelp to other ECMO devices were included. Seven out of 1316 publication
      were included in this review, three of them were clinical trials and four were
      observational studies. The majority of the studies had limited quality. According
      to the measures of safety, Cardiohelp had safer technological features, but on
      the other hand, was more complex to use. Considering the effectiveness,
      Cardiohelp was not statistically different from other technologies. Cardiohelp
      showed slightly better performance than Centrimag in terms of cost per patient
      and cost-effectiveness. However, when clinical criteria were used to select the
      patients with good prognosis to administer the ECMO, incremental cost utility
      ratios (ICURs) for both Cardiohelp and Centrimag were below the level of
      willingness-to-pay threshold. According to the measures of safety and
      effectiveness, ECMO with Cardiohelp was not considerably different from other
      evaluated technologies. Moreover, ECMO with Cardiohelp or Centrimag can be
      considered cost-effective, provided that the patients are selected carefully in
      terms of neurological outcomes.

PMID- 30187235
TI  - Mind Matters: Treatment Concerns Predict the Emergence of Antiretroviral Therapy
      Side Effects in People with HIV.
AB  - The aim of this analysis of historical data was to determine whether patients'
      pre-treatment beliefs about antiretroviral therapy (ART) predict the subsequent
      reporting of side effects. Data were collected as part of a prospective, 12-month
      follow-up study. Of 120 people starting ART, 76 completed follow-up assessments
      and were included in the analyses. Participants completed validated
      questionnaires assessing their beliefs about ART, beliefs about medicines in
      general, perceived sensitivity to adverse effects of medicines, depression and
      anxiety before initiating ART and after 1 and 6 months of treatment. Adherence
      was assessed at 1, 6 and 12 months. Pre-treatment concerns about ART were
      associated with significantly more side effects at 1 month (p < 0.05) and 6
      months (p < 0.005). Side effects at 6 months predicted low adherence at 12 months
      (p < 0.005). These findings have implications for the development of
      interventions to support patients initiating ART by providing a mechanism to pre
      empt and reduce side effects.

PMID- 30187237
TI  - Stochastic Resonance with Dynamic Compression Improves the Growth of Adult
      Chondrocytes in Agarose Gel Constructs.
AB  - Dynamic mechanical stimulation has been an effective method to improve the growth
      of tissue engineering cartilage constructs derived from immature cells. However,
      when more mature cell populations are used, results are often variable due to the
      differing responses of these cells to external stimuli. This can be especially
      detrimental in the case of mechanical loading. In previous studies, multi-modal
      mechanical stimulation in the form of stochastic resonance was shown to be
      effective at improving the growth of young bovine chondrocytes. Thus, the aim of
      this study was to investigate the short-term and long-term effects of stochastic
      resonance on two groups of bovine chondrocytes, adult (> 30 month) and juvenile
      (~ 18 months). While the juvenile cells outperformed the adult cells in terms of
      their anabolic response to loading, combined mechanical loading for both age
      groups resulted in greater matrix synthesis compared to compressive loading
      alone. In the adult cells, potential pathological tissue formation was evident
      with the presence of cell clustering. However, the presence of broad-band
      mechanical vibrations (alone or with compressive loading) appeared to mitigate
      this response and allow these cells to attain a growth response similar to the
      juvenile, unstimulated cells. Therefore, the use of stochastic resonance appears
      to show promise as a method to improve the formation and properties of tissue
      engineered cartilage constructs, irrespective of cell age.

PMID- 30187238
TI  - Development of a Functionally Equivalent Model of the Mitral Valve Chordae
      Tendineae Through Topology Optimization.
AB  - Ischemic mitral regurgitation (IMR) is a currently prevalent disease in the US
      that is projected to become increasingly common as the aging population grows. In
      recent years, image-based simulations of mitral valve (MV) function have improved
      significantly, providing new tools to refine IMR treatment. However, clinical
      implementation of MV simulations has long been hindered as the in vivo MV chordae
      tendineae (MVCT) geometry cannot be captured with sufficient fidelity for
      computational modeling. In the current study, we addressed this challenge by
      developing a method to produce functionally equivalent MVCT models that can be
      built from the image-based MV leaflet geometry alone. We began our analysis using
      extant micron-resolution 3D imaging datasets to first build anatomically accurate
      MV models. We then systematically simplified the native MVCT structure to
      generate a series of synthetic models by consecutively removing key anatomic
      features, such as the thickness variations, branching patterns, and chordal
      origin distributions. In addition, through topology optimization, we identified
      the minimal structural complexity required to capture the native MVCT behavior.
      To assess the performance and predictive power of each synthetic model, we
      analyzed their performance by comparing the mismatch in simulated MV closed
      shape, as well as the strain and stress tensors, to ground-truth MV models.
      Interestingly, our results revealed a substantial redundancy in the anatomic
      structure of native chordal anatomy. We showed that the closing behavior of
      complete MV apparatus under normal, diseased, and surgically repaired scenarios
      can be faithfully replicated by a functionally equivalent MVCT model comprised of
      two representative papillary muscle heads, single strand chords, and a uniform
      insertion distribution with a density of 15 insertions/cm2. Hence, even though
      the complete sub-valvular structure is mostly missing in in vivo MV images, we
      believe our approach will allow for the development of patient-specific complete
      MV models for surgical repair planning.

PMID- 30187236
TI  - Effects of the environment of a simulated shelter in a gymnasium on sleep in
      children.
AB  - Effects of the environment of a simulated shelter in a gymnasium on sleep were
      investigated in 20 healthy school-aged children. Measurements were obtained
      during a one-night stay in a school gymnasium during the summer (C). Activity
      levels were monitored using a wrist actigraph, and temperature and humidity of
      the bedrooms in the subjects' homes were monitored from 3 days before to 3 days
      after C. The subjects were asked to provide information regarding subjective
      sleep estimations and thermal sensations. The results for the days before C (BC),
      C, the first day after C (A1), and the second day after C (A2) were compared. The
      bedroom temperature was significantly lower on BC than on the other nights. No
      significant difference was observed in bedtime, whereas wake-up time was
      significantly earlier on C and later on A1 than on the other nights. Total sleep
      time was significantly decreased on C (3.6 h) and increased on A1 when compared
      to the other nights. Daytime nap was significantly increased on A1 when compared
      to the other days. Subjective estimation of sleep quality was decreased and sweat
      sensation before sleep was increased on C when compared to the other nights. The
      main reason for sleep disturbances on C was heat. These results indicate that the
      environment of the simulated shelter in the gymnasium severely disturbed sleep in
      children. The resulting loss of sleep was compensated for by increased nocturnal
      sleep time and daytime napping on the next day.

PMID- 30187240
TI  - Importance of extracardiac FDG uptake to diagnose cardiac sarcoidosis.

PMID- 30187239
TI  - Self-Seeded MOCVD Growth and Dramatically Enhanced Photoluminescence of
      InGaAs/InP Core-Shell Nanowires.
AB  - We report on the growth and characterization of InGaAs/InP core-shell nanowires
      on Si-(111) substrates by metal-organic chemical vapor deposition (MOCVD). The
      strain at the core-shell interface induced by the large lattice mismatch between
      the InGaAs core and InP shell materials has strong influence on the growth
      behavior of the InP shell, leading to the asymmetric growth of InP shell around
      the InGaAs core and even to the bending of the nanowires. Transmission electron
      microscopy (TEM) measurements reveal that the InP shell is coherent with the
      InGaAs core without any misfit dislocations. Furthermore, photoluminescence (PL)
      measurements at 77 K show that the PL peak intensity from the InGaAs/InP core
      shell nanowires displays a ~ 100 times enhancement compared to the only InGaAs
      core sample without InP shell due to the passivation of surface states and
      effective carrier confinement resulting from InP shell layer. The results
      obtained here further our understanding of the growth behavior of strained core
      shell heterostructure nanowires and may open new possibilities for applications
      in InGaAs/InP heterostructure nanowire-based optoelectronic devices on Si
      platform.

PMID- 30187241
TI  - 2-Year follow-up of a patient with CD36 deficiency and takotsubo cardiomyopathy.

PMID- 30187242
TI  - Development of mazF-based markerless genome editing system and metabolic pathway
      engineering in Candida tropicalis for producing long-chain dicarboxylic acids.
AB  - Candida tropicalis can grow with alkanes or plant oils as the sole carbon source,
      and its industrial application thus has great potential. However, the choice of a
      suitable genetic operating system can effectively increase the speed of metabolic
      engineering. MazF functions as an mRNA interferase that preferentially cleaves
      single-stranded mRNAs at ACA sequences to inhibit protein synthesis, leading to
      cell growth arrest. Here, we constructed a suicide plasmid named pPICPJ-mazF that
      uses the mazF gene of Escherichia coli as a counterselectable marker for the
      markerless editing of C. tropicalis genes to increase the rate of conversion of
      oils into long-chain dicarboxylic acids. To reduce the beta-oxidation of fatty
      acids, the carnitine acetyltransferase gene (CART) was deleted using the gene
      editing system, and the yield of long-chain acids from the strain was increased
      to 8.27 g/L. By two homologous single exchanges, the promoters of both the
      cytochrome P450 gene and the NADPH-cytochrome P450 reductase gene were
      subsequently replaced by the constitutively expressed promoter pGAP, and the
      production of long-chain dicarboxylic acids by the generated strain (C.
      tropicalis PJPP1702) reached 11.39 g/L. The results of fed-batch fermentation
      showed that the yield of long-chain acids from the strain was further increased
      to 32.84 g/L, which was 11.4 times higher than that from the original strain. The
      results also showed that the pPICPJ-mazF-based markerless editing system may be
      more suited for completing the genetic editing of C. tropicalis.

PMID- 30187245
TI  - Ergonomic study of donkeys administered with Pycnogenol(r) and subjected to
      packing during the hot-dry season in Northern Nigeria.
AB  - The aim of the study was to determine some ergonomic parameters of donkeys
      administered with Pycnogenol(r) (PYC) and subjected to packing during the hot-dry
      season in northern Nigeria. Fifteen donkeys served as experimental subjects.
      Group 1 (n = 5) donkeys were subjected to trekking only (control), group 2 (n =
      5) donkeys were subjected to packing (P-PYC), and group 3 (n = 5) were
      administered with PYC (10 mg/kg) and subjected to packing (P+PYC). Each group
      covered a distance of 10 km. Some ergonomic parameters were evaluated. The
      duration of work in control, P-PYC, and P+PYC donkeys were 170.0 +/- 10 min (2.8
      h), 126.6 +/- 6.7 min (2.1 h), and 112.0 +/- 3.9 min (1.9 h), respectively. The
      energy expenditure obtained for P-PYC group (88.3 +/- 9.8 KJ/s) was significantly
      higher than the values of 28.3 +/- 3.7 KJ/s and 73.5 +/- 9.9 KJ/s obtained in
      control and P+PYC groups, respectively. The output was significantly higher in
      P+PYC group with the value of 5263.2 +/- 135 m/h. In conclusion, packing the
      donkeys during the hot-dry season was stressful; however, PYC may have served as
      a potent antifatigue agent to reduce the stress.

PMID- 30187244
TI  - Controlled Synthesis and Selective Adsorption Properties of Pr2CuO4 Nanosheets: a
      Discussion of Mechanism.
AB  - Tetragonal-phase Pr2CuO4 nanosheets with a thickness of about 60 nm were
      synthesized using the coordination compound methods (CCMs), then used as highly
      efficient selective adsorbent towards malachite green (MG) in aqueous solutions.
      The Pr2CuO4 samples were characterized using X-ray diffraction (XRD), scanning
      electron microscopy (SEM), high-resolution transmission electron microscopy
      (HRTEM), X-ray photoelectron spectroscopy (XPS), UV-Vis diffuse reflectance
      spectrum (DRS), and standard Brunauer-Emmett-Teller (BET) methods. The maximum
      adsorption capacity (Qm) of as-prepared samples was determined by adsorption
      isotherms with different adsorbent doses (m) of 0.03-0.07 g at 298, 318, and 338
      K based on the Langmuir model. When m < 0.03 g or > 0.07 g, effects of systemic
      mass loss and particle aggregation were discussed on the data deviation from the
      Langmuir model at 298 K. Based on the hydrogen bond and coordination bond, a
      possible mechanism of selective adsorption of MG by Pr2CuO4 is proposed, which
      was further verified by the adsorption experiments of CuO and Pr2O3 towards MG
      and competing-ion experiments. Finally, the theoretic studies were performed at
      DFT level to reveal the possible adsorption process.

PMID- 30187243
TI  - Transcriptomic and proteomic changes from medium supplementation and strain
      evolution in high-yielding Clostridium thermocellum strains.
AB  - Clostridium thermocellum is a potentially useful organism for the production of
      lignocellulosic biofuels because of its ability to directly deconstruct cellulose
      and convert it into ethanol. Previously engineered C. thermocellum strains have
      achieved higher yields and titers of ethanol. These strains often initially grow
      more poorly than the wild type. Adaptive laboratory evolution and medium
      supplementation have been used to improve growth, but the mechanism(s) by which
      growth improves remain(s) unclear. Here, we studied (1) wild-type C.
      thermocellum, (2) the slow-growing and high-ethanol-yielding mutant AG553, and
      (3) the faster-growing evolved mutant AG601, each grown with and without added
      formate. We used a combination of transcriptomics and proteomics to understand
      the physiological impact of the metabolic engineering, evolution, and medium
      supplementation. Medium supplementation with formate improved growth in both
      AG553 and AG601. Expression of C1 metabolism genes varied with formate addition,
      supporting the hypothesis that the primary benefit of added formate is the supply
      of C1 units for biosynthesis. Expression of stress response genes such as those
      involved in the sporulation cascade was dramatically over-represented in AG553,
      even after the addition of formate, suggesting that the source of the stress may
      be other issues such as redox imbalances. The sporulation response is absent in
      evolved strain AG601, suggesting that sporulation limits the growth of engineered
      strain AG553. A better understanding of the stress response and mechanisms of
      improved growth hold promise for informing rational improvement of C.
      thermocellum for lignocellulosic biofuel production.

PMID- 30187246
TI  - Determination of Azole Resistance and TR34/L98H Mutations in Isolates of
      Aspergillus Section Fumigati from Turkish Cystic Fibrosis Patients.
AB  - BACKGROUND: Aspergillus fumigatus is the species section Fumigati most frequently
      isolated from the respiratory tract of cystic fibrosis (CF) patients. Recent
      studies suggest that mutations in the Cyp51 gene, particularly TR34/L98H, are
      responsible for azole resistance. OBJECTIVES AND METHODS: The focus of this study
      was on section Fumigati isolates isolated from the respiratory tract samples of
      CF patients. More specifically, the goal was to detect A. fumigatus isolates,
      test their antifungal susceptibility to itraconazole, voriconazole and
      posaconazole, and finally determine the presence of TR34/L98H and other mutations
      in the isolates Cyp51A gene. RESULTS AND CONCLUSIONS: A set of 31 isolates of
      Aspergillus section Fumigati were obtained from the sputum samples of 6 CF
      patients and subsequently identified to species level by microsatellite
      genotyping. All isolates were determined as A. fumigatus and involved 14
      different genotypes. The minimal inhibitory concentrations to the three azoles
      were determined by the E-test method, and the Cyp51A gene was sequenced. One of
      the genotypes was found to be resistant to all azoles but no mutations were
      detected in the Cyp51A gene, especially the TR34/L98H mutation. Therefore,
      mutations in genes other than Cyp51A or other distinct mechanisms may be
      responsible for this reported multiazole resistance found in a Turkish CF
      patient.

PMID- 30187249
TI  - Correction to: Iatrogenic atrial septal defect: reassurance or inquisitiveness.
AB  - The original version of this article unfortunately contained a mistake. The
      presentation of reference 1 was incorrect. The correct information is given
      below.

PMID- 30187248
TI  - Improving timelines in reporting results from positive blood cultures: simulation
      of impact of rapid identification on therapy on a real-life cohort.
AB  - For patients with bloodstream infections, rapid initiation of the appropriate
      antimicrobial therapy is essential in reducing mortality and morbidity. New
      developments and automation in clinical microbiology labs speed up the
      identification and susceptibility results but are expensive. To gain insight in
      the added value of the new workflows, we simulated the possible impact of rapid
      identification and susceptibility tests on a real-life cohort of 158 positive
      blood culture episodes. Our routine workflow was theoretically challenged against
      two new workflows, one based on rapid identification with MALDI-TOF MS and one
      based on molecular testing. First, we observed an important role of the rapid
      communication of the gram stain results, as about one third of patients needed an
      adaptation of the antimicrobial therapy based on these results. Antibiotic
      adaptation based on the microorganism identification was necessary in 10% and in
      another 25% of cases after the availability of the susceptibility results. The
      added value of the newer workflow methods lies mainly in the field of the rapid
      identification and was rather limited in our cohort. In conclusion, for
      optimizing the blood culture workflow, each microbiology lab should critically
      scan its own workflow and know its own blood culture epidemiology, before
      investing in expensive or time-consuming processes.

PMID- 30187247
TI  - Viral infection and atherosclerosis.
AB  - Several risk factors have been described for the pathogenesis of atherosclerosis.
      Infectious diseases are suggested to be a causative factor, and some viruses have
      been studied for their relation with atherosclerotic diseases. Studies report two
      hypotheses, direct and indirect effects, for the role of viral infections in
      atherogenesis. Viruses are able to initiate atherosclerosis by two different
      pathways. They can exert their direct effects on atherogenesis by infecting
      vascular cells and then inducing inflammation in the endothelium and smooth
      muscle cells. Alternatively, they can also apply indirect effects by infecting
      non-vascular cells and inducing systemic inflammation. In this review, we
      consider the available data about the effects and correlations of DNA and RNA
      viruses on atherosclerosis.

PMID- 30187250
TI  - Eligibility of cardiac resynchronization therapy patients for subcutaneous
      implantable cardioverter defibrillators.
AB  - BACKGROUND: Before subcutaneous implantable cardioverter defibrillator (S-ICD)
      implantation, the adequacy of sensing is required to be verified through surface
      ECG screening. Our objective was to determine whether S-ICD can be considered as
      a supplementary therapy in patients who are receiving biventricular (BIV) pacing.
      METHODS: We evaluated 48 patients with BIV devices to determine S-ICD candidacy
      during BIV, left ventricular (LV), right ventricular (RV) pacing, and intrinsic
      conduction (left bundle branch block-LBBB) by using an automated screening tool.
      Eligibility was defined by the presence of at least one appropriate vector in the
      supine and standing positions. RESULTS: Eligibility was verified during BIV
      pacing in 34 (71%) patients. In patients screened-out, QRS duration was longer (p
      = 0.035) and ischemic cardiomyopathy was more frequent (p = 0.027). LV-only
      pacing was associated with a lower passing rate (46%) (p < 0.001 versus BIV). The
      LBBB QRS morphology during inhibited ventricular pacing was acceptable in 51% of
      patients. The QRS generated by RV pacing was acceptable in 25% of patients. In
      patients who passed the screening test during BIV, the QRS was not acceptable in
      76% during RV pacing (i.e., accidental loss of LV capture). The concomitant
      adequacy during inhibited ventricular pacing (i.e., possible intrinsic
      conduction) was not assessed in 40% of patients. CONCLUSIONS: S-ICD may be a
      supplemental therapy in the majority of CRT patients. Standard BIV pacing should
      be preferred to the LV-only pacing mode, as it is more frequently associated with
      adequacy of S-ICD sensing. Spontaneous LBBB and RV-paced QRS morphologies are
      frequently inadequate. Therefore, in patients selected for concomitant S-ICD and
      CRT implantation, accidental loss of LV capture or possible intrinsic conduction
      must be prevented.

PMID- 30187251
TI  - When is it too expensive? Cost-effectiveness thresholds and health care decision
      making.

PMID- 30187252
TI  - The impact of long-term care on primary care doctor consultations for people over
      75 years.
AB  - Many countries are adopting policies to create greater coordination and
      integration between acute and long-term care services. This policy is predicated
      on the assumption that these service areas have interdependent outcomes for
      patients. In this paper, we study the interdependencies between the long-term
      (home care) services and consultations with a primary care doctor, as used by
      people over 75 years. Starting with a model of individual's demand for doctor
      consultations, given supply, we formalize the hypothesis that exogenous increases
      to home care supply will reduce the number of consultations where these services
      are technical substitutes. Furthermore, greater coordination of public service
      planning and use of pooled budgets could lead to better outcomes because planners
      can account for these externalities. We test our main hypothesis using data from
      the British Household Panel Study for 1991-2009. To address potential concerns
      about endogeneity, we use a set of instrumental variables for home care motivated
      by institutional features of the social care system. We find that there is a
      statistically significant substitution effect between home care and doctor
      visits, which is robust across a range of specifications. This result has
      implications for policies that consider increased coordination between health
      care and social care systems.

PMID- 30187253
TI  - ?

PMID- 30187254
TI  - Adding the T to ADME: Predictive Toxicity in Renal Drug Development.

PMID- 30187256
TI  - Immediate implant placement following 1-year treatment with oral versus
      intravenous bisphosphonates: a histomorphometric canine study on peri-implant
      bone.
AB  - OBJECTIVES: Bisphosphonates (BPs) are anti-resorptive medications with inhibitory
      effects on osteoclasts which decrease bone turnover. The present study aimed to
      assess the early effects of BPs on peri-implant bone. MATERIALS AND METHODS:
      Twelve female mongrel dogs were assigned to one control and two experimental
      groups as follows: 12 months of oral alendronate (ALN, 3.5 mg/kg/week) or
      intravenous (IV) pamidronate (PAM, 1 mg/kg/week) for experimental groups.
      Following 8 weeks after implant insertion, the specimens were sacrificed,
      histological evaluation was performed, and C-terminal telopeptide of collagen I
      (CTx) analysis was performed on serums. RESULTS: PAM demonstrated the greatest
      marginal bone level (MBL), 2.64 +/- 0.48, followed by ALN and control, 2.5 +/-
      0.4 and 0.66 +/- 0.5 respectively. The least bone-implant contact was observed in
      PAM group (%39 +/- 0.03) while it was significantly greater in the control group
      (p < 0.05). PAM and ALN demonstrated < 10 CTx levels versus > 300 in controls.
      CONCLUSION: It is assumed that long-term oral or IV BP therapy decreases marginal
      bone resorption and osseointegration. These changes were more accentuated in IV
      BP administration. CTx does not seem to be a precise predictor for bisphosphonate
      related osteonecrosis of the jaw. CLINICAL RELEVANCE: BPs impair peri-implant
      bone remodeling and this phenomena may be effective for reducing resorption at
      esthetic zone implants; however, decrease in osseointegration may be a concern
      for implant treatment in patients receiving BPs.

PMID- 30187257
TI  - Stress-related hormones in association with periodontal condition in adolescents
      results of the epidemiologic LIFE Child study.
AB  - OBJECTIVES: The aim of this study was to investigate the associations between
      blood levels of stress-related hormones and early signs of periodontal disease in
      children and adolescents. MATERIALS AND METHODS: Within the LIFE (Leipzig
      research center for civilization diseases) Child study, 498 adolescents (10 to 18
      years) were included. Early signs of periodontal inflammation were measured by
      probing depth (PD) at six index teeth (16, 11, 26, 36, 31, 46). Blood levels of
      stress-related hormones (cortisol, dehydroepiandosterone-sulfate [DHEA-S]) and,
      additionally interleukine-6 (IL-6) were measured. Socioeconomic status, oral
      hygiene, orthodontic appliances, and nutritional status, recorded by body-mass
      index-standard-deviation-score (BMI-SDS), were considered as confounding factors.
      Additionally, in 98 participants, an oral chairside active matrix
      metalloproteinase-8 (aMMP-8) test was performed. Statistical tests are the Mann
      Whitney U tests, chi-squared tests and multivariate logistic regression model.
      RESULTS: IL-6, BMI-SDS as well as positive aMMP-8 test result were significantly
      associated with maximum PD > 3 mm (p < 0.05). However, no statistically
      significant associations between stress-related hormones (cortisol and DHEA-S)
      and presence of maximum PD > 3 mm were found (p > 0.05). Higher DHEA-S and BMI
      were associated with positive aMMP-8 result, even after adjusting for age and
      gender (p = 0.027, padj = 0.026). CONCLUSION: The results reveal no associations
      between PD and stress-related hormones cortisol and DHEA-S. aMMP-8 test result
      might be associated with DHEA-S level. Nutritional status seems to influence
      periodontal disease in adolescents. CLINICAL RELEVANCE: DHEA-S and BMI-SDS show
      associations with early signs of periodontal disease in adolescents aged 10 to 18
      years. This association should be confirmed by the investigation of high-risk
      groups.

PMID- 30187258
TI  - A Culturally Sensitive Approach to the Relationships between Identity Formation
      and Religious Beliefs in Youth.
AB  - Youth encounter issues of religion in the process of identity formation. However,
      most prior studies have focused on Christian youth in Western counties. This
      study examined the relationship between identity formation and religious beliefs
      in the Eastern national context where Buddhism and non-institutional folk
      religions are prevalent. Participants were 969 Japanese youth (51.3% female; Mage
      = 20.1). Both literal and symbolic religious beliefs were included and both a
      variable- and person-oriented approach were used based on the three-factor
      identity model. The results from the variable-oriented approach (i.e., identity
      processes) demonstrated that identity commitment was positively associated with
      literal religious beliefs, whereas reconsideration of commitment was positively
      associated with both literal and symbolic religious beliefs. Findings from the
      person-oriented approach (i.e., identity statuses) confirmed these results.
      Overall, this study highlights the importance of religious beliefs in the process
      of identity formation among youth in an Eastern national context.

PMID- 30187259
TI  - Clinicopathologic characteristics of non-small cell lung cancer in patients with
      smoking-related chronic obstructive pulmonary disease.
AB  - BACKGROUND: The purpose of this study was to clarify the clinicopathologic
      characteristics of non-small cell lung cancer (NSCLC) patients with smoking
      related chronic obstructive pulmonary disease (COPD) and to evaluate the
      biological behavior of this disease. We investigated the association between
      smoking-related COPD, the recurrence-free proportion (RFP) and the
      clinicopathological features of clinical stage I NSCLC patients. METHODS: Between
      2005 and 2014, 218 consecutive patients with clinical stage I NSCLC underwent
      complete resection with lobectomy or greater and systematic lymph node
      dissection. Differences in categorical outcomes were evaluated by the chi2 test.
      RFPs were estimated using the Kaplan-Meier method, and differences were evaluated
      using the log-rank test. RESULTS: The 5-year RFP of clinical stage I NSCLC
      patients with smoking-related COPD was 55%, which was significantly lower than in
      those without smoking-related COPD (85%; p < 0.001). Postoperative pathological
      factors, including moderate or poor histological differentiation, intratumoral
      vascular invasion and lymph node metastasis, were detected more often in patients
      with smoking-related COPD. In adenocarcinoma patients, the 5-year RFP of patients
      with smoking-related COPD was 47%, which was significantly lower than in those
      without smoking-related COPD (87%; p < 0.001). The presence of a solid component
      was more frequently found in patients with smoking-related COPD (p = 0.007).
      CONCLUSION: Clinical stage I NSCLC patients with smoking-related COPD have
      histologically more invasive tumors than those without smoking-related COPD.

PMID- 30187255
TI  - Time course of liver mitochondrial function and intrinsic changes in oxidative
      phosphorylation in a rat model of sepsis.
AB  - BACKGROUND: Tissue ATP depletion and oxidative stress have been associated with
      the severe outcomes of septic shock. One of the compensatory mechanisms to
      alleviate the sepsis-induced mitochondrial dysfunction could be the increase in
      oxidative phosphorylation efficiency (ATP/O). We propose to study liver
      mitochondrial function and oxidative stress and the regulatory mechanism of
      mitochondrial oxidative phosphorylation efficiency in an animal model of sepsis.
      METHODS: We induced sepsis in rats by cecal ligation and perforation (CLP). Six,
      24, or 36 h following CLP, we measured liver mitochondrial respiration,
      cytochrome c oxidase activity, and membrane permeability. We determine oxidative
      phosphorylation efficiency, by measuring ATP synthesis related to oxygen
      consumption at various exogenous ADP concentrations. Finally, we measured radical
      oxygen species (ROS) generation by liver mitochondria and mRNA concentrations of
      UCP2, biogenesis factors, and cytokines at the same end points. RESULTS: CLP rats
      presented hypotension, lactic acidosis, liver cytolysis, and upregulation of
      proinflammatory cytokines mRNA as compared to controls. Liver mitochondria showed
      a decrease in ATP synthesis and oxygen consumption at 24 h following CLP. A
      marked uncoupling of oxidative phosphorylation appeared 36 h following CLP and
      was associated with a decrease in cytochrome c oxidase activity and content and
      ATP synthase subunit beta content (slip mechanism) and an increase in
      mitochondrial oligomycin-insensitive respiration, but no change in mitochondrial
      inner membrane permeability (no leak). Upregulation of UCP2 mRNA resulted in a
      decrease in mitochondrial ROS generation 24 h after the onset of CLP, whereas ROS
      over-generation associated with slip at cytochrome c oxidase observed at 36 h was
      concomitant with a decrease in UCP2 mRNA expression. CONCLUSIONS: Despite a
      compensatory increase in mitochondrial biogenesis factors, liver mitochondrial
      functions remain altered after CLP. This suggests that the functional
      compensatory mechanisms reported in the present study (slip at cytochrome c
      oxidase and biogenesis factors) were not strong enough to increase oxidative
      phosphorylation efficiency and failed to limit liver mitochondrial ROS over
      generation. These data suggest that treatments based on cytochrome c infusion
      could have a role in mitochondrial dysfunction and/or ROS generation associated
      with sepsis.

PMID- 30187260
TI  - Differential selective hypothermic intercostal artery perfusion: a new method to
      probe spinal cord perfusion during thoracoabdominal aortic aneurysm repair.
AB  - OBJECTIVE: To prevent paraplegia in patients undergoing thoracoabdominal aortic
      aneurysm repair, the importance of preoperative identification of the Adamkiewicz
      artery and reconstruction of critical intercostal artery have been advocated.
      Conversely, significance of collateral network for spinal cord perfusion has been
      recognized. We invented a new system consisting of a direct monitoring of
      cerebrospinal fluid temperature (CSFT) and differential selective hypothermic
      intercostal artery perfusion (D-HIAP). METHODS: After exposing a critical
      intercostal artery, a 10-mm prosthetic graft was anastomosed in an end to side
      fashion. A balloon-tipped catheter was inserted into the graft to perfuse with 15
      degrees C blood. Neighboring intercostal arteries were also perfused in the same
      fashion. Serial monitoring of CSFT was performed. Between January 2011 and
      January 2015, D-HIAP was employed in 50 patients with Adamkiewicz artery that
      located within a reconstructed area. RESULTS: Significant CSFT drop was recorded
      after initiation of D-HIAP in 42 (84%) patients. Of those, 34 (68%) patients
      showed significantly lowered CSFT with D-HIAP into a single critical intercostal
      artery. Perfusion into plural intercostal arteries was necessary for CSFT drop in
      2 cases (4%), and plural intercostal artery perfusion further enhanced CSFT drop
      that had been modestly achieved by single intercostal artery perfusion in 6 cases
      (12%). Eight (16%) patients did not exhibit a significant drop in CSFT even when
      D-HIAP was employed for the critical and neighboring intercostal arteries.
      CONCLUSIONS: The detection of a disparity in temperature between the intrathecal
      space and blood generated by D-HIAP revealed individual variability in CSFT
      changes, which may imply a complexity in spinal cord perfusion. Intraoperative D
      HIAP may help to identify a major blood supply for spinal cord perfusion and
      underlying collateral network.

PMID- 30187261
TI  - Allopregnanolone and Progesterone in Experimental Neuropathic Pain: Former and
      New Insights with a Translational Perspective.
AB  - In the last decades, an active and stimulating area of research has been devoted
      to explore the role of neuroactive steroids in pain modulation. Despite
      challenges, these studies have clearly contributed to unravel the multiple and
      complex actions and potential mechanisms underlying steroid effects in several
      experimental conditions that mimic human chronic pain states. Based on the
      available data, this review focuses mainly on progesterone and its reduced
      derivative allopregnanolone (also called 3alpha,5alpha-tetrahydroprogesterone)
      which have been shown to prevent or even reverse the complex maladaptive changes
      and pain behaviors that arise in the nervous system after injury or disease.
      Because the characterization of new related molecules with improved specificity
      and enhanced pharmacological profiles may represent a crucial step to develop
      more efficient steroid-based therapies, we have also discussed the potential of
      novel synthetic analogs of allopregnanolone as valuable molecules for the
      treatment of neuropathic pain.

PMID- 30187262
TI  - Methods of space maintenance for premature loss of a primary molar: a review.
AB  - AIM: This critical appraisal attempts to answer the question: What is the best
      method of space maintenance (SM) following premature loss of a primary molar in
      children under 12 years old? METHODS: A search to identify studies relevant to
      the PICO was conducted. Single case reports and studies prior to 1986 were
      excluded. The principles of GRADE were followed to appraise the evidence.
      RESULTS: 20 studies were identified, which evaluated 2265 space maintainers
      (SMs). Two studies were graded high quality, four moderate, eight low, and six
      very low. All studies reported on longevity outcomes and most on adverse effects.
      CONCLUSIONS: There was no strong evidence favouring a particular SM, the
      following recommendations were made: (a) strong recommendations: In cases where
      rubber dam cannot be used clinicians should not use Glass Fibre Reinforced
      Composite Resin (GFRCR) SMs. (b) Weak recommendations: Crown and Loop SMs are
      recommended for loss of primary first molars; GFRCR SMs (placed under rubber dam)
      are recommended for loss of primary second molars. Bilateral SMs may have
      questionable efficacy and their use where there is loss of multiple molars in the
      same quadrant should be weighed against the risk of unwanted tooth movements,
      loss of a removable SM or no space maintenance at all.

PMID- 30187263
TI  - Relative effectiveness of direct and indirect pulp capping in the primary
      dentition.
AB  - INTRODUCTION: Carious or traumatised teeth with a normal pulp status or with
      reversible pulpitis need an indirect or direct pulp capping procedure to keep the
      pulp vital. AIM: To evaluate the clinical outcome of both interventions for
      treating vital primary teeth. STUDY DESIGN: Two reviewers on Pubmed and ISI Web
      of Science performed a comprehensive literature review of publications from 1966
      until December 2017. Among PubMed abstracts, publications were selected according
      to the following criteria: prospective clinical study, correct indication for the
      performed treatment, and clear definition of clinical and/or radiographic success
      criteria. The strict selection criteria limited the amount of randomised
      controlled trials (RCT) or controlled clinical trials (CT); especially for
      "indirect pulp therapy", "direct pulp capping" and the number of RCTs was
      limited. CONCLUSIONS: Based on a systematic review (20 controlled clinical
      studies or randomised controlled clinical studies), the following statements can
      be given: Due to the opportunity of tissue repair, indirect pulp treatment can be
      an acceptable procedure for reversible pulp inflammation. The use of adhesives
      for indirect pulp capping in a single-visit procedure after gentle caries removal
      can be recommended. Successful pulp capping is possible under defined conditions
      (symptom-free tooth, disinfection of pulp exposures, Class-I cavity) and
      appropriate sealing of the cavity with an effective dentine seal being a conditio
      sine qua non. There is maximum evidence for the use of disinfecting solutions
      prior to pulp capping and Dycal as pulp capping material. Longer follow-up
      periods, more clinical studies, comparable conditions, and clear definitions of
      evaluation criteria are needed to confirm the results of endodontic treatment in
      primary teeth.

PMID- 30187264
TI  - User Acceptability of Whole Exome Reproductive Carrier Testing for Consanguineous
      Couples in Australia.
AB  - The study aimed to explore with consanguineous couples in Australia the
      acceptability and perceived utility of whole exome reproductive carrier screening
      for autosomal recessive and X-linked recessive conditions. Semi-structured
      interviews with 21 consanguineous couples were conducted prior to the offer of
      screening. Interviews were coded, and thematic analysis was informed by an
      inductive approach. Three major themes were identified: experiences and attitudes
      of Australian consanguineous couples, childhood genetic conditions and beliefs,
      and the perceived utility of genomic screening. All but one couple had previously
      sought genetic advice, and a large majority of couples were aware of childhood
      conditions within their family or community. Thirteen couples perceived
      consanguinity as increasing the risk of having affected children. Nine spoke of
      premarital screening programs routinely conducted in their countries of origin.
      All supported the concept and availability of genomic reproductive carrier
      screening. Hypothetically, if found to be carriers of a severe childhood
      disorder, 13 couples reported they would test a pregnancy, and 12 of whom would
      consider termination of pregnancy or pre-implantation genetic diagnosis. Four
      couples would not test a pregnancy and two were unsure. A majority of couples
      would communicate potential at-risk status to family members, although there were
      some caveats. Fourteen couples chose to have exome screening and reported that
      they would utilize the results with the goal of preventing childhood conditions.
      Of these couples, nine (64%) had an affected child but were aware that testing
      may reveal they were at risk for a child with a different condition and five
      (71%) without an affected child. While from diverse ethnic and backgrounds, all
      couples practiced a religion and all but one couple were recruited from the same
      clinical genetics unit, with a likely higher genetic literacy and bias towards
      accepting genetic testing. However, the choice made by all couples was reportedly
      made with consideration of their personal values, their current family situation,
      and exome testing issues, including fear of incidental findings and concerns
      about test reliability.

PMID- 30187266
TI  - Breast implant-associated anaplastic large cell lymphoma: a pictorial review.
AB  - Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a newly
      described and rare T-cell lymphoma of the breast. Since 2007, there have been 56
      cases of confirmed BIA-ALCL in Australia and New Zealand. The incidence is
      believed to be on the rise as the prevalence of elective breast implantation
      increases. In 2016, the World Health Organization (WHO) classified BIA-ALCL as a
      recognised entity and emphasised the importance of surgical management of the
      disease. BIA-ALCL typically presents as a delayed, non-infective fluid collection
      around a textured breast implant or residual fibrous scar capsule. The mean age
      of presentation is 47 years, with an average time frame of 7.5 years following
      breast implantation. Although rare, BIA-ALCL is increasing in incidence. To avoid
      delays in diagnosis, radiologists should consider this form of lymphoma in the
      differential of any non-acute peri- or post-prosthetic effusion, and suggest
      cytological evaluation, so as not to miss this rare but important diagnosis.
      TEACHING POINTS: * BIA-ALCL is a newly described and rare T-cell lymphoma of the
      breast. * Since 2007, there have been 56 cases of confirmed BIA-ALCL in Australia
      and New Zealand. * BIA-ALCL presents as a delayed, non-infective fluid
      collection. * The effusion typically accumulates around a textured breast implant
      or residual fibrous capsule.

PMID- 30187267
TI  - Spectrum of gastrointestinal lesions of neurofibromatosis type 1: a pictorial
      review.
AB  - Neurofibromatosis type 1 (NF1) is one of the most common genetic disorders.
      Gastrointestinal manifestations of NF-1 are seldom thought of in routine clinical
      practice and might thus be significantly under-recognised. Their heterogeneous
      spectrum ranges from localised microscopic proliferative lesions to grossly
      recognizable mass-forming neurofibromas, neuroendocrine and gastrointestinal
      stromal tumours (GIST). The aim of this study is discussing the imaging
      evaluation and characterisation of the abdomen lesions in patients with NF1.
      TEACHING POINTS: * Neurofibromatosis type (NF-1) is one of the most common single
      gene disorders. * Every organ system can be involved and intra-abdominal
      manifestations are underestimated. * The NF1 abdominal manifestations comprehend
      five categories of tumours. * Neurogenic tumours including with neurofibromas are
      the most common type. * Early diagnosis of abdominal manifestations of NF-1 based
      on imaging patterns is necessary for appropriate treatment to avoid serious
      organic complications related to tumour mass.

PMID- 30187265
TI  - Imaging in Lyme neuroborreliosis.
AB  - Lyme neuroborreliosis (LNB) is a tick-borne spirochetal infection with a broad
      spectrum of imaging pathology. For individuals who live in or have travelled to
      areas where ticks reside, LNB should be considered among differential diagnoses
      when clinical manifestations from the nervous system occur. Radiculitis,
      meningitis and facial palsy are commonly encountered, while peripheral
      neuropathy, myelitis, meningoencephalitis and cerebral vasculitis are rarer
      manifestations of LNB. Cerebrospinal fluid (CSF) analysis and serology are key
      investigations in patient workup. The primary role of imaging is to rule out
      other reasons for the neurological symptoms. It is therefore important to know
      the diversity of possible imaging findings from the infection itself. There may
      be no imaging abnormality, or findings suggestive of neuritis, meningitis,
      myelitis, encephalitis or vasculitis. White matter lesions are not a prominent
      feature of LNB. Insight into LNB clinical presentation, laboratory test methods
      and spectrum of imaging pathology will aid in the multidisciplinary interaction
      that often is imperative to achieve an efficient patient workup and arrive at a
      correct diagnosis. This article can educate those engaged in imaging of the
      nervous system and serve as a comprehensive tool in clinical cases. KEY POINTS: *
      Diagnostic criteria for LNB emphasise exclusion of an alternative cause to the
      clinical symptoms. * MRI makes a crucial contribution in the diagnosis and follow
      up of LNB. * MRI may have normal findings, or show neuritis, meningitis,
      myelitis, encephalitis or vasculitis. * White matter lesions are not a prominent
      feature of LNB.

PMID- 30187268
TI  - The ESR Audit Tool (Esperanto): genesis, contents and pilot.
AB  - Clinical audit is a powerful tool to improve patient care, experience and
      outcome. It consists of measuring a clinical outcome or procedure against
      predefined standards, identifying differences between current practice and the
      standards, and changing practice where necessary to facilitate meeting the
      standards, followed by re-audit (the audit cycle). The recently implemented
      European Council Basic Safety & Standards (BSS) Directive (2013/59/Euratom)
      emphasises that carrying out clinical audit is compulsory in the EU "in
      accordance with national requirements". In 2017, the ESR published a Clinical
      Audit Tool booklet (Esperanto), consisting of an explanation of clinical audit,
      guidance on how to start a program in a radiology department, and 17 sample audit
      templates which could guide departments through the process of performing audits.
      A sample of key audits from these templates was performed by participating
      EuroSafe Imaging Star departments as a pilot project, with participants providing
      feedback on the audit process, and their experience of using the templates.
      Responses showed that the chosen topics were relevant, the audit process and
      templates were straightforward and easy to use, and that the audit process was
      time-efficient. Following this successful pilot, the Audit Tool has been made
      available for all potential users through the ESR website. KEY POINTS: * Clinical
      audit is the process of assessing one's practice against defined standards,
      altering practice if necessary to meet standards, and re-assessing following
      changes to confirm improvement * Clinical audit should be part of practice in all
      radiology departments * Under European Council Directive 2013/59/Euratom,
      clinical audit is compulsory in the EU "in accordance with national requirements"
      * The ESR has developed a Clinical Audit Tool (Esperanto) to explain the process
      and guide departments through sample audit templates * This Clinical Audit Tool
      was successfully piloted in 2017, and is now available to all users on the ESR
      website.

PMID- 30187269
TI  - Radiology trainees forum survey report on workplace satisfaction, ESR education,
      mobility and stress level.
AB  - OBJECTIVES: The Radiology Trainees Forum (RTF) of the European Society of
      Radiology (ESR) conducted a survey among radiologists in training to gather and
      evaluate data on workplace satisfaction, ESR educational initiatives, mobility of
      professionals and stress levels. METHODS: A questionnaire was forwarded to
      radiologists in training across Europe. The subject of the questionnaire was
      related to: (1) the working place, (2) safety of the working environment, (3)
      satisfaction at the working place, (4) familiarity with educational initiatives
      within the ESR and (5) reasons and motivation for mobility. Results were obtained
      and analysed. RESULTS: Invitations to participate were sent by the ESR office to
      radiologists in training across Europe. A total of 1045 radiologists responded to
      the questionnaire; 77.8% were trainees and 22.2% were certified radiologists. Of
      the responders 65.3% considered the working place safe. Only 25.7% considered
      themselves involved in management, 43.9% would consider working in another
      country, and 52.3% were moderately satisfied with their working place. Of the
      responders 46.8% did not have any teaching responsibilities; 59.7% knew the
      European Diploma in Radiology (EDiR) and 69.7% were not aware of the content of
      the ESR European Training Curriculum (ETC). CONCLUSION: The level of training in
      aspects related to management safety and quality is low among trainees. The level
      of satisfaction at work is adequate but not sufficient. The degree of
      responsibility in training tasks is scarce. A small percentage is familiar with
      the ESR educational initiatives. As for the mobility the main reservation is lack
      of confidence in the training acquired. MAIN MESSAGES: * For satisfaction levels
      to improve, it is vital to include more creative aspects of the profession, such
      as research and teaching, in balance with the routine aspects of radiology. *
      Furthermore, a greater involvement of radiologists in patient care is also
      essential in radiology training. * To facilitate mobility, it is important to
      standardise training across European countries through universal programmes and
      training controls such as the EDiR and the ETC.

PMID- 30187272
TI  - Effect of a 6-week supervised detraining period on bone metabolism markers and
      their association with ergometrics and components of the hypothalamic-pituitary
      gonadal (HPG) axis in professional male soccer players.
AB  - The aim of this study was to examine the effect of a supervised 6-week detraining
      period on bone metabolism markers, and their association with ergometrics, and
      components of the hypothalamic-pituitary-gonadal (HPG) axis in elite male
      professional soccer players. Sixty-seven soccer players (mean age +/- SD 23.4 +/-
      5.2 years) that were following a supervised training program participated in this
      study. Players were tested twice: immediately after the conclusion of the
      competition period, and following the detraining period, for the determination of
      bone-turnover rates, ergometrics, and components of the HPG-axis. The detraining
      period resulted in significant reduction in osteocalcin [OC] (p < 0.001), C
      terminal propeptide of collagen type-I [CICP] (p = 0.002), and bone-alkaline
      phosphatase [b-ALP] (p < 0.001) values, while C-terminal telopeptide [CTX] was
      increased (p < 0.001). No significant relationships were apparent between bone
      biomarkers and body weight, body-fat %, total testosterone, free testosterone,
      estradiol, follicle-stimulating hormone, and luteinizing hormone in both
      experimental sessions (p > 0.05). Similarly, despite the deterioration in
      ergometrics after detraining (all p < 0.001), no significant correlations were
      evident (p > 0.05) between bone biomarkers and maximal oxygen consumption, squat
      jump, countermovement jump, and 20 m sprint performance, and also between %
      change of bone biomarkers and ergometrics, apart from a weak relationship (p =
      0.041) between OC and VO2max of questionable value. Our results suggest that the
      6-week soccer off-season detraining period in our study negatively affected bone
      physiology as reflected by the suppression of bone-formation rate and a parallel
      induction of bone resorption. The cause of this acute alteration of bone-turnover
      rates is not related to the examined components of the HPG-axis, although
      parallels is not associated with the changes in ergometrics.

PMID- 30187270
TI  - High-flow nasal oxygen versus noninvasive ventilation in adult patients with
      cystic fibrosis: a randomized crossover physiological study.
AB  - BACKGROUND: Noninvasive ventilation (NIV) is the first-line treatment of adult
      patients with exacerbations of cystic fibrosis (CF). High-flow nasal oxygen
      therapy (HFNT) might benefit patients with hypoxemia and can reduce physiological
      dead space. We hypothesized that HFNT and NIV would similarly reduce work of
      breathing and improving breathing pattern in CF patients. Our objective was to
      compare the effects of HFNT versus NIV in terms of work of breathing, assessed
      noninvasively by the thickening fraction of the diaphragm (TFdi, measured with
      ultrasound), breathing pattern, transcutaneous CO2 (PtcCO2), hemodynamics,
      dyspnea and comfort. METHODS: Adult CF patients who had been stabilized after
      requiring ventilatory support for a few days were enrolled and ventilated with
      HFNT and NIV for 30 min in crossover random order. RESULTS: Fifteen patients were
      enrolled. Compared to baseline, HFNT, but not NIV, reduced respiratory rate (by 3
      breaths/min, p = 0.01) and minute ventilation (by 2 L/min, p = 0.01). Patients
      also took slightly larger tidal volumes with HFNT compared to NIV (p = 0.02).
      TFdi per breath was similar under the two techniques and did not change from
      baseline. MAP increased from baseline with NIV and compared to HFNT (p <= 0.01).
      Comfort was poorer with the application of both HFNT and NIV than baseline. No
      differences were found for heart rate, SpO2, PtcCO2 or dyspnea. CONCLUSIONS: In
      adult CF patients stabilized after indication for ventilatory support, HFNT and
      NIV have similar effects on diaphragmatic work per breath, but high-flow therapy
      confers additional physiological benefits by decreasing respiratory rate and
      minute ventilation. CLINICAL TRIAL REGISTRATION: Ethics Committee of St.
      Michael's Hospital (REB #14-338) and clinicaltrial.gov (NCT02262871).

PMID- 30187271
TI  - Membranotropic effects of omega-hydroxypalmitic acid and Ca2+ on rat liver
      mitochondria and lecithin liposomes. Aggregation and membrane permeabilization.
AB  - The paper examines membranotropic Ca2+-dependent effects of omega-hydroxypalmitic
      acid (HPA), a product of omega-oxidation of fatty acids, on the isolated rat
      liver mitochondria and artificial membrane systems (liposomes). It was
      established that in the presence of Ca2+, HPA induced aggregation of liver
      mitochondria, which was accompanied by the release of cytochrome c from the
      organelles. It was further demonstrated that the addition of Ca2+ to HPA
      containing liposomes induced their aggregation and/or fusion. Ca2+ also caused
      the release of the fluorescent dye sulforhodamine B from liposomes, indicating
      their permeabilization. HPA was shown to induce a high-amplitude swelling of Ca2+
      loaded mitochondria, to decrease their membrane potential, to induce the release
      of Ca2+ from the organelles and to result in the oxidation of the mitochondrial
      NAD(P)H pool. Those effects of HPA were not blocked by the MPT pore inhibitor
      CsA, but were suppressed by the mitochondrial calcium uniporter inhibitor
      ruthenium red. The effects of HPA were also observed when Ca2+ was replaced with
      Sr2+ (but not with Ba2+ or Mg2+). A supposition is made that HPA can induce a
      Ca2+-dependent aggregation of mitochondria, as well as Ca2+dependent CsA
      insensitive permeabilization of the inner mitochondrial membrane - with the
      subsequent lysis of the organelles.

PMID- 30187273
TI  - Denosumab is effective toward glucocorticoid-induced osteoporosis patients
      complicated with rheumatic diseases regardless of prior anti-osteoporotic drugs.
AB  - We examined the efficacy and safety of denosumab as treatment for glucocorticoid
      induced osteoporosis (GIOP) patients complicated with rheumatic diseases, by
      measuring patients' lumber bone mineral density (BMD) and bone turnover markers.
      A total of 66 consecutive patients for whom denosumab was initiated between July
      2013 and August 2016 were enrolled and evaluated for 12 months. All of the
      patients were treated with glucocorticoids for underlying rheumatic diseases. The
      clinical assessment included measurements of the BMD of the lumbar spine (L2-L4)
      by a dual-energy X-ray absorptiometry technique and the bone turnover markers N
      terminal telopeptide of type 1 collagen (NTX) in urine, serum intact procollagen
      type 1 N-terminal propeptide (P1NP), and bone-specific alkaline phosphatase (BAP)
      at baseline, 6 months and 12 months after the start of denosumab treatment.
      Adverse events (AEs) until 12 months were also analyzed. The mean percentage
      changes in BMD from baseline to 6 and 12 months were significant (2.85% increase,
      p < 0.0001 and 4.40% increase, p < 0.0001, respectively) regardless of the prior
      anti-osteoporotic drugs treatment (16 no transition from anti-osteoporotic drugs,
      27 transition from bisphosphonate, 23 transition from teriparatide). The
      decreases in NTX, P1NP and BAP at 6 and 12 months were also significant. No
      serious AEs were noted. A multivariable logistic analysis showed that the
      prednisolone dose at baseline was associated with the clinical response to
      denosumab. In a real-world setting, denosumab was effective and safe for treating
      GIOP patients complicated with rheumatic diseases regardless of prior anti
      osteoporotic drug treatment.

PMID- 30187274
TI  - Bone marrow lesion is associated with disability for activities of daily living
      in patients with early stage knee osteoarthritis.
AB  - Osteoarthritis of the knee (knee OA) induces pain, loss of mobility and
      diminished activities of daily living (ADL). Although an understanding of the
      pathophysiology of early stage knee OA has been developed, the structural changes
      associated with disability for ADL in early stage knee OA are still unclear. The
      aim of the present study was to examine magnetic resonance imaging (MRI)-detected
      changes associated with disability for ADL in patients with early stage knee OA.
      One hundred and thirty-two patients with early stage medial knee OA (Kellgren
      Lawrence grade <= 2) who first visited the outpatient clinic at our university
      hospital were included. They were also examined by 3.0-Tesla knee MRI. The OA
      associated structural changes were scored using the Whole-Organ Magnetic
      Resonance Imaging Score (WORMS), and clinical manifestations were evaluated by
      the Japanese Knee Osteoarthritis Measure (JKOM). Median quartile regression was
      used for the analysis. Cartilage lesion, subchondral bone attrition and
      osteophytes were observed in all patients. Bone marrow lesions (BMLs) and
      synovitis were observed in 60% and 55% of the patients, respectively. Subchondral
      cysts and ligament changes were observed in 6% and 17% of the patients,
      respectively. Pain severity of the patients was associated with medial cartilage
      lesions (coefficient 2.50, 95% confidence interval 0.61-4.40, p < 0.01).
      Disability for ADL of the patients was associated with BMLs in the medial side of
      the knee joint (0.82, 0.21-1.02, p = 0.04). BMLs in the medial side of the knee
      joint were associated with disability for ADL of patients with early stage medial
      knee OA.

PMID- 30187275
TI  - Development of scoliosis in young children with osteogenesis imperfecta
      undergoing intravenous bisphosphonate therapy.
AB  - The purpose of this study was to clarify the prevalence of scoliosis and
      determine risk factors for the development of scoliosis in young children with
      osteogenesis imperfecta (OI) who underwent intravenous pamidronate (PAM) therapy.
      Thirty-four young children with OI who had no scoliosis at the first PAM
      administration underwent cyclic PAM therapy alone. The medical records and
      radiographs of these patients were retrospectively reviewed. We examined the
      relationship between scoliosis (Cobb angle >= 10) and type of OI (Sillence
      classification: types I, III, and IV), physical mobility, Z-scores of bone
      mineral density in L2-4 of the lumbar spine (L2-4 BMD Z-scores), age of patients
      at first treatment with PAM, pelvic frontal tilt and leg-length discrepancy. The
      prevalence of scoliosis was 23.5% in 34 young children with OI who underwent PAM
      therapy for a mean of 4.2 years. Lower L2-4 BMD Z-scores, the presence of coronal
      and sagittal vertebral deformities and higher percentage of corrective osteotomy
      in the lower extremities were significant risk factors for the development of
      scoliosis. In patients with type III or IV OI, L2-4 BMD Z-scores were
      significantly lower (p = 0.02) and the percentage of patients who started PAM
      therapy in early childhood was significantly lower in scoliosis group than in the
      non-scoliosis group (p = 0.01). Development of scoliosis depends on the severity
      of OI and has a strong relationship with bone fragility even under PAM therapy.
      Starting intravenous PAM therapy in infancy or early childhood has a potential to
      prevent the occurrence and progression of scoliosis associated with bone
      fragility in young children with severe type III or IV OI.

PMID- 30187276
TI  - FGF2-responsive genes in human dental pulp cells assessed using a rat spinal cord
      injury model.
AB  - The central nervous system in adult mammals does not heal spontaneously after
      spinal cord injury (SCI). However, SCI treatment has been improved recently
      following the development of cell transplantation therapy. We recently reported
      that fibroblast growth factor (FGF) 2-pretreated human dental pulp cells (hDPCs)
      can improve recovery in a rat model of SCI. This study aimed to investigate
      mechanisms underlying the curative effect of SCI enhanced via FGF2 pretreatment;
      we selected three hDPC lines upon screening for the presence of mesenchymal stem
      cell markers and of their functionality in a rat model of SCI, as assessed using
      the Basso, Beattie, and Bresnahan score of locomotor functional scale,
      electrophysiological tests, and morphological analyses. We identified FGF2
      responsive genes via gene expression analyses in these lines. FGF2 treatment
      upregulated GABRB1, MMP1, and DRD2, which suggested to contribute to SCI or
      central the nervous system. In an expanded screening of additional lines, GABRB1
      displayed rather unique and interesting behavior; two lines with the lowest
      sensitivity of GABRB1 to FGF2 treatment displayed an extremely minor effect in
      the SCI model. These findings provide insights into the role of FGF2-responsive
      genes, especially GABRB1, in recovery from SCI, using hDPCs treated with FGF2.

PMID- 30187278
TI  - Natural Killer Cell IFNgamma Secretion is Profoundly Suppressed Following
      Colorectal Cancer Surgery.
AB  - BACKGROUND: Surgical stress results in a significant reduction in natural killer
      (NK) cell cytotoxicity (NKC), which has been linked to postoperative cancer
      metastases. However, few studies have measured the impact of surgical stress upon
      NK cell IFNgamma secretion (NKA), a cytokine with essential roles in controlling
      infection and metastases. The objective of this study was to investigate the
      impact of surgical stress on NKA in colorectal cancer (CRC) surgery patients.
      METHODS: Peripheral blood was collected from CRC surgery patients (n = 42)
      preoperatively and on postoperative day (POD) 1, 3, 5, 28, and 56. Healthy donor
      blood (n = 27) was collected for controls. We assessed NKA by production of
      IFNgamma following whole blood cytokine stimulation, NKC by 51Cr-release assay,
      and immune cell profiling by flow cytometry. RESULTS: The mean reduction in NKA
      on POD1 compared with baseline was 83.1% (standard deviation 25.2%; confidence
      interval 75-91), and therefore the study met the primary endpoint of
      demonstrating a > 75% decrease in a cohort of CRC surgery patients (p < 0.0001).
      The profound and universal suppression of NKA persisted with 65.5% (19/29) and
      33.3% (4/12) of patients with levels measuring < 75% of baseline on POD28 and
      POD56 respectively. The NKC was significantly reduced on POD1, but the degree was
      less pronounced (24.6%, p = 0.0024). Immune cell profiling did not reveal
      differences in the absolute number of NK cells (CD3-CD56+) or the ratio of
      CD56dim-to-CD56bright subsets. CONCLUSIONS: NKA is significantly suppressed for
      up to two months following surgery in CRC patients, a degree of surgery-induced
      immunosuppression far worse than previously reported.

PMID- 30187277
TI  - Umbilical cord mesenchymal stem cell conditioned medium restored the expression
      of collagen II and aggrecan in nucleus pulposus mesenchymal stem cells exposed to
      high glucose.
AB  - Diabetes can cause intervertebral disc degeneration by accelerating apoptosis and
      senescence of nucleus pulposus mesenchymal stem cells (NPMSCs). The aim of this
      study was to determine the effect of umbilical cord mesenchymal stem cells
      (UCMSCs) conditioned medium on high glucose (HG) induced degradation of NPMSCs
      produced extracellular matrix. NPMSCs were isolated from the inner intervertebral
      disc tissue using type XI collagenase digestion. According to Annexin V/propidium
      iodide (PI) flow cytometry analysis; HG leads to an increase in the rate of
      NPMSCs apoptosis. HG injury also resulted in a marked decrease in the percentage
      of cells in G0/G1 phase and an increase in cells in S and G2/M phases, indicating
      that HG induces cell cycle arrest of NPMSCs. Treatment with MSC-CM abolished the
      effect of HG on cell senescence. HG also significantly inhibited collagen II and
      aggrecan expression in NPMSCs. After MSC-CM treatment, the expression of these
      two extracellular matrix components was restored. Exposure to HG resulted in
      phosphorylation of p38 MAPK, while the levels of total p38 MAPK were not
      affected. When treated with MSC-CM, phosphorylated p38 MAPK levels of NPMSCs were
      lower than those without CM treatment. Our data also showed that p38 MAPK
      inhibitor SB203580 can attenuated phosphorylation of p38 MAPK and resumed the
      collagen II and aggrecan expression in NPMSCs. In summary, this study
      demonstrated that MSC-CM has the potential to alleviate HG induced extracellular
      matrix degradation via the p38 MAPK pathway.

PMID- 30187279
TI  - Quality Comes with the (Anatomic) Territory: Evaluating the Impact of Surgeon
      Operative Mix on Patient Outcomes After Pancreaticoduodenectomy.
AB  - BACKGROUND: Recent support for centralization of complex operations, such as
      pancreaticoduodenectomy (PD), is based on surgeon-specific volume-outcome
      relationships. This study examined whether volume of anatomically related
      operations (operative mix), besides PD, is also independently associated with
      postoperative outcomes after PD. METHODS: The study queried the Nationwide
      Inpatient Sample (2004-2009) for surgeons performing PD. Operative mix (OM) was
      defined as the year-specific number of other pancreatic, hepatic, biliary, and
      gastric operations performed by individual surgeons. Regression models included
      surgeon and hospital PD volume, adjusted for other hospital- and patient-specific
      factors. RESULTS: Among 1747 surgeons, 88.3% had low PD volume (<= 5 cases/year),
      8.9% had moderate PD volume (6-16 cases/year), and 2.8% had high PD volume (>= 17
      cases/year). Low-PD-volume surgeons with high OM (>= 21 cases/year) (4.4%),
      moderate-PD-volume surgeons with high OM (3.4%), and high-PD-volume surgeons with
      high OM (2.7%) each had lower mortality than low-PD-volume surgeons with low OM
      (9.3%; all p <= 0.02). The frequency of prolonged hospitalization among low
      PD/high-OM surgeons (45.3%) was lower than among low-PD/low-OM surgeons (61.6%; p
      < 0.001). Increasing OM volume was associated with decreased inpatient mortality,
      shorter hospital stay, and lower likelihood of any postoperative complication,
      using unadjusted regression (all p < 0.001). Adjusted regression results
      indicated that increasing OM volume is a significant predictor of decreased odds
      of a prolonged hospital stay (odds ratio [OR] 0.81; 95% confidence interval [CI]
      0.73-0.90; p < 0.001). CONCLUSIONS: Surgeon PD volume is an important predictor
      of outcomes after PD. However, surgeon OM volume identifies a subset of lower-PD
      volume surgeons with more favorable outcomes.

PMID- 30187280
TI  - ASO Author Reflections: Tumor Cell Content and RNA Integrity of Surgical Tissues
      from Different Types of Tumors and Its Correlation with Ex Vivo and In Vivo
      Ischemia.

PMID- 30187281
TI  - Controversies in Surgical Oncology: Does the Minimally Invasive Approach for
      Rectal Cancer Provide Equivalent Oncologic Outcomes Compared with the Open
      Approach?
AB  - BACKGROUND: Compared with open surgery, minimally invasive surgery for colon
      cancer has been shown to improve short-term outcomes and yield equivalent long
      term oncologic results. It remains to be seen if oncologic outcomes for the
      minimally invasive approach for rectal cancer are equivalent to traditional open
      rectal resection. METHODS: We conducted a systematic review of Medline, SCOPUS,
      and Cochrane databases. Relevant studies were selected using Preferred Reporting
      Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Five key
      questions comparing minimally invasive and open oncologic outcomes for rectal
      cancer were specifically analyzed. A meta-analysis was not done due to
      heterogeneity of studies. RESULTS: Forty-five studies met inclusion criteria,
      including six randomized controlled trials. The laparoscopic approach to rectal
      resection was not more likely than the traditional open approach to have clear
      circumferential and distal margins, a complete total mesorectal excision grade,
      >= 12 lymph nodes in the resected specimen, reduced local recurrence rates, or
      reduced overall survival rates. Two randomized trials revealed that successful
      laparoscopic resection was not noninferior to open. CONCLUSIONS: Caution should
      be exercised when choosing surgical options for rectal cancer. Results of
      randomized trials could not prove that short-term oncologic outcomes of
      laparoscopic surgery were equivalent to those after open surgery even when
      performed by surgeons with laparoscopic expertise. However, reported long-term
      data have not shown a difference in outcomes between laparoscopic and open
      surgery. Future advances in minimally invasive technology may improve oncologic
      margins but these will require careful study and scrutiny.

PMID- 30187282
TI  - Response to Machado et al. re: Jahi McMath.

PMID- 30187283
TI  - Low-Dose Aspirin Upregulates Tyrosine Hydroxylase and Increases Dopamine
      Production in Dopaminergic Neurons: Implications for Parkinson's Disease.
AB  - Increasing the function of residual dopaminergic neurons in the nigra of PD
      patients is an important area of research as it may eventually compensate the
      loss. Although tyrosine hydroxylase (TH) is the rate-limiting enzyme in the
      dopamine (DA) biosynthesis pathway, there are no effective drugs/molecules to
      upregulate TH and increase the production of DA in nigral dopaminergic neurons.
      This study underlines the importance of aspirin in stimulating the expression of
      TH and increasing the level of DA in dopaminergic neurons. At low doses, aspirin
      increased the expression of TH and the production of DA in mouse MN9D
      dopaminergic neuronal cells. Accordingly, oral administration of aspirin
      increased the expression of TH in the nigra and upregulated the level of DA in
      striatum of normal C57/BL6 mice and aged A53T alpha-syn transgenic mice. Oral
      aspirin also improved locomotor activities of normal mice and A53T transgenic
      mice. While investigating mechanisms, we found the presence of cAMP response
      element (CRE) in the promoter of TH gene and the rapid induction of cAMP response
      element binding (CREB) activation by aspirin in dopaminergic neuronal cells.
      Aspirin treatment also increased the level of phospho-CREB in the nigra of
      C57/BL6 mice. The abrogation of aspirin-induced expression of TH by siRNA
      knockdown of CREB and the recruitment of CREB to the TH gene promoter by aspirin
      suggest that aspirin stimulates the transcription of TH in dopaminergic neurons
      via CREB. These results highlight a new property of aspirin in stimulating the TH
      DA pathway, which may be beneficial in PD patients. Graphical Abstract ?.

PMID- 30187284
TI  - Comparative Safety and Pharmacokinetic Evaluation of Three Oral Selenium
      Compounds in Cancer Patients.
AB  - Selenium (Se) compounds have demonstrated anticancer properties in both
      preclinical and clinical studies, with particular promise in combination therapy
      where the optimal form and dose of selenium has yet to be established. In a phase
      I randomised double-blinded study, the safety, tolerability and pharmacokinetic
      (PK) profiles of sodium selenite (SS), Se-methylselenocysteine (MSC) and seleno-l
      methionine (SLM) were compared in patients with chronic lymphocytic leukaemia and
      a cohort of patients with solid malignancies. Twenty-four patients received 400
      MUg of elemental Se as either SS, MSC or SLM for 8 weeks. None of the Se
      compounds were associated with any significant toxicities, and the total plasma
      Se AUC of SLM was markedly raised in comparison to MSC and SS. DNA damage
      assessment revealed negligible genotoxicity, and some minor reductions in
      lymphocyte counts were observed. At the dose level used, all three Se compounds
      are well-tolerated and non-genotoxic. Further analyses of the pharmacodynamic
      effects of Se on healthy and malignant peripheral blood mononuclear cells will
      inform the future evaluation of higher doses of these Se compounds. The study is
      registered under the Australian and New Zealand Clinical Trials Registry No:
      ACTRN12613000118707.

PMID- 30187285
TI  - The Influence of Cortical Porosity on the Strength of Bone During Growth and
      Advancing Age.
AB  - PURPOSE OF REVIEW: Bone densitometry provides a two-dimensional projected areal
      apparent bone mineral density that fails to capture the heterogeneity of bone's
      material composition and macro-, micro-, and nano-structures critical to its
      material and structural strength. Assessment of the structural basis of bone
      fragility has focused largely on trabecular bone based on the common occurrence
      of fragility fractures at sites with substantial amounts of trabecular bone. This
      review focuses on the contribution of cortical bone to bone fragility throughout
      life. RECENT FINDINGS: Accurately differentiating cortical and trabecular bone
      loss has important implications in quantifying bone fragility as these
      compartments have differing effects on bone strength. Recent advances in imaging
      methodology have improved distinction of these two compartments by (i)
      recognition of a cortico-trabecular transitional zone and (ii) quantifying bone
      microstructure in a region of interest that is a percentage of bone length rather
      than a fixed point. Additionally, non-invasive three-dimensional imaging methods
      allow more accurate quantification of changes in the cortical, trabecular, and
      cortico-trabecular compartments during growth, aging, disease, and treatment.
      Over 75% of the skeleton is assembled as cortical bone. Of all fragility
      fractures, ~ 80% are appendicular and involve regions rich in cortical bone and ~
      70% of all age-related appendicular bone loss is cortical and is mainly due to
      unbalanced intracortical remodeling which increases cortical porosity. The
      failure to achieve the optimal peak bone microstructure during growth due to
      disease and the deterioration in cortical and trabecular bone produced by bone
      loss compromise bone strength. The loss of strength produced by microstructural
      deterioration is disproportionate to the bone loss producing this deterioration.
      The reason for this is that the loss of strength increases as a 7th power
      function of the rise in cortical porosity and a 3rd power function of the fall in
      trabecular density (Schaffler and Burr in J Biomech. 21(1):13-6, 1988), hence the
      need to quantify bone microstructure.

PMID- 30187287
TI  - Pharmacy-Based Approach to Improving Heart Failure Medication Use by Older Adults
      with Limited Health Literacy: Learning from Interdisciplinary Experience.
AB  - Heart failure is a chronic disease requiring careful attention to self-care.
      Patients must follow instructions for diet and medication use to prevent or delay
      a decline in functional status, quality of life, and expensive care. However,
      there is considerable heterogeneity in heart failure patients' knowledge of
      important care routines, their cognition, and their health literacy, which
      predict the ability to implement self-care. Our interdisciplinary team of
      cognitive scientists with health literacy expertise, pharmacists, and physicians
      spent 18 years designing and testing protocols and materials to assist ambulatory
      heart failure patients with their care. Our approach is theory- as well as
      problem-driven, guided by our process-knowledge model of health literacy as it
      relates to self-care among older adult outpatients with either heart failure or
      hypertension. We used what we had learned from this model to develop a pharmacy
      based protocol and tailored patient instruction materials that were the central
      component of a randomized clinical trial. Our results showed improved adherence
      to cardiovascular medications, improved health outcomes and patient satisfaction,
      and direct cost reductions. These results demonstrate the value of our
      interdisciplinary efforts for developing strategies to improve instruction and
      communication with attention to health literacy, which are core components of
      pharmacy and other ambulatory healthcare services. We believe attention to health
      literacy with medication use will result in improved health outcomes for older
      adult patients with heart failure and other complex chronic diseases.

PMID- 30187286
TI  - Sentinel node evaluation in prostate cancer.
AB  - Sentinel lymph node (SLN) based pelvic lymph node dissection (PLND) in prostate
      cancer (PCa) is appealing over the time, cost and morbidity classically
      attributed to conventional PLND during radical prostatectomy. The initial report
      of feasibility of the SLN concept in prostate cancer was nearly 20 years ago.
      However, PLND based on the SLN concept, either SLN biopsy of a single node or
      targeted SLN dissection of multiple nodes, is still considered investigational in
      PCa. To better appreciate the challenges, and potential solutions, associated
      with SLN-based PLND in PCa, this review will discuss the rationale behind PLND in
      PCa and evaluate current SLN efforts in the most commonly diagnosed malignancy in
      men in the US.

PMID- 30187288
TI  - A Review of the Pharmacological and Clinical Profile of Newer Atypical
      Antipsychotics as Treatments for Bipolar Disorder: Considerations for Use in
      Older Patients.
AB  - Bipolar disorder prevalence rates vary in the older adult population (defined as
      age >= 65 years), ranging from 1% in community dwellers to as high as 8-10% in
      hospital inpatients. Although older agents, including lithium and valproic acid,
      offer significant antimanic efficacy, as supported by a recent randomized
      controlled trial (RCT), there is growing interest in using atypical
      antipsychotics to treat bipolar disorder in older adults. Newer atypical
      antipsychotics are of interest based on their tolerability and efficacy in the
      general adult bipolar population. The aim of this review was to systematically
      examine efficacy and tolerability of newer atypical antipsychotics for older
      adult bipolar disorder (OABD). We conducted a systematic search utilizing the
      MEDLINE, EMBASE, PsycINFO and Cochrane Library electronic databases, with the aim
      of identifying all RCTs comparing newer atypical antipsychotics approved by the
      US FDA since 2002 (including brexpiprazole, cariprazine, lurasidone, iloperidone,
      asenapine, paliperidone, and aripiprazole) with placebo or another comparator, in
      the treatment of any phase of bipolar disorder (including mania, depression or
      mixed episodes while used as an acute or maintenance treatment) in older adults
      (> 65 years). We found no RCT data on any of the examined agents. Hence, we
      changed our search criteria to include studies with a lower age cut-off (>= 55
      years), as well as the inclusion of post hoc studies. Two post hoc studies on
      lurasidone suggest its reasonable safety and efficacy profile in the acute and
      maintenance treatment of OABD; however, there are no pharmacoeconomic data on the
      use of lurasidone in the treatment of OABD. Research data from open-label studies
      on oral asenapine and aripiprazole as add-on therapy suggest that these two
      agents are adequately tolerated and improved symptoms of depression and mania in
      OABD; hence, there is an urgent need to conduct RCTs on these two agents. Lastly,
      we found no studies for the treatment of OABD with brexpiprazole, cariprazine,
      iloperidone, or paliperidone.

PMID- 30187289
TI  - Medication-Induced Xerostomia and Hyposalivation in the Elderly: Culprits,
      Complications, and Management.
AB  - Medication-induced xerostomia and hyposalivation will increasingly become oral
      health issues for older and geriatric patients because of the likely high
      prevalence of medication intake and polypharmacy, with a complex negative impact
      on other symptoms such as dysphagia, caries incidence, malnutrition, and quality
      of life. All healthcare professionals are encouraged to investigate dry mouth
      symptoms among their patients, since diagnosis can easily be performed within
      daily clinical practice. This practical article also provides a review of
      available treatment options, which include medication changes towards products
      with fewer xerogenic side effects or dose reductions, if possible, as well as
      multidisciplinary, preventive care-oriented approaches that consider all
      influencing factors and treatment of the oral symptoms. In addition, several
      topical agents and saliva substitutes are discussed that may provide symptomatic
      relief but need to be carefully adapted to each patient's situation in terms of
      usability and practicability and in the knowledge that therapeutic success varies
      with each individual. Innovative methods such as intraoral electrostimulation or
      topical application of anticholinesterase on the oral mucosa are also discussed.
      The most commonly prescribed pharmaceutical treatment options for dry mouth are
      pilocarpine (a parasympathomimetic agent with potent muscarinic, cholinergic
      salivation-stimulating properties) and cevimeline (a quinuclidine analogue with
      therapeutic and side effects similar to those of pilocarpine). These pharmaceutic
      treatment options are described in the context of older patients, where the
      highly prevalent cholinergic side effects, which include nausea, emesis,
      bronchoconstriction, among others, need to be thoroughly supervised by the
      healthcare professionals involved. Providing these therapeutic options to
      patients with medication-induced dry mouth will help improve their oral health
      and therefore maintain a better quality of life, general health, and well-being.

PMID- 30187290
TI  - Lower Prescription Rates in Centenarians with Heart Failure and Heart Failure and
      Kidney Disease Combined: Findings from a Longitudinal Cohort Study of Very Old
      Patients.
AB  - BACKGROUND: Centenarians are considered as models of successful aging and
      represent a special group of patients. The aim of this study was to analyze heart
      failure epidemiology and treatment trajectories in centenarians compared to
      nonagenarians (90-99 years of age) and octogenarians (80-89 years of age) with
      heart failure and with heart failure and kidney disease combined. METHODS: This
      cohort study used quarterly structured routine data from 1398 German insurants
      over 6 years prior to death (398 centenarians were compared with 500
      nonagenarians and 500 octogenarians). Of those, 525 individuals were diagnosed
      with heart failure before death; 164 had heart failure and kidney disease
      combined. Generalized estimation equations were used to assess the association of
      diagnoses of heart failure and other diseases with medication prescriptions.
      RESULTS: Across age groups, heart failure was significantly more prevalent in
      centenarians compared with octogenarians and nonagenarians. Prevalence of heart
      failure increased over time. Female sex [odds ratio (men) = 0.70, p = 0.024],
      kidney disease (odds ratio = 1.31, p < 0.001), and hypertension (odds ratio =
      1.52, p < 0.001) were all associated with heart failure. Overall, heart failure
      treatment changed significantly over time with an increased prescription rate of
      loop diuretics and a decreased rate of renin-angiotensin-system inhibitors.
      Centenarians were significantly less likely to receive treatment with renin
      angiotensin-system inhibitors, loop diuretics, or beta-blockers compared with
      nonagenarians and octogenarians. Furthermore, aldosterone inhibitors were seldom
      prescribed; If-channel and neprilysin inhibitors were not routinely used in our
      sample. For those with heart failure and kidney disease combined, our data
      revealed that the prevalence of kidney disease was lower in centenarians than in
      younger patients before death. However, differences in prescription rates across
      age groups were non-significant, although numerically large. Finally, half of the
      patients in all three age groups with heart failure and kidney disease received
      treatment with renin-angiotensin-system inhibitors; about two out of five
      patients received beta-blockers, while prescription rates of aldosterone
      inhibitors were low. CONCLUSIONS: While heart failure prevalence shows a
      continuous increase with age, prescription rates are lower in centenarians,
      emphasizing the need for further studies considering the quality of care and
      outcomes in this patient population. Disease management programs and trials are
      needed to develop guidelines that address the medically challenging treatment for
      very old patients with comorbid heart failure and kidney disease.

PMID- 30187292
TI  - Antihypertensive Treatment Patterns and Blood Pressure Control in Older Adults:
      Results from the Berlin Aging Study II.
AB  - BACKGROUND: Hypertension is highly prevalent in older adults and represents a
      major public health issue since recognition, awareness, treatment and control are
      insufficient. Analyses of prescription patterns in conjunction with clinical
      parameters can provide novel insights into the current practice of hypertension
      management and help to identify barriers to sufficient hypertension control.
      METHODS: A cross-sectional analysis was conducted. Prevalence of hypertension,
      patterns of antihypertensive therapy, and determinants of blood pressure (BP)
      control were examined in the Berlin Aging Study II cohort, including 1654
      community-dwelling older adults (60-85 years of age). RESULTS: Of the
      participants, 75.9% had hypertension; 40.6% of these were not prescribed BP
      medications. Lack of hypertension awareness, younger age, absence of
      comorbidities, not being on a statin, and not having visited a physician in the
      past 3 months were associated with lack of treatment. Forty-two percent of
      treated hypertensive individuals received monotherapy and 58.0% received
      combination therapy. Renin-angiotensin-aldosterone system (RAAS) inhibitors, and
      beta-blockers were most commonly prescribed, while calcium channel blockers were
      least prescribed. Only 38.5% of treated hypertensive individuals had their BP
      controlled to < 140/90 mmHg. Number and choice of BP medications were not
      predictive of BP control; neither were age, glycated hemoglobin (HbA1c), kidney
      function, or number of healthcare visits. However, female sex, lower low-density
      lipoprotein cholesterol (LDL-C) levels and current smoking, amongst others, were
      positively associated with BP control. There was evidence of significant effect
      modification by statins in the association of LDL-C and BP. CONCLUSION: The
      majority of older adults do not reach BP goals. Antihypertensive prescription
      patterns do not conform to current guidelines. Using more BP medications was not
      associated with higher odds of BP control. Lowering LDL-C might be favorable in
      terms of BP control.

PMID- 30187294
TI  - Trusting the Results of Model-Based Economic Analyses: Is there a Pragmatic
      Validation Solution?
AB  - Models have become a nearly essential component of health technology assessment.
      This is because the efficacy and safety data available from clinical trials are
      insufficient to provide the required estimates of impact of new interventions
      over long periods of time and for other populations and subgroups. Despite more
      than five decades of use of these decision-analytic models, decision makers are
      still often presented with poorly validated models and thus trust in their
      results is impaired. Among the reasons for this vexing situation are the
      artificial nature of the models, impairing their validation against observable
      data, the complexity in their formulation and implementation, the lack of data
      against which to validate the model results, and the challenges of short
      timelines and insufficient resources. This article addresses this crucial problem
      of achieving models that produce results that can be trusted and the resulting
      requirements for validation and transparency, areas where our field is currently
      deficient. Based on their differing perspectives and experiences, the authors
      characterize the situation and outline the requirements for improvement and
      pragmatic solutions to the problem of inadequate validation.

PMID- 30187295
TI  - Pedicle screw shift without loosening following instrumented posterior fusion:
      limitations of pedicle screw fixation.
AB  - The disc angle at the fused segment is extended in operative prone position, but
      eventually returns to preoperative neutral position within 6 months to 1 year.
      This study aimed to assess pedicle screw (PS) shift without loosening to identify
      the mechanism of the change in disc angle after posterior fusion for degenerative
      lumbar spondylolisthesis (DLS). Sixty-three consecutive patients who underwent
      facet fusion for L4 single-level DLS were retrospectively reviewed using computed
      tomography (CT) immediately after surgery and 6 months postoperatively. Twenty
      two patients (88 PSs) in whom the disc angle had decreased by more than 4 degrees
      at 6-month postoperative radiographic follow-up were selected to more readily
      identify and quantify PS shift. Six patients with PS loosening and/or nonunion
      were excluded. We reconstructed a CT plane, vertical to the cranial endplate of
      the vertebrae and passing through the cannula used for percutaneous PSs. Angle
      alpha, which is formed by the cranial endplate and the cannula on this plane, was
      measured. A change in angle alpha of more than 2 degrees  between the immediate
      postoperative period and the 6-month follow-up was defined as a PS shift. Angle
      alpha did not change by more than 2 degrees  in any of the 44 PSs in the upper
      vertebrae of the fused segment. In the lower vertebrae, angle alpha changed by
      more than 2 degrees  in 22 of 44 PSs. The change in angle alpha in the lower
      vertebrae (average, 2.3 degrees ) was significantly greater than that in the
      upper vertebrae (average, 0.2 degrees ) (P < 0.0001). The change in the disc
      angle was not relevant to clinical outcomes assessed by the Japanese Orthopaedic
      Association Back Pain Evaluation Questionnaire, the Roland-Morris Disability
      Questionnaire, and the visual analogue scale. The disc angle at the fused segment
      returned to preoperative neutral position due to PS shift without loosening,
      mainly in the lower vertebrae. PS shift is caused by bone remodeling in response
      to biomechanical load, similar to that in orthodontic tooth movement. As PS has
      limited ability to maintain a lordotic disc angle, even with the insertion of a
      cage, lumbar alignment will return to preoperative neutral position owing to cage
      subsidence or adjacent segment disease. These findings might indicate that it is
      not necessary to correct the spinal alignment for DLS.

PMID- 30187291
TI  - Commonly Initiated Opioids and Risk of Fracture Hospitalizations in United States
      Nursing Homes.
AB  - OBJECTIVES: The aim of this study was to estimate the comparative safety of
      initiating commonly used opioids among older, long-stay United States nursing
      home residents with fracture hospitalizations. METHODS: We conducted a new-user
      retrospective cohort study of nursing home residents initiating short-acting
      oxycodone, hydrocodone, or tramadol by merging the 2011-2013 Minimum Data Set 3.0
      to Medicare hospitalization and pharmacy claims. Residents (>= 65 years, no
      cancer or hospice use) contributed treatment episodes (> 120 days with no prior
      opioid claims) and were followed for 180 days until incident fracture
      hospitalization (hip, femur, humerus, pelvis, radius/ulna), death (competing
      risk), treatment changes (e.g., discontinuation), or administrative censoring.
      Competing risks models with inverse probability of treatment weighting were used
      to estimate subdistribution hazard ratios (HRSD) and 95% confidence intervals
      (CI). RESULTS: Overall, 110,862 residents contributed 134,432 treatment episodes:
      14,373 oxycodone; 69,182 hydrocodone; and 50,877 tramadol initiators. The
      incidences of fracture hospitalizations per 100 person-years were 9.4 (95% CI 7.5
      11.7) for oxycodone, 7.9 (95% CI 7.1-8.8) for hydrocodone, and 5.0 (95% CI 4.3
      5.7) for tramadol initiators. In weighted models, oxycodone initiators had a
      similar rate of fractures to hydrocodone initiators (HRSD 1.08, 95% CI 0.79
      1.48). Tramadol initiators had lower fracture rates than hydrocodone initiators
      (HRSD 0.67, 95% CI 0.56-0.80). CONCLUSIONS: The lower rate of fractures that we
      documented among tramadol initiators compared with hydrocodone initiators is
      consistent, albeit attenuated compared with prior studies among community
      dwelling older adults. However, overall fracture rates were lower than in
      community settings, potentially due to the limited risk of falling in this
      population with limited mobility.

PMID- 30187297
TI  - Amino acids and peptides as reactants in multicomponent reactions: modification
      of peptides with heterocycle backbones through combinatorial chemistry.
AB  - In this study, amino acids and peptides were used as reactants in a Hantzsch
      multicomponent reaction in order to synthesize new structurally diverse molecules
      containing these synthons. As well, an applicable strategy for modification of
      these natural molecules with heterocycle backbones such as pyrimidine, xanthene
      and acridine is introduced. Using this method, a set of new amino acid- and
      peptide-functionalized heterocycles were synthesized in good to excellent yields
      under mild conditions. Furthermore, carbohydrates were used as substrates in the
      synthesis of some derivatives. Overall, this methodology allows the possibility
      of synthesis of large numbers of natural product-based libraries, using amino
      acids, peptides and carbohydrates through combinatorial chemistry.

PMID- 30187296
TI  - Long-term follow-up after surgical removal of meningioma of the inner third of
      the sphenoidal wing: outcome determinants and different strategies.
AB  - Meningioma arising in the inner third of the sphenoidal wing has been well
      recognized since the origin of neurosurgery, yet it still poses a formidable
      challenge for the surgeon. Treatment strategies can be optimized through a
      tailored approach to surgical timing and use of a non-surgical armamentarium. The
      aim of this study was to evaluate the long-term effect of different strategies on
      progression-free survival and overall survival. We examined the clinical records
      of brain tumor patients to assess determinants for surgery (extent of tumor
      removal, postoperative complications) and for progression-free survival and
      overall survival in relation to timing of surgery eventually followed by
      stereotactic radiosurgery (SRS). The records of 60 patients were retrospectively
      reviewed, from preoperative assessment to a median follow-up of 104 months. All
      were symptomatic with prevalently visual symptoms (42.2%), large tumors (median
      diameter 3.44 cm), extension into the cavernous sinus (38.3%), and severe
      vascular involvement of one or more encased or narrowed vessels (50%). Subtotal
      removal was achieved in 40% of cases, mainly determined by cavernous sinus and
      vascular involvement; neurological complications occurred in 18.3% (persistent in
      6.7% due to oculomotor and vascular injury). The overall rate of symptom
      improvement was 32.3% at 3 months and 49.5% at 12 months. Radiological monitoring
      prevented clinical progression; tumor progression occurred in 11.7% of cases.
      There were significant differences in progression-free survival between patients
      with (median 46 months) and those without (median 104 months) recurrence (p =
      0.002): 12.5% after total removal, 6.2% after subtotal removal and adjuvant SRS,
      and 28.5% after subtotal removal and observation. The related Kaplan-Meier
      survival curve showed no significant difference between the three strategies.
      Further, disease progression after recurrence was noted in 28.6% of cases, but
      overall survival was not influenced by either tumor recurrence or type of
      treatment. Treatment failure was recorded in four cases (6.7%): one perioperative
      death and three later on. Surgery is the mainstay for the treatment of
      symptomatic meningioma and to restore neurological function; however,
      resectability is limited by vascular and cavernous sinus involvement. Careful
      postoperative monitoring prevented clinical progression and adjuvant or
      adjunctive SRS proved effective in tumor control. A low surgical complication
      rate and excellent long-term outcomes were achieved with this strategy.

PMID- 30187293
TI  - Sleep, Diet, and Cardiometabolic Health Investigations: a Systematic Review of
      Analytic Strategies.
AB  - PURPOSE OF REVIEW: Poor sleep is a risk factor for cardiometabolic morbidity. The
      relationship of sleep and cardiometabolic health could be confounded, mediated,
      or modified by diet, yet the incorporation of diet in sleep-cardiometabolic
      health studies is inconsistent. This rapid systematic literature review evaluates
      the conceptualization of diet as a confounder, mediator, or effect modifier
      within sleep-cardiometabolic health investigations, and the statistical
      approaches utilized. RECENT FINDINGS: Of 4692 studies identified, 60 were
      retained (28 adult, 32 pediatric). Most studies included diet patterns, quality,
      or energy intake as confounders, while a few examined these dietary variables as
      mediators or effect modifiers. There was some evidence, mostly in pediatric
      studies, that inclusion of diet altered sleep-cardiometabolic health
      associations. Diet plays a diverse role within sleep-cardiometabolic health
      associations. Investigators should carefully consider the conceptualization of
      diet variables in these relationships and utilize contemporary statistical
      approaches when applicable.

PMID- 30187298
TI  - Otoprotective Effects of Stephania tetrandra S. Moore Herb Isolate against
      Acoustic Trauma.
AB  - Noise is the most common occupational and environmental hazard, and noise-induced
      hearing loss (NIHL) is the second most common form of sensorineural hearing
      deficit. Although therapeutics that target the free-radical pathway have shown
      promise, none of these compounds is currently approved against NIHL by the United
      States Food and Drug Administration. The present study has demonstrated that
      tetrandrine (TET), a traditional Chinese medicinal alkaloid and the main chemical
      isolate of the Stephania tetrandra S. Moore herb, significantly attenuated NIHL
      in CBA/CaJ mice. TET is known to exert antihypertensive and antiarrhythmic
      effects through the blocking of calcium channels. Whole-cell patch-clamp
      recording from adult spiral ganglion neurons showed that TET blocked the
      transient Ca2+ current in a dose-dependent manner and the half-blocking
      concentration was 0.6 + 0.1 MUM. Consistent with previous findings that
      modulations of calcium-based signaling pathways have both prophylactic and
      therapeutic effects against neural trauma, NIHL was significantly diminished by
      TET administration. Importantly, TET has a long-lasting protective effect after
      noise exposure (48 weeks) in comparison to 2 weeks after noise exposure. The
      otoprotective effects of TET were achieved mainly by preventing outer hair cell
      damage and synapse loss between inner hair cells and spiral ganglion neurons.
      Thus, our data indicate that TET has great potential in the prevention and
      treatment of NIHL.

PMID- 30187300
TI  - The way to a man's heart is through the stomach.

PMID- 30187299
TI  - Abernethy malformation: Single-center experience from India with review of
      literature.
AB  - Abernethy malformation is a rare congenital anomaly in which there is direct
      communication between the portal and systemic venous circulation. The clinical
      presentation ranges from asymptomatic with incidental detection on imaging to
      secondary complications of disease or related to associate anomalies. This is a
      retrospective analysis of data from nine patients with Abernethy malformation at
      a single center. This is a referral center for Pediatric Cardiology and for
      Hepatobiliary and Pancreatic Surgery. The patients presented to the Pulmonary
      Hypertension Clinic/the Hepatobiliary Surgery Clinic. Out of nine patients, four
      were male. Type II Abernethy malformation was present in five patients whereas
      three patients had type I malformation. One of the patients had communication
      between inferior mesenteric vein and internal iliac vein. Five out of nine
      patients were erroneously diagnosed as idiopathic primary pulmonary hypertension
      and were treated with vasodilators. One patient required living donor liver
      transplant. One patient was managed with surgical shunt closure whereas two
      patients required transcatheter shunt closure. The rest of the patients were
      managed conservatively. Abernethy malformation is more common than previously
      thought and the diagnosis is often missed. There are various management options
      for Abernethy malformation, which includes surgical or transcatheter shunt
      closure and liver transplant. Management of Abernethy malformation depends upon
      type, presentation, and size of shunt.

PMID- 30187301
TI  - Truth is in the eye of the beholder: Perception of the Muller-Lyer illusion in
      dogs.
AB  - Visual illusions are objects that are made up of elements that are arranged in
      such a way as to result in erroneous perception of the objects' physical
      properties. Visual illusions are used to study visual perception in humans and
      nonhuman animals, since they provide insight into the psychological and cognitive
      processes underlying the perceptual system. In a set of three experiments, we
      examined whether dogs were able to learn a relational discrimination and to
      perceive the Muller-Lyer illusion. In Experiment 1, dogs were trained to
      discriminate line lengths using a two-alternative forced choice procedure on a
      touchscreen. Upon learning the discrimination, dogs' generalization to novel
      exemplars and the threshold of their abilities were tested. In the second
      experiment, dogs were presented with the Muller-Lyer illusion as test trials,
      alongside additional test trials that controlled for overall stimulus size. Dogs
      appeared to perceive the illusion; however, control trials revealed that they
      were using global size to solve the task. Experiment 3 presented modified stimuli
      that have been known to enhance perception of the illusion in other species.
      However, the dogs' performance remained the same. These findings reveal evidence
      of relational learning in dogs. However, their failure to perceive the illusion
      emphasizes the importance of using a full array of control trials when examining
      these paradigms, and it suggests that visual acuity may play a crucial role in
      this perceptual phenomenon.

PMID- 30187302
TI  - Biochemical characterization of photosystem I complexes having different subunit
      compositions of fucoxanthin chlorophyll a/c-binding proteins in the diatom
      Chaetoceros gracilis.
AB  - Diatoms are dominant phytoplankton in aquatic environments and have unique light
      harvesting apparatus, fucoxanthin chlorophyll a/c-binding protein (FCP). Diatom
      photosystem I (PSI) interacts with specific FCPs (FCPI); however, it remains
      unclear how PSI cores receive excitation energy from FCPI. To analyze the energy
      transfer dynamics, it is necessary to isolate both PSI cores and PSI-FCPI
      complexes. In this study, we prepared three PSI complexes, which are PSI-FCPI
      membrane fragments, detergent-solubilized PSI-FCPI supercomplexes and PSI core
      like complexes, from the marine centric diatom, Chaetoceros gracilis, and
      examined their biochemical properties. Both the PSI-FCPI membrane fragments and
      supercomplexes showed similar subunit compositions including FCPI, whereas the
      PSI complexes were devoid of most FCPI subunits. The purity and homogeneity of
      the two detergent-solubilized PSI preparations were verified by clear-native PAGE
      and electron microscopy. The difference of pigment contents among the three PSI
      samples was shown by absorption spectra at 77 K. The intensity in the whole
      spectrum of PSI-FCPI membranes was much higher than those of the other two
      complexes, while the spectral shape of PSI complexes was similar to that of
      cyanobacterial PSI core complexes. 77-K fluorescence spectra of the three PSI
      preparations exhibited different spectral shapes, especially peak positions and
      band widths. Based on these observations, we discuss the merits of three PSI
      preparations for evaluating excitation energy dynamics in diatom PSI-FCPI
      complexes.

PMID- 30187303
TI  - Photorespiration is complemented by cyclic electron flow and the alternative
      oxidase pathway to optimize photosynthesis and protect against abiotic stress.
AB  - Optimization of photosynthetic performance and protection against abiotic stress
      are essential to sustain plant growth. Photorespiratory metabolism can help
      plants to adapt to abiotic stress. The beneficial role of photorespiration under
      abiotic stress is further strengthened by cyclic electron flow (CEF) and
      alternative oxidase (AOX) pathways. We have attempted to critically assess the
      literature on the responses of these three phenomena-photorespiration, CEF and
      AOX, to different stress situations. We emphasize that photorespiration is the
      key player to protect photosynthesis and upregulates CEF as well as AOX. Then
      these three processes work in coordination to protect the plants against
      photoinhibition and maintain an optimal redox state in the cell, while providing
      ATP for metabolism and protein repair. H2O2 generated during photorespiratory
      metabolism seems to be an important signal to upregulate CEF or AOX. Further
      experiments are necessary to identify the signals originating from CEF or AOX to
      modulate photorespiration. The mutants deficient in CEF or AOX or both could be
      useful in this regard. The mutual interactions between CEF and AOX, so as to keep
      their complementarity, are also to be examined further.

PMID- 30187304
TI  - Epilepsia partialis continua following a Western variant tick-borne encephalitis.
AB  - Epilepsia partialis continua (EPC) is a rare entity, first described in 1894 by
      Kozevnikov, as a variant of simple focal motor status epilepticus. EPC is most
      frequently characterized by motor symptoms, but as recently described, non-motor
      manifestations may occur, such as somatosensory symptoms or aura continua. EPC in
      adults has been attributed to various etiologies: infectious, vascular,
      neoplastic, and metabolic. According to the recent definition, we reported a case
      of EPC with behavioral symptoms, following a tick-borne encephalitis (TBE)
      contracted in an endemic area (North Eastern Italy). Patient's symptom was a
      poorly localized "whole body sensation", which is reported as a condition
      occurring only in frontal lobe epilepsy. Patient's EEG showed a left frontal
      predominance of epileptiform discharges. Literature highlighted the importance of
      the Far-eastern TBE variant as a cause of EPC, since no Western variant TBE cases
      are reported. In contrast to what was claimed so far, our case demonstrates that
      not only the Far-eastern TBE variant, but also Western variant TBE is a cause of
      EPC. Prognosis of EPC depends largely on the underlying etiology, and it is
      frequently drug-resistant. Our patient was treated with intravenous
      levetiracetam, with a subsequent clinical recovery and a disappearance of
      epileptiform discharges. The rapid clinic and electroencephalographic response to
      levetiracetam confirm that it can be a promising therapeutic option for treatment
      of EPC.

PMID- 30187305
TI  - A Novel SYNJ1 Mutation in a Tunisian Family with Juvenile Parkinson's Disease
      Associated with Epilepsy.
AB  - Mutations in SYNJ1 gene have been described in few families with juvenile
      atypical Parkinson disease (PD). This gene encodes for "Synaptojanin 1," an
      enzyme playing a major role in the phosphorylation and the recycling of synaptic
      vesicles. In this study, we report two siblings, from a consanguineous Tunisian
      family, presenting juvenile PD. Both siblings developed mild Parkinsonism at 16
      and 21 years old respectively. One patient had generalized tonic-clonic seizures
      since the age of 7 years. There was no evidence of sleep or autonomic
      dysfunctions and psychiatric disorders in both cases, but they developed a
      moderate cognitive impairment. They kept a good respond to low doses of levodopa
      treatment with no dyskinesia or motor fluctuations. We designed an NGS-based
      screening of 22 currently most prevalent parkinsonism-associated genes. Genetic
      study revealed a novel compound heterozygous mutation (p.Leu1406Phefs*42 and
      p.Lys1321Glu) in SYNJ1 gene. The p.Lys1321Glu mutation is located in the proline
      rich domain and leads to a significant change in the 3D structure of the protein
      (RMS = 12.58 A). The p.Leu1406Phefs*42 mutation disrupt the AP2 binding sites and
      subsequently disable synaptic and vesicle endocytic recycling in neurons. This is
      the first report of mutation in the C-terminal domain of Synaptojanin 1 protein
      causing mild juvenile PD with generalized seizures, cognitive impairment, and
      good respond to levodopa treatment.

PMID- 30187306
TI  - The efficacy of Ritalin in ADHD children under neurofeedback training.
AB  - Current research has shown that neurofeedback (NF) is a viable treatment for
      attention deficit hyperactivity disorder (ADHD), however having pharmacological
      approach alongside such stimulants is still inevitable. Therefore, the purpose of
      this study is the comparison of neurofeedback with Ritalin and without Ritalin in
      treating children with ADHD. This study was causal-comparative in design.
      Participants were children aged 5-10 years with ADHD; seven participants were in
      neurofeedback group with Ritalin and seven in neurofeedback without Ritalin group
      according to random split and parent's conformation. Clinical Q, Conner's
      continuous performance test (CPT), and WISC-R were used before and after
      treatment. For analyzing data, we used descriptive statistical and Mann Whitney U
      tests. Results showed that even if the two groups were modified in all
      components, modifications of commission and reaction time of the CPT and F4
      theta/alpha of the clinical Q were more accurate in NF with Ritalin treatment
      rather than the other group. These findings suggest that neurofeedback is
      efficient in improving some of the behavioral concomitants of ADHD in children
      whose parents favored non-pharmacological treatment, but Ritalin and
      neurofeedback combination is more efficient. So, multimodal approach is strongly
      recommended for ADHD treatment.

PMID- 30187307
TI  - Association of the rs1611115 polymorphism in DBH gene with Parkinson's disease: a
      meta-analysis.
AB  - A meta-analysis was performed to assess the association between the dopamine beta
      hydroxylase (DBH) rs1611115 genetic polymorphism and Parkinson's disease (PD). A
      comprehensive search was conducted to identify all case-control or cohort
      studies. The fixed or random effect-pooled measure was selected on the basis of a
      homogeneity test among studies. Heterogeneity among studies was evaluated using
      the I2. We performed sensitivity analyses to evaluate the robustness of the
      results. Publication bias was estimated using Egger's linear regression test.
      Five case-control studies corresponded to the inclusion criteria comprising 3926
      patients and 3542 controls which were included in the present meta-analysis. Our
      meta-analysis showed no significant association between DBH rs1611115 genetic
      polymorphism and risk of PD in the codominant (REM, OR = 1.017, 95%CI = 0.854
      1.210), dominant (REM, OR = 0.989, 95%CI = 0.826-1.185), and recessive (REM, OR =
      1.007, 95%CI = 0.657-1.542) models. Moreover, in the subgroup analysis based on
      region (Asia and Europe), no significant associations were observed in Asia or
      Europe. This meta-analysis suggests that the DBH rs1611115 genetic polymorphism
      might not be associated with PD.

PMID- 30187309
TI  - Deadly outbreak of chickenpox at district Faisalabad, Pakistan: possible causes,
      and preventive way forward.
AB  - This article details our recommendations for the deadly outbreak of chickenpox to
      consider the additional referral of the absence of a monitoring system of
      prevention and control along with poor vaccination system for children in low
      resource settings. The recent spread of chickenpox outbreak in Pakistan has
      claimed dozens of lives. The deaths in this current outbreak in quick successions
      are beyond understanding. Re-emergence of chickenpox in the area has raised many
      questions. Keeping in view the spread of chickenpox mainly in Faisalabad and its
      international reputation in trading, chickenpox breakout needs international
      attention to control its spread. It should be taken as an eye opener for the
      Government of Pakistan and government should develop and implement Centralized
      Infectious Disease Reporting Information Management System that will help to
      narrow down the pathogens as far as the epidemics are concerned and also for
      early preventive and countermeasure response.

PMID- 30187308
TI  - A Brief Historical Perspective on the Pathological Consequences of Excessive Type
      I Interferon Exposure In vivo.

PMID- 30187310
TI  - Isolation of microsatellite loci for the endangered vermetid gastropod Dendropoma
      lebeche using Illumina MiSeq next generation sequencing technology.
AB  - Dendropoma petraeum, considered the primary vermetid reef-building species in the
      Mediterranean, has recently been shown to be a species complex of at least four
      cryptic species. These species have highly restricted, non-overlapping
      distributions, causing concern for their conservation status. To better study the
      genetic diversity of these populations, we selected one of these species,
      Dendropoma lebeche (Templado et al. in Mediterr Mar Sci 17(1):13-31, 2016), which
      is restricted to the western Mediterranean, for microsatellite marker development
      using Illumina MiSeq. We provide an initial survey of 29 polymorphic
      microsatellite loci for D. lebeche. Genetic analyses identified 2-11 alleles per
      locus across the 30 samples examined. Observed and expected heterozygosities
      ranged from 0.067 to 0.800 and 0.064 to 0.770, respectively. None of the loci
      deviated from Hardy-Weinberg equilibrium or showed signs of being under selective
      pressure. Significant linkage disequilibrium was found between two loci. We also
      show the cross-species amplification of these microsatellite markers in the other
      three species of the complex, the Tyrrhenian-Sicilian lineage, D. cristatum
      (Biondi, 1859), the Levantine lineage, D. anguliferum (Monterosato, 1878) and
      Dendropoma sp. found along the Ionian-Aegean coasts, suggesting their potential
      utility for future phylogenetic and evolutionary studies.

PMID- 30187311
TI  - Effect of explant type and plant growth regulators on callus induction, growth
      and secondary metabolites production in Cnidium officinale Makino.
AB  - This study reports the effect of explant type and plant growth regulators (PGRs)
      on callus induction in Cnidium officinale. Compared to stem, root explant showed
      maximum percent callus formation of 75% on Murashige and Skoog (MS) medium
      containing 2.3 uM 2,4-dichlorophenoxyacetic acid (2,4-D) and 2.2 uM benzyladenine
      (BA). At 30th day of callus culture on the said medium, callus fresh weight was
      sevenfold higher than other tested PGRs treatments. It was noted that MS medium
      supplemented with 27.1 uM 2,4-D showed the highest 0.30 mg g-1 DW of total
      phenols, while total flavonoids content reached to a maximum of 0.05 mg g-1 DW on
      the MS medium supplemented with 4.5 uM 2,4-D and 2.2 uM BA. Conversely, maximum
      (83.9%) DPPH free radical scavenging activity was observed in calli grown on the
      MS medium supplemented with 2.3 uM 2,4-D and 2.2 uM BA. The high-performance
      liquid chromatography (HPLC) analysis revealed higher phthalide content in callus
      than intact roots of in vitro plants. While 3-butylidenephthalide content in
      callus was comparable to the intact shoots and roots of in vitro grown C.
      officinale. The concentrations of 2,4-D played a significant role in the
      production of phthalide and 3-butylidenephthalide. Additional measures are
      recommended to further enhance their production in vitro.

PMID- 30187313
TI  - Phenanthrene Fluorescence Quenching in Aqueous Sodium Dodecyl Sulphate (SDS) and
      Determination of Important Metal Ions.
AB  - In this work fluorescence quenching of phenanthrene by heavy metal ions (Fe3+,
      Cu2+, Cr3+ Pb2+, Ni2+) was studied in aqueous solution of sodium dodecyl sulphate
      (SDS). Fluorescence quenching was higher in lower SDS concentration and decreased
      with the increase in SDS concentration. Phenanthrene quenching by heavy metal
      ions were explained by Stern-Volmer equations and the Stern-Volmer constants were
      observed in the order Fe3+ > Cu2+ > Cr3+ > Pb2+ > Ni2+ respectively. Stern-Volmer
      constants reflect the sensitivity of the method for the studied metal ions. Limit
      of detection which was calculated as three time standard deviation of the blank
      for n = 10 (3*SD) ranged from 1.504*10-6-1.113*10-5 molL-1and limit of
      quantification which was calculated as ten times standard deviation of the blank
      for n = 10 (10*SD) ranged from 5.013*10-6-3.371*10-5 mol L-1. Phenanthrene
      fluorescence quenching by the studied metal ions shows good reproducibility and
      the used of anionic surfactant increases the fluorescence quenching of
      phenanthrene by heavy metal ions. This method could be very effective for the
      determination of metal ions.

PMID- 30187312
TI  - Green Synthesized Carbon Quantum Dots from Polianthes tuberose L. Petals for
      Copper (II) and Iron (II) Detection.
AB  - In this work carbon quantum dots (CQDs) are synthesized via a simple, low cost
      and as well as green way using tuberose (Polianthes tuberose L.) petals as the
      carbon source for the first time. We have not done any surface modification to
      the prepared CQDs although we directly employed this as fluorescent probe for the
      sensitive and selective detection of Fe2+ and Cu2+ ions. Both these ions
      drastically quench the emission intensity of the CQDs; in case of Cu2+ ions
      quenched CQDs EDTA results in regaining the fluorescence property but for Fe2+
      ions quenched CQDs no such effect of EDTA is found. The limit of detection (LOD)
      is observed to be 200 nM in case of Cu2+ which is much lower than the safe limit
      provided by the WHO in drinking water. Hence the CQDs prepared in this simple and
      low cost method may find an important role in monitoring the water quality. The
      quantum yield of the CQDs prepared in our method is around 3%. Transmission
      electron microscope shows picture of nicely shaped CQDs with average size ~ 4 nm.

PMID- 30187314
TI  - Using an Existing DICOM Infrastructure to Enhance the Availability, Quality, and
      Efficiency of Imaging Throughout the Healthcare Enterprise.
AB  - Managing the capture, label, and storage of medical imaging performed by
      nonradiology departments at the point of care has become a core issue for many
      health systems. In contrast to the well-organized and controlled workflows
      enjoyed by radiology, nonradiology imaging and its associated workflows are often
      chaotic. Left on their own, many nonradiology departments simply fend for
      themselves, finding ways to capture and store their imaging that meets the
      critical need, while falling far short of the ideal. The focus of this study was
      to build and implement a software solution for nonradiology image management for
      a large, multi-specialty health system. Once developed, the solution was deployed
      and results were collected from users via survey and by comparison of available
      pre- and post-implementation statistics. The results show high rates of
      satisfaction among users, evidence of cost savings from decommissioning redundant
      systems, staff time savings, and fewer storage failures.

PMID- 30187315
TI  - Automatic Mapping of CT Scan Locations on Computational Human Phantoms for Organ
      Dose Estimation.
AB  - To develop an algorithm to automatically map CT scan locations of patients onto
      computational human phantoms to provide with patient-specific organ doses. We
      developed an algorithm that compares a two-dimensional skeletal mask generated
      from patient CTs with that of a whole body computational human phantom. The
      algorithm selected the scan locations showing the highest Dice Similarity
      Coefficient (DSC) calculated between the skeletal masks of a patient and a
      phantom. To test the performance of the algorithm, we randomly selected five sets
      of neck, chest, and abdominal CT images from the National Institutes of Health
      Clinical Center. We first automatically mapped scan locations of the CT images on
      a computational human phantom using our algorithm. We had several radiologists to
      manually map the same CT images on the phantom and compared the results with the
      automated mapping. Finally, organ doses for automated and manual mapping
      locations were calculated by an in-house CT dose calculator and compared to each
      other. The visual comparison showed excellent agreement between manual and
      automatic mapping locations for neck, chest, and abdomen-pelvis CTs. The
      difference in mapping locations averaged over the start and end in the five
      patients was less than 1 cm for all neck, chest, and AP scans: 0.9, 0.7, and 0.9
      cm for neck, chest, and AP scans, respectively. Five cases out of ten in the neck
      scans show zero difference between the average manual and automatic mappings.
      Average of absolute dose differences between manual and automatic mappings was
      2.3, 2.7, and 4.0% for neck, chest, and AP scans, respectively. The automatic
      mapping algorithm provided accurate scan locations and organ doses compared to
      manual mapping. The algorithm will be useful in cases requiring patient-specific
      organ dose for a large number of patients such as patient dose monitoring,
      clinical trials, and epidemiologic studies.

PMID- 30187316
TI  - OIPAV: an Integrated Software System for Ophthalmic Image Processing, Analysis,
      and Visualization.
AB  - Ophthalmic medical images, such as optical coherence tomography (OCT) images and
      color photo of fundus, provide valuable information for clinical diagnosis and
      treatment of ophthalmic diseases. In this paper, we introduce a software system
      specially oriented to ophthalmic images processing, analysis, and visualization
      (OIPAV) to assist users. OIPAV is a cross-platform system built on a set of
      powerful and widely used toolkit libraries. Based on the plugin mechanism, the
      system has an extensible framework. It provides rich functionalities including
      data I/O, image processing, interaction, ophthalmic diseases detection, data
      analysis, and visualization. By using OIPAV, users can easily access to the
      ophthalmic image data manufactured from different imaging devices, facilitate
      workflows of processing ophthalmic images, and improve quantitative evaluations.
      With a satisfying function scalability and expandability, the software is
      applicable for both ophthalmic researchers and clinicians.

PMID- 30187318
TI  - Pancreatic Metastasis from Endometrial Carcinoma.

PMID- 30187317
TI  - Improving image quality around subtle lung nodules by reducing artifacts in
      similar subtraction imaging.
AB  - Similar subtraction imaging is useful for the detection of lung nodules; however,
      some artifacts on similar subtraction images reduce their utility. The authors
      attempted to improve the image quality of similar subtraction images by reducing
      artifacts caused by differences in image contrast and sharpness between two
      images used for similar subtraction imaging. Image contrast was adjusted using
      the histogram specification technique. The differences in image sharpness were
      compensated for using a pixel matching technique. The improvement in image
      quality was evaluated objectively based on the degree of artifacts and the
      contrast-to-noise ratio (CNR) of the lung nodules. The artifacts in similar
      subtraction images were reduced in 94% (17/18) of cases, and CNR was improved in
      83% (15/18) of cases. The results indicate that the combination of histogram
      specification and pixel matching techniques is potentially useful in improving
      image quality in similar subtraction imaging.

PMID- 30187319
TI  - Risk Factors Associated with Lymph Node Metastasis for Early Gastric Cancer
      Patients Who Underwent Non-curative Endoscopic Resection: a Systematic Review and
      Meta-analysis.
AB  - BACKGROUND: Recently, increased evidence indicated that additional surgery should
      be performed in highly selected patients with non-curative endoscopic resection.
      In this study, we performed a systematic review and meta-analysis to evaluate the
      risk factors associated with lymph node metastasis for the patients with non
      curative endoscopic resection of early gastric cancer. METHODS: The related
      studies were identified by searching PubMed and Embase databases. According to
      the status of lymph node metastasis, all patients were classified into node
      negative group and node-positive group. The relevant clinicopathologic factors
      were extracted, and the pooled odds ratio (OR) and 95% confidence interval (CIs)
      were assessed using a fixed effects model or random effects model. RESULTS: A
      total of nine relevant studies involving 1720 early gastric cancer patients who
      underwent additional surgery following the non-curative endoscopic resection were
      included in this meta-analysis. The results indicated that deeper submucosal
      invasion (SM2) (OR 3.44, 95% CI 1.94-6.10, P < 0.001; I2 = 0%), positive vertical
      margin (OR 2.35, 95% CI 1.57-3.53, P < 0.001; I2 = 0%), lymphatic invasion (OR
      11.06, 95% CI 5.47-22.36, P < 0.001; I2 = 0%), and vascular invasion (OR 2.79,
      95% CI 1.68-4.64, P < 0.001; I2 = 0%) were significantly associated with lymph
      node metastasis for these patients. However, horizontal margin, tumor size,
      differentiation type, and ulceration were not identified as risk factors
      associated with lymph node metastasis. CONCLUSION: Lymphatic invasion, vascular
      invasion, deeper submucosal invasion (SM2), and positive vertical margin should
      be strongly considered in selecting the candidates for additional surgery
      treatment.

PMID- 30187320
TI  - Strengths, Weaknesses, Opportunities, and Threats of Centralized Pancreatic
      Surgery: a Single-Center Analysis of 3000 Consecutive Pancreatic Resections.
AB  - BACKGROUND: Pancreatic surgery at high-volume centers has undergone major changes
      over the last decades. However, the quality of surgery remains to be considered
      as one important factor for achieving long-term survival especially in patients
      at advanced stages of disease. METHODS: Between January 1990 and June 2017, 3000
      consecutive patients have undergone pancreatic resections at our institution.
      Relevant postoperative data and histopathological findings as well as overall
      survival were analyzed. In addition, a SWOT (strengths, weaknesses,
      opportunities, threats) analysis of pancreatic surgery at high-volume centers was
      performed. RESULTS: A total of 2218 pancreatic head resections (74%), 494 distal
      pancreatectomies (16%), 200 total pancreatectomies (7%), and 88 other resections
      (3%) were performed within our study period. Despite additional vascular
      resections in 265 patients (9%) and additional liver resections in 167 patients
      (6%), overall perioperative mortality did not exceed 3%. Overall survival
      strongly depended on the underlying disease, as well as on lymph node stage (p =
      < 0.001) and surgical radicality (p = < 0.001). CONCLUSIONS: The decentralization
      of pancreatic surgery over the last decades has led to a focus on high-volume
      centers to perform extended procedures in complex patients. The present SWOT
      analysis underlines the significance of a centralization of pancreatic surgery
      for patient safety and to increase the chance of long-term survival.

PMID- 30187321
TI  - Megabowel and Giant Fecaloma: a Surgical Condition?

PMID- 30187322
TI  - Blood Type as a Predictor of High-Grade Dysplasia and Associated Malignancy in
      Patients with Intraductal Papillary Mucinous Neoplasms.
AB  - BACKGROUND: Intraductal papillary mucinous neoplasms (IPMNs) are precursor
      lesions to the development of pancreatic adenocarcinoma. We determined if non-O
      blood groups are more common in patients with IPMN and if blood group is a risk
      factor for progression to invasive pancreatic cancer among patients with IPMN.
      METHODS: The medical records were reviewed of all patients undergoing resection
      of an IPMN at Johns Hopkins Hospital from June 1997 to August 2016. Potential
      risk factors of high-grade dysplasia and associated adenocarcinoma were
      identified through a multivariate logistic regression model. RESULTS: Seven
      hundred and seventy-seven patients underwent surgical resection of an IPMN in
      which preoperative blood type was known. Sixty-two percent of IPMN patients had
      non-O blood groups (vs. 57% in two large US reference cohorts, P = 0.002). The
      association between non-O blood group was significant for patients with IPMN with
      low- or intermediate-grade dysplasia (P < 0.001), not for those with high-grade
      dysplasia (P = 0.68). Low- and intermediate-grade IPMNs were more likely to have
      non-type O blood compared to those with high-grade IPMN and/or associated
      invasive adenocarcinoma (P = 0.045). Blood type O was an independent predictor of
      having high-grade dysplasia without associated adenocarcinoma (P = 0.02), but not
      having associated invasive cancer (P = 0.72). The main risk factor for
      progression to invasive cancer after surgical resection was IPMN with high-grade
      dysplasia (P = 0.002). CONCLUSION: IPMN patients are more likely to have non-O
      blood groups than controls, but type O blood group carriers had higher odds of
      having high-grade dysplasia in their IPMN. These results indicate blood group
      status may have different effects on the risk and progression of IPMNs.

PMID- 30187323
TI  - Enhanced Recovery Program for Colorectal Surgery: a Focus on Elderly Patients
      Over 75 Years Old.
AB  - BACKGROUND: An enhanced recovery after surgery (ERAS) protocol can effectively
      improve perioperative outcomes in surgical patients by reducing complication
      rates and hospital stay. However, its application in elderly patients has yielded
      contradictory results. The aim of this study was to evaluate surgical outcomes in
      a cohort of elderly patients undergoing colorectal resection in our unit before
      and after the introduction of ERAS. METHODS: From 328 patients undergoing
      colorectal surgery in our unit over a 2-year period (2015-2016), 114 patients >=
      75 years of age were selected. The patients were categorized according to
      perioperative treatment as pre-ERAS and ERAS patients (respectively, 53 vs 61
      patients), and the groups were compared for statistical purposes. Outcome
      measures included length of hospital stay, recovery of bowel functions, oral
      feeding, postoperative complications, and readmissions. Compliance with the ERAS
      protocol was also measured. RESULTS: Groups were homogeneous for all the clinical
      surgical variables, with the sole exception of the Charlson index, which was more
      severe in the ERAS group (p = 0.012). Compared with control patients, ERAS
      patients reported improved functional recovery (time to first flatus, stool, and
      oral feeding; p < 0.001). Hospital stay was reduced in ERAS patients overall and
      by side of resection, excluding rectal procedures. No differences were observed
      regarding postoperative complications. Of note, an optimal adherence to the
      protocol was reported, with 79% of items respected. CONCLUSIONS: ERAS can be
      considered safe in elderly patients undergoing colorectal surgery with a high
      comorbidity index, providing a reduction in hospital stay and improving short
      term postoperative outcomes. Finally, the protocol application was feasible, with
      a high adherence to the items in this subset of patients.

PMID- 30187324
TI  - Sleeve Gastrectomy and Roux-En-Y Gastric Bypass Lead to Comparable Changes in
      Body Composition in a Multiethnic Asian Population.
AB  - BACKGROUND: Changes in body composition after bariatric surgery such as a
      sustained loss of body fat are often associated with an inevitable loss of fat
      free mass. This can contribute to an undesirable disturbance in resting metabolic
      rate and weight maintenance. Our aim was to study changes in body composition in
      a multiethnic Asian cohort following bariatric surgery and to identify
      differences between laparoscopic sleeve gastrectomy and laparoscopic Roux-en-Y
      gastric bypass. METHODS: A retrospective review of prospectively collected data
      on 295 patients who underwent either laparoscopic sleeve gastrectomy (256
      patients) or laparoscopic Roux-en-Y gastric bypass (39 patients) was performed.
      Body composition variables were measured with the analyzer, GAIA 359 PLUS, which
      included the parameters; total body weight, body mass index, excess weight, basal
      metabolic rate, fat-free mass, fat mass, and total body water. RESULTS: There
      were no statistical differences in gender, ethnicity, age, weight, height, and
      body mass index between laparoscopic sleeve gastrectomy and Roux-en-Y gastric
      bypass. At each time point (6, 12, 24, and 36 months) post-operation, there was
      no significant differences in % total body weight loss, basal metabolic rate, fat
      mass, fat percentage, and total body water between sleeve gastrectomy and bypass
      patients. There was significant difference (p < 0.05) in fat free mass only at 3
      years post-operation, with sleeve gastrectomy patients having 9.79 kg less fat
      free mass than bypass patients. However, after multivariate analysis, we found no
      statistically significant differences. CONCLUSION: Sleeve gastrectomy and gastric
      bypass seemed to give similar changes to body composition.

PMID- 30187325
TI  - Prognostic Ability of Central Lymph Node Metastasis for Gastric Cancer Deserves
      Additional Investigation.

PMID- 30187327
TI  - Can Perianal Fistula Be Treated Non-surgically with Platelet-Rich Fibrin Sealant?
AB  - INTRODUCTION: In the last 20 years, various procedures have been suggested for
      the treatment of anal fistula whilst minimising anal sphincter injury and
      preserving optimal function. Since 2011, patients at our hospital have been
      treated for anal fistula by means of platelet-rich fibrin plugs. To do so, three
      different application techniques have been used, the most recent of which is a
      non-surgical approach. In this paper, we compare and contrast the results
      obtained by each of these three techniques. MATERIAL AND METHOD: This study
      compares three procedures in which the anal fistula was sealed using platelet
      rich fibrin: for the patients in group A, the plug was surgically inserted, under
      anaesthesia, and traditional methods were used to curette the fistula tract and
      close the internal orifice; for those in group B, the plug was surgically
      inserted, under anaesthesia, after curettage of the fistula tract using a
      graduated set of cylindrical curettes, and the internal orifice was closed as
      before; and for those in group C, the plug was inserted during outpatient
      consultation, without anaesthesia, without curettage and without closure of the
      internal orifice. RESULTS: The patients in the three groups were homogeneous in
      terms of sex, age, ASA classification, location of the fistula and previous
      insertion of the seton. There were no significant differences in morbidity or
      postoperative continence. However, there was a statistically significant
      difference in the outcomes achieved, in favour of group B, while groups A and C
      obtained similar results. CONCLUSIONS: Outpatient treatment of perianal fistula
      is totally innocuous. It is a very low cost procedure and the results obtained
      are highly acceptable (similar to those of the surgical insertion of a plug, with
      traditional curettage). Therefore, we believe this approach should be considered
      a valid initial treatment for perianal fistula, reserving surgical treatment
      (curettage and sealing using a cylindrical-curette kit) for cases in which this
      initial method is unsuccessful. This would avoid many complications and achieve
      considerable financial savings for the health system.

PMID- 30187326
TI  - The Relationship Between Postoperative Chemotherapy and Remnant Liver
      Regeneration and Outcomes After Hepatectomy for Colorectal Liver Metastasis.
AB  - BACKGROUND: Postoperative chemotherapy for treating colorectal liver metastasis
      (CLM) has been introduced with the aim of improving therapeutic outcomes.
      However, there is no consensus on the utility of multidisciplinary treatments
      with postoperative chemotherapy. Therefore, we evaluated surgical outcomes in
      patients with CLMs who underwent hepatectomy, while focusing on the effects of
      post-hepatectomy chemotherapy on remnant liver regeneration. METHODS: Two hundred
      ninety patients who underwent hepatectomy were retrospectively analyzed using
      propensity score matching. Postoperative outcomes were evaluated with a focus on
      the effects of post-hepatectomy chemotherapy on regeneration of the remnant liver
      in patients with CLM. The remnant liver volumes (RLVs) were measured
      postoperatively using multi-detector computed tomography on day 7 and months 1,
      2, 5, and 12 after the operation. RESULTS: RLV regeneration and postoperative
      blood laboratory data did not differ significantly between patients who received
      postoperative chemotherapy and those who did not receive postoperative
      chemotherapy immediately after surgery or at any time point from postoperative
      day 7 to postoperative month 12. The recurrence rates, including same and other
      segmental intrahepatic recurrences, as well as the resection frequency of the
      remnant liver were not significantly different between the two groups.
      CONCLUSION: Postoperative chemotherapy may be of small significance for patients
      with CLM in terms of the remnant liver volume regeneration and functional
      recovery.

PMID- 30187329
TI  - Gallbladder Torsion: US, CT, and MRI Findings.

PMID- 30187328
TI  - Surgical Technique of Pancreatic Parenchyma Transection-Delayed Approach (PPTDA)
      in Hepatopancreatoduodenectomy for Hilar Cholangiocarcinoma.
AB  - BACKGROUND: The combination of major hepatectomy and pancreatoduodenectomy (PD),
      that is, a hepatopancreatoduodenectomy (HPD), is the only curative treatment for
      bile duct cancer with extensive horizontal tumor spread invading both the hepatic
      hilum and the intrapancreatic bile duct. However, this aggressive procedure
      remains controversial with regard to the balance between the survival benefit and
      high risk of mortality and morbidity, especially the risk for postoperative
      hepatic failure and postoperative pancreatic fistula. Here, we describe the
      efficacy of a novel modified technique of HPD with delayed division of the
      pancreatic parenchyma for hilar cholangiocarcinoma, and focus on the surgical
      technique and the short-term outcomes, with a representative case. TECHNICAL
      PRESENTATION: This new surgical technique involves dissection of the pancreatic
      parenchyma and relevant mesoduodenum at the final step after dissecting the
      required parts on the inferior side and superior side of the tumor, enabling
      excision of the resected specimen. This technique described herein can prevent
      saponification of the resected surface of the pancreas by dissecting the
      pancreatic parenchyma toward the latter half of the surgical procedure as much as
      possible. The results suggest that there may also be a relationship between this
      technique and the prevention of postoperative pancreatic fistula. CONCLUSION:
      This new surgical technique of HPD may be able to prevent postoperative
      pancreatic fistula by performing intraoperative dissection of the pancreatic
      parenchyma as late as possible, which in turn, may improve the safety of HPD.

PMID- 30187330
TI  - Pancreatic Actinomycosis.

PMID- 30187331
TI  - Dabigatran (Pradaxa) Is Safe for Extended Venous Thromboembolism Prophylaxis
      After Surgery for Pancreatic Cancer.
AB  - BACKGROUND: The American College of Chest Physicians and American Hepato
      Pancreato-Biliary Association recommend using low-molecular-weight heparin for 28
      days postoperatively for venous thromboembolism prophylaxis after cancer surgery.
      Dabigatran is a once daily oral anticoagulant that is FDA approved for venous
      thromboembolism prophylaxis after orthopedic surgery, uses fixed dosing, and has
      an antidote. METHODS: Patients undergoing surgery for malignant pancreatic tumors
      (neuroendocrine excluded) from January 2017 to January 2018 were converted to
      dabigatran 220 mg daily on discharge until postoperative day 28; patients with
      medical or insurance contraindications were converted to enoxaparin or another
      direct oral anticoagulant. The primary endpoint was bleeding complications
      through 90 days. RESULTS: A total of 134 patients were considered for this study
      (median age 67 +/- 10; 58.9% male). Eighty-seven (82.9%) patients received
      dabigatran and 18 (17.1%) received another form of anticoagulation. There were 19
      (4.2%) patients not prescribed dabigatran due to medical or inpatient
      contraindications. Four patients experienced bleeding complications after
      discharge while on dabigatran. Two (2%) were major bleeds (Clavien-Dindo IV and
      V), and 2 (2%) were minor (Clavien-Dindo I). Patient compliance was excellent,
      with 93% of prescribed patients fully completing their prophylaxis. There were 2
      patients that developed symptomatic deep vein thrombosis. CONCLUSION: The use of
      a direct oral anticoagulant as extended venous thromboembolism prophylaxis after
      major gastrointestinal surgery has not been studied to date. These results show
      dabigatran to be a safe alternative to low-molecular-weight heparin for extended
      venous thromboembolism prophylaxis with regard to bleeding complications.

PMID- 30187332
TI  - Lymph Node Ratio in Pancreatic Adenocarcinoma After Preoperative Chemotherapy vs.
      Preoperative Chemoradiation and Its Utility in Decisions About Postoperative
      Chemotherapy.
AB  - BACKGROUND: Single-center studies in pancreatic adenocarcinoma have suggested
      that preoperative chemotherapy (PCT) is associated with higher lymph node ratio
      (LNR) than preoperative chemoradiation (PCRT). The association of postoperative
      chemotherapy with overall survival (OS) in patients treated with PCT and PCRT
      remains unclear. Our objectives were to investigate whether (1) PCT is associated
      with higher LNR than PCRT and (2) postoperative chemotherapy is associated with
      longer OS after PCT and PCRT in LNR-stratified cohorts. METHODS: A retrospective
      cohort study was performed of patients with pancreatic adenocarcinoma treated
      with PCT or PCRT followed by resection between 2006 and 2014 in the National
      Cancer Database. Temporal trends were evaluated with Cuzick's test. OS was
      evaluated with multivariable Cox regression and inverse probability weighted
      (IPW) Cox regression. RESULTS: Of 4187 patients, 1993 (47.6%) received PCT. PCT
      rates were stable at approximately 30% in 2006-2010 (p = 0.33) but increased to
      64.9% by 2014 (p < 0.001). Node positivity rates were higher after PCT than PCRT
      (62.7 vs. 41.8%, P < 0.001) and mean LNR was higher (0.10 [95% CI 0.096, 0.11]
      vs. 0.058 [95% CI 0.052, 0.063], P < 0.001). Postoperative chemotherapy was
      associated with longer OS in patients with LNR 0.01-0.149 after PCT by univariate
      analysis (median OS 34.5 vs. 26.5 months, P = 0.002), multivariable Cox
      regression (HR 0.64, 95% CI 0.48, 0.84), and IPW Cox regression (HR 0.72, 95% CI
      0.55, 0.94). Postoperative chemotherapy was not associated with longer OS for
      patients who were node-negative or who had LNR >= 0.15 after PCT or for any
      patient subgroups after PCRT. CONCLUSIONS: PCT is associated with a higher LNR
      and higher rates of node positivity than PCRT. Postoperative chemotherapy is
      associated with longer OS than observation in patients with a LNR of 0.01-0.149
      after PCT.

PMID- 30187333
TI  - Laparoscopic Ultrasonography Versus Magnetic Resonance Cholangiopancreatography
      in Laparoscopic Surgery for Symptomatic Cholelithiasis and Suspected Common Bile
      Duct Stones.
AB  - BACKGROUND: There continues to be controversy regarding the optimal screening
      modality in patients with symptomatic cholelithiasis and suspected common bile
      duct (CBD) stones. The aim of this study was to assess the diagnostic accuracy of
      laparoscopic ultrasonography (LUS) compared to magnetic resonance
      cholangiopancreatography (MRCP). METHODS: Both LUS and MRCP were performed to
      evaluate the CBD stones and biliary anatomy in 200 patients undergoing
      laparoscopic surgery. Pre-, intra-, and postoperative data were collected
      prospectively and reviewed retrospectively. RESULTS: Coexisting CBD stones were
      identified in 64 of 200 (32%) patients by surgical exploration or postoperative
      ERCP. For the detection of CBD stones, LUS yielded a positive predictive value of
      100%, a negative predictive value of 99.3%, a sensitivity of 98.4%, and a
      specificity of 100%. Preoperative MRCP had a positive predictive value of 87.9%,
      a negative predictive value of 95.5%, a sensitivity of 90.6%, and a specificity
      of 94.1%. The non-random concordance between MRCP and LUS was considered to be
      excellent with a kappa coefficient of 0.92 (p < 0.01). CONCLUSIONS: LUS can
      reduce the need for MRCP examination and can become the primary imaging method
      for the evaluation of CBD stones in laparoscopic surgery.

PMID- 30187334
TI  - Influence of Conversion and Anastomotic Leakage on Survival in Rectal Cancer
      Surgery; Retrospective Cross-sectional Study.
AB  - BACKGROUND: Conversion and anastomotic leakage in colorectal cancer surgery have
      been suggested to have a negative impact on long-term oncologic outcomes. The aim
      of this study in a large Dutch national cohort was to analyze the influence of
      conversion and anastomotic leakage on long-term oncologic outcome in rectal
      cancer surgery. METHODS: Patients were selected from a retrospective cross
      sectional snapshot study. Patients with a benign lesion, distant metastasis, or
      unknown tumor or metastasis status were excluded. Overall (OS) and disease-free
      survival (DFS) were compared between laparoscopic, converted, and open surgery as
      well as between patients with and without anastomotic leakage. RESULTS: Out of a
      database of 2095 patients, 638 patients were eligible for inclusion in the
      laparoscopic, 752 in the open, and 107 in the conversion group. A total of 746
      patients met the inclusion criteria and underwent low anterior resection with
      primary anastomosis, including 106 (14.2%) with anastomotic leakage. OS and DFS
      were significantly shorter in the conversion compared to the laparoscopic group
      (p = 0.025 and p = 0.001, respectively) as well as in anastomotic leakage
      compared to patients without anastomotic leakage (p = 0.002 and p = 0.024,
      respectively). In multivariable analysis, anastomotic leakage was an independent
      predictor of OS (hazard ratio 2.167, 95% confidence interval 1.322-3.551) and DFS
      (1.592, 1077-2.353). Conversion was an independent predictor of DFS (1.525, 1.071
      2.172), but not of OS. CONCLUSION: Technical difficulties during laparoscopic
      rectal cancer surgery, as reflected by conversion, as well as anastomotic leakage
      have a negative prognostic impact, underlining the need to improve both aspects
      in rectal cancer surgery.

PMID- 30187335
TI  - The Safety and Feasibility of Single-Port Laparoscopic Gastrectomy for Advanced
      Gastric Cancer.
AB  - BACKGROUND: Single-port laparoscopic surgery maximizes the advantages of
      laparoscopic surgery by reducing damage of the abdominal wall. However, no
      comparative studies have addressed its application to gastrectomy for advanced
      gastric cancer (AGC). We therefore aimed to demonstrate the safety and
      feasibility of single-port laparoscopic gastrectomy (SLG) for the treatment of
      AGC by comparing it with conventional multi-port laparoscopic gastrectomy (MLG).
      METHODS: We searched the prospective gastric cancer database of our institute for
      patients with AGC who underwent SLG or MLG between October 2007 and December
      2013. Cases of R2 resection with distant metastasis or concurrent surgery for
      comorbid malignant lesions were excluded. One-to-one propensity score matching
      was performed to reduce bias from confounding patient-related variables, and the
      short- and long-term outcomes were compared between the two groups. RESULTS: We
      identified 216 patients who underwent SLG (n = 100) or MLG (n = 116). After
      propensity score matching, we selected 73 pairs of patients who underwent SLG
      (distal gastrectomy, 49; total gastrectomy, 24) or MLG (distal gastrectomy, 45;
      total gastrectomy, 28). While the mean operative times were comparable between
      the groups, the SLG group had less blood loss, a lower postoperative morbidity,
      and shorter postoperative hospital stays. The 5-year survival rates were 74.2% in
      the SLG group and 60.2% in the MLG group (P = 0.081 by log-rank test).
      CONCLUSIONS: SLG is shown to be safe and feasible for the treatment of AGC, with
      better short-term results and acceptable oncologic outcomes and may be applicable
      for AGC treatment.

PMID- 30187336
TI  - Prognostic Implication of Negative Lymph Node Count in ypN+ Rectal Cancer after
      Neoadjuvant Chemoradiotherapy and Construction of a Prediction Nomogram.
AB  - PURPOSE: This study aimed to investigate the prognostic significance of negative
      lymph nodes (NLNs) for ypN+ rectal cancer after neoadjuvant chemoradiotherapy
      (nCRT) and radical surgery and to construct a nomogram predicting disease-free
      survival (DFS). METHOD: One hundred fifty-eight eligible patients were included.
      X-tile analysis was performed to determine cutoff values of NLNs.
      Clinicopathological and survival outcomes were compared. A Cox regression
      analysis was performed to identify prognostic factors of DFS. A nomogram was
      constructed and validated internally. RESULTS: X-tile analysis identified cutoff
      values of 4 and 16 in terms of DFS (chi2 = 8.129, p = 0.017). The 3-year DFS
      rates for low (<= 4), middle (5-16), and high (>= 17) NLNs group was 15.2, 55.5,
      and 73.1%, respectively (P = 0.017). NLN count (NLNs >= 17, HR = 0.400, P =
      0.022), IMA nodal metastasis (HR = 1.944, P = 0.025), tumor differentiation
      (poor/anaplastic, HR = 1.805, P = 0.021), and ypT4 stage (HR = 7.787, P = 0.047)
      were independent prognostic factors of DFS. A predicting nomogram incorporating
      the four significant predictors was developed with a C-index of 0.64. CONCLUSION:
      NLN count was an independent prognostic factor of DFS in patients with ypN+
      rectal cancer following nCRT. A nomogram incorporating NLN count, IMA nodal
      metastasis, tumor differentiation, and ypT stage could stratify rectal cancer
      patients with different DFS and might be helpful during clinical decision-making.

PMID- 30187337
TI  - Lung-Resident Mesenchymal Stem Cells Promote Repair of LPS-Induced Acute Lung
      Injury via Regulating the Balance of Regulatory T cells and Th17 cells.
AB  - Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are
      associated with high morbidity and mortality. Mesenchymal stem cells (MSCs) have
      been shown to improve ALI, and the imbalance of regulatory T cells (Tregs) and
      Th17 cells is associated with mortality in ALI/ARDS patients. However, whether
      administration of lung-resident MSC (LRMSC) improves lung injury and regulates
      the balance of Tregs and Th17 cells remains unknown. An ALI animal model was
      induced by LPS, and PBS or LRMSC were administered via tail vein after 4 h. LRMSC
      were subsequently detected in the lungs by a live imaging system (Berthold LB983,
      Germany). Lung morphology; lung wet-to-dry weight ratio; and total protein
      concentration, inflammatory cells, and cytokines in bronchoalveolar lavage fluid
      (BALF) and plasma were determined. The percentage of Tregs in lung and spleen,
      and of Th17 cells in lung and blood, were also evaluated. The results showed that
      LRMSC not only attenuated histopathological damage but also mediated the
      downregulation of lung wet-to-dry weight ratio and the reduction of total protein
      concentration and inflammatory cells in BALF. LRMSC also decreased inflammatory
      cytokines in both BALF and plasma and increased KGF-2 and surfactant protein C
      (SPC) expression in the lung. Flow cytometry revealed the upregulation of Tregs
      and the downregulation of Th17 cells, and the increase in the ratio of Tregs and
      Th17 cells. The live imaging system showed that LRMSC migrated to and were
      retained in the injured area. In conclusion, the results indicated that
      administration of LRMSC attenuates LPS-induced ALI via upregulating the balance
      of Tregs and Th17 cells.

PMID- 30187338
TI  - Progranulin Promotes Regeneration of Inflammatory Periodontal Bone Defect in Rats
      via Anti-inflammation, Osteoclastogenic Inhibition, and Osteogenic Promotion.
AB  - Progranulin (PGRN) has been proved to play a crucial role in anti-inflammation
      and osteogenesis promotion; thus, it was hypothesized that PGRN could promote
      bone regeneration in periodontal disease. In this experiment, the periodontal
      bone defects were established in periodontitis rats; recombinant human
      progranulin (rhPGRN), tumor necrosis factor alpha inhibitor (anti-TNF-alpha), or
      phosphate buffer saline (PBS)-loaded collagen membrane scaffolds were implanted
      within defects and the rats were sacrificed at scheduled time points. Volume of
      new bone was assessed by radiological and histomorphometric analyses. Expression
      of osteogenesis-related markers and tumor necrosis factor-alpha (TNF-alpha) was
      evaluated using immunohistochemistry. Tartrate-resistant acid phosphatase (TRAP)
      staining was also performed to determine the number of osteoclasts.
      Immunofluorescence (IF) staining was performed to explore the interaction between
      rhPGRN and tumor necrosis factor receptors (TNFRs). The results showed that the
      rhPGRN group had significantly superior quantity and quality of newly formed
      bone, higher expression of alkaline phosphatase (ALP), runt-related transcription
      factor 2 (Runx2), and TNFR2 compared with the PBS group and the anti-TNF-alpha
      group. Similarly to the anti-TNF-alpha group, the rhPGRN group also exhibited the
      significant inhibitory effect on the expression of TNF-alpha and the number of
      TRAP-positive cells compared with the PBS group. Hence, our experiment suggests
      that PGRN promotes regeneration of inflammatory periodontal bone defect in rats
      via anti-inflammation, osteoclastogenic inhibition, and osteogenic promotion.
      Local administration of PGRN may provide a new therapeutic strategy for
      periodontal bone regeneration.

PMID- 30187339
TI  - CDK5 Regulates PD-L1 Expression and Cell Maturation in Dendritic Cells of CRSwNP.
AB  - The maturation of dendritic cells is critical for chronic rhinosinusitis with
      nasal polyps (CRSwNPs), especially eosinophilic chronic rhinosinusitis with nasal
      polyps (EosCRSwNPs), but the regulation mechanism of dendritic cells (DCs)
      maturation is still unclear. We identified nasal mucosa of 20 patients with
      EosCRSwNP, 16 non-EosCRSwNP patients, and inferior turbinate of 14 patients with
      nasal septum deviation after surgery. The expression of cyclin-dependent kinase 5
      (CDK5) and programmed cell death 1 ligand 1 (PD-L1) were detected by
      immunofluorescent, real-time quantitative PCR, and Western blot in EosCRSwNP. The
      level of dendritic cell maturation was detected by flow cytometry and
      immunofluorescence staining after CDK5 expression interference with small
      interfering RNA (siRNA). The expression of CDK5 and PD-L1 in EosCRSwNP nasal
      mucosal tissue was significantly higher than that of non-EosCRSwNP and inferior
      turbinate nasal mucosa tissue, and there was a positive correlation between them.
      Immunofluorescence staining showed that CDK5 and PD-L1 were co-localized in
      dendritic cells. Synergistic stimulation of dendritic cells with LPS and TNF
      alpha promotes the maturation of dendritic cells and increases the expression of
      CDK5 and PD-L1. However, blocking the expression of CDK5 in dendritic cells with
      siRNAs leads to a blockage of cell maturation. CDK5 can regulate the expression
      of PD-L1, and its presence is critical for the maturation of dendritic cells.
      CDK5 may play an important role in the pathogenesis of CRSwNP disease.

PMID- 30187340
TI  - Telocytes in the mouse testicular interstitium: implications of G-protein-coupled
      estrogen receptor (GPER) and estrogen-related receptor (ERR) in the regulation of
      mouse testicular interstitial cells.
AB  - Telocytes (TCs), a novel type of interstitial cells, are involved in tissue
      homeostasis maintenance. This study aimed to investigate TC presence in the
      interstitium of mouse testis. Additionally, inactivation of the G-coupled
      membrane estrogen receptor (GPER) in the testis was performed to obtain insight
      into TC function, regulation, and interaction with other interstitial cells. Mice
      were injected with a GPER antagonist (G-15; 50 MUg/kg bw), and the GPER-signaling
      effect on TC distribution, ultrastructure, and function, as well as the
      interstitial tissue interaction of GPER with estrogen-related receptors (ERRs),
      was examined. Microscopic observations of TC morphology were performed with the
      use of scanning and transmission electron microscopes. Telocyte functional
      markers (CD34; c-kit; platelet-derived growth factor receptors alpha and beta,
      PDGFRalpha and beta; vascular endothelial growth factor, VEGF; and vimentin) were
      analyzed by immunohistochemistry/immunofluorescence and Western blot. mRNA
      expression of CD34 as well as ERR alpha, beta, and gamma was measured by qRT-PCR.
      Relaxin and Ca2+ concentrations were analyzed by immunoenzymatic and colorimetric
      assays, respectively. For the first time, we reveal the presence of TCs in the
      interstitium together with the peritubular area of mouse testis. Telocytes were
      characterized by specific features such as a small cell body and extremely long
      prolongations, constituting a three-dimensional network mainly around the
      interstitial cells. Expression of all TC protein markers was confirmed. Based on
      scanning electron microscopic observation in GPER-blocked testis, groups of TCs
      were frequently seen. No changes were found in TC ultrastructure in GPER-blocked
      testis when compared to the control. However, tendency to TC number change
      (increase) after the blockage was observed. Concomitantly, no changes in mRNA
      CD34 expression and increase in ERR expression were detected in GPER-blocked
      testes. In addition, Ca2+ was unchanged; however, an increase in relaxin
      concentration was observed. Telocytes are an important component of the mouse
      testicular interstitium, possibly taking part in maintaining its microenvironment
      as well as contractile and secretory functions (via themselves or via controlling
      of other interstitial cells). These cells should be considered a unique and
      useful target cell type for the prevention and treatment of testicular
      interstitial tissue disorders based on estrogen-signaling disturbances.

PMID- 30187341
TI  - Virus-induced gene silencing (VIGS) for functional analysis of MYB80 gene
      involved in Solanum lycopersicum cold tolerance.
AB  - Virus-induced gene silencing (VIGS) is a method for transiently silencing genes
      in dicot and monocot plants. To evaluate the effects of chilling injury on
      activity of the MYB80 gene in Solanum lycopersicum, an investigation was
      conducted by VIGS using TRV-GFP (a modified TRV vector) to silence the target
      gene. During the chilling treatment (4/12  degrees C, 8/16-h dark/light
      photoperiod, with 60% humidity), the leaves were collected to analyze the
      malondialdehyde (MDA) content, soluble sugar content, free proline levels, and
      relative electric conductivity (REC). Leaves collected 2 weeks after chilling
      treatment were used to detect the in situ accumulation of superoxide radical (O2
      ). Additionally, we collected leaves at selected time points for semi
      quantitative reverse transcription-PCR (RT-PCR) analysis. Eventually, 20 days
      after chilling treatment, all plants were evaluated at 4  degrees C for 7 days to
      assess the chilling injury index. The results validated that the MYB80 gene was
      related to cold tolerance of tomato plants, and that silencing of the MYB80 gene
      reduced the cold resistance ability.

PMID- 30187343
TI  - Nanofibrous Scaffolds with Biomimetic Composition for Skin Regeneration.
AB  - Treatments of skin injuries caused by trauma and diseases are among the most
      considerable medical problems. The use of scaffolds that can cover the wound area
      and support cellular ingrowth has shown great promise. However, mimicking the
      physicochemical properties of the native skin extracellular matrix (ECM) is
      essential for the successful integration of these scaffolds. Elastin has been
      known as the second main protein-based component of the native skin ECM. In this
      research, scaffolds containing gelatin, cellulose acetate, and elastin were
      fabricated using electrospinning. Subsequently, the effects of soluble elastin on
      the physical, mechanical, and biological properties of the prepared scaffolds
      were studied. The results confirmed that the presence of elastin in the
      composition changed the fiber morphology from straight to ribbon-like structure
      and decreased the swelling ratio and degradation rate of the scaffold. In vitro
      experiments showed that elastin-containing scaffolds supported the attachment and
      proliferation of fibroblast cells. Overall, the obtained results suggest the
      ternary blend of gelatin, cellulose acetate, and elastin as a good candidate for
      skin tissue engineering.

PMID- 30187342
TI  - Arabidopsis tonoplast intrinsic protein and vacuolar H+-adenosinetriphosphatase
      reflect vacuole dynamics during development of syncytia induced by the beet cyst
      nematode Heterodera schachtii.
AB  - Plant parasitic cyst nematodes induce specific hypermetabolic syncytial nurse
      cell structures in host roots. A characteristic feature of syncytia is the lack
      of the central vacuole and the formation of numerous small and larger vesicles.
      We show that these structures are formed de novo via widening of ER cisternae
      during the entire development of syncytium, whereas in advanced stages of
      syncytium development, larger vacuoles are also formed via fusion of
      vesicles/tubules surrounding organelle-free pre-vacuole regions. Immunogold
      transmission electron microscopy of syncytia localised the vacuolar markers E
      subunit of vacuolar H+-adenosinetriphosphatase (V-ATPase) complex and tonoplast
      intrinsic protein (gamma-TIP1;1) mostly in membranes surrounding syncytial
      vesicles, thus indicating that these structures are vacuoles and that some of
      them have a lytic character. To study the function of syncytial vacuoles, changes
      in expression of AtVHA-B1, AtVHA-B2 and AtVHA-B3 (coding for isoforms of subunit
      B of V-ATPase), and TIP1;1 and TIP1;2 (coding for gamma-TIP proteins) genes were
      analysed. RT-qPCR revealed significant downregulation of AtVHA-B2, TIP1;1 and
      TIP1;2 at the examined stages of syncytium development compared to uninfected
      roots. Expression of VHA-B1 and VHA-B3 decreased at 3 dpi but reached the level
      of control at 7 dpi. These results were confirmed for TIP1;1 by monitoring At
      gamma-TIP-YFP reporter construct expression. Infection test conducted on tip1;1
      mutant plants showed formation of larger syncytia and higher numbers of females
      in comparison to wild-type plants indicating that reduced levels or lack of
      TIP1;1 protein promote nematode development.

PMID- 30187344
TI  - Identifying hQC Inhibitors of Alzheimer's Disease by Effective Customized
      Pharmacophore-Based Virtual Screening, Molecular Dynamic Simulation, and Binding
      Free Energy Analysis.
AB  - Human glutaminyl cyclase (hQC) appeared as a promising new target with its
      inhibitors attracted much attention for the treatment of Alzheimer's disease (AD)
      in recent years. But so far, only a few compounds have been reported as hQC
      inhibitors. To find novel and potent hQC inhibitors, a high-specificity ZBG (zinc
      binding groups)-based pharmacophore model comprising customized ZBG feature was
      first generated using HipHop algorithm in Discovery Studio software for screening
      out hQC inhibitors from the SPECS database. After purification by docking studies
      and drug-like ADMET properties filters, four potential hit compounds were
      retrieved. Subsequently, these hit compounds were subjected to 30-ns molecular
      dynamic (MD) simulations to explore their binding modes at the active side of
      hQC. MD simulations demonstrated that these hit compounds formed a chelating
      interaction with the zinc ion, which was consistent with the finding that the
      electrostatic interaction was the major driving force for binding to hQC
      confirmed with MMPBSA energy decomposition. Higher binding affinities of these
      compounds were also verified by the binding free energy calculations comparing
      with the references. Thus, these identified compounds might be potential hQC
      candidates and could be used for further investigation.

PMID- 30187345
TI  - A Multi-Center, Open-Label, Two-Arm Parallel Group Non-inferiority Randomized
      Controlled Trial Evaluating the Effect of Pitavastatin, Compared to Atorvastatin,
      on Glucose Metabolism in Prediabetics with Hypertension and Dyslipidemia:
      Rationale and Design for the China Hemoglobin A1c Metabolism Protection Union
      Study (CAMPUS).
AB  - BACKGROUND: Hypertension and dyslipidemia are major risk factors for
      cardiovascular disease (CVD). In 2012, over 270 million patients (25.2%) in China
      were hypertensive and 40.4% was dyslipidemic. The majority of these patients rely
      on statins for the prevention of cardiovascular disease. However, certain types
      of statins (e.g., atorvastatin), compared to others (e.g., pitavastatin), may be
      associated with unfavorable effects on glucose metabolism. This leads to concerns
      when prescribing statins to patients who also have a predisposition to glucose
      metabolic disorders (i.e., prediabetes). Thus, this study aims to investigate the
      effect of pitavastatin, compared to atorvastatin, on glucose metabolism, as
      measured by hemoglobin A1c (HbA1c), in Chinese prediabetics with hypertension and
      dyslipidemias. METHODS: The China hemoglobin A1c Metabolism Protection Union
      Study (CAMPUS) is a multi-center, prospective, open-label, 12-month, two-arm
      parallel group, and non-inferiority randomized controlled trial (RCT). A total of
      396 prediabetics with hypertension and dyslipidemias will be randomly assigned
      1:1 to either pitavastatin 2 mg/day or atorvastatin 20 mg/day, and followed for
      12 months (follow-up visits at 1, 3, 6, and 12 months) for HbA1c levels, as well
      as other measures of glucose metabolism, serum lipid levels, blood pressure
      control, measures of inflammation, vascular endothelial function, carotid
      atherosclerosis, and hypertension-related left ventricular hypertrophy. If the
      results of low-density lipoprotein cholesterol (LDL-C) levels in month 3 after
      treatment initiation do not meet individual target, drug dose for the participant
      would be doubled. DISCUSSION: CAMPUS will be the first RCT to investigate the
      effect of pitavastatin, compared to atorvastatin, on glucose metabolism in
      Chinese prediabetics with hypertension and dyslipidemias. Further, this study
      might eventually provide information to design a clinical strategy, and
      facilitate the improvement of primary prevention in patients at risk for diabetes
      and CVD. TRIAL REGISTRATION: ClinicalTrials.gov number: NCT03532620. Registered
      22 May 2018.

PMID- 30187346
TI  - Heart Failure with Preserved Ejection Fraction Trials Have Heterogeneous Control
      Groups: a Comparison of Kaplan-Meier Curves.
AB  - PURPOSE: Previous studies have evaluated intra-study heterogeneities of heart
      failure with preserved ejection fraction (HFpEF), but inter-study heterogeneities
      remain poorly understood. We investigate the heterogeneities of outcomes among
      control groups of HFpEF trials. METHODS: We included randomized controlled trials
      recruiting HFpEF patients with ejection fraction >= 40% and reporting Kaplan
      Meier curves for at least 36 months. The Kaplan-Meier curves of control groups
      were extracted and calculated for hazard ratios and 95% confidence intervals. Two
      virtual trials were developed to validate the reliability and accuracy of our
      method. RESULTS: Of 4161 studies, we included six trials containing 7682 HFpEF
      patients in control groups. The DIG trial had the highest all-cause mortality,
      cardiovascular mortality, heart failure mortality, and composite endpoints of
      cardiovascular mortality and heart failure hospitalization (all p < 0.001). The
      TOPCAT trial had the lowest all-cause mortality, cardiovascular mortality, heart
      failure hospitalization, and composite of cardiovascular mortality and heart
      failure hospitalization (all p < 0.001). Adoption of different ejection fraction
      cut-off values for HFpEF diagnosis did not significantly change the outcomes of
      control groups in the DIG trial (45% vs. 50%: hazard ratio, 1.05, 95% confidence
      interval, 0.97-1.13, p = 0.271), or in the CHARM-Preserved trial (40% vs. 50%:
      hazard ratio, 1.01, 95% confidence interval, 0.93-1.09, p = 0.864) during 36
      month follow-up. CONCLUSIONS: The control groups of HFpEF trials have
      heterogeneous outcomes. Future trials should consider these heterogeneities when
      designing protocols.

PMID- 30187347
TI  - A Narrative Review on Thrombolytics in Advanced CKD: Is it an Evidence-Based
      Therapy?
AB  - PURPOSE: A timely pharmacoinvasive strategy consisting of thrombolytic therapy
      (TT) plays a pivotal role in three major scenarios: acute ischemic stroke (AIS),
      acute myocardial infarction (STEMI), and massive pulmonary embolism (PE).
      Presence of advanced chronic kidney disease (CKD) (estimated glomerular
      filtration rate < 30 mL/min/1.73 m2), known to disturb thrombotic/thrombolytic
      equilibrium, causes difficulties for clinicians in evaluating risk-benefit
      balance, as current guidelines do not address the relationship between TT and the
      advanced CKD. This narrative review aims to evaluate the most important
      scientific resources regarding the evidences, benefits, and risks of using
      thrombolytics in advanced CKD. METHODS: We searched the electronic database of
      PubMed for studies evaluating the relationship between renal dysfunction and TT
      in patients with STEMI, AIS, and massive PE. Randomized controlled trials (RCTs),
      observational studies including prospective or retrospective cohort studies,
      reviews, meta-analyses, and guidelines were included if referring to TT for one
      of the three scenarios in advanced CKD. RESULTS: Prothrombotic conditions in CKD,
      associated with an increased risk of hemorrhages, can affect the safety and
      efficacy of TT. Concerns regarding in-hospital bleeding events and poor clinical
      outcomes subsequent to TT in advanced CKD continue to cause underutilization or
      delaying routine reperfusion therapy. CONCLUSIONS: The impact of TT on the
      outcomes of advanced CKD patients is poorly understood to date, with scarce data
      available in current guidelines and conflicting results from observational
      studies. Until evidence-based data from RCTs will be obtained, the clinical
      challenge of maximizing benefits for this high-risk subgroup lays in the hands of
      practicing clinicians.

PMID- 30187349
TI  - The Ninth American Conference on Pharmacometrics (ACoP9).

PMID- 30187348
TI  - Historical Evolution of the Polymorphous Adenocarcinoma.
AB  - The 2017 World Health Organization Classification of Head and Neck Tumors
      introduced for the first time the diagnostic terminology "cribriform variant of
      polymorphous adenocarcinoma". This nomenclature attempts to reconciliate the
      ongoing taxonomical controversy related to cribriform adenocarcinoma of tongue.
      In order to better understand this classification conundrum, it is imperative for
      pathologist to comprehend the historical evolution of polymorphous adenocarcinoma
      formerly known as polymorphous "low grade" adenocarcinoma. This review highlights
      our understanding of these tumors since their origins.

PMID- 30187350
TI  - A microfluidic device with spatiotemporal wall shear stress and ATP signals to
      investigate the intracellular calcium dynamics in vascular endothelial cells.
AB  - Intracellular calcium dynamics plays an important role in the regulation of
      vascular endothelial cellular functions. In order to probe the intracellular
      calcium dynamic response under synergistic effect of wall shear stress (WSS) and
      adenosine triphosphate (ATP) signals, a novel microfluidic device, which provides
      the adherent vascular endothelial cells (VECs) on the bottom of microchannel with
      WSS signal alone, ATP signal alone, and different combinations of WSS and ATP
      signals, is proposed based upon the principles of fluid mechanics and mass
      transfer. The spatiotemporal profiles of extracellular ATP signals from numerical
      simulation and experiment studies validate the implementation of our design. The
      intracellular calcium dynamics of VECs in response to either WSS signal or ATP
      signal alone, and different combinations of WSS and ATP signals have been
      investigated. It is found that the synergistic effect of the WSS and ATP signals
      plays a more significant role in the signal transduction of VECs rather than that
      from either WSS signal or ATP signal alone. In particular, under the combined
      stimuli of WSS and ATP signals with different amplitudes and frequencies, the
      amplitudes and frequencies of the intracellular Ca2+ dynamic signals are observed
      to be closely related to the amplitudes and frequencies of WSS or ATP signals.

PMID- 30187351
TI  - Correction to: Comparison of healing of full-thickness skin wounds grafted with
      multidirectional or unidirectional autologous artificial dermis: differential
      delivery of healing biomarkers.
AB  - In the original article text presenting and discussing results shown in Fig. 6
      omitted to mention that quantification of TGF-beta2 and TGF-beta3 was not
      included in Fig. 6a, c, e.

PMID- 30187352
TI  - Effect of supersaturation on the oral bioavailability of paclitaxel/polymer
      amorphous solid dispersion.
AB  - The aim of the present investigation was to evaluate the effect of
      supersaturation on the oral absorption of paclitaxel (PTX) in vivo. To achieve
      this, a PTX amorphous solid dispersion (ASD) was prepared by the solvent cast
      method. Among the enteric polymers tested, hypromellose acetate succinate
      (HPMCAS) MF was found to be the most suitable polymer for maintaining PTX
      supersaturation and inhibiting crystallization in vitro. The dissolution rate and
      extent of the ASD was remarkably improved compared with a physical mixture (PM)
      of PTX, HPMCAS-MF, and Poloxamer 188 (F68), reaching an apparent drug
      concentration of 25-30 MUg/mL and maintaining it for more than 2 h. The liquid
      liquid phase separation (LLPS) concentration of PTX in the presence of HPMCAS-MF
      was determined to be 23 MUg/mL, which was different to that of 40 MUg/mL in the
      absence of polymer. It indicated that HPMCAS was substantially incorporated into
      the drug-rich phase. Also, HPMCAS could absorb to the PTX surface and provided an
      interfacial barrier for crystal growth, as well as retard the incorporation of
      PTX from solution into the growing crystal lattice. The results of X-ray
      diffraction, differential scanning calorimetry analysis, and transmission
      electron microscopy confirmed that PTX existed in the amorphous state in the
      solid dispersion. Compared with the PM group, the ASD prepared with HPMCAS-MF and
      F68 achieved a 1.78-fold increase in relative oral bioavailability, while PTX
      solution yielded a 1.56-fold increase, which could be explained that the
      solubility and the permeability of PTX were not increased simultaneously through
      supersaturation in vivo. Likely, it was because Cremophor inhibited P
      glycoprotein in the intestine to some extent and maintained PTX at a higher
      concentration for a longer time.

PMID- 30187353
TI  - Influence of PEG coating on the biodistribution and tumor accumulation of pH
      sensitive liposomes.
AB  - Liposomes are lipid vesicles widely used as nanocarriers in targeted drug
      delivery systems for therapeutic and/or diagnostic purposes. A strategy to
      prolong the blood circulation time of the liposomes includes the addition of a
      hydrophilic polymer polyethylene glycol (PEG) moiety onto the surface of the
      vesicle. Several studies claim that liposome PEGylation by a single chain length
      or a combination of PEG with different chain lengths may alter the liposomes'
      pharmacokinetic properties. Therefore, the purpose of this study was to evaluate
      the influence of PEG on the biodistribution of pH-sensitive liposomes in a tumor
      bearing animal model. Three liposomal formulations (PEGylated or not) were
      prepared and validated to have a similar mean diameter, monodisperse
      distribution, and neutral zeta potential. The pharmacokinetic properties of each
      liposome were evaluated in healthy animals, while the biodistribution and
      scintigraphic images were evaluated in tumor-bearing mice. High tumor-to-muscle
      ratios were not statistically different between the PEGylated and non-PEGylated
      liposomes. While PEGylation is a well-established strategy for increasing the
      blood circulation of nanostructures, in our study, the use of polymer coating did
      not result in a better in vivo profile. Further studies must be carried out to
      confirm the feasibility of the non-PEGylated pH-sensitive liposomes for tumor
      treatment.

PMID- 30187354
TI  - Correction to: Meropenem/Vaborbactam: A Review in Complicated Urinary Tract
      Infections.
AB  - The article Meropenem/Vaborbactam: A Review in Complicated Urinary Tract
      Infections.

PMID- 30187355
TI  - Immune Checkpoint Inhibitors: Toward New Paradigms in Renal Cell Carcinoma.
AB  - Immune modulatory treatment regimens, led by immune checkpoint inhibitors, have
      transformed the treatment of clear-cell renal cell carcinoma. First-in-class, the
      PD-1 inhibitor nivolumab improved overall survival in advanced renal cell
      carcinoma following prior anti-angiogenic therapy, an important shift in the
      management of clear-cell renal cell carcinoma. Further improvements of long-term
      outcomes will be driven by combinations in the first-line setting, including PD
      1/PD-L1 associated with antiangiogenic therapies, or PD1/PD-L1 inhibitors with
      other immune checkpoint inhibitors such as anti-CTLA-4, anti-LAG-3 or TIM-3
      targeted therapies. The first two randomized Phase 3 trials assessing these
      combinations have now challenged sunitinib in first-line setting. First, the
      CheckMate 214 trial demonstrated an objective response rate and overall survival
      benefit for the combination of nivolumab plus ipilimumab in the intermediate- and
      poor-risk patients. Second, the IMMotion 151 study demonstrated a progression
      free survival benefit for the atezolizumab plus bevacizumab combination by
      investigator assessment. Further Phase 3 trials are awaited with tyrosine kinase
      and immune checkpoint inhibitor combinations. Clinical trials of immune
      checkpoint inhibitors are also actively investigated in the localized adjuvant or
      neoadjuvant setting. Nevertheless, the search for biomarkers along with new
      clinical trial designs will be crucial to better select the patients that may
      derive the greatest benefit from these advances. The continuing improvement of
      antitumor immunity comprehension and the emergence of new immune modulatory
      treatments will deeply change the management of renal cell carcinoma for the
      years to come.

PMID- 30187356
TI  - Enhancement by Nano-Diamino-Tetrac of Antiproliferative Action of Gefitinib on
      Colorectal Cancer Cells: Mediation by EGFR Sialylation and PI3K Activation.
AB  - Drug resistance complicates the clinical use of gefitinib. Tetraiodothyroacetic
      acid (tetrac) and nano-diamino-tetrac (NDAT) have been shown in vitro and in
      xenografts to have antiproliferative/angiogenic properties and to potentiate
      antiproliferative activity of other anticancer agents. In the current study, we
      investigated the effects of NDAT on the anticancer activities of gefitinib in
      human colorectal cancer cells. beta-Galactoside alpha-2,6-sialyltransferase 1
      (ST6Gal1) catalyzes EGFR sialylation that is associated with gefitinib resistance
      in colorectal cancers, and this was also investigated. Gefitinib inhibited cell
      proliferation of HT-29 cells (K-ras wild-type), and NDAT significantly enhanced
      the antiproliferative action of gefitinib. Gefitinib inhibited cell proliferation
      of HCT116 cells (K-ras mutant) only in high concentration, and this was further
      enhanced by NDAT. NDAT enhancedd gefitinib-induced antiproliferation in gefitinib
      resistant colorectal cancer cells by inhibiting ST6Gal1 activity and PI3K
      activation. Furthermore, NDAT enhanced gefitinib-induced anticancer activity
      additively in colorectal cancer HCT116 cell xenograft-bearing nude mice. Results
      suggest that NDAT may have an application with gefitinib as combination
      colorectal cancer therapy.

PMID- 30187357
TI  - Assessing interactive mixture toxicity of carbamate and organophosphorus
      insecticides in the yabby (Cherax destructor).
AB  - Carbamate (CB) and organophosphorus (OP) pesticides are commonly detected in
      aquatic ecosystems and predominantly occur as mixtures of varying complexity.
      These pesticides inhibit the activity of total cholinesterase (ChE) and thus have
      the potential to interfere with behaviours that may be essential for the survival
      of aquatic species. Although the effects of individual ChE insecticides on
      aquatic species have been reported for decades, the neurotoxicity of mixtures is
      still poorly understood. This study examined the chronic toxicities of two OP
      insecticides (chlorpyrifos (CPF) and malathion (MAL)) and one carbamate
      insecticide (methomyl (METH)) in binary and ternary mixtures on the ChE activity
      of the yabby (C. destructor). Using the concentration addition approach to
      estimate mixture toxicity, the observed inhibition of ChE activity caused by all
      binary mixtures of CPF plus MAL, CPF plus METH and MAL plus METH was additive. In
      ternary mixtures, all combinations of CPF, MAL and METH were either additive or
      antagonistic depending on the relative ratios of these chemicals in the mixtures.
      The effect of mixtures of these three insecticides on C. destructor has not
      previously been assessed, and the data suggest that individual chemical risk
      assessments are likely to incorrectly estimate the effect of these insecticides
      on C. destructor in the aquatic environment where combinations of such chemicals
      occur.

PMID- 30187358
TI  - Ingestion of inorganic mercury by juvenile black tiger prawns (Penaeus monodon)
      alters biochemical markers.
AB  - There is a lack of information regarding the effects on biochemical markers in
      invertebrates diet-exposed to inorganic mercury. In the present study, juvenile
      black tiger prawn (Penaeus monodon) were fed with food dosed with mercuric
      chloride (low: 0.2 mg kg-1; medium: 0.77 mg kg-1; high: 1.41 mg kg-1; higher:
      2.52 mg kg-1) and control (0.03 mg kg-1) over 12 days. At the end of exposure
      periods, ventral nerve cord, compound eyes and muscle were dissected for
      biochemical marker analyses (acetylcholinesterase - AChE; lipoperoxidation - LPO;
      glutathione S-transferase - GST; catalase - CAT). Prawn muscle showed an increase
      in total mercury concentration over time for low and high treatments, but did not
      show an accumulation in comparison to controls. AChE activity tended to decrease
      over time in all tissues. CAT activity increased over time in controls and lower
      dose treatments but was suppressed in the higher treatment relative to controls
      on day 12; indicating that inorganic mercury is impacting the normal stress
      response by reducing the capacity to degrade hydrogen peroxide. In contrast, no
      effect was observed in LPO and GST activity. A depuration treatment was performed
      and compared to medium treatment; only AChE and GST activities from muscle showed
      significant difference, with AChE activity from depuration treatment lower than
      medium treatment, while the opposite was observed in GST activity. Overall, the
      low mercury accumulation observed over 12 days of exposure may have limited the
      biochemical stress responses, which could also have limited the detection of
      differences in the depuration treatment relative to medium treatment.

PMID- 30187359
TI  - Imidacloprid alters ant sociobehavioral traits at environmentally relevant
      concentrations.
AB  - Much research has focused on the effects of neonicotinoids on honey bees,
      however, relatively few studies have investigated their effects on ants, a
      taxonomically-related eusocial insect of high ecological importance. This study
      quantified how dietary exposures to environmentally-relevant levels of a
      neonicotinoid insecticide (imidacloprid) affected foraging and nest building of
      the western harvester ant over 14 days. Using a replicated design, statistically
      significant reductions in ant foraging success (50% or greater) occurred at
      concentrations as low as 50 ppb compared to controls. Both the number of ants
      entering the maze and the percentage of foraging ants able to locate food were
      impacted by imidacloprid exposure. Ants exposed to 50 ppb also took three times
      longer than controls to find food in a test maze. This concentration is among the
      lowest levels of imidacloprid reported to affect ants and is well within the
      range of concentrations found in pollen and nectar of imidacloprid-treated
      plants. Ant foraging success was also impaired at comparable levels as those
      reported for the honey bee. Although more refinement and research are needed,
      results from this study suggest that the western harvester ant may be useful for
      screening the effects of neurotoxic chemicals on their navigation and foraging,
      two behaviors which are critical to maintaining colony health of ants and the
      ecological services they provide.

PMID- 30187360
TI  - Neural time course and brain sources of facial attractiveness vs. trustworthiness
      judgment.
AB  - Prior research has shown that the more (or less) attractive a face is judged, the
      more (or less) trustworthy the person is deemed and that some common neural
      networks are recruited during facial attractiveness and trustworthiness
      evaluation. To interpret the relationship between attractiveness and
      trustworthiness (e.g., whether perception of personal trustworthiness may depend
      on perception of facial attractiveness), we investigated their relative neural
      processing time course. An event-related potential (ERP) paradigm was used, with
      localization of brain sources of the scalp neural activity. Face stimuli with a
      neutral, angry, happy, or surprised expression were presented in an
      attractiveness judgment, a trustworthiness judgment, or a control (no explicit
      social judgment) task. Emotional facial expression processing occurred earlier
      (N170 and EPN, 150-290 ms post-stimulus onset) than attractiveness and
      trustworthiness processing (P3b, 400-700 ms). Importantly, right-central ERP (C2,
      C4, C6) differences reflecting discrimination between "yes" (attractive or
      trustworthy) and "no" (unattractive or untrustworthy) decisions occurred at least
      400 ms earlier for attractiveness than for trustworthiness, in the absence of LRP
      motor preparation differences. Neural source analysis indicated that facial
      processing brain networks (e.g., LG, FG, and IPL-extending to pSTS), also right
      lateralized, were involved in the discrimination time course differences. This
      suggests that attractiveness impressions precede and might prime trustworthiness
      inferences and that the neural time course differences reflect truly facial
      encoding processes.

PMID- 30187361
TI  - Unexpected Benefit from Alpelisib and Fulvestrant in a Woman with Highly Pre
      treated ER-Positive, HER2-Negative PIK3CA Mutant Metastatic Breast Cancer.
AB  - We present the case of a postmenopausal patient with a secondary metastatic ER
      positive, HER2-negative breast cancer who was successfully treated with
      fulvestrant and alpelisib following six lines of therapy. The tumour showed two
      uncommon PIK3CA mutations, and with the combination of alpelisib and fulvestrant
      the patient went from ECOG grade 3, before the start of this therapy, to ECOG
      grade 1 during treatment until progressive disease after 6 months. This
      unexpected benefit emphasizes the importance of performing a Next Generation
      Sequencing (NGS)-based assay to screen for several cancer genes in the metastatic
      setting, even after more than four lines of therapy and a high ECOG grade.
      Moreover, the use of alpelisib may be beneficial for uncommon PIK3CA mutations.

PMID- 30187364
TI  - Implementation of a Statewide Program to Promote Safe Sleep, Breastfeeding and
      Tobacco Cessation to High Risk Pregnant Women.
AB  - Infant mortality remains a problem in the United States with sleep-related deaths
      accounting for a significant portion. Known risk reduction strategies include
      breastfeeding, avoiding tobacco use and following the American Academy of
      Pediatrics' safe sleep guidelines. The purpose of this project was to evaluate
      outcomes of Safe Sleep Instructor-led community baby showers, which included safe
      sleep promotion, breastfeeding promotion and tobacco cessation education.
      Certified Safe Sleep Instructors (n = 35) were trained on how to plan and host a
      Community Baby Shower to provide education to pregnant women of low socioeconomic
      status or with high risk of infant mortality. Eighteen Community Baby Showers
      were held across two urban and eight rural counties in Kansas. Surveys were
      administered pre- and post-event to assess participant knowledge, confidence and
      intentions to follow through with planned action related to safe sleep,
      breastfeeding and reducing tobacco risk. Matched data were summarized and
      evaluated for differences using McNemar's and Wilcoxon Signed Rank tests.
      Significant increases were observed in Baby Shower participants' (n = 845)
      reported plans to follow the AAP Safe Sleep guidelines (all p < 0.001),
      likelihood to breastfeed (p < 0.001), confidence in ability to breastfeed for
      more than 6 months (p < 0.001), knowledge of local breastfeeding support
      resources (p < 0.001), knowledge of ways to avoid second-hand smoke exposure (p <
      0.001) and knowledge of local tobacco cessation services (p = 0.004). Based on
      the result of the pre- and post-event surveys, certified Safe Sleep Instructors
      were able to plan and host successful events to increase knowledge and confidence
      related to risk reduction strategies to reduce sleep-related infant deaths.

PMID- 30187363
TI  - Sjogren's Syndrome and Autoimmune Thyroid Disease: Two Sides of the Same Coin.
AB  - The coexistence of Sjogren's syndrome (SS) and autoimmune thyroid disease (AITD)
      has been documented. However, there is no consensus whether this coexistence
      should be considered as the same nosological condition or as polyautoimmunity.
      Thus, in this monocentric retrospective study, patients with SS alone (i.e.,
      primary) were compared with patients with SS and AITD. In addition, a discussion
      of previous studies including those about genetic and environmental factors
      influencing the development of both conditions is presented. In our series, all
      patients with AITD had Hashimoto's thyroiditis (HT). No significant differences
      in age, gender, age of disease onset, and disease duration were found between the
      two groups. Lymphadenopathy and urticaria were more frequently registered in
      patients with SS-HT than in patients with SS alone (p < 0.05). Anti-Ro/SSA
      antibodies were more frequent in the primary SS group (p = 0.01). SS-HT patients
      were more likely to report a positive history of smoking (p = 0.03). The clinical
      expression of SS varies slightly when HT coexists. Although both entities share
      common physiopathological mechanisms as part of the autoimmune tautology, they
      are nosologically different and their coexistence should be interpreted as
      polyautoimmunity. Further studies based on polyautoimmunity would allow
      establishing a new taxonomy of autoimmune diseases.

PMID- 30187365
TI  - Migrants et migrants? Tensions mondiales entre accueil et rejet : Migrants and
      migrants? Global tensions between welcome and rejection.

PMID- 30187362
TI  - An Update in Antimicrobial Therapies and Infection Prevention in Pediatric Lung
      Transplant Recipients.
AB  - Lung transplantation can offer life-prolonging therapy to children with otherwise
      terminal end-stage lung disease. However, infectious complications, like those
      experienced by their adult counterparts, are a significant cause of morbidity and
      mortality. These include bacteria, viruses, and fungi that infect the patient
      pretransplant and those that may be acquired from the donor or by the recipient
      in the months to years posttransplant. An understanding of the approach to the
      management of each potential infecting organism is required to ensure optimal
      outcomes. In particular, emphasis on aggressive preoperative management of
      infections in pediatric patients with cystic fibrosis is important. These include
      multidrug-resistant Gram-negative bacteria, fungi, and Mycobacterium abscessus,
      the posttransplant outcome of which depends on optimal pretransplant management,
      including vaccination and other preventive, antibiotic-sparing strategies.
      Similarly, increasing the transplant donor pool to meet rising transplant demands
      is an issue of critical importance. Expanded-criteria donors-those at increased
      risk of blood-borne viruses in particular-are increasingly being considered and
      transplants undertaken to meet the rising demand. There is growing evidence in
      the adult pool that these transplants are safe and associated with comparable
      outcomes. Pediatric transplanters are therefore likely to be presented with
      increased-risk donors for their patients. Finally, numerous novel antibiotic
      sparing therapeutic approaches are on the horizon to help combat infections that
      currently compromise transplant outcomes.

PMID- 30187366
TI  - HLA-DQB1*06:02 allele frequency and clinic-polysomnographic features in Saudi
      Arabian patients with narcolepsy.
AB  - BACKGROUND: Narcolepsy is an uncommon neurological disorder characterised by
      irresistible spells of sleep associated with abnormal rapid eye movement (REM)
      sleep. The association between narcolepsy and human leukocyte antigen HLA-
      DQB1*06:02 has been established elsewhere but remains to be investigated among
      Saudi Arabian patients with narcolepsy. METHODS: A total of 29 Saudi patients
      with type I or type 2 narcolepsy comprising of 23 (79%) males and 6 (21%) females
      with a mean age of 17.2 +/- 9.6 years were included in this study. Type 1 or type
      2 narcolepsy was diagnosed by full polysomnography followed by a multiple sleep
      latency test in accordance with International Classifications of Sleep Disorders
      3 criteria. HLA typing for DQB1 alleles was performed by polymerase chain
      reaction and hybridization with sequence-specific oligonucleotide probes.
      Differences in clinical and sleep parameters were compared by univariable
      analyses. HLA-DQB1*06:02 frequency was systematically compared with the published
      literature. RESULTS: Type 1 narcolepsy was diagnosed in 19/29 (65.5%) patients,
      whereas 10/29 (34.5%) patients had type 2 narcolepsy. DQB1*06:02 was present in
      25/29 (86.2%) patients; 15/19 (78.9%) narcolepsy type 1 patients and 10/10 (100%)
      narcolepsy type 2 patients harboured the DQB1*06:02 allele. REM latency was
      significantly lower in DQB1*06:02-positive patients compared to DQB1*06:02
      negative patients (17.6 +/- 32.3 min vs. 106.0 +/- 86.0 min; p = 0.025). Epworth
      Sleepiness Scale scores were significantly higher among type 1 than type 2
      narcolepsy patients (19.7 +/- 3.2 vs 15.3 +/- 3.6; p = 0.02). CONCLUSIONS:
      DQB1*06:02 allele frequencies among Saudi patients with narcolepsy were
      consistent with previously published data.

PMID- 30187367
TI  - Parent-child co-sleeping in children with co-morbid conditions and sleep
      disordered breathing.
AB  - PURPOSE: Co-sleeping is common in children with co-morbid conditions. The aim of
      the study was to analyze the prevalence and determinants of parent-child co
      sleeping in children with co-morbid conditions and sleep-disordered breathing and
      the impact on parental sleep. METHODS: Parents of consecutive children undergoing
      a sleep study filled in a questionnaire on co-sleeping. RESULTS: The parents of
      166 children (80 boys, median age 5.7 years (0.5-21) participated in this study.
      The most common co-morbid conditions of the children were Down syndrome (17%),
      achondroplasia (11%), and Chiari malformation (8%). The prevalence of parent
      child co-sleeping was 46%. Reasons for co-sleeping were mainly reactive and
      included child's demand (39%), crying (19%), nightmares (13%), medical reason
      (34%), parental reassuring or comforting (27%), and/or over-crowding (21%). Sixty
      eight percent of parents reported that co-sleeping improved their sleep quality
      because of reassurance/comforting (67%), reduced nocturnal awakening (23%), and
      child supervision (44%). Forty percent of parents reported that co-sleeping
      decreased their sleep quality because of nocturnal awakenings or early wake up,
      or difficulties initiating sleep (by 77% and 52% of parents, respectively),
      whereas both positive and negative associations were reported by 29% of the
      parents. Co-sleeping was more common with children < 2 years of age as compared
      to older children (p < 0.001). CONCLUSIONS: Parent-child co-sleeping is common in
      children with co-morbid conditions and sleep-disordered breathing. Co-sleeping
      was mainly reactive and had both positive and negative associations with parental
      sleep quality. Co-sleeping should be discussed on an individual basis with the
      parents in order to improve the sleep quality of the family.

PMID- 30187369
TI  - Hyperornithinemia, Hyperammonemia, and Homocitrullinuria Syndrome Causing Severe
      Neonatal Hyperammonemia.
AB  - Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome (OMIM 238970)
      is an autosomal recessive disorder that is caused by a deficiency of
      mitochondrial ornithine transporter 1, resulting in dysfunction of the urea
      cycle. HHH is the rarest of the urea cycle disorders, reported in fewer than 100
      patients. It is characterized by extreme phenotypic variability, including
      diverse ages of onset and severity of phenotype. We report the first confirmed
      instance of HHH syndrome in a premature infant (31 2/7 weeks) with severe
      hyperammonemia (1,300 MUmol/L).This case highlights the importance of considering
      HHH in the differential diagnosis for neonatal hyperammonemia. Because HHH is not
      detected by newborn screening, and the characteristic biochemical triad may be
      subtle or even absent, it has the potential to be underdiagnosed; however, making
      the diagnosis has critical therapeutic implications as treatment is distinct from
      other urea cycle defects. For instance, lysine supplementation is a beneficial
      treatment unique to HHH. Therefore, we present here a review of previously
      reported cases in order to demonstrate the full spectrum of the disease and
      highlight potentially diagnostic features.

PMID- 30187368
TI  - Evaluation of body position in upper airway stimulation for obstructive sleep
      apnea-is continuous voltage sufficient enough?
AB  - PURPOSE: The definition of positional obstructive sleep apnea (POSA) is widely
      accepted as a difference of 50% or more in AHI between supine and non-supine
      position. Upper airway stimulation (UAS) is an effective treatment for OSA but
      the implant delivers a single voltage over sleep period without consideration of
      body position. Clinical practice suggests different outcomes for OSA in supine
      position under UAS treatment. METHODS: Outcomes of 44 patients were analyzed 12
      months after implantation in a two-center, prospective consecutive trial in a
      university hospital setting. Total night and supine AHI were evaluated and the
      ratio of time spent in supine was considered. Correlation between the classic and
      the modified definition of POSA and treatment response were evaluated. RESULTS:
      The time ratio spent in supine position did not differ before implantation and
      after 12 months. Total and supine AHI were reduced with the use of UAS therapy (p
      < 0.001) but both the baseline and final supine AHI were higher than total night
      AHI. Considering POSA definition as a ratio of supine to non-supine AHI, there
      was no clear cutoff for defining responders neither with nor without the
      additional component of time in supine position. CONCLUSIONS: The OSA reduction
      is strong for the total AHI and supine AHI. Nonetheless, here, there is no cutoff
      for defining POSA as critical for UAS therapy response. Therefore, there is no
      evidence for excluding POSA patients from UAS in general. Future technology
      improvement should take body position and adaptive voltage into account.

PMID- 30187370
TI  - Reversible Cerebral White Matter Abnormalities in Homocystinuria.
AB  - Striking MRI brain changes resembling leukoencephalopathy are rarely seen in
      classical homocystinuria. Our case suggests that reversible white matter changes
      (WMC) are linked to elevated plasma methionine levels arising during treatment.A
      6-year-old boy with learning difficulties and a normal MRI brain scan was
      diagnosed with homocystinuria (initial total homocysteine 344 MUmol/L and
      methionine 64 MUmol/L). At the age of 6.5 years, he developed superior sagittal
      sinus (SSS) thrombosis. Antithrombotic and homocysteine-lowering treatments were
      started. Due to poor dietary compliance and betaine treatment, his methionine
      level reached 1,285 MUmol/L, and left side weakness developed. Repeat MRI scan
      revealed new confluent WMC in previously myelinated brain areas. Further 3-month
      treatment with tighter dietary control significantly dropped his methionine level
      (233 MUmol/L) with resolution of his neurological deficit and of radiological
      changes.We suggest a reversible toxicity from hypermethioninaemia as a possible
      source of cerebral WMC (secondary to a demyelinating process) in patients with
      homocystinuria. It highlights the importance of homocysteine-lowering treatment
      as a prevention and complete resolution of neurological complications. It also
      demonstrates the need to consider homocystinuria in a differential diagnosis of
      paediatric leukoencephalopathy.

PMID- 30187372
TI  - Reviewers in 2018.

PMID- 30187371
TI  - Screening for Niemann-Pick Type C Disease in a Memory Clinic Cohort.
AB  - Niemann-Pick type C disease (NPC) is a neurovisceral lysosomal storage disorder
      with a heterogeneous phenotype including ataxia, cognitive impairment, impairment
      of vertical saccades, and psychiatric symptoms, among many others. Based on
      clinical, genetic, and biomarker findings, recent guidelines put forward a
      screening for atypical and oligosymptomatic forms of NPC in clinical niches with
      an increased risk. Here, we report methods and results of a negative screening
      study in the niche of a memory clinic. We retrospectively and prospectively
      identified 83 patients with unclassified cognitive impairment (15 dementia, 46
      mild cognitive impairment, and 22 progressive subjective cognitive decline)
      before 60 years of age (82 patients between 41 and 60 years). We explored the
      prevalence of clinical features compatible with NPC and measured plasma levels of
      chitotriosidase and cholestantriol. The NPC suspicion index indicated high
      probability for NPC in 3 and moderate probability in 16 patients. Prevalent (>5%)
      neurological and psychiatric features were depression, seizures, ataxia,
      dysarthria, and psychotic symptoms. Vertical gaze palsy without parkinsonism was
      observed in one patient. Cholestantriol levels were only abnormal in one patient.
      Chitotriosidase levels were susceptible to slight elevations that were
      reproducible in only two of five patients. Our study does not exclude NPC among
      memory clinic patients. Instead, we suggest conducting prospective screening
      studies in younger cohorts that include a focused neurological examination.
      Excluding minor cognitive impairment and discarding depression as an independent
      disease symptom probably further improve screening effectivity but may delay or
      miss therapeutic options in early or mild disease.

PMID- 30187373
TI  - Capsule Commentary on Crapanzano et al., An Exploration of Residents' Implicit
      Biases Towards Depression-a Pilot Study.

PMID- 30187374
TI  - Emergency Department Care for Patients with Limited English Proficiency: a
      Retrospective Cohort Study.
AB  - BACKGROUND: Limited English proficiency (LEP) patients may be particularly
      vulnerable in the high acuity and fast-paced setting of the emergency department
      (ED). OBJECTIVE: To compare the care processes of LEP patients in the ED. DESIGN:
      Retrospective cohort study. SETTING: ED in a large tertiary care academic medical
      center. PATIENTS: Adult LEP and English Proficient (EP) patients during their
      index presentation to the ED from September 1, 2013, to August 31, 2015. LEP
      patients were identified as those who selected a preferred language other than
      English when registering for care. MAIN MEASURES: Rates of diagnostic studies,
      admission, and return visits for those originally discharged from the ED. KEY
      RESULTS: We studied 57,435 visits of which 5241 (9.1%) were for patients with
      LEP. In adjusted analyses, LEP patients were more likely to receive an X
      ray/ultrasound (OR 1.11, CI 1.03-1.19) and be admitted to the hospital (OR 1.09,
      CI 1.01-1.19). There was no difference in 72-h return visits (OR 0.98, CI 0.73
      1.33). LEP patients presenting with complaints related to the cardiovascular
      system were more likely to receive a stress test (OR 1.51, CI 1.22-1.86), and
      those with gastrointestinal diagnoses were more likely to have an X
      ray/ultrasound (OR 1.31, CI 1.02-1.68). In stratified analyses, Spanish speakers
      were less likely to be admitted (OR 0.8, CI 0.70-0.91), but those preferring
      "other" languages, which were all languages with < 500 patients, had a
      statistically significant higher adjusted rate of admission (OR 1.35, CI 1.17
      1.57). CONCLUSIONS: ED patients with LEP experienced both increased rates of
      diagnostic testing and of hospital admission. Research is needed to examine why
      these differences occurred and if they represent inefficiencies in care.

PMID- 30187375
TI  - Capsule Commentary on Franklin et al., Time to Filling of New Prescriptions for
      Chronic Disease Medications Among a Cohort of Elderly Patients in the USA.

PMID- 30187376
TI  - A Comparison of Electronic Patient-Portal Use Among Patients with Resident and
      Attending Primary Care Providers.
AB  - BACKGROUND: Electronic patient-portals offer the potential to enhance patient
      physician communication and health outcomes but differential use may create or
      worsen disparities. While prior studies identified patient characteristics
      associated with patient-portal use, the role of physician factors is less known.
      We investigated differences in overall and patterns of portal use for patients
      with resident and attending primary care providers (PCPs). METHODS: Cross
      sectional study of all established patients with a resident or attending PCP seen
      at an academic internal medicine practice (two sites) between May 1, 2014, and
      April 30, 2015. We defined patient-portal use as having accessed any "active"
      (secure messaging, medication refill request), or "passive" (viewing labs, after
      visit summaries, or appointments) patient-portal function more than once over the
      study period. We used generalized linear models clustered on PCP to examine the
      odds of patient-portal use by PCP type, adjusted for patient age, gender,
      preferred language, race/ethnicity, insurance, and visits. Among patient-portal
      users, we examined the association of PCP type with "active use" utilizing the
      same method. RESULTS: The mean patient age (n = 17,699) was 54.2 (SD 17.5), with
      47.2% White, 23.6% Asian, 8.8% Black, 8.4% Latino, and 12% other/unknown. The
      majority (61.8%) had private insurance, and attending PCPs (76.9%). Although
      72.3% enrolled in the patient-portal, only 53.4% were portal users; 40.0% were
      active users. There were 47 attending and 62 resident physicians. Patients with
      resident PCPs had lower odds of using the portal compared to those with attending
      PCPs (OR = 0.54, 95% CI 0.50-0.59). Similarly, among portal users, residents'
      patients had lower odds of being active users of the portal (OR = 0.76, 95% CI
      0.68-0.87). CONCLUSION: Given the lower patient-portal use among residents'
      patients, residency programs should develop curricula to bolster trainee
      competence in using the patient-portal for communication and to enhance the
      patient-physician relationship. Future research should explore additional
      physician factors that impact portal use.

PMID- 30187377
TI  - The Association between Mental Health Disorders and History of Unintended
      Pregnancy among Women Veterans.
AB  - BACKGROUND: Women Veterans have high rates of mental health disorders and other
      psychosocial factors which may render this population particularly vulnerable to
      negative health outcomes associated with unintended pregnancy. OBJECTIVE: The
      objective of our study was to assess the relationship between self-reported
      mental illness and history of unintended pregnancy among women Veterans. DESIGN
      AND PARTICIPANTS: Data are from a nationally representative, cross-sectional
      telephone survey of women Veterans, ages 18-45, who used VA for primary care
      within 12 months prior to interview (survey completion rate 83%). MAIN MEASURES:
      Predictors were self-report of any and number of mental health disorders
      (depression, anxiety, post-traumatic stress disorder, bipolar disorder, or
      schizophrenia). Outcomes were any and number of unintended pregnancies.
      Multivariable logistic and negative binomial regression were used to assess
      relationships between mental illness and unintended pregnancy. To assess women's
      current risk of unintended pregnancy, we examined associations between any mental
      health disorder and contraceptive use at last sex among heterosexually active
      women not desiring pregnancy. KEY RESULTS: Among 2297 women Veterans, 1580
      (68.8%) reported a history of at least one mental health disorder, with 20.1,
      21.6, and 27.0% reporting one, two, or three or more conditions, respectively.
      Any history of unintended pregnancy was reported by 1315 women (57.3%); 28.3%
      reported one, 15.6% reported two, and 13.4% reported three or more. Compared to
      women with no mental illness, women with any mental health disorder were more
      likely to report any unintended pregnancy (60.3 vs. 50.5%; adjusted OR 1.40; 95%
      CI 1.15, 1.71) and to have experienced greater numbers of unintended pregnancies
      (adjusted incidence rate ratio 1.29; 95% CI 1.15, 1.44). Increasing numbers of
      mental health disorders were associated with greater numbers of unintended
      pregnancies. Contraceptive use and method efficacy at last sex did not differ by
      mental health status. CONCLUSIONS: Women Veterans with mental health disorders
      are more likely to have experienced any and greater numbers of unintended
      pregnancies than Veterans without mental health disorders.

PMID- 30187378
TI  - Independent Relationship of Changes in Death Rates with Changes in US
      Presidential Voting.
AB  - BACKGROUND: The outcome of the 2016 presidential election is commonly attributed
      to socioeconomic and ethnic/racial issues, but health issues, including "deaths
      of despair," may also have contributed. OBJECTIVE: To assess whether changes in
      age-adjusted death rates were independently associated with changes in
      presidential election voting in 2016 vs. 2008. DESIGN: We used publicly available
      data in each of 3112 US counties to correlate changes in a county's presidential
      voting in 2016 compared with 2008 with recent changes in its age-adjusted death
      rate, after controlling for population and rural-urban status, median age,
      race/ethnicity, income, education, unemployment rate, and health insurance rate.
      DESIGN SETTING: Cross-sectional analysis of county-specific data.
      SETTING/PARTICIPANTS: All 3112 US counties. MAIN MEASURES: The independent
      correlation of a county's change in age-adjusted death rate between 2000 and 2015
      with its net percentage Republican gain or loss in the presidential election of
      2016 vs. 2008. KEY RESULTS: In 2016, President Trump increased the Republican
      presidential vote percentage in 83.8% of counties compared with Senator McCain in
      2008. Counties with an increased Republican vote percentage in 2016 vs. 2008 had
      a 15% higher 2015 age-adjusted death rate than counties with an increased
      Democratic vote percentage. Since 2000, overall death rates declined by less than
      half as much, and death rates from drugs, alcohol, and suicide increased 2.5
      times as much in counties with Republican gains compared with counties with
      Democratic gains. In multivariable analyses, Republican net presidential gain in
      2016 vs. 2008 was independently correlated with slower reductions in a county's
      age-adjusted death rate. Although correlation cannot infer causality, modest
      reductions in death rates might theoretically have shifted Pennsylvania,
      Michigan, and Wisconsin to Secretary Clinton. CONCLUSIONS: Less of a reduction in
      age-adjusted death rates was an independent correlate of an increased Republican
      percentage vote in 2016 vs. 2008. Death rates may be markers of dissatisfactions
      and fears that influenced the 2016 Presidential election outcomes.

PMID- 30187379
TI  - Unmasking and successful management of light chain deposition disease of kidney
      in pregnancy: a complex case, mirroring the complex needs of pregnancy with
      kidney disease in India.
AB  - Pregnancy offers a precious window of opportunity to diagnose previously
      undetected or new onset kidney diseases in emerging countries like India, where
      access to medical, educational and health care facilities are not equitably
      distributed across varied sections of society. We report a case of a 33 year-old
      primi gravida who had a successful pregnancy following what was initially
      considered to represent preeclampsia at 38 weeks of gestation, in whom a
      subsequent kidney biopsy for persistence of pregnancy-related acute kidney injury
      (Pr-AKI) revealed light chain deposition disease (LCDD). The etiological
      evaluation of LCDD led to the detection of an underlying plasma cell dyscrasia
      which was treated effectively with chemotherapy and autologous stem cell
      transplant. In this report, we explore the hitherto uncharted pathophysiological
      relationship between LCDD and pregnancy-related kidney injury by transmission
      electron microscopic (TEM) studies of endothelial injury in this setting, and
      underscore the benefits of medical care in a multidisciplinary environment which
      yielded gratifying results in preservation of maternal kidney health and fetal
      outcome.

PMID- 30187380
TI  - Comparing the impact of older age on outcome in chronic kidney disease of
      different etiologies: a prospective cohort study.
AB  - BACKGROUND: In older patients with chronic kidney disease (CKD), the risk of
      progression to end stage renal disease and cardiovascular death both differ
      compared to younger patients. This likely reflects differences in case mix and co
      morbid burdens. We sought to establish the extent to which age itself is an
      independent biomarker of adverse outcome in CKD. METHODS: This was an analysis of
      the Salford Kidney Study, a prospective, longitudinal, observational study of
      2,667 patients with eGFR < 60 ml/min/1.73 m2. Patients were divided into four age
      groups (< 55, 55-65, 65-75 and > 75 years). Within group adjusted hazard ratios
      for death in older compared to younger patients were calculated for different
      primary renal diseases. A competing risk model of death and renal replacement
      therapy (RRT) as outcomes was performed. RESULTS: The median age of the cohort
      was 67.1 years [interquartile range (IQR): 55.6-75.3] and median eGFR 30.8
      ml/min/1.73 m2 (IQR: 20.6-43.2). Follow up was 3.5 +/- 2.9 years. Overall, the
      adjusted HR for death in patients aged > 75 years compared to those < 55 years
      was 4.4 (95% CI 3.4-5.9), p < 0.001. The HR for death differed between primary
      renal diseases and CKD stages. In diabetic nephropathy, the HR was 3.0 (1.8-5.3,
      p < 0.001), in glomerulonephritis the HR was 12.2 (5.6-25.5, p < 0.001). The
      cumulative incidence of RRT was < 0.1 at 10 years for patients > 75 years,
      compared with 0.50 in those < 55 years. Death was more likely at 20 months in
      those aged 75 years or older (0.17) than at 10 years in those aged < 55 years
      (0.10). CONCLUSION: This study demonstrates that the risk associated with older
      age shows significant variability between primary renal diseases. This is whilst
      acknowledging that observational studies carry the risk of hidden bias not
      adjusted for in the statistical model.

PMID- 30187381
TI  - Acute kidney injury following coronary angiography: a nationwide study of
      incidence, risk factors and long-term outcomes.
AB  - BACKGROUND: We studied the incidence and risk factors of acute kidney injury
      (AKI) following coronary angiography (CA) and examined short- and long-term
      outcomes of patients who developed AKI, including progression of chronic kidney
      disease (CKD). METHODS: This was a retrospective study of all patients undergoing
      CA in Iceland from 2008 to 2015, with or without percutaneous coronary
      intervention. All procedures were performed with iso-osmolar contrast. AKI was
      defined according to the SCr component of the KDIGO criteria. Patients without
      post-procedural SCr were assumed to be free of AKI. Incident CKD was defined as
      90-day sustained estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2,
      and progression of CKD as worsening at least one stage sustained over 90 days.
      RESULTS: AKI was detected in 231 of 13,561 cases (1.7%). There was an interaction
      between contrast dose and preexisting kidney function, where the risk for AKI was
      only significant at a dose > 150 mL in patients with baseline eGFR < 45
      mL/min/1.73 m2 (OR 5.3, 95% CI 2.1-14.2). The AKI patients had worse short-and
      long-term survival, as well as elevated hazard of both new-onset CKD (HR 3.7, 95%
      CI 2.7-5.0) and progression of preexisting CKD (HR 2.0, 95% CI 1.5-2.6) over a
      median follow-up of 3.3 years (range 0.1-8.4 years), compared to a propensity
      score-matched control group. CONCLUSIONS: For iso-osmolar contrast, the risk of
      AKI related to contrast dose was evident for higher amount of contrast in
      patients with baseline eGFR < 45 mL/min/1.73 m2. In addition to association with
      adverse short- and long-term survival AKI had a strong association with new-onset
      or progression of CKD when patients were followed longitudinally.

PMID- 30187383
TI  - Work participation in ADHD and associations with social characteristics,
      education, lifetime depression, and ADHD symptom severity.
AB  - The literature refers to high rates of occupational failure in the population of
      adults with ADHD. The explanation for this is less known. The aim of the present
      study was to examine associations between social characteristics and clinical
      features of adults with ADHD and their occupational outcome. Out of 1050 patients
      diagnosed with ADHD in a specialized outpatient clinic between 2005 and 2017, 813
      (77.4%) agreed to participate in the study. ADHD was diagnosed according to DSM
      IV criteria, and ADHD subtypes recorded accordingly. Lifetime depression was
      diagnosed using the specific module of the Mini International Neuropsychiatric
      Interview. Occupational status and other social characteristics like marital
      status and living with children were recorded. Intelligence (IQ) and symptom
      severity of ADHD (ASRS score) were assessed in subsamples of participants (n =
      526 and n = 567, respectively). In this sample of adults with ADHD (mean age 36.9
      years, 48.5% women), 55.3% of the women and 63.7% of the men were working at the
      time of inclusion. Work participation was associated with being male, being
      married or cohabitant, or living with children, as well as a life story without
      major depression. Age, education, ADHD subtype, and ADHD symptom severity were
      not significantly associated with work participation. Neither was IQ when
      adjusted for other covariates. Occupational outcome in adults with ADHD appears
      to be more associated with social characteristics and a history of depression,
      rather than with IQ, ADHD subtype, or ADHD symptom severity.

PMID- 30187382
TI  - Definition of a new cut-off for the anti-phospholipase A2 receptor (PLA2R)
      autoantibody immunoassay in patients affected by idiopathic membranous
      nephropathy.
AB  - Autoantibodies against phospholipase A2 receptor (PLA2R) are a sensitive and
      specific marker for idiopathic membranous nephropathy (IMN). The aim of our study
      was to redefine the cut-off value for the measurement of anti-PLA2R autoantibody
      levels by an automated enzyme immunoassay, in a large single-center cohort of
      Italian IMN patients at the time of diagnosis. Sixty-seven consecutive incident
      patients, with biopsy-proven IMN, were recruited. All patients were naive to
      preceding immunosuppressive therapeutic regimens. The patient population had a
      mean age of 57 years and included 48 males and 19 females. Also, 200 patients
      with other renal diseases and 36 healthy subjects were studied as controls. The
      anti-PLA2R autoantibody levels were measured using the commercial enzyme-linked
      immunosorbent assay kit at the time of renal biopsy. At a cut-off value of 2.7
      RU/ml (significantly lower than the manufacturer's recommended value of 14
      RU/ml), calculated by receiver operating characteristic curves, the sensitivity
      and specificity of anti-PLA2R autoantibodies in the diagnosis of IMN was 88.1 and
      96% respectively. The adapted cut-off value of 2.7 UI/ml increased sensitivity
      without affecting the specificity and it should be the recommended value for this
      method. Additionally our study confirmed the correlation, at baseline, between
      anti-PLA2R autoantibody levels and other biomarkers of disease activity.

PMID- 30187384
TI  - Citalopram Reduces Aggregation of ATXN3 in a YAC Transgenic Mouse Model of
      Machado-Joseph Disease.
AB  - Machado-Joseph disease, also known as spinocerebellar ataxia type 3, is a fatal
      polyglutamine disease with no disease-modifying treatment. The selective
      serotonin reuptake inhibitor citalopram was shown in nematode and mouse models to
      be a compelling repurposing candidate for Machado-Joseph disease therapeutics. We
      sought to confirm the efficacy of citalopram to decrease ATXN3 aggregation in an
      unrelated mouse model of Machado-Joseph disease. Four-week-old YACMJD84.2 mice
      and non-transgenic littermates were given citalopram 8 mg/kg in drinking water or
      water for 10 weeks. At the end of treatment, brains were collected for
      biochemical and pathological analyses. Brains of citalopram-treated YACMJD84.2
      mice showed an approximate 50% decrease in the percentage of cells containing
      ATXN3-positive inclusions in the substantia nigra and three examined brainstem
      nuclei compared to controls. No differences in ATXN3 inclusion load were observed
      in deep cerebellar nuclei of mice. Citalopram effect on ATXN3 aggregate burden
      was corroborated by immunoblotting analysis. While lysates from the brainstem and
      cervical spinal cord of citalopram-treated mice showed a decrease in all soluble
      forms of ATXN3 and a trend toward reduction of insoluble ATXN3, no differences in
      ATXN3 levels were found between cerebella of citalopram-treated and vehicle
      treated mice. Citalopram treatment altered levels of select components of the
      cellular protein homeostatic machinery that may be expected to enhance the
      capacity to refold and/or degrade mutant ATXN3. The results here obtained in a
      second independent mouse model of Machado-Joseph disease further support
      citalopram as a potential drug to be repurposed for this fatal disorder.

PMID- 30187385
TI  - Allopregnanolone Treatment Improves Plasma Metabolomic Profile Associated with
      GABA Metabolism in Fragile X-Associated Tremor/Ataxia Syndrome: a Pilot Study.
AB  - Currently, there is no effective treatment for the fragile X-associated
      tremor/ataxia syndrome (FXTAS), a late-onset neurodegenerative disorder. In this
      pilot study, we evaluated whether allopregnanolone, a natural neurosteroid that
      exerts beneficial effects in neurodegenerative diseases, nervous system injury,
      and peripheral neuropathies, could improve lymphocytic bioenergetics and plasma
      pharmacometabolomics in six males with FXTAS (68 +/- 3 years old; FMR1 CGG
      repeats 94 +/- 4; FXTAS stages ranging from 3 to 5) enrolled in a 12-week open
      label intervention study conducted at the University of California Davis from
      December 2015 through July 2016. Plasma pharmacometabolomics and lymphocytic
      mitochondria function were assessed at baseline (on the day of the first
      infusion) and at follow-up (within 48 h from the last infusion). In parallel,
      quantitative measurements of tremor and ataxia and neuropsychological evaluations
      of mental state, executive function, learning, memory, and psychological symptoms
      were assessed at the same time points. Allopregnanolone treatment impacted
      significantly GABA metabolism, oxidative stress, and some of the mitochondria
      related outcomes. Notably, the magnitude of the individual metabolic response, as
      well as the correlation with some of the behavioral tests, was overwhelmingly
      carrier-specific. Based on this pilot study, allopregnanolone treatment has the
      potential for improving cognitive and GABA metabolism in FXTAS aligned with the
      concept of precision medicine.

PMID- 30187386
TI  - Paediatric neck ultrasonography: a pictorial essay.
AB  - The neck structures are located very superficially and are therefore easy to
      explore by ultrasound examination. Ultrasonography is crucial for the detection
      of neck pathologies in children. High-frequency probes (10-15 MHz) are used for
      the ultrasound examination on the patient lying in supine decubitus and with
      their neck stretched out. The outcome of the exam depends mainly on the child's
      cooperation-hence the need for warm sonographic gel and a comfortable cushion to
      place under the patient's shoulders. The complete scan of the neck includes the
      evaluation of the thyroid and salivary glands and the vascular structures as well
      as the lymph node analysis. In children and adolescents, the thymus is often
      visualised in the supraclavicular and jugular scans. It appears as a structure,
      usually hypoechoic, with thin hyperechoic straps, though echogenicity increases
      with age. In this pictorial essay, the main pathological conditions of the neck
      in paediatric age will be examined, such as thyroid dysgenesis, thyroiditis,
      thyroid nodules, lymphadenopathies, cystic lesions, haemangiomas and vascular
      malformation, cervical thymus, fibromatosis colli and pilomatrixoma.

PMID- 30187387
TI  - Exploring the perceived self-efficacy of genetic counselors as teachers.

PMID- 30187388
TI  - End-of-life care in the Dutch medical curricula.
AB  - INTRODUCTION: Future doctors must be trained in giving appropriate care to
      terminal patients. In several countries, medical curricula have been reviewed for
      the attention devoted to end-of-life care (ELC). In the Netherlands, no formal
      review had been performed. Therefore, the aim of this study was to provide an
      overview of the Dutch medical curricula regarding ELC. METHODS: We formed a
      checklist based on international standards consisting of five domains of ELC
      education that are considered essential. Firstly, we studied the Dutch national
      blueprint on medical education. Secondly, using a questionnaire based on the
      checklist we studied the curricula of the eight medical faculties. A
      questionnaire was sent to all Dutch medical faculties to study the compulsory
      courses of the curricula. To assess the elective courses, we consulted the study
      guides. RESULTS: The national blueprint included four of the five domains of ELC.
      None of the eight medical faculties taught all domains specifically on ELC; they
      were taught within other courses. Most attention was given to the domains on
      psychological, sociological, cultural and spiritual aspects; communication and
      conversational techniques; and juridical and ethical aspects. One faculty taught
      an elective course that included all essential aspects of the international
      standards. DISCUSSION: Our study shows that ELC is currently insufficiently
      mentioned in the national blueprint and that none of the faculties fully
      integrated ELC as a part of their compulsory medical curricula. To improve ELC
      education, we recommend the Dutch Federation of University Medical Centres to add
      the five ELC domains to the national blueprint and we recommend the medical
      faculties to review their curricula and offer a separate and compulsory course on
      ELC to prepare their students for their future medical practice.

PMID- 30187389
TI  - Challenges for conducting and teaching handovers as collaborative conversations:
      an interview study at teaching ICUs.
AB  - INTRODUCTION: Whereas medical shift handovers are increasingly recognized to
      fulfil important functions beyond information transfer, studies suggest that
      shift handovers continue to be variably used for reflection, learning or
      discussion. Little is known of the dynamics of incorporating such functions into
      ICU shift handovers, resulting in a challenge for the design of educational
      programs whose underlying philosophies align with the specific requirements of
      the ICU. METHODS: Intensivists, residents and fellows (n = 21) from three ICUs
      were interviewed to determine perceptions of handover functionality and the
      boundaries to what must or can be achieved in handover conversations. Interviews
      were analyzed to isolate training requirements and factors that challenge
      interactions. RESULTS: The analysis revealed that ICU physicians value three
      functions for shift handovers: information transfer, enhancing shared
      understanding and decision-making, and learning. The functions towards which
      physicians are oriented were found to be affected by situational characteristics
      of cases, individuals, teams, and the unit workflow. Whereas some factors are
      helpful cues for determining communication needs, others raise dilemmas and
      misaligned expectations with regards to what can be achieved in the handover.
      DISCUSSION: Our findings add to the growing case for the education of handovers
      in complex settings to involve more than information transfers. As residents gain
      experience, training should be gradually shifted towards more fluid and adaptable
      approaches to the handover and residents' ability to engage in joint reflections
      and discussions. Challenges for engaging in such interactions need to be
      alleviated, in order to allow the redefinition of handovers as potential sources
      of safety and learning, rather than error.

PMID- 30187390
TI  - Workplace mentoring of residents in generic competencies by an independent coach.
AB  - INTRODUCTION: During postgraduate education in pulmonology, supervisors are
      responsible for training residents in generic competencies such as communication,
      professionalism and collaboration, but their focus commonly lies more on medical
      technical competencies. As an alternative approach to supporting residents to
      develop generic skills, we developed a personal mentoring program with a non
      medical professional as mentor. In this study, the residents' experiences with
      the mentoring program were evaluated. METHODS: After an introductory session in
      which individual learning goals were established, pulmonology residents received
      at least six, 60-90-minute, individual, mentoring sessions largely consisting of
      feedback after being observed during daily clinical activities, over a period of
      9 months. The residents' experiences with mentoring were explored through in
      depth interviews followed by a qualitative content analysis. RESULTS: From March
      to November 2016, ten residents in pulmonology completed the program. Despite
      initial scepticism, mentoring encouraged residents to reflect deeply on their
      professional interactions. This caused an increased awareness of the effects of
      their communication and behaviour on patients. Experimenting with communication
      and different behaviours in subsequent interactions felt rewarding and
      contributed to further development, resulting in increased self-confidence and
      job satisfaction. DISCUSSION: Mentoring residents by non-medical coaching was
      associated with improved residents' proficiency in generic competencies.

PMID- 30187392
TI  - Axillary ultrasound-guided core biopsy in breast cancer: identifying higher nodal
      burden and more aggressive clinicopathological characteristics.
AB  - BACKGROUND: Patients with sentinel lymph node (SLN) metastases may not require
      axillary lymph node dissection (ALND) but it remains unclear if patients with a
      positive ultrasound-guided axillary core biopsy (ACB) would satisfy such
      criteria. AIMS: The aim of this study was to assess if breast cancer patients
      with a positive pre-operative ACB have more aggressive tumour
      characteristics/higher axillary nodal burden compared to those with a positive
      SLN. METHODS: Data was extracted from a prospectively maintained breast cancer
      database between 2012 and 2015. Patients who underwent ALND after either positive
      ACB or SLN were included and tumour characteristics/nodal burden were compared.
      RESULTS: One hundred eighty patients underwent ALND, 125/180 after positive ACB
      and 55/180 after positive SLNB. Patients with positive ACB were more likely to
      undergo mastectomy (chi-square test; p = 0.03) and have higher tumour grades
      (Mann-Whitney test; p < 0.01) compared to the SLNB group. Median positive nodes
      excised during ALND were 2 (1-22) and 1 (1-11) for ACB and SLNB groups
      respectively (p < 0.001). Fifty-six patients received neoadjuvant chemotherapy
      (NCT). Of 72/125 patients in the ACB group not receiving NCT, the median number
      of positive nodes was 4 (range, 1-22). Ten patients within the ACB group
      satisfied ACOSOG Z011 criteria. CONCLUSION: Breast cancer patients with a
      positive ACB are more likely to have aggressive tumour characteristics and higher
      nodal burden compared to those identified as having axillary nodal disease on
      SLNB, which may affect surgical decision making.

PMID- 30187391
TI  - Fostering medical students' lifelong learning skills with a dashboard, coaching
      and learning planning.
AB  - INTRODUCTION: To develop lifelong learning skills, students need feedback, access
      to performance data, and coaching. A new medical curriculum incorporated
      infrastructural supports based on self-regulated learning theory and the Master
      Adaptive Learner framework to engage students in reflection and learning
      planning. This study examines students' experience with a performance dashboard,
      longitudinal coaching, and structured time for goal-setting. METHODS: Focus
      groups with first-year medical students explored performance dashboard usage,
      coaching and learning planning. We analyzed findings using thematic analysis.
      Results informed development of a 29-item survey rated strongly disagree (1) to
      strongly agree (5) to investigate experience with the dashboard, coaching and
      learning goals program. The survey was distributed to one first-year medical
      student class. We performed descriptive statistics and factor analysis. RESULTS:
      In three focus groups with 21 participants, students endorsed using the dashboard
      to access performance information but had trouble interpreting and integrating
      information. They valued coaches as sources of advice but varied in their
      perceptions of the value of discussing learning planning. Of 152 students, 114
      (75%) completed the survey. Exploratory factor analysis yielded 5 factors
      explaining 57% of the variance: learning goals development (alpha = 0.88; mean
      3.25 (standard deviation 0.91)), dashboard usage (alpha = 0.82; 3.36 (0.64)),
      coaching (alpha = 0.71; 3.72 (0.64)), employment of learning strategies (alpha =
      0.81; 3.67 (0.79)), and reflection (alpha = 0.63; 3.68 (0.64)). DISCUSSION: The
      student performance dashboard provides efficient feedback access, yet students'
      use of this information to guide learning is variable. These results can inform
      other programs seeking to foster lifelong learning skills.

PMID- 30187394
TI  - Factor structure and measurement invariance of the Subjective Vitality Scale:
      evidence from Chinese adolescents in Hong Kong.
AB  - PURPOSE: This study translates the Subjective Vitality Scale (SVS) into Chinese
      and examines its factor structure and measurement invariance in a sample of
      Chinese adolescents in Hong Kong. METHODS: Chinese adolescents in Hong Kong were
      invited to participate in the study. Four models of the SVS (a 7-item model, two
      6-item models and a 5-item model) were compared using confirmatory factor
      analysis (CFA). The internal consistency reliability was evaluated using
      Cronbach's alpha coefficients, and the criterion validity was assessed using
      bivariate correlations between subjective vitality and positive and negative
      affect. Finally, measurement invariance across genders and time points was
      examined to evaluate the invariance of the SVS model. RESULTS: The results of the
      CFA analysis indicated that the 5-item measurement model fit the data better than
      the other three models. The Cronbach's alpha was above 0.70 (0.92), revealing
      excellent internal consistency reliability, and the SVS was significantly
      associated with positive affect and negatively associated with negative affect,
      indicating criterion validity. Finally, the measurement invariance analysis of
      the 5-item model displayed strict invariance across genders and time points.
      CONCLUSIONS: The results support the 5-item measurement model of the Chinese
      version of the SVS. This model has excellent internal consistency reliability,
      supports the criterion validity of the instrument and demonstrates strict
      invariance across genders and time points. In summary, the findings suggest that
      the 5-item Chinese version of the SVS is a reliable and valid instrument for
      assessing the subjective vitality of Chinese adolescents in Hong Kong.

PMID- 30187393
TI  - Modification of existing patient-reported outcome measures: qualitative
      development of the MD Anderson Symptom Inventory for malignant pleural
      mesothelioma (MDASI-MPM).
AB  - PURPOSE: Malignant pleural mesothelioma (MPM) is an aggressive cancer of the lung
      pleura. The MD Anderson Symptom Inventory (MDASI) is a patient-reported outcome
      (PRO) measure of symptom burden, the combined impact of disease-related and
      treatment-related symptoms on functioning. Validated PRO measures may require
      modification for use in specific study populations. We sought to modify the MDASI
      for patients with MPM and create a fit-for-purpose symptom-burden measure for use
      in a clinical trial, according to US Food and Drug Administration guidance on PRO
      utilization to support labeling claims. METHODS: A literature review for MPM
      symptoms was conducted. Patients with MPM were qualitatively interviewed about
      experiences of disease and treatment. Descriptive analysis identified symptoms
      and interference with functioning to define MPM-related symptom burden. An expert
      panel rated the relevance of identified symptoms to patients with MPM. Patients
      who received the investigational drug in a previous Phase I study were
      interviewed for drug-specific symptoms. RESULTS: Literature review and interviews
      of 20 patients identified 31 MPM-related symptoms. A conceptual model of MPM
      related symptom burden was developed. After expert-panel relevance review, five
      MPM-specific items and the 13 core MDASI symptoms met criteria for inclusion in a
      provisional MDASI-MPM for psychometric testing. Interviews with six patients
      identified six drug-specific symptoms; three were mentioned by multiple patients.
      Of these three, one was not in the core MDASI. CONCLUSIONS: The MDASI-MPM has
      established content validity and, with the addition of one symptom item, is ready
      for psychometric testing as fit-for-purpose for a clinical trial of an
      investigational agent.

PMID- 30187395
TI  - Health-related quality of life in people with advanced dementia: a comparison of
      EQ-5D-5L and QUALID instruments.
AB  - BACKGROUND: Assessing health-related quality of life (HRQOL) in people with
      advanced dementia is challenging but important for informed decision-making.
      Proxy measurement of this construct is difficult and is often rated lower than
      self-report. Accurate proxy rating of quality of life in dementia is related to
      identification of concepts important to the person themselves, as well as the
      sensitivity of the measures used. The main aim of this study was to compare the
      performance of two instruments-QUALID and EQ-5D-5L-on measuring HRQOL in people
      with advanced dementia. METHODS: In a sub-study nested within a cluster-RCT we
      collected proxy(nurse)-completed EQ-5D-5L and QUALID measures at baseline, 3, 6,
      9 and 12 months' follow-up for people with advanced dementia, residing in 20
      nursing homes across Australia. Spearman's rank correlations, partial
      correlations and linear regressions were used to assess the relationship between
      the HRQOL instrument scores and their changes over time. RESULTS: The mean weight
      from 284 people for the EQ-5D-5L and QUALID at baseline were 0.004 (95% CI -
      0.026, 0.033) and 24.98 (95% CI 24.13, 25.82), respectively. At 12 months' follow
      up, 115 participants remained alive. EQ-5D-5L weights and QUALID scores at
      baseline and at follow-up were moderately correlated (r = - 0.437; p < 0.001 at
      12 months). Changes within QUALID and EQ-5D-5L across the same follow-up periods
      were also correlated (r = - 0.266; p = 0.005). The regression analyses support
      these findings. CONCLUSION: Whilst these quality of life instruments demonstrated
      moderate correlation, the EQ-5D-5L does not appear to capture all aspects of
      quality of life that are relevant to people with advanced dementia and we cannot
      recommend the use of this instrument for use within this population. The QUALID
      appears to be a more suitable instrument for measuring HRQOL in people with
      severe dementia, but is not preference-based, which limits its application in
      economic evaluations of dementia care.

PMID- 30187396
TI  - Correction to: Contextual modulation of prime response retrieval processes:
      Evidence from auditory negative priming.
AB  - The Publisher regrets that two erroneous values were introduced by the typesetter
      when performing proof corrections.

PMID- 30187397
TI  - Listening back in time: Does attention to memory facilitate word-in-noise
      identification?
AB  - The ephemeral nature of spoken words creates a challenge for oral communications
      where incoming speech sounds must be processed in relation to representations of
      just-perceived sounds stored in short-term memory. This can be particularly
      taxing in noisy environments where perception of speech is often impaired or
      initially incorrect. Usage of prior contextual information (e.g., a semantically
      related word) has been shown to improve speech in noise identification. In three
      experiments, we demonstrate a comparable effect of a semantically related cue
      word placed after an energetically masked target word in improving accuracy of
      target-word identification. This effect persisted irrespective of cue modality
      (visual or auditory cue word) and, in the case of cues after the target, lasted
      even when the cue word was presented up to 4 seconds after the target. The
      results are framed in the context of an attention to memory model that seeks to
      explain the cognitive and neural mechanisms behind processing of items in
      auditory memory.

PMID- 30187398
TI  - Visual perspective taking for avatars in a Simon task.
AB  - In modern digital applications, users often interact with virtual representations
      of themselves or others, called avatars. We examined how these avatars and their
      perspectives influence stimulus-response compatibility in a Simon task.
      Participants responded to light/dark blue stimuli with left/right key presses in
      the presence of a task-irrelevant avatar. Changes in stimulus-response
      compatibility were used to quantify changes in the mental representation of the
      task and perspective taking toward this avatar. Experiments 1 and 2 showed that
      perspective taking for an avatar occurred in orthogonal stimulus-response
      mappings, causing a compatibility effect from the avatar's point of view. In the
      following two experiments we introduced a larger variety of angular disparities
      between the participant and avatar. In Experiment 3, the Simon effect with
      lateralized stimulus positions remained largely unaffected by the avatar,
      pointing toward an absence of perspective taking. In Experiment 4, after avatar
      hand movements were added in order to strengthen the participants' sense of
      agency over the avatar, a spatial compatibility effect from the avatar's
      perspective was observed again, and hints of the selective use of perspective
      taking on a trial-by-trial basis were found. Overall, the results indicate that
      users can incorporate the perspective of an avatar into their mental
      representation of a situation, even when this perspective is unnecessary to
      complete a task, but that certain contextual requirements have to be met.

PMID- 30187399
TI  - Human-Scale Liver Harvest and Decellularization for Preclinical Research.
AB  - Decellularized scaffolds are promising for organ regeneration; to facilitate
      analyses of decellularization and preclinical research, experiments using large
      animals are indispensable. An efficient protocol using large animals requires the
      modification of current methods to account for differences in anatomy, size,
      stiffness, and animal handling. This chapter describes a method for the
      decellularization of livers from large animals (especially porcine livers),
      including anesthesia, organ harvest, organ decellularization, and storage, with a
      summary of potential pitfalls. This methodology can hypothetically be applied to
      large animals for preclinical studies and subsequent clinical applications.

PMID- 30187400
TI  - Reconstruction of Regenerative Stem Cell Niche by Cell Aggregate Engineering.
AB  - The niche plays critical roles in regulating functionality and determining
      regenerative outcomes of stem cells, for which establishment of favorable
      microenvironments is in demand in translational medicine. In recent years, the
      cell aggregate technology has shown immense potential to reconstruct a beneficial
      topical niche for stem cell-mediated regeneration, which has been recognized as a
      promising concept for high-density stem cell delivery with preservation of the
      self-produced, tissue-specific extracellular matrix microenvironments. Here, we
      describe the basic methodology of stem cell aggregate-based niche engineering and
      quality check indexes prior to application.

PMID- 30187401
TI  - Differentiation of Menstrual Blood Stem Cells into Keratinocyte-Like Cells on
      Bilayer Nanofibrous Scaffold.
AB  - Skin tissue engineering is a high-throughput technology to heal the wounds.
      Already, considerable advances have been achieved using stem cells for wound
      healing applications. Menstrual blood stem cell (MenSC) is an available and
      accessible source of stem cells that have differentiation potential into a wide
      range of lineages like keratinocytes. Extracellular matrix like substratum plays
      an impressive role in skin regeneration as an attachment site for stem cells by
      transmitting the bioactive signals and provoking stem cells to differentiate into
      keratinocyte lineage. The biomimetic nanofibrous scaffold especially in bilayer
      format has been extensively utilized to develop skin equivalents. This chapter
      explains detailed protocols of keratinocyte differentiation of MenSCs on bilayer
      scaffold comprising amniotic membrane and fibroin nanofibers. The isolated MenSCs
      are seeded on the nanofibers and subsequently differentiated into keratinocyte
      lineage in co-culture with foreskin-derived keratinocytes. Immunofluorescence
      staining is used to evaluate the development of seeded MenSCs in bilayer scaffold
      into keratinocyte-like cells.

PMID- 30187402
TI  - Heavy metal leaching and plant uptake in mudflat soils amended with sewage
      sludge.
AB  - The leaching and uptake of Cd, Cu, Pb, and Zn by maize (Zea mays L.) in mudflat
      saline-alkali soils amended by sewage sludge was examined using a greenhouse
      leaching column experiment. Application of sewage sludge caused decreased pH,
      increased DOC, and increased Cd, Cu, Pb, and Zn concentrations in leachates. The
      similar temporal dynamics of DOC and the metal concentrations in leachates
      suggested complexation of the metals with DOC. There was downward movement of
      metals as evidenced by the metal enrichment in the bottom layer (20-40-cm depth)
      of leaching columns (p < 0.05). The enrichment of metals was contributed by the
      acid-soluble/exchangeable fraction (EX), reducible fraction (RG), oxidizable
      fraction (OXI), and residual fraction (RES), indicating redistribution of leached
      metals from the top 20-cm layer. The sewage sludge application also enhanced
      plant uptake of metals. However, even under the greatest sludge application rate
      (150 g kg-1), very small proportions, averagely 0.65% and 0.35%, of the applied
      metals were leached and taken up by maize, respectively, over the experimental
      period. Long-term field-scale research is warranted for further investigation of
      the effects of sewage sludge amendment on heavy metal fractionation and
      distribution in mudflat soil-plant-water system.

PMID- 30187403
TI  - Radiostrontium transport in plants and phytoremediation.
AB  - Radiostrontium is a common product of nuclear fission and was emitted into the
      environment in the course of nuclear weapon tests as well as from nuclear reactor
      accidents. The release of 90Sr and 89Sr into the environment can pose health
      threats due to their characteristics such as high specific activities and easy
      access in human body due to its chemical analogy to calcium. Radiostrontium
      enters the human food chain by the consumption of plants grown on sites
      comprising fission-derived radionuclides. For humans, Sr is not an essential
      element, but, due to solubility in water and homology with calcium, once interred
      in the body, it gets deposited in bones and in teeth. This concern has drawn the
      attention of researchers throughout the globe to develop sustainable treatment
      processes to remediate soil and water resources. Nowadays, phytoremediation has
      become a promising approach for the remediation of large extents of toxic heavy
      metals. Some of the plants have been reported to accumulate Sr inside their
      biomass but detailed mechanisms at genetic level are still to be uncovered.
      However, there is inadequate information offered to assess the possibility of
      this remediation approach. This review highlights phytoremediation approach for
      Sr and explains in detail the uptake mechanism inside plants.

PMID- 30187404
TI  - Environmental exposure of anthropogenic micropollutants in the Prut River at the
      Romanian-Moldavian border: a snapshot in the lower Danube river basin.
AB  - The Prut River, the second longest tributary of the Danube river, was
      investigated for a wide range of anthropogenic organic pollutants to fill the
      data gap on environmental contamination in eastern European surface waters. In
      this study, the occurrence of a wide range of organic pollutants was measured
      along the transboundary Prut River, between Sculeni and Branza in 2010-2012.
      Using two different analytical methods, gas chromatography coupled to mass
      spectrometry and liquid chromatography coupled to high-resolution mass
      spectrometry, over 300 compounds were screened for and 88 compounds were
      determined in the Prut River. In general, the chemicals occurred at low levels.
      At the last sampling site upstream of the confluence with the Danube river at
      Branza, the highest average concentrations (>= 100 ng L-1) were determined for
      the artificial sweetener acesulfame, the pharmaceuticals metformin, 4
      acetamidoantipyrene, and 4,4,5,8-tetramethylchroman-2-ol, the antioxidants 2,4-di
      tert-butylphenol, 3-tert-butyl-4-hydroxyanisol, and 3,5-di-tert-butyl-4-hydroxy
      toluene, the personal care products HHCB (galaxolide), 4-phenyl-benzophenone, and
      octyl dimethyl-p-aminobenzoic acid, the industrial chemical diphenylsulfone, and
      the sterol cholesterol. Low concentrations of agricultural pesticides occurred in
      the catchment. At Branza, the total accumulated load of all measured compounds
      was calculated to be almost 19 kg day-1. In comparison to the Rhine River, the
      loads in the Prut, determined with same LC-HRMS method for the same set of
      analytes, were two orders of magnitude lower. Discharge of wastewater without
      proper treatment from the city of Iasi in the Jijia catchment (Romania) as well
      as from the city of Cahul (Moldova) revealed a distinct increase in
      concentrations and loads in the Prut at Frasinesti and Branza. Thus, an
      implementation of wastewater treatment capacities in the Prut River basin would
      considerably reduce the loads of micropollutants from urban point sources.

PMID- 30187405
TI  - Application of magnesium peroxide (MgO2) nanoparticles for toluene remediation
      from groundwater: batch and column studies.
AB  - In the present study, magnesium peroxide (MgO2) nanoparticles were synthesized by
      electro-deposition process and characterized by X-ray diffraction (XRD) and field
      emission scanning electron microscopy (FESEM). The batch experiments were
      conducted to evaluate the MgO2 half-life (600 mg/L) in groundwater under various
      temperatures (4, 15, and 30  degrees C) and initial pH (3, 7, and 12). The effect
      of Fe2+ ions (enhanced oxidation) on the toluene remediation by MgO2 was also
      investigated. Nanoparticles were injected to sand-packed continuous-flow columns,
      and toluene removal (50 ppm) was studied within 50 days at 15  degrees C. The
      results indicated that the half-life of MgO2 at pH 3 and 12 were 5 and 15 days,
      respectively, in comparison to 10 days at the initial pH 7 and 15  degrees C. The
      nanoparticles showed 20 and 7.5 days half-life at 4 and 30  degrees C
      temperatures, respectively. Injection of Fe2+ ions indicated an impressive effect
      on toluene removal by MgO2, and the contaminant was completely removed after 5
      and 10 days, in the batch and column experiments, respectively. Confocal laser
      scanning microscope (CLSM) analysis indicated that the attached biofilm had a
      significant role in the decontamination of groundwater. Comparison of
      bioremediation and enhanced oxidation resulted in a considerable insight into the
      application of magnesium peroxide in groundwater remediation. Graphical abstract
      ?.

PMID- 30187406
TI  - A systematic review of financial implications of air pollution on health in Asia.
AB  - Economic losses due to health-related implications of air pollution were huge and
      incurred significant burdens towards healthcare providers. The objective of this
      study is to systematically review published literature on the financial
      implications of air pollution on health in Asia. Four databases: PubMed, Scopus,
      NHS Economic Evaluation Database (NHS EED), and Web of Science (WoS) were used to
      identify all the relevant articles. It was limited to all articles that had been
      published in the respected databases from January 2007 until March 2017. Twenty
      four articles were included in this review. Five of the 24 studies (20.8%)
      reported financial implications of air pollution-related disease through value of
      statistical life (VOSL) which ranged from USD180 million to USD2.2 billion, six
      (25%) studies used cost of illness (COI) to evaluate air pollution-related
      morbidity and found that the cost ranged from USD5.4 million to USD9.1 billion.
      Another six studies (25%) used a combination of VOSL and COI for both mortality
      and morbidity valuation and found that the financial implications ranging from
      USD253 million to USD2.9 billion. Thirteen (54.2%) studies reported healthcare
      cost associated with both hospital admission and outpatient visit, five (20.1%)
      on hospital admission only, and one (4.2%) on outpatient visit only. Economic
      impacts of air pollution can be huge with significant deterioration of health
      among the Asians.

PMID- 30187407
TI  - Earthworms as plug flow reactors: a first-order kinetic study on the gut of the
      vermicomposting earthworm Eudrilus eugeniae.
AB  - Earthworms are commonly referred as environmental engineers and their guts are
      often compared with chemical reactors. However, modeling experiments to
      substantiate it are lacking. The aim of this study was to use established reactor
      models, particularly PFR, on the gut of the vermicomposting earthworm Eudrilus
      eugeniae to understand more on its digestion. To achieve the objective, a
      mathematical model based on first-order kinetics was framed and used to determine
      the pattern of digestion rates of nutrient indicators, namely total carbon (%),
      total nitrogen (%), C/N ratio, 13C (0/00), and 15N (0/00) at five intersections
      (pre-intestine, foregut, midgut A, midgut B, and hindgut) along the gut of E.
      eugeniae. The experimental results revealed that the concentrations of TC, TN,
      13C, and 15N decreased during gut transit, whereas C/N ratio increased. The first
      order model demonstrated that all the nutrients exhibit a linear pattern of
      digestion during gut transit, which supports the PFR model. On this basis, the
      present study concludes that the gut of E. eugeniae functions as PFR.

PMID- 30187408
TI  - Levels and sources of organic compounds in fine ambient aerosols over National
      Capital Region of India.
AB  - The study presents the spatial and temporal variation of fine ambient aerosols
      (PM2.5) over National Capital Region (NCR), India, during January to June 2016.
      The investigation includes three sampling sites, one in Delhi and two in the
      adjoining states of Delhi (Uttar Pradesh and Haryana), across NCR, India. The
      average PM2.5 concentration was highest for Delhi (128.5 +/- 51.5 MUg m-3) and
      lowest for Mahendragarh, Haryana (74.5 +/- 28.7 MUg m-3), during the study
      period. Seasonal variation was similar for all the sites with highest
      concentration during winter and lowest in summer. PM2.5 samples were analysed for
      organic compounds using gas chromatograph (GC). The concentration of three
      organic compound classes, n-alkanes (C11-C35), polycyclic aromatic hydrocarbons
      (PAHs), and phthalates, present in PM2.5 samples has been reported. Diagnostic
      ratios for n-alkanes demonstrated that biogenic emissions were dominant over
      Mahendragarh while major contributions were observed from petrogenic emissions
      over Delhi and Modinagar, Uttar Pradesh. Molecular diagnostic ratios were
      calculated to distinguish between different sources of PAHs, which revealed that
      the fossil fuel combustion (diesel and gasoline emissions), traffic emissions,
      and biomass burning are the major source contributors. Health risk associated
      with human exposure of phthalates and PAHs was also assessed as daily intake (DI,
      ng kg-1 day-1) and lung cancer risk, respectively. Backward trajectory analysis
      explained the local, regional, and long-range transport routes of PM2.5 for all
      sites. Principal component analysis (PCA) results summarized that the vehicular
      emissions, biomass burning, and plastic burning were the major sources of the
      PAHs and phthalates over the sampling sites.

PMID- 30187410
TI  - The effect of cellulose production waste and municipal sewage sludge on biomass
      and heavy metal uptake by a plant mixture.
AB  - Environmental management of cellulose production waste and municipal sewage
      sludge appears to be substantiated due to various physicochemical properties of
      these wastes. The aim of the conducted research was to determine the effect of
      cellulose production waste and sewage sludge on yielding and heavy metal uptake
      by a plant mixture. The research was conducted under field experiment conditions,
      determining the fertilizer value of these wastes in the environmental aspect. The
      research was carried out in the years 2013-2016. Species composition of the plant
      mixture was adjusted to habitat conditions. It was established that, as compared
      with the cellulose production waste, the municipal sewage sludge used in the
      experiment had a higher content of macroelements. The content of heavy metals in
      the studied waste did not exceed the limits that condition their use in
      agriculture and reclamation. Applying only the cellulose production waste did not
      significantly decrease the yield of the plants. Municipal sewage sludge showed
      the highest yield-forming effect. Mixing the above-mentioned wastes and their
      application to soil had a significant effect on the increase in the plant mixture
      yield. The waste applied to soil also increased the content of Cr, Cd, Pb, Cu,
      and Zn in the plant mix. The level of heavy metal content in the plant mix did
      not exclude this biomass from being used for fodder or reclamation purposes. The
      cellulose production waste and municipal sewage sludge increased the heavy metal
      uptake by the plant mixture. The plant biomass extracted heavy metals from the
      sewage sludge more intensively than from the cellulose production waste. Among
      the analyzed heavy metals, the highest phytoremediation was recorded for Ni
      (30%), followed by Cd (20%), Cr (15%), Pb (10%), and the lowest for Cu (9%) and
      Zn (8%). Application of the cellulose production waste and sewage sludge to soil
      also increased the content of the studied heavy metals in soil. However, it did
      not cause deterioration of soil quality standards. Heterogeneity in the chemical
      composition of the wastes confirms that each batch intended to be used for
      environmental management should be subjected to chemical control.

PMID- 30187409
TI  - Photochemical oxidation of di-n-butyl phthalate in atmospheric hydrometeors by
      hydroxyl radicals from nitrous acid.
AB  - The photochemical oxidation of di-n-butyl phthalate (DBP) by *OH radicals from
      nitrous acid (HONO) in atmospheric hydrometeors was explored by two techniques,
      steady-state irradiation, and laser flash photolysis (LFP). The effects of
      atmospheric liquid parameters on DBP transformation were systematically
      evaluated, showing that DBP does not react with HONO directly and *OH-initiated
      reactions are crucial steps for consumption and transformation of DBP. Two
      reaction channels are operative: *OH addition and hydrogen atom abstraction. The
      overall rate constant for the reaction of DBP with *OH is 5.7 * 109 M-1 s-1, and
      its specific rate constant for addition is 3.7 * 109 M-1 s-1 determined by using
      laser flash photolysis technique. Comparing the individual reaction rate constant
      for aromatic ring addition with the total rate constant, the majority of the *OH
      radicals (about 65%) attack the aromatic ring. The major transformation products
      were identified by GC-MS, and the trends of their yields derived from both ring
      addition and H-abstraction with time are discussed. These results provide
      important insights into the photochemical transformation of DBP in atmospheric
      hydrometeors and contribute to atmospheric aerosol chemistry.

PMID- 30187411
TI  - Highly efficient treatment of real benzene dye intermediate wastewater by simple
      limestone and lime neutralization-coagulation with improved Fenton oxidation.
AB  - Multistage Fenton oxidation is a favored method for the treatment of benzene dye
      intermediate (BDI) wastewater, but the pH adjustments required after each stage
      of the Fenton process with a simple way is still a challenge. Limestone
      pretreatment and lime neutralization-coagulation were used to solve the problem
      in multistage Fenton process. First, we determined the optimal conditions of
      Fenton oxidation using the Box-Behnken response surface method. Limestone
      pretreatment before the multistage Fenton process allowed for simultaneous pH
      adjustment and 14.15% COD removal. Most notably, the lime cream neutralization
      coagulation process effectively adjusted the pH after each stage of the Fenton
      process. The optimum CaO particle size, lime mass fraction, mixing time, and
      stirring speed were determined by orthogonal tests. COD removal (89.23%) was
      obtained when lime cream neutralization-coagulation was applied to the three
      staged Fenton process, while only 58.57% COD removal was obtained by the
      unadjusted single-staged Fenton process. The COD and wastewater color were
      reduced from 10,600 mg/L and 12,200 multiples to 495 mg/L and 20 multiples,
      respectively, using the adjusted process. This improved method provides a
      promising cost-effective way to efficiently treat real BDI wastewater.

PMID- 30187412
TI  - Effect of distillery spentwash fertigation on crop growth, yield, and
      accumulation of potentially toxic elements in rice.
AB  - The safe disposal of industrial effluents always remained a challenging process
      because of their high level of nutrients, toxic elements, and salts. A pot
      experiment was conducted to investigate the effects of various concentrations
      (5%, 10%, 15%, and 20%) of sugar industry effluent spentwash (SW) fertigated with
      tab water (TW), on soil properties, crop growth, physiological parameters, yield
      components, and accumulation of potentially toxic elements (PTEs) in rice (Oryza
      sativa L.) grains and straw. The results showed that soil physico-chemical
      properties were modified with rise in SW concentration. Application of 5% SW
      significantly enhanced the plant growth, and yield components. Photosynthesis
      rate, transpiration rate, and stomatal conductance were significantly higher
      under 5% SW concentration in comparison with control. However, SW concentrations
      of > 5% showed inhibitory effects for all growth, physiological, and yield
      components. Accumulation of PTEs showed increasing trend with rise in SW
      concentration. However, under 5% SW concentration, all the PTEs in rice grain and
      straw were within the permissible limits (PLs) recommended by FAO/WHO and no
      health hazards were detected by health risk assessment. Based on the study
      results, 5% SW fertigation with TW can be applied as fertilizer for enhancing the
      growth and productivity of rice. Graphical abstract.

PMID- 30187413
TI  - Magnetic biochar-based manganese oxide composite for enhanced fluoroquinolone
      antibiotic removal from water.
AB  - Magnetic biochar-based manganese oxide composite (MMB) and raw biochar (BC) were
      synthesized via pyrolysis at a temperature of 500  degrees C under anoxic
      conditions of potato stems and leaves, characterized, and successfully used for
      the removal of norfloxacin (NOR), ciprofloxacin (CIP), and enrofloxacin (ENR) as
      representative compounds of fluoroquinolone antibiotics (FQs). Characterization
      results suggested that Fe3O4 and MnOx are the dominant crystals in MMB. MMB
      possessed large surface area and pore volume than BC. Batch adsorption
      experiments showed that the maximum adsorption abilities of MMB for norfloxacin
      (NOR), ciprofloxacin (CIP), and enrofloxacin (ENR) were 6.94, 8.37, and 7.19 mg g
      1. In comparison to BC, the adsorption abilities of MMB increased 1.2, 1.5, and
      1.6 times for NOR, CIP, and ENR, respectively. The pseudo-second-order kinetic
      model and the Langmuir model correlated satisfactorily to the experimental data.
      Thermodynamic studies revealed that the adsorption processes were spontaneous and
      endothermic. The adsorption capacity of MMB decreased with increasing solution pH
      (between 3.0 and 10.0) and increasing ionic strength (0.001-0.1). The MMB with
      high FQ removal efficiency, easy separation, and desirable regeneration ability
      may have promising environmental applications for the removal of fluoroquinolone
      antibiotics from water environment.

PMID- 30187414
TI  - Physiological characterization of common bean (Phaseolus vulgaris L.) under
      abiotic stresses for breeding purposes.
AB  - In the Brazilian wet and dry seasons, common beans (Phaseolus vulgaris L.) are
      grown under rainfed conditions with unexpected episodes of drought and high
      temperatures. The objective of this study was to evaluate the physiological
      mechanisms associated with drought adaptation traits in landraces and
      line/cultivars of beans from the Andean and Mesoamerican gene pools. Twenty-five
      genotypes, contrasting in terms of drought tolerance, were evaluated in a
      phenotyping platform under irrigated and rainfed conditions. Agronomic and
      physiological parameters such as grain yield, shoot structures, gas exchange,
      water potential, and osmotic adjustment were evaluated. The stress intensity was
      estimated to be 0.57, and the grain yield reduction ranged from 22 to 89%. Seven
      accessions, representative of the Andean and Mesoamerican germplasm (CF 200012,
      CF 240056, CF 250002, CF 900004, CNF 4497, CNF 7382, and SEA 5), presented
      superior performance in grain yield with and without stresses. The physiological
      responses under abiotic stresses were highly variable among the genotypes, and
      two Mesoamerican accessions (CF 200012 and SEA 5) showed more favorable adaptive
      responses. As the main secondary physiological traits, gas exchange and osmotic
      adjustment should be evaluated together with the grain yield to increase the
      selection efficiency of abiotic stresses-tolerant common bean lines.

PMID- 30187415
TI  - Evaluation of (-)-borneol derivatives against the Zika vector, Aedes aegypti and
      a non-target species, Artemia sp.
AB  - Zika, dengue, and chikungunya are vector-borne diseases of pronounced concern
      transmitted by the mosquito Aedes aegypti Linn. (Diptera: Culicidae). The most
      important method to avoid outbreaks is to control mosquito spreading by the
      employment of insecticides and larvicides. Failure to control mosquito dispersal
      is mostly accounted to Ae. aegypti resistance to currently available larvicides
      and insecticides, encouraging the development of novel pesticides. In addition,
      the excessive use of larvicides poses serious threats to human health and the
      environment. Evaluation of natural products as larvicides in an attempt to
      overcome this situation is often found in the literature because products
      originated from nature are considered less toxic to non-target species and more
      eco-friendly. (-)-Borneol is a bicyclic monoterpene present in essential oils
      with moderate larvicidal activity. On account of these facts, it was of our
      interest to synthesize (-)-borneol ester derivatives aiming to study its
      structure-activity relationships against Ae. aegypti larvae. With the goal to
      estimate toxicity to a non-target species, evaluation of the lethal concentration
      50% (LC50) on Artemia sp. (Artemiidae) and calculation of selectivity towards Ae.
      aegypti were carried out. The most potent derivative, (-)-Bornyl chloroacetate,
      exhibited the highest suitability index, demonstrating lower environmental
      toxicity than other borneol ester derivatives. A parabolic relationship between (
      )-borneol esters larvicidal activity and partition coefficient (Log P) was
      achieved and a correlation equation obtained, validating the importance of
      lipophilicity to the larvicidal activity of these compounds.

PMID- 30187416
TI  - Selenium application alters soil cadmium bioavailability and reduces its
      accumulation in rice grown in Cd-contaminated soil.
AB  - Selenium (Se) alleviates cadmium (Cd) accumulation in several plants.
      Nevertheless, it is still unclear why it has such effect. Thus, this study aimed
      to investigate the effects of Se on soil Cd bioavailability, and Cd accumulation
      in flooded rice plants, and to determine the mechanisms underlying these effects.
      Concentration of Cd and Se in different rice tissues was determined along Cd and
      Se concentrations in the soil solution and soil Cd fractions. Results showed that
      exogenous selenite and selenate treatments significantly increased rice grain Se
      by 4.25- and 2.39-fold and decreased Cd by 36.5% and 25.3% relative to control
      treatment, respectively. The addition of Se to Cd-contaminated soil significantly
      decreased total Cd concentration in the soil solution by 11.2-13.0%, increased
      soil pH by 0.06-0.32 units, and enhanced soil Cd immobilization in relation to
      control. Exogenous Se also reduced diethylenetriaminepentaacetic acid-Cd,
      exchangeable, and residual Cd but increased the levels of Cd bound to carbonate
      and iron and manganese oxides. Thus, amending Cd-contaminated soil with Se may
      help decrease Cd content as well as increase Se levels in rice grain, as Se may
      mitigate Cd accumulation in rice plants by increasing soil pH, reducing Cd
      bioavailability, and inhibiting Cd translocation from roots to shoots.

PMID- 30187418
TI  - Estimation of formaldehyde occupational exposure limit based on genetic damage in
      some Iranian exposed workers using benchmark dose method.
AB  - The present study evaluated an occupational exposure level for formaldehyde
      employing benchmark dose (BMD) approach. Dose-response relationship was
      determined by utilizing cumulative occupational exposure dose and DNA damage.
      Based on this goal, outcome of comet assay for some Iranian exposed people in
      occupational exposure individuals was used. In order to assess formaldehyde
      exposure, 53 occupationally exposed individuals selected from four melamine
      tableware workshops and 34 unexposed subjects as a control group were examined.
      The occupational exposure dose was carried out according to the NIOSH-3500
      method, and the DNA damage was obtained by employing comet assay in peripheral
      blood cells. EPA Benchmark Dose Software was employed for calculating BMD and
      BMDL. Cumulative exposure dose of formaldehyde was between of 2.4 and 1972 mg.
      According to the findings of the current study, the induction of DNA damage in
      the exposed persons was increased tail length and tail moment (p < 0.001), when
      compared to controls. Finally, an acceptable dose-response relationship was
      obtained in three-category information between formaldehyde cumulative exposure
      doses and genetic toxicity. BMDL was 0.034 mg/m3 (0.028 ppm), corresponding to
      genetic damage of peripheral blood cells. It can be concluded that the
      occupational permissible limit in Iranian people could be at levels lower than
      OSHA standards.

PMID- 30187419
TI  - Physical and Mental Impact of Laparoscopic Sleeve Gastrectomy on the Surgeon:
      French vs. American Positions. A Randomized and Controlled Study.
AB  - PURPOSE: To determine the physical and mental impact on the primary surgeon, by
      the patient's and surgical staff's dispositions at the operating table, during
      laparoscopic vertical sleeve gastrectomy. MATERIALS AND METHODS: This is a
      randomized and controlled study that included 18 laparoscopic sleeve gastrectomy
      procedures performed by two surgeons in a private and academic hospital. The
      cases were randomized for the American or French position. After surgery, the
      National Aeronautics and Space Administration - Task Load Index (NASA-TLX) and
      the Body Part Discomfort (BPD) scales were applied to the primary surgeon.
      RESULTS: An increased workload and more discomfort were reported when using the
      French position. The NASA-TLX was 28 +/- 8 vs. 57 +/- 18 (p = 0.001), and the BPD
      was 2 vs. 8 (p = 0.001). CONCLUSIONS: The American position resulted in a lower
      physical and mental impact on the surgeon when performing a laparoscopic sleeve
      gastrectomy.

PMID- 30187417
TI  - A review on removal of siloxanes from biogas: with a special focus on volatile
      methylsiloxanes.
AB  - The occurrence of siloxanes is a major barrier to use of biogas as renewable
      energy source, and removal of siloxanes from biogas before combustion is needed.
      The siloxane can be transformed into silicon dioxide (SiO2) through the
      combustion process in engine, which will be deposited on the spark plug,
      cylinder, and impeller to form the silica layer, causing the wear and damage of
      the engine parts, and shorten the life of the engine and affect the utilization
      efficiency of the biogas. This paper reviewed some methods and technologies for
      siloxanes removal from biogas. There are three commercial available technologies
      to remove siloxanes: adsorption, absorption, and cryocondensation. Other newer
      technologies with better prospects for development also have made a research
      progress, including membrane, catalysts, biotrickling filters. This work
      introduces the source and characterization of siloxanes in biogas, reviews the
      scientific progress of siloxanes removal, and discusses the development direction
      and further research of removal siloxanes.

PMID- 30187420
TI  - Macroscopic Evaluation of Gastric Specimens After Laparoscopic Sleeve Gastrectomy
      an Optimum Screening Test for Incidental Pathologies?
AB  - INTRODUCTION: Obesity is a serious lifestyle disease with various comorbidities
      and an augmented risk of cancer. Laparoscopic sleeve gastrectomy (LSG) has
      recently become the most popular bariatric procedure worldwide. While the cost
      effectiveness is a major healthcare providers' concern, the point of histological
      exam of each resected tissue may be questioned. MATERIAL/METHODS: We
      prospectively included patients who underwent LSG. Before the surgery,
      gastroscopy and abdominal sonography were performed to exclude malignancies. The
      gastric specimen was cut open after the surgery and inspected macroscopically,
      then sent for a microscopic examination. RESULTS: In 5 cases out of 115,
      macroscopic evaluation of the resected specimen performed by the surgeon
      suggested existing pathology, confirmed by a microscopic evaluation in 3 out of 5
      cases. In the remaining 2 cases, pathological analysis did not reveal
      abnormalities. In 110 cases, the gastric specimen was recognized to be unchanged
      by the surgeon, 109 out of which were confirmed by the pathologist to be normal,
      in 1 case a hyperplastic polyp was found. The sensitivity of macroscopic
      evaluation reached 75% (95% CI, 19.4-99.4%, p = 0.625), with specificity of 98.2%
      (95% CI, 93.6-99.8%, p < 0.0001), and negative predictive value of 99.1% (95% CI,
      95-99.9%, p < 0.0001). CONCLUSIONS: During LSG, a thorough visual inspection of
      the peritoneal cavity along with a macroscopic surgical evaluation of specimen in
      patients who had preoperative endoscopy with no findings allows to achieve very
      good specificity and good sensitivity. Therefore, this procedure may be useful as
      a screening test for incidental pathologies in bariatric patients and may exclude
      unnecessary histological examination.

PMID- 30187421
TI  - Mentorship Programs in Bariatric Surgery Reduce Perioperative Complication Rate
      at Equal Short-Term Outcome-Results from the OPTIMIZE Trial.
AB  - OBJECTIVES: The aim of this study was to determine the efficacy of coaching on
      outcome in low volume centers of excellence and to evaluate the influence of
      mentorship programs on the center development. BACKGROUND: The number of
      bariatric procedures has increased steadily in the last years. Providing
      nationwide bariatric care on a high professional level needs structures to train
      and guide upcoming centers and ensure high quality in patient care. METHODS: A
      prospective multicentered, observational study including laparoscopic sleeve
      gastrectomies (SG) and Roux-en-Y gastric bypass (RYGB) procedures was performed.
      Twelve emerging bariatric centers were coached by five experienced bariatric
      centers. Surgeons of the mentor centers gave guidance on pre- and postsurgical
      management of their patients including complications and proctored the first
      interventions. The results were compared regarding operative outcomes, percentage
      of excess weight loss, complications, and resolution of comorbidities. RESULTS: A
      total of 214 of 293 patients (73.0%) completed the study. The most frequently
      reported complications were wound infection (4.4%), disorder of emptying
      stomach/new reflux (2.4%), anastomotic leaks, intra-abdominal secondary
      hemorrhage, and dumping syndrome (2.0% each). The mortality rate was zero. We
      found no difference in overall complication rates or resolution of obesity
      related comorbidities when comparing experienced surgeons with less experienced
      surgeons. CONCLUSIONS: Our results suggest that under the conditions of the
      practices of this study, coaching and mentoring were associated with comparable
      outcomes both in experienced and emerging centers. In addition, mentorship
      programs ensure equal outcome quality in terms of improvement of obesity
      associated comorbidities. TRIAL REGISTRATION: NCT Number: NCT01754194 .

PMID- 30187423
TI  - Association Between Super-Super-Obesity and Perioperative Short-Term Outcome in
      Patients Undergoing Bariatric Surgery.

PMID- 30187422
TI  - Whether a Short or Long Alimentary Limb Influences Weight Loss in Gastric Bypass:
      a Systematic Review and Meta-Analysis.
AB  - Roux-en-Y gastric bypass, the most commonly performed procedure in bariatric
      surgery, still lacks a consensus on whether alimentary limb length (ALL)
      influences weight loss. Studies were identified by searching multiple electronic
      databases. Studies with enough data including body mass index (BMI) loss and
      percent excess weight loss (% EWL) were eligible. The statistical analysis was
      performed with Stata 14.0. In total, eight studies with 1714 patients were
      included. The meta-analysis suggested that short ALLs weakened the efficacy of
      Roux-en-Y gastric bypass in terms of BMI loss (standard mean deviation (SMD), -
      0.33 [95% confidence intervals (CI), - 0.60, - 0.05], p = 0.021) with 3 years of
      follow-up and % EWL (SMD, - 0.17 [95% CI, - 0.31, - 0.04], p = 0.013) with 2
      years of follow-up. The subgroup analysis demonstrated that the group with a BMI
      >= 50 kg/m2 had a significant SMD between the use of short and the standard ALLs
      (- 0.71 [95% CI, - 1.07, - 0.35], p = 0.000), while the subgroup with a BMI < 50
      kg/m2 (SMD, - 0.29 [95% CI, - 0.78, 0.20], p = 0.247) did not. Compared with a
      standard ALL (130-150 cm), a short ALL (40-100 cm) may reduce the efficacy of the
      Roux-en-Y gastric bypass surgery, while a long ALL (170-250 cm) did not
      significantly improve the effects in terms of BMI loss and % EWL. In addition, a
      potential view of the meta-analysis indicated patients with a BMI < 50 kg/m2
      might get more benefits with a short ALL, while those patients with a BMI >= 50
      kg/m2 might benefit more from a standard ALL.

PMID- 30187426
TI  - Correction to: Factors associated with short interpregnancy interval among women
      treated with in vitro fertilization.
AB  - The original version of this article unfortunately contained a mistake. The name
      of an investigator was incorrectly listed as M. B. Morton, instead of M. B.
      Brown.

PMID- 30187425
TI  - Perinatal follow-up of children born after preimplantation genetic diagnosis
      between 1995 and 2014.
AB  - PURPOSE: We aim to evaluate the safety of PGD. We focus on the congenital
      malformation rate and additionally report on adverse perinatal outcome. METHODS:
      We collated data from a large group of singletons and multiples born after PGD
      between 1995 and 2014. Data on congenital malformation rates in live born
      children and terminated pregnancies, misdiagnosis rate, birth parameters,
      perinatal mortality, and hospital admissions were prospectively collected by
      questionnaires. RESULTS: Four hundred thirty-nine pregnancies in 381 women
      resulted in 364 live born children. Nine children (2.5%) had major malformations.
      This percentage is consistent with other PGD cohorts and comparable to the
      prevalence reported by the European Surveillance of Congenital Anomalies
      (EUROCAT). We reported one misdiagnosis resulting in a spontaneous abortion of a
      fetus with an unbalanced chromosome pattern. 20% of the children were born
      premature (< 37 weeks) and less than 15% had a low birth weight. The incidence of
      hospital admissions is in line with prematurity and low birth weight rate. One
      child from a twin, one child from a triplet, and one singleton died at 23, 32,
      and 37 weeks of gestation respectively. CONCLUSIONS: We found no evidence that
      PGD treatment increases the risk on congenital malformations or adverse perinatal
      outcome. TRIAL REGISTRATION NUMBER: NCT 2 149485.

PMID- 30187427
TI  - Time-lapse imaging systems in IVF laboratories: a French national survey.
AB  - PURPOSE: Although the clinical value of time-lapse imaging (TLI) systems in in
      vitro fertilization (IVF) cycles is still debated, its prevalence worldwide seems
      to be expanding. The situation of TLI in the USA has been recently surveyed, but
      these results might not be transposable to other countries with different IVF
      regulation and funding such as France. This study evaluated the TLI situation in
      French IVF laboratories. METHODS: An anonymous online cross-sectional survey was
      sent by email to 210 embryologists in September and October 2017. Laboratories,
      demographics, TLI clinical use, purchasing plan, and embryologists' opinions were
      analyzed using logistic regression to calculate odds ratio. RESULTS: Of the 210
      lab directors surveyed, 78 responded (37.1%), 43 (55%) working in private IVF
      laboratories and 35 (45%) in public hospitals. Thirty (38.5%) were TLI users. The
      odds of TLI possession were not statistically different according to laboratory
      sector or size. Most embryologists (n = 21, 70%) used TLI for unselected
      patients. Cost was the main reason given by non-users for not implementing TLI (n
      = 24, 50%). Most respondents were convinced that TLI is superior to standard
      morphology (n = 52, 73.2%) and that TLI improves culture conditions (n = 62,
      84.9%). However, half (n = 39, 54.9%) indicated that evidence was still lacking
      to assert TLI clinical usefulness. CONCLUSION: The prevalence of TLI systems and
      embryologists' opinion in France was slightly different from the American
      situation. The different regulation and funding policy might account for some
      differences in terms of TLI use and perception.

PMID- 30187428
TI  - Effects of Dietary Supplementation of Probiotic Mix and Prebiotic on Growth
      Performance, Cecal Microbiota Composition, and Protection Against Escherichia
      coli O78 in Broiler Chickens.
AB  - The current study conducted to investigate the effects of a multi-strain
      commercial probiotic mix and prebiotic (isomaltooligosaccharide, IMO) on broiler
      performance parameters, cecal microbiota composition, and protection against
      challenge with avian pathogenic Escherichia coli (APEC) O78. For this purpose,
      101-day-old Cobb chicks were randomly allocated into four experimental groups (G)
      G01: basal diet, G02: basal diet and challenged with E. coli O78 at 28 days old,
      G03: basal diet with probiotic mix and challenged with E. coli O78 at 28 days
      old, and G04: basal diet with IMO and challenged with E. coli O78 at 28 days old.
      Results showed that weekly body weights in G03 were heavier (P < 0.05) than those
      of G01 and G02 at the fourth and fifth week. The body gain at the fourth and
      fifth week was higher (P < 0.05) in G03 than those of the other groups. The hot
      carcass weight (g) was significantly higher in broiler chickens kept in G03 and
      G04 compared with those in the control groups (G01 and G02). The probiotic mix
      and IMO significantly increased the total lactobacilli and total lactobacilli
      enterococci populations in the ceca of treated broilers, respectively compared
      with those in the control groups. The treated broilers (G03 and G04) also showed
      lower mortality percentage and E. coli recovery rates the liver and spleen than
      those in G02. It was concluded that probiotic mix or IMO significantly improved
      the growth performance and modulated the intestinal microbiota of broiler
      chickens challenged with APEC O78.

PMID- 30187429
TI  - Effect of the EM Bokashi(r) Multimicrobial Probiotic Preparation on the Non
      specific Immune Response in Pigs.
AB  - The aim of the study was to determine the effect of EM Bokashi(r) on the
      phagocytic activity of monocytes and granulocytes, oxidative burst, SWC3, and
      CD11b + CD18+ expression on monocytes and granulocytes, and the serum
      concentration of cytokine and lysozyme in pig. 60 Sixty female piglets were
      divided into two groups: I - control and II - experimental. For the experimental
      group, a probiotic in the form of the preparation EM Bokashi(r) was added to the
      basal feed. Flow cytometry was used to determine selected non-specific immune
      response parameters, intracellular production of hydrogen peroxide by peripheral
      granulocytes and monocytes, and surface particles in peripheral blood. The EM
      Bokashi(r) preparation used in the study was found to increase phagocytic
      activity mainly in monocytes, with an increased percentage of phagocytic cells in
      the experimental group. The highest serum lysozyme concentration in the piglets
      in the experimental group (2.89 mg/dl), was noted on day 42 of the study. In the
      group of pigs receiving EM Bokashi(r), the percentage of phagocytic cells with
      SWC3 (monocyte/granulocyte) expression was statistically significantly higher
      than in the control. The increase in the number of cells with SWC3
      (monocyte/granulocyte) expression in the peripheral circulation in combination
      with the greater capacity of the cells for phagocytosis and respiratory burst
      confirms that the non-specific immune response was modulated in the pigs
      supplemented with EM Bokashi(r).

PMID- 30187430
TI  - The impacts of local networks on subsistence resilience and biodiversity in a low
      lying Moluccan reef system between 1600 and the present.
AB  - Using field data for the 1980s and historic material, I show how the central
      places of networks crucial for regional and long-distance trades in the Moluccas
      between 1600 and the present were often environmentally vulnerable volcanic
      islands and low-lying reefs. After reviewing existing data on hazards, and
      evaluating the evidence for erosion and degradation, I suggest how resilience has
      been historically achieved through social and material exchanges between islands,
      accommodating the consequences of specific perturbations. Re-interpretation of
      published data shows how inter-island trade has re-organised patterns of
      biological interaction spatially and over the long term, helping us assess
      whether, in the face of climate-change effects, such areas are zones of
      robustness or of potential fragility.

PMID- 30187424
TI  - More than an Anti-diabetic Bariatric Surgery, Metabolic Surgery Alleviates
      Systemic and Local Inflammation in Obesity.
AB  - Obesity, associated with increased risk of type 2 diabetes (T2D), cardiovascular
      disease, and hepatic steatosis et al., has become a major global health problem.
      Recently, obesity has been proven to be under a status of low-grade, chronic
      inflammation, which contributes to insulin resistance and T2D. Bariatric surgery
      is currently an effective treatment for the control of morbid obesity and T2D,
      which impels ongoing efforts to clarify physiological and molecular mechanisms
      mediating these benefits. The correlation between obesity, inflammation, and T2D
      has been revealed to a certain extent, and studies have shed light on the effect
      of bariatric surgery on inflammatory status of subjects with obesity. Based on
      recent findings, this review focuses on the relationship between inflammation,
      obesity, and bariatric surgery.

PMID- 30187431
TI  - Coloring Book: A new method for testing language comprehension.
AB  - We present a new method for investigating children's language comprehension and
      argue that it has the potential to mitigate known task-related biases and expose
      children's grammatical and lexical knowledge in a more natural and ecologically
      valid manner. The new method consists of filling in a digital coloring page,
      according to sentence stimuli (e.g., The green monkey is being scratched by the
      blue monkey; The rabbit is red.). Through the playful act of coloring in the
      page, children reveal their interpretations of grammatical constructions and
      lexical items. We argue that this method gives more accurate results than
      existing methods, in which children are asked to choose among several pictures
      representing a number of possible interpretations. We present two experimental
      studies: one with Dutch-speaking children, tested on four types of grammatical
      constructions, and a second study with children learning Dutch as a second
      language, tested on their vocabulary knowledge. In both studies, the new method
      was compared with one of the most widely used methods: the picture selection
      task. In the first study where children's performance is said to be
      underestimated, the new method reveals better performance whereas in the second
      study where children's performance is assumed to be overestimated, the new method
      reveals lower performance. The results suggest therefore that the new task indeed
      decreases external task-related effects and offers a more reliable measurement of
      children's linguistic knowledge.

PMID- 30187432
TI  - A virtual reality approach identifies flexible inhibition of motion aftereffects
      induced by head rotation.
AB  - As we move in space, our retinae receive motion signals from two causes: those
      resulting from motion in the world and those resulting from self-motion. Mounting
      evidence has shown that vestibular self-motion signals interact with visual
      motion processing profoundly. However, most contemporary methods arguably lack
      portability and generality and are incapable of providing measurements during
      locomotion. Here we developed a virtual reality approach, combining a three-space
      sensor with a head-mounted display, to quantitatively manipulate the causality
      between retinal motion and head rotations in the yaw plane. Using this system, we
      explored how self-motion affected visual motion perception, particularly the
      motion aftereffect (MAE). Subjects watched gratings presented on a head-mounted
      display. The gratings drifted at the same velocity as head rotations, with the
      drifting direction being identical, opposite, or perpendicular to the direction
      of head rotations. We found that MAE lasted a significantly shorter time when
      subjects' heads rotated than when their heads were kept still. This effect was
      present regardless of the drifting direction of the gratings, and was also
      observed during passive head rotations. These findings suggest that the
      adaptation to retinal motion is suppressed by head rotations. Because the
      suppression was also found during passive head movements, it should result from
      visual-vestibular interaction rather than from efference copy signals. Such
      visual-vestibular interaction is more flexible than has previously been thought,
      since the suppression could be observed even when the retinal motion direction
      was perpendicular to head rotations. Our work suggests that a virtual reality
      approach can be applied to various studies of multisensory integration and
      interaction.

PMID- 30187433
TI  - Mymou: A low-cost, wireless touchscreen system for automated training of nonhuman
      primates.
AB  - Training nonhuman primates (NHPs) to perform cognitive tasks is essential for
      many neuroscientific investigations, yet laboratory training is a time-consuming
      process with inherent limitations. Habituating NHPs to the laboratory staff and
      experimental equipment can take months before NHPs are ready to proceed to the
      primary tasks. Laboratory training also necessarily separates NHPs from their
      home-room social group and typically involves some form of restraint or limited
      mobility, and data collection is often limited to a few hours per day so that
      multiple NHPs can be trained on the same equipment. Consequently, it can often
      take a year to train NHPs on complex cognitive tasks. To overcome these issues,
      we developed a low-cost, open-source, wireless touchscreen training system that
      can be installed in the home-room environment. The automated device can run
      continuously all day, including over weekends, without experimenter intervention.
      The system utilizes real-time facial recognition to initiate subject-specific
      tasks and provide accurate data logging, without the need for implanted
      microchips or separation of the NHPs. The system allows NHPs to select their
      preferred reward on each trial and to work when and for as long as they desire,
      and it can analyze task performance in real time and adapt the task parameters in
      order to expedite training. We demonstrate that NHPs consistently use this system
      on a daily basis to quickly learn complex behavioral tasks. The system therefore
      addresses many of the welfare and experimental limitations of laboratory-based
      training of NHPs and provides a platform for wireless electrophysiological
      investigations in more naturalistic, freely moving environments.

PMID- 30187434
TI  - Fast and slow errors: Logistic regression to identify patterns in accuracy
      response time relationships.
AB  - Understanding error and response time patterns is essential for making inferences
      in several domains of cognitive psychology. Crucial insights on cognitive
      performance and typical behavioral patterns are disclosed by using distributional
      analyses such as conditional accuracy functions (CAFs) instead of mean
      statistics. Several common behavioral error patterns revealed by CAFs are
      frequently described in the literature: response capture (associated with
      relatively fast errors), time pressure or urgency paradigms (slow errors), or cue
      induced speed-accuracy trade-off (evenly distributed errors). Unfortunately, the
      standard way of computing CAFs is problematic, because accuracy is averaged in RT
      bins. Here we present a novel way of analyzing accuracy-RT relationships on the
      basis of nonlinear logistic regression, to handle these problematic aspects of RT
      binning. First we evaluate the parametric robustness of the logistic regression
      CAF through parameter recovery. Second, we apply the function to three existing
      data sets showing that specific parametric changes in the logistic regression CAF
      can consistently describe common behavioral patterns (such as response capture,
      time pressure, and speed-accuracy trade-off). Finally, we discuss potential
      modifications for future research.

PMID- 30187436
TI  - A tutorial on DynaSearch: A Web-based system for collecting process-tracing data
      in dynamic decision tasks.
AB  - This tutorial describes DynaSearch, a Web-based system that supports process
      tracing experiments on coupled-system dynamic decision-making tasks. A major need
      in these tasks is to examine the process by which decision makers search over a
      succession of situation reports for the information they need in order to make
      response decisions. DynaSearch provides researchers with the ability to construct
      and administer Web-based experiments containing both between- and within-subjects
      factors. Information search pages record participants' acquisition of verbal,
      numeric, and graphic information. Questionnaire pages query participants' recall
      of information, inferences from that information, and decisions about appropriate
      response actions. Experimenters can access this information in an online viewer
      to verify satisfactory task completion and can download the data in comma
      separated text files that can be imported into statistical analysis packages.

PMID- 30187435
TI  - PLAViMoP: How to standardize and simplify the use of point-light displays.
AB  - The study of biological point-light displays (PLDs) has fascinated researchers
      for more than 40 years. However, the mechanisms underlying PLD perception remain
      unclear, partly due to difficulties with precisely controlling and transforming
      PLD sequences. Furthermore, little agreement exists regarding how transformations
      are performed. This article introduces a new free-access program called PLAViMoP
      (Point-Light Display Visualization and Modification Platform) and presents the
      algorithms for PLD transformations actually included in the software. PLAViMoP
      fulfills two objectives. First, it standardizes and makes clear many classical
      spatial and kinematic transformations described in the PLD literature.
      Furthermore, given its optimized interface, PLAViMOP makes these transformations
      easy and fast to achieve. Overall, PLAViMoP could directly help scientists avoid
      technical difficulties and make possible the use of PLDs for nonacademic
      applications.

PMID- 30187437
TI  - SMARTA: Automated testing apparatus for visual discrimination tasks.
AB  - This article introduces the open-source Subject-Mediated Automatic Remote Testing
      Apparatus (SMARTA) for visual discrimination tasks, which aims to streamline and
      ease data collection, eliminate or reduce observer error, increase interobserver
      agreement, and automate data entry without the need for an internet connection.
      SMARTA is inexpensive and easy to build, and it can be modified to accommodate a
      variety of experimental designs. Here we describe the utility and functionality
      of SMARTA in a captive setting. We present the results from a case study of color
      vision in ruffed lemurs (Varecia spp.) at the Duke Lemur Center in Durham, North
      Carolina, in which we demonstrate SMARTA's utility for two-choice color
      discrimination tasks, as well as its ability to streamline and standardize data
      collection. We also include detailed instructions for constructing and
      implementing the fully integrated SMARTA touchscreen system.

PMID- 30187438
TI  - Diagnosis and treatment of acute alcohol intoxication and alcohol withdrawal
      syndrome: position paper of the Italian Society on Alcohol.
AB  - The chronic use of alcohol can lead to the onset of an alcohol use disorder
      (AUD). About 50% of subjects with an AUD may develop alcohol withdrawal syndrome
      (AWS) when they reduce or discontinue their alcohol consumption and, in 3-5% of
      them, convulsions and delirium tremens (DTs), representing life-threatening
      complications, may occur. Unfortunately, few physicians are adequately trained in
      identifying and treating AWS. The Italian Society on Alcohol has, therefore,
      implemented a task force of specialists to draw up recommendations for the
      treatment of AWS with the following main results: (1) while mild AWS may not
      require treatment, moderate and severe AWS need to be pharmacologically treated;
      (2) out-patient treatment is appropriate in patients with mild or moderate AWS,
      while patients with severe AWS need to be treated as in-patients; (3)
      benzodiazepines, BDZs are the "gold standard" for the treatment of AWS and DTs;
      (4) alpha-2-agonists, beta-blockers, and neuroleptics may be used in association
      when BDZs do not completely resolve specific persisting symptoms of AWS; (5) in
      the case of a refractory form of DTs, the use of anaesthetic drugs (propofol and
      phenobarbital) in an intensive care unit is appropriate; (6) alternatively to
      BDZs, sodium oxybate, clomethiazole, and tiapride approved in some European
      Countries for the treatment of AWS may be employed for the treatment of moderate
      AWS; (7) anti-convulsants are not sufficient to suppress AWS, and they may be
      used only in association with BDZs for the treatment of refractory forms of
      convulsions in the course of AWS.

PMID- 30187440
TI  - The Influence of a Home-Based Education Intervention on Family Caregivers'
      Knowledge and Self-Efficacy for Cancer Pain Management in Adult Patients Within a
      Resource-Limited Setting.
AB  - Cancer-related pain is prevalent and has debilitating effects on patients and
      their family. The effects of cancer pain can be curtailed if the family members
      caring for the patient receive essential support to enhance their capabilities
      for cancer pain management. Little has been done to study the available support
      to family caregivers (FCGs) towards pain management in adult cancer patients
      (ACPs) living in resource-limited countries where the burden of cancer is on the
      rise. This study evaluated the influence of an education intervention delivered
      in the home setting on FCGs' knowledge and self-efficacy (SE) for pain management
      in ACPs. One-group pre-/post-test design was used in a sample of 54 FCGs who had
      been caring for ACPs suffering from pain for at least 1 month. Data were
      collected using the Family Pain Questionnaire and Caregiver Pain Management SE
      Scale. The FCGs' mean knowledge score post-intervention (26.69 +/- 10) was higher
      than the baseline (45 +/- 12.9), and the difference was statistically significant
      (t = 10.382, p = 0.000, CI = 17.12-25.43). Additionally, the FCGs' mean SE score
      post-intervention (1003.30 +/- 191) was higher than the baseline (648.3 +/-
      273.4), and the difference was statistically significant (t = - 8.52, p = 0.000,
      CI = - 438.6-- 271.4). The home-based education intervention significantly and
      positively influenced the FCGs' knowledge and SE for pain management while at
      home. Cancer pain management educational interventions delivered at home should
      be considered as one of the strategies for enhancing cancer care in resource
      limited settings.

PMID- 30187441
TI  - The influence of size in weight illusions is unique relative to other object
      features.
AB  - Research into weight illusions has provided valuable insight into the functioning
      of the human perceptual system. Associations between the weight of an object and
      its other features, such as its size, material, density, conceptual information,
      or identity, influence our expectations and perceptions of weight. Earlier
      accounts of weight illusions underscored the importance of previous interactions
      with objects in the formation of these associations. In this review, we propose a
      theory that the influence of size on weight perception could be driven by innate
      and phylogenetically older mechanisms, and that it is therefore more deep-seated
      than the effects of other features that influence our perception of an object's
      weight. To do so, we first consider the different associations that exist between
      the weight of an object and its other features and discuss how different object
      features influence weight perception in different weight illusions. After this,
      we consider the cognitive, neurological, and developmental evidence, highlighting
      the uniqueness of size-weight associations and how they might be reinforced
      rather than driven by experience alone. In the process, we propose a novel
      neuroanatomical account of how size might influence weight perception differently
      than other object features do.

PMID- 30187439
TI  - The role of ADAMTS4 and ADAMTS9 in cardiovascular disease in premature ovarian
      insufficiency and idiopathic hypogonadotropic hypogonadism.
AB  - PURPOSE: We aimed to determine the relation of a disintegrin and
      metalloproteinase with thrombospondin motifs-4 (ADAMTS4), and a disintegrin and
      metalloproteinase with thrombospondin motifs-9 (ADAMTS9) with cardiovascular
      disease (CVD) risk, in ovarian dysfunction patients with premature ovarian
      insufficiency (POI), and idiopathic hypogonadotropic hypogonadism (IHH). METHODS:
      43 IHH and 44 POI patients were enrolled to this case-control study. Serum
      hormonal parameters, lipid profiles, ADAMTS4 and ADAMTS9 levels were measured.
      Lipid accumulation product (LAP) index, visceral adiposity index (VAI), and
      homeostasis model assessment of insulin resistance (HOMA-IR) were calculated. The
      patients with at least two out of the four following criteria were accepted to
      have increased CVD risk; waist-to-hip ratio (WHR) >= 0.8, waist circumference
      (WC) >= 79 cm, triglycerides (TG) >= 150 mg/dL, high-density lipoprotein
      cholesterol (HDL-C) < 50 mg/dL. Serum ADAMTS4 and ADAMTS9 levels were measured by
      enzyme-linked immunosorbent assay (ELISA). RESULTS: ADAMTS4 and ADAMTS9 levels
      were significantly higher in the IHH group than the POI group (p = 0.002, and p =
      0.013, respectively). IHH group had significantly higher levels of insulin, HOMA
      IR index, and LAP index (p = 0.006, p = 0.005, and p = 0.013, respectively). The
      mean age of patients in the IHH group (23.60 +/- 5.64 years) was significantly
      lower than the POI group (31.05 +/- 6.03 years), (p < 0.001). Odds ratios (OR)
      were 1.236 (95% CI 1.055-1.447) and 1.002 (95% CI 1.000-1.004) for LAP index and
      ADAMTS4, respectively, in the IHH group. These two parameters found to have high
      predictivity for CVD risk in the IHH group (p = 0.009 and p = 0.028,
      respectively). CONCLUSION: The lower levels of ADAMTS4 in the POI group, when
      compared with the IHH patients pointed out that even limited hormone secretion
      and ovulation in the POI group, may have protective effect on cardiovascular
      system. The higher levels of ADAMTS4 and LAP index in the IHH group demonstrated
      the increased risk of these patients for CVD.

PMID- 30187442
TI  - Disentangling cross-language orthographic neighborhood from markedness effects in
      L2 visual word recognition.
AB  - Previous research has reported that lexical access in bilinguals is language non
      selective. In the present study, we explored the extent to which cross-language
      orthographic neighborhood size (N-size) effects, an index of language non
      selectivity, should be dissociated from markedness effects, a sub-lexical
      orthographic variable referring to the degree of language- shared (unmarked)
      versus specific (marked) orthography. Two proficiency groups of French/English
      bilinguals performed an English (L2) lexical decision task with three word and
      non-word conditions: (1) English words with large French N-size/unmarked
      orthography (price), (2) small French N-size/unmarked orthography (drive), and
      (3) small French N-size/marked orthography (write). Evidence was found for
      orthographic markedness effects, albeit with a different pattern for word and non
      word processing: while marked words were facilitated (responded to faster and
      more accurately) compared to unmarked words, the opposite pattern emerged for non
      words. The pattern of results was comparable in both proficiency groups. No
      evidence emerged for the influence of first language (L1) neighborhood on L2 word
      or non-word processing. Thus, the results emphasize the need to integrate
      orthographic markedness as a relevant psycholinguistic variable in bilingual
      models of visual word recognition such as BIA/+ and to take it into account when
      investigating cross- language effects and the issue of language non-selectivity
      during visual word recognition.

PMID- 30187443
TI  - The Influence of Diabetes Mellitus on Glucuronidation and Sulphation of
      Paracetamol in Patients with Febrile Neutropenia.
AB  - BACKGROUND AND OBJECTIVES: Numerous studies have confirmed the influence of
      diabetes mellitus on the pharmacokinetics of drugs. Paracetamol (APAP) is an
      antipyretic that is commonly used in febrile neutropenia (FN) therapy. APAP is
      chiefly metabolised by glucuronidation and sulphation. This study assessed the
      influence of diabetes on the pharmacokinetics of paracetamol and its metabolites:
      glucuronide (APAP-glu) and sulfate (APAP-sulfate) in FN patients. METHODS:
      Patients with FN received single intravenous dose 1000 mg of APAP. The FN
      patients were allocated to one of two groups: diabetics (DG, n = 7) or non
      diabetics (NDG, n = 11). The plasma concentrations of paracetamol and its
      metabolites were measured with the validated high-performance liquid
      chromatography (HPLC) with ultraviolet (UV) detection. RESULTS: Pharmacokinetic
      parameters (mean [SD]) of APAP in the DG and NDG groups were as follows: Cmax
      (maximum comcentration) = 21.50 [11.23] vs. 23.42 [9.79] mg/L, AUC0-t (area under
      the concentration-time curve) = 44.23 [17.93] vs. 41.43 [14.57] mg.h/L, t1/2kel
      (elimination half-life) = 2.28 [0.80] vs. 2.11 [0.80] h. In both groups the
      exposure to APAP was comparable. The study did not reveal differences between the
      two groups in the pharmacokinetics of APAP-glu and APAP-sulfate. The Cmax and
      AUC0-t ratio between the metabolites and APAP were similar. CONCLUSIONS: No
      differences in the pharmacokinetics of APAP, APAP-glu and APAP-sulfate in
      patients with FN indicates that diabetes does not influence glucuronidation and
      sulfatation of paracetamol.

PMID- 30187444
TI  - Evaluating the Accelerated Blood Clearance Phenomenon of PEGylated Nanoemulsions
      in Rats by Intraperitoneal Administration.
AB  - The accelerated blood clearance (ABC) phenomenon is induced by repeated
      intravenous injection of stealth polyethylene glycol (PEG) nanocarriers and
      appears as the alteration of the pharmacokinetics and biodistribution of the
      second administration. Nevertheless, there is no any report about the ABC
      phenomenon induced by intraperitoneal administration of PEGylated nanocarriers.
      In this study, we firstly observed whether the ABC phenomenon is induced with
      PEGylated nanoemulsion at the dose of 0.5~100 MUmol phospholipid.kg-1 by
      intraperitoneal/intravenous injections in rats. The PEG (molecule weight, 2000)
      modified nanoemulsions PE-B and PE in which fluorescence indicator
      dialkylcarbocyanines (DiR) is encapsulated by PE-B were prepared for this work.
      The pharmacokinetics of the first injected PE via veins or peritoneal cavity
      features different variation trends. Moreover, the tissue distributions (in vivo
      or in vitro) of the first injected PE by intraperitoneal injection reveals that
      the PE gains access to the whole lymphatic circulatory system. Furthermore, our
      results demonstrate that the ABC phenomenon can be induced by intraperitoneal
      administration PE-B and present obvious changes with varying PE-B concentration
      0.5~100 MUmol phospholipid.kg-1. Moreover, an interesting point is that the ABC
      phenomenon induced by intraperitoneal injected PE-B can be significantly
      inhibited by intraperitoneal pre-injection of distilled water. For understanding
      this issue clear, we studied the production of anti-PEG IgM and the
      characteristic morphologies of immune cells. We observed that the mast cells in
      peritoneal cavity exhibit rapid depletion in response to the intraperitoneal pre
      injection of distilled water, while the anti-PEG IgM secretes at the same level.

PMID- 30187445
TI  - Third-Generation Transdermal Delivery Systems Containing Zidovudine: Effect of
      the Combination of Different Chemical Enhancers and a Microemulsion System.
AB  - This study aimed to examine the influence of the combination of chemical
      enhancers and a microemulsion on the transdermal permeation of zidovudine (AZT).
      Ethanol, 1,8-cineole, and geraniol were incorporated in a microemulsion. The
      droplet size, zeta potential, rheology, and SAXS analysis were performed. The
      permeation enhancer effect was evaluated using pig ear skin. Snake skin (Boa
      constrictor) treated with the formulations was also used as a stratum corneum
      model and studied by attenuated total reflectance-infrared spectroscopy. As a
      result, it was observed that the incorporation of the chemical enhancers promoted
      a decrease of the droplet size and some rheological modifications. The 1,8
      cineole associated with the microemulsion significantly increased the permeated
      amount of AZT. Conversely, ethanol significantly increased the quantity of the
      drug retained in the skin. The probable mechanism for the cineole and ethanol
      effects was respectively: fluidization and increasing of the diffusion
      coefficient, and increasing of the partition coefficient. Surprising, geraniol +
      microemulsion drastically decreased both the permeated and the retained amount of
      AZT into the skin. Thus, the adequate association of microemulsion and chemical
      enhancers showed to be a crucial step to enable the topical or transdermal use of
      drugs.

PMID- 30187446
TI  - Colloidally Stable Small Unilamellar Stearyl Amine Lipoplexes for Effective BMP-9
      Gene Delivery to Stem Cells for Osteogenic Differentiation.
AB  - The biocompatibility of cationic liposomes has led to their clinical translation
      in gene delivery and their application apart from cancer to cardiovascular
      diseases, osteoporosis, metabolic diseases, and more. We have prepared PEGylated
      stearyl amine (pegSA) lipoplexes meticulously considering the physicochemical
      properties and formulation parameters to prepare single unilamellar vesicles
      (SUV) of < 100 nm size which retain their SUV nature upon complexation with pDNA
      rather than the conventional lipoplexes which show multilamellar nature. The
      developed PEGylated SA lipoplexes (pegSA lipoplexes) showed a lower N/P ratio
      (1.5) for BMP-9 gene complexation while maintaining the SUV character with a
      unique shape (square and triangular lipoplexes). Colloidal and pDNA complexation
      stability in the presence of electrolytes and serum indicates the suitability for
      intravenous administration for delivery of lipoplexes to bone marrow mesenchymal
      stem cells through sinusoidal vessels in bone marrow. Moreover, lower charge
      density of lipoplexes and low oxidative stress led to lower toxicity of
      lipoplexes to the C2C12 cells, NIH 3T3 cells, and erythrocytes. Transfection
      studies showed efficient gene delivery to C2C12 cells inducing osteogenic
      differentiation through BMP-9 expression as shown by enhanced calcium deposition
      in vitro, proving the potential of lipoplexes for bone regeneration. In vivo
      acute toxicity studies further demonstrated safety of the developed lipoplexes.
      Developed pegSA lipoplexes show potential for further in vivo preclinical
      evaluation to establish the proof of concept.

PMID- 30187447
TI  - Preparation of a Mesoporous Structure of SnO2 for Increasing the Oral
      Bioavailability and Dissolution Rate of Nitrendipine.
AB  - In this study, mesoporous SnO2 (MSn) with a three-dimensional mesoporous
      structure was prepared using MCM-48 as the template in order to increase the oral
      bioavailability and dissolution rate of insoluble drugs. The model drug,
      nitrendipine (NDP), was loaded into the MSn by the adsorption method. The
      structural features of MSn were characterized by transmission electron microscopy
      (TEM), scanning electron microscopy (SEM), and N2 adsorption (desorption)
      analysis. NDP was existed in the pore channels of MSn in an amorphous state,
      which was characterized by powder X-ray diffraction (PXRD), differential scanning
      calorimetry (DSC), and Fourier transform infrared spectroscopy (FTIR). MSn showed
      a good biocompatibility in the cell toxicity assay for Caco-2 cells. In vitro
      dissolution results suggested that MSn could significantly enhance the
      dissolution rate of NDP compared with commercial NDP tablets. Pharmacokinetic
      studies indicated that NDP-MSn tablets effectively enhanced the oral
      bioavailability of NDP. In conclusion, MSn was found to be a potential carrier
      for improving the solubility of insoluble drugs.

PMID- 30187448
TI  - Correction to: Analysis of Cotranslational Polyamine Sensing During Decoding of
      ODC Antizyme mRNA.
AB  - Correction to: Chapter 26 in: Ruben Alcazar and Antonio F. Tiburcio (eds.),
      Polyamines: Methods and Protocols, Methods in Molecular Biology, vol. 1694,
      https://doi.org/10.1007/978-1-4939-7398-9_26.

PMID- 30187449
TI  - Eighth American Joint Committee on Cancer (AJCC) melanoma classification: what
      about stage IIC?

PMID- 30187450
TI  - Dornase alfa for cystic fibrosis.
AB  - BACKGROUND: Dornase alfa is currently used as a mucolytic to treat pulmonary
      disease (the major cause of morbidity and mortality) in cystic fibrosis. It
      reduces mucus viscosity in the lungs, promoting improved clearance of secretions.
      This is an update of a previously published review. OBJECTIVES: To determine
      whether the use of dornase alfa in cystic fibrosis is associated with improved
      mortality and morbidity compared to placebo or other medications that improve
      airway clearance, and to identify any adverse events associated with its use.
      SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders
      Group Trials Register which comprises references identified from comprehensive
      electronic database searches, handsearching relevant journals and abstracts from
      conferences. Date of the most recent search of the Group's Cystic Fibrosis
      Register: 23 April 2018.Clinicaltrials.gov and the International Clinical Trials
      Registry Platform were also searched to identify unpublished or ongoing trials.
      Date of most recent search: 07 June 2018. SELECTION CRITERIA: All randomised and
      quasi-randomised controlled trials comparing dornase alfa to placebo, standard
      therapy or other medications that improve airway clearance. DATA COLLECTION AND
      ANALYSIS: Authors independently assessed trials against the inclusion criteria;
      two authors carried out analysis of methodological quality and data extraction.
      GRADE was used to assess the level of evidence. MAIN RESULTS: The searches
      identified 69 trials, of which 19 (2565 participants) met our inclusion criteria.
      Fifteen trials compared dornase alfa to placebo or no dornase alfa (2447
      participants); two compared daily dornase to hypertonic saline (32 participants);
      one compared daily dornase alfa to hypertonic saline and alternate day dornase
      alfa (48 participants); one compared dornase alfa to mannitol and the combination
      of both drugs (38 participants). Trial duration varied from six days to three
      years.Dornase alfa compared to placebo or no treatmentDornase alfa improved
      forced expiratory volume at one second at one month (four trials, 248
      participants), three months (one trial, 320 participants; moderate-quality
      evidence), six months (one trial, 647 participants; high-quality evidence) and
      two years (one trial, 410 participants). Limited low-quality evidence showed no
      difference between groups for changes in quality of life. There was a decrease in
      pulmonary exacerbations with dornase alfa in trials of up to two years (moderate
      quality evidence). One trial that examined the cost of care, including the cost
      of dornase alfa, found that the cost savings from dornase alfa offset 18% to 38%
      of the medication costs.Dornase alfa: daily versus alternate dayOne cross-over
      trial (43 children) found no differences between treatment regimens for lung
      function, quality of life or pulmonary exacerbations (low-quality
      evidence).Dornase alfa compared to other medications that improve airway
      clearanceResults for these comparisons were mixed. One trial (43 children) showed
      a greater improvement in forced expiratory volume at one second for dornase alfa
      compared to hypertonic saline (low-quality evidence), and one trial (23
      participants) reported no difference in lung function between dornase alfa and
      mannitol or dornase alfa and dornase alfa plus mannitol (low-quality evidence).
      One trial (23 participants) found a difference in quality of life favouring
      dornase alfa when compared to dornase alfa plus mannitol (low-quality evidence);
      other comparisons found no difference in this outcome (low-quality evidence). No
      trials in any comparison reported any difference between groups in the number of
      pulmonary exacerbations (low-quality evidence).When all comparisons are assessed,
      dornase alfa did not cause significantly more adverse effects than other
      treatments, except voice alteration and rash. AUTHORS' CONCLUSIONS: There is
      evidence to show that, compared with placebo, therapy with dornase alfa improves
      lung function in people with cystic fibrosis in trials lasting from one month to
      two years. There was a decrease in pulmonary exacerbations in trials of six
      months or longer. Voice alteration and rash appear to be the only adverse events
      reported with increased frequency in randomised controlled trials. There is not
      enough evidence to firmly conclude if dornase alfa is superior to other
      hyperosmolar agents in improving lung function.

PMID- 30187452
TI  - Temperature and humidity affect the incidence of hand, foot, and mouth disease: a
      systematic review of the literature - a report from the International Society of
      Dermatology Climate Change Committee.
AB  - Hand, foot, and mouth disease (HFMD) is an enterovirus-mediated condition that
      predominantly affects children under 5 years of age. The tendency for outbreaks
      to peak in warmer summer months suggests a relationship between HFMD and weather
      patterns. We reviewed the English-language literature for articles describing a
      relationship between meteorological variables and HFMD. Seventy-two studies
      meeting criteria were identified. A positive, statistically significant
      relationship was identified between HFMD cases and both temperature (61 of 67
      studies, or 91.0%, reported a positive relationship) [CI 81.8-95.8%, P = 0.0001]
      and relative humidity (41 of 54 studies, or 75.9%) [CI 63.1-85.4%, P = 0.0001].
      No significant relationship was identified between HFMD and precipitation, wind
      speed, and/or sunshine. Most countries reported a single peak of disease each
      year (most commonly early Summer), but subtropical and tropical climate zones
      were significantly more likely to experience a bimodal distribution of cases
      throughout the year (two peaks a year; most commonly late spring/early summer,
      with a smaller peak in autumn). The rising global incidence of HFMD, particularly
      in Pacific Asia, may be related to climate change. Weather forecasting might be
      used effectively in the future to indicate the risk of HFMD outbreaks and the
      need for targeted public health interventions.

PMID- 30187451
TI  - Comparing apples and oranges: Why infant bone collagen may not reflect dietary
      intake in the same way as dentine collagen.
AB  - OBJECTIVES: Recent developments in incremental dentine analysis allowing
      increased temporal resolution for tissues formed during the first 1,000 days of
      life have cast doubt on the veracity of weaning studies using bone collagen
      carbon (delta13 C) and nitrogen (delta15 N) isotope ratio data from infants.
      Here, we compare published bone data from the well-preserved Anglo-Saxon site of
      Raunds Furnells, England, with co-forming dentine from the same individuals, and
      investigate the relationship of these with juvenile stature. The high-resolution
      isotope data recorded in dentine allow us to investigate the relationship of diet
      with juvenile stature during this critical period of life. MATERIALS AND METHODS:
      We compare incremental dentine collagen delta13 C and delta15 N data to published
      bone collagen data for 18 juveniles and 5 female adults from Anglo Saxon Raunds
      Furnells alongside new data for juvenile skeletal and dental age. An improvement
      in the method by sampling the first 0.5 mm of the sub-cuspal or sub-incisal
      dentine allows the isotopic measurement of dentine formed in utero. RESULTS AND
      DISCUSSION: delta13 C profiles for both dentine and bone are similar and more
      robust than delta15 N for estimating the age at which weaning foods are
      introduced. Our results suggest delta15 N values from dentine can be used to
      evaluate the maternal/in utero diet and physiology during pregnancy, and that
      infant dentine profiles may reflect diet PLUS an element of physiological stress.
      In particular, bone collagen fails to record the same range of delta15 N as co
      forming dentine, especially where growth is stunted, suggesting that infant bone
      collagen is unreliable for weaning studies.

PMID- 30187453
TI  - Can I take my normal painkillers doctor? Therapeutic management of pain following
      dermatological procedures.
AB  - Dermatological procedures performed purely under local anaesthesia can provide
      excellent intraoperative analgesia. However, post-procedure patients can have
      significant pain. Consequences of pain include patient distress, poor compliance
      with dressings and subsequent delayed wound healing as well as the potential fear
      and avoidance of further procedures. Anecdotally the same postoperative analgesia
      regime is given to all dermatology patients. There is a general fear by
      dermatologists of nonsteroidal anti-inflammatory drugs (NSAIDs) due to perceived
      risk of postoperative bleeding and of tramadol due to its sedative effects.
      Understanding of pharmacology within the patient population and their
      comorbidities is necessary in choosing the appropriate analgesic regime. We
      reviewed the most commonly used analgesics, giving a summary of the important
      pharmacology and evidence of their use in the literature in order to allow
      clinicians to give individual approach to managing post-procedure analgesia.

PMID- 30187454
TI  - Misinterpretation of blood group and antibody screen leading to serious errors in
      RhD immunoglobulin administration: A report on first two years of data from
      Serious Transfusion Incident Reporting program.
AB  - The Serious Transfusion Incident Reporting program (STIR) commenced
      haemovigilance in relation to RhD immunoglobulin (Ig) administration in 2015.
      During two years of reporting, 21 reports relating to RhD Ig administration were
      received. Thirty-three percent (7/21) were related to omission of RhD Ig, putting
      women at risk of RhD alloimmunisation and adverse consequences in future
      pregnancies. A recent case reported to STIR highlights poor communication and
      misinterpretation of pathology results leading to significant morbidity from
      haemolysis in the fetus. STIR makes recommendations related to education of staff
      and communication between clinical and laboratory staff to improve the safety of
      patient care.

PMID- 30187455
TI  - Economic disadvantage and math achievement: The significance of perceived cost
      from an evolutionary perspective.
AB  - BACKGROUND: Children growing up in poverty tend to perform worse in school than
      their more economically advantaged peers. AIMS: The current study integrates an
      educational theory of motivation and an evolutionary theory of life history
      strategies to examine how economic disadvantage predicts children's mathematics
      achievement through their academic beliefs and values. SAMPLE: Participants were
      1,536 students (Mage  = 12.88) in a large metropolitan city in the United States.
      METHODS: Economic disadvantage was assessed via school reports of the student
      being eligible to receive free or reduced-price lunch during the 2014-2015 school
      year (i.e., at or below 185% of the federal poverty line). Students reported on
      their perceived interest, usefulness, and cost of learning mathematics during the
      first half of the 2015-2016 school year (August to December). Mathematics
      achievement for both school years was assessed via school reports of mathematics
      grades. RESULTS: Children receiving free or reduced-price lunch showed higher
      perceived cost of learning mathematics, and this in turn predicted changes in
      mathematics achievement over time, indirect effect = -0.57, 95% CI (-0.97, 
      0.23). However, neither interest nor perceived usefulness or ability in
      mathematics mediated the association between economic disadvantage and changes in
      mathematics achievement. CONCLUSIONS: Results underscore the potential for
      interventions to target students' perceived cost of learning as a way to increase
      school engagement, particularly among disadvantaged students.

PMID- 30187456
TI  - An unusual case of melanocytic matricoma in a young pregnant woman.

PMID- 30187457
TI  - Cutaneous mucormycosis caused by Mucor irregularis in a patient with CARD9
      deficiency.

PMID- 30187458
TI  - Digest: Ecological crossover effects on sexual selection.
AB  - Environmental conditions during birds' nonbreeding season can affect the
      manifestation of secondary sexual traits and therefore sexual selection. In pied
      flycatchers, the size of the wing patch is a secondary sexual trait that signals
      mate value and is influenced by the previous winter's conditions. Female
      preference changes accordingly with the conditions of the previous nonbreeding
      season.

PMID- 30187460
TI  - Dermoscopic features of subungual exostosis.

PMID- 30187461
TI  - Etanercept biosimilar SB4 in the treatment of chronic plaque psoriasis: data from
      the Psobiosimilars registry.

PMID- 30187459
TI  - Therapeutic effects of bee venom and its major component, melittin, on atopic
      dermatitis in vivo and in vitro.
AB  - BACKGROUND AND PURPOSE: Atopic dermatitis (AD) is a multifactorial skin condition
      with complex interactions of innate and adaptive immune responses. There are
      several existing therapies for AD, including topical glucocorticosteroids,
      emollients, phototherapies, calcineurin inhibitors and immunosuppressants, such
      as cyclosporine A. Although these therapies reduce inflammation, they also cause
      serious side effects. Therefore, it is necessary to develop new therapeutic
      approaches for AD treatment without side effects. There are several studies on
      natural materials or toxins, such as herbs, ginseng extract and snake venom, for
      AD treatment. However, treatment of AD with bee venom and its major component,
      melittin has rarely been studied. EXPERIMENTAL APPROACH: Effects of bee venom and
      melittin were studied in a model of AD in vivo induced by 1-chloro-2,4
      dinitrobenzene (DNCB) in female Balb/c mice and in cultures of human
      keratinocytes, stimulated by TNF-alpha/IFN-gamma. The potential pharmacological
      effects of bee venom and melittin on these in vivo and in vitro AD-like skin
      disease models were studied. KEY RESULTS: Bee venom and melittin exhibited potent
      anti-atopic activities, shown by decreased AD-like skin lesions, induced by DNCB
      in mice. In vitro studies using TNF-alpha/IFN-gamma-stimulated human
      keratinocytes showed that bee venom and melittin inhibited the increased
      expression of chemokines, such as CCL17 and CCL22, and pro-inflammatory
      cytokines, including IL-1beta, IL-6 and IFN-gamma, through the blockade of the NF
      kappaB and STAT signalling pathways. CONCLUSIONS AND IMPLICATIONS: Our results
      suggest that bee venom and melittin would be suitable for epicutaneous
      application, as topical administration is often appropriate for the treatment of
      AD.

PMID- 30187462
TI  - Stepwise evolution of floral pigmentation predicted by biochemical pathway
      structure.
AB  - Developmental pathways play a major role in influencing the distribution of
      naturally occurring phenotypes. For example, pathway structure and regulation
      could make some phenotypes inaccessible or restrict the routes through which
      phenotypes evolve. In this study, we examine floral anthocyanin pigments across
      the Solanaceae family and test whether patterns of phenotypic variation are
      consistent with predicted constraints based on the structure of the flavonoid
      biosynthetic pathway. We find that anthocyanin evolution occurs in a stepwise
      manner whereby transitions between the production of red mono hydroxylated
      pelargonidin pigments and blue trihydroxylated delphinidin pigments first passes
      through an intermediate step of producing purple dihydroxylated cyanidin
      pigments. Although the transitions between these three pigment types differ in
      frequency, we infer that these shifts are often reversible, suggesting that the
      functionality of the underlying biochemical pathway is generally conserved.
      Furthermore, our study finds that some pigment combinations are never observed,
      pointing to additional constraints on naturally occurring phenotypes. Overall,
      our findings provide insights into how the structure of an angiosperm-wide
      biochemical pathway has shaped macroevolutionary variation in floral
      pigmentation.

PMID- 30187463
TI  - The female ancestor's tale: Long-term matrilineal continuity in a nonisolated
      region of Tuscany.
AB  - OBJECTIVES: With the advent of ancient DNA analyses, it has been possible to
      disentangle the contribution of ancient populations to the genetic pool of the
      modern inhabitants of many regions. Reconstructing the maternal ancestry has
      often highlighted genetic continuity over several millennia, but almost always in
      isolated areas. Here we analyze North-western Tuscany, a region that was a
      corridor of exchanges between Central Italy and the Western Mediterranean coast.
      MATERIALS AND METHODS: We newly obtained mitochondrial HVRI sequences from 28
      individuals, and after gathering published data, we collected genetic information
      for 119 individuals from the region. Those span five periods during the last
      5,000 years: Prehistory, Etruscan age, Roman age, Renaissance, and Present-day.
      We used serial coalescent simulations in an approximate Bayesian computation
      framework to test for continuity between the mentioned groups. RESULTS: Our
      analyses always favor continuity over discontinuity for all groups considered,
      with the Etruscans being part of the genealogy. Moreover, the posterior
      distributions of the parameters support very small female effective population
      sizes. CONCLUSIONS: The observed signals of long-term genetic continuity and
      isolation are in contrast with the history of the region, conquered several times
      (Etruscans, Romans, Lombards, and French). While the Etruscans appear as a local
      population, intermediate between the prehistoric and the other samples, we
      suggest that the other conquerors-arriving from far-had a consistent social or
      sex bias, hence only marginally affecting the maternal lineages. At the same
      time, our results show that long-term genealogical continuity is not necessarily
      linked to geographical isolation.

PMID- 30187464
TI  - OpenMICE: an open spatial and temporal data set of small mammals in south-central
      Italy based on owl pellet data.
AB  - The use of database technologies as a tool for implementing data for quantitative
      ecological studies and biodiversity conservation planning has recently attracted
      the attention of the biological community. Despite the fact that the number of
      biodiversity data sets is quickly rising, online databases of small mammals are
      still scarce, especially for Mediterranean ecosystems. We implemented the first
      standardized and accessible georeferenced European database of small mammal
      occurrences, abundances, and functional traits. Data derived from owl pellets was
      obtained from different sources, including original field surveys, publications,
      gray literature, existing databases, and museum collections. The OpenMICE
      database covers the years 1972 to 2017 and includes nearly 50,000 individuals
      from 23 species (13 Rodentia and 10 Eulipotyphla) at 190 sites in south-central
      Italy. Our specific goals in compiling this data set were as follows: (1) to make
      data that is usually accessible to a restricted audience widely available; (2) to
      identify the gaps in knowledge about small mammal communities and guide future
      sampling and conservation efforts; and (3) to gain a first insight into small
      mammal diversity and abundance in the study area. The potential applications of
      our spatial relational database are many, from individual-based to community
      based models as potential indicators of environmental changes at different
      geographical scales. Given the long-term support for data storage, the OpenMICE
      database could be further expanded to include other geographical contexts and
      implemented with new information and traits. We would appreciate that researchers
      cite this paper if using all or part of the data set. We also request that
      researchers and teachers inform us of how they are using the data. We intend to
      keep it up to date as novel studies become available (see Data Availability).

PMID- 30187465
TI  - The onset of hand stereotypies in fragile X syndrome.

PMID- 30187466
TI  - More studies are needed in paediatric neurodisability.

PMID- 30187467
TI  - Transformative journeys in childhood-onset disability with the AACPDM.

PMID- 30187468
TI  - Standardized and individualized care: do they complement or oppose each other?

PMID- 30187469
TI  - Low temperature decreases bone mass in mice: Implications for humans.
AB  - OBJECTIVES: Humans exhibit significant ecogeographic variation in bone size and
      shape. However, it is unclear how significantly environmental temperature
      influences cortical and trabecular bone, making it difficult to recognize
      adaptation versus acclimatization in past populations. There is some evidence
      that cold-induced bone loss results from sympathetic nervous system activation
      and can be reduced by nonshivering thermogenesis (NST) via uncoupling protein
      (UCP1) in brown adipose tissue (BAT). Here we test two hypotheses: (1) low
      temperature induces impaired cortical and trabecular bone acquisition and (2)
      UCP1, a marker of NST in BAT, increases in proportion to degree of low
      temperature exposure. METHODS: We housed wildtype C57BL/6J male mice in pairs at
      26  degrees C (thermoneutrality), 22  degrees C (standard), and 20  degrees C
      (cool) from 3 weeks to 6 or 12 weeks of age with access to food and water ad
      libitum (N = 8/group). RESULTS: Cool housed mice ate more but had lower body fat
      at 20  degrees C versus 26  degrees C. Mice at 20  degrees C had markedly lower
      distal femur trabecular bone volume fraction, thickness, and connectivity density
      and lower midshaft femur cortical bone area fraction versus mice at 26  degrees C
      (p < .05 for all). UCP1 expression in BAT was inversely related to temperature.
      DISCUSSION: These results support the hypothesis that low temperature was
      detrimental to bone mass acquisition. Nonshivering thermogenesis in brown adipose
      tissue increased in proportion to low-temperature exposure but was insufficient
      to prevent bone loss. These data show that chronic exposure to low temperature
      impairs bone architecture, suggesting climate may contribute to phenotypic
      variation in humans and other hominins.

PMID- 30187470
TI  - The role of neighbourhood greenspace in children's spatial working memory.
AB  - BACKGROUND: Exposure to nature may be particularly beneficial for the brain
      regions that support spatial working memory, a strong correlate of academic
      achievement. AIMS: To explore whether children living in greener neighbourhoods
      (wards) have better spatial working memory. SAMPLE: Drawn from the UK's
      Millennium Cohort Study, the sample was 4,758 11-year-olds living in urban areas
      in England. METHODS: We fitted two-level regression models, with children nested
      in wards, before and after adjustment for confounders, including poverty,
      parental education, sports participation, neighbourhood deprivation, and
      neighbourhood history. Spatial working memory was measured using the Cambridge
      Neuropsychological Test Automated Battery Spatial Working Memory task. Greenspace
      was measured as the percentage of greenery in the child's ward. RESULTS: Even
      after controlling for confounders, lower quantity of neighbourhood greenspace was
      related to poorer spatial working memory. Importantly, neighbourhood deprivation
      did not modify this relationship. Therefore, lower quantity of greenspace was
      related to poorer spatial working memory similarly in deprived and non-deprived
      neighbourhoods. CONCLUSIONS: Children living in greener urban neighbourhoods have
      better spatial working memory. If this association is causal, then our findings
      can be used to inform policy decisions about both education and urban planning.

PMID- 30187471
TI  - Antigens and Antibodies in Disease With Specifics About CGRP Immunology.
AB  - Growth in knowledge about calcitonin gene-related peptide (CGRP) in the
      pathophysiology of migraine brought CGRP antagonism to headache medicine.
      Failures in development of small molecule CGRP receptor antagonists and
      increasing knowledge and use of monoclonal antibodies (mAbs) in medicine led to
      the breakthrough development of large molecule anti-CGRP mAbs: eptinezumab,
      erenumab, fremanezumab, and galcanezumab. This specifics about CGRP immunology
      aims to outline: (1) knowledge needed for CGRP antagonism and (2) developmental
      issues of specific CGRP antagonists for provider use. This clinically oriented
      review documents IgG structure and function; state of the art of monoclonal IgG
      production and ligand-antigen-antibodies in migraine therapeutics contributing to
      immunogenic risks and off-target toxicities. Specifics to CGRP ligand, receptor,
      antagonism, and molecules, small and large, complete this review. Completion will
      facilitate assessment of the similarities, differences, and application of the
      forthcoming anti-CGRP receptor and ligand antagonists for patients.

PMID- 30187472
TI  - Altered T-cell subpopulations in recurrent pregnancy loss patients with cellular
      immune abnormalities.
AB  - Recurrent pregnancy loss (RPL) is a multifactorial disorder of women in
      reproductive age, which in some cases is caused by immunologic abnormalities. In
      this study, we aimed to evaluate cellular and molecular components of the immune
      system like different T-cell subsets and their regulating microRNAs (miRNAs) in
      RPL women and control group. Fifty RPL and 50 healthy subjects were recruited.
      Subsets of T cells, including regulatory T (Treg) cells, helper T (Th) 17 cells,
      exhausted T cells, exhausted Treg cells were evaluated by flow cytometry.
      Transcription factors of T cells and related miRNA profile were quantified using
      real-time polymerase chain reaction (RT-PCR). Assessment showed that Treg and
      exhausted T cells, were decreased in RPL patients (p = 0.009 and 0.02,
      respectively), while an increase was observed in Th17 and exhausted Treg
      frequency ( p = 0.013 and 0.0037, respectively). Messenger RNA expression level
      of T-bet and IRF4 was upregulated in RPL patients ( p = 0.011 and 0.0001,
      respectively), while Th2- and Treg-related transcription factors, GATA3 and GITR,
      were downregulated in these patients compared with the healthy subjects ( p =
      0.0008 and <0.000, respectively). Treg-associated miRNAs, the miR-106b-25-93
      cluster, showed a higher rate in RPL patients ( P = 0.007, 0.001, and 0.029,
      respectively), however, we observed no significant difference in the expression
      level of Th17-associated miRNA, mir-326. According to the results, we concluded
      that unbalanced immune responses and deregulated function of T-cell subsets may
      lead to reproduction-related failure like a miscarriage. Therefore, evaluation of
      immune cells and related miRNA profile may serve as prognostic biomarker for the
      treatment of RPL patients.

PMID- 30187473
TI  - Isolation and characterization of an aspartic protease able to hydrolyze and
      decolorize heme proteins from Aspergillus glaucus.
AB  - BACKGROUND: The xerophilic Aspergillus molds, Aspergillus glaucus and Aspergillus
      repens, have been used in the ripening and fermentation of dried tuna bonito
      (katsuobushi). These molds, and especially their extracellular hydrolytic
      enzymes, may also be of wider industrial value. RESULTS: Aspergillus glaucus
      strain MA0196 produces different types of hydrolytic enzymes, including amylase,
      serine protease, aspartic protease, lipase and cellulase, depending on the
      composition of the medium. We characterized several of these enzymes, focusing on
      a glycosylated aspartic protease. The results showed that the lower the d-glucose
      concentration in the medium, the higher the degree of protease glycosylation,
      with excess glycosylation tending to decrease protease activity. The molecular
      mass of the glycosylated protease as determined by gel filtration and sodium
      dodecyl sulphate-polyacrylamide gel electrophoresis was 243 and 253 kDa,
      respectively. The chemically deglycosylated protease had a molecular mass of only
      46 kDa. The amount of myoglobin-decolorizing activity was similar to that of a
      previously reported aspartic protease from A. repens strain MK82. However, the
      strain MA0196 protease more broadly hydrolyzed myoglobin and hemoglobins than did
      the strain MK82 protease. CONCLUSION: The results of the present study
      demonstrate the potential utility of Aspergillus molds as a functionally new
      microbial resource for industrial applications such as the bleaching of heme
      proteins. (c) 2018 Society of Chemical Industry.

PMID- 30187474
TI  - Synergistic interactions between konjac-mannan and xanthan/tragacanth gums in
      tomato ketchup: Physical, rheological, and textural properties.
AB  - In this research, simultaneous contribution of konjac-mannan (0.3%), xanthan
      (0.3%), and tragacanth (0.3%) gums in tomato ketchup was investigated comparing
      the physicochemical, rheological, texture, and sensory properties with the
      control sample containing 0.3% xanthan gum. Samples selected through viscosity
      and syneresis evaluation of the nine prepared samples were analyzed by color,
      flow behavior, frequency sweep, particle size, texture, and sensory experiments.
      Results indicated that increasing xanthan concentration did not have any
      significant effect on the apparent viscosity while considerable improvement was
      observed in the physical stability of ketchups containing konjac-mannan/xanthan
      ascribed to smaller particles with larger contact surfaces encouraging gel
      network formation. Highest a* and a*/b* was observed for konjac-mannan/xanthan
      (0.075%/0.225%) in which formation of hydrated gel granules of gums intensifies
      light diffraction due to the decreased particle size. This synergistically formed
      viscous three-dimensional gel network is responsible for the highest cohesiveness
      and gumminess of the same sample between the ketchup formulations containing two
      gums. Organoleptic properties of ketchup samples containing konjac-mannan/xanthan
      showed no significant difference with the control sample. PRACTICAL APPLICATIONS:
      Development of modern food technologies along with the lifestyle changes over the
      past few decades and grown public awareness of the relevance between health and
      nutrition have considerably increased the consumption of ready meals containing
      low-fat and fiber-rich functional condiments. Ketchup is a popular sauce
      thickened with tomato pulp powder, potato or corn starch, modified starch, and
      severally available hydrocolloids such as carboxymethyl cellulose, xanthan, guar,
      and locust bean gum. In this research work, mixtures of konjac-mannan and
      xanthan/tragacanth hydrocolloids are used to produce new ketchups with improved
      physical and rheological properties and lower prices.

PMID- 30187475
TI  - Effect of chitosan pre-soaking on the growth and quality of yellow soybean
      sprouts.
AB  - BACKGROUND: Soybeans are popularly known as a healthy food in many Asian
      countries and are mostly consumed as sprouts. The present study aimed to
      investigate the potential applications of chitosan as a natural growth regulator
      of soybean sprouts, as well as to determine the variation and composition of
      nutrients and anti-nutrients of soybean sprouts pre-soaked in different
      concentrations of chitosan solutions. RESULTS: The hypocotyl length and fresh
      weight of the soybean sprouts could be positively affected by chitosan treatment.
      The content changes of bioactive products in chitosan-soaked soybean sprouts were
      dependent on the concentration of chitosan and germination time. Additionally,
      the lowest phytic acid content was observed in 8 g kg-1 chitosan-treated soybean
      sprouts, and the phytic acid content values after 5 days of germination was 1.56
      g kg-1 , which was decreased by 79.0% compared to the value in ungerminated
      soybean. CONCLUSION: Chitosan pre-soaking can increase the hypocotyl length and
      fresh weight of soybean sprouts and also positively effect the content of
      bioactive products in sprouts, whereas phytic acid can be partially removed,
      thereby leading to the enhancement of product quality. Chitosan pre-soaking is an
      alternative technology for the production of low-cost functional foods, where the
      dose of chitosan is a key factor. (c) 2018 Society of Chemical Industry.

PMID- 30187476
TI  - Evaluation of anticancer effects of cerium oxide nanoparticles on mouse
      fibrosarcoma cell line.
AB  - Cerium oxide nanoparticles are associated with anticancer effects. While
      protecting normal cells, these nanoparticles exert their anticancer effects via
      oxidative stress and apoptosis in the cancer cells. In this study, the anticancer
      properties of nanoceria on fibrosarcoma cell line are evaluated. Cerium oxide
      nanoparticles were synthesized by the coprecipitation method and their anticancer
      effects on mouse fibrosarcoma tumor cells (WEHI164) were investigated. Viability
      assay was evaluated by MTT, and the DC-FDA assay performed for the detection of
      reactive oxygen species. For apoptosis assay, the annexin V/PI test was done as
      well as measuring the mRNA and protein expression levels of Bax and Bcl2 by real
      time PCR and western blot method, respectively. Characterization of nanoceria
      reveals that synthesized nanoceria has cubic floruit structure with a size of
      about 30 nm. Toxicity assessment results show that nanoceria increases ROS levels
      and induced apoptosis in a dose-dependent manner in cancer cells (WEHI164),
      whereas low levels of toxicity were observed in normal cells (L929), even at the
      concentrations above 250 ug/ml in MTT assay. Real-time PCR and western blot
      assays showed that nanoceria could significantly increase the Bax expression in
      cancer cells. The results showed that nanoceria could act as a potential
      therapeutic agent for the treatment of fibrosarcoma.

PMID- 30187477
TI  - Biocompatibility of alumina-based biomaterials-A review.
AB  - In today's medicine world, alumina-based biomaterials owing to their excellent
      biomechanical, and biocompatibility properties play a key role in biomedical
      engineering. However, the literature still suffers from not having a valid
      database regarding the protein adsorption and subsequently cell responses to
      these surfaces. Proteins by adsorption on biomaterials surfaces start
      interpreting the construction and also arranging the biomaterials surfaces into a
      biological language. Hence, the main concentration of this review is on the
      protein adsorption and subsequently cell responses to alumina's surface, which
      has a wide range biomedical applications, especially in dentistry and orthopedic
      applications. In the presented review article, the general principles of foreign
      body response mechanisms, and also the role of adsorbed proteins as key players
      in starting interactions between cells and alumina-based biomaterials will be
      discussed in detail. In addition, the essential physicochemical, and mechanical
      properties of alumina surfaces which significantly impact on proteins and cells
      responses as well as the recent studies that have focused on the biocompatibility
      of alumina will be given. An in depth understanding of how the immune system
      interacts with the surface of alumina could prove the pivotal importance of the
      biocompatibility of alumina on its success in tissue engineering after
      implantation in body.

PMID- 30187478
TI  - Effect of microfragmented adipose tissue on osteoarthritic synovial macrophage
      factors.
AB  - Cell-based therapies using adipose-derived mesenchymal stromal cells (ADMSCs)
      have shown promising results for the treatment of osteoarthritis (OA). In fact,
      ADMSCs are now indicated as one of the most powerful cell sources through their
      immunomodulatory and anti-inflammatory activities. Recently, an innovative one
      step closed device was developed to obtain microfragmented adipose tissue (MF) to
      avoid the need for good manufacturing practices for ADMSCs expansion while
      maintaining their regenerative potential. The aim of this study was to assess the
      mechanisms of action of MF and ADMSCs from MF (MF-ADMSCs) on an inflammatory cell
      model of OA synoviocytes. We found that MF produced low levels of inflammatory
      factors such as interleukin 6 (IL-6), CC-chemokine ligand 5/receptor-activated
      normal T-cell expressed and secreted (CCL5/RANTES), CC-chemokine ligand
      2/monocyte chemoattractant protein-1 (CCL2/MCP-1), and CC-chemokine ligand
      3/macrophage inflammatory protein-1alpha (CCL3/MIP-1alpha), and a higher level
      only of CXC-chemokine ligand 8/interleukin 8 compared with MF-ADMSCs. Matrix
      metalloproteinase 9 (MMP-9) degradative factor but released a lower level of its
      inhibitor tissue inhibitor of the metalloproteinase (TIMP-1). MF in coculture
      with synoviocytes significantly induced both the metabolic activity and the
      release of IL-6. In contrast, MF, not MF-ADMSCs, partially decreased CCL5/RANTES.
      Moreover, MF reduced the release of both macrophage-specific chemokines (CCL2/MCP
      1 and CCL3/MIP-1alpha) and degradative marker MMP-9. Interestingly, MF increased
      TIMP-1 (the MMP-9 inhibitor) and down-modulated toll-like receptor (TLR4)
      receptor and key molecules of NFkappaB pathways. These data evidenced different
      effects of MF versus MF-ADMSCs on inflamed synoviocytes. MF reduced typical
      macrophages markers and its potentiality by switching off macrophages activity
      was strictly dependent on TLR4 and NFkappaB signaling.

PMID- 30187479
TI  - Reply to Tsukuura et al: "Novel hands-free near-infrared fluorescence navigation
      and simultaneous combined imaging for the elevation of vascularized lymph node
      flap".

PMID- 30187480
TI  - Resveratrol ameliorates podocyte damage in diabetic mice via SIRT1/PGC-1alpha
      mediated attenuation of mitochondrial oxidative stress.
AB  - Excessive generation of mitochondrial reactive oxygen species (ROS) is considered
      to be initiating event in the development of diabetic nephropathy (DN).
      Mitochondrial biosynthesis mediated by coactivator PGC-1alpha and its downstream
      transcription factors NRF1 and TFAM may be a key target in maintaining
      mitochondrial function. Resveratrol (RESV), a natural polyphenolic antioxidant,
      is a potent SIRT1 agonist. In this study we established diabetes mouse and
      podocyte exposed to high glucose as in vivo and in vitro models to investigate
      the efficacy and mechanism of RESV on renoprotection. We found that RESV
      alleviated proteinuria of diabetic mice, decreased malondialdehyde content while
      increased Mn-SOD activity in renal cortex, inhibited the apoptosis of glomerular
      podocytes and renal tubular epithelial cells, ameliorated pathological
      manifestations, and restored the expression of SIRT1 and PGC-1alpha in renal
      tissues of DN mice. In podocytes exposed to high glucose, RESV inhibited
      excessive ROS production and apoptosis. In addition, RESV decreased mitochondrial
      ROS production, improved respiratory chain complex I and III activity, elevated
      mitochondrial membrane potential, and inhibited the release of Cyto C and Diablo
      in the mitochondria into the cytoplasm. Taken together, our findings suggest that
      RESV ameliorates podocyte damage in diabetic mice via SIRT1/PGC-1alpha mediated
      attenuation of mitochondrial oxidative stress.

PMID- 30187481
TI  - Bioinformatics analysis of microarray profiling identifies the mechanism of focal
      adhesion kinase signalling pathway in proliferation and apoptosis of breast
      cancer cells modulated by green tea polyphenol epigallocatechin 3-gallate.
AB  - OBJECTIVES: This study aimed to investigate potential gene and signal pathway
      associated with tumour progression. METHODS: Related microarray data set of
      breast cancer was obtained from Gene Expression Omnibus database, and
      differential-expressed genes (DEGs) between two control samples and two treated
      samples were analysed using statistical software R. We collected 50
      epigallocatechin-3-gallate(EGCG)-related genes and 119 breast cancer-related
      genes to create a knowledge base for following pathway analysis. KEY FINDINGS: A
      total of 502 mRNAs were identified as DEGs based on microarray analysis.
      Upregulated DEGs mainly enriched in nuclear nucleosome, cell adhesion, DNA
      packaging complex, Wnt-activated receptor activity, etc., while the downregulated
      DEGs significantly enriched in ncRNA processing, mitotic nuclear division, DNA
      helicase activity, etc. DEGs mostly enriched in gap junction, cell cycle,
      oxidative phosphorylation, focal adhesion, etc. EGCG suppressed FAK signalling
      pathway. Furthermore, EGCG could inhibit breast cancer cell proliferation and
      promote apoptosis by modulating CCND1. CONCLUSIONS: Epigallocatechin 3-gallate
      might exert influence on breast cancer progression through inhibiting focal
      adhesion kinase (FAK) signalling pathway.

PMID- 30187482
TI  - Multiple transcriptional regulation of walnut JrGSTTau1 gene in response to
      osmotic stress.
AB  - Glutathione S-transferases (GSTs) are important plant proteins involved in biotic
      and abiotic stress responses. A gene from Juglans regia, JrGSTTau1 was previously
      cloned and functionally characterized as an enzyme involved in improving cold
      tolerance in plants. To clarify the functional mechanism of JrGSTTau1 and its
      role in stress response, here, the JrGSTTau1 promoter including the up-stream
      regulators was examined using yeast one-hybrid together with transient expression
      assays, and the osmotic stress response ability was confirmed by comparing with
      wild-type plants. The 1500 bp JrGSTTau1 promoter displayed high GUS expression
      activity and was enhanced by mannitol stress. The promoter is composed of
      abundant cis-elements, some of which were osmotic stress response-related motifs,
      such as ABRE, DRE and MYB, indicating that the expression of JrGSTTau1 is
      regulated by potential up-stream regulators under abiotic stress. The
      transcription factors (TFs) of JrDREB2A, JrMYC2, JrMYB44, JrDof1 and JrWRKY7 were
      identified, which shared a similar response with JrGSTTau1 when exposed to
      PEG6000 in walnut leaf and root. These results implied that JrDREB2A, JrMYC2,
      JrMYB44, JrDof1 and JrWRKY7 may act as up-stream regulators of JrGSTTau1 to
      regulate or combine functionality with JrGSTTau1 in osmotic stress response.
      Furthermore, compared with the WT plants, the transgenic tobacco plants that
      overexpress JrGSTTau1 showed improved tolerance to drought induced by osmotic
      stress, in which antioxidant enzymes, proline and reactive oxygen species (ROS)
      are involved. Our results demonstrated the positive role played by JrGSTTau1 in
      osmotic tolerance, which is regulated by multiple up-stream regulators.

PMID- 30187483
TI  - Unresolved quenching mechanisms of chlorophyll fluorescence may invalidate MT
      saturating pulse analyses of photosynthetic electron transfer in microalgae.
AB  - Chlorophyll a fluorescence is a powerful tool for estimating photosynthetic
      efficiency, but there are still unanswered questions that hinder the use of its
      full potential. The present results describe a caveat in estimation of
      photosynthetic performance with so-called rapid light curves (RLCs) with pulse
      amplitude modulation fluorometers. RLCs of microalgae show a severe decrease in
      photosynthetic performance in high light, although a similar decrease cannot be
      seen with other methods. We show that this decrease cannot be assigned to energy
      dependent non-photochemical quenching or photoinhibition or to the geometry of
      the algal sample. The measured decrease in electron transfer rate is small in the
      tested siphonaceuous algae and higher plants, but very notable in all planktonic
      species, exhibiting species-dependent variation in extent and reversibility. We
      performed in-depth analysis of the phenomenon in the diatom Phaeodactylum
      tricornutum, in which the decrease is the most pronounced and reversible among
      the tested organisms. The results suggest that quenching of fluorescence by
      oxidized plastoquinone alone cannot explain the phenomenon, and alternative
      quenching mechanisms within PSII need to be considered.

PMID- 30187484
TI  - Comparative study of IDDSI flow test and line-spread test of thickened water
      prepared with different dysphagia thickeners.
AB  - The flow behaviors of thickened water samples prepared with six commercial
      instant thickeners (A-F) were investigated at different thickness levels using
      the inexpensive, simple, and visual clinical tools, such as a line-spread test
      (LST) and a syringe flow test developed by the International Dysphagia Diet
      Standardization Initiative (IDDSI). Both the flow distance value measured by the
      LST and the volume remaining in syringe by IDDSI flow test were compared with the
      apparent viscosity (etaa,50 ) values measured with a sophisticated computer
      controlled rheometer. The etaa,50 values of thickened water samples increased as
      thickener concentration increased, whereas the flow distance (cm; LST) or
      remaining volume (ml; IDDSI flow test) were decreased. Plots comparing etaa,50
      values to LST flow distances and IDDSI volumes revealed exponential relationships
      (R2  = 0.926 for the LST and R2  = 0.898 for IDDSI test) between the two
      measurements. Such lower determination coefficient (R2 ) values (0.898) by IDDSI
      flow test seems to be due to the stickiness characteristics of starch component
      in starch-based thickeners (E and F), indicating that the syringe flow test is
      not suitable for starch-based thickeners. However, the thickened water samples
      prepared only with xanthan gum (XG)-based thickeners (A-D) showed strong
      relationships (R2  = 0.972 for the LST and R2  = 0.939 for IDDSI test). These
      results suggest that the LST is a more reliable method than the IDDSI test for
      evaluating the correct and desirable viscosity for the dysphagia diet, and that
      the IDDSI test provides a means to predict the rheometer-measured viscosity of
      water thickened with only XG-based thickeners. PRACTICAL APPLICATIONS: The
      effective management of dysphagia requires the thickened fluids prepared with the
      correct and desirable viscosity. In terms of clinical practice, it is very
      important to observe the comparison of LST with IDDSI flow test to determine a
      suitable method for estimating the correct viscosity of thickened fluids. Our
      results showed good relationships between the rheometer-measured viscosity and
      flow values measured by the LST and IDDSI test methods for the thickened water
      samples prepared with different foods thickeners. The IDDSI flow test may be
      useful as a clinical training tool for preparing thickened fluids with only XG
      based thickeners to a target level of viscosity. These results presented in this
      study will provide clinicians, caregivers, and patients with valuable information
      for IDDSI flow test as an inexpensive and simple method for measuring the correct
      viscosity.

PMID- 30187485
TI  - The phosphorylation of Tudor-SN mediated by JNK is involved in the regulation of
      milk protein synthesis induced by prolactin in BMECs.
AB  - Tudor staphylococcal nuclease (Tudor-SN) is a multifunctional protein involved in
      a variety of cellular processes and plays a critical role in the regulation of
      gene expression. Recently, Tudor-SN was found to be upregulated in mammary
      epithelial cells during lactation in response to prolactin, which further to
      regulate milk protein synthesis. However, the detailed regulatory mechanism of
      Tudor-SN to milk protein still remains to be elucidated. In our study, we
      observed that the levels of Tudor-SN and phosphor-Tudor-SN (Thr103) were both
      enhanced upon prolactin stimulation. Immunofluorescence assays demonstrated that
      prolactin treatment facilitated the nuclear transport of Tudor-SN. Further study
      revealed that the phosphorylation of Tudor-SN was depended on activated JNK.
      Coimmunoprecipitation assays disclosed that Tudor-SN might be phosphorylated
      directly by JNK. Using gene mutation assays, we further discovered that mutation
      of Thr to Ala at site of 103 prevented the nuclear transport of Tudor-SN. Thus,
      these results suggested the essential mechanism of the activated Tudor-SN in milk
      protein regulation in response to prolactin, which may provide some new sights
      into improve milk protein production.

PMID- 30187486
TI  - The combination of K+ deficiency with other environmental stresses: what is the
      outcome?
AB  - Potassium (K+ ) is a macronutrient known for its high mobility and positive
      charge, which allows efficient and fast control of the electrical balance and
      osmotic potential in plant cells. Such features allow K+ to remarkably contribute
      to plant stress adaptation. Some agricultural lands are deficient in K+ ,
      imposing a stress that reduces crop yield and makes fertilization a common
      practice. However, individual stress conditions in the field are rare, and crops
      usually face a combination of different stresses. As plant response to a stress
      combination cannot always be deduced from individual stress action, it is
      necessary to gain insights into the specific mechanisms that connect K+
      homeostasis with other stress effects to improve plant performance in the context
      of climate change. Surprisingly, plant responses to environmental stresses under
      a K+ -limiting scenario are poorly understood. In the present review, we
      summarize current knowledge and find substantial gaps regarding specific outcomes
      of K+ deficiency in addition to other environmental stresses. In this regard,
      combined nutrient deficiencies of K+ and other macronutrients are covered in the
      first part of the review and interactions arising from K+ deficiency with
      salinity, drought and biotic factors in the second part. Information available so
      far suggests a prominent role of potassium and nitrate transport systems and
      their regulatory proteins in the response of plants to several stress
      combinations. Thus, such molecular pathways, which are located at the crossroad
      between K+ homeostasis and environmental stresses, could be considered
      biotechnological targets in future studies.

PMID- 30187487
TI  - Signaling-chemokine axis network in brain as a sanctuary site for metastasis.
AB  - BACKGROUND: Brain metastasis remains a major cause of death in patients with
      solid cancers. The co-operation between several molecular factors such as
      chemokines, chemokine receptors, and signaling pathways is involved in the
      pathogenesis of brain metastasis mostly from solid tumors. In this review, we
      examine the possible role of chemokine/receptor axis, as well as signaling
      pathways as prognostic biomarkers in brain metastasis. METHODS: Relevant English
      language literature were searched and retrieved from Google Scholar search engine
      (1993-2017). The following keywords were used: "chemokine," "signaling pathway,"
      "brain," "metastasis," and "niche." RESULTS: Increased expression of chemokines
      like CXCL12 and dysregulated signaling intermediates such as Notch in patients
      with solid tumors (e.g., breast cancer) is associated with brain metastasis.
      CONCLUSIONS: As biomarkers for brain metastasis, chemokine, and signaling
      intermediates are potential prognostic factors in a number of solid tumor,
      including breast cancer, melanoma, and lung cancer.

PMID- 30187488
TI  - Phytochemistry and pharmacology of the genus Entandrophragma over the 50 years
      from 1967 to 2018: a 'golden' overview.
AB  - OBJECTIVES: For centuries, the genus Entandrophragma (Meliaceae), endemic to
      Africa, has been used in traditional medicine for the treatment of several
      illnesses. This review deals with large range of phytochemicals from the genus
      Entandrophragma and their pharmacological potentials covering the period from
      1967 to 2018. KEY FINDINGS: Phytochemical investigations of the genus
      Entandrophragma led to the report of about 166 secondary metabolites which have
      been thoroughly summarized herein including some of their semisynthetic
      derivatives obtained from chemical transformations as well as their biological
      activities in the medicinal and agricultural domains. The limonoids or meliacins
      and their precursor called protolimonoids (protomeliacins) reported so far
      represent almost 69.28% of the total secondary metabolites obtained from the
      genus, and they display the most potent biological activities. Collectively, both
      classes of metabolites constitute the markers of Entandrophragma. However,
      squalene-type triterpenoids and sesquiterpenoids were reported only from the
      species E. cylindricum and therefore could be its chemotaxonomic markers.
      SUMMARY: The pharmacological investigations of the extracts of some species
      exhibited interesting results which support the traditional uses of these
      Entandrophragma plants in folk medicine. Some compounds revealed promising
      antiplasmodial and anti-inflammatory activities and deserve therefore further
      attention for new drug discovery.

PMID- 30187489
TI  - Tissue-specific hormone profiles from woody poplar roots under bending stress.

PMID- 30187490
TI  - Role of green tea catechins in prevention of age-related cognitive decline:
      Pharmacological targets and clinical perspective.
AB  - Over the past decade, a wide range of scientific investigations have been
      performed to reveal neuropathological aspects of cognitive disorders; however,
      only limited therapeutic approaches currently exist. The failures of conventional
      therapeutic options as well as the predicted dramatic rise in the prevalence of
      cognitive decline in the coming future show the necessity for novel therapeutic
      agents. Recently, a wide range of research has focused on pharmacological
      activities of green tea catechins worldwide. Current investigations have
      clarified mechanistic effects of the catechins in inflammatory cascades,
      oxidative damages, different cellular transcription as well as transduction
      pathway in various body systems. It has been demonstrated that green tea
      polyphenols prevent age-related neurodegeneration through improvement of
      endogenous antioxidant defense mechanisms, modulation of neural growth factors,
      attenuation of neuroinflammatory pathway, and regulation of apoptosis. The
      catechins exhibited beneficial effects in cellular and animal models of
      neurodegenerative diseases including Alzheimer's disease, MS, and Parkinson's
      disease. The present review discusses the current pharmacological targets, which
      can be involved in the treatment of cognitive decline and addresses the action of
      catechin derivatives elicited from green tea on the multiple neural targets.

PMID- 30187491
TI  - Silence of long intergenic noncoding RNA HOTAIR ameliorates oxidative stress and
      inflammation response in ox-LDL-treated human macrophages by upregulating miR-330
      5p.
AB  - Evidence of the involvement of long noncoding RNAs (lncRNAs) in atherosclerosis
      is growing but still not well characterized. Here, we concentrated on the
      biological roles of lncRNA HOX transcription antisense RNA (HOTAIR) in
      atherosclerosis. In our study, we found that oxidized low-density lipoprotein (ox
      LDL) induced human macrophages THP-1 cells apoptosis dose dependently and time
      dependently. Meanwhile, HOTAIR was significantly increased in THP-1 cells treated
      with ox-LDL. Then, HOTAIR was modulated by infection of LV-short hairpin RNA
      (shRNA) and LV-HOTAIR into THP-1 cells. As displayed, CD36, Oil Red O staining
      levels, total cholesterol, triglyceride levels and dil-ox-LDL uptake rate were
      greatly repressed by the silence of HOTAIR while triggered by overexpression of
      HOTAIR. Moreover, knockdown of HOTAIR suppressed reactive oxygen species,
      malondialdehyde levels, increased superoxide dismutase activity and cell
      apoptosis were also restrained. Reversely, overexpression of HOTAIR exhibited an
      opposite phenomenon. In addition, interleukin 6 (IL-6), IL-1beta, cyclo-oxygenase
      2, and tumor necrosis factor alpha protein levels were significantly depressed by
      LV-shRNA) of HOTAIR while increased by upregulation of HOTAIR in THP-1 cells. By
      carrying out bioinformatics analysis, miR-330-5p was predicted as a target of
      HOTAIR and the correlation between them was validated in our current study. MiR
      330-5p was greatly decreased in THP-1 cells incubated with ox-LDL and
      overexpression of miR-330-5p was able to inhibit oxidative stress and
      inflammation process. Taken together, it was implied that HOTAIR contributed to
      atherosclerosis development by downregulating miR-330-5p in human macrophages.

PMID- 30187492
TI  - Comparative efficacy of agricultural by-products in sequestering mycotoxins.
AB  - BACKGROUND: Biosorption using agricultural by-products has been proven as a low
      cost and safe way to sequester mycotoxins. Few agricultural by-products have been
      studied for their efficacy in adsorbing simultaneously a large range of
      mycotoxins. The present work compared the ability of 51 agricultural by-products
      to adsorb mycotoxins from liquid mediums simulating physiological pH values, and
      it studied the mechanism for mycotoxin adsorption by isotherm adsorption
      experiments. RESULTS: Grape pomaces, artichoke wastes, and almond hulls were
      selected as promising biosorbents for mycotoxins, being quite effective towards
      aflatoxin B1 (AFB1 ), zearalenone (ZEA), and ochratoxin A (OTA). Their adsorption
      was not affected by medium pH, and the adsorbed fraction was not released when pH
      rose from acid to neutral values. Fumonisin B1 (FB1 ) was adsorbed to a lesser
      extent, and deoxynivalenol adsorption was not recorded. For the selected
      biosorbents, maximum adsorption capacity calculated by the best fitting model
      (Freundlich, Langmuir, or Sips equation) ranged from 1.2 to 2.9 ug mg-1 for AFB1
      , 1.3 to 2.7 ug mg-1 for ZEA, 0.03 from 2.9 ug mg-1 for OTA, and 0.01-1.1 ug mg-1
      for FB1 . CONCLUSION: This study confirms that some agricultural by-products can
      find technological applications as feed/food additives for mycotoxin reduction.
      (c) 2018 Society of Chemical Industry.

PMID- 30187493
TI  - Mango phenolics increase the serum apolipoprotein A1/B ratio in rats fed high
      cholesterol and sodium cholate diets.
AB  - BACKGROUND: Serum lipoproteins are in dynamic equilibrium, partially controlled
      by the apolipoprotein A1 to apolipoprotein B ratio (APOA1/APOB). Freeze-dried
      mango pulp (FDM) is a rich source of phenolic compounds (MP) and dietary fiber
      (MF), although their effects on lipoprotein metabolism have not yet been studied.
      RESULTS: Thirty male Wistar rats were fed with four different isocaloric diets
      (3.4 kcal g-1 ) for 12 weeks: control diet, high cholesterol (8 g kg-1 ) + sodium
      cholate (2 g kg-1 ) diet either alone or supplemented with MF (60 g kg-1 ), MP (1
      g kg-1 ) or FDM (50 g kg-1 ). MP and FDM reduced food intake, whereas MF and MP
      tended to increase serum APOA1/APOB ratio, independently of their hepatic gene
      expression. This suggests that lipoprotein metabolism was favorably altered by
      mango bioactives, MP also mitigated the non-alcoholic steatohepatitis that
      resulted from the intake of this diet. CONCLUSION: We propose that phenolics are
      the most bioactive components of mango pulp, acting as anti-atherogenic and
      hepatoprotective agents, with a mechanism of action tentatively based on changes
      to the main protein components of lipoproteins. (c) 2018 Society of Chemical
      Industry.

PMID- 30187494
TI  - Novel hands-free near-infrared fluorescence navigation and simultaneous combined
      imaging for elevation of vascularized lymph node flap.

PMID- 30187495
TI  - Regulation of flowering by green light depends on its photon flux density and
      involves cryptochromes.
AB  - Photoperiodic lighting can promote flowering of long-day plants (LDPs) and
      inhibit flowering of short-day plants (SDPs). Red (R) and far-red (FR) light
      regulate flowering through phytochromes, whereas blue light does so primarily
      through cryptochromes. In contrast, the role of green light in photoperiodic
      regulation of flowering has been inconsistent in previous studies. We grew four
      LDP species (two petunia cultivars, ageratum, snapdragon and Arabidopsis) and two
      SDP species (three chrysanthemum cultivars and marigold) in a greenhouse under
      truncated 9-h short days with or without 7-h day-extension lighting from green
      light (peak = 521 nm) at 0, 2, 13 or 25 MUmol m-2  s-1 or R + white (W) + FR
      light at 2 MUmol m-2  s-1 . Increasing the green photon flux density from 0 to 25
      MUmol m-2  s-1 accelerated flowering of all LDPs and delayed flowering of all
      SDPs. Petunia flowered similarly fast under R + W + FR light and moderate green
      light but was shorter and developed more branches under green light. To be as
      effective as R + W + FR light, saturation green photon flux densities were 2
      MUmol m-2  s-1 for LDP ageratum and SDP marigold and 13 MUmol m-2  s-1 for LDP
      petunia. Snapdragon was the least sensitive to green light. In Arabidopsis,
      cryptochrome 2 mediated promotion of flowering under moderate green light,
      whereas both phytochrome B and cryptochrome 2 mediated that under R + W + FR
      light. We conclude that 7-h day-extension lighting from green light-emitting
      diodes can control flowering of photoperiodic ornamentals and that in
      Arabidopsis, cryptochrome 2 mediates promotion of flowering under green light.

PMID- 30187496
TI  - Management of adverse events associated with idelalisib treatment in chronic
      lymphocytic leukemia and follicular lymphoma: A multidisciplinary position paper.
AB  - The introduction of new therapeutic agents in chronic lymphocytic leukemia (CLL)
      and follicular lymphoma (FL), including the new kinase inhibitor idelalisib, has
      changed the therapeutic landscape of these diseases. However, the use of
      idelalisib is associated with a peculiar profile of side effects, which require
      an optimization of the current approach to prophylaxis and supportive treatment.
      Moving from the recognition that the abovementioned issue represents an unmet
      need in CLL and FL, a multidisciplinary panel of experts was convened to produce
      a consensus document aiming to provide practical recommendations for the
      management of the side effects during idelalisib therapy for CLL and FL. The
      present publication represents a consensus document from a series of meetings
      held during 2017. The Panel generated clinical key questions using the criterion
      of clinical relevance through a Delphi process and explored 4 domains, ie,
      diarrhea/colitis, transaminitis, pneumonitis, and infectious complications. Using
      the consensus method, the Panel was able to shape recommendations which may
      assist hematologist to minimize adverse events and guarantee adherence to
      treatment in patients with CLL and FL candidate to receive idelalisib.

PMID- 30187497
TI  - Effect of negative motivation on the behavioral and autonomic correlates of
      deception.
AB  - In forensic contexts, lying is often motivated by the will to avoid negative
      consequences (e.g., an arrest). Previous research investigating the effect of
      motivation on deception has, however, nearly exclusively focused on the effect of
      positive motivation (e.g., via financial rewards). In the current study, we aimed
      to replicate previous studies on the behavioral and autonomic correlates of
      deception and to investigate the influence of negative motivation on those
      correlates. Participants committed a mock theft and underwent a questioning
      procedure in which they had to truthfully and deceptively answer questions about
      the committed mock crime and a control crime. Half of the participants completed
      the procedure without any specific motivation, whereas the other half of the
      participants was told that lies detected by a computer algorithm would result in
      an unpleasant electric stimulation. Results revealed longer reaction times,
      larger skin conductance responses, and a relative heart rate slowing for lying
      compared to truth telling. The latter two effects were larger in the motivation
      compared to the control condition. Results are in line with the motivation
      impairment hypothesis and effects of positive motivation on the autonomic
      correlates of information concealment. The observation that a higher motivation
      increased rather than decreased deception effects is promising for forensic
      contexts. The possible explanation that these effects could be related to fear
      conditioning should stimulate future research on the stability of differences
      between lying and truth telling in people who experienced no or only seldom
      punishment for deception in their learning history.

PMID- 30187498
TI  - Cultural equivalence, reliability and utility of the Portuguese version of the
      Oral Behaviours Checklist.
AB  - BACKGROUND: Oral behaviors (OBs) must be assessed as part of a biobehavioural
      evaluation for patients with temporomandibular disorders (TMD). OBJECTIVES: The
      aims of this study were: to translate and culturally adapt the Oral Behaviors
      Checklist (OBC) into Portuguese; to evaluate its basic psychometric properties;
      and to assess the utility of the Portuguese OBC. METHODS: The Portuguese
      translation, cross-cultural equivalence, and two studies (Pre-field test, N = 8,
      and field test, N = 45) of the OBC adhered to official guidelines of the
      International RDC/TMD Research Consortium (now, INfORM). In the formal test (N =
      120) the Portuguese RDC/TMD was used for TMD diagnosis. RESULTS: Translation and
      cultural equivalence of the OBC into Portuguese was reviewed and approved by an
      expert panel. In the field test, item agreement between English and Portuguese
      OBC versions was very good (weighted Kappa >= 0.934). Test-retest reliability of
      the OBCS umScore was excellent intra-class correlation coefficient ((ICC) =
      0.998, P < 0.001). As an initial probe into validity using parallel forms,
      comparison of the sleep bruxism and awake clenching questions included in the
      RDC/TMD with the corresponding OBC questions yielded excellent (Kappa = 0.932)
      and very good (k = 0.850), respectively, convergent validity as well as excellent
      (that is, poor agreement, kappa = 0.013) discriminant validity for these specific
      OBs. The mean OBCS umScore was significantly lower for the healthy group,
      compared to the painful TMD group (ANOVA, P = 0.037). CONCLUSIONS: The Portuguese
      translation of the OBC exhibits cross-cultural equivalence for use in Portugal,
      and the instrument performs with acceptable psychometric properties. The validity
      of the parafunction construct requires additional research in both Portuguese and
      other languages.

PMID- 30187499
TI  - A case of bullous eruptive disseminated porokeratosis.

PMID- 30187500
TI  - Electric field assisted transport of dielectric droplets dispersed in aqueous
      solutions of ionic surfactants.
AB  - Motion of liquid droplets with a surface electric charge can be efficiently
      controlled by dc electric field. Here, we show that the surface of a dielectric
      kerosene droplet can be charged by the addition of ionic surfactants to a
      surrounding aqueous electrolyte. The direction of droplet motion is determined by
      the polarity of the surfactant charge and the orientation of the imposed electric
      field. We have found that the effective electrophoretic mobility of dielectric
      droplets in a confined channel is directly proportional to the logarithm of the
      surfactant concentration even for values significantly exceeding critical micelle
      concentration (CMC). We attribute this finding not only to adsorption of ionic
      surfactants to the surface of dielectric droplets but also to the weakening of
      electro-osmosis at channel walls due to the increase of ionic strength in the
      aqueous phase. Our findings can be exploited in microfluidic reactors and
      separators for on request dosing, sampling, and separation of dielectric fluids.

PMID- 30187501
TI  - Solid carcinoma is a variant of microcystic adnexal carcinoma: A 14-case series.
AB  - BACKGROUND: Solid carcinoma is a poorly characterized malignant apocrine neoplasm
      as only 16 cases have been published. OBJECTIVE: To characterize its clinical,
      histopathological, and immunohistochemical features. METHODS: We compiled 14
      cases of solid carcinoma and clinical information were updated. Hematoxylin and
      eosin slides were reviewed and we stained all the cases for CEA, EMA, SMA, PHLDA
      1, BerP4, nestin, p53, p63, p75, CK5/6, CK7 and some with remaining material for
      CK14, 15, CK10, CK19, S100, CD117, and CAM5. RESULTS: All the lesions were
      located on the scalp. Histopathologically, all the cases were characterized by
      solid aggregates of neoplastic epithelial cells without nuclear atypia or mitotic
      figures involving all the dermis. All the cases presented perineural infiltration
      and most of them had cornified cystic structures. CK5/6 and p63 were positive.
      CEA and EMA underlined the scarce ducts. Ki67 was lower than 1%. BerEP4 and PHLDA
      1 were negative. CONCLUSION: Solid carcinoma is a solid variant of MAC affecting
      the scalp more frequently than classic MAC, mostly in old males and showing
      variable-sized nests involving the entire dermis and composed by poroid, clear
      cells, or a mixture of both. It is positive for p63 and CK5/6 and negative for
      BerEP4 and PHLDA-1. Staining features with CK19 and PHLDA1 differ from classic
      MAC.

PMID- 30187502
TI  - Irreversible effects of trichloroethylene on the gut microbial community and gut
      associated immune responses in autoimmune-prone mice.
AB  - The developing immune system is particularly sensitive to immunotoxicants. This
      study assessed trichloroethylene (TCE)-induced effects on the gut microbiome and
      cytokine production during the development in mice. Mice were exposed to TCE
      (0.05 or 500 MUg/mL) at the levels that approximate to environmental or
      occupational exposure, respectively. Mice were subjected to a continuous
      developmental exposure to these doses encompassing gestation, lactation and
      continuing directly in the drinking water postnatally for 154 days (PND154) or
      PND259. To observe persistence of the effect TCE was removed from the drinking
      water in a subset of mice on PND154 and were provided regular drinking water
      until the study terminus (PND259). Abundance of total tissue-associated bacteria
      reduced only in mice exposed to TCE until PND259. The ratio of
      Firmicutes/Bacteroidetes did not alter during this continuos exposure; however,
      cessation of high-dose TCE at PND154 resulted in the increased abundance
      Bacteroidetes at PND259. Furthermore, high-dose TCE exposure until PND259
      resulted in a lower abundance of the genera Bacteroides and Lactobaccilus and
      increased abundance of genus Bifidobactrium and bacterial family
      Enterobacteriaceae. TCE exposure until PND154 showed significant changes in the
      production of interleukin-33; that might play a dual role in maintaining the
      balance and homeostasis between commensal microbiota and mucosal health. At
      PND259, interleukin-3, granulocyte-macrophage colony-stimulating factor and
      Eotaxin were altered in both, the continuous exposure and cessation groups,
      whereas only a cessation group had a higher level of KC that may facilitate
      infiltration of neutrophils. The irreversible effects of TCE after a period of
      exposure cessation suggested a unique programming and potential toxicity of TCE
      even at the environmental level exposure.

PMID- 30187503
TI  - Unexpected finding of uniparental disomy mosaicism in term placentas: Is it a
      common feature in trisomic placentas?
AB  - OBJECTIVE: Non-invasive prenatal testing (NIPT) detects placental chromosome
      aberrations. When amniocentesis reveals a normal karyotype, confined placental
      mosaicism (CPM) may be assumed. In order to confirm this, placental cytogenetic
      studies were performed. METHOD: NIPT was conducted in the course of the Dutch
      TRIDENT study. Placentas of 10 cases with NIPT results indicating an autosomal
      trisomy and showing a normal (N = 9) or low mosaic karyotype (N = 1) in amniotic
      fluid (AF) were investigated. The cytotrophoblast as well as the mesenchymal core
      of two to four placental chorionic villi biopsies were studied with single
      nucleotide polymorphism (SNP) array. Clinical outcome data were collected.
      RESULTS: In 10/10 cases, CPM was proven. In 3/10 cases trisomy/uniparental disomy
      (UPD)/biparental disomy (BPD) mosaicism was discovered. In 2/3 cases, all three
      cell lines were present in the placenta, whereas BPD was found in AF. In 1/3
      cases trisomy 22/UPD22 was present in AF while trisomy 22/BPD22 mosaicism was
      found in the placenta. Five of 10 pregnancies were affected with pre-eclampsia,
      low birth weight, preterm delivery, and/or congenital malformations. CONCLUSION:
      The presence of trisomy/UPD/BPD mosaicism in 3/10 cases that we investigated
      proves that trisomic zygote rescue may involve multiple rescue events during
      early embryogenesis. UPD mosaicism, when present in crucial fetal tissues, may
      explain the abnormal phenotype in undiagnosed cases.

PMID- 30187504
TI  - Impact of administration mode on Oro-facial Appearance assessment using the Oro
      facial Esthetic Scale.
AB  - BACKGROUND: Oro-facial Appearance is increasingly recognised as an important
      component of patient-reported outcomes in dentistry. While the Oro-facial
      Esthetic Scale (OES) has sufficient psychometric properties to characterise
      dental patient's global assessment of Oro-facial Appearance, the equivalence of
      alternative methods of administration has not been demonstrated so far.
      OBJECTIVE: Aim of this study was to investigate whether and to what extent method
      of administration affects OES scores. METHODS: Participants were recruited as
      convenience sample of 42 adult dental patients registered for a regular recall
      visit and with no actual need of dental interventions. Oro-facial Appearance was
      assessed using the German version of the OES applying three methods of
      administration: (a) face-to-face interview, (b) self-administered questionnaire
      and (c) telephone interview, in a randomised order with a period of about one
      week between assessments. RESULTS: Oro-facial Esthetic Scale summary scores did
      not differ substantially or statistically significantly between the different
      methods of administration (two-way ANOVA; P = 0.209). Intraclass correlation
      coefficients (ICC) for pairwise comparisons of administration modes ranged from
      0.67 to 0.84 indicating fair to excellent test-retest reliability. Internal
      consistency was satisfactory with lower limits of the 95% confidence interval
      (CI) of Cronbach's alpha ranging from 0.82 to 0.88 for the administration modes.
      Correlations of the OES summary score with a single item assessing global Oro
      facial Appearance supported convergent validity with lower limits of the CI of
      the correlation coefficients ranging between 0.58 and 0.75. CONCLUSION: The
      administration mode has no significant impact on Oro-facial Appearance assessment
      when using the OES.

PMID- 30187506
TI  - An acral papulovesicular eruption.

PMID- 30187505
TI  - Use of a random effects meta-analysis in the design and analysis of a new
      clinical trial.
AB  - In designing a randomized controlled trial, it has been argued that trialists
      should consider existing evidence about the likely intervention effect. One
      approach is to form a prior distribution for the intervention effect based on a
      meta-analysis of previous studies and then power the trial on its ability to
      affect the posterior distribution in a Bayesian analysis. Alternatively, methods
      have been proposed to calculate the power of the trial to influence the "pooled"
      estimate in an updated meta-analysis. These two approaches can give very
      different results if the existing evidence is heterogeneous, summarised using a
      random effects meta-analysis. We argue that the random effects mean will rarely
      represent the trialist's target parameter, and so, it will rarely be appropriate
      to power a trial based on its impact upon the random effects mean. Furthermore,
      the random effects mean will not generally provide an appropriate prior
      distribution. More appropriate alternatives include the predictive distribution
      and shrinkage estimate for the most similar study. Consideration of the impact of
      the trial on the entire random effects distribution might sometimes be
      appropriate. We describe how beliefs about likely sources of heterogeneity have
      implications for how the previous evidence should be used and can have a profound
      impact on the expected power of the new trial. We conclude that the likely causes
      of heterogeneity among existing studies need careful consideration. In the
      absence of explanations for heterogeneity, we suggest using the predictive
      distribution from the meta-analysis as the basis for a prior distribution for the
      intervention effect.

PMID- 30187507
TI  - Itching in a trichophytin contact dermatitis mouse model and the antipruritic
      effect of antifungal agents.
AB  - BACKGROUND: Tinea is an infectious disease by dermatophytes, of which
      Trichophyton species accounts for the overwhelming majority of case. Tinea often
      causes itching with inflammation. In terms of pruritus by fungal infection,
      however, tinea has not been investigated sufficiently to date. AIM: To evaluate
      itch caused by Trichophyton infection and the effect of antifungal agents on the
      infection, by measuring scratch behaviour and profiles of inflammatory cytokines
      and chemokines. METHODS: We used a previously established mouse model of contact
      hypersensitivity induced by trichophytin, a crude extract from Trichophyton
      mentagrophytes. Scratching behaviour was recorded using a counting device that
      measured an electric current induced in a coil by movement of magnets that had
      been inserted into the hind paws of each animal. We investigated expression of
      various genes in lesional skin of mice and in normal human epidermal
      keratinocytes. We also investigated the antipruritic effects of the
      corticosteroid dexamethasone (DEX) and three antifungal agents: ketoconazole
      (KCZ), terbinafine (TBF) and liranaftate (LNF). RESULTS: Biphasic peaks of
      scratching were observed at 1 h and at 6-7 h during an observation period of 14 h
      after trichophytin induction. For lesional skin, RNA was extracted 24 h after
      trichophytin challenge, and increased expression was seen in the genes for
      interleukin (IL)-17A, interferon-gamma, tumour necrosis factor (TNF)-alpha,
      macrophage inflammatory protein (MIP)-2 and Dectin-1, whereas there was no
      obvious change in the genes for IL-31 and prostaglandin (PG)E2. Furthermore, KCZ
      inhibited histidine decarboxylase (HDC) expression in vitro and in vivo, and
      inhibited scratching in the very early phase. LNF inhibited expression of thymic
      stromal lymphopoietin (TSLP) and IL-8 in vitro, and TSLP, TNF-alpha, IL-1alpha
      and MIP2 in vivo, and also scratching in the early phase. TBF did not induce any
      significant alterations in either gene expression or scratching. DEX suppressed
      expression of all the chemical mediators except HDC in vitro and in vivo, and
      inhibited scratching. CONCLUSION: Antifungals can inhibit itching induced by
      fungal infection through different mechanisms.

PMID- 30187508
TI  - Antibacterial activity of traditional spices against lower respiratory tract
      pathogens: combinatorial effects of Trachyspermum ammi essential oil with
      conventional antibiotics.
AB  - The aim of this study was to investigate the effects of ajowan essential oil
      (AjEO)/thymol and antibiotics combinations against three standard strains and six
      resistant clinical isolates of major respiratory bacteria (Pseudomonas
      aeruginosa, Staphylococcus aureus and Streptococcus pneumoniae). The broth
      microdilution method was conducted to determine the minimum inhibitory
      concentrations (MIC) of essential oil/thymol and antibiotics. The checkerboard
      method was used to investigate the interactions between the essential oil/thymol
      and antibiotics by means of the fractional inhibitory concentration index (FICI).
      The chemical composition of essential oil was also analysed by GC-MS and GC-FID.
      Thymol (50.75%), gamma-terpinene (25.94%) and p-cymene (18.31%) were identified
      as major constituents of the oil. The most sensitive organisms to ajowan volatile
      oil were Strep. pneumoniae bacteria (MIC = 0.125-0.5 mg ml-1 ). Synergistic
      effects were observed with AjEO/thymol and amoxicillin combinations on
      methicillin-resistant Staph. aureus clinical isolates (FICI = 0.37-0.50) and with
      essential oil and ciprofloxacin combinations against P. aeruginosa ATCC 27853,
      Staph. aureus ATCC 25923 and penicillin (P)-resistant Strep. pneumoniae bacteria
      (FICI = 0.37-0.50). Combination of thymol and ciprofloxacin produces synergistic
      effects only against P. aeruginosa ATCC 27853 and P-resistant Strep. pneumoniae
      clinical isolate (FICI = 0.46-0.49).

PMID- 30187509
TI  - Missed opportunities: unnecessary medicine use in patients with lung cancer at
      the end of life - an international cohort study.
AB  - AIMS: The aims of the current study were: (i) to examine the prescribing of
      preventative medication in a cohort of people with advanced lung cancer on
      hospital admission and discharge across different healthcare systems; and (ii) to
      explore the factors that influence preventative medication prescribing at
      hospital discharge. METHODS: A retrospective cohort study was conducted across
      two centres in the UK and the US. The prescribing of preventative medication was
      examined at hospital admission and discharge for patients who died of lung
      cancer. A zero-inflated negative binomial regression model was used to examine
      the association between preventative medications at discharge and patient- and
      hospital-based factors. The classes of preventative medication prescribed
      included were: vitamins and minerals, and antidiabetic, antihypertensive,
      antihyperlipidaemic and antiplatelet medications. RESULTS: In the UK site (n =
      125), the mean number of preventative medications prescribed was 1.9 [standard
      deviation (SD) 1.7) on admission, and 1.7 (SD 1.7) on discharge, and in the US
      site (n = 191) the mean was 2.6 (SD 2.2) on admission and 1.9 (SD 2.2) on
      discharge. The model found a significant association between the number of
      preventative drugs prescribed on admission and the number on discharge; it also
      found a significant association between the total number of drugs prescribed on
      discharge and the number of preventative medications on discharge. Other
      indicators related to patient and hospital factors were not significantly
      associated with the number of preventative medications supplied on discharge.
      CONCLUSIONS: The use of preventative medication was common in lung cancer
      patients, despite undergoing discharge. Patient- and hospital-based factors did
      not influence the prescribing of preventative medication.

PMID- 30187510
TI  - Effects of bisphenol A on gap junctions in HaCaT cells as mediated by the
      estrogen receptor pathway.
AB  - Bisphenol A (BPA) is widely used as the raw material for the production of
      plastics and paper products. People can be exposed to BPA through dermal contact,
      particularly for cashiers in contact with thermal paper every day. BPA is a known
      endocrine disruptor that has been shown to be carcinogenic. Many tumors show weak
      gap junctional intercellular communication (GJIC) function. The aim of this study
      was to investigate the effects and possible mechanisms of BPA's action on GJIC of
      human HaCaT skin cells. The results showed that BPA increased cell proliferation
      rates, prolonged GJIC photobleaching fluorescence recovery times and reduced
      overall fluorescence recovery rates at 0.01, 0.1 and 1 MUm. BPA downregulated
      connexin (Cx)26 mRNA level at 0.1 MUm. Estrogen receptor (ER) antagonist ICI 182
      780 at 5 nm partially blocked the above effects of BPA indicating involvement of
      the ER pathway with BPA exposure. However, BPA did not influence Cx43 mRNA and
      protein levels. Our immunofluorescence data showed that Cx26 was expressed in the
      cytoplasm and plasma membrane, and was involved in the formation of gap junctions
      between adjacent cells, while Cx43 was expressed only in the cytoplasm.
      Therefore, our data indicate that Cx26 gap junctions may be involved in the GJIC
      inhibition caused by BPA. In conclusion, our results indicate that BPA can
      promote human skin cell proliferation, inhibit skin cell GJIC function but not
      formation and downregulate Cx26 mRNA levels partially through the ER pathway. We
      hypothesize that BPA can exhibit carcinogenicity by inhibiting GJIC.

PMID- 30187511
TI  - Langerhans cell histiocytosis with prominent nail involvement.

PMID- 30187512
TI  - Leishmania infection activates host mTOR for its survival by M2 macrophage
      polarization.
AB  - Mammalian target of rapamycin (mTOR) is a central regulator of growth and
      immunity of host cells. It's involvement in cancer and tuberculosis is well
      documented but least explored in Leishmania donovani invasion of host cells.
      Therefore, in the present study, we aimed to investigate the role of mTOR in M2
      macrophage polarization for Leishmania survival. We observed that Leishmania
      infection activated host mTOR pathway characterized by phosphorylation of mTOR,
      70S6K and 4-EBP1. Inhibition of mTOR resulted in decreased parasite load and
      percent infectivity. Moreover, Leishmania infection triggered cell proliferation
      as was evidenced by increased expression of cyclin A and p-RPS6. mTOR activation
      during Leishmania infection resulted in reduced expression of M1 macrophage
      markers (eg, ROS, NO, iNOS, NOX-1, IL-12, IL-1beta and TNF-alpha), and increased
      expression of M2 macrophage markers (eg, arginase-1, IL-10, TGF-beta, CD206 and
      CD163). Furthermore, we observed that in case of Leishmania infection, mTOR
      inhibition increased the translocation of NF-kappaB to nucleus and deactivation
      of STAT-3. Eventually, we observed that inhibition of M2 macrophage polarization
      reduced Leishmania survival inside macrophages. Therefore, our findings suggest
      that mTOR plays a crucial role in regulation of M2 macrophage polarization and
      direct the innate immune homeostasis towards parasite survival inside host.

PMID- 30187513
TI  - Design Effect of Metallic (Durable) and Polymeric (Resorbable) Stents on Blood
      Flow and Platelet Activation.
AB  - Bioresorbable vascular scaffolds (BVS) provide transient vessel support for
      occluded coronary arteries while resorbing over time, potentially allowing vessel
      restoration approximating the native, healthy state. Clinical trials indicate
      that the Absorb BVS (Abbott Vascular, Santa Clara, CA) performance was similar to
      that of the Xience metallic drug-eluting stent (DES), with low long-term
      complications rates. However, when under-deployed in very small vessels (diameter
      < 2.25 mm), the thrombosis rate of BVS was higher, possibly due to the effect of
      strut thickness on the hemodynamics (157 MUm BVS vs. 81 MUm DES). This study aims
      to determine the influence of BVS design in vessels of varying diameter on the
      potential platelet activation. Sixteen computational fluid dynamics models of
      vessels of varying diameter (1.8-3.0 mm), strut thickness (81-157 MUm), and
      BVS/DES designs were compared. Platelet stress accumulation (SA), a metric for
      the activation potential, was calculated along platelet flow trajectories and
      their probability distribution was compared. The models were consistent with
      clinical observations, indicating that devices deployed in very small vessels
      exhibited increased probability for platelet activity as compared to the same
      devices deployed in nominal sized vessels. Deployment, although with residual
      stenosis, increased probability for higher SA than in similar diameter straight
      vessels. Reducing BVS struts thickness while maintaining their pattern improved
      performance closer to that of DES. Our findings highlight the importance of
      appropriate vessel sizing and deployment technique for BVS, and may help
      designing future BVS with thinner struts, ultimately improving performance in
      very small vessels.

PMID- 30187514
TI  - Attention difficulties and physical dysfunction common in children with complex
      congenital malformations: a study of preschool children with VACTERL association.
AB  - AIM: Knowledge on the neurodevelopmental and physical function in children with
      vertebral defects, anorectal malformations, cardiac defects, tracheo-oesophageal
      fistula, renal and limb malformations (VACTERL) is scarce. We evaluated Swedish
      preschool children with VACTERL and identified whether they would need extra
      support in school. METHODS: From 2015 to 2017, we recruited children aged 5-7
      with VACTERL association from the paediatric surgical centre at the University
      Children's Hospital at Uppsala. Neurodevelopmental function was assessed by age
      appropriate intelligence and visual and auditory attention tests, and the
      children's behaviour and attention were observed by an experienced psychologist.
      Physical function was evaluated through parental interviews and examinations.
      Data on patient characteristics, including any surgery and anaesthesia, were
      extracted from medical records. RESULTS: Of the 13 eligible families, 10 agreed
      to participate. Intelligence was within the normal range for all children, but
      attention difficulties were found in eight of the children, requiring adjustments
      at school, and two of these were later diagnosed with attention deficit
      hyperactivity disorder. All children had physical dysfunctions that affected
      their daily nutrition, bowel or bladder functions. CONCLUSION: Attention
      difficulties and physical dysfunction were common in Swedish preschool children
      aged 5-7 with VACTERL and they would need support and adjustments when they
      started school.

PMID- 30187515
TI  - The role of percutaneous vacuum-assisted thrombectomy for intracardiac and
      intravascular pathology.
AB  - Vacuum-assisted thrombectomy (VAT) is a mechanical suction device that can be
      deployed to aspirate thrombi in the heart and vascular system. Successful
      percutaneous aspiration of iliocaval, right heart, and pulmonary arterial thrombi
      have been reported, in addition to the debulking of intravascular and
      intracardiac masses and vegetations. VAT is indicated for patients who are poor
      surgical candidates and/or have a contraindication to thrombolysis. This review
      discusses the mechanism, current results, potential clinical indications, and
      limitations of VAT for iliocaval and intracardiac mass removal.

PMID- 30187516
TI  - Safety and benefits of new techniques and technologies in less invasive mitral
      valve repair.
AB  - OBJECTIVE: To assess the safety and benefits of new techniques and technologies
      such as single-dose (del Nido) cardioplegia and suture fasteners (COR-KNOT) in
      patients undergoing mini-thoracotomy for degenerative mitral valve repair (MVR).
      METHODS: From 2009 to 2016, 252 patients underwent primary isolated degenerative
      MVR by mini-thoracotomy by a single surgeon. Del Nido cardioplegia was used in
      153 patients (61%) and COR-KNOT in 168 (67%). Patient outcomes were compared
      using propensity-matching separately for del Nido versus Buckberg cardioplegia
      and COR-KNOT versus knot-pusher. RESULTS: There were no operative deaths and
      99.2% of the patients had none/trivial mitral regurgitation at discharge. In
      patients receiving del Nido or Buckberg cardioplegia, occurrence of adverse
      events was similar. However, aortic cross clamp (AoCC; 54.2 +/- 15.7 vs 64 +/-
      15.8 min; P < 0.0001) and operative room (OR; 308 +/- 42.1 vs 336 +/- 63 min; P <
      0.001) times were shorter with del Nido cardioplegia. In patients receiving COR
      KNOT versus knot-pusher, occurrence of adverse events was similar. However, AoCC
      (54.1 +/- 15.2 vs 66.1 +/- 15.9 min; P < 0.0001) and OR (311 +/- 43.6 vs 336 +/-
      65.4 min; P < 0.0001) times were shorter with COR-KNOT. Results were similar
      after matching for both, del Nido versus Buckberg cardioplegia and COR-KNOT
      versus knot-pusher. CONCLUSION: New techniques and technologies, such as del Nido
      cardioplegia and COR-KNOT, decrease AoCC and OR times without compromising
      patient safety.

PMID- 30187517
TI  - Pediatric Nasogastric Tube Placement and Verification: Best Practice
      Recommendations From the NOVEL Project.
AB  - The placement of a nasogastric tube (NGT) in a pediatric patient is a common
      practice that is generally perceived as a benign bedside procedure. There is
      potential risk for NGT misplacement with each insertion. A misplaced NGT
      compromises patient safety, increasing the risk for serious and even fatal
      complications. There is no standardized method for verification of the initial
      NGT placement or reverification assessment of NGT location prior to use.
      Measurement of the acidity or pH of the gastric aspirate is the most frequently
      used evidence-based method to verify NGT placement. The radiograph, when properly
      obtained and interpreted, is considered the gold standard to verify NGT location.
      However, the uncertainty regarding cumulative radiation exposure related to
      radiographs in pediatric patients is a concern. To minimize risk and improve
      patient safety, there is a need to identify best practice and to standardize care
      for initial and ongoing NGT location verification. This article provides
      consensus recommendations for best practice related to NGT location verification
      in pediatric patients. These consensus recommendations are not intended as
      absolute policy statements; instead, they are intended to supplement but not
      replace professional training and judgment. These consensus recommendations have
      been approved by the American Society for Parental and Enteral Nutrition (ASPEN)
      Board of Directors.

PMID- 30187518
TI  - Abstracts of Gastroenterological Society of Australia (GESA) Australian
      Gastroenterology Week (AGW) "Gut Matters" Brisbane Convention & Exhibition Centre
      Brisbane, Queensland 8-10 September 2018.

PMID- 30187519
TI  - Advanced endoscopic techniques.

PMID- 30187520
TI  - IBD Basic Science.

PMID- 30187521
TI  - Marital functioning and treatment outcome in couples undergoing assisted
      reproduction.
AB  - AIM: To investigate the relationship between the quality of marital functioning
      and communication, individual psychological symptomatology, and pregnancy
      achievement in couples undergoing assisted reproduction. BACKGROUND: The results
      concerning marital functioning and the feasibility of pregnancy yield
      contradictory outcomes and the quality of the relationship of the couple
      undergoing assisted reproduction has not been analysed from systemic models. Our
      hypothesis is that when undergoing assisted reproduction treatment (ART), the
      couple's functioning and communication will be related to the pregnancy rate.
      DESIGN: This study employs a cross-sectional design with couples receiving ART.
      METHODS: Spanish heterosexual couples (N = 185) completed the self-report
      instruments. The data were collected from 2010 - 2015. All the couples completed
      at least one treatment process, or at least 1 year had gone by since beginning
      the treatment. RESULTS: The association between couple relationship quality and
      the individual psychological symptomatology experienced during the assisted
      reproduction process was confirmed in men and women. Although both members of the
      couple experienced an increase of symptomatology, only men's symptomatology was
      statistically significantly linked to pregnancy achievement. CONCLUSION: It is
      necessary to support the couple from the assisted reproduction centres, promoting
      cohesion, flexibility, and communication in the relationship. The intervention
      process should also be understood from a systemic perspective; that is,
      considering dyadic transactions as a systemic unit. Two aspects seem to be
      especially relevant for clinical nurses in ART: (a) the man's role is crucial for
      treatment success; (b) the woman's communication is crucial to the process.

PMID- 30187522
TI  - Hommel's procedure in linear time.
AB  - Hommel's and Hochberg's procedures for familywise error control are both derived
      as shortcuts in a closed testing procedure with the Simes local test. Hommel's
      shortcut is exact but takes quadratic time in the number of hypotheses.
      Hochberg's shortcut takes only linear time after the P-values are sorted, but is
      conservative. In this paper, we present an exact shortcut in linear time on
      sorted P-values, combining the strengths of both procedures. The novel shortcut
      also applies to a robust variant of Hommel's procedure that does not require the
      assumption of the Simes inequality.

PMID- 30187523
TI  - Surgical treatment outcomes of infantile hemangioma in children: Does prior
      medical treatment matter.
AB  - First-line treatment for problematic infantile hemangiomas (IH) consists of
      systemic corticosteroids or, more recently, beta-blockers, while treatment
      failures or residual lesions may require surgical intervention. There is limited
      knowledge if prior medical intervention is associated with a better surgical
      outcome. This retrospective cohort study revealed that medical intervention,
      whether systemic steroids or beta-blockers, did not influence ultimate surgical
      outcomes when compared with patients who were not medically treated. However,
      patients who received prior medical treatment and those who received beta
      blockers underwent surgical intervention at an earlier age.

PMID- 30187524
TI  - Randomized double-blinded clinical trial of 5% dextrose versus triamcinolone
      injection for carpal tunnel syndrome patients.
AB  - OBJECTIVE: Perineural injection with 5% dextrose (D5W) is a novel strategy in the
      treatment of carpal tunnel syndrome (CTS). In contrast, perineural injection with
      corticosteroid has been used for decades for treating CTS, but possible
      neurotoxicity has been a major concern. No studies investigating the comparative
      effects have been published so far. The authors performed a prospective,
      randomized, double-blinded, head-to-head comparative trial to compare these two
      approaches for patients having mild-to-moderate CTS. METHODS: Fifty-four
      participants with mild-to-moderate CTS were randomly divided into dextrose and
      steroid groups. The patients were administered 1 session of perineural injection
      with 5ml D5W (dextrose group) or 3ml triamcinolone acetonide mixed with 2ml
      normal saline (steroid group), under ultrasound guidance. A visual analog scale
      was assigned to assess the primary outcome. The secondary outcomes were assessed
      using the Boston Carpal Tunnel Syndrome Questionnaire, cross-sectional area of
      the median nerve, and electrophysiological studies. The assessment was performed
      prior to injection and 1, 3, 4, and 6 months postinjection. RESULTS: All patients
      (27 wrists per group) completed the study. Compared with the steroid group, the
      dextrose group exhibited a significant reduction in pain and disability through
      the 4th to the 6th month (p < 0.01). INTERPRETATION: Our study demonstrates that
      perineural injection of D5W is more beneficial than that of corticosteroid in
      patients with mild-to-moderate CTS at 4 to 6 months postinjection. Ann Neurol
      2018;84:601-610.

PMID- 30187526
TI  - List of opinions of the Scientific Committee on Consumer Safety (SCCS) adopted
      and published January to August 2018.

PMID- 30187525
TI  - 30-year cross-sectional trends in waist-to-height ratio in Australian school age
      children; 1985 to 2015.
AB  - AIM: To report 30-year changes in the proportion of children with abdominal
      obesity measured by waist-to-height ratio (WHtR) >= 0.5. METHODS: Secondary
      analysis of WHtR >= 0.5 data on Australian children age 7 to 15 years from five
      national cross-sectional population surveys conducted in 1985, 1995, 2007, 2012
      and 2015. Changes in the proportions of children with a WHtR >= 0.5 across survey
      years, by age and sex were assessed using chi-squared tests. RESULTS: Between
      1985 and 2012, the proportion of children with WHtR >= 0.5 increased from 8.6%
      [95%CI: 8.0, 9.2] to 25.1% [95%CI: 23.5, 26.7]. An increase of ~5% each decade
      was observed between 1985 and 2007, and a 6.6% increase was observed between 2007
      and 2012. Overall, there was a non-significant decrease in the proportion of
      children with WHtR >= 0.5 between 2012 (25.1% [95%CI: 23.5, 26.7] and 2015 (23.3%
      [95%CI: 21.6, 25.2]. CONCLUSION: Abdominal obesity has increased over the last 30
      years in Australian children. In 2015, one in five children had WHtR >= 0.5, a
      marker of cardiometabolic risk in children. Our finding highlights the importance
      of including WHtR as a routine measurement in primary health care and population
      health surveys. This information is needed to guide policy and practice to manage
      long-term cardiovascular risk in children.

PMID- 30187527
TI  - Comparison of Tractography-Assisted to Atlas-Based Targeting for Deep Brain
      Stimulation in Essential Tremor.
AB  - BACKGROUND: Direct targeting of the dentato-rubro-thalamic tract is efficacious
      in DBS for tremor suppression. OBJECTIVES: We sought to compare outcomes and
      optimal stimulation parameters for tremor control using the technique of directly
      targeting the dentato-rubro-thalamic tract to those who underwent indirect
      targeting of the ventral intermediate nucleus thalamus. METHODS: Twenty
      consecutive essential tremor patients obtained preoperative diffusion MRIs, where
      the dentato-rubro-thalamic tract was individually drawn and used to directly
      target the ventral intermediate nucleus of the thalamus during surgery. These
      patients were compared to an earlier cohort of 20 consecutive patients who
      underwent surgery using atlas-based coordinates. Baseline and 1-year postsurgery
      tremor amplitude using The Essential Tremor Rating Assessment Scale was recorded,
      as were the parameters needed for successful tremor control. RESULTS: The
      indirectly targeted group had greater baseline and postop tremor severity
      relative to those directly targeted (baseline, 2.9 vs. 2.6; P = 0.02; postop, 1.1
      vs. 0.8; P = 0.03). Mean voltage, pulse width, and frequency for optimal tremor
      control in the directly targeted group (38 electrodes) = 2.8 V, 80 MUs, 153 Hz;
      the parameters for the indirectly targeted group (38 electrodes) = 2.9 V, 86 us,
      179 Hz (significantly greater, P < 0.001). Both groups had significant
      improvement in arm tremor amplitude from baseline (P < 0.001) without sustained
      side effects. CONCLUSION: Direct targeting of the dentato-rubro-thalamic tract
      provides excellent tremor control, comparable to indirectly targeting the ventral
      intermediate nucleus of the thalamus. Use of lower stimulation parameters,
      especially frequency, to control tremor in the directly targeted group suggests
      that it is a more efficient targeting methodology, which may minimize battery
      depletion. (c) 2018 International Parkinson and Movement Disorder Society.

PMID- 30187528
TI  - Improving oncological care organization in Poland-The 2015 reform evaluation in
      the context of European experiences.
AB  - Cancer is one of the leading causes of morbidity and mortality worldwide with a
      significant economic impact which has been increasing in recent decades. Numerous
      expert groups and/or international organizations have developed guidelines on how
      to build effective cancer control mechanisms, while in the European Union the
      majority of countries have developed national programmes. In Poland, cancer is
      the second leading cause of death. Compared with other European countries, Poland
      is characterized by a relatively low cancer incidence ratio, yet in terms of
      mortality and survival ratios, the situation is much worse than the average. On 1
      January 2015, an oncological therapy fast track was implemented in Poland,
      popularly known as the "oncological package." Its formal objectives were to
      improve access to and systemize the process of cancer diagnostics and treatment.
      The reform introduced some of the solutions existing in other European countries,
      including waiting time limits, patient pathways, multidisciplinary medical
      consultations, and a care coordinator position. The preliminary evaluation
      analyses suggest that after the reform implementation the average waiting time
      for diagnostics and treatment for patients covered by the new system was
      significantly shortened in comparison to those excluded. Further research
      evaluating the reform impact on quality and/or comprehensiveness of care are
      needed.

PMID- 30187530
TI  - Insecticide-induced changes in amphibian brains: How sublethal concentrations of
      chlorpyrifos directly affect neurodevelopment.
AB  - Widespread use of pesticides often contaminates natural habitats, exposing
      nontarget organisms to pesticides that were designed to control pest populations.
      Even low levels of pesticides can affect aquatic communities both directly and
      indirectly. Previous work has shown that trace amounts of the pesticide
      chlorpyrifos altered tadpole morphology and neurodevelopment in artificial ponds
      (mesocosms). To determine whether effects resulted from direct chlorpyrifos
      exposure or from disruption of the food web due to a pesticide-induced decline in
      zooplankton, we examined the impacts of chlorpyrifos on amphibian development in
      the presence of chlorpyrifos-resistant zooplankton, a key component of the
      aquatic trophic community. Northern leopard frog (Lithobates pipiens) tadpoles
      were reared through metamorphosis in mesocosms containing either 0 or 1 ug/L
      chlorpyrifos and either chlorpyrifos-resistant or chlorpyrifos-sensitive Daphnia
      pulex zooplankton. Developmental exposure to chlorpyrifos resulted in metamorphs
      with a relatively wider optic tectum, medulla, and diencephalon compared with
      controls, and this result was found regardless of the zooplankton population
      within the mesocosm. Thus, chlorpyrifos directly impacted brain development,
      independent of the effects on the trophic community. With respect to body shape,
      chlorpyrifos had no effect on body shape of metamorphs reared in mesocosms with
      chlorpyrifos-sensitive zooplankton, but body shape was sensitive to zooplankton
      population in the absence of chlorpyrifos. To conclude, low, ecologically
      relevant doses of organophosphorous pesticides can directly impact
      neurodevelopment in a vertebrate model. Environ Toxicol Chem 2018;37:2692-2698.
      (c) 2018 SETAC.

PMID- 30187529
TI  - Accuracy of elastic fusion biopsy in daily practice: Results of a multicenter
      study of 2115 patients.
AB  - OBJECTIVES: To assess the accuracy of Koelis fusion biopsy for the detection of
      prostate cancer and clinically significant prostate cancer in the everyday
      practice. METHODS: We retrospectively enrolled 2115 patients from 15 institutions
      in four European countries undergoing transrectal Koelis fusion biopsy from 2010
      to 2017. A variable number of target (usually 2-4) and random cores (usually 10
      14) were carried out, depending on the clinical case and institution habits. The
      overall and clinically significant prostate cancer detection rates were assessed,
      evaluating the diagnostic role of additional random biopsies. The cancer
      detection rate was correlated to multiparametric magnetic resonance imaging
      features and clinical variables. RESULTS: The mean number of targeted and random
      cores taken were 3.9 (standard deviation 2.1) and 10.5 (standard deviation 5.0),
      respectively. The cancer detection rate of Koelis biopsies was 58% for all
      cancers and 43% for clinically significant prostate cancer. The performance of
      additional, random cores improved the cancer detection rate of 13% for all
      cancers (P < 0.001) and 9% for clinically significant prostate cancer (P <
      0.001). Prostate cancer was detected in 31%, 66% and 89% of patients with lesions
      scored as Prostate Imaging Reporting and Data System 3, 4 and 5, respectively.
      Clinical stage and Prostate Imaging Reporting and Data System score were
      predictors of prostate cancer detection in multivariate analyses. Prostate
      specific antigen was associated with prostate cancer detection only for
      clinically significant prostate cancer. CONCLUSIONS: Koelis fusion biopsy offers
      a good cancer detection rate, which is increased in patients with a high Prostate
      Imaging Reporting and Data System score and clinical stage. The performance of
      additional, random cores seems unavoidable for correct sampling. In our
      experience, the Prostate Imaging Reporting and Data System score and clinical
      stage are predictors of prostate cancer and clinically significant prostate
      cancer detection; prostate-specific antigen is associated only with clinically
      significant prostate cancer detection, and a higher number of biopsy cores are
      not associated with a higher cancer detection rate.

PMID- 30187531
TI  - Missed diagnoses of abnormal copy number variant cases: A national epidemic or an
      endemic at a single institution?

PMID- 30187533
TI  - Response to comment on "Utility of novel fetal echocardiographic morphometric
      measures of the aortic arch in the diagnosis of neonatal coarctation of the
      aorta".

PMID- 30187532
TI  - Corrigendum for Arya, Bhat, Vernon, et al. (2015)
      https://doi.org/10.1002/pd.4753.

PMID- 30187535
TI  - Comment on "Utility of novel fetal echocardiographic morphometric measures of the
      aortic arch in the diagnosis of neonatal coarctation of the aorta".

PMID- 30187534
TI  - The epidemic of abnormal copy number variant cases missed because of reliance
      upon noninvasive prenatal screening.
AB  - OBJECTIVE: To assess the implications of increasing utilization of noninvasive
      prenatal screening (NIPS), which may reach 50% with the concomitant decrease in
      diagnostic procedures (DPs) for its impact on detection of chromosomal
      abnormalities. METHODS: We studied our program's statistics over 5 years for DPs
      and utilization of array comparative genomic hybridization (aCGH). We then
      modeled the implications in our program if DP had not fallen and nationally of a
      50% DP and aCGH testing rate using well-vetted expectations for the diagnosis of
      abnormal copy number variants (CNVs). RESULTS: Our DP fell 40% from 2013-2017.
      Utilization of aCGH for DP nearly tripled. We detected 28 abnormal CNVs. If DP
      had not fallen, we likely would have detected 60. With 4 million US births per
      year, 2 million DPs would detect 30 000 abnormal CNVs and 4000 standard
      aneuploidies. At a 1/500 complication-pregnancy loss rate, the
      detection/complication ratio is 8.5/1. CONCLUSIONS: Noninvasive prenatal
      screening has significantly changed the practice of prenatal screening. However,
      while increasing the detection of Down syndrome, the concomitant decrease in DP
      and lack of aCGH results in missing many more abnormalities than the increase in
      Down syndrome and complications of DP combined. From a public health perspective,
      such represents a missed opportunity for overall health care delivery.

PMID- 30187536
TI  - Developing a conceptual framework for patient safety culture in emergency
      department: A review of the literature.
AB  - Patient safety culture is a critical component of modern health care. However,
      the high-paced, unpredictable nature of the emergency department (ED) environment
      may impact adversely on it. The aim of this paper is to explore the concept of
      patient safety culture as it may apply to emergency health care, and to propose a
      conceptual framework that could form the basis for interventions designed to
      improve it. This is a systematic review of the literature. A search was
      undertaken of common electronic bibliographic databases using key words such as
      safety culture, safety climate, and Emergency Department. Articles were analysed
      for consistent themes with the aim to construct a conceptual framework. Ten
      articles met the inclusion criteria that specifically examined safety culture in
      the ED. Synthesis of the literature resulted in the emergence of three
      overarching themes of ED practice found to impact on safety culture in the ED.
      These were the dimensions of patient safety culture, the factors influencing it,
      and the interventions for improving it. A conceptual framework was constructed
      that identifies elements that significantly impact the patient safety culture in
      the ED. This framework may assist managers and researchers to take a
      comprehensive approach to build an effective safety culture in ED setting.

PMID- 30187537
TI  - Effectiveness of recruitment and retention strategies in a pregnant adolescent
      nutrition intervention study.
AB  - AIM: To report the methodological strategies used to recruit and retain pregnant
      adolescents into a nutrition-focused intervention study. BACKGROUND: An important
      step to meeting the developmental and healthcare needs of pregnant adolescents is
      to conduct high-quality research studies that generate reliable and accurate
      data. However, recruitment and retention of pregnant adolescents into research
      are challenging and time intensive. DESIGN: A quasi-experimental, one-group, pre,
      post, 6-week postintervention repeated measures study was conducted among inner
      city pregnant adolescents. METHOD: Study participants' nutrition knowledge,
      eating habits, and personal self-efficacy were measured prior to pregnant
      adolescents' participation in the workshop, immediately after the intervention
      and 6-weeks following the intervention. A total of four workshops were conducted
      over 14 months from 2014-2015. RESULTS: Gatekeepers were influential in
      recruitment efforts due to trusting relationship they had with study
      participants. The use of texting reminders and pregnant adolescent-related
      incentives that included gift bags and baby items were also effective recruitment
      and retention strategies. Despite designing the recruitment strategies and using
      a developmentally tailored workshop, based on empirical evidence gleaned from
      pregnant adolescents that was modified to meet study participant's schedules, an
      adequate sample was unable to be recruited and retained for this study.
      CONCLUSION: High-quality research studies that generate reliable and accurate
      data are essential in meeting the developmental and healthcare needs of pregnant
      adolescents. A major barrier in developing evidence-based care practices to
      promote the health of these young mothers and their children involves recruiting
      and retaining them in research studies.

PMID- 30187540
TI  - Sweet syndrome in association with enterobiasis.

PMID- 30187538
TI  - Is there still a role for balloon aortic valvuloplasty in the TAVR era?

PMID- 30187539
TI  - Right axilloaxillary cannulation for surgical management of a giant ascending
      aortic aneurysm.

PMID- 30187541
TI  - Job satisfaction, job stress and nurses' turnover intentions: The moderating
      roles of on-the-job and off-the-job embeddedness.
AB  - AIM: Using an interactionist perspective to test on-the-job embeddedness and off
      the-job embeddedness as possible moderators for the predictive effects of job
      satisfaction and job stress on nurses' turnover intentions. BACKGROUND: As
      turnover worsens nurse shortages across the globe, researchers needs to find ways
      to work out and reduce nurses' turnover intentions. By exploring contributory
      factors, namely on-the-job and off-the-job embeddedness as two distinctive forms
      that both act as moderators, we add to the literature on effective nurse
      retention and highlight that incorporating off-the-job factors can provide a more
      realistic understanding of why people consider leaving their organization.
      DESIGN: Survey of 361 nurses of the United Kingdom's (UK's) National Health
      Service, in 2016. METHOD: We conducted hierarchical multiple regression and
      simple slope analyses. RESULTS: Job satisfaction was negatively associated with
      turnover intentions, and this negative relationship was stronger when off-the-job
      embeddedness was high (vs. low). Job stress was positively related to turnover
      intentions, yet high (vs. low) off-the-job embeddedness buffered this
      relationship. In contrast, when on-the-job embeddedness was high (vs. low), the
      relationship between job stress and turnover intentions were even stronger.
      CONCLUSION: Results showed that using an interactionist perspective is useful in
      predicting nurse turnover. Nursing management should be made aware of the
      importance of being embedded off-the-job to prevent nurse turnover. This paper
      issues guidelines to form a more comprehensive staff retention programme for the
      healthcare sector.

PMID- 30187542
TI  - Patients' experiences 1-6 months after atrial fibrillation ablation: An holistic
      perspective.
AB  - AIM: To describe patients' experiences from a holistic perspective 1-6 months
      after atrial fibrillation (AF) ablation. BACKGROUND: Catheter ablation (CA) is an
      invasive treatment for AF. While CA has Class 1A indication, the latest
      guidelines for AF management state there is an urgent need to better understand
      complications in clinical practice to improve the quality of AF ablation
      procedures. DESIGN: A qualitative analytic approach based on a deductive and
      descriptive design was used. METHODS: Interviews of 19 patients, carried out from
      September 2016 to February 2017, were analysed using qualitative content
      analysis. FINDINGS: Five themes were identified; one in each life dimension due
      to the deductive design based on a holistic model: (a) having unexpected
      complications with a slower recovery; (b) discovering one's own self-management
      strategies when lacking information and insufficient follow-up; (c) managing
      resentment through different coping strategies while emotional reactions depended
      on feeling better or worse; (d) failing to receive full understanding and support
      from close ones, with social consequences when the biophysical level did not
      return to normal; (e) gradually adopting new life perspectives with a hope for a
      better future, despite having unmet expectations and uncertainty, leading to
      discovering existential matters. CONCLUSION: Patients' post CA experiences could
      be understood in terms of a holistic model. Their feelings of uncertainty caused
      by a lack of medical follow-up led to emotional reactions, the magnitude of which
      depended on feeling-well or worse. Patients' need more information about possible
      complications, suggesting follow-up and patient education needs improvement.

PMID- 30187543
TI  - Novel-graded traumatic brain injury model in rats induced by closed head impacts.
AB  - Traumatic brain injury (TBI) is a leading cause of death and disability
      worldwide. Due to the heterogeneity of human TBI, none of the available animal
      models can reproduce the entire spectrum of TBI. This study was designed to
      develop a novel-graded TBI rat model which is induced by closed head impacts
      (CHI) with reproducible brain damage and neurological dysfunction. A total of 75
      male Sprague-Dawley rats (200 +/- 20 g) were randomly equally divided into five
      groups: the Sham, 0.5, 0.6, 0.7 and 0.8 MPa groups. A custom-made, air-driven
      injury apparatus was used to induce CHIs (from 0.5 to 0.8 MPa). The kinematic
      parameters during the procedure were recorded by a force sensor and a high-speed
      camera. Mortality rate, duration of unconsciousness (latency period of righting
      reflex), modified neurological severity score (mNSS) and whole brain water
      content (BWC) were examined. Pathological changes were evaluated by hematoxylin
      eosin (HE) stain and immunohistochemical stain for amyloid precursor protein
      (APP). The impact force and speed were 785.3 +/- 14.12 N and 5.71 m/s in the 0.5
      MPa group, 837.72 +/- 10.41 N and 6.06 m/s in the 0.6 MPa group, 857.65 +/- 11.11
      N and 6.25 m/s in the 0.7 MPa group, and 955.6 +/- 16.35 N and 6.67 m/s in the
      0.8 MPa group. The periods of loss of righting reflex in 0.6-0.8 MPa groups were
      significantly higher than that in the Sham group. The mNSS score and BWC of the
      0.8 MPa group remained higher 24 h after injury than other groups. Brain damage
      was indicated by increased APP expression in TBI rats. In conclusion, the newly
      developed CHI rat model was a highly controlled and reproducible graded TBI
      model, and provided a useful tool to investigate the underlying mechanism and
      therapeutic effects of TBI with various injury severities.

PMID- 30187545
TI  - Selectively targeting the gut in inflammatory bowel disease: Targeting integrins.

PMID- 30187544
TI  - What is in our treasure chest? Australian pharmaceutical benefits scheme
      availability and criteria for prescribing biologics.

PMID- 30187546
TI  - Positioning biologics-A case-based discussion: Surgery and clinical trials.

PMID- 30187547
TI  - Swiss cheese tragedy case study.

PMID- 30187548
TI  - Making sense of clinical predictors.

PMID- 30187549
TI  - Debate session: So what causes inflammatory bowel disease? It's all in the genes.

PMID- 30187550
TI  - Selectively targeting the gut in inflammatory bowel disease: Session four
      summary.

PMID- 30187551
TI  - Positioning biologics-A case-based discussion: Ustekinumab.

PMID- 30187553
TI  - On the threshold of personalized medicine in inflammatory bowel disease: Next
      generation genetic predictors.

PMID- 30187552
TI  - Preventable disasters in inflammatory bowel disease-How we can help our patients
      and each other: Session five summary.

PMID- 30187554
TI  - Inflammatory bowel disease environmental risk factors versus genetics based on
      migration epidemiological studies.

PMID- 30187555
TI  - Positioning biologics-A case-based discussion: Vedolizumab.

PMID- 30187556
TI  - Real-world evidence for vedolizumab: Understanding the landscape.

PMID- 30187557
TI  - Predictors in inflammatory bowel disease: Looking into the magic ball: Session
      one summary.

PMID- 30187558
TI  - Update on the epidemiology of Australian inflammatory bowel disease from the
      Geelong cohort: Does diet matter after all?

PMID- 30187559
TI  - What can Australian Inflammatory Bowel Disease Association achieve in the next 3
      to 5 years?

PMID- 30187560
TI  - Positioning biological agents: Session two summary.

PMID- 30187561
TI  - Positioning biologics-A case-based discussion: Anti-tumor necrosis factor
      biological agents/biosimilars.

PMID- 30187562
TI  - Bugs and drugs: Predicting response to therapy.

PMID- 30187563
TI  - Personalizing inflammatory bowel disease treatment symposium: Foreward.

PMID- 30187564
TI  - Epidemiology of inflammatory bowel disease-nature versus nurture: Genes versus
      environment: Session three summary.

PMID- 30187565
TI  - Crohn's and Colitis Australia Inflammatory Bowel Disease Audit: Identifying
      disaster in waiting.

PMID- 30187566
TI  - Risk stratifying in real life.

PMID- 30187567
TI  - Debate session: So what causes inflammatory bowel disease? It's all in the
      environment.

PMID- 30187568
TI  - Abstracts of the 52nd Scientific Conference of the German speaking Mycological
      Society (DMykG) e. V. together with the Austrian Society for Medical Mycology
      (OGMM), 6 September - 8 September 2018, Innsbruck, Austria.

PMID- 30187569
TI  - Improvement of LVEF in patients with HFrEF with coronary heart disease after
      revascularization-A real-world study.
AB  - OBJECTIVE: This study aimed to explore the predictive factors for left
      ventricular ejection fraction (LVEF) improvement after revascularization.
      METHODS: This real-world study examined 993 patients with ischemic HFrEF who had
      received revascularization (PCI or CABG), had survived at least 90 days and had
      undergone an echocardiography review. Based on the change in the LVEF, we divided
      the patients into two groups. RESULT: We obtained 454 patients with >=10%
      improvement and 539 with <10% improvement or deterioration. By Cox regression
      analysis, we obtained five independent factors for LVEF improvement, including
      female (P = 0.018, OR 0.726, 95% CI 0.557-0.947), prior MI (P = 0.000, OR 0.590,
      95% CI 0.476-0.732), LVEF (P = 0.008, OR 0.967, 95% CI 0.943-0.991), digoxin (P =
      0.027, OR 0.708, 95% CI 0.521-0.961), loop diuretic (P = 0.000, OR 1.515, 95% CI
      1.208-1.901), and triple-vessel disease (P = 0.000, OR 1.462, 95% CI 1.192
      1.792). By multivariate generalized estimation, we obtained seven factors
      associated with the degree of improvement, namely, low LVEF, short LVESD, short
      LVEDD, no prior MI, no hyperuricemia, clopidogrel use and triple-vessel disease.
      CONCLUSIONS: The method of revascularization (PCI vs CABG) had no effect on LVEF
      improvement. Patients with severely impaired baseline LVEFs, triple-vessel
      disease, or no history of MI tended to exhibit marked LVEF improvement (>=10%)
      after revascularization. In addition, LVESD, LVEDD, hyperuricemia, clopidogrel
      use and loop diuretic affected the degree of improvement.

PMID- 30187570
TI  - Xanthomatous meningioma: A metaplastic or degenerative phenomenon?
AB  - Xanthomatous changes can be observed in various conditions including primary
      xanthomatosis that is linked to an underlying hypercholesterolemia and more
      commonly associated with secondary xanthomatous degenerative processes in
      neoplasm and chronic inflammation. Meningioma with extensive xanthomatous change
      is exceedingly rare. The presence of cholesterol clefts within this peculiar
      meningioma subtype has not been described. Herein, we report an unusual case of
      xanthomatous meningioma in an 83-year-old normolipidemic woman, who presented to
      us with worsening lower limb weakness and global aphasia. There was increasing
      evidence to suggest that the presence of xanthomatous changes in long-standing
      meningioma is merely a sequela of cellular degeneration rather than true
      metaplastic change as previously hypothesized. Hence, the diagnosis of
      "xanthomatous meningioma" in the metaplastic category should be revisited and
      considered as a distinct histological subtype. The possible histogenesis of such
      intriguing phenomenon is discussed with a review of the literature.

PMID- 30187571
TI  - Serum ferritin is not a reliable predictor to determine iron overload in
      thalassemia major patients post-hematopoietic stem cell transplantation.
AB  - OBJECTIVE: Iron overload (IO) in transfusion-dependent anemia persists after
      hematopoietic stem cell transplantation (HSCT) and can cause long-term organ
      damage. In many studies, the diagnosis of IO before and after HSCT is based on
      serum ferritin (SF) levels rather than on assessment of liver iron concentration
      (LIC) by MRI or SQUID. METHOD: In a retrospective multicenter study, we analyzed
      the concordance for indication of iron depletion therapy and correlation between
      LIC and SF of 36 thalassemia patients after HSCT. LIC was determined either by
      MRI-R2 (FerriScan(r)) or SQUID. RESULTS: The concordance between LIC and SF
      varies over time after transplant (P = 0.011). The correlation between SF and LIC
      was strong in the first year (Spearman's rho 0.75; P < 0.001). In agreement, the
      concordance between SF and LIC concerning indication for treatment was close to 1
      with an overall error rate ca. of 10%. In particular in the first year after
      HSCT, SF underestimates the degree of iron overload. However, in the longitudinal
      analysis since the second year post-HSCT onward no association was found between
      LIC and SF (P = 0.217). Furthermore, in the second year after HSCT, the overall
      error rate was 35%, whereas in the 3rd, 4th, and >4th year, it was 58%, 60%, and
      25%, respectively. CONCLUSIONS: Our data suggest serum ferritin is not a reliable
      predictor to determine iron overload in thalassemia patients after HSCT.

PMID- 30187572
TI  - Inhibitory effect of lidocaine on colonic spasm during colonoscopy: A multicenter
      double-blind, randomized controlled trial.
AB  - OBJECTIVES: Colonic spasm can interfere with colonoscopy, but antispasmodic
      agents can cause complications. This study aimed to assess the inhibitory effect
      of topical lidocaine compared with a placebo control. METHODS: In five tertiary
      care hospitals in Japan, 128 patients requiring endoscopic resection of a
      colorectal lesion were enrolled and randomly and double-blindly allocated to
      colonoscopy with topical administration of 2% lidocaine solution 20mL (LID, n =
      64) or normal saline 20mL (control, n = 64). During colonoscopy, the assigned
      solution was applied with a spray catheter near the lesion and the area was
      observed for three minutes. primary endpoint was the inhibitory effect at three
      time-points (1, 2 and 3 minutes after dispersion), using a three-point scale
      (excellent, fair, poor). Secondary endpoints were rebound spasm and adverse
      events. All endpoints were scored in real time. Serum lidocaine levels were
      measured in 32 patients (LID 16, control 16). RESULTS: There were no significant
      differences between groups in patient demographics. At all time-points, the
      proportion of patients with "excellent" scores was greater in LID group than
      control group, with significant differences observed at 2 minutes (p = 0.02) and
      3 minutes (p = 0.02). In LID group, the rate of "excellent" scores increased by
      12.5% at 2 minutes and was maintained at 3 minutes. Rebound spasm did not occur
      in LID group, compared with 15.6% of control group (p = 0.001). There were no
      adverse events in LID group. All serum lidocaine levels were below detectable
      levels. CONCLUSIONS: Topical lidocaine is an effective and safe method for
      suppressing colorectal spasm during colonoscopy (UMIN000024733).

PMID- 30187573
TI  - Getting through career crises: Insights from history, philosophy and research.

PMID- 30187574
TI  - Using trajectory models to assess the effect of hydrocodone upscheduling among
      chronic hydrocodone users.
AB  - PURPOSE: In October 2014, the US Drug Enforcement Agency moved hydrocodone
      combination products (HCPs) from schedule III to II of the Controlled Substances
      Act, further restricting their access. The aim of the study is to quantify the
      effect of hydrocodone's "upscheduling" on the use of opioid and nonopioid
      analgesics among chronic users. METHODS: Using IQVIA LRx LifeLink anonymized
      pharmacy data 2013 to 2015, we performed interrupted time series analysis and
      group-based trajectory modeling to characterize the effect of rescheduling on 316
      731 long-term hydrocodone users. Main measures were the number of prescriptions,
      patients, tablets, and morphine milligram equivalents of opioids and nonopioid
      analgesics pre and post the policy change. We used logistic regression to assess
      the relationship between sociodemographic characteristics and these measures.
      RESULTS: The schedule change was associated with significant declines in opioid
      prescriptions (20.9%, from 421 798 to 333 627) and the number of patients using
      opioids (11.4%, from 307 974 to 272 804). Majority of hydrocodone users filled
      prescriptions for nonopioid analgesics with some declines in the number of users
      after the schedule change (5.2%, from 181 085 to 171 758). Based on group-based
      trajectory models, majority of patients continued to fill HCP prescriptions
      consistently after the policy change, while 15.4% showed large declines in HCP
      use, accounting for two-thirds of the decrease in opioid volume. There was no
      evidence that the policy change was associated with significant increases in the
      use of alternative analgesics. CONCLUSIONS: The upscheduling of hydrocodone led
      to reductions in opioid use, which were concentrated among a small subset of
      chronic hydrocodone users, without evidence of commensurate increases in the use
      of alternative pharmacologic pain treatments.

PMID- 30187575
TI  - Multimodal skin lesion classification using deep learning.
AB  - While convolutional neural networks (CNNs) have successfully been applied for
      skin lesion classification, previous studies have generally considered only a
      single clinical/macroscopic image and output a binary decision. In this work, we
      have presented a method which combines multiple imaging modalities together with
      patient metadata to improve the performance of automated skin lesion diagnosis.
      We evaluated our method on a binary classification task for comparison with
      previous studies as well as a five class classification task representative of a
      real-world clinical scenario. We showed that our multimodal classifier
      outperforms a baseline classifier that only uses a single macroscopic image in
      both binary melanoma detection (AUC 0.866 vs 0.784) and in multiclass
      classification (mAP 0.729 vs 0.598). In addition, we have quantitatively showed
      the automated diagnosis of skin lesions using dermatoscopic images obtains a
      higher performance when compared to using macroscopic images. We performed
      experiments on a new data set of 2917 cases where each case contains a
      dermatoscopic image, macroscopic image and patient metadata.

PMID- 30187576
TI  - Family carers' experiences of participating in a weight management programme for
      overweight children and adolescents with intellectual disabilities: An
      exploratory study.
AB  - AIM: To gain insight into the experiences of family carers participating in a
      weight management programme via mHealth tools for overweight children and
      adolescents with intellectual disabilities. BACKGROUND: Many weight reduction
      programs fail to show positive and sustainable impacts due to not involving
      parents, who are usually unavailable to attend school-based health programs. The
      mHealth interactive interventions were carried out in September 2015-August 2016,
      engaging carers to monitor and sustain their children's healthy lifestyle
      behaviours at home being one way to achieve this. DESIGN: Qualitative research
      design to conduct focus group discussion with family carers involved in a school
      based weight management programme via the mHealth interventions. METHODS: An
      exploratory study was used to examine family carers' views of participating in a
      weight management programme. Focus group interviews examined the in-depth
      experiences of 20 family carers in providing social support and monitoring
      lifestyle behaviours via the mHealth interactive interventions. RESULTS: Twenty
      family carers were recruited and four themes emerged: (a) improving family carer
      child interactions and communications; (b) gaining useful and practical health
      information from experts; (c) supporting each other via an mHealth platform; and
      (d) appreciating the collaborative effort between school personnel and family
      carers. Family carers stressed the usefulness of the mHealth interactive
      interventions in monitoring and sustaining the children's healthy lifestyle
      behaviours at home. CONCLUSION: The mHealth interactive interventions for
      increasing family carers' involvement and monitoring were well received. The
      findings provide new insights into using mHealth interventions in future weight
      management programmes involving parental participation in the home environment.

PMID- 30187577
TI  - Left distal trans-radial access facilitates earlier discharge post-coronary
      angiography.
AB  - AIMS: In 2017, Kiemeneij published a paper on distal trans-radial artery access
      for coronary angiography in 62 patients. This paper proposed several advantages
      to this method. Since this paper was published, several other papers have been
      published describing this technique, with less than 200 cases in total described.
      We performed a non randomized control study of left distal trans-radial access in
      patients undergoing coronary angiography in our center. METHODS: We prospectively
      identified patients presenting for coronary angiography to our center for
      enrolment in this study. We recruited 94 patients (47 ldTRA, 47 age and sex
      matched controls). Pre-defined endpoints for the study were as follows: time
      until radial compression device (RCD) removal, procedural time, radiation dose,
      fluoroscopy time, and contrast dose. RESULTS: Patient and procedural
      characteristics did not differ significantly between the two groups. With regard
      to our primary endpoint, patients undergoing ldTRA required, on average, 69 min
      less time until removal of the RCD (167.8 +/- 30 vs 236.6 +/- 63.9 min, P <
      0.0001). Procedural length did not vary between groups (28.95 +/- 5.89 vs 29.76
      +/- 8.16 min, P = 0.5824). Similarly, there was no statistically significant
      difference in radiation dose area product (5032.66 +/- 2740 vs 4826 +/- 2796
      Gy/cm2 , P = 0.7191), contrast dose (82.93 +/- 23 vs 92.1 +/- 33 mL, P = 0.1215),
      and fluoroscopy time between the two groups (5.41 +/- 3.42 vs 4.82 +/- 2.97 min,
      P = 0.3742). CONCLUSIONS: Our study confirms that ldTRA is a feasible technique
      for diagnostic coronary angiography in a modern cardiac catheterization
      laboratory. It results in decreased post-procedure radial artery compression time
      without increasing procedural time or radiation dose.

PMID- 30187578
TI  - NKT cells - New players in CAR cell immunotherapy?
AB  - Low levels of peripheral blood natural killer T (NKT) cells in cancer patients
      and a favorable outcome associated with a high number of tumor-infiltrating NKT
      cells demonstrated in several studies indicated the important role of these
      immune cells in the antitumor response. With effective antitumor immunity via
      direct tumor lysis, cytokine modulation of effector cells and regulation of
      immunosuppressive cells, type I NKT cells display interesting features/properties
      for the rapidly developing chimeric antigen receptor (CAR) technology. Due to
      their restriction to the monomorphic HLA-like molecule CD1d, but not to the
      polymorphic human leukocyte antigen (HLA), NKT CAR cells show potential for
      enabling autologous and allogeneic/off-the-shelf cancer immunotherapy. Promising
      results were obtained in preclinical NKT CAR cell studies, but clinical trials
      have not yet been conducted. In this review, we summarize the biological features
      of NKT cells, their role in antitumor immunity and recent advances in the
      development of NKT CAR cells.

PMID- 30187579
TI  - A clarion call for preventing taxonomical errors of dermatophytes using the
      example of the novel Trichophyton mentagrophytes genotype VIII uniformly isolated
      in the Indian epidemic of superficial dermatophytosis.
AB  - An alarming pan Indian increase in the incidence of superficial dermatophytosis
      has been noticed over the past 5-6 years. Recent studies have demonstrated
      emerging predominance of Trichophyton (T.) mentagrophytes as the causative
      organism in such cases. Interestingly, a distinct Indian genotype of T.
      mentagrophytes has been identified and recognised with the help of sequencing of
      the ITS region of the rDNA. That has, however, led to a basic confusion owing to
      the newly introduced taxonomy of dermatophytes in 2017. According to this most
      recently suggested classification and new taxonomy of dermatophytes, the former
      "T. mentagrophytes complex" is differentiated into T. mentagrophytes (zoophilic
      strains) and T. interdigitale (anthropophilic strains). We have noticed that in
      some recent studies the causative agent of the chronic, relapsing dermatophytosis
      outbreak in India has been described as T. interdigitale. In our opinion, it is
      very likely that these T. interdigitale strains isolated in Delhi and Chennai in
      India are indeed strains more closely related to the neotype of T. mentagrophytes
      and not strains of T. interdigitale. We therefore want to underscore the
      importance of a common nomenclature of species in accordance with the new
      taxonomy of dermatophytes. This would most likely facilitate better understanding
      of the issue amongst dermatologists and microbiologists in general. Mistaken
      identification of Trichophyton isolates not limited to India is very likely to
      occur due to the lack of appropriate molecular diagnosis which in turn is based
      on the already published data that presumably wrongly identify one species
      instead of the other.

PMID- 30187580
TI  - Expanding the spectrum of pediatric NTRK-rearranged fibroblastic tumors to the
      central nervous system: A case report with RBPMS-NTRK3 fusion.
AB  - We report a case of a 20-month-old male presenting with seizures who was found to
      have a hyperintense lesion on T2-weighted images of magnetic resonance imaging in
      the left medial temporal lobe that was initially clinically and radiologically
      thought to be either low-grade glioma or focal cortical dysplasia. Histologic,
      immunohistochemical and molecular evaluation (array comparative genomic
      hybridization, Archer fusion panel) of the resection specimen demonstrated a
      highly infiltrative fibroblastic spindle cell neoplasm with mild nuclear atypia
      and an RBPMS-NTRK3 fusion. NTRK-fused mesenchymal tumors are known to involve
      extracranial sites but, to our knowledge, have not been described within the
      central nervous system. Accurate and timely diagnosis of this entity has
      important prognostic and therapeutic implications, as NTRK-fused tumors may recur
      locally and may respond to selective kinase inhibitor therapies.

PMID- 30187581
TI  - Acquired cystic disease-associated renal cell carcinoma is the most common
      subtype in long-term dialyzed patients: Central pathology results according to
      the 2016 WHO classification in a multi-institutional study.
AB  - New pathological subtypes of renal cell carcinoma (RCC) were designated in the
      2016 World Health Organization (WHO) classification corresponding to the features
      commonly seen in patients with end-stage renal disease (ESRD). To determine the
      clinicopathological findings of new subtypes, we reanalyzed all sections from 315
      kidneys in 291 ESRD patients bearing RCC tumors surgically resected in three
      Japanese institutes by the central pathologist. Clear cell RCC was diagnosed in
      144 kidneys (45.7%), acquired cystic disease (ACD)-associated RCC in 100 (31.7%),
      papillary RCC in 41 (13.0%), and other minor subtypes in 30 (9.52%). Multivariate
      analysis showed that longer duration of dialysis, young age, and male sex were
      independent prognostic clinical factors for the occurrence of ACD-associated RCC.
      ACD-associated RCC included more WHO/International Society of Urologic Pathology
      (ISUP) grade 3/4 cases compared to other RCCs. In contrast, other unfavorable
      findings were less frequent in ACD-associated RCC, including the presence of a
      sarcomatoid component, lymphovascular invasion, and necrosis. In conclusion, ACD
      associated RCC is a common histology in Japanese patients with ESRD. In addition,
      ACD-associated RCC showed more cases with a higher WHO/ISUP grade, but fewer
      cases with other unfavorable pathological features, suggesting a favorable
      prognosis of ACD-associated RCC.

PMID- 30187582
TI  - Household coping strategies after an adult noncommunicable disease death in
      Bangladesh.
AB  - When facing adverse health from noncommunicable disease (NCD), households adopt
      coping strategies that may further enforce poverty traps. This study looks at
      coping after an adult NCD death in rural Bangladesh. Compared with similar
      households without NCD deaths, households with NCD deaths were more likely to
      reduce basic expenditure and to have decreased social safety net transfers.
      Household composition changes showed that there was demographic coping for prime
      age deaths through the addition of more women. The evidence for coping responses
      from NCDs in low- and middle-income countries may inform policy options such as
      social protection to address health-related impoverishment.

PMID- 30187583
TI  - Intra-ovarian dynamic blood flow in pseudopregnant rabbits during prostaglandin
      F2alpha-induced luteolysis.
AB  - In the present study, we evaluated the dynamic changes of intra-ovarian blood
      flow, by real-time colour-coded and pulsed Doppler ultrasonography, as well as
      the immunopresence of prostaglandin F2alpha (PGF2alpha) receptor (FP) and
      peripheral plasma progesterone concentrations in pseudopregnant rabbit after
      PGF2alpha treatments at either early- (4 days) and mid-luteal (9 days) stages.
      During the pre-treatment observation interval of one hour, the ovarian blood
      flows showed a fluctuating pattern. Independently of luteal stage, PGF2alpha
      administration caused a fourfold decline in the blood flow within 40 min that was
      followed 50 min later by a reactive hyperaemia that lasted several hours, while
      the resistive index showed an opposite trend. Twenty-four hour later, the blood
      flow was one half that measured before PGF2alpha injection. At day 4 of
      pseudopregnancy, PGF2alpha did not affect peripheral plasma progesterone
      concentrations, but at day 9, it caused functional luteolysis as progesterone
      levels declined 6 hr later to reach basal values after 24 hr. The changes in the
      ovarian blood flows of pseudopregnant rabbits receiving PGF2alpha were
      accompanied by simultaneous changes in the resistance index. This biphasic
      response in the blood flow and vascular resistances likely reflects reactive
      hyperaemia following vasoconstriction. By immunohistochemistry, strong positive
      immune reaction for FP was detected in the cytoplasm of endothelial cells of
      ovarian arteries, veins and capillaries. In conclusion, these results suggest
      that PGF2alpha could acutely regulate the ovarian blood flow of pseudopregnant
      rabbits, even if there is no evidence of a blood flow reduction anticipating
      luteolysis.

PMID- 30187584
TI  - A spatially explicit hierarchical model to characterize population viability.
AB  - Many of the processes that govern the viability of animal populations vary
      spatially, yet population viability analyses (PVAs) that account explicitly for
      spatial variation are rare. We develop a PVA model that incorporates
      autocorrelation into the analysis of local demographic information to produce
      spatially explicit estimates of demography and viability at relatively fine
      spatial scales across a large spatial extent. We use a hierarchical, spatial,
      autoregressive model for capture-recapture data from multiple locations to obtain
      spatially explicit estimates of adult survival (phiad ), juvenile survival
      (phijuv ), and juvenile-to-adult transition rates (psi), and a spatial
      autoregressive model for recruitment data from multiple locations to obtain
      spatially explicit estimates of recruitment (R). We combine local estimates of
      demographic rates in stage-structured population models to estimate the rate of
      population change (lambda), then use estimates of lambda (and its uncertainty) to
      forecast changes in local abundance and produce spatially explicit estimates of
      viability (probability of extirpation, Pex ). We apply the model to demographic
      data for the Sonoran desert tortoise (Gopherus morafkai) collected across its
      geographic range in Arizona. There was modest spatial variation in lambda^ (0.94
      1.03), which reflected spatial variation in phi^ad (0.85-0.95), phi^juv (0.70
      0.89), and psi^ (0.07-0.13). Recruitment data were too sparse for spatially
      explicit estimates; therefore, we used a range-wide estimate ( R^  = 0.32 1-yr
      old females per female per year). Spatial patterns in demographic rates were
      complex, but phi^ad , phi^juv , and lambda^ tended to be lower and psi^ higher in
      the northwestern portion of the range. Spatial patterns in Pex varied with local
      abundance. For local abundances >500, Pex was near zero (<0.05) across most of
      the range after 100 yr; as abundances decreased, however, Pex approached one in
      the northwestern portion of the range and remained low elsewhere. When local
      abundances were <50, western and southern populations were vulnerable (Pex  >
      0.25). This approach to PVA offers the potential to reveal spatial patterns in
      demography and viability that can inform conservation and management at multiple
      spatial scales, provide insight into scale-related investigations in population
      ecology, and improve basic ecological knowledge of landscape-level phenomena.

PMID- 30187585
TI  - Genomic targeting by recombinase-mediated cassette exchange in the spotted wing
      drosophila, Drosophila suzukii.
AB  - Drosophila suzukii is a significant pest of stone and small fruits. The genome of
      this species has been sequenced and manipulated by transposon-mediated
      transformation and CRISPR/Cas9 gene editing. These technologies open a variety of
      possibilities for functional genomics and genetic modifications that might
      improve biologically based population control strategies. Both of these
      approaches, however, would benefit from genome targeting that would avoid
      position effects and insertional mutations associated with random transposon
      vector insertions, and the limited DNA fragment insertion size allowed by gene
      editing. Here, we describe an efficient recombinase-mediated cassette exchange
      (RMCE) system for D. suzukii in which heterospecific lox recombination sites were
      integrated into the genome by transposon-mediated transformation and subsequently
      targeted for double recombination by a donor vector in the presence of Cre
      recombinase. Three loxN/lox2272 landing site lines have previously been created
      in D. suzukii, and quantitative PCR determined that polyubiquitin-regulated
      enhanced green fluorescent protein expression is least susceptible to position
      effect suppression in the 443_M26m1 line. We presume that RMCE target sites may
      also be inserted more specifically into the genome by homology-directed repair
      gene editing, thereby avoiding position effects and mutations, while eliminating
      restrictions on the size of donor constructs for subsequent insertion.

PMID- 30187586
TI  - Identification and biofilm development by a new fungal keratitis aetiologic
      agent.
AB  - BACKGROUND: In recent years, human keratitis caused by fungal plant pathogens has
      become more common. Biofilm is a structure that confers adaptations and virulence
      to fungi in keratitis. Neoscytalidium spp. are phytopathogenic and recently have
      been recognised as a human pathogen, using biofilm formation as a virulence
      factor. OBJECTIVES: The aim of this study was isolation, identification (at the
      species level) and characterisation of a new fungal keratitis agent.
      PATIENTS/METHODS: The fungus was isolated from a 67-year-old male patient with a
      corneal ulcer. Biofilm formation and structure were evaluated by colorimetric
      methods and microscopy. To identify the fungus, morphological characteristics
      were examined and a phylogenetic analysis was performed. RESULTS AND CONCLUSIONS:
      We report the identification of a fungus, a member of the genus Neoscytalidium
      which is associated with human keratitis. Phylogenetic analysis and morphological
      observations on conidiogenous cells, which occur only in arthric chains in aerial
      mycelium and the coelomycetous synasexual morph is absent, identified a new
      species, Neoscytalidium oculus sp. nov. The fungus formed biofilm at a
      concentration of 1 * 106  conidia/mL, during 96 hours of incubation at 37 degrees
      C, and also manifested haemolysis and melanin production. This is the first
      report in Latin America of a new species of Neoscytalidium from a clinical
      isolate has been identified.

PMID- 30187587
TI  - Suppression of influenza B virus replication by sakuranetin and mode of its
      action.
AB  - This study aimed to investigate in vitro the anti-influenza B/Lee/40 virus effect
      of sakuranetin and mode of its action. The sakuranetin exhibited potent antiviral
      activity against influenza B/Lee/40 virus, reducing the formation of a visible
      cytopathic effect, with a 50% inhibitory concentration (IC50 ) of 7.21 MUg/ml and
      no cytotoxicity at a concentration of 100 MUg/ml, and the derived therapeutic
      index (TI) was >13.87. Oseltamivir showed weak anti-influenza B/Lee/40 virus
      activity with IC50 of 80.74 MUg/ml, 50% cytotoxicity concentration of >100
      MUg/ml, and TI of >1.24. Sakuranetin also showed effective inhibitory effects
      when added at the viral attachment, entry, and postentry steps. Moreover,
      sakuranetin effectively inactivated influenza B/Lee/40 virus infection in dose-
      and temperature-dependent manners. Sakuranetin indicated an inhibitory effect in
      viral RNA synthesis in the presence of 100 MUg/ml of sakuranetin. Overall, this
      research revealed that sakuranetin could inhibit influenza B/Lee/40 virus
      replication and that sakuranetin may be involved in the virus attachment, entry,
      and postentry. Therefore, sakuranetin is a good candidate for a chemopreventive
      agent for influenza virus-related diseases.

PMID- 30187589
TI  - Royal College of Surgeons Edinburgh Surgical Anatomy Workshops (Wade Programme)
      Promote Student Knowledge and Interest in Anatomy and Surgery.

PMID- 30187590
TI  - Factors distinguishing important identified risks from important potential risks
      in orphan and nonorphan drugs: An analysis of safety specifications of Japan and
      European Union risk management plans.
AB  - PURPOSE: The purposes of the study are to compare safety specifications between
      Japan and the European Union (EU) and to identify the factors affecting
      categorization of important identified or potential risks. METHODS: Safety
      specifications were collected from orphan and nonorphan drugs approved in Japan
      between 2014 and 2016, and in the EU as of October 2017. Outcome was defined
      dichotomously as listed as important identified risks or potential risks. A mixed
      effects logistic regression was performed to estimate odds ratios of being listed
      as important identified risks. RESULTS: This study included 20 orphan and 33
      nonorphan drugs. The number of safety specifications per drug and the
      distribution of risk categories were significantly different between Japan and
      the EU regardless of orphan status. In orphan drugs, the occurrence of serious
      adverse events (AEs) during clinical trials for new drug applications was
      associated with a higher probability of being listed as important identified
      risks in Japan, while AE rate (%) was positively associated with being listed as
      important identified risks in the EU. For nonorphan drugs in Japan, AE occurring
      at a high rate, adverse drug reactions (ADRs) listed as important identified
      risks in EU risk management plans, and clinically significant ADRs known in
      similar drugs were likely to be listed as important identified risks, whereas a
      >=1.4 risk ratio was associated with a higher probability of being listed as
      important identified risks in the EU. CONCLUSIONS: Factors affecting risk
      categories were different between Japan and the EU, which might contribute to the
      difference in safety specifications between these 2 regions.

PMID- 30187588
TI  - A comprehensive analysis of the allergenicity and IgE epitopes of myosinogen
      allergens in Scylla paramamosain.
AB  - BACKGROUND: Scylla paramamosain is one of the most common and serious food
      allergens in Asia. Therefore, research on its prevalence, accurate diagnosis, and
      IgE-binding pattern of the allergens is crucial. OBJECTIVE: To identify the IgE
      epitopes of the myosinogen allergens in S. paramamosain using phage peptide
      library. METHODS: The prevalence of allergy to crabs (AC) and of sensitization
      was analysed using a questionnaire and a serological assay. BAT was performed by
      flow cytometry, and its diagnostic performance was evaluated in relation to
      allergens purified from crab myosinogen. IgE-binding epitopes were identified by
      phage display using the IgE from patients with AC. Sequence- and structure-based
      bioinformatics analyses were performed to identify allergenic epitopes. RESULTS:
      Crab was the most common cause of food allergies in this study. Subjects with AC
      (n = 30) with clear clinical symptoms were identified by immunoblotting and BAT.
      All of the myosinogen allergens triggered basophil activation; surface expression
      of CD63 and CD203c was higher in patients allergic to AK and FLN c than in
      patients allergic to SCP and TIM. In addition to six conformational epitopes of
      SCP, six linear epitopes and eight conformational epitopes of AK were identified.
      Five linear epitopes and three conformational epitopes of TIM, nine linear and
      ten conformational epitopes of FLN c were also identified, and the sequence
      VH(I/T) L was appeared in epitopes of both TIM and FLN c. The number of epitopes
      showed consistency with the value of BAT. CONCLUSIONS AND CLINICAL RELEVANCE: BAT
      can be used for accurate diagnosis of AC. Identification of particular allergenic
      motifs could be a valuable tool for prevention, diagnosis, and treatment of food
      allergies.

PMID- 30187591
TI  - Zwitterionic Design Principle of Nickel(II) Catalysts for Carbonylative
      Polymerization of Cyclic Ethers.
AB  - Zwitterionic structure is necessary for NiII complexes to catalyze carbonylative
      polymerization (COP) of cyclic ethers. The cationic charge at the NiII center
      imparts sufficient electrophilicity to the Ni-acyl bond for it to react with
      cyclic ethers to give an acyl-cyclic ether oxonium intermediate, while the ligand
      centered anionic charge ensures that the resultant oxonium cation is ion-paired
      with the Ni0 nucleophile. The current catalysts give non-alternating copolymers
      of carbon monoxide and cyclic ethers and are the most effective when both
      ethylene oxide and tetrahydrofuran are present as the cyclic ether monomers.

PMID- 30187592
TI  - Adverse effects of fillers.
AB  - Filler injections belong to the most frequently performed noninvasive beautifying
      procedures. When done correctly they are generally well tolerated. However, a
      number of factors, such as poor filler quality, and particularly host as well as
      user dependent filler reactions may lead to unwanted effects. These may be early,
      late, or delayed events with characteristics for each of them. Temporary fillers
      almost invariably cause temporary side effects whereas those of permanent fillers
      may last forever. Some fillers are notorious for their poor safety profile; for
      example, silicone is banned in the European Union and the United States but
      nevertheless used by many practitioners and beauticians. Many fillers can be
      identified in histopathologic sections allowing specific measures to be
      instituted.

PMID- 30187593
TI  - Effects of a federal housing voucher experiment on adolescent binge drinking: a
      secondary analysis of a randomized controlled trial.
AB  - AIMS: To test how a housing voucher generating residential mobility to lower
      poverty neighborhoods, compared with public housing controls, influenced
      adolescent binge drinking, and whether gender modified effects. DESIGN: A multi
      site household-level three-arm randomized trial of a housing intervention
      executed 1994-98, evaluated 2001-02. SETTING: Five US cities: Baltimore, MD;
      Boston, MA; Chicago, IL; Los Angeles, CA; and New York, NY. PARTICIPANTS: A total
      of 3537 adolescents in 4248 low-income eligible families were randomized; 2829
      adolescents were analyzed at the interim evaluation (1950 in treatment; 879 in
      the control group). Attrition bias was accounted for with a 3-in-10 oversampling
      of hard-to-reach participants (effective response rate: 89%). INTERVENTIONS: The
      Moving to Opportunity (MTO) trial randomized volunteer low-income families in
      public housing to receive (1) rental subsidies redeemable in neighborhoods with <
      10% tract poverty plus housing counseling, (2) unrestricted Section 8 rental
      subsidies or (3) to remain in public housing. We pooled the subsidy ('treatment')
      groups because they were conceptually similar and there was no evidence of
      statistical differences between groups on binge drinking. MEASUREMENTS: Primary
      outcome: past month binge drinking (five or more drinks in one sitting).
      FINDINGS: Adolescent binge drinking prevalence was 3.9% for treatment and 3.2%
      for control. The intention-to-treat (ITT) main effect of subsidy treatment
      (versus control) on binge drinking was non-significant, but treatment effects
      were different for girls and boys (treatment-gender interaction P = 0.002). MTO
      treatment reduced girls' binge drinking [odds ratio (OR) = 0.48, 95% confidence
      interval (CI) = 0.24-0.96, P = 0.037], but increased boys' binge drinking (OR =
      2.37, 95% CI = 1.13-4.97, P = 0.023), compared with controls. Results were
      similar for secondary alcohol outcomes. Instrumental variable (IV) results
      adjusting for treatment compliance were comparable with ITT, but larger.
      CONCLUSIONS: A housing subsidy treatment that enables low-income families to move
      from public to private housing appears to lessen girls' binge drinking but
      increases boys' binge drinking, compared with controls.

PMID- 30187595
TI  - Usefulness of 3-D computed tomography for diagnosis of abusive head trauma.

PMID- 30187594
TI  - Cap-ScoreTM prospectively predicts probability of pregnancy.
AB  - Semen analysis (SA) poorly predicts male fertility, because it does not assess
      sperm fertilizing ability. The percentage of capacitated sperm determined by GM1
      localization ("Cap-ScoreTM"), differs between cohorts of fertile and potentially
      infertile men, and retrospectively, between men conceiving or failing to conceive
      by intrauterine insemination (IUI). Here, we prospectively tested whether Cap
      Score can predict male fertility with the outcome being clinical pregnancy within
      <=3 IUI cycles. Cap-Score and SA were performed (n = 208) with outcomes initially
      available for 91 men. Men were predicted to have either low (n = 47) or high (n =
      44) chance of generating pregnancy using previously-defined Cap-Score reference
      ranges. Absolute and cumulative pregnancy rates were reduced in men predicted to
      have low pregnancy rates versus high ([absolute: 10.6% vs. 29.5%; p = 0.04];
      [cumulative: 4.3% vs. 18.2%, 9.9% vs. 29.1%, and 14.0% vs. 32.8% for cycles 1-3;
      n = 91, 64, and 41; p = 0.02]). Only Cap-Score, not male/female age or SA
      results, differed significantly between outcome groups. Logistic regression
      evaluated Cap-Score and SA results relative to the probability of generating
      pregnancy (PGP) for men who were successful in, or completed, three IUI cycles (n
      = 57). Cap-Score was significantly related to PGP (p = 0.01). The model fit was
      then tested with 67 additional patients (n = 124; five clinics); the equation
      changed minimally, but fit improved (p < 0.001; margin of error: 4%). The Akaike
      Information Criterion found the best model used Cap-Score as the only predictor.
      These data show that Cap-Score provides a practical, predictive assessment of
      male fertility, with applications in assisted reproduction and treatment of male
      infertility.

PMID- 30187596
TI  - Photoluminescence Enhancement of Carbon Dots by Surfactants at Room Temperature.
AB  - During the past decade, increasing attention has been paid to fluorescent carbon
      dots (CDs) due to their unique photoluminescence (PL) properties. As synthetic
      methods gradually develop, many post-functionalization strategies have been
      developed to enhance the PL of CDs. However, in most cases, the PL enhancement
      was less than 10-fold with multistep modification processes. In this work, a
      facile and efficient post-functionalization strategy was successfully applied to
      enhance the PL intensity of CDs dramatically up to 69 times by surfactants at
      room temperature for the first time. Furthermore, the mechanism of surfactant
      induced PL enhancement of CDs was investigated and in vivo bioimaging was
      performed. The results demonstrated that electrostatic/non-electrostatic
      interactions between CDs and surfactants could effectively lower the vibration
      and rotation of CDs, increase radiative decay processes and, thus, enhance the PL
      of CDs. This finding may provide new insights into the strategies for enhancing
      the PL of CDs, further broadening their potential applications.

PMID- 30187598
TI  - Site-Specific Deoxyfluorination of Small Peptides with [18 F]Fluoride.
AB  - Radiolabeled receptor-binding peptides are an important class of positron
      emission tomography tracers owing to achievable high binding affinities and their
      rapid blood clearance. Herein, a method to introduce a 4-[18 F]fluoro
      phenylalanine residue into peptide sequences is reported, by chemoselective radio
      deoxyfluorination of a tyrosine residue using a traceless activating group. The
      replacement of only one hydrogen atom with [18 F]fluoride results in minimal
      structural perturbation of the peptide, which is desirable in the labeling of
      tracer candidates.

PMID- 30187597
TI  - Anemia associated with increased hepcidin in two children with Castleman disease.

PMID- 30187599
TI  - Add-on peginterferon alfa-2a to nucleos(t)ide analogue therapy for Caucasian
      patients with hepatitis B 'e' antigen-negative chronic hepatitis B genotype D.
AB  - Nucleos(t)ide analogues (NAs) and peginterferon have complementary effects in
      chronic hepatitis B, but it is unclear whether combination therapy improves
      responses in genotype D-infected patients. We conducted an open-label study of
      peginterferon alfa-2a 180 MUg/week added to ongoing NA therapy in hepatitis B e
      antigen (HBeAg)-negative, genotype D-infected patients with HBV DNA <20 IU/mL.
      The primary endpoint was proportion of patients with >=50% decline in serum HBsAg
      by the end of the 48-week add-on phase. Seventy patients received treatment, 11
      were withdrawn at week 24 for no decrease in HBsAg, and 14 withdrew for other
      reasons. Response rate (per-protocol population) was 67.4% (29/43) at week 48
      (95% confidence interval [CI]: 51, 81) and 50.9% (28/55) at week 96 (95% CI: 38,
      66). Median serum HBsAg decreased throughout peginterferon alfa-2a treatment and
      was significantly lower than baseline at weeks 48, 72 and 96 (P<.001). Decreases
      in HBsAg of >=0.5-log10 and >=1-log10 were documented in 19 (44.2%) and 6 (14.0%)
      patients at week 48 and 6 (10.9%) and 17 (30.9%) patients at week 96. The
      proportion of patients with HBsAg <1000, <500, <100 and <10 IU/mL at >=1
      timepoint during treatment was 78.6% (n=44), 57.1% (n=32), 21.4% (n=12) and 7.1%
      (n=4). Interferon gamma-induced protein 10 increased from baseline up to week 48,
      with week 12 levels significantly associated with response at week 48. Addition
      of peginterferon alfa-2a to ongoing NA therapy significantly decreased HBsAg
      levels in HBeAg-negative patients with genotype D infection This article is
      protected by copyright. All rights reserved.

PMID- 30187600
TI  - Interreader agreement of PI-RADS v. 2 in assessing prostate cancer with
      multiparametric MRI: A study using whole-mount histology as the standard of
      reference.
AB  - BACKGROUND: Most studies assessing interreader agreement of Prostate Imaging
      Reporting and Data System v. 2 (PI-RADS v2) have used biopsy as the standard of
      reference, thus carrying the risk of not definitively noting all existent
      cancers. PURPOSE: To evaluate the interreader agreement in assessing prostate
      cancer (PCa) of PI-RADS v2, using whole-mount histology as the standard of
      reference. STUDY TYPE: Monocentric prospective cohort study. POPULATION: In all,
      48 patients with biopsy-proven PCa referred for radical prostatectomy, undergoing
      staging multiparametric magnetic resonance imaging (mpMRI) between May 2016 to
      February 2017. FIELD STRENGTH/SEQUENCE: 3.0T system using high-resolution T2 
      weighted imaging, diffusion-weighted imaging (echo-planar imaging with maximum b
      value 2000 sec/mm2 ), and dynamic contrast-enhanced imaging (T1 -weighted high
      resolution isotropic volume examination; THRIVE) ASSESSMENT: Three radiologists
      blinded to final histology (2-8 years of experience) analyzed mpMRI images
      independently, scoring imaging findings in accordance with PI-RADS v2. On a per
      lesion basis, we calculated overall and pairwise interreader agreement in
      assigning PI-RADS categories, as well as assessing malignancy with categories >=3
      or >=4, and stage >=pT3. STATISTICAL TESTS: Cohen's kappa analysis of agreement.
      RESULTS: On 71 lesions found on histology, there was moderate agreement in
      assigning PI-RADS categories to all cancers (k = 0.53) and clinically significant
      cancers (csPCa) (k = 0.47). Assessing csPCa with PI-RADS >=4 cutoff provided
      higher agreement than PI-RADS >=3 cutoff (k = 0.63 vs. 0.57). Interreader
      agreement was higher between more experienced readers, with the most experienced
      one achieving the highest cancer detection rate (0.73 for csPCa using category
      >=4). There was substantial agreement in assessing stage >=pT3 (k = 0.72). DATA
      CONCLUSION: We found moderate to substantial agreement in assigning the PI-RADS
      v2 categories and assessing the spectrum of cancers found on whole-mount
      histology, with category 4 as the most reproducible cutoff for csPCa. Readers'
      experience influenced interreader agreement and cancer detection rate. LEVEL OF
      EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017.

PMID- 30187601
TI  - Vitamin D deficiency and infection risk in kidney transplant recipients: A single
      center cohort study.
AB  - BACKGROUND: Recent studies have reported an increased susceptibility to infection
      among vitamin D-deficient kidney transplant (KT) recipients, although
      methodological concerns remain. METHODS: Serum 25-hydroxyvitamin D (25(OH)D)
      levels were measured in 246 KT recipients at post-transplant months 1, 3, 6 and
      12. Vitamin D status was analysed in terms of deficiency (Endocrine Society [<20
      ng/mL] and Institute of Medicine [IoM, <12 ng/mL] criteria) and as a continuous
      variable. Cox models for overall, bacterial and opportunistic infection were
      adjusted for nutritional status and immunosuppression-related covariates.
      RESULTS: Median serum 25(OH)D increased from month 1 (10.5 ng/mL) to month 6
      (16.3 ng/mL; P-value = 0.001). Prevalence of vitamin D deficiency at month 1
      ranged from 87.0% to 61.0% (depending on the diagnostic criteria) and
      significantly decreased over the next months. After adjustment for age and
      nutritional status, vitamin D deficiency (serum 25(OH)D < 12 ng/mL) at month 1
      was an independent risk factor for overall (hazard ratio [HR]: 1.70; 95%
      confidence interval [CI]: 1.08-2.69; P-value = 0.023) and opportunistic infection
      (HR: 4.05; 95% CI: 1.57-10.46; P-value = 0.004), but not for bacterial infection.
      A protective effect for overall (adjusted HR: 0.76; 95% CI: 0.63-0.93; P-value =
      0.007) and opportunistic infection (adjusted HR: 0.62; 95% CI: 0.45-0.86; P-value
      = 0.004) was observed when 25(OH)D levels were analyzed per one-quartile
      increases. CONCLUSIONS: Vitamin D status influences the risk of infection among
      KT recipients, with the association being particularly evident for opportunistic
      events and mainly restricted to the early post-transplant period.

PMID- 30187602
TI  - Neonatal varicella: Probable transmission from a vaccinated mother.

PMID- 30187603
TI  - New viral biomarkers for Hepatitis B: Are we able to change practice?
AB  - The management of chronic hepatitis B virus (HBV) infection is challenged by its
      varying natural course and its stealthy nature. Not all HBV-infected patients
      will develop complications of infection; however, it is of utmost importance to
      identify patients who are at risk and require antiviral treatment and/or close
      surveillance. Hepatic inflammation and quantification of HBV DNA have guided
      treatment decisions in the last decade, and these guided interventions have been
      shown to reduce liver-related complications and death. Data on the quantification
      of additional HBV markers such as hepatitis B surface antigen (HBsAg), hepatitis
      B core-related antigen (HBcrAg) and hepatitis B virus RNA (HBV RNA) have
      accumulated in recent years. Here, we review the current evidence of how to use
      these markers and discuss open issues that require additional research.

PMID- 30187604
TI  - Switching to peginterferon for chronic hepatitis B patients with hepatitis B e
      antigen seroconversion on entecavir - A prospective study.
AB  - Nucleos(t)ide analogues (NA) are effective in suppressing hepatitis B virus (HBV)
      replication, but most patients require long-term treatment. This study aimed to
      investigate switching to peginterferon as a strategy to stop NA. Hepatitis B e
      antigen (HBeAg)-positive chronic hepatitis B patients who developed HBeAg
      seroconversion during NA treatment were studied. All patients received open-label
      peginterferon alfa-2a 180 MUg/wk for 48 weeks, and NA was stopped at week 4 of
      peginterferon treatment. The primary endpoint was sustained response, which was
      defined as negative HBeAg, positive anti-HBe and HBV DNA <2000 IU/mL at week 72.
      Other secondary endpoints including HBsAg loss at week 72 were also studied.
      Forty-one patients treated with entecavir for 56 +/- 23 months were recruited.
      Sustained response was achieved in 30 patients (73%, 95% confidence interval 58%
      84%). At week 72, 31 (76%) patients had HBeAg seroconversion, 56 (23%) patients
      had undetectable HBV DNA, 31 (76%) patients had normal ALT, and 6 patients (15%)
      had HBsAg loss. Baseline HBsAg level was the best predictor for both sustained
      response and HBsAg loss; the best HBsAg cut-off for sustained response was <1500
      IU/mL and that for HBsAg loss was <500 IU/mL by receiver operating characteristic
      curve analysis. Twenty-two of 25 (88%) patients with baseline HBsAg <1500 IU/mL
      had sustained response. Five of 10 (50%) patients with baseline HBsAg <500 IU/mL
      developed HBsAg loss. Switching to peginterferon can be considered as a treatment
      option in NA-treated patients with HBeAg seroconversion, particularly among those
      with lower HBsAg levels.

PMID- 30187606
TI  - A Unified Approach to Customized Chiral Carbon-Bridged ansa-Metallocenes.
AB  - Chiral ansa-metallocenes are privileged catalysts for a range of stereoselective
      transformations. Their synthesis, however, has remained a tremendous challenge,
      which has prevented a broad and systematic exploration for applications in
      synthesis and catalysis. A modular approach to such ansa-metallocenes that
      enables a facile modification of the ring substitution and the ligand bridge, as
      well as the introduction of various core metals, is described. The complexes were
      formed with good rac-selectivity and could be isolated with high purity. The
      strength of the approach was demonstrated by the synthesis of several new and
      previously known complexes, including a unique helical chiral ansa-metallocene.
      Using a chiral ligand, a moderate central-to-planar chirality transfer was
      observed.

PMID- 30187605
TI  - Laparoscopic drainage of splenic abscess to avoid splenectomy.

PMID- 30187608
TI  - Commentary on article on clinical efficacy of oral finasteride by Won, Lew, and
      Sim.

PMID- 30187607
TI  - A systematic review on models of care effectiveness and barriers to Hepatitis C
      treatment in prison settings in the EU/EEA.
AB  - Hepatitis C prevalence in prison populations is much higher than in the
      community. Effective hepatitis C treatment within this population does not only
      have a direct individual health benefit, but may lead to substantial community
      dividend. We reviewed available evidence on hepatitis C treatment in prison
      settings, with a focus on the European Union/European Economic Area. A systematic
      review of the literature (PubMed, EMBASE, Cochrane library) was performed and
      complemented with searches for conference abstracts and grey literature. Thirty
      four publications were included reporting on the effectiveness, acceptability and
      economic aspects of hepatitis C virus treatment models of care to achieve
      treatment completion and sustained viral response in prison settings. Available
      evidence shows that hepatitis C treatment in prison settings is feasible and the
      introduction of direct-acting antivirals will most likely result in increased
      treatment completion and better clinical outcomes for the prison population,
      given the caveats of affordability and the need for increased funding for prison
      health, with the resulting benefits accruing mostly in the community.

PMID- 30187609
TI  - Vistriterpenoids A and B, Two New 24-Nor-oleanane Triterpenoids from Dodonaea
      viscosa.
AB  - Two new triterpenoids, vistriterpenoids A (1) and B (2), and four known ones,
      were acquired from Dodonaea viscosa. Compounds 1 and 2 represent the 24-nor
      oleanane triterpenoids isolated from the genus Dodonaea for the first time. Their
      structures were identified based on extensive spectroscopic methods. Compounds 1,
      2, 5, and 6 exerted inhibitory activities against PTP1B in vitro.

PMID- 30187610
TI  - Computational Studies on Biosynthetic Carbocation Rearrangements Leading to
      Quiannulatene: Initial Conformation Regulates Biosynthetic Route,
      Stereochemistry, and Skeleton Type.
AB  - The results of quantum chemical calculations on the mechanism of the carbocation
      cascade of reactions in the biosynthetic pathways leading to the pentacyclic
      sesterterpenes quiannulatene and sesterfisherol provide reasonable answers to
      several persistent mechanistic questions in sesterterpene biosynthesis,
      including: 1) the reaction pathways of the multicyclic ring system construction
      and skeletal rearrangements, 2) the mechanism of triquinane skeleton formation,
      which requires more complicated rearrangements than previously proposed, 3) the
      stereochemistry of the final carbocation intermediate, and 4) the determining
      factor of biosynthetic selection for either 5/6/4/6/5 or 5/6/5/5/5 pentacyclic
      skeleton formation. This in-depth mechanistic study on sesterterpene biosynthesis
      revealed that the shape of the final product and the type of triquinane skeleton
      formed are regulated by the stereochemistry and conformation of the common
      starting material, geranylfarnesyl diphosphate (GFPP).

PMID- 30187611
TI  - Extracellular vesicles from hepatitis B patients serve as reservoir of hepatitis
      B virus DNA.

PMID- 30187613
TI  - Extending the cascade: identification of a mitogen-activated protein kinase
      phosphatase playing a key role in rice yield.

PMID- 30187612
TI  - Long-term follow-up of patients treated with entecavir and peginterferon add-on
      therapy for HBeAg-positive chronic hepatitis B infection: ARES long-term follow
      up.
AB  - Addition of peginterferon alpha (PEG-IFN add-on) to entecavir (ETV) treatment
      after a short lead-in phase results in more response than ETV monotherapy in
      HBeAg-positive chronic hepatitis B infection (CHB). This study is the first to
      assess long-term efficacy of this treatment strategy. Patients who received ETV
      +/- 24 weeks of PEG-IFN add-on in a global trial (ARES study) and completed
      follow-up were eligible to participate in this observational LTFU study if they
      had at least one combined HBeAg and HBV DNA measurement beyond week 96 of the
      ARES study. The primary endpoint was combined response (HBeAg loss and HBV DNA
      <200 IU/mL) at LTFU. In total, 48 patients treated with PEG-IFN add-on and 48
      patients treated with ETV monotherapy were included. The median follow-up
      duration was 226 (IQR 51) weeks, and 86/96 (90%) patients were initial non
      responders. At LTFU, combined response was present in 13 (27%) vs 11 (23%)
      patients (P = 0.81), and 1 log10  HBsAg decline in 59% vs 28% (P = 0.02) for PEG
      IFN add-on and ETV monotherapy, respectively. In 41 initial non-responders who
      continued ETV therapy, combined response at LTFU was present in 9 patients (PEG
      IFN add-on: 5/22 [23%]; ETV monotherapy: 4/19 [21%]). Beyond week 96 of follow
      up, rates of serological response became comparable between PEG-IFN add-on and
      ETV monotherapy. Although in this LTFU study initial non-responders were
      overrepresented in the add-on arm, PEG-IFN add-on possibly leads rather to
      accelerated HBeAg loss than to increased long-term HBeAg loss rates.

PMID- 30187614
TI  - Child restraint orientation: Accuracy of information on Japanese websites.
AB  - BACKGROUND: Child restraints provide maximum protection when used appropriately,
      but seat orientation (rear- or forward-facing) according to child development is
      often misunderstood, and the information provided can be inaccurate. This study
      examined the accuracy of information in Japanese on seat orientation found on the
      Internet. METHODS: We searched websites in Japanese on Google regarding
      information on recommended seat orientation for young children and examined the
      first 50 sites based on the search rankings for the criteria on when to allow
      children to ride in forward-facing seats. RESULTS: None of the examined websites
      included information that was consistent with the recommendation of the Japan
      Pediatric Society (i.e. age must be at least 1 year old and weight, at least 10
      kg). The most common mistake was that weight alone could determine timing.
      CONCLUSIONS: More vigorous efforts are needed to disseminate evidence-based
      information about seat orientation to protect child passengers.

PMID- 30187615
TI  - Abdominal pain, unconsciousness, and skin rash after lung transplantation.
AB  - Long-term success of lung transplantation is limited by allograft dysfunction and
      frequent infections. Varicella zoster virus infection (VZV) is one of the most
      common opportunistic infections among solid organ transplantation recipients.
      However the occurrence of visceral involvement or disseminated disease, as seen
      after bone marrow transplantation, is rare. We report a case of a 59-year-old
      woman who underwent double-lung transplantation with a fatal visceral and
      disseminated varicella zoster virus infection.

PMID- 30187616
TI  - Wheat blast: from its origins in South America to its emergence as a global
      threat.
AB  - Wheat blast was first reported in Brazil in 1985. It spread rapidly across the
      wheat cropping areas of Brazil to become the most important biotic constraint on
      wheat production in the region. The alarming appearance of wheat blast in
      Bangladesh in 2016 greatly increased the urgency to understand this disease,
      including its causes and consequences. Here, we summarize the current state of
      knowledge of wheat blast and aim to identify the most important gaps in our
      understanding of the disease. We also propose a research agenda that aims to
      improve the management of wheat blast and limit its threat to global wheat
      production.

PMID- 30187617
TI  - Immuno-affinity Amperometric Detection of Bacterial Infections.
AB  - A combination of an immuno-affinity enrichment strategy and sensitive
      amperometric read-out was implemented in a point-of-care platform intended for
      bacterial infection analysis. Bacterial cells, selectively captured and enriched
      from complex matrices through immuno-affinity, were detected by amperometric
      monitoring of the redox state of metabolic activity indicators, providing species
      identification and viable-cell quantification. The method was successfully
      employed for the diagnosis of bacterial infections including antimicrobial
      susceptibility testing with only several hours of total working time.

PMID- 30187618
TI  - Volatile Profiling, Insecticidal, Antibacterial and Antiproliferative Properties
      of the Essential Oils of Bursera glabrifolia Leaves.
AB  - The present article describes the chemical composition and biological activities
      of the essential oils of B. glabrifolia leaves obtained in four consecutive years
      (2015-2018). The essential oils contained alpha-terpineol (17.9-29.7 %), alpha
      terpinene (12.6-17.4 %), limonene (14.9-26.8 %) and beta-pinene (2.1-16.7 %) as
      the most abundant volatiles. The essential oils and these volatiles showed a
      significant adulticide activity (p<0.01; LC50 <100 MUg mL-1 ) on the maize weevil
      (Sitophilus zeamais) with a 100 % mortality rate within a period of 5 h. Also,
      the essential oils showed a strong antibacterial activity on Enterococcus
      faecalis ATCC 29212 (MIC, 132.7-173.6 MUg mL-1 ) and Helicobacter pylori ATCC
      43504 (MIC, 74.8-199.2 MUg mL-1 ). The assessment of the main volatiles revealed
      alpha-terpineol as the principal antibacterial agent (MIC, 78.6-149.7 MUg mL-1 ).
      Similarly, the essential oils exhibited a substantial in vitro antiproliferative
      activity on the human prostate cancer cell lines PC-3 (LC50 , 15.2-19.4 MUg mL-1
      ), the human ovarian carcinoma cell lines OVCAR-3 (LC50 , 27.3-53.7 MUg mL-1 )
      and the myelogenous leukemia cell lines K-562 (LC50 , 32.4-75.9 MUg mL-1 ). alpha
      Terpineol (LC50 , 32.4-75.9 MUg mL-1 ) exhibited the strongest antiproliferative
      effect on these cancer cell lines (LC50 , 22.4-48.1 MUg mL-1 ).

PMID- 30187619
TI  - High resolution melting analysis for the characterization of lineage II Listeria
      monocytogenes serovars 1/2a and 1/2c based on single nucleotide polymorphisms
      identification within the Listeria Pathogenicity Island-1 and inlAB operon: a
      novel approach for epidemiological surveillance.
AB  - AIMS: A high resolution melting (HRM) assay was developed for characterizing
      lineage II Listeria monocytogenes based on the amplification and the melting
      profiles analysis of 81 fragments targeting the region from the prs to ldh loci,
      including the Listeria Pathogenicity Island-1 (LIPI-1) genes and the inlAB
      operon. METHODS AND RESULTS: Real-time PCR and HRM protocols were standardized
      using 10 replicate assays from L. monocytogenes EGD-e reference strain (serovar
      1/2a). Twenty wild-type isolates of serovar 1/2a and two of serovar 1/2c were
      tested, and differences between EGD-e strain and the wild-type isolates were
      defined if the melting temperature (Tm ) of an amplicon was not within the lower
      and the upper limits calculated from replicate testing on EGD-e. The analysis
      revealed 17 and 19 HRM profiles with respect to prs/LIPI-1/ldh and inlAB target
      regions (Simpson's Index of Diversity 0.979 and 0.983) respectively. The 1/2c
      cultures showed 98.1% similarity to melting characteristics with EGD-e, whilst
      1/2a isolates had the greatest heterogeneity that was related to inlA, inlB and
      actA genes. Sequencing of amplicons generating different Tm values from EGD-e
      confirmed the presence of point mutations. CONCLUSIONS: This method was useful
      for L. monocytogenes subtyping based on single nucleotide polymorphisms detection
      through the melting behaviour analysis of main virulence genes. SIGNIFICANCE AND
      IMPACT OF THE STUDY: The study underlines the effectiveness of HRM in
      differentiating L. monocytogenes strains with high discriminatory power, thus
      rendering it useful for epidemiological surveillance.

PMID- 30187621
TI  - Screening haemodialysis patients for hepatitis C in Vietnam: The inconsistency
      between common hepatitis C virus serological and virological tests.
AB  - Selecting the appropriate screening method and interval for the early detection
      of hepatitis C virus (HCV) infection in low-resourced haemodialysis settings is a
      challenge. The challenge occurs when patients are classified as HCV-RNA positive
      but negative to HCV-core antigen (HCV-coreAg), anti-HCV and genotyping tests. We
      aim to clarify the inconsistency between HCV-RNA, HCV-coreAg, anti-HCV and HCV
      genotyping tests in haemodialysis patients and determine the reliability of HCV
      coreAg as a routine two-monthly screening strategy. Haemodialysis patients were
      tested every 2 months between 2012 and 2014 at the largest district haemodialysis
      unit in Ho Chi Minh City, Vietnam, for aminotransferases, anti-HCV antibodies,
      HCV-coreAg, HCV-RNA and HCV genotype. HCV-coreAg and anti-HCV results were tested
      against HCV-RNA for sensitivity, specificity, positive predictive value (PPV),
      negative predictive value (NPV). All 201 patients participated in the study. The
      HCV-coreAg test performed better than the anti-HCV test for sensitivity (100% vs
      31%), NPV (100% vs 90%) and accuracy (100% vs 90%). The HCV-coreAg and anti-HCV
      tests performed no differently for specificity (100% and 98%, respectively) or
      PPV (100% and 73%, respectively). Kappa values for HCV-coreAg and anti-HCV tests
      were 1 and 0.39, respectively. Early detection of HCV for the purpose of
      infection prevention requires a high level of sensitivity and HCV-coreAg
      performed better in our chronic haemodialysis population as a two-monthly
      screening method than routine anti-HCV testing. HCV-coreAg test is less labour
      intensive with a higher level of accuracy in patients with low viral loads making
      it cost effective for low-resourced settings. Repeating genotyping may be
      required in HCV-coreAg positive patients with a low viral load.

PMID- 30187620
TI  - Glucagon-like peptide-1 receptor agonists for antipsychotic-associated cardio
      metabolic risk factors: A systematic review and individual participant data meta
      analysis.
AB  - AIMS: To evaluate if glucagon-like peptide-1 receptor agonists (GLP-1RAs) reduce
      antipsychotic-associated body weight gain in patients with schizophrenia, when
      compared to controls. MATERIALS AND METHODS: We systematically searched
      PubMed/EMBASE/PsycINFO/Cochrane using the search terms '(antipsychotic and GLP
      1RA)'. Individual participant data from studies randomizing patients to GLP-1RA
      or control were meta-analysed. The primary outcome was difference in body weight
      between GLP-1RA and control; secondary outcomes included cardio-metabolic
      variables and adverse drug reactions (ADRs). Multiple linear regression was
      conducted including sex, age, psychosis severity, metabolic variable, ADRs, and
      GLP-1RA agent. RESULTS: Three studies (exenatide once-weekly = 2; liraglutide
      once-daily = 1) provided participant-level data (n = 164, age = 40.0 +/- 11.1
      years, body weight = 105.8 +/- 20.8 kg). After 16.2 +/- 4.0 weeks of treatment,
      body weight loss was 3.71 kg (95% CI = 2.44-4.99 kg) greater for GLP-1RA versus
      control (p < 0.001), number-needed-to-treat >=5% body weight loss = 3.8 (95% CI =
      2.6-7.2). Waist circumference, body mass index, HbA1c, fasting glucose and
      visceral adiposity were each significantly lower with GLP-1RA. Sex, age,
      psychosis severity, nausea, any ADR, and GLP-1RA agent did not significantly
      impact outcomes. Body weight loss with GLP-1RAs was greater for
      clozapine/olanzapine-treated patients (n = 141) than other antipsychotics (n =
      27) (4.70 kg, 95% CI = 3.13-6.27 vs. 1.5 kg, 95% CI = -1.47-4.47) (p < 0.001).
      Nausea was more common with GLP-1RAs than control (53.6% vs. 27.5%, p = 0.002,
      number-needed-to-harm = 3.8). CONCLUSION: GLP-1RAs are effective and tolerable
      for antipsychotic-associated body weight gain, particularly clozapine/olanzapine
      treated patients. With few included patients, further studies are required before
      making routine use recommendations for GLP-1RAs.

PMID- 30187622
TI  - Calcium(II)-Catalyzed Intermolecular Hydroarylation of Deactivated Styrenes in
      Hexafluoroisopropanol.
AB  - A challenging catalytic hydroarylation of highly electron deficient styrenes has
      been developed on the basis of efficient cooperation between a calcium(II)
      triflimide salt and hexafluoroisopropanol (HFIP). This method affords a large
      variety of diaryl alkanes, notably diaryl ethanes, in good to excellent yields,
      and is simple to implement and compatible with various functional groups.
      Furthermore, DFT calculations and deuterium labeling experiments were conducted
      to elucidate the function of this promoter system.

PMID- 30187623
TI  - An exceptional uterine inversion in a virgo patient affected by submucosal
      leiomyoma: Case report and review of the literature.
AB  - Inversion of the uterus is quite a rare obstetric (puerperal) or gynecological
      (non-puerperal) condition. Non-puerperal type may be benign or malign mass
      induced or idiopathic. To the best of our knowledge, this is the first case with
      a large review of literature of uterine inversion in a patient without sexual
      experience. We report the case of a 52-year-old, unmarried virgo woman, affected
      by schizophrenia, was referred to our emergency room for evidence of a mass
      outside of the vaginal introitus, combined with vaginal bleeding and abdominal
      pain. The patient underwent vaginal myoma resection and abdominal hysterectomy
      with bilateral adnexectomy. The diagnosis of uterine inversion was confirmed
      during operation. Diagnosis of uterine inversion is often not easy and imaging
      studies might be helpful. Despite the rarity, uterine non-puerperal inversion is
      possible: for this reason, it is necessary to perform appropriate, conservative
      treatment, especially in women affected by benign myomas and with a desire for
      pregnancy.

PMID- 30187624
TI  - Comprehensive exploration of the enzymes catalysing oxygen-involved reactions and
      COGs relevant to bacterial oxygen utilization.
AB  - To better understand the mechanisms of bacterial adaptation in oxygen
      environments, we explored the aerobic living-associated genes in bacteria by
      comparing Clusters of Orthologous Groups of proteins' (COGs) frequencies and gene
      expression analyses and 38 COGs were detected at significantly higher frequencies
      (p-value less than 1e-6) in aerobes than in anaerobes. Differential expression
      analyses between two conditions further narrowed the prediction to 27 aerobe
      specific COGs. Then, we annotated the enzymes associated with these COGs.
      Literature review revealed that 14 COGs contained enzymes catalysing oxygen
      involved reactions or products involved in aerobic pathways, suggesting their
      important roles for survival in aerobic environments. Additionally, protein
      protein interaction analyses and step length comparisons of metabolic networks
      suggested that the other 13 COGs may function relevantly with the 14 enzymes
      corresponding COGs, indicating that these genes may be highly associated with
      oxygen utilization. Phylogenetic and evolutionary analyses showed that the 27
      COGs did not have similar trees, and all suffered purifying selection pressures.
      The divergent times of species containing or lacking aerobic COGs validated that
      the appearing time of oxygen-utilizing gene was approximately 2.80 Gyr ago. In
      addition to help better understand oxygen adaption, our method may be extended to
      identify genes relevant to other living environments.

PMID- 30187626
TI  - Commentary on adverse effects of isotretinoin article by Brezenski et al.

PMID- 30187625
TI  - Seasonal succession of small planktonic eukaryotes inhabiting surface waters of a
      coastal upwelling system.
AB  - Small eukaryotes (0.2-20 MUm cell-size) represent a significant fraction of the
      microbial plankton community in shelf waters of NW-Spain. The community
      composition of small eukaryotes living at the surface and at the base of the
      photic zone was analysed by means of 18S rDNA high-throughput sequencing on a
      circa-monthly basis over a 23 months period. Ostreococcus was the most abundant
      taxon in surface waters, showing marked peaks in read abundance in spring and
      late summer, while Syndiniales dominated at the base of the photic zone. A well
      defined seasonal pattern of community composition, linked to the succession of
      the dominant taxa, was found in surface waters. Seasonality was less apparent at
      the base of the euphotic zone. Temporal changes in abiotic factors significantly
      correlated with changes in community composition in surface (r = 0.71) and at the
      base of the photic zone (r = 0.38). Changes in community composition
      significantly correlated with changes in community function-related variables
      (including biomass, primary production and respiration) only in surface water (r
      = 0.36). Co-occurrence network analyses revealed 45 significant interspecies
      associations among the 50 most abundant taxa with highly connected OTUs belonging
      to cryptophyceans. The network topology, with small-world characteristics,
      suggests a stabilizing role of biotic interactions to environmental disturbance.

PMID- 30187628
TI  - 2,3-Dihydrofurans as Potential Cytotoxic and Antibacterial Agents: Tandem
      Knoevenagel-Michael Cyclization for the Synthesis of 2,3-Dihydrofurans by Using
      alpha-Tosyloxy Ketone Precursors.
AB  - Novel 2,3-dihydrofuran derivatives were synthesized through a tandem Knoevenagel
      Michael cyclization in good yield by reacting alpha-tosyloxy ketone, 5,5-dimethyl
      1,3-cyclohexanedione, and various aldehydes in the presence of phthalazine in
      acetonitrile. These compounds were subjected to in vitro antibacterial screening
      against eight micro-organisms by using diffusion method and also in vitro
      cytotoxicity screening against four human cancerous cell lines by applying MTT
      assay. Some of the compounds showed impressive activities.

PMID- 30187629
TI  - How classmates' stress affects student's quality of motivation.
AB  - Over the last decades, more and more adolescents and children feel chronically
      stressed, which negatively affects their school performance. However, less is
      known whether classmates' general stress affects an individual student's quality
      of motivation. Therefore, based on conservation of resources theory, this study
      examined the precise interplay between general stress and the quality of
      motivation for students in high- and low-tracking schools considering potential
      context effects. Results of multilevel multigroup structural equation models with
      questionnaire data from 1,088 German students identified differences in the
      relation between general stress and quality of motivation for students from
      different school forms on both the within and between level.

PMID- 30187627
TI  - Dichorionic-diamniotic twins: One case each of esophageal atresia and congenital
      pulmonary airway malformation.

PMID- 30187630
TI  - Systemic use of calcium channel blockers associated with less increase in central
      retinal thickness after uncomplicated cataract surgery.
AB  - PURPOSE: To examine the role of systemic medication on the risk of pseudophakic
      cystoid macular edema (PCME) following uneventful cataract surgery. METHODS: A
      total of 269 eyes undergoing routine cataract surgery. Spectral-domain optical
      coherence tomography imaging was conducted before surgery and at 28 days.
      Information about medication of the participants was gathered from The National
      Archive of Health Information (Kanta), an electronic pharmaceutical database.
      RESULTS: Systemic medication with angiotensin converting enzyme
      inhibitor/angiotensin II receptor antagonists (p < 0.001), beta-blockers (beta
      blockers) (p = 0.002), calcium channel blockers (CCBs) (p < 0.001), nitrates (p
      =0.021) and lipophilic HMG-CoA reductase inhibitors (statins) (p < 0.001) were
      more frequently prescribed to diabetic compared with nondiabetic patients. In
      eyes with steroid monotherapy (N = 135), concomitant systemic medication with
      beta-blockers (12.9 +/- 24.0 MUm versus 28.6 +/- 59.5 MUm, p = 0.045), CCBs (12.0
      +/- 22.1 MUm versus 26.3 +/- 55.6 MUm, p = 0.041) and statins (12.9 +/- 22.8 MUm
      versus 30.0 +/- 61.9 MUm, p = 0.038) attenuated a change in central retinal
      thickness (CRT) when compared to patients not receiving medication. In
      multivariable analysis, the use of CCBs remained as an independent protective
      factor against macular swelling at 28 days (-0.23; 95% CI [-0.43 to -0.04]; p =
      0.021), when all systemic medications showing statistical significance were
      included (i.e. beta-blockers, CCBs and statins) together with diabetes status. In
      eyes with nonsteroidal anti-inflammatory drug (NSAID) monotherapy (N = 67) and
      steroid and NSAID combination therapy (N = 67), CRT increase was moderate both
      with and without use of systemic medications. CONCLUSION: Systemic vasoactive
      medication may be protective against CRT change induced by cataract surgery in
      eyes at risk of PCME such as those with postoperative steroid monotherapy.

PMID- 30187631
TI  - Statistics in ophthalmology revisited: the (effect) size matters.
AB  - The association of biomedical sciences with mathematics is inextricable and
      undeniable. It should be considered that gaining confidence or strong belief
      within the framework of a scientific experiment - in the 'compulsory' marriage
      with statistics - does not mean total and undisturbed certainty. The null
      hypothesis significance testing (NHST) has been the kernel of statistical data
      analysis for a long period. Medicine is making use of it in a very wide range.
      The main problem in NHST arises out of a dichotomic perception of reality.
      Scientific reasoning was biased in the aftermath of the uncritical, almost
      dogmatic, trust in a level of statistical significance, namely a p-value, defined
      as 'the dictating paradigm of p-value'. The level of statistical significance (p
      value) is not completely plausible and objective; it cannot be equated with the
      nature of a phenomenon or population characteristics. The p-value refers directly
      to a formulated hypothesis only, that is the probability of observing a given
      outcome under the condition posited by a specific null hypothesis and given a
      specific model of the distribution of outcomes under the null hypothesis. Experts
      claim that unjustified conclusions and guidelines have become the bane of many
      scientific journals. Investigators should be able to interpret study results in a
      broad context and look at them critically. Statistics indeed is a leaven to
      further scientific discussion, not its conclusion. It is not easy to abandon the
      p-value. Lots of researchers recommended an ecumenical approach to the
      statistical analysis of research data, for example analyses of the same results
      using a variety of statistical procedures. Many of them express the view that a
      threshold level of statistical significance should be lower than p < 0.05. To
      enhance the plausibility and true scientific value of research works,
      investigators should also take into consideration the effect size along with its
      confidence limits. The effect size is a kind of added value and should be
      determined a priori. Account must be taken of their origin, conditioning (medical
      knowledge), as well as specific implications in clinical practice. The effect
      size makes possible to compare results of various research works. It is argued
      that to the rescue for modern science can come research works that bear the stamp
      of reproducibility, for example studies conducted in several independent centres,
      based on coherent and meticulous methodology, or data from various centres typed
      in one spotless big database and submitted to rigorous and deliberate multilevel
      statistical analyses.

PMID- 30187632
TI  - Efficacy of intermittent empagliflozin supplementation on dietary self-management
      and glycaemic control in patients with poorly controlled type 2 diabetes: A 24
      week randomized controlled trial.
AB  - AIMS: To explore the effects of intermittent use of empagliflozin, a sodium
      glucose co-transporter-2 inhibitor, on dietary self-management and glycaemic
      control in patients with inadequately controlled type 2 diabetes. MATERIALS AND
      METHODS: We conducted a prospective, randomized, open-label, blinded-endpoint,
      parallel-group, comparative clinical trial of 50 patients with type 2 diabetes,
      treated with no more than three oral antidiabetic drugs (glycated haemoglobin
      [HbA1c] >=52 mmol/mol but <86 mmol/mol). The participants were randomized to take
      10 mg/d empagliflozin either every day (regular group, n = 25) or on the day on
      which they considered they had overeaten (intermittent group, n = 25) for 24
      weeks. We limited empagliflozin prescription to half of the required period in
      the intermittent group. The primary endpoint was change in HbA1c at the end of
      the 24-week treatment period relative to baseline. The secondary outcomes
      included changes in body weight, daily energy intake and diabetes treatment
      related quality of life (QoL). Energy intake was assessed using a diet-specific
      validated questionnaire rather than actual assessments of food intake. RESULTS:
      The intake rate of empagliflozin was 96.7 +/- 7.2% for the regular group and 45.7
      +/- 7.0% for the intermittent group. Interestingly, DeltaHbA1c was identical in
      the two groups (-0.64 +/- 0.19% and - 0.65 +/- 0.17%, respectively). Body weight
      decreased (-2.72 +/- 0.52 and - 1.50 +/- 0.45 kg, respectively) and diabetes
      treatment-related QoL increased significantly from baseline in both groups.
      Energy intake, however, decreased significantly only in the intermittent group (
      221.0 +/- 108.3 kcal/d). CONCLUSIONS: Intermittent empagliflozin supplementation
      is a useful therapeutic option that empowers dietary self-management, improves
      glycaemic control and is accompanied by body weight loss and an increase in
      diabetes treatment-related QoL in patients with inadequately controlled type 2
      diabetes.

PMID- 30187633
TI  - The role of conserved proteins DrpA and DrpB in nitrate respiration of Thermus
      thermophilus.
AB  - In many Thermus thermophilus strains, nitrate respiration is encoded in mobile
      genetic regions, along with regulatory circuits that modulate its expression
      based on anoxia and nitrate presence. The oxygen-responsive system has been
      identified as the product of the dnrST (dnr) operon located immediately upstream
      of the nar operon (narCGHJIKT), which encodes the nitrate reductase (NR) and
      nitrate/nitrite transporters. In contrast, the nature of the nitrate sensory
      system is not known. Here, we analyse the putative nitrate-sensing role of the
      bicistronic drp operon (drpAB) present downstream of the nar operon in most
      denitrifying Thermus spp. Expression of drp was found to depend on the master
      regulator DnrT, whereas the absence of DrpA or DrpB increased the expression of
      both DnrS and DnrT and, concomitantly, of the NR. Absence of both proteins made
      expression from the dnr and nar operons independent of nitrate. Polyclonal
      antisera allowed us to identify DrpA as a periplasmic protein and DrpB as a
      membrane protein, with capacity to bind to the cytoplasmic membrane. Here, we
      propose a role for DrpA/DrpB as nitrate sensors during denitrification.

PMID- 30187634
TI  - Early oral feeding after colorectal surgery: A mixed methods study of knowledge
      translation.
AB  - AIM: Evidence-based guidelines recommend early oral feeding (EOF) as prescription
      of an unrestricted diet within 24 hours after colorectal surgery. The present
      study aimed to understand local postoperative feeding practices after colorectal
      surgery; identify barriers to EOF implementation; select, tailor and implement
      stakeholder engagement strategies to facilitate EOF uptake; and evaluate changes
      to practice. METHODS: A longitudinal, mixed methods study was undertaken, guided
      by the knowledge-to-action framework. Phase 1 assessed the nature of the problem
      using postoperative diet Audits 1 and 2. In Phase 2, staff interviews identified
      barriers to EOF implementation. Results from Phases 1 and 2 were fed back to
      inform Phase 3 strategies. Knowledge uptake was monitored in Audits 3 and 4.
      Phase 4 evaluated outcomes from Audit 5. RESULTS: In Phase 1, median time to
      commencement of full diet was postoperative Days 4 and 3 in Audits 1 and 2,
      respectively. Phase 2 identified EOF barriers, including disparities in diet
      upgrade practices and variable understanding of hospital diets. In Phase 3,
      planned strategies were implemented to improve EOF (i) educational session
      describing local hospital diets; (ii) consultant decision to prescribe a full
      diet on operation notes; and (iii) educational sessions with nursing staff
      describing changes to EOF practice. In Phase 4, median time to commencement of
      full diet improved to postoperative Day 0. Patients prescribed a full diet on
      operation notes increased from 0% to 82%. CONCLUSIONS: The present study
      successfully identified and overcame local barriers to improve EOF practices to
      align with guideline recommendations.

PMID- 30187635
TI  - Emergency department visits for dental problems associated with trauma in
      Alberta: A report between the years 2011 and 2017.
AB  - BACKGROUND/AIMS: Dental trauma represents a significant cause for concern in
      emergency department (ED). The aim of this study was to report on the prevalence
      of ED visits for dental problems associated with trauma (DPAT) in Alberta,
      Canada. The specific objectives were to provide up-to-date information regarding
      ED utilization for dental trauma concerning the demographics of users and
      distribution of ED visits across the Province of Alberta, allowing for an
      assessment of possible trends over the period of time observed. METHODS: Data for
      ED visits in Alberta between January 1, 2011, and December 31, 2017, were
      extracted from the National Ambulatory Care Reporting System (NACRS). Data
      elements pertinent to this analysis include patient demographics, administrative
      information, and diagnosis. Only the main or primary diagnosis of each ED visit
      was included in this analysis using the International Statistical Classification
      of Diseases (ICD-10-CA). RESULTS: There were 71 118 total ED visits for DPAT in
      this time period, with an average of 10 159 visits per year across Alberta.
      Children aged 1-4 years old represented the age-group in both genders with the
      largest number of ED visits, 22.1% of the total number of visits. The number of
      ED visits for DPAT by males 21 years or younger (22 384) was higher than the
      total number of ED visits among females in all age-groups (21 099). The ICD-10-CA
      code S01.5 referring to open wound of lip and oral cavity was by far the most
      prevalent diagnosis, representing 57.6% of the total visits during the period
      investigated. CONCLUSIONS: This population-based report quantifies the rates and
      frequency of ED utilization for DPAT in the province of Alberta, Canada. The
      information gathered is important to support injury prevention initiatives using
      a population-based approach targeting the high-risk groups of the population
      identified by this study.

PMID- 30187636
TI  - Less might be more: are disposable gloves and gowns necessary for cataract
      surgery?

PMID- 30187637
TI  - Comparison of the regenerative effect of adipose-derived stem cells, fibrin glue
      scaffold, and autologous bone graft in experimental mandibular defect in rabbit.
AB  - BACKGROUND/AIMS: One of the main concerns for maxillofacial and orthopedic
      surgeons is finding a method to improve regeneration of large craniofacial bone
      defects. The aim of this study was to investigate the healing and regenerative
      effects of fibrin glue associated with adipose-derived stem cells (ADSCs) and
      fibrin glue scaffold alone with autologous bone grafts in experimental mandibular
      defects of the rabbit. METHODS: Bilateral uni-cortical osteotomies were performed
      in the mandible of 20 male Dutch rabbits. The animals were randomly divided into
      2 equal groups. In one group, the defect on the right side was treated by fibrin
      glue associated with ADSCs and the defect on the other side remained as the
      control. In another group, the defect on the right side was treated with fibrin
      glue and on the left side with autologous bone graft. After 28 and 56 days, five
      rabbits from each group were evaluated by computed tomography (CT) and
      histopathological examinations. RESULTS: Coronal CT showed a remarkable
      reconstruction of cortical bone in the fibrin glue associated with ADSCs group at
      28 and 56 days post-surgery. Histopathologically, new cortical bony bridge
      formation was seen increasingly in the fibrin glue, fibrin glue associated with
      ADSCs, and autologous bone graft groups after 28 days. Statistical analysis of
      the thickness of new cortical bone in the treatment versus control groups showed
      a significant difference between fibrin glue alone and fibrin glue associated
      with ADSCs groups (P = 0.02). No significant difference was found between the
      fibrin glue associated with ADSCs and the autologous bone graft groups (P >
      0.05). CONCLUSIONS: The healing process had a significant increase in the
      thickness of new cortical bone when fibrin glue scaffold associated with ADSCs
      was used.

PMID- 30187638
TI  - Aqueous cytomegalovirus DNA and interleukin-8 determination in management of
      cytomegalovirus retinitis.

PMID- 30187639
TI  - Effect of Ahasl1-1 and Ahasl1-4 alleles on herbicide resistance and its
      associated dominance in sunflower.
AB  - BACKGROUND: Acetohydroxyacid synthase large subunit 1 (Ahasl1) is a multiallelic
      locus involved in herbicide resistance in sunflower. Ahasl1-1 and Ahasl1-4
      alleles harbor different point mutations that lead to different amino acid
      substitutions (Ala205Val and Trp574Leu, respectively). The objectives of this
      work were to evaluate the effect of these alleles at the enzymatic and whole
      plant levels, and to determine the dominance relationships for imazapyr and
      metsulfuron-methyl herbicides. RESULTS: Resistant near-isogenic lines showed
      significantly lower specific AHAS activity than susceptible near-isoline.
      However, kinetic studies indicated that mutations did not change AHAS pyruvate
      affinity. Dose-response for six near-isolines carrying different combinations of
      Ahasl1-1 and Ahasl1-4 alleles and two herbicides (imazapyr and metsulfuron
      methyl) were evaluated at whole-plant and enzymatic levels. Ahasl1-1 allele
      conferred moderate resistance to imazapyr and low resistance to metsulfuron
      methyl. Conversely, Ahasl1-4 allele endowed high levels of resistance for both
      herbicides. Dominance of resistance at whole-plant level showed a semi-dominant
      behavior among the alleles for both herbicides. CONCLUSION: Ahasl1-4 allele
      confers higher resistance levels than Ahasl1-1 when evaluated with imazapyr and
      metsulfuron-methyl. Dominance estimations suggested that both parental lines
      should carry a resistance trait when developing hybrids. (c) 2018 Society of
      Chemical Industry.

PMID- 30187640
TI  - Hepatitis C virus surveillance and identification of human pegivirus 2 in a large
      Cameroonian cohort.
AB  - The prevalence of chronic hepatitis C virus (HCV) and the presence of human
      pegivirus 2 (HPgV-2) have not been examined in Cameroon, although HCV has been
      associated with HPgV-2 infections previously. Herein we aimed to characterize the
      burden and genetic diversity of HCV and the presence of HPgV-2 in Cameroon.
      Retrospective plasma specimens collected from N = 12 369 consenting subjects in
      South Cameroon from 2013 to 2016 were included in the study. The majority (97.1%)
      of participants were patients seeking health care. All specimens were screened
      for HCV using the Abbott RealTime HCV viral load assay and positive specimens
      with remaining volume were also screened for HPgV-2 antibodies on the Abbott
      ARCHITECT instrument, followed by molecular characterization. Overall, HCV RNA
      was detected in 305 (2.47%; 95% CI: 2.21%-2.75%) specimens. Notably, the
      prevalence of HCV RNA was 9.09% amongst participants over age 40 and 3.81%
      amongst males. Phylogenetic classification of N = 103 HCV sequences identified
      genotypes 1 (19.4%), 2 (15.5%) and 4 (65.1%) within the study cohort. Amongst HCV
      RNA-positive specimens, N = 28 (10.6%; 95% CI: 7.44%-14.90%) specimens also had
      detectable HPgV-2 antibodies. Of these, N = 2 viremic HPgV-2 infections were
      confirmed by sequencing and shared 93-94 median % identity with strains found on
      other continents. This is the first study to determine the prevalence of chronic
      HCV in Cameroon, and the discovery of HPgV-2 in this study cohort expands the
      geography of HPgV-2 to the African continent, indicating a widespread
      distribution exists.

PMID- 30187641
TI  - The impact of extent of internal limiting membrane peeling on anatomical outcomes
      of macular hole surgery: results of a 54-week randomized clinical trial.
AB  - PURPOSE: To compare the anatomical outcomes of different extents of internal
      limiting membrane (ILM) peeling in idiopathic macular hole surgery. METHODS:
      Prospective, parallel-group, randomized clinical trial. A total of 121 eyes of
      121 patients with idiopathic macular hole underwent pars plana vitrectomy, and
      peeling of the ILM with a diameter of two disk diameters (DD) or 4DD based on
      randomization. The main outcome was the proportion of eyes with complete hole
      closure at 12 months. The second outcome was the hole closure grading stratified
      by macular hole closure index (MHCI) at each visit. RESULTS: At 12 months, there
      was no significant difference in anatomical outcomes with complete closure
      achieved in 52 (82.5%) of 63 eyes in the 2DD group and 53 (91.4%) of 58 eyes in
      the 4DD group (p = 0.15). For subjects with MHCI <=0.5 (n = 24), complete closure
      rate was significantly lower in the 2DD group compared to the 4DD group (p =
      0.012; 18.2% versus 75.9%, respectively). Average BCVA was lower in 2DD group
      than 4DD group (p = 0.014). By contrast, when MHCI was >0.5, the complete closure
      rate between the two groups showed no significant difference: 96.2% (50 patients)
      versus 95.6% (43 patients), respectively (p = 0.185). CONCLUSION: In patients
      with idiopathic full-thickness macular hole and MHCI <=0.5, a larger ILM peel of
      4DD tends to achieve better anatomical outcomes than a more limited 2DD peel.

PMID- 30187642
TI  - Intensive community treatment and support "Youth Wraparound" service in Western
      Australia: A case and feasibility study.
AB  - BACKGROUND: Multiple services are often needed to address the needs of young
      people with complex emotional or behavioural needs. The Youth Wraparound model of
      service aims to provide all health and supportive services from one coordinating
      agency. While this has been researched overseas, there are currently few examples
      of this described in the Australian psychiatric context. AIM: To document the
      implementation and evaluation of a Youth Wraparound service which was provided to
      a young person with exceptionally complex and challenging needs for 6 months. A
      single-case study design is presented with an evaluation of the clinical outcome
      and economic costs. METHODS: We present a description of the service context,
      principles of the model of care, implementation process, and an evaluation of
      service utilization data from health and child protection services and mental
      health records. A single-case longitudinal design compared service utilization
      data obtained up to 3 years prior to treatment with data collected one and a half
      years since treatment commenced. RESULTS: There were significant reductions in
      the number of admissions to emergency departments, mental health wards and secure
      units, and improvements in mental health and well-being. Yearly average time in
      institutional settings reduced from 69% to 7%. Cost savings in health utilization
      were estimated at $2 326 790. CONCLUSIONS: The Youth Wraparound model has the
      potential to offer improved clinical outcomes, significant cost savings over
      time, improved coordination between care providers, and an alternative to
      detention or incarceration.

PMID- 30187643
TI  - In Vitro Study of Colon Cancer Cell Migration Using E-Jet 3D Printed Cell Culture
      Platforms.
AB  - The development of accurate and predictive in vitro experimental models of human
      tumors consistent with in vivo tumor microenvironments has garnered great
      attention in modern cancer research. 3D scaffolds are fabricated in this study by
      E-jet 3D printing with the aim of replicating the functionalities of tumor
      microenvironments in vitro which could be applicable as screening platforms for
      novel therapeutic strategies. Tumor protein 53 (p53) plays an important role in
      penetration and migration in 2D cell culture. However, whether or not p53 has the
      same function in 3D cell culture and the underlying mechanisms are poorly
      understood. Results show that p53 deletion significantly decreases the speed of
      migration and proliferation of cancer cells within 3D environments. This study
      unveils aspects of cancer cell motility and migration and the steps involved in
      subsequent cancer metastases, which provides a new perspective and platform for
      the research of tumor metastasis therapy.

PMID- 30187644
TI  - Comprehensive analysis of body composition and insulin traits associated with
      intra-pancreatic fat deposition in healthy individuals and people with new-onset
      prediabetes/diabetes after acute pancreatitis.
AB  - Current knowledge of biomarkers of intra-pancreatic fat deposition (IFD) is
      limited. We aimed to analyse comprehensively body composition and insulin traits
      as biomarkers of IFD in healthy normoglycaemic individuals as well as in
      individuals with new-onset prediabetes or diabetes after acute pancreatitis
      (NODAP). A total of 29 healthy individuals and 34 individuals with NODAP took
      part in this cross-sectional study. The studied biomarkers belonged to the
      following domains: body composition (anthropometric and MRI-derived variables);
      indices of insulin secretion; indices of insulin sensitivity; incretins and
      related peptides; and pancreatitis-related factors. All MRI-derived variables
      (including IFD) were measured using ImageJ software. Univariate and step-wise
      regression analyses were conducted to determine variables that best explained
      variance in IFD. Visceral fat volume and oxyntomodulin were the best biomarkers
      of IFD in normoglycaemic healthy individuals, contributing to 64% variance. The
      Raynaud index was the best biomarker of IFD in individuals with NODAP,
      contributing to 20% variance. Longitudinal studies are warranted to investigate
      the cause and effect relationship between oxyntomodulin and IFD in healthy
      individuals, as well as insulin sensitivity and IFD in individuals with NODAP.

PMID- 30187645
TI  - Species persistence under climate change: a geographical scale coexistence
      problem.
AB  - Forecasting the impacts of climate change on biological diversity requires better
      ways to incorporate competitive interactions into predictions of species' range
      dynamics and persistence. This problem has been studied extensively in a
      different context by theoreticians evaluating the coexistence of species in
      spatially heterogeneous environments. Here, we show how spatial coexistence
      theory can be adapted to provide a mathematical framework for understanding
      species persistence in competitive communities under climate change. We first
      show how the spatial low-density growth rate provides the relevant metric of
      species persistence along a climate gradient. We then analyse a model of multiple
      migrating competitors to show how mechanisms contributing to low-density growth
      rates quantify the effect of different competitive processes on persistence, and
      how these processes change in strength with species' asynchronous migration under
      climate change. Finally, we outline the empirical utility of the framework,
      showing how the theory can scale up from local measurements of species
      performance and competitive interactions to range-scale metrics of persistence.
      Treating species' range dynamics as a geographical-scale coexistence problem
      presents its own set of challenges, but building from a well-established body of
      theory may greatly improve the predictability of species persistence in
      competitive communities under climate change.

PMID- 30187646
TI  - Normative values of retinal vessel oximetry in healthy children against adults.
AB  - BACKGROUND: Retinal oximetry (RO) has been established as a non-invasive method
      to analyse oxygen saturation in retinal vessels. The aim of our study was to
      compare the RO parameters of healthy children to those in adults. METHODS: A
      total of 200 eyes of 104 healthy subjects were examined: 20 eyes of children aged
      <10 years and 62 eyes of children aged 10-19 years were compared to the eyes of
      adult controls from five different age groups (20-29 years:n = 24; 30-39 years:n
      = 32; 40-49 years:n = 15; 50-59 years:n = 20, 60-80 years:n = 27; n indicates the
      number of analysed eyes). The oxygen saturation was estimated with the oxygen
      saturation measurement tool of the Retinal Vessel Analyser (RVA; IMEDOS Systems
      UG, Jena, Germany). The global oxygen saturations, within 1.0-1.5 optic disc
      diameters from the disc margin, in the peripapillary retinal arterioles (A-SO2 ;
      %) and venules (V-SO2 ; %) were estimated and their difference (A-V SO2 ; %) was
      calculated. In addition, we evaluated the mean diameter in all four major retinal
      arterioles (D-A; MUm) and venules (D-V; MUm). The ratio between venular and
      arterial vessel diameter (D-V/A; MUm) was calculated thereafter. For statistical
      evaluation, anova-based linear mixed-effects models were calculated with spss(r)
      . RESULTS: Based on our results, younger children (<10 years) present a
      statistically significant lower A-SO2 and A-V SO2 when compared to adult
      subgroups. The D-A values revealed to be significantly lower in 10 + children
      when compared to the other groups, while the D-V values did not show significant
      differences. CONCLUSION: These data indicate that the retinal oxygen metabolism
      changes throughout lifetime. Therefore, normative data for different age groups
      are mandatory.

PMID- 30187647
TI  - Homology modeling in drug discovery: Overview, current applications, and future
      perspectives.
AB  - Homology modeling is one of the computational structure prediction methods that
      are used to determine protein 3D structure from its amino acid sequence. It is
      considered to be the most accurate of the computational structure prediction
      methods. It consists of multiple steps that are straightforward and easy to
      apply. There are many tools and servers that are used for homology modeling.
      There is no single modeling program or server which is superior in every aspect
      to others. Since the functionality of the model depends on the quality of the
      generated protein 3D structure, maximizing the quality of homology modeling is
      crucial. Homology modeling has many applications in the drug discovery process.
      Since drugs interact with receptors that consist mainly of proteins, protein 3D
      structure determination, and thus homology modeling is important in drug
      discovery. Accordingly, there has been the clarification of protein interactions
      using 3D structures of proteins that are built with homology modeling. This
      contributes to the identification of novel drug candidates. Homology modeling
      plays an important role in making drug discovery faster, easier, cheaper, and
      more practical. As new modeling methods and combinations are introduced, the
      scope of its applications widens.

PMID- 30187648
TI  - Adult attention deficit hyperactivity disorder symptoms and passive leadership:
      The mediating role of daytime sleepiness.
AB  - Passive leadership is attracting empirical interest with the detrimental effects
      of this type of leadership on a broad array of individual and organizational
      outcomes becoming apparent. However, just why leaders would engage in this type
      of nonleadership has received less research attention. We investigate whether and
      how leaders' attention deficit hyperactivity disorder (ADHD) is associated with
      passive leadership. Using a framework specifying how the physiology of sleepiness
      impacts the workplace, we hypothesize that leaders' ADHD is associated with
      passive leadership indirectly through daytime sleepiness. After controlling for
      leaders' age, gender, and preclinical symptoms of depression and anxiety,
      standard ordinary least squares regression procedures were implemented through
      Hayes' PROCESS models. Multisource data from 98 leader-follower groups (M number
      of followers per leader = 4.38, SD = 1.78) showed that the effects of leaders'
      ADHD symptoms on passive leadership were mediated by daytime sleepiness.
      Conceptual, methodological, and practical implications are discussed.

PMID- 30187649
TI  - Associations between the mediterranean diet and sleep in older adults: Results
      from the hellenic longitudinal investigation of aging and diet study.
AB  - AIM: Although there is some evidence of the relationships between sleep
      duration/quality and nutrient and/or food intake, the associations between sleep
      and dietary patterns have been poorly explored. The aim of the present study was
      to evaluate sleep duration and quality in relation to adherence to the
      Mediterranean diet (MeDi), and to investigate the sex- and age-specific
      associations in a population-representative cohort of older adults. METHODS:
      Participants from the Hellenic Longitudinal Investigation of Aging and Diet were
      included. The sample consisted of 1639 adults aged >=65 years. Sleep duration and
      quality were assessed through a self-report questionnaire, whereas adherence to
      the MeDi was evaluated by an a priori score. RESULTS: Sleep quality was
      positively associated with the MeDi in the unadjusted and the adjusted model
      (age, sex, depression, years of education, body mass index, level of physical
      activity and total energy intake were added as covariates). In contrast, sleep
      duration was not associated with MeDi adherence either in the unadjusted or the
      adjusted models. In relation to the age-related associations, sleep quality was
      positively associated with MeDi adherence in those aged <=75 years, and not in
      those aged >75 years. Associations between sleep and MeDi did not differ between
      men and women. CONCLUSIONS: The present results suggest that sleep quality is
      associated with MeDi adherence in older adults; there are also age-specific
      associations between sleep quality and the MeDi. Although additional studies are
      required, improvements in diet quality should be considered in the context of
      sleep management interventions in older individuals. Geriatr Gerontol Int 2018;
      18: 1543-1548.

PMID- 30187650
TI  - Increase in treatment of severe retinopathy of prematurity following a new
      national guideline.

PMID- 30187651
TI  - What bacteria want.
AB  - Bacterial signal transduction systems are responsible for sensing environmental
      cues and adjusting the cellular behaviour and/or metabolism in response to these
      cues. They also monitor the intracellular conditions and the status of the cell
      envelope and the cytoplasmic membrane and trigger various stress responses to
      counteract adverse changes. This surveillance involves several classes of sensor
      proteins: histidine kinases; chemoreceptors; membrane components of the sugar
      phosphotransferase system; adenylate, diadenylate and diguanylate cyclases and
      certain cAMP, c-di-AMP and c-di-GMP phosphodiesterases; extracytoplasmic function
      sigma factors and Ser/Thr/Tyr protein kinases and phosphoprotein phosphatases. We
      have compiled a detailed listing of sensor proteins that are encoded in the
      genomes of Escherichia coli, Bacillus subtilis and 10 widespread pathogens:
      Chlamydia trachomatis, Haemophilus influenzae, Helicobacter pylori, Mycobacterium
      tuberculosis, Mycoplasma pneumoniae, Neisseria gonorrhoeae, Porphyromonas
      gingivalis, Rickettsia typhi, Streptococcus pyogenes and Treponema pallidum, and
      checked what, if anything, is known about their functions. This listing shows
      significant gaps in the understanding of which environmental and intracellular
      cues are perceived by these bacteria and which cellular responses are triggered
      by the changes in the respective parameters. A better understanding of bacterial
      preferences may suggest new ways to modulate the expression of virulence factors
      and therefore decrease the reliance on antibiotics to fight infection.

PMID- 30187653
TI  - Contralateral eye comparison of the long-term visual quality and stability
      between implantable collamer lens and laser refractive surgery for myopia.
AB  - PURPOSE: To investigate the long-term visual quality and stability of implantable
      collamer lens (ICL) and laser refractive surgery (LRS) for myopia. METHODS: This
      study comprised 52 eyes of 26 high-myopia anisometropia patients who were
      suitable for surgical treatment. In each patient, the higher-myopia eye was
      implanted with ICL and the lower-myopia eye was treated with LRS. The patients
      were followed for 3 years. During that time period, uncorrected (UDVA) and
      corrected distance visual acuity (CDVA), refraction, wavefront aberration and
      visual quality were evaluated. RESULTS: The spherical equivalent refractive error
      changed from -14.11 +/- 3.39 D preoperatively to -1.27 +/- 1.05 D 3 years after
      ICL implantation and from -8.75 +/- 2.76 D to -1.12 +/- 1.30 D after LRS. The
      changes in refractive error from 1 month to 3 years were -0.52 and -0.77 D for
      the ICL and LRS groups, respectively. The safety indices (postoperative
      CDVA/preoperative CDVA) were 1.84 +/- 1.00 and 1.32 +/- 0.40, and the efficacy
      indices (postoperative UDVA/preoperative CDVA) were 1.40 +/- 1.10 and 1.11 +/-
      0.44, respectively. The postoperative coma, spherical and total higher-order
      aberrations in the ICL group were lower than those in the LRS group. CONCLUSION:
      Both ICL implantation and LRS are safe and effective procedures for myopia with
      suitable indications, but ICL implantation is more stable. Fewer induced
      aberrations are gained after ICL implantation.

PMID- 30187655
TI  - Prognostic and predictive models in hormone-sensitive prostate cancer.

PMID- 30187652
TI  - GLP-1 suppresses glucagon secretion in human pancreatic alpha-cells by inhibition
      of P/Q-type Ca2+ channels.
AB  - Glucagon is the body's main hyperglycemic hormone, and its secretion is
      dysregulated in type 2 diabetes mellitus (T2DM). The incretin hormone glucagon
      like peptide-1 (GLP-1) is released from the gut and is used in T2DM therapy.
      Uniquely, it both stimulates insulin and inhibits glucagon secretion and thereby
      lowers plasma glucose levels. In this study, we have investigated the action of
      GLP-1 on glucagon release from human pancreatic islets. Immunocytochemistry
      revealed that only <0.5% of the alpha-cells possess detectable GLP-1R
      immunoreactivity. Despite this, GLP-1 inhibited glucagon secretion by 50-70%.
      This was due to a direct effect on alpha-cells, rather than paracrine signaling,
      because the inhibition was not reversed by the insulin receptor antagonist S961
      or the somatostatin receptor-2 antagonist CYN154806. The inhibitory effect of GLP
      1 on glucagon secretion was prevented by the PKA-inhibitor Rp-cAMPS and mimicked
      by the adenylate cyclase activator forskolin. Electrophysiological measurements
      revealed that GLP-1 decreased action potential height and depolarized interspike
      membrane potential. Mathematical modeling suggests both effects could result from
      inhibition of P/Q-type Ca2+ channels. In agreement with this, GLP-1 and omega
      agatoxin (a blocker of P/Q-type channels) inhibited glucagon secretion in islets
      depolarized by 70 mmol/L [K+ ]o , and these effects were not additive.
      Intracellular application of cAMP inhibited depolarization-evoked exocytosis in
      individual alpha-cells by a PKA-dependent (Rp-cAMPS-sensitive) mechanism. We
      propose that inhibition of glucagon secretion by GLP-1 involves activation of the
      few GLP-1 receptors present in the alpha-cell membrane. The resulting small
      elevation of cAMP leads to PKA-dependent inhibition of P/Q-type Ca2+ channels and
      suppression of glucagon exocytosis.

PMID- 30187656
TI  - Towards an individualized approach for predicting post-prostatectomy urinary
      incontinence: the role of nerve preservation and urethral stump length.

PMID- 30187657
TI  - NICE Guidance - Nivolumab for previously treated advanced renal cell carcinoma:
      (c) NICE (2017) Nivolumab for previously treated advanced renal cell carcinoma.

PMID- 30187654
TI  - Assessment of diastolic function and atrial remodeling by MRI - validation and
      correlation with echocardiography and filling pressure.
AB  - Atrial fibrosis can be estimated noninvasively by magnetic resonance imaging
      (MRI) using late gadolinium enhancement (LGE), but diastolic dysfunction is
      clinically assessed by transthoracic echocardiography (TTE), and rarely by MRI.
      This study aimed to evaluate well-established diastolic parameters using MRI, and
      validate them with TTE and left ventricular (LV) filling pressures, and to study
      the relationship between left atrial (LA) remodeling and parameters of diastolic
      function. The study retrospectively included 105 patients (53 +/- 16 years, 39
      females) who underwent 3D LGE MRI between 2012 and 2016. Medical charts were
      reviewed for the echocardiographic diastolic parameters E, A, and e' by TTE, and
      pressure catheterizations. E and A were measured from in-plane phase-contrast
      cardiac MRI images, and e' by feature-tracking, and validated with TTE.
      Interobserver and intraobserver variability was examined. Furthermore, LA
      volumes, function, and atrial LGE was correlated with diastolic parameters.
      Evaluation of e' in MRI had strong agreement with TTE (r = 0.75, P < 0.0001), and
      low interobserver and intraobserver variability. E and A by TTE showed strong
      agreement to MRI (r = 0.77, P = 0.001; r = 0.73, P = 0.003, for E and A,
      respectively). Agreement between E/e' by TTE and MRI was strong (r = 0.85, P =
      0.0004), and E/e' by TTE correlated moderately to invasive pressures (r = 0.59, P
      = 0.03). There was a strong relationship between LA LGE and pulmonary capillary
      wedge pressure (r = 0.81, P = 0.01). In conclusion, diastolic parameters can be
      measured with good reproducibility by cardiovascular MRI. LA LGE exhibited a
      strong relationship with pulmonary capillary wedge pressure, an indicator of
      diastolic function.

PMID- 30187658
TI  - New robots - cost, connectivity and artificial intelligence.

PMID- 30187659
TI  - Occupational exposure and risk of testicular cancer: what can an ecological study
      in the Nordic countries tell us?

PMID- 30187660
TI  - 2018: A Spacer Odyssey.

PMID- 30187661
TI  - Comment on: "Glucagon-like peptide-1 receptor expression in the human eye".

PMID- 30187662
TI  - Matrix metalloprotease 3 is associated with sarcopenia in rheumatoid arthritis -
      results from the CHIKARA study.
AB  - AIM: Patients with rheumatoid arthritis (RA) show lower muscle mass and a higher
      prevalence of sarcopenia than healthy individuals. Correlations between
      sarcopenia and disease activity, physical function, laboratory data and body
      composition at baseline were investigated in a prospective, observational study
      (CHIKARA study) of RA patients. METHODS: Body composition was measured using a
      bioelectrical impedance analyzer. Parameters were compared between sarcopenia and
      non-sarcopenia groups, and correlations between sarcopenia and Disease Activity
      Score of 28 joints - erythrocyte sedimentation rate (DAS28-ESR), modified health
      assessment questionnaire, treatment, and laboratory data, including matrix
      metalloproteinase 3 (MMP3), were investigated. RESULTS: The participants were 100
      patients with RA (women, 78%; mean age, 66.1 years). Mean disease duration was
      5.5 years, DAS28-ESR was 3.55 and the prevalence of sarcopenia was 28%. Median C
      reactive protein (CRP) and MMP3 were significantly higher in the sarcopenia group
      (0.21 mg/dL and 103.4 ng/mL) than in the non-sarcopenia group (0.11 mg/dL and
      70.3 ng/mL). Sarcopenia was negatively correlated with weight, body mass index
      (BMI), muscle mass, body fat mass, estimated bone mass and basal metabolic rate,
      and positively correlated with Steinbrocker stage, CRP and MMP3 on univariate
      analyses. BMI, body fat mass and MMP3 were independently associated with
      sarcopenia on multivariate logistic regression analysis. When MMP3 was >= 90.7
      ng/mL, the odds ratio for sarcopenia was increased 3.1-fold compared with < 90.7
      ng/mL (P = 0.018). CONCLUSION: The prevalence of sarcopenia was 28% in patients
      with RA whose disease activity was mild. Low BMI, high fat mass and high MMP3
      were independently associated with sarcopenia. MMP3 might be a useful marker for
      sarcopenia in patients with RA.

PMID- 30187664
TI  - Open-angle glaucoma and mortality: A long-term follow-up study.

PMID- 30187663
TI  - Voltage effects on muscarinic acetylcholine receptor-mediated contractions of
      airway smooth muscle.
AB  - Studies have shown that the activity of muscarinic receptors and their affinity
      to agonists are sensitive to membrane potential. It was reported that in airway
      smooth muscle (ASM) depolarization evoked by high K+ solution increases
      contractility through direct effects on M3 muscarinic receptors. In this study,
      we assessed the physiological relevance of voltage sensitivity of muscarinic
      receptors on ASM contractility. Our findings reveal that depolarization by high
      K+ solution induces contraction in intact mouse trachea predominantly through
      activation of acetylcholine release from embedded nerves, and to a lesser extent
      by direct effects on M3 receptors. We therefore devised a pharmacological
      approach to depolarize tissue to various extents in an organ bath preparation,
      and isolate contraction due exclusively to ASM muscarinic receptors within range
      of physiological voltages. Our results indicate that unliganded muscarinic
      receptors do not contribute to contraction regardless of voltage. Utilizing low
      K+ solution to hyperpolarize membrane potentials during contractions had no
      effect on liganded muscarinic receptor-evoked contractions, although it
      eliminated the contribution of voltage-gated calcium channels. However, we found
      that muscarinic signaling was potentiated by at least 42% at depolarizing
      voltages (average -12 mV) induced by high K+ solution (20 mmol/L K+ ). In
      summary, we conclude that contractions evoked by direct activation of muscarinic
      receptors have negligible sensitivity to physiological voltages. However,
      contraction activated by cholinergic stimulation can be potentiated by membrane
      potentials occurring beyond the physiological range of ASM.

PMID- 30187665
TI  - Hemi-macular detachment: EnFace optical coherence tomography characteristics and
      clinical implications.

PMID- 30187666
TI  - Effects on clinical outcomes of intensifying triple oral antidiabetic drug (OAD)
      therapy by initiating insulin versus enhancing OAD therapy in patients with type
      2 diabetes: A nationwide population-based, propensity-score-matched cohort study.
AB  - AIMS: To compare the effects of initiating insulin as a fourth-line antidiabetic
      therapy with the effects of enhancing oral antidiabetic drug (OAD) therapy in
      patients with type 2 diabetes mellitus (T2DM) with triple OAD therapy failure.
      MATERIALS AND METHODS: We conducted a nationwide population-based, retrospective
      cohort study involving 1022 (without prevalent diabetes-related complications
      [PDRCs]) and 2077 (with/without PDRCs) propensity score-matched pairs of fourth
      line insulin therapy users and enhanced OAD therapy users identified in the
      period 2004 to 2010. Clinical outcomes including a composite cardiovascular
      outcome (myocardial infarction, stroke, heart failure or ischaemic heart
      disease), peripheral vascular disease (PVD), hypoglycaemia and all-cause
      mortality were assessed up to 2013. Hypoglycaemia was adjusted in Cox models to
      consider its potential effect on study outcomes. RESULTS: In a T2DM cohort
      without PDRCs, fourth-line insulin therapy was not associated with greater risks
      of clinical outcomes, except hypoglycaemia (hazard ratio [HR] 1.45, 95%
      confidence interval [CI] 1.02-2.07), compared with enhanced OAD therapy. Among
      patients with T2DM with/without PDRCs, fourth-line insulin therapy was associated
      with greater risks of the composite cardiovascular outcome (HR 1.23, 95% CI 1.03
      1.46), heart failure (HR 1.59, 95% CI 1.12-2.25), ischaemic heart disease (HR
      1.37, 95% CI 1.09-1.73), PVD (HR 1.17, 95% CI 1.00-1.36), hypoglycaemia (HR 1.49,
      95% CI 1.20-1.85) and all-cause mortality (HR 1.48, 95% CI 1.01-2.17), but
      adjustment for hypoglycaemia significantly attenuated the risk of heart failure
      (HR 1.34, 95% CI 0.92-1.94), PVD (HR 1.15, 95% CI 0.98-1.34) and all-cause
      mortality (HR 1.30, 95% CI 0.84-1.99). CONCLUSIONS: Initiation of fourth-line
      insulin therapy can be considered for patients with T2DM with triple OAD therapy
      failure, and the importance of awareness and prevention of hypoglycaemia among
      insulin-treated patients with T2DM cannot be overstated.

PMID- 30187667
TI  - Long-term patient reported outcomes of elbow, wrist and hand surgery for
      rheumatoid arthritis.
AB  - AIM: A retrospective questionnaire survey was conducted to investigate the long
      term outcomes of elbow, wrist and hand surgery for rheumatoid arthritis (RA).
      METHODS: One hundred and thirteen RA patients underwent primary elective elbow,
      wrist or hand surgery at our hospital between January 2002 and December 2003. To
      evaluate the outcomes at 10 years after surgery, the patient-reported outcomes
      were assessed using an original questionnaire that inquired about the site of
      treatment; the modified Stanford Health Assessment Questionnaire (mHAQ) was also
      used. RESULTS: Responses were obtained from 67 patients (98 sites). In the 10
      years after surgery, the Disease Activity Score of 28 joint - erythrocyte
      sedimentation rate (4) and the modified Health Assessment Questionnaire scores of
      the patients showed significant improvement. Nearly 85% of patients were
      satisfied with the outcome at the surgical site. The most frequent reason for
      perceived improvement was 'pain relief' (all surgical sites). An 'improved
      appearance' was frequently reported after finger surgery and 'increased power'
      was frequently reported after wrist and thumb surgeries. With regard to elbow
      surgery, 30% of the patients were satisfied with the increase in motion and
      power. In contrast, approximately 20% of patients complained of decreased power
      around the surgical site after elbow and thumb surgeries. CONCLUSIONS: Our
      original patient-reported outcome assessment tool revealed that elbow, wrist and
      hand surgery provided long-lasting benefits in RA patients. While the efficacy
      differed in some of the surgical sites, pain relief was the most favorable
      effect. Altered medical therapy may also have impacted the patient-perceived
      outcomes of surgery at 10 years.

PMID- 30187668
TI  - Arthritis in sarcoidosis: A multicentric study from India.
AB  - INTRODUCTION: Ten to 15% of patients with sarcoidosis have associated arthritis.
      Chronic arthritis is fairly uncommon. There is a paucity of data on articular
      manifestations of the disease from India. METHODS: Case records of adult patients
      with sarcoidosis presenting to 11 rheumatology centers from 2005 to 2017 were
      retrospectively reviewed. Joint involvement was assessed clinically, classified
      as acute or chronic depending on duration of symptoms less or greater than 6
      months, respectively. RESULTS: A total of 117 patients with sarcoid arthritis
      were reviewed. Forty-five patients were classified as having Lofgren's syndrome.
      The pattern of joint involvement revealed the ankle to be most commonly affected
      in both the groups. Shoulder, wrist, metacarpophalangeal, proximal
      interphalangeal joints of hands and knee joint involvement were significantly
      more common in chronic sarcoid arthritis. Peripheral lymphadenopathy and uveitis
      were significantly more frequent in chronic sarcoid arthritis. Forty out of 49
      patients with acute arthritis followed up over a median of 1.8 years had achieved
      complete remission. Twelve out of 16 chronic sarcoid arthritis (median follow up
      2.5 years) had achieved complete remission with 15, 12 and five patients on
      steroids, methotrexate and hydroxychloroquine, respectively. One patient with
      acute sarcoid arthritis with concomitant interstitial lung disease had died due
      to lung infection. CONCLUSION: Acute oligoarthritis was the commonest
      presentation with the ankle being the most commonly affected joint. Upper limb
      joint (predominantly distal) and knee involvement were more common as reported in
      our largest series worldwide of chronic sarcoid arthritis in adults. Hilar
      adenopathy and erythema nodosum were common extra-articular features in both
      acute and chronic sarcoid arthritis. A limitation of the study was the
      retrospective nature of the analysis.

PMID- 30187669
TI  - Thoracoscopic resection of a cystic seminoma of the mediastinum.
AB  - Mediastinal seminoma is an uncommon tumor that accounts for 25% of primary
      mediastinal germ cell tumors, which in turn comprise fewer than 5% of all germ
      cell tumors. Although CT normally shows a solid, lobulated tumor, mediastinal
      cystic seminoma has rarely been described. Here, we report a 24-year-old man who
      presented with a mediastinal cystic tumor that was resected after an 18-month
      delay via video-assisted thoracoscopic surgery while in the supine position; the
      procedure involved lifting the chest wall with a subcutaneous Kirschner wire.
      Pathological examination revealed a mediastinal cystic seminoma. No evidence of
      recurrence has been noted during 25 months of follow-up. Mediastinal cystic
      seminoma should be considered in the differential diagnosis of cystic lesions of
      the mediastinum. Moreover, video-assisted thoracoscopic resection may be an
      appropriate option for the diagnosis and treatment of such lesions.

PMID- 30187670
TI  - Postoperative endophthalmitis following chandelier-assisted scleral buckle for
      primary repair of rhegmatogenous retinal detachment.

PMID- 30187672
TI  - The Curtius Rearrangement: Applications in Modern Drug Discovery and Medicinal
      Chemistry.
AB  - The Curtius rearrangement is the thermal decomposition of an acyl azide derived
      from carboxylic acid to produce an isocyanate as the initial product. The
      isocyanate can undergo further reactions to provide amines and their derivatives.
      Due to its tolerance for a large variety of functional groups and complete
      retention of stereochemistry during rearrangement, the Curtius rearrangement has
      been used in the synthesis of a wide variety of medicinal agents with amines and
      amine-derived functional groups such as ureas and urethanes. The current review
      outlines various applications of the Curtius rearrangement in drug discovery and
      medicinal chemistry. In particular, the review highlights some widely used
      rearrangement methods, syntheses of some key agents for popular drug targets and
      FDA-approved drugs. In addition, the review highlights applications of the
      Curtius rearrangement in continuous-flow protocols for the scale-up of active
      pharmaceutical ingredients.

PMID- 30187671
TI  - Heterotrimeric G-protein subunit Galphai2 contributes to agonist-sensitive
      apoptosis and degranulation in murine platelets.
AB  - Galphai2 , a heterotrimeric G-protein subunit, regulates various cell functions
      including ion channel activity, cell differentiation, proliferation and
      apoptosis. Platelet-expressed Galphai2 is decisive for the extent of tissue
      injury following ischemia/reperfusion. However, it is not known whether Galphai2
      plays a role in the regulation of platelet apoptosis, which is characterized by
      caspase activation, cell shrinkage and cell membrane scrambling with
      phosphatidylserine (PS) translocation to the platelet surface. Stimulators of
      platelet apoptosis include thrombin and collagen-related peptide (CoRP), which
      are further known to enhance degranulation and activation of alphaIIb beta3
      integrin and caspases. Using FACS analysis, we examined the impact of agonist
      treatment on activation and apoptosis in platelets drawn from mice lacking
      Galphai2 and their wild-type (WT) littermates. As a result, treatment with either
      thrombin (0.01 U/mL) or CoRP (2 MUg/mL or 5 MUg/mL) significantly upregulated PS
      exposure and significantly decreased forward scatter, reflecting cell size, in
      both genotypes. Exposure to CoRP triggered a significant increase in active
      caspase 3, ceramide formation, surface P-selectin, and alphaIIb beta3-integrin
      activation. These molecular alterations were significantly less pronounced in
      Galphai2 -deficient platelets as compared to WT platelets. In conclusion, our
      data highlight a previously unreported role of Galphai2 signaling in governing
      platelet activation and apoptosis.

PMID- 30187673
TI  - Downregulation of peroxisome proliferator-activated receptor gamma in the
      placenta correlates to hyperglycemia in offspring at young adulthood after
      exposure to gestational diabetes mellitus.
AB  - AIMS/INTRODUCTION: Children who are exposed to gestational diabetes mellitus
      (GDM) in utero are at high risk of developing related illnesses, such as type 2
      diabetes mellitus in young adulthood, but the underlying mechanism and related
      predictive biomarkers are not known. MATERIALS AND METHODS: The present study
      identified the related biomarkers of hyperglycemia in young adults from the
      relationship between fetal blood glucose and placental lipid transporters at
      messenger ribonucleic acid (mRNA) and protein expression levels. We recruited
      patients from a prospective cohort, and determined the mRNA and protein levels of
      placental fatty acid transporters. Diet-induced mouse models of GDM were
      established, and the mRNA and protein levels of the same transporters in
      placentas were validated. RESULTS: Only the mRNA levels of peroxisome
      proliferator-activated receptor gamma correlated with the levels of neonatal
      blood glucose in GDM patients using linear regression and Spearman's correlation
      analyses (r = 0.774, P = 0.001). The mRNA levels of peroxisome proliferator
      activated receptor gamma, matrix metalloproteinase-2 and fatty acid transport
      protein-6 correlated with blood glucose levels in mouse offspring (r = 0.82, P =
      0.001, r = 0.737, P = 0.006 and r = -0.891, P = 0.001, respectively) at young
      adulthood using the same analyses. Notably, we observed significantly higher
      blood glucose levels in GDM offspring at 12 weeks-of-age compared with the
      control and rosiglitazone-supplemented groups (P < 0.05). CONCLUSIONS: The
      downregulation of peroxisome proliferator-activated receptor gamma in the
      placenta might predict hyperglycemia in offspring at young adulthood.

PMID- 30187674
TI  - Mismatch between risk factors and preventive interventions? A register study of
      fall prevention among older people in one Swedish county.
AB  - BACKGROUND: Falls are a common and often a devastating health hazard for older
      people, causing suffering, morbidity and mortality. Falls are costly for society
      in terms of both resources and direct medical costs. Although knowledge about
      falls and fall prevention is well known, falls among older people are still a
      major problem. AIM AND OBJECTIVES: The aim was to estimate the prevalence of the
      risk of falls among older people receiving municipal health care. A further aim
      was to investigate the consistency between fall risk factors and preventive
      nursing interventions. DESIGN: A cross-sectional register study. METHODS: Data
      containing risk assessments based on the Downton Fall Risk Index (DFRI) and
      planned interventions by the municipal health care were collected from the
      Swedish national quality registry, Senior Alert. Data were analysed using
      descriptive and analytic statistics. RESULTS: In the sample of 5,427 older
      people, the prevalence of the risk of falling was 79%. There was a difference in
      prevalence between the different types of municipal health care, sex and age. The
      most common preventive intervention was environment adjustments, and the least
      planned intervention was information/education about falls. Physical activity as
      an intervention was planned among 13.2% of the participants. Approximately 27% of
      the older people did not have any planned interventions despite being at risk of
      falling. Planned interventions did not always correspond with the risk factors;
      for instance, only 35.4% of those at risk of falling due to medication obtained
      pharmaceutical reviews as a preventive measure to decrease the risk. CONCLUSION:
      The risk of falling is common among older people, and the preventive
      interventions do not sufficiently follow current evidence. This implies that
      systematic implementation of fall-prevention guidelines is needed in municipal
      care. IMPLICATION FOR PRACTICE: A better match between identified risk factors
      and preventive interventions is warranted.

PMID- 30187677
TI  - In this Issue: Volume 109, Issue 9, September 2018.

PMID- 30187675
TI  - Clinical practice guidance for next-generation sequencing in cancer diagnosis and
      treatment (Edition 1.0).
AB  - In Japan, the social (medical) health-care system is on the way to being
      developed to advance personalized medicine through the implementation of cancer
      genomic medicine, known as "cancer clinical sequencing," which uses a next
      generation sequencer. However, no Japanese guidance for cancer genomic testing
      exists. Gene panel testing can be carried out to help determine patient
      treatment, confirm diagnosis, and evaluate prognostic predictions of patients
      with mainly solid cancers for whom no standard treatment is available. This
      guidance describes how to utilize gene panel testing according to the type of
      cancer: childhood cancer, rare cancer, carcinoma of unknown primary, and other
      cancers. The level of evidence classification for unified use in Japan is also
      detailed. This guidance establishes the basic principles of the quality control
      of specimens, requirements of medical institutions, informed consent, handling of
      data during the postanalysis stage, and treatment options based on the evidence
      level. In Japan, gene panel testing for cancer treatment and diagnosis is
      recommended to comply with this guidance. This is a collaborative work of the
      Japanese Society of Medical Oncology, Japan Society of Clinical Oncology, and the
      Japanese Cancer Association.

PMID- 30187676
TI  - PD-1+ TIM-3+ T cells in malignant ascites predict prognosis of gastrointestinal
      cancer.
AB  - The liquid biopsy of ascites fluid could be an excellent source of tumor and
      microenvironment for the study of prognostic biomarkers because of its
      accessibility. Tumor-infiltrating lymphocytes (TILs) can predict prognosis in
      multiple malignancies, including the response to immune checkpoint inhibitors, a
      breakthrough cancer therapy. However, TILs' profiles from malignant ascites have
      not been extensively studied. Using flow cytometric analysis, we quantified the
      proportion of exhausted T cells and memory/naive/effector T-cell subsets, among
      the CD4+ and CD8+ T-cell populations of paired TILs and peripheral blood T cell
      samples (n = 22). The correlation between CD4+ and CD8+ subset profiles suggested
      that the combined analysis of CD4+ and CD8+ cells in malignant ascites was
      clinically significant. We found that cells positive for the exhaustion markers
      programmed cell death-1 (PD-1), and T-cell immunoglobulin and mucin domain 3 (TIM
      3), and cells coexpressing PD-1 and TIM-3 abundantly exist among malignant
      ascites TILs. Furthermore, patients with high frequency of PD-1+ TIM-3+ cells
      among the CD4+ and CD8+ T-cell population showed worse clinical outcome in
      multivariate analysis (n = 27). We propose that exhausted ascites TILs represent
      a clinically significant prognostic biomarker in advanced gastrointestinal cancer
      and represent an important target for immune checkpoint inhibitors.

PMID- 30187679
TI  - Is sonoelastography a helpful method of evaluation to diagnose Sjogren's
      syndrome?
AB  - OBJECTIVE: A new sonoelastography technique - virtual touch tissue quantification
      of acoustic radiation force impulses (ARFI) - offers a promising method for
      measuring tissue rigidity. The aim of this study was to assess the usefulness of
      ARFI for diagnosing Sjogren's syndrome (SS). METHODS: This transversal
      prospective study included 41 patients with SS according to American-European
      Consensus Group (AECG) criteria, and a control group without symptoms. All
      subjects underwent ARFI high-resolution ultrasound assessment of the parotid
      glands (PG) and submandibular glands (SMG). RESULTS: In patients with SS, parotid
      gland shear wave velocity (SWV) was 2.08 m/s +/- 0.55, significantly higher than
      in control subjects (1.2 m/s +/- 0.17) (P = 0.0001); submandibular gland SWV was
      higher in SS patients (2.12 m/s +/- 0.44) than control subjects (1.56 m/s +/-
      0.16) (P = 0.001). CONCLUSIONS: Acoustic radiation force impulses
      sonoelastography can assist diagnosis of SS, and is a non-invasive and fast
      method of detecting pathological changes to the parotid and submandibular glands.

PMID- 30187680
TI  - Conbercept for treatment of choroidal neovascularization secondary to pathologic
      myopia.

PMID- 30187678
TI  - Predictors and interdependence of family support in a random sample of long-term
      young breast cancer survivors and their biological relatives.
AB  - OBJECTIVE: Women diagnosed with breast cancer younger than 45 years (young breast
      cancer survivors-YBCS) and their biological relatives face significant stressors.
      Although family support is an important coping resource, little is known about
      YBCS' and relatives' support and whether it is interdependent. The study
      described family support in YBCS and their biological relatives; identified
      demographic, clinical, and psychosocial predictors of support; and determined the
      interdependence of support in YBCS-relatives family units. METHODS: Data were
      collected from a random sample of YBCS and their first- or second-degree female
      relatives. Actor-partner interdependence models (APIM) explored predictors and
      interdependence of YBCS' and relatives' family support in dyads (YBCS and
      relative) and triads (YBCS and two relatives). RESULTS: Among n = 310 YBCS and n
      = 431 first- or second-degree relatives, family support was higher in triads
      compared to dyads. APIMs identified actor effects in dyads, and actor and partner
      effects in triads. Across all family units, YBCS' higher self-efficacy was
      associated with higher YBCS support (actor effect) and relative support (partner
      effect); YBCS' prior diagnosis of depression was associated with lower YBCS and
      relative support (actor and partner effect); cost-related lack of access to care
      was associated with lower support among YBCS (actor effect) and relatives (actor
      and partner effect). CONCLUSIONS: Family support was interdependent and was
      affected by self-efficacy, depression, and access to care. Interventions should
      include YBCS and relatives, enhance self-efficacy and access to care.

PMID- 30187681
TI  - Protein modeling and clinical description of a novel in-frame GLB1 deletion
      causing GM1 gangliosidosis type II.
AB  - BACKGROUND: Beta-galactosidase-1 (GLB1) is a lysosomal hydrolase that is
      responsible for breaking down specific glycoconjugates, particularly GM1
      (monosialotetrahexosylganglioside). Pathogenic variants in GLB1 cause two
      different lysosomal storage disorders: GM1 gangliosidosis and
      mucopolysaccharidosis type IVB. In GM1 gangliosidosis, decreased beta
      galactosidase-1 enzymatic activity leads to the accumulation of GM1 gangliosides,
      predominantly within the CNS. We present a 22-month-old proband with GM1
      gangliosidosis type II (late-infantile form) in whom a novel homozygous in-frame
      deletion (c.1468_1470delAAC, p.Asn490del) in GLB1 was detected. METHODS: We used
      an experimental protein structure of beta-galactosidase-1 to generate a model of
      the p.Asn490del mutant and performed molecular dynamic simulations to determine
      whether this mutation leads to altered ligand positioning compared to the wild
      type protein. In addition, residual mutant enzyme activity in patient leukocytes
      was evaluated using a fluorometric assay. RESULTS: Molecular dynamics simulations
      showed the deletion to alter the catalytic site leading to misalignment of the
      catalytic residues and loss of collective motion within the model. We predict
      this misalignment will lead to impaired catalysis of beta-galactosidase-1
      substrates. Enzyme assays confirmed diminished GLB1 enzymatic activity (~3% of
      normal activity) in the proband. CONCLUSIONS: We have described a novel,
      pathogenic in-frame deletion of GLB1 in a patient with GM1 gangliosidosis type
      II.

PMID- 30187682
TI  - Factors potentially linked with the occurrence of antimicrobial resistance in
      selected bacteria from cattle, chickens and pigs: A scoping review of
      publications for use in modelling of antimicrobial resistance (IAM.AMR Project).
AB  - Antimicrobial resistance is a complex issue with a large volume of published
      literature, and there is a need for synthesis of primary studies for an
      integrated understanding of this topic. Our research team aimed to have a more
      complete understanding of antimicrobial resistance in Canada (IAM.AMR Project)
      using multiple methods including the literature reviews and quantitative
      modelling. To accomplish this goal, qualitative features of publications (e.g.,
      geographical location, study population) describing potential relationships
      between the occurrence of antimicrobial resistance and factors (e.g.,
      antimicrobial use; management system) were of particular interest. The objectives
      of this review were to (a) describe the available peer-reviewed literature
      reporting potential relationships between factors and antimicrobial resistance;
      and (b) to highlight data gaps. A comprehensive literature search and screening
      were performed to identify studies investigating factors potentially linked with
      antimicrobial resistance in Campylobacter species, Escherichia coli and
      Salmonella enterica along the farm-to-fork pathway (farm, abattoir (slaughter
      houses) and retail meats) for the major Canadian livestock species (beef cattle,
      broiler chicken and pigs). The literature search returned 14,966 potentially
      relevant titles and abstracts. Following screening of titles, abstracts and full
      text articles, the qualitative features of retained studies (n = 28) were
      extracted. The most common factors identified were antimicrobial use (n = 13
      studies) and type of farm management system (e.g., antibiotic-free, organic; n =
      8). Most studies were conducted outside of Canada and involved investigations at
      the farm level. Identified data gaps included the effect of vaccination, industry
      specific factors (e.g., livestock density) and factors at sites other than farm
      along the agri-food chain. Further investigation of these factors and other
      relevant industry activities are needed for the development of quantitative
      models that aim to identify effective interventions to mitigate the occurrence of
      antimicrobial resistance along the agri-food chain.

PMID- 30187683
TI  - Risk factors associated with histological upgrade of gastric low-grade dysplasia
      on pretreatment biopsy.
AB  - OBJECTIVES: Histological discrepancies between biopsy and resection specimens are
      common. In this study, we aimed to analyze the risk factors predicting
      histological upgrade or downgrade of biopsy-diagnosed gastric low-grade dysplasia
      (LGD). METHODS: The medical records of patients with 104 biopsy-diagnosed gastric
      LGD from January 2011 to December 2017 were collected. The association of
      endoscopic characteristics with histological discrepancies between the biopsy and
      resection specimens was analyzed. The risk factors for histological upgrade were
      studied using the multivariate analysis. RESULTS: Among the 104 lesions, 88 were
      removed by endoscopic resection and 16 were monitored. The upgrade and downgrade
      rates of the pathological diagnosis were 48.9% and 12.5%, respectively. Lesion
      size >20 mm, surface redness and positive results in magnifying endoscopy with
      narrow band imaging (ME-NBI) were risk factors for histological upgrade. Compared
      with the negative ME-NBI group, the positive ME-NBI group had a higher upgrade
      rate (56.8% vs 7.1%) but a lower downgrade rate (2.7% vs 64.3%). In addition, 11
      of the 16 the gastric LGD with negative ME-NBI findings were monitored, and all
      11 lesions regressed to gastritis during follow-up. CONCLUSIONS: Endoscopic
      resection should be recommended in cases of LGD showing surface redness, with a
      lesion size of >20 mm or positive ME-NBI result, whereas regular follow-up may be
      an option for LGD with negative ME-NBI result.

PMID- 30187685
TI  - Identification of the novel HLA allele, HLA-B*40:06:07, by sequence-based typing.
AB  - HLA-B*40:06:07 has one synonymous nucleotide change from HLA-B*40:06:01:01 at
      nucleotide 81 (codon 3 histidine).

PMID- 30187684
TI  - Physical fitness, hormonal, and immunological responses during prolonged military
      field training.
AB  - Physical fitness is crucial to warfighters' performance in the battlefield.
      Previous studies have shown negative changes in their hormonal and neuromuscular
      responses induced by military field training (MFT). The purpose of this study was
      to investigate the changes in hormonal and immunological values and body
      composition during a prolonged MFT and to find out how warfighters' physical
      condition influences these changes. Conscripts (n = 49, age 20 +/- 1 years,
      height 179 +/- 9 cm, body mass 73.8 +/- 7.8 kg, fat 12.6 +/- 3.7% and BMI 23
      kg/m2) were measured before, during, after MFT, and after a 4-day recovery
      period. Serum insulin-like growth factor-1 (IGF-1), tumor necrosis factor alpha
      (TNF-alpha), interleukin-6 (IL-6) concentrations, creatine kinase (CK) activity
      and leptin concentration were analyzed as well as body composition throughout
      MFT. Neuromuscular performance was assessed via lower and upper body muscle
      endurance at the beginning of the study. During MFT, there was a significant
      decrease (P < 0.05) in body mass (2.3%), fat mass (7.7%) and in muscle mass
      (2.2%), but all of these values recovered to PRE-levels after the recovery
      period. Serum IGF-1 (22%) and leptin decreased (66%) while CK increased (88%)
      significantly (P < 0.05) during MFT but recovered at the end of MFT. Upper body
      dynamic and trunk isometric muscular endurance had a positive correlation (r =
      0.37. P < 0.05) with the change in IGF-1 during MFT and a negative correlation
      with the changes in CK (-0.34, P < 0.05). The results show that there were
      negative changes in conscript's body composition and hormonal and immunological
      values during the prolonged MFT. These changes suggest that the physiological
      stress was high during MFT. High levels of upper body and trunk muscular strength
      were negatively correlated with warfighters' physiological effects and should
      therefore be developed prior to actual deployment to reduce the physical decline
      experienced during prolonged MFTs.

PMID- 30187686
TI  - Radiologic features in symptomatic/asymptomatic heels of patients with ankylosing
      spondylitis.
AB  - AIM: Most heel pain occurs at the posterior or plantar aspect, where main
      entheses of the heel are located. However, simple radiographs as basic work-up
      tools, their features based on their association with local symptoms in the heel
      in ankylosing spondylitis (AS) patients, have rarely been described. METHOD:
      Forty patients with AS and unilateral heel pain were enrolled to evaluate
      radiographic differences between symptomatic and asymptomatic heels. The two
      groups were assessed according to symptom location: posterior (group PS) or
      plantar (group PL). Typical abnormalities in bone and/or soft tissue on the heel
      due to inflammation were compared. RESULTS: In group PS (20 cases), 19 (95%)
      symptomatic feet and 7 (35%) asymptomatic feet showed abnormal findings on the
      posterior heel and symptomatic feet showed 6 (30%) plantar abnormalities. Erosion
      of the posterior calcaneal tuberosity, obliteration of the retrocalcaneal recess
      (RR), and swelling shadows with increased thickness on posterior soft tissue were
      observed more frequently and significantly in symptomatic feet in group PS (P <
      0.05). In group PL (20 cases), 11 (55%) symptomatic feet and 8 (40%) asymptomatic
      feet showed abnormalities on the plantar heel and symptomatic feet showed 14
      (70%) posterior abnormalities, and none showed significant differences between
      symptomatic and asymptomatic feet. CONCLUSION: Among simple radiographic
      alterations on heels with AS, such changes around the enthesis of the Achilles as
      bony erosion and RR obliteration with swollen posterior soft tissue are strongly
      related to current painful posterior heels. Assessment of enthesitis of the
      Achilles tendon in AS using plain radiography seems to be valid.

PMID- 30187687
TI  - Diurnal rhythms of heart and respiratory rates in donkeys of different age groups
      during the cold-dry and hot-dry seasons in a tropical savannah.
AB  - The aim of this study was to determine the effect of season on diurnal rhythms of
      heart (HR) and respiratory rates (RespR) in the adult, yearling, and foal donkeys
      during the cold-dry and hot-dry seasons under natural light/dark cycle. The
      resting HR and RespR were recorded bihourly for 24 consecutive hours from 06:00
      to 06:00 h (GMT +1) in 30, clinically healthy donkeys (10 adults,10 yearlings,
      and 10 foals). Dry-bulb temperature (DBT), relative humidity (RH), temperature
      humidity index (THI) and wet-bulb globe temperature index (WBGT) inside the pen
      were recorded bihourly from 06:00 to 06:00 h. Values of DBT, THI, and WBGT
      obtained during the hot-dry season were significantly (P < 0.05) higher than
      corresponding values recorded during the cold-dry season. Application of single
      cosinor procedure showed that HR and RespR exhibited daily rhythmicity in both
      seasons. The mesors of the HR in adult (41.51 +/- 0.34 beats/min [bpm]), yearling
      (40.80 +/- 0.43 bpm), and foal (47.55 +/- 0.40 bpm) donkeys during the cold-dry
      season were significantly (P < 0.01) lower, compared to the corresponding values
      of 48.4 +/- 0.40 bpm, 50.42 +/- 0.52 bpm and 58.10 +/- 0.50 bpm, respectively
      during the hot-dry season. The mesors of RespR in adult, yearling, and foal
      donkeys during the hot-dry season were higher (P < 0.05), when compared to the
      corresponding values recorded in the cold-dry season. The HR and RespR of foals
      were significantly (P < 0.05) higher than those of the adult and yearling
      donkeys. Amplitudes of HR and RespR were higher during the hot-dry season than
      the cold-dry season. In conclusion, seasonal changes affect diurnal rhythmicity
      of HR and RespR of adult, yearling, and foal donkeys during the cold-dry and hot
      dry seasons. The HR and RespR of donkeys vary with age, with higher values in the
      foals than the adult and yearling donkeys in both seasons.

PMID- 30187688
TI  - A multicentre observational study comparing patient reported outcomes to assess
      reliability of swollen and tender joint assessments and response to certolizumab
      treatment as compared to clinician assessments in rheumatoid arthritis.
AB  - AIMS: The use of swollen (SJC) and tender joint counts (TJC) for rheumatoid
      arthritis (RA) disease activity and treatment effectiveness is well established.
      Patient-reported outcomes (PRO) are important. However, it is unknown if patient
      scoring is as reliable as that of trained professionals. METHODS: PRO including
      SJC and TJC were assessed at baseline, 6 and 12 weeks by patients and clinicians.
      Data were collected using ePRO (electronic) and pPRO (paper). The Least Squares
      Method (LSM), Pearson correlation (Rs) and weighted Kappa scores were used to
      assess inter-rater reliability and agreement of responses between the patient,
      nurse and physician for changes in TJC and SJC from 0 to 12 weeks of treatment.
      RESULTS: There was a total of 341 evaluable matched joint assessment in 52
      patients with RA: 157 nurse, 106 patient and 78 physician. There were matched
      joint count pairs for 104 patient-nurse, 72 physician-nurse and 21 patient
      physician. Correlation (R) of TJC scores were as follows: patient-nurse 0.83 (P <
      0.001), physician-nurse 0.85 (P < 0.001) and physician-patient 0.59 (P = 0.005).
      The inter-rater reliability (agreement) of the patient-nurse pairs had a weighted
      Kappa of 0.59 (0.53, 0.68). Correlation (R) of SJC scores were as follows:
      patient-nurse 0.69 (P < 0.001), physician-nurse 0.66 (P < 0.001) and physician
      patient 0.42 (P = 0.058). The inter-rater reliability (agreement) of the patient
      nurse pairs had a weighted Kappa of 0.48 (0.41, 0.55). CONCLUSIONS: There is a
      moderate to high level of agreement between clinicians and patient TJC and SJC
      assessments that suggest it may be a useful option in assessing joints and
      response in RA. Further evaluation of RA activity tools such as Disease Activity
      Score of 28 joints, Crohn Disease Activity Index or Simple Disease Activity Index
      utilizing patient assessments may be worth exploring.

PMID- 30187690
TI  - Non-native species led to marked shifts in functional diversity of the world
      freshwater fish faunas.
AB  - Global spread of non-native species profoundly changed the world biodiversity
      patterns, but how it translates into functional changes remains unanswered at the
      world scale. We here show that while in two centuries the number of fish species
      per river increased on average by 15% in 1569 basins worldwide, the diversity of
      their functional attributes (i.e. functional richness) increased on average by
      150%. The inflation of functional richness was paired with changes in the
      functional structure of assemblages, with shifts of species position toward the
      border of the functional space of assemblages (i.e. increased functional
      divergence). Non-native species moreover caused shifts in functional identity
      toward higher body sized and less elongated species for most of assemblages
      throughout the world. Although varying between rivers and biogeographic realms,
      such changes in the different facets of functional diversity might still increase
      in the future through increasing species invasion and may further modify
      ecosystem functioning.

PMID- 30187689
TI  - Prophylactic air-extraction strategy after thoracoscopic wedge resection.
AB  - BACKGROUND: Since the conception of enhanced recovery after surgery protocols,
      tubeless strategies have become popular. Herein, we introduce a previously
      unreported alternative air-extraction strategy for patients who have undergone
      thoracoscopic wedge resection and explore its feasibility and safety. METHODS:
      Between January 2015 and June 2017, 264 consecutive patients underwent
      thoracoscopic wedge resection with different drainage strategies. Patients were
      divided according to the postoperative drainage strategies used: routine chest
      tube drainage (RT group), complete omission of chest tube drainage (OT group),
      and prophylactic air-extraction catheter insertion procedure (PC group). Using
      the propensity score matching method, clinical parameters and objective operative
      qualities were compared among the three groups. RESULTS: Optimal 1:1 matching was
      used to form pairs of RT (n =36) and PC (n =36) groups and balance baseline
      characteristics among the three groups. The incidence rates of pneumothorax were
      5.6% (2/36), 9.8% (5/51), and 19.4% (7/36) in the RT, OT, and PC groups,
      respectively (P = 0.07). Chest tube reinsertion incidence for postoperative
      pneumothorax was 19.4% (1/7) in the PC group and 60% (3/5) in the OT group. Other
      postoperative complications were comparable among these groups. CONCLUSIONS: The
      prophylactic air-extraction strategy may be an alternative procedure for selected
      patients. Remedial air extraction may reduce the occurrence of chest tube
      reinsertion for pneumothorax patients, but further investigation is required.

PMID- 30187691
TI  - Hyperspectral scanning laser optical tomography.
AB  - In order to study physical relationships within tissue volumes or even organism
      level systems, the spatial distribution of multiple fluorescent markers needs to
      be resolved efficiently in three-dimensions. Here, rather than acquiring discrete
      spectral images sequentially using multiple emission filters, a hyperspectral
      scanning laser optical tomography (SLOT) system is developed to obtain
      hyperspectral volumetric data sets with 2 nm spectral resolution of optically
      transparent mesoscopic (mm-cm) specimens. This is achieved by acquiring a series
      of point-scanning hyperspectral extended depth of field images at different
      angles and subsequently tomographically reconstructing the 3D intensity
      distribution for each wavelength. This technique is demonstrated to provide
      robust measurements via the comparison of spectral and intensity profiles of
      fluorescent bead phantoms. Due to its enhanced spectral resolving ability, this
      technique is also demonstrated to resolve largely overlapping fluorophores, as
      demonstrated by the 3D fluorescence hyperspectral reconstruction of a dual
      labelled mouse thymus gland sample and the ability to distinguish tumorous and
      normal tissues of an unlabeled mouse intestine sample. This article is protected
      by copyright. All rights reserved.

PMID- 30187692
TI  - ACE inhibition for severe bronchopulmonary dysplasia - an approach based on
      physiology.
AB  - Premature infants have a high incidence of bronchopulmonary dysplasia (BPD).
      Systemic hypertension, arterial thickness and stiffness, and increased systemic
      afterload may all contribute to BPD pathophysiology by altering left ventricular
      (LV) function and increasing pulmonary venous congestion by lowering end
      diastolic compliance. This case series studied the usefulness of angiotensin
      converting enzyme (ACE) inhibition by measuring clinical and echocardiographic
      improvements in six consecutive infants with "severe" BPD unresponsive to
      conventional therapy. The range of gestation and birthweight were 23-29 weeks and
      505-814 g, respectively. All required mechanical ventilation (including high
      frequency oscillation) and all but one were administered postnatal
      corticosteroids. Other treatments including sildenafil and diuretics made no
      clinical improvements. Captopril was started for systemic hypertension after
      cardiac and vascular ultrasounds which were repeated 5 weeks later. A significant
      reduction in oxygen (55 +/- 25 to 29 +/- 3%, two-tailed P = 0.03) and ventilator
      requirements, and improved cardiovascular parameters were noted. This included a
      trend toward reduction in aorta intima media thickness [840 +/- 94 to 740 +/- 83
      MUm, P = 0.07] and an increased pulsatile diameter [36 +/- 14 to 63 +/- 25 MUm, P
      = 0.04]). Improvements were observed for both systolic (increased LV output, 188
      +/- 13 to 208 +/- 13 mL/kg/min, P = 0.046 and mean velocity of circumferential
      fiber shortening, 1.6 +/- 0.2 to 2.5 +/- 0.3 [circ/sec], P = 0.0004) and
      diastolic (decreased isovolumic relaxation time, 69.6 +/- 8.2 to 59.4 +/- 5 msec,
      P = 0.044) function which was accompanied by increased pulmonary vein flow. Right
      ventricular output increased accompanied by a significant lowering of pulmonary
      vascular resistance. These findings suggest that improving respiratory and
      cardiac indices (especially diastolic function) warrants further exploration of
      ACE inhibition in BPD infants unresponsive to conventional therapy.

PMID- 30187694
TI  - Thymus autonomy as a prelude to leukemia.
AB  - Cell competition in the thymus promotes turnover and functions as a tumor
      suppressor by inhibiting leukemia. Using thymus transplantation experiments, we
      have shown that the presence of T lymphocyte precursors, recently seeding the
      thymus, promotes the clearance of precursors with a longer time of thymus
      residency. If cell competition is impaired and no cells seed the thymus, the
      organ is capable of sustaining T lymphocyte production, a state termed thymus
      autonomy. However, we observed consistently that prolonged autonomy is permissive
      to the emergence of T cell acute lymphoblastic leukemia (T-ALL). This resembled
      the onset of T-ALL in patients treated by gene therapy for X-linked severe
      combined immunodeficiency (SCID-X1). Following treatment, thymus activity was
      established, with T lymphocyte production, although no bone marrow contribution
      was detected. However, some patients developed T-ALL. The favored explanation for
      malignant transformation was considered to be genotoxicity due to integration of
      the retroviral vector next to oncogenes, thereby activating them ectopically.
      Although plausible, we consider an alternative, mutually nonexclusive
      explanation: that any condition enabling prolonged thymus autonomy will promote
      leukemogenesis. In support of this view, two independent studies have recently
      shown that the efficacy of reconstitution of the bone marrow in the context of
      SCID-X1 dramatically influences the outcome of treatment, and that lymphoid
      malignancies emerge following transplantation of a small number of healthy
      progenitors. Here, we discuss the most recent data in light of our own studies in
      thymopoiesis and the conditions that trigger malignant transformation of
      thymocytes in various experimental and clinical settings.

PMID- 30187695
TI  - Aerobic exercise for axial spondyloarthritis - its effects on disease activity
      and function as compared to standard physiotherapy: A systematic review and meta
      analysis.
AB  - AIM: To evaluate the impact of an aerobic fitness program on disease activity,
      defined by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and on
      C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and the Bath
      Ankylosing Spondylitis Functional Index (BASFI) in case of axial
      spondyloarthritis. METHODS: A systematic review of the literature, following the
      Prisma recommendations, was performed by two reviewers on the PubMed and Embase
      databases. Controlled trials assessing the efficacy of aerobic exercises compared
      to physiotherapy on axial spondyloarthritis disease activity were included. The
      diagnosis of axial spondyloarthritis was meeting the New York criteria and/or the
      Assessment in Axial Spondyloarthritis International Working Group criteria.
      Aerobic fitness was defined as an exercise performed at 50%-90% of the maximal
      heart rate or between 50% and 80% oxygen consumption (VO2 ) peak. RESULTS: Five
      hundred and twenty abstracts were identified and 93 abstracts were analyzed.
      Eight studies met the selection criteria and 6 were finally included in this
      study because of the presence of a control group. Both groups were similar in
      terms of age, sex ratio, disease duration. Aerobic exercise provided a positive
      impact on the BASDAI in the intervention group (148 patients) (weighted mean
      difference [WMD]: -0.52 [95% CI: -0.9 to -0.13]) (I2 : 10.3%, P = 0.35). However,
      when compared to a control group (152 patients), the improvement of BASDAI didn't
      reach significance (WMD: -0.25 [95% CI: -0.83 to 0.32]) (I2 : 0%, P = 0.41).
      Aerobic exercise did not improve BASFI, CRP or ESR. CONCLUSION: Aerobic exercise
      did not provide beneficial effects either on disease activity or on physical
      function and biological parameters when compared to a control group in axial
      spondyloarthritis.

PMID- 30187696
TI  - In Bae Yoon, an Inventor and Pioneer in Laparoscopic Surgery.

PMID- 30187693
TI  - The Smell of Hypoxia: using an electronic nose at altitude and proof of concept
      of its role in the prediction and diagnosis of acute mountain sickness.
AB  - Electronic nose (e-nose) devices may be used to identify volatile organic
      compounds (VOCs) in exhaled breath. VOCs generated via metabolic processes are
      candidate biomarkers of (patho)physiological pathways. We explored the
      feasibility of using an e-nose to generate human "breathprints" at high altitude.
      Furthermore, we explored the hypothesis that pathophysiological processes
      involved in the development of acute mountain sickness (AMS) would manifest as
      altered VOC profiles. Breath analysis was performed on Sherpa and lowlander
      trekkers at high altitude (3500 m). The Lake Louise Scoring (LLS) system was used
      to diagnose AMS. Raw data were reduced by principal component (PC) analysis
      (PCA). Cross validated linear discriminant analysis (CV-LDA) and receiver
      operating characteristic area under curve (ROC-AUC) assessed discriminative
      function. Breathprints suitable for analysis were obtained from 58% (37/64) of
      samples. PCA showed significant differences between breathprints from
      participants with, and without, AMS; CV-LDA showed correct classification of
      83.8%, ROC-AUC 0.86; PC 1 correlated with AMS severity. There were significant
      differences between breathprints of participants who remained AMS negative and
      those whom later developed AMS (CV-LDA 68.8%, ROC-AUC 0.76). PCA demonstrated
      discrimination between Sherpas and lowlanders (CV-LDA 89.2%, ROC-AUC 0.936). This
      study demonstrated the feasibility of breath analysis for VOCs using an e-nose at
      high altitude. Furthermore, it provided proof-of-concept data supporting e-nose
      utility as an objective tool in the prediction and diagnosis of AMS. E-nose
      technology may have substantial utility both in altitude medicine and under other
      circumstances where (mal)adaptation to hypoxia may be important (e.g., critically
      ill patients).

PMID- 30187698
TI  - Socioeconomic Inequalities in Stomach Cancer Screening in Korea, 2005-2015: After
      the Introduction of the National Cancer Screening Program.
AB  - PURPOSE: This study aimed to investigate socioeconomic inequalities in stomach
      cancer screening in Korea and trends therein across income and education groups.
      MATERIALS AND METHODS: Data from the Korean National Cancer Screening Survey, a
      nationwide cross-sectional survey, were utilized. A total of 28913 men and women
      aged 40 to 74 years were included for analysis. Prior experience with stomach
      cancer screening was defined as having undergone either an endoscopy or
      gastrointestinal series within the past two years. The slope index of inequality
      (SII) and relative index of inequality (RII) were evaluated to check
      inequalities. RESULTS: Stomach cancer screening rates increased from 40.0% in
      2005 to 74.8% in 2015, with an annual percent change of 5.8% [95% confidence
      interval (CI) 4.2 to 7.5]. Increases in stomach cancer screening rates were
      observed for all age, education, and household income groups. Inequalities in
      stomach cancer screening were noted among individuals of differing levels of
      education, with a pooled SII estimate of 6.14% (95% CI, 3.94 to 8.34) and RII of
      1.26 (95% CI, 1.12 to 1.40). Also, income-related inequalities were observed with
      an SII of 6.93% (95% CI, 4.89 to 8.97) and RII of 1.30 (95% CI, 1.17 to 1.43).
      The magnitude of inequality was larger for income than for education. CONCLUSION:
      Both education and income-related inequalities were found in stomach cancer
      screening, despite a continuous increase in screening rate over the study period.
      Income-related inequality was greater than education-related inequality, and this
      was more apparent in women than in men.

PMID- 30187699
TI  - Outcomes of Non-High Grade Serous Carcinoma after Neoadjuvant Chemotherapy for
      Advanced-Stage Ovarian Cancer: Single-Institution Experience.
AB  - PURPOSE: Outcomes in patients with ovarian high-grade serous carcinoma (HGSC)
      treated with neoadjuvant chemotherapy (NAC) have been widely studied; however,
      there is limited information on responses to chemotherapy among patients with non
      HGSC. The aim of this study was to compare the survival outcomes of patients with
      advanced-stage non-HGSC and HGSC treated with NAC. MATERIALS AND METHODS: This
      study was a retrospective analysis of patients with advanced-stage ovarian cancer
      treated at Yonsei Cancer Hospital between 2006 and 2017. The demographics,
      chemotherapy response, and survival rates were compared between patients with non
      HGSC and those with HGSC. RESULTS: Among 220 patients who underwent NAC, 25
      (11.4%) patients had non-HGSC histologic subtypes, and all received a taxane
      platinum combination regimen for NAC. Patients with non-HGSC had lower baseline
      cancer antigen-125 levels (p<0.001), poorer response rates (p<0.001), lower rates
      of optimal cytoreduction (p=0.003), and poorer progression-free survival (PFS)
      (median PFS 10.3 months vs. 18.3 months; p=0.009) and overall survival (OS)
      (median OS 25.5 months vs. 60.6 months; p<0.001), compared to those with HGSC. In
      multivariate analysis, non-HGSC was a negative prognostic factor for both PFS
      [hazard ratio (HR), 3.19; 95% confidence interval (CI), 1.73-5.88] and OS (HR,
      4.22; 95% CI, 2.07-8.58). CONCLUSION: In this study, poorer survival outcomes
      were observed in patients who underwent NAC for treatment of non-HGSC versus
      those treated for HGSC. Different treatment strategies are urgently required to
      improve survival outcomes for patients with non-HGSC undergoing NAC.

PMID- 30187697
TI  - Stereotactic Body Radiotherapy: Does It Have a Role in Management of
      Hepatocellular Carcinoma?
AB  - Stereotactic body radiotherapy (SBRT) is a form of radiotherapy that delivers
      high doses of irradiation with high precision in a small number of fractions.
      However, it has not frequently been performed for the liver due to the risk of
      radiation-induced liver toxicity. Furthermore, liver SBRT is cumbersome because
      it requires accurate patient repositioning, target localization, control of
      breathing-related motion, and confers a toxicity risk to the small bowel.
      Recently, with the advancement of modern technologies including intensity
      modulated RT and image-guided RT, SBRT has been shown to significantly improve
      local control and survival outcomes for hepatocellular carcinoma (HCC),
      specifically those unfit for other local therapies. While it can be used as a
      stand-alone treatment for those patients, it can also be applied either as an
      alternative or as an adjunct to other HCC therapies (e.g., transarterial
      chemoembolization, and radiofrequency ablation). SBRT might be an effective and
      safe bridging therapy for patients awaiting liver transplantation. Furthermore,
      in recent studies, SBRT has been shown to have a potential role as an
      immunostimulator, supporting the novel combination strategy of immunoradiotherapy
      for HCC. In this review, the role of SBRT with some technical issues is
      discussed. In addition, future implications of SBRT as an immunostimulator are
      considered.

PMID- 30187700
TI  - Clinical Implications of Moderate Coronary Stenosis on Coronary Computed
      Tomography Angiography in Patients with Stable Angina.
AB  - PURPOSE: The present study investigated the diagnostic accuracy and clinical
      implications of moderate stenosis (50-69%, Coronary Artery Disease Reporting and
      Data System, grade 3) on coronary computed tomography angiography (CCTA),
      compared with invasive coronary angiography (ICA). MATERIALS AND METHODS: Two
      hundred and seventy-six patients who underwent ICA due to moderate stenosis alone
      on CCTA were selected from our prospective registry cohort. RESULTS: Diagnostic
      concordance between CCTA and ICA was found in only 50 (18%) patients. Among the
      396 vessels and 508 segments with moderate stenosis, diagnostic concordance was
      found in 132 vessels (33%) and 127 segments (25%). Segments with calcified plaque
      had lower diagnostic concordance than those with mixed or non-calcified plaque
      (22% vs. 28% vs. 27%, respectively, p=0.001). While calcified plaque burden did
      not have an influence on severe stenosis (>=70%) on ICA, higher burden of non
      calcified plaque was correlated with a greater incidence of ICA-based severe
      stenosis, which was more frequent in patients with >=3 segments of non-calcified
      plaque (75%) than those without non-calcified plaque (22%, p<0.001). Typical
      angina and mixed or non-calcified plaque were correlated with a higher incidence
      of under-diagnosis, while the use of next-generation computed tomography scanners
      reduced the incidence of under-diagnosis. Increased body weight, left circumflex
      artery involvement, and calcified plaque were independent factors that increased
      the risk of over-diagnosis of CCTA. CONCLUSION: The diagnosis of moderate
      stenosis by CCTA may be limited in estimating the exact degree of ICA-based
      anatomical stenosis. Unlike calcific burden, non-calcific burden was positively
      correlated with the presence of severe stenosis on ICA.

PMID- 30187701
TI  - Regulation of Colonic Mucosal MicroRNA Expression via Multiple Targets in
      Visceral Hypersensitivity Rats by Tongxieyaofang.
AB  - PURPOSE: This study aimed to screen for differentially expressed microRNAs
      (miRNAs) in the colons of rats with visceral hypersensitivity to build the
      expression profiles of miRNAs therein and to determine the mechanism of
      Tongxieyaofang use in the treatment of irritable bowel syndrome (IBS). MATERIALS
      AND METHODS: Forty Sprague-Dawley rats were divided randomly into four groups:
      control group, model control group (induced by rectum stimulus and evaluated by
      abdominal withdraw reaction), treatment control group (normal saline), and
      Tongxieyaofang group (treated with Tongxieyaofang). We screened for differential
      expression of colonic mucosal miRNAs using liquid chip technology and verified
      the expression thereof using reverse transcription-PCR. RESULTS: The visceral
      hypersensitivity rat model was successfully established. We found the expression
      of let-7f, let-7i, miR-130b, miR-29a, miR-132, miR-21, and miR-375 to be up
      regulated (p<0.05), while the expression of miR-24, miR-31a, miR-192, miR-221,
      and miR-223 was down-regulated (p<0.05) in the visceral hypersensitivity rats.
      After treatment with Tongxieyaofang, the expression of let-7f, let-7i, miR-130b,
      miR-29a, miR-132, miR-21, and miR-375 was reduced (p<0.05), whereas the
      expression of miR-24, miR-31a, miR-192, miR-221, miR-223 was increased, compared
      to the treatment control group (p<0.05). CONCLUSION: MiRNAs play a pivotal role
      in visceral hypersensitivity and might be targets in the treatment of IBS by
      Tongxieyaofang.

PMID- 30187702
TI  - Prospective Single Arm Study on the Effect of Ilaprazole in Patients with
      Heartburn but No Reflux Esophagitis.
AB  - PURPOSE: Patients with gastroesophageal reflux disease without esophagitis show
      varying responses to proton pump inhibitors (PPIs). The aim of this study was to
      objectively evaluate the effect of a new PPI, ilaprazole, on patients with
      heartburn but without reflux esophagitis. MATERIALS AND METHODS: This prospective
      study was performed on 20 patients with heartburn but without reflux esophagitis.
      All patients underwent upper endoscopy and 24-hr combined multichannel
      intraluminal impedance and pH esophageal monitoring (MII-pH). They were then
      treated with ilaprazole (20 mg) once daily for 4 weeks. The GerdQ questionnaire,
      histologic findings, and inflammatory biomarkers were used for assessment before
      and after ilaprazole. RESULTS: Among the 20 patients, 13 (65%) showed GerdQ score
      >=8. Based on MII-pH results, patients were classified as true nonerosive reflux
      disease (n=2), hypersensitive esophagus (n=10), and functional heartburn (n=8).
      After treatment, patients showed a statistically significant improvement in GerdQ
      score (p<0.001). Among histopathologic findings, basal cell hyperplasia,
      papillary elongation, and infiltration of intraepithelial T lymphocytes improved
      significantly (p=0.008, p=0.021, and p=0.008; respectively). Expression of TNF
      alpha, IL-8, TRPV1, and MCP-1 decreased marginally after treatment (p=0.049,
      p=0.046, p=0.045, and p=0.042; respectively). CONCLUSION: Daily ilaprazole (20
      mg) is efficacious in improving symptom scores, histopathologic findings, and
      inflammatory biomarkers in patients with heartburn but no reflux esophagitis.

PMID- 30187703
TI  - Beneficial Role of Hydrogen Sulfide in Renal Ischemia Reperfusion Injury in Rats.
AB  - PURPOSE: Hydrogen sulfide (H2S) is an endogenous gaseous molecule with important
      physiological roles. It is synthesized from cysteine by cystathionine gamma-lyase
      (CGL) and cystathionine beta-synthase (CBS). The present study examined the
      benefits of exogenous H2S on renal ischemia reperfusion (IR) injury, as well as
      the effects of CGL or CBS inhibition. Furthermore, we elucidated the mechanism
      underlying the action of H2S in the kidneys. MATERIALS AND METHODS: Thirty male
      Sprague-Dawley rats were randomly assigned to five groups: a sham, renal IR
      control, sodium hydrosulfide (NaHS) treatment, H2S donor, and CGL or CBS
      inhibitor administration group. Levels of blood urea nitrogen (BUN), serum
      creatinine (Cr), renal tissue malondialdehyde (MDA), and superoxide dismutase
      (SOD) were estimated. Histological changes, apoptosis, and expression of mitogen
      activated protein kinase (MAPK) family members (extracellular signal-regulated
      kinase, c-Jun N-terminal kinase, and p38) were also evaluated. RESULTS: NaHS
      attenuated serum BUN and Cr levels, as well as histological damage caused by
      renal IR injury. Administration of NaHS also reduced oxidative stress as evident
      from decreased MDA, preserved SOD, and reduced apoptotic cells. Additionally,
      NaHS prevented renal IR-induced MAPK phosphorylation. The CGL or CBS group showed
      increased MAPK family activity; however, there was no significant difference in
      the IR control group. CONCLUSION: Exogenous H2S can mitigate IR injury-led renal
      damage. The proposed beneficial effect of H2S is, in part, because of the anti
      oxidative stress associated with modulation of the MAPK signaling pathways.

PMID- 30187705
TI  - Efficacy and Safety of Robotic Procedures Performed Using the da Vinci Robotic
      Surgical System at a Single Institute in Korea: Experience with 10000 Cases.
AB  - PURPOSE: To evaluate the efficacy and safety of robotic procedures performed
      using the da Vinci Robotic Surgical System at a single institute. MATERIALS AND
      METHODS: We analyzed all robotic procedures performed at Severance Hospital,
      Yonsei University Health System (Seoul, Korea). Reliability and mortality rates
      of the robotic surgeries were also investigated. RESULTS: From July 2005 to
      December 2013, 10267 da Vinci robotic procedures were performed in seven
      different departments by 47 surgeons at our institute. There were 5641 cases
      (54.9%) of general surgery, including endocrine (38.0%), upper (7.7%) and lower
      gastrointestinal tract (7.5%), hepato-biliary and pancreatic (1.2%), and
      pediatric (0.6%) surgeries. Urologic surgery (33.0%) was the second most common,
      followed by otorhinolaryngologic (7.0%), obstetric and gynecologic (3.2%),
      thoracic (1.5%), cardiac (0.3%), and neurosurgery (0.1%). Thyroid (40.8%) and
      prostate (27.4%) procedures accounted for more than half of all surgeries,
      followed by stomach (7.6%), colorectal (7.5%), kidney and ureter (5.1%), head and
      neck (4.0%), uterus (3.2%), thoracic (1.5%), and other (2.9%) surgeries. Most
      surgeries (94.5%) were performed for malignancies. General and urologic surgeries
      rapidly increased after 2005, whereas others increased slowly. Thyroid and
      prostate surgeries increased rapidly after 2007. Surgeries for benign conditions
      accounted for a small portion of all procedures, although the numbers thereof
      have been steadily increasing. System malfunctions and failures were reported in
      185 (1.8%) cases. Mortality related to robotic surgery was observed for 12
      (0.12%) cases. CONCLUSION: Robotic surgeries have increased steadily at our
      institution. The da Vinci Robotic Surgical System is effective and safe for use
      during surgery.

PMID- 30187704
TI  - Proper Cut-off Levels of Serum Specific IgE to Cefaclor for Patients with
      Cefaclor Allergy.
AB  - PURPOSE: Cefaclor, a second-generation oral cephalosporin, is known to cause IgE
      mediated hypersensitivity. Assays of serum-specific IgE (sIgE) to cefaclor are
      commercially available via the ImmunoCAP system (Thermo Fisher Scientific). While
      serum levels of sIgE >0.35 kU/L are considered indicative of an allergy, some
      patients with cefaclor allergy show low serum IgE levels. This study aimed to
      evaluate the proper cut-off levels of sIgE in the diagnosis of immediate
      hypersensitivity to cefaclor. MATERIALS AND METHODS: A total of 269 patients with
      drug allergy history, who underwent assays of sIgE to cefaclor at Ajou University
      hospital and Dong-A University Hospital, were reviewed retrospectively. Among
      them, 193 patients exhibited cefaclor-induced immediate hypersensitivity with
      certain or probable causality of an adverse drug reaction according to the WHO
      UMC (the World Health Organization-the Uppsala Monitoring Centre) algorithm, and
      76 controls showed delayed hypersensitivity reactions to non-antibiotics.
      RESULTS: In total, 126 of the 193 patients (65.3%) experienced anaphylaxis; they
      had higher serum sIgE levels than patients with immediate hypersensitivity who
      did not experience anaphylaxis (6.36+/-12.39 kU/L vs. 4.28+/-13.61 kU/L,
      p<0.001). The best cut-off value for cefaclor-induced immediate hypersensitivity
      was 0.11 kU/L, with sensitivity of 80.2% and specificity of 81.6%. A cut-off
      value of 0.44 kU/L showed the best sensitivity (75.4%) and specificity (65.7%)
      for differentiating anaphylaxis from immediate hypersensitivity reactions.
      CONCLUSION: Patients with cefaclor anaphylaxis exhibit high serum IgE levels. A
      cut-off value of 0.11 kU/L of sIgE to cefaclor is proper for identifying patients
      with cefaclor allergy, and 0.44 kU/L may be useful to detect anaphylaxis.

PMID- 30187706
TI  - Relative Risk and Clinical Severity Assessment in Patients with Non-Oral Route
      Organophosphate Poisoning Compared with Oral Route Poisoning.
AB  - PURPOSE: Organophosphates, commonly used in agricultural pesticides, pose high
      risks and incidences of poisoning. In the present study, we investigated the
      relative risk and clinical severity, including laboratory results, of non-oral
      route poisoning (NORP) patients, compared to oral route poisoning (ORP) patients.
      MATERIALS AND METHODS: A single institutional toxicology database registry was
      utilized to gain information on clinical laboratory results on organophosphate
      poisoning patients who visited the emergency department (ED) between January 2000
      and October 2016. Clinical outcomes, such as mortality and complication rates,
      were compared using 1:2 propensity score matching in the total cohort. RESULTS:
      Among a total of 273 patients in our study, 34 experienced NORP. After 1:2
      propensity score matching, rates of respiratory complications and mortality were
      higher in the ORP group than in the NORP group. However, there was no difference
      in hospitalization time and time spent in the intensive care unit between the two
      groups. Compared with ORP patients after matching, the relative risk of mortality
      in NORP patients was 0.34, and the risk of respiratory distress was 0.47. The
      mean level of pseudocholinesterase was significantly higher in the NORP group
      than in the ORP group, while recovery rates were similar between the two groups.
      CONCLUSION: Although the majority of NORP patients were admitted to the ED with
      unintentional poisoning and the relative risk of NORP was lower than that for
      ORP, we concluded that NORP is as critical as ORP. Considerable medical
      observation and intensive therapeutic approaches are also needed for NORP
      patients.

PMID- 30187707
TI  - Pediatric Trampoline-Related Injuries in a Nationwide Registry in South Korea,
      2011 to 2016.
AB  - PURPOSE: Trampoline-related injuries are steadily increasing. To our knowledge,
      there have been very few studies on trampoline injuries in Asia. The purpose of
      this study is to report the characteristics of pediatric trampoline injuries in
      Korea. MATERIALS AND METHODS: We conducted a nationwide retrospective cohort
      study. Data were collected from prospective nationwide databases (Emergency
      Department-based Injury In-depth Surveillance databases of the Korea Centers for
      Disease Control and Prevention) for patients who visited emergency departments
      (EDs) after injuries during 2011-2016. RESULTS: Of 263712 patients between 0 and
      17 years of age, 2799 patients with trampoline injuries visited EDs. The median
      age of the patients was 5 years (interquartile range, 3-8 years), and 63% of the
      patients were under 6 years old. Of the patients, 1526 (54.2%) were male. Seventy
      six percent of injuries occurred at trampoline parks. Trampoline injuries and
      trampoline park injuries have increased steadily, while ages at injury have
      gradually decreased year by year (p<0.001). Injury locations included the lower
      extremity (47%), head and face (24%), and upper extremity (24%). A fracture was
      sustained by 886 (31.7%) patients. The distal humerus and proximal tibia were the
      most common fracture sites (34% and 23%, respectively). Fractures occurred more
      commonly in trampoline parks than in homes (33.7% vs. 21.1%, p<0.001).
      CONCLUSION: In Korea, pediatric trampoline injuries and trampoline park injuries
      have tended to increase, while ages at injury have tended to decrease. Policies
      to prevent trampoline injuries are needed.

PMID- 30187708
TI  - Development of a Novel Nonradioisotopic Assay and Cdc25B Overexpression Cell
      Lines for Use in Screening for Cdc25B Inhibitors.
AB  - PURPOSE: The cyclin-dependent kinase 1 (Cdk1) and cyclin B complex performs
      important roles in the transition from the G2 to M phase in the cell cycle
      through removal of inhibitory phosphates on Cdk1, and Cdc25B, which is a dual
      specific phosphatase, mediates these dephosphorylation events. However, measuring
      Cdc25B activity by existing methods is hampered by inadequate nonspecific
      substrates and the need to use a radiolabeled isotope. The present study aimed to
      develop an improved method with which to properly measure Cdc25B activity using a
      novel nonradioisotopic assay and Cdc25B overexpression cell lines. MATERIALS AND
      METHODS: A nonradioisotopic Cdk1 kinase assay, based on Western blotting for
      retinoblastoma protein and histone H1, was used to analyze Cdc25B activity. Also,
      stable Cdc25B2 and Cdc25B3 overexpression HeLa cell lines were constructed using
      the tetracycline-regulated expression system and were applied as a tool for
      screening for inhibitors of Cdc25B. RESULTS: The present study developed and
      optimized a nonradioisotopic assay method to properly measure Cdc25B activity.
      Furthermore, we constructed stable Cdc25B2 and Cdc25B3 overexpression HeLa cell
      lines for the establishment of a strong assay system with which to evaluate the
      specificity of Cdc25B inhibitors under conditions similar to the intracellular
      environment. These methods were confirmed as useful tools for measuring Cdc25B
      activity. CONCLUSION: The nonradioisotopic Cdk1 kinase assay and Cdc25B
      overexpression cell lines developed in this study can be conveniently used as
      tools for screening inhibitors of Cdc25B phosphatase as anticancer drugs.

PMID- 30187710
TI  - Genotypic and Phenotypic Heterogeneity of LGMD1D due to DNAJB6 Mutations.

PMID- 30187709
TI  - Bronchiectasis and Recurrent Respiratory Infections with a De Novo STAT1 Gain-of
      Function Variant: First Case in Korea.
AB  - Bronchiectasis is a chronic disease characterized by airway infection and
      inflammation, leading to permanent dilation of the bronchi. Evaluation of
      underlying etiology is important in managing young bronchiectasis patients with
      recurrent infections caused by unusual pathogens. The signal transducer and
      activator of transcription 1 (STAT1) protein plays a key role in STAT signaling
      and immune system regulation. Heterozygotes for gain-of-function (GOF) alleles of
      the STAT1 gene usually display autosomal dominant chronic mucocutaneous
      candidiasis (CMC) and a wide range of clinical features, such as bronchiectasis.
      Here, we report on a patient with CMC and bronchiectasis with various types of
      infections who carried a pathogenic variant of the STAT1 gene. The 24-year-old
      female presented with recurrent respiratory bacterial and nontuberculous
      mycobacterial infections complicated by severe bronchiectasis and CMC. Whole
      exome sequencing revealed a c.800C>T (p.Ala267Val) heterozygous mutation in the
      STAT1 gene. Further analysis by Sanger sequencing of STAT1 from the patient and
      her parents revealed the patient had a de novo occurrence of the variant. This is
      the first report of a Korean patient with a GOF pathogenic variant in STAT1.
      Physicians should be aware of the existence of this variant as a genetic factor
      associated with CMC and bronchiectasis complicated by recurrent infection.

PMID- 30187711
TI  - The Author Reply: Genotypic and Phenotypic Heterogeneity of LGMD1D due to DNAJB6
      Mutations.

PMID- 30187712
TI  - In vitro culture of mammalian inner ear hair cells.
AB  - Auditory function in vertebrates depends on the transduction of sound vibrations
      into electrical signals by inner ear hair cells. In general, hearing loss
      resulting from hair cell damage is irreversible because the human ear has been
      considered to be incapable of regenerating or repairing these sensory elements
      following severe injury. Therefore, regeneration and protection of inner ear hair
      cells have become an exciting, rapidly evolving field of research during the last
      decade. However, mammalian auditory hair cells are few in number, experimentally
      inaccessible, and barely proliferate postnatally in vitro. Various in vitro
      primary culture systems of inner ear hair cells have been established by
      different groups, although many challenges remain unresolved. Here, we briefly
      explain the structure of the inner ear, summarize the published methods of in
      vitro hair cell cultures, and propose a feasible protocol for culturing these
      cells, which gave satisfactory results in our study. A better understanding of in
      vitro hair cell cultures will substantially facilitate research involving
      auditory functions, drug development, and the isolation of critical molecules
      involved in hair cell biology.

PMID- 30187713
TI  - Use of Plant Extracts in Alternative Medicine.
AB  - Plants provide the oxygen required for maintenance of human life. They are
      essential for human life in terms of food and health. Thousands of years ago,
      humans explored the therapeutic power of plants and preferred to benefit from
      them to live healthily. According to the data of the World Health Organization
      (WHO), the number of plants used for therapeutic purposes is around 20,000. Since
      the beginning of using plants for human health, the bioactivity characteristics
      of the plants have been studied in laboratories. There are various bioactive
      components in plants, the most important of which are secondary metabolites. It
      is very important how and by which methods the secondary metabolites of plants
      are characterized as well as their isolation, proper and effective performance of
      their extraction process and identification of their various biological
      activities that might be used in alternative medicine. This review examines the
      usability of supplementary medical support products after the identification of
      bioactive characteristics of plants by means of various biochemical and molecular
      biological methods.

PMID- 30187714
TI  - Allelopathic Effects of Three Sweet Potato Cultivars (Ipomoea batatas) on the
      Invasive Plant Mikania micrantha.
AB  - BACKGROUND AND OBJECTIVES: Sweet potato [Ipomoea batatas (L.) Lam] is an
      important locally grown cash crop in China; it was demonstrated to suppress the
      invasive plant Mikania micrantha (M. micrantha) H.B.K through strong
      competitiveness, but its allelopathic effects on this weed were unknown. The
      present study aimed to explore the allelopathic potential of sweet potato on M.
      micrantha. MATERIALS AND METHODS: The allelopathic effects of water extracts and
      soil incorporation from leaves of three sweet potato cultivars (SP1, SP0 and SP9)
      on the sprout seedling growth of invasive plant M. micrantha in Yunnan Province,
      China, were studied under laboratory and greenhouse conditions. RESULTS: Stem
      length, root biomass, aboveground biomass and total biomass of M. micrantha were
      significantly reduced with increasing concentration in both leaf water extracts
      and leaf soil incorporation of three sweet potato cultivars. Among these, SP1 had
      the strongest inhibition and the next highest impact was from SP0 with the lowest
      effect from SP9. The highest inhibition rates were seen for root biomass,
      followed by total biomass, whereas the lowest impact was on aboveground biomass.
      The strong correspondence between results for both leaf water extracts and leaf
      soil incorporation provided a good demonstration that compounds produced by sweet
      potato have allelopathic effects on M. micrantha. The general inhibition of M.
      micrantha by sweet potato followed the order among the three sweet potato
      cultivars tested as SP1, SP0 and SP9. Moreover, the synthetical allelopathic
      indices of leaf soil incorporation of three cultivars on M. micrantha were
      generally higher than these of leaf water extracts. CONCLUSION: Competition and
      allelopathy have primarily been seen as separate ecological weed management
      tools, but as these have demonstrated in the case of sweet potato where both
      mechanisms inhibit weed growth, there is potential for synergism between
      competition and allelopathy in the reduction of weed infestations.

PMID- 30187715
TI  - Identification and Pathogenicity of Fungal Dieback Disease on Sengon
      (Paraserianthes falcataria (L.) Nielsen) Seedling and Rice (Oryza sativa).
AB  - BACKGROUND AND OBJECTIVE: Sengon (Paraserienthes falcataria (L.) Nielsen) is a
      plant species in forestry plantation while rice (Oryza sativa) is an agricultural
      crop which potentially used in the agroforestry system. Both species are
      susceptible to dieback disease. This study aimed to isolate and identify the
      dieback disease on sengon seedlings to understand the pathogenicity of fungal
      dieback disease on the seedlings of both sengon and rice and to observe the
      symptom of dieback disease both macroscopically and microscopically. MATERIALS
      AND METHODS: Pathogenicity test was conducted in a factorial completely
      randomized design (CRD). The treatments were control, wounded by carborundum,
      inoculated with pathogen as well as inoculated with pathogen and wounded by
      carborundum. RESULTS: Results revealed that the greatest percentage of dieback
      disease on sengon and rice was occurred on the treatment of inoculation with
      wound both100%. While, the greatest percentage of dieback disease intensity of
      sengon and rice was obtained on the treatment of inoculation with wound by 98.2
      and 40.6%, respectively. The PCR result identified that the pathogen was
      Ceratobasidium ramicola that form imperfect state as Rhizoctonia sp. CONCLUSION:
      This species of fungal pathogen is the major cause of dieback disease on sengon
      and rice seedlings due to seedlings death.

PMID- 30187716
TI  - Aerobic Profile During High-intensity Performance in Professional Saudi Athletes.
AB  - BACKGROUND AND OBJECTIVE: The aerobic power, expressed relative to body mass, of
      different Saudi elite players is one of the most important area of interest and
      with great values because of its restrictively that reported in the previously
      literatures, the present study was conducted to investigate the aerobic
      characteristics of Saudi elite, Saudi triathlon and soccer players and to compare
      between measures of aerobic power between both players using graded treadmill
      protocol to assess maximal cardiorespiratory fitness (VO2max), within a groups of
      high trained youth Saudi elite players. MATERIALS AND METHODS: Twenty two
      professional Saudi athletes, 11 Saudi triathlon athletes, 11 Saudi soccer players
      were selected. Their Mean+/-SD for age, height, weight, body mass index (BMI),
      body fat mass (%), body fat free mass percentage, cardiovascular parameter,
      including, absolute and relative peak oxygen consumption "VO2max" and maximal
      heart rate "HR max". Data were analyzed using independent sample t-test and SPSS
      software. RESULTS: Descriptive statistics for anthropometric characteristics were
      performed to compare between the means, independent sample. T-test showed mean
      value of absolute "VO2max" (3605.18+/-515.74), for triathlon athletes, while
      football players absolute VO2max, (3645.63+/-897.60) with non-significant
      different between the groups. Overall mean of peak training values was (3625.40
      mL min-1), relative VO2max was appears to be (53.46+/-7.242) mL-1 min-1 kg-1, for
      triathlon athletes, while football athletes relative VO2max has a mean value and
      +/-SD of (52.35+/-6.342) mL-1 min-1 kg-1 with non-significant different between
      the groups. HR max was (157.90+/-8.167) beats min-1 for triathlon athletes, while
      football players HR max, was (139.18+/-6.646) beats min-1 with non-significant
      difference between the groups. CONCLUSION: This clinical approaches that use
      Cardio Pulmonary Exercise Testing (CPET) in performance testing revealed that
      aerobic power, expressed relative to body mass, of Saudi soccer players was in
      the near range of values normally reported in the literatures for soccer players
      and triathletes during exercise training as well. Degrees of aerobic achievements
      during both exercise testing seems to be with non-significant different between
      Saudi soccer player and Saudi triathlon.

PMID- 30187717
TI  - Effects of Adding Chicken Blood Meal and Fishmeal to Sludge Biogas as White
      Oyster Mushroom Media.
AB  - BACKGROUND AND OBJECTIVE: The biogas sludge is generally not used optimally and
      people even pour it directly into the river that it cause environmental
      pollution. One of the ways to get the benefit from sludge and chicken blood meal
      or fishmeal is to use it as a substitute for bran in mushroom media. This study
      aimed to improve the nutrient content of biogas sludge with the addition of
      chicken blood meal (CBM) and fishmeal (FM) as substitute material for bran in
      white oyster mushroom media. MATERIALS AND METHODS: The biogas sludge was dried
      in the sun for 3 days until its form resembled the soil. The treatment consisted
      of dried biogas sludge without CBM (BP0), dried biogas sludge with 1% CBM (BP1)
      and dried biogas sludge with 3% CBM (BP2). Each was added to the media of white
      oyster mushroom as much as 15% as substitute material for bran. The other
      treatment consisted of dried biogas sludge without FM (FP0), dried biogas sludge
      with 2% FM (FP1) and dried biogas sludge with 4% FM (FP2). Each was added to the
      media of white oyster mushroom as much as 5% as substitute material for bran. BP0
      and FP0 created from white oyster mushroom media were commonly used by farmers.
      Each treatment was analyzed of nutritional and biological contents. All the data
      were tested using completely randomized design one-way ANOVA. RESULTS: The
      results of the research on the use of chicken blood meal and fishmeal showed that
      the best treatments were BP2 and FP2. Their nutrient content increased, including
      the organic-C, organic matter, nitrogen, P2O5 and K2O. The productivity of the
      oyster mushroom increased, shown by the increase of fresh weight and diameter of
      caps in treatment BP2. The replacement of bran by biogas sludge with 4% FM
      addition (FP2) in oyster mushroom media increased the fresh weight, the number of
      caps and the length of oyster mushroom stalks. CONCLUSION: The best treatments
      for mushroom media were BP2 and FP2 to be used as substitute material for bran in
      white oyster mushroom media.

PMID- 30187718
TI  - Molecular Characterization of Dengue E/NS1 Junction Genotype 2 Isolated From
      Saudi Patients, Jeddah Province.
AB  - BACKGROUND AND OBJECTIVE: Dengue is the most important arthropod-borne viral
      disease which caused by the four-dengue virus serotypes (1-4) and its incidence
      has grown dramatically around the world in the recent decades. This study was
      conducted to determine the molecular characterization of dengue virus genotypes
      spreading in Jeddah province. METHODOLOGY: To distinguish dengue virus genotypes,
      serum samples from 13 infected patients were subjected to envelop and non
      structural 1 (E/NS1) gene amplification and sequence analysis at the nucleotide
      and amino acid levels. RESULTS: The present partial dengue virus phylogenetic
      analysis announced the domination of dengue virus 2 genotype among the current
      dengue virus samples circulating in Jeddah province. Dengue virus 2 current
      isolates were grouped in one branch and seemed to be more closely related to
      various strains isolated from Sri-Lanka, Australia and Singapore and confirmed by
      internucleotide distance average ranged +/-0.01. Interestingly, sequences
      analysis of amino acids confirmed substitution of 8 amino acid residue
      (Ser729Gua, Ser729Arg, Val762Gau, Val780phe, Val781Leu, Val781Ala, Glu858Asp and
      Gln873His) among the present isolates comparing with previous references strains
      isolated from different countries. Remarkably, one unique amino acid residue
      Ala741Val was verified in the 10 present isolates compared to the reference
      sequence previously isolated from Jeddah. CONCLUSION: Notably, the present study
      demonstrated the sequencing analysis of the dengue virus 2-E/NS1 on both
      nucleotide and amino acid levels and confirmed its endogenously prevalence in
      Jeddah.

PMID- 30187719
TI  - Investigation on Inhibitory Potential of <I>Myrmecodia tuberosa </I>on Quorum
      Sensing-related Pathogenicity in <I>Pseudomonas aeruginosa</I> PAO1 and
      <I>Staphylococcus aureus </I>Cowan I Strains.
AB  - BACKGROUND AND OBJECTIVES: Tuber of Myrmecodia tuberosa Jack (Rubiaceae) has been
      widely used as herbal remedy in Indonesia. This research aimed to evaluate the
      effects of M. tuberosa Jack on quorum-sensing related pathogenicity of
      Pseudomonas aeruginosa and Staphylococcus aureus. MATERIALS AND METHODS:
      Following delipidation with petroleum ether, pulverized tuber was macerated in
      methanol. After evaporation to obtain methanol extract, liquid-liquid partition
      was perform on the extract to yield hexane, ethyl acetate and water fractions.
      The extract and fractions were screened for the effects on the planktonic growth
      of P. aeruginosa and S. aureus. Inhibition of pigment production was observed on
      cetrimide Agar following sample treatment on Pseudomonas aeruginosa. Samples were
      prepared as 2-0.0625 mg mL-1 concentration. The effects on swimming, swarming and
      twitching motility of Pseudomonas aeruginosa PAO1 following sample application
      were observed. All experiments were done in triplicate. RESULTS: Results showed
      that the ethyl acetate fraction caused a prominent effect on quorum sensing
      inhibition which might explain its biofilm inhibition effect on P. aeruginosa.
      Significant inhibitory effect in a concentration dependent manner towards pigment
      production inhibitor and motilities were observed over control. CONCLUSION:
      Despite being active as planktonic growth inhibitor towards S. aureus and P.
      aeruginosa, M. tuberosa ethyl acetate fraction is recommended to be investigated
      further as anti-infective against P. aeruginosa.

PMID- 30187722
TI  - Health Implications Associated with Aspartame Consumption: A Substantial Review.
AB  - Aspartame, an artificial sweetening agent belongs to dipeptide chemical category
      with a very strong sweetening potential. Although research findings in humans and
      non-human primates have demonstrated numerous negative effects of aspartame
      (biochemical, histological, neurological, behavioral, genetic etc)., the status
      of aspartame is still debatable. Present manuscript is a critical review of the
      substantial research findings related to aspartame intake on different research
      models. Purpose of this review was to spread the awareness about adverse effect
      of aspartame intake to outline the occurrence of health issues among the
      population. The process of uptake, storage, compartmentalization and distribution
      of aspartame within the body is associated with metabolic disorders and various
      clinical conditions. Available research literature indicates that higher amount
      of aspartame ingestion should be monitored carefully to avoid health implication
      within society.

PMID- 30187720
TI  - Effect of Partial Substitution of Ration's Soybean Meal by Biologically Treated
      Feathers on Rumen Fermentation Characteristics (<I>in vitro</I>).
AB  - BACKGROUND AND OBJECTIVE: Feather wastes are the most abundant keratinous
      material in the nature and its accumulation causes multiple environmental
      problems. Nutritive value upgrading of such wastes through biological treatments
      may provide ruminant's rations with high quality and cost effective source of
      protein. Therefore, the main objective of this study was to investigate the
      potential uses of biologically treated feathers (BTF) as a feedstuff for
      ruminants through in vitro experiments. MATERIALS AND METHODS: Keratinase
      production time course was performed by ten microbial isolates (3 fungal, 3
      actinomyces and 4 bacterial isolates) under static and shaking conditions using
      turkey feather- synthetic medium. The chemical composition and amino acid
      analysis for the crude feathers, BTF and soybean meal were determined according
      to AOAC methods. Two in vitro experiments were conducted to study the effects of
      crude feathers, BTF and modified ruminant rations (in which soybean meal were
      substituted by the BTF in 10, 20 and 30%) on rumen fermentation characteristics.
      Ration's Dry Matter (DM), Organic Matter (OM), Neutral detergent fibre (NDF) and
      Acid detergent Fibre (ADF) degradability by rumen microorganisms were tested
      using batch culture technique. Ruminal final pH, ammonia-nitrogen, total volatile
      fatty acids and short chain fatty acids concentrations were determined after 24 h
      of incubation. The total gas production volume was determined using 100 mL glass
      syringes. RESULTS: Bacillus licheniformis ALW1 was the most potent keratinase
      producer strain under static condition at 37 degrees C for four days of
      incubation. Feather biological treatment by Bacillus licheniformis increased its
      content of some of essential-sulphur amino acids. The degradability of BTF by
      rumen microorganisms was 4 folds higher than crude feather degradability. There
      were no significant differences between control and partially substituted (R10
      and R20) rations in all of rumen fermentation characteristics. CONCLUSION: The
      utilization of BTF as substitute for costly soybean meal in ruminant's rations up
      to 20% had no negative effect on all rumen fermentation characteristics.

PMID- 30187721
TI  - Cq1 Exon Polymorphisms in Caucasian and African American Systemic Lupus
      Erythematosus patients.
AB  - BACKGROUND: C1q protein is composed of three protein chains (A, B and C) that are
      the products of separate genes. Genetic deficiencies in C1Q genes are important
      factors influencing the risk of systemic lupus erythematosus (SLE). Therefore,
      this study aimed to investigate the possible association of single nucleotide
      polymorphisms (SNPs) in the coding region of the C1Q genes with SLE. METHODS: To
      search for potential SNPs in the encoding regions of C1q A, B and C chains, Cq1
      exons were initially amplified and directly sequenced from leukocyte DNA from a
      subset of Caucasian and African American SLE patients and healthy controls. The
      sequences were analyzed by the Phrap and Phred software analysis system and the
      SNPs were identified by visual inspection. To test if any of these SNPs were
      linked to susceptibility to SLE, they were measured in 210 SLE patients ((59
      African Americans and 151 Caucasians) and 129 matched healthy controls (55
      African Americans and 74 Caucasians) by restriction fragment length polymorphism
      analysis. RESULTS: The sequencing phase of the study identified three synonymous
      SNPs: Nucleotide 276G>A in C1QA, 66C>A in C1QB and 129G>A in C1QC. Statistically,
      no differences were found in genotype or allele frequencies between patients and
      controls for the 276G>A or 66C>A SNP. However, in Caucasians, the frequencies of
      the 129G>A genotypes were significantly different between SLE patients and
      controls (P = 0.005), specifically with the GG genotype being over represented in
      the controls (P = 0.004). CONCLUSION: The results show that the homozygous 129GG
      genotype is associated with protection against SLE onset. This protection is race
      dependent, being observed in Caucasians but not African Americans. The mechanism
      of this association is currently unclear.

PMID- 30187723
TI  - Immunotherapy a New Hope for Cancer Treatment: A Review.
AB  - Cancer is a major burden of disease worldwide with considerable impact on
      society. The tide of immunotherapy has finally changed after decades of
      disappointing results and has become a clinically validated treatment for many
      cancers. Immunotherapy takes many forms in cancer treatment, including the
      adoptive transfer of ex vivo activated T cells, oncolytic viruses, natural killer
      cells, cancer vaccines and administration of antibodies or recombinant proteins
      that either costimulate cells or block the so-called immune checkpoint pathways.
      Recently, cancer immunotherapy has received a high degree of attention, which
      mainly contains the treatments for programmed death ligand 1 (PD-L1), programmed
      death 1 (PD-1), chimeric antigen receptors (CARs) and cytotoxic T lymphocyte
      associated antigen 4 (CTLA-4). Here, this paper reviewed the current
      understandings of the main strategies in cancer immunotherapy (adoptive cellular
      immunotherapy, immune checkpoint blockade, oncolytic viruses and cancer vaccines)
      and discuss the progress in the synergistic design of immune-targeting
      combination therapies.

PMID- 30187724
TI  - Molecular Modulation of Stress Induced to Abnormal Haematological Indices in
      Medical Students, Malaysian Perspective.
AB  - Medical students in Malaysia and globally were considered among the most exposure
      groups in the community to stress due to several sources. The most significant
      and severe sources of stress in medical students is an academic sources, includes
      a lot of exams/tests, lack of time and facilities for entertainment, stay in a
      hostel, high parental expectations and vastness of syllabus, in addition to
      emotional problems and others personal sources. Stress is a very important issue
      that leads to a worsening of health problems. Stress develops in the body and
      leads to oxidative stress which in turn leads to a disorder in the whole body.
      Oxidative stress may lead to abnormal haematological indices elevated white blood
      cells (WBCs) count. Oxidative stress can lead to massive destruction of red blood
      cells (RBCs). The brain and the gastrointestinal system (GI) are intimately
      connected as one system. The brain has a direct impact on the GI tract. A
      stressful brain can send signals to the gut, just as a troubled intestine can
      send signals to the brain. Therefore, stress can be the cause of block the
      breakdown and assimilation of food for energy and nutriment. This malabsorption
      can then lead to a reciprocal negative effect to the stress and can be another
      cause of anaemia through malabsorption minerals and vitamins that are to
      erythropoiesis. So, stress can be one of the leading causes of anaemia among
      medical students. Stress is a chronic epidemic in the most medical students and
      can directly affect how well body works. This review article discovers the effect
      of stress in medical students that can be effect on their studies and further
      create researcher's interest to generate database that help to reduce stress
      response and bring about the empowerment of balanced life among Malaysian medical
      students besides the increasing level of health and academic performance.

PMID- 30187726
TI  - Evaluation of Antimicrobial Activities of Extract from <I>Pyrenacantha
      grandiflora</I> Baill. (Icacinaceae).
AB  - BACKGROUND AND OBJECTIVE: Microbial drug resistance is a growing health problem.
      This has led to search for new antimicrobial compound and plants are considered
      as one of the most promising sources for new antimicrobials discovery.
      Pyrenacantha grandiflora (P. grandiflora) Baill is used for the treatment and
      management of diarrhea, gastrointestinal related infections, dysentery,
      inflammation and tooth pain by traditional healers in the Venda region. The goal
      of the present study was to evaluate the antimicrobial activity of P. grandiflora
      tubers using different extraction solvents against 15 bacterial and 11 fungal
      strains. MATERIALS AND METHODS: Plant extracts were obtained using 5 solvents
      separately, boiled water, cold water, methanol, dichloromethane, chloroform and
      ethyl acetate. Hole plate assay was used for initial evaluation of antimicrobial
      properties of plant materials. Minimum inhibitory concentrations (MIC) of the
      most active plant extracts were determined by the broth microdilution method. One
      way ANOVA was used for data analysis. RESULTS: The hole plate assay revealed that
      the highest antibacterial activity was against Micrococcus kristinae with ethyl
      acetate extract and no extract was active against Candida and Fusarium species
      using this method. The MIC of the extracts was determined and all the extracts
      showed antimicrobial activity against all tested strains ranging from 0.06-7.5 mg
      mL-1. Some extract appeared to be fungicidal and hot water extract were more
      active against Cryptococcus neoformans with the MFC value of 0.06 mg mL-1.
      Methanol extract was also active against most test strains including Candida
      tropicalis with the minimum fungicidal concentration value of 3.75 mg mL-1.
      CONCLUSION: Pyrenacantha grandiflora contains substances that make it active
      against bacterial and fungal pathogens. This is the first time the antimicrobial
      and antifungal activities of P. grandiflora have been demonstrated
      scientifically. Extraction with hot water as done by the traditional healers
      showed activity thereby justifying the traditional use of this plant.

PMID- 30187725
TI  - Influence of Different Stocking Densities on Growth, Feed Efficiency and Carcass
      Composition of Bonylip Barb (<I>Osteochilus vittatus</I> Cyprinidae) Fingerlings.
AB  - BACKGROUND AND OBJECTIVE: Bonylip barb (Osteochilus vittatus) is an herbivorous
      freshwater fin-fish species native in Indonesia. These species has high demand
      and price in the market. A 90 days study was conducted to evaluate the effects of
      different stocking densities on growth, carcass composition, survival and water
      quality of Osteochilus vittatus (O. vittatus) in a synthetic sheet pond.
      MATERIALS AND METHODS: Fingerlings with an average weight of 2.45+/-0.071 g
      (Mean+/-SD) were randomly stocked in 12 synthetic sheet ponds (2*1 m) at
      densities of 50 fish m-3 (T50), 75 fish m-3 (T75), 100 fish m-3 (T100) and 125
      fish m-3 (T125) in triplicate groups. One-way ANOVA followed by Duncan's new
      multiple range test was used to analyze obtained data a significance level of
      p<0.05. RESULTS: After 90 days of the trial, the growth in terms of weight gain
      (WG) and specific growth rate (SGR) of fish from T50 were significantly higher
      than those from T75, T100 and T125. The feed conversion ratio (FCR) was
      significantly lower in T50 followed by T75, T100 and T125 consecutively. Protein
      efficiency ratio (PER) was higher in T50 followed by T75, T100 and T125
      consecutively. The survival rate (SR) of the fish from T50 was significantly
      higher than that of the fish from T75, T100 and T125. Significantly lower amounts
      of carcass lipid and carbohydrate contents were found in T125 compared to the
      contents of the T50, T75 and T100 fish. CONCLUSIONS: Based on the growth
      performance and feed efficiency, the T50 fish m-3 of O. vittatus in a synthetic
      sheet pond may be technically feasible.

PMID- 30187727
TI  - Seed Germination and Seedling Characteristic of <I>ipomoea</I> and <I>Merremia
      </I>(Convolvulaceae) in Lambayeque (Peru).
AB  - BACKGROUND AND OBJECTIVE: Studies were undertaken to determine the effects of in
      vivo germination of mechanically scarified with and without sandpaper, chemically
      scarified with H2SO4 for 40 min and without H2SO4 and in vitro germinated with
      sandpaper and with sandpaper and GA3 seeds of ipomoea and Merremia in the
      Lambayeque region and surrounding areas (Peru). MATERIALS AND METHODS: Seeds of
      16 species of ipomoea and 3 species of Merremia collected from Lambayeque (Peru)
      were germinated under in vivo and in vitro conditions and measured the angle of
      divergence of seedlings and the data were analysed by ANOVA. RESULTS: in the in
      vivo germination process, mechanical and chemical scarification caused an
      increase in germination and in the in vitro germination process mechanical
      scarification with sandpaper and GA3 also caused an increase in germination.
      Seedling emergence was observed and recorded and found not to fit the classical
      models of hypogeal and epigeal emergence and in the seedling morphology the
      degree of apical cleft of paracotyledonary leaves and the angle of divergence
      between the two lobes of a paracotyledon were determined. The length of the
      apical cleft was highly correlated (r = 0.81) with the angle of divergence.
      CONCLUSION: Convolvulaceae is the most advanced family that produces seeds with
      physical dormancy (water-impermeable seed coat).

PMID- 30187728
TI  - Relationship Between Body Composition and Smoking Habit with Telomere Length of
      Minangkabau Ethnicity Men, in West Sumatera, Indonesia.
AB  - BACKGROUND AND OBJECTIVE: An increase in body composition and smoking habit are
      risk factors for high free radical levels in the body. This can lead to oxidative
      stress, due to the imbalance of pro-oxidants and oxidants in the body that leads
      to telomere shortening. The purpose of this research was to investigate the
      correlation between body composition and smoking habit with telomere length of
      men in West Sumatera, Indonesia. MATERIALS AND METHODS: This cross-sectional
      study was conducted in Padang City using a sample of 130 Minangkabau ethnic
      district civil servant men aged between 40-50 years. The smoking habit were
      collected using a questionnaire, body composition data with bioelectrical
      impedance analysis (BIA) and blood sample analysis using O'Callaghan and Fenech's
      technique to measure telomere length. RESULTS: This research indicated an average
      telomere length was 580.37+/-323.58 bp, BMI was 25.01+/-4.15 and percentage body
      fat was 22.06+/-6.16%. The proportion of subjects who smoke is 58.5% with heavy
      smoker 26.3%. The average length of smoked cigarettes was 25.2+/-7.3 years and
      the average of cigarette consumption is 270.58+/-343.18. There were no
      correlations between BMI and body fat percentage with telomere length (p>0.005).
      There is a negative correlation were significantly between smoking duration with
      telomere length (r = -0.270, p = 0.020). Telomere loss was 94.39 bp throughout
      the life-span equivalent to losing 3.4-3.8 years. CONCLUSION: Body composition is
      not a risk factor but smoking duration is a risk factor for telomere shortening
      in ethnic Minangkabau men.

PMID- 30187729
TI  - Lowering Chitin Content of Cricket (<I>Gryllus assimilis</I>) Through Exoskeleton
      Removal and Chemical Extraction and its Utilization as a Ruminant Feed <I>in
      vitro</I>.
AB  - BACKGROUND AND OBJECTIVE: Cricket contains high crude protein level but it also
      contains considerable amount of chitin that may impede nutrient digestion and
      decrease production performance of animal. This experiment aimed to decrease
      chitin content of cricket (C) through exoskeleton removal (CER) or by chemical
      extraction (CCE). MATERIALS AND METHODS: Nutritional evaluation of cricket was
      performed in two experiments. In experiment 1, three forms of cricket were
      prepared, i.e., C, CER and CCE. These were subjected to chemical composition
      determination and in vitro rumen fermentation incubation as individual
      substrates. In experiment 2, C and CER were included in concentrate rations at
      different proportions to substitute soybean meal (SBM), i.e., R1 (concentrate
      containing 30% SBM), R2 (50% SBM was substituted by C), R3 (100% SBM was replaced
      by C) and R4 (100% SBM was replaced by CER). The concentrates were then evaluated
      in vitro for their rumen fermentation and digestibility characteristics. Data
      were analyzed with analysis of variance and Duncan's test. RESULTS: Cricket was
      high in crude protein(CP), ether extract (EE) and chitin contents. Removal of
      exoskeleton decreased CP and chitin contents of cricket. Chemical extraction of
      cricket increased its CP and completely removed its chitin. Main fatty acids
      observed in cricket were linoleic acid, palmitic acid, oleic acid and stearic
      acid and the composition was unaltered due to exoskeleton removal or chemical
      extraction. Cricket was relatively highly digestible and exoskeleton removal and
      chemical extraction did not further improve in vitro dry matter digestibility
      (IVDMD) and in vitro organic matter digestibility (IVOMD) of cricket. The R1 and
      R2 revealed similar IVDMD and IVOMD, but R3 and R4 resulted in lower values for
      both parameters than those of R1 and R2 (p<0.05). CONCLUSION: Exoskeleton removal
      or chemical extraction effectively reduced chitin content of cricket and the
      insect may be used to substitute SBM up to 50% in concentrate for ruminant.

PMID- 30187730
TI  - Morpho-physiological Changes of Biodiesel Producer Plants <I>Reutealis
      trisperma</I> (Blanco) in Response to Gold-Mining Wastewater.
AB  - BACKGROUND AND OBJECTIVE: Reutealis trisperma (Blanco) is a non-edible biodiesel
      producer plant that has a good prospect due to the higher seed production
      capacity and oil content. In addition, it also able to grow well under
      unfavourable environment. The study aimed to analyze the response of Reutealis
      trisperma (R. trisperma) to gold mined wastewater. MATERIALS AND METHODS: Five
      varieties of R. trisperma i.e., Kemiri Minyak-1 (KM1), Kemiri Minyak-2 (KM2),
      Kermindo-1 (KD1), Kermindo-2 (KD2) and Harapan (HR) grown in water culture, were
      treated with wastewater from gold mining industry with concentration of 0, 125,
      250, 500 and 1000 mL for 2 weeks. Shoot and root growth, anatomy as well as some
      physiological characters were analyzed during the treatment. RESULTS: Wastewater
      treatments for 14 days caused decrease of shoot growth and induced leaf yellowing
      of the plants. The treatments caused increase in malondialdehyde content up to 4
      fold, while chlorophyll a, chlorophyll b and total chlorophyll of the plants
      decreased significantly. TEM analysis indicated that the root cell of plants
      exposed to highest concentration of wastewater started to degenerate and had
      higher number of mitochondria and peroxisome vesicles suggesting that the
      cellular respiration and anti-oxidative mechanism presumably became more active
      due to the accumulation of reactive oxygen species. CONCLUSION: Gold mine
      wastewater treatment caused all the plants to undergo stress characterized by the
      increase of malondialdehyde and the decrease of chlorophyll content and leaf
      growth of R. trisperma, even though there was variation among the varieties. KM2
      and KD2 had the best performance among all varieties in response to gold-mine
      wastewater.

PMID- 30187731
TI  - Effect of pH and Temperature on <I>Bacillus subtilis</I> FNCC 0059 Oxalate
      Decarboxylase Activity.
AB  - BACKGROUND AND OBJECTIVE: Bacillus subtilis is a bacterium that can produce the
      oxalate decarboxylase (ODC) enzyme. This enzyme decomposes oxalate. ODC enzyme
      activity is influenced by temperature and pH. This study was conducted to
      determine the optimum pH and temperature for ODC enzyme activity in B. subtilis
      FNCC 0059. MATERIALS AND METHODS: B. subtilis was cultivated in oxalate medium at
      different incubation temperatures for 24 h. The tested temperatures were 25, 29,
      33, 37, 41 and 45 degrees C. In separate experiments, cultures were grown in
      oxalate medium at varying pH from 4-8.5. The cell growth assay and enzyme
      activity were performed and all the experiments were done with 3 replicates. Data
      were analyzed using one-way analysis of variance. RESULTS: The optimum
      temperature of 37 degrees C could produce maximum ODC enzyme activity (0.041 U mL
      1) enzyme activity increased to the point of the optimum pH and then decreased
      5.6% when the pH was increased 0.5 from the optimum. Maximum ODC enzyme activity
      (0.0413 U mL-1) was achieved at pH 5.5. CONCLUSION: Temperature and the pH of the
      medium affected ODC enzyme activity. Optimum medium condition of B. subtilis was
      reached at 37 degrees C and pH 5.5.

PMID- 30187732
TI  - Glutathione-S-transferase, Superoxide Dismutase (GST, SOD) Levels, Protein
      Content and Lipid Peroxidation in <I>Schizothorax plagiostomus </I>under the
      Infection of <I>Pomphorhynchus </I>in Nallah Sukhnag of Kashmir Valley.
AB  - BACKGROUND AND OBJECTIVE: Presence of parasites in fishes has been reported to
      severely damage the status of antioxidants in them. Among helminth parasites,
      Pomphorhyncus an acanthocephalan parasite is commonly found in Schizothorax fish
      of Kashmir and is causing a considerable damage to fish health. The aim of this
      study was to investigate the antioxidant status in muscle, intestine and liver
      tissues of Schizothorax plagiostomus parasitized by Pomphorhyncus. MATERIALS AND
      METHODS: For this, 9 fish specimens collected from Nallah Sukhnag (Budgam) were
      found to be infected only with Pomphorhyncus, an acanthocephalan parasite. Fishes
      having the infection of Pomphorhynchus and the same number of uninfected ones
      were then analyzed for enzymatic antioxidants. Lipid peroxidation and protein
      content was also assayed for both infected and uninfected fishes. Statistically
      the whole data were represented as mean and standard deviation. RESULTS: RESULTS
      showed the reduction of glutathione-s-transferase (GST), superoxide dismutase
      (SOD), protein content while increase in lipid peroxidation in infected muscle,
      intestine and liver tissues as compared to respective organs of the uninfected
      fishes. CONCLUSION: This study concluded that parasitic infections induce
      oxidative stress.

PMID- 30187733
TI  - Simple Sequence Repeat (SSR) and Single Nucleotide Polymorphism (SNP) Markers for
      Genetic Characterization of North Sulawesi Local Rice Varieties, Super Win and
      Burungan.
AB  - BACKGROUND AND OBJECTIVE: The genetic character of North Sulawesi's local rice
      cultivated by local communities has not been extensively explored. Genetic
      character can be used as tool for rice varieties identification to complement the
      morphological characters. This study aimed at developing genetic character of
      North Sulawesi's local rice varieties Burungan and Super Win using SSR and SNP
      molecular markers. MATERIALS AND METHODS: Two local North Sulawesi varieties of
      rice from Bolaang Mongondow Regency, namely Super Win (Tropical Japonica) and
      Burungan (Japonica), were used. Control varieties included in this research were
      IR64 (Indica), Nipponbare (Japonica), Super Win Aromatik (Tropical Japonica) and
      Leukat Hitam (Tropical Japonica). The significant markers associated with agro
      morphological characters were used, such as flowering date, panicle length, flag
      leaf corner, leaf length, panicle branches and the number of productive tillers.
      The SSR and SNP 384-chip which are mapped in the entire rice genome were
      employed. RESULTS: The study showed that Burungan has alleles' size range 108.7
      148.8 with a mean size of alleles 118.97. The frequency of this allele is 33.33%.
      Alleles' size range of Super Win is 109.2-148.8 with a mean size of alleles
      119.50. The frequency of this allele is 22.22%. This diversity variation of
      allele size cannot be used as a genetic identifier for both varieties. The
      genetic distance between Burungan and Super Win varieties was quite high (0.461).
      It was due to they came from different sub species, Burungan was from Japonica
      while Super Win was from Tropical Japonica. CONCLUSION: Burungan and Super Win
      varieties are not a local rice of North Sulawesi.

PMID- 30187734
TI  - Effect of Different Hormonal Treatment on Stevia (<I>rebaudiana </I>Bertoni)
      Micro-propagation.
AB  - BACKGROUND AND OBJECTIVE: Stevia micro propagation method is an extensive and
      highly potential in vitro method use to accelerate plant propagation in compare
      to the other propagation methods. This study tried to examine the effect of
      different hormonal combinations for shoot and root development of stevia plant.
      MATERIALS AND METHODS: In order to identify the best hormonal combination of
      establishment culture, three different media (MS1, MS2 and MS3) combine with
      three separate hormonal combinations for each were tested. For the proliferation
      and rooting culture, a media (MS2) combined with different hormonal combinations
      with different levels were tested. The experiment was conducted as a completely
      randomized design with eight replicates in establishment experiment and factorial
      in base of completely randomized design with four replicates in proliferation and
      rooting experiment. Data was analyzed by one-way analysis of variance using SAS.
      RESULTS: The mean comparison data showed the lowest amount of kinetin and IBA
      added in selected medium from establishment phase (MS2) was more effective in
      proliferation traits. The highest number of lateral branches was observed in the
      IBA 0.25 mg L-1 (3.96) and kinetin 1 mg L-1 (3.91). The mean comparison of
      naphthalene acetic acid and IBA treatments in rooting study confirmed that the
      control treatment (no added NAA and IBA) had the maximum effect on the traits
      studied. The longest root length (1.68 cm) was observed in the control treatment
      culture. CONCLUSION: The Stevia (rebaudiana Bertoni) in vitro culture under
      effect of hormonal treatments showed a significant improvement on proliferation
      and rooting rate.

PMID- 30187735
TI  - Community Ecology of Metazoan Parasites in Two Species of <I>Mystus</I> from
      River Godavari, Andhra Pradesh, India.
AB  - BACKGROUND AND OBJECTIVE: Fishes of the genus Mystus are the members of Bagridae
      family which occupy an important place in Godavari fishery. Two commonly
      available species, Mystus vittatus Bloch, 1800 and Mystus cavasius Hamilton, 1822
      of River Godavari, Rajahmundry Andhra Pradesh serve as significant hosts for
      metazoa?n parasites. The present study was aimed to ascertain the population
      dynamics, community characteristics and the faunal similarity of the two bagridae
      fishes, Mystus vittatus (n = 116) and Mystus cavasius (n = 94) at both infra and
      component community level during the 2008-2009. MATERIALS AND METHODS: Standard
      statistical analyses were conducted to study the parasitic communities of both
      the fishes. Jaccard's similarity coefficient was used to observe the faunal
      similarity of both the fishes. Various parameters such as Shannon-wiener index
      (H'), evenness (E) and Simpson's diversity indices were applied to the fully
      sampled metazoan infracommunities of both fishes. Mean-variance ratio described
      the distribution patterns of the parasites within the host. The correlation
      coefficient (R) explained the correlation between the standard length of host and
      parasitic abundance for all parasites. The Mann-Whitney U-test was applied to
      both the fishes to observe the influence of host sex on the overall parasitic
      abundance. Jaccard's interspecific association was used to find out the
      interspecific association between each pair of parasite species within a same
      host. RESULTS: A total of nine metazoan parasites were obtained from both the
      fishes during the research study. The present investigation includes five
      species, i.e., Haplorchoides macrones, Bifurcohaptor indicus, Thaparocleidus
      tengra, Raosentis podderi and Raosentis thapari that are common to both the
      species. On the other hand, Metacercaria Isoparorchis hypselobagri, Raosentis
      godavarensis and Argulus striatus occurred specifically in Mystus vittatus and
      Lamproglena hospetensis occur exclusively from Mystus cavasius. There were no
      core and secondary species in the parasitic communities of both the fishes. Host
      length and rate of parasitisation showed very less correlation. There was no
      influence of sex on the parasitisation. Over-dispersed distribution is the
      generalized pattern of distribution of macroparasites and all the parasites
      showed over-dispersed distribution patterns except Argulus striatus, which
      displayed a random distribution pattern. The higher JI values indicate that there
      is very less competition among species as they occupy different niches within the
      same host. CONCLUSION: Though, the faunal similarity of both the fishes was high
      but the parasitic communities of these fishes are less diverse, depauperate and
      non-interactive.

PMID- 30187736
TI  - Identification and Management Challenges Associated with <I>Ralstonia
      solanacearum </I> (Smith), Causal Agent of Bacterial Wilt Disease of Tomato in
      Sub-Saharan Africa.
AB  - Tomato is the world's most consumed vegetable crop after potato and it is source
      of vitamins, minerals, fiber, lycopene, beta-carotene and income. Despite its
      significant importance tomato can heavily be attacked by different pathogens
      including Ralstonia solanacearum that incites bacteria wilt disease. The disease
      is very devastating causing a considerable yield loss worldwide. The pathogen can
      survive in plant debris, infected plants and host weeds and spread from one field
      to another by irrigation or flood water, soil, farm equipment and workers and
      weeds which usually grow along waterways and it is difficult to manage due to
      complication in biology, nature of infestation and wide host range. In areas like
      the Sub-Saharan Africa where there exists a wide diversity of plant species, the
      pathogen becomes even more difficult to manage. It is on this basis that this
      review article, clearly discusses challenges for bacterial wilt disease
      identification and management in tomato farming systems with respect to the
      diagnosis methods used, pathogen genetic diversity and host range and pathogen
      survival mechanisms under different environment. The information will empower the
      responsible personnel involved in tomato production chain to have clear
      information about the pathogen and management options available against the
      disease in Sub-Saharan Africa.

PMID- 30187737
TI  - Quality Evaluation of Bakasang Processed with Variation of Salt Concentration,
      Temperature and Fermentation Time.
AB  - BACKGROUND AND OBJECTIVE: Production of bakasang in North Sulawesi has not been
      standardized. Local people still produce it without considering the optimal
      conditions and the fermentation is done in a simple way. The fish viscera is
      traditionally fermented inside a bottle with addition of salt and incubated under
      the sun for a few days until it turns into a liquid. In this present study, the
      quality of bakasang was assessed during various fermentation condition. MATERIALS
      AND METHODS: The viscera of fresh cakalang (Katsuwonus pelamis) fish was
      fermented under various temperatures (30, 50 and 70 degrees C) for 5, 10 and 15
      days with the addition of 10, 20 and 30% of salt. The property of quality
      included pH, moisture content, free fatty acid (FFA) and thiobarbituric acid
      (TBA) of the bakasang product. RESULTS: The results of this study indicated that
      moisture content ranged from 16.42-77.98%. Moisture content decreased with
      increasing the salinity, fermentation temperature and fermentation time. The pH
      of bakasang ranged from 5.66-6.73. The pH of bakasang decreased with the
      increasing salinity. The FFA level ranged from 1.42-5.18, it increased with
      increasing fermentation time but decreased with increasing fermentation
      temperature and increased salt level. The TBA (expressed in malondialdehyde/MDA)
      level varied from 0.53-4.81 g/100 g, it decreased with increasing salinity and
      fermentation temperature but decreased with increasing fermentation time.
      CONCLUSION: The data revealed that based on the property of quality, the best
      product was bakasang produced using salt 20-30% at 70 degrees C which was
      fermented for 15 days.

PMID- 30187738
TI  - Possible Protective Role of Parsley Extract on the Diabetic Pregnant Rats and
      Their Fetuses.
AB  - BACKGROUND AND OBJECTIVE: Gestational diabetes mellitus (GDM) is one form of
      diabetes. It causes obstetrical complications and affects between 5-18% of all
      pregnancies and leads to congenital malformations and long-term postnatal
      disorders. Supportive therapy in treatment of diabetes during pregnancy takes
      place by anti-diabetic plants such as parsley. The current study has been
      undertaken to investigate the possible anti-diabetic and antioxidant role of
      aqueous parsley extract on streptozotocin (STZ) induced gestational diabetes
      mellitus in rats. MATERIALS AND METHODS: Fifty pregnant albino rats were
      categorized after mating into five groups: group C (control group), group D1
      (pregnant rats injected with interperitoneally single dose of STZ (40 mg kg-1
      b.wt.) in the 1st day of gestation, group D1+P: Pregnant rats were treated with
      parsley extract (1 m/150 g b.wt.) from the 1st to the 19th day of gestation post
      injection with STZ (40 mg kg-1 b.wt.), group D7: Pregnant rats were injected with
      STZ (40 mg kg-1 b.wt.) on day 7of gestation, group D7+P: Pregnant rats were
      treated with parsley extract (1 m/150 g b.wt.) from the 7th to the 19th day of
      gestation post injection with STZ (40 mg kg-1 b.wt.). The pregnant rats were
      dissected on the 19th day of pregnancy and the uterine horns were removed freshly
      and then photographed. Abnormalities or any morphological changes were recorded,
      weight of fetuses and placenta and placental index were determined. Blood samples
      were collected to estimate the glucose and biochemical parameters of the main
      kidney functions. Also, kidney samples of fetuses were taken for the
      histopathological study. RESULTS: Fetuses of the diabetic mothers showed some
      developmental changes such as very thin skin, very thin muscle layer under the
      skin, absence of eyelid and ear pinna, exencephaly and kyphosis. On the other
      hand, fetuses of the diabetic mothers which were treated with parsley leaves
      extract showed somewhat normal morphological development. According to the
      biochemical histopathological observations, the parsley leaf extract succeeded to
      minimize the drastic changes, which were observed in the diabetic rats and their
      fetuses. CONCLUSION: Administration of the parsley leaf extract has the ability
      to minimize the damage of hyperglycemia.

PMID- 30187739
TI  - Persistency and Seed Breaking Dormancy on Local Upland Rice of Southeast
      Sulawesi, Indonesia.
AB  - BACKGROUND AND OBJECTIVE: Rice (Oryza sativa L.) is a very important food crop in
      Indonesia. The development of upland rice becomes an alternative solution to meet
      the national rice needs. Upland rice productivity is lower than wetland rice, one
      of the causes is the use of low-vigor seeds. The seeds derived from previous
      harvest seed and newly harvested rice seedlings have physiological dormancy.
      Physiological dormancy relates to seed persistency. The study aimed to evaluate
      the persistence and development of invigoration technique to break seed dormancy
      of upland rice. MATERIALS AND METHODS: The research was conducted at the Agronomy
      Laboratory, Faculty of Agriculture, Halu Oleo University. Research was arranged
      in a completely randomized design (CRD) consisting of 6 treatments namely: A0
      (without treatment), A1 (KNO3 1%), A2 (ground brick matri-conditioning+Bacillus
      sp., CKD061), A3 (ground burned-rice husk matri-conditioning+Bacillus sp.,
      CKD061), A4 (ground brick matri-conditioning+Bacillus sp., CKD061+KNO3 1%) and A5
      (ground burned-rice husk matri-conditioning+Bacillus sp., CKD061+KNO3 1%).
      RESULTS: The results showed that upland rice cultivars from Southeast Sulawesi
      have varying dormancy. The persistence of seed dormancy evaluated are Pae Parigi
      2 is 8 weeks, Pae Parigi 1 is 9 weeks, Pae Kulibungka is 10 weeks, Pae Masaraha
      is 12 weeks and Pae Rowu is 16 weeks. CONCLUSION: Application of seed bio
      invigoration treatment was able to break seed dormancy of local upland rice of
      cv. Pae Parigi 2 with the best treatment was using KNO3 1%+ground brick+Bacillus
      sp., CKD061.

PMID- 30187740
TI  - Antimicrobial Activity and Phytochemical Screening of Sarcocolla Gum Resin.
AB  - BACKGROUND AND OBJECTIVE: Searching for a new antimicrobial agent is a
      significant challenge because of increasing resistance of microbes to
      antibiotics. Because plants are an inexpensive source of rich metabolic
      substances that are highly efficient, this study was designed to evaluate the
      antimicrobial activity of Sarcocolla gum resin extracted from Astragalus
      sarcocolla root and its phytochemicals. To the best of the author's knowledge,
      the antimicrobial activity of Sarcocolla gum resin has not previously been
      reported. MATERIALS AND METHODS: The antimicrobial activity of Sarcocolla gum
      resin was evaluated using a well diffusion assay. The effect of water and ethanol
      extracts in various concentrations (20, 40 and 60%) against the growth of
      pathogenic bacteria and yeast were tested. RESULTS: The results showed that the
      lower concentration (20%) of water and ethanol extracts had no inhibitory effect
      on any of the tested microbes except Staphylococcus aureus (S. aureus) ATCC
      29213. However, an antimicrobial effect of water and ethanol extracts was
      observed on most tested microbes at higher concentrations (40 and 60%). The S.
      aureus ATCC 29213 was resistant to all ethanol extract concentrations. In
      contrast, S. aureus ATCC 29213 was inhibited by water extracts at all
      concentrations tested. Minimum inhibitory concentrations (MIC) were estimated
      using a 2-fold dilution method and MIC values were between 12.5-25 MUg mL-1.
      Phytochemical screening was performed using standard procedures that showed the
      presence of sterols, terpenoids, flavonoids, alkaloids, saponins and tannins.
      CONCLUSION: This study showed that Sarcocolla gum resin extract possesses high
      antimicrobial activity that depends on the solvent type, the concentration of
      plant extract and the microbe type. These results provide a new source of
      antimicrobial that may be useful in the manufacture of antibiotics.

PMID- 30187741
TI  - Study of Genetic Diversity on Six Species of Indonesian <I>Coelogyne</I> spp.
      Based on ISSR Markers.
AB  - BACKGROUND AND OBJECTIVE: Almost all of Coelogyne species from Indonesia are
      epiphytic. Some of these are facing the extincion and need to be conserved
      through plant breeding programs. Unfortunately, there are not many research
      reports on the genetic diversity of orchids which are substantial for genetic
      conservation and plant breeding program. The study aimed to identify the genetic
      diversity of some important species of genus Coelogyne spp., performed using
      inter simple sequence repeats (ISSR) molecular marker. MATERIALS AND METHODS: The
      DNA of six orchid species from the genus of Coleogyne spp. was separated and
      served as samples in the PCR amplification reaction using 10 ISSR primers.
      RESULTS: This study found that using six orchid species from the genus of
      Coelogyne spp. (C. pandurata, C. massangeana, C. mayeriana, C. asperata, C.
      celebensis and C. rumphii ), the ISSR primers yielded as many as 106 amplified
      fragments which varied in size from 250-3000 bp. CONCLUSION: Moreover, this study
      showed that the polymorphic amplification bands reached as high as 98.9% and the
      similarity coefficient of the six orchid species studied revolved between 0.32
      0.70, meaning that the genetic diversity of the orchid species studied was spread
      out between 0.30-0.68.

PMID- 30187742
TI  - Finding the stories: a novice qualitative researcher learns to analyse narrative
      inquiry data.
AB  - BACKGROUND: Qualitative research skills, especially those used in narrative
      inquiry, are challenging to develop. While the literature provides guidance on
      some techniques, such as collecting data, few authors share the complex process
      of data analysis. AIM: To offer a possible road map for novice researchers
      learning to analyse data generated by narrative inquiry. DISCUSSION: The author
      describes how a novice qualitative researcher analysed data collected using
      narrative inquiry with nursing students who failed and then repeated a course.
      This article shares a step-by-step explanation of how data were analysed,
      including using qualitative data analysis software to manage the data.
      CONCLUSION: The process of analysing qualitative data is ill-defined, with great
      variability among researchers and methodologies. It can be valuable for novice
      researchers to consider the experiences of others when planning their analysis.

PMID- 30187743
TI  - Highly Stable In-Plane Microwave Magnetism in Flexible Li0.35Zn0.3Fe2.35O4(111)
      Epitaxial Thin Films for Wearable Devices.
AB  - With the advances in artificial intelligence and communication technologies,
      flexible microwave magnetic materials have become essential for flexible
      microwave detectors, wearable microwave sensors, and flexible spintronics. Here,
      a highly stable in-plane (IP) ferromagnetic resonance (FMR) and a tunable out-of
      plane (OOP) FMR character are demonstrated in the flexible microwave magnetic
      Li0.35Zn0.3Fe2.35O4 (LZFO) (111) epitaxial thin films under external mechanical
      bending. Both the IP FMR line width and resonance field ( Hr) are basically
      unchanged when the sample was bent under an external tensile or compressive
      bending strain and deformation. However, the OOP FMR spectra (including Hr and
      absorption peak) could be tuned by mechanical bending, i.e., the LZFO sample
      possesses two OOP FMR absorption peaks at an external bending curvature.
      Meanwhile, excellent mechanical antifatigue and mechanical retention
      characteristics have also been obtained in the LZFO sample. The highly stable IP
      and the tunable OOP FMR spectra in the same LZFO sample with excellent mechanical
      antifatigue character have a promising prospect in microwave magnetic devices and
      flexible spintronics.

PMID- 30187744
TI  - Surfactant-Free Interface Suspended Gold Graphitic Surface-Enhanced Raman
      Spectroscopy Substrate for Simultaneous Multiphase Analysis.
AB  - Simultaneous multiphase detection of multiplex analytes is important, albeit
      challenging, especially in pharmaceuticals analysis since drugs with lipid and
      water solubility were often administrated together for synergistic therapy.
      Surface-enhanced Raman spectroscopy (SERS) is a label-free and sensitive tool for
      multiplex analytes detection at multiphase interfaces. However, the requirements
      of inducers or surfactant surface modification of the SERS substrate have
      restricted extensive applications. Herein, we developed a graphene-isolated-Au
      nanocrystal based multiphase analysis system. Unexpectedly, the gold graphitic
      SERS substrate can simply suspend at the interface of the different phase without
      the involvement of any surfactant. Therefore, the proximity of substrate with
      analyte molecules remains unaffected. Such suspended substrate not only ensures
      sensitive SERS detection but also enables the enrichment of analytes from the
      different phase simultaneously without interference. Moreover, the graphitic
      shell of the SERS substrate has a unique vibration band located in the Raman
      biological silence region which is utilized as the internal standard and improves
      the SERS quantification accuracy. Efficient ex vivo multiphase enrichment and
      detection of mimic lipid- and water-soluble drugs injected into mice were
      demonstrated with such gold graphitic substrate, showing the potential of this
      simultaneous multiplex pharmacokinetic analysis.

PMID- 30187745
TI  - Monitoring Local Electric Fields at Electrode Surfaces Using Surface Enhanced
      Raman Scattering-Based Stark-Shift Spectroscopy during Hydrogen Evolution
      Reactions.
AB  - We report the use of surface-enhanced Raman scattering (SERS) to measure the
      vibrational Stark shifts of surface-bound thiolated-benzonitrile molecules bound
      to an electrode surface during hydrogen evolution reactions (HERs). Here, the
      electrode surface consists of Au nanoislands deposited both with and without an
      underlying layer of monolayer graphene on a glass substrate. The Stark shifts
      observed in the nitrile (C-N) stretch frequency (around 2225 cm-1) are used to
      report the local electric field strength at the electrode surface under
      electrochemical working conditions. Under positive (i.e., oxidative) applied
      potentials [vs normal hydrogen electrode (NHE)], we observe blue shifts of up to
      7.6 cm-1, which correspond to local electric fields of 22 mV/cm. Under negative
      applied potentials (vs NHE), the C-N stretch frequency is red-shifted by only
      about 1 cm-1. This corresponds to a regime in which the electrochemical current
      increases exponentially in the hydrogen evolution process. Under these finite
      electrochemical currents, we estimate the voltage drop across the solution ( V =
      IR). Correcting for this voltage drop results in a highly linear electric field
      versus applied electrochemical voltage relation. Here, the onset potential for
      the HER lies around 0.2 V versus NHE and the point of zero charge (PZC) occurs at
      0.04 V versus NHE, based on the capacitance-voltage ( C- V) profile. The solution
      field is obtained by comparing the C-N stretch frequency in solution with that
      obtained in air. By evaluating the local electric field strength at the PZC and
      the onset potential, we can separate the solution field from the reaction field
      (i.e., electrode field), respectively. At the onset of HER, the solution field is
      -0.8 mV/cm and the electrode field is -1.2 mV/cm. At higher ion concentrations,
      we observe similar electric field strengths and more linear E-field versus
      applied potential behavior because of the relatively low resistance of the
      solution, which results in negligible voltage drops ( V = IR).

PMID- 30187746
TI  - Accelerated Oxidation of Organic Contaminants by Ferrate(VI): The Overlooked Role
      of Reducing Additives.
AB  - This paper presents an accelerated ferrate(VI) (FeVIO42-, FeVI) oxidation of
      contaminants in 30 s by adding one-electron and two-electron transfer reductants
      (R(1) and R(2)). An addition of R(2) (e.g., NH2OH, AsIII, SeIV, PIII, and NO2-,
      and S2O32-) results in FeIV initially, while FeV is generated with the addition
      of R(1) (e.g., SO32-). R(2) additives, except S2O32-, show the enhanced oxidation
      of 20-40% of target contaminant, trimethoprim (TMP). Comparatively, enhanced
      oxidation of TMP was up to 100% with the addition of R(1) to FeVI. Interestingly,
      addition of S2O32- (i.e., R(2)) also achieves the enhanced oxidation to 100%.
      Removal efficiency of TMP depends on the molar ratio ([R(1)]:[FeVI] or
      [R(2)]:[FeVI]). Most of the reductants have the highest removal at molar ratio of
      ~0.125. A FeVI-S2O32- system also oxidizes rapidly a wide range of organic
      contaminants (pharmaceuticals, pesticides, artificial sweetener, and X-ray
      contrast media) in water and real water matrices. FeV and FeIV as the oxidative
      species in the FeVI-S2O32--contaminant system are elucidated by determining
      removal of contaminants in oxygenated and deoxygenated water, applying probing
      agent, and identifying oxidized products of TMP and sulfadimethoxine (SDM) by
      FeVI-S2O32- systems. Significantly, elimination of SO2 from sulfonamide (i.e.,
      SDM) is observed for the first time.

PMID- 30187747
TI  - 1,3-Dioxolane-4-ol Hemiacetal Stores Formaldehyde and Glycolaldehyde in the Gas
      Phase.
AB  - We report the spontaneous gas-phase formation of 1,3-dioxolane-4-ol, a mixed
      hemiacetal resulting from the addition of glycolaldehyde to formaldehyde. It was
      spectroscopically characterized by matching matrix IR spectra with coupled
      cluster computations. The formation of the hemiacetal must be surface-catalyzed
      owing to the very high computed reaction barrier of 39.8 kcal mol-1. The reaction
      barrier is lowered by almost 20 kcal mol-1 when a single water molecule acts as a
      proton shuttle in a favorable six-membered transition state. We characterized the
      hemiacetal in solution via NMR spectroscopy and followed its decomposition into
      its constituents within a few hours; it also dissociates upon contact with water.
      Sugars form in the presence of Ca(OH)2, in line with formose-type reactivity. 1,3
      Dioxolane-4-ol may be considered a storage form for formaldehyde and
      glycolaldehyde that is rather stable in the gas-phase.

PMID- 30187748
TI  - Highly Efficient Thermally Activated Delayed Fluorescence Organic Light-Emitting
      Diodes with Fully Solution-Processed Organic Multilayered Architecture: Impact of
      Terminal Substitution on Carbazole-Benzophenone Dendrimer and Interfacial
      Engineering.
AB  - A series of second-generation carbazole-benzophenone dendrimer substituted by
      several functional groups at terminal positions (subG2B) was investigated toward
      a thermally activated delayed fluorescence (TADF) emitter for nondoped emissive
      layer (EML) application in a solution-processed organic light-emitting diode
      (OLED). Substitution was found to dramatically alter the photophysical properties
      of the dendritic TADF emitters. The introduction of tert-butyl and phenyl group
      endows the subG2Bs with aggregation-induced emission enhancement character by
      suppression of internal conversion in singlet excited states. In the meantime,
      the introduction of a methoxy group resulted in aggregation-caused quenching
      character. The device performance of the OLED, where subG2B neat films were
      incorporated as nondoped EMLs, was found to be highly enhanced by adopting fully
      solution-processed organic multilayer architecture in comparison to the devices
      with a vacuum-deposited electron transporting layer (ETL), achieving a maximum
      external quantum efficiency of 17.0%. Such improvement was attributable to the
      improved carrier balance via intermixing at solution-processed EML/ETL
      interfaces. It was also found that the post-thermal annealing of the OLED at
      appropriate temperatures could be beneficial to enhance OLED performance by
      promoting the intermixing EML/ETL interface to some extent. Our findings
      emphasize the potential utility of dendritic TADF emitters in the solution
      processed TADF-OLED and increase the importance to manipulate dendrimer/small
      molecule interfaces.

PMID- 30187749
TI  - Synergistic Effect of a Thermal Reaction and Vacuum Dehydration on Improving
      Xylose-Phenylalanine Conversion to N-(1-Deoxy-d-xylulos-1-yl)-phenylalanine
      during an Aqueous Maillard Reaction.
AB  - The synergistic effect of a thermal reaction and vacuum dehydration on the
      conversion of xylose (Xyl) and phenylalanine (Phe) to a Maillard-reaction
      intermediate (MRI) was researched. The yield of N-(1-deoxy-alpha-d-xylulos-1-yl)
      phenylalanine was successfully improved and increased from 13.62 to 47.23%
      through the method combining a thermal reaction and vacuum dehydration. A dynamic
      process was involved in the transformation of Xyl and Phe (Xyl-Phe) to N
      substituted d-xylosamine and in the transformation of N-substituted d-xylosamine
      to N-(1-deoxy-alpha-d-xylulos-1-yl)-phenylalanine during the initial stage of
      dehydration; then, only the transformation of N-substituted d-xylosamine to N-(1
      deoxy-alpha-d-xylulos-1-yl)-phenylalanine occurred during the final stage.
      Furthermore, the MRI was prepared under optimized conditions (90  degrees C and
      pH 7.4), and the obtained MRI was characterized and confirmed by ESI mass
      spectrometry and NMR.

PMID- 30187750
TI  - Improvement of the Color Stability of Cyanidin-3-glucoside by Fatty Acid
      Enzymatic Acylation.
AB  - Anthocyanins are water-soluble pigments with limited application in lipophilic
      matrices such as lipid-based foods and cosmetic formulations. In this work, the
      liposolubility improvement of cyanidin-3-glucoside (cy3glc) was performed by
      enzymatic esterification with saturated fatty acids with variable chain lengths,
      and their thermostabilities were evaluated at different pH values in a lipophilic
      medium (an aqueous sodium dodecyl sulfate solution) by means of UV-vis
      spectroscopy. Overall, lipophilic cy3glc derivatives showed improved color
      stability and lowered sensitivity to thermal degradation than nonmodified cy3glc
      in an SDS micellar solution between pH 3 and 7.

PMID- 30187751
TI  - Diphenyl Carbonate: A Highly Reactive and Green Carbonyl Source for the Synthesis
      of Cyclic Carbonates.
AB  - A practical, safe, and highly efficient carbonylation system involving a diphenyl
      carbonate, an organocatalyst, and various diols is presented herein and produces
      highly valuable cyclic carbonates. In reactions with a wide range of diols,
      diphenyl carbonate was activated by bicyclic guanidine 1,5,7
      triazabicyclo[4.4.0]dec-5-ene (TBD) as a catalyst, which successfully replaced
      highly toxic and unstable phosgene or its derivatives while maintaining the
      desired high reactivity. Moreover, this new system can be used to synthesize
      sterically demanding cyclic carbonates such as tetrasubstituted pinacol
      carbonates, which are not accessible via other conventional methods.

PMID- 30187753
TI  - Quantification of Ammonium Phosphatide Emulsifiers in Chocolate Using 31P NMR
      Spectroscopy.
AB  - 31P NMR is a valuable tool to study phosphorus-containing biomolecules from
      complex mixtures. One important group of such molecules are phosphorus-containing
      emulsifiers, including lecithins and ammonium phosphatides (AMPs), which are used
      in chocolate production. By developing extraction protocols and applying high
      resolution 31P nuclear magnetic resonance (NMR), we enable identification of the
      type of emulsifier used in chocolate. We furthermore demonstrate that this method
      allows quantification of AMPs in chocolate. To our knowledge, this is the first
      method that allows verification of the type and amount of emulsifier present in
      chocolate samples.

PMID- 30187752
TI  - Flavor Retention and Release from Beverages: A Kinetic and Thermodynamic
      Perspective.
AB  - For the investigation of retention and release of flavor components, various
      methods are available, which are mostly used on a case-to-case basis depending on
      the raw material. These effects that originate from kinetics and thermodynamics
      could be put in a much wider perspective if these fields were taken as a starting
      point of investigation in combination with rigorous data analysis. In this
      Review, we give an overview of experimental techniques and data analysis methods,
      and predictive methods using mass transfer techniques are also discussed in
      detail. We use this as a foundation to discuss the interactions between volatile
      flavors and the matrix of liquid foods/beverages. Lipids present in the form of
      an emulsion are the strongest volatile retainers due to the lipophilic nature of
      most of the volatile flavors. Proteins also have flavor retention properties,
      whereas carbohydrates hardly have a retention effect in beverages. Smaller
      components, such as sugars and salts, can change the water activity, thereby
      facilitating flavor release. Alternatively, salts can also indirectly affect
      binding sites of proteins leading to release (e.g., NaCl and Na2SO4) or retention
      (NaCSN and Cl3CCOONa) of flavors. Furthermore, the effects of temperature and pH
      are discussed. The Review concludes with a critical section on determination of
      parameters relevant to flavor release. We highlight the importance of accurate
      determination of low concentrations when using linearization methods and also
      show that there is an intrinsic preference for nonlinear regression methods that
      are much less sensitive to measurement error.

PMID- 30187754
TI  - Halogen Migration in Hybrid Perovskites: The Organic Cation Matters.
AB  - In hybrid perovskite materials, the organic cations are one of the key structural
      components used to tune the electronic and optical properties of this promising
      class of materials. Here, we studied the strong impact of organic cations,
      methylammonium (MA) and formamidinium (FA), on halogen vacancy and interstitial
      migration, as well as surface degradation in cubic-phase MAPbBr3 and FAPbBr3
      crystals using density functional theory calculations. We found Br vacancies and
      interstitials have much lower formation energies and higher density in MAPbBr3 in
      comparison to FAPbBr3 crystals. Moreover, the transition energy barrier for Br
      migration through vacancies within the bulk phase is lower in MAPbBr3 than in
      FAPbBr3. We also found that FAPbBr3 has a much higher rotation barrier of the
      organic cation than MAPbBr3, which points to a much stronger H-bonding with Br in
      the former case. Our results show that incorporating organic cations with the
      appropriate structure, shape, and strong H-bonding capabilities in hybrid
      perovskite crystals is very beneficial for suppressing ion migration and thus
      further improving the performance of hybrid perovskite-based devices.

PMID- 30187755
TI  - Detection of CRISPR-dCas9 on DNA with Solid-State Nanopores.
AB  - Solid-state nanopores have emerged as promising platforms for biosensing
      including diagnostics for disease detection. Here we show nanopore experiments
      that detect CRISPR-dCas9, a sequence-specific RNA-guided protein system that
      specifically binds to a target DNA sequence. While CRISPR-Cas9 is acclaimed for
      its gene editing potential, the CRISPR-dCas9 variant employed here does not cut
      DNA but instead remains tightly bound at a user-defined binding site, thus
      providing an excellent target for biosensing. In our nanopore experiments, we
      observe the CRISPR-dCas9 proteins as local spikes that appear on top of the ionic
      current blockade signal of DNA molecules that translocate through the nanopore.
      The proteins exhibit a pronounced blockade signal that allows for facile
      identification of the targeted sequence. Even at the high salt conditions (1 M
      LiCl) required for nanopore experiments, dCas9 proteins are found to remain
      stably bound. The binding position of the target sequence can be read from the
      spike position along the DNA signal. We anticipate applications of this nanopore
      based CRISPR-dCas9 biosensing approach in DNA-typing based diagnostics such as
      quick disease-strain identification, antibiotic-resistance detection, and genome
      typing.

PMID- 30187756
TI  - Near Length-Independent Conductance in Polymethine Molecular Wires.
AB  - Polymethine dyes are linear pi-conjugated compounds with an odd number of carbons
      that display a much greater delocalization in comparison to polyenes that have an
      even number of carbon atoms in their main chain. Herein, we perform scanning
      tunneling microscope based break-junction measurements on a series of three
      cyanine dyes of increasing length. We demonstrate, at the single molecule level,
      that these short chain polymethine systems exhibit a substantially smaller decay
      in conductance with length (attenuation factor beta = 0.04 A-1) compared to
      traditional polyenes (beta ~ 0.2 A-1). Furthermore, we show that by changing
      solvent we are able to shift the beta value, demonstrating a remarkable negative
      beta value, with conductance increasing with molecular length. First principle
      calculations provide support for the experimentally observed near-uniform length
      dependent conductance and further suggest that the variations in beta with
      solvent are due to solvent-induced changes in the alignment of the frontier
      molecular orbitals relative to the Fermi energy of the leads. A simplified Huckel
      model suggests that the smaller decay in conductance correlates with the smaller
      degree of bond order alternation present in polymethine compounds compared to
      polyenes. These findings may enable the design of molecular wires without a
      length-dependent decay for efficient electron transport at the nanoscale.

PMID- 30187757
TI  - Invalidity of Band-Gap Engineering Concept for Bi3+ Heterovalent Doping in
      CsPbBr3 Halide Perovskite.
AB  - Heterovalent CsPbBr3 doping with Bi results in a significant red shift of the
      optical absorption of both single-crystal and powdered samples. The results of
      low-temperature (3.6 K) photoluminescence studies of perovskite single crystals
      indicate that the position of the excitonic luminescence peak remains unaffected
      by Bi doping that, in turn, infers that the band gap of Bi-doped perovskite is
      not changed as well. The position and state density distribution of the valence
      band and Fermi level of single-crystal perovskites were determined by another
      direct method of ultraviolet photoelectron spectroscopy. The obtained results
      show that Bi3+ doping causes no changes in the valence band structure but an
      increase in the Fermi level by 0.6 eV. The summary of the obtained results
      directly demonstrates that the concept of the band-gap engineering in Bi3+-doped
      CsPbBr3 halide perovskite is not valid.

PMID- 30187759
TI  - Total Synthesis of Trisaccharide Repeating Unit of O-Specific Polysaccharide of
      Pseudomonas fluorescens BIM B-582.
AB  - The first total synthesis of the trisaccharide repeating unit of the O-specific
      polysaccharide of Pseudomonas fluorescens BIM B-582 is reported. This efficient
      synthesis involves consecutive 1,2- cis glycosylations including beta-l
      rhamnosylation and alpha selective coupling of rare 4-deoxy-d- xylo-hexose as the
      key steps. The synthetic trisaccharide is equipped with an aminopropyl linker at
      the reducing end to allow for conjugation to proteins and microarrays for further
      immunological studies.

PMID- 30187758
TI  - Hole Transport in Low-Donor-Content Organic Solar Cells.
AB  - Organic solar cells with an electron donor diluted in a fullerene matrix have a
      reduced density of donor-fullerene contacts, resulting in decreased free-carrier
      recombination and increased open-circuit voltages. However, the low donor
      concentration prevents the formation of percolation pathways for holes.
      Notwithstanding, high (>75%) external quantum efficiencies can be reached,
      suggesting an effective hole-transport mechanism. Here, we perform a systematic
      study of the hole mobilities of 18 donors, diluted at ~6 mol % in C60, with
      varying frontier energy level offsets and relaxation energies. We find that hole
      transport between isolated donor molecules occurs by long-range tunneling through
      several fullerene molecules, with the hole mobilities being correlated to the
      relaxation energy of the donor. The transport mechanism presented in this study
      is of general relevance to bulk heterojunction organic solar cells where mixed
      phases of fullerene containing a small fraction of a donor material or vice versa
      are present as well.

PMID- 30187760
TI  - The Study of Laryngoscopic and Autonomic Patterns in Exercise-Induced Laryngeal
      Obstruction.
AB  - OBJECTIVES: (1) Identify laryngeal patterns axiomatic to exercise-induced
      laryngeal obstruction (EILO) and (2) investigate the role of autonomic function
      in EILO. METHODS: Twenty-seven athletic adolescents (13 EILO, 14 control)
      underwent laryngoscopy at rest and exercise. Glottal configurations, supraglottic
      dynamics, systolic blood pressure responses, and heart rate recovery were
      compared between conditions and groups. RESULTS: Inspiratory glottal angles were
      smaller in the EILO group than the control group with exercise. However, group
      differences were not statistically significant ( P > .05), likely due to high
      variability of laryngeal responses in the EILO group. Expiratory glottal patterns
      showed statistically greater abductory responses to exercise in the control group
      ( P = .001) but not the EILO group ( P > .05). Arytenoid prolapse occurred
      variably in both groups. Systolic blood pressure responses to exercise were
      higher in the control group, and heart rate recovery was faster in the EILO
      group. However, no significant differences were seen between the 2 groups on
      either autonomic parameter ( P > .05). CONCLUSIONS: "Paradoxical" inspiratory and
      blunted expiratory vocal fold pattern responses to exercise best characterize
      EILO. Group differences were only seen with exercise challenge, thus highlighting
      the utility of provocation and control groups to identify EILO.

PMID- 30187762
TI  - Comment: Critical Care Pharmacists and Medication Management in an ICU Recovery
      Center.

PMID- 30187761
TI  - Histopathology of the Mucosa of Eustachian Tube Orifice at the Middle Ear in
      Chronic Otitis Media With Effusion: Possible Insight Into Tuboplasty Failure.
AB  - INTRODUCTION: Balloon dilation of the cartilaginous segment of the Eustachian
      tube has emerged as a means to directly augment tubal dilatory function, and this
      has been applied as a potential treatment for otitis media with effusion (OME).
      Although results of clinical studies involving this modality appear promising,
      there are still a moderate number of ears affected by OME that do not respond.
      The purpose of this study was to investigate the status of mucosa of the
      Eustachian tube at the middle ear orifice in OME as it may relate to some cases
      of tuboplasty failure. METHODS: Twenty-three temporal bone specimens with OME
      were identified within an institutional archived collection. Each specimen was
      inspected for the presence of a fixed obstruction at the level of the Eustachian
      tube orifice at the protympanum. In addition, the mucosa at the tubal orifice was
      graded on a 4-point scale. RESULTS: Overall, 3 cases (13%) were normal (Grade 1),
      6 cases (26%) were mildly thickened (Grade 2), 11 (48%) were severely thickened
      (Grade 3), and 3 (13%) were severely thickened with polypoid degeneration (Grade
      4). A single case was noted to have a complete fixed obstruction in the form of a
      mucosal web. CONCLUSION: In ears affected by OME, the mucosa of the Eustachian
      tubal orifice at the middle ear is most often severely thickened. Normal mucosa,
      mucosa with severe polypoid changes, or a complete fixed obstruction are possible
      but uncommon. The majority of specimens studied had sufficiently diseased mucosa
      to raise questions regarding whether thickened mucosa in the tubal orifice may
      act as a barrier to middle ear ventilation that would not be directly addressed
      by cartilaginous Eustachian tube balloon dilation.

PMID- 30187763
TI  - Comment: Safety and Efficacy of Apixaban Versus Warfarin in Patients With
      Advanced Chronic Kidney Disease.

PMID- 30187764
TI  - Does Reinke's Edema Grade Determine Premalignant Potential?
AB  - OBJECTIVE: Reinke's edema (RE) is a benign disease of the vocal folds with a wide
      spectrum of clinical severity. We aim to evaluate the clinical impact of RE grade
      and determine if RE grade correlates with severity of dysplasia and tobacco
      exposure. METHODS: Patients with isolated RE who underwent surgical excision
      between December 2010 and December 2014 were retrospectively reviewed. The RE
      grade was determined from archived laryngeal videostroboscopy exams. Pathologic
      severity of dysplasia, categorized by squamous intraepithelial neoplasia (SIN)
      classification, and tobacco history were extracted from medical records. RESULTS:
      Of 95 lesions, 3 (3.16%) were RE grade 1, 33 (34.74%) were RE grade 2, 24
      (25.26%) were RE grade 3, and 35 (36.84%) were RE grade 4. Fifty-nine lesions
      (62.11%) had no dysplasia (SIN0), 19 (20.00%) had mild dysplasia (SIN1), 15
      (15.79%) had moderate dysplasia (SIN 2), and 2 (2.11%) had severe dysplasia
      (SIN3). The 2 patients with severe dysplasia had grade 4 lesions. No statistical
      correlation was identified between RE grade and the severity of dysplasia.
      Furthermore, no statistical correlation was seen between tobacco exposure and the
      severity of dysplasia or the RE grade. CONCLUSIONS: Size of RE lesion does not
      reflect premalignancy. The majority of RE lesions, regardless of size, have
      little to no premalignant potential. Severe dysplasia/carcinoma in situ may be
      more likely seen in grade 4 lesions; however, the paucity of severe dysplasia
      published in RE data and in this cohort preclude any formal inference. Further
      study of grade 4 lesions is warranted.

PMID- 30187766
TI  - Endothelial Stanniocalcin 1 Maintains Mitochondrial Bioenergetics and Prevents
      Oxidant-Induced Lung Injury via Toll-Like Receptor 4.
AB  - AIMS: Oxidant-induced endothelial injury plays a critical role in the
      pathogenesis of acute lung injury (ALI) and subsequent respiratory failure. Our
      previous studies revealed an endogenous antioxidant and protective pathway in
      lung endothelium mediated by heat shock protein 70 (Hsp70)-toll-like receptor 4
      (TLR4) signaling. However, the downstream effector mechanisms remained unclear.
      Stanniocalcin 1 (STC1) has been reported to mediate antioxidant responses in
      tissues such as the lungs. However, regulators of STC1 expression as well as its
      physiological function in the lungs were unknown. We sought to elucidate the
      relationship between TLR4 and STC1 in hyperoxia-induced lung injury in vitro and
      in vivo and to define the functional role of STC1 expression in lung endothelium.
      RESULTS: We identified significantly decreased STC1 expression in TLR4 knockout
      mouse lungs and primary lung endothelium isolated from TLR4 knockout mice.
      Overexpression of STC1 was associated with endothelial cytoprotection, whereas
      decreased or insufficient expression was associated with increased oxidant
      induced injury and death. An Hsp70-TLR4-NFkappaB signal mediates STC1 induction
      in the lungs and endothelial cells. We also demonstrated a previously
      unrecognized role for mitochondrial-associated STC1, via TLR4, in maintaining
      normal glycolysis, mitochondrial bioenergetics, and mitochondrial calcium levels.
      INNOVATION: To date, a physiological role for STC1 in oxidant-induced ALI has not
      been identified. In addition, our studies show that STC1 is regulated by TLR4 and
      exerts lung and endothelial protection in response to sterile oxidant-induced
      lung injury. CONCLUSIONS: Our studies reveal a novel TLR4-STC1-mediated
      mitochondrial pathway that has homeostatic as well as oxidant-induced
      cytoprotective functions in lung endothelium. Antioxid. Redox Signal. 00, 000
      000.

PMID- 30187765
TI  - Study on Normal Laryngeal Electromyography of Thyroarytenoid Muscle, Cricothyroid
      Muscle, and Posterior Cricoarytenoid Muscle.
AB  - OBJECTIVE: The aim of this study was to investigate the physiological activity of
      intrinsic laryngeal muscle under different functional states of larynx by
      measuring the normal laryngeal electromyography parameters. METHODS: Laryngeal
      electromyography (EMG) was performed in 112 patients with unilateral vocal cord
      movement disorder. The duration and amplitude of the motor unit potential (MUP)
      of the thyroarytenoid muscle (TA), posterior cricoarytenoid muscle (PCA), and
      cricothyroid muscle (CT) were measured when patients were asked to make a deep
      inspiration and phonate /i/. The normal side of the patients' vocal chords was
      used as the research object. RESULTS: (1) The motor unit potential of TA, CT, and
      PCA were measured when inspiration and phonating /i/. Waveforms were normal. (2)
      There were significant differences in duration of TA between inspiration and
      phonating /i/ in comfortable tone. (3) When comparing the duration and amplitude
      of any 2 of TA, CT, and PCA during inspiration and phonating /i/, there were
      significant differences in duration between CT and PCA when phonating /i/ only.
      There were no significant differences in any other comparisons. CONCLUSIONS:
      Under either deep inspiration or pronunciation, the TA, CT, and PCA muscles were
      activated. The TA may play a major role in phonating. The PCA may play a major
      role in the action of deep inspiration.

PMID- 30187767
TI  - Influence of 980-nm Diode Laser Vaporization on Sexual Function: A Short-Term
      Follow-Up Study.
AB  - OBJECTIVE: The aim of this study was to assess changes in sexual function after
      980-nm diode laser vaporization of the prostate. METHODS: A total of 82 benign
      prostatic hyperplasia (BPH) patients underwent 980-nm diode laser vaporization
      from May 2013 to December 2016, and were followed up for 12 months. The following
      outcomes were assessed at baseline, 6, and 12 months postoperatively:
      international prostate symptom score (IPSS), quality of life (QoL) score, maximum
      urinary flow rate (Qmax), five-item version of international index of erectile
      dysfunction questionnaire (IIEF-5), male sexual health questionnaire ejaculatory
      function domain Short Form (MSHQ-EjD Short Form), and retrograde ejaculation.
      RESULTS: Significant improvements at 6 and 12 months were noted postoperatively
      using IPSS, QoL, and Qmax compared with the preoperative values. Considering both
      patients and subgroups, the mean postoperative IIEF-5 scores at 6 and 12 months
      were unchanged compared with baseline. Regarding the MSHQ-EjD Short Form, at 6
      and 12 months follow-up, postoperative total score of ejaculation function was
      decreased because the volume of ejaculation was decreased significantly. The
      frequency of ejaculation and force of ejaculation were also decreased, but the
      difference was not statistically significant. No significant difference in
      ejaculation bother item was observed after the operation. Patients with
      retrograde ejaculation at 6 and 12 months follow-up increased from 6/82 (7.3%) to
      38/82 (46.3%), 42/82 (51.2%). CONCLUSION: The sexual function of patients could
      be maintained after 980-nm diode laser vaporization of prostate with the
      exception of reduction of ejaculatory volume and retrograde ejaculation.

PMID- 30187768
TI  - Mobile Applications for Allergic Rhinitis.
AB  - OBJECTIVE: To study and review the currently available mobile applications
      relating to allergic rhinitis. METHODS: The Apple and Google mobile app stores
      were queried with search terms relating to allergic rhinitis. Apps were assigned
      to categories and analyzed based on description and characteristics such as
      popularity, reviews, cost, platform, and physician involvement in development.
      RESULTS: A total of 72 apps related to allergic rhinitis were identified. Fifty
      four apps were unique, with 18 apps found on both operating systems. Forty
      (55.5%) apps were available in the Apple App store, and 32 (44.4%) apps were
      available in the Google Play app store. They were grouped into the following
      categories: patient education (18; 25%), journals (15; 20.8%), symptom tracking
      (14; 19.4%), clinical/private practice (13; 18.1%), pollen forecast (7; 9.7%),
      medical education (4; 5.6%), and other (1; 1.4%). The majority of apps were free
      of charge (67; 93.1%), with paid apps ranging from $1.47 to $4.99. Apps that were
      reviewed had an average rating of 3.9 out of 5. Physicians were involved in the
      development of 37 (51.4%) apps. CONCLUSIONS: The collection of mobile apps
      developed for allergic rhinitis includes those for both educational and clinical
      use. Mobile apps may have an increasing role in otolaryngic allergy and rhinology
      practices in the future. Thus, continued research is warranted to determine the
      best way to ensure the accuracy and quality of app content as well as the extent
      mobile apps can benefit allergic rhinitis patients.

PMID- 30187769
TI  - Ixekizumab: A Review of Its Use for the Management of Moderate to Severe Plaque
      Psoriasis.
AB  - OBJECTIVE: To review the efficacy, safety, and place in therapy of ixekizumab for
      the treatment of moderate to severe plaque psoriasis. DATA SOURCES: PubMed (1966
      to July 2018) and clinicaltrials.gov were searched using the terms ixekizumab,
      LY2439821, interleukin-17, and psoriasis. STUDY SELECTION AND DATA EXTRACTION:
      Human studies published in peer-reviewed medical journals in English were used.
      DATA SYNTHESIS: The efficacy and safety of ixekizumab has been primarily reported
      by 4 phase III trials (UNCOVER-1, UNCOVER-2, UNCOVER-3, and UNCOVER-J) and
      multiple post hoc analyses. The average proportions of patients achieving a 75%,
      90%, and 100% reduction in their Psoriasis Area and Severity Index (PASI) were
      89%, 70%, and 38%, respectively, after 12 weeks of therapy. PASI75 was maintained
      for up to 3 years in 80.5% of participants. Ixekizumab was statistically
      significantly more effective than ustekinumab, with 76.5%, compared with 59%, of
      patients achieving PASI90 in 52 weeks. The most common adverse events include
      nasopharyngitis (14.1%), upper respiratory tract infections (7.9%), and injection
      site reactions (6.8%), which are similar to that for other biological agents. The
      risk of inflammatory bowel disease may be increased with ixekizumab. Relevance to
      Patient Care and Clinical Practice: This review summarizes and evaluates clinical
      data regarding the efficacy and safety of ixekizumab and discusses relevant
      differences compared with other biological agents used for the management of
      chronic plaque psoriasis. CONCLUSIONS: Ixekizumab is a highly efficacious and
      well-tolerated treatment option for patients with moderate to severe plaque
      psoriasis.

PMID- 30187771
TI  - Erratum: "A Novel Method for the Development of Environmental Public Health
      Indicators and Benchmark Dose Estimation Using a Health-Based Endpoint for
      Chlorpyrifos".

PMID- 30187770
TI  - Reactive Sulfur Species Emerge as Gliotransmitters to Support Memory via
      Sulfuration-Dependent Gating of NR2A-Containing N-Methyl-d-Aspartate Subtype
      Glutamate Receptor Function.
AB  - AIMS: Astrocytes have been revealed as a controller of synaptic plasticity and
      memory via releasing gliotransmitters. Our recent findings showed that reactive
      sulfur species (RSS), including hydrogen sulfide (H2S) and polysulfide (H2Sn),
      regulated the availability of d-serine, which is a well-known gliotransmitter
      that is involved in synaptic plasticity. An interesting question is whether RSS,
      which are small molecules, can function as direct gliotransmitters to integrate
      astrocyte-neuron interactions throughout the memory process. RESULTS: We found
      that hippocampal RSS level increased significantly in response to learning. We
      further demonstrated that the activity-triggered RSS signal controlled memory
      formation by using pharmacological and genetic approaches. The RSS-supporting
      memory was primarily conferred by enzymes that were mainly located in astrocytes,
      including cystathionine beta-synthase (CBS) and mercaptopyruvate
      sulfurtransferase (3-MST), and the memory-promoting effects were mostly dependent
      on sulfration of the NR2A subunit of N-methyl-d-aspartate subtype glutamate
      receptors (NMDARs). Further, RSS were demonstrated to buffer the strong
      inhibitory effect of synaptically released zinc on NR2A-containing NMDARs.
      Innovation and Conclusion: These results suggest that glial-derived RSS signals
      can serve as direct gliotransmitters that regulate memory formation through the
      redox modulation of postsynaptic receptors; this conclusion will enrich the
      gliotransmission hypothesis. Antioxid. Redox Signal. 00, 000-000.

PMID- 30187772
TI  - Environmental Chemicals in Breast Milk and Formula: Exposure and Risk Assessment
      Implications.
AB  - BACKGROUND: Human health risk assessment methods have advanced in recent years to
      more accurately estimate risks associated with exposure during childhood.
      However, predicting risks related to infant exposures to environmental chemicals
      in breast milk and formula remains challenging. OBJECTIVES: Our goal was to
      compile available information on infant exposures to environmental chemicals in
      breast milk and formula, describe methods to characterize infant exposure and
      potential for health risk in the context of a risk assessment, and identify
      research needed to improve risk analyses based on this type of exposure and
      health risk information. METHODS: We reviewed recent literature on levels of
      environmental chemicals in breast milk and formula, with a focus on data from the
      United States. We then selected three example publications that quantified infant
      exposure using breast milk or formula chemical concentrations and estimated
      breast milk or formula intake. The potential for health risk from these dietary
      exposures was then characterized by comparison with available health risk
      benchmarks. We identified areas of this approach in need of improvement to better
      characterize the potential for infant health risk from this critical exposure
      pathway. DISCUSSION: Measurements of chemicals in breast milk and formula are
      integral to the evaluation of risk from early life dietary exposures to
      environmental chemicals. Risk assessments may also be informed by research
      investigating the impact of chemical exposure on developmental processes known to
      be active, and subject to disruption, during infancy, and by analysis of exposure
      response data specific to the infant life stage. Critical data gaps exist in all
      of these areas. CONCLUSIONS: Better-designed studies are needed to characterize
      infant exposures to environmental chemicals in breast milk and infant formula as
      well as to improve risk assessments of chemicals found in both foods.
      https://doi.org/10.1289/EHP1953.

PMID- 30187773
TI  - REDOX-DRIVEN SIGNALING: 2-OXO ACID DEHYDROGENASE COMPLEXES AS SENSORS AND
      TRANSMITTERS OF METABOLIC IMBALANCE.
AB  - SIGNIFICANCE: The paper develops a holistic view on production of reactive oxygen
      species (ROS) by 2-oxo acid dehydrogenase complexes. Recent advances. Catalytic
      and structural properties of the complexes and their components evolved to
      minimize damaging effects of side reactions, including ROS generation,
      simultaneously exploiting the reactions for homeostatic signaling. CRITICAL
      ISSUES: Side reactions of the complexes, characterized in vitro, are analysed in
      view of protein interactions and conditions in vivo. Quantitative data support
      prevalence of the forward 2-oxo acid oxidation over the backward NADH oxidation
      in feeding physiologically significant ROS production by the complexes. Special
      focus on interactions between the active sites within 2-oxo acid dehydrogenase
      complexes highlights the central relevance of the complex-bound thiyl radicals in
      regulation of, and signaling by complex-generated ROS. The thiyl radicals arise
      when dihydrolipoyl residues of the complexes regenerate FADH2 from the flavin
      semiquinone co-produced with superoxide anion radical in 1e- oxidation of FADH2
      by molecular oxygen. FUTURE DIRECTIONS: Interaction of 2-oxo acid dehydrogenase
      complexes with thioredoxins, peroxiredoxins and glutaredoxins mediates scavenging
      of the thiyl radicals and ROS generated by the complexes, underlying signaling of
      disproportional availability of 2-oxo acids, CoA and NAD+ in key metabolic branch
      points through thiol-disulfide exchange and medically important HIF, mTOR, PARP
      and sirtuins. High reactivity of the co-produced ROS and thiyl radicals to iron
      sulfur clusters and nitric oxide, peroxynitrite reductase activity of
      peroxyredoxins and transnitrosylating function of thioredoxin, implicate the side
      reactions of 2-oxo acid dehydrogenase complexes in nitric-oxide-dependent
      signaling and damage.

PMID- 30187774
TI  - The Safe Recipient of SSC Transplantation Prepared by Heat Shock With Busulfan
      Treatment in Mice.
AB  - Safety is the chief consideration in recipient preparation of spermatogonial stem
      cell (SSC) transplantation in mammals, especially humans. In this study, we
      compared the safety of the SSC transplantation recipients that were prepared both
      by testes heat shock plus testes busulfan injection (heat shock+busulfan(t)) and
      by busulfan intraperitoneal injection (busulfan i.p.) only. Our results showed
      that heat shock+busulfan(t) treatment significantly ( p < 0.05) reduced mortality
      in mice and did not produce bone marrow cell toxicity. Furthermore, heat
      shock+busulfan(t) treatment directly damaged SSCs and exhausted almost all of the
      germ cells in the testis; the exhaustion of these cells is considered a key
      factor in the successful preparation of the recipients. Therefore, we used heat
      shock+busulfan(t) treatment to prepare recipients of SSC transplantation. Two
      months after SSC transplantation, the number and length of donor SSC-derived
      colonies in the testis of recipient in heat shock+busulfan(t) group was closed to
      that in busulfan i.p. group. Therefore, compared with busulfan i.p. treatment,
      heat shock+busulfan(t) treatment improved the safety of recipient preparation
      without reducing the efficiency of SSC transplantation. Two GFP-positive
      offspring were produced from 1 of the 20 recipients that had mated with female
      mice 72 days after SSC transplantation. In conclusion, heat shock with busulfan
      treatment is a safe method to prepare the recipient of SSC transplantation in
      mice.

PMID- 30187776
TI  - Bilateral Transorbital and Transnasal Endoscopic Resection of a Frontal Sinus
      Osteoblastoma and Orbital Mucocele: A Case Report and Review of the Literature.
AB  - OBJECTIVE: Describe a novel treatment approach to a rare bony neoplasm in the
      frontal sinus. STUDY DESIGN: Case report. METHODS: Retrospective chart review of
      an osteoblastoma of the frontal sinuses complicated by a right orbital mucocle.
      Demographic, endoscopic, radiographic, pathologic, and surgical data were
      collected for synthesis and review. MEDLINE, Embase, and Cochrane databases were
      searched from 1977 to 2017 to review publications of surgical management of
      frontal sinus neoplasms. RESULTS: A single female patient with a large frontal
      sinus osteoblastoma was successfully treated with a bilateral transorbital and
      transnasal approach. The right orbital mucocele was marsupialized into the
      frontal sinus. Gross total resection of the tumor was achieved, with complete
      resolution of the presurgical morbidity. The surgery was tolerated well without
      iatrogenic injury or sequela. CONCLUSION: Frontal sinus osteoblastoma is a rare
      condition. Complete surgical excision is considered curative. Various endoscopic
      and open approaches have been described. Here we show the feasibility and
      efficacy of a multiportal strategy in the successful management of a large
      frontal sinus osteoblastoma complicated by a right orbital mucocele.

PMID- 30187775
TI  - Micro-RNAS Regulate Metabolic Syndrome-induced Senescence in Porcine Adipose
      Tissue-derived Mesenchymal Stem Cells through the P16/MAPK Pathway.
AB  - Mesenchymal stem cells (MSCs) constitute an important repair system, but may be
      impaired by exposure to cardiovascular risk factors. Consequently, adipose tissue
      derived MSCs from pigs with the metabolic syndrome (MetS) show decreased
      vitality. A growing number of microRNAs (miRNAs) are recognized as key modulators
      of senescence, but their role in regulating senescence in MSC in MetS is unclear.
      We tested the hypothesis that MetS upregulates in MSC expression of miRNAs that
      can serve as post-transcriptional regulators of senescence-associated (SA) genes.
      MSCs were collected from swine abdominal adipose tissue after 16 weeks of Lean or
      Obese diet ( n = 6 each). Next-generation miRNA sequencing (miRNA-seq) was
      performed to identify miRNAs up-or down-regulated in MetS-MSCs compared with Lean
      MSCs. Functional pathways of SA genes targeted by miRNAs were analyzed using gene
      ontology. MSC senescence was evaluated by p16 and p21 immunoreactivity, H2AX
      protein expression, and SA-beta-Galactosidase activity. In addition, gene
      expression of p16, p21, MAPK3 (ERK1) and MAPK14, and MSC migration were studied
      after inhibition of SA-miR-27b. Senescence biomarkers were significantly elevated
      in MetS-MSCs. We found seven upregulated miRNAs, including miR-27b, and three
      downregulated miRNAs in MetS-MSCs, which regulate 35 SA genes, particularly MAPK
      signaling. Inhibition of miR-27b in cultured MSCs downregulated p16 and MARP3
      genes, and increased MSC migration. MetS modulates MSC expression of SA-miRNAs
      that may regulate their senescence, and the p16 pathway seems to play an
      important role in MetS-induced MSC senescence.

PMID- 30187777
TI  - Peripheral nerve injury, scarring, and recovery.
AB  - Peripheral nerve injuries (PNI) resulting from trauma can be severe and
      permanently debilitating. Despite the armamentarium of meticulous microsurgical
      repair techniques that includes direct repair, grafting of defects with autograft
      nerve, and grafting with cadaveric allografts, approximately one-third of all PNI
      demonstrate incomplete recovery with poor restoration of function. This may
      include total loss or incomplete recovery of motor and/or sensory function,
      chronic pain, muscle atrophy, and profound weakness, which can result in lifelong
      morbidity. Much of this impaired nerve healing can be attributed to perineural
      scarring and fibrosis at the site of injury and repair. To date, this challenging
      clinical problem has not been adequately addressed. In this review, we summarize
      the existing literature surrounding biological aspects of perineural fibrosis
      following PNI, detail current strategies to limit nerve scarring, present our own
      work developing reliable nerve injury models in animal studies, and discuss
      potential future studies which may ultimately lead to new therapeutic strategies.

PMID- 30187778
TI  - Response surface modeling of reductions in uropathogenic Escherichia coli
      biofilms on silicone by cranberry extract, caprylic acid, and thymol.
AB  - A response surface methodology was used to build a model to predict reductions in
      uropathogenic Escherichia coli biofilms in response to three compounds: cranberry
      extract [CB] at 3.0-9.0%, and caprylic acid [CAR] and thymol [TM] at 0.01%-0.05%.
      The predictive model for microbial reduction had a high regression coefficient
      (R2 = 0.9988), and the accuracy of the model was verified (R2 = 0.9527). Values
      of CAR, TM, and the quadratic term CAR2 were the most significant (P < 0.0001)
      for bacterial reduction. Interactions between CB and CAR, and TM and CB, also
      affected bacterial reduction. The optimum conditions (a 5.8 log10 reduction)
      determined by ridge analysis were 8.3% CB +0.04% CAR +0.04% TM at 37  degrees C
      for 1 min. The model could be used to predict the most cost-efficient amounts of
      antimicrobial agents for anti-urinary tract infection products such as catheter
      lock solution and antimicrobial coatings for catheters.

PMID- 30187779
TI  - Development of Methodology and Study Protocol: Safety and Efficacy of a Single
      Subretinal Injection of rAAV.hCNGA3 in Patients with CNGA3-Linked Achromatopsia
      Investigated in an Exploratory Dose-Escalation Trial.
AB  - Achromatopsia is an autosomal recessively inherited congenital defect
      characterized by a lack of cone photoreceptor function, leading to severely
      impaired vision. In this clinical study, achromatopsia patients were treated with
      a single subretinal injection of rAAV.hCNGA3 to restore cone function. The focus
      of this trial was on the safety of the treatment. After surgery, patients were
      monitored in eight extensive visits during the first year, followed by a 4-year
      follow-up period with annual visits. For essential complementation of the
      standard ophthalmological and systemic examinations, disease-specific methods
      were developed to assess the safety, efficacy, and patient-reported outcomes in
      this trial.

PMID- 30187780
TI  - In vitro antibacterial and cytotoxic activities of carvacrol and terpinen-4-ol
      against biofilm formation on titanium implant surfaces.
AB  - This study evaluated the antibacterial properties of carvacrol and terpinen-4-ol
      against Porphyromonas gingivalis and Fusobacterium nucleatum and its cytotoxic
      effects on fibroblast cells. The minimum inhibitory concentration (MIC) and the
      minimum bactericidal concentration (MBC) were examined. The minimum biofilm
      inhibition concentration (MBIC) was evaluated by XTT assay. Biofilm
      decontamination on titanium surfaces was quantified (CFU ml-1), evaluated by
      confocal laser scanning microscopy (CLSM) and cytotoxic activity by MTT. The MIC
      and MBC for carvacrol were 0.007% and 0.002% for P. gingivalis and F. nucleatum,
      and 0.06% for terpinen-4-ol for both microorganisms. The MBIC for carvacrol was
      0.03% and 0.06% for P. gingivalis and F. nucleatum, and for terpinen-4-ol was
      0.06% and 0.24%. The results indicated anti-biofilm activity using carvacrol
      (0.26%, 0.06%) and terpinen-4-ol (0.95%, 0.24%) and showed cytotoxic activity
      similar to chlorohexidine (CHX). However, terpinen-4-ol (0.24%) showed higher
      cell viability than other treatments. Carvacrol and terpinen-4-ol showed
      antibacterial activity in respect of reducing biofilms. Moreover, CHX-like
      cytotoxicity was observed.

PMID- 30187781
TI  - Spontaneous early first and second trimester uterine rupture following robotic
      assisted myomectomy.

PMID- 30187782
TI  - Comparative analysis of stimulation and binding characteristics of adenosine
      analogs to AMP-activated protein kinase.
AB  - To compare the stimulation and binding characteristics of adenosine analogs
      including AMP, IMM-H007, and M1, to AMPK, and to explore the potential mechanism
      underlying the regulation effect of adenosine analogs on AMPK activity, [gamma
      32P]ATP assay, circular dichroism experiments and molecular docking test were
      performed. We found that the interactions with Thr86, Thr88, and His150 in site 1
      are probably the reason why the affinities of IMM-H007, M1, and adenosine are
      comparable but their allosteric activation on AMPK varies greatly, partly
      interpreting the mechanism of AMPK activity regulated by adenosine analogs.

PMID- 30187783
TI  - Insights into the nature of female sexuality from the perspective of female
      stroke survivors.
AB  - AIM: The purpose of this study was to provide insights into the nature of female
      sexuality from the perspective of one group of women following a stroke. METHOD:
      Nine female stroke survivors from metropolitan and surrounding districts of
      Sydney, Australia participated in face to face semi-structured interviews about
      sexuality after stroke. The age of stroke survivors ranged from 31 to 70 years.
      The majority of females identified as heterosexual (n = 8). Length of time
      between stroke and interview ranged from 1 year, 2 months to 15 years, 9 months.
      The interviews were digitally recorded and transcribed. Braun and Clarke's 6
      steps of thematic analysis were used to answer the question: what is the nature
      of female sexuality? RESULTS: The women in this study saw themselves as sexual
      beings and communicated a tacit knowledge of the nature of female sexuality.
      Female sexuality was described as having two distinct, but related aspects, that
      captured "the being" and "the doing" of female sexuality. These encompassed a
      woman's way of being female and expressions of that way of being through
      engagement in specific activities. CONCLUSIONS: The findings of this study
      underline the importance of addressing sexuality as part of rehabilitation and
      provide some guidance about what might be important to address. Implications for
      Rehabilitation Sexuality should be addressed by clinicians as part of person
      centred rehabilitation. Understanding "the being" and "the doing" of female
      sexuality is a pre-requisite for understanding female sexuality post-stroke.
      Idealised constructions of being female formulated pre-stroke may continue to be
      points of reference for self-assessment post-stroke, hence need to be understood
      when seeking to support a positive sense of self. The influence of significant
      others on the self-esteem of females may be important to consider for some
      individuals post-stroke.

PMID- 30187784
TI  - A novel preoperative scoring system based on 18-FDG PET-CT for predicting lymph
      node metastases in patients with high-risk endometrial cancer.
AB  - The purpose of this study was to develop a model predicting the probability of
      pelvic-paraaortic node metastases in high-risk endometrial cancer patients. This
      trial included 41 high-risk endometrial cancer patients. All of the patients
      underwent an 18-FDG PET-CT followed by surgical staging, including a pelvic and
      paraaortic lymphadenectomy. We developed a useful scoring system combining
      weighted risk factors derived from a regression model: (3 * presence PET-CT
      involvement) + (3 * PET-CT maximum standardised uptake value >=20) + (2 *
      diabetes comorbidity) + (1 * age >=60 years) + (1 * body mass index >=30). The
      area under the curve of the resulting score was 0.848. There was 75% sensitivity,
      89% specificity and a 75% positive predictive value and 89% negative predictive
      value when a score of 6 was used as the cut-off. Our novel preoperative scoring
      system is an accurate method for the preoperative evaluation of lymph node
      metastases, and thus will aid gynaecological oncologists in selecting EC patients
      who may benefit from a lymphadenectomy. Impact statement What is already known on
      this subject? Endometrial cancer (EC) is a common gynaecological malignancy.
      Surgical staging is currently the standard treatment and the gold standard for
      evaluating lymph node metastases (LNm) is a surgical assessment (Chan et al. 2006
      ). Three previous randomised clinical studies failed to find a clear therapeutic
      role for the lymphadenectomy; thus, the utility of this surgical procedure in
      high-risk early-stage EC remains under debate (Benedetti Panici et al. 2008 ;
      Kitchener et al. 2009 ; Signorelli et al. 2015 ). Non-invasive techniques that
      accurately identify lymph node metastases would reduce costs and complications.
      What do the results of this study add? Our developed novel scoring system that is
      based on positron emission tomography-computer tomography (PET-CT) with 2-deoxy-2
      (18F) flouro-2-D-glucose (FDG) may facilitate the identification of patients at
      an increased risk of LNm. What are the implications of these finding for clinical
      practice and/or further research? This study shows that our novel preoperative
      scoring system provides an accurate method for the preoperative evaluation of
      LNm, and thus could guide gynaecologic oncologists in selecting the high-risk
      endometrial cancer patients who may benefit from a systematic lymphadenectomy.
      Further larger, prospective studies are needed to confirm the accuracy and the
      feasibility of our scoring system.

PMID- 30187785
TI  - Laparoscopic surgery for gastric cancer: where are we now and where are we going?
AB  - INTRODUCTION: Minimally-invasive surgery is gaining increasing popularity for the
      management of gastric cancer (GC). Areas covered: The authors hereby
      comprehensively and systematically reviewed the randomized and/or prospective
      evidence on laparoscopic gastrectomy (LG) for GC. For early GC located in the
      distal stomach, various randomized trials have demonstrated the superiority/non
      inferiority of LG especially in reducing surgical trauma and enhancing
      postoperative recovery without compromising surgical safety and oncologic
      efficacy. For advanced GC, while multicenter large-scale randomized evidence has
      demonstrated the safety and feasibility of LG by experienced hands, the long-term
      survival which is to be clarified by several ongoing trials are crucial to
      determine whether a more widespread application is acceptable. Randomized
      evidence regarding the application of laparoscopic total or proximal gastrectomy,
      which is technically challenging, is scarce. Various attempts in modification of
      the traditional laparoscopic approach to further reduce the trauma have been
      evaluated, such as single-incision and totally LG. LG is becoming increasingly
      individualized and precise. Expert commentary: The current randomized and/or
      prospective evidence supports the non-inferiority of laparoscopic surgery
      especially for the management of early GC located in the distal stomach, while
      the definitive efficacy of the laparoscopic approach for more surgically
      challenging situations remains largely explorative and investigative.

PMID- 30187786
TI  - Perineal trauma: incidence and its risk factors.
AB  - Perineal trauma can lead to short- and long-term complications for the mother.
      The purpose of this study was to determine the incidence of perineal trauma and
      its related factors. In this cross-sectional study, the maternal, neonatal,
      obstetric and childbirth information for all women who delivered in Kashan city
      hospitals was studied. Data were analysed using the Chi-square test, the t-test
      and logistic regression. The incidence of perineal trauma was 84.3%. Ninety-five
      percent of the primiparous women and 43.9% of the multiparous women had an
      episiotomy ([p value<.001], AOR = 24.4). The chance of birth trauma in the cases
      of younger maternal age, increasing gestational age, induction of labour, fundal
      pressure, Iranian nationality and nulliparity are increased. The incidence of
      perineal trauma in this study was high and should be minimised with a limited use
      of an episiotomy. It is recommended that midwives and obstetricians pay more
      attention to the women at risk. Impact Statement What is already known on this
      subject? Perineal trauma is common in vaginal delivery. Scientific literature
      shows several predictors of perineal trauma such as maternal age, parity,
      induction of labour, gestational age and birth weight, etc.; although in other
      studies some of these variables were not associated with perineal trauma.
      Considering that the findings about the factors associated with birth injuries
      are controversial, we decided to assess the incidence of perineal trauma and its
      risk factors during childbirth. What the results of this study add? This study
      indicated a high incidence of perineal trauma and agrees with the existing
      literature that maternal age, parity, the induction of labour, gestational age,
      fundal pressure and nationality are associated with perineal trauma; however,
      other factors were not found as predictors in our study. What the implications
      are of these findings for clinical practice and/or further research? Our results
      agreed with the existing literature regarding some predictors of perineal trauma
      but not for birth weight, foetal distress, second stage duration, hospital type,
      etc. This data could be used to implement protocols for reducing the rate of a
      routine episiotomy, considering too the high risk women for the prevention of
      perineal trauma.

PMID- 30187787
TI  - From staff nurse to nurse consultant: Continuing professional development part 5:
      Learning from experience.
AB  - John Fowler, Educational Consultant, explores CPD for the clinically based nurse,
      looking at demonstrating and validating experiential learning.

PMID- 30187789
TI  - Evaluation of a one-piece soft convex ostomy appliance: a prospective,
      multicentre, open-label pilot study.
AB  - Leakage of stomal effluent is considered by people living with a stoma to be the
      key factor that negatively impacts their quality of life (QoL). This non
      randomised pilot study evaluated the performance of a new stoma appliance,
      Flexima(r) Active O Convex in 40 ostomy patients with a flat, flush or slightly
      retracted stoma over a 14-day period. Leakage was reported for the wear time of
      each pouch by the patients. On 79% of occasions, the patient reported no leakage
      under the skin protector. The appliance was very well tolerated and the condition
      of the patients' peristomal skin was maintained throughout the study. The
      performance was rated as 'good' or 'very good' by most of the patients. The
      results of this study have shown that the design of this one-piece soft convex
      appliance can prevent leakage and protect peristomal skin by providing a safe
      seal around the stoma. It was also reported as being flexible and comfortable to
      wear.

PMID- 30187790
TI  - End of year report cards from NHS Resolution and the CQC.
AB  - John Tingle, Associate Professor (Teaching and Scholarship), Nottingham Trent
      University, discusses two reports looking at the beginning and end stages of
      patient safety failures.

PMID- 30187788
TI  - 3rd International Conference in Nursing (ICON), 20-21 May 2017, Indonesia.
AB  - The event was hosted in Malang, East Java, Indonesia, by the School of Nursing,
      Faculty of Medicine, Brawijaya University. Below is a selection of abstracts from
      among the 70 papers that were presented.

PMID- 30187791
TI  - Fitness to Practise proposals place the focus on patient safety and openness.
AB  - Sam Foster, Chief Nurse, Oxford University Hospitals, welcomes the
      recommendations emerging from the latest review and highlights the importance of
      investigating systemic, as well as human, factors.

PMID- 30187792
TI  - A history of stoma care in Southern Africa: from the pioneers to today.

PMID- 30187793
TI  - How nurse leadership has evolved.
AB  - Alan Nobbs, Senior Programme Lead, NHS Leadership Academy, concludes a series of
      blogs on his nursing career by exploring changes in leadership development and
      stresses that the nursing voice is as crucial as ever.

PMID- 30187794
TI  - Using the Plan, Do, Study, Act cycle to enhance a patient feedback system for
      older adults.
AB  - Patient feedback about healthcare experiences has gained increasing attention as
      an essential and meaningful source of information for identifying gaps and
      developing effective action plans for improving the quality of care. As
      experiences differ across patient groups, flexible and responsive feedback
      systems are essential. The population of older adults is growing rapidly; it
      constitutes an increasing proportion of the NHS client base. This group wants to
      have a say in their care and their views are critical in any performance
      assessment of a modern healthcare system. Nevertheless, collecting feedback data
      from older adults presents unique challenges, due to chronic conditions and
      comorbidities involving vision, hearing, speech and cognitive processing. In
      addition, nurses often find it difficult to act on feedback data in order to make
      quality improvements. This difficulty is associated with poor leadership, absence
      of explicit targets and an action plan, and the nature of clinical change
      required. This article offers insight into the development of a local innovation
      centred on enhancing the feedback system in a medical rehabilitation ward for
      older adults. A model for improvement in the form of the Plan, Do, Study, Act
      (PDSA) cycle provided a structured learning approach to facilitate the planning,
      testing, analysing and refining of the feedback system.

PMID- 30187795
TI  - Enhancing the experience of transition from child to adult health services.
AB  - Emeritus Professor Alan Glasper, from the University of Southampton, discusses
      transition and how various publications have attempted to enhance care delivery
      to this vulnerable group of patients.

PMID- 30187796
TI  - Enhancing the quality of life for stoma patients with appropriate accessory use.

PMID- 30187797
TI  - Adapting hospital wards to the needs of patients with dementia.

PMID- 30187798
TI  - Immunosuppression following organ transplantation. Part 1: mechanisms and
      immunosuppressive agents.
AB  - Solid organ transplantation has revolutionised medical care by providing a
      definitive cure for a wide spectrum of end-stage medical conditions. This
      treatment, however, does not come without complications and poses the risks of
      rejection, life-threatening infection, malignancies and recurrent organ failure,
      with significant impacts on patient outcomes. One of the major challenges
      involved in optimising post-transplant outcomes is managing the immune system's
      response to the transplanted graft and preventing organ rejection. This is mainly
      accomplished through the use of immunosuppressant agents, which have become a
      mainstay of treatment for a majority of post-transplant patients. This article,
      the first of two parts, discusses the concept of immunosuppression and its
      importance in the care of patients who have received an organ transplant. It
      focuses on the pathophysiologic mechanisms involved in transplant rejection and
      discusses the pharmacologic aspects of immunosuppression and its implications for
      patient care.

PMID- 30187799
TI  - Stoma Care Nurse of the Year: Runner up 2018.

PMID- 30187800
TI  - Do training and needle-safety devices prevent needlestick injuries? A
      systematised review of the literature.
AB  - This systematised review was undertaken to appraise research on the effects of
      training and the use of needle-safety devices (NSDs) on the prevention of
      needlestick injuries (NSIs) among health workers, focusing on a European
      perspective. A literature search from 2007 to 2017 was performed, which
      identified six studies that investigated the introduction of training and NSDs
      and their affect on NSIs. The six chosen studies identified that training, as
      well as the adoption of NSDs, has an impact on preventing NSIs. However, further
      information is required on the content and mode of delivery of training and on
      which types of NSDs are most effective at preventing injuries. This will help
      healthcare workers to understand and implement the most effective strategies to
      prevent injuries. This article provides a critique of the research approaches
      used in the six studies.

PMID- 30187801
TI  - Nursing never stands still.

PMID- 30187802
TI  - Research and expert opinion on siting a stoma: a review of the literature.
AB  - Marking the optimal position for a stoma on the patient's body before an
      operation is likely to result in fewer postoperative problems such as appliance
      leakage. A literature search was undertaken to examine and evaluate current
      practice internationally. Four recent articles describe the procedure; these
      articles were consensus documents or expert opinion, with limited robust research
      to support the statements made. Despite some variations in techniques, there was
      general agreement within the articles. Interestingly, when comparing recent and
      historical information on stoma siting, there were reassuringly few changes.
      Thus, in practice, although poorly researched, it is considered essential for
      people to have their stoma site marked as part of their preoperative preparation
      before elective stoma-forming surgery.

PMID- 30187803
TI  - The Carillion crisis: the impact.

PMID- 30187805
TI  - Supporting our armed forces.

PMID- 30187804
TI  - Interventional cardiology: from balloons to stents ... and back?
AB  - The treatment of coronary artery disease has seen rapid change following the
      invention of percutaneous coronary intervention (PCI). Since its introduction and
      widespread adoption for the treatment of coronary artery disease, efforts have
      been underway to minimise both the acute and long-term complications associated
      with the procedures, resulting in varying degrees of success over the years.
      These measures have taken many forms, from the adjunctive drug treatment regimen
      that patients receive before, during and after procedures to the actual
      mechanical intervention to the vessels themselves. The current gold standard in
      the interventional field is second-generation drug-eluting stents. However, with
      ongoing research into new technologies and trials underway in absorbable and non
      stent treatments, it may soon be possible to achieve the goal of leaving no long
      term physical implant behind in the artery. This could overcome issues with
      inflammation associated with permanent foreign body implants and prove less
      limiting for future treatment if needed.

PMID- 30187806
TI  - TCR alphabeta+/CD19+ cell depletion in haploidentical hematopoietic allogeneic
      stem cell transplantation: a review of current data.
AB  - Allogeneic hematopoietic stem cell transplantation is a curative option for
      patients with a variety of diseases. Transplantation from a related
      haploidentical donor is being increasingly utilized for patients who lack an
      available human leukocyte antigen matched related or unrelated donor. One of the
      strategies used for haploidentical transplants involves selective depletion of T
      cells expressing the alphabeta T cell receptor and CD19+ B cells prior to
      transplant. This allows for the removal of cells responsible for graft-versus
      host disease and post-transplant lymphoproliferative disorder but maintains
      hematopoietic progenitor and stem cells for engraftment (CD34+ cells), as well as
      cells to elicit graft-versus-tumor effect and provide anti-infective activity
      (such as gamma-delta T cells and natural killer cells). The aim of this review
      article is to present and discuss the data available to date from studies
      utilizing this method of transplantation.

PMID- 30187807
TI  - In vitro and in vivo assessment of vitamin A encapsulation in a liposome-protein
      delivery system.
AB  - Vitamin A (VA) is an essential nutrient needed in small amounts by humans and
      supports a wide range of biological actions. Retinol, the most common and most
      biologically active form of VA has also been found to inhibit peroxidation
      processes in membranes and it has been widely used as an ingredient with
      pharmaceutical and nutritional applications. VA is a lipophilic molecule,
      sensitive to air, oxidizing agents, ultraviolet light and low pH levels. For
      these reasons, it is necessary for VA to be protected against oxidation. Another
      disadvantage in the application of VA is its low solubility in aqueous media.
      Both issues (sensitivity and solubility) can be solved by employing encapsulation
      techniques. Liposomes can efficiently encapsulate lipid-soluble materials, such
      as VA. The encapsulated materials are protected from environmental and chemical
      changes. A new liposome/beta-lactoglobulin formulation has been developed as a
      stable delivery system for VA. The aim of this study was the encapsulation of VA
      into beta-lactoglobulin-liposome complexes, recently developed in our laboratory.
      The in vivo bioavailability characterization of VA was tested after
      administration in laboratory animals (mice). In this report, we demonstrate that
      VA could be efficiently entrapped and delivered in a phospholipid-sterol-protein
      membrane resembling system, a newly synthesized promising carrier. Based on this
      finding, the phospholipid-sterol-protein membrane resembling system may be one of
      the promising approaches to enhance VA absorption and to overcome the formulation
      difficulties associated with lipophilic means. The carrier system described here
      has huge potential in food fortification applications to treat VA deficiency.

PMID- 30187808
TI  - Sanguinarine suppresses growth and induces apoptosis in childhood acute
      lymphoblastic leukemia.
AB  - Sanguinarine (Sang), a plant-derived compound isolated from the roots of
      Sanguinaria canadensis was evaluated for its potential pro-apoptotic effects in
      precursor B acute lymphoblastic leukemia (Pre-ALL) cell lines. Treatment of 697,
      REH, RS4;11, and SupB15 cell lines with Sang exhibited significant inhibition of
      cell viability via induction of apoptotic cell death. Sang-mediated apoptosis was
      found to be associated with the increased expression of proapoptotic bax with
      concomitant decrease of Bcl-2 expression leading to depolarization of
      mitochondria membrane resulting in loss of mitochondrial membrane potential
      (MMP). The reduced MMP caused the leakage in mitochondrial membrane and release
      of cytochrome c into the cytosol. The cytochrome c then mediates the activation
      of caspase-cascade and subsequently PARP cleavage. Furthermore, pretreatment with
      z-VAD-FMK, a pan-caspase inhibitor, abrogated Sang-induced inhibition of cell
      viability, induction of apoptosis. Sang treatment also reduced the
      phosphorylation of AKT and suppressed the expression of a number of anti
      apoptotic genes such as cIAP1, cIAP2, and XIAP. Sang mediates its anti-cancer
      activity by generation of reactive oxygen species (ROS) due to depletion of
      glutathione level in leukemic cell lines. Pretreatment of these cells with N
      acetyl cysteine (NAC) prevented Sang-induced depletion of glutathione level and
      mitochondrial-caspase-induced apoptosis. Finally, Sang treatment of Pre-ALL cell
      suppressed colony formation ability of these cells suggesting Sang has an anti
      leukemic potential. Altogether, our data suggest that Sang is an efficient
      inducer of intrinsic apoptotic cell death via generation of ROS and exhibition of
      anti-leukemic effect in Pre-ALL cells raises the possibility to develop Sang as a
      therapeutic modality for the treatment and management of Pre-ALL.

PMID- 30187809
TI  - OncomiR or antioncomiR: Role of miRNAs in Acute Myeloid Leukemia.
AB  - Acute Myeloid Leukemia (AML) is a hematopoietic progenitor/stem cell disorder in
      which neoplastic myeloblasts are stopped at an immature stage of differentiation
      and lost the normal ability of proliferation and apoptosis. MicroRNAs (miRNAs)
      are small noncoding, single-stranded RNA molecules that can mediate the
      expression of target genes. While miRNAs mean to contribute the developments of
      normal functions, abnormal expression of miRNAs and regulations on their
      corresponding targets have often been found in the developments of AML and
      described in recent years. In leukemia, miRNAs may function as regulatory
      molecules, acting as oncogenes or tumor suppressors. Overexpression of miRNAs can
      down-regulate tumor suppressors or other genes involved in cell differentiation,
      thereby contributing to AML formation. Similarly, miRNAs can down-regulate
      different proteins with oncogenic activity as tumor suppressors. We herein review
      the current data on miRNAs, specifically their targets and their biological
      function based on apoptosis in the development of AML.

PMID- 30187810
TI  - A rare MYC/BCL3 double-translocation and protein-expression in a diffuse large B
      cell lymphoma.

PMID- 30187811
TI  - Bendamustine alone or with rituximab modifies expression of apoptosis-regulating
      genes and proteins of CLL cells, depending on IGVH mutational status.
AB  - We studied whether bendamustine (BENDA) alone or with rituximab (RIT) modifies in
      vitro expression of apoptosis-involved genes and proteins of chronic lymphocytic
      leukemia (CLL) cells depending on IGVH mutational status. Circulating lymphocytes
      from 34 untreated patients (18 IGVH-MUT and 16 IGVH-UNMUT) were incubated with
      above drugs to evaluate proteins expression. Microarray analysis of 93 genes was
      performed in 14 patients. BENDA and BENDA + RIT increased expression of BAX and
      BBC3 in IGVH-MUT and IGVH-UNMUT groups, and significant differences in expression
      of above genes after BENDA + RIT were observed between both groups. Additionally,
      BENDA + RIT decreased NFkappaB and BCL-2 genes in IGVH-UNMUT patients and
      increased expression of P53, BAX and PUMA proteins in IGVH-MUT and UNMUT
      subjects. However, no significant differences were found between these groups. In
      conclusion, BENDA + RIT modified gene expression profile in CLL cells and
      affected expression of some apoptosis-regulating proteins in vitro. Expression of
      BAX and BBC3 depends on action of drugs and IGVH mutational status.

PMID- 30187812
TI  - Is fluorescence in-situ hybridization sufficient in patients with myelodysplastic
      syndromes and insufficient cytogenetic testing?
AB  - Chromosome banding analysis (CBA) in myelodysplastic syndromes (MDS) remains the
      'gold standard' for identification of chromosomal abnormalities, while interphase
      fluorescence in-situ hybridization (I-FISH) is mainly used to complement CBA.
      This study, retrospectively, evaluated CBA and I-FISH results in 600 patients
      with suspected MDS and determined the effect of CBA/FISH reallocation on IPSS-R.
      Our result demonstrated that in 7/586 (1.2%) patients with satisfactory
      karyotype, I-FISH provided additional information. In 25/453 (5.5%) of the
      patients with normal I-FISH, CBA detected chromosomal abnormalities, and in
      68/147 (46%) of the patients with abnormal I-FISH, CBA detected additional
      chromosomal aberrations. When 5q- aberration was alone or accompanied by
      additional abnormalities by I-FISH, CBA revealed a complex karyotype (16/25;64%,
      35/43;81%, respectively). Our results suggest that in cases of karyotype failure,
      if I-FISH is used alone, patients are at risk of being misclassified into the
      wrong cytogenetic risk groups and a repeat sample for CBA should be attempted.

PMID- 30187813
TI  - Signaling by discoidin domain receptor 1 in cancer metastasis.
AB  - Collagen is the most abundant component of tumor extracellular matrix (ECM). ECM
      collagens are known to directly interact with the tumor cells via cell surface
      receptor and play crucial role in tumor cell survival and promote tumor
      progression. Collagen receptor DDR1 is a member of receptor tyrosine kinase (RTK)
      family with a unique motif in the extracellular domain resembling Dictyostelium
      discoideum protein discoidin-I. DDR1 displays delayed and sustained activation
      upon interaction with collagen and recent findings have demonstrated that DDR1
      collagen signaling play important role in cancer progression. In this review, we
      discuss the current knowledge on the role of DDR1 in cancer metastasis and
      possibility of a potential therapeutic approach of DDR1 targeted therapy in
      cancer.

PMID- 30187815
TI  - Letter to Editor.

PMID- 30187814
TI  - Trends in Clinical Characteristics and Short-Term Outcome of HIV-Infected
      Patients at a Tertiary Care Hospital in South India.
AB  - BACKGROUND: Limited information is available on changing trends in HIV positive
      patients treated with first-line antiretroviral therapy from India. METHODS: The
      clinical characteristics and short-term outcome were compared between a
      retrospective group enrolled between January 2006 and March 2007 (06-07 group-100
      patients) and a prospective group enrolled between February 2011 and March 2012
      (10-12 group-85 patients). RESULTS: Median age was 36 and 38 years in 06-07 and
      10-12 groups, respectively. Median baseline CD4 count was 146 cells/mL3 in the 10
      12 group, and it was not significantly different from that of 06-07 group.
      Tuberculosis was diagnosed 3 times more commonly in the 10-12 group. The
      retention proportion at the end of 10 months was 68% in the 10-12 group when
      compared to that of 59% in the 06-07 group. CONCLUSION: There was a trend toward
      improved outcome over the period of time, but the attrition rate remained high.

PMID- 30187816
TI  - Attention to faces and gaze-following in social anxiety: preliminary evidence
      from a naturalistic eye-tracking investigation.
AB  - Social attentional biases are a core component of social anxiety disorder, but
      research has not yet determined their direction due to methodological
      limitations. Here we present preliminary findings from a novel, dynamic eye
      tracking paradigm allowing spatial-temporal measurement of attention and gaze
      following, a mechanism previously unexplored in social anxiety. 105 participants
      took part, with those high (N = 27) and low (N = 25) in social anxiety traits
      (HSA and LSA respectively) entered into the analyses. Participants watched a
      video of an emotionally-neutral social scene, where two actors periodically
      shifted their gaze towards the periphery. HSA participants looked more at the
      actors' faces during the initial 2s than the LSA group but there were no group
      differences in proportion of first fixations to the face or latency to first
      fixate the face, although HSA individuals' first fixations to the face were
      shorter. No further differences in eye movements were found, nor in gaze
      following behaviour, although these null effects could potentially result from
      the relatively small sample. Findings suggest attention is biased towards faces
      in HSA individuals during initial scene inspection, but that overt gaze-following
      may be impervious to individual differences in social anxiety. Future research
      should seek to replicate these effects.

PMID- 30187817
TI  - Identification of a novel GORASP2-ALK fusion in an ALK-positive large B-cell
      lymphoma.

PMID- 30187818
TI  - Maternal health services for refugee populations: Exploration of best practices.
AB  - The full scope of women's health needs is not necessarily addressed in refugee
      camps and after resettlement, particularly pregnancy and postnatal services. The
      aims of this research are to examine the maternal care services provided to
      refugee women in camps and after resettlement to the United States, and to
      analyse organisational successes and challenges in service provision. With this
      understanding, policies can improve service delivery for refugee women. We
      interviewed respondents from five organisations, ranging from local non-profits
      to international non-governmental organisations. Most of the organisations do not
      provide direct medical care, but rather education and social service support to
      clients, and in some cases midwife training. Their success stemmed from a focus
      on client capacity building, individualised support, effective partnerships, and
      cultural competency. Respondents described the need for physical resources,
      effective leadership, and additional personnel, especially with linguistic
      capabilities. The dialogue in the interviews supports themes of education as
      empowerment and client self-sufficiency. Respondents emphasised the importance of
      funding and policies that support their work. This knowledge can lead to improved
      models of service delivery and inform the development of best practices and
      policies in maternal and reproductive health for refugee women.

PMID- 30187820
TI  - Depressive Symptoms Are Associated With More Negative Functional Outcomes Than
      Anxiety Symptoms in Persons With Multiple Sclerosis.
AB  - Depression and anxiety are common among persons with multiple sclerosis (MS), and
      both negatively affect functional status. However, studies rarely account for
      overlap in depressive and anxiety symptoms on functional outcomes among people
      with MS. The authors aimed to examine the differential impact of depression and
      anxiety, measured by the Anxiety and Depression subscales of the Hospital Anxiety
      and Depression Scale (HADS-A and HADS-D), on functional outcomes among people
      with MS. Using a retrospective chart review of 128 people with MS, the authors
      used exploratory structural equation modeling to examine the relation of HADS-A
      and HADS-D to functional outcomes, namely employment status, fatigue (with the
      Fatigue Severity Scale), disability (with the Expanded Disability Status Scale
      [EDSS]), and cognition (with the Symbol Digit Modalities Test [SDMT]). After the
      authors controlled for the effects of covariates, HADS-A was negatively
      associated with EDSS (beta=-0.22, p<0.05) and positively associated with vocation
      (beta=0.23, p<0.05). In contrast, HADS-D was positively correlated with fatigue
      (beta=0.37, p<0.05) and EDSS (beta=0.26, p<0.05) and negatively correlated with
      vocation (beta=-0.32, p<0.05) and SDMT (beta=-0.28, p<0.05). HADS-A and HADS-D
      explained 5% of the variability in employment, 14.5% in fatigue, 1.6% in EDSS,
      and 4.3% in SDMT, beyond the effects of the covariates. Depressive symptoms have
      a significant negative impact on functional outcomes among people with MS,
      relative to anxiety symptoms. These findings support the importance of
      identifying and treating depressive symptoms among people with MS.

PMID- 30187819
TI  - Risk Factors for Complications following Introduction of Radical Surgery for
      Colon Cancer: A Consecutive Patient Series.
AB  - BACKGROUND: Rectal cancer surgery is standardized, resulting in improved
      survival. Colon cancer has fallen behind and therefore more radical surgical
      techniques have been introduced. One technique is complete mesocolic excision.
      The aim of this article was to study the complications after the introduction of
      standardized complete mesocolic excision in a single center. METHODS: Complete
      mesocolic excision was introduced in 2007, and data were collected from 286
      patients prior to surgery (2007-2010). The surgeon decided on open or
      laparoscopic surgery. Follow-up information was recorded until 31 December 2015.
      Complications were classified according to a modified Clavien-Dindo
      classification. RESULTS: Complications occurred in 47%, severe complications
      (grade III and IV) in 15%. In-hospital mortality was 3.5%. A total of 142
      patients (49.7%) were operated by open surgery. Logistic regression revealed
      anemia (p = 0.001), open surgery (p < 0.001), and long operating time (p < 0.001)
      as significant factors for complications in general. Multinomial logistic
      regression revealed that severe complications occurred more often in males (odds
      ratio: 2.56; 95% confidence interval: 0.98-6.68), patients with anemia (odds
      ratio: 3.49; 95% confidence interval: 1.27-9.60), elevated body mass index (odds
      ratio: 1.14; 95% confidence interval: 1.02-1.28), and in open surgery (odds
      ratio: 9.95; 95% confidence interval: 2.58-38.35). Age was not associated with
      severe complications. Survival was not significantly influenced by complications.
      Overall survival (5 years) was 90% among patients with complications and 92%
      among those without complications. CONCLUSION: Severe complications following the
      introduction of complete mesocolic excision are patient dependent and related to
      open surgery. Patients selected for laparoscopy had less number of complications;
      therefore, introducing complete mesocolic excision by laparoscopy is justified.
      Identification of these factors can improve selection of appropriate surgical
      approach and postoperative patient safety.

PMID- 30187821
TI  - Anxiety Independently Contributes to Severity of Freezing of Gait in People With
      Parkinson's Disease.
AB  - Freezing of gait is a disabling feature of Parkinson's disease, and it has been
      shown that nonmotor symptoms, such as anxiety and cognitive impairment, may be
      involved in the pathophysiology of the phenomenon. However, the association
      between freezing of gait severity and nonmotor symptoms is yet to be determined.
      Therefore, the overall aim of this study was to determine factors that contribute
      to severity of freezing of gait in people with Parkinson's disease. Participants
      (N=78) were assessed by disease-specific and self-report measures, including the
      Hospital Anxiety and Depression Scale (HADS), the Montreal Cognitive Assessment,
      and the Freezing of Gait Questionnaire (FOG-Q). Participants were classified as
      "freezers" if they scored >=1 on item 3 of the FOG-Q; the sum of items 3-6 was
      used to determine freezing of gait severity. Freezers (N=27) showed higher scores
      on the HADS anxiety (p=0.002) and HADS depression (p=0.006) subscales. A
      multivariate linear model showed that disease severity (as measured by using the
      modified Hoehn and Yahr scale) accounted for 31% of the variance in FOG-Q
      severity scores (p<0.001). The presence of HADS anxiety >=8 points increased the
      explained variance to 38% (p=0.010), and the full model (reached by adding the
      levodopa equivalent dose) explained 42% of the variance in freezing of gait
      severity (p=0.026). The findings provide additional support for the contribution
      of anxiety to greater freezing of gait severity, taking into account not only the
      frequency but the duration of the episodes, and suggest that anxiety should be
      routinely evaluated in people with Parkinson's disease who present with freezing
      of gait.

PMID- 30187822
TI  - The Relationship Between Prior Concussions and Depression Is Modified by Somatic
      Symptomatology in Retired NFL Athletes.
AB  - A positive relationship between sport-related concussion (SRC) history and
      depressive symptoms in retired National Football League (NFL) athletes has been
      observed, with self-rated physical functioning identified as a confounding
      factor. The authors examined the influence of somatic symptom endorsement on the
      relationship between SRC history and self-reported depressive symptom severity in
      retired NFL athletes. Forty-three former NFL athletes completed self-report
      inventories of depression (with the Beck Depression Inventory II) and somatic
      symptoms (with the adjusted Patient Health Questionnaire-15). A moderation
      analysis examined the influence of somatic symptoms on the relationship between
      SRC history and depressive symptom severity. SRC history and somatic symptoms
      accounted for a significant amount of depressive symptomology. SRC history was
      not significantly associated with depressive symptom severity at low levels of
      somatic symptoms but was significant at the mean and high levels. The effect of
      somatic symptoms on depressive symptoms was nearly twice that of SRC history. The
      relationship between SRC and depression is complex, and treatment of depression
      in retired athletes should address comorbid somatic symptoms.

PMID- 30187823
TI  - Weight Loss and Resolution of Comorbidities After Sleeve Gastrectomy: A Review of
      Long-Term Results.
AB  - BACKGROUND AND AIMS: Laparoscopic sleeve gastrectomy (SG) has massively increased
      in numbers over the last decade and is the most frequently performed bariatric
      procedure worldwide today. The aim of this review is to evaluate SG in terms of
      weight loss and resolution of comorbidities, based on data gained from the latest
      long-term studies available. MATERIAL AND METHODS: This review includes the
      results of any long-term studies on SG available at this point as well as a
      selection of short- and mid-term studies. RESULTS: There are only a handful of
      studies on sleeve gastrectomy with long-term follow-up available at this point.
      Conversion rates in these long-term studies amount to up to one-third of their
      cohorts; however, excess weight loss in patients maintaining their sleeve is over
      50%. Results on the resolution of comorbidities vary among the studies available
      today. SUMMARY: Sleeve gastrectomy is a valid bariatric method but one has to be
      aware of its limitations.

PMID- 30187824
TI  - High levels of healthcare utilization prior to diagnosis in idiopathic pulmonary
      arterial hypertension support the feasibility of an early diagnosis algorithm:
      the SPHInX project.
AB  - Idiopathic pulmonary arterial hypertension (iPAH) is a rare progressive, life
      shortening disease, usually diagnosed at an advanced stage. We hypothesize that
      patients with iPAH exhibit patterns of health-seeking behavior before diagnosis
      that will allow the development of earlier identification tools. The Sheffield
      Pulmonary Hypertension IndeX (SPHInX) project aims to develop a predictive
      algorithm based on routinely collected healthcare resource utilization (HCRU)
      data. This report focuses on the initial feasibility of the project, examining
      whether Hospital Episode Statistics (HES) data from the National Health Service
      in England have sufficient richness to support the development of an early
      diagnosis algorithm. This is a two-stage study. First, hospital interactions
      during 2009-2014 captured in HES data identified 127,815 adult patients with
      pulmonary hypertension (PH) ICD-10 codes, containing a probable iPAH cohort with
      incidence and demographics similar to the reported literature. HCRU was high in
      the three years before diagnosis. Second, to examine HCRU in patients with a
      confirmed iPAH diagnosis, we built the SPHInX dataset incorporating all patients
      investigated for suspected PH in the Sheffield Pulmonary Vascular Disease Unit
      during 2008-2016 (n = 6674). For the SPHInX dataset, data could be linked to HES
      in 98.6% of cases and patients with confirmed iPAH had similar levels of pre
      diagnosis HCRU. In conclusion, patients with probable iPAH identified using HES
      and patients with confirmed iPAH have high levels of HCRU for several years
      before diagnosis. Artificial intelligence models will now be used to develop the
      SPHInX algorithm to screen for undiagnosed iPAH in the general population.

PMID- 30187825
TI  - Wound Closure after Thyroid and Parathyroid Surgery: A Meta-Analysis of
      Randomized Controlled Trials.
AB  - AIMS: Wound closure after thyroidectomy and parathyroidectomy is associated with
      patients' satisfaction, perception of cosmetic appearance, and experience of
      postoperative pain. Subcutaneous sutures, clips, and tissue adhesive are the
      three major methods of wound closure. In this study, we conducted a meta-analysis
      of randomized controlled trials to evaluate the outcomes of these methods.
      METHODS: Relevant studies published before December 2017 were identified from
      PubMed, Embase, Cochrane Library, Scopus, and the ClinicalTrials.gov registry.
      Individual effect sizes were standardized, and a meta-analysis was conducted to
      calculate the pooled effect size by using random-effect models. The primary
      outcome was the cosmetic appearance, which was evaluated 4 weeks, 6 weeks, and 6
      months after surgery. The secondary outcomes were patient satisfaction,
      postoperative pain, and complications. RESULTS: A total of nine trials with 612
      patients were reviewed. No significant difference was observed in patient
      satisfaction, postoperative pain, and complications among the wound closure
      methods. However, according to surgeon assessment, the subcutaneous suture method
      resulted in a significantly more favorable cosmetic appearance than the clip
      method (mean difference: -1.47, 95% confidence interval: -2.72 to -0.23).
      CONCLUSION: In the current study, no differences were found in patient
      satisfaction and postoperative pain among the subcutaneous suture, clip, and
      tissue adhesive wound closure methods. However, surgeons provided a more
      favorable appraisal for the subcutaneous suture method because of the improved
      cosmetic appearance. The choice of the closure method should be based on
      surgeon's preference and cost.

PMID- 30187826
TI  - Functional Outcome After Lower Extremity Soft Tissue Sarcoma Treatment: A Pilot
      Study Based on Translated and Culturally Adapted Measures.
AB  - BACKGROUND AND AIMS: The present standard of care in treating lower extremity
      soft tissue sarcomas is function-sparing, limb-preserving resection and
      reconstruction with or without oncological therapy. The aim of this pilot study
      was to test the suitability and adequacy of the Finnish translations of two
      functional outcome questionnaires (Toronto Extremity Salvage Score and
      Musculoskeletal Tumor Society score) and to perform a preliminary investigation
      of functional outcomes of Finnish lower-limb soft tissue sarcoma patients after
      operative treatment. MATERIALS AND METHODS: Between June 2015 and December 2015,
      consecutive surgically treated outpatients were asked to participate in the
      study. Demographic, clinical, surgical, and oncological outcome data were
      collected. Two functional outcome questionnaires were used (Toronto Extremity
      Salvage Score and Musculoskeletal Tumor Society scores). A comparative analysis
      is presented. RESULTS: A total of 19 lower-limb soft tissue sarcoma patients with
      a mean follow-up time of 2 years and 10 months were included. All (n = 19)
      invited patients participated in the study. Mean age was 62.3 years. In total, 13
      had high-grade sarcomas. Eight wounds were closed directly, four used skin
      grafts, and five required flap reconstructions. One patient required a tumor
      prosthesis, and one required a rotationplasty. A total of 14 patients received
      oncological therapy. No problems or difficulties were reported in using and
      completing the Finnish versions of the Toronto Extremity Salvage Score or
      Musculoskeletal Tumor Society questionnaires. The overall Toronto Extremity
      Salvage Score and Musculoskeletal Tumor Society scores were 88 and 76,
      respectively. CONCLUSION: This pilot study suggests that the Finnish versions of
      the Toronto Extremity Salvage Score and Musculoskeletal Tumor Society
      questionnaires are suitable for measuring functional outcome after lower
      extremity soft tissue sarcomas treatment. Functional outcomes vary from moderate
      to excellent.

PMID- 30187828
TI  - Access to essential medicines in 195 countries: A human rights approach to
      sustainable development.
AB  - In 2008 the UN Special Rapporteur on the Right to Health published 72 right to
      health indicators in 194 health systems. We present a follow-up report of eight
      indicators for access to medicines to serve as a reference point for progress
      towards SDG Target 3.8 on essential medicines. Data for these eight indicators in
      2015 were collected and compared with the 2008 report. Between 2008 and 2015 we
      observed increased numbers of constitutions recognising access to medicines (7-13
      countries), countries with a national medicine policy (118-122) and with a
      national list of essential medicines (78-107). Public spending on pharmaceuticals
      decreased or rose modestly in most of the 44 countries. Median availability of a
      basket of lowest-priced generics increased in the public (63%-70% n = 9
      countries) and private (84%-92% n = 10) sectors. Median child immunisation rates
      remained constant for measles (around 90%) and improved for three doses of
      diphtheria-tetanus-pertussis (79%-86%). These eight indicators are useful and
      feasible, but should be further strengthened and expanded. Future monitoring
      exercises should use these indicators to screen progress and guide national
      governments' action to ensure universal access to essential medicines as part of
      the right to health.

PMID- 30187827
TI  - Antioxidant Preconditioning Improves the Paracrine Responsiveness of Bone Marrow
      Mesenchymal Stem Cells to Diabetic Wound Fluid.
AB  - Mesenchymal stem cells (MSCs) are a promising therapeutic tool for the treatment
      of nonhealing diabetic wounds. The pathological nature of the niche
      microenvironment limits the use of autologous cell therapy in diabetic patients.
      Prolonged exposure of endogenous MSCs to a pathological microenvironment in vivo
      reduces their ability to respond to environmental cues. This study investigated
      the effectiveness of ex vivo antioxidant treatment [N-acetylcysteine (7.5 mM NAC)
      and Ascorbic acid 2-phosphate (0.6 mM AAP)] to restore the paracrine function of
      diabetic MSCs. Healthy control [bone marrow stem cells derived from wild-type
      mice (SCWT)] (source: wild-type C57BL/6J mice) (n = 12) and
      impaired/dysfunctional [bone marrow stem cells derived from ob/ob mice (SCob)]
      (source: obese diabetic, B6.Cg-Lepob/J mice) (n = 12) MSCs were isolated. Ex vivo
      treatment groups (SCWT vs. SCob) were as follows: (1) no treatment (baseline
      phenotype), (2) stimulated with diabetic wound fluid (DWF) (baseline response),
      (3) antioxidant preconditioning (preconditioned phenotype), and (4) antioxidant
      preconditioned with subsequent stimulation with DWF (preconditioned response).
      The paracrine responsiveness on both the molecular (mRNA expression of 80
      cytokines and receptors, quantitative polymerase chain reaction microarray) and
      protein (23-plex bead-array Luminex assay) level was assessed. At baseline, 31
      genes were overexpressed (> * 2-fold) and 39 genes were underexpressed (> * 2
      fold) in SCob versus SCWT. In conditioned media, significant differences (P <
      0.05) were detected at baseline for two proinflammatory cytokines [tumor necrosis
      factor alpha (TNFalpha) and interferon gamma (IFNgamma)], four chemokines
      [keratinocyte chemoattractant (KC), granulocyte colony-stimulating factor (GCSF),
      Eotaxin, and macrophage chemoattractant protein (MCP1)], and one anti
      inflammatory cytokine [interleukin 10 (IL10)]. Following stimulation with DWF,
      significant differences (P < 0.05) were detected in the secretion of two
      chemokines [granulocyte macrophage colony-stimulating factor (GMCSF) and
      Eotaxin], three proinflammatory cytokines (TNFalpha, IFNgamma, and IL9), and four
      anti-inflammatory cytokines (IL10, IL4, IL13, and IL3). Antioxidant
      preconditioning significantly dampened the excessive TNFalpha response observed
      in SCob and improved the secretion of IL10. Taken together these data suggest
      that the combined ex vivo treatment of autologous stem cells with NAC and AAP
      could potentially be an effective strategy to restore the paracrine function of
      impaired diabetic MSCs before transplantation.

PMID- 30187829
TI  - Size-dependent Cortical Compaction Induces Metabolic Adaptation in Mesenchymal
      Stem Cell Aggregates.
AB  - Spontaneous assembly of human mesenchymal stem cells (hMSCs) into 3D aggregates
      enhances stem cell properties and enables formation of heterotypic organoids,
      which has significant implication in cell therapy and tissue engineering. While
      metabolic reprograming towards glycolysis is a salient feature of multicellular
      aggregates and it has commonly been attributed to oxygen diffusion limitations;
      however, recent studies have instead observed a limited decline in oxygen
      tension, in hMSC aggregates, challenging this view. Although aggregation of a
      dispersed cell population involves both changes in the physical and molecular
      environment most studies to date have focused on molecular gradients with limited
      investigation in biomechanical stress on the fate of aggregated cells. The
      objective of this study is to investigate how the mechanical gradient arising
      from aggregation induced cortical compaction alters the metabolic profile of
      human adipose derived mesenchymal stem cells (hASCs) by testing the hypothesis
      that size-dependent compaction in aggregates leads to differential cortical
      stress which induces metabolic reprogramming. Herein, we show that aggregation of
      multiple sizes covering a wide range of interest does not lead to hypoxic core
      formation but instead varying levels of cortical compaction, indicated by the
      balance between stress fiber formation and the deposition of extracellular matrix
      proteins, resulting in corresponding levels of metabolic reconfiguration.
      Increased glycolytic metabolism, increased mitochondrial fission, and increased
      release of aldolase A were all observed as a result of cortical compaction.
      Chemical inhibition with Gleevec, Wortmannin, and Y27632 almost completely
      abolishes the cortical stress induced enhancement in glycolytic properties. Our
      findings demonstrate that aggregation-induced biomechanical stress plays a
      central role in driving metabolic reprogramming.

PMID- 30187830
TI  - Noninvasive Localized Cold Therapy: A New Mode of Bone Repair Enhancement.
AB  - IMPACT STATEMENT: A variety of biological, mechanical, and physical therapeutic
      modalities of varying complexity, efficacy, cost, and safety profile have been
      developed to enhance bone healing. There have been sporadic reports of
      spontaneous bone formation after repeated cold exposure. In this study we report
      for the first time, the anabolic effect of cold exposure on bone healing in vivo
      resulting in a doubling of bone volume. Although the precise mechanism is not
      fully understood, cold is well known to stimulate osteoclastogenesis and modulate
      inflammation. The impact of this finding is considerable for tissue regeneration
      because cold application is noninvasive, safe, and easily implemented.

PMID- 30187831
TI  - The difficulty of studying race-ethnic stroke rehabilitation disparities in a
      community.
AB  - OBJECTIVE: Minority populations have worse stroke outcomes compared with non
      Hispanic whites (NHWs). One possible explanation for this disparity is
      differential allocation of stroke rehabilitation. We utilized a population-based
      stroke study to determine the feasibility of studying Mexican American-NHW
      differences in stroke rehabilitation in a population-based design including
      identification of community partners, development of standardized data collection
      instruments, and collection of pilot data. METHODS: As part of the Brain Attack
      Surveillance in Corpus Christi project, we followed 48 patients for the first 90
      days after stroke, and attempted to work with community partners to garner
      information on rehabilitation modalities used. With input from local occupational
      and physical therapists and speech language pathologists, we created data
      collection forms to capture rehabilitation activities and time spent on these
      activities and conducted a 3-month data collection pilot. RESULTS: Of the 79
      rehabilitation venues in the community, 63 (80%) agreed to participate. During
      the pilot, 545 data forms from 20 stroke patients were collected corresponding to
      ~18% of stroke patients. Forms were used by 13 partners during the pilot
      including 3 of 4 inpatient rehabilitation facilities, 4 of 13 skilled nursing
      facilities, 4 of 26 home health agencies, and 2 of 36 outpatient rehabilitation
      providers. CONCLUSIONS: Initial agreement from rehabilitation providers to
      participate in research was excellent, but completion of study related data
      collection forms was sub-optimal suggesting this approach is not feasible for a
      future population-based stroke rehabilitation study. Further methods to study
      post-stroke rehabilitation disparities in communities are needed.

PMID- 30187832
TI  - Malnutrition during late pregnancy exacerbates high-fat-diet-induced metabolic
      dysfunction associated with lower sympathetic nerve tonus in adult rat offspring.
AB  - OBJECTIVES: We aimed to assess the effects of a maternal protein-caloric
      restriction diet during late pregnancy on the metabolism of rat offspring fed a
      high-fat diet (HFD) during adulthood. METHODS: During late pregnancy, rat dams
      received either a low-protein (4%; LP group) or normoprotein (23%; NP group)
      diet. After weaning, the offspring were fed a standard diet (Control; C). Male
      offspring (60 days old) from both groups were then fed either the C diet or HFD
      until they were 90 days old. The adult offspring and maternal metabolic
      parameters and autonomic nervous system (ANS) were then evaluated. RESULTS: Dams
      exhibited low body weight gain and food intake during the LP diet consumption. At
      lactation, these dams showed high body weight gain, hypoinsulinemia and
      hyperglycemia. The maternal LP diet resulted in low body weights for the pups.
      There were also no differences in the metabolic parameters between the adult LP
      offspring that were fed the C diet and the NP group. Adults of both groups that
      were fed the HFD developed obesity associated with altered insulin/ glucose
      homeostasis and altered ANS activity; however, the magnitudes of these parameters
      were higher in the LP group than in the NP group. CONCLUSIONS: Maternal protein
      malnutrition during the last third of pregnancy malprograms the metabolism of rat
      offspring, resulting in increased vulnerability to HFD-induced obesity, and the
      correlated metabolic impairment might be associated with lower sympathetic nerve
      activity in adulthood.

PMID- 30187833
TI  - May-Thurner syndrome.

PMID- 30187836
TI  - Novel Nanoparticles for Tumor Targeting Drug Delivery.

PMID- 30187834
TI  - 29th SVM Scientific Sessions Highlights.

PMID- 30187837
TI  - Protein and Peptide Studies in Kidney Disease: Prediction, Diagnosis and
      Treatment.

PMID- 30187839
TI  - Senior Centres in Canada and the United States: A Scoping Review.
AB  - ABSTRACTSenior centres have been identified as a "focal point" for delivering
      services to the rapidly growing older adult populations in Canada and the United
      States. Despite this important role, academic research studying senior centres
      has been limited. This scoping review identified English-language empirical
      research studies focusing on senior centres that were published in an academic
      journal in 2000 or later. A total of 58 studies were identified (n = 51 American
      and n = 7 Canadian). The majority of the articles focused on themes related to
      the participation of individuals at senior centres; a smaller number focused on
      themes related to the senior centre environment. Based on the findings, it is
      suggested that future research focus on benefits of senior centre programming,
      with specific focus on needs of baby boomers; key factors related to funding,
      space, and staffing; and the characteristics and role of senior centres in the
      Canadian context.

PMID- 30187838
TI  - The surgical management of bilateral facial paralysis: case report.
AB  - BACKGROUND: Unilateral total facial palsy is a debilitating condition that can
      affect an individual's physical, social and emotional wellbeing. When this occurs
      bilaterally, the severity of impact is extreme, with significant cosmetic
      disfigurement and functional morbidity. A variety of facial reanimation
      techniques have been used for unilateral facial weakness of varying House
      Brackmann grades, and these are also applicable in bilateral cases. In bilateral
      cases, it is difficult to gauge successful improvement in comparison to the
      contralateral side, which also is afflicted.Case reportThis paper presents our
      experience with a bilateral facial paralysis patient who had a complex otological
      history. The patient, who presented with bilateral debilitating grade VI facial
      palsy, achieved a good result from bilateral facial reanimation with sequential
      hypoglossal-facial anastomosis. This is considered a reasonable option in cases
      of bilateral facial paralysis.

PMID- 30187840
TI  - Dietary patterns associated with hypertension risk among adults in Thailand: 8
      year findings from the Thai Cohort Study.
AB  - OBJECTIVE: Dietary intake is a leading risk factor for hypertension. We aimed to
      assess longitudinal associations between overall dietary patterns and incident
      hypertension among adults in Thailand. DESIGN: Prospective large Thai Cohort
      Study (TCS) conducted nationwide from 2005 to 2013. Dietary patterns were
      identified using factor analysis based on usual intake of fourteen food groups.
      Multivariable logistic regression assessed associations between dietary patterns
      and hypertension prevalence and incidence. SETTING: Emerging hypertension and
      changing diets in Thailand. SUBJECTS: TCS participants who were normotensive at
      baseline in 2005. RESULTS: Among 36293 participants without hypertension at
      baseline, 1831 reported incident hypertension (5.1 % incidence) at follow-up. Two
      dietary patterns were identified: 'Modern' and 'Prudent'. The Modern dietary
      pattern (high intakes of roasted/smoked foods, instant foods, canned foods,
      fermented fruits/vegetables, fermented foods, soft drinks, deep-fried foods) was
      associated with increased incident hypertension (comparing extreme quartiles, OR
      for incident hypertension=1.51; 95 % CI 1.31, 1.75 in 2013). The Prudent dietary
      pattern (high intakes of soyabean products, milk, fruits, vegetables) was not
      associated with incident hypertension in a fully adjusted model. The association
      between the Modern dietary pattern and hypertension was attenuated by BMI.
      CONCLUSIONS: Modern dietary pattern was positively associated with hypertension
      among Thai adults. BMI had a great impact on the relationship between the Modern
      dietary pattern and incidence of hypertension. Reduction of Modern diets would be
      expected to prevent and control hypertension. Such a strategy would be worth
      testing.

PMID- 30187842
TI  - Liminality as a dimension of the experience of living with terminal cancer.
AB  - OBJECTIVE: This paper is concerned with the phenomenology of death awareness
      within the context of being diagnosed with terminal cancer. The objective of the
      research presented here is to provide a deeper insight into terminally ill cancer
      patients' engagement with their mortality. METHOD: The analysis forms part of a
      wider project that involved conducting a metasynthesis of 23 phenomenological
      studies of the experience of living with the awareness of having terminal cancer
      published between 2011 and 2016.ResultThe metasynthesis identified four master
      themes that represent distinct experiential dimensions of living with terminal
      cancer. This paper focuses on one of these themes, liminality, to provide novel
      insights into the structure of death awareness whilst living with terminal
      cancer.Significance of resultsThe results suggest that liminality describes an
      experiential space from within which terminal cancer patients encounter a new
      relationship with their existence. Liminality offers opportunities for both
      connection (e.g., with the natural world) as well as disconnection (e.g., from
      loved ones and others who still have a future) and therefore contains the
      potential for suffering and distress as well as for joy and a sense of
      fulfillment. This understanding of liminality can help healthcare professionals
      provide psychological support for this client group.

PMID- 30187843
TI  - Prevalence of Autism Spectrum Disorder in a large Italian catchment area: a
      school-based population study within the ASDEU project.
AB  - : AimsThis study aims to estimate Autism Spectrum Disorders (ASD) prevalence in
      school-aged children in the province of Pisa (Italy) using the strategy of the
      ASD in the European Union (ASDEU) project. METHODS: A multistage approach was
      used to identify cases in a community sample (N = 10 138) of 7-9-year-old
      children attending elementary schools in Pisa - Italy. First, the number of
      children with a disability certificate was collected from the Local Health
      Authority and an ASD diagnosis was verified by the ASDEU team. Second, a Teacher
      Nomination form (TN) to identify children at risk for ASD was filled in by
      teachers who joined the study and the Social Communication Questionnaire (SCQ)
      was filled in by the parents of children identified as positive by the TN; a
      comprehensive assessment, which included the Autism Diagnostic Observation
      Schedule-Second Edition, was performed for children with positive TN and SCQ?9.
      RESULTS: A total of 81 children who had a disability certificate also had ASD
      (prevalence: 0.79%, i.e. 1/126). Specifically, 66 children (57 males and nine
      females; 62% with intellectual disability -ID-) were certified with ASD, whereas
      another 15 (11 males and four females; 80% with ID) were recognised as having ASD
      among those certified with another neurodevelopmental disorder. Considering the
      population of 4417 (children belonging to schools which agreed to participate in
      the TN/SCQ procedure) and using only the number of children certified with ASD,
      the prevalence (38 in 4417) was 0.86%, i.e. one in 116. As far as this population
      is concerned, the prevalence rises to 1% if we consider the eight new cases (six
      males and two females; no subject had ID) identified among children with no pre
      existing diagnoses and to 1.15%, i.e., one in 87, if probabilistic estimation is
      used. CONCLUSIONS: This is the first population-based ASD prevalence study
      conducted in Italy so far and its results indicate a prevalence of ASD in
      children aged 7-9 years of about one in 87. This finding may help regional,
      national and international health planners to improve ASD policies for ASD
      children and their families in the public healthcare system.

PMID- 30187841
TI  - Training for awareness of one's own spirituality: A key factor in overcoming
      barriers to the provision of spiritual care to advanced cancer patients by
      doctors and nurses.
AB  - OBJECTIVE: When patients feel spiritually supported by staff, we find increased
      use of hospice and reduced use of aggressive treatments at end of life, yet
      substantial barriers to staff spiritual care provision still exist. We aimed to
      study these barriers in a new cultural context and analyzed a new subgroup with
      "unrealized potential" for improved spiritual care provision: those who are
      positively inclined toward spiritual care yet do not themselves provide it.
      METHOD: We distributed the Religion and Spirituality in Cancer Care Study via the
      Middle East Cancer Consortium to physicians and nurses caring for advanced cancer
      patients. Survey items included how often spiritual care should be provided, how
      often respondents themselves provide it, and perceived barriers to spiritual care
      provision.ResultWe had 770 respondents (40% physicians, 60% nurses) from 14
      Middle Eastern countries. The results showed that 82% of respondents think staff
      should provide spiritual care at least occasionally, but 44% provide spiritual
      care less often than they think they should. In multivariable analysis of
      respondents who valued spiritual care yet did not themselves provide it to their
      most recent patients, predictors included low personal sense of being spiritual
      (p < 0.001) and not having received training (p = 0.02; only 22% received
      training). How "developed" a country is negatively predicted spiritual care
      provision (p < 0.001). Self-perceived barriers were quite similar across
      cultures.Significance of resultsDespite relatively high levels of spiritual care
      provision, we see a gap between desirability and actual provision. Seeing oneself
      as not spiritual or only slightly spiritual is a key factor demonstrably
      associated with not providing spiritual care. Efforts to increase spiritual care
      provision should target those in favor of spiritual care provision, promoting
      training that helps participants consider their own spirituality and the role
      that it plays in their personal and professional lives.

PMID- 30187844
TI  - Hemophagocytic Lymphohistiocytosis Complicating Melioidosis.

PMID- 30187845
TI  - Remembering Arthur: A Tale of Resilience in Malawi.

PMID- 30187846
TI  - Poverty, Genocide, and Superbugs: A Carbapenem-Resistant Wound Infection in Rural
      Guatemala.

PMID- 30187847
TI  - Trichuris trichiura-An Unwelcome Surprise during Colonoscopy.

PMID- 30187848
TI  - Erratum.

PMID- 30187850
TI  - ?

PMID- 30187849
TI  - ?

PMID- 30187851
TI  - [Harlequin ichthyosis with a diaphragmatic hernia and a new mutation].
AB  - Harlequin ichthyosis (HI) is a rare and severe form of the autosomal recessive
      congenital ichthyosis. This is a case report of a 30-year-old healthy woman with
      a pregnancy resulting in preterm birth of a child with severe HI, who did not
      survive. At the autopsy, the child was found with HI and a diaphragmatic hernia
      of the Bochdalek type. Genetic analysis showed, that the child was homozygous for
      the mutation c.5121_5124del in ABCA12. The parents were related and were found
      heterozygous of this mutation. This clinical presentation with this new mutation
      has not been described in the literature before.

PMID- 30187852
TI  - [Wilkie's syndrome as the cause of stomach pain in a young woman].
AB  - Wilkie's syndrome is a rare condition in which a decreased angle and distance
      between the superior mesenteric artery and aorta causes a compression of the
      third part of the duodenum, resulting ultimately in gastric dilation, gastric
      rupture and acute ischaemia of the bowel. The early symp-toms are those of
      duodenal obstruction. It is clinically char-acteristic, easily recognised on
      diagnostic imaging and is treated either conservatively or surgically. Although
      rare, Wilkie's syndrome is associated with severe morbidity, and should be
      considered in patients presenting with abdominal pain.

PMID- 30187853
TI  - [Intramural duodenal haematoma after endoscopic injection therapy of a bleeding
      ulcer].
AB  - In this case report a 48-year-old man presented with nausea and abdominal pain.
      Ten days prior he had been treated with an endoscopic epinephrine/saline
      injection for haemostasis of a bleeding duodenal ulcer and was discharged the
      following day. At readmission, an abdominal CT revealed severe gastric distention
      and a gastroscopy showed total duodenal obstruction. Subsequent post-contrast CT
      revealed that a massive intramural duodenal haematoma was the cause of the total
      duodenal occlusion. Also, acute pancreatitis was seen. The treatment was
      conservative, and follow-up gastroscopy showed total resolution of the haematoma.

PMID- 30187854
TI  - [Cardiac magnetic resonance imaging in evaluation of cardiomyopathies].
AB  - The cardiomyopathies are a heterogeneous group of disorders primarily having
      myocardial dysfunction in common. Phenotypical classification relies on
      morphological and functional criteria. Cardiac magnetic resonance imaging (CMR)
      has advanced into an imaging modality, which allows assessment of structure and
      function in addition to myocardial tissue characterization and evaluation of the
      myocardial iron content, inflammation and fibrosis. This review describes the
      status of CMR for evaluation of cardiomyopathies.

PMID- 30187855
TI  - [Classification of vascular anomalies].
AB  - The classification of vascular anomalies has been revised, as physicians and
      researchers have recognised an increasing number of vascular anomalies. The
      International Society for the Study of Vascular Anomalies presents a
      classification distinguishing between tumours and malformations. Over the years,
      an inaccurate application of the term haemangioma has been used, which has led to
      confusion among physicians. By using the classification and combining it with a
      thorough history and objective examination a classification of the most common
      vascular anomalies should be possible.

PMID- 30187856
TI  - [Rectal foreign bodies].
AB  - Rectal foreign bodies are not uncommon as previously thought and should be
      recognised as a potentially serious condition. The diagnosis is often delayed due
      to patient embarrassment and reluctance to seek medical help, which may increase
      the likelihood of complications. Clinicians should be aware of this condition, as
      it may be a manifestation of underlying psychiatric conditions, drug trafficking
      or due to sexual assault.

PMID- 30187857
TI  - Nationwide cross-sectional study of Danish surgeons' professional use of social
      media.
AB  - INTRODUCTION: The extent of professional social media (SM) engagement by Danish
      surgeons remains unknown. It may be important for Danish surgeons to engage in
      SM, not only to establish and maintain an international network, but also to stay
      up to date on new developments in the international surgical community. The aim
      of the present study was to describe Danish surgeons' professional engagement in
      SM. METHODS: This was a descriptive cross-sectional study surveying all
      registered Danish surgeons who were members of the Danish Medical Association by
      May 2017. An online questionnaire was sent to all identified surgeons twice eight
      days apart. The questionnaire contained questions about the use of SM for
      professional purposes. RESULTS: The total response rate was 40.8%. After
      exclusion of non-active surgeons, a total of 261 respondents were included in the
      study. Of these, 81 (30.0%) reported to be engaged in SM professionally. Surgeons
      actively using SM professionally were younger (mean age 53.8 versus 57.6 years, p
      = 0.018) and had more often been scientifically active within the past year
      (64.1% versus 48.6%, p = 0.032) compared with surgeons who were not using SM
      professionally. Of those who were not engaged in SM professionally, 33 (18.3%)
      replied that they would consider using SM for professional purposes if they
      received help in doing this. CONCLUSIONS: One third of surgeons in Denmark seem
      to be actively engaged in SM for professional purposes. The findings of the
      present study suggest that a potential for further SM involvement exists.
      FUNDING: none. TRIAL REGISTRATION: none.

PMID- 30187858
TI  - LED virtual windows are valuable in windowless consultation rooms.
AB  - INTRODUCTION: Due to the design of Hvidovre Hospital, the outpatient clinic of
      the Department of Paediatrics has windowless consultation rooms. Work environment
      surveys revealed that nurses and doctors working in these windowless rooms
      considered the lack of natural light a considerable health problem. This study
      evaluated the effects of installing light-emitting diode (LED) virtual windows in
      these rooms. METHODS: Four similar windowless consultations rooms located next to
      each other were used in the study. All had older T-5 fluorescent luminaires
      installed. In two of these rooms, Servodan LED virtual windows depicting various
      natural scenes were installed. The illuminance and correlated colour temperature
      (CCT) of each room's lighting was measured, and a work environment questionnaire
      was filled out by nurses and doctors working in each room. RESULTS: A total of
      113 questionnaires were collected and evaluated. LED virtual windows produced an
      improved perception of lighting conditions, both at the desk (p < 0.001) and in
      the rooms in general (p < 0.001) and improved the overall positive experience of
      the rooms (p = 0.02). A tendency towards concentration difficulties was reported
      less often in the rooms with LED virtual windows, (p = 0.11). Retinal illuminance
      (p = 0.02) as well as CCT at the desk (p < 0.005) and at the retina (p < 0.01)
      alike were increased in rooms with LED virtual windows. CONCLUSIONS: LED virtual
      windows improved the lighting experience, the impression of the space, the
      retinal illuminance and the CCT at the desk and at the retina in the windowless
      rooms. FUNDING: none. TRIAL REGISTRATION: not relevant.

PMID- 30187859
TI  - A SWOT analysis of how the youngest doctors perceive the formal Danish
      educational advisory programme.
AB  - INTRODUCTION: A national formal advisory programme (NFAP) was introduced in
      Denmark in 1998. This study investigates the implementation of the NFAP and
      identifies areas to improve. METHODS: In March 2017, a survey was conducted among
      all 129 doctors employed in the first rotation of postgraduate medical education
      in the Central Denmark Region. A priority chart was created to appoint strengths,
      weaknesses, op-portunities and threats (SWOT). RESULTS: The response rate was
      67%. The questionnaire showed good reliability and discriminant validity. Almost
      all respondents had completed the recommended appraisal meetings and a personal
      learning plan, both of which - in contrast to the NFAP's coherence to everyday
      clinical practice - showed to have much influence on the overall value of the
      NFAP. Strengths found were that appraisal meetings and learning plans support the
      development of clinical competencies, the latter identifying learning objectives
      and how to achieve them. Threats identified included learning plans that were not
      prepared sufficiently early, were not regularly adjusted and that did not
      describe when each learning objective is to be achieved, or when, by whom or how
      assessment will take place. CONCLUSIONS: Appraisal meetings and learning plans
      seem to be well implemented and to support the development of clinical
      competencies. Even so, improvements are needed, particularly to ensure an earlier
      preparation, inclusion of plans for assessment and regular adjustment of the
      learning plans. FUNDING: The study was funded by the Central Denmark Region.
      TRIAL REGISTRATION: Data collection was approved by the Danish Health Data
      Authority.

PMID- 30187860
TI  - Optimisation of quality indicators for lipid-lowering treatment of type 2
      diabetes mellitus.
AB  - INTRODUCTION: The Danish Adult Diabetes Database (DADD) annually reports a
      quality indicator for lipid-lowering treatment of type 2 diabetes mellitus (T2DM)
      patients. This retrospective cohort study aims to A) investigate the reasons for
      inadequate or lacking lipid-lowering treatment and to B) assess the validity of
      the DADD indicator as a measure of quality of care. METHODS: A) A pop-up
      questionnaire enquiring about reasons for lack of treatment was added to the
      clinicians' data entry tool in the Central Denmark Region. B) The DADD indicator
      was compared on a per-clinic basis with the achieved median low-density
      lipoprotein (LDL) cholesterol level and with an internationally widely used
      indicator of lipid-lowering treatment quality. RESULTS: A) A total of 3,491
      patients were registered from 1 January 2013 to 28 February 2015. For 170 (62%)
      of 309 patients with an LDL level > 2.5 mmol/l who were not receiving lipid
      lowering treatment, there was no "good" explanation for lacking treatment. Among
      518 patients with an LDL level > 2.5 mmol/l despite lipid-lowering treatment, 259
      (50%) did not receive high-intensity treatment. B) The DADD quality indicator was
      neither associated with the international quality indicator nor with the median
      per-clinic LDL level for T2DM patients. CONCLUSIONS: A) We found substantial
      potential for improvement of lipid management among T2DM patients in Denmark by
      initiating and/or intensifying lipid-lowering treatment. B) The current DADD
      indicator is not a valid measure of lipid-lowering quality of care. FUNDING:
      supported by the Rosa and Asta Jensen Foundation. TRIAL REGISTRATION: not
      relevant.

PMID- 30187861
TI  - The Danish translation and validation of the Berlin Questionnaire for sleep
      apnoea.
AB  - INTRODUCTION: Obstructive sleep apnoea (OSA) is an increasing health problem
      related to cardiovascular disease, poor quality of life, daytime sleepiness and
      un-restorative sleep with an estimated prevalence up to 20% in the adult
      population. Approximately 82% of men and 93% of women with moderate to severe OSA
      remain undiagnosed. Relevant, fast, accurate and cost-effective screening methods
      are essential. The aim of this study was to translate and validate the Danish
      version of the Berlin Questionnaire (BQ), and to investigate if the questionnaire
      can be used for screening of OSA in a Danish population. METHODS: The BQ was
      translated into Danish according to guidelines producing the Danish Berlin
      Questionnaire (DBQ). The study population included 206 adult patients referred to
      the Sleep Clinic of Zealand University Hospital, Denmark, on suspicion of OSA.
      RESULTS: 69.4% were males, 53.3% were obese (BMI > 30), the mean BMI was 32.01. A
      total of 135 patients had hypertension (65.5%). Apnoea/hypopnoea Index (AHI) >=
      15 was present in 141 of 206 patients (68.4%). We observed a sensitivity of the
      DBQ of 84% and a positive predictive value of 69%. CONCLUSIONS: We have
      successfully translated and partially validated the DBQ for OSA. Our study showed
      that the DBQ is useful for screening of Danish patients suspected of OSA. Further
      studies with improved screening methods and further development of questionnaires
      are recommended. FUNDING: none. TRIAL REGISTRATION: The study was approved by the
      Danish Data Protection Agency.

PMID- 30187862
TI  - Regional variation in surgery for pancreatic cancer in Denmark 2011-2015.
AB  - INTRODUCTION: Surgical treatment for pancreatic cancer carries a high risk of
      both morbidity and mortality. Even so, it remains the best curative treatment
      option. In Denmark, pancreatic surgery has been extensively centralised since the
      millennium, but the effect of this centralisation on patient outcome has not been
      evaluated. This study describes regional variation within pancreatic surgery on a
      malignant indication, focusing on production volume, length of stay, readmission
      rates and mortality. METHODS: This is a retrospective cohort study of all
      patients with pancreatic cancer who underwent surgical treatment in Denmark from
      2011 to 2015. We obtained data from the Danish National Patient Registry and the
      National Pathology Data Bank on length of stay, transfers, mortality (both short
      and long term), age, co-morbidity, and disease stage. RESULTS: Four hospital
      units performed a total of 691 surgical procedures (476
      pancreaticoduodenectomies) in the study period. Production volume varied
      considerably across units with two units accounting for nearly 80% of surgery
      performed. Data revealed variation on rates of transfers and readmissions as well
      as disease stage and mortality (both short and long term). CONCLUSIONS: Data
      suggest that mortality is linked to production volume as well as disease stage,
      but the small data quantity impedes rigorous statistical analysis. Further
      studies on the observed associations are required. FUNDING: none. TRIAL
      REGISTRATION: not relevant.

PMID- 30187864
TI  - The safety and efficacy of four different fixed combination regimens of adapalene
      0.1%/benzoyl peroxide 2.5% gel for the treatment of acne vulgaris: results from a
      randomised controlled study.
AB  - BACKGROUND: Combined use of a retinoid and antimicrobial is recommended for acne,
      however, local tolerability issues may compromise patient adherence and treatment
      outcome. OBJECTIVES: This multicentre, single-blinded controlled study was
      designed to determine whether modified adapalene/benzoyl peroxide (A/BPO,
      Epiduo(r), Galderma, France) regimens improve local tolerability during the first
      four weeks of treatment without impairing efficacy at Week 12. MATERIALS &
      METHODS: In total, 120 subjects with mild-to-moderate acne received, during the
      first four weeks, A/BPO daily overnight (A/BPO-EN), A/BPO daily for three hours
      (A/BPO-3h), A/BPO daily overnight and a provided moisturizer lotion (A/BPO
      moisturizer), or A/BPO every other night (A/BPO-EoN). Local tolerance assessments
      included signs and symptoms, global worst score (GWS), and total sum score (TSS).
      Efficacy was assessed based on lesion counts, investigator global assessment
      (IGA), and total lesion count reduction. Adherence, subject satisfaction, and
      overall safety were also assessed. RESULTS: The mean TSS was significantly
      reduced at Week 1 with A/BPO-EoN vs. A/BPO-EN (p<0.05), and A/BPO-EoN led to the
      lowest GWS and a decrease in severity of stinging/burning and erythema (p<0.05).
      The A/BPO-moisturizer regimen prevented dryness and scaling compared with the
      A/BPO-EN regimen. The median decrease in lesions from baseline was similar in all
      groups: up to 67% for total, 72% for inflammatory, and 70% for non-inflammatory
      lesion counts. Adherence, IGA, patient satisfaction, and overall safety were
      excellent. CONCLUSIONS: Modulating treatment regimens during the first four weeks
      improved local tolerability without impacting overall efficacy outcome after 12
      weeks and may improve treatment adherence during the first weeks of therapy.

PMID- 30187865
TI  - [Risk factors for surgical site infection following posterior lumbar
      intervertebral fusion].
AB  - OBJECTIVE: To analyze the risk factors of surgical site infection (SSI) following
      posterior lumbar intervertebral fusion. METHODS: This retrospective case-control
      study was conducted in 2904 patients undergoing posterior lumbar intervertebral
      fusion from 2011 to 2016. Forty-three patients with SSI within 30 days after the
      operation served as the case group, and 334 randomly selected patients without
      infection served as the control group. Age, gender, diabetes, body mass index
      (BMI), albumin level, multilevel procedures, subcutaneous fat thickness, surgery
      duration and the percentage of lumbar multifidus muscle fat infiltration were
      analyzed, and univariate and multivariate logistic regression analyses were
      performed to identify the risk factors of SSI. RESULTS: Multivariate logical
      regression analysis identified a female gender, subcutaneous fat thickness,
      multilevel surgery, and lumbar multifidus muscle fat infiltration as significant
      risk factors for SSI (P < 0.05). BMI was not correlated with fat infiltration in
      the lumbar multifidus muscle (P > 0.05). CONCLUSIONS: A female gender, multilevel
      surgery, subcutaneous fat thickness and fat infiltration in the multifidus muscle
      are related to SSI following posterior lumbar intervertebral fusion. Fat
      infiltration in the multifidus muscle was a spine-specific risk factor for SSI
      independent of BMI.

PMID- 30187866
TI  - [Activation of aldehyde dehydrogenase 2 alleviates H 2O 2-induced injury in
      cardiomyocytes].
AB  - OBJECTIVE: To investigate the changes of aldehyde dehydrogenase 2 (ALDH2)
      expression in H 2O 2inducedcardiomyocytes oxidative stress injury. METHODS:
      Cultured H9C2 cardiomyocytes were exposed to H 2O 2-inducedoxidative stress and
      the effects of the ALDH2 agonist Alda-1 and ALDH2 inhibitor Daidzin were tested
      on the stress level ofthe exposed cells. MTT colorimetric assay was used to
      assess the cell viability after the treatments. The oxidative stress level inthe
      myocardial cells was detected using DHE fluorescence staining, and the activity
      and protein level of ALDH2 were detectedwith spectrophotometry and Western
      blotting. RESULTS: Compared with normal control cells, Alda-1 treatment did
      notsignificantly affect the cell viability, oxidative stress level, or ALDH2
      activity and protein level. H 2O 2 exposure significantlylowered the cell
      activity and ALDH2 activity and protein expression and increased the oxidative
      stress level; Alda-1 treatmentobvious antagonized the effects of H 2O 2. Blocking
      ALDH2 with Daidzin produced similar effects to H 2O 2 exposure on theviability,
      oxidative stress level, and ALDH2 activity and expression in the myocardial
      cells. CONCLUSIONS: H 2O 2 exposure lowersthe activity and reduces the protein
      expression of ALDH2 in cardiomyocyte H9C2 cells, and activation of ALDH2 can
      alleviateH 2O 2-induced oxidative stress in the cells.

PMID- 30187867
TI  - [USP33 suppresses lung adenocarcinoma lung cell invasion and metastasis by down
      regulating SLIT2/ROBO1 signaling pathway].
AB  - OBJECTIVE: To investigate the role of USP33 as an independent prognostic marker
      in the regulation of SLIT2/ROBO1 signaling pathway to inhibit lung adenocarcinoma
      invasion and metastasis. METHODS: The expression of USP33 in 20 lung
      adenocarcinoma specimens was detected by qPCR and immunohistochemistry. A549 and
      SPC-A-1 cells with small interfering RNA (siRNA)-mediated USP33 silencing were
      examined for changes in invasion and metastasis abilities using scratch assay and
      Matrigel assay. Western blotting was used to detect the expression of SLIT2 and
      ROBO1 in the cells after USP33 silencing and the expression of USP33 after
      interleukin-6 (IL-6) stimulation. RESULTS: qPCR and immunohistochemistry showed
      that USP33 was significantly decreased in lung adenocarcinoma tissues as compared
      with the adjacent tissues. USP33 silencing in A549 and SPC-A-1 cells
      significantly promoted the cell migration, invasion and metastasis and obviously
      down-regulated the expressions of SLIT2 and ROBO1. IL-6 stimulation of the cells
      obviously enhanced the expression of USP33. CONCLUSIONS: USP33 silencing can
      promote the migration, invasion and metastasis of lung adenocarcinoma cells in
      vitro, and the mechanism may involve IL-6 and SLIT2/ROBO1 signaling pathways.

PMID- 30187868
TI  - [Differences in expression profiles of circular RNA between luminal breast cancer
      cells and normal breast cells].
AB  - OBJECTIVE: To investigate the differences in the expression profiles of circular
      RNA (circRNA) between luminal breast cancer cells and normal breast cells.
      METHODS: Total RNA extracted from luminal breast cancer cells MCF7 and normal
      breast cells MCF10A was digested with Rnase R to remove linear RNAs and enrich
      circRNAs. The enriched circRNAs were amplified and transcribed into fluorescent
      cRNAs using a random priming method, and were hybridized onto the circRNA
      hybridization array. The circRNA expression profiles of MCF7 and MCF10A cells
      were analyzed using Agilent Feature Extraction software. Quantile normalization
      and subsequent data processing were performed, and volcano plot filtering and
      hierarchical clustering were utilized to analyze the circRNA expression patterns.
      The expressions of 3 circRNAs with significant log fold changes were validated
      using qPCR. RESULTS: The hybridization array data revealed significant
      differences in the circRNA expression profiles between MCF7 and MCF10A cells.
      Compared with those of MCF10A cells, the 12910 circRNAs expressed in MCF7 cells
      showed 5964 up-regulated, 81 consistently regulated, and 6865 down-regulated
      circRNAs; 343 circRNAs showed a log fold change by more than 2 folds, among which
      213 circRNAs were up-regulated and 130 were down-regulated. Nine circRNAs showed
      differential expressions by more than 2 folds, including 8 up-regulated ones,
      namely hsa_circRNA_061260 (6.02 folds), hsa_circRNA_103933 (5.96 folds),
      hsa_circRNA_005239 (5.84 folds), hsa_circRNA_100689 (5.69 folds),
      hsa_circRNA_004087 (5.60 folds), hsa_circRNA_104420 (5.25 folds),
      hsa_circRNA_104421 (5.13 folds) and hsa_circRNA_101222 (5.03 folds); only one
      circRNA was down-regulated, namely hsa_circRNA_104864 (5.09 folds). The
      expressions of hsa_circRNA_100689, hsa_circRNA_005239 and hsa_circRNA_104864 were
      further validated by qPCR, which yielded consistent results with the microarray
      data. CONCLUSIONS: The circRNA expression profiles differ significantly between
      luminal breast cancer cells and normal breast cells. These differentially
      expressed circRNAs may serve as potential novel targets for the diagnosis of
      luminal breast cancer.

PMID- 30187863
TI  - Differential requirement of kindlin-3 for T cell progenitor homing to the non
      vascularized and vascularized thymus.
AB  - The role of integrin-mediated adhesion during T cell progenitor homing to and
      differentiation within the thymus is ill-defined, mainly due to functional
      overlap. To circumvent compensation, we disrupted the hematopoietic integrin
      regulator kindlin-3 in mice and found a progressive thymus atrophy that is
      primarily caused by an impaired homing capacity of T cell progenitors to the
      vascularized thymus. Notably, the low shear flow conditions in the vascular
      system at midgestation allow kindlin-3-deficient fetal liver-derived T cell
      progenitors to extravasate via pharyngeal vessels and colonize the avascular
      thymus primordium. Once in the thymus, kindlin-3 promotes intrathymic T cell
      proliferation by facilitating the integrin-dependent crosstalk with thymic
      antigen presenting cells, while intrathymic T cell migration, maturation into
      single positive CD4 and CD8 T cells and release into the circulation proceed
      without kindlin-3. Thus, kindlin-3 is dispensable for integrin-mediated T cell
      progenitor adhesion and signalling at low and indispensable at high shear forces.

PMID- 30187870
TI  - [Correlation of apolipoprotein AI, apolipoprotein B and their ratio with the
      severity of cerebral white matter lesions].
AB  - OBJECTIVE: To investigate the correlation of apolipoprotein AI (ApoAI), ApoB,
      ApoB/ApoAI and the severity of brain white matter lesions (WML). METHODS: A total
      of 648 patients with WML confirmed by brain magnetic resonance imaging (MRI) were
      divided into mild WML group (n=386) and moderate to severe WML group (n=262)
      according to evaluations with the Fazekas scale. The demographic data, blood
      biochemical parameters and the levels of ApoAI, ApoB and ApoB/AI ratio were
      compared between the two groups to identify the risk factors of moderate to
      severe WML. RESULTS: Univariate analysis showed that age, gender, hypertension,
      diabetes, coronary heart disease, previous stroke, homocysteine, HDL-C, ApoAI,
      and ApoB/AI ratio all differed significantly between the two groups (P < 0.05),
      but ApoB levels were similar between them (P > 0.05). Multivariate logistic
      regression analysis revealed that with ApoAI and ApoB/AI ratio as the continuous
      variables, after adjustment for the compounding factors, ApoB/AI ratio was an
      independent risk factor (OR=11.456, 95% CI: 3.622-36.229, P < 0.001) and ApoAI
      was an independent protective factor for moderate to severe WML (OR=0.068, 95%
      CI: 0.018-0.262, P < 0.001). With the upper quartiles of ApoAI level (1.38 g/L)
      and ApoB/AI ratio (0.58) as their respective cutoff values, patients with a high
      ApoAI level and a low ApoB/AI ratio were found to have the lowest incidence of
      moderate to severe WML (P < 0.001). CONCLUSIONS: An increased ApoB/AI ratio is an
      independent risk factor and an increased ApoAI level is an independent protective
      factor for moderate to severe WML.

PMID- 30187869
TI  - [Expression of interleukin-9 in colon cancer tissues and its clinical
      significance].
AB  - OBJECTIVE: To investigate the expression of interleukin-9 (IL-9) in colon cancer
      tissues and its clinical significance. METHODS: Immunohistochenmistry and qRT-PCR
      were used to detect the expressions of IL-9 protein and mRNA in 92 colon cancer
      tissues and paired adjacent normal tissues. The correlation of IL-9 expressions
      with the clinicopathological features and prognosis of the patients was analyzed.
      RESULTS: IL-9 protein and mRNA expressions were significantly higher in adjacent
      normal tissues than in the colon cancer tissues (P < 0.001). In colon cancer
      patients, IL-9 expression was significantly correlated with TNM stage (P=0.013),
      Ducks stage (P=0.025) and lymph node metastasis (P=0.004) but not with gender,
      age, tumor size, differentiation or hepatic metastasis (P > 0.05). The survival
      time of colon cancer patients with positive IL-9 expression was significantly
      longer than that of patients negative for IL-9 expression (P=0.015). CONCLUSIONS:
      IL-9 expression is lowered in colon cancer tissues compoved with in the adjacent
      normal tissues. IL-9 expression is negatively correlated with TNM staging, Ducks
      staging and lymph node metastasis but positively with good prognosis, suggesting
      its important role in the tumor microenvironment of colon cancer.

PMID- 30187871
TI  - [Biejiajian Pills inhibits hepatoma carcinoma cell vasculogenic mimicry by
      suppressing RhoA/ROCK signaling pathway].
AB  - OBJECTIVE: To observe effects of Biejiajian Pills on hepatocarcinoma (HCC) cell
      vasculogenic mimicry (VM) and explore the molecular mechanism by which Biejiajian
      Pills inhibits HCC metastasis and invasion. METHODS: Forty male SD rats were
      randomly divided into 4 groups for gastric lavage of normal saline or high,
      moderate or low doses of Biejiajian Pills (twice daily) for 4 consecutive days.
      The sera were collected from the rats for treatment of cultured human HCC HepG2
      cells. VM formation in the cells was detected using an image acquisition and
      analysis system 24 h after incubation of the cells with the sera and with the
      RhoA/ROCK inhibitor Y-27632(P). The expression levels of RhoA and ROCK1 in the
      cells were detected using Western blotting, and the contents of VE-cadherin and
      PI3K in the culture supernatant were determined using ELISA. RESULTS: Treatment
      with the sera from Biejiajian Pills-treated rats significantly inhibited
      formation of VM in HepG2 cells, and the diameters of VM formed were significantly
      greater than those in the positive control group (P < 0.01). Y-27632 completely
      inhibited the formation of VM in HepG2 cells (P < 0.01). Treatments with
      Biejiajian Pills and Y-27632 both inhibited the expression of RhoA and ROCK1 (P <
      0.05) and significantly lowered the contents of VE-cadherin and PI3K in the
      culture supernatant (P < 0.05). CONCLUSIONS: Biejiajian Pills can inhibit the
      formation of VM in HCC cells in vitro possibly by inhibiting the RhoA/ROCK
      pathways and the expressions of VE-cadherin and PI3K.

PMID- 30187872
TI  - [Efficacy and metabolic safety of long-term treatment with ethinyl
      oestradiol/cyproterone and desogestrel/ethinyl oestradiol tablets in women with
      polycystic ovary syndrome].
AB  - OBJECTIVE: To evaluate the efficacy and metabolic safety of long-term treatment
      with ethinyl oestradiol/cyproteroneand desogestrel/ethinyl oestradiol tablets in
      women with polycystic ovary syndrome (PCOS). METHODS: Women with PCOSfrom West
      China Second Hospital of Sichuan University enrolled between September, 2011 and
      August, 2013 were randomlyallocated to receive either ethinyl
      oestradiol/cyproterone tablets (Group A, n=355) or desogestrel/ethinyl oestradiol
      tablets(Group B, n=357) for a prospective observation period of 6 months. Women
      with insulin resistance also received metformin. Atbaseline, 3 months, and 6
      months, the patients were evaluated for menstruation, acne score, body mass index
      (BMI), waist-tohip ratio (WHR), plasma levels of sex hormones, fasting blood
      glucose (FPG), HOMA-insulin resistance index (HOMA-IR), serum lipid, ovarian
      volume, and the number of ovarian follicles. RESULTS: All the patients had a
      regular menstrual cycle aftertreatments. Testosterone level, acne score, LH/FSH,
      ovarian volume, and the number of follicles decreased significantly afterthe
      treatments without significant differences between the two groups. Significant
      increases were noted in TG, TCh, LDL, HDL, and AIP, and HDL level in group A as
      compared with group B (P < 0.001). FPG decreased in both groups, and
      wassignificantly lower in group B at 6 months (P < 0.05). BMI and WHR decreased
      in all the patients with insulin resistance aftercombination treatment with
      metformin (P < 0.05), but increased significantly in patients without insulin
      resistance (P < 0.05). Ingroup A, HOMA- IR significantly increased in
      patientswithout insulin resistance at 3 months (P < 0.05), whereas asignificant
      increase was not observed until 6 months ingroup B (P < 0.05). CONCLUSIONS: Both
      ethinyl oestradiol/cyproterone tablets and desogestrel/ethinyl oestradioltablets
      can relieve the symptoms of PCOS, but it isadvisable to assess the risk of
      cardiovascular diseasebefore the treatments.

PMID- 30187873
TI  - [Retinal transcriptome profile in mice following dexamethasone treatment for
      endotoxin-induced uveitis].
AB  - OBJECTIVE: To investigate the changes in retinal transcriptome profile of mice
      with endotoxin-induced uveitis (EIU)following dexamethasone (DEX) treatment and
      explore the mechanisms underlying the therapeutic effect of DEX. METHODS: EIU was
      induced in BALB/c mice by intravitreal injection of 125 ng lipopolysaccharide
      (LPS), followed by topical applicationof DEX (0.1%) eye drops every 4 h for 24 h.
      The anterior chamber inflammation was examined with a slit lamp and the
      clinicalscores were assessed. The morphological changes in the eyes were assessed
      at 24 h after LPS injection. The retinas wereharvested for analysis of
      transcriptome profile using the next-generation sequencing (NGS)-based RNA
      sequencing (RNA-seq), and the expressions of the inflammatory cytokines and the
      differentially expressed genes (DEGs) were verified using real-timePCR. RESULTS:
      DEX alleviated the inflammatory response and reduced the mRNA expressions of IL
      6, TNF- a, MCP-1 andICAM-1 at 24 h after LPS injection. A total of 52 DEGs were
      identified by RNA-seq. Within these DEGs, 37 genes were upregulated and 15 genes
      were down-regulated in LPS group as compared with DEX+LPS group. No significantly
      enriched GeneOntology (GO) terms was noted. Kyoto Encyclopedia of Genes and
      Genomes (KEGG) pathway enrichment analysis showed 6up-regulated and 2 down
      regulated KEGG pathways. RIG-I-like receptor signaling pathway and several immune
      andinflammation-related genes including Ifit1, H2-T24, Mx2 and Eif2ak2 were
      significantly down regulated by DEX. Verificationwith RT-PCR yielded results
      consistent with these findings. CONCLUSIONS: DEX alleviates LPS-induced
      inflammatory response inthe retina of mice, and such protective effect is
      probably mediated by RIG-I like receptor signal pathway and the immune
      andinflammation-related genes.

PMID- 30187874
TI  - [Adenoid cystic carcinoma cells produce exosomes that promote tumor cell
      proliferation].
AB  - OBJECTIVE: To observe the effect of exosomes released by adenoid cystic carcinoma
      (ACC) cell line SACC-83 on the proliferation of ACC cells. METHODS: Exosomes were
      isolated from SACC-83 cell culture supernatants using total exosome isolation
      reagents. The whole-mount exosomes were characterized using transmission electron
      microscope and Western blotting. The exosomes were labeled with green fluorescent
      dye PKH67 and co-cultured with SACC-83 cells for 48 h, followed by staining with
      Alexa Fluor 594 phalloidin and DAPI to observe exosome uptake by the cells using
      laser scanning confocal microscopy (LSCM). The cell proliferation was assessed
      using MTT assay and wound healing assay, and the expressions of ERK and P-ERK in
      the co-cultured SACC-83 cells were detected using Western blotting. RESULTS: The
      exosomes isolated from SACC-83 cells showed a size range of 30-100 nm and
      expressed the exosomal markers CD9, CD63 and TSG101. LSCM showed exosome uptake
      by SACC-83 cells, which exhibited accelerated proliferation and significantly
      enhanced P-ERK expression (P < 0.05) without significant changes in ERK
      expression. CONCLUSIONS: SACC-83 cells produce exosomes that promote the tumor
      cell proliferation and enhances the cellular expression of P-ERK, suggesting a
      potential role of MAPK/ERK pathway activation in exosome-mediated acceleration of
      ACC cell proliferation.

PMID- 30187875
TI  - [Correlation between TGF-B gene promoter-509C/T polymorphism and IgA nephropathy
      in core families in Guangxi Zhuang Autonomous Region and the therapeutic effect
      of dendrobium].
AB  - OBJECTIVE: To investigate the correlation between transformation growth factor
      (TGF- B) polymorphisms and IgA nephropathy and the therapeutic effect of
      dendrobium on IgA nephropathy. METHODS: Polymerase chain reaction- restriction
      fragment length polymorphism (PCR- RFLP) and direct sequencing were used for
      analysis of 118 patients with IgA nephropathy from core families in Guangxi
      Zhuang Autonomous Region. The imbalanced transfer of TGF iso1-509 C/T in the
      affected offsprings was observed by transfer imbalance test and HRR analysis. The
      TGF-B genotype of the patients and the core family members were detected. The
      therapeutic effects of Dendrobium candidum combined with hormone and ACEI/ARB
      treatments were evaluated by observing the patient's urine protein (24 hUpr),
      serum albumin (ALB), creatinine (Scr) and urea nitrogen (BUN) levels. RESULTS: In
      the 118 patients with IgA nephropathy, we identified TGF-B 1 promoter -509C/T
      genotype CC in 32 (27.1%) cases, CT in 58 (49.2%) cases, and TT in 28 (23.7%)
      cases. In the core family of the patients, CC genotype was found in 33 (28.0%)
      cases, CT in 55 (46.6%) cases, and TT in 30 (28.0%) cases. The treatments
      significantly lowered 24 hUpr, Scr, and BUN levels (P > 0.05) in patients with CC
      genotype, significantly lowered 24 hUpr and BUN levels in patients with CT
      genotype (P < 0.05), and significantly lowered 24 hUpr and BUN level and
      increased (P < 0.05) ALB level (P < 0.01) in patients with TT genotype.
      CONCLUSIONS: There is no significant correlation between TGF-B promoter - 509C/T
      polymorphism and IgA nephropathy. The patients with CC genotype are sensitive to
      the treatments with hormone and ACEI/ ARB and show a stronger response to
      combined treatments with dendrobium.

PMID- 30187876
TI  - [Role of poly(ADP-ribose) polymerases-1-mediated blockade of autophagy in
      ischemia/reperfusion injury of rat cardiomyocytes].
AB  - OBJECTIVE: To investigate the role of poly(ADP-ribose) polymerases-1 (PARP-1)
      mediated blockade of autophagic flow in myocardial ischemia-reperfusion injury.
      METHODS: H9c2 cells, a rat cardiac myocyte line, were divided into control group,
      hypoxia/ reoxygenation model group (H/R group), PARP-1 inhibitor (PJ34) group,
      and PJ34 + H/R group. The total protein was extracted from the cells in each
      group to detect the expressions of pADPr, Bax, the DNA damage marker protein p
      YH2ax, and autophagic flow-associated proteins LC3BII/LC3I, Beclin-1, and P62
      using Western blotting. RESULTS: Compared with the control cells, the cells with
      H/R exhibited significantly increased expressions of pADPr, Bax and p-YH2ax (P <
      0.05). The expressions of LC3B II, beclin-1 and p62 were also increased
      significantly in the cells with H/R (P < 0.05), indicating the block of the
      autophagic flow. The application of PARP-1 inhibitor PJ34 in the cells with H/R
      significantly inhibited the expressions of pADPr (P < 0.05) and Bax (P < 0.01),
      and alleviated DNA damage in the cells. PJ34 treatment did not cause significant
      changes in the expressions of LC3B II and beclin-1 but significantly decreased
      the expression of p62 (P < 0.05) in the cells with H/R. CONCLUSIONS: Block of
      autophagic flow mediated by PARP-1 activation plays a role in myocardial
      ischemiareperfusion injury, and inhibition of PARP-1 activity can reverse
      autophagic flow block to reduce the injury.

PMID- 30187877
TI  - [2-deoxyglucose inhibits angiogenesis of rheumatoid arthritis via activating AMPK
      pathway].
AB  - OBJECTIVE: To observe the effects of 2-deoxyglucose inhibiting synovial pannus of
      adjuvant arthritis rats and to explore its potential mechanism of inhibiting
      angiogenesis by investigating proliferation, migration and matrigel tube
      formation assay in vitro. METHODS: The effect of 2-DG on synovial pannus was
      evaluated by histopathology of HE staining; HUVEC proliferation was determined by
      CCK-8 method; migration of FLS were determined by transwell; In vitro matrigel
      tube formation assay was made for assessing tube number of HUVEC; p-AMPK and Bcl
      2 were detected by Western blot assay; AMPK signaling pathway in HUVEC was
      inhibited by compound C, which is an inhibitor of AMPK activation. RESULTS: 2-DG
      (200 mg/kg) obviously decreased appearance of synovial pannus (P < 0.01); in
      vitro, 2-DG (0.5 mmol/L and/or 5 mmol/L) obviously inhibited proliferation,
      migration and tube number of HUVEC (P < 0.01 or P < 0.001), and its effects on
      HUVEC were reversed by using AMPK antagonist (Compound C); Western blot showed
      that 2-DG (5 mmol/L) increased expression of p-AMPK and decreased expression of
      Bcl-2 (P < 0.05). CONCLUSIONS: Activating AMPK pathway and decreasing expression
      of Bcl-2 may the potential mechanism by which 2-DG contributes to anti
      angiogenesis and effects of inhibiting proliferation, migration and tube number
      of HUVEC.

PMID- 30187878
TI  - [10-gingerol inhibits proliferation of hepatocellular carcinoma HepG2 cells via
      Src/STAT3 signaling pathway].
AB  - OBJECTIVE: To study the inhibitory effect of 10-gingerol on the proliferation of
      hepatocellular carcinoma HepG2 cells and the role of Src/STAT3 signaling pathway
      in mediating the effect. METHODS: SYBYL-X2.1 software was used to simulate the
      interaction between 10-gingerol and Src. HepG2 cells treated with 10-gingerol at
      1, 3, 10 or MUol/L for 24 h were assessed for cell viability using MTT assay, and
      EdU staining was used to detect the cell proliferation and calculate the number
      of positive cells. The expressions of p-Src and p-STAT3 were detected using
      Western blotting, and the mRNA expressions of the target genes of STAT3 (cyclin
      D1 and CMCC) were detected using qPCR. RESULTS: 10-gingerol was capable of
      forming hydrogen bond with such Src residues as TRY-340, MET-341, MET-314, ASP
      404, and ILE-336. MTT assay showed that 10-gingerol at 3 and 10 MUmol/L
      significantly lowered the viability of HepG2 cells (P < 0.001). Treatment with 1,
      3, and 10 MUmol/L 10-gingerol significantly reduces the number of EdU-positive
      HepG 2 cells (P < 0.001). Western blotting showed that 10-gingerol at 3 and 10
      MUmol/L significantly decreased the phosphorylation levels of Src and STAT3 in
      HepG2 cells (P < 0.01). 10-gingerol at 1, 3, and 10 MUmol/L significantly
      decreased the mRNA expressions of cyclin D1 and CMCC as shown by qPCR (P < 0.01).
      CONCLUSIONS: 10-gingerol can dose-dependently inhibit the proliferation of HepG2
      cells and suppress the activation of Src and STAT3.

PMID- 30187879
TI  - [Progress in the applications of high-speed atomic force microscopy in cell
      biology].
AB  - Without losing its high resolution, high-speed atomic force microscope (HS-AFM)
      represents a perfect combinationof scanning speed and precision and allows real
      time and in situ observation of the dynamic processes in a biological system
      atboth the cellular and molecular levels. By combining the extremely high
      temporal resolution with the spatial resolution andcoupling with other advanced
      technologies, HS-AFM shows promising prospects for applications in life sciences
      such as cellbiology. In this review, we summarize the latest progress of HS-AFM
      in the field of cell biology, and discuss the impact ofenvironmental factors on
      conformation dynamics of DNA, the binding processes between DNA and protein, the
      domainchanges of membrane proteins, motility of myosin, and surface structure
      changes of living cells.

PMID- 30187880
TI  - [Quercetin attenuates Ox-LDL-induced calcification in vascular smooth muscle
      cells by regulating ROS-TLR4 signaling pathway].
AB  - OBJECTIVE: To determine whether quercetin inhibits oxidized low-density
      lipoprotein (Ox-LDL)-induced osteogenic differentiation and calcification of
      vascular smooth muscle cells (VSMCs) and understand the underlying mechanism.
      METHODS: The calcification of human VSMCs following Ox-LDL treatment was assessed
      using alizarin red staining and by detecting ALP activity. The mRNA expressions
      of the bone-related genes including Msx2, BMP2 and Osterix, and the contractile
      proteins including SMA and SM22a were analyzed using qPCR. The effects of
      quercetin were investigated on OxLDL-induced VSMC calcification and changes in
      ALP activity, expressions of Msx2, BMP2, Osterix, SMA and SM22a, ROS levels and
      SOD activity. The effect of Toll like receptor 4 (TLR4) silencing mediated by
      siRNA transfection on cell calcification, ALP activity, gene expressions and ROS
      levels were investigated. RESULTS: Ox-LDL treatment promoted VSMC calcification
      and up-regulated TLR4 expression. Quercetin treatment significantly attenuated Ox
      LDL-induced VSMC calcification, reduced ALP activity, down-regulated the
      expression levels of Msx2, BMP2 and Osterix, and up-regulated the expressions of
      vascular smooth muscle contractile proteins SMA and SM22a. In addition, Quercetin
      treatment markedly increased SOD activity, reduced ROS levels and TLR4 expression
      in VSMCs. Silencing TLR4 expression using TLR4 siRNA also significantly decreased
      calcification of the VSMCs. CONCLUSIONS: Quercetin inhibits Ox-LDL-induced VSMC
      calcification in VSMCs possibly by targeting the ROS/TLR4 signaling pathway.

PMID- 30187881
TI  - [Lipid-lowering effect of propolis in mice with Triton-WR1339-induced
      hyperlipidemia and its mechanism for regulating lipid metabolism].
AB  - OBJECTIVE: To evaluate the therapeutic effect of propolis against Triton-WR1339
      induced hyperlipidemia in mice and explore the underlying mechanism. METHODS:
      C57BL/6 mice were randomly divided into 7 groups (n=10), including the control
      group, hyperlipidemia model group, fenofibrate (30 mg/kg) treatment group, and 4
      treatment groups treated with low- (30 mg/kg) or high-dose (60 mg/kg) propolis
      HB01 or HB02. In all but the control group, acute hyperlipidemia models were
      established by intramuscular injection of Triton WR-1339, and corresponding
      treatments were administered via gastric lavage for 7 days. After the treatments,
      blood samples were collected for testing the levels of total cholesterol (TC),
      triglycerides (TG), highdensity lipoprotein-cholesterol (HDL-C), low-density
      lipoprotein-cholesterol (LDL-C), malondialdehyde (MDA), superoxide dismutase
      (SOD), alanine aminotransferase (GPT), and aspartate aminotransferase (GOT);
      Western blotting was used to detect the expressions of the proteins involved in
      lipid metabolism in the liver tissues including ABCA1, ABCG8, LDLR, and SR-B1.
      RESULTS: Compared with the normal control group, the mice with Triton-WR1339
      induced hyperlipidemia showed significantly increased levels of TC, TG, LDL, MDA,
      GPT, and GOT and lowered HDL-C levels and SOD activity (P < 0.05). Treatments
      with fenofibrate and the 2 propolis at either low or high dose significantly
      reversed Triton-WR1339-induced changes in blood lipids (P < 0.05), and the
      effects of propolis were more potent. Triton-WR1339 injection also significantly
      decreased the expressions levels of ABCA1, ABCG8, LDLR, and SR-B1 in the liver (P
      < 0.05), and these changes were obviously reversed by treatments with fenofibrate
      and propolis (P < 0.05), especially by the latter. CONCLUSIONS: The lipid
      lowering effects of propolis are mediated by improving lipid metabolism and
      regulating the expressions of lipid transport proteins in the liver tissue.

PMID- 30187882
TI  - [Monoside antagonizes triptolide-induced hepatocyte apoptosis via the anti
      oxidative stress pathway].
AB  - OBJECTIVE: To investigate the protective effect of monoside against triptolide
      induced liver injury and explore its molecular mechanism. METHODS: BALB/C mice
      treated with gastric lavage with triptolide and monoside, either alone or in
      combination, were examined for changes of hepatic biochemical parameters using
      the serological method. The growth inhibition rate of HepG2 cells treated with
      triptolide or monoside or both was assessed with MTT assay, and the cell
      morphological changes were observed using laser confocal microscopy; the
      expressions of the target proteins in the antioxidative stress pathway were
      detected using flow cytometry and Western blotting. RESULTS: In BALB/C mice,
      gastric lavage of triptolide induced obvious hepatic damage. In HepG2 cells,
      treatment with triptolide significantly inhibited the cell growth, resulting in a
      cell viability as low as 72.83% at 24 h; triptolide also induced obvious cell
      apoptosis and cell nucleus deformation, causing an apoptosis rate of 43.1% in the
      cells at 24 h. Triptolide significantly reduced the expressions of Nrf2 and HO-1
      proteins related with the oxidative stress pathway. Combined treatment with
      morroniside obviously reversed these changes, resulting in significantly
      decreased hepatic biochemical parameters and the liver index in BALB/C mice and
      in significantly lowered cell apoptosis rate, improved cell morphology, and
      increased Nrf2 and HO-1 protein expressions in HepG2 cells. CONCLUSIONS: Monoside
      protects against triptolide-induced liver injury possibly by relieving oxidative
      stress.

PMID- 30187883
TI  - [Long chain non-coding RNA MALAT-1 gene knockdown inhibits growth and migration
      and promotes apoptosis of human laryngeal squamous cell carcinoma Hep-2 cells in
      vitro].
AB  - OBJECTIVE: To investigate the effect of knocking down long chain non-coding RNA
      MALAT-1 gene on the biologicalbehaviors of human laryngeal squamous cell
      carcinoma Hep-2 cells. METHODS: With immortalized nasopharyngeal epithelial(NPE)
      cell line NP-69 as the reference, MALAT1 expression in FaDu, Hep-2 and
      nasopharyngeal carcinoma CNE-2Z cells weredetected using real-time PCR. Hep-2
      cells were transfected with shmalat1 lentivirus and the expression of MALAT1
      wasdetected. MTT assay, flow cytometry, Transwell assay and M Atrigel
      invasiveness test were used to evaluate the effect ofMALAT-1 knockdown on the
      proliferation, cell cycle, cell apoptosis, migration, and invasiveness of Hep-2
      cells. RESULTS: Compared with NP-69 cells, Hep-2 cells, FaDu cells, and CNE-2Z
      cells all showed significantly increased MALAT-1expression. In Hep-2 cells,
      knockdown of MALAT-1 significantly inhibited the cell proliferation, increased
      the cell percentagein S phase (P < 0.01), decreased the cell percentage in G2/M
      phase (P < 0.01), and attenuated the migration and invasiveness of thecells.
      CONCLUSIONS: MALAT-1 is over-expressed in laryngeal squamous cell carcinoma, and
      knocking down MALAT-1 gene cansignificantly suppress the proliferation, invasion
      and migration and promotes apoptosis of the cancer cells.

PMID- 30187884
TI  - [rotective effect of bone marrow mesenchymal stem cells-derived exosomes against
      testicular ischemia-reperfusion injury in rats].
AB  - OBJECTIVE: To investigate the protective effect of bone marrow mesenchymal stem
      cells (BMSCs)-derived exosomesagainst testicular ischemia-reperfusion injury
      (IRI) in rats. METHODS: Rat BMSCs were isolated, cultured and identified in
      theprimary culture. The exosomes were extracted from the BMSCs and characterized
      using nanoparticle tracking analysis, transmission electron microscopy, and
      Western blotting. Twenty-four healthy male SD rats were randomly divided into
      shamoperation group, testicular IRI with saline treatment group and IRI with
      exosome treatment group. The contralateral testes ofthe rats were collected for
      pathological observation, aseessment of superoxide dismutase (SOD) and
      malondialdehyde (MDA), and detection of HMGB1, caspases-3 and cleaved caspase-3
      expressions using Western blotting. RESULTS: We successfullyobtained exosomes
      from rat BMSCs. Testicular IRI significantly impaired testicular spermatogenesis,
      which was markedlyimproved by treatment with the exosomes (P < 0.05). Testicular
      IRI also caused significant increase in the protein expression ofHMGB1, caspase-3
      and cleaved caspase-3 in the testicular tissue, and treatment with the exosomes
      obviously amelioratedthese changes (P < 0.05). CONCLUSIONS: BMSCs-derived
      exosomes protects against testicular IRI due to the anti-oxidant,
      antiinflammatory and anti-apoptosis activities of the exosomes.

PMID- 30187885
TI  - Hematology Laboratory Survey

PMID- 30187886
TI  - Interleukin-2-330T/G and Interleukin-10-1082A/G Genetic Polymorphisms and B-Cell
      Non-Hodgkin Lymphoma

PMID- 30187888
TI  - PHLPP1 is a metastasis suppressor in melanoma.

PMID- 30187889
TI  - Phosphodiesterase-5 inhibitors for colon cancer chemoprevention.

PMID- 30187887
TI  - Comprehensive analysis of circRNA expression pattern and circRNA-miRNA-mRNA
      network in the pathogenesis of atherosclerosis in rabbits.
AB  - Atherosclerosis is a chronic and multifactorial inflammatory disease and is
      closely associated with cardiovascular and cerebrovascular diseases. circRNAs can
      act as competing endogenous RNAs to mRNAs and function in various diseases.
      However, there is little known about the function of circRNAs in atherosclerosis.
      In this study, three rabbits in the case group were fed a high-fat diet to induce
      atherosclerosis and another three rabbits were fed a normal diet. To explore the
      biological functions of circRNAs in atherosclerosis, we analyzed the circRNA,
      miRNA and mRNA expression profiles using RNA-seq. Many miRNAs, mRNAs and circRNAs
      were identified as significantly changed in atherosclerosis. We next predicted
      miRNA-target interactions with the miRanda tool and constructed a differentially
      expressed circRNA-miRNA-mRNA triple network. A gene ontology enrichment analysis
      showed that genes in the network were involved in cell adhesion, cell activation
      and the immune response. Furthermore, we generated a dysregulated circRNA-related
      ceRNAs network and found seven circRNAs (ocu-cirR-novel-18038, -18298, -15993, 
      17934, -17879, -18036 and -14389) were related to atherosclerosis. We found these
      circRNAs also functioned in cell adhesion, cell activation and the immune
      response. These results show that the crosstalk between circRNAs and their
      competing mRNAs might play crucial roles in the development of atherosclerosis.

PMID- 30187890
TI  - Formation and stability of water clusters at the molybdenum disulfide interface:
      a molecular dynamics simulation investigation.
AB  - In this work structural properties and dynamic behavior of a water nano droplet
      on the molybdenum disulfide were considered. The simulation results show that
      water molecules form polygon clusters on the interface, and most of which are
      hexagonal. Structures of water clusters at the interface are seen in two forms of
      curved and flattened polygons, which result in the formation of hydrogen bonds
      between and in the adjacent layers, respectively. Most of the clusters have
      circular flattened structures. Calculations of the lifetime of hydrogen bonds of
      water molecules at the interface also show that hydrogen bonds between water
      molecules at the interface have a low stability. This leads to the permanent
      formation and breaking down of hydrogen bonds of water molecules which can cause
      movement of water molecules and, consequently, the displacement of the center of
      mass and droplet motion. Considering the changes in the center of mass of a water
      droplet at the MoS2 interface display, the water droplet has a significant
      spontaneous motion.

PMID- 30187892
TI  - An SVM approach for identifying atrial fibrillation.
AB  - OBJECTIVES: We designed an automated algorithm to classify short
      electrocardiogram (ECG) strips into four categories: normal rhythm, atrial
      fibrillation, noisy segment, or other rhythm disturbances. APPROACH: The
      algorithm is based on identification of the R peak and recognition of the other
      ECG waves. Time-frequency domain features, the average and variability of the
      intra-beat temporal interval, and the average beat morphology were also
      calculated. These features (61 features at all) were the input to a support
      vector machine (SVM) with and without a feed-forward 2-layer neural network
      consisting of 20 neurons trained on an annotated database. Data were drawn from
      the PhysioNet Challenge 2017 dataset, consisting of 8528 recordings, of which
      60.43% are normal, 0.54% are noisy, 9.04% are AF, and 30% are other rhythm
      disturbances. The results were validated on 3658 ECG recordings of similar length
      and percent from each of the four groups. MAIN RESULTS: We used a quadratic SVM
      classifier with a combination of 61 features to classify the short ECG recordings
      into one of the four categories mentioned above. The use of an additional neural
      network to improve the identification of 'other' rhythms that were misclassified
      as 'normal' did not statistically affect the results. Our algorithm obtained a
      total score (F1) of 0.80 on the hidden dataset (placing 18th-24th out of all the
      algorithms participating in the challenge; places 18-24 received the same score).
      SIGNIFICANCE: Our algorithm was also able to classify AF versus non-AF and normal
      versus abnormal (arrhythmia or noise) records.

PMID- 30187891
TI  - The relation between local structural distortion and the low-temperature magnetic
      anomaly in Fe7S8.
AB  - Structural defects on an atomic level can crucially impact the magnetic
      properties of a material. We study this phenomenon by means of magnetometry and
      powder neutron diffraction on a stoichiometric, monoclinic pyrrhotite (Fe7S8),
      which is a classic omission structure with a magnetic anomaly at about 30 K. The
      initial structural distortion of the pyrrhotite at 300 K caused by the vacancy
      arrangement decreases upon cooling, and simultaneous to the magnetic anomaly the
      anisotropic contraction of the unit cell homogenizes the covalency of the Fe-Fe
      bonds with lengths less than 3.0 A and the Fe-S-Fe bond angles. These changes on
      the atomic level affect the spin-orbit coupling and the super-exchange
      interactions in Fe7S8, and trigger the low-temperature magnetic anomaly within a
      crystallographically stable system.

PMID- 30187893
TI  - Effect of toe joint stiffness and toe shape on walking biomechanics.
AB  - During typical human walking, the metatarsophalangeal joints undergo
      extension/flexion, which we term toe joint articulation. This toe joint
      articulation impacts locomotor performance, as evidenced by prior studies on
      prostheses, footwear, sports and humanoid robots. However, a knowledge gap exists
      in our understanding of how individual toe properties (e.g. shape, joint
      stiffness) affect bipedal locomotion. To address this gap, we designed and built
      a pair of adjustable foot prostheses that enabled us to independently vary
      different toe properties, across a broad range of physiological and non
      physiological values. We then characterized the effects of varying toe joint
      stiffness across a range of different ankle joint stiffness conditions, and the
      effects of varying toe shape on walking biomechanics. Ten able-bodied individuals
      walked on a treadmill with prostheses mounted bilaterally underneath simulator
      boots (which immobilized their biological ankles). We collected motion capture
      and ground reaction force data, then computed joint kinematics and kinetics, and
      center-of-mass (COM) power and work. To our surprise, we found that varying toe
      joint stiffness affected COM Push-off dynamics during walking as much as, or in
      some cases even more than, varying ankle joint stiffness. Increasing toe joint
      stiffness increased COM Push-off work by up to 48% (6 J), and prosthetic
      anklefoot Push-off work by up to 181% (12 J). In contrast, large changes in toe
      shape had little effect on gait. This study brings attention to the toes, an
      aspect of prosthetic and robotic foot design that is often overlooked or
      overshadowed by design of the ankle. Optimizing toe joint stiffness in assistive
      and robotic devices (e.g. prostheses, exoskeletons, robot feet) may provide a
      complementary means of enhancing Push-off or other aspects of locomotor
      performance, in conjunction with the more conventional approach of augmenting
      ankle dynamics. Future studies are needed to isolate the effects of additional
      toe properties (e.g. toe length).

PMID- 30187894
TI  - Detection of atrial fibrillation from ECG recordings using decision tree ensemble
      with multi-level features.
AB  - OBJECTIVE: Detecting atrial fibrillation (AF) from electrocardiogram (ECG)
      recordings remains a challenging task. In this paper, a new AF detection method
      was proposed to classify the ECG recordings into one of four classes: Normal
      rhythm, AF, Other rhythm, and Noisy recordings. APPROACH: The proposed method
      comprised preprocessing, feature extraction, and classification. In
      preprocessing, R-peaks were detected, and RR intervals and delta RR intervals
      were extracted. In feature extraction, 30 multi-level features were extracted,
      including AF features (n  =  4), morphology features (n  =  20), RR interval
      features (n  =  2), and features of similarity index between beats (n  =  4). In
      classification, these features were used to train an AdaBoosted decision tree
      ensemble for classifying ECG recordings into the four classes. The decision tree
      ensemble was trained with 100-fold cross-validation on the training dataset (n  =
      8528) provided by the 2017 PhysioNet/Computing in Cardiology (CinC) Challenge.
      MAIN RESULTS: The trained classifier was submitted to the Challenge for testing
      on the unavailable test dataset (n  =  3658); the official F 1 scores for
      'Normal', 'AF', 'Other' were 0.91, 0.82, and 0.73, respectively, and the overall
      F 1 score was 0.82 (ranking equal 5th with eight other algorithms in the 2017
      PhysioNet/CinC Challenge). SIGNIFICANCE: The proposed algorithm may be used as a
      new method for AF detection.

PMID- 30187895
TI  - Cognitive Impairment Due to Leptin Withdrawal in Rat Offspring of Dams with
      Maternal Diet-Induced Obesity.
AB  - BACKGROUND Obesity during pregnancy is a potential threat to the health and
      neurodevelopment of the offspring. This study investigated the effect of maternal
      diet-induced obesity (DIO) on the cognitive abilities of the offspring in rats.
      MATERIAL AND METHODS Female Sprague-Dawley rats were fed a high-fat diet to
      induce obesity, and the leptin levels in dams and offspring were evaluated using
      ELISA. The effect of DIO on the learning and memory in offspring was measured
      using electrophysiology and the Morris water maze test. In addition, the
      expression of molecules related to synaptic plasticity was investigated.
      Furthermore, the effect of leptin on neuronal cells was investigated, and the
      influence of leptin on the regulation of calcium current activity was evaluated
      in vitro. RESULTS Results showed that DIO dams had increased leptin levels during
      gestation, and offspring had drastically decreased leptin levels after delivery.
      The cognitive ability of offspring with maternal DIO was mildly impaired after
      delivery. Furthermore, long-term potentiation in DIO neonatal offspring was lower
      than in the control group at 2-3 weeks old; decreased expression of the leptin
      receptor was accompanied by N-methyl-D-aspartate receptor (NMDAR) downregulation
      during neonatal development. In addition, it was demonstrated that leptin
      enhanced NMDAR activity and promoted calcium current activity in a concentration
      dependent manner. CONCLUSIONS The results indicated that the neonatal offspring
      of DIO dams showed cognitive impairment during neonatal development, which may be
      attributed to leptin withdrawal.

PMID- 30187896
TI  - Volatile oil from alpinia officinarum promotes lung cancer regression in vitro
      and in vivo.
AB  - The anti-lung cancer activity of volatile oil from Alpinia officinarum (VOAO) and
      the underlying mechanism has not been studied. Herein, VOAO was extracted by
      steam distillation and its components were identified by GC-MS analysis. Cells
      viability was measured by an MTT assay and the cell survival capacity was tested
      via a colony formation assay. Apoptosis cells were detected using the Annexin V
      FITC/PI method. Hoechst 33342 cell unclear staining was employed to evaluate the
      nuclear morphology change. The mitochondrial membrane potential was detected by a
      JC-1 staining assay. Bcl-2, Mcl-1 and cleaved caspase-3 proteins were quantified
      by immune blotting. Furthermore, VOAO anti-cancer activity was evaluated on an
      A549 cell xenograft nude mice model. Our results have revealed that VOAO could
      inhibit the cell viability of lung carcinoma cells and the colony formation
      capacity. VOAO downregulates Bcl-2 and Mcl-1 and triggers dysfunction of the
      mitochondrial membrane potential. VOAO further activates caspase-3 cleavage and
      induces lung cancer cells apoptosis. In addition, VOAO administration
      significantly suppresses lung cancer growth in xenograft mice without obvious
      hepatotoxicity. We conclude that VOAO could be an effective, low cytotoxicity
      natural component for treatment of lung carcinoma.

PMID- 30187897
TI  - Effects of different levels of methionine on sow health and plasma metabolomics
      during late gestation.
AB  - Fetal growth, survival, and development are benchmarks for the production
      performance of sows, and methionine has been shown to impact fetal protein mass
      and the transport of nutrients through the uteroplacental vasculature. This study
      evaluated the effects of dietary methionine, administered during the late
      gestation period, on the production performance of sows. Specifically, it
      measured the effect of methionine on biochemical indicators in the plasma, plasma
      metabolites, and fecal bacterial communities. Thirty Landrace * Large White sows
      at day 90 of gestation were randomly assigned to three groups and fed the
      following diets: (1) a basal diet containing 0.36% methionine; (2) a basal diet +
      0.12% methionine (0.48% methionine); and (3) a basal diet + 0.24% methionine
      (0.60% methionine). The results showed that the 0.48% methionine diet
      significantly (P < 0.05) increased piglets' birth weight, and the 0.60%
      methionine diet significantly (P < 0.05) improved the survival ratio. Dietary
      methionine lowered the triglyceride (TG) levels (P < 0.05), total bilirubin
      (BILT3) (P < 0.001) concentration, and gamma-glutamyl transferase (GGT) (P <
      0.05) enzyme activity in the plasma at farrowing. In the plasma metabolomics,
      dietary methionine increased plasma pyroglutamic acid and decreased 2
      pyrrolidinone, hypotaurine, and anyl-histidine in both the 0.48% methionine and
      0.60% methionine groups. In addition, the bacteria richness (Chao1 and ACE) and
      diversity (Shannon) were reduced in the 0.48% methionine group. For the
      microbiota composition, at the family level, the 0.48% methionine group had a
      significant increase (P < 0.05) in the relative abundance of Methanobacteriaceae
      compared to the other two groups, but a decrease in the relative abundance of
      Enterobacteriaceae, Ruminococcaceae and Erysipelotrichaceae compared to the 0.60%
      methionine group. In conclusion, a diet consisting of 0.48% methionine
      administered during the late gestation period can improve the production
      performance of sows and maintain their health.

PMID- 30187902
TI  - Luminescent liquid crystalline hybrid materials by embedding octahedral
      molybdenum cluster anions with soft organic shells derived from tribenzo[18]crown
      6.
AB  - Crown ethers and their derivatives are versatile building blocks for the design
      of supramolecular materials. They can be functionalized at will and are well
      known for their abilities to complex with alkali cations. Here, we show that
      emissive lanthanide free hybrid materials can be generated by using such building
      blocks. The organic tribenzo[18]crown-6 central core was functionalized via six
      fold Suzuki cross-coupling as a key reaction with three o-terphenyl units which
      could be converted into their corresponding triphenylenes by the Scholl reaction,
      leading to novel liquid-crystalline columnar materials. Selected
      tribenzo[18]crown-6 o-terphenyls could interact with emissive ternary metal
      cluster compound salts to generate hybrid materials combining the properties of
      both moieties. Due to synergistic effects and despite the anisometry of the
      cluster compounds, individual properties such as liquid-crystalline phase
      stability of the organic part and emission abilities of its inorganic counter
      part are enhanced in the hybrid compounds.

PMID- 30187904
TI  - An integrated metabolomic strategy for the characterization of the effects of
      Chinese yam and its three active components on septic cardiomyopathy.
AB  - Chinese yam (CY), used as both a traditional Chinese medicine and a nutritious
      food, is an excellent candidate for treating septic cardiomyopathy (SCM).
      Adenosine, arbutin and allantoin are the major active components in the aqueous
      extract of CY. The aim of the present study was to interpret the roles of CY,
      adenosine, arbutin and allantoin in SCM treatment. Firstly, significant
      physiological indexes were examined to assess the model and treatment effects of
      CY, adenosine, arbutin and allantoin. Then, a metabolomic approach was utilized
      to reveal the metabolic disorders in SCM concerning the intervention of
      CY/adenosine/arbutin/allantoin. The integrated results demonstrated that
      adenosine, arbutin and allantoin are responsible for the efficacy of CY on SCM
      treatment by regulating amino acid, arachidonic acid, sphingolipid,
      glycerophospholipid and glycol metabolism. Moreover, adenosine and/or arbutin
      could be used as a substitute for CY in treating SCM, and allantoin efficacy was
      slightly weaker. This integrated metabolomic approach performed excellently in
      understanding the herbal function and the roles of its components.

PMID- 30187905
TI  - Human leukocyte antigens in cancer metastasis: Prognostic approach and
      therapeutic susceptibility.
AB  - Human leukocyte antigens (HLA), which are a group of antigen-presenting proteins,
      are classified into two main groups: classic (including HLA-I, HLA-II, HLA-III)
      and non-classic. These molecules are expressed on the surface of several immune
      cells, which contribute to the defense of body against foreign antigens. Changing
      expressions of these molecules on tumor cells can be related to reduced ability
      of the immune system in killing tumor cells, as well as metastasis induction of
      many solid tumors. The purpose of this review article is to assess the possible
      relationship between changing expressions of HLA molecules with cancer metastasis
      and relapse. It can be stated that the changes in the expressions of HLA
      molecules on tumor cells are an important mechanism for tumor cell escape from
      immune cells. Therefore, these changes can be associated with tumor development,
      metastasis, or relapse. Given the essential role of HLA molecule expression in
      cancer metastasis and relapse, identification of prognostic value of these
      alterations as well as targeting HLA molecules with new therapeutic approaches
      may lead to the prevention of these complications.

PMID- 30187907
TI  - Immunohistochemical analysis of spinal cord components in mouse model of
      experimental autoimmune encephalomyelitis.
AB  - INTRODUCTION: Experimental autoimmune encephalomyelitis (EAE) is a widely used
      animal model for studying immunopathology of multiple sclerosis (MS) because it
      repeats the hallmarks of the human disease, such as focal inflammation and
      demyelination of the central nervous system, subsequently leading to axonal and
      neuronal loss. The interrelationships, timing and sequence of different
      pathological processes that lead to histologically observed lesions in SM are
      still incompletely understood. MATERIAL AND METHODS: EAE was induced in female
      C57Bl/6 mice by active immunization with MOG35-55 antigen. Development of the
      neurological symptoms in the animals was monitored and on that basis spinal cords
      were collected in three successive phases of the disease (onset, peak, chronic).
      Total leukocytes, T cells, macrophages/microglia, oligodendrocytes, damaged axons
      and surviving neuronal cell bodies were visualized using appropriate
      immunohistochemical markers and their density was quantitatively assessed using
      image analysis software. RESULTS: The density of all studied cells except neurons
      was significantly higher in EAE mice than in the control mice. The density of
      total leukocytes, T cells, and damaged axons increased from the onset to the peak
      phase and decreased in the chronic phase to reach values lower than those in the
      peak phase. The density of macrophages/microglia increased in the peak phase and
      remained at the elevated level in the chronic phase. Oligodendrocytes showed the
      highest density in the onset phase and gradually decreased afterwards. The
      density of neuronal cell bodies decreased only in the chronic phase of the
      disease. CONCLUSIONS: In mouse model of EAE, inflammatory cells predominate in
      the early phases of the disease. This study shows for the first time that
      inflammation precedes oligodendrocyte death and neuronal loss and that
      macrophages/ microglia are the only cells persisting in large numbers in the
      chronic phase of the disease, probably because of the switch from proinflammatory
      to anti-inflammatory phenotype.

PMID- 30187906
TI  - Matrix metalloproteinases-2, -7 and tissue metalloproteinase inhibitor-1
      expression in human endometrium.
AB  - INTRODUCTION: Endometrium undergoes regular, cyclic tissue remodeling mostly
      associated to the endocrine system status. It is well-known fact that steroid
      hormones are strongly responsible for changes in endometrium. The precise
      mechanism of their action is still under investigation. The aim of the study was
      to evaluate the expression of metalloproteinases 2 and 7 (MMP-2, -7) and tissue
      inhibitor of metalloproteinase 1 (TIMP-1) in human endometrium in relation to
      serum concentrations of estradiol and progesterone during different phases of
      menstrual cycle. MATERIAL AND METHODS: The study material consisted of 52 biopsy
      samples; 12 obtained in the proliferative phase, 11 in the secretory phase and 29
      during menstruation. Expression of MMP-2, MMP-7 and TIMP-1 was assessed by
      immunohistochemistry. Serum concentrations of estradiol and progesterone at time
      of biopsy were evaluated by immunochemistry assay. Results of the study were
      statistically assessed by linear regression model. RESULTS: Increased serum
      concentration of estradiol was associated with increased MMP-2 expression in
      proliferative phase but decreased in secretory phase and during menstruation. No
      significant relationship was found between progesterone concentration and MMP-2
      expression. Moreover, no difference in the expression of MMP-7 and TIMP-1 in the
      endometrium in relation to hormone levels and menstrual cycle phases were
      observed. CONCLUSIONS: The results of the study indicate that estradiol influence
      MMP-2 expression in the endometrium depends on the phase of menstrual cycle. Such
      relationships were not found for MMP-7 and TIMP-1 and further tests clarifying
      association between estradiol and MMPs are needed.

PMID- 30187908
TI  - Expression of peroxiredoxins in the human testis, epididymis and spermatozoa and
      their role in preventing H2O2-induced damage to spermatozoa.
AB  - INTRODUCTION: High levels of reactive oxygen species (ROS) have potential toxic
      effects on testicular function and sperm quality. Peroxiredoxins (PRDXs) are
      enzymes with a role as ROS scavenger. The aim of the study was to reveal the
      presence and localization of PRDXs in human testis, epididymis and spermatozoa,
      and the protective roles of PRDX2 and PRDX6 in sperm motility. MATERIAL AND
      METHODS: The presence and localization of PRDXs in the human testis, epididymis
      and spermatozoa were detected by immunohistochemistry, western blot and
      immunofluorescence. The effect of anti-peroxidative damage to spermatozoa was
      examined by adding H2O2 to the recombinant protein-treated spermatozoa. RESULTS:
      There were strong signals of PRDX1 in spermatogonia and round spermatids; PRDX2
      in the round spermatids; PRDX4 and 5 in spermatogonia; PRDX6 in Sertoli cells.
      PRDXs were also found in epididymal epithelial cells where the expression of
      PRDX1, 4, 5, 6 in the cauda was higher than in the caput of epididymis. PRDX1-6
      immunoreactivity was found throughout acrosome, post-acrosomal region, equatorial
      segment, neck and cytoplasmic droplet, midpiece and principal piece. The H2O2
      induced reduction in sperm motility was reversed by recombinant PRDX2 or PRDX6 in
      a dose-dependent manner. CONCLUSIONS: PRDX1-6 in the human testis and epididymis
      presented cell-specificity. PRDX2 and 6 are potential antioxidant protectors for
      human spermatozoa.

PMID- 30187909
TI  - Population density and developmental stress in the Neolithic: A diachronic study
      of dental fluctuating asymmetry at Catalhoyuk (Turkey, 7,100-5,950 BC).
AB  - OBJECTIVES: The transition from foraging to farming is usually associated with
      unprecedented population densities coupled with an increase in fertility and
      population growth. However, little is known about the biological effects of such
      demographic changes during the Neolithic. In the present work, we test the
      relationship between diachronic changes in population size, relative exposure to
      developmental stressors, and patterns of dental fluctuating asymmetry in the
      Neolithic population of Catalhoyuk (Turkey, 7,100-5,950 cal BC). MATERIALS AND
      METHODS: We calculate fluctuating asymmetry of mesio-distal and bucco-lingual
      diameters of upper and lower permanent canines and first and second molars on a
      large (N = 259) sample representing adults of both sexes and various age classes.
      RESULTS: Results show only a moderate decrease of fluctuating asymmetry during
      the late phase of occupation of the site, possibly linked to a decrease in
      population density, and no differences in asymmetry between sexes. DISCUSSION:
      Though preliminary, our data reflect the presence of developmental stressors
      throughout the occupation of the site, albeit with a slight improvement in living
      conditions during the latest periods of occupation. At the same time, these data
      confirm the key role of diet as buffer against the detrimental effects of
      fluctuating demographic pressures on the biology of prehistoric human
      populations.

PMID- 30187910
TI  - Gendered Packaging of a STEM Toy Influences Children's Play, Mechanical Learning,
      and Mothers' Play Guidance.
AB  - To study effects of the gender-packaging of science, technology, engineering, and
      mathematics (STEM) toys, mother-child dyads (31 daughters; 30 sons; M = 5.2
      years) were randomly assigned to play with a mechanical toy packaged for girls
      (GoldieBlox) or boys (BobbyBlox). When familiarizing themselves with the toy to
      prepare for play, mothers given BobbyBlox built more with toy pieces than did
      mothers given GoldieBlox. During dyadic play, mothers with sons built more;
      mothers with daughters read the toy's narrative instructions more. Children's
      independent play likewise varied with game packaging. Girls learned the
      mechanical belt-drive principle better from playing with BobbyBlox; boys learned
      the principle better from playing with GoldieBlox. Implications for gender-schema
      theories, STEM interventions, and toy marketing are discussed.

PMID- 30187911
TI  - Cardiac Disease in Elderly Holocaust Survivors Who Live in Israel: A Case for
      Risk and Resilience.

PMID- 30187912
TI  - Perioperative cardiovascular complications following urogynecological operations.
AB  - INTRODUCTION: The risk of perioperative cardiovascular complications following
      operations for urinary incontinence and pelvic organ prolapse (POP) must be taken
      into consideration during surgical planning. The literature on the cardiovascular
      risk following urinary incontinence and POP operations shows conflicting results.
      Our aims were to provide an estimate of the mortality and the risk of
      cardiovascular complications following urinary incontinence and POP operations
      considering women's preoperative cardiovascular comorbidity. MATERIAL AND
      METHODS: This nationwide register-based study includes a total of 13 992
      operations for urinary incontinence and 35 765 for POP from 2007 to 2017. The
      risk was estimated as an incidence/rate ratio for women with and without former
      cardiovascular comorbidity adjusted for relevant confounders by using a case
      crossover study design. RESULTS: A total of 7677 patients were at high risk, with
      a cardiovascular comorbidity prior to the operation, and 42 076 patients were at
      low risk, with no cardiovascular comorbidity. Overall, 11 patients died within 30
      days following an operation, of whom five were in the high-risk group and six in
      the low-risk group. Of the women at high risk, 0.59% had cardiovascular
      complications from 0 to 6 days following an operation, corresponding to an
      incidence/rate ratio of 3.64 (95% CI; 2.67-4.97), compared with women at low risk
      where no complications were registered in the first week. CONCLUSIONS: We found
      an increased risk of cardiovascular complications following urogynecological
      operations in women with preoperative cardiovascular comorbidity, and no
      increased risk in women without prior cardiovascular comorbidity. In general, the
      risk of cardiovascular complications was lower than that found in previous
      studies.

PMID- 30187913
TI  - Health-related quality of life after post-haemorrhagic hydrocephalus in children
      born preterm.
AB  - AIM: To determine the health-related quality of life (HRQoL) of children born
      preterm (gestational age <32wks) after post-haemorrhagic hydrocephalus requiring
      shunt (PHH-S), and to examine the impact of perinatal and neurological morbidity
      on their QoL. METHOD: Forty infants (18 females, 22 males; aged 2y 2mo-8y 4.5mo)
      born preterm with PHH-S were matched for gestational age, birthweight, and sex
      with infants born preterm with normal cranial ultrasonography. Pediatric QoL
      Inventory parent-proxy report was administered at a mean age of 5 years 8 months.
      RESULTS: Children with PHH-S exhibited significantly lower mean HRQoL compared
      with controls in motor (36 [SD 34.9] vs 96.2 [SD 6.6]), emotional (59.8 [SD 26.7]
      vs 80.6 [SD 18.8]), social (55.6 [SD 29.7] vs 89.6 [SD 16.6]), and school (40.5
      [SD 22.9] vs 89.7 [SD 15.2]) domains (p<0.001). Multivariate regression
      incorporating neonatal risk factors revealed an independent effect of parenchymal
      brain involvement (beta=-0.6, p<0.01) and neonatal seizures (beta=-0.2, p<0.02)
      on total HRQoL. Low HRQoL of children with PHH-S was associated with
      neurodevelopmental morbidities: cerebral palsy (CP), epilepsy, vision and feeding
      problems, low cognitive, personal-social, and adaptive scores (p<0.05).
      Multivariate analysis indicated an independent contribution from severe CP (beta=
      0.4, p<0.001) and low personal-social score (beta=0.5, p<0.001). INTERPRETATION:
      Children born preterm after PHH-S exhibit significantly lower HRQoL scores
      compared with preterm born peers. HRQoL is associated with neonatal cerebral
      complications and neurodevelopmental morbidities. WHAT THIS PAPER ADDS: Children
      born preterm, after post-haemorrhagic hydrocephalus requiring shunt, have low
      health-related quality of life (HRQoL). A low HRQoL is associated with
      parenchymal brain involvement and with neurological morbidity. Severe cerebral
      palsy and low personal-social developmental scores have independent contributions
      to HRQoL.

PMID- 30187915
TI  - Pemphigus foliaceus induced by topical imiquimod treatment.

PMID- 30187914
TI  - Cerebral palsy trends in Australia (1995-2009): a population-based observational
      study.
AB  - AIM: To investigate trends in birth prevalence of cerebral palsy (CP) overall and
      by gestational age, and examine the distribution of motor type, spastic
      topography, and severity using Australian CP Register data from 1995 to 2009.
      METHOD: Prenatal and perinatal CP data were collated from state/territory CP
      registers. Birth prevalence estimates per 1000 live births and per 1000 neonatal
      survivors (NNS) were calculated in five epochs. Data from three state registers
      with population-level ascertainment were used to investigate birth prevalence
      trends by gestational age using Poisson regression. Distribution of motor type,
      spastic topography, and moderate to severe disability (IQ<=50 and/or Gross Motor
      Function Classification System levels III-V) were evaluated within birthweight
      categories. RESULTS: Birth prevalence of CP varied across population-level states
      but within each state declined significantly over time (p<0.05). Birth prevalence
      per 1000 neonatal survivors declined amongst children born before 28 weeks (South
      Australia, Victoria p<0.001) and those born at or after 37 weeks (Victoria
      p<0.001, Western Australia p<0.002). Across Australia the percentage of children
      with bilateral spastic CP declined amongst those born less than 1000g. The
      percentage of children with moderate to severe disability decreased (48%-34%,
      p<0.001). INTERPRETATION: Birth prevalence of CP declined. Encouragingly, the
      percentage of children with CP whose disability was moderate to severe also
      decreased. WHAT THIS PAPER ADDS: Birth prevalence of cerebral palsy (CP) differed
      but declined across Australian states (1995-2009). Australian CP birth prevalence
      declined significantly amongst children born before 28 weeks and those born at or
      after 37 weeks. The percentage of children with moderate to severe disability
      decreased.

PMID- 30187916
TI  - Correlation of clinical and pathologic evaluation of scarring alopecia.
AB  - BACKGROUND: Differentiating scarring and nonscarring alopecia poses a diagnostic
      dilemma for clinicians, with histopathology used to distinguish. The extent to
      which dermatologists are able to clinically classify alopecia has not been
      evaluated. METHODS: A retrospective study of pathology reports on 458 patients
      was used to calculate a kappa coefficient to correlate clinical presence of
      scarring or nonscarring alopecia to histopathologic presence of scarring or
      nonscarring. A multivariate analysis was performed to assess for associations
      with scarring. RESULTS: The kappa correlation coefficient was 0.59 (P < 0.0001),
      indicating moderate agreement and varied by race and sex. There were 15 times
      higher odds of making the clinical diagnosis of scarring alopecia (OR 14.64 95%
      CI [8.64-24.18]; P < 0.001), and this increased with age. CONCLUSIONS: These
      results suggest that clinical exam is moderately reliable in distinguishing
      between scarring and nonscarring alopecia. Our results highlight the need for
      education and diagnostic schemata for evaluation of alopecia based on gender and
      in skin of color.

PMID- 30187917
TI  - Are there missed opportunities for occupational therapy for people with dementia?
      An audit of practice in Australia.
AB  - BACKGROUND/AIM: Randomised trials have demonstrated that occupational therapy can
      delay functional decline, improve quality of life and increase leisure
      participation in people with dementia. However, surveys conducted with
      occupational therapists suggest that clinical practice does not reflect the type
      of intervention shown to be effective in research studies. Case note audits can
      be used to quantify practice and demonstrate how and where provision of care
      could improve without the potential bias associated with self-report. METHOD: A
      total of 87 occupational therapy case notes were audited from different service
      contexts in two states in Australia. The case notes were reviewed against
      criteria including duration of service, assessments conducted and interventions
      used. Descriptive statistics were used to present the data and examine
      associations between intervention, age of the person with dementia and whether or
      not the person lived alone. RESULTS: Services tended to be short-term with an
      average of 2.1 consultations per referral. The most common assessments related to
      home safety, falls risk and function. Intervention most commonly focussed on
      referrals to other services, environmental modification advice and assistive
      device prescription. CONCLUSION: This audit reveals that current occupational
      therapy practice for people with dementia focusses on assessment and management
      of risk and is usually limited to a couple of consultations. Future work should
      seek to evaluate if such approaches to care are effective for people with
      dementia.

PMID- 30187918
TI  - Plasma Phytosterol Half-Life and Levels Are Increased in Very Low Birth Weight
      Preterm Infants with Parenteral Nutrition-Associated Cholestasis.
AB  - Parenteral nutrition-associated cholestasis (PNAC) has been linked to plasma
      accumulation of phytosterols in infants receiving vegetable-oil-based lipid
      emulsions (LE). To date, information on the ability of infants with PNAC to
      metabolize intravenous (IV) phytosterols has been very limited. We characterized
      plasma phytosterol half-life in very low birth weight (VLBW) preterm infants with
      PNAC. As part of a prospective cohort study, VLBW infants with PNAC underwent
      serial blood sample measurements of sitosterol (Sito), campesterol (Camp), and
      stigmasterol (Stigma). Infants without PNAC served as controls (CTRL, control
      infants). Thirty-seven PNAC infants and 14 CTRL were studied. On PN day 7 and PN
      day 14, PNAC infants had higher plasma phytosterol concentrations compared to
      those of CTRL (p < 0.05). A significant and positive correlation was found
      between plasma Camp, Stigma, Sito concentrations, and IV phytosterol intake from
      birth to PN day 7 (p = 0.001, p = 0.001, and p = 0.005, respectively). Stigma
      concentration was positively correlated with conjugated bilirubin on PN day 7 (p
      = 0.012). After stopping IV LE, half-lives of Camp, Stigma, and Sito became
      significantly longer in PNAC infants than in CTRL (Camp: 18.8 +/-6.2 vs 11.8 +/
      3.0 days, p = 0.001; Stigma: 13.8 +/-5.8 vs 9.4 +/-3.4 days, p = 0.023; Sito:
      15.3 +/-5.0 vs 9.8 +/-3.0 days, p = 0.002). In conclusion, phytosterols increased
      earlier during PN and were eliminated slowly after stopping IV LE in PNAC infants
      than in CTRL. The Stigma concentration on PN day 7 could represent an early
      marker of cholestasis. Our results provide additional evidence on the
      relationship between IV phytosterols and PNAC.

PMID- 30187919
TI  - Seizure susceptibility and infraslow modulatory activity in the intracranial
      electroencephalogram.
AB  - OBJECTIVE: Studies of infraslow amplitude modulations (<0.15 Hz) of band power
      time series suggest that these envelope correlations may form a basis for distant
      spatial coupling in the brain. In this study, we sought to determine how
      infraslow relationships are affected by antiepileptic drug (AED) taper, time of
      day, and seizure. METHODS: We studied intracranial electroencephalographic
      (icEEG) data collected from 13 medically refractory adult epilepsy patients who
      underwent monitoring at Yale-New Haven Hospital. We estimated the magnitude
      squared coherence (MSC) at <0.15 Hz of traditional EEG frequency band power time
      series for all electrode contact pairs to quantify infraslow envelope
      correlations between them. We studied, first, hour-long background icEEG epochs
      before and after AED taper to understand the effect of taper. Second, we analyzed
      the entire record for each patient to study the effect of time of day. Finally,
      for each patient, we reviewed the clinical record to find all seizures that were
      at least 6 hours removed from other seizures and analyzed infraslow envelope MSC
      before and after them. RESULTS: Infraslow envelope MSC increased slightly, but
      significantly, after AED taper, and increased on average during the night and
      decreased during the day. It was also increased significantly in all frequency
      bands up to 3 hours preseizure and 1 hour postseizure as compared to background
      icEEG (61 seizures studied). These changes occurred for both daytime and
      nighttime seizures (28 daytime, 33 nighttime). Interestingly, there was
      significant spatial variability to these changes, with the seizure onset area
      peaking at 3 hours preseizure, then showing progressive desynchronization from 3
      hours preseizure to 1 hour postseizure. SIGNIFICANCE: Infraslow envelope analysis
      may be used to understand long-term changes over the course of icEEG monitoring,
      provide unique insight into interictal electrophysiological changes related to
      ictogenesis, and contribute to the development of novel seizure forecasting
      algorithms.

PMID- 30187921
TI  - Effect of continuous intrathecal baclofen therapy in children: a systematic
      review.
AB  - AIM: To investigate the effects of continuous intrathecal baclofen (ITB) therapy
      in children with cerebral palsy (CP) and other neurological conditions. METHOD:
      This systematic review was conducted using standardized methodology, searching
      four electronic databases (PubMed, Embase, CINAHL, Cochrane Library) for relevant
      literature published between inception and September 2017. Included studies
      involved continuous ITB as an intervention and outcome measures relating to all
      International Classification of Functioning, Disability and Health: Children and
      Youth (ICF-CY) components. RESULTS: Thirty-three studies were identified, of
      which one, including 17 children with spastic CP, produced level II evidence, and
      the others, mainly non-controlled cohort studies, level IV and V. Outcomes at
      body function level were most frequently reported. Results suggest continuous ITB
      may be effective in reducing spasticity and dystonia in CP, as well as other
      neurological conditions, and may improve the ease of care and quality of life of
      children with CP, but the level of evidence is low. INTERPRETATION: Despite three
      decades of applying ITB in children and a relatively large number of studies
      investigating the treatment effects, a direct link has not yet been demonstrated
      because of the low scientific quality of the primary studies. Further
      investigation into the effects of continuous ITB at all levels of the ICF-CY is
      warranted. Although large, controlled trials may be difficult to realize,
      national and international collaborations may provide opportunities. Also,
      multicentre prospective cohort studies with a long-term follow-up, employing
      harmonized outcome measures, can offer prospects to expand our knowledge of the
      effects of continuous ITB therapy in children. WHAT THIS PAPER ADDS: There is low
      level evidence for continuous intrathecal baclofen (ITB) in children with
      cerebral palsy. Continuous ITB is effective in reducing spasticity and dystonia
      in non-controlled cohort studies. Evaluation of individual goals and systematic
      assessment of long-term effects in large cohort studies are required.

PMID- 30187920
TI  - Development and analytical validation of a radioimmunoassay for the
      quantification of alpha1 -proteinase inhibitor in serum and feces from the common
      marmoset (Callithrix jacchus).
AB  - BACKGROUND: The objective of this study was to develop and analytically validate
      a radioimmunoassay (RIA) for the measurement of alpha1 -proteinase inhibitor
      (alpha1 -PI) concentrations in serum and feces from the common marmoset. METHODS:
      Serum samples (n = 30) and 3-day fecal samples (n = 30) were obtained from
      healthy marmosets. An RIA was established and validated by determination of
      sensitivity, working range, dilutional parallelism, spiking recovery, and intra-
      and interassay variability. A reference interval for malpha1 -PI in serum and
      feces was established. RESULTS: Sensitivity and upper limit of the working range
      were 0.75 and 100.62 MUg/L, respectively. Observed-to-expected (O/E) ratios for
      serial dilutions ranged from 89.9% to 123.0% (mean +/-SD: 106.0 +/- 11.5%) for 8
      serum samples, and from 90.6% to 132.7% (mean +/-SD: 107.6 +/- 19.2%) for 4 fecal
      samples. O/E ratios for spiking recovery ranged from 97.6% to 104.4% (mean +/-SD:
      101.3 +/- 3%) for 4 serum samples, and from 97.5% to 101.4% (mean +/-SD: 99.2 +/-
      1.8%) for 4 fecal samples and 3 different spiking concentrations. Coefficients of
      variation (CV) for intra-assay variability for 8 serum samples ranged from 1.7%
      to 10.6% and 2.2% to 5.1% in the 8 fecal samples. The interassay CV for eight
      serum samples ranged from 1.3% to 9.9%, and from 1.0% to 6.7% in the 8 fecal
      samples. The reference interval in serum was determined to be 1047-1484 MUg/L.
      The reference interval in serum was determined to be 1047-1484 MUg/L. The
      reference interval for the 3-day mean fecal concentration, and 3-day maximum
      fecal concentration were determined to be 32.4-124.4 MUg/g and 39.1-158.7 MUg/g
      of feces, respectively. CONCLUSION: The developed assay is sensitive, linear,
      accurate, precise, and reproducible. Further studies are needed to determine the
      clinical utility of this assay.

PMID- 30187922
TI  - Eosinophilic aortitis with thoracic aortic aneurysm and rupture in a captive-born
      owl monkey.
AB  - Eosinophilic aortitis is a rare condition in animals and humans, and it has been
      occasionally reported associated with parasitic migration and with a poorly
      understood complex group of autoimmune vasculitides. Here, we describe a case of
      eosinophilic aortitis with thoracic aortic aneurysm and rupture in a captive-born
      owl monkey and discuss the differential diagnoses.

PMID- 30187923
TI  - Teaching and Learning Tips 12: Peer observation of teaching.
AB  - Challenge: How can clinical teachers continually improve their teaching skills?
      In addition to student feedback, peer and expert opinion can also provide
      valuable formative and evaluative feedback to guide self-improvement efforts.
      Here, we discuss ways to structure peer observation of teaching in dermatological
      settings and offer tips on how to optimize the learning experience for both the
      educator and peer observer.

PMID- 30187925
TI  - The Gross Motor Function Classification System: clinicians need to spread the
      word.

PMID- 30187924
TI  - Topical 5-fluorouracil in dermatologic disease.
AB  - BACKGROUND: 5-fluorouracil (5-FU) has proven to be an effective therapy in the
      treatment of a variety of dermatologic conditions. Approved by the United States
      Food and Drug Administration for the treatment of actinic keratoses and
      superficial basal cell carcinoma, topical 5-FU has also demonstrated efficacy in
      the treatment of a variety of other dermatologic diseases. METHODS: A search of
      the MEDLINE standard computer database, MEDLINE advanced database, and EMBASE
      database was conducted. RESULTS: Thirty-four articles met criteria for inclusion
      in this review. These articles represented 16 randomized controlled trials and 18
      case series. Each article was reviewed and summarized. CONCLUSIONS: Topical 5-FU
      is used in a variety of dermatologic disease processes with a wide range of
      efficacy and levels of evidence. Based on extent and level of evidence, our
      disease-specific systematic review found that the evidence is strongest for
      topical 5-FU use in the treatment of actinic keratosis, squamous cell carcinoma,
      and basal cell carcinoma. This review serves as a comprehensive summary of
      topical 5-FU use in dermatology.

PMID- 30187926
TI  - Long-term course of difficulty in participation of individuals with cerebral
      palsy aged 16 to 34 years: a prospective cohort study.
AB  - AIM: To determine the long-term course of difficulty in participation of
      individuals with cerebral palsy (CP) without intellectual disability between 16
      years and 34 years of age. METHOD: One hundred and fifty-one individuals with CP
      aged 16 to 20 years were included (63% male, 37% female; Gross Motor Function
      Classification System [GMFCS] levels I-IV; without intellectual disability). The
      Assessment of Life Habits questionnaire 3.0 general short form was used up to
      three times biennially and at 13-year follow-up (13-year follow-up: n=98). Scores
      (range 0-10) reflect difficulty and assistance in participation in housing,
      education and employment, interpersonal relationships, recreation, community
      life, and responsibilities. Multilevel models were used to determine the course
      of difficulty in participation by GMFCS level. RESULTS: Despite high average
      participation levels, 41% to 95% of adolescents and young adults with CP
      experienced difficulty. Difficulty in participation in housing and interpersonal
      relationships increased from age 16 years onwards and in most other life areas in
      the mid- and late 20s. In adolescents in GMFCS levels III and IV, participation
      in recreation and community life improved up to age 23 years. INTERPRETATION:
      Individuals with CP experience increasing difficulties in participation in their
      mid- and late 20s. Clinicians should systematically check for participation
      difficulties in young adults with CP and offer timely personalized treatment.
      WHAT THIS PAPER ADDS: Many individuals with cerebral palsy (CP) aged 16 to 34
      years experience difficulty in participation. Difficulty in participation
      increases in the mid- and late 20s for individuals with CP. Participation in
      recreation/community life improves before age 23 years for those in Gross Motor
      Function Classification System levels III and IV.

PMID- 30187927
TI  - Asc-1 transporter activation: an alternative to rescue age-related alterations in
      functional plasticity at rat hippocampal CA3/CA1 synapses.
AB  - Activation of the N-methyl-D-aspartate subtype of glutamate receptor (NMDA-R)
      represents a key functional process for memory formation. A decreased synthesis
      of the NMDA-R co-agonist d-serine was recently proposed to contribute to
      alterations of hippocampus-dependent memory mechanisms with ageing. Nevertheless,
      other pathways could also be involved and thus considered to be targets of
      interest to prevent cognitive ageing. Herein, we demonstrate that the Asc-1
      subtype of neutral amino acid (nAA) transporters that regulates d-serine and
      glycine release from neurons could be viewed as one of these targets. At CA3/CA1
      hippocampal synapses, Asc-1 activation did not modify basal glutamate
      neurotransmission either in adult or aged rats. In contrast, Asc-1 activation
      significantly increased NMDA-R-dependent long-term potentiation (LTP) in both
      groups of animals and fully rescued the age-related LTP deficits. This rescue in
      aged animals was observed only when Asc-1 activation was selectively managed by d
      Isoleucine (d-Ile), but not when less specifically driven by a mixture of nAA.
      Similarly, while any activation of Asc-1 improved the isolated NMDA-R-induced
      synaptic potentials in adult rats, only d-Ile was efficient in aged animals.
      Taken together, these results strengthen the interest in specifically targeting
      Asc-1 transporters to better cure age-associated memory decline. OPEN PRACTICES:
      This article has received a badge for *Open Materials* because it provided all
      relevant information to reproduce the study in the manuscript. The complete Open
      Science Disclosure form for this article can be found at the end of the article.
      More information about the Open Practices badges can be found at
      https://cos.io/our-services/open-science-badges/.

PMID- 30187928
TI  - Thorax x-ray and CT interventional dataset for nonrigid 2D/3D image registration
      evaluation.
AB  - PURPOSE: The aim of this paper is to provide a novel, publicly available standard
      image dataset with a useful evaluation framework for assessing nonrigid two
      /three-dimensional (2D/3D) registration algorithms. ACQUISITION AND VALIDATION
      METHODS: A pig lung model was used to obtain the image dataset. Inflated with
      different amounts of oxygen, a sequence of 3D volume data was acquired with
      computed tomography (CT), which ideally simulated different respiratory phases.
      With the model inflated and kept in certain states, 3D CT, 2D CT scout image and
      2D x-ray were acquired for the same respiratory phases, making them suitable to
      establish the evaluation dataset for 2D/3D registration algorithms. A total of
      120 well-distributed landmarks in every 3D volume were manually annotated and
      checked by several radiologists using semi-automatic software to generate the
      dataset. DATA FORMAT AND USAGE NOTES: All 3D image data were stored in both DICOM
      and ITK Meta format, and 2D image data were stored in DICOM format. A total of
      120 landmarks were manually annotated for each 3D image. Among these landmarks,
      eight landmarks located on large branch of the bronchial tree were also annotated
      in 2D images. The landmark coordinates were stored in a text file. The detailed
      usage including a standard evaluation framework for the proposed dataset is also
      provided. The dataset can be downloaded from the Zenodo repository
      (https://doi.org/10.5281/zenodo.997887). POTENTIAL APPLICATIONS: Our standard
      dataset was acquired with advanced clinical imaging devices and is quite suitable
      for quantitatively evaluating state-of-art, nonrigid 2D/3D registration
      algorithms.

PMID- 30187930
TI  - Pilates for low back pain.

PMID- 30187929
TI  - Quantitative determination of six steroid alkaloids by sensitive hydrophilic
      interaction liquid chromatography electrospray ionization mass spectrometry and
      its application to pharmacokinetic study in rats.
AB  - In this study, a sensitive hydrophilic interaction liquid chromatography (HILIC)
      method was developed to determine pseudojervine (PJV), veratrosine (VTS), jervine
      (JV), veratramine (VTM), veramarine (VA) and veratroylzygadenine (VTG) in rat
      plasma. Separations were carried out using LC-MS/MS with a Chrom Matrix HP amide
      column (5 m, 10 cm * 3.0 mm i.d.). The mobile phases were (A) 0.01 mm formic acid
      and (B) acetonitrile. Good linearity was found for all analytes (R2  > 0.995) in
      the concentration range from 5 to 1000 MUg/L with LLOQ at 5 MUg/L for VTM and
      VTS; and from 1 to 1000 MUg/L with LLOQ at 1 MUg/L for PJV, JV, VA and VTG.
      Accuracy of the assay varied from 90.5 to 108.1%. The extraction recovery and
      matrix effect of six analytes ranged from 72.2 to 95.5% and from 79.2 to 98.4%.
      According to the stability test, six analytes in rat plasma were stable during
      the analysis process. On the basis of validation of the assay, the
      pharmacokinetics of the six steroid alkaloids were investigated after oral
      administration of Lilu extracts to rats.

PMID- 30187931
TI  - The repressor and co-activator HsfB1 regulates the major heat stress
      transcription factors in tomato.
AB  - Plants code for a multitude of heat stress transcription factors (Hsfs). Three of
      them act as central regulators of heat stress (HS) response in tomato (Solanum
      lycopersicum). HsfA1a regulates the initial response, and HsfA2 controls acquired
      thermotolerance. HsfB1 is a transcriptional repressor but can also act as co
      activator of HsfA1a. Currently, the mode of action and the relevance of the dual
      function of HsfB1 remain elusive. We examined this in HsfB1 overexpression or
      suppression transgenic tomato lines. Proteome analysis revealed that HsfB1
      overexpression stimulates the co-activator function of HsfB1 and consequently the
      accumulation of HS-related proteins under non-stress conditions. Plants with
      enhanced levels of HsfB1 show aberrant growth and development but enhanced
      thermotolerance. HsfB1 suppression has no significant effect prior to stress.
      Upon HS, HsfB1 suppression strongly enhances the induction of heat shock proteins
      due to the higher activity of other HS-induced Hsfs, resulting in increased
      thermotolerance compared with wild-type. Thereby, HsfB1 acts as co-activator of
      HsfA1a for several Hsps, but as a transcriptional repressor on other Hsfs,
      including HsfA1b and HsfA2. The dual function explains the activation of
      chaperones to enhance protection and regulate the balance between growth and
      stress response upon deviations from the homeostatic levels of HsfB1.

PMID- 30187932
TI  - Temperature sensitive regions of the Chinook salmon vertebral column: Vestiges
      and meristic variation.
AB  - Variation of vertebral centra numbers is common in vertebrates. Likewise, the
      number of associated elements such as ribs and neural and haemal arches can vary
      and affect all regions of the vertebral column. In mammals, only the number of
      cervical vertebrae is invariable. Variation of total vertebral centra numbers is
      well documented in teleost fish, often related to temperature. Less information
      is available about which part of the vertebral column and which associated
      elements are liable to variation. Here, variation in number of vertebral centra
      and associated elements is studied in Chinook salmon in six distinct anatomical
      regions. Animals are raised at 8 and 12 degrees C to ask whether the vertebral
      centrum numbers, the pattern, and the frequency of variation in particular
      regions are temperature dependent. No significant difference concerning the total
      number of vertebrae was found, but regional differences occurred between the 8
      and 12 degrees C groups. Twelve specimens out of 60 of the 12 degrees C group had
      three postcranial vertebrae compared to only one specimen in the 8 degrees C
      group. The number of transitional vertebrae is significantly different in 8 and
      12 degrees C specimens. Fewer transitional vertebrae occur in more anterior
      positions in 8 degrees C specimens. Most specimens of both temperature groups had
      two ural centra; however 17 specimens out of 60 of the 12 degrees C group had up
      to five ural centra. Specimens of the 12 degrees C group show more variation in
      the presence of the vestigial ribs associated with transitional vertebrae.
      Clearly, the postcranial, transitional, and ural regions are temperature
      sensitive. This study shows that nonsignificant differences in the total number
      of vertebrae can mask significant regional variation. Variation of vertebral
      numbers could be the consequence of loss or gain of vertebral centra and/or a
      change in the identity of the associated element on the vertebral centrum.

PMID- 30187933
TI  - Genotype-phenotype correlation and risk stratification in a cohort of 123
      hereditary stomatocytosis patients.
AB  - Hereditary stomatocytoses (HSts) are a wide spectrum of hemolytic anemias in
      which the erythrocyte membrane cation permeability is increased. Dehydrated
      hereditary stomatocytosis is the most frequent among HSts. It is caused by
      missense mutations in PIEZO1 and KCNN4 genes. We described 123 patients enrolled
      in our Genetic Unit from 2013 to 2017. Overall HSt subjects exhibit macrocytic
      mild anemia. We found that PIEZO1 is the most frequent mutated gene within our
      families (47% of pedigrees). In 59.1% of cases the mutations localized in the
      nonpore protein domain, while in 40.9% of patients they localized in the central
      pore region. The genotype-phenotype correlation analysis on 29 PIEZO1-patients
      demonstrated that most of severely affected patients carried mutations in the
      pore domain, suggesting that the severity of this condition is related to the
      pore properties and intracellular domain that could be responsible of
      interactions with intracellular components. This is the first cohort study on a
      large set of hereditary stomatocytosis patients, stratified according to their
      causative gene useful for diagnosis, prognosis, and management of these patients.

PMID- 30187934
TI  - Isometric growth in the world's largest bony fishes (genus Mola)? Morphological
      insights from fisheries bycatch data.
AB  - For teleost fishes, the relationship between morphometric traits can provide
      significant insight into species life history, however gathering such data for
      noncommercial species can prove challenging. Here, we use data collected
      opportunistically from fisheries bycatch and stranding events to assess growth
      scaling over orders of magnitude in the ocean sunfish (genus Mola). Intriguingly,
      the confidence intervals for the relationship between length and mass suggests
      that isometric scaling is likely, a growth pattern rarely observed in fishes
      owing to the scaling of supportive structures. These data also enabled assessment
      of geometric morphometrics, which indicated that Mola sp shape varies subtly but
      significantly ontogenetically, with increased fin area comparative to body area
      as fish increase in size. More practically, total length emerged as an effective
      predictor for a range of morphological traits, including mass, fin lengths and
      surface area, which can provide vital baseline data for fisheries modeling and
      management.

PMID- 30187935
TI  - A dose-ranging study of ticagrelor in children aged 3-17 years with sickle cell
      disease: A 2-part phase 2 study.
AB  - Antiplatelet treatment is a potential therapeutic approach for sickle cell
      disease (SCD). Ticagrelor inhibits platelet aggregation and is approved for
      adults with acute coronary syndrome and following myocardial infarction. HESTIA1
      (NCT02214121) was a 2-part, phase 2 dose-finding study generating ticagrelor
      exposure, platelet inhibition, and safety data in children with SCD (3-17 years).
      In part A (n = 45), patients received 2 ticagrelor single doses, 0.125-2.25 mg/kg
      (washout >=7 days), then 7 days of twice-daily (bid) dosing with 0.125, 0.563, or
      0.75 mg/kg. In the 4-week blinded Part B extension (optional), patients received
      ticagrelor (0.125, 0.563, or 0.75 mg/kg bid; n = 16) or placebo (n = 7). Platelet
      reactivity decreased from baseline to 2 hours postdosing, and returned to near
      baseline after 6 hours postdosing. Dose-dependent platelet inhibition was seen
      with ticagrelor; mean relative P2Y12 reaction unit inhibition 2 hours after a
      single dose ranged from 6% (0.125 mg/kg) to 73% (2.25 mg/kg). Ticagrelor plasma
      exposure increased approximately dose proportionally. No patients experienced a
      hemorrhagic event during treatment. No differences were seen between groups in
      pain ratings and analgesic use during Part B. Ticagrelor was well tolerated with
      no safety concerns, no discontinuations due to adverse events (AEs), and reported
      AEs were mainly due to SCD. In conclusion, a dose-exposure-response relationship
      for ticagrelor was demonstrated in children with SCD for the first time. These
      data are important for future pediatric studies of the efficacy and safety of
      ticagrelor in SCD.

PMID- 30187936
TI  - The near disappearance of fetal hydrops in relation to current state-of-the-art
      management of red cell alloimmunization.
AB  - OBJECTIVE: In this study, we aim to evaluate trends in the condition of fetuses
      and neonates with hemolytic disease at the time of first intrauterine transfusion
      (IUT) and at birth, in relation to routine first-trimester antibody screening,
      referral guidelines, and centralization of fetal therapy. METHOD: We conducted a
      30-year cohort study including all women and fetuses treated with IUT for red
      cell alloimmunization at the Dutch national referral center for fetal therapy.
      RESULTS: Six hundred forty-five fetuses received 1852 transfusions between 1
      January 1987 and 31 December 2016. After the introduction of routine first
      trimester antibody screening, the hydrops rate declined from 39% to 15% (OR
      0.284, 95% CI, 0.19-0.42, P < 0.001). In the last time cohort, only one fetus
      presented with severe hydrops (OR 0.482, 95% CI, 0.38-0.62, P < 0.001). Infants
      are born less often <32 weeks (OR 0.572, 95% CI, 0.39-0.83, P = 0.004) and with
      higher neonatal hemoglobin (P < 0.001). Neonatal hemoglobin was positively
      independently associated with gestational age at birth, fetal hemoglobin, and
      additional intraperitoneal transfusion at last IUT. CONCLUSION: Severe alloimmune
      hydrops, a formerly often lethal condition, has practically disappeared, most
      likely as a result of the introduction of routine early alloantibody screening,
      use of national guidelines, and pooling of expertise in national reference
      laboratories and a referral center for fetal therapy.

PMID- 30187938
TI  - Comparative morphology of male genitalic structures in the minute litter bugs
      Dipsocoromorpha (Insecta: Hemiptera: Heteroptera).
AB  - Insect male genitalia show an evolutionarily variable morphology that has proven
      to be valuable for both, species identifications and phylogenetic analyses at
      higher taxonomic levels. Accurate usage of genitalic characters in taxonomic
      descriptions and phylogenetic analyses depends on consistency of terminology and
      validity of homology hypotheses. Both areas are underdeveloped in many insect
      groups. We here document the morphology and advance homology hypotheses of male
      genitalic features for the hemipteran infraorder Dipsocoromorpha, the minute
      litter bugs. Genitalic structures and the pregenital abdomen in Dipsocoromorpha
      are strikingly modified and diverse compared to other Heteroptera. In addition to
      variation in the shape of phallic structures (parameres and aedeagus), minute
      litter bug genitalia vary in the direction and degree of asymmetry and feature a
      plethora of processes derived from various abdominal segments with significant
      variation at low taxonomic levels. Here, male genitalic structures for an
      extensive taxonomic sample (32 genera and 71 specimens) are documented using
      scanning electron and confocal microscopy, and a universal terminology for
      genitalic structures across minute litter bugs is established that will
      facilitate species discovery and evolutionary research. We conclude by proposing
      primary homology hypotheses across the infraorder that now can be tested in a
      phylogenetic framework.

PMID- 30187937
TI  - Oral health-related quality of life as a predictor of subjective well-being among
      older adults-A decade-long longitudinal cohort study.
AB  - OBJECTIVE: The objective of this study was to evaluate possible longitudinal
      associations between oral health-related quality of life (OHRQoL) and subjective
      well-being among quinquagenarians and septuagenarians over up to 10 years of
      clinical observation. METHODS: This research is part of the "Interdisciplinary
      Study on Adult Development and Aging (ILSE)." All participants lived in an urban
      region of southwest Germany. One hundred and fifty-two participants born in 1930
      1932 (older cohort, OC; n = 54) and 1950-1952 (younger cohort, YC; n = 98)
      underwent comprehensive psychological, medical and dental examinations at
      baseline and up to 10 years thereafter. The Geriatric Oral Health Assessment
      Index (GOHAI) was used to assess OHRQoL. The Philadelphia Geriatric Center Morale
      Scale (PGCMS), general life satisfaction (GLS) and individuals' general
      satisfaction with their health (SWH) were used to evaluate subjective well-being.
      Regression models and structural equation modelling (SEM) were used to analyse
      the longitudinal associations between OHRQoL and subjective well-being. RESULTS:
      A cross-lagged prediction model revealed a positive association between baseline
      OHRQoL and subjective well-being across 10 years for both birth cohorts, OC [0.49
      (0.21; 0.69)] and YC [0.36 (0.24; 0.52)]. However, higher subjective well-being
      at baseline was not a predictor of better OHRQoL 10 years later for either
      cohort. CONCLUSIONS: OHRQoL seems to be a substantial predictor of subjective
      well-being in quinquagenarians and septuagenarians across the rather long
      observational period. Further studies with larger sample sizes are required to
      confirm this finding.

PMID- 30187939
TI  - Tooth loss in periodontally compromised patients: Results 20 years after active
      periodontal therapy.
AB  - AIM: To assess tooth loss in periodontally compromised patients 20 years after
      active periodontal therapy (APT) and to detect potential influencing factors for
      tooth loss on patient level. MATERIAL AND METHODS: From a total of 100 patients,
      who were re-evaluated ten years after APT, 70 could be re-examined 20 years +/-
      12 months after APT. Tooth loss during 20 years was detected and based on
      regression analyses the impact of patient-levelled factors was estimated.
      RESULTS: Of 1.639 teeth, 201 were lost (mean 2.87 teeth/patient, range 0-19
      teeth, SD 3.49), resulting in a mean tooth loss rate of 0.14 teeth/patient/year
      during 20 years. Mean tooth loss per patient was higher during the second ten
      years of supportive periodontal therapy (SPT) compared to the first (1.20 vs.
      1.67 teeth/patient). As influencing factors age (p < 0.001), smoking (p < 0.001),
      compliance to SPT (p < 0.001), marital status (p < 0.001), presence of diabetes
      (p < 0.001) and heart diseases (p = 0.001) could be detected. CONCLUSION: Over 20
      years of follow-up, a low number of teeth were lost in mostly severely
      compromised periodontal patients. Smoking, non-compliance to SPT, age, living as
      a single and systemic diseases like diabetes or cardiovascular diseases
      negatively influence tooth loss on the long run.

PMID- 30187940
TI  - Morphometric analysis of the gastrointestinal tract of four African muroid rodent
      species (Rhabdomys dilectus, Rhabdomys pumilio, Aethomys chrysophilus, and
      Lemniscomys rosalia).
AB  - Several muroid rodent species are distributed throughout southern Africa. Some
      species are reportedly classified as opportunistic omnivorous rodents consuming
      plant, seed, and insect material. This study aims to provide a detailed
      morphometric analysis of the gastrointestinal tract (GIT) of four such omnivorous
      species, including stomach content analysis. Fixed GIT specimens (n = 5 of each)
      of Rhabdomys dilectus (Mesic four-striped grass mouse), Rhabdomys pumilio (Xeric
      four-striped grass mouse), Aethomys chrysophilus (Red rock rat), and Lemniscomys
      rosalia (Single-striped grass mouse) were weighed. Length and circumference
      measurements of each anatomically distinct GIT region were determined to
      calculate the basal surface area (BSA). Histological sections from each GIT
      region were used to calculate a surface enlargement factor (SEF). The BSA and SEF
      were multiplied to calculate the luminal surface area (LSA) of each GIT region.
      Stomach content was analyzed both macroscopically and histologically. All species
      had a similar GIT morphology, namely a unilocular, hemiglandular stomach with a
      clear limiting ridge, which indicated the transition from stratified squamous
      epithelium to glandular epithelium. A large loosely spiralled cecum was present
      in all species. A narrowing of the cecal apex accompanied by lymph aggregates,
      confirmed histologically in both Rhabdomys species, indicated a cecal appendix. A
      single short colonic loop with a unique folding pattern for each species was
      present in the proximal colon. The colonic mucosal surface presented with
      proximal V-shaped, and distal longitudinal folds. Intermediate transitional S
      shaped folds were present in three species (R. dilectus, R. pumilio, and L.
      rosalia). Colonic mucosal folds indicated hindgut specialization similar to other
      muroid rodents. The hindgut specialization was further supported by morphometric
      analysis, which indicated large BSA and LSA measurements in the cecum and colon.
      These adaptations are consistent with herbivory, despite stomach content analysis
      revealing omnivorous tendencies.

PMID- 30187941
TI  - Responsiveness to change of the Malay-ECOHIS following treatment of early
      childhood caries under general anaesthesia.
AB  - OBJECTIVES: To evaluate the sensitivity and responsiveness of the Malay version
      of Early Childhood Oral Health Impact Scale (Malay-ECOHIS) to dental treatment of
      early childhood caries (ECC) under general anaesthesia (GA) and determine the
      minimally important difference (MID) for the Malay-ECOHIS. METHODS: A sample of
      158 preschool children with ECC awaiting dental treatment under GA was recruited
      over an 8-month period. Parents self-completed the Malay-ECOHIS before and 4
      weeks after their child's dental treatment. At 4 weeks follow-up, parents also
      responded to a global health transition judgement item. Data were analysed using
      independent and paired samples t tests, ANOVA and Pearson correlation
      coefficients. RESULTS: The response rate was 87.3%. The final sample comprised 76
      male (55.1%) and 62 female (44.9%) preschool children with mean age of 4.5 (SD =
      1.0) years. Following treatment, there were significant reductions in mean scores
      for total Malay-ECOHIS, child impact section (CIS), family impact section (FIS)
      and all domains, respectively (P < 0.001). The effect size (ES) for the Malay
      ECOHIS was +1.0; across the domains, it ranged from +0.4 to +1.9. There was a
      weak, positive correlation for Malay-ECOHIS change scores (r = 0.165) and CIS
      change scores (r = 0.175) with the number of decayed teeth (dt), respectively.
      Similar correlation was also observed between Malay-ECOHIS change scores and the
      number of extracted teeth (r = 0.129). Based on the global health transition
      judgement, 62.3% of parents reported their child's oral condition to be "a little
      improved" while 37.7% reported it to be "much improved" following treatment, with
      Malay-ECOHIS mean change scores of 6.7 (ES = +1.1) and 9.6 (ES = +1.2),
      respectively. There was an observed gradient in the Malay-ECOHIS change scores
      and ES in relation to parents' perception of their child's oral health
      improvement after treatment, supporting the responsiveness of the measure. The
      Malay-ECOHIS MID was found to be 7 scale points. CONCLUSION: The Malay-ECOHIS is
      empirically shown to be sensitive and responsiveness to dental treatment of ECC
      under GA.

PMID- 30187942
TI  - Thrombopoietin level predicts response to treatment with eltrombopag and
      romiplostim in immune thrombocytopenia.
AB  - Thrombopoietin receptor agonists (TPO-RAs) are used to treat immune
      thrombocytopenia (ITP), but predicting clinical response to TPO-RAs before
      initiation is not possible. To determine whether endogenous TPO levels predict
      treatment response to TPO-RAs we performed a retrospective analysis of ITP
      patients with known baseline TPO levels who received TPO-RAs. Data was collected
      for ITP patients with a baseline TPO level treated with eltrombopag or
      romiplostim. Multiple logistic regression was used to model the probability of 3
      classes of treatment response (overall, moderate, and superior) based on TPO
      level; receiver operating characteristic (ROC) analysis was performed to identify
      optimal TPO thresholds for response; correlations between TPO level and various
      response characteristics were analyzed. A total of 67 patients (37 receiving
      eltrombopag and 46 receiving romiplostim) were included. Logistic regression
      models demonstrated a significant predictive relation between TPO level and
      probability of all classes of response; per 10 pg/mL TPO increase, odds ratio for
      overall response to eltrombopag was 0.524 (95% CI 0.327, 0.837) and romiplostim
      was 0.905 (95% CI, 0.844, 0.970). TPO level was inversely correlated with all
      classes of response; for overall response, r = -0.719 (P < .001) for eltrombopag
      and r = -0.584 (P < .001) for romiplostim. ROC analysis identified TPO thresholds
      of <=136 pg/mL (eltrombopag) and <=209 pg/mL (romiplostim) as optimally
      discriminating between responders and nonresponders. Most non-responders had high
      TPO levels but did respond after addition of low-dose prednisone. In conclusion,
      TPO levels predict response to eltrombopag and romiplostim in ITP patients, with
      lower levels predicting improved probability and magnitude of response.

PMID- 30187943
TI  - Infant nest and stash sites of variegated lemurs (Varecia rubra): The extended
      phenotype.
AB  - Very few primate species give birth to litters and build nests in which to care
      for them. Those that do are small-bodied, nocturnal, and solitary. Variegated
      lemurs are exceptional in that they bear litters in arboreal nests, yet are
      relatively large-bodied, day-active, and gregarious. Furthermore, they raise
      their young cooperatively and practice absentee parenting; non-clinging young are
      transported orally and periodically stashed in arboreal spots that are
      supportive, sheltered, and usually concealed. Following birth, infant nest and
      stash trees were mapped, measured, and taxonomically identified in a population
      of red variegated lemurs in Masoala National Park. About 40 trees were used per
      litter for nesting and stashing young in adjacent, non-overlapping core areas
      within the community. These were the largest trees in the forest, even larger
      than those used for feeding. Furthermore, most occur in valleys and are laced
      with lianas, creating sites that buffer young from predation, accidental falls,
      and to some degree, thermal stress. In combination, the number of nest and stash
      trees used per litter, their characteristics, and their geo-spatial arrangement
      indicate that such sites are both select and limited in the landscape, exposing
      the dependence of red variegated lemurs on intact forest canopies for raising non
      clinging young within the context of an absentee parenting system. Nest and stash
      sites are in effect Varecia's extended phenotype. Logging of large trees in
      Madagascar's eastern rain forests is considered a major factor resulting in local
      extinctions of variegated lemurs because they rely heavily upon large, mature
      trees for fruit. However, this study suggests that removal of large trees may
      more directly precipitate local extinctions by impeding their ability to
      reproduce. Long-term survival of red variegated lemurs will depend upon efforts
      to end harmful timber extraction in its remaining stronghold, the Masoala
      Peninsula.

PMID- 30187944
TI  - Locally produced CD19 CAR T cells leading to clinical remissions in medullary and
      extramedullary relapsed acute lymphoblastic leukemia.
AB  - Autologous CD19 chimeric-antigen receptor (CAR) T cells demonstrated remarkable
      remission rates in relapsed and refractory acute lymphoblastic leukemia (R/R
      ALL). Here, we report results from a phase 1b/2 study of in-house produced CD19
      CAR with a CD28 costimulatory domain. Twenty-one patients with R/R ALL were
      enrolled, and 20 infused. The median age was 11 years (range, 5-48). Patients had
      a median of 4 prior regimens, including blinatumomab in 6 and prior stem-cell
      transplantation in 10. In total 8 patients had extramedullary (EM) leukemic
      involvement, and prior to lymphodepletion and CAR 7 had active lesions, a group
      underrepresented in previous trials. In vivo expansion of CAR T cells was
      observed in 18 patients. In total 16 patients developed cytokine release
      syndrome, and 11 patients developed neurotoxicity, with no toxic deaths. All
      responding patients were referred to an allogeneic hematopoietic stem-cell
      transplantation. The remission rate was 90%, including resolution of all
      refractory EM sites. Four responding patients relapsed, 3 who had a PCR-MRD
      positive remission at 28 days following CAR-T cells and 1 patient 21 months after
      an MRD-negative response. The estimated 1-year event-free survival and overall
      survival are 73% and 90%, respectively. Patients with R/R EM ALL may also benefit
      from CAR-T cell therapy.

PMID- 30187945
TI  - A two-step culture method utilizing secreted luciferase recombinant virus for
      detection of anti-cytomegalovirus compounds.
AB  - Quantification of human cytomegalovirus (HCMV) replication by plaque assay
      reflects viral infectivity but has several drawbacks. Recombinant virus
      expressing reporter genes can facilitate quantification of HCMV replication. In
      this study, a recombinant virus, Towne-BAC(dTT)-MetLuc, was constructed and the
      secretable Metridia luciferase (MetLuc) gene inserted into it under UL146
      promoter. In addition, the UL130 gene was repaired to allow growth of the
      recombinant virus in both fibroblasts and epithelial cells. As predicted,
      luciferase activity was secreted into the culture medium and correlated with
      virus replication in infected fibroblasts and epithelial cells. Furthermore,
      secreted luciferase activity was correlated with the size of the recombinant
      virus inoculum with a dynamic range of 3 logs. This recombinant virus was used in
      a two-step culture protocol for detection of the anti-HCMV activity of compounds;
      that is, the supernatant of a first-step culture with anti-viral compounds was
      collected and inoculated into uninfected cells to create a second-step culture.
      Although secreted luciferase activity leaked in the first-step culture
      supernatant in the presence of some antiviral compounds, luciferase activity in
      the second-step culture supernatant reflected the virus yield in the first-step
      culture. Therefore, comparison of luciferase activity in the first- and second
      step cultures indicated the anti-viral activity of the compounds. This two-step
      culture protocol facilitates screening of anti-viral compounds.

PMID- 30187946
TI  - Allyl rhodanine azo dye derivatives: Potential antimicrobials target d-alanyl
      carrier protein ligase and nucleoside diphosphate kinase.
AB  - 3-Allyl-5-(4-arylazo)-2-thioxothiazolidine-4-one (HLn ) ligands (where n = 1 to
      3) were hypothesized to have antimicrobial activities mediated through inhibition
      of new antimicrobial targets. The ligands (HLn ) were synthesized and
      characterized by infrared (IR) and 1 H nuclear magnetic resonance (1 H NMR)
      spectra. The ligands (HLn ) were in silico screened to their potential inhibition
      to models of d-alanyl carrier protein ligase (DltA) (from Bacillus cereus, PDB
      code 3FCE) and nucleoside diphosphate kinase (NDK) (from Staphylococcus aureus;
      PDB code 3Q8U). HL3 ligand has the best energy and mode of binding to both NDK
      and DltA, even though its binding to DltA was stronger than that to NDK. In
      antimicrobial activity of HL3 ligand, morphological and cytological changes in
      HL3 -treated bacteria agreed with the in silico results. The HL3 ligand showed
      significant antimicrobial activity against B. cereus, S. aureus, and Fusarium
      oxysporium. The HL3 -treated bacterial cells appeared malformed and incompletely
      separated. Its cell walls appeared electron-lucent and ruptured. They contained
      more mesosomes than normal cells. It was found that the HL3 ligand represented as
      a bactericide against B. cereus and S. aureusby blocking target DltA, and may
      target NDK.

PMID- 30187947
TI  - MiR-134-5p attenuates neuropathic pain progression through targeting Twist1.
AB  - Neuropathic pain is a kind of chronic pain because of dysfunctions of
      somatosensory nerve system. Recently, many studies have demonstrated that
      microRNAs (miRs) play crucial roles in neuropathic pain development. This study
      was designed to investigate the effects of miR-134-5p on the process of
      neuropathic pain progression in a rat model established by chronic sciatic nerve
      injury (CCI). First, we observed that miR-134-5p was significantly decreased in
      CCI rat models. Overexpression of miR-134-5p strongly alleviated neuropathic pain
      behaviors including mechanical and thermal hyperalgesia. Meanwhile, inflammatory
      cytokine expression, such as IL-6, IL-1beta and TNF-alpha in CCI rats were
      greatly repressed by upregulation of miR-134-5p. Twist1 has been widely regarded
      as a poor prognosis biomarker in diverse diseases. Here, by using bioinformatic
      analysis, 3'-untranslated region (UTR) of Twist1 was predicted to be a downstream
      target of miR-134-5p in our study. Here, we found that overexpression of miR-134
      5p was able to suppress Twist1 dramatically. Furthermore, it was exhibited that
      Twist1 was increased in CCI rats time-dependently and Twist1 was inhibited in
      vivo. Subsequently, downregulation of Twist1 in CCI rats could depress
      neuropathic pain progression via inhibiting neuroinflammation. In conclusion, our
      current study indicated that miR-134-5p may inhibit neuropathic pain development
      through targeting Twist1. Our findings suggested that miR-134-5p might provide a
      novel therapeutic target for neuropathic pain.

PMID- 30187948
TI  - Absence of effect of the antiretrovirals Duovir and Viraday on mitochondrial
      bioenergetics.
AB  - Most toxicity associated with antiretroviral drugs is thought to result from
      disruption of mitochondrial function. Unfortunately, there are no validated
      laboratory markers for clinically assessing the onset of mitochondrial toxicity
      associated with antiretroviral therapy. In a previous study on mitochondrial
      hepatocytes, the protease inhibitor lopimune was shown to induce mitochondrial
      toxicity by increasing reactive oxygen species (ROS) production and decreasing
      respiratory control ratio (RCR) reflecting compromised mitochondrial efficiency
      in adenosine triphosphate production. Mitochondrial dysfunction and ROS
      production were directly correlated with the expression of uncoupling protein 2
      (UCP2). In the current study we aim to determine the toxicity of nucleoside or
      nucleotide and nonnucleoside reverse-transcriptase inhibitors, Duovir and Viraday
      on liver mitochondria isolated from treated mice by monitoring UCP2 expression.
      Our results showed that both Duovir and Viraday had no effect on mitochondrial
      respiration states 2, 3, 4, and on RCR. In addition, ROS generation and UCP2
      expression were not affected. In conclusion, our results indicate the difference
      in the mechanism of action of distinct classes of antiretroviral drugs on
      mitochondrial functions and may associate UCP2 expression with subclinical
      mitochondrial damage as marker of cellular oxidative stress.

PMID- 30187949
TI  - Restoration of GATA4 expression impedes breast cancer progression by
      transcriptional repression of ReLA and inhibition of NF-kappaB signaling.
AB  - There are increasing reports of aberrant expression of GATA4, correlated with
      oncogenesis and malignant progression in some solid tumors, but whether GATA4
      functions as an oncogenic driver or a tumor suppressor in carcinogenesis remains
      controversial. Because the role and mechanism of GATA4 in breast cancer (BrCa)
      remain poorly understood, we focused on the expression of GATA4 in BrCa cell
      lines and tissues and its mechanism in breast oncogenesis. Semiquantitative real
      time polymerase chain reaction (RT-PCR), quantitative RT-PCR, Western blot
      analysis, and immunohistochemistry were used to detect expression of GATA4 in
      BrCa cell lines and adjacent breast tissues. Methylation statuses of the GATA4
      promoter were studied using methylation-specific PCR in BrCa cell lines.The
      effects of GATA4 on proliferation, invasion, and cell cycle were also analyzed.
      Compared with adjacent breast tissue, GATA4 expression in BrCa tissue and cell
      lines was obviously lower and low expression levels of GATA4 predicted poor
      outcome. Methylation of GATA4 occurred in almost all of BrCa cell lines . GATA4
      overexpression decreased viability, invasion, migration, and epithelial-to
      mesenchymal transition of MB-231 and BT549 cells, and markedly induced cell cycle
      arrest and apoptosis. Exogenous expression GATA4 accompanied a significant
      alteration of MMP2, MMP3, E-cadherin, and N-cadherin expression and induction of
      the caspase-8 pathway. Moreover, GATA4 could directly repress RelA (p65)
      transcription, reduce the nuclear phosphorylation-p65 and upregulate inhibitor
      kappa B expression. Altogether, GATA4 plays a tumor-suppressive role via
      repression of NF-kappaB signaling in BrCa cells. Our findings suggest that GATA4
      is a potential prognostic biomarker and gene therapeutic target for human BrCa.

PMID- 30187950
TI  - Comparison of urologic and non-urologic presentation in interstitial
      cystitis/bladder pain syndrome patients with and without Hunner lesions.
AB  - AIMS: To compare severity and characteristics of urologic pain, other urinary
      symptoms, sexual pain, psychosocial health, and the distribution and intensity of
      non-urologic pain between men and women with and without Hunner lesions. METHODS:
      All cystoscopies were performed and documented by the same clinician to ensure
      uniform recognition of Hunner lesions. Intensity of urologic and sexual pain,
      nocturia, frequency, urgency, and bladder hypersensitivity features were assessed
      using validated questionnaires and numeric rating scales. The distribution and
      intensity of non-urologic pain was assessed using self-reported history, a body
      map diagram, and numeric rating scales. Somatic symptom burden, depression, and
      anxiety were compared. RESULTS: Among the 150 participants, 27% (n = 41) had
      Hunner lesions (36% of men, 25% of women). Participants with Hunner lesions were
      significantly older (median age 58 vs 41, P < 0.001). They reported less intense
      urologic pain (5 vs 7, P = 0.024) and more nocturia (ICSI nocturia symptom score:
      4 vs 3, P = 0.007). They also were less likely to have a history of irritable
      bowel syndrome (15% vs 36%, P = 0.013) and anxiety attacks (22% vs 44%, P =
      0.013). Close to half of Hunner IC patients had non-urologic pain outside the
      pelvis. There were no differences in bladder hypersensitivity features (eg,
      painful bladder filling) between the two groups. CONCLUSIONS: Hunner lesions can
      be identified in both men and women. There are significant overlaps in terms of
      their urologic and non-urologic presentation. Further investigation is needed on
      phenotypic and biological distinction between IC/BPS with and without Hunner
      lesions.

PMID- 30187951
TI  - Improved sensitivity and temporal resolution in perfusion FMRI using velocity
      selective inversion ASL.
AB  - PURPOSE: This work aims to investigate the utility of velocity selective
      inversion pulses for perfusion weighted functional MRI. METHODS: Tracer kinetic
      properties of velocity selective inversion (VSI) pulses as an input function for
      an arterial spin labeling (ASL) experiment were characterized in a group of
      healthy participants. Numerical simulations were conducted to search for a robust
      set of timing parameters for FMRI time series acquisition with maximal signal to
      noise ratio efficiency. The performance of three VSI pulse sequences with
      different timing parameters was compared with a pseudocontinuous ASL sequence in
      a simple FMRI experiment conducted on healthy participants. RESULTS: The fit to
      the tracer kinetic model yielded arterial CBV of 1.24% +/- 0.52% and 0.45 +/-
      0.11% and perfusion rates of 60.8 +/- 32.3 and 34.4 +/- 5.4 mL/min/100 g for gray
      and white matter, respectively. Bolus arrival times were estimated as 75.7 +/- 21
      ms and 349 +/- 78 ms for gray and white matter, respectively. The FMRI
      experiments showed that VSI pulses yield comparable sensitivity to PCASL with
      similar timing parameters (TR = 4 s). However, VSI pulses could be used at a
      faster acquisition speed (TR = 3 s) and were more sensitive to neuronal activity
      than PCASL pulses, as evidenced by the 31% higher Z scores obtained on average in
      the active regions. CONCLUSION: VSI pulses can be very beneficial for perfusion
      weighted functional MRI because of their tracer kinetic characteristics, which
      allow a faster acquisition rate while maintaining an efficient labeling input
      function.

PMID- 30187952
TI  - Suppressing ROS-TFE3-dependent autophagy enhances ivermectin-induced apoptosis in
      human melanoma cells.
AB  - Melanoma is an aggressive skin malignancy with a high mortality rate; however,
      successful treatment remains a clinical challenge. Ivermectin, a broad-spectrum
      antiparasitic drug, has recently been characterized as a potential anticancer
      agent due to its observed antitumor effects. However, the molecular mechanisms of
      ivermectin remain poorly understood. In the current study, we tested the
      involvement of autophagy in the ivermectin mechanism of action in human melanoma
      cells. We exposed SK-MEL-28 cells to different concentrations of ivermectin (2.5,
      5, and 10 MUM) for 24 hours. Here, ivermectin-induced apoptosis, as evidenced by
      the upregulation of cleaved poly (ADP-ribose) polymerase, BAX expression, and
      caspase-3 activity and downregulation of BCL-2 expression. In line with the
      apoptosis response, ivermectin triggered autophagy. Pharmacological or genetic
      inhibition of autophagy further sensitized SK-MEL-28 cells to ivermectin-induced
      apoptosis. Mechanistically, ivermectin-induced TFE3(Ser321) dephosphorylation,
      activated TFE3 nuclear translocation and increased TFE3 reporter activity, which
      contributed to lysosomal biogenesis and the expression of autophagy-related
      genes, and subsequently, initiated autophagy in SK-MEL-28 cells. Moreover, N
      acetyl-cysteine, an reactive oxygen species (ROS) scavenger, abrogated the
      effects of ivermectin on TFE3-dependent autophagy. Taken together, we
      demonstrated that ivermectin increases TFE3-dependent autophagy through ROS
      signaling pathways in human melanoma cells and that inhibiting autophagy enhances
      ivermectin-induced apoptosis in human melanoma cells.

PMID- 30187953
TI  - The development of a patient-reported outcome measure for real-time symptom
      assessment in a population with functional urologic complaints-A focus group
      study.
AB  - AIMS: In the current diagnostic process for overactive bladder syndrome (OAB),
      biased retrospective questionnaires are often used. There is a need for a new
      assessment tool that embraces the heterogeneity of the OAB complex. A momentary
      assessment tool, the Experience Sampling Method (ESM) is promising, capturing
      random repetitive measurements during the day in the context of daily life and is
      capable to measure potential contextual triggers and psychological aspects. A
      focus group study was set up to evaluate which items should be implemented in a
      urological ESM. METHODS: Focus group interviews were arranged, to assess the
      suitability and comprehensibility of a newly developed urological patient
      reported outcome measurement (PROM), "Uromate." "Uromate" was created based on
      ESM literature. A multidisciplinary expert meeting was conducted to gain
      consensus on item relevance. RESULTS: The initial ESM questionnaire contained 58
      items, but was eventually reduced to 39 items after focus group sessions and
      expert meeting. Thirty-seven items are repeated questions, including three gender
      dependent items. Two items are one-time questions about the use of incontinence
      material. Additionally, a morning questionnaire was included. Depending on the
      symptom pattern, a minimum of 26 items and a maximum of 36 items will be
      repeatedly assessed with "Uromate." CONCLUSION: There is a need for a modern
      assessment tool for OAB which overcomes the limitations of today's retrospective
      questionnaires. Therefore, a urological ESM tool, the "Uromate," is being
      developed as a PROM, following the FDA PROM development guidelines, to measure
      real-time symptoms in the context of daily life.

PMID- 30187954
TI  - MicroRNA-125a suppresses cell migration, invasion, and regulates hyaluronic acid
      synthase 1 expression by targeting signal transducers and activators of
      transcription 3 in renal cell carcinoma cells.
AB  - Renal cell carcinoma (RCC) is one of the most common cancers in urology. MicroRNA
      125a (miR-125a) has been demonstrated to be implicated in various cancers.
      However, the functional role of miR-125a in RCC remains largely unclear. This
      study was aimed to investigate the functional role of miR-125a and the expression
      relevance of signal transducers and activators of transcription 3 (STAT3) with
      hyaluronic acid synthase 1 (HAS1) in RCC. We revealed that miR-125a was
      downexpressed in 786-O cells, and examined transfected efficiency. According to
      functional assay, overexpression of miR-125a inhibited cell migration and cell
      invasion, but no obvious effect was observed on cell proliferation. The
      luciferase activity assay showed that miR-125a could directly target STAT3 3'
      untranslated regions. Meanwhile, quantitative polymerase chain reaction (qPCR)
      assay and Western blot analysis demonstrated that miR-125a could inhibit STAT3
      expression at both messenger RNA and protein levels. Furthermore, the combination
      sites between STAT3 and HAS1 were predicted by prediction of transcription factor
      binding sites database analysis. The expression of STAT3 was correlated with HAS1
      expression, exemplified by the same tendency detected by qPCR assay. Taken
      together, our results preliminarily demonstrate that miR-125a could constrain
      cell migration, invasion, and regulate HAS1 expression in RCC cells by targeting
      STAT3. It is likely to facilitate a better understanding of the regulation
      mechanisms of miR-125a in RCC.

PMID- 30187955
TI  - A unique case of pressure-induced alopecia following EEG monitoring.
AB  - We report a unique case of pressure-induced alopecia (PIA) in a 11-year-old boy
      following the use of electroencephalogram (EEG) electrodes on the scalp for 4
      days. PIA is caused by localized ischemia leading to vascular congestion and
      discrete, often circumscribed patches of hair loss within 3-28 days of pressure
      interface. The synchronous conversion of follicles from anagen to catagen or
      telogen phase is the most distinctive finding of PIA. PIA is a nonscarring
      alopecia which often resolves over time without treatment.

PMID- 30187956
TI  - Subcutaneous fat necrosis of the newborn and associated hypercalcemia: A
      systematic review of the literature.
AB  - Subcutaneous fat necrosis of the newborn is an uncommon disorder, and although
      usually benign, associated hypercalcemia can lead to complications such as
      failure to thrive and renal failure. Many sources suggest screening for
      hypercalcemia for 6 months following resolution of skin lesions, but little data
      are available to support this recommendation. This study examines existing
      published literature to better guide practitioners regarding screening
      evaluations of asymptomatic patients with subcutaneous fat necrosis. A systematic
      review of the literature was conducted using a PubMed English literature search.
      Data from case reports and case series were collected regarding the presence of
      hypercalcemia and associated complications, birth history, and age of
      onset/resolution of skin lesions and laboratory abnormalities. Approximately half
      (51%) of infants reported had hypercalcemia. Most (77%) developed detectable
      hypercalcemia within 30 days of skin lesion onset, and 95% developed detectable
      hypercalcemia within 60 days of skin lesion onset. Hypercalcemia was detected in
      only 4% of patients > 70 days following onset of skin lesions. Seventy-six
      percent had resolution of hypercalcemia within 4 weeks of detection.
      Hypercalcemia was more prevalent in full-term vs pre-term infants (P-value =
      0.054), and higher birthweight was significantly associated with an increased
      risk of developing hypercalcemia (P-value = 0.022). Although gestational age
      trended toward significance, the only statistically significant clinical feature
      predicting the development of hypercalcemia was higher birthweight. Current
      recommendations for laboratory monitoring are not evidence-based, and this study
      provides interim data to guide practitioners until prospective, randomized
      controlled trials are conducted.

PMID- 30187957
TI  - In response to Peedin and Karp, "The definition of severe systemic lupus
      erythematosus needs clarification in the next ASFA guidelines".

PMID- 30187958
TI  - Diffuse cutaneous mastocytosis: Case report and literature review.
AB  - A 6-month-old boy was referred to our burn unit with a recurrent bullous
      dermatitis, fever, and emesis, originally diagnosed as staphylococcal scalded
      skin syndrome (SSSS) at an outside hospital. Infectious workup was negative and
      shave biopsy revealed a dense, diffuse dermal infiltrate of mast cells,
      consistent with diffuse cutaneous bullous mastocytosis-a rare variant of
      cutaneous mastocytosis. Treatment included a prolonged course of corticosteroids
      and antihistamines. Recognition of this rare form of mastocytosis is important,
      as it can be easily mistaken for other pediatric bullous diseases and is
      associated with life-threatening complications including vasodilation,
      anaphylactic shock, gastrointestinal bleeding, and death.

PMID- 30187960
TI  - MicroRNA-424 regulates epithelial-mesenchymal transition of endometrial carcinoma
      by directly targeting insulin-like growth factor 1 receptor.
AB  - Although numerous miRNAs are reported to contribute to the carcinogenesis of
      malignant tumor, the specific role of miR-424 in endometrial carcinoma is seldom
      reported. To explore the effect of miR-424 on epithelial-mesenchymal transition
      and its underlying mechanism, we detected miR-424 expression in endometrial
      carcinoma tissue and cells. We found that miR-424 was significantly downregulated
      in endometrial carcinoma tissues and cells, especially in HEC-1B cells. To
      perform the functional analysis, we transfected HEC-1B with miR-424-mi, miR-424
      inh, mi-control, and inh-control, respectively. We found that overexpression of
      miR-424 significantly decreases cell proliferation and migration, accompanied
      with the increased E-cadherin/Vimentin expression and the transition of
      mesenchymal to epithelial cell phenotype. We identified that insulin-like growth
      factor-1 receptor (IGF-1R) was a potential target of miR-424 by computational
      analysis followed by luciferase reporter assays. Of note, we found that the
      downregulation of miR-424 in HEC-1B cells enhanced endogenous IGF-1R expression.
      Further mechanistic analysis revealed that forced expression of IGF-1R in miR-424
      mim transfected cells remedied the weakened migration resulting from
      overexpression of IGF-1R. Taken together, the results of the current study
      demonstrated that miR-424 was a tumor suppressor for endometrial carcinoma and a
      favorable factor against tumor progression through targeting IGF-1R, thus
      providing a target for the treatment of endometrial carcinoma.

PMID- 30187959
TI  - Natural history and extracutaneous involvement of congenital morphea: Multicenter
      retrospective cohort study and literature review.
AB  - BACKGROUND: Congenital morphea is a form of localized scleroderma that presents
      at birth. There is limited information on its presentation and progression.
      METHODS: Patients with congenital morphea were identified from five pediatric
      dermatology and rheumatology tertiary care centers in Canada, the United States,
      and Italy from 2001 to 2016. Cases from the literature were identified by
      searching Ovid (EMBASE and MEDLINE) from inception to June 30, 2017. Disease
      characteristics and prevalence of extracutaneous involvement were analyzed.
      RESULTS: Thirteen patients were identified from the five centers, and 13 cases
      were described in the literature, representing 25 patients, with one duplication.
      Fourteen patients (56%) were female. Median age at diagnosis was 2.9 years
      (interquartile range 1.2-5.1 years). Linear morphea, including en coup de sabre
      and Parry-Romberg syndrome, was the most common subtype observed (n = 19, 76%),
      followed by circumscribed (n = 5, 20%), generalized (n = 2, 8%), and mixed (n =
      2, 8%). The face (n = 14, 56%), scalp (n = 8, 32%), and trunk (n = 6, 24%) were
      the most common locations affected. Most lesions were active at diagnosis (n =
      19, 76%), but all patients with follow-up later became inactive. Extracutaneous
      involvement was seen in 12 (48%) patients, all of whom had linear morphea.
      Musculoskeletal sequelae were seen in those with linear morphea of the
      extremities (4/5, 80%), and neurologic involvement was seen in those with linear
      morphea of the head (8/13, 62%). CONCLUSION: Congenital morphea is associated
      with extracutaneous manifestations and delayed diagnosis. More research is needed
      to determine whether early recognition, monitoring, and treatment can alter the
      disease course.

PMID- 30187961
TI  - Traction-assisted esophageal endoscopic submucosal dissection for treatment of
      squamous cell carcinoma involving a diverticulum.

PMID- 30187962
TI  - Thyroid dermopathy and acropachy in pediatric patients.
AB  - The extrathyroid manifestations of Graves disease (GD) include thyroid
      orbitopathy, dermopathy, and acropachy. Thyroid dermopathy (TD), also known as
      pretibial myxedema, classically presents as nonpitting edema or plaquelike
      lesions on the pretibial region, while thyroid acropachy (TA) is seen in cases of
      severe TD, characterized by soft tissue swelling and clubbing of fingers and
      toes, as well as a periosteal reaction of the bones of the hands and feet. Both
      TD and TA are rare manifestations of thyroid disease and uncommonly reported in
      pediatric patients. Our aim was to increase awareness of dermatological
      manifestations associated with pediatric GD and review the literature of
      pediatric thyroid dermopathy as well as report a case of acropachy in a child.

PMID- 30187964
TI  - Management of a rare presentation of Kindler disease with digital constriction
      bands-Case report.
AB  - Kindler disease is a type of epidermolysis bullosa associated with acral
      blistering, diffuse cutaneous atrophy, poikiloderma, mucosal stenosis, and
      photosensitivity. This is the first case report in the literature to describe
      constriction bands associated with Kindler disease causing ischemia of the
      fingertips requiring urgent release and full-thickness skin grafts.
      Dermatologists reviewing such patients need to be aware of this condition and
      refer to a children's hand surgeon early to avoid leaving patients with prolonged
      periods of pain.

PMID- 30187963
TI  - Neonatal urticaria: Could it be CAPS?
AB  - A neonatal boy presented with a persistent urticarial rash. Initial
      investigations showed raised inflammatory markers and evidence of systemic
      inflammation. A working diagnosis of cryopyrin-associated periodic syndrome
      (CAPS) was made, and the patient responded extremely well to Anakinra. Molecular
      genetic testing revealed a somatic mutation (affecting 12.5% of cells) in the
      NLRP3 gene, accounting for the persistent inflammatory state but milder phenotype
      as seen in our patient.

PMID- 30187965
TI  - LncRNA NBR2 inhibits epithelial-mesenchymal transition by regulating Notch1
      signaling in osteosarcoma cells.
AB  - Long noncoding RNAs (lncRNAs) have been identified to have increasingly important
      roles in tumorigenesis, and they may serve as novel biomarkers for cancer
      therapy. Recent studies have demonstrated that lncRNA NBR2 (neighbor of BRCA1
      gene 2), a novel identified lncRNA, is decreased in several cancers; however, the
      role of NBR2 in the development of osteosarcoma has not been elucidated. In our
      study, we found that NBR2 expression was downregulated in osteosarcoma tissues,
      and osteosarcoma cases with lower NBR2 expression exhibited a shorter overall
      survival time compared with those with higher NBR2 expression. NBR2
      overexpression inhibited osteosarcoma cell proliferation, invasion, and migration
      but did not increase apoptosis. Furthermore, RNA-binding protein
      immunoprecipitation assays confirmed that NBR2 directly binds to Notch1 protein.
      Furthermore, overexpression of Notch1 in NBR2-overexpressing osteosarcoma cells
      reversed the effects of NBR2 on cell proliferation, invasion, migration, and
      epithelial-mesenchymal transition. The in vivo results showed that NBR2
      overexpression inhibited tumor growth in nude mice that were inoculated with
      osteosarcoma cells. NBR2 overexpression also suppressed the messenger RNA (mRNA)
      expression of Notch1, N-cadherin, and vimentin and increased the mRNA expression
      of E-cadherin in the tumor tissues. These data indicated that NBR2 served as a
      tumor suppressor gene in osteosarcoma and inhibited osteosarcoma cell
      proliferation, invasion, and migration. The current study provides a novel
      insight and treatment strategy for osteosarcoma.

PMID- 30187966
TI  - Midurethral support is also necessary for reflex closure of the urethra.
AB  - BACKGROUND AND OBJECTIVES: The pathophysiology of female stress urinary
      incontinence (SUI) is far from unraveled. Capturing all aspects of this
      bothersome condition in one theory remains challenging. The well-known Hammock
      and Integral theories, both from the early 90's, were successful in explaining a
      large proportion of the observations made in clinical practice. Nevertheless,
      some (pre)clinical observations cannot be explained by the current understanding.
      One of the issues concerns the pressure transmission. Is this process really a
      passive mechanical action, or is an additional active mechanism responsible for
      urethral closure? The finding that an increase in urethral pressure sometimes
      precedes and exceeds the increase in intravesical pressure suggests the latter.
      This concept has never been incorporated in one of the existing theories
      describing SUI. This is remarkable as a lot of evidence has been generated in
      recent years that proves involvement of active components. This review aims to
      provide an additional theory in which an active reflex closure mechanism of the
      urethra is incorporated. METHODS: Recent as well as older publications from
      clinical and animal studies are included to support the hypothesis. RESULTS: The
      smooth muscles of the urethra, the vascular bed, and the estrogen-influenced
      urethral mucosa, combined with striated muscle tone, contribute to the intra
      urethral pressure. A passive transmission of force to the urethra exists only in
      the abdominal proximal third of the urethra. In the distal two thirds of the
      urethra an active closure mechanism is present, dependent on sufficient urethral
      support in the proper anatomical position. This active closure mechanism is
      generated by reflex contraction of striated muscles of the urethra and the pelvic
      floor. CONCLUSION: Continence is a result of passive as well as active urethral
      closure mechanisms. The most important factor in female continence seems to be
      the proper functioning of an active reflex urethral closing mechanism.

PMID- 30187967
TI  - Temporal trends in prenatal risk factors for the development of infantile
      hemangiomas.
AB  - BACKGROUND/OBJECTIVES: Specific maternal risk factors have recently been
      identified in the development of infantile hemangiomas (IH), including
      gestational diabetes (GDM), maternal antihypertensive medication use or
      gestational hypertension (GHTN), maternal progesterone use, and artificial
      reproductive technologies (ART). We sought to explore the change in incidence of
      these risk factors over time and determine their association with the increased
      incidence of hemangiomas over 35 years, as previously reported. METHODS: The
      charts of 869 mother and infant pairs (infants previously diagnosed with IH
      between January 1, 1976, and December 31, 2010) were reviewed for prenatal
      complications. Rates of the prenatal complications over the 35-year period in
      birth mothers of infants diagnosed with IH were determined and evaluated by year
      of diagnosis (1976-1990, 1991-2000, and 2001-2010). RESULTS: Over the 35-year
      period in which the incidence of IH was previously examined, maternal age at
      delivery, prepregnancy body mass index (BMI), use of ART, maternal progesterone
      use, placental abnormalities, and GDM also increased. CONCLUSIONS: GDM, ART, and
      maternal progesterone use increased over the past 35 years, mirroring the
      previously reported trend of increasing incidence of IH. Maternal age and BMI
      also increased in mothers of infants with IH. Further exploration of this
      association may direct future research in the pathogenesis of infantile
      hemangiomas.

PMID- 30187968
TI  - Quercetin-mediated regulation of signal transduction cascades and microRNAs:
      Natural weapon against cancer.
AB  - Recent technological and analytical breakthroughs in genomics and proteomics have
      deepened our understanding related to the multifaceted nature of cancer. Because
      of therapeutically challenging nature of cancer, there has been a renewed
      interest in phytochemistry, and much attention is currently being given to the
      identification of signaling pathway inhibitors. Data obtained through high
      throughput technologies has provided a broader landscape of wiring maps of
      complex oncogenic signaling networks, thus revealing novel therapeutic
      opportunities. Increasingly, it is being realized that although our knowledge
      related to physiological and pathophysiological roles of signal transduction
      cascades has evolved rapidly, the clinical development of signaling pathway
      inhibitors has been challenging. Quercetin has attracted considerable attention
      because of its amazingly high pharmacological value. Research over decades has
      sequentially shown that quercetin effectively inhibited cancer development and
      progression. In this review, we have attempted to set the spotlight on the
      regulation of different cell signaling pathways by quercetin. We partition this
      multicomponent review into how quercetin effectively regulates the Wnt/beta
      catenin pathway, Janus kinase-signal transducer and activator of transcription
      pathway, and vascular endothelial growth factor/vascular endothelial growth
      factor receptor signaling cascade in different types of cancers. We also provide
      an overview of the regulation of NOTCH and SHH pathways by quercetin. MicroRNAs
      (miRNAs) have also emerged as versatile regulators of cancer, and contemporary
      studies have shed light on the ability of quercetin to control different miRNAs
      in various cancers. We have scattered information related to NOTCH and SHH
      pathways, and future studies must converge on the investigation of these pathways
      to see how quercetin modulates the signaling machinery of these pathways.

PMID- 30187969
TI  - A comparative study of obstetric anal sphincter injuries in vaginal deliveries of
      twins and singleton pregnancies.
AB  - AIMS: Increasing numbers of twin pregnancies necessitate investigation of the
      risk factors associated with obstetric anal sphincter injuries (OASIS). The aims
      of this study were to establish the incidence of OASIS, and compare women
      delivering twins to those delivering singletons in risk of OASIS plus maternal,
      neonatal, and obstetric outcomes. METHODS: A retrospective cohort study was
      undertaken and included women delivering in a tertiary London maternity unit
      between 1999 and 2015; 51 957 eligible women with singleton and 261 with twin
      pregnancies were identified. Women delivering twins were compared to those
      delivering singletons in the occurrence of maternal, neonatal, and obstetric
      outcomes using unadjusted relative risks. A secondary analysis was performed, and
      conditional logistic regression used to derive an adjusted relative risk of
      OASIS. Women delivering singletons were matched to those delivering twins for
      age, parity, ethnicity, gestation, and mode of delivery in a ratio of 2:1.
      RESULTS: Compared to the singleton group, mothers delivering twins had
      significantly more instrumental deliveries (RR [95%CI] 1.92 [1.67-2.27]; P <
      0.0001), smaller fetuses (2754.1 vs 3383.8 g; P < 0.001), and were older (32.9 vs
      31.0 years; P < 0.0001). The twin group was not significantly different to the
      singleton group in risk of OASIS (RR 0.61 [0.27-1.33], P = 0.205). The
      conditional logistic regression demonstrated similar results for the risk of
      OASIS (adjusted RR = 0.58 [0.22-1.47]; P = 0.253). CONCLUSIONS: Women delivering
      twins vaginally were not at a significantly higher risk of sustaining OASIS
      compared to those delivering singletons.

PMID- 30187970
TI  - Trimethoprim-sulfamethoxazole-induced drug reaction with eosinophilia and
      systemic symptoms in a child with congenital renal disease.
AB  - We present a special case of an 8-year-old girl diagnosed with severe drug
      reaction with eosinophilia and systemic symptoms due to trimethoprim
      sulfamethoxazole for urinary tract infection prophylaxis for congenital
      vesicoureteral reflux. The patient is believed to have developed drug reaction
      with eosinophilia and systemic symptoms because of her underlying renal disease.

PMID- 30187972
TI  - The Role of Graphene and Other 2D Materials in Solar Photovoltaics.
AB  - 2D materials have attracted considerable attention due to their exciting optical
      and electronic properties, and demonstrate immense potential for next-generation
      solar cells and other optoelectronic devices. With the scaling trends in
      photovoltaics moving toward thinner active materials, the atomically thin bodies
      and high flexibility of 2D materials make them the obvious choice for integration
      with future-generation photovoltaic technology. Not only can graphene, with its
      high transparency and conductivity, be used as the electrodes in solar cells, but
      also its ambipolar electrical transport enables it to serve as both the anode and
      the cathode. 2D materials beyond graphene, such as transition-metal
      dichalcogenides, are direct-bandgap semiconductors at the monolayer level, and
      they can be used as the active layer in ultrathin flexible solar cells. However,
      since no 2D material has been featured in the roadmap of standard photovoltaic
      technologies, a proper synergy is still lacking between the recently growing 2D
      community and the conventional solar community. A comprehensive review on the
      current state-of-the-art of 2D-materials-based solar photovoltaics is presented
      here so that the recent advances of 2D materials for solar cells can be employed
      for formulating the future roadmap of various photovoltaic technologies.

PMID- 30187971
TI  - Sonic hedgehog regulation of human rhabdosphincter muscle:Potential implications
      for treatment of stress urinary incontinence.
AB  - AIMS: Rhabdosphincter (RS) muscle injury occurs during prostatectomy, and is a
      leading cause of stress urinary incontinence (SUI). Current SUI treatments
      engender significant side effects, which negatively impact patient quality of
      life. Thus an unmet need exists to develop novel RS regeneration methods. We have
      shown that Sonic hedgehog (SHH) is a critical regulator of penile smooth muscle,
      and we have developed novel peptide amphiphile nanofiber hydrogel delivery of SHH
      protein to the penis to regenerate smooth muscle after prostatectomy induced
      injury. If similar SHH signaling mechanisms regulate RS muscle homeostasis, this
      innovative technology may be adapted for RS regeneration post-prostatectomy. We
      examine the SHH pathway in human RS muscle. METHODS: Human RS obtained during
      radical cystoprostatectomy (n = 13), underwent SHH pathway analysis. Primary
      cultures were established (n = 5), and RS cells were treated with SHH protein,
      SHH inhibitor, or PBS (control). Immunohistochemical analysis for SHH pathway,
      skeletal muscle actin, and trichrome stain were performed. RS growth was
      quantified at 3 and 6 days. RESULTS: SHH, it is receptors patched and smoothened,
      and transcriptional activators, GLI proteins, were identified in human RS muscle.
      At 3 and 6 days, RS cells increased 62% and 78% (P = 0.0001) with SHH treatment
      and decreased 40% (P = 0.0001) and 18% (P = 0.039) with SHH inhibition.
      CONCLUSIONS: The SHH pathway was identified in human RS. RS growth increased with
      SHH treatment, indicating intervention may be possible to enhance RS
      regeneration, and impact SUI. Peptide amphiphile delivery of SHH may be
      applicable for RS regeneration and SUI prevention.

PMID- 30187973
TI  - Bioorthogonal Uncaging of the Active Metabolite of Irinotecan by Palladium
      Functionalized Microdevices.
AB  - SN-38, the active metabolite of irinotecan, is released upon liver hydrolysis to
      mediate potent antitumor activity. Systemic exposure to SN-38, however, also
      leads to serious side effects. To reduce systemic toxicity by controlling where
      and when SN-38 is generated, a new prodrug was specifically designed to be
      metabolically stable and undergo rapid palladium-mediated activation. Blocking
      the phenolic OH of SN-38 with a 2,6-bis(propargyloxy)benzyl group led to
      significant reduction of cytotoxic activity (up to 44-fold). Anticancer
      properties were swiftly restored in the presence of heterogeneous palladium (Pd)
      catalysts to kill colorectal cancer and glioma cells, proving the efficacy of
      this novel masking strategy for aromatic hydroxyls. Combination with a Pd
      activated 5FU prodrug augmented the antiproliferative potency of the treatment,
      while displaying no activity in the absence of the Pd source, which illustrates
      the benefit of achieving controlled release of multiple approved therapeutics
      sequentially or simultaneously-by the same bioorthogonal catalyst to increase
      anticancer activity.

PMID- 30187974
TI  - The Physics of Light Emission in Halide Perovskite Devices.
AB  - Light emission is a critical property that must be maximized and controlled to
      reach the performance limits in optoelectronic devices such as photovoltaic solar
      cells and light-emitting diodes. Halide perovskites are an exciting family of
      materials for these applications owing to uniquely promising attributes that
      favor strong luminescence in device structures. Herein, the current understanding
      of the physics of light emission in state-of-the-art metal-halide perovskite
      devices is presented. Photon generation and management, and how these can be
      further exploited in device structures, are discussed. Key processes involved in
      photoluminescence and electroluminescence in devices as well as recent efforts to
      reduce nonradiative losses in neat films and interfaces are discussed. Finally,
      pathways toward reaching device efficiency limits and how the unique properties
      of perovskites provide a tremendous opportunity to significantly disrupt both the
      power generation and lighting industries are outlined.

PMID- 30187975
TI  - Low-grade squamous intraepithelial lesion, cannot rule out high-grade lesion:
      Diagnosis, histological outcomes and human papillomavirus results.
AB  - BACKGROUND: The 2014 Bethesda System for Reporting Cervical Cytology classifies
      squamous intraepithelial lesions (SILs) of cervix into two main categories: low
      grade SIL (LSIL) and high-grade SIL (HSIL). In some clinical practices, the LSIL
      cannot rule out high-grade lesion (LROH) interpretive category is used in cases
      with LSIL and findings that may raise the possibility of HSIL. Our purpose is to
      assess follow-up histopathology and high-risk human papillomavirus (hrHPV)
      results in patients with LROH, in comparison with LSIL, atypical squamous cells,
      cannot rule out HSIL (ASC-H), and HSIL in our institution. DESIGN: Cervical
      Papanicolaou tests with LROH, LSIL, ASC-H and HSIL interpretation, surgical
      follow-up, and hrHPV status were retrieved from the computer database from May
      2014 to December 2016. RESULTS: Of 109 963 total Papanicolaou tests, LROH
      comprised 0.3%, LSIL 3.1%, ASC-H 0.2% and HSIL 0.4%. Only 3272 cases with
      surgical diagnoses were included in the study. The most common histological
      outcome for ASC-H was cervical intraepithelial neoplasia (CIN)2/3 (32.6%); LSIL
      was CIN 1 (45.7%); LROH was CIN 1 (46.7%) and HSIL was CIN 2/3 (64.4%). For LROH
      and LSIL, 31.1% and 7.5% respectively, had CIN 2/3. Approximately 79% of cases
      were hrHPV positive. Of LROH cases with surgical follow-up, 86.9% tested hrHPV
      positive, accounting for the second most common positive group after HSIL
      (92.6%). CONCLUSION: In our study cohort, LROH interpretation is associated with
      a higher number of CIN 2 or higher lesions on follow-up compared to patients with
      LSIL (P < 0.0001), and is associated with a significant percentage of positive
      other hrHPV, supporting LROH as a useful diagnostic category that triggers
      appropriate follow-up in affected women.

PMID- 30187977
TI  - Internet health scams-Developing a taxonomy and risk-of-deception assessment
      tool.
AB  - The prevalence of health scams in Canada is increasing, facilitated by the rise
      of the Internet. However, little is known about the nature of this phenomena.
      This study sought to methodically identify and categorise Internet-based Health
      Scams (IHS) currently active in Canada, creating an initial taxonomy based on
      systematic Internet searches. A five-step Delphi approach, comprised of a
      multidisciplinary panel of health professionals from the University of British
      Columbia, in Vancouver, Canada, was used to establish consensus. The resulting
      taxonomy is the first to characterise the nature of IHS in North America. Five
      core areas of activity were identified: body image products, medical products,
      alternative health services, healthy lifestyle products, and diagnostic testing
      services. IHS purveyors relied on social expectations and psychological
      persuasion techniques to target consumers. Persuasion techniques included social
      engagement, claims of miraculous effects, scarcity, and the use of
      pseudoscientific language. These techniques exploited personality traits of
      sensation seeking, needing self-control, openness to taking risks, and the
      preference for uniqueness. The data gathered from the taxonomy allowed the Delphi
      panel to develop and pilot a simple risk-of-deception tool. This tool is intended
      to help healthcare professionals educate the public about IHS. It is suggested
      that, where relevant, healthcare professionals include a general discussion of
      IHS risks and marketing techniques with clients as a part of health promotion
      activities.

PMID- 30187976
TI  - Bacteriology and clinical outcomes of patients with culture-positive pleural
      infection in Western Australia: A 6-year analysis.
AB  - BACKGROUND AND OBJECTIVE: Pleural infection is a clinical challenge; its
      microbiology can be complex. Epidemiological and outcome data of pleural
      infection in adult Australians are lacking. We describe the bacteriology and
      clinical outcomes of Australian adults with culture-positive pleural infection
      (CPPI) over a 6-year period. METHODS: Cases with CPPI were identified through
      Western Australian public hospitals electronic record. Culture isolates,
      admission dates, vital status, co-morbidities, radiology, blood and pleural fluid
      tests were extracted. RESULTS: In total, 601 cases (71.4% males; median age: 63
      years (IQR: 50-74); median hospital stay 13 days) involving 894 bacterial
      isolates were identified. Hospital-acquired (HA)-CPPI was defined in 398 (66.2%)
      cases, community-acquired (CA)-CPPI in 164 (27.3%) cases and the remaining
      classified as oesophageal rupture/leak. Co-morbidities, most frequently cancer,
      were common (65.2%). Radiological evidence of pneumonia was present in only 43.8%
      of CA-CPPI and 27.3% of HA-CPPI. Of the 153 different bacterial strains cultured,
      Streptococcus species (32.9%) especially viridans streptococci group were most
      common in CA-CPPI, whereas HA-CPPI was most often associated with Staphylococcus
      aureus (11.6%) and Gram-negative (31.9%) infections. Mortality was high during
      hospitalization (CA-CPPI 13.4% vs HA-CPPI 16.6%; P = 0.417) and at 1 year (CA
      CPPI 32.4% vs HA-CPPI 45.5%; P = 0.006). CONCLUSION: This is the first large
      multicentre epidemiological study of pleural infection in Australian adults and
      includes the largest cohort of HA-CPPI published to date. CPPI is caused by a
      diverse range of organisms which vary between CA and HA sources. CPPI is a poor
      prognostic indicator both in the short term and in the subsequent 12 months.

PMID- 30187978
TI  - Varenicline versus placebo for waterpipe smoking cessation: a double-blind
      randomized controlled trial.
AB  - BACKGROUND AND AIMS: Waterpipe tobacco smoking is a growing public health
      concern. There is limited research using pharmacotherapy and no research using
      varenicline (established treatment for smoking cessation) in waterpipe smokers.
      We tested the efficacy of varenicline in achieving abstinence from all tobacco
      use among waterpipe smokers. DESIGN: Two-arm, parallel group, placebo-controlled,
      double-blind, multi-centre (n = 4), individually randomized trial with follow-up
      to 25 weeks. SETTINGS: District general hospitals and catchment communities
      within four districts of Punjab, Pakistan. PARTICIPANTS: Adult daily waterpipe
      smokers (n = 510; 253 in varenicline and 257 in placebo arms), who were
      interested in quitting, were recruited and analysed between March and November
      2016. Of these, 220 (87%) in the varenicline and 239 (93%) in the placebo arms
      completed all follow-ups. Participants were on average aged 49 [standard
      deviation (SD) = 15.2] years, daily smokers and smoked for the last 27 (SD =
      15.9) years. More than half (261, 51.2%) also smoked cigarettes. INTERVENTION AND
      COMPARATOR: All trial participants received two structured sessions of
      behavioural support (of 30 and 10 minutes) one at the time of registration and
      the other 1 week later. Participants were randomized to varenicline (active arm)
      and placebo (control arm) stratified on district, sex and concomitant cigarette
      smoking. Varenicline and placebo were dispensed as identical unlabelled tablets
      for 12 weeks: 0.5 mg for 1 week (once on days 1-3, twice on days 4-7) and 1 mg
      for the subsequent 11 weeks (twice daily). MEASUREMENTS: The trial participants
      were followed-up for a period of 25 weeks post-randomization. The primary outcome
      was 7-day repeated point prevalence abstinence from all forms of tobacco, self
      reported at each of weeks 5, 12 and 25, verified by carbon-monoxide cut-off < 10
      parts per million. FINDINGS: No evidence of statistically significant difference
      in repeated point prevalence abstinence between the varenicline (12 of 253; 4.7%)
      and placebo (11 of 257; 4.3%) arms (relative risk = 1.11, 95% confidence interval
      = 0.50-2.47, P = 0.80) was observed (Bayes factor = 0.048). Adverse events
      reported in 27 participants were 34 (15 in varenicline and 19 in placebo); none
      was serious. CONCLUSIONS: Varenicline was not more effective than placebo in
      aiding cessation of tobacco use in long-term daily waterpipe smokers.

PMID- 30187979
TI  - No measurable fitness cost to experimentally evolved host defence in the
      Caenorhabditis elegans-Serratia marcescens host-parasite system.
AB  - Host susceptibility to parasites can vary over space and time. Costs associated
      with the maintenance of host defence are thought to account for a portion of this
      variation. Specifically, trade-offs wherein elevated defence is maintained at the
      cost of fitness in the absence of the parasite may cause levels of host defence
      to change over time and differ between populations. In previous studies, we found
      that populations of the host nematode, Caenorhabditis elegans, evolved greater
      levels of parasite avoidance and resistance against the bacterial parasite,
      Serratia marcescens. Here, we passaged these host populations either in the
      presence or absence of the parasite to test for a cost of elevated host defences.
      After 16 generations, we found that elevated levels of host defence were
      maintained during evolution in both the presence and absence of the parasite.
      Further, this maintenance of defence was not the result of limited standing
      genetic variation, but rather the absence of a measurable cost associated with
      defence. Therefore, costs associated with host defence may not broadly account
      for differences in host susceptibility across space and time.

PMID- 30187981
TI  - The effect of nonsurgical periodontal treatment on gingival crevicular fluid
      stress hormone levels: A prospective study.
AB  - OBJECTIVES: The purpose of this prospective study was to investigate the effect
      of nonsurgical periodontal treatment (PT) on anxiety/depression scale scores and
      on gingival crevicular fluid (GCF) cortisol (COR) and dehydroepiandrosterone
      (DHEA) levels. METHODS: Fifty-five participants with generalized chronic
      periodontitis (GCP group, n: 21), with localized chronic periodontitis (LCP
      group, n: 19) and with gingivitis or healthy (control group, n: 15) subjects were
      treated and followed up for 6 months. Clinical periodontal parameters include
      plaque index, gingival index, bleeding on probing, probing depth and attachment
      level; psychosocial measurements include Beck Depression Inventory (BDI) and
      State-Trait Anxiety Inventory (STAI 1-2) psychometric instruments; hormone levels
      in GCF including COR and DHEA were evaluated. RESULTS: All clinical parameters
      were significantly decreased (except attachment loss) after PT (p < 0.05). No
      significant differences were observed between the two groups for STAI-1-2 and BDI
      scores, either at baseline or at 6 months (p > 0.05). COR levels were
      statistically lower following PT in GCP and LCP groups when compared to the
      baseline levels (p < 0.05). DHEA values at baseline and 6 months did not show
      significant differences. CONCLUSION: Within the limits of the study, decreased
      GCF COR and unchanged GCF DHEA levels were determined in nonsurgically treated
      patients regardless of the extent and severity of periodontitis.

PMID- 30187982
TI  - You never walk alone: An exploratory study of the needs and burden of an informal
      care group.
AB  - Little is known about the dynamics of a group of people giving informal care
      together. The aim of this study was to investigate the characteristics of an
      informal care group, the obstacles the informal care group experiences, the needs
      and desires they have and how the informal care group can be supported by general
      practitioners (GPs) and other professionals. Nine informal care groups were
      interviewed based on a questionnaire that was preapproved by the six Flemish
      official informal caregiver organisations. The results were analysed using open
      coding. A survey was conducted among 137 caregivers who were part of a group.
      Univariate analysis was performed. Informal care group usually consist of close
      relatives of the patient, with often the partner of the patient as the main
      caregiver. The size of the informal care group depends on the size of the family.
      If there are more caregivers in a group, the perceived burden of the individual
      caregiver decreases. The support of the other caregivers in the group increases
      capacity. The cooperation and agreements are often spontaneously organised and
      few problems are reported. There is a large variation in the expectations of
      support from the general practitioner, ranging from availability in emergencies
      to information about the possibilities of formal home care. This study depicts a
      positive image of the informal care group. Being part of a caregiver group both
      decreases burden and increases capacity. Informal care groups usually function
      well without a need for formal agreements within the group, and they rarely need
      a third party to coordinate with them or intervene.

PMID- 30187980
TI  - A comparison of genomic islands of differentiation across three young avian
      species pairs.
AB  - Detailed evaluations of genomic variation between sister species often reveal
      distinct chromosomal regions of high relative differentiation (i.e., "islands of
      differentiation" in FST ), but there is much debate regarding the causes of this
      pattern. We briefly review the prominent models of genomic islands of
      differentiation and compare patterns of genomic differentiation in three closely
      related pairs of New World warblers with the goal of evaluating support for the
      four models. Each pair (MacGillivray's/mourning warblers; Townsend's/black
      throated green warblers; and Audubon's/myrtle warblers) consists of forms that
      were likely separated in western and eastern North American refugia during cycles
      of Pleistocene glaciations and have now come into contact in western Canada,
      where each forms a narrow hybrid zone. We show strong differences between pairs
      in their patterns of genomic heterogeneity in FST , suggesting differing
      selective forces and/or differing genomic responses to similar selective forces
      among the three pairs. Across most of the genome, levels of within-group
      nucleotide diversity (piWithin ) are almost as large as levels of between-group
      nucleotide distance (piBetween ) within each pair, suggesting recent common
      ancestry and/or gene flow. In two pairs, a pattern of the FST peaks having low
      piBetween suggests that selective sweeps spread between geographically
      differentiated groups, followed by local differentiation. This "sweep-before
      differentiation" model is consistent with signatures of gene flow within the
      yellow-rumped warbler species complex. These findings add to our growing
      understanding of speciation as a complex process that can involve phases of
      adaptive introgression among partially differentiated populations.

PMID- 30187983
TI  - Histochemistry of the zona pellucida of the ovary of a species with natural
      polyovulation: Lagostomus maximus (Rodentia, Hystricomorpha, Chinchillidae).
AB  - This study reports the histochemistry and the distribution of glycoconjugates
      (GCs) in the zona pellucida (ZP) of preantral, secondary, tertiary, polyovulatory
      and atretic follicles of ovaries from non-pregnant (NPr) and pregnant (Pr)
      females of Lagostomus maximus. GCs were studied using histochemical and lectin
      histochemical methods. The viscacha ZP was positive to all the histochemical
      techniques. In addition, it was observed that the intensity of staining of the ZP
      was constant in the different follicular stages between both female groups. The
      lectin histochemical study revealed that ZP was positive for certain lectins
      (WGA, RCA-I and CON-A) and that the labelling did not vary between the different
      follicular stages, but between the two groups of females. By using both
      histochemical techniques, it was established that the GCs present in the ZP label
      the complexity of the area. These results allow us to increase our knowledge on
      the biology of the viscacha's ovary, particularly contributing to the study of
      polyovulation.

PMID- 30187984
TI  - Bridging silos: Delivering integrated care to patients with cancer in Ontario,
      Canada.

PMID- 30187985
TI  - New advances in the molecular classification of pediatric mesenchymal tumors.
AB  - Pediatric soft tissue tumors are relatively rare and show significant overlap in
      morphology and immunoprofile, often posing diagnostic and management challenges.
      Thus, their classification remains often subjective or lumped under "unclassified
      categories," as a number of lesions lack objective and reproducible criteria in
      diagnosis. Although in a subset of cases immunohistochemistry has been proved
      useful to identify a specific line of differentiation, most tumors lack a readily
      defined histogenesis, being characterized by a rather non-specific immunoprofile.
      Furthermore, tumors with an ambiguous diagnosis are difficult to grade and their
      risk of malignancy or clinical management remains uncertain. Advances in
      molecular genetics, including the more wide application of next generation
      sequencing in routine clinical practice, have improved diagnosis and refined
      classification based on objective molecular markers. Importantly, some soft
      tissue tumors in children are characterized by recurrent gene fusions involving
      either growth factors (eg, PDGFB) or protein kinases (eg, ALK, ROS, NTRK, BRAF),
      which have paved the way for new targeted treatments that block the respective
      upregulated downstream pathways. However, the majority of gene fusions or
      mutations detected in soft tissue tumors result in an abnormal function of
      transcription factors or chromatin remodeling. The present review focuses on the
      latest genetic discoveries in the spectrum of both benign and malignant pediatric
      soft tissue neoplasia. These genetic abnormalities promise to provide relevant
      insight for their proper classification, prognosis, and treatment. The entities
      discussed herein are grouped either based on their shared genetic mechanism or
      based on their presumed line of differentiation.

PMID- 30187986
TI  - Methionine is required for cAMP-PKA mediated morphogenesis and virulence of
      Candida albicans.

PMID- 30187987
TI  - Host-derived population genomics data provides insights into bacterial and diatom
      composition of the killer whale skin.
AB  - Recent exploration into the interactions and relationship between hosts and their
      microbiota has revealed a connection between many aspects of the host's biology,
      health and associated micro-organisms. Whereas amplicon sequencing has
      traditionally been used to characterize the microbiome, the increasing number of
      published population genomics data sets offers an underexploited opportunity to
      study microbial profiles from the host shotgun sequencing data. Here, we use
      sequence data originally generated from killer whale Orcinus orca skin biopsies
      for population genomics, to characterize the skin microbiome and investigate how
      host social and geographical factors influence the microbial community
      composition. Having identified 845 microbial taxa from 2.4 million reads that did
      not map to the killer whale reference genome, we found that both ecotypic and
      geographical factors influence community composition of killer whale skin
      microbiomes. Furthermore, we uncovered key taxa that drive the microbiome
      community composition and showed that they are embedded in unique networks, one
      of which is tentatively linked to diatom presence and poor skin condition.
      Community composition differed between Antarctic killer whales with and without
      diatom coverage, suggesting that the previously reported episodic migrations of
      Antarctic killer whales to warmer waters associated with skin turnover may
      control the effects of potentially pathogenic bacteria such as Tenacibaculum
      dicentrarchi. Our work demonstrates the feasibility of microbiome studies from
      host shotgun sequencing data and highlights the importance of metagenomics in
      understanding the relationship between host and microbial ecology.

PMID- 30187988
TI  - Diradical Character Enhancement by Spacing: N-Heterocyclic Carbene Analogues of
      Muller's Hydrocarbon.
AB  - Two-fold C-C cross-coupling of N-heterocyclic carbenes [NHCs; SIPr=C(NArCH2 )2 ,
      1; IPr=C(NArCH)2 , 2; Me-IPr=C(NArCMe)2 , 3; Ar=2,6-iPr2 C6 H3 ] with 4,4''
      diiodo-p-terphenyl under Ni catalysis furnished [(SIPr)(C6 H4 )3 (SIPr)](I)2 (4),
      [(IPr)(C6 H4 )3 (IPr)](I)2 (5), and [(Me-IPr)(C6 H4 )3 (Me-IPr)](I)2 (6). Two
      electron reduction of 4-6 with KC8 readily afforded NHC analogues of Muller's
      hydrocarbon (MH), [(SIPr)(C6 H4 )3 (SIPr)] (7), [(IPr)(C6 H4 )3 (IPr)] (8), and
      [(Me-IPr)(C6 H4 )3 (Me-IPr)] (9), respectively, as highly colored crystalline
      solids. Quantum chemical calculations suggested that the singlet ground state for
      7-9 possesses a vertical singlet-triplet energy gap DeltaES-T of -7.24 to -7.60
      kcal mol-1 , which is significantly lower compared to that of the NHC analogues
      of Thiele's (TH) and Chichibabin's (CH) (18-38 kcal mol-1 ) hydrocarbons.
      Importantly, the calculated diradical character (y) of 7-9 (y~0.6) is
      considerably higher compared to that of the related TH and CH (y=0.1-0.4),
      suggesting the open-shell singlet character of 7-9.

PMID- 30187989
TI  - Venom gland size and venom complexity-essential trophic adaptations of venomous
      predators: A case study using spiders.
AB  - Specialized predators possess a variety of adaptations. In venomous predators,
      this may include the size of the venom gland and venom composition. It is
      expected that due to different foraging strategies, predators with a wide trophic
      niche (generalists) should possess larger venom glands that contain more
      diversified components than predators with a narrow niche (specialists). We
      focused on spiders, as the most diversified group of venomous predators, in which
      a wide variety of trophic strategies have evolved. We conducted a comparative
      analysis using 40 spider species, in which we measured the size of their venom
      gland and venom complexity using proteome profiling methods. The species were
      classified into three trophic groups: generalists, facultative specialists and
      obligatory specialists. We found that the venom glands of generalists are larger
      than those of obligatory specialists, which is presumably due to more frequent
      prey capture by the former. The complexity of venom of peptides (2-15 kDa) and
      proteins (15-250 kDa) was more diverse in generalists than in specialists.
      Multivariate analysis of venom revealed significant differences among the three
      trophic categories only in the complexity of peptides. Our study thus shows that
      venom gland size and its content have taken different pathways during the
      evolution of different trophic strategies in spiders. Generalists evolved larger
      venom glands with more complex composition, whereas obligatory specialists
      possess smaller glands with less diverse chemical structures.

PMID- 30187991
TI  - THRIVEable work environments: A study of interplaying factors that enable novice
      nurses to thrive.
AB  - AIM: The purpose of this study was to gain an understanding of the impact of the
      interplay between workplace and developmental factors that enable and disable
      thriving within the first year of nursing practice. BACKGROUND: While much is
      known about the high attrition rates among new graduate nurses, little research
      has explored the impact of interplay between workplace stressors and
      developmental assets. METHOD: Through a basic qualitative study, eight novice
      nurses underwent three in-depth interviews. RESULTS: The interplay between
      workplace factors and development factors such as congruence and self-compassion
      had a significant impact on the participants' ability to effectively manage
      workplace stimuli. CONCLUSION: Those lacking developmentally were more likely to
      perceive workplace stimuli as threatening, which had a significant impact on the
      ability to self-actualize as a novice nurse. Therefore, the role of interplay is
      significant in determining why some merely survive versus those who thrive,
      despite similar work environments. IMPLICATIONS FOR NURSING MANAGEMENT: A greater
      understanding of the impact of the role of interplay will inform transition
      programs by enabling nurse leaders to cater to the unique needs of new graduates
      as they step over the threshold of professional practice.

PMID- 30187990
TI  - Support for Australian carers from community pharmacy: Insight into carer
      perspectives of a novel service.
AB  - The feasibility of an individualised carer support service delivered in community
      pharmacies was assessed from the perspective of carer participants using a pre
      post questionnaire and semistructured interviews. Eligible pharmacies were
      required to offer a medication management service relevant to carers and have a
      semiprivate space for conversations. Carers were required to self-identify as an
      unpaid support person for someone with a chronic condition or disability. Between
      September 2016 and March 2017, staff from 11 community pharmacies in South-East
      Queensland, Australia were trained, and provided with ongoing mentoring from a
      pharmacist and carer to support service implementation. Identification of carers
      and support to achieve a personal and care-giving goal were key features of the
      service. Questionnaires included the EQ-5D-3L, the Bakas Caregiving Outcomes
      Scale, and questions relating to goal achievement, carer roles, and
      responsibilities. Seven follow-up carer interviews were undertaken between March
      and May 2017 and analysed thematically. Pre-post questionnaires were available
      for 17 carers (one withdrew, two incomplete). Of the 29 goals set, 10 were
      achieved and 14 partially achieved. EQ-5D-3L scores were unchanged, while 7 of
      the 15 items comprising the Bakas score improved (p < 0.05). Carer service
      evaluation was generally favourable, and these two main interview themes were the
      impact of caring and pharmacy experience. The impact of caring, while variable,
      was significant. Pharmacy experiences were mostly positive and the opportunity
      for carers to further engage with pharmacy staff was appreciated. The service was
      feasible and initial reported benefits to carers may support further research
      potentially in terms of a larger controlled trial.

PMID- 30187992
TI  - Synthesis of 5-Hydroxy-3',4',7-trimethoxyflavone and Related Compounds and
      Elucidation of Their Reversal Effects on BCRP/ABCG2-Mediated Anticancer Drug
      Resistance.
AB  - 3',4',7-Trimethoxyflavone (TMF) has been reported to show a potent reversal
      effect on drug resistance mediated by breast cancer resistance protein (BCRP)/ATP
      binding cassette subfamily G member 2 (ABCG2). In this study, we designed and
      synthesized five derivatives with either a hydroxy group or a fluorine atom at C
      5 and several kinds of capping moiety at the C-7 hydroxy group, on the same 3',4'
      dimethoxy-substituted flavone skeleton. We subsequently evaluated the efficacies
      of these compounds against BCRP-expressing human leukaemia K562/BCRP cells.
      Reversal of drug resistance was expressed as the concentration of compound
      causing a twofold reduction in drug sensitivity (RI50 ). Of the synthesized
      compounds, the reversal effect of 5-hydroxy-3',4',7-trimethoxyflavone (HTMF, RI50
      7.2 nm) towards 7-ethyl-10-hydroxycamptothecin (SN-38) was stronger than that of
      TMF (RI50 18 nm). Fluoro-substituted 5-fluoro-3',4',7-trimethoxyflavone (FTMF,
      RI50 25 nm) and monoglycosylated 7-(beta-glucosyloxy)-5-hydroxy-3',4'
      dimethoxyflavone (GOHDMF, 91 nm) also exhibited reversal effects, whereas the di-
      and triglycoside derivatives did not. TMF, HTMF and FTMF at 0.01-10 MUm
      upregulated the K562/BCRP cellular accumulation of Hoechst 33342 nuclear staining
      dye. In addition, western blotting revealed that treatment of K562/BCRP cells
      with 0.1 MUm TMF, HTMF or FTMT suppressed the expression of BCRP. HTMF showed the
      strongest inhibition of BCRP-mediated efflux and suppression of BCRP expression
      of the three effective synthesized flavones.

PMID- 30187993
TI  - High-Density RNA Microarrays Synthesized In Situ by Photolithography.
AB  - While high-density DNA microarrays have been available for over three decades,
      the synthesis of equivalent RNA microarrays has proven intractable until now.
      Herein we describe the first in situ synthesis of mixed-based, high-density RNA
      microarrays using photolithography and light-sensitive RNA phosphoramidites. With
      coupling efficiencies comparable to those of DNA monomers, RNA oligonucleotides
      at least 30 nucleotides long can now efficiently be prepared using modified
      phosphoramidite chemistry. A two-step deprotection route unmasks the
      phosphodiester, the exocyclic amines and the 2' hydroxyl. Hybridization and
      enzymatic assays validate the quality and the identity of the surface-bound RNA.
      We show that high-density is feasible by synthesizing a complex RNA permutation
      library with 262144 unique sequences. We also introduce DNA/RNA chimeric
      microarrays and explore their applications by mapping the sequence specificity of
      RNase HII.

PMID- 30187994
TI  - Synergistic antimetastatic effect of cotreatment with licochalcone A and
      sorafenib on human hepatocellular carcinoma cells through the inactivation of
      MKK4/JNK and uPA expression.
AB  - To improve the clinical outcome of tumor chemotherapy, more effective combination
      treatments against tumor metastasis and recurrence are required. Licochalcone A
      (LicA) is the root of Glycyrrhiza inflata and has been reported to possess anti
      inflammatory, antimicrobial, and antitumor effects. Sorafenib (Sor), a
      multikinase inhibitor, is used to treat patients with solid tumors such as
      advanced hepatocellular carcinoma (HCC). However, the synergistic effects of LicA
      and Sor on the metastasis of human HCC cells have not been reported. We found
      that LicA and Sor did not have cytotoxic effects or arrest growth in human SK-Hep
      1 and Huh-7 cells. In addition, treatment with LicA or Sor alone inhibited
      migration and invasion in human SK-Hep-1 and Huh-7 HCC cells. Furthermore,
      cotreatment with LicA and Sor synergistically inhibited the migration and
      invasion of HCC cells and significantly inhibited uPA protein expression.
      Notably, cotreatment of LicA and Sor synergistically and significantly
      downregulated MKK4-JNK expression. Through tail vein injection in nude mice, the
      aforementioned cotreatment synergistically suppressed SK-Hep-1 cell-mediated lung
      metastasis. These findings first revealed the synergistic effects of LicA and Sor
      cotreatment against human HCC cells, further suggesting that beneficial effects
      on tumor regression could be confirmed through prospective clinical trials.

PMID- 30187995
TI  - Reversible Photoswitching and Isomer-Dependent Diffusion of Single Azobenzene
      Tetramers on a Metal Surface.
AB  - Azobenzene is a prototypical molecular switch that can be reversibly
      photoisomerized between the nearly planar and apolar trans form, and the
      distorted, polar cis form. Most studies related to azobenzene derivatives have
      focused on planar adsorbed molecules. We present herein the study of a three
      dimensional shape-persistent molecular architecture consisting of four
      tetrahedrally arranged azobenzene units that is adsorbed on a Ag(111) surface.
      While the azobenzenes of the tripod in contact with the surface lost their
      switching ability, different isomers of the upright standing arm of the tetramer
      were obtained reversibly and efficiently by illumination at different
      wavelengths, revealing time constants of only a few minutes. Diffusion on the
      surface was dependent on the isomeric state-trans or cis-of the upright oriented
      azobenzene group. Hence, molecular mobility can be modulated by its isomeric
      state, which suggests that molecular growth processes could be controlled by
      external stimuli.

PMID- 30187996
TI  - Stiffening by Osmotic Swelling Constraint in Cartilage-Like Cell Culture
      Scaffolds.
AB  - Cartilage wounds result in chronic pain and degradation of the quality of life
      for millions of people. A synthetic cellular scaffold able to heal the damage by
      substituting the natural tissue is of great potential value. Here, it is shown
      for the first time that the unique interplay between the molecular components of
      cartilage can be reproduced in composite materials made of a polyelectrolyte
      hydrogel embedding a collagen scaffold. These composites possess a mechanical
      response determined by osmotic and electrostatic effects, comparable to articular
      cartilage in terms of elastic modulus, time-dependent response, and permeability
      to interstitial fluid flow. Made entirely from biocompatible materials, the
      cartilage-like composite materials developed permit 3D culture of chondrocyte
      like cells through their microporosity. The biomimetic materials presented here
      constitute an entirely new class of osmotically stiffened composites, which may
      find use outside of biomedical applications.

PMID- 30187997
TI  - Regarding the parallel opposed editorial about: 3D printing technology will
      eventually eliminate the need of purchasing commercial phantoms for clinical
      medical physics QA procedures.

PMID- 30187998
TI  - Correcting "insertion-deletion mutations" in medical terminology.

PMID- 30188000
TI  - Anticancer effects of high-dose ascorbate on canine melanoma cell lines.
AB  - The use of the well-known powerful antioxidant ascorbate has recently become more
      widespread in human medicine. Intravenous administration of high-dose ascorbate
      has been demonstrated to exert anticancer effects. It has resulted in effective
      cell death in vitro and inhibition of tumour growth in vivo. The aim of the
      current study was to evaluate the effects of high-dose ascorbate on canine
      melanoma in vitro. Four canine melanoma cell lines, UCDK9M1, UCDK9M3, UCDK9M4 and
      UCDK9M5 were treated with ascorbate for 2 hours at a range of millimolar
      concentrations (0-20 mM) to investigate the resulting effects on cell viability.
      All four canine melanoma cell lines exhibited reduced viability in a dose
      dependent manner. Further investigation demonstrated that high-dose ascorbate
      induced apoptosis via the activation of Bax. These findings suggest that high
      dose ascorbate has an anticancer effect on canine melanoma cell lines in vitro.
      With regard to clinical application, further in vivo investigation should be
      conducted.

PMID- 30187999
TI  - Plectin protects podocytes from adriamycin-induced apoptosis and F-actin
      cytoskeletal disruption through the integrin alpha6beta4/FAK/p38 MAPK pathway.
AB  - Podocyte injury is an early pathological change characteristic of various
      glomerular diseases, and apoptosis and F-actin cytoskeletal disruption are
      typical features of podocyte injury. In this study, we found that adriamycin
      (ADR) treatment resulted in typical podocyte injury and repressed plectin
      expression. Restoring plectin expression protected against ADR-induced podocyte
      injury whereas siRNA-mediated plectin silencing produced similar effects as ADR
      induced podocyte injury, suggesting that plectin plays a key role in preventing
      podocyte injury. Further analysis showed that plectin repression induced
      significant integrin alpha6beta4, focal adhesion kinase (FAK) and p38 MAPK
      phosphorylation. Mutating Y1494, a key tyrosine residue in the integrin beta4
      subunit, blocked FAK and p38 phosphorylation, thereby alleviating podocyte
      injury. Inhibitor studies demonstrated that FAK Y397 phosphorylation promoted p38
      activation, resulting in podocyte apoptosis and F-actin cytoskeletal disruption.
      In vivo studies showed that administration of ADR to rats resulted in
      significantly increased 24-hour urine protein levels along with decreased plectin
      expression and activated integrin alpha6beta4, FAK, and p38. Taken together,
      these findings indicated that plectin protects podocytes from ADR-induced
      apoptosis and F-actin cytoskeletal disruption by inhibiting integrin
      alpha6beta4/FAK/p38 pathway activation and that plectin may be a therapeutic
      target for podocyte injury-related glomerular diseases.

PMID- 30188001
TI  - Epithelial down-regulation of the miR-200 family in fibrostenosing Crohn's
      disease is associated with features of epithelial to mesenchymal transition.
AB  - Intestinal mesenchymal cells deposit extracellular matrix in fibrotic Crohn's
      disease (CD). The contribution of epithelial to mesenchymal transition (EMT) to
      the mesenchymal cell pool in CD fibrosis remains obscure. The miR-200 family
      regulates fibrosis-related EMT in organs other than the gut. E-cadherin,
      cytokeratin-18 and vimentin expression was assessed using immunohistochemistry on
      paired strictured (SCD) and non-strictured (NSCD) ileal CD resections and
      correlated with fibrosis grade. MiR-200 expression was measured in paired SCD and
      NSCD tissue compartments using laser capture microdissection and RT-qPCR. Serum
      miR-200 expression was also measured in healthy controls and CD patients with
      stricturing and non-stricturing phenotypes. Extra-epithelial cytokeratin-18
      staining and vimentin-positive epithelial staining were significantly greater in
      SCD samples (P = 0.04 and P = 0.03, respectively). Cytokeratin-18 staining
      correlated positively with subserosal fibrosis (P < 0.001). Four miR-200 family
      members were down-regulated in fresh SCD samples (miR-141, P = 0.002; miR-200a, P
      = 0.002; miR-200c, P = 0.001; miR-429; P = 0.004); miR-200 down-regulation in SCD
      tissue was localised to the epithelium (P = 0.001-0.015). The miR-200 target ZEB1
      was up-regulated in SCD samples (P = 0.035). No difference in serum expression
      between patient groups was observed. Together, these observations suggest the
      presence of EMT in CD strictures and implicate the miR-200 family as regulators.
      Functional studies to prove this relationship are now warranted.

PMID- 30188003
TI  - Preparation of Poly(lactic-co-glycolic acid)-Based Composite Microfibers for
      Postoperative Treatment of Tumor in NIR I and NIR II Biowindows.
AB  - In this work, a novel kind of electrospun microfiber to deliver a photothermal
      agent and an anticancer drug to tumor sites is explored. Photothermal therapy
      agent (MoS2 nanosheets) and doxorubicin (DOX) are incorporated with poly(lactic
      co-glycolic acid) (PLGA) microfiber via electrospinning a solution of PLGA, MoS2
      , and DOX. The designed microfiber with uniform fibrous morphology and negligible
      in vitro/in vivo hemo-/histo-toxicity is used as a durable photothermal agent,
      which shows an excellent photothermal transform ability and acceptable
      photothermal stability in both the first and second near-infrared light (NIR I
      and II) biowindows. The synergistic in vivo tumor chemotherapy and photothermal
      therapy efficiency of the composite microfibers are studied in postoperative
      treatment of cancer. It is found that the tumor postoperative reoccurrence can be
      completely prohibited owing to the synergistic tumor therapy efficiency in both
      the NIR I and NIR II biowindows.

PMID- 30188002
TI  - Prevalence of malocclusion in children with obstructive sleep apnoea.
AB  - OBJECTIVES: To describe the prevalence of malocclusions in 2- to 10-year-old
      children suffering from obstructive sleep apnoea (OSA) and to evaluate the
      association between occlusal variables and OSA. SETTING AND SAMPLE POPULATION: A
      total of 2101 consecutive patients referred to an otorhinolaryngology unit were
      considered for the study. One hundred and fifty-six children (range 2-10 years)
      with suspected OSA were selected for a sleep study. The final sample consisted of
      139 children suffering from OSA and a control group of 137 children. MATERIALS
      AND METHODS: All patients included in the study underwent a clinical orthodontic
      examination to record the following occlusal variables: primary canine
      relationship, presence of a posterior crossbite, overjet and overbite. Odds
      ratios and 95% confidence intervals, comparing the demographic characteristics
      and dental parameters in OSA vs non-OSA children, were computed. Multivariable
      logistic regression models were developed to compare independent variables
      associated with OSA to non-OSA children. RESULTS: The prevalence of malocclusions
      in children with OSA was 89.9% compared to 60.6% in the control group (P <
      0.001). Factors independently associated with OSA compared to the control group
      were posterior crossbite (OR = 3.38; 95%CI:1.73-6.58), reduced overbite (OR =
      2.43; 95%CI:1.15-5.15.), increased overbite (OR = 2.19; 95%CI:1.12-4.28) and
      increased overjet (OR = 4.25; 95%CI:1.90-9.48). CONCLUSIONS: This study showed a
      high prevalence of malocclusion in children with OSA compared to the control
      group. The posterior crossbite and deviations in overjet and overbite were
      significantly associated with OSA. The presence of these occlusal features shows
      the importance of an orthodontic evaluation in screening for paediatric OSA.

PMID- 30188004
TI  - Seeds of future past: climate change and the thermal memory of plant reproductive
      traits.
AB  - Plant persistence and migration in face of climate change depends on successful
      reproduction by seed, a central aspect of plant life that drives population
      dynamics, community assembly and species distributions. Plant reproduction by
      seed is a chain of physiological processes, the rates of which are a function of
      temperature, and can be modelled using thermal time models. Importantly, while
      seed reproduction responds to its instantaneous thermal environment, there is
      also evidence of phenotypic plasticity in response to the thermal history
      experienced by the plant's recent ancestors, by the reproducing plant since
      seedling establishment, and by its seeds both before and after their release.
      This phenotypic plasticity enables a thermal memory of plant reproduction, which
      allows individuals to acclimatise to their surroundings. This review synthesises
      current knowledge on the thermal memory of plant reproduction by seed, and
      highlights its importance for modelling approaches based on physiological thermal
      time. We performed a comprehensive search in the Web of Science and analysed 533
      relevant articles, of which 81 provided material for a meta-analysis of thermal
      memory in reproductive functional traits based on the effect size Zr. The
      articles encompassed the topics of seed development, seed yield (mass and
      number), seed dormancy (physiological, morphological and physical), germination,
      and seedling establishment. The results of the meta-analysis provide evidence for
      a thermal memory of seed yield, physiological dormancy and germination. Seed mass
      and physiological dormancy appear to be the central hubs of this memory. We argue
      for integrating thermal memory into a predictive framework based on physiological
      time modelling. This will provide a quantitative assessment of plant
      reproduction, a complex system that integrates past and present thermal inputs to
      achieve successful reproduction in changing environments. The effects of a
      warming environment on plant reproduction cannot be reduced to a qualitative
      interpretation of absolute positives and negatives. Rather, these effects need to
      be understood in terms of changing rates and thresholds for the physiological
      process that underlie reproduction by seed.

PMID- 30188005
TI  - Chemical evaluation and cytotoxic mechanism investigation of Clinacanthus nutans
      extract in lymphoma SUP-T1 cells.
AB  - Clinacanthus nutans has been used as herbal medicine with antidiabetic, blood
      pressure lowering, and diuretic properties in Singapore, Thailand, and Malaysia.
      The in vitro cellular study showed the chloroform extract possessed significant
      cytotoxicity against leukemia K562 and lymphoma Raji cells. The clinical study
      reported that administration of plant could treat or prevent relapse in 12 cancer
      patients. However, detailed mechanism of the anticancer effects and chemical
      profiles are not thoroughly studied. The chemical study did show that the acetone
      extract (MHA) exerted the highest antiproliferative effect on human leukemia MOLT
      4 cells and lymphoma SUP-T1 cells in dose-dependent cytotoxicity. We found that
      the use of MHA increased apoptosis by 4.28%-43.65% and caused disruption of
      mitochondrial membrane potential (MMP) by 11.79%-26.93%, increased reactive
      oxygen species (ROS) by 19.54% and increased calcium ion by 233.83%, as
      demonstrated by annexin-V/PI, JC-1, H2 DCFDA, and Flou-3 staining assays,
      respectively. MHA-induced ER stress was confirmed by increase expression of CHOP
      and IRE-1alpha with western blotting assay. In conclusion, we identified good
      bioactivity in Clinacanthus nutans and recognize its potential effect on cancer
      therapy, but further research is needed to determine the use of the plant.

PMID- 30188006
TI  - Detection and Evaluation of Anti-Cancer Efficiency of Astragalus Polysaccharide
      Via a Tissue Engineered Tumor Model.
AB  - Polysaccharides have been known to display their anti-cancer activity via
      immunomodulation. The immunomodulation of RAW 246.7 macrophages by astragalus
      polysaccharide (APS) is herein studied in human breast cancer cells. Apart from
      traditional 2D culture, a novel tissue-engineered tumor model is prepared based
      on decellularized porcine lung scaffold. Decellularized lung scaffolds exhibit
      preferable biocompatibility that promote the formation and enlargement of tumor
      spheroids. The conditioned medium (CM, the supernatant liquid of APS-treated
      RAW264.7 macrophages) shows anti-cancer activity by inhibiting cell
      proliferation, demonstrated by a 39.25 +/- 5.04% decrease in tumoroid size and
      20.96 +/- 2.43% reduction in cell viability, and promoting cell apoptosis by the
      nuclear fragmentation and increasing apoptotic-stage proportion. The cytotoxicity
      of CM is associated with the upregulated production of nitric oxide and tumor
      necrosis factor-alpha from RAW 246.7 cells stimulated by APS. Overall, by using
      this 3D tumor model to study CM, there is convincing evidence that APS can
      modulate macrophage function to further mediate anti-cancer activity.

PMID- 30188008
TI  - Diagnosis of dementia in residential aged care settings in Australia: An
      opportunity for improvements in quality of care?
AB  - OBJECTIVE: To examine the cognitive status of Australians living in residential
      aged care facilities (RACFs) and whether or not a dementia diagnosis was
      recorded. METHODS: Cross-sectional study of 541 residents of 17 RACFs spanning
      four states. Examination of cognitive status by Psychogeriatric Assessment Scale
      Cognitive Impairment Scale (PAS-Cog) and dementia diagnosis from medical records.
      RESULTS: The study population included 65% of residents with a diagnosis of
      dementia recorded, and 83% had a PAS-Cog score of four or more indicating likely
      cognitive impairment. More than 20% of participants had likely cognitive
      impairment (PAS-Cog >=4), but no diagnosis of dementia; 11% had moderate-to
      severe cognitive impairment (PAS-Cog >=10) but no recorded dementia diagnosis.
      CONCLUSION: There may be a lack of formal diagnosis of dementia in Australian
      RACFs. Greater efforts from all health professionals to improve diagnosis in this
      setting are required. This is an opportunity for improved person-centred care and
      quality of care in this vulnerable population.

PMID- 30188007
TI  - Parental age in relation to the severity of cleft lip and/or palate.
AB  - OBJECTIVE: To investigate parental age in relation to the severity of cleft
      diagnosis in a population-based consecutive sample of individuals with clefts.
      SETTING/SAMPLE: Retrospective, consecutive. MATERIAL/METHODS: The sample
      comprised 545 consecutive cases with nonsyndromic clefts (437 individuals with
      cleft lip with/without cleft palate [CL +/- P] and 106 individuals with isolated
      cleft palate [CP]) and parental ages recorded. The groups were subdivided
      according to the extent/severity of cleft. Unilateral clefts were divided
      according to left/right sidedness. Logistic regression was used to analyse the
      association between parental age and risk of severe cleft separately for CL +/- P
      and CP, as well as between parental age and risk of right-sided cleft. RESULTS:
      In CL +/- P, the risk of a complete cleft in the offspring increases with
      maternal age when the paternal age exceeds approximately 29 years. Moreover, the
      risk is higher when both parents are old than when both parents are young. In CP,
      no statistically significant results were identified. However, there were clear
      trends that indicated a similar pattern as that for CL +/- P. No association was
      identified between increased parental age and the sidedness of clefts.
      CONCLUSIONS: Parental age seems to contribute to cleft severity, as older parents
      showed a higher risk of having offspring with a complete cleft than younger
      parents.

PMID- 30188010
TI  - B-precursor acute lymphoblastic leukemia complicating 18q deletion syndrome.

PMID- 30188009
TI  - Equivalency of beam scan data collection using a 1D tank and automated couch
      movements to traditional 3D tank measurements.
AB  - This work shows the feasibility of collecting linear accelerator beam data using
      just a 1-D water tank and automated couch movements with the goal to maximize the
      cost effectiveness in resource-limited clinical settings. Two commissioning
      datasets were acquired: (a) using a standard of practice 3D water tank scanning
      system (3DS) and (b) using a novel technique to translate a commercial TG-51
      complaint 1D water tank via automated couch movements (1DS). The Extensible
      Markup Language (XML) was used to dynamically move the linear accelerator couch
      position (and thus the 1D tank) during radiation delivery for the acquisition of
      inline, crossline, and diagonal profiles. Both the 1DS and 3DS datasets were used
      to generate beam models (BM1 DS and BM3 DS ) in a commercial treatment planning
      system (TPS). 98.7% of 1DS measured points had a gamma value (2%/2 mm) < 1 when
      compared with the 3DS. Static jaw defined field and dynamic MLC field dose
      distribution comparisons for the TPS beam models BM1 DS and BM3 DS had 3D gamma
      values (2%/2 mm) < 1 for all 24,900,000 data points tested and >99.5% pass rate
      with gamma value (1%/1 mm) < 1. In conclusion, automated couch motions and a 1D
      scanning tank were used to collect commissioning beam data with accuracy
      comparable to traditionally acquired data using a 3D scanning system. TPS beam
      models generated directly from 1DS measured data were clinically equivalent to a
      model derived from 3DS data.

PMID- 30188011
TI  - HLA profile of the donors in the Macedonian Bone Marrow Donor Registry.
AB  - The importance of HLA alleles in the process of haematopoietic stem cell
      transplantation, especially the process of unrelated donor search, is enormous.
      Macedonian Bone Marrow Donor Registry was established in 2010 and has registered
      volunteer donors from different nationalities that live in the Republic of
      Macedonia. The aim of this study was to determine the HLA allele and haplotype
      frequencies of the volunteer donors from the Macedonian Bone Marrow Donor
      Registry and to compare this results with the Macedonians from a family study. We
      analyzed 1,541 donors, with different nationalities, Macedonian, Albanian and
      Macedonian Muslims that were most numerous in MBMDR, and typed them for HLA-A, 
      B, -C, -DRB1, whereas Macedonian also for HLA-DQA1 and HLA-DQB1 by SSO method
      (One Lambda, CA, USA). The most frequent alleles in Macedonians were HLA-A*02,
      01, 24; HLA-B*35, 18, 51; HLA-C*07, 04, 12; HLA-DRB1*11, 16, 13; HLA-DQA1*01, 05
      and HLA-DQB1*05, 03, 06; in Albanians they were HLA-A*02, 24,01; HLA-B*51, 18,
      35; HLA-C*07, 04, 12, HLA-DRB1*11, 13,16; and in Macedonian Muslims they were HLA
      A*02, 01, 24; HLA-B*18, 51, 35, HLA-C*07, 04, 02 and HLA-DRB1*11, 16, 14. The
      most common haplotype in Macedonian was HLA-A*01-B*08-C*07-DRB1*03, whilst in
      Albanian and Macedonian Muslims HLA-A*02-B*18-C*07-DRB1*11. The comparison of the
      HLA allele groups between Macedonian from MBMDR and family study showed similar
      distribution. This study confirmed the close relationship between the populations
      that live in the Balkan Peninsula.

PMID- 30188012
TI  - An Energy-Efficient One-Pot Swelling/Esterification Method to Prepare Cellulose
      Nanofibers with Uniform Diameter.
AB  - An energy-efficient method has been developed to prepare 3-5 nm-wide carboxyl
      functionalized cellulose nanofibers (CNFs) from pulp fiber by a simple one-pot
      swelling followed by esterification process. Tetrabutylammonium acetate
      (TBAA)/dimethyl sulfoxide (DMSO) binary solvent is used as the swelling agent and
      the esterification medium admixed with maleic anhydride. All steps are performed
      at room temperature and no post-mechanical treatment is needed. The highly
      efficient defibrillation of pulp fiber to CNFs is thought to be due to two
      factors: 1) swelling in TBAA/DMSO effectively loosens the structure of cellulose
      supermolecules by breaking the intra- and intermolecular hydrogen bonds between
      cellulose chains; and 2) the carboxyl groups grafted onto the cellulose molecules
      by esterification prohibit the reformulation of hydrogen bonds between cellulose
      chains and therefore stabilize the disperse CNFs with uniform diameter in
      solution. Other than acid anhydride, no catalyst is added for the esterification,
      which facilitates the recycling and reuse of the binary solvent. This energy
      efficient one-pot method could facilitate the large-scale manufacture of bio
      based nanomaterials.

PMID- 30188013
TI  - A Mindfulness-Based Intervention: Differential Effects on Affective and
      Processual Evolution.
AB  - OBJECTIVES: A 20-minutes-a-day, self-help, mindfulness-based intervention was
      conducted for 6 weeks with a French community sample. First, the intervention
      effects on affective and functioning variables were evaluated. Then, a
      differential approach was used to examine improvement potentiality and the
      perceived benefits of mindfulness according to the participants' baseline
      mindfulness competencies. METHOD: Participants were non-randomly assigned to a
      control group on the waiting list (n = 44) or a mindfulness group (n = 47). Self
      report measures assessed anxiety, depression, psychological distress,
      mindfulness, negative self-oriented cognition, and experiential avoidance.
      RESULTS: Improvements in the variables were observed for the mindfulness group
      but not for the control group, with effect sizes ranging between .53 and .88. Low
      baseline levels of mindfulness predicted greater improvement in mindfulness (r = 
      0.55, p < .001) than high baseline levels. CONCLUSIONS: Mindfulness practice
      elicited several positive outcomes regarding affective variables, highlighting
      emotional functioning changes.

PMID- 30188014
TI  - Retinal vein occlusion and obstructive sleep apnea: a series of 114 patients.
AB  - PURPOSE: Evaluate the prevalence of obstructive sleep apnea (OSA) in patients
      with retinal vein occlusion (RVO). METHODS: A prospective and controlled study
      including 114 patients from January to September 2016, who were divided into two
      groups: 69 patients with RVO (RVO+) and 45 controls (RVO-), matched for age, sex
      and disease. All the patients completed a simple questionnaire and the Epworth
      Sleepiness Scale and underwent a RUSleeping(r) (portable monitoring device and
      then continuously monitored the subject's respiration to detect respiratory
      events). In addition, all patients with RVO were administered OSA screening with
      a polysomnography (PSG) during an overnight stay in the hospital, which was
      analysed by a single sleep apnea specialist. RESULTS: Sleep apnea was suspected
      in 73.9% in the RVO group and 63% in the control group based on the simple
      questionnaire; 22% in the RVO group and 4.3% in the control group according to
      the Epworth Sleepiness Scale; 82.6% in the RVO group and 55.6% in the control
      group (p = 0.005) according to RUSleeping(r) . Multivariate logistic regression
      analysis (based on RUsleeping(r) ) confirmed that RVO was associated with OSA
      (adjusted odds ratio, 5.65, [1.60-19.92], p = 0.007). All patients in the RVO
      group were confirmed by PSG, and finally, 91.5% were diagnosed with moderate-to
      severe OSA. Among the RVO+ patients, the mean apnea-hypopnoea index (AHI) was
      42.2 events per hour (7.7-96.5). OSA was moderate in 22% patients and severe in
      69.5% patients. There was no significant relationship between RVO severity and
      the PSG data variables. CONCLUSION: The systematic screening of OSA with the gold
      standard PSG found a high prevalence of OSA in patients with RVO. The OSA is
      probably a risk factor associated with RVO. Polysomnography remains the gold
      standard method; nevertheless, the RUsleeping(r) RTS portable monitoring device
      can assess the presence and severity of sleep apnea with a low failure rate and a
      single use, prior to PSG, which is less available in clinical practice. Further
      studies with larger samples are needed to clarify the association.

PMID- 30188017
TI  - Interactions of phenethylamine-derived psychoactive substances of the 2C-series
      with human monoamine oxidases.
AB  - Psychoactive substances of the 2C-series (2Cs) are phenethylamine-derived
      designer drugs that can induce psychostimulant and hallucinogenic effects.
      Chemically, the classic 2Cs contain two methoxy groups in positions 2 and 5 of
      the phenyl ring, whereas substances of the so-called FLY series contain
      rigidified methoxy groups integrated in a 2,3,6,7-tetrahydrobenzo[1,2-b:4,5
      b']difuran core. One of the pharmacological features that has not been
      investigated in detail is the inhibition of monoamine oxidase (MAO). Inhibition
      of this enzyme can cause elevated monoamine levels that have been associated with
      adverse events such as agitation, nausea, vomiting, tachycardia, hypertension, or
      seizures. The aim of this study was to extend the knowledge surrounding the
      potential of MAO inhibition for 17 test drugs, which consisted of 12 2Cs (2C-B,
      2C-D, 2C-E, 2C-H, 2C-I, 2C-N, 2C-P, 2C-T-2, 2C-T-7, 2C-T-21, bk-2C-B, and bk-2C
      I) and five FLY analogs (2C-B-FLY, 2C-E-FLY, 2C-EF-FLY, 2C-I-FLY, and 2C-T-7
      FLY). The extent of MAO inhibition was assessed using an established in vitro
      procedure based on heterologously expressed enzymes and analysis by hydrophilic
      interaction liquid chromatography-high resolution tandem mass spectrometry.
      Thirteen test drugs showed inhibition potential for MAO-A and 11 showed
      inhibition of MAO-B. In cases where MAO-A IC50 values were determined, values
      ranged from 10 to 125 MUM (7 drugs) and from 1.7 to 180 MUM for MAO-B (9 drugs).
      In the absence of detailed clinical information on most test drugs, it is
      concluded that a pharmacological contribution of MAO inhibition cannot be
      excluded and that further studies are warranted.

PMID- 30188018
TI  - A rapid non-target screening method for determining prohibited substances in
      human urine using liquid chromatography/high-resolution tandem mass spectrometry.
AB  - Target analysis using liquid chromatography-tandem mass spectrometry is applied
      for rapidly detecting various prohibited doping substances. Frequent modification
      is required as additional substances are prohibited. We developed and validated a
      non-target screening method requiring no further modification because it analyzes
      the full spectrum of data in fixed m/z ranges. Urine samples were extracted using
      solid-phase extraction and analyzed by employing a method that combines full scan
      and variable data independent acquisition using high-resolution mass
      spectrometry; and all prohibited substances in the urine samples were
      successfully detected using our screening method. The method was validated in
      terms of specificity (no interferences), recoveries (29%-131%), matrix effects
      (35%-237%), limites of detection (0.0002-100 ng/mL), and intra- and inter-day
      precisions (coefficients of variation lower than 25%). The applicability of this
      method to doping tests was evaluated by analyzing 14 urine samples. As a result,
      the non-target screening method is efficient for conducting anti-doping tests
      because it can be applied without any further modification to prohibited drugs as
      well as to unknown targets that can be prohibited in the future.

PMID- 30188015
TI  - Trends in treatment and survival of patients with nonresected, nonmetastatic
      pancreatic cancer: A population-based study.
AB  - BACKGROUND: Nonresected, nonmetastatic (NR-M0) pancreatic cancer involves both
      locally advanced pancreatic cancer and patients who did not undergo resection due
      to poor health status or patient preference. This study investigates nationwide
      trends of characteristics, treatment, and survival of patients with NR-M0
      pancreatic cancer. METHODS: From the Netherlands Cancer Registry, all patients
      diagnosed with pancreatic cancer between 2006 and 2014 were selected.
      Chemotherapy and overall survival (OS) of NR-M0 patients were evaluated for 3
      year time periods and 2 age groups using chi-square tests for trend and Cox
      proportional hazard regression analysis. RESULTS: Of 18 234 patients, 33% had NR
      M0 pancreatic cancer, which decreased over time (in consecutive 3-year periods:
      38%-33%-28%, P < 0.001). Of 5964 NR-M0 patients, 52% was over 75 years of age,
      16% received chemotherapy, and median OS was 5.1 months. Chemotherapy use
      increased over time in younger patients (<75 years: from 23 to 36%, P-trend <
      0.001, >=75 years: 3% to 4%, P-trend = 0.053). In multivariable survival
      analysis, elderly age, low SES, nonconfirmed cancer, stage II-III disease, and
      earlier years of diagnosis were independently associated with a worse OS. Age of
      patients who received chemotherapy increased over time (median 62-66 years) and
      median OS was 10.4 months without significant differences between time periods (P
      = 0.177) or age groups (P = 0.207). CONCLUSIONS: Overall survival of NR-M0
      pancreatic cancer remains poor which is partly related to advanced age of many
      patients. Despite an increase, chemotherapy is infrequently used. Future research
      should investigate to what extent the more widespread use of chemotherapy could
      improve survival in relation to age-related morbidity.

PMID- 30188019
TI  - Chunk-Based Memory Constraints on the Cultural Evolution of Language.
AB  - In the fields of linguistics and cognitive science, considerable attention has
      been devoted to the question of how linguistic structure emerged over
      evolutionary time. Here, we highlight the contribution of a fundamental
      constraint on processing, the Now-or-Never bottleneck. Language takes place in
      the here and now, with the transience of acoustic speech signals and our
      exceedingly limited memory for sound sequences requiring immediate processing. To
      overcome this bottleneck, the cognitive system employs basic chunking mechanisms
      to rapidly compress and recode incoming linguistic input into increasingly
      abstract levels of representation, thereby prolonging its retention in memory.
      Our suggestion is that these chunk-based memory processes influence linguistic
      structure across multiple time scales. Chunk-based memory constraints govern
      language acquisition and processing on the level of the individual. Through
      usage, linguistic structures that are more easily chunked will tend to
      proliferate, thus shaping the cultural evolution of language across generations
      of language users. This results in a selection of learnable structures, from
      individual words to multiword sequences that are optimally "chunkable," so as to
      better squeeze through the Now-or-Never bottleneck. From this perspective,
      language can be thought of as an adaptive system that culturally evolves to fit
      learners' cognitive capabilities, thereby resulting in the structure it bears
      today.

PMID- 30188020
TI  - Genetic characterization of parvoviruses in domestic cats in Henan province,
      China.
AB  - Feline panleukopenia virus (FPV) and canine parvovirus (CPV) infections are
      highly contagious and cause serious enteric diseases, with high fatality rates of
      cats and dogs. Given the importance of cats as a potential source of genetic
      diversity for parvoviruses, parvovirus strains detected in cats with
      gastroenteritis signs were analysed, and molecular characterisation, sequence
      analysis and phylogeny were evaluated on the VP2 gene. The results showed that
      FPV, new CPV-2a, and CPV-2 are co-circulating in the cat population in Henan
      province of China. Moreover, CPV-2 strains (F2016020, and F2016021) with
      Ser297Ala substitution in VP2 protein was for the first time detected in cats
      with clinical gastroenteritis. This study provided new important findings about
      the evolutionary of parvovirus infection in domestic cats.

PMID- 30188021
TI  - A follow-on study on vision-related quality of life assessment using the NEI-VFQ
      25 in those with a history of unilateral and bilateral congenital cataracts.
AB  - PURPOSE: To assess vision-specific health-related quality of life (using the NEI
      VFQ-25), educational attainment and visual acuity (VA) in patients with a history
      of congenital cataracts and appraise these in relation to Kirwan et al.'s
      (Pediatr Ophthalmol Strabismus 49, 2012, 26) study. METHODS: A retrospective
      hospital-based study of patients with unilateral and bilateral congenital
      cataracts whounderwent surgery aged younger than 12 months. Those 13 years or
      older at follow-up were selected for inclusion. Patients with glaucoma, other
      associated ocular complications or systemic abnormalities were excluded.
      Educational attainment and VA at latest review were recorded. RESULTS: Twelve
      patients with unilateral cataract (mean age: 26 +/- 4.5) and fifteen with
      bilateral cataract (mean age 22 +/- 4.3) were included. Bilateral group had
      greater difficulty with near and distance activities, vision-specific role
      difficulties, vision-specific dependency and general health than the unilateral
      group. There were no significant differences with regard to ocular pain, vision
      specific social functioning, vision-specific mental health, driving, colour
      vision, peripheral vision or educational attainment between the groups. All
      patients attended mainstream school, and majority progressed to third-level
      education. Follow up at an increased time from surgery - 6.2 +/- 5.13
      (unilateral) and 6.5 +/- 6.4 years (bilateral) - compared to Kirwan et al.'s
      study. CONCLUSION: Results were in keeping with Kirwan et al.'s. Bilateral group
      had greater difficulty with day-to-day tasks compared to the unilateral group,
      including near and distance vision activities. They had greater vision-specific
      role difficulties and vision-specific dependency. There was no difference between
      the groups in regard to vision-specific social functioning, vision-specific
      mental health or educational attainment. This can be a source of reassurance to
      parents and patients.

PMID- 30188023
TI  - The role of autophagy in age-related macular degeneration (AMD) - studies into
      the pathogenesis of AMD.

PMID- 30188025
TI  - Asia-Pacific Technology and Trend Survey 2016-2017.
AB  - PURPOSE: To report the results of a survey conducted among retina specialists in
      the Asia-Pacific region on real-life practice patterns in the management of
      vitreoretinal diseases. DESIGN: Prospective study. METHODS: In 2016 and 2017, a
      link was sent to 1400 retinal specialists across the Asia-Pacific region by e
      mail, which directed to a web-based questionnaire (Google forms or Survey Monkey)
      with secure confidential access. The study had institutional review board
      approval. Answers to some of the common questions were compared with the 2016
      American Society of Retina Specialists domestic and global trends. RESULTS: The
      surveys of 2016 and 2017 received 539 (38.5%) and 200 (14.3%) responses,
      respectively, across the Asia-Pacific region. Of the respondents, 85% practiced
      combined medical and surgical retina. The survey indicated that ranibizumab was
      the drug of choice (41% of respondents) in the management of wet age-related
      macular degeneration. In the management of polypoidal choroidal vasculopathy,
      both combination of verteporfin photodynamic therapy (vPDT ) and anti-vascular
      endothelial growth factor (VEGF) (n = 59%) and intravitreal aflibercept
      monotherapy (n = 53%) were preferred. Anti-VEGF treatment remained the first
      choice for center-involving diabetic macular edema (DME) (n = 78%) and switch to
      dexamethasone implant in nonresponding DME was preferred after 2-3 anti-VEGF
      injections (n = 53%). CONCLUSIONS: The survey revealed information that may be
      close to real-world practices and could be of help to understand the
      transformation of global trends and practices due to evolving evidence and
      technologies.

PMID- 30188026
TI  - [Image of the month. Early sign of pneumonia detected by ultrasound].

PMID- 30188024
TI  - Risk factors for development and progression of diabetic retinopathy in Dutch
      patients with type 1 diabetes mellitus.
AB  - PURPOSE: To investigate risk factors for the development and progression of
      diabetic retinopathy (DR) and long-term visual outcomes in Dutch patients with
      type 1 diabetes mellitus (T1DM). METHODS: Cumulative incidences were calculated
      for DR, vision-threatening DR (VTDR), defined as (pre)proliferative DR and
      diabetic macular oedema, and best-corrected visual acuity (BCVA) <0.5 and <0.3 at
      the most recent eye examination. The following factors were assessed: duration of
      diabetes, age of onset of T1DM, gender, mean HbA1c, HbA1c variability (defined as
      coefficient of variation of five separate HbA1c measurements), mean arterial
      blood pressure, body mass index, albuminuria and lipid profile. We used
      multivariable Cox regression models to identify factors associated with DR
      development and progression to VTDR. RESULTS: We found 25-year cumulative
      incidences of 63% for DR, 21% for VTDR, 2% for BCVA <0.5, and 1% for BCVA <0.3.
      Mean HbA1c (HR 1.023, p < 0.001), HbA1c variability (HR 1.054, p < 0.001), age of
      onset of T1DM (HR 1.024, p < 0.001), HDL cholesterol (HR 0.502, p = 0.002) and
      total cholesterol (HR 1.210, p = 0.029) showed an independent association with
      faster development of any form of DR. The mean HbA1c (HR 1.023, p < 0.001) and
      the presence of albuminuria (HR 2.940, p = 0.028) were associated with faster
      progression to VTDR. CONCLUSION: These data show relatively low cumulative
      incidences of DR, VTDR and visual impairment. Higher mean HbA1c, HbA1c
      variability, age of onset of T1DM and total cholesterol were independently
      associated with the risk of DR development, and a protective association was
      found for HDL cholesterol in subjects with T1DM. Mean HbA1c and presence of
      albuminuria were associated with progression of DR.

PMID- 30188028
TI  - [Acute idiopathic eosinophilic pneumonia in a teenager].
AB  - Acute idiopathic eosinophilic pneumonia is a very rare cause of interstitial lung
      disease in children. Pathophysiological mechanisms and etiology remain poorly
      understood. It manifests as a febrile dyspnea, progressively worsening. Chest X
      ray, performed as first-line, shows bilateral infiltrates. The chest CT confirms
      a diffuse infiltrative pneumopathy and the bronchoalveolar lavage demonstrates
      the presence of alveolar hypereosinophilia. The exclusion of other causes of
      alveolar eosinophilia confirms the diagnosis. A ventilatory support is very often
      necessary. Systemic corticosteroids provides a spectacular clinical improvement,
      without recurrence.

PMID- 30188027
TI  - [How I treat... a pelvic organ prolapse at the doctor's office].
AB  - The use of gynecological pessary to put back up prolapsed organs to their normal
      position appears to be as effective as surgical management to relieve symptoms
      related to uro-genital prolapse and restore body image. This millenary device can
      be used temporarily, awaiting a surgical solution or as a therapeutic test
      (mimicking the effect of a surgical procedure to predict its functional outcome
      or identifying a masked urinary incontinence). It can also represent an
      alternative to surgery (patient choice, women who wish to complete childbearing
      or who are unsuitable for surgery because of medical comorbidities) and thus can
      be used in first intention. Pessary can also be used to confirm or deny the
      responsibility of pelvic organ prolapse for atypical symptomatology as pelvic
      heaviness or pain. However, this use requires adjuvant treatment. In this paper,
      we highlight an original effective process not yet published to optimize the
      tolerance of pessary.

PMID- 30188029
TI  - [Complications of hyperthermic intraperitoneal chemotherapy: about a case of
      acute respiratory distress syndrome].
AB  - For about twenty years, extensive cytoreduction surgery associated to
      hyperthermic intraperitoneal chemotherapy (HIPEC) has been used to treat rare
      peritoneal tumors (mesothelioma, pseudomyxoma) and some digestive and
      gynecological neoplasias infiltrating the peritoneum. This heavy technique is
      associated to significant morbi-mortality but allows to increase lifetime and to
      improve quality of life of patients with these tumours. Complications of this
      technique are principally surgical, but hyperthermic intraperitoneal chemotherapy
      can result in toxic effects, especially for kidney and bone marrow. Lung injury
      due to toxicity of chemotherapeutic agents, sometimes serious and potentially
      leading to acute distress respiratory syndrome (ARDS) has already been described
      in the postoperative period of HIPEC, but never intraoperatively. We report the
      case of an ARDS developing intraoperatively during an extensive cytoreduction
      surgery associated to HIPEC, due to the toxicity of the chemotherapeutic agents.

PMID- 30188030
TI  - ["KCE Trials" : innovation based on practice oriented clinical trials].
AB  - Many questions in healthcare can only be answered after the conduct of clinical
      trials. For medicinal products and medical devices the industry finances most
      studies to bring their products to market. However, there is a need for further
      research in certain areas e.g. children, older people and comparative research of
      different treatment options (comparative effectiveness). In addition,
      interventions that are less industry-driven such as surgery, radiotherapy,
      psychotherapy, diet, physical medicine, needappropriately funded large scale
      clinical trials. Such clinical trials can be a good investment for the government
      and the healthcare payer. At the end of 2015 the Belgian Healthcare Knowledge
      Centre (KCE) received the mission and budget to run a programme of practice
      oriented comparative clinical trials. Two years later the recruitment of patients
      in the first trials is ongoing. In addition to its yearly national calls for
      trial proposals, early in 2018 KCE launched its first international common call
      for comparative clinical trials with its Dutch counterpart ZonMw (BeNeFIT).

PMID- 30188031
TI  - [The urgent need for a new ecosystem in healthcare].
AB  - The key performance indicators in healthcare illustrate that the system we run
      nowadays is no longer sustainable. There is an urgent need for fundamental
      changes within the current ecosystem, if we want to maintain or improve the
      levels of quality, security and equity in healthcare. Disruptive technologies
      profoundly modify all domains of our society. Those changes, driven by technical
      convergence, are particularly rapid and extensive in the fields such as big data
      and analysis, artificial intelligence, cloud and blockchain. These continuously
      evolving technologies could potentially offer opportunities to efficient problem
      solving in the health care sector. The culture of our organizations needs major
      changes and especially adaptability and fast speed integration to a process which
      is inevitable.

PMID- 30188032
TI  - [Inflammatory bowel disease and venous thromboembolisms].
AB  - Inflammatory Bowel Diseases (IBD) are associated with lots of extra-intestinal
      complications. Among them, venous and arterial thromboembolisms lead to high
      rates of morbidity and mortality. They often occur during an IBD flare and seem
      to be mostly provoked by acquired factors. The prevention mainly resorts to
      heparin, which is not used enough in spite of its effectiveness. Its indications
      have recently been upgraded to outpatients. In this review, we describe the
      epidemiological and aetiological features of these manifestations, as well as
      their prevention and management. Only venous thromboembolisms are considered.

PMID- 30188033
TI  - [What's new in the treatment of suppurative hidradenitis in 2018 ?]
AB  - Hidradenitis suppurativa (HS), also known as Verneuil's disease and acne inversa,
      is a chronic inflammatory skin disease characterized by a dysfunction of the
      pilosebaceous structures resulting in occlusion and inflammation. The disease
      usually starts after puberty, on average between twenty and thirty years, with
      subcutaneous painful inflammatory nodules, abscess collections, fistulization and
      scars mainly in the axillary, inguinal, sub-mammary, perineal and perianal
      regions. It is a multifactorial disease with the most commonly cited risk factors
      or aggravating factors being smoking, obesity, and HS family history. The first
      line of treatment relies on antibiotics, including tetracyclins, clindamycin and
      rifampycin. In case of non-response, TNF? antagonists, more specifically
      adalimumab, may be considered.

PMID- 30188034
TI  - [Meckel's diverticulum : state of the art].
AB  - The persistence of the embryonic vitelline duct can lead to omphalomesenteric
      duct anomalies. A wide variety of anomalies, depending on the remnant segment and
      its degree of involution, may occur as a result of the omphalomesenteric duct
      failing to obliterate completely. The most frequent omphalomesenteric duct
      anomaly is Meckel's diverticulum, which is present in approximately 2-3 % of the
      population. Despite the progress in medical imaging, conventional abdominal
      computed tomography and endoscopy have limitations for the diagnosis of Meckel's
      diverticulum. The laparoscopic exploratory remains the best choice for diagnosis
      and treatment.

PMID- 30188036
TI  - [Emission Inventory and Prediction of Non-road Machineries in the Yangtze River
      Delta Region, China].
AB  - An air pollutant emission inventory of non-road machineries for the Yangtze River
      Delta (YRD) region was developed, based on local surveys and relative indicator
      predictions for cities in the region. Population, fuel consumption, and air
      pollutant emissions of non-road machineries were predicted for the period 2005 to
      2025. The population of non-road machineries in the YRD region in 2014 was
      8.23*106 units, diesel consumption was about 9.95*106 t, and SO2, NOx, CO, VOCs,
      PM10, and PM2.5 emissions were 5.5*103, 4.9*105, 7.6*105, 1.1*105, 2.9*104, and
      2.7*104 t, respectively. Agricultural machineries accounted for 93% of the total
      population, with their CO and VOC emissions contributing 88% and 77% of
      respective totals. Construction machineries contributed 49% and 35% of NOx and
      PM2.5 emissions. Air pollutant emissions from non-road machineries were mainly
      concentrated in the middle and northern cities of the YRD region. During the
      period 2005-2014, the growth rates of population, fuel consumption, and air
      pollutant emissions of non-road machineries in the YRD region were relatively
      high. It is estimated that growth will be slowing down in 2020 and 2025. Diesel
      consumption will increase by 2% and 8% in 2020 and 2025, respectively, compared
      with 2014 levels. By 2020, SO2, NOx, CO, VOCs, PM10, and PM2.5 emissions will
      decrease by 97%, 10%, 3%, 10%, 11%, and 11%, respectively; by 2025, these
      decreases will reach 97%, 16%, 3%, 15%, 21%, and 21%, respectively. It is
      expected that air pollutant emissions from non-road machineries will continue to
      decline in future. However, the decreasing trend of NOx, VOCs, and PM2.5
      emissions from motor vehicles reached 22%, 50%, and 48%, much greater than that
      of non-road machinery. The emission contributions of non-road machinery will
      become increasingly significant in future. It is necessary to accelerate the
      scrappage of old machinery and to further promote emission standards for new
      machinery to reduce emissions from non-road machineries.

PMID- 30188035
TI  - [Trimbow(r) : twice-daily triple combination for the treatment of COPD].
AB  - Single-inhaler triple therapy in extrafine solution combining an inhaled
      corticosteroid (ICS), the dipropionate of beclometasone, a long acting beta2
      agonist (LABA), the fumarate of formoterol and an long-acting muscarinic
      antagonist (LAMA), the bromide of glycopyrronium, was developed for the treatment
      of the chronic obstructive pulmonary disease (COPD). Trimbow(r) is the first
      triple therapy in spray with fixed dose and containing 3 pharmacological agents
      (LABA-LAMA-ICS). Clinical trials show that Trimbow(r) improves numerous
      parameters such as the respiratory function, the quality of life, the symptoms
      and the rate of moderate to severe exacerbations while being tolerated well.
      These results justify its use in severe and very severe COPD with exacerbations
      in spite of treatment by LABA-LAMA or LABA-ICS. In this article, we present a
      brief synthesis of the main recent clinical trials on Trimbow(r), its comparison
      with other pharmacological agents/associations regularly used in the treatment of
      COPD, as well as some practical information on its use in routine.

PMID- 30188038
TI  - [Historical Trends of Atmospheric Pb and Hg Emissions from Fossil Fuel Combustion
      in Shanghai].
AB  - Rapid urbanization in Shanghai over the past century has led to increased
      resource and energy consumption, in turn leading to the release of significant
      amounts of toxic pollutants into the urban environment. In order to investigate
      historical variations in atmospheric metal emissions from typical combustion
      sources in Shanghai, historical emissions of Pb and Hg from coal-fired sectors
      (coal-fired power plant, industrial sector, and domestic use) and vehicle exhaust
      in Shanghai during the period 1949-2015 were estimated, based on consumption of
      fossil fuels (coal and gasoline) and emission factors. Results showed that Pb and
      Hg emissions exhibited rapidly fluctuating increases from 1949 to the 1980s or
      1990s, before beginning to decrease sharply due to various pollution control
      measures. Hg emissions from coal-fired sources played a dominant role during the
      1980-2015 period, contributing a high proportion (87.5%-99.7%) to the total. The
      dominant sources of atmospheric Pb emissions have experienced historical
      variations. Coal-fired emissions became the major contributor (78.2%-83.5% of
      total) following omission of leaded gasoline from the Shanghai market since 1997.
      However, the rapid increase of gasoline consumption since 2005 has led to
      gasoline-fired emissions again becoming the main contributor (55.5%-79.1%).

PMID- 30188037
TI  - [Vehicle Exhaust Emission Characteristics and Their Contributions in Jiangsu
      Province].
AB  - An hourly vehicular emission inventory with 1 km*1 km resolution was developed
      for Jiangsu Province in 2015, using the COPERT model and ArcGIS technology. The
      improved "standard road length" method, as well as road network information and
      monthly, weekly, and daily variations of the congestion delay index were used to
      increase temporal-spatial resolution. The contributions of different vehicle
      types, emission standards, and road types to total vehicular emissions were
      analyzed. Results showed that vehicular emissions of NOx, HC, CO, PM2.5, SO2, OM,
      and BC were 490.9, 166.3, 1614.8, 16.9, 1.9, 3.6, and 6.7 thousand tons,
      respectively. On average, Suzhou and Xuzhou contributed 34%-45% of the total.
      Evaporative emissions of HC were 20.2 thousand tons, accounting for 12% of total
      HC emissions. Small passenger cars and motorcycles were the major HC and CO
      contributors, accounting for over 30% of total emissions. Heavy-duty diesel
      trucks contributed 36%-54% to NOx, PM2.5, SO2, OM, and BC emissions, representing
      much higher emissions than other vehicles. Heavy-duty and medium-duty diesel
      trucks in Suzhou and Xuzhou are the main sources of NOx and PM2.5emissions. China
      III diesel vehicles account for the largest share (42%-55%) of NOx, PM2.5, SO2,
      and BC emissions. China III heavy-duty diesel trucks and China 0 medium-duty
      diesel trucks are the primary and secondary contributors of NOx, PM2.5, OM, and
      BC emissions, with a total share of 40%-56%. China 0 motorcycles contributed
      about 16% to total HC and CO.

PMID- 30188039
TI  - [Emission Inventory of Atmospheric Pollutants and VOC Species from Crop Residue
      Burning in Guangdong Province].
AB  - An emission inventory of atmospheric pollutants from crop residue burning in
      Guangdong for the period 2008-2016 was developed, based on crop yield data.
      Emissions of species of volatile organic compounds(VOCs)and corresponding ozone
      formation potential (OFP) in 2016 were also estimated. Results showed that
      emissions of atmospheric pollutants from crop residue burning in 2013-2016 were
      lower than in 2008-2012. This was mainly due to the policy of prohibiting open
      burning of straw and to improvement of rural living standards, which reduced the
      proportion of straw burning. In 2016, emissions of SO2, NOx, NH3, CH4, EC, OC,
      NMVOC, CO, and PM2.5 were 2443.7, 16187.9, 6943.8, 29174.4, 3625.5, 14830.7,
      65612.6, 591613.9, and 49463.0 t, respectively. Rice straw burning was the main
      source of pollutants, accounting for about 68.55% of total pollutant emissions.
      The five municipalities with highest atmospheric pollutant emissions were
      Zhanjiang, Maoming, Meizhou, Zhaoqing, and Shaoguan, together accounting for
      about 58.63% of total emissions. The top 10 VOC species for mass-based emissions
      consisted of ethylene, acetaldehyde, formaldehyde, benzene, ethyne, propylene,
      ethane, toluene, propane, and propionaldehyde, together contributing 67.91% to
      total emissions. The top ten OFP-based VOC species were ethylene, formaldehyde,
      acetaldehyde, propylene, 1-butylene, propionaldehyde, toluene, acrolein,
      isoprene, and crotonaldehyde, accounting for 80.83% of total OFP.

PMID- 30188040
TI  - [Mass Concentrations and Size Distributions of Water-soluble Inorganic Ions in
      Atmospheric Aerosols in Beibei District, Chongqing].
AB  - In order to study the concentration and distribution characteristics of water
      soluble inorganic ions in aerosol particles of the Beibei district of Chongqing,
      aerosol samples were collected with an Andersen cascade impactor between March
      2014 and February 2015. Water-soluble inorganic ions, including Na+, NH4+, K+,
      Mg2+, Ca2+, F-, Cl-, NO3-, and SO42- were determined for different particle sizes
      (9.00, 5.80, 4.70, 3.30, 2.10, 1.10, 0.65, and 0.43 MUm) using the ion
      chromatography method. Results showed that SO42-, NH4+, NO3-, Cl-, Na+, and K+
      were mainly distributed in fine particles, while Mg2+, Ca2+, and F- were mainly
      present in coarse particles. SNA (SO42-, NH4+, and NO3-) exhibited clear unimodal
      distribution, with peaks in the droplet mode of 0.65-1.10 MUm, mainly present in
      the form of (NH4)2SO4 and NH4NO3 in fine particles. The formation of SO42- is
      mainly attributed to in-cloud processes and partly to oxidation of SO2. Na+, Cl-,
      and Mg2+ exhibited bimodal distribution in coarse and fine particles; K+ was a
      single peak distribution in the range of 0.43-1.10 MUm, while peaks of F- and
      Ca2+ concentrations were in coarse particles. Average annual concentrations of
      total water-soluble ions in PM2.1 and PM9.0 were (32.68+/-15.28) MUg.m-3and
      (48.01+/-19.66) MUg.m-3 over the observation period. Seasonal variations of PM2.1
      and PM9.0concentrations decreased in the order of winter > spring > summer >
      autumn. This was the same for most ions, but a small number of ions (F-, Mg2+ and
      Ca2+) had a different pattern in the spring, summer, and winter. The SNA were the
      major components of water-soluble ions in PM2.1, and Ca2+ was the major component
      of water-soluble ions in PM9.0 besides SNA. The concentration of cations was
      significantly higher than that of anions' in PM2.1 and PM9.0, with a certain
      correlation between different ions. Emissions from motor vehicle exhaust,
      combustion processes, soil sources, and fugitive dust were the major sources of
      water-soluble ions in this area. The effect of air temperature on secondary ions
      is significant (P<0.05), but relative humidity and wind speed have no significant
      effect (P>0.05).

PMID- 30188041
TI  - [Analysis of Seasonal Variations in Chemical Characteristics and Sources of PM2.5
      During Summer and Winter in Ji'nan City].
AB  - To investigate seasonal variations in the chemical compositions of aerosols in
      Ji'nan City, PM2.5 samples were collected during summer and winter in 2015. The
      sampling period lasted one month during each season. PM2.5 samples were analyzed
      for the composition, concentration, and sources of water-soluble inorganic ions,
      organic carbon (OC), elemental carbon (EC), and water-soluble organic carbon
      (WSOC). Results showed that mass concentrations of PM2.5 in winter were about
      twice those in summer, and concentration levels varied between fine and
      excellent. The concentrations of total water-soluble inorganic ions were also
      higher in winter than in summer, with SO42-, NO3-, and NH4+ being the dominant
      species and well correlated with each other. NH4+ in PM2.5 mostly existed in the
      form of (NH4)2SO4 and NH4NO3 in both summer and winter. There was strong
      secondary oxidation of SO2 and NO2. The sulfate oxidizing rate (SOR) was higher
      in summer than in winter, while the nitrate oxidizing rate (NOR) showed the
      opposite trend. The ratio of anions to cations in both summer and winter were
      less than one, suggesting that PM2.5 were slightly alkaline. The ISORROPIA-II
      mode showed that acidity in winter was stronger than in summer. Concentations of
      OC and EC were both higher in winter than in summer. The ratios of OC to EC and
      WSOC to OC and estimated concentrations of secondary organic carbon (SOC) showed
      that secondary pollution was more serious in winter than in summer. Principal
      component analysis(PCA)indicated that the major sources contributing to inorganic
      ions were secondary oxidation and biomass burning in summer, and coal combustion
      and secondary pollutants formed by chemical oxidation of precursors emitted from
      coal combustion in winter.

PMID- 30188042
TI  - [PM2.5 Pollution Characterization and Cause Analysis of a Winter Heavy Pollution
      Event, Liaocheng City].
AB  - Heavy pollution events frequently occur during fall and winter seasons in
      northern areas. In order to understand the characteristics and chemical
      composition of PM2.5 during heavy pollution in winter in Liaocheng City, ambient
      PM2.5 samples were collected between January 7-11,2016. Mass concentration, water
      soluble ions, carbonaceous species, and elements were analyzed, as well as the
      causes of pollution. Results showed that PM2.5 mass concentration was 238.3 MUg.m
      3 with the trend clearly that of an inverted V; this concentration represents
      exceedance of the National Ambient Air Quality Standard (GB 3095-2012) by more
      than 2.2 times. NO3-, SO42-, and NH4+(SNA)were the main water-soluble ions. As
      pollution increased or decreased, NH4+, SO42-, NO3-, and Cl- exhibited the same
      trend, which contrasted with that of Ca2+. During the peak of pollution, NH4+,
      NO3-, and SO42- concentrations were 48.96, 68.45, and 80.55 MUg.m-3, with these
      representing levels 6.29, 7.31, and 7.84 times those of the initial stage,
      respectively. During the pollution event, OC and EC concentration variation
      ranges were 20.8-60.2 MUg.m-3, and 3.0-7.5 MUg.m-3, respectively. The
      concentration of OC was significantly higher than that of EC and the variation
      amplitude was significantly larger. During the event, the mass concentrations of
      27 inorganic elements on each day were 10.2, 22.4, 16.0, 19.6, and 8.2 MUg.m-3,
      respectively. Enrichment factors (EF) of all elements were less than 10,
      indicating lack of enrichment and showing that sources were mainly natural. PM2.5
      mass concentration reconstruction results showed that organic matter (OM), SO42-,
      and NO3- were major components, followed by NH4+, crustal material, and other
      ions. EC and trace element content was relatively low. As PM2.5 pollution
      worsened, secondary inorganic salt (NH4+, SO42-, NO3-) concentrations and
      proportions increased, OM concentration increased but its proportion decreased,
      while crustal material concentration and proportion both decreased, showing that
      secondary inorganic conversion was the main cause of this pollution event, mainly
      driven by coal and motor vehicle emissions.

PMID- 30188043
TI  - [Concentrations, Sources, and Dry Deposition Fluxes of Different Forms of
      Phosphorus in Qingdao Aerosols in Summer].
AB  - Total suspended particulate (TSP) samples were collected in Qingdao from June to
      July 2016. Different forms of phosphorus in these samples-including total
      phosphorus (TP), dissolved phosphorus (DP), dissolved inorganic phosphorus (DIP),
      and dissolved organic phosphorus (DOP) were analyzed to investigate their
      distribution characteristics and sources, as well as their dry deposition fluxes.
      Results showed that the mass concentration of TP in aerosols was (49.3+/-30.6)
      ng.m-3, and the concentration of DP was (15.5+/-10.4) ng.m-3, accounting for
      30.9%+/-11.0% of TP. DIP dominated in dissolved state P, contributing about 60%.
      The sources of different forms of P were analyzed, showing that the P in Qingdao
      aerosols in summer was derived from both crustal and anthropogenic sources, with
      the latter including biomass burning and agricultural fertilization. TP was
      mainly derived from soil sources, which contributed 38%, while the contribution
      of agricultural activities and industrial sources was about 20%. DIP in DP was
      mainly derived from agricultural activities and combustion sources, with
      contributions of 51% and 24%, respectively. DOP was mainly derived from soil
      sources and agricultural activities, contributing 41% and 27% respectively. The
      dry deposition flux of TP in Qingdao was (51.7+/-31.7) MUg.(m2.d)-1, of which
      23.2%+/-8.2% was the water-soluble fraction. DOP in the total dry deposition flux
      of DP was non-negligible, accounting for 40%. The atmospheric deposition of
      soluble P would support phytoplankton carbon production of (0.5+/-0.3) mg.(m2.d)
      1, contributing about 1% to new productivity in the Yellow Sea.

PMID- 30188044
TI  - [Characteristics and Source Apportionment of Ambient Volatile Organic Compounds
      in Winter in Jincheng].
AB  - Air samples were collected and analyzed by GC-MS to investigate the component
      characteristics of volatile organic compounds (VOCs) in winter in Jincheng. PMF,
      ratio analysis, and the backward trajectory model were used to investigate
      sources of VOCs. Ozone formation potential and secondary organic aerosol
      formation potential were calculated, in order to analyze the environmental
      implications of detected VOCs. Results showed that the average concentration of
      VOCs was 93.35 MUg.m-3 in Jincheng, with the most abundant component being alkane
      (52.91 MUg.m-3 and 56.68% of total VOCs). Based on PMF analysis, five sources of
      ambient VOCs in Jincheng were identified, namely industrial emission sources
      (33.71%), fuel combustion sources (30.27%), vehicle emissions (26.28%), solvent
      evaporation sources (9.00%), and plant emission sources (0.74%). Ratios of B/T
      and i-pentane/n-pentane were 1.58+/-0.68 and 2.07+/-0.43, indicating that VOCs
      were derived from the mixture of road and coal combustion sources. Clustered
      analysis of the air mass backward trajectory showed that three air masses
      cluster, which were accounting for 50%, 25% and 25% of the total back
      trajectories respectively, all came from the northwest, and industrial pollution
      from the northwest might therefore significantly influence VOCs in Jincheng. With
      low wind speed (<3 m.s-1), the air quality index, concentration of total VOCs,
      and contribution rate of vehicle emissions were 143, 162.48 MUg.m-3, and 46.16%,
      respectively, higher than values at faster wind speeds (3-6.9 m.s-1). Ozone
      formation potential and secondary organic aerosol formation potential of aromatic
      hydrocarbons, which had the highest formation potential, were 98.89 MUg.m-3 and
      1.21 MUg.m-3, respectively, accounting for 37.28% and 97.01% of total formation
      potential. To reduce the pollution of VOCs in Jincheng, it is important to
      control industrial emissions, vehicle emissions, and fuel combustion emissions.

PMID- 30188045
TI  - [Enrichment Levels and Comprehensive Pollution Assessment of Dust Heavy Metals in
      Winter in Beijing].
AB  - Dust reflects the natural subsidence of particles and is thus generally accepted
      as an important environmental indicator. Dust heavy metals find their way into
      soil or water via atmospheric deposition, potentially damaging plants, aquatic
      organisms, as well as human beings. In order to study the concentration levels,
      enrichment degrees, and comprehensive pollution characteristics of the dust heavy
      metals Cd, Cr, Pb, Cu, Zn, Ni, Co, V, Bi, and Mo in winter in Beijing, 49 groups
      of dust samples were collected from different locations within the city from
      November 2013 to March 2014. Heavy metal content (mass percentage) was then
      measured using Elan DRC II type inductively-coupled plasma mass spectrometry (ICP
      MS). Results showed that the average content of Cd, Bi, and Mo was less than 10
      mg.kg-1, that of Co, Ni, and V was between 10 and 100 mg.kg-1, while that of Pb,
      Cr, Cu, and Zn was more than 100 mg.kg-1. The amount of Cd, Zn, and Cu in dust
      samples was generally higher than their secondary standard values in the soil
      environment. The secondary standard excess rates of Cd, Zn, and Cu were 100%,
      97%, and 93.9% in urban environments, and 100%, 100%, and 81.2% in suburban
      environments, respectively. Results also indicated slight enrichment of Bi, Cu,
      Ni, and Pb, mainly derived from crustal or soil sources, while Cd, Cr, Mo, and
      Zn, exhibited mild enrichment, caused by a combination of natural and artificial
      sources. The paper proposes a "dust heavy metal comprehensive pollution index"
      model, based on the traditional single pollution assessment method, so as to
      explore comprehensive pollution characteristics of dust heavy metals in Beijing.
      Results for the dust heavy metal comprehensive pollution index in Beijing City
      were in the order of Cd > Zn > Cu > Pb > Cr > Ni > V > Co. Cd, Zn, Cu, and Pb
      were identified as key pollution factors, with Cd and Zn as primary factors.
      Results for the dust heavy metal comprehensive pollution index in Beijing suburbs
      was Cd > Zn > Cu > Pb > Cr > Ni > Co > V. Cd, Zn, Cu, Pb, and Cr were key
      pollution factors, with Cd and Zn as primary factors.

PMID- 30188047
TI  - [Ozone Generation Potential and Highly Contributing Substances of NMOCs from
      Landfill Working Face].
AB  - Non-methane organic compounds (NMOCs) are major ozone precursors in atmospheric
      photochemical reactions. The working face of a landfill is a significant source
      of fugitive NMOC emissions. In order to control tropospheric ozone pollution, it
      is necessary to minimize NMOCs, and this requires identification of contributing
      substances. In this study, gas samples were collected from the working face of a
      landfill and analyzed. Their ozone formation potential was calculated using the
      propylene-equivalent concentration method and the maximum incremental reactivity
      method. In total, 36 kinds of substances met the standard for detection frequency
      and concentration. The average annual concentration of NMOCs was about 10000
      MUg.m-3, with total concentration greatest in summer. Concentrations of materials
      were as follows:oxygenated compounds > sulfur compounds > halogenated
      hydrocarbons > benzene series > hydrocarbons. Based on the results of the two
      calculation methods, ethanol, m-xylene, propylene, ethyl acetate, and n-pentane
      were found to be significant ozone formation contributors across the whole year.
      The pattern for spring was similar. Contributors to high ozone formation were
      ethanol, 1-butene, toluene, cyclohexane, and styrene in summer and spring, while
      ethanol contributed very significantly in winter. The propylene-equivalent
      concentration method was found to be more suitable for estimating ozone formation
      potential from the working face.

PMID- 30188046
TI  - [Characteristics of Atmospheric BTX near a Main Road in Hefei City].
AB  - In order to study levels of BTX near a main road in Hefei in March 2016, benzene,
      toluene, m-xylene, and o-xylene (BTX) and conventional pollutants (such as NO2
      and SO2) in the atmosphere were monitored through a home-made differential
      optical absorption spectroscopy (DOAS) system. Results showed that average
      concentrations of benzene, toluene, m-xylene, and o-xylene were 21.7, 63.6, 33.9,
      and 98.7 MUg.m-3, respectively. Compared with other cities both in China and
      elsewhere, benzene and toluene pollution can be considered to be of medium level,
      while xylene pollution is serious. Wind direction, T/B ratio, and correlation
      with CO were also analyzed, together with BTX sources. Result showed that the T/B
      ratio was 0.8-4.5, with correlation coefficients of benzene, toluene, and CO of
      0.55 and 0.34, respectively. These values indicate that benzene and toluene are
      mainly derived from automotive emissions, also affected by surrounding industrial
      parks. Xylene is mainly derived from a coating industrial park north of the
      observation site. It was shown that high night-time concentrations of benzene and
      toulene could be due to industrial emissions from the industrial parks around the
      observation site. The ozone formation potential is in the order of o-xylene > m
      xylene > toulene > benzene at the observation site. The ozone formation potential
      of xylene accounted for 85% of total ozone formation potential, indicating that
      emissions from surrounding industrial parks contribute greatly to ozone formation
      in the area.

PMID- 30188048
TI  - [Emission Characteristics of Wind-Eroded Dust from Concrete Batching Plants in
      Beijing].
AB  - Concrete batching plants are a typical source of fugitive dust in Beijing. In
      this study, two concrete batching plants in Beijing were used to test wind
      erosion of dust with a Portable In-suit Wind Erosion Laboratory (PI-SWERL)
      designed by the Desert Research Institute (DRI). Sand and aggregate storage piles
      and paved roads in concrete batching plants were tested to determine the emission
      characteristics of wind eroded dust. Combining the frequencies of disturbance of
      storage piles and paved road surface with local meteorological data, localized
      wind erosion dust emission factors of PM2.5 were established. Results demonstrate
      that:1There are small differences in daily average emission factors for PM2.5
      between the aggregate warehouse entrance area, concrete loading area, social road
      import area, and concrete batching plant entrance area, with these being 0.45,
      0.41, 0.31, and 0.30 kg.(hm2.d)-1, respectively. 2Daily average emission factors
      for PM2.5 of coarse stone, fine stone, coarse sand, and fine sand storage piles
      are 0.10, 0.12, 0.26, and 2.02 kg.(hm2.d)-1, respectively. Emission factors of
      fine sand storage piles are 20.5, 16.8, and 7.7 times greater than those of
      coarse stone, fine stone, and coarse sand, respectively, and spring emission
      factors are 6.4, 3.4, and 1.3 times greater than those of summer, autumn, and
      winter, respectively. 3Daily average emission factors for PM2.5 of storage piles
      and paved roads are 1.13 and 0.37 kg.(hm2.d)-1, respectively 3.9 and 1.3 times
      higher than the wind erosion factor from storage piles from AP-42 files (c11s12
      concrete batching, 1995); the uncertainty range of the emission factor is 34%
      92%. 4It is recommended to strengthen watering, sweeping, and cleaning of paved
      roads, and to ensure fully enclosed storage and use of spray water to reduce wind
      erosion of dust from storage piles, especially from fine sand piles.

PMID- 30188049
TI  - [Seasonal Variation Characteristics of Pollution Risk in a Riverside Source Area
      Based on Source Apportionment].
AB  - Riverbank filtration is internationally accepted as a safe new method for
      extracting drinking water. This paper describes the structure and characteristics
      of pollution sources in the Hulan water source area of Harbin during wet and dry
      seasons, based on groundwater pollution sources apportionment technology.
      Pollution risk of the water source area was also assessed using the pollution
      sources-pathway-receptor model. Impacts on water quality safety under the
      collective effects of seasonal changes and human activities were then analyzed.
      Results showed that groundwater pollution sources have different spatial
      distribution characteristics based on pollution source apportionment during wet
      and dry seasons, with four principal influencing factors:1water-rock interaction
      caused by exploitation of water sources, 2 natural geological processes resulting
      from dissolution of iron manganese minerals, and pollution by 3 nitrogen and 4
      organics in response to human activities. Pollution risk assessment showed that
      water sources were at low risk during both wet and dry seasons. However, the
      south area of the water source area showed high groundwater pollution risk during
      the wet season, while other high-risk areas were mainly distributed around the
      riverbanks and densely populated areas during the dry season. These findings
      indicate that human activities greatly influence groundwater pollution risk
      during the dry season; accordingly, this season should be the focus of integrated
      water quality management and control for the water source area.

PMID- 30188051
TI  - [Composition, Spatial Distribution Characteristics and Source Analysis of
      Chromophoric Dissolved Organic Matter in the Lanzhou Reach of the Yellow River].
AB  - Chromophoric dissolved organic matter (CDOM) in riverine systems can be affected
      by environmental conditions and land-use, and can thus provide important
      information regarding anthropogenic activities in surrounding landscapes. It can
      modify the optical properties of waters and affect the balance and availability
      of dissolved nutrients and metals in water bodies. However, the characteristics
      of CDOM in the Lanzhou reach of the Yellow River have not yet been reported. In
      this study, the optical properties of water samples collected at 32 locations
      during April 2017 across the Lanzhou reach of the Yellow River were examined
      using UV-VIS and excitation-emission matrix fluorescence spectroscopy-parallel
      factor analysis (EEM-PARAFAC), to determine CDOM compositional changes, spatial
      distribution characteristics, and sources. Cluster analysis was used to
      categorize samples into groups of similar pollution levels within a study area.
      Results showed that CDOM was primarily comprised of low molecular weight organic
      substances with aromatic structure belonging to complex "protein-like-humic-like"
      substances, and dominated by protein-like substances (organism sources). Two
      humic-like components (C1, C4), one tryptophan-like component (C2), and one non
      humic-like component (C3) were identified by PARAFAC. Tryptophan-like substances
      were predominant in the components of CDOM, accounting for 51.06% of average
      total fluorescence intensity. Humic-like materials and non-humic-like substances
      accounted for 36.74% and 12.20%, respectively. Weak correlations were observed
      between protein-like substances and humic-like substances, indicating different
      sources of these components. The distribution of total fluorescence intensity
      showed a distinct spatial pattern; trends in fluorescence intensity were weak
      strong-weak along an upstream to downstream continuum, mainly affected by changes
      in the content of protein-like substances. The spatial variation of the CDOM in
      the Lanzhou reach of the Yellow River can therefore be assessed based on protein
      like materials dynamics. Public spaces along rivers offer opportunities for
      community gatherings and recreational activities. However, high-intensity
      anthropogenic activities strongly influence CDOM concentration and composition in
      this area in different ways; sources include increased residential/commercial
      wastewater, catering, water recreation facilities pollution, shipping, and a
      small amount of industrial discharge. In addition, it was concluded that
      endogenetic pollution may become the main source of internal loading in the
      Lanzhou reach of the Yellow River, implying that stronger endogenetic pollution
      control is needed to alleviate CDOM pollution and improve water quality.

PMID- 30188050
TI  - [Evaluation of Effect of Urban Non-point Source Pollution Control on Porous
      Asphalt-Bio-retention Combined Roads].
AB  - Different combinations of low impact development (LID) technologies can be
      applied for control of urban non-point source pollution. There are currently few
      evaluations of urban non-point source pollution and pollution load reduction
      based on a combination of porous asphalt and bio-retention. Taking Shenzhen
      International Low Carbon City as an example, road-deposited sediments were
      collected prior to and after rainfall events. Runoff was monitored under six
      typical rainfall events, from porous asphalt and the inlet/outlet of bio
      retention. Through analysis of changes in the process of "build-up-wash-off
      transport" of pollutant loads, the average build-up of road-deposited sediments
      in the study area was found to be (15.80+/-3.79) g.m-2; the mass percentage of
      road-deposited sediments (size>250 MUm) was approximately 65.14%. The average
      wash-off percentage of six different intensity rainfall events was 17.15%, and
      road-deposited sediments (size<105 MUm) were carried by 62.71%-74.94%. The
      average pollution loads of surface runoff pollutants SS, TN, and TP were 2.02,
      0.025, and 0.0013 g.m-2, respectively. The removal rates of SS, TN, and TP
      through porous asphalt under infiltration and filtration were 70.26%, 46.29%, and
      19.27%, respectively. The secondary purification removal rates of runoff water in
      bio-retention were 85.25%, 20.22%, and 70.27%, respectively. Pollutant loads into
      Dingshan River totaled 0.08, 0.011, and 0.0003 g.m-2, representing 4.05%, 43.47%,
      and 24.39% of runoff. The combination thus had a significant effect on runoff
      purification. Through quantitative research on the formation of non-point source
      pollution, this paper provides a scientific basis for estimating pollution loads
      of urban non-point source pollution and evaluating the performance of LID
      projects. It makes suggestions for the popularization and application of LID and
      sponge city design in China.

PMID- 30188052
TI  - [Characterization of Dissolved Organic Matter Fractions in the Ning-Meng Section
      of the Yellow River and Relationship with Metal Ions].
AB  - Dissolved organic matter(DOM)is an important element of natural aquatic systems.
      Due to differences in their hydrophobic/hydrophilic properties and various
      functional groups, chemical appearances of DOM fractions also vary. In this
      study, seven natural waters, extending from Xiaheyan to Toudaoguai along the Ning
      Meng section of the Yellow river, were sampled in April 2015. Four DOM fractions
      were obtained by pumping through XAD-4 and XAD-8 resins, i.e., hydrophobic acid
      (HOA), hydrophobic base (HOB), weak hydrophobic acid (WHOA), and hydrophilic
      matter (HYI). Based on detection by three-dimensional excitation-emission matrix
      fluorescence (EEM) and correlation analysis, relationships with five metal ions
      (Pb, Zn, Cu, Cr, As) were analyzed. Results show that DOC gradually increased
      along an upstream to downstream continuum in the Ning-Meng section. HYI (small
      molecular proteins) was the main DOM fraction present, followed by HOA,
      suggesting enhanced microbial-sourced impact from industrial sewage discharges.
      The significant peaks of humic-like (A, C) and protein-like compounds (T1) in the
      EEM chart further highlight the effect of endogenous pollution caused by
      wastewater. Furthermore, SPSS fitting results indicate that DOM is correlated
      with all five metal ions, especially with Cu. In terms of the four DOM fractions,
      HYI showed the strongest correlation with Cu, illustrating the significant
      relationship between HYI and Cu during the migration and transformation process.
      Moreover, the fluorescence intensity of protein-like compounds decreased with
      increasing Cu concentration, possibly due to fluorescence quenching caused by
      complexation between Cu and proteins in HYI.

PMID- 30188053
TI  - [Comparative Characteristics of Optical Absorption in Waters from Yiluo River and
      Huntai River in Spring].
AB  - The absorption characteristics, composition, spatial variability, and relative
      contribution of optically active constituents over the range of
      photosynthetically active radiation (PAR, 400-700 nm) were analyzed from samples
      collected in the Yiluo and Huntai Rivers in May 2017 and 2013, respectively.
      Results demonstrated that the absorption curves of total suspended
      particulates[ap(lambda)] were similar to those of non-algae
      particles[ad(lambda)]. Significant correlations between ap(lambda) and ad(lambda)
      were obtained, especially at 440 nm, with r=0.968 in the Yiluo River and r=0.899
      in the Huntai River. Meanwhile, positive correlations between ap(lambda) and the
      absorption of phytoplankton[aph(lambda)] were observed at 675 nm. ap(lambda) in
      the two basins was dominated by ad(lambda). Moreover, the composition of
      auxiliary pigments and chloropyhll a concentration[Chla] showed more significant
      spatial variations based on aph(440)/aph(675) in the Yiluo River than in the
      Huntai River. In addition, CDOM absorption slopes (SCDOM) indicated that CDOM
      composition in the Yiluo River was dominated by exogenous substances; in
      comparison, the Huntai River had more endogenous substances. SCDOM in the Yiluo
      River was lower than in the Huntai River, indicating that the CDOM composition of
      the Yiluo River was inclined towards high molecular weights. Furthermore,
      Mr[aCDOM(250)/aCDOM(365)] showed greater ranges and lower mean values in the
      Yiluo River than in the Huntai River, confirming that CDOM molecular weight
      varied greatly in the former. CDOM molecular weight in the Huntai River was also
      lower than in the Yiluo River, in accordance with SCDOM results.

PMID- 30188055
TI  - [Characteristics and Genesis of NO3 Type Water in Shallow Groundwater in Liujiang
      Basin].
AB  - In recent years, groundwater nitrate pollution has become more and more severe.
      Anthropogenic activities have become more significant, not only causing
      pollution, but also changing the hydrochemical type of groundwater and leading to
      the emergence of NO3 type groundwater. This study focuses on the Liujiang Basin.
      The characteristics and influencing factors of NO3 type water in shallow
      groundwater are analyzed, and the significance of NO3 type water is discussed.
      Results show that shallow groundwater in the Liujiang Basin is of poor quality
      and nitrate pollution is severe. NO3 type water comprises 20.9% of all effective
      data for the area and is mainly distributed in the southeast and a few parts of
      the northern mountainous area. Based on the characteristics of NO3 type water,
      this can be classified as high TDS NO3 type water or low TDS NO3 type water. TDS
      and total hardness concentration values of high TDS nitrate type water are high
      and the concentration range is wide. Conversely, TDS and total hardness
      concentration and the concentration range of low TDS NO3type water are both low.
      The formation of NO3 type water is mainly driven by human domestic sewage,
      agricultural fertilization, and septic tank and landfill leachate infiltration,
      among others. The pollution load of high TDS NO3 type water is generally higher
      than that of low TDS NO3 type water. Analysis of NO3 type water makes it possible
      to prevent and control groundwater pollution when there is an increasing
      pollution trend but pollution is not yet severe.

PMID- 30188054
TI  - [Seasonal Variations in River Water Chemical Weathering and Its Influence Factors
      in the Malian River Basin].
AB  - In order to discern temporal variations, sources, and controlling factors of
      river water chemistry in the Malian River Basin, time series samples were
      collected from the Yuluoping hydrological station in 2016. The compositions of
      major cations and anions were analyzed and a forward model was used to calculate
      the weathering rates of evaporite, silicate, and carbonate. Results showed that
      river water was brackish with average total dissolved solids of 1154.0 mg.L-1,
      indicating significant differences from other main rivers in China. Na+, Ca2+,
      Mg2+, and SO42- were the major ions present in water, with mean concentrations of
      202.8, 86.0, 78.6, and 431.2 mg.L-1 respectively. Water chemistry exhibited
      distinct seasonal variations, with major ions gradually declining during the pre
      monsoon period and increasing in the post-monsoon period. An abrupt rise in
      concentrations of major ions during the ice melting interval was observed, as
      well as a sharp drop during stormy events. Dissolved loads were mainly derived
      from chemical weathering, with the contribution ratios of evaporite, silicate,
      and carbonate being 67.1%, 13.7%, and 19.2% respectively. Chemical processes
      showed different responses to climate forcing, attributed to variations in
      mineral content in the watershed and dissolution kinetics. The dominant
      contribution of evaporite in the monsoon season was due to its rapid dissolution,
      while silicate weathering increased during the pre-monsoon period, with longer
      water rock interaction times when water discharge was lower. During the post
      monsoon season, carbonate weathering was enhanced due to its high content in
      loess and due to more CO2 absorption by rain from soil. The average chemical
      weathering rates of evaporite, silicate, and carbonate were 30.6, 6.2, and 8.7
      kg.(km2.d)-1, respectively. A strong correlation between evaporite weathering
      rates and river discharge was evident; a correlation was also observed between
      carbonate weathering rates and river discharge, indicating that water discharge
      played a dominant role in chemical weathering, rather than temperature or
      precipitation.

PMID- 30188056
TI  - [Development and Evaluation of a Sustainable Long-release Carbon Material Applied
      for In-Situ Remediation of Groundwater Nitrogen Pollution].
AB  - Due to slow flow rates and inter-substance reactions in groundwater, remediation
      requires the addition of materials with sustained release properties. This
      research uses agricultural waste and zero-valent iron (Fe0), coupling biology and
      chemistry, to research and develop a sustainable long-release carbon material
      with a synergistic physico-habitat, and to evaluate its performance, also taking
      into account the occurrence of nitrogen in groundwater. The material developed
      has a double-layer structure with an inner core and an outer shell. The core,
      consisting of agricultural waste, Fe0, and other raw materials, constitutes the
      repair layer. Agricultural waste provides a carbon source for microorganisms, and
      Fe0 can quickly remove nitrate via chemical reactions and reduce DO to develop an
      anaerobic environment in water. The shell provides a solute permeation layer and
      consists of primary minerals and other components. This can slow the release of
      TOC from the core and adsorb secondary contaminants. Physical properties testing
      showed that the materials core was uniformly cross-linked, and its shell
      exhibited a clear uniform pore structure (SEM). Favorable mechanical compression
      was recorded for particle strengths of up to 80-105 N. With a density of 1.1 g.cm
      3, the material did not float in water. Experiments showed that the material had
      excellent sustained release. The amount[Max:21-25 mg.(g.L)-1] and rate[Max:0.185
      mg.(g.L.d)-1] of TOC release exhibited a steady state trend, but fluctuated
      greatly in the case of agricultural wastes[(Max amount:53-75 mg.(g.L)-1, Max
      rate:0.455 mg.(g.L.d)-1]. In terms of further functional gene abundance,
      materials leachate was found to be conducive to denitrifying bacteria. In early
      denitrification and oxygen trapping experiments, the Fe0 chemical reaction was
      dominant for reduction of nitrogen and DO, facilitating denitrification. However,
      biological denitrification gradually dominated. Differences in denitrification
      rates between iron-free and iron-containing materials were smaller, as was the
      correlation between denitrification rate and iron content. These results indicate
      the formation of physico-habitat synergistic denitrification in the materials
      system.

PMID- 30188057
TI  - [Phosphorus Forms and Distribution Characteristics in the Sediment and Soil of
      the Water-Level-fluctuating Zone in the Main Stream of the Three Gorges
      Reservoir].
AB  - Hydrological regimes changed after the Three Gorges Reservoir (TGR) became fully
      operational, with the water level fluctuating between 145 m and 175 m. This has
      altered phosphorus (P) distribution within sediments and soils of the water-level
      fluctuating zone (WLFZ). Eleven field investigations within the main stream were
      carried out in June 2016. The aim of the study was to determine lateral (sediment
      and WLFZ soil) and longitudinal variations (from the end of the backwater area to
      the Three Gorges Dam) of phosphorus species. P fractions were analyzed using a
      Standards, Measurements, and Testing (SMT) protocol. Results showed that both TP
      and NaOH-P content in sediment exhibited a clear increasing trend from the end of
      the backwater area to the Three Gorges Dam, while HCl-P declined. Average of
      totals P, OP (organic P), HCl-extracted P (HCl-P, calcium-bond P), and NaOH
      extracted P (NaOH-P, metal oxide-bound P) in sediment were (859.6+/-106.8),
      (224.6+/-113.9), (435.3+/-77.7), and (101.5+/-31.6) mg.kg-1, respectively. The
      concentration average of P species in sediment was higher than in WLFZ soil. In
      both sediment and soil, HCl-P was the main form of P, accounting for 51.3% and
      58.2% of TP, while the ratio of NaOH-P to TP was 11.7% and 8.1%, respectively. P
      fractions with a higher coefficient of variation had greater spatial
      heterogeneity.

PMID- 30188058
TI  - [Distribution Characteristics and Release Fluxes of Phosphorus Forms in Xiangxi
      Bay Sediments in the Three Gorges Reservoir Before and After Impoundment].
AB  - The sediment storage environment in tributaries has been altered by impoundment
      of water in the Three Gorges Reservoir area, affecting the distribution of
      phosphorus forms in sediment and processes at the sediment-water interface.
      Through collection of sediment and overlying water samples in Xiangxi Bay in
      August 2016 (before impoundment) and October (after impoundment), the
      distribution characteristics of sedimentary phosphorus and the environmental
      conditions of storage before and after impoundment were analyzed. Fluxes of PO43-
      P at the sediment-water interface were also estimated. Results show that pH
      increased, alkalinity and reducibility were enhanced, and Eh in sediments
      decreased after impoundment. The relative content of phosphorus in sediments
      changed as follows:NaOH-P > HCl-P > OP to HCl-P > OP > NaOH-P; this could be
      attributed to changes in the depositional environment. Compared to pre
      impoundment values, TP values after impoundment in sediment, overlying water
      rho(PO43--P), and interstitial water rho (PO43--P) were 1.3 times, 3.7 times, and
      8.3 times higher, increasing the risk of nutrient release in sediments of Xiangxi
      Bay. The manifestation of PO43--P in sendiments of Xiangxi River generally is
      "source" pre-impoundment and post-impoundment, but the PO43--P diffusive flux
      increased from -0.0029-0.0059 mg.(m2.d)-1 pre-impoundment to 0.0067-0.1071
      mg.(m2.d)-1 post-impoundment. The release of phosphorus from sediments at the
      bottom of Xiangxi Bay increased after impoundment.

PMID- 30188059
TI  - [Effect of Zirconium-modified Zeolite Addition on Phosphorus Release and
      Immobilization in Heavily Polluted River Sediment].
AB  - The effect of zirconium-modified zeolite (ZrMZ) addition on the release and
      immobilization of phosphorus in heavily polluted river sediment was investigated
      using microcosm incubation experiments. Results showed that addition of ZrMZ to
      sediment greatly reduced concentrations of P in pore water and overlying water,
      also reducing the release flux of P across the interface between overlying water
      and sediment. The addition of ZrMZ to sediment resulted in the transformation of
      NH4Cl extractable P (NH4Cl-P), Na2S2O4/NaHCO3 extractable P (BD-P), and HCl
      extractable P (HCl-P) into NaOH extractable P (NaOH-rP) and residual P (Res-P) in
      sediment, thereby leading to the reduction of mobile P (sum of NH4Cl-P and BD-P)
      in sediment. Content of bioavailable P (BAP) including water soluble P (WSP),
      readily desorbable P (RDP), iron oxide paper strip extractable P (FeO-P), and
      anion resin extractable P (Resin-P) in sediment also declined following addition
      of ZrMZ. Control of P release from sediment by ZrMZ could be due to reduction of
      P in pore water and immobilization of P in sediment. Results of this work
      indicate that ZrMZ is very promising for controlling P release from sediments in
      heavily polluted rivers.

PMID- 30188060
TI  - [Impact of Human Activities on Net Anthropogenic Nitrogen Inputs (NANI) at
      Township Scale in Erhai Lake Basin].
AB  - Excessive nitrogen inputs from human activities have become the main cause of
      water eutrophication and related ecological hazards. In order to study the impact
      of human activities on nitrogen in the basin, and based on statistical data of
      administrative units in 16 towns and villages, this study used the NANI model to
      calculate net anthropogenic nitrogen inputs (NANI) at township scale in Erhai
      Lake basin. Results show that the total amount of NANI in Erhai Lake basin was
      29.81*103 t in 2014, and nitrogen input intensity per unit area was 10986
      kg.(km2.a)-1, significantly higher than the national average. The input of
      nitrogen from food by the local tourist population was 0.26*103 t, accounting for
      8% of local food nitrogen input. Nitrogen input from chemical fertilizer is the
      largest NANI input source, accounting for 47% of net nitrogen input in the basin,
      followed by net nitrogen input of food and feed. The spatial distribution of NANI
      at township scale shows evident regionalization, with higher values in the north
      and lower values in the south of the basin. The intensity of NANI in towns with
      cropland or population is high. The corresponding risk of nitrogen pollution in
      Erhai Lake basin is therefore a primary concern, and will remain so in the near
      future.

PMID- 30188061
TI  - [Simulation of Inorganic Nitrogen Fluxes at the Sediment-water Interface in a
      Typical Intertidal Zone, Eastern China].
AB  - Taking 12 typical intertidal zones along the eastern coast of China as the
      research object, indoor tide simulation experiments were conducted to measure
      exchange fluxes of nitrate nitrogen (NO3--N) and ammonia nitrogen (NH4+-N)
      between overlying water and sediments, to investigate their spatial distribution,
      and to clarify controlling factors such as salinity, temperature, and organic
      matter. Results showed that the total NO3--N flux was -2.91-3.34 mmol.(m2.h)-1,
      while the total flux of NH4+-N was -4.36-2.34 mmol.(m2.h)-1. The average flux, at
      12C and 35C, was -0.04 mmol.(m2.h)-1, indicating that typical intertidal zone
      sediment is an effective sink for ammonia nitrogen and nitrate nitrogen. There
      was a significant difference in the spatial distribution of nitrate and ammonia
      nitrogen fluxes. At 12C, the higher the latitude, the greater the ammonia
      nitrogen flux; results for the 25 degrees -35 degrees N intertidal nitrate flux
      were as follows:<15 degrees -25 degrees N < 35 degrees -45 degrees N at 25C and
      35C, while the flux of ammonia nitrogen was 25 degrees N-35 degrees N > 15
      degrees -25 degrees N > 35 degrees -45 degrees N. The fluxes of the three
      intertidal zones decreased with increase in temperature, which controls the
      coupled nitrification-denitrification taking place in the upper layer of sediment
      and at the bottom of overlying water. NO3--N fluxes first increased and then
      decreased with temperature at 15 degrees -25 degrees N and 35 degrees -45 degrees
      N, while NO3--N fluxes at 25 degrees -35 degrees N always decreased with
      temperature. At each latitude, the higher the temperature, the lower the NH4+-N
      flux. There was no single significant effect of environmental factors on fluxes.
      Salinity, sediment organic carbon (OC), sediment total nitrogen (TN),
      concentrations of ammonia nitrogen and nitrate nitrogen in pore water, and bulk
      density synergistically affected the spatial differentiation of exchanged NO3--N
      and NH4+-N fluxes.

PMID- 30188062
TI  - [Effects of Aquaculture on Ammonia-oxidizing Prokaryotes in Sediments of Eastern
      Lake Taihu].
AB  - The abundance and diversity of ammonia-oxidizing microorganisms in sediments of
      an aquacultural area of Eastern Lake Taihu were investigated. Real-time
      quantitative PCR was used to analyze the abundance of archaeal and bacterial amoA
      genes. Cloned libraries were constructed to investigate the structure and
      diversity of the microbial community. By comparing community characteristics of
      ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB) in different
      zones, we found that:1Copy numbers of the bacterial amoA gene outnumbered those
      of archaeal amoA genes in the aquacultural zone; 2Diversity of AOA and AOB was
      higher in the aquaculture zone and control zone, respectively; 3 The dominant
      cluster of AOA and AOB in both sediments of aquiculture zone and control zone was
      Nitrosopumilus and Nitrosospira respectively. It was therefore the community
      structure of AOA (rather than AOB) in lake sediments that was affected by
      aquacultural activity.

PMID- 30188063
TI  - [Transformation of Ammonia in Wetland Sediments for Treatment of Mining
      Wastewater].
AB  - Nitrogen elements play an important role in the biogeochemical cycle of
      artificial wetlands. In this study, we investigated the anaerobic transformation
      of ammonia nitrogen and its main pathways in sediment in an artificial wetland.
      Results showed that the anaerobic ammonia oxidation (ANAMMOX) process and iron
      reduction occurred in wetland sediment, coupled with anaerobic ammonia oxidation
      (Feammox). Feammox used Fe(III) to oxidize ammonia nitrogen to produce nitrogen;
      intermediate products were nitrate, nitrite, and N2O. Addition of ferrihydrite
      promoted the Feammox process and ammonia nitrogen loss caused by Feammox was
      enhanced from 1.69 to 2.72 mg.(kg.d)-1. When ferrihydrite was added, a loss of
      28% of total nitrogen (TN) in the wetland occurred, associated with Feammox,
      increasing to 42%. Anaerobic ammonia oxidation was significantly inhibited with
      addition of ferrihydrite and TN loss in the system decreased by about 25%.
      Results showed that the formation of goethite by mineralization of ferrihydrite
      inhibited the ANAMMOX process, promoting Feammox to lead to competing electronic
      donors for the S-ANAMMOX process, causing inhibition of the S-ANAMMOX process.
      This achieves the purpose of reducing TN loss in the wetland system. In addition,
      this may have some significance for further understanding the interaction between
      iron reduction and the nitrogen cycle in the wetland.

PMID- 30188064
TI  - [Distribution Characteristics of Sulfonamide Antibiotic Resistance Genes in a
      Drinking Water Source in East China].
AB  - Antibiotic resistance genes (ARGs) in drinking water sources have attracted
      widespread attention due to the threat they pose to water security and human
      health. This study mainly focused on the distribution of sulfonamide ARGs (sul 1,
      sul 2) and one integrase gene (intI 1) in water and sediment using qualitative
      and fluorescent quantitative PCR, based on previous work on the characteristics
      of 13 kinds of sulfonamides in a drinking water source in East China. Results
      showed that the three target genes were all detected in water and sediment. The
      sul 1 gene was the sulfonamide ARG with highest concentration, with 1.5*104
      6.4*105 copies.mL-1 in source water and maximum concentration of 1.6*108 copies.g
      1 in sediment. Concentration of sul 1 was 0.6-2.2, 0.5-1.9 order of magnitudes
      higher than sul 2 and intI 1 genes, respectively. There was no significant
      difference between the absolute concentrations of sul 1, sul 2, and intI 1 in
      inflow and outflow. However, in the case of sediment, absolute abundances of sul
      1, sul 2, and intI 1 in outflow were higher than those in inflow. The maximum
      concentration of sul 1 was detected in outflow in summer (6.4*105 copies.mL-1).
      The concentration of intI 1 was higher in winter compared to other seasons. There
      was a positive correlation between sul 1 and 13 sulfonamides (r=0.69, P<0.05),
      and the relative concentration of sul 1 and amount of sulfamethoxazole were
      significantly positively related (r=0.79, P<0.01). There were also positive
      correlations between the relative concentrations of intI 1 and sul 1, sul 2
      (r:0.80 and 0.73, P<0.05), respectively, suggesting that intI 1 played an
      important role in horizontal gene transfer of sulfonamide ARGs in this drinking
      water source. This study provides basic data for monitoring pollution of ARGs, as
      well as a basis for controlling ARG pollution in the drinking water environment
      and making management decisions.

PMID- 30188065
TI  - [Distribution Characteristics of Sulfonamides and Sulfamethoxazole-Resistant
      Bacteria in Tannery Wastewater Treatment Processes].
AB  - The study investigated abundance and distribution of three sulfonamides and
      sulfonamide-resistant bacteria in the wastewater treatment processes of two
      tannery wastewater plants, as well as the extent of their removal in different
      treatment units of the plants. Results showed that the three sulfonamides were
      detected in two different tannery wastewater treatment processes, with total
      content in water samples of 59.1-706.7 ng.L-1. The content of sulfonamides in
      excess sludge samples from the two plants was 4388 ng.kg-1and 2979.4 ng.kg-1,
      respectively. Antibiotic content was therefore similar to that in municipal
      wastewater treatment plants. The three sulfonamides were removed in two different
      sewage treatment processes; both led to removal extents>70%. Antibiotic removal
      extent was relatively high in the biological unit, especially in anaerobic tanks
      (removal extent>50%). Eight strains of resistant bacteria were screened out from
      influent, effluent, and excess sludge samples of the two plants. These were
      identified as five kinds of sulfonamide-resistant bacteria. The content of
      resistant bacteria in influent and effluent was between 9.37*103-5.08*105 CFU.mL
      1and the content of sulfonamides was 1.17*107 CFU.g-1and 7.2*106 CFU.g-1in excess
      sludge samples. The removal extent of sulfamethoxazole-resistant bacteria in the
      two plants was 1.34 log and 2.15 log, respectively.

PMID- 30188067
TI  - [Substrate Flow by Different Biochemical Activities in the Urban Sewage Network].
AB  - In order to investigate the consumption mechanism of organic contaminants in
      different biological metabolism pathways within an urban sewage network, a pilot
      scale system using two kinds of sediments (urban sewage sediment and artificial
      sediment) was constructed. The pilot system was operated to study the migration
      and transformation characteristics of COD, methane, nitrate, and sulfate between
      sediment and sewage. Results showed that the variation of COD in sewage was
      170.58 mg.L-1, with change of COD by deposition and bioreaction of 101.53 mg.L-1
      and 69.05 mg.L-1, respectively. Due to biological metabolism, the generation of
      methane in sewers was of 7.39 mg.L-1; the decrease of nitrate and sulfate in
      sewage was 0.33 mg.L-1 and 21.35 mg.L-1, respectively. Based on our calculations,
      the consuming concentration of COD was 32.51 mg.L-1for methane generation, 8.04
      mg.L-1 for denitrification, and 6.41 mg.L-1for sulfate degradation by sulfate
      reducing bacteria. The decrease in COD by deposition was responsible for 65.38%
      of total variation of COD in sewage. The decrease in COD by bioreaction was
      responsible for 34.62% of total variation in COD. Meanwhile, total variation
      values of COD for methane generation, denitrification, and sulfate degradation
      were responsible for 68.01% of COD variation by bioreaction. Deposition was
      therefore the main pathway for removal of organic contaminants from the sewer
      system; biochemical activities of methane generation, denitrification, and
      sulfate degradation also played important roles.

PMID- 30188066
TI  - [Effects of Different Substrates and Particle Sizes on Wastewater Purification].
AB  - Choosing suitable substrate is key to improving the efficiency of wetland
      decontamination. However, little is known about the effect of particle size. In
      order to study the effect of substrate type and size on COD, TN, and TP removal
      from sewage, 1-2, 2-4, and 4-8 mm zeolite, 2-4, 4-8, and 8-16 mm gravel, and 2-4,
      3-5, and 6-8 mm anthracite were selected for establishment of the constructed
      system of experimental media with three replications. Results showed that removal
      efficiency of COD, TN, and TP varied with different particle sizes of the same
      material. The greatest COD removal was achieved with 4-8 mm zeolite and gravel
      and 6-8 mm anthracite, with removal rates of 53.74%, 60.76%, and 62.93%,
      respectively. Denitrification is the main pattern of nitrogen removal in the
      artificial test column; results show that smaller particle size is more effective
      for removal of TN. The removal rate of TP is also higher with smaller sizes of
      gravel and anthracite, but the opposite pattern occurred with zeolite. The
      removal of COD, TP, and TN also varied by substrate type. Anthracite led to good
      removal of COD, TP, and TN. Zeolite was most effective for removal of TN but had
      lower removal of TP. Gravel has high removal rate for COD, and has a general
      removal effect on TP.

PMID- 30188068
TI  - [Reducing Membrane Fouling from Micro-Flocculation in a Humic Acid
      Ultrafiltration Process].
AB  - This study investigated the influence of different floc morphologies produced by
      micro-flocculation process on filtration of a self-constructed polyvinylidene
      fluoride (PVDF) ultrafiltration membrane. Aluminum sulfate was used as a
      flocculant and humic acid (HA) and kaolin as raw water. Both the properties of
      flocs formed during the micro-flocculation process (floc size and distribution,
      fractal dimension) and the effects of floc formation on membrane flux under
      different conditions were investigated. The surface morphology of the
      contaminated membrane was characterized by scanning electron microscopy (SEM) and
      atomic force microscopy (AFM), and adhesion between the PVDF membrane and organic
      pollutants was measured to analyze the membrane fouling mechanism. Results showed
      that the main mechanism during a micro-flocculation process using Al3+ as a
      flocculant is electrical neutralization to remove organic matter. With an
      increase in flocculant dosage, floc size increased and the fractal dimension of
      flocs decreased. The attenuation rate of membrane flux was negatively correlated
      with floc size. The larger the floc, the lower the membrane flux attenuation
      rate, and the looser the filter cake layer formed during the ultrafiltration
      process. Comparatively, membrane fouling caused by flocs with smaller fractal
      dimension was lighter, and the membrane flux recovery rate was also higher. The
      interaction force between PVDF and organic matter was positively correlated with
      the corresponding membrane flux attenuation rate during the initial stage of
      operation. When dosage of Al3+ was 5 mg.L-1 and initial pH was 7, the HA removal
      rate was 96.7%, the membrane flux attenuation rate was lowest, and the flux
      recovery rate reached 88%.

PMID- 30188069
TI  - [Enhanced Degradation of Aniline by PS Oxidation in the Presence of UV and Ferric
      Oxalate].
AB  - Oxidative degradation of aniline by Sodium Persulfate (PS) activated with UV
      ferric oxalate[UV-Fe(C2O4)33-] was studied. The effects of Fe(C2O4)33-
      concentration, PS concentration, and pH on PS activation and aniline degradation
      were investigated. Results showed that Fe(C2O4)33- concentration and pH
      determined the reduction process of Fe3+ into Fe2+, which had significant effects
      on the oxidative degradation of aniline by PS. With an increase in Fe(C2O4)33-
      concentration, PS decomposition increased; however, when concentrations were>0.75
      mmol.L-1, aniline degradation efficiency decreased due to competition with
      oxalate ions (C2O42-) for SO4.-. Aniline degradation efficiency in processes with
      different initial Fe(C2O4)33- concentrations followed the sequence:5 mmol.L-1 <
      0.25 mmol.L-1 < 0.5 mmol.L-1 < 1 mmol.L-1 < 0.75 mmol.L-1. Neutral and alkaline
      conditions were not conducive to Fe2+ formation via photochemical reaction.
      However, with initial pH values of 7 and 9, PS activation efficiency reached 74%
      and 67% respectively after 300 min due to pH decline during the reaction; aniline
      removal efficiency was as high as 91% and 97%, respectively, higher than under
      initial acidic conditions. Furthermore, increased PS concentration was conducive
      to improvement of aniline degradation efficiency, but when PS concentration
      was>10 mmol.L-1, the aniline degradation process followed the pseudo first-order
      reaction kinetics model instead of the second-order reaction kinetics model. PS
      efficiency for aniline degradation decreased significantly due to the reaction
      between excessive PS and sulfate radicals.

PMID- 30188071
TI  - [Effects of Long-term Side Stream Extracton on Phosphorus Removal and Recovery
      Performance of EBPR System].
AB  - A sequencing batch reactor (SBR) with alternating anaerobic/oxic (An/O) operation
      was employed to investigate nitrogen and phosphorus removal performance and
      corresponding phosphate recovery effect of an enhanced biological phosphorus
      removal (EBPR) system when extracting side stream ratios of 0, 1/4, 1/3, 1/2
      anaerobic phosphorus supernatant. The operation involved three runs within 310
      days. Removal efficiencies of COD and NH4+-N were found to be relatively stable
      over the entire experimental period and effluent could meet standard A of the
      national discharge standard of pollutants for municipal wastewater treatment
      plants. Total nitrogen removal improved due to enhancement of denitrification
      capability during the anaerobic phase, and the standard-reaching rate increased
      from 88.2% to 98.6%. Although phosphate releasing capability gradually decreased,
      phosphorus removal performances of the former two runs were stable and efficient.
      The removal rate was>90% and the corresponding standard-reaching rate was>75%.
      Nevertheless, phosphorus removal performance began to fluctuate with a side
      stream ratio of 1/2 during the third run. The lowest phosphorus removal rate was
      54.2%, contributing to a 60% non-standard-reaching rate in this run. This
      suggests that long-term extraction of 1/2 side stream supernatant is not
      favorable for maintaining stable effluent of the main process. It was also found
      that long-term phosphate recovery through side stream extraction allowed
      reduction of sludge mass and had little impact on sludge settling performance. As
      a result, it is feasible to extract an appropriate side stream ratio of anaerobic
      supernatant to recover phosphate, combined with efficient removal of both
      nitrogen and phosphorus in the main process.

PMID- 30188070
TI  - [Behavior and Degradation of Polycyclic Aromatic Hydrocarbons (PAHs) in Coking
      Wastewater of A/O2 and A/O/H/O Processes].
AB  - Polycyclic aromatic hydrocarbons (PAHs) are typical organic pollutants found in
      coking wastewater, and their behavior and reduction can be affected by different
      treatment processes. Based on these considerations, this study investigated the
      behaviors of PAHs in coking wastewater under A/O2 and A/O/H/O treatment
      processes, respectively. In order to evaluate variations in PAH removal under two
      different treatment processes, samples were taken from different treatment units
      for quantification of PAHs using gas chromatography-mass spectrometry. Results
      showed that PAHs were barely degraded in anaerobic tanks of either treatment
      process and accumulated much higher concentrations than in aerobic and hydrolytic
      tanks. While low molecular weight PAHs (LMW PAHs) in aqueous phase from anaerobic
      tanks were degraded effectively in aerobic tanks, high molecular weight PAHs (HMW
      PAHs) mostly accumulated in the sludge phase; these potentially pose a higher
      environmental risk and therefore need to be treated separately. Moreover, the
      A/O/H/O process showed higher degradation of PAHs bioavailability and higher
      removal effectiveness for PAHs with four or more benzene rings than the A/O2
      process; this is attributed to the hydrolytic tank's ability to promote
      hydrolysis of macromolecular organic compounds and therefore improve
      biodegradability of PAHs. Comprehensive results from the study indicated that the
      A/O/H/O process is more advantageous for degradation of PAHs than the A/O2
      process.

PMID- 30188072
TI  - [Effect of NaCl Salinity on Extracellular Polymeric Substances and
      Bioflocculation of Anoxic Sludge in A2/O Process].
AB  - In order to improve the biological removal efficiency of nitrogen and phosphorus
      and bioflocculation performance of salt-containing wastewater, the effect of NaCl
      salinity on the efficiency of denitrification and phosphorus removal in the
      anoxic zone of an A2/O process was investigated. Fourier transform infrared
      spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) were used to
      analyze the composition and structure of extracellular polymeric substances (EPS)
      in activated sludge of the anoxic zone, to discern the effect of salinity on
      bioflocculation. Results showed that when NaCl salinity was 0-5 g.L-1,
      flocculation ability (FA) in A2/O anoxic zone was about 44% and the sludge
      particle size was 45.5 MUm. EPS content increased from 52.3 mg.L-1 to 62 mg.L-1
      and protein (PN)/polysaccharide (PS) remained at 2.1. When NaCl salinity
      increased from 10 g.L-1 to 40 g.L-1, bioflocculation of sludge significantly
      decreased. FA decreased from 40% to 22% and sludge particle size decreased from
      43.7 MUm to 32.1 MUm. EPS content increased from 76.5 mg.L-1 to 101.0 mg.L-1 and
      PN/PS decreased from 1.5 to 1.3. Based on FTIR analysis, with increase in
      salinity, the main components of EPS were always amino, amideI, and carboxyl.
      Based on XPS analysis, increasing salinity led to charge transfer of some groups
      (such as C, O, and N groups) during the interaction between EPS and Na+, but its
      form did not change.

PMID- 30188073
TI  - [Effect of Temperature and pH on Nitrogen Conversion in Feammox Process].
AB  - In recent years, the oxidation of NH4+ using Fe(III) as an electron acceptor
      under anaerobic conditions (Feammox) has received significant research attention.
      In this study, the effect of pH and temperature on nitrogen conversion during the
      Feammox process was studied through activity recovery of Feammox sludge
      acclimated by anaerobic ammonium oxidation (ANAMMOX) sludge. Results showed that
      after 40 d operation, activity of Feammox sludge was recovered. There was evident
      ammonia nitrogen conversion and total nitrogen removal from the environment, and
      the products were mainly nitrate and nitrogen. The concentration of nitrite
      remained below 2 mg.L-1. pH value and temperature significantly influenced
      nitrogen transformation during the Feammox process. With pH value of 7 and
      temperature of 30C during the Feammox process, the removal rate of total nitrogen
      was relatively high (>50%). When the pH value was 6.5, the conversion rate of
      ammonia nitrogen was 80.2%. During the Feammox reaction process, precipitation of
      iron ion compounds and coating on the sludge surface were the main interference
      factors leading to continuous operation of the reactor and exploration of the
      reaction mechanism.

PMID- 30188074
TI  - [Inhibitory Kinetics of Free Ammonia (FA) on Ammonia-oxidizing Bacteria (AOB)].
AB  - In this study, a sequencing batch reactor (SBR) was operated to investigate the
      inhibitory kinetics of free ammonia (FA) on ammonia-oxidizing bacteria (AOB). At
      the beginning of the experiment, FA concentrations in influent were altered to
      achieve stable short-cut nitrification and enrich AOB. Nitritation sludge was
      then employed to study variations in the specific nitrite production rate (SNiPR)
      during the ammonia oxidation process of batch tests. Furthermore, a kinetic model
      of FA inhibition on AOB activity was fitted for statistical analysis. Results
      showed that SNiPR increased rapidly with increase in FA concentration (0.7 mg.L-1
      <= FA <= 50.2 mg.L-1) but decreased with an increase in FA concentration (FA >=
      50.2 mg.L-1). SNiPR was maintained at 0 g.(g.d)-1 when FA concentration was
      higher than 687.1 mg.L-1, implying that AOB activity was completely inhibited.
      Statistical analysis showed that, compared to Haldane, Edwards-1#, Edwards-2#,
      and Luong inhibition kinetics models, the Aiba model was the most suitable for
      describing the inhibitory effect of FA on AOB activity. The statistical
      constants, i.e., residual square sum (RSS) correlation coefficient (R2), F value
      of the fitting equation, and confidence degree (P) were 0.005, 0.932, 181.7, and
      1.06*10-9, respectively. The dynamic constant values, i.e., maximum specific
      nitrite production rate (rmax), half saturation constant (KS), and inhibition
      constant (KI) were 0.37 g.(g.d)-1, 11.78 mg.L-1, and 153.74 mg.L-1, respectively.

PMID- 30188075
TI  - [Effect of HRT on Nitrogen Removal Using ANAMMOX and Heterotrophic
      Denitrification].
AB  - Real domestic sewage was first treated in SBR and partial nitrification was
      achieved. When average concentrations of NH4+-N, NO2--N, and COD were 37.27,
      39.97, and 120 mg.L-1, respectively, the effluent was delivered as influent of an
      anaerobic ammonia oxidation reactor (ASBR). The effect of different HRTs (36 h,
      33 h, 30 h, 27 h) on nitrogen removal of ANAMMOX and heterotrophic
      denitrification were investigated under conditions of temperature of 24C and pH
      of 7.2+/-0.2. Results showed that 1 nitrogen removal efficiency was optimum with
      HRT of 33 h. The average total nitrogen load rate(TNLR)and total nitrogen removal
      rate(TNRR)were 0.056 kg.(m3.d)-1and 0.050 kg.(m3.d)-1, respectively. The average
      effluent concentrations of NH4+-N, NO2--N, and COD were 1.36, 0.47, and 49.79
      mg.L-1, and removal rates were 96.30%, 98.83%, and 56.17%, respectively. ?NO2-
      N/?NH4+-N and ?NO3--N/?NH4+-N were 1.17 and 0.15, 0.15 and 0.11 less than
      theoretical ANAMMOX values (1.32, 0.26) due to heterotrophic denitrification. 2
      The contribution of ANAMMOX to nitrogen removal decreased; however, the
      contribution of heterotrophic denitrification to nitrogen removal gradually
      increased with decreasing HRT. This provides a point of reference for ANAMMOX in
      engineering applications.

PMID- 30188077
TI  - [Analysis of Characteristics and Sources of Heavy Metals in Farmland Soils in the
      Xijiang River Draining of Guangxi].
AB  - In order to determine the distribution characteristics of heavy metal pollution
      in farmland soils and related influencing factors in the Xijiang River Basin,
      2187 farmland soil samples were collected and their heavy metal contents were
      tested. The spatial structure and distribution characteristics of heavy metal
      elements were studied using a combination of geostatistics theory and GIS spatial
      interpolation. The potential ecological risk index was employed for risk
      assessment. Multivariate statistical methods, such as correlation analysis and
      principal component analysis, were used to analyze heavy metal sources. Results
      showed that farmland soils in the Basin were enriched with seven kinds of heavy
      metal to some extent, with Cd accumulation being the most evident. T-test
      independent samples results showed significant differences in heavy metal content
      between dry and field paddy soils (P<0.05). Cd content in paddy soils was
      significantly higher than in corresponding dry land soils. Cd in farmland soils
      in Xijiang River exhibited higher potential ecological risk. Correlation analysis
      and principal component analysis showed that enrichment of Pb, Zn, As, Cd, and Cu
      in soil was due to anthropogenic factors such as mining activities, traffic, and
      sewage irrigation, while Ni and Cr were influenced by natural factors, such as
      soil parent material. High-content areas of As, Cd, Pb, Zn, and Cu in the upper
      reaches of the basin are all distributed in the Diaojiang River basin and the
      Dahuanjiang River basin. Cd was most widely distributed. The most intensive
      sampling sites indicated that mining activities have caused some degree of heavy
      metal pollution in local farmland soils.

PMID- 30188076
TI  - [Reactivation Performance of Nitrosation Flocculent Sludge After Long-term
      Storage].
AB  - In order to explore the nitrogen removal performance of nitrosation flocculent
      sludge subject to long-term storage, nitrosation flocculent sludge which had been
      stored at 4C for ten months was inoculated in a continuous stirred tank reactor
      (CSTR) to investigate its activity recovery performance. MiSeq high throughput
      sequencing technology was also employed to analyze the structure of the microbial
      community before and after reactivation. Results showed that, under DO control of
      DO 0.4-0.8 mg.L-1, pH value of about 8 and temperature of (30+/-1)C, the sludge
      could be reactivated in 15 days. Both the removal efficiency of ammonia nitrogen
      and the accumulation ratio of nitrite nitrogen were higher than 90%. The color of
      the sludge quickly changed from grey at early inoculation to brown, while the
      sludge volume index (SVI) quickly decreased and both mixed liquor volatile
      suspended solids (MLVSS)/mixed liquor suspended solids (MLSS) and extracellular
      polymer substances (EPS) significantly increased. With the recovery of
      nitrosation performance, anaerobic and heterotrophic bacteria were washed out,
      the relative abundance of ammomia-oxidizing bacteria such as Nitrosomonas
      significantly increased, while the growth of nitrite-oxidizing bacteria such as
      Nitrospria was selectively inhibited. Nitrosation flocculent sludge could be
      inoculated after long-term storage to achieve rapid start-up of partial
      nitrification and allow practical application of partial nitrification processes.

PMID- 30188078
TI  - [Soil Organic Carbon of Purple Soil as Affected by Different Application of
      Biochar].
AB  - Soil organic carbon (SOC) is the most important part of the soil carbon pool and
      soil labile organic carbon is a key indicator of changes in the soil carbon pool.
      In order to study changes in SOC and its labile components with different biochar
      additions to soil, a field experiment was conducted at Chongqing National Purple
      Soil Fertility and Fertilizer Efficiency of Long-Term Monitoring Station.
      Different amounts of biochar (0 kg.hm-2, CK; 4000 kg.hm-2, 0.5 BC; 8000 kg.hm-2,
      BC; 16000 kg.hm-2, 2BC) combined with fertilizer were applied to purple soil in
      this hilly area. SOC and soil labile carbon content were determined for purple
      soil rape-maize rotation systems. Results showed that:1 Application of biochar
      can significantly improve SOC content; within a certain range, the amount of
      added biochar is correlated with SOC content. The content of soil microbial
      biomass carbon (SMBC) increased with application of 8000 kg.hm-2 biochar, but
      decreased with application of 4000 and 16000 kg.hm-2. The content of dissolved
      organic carbon (DOC) and readily oxidized carbon (ROC) in soil increased with
      different amounts of biochar; the highest DOC (198.83 g.kg-1) and ROC (4.86 g.kg
      1) were obtained under low biochar addition treatments. 2 The application of
      biochar significantly decreases the ratio of soil ROC to SOC and microbial
      entropy. The ratio of soil ROC to SOC and microbial entropy of 0.5 BC treatment
      are 20.45% and 4.11%, respectively, lower than for CK. Moreover, 0.5 BC and BC
      treatments can significantly improve the ratio of soil DOC to SOC. In summary,
      biochar addition in soil leads to low soil microbial activity but higher soil
      stability. An appropriate biochar treatment can stimulate accumulation of SOC,
      and 0.5BC treatment can improve soil DOC and ROC.

PMID- 30188079
TI  - [Effects of Straw and Biochar Addition on Soil Carbon Balance and Ecological
      Benefits in a Rape-maize Rotation Planting System].
AB  - The effects of different straw and biochar applications on the carbon balance of
      a farmland ecosystem were studied under a rape-maize rotation planting system.
      The study explored impact of straw and biochar addition on soil carbon
      sequestration. A field experiment was carried out at the National Monitor Station
      of Soil Fertility and Fertilizer Efficiency of Purple Soils (Chongqing, China).
      Five treatments, i.e., control (CK, no organic material), straw only (CS), straw
      and microorganism (CSD), half straw and half biochar (CSBC), and biochar only
      (BC), were applied. In-situ cumulative emissions of soil total carbon were
      subsequently monitored. Based on field experiment and survey data, carbon
      emissions, carbon sequestration, and and economic and environmental benefits were
      analyzed for soil respiration, soil carbon pool, crop carbon pool, as well as the
      cost of agricultural inputs after straw and biochar application. The main results
      were:1Accumulative emissions of soil carbon during two planting seasons were all
      higher with treatment than in CK, and the differences between CS, CSD, and CK
      were significant (P<0.05). 2Compared with CK, both straw and biochar treatments
      increased crop yield (by 1.49%-3.92%) and crop net primary productivity (NPP)
      increased by 4.44%-17.90%. Largest yields and NPP during both seasons were
      achieved with CSD.3Net carbon sequestration was positive during both seasons in
      all treatments without CK, indicating a carbon sink effect. The highest net
      carbon sequestration was obtained with CSD (9.05 t.hm-2) and BC (10.75 t.hm-2)
      treatments. The lowest carbon emissions were obtained with the BC treatment, with
      emissions 62.69%-81.86% lower than CK. 4The highest production to cost ratio was
      obtained with CS treatments during the rape planting season. Application of only
      biochar reduced the production to cost ratio but increased the carbon trading
      income (466.95-561.22 yuan.hm-2).5BC treatment increased carbon productivity (CP)
      in both seasons, while the economic (CJ) and ecological benefits(CE) of BC
      treatment were significantly lower than with other treatments. The addition of
      straw increases economic and ecological benefits; however, addition of biochar
      reduces such benefits.

PMID- 30188080
TI  - [Potential to Ensure Safe Production from Rice Fields Polluted with Heavy Cadmium
      by Combining a Rice Variety with Low Cadmium Accumulation, Humic Acid, and
      Sepiolite].
AB  - The study investigated the potential of ensuring safe production of rice from
      paddy fields affected by heavy cadmium contamination. A paddy soil polluted with
      heavy cadmium (total Cd content of 2.52 mg.kg-1) surrounding a lead-zinc mining
      area in Guiyang County of Chenzhou City, Hunan province was selected for
      analysis. We investigated production using a low cadmium accumulation rice
      variety (Oryza sativa L. Jia-33) and passivation additives for heavy metal
      activity (including humic acid and sepiolite). Results showed that:Oryza sativa
      L. Jia-33 showed good low cadmium accumulation characteristics in rice fields
      with heavy cadmium pollution. When humic acid and sepiolite were applied (alone
      or combined), the accumulation of Cd in different organs of the rice declined,
      and the transport coefficient of Cd for stem to root and polished rice to stem
      also declined. The rate of decline increased with increased application dosage.
      The cadmium content in polished rice was lower than the limit established in the
      National Food Safety Standard (GB 2715-2012), when applying 5.250 t.hm-2 humic
      acid, 6.750 t.hm-2 sepiolite, or a combination of 1.125 t.hm-2 humic acid and
      3.37 5 t.hm-2 sepiolite; Cd content in polished rice was (0.171+/-0.01), (0.184+/
      0.01), and (0.181+/-0.01) mg.kg-1, respectively. Single or combined application
      of humic acid and sepiolite promoted the transformation of soil Cd to residual
      and Fe Mn oxide bound forms, significantly reducing the content of available Cd
      and the bioavailability of Cd in soil, and further reducing Cd content in all
      rice organs. The reduction was more effective with single application of
      sepiolite or combined application of humic acid and sepiolite. The effects of
      combined application of humic acid and sepiolite were also more beneficial for
      soil nutrients, while soil available phosphorus, available potassium, phosphorus,
      and organic matter content increased with increased application of amendments.
      Soil nitrogen content did not change. In conclusion, results indicate that joint
      application of humic acid, sepiolite, and a low Cd accumulation rice variety are
      best for safe production on heavy cadmium-contaminated soil.

PMID- 30188082
TI  - [Effects of Different Levels of Irrigation with Reclaimed Water on Soil Enzyme
      Activity and Distribution of Thermotolerant Coliforms].
AB  - This study aimed to discern the effect of different levels of irrigation with
      reclaimed water on soil enzyme activities and on the distribution of
      thermotolerant coliforms. The effects of two irrigation water qualities
      (reclaimed water and tap water) and two irrigation levels (full irrigation and
      insufficient irrigation) on soil enzyme activity and distribution of
      thermotolerant coliforms were studied through indoor soil column irrigation.
      Results indicated that:1 Reclaimed water irrigation increased soil urease and
      invertase activity compared with tap water under the same irrigation conditions.
      Compared with insufficient irrigation with reclaimed water, full irrigation with
      reclaimed water significantly increased soil invertase activity and deep soil
      catalase activity. 2 At the same irrigation level, the number of thermotolerant
      coliforms in soil significantly increased with reclaimed water irrigation. The
      number of thermotolerant coliforms in soil under full irrigation with reclaimed
      water was significantly higher than with insufficient irrigation using reclaimed
      water. The number of thermotolerant coliforms in surface soil of the four
      irrigated treatments was significantly higher than in the deep soil layer, and
      with progression of irrigation, the number of thermotolerant coliforms in the 0
      60 cm soil layer decreased. 3 There was a significant positive correlation
      between the quantity of thermotolerant coliforms and the activity of soil urease
      and invertase, and between the quantity of thermotolerant coliforms and the
      activity of soil catalase. Reclaimed water therefore promoted enzyme activity
      that can promote transformation of C and N in soil. Reasonable irrigation with
      reclaimed water can therefore effectively control the number of thermotolerant
      coliforms in soil.

PMID- 30188081
TI  - [Interactive Effects of Ozone and Drought on Antioxidant Enzyme Activities of
      Poplar Leaves].
AB  - Ground-level ozone (O3) pollution and drought have become major environmental
      factors that threaten the normal growth of plants. In this study, we determined
      the effects of three O3 concentrations (charcoal-filtered air, CF, non-filtered
      air, NF and non-filtered air+40 nmol.mol-1, NF40), two water treatments (well
      watered, WW, and mild drought, MD, 60% of WW in volumetric soil water content),
      and their interactions on the light-saturated photosynthesis rate (Asat) and on
      the activity of antioxidant enzymes and soluble proteins of the poplar '546'
      (Populus deltoids cv. 55/56*P. deltoides cv. Imperial). Results showed that Asat
      significantly decreased with elevated O3, and with interactions between O3 and
      drought. Drought significantly reduced the activities of catalase (CAT) and
      superoxide dismutase (SOD) but did not affect the activities of peroxidase (POD)
      or ascorbate peroxidase (APX). Reduction ranges in CAT and SOD increased with
      drought duration. APX activity significantly decreased with increasing O3 and
      drought, but soluble protein content did not. Activities of antioxidant enzymes
      were not significantly affected by elevated O3 and their interactions. Results
      provide a scientific basis for protection of poplar plantations in response to
      increasing O3 concentrations and drought under environmental changes.

PMID- 30188083
TI  - [Characteristics of Heavy Metals in Chicken Manure Organic Fertilizers in the
      Huang-Huai-Hai Region and related Environmental Risk Assessment].
AB  - One hundred and twenty types of chicken manure organic fertilizer samples were
      collected from five provinces and two cities in the Huang-Huai-Hai region, to
      investigate heavy metal content, fractionation, and environmental risk through
      toxicity characteristic leaching procedures. Results showed that content of heavy
      metals in chicken manure organic fertilizer varied greatly, in the order of Zn >
      Cu > Pb > As > Cd. When compared with the standard for organic manure, ratios of
      Cd, As, and Pb exceeded the standard by 6.7%, 47.05%, and 14.28%, respectively.
      Moreover, the content of heavy metals varied significantly in different
      provinces. Cd and Zn in organic manure fertilizers were mainly Fe and Mn oxide
      bound fractions, accounting for 37.3% and 43.79%, respectively. However, the
      proportion of residual fractions of Pb, organically-bound fractions of Cu, and
      exchangeable forms of As were higher. Contents of TCLP-Zn,-Cu,-Cd,-Pb and-As in
      organic manure were 41.11, 33.3, 0.07, 1.25, and 0.21 mg.kg-1, respectively. The
      number of samples in which Zn and Pb in organic manure exceeded the standard was
      6 and 5, respectively, with these mainly obtained from Hebei and Jiangsu
      provinces. There was a significant correlation between total content of Zn, Cu,
      Cd, and As in organic manure and content of TCLP (P<0.05). Based on an annual
      manure application rate of chicken manure of 15 t.hm-2, safe application of
      chicken manure is in the order of Henan > Tianjin > Anhui=Shandong=Jiangsu >
      Hebei > Beijin.

PMID- 30188084
TI  - [Heavy Metal Content of Rural Living Solid Waste and Related Source and
      Distribution Analysis].
AB  - Living solid waste of 72 typical villages and towns in 12 provinces was
      investigated, and related heavy metal pollution characteristics, source, and
      distribution were analyzed. Results showed that heavy metal content of As, Hg,
      Pb, Cd, Cr, Cu, Zn, and Ni in living solid waste of typical northern villages of
      China was (7.51+/-8.89), (0.64+/-0.42), (21.91+/-12.29), (4.82+/-8.37), (86.36+/
      59.99), (36.43+/-15.98), (62.19+/-36.61), and (46.07+/-25.22) mg.kg-1,
      respectively. Content of As, Hg, Pb, Cd, Cr, Cu, Zn, and Ni in living solid waste
      of typical southern towns was (7.43+/-8.82), (0.83+/-0.74), (21.62+/-13.76),
      (1.84+/-4.55), (131.06+/-74.96), (37.20+/-16.80), (98.04+/-63.71), and (46.75+/
      25.75) mg.kg-1, respectively. Cd and Hg exceeded the standards for urban garbage
      agricultural control and soil environmental quality. Sources of heavy metals in
      domestic waste were explored by Pearson correlation analysis, cluster analysis,
      and principal component analysis. Results showed that Pb and Cd were mainly
      derived from kitchen waste, dust, paper, rubber, and plastic. Hg was mainly from
      kitchen waste and dust. Zn and Cr were mainly from dust. Cu was mainly from dust,
      paper, rubber, plastic, battery, and electronic waste. Ni was mainly from battery
      and electronic wastes. As was mainly derived from pesticides and fertilizers.

PMID- 30188085
TI  - Impact of socio-economic development, contact and peer counselling on stigma
      against persons affected by leprosy in Cirebon, Indonesia -a randomised
      controlled trial.
AB  - Objectives: People affected by leprosy are often stigmatised, but stigma is
      rarelyquantified and the effectiveness  of interventions is often not evaluated.
      The SARIProject aimed to test and evaluate three interventions: counselling
      (involving peercounsellors), socio-economic development (SED) and contact between
      communitymembers and affected people. Results: This  study  used  a  controlled 
      trial  design  in  which  pairs  of  the  stigma-reduction interventions were
      randomly allocated to sub-districts in Cirebon District,Indonesia. The study
      sample consisted of one cohort of people affected by leprosy (on treatment or
      treated) and two independent samples of community members. The latter were 
      selected  through  purposive  sampling. Three  scales  (e.g.  SARI  Stigma 
      Scale,Participation  scale)  were  applied  among  leprosy-affected  people  and 
      two  scales(e.g.  Social  Distance  Scale)  were  used  among  community  members
      pre-  and post-intervention.  Among  affected  people  (n=237),  significant 
      differences  in reduction of stigma and participation restrictions were found in
      all intervention areas and an improvement in quality of life in some intervention
      areas. Social distance and social stigma significantly reduced among community
      members (n=213 and 375) in the two intervention areas where the contact
      intervention was implemented. Two of the five instruments indicated changes in
      the control area, but the changes in the intervention areas were much larger.
      Conclusion: The  SARI  Project  has  demonstrated  that  a  measurable  reduction
      inleprosy-related stigma can be achieved, both at community level and among
      peopleaffected by leprosy, using reproducible interventions that can be adapted
      to differentsettings and target groups.

PMID- 30188086
TI  - Cultural validation of a new instrument to measure leprosy-related stigma: the
      SARI Stigma Scale.
AB  - Background: There is a need for comprehensive, valid and reliable instruments to
      assess leprosy-related stigma. This paper presents the process of the cross
      cultural validation  of  an  instrument  in  Cirebon  District,  Indonesia 
      initiated  by  the  Stigma Assessment and Reduction of Impact (SARI) project.
      Methods: The  Berger  Scale  was  initially  developed  to  assess  HIV/AIDS
      relatedstigma.   This   study   explores   the   conceptual,   item,   semantic, 
      operational   andmeasurement equivalence of this scale for leprosy. The process
      included a qualitativestudy, translation and back-translation, training of
      interviewers, a pilot and the maindata  collection.  We  aimed  for  a  sample 
      of  154  people  affected  by  leprosy  with60 repeat interviews. They were
      selected through convenience sampling. Results: The   original   scale   showed  
      acceptable   conceptual   equivalence,   butinsufficient  item,  semantic  and 
      operational  equivalences.  For  instance,  there  wereirrelevant HIV-related
      items and the respondents found it difficult to indicate theirlevel  of 
      agreement  with  the  given  statements.  Major  adjustments  were 
      necessary,leading to a new version of the scale. The measurement properties of
      the new versionshowed good internal consistency (Cronbach's alpha 0.88); no floor
      or ceiling effects;and a good reliability (intra-class correlation coefficient
      0.75).

PMID- 30188088
TI  - Assessment of stigma among people living with Hansen's disease in south-east
      Nigeria.
AB  - Objectives: The purpose of this study was to assess the stigma situation in
      Hansen's disease from the perspective of both people affected by Hansen's disease
      and those living in the surrounding community in southeast Nigeria. Design: A
      cross-sectional survey was conducted among affected people and non-affected
      people using the xplanatory model interview catalogue stigma scale for the
      community  adjusted  for  leprosy  and  for  leprosy  patients,  internalised 
      stigma  of mental illness scale adjusted for leprosy, Participation Scale and the
      Social distancescale.   Data   obtained   were   analysed   using   descriptive  
      statistics   of   frequency, distribution  tables,  mean  and  standard 
      deviation  as  well  as  inferential  statistics  of Mann-Whitney  U  test, 
      Kruskal-Wallis  H  test  and  Spearman  rho  correlation  rank. A total of 434
      participants including 63 affected people and 371 community members all within
      the age range of 12 - 89 years participated in this study. Result: The perception
      of stigmatisation was higher in single participants, female participants, cooks,
      traders, crafts people and participants with primary and secondary school
      certificates, while beggars recorded the least perception of stigmatisation. The
      outcome of this study showed that females living in the community had a higher
      tendency of keeping a social distance than males. It also showed that on average,
      severe  participation  restrictions  were  found  among  people  with  WHO 
      disability Grade  II,  traders,  males,  beggars,  married  people  and  those 
      without  any  formal education while crafts people did not have significant
      participation restrictions. Conclusion: There is an urgent need to intensify the
      stigma reduction strategies and the necessary rehabilitation support. A
      standardised instrument should be developed to monitor the efficiency of such
      programmes.

PMID- 30188087
TI  - ENDOTELIAL-DEPENDENT OF THE REGULATION OF ANGIOGENESIS.
AB  - The review presents cellular and molecular mechanisms regulating angiogenesis. In
      response to the angiogenesis inducers impact the activated endothelial cells and
      their precursors (progenitor cells) synthesize and produce angiogenic molecule
      that differ by chemical origin and biological functions but all of them enable
      these cells to influence both directly and indirectly on new vessels growth.
      Among the great number of angiogenic molecules the scientists hold interests in
      the following: the set of vascular endothelial growth factors, the set of the
      fibroblast growth, transforming growth factor, tumor necrosis factor and some
      other soluble polypeptides which occurred to be an effective regulators of
      angiogenesis. However, despite the evident achievements in studies of cellular
      and molecular mechanisms of angiogenesis it is still difficult to control this
      process. Therefore the main goal of the study was to review endothelial-dependent
      factors and mechanisms of capillary vessels growth regulation.

PMID- 30188089
TI  - TUMOR MICROENVIRONMENT REGULATION BY HYPOXIA-INDICIBLE FACTORS (HIFs), AND p53
      FAMILY PROTEINS.
AB  - Except affecting cancer cells, hypoxia and HIF-dependant signaling lead to
      changes in tumor microenvironment, which plays an important role in cancer
      progression. Tumor microenvironment modification can influence the immune
      response, tumor growth and metastases. On the other hand it is well known that
      more than half cases of all cancers are characterized by mutation in the gene
      encoding tumor suppressor p53. Inactivation of p53 is necessary for cancer
      progression on the late stages. Therefore an existence of reciprocal regulation
      between HIF proteins family and p53 proteins family may be an important factor
      determining course of disease. In this review we attempt to make a general
      picture of changes that take place in different components of tumor
      microenvironment in response to hypoxia and HIFs and impact of the p53 family
      genes on these processes.

PMID- 30188090
TI  - CHARACTERISTICS OF TUMORS THAT DEVELOPED IN MICE AFTER TREATMENT WITH IRRADIATED
      SYNGENEIC MESENCHYMAL STEM CELLS OF BONE MARROW.
AB  - Mesenchymal stem cells (MSCs) are present in almost all organs and tissues of the
      organism. It is believed, that MSCs could be transformed into cancer stem cells
      spontaneously or under influence of genotoxic factors and trigger the growth of
      tumors. The aim of this work was to study the possibility of malignant
      transformation of cultured MSCs from murine bone marrow (MSCs-BM) after g
      irradiation in vitro and characterize of biochemical and histological features of
      the tumors that developed after transplantation of MSCs-BM into syngeneic mice.
      Tumors were observed in 3-4 months after MSCs-BM transplantation. After
      administration of MSCs-BM irradiated at a dose of 1 Gy, tumors were seen in 2 of
      5 mice. After transplantation of MSCs-BM irradiated at a dose of 6 Gy, tumors
      were found in all 5 of 5 mice. In the case of control MSCs-BM, only one tumor
      appeared in 6 months after transplantation. The telomerase activity was two times
      higher in the tumor developed from 6 Gy irradiated MSCs-BM than from 1 Gy
      irradiated MSCs-BM. The tumors developed from control and irradiated MSCs-BM were
      classified as multicomponent mesenchymomas ("mixture of sarcomas"). Histological
      examination showed that tumors contained tissue areas of different histogenesis.
      Thus, MSCs-BM g-irradiated at doses of 1 and 6 Gy and, much less frequently,
      control MSCs-BM can transform into tumor cells and induce development of
      multicomponent mesenchymomas.

PMID- 30188091
TI  - EFFICACY OF MESENCHYMAL STEM CELLS USED FOR THE IMPROVEMENT CEREBRAL
      MICROCIRCULATION IN SPONTANEOUSLY HYPERTENSIVE RATS.
AB  - Elaboration of new methods of correction of microcirculatory disorder in the
      brain caused by persistent high blood pressure is a topical task both for
      medicine and for biology. We studied influence of intracerebral transplantation
      of human mesenchymal stem cells (MSCh) to cerebral microcirculation in young (4
      months) and aged (12 months) spontaneously hypertensive rats (SHR). It was shown
      that transplantation MSCh promoted the rise of the density of microvascular
      network of young SHR ca. 1.6-fold; density of the arteriolar area of
      microvascular network of the pia mater increased ca. 1.9-fold. The density of
      microvascular network of aged SHR increased ca. 1.4-1.5-fold after
      transplantation MSCh. The perfusion and tissue saturation of sensorimotor cortex
      of young SHR increased to the level of young normotensive rats, and in aged SHR
      the perfusion and tissue saturation of sensorimotor cortex was not increased.
      Conclusion: the intracerebral transplantation MSCh almost completely leveled the
      pathological changes of the microcirculation in the sensorimotor cortex of the
      brain of young SHR and improved unimportantly microcirculation in aged SHR.

PMID- 30188092
TI  - Stigmatisation and discrimination: Experiences of people affected by leprosy in
      Southern Ghana.
AB  - Introduction: Leprosy, a chronic infectious disease, poses a serious public
      health concern due to its impact on the wellbeing of affected people. This study,
      which was set in Ghana, explored stigmatisation and discrimination experiences of
      people affected by leprosy resident at the Weija Leprosarium in Accra.
      Methodology: Using a qualitative research methodology, 26 participants were
      purposively selected and in-depth interviews conducted. The interviews were audio
      recorded, transcribed, and categorised based on the objectives of the study.
      Findings: The findings revealed that participants experienced stigma and
      discrimination from their families, friends, healthcare providers and community
      members. Evidence showed that whereas some participants anticipated stigma and
      discrimination from prospective employers, others internalised the negative
      beliefs associated with the disease and gave up searching for jobs. Moreover, the
      findings indicated that participants were not willing to reintegrate into their
      communities since they considered the Leprosarium a safe haven. Conclusion: Based
      on the findings of the study, we conclude that people affected by leprosy
      included in this study experienced stigmatisation and discrimination. We
      therefore suggest that efforts aimed at reducing and in the long run curing the
      stigma of leprosy must be contextualised and scaled up. Also, implications are
      discussed for social work and public health practices.

PMID- 30188093
TI  - ROLE OF Wip1-p53 AXIS IN RESPONSE OF MURINE CELLS TO TREATMENT WITH SODIUM
      BUTYRATE AND MEK/ERK SIGNALLING PATHWAY INHIBITOR.
AB  - The use of histone deacetylase inhibitors and inhibitors of MEK/ERK-pathway is
      proposed as a novel potential approach in cancer treatment. Here we studied the
      effects of histone deacetylase inhibitor, sodium butyrate, and MEK/ERK-pathway
      inhibitor, PD0325901, on cells with modifications in genes involved in anti
      cancer therapy response, Wip1 phosphatase and p53. We have investigated the
      effect of these agents on cell cycle of wild-type cells, Wip1 knockout cells and
      cells with double deletion of Wip1 and p53. Our results showed that more severe
      changes in S and G2/M phases were observed in response to sodium butyrate in Wip1
      defecient cells than in wild-type cells. Meanwhile, PD0325901 treatment led to G1
      arrest. At the same time, a "sodium butyrate type" response dominated the
      response to combined treatment with both drugs in Wip1-deficient cells, while the
      response of Wip1-/-/p53-/- cells to combined treatment was similar to the single
      use of PD0325901. Wip1-/- and Wip1-/-/p53-/- cells were more sensitive to the use
      of PD0325901 than wild-type cells. Obtained results suggest that Wip1 deficiency
      sensitizes cells to sodium butyrate and to MEK/ERK inhibitors independently from
      Wip1 main target protein - p53. Data acquired give insights into role of Wip1 in
      cellular responses to treatment with HDAC and MEK/ERK inhibitors.

PMID- 30188094
TI  - HETEROGENEITY OF COILIN-CONTAINING NUCLEAR DOMAINS IN EARLY MOUSE EMBRYOS.
AB  - The nucleus of mouse two-cell embryos houses the coilin-containing bodies of two
      types: 1) 1-3 large spherical structures of 1 mm and 2) small foci, which vary in
      number in different blastomeres. The largest coilin-containing structures, unlike
      the smallest ones, contain RNA polymerase I, nucleic acid chaperon YB-1, and also
      actin. Neither large nor small coilin-positive domains contain symplekin, one of
      the signature components of histone locus bodies. In the nuclei of late two-cell
      embryos, symplekin localizes to 1-2 well-formed roundish bodies that are observed
      both in close proximity to the coilin-positive structures and far away from them.
      Large coilin-containing bodies were not observed in embryos at the morula stage
      as well as in the nuclei of late two-cell embryos after artificial suppression of
      transcription activity. Thus, a population of coilin-containing bodies in the
      nuclei of late two-cell embryos of mice is heterogeneous in morphology and
      molecular composition. It could be assumed that the largest coilin-containing
      bodies are provisional nuclear domains that are formed at the background of
      significant changes of nuclear metabolism at the final stages of embryonic genome
      activation and the initial stages of reactivation of nucleolar transcription.

PMID- 30188095
TI  - Knowledge, Attitudes and Practices relating to Leprosy among Public Health Care
      Providers in Colombo, Sri Lanka.
AB  - Introduction: Leprosy remains a serious public health problem due to its ability
      to cause disability. The prevention of leprosy ultimately lies in the early
      diagnosis and treatment of the individuals having leprosy, thereby preventing
      further transmission. In Sri Lanka, 46% of new cases identified in year 2013,
      were late presentations andthis caused to 7-8% patients to present with
      deformities. It has been observed that lack of awareness among health staff has
      contributed to this late diagnosis. Objective: To describe knowledge, attitudes
      and practices towards leprosy amongst public health care workers in Colombo
      Municipal Council area, Sri Lanka. Material and Methods: A  descriptive  cross 
      sectional  survey  was  carried  out  in Colombo  Municipal  Council  area  by 
      distributing  self  administered  questionnaire among all public healthcare
      workers (n=178) from January to February, 2015. Results: Hundred  and  fifty 
      three  participants  (86%)  identified  'hypo  pigmented patches',  64  (36%)
      identified  'skin  nodules'  and  36  (20%)  identified  'thickened nerves' as
      suspicious sings of leprosy. More than one fifth of participants believed leprosy
      is easily transmitted by touch. Sixty one (34.3%) health care workers werescared
      of leprosy and 77 (43.3%) didn't want to reveal to a friend that if a family
      member  gets  leprosy.  Another  49  (27.5%)  didn't  want  to  share  materials
      with a patient. A significant minority (22.5%) believed that patients should be
      kept apart from others. Conclusion: Including  leprosy  in  continuous  medical 
      education  and  refresher training  is  crucial  in  early  diagnosis  of 
      leprosy  as  certain  gap  in  knowledge  was identified. An emphasis needs to be
      placed on education regarding transmission and low  rate  of  infectivity  of 
      leprosy  as  study  revealed  certain  misconceptions  and prejudices still exist
      even among healthcare workers.

PMID- 30188096
TI  - PRODUCTION OF SINGLE CHAIN FRAGMENT VARIABLE (scFv) ANTIBODY AGAINST PARANOSEMA
      LOCUSTAE ALPHA/BETA-HYDROLASE AND IMMUNOLOCALIZATION OF MICROSPORIDIAN ENZYME IN
      THE INFECTED HOST CELL.
AB  - Microsporidia is a widespread group of fungi-related intracellular parasites.
      Direct contact of the most microsporidia species with host cytoplasm suggests
      that these parasites may control physiological processes of infected cells by
      secretion of various proteins. In previous experiments, secretion of significant
      amounts of microsporidia Paranosema locustae alpha/beta-hydrolase into infected
      cells of Locusta migratoria fat bodies was demonstrated using polyclonal
      antibodies against the enzyme. However, heterologous expression of microsporidian
      hydrolase in yeast Pichia pastoris cells was not accompanied by its secretion. In
      this study, we have constructed library of recombinant single chain antibodies
      (scFv-fragments) against proteins of fat bodies of infected locusts and isolated
      mini-antibody specifically recognizing the studied enzyme using phage display
      technology. Immunoblotting and immunofluorescent microscopy with selected scFv
      fragment confirmed secretion of two different in size forms of P. locustae
      alpha/beta-hydrolase into infected host cell. Prospects of scFv-fragment use to
      explore the role of microsporidian hydrolase in host-parasite relations and
      mechanism of its secretion are discussed in the paper.

PMID- 30188097
TI  - AGGREGATION BY LECTIN-METHODICAL APPROACH FOR EFFECTIVE ISOLATION OF EXOSOMES
      FROM CELL CULTURE SUPERNATANT FOR PROTEOME PROFILING.
AB  - Exosomes are small membrane vesicles secreted by most cell types in vivo and in
      vitro. Exosomes are found in cell culture media, blood, urine, amniotic fluid,
      malignant ascite fluids and contain distinct subsets of microRNAs and proteins
      depending upon the tissue from which they are secreted. Thus exosomes constitute
      potential biomarkers of human diseases, such as cancer. A major bottleneck in the
      development of exosome-based diagnostic assays is the challenging purification of
      these vesicles; this requires time-consuming and instrument-based procedures.
      Isolation of exosomes can be a tedious, non-specific, and difficult process.
      Here, we provide a preparative technique for isolation of exosomes based on their
      ability to aggregate in the presence of lectins. The new method for lectin-based
      isolation of exosomes from cell culture media was developed as a sample
      preparation step for exosome-based protein biomarker research.

PMID- 30188098
TI  - GENOTOXIC EFFECT OF USNIC ACID ENANTIOMERS IN VITRO IN HUMAN PERIPHERAL BLOOD
      LYMPHOCYTES.
AB  - Cytotoxic and genotoxic effect of (+) and (-) enantiomers of usnic acid in human
      peripheral blood lymphocytes studed. We have shown that the studied usnic acid
      enantiomers in concentrations of 0.04-0.30 mM have a pronounced cytotoxic effect.
      We have found that the enantiomers of usnic acid in concentrations 0.04-0.30 mM
      exhibit genotoxic effect. Genotoxicity of (-)-usnic acid enantiomer in
      concentrations of 0.15 and 0.30 mM was in 2 times higher than hat of the (+)
      enantiomer. It has been noted that (+) and (-) usnic acid enantiomers induce
      atypical "comets" (hedgehogs). Wherein, (-)-usnic acid induced to 2.5-3.5 times
      more atypical "comets" than its (+) enantiomer.

PMID- 30188099
TI  - IMMUNOHISTOCHEMICAL STUDY OF DEPIGMENTED SKIN OF VITILIGO PATIENTS.
AB  - Immunohistochemical analysis was used to study depigmented skin areas such as
      macular of depigmentation and skin perimakular areas in vitiligo patients. It has
      been shown that the cells containing melanocytic cell marker TRP1 are localized
      both in macular and perimakular areas. Within the macula of depigmentation all
      TRP1 positive cells are in close contact with the basement membrane. In
      perimakular areas many cells that have lost contact with the basement membrane,
      were localized deep in the epidermis. About 92 % of TRP1 positive perimakular
      cells were also vimentin positive. Vimentin positive cells were numerous in
      perimakular areas but missing in the macula of depigmentation. Dense groups of
      cells immunopositive for transcription factor Snail, known as inductor of
      epithelial-mesenchymal transition, were localized in perimakular areas in close
      proximity to the macula depigmentation border. Such cells were extremely rare
      within the macula of depigmentation. There is reason to assume that an intensive
      process, which is similar to the epithelial-mesenchymal transition, might be the
      cause of melanocyte death in perimakular field, and thus prevents repigmentation
      of depigmented areas.

PMID- 30188100
TI  - ITLN1, PPARg AND TNFa GENE EXPRESSION IN VISCERAL ADIPOSE TISSUE.
AB  - The adipose tissue is considered today as an endocrine organ in which tissue
      specific regulation of gene expression plays a key role in the processes of
      development of obesity and comorbidities, such as diabetes and cardiovascular
      disease. The present study is focused on ITLN1, PPARa and TNFa gene expression in
      intra-abdominal adipose tissue and its effect on the serum levels of omentin 1
      and TNFa in individuals with different body mass. It has been shown that serum
      TNFa level is significantly higher in the subgroup of patients with overweight
      and obesity (BMI >= 25 kg/m2) as compared to individuals with normal body weight
      (BMI < 25 kg/m2)( p < 0.03). We have demonstrated that the expression level of
      the PPARa gene is positively correlated with the ITLN1 gene expression level in
      the intra-abdominal adipose tissue (r = 0.516, p = 0.020). Serum level of omentin
      1 positively correlates with PPARa mRNA and protein levels in intra-abdominal
      adipose tissue (r = 0.550, p < 0.05 and r = 0.581, p < 0.03, respectively). For
      the subgroup of patients with overweight and obesity, we have shown negative
      correlation of the level of TNFa mRNA with PPARa and ITLN1 mRNA levels was shown
      (r = -0.549, p < 0.05 and r = -0.475, p < 0.05, respectively). This study is the
      first to show a correlation relationship between PPARa gene expression level in
      the intra-abdominal adipose tissue and the expression and secretion levels of
      omentin 1.

PMID- 30188101
TI  - REORGANIZATION OF INTERPHASE MICROTUBULES IN ROOT CELLS OF MEDICAGO SATIVA L.
      DURING ACCLIMATION TO OSMOTIC AND SALT STRESS CONDITION.
AB  - We have investigated the organization of microtubule system in interphase cells
      of Medicago sativa L. roots during acclimation to salt and osmotic stress at
      different concentrations of NaCl, Na2SO4 and mannitol. We have identified several
      morphological changes in tubulin cytoskeleton that appear during the acclimation
      to salt and osmotic stress in the cells of different root tissues: 1) decreased
      density of cortical microtubule network, 2) random orientation of cortical
      microtubule bundles, 3) non-uniform density of the bundles, 4) thickening of the
      bundles, 5) fragmentation of the bundles, 6) formation of centers of converging
      microtubule. Reduced density of the microtubule network and thickening of the
      bundles was detected during osmotic and salt stress, yet random orientation of
      cortical microtubules was observed under osmotic stress and not found during salt
      stress. Fragmentation of microtubule bundles was apparent during salt stress and
      less evident at high concentration of mannitol. Formation of centers of
      converging microtubule was common under prolonged action of sodium sulfate, less
      common under sodium chloride and not found after mannitol treatment. Our data
      show that cortical microtubules in alfalfa root cells rearrange not only in
      response to different ions, but also to osmotic pressure. Thus, the signaling
      pathways and molecular mechanisms inducing reorganization of the microtubule
      system may be triggered not only by sodium cations but also by sulfate and
      chloride anion at the concentrations that do not cause irreversible cell damage.
      Our study show that the osmotic and salt stress differently affect the cortical
      microtubules, and their reorganization in response to stress depends on the salt
      cations as well as anions might also show additional effect under salt stress.

PMID- 30188102
TI  - COMPARISON OF THE CYTOTOXIC EFFECTS OF ZEARALENON AND T-2 TOXIN ON THE HORSES AND
      OXEN GERM CELL IN VITRO BEFORE AND AFTER CRYOPRESERVATION.
AB  - The article presents the results of the studies of cytotoxic effect of
      zearalenone and T-2 toxin on sperm of horses and bulls during incubation and
      after thawing according to the technology of sperm obtaining and cryopreservation
      in Kharkov. We first have shown in vitro toxic effects of different
      concentrations of zearalenone and T-2 toxin (from 0.5 to 0.01 mM) on the membrane
      stability, as well as quantitative and qualitative indicators of semen in
      stallions and bulls before and after freezing and thawing. It has been found that
      the biological activity of the native sperm in 1 h after addition of 0.5 mM
      zearalenone is not changed, and after thawing is reduced by 19.4 %, or 0.69 ball
      (P < 0.01) compared to control without toxin. T-2 toxin at a concentration of 0.5
      mM reduced the activity of the native sperm after an hour of incubation by 0.59
      ball (P < 0.01) and decreased it after thawing decreased by 60.28 %, or 2.14 ball
      (P < 0.001). 1 h of incubation with zearalenone at concentration of 0.25 mM did
      not affect the activity of the native sperm, but the activity after freeze-thaw
      deteriorated by 12.2 %, or 0.41 ball (P < 0.05). T-2 toxin at a concentration of
      0.25 mM reduced activity of native sperm after 1 h exposure by 0.46 ball (P <
      0.05), and after thawing spermatozoa degrade it by 1.77 ball (P < 0.001) compared
      to control without toxins. In our study, the lowest concentration giving a
      significant decrease in sperm parameters was 0.01 mM. The negative impact of
      zearalenone in such a dose on the native sperm was absent, and sperm after
      thawing only slightly reduced activity and perezhivayemost by 0.09 points and
      0.27 hours, respectively. The simultaneous addition of zearalenone and T-2 toxin
      at the same dose of 0.01 mM resulted in a decrease in biological perezhivayemost
      and absolute indicator of native sperm perezhivayemost by 0.36 points and 0.64
      hours (P < 0.05), respectively.

PMID- 30188104
TI  - COMPARISON OF THE SHAPE OF RABBIT MESENCHYMAL STROMAL CELLS DURING FIVE PASSAGES
      AFTER PRODUCTION OF PRIMARY CULTURE.
AB  - Cultivation of cells under artificial conditions is one of the necessary
      procedures when working with stem cells. At this stage, the cells lose control by
      the macroorganism, becoming independent systems. Therefore, during the passaging
      of the cells, the probability of undesirable modifications is increased. At
      present, there is not enough data on the first indications about modification of
      the cultured cells and when they can appear. In the work, the rabbit medullary
      mesenchymal stromal cells (MSCs) were studied during 5 passages after producing
      primary culture. The area and the spreading coefficient of a cell were used to
      evaluate the cell state. The measurements were made 1 h and 1 day after cell
      reseeding by analyzing digital images of intact living cells. During this time
      interval, the absolute values of the cell area increased with the passage number,
      whereas the increment of the cell growth area did not depend on the passage
      number. It is possible to distinguish three groups of cells. Smaller cells (the
      1st group) prevail in cell population of the 1st passage. Next, their proportion
      is decreased and the proportion of larger cells is increased. Passaging of the
      cells does not influence their spreading coefficient.

PMID- 30188103
TI  - CHANGING OF SILICA VALVES OF DIATOM SYNEDRA ACUS subsp. RADIANS INFLUENCED BY
      PACLITAXEL.
AB  - Diatoms are unicellular microscopic eukaryotes able to form species-specific
      frustules with micro- and nanostructures of biogenic silica. The morphogenesis of
      frustules components occurs intracellularly within special organelles under
      control of cytoskeleton. The mechanisms of morphogenesis control are not clear.
      The influence of paclitaxel, the microtubule inhibitor, onto morphogenesis of
      valve of pennate diatom Synedra acus subsp. radians was investigated. It has been
      shown that microtubule disturbance on the early morphogenesis stages provoke
      symmetry axis displacement of immature valve followed by curvature of the valve.
      At subsequent stages of morphogenesis stages, disturbance of the fine silica
      micro- and submicroscale structures (areolae and velums) occurs. It is supposed
      that a necessary condition for successful diatom valve morphogenesis is a balance
      between stable and dynamic microtubules.

PMID- 30188105
TI  - ROLE OF INNATE LYMPHOID CELLS DURING CANCER.
AB  - It is well known that inflammatory infiltrates in many cases present in the tumor
      tissue. In addition, to date, convincing evidence for its predictive value for
      different types of cancer. To the cells of the adaptive immune system, until
      recently, received more attention but in the last decade has seen a growing
      number of publications on the participation of innate immunity in cancer
      processes. This interest is partly due to the fact that in a separate class of
      innate lymphoid cells were isolated relatively recently. However, when analyzing
      the literature becomes apparent lack of information about the significance of
      lymphocytes in vivo innate immunity in the tumor microenvironment formation,
      angiogenesis, tumor cells motility acquisition and invasive properties, but also
      for the prediction of the occurrence other forms of progression. This review
      attempts to structure the available data on the lymphoid cells of the innate
      immune system, give the brief descriptive characteristics of each subclass, light
      the question of plasticity of these cells and interaction with the adaptive
      immune system. Special attention is given to the analysis of the role of the ILC
      in reparative regeneration as physiological prototype of events that underlie in
      tumor progression.

PMID- 30188106
TI  - INFLUENCE OF HDAC INHIBITOR SODIUM BUTYRATE ON THE EXPRESSION OF DNA REPAIR GENES
      Rad51 AND XRCC5 IN mEras-Waf1+/+ AND mEras-Waf1-/-.
AB  - Mouse embryonal fibroblasts with knockout of CDKN1A gene encoding p21/Waf1
      protein transformed by oncogenes E1A and cHa-ras (mEras-Waf1-/- cell line) have
      been used to assess the level of DNA repair genes expression - Rad51 and XRCC5
      after treatment with HDAC inhibitor sodium butyrate as compared with their
      control counterparts (mEras-Waf1+/+ cells). mEras-Waf1-/- cells are characterized
      by the elevated amount of single-stranded DNA breaks and g-H2A.X histone foci
      associated with these breaks. According to immunofluorescence and immunobloting
      data, Rad51 and Ku80 proteins are highly expressed in the nuclei of both studied
      cell lines. The level of Ku80 is higher in cells with CDKN1A gene knockout. When
      cells were treated with DNA-damaging agent adriamycin, there was an additional
      accumulation of Rad51 foci in the nuclei. However, sodium butyrate reduced
      considerably the content of Rad51 and Ku80 proteins both in mEras-Waf1+/+ and
      mEras-Waf1-/- cells as well as in the cells treated by adriamycin. RT-PCR and
      immunobloting data show that inhibitory effect of sodium butyrate takes place at
      the level of Rad51 and XRCC5 gene transcription and the content of Rad51 and Ku80
      proteins. The observed suppressive effect of HDACI on DNA repair components
      explains in part the mechanisms of antiproliferative function of HDAC inhibitors.
      Surprisingly, sodium butyrate was shown to activate the pluripotent genes
      transcription in mEras-Waf1+/+ and mEras-Waf1-/- cells, as exemplified by
      upregulation of Oct-4, Sox-2, Klf4, implying that these pluripotent genes are
      under negative control at the level of chromatin structure.

PMID- 30188107
TI  - INFLUENCE OF INFLUENZA A VIRUS AND BACTERIAL LIPOPOLYSACCHARIDE ON PROLIFERATION
      AND GENE EXPRESSION OF CYTOKINES AND OTHER CELLULAR FACTORS IN CELLS OF
      ESTABLISHED ENDOTHELIAL CELL LINE ECV-304.
AB  - Change of state of endothelial cells occurs under the action of viral infection
      and bacterial lipopolysaccharide (LPS) that leads to cell dysfunction. Therefore,
      the aim of the current study was to investigate the effect of LPS from
      Escherichia coli and influenza A virus on proliferative activity of human
      endothelial cells (ECV-304) and gene expression of several cytokines and cellular
      factors: TNFa, TGFa, IFN-a, MMP-9, NF-eB, Rho A, eNOS and iNOS. It was found that
      ECV-304 cells once infected with very low infectious doses of influenza virus
      acquire the ability to long-term active proliferation (over 8 passages). Addition
      of LPS E. coli reduced the virus-stimulated cell proliferation. It was shown that
      influenza virus and LPS can affect on gene expression of cytokine and other
      cellular factors. When endothelial cells had been infected with influenza A virus
      in the presence of LPS, there was a significant increase in the expression of
      several genes and replacement of some genes expression on the expression of other
      genes. Expression of MMP-9 gene was inhibited in the case of separate exposure to
      the virus and LPS, but it was significantly increased during the first day under
      the adding of the virus and LPS together, as well as the activity of the IFN-a
      gene; gene of TNFa was active for only 1-3 days whereas genes expression of other
      factors (TGFa, eNOS, iNOS, NF-eB and Rho A) increased significantly at the 5th
      day as in the case of adding only LPS. Thus, the change of physiological state of
      endothelial cells occurs in the presence of influenza A virus and LPS and it can
      be caused during different time periods (as well as by varying degrees of virus
      infection of cells) by different cellular factors and possibly with involvement
      of different signaling pathways.

PMID- 30188108
TI  - RSH ANTIOXIDANTS INCREASE INTRACELLULAR ROS LEVEL AND PROLIFERATION OF SP2/0
      MYELOMA CELLS IN SERUM-FREE MEDIUM.
AB  - At present research we have demonstrated the link between introducing of low
      molecular weight RSH-antioxidants (N-acetylcysteine, glutathione) into serum-free
      medium composition, reactive oxygen species (ROS) generation and mouse myeloma
      SP2/0-SF cells proliferative activity. The presence of these compounds in the
      medium changed the pattern of ROS-activity in cells by concentration-dependent
      manner, and affected their proliferative characteristics. The optimal value of
      the proliferative activity was related to 0.2 mM for both thyols and not depended
      from the thyol-compound nature. Further increasing up from the found
      concentration optimum lead to growth inhibition with different expression for N
      acetylcysteine and glutathione.

PMID- 30188109
TI  - RECOVERY OF DIVISION PROCESS IN BACTERIAL CELLS AFTER INDUCTION OF SulA PROTEIN
      WHICH IS RESPONSIBLE FOR CYTOKINESIS ARREST DURING SOS-RESPONSE.
AB  - SOS-response is an important tool of bacteria intended to protect their genome
      and thereby allow them to survive under adverse conditions. Recently SOS-response
      is considered to enhance mutagenesis and thus help bacteria acquire antibiotic
      resistance. Due to high significance of this phenomena it seems to be important
      to investigate processes that allow bacteria to survive after SOS-response
      activation. In current work the recovery of division process of Escherichia coli
      cells after division arrest due to expression of SOS-response protein SulA was
      studied. Data indicate that cells are able to rapidly restore normal division;
      also nucleoid occlusion seems to be the main septum positioning mechanism during
      the process. In the course of recovery FtsZ forms helix-like structures, which
      then transformate into Z-rings.

PMID- 30188110
TI  - Silver Nanowire-Based Fluorescence Thermometer for a Single Cell.
AB  - A fluorescence thermometer based on silver nanowires (AgNWs) is realized by
      assembling Texas Red (TR)-marked thermal-sensitive DNA stem-loops (TR-DNA stem
      loop) on the surface of AgNWs. Temperature configures the structure of the TR-DNA
      stem-loop and resultantly adjusts the energy transfer between TR and the AgNWs,
      which could sensitively control the fluorescence intensity of the thermometer.
      The thermometer is sensitive to the temperature ranging from 30 to 40  degrees C
      with the sensitivity of 2.6%/ degrees C. Under the assistance of laser confocal
      microscopy, a temperature change within a single cell was observed by the
      monofilament AgNW-based thermometer.

PMID- 30188111
TI  - Synthesis without Solvents: The Cluster (Nanoparticle) Beam Route to Catalysts
      and Sensors.
AB  - It is hard to predict the future of science. For example, when C60 and its
      structure were identified from the mass spectra of gas phase carbon clusters, few
      could have predicted the era of carbon nanotechnology which the discovery
      introduced. The solubilization and functionalization of C60, the identification
      and then synthesis of carbon nanotubes, and the generation and physics of
      graphene have made a scale of impact on the international R&D (and to some extent
      industrial) landscape which could not have been foreseen. Technology emerged from
      a search for molecules of astrochemical interest in the interstellar gas. This
      little sketch provides the authors with the confidence to present here a status
      report on progress toward another radical future-the synthesis of nanoparticles
      (typically metals) on an industrial scale without solvents and consequently
      effluents, without salts and their sometimes accompanying toxicity, with minimal
      prospects for unwanted nanoparticle escape into the environment, with a high
      degree of precision in the control of the size, shape and composition of the
      nanoparticles produced and with applications from catalysts and sensors to
      photonics, electronics and theranostics. In fact, our story begins in exactly the
      same place as the origin of the nanocarbon era-the generation and mass selection
      of free atomic clusters in a vacuum chamber. The steps along the path so far
      include deposition of such beams of clusters onto surfaces in vacuum, elucidation
      of the key elements of the cluster-surface interaction, and demonstrations of the
      potential applications of deposited clusters. The principal present challenges,
      formidable but solvable, are the necessary scale-up of cluster beam deposition
      from the nanogram to the gram scale and beyond, and the processing and
      integration of the nanoclusters into appropriate functional architectures, such
      as powders for heterogeneous catalysis, i.e., the formulation engineering
      problem. The research which is addressing these challenges is illustrated in this
      Account by examples of cluster production (on the traditional nanogram scale),
      emphasizing self-selection of size, controlled generation of nonspherical shapes,
      and nonspherical binary nanoparticles; by the scale-up of cluster beam production
      by orders of magnitude with the magnetron sputtering, gas condensation cluster
      source, and especially the Matrix Assembly Cluster Source (MACS); and by
      promising demonstrations of deposited clusters in gas sensing and in
      heterogeneous catalysis (this on the gram scale) in relevant environments (both
      liquid and vapor phases). The impact on manufacturing engineering of the new
      paradigm described here is undoubtedly radical; the prospects for economic
      success are, as usual, full of uncertainties. Let the readers form their own
      judgements.

PMID- 30188112
TI  - Quercetin Inlaid Silk Fibroin/Hydroxyapatite Scaffold Promotes Enhanced
      Osteogenesis.
AB  - There is a significant rise in the bone grafts demand worldwide to treat bone
      defects owing to continuous increase in conditions such as injury, trauma,
      diseases, or infections. Therefore, development of three-dimensional scaffolds
      has evolved as a reliable technology to address the current limitations for bone
      tissue regeneration. Mimicking the natural bone, in this study, we have designed
      a silk fibroin/hydroxyapatite scaffold inlaid with a bioactive phytochemical
      (quercetin) at different concentrations for promoting osteogenesis, especially
      focusing on quercetin ability for enhancing bone health. Characterization of the
      quercetin/silk fibroin/hydroxyapatite (Qtn/SF/HAp) scaffolds showed an increased
      pore size and irregular porous microstructure with good mechanical strength. The
      Qtn (low-content)/SF/HAp scaffold was found to be an efficient cell carrier
      facilitating cellular growth, osteogenic differentiation, and proliferation as
      compared to SF/HAp and Qtn (high-content)/SF/HAp scaffolds. However, Qtn (high
      content)/SF/HAp was observed to inhibit cell proliferation without any effects on
      cell viability. In vitro and in vivo outcomes studied using bone marrow-derived
      mesenchymal stem cells (rBMSCs) confirm the cytocompatibility, osteogenic
      differentiation ability, and prominent upregulation of the bone-specific gene
      expressions for the rBMSCs-seeded Qtn/SF/HAp scaffolds. In particular, the
      implanted Qtn (low-content)/SF/HAp scaffolds at the bone defect site were found
      to be well-attached and amalgamated with the surrounding tissues with
      approximately 80% bone volume recovery at 6 weeks after surgery as compared with
      other groups. Based on the aforementioned observations highlighting the quercetin
      efficiency for bone regeneration, the as-synthesized Qtn (low-content)/SF/HAp
      scaffolds can be envisioned to provide a biomimetic bone-like microenvironment
      promoting rBMSCs differentiation into osteoblast, thus suggesting a potential
      alternative graft for high-performance regeneration of bone tissues.

PMID- 30188113
TI  - Cardiac Stem Cell Patch Integrated with Microengineered Blood Vessels Promotes
      Cardiomyocyte Proliferation and Neovascularization after Acute Myocardial
      Infarction.
AB  - Cardiac stem cell (CSC) therapy has shown preclinical and clinical evidence for
      ischemic heart repair but is limited by low cellular engraftment and survival
      after transplantation. Previous versions of the cardiac patch strategy improve
      stem cell engraftment and encourage repair of cardiac tissue. However, cardiac
      patches that can enhance cardiomyogenesis and angiogenesis at the injured site
      remain elusive. Therapies that target cardiomyocyte proliferation and new blood
      vessel formation hold great potential for the protection against acute myocardial
      infarction (MI). Here, we report a new strategy for creating a vascularized
      cardiac patch in a facile and modular fashion by leveraging microfluidic
      hydrodynamic focusing to construct the biomimetic microvessels (BMVs) that
      include human umbilical vein endothelial cells (HUVECs) lining the luminal
      surface and then encapsulating the BMVs in a fibrin gel spiked with human CSCs.
      We show that the endothelialized BMVs mimicked the natural architecture and
      function of capillaries and that the resultant vascularized cardiac patch (BMV
      CSC patch) exhibited equivalent release of paracrine factors compared to those of
      coculture of genuine human CSCs and HUVECs after 7 days of in vitro culture. In a
      rat model of acute MI, the BMV-CSC patch therapy induced profound mitotic
      activities of cardiomyocytes in the peri-infarct region 4 weeks post-treatment. A
      significant increase in myocardial capillary density was noted in the infarcted
      hearts that received BMV-CSC patch treatment compared to the infarcted hearts
      treated with conventional CSC patches. The striking therapeutic benefits and the
      fast and facile fabrication of the BMV-CSC patch make it promising for practical
      applications. Our findings suggest that the BMV-CSC patch strategy may open up
      new possibilities for the treatment of ischemic heart injury.

PMID- 30188114
TI  - Unexpectedly High Levels of Organic Compounds Released by Indoor Photocatalytic
      Paints.
AB  - Photocatalytic paints based on titanium dioxide (TiO2) nanoparticles represent a
      promising treatment technology for cleaning the air at our dwellings. A few
      studies have shown that instead of elimination of harmful indoor air pollutants
      the production of carbonyl compounds occurs from the photocatalytic paints.
      Herein, we report unexpectedly high concentrations of volatile organic compounds
      (VOCs) released upon irradiation of photocatalytic paints which are meant to
      clean the air at our dwellings. The concentrations of the VOCs were measured
      continuously and online by PTR-ToF-MS (Proton Transfer Reaction-Time of Flight
      Mass Spectrometry) connected to a well-established flow tube photoreactor. The
      PTR-ToF-MS analysis revealed the presence of 52 ions in the mass range between 20
      and 490 amu, among which 43 have been identified. In particular very high
      emission rates were estimated of two relevant indoor air pollutants, formaldehyde
      and acetaldehyde as 355 MUg h-1 and 257 MUg h-1 for 1 m2, respectively. We
      suggest a detailed reaction mechanism responsible for the production of these
      harmful indoor air pollutants (formaldehyde and acetaldehyde, among the others).
      The hydroxyl radicals (OH) formed upon activation of TiO2, react with the organic
      constituent (butyl acrylate and vinyl acetate) of the paint binder lead to
      generation of an important number of organic compounds. We demonstrate that the
      TiO2 quantity and the organic content of the binder is of paramount importance
      with respect to the formation of VOCs, which should be considered for future
      optimization of this air remediation technology based on TiO2 nanoparticles.

PMID- 30188115
TI  - Afterglow Resonance Energy Transfer Inhibition for Fibroblast Activation Protein
      alpha Assay.
AB  - Traditional photoluminescence resonance energy transfer (PRET)-based sensors are
      widely applied, but still suffer from the severe background interference from in
      situ excitation. The afterglow nature of the persistent luminescence
      nanoparticles (PLNPs) allows optosensing after the stoppage of in situ
      illumination, and thus subtly overcomes that interference. We proposed a simple
      strategy for functionalizing PLNPs for bioanalytical applications and the new
      afterglow resonance energy transfer (ARET)-based assay for quantitative
      determination and imaging of fibroblast activation protein-alpha (FAPalpha) in
      live cells using Au-decorated Cr3+0.004:ZnGa2O4 as donor and Cy5.5-KGPNQC-SH as
      acceptor. The ARET between the donor and acceptor quenches the afterglow of the
      donor, and the cleavage of peptide KGPNQC by FAPalpha inhibits the ARET and
      restores the afterglow of the donor. The ARET-based assay of FAPalpha, with the
      linear range of 0.1-2.0 mg.L-1 (1.2-22.9 nM), LOD of 11 MUg.L-1 (115 pM), and RSD
      of 3.9% (for 0.5 mg.L-1 FAPalpha, n = 5), displays higher sensitivity, lower
      limit of detection (LOD), and better anti-interference capability than the
      corresponding PRET-based assay. Besides, the ARET-based sensors are lighted up by
      the FAPalpha-positive U87MG and MDA-MB-435 cells, but kept in the dark when
      incubated in the FAPalpha-negative AD293 cells. The proposed ARET-based sensor
      can detect FAPalpha of U87MG and MDA-MB-435 living cells in human serum with the
      spiked recoveries of 95.6-103%. Our data demonstrated a simple and effective
      strategy for bridging PLNPs to bioanalytical applications, and an attractive ARET
      assay of FAPalpha.

PMID- 30188116
TI  - Deep UV Emission from Highly Ordered AlGaN/AlN Core-Shell Nanorods.
AB  - Three-dimensional core-shell nanostructures could resolve key problems existing
      in conventional planar deep UV light-emitting diode (LED) technology due to their
      high structural quality, high-quality nonpolar growth leading to a reduced
      quantum-confined Stark effect and their ability to improve light extraction.
      Currently, a major hurdle to their implementation in UV LEDs is the difficulty of
      growing such nanostructures from Al xGa1- xN materials with a bottom-up approach.
      In this paper, we report the successful fabrication of an AlN/Al xGa1- xN/AlN
      core-shell structure using an original hybrid top-down/bottom-up approach, thus
      representing a breakthrough in applying core-shell architecture to deep UV
      emission. Various AlN/Al xGa1- xN/AlN core-shell structures were grown on
      optimized AlN nanorod arrays. These were created using displacement Talbot
      lithography (DTL), a two-step dry-wet etching process, and optimized AlN metal
      organic vapor phase epitaxy regrowth conditions to achieve the facet recovery of
      straight and smooth AlN nonpolar facets, a necessary requirement for subsequent
      growth. Cathodoluminescence hyperspectral imaging of the emission characteristics
      revealed that 229 nm deep UV emission was achieved from the highly uniform array
      of core-shell AlN/Al xGa1- xN/AlN structures, which represents the shortest
      wavelength achieved so far with a core-shell architecture. This hybrid top
      down/bottom-up approach represents a major advance for the fabrication of deep UV
      LEDs based on core-shell nanostructures.

PMID- 30188118
TI  - Assembly of DNA-Templated Bioluminescent Modules for Amplified Detection of
      Protein Biomarkers.
AB  - By virtue of its self-illuminating mechanism, the bioluminescence resonance
      energy transfer (BRET) technique has recently emerged as a promising platform for
      point-of-care (POC) diagnostics. However, due to the difficulty of incorporating
      generic affinity elements, such as aptamers and antibodies, current BRET-based
      methods are still not applicable to most clinically important biomarkers.
      Furthermore, the inability of these methods to amplify BRET signals leads to
      limited sensitivity in some applications. Here, we present a modular strategy for
      amplified BRET detection of protein biomarkers in human peripheral blood samples.
      In this strategy, a DNA-templated bioluminescent module was constructed by
      simultaneously binding luciferase and green fluorescent protein to one DNA
      template in a site-specific manner. The proposed modules showed high energy
      transfer efficiency and could be assembled into long self-illuminating polymers.
      Owing to this modular design, aptamers and antibodies were rationally
      incorporated, enabling specific assembly of multiple bioluminescent modules on
      one target. This strategy realized amplified BRET assays for human alpha-thrombin
      and prostate specific antigen (PSA) with the detection limit in the picomolar
      range using either a spectrophotometer or a smartphone. The modularity of our
      strategy allowed detection of different biomarkers by simple exchange of affinity
      elements. Furthermore, the self-illumination and isothermal amplification
      performance of this strategy make it an attractive tool for POC diagnostics.

PMID- 30188119
TI  - Data-Driven Rescoring of Metabolite Annotations Significantly Improves
      Sensitivity.
AB  - When analyzing mass spectrometry imaging data sets, assigning a molecule to each
      of the thousands of generated images is a very complex task. Recent efforts have
      taken lessons from (tandem) mass spectrometry proteomics and applied them to
      imaging mass spectrometry metabolomics, with good results. Our goal is to go a
      step further in this direction and apply a well established, data-driven method
      to improve the results obtained from an annotation engine. By using a data-driven
      rescoring strategy, we are able to consistently improve the sensitivity of the
      annotation engine while maintaining control of statistics like estimated rate of
      false discoveries. All the code necessary to run a search and extract the
      additional features can be found at https://github.com/anasilviacs/sm-engine and
      to rescore the results from a search in https://github.com/anasilviacs/rescore
      metabolites .

PMID- 30188117
TI  - P-Glycoprotein-Targeted Photothermal Therapy of Drug-Resistant Cancer Cells Using
      Antibody-Conjugated Carbon Nanotubes.
AB  - P-Glycoprotein (Pgp)-medicated multidrug resistance (MDR) remains a formidable
      challenge to cancer therapy. As conventional approaches using small-molecule
      inhibitors failed in clinical development because of the lack of cancer
      specificity, we develop Pgp-targeted carbon nanotubes to achieve highly cancer
      specific therapy through combining antibody-based cancer targeting and
      locoregional tumor ablation with photothermal therapy. Through a dense coating
      with phospholipid-poly(ethylene glycol), we have engineered multiwalled carbon
      nanotubes (MWCNTs) which show minimum nonspecific cell interactions and maximum
      intercellular diffusion. After chemically modifying with an anti-Pgp antibody,
      these MWCNTs showed highly Pgp-specific cellular uptake. Treatment of the
      targeted MWCNTs caused dramatic cytotoxicity in MDR cancer cells upon
      photoirradiation, whereas they did not cause any toxicity in the dark or
      phototoxicity toward normal cells that do not express Pgp. Because of excellent
      intratumor diffusion and Pgp-specific cellular uptake, the targeted MWCNTs
      produced strong phototoxicity in tumor spheroids of MDR cancer cells, a 3-D tumor
      model for studying tumor penetration and therapy. In conclusion, we have
      developed highly Pgp-specific MWCNTs that may provide an effective therapy for
      MDR cancers where other approaches have failed.

PMID- 30188120
TI  - Cluster-Based Anionic Template Assisted in the Formation of 3D Cobalt Cationic
      Framework: A Bridge Connecting MOFs and Halometallates?
AB  - The marriage of metal-organic framework (MOF) and metal halide gives birth to a
      novel 3D cationic MOF, [Co(tib)2].[Cu4I6] (1, tib = 1,3,5-tris(1
      imidazolyl)benzene), templated by anionic iodocuprate cluster (CuI4I62-). 1
      features a (3,6)-connected network with CoII and tib moieties as six-connected
      and three-connected nodes, respectively. It is notable that the template
      (iodocuprate cluster) in 1 is distinct from the widely utilized species such as
      organic solvents, ionic liquids, organic amines, and surfactants. This
      Communication provides a new avenue to fabricate halometallate-directed MOF via
      incorporating halometallate into MOF. The photocatalytic activity toward the
      degradation of methyl orange in aqueous solution under visible-light irradiation
      has also been studied.

PMID- 30188121
TI  - Optimal Design of Sulfidated Nanoscale Zerovalent Iron for Enhanced
      Trichloroethene Degradation.
AB  - Sulfidated nanoscale zerovalent iron (S-nZVI) has the potential to be a cost
      effective remediation agent for a wide range of environmental pollutants,
      including chlorinated solvents. Various synthesis approaches have yielded S-nZVI
      consisting of a Fe0 (or Fe0/S0) core and FeS shell, which are significantly more
      reactive to trichloroethene (TCE) than nZVI. However, their reactivity is not as
      high as palladium-doped nZVI (Pd-nZVI). We synthesized S-nZVI by the co
      precipitation of FeS and Fe0 by using Na2S during the borohydride reduction of
      FeSO4 (S-nZVIco). This resulted in FeS structures bridging the nZVI core and the
      surface, as confirmed by electron microscopy and X-ray analyses. The TCE
      degradation capacity of up to 0.46 mol TCE/mol Fe0 was obtained for S-nZVIco at a
      high S loading and was comparable to Pd-nZVI but 60% higher than the currently
      most reactive S-nZVI, in which FeS only coats the nZVI (S-nZVIpost). The high TCE
      degradation was due to complete utilization of Fe0 (2 e-/mol Fe0) toward the
      formation of acetylene. Although Pd-nZVI yielded 3 e-/mol Fe0, TCE degradation
      was comparable because it reduced acetylene further to ethene and ethane. Under
      Fe0-limited conditions, the S-nZVIco TCE degradation rate was 16 times higher
      than that of Pd-nZVI (0.5 wt % Pd) and 90 times higher than that of S-nZVIpost.

PMID- 30188122
TI  - MicroRNA Detection through DNAzyme-Mediated Disintegration of Magnetic
      Nanoparticle Assemblies.
AB  - DNA-assembled nanoparticle superstructures offer numerous bioresponsive
      properties that can be utilized for point-of-care diagnostics. Functional DNA
      sequences such as deoxyribozymes (DNAzymes) provide novel bioresponsive
      strategies and further extend the application of DNA-assembled nanoparticle
      superstructures. In this work, we describe a microRNA detection biosensor that
      combines magnetic nanoparticle (MNP) assemblies with DNAzyme-assisted target
      recycling. The DNA scaffolds of the MNP assemblies contain substrate sequences
      for DNAzyme and can form cleavage catalytic structures in the presence of target
      DNA or RNA sequences, leading to rupture of the scaffolds and disintegration of
      the MNP assemblies. The target sequences are preserved during the cleavage
      reaction and release into the suspension to trigger the digestion of multiple DNA
      scaffolds. The high local concentration of substrate sequences in the MNP
      assemblies reduces the diffusion time for target recycling. The concentration of
      released MNPs, which is proportional to the concentration of the target, can be
      quantified by a 405 nm laser-based optomagnetic sensor. For the detection of let
      7b in 10% serum, after 1 h of isothermal reaction at 50  degrees C, we found a
      linear detection range between 10 pM and 100 nM with a limit of detection of 6
      pM. For the quantification of DNA target in buffer solution, a limit of detection
      of 1.5 pM was achieved. Compared to protein enzyme-based microRNA detection
      methods, the proposed DNAzyme-based biosensor has an increased stability, a
      reduced cost and a possibility to be used in living cells, all of which are
      valuable features for biosensing applications.

PMID- 30188123
TI  - Effects of Design Choices on the Stiffness of Wireframe DNA Origami Structures.
AB  - DNA origami is a powerful method for the creation of 3D nanoscale objects, and in
      the past few years, interest in wireframe origami designs has increased due to
      their potential for biomedical applications. In DNA wireframe designs, the
      construction material is double-stranded DNA, which has a persistence length of
      around 50 nm. In this work, we study the effect of various design choices on the
      stiffness versus final size of nanoscale wireframe rods, given the constraints on
      origami designs set by the DNA origami scaffold size. An initial theoretical
      analysis predicts two competing mechanisms limiting rod stiffness, whose
      balancing results in an optimal edge length. For small edge lengths, the bending
      of the rod's overall frame geometry is the dominant factor, while the flexibility
      of individual DNA edges has a greater contribution at larger edge lengths. We
      evaluate our design choices through simulations and experiments and find that the
      stiffness of the structures increases with the number of sides in the cross
      section polygon and that there are indications of an optimal member edge length.
      We also ascertain the effect of nicked DNA edges on the stiffness of the
      wireframe rods and demonstrate that ligation of the staple breakpoint nicks
      reduces the observed flexibility. Our simulations also indicate that the
      persistence length of wireframe DNA structures significantly decreases with
      increasing monovalent salt concentration.

PMID- 30188124
TI  - Positive and Negative Two-Dimensional Thermal Expansion via Relaxation of Node
      Distortions.
AB  - The ability to tune physical properties is attractive for the development of new
      materials for myriad applications. Understanding and controlling the structural
      dynamics in complicated network structures like coordination polymers (CPs) is
      particularly challenging. We report a series of two-dimensional CPs
      [Mn(salen)]2[M(CN)4]. xH2O (M = Pt (1), PtI2 (2), and MnN (3)) incorporating
      zigzag cyano-network layers that display composition-dependent anisotropic
      thermal expansion properties. Variable-temperature single-crystal X-ray
      structural analyses demonstrated that the thermal expansion behavior is caused by
      double structural distortions involving [Mn(salen)]+ units incorporated into the
      zigzag layers. Thermal relaxations produce structural transformations resulting
      in positive thermal expansion for 2.H2O and negative thermal expansion for 3. In
      the case of 1.H2O, the relaxation does not occur and zero thermal expansion
      results in the plane between 200 to 380 K. The present study proposes a new
      strategy based on structural distortions in coordination networks to control
      thermal responsivities of frameworks.

PMID- 30188125
TI  - Absolute Configurations and Bioactivities of Guaiane-Type Sesquiterpenoids
      Isolated from Pogostemon cablin.
AB  - Seven novel guaiane sesquiterpenoids (1-7) and three known seco-guaianes were
      isolated from the volatile oil of Pogostemon cablin. Their structures including
      absolute configurations were determined by spectroscopic analyses, a modified
      Mosher's method, and X-ray diffraction and ECD data. The results indicated that
      the ECD Cotton effects arising from one or two nonconjugated olefinic
      chromophores could be applied to define the absolute configurations of guaiane
      sesquiterpenoids. Compounds 3 and 6 exhibited significant vasorelaxant activity
      against phenylephrine-induced and KCl-induced contractions of rat aorta rings
      [half-maximal effective concentration (EC50) of 3 against PHE-induced
      contraction, 5.4 MUM; EC50 of 6 against PHE- and KCl-induced contractions, 1.6
      and 24.2 MUM, respectively]. They also showed antifungal activity against Candida
      albicans (minimum inhibitory concentrations, 500 and 300 MUM, respectively). In
      addition, 2 and 7-9 displayed a neuroprotective effect against glutamate-induced
      injury in PC12 cells.

PMID- 30188126
TI  - 1-(Phenylsulfonyl)-3-oxabicyclo[3.1.0]hexan-2-one as a Building Block in Organic
      Synthesis.
AB  - The transformation of the readily available phenylsulfonyl lactone building block
      to structurally diverse molecular scaffolds is described. Depicted structures are
      accessed in one to three steps, and their overall yields are high. The rigidity
      of the starting building block greatly directs the stereoselectivity of the
      transformations, and newly generated stereogenic centers including the quaternary
      carbon centers are formed with high stereoselectivity generally superior to dr >
      95:1.

PMID- 30188127
TI  - Revealing the Activity Distribution of a Single Nanocatalyst by Locating Single
      Nanobubbles with Super-Resolution Microscopy.
AB  - It is challenging to uncover the catalytic activity at different locations of a
      single nanocatalyst for gas-generating reactions in real time. This research uses
      super-resolution microscopy to localize the center of single nanobubbles and
      reveal the local activity distribution at several to tens of nanometers accuracy.
      The distances between the centers of the nanobubbles and the center of the
      nanoplate usually distribute in a certain range from 0 to 500 nm, with the
      maximum population exhibiting at ~200 nm. This research also shows that more
      nanobubbles appear near the tips of the Pd-Ag nanoplate compared with the edges,
      which indicates higher activity at the tips. In addition, the relationship
      between the location, lifetime, and turnover rate of the nanobubbles was also
      carefully studied. This work presents an effective, high-resolution method to
      localize the activity distribution of nanocatalysts during gas-generating
      reactions, such as photocatalytic water splitting, dehydrogenation, and electro
      oxidation.

PMID- 30188128
TI  - Carrier Density-Dependent Localized Surface Plasmon Resonance and Charge Transfer
      Observed by Controllable Semiconductor Content.
AB  - We discuss how the controllable carrier influences the localized surface plasmon
      resonance (LSPR) and charge transfer (CT) in the same system based on ultraviolet
      visible and surface-enhanced Raman scattering (SERS) measurements. The LSPR can
      be easily tuned from 580 to 743 nm by changing the sputtering power of Cu2S in
      the Ag and Cu2S composite substrate. During this process, surprisingly, we find
      that the LSPR is proportional to the sputtering power of Cu2S. This observation
      indicates that LSPR can be accurately adjusted by changing the content of the
      semiconductor, or even the carrier density. Moreover, we characterize the carrier
      density through the detection of the Hall effect to analyze the Raman shift
      caused by CT and obtain the relationships between them. These fundamental
      discussions provide a guideline for tunable LSPR and the investigation of CT.

PMID- 30188129
TI  - Isotope Effects in Water: Differences of Structure, Dynamics, Spectrum, and
      Proton Transport between Heavy and Light Water from ReaxFF Reactive Force Field
      Simulations.
AB  - Investigating properties of both heavy and light water at the atomistic level is
      essential to understanding chemical and biological processes in aqueous solution.
      However, appropriately describing their difference on the nanoscale is still
      challenging. Employing ReaxFF reactive molecular dynamics simulations, we
      systematically study the structure, dynamics, and spectra of heavy and light
      water. With the water force field potential we developed, the different features
      between heavy and light water can be simulated appropriately by the classical
      treatment on large size and time scale. Here, we also report the structural
      difference between D3O+ and H3O+ in bulk heavy/light water. In addition, the
      diffusion constants of heavy and light water are successfully reproduced, and the
      Grotthuss hopping mechanism of proton transport in liquid water is properly
      described as well. It allows us to study a complex system in heavy/light aqueous
      environments, such as proton transport, chemical reaction, and tracing the
      reaction mechanism with an isotope substitute.

PMID- 30188130
TI  - Imaging a Resonance-Dominant Polyatomic Reaction: F + CH3D -> CH3(nu2 = 2) +
      DF(nu).
AB  - The title reaction was studied in a crossed-beam scattering experiment at the
      collisional energy ( Ec) ranging from 0.46 to 4.53 kcal mol-1. Using a time
      sliced velocity-imaging technique, both the pair-correlated integral and
      differential cross sections were measured. On the basis of the observed
      structures in state-specific excitation functions and the patterns in the Ec
      evolution of product angular distributions, we inferred that the title reaction
      proceeds predominantly via a resonance-mediated pathway, in contrast to the
      previous findings in the isotopically analogous reactions where the alternative
      direct abstraction pathway often dominates the reactivity. Despite the complexity
      of numerous scattering resonances involved in this six-atom reaction, extending
      our understanding of the isolated resonance in the analogous benchmark F + HD
      (H2) reaction enables us to propose plausible mechanistic origins for the
      formation as well as the decay of the complicated overlapped resonances.

PMID- 30188131
TI  - Exploiting Complex Formation between Polysaccharides and Protein Microgels To
      Influence Particle Stabilization of W/W Emulsions.
AB  - Protein particles were complexed with polysaccharides, and the effect on their
      capacity to stabilize water-in-water (W/W) emulsions was investigated. Protein
      microgels were formed by heating aqueous solutions of whey protein isolate. The
      microgels were subsequently mixed with anionic or cationic polysaccharides: kappa
      carrageenan (kappa-car) or chitosan, respectively. The molar mass and radius of
      the complexes formed in dilute microgel suspensions (40 mg/L) were characterized
      by light scattering techniques as a function of the pH and the composition. The
      structure and stability of complexes formed at a higher microgel concentration (3
      g/L) were studied by confocal laser scanning microscopy. It was found that small
      stable complexes can be formed with kappa-car between pH 4.3 and pH 5.5 and with
      chitosan between pH 4.1 and pH 6.5, that is, both below and above the isoionic
      point of the microgels (pI = 5.0). Complexation with polysaccharides stabilized
      aqueous suspensions of microgels in the pH range where they flocculated in the
      absence of polysaccharides (4.3-5.5). W/W emulsions were produced by mixing
      dextran and poly(ethylene oxide) solutions. Microgels added to these emulsions
      spontaneously form a layer around the dispersed droplets, which inhibits
      coalescence to different extents depending on the conditions. The effect of
      complexation on the structure of the emulsions was investigated as a function of
      the pH. It is shown that stable liquid-like emulsions can be obtained in the pH
      range where emulsions containing only microgels flocculate.

PMID- 30188132
TI  - Enantioselective N-Heterocyclic Carbene-Catalyzed Kinetic Resolution of Anilides.
AB  - The N-heterocyclic carbene (NHC)-catalyzed enantioselective kinetic resolution of
      anilides (a kind of hemiaminals) is reported. Upon exposure to the reaction in
      the presence of an NHC precatalyst and base, catalytic C-O bond formation occurs,
      providing axially chiral isoindolinones in high yields with excellent
      enantioselectivities.

PMID- 30188133
TI  - Substitution-Controlled Selective Formation of Hexahydrobenz[ e]isoindoles and 3
      Benzazepines via In(OTf)3-Catalyzed Tandem Annulations.
AB  - A dramatic N-substituent controlled tandem annulation of 2-(2-(2
      bromoethyl)phenyl)-1-sulfonylaziridines with 1,3-dicarbonyl compounds has been
      developed. When the N-substituent was a 4-methylbenzenesulfonyl group (Ts),
      sequential ring opening of aziridines, nucleophilic substitution, and
      lactamization took place to provide a series of hexahydrobenz[ e]isoindole
      compounds in good yields with good diastereoselectivities. By contrast, 3
      benzazepine compounds were afforded in good yields via ring opening of aziridines
      and nucleophilic substitution when the N-substituent was the 4
      nitrobenzenesulfonyl group (Ns).

PMID- 30188135
TI  - Synthesis of 5 H-Dibenzo[ c, g]chromen-5-ones via FeCl3-Mediated Tandem C-O Bond
      Cleavage/6pi Electrocyclization/Oxidative Aromatization.
AB  - A novel and expedient method for transformation of readily available 1
      isochromanones bearing a diaryl allenic moiety at the C4-position to
      functionalized 5 H-dibenzo[ c, g]chromen-5-ones under mild conditions is
      developed. This strategy is based on the dual abilities of iron(III) chloride to
      promote selective C-O bond cleavage/6pi electrocyclization and an oxidative
      aromatization sequence.

PMID- 30188134
TI  - Effects of Ca2+ Ion Condensation on the Molecular Structure of Polystyrene
      Sulfonate at Air-Water Interfaces.
AB  - The structure of poly(sodium 4-styrenesulfonate) (NaPSS) polyelectrolytes at air
      water interfaces was investigated with tensiometry, ellipsometry, and vibrational
      sum-frequency generation (SFG) in the presence of low and high CaCl2
      concentrations. In addition, we have studied the foaming behavior of 20 mM NaPSS
      solutions to relate the PSS molecular structure at air-water interfaces to foam
      properties. PSS polyelectrolytes without additional salt exhibited significant
      surface activity, which can be tuned further by additions of CaCl2. The
      hydrophobicity of the backbone due to incomplete sulfonation during synthesis is
      one origin, whereas the effective charge of the polyelectrolyte chain is shown to
      play another major role. At low salt concentrations, we propose that the
      polyelectrolyte is forming a layered structure. The hydrophobic parts are likely
      to be located directly at the interface in loops, whereas the hydrophilic parts
      are at low concentrations stretched out into near-interface regions in tails.
      Increasing the Ca2+ concentration leads to ion condensation, a collapse of the
      tails, and likely to Ca2+ intra- and intermolecular bridges between
      polyelectrolytes at the interface. The increase in both surface excess and foam
      stability originates from changes in the polyelectrolyte's hydrophobicity due to
      Ca2+ condensation onto the PSS polyanions. Consequently, charge screening at the
      interface is enhanced and repulsive electrostatic interactions are reduced.
      Furthermore, SFG spectra of O-H stretching bands reveal a decrease in intensity
      of the low-frequency branch when c(Ca2+) is increased whereas the high-frequency
      branch of O-H stretching modes persists even for 1 M CaCl2. This originates from
      the remaining net charge of the PSS polyanions at the air-water interface that is
      not fully compensated by condensation of Ca2+ ions and leads to electric-field
      induced contributions to the SFG spectra of interfacial H2O. A charge reversal of
      the PSS net charge at the air-water interface is not observed and is consistent
      with bulk electrophoretic mobility measurements.

PMID- 30188136
TI  - Microfluidic Production of Poly(1,6-hexanediol diacrylate)-Based Polymer
      Microspheres and Bifunctional Microcapsules with Embedded TiO2 Nanoparticles.
AB  - Application of TiO2 as a photocatalyst and UV protector is restricted by the
      difficulties in the recovery of TiO2 nanoparticles after water treatment. In this
      work, TiO2 nanoparticles (Degussa P25) were immobilised within easily recoverable
      poly(1,6-hexanediol diacrylate) poly(HDDA)-based polymer microspheres produced by
      on-the-fly photopolymerization of microfluidically generated droplets. Because of
      fast polymerization reaction, TiO2 was uniformly distributed within the polymer
      network. The transformation of double bonds in terminal vinyl groups of HDDA
      monomer into single bonds during photopolymerization was confirmed by Fourier
      transform infrared spectroscopy. The microspheres containing 0.5 wt % TiO2
      embedded in a poly(HDDA) matrix degraded 80% of methylene blue from 1 ppm aqueous
      solution in 9 h under UV light irradiation of 0.9 mW/cm2 at 365 nm. The
      microspheres could easily be separated from water and used in repeated cycles
      without any loss in photocatalytic activity. The inclusion of TiO2 within a
      polymer matrix increased the thermal degradation temperature of the material from
      364 to 389  degrees C. Bifunctional microcapsules consisting of aqueous or liquid
      paraffin core enclosed within a TiO2/poly(HDDA) composite polymer shell were also
      prepared. The fluorescent dye calcein was encapsulated in the core with 100%
      efficiency.

PMID- 30188137
TI  - Asmic: An Exceptional Building Block for Isocyanide Alkylations.
AB  - Asmic addresses the long-standing challenge of alkylating isocyanides, providing
      access to isocyanides with diverse substitution patterns. The o-anisylsulfanyl
      group serves a critical dual role by facilitating deprotonation-alkylation and
      providing a latent nucleophilic site through an unusual arylsulfanyl-lithium
      exchange.

PMID- 30188138
TI  - In Situ Liquid Cell TEM Reveals Bridge-Induced Contact and Fusion of Au
      Nanocrystals in Aqueous Solution.
AB  - During nanoparticle coalescence in aqueous solution, dehydration and initial
      contact of particles are critically important but poorly understood processes. In
      this work, we used in situ liquid-cell transmission electron microscopy to
      directly visualize the coalescence process of Au nanocrystals. It is found that
      the Au atomic nanobridge forms between adjacent nanocrystals that are separated
      by a ~0.5 nm hydration layer. The nanobridge structure first induces initial
      contact of Au nanocrystals over their hydration layers and then surface diffusion
      and grain boundary migration to rearrange into a single nanocrystal. Classical
      density functional theory calculations and ab initio molecular dynamics
      simulations suggest that the formation of the nanobridge can be attributed to the
      accumulation of auric ions and a higher local supersaturation in the gap, which
      can promote dehydration, contact, and fusion of Au nanocrystals. The discovery of
      this multistep process advances our understanding of the nanoparticle coalescence
      mechanism in aqueous solutions.

PMID- 30188139
TI  - Multilayer Hydrogel Capsules of Interpenetrated Network for Encapsulation of
      Small Molecules.
AB  - We report on a facile capsule-based platform for efficient encapsulation of a
      broad spectrum of hydrophilic compounds with molecular weight less than 1000 g
      mol-1. The encapsulated compounds extend from low-molecular-weight anionic Alexa
      Fluor 532 dye and cationic anticancer drug doxorubicin (DOX) to fluorescein
      isothiocyanate-dextrans with Mw ranging from 4000 to 40 000 g mol-1. The pH
      sensitive hydrogel capsules with an interpenetrated network shell are synthesized
      by layer-by-layer assembly of poly(methacrylic acid) (PMAA, Mw = 150 000 g mol-1)
      and poly( N-vinylpyrrolidone) (PVPON, Mw = 1 300 000 g mol-1) on 5 MUm silica
      microparticles followed by chemical cross-linking of the PMAA multilayers.
      Following core dissolution, the result is a hollow microcapsule with PVPON
      interpenetrated in the PMAA network. The capsules exhibit a reversible change in
      the diameter with a swelling ratio of 1.5 upon pH variation from 7.5 to 5.5.
      Capsules cross-linked for 4 h display high permeability toward molecules with
      molecular weight under 1000 g mol-1 at pH = 7.5 but exclude dextran molecules
      with Mw >= 40 000 g mol-1. Encapsulation of small molecules was achieved at pH =
      7.5 followed by sealing the capsule wall with 40 000 g mol-1 dextran at pH = 5.5.
      This approach results in negatively charged molecules such as Alexa Fluor being
      entrapped within the capsule cavity, whereas positively charged molecules such as
      DOX are encapsulated within the negatively charged capsule shell. Considering the
      simple postloading approach, the ability to entrap both anionic and cationic
      small molecules, and the pH-responsiveness of the interpenetrated network in the
      physiologically relevant range, these capsules offer a versatile method for
      controlled delivery of multiple hydrophilic compounds.

PMID- 30188141
TI  - 10 Steps for Successful Full-Mouth Rehabilitation.

PMID- 30188140
TI  - Revelation on the Complex Nature of Mesoporous Hierarchical FAU-Y Zeolites.
AB  - The texture of mesoporous FAU-Y (FAUmes) prepared by surfactant-templating in
      basic media is a subject of debate. It is proposed that mesoporous FAU-Y consists
      of: (1) ordered mesoporous zeolite networks formed by a surfactant-assisted
      zeolite rearrangement process involving local dissolution and reconstruction of
      the crystalline framework, and (2) ordered mesoporous amorphous phases as Al-MCM
      41, which coexist with zeolite nanodomains obtained by a dissolution-reassembly
      process. By the present systematic study, performed with FAU-Y (Si/Al = 15) in
      the presence of octadecyltrimethylammonium bromide and 0 < NaOH/Si ratio < 0.25
      at 115  degrees C for 20 h, we demonstrate that mesoporous FAU zeolites consist,
      in fact, of a complex family of materials with textural features strongly
      impacted by the experimental conditions. Two main families have been disclosed:
      (1) for 0.0625 < NaOH/Si < 0.10, FAUmes are ordered mesoporous materials with
      zeolite walls, which coexist with zeolite nanodomains (100-200 nm) and (2) for
      0.125 < NaOH/Si < 0.25, FAUmes are ordered mesoporous materials with amorphous
      walls as Al-MCM-41, which coexist with zeolite nanodomains (5-100 nm). The
      zeolite nanodomains decrease in size with the increase of NaOH/Si ratio.
      Increasing NaOH/Si ratio leads to an increase of mesopore volume, while the total
      surface area remains constant, and to a decrease of strong acidity in line with
      the decrease of micropore volume. The ordered mesoporous materials with zeolite
      walls feature the highest acidity strength. The ordered mesoporous materials with
      amorphous walls present additional large pores (50-200 nm), which increase in
      size and amount with the increase of NaOH/Si ratio. This alkaline treatment of
      FAU-Y represents a way to obtain ordered mesoporous materials with zeolite walls
      with high mesopore volume for NaOH/Si = 0.10 and a new way to synthesize
      mesoporous Al-MCM-41 materials containing extralarge pores (50-200 nm) ideal for
      optimal diffusion (NaOH/Si = 0.25).

PMID- 30188142
TI  - Overcoming Anatomical Limitations: The New Frontier of Implantology.

PMID- 30188143
TI  - Oral Implantology: Myths Exposed in Recent Research.
AB  - Today, a variety of surgical and prosthetic protocols, implant designs, and
      prosthetic devices are used for implant dentistry, employing many different
      dental technologies. With a plethora of options available, choosing an implant
      system has become highly challenging for practitioners. Having an understanding
      of the role of different implant design properties may help clinicians make
      informed decisions. This article provides an overview of factors affecting
      osseointegration and preservation of bone and discusses the importance of
      surgical and prosthetic treatments that respect the biologic width and avoid
      interventions, such as cementation, that may disturb the surrounding soft and
      hard tissues.

PMID- 30188144
TI  - Changing Paradigms in Prosthetic Rehabilitation Following Maxillary and Midfacial
      Malignant Disease.

PMID- 30188145
TI  - Ultra-Wide-Diameter Implants Gaining Favor for Immediate Placement in Posterior
      Jaw.

PMID- 30188146
TI  - Use of Tuberosity Connective Tissue for Root Coverage and Ridge Augmentation:
      Background and Technique.
AB  - Excess tissue often exists distal to the upper second molar, creating a pocket in
      the maxillary tuberosity. When removed from this location, this tissue can serve
      as an optimal piece of connective tissue (CT), helping to both prevent
      periodontal disease and treat periodontal recession while also aiding in
      restorative dentistry. This tissue is an ideal CT for root coverage and soft
      tissue ridge-augmentation grafting. This article provides an overview of CT
      grafting, including a discussion of tuberosity CT and its advantages versus
      palatal CT. The authors describe two techniques for harvesting tuberosity tissue
      for CT grafts, the distal gingivectomy technique and the distal wedge technique,
      and show examples of various uses of tuberosity tissue for CT grafts.

PMID- 30188147
TI  - 10 Keys for Successful Esthetic-Zone Single Implants: Importance of Biotype
      Conversion for Lasting Success.
AB  - The concept of 10 keys for successful esthetic-zone single immediate implants is
      an evidenced-based summary for the treatment planning and replacement of a
      hopeless tooth in the maxillary anterior sextant. It includes two treatment
      planning, five surgical, and three prosthetic keys. These keys are aimed at
      minimizing soft- and hard-tissue complications to achieve an optimal long-term
      esthetic implant restoration. Based on the 10 keys, which were described in a
      prior publication and are reiterated herein, the management of an immediate
      implant in the esthetic zone is considered a complex SAC procedure (SAC =
      straightforward, advanced, and complex). The present article highlights the
      importance of connective tissue grafting as part of the 10 keys and its role in
      biotype conversion and esthetic success that endures.

PMID- 30188148
TI  - Treatment of Advanced Periodontal Disease: Keys to Achieving Restoration
      Longevity.
AB  - Dental treatment for periodontally compromised patients can be highly complicated
      and challenging. This article addresses the effectiveness of contemporary
      periodontal treatment modalities by depicting clinical cases of periodontal
      restoration and health that have been maintained for 20 or more years. The cases
      incorporate four key steps vital to achieving successful treatment of chronic
      adult periodontitis: debridement, occlusal stabilization, pocket elimination, and
      maintenance. These cases demonstrate proof of principle that if the treatment is
      carefully planned and executed precisely, the natural dentition can be maintained
      for long periods of time even in periodontally compromised patients.

PMID- 30188149
TI  - Use of Soft-Tissue and Bone Grafting to Treat Complex Recession With Root
      Prominence and Buccal Plate Deficiencies.
AB  - Beyond the traditional monotherapy of connective tissue grafting, the combination
      of orthodontic therapy, soft-tissue grafting, and bone grafting with biologics
      may provide ideal treatment for complex recession defects with root prominence,
      thin tissues, and buccal plate dehiscences. The authors propose the benefits of
      performing a preoperative evaluation of complex mucogingival defects with cone
      beam computed tomography (CBCT) technology and then considering surgical
      management with modalities like bone grafting and orthodontics in addition to the
      classic soft-tissue grafting approach. Regeneration of the complete periodontium
      may result in better long-term soft-tissue stability and tooth retention
      following treatment of complex recession cases.

PMID- 30188150
TI  - Papillary Retention Flap Design for Pocket Reduction/Regeneration: Case Series
      With Long-Term Follow-Up.
AB  - Many papillary preservation flap techniques exist for both resective and
      regenerative purposes. This article describes a papillary retention design based
      on palatal access showing a successful long-term outcome. The papilla
      preservation approach detailed here, which is a modification of Friedman's
      beveled flap for the palate, circumvents any manipulation of interproximal or
      buccal tissue, leaving papillary tissue untouched. Indications for this approach
      are very specific and its application is somewhat limited. However, the aim of
      the papillary retention flap as discussed is to eradicate pocket depths exceeding
      5 mm and possibly regenerate hard and connective tissue in these exclusive
      locations. This strategy may permit access to the labial portion of the
      interproximal root in particular cases.

PMID- 30188151
TI  - Restoration of Lost Interdental Papilla: A Surgical Technique.
AB  - Loss of interdental papilla due to trauma or inflammatory periodontal diseases
      presents significant esthetic-zone challenges to clinicians. Miniscule working
      spaces and limited blood supply to these areas render conventional surgical
      techniques somewhat unpredictable. The implementation of vertical releasing
      incisions can further jeopardize blood supply and leave unattractive scarring
      upon healing. This article discusses a surgical technique utilizing microscopes
      and microsurgical instruments to more effectively achieve esthetic results.
      Additionally, the article provides a brief overview on the development of
      periodontal plastic and reconstruction surgery and updated information to support
      previously published reports by this author.

PMID- 30188152
TI  - Miller Classification of Marginal Tissue Recession Revisited After 35 Years.
AB  - Published more than three decades ago, the original classification of marginal
      tissue recession described four classes of recession. For example, in Miller
      Class III recession, there were different scenarios in which complete root
      coverage could not be achieved. Today, however, newer surgical techniques have
      made it possible for clinicians to potentially achieve complete root coverage
      when interdental bone loss exists. Currently, dentistry has a better
      understanding of the role of interdental papilla. Therefore, this article
      presents a new classification of papilla form that emphasizes the significance of
      the width and height of the papilla. Additionally, an updated classification of
      periodontal terminology will be presented.

PMID- 30188153
TI  - The Evolution of the Socket Graft: Technique Considerations.

PMID- 30188154
TI  - Is a snake scarier than a gun? The ontogenetic-phylogenetic dispute from a new
      perspective: The role of arousal.
AB  - Organisms have to be able to detect threats in order to activate their defensive
      mechanisms. Previous research has suggested that evolutionary old stimuli have an
      advantage during visual processing. Recent evidence indicates that negative
      emotional stimuli have a greater effect on the cognitive system regardless of
      evolutionary relevance. We suggest that the arousal level of the stimuli could
      account for these mixed results. We investigated how visual processing is
      influenced by evolutionary relevant and modern threatening emotional stimuli.
      Furthermore, we manipulated the level of arousal (medium, high) of the
      threatening cues. Participants performed an odd-one-out visual search task, in
      which the target was always a threatening picture. Our results showed that
      participants detected modern threatening targets faster than they did
      evolutionary relevant ones. However, the interaction with arousal revealed that
      this was only true at high-arousal level; there was no difference between
      evolutionary relevant and modern threatening targets when presented at medium
      arousal level. To our knowledge, to date this is one of the first studies to show
      the importance of the arousal level of stimuli. On the basis of our findings, we
      suggest that increasing arousal level only heightens visual search performance
      with modern threatening cues. (PsycINFO Database Record

PMID- 30188155
TI  - Israeli Ethiopian female adolescents' perspectives on alliances with social
      workers: Agency, power and performing identity.
AB  - This qualitative study explored the perspectives of at-risk Israeli female
      adolescents of Ethiopian origin (N = 15) regarding barriers to forming alliances
      with social workers. The study's rationale was based on the idea that an alliance
      enables clients to bring forth challenges and difficulties that are directly
      related to their well-being and, as such, is fundamental to the helping process.
      Four themes were identified as barriers to the forming of alliances with social
      workers: social workers' lack of availability; clients' perceived loss of
      independence in the process of receiving help; clients' sense of being forced to
      perform a different self ("passing"); and clients' difficulties in "opening up."
      Our discussion contextualizes these findings within a critical discourse that
      sees intervention in a sociopolitical context. Implications for practice are
      offered. (PsycINFO Database Record

PMID- 30188157
TI  - Measurement error and person-specific reliability in multilevel autoregressive
      modeling.
AB  - An increasing number of researchers in psychology are collecting intensive
      longitudinal data in order to study psychological processes on an intraindividual
      level. An increasingly popular way to analyze these data is autoregressive time
      series modeling; either by modeling the repeated measures for a single individual
      using classic n = 1 autoregressive models, or by using multilevel extensions of
      these models, with the dynamics for each individual modeled at Level 1 and
      interindividual differences in these dynamics modeled at Level 2. However, while
      it is widely accepted in psychology that psychological measurements usually
      contain a certain amount of measurement error, the issue of measurement error is
      largely neglected in applied psychological (autoregressive) time series modeling:
      The regular autoregressive model incorporates innovations, or "dynamic errors,"
      but not measurement error. In this article we discuss the concepts of reliability
      and measurement error in the context of dynamic (VAR(1)) models, and the
      consequences of disregarding measurement error variance in the data. For this
      purpose, we present a preliminary model that accounts for measurement error for
      constructs that are measured with a single indicator. We further discuss how this
      model could be used to investigate the between-person reliability of the
      measurements, as well as the (person-specific) within-person reliabilities and
      any individual differences in these reliabilities. We illustrate the consequences
      of assuming perfect reliability, the preliminary model, and reliabilities, using
      an empirical application in which we relate women's general positive affect to
      their positive affect concerning their romantic relationship. (PsycINFO Database
      Record

PMID- 30188156
TI  - Family support: A possible buffer against disruptive events for individuals with
      and without remitted depression.
AB  - The current study sought to test the role of family support as a buffer of life
      stress for depressive symptoms in a sample of young adults at low- and high-risk
      for depression based on a previous history of depression. Ninety-seven young
      adults, 54 with remitted depression and 43 without prior history of depression,
      completed reports of family relationships, disruptive life events, and depressive
      symptoms at baseline and every 2 months for 10 months. Results revealed
      significant interactions between family environment and life events predicting
      Beck Depressive Inventory (BDI) scores at baseline, such that individuals with
      better family support were buffered from risk associated with life stress, and
      this was true even after accounting for a previous history of depression.
      Longitudinal analyses utilizing the Patient Health Questionnaire-9 (PHQ-9) as a
      depressive symptom measure did not find significant associations with family
      environment, but did find that more stressful events at baseline were associated
      with increasing levels of symptoms over time. Exploratory analyses suggest that
      discrepant findings for baseline versus longitudinal analyses may be due to
      differences in symptom measurement and to associations between family environment
      and cognitive features of depression. These findings provide qualified support
      for the continued relevance of families as stress buffers in young adulthood
      across a spectrum of risk for depression. (PsycINFO Database Record (c) 2018 APA,
      all rights reserved).

PMID- 30188158
TI  - An electrophysiological investigation of attentional bias in a PTSD population.
AB  - OBJECTIVE: Evidence relying on probe detection tasks suggests that anxious
      individuals exhibit an enhanced selective attentional bias toward emotional or
      threating stimuli, characterized by attentional vigilance or avoidance of threat.
      METHOD: Amplitude of P100 and P300 event-related potentials and behavioral
      measures of target detection were assessed during presentation of a dot-probe
      task in 18 posttraumatic stress disorder patients and 18 healthy controls to
      elucidate the effects of attentional bias toward threatening facial expressions.
      RESULTS: Perceptual (P100) processing of threat-face pairs revealed no evidence
      of attentional bias in posttraumatic stress disorder (PTSD) patients. PTSD
      patients exhibited larger P100 and P300 amplitude to probes replacing neutral
      rather than angry faces, indicating an increased allocation of early perceptual
      and later strategic processing away from anger-related stimuli. CONCLUSION: The
      present study provided no support for facilitated engagement in this sample of
      patients. Possible interpretations of the results related to differential
      processing of target probes replacing angry-neutral face pairs are discussed.
      (PsycINFO Database Record

PMID- 30188159
TI  - Negative world views after trauma: Neurophysiological evidence for negative
      expectancies.
AB  - OBJECTIVE: Negative views of both the self and the world are commonly seen in
      individuals who have suffered psychological trauma. These negative cognitions are
      thought to be significant as they are likely to play a critical role in
      furthering, if not promoting, other symptoms and exacerbating the dysfunction
      sometimes seen after a traumatic event. This has led to the inclusion of
      "persistent negative beliefs and expectations about oneself or the world" in the
      DSM-5 (American Psychiatric Association, 2013). Although there is considerable
      self-report and behavioral evidence for negative biases after trauma, there is
      less concurrent neurophysiological data. This study used the N400, an event
      related potential sensitive to semantic expectancies, to assess negative
      expectations in a trauma sample. METHOD: In this study, 39 participants completed
      an N400 task in which they read ambiguous sentence stems that ended either with a
      positive final word (Things will turn out . . . fine) or a negative final word
      (Things will turn out . . . badly). The authors predicted that those trauma
      survivors with negative cognitions (as measured by the Posttraumatic Cognitions
      Inventory [PTCI]: Foa et al., 1999) would show N400 amplitudes indicating
      expectancies for negative endings. Augmenting the previous self-report data, this
      would provide evidence for negative expectancies that are fairly early and
      relatively automatic. RESULTS: N400 amplitudes to negative sentence endings were
      significantly related to negative views of the world as measured by the PTCI.
      CONCLUSIONS: This suggests that negative world views in trauma survivors have
      demonstrable neurophysiological correlates and impact on expectations in
      ambiguous situations. (PsycINFO Database Record

PMID- 30188160
TI  - Reframing marginalization and youth development: Introduction to the special
      issue.
AB  - The field of developmental science was revolutionized, in part, by the
      publication of Garcia Coll and colleagues' (1996) integrative model for the study
      of developmental competencies in minority children. Nevertheless, much work
      remains as changes within and beyond academia will require greater innovation in
      the way marginalization is conceptualized and studied. In this introduction to
      the Special Issue, "New Directions in Developmental Science with Youth
      Experiencing Marginalization," we situate the contribution of the integrative
      model within a sociohistorical context and discuss how recent changes push us to
      reconsider the models and theories that guide existing work with youth who
      experience marginalization. We also introduce a nuanced definition of the term
      marginalization for the field to consider in relation to research on youth
      development. We define marginalization as a multidimensional, dynamic, context
      dependent, and diverse web of processes, rooted in power imbalance and
      systematically directed toward specific groups and individuals, with
      probabilistic implications for development. In the context of this discussion, we
      also highlight the important insights gleaned from the collection of articles
      included in this Special Issue and how they advance the field. (PsycINFO Database
      Record

PMID- 30188161
TI  - Contributions of the integrative model for the study of developmental
      competencies in minority children: What have we learned about adaptive culture?
AB  - The integrative model for the study of developmental competencies in minority
      children (Garcia Coll et al., 1996) is considered by many to have signaled a
      landmark shift in conceptualizing the normative development of minority children.
      Since its publication, the model has been widely used in child development
      scholarship to challenge deficit perspectives of ethnic-racial minority children
      and families, which were-and arguably still are-pervasive. In this article, we
      provide a systematic qualitative review of the research pertaining to what Garcia
      Coll and colleagues (1996) termed adaptive culture, which refers to "a social
      system defined by sets of goals, values, and attitudes that differs from the
      dominant culture" (p. 1896), and which on its own has been discussed in 93
      studies. We conclude with a critical discussion of areas of inquiry informed by
      the integrative model and recommendations for future directions in theory and
      empirical work. (PsycINFO Database Record

PMID- 30188162
TI  - Theorizing the benefits and costs of adaptive cultures for development.
AB  - Child socialization and development are, in part, products of adapting cultural
      systems. These systems evolve from the combined influence of collective history
      and current environmental affordances. They permeate family systems, shaping
      child development via numerous mechanisms, including structures and roles;
      values, beliefs, and goals; and parenting-to name a few. Recent growth in the
      study of child development among racial, ethnic, and cultural minority groups,
      which has been supported by important cultural-developmental theoretical
      advances, sheds essential light on the ways in which adapting cultural systems
      permeate child socialization and development in all families. Across this
      scholarship, there are numerous examples of the effectiveness of adapting
      cultural systems for promoting developmental competencies. There are also
      examples, however, in which adapting cultural systems either fail to promote
      developmental competencies or undermine the development of competencies. To
      address these theoretical and empirical tensions, we advance a set of
      propositions. Together, the propositions situate the developmental consequences
      of adapting cultural systems within multiple scientific traditions, including
      psychological, ecological, family systems, developmental, and biological
      perspectives. These propositions can support scientific inquiries aimed at
      identifying both the benefits and costs of adaptive cultures for development
      among diverse groups. (PsycINFO Database Record

PMID- 30188163
TI  - The development of purpose in life among adolescents who experience
      marginalization: Potential opportunities and obstacles.
AB  - In recent decades there has been a dramatic increase in the amount of research
      focused on purpose in life, demonstrating a host of benefits that emerge for
      individuals committed to a purpose. As with other constructs in the positive
      youth development framework, there is a paucity of work investigating how
      experiences of marginalization impact the development of this psychological asset
      among adolescents. To catalyze research on this front, we draw attention to
      potential opportunities and obstacles associated with experiences of
      marginalization and how they might affect an adolescent developing a purpose in
      life. Like Garcia Coll and colleagues' (1996) integrative model, our perspective
      includes sociocultural factors (e.g., social position, adaptive culture), an
      emphasis on intragroup variability, and discussion of potentially promoting and
      inhibiting aspects of marginalization. Following a description of existing
      research on purpose development during adolescence, we discuss how experiences of
      marginalization could contour the development of self-integrative, strong, and
      articulated purpose among adolescents. To conclude, specific considerations for
      future research are outlined, including how existing definitions of and tools for
      measuring purpose can be adapted to produce a scientific literature that values
      and includes the normative purpose development of adolescents who experience
      marginalization. (PsycINFO Database Record

PMID- 30188164
TI  - Understanding development of African American boys and young men: Moving from
      risks to positive youth development.
AB  - African American boys and young men in the United States face challenges unique
      to being a male and an ethnic minority in our society. Despite the
      marginalization of African American boys and young men, this article argues that
      African American boys and young men, like other individuals, are in large
      proportion able to overcome adversity and utilize positive youth development
      assets and resources, and that focusing on capabilities and strengths is worthy
      of primary emphasis (Lerner, Dowling, & Anderson, 2003; Stevenson, 2016). Garcia
      Coll and colleagues' (1996) integrative model of developmental competencies in
      minority children lays the groundwork for conceptualizing the profound influence
      of racism, economic disadvantage, oppression, segregation, and other trauma
      inducing experiences on the development of African American boys and young men.
      We extend that framework by adding notions of positive development and adaptive
      calibration to contextual challenges to account for prosocial development of
      African American boys and young men. We present descriptive and experimental
      research support for this approach and argue that it has the potential for
      increasing the validity, sophistication, and utility of developmental research on
      about African American boys and young men are presented. (PsycINFO Database
      Record

PMID- 30188165
TI  - New directions for racial discrimination research as inspired by the integrative
      model.
AB  - In 1996, Cynthia Garcia Coll and colleagues introduced a groundbreaking model
      that articulated factors that influenced the development of ethnic-racial
      minority and immigrant youth. One of the key arguments was that racial
      discrimination is a stratification mechanism resulting in negative developmental
      outcomes for minority youth, and this argument has been supported by several meta
      analyses. Against the backdrop of the rise of White nationalism, increasing hate
      crimes against ethnic-racial minority individuals, implementation of national
      policies that disproportionately affect communities of color, and the shift to a
      majority-minority country, it is imperative for future research to refine key
      aspects of the integrative model that are intricately connected to these trends.
      The present article offers recommendations for future research in 4 areas: (1)
      expansion of segregation indicators to include mass incarceration and mass
      deportation, (2) expansion of the study of resilience factors among minority
      youth, (3) application of the integrative model to White youth, and (4) the
      development of comprehensive measures and utilization of diverse methodologies.
      It is imperative that future research clarify these issues to further
      understanding of the development of all children in the context of racial
      discrimination. (PsycINFO Database Record

PMID- 30188166
TI  - An integrative risk and resilience model for understanding the adaptation of
      immigrant-origin children and youth.
AB  - We propose an integrative model for the adaptation of immigrant-origin children
      and youth that combines ecological with risk and resilience frameworks. Immigrant
      origin children and youth are now, and will continue to be, a diverse and
      demographically important segment of all postindustrial nations' populations.
      Synthesizing evidence across psychological, educational, and sociological
      disciplines produced since the seminal publication of Garcia Coll et al.'s (1996)
      model, along with significant events such as a global refugee crisis, a
      sociopolitical "deportation nation" climate, and heightened xenophobia, we
      provide a model for understanding the current conditions immigrant-origin
      children and youth encounter as they develop. This new integrative conceptual
      model for addressing positive frameworks for adaptation provides a culturally
      relevant approach for understanding both the risks and resilience of this
      population. The model was designed to inform practice and future research in the
      service of immigrant-origin children and youth. (PsycINFO Database Record

PMID- 30188167
TI  - Using attachment and relational perspectives to understand adaptation and
      resilience among immigrant and refugee youth.
AB  - Migration is a critical issue for child development in the 21st century. We
      expand on Garcia Coll et al.'s (1996) integrative model of minority child
      development by drawing from principles of attachment theory and interpersonal
      relationships research to offer new insights into how youth manage and respond to
      migration experiences. Immigrant and refugee youth should experience better
      outcomes to the extent that they (a) maintain strong relationships with
      caregivers and peers who provide a sense of closeness, safety, and confidence
      during the process of adjusting to this life transition and (b) find ways to
      establish a sense of connection and belonging to the new people, places,
      communities, and social networks within which they now live. Strong bonds to
      people and connection to places (both familiar and new) can counter the social
      stratification consequences to minority youth development that are well
      articulated in Garcia Coll et al.'s integrative model. The need for new and
      better strategies that promote the positive development of immigrant and refugee
      youth within their families, schools, workplaces, and communities is crucial, not
      only for individuals and families but for society as a whole. (PsycINFO Database
      Record

PMID- 30188169
TI  - Moral meta-narratives, marginalization, and youth development.
AB  - Morality, a central dimension of culture, is crucial for research on the
      development of youth experiencing marginalization. In this article, we discuss
      two main meta-narratives as moral frameworks that provide different meaning to
      the past and to cultural change: liberal progress, focused on the struggle of
      those who have historically experienced marginalization (e.g., racial/ethnic
      minorities), and community lost, focused on those who are experiencing some forms
      of marginalization in response to cultural and economic changes (e.g., rural
      Whites). Because these two meta-narratives represent a false dichotomy, we use
      relational epistemology principles-holism, identity of opposites, opposites of
      identity, and synthesis of wholes-to formulate an integrated metanarrative,
      community progress, to overcome this polarity and promote research on the
      development of all youth experiencing marginalization. Acknowledging and
      understanding these moral meta-narratives is crucial because they influence
      scientific discourse, political action, and policy that impacts marginalization
      and youth development. (PsycINFO Database Record

PMID- 30188168
TI  - Invisibility of racial/ethnic minorities in developmental science: Implications
      for research and institutional practices.
AB  - Garcia Coll et al.'s (1996) integrative model was a landmark article for
      developmental science, and for psychology more broadly, in outlining the
      multitude of social and cultural factors at play when seeking to understand the
      development of racial/ethnic minority children. The time is ripe to not only take
      stock of those advances but also evaluate the integrative model in the context of
      present-day research practice within developmental psychology, and psychology
      more broadly. The purpose of this article is to bring a systemic perspective to
      developmental science through a discussion of current practices in the field. To
      do so, we examine invisibility, or how dominant practices serve to overlook,
      silence, or dismiss knowledge produced by and for racial/ethnic minority
      populations. Guided by the interpretive framework of intersectionality (Crenshaw,
      1991), we discuss three key questions: From whose vantage point is research
      conducted? What types of questions are valued? And who gets left out? We then
      conclude with recommendations for changes in practices for individuals,
      institutions, and the field at large. Importantly, although our analysis is
      largely grounded in research and practices in developmental psychology, it is
      also highly relevant to psychological science as a whole. (PsycINFO Database
      Record

PMID- 30188170
TI  - Childhood family adversity and adult cortisol response: The role of observed
      marital conflict behavior.
AB  - Childhood family adversity predicts adult interpersonal behavior and
      physiological responses to interpersonal stress. Additionally, negative marital
      behaviors (e.g., hostility and distress maintaining attributions) predict
      maladaptive stress responses and mental health problems, whereas positive marital
      behaviors (e.g., acceptance and relationship enhancing attributions) predict
      adaptive physiological and psychological outcomes. The present study examined
      potential marital behavior mediators and moderators of the link between childhood
      adversity and cortisol responses to conflict. In a sample of 218 different-sex
      newlywed couples, we examined (a) actors' marital conflict behaviors as candidate
      mediators of the link between childhood adversity and cortisol responses to
      marital conflict discussions, and (b) partners' marital conflict behaviors as
      candidate moderators of the relation between childhood adversity and cortisol
      responses to marital discussions. Path analysis using actor-partner
      interdependence modeling did not confirm mediation. Instead, wives' childhood
      family adversity directly predicted husbands' attenuated cortisol responses, and
      wives' negative behavior predicted wives' attenuated cortisol responses. As
      hypothesized, wives' negative behaviors moderated the association between
      husbands' childhood family adversity and husbands' cortisol in response to
      conflict; husbands showed higher cortisol if they had experienced greater family
      adversity and if their wives displayed more negative behavior. Results suggest
      that childhood family adversity may carry forward to shape adult cortisol
      responses to conflict and highlights the importance of wives' negative behavior
      for both husbands and wives. These findings add to the family psychology
      literature by further clarifying how the interaction of stressful childhood
      experiences and conflict behaviors in marriage are associated with adult
      physiological responses to conflict. (PsycINFO Database Record

PMID- 30188172
TI  - Procedure Preference and "Intention-to-Treat" Outcomes after Listing for Lung
      Transplantation among U.S. Adults: A Cohort Study.
AB  - RATIONALE: Bilateral lung transplantation is widely used to treat chronic
      obstructive pulmonary disease (COPD) and interstitial lung disease (ILD), based
      on an expectation of improved survival after transplantation. Yet, waiting list
      mortality is higher while awaiting bilateral transplantation. The net effect of
      procedure preference on overall survival is unknown. OBJECTIVE: To determine
      whether an unrestricted procedure preference is associated with improved overall
      outcomes after listing for lung transplantation. METHODS: We performed a
      retrospective cohort study of 12,155 adults with COPD or ILD listed for lung
      transplantation in the U.S. between May 4, 2005 and December 31, 2014. We defined
      a "restricted" procedure preference as listing for "bilateral transplantation
      only" and an "unrestricted" procedure preference as listing for any combination
      of bilateral or single lung transplantation. We used a composite "intention-to
      treat" primary outcome that included events both before and after
      transplantation, defined as the number of days between listing and death, removal
      from the list for clinical deterioration, or re-transplantation. RESULTS: In
      adjusted analyses, an unrestricted procedure preference was associated with a 6%
      lower rate of the primary "intention-to-treat" outcome in COPD (adjusted hazard
      ratio (aHR) 0.94, 95% CI 0.86 to 1.03) and a 1% higher rate in ILD (aHR 1.01, 95%
      CI 0.94 to 1.07). There was no convincing evidence that these associations varied
      by age, disease severity, or the use of mechanical support. Among those with ILD
      and concomitant severe pulmonary hypertension, an unrestricted preference was
      associated with a 17% increased rate of the primary outcome (aHR 1.17, 95% CI
      0.99 to 1.39). An unrestricted preference was consistently associated with lower
      rates of death or removal from the list for clinical deterioration and with
      higher rates of transplantation. Graft failure was similar among those listed
      with restricted and unrestricted preferences. CONCLUSION: When considering
      outcomes both before and after transplantation, we found no evidence that COPD or
      ILD patients benefit from listing for bilateral lung transplantation compared to
      listing with a more liberal procedure preference. An unrestricted listing
      strategy for suitable candidates may increase the number of transplants performed
      without impacting overall survival.

PMID- 30188173
TI  - Corticosteroid Use and Incident Myocardial Infarction in Adults Hospitalized for
      Community-Acquired Pneumonia.
AB  - RATIONALE: Previous reports demonstrated that patients hospitalized for community
      acquired pneumonia (CAP) present an increased risk of myocardial infarction (MI).
      Corticosteroid treatment lowers CAP morbidity and mortality, but it is not known
      if it affects in-hospital MI. OBJECTIVES: The aim of the study was to investigate
      the potential interplay between corticosteroids treatment and in-hospital MI in
      CAP patients Methods: We retrospectively analyzed patients with CAP referred to
      the University-Hospital Policlinico Umberto I (Rome, Italy), consecutively
      recruited and prospectively followed-up until discharge. The primary outcome of
      this study was the occurrence of MI during hospitalization. Seven-hundred fifty
      eight patients (493 males, 265 females; age: 71.7 +/- 14.4 years) were included
      in the study: 241 (32%) were treated with systemic corticosteroids
      (methylprednisolone, betamethasone or prednisone) during in-hospital follow-up,
      whereas 517 patients were not treated with systemic corticosteroids. RESULTS:
      During the follow-up, 62 patients (8.2%) (0.72 per 100 person/days, 95% CI: 0.55
      to 0.92) had a MI. Patients treated with corticosteroids presented a lower
      incidence of MI compared to untreated ones (-0.48 per 100 person/days, 95%CI: 
      0.85 to -0.10). A Cox regression analysis showed that age, previous coronary
      heart disease and PaO2<60mmHg were positively associated to MI incidence, whereas
      corticosteroid therapy was negatively associated. Compared to patients not
      receiving corticosteroids, the propensity score-adjusted analysis confirmed that
      patients taking corticosteroids had a lower incidence of MI (HR: 0.461; 95% CI:
      0.243 - 0.876, p=0.018). CONCLUSIONS: This study shows that in-hospital
      corticosteroid treatment is associated with a lower incidence of MI within
      hospital-stay in CAP patients.

PMID- 30188171
TI  - A randomized clinical trial of interventions for improving well-being in
      custodial grandfamilies.
AB  - Despite the rising cultural phenomenon of grandparents parenting grandchildren on
      a full-time basis due to problems within the birth parent generation,
      intervention studies with these families have been scarce, methodologically
      flawed, and without conceptual underpinnings. We conducted a randomized clinical
      trial (RCT) with 343 custodial grandmothers recruited from across 4 states to
      compare the effectiveness of behavioral parent training (BPT), cognitive
      behavioral therapy (CBT), and information-only control (IOC) conditions at
      lowering grandmothers' psychological distress, improving their parenting
      practices, and reducing the internalizing and externalizing difficulties of
      target grandchildren between ages 4 and 12. These outcomes were derived
      conceptually from the family stress model and modeled as latent constructs with
      multiple indicators. Each RCT condition was fully manualized and delivered across
      10 sessions within groups led jointly by trained professionals and peer
      facilitators in community settings. Multidomain second-order latent difference
      score models were performed on a full intent-to-treat basis to compare the 3 RCT
      conditions on changes in the above outcomes from baseline to postintervention and
      from baseline to 6 months postintervention. In general, while CBT and BPT
      interventions were both superior to IOC at both times of measurement on most
      outcomes, they differed little from each other. Effect sizes were generally in
      the moderate to large range and similar to those found in prior studies of BPT
      and CBT with traditional birth parents. We conclude from this research that
      evidence-based interventions focusing on appropriate skill development and
      behavioral change can yield positive outcomes within custodial grandfamilies.
      (PsycINFO Database Record

PMID- 30188174
TI  - Barriers to Achieving Optimal Success with Medical Cannabis: Opportunities for
      Quality Improvement.
AB  - This commentary describes the clinician experience of certifying patients for
      medical cannabis (MC) in a north suburban Chicago integrative family medicine
      practice. The physician and research assistant performed a comprehensive chart
      review of the first 166 MC patients certified in the practice. Based on this
      review, barriers and opportunities were elucidated to improve delivery of MC
      therapy in Illinois within the existing framework of regulation, licensing,
      certification, and distribution. The following factors have posed challenges for
      the Illinois Medical Cannabis Pilot Program. These factors are interrelated and
      include: (1) inadequate scientific knowledge regarding effectiveness, dosage,
      delivery mechanism, indications, and drug interactions in humans; (2) lack of
      educational standards for dispensary and medical staff training; (3) lack of
      communication and coordination of patient care; (4) complexity and inconsistent
      availability of dosing options; and (5) barriers to access for patients seeking
      this therapy.

PMID- 30188175
TI  - Optimizing the Composition of Irrigation Fluid to Reduce the Potency of
      Staphylococcus aureus alpha-Toxin: Potential Role in the Treatment of Septic
      Arthritis.
AB  - Objective Septic arthritis is commonly caused by Staphylococcus aureus and is a
      medical emergency requiring antibiotics and joint irrigation. The bacteria
      produce alpha-toxin causing rapid cartilage cell ( chondrocyte) death. Saline
      (0.9%NaCl) lavage is normally used to remove bacteria and toxins, however, its
      composition might be suboptimal to suppress the lethal effects of alpha-toxin. We
      utilized rabbit erythrocyte hemolysis as a sensitive, biologically relevant assay
      of alpha-toxin levels to determine if changes to osmolarity, temperature, pH, and
      divalent cation (Mg2+, Ca2+) concentration were protective. Design Erythrocytes
      were incubated in the various conditions and then exposed to alpha-toxin
      ("chronic" challenge) or incubated with alpha-toxin and then exposed to
      experimental conditions ("acute" challenge). Results Raising osmolarity from 300
      mOsm (0.9%NaCl) to 400, 600, or 900 mOsm (sucrose addition) when applied
      chronically, significantly reduced hemolysis linearly. As an acute challenge,
      osmotic protection was significant and similar over 400 to 900 mOsm. Reducing
      temperature chronically from 37 degrees C to 25 degrees C and 4 degrees C
      significantly reduced hemolysis, however, when applied as an acute challenge
      although significant, was less marked. Divalent cations (Mg2+, Ca2+ at 5mM)
      reduced hemolysis. Varying pH (6.5, 7.2, 8.0) applied chronically marginally
      reduced hemolysis. The optimized saline (0.9% NaCl; 900 mOsm with sucrose, 5 mM
      MgCl2 (37 degrees C)) rapidly and significantly reduced hemolysis compared with
      saline and Hank's buffered saline solution applied either chronically or acutely.
      Conclusions These results on the effect of S. aureus alpha-toxin on erythrocytes
      showed that optimizing saline could markedly reduce the potency of S. aureus
      alpha-toxin. Such modifications to saline could be of benefit during joint
      irrigation for septic arthritis.

PMID- 30188176
TI  - Comparison of a 12-Week Whole-Body Exergaming Program on Young Adults:
      Differentiation in Flexibility, Muscle Strength, Reaction Time, and Walking Speed
      Between Sexes.
AB  - This study aimed to investigate the effects of exergaming on flexibility, muscle
      strength, reaction time, and walking speed of adults within sex differences.
      Fifty-four individuals participated in a 12-week exergaming program. Three 30-min
      sessions were conducted each week. Baseline and post-intervention assessments
      were done using the sit-and-reach and bend-over tests for flexibility, hand-held
      dynamometer for muscle strength, auditory and visual reaction time machine for
      reaction time, and 5-meter walk test for walking speed. There were no significant
      changes in the sit-and-reach, bend-over test, and auditory-visual reaction time
      for either gender ( p > .05) with the intervention. Walking speed and muscle
      strength improved after exergaming in both sexes ( p < .05). The study showed
      that the video gaming intervention led to significant and equal improvements in
      muscle strength and walking speed for both sexes; however, it had no impact on
      flexibility and auditory-visual reaction time.

PMID- 30188177
TI  - Safety and efficacy of aerobic exercise commenced early after cardiac surgery: A
      systematic review and meta-analysis.
AB  - BACKGROUND: Aerobic exercise is a critical component of cardiac rehabilitation
      following cardiac surgery. Aerobic exercise is traditionally commenced 2-6 weeks
      following hospital discharge and most commonly includes stationary cycling or
      treadmill walking. The initiation of aerobic exercise within this early
      postoperative period not only introduces the benefits associated with aerobic
      activity sooner, but also ameliorates the negative effects of immobilization
      associated with the early postoperative period. METHODS: A systematic review
      identified all studies reporting safety and efficacy outcomes of aerobic exercise
      commenced within two weeks of cardiac surgery. A meta-analysis was performed
      comparing functional, aerobic and safety outcomes in patients receiving early
      postoperative aerobic exercise compared with usual postoperative care. RESULTS:
      Six-minute walk test distance at hospital discharge was 419 +/- 88 m in early
      aerobic exercise patients versus 341 +/- 81 m in those receiving usual care (mean
      difference 69.5 m, 95% confidence interval (CI) 39.2-99.7 m, p < 0.00001). Peak
      aerobic power was 18.6 +/- 3.8 ml.kg-1.min-1 in those receiving early exercise
      versus 15.0 +/- 2.1 ml.kg-1.min-1 in usual care (mean difference 3.20 ml.kg-1.min
      1, 95% CI 1.45-4.95, p = 0.0003). There was no significant difference in adverse
      events rates between the two groups (odds ratio 0.41, 95% CI 0.12-1.42, p =
      0.16). CONCLUSION: Aerobic exercise commenced early after cardiac surgery
      significantly improves functional and aerobic capacity following cardiac surgery.
      While adverse event rates did not differ significantly, patients included were
      very low risk. Further studies are required to adequately assess safety outcomes
      of aerobic exercise commenced early after cardiac surgery.

PMID- 30188178
TI  - Does the mode of delivery in routine cardiac rehabilitation have an association
      with cardiovascular risk factor outcomes?
AB  - AIMS: Cardiac rehabilitation is one of the most cost-effective interventions for
      patients with cardiovascular disease. Worldwide supervised group-based cardiac
      rehabilitation is the dominant mode of delivery followed by facilitated self
      managed (FSM), which is emerging as part of a cardiac rehabilitation menu. Modern
      research evidence, using trials and well-resourced interventions, suggests FSM is
      comparable to supervised rehabilitation in its outcomes for patients; however,
      this is yet to be established using routine clinical practice data. METHODS:
      Including 81,626 patients from routine clinical data in the National Audit of
      Cardiac Rehabilitation, this observational study investigated whether mode of
      delivery, supervised or FSM, was associated with similar cardiac rehabilitation
      outcomes. Hierarchical regression models included patient and service covariates
      such as age, gender, cardiac rehabilitation duration and programme staff type.
      RESULTS: The results showed 85% of the population received supervised cardiac
      rehabilitation. The FSM group were significantly older, female and predominantly
      in lower socioeconomic groups. The results showed that all patients on average
      benefit from cardiac rehabilitation, independently of mode of delivery, across
      all risk factors. Additional benefit of 13% and 11.4% increased likelihood of
      achieving the target state for physical activity and body mass index respectively
      when using FSM approaches. CONCLUSION: This is the first study to investigate
      traditional cardiovascular risk factors with cardiac rehabilitation mode of
      delivery using routine clinical data. Both modes of delivery were associated with
      comparable statistically significant positive outcomes. Despite having equivalent
      outcomes, FSM cardiac rehabilitation continues to be underutilised, with less
      than 20% of patients receiving this mode of delivery in the UK.

PMID- 30188179
TI  - Editorial: Physical fitness is a modifiable predictor of early cardiovascular
      death.

PMID- 30188180
TI  - Development of a Collaborative Algorithm for the Management of Type 2 Diabetes
      during Ramadan: An Anchor on Empowerment.
AB  - Empowerment plays significant roles in the complex management of type 2 diabetes.
      International guidelines have provided recommendations on management of Muslims
      who fast during Ramadan. However, there remains a lack of patient-centered
      epistemic tool to empower healthcare providers and patients in managing diabetes
      during Ramadan. This study discussed the development and evaluation of such tool.
      The collaborative algorithm was developed with reference to the nominal group
      technique by a board-certified clinical pharmacist and discussed with
      endocrinologists, nurses, and family physicians. The empowerment component of the
      algorithm was developed based on the Basic Psychological Needs Theory. The
      algorithm was evaluated through a randomized controlled trial. Glycated
      hemoglobin (HbA1c), fasting plasma glucose (FPG), and postprandial glucose (PPG)
      levels and safety profiles in terms of hypoglycemic events were assessed. The
      collaborative algorithm was developed with four components: screening, education,
      dose modification by healthcare provider, and dose adjustment by patient. A total
      of 62 individuals were recruited, with 30 and 32 randomized into the intervention
      and control groups, respectively. The mean age was 58.4 years, with majority
      being females (67.7%). There was a reduction in mean HbA1c from 7.9% +/- 0.9% to
      7.5% +/- 0.8% (P < 0.001) in the intervention group, while no significant
      difference was observed in the control group (P = 0.270). FPG (P < 0.001) and PPG
      (P = 0.002) also improved significantly in the intervention group. There were no
      major hypoglycemic events and minor hypoglycemia comparable between both groups
      (P = 0.465). The collaborative algorithm incorporated empowerment and promoted
      shared decision-making in diabetes management, hence promoting safe and effective
      fasting.

PMID- 30188182
TI  - Nebulized Normal Saline Solution for Treatment of Bronchial Asthma Exacerbations
      and Bronchiolitis: Not Standard of Care.
AB  - Nebulized normal saline is frequently prescribed for the treatment of
      bronchiolitis or bronchial asthma exacerbations. We aimed to reinforce guidelines
      care by educating providers on the futility of saline administration. Frequency
      and indications for nebulized normal saline prescription were documented from
      November 1, 2014, to April 1, 2015, and then again, after dissemination of
      educational material to providers, from November 1, 2016, to April 1, 2017. A
      total of 263 patients had bronchiolitis and 470 had asthma. Nebulized normal
      saline for bronchiolitis decreased significantly in the emergency department (ED)
      and inpatient settings ( P < .001 and P = .027, respectively). For asthma
      exacerbations, the use of nebulized normal saline decreased significantly in the
      inpatient setting ( P = .025), while in the ED, numbers were low at baseline and
      remained unchanged. Nebulized normal saline administration in the hospital
      setting results in continued use in the community, where this leads to
      unnecessary ED visits, where first-line therapy should have been administered.

PMID- 30188183
TI  - The Lived Experiences of Adolescents With Cancer: A Phenomenological Study.
AB  - This descriptive phenomenological study was conducted to explore the lived
      experiences of adolescents with cancer. Purposive sampling was used to recruit
      participants. In-depth, nonstructured interviews were conducted to collect data,
      and narratives were analyzed using Colaizzi's seven-step method. Data saturation
      was achieved after interviewing 16 participants. The study was divided into three
      main themes and 16 subthemes: suffering (caused by symptoms, therapy, cancer
      recurrence, the feeling of being trapped in hospital, the burden of food therapy,
      delayed education, the absence of peer relationships, and limited activities),
      emotional reactions (fear, worry, sadness, anger, and loneliness), and
      rebalancing (strong family relationships, optimistic thinking, and healthy
      lifestyles). While adolescents with cancer experience changes in lifestyle, and
      physical, psychological, and social burden, they also have positive life
      experiences. Building appropriate learning systems, improving communication
      skill, and providing appropriate food therapy may alleviate the psychological
      burden experienced by young patients.

PMID- 30188181
TI  - Engaging Coalitions in Community-Based Childhood Obesity Prevention
      Interventions: A Mixed Methods Assessment.
AB  - BACKGROUND: Childhood obesity prevention interventions have engaged coalitions in
      study design, implementation, and/or evaluation to improve research outcomes;
      yet, no systematic reviews have been conducted on this topic. This mixed methods
      review aims to characterize the processes and dynamics of coalition engagement in
      community-based childhood obesity prevention interventions. METHODS: Data
      Sources: Studies extracted from Ovid MEDLINE, PubMed, and Web of Science;
      complementary original survey and interview data among researchers of included
      studies. Eligible Studies: Multisetting community-based obesity prevention
      interventions in high-income countries targeting children 0-12 years with
      anthropometric, behavioral, or environmental/policy outcomes. The Community-Based
      Participatory Research (CBPR) Conceptual Model was used as an overarching
      framework. RESULTS: Thirteen studies met inclusion criteria. Elements of CBPR
      were evident across all studies with community engagement in problem
      identification (n = 7), design/planning (n = 11), implementation (n = 12),
      evaluation (n = 4), dissemination (n = 2), and sustainability (n = 10) phases.
      Five studies reported favorable intervention effects on anthropometric (n = 4),
      behavioral (n = 1), and/or policy (n = 1) outcomes; descriptive associations
      suggested that these studies tended to engage community members in a greater
      number of research phases. Researchers involved in 7 of 13 included studies
      completed a survey and interview. Respondents recalled the importance of group
      facilitation, leadership, and shared understanding to multisector coalition work.
      Perceived coalition impacts included community capacity building and intervention
      sustainability. CONCLUSIONS: This review contributes to a deeper understanding of
      intervention processes and dynamics within communities engaged in childhood
      obesity prevention. Future research should more rigorously assess and report on
      coalition involvement to assess the influence of coalitions on multiple outcomes,
      including child weight status.

PMID- 30188184
TI  - Supramalleolar Osteotomy Combined With an Intra-articular Osteotomy for the
      Reconstruction of Malunited Medial Impacted Ankle Fractures.
AB  - BACKGROUND:: Malunion of a medial impacted ankle fracture may cause varus ankle
      deformity. This retrospective study examined the use of supramalleolar osteotomy
      combined with an intra-articular osteotomy in patients with malunited medial
      impacted ankle fractures. METHODS:: Twenty-four patients with malunited medial
      impacted ankle fracture were treated between January 2011 and December 2014.
      Using Weber's classification, 10 had type A fractures and 14 had type B, and with
      the AO classification, 20 had 44A2 and 4 had 44B3. All of these patients had
      varus ankle deformity. Supramalleolar osteotomy combined with an intra-articular
      osteotomy was performed. The visual analog scale (VAS) for pain during daily
      activities, the Olerud and Molander Scale and the modified Takakura
      classification stage were used to determine the clinical outcomes and a
      radiographic analysis was performed. RESULTS:: The radiographic parameters,
      including the tibial ankle surface (TAS) angle and talar tilt angle (TTA), showed
      significant differences between the preoperative and follow-up assessments. The
      mean tibial lateral surface (TLS) did not show a significant change. The average
      Olerud and Molander Scale score improved significantly from 56.4 +/- 6.21
      preoperatively to 77.0 +/- 6.11 at the latest follow-up ( P < .01). The mean VAS
      decreased significantly from 6.7 +/- 0.8 preoperatively to 3.1 +/- 0.6 at the
      latest follow-up ( P < .01). No significant difference in the modified Takakura
      classification stage was observed between the preoperative assessment and the
      last follow-up. CONCLUSIONS:: The use of a supramalleolar osteotomy combined with
      an intra-articular osteotomy was an effective option for the treatment of
      malunited medial impacted ankle fractures associated with varus ankle deformity.
      LEVEL OF EVIDENCE:: Level IV, retrospective case series.

PMID- 30188185
TI  - Pullout Strength After Multiple Reinsertions in Radial Bone Fixation.
AB  - BACKGROUND: Due to bone cutting loss from self-tapping screws (STS), progressive
      destruction of bone can occur with each reinsertion during surgery. When
      considering the use of jigs that utilize multiple insertions such as those seen
      in ulnar and radial shortening osteotomy systems, or scenarios where a screw
      needs to be removed and reinserted due to some technical issue, this can be
      concerning, as multiple studies examining the effects of multiple reinsertions
      and the relationship between insertional torque and pullout strength have had
      mixed results. METHODS: Insertional torque and pullout strength were
      experimentally measured following multiple reinsertions of STS for up to 5 total
      insertions for various densities and locations along radial sawbone shafts.
      RESULTS: Torque and pullout strength were significantly greater in middle
      segments of the radial shaft. Our trials corroborate previous literature
      regarding a significant reduction in fixation between 1 and 2 insertions; beyond
      this, there was no significant difference between pullout strength across all
      segment locations as well as bone densities for 3 to 5 insertions. There was a
      moderate to high correlation of insertional torque to pullout strength noted
      across all bone densities and segments (Pearson r = 0.663, P < .001). CONCLUSION:
      While reinsertion of STS between 1 and 2 insertions has been shown to
      significantly differ in pullout strength, beyond this, there does not appear to
      be a significant difference in up to 5 insertions at any specific region of
      radial bone across a range of sawbone densities. Further insertions may be
      considered with caution.

PMID- 30188186
TI  - Coban Method for Removing a Constricting Ring.
AB  - BACKGROUND: Various techniques have been described for removal of a tight
      constricting ring from a finger. A novel procedure is described in this article.
      METHODS: The method is a modification of the string wrap or winding technique. A
      1-inch Coban wrap, lubricant, and pickups are all that is required. RESULTS: The
      author has used this method to remove constricting rings from swollen and
      arthritic fingers in 5 patients. The technique has been successful in all cases,
      and no complications occurred. CONCLUSIONS: The Coban method is a quick, easy,
      and inexpensive technique for ring removal from a finger. The technique should be
      taught to and known by every clinician who treats hand problems.

PMID- 30188187
TI  - Association Between MALAT1 and THRIL Polymorphisms and Precancerous Cervical
      Lesions.
AB  - BACKGROUND: The occurrence of cervical cancer is a complex process, for which
      human papillomavirus (HPV) infection is a risk factor, although not all women
      infected with HPV will develop the disease. Knockout of mammalian lung metastasis
      associated transcript 1 (MALAT1) is associated with increased risk for several
      cancer types, whereas the long non-coding RNA (lncRNA) THRIL is essential for
      induction of tumor necrosis factor-alpha expression, which plays important roles
      in HPV infection. MATERIALS AND METHODS: To investigate the effects of
      polymorphisms in the lncRNAs MALAT1 and THRIL on the susceptibility to
      precancerous cervical lesions, 12 single nucleotide polymorphisms (SNPs) were
      analyzed from 164 cervical precancerous lesion cases and 428 controls. Gene-gene
      and gene-environment interactions and haplotype associations were also evaluated.
      RESULTS: We found a significantly decreased risk of precancerous cervical lesions
      for the THRIL rs7133268 AG genotype (odds ratio adjusted = 0.63, 95% confidence
      interval: 0.42-0.94, p = 0.025). Multifactor dimensionality reduction analysis
      identified a significant two-locus interaction model involved in HPV infection
      and THRIL rs7133268 (training balanced accuracy = 0.6957, testing balanced
      accuracy = 0.6948, cross-validation consistency = 10/10, p = 0.0046). Other SNPs,
      including the two identified for MALAT1, were not significantly related to the
      risk of precancerous cervical lesions. CONCLUSION: Our results suggest that the
      rs7133268 polymorphism of the lncRNA THRIL gene can reduce the genetic
      susceptibility of precancerous cervical lesions and in turn reduce the risk of
      HPV infection.

PMID- 30188188
TI  - Medical Comorbidities and Functional Dependent Living Are Independent Risk
      Factors for Short-Term Complications Following Osteotomy Procedures about the
      Knee.
AB  - Objective To characterize rates and risk factors for adverse events following
      distal femoral osteotomy (DFO), high tibial osteotomy (HTO), and tibial tubercle
      osteotomy (TTO) procedures. Design Patients undergoing DFO, HTO, or TTO
      procedures during 2005 to 2016 were identified in the American College of
      Surgeons National Surgical Quality Improvement Program. Rates of adverse events
      were characterized for each procedure. Demographic, comorbidity, and procedural
      factors were tested for association with occurrence of any adverse events.
      Results A total of 1,083 patients were identified. Of these, 305 (28%) underwent
      DFO, 273 (25%) underwent HTO, and 505 (47%) underwent TTO. Mean ages for patients
      undergoing each procedure were the following: DFO, 51 +/- 23 years; HTO, 40 +/-
      13 years; and TTO, 31 +/- 11 years. The most common comorbidities for DFO were
      hypertension (34%) and smoking (17%); for HTO, hypertension (22%) and smoking
      (21%); and for TTO, smoking (20%) and hypertension (11%). Independent risk
      factors for occurrence of any adverse event were age ?45 years for DFO (odds
      ratio [OR] = 3.1, P < 0.001) and HTO (OR = 2.3, P = 0.029), and body mass index
      >30 for HTO (OR = 2.5, 95% confidence interval = 1.1-5.7, P = 0.031). When all
      osteotomy procedures were analyzed collectively, additional variables including
      diabetes mellitus (OR = 2.2, P = 0.017), chronic obstructive pulmonary disease
      (OR = 5.5, P = 0.003), and dependent functional status (OR = 3.0, P = 0.004) were
      associated with adverse events. Conclusions The total rate of adverse events was
      not independently associated with the type of osteotomy procedure. In addition,
      patients with age >45, diabetes mellitus, chronic obstructive pulmonary disease,
      and dependent functional status have greater odds for adverse events and should
      be counseled and monitored accordingly.

PMID- 30188189
TI  - Management of challenging immune-related gastrointestinal adverse events
      associated with immune checkpoint inhibitors.
AB  - Immune-related gastrointestinal toxicities (irGI) are well-known adverse events
      (AEs) with immune checkpoint inhibitors. The aim of this review was to present
      clinical data from 82 cases to provide information to clinicians who face real
      world challenges among their patients with irGI AEs. The findings of this review
      support the use of the current management guidelines. By analyzing the treatment
      courses and outcomes of all cases identified, our review recommends that
      recurrent cases be treated carefully regardless of the grade of diarrhea at the
      onset of events. Earlier gastroenterology consultation and computed
      tomography/endoscopy diagnosis are essential, especially when an irGI AE recurs
      or worsens during steroid tapering. We would also suggest earlier decision to add
      immunosuppressant agents, particularly for recurrent cases.

PMID- 30188190
TI  - Videourology Abstracts.

PMID- 30188191
TI  - Utilization of Electrodiagnostic Testing for Carpal Tunnel Syndrome by General
      Practitioners Prior to Hand Surgery Consultation.
AB  - BACKGROUND: Carpal tunnel syndrome (CTS) is the most common peripheral
      mononeuropathy and thus is frequently encountered by general practitioners (GPs).
      The aim of this study is to investigate the referral pattern of GPs with regard
      to electrodiagnostic (EDX) testing for suspected CTS prior to hand surgery
      consultation, as well as to investigate the results of EDX testing for suspected
      CTS when requested by GPs prior to evaluation by a hand surgeon. METHODS: We
      retrospectively reviewed patients referred to our hand surgery clinic over a
      consecutive 2-year period for suspected CTS. RESULTS: A total of 403 patients
      were referred to our hand surgery clinic from January 1, 2016, to December 31,
      2017. Of the 403, 295 (73.2%) were referred by GPs. GPs obtained prereferral EDX
      testing in 198 (67.1%) of these patients. EDX testing confirmed their diagnosis
      in 177 patients (89.4%). There were 21 patients (10.6%) identified with normal
      EDX testing and a more likely diagnosis reached based on clinical examination.
      CONCLUSIONS: GPs make up the majority of our referrals for CTS, and they obtain
      EDX testing prior to consultation in two-thirds of referrals. GPs appear to
      accurately utilize EDX testing to confirm their diagnosis prior to referral and
      have a low rate of normal testing where symptoms are more readily explained by an
      alternative diagnosis.

PMID- 30188193
TI  - Impact of Casting and Splinting Manipulations on Below-Dressing Pressures: An
      Experimental Model.
AB  - BACKGROUND: We tested how different applications of casts and splints affect
      underlying below-dressing pressures and how these dressings respond to swelling.
      METHODS: A 3-in polyvinyl chloride pipe with an attached 100 mL saline bag to the
      outer surface was used to simulate a human forearm. A pressure transducer was
      attached to the bag and connected to a monitor providing continuous pressure
      measurements. Either a circumferential fiberglass cast or single-sided plaster
      splint was applied around the bag. To simulate the dressing's compliance to soft
      tissue swelling, change in pressure was measured after 25 mL of saline was
      injected into the bag. Compliance was determined by calculating change in volume
      over change in pressure as volume was added. RESULTS: In our 150 mL model, cast
      bivalving reduced pressure up to 28%, and splitting the cotton padding of a
      splint reduced pressures up to 33%. The mean compliance (ability to accommodate
      swelling) across all volume intervals was 182% greater in a bivalved cast versus
      a cast and 21% greater in a cotton-split splint versus a splint. Below-dressing
      pressure of a tightly wrapped elastic bandage was up to 2.76* greater than a
      medium tension bandage and up to 6.44* greater than a loosely applied bandage. A
      splint with real cotton padding had a 28% greater pressure than a splint with
      synthetic soft-roll padding. CONCLUSIONS: Splitting a dressing, utilizing
      synthetic cotton padding, and applying an elastic bandage cautiously can help
      reduce surface pressures and allow the construct to be more accommodating to soft
      tissue swelling.

PMID- 30188192
TI  - Multivariable Artificial Pancreas for Various Exercise Types and Intensities.
AB  - BACKGROUND: Exercise challenges people with type 1 diabetes in controlling their
      glucose concentration (GC). A multivariable adaptive artificial pancreas (MAAP)
      may lessen the burden. METHODS: The MAAP operates without any user input and
      computes insulin based on continuous glucose monitor and physical activity
      signals. To analyze performance, 18 60-h closed-loop experiments with 96 exercise
      sessions with three different protocols were completed. Each day, the subjects
      completed one resistance and one treadmill exercise (moderate continuous training
      [MCT] or high-intensity interval training [HIIT]). The primary outcome is time
      spent in each glycemic range during the exercise + recovery period. Secondary
      measures include average GC and average change in GC during each exercise
      modality. RESULTS: The GC during exercise + recovery periods were within the
      euglycemic range (70-180 mg/dL) for 69.9% of the time and within a safe glycemic
      range for exercise (70-250 mg/dL) for 93.0% of the time. The exercise sessions
      are defined to begin 30 min before the start of exercise and end 2 h after start
      of exercise. The GC were within the severe hypoglycemia (<55 mg/dL), moderate
      hypoglycemia (55-70 mg/dL), moderate hyperglycemia (180-250 mg/dL), and severe
      hyperglycemia (>250 mg/dL) for 0.9%, 1.3%, 23.1%, and 4.8% of the time,
      respectively. The average GC decline during exercise differed with exercise type
      (P = 0.0097) with a significant difference between the MCT and resistance (P =
      0.0075). To prevent large GC decreases leading to hypoglycemia, MAAP recommended
      carbohydrates in 59% of MCT, 50% of HIIT, and 39% of resistance sessions.
      CONCLUSIONS: A consistent GC decline occurred in exercise and recovery periods,
      which differed with exercise type. The average GC at the start of exercise was
      above target (185.5 +/- 56.6 mg/dL for MCT, 166.9 +/- 61.9 mg/dL for resistance
      training, and 171.7 +/- 41.4 mg/dL HIIT), making a small decrease desirable.
      Hypoglycemic events occurred in 14.6% of exercise sessions and represented only
      2.22% of the exercise and recovery period.

PMID- 30188194
TI  - Sleep Disturbances in COPD are Associated with Heterogeneity of Airway
      Obstruction.
AB  - Individuals with Chronic Obstructive Pulmonary Disease (COPD) experience sleep
      disturbances due to the impact of respiratory symptoms on sleep quality. We
      explored whether sleep disturbances in COPD are linked to heterogeneity of airway
      constriction. The impact of breathing problems on sleep quality was measured in
      consecutive COPD outpatients with the COPD and Asthma Sleep Impact Scale (CASIS)
      questionnaire. Impulse oscillometry technique (IOS) was employed to assess
      heterogeneity of airway constriction. Subjects with a previous or concomitant
      diagnosis of asthma or obstructive sleep apnea (OSA) were excluded. Fifty COPD
      subjects (M/F 40/10; age: 71 +/- 8 yrs, Body Mass Index (BMI): 26.2 +/- 4.7
      kg/m2, Forced Expiratory Volume in the first second (FEV1): 65 +/- 25% predicted;
      mean +/- SD) were enrolled. The mean CASIS score was 36 +/- 3.3, and the R5-R20
      value was 0.2 +/- 0.15 kPa s L-1. The CASIS score was significantly higher in
      subjects with increased R5-R20 (>0.07 kPa s L-1) (39 +/- 24; p = 0.02) compared
      to normal R5-R20 (21 +/- 17). When subjects were categorized on the basis of lung
      function in severely versus non severely obstructed (FEV1 <= or >50% predicted)
      or air trappers versus non air trappers (Residual Volume, RV >= or <120%
      predicted) the CASIS score remained unchanged (for FEV1: 37 +/- 23 versus 33 +/-
      25, respectively, p = 0.61; for RV: 30 +/- 20 versus 40 +/- 23, p = 0.16). Sleep
      disturbances due to COPD symptoms are associated with heterogeneity of airway
      constriction, possibly reflecting peripheral airway dysfunction.

PMID- 30188195
TI  - Basilar Thumb Arthritis: The Utility of Suture-Button Suspensionplasty.
AB  - BACKGROUND: We sought to compare the functional outcomes, radiographic outcomes,
      and complications of trapeziectomy and flexor carpi radialis (FCR) to abductor
      pollicis longus (APL) side-to-side tendon transfer with or without suture-button
      suspensionplasty for thumb basilar joint arthritis. METHODS: Patients treated
      with and without suture-button suspensionplasty were compared over a 6-year
      period. Data were reviewed for complications and functional outcomes, including
      grip and pinch strength, range of motion, and visual analog scale (VAS) pain
      scores. Plain radiographs were independently reviewed at initial presentation and
      at final follow-up, including proximal phalanx length, trapezial space height,
      and trapezial height ratio. RESULTS: Seventy thumb arthroplasties were performed
      in 70 patients. Trapeziectomy with FCR-APL side-to-side tendon transfer was
      performed in 39 patients, and trapeziectomy with FCR-APL side-to-side tendon
      transfer with suture-button suspensionplasty was performed in 31 patients. Mean
      length of follow-up was 28.4 +/- 3.9 and 23.8 +/- 2.6 months, respectively.
      Postoperative grip, oppositional and appositional pinch strength, and VAS pain
      scores improved compared with preoperative values, but were not significantly
      different based on suture-button suspensionplasty. Percentage decline in
      trapezial space ratio was significantly different between groups at 36.7% and
      20.4% for procedures with and without suture-button suspensionplasty,
      respectively indicating that the trapezial space was better maintained within the
      suture suspension cohort. The incidence of postoperative complications, including
      surgical site infection, paresthesias, reoperation, complex regional pain
      syndrome, and symptomatic subsidence, was not significantly different between
      groups. CONCLUSIONS: Trapeziectomy with FCR to APL side-to-side tendon transfer
      with and without suture-button suspensionplasty results in comparable improvement
      in pain, grip strength, and functional parameters. Suture-button suspensionplasty
      results in significantly greater preservation of trapezial space.

PMID- 30188196
TI  - Clinical audit does not work, is quality improvement any better?
AB  - This article reviews the history of clinical audit and appraises its
      effectiveness. It discusses why audit can be ineffective in improving care and
      makes proposals to remove these barriers. The article describes how quality
      improvement and improvement science may offer a better alternative to traditional
      audit. It describes how the Royal College of Emergency Medicine is the first
      specialty society to attempt a national quality improvement programme.

PMID- 30188197
TI  - Emergency medicine myths and misconceptions: evaluating the evidence.
AB  - Medical reversal is common, with rates of reversal of practices that were
      considered standard of care as high as 40%. Unfortunately, many standards of care
      are never tested, but instead are often promoted based on pathophysiological
      explanations or simply being long-established practices. Much of medical practice
      is based on dogma: a set of principles laid down by authority as incontrovertibly
      true. This article evaluates four commonly taught dogmatic practices in emergency
      medicine to determine if they are supported by the medical literature or are
      instead myths and misconceptions: (1) topical anaesthetics inhibit corneal
      healing, (2) treatment of myocardial infarction is MONA (morphine, oxygen,
      nitrates, aspirin), (3) children do not get sprains because their ligaments are
      stronger than bone, and (4) vagal manoeuvres for supraventricular tachycardia
      never work in adults. Medicine is changing all the time, and the best way to
      ensure that one is practicing medicine that is accurate, up to date and not prone
      to being reversed is to always be sceptical and to learn how to read and
      interpret the medical literature.

PMID- 30188198
TI  - Training in emergency medicine.
AB  - One of the key challenges faced in emergency medicine is to provide effective
      training so that clinicians feel valued and supported in the roles they
      undertake. While there are numerous areas of exemplar practice nationally this
      article details two areas of particular focus for the Royal College of Emergency
      Medicine: supporting trainees' return to formal training programmes and
      developing specialty and associate specialist doctors in emergency medicine.

PMID- 30188199
TI  - Leadership in the medical school curriculum: a view from medical students.

PMID- 30188200
TI  - Assessment and management of infected total knee replacements.
AB  - Infection following total knee replacement surgery is a challenging and
      devastating complication. Clinical assessment including history, examination,
      radiographs, blood tests and knee aspirations helps to establish the diagnosis.
      Revision surgery is typically required to eradicate infection and restore
      function. This has traditionally been performed through two-stage revision
      surgery, although single-stage revision surgery is gaining popularity with
      comparable results in carefully selected patients. This article reviews the
      clinical assessment and principles of surgical management of infected total knee
      replacements.

PMID- 30188201
TI  - Robert Daniel Lawrence: diabetic and pioneer of the diabetic clinic.

PMID- 30188202
TI  - What should we do about crowding in emergency departments?
AB  - Our emergency departments have never been under so much pressure. Crowding in
      these departments is both a cause and symptom of this pressure. Crowding kills
      patients and harms staff. It is the most important problem affecting emergency
      departments in the UK. The causes are described and include factors relating to
      input, throughput and output. Interventions aimed at these causes may confer
      benefit, but the most important problem remains unsolved. This is exit block
      caused by lack of beds, and flow through those beds, exacerbated by downgrading
      of capacity in unscheduled care in the evenings, weekends and during holiday
      periods.

PMID- 30188203
TI  - Advanced clinical practitioners in emergency care: past, present and future.
AB  - Developing a consistent and skilled workforce is critical to the sustainability
      of any clinical service. Nurses and paramedics have formed part of the emergency
      care workforce for many years and the extended role of these staff groups has
      supported patient care as the demand has risen and outstripped the capacity of
      the medical staff. In many hospitals and health-care systems, these extended
      roles have developed in response to local demand and case mix, resulting in
      inconsistent role descriptions and lack of transportable qualifications. Even for
      established roles such as emergency nurse practitioners, there is no UK-wide
      defined scope of practice or curriculum to support the role. In 2014 a joint
      working group of the Royal College of Emergency Medicine and Health Education
      England agreed a programme of work to support a sustainable emergency care
      workforce. One stream of that work focused on developing non-medical roles within
      emergency care and in particular the role of the advanced clinical practitioner
      in emergency medicine. Advanced practice has developed in the UK in many
      specialties and the new advanced practice framework from Health Education England
      (2017) allows a cross-discipline understanding of the principles and key aspects
      of advanced practice. However, this framework is naturally generic and does not
      focus on what a practitioner is capable of within a specific clinical area, but
      more on the core capabilities. This article outlines the development of a UK-wide
      curriculum and credentialing process for emergency care advanced clinical
      practitioners and reports on progress to date.

PMID- 30188204
TI  - Hydropneumothorax and intrapulmonary metastases secondary to breast cancer
      recurrence.

PMID- 30188205
TI  - 'Fixing' emergency care: what does it really need?

PMID- 30188206
TI  - Clinical heterogeneity of anti-PM/Scl positive conditions.

PMID- 30188207
TI  - Establishing an ambulatory care service using point-of-care testing diagnostics.
AB  - The use of ambulatory emergency care services in the NHS has been shown to reduce
      the emergency inpatient burden and enhance the overall patient experience, while
      demonstrating a cost saving to the NHS. At the James Paget University Hospital
      point-of-care testing was used as an enabler within an evidence-based lean
      service redesign to successfully set up a novel unit. A 3-month pilot period,
      with limited operational times, showed a dramatic improvement in patient flow
      through the acute medicine pathway, with an equivalent of 59 bed days saved
      during the pilot period. Further expansion of the unit to a dedicated area with
      full 7-day opening allowed a continued improvement in performance. This resulted
      in a mean length of stay of 115 minutes (a 54% reduction from pre-baseline), and
      just 6.1% of an average of 18.1 daily attendances were converted to full
      admission. This demonstrated a clinical, operational and financial benefit,
      allowing improved clinical outcomes.

PMID- 30188208
TI  - Emerging evidence in the delivery of stroke thrombolysis.

PMID- 30188209
TI  - Delirium.

PMID- 30188210
TI  - Squamous cell carcinoma of the palm after chronic organophosphate exposure.

PMID- 30188211
TI  - Lessons from Bawa-Garba and moving forward.

PMID- 30188212
TI  - A system under pressure.
AB  - Activity levels within emergency medicine, and the pressures experienced by
      individual clinicians working within the specialty, continue to increase year on
      year. In 2016-17 there were 18 691 546 attendances at UK emergency departments.
      Attendance numbers continue to increase annually, patients are becoming older and
      more unwell, departments are more crowded and as a result, emergency care
      standard performance figures are deteriorating. This article describes the impact
      of this pressure on the staff working within the emergency department and begins
      to explore the potential for the development of sustainability within the
      existing and future workforce.

PMID- 30188213
TI  - The Nikolsky sign.

PMID- 30188214
TI  - Clinical News.

PMID- 30188215
TI  - Ventriculoperitoneal shunts.

PMID- 30188216
TI  - Autoimmune encephalitis.

PMID- 30188217
TI  - SAHA (vorinostat) facilitates functional polymer-based gene transfection via
      upregulation of ROS and synergizes with TRAIL gene delivery for cancer therapy.
AB  - Non-viral gene delivery is an attractive approach for the treatment of many
      diseases including cancer, benefiting from its safety and large-scale production
      concerns. However, the relatively low transfection efficacy compared with viral
      vectors restricts the clinical applications of non-viral gene vectors. Reactive
      oxygen species (ROS) triggered charge reversal polymers (named B-PDEAEA)
      presented improved transfection efficacy, because of fast release of plasmid DNA
      responding to enhanced oxidative stress in cancer cells. But inadequate
      dissociation can still occur owing to the insufficient intracellular ROS
      generation. Here, we report SAHA (vorinostat), which is a clinical histone
      deacetylase inhibitor and anticancer drug, induces the ROS accumulation in cancer
      cells, and facilitates the charge reversal process of B-PDEAEA and the cellular
      dissociation of the delivered gene from the vectors. As a result, SAHA remarkably
      increases the gene transfection efficacy in an ROS-dependent manner. Importantly,
      SAHA synergizes with B-PDEAEA mediated therapeutic gene TNF-related apoptosis
      inducing ligand (TRAIL) delivery in inducing apoptosis of cancer cells. These
      findings support the first concept of improving the gene delivery efficacy of
      stimuli-responsive vectors through upregulating the cellular ROS via an FDA
      approved anticancer agent. Additionally, combination of SAHA and TRAIL gene
      therapy could be a potential strategy for cancer treatment.

PMID- 30188218
TI  - Circulating Levels of Osteoprotegerin, Osteocalcin and Osteopontin in Patients
      with Rheumatoid Arthritis: A Systematic Review and Meta-Analysis.
AB  - OBJECTIVE: Currently published data regarding the potential role of
      osteoprotegerin (OPG), osteocalcin (OCN) and osteopontin (OPN) for the
      discrimination between rheumatoid arthritis (RA) and osteoarthritis (OA) are
      contradictory. To derive a more precise evaluation, a meta-analysis was
      performed. METHODS: Published literatures comparing plasma/serum OPG, OCN and OPN
      levels between RA group and OA controls were searched in PubMed, Embase and the
      Cochrane Library. The Newcastle-Ottawa Scale was used to assess the study
      quality. Pooled standard mean difference (SMD) with 95% confidence interval (CI)
      was calculated by random-effect model analysis. Heterogeneity test was performed
      by the Q statistic and quantified using I2. RESULTS: Nine studies including 438
      RA patients and 255 OA patients were finally incorporated in the meta-analysis
      after examining title, type, abstracts and full text. The results showed that RA
      patients had higher plasma/serum OPN (pooled SMD = -2.57, 95% CI = -4.72 to 
      0.41) levels when compared to OA patients. No significant difference in
      plasma/serum OPG (pooled SMD = -0.29, 95% CI = -1.07-0.49) and OCN (pooled SMD = 
      0.09, 95% CI = -0.48-0.31) levels were found between RA patients and OA patients.
      Subgroup analysis indicated that plasma/serum OPG levels had no significant
      differences between RA patients and OA patients in Europe and Asian. CONCLUSIONS:
      Overall, there is no significant difference in circulating OPG and OCN levels
      between RA patients and OA patients. However, plasma/serum OPN level is
      significantly higher in RA patients compared with OA patients.

PMID- 30188219
TI  - Does Adherence to Domiciliary NIMV Decrease the Subsequent Hospitalizations Rates
      and Cost for Patients Diagnosed with COPD?
AB  - Domiciliary noninvasive mechanical ventilation (NIMV) is used for treating
      patients with hypercapnic chronic obstructive pulmonary disease (COPD). We aimed
      to evaluate the association between adherence to the treatment and subsequent
      hospitalizations and costs. Data from 54 (27 adherent; 27 non-adherent) patients
      with COPD who were undergoing NIMV treatment at home for 6 months. We assessed
      adherence based on digitally recorded data and checked hospital records for
      clinical and laboratory data, rehospitalization rates, and costs during the
      following 6 months. Nocturnal NIMV usage, mean daily usage of the device, and
      time to first hospitalization were higher in the treatment-adherent group (p <
      .001, p < .001, and p=.006, respectively). The percentage of active smokers,
      device leaks above 30 L/min, length of hospital stay, rehospitalization rates,
      and costs were significantly higher in the treatment-non-adherent group (p = 05,
      p = 006, p = 004, p = 006, and p = 01, respectively). The most frequent reasons
      for not using NIMV in the treatment-non-adherent group were a decreased need, dry
      mouth, mask incompatibility, and gastrointestinal complaints. Adherence to NIMV
      treatment decreases the subsequent hospitalizations rates and noncompliance leads
      to complications. Findings of this study may help physicians in convincing
      patients diagnosed with COPD of the need for correct NIMV use to prevent
      hospitalizations and reduce the costs of COPD treatment.

PMID- 30188220
TI  - Dietary nitrate improved exercise capacity in COPD but not blood pressure or
      pulmonary function: a 2 week, double-blind randomised, placebo-controlled
      crossover trial.
AB  - Dietary nitrate may improve exercise tolerance in some healthy and clinical
      populations. Existing data regarding dietary nitrate in COPD is inconsistent. We
      conducted a 14d double-blind, randomised, placebo-controlled, crossover trial of
      daily nitrate-rich beetroot juice (BRJ; 12.9 mmol) versus nitrate-depleted BRJ
      (PL; 0.5 mmol). At baseline and after each condition, we assessed functional
      capacity (incremental shuttle walk test; ISWT), ambulatory blood pressure,
      pulmonary function, quality of life as well as exhaled nitric oxide (eNO), and
      plasma nitrate/nitrite (NOx). Eight subjects with COPD completed the trial. BRJ
      supplementation was associated with significantly increased NOx (p < .05) and a
      14.6% increase in ISWT distance (+56 m, p = .00004) as well as a trend towards
      increased eNO compared to PL. There was no other differences. Dietary nitrate
      appears to have ergogenic effect in subjects with mild-moderate COPD. This effect
      does not appear to be related to altering blood pressure or pulmonary function.

PMID- 30188222
TI  - The stimulant higenamine in weight loss and sports supplements.
AB  - BACKGROUND: Higenamine is a stimulant with cardiovascular properties recently
      prohibited in sport by the World Anti-Doping Agency (WADA). Higenamine is also a
      natural constituent of several traditional botanical remedies and is listed as an
      ingredient in weight loss and sports supplements sold over-the-counter in the
      United States. OBJECTIVES: We analyzed dietary supplements available for sale in
      the United States prior to WADA's prohibition of higenamine in sport for the
      presence and quantity of higenamine. METHODS: All supplements labeled as
      containing higenamine or a synonym (i.e., norcoclaurine or demethylcoclaurine)
      available for sale in the United States were identified. For each brand, one
      sample was analyzed by NSF International (Ann Arbor, MI) and one sample by the
      Netherland's National Institute for Public Health and the Environment (RIVM). NSF
      International carried out qualitative and quantitative analyses using ultra high
      performance liquid chromatography (UHPLC) with tandem mass spectrometry. RIVM
      carried out qualitative analysis using UHPLC quadrupole time of flight mass
      spectrometry for an independent confirmation of identity. RESULTS: Twenty-four
      products were analyzed. The majority of supplements were marketed as either
      weight loss (11/24; 46%) or sports/energy supplements (11/24; 46%); two brands
      did not list a labeled indication. The quantity of higenamine (+/-95% CI) ranged
      from trace amounts to 62 +/- 6.0 mg per serving. Consumers could be exposed to up
      to 110 +/- 11 mg of higenamine per day when following recommended serving sizes
      provided on the label. Five products (5/24; 21%) listed an amount of higenamine,
      but none were accurately labeled; the quantity in these supplements ranged from
      <0.01% to 200% of the quantity listed on the label. CONCLUSION: Dosages of up to
      62 +/- 6.0 mg per serving of the stimulant higenamine were found in dietary
      supplements sold in the United States.

PMID- 30188221
TI  - Mussel adhesive Protein-conjugated Vitronectin (fp-151-VT) Induces Anti
      inflammatory Activity on LPS-stimulated Macrophages and UVB-irradiated
      Keratinocytes.
AB  - BACKGROUND: Skin inflammation and dermal injuries are a major clinical problem
      because current therapies are limited to treating established scars, and there is
      a poor understanding of healing mechanisms. Mussel adhesive proteins (MAPs) have
      great potential in many tissue engineering and biomedical applications. It has
      been successfully demonstrated that the redesigned hybrid type MAP (fp-151) can
      be utilized as a promising adhesive biomaterial. The aim of this study was to
      develop a novel recombinant protein using fp-151 and vitronectin (VT) and to
      elucidate the anti-inflammatory effects of this recombinant protein on
      macrophages and keratinocytes. METHODS: Lipopolysaccharide (LPS) was used to
      stimulate macrophages and UVB was used to stimulate keratinocytes. Inducible
      nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 were analyzed by Western
      Blot. Inflammatory cytokines and NO and ROS production were analyzed. RESULT: In
      macrophages stimulated by LPS, expression of the inflammatory factors iNOS, COX
      2, and NO production increased, while the r-fp-151-VT-treated groups had
      suppressed expression of iNOS, COX-2, and NO production in a dose-dependent
      manner. In addition, keratinocytes stimulated by UVB and treated with r-fp-151-VT
      had reduced expression of iNOS and COX-2. Interestingly, in UVB-irradiated
      keratinocytes, inflammatory cytokines, such as interleukin (IL)-1b, IL-6, and
      tumor necrosis factor (TNF)-a, were significantly reduced by r-fp-151-VT
      treatment. CONCLUSIONS: These results suggest that the anti-inflammatory activity
      of r-fp-151-VT was more effective in keratinocytes, suggesting that it can be
      used as a therapeutic agent to treat skin inflammation.

PMID- 30188223
TI  - Clinicopathologic and genetic spectrum of infantile B-lymphoblastic leukemia: a
      multi-institutional study.
AB  - Acute lymphoblastic leukemia (ALL) in infants <1-year-old is biologically
      different from ALL in older children. Although KMT2A rearrangement is the
      predominant genetic signature in infantile B-ALL, disease course is heterogenous,
      behaving more aggressively in younger infants. We investigated
      clinicopathological differences throughout the first year to understand the
      transition to pediatric B-ALL. In a multi-institutional review involving four
      medical institutions, 54 cases of infantile B-ALL were identified. Patients were
      divided into congenital and non-congenital groups with multiple age subgroups.
      Male predominance was seen in congenital cases compared to female in non
      congenital cases. There were decreasing trends of hyperleukocytosis, central
      nervous system involvement, KMT2A rearrangements, lineage switch, and mortality,
      versus increasing trends of CD10 expression and non-KMT2A abnormalities.
      Statistically significant differences emerged at 3 and 9 months, the latter was
      not previously described. Poor-prognostic risk factors decreased with age, the
      last trimester of infantile B-ALL essentially merging with pediatric B-ALL.

PMID- 30188224
TI  - The role of radiotherapy in the management of primary cardiac lymphoma a case
      report and the literature review.

PMID- 30188225
TI  - Maintenance rituximab in newly diagnosed mantle cell lymphoma patients: a real
      world analysis from the Czech lymphoma study group registry?.
AB  - We analyzed 495 MCL patients from the Czech Lymphoma Study Group data registry.
      With the median follow-up of 4.4 years, 51.7% patients progressed or relapsed and
      34.1% died. Five-year overall survival reached 65.3% and five-year progression
      free survival 44.1% of the patients. Maintenance rituximab (MR) after first line
      therapy improved overall and progression free survival compared to the patients
      under observation only (both p < .001). Elevated beta-2-microglobulin (p = .003),
      presence of systemic symptoms (p = .002), ECOG >0 (p = .003), age (p = .014), and
      MIPI (p < .001) were associated with MR failure. Patients who did not achieve
      complete remission have had two-fold higher risk of MR failure (p < .001).
      Autologous stem cell transplant reduced the risk of MR failure by 69% (p < .001).
      The MIPI and the beta-2-microglobulin were identified as independent predictors
      of MR failure (p = .02 and p = .03, respectively). Patients who
      relapsed/progressed on MR reached shorter OS calculated from the MR start
      compared to patients without failure (HR = 15.0; p < .001).

PMID- 30188226
TI  - Cryptococcus neoformans infections in patients with lymphoproliferative
      neoplasms.
AB  - Cryptococcosis is a rare opportunistic infection increasingly associated with
      lymphoproliferative disorders. The clinical course and outcomes in these patients
      have not been extensively studied. We retrospectively reviewed charts of adult
      patients with lymphoproliferative disorders diagnosed with cryptococcal
      infections. A total of 34 patients were identified; 31 (91%) had a B-cell
      neoplasm and 3 (9%) had a T-cell neoplasm. The most frequent clinical syndrome
      was disseminated cryptococcal infection (38%), followed by pneumonia (29%). 74%
      received prior chemotherapy and the overall mortality in this group was nearly
      six-fold higher than chemotherapy naive patients; 26% were chemotherapy naive.
      After a median follow-up of nine months from the date of infection, 24 patients
      had died (71%). The overall mortality at 30-days and one year was 18% and 46%,
      respectively. The high mortality warrants future studies to identify those at
      highest risk. Clinicians should remain vigilant as early diagnosis and treatment
      are of utmost importance.

PMID- 30188227
TI  - Associations between the peripheral blood Wilms tumor gene 1 level and both bone
      marrow blast cells and the prognosis in patients with myelodysplastic syndrome.
AB  - Wilms tumor gene 1 (WT1) is highly expressed in myelodysplastic syndrome (MDS)
      cells and is known to reflect the tumor burden in MDS. We evaluated the
      usefulness of WT1 mRNA levels for predicting the prognosis of MDS. At diagnosis,
      WT1 levels were strongly correlated with the percentage of blasts calculated
      based on non-erythroid cells, but not with that based on all nucleated cells (r =
      0.57, p < .05 vs r = 0.42, p = .13). Among the allogeneic transplant recipients,
      the presence of two consecutive WT1 levels >=100 copies/MUg RNA with a median
      interval of one month was associated with a 77.8% relapse rate at nine months
      from the first detection of a high WT1 level, and the median time to relapse was
      only 114 [36-257] days. WT1 levels at diagnosis were correlated with known
      prognostic factors. In addition, the presence of two consecutive high WT1 levels
      after allogeneic transplantation may predict early relapse of MDS.

PMID- 30188228
TI  - Role of Autopsy in Elective Termination of Pregnancy for Fetal Anomaly (ETOPFA):
      A Study from a Tertiary Care Hospital in India.
AB  - OBJECTIVE: To evaluate the fetal anomalies in all the patients who underwent
      elective termination of pregnancy for fetal anomalies (ETOPFA) before 20 weeks of
      gestation and to compare prenatal diagnosis with final diagnosis made after
      autopsy. METHODOLOGY: Prospective study done in a tertiary care hospital in India
      over a period of two years which include 252 women who underwent ETOPFA. The
      prenatal diagnosis was compared with final diagnosis made after autopsy. RESULTS:
      In 75.4% of cases autopsy findings were concordant with prenatal diagnosis where
      as in 21.6% of cases, additional findings were added. In 2.9 % of cases prenatal
      diagnosis was not confirmed by autopsy and found to be discordant. CONCLUSIONS:
      Autopsy plays an important role in completing the final diagnosis along with
      verification of prenatal diagnosis. To avoid discrepancy especially in cases of
      severe oligohydramnios, MRI or amnioinfusion could be offered for conformation of
      the diagnosis before offering ETOPFA.

PMID- 30188229
TI  - The risk of tuberculosis in cancer patients is greatest in lymphoma and
      myelodysplastic syndrome/myeloproliferative neoplasm: a large population-based
      cohort study.
AB  - Patients with cancer are at high risk for tuberculosis (TB). This study combined
      the Israeli databases of cancer and TB and examined the development of TB among
      all newly diagnosed cancer cases from 1993 to 2013. Patients were classified into
      groups according to their different malignancies. Among 495,335 cancer patients,
      335 developed TB following cancer diagnosis. The cumulative incidence of TB
      following cancer diagnosis was highest among MDS/MPN (148.8/100,000 patients) and
      lymphoma (154.1/100,000 patients) (p = .023). The HR of TB following cancer among
      hematologic patients was 2.51 (p < .001), relative to patients with in situ
      carcinomas/skin cancer and highest among MDS/MPN and lymphoma patients (2.74, p =
      .012 and 2.70, p < .001, respectively). Among lymphoma patients, a significant
      increased HR was found only among NHL patients (2.72, p < .001). The limitations
      include lack of information regarding risk factors for TB and of anti-cancer
      treatments. In conclusion, these data may encourage a heightened awareness for TB
      among patients with a background of lymphoma and MDS/MPN.

PMID- 30188230
TI  - IL7R overexpression in adult acute lymphoblastic leukemia is associated to
      JAK/STAT pathway mutations and identifies patients who could benefit from
      targeted therapies.

PMID- 30188231
TI  - Cost-effectiveness of pembrolizumab in combination with chemotherapy in the 1st
      line treatment of non-squamous NSCLC in the US.
AB  - AIMS: To describe cost-effectiveness of pembrolizumab plus platinum and
      pemetrexed chemotherapy in metastatic, non-squamous, NSCLC patients in the US.
      MATERIALS AND METHODS: A model is developed utilizing partitioned survival
      analysis to estimate the cost-effectiveness of KEYNOTE-189 trial comparators
      pembrolizumab + chemotherapy (carboplatin/cisplatin + pemetrexed) vs chemotherapy
      alone. Clinical efficacy, treatment utilization, health utility, and safety data
      are derived from the trial and projected over 20 years. For extrapolating
      survival beyond the trial, a novel SEER population-data approach is applied
      (primary analysis), with separate estimation via traditional parametric
      extrapolation methods. Costs for drugs and non-drug disease management are also
      incorporated. Based on an indirect treatment comparison, cost-effectiveness of
      pembrolizumab + chemotherapy vs pembrolizumab monotherapy is evaluated for
      patients with programmed death-ligand 1 (PD-L1) >= 50%. RESULTS: In the full non
      squamous population, pembrolizumab + chemotherapy is projected to increase life
      expectancy by 2.04 years vs chemotherapy (3.96 vs 1.92), for an approximate
      doubling of life years. Resultant incremental cost-effectiveness ratios (ICERs)
      are $104,823/QALY and $87,242/life year. In patients with PD-L1 >= 50% and 1-49%,
      life expectancy is more than doubled (4.53 vs 1.88 years) and (4.87 vs 2.01
      years), with a 32% (2.60 vs 1.97 years) increase in PD-L1 < 1% patients.
      Corresponding incremental costs/quality-adjusted life year (QALY) are $103,402,
      $66,837, and $183,529 for PD-L1 >= 50%, 1-49%, and <1% groups, respectively.
      Versus pembrolizumab monotherapy in PD-L1 >= 50% patients, representing current
      standard of care, pembrolizumab + chemotherapy increases life expectancy by 65%
      (4.53 vs 2.74 years) at an ICER of $147,365/QALY. LIMITATIONS AND CONCLUSIONS:
      The addition of pembrolizumab to chemotherapy is projected to extend life
      expectancy to a point not previously seen in previously untreated metastatic non
      squamous NSCLC. Although ICERs vary by sub-group and comparator, results suggest
      pembrolizumab + chemotherapy yields ICERs near, or in most cases, well below a 3
      times US per capita GDP threshold of $180,000/QALY, and may be a cost-effective
      first-line treatment for metastatic non-squamous NSCLC patients.

PMID- 30188232
TI  - Circulating microRNAs expression profile in newly diagnosed and imatinib treated
      chronic phase - chronic myeloid leukemia.
AB  - Chronic myeloid leukemia (CML) is a stem cell derived malignant disorder result
      of translocation t(9;22)(q34;q11) called Philadelphia chromosome (Ph+). microRNAS
      (miRNAs) are involved in several biological processes, altering the progression
      of various pathologies, including CML. This study evaluated whether circulating
      miRNAs display differential expression profiles in peripheral blood of CML
      Chronic Phase (CML-CP) patients newly diagnosed in comparison with CML-CP treated
      with imatinib. We obtained peripheral blood samples from CML-CP Ph+ patients
      divided among group 1 (untreated newly diagnosed) and group 2 (treated with
      imatinib). A pool of total leukocytes from healthy donors was considered as
      control group. Expression analyses were performed for 768 miRNAs by RT-qPCR
      array. Bioinformatic tools were used to identify significant pathways and
      interaction networks. We found 80 deregulated miRNAs between the groups and,
      according to bioinformatic analysis, they are involved in different pathways,
      including molecular mechanisms of cancer. The study allows better understanding
      of disease molecular behavior, and it is useful for possible monitoring CML
      treatment and prognostic biomarkers identification.

PMID- 30188233
TI  - Content Validity of the Parentship Protocol: A Multidimensional Intervention for
      Parents of Adolescents with High-Functioning Autism Spectrum Disorder.
AB  - : The Parentship protocol is a short-term intervention program in occupational
      therapy for parents of adolescents with High-Functioning Autism Spectrum Disorder
      (HFASD). Its purpose is to promote parental resilience and enhance adolescents'
      participation in daily life. AIMS: To explore and analyze the perceptions of
      occupational therapists and parents of individuals with HFASD, regarding the
      content of the protocol and its theoretical framework. METHODS: Implementation of
      a phenomenological qualitative approach using two focus groups (six occupational
      therapists and five parents). A transcript-based analysis was used for analyzing
      the data. RESULTS: The degree of agreement regarding the potential purposes and
      contents of the protocol was high. In addition, nine themes were raised and led
      to changes and additions in the protocol. CONCLUSIONS: The study provided support
      for content validity and acceptability of the Parentship protocol. Future
      research should test the feasibility of this new intervention program.

PMID- 30188234
TI  - A real-world analysis of healthcare costs and relative risk of hyperprolactinemia
      associated with antipsychotic treatments in the United States.
AB  - AIMS: Antipsychotic medications are associated with an increased risk of
      hyperprolactinemia, but differ in their propensity to cause this complication.
      This study aimed to assess the economic burden of hyperprolactinemia, and to
      compare its risk among adult patients using atypical antipsychotics (AAs) with a
      mechanism of action associated with no/low vs high/moderate prolactin elevation.
      METHODS: This retrospective cohort study was based on US Commercial and Medicaid
      claims databases. Healthcare costs were compared between matched
      hyperprolactinemia and hyperprolactinemia-free cohorts using a two-part model.
      Risk of hyperprolactinemia was compared between patients receiving AAs with a
      mechanism of action associated with no/low (no/low prolactin elevation cohort) vs
      high/moderate prolactin elevation (high/moderate prolactin cohort) using logistic
      regression. RESULTS: In the commercially insured sample, compared to the
      hyperprolactinemia-free cohort (n = 499), the hyperprolactinemia cohort (n = 499)
      was associated with incremental total healthcare costs of $5,732 ($20,081 vs
      $14,349; p = .004), and incremental medical costs of $3,861 ($13,218 vs $9,357; p
      = .040), mainly driven by hyperprolactinemia-related costs. In the Medicaid
      insured sample, compared to the hyperprolactinemia-free cohort, the
      hyperprolactinemia cohort was associated with incremental total healthcare costs
      of $10,773 ($30,763 vs $19,990; p = .004), and incremental medical costs of
      $9,246 ($20,859 vs $11,613; p = .004), mainly driven by hyperprolactinemia
      related and mental health-related costs. The odds of hyperprolactinemia in the
      no/low prolactin elevation cohort were 4-5-times lower than that in the
      high/moderate prolactin elevation cohort (odds ratio =0.21; p < .001).
      LIMITATIONS: Hyperprolactinemia may be under-reported in claims data.
      CONCLUSIONS: Hyperprolactinemia is associated with substantial healthcare costs.
      AAs associated with no/low prolactin elevation reduce the risk of
      hyperprolactinemia by 4-5-times compared to AAs associated with moderate/high
      prolactin elevation. Treatment options with minimal impact on prolactin levels
      may contribute to reducing hyperprolactinemia burden in AA-treated patients.

PMID- 30188236
TI  - Prognostic impact of serum soluble interleukin-2 receptor level at diagnosis in
      elderly patients with diffuse large B-cell lymphoma treated with R-CHOP.
AB  - Diffuse large B-cell lymphoma (DLBCL) is a clinically heterogeneous disease. To
      evaluate the clinical relevance of the serum soluble interleukin-2 receptor (sIL
      2R) level, we retrospectively analyzed 178 patients aged >=60 years who were
      newly diagnosed with DLBCL. We determined the cutoff value of the sIL-2R level to
      be 1280 U/mL using the area under the receiver operating characteristic curve.
      The high sIL-2R group exhibited significantly inferior 5-year progression-free
      survival (PFS) (36.2% vs. 86.1%, p < .001) and 5-year overall survival (OS)
      (49.7% s. 83.8%, p < .001) than the low sIL-2R group. Multivariate analysis
      revealed that a high sIL-2R level was a significant prognostic factor for PFS and
      OS (hazard ratio [HR]: 5.65, p < .001 and HR: 2.99, p = .001, respectively). This
      study showed that measurement of the sIL-2R level at diagnosis is clinically
      beneficial for identifying elderly patients with DLBCL who have a poor prognosis.

PMID- 30188235
TI  - Effects of the Affordable Care Act on Health Care Access and Self-Assessed Health
      After 3 Years.
AB  - Using data from the Behavioral Risk Factor Surveillance System, we examine the
      causal impact of the Affordable Care Act on health-related outcomes after 3
      years. We estimate difference-in-difference-in-differences models that exploit
      variation in treatment intensity from 2 sources: (1) local area prereform
      uninsured rates from 2013 and (2) state participation in the Medicaid expansion.
      Including the third postreform year leads to 2 important insights. First, gains
      in health insurance coverage and access to care from the policy continued to
      increase in the third year. Second, an improvement in the probability of
      reporting excellent health emerged in the third year, with the effect being
      largely driven by the non-Medicaid expansions components of the policy.

PMID- 30188237
TI  - Can rituximab unlock the innate potential of checkpoint blockade in the CNS?

PMID- 30188238
TI  - Bilateral cystoid macular edema in a patient with chronic lymphocytic leukemia
      treated with ibrutinib.

PMID- 30188239
TI  - Joint Position Statement on Degree Requirements for Paramedics.
AB  - The National Association of EMS Educators, the National EMS Management
      Association, and the International Association of Flight and Critical Care
      Paramedics believe the time has come for paramedics to be trained through a
      formal education process that culminates with an associate degree. Once
      implemented a degree requirement will improve the care delivered by paramedics
      and enhance paramedicine as a heath profession.

PMID- 30188240
TI  - Comparison of clinical features and survival between young and old chronic
      lymphocytic leukemia patients: a single center study from Turkey.
AB  - We aimed to investigate whether the clinical characteristics, the rate of
      treatment demand and survival differ between chronic lymphocytic leukemia (CLL)
      patients <65 years (y) and >=65 y. Sixty three (46%) patients were <65 y and 74
      (54%) were >=65 y. 28.6% (18/63) of the patients <65 required treatment, while
      this rate was 44.6% (33/74) for patients >=65 y (p > .05). The probability of
      overall survival (OS) was 90 vs. 51% in patients <65 y and >=65 y (p = .016). In
      univariate analysis, the age affected OS (p = .04, HR: 0.212, CI: 0.047-0.946).
      In subgroup analysis, in treated patients, the probability of OS was 73 vs. 49%
      in patients <65 y and >=65 y (p = .389). The survival difference between the
      young and old patients is too high to be ignored and age seems to affect the
      outcome of CLL patients.

PMID- 30188241
TI  - Interfacility Transport of the Pregnant Patient: A 5-year Retrospective Review of
      a Single Critical Care Transport Program.
AB  - INTRODUCTION: Interfacility transport of the pregnant patient poses a challenge
      for prehospital providers as it is an infrequent but potentially high acuity
      encounter. Knowledge of clinically significant events (CSEs) that occur during
      these transports is important both to optimize patient safety and also to help
      enhance crew training and preparedness. This study evaluated a critical care
      transport program's 5-year longitudinal experience transporting pregnant patients
      by ground and air, and described CSEs that occurred during the out-of-hospital
      phase of care. METHODS: This study was a retrospective review of pregnant
      patients transported by a single critical care transport system into and within a
      large academic healthcare system. Patients who were pregnant, and were
      transported from a referring facility to one of the 2 receiving centers within
      Johns Hopkins Health System between January 1, 2012 and December 31, 2016 were
      included in this study. The primary outcome of interest was the occurrence of a
      predefined clinically significant event (CSE) during transport, while a secondary
      outcome of interest was the indication for transfer. RESULTS: During the study
      period 1,223 pregnant patients were transported by our critical care transport
      service. There were 1,101 patients who met inclusion criteria; 693 (62.9%) of
      whom were transported by ground and 408 (37.1%) who were transported by rotor
      wing aircraft. The top 3 indications for transfer comprised 71.4% of all patients
      and included; preterm labor, hypertensive disorder of pregnancy, and other
      maternal life threatening disorder. The most common events that occurred across
      all transports were: exacerbation of hypertensive disease requiring intervention
      (4.5%), hypotension (1.3%), and altered mental status (0.2%). CONCLUSIONS:
      Incidence of CSEs during the interfacility transport of pregnant patients within
      our critical care transport system is low (6.0%). Knowledge of the clinically
      significant events that occur during EMS transport is a vital component of
      ensuring system quality and optimizing patient safety. This data can be used to
      augment and focus provider education and training to mitigate and optimize
      response to future events.

PMID- 30188242
TI  - Giant Ovarian Lymphangioma: Case Report and Review of the Literature.
AB  - INTRODUCTION: Lymphangiomas are benign tumors/malformations, characterized by
      proliferation of the lymphatic vessels. They may arise anywhere, although the
      most common localizations are the head-neck region and the axilla. To date, only
      21 cases of lymphangioma of the ovary in a 60-year literature survey have been
      reported. CASE REPORT: A 16-year-old female patient with long standing abdominal
      distension had 40 cm * 15 cm * 29 cm ovarian lymphangioma. CONCLUSIONS: Our case
      highlights that lymphangiomas can occur in the adolescent population and should
      be added to the differential diagnosis of ovarian masses in this age group.

PMID- 30188243
TI  - Introduction of ASP President 2017 - 2018, Dr. Susan Perkins.

PMID- 30188245
TI  - Item-specific and relational processing both improve recall accuracy in the DRM
      paradigm.
AB  - Using the Deese-Roediger-McDermott (DRM) paradigm, Huff and Bodner found that
      both item-specific and relational variants of a task improved correct
      recognition, but only the item-specific variants reduced false recognition,
      relative to a read-control condition. Here, we examined the outcome pattern when
      memory was tested using free recall, using the same item-specific versus
      relational task variants across three experiments as our previous study
      (processing instructions, pleasantness ratings, anagram generation). The outcome
      pattern in recall was similar to recognition, except relational processing at
      study actually reduced the DRM illusion, though not as much as item-specific
      processing. To reconcile this task difference, we suggest that the memory
      information laid down during relational encoding enhances the familiarity of the
      critical items at test. To the extent that familiarity is used less as a basis
      for responding in free recall than in recognition, relational processing
      ironically reduces rather than increases the DRM illusion in recall.

PMID- 30188244
TI  - Value of Information Choices that Influence Estimates: A Systematic Review of
      Prevailing Considerations.
AB  - BACKGROUND: Although value of information (VOI) analyses are increasingly
      advocated and used for research prioritization and reimbursement decisions, the
      interpretation and usefulness of VOI outcomes depend critically on the underlying
      choices and assumptions used in the analysis. In this article, we present a
      structured overview of all items reported in literature to potentially influence
      VOI outcomes. Use of this overview increases awareness and transparency of
      choices and assumptions underpinning VOI outcomes. METHODS: A systematic
      literature review was performed to identify aspects of VOI analyses that were
      found to potentially influence VOI outcomes. Identified aspects were grouped to
      develop a structured overview. Explanations were defined for all items included
      in the overview. RESULTS: We retrieved 687 unique papers, of which 71 original
      papers and 8 reviews were included. In the full text of these 79 papers, 16
      aspects were found that may influence VOI outcomes. These aspects related to the
      underlying evidence (bias, synthesis, heterogeneity, correlation), uncertainty
      (structural, future pricing), model (relevance, approach, population), choices in
      VOI calculation (estimation technique, implementation level, population size,
      perspective), and aspects specifically for assessing the value of future study
      designs (reversal costs, efficient estimator). These aspects were aggregated into
      7 items to provide a structured overview. CONCLUSION: The developed overview
      should increase awareness of key choices underlying VOI analysis and facilitate
      structured reporting of such choices and interpretation of the ensuing VOI
      outcomes by researchers and policy makers. Use of this overview should improve
      prioritization and reimbursement decisions.

PMID- 30188246
TI  - How does simulation of an observed external body state influence categorisation
      of an easily graspable object?
AB  - Several works have provided evidence of a resonant motor effect while observing a
      hand interacting with painful stimuli. The aim of this work is to show that
      participants are sensitive to the observation of an injured hand when they have
      to categorise an easily graspable object with their own hand. In Experiment 1,
      participants indicated whether or not photographs of objects (graspable or non
      graspable, left or right oriented) could be grasped with their dominant hand, by
      tapping a key on a keyboard. Target objects were preceded by primes consisting of
      photographs of hands (injured vs healthy) in a grasping posture (power grasp).
      Experiment 2 consisted of two phases: In the first phase, participants had to
      categorise square or circle shapes. After their response (Group 1: tapping a key
      vs Group 2: constricting a hand grip), photograph of two types of hand (injured
      vs healthy) was displayed on the computer screen. In the second phase,
      participants had to indicate whether objects could be easily grasped with their
      dominant hand. Target objects were preceded by primes (square and circle) as
      shown in the first phase. Results show that response times were slower when the
      graspable target objects were right oriented and preceded by the photograph or a
      geometric shape associated with an injured hand. This response delay was
      accentuated in the handgrip condition. These results highlight that the view of
      an injured hand activates motor programme and pain mechanisms associated with
      participants relative to the consequences of the simulated grasping action.

PMID- 30188247
TI  - Photo-crosslinked and esterase-sensitive polymersome for improved antitumor
      effect of water-soluble chemotherapeutics.
AB  - AIM: To meet the requirements on both delivery stability during blood circulation
      and fast intracellular release for water-soluble chemotherapeutics encapsulated
      in polymersomes. MATERIALS & METHODS: A shell photo-crosslinked and esterase
      sensitive polymersome (C-PEAMP-D) was constructed based on amphiphilic
      polyphosphazene PEAMP containing 2-aminoethyl methacrylate. RESULTS: The leakage
      of doxorubicin hydrochloride (DOX.HCl) was significantly inhibited from 42.27 to
      26.64% in 10 h and the accelerated intracellular DOX.HCl release occurred
      responsively to the esterase at high concentration in cancer cells. Consequently,
      C-PEAMP-D achieved better antitumor efficiency when compared with free DOX.HCl
      and uncrosslinked PEAMP vesicle. CONCLUSION: We provided a strategy to conquer
      drug leakage in systemic circulation and trigger enzyme-sensitive drug release
      inside cancer cells for improving oncotherapy outcome of water-soluble
      chemotherapeutics.

PMID- 30188248
TI  - The potential value of nanomedicine and novel oral dosage forms in the treatment
      of HIV.

PMID- 30188249
TI  - Collegiate baseball players with more optimal functional movement patterns
      demonstrate better athletic performance in speed and agility.
AB  - Sports injuries are common among baseball players and may result in abnormal
      movement patterns, increased risks of future injury, and unsatisfactory
      performance. The Functional Movement Screen (FMSTM) has been developed to detect
      abnormal functional movement patterns and can be used for predicting risks of
      sports injury. However, whether FMSTM scores are associated with athletic
      performance remains unclear. The goal of this study was to determine the
      association between functional movements and athletic performance in elite
      baseball players. Core stability, muscular strength and flexibility of the lower
      extremities, and FMSTM, as well as athletic performance in sprinting, agility,
      and balance tests were assessed in 52 male collegiate Division I baseball players
      placed into two groups based on FMSTM scores. The high-scoring group demonstrated
      better athletic performance than the low-scoring group, with a shorter duration
      of the agility test. No group differences were found in core stability, muscular
      strength, or muscle flexibility, except for rectus femoris flexibility. Thus, the
      FMSTM score is associated with sprinting and agility performance in elite
      baseball players. These findings indicate that the FMSTM may have a role in
      predicting athletic performance and thereby help determine the goals of training
      regimens or return-to-play strategies.

PMID- 30188250
TI  - Prosecution of Child Sexual Abuse Cases Involving Preschool-Aged Children: A
      Study of Swedish Cases from 2010 to 2014.
AB  - Alleged child sexual abuse against preschool-aged children is often considered
      one of the most challenging cases for a prosecutor to handle. The aim of the
      current study was to examine differences between prosecuted and discontinued
      cases of alleged sexual abuse of preschool-aged children. Data from Swedish
      criminal cases of alleged sexual abuse of children ages 2-6 issued from 2010 to
      2014 were analyzed (N = 130). Prosecuted cases were more likely to contain
      forensic evidence (documentation of abuse, corroborative DNA evidence, or a
      corroborative medical examination), or a confession from the suspect, while such
      evidence was not available in any discontinued case. Furthermore, cases where the
      child was older, where the prosecutor had decided to conduct an interview with
      the child, and where there was more than one alleged victim were more likely to
      be prosecuted. Factors that were associated with a decreased likelihood of
      prosecution were ongoing custody disputes between parents, foster care placements
      prior to the abuse, and if the report concerned a boy. Boys and younger children
      were also less likely to be interviewed. The results suggest that prosecution of
      sexual abuse cases involving preschool-aged children remains difficult and that
      there is room for improvements in these investigations.

PMID- 30188251
TI  - Low-Level Laser Therapy and World Association for Laser Therapy Dosage
      Recommendations in Musculoskeletal Disorders and Injuries.

PMID- 30188252
TI  - Comparison of Er,Cr:YSGG Laser Handpieces for Class II Preparation and
      Microleakage of Silorane- or Methacrylate-Based Composite Restorations.
AB  - OBJECTIVE: The aim of this study was to evaluate the influence of cavity
      preparation with different Er,Cr:YSGG laser handpieces on microleakage of
      different posterior composite restorations. METHODS: Fifty-four extracted intact
      human premolars were randomly assigned to three groups according to cavity
      preparation method: Bur Group: high-speed diamond bur (Diatech), MD Group:
      Er,Cr:YSGG laser Waterlase MD handpiece (Biolase Millennium II), and Turbo Group:
      Er,Cr:YSGG laser Waterlase MD TURBO handpiece (Biolase Millennium II). One
      hundred eight Class II slot cavities were prepared on the mesial and distal
      proximal surfaces of each tooth, and the cavity preparation times required were
      determined. The groups were then subdivided according to the restorative systems
      used (n = 12): a conventional methacrylate-based microhybrid composite (Filtek
      P60+Adper Single Bond 2/3M); a silorane-based resin composite (Filtek
      Silorane+Silorane System Adhesive/3M); and a nanohybrid methacrylate-based
      composite (Kalore+G-Bond/GC). The restorative systems were applied according to
      the manufacturers' recommendations. Following thermocycling (X5000; 5 degrees C
      55 degrees C), the teeth were coated with nail varnish except the restoration
      margins, immersed in 0.5% basic fuchsin dye solution, and sectioned in a
      mesiodistal direction. Dye penetration was evaluated under a light microscope for
      occlusal and cervical margins. Data were analyzed with one-way ANOVA and chi
      square tests (p < 0.05). RESULTS: The cavity preparation time (mean +/- SD)
      required for Bur, MD, and Turbo group was 31.25 +/- 3.82, 222.94 +/- 15.85, and
      92.5 +/- 7.42 sec, respectively, and the differences among the groups were
      statistically significant (p < 0.05). Comparing the occlusal and cervical
      microleakage scores, no statistically significant differences were found among
      the groups and subgroups (p > 0.05). CONCLUSIONS: Er;Cr:YSGG laser cavity
      preparation with the Turbo handpiece needed shorter time than the MD handpiece,
      although it needed longer time than the conventional diamond bur. The use of
      different handpieces of Er,Cr:YSGG laser did not differ from conventional
      preparation with diamond bur in terms of microleakage with the tested
      methacrylate- and silorane-based posterior composite restorative systems.

PMID- 30188254
TI  - Of Acceptance and Celebration.

PMID- 30188253
TI  - Long-Term Effect of Pulsed Nd:YAG Laser in the Treatment of Patients with Rotator
      Cuff Tendinopathy: A Randomized Controlled Trial.
AB  - OBJECTIVE: The purpose of the present study was to investigate the long-term
      effect of pulsed Nd:YAG laser on the treatment of rotator cuff tendinopathy.
      METHODS: Sixty patients with rotator cuff tendinopathy participated and completed
      the study. The mean age was 50.2 +/- 3.6 years. Participants were randomly
      assigned to one of two groups: the control group and the treatment group. Both
      groups were treated with an exercise program, in addition to the pulsed Nd:YAG
      laser received by the treatment group and the "sham" laser received by the
      control group, both for three sessions per week for 4 weeks. Outcome measures
      included pain, assessed by the visual analog scale, and range of motion (ROM),
      assessed using a traditional goniometer, while the shoulder pain and disability
      index were used to evaluate the functional recovery of the shoulder joint.
      Evaluation was carried out before treatment, immediately after treatment, 3
      months posttreatment, and 6 months posttreatment. Statistical analyses were used
      to investigate the effect of interventions and to compare the study groups'
      pretreatment, posttreatment, and at follow-up points. The significance level was
      set to p < 0.05. RESULTS: Pain was significantly decreased after treatment and at
      follow-up points, while ROM and shoulder functions were significantly improved
      after treatment and at follow-up intervals in both groups. The improvement was
      more significant in the treatment group than in the control group posttreatment
      and at follow-up intervals. CONCLUSIONS: Pulsed Nd:YAG laser combined with an
      exercise program seems to be more effective in the treatment of patients with
      rotator cuff tendinopathy than a sham laser with exercises.

PMID- 30188255
TI  - Using Root Cause Analysis and Occupational Safety Research to Prevent Child
      Sexual Abuse in Schools.
AB  - Significant progress has been made in the past two decades understanding how
      child molesters gain access to children and molest them while manipulating others
      to not get caught. However, incidents of child sexual abuse in schools by
      educators, and by other children, continue. This manuscript suggests that a
      comprehensive solution involves two components: (1) using root cause analysis
      methodology to systematically identify and integrate repetitive causes; (2) to
      use the findings from voluminous occupational safety research focusing on low
      frequency but high-intensity events. Additionally, this manuscript describes
      eight organizational operations and practices that may reduce the risk of sexual
      abuse of children by educators or peers in a school setting. These findings were
      based on existing recommendations and on root cause analysis of thousands of
      incidents in schools and other youth serving organizations. Finally, the
      manuscript discusses how a framework drawn from occupational safety research can
      help schools and other youth serving organizations create environments that will
      help to create safe environments. Authors have used both components in working
      with thousands of organizations including faith-based, independent, and urban
      independent school districts, youth development programs, social service
      agencies, camps and so on serving diverse populations in 11 countries.

PMID- 30188256
TI  - Intake of Vitamins and Minerals from Voluntarily Fortified Foods in School
      Children in Central-Eastern Poland.
AB  - OBJECTIVE: To estimate vitamin and mineral intakes from voluntarily fortified
      foods (VFFs) in relation to the Dietary Reference Intake (DRI) in children aged 6
      - 12. METHODS: The study was conducted among 677 school children from Central
      Eastern Poland. Data on VFFs consumption were collected using a semi-quantitative
      food frequency questionnaire containing 58 food items available on the Polish
      market; the content of nutrients in VFFs was estimated using the producers
      labelling declaration. The amounts of nutrients consumed from VFFs were compared
      to DRI and Tolerable Upper Intake Levels (ULs). The distribution of nutrient
      intakes according to the percentage of DRI categories (<20%, 20 - 39.9%, 40 -
      59.9%, 60 - 79.9%, 80 - 99.9%, 100 - 119%, and >120%) was investigated. RESULTS:
      In our study, 78.3% (n = 530) of children were classified as VFF-consumers. The
      most often consumed groups of VFFs were cereal products and juices/non-alcoholic
      beverages (92.5% and 76.6% of children, respectively). The amounts of vitamin D
      intake were negligible (92.5% of children did not exceed 20% of DRI from VFFs);
      vitamins A, E, B12 and calcium were small (>60% did not exceed 40% of DRI);
      vitamins B1, B2, niacin, folic acid, pantothenic acid and iron were moderate
      (>25% consumed 80% of DRI or above); while vitamins C, B6 and biotin were high
      (>40% consumed 100% of DRI or above). Intake above ULs was observed for niacin
      and folic acid (2.6% and 1.1% of children, respectively). CONCLUSIONS:
      Substantial differences between the VFFs contribution of various micronutrients
      to the DRIs were observed. Consumption of VFFs may prevent inadequate intakes for
      the majority of nutrients.

PMID- 30188259
TI  - Factors that may contribute to poor outcome despite good reperfusion after acute
      endovascular stroke therapy.
AB  - Endovascular therapy with mechanical thrombectomy is a formidable treatment for
      severe acute ischemic stroke caused by occlusion of a proximal intracranial
      artery. Its strong beneficial effect is explained by the high rates of very good
      and excellent reperfusion achieved with current endovascular techniques. However,
      there is a sizable proportion of patients who do not experience clinical
      improvement despite successful recanalization of the occluded artery and
      reperfusion of the ischemic territory. Factors such as baseline reserve,
      collateral flow, anesthesia and systemic factors have been identified as
      potential culprits for lack of improvement in the setting of timely and
      successful revascularization. Older age, baseline disability and perhaps
      radiological markers of chronic brain injury can affect the prognosis of patients
      treated with endovascular therapy. Collateral flow is a major determinant of
      outcome after endovascular therapy and it is manifested by the size of the core
      in relation to the volume of the salvageable tissue. Parenchymal and vascular
      imaging can help assess the quality of collateral flow, but the optimal
      radiological strategy for daily practice (i.e. the optimal combination of rapid
      availability and diagnostic precision) has not been established. A sizable body
      of observational evidence indicates that acute hypertension, hyperglycemia and
      fever are associated with worse outcomes after a stroke even after optimal
      reperfusion with endovascular therapy. Lastly, current randomized controlled
      trials in anesthesia for stroke demonstrate similar rates of good functional
      outcome between general anesthesia and conscious sedation suggesting equipoise
      exists.

PMID- 30188257
TI  - Amount of Mononuclear Phagocyte Infiltrate Does Not Predict Area of Experimental
      Choroidal Neovascularization (CNV).
AB  - PURPOSE: Mononuclear phagocytes (MNPs) are present in neovascular age-related
      macular degeneration (nv AMD) which is also called choroidal neovascularization
      (CNV). The number and phenotype of the MNPs depend upon the local environment in
      the CNV and effect of nv AMD therapy. We investigated ocular cell infiltration
      and conditions that modulate angiogenesis in a laser-induced mouse CNV model.
      METHODS: We developed assays to quantify MNPs in our established mouse CNV model.
      One MNP assay quantified the number of subretinal cells peripheral to the CNV
      lesions. A second assay semiquantitatively assesses the number of MNPs localized
      to the CNV lesion. We used these assays to measure the effect of toll-like
      receptor-2 (TLR-2) activation, anti-vascular endothelial growth factor (VEGF)
      therapy, and chemokine (C-C motif) ligand 2 (Ccl2) genetic deletion on MNP
      infiltration after laser injury. RESULTS: Laser injury induced blood vessel
      growth and infiltration of MNPs. Systemic administration of a TLR-2 activating
      peptide increased laser-induced CNV area, MNP cell numbers, and MNP density over
      the CNV lesions. Systemic administration of a VEGF antibody reduced CNV area,
      while Ccl2 genetic deletion increased CNV area. Despite the change in amount of
      angiogenesis, MNP infiltration was, surprisingly, unchanged in these 2
      conditions. CONCLUSIONS: MNP quantification provides biological insights for
      candidate AMD therapies. The number of infiltrating MNP cells does not correlate
      with the amount of laser-induced CNV area.

PMID- 30188258
TI  - Access to digital and social media among Romanian HIV/AIDS clinical providers.
AB  - The WHO/UNAIDS suggests that digital tools - such as social media and online
      training opportunities, can connect providers in difficult social and medical
      contexts to providers elsewhere for guidance, support, and advice. Social media
      is emerging as an innovative option for connecting clinicians together and for
      enhancing access to professional resources. In Romania, characterized by an
      atypical HIV/AIDS epidemic which is further challenged by a range of access
      complexities, it is unclear how often - and which kinds of - social media
      clinicians use to support clinical care. This study was conducted to ascertain
      social media use for clinical providers based in two regions of Romania
      (Transylvania and Moldavia) who face distance challenges that could potentially
      be alleviated by social media interaction. We used an online survey to understand
      what social media are currently popular and perceived to be useful for learning
      clinical information. Descriptive and bivariate analyses were conducted.
      Providers indicated Facebook and WhatsApp were the most common social media
      platforms, with 62% and 45% reporting daily use, respectively. Providers who used
      one media platform were significantly more likely to use another social media
      platform (p < .05). These data are helpful for creating an online training
      platform on HIV/AIDS for Romanian clinical providers.

PMID- 30188260
TI  - Analysis of perchlorate in baby food on Canadian (Ottawa) markets in 2009 and
      estimated dietary exposure.
AB  - In order to determine the baseline levels of perchlorate in major brands of baby
      food, 200 baby food products were collected from retail stores in Ottawa, Canada
      and analysed for perchlorate in 2010. The seven food groups tested were fruit,
      juices, vegetables, meat, yogurt, mixed (vegetable mixed with meat) and other
      (e.g. vegetable mixed with meat and cereal, cheese, egg,). Samples were extracted
      with a mixture of methanol and 1% acetic acid (4:1, v/v). Determination was
      conducted by stable isotope dilution ion chromatography tandem mass spectrometry
      (ID-IC-MS/MS). The complexity of different food matrices required additional
      method validation. The perchlorate levels in 46 samples were found to be lower
      than the quantification limit (0.2 ng g-1). The perchlorate levels in the other
      154 baby food samples were also low; about 96.7% of the baby foods had
      perchlorate levels less than 10 ng g-1 (ranged from 0.2 to 22.4 ng g-1,
      median1.35 ng g-1); only 5 samples had perchlorate levels higher than 10 ng g-1.
      Dietary exposure to perchlorate from analysed baby food was conservatively
      estimated to range from 0.007 to 0.121 ug/kg bw/d based on the mean intake for
      children (1-5 years old).

PMID- 30188273
TI  - Special Section: Highlights of WEFTEC 2017.

PMID- 30188261
TI  - Effect of UV dose on degradation of venlafaxine using UV/H2O2: perspective of
      augmenting UV units in wastewater treatment.
AB  - Many water and wastewater treatment plants (WWTPs) are fitted with a UV system
      that provides post treatment disinfection before the water is released to
      receiving water. This paper presents a study on expected removal for the
      pharmaceutical venlafaxine (VEN) in a typical UV unit at a municipal WWTP with
      analysis of removal rates of an advanced oxidation process using UV irradiation
      with injection of H2O2. The study is supported by bench scale degradation
      experiments on VEN. Results demonstrated that UV can completely degrade VEN, but
      the addition of H2O2 increased pseudo first order rate constant by up to 2.5
      times. Extrapolations of the lab data indicated that removal rates of VEN at the
      UV disinfection unit of a typical municipal WWTP are approximately 0.4% at
      standard operating conditions. With the addition of 10 mg/L of H2O2, degradation
      of VEN can be increased by ten times over existing UV treatment. By studying the
      impact of adjusting parameters such as UV intensity, UV dosage, and H2O2 dosage,
      a framework is set to allow researchers and engineers to move forward with
      developing UV/H2O2 systems that meet their future design needs for pharmaceutical
      removal.

PMID- 30188275
TI  - Bench-Scale Evaluation of Hydrothermal Processing Technology for Conversion of
      Wastewater Solids to Fuels.
AB  - Hydrothermal Liquefaction (HTL) and Catalytic Hydrothermal Gasification (CHG)
      proof-of-concept bench-scale tests were performed to assess the potential of
      hydrothermal treatment for handling municipal wastewater sludge. HTL tests were
      conducted at 300 to 350  degrees C and 20 MPa on three different feeds: primary
      sludge, secondary sludge, and digested solids. Corresponding CHG tests were
      conducted at 350  degrees C and 20 MPa on the HTL aqueous phase output using a
      ruthenium-based catalyst. Biocrude yields ranged from 25 to 37%. Biocrude
      composition and quality were comparable to biocrudes generated from algae feeds.
      Subsequent hydrotreating of biocrude resulted in a product with comparable
      physical and chemical properties to crude oil. CHG product gas methane yields on
      a carbon basis ranged from 47 to 64%. Siloxane concentrations in the CHG product
      gas were below engine limits. The HTL-CHG process resulted in a chemical oxygen
      demand (COD) reduction of > 99.9% and a reduction in residual solids for disposal
      of 94 to 99%.

PMID- 30188274
TI  - Assessment of Selective Withdrawal and Inflow Control on the Hydrodynamics and
      Water Quality of Ilam Reservoir.
AB  - The hydrodynamics and water quality of Ilam reservoir, consisting of three main
      inlet branches and two outlets, was simulated with the CE-QUAL-W2 model. After
      calibrating and verifying the numerical model, effects of various management
      scenarios (selective withdrawal, controlling water inflow, and their
      combinations) were investigated on thermal stratification and water quality. The
      total reduction of nutrient loads derived from the Chaviz and Ema rivers
      decreased the total phosphorus concentration. The chlorophyll a concentration of
      this scenario increased less than in other scenarios. Variation of the withdrawal
      elevation from the surface to the bottom significantly facilitated the heat
      conduction of the water column, therefore, the thermal and dissolved oxygen
      stratification was weakened. The best management scenario was a combination of
      water withdrawal from the bottom and surface and total reduction of nutrient
      loads derived from Chaviz and Ema rivers because of improving eutrophication,
      thermal, and dissolved oxygen stratification in Ilam reservoir.

PMID- 30188276
TI  - CCl4-Enhanced Ultrasonic Irradiation for Ciprofloxacin Degradation and Antibiotic
      Activity.
AB  - In this study, an ultrasound/CCl4 system was used to degrade the
      fluoroquinolone antibiotic, ciprofloxacin, in aqueous solution. The effect of
      CCl4 concentration and initial solution pH on ciprofloxacin degradation were
      investigated. The results showed that ciprofloxacin degraded effectively under an
      ultrasound/CCl4 system, with degradation efficiency increasing from 0.51% to
      50.92%, when the CCl4 concentration ranged from 0.0 to 41.4 mmol/L in 40 min.
      Radical scavenging experiments certified that both *OH and chlorine-containing
      radicals contributed to ciprofloxacin degradation. Eight intermediates were
      detected using ultra high-performance liquid chromatography-mass spectrometry
      (UHPLC-MS) method, including three chloro-intermediates. Based on these results,
      the possible degradation pathways of ciprofloxacin are proposed. Agar diffusion
      tests with E. coli and S. aureus showed that ciprofloxacin's antibacterial
      activity was completely removed in 40 min. This study indicates that an
      ultrasound/CCl4 system can degrade ciprofloxacin and remove its antibacterial
      activity, and thus is a promising process for treating fluoroquinolone
      antibiotics in wastewater.

PMID- 30188277
TI  - Comparison of Microbial Removal Between Slow Dead-End Versus Tangential Sand
      Filtration.
AB  - Both river bank filtration and dead-end sand filtration are becoming
      increasingly applied in rural areas to improve the quality of fecally
      contaminated water. To evaluate the capacity of both treatments to remove E.
      coli, fecal streptococci, and somatic and K13-phages, this study investigates
      their concentrations in diluted wastewater after short-distance tangential sand
      filtration and dead-end sand filtration. Bacteria were almost undetectable in
      both systems after 60 cm depth, and at a pore-water velocity of 1 m/d. Both
      phages underwent removal of 2.5 logs by tangential filtration, whereas dead-end
      filtration removed 5.1 logs and 3.9 logs of K13-phages and somatic phages,
      respectively. After discounting removal by the schmutzdecke, observed only in the
      dead-end filtration, both systems removed phages similarly. It is concluded that
      short-distance river bank filtration, alone, does not meet WHO requirements for
      drinking water. However, the concomitant reduction of suspended solids renders
      the filtered water amenable to further treatment steps.

PMID- 30188278
TI  - Acute Impact of Chlortetracycline on Nitrifying and Denitrifying Processes.
AB  - In the current study, sequential nitrification and anoxic experiments in
      synthetic municipal wastewater were exposed to 0.5 to 100 mg/L of
      chlortetracycline for 24 h to evaluate acute impact on the nitrification, and
      denitrification processes of biological treatment. Both processes were
      significantly (p < 0.05) inhibited at >50 mg/L of chlortetracycline, and the
      results revealed that nitrification was adversely affected by chlortetracycline
      compared with the anoxic process. In nitrification, chemical oxygen removal (COD)
      and ammonia oxidation kinetics were 50% inhibited at 10 mg chlortetracycline/L,
      and nitrite oxidation kinetics at 0.5 mg chlortetracycline/L. Likewise, in the
      anoxic process, 14 and 10 mg/L of chlortetracycline inhibited 50% of COD removal
      and nitrate reduction kinetics, respectively. In nitrification and
      denitrification, 90% of chlortetracycline was removed by adsorbing onto sludge
      suspended solids. In addition, a higher chlortetracycline concentration in anoxic
      effluent, compared with aerobic effluents, indicated a dissimilarity in the
      composition of sludge solids, pH, and biomass production for both processes.

PMID- 30188279
TI  - Free Chlorine Disinfection of Full-Scale MBR Effluent to Achieve 5-Log Virus
      Inactivation.
AB  - A series of full-scale testing was performed at the City of Lathrop
      Consolidated Treatment Facility to determine the "concentration times time" (Ct)
      value for free chlorine disinfection of nitrified membrane bioreactor (MBR)
      effluent to achieve more than 5-log virus inactivation. The full-scale testing
      consisted of tracer study, chlorine decay study, and virus seeding study. The
      virus seeding study was performed at a flow rate of 1 million gal/d (3800
      m3/min), which corresponded to a theoretical contact time of 117 minutes in the
      chlorine contact basin. It was found that Ct values as small as 3 mg.min/L were
      sufficient to achieve 5-log inactivation of MS2 bacteriophage in this study,
      which is comparable to the results of previous bench- and pilot-scale free
      chlorine disinfection studies on nitrified MBR effluent (3 to 40 mg.min/L), as
      well as those of pilot- and full-scale studies on granular media-filtered
      nitrified effluent (2 to 22 mg.min/L).

PMID- 30188280
TI  - Status, Challenges, and Perspectives of Mainstream Nitritation-Anammox for
      Wastewater Treatment.
AB  - The nitritation-anammox process is an efficient and cost-effective approach for
      biological nitrogen removal, but its application in treating mainstream
      wastewater remains a great challenge. Mainstream nitritation-anammox processes
      could create opportunities for achieving energy self-sufficient, or energy
      generating water resource recovery facilities. Significant advancements have been
      achieved via pilot- and full-scale trials to overcome the major obstacles under
      mainstream conditions, such as repression of nitrite-oxidizing bacteria, limiting
      the overgrowth of denitrifiers, and effective selection and retention of ammonia
      oxidizing bacteria and anammox bacteria. This review paper intends to provide a
      detailed update of research progress on mainstream nitritation-anammox processes,
      discuss metabolic interactions, and examine major challenges and possible
      solutions towards the future development.

PMID- 30188281
TI  - CO2 Bubbling to Improve Algal Growth, Nutrient Removal, and Membrane Performance
      in an Algal Membrane Bioreactor.
AB  - Algae generally prefer CO2 through passive gas diffusion to HCO-3 or CO2-3, as
      uptake of carbonate species relies on active transport. In this study, the
      effects of CO2 bubbling on algal growth, nutrient uptake, lipid accumulation, and
      membrane fouling control were investigated in an algal membrane bioreactor (A
      MBR). Bubbling with 10% CO2 in the A-MBR system increased algal specific oxygen
      production rate by 43 +/- 5% and algal productivity by 39 +/- 1%, even though
      there was abundant dissolved inorganic carbon available in the secondary
      wastewater effluent (about 3.6 mM). Meanwhile, nitrogen removal capacity
      increased from originally 2.6 +/- 0.4 g/m3*d to 3.6 +/- 0.4 g/m3*d through
      continuous CO2 bubbling. Furthermore, membrane fouling was significantly reduced
      in the A-MBR system with CO2 addition, likely because of reduced mineral
      precipitation on the membrane at lower pHs.

PMID- 30188283
TI  - Renaissance of an Old Topic: From Borazines to BN-doped Nanographenes.
AB  - Graphene is one of the leading materials in today's science, but the lack of a
      band gap limits its application to replace semiconductors in optoelectronic
      devices. To overcome this limitation, the replacement of C=C bonds by
      isostructural and isoelectronic bonds is emerging as an effective strategy to
      open a band gap in monoatomic graphene layers. First prepared by Stock and
      Pohland in 1926, borazine is the isoelectronic and isostructural inorganic
      analogue of benzene, where the C=C bonds are replaced by B-N couples. The strong
      polarity of the BN bonds widens the molecular HOMO-LUMO gap, imparting strong UV
      emission/absorption and electrical insulating properties. These properties make
      borazine a valuable molecular scaffold to be inserted as doping units in
      graphitic-based carbon materials to tailor a relevant band gap. It is with this
      objective that we became interested in the development of new synthetic organic
      methodologies to gain access to functionalized borazine derivatives. In
      particular, we have described the synthesis of borazine derivatives that,
      featuring aryl substituents at the B-centers bearing ortho-functionalities, are
      exceptionally stable against hydrolysis. Building on these structural motifs, we
      prepared hybrid BN-doped polyphenylene nanostructures featuring controlled doping
      patterns, both as dosage and orientation. Finally, exploiting the Friedel-Craft
      electrophilic aromatic substitution, we could develop the first rational
      synthesis of the first soluble hexa-peri-hexabenzoborazinocoronene and measured
      its optoelectronic properties, showing a widening of its gap compared to its full
      carbon congener.

PMID- 30188284
TI  - Oxidation of N,N-Disubstituted Hydroxylamines to Nitrones: The Search for More
      Sustainable Selective and Practical Stoichiometric Oxidants.
AB  - Nitrones are key intermediates for the total synthesis of nitrogen-containing
      natural products and analogues. The direct oxidation of the corresponding N,N
      disubstituted hydroxylamines is one of the most straightforward methods to access
      such compounds. In this account, we describe the state of the art of this
      oxidative transformation using stoichiometric reagents. We will focus on the
      efforts made in the last 25 years to oxidize polyhydroxylated cyclic
      hydroxylamines, due to our long-standing interest in the total synthesis of
      alkaloids and other glycomimetics. Particular attention will be devoted to the
      discussion of the regioselectivity issue arising when unsymmetrical and highly
      functionalized substrates are involved.

PMID- 30188282
TI  - Assessing the Effects of RAS Fermentation on EBPR Performance and Associated
      Microbial Ecology.
AB  - Enhanced biological phosphorus removal (EBPR) is an engineered water resource
      recovery facility (WRRF) process configuration that can produce effluent P < 0.5
      mg/L. To consistently achieve low effluent P concentrations, EBPR requires
      volatile fatty acids (VFAs) to induce requisite biochemical reactions. Moreover,
      returned activated sludge (RAS) nitrate concentrations must be minimized.
      Returned activated sludge fermentation can potentially address process needs.
      However, research detailed herein highlights concerns with RAS fermentation
      integrated with EBPR. Under 2 and 4 hours of RAS fermentation periods, no
      consequential VFA production was observed; similar results were observed in batch
      tests with RAS from a full-scale EBPR WRRF. More critically, EBPR performance was
      poor, with average effluent concentrations of 1.0 to 2.4 mg/L. Furthermore, the
      glycogen accumulating organism (GAO) fraction under RAS fermentation was 4.3 to
      8.7 times higher than in a conventional EBPR mixed microbial consortium (MMC).
      Integrated RAS fermentation-EBPR only performed well under "high" RAS nitrate;
      thus, should RAS fermentation be implemented, careful control to prevent
      anaerobic conditions in the fermentation zone is required.

PMID- 30188285
TI  - Stereoselective Reactions with Chiral Schiff Base Metal Complexes.
AB  - Chiral Schiff bases are privileged chiral ligands, capable of transmitting chiral
      information in many stereoselective processes. Their modular nature, the
      possibility to modify their electronic character, and their ability to coordinate
      many metals, gives these chiral ligands broad utility and these have been
      investigated by many research groups around the world. For more than 20 years our
      research group has devoted attention to the application of chiral Schiff bases in
      the development of new stereoselective processes and in this brief survey we
      present our principal results and achievements in this field.

PMID- 30188286
TI  - Chemical Functionalization of Carbon Nanomaterials: Bridging the Gap between
      Simple Carriers and Smart (Metal-free) Catalysts.
AB  - The last few years have witnessed a wonderful technological renaissance that
      boosted the development of carbon-based nanomaterials (CNMs) doped with light
      heteroelements and featuring hierarchical porous architectures as valuable metal
      free catalysts for a number of key industrial transformations. To date, several
      approaches to their synthesis have been developed, although many of them lack any
      real control of the final doping and composition. In contrast, chemical
      functionalization offers a unique and powerful tool to tailor CNMs' chemical and
      electronic surface properties as a function of their downstream application in
      catalysis. Different catalytic processes
      (hydrolysis/esterification/transesterification reactions, C-C bond forming
      reactions, CO2 derivatization into products of added value and electrochemical
      oxygen reduction reactions (ORR)) can be conveniently promoted by these
      materials. In addition, selected examples from this series offer a valuable
      platform for the in-depth comprehension of the underlying reaction mechanisms.
      This perspective article offers an overview on the main examples of ad hoc
      chemically decorated CNMs successfully exploited as metal-free catalysts,
      highlighting at the same time the importance of the surface chemistry control for
      the design of more active, metal-free and single-phase heterogeneous catalysts.

PMID- 30188287
TI  - Arene Ruthenium(II) Complexes with Phosphorous Ligands as Possible Anticancer
      Agents.
AB  - Ruthenium(II) complexes of formula [Ru(eta6-arene)Cl2 (PTA)] (RAPTA) are
      potential anticancer drugs with notable antimetastatic and antiangiogenic
      activity, which are now pointing to clinical trials. Following the great interest
      aroused by these compounds, a variety of RAPTA derivatives, obtained by chloride
      substitution and/or containing functionalized arene ligands, and complexes
      resembling the RAPTA structure but bearing different phosphorous ligands have
      been synthesized and evaluated for their anticancer activity. An overview of all
      of these biologically relevant complexes will be given, with particular reference
      to the anticancer behaviour exhibited by the compounds and the possible
      relationship with structural aspects.

PMID- 30188288
TI  - Enantioselective Reductions Promoted by (Cyclopentadienone)iron Complexes.
AB  - (Cyclopentadienone)iron complexes have recently gained widespread interest as
      cheap metal-based pre-catalysts for the reduction of carbonyl compounds and
      imines, thanks to their air- and moisture-stability and easy
      synthesis/purification. In this account, several approaches are presented to
      achieve enantioselective C=O and C=N bond reduction using this class of iron
      complexes. Most of the examples, used in the asymmetric reduction of ketones,
      rely on chiral (cyclopentadienone)iron complexes, featuring a chiral
      cyclopentadienone backbone and/or a chiral monophosphoramidite ligand, introduced
      by replacement of a CO ligand. The enantiomeric excesses achieved so far with
      this strategy are at best moderate. Better ees could be obtained with an
      alternative approach, used in the enantioselective reduction of C=N bonds, which
      consists in combining an achiral (hydroxycyclopentadienyl)iron complex (i.e. the
      activated form of a (cyclopentadienone)iron complex) with a chiral phosphoric
      acid.

PMID- 30188289
TI  - The Stille Reaction: Applications in the Synthesis of Organic Dyes for DSSCs.
AB  - The cross-coupling reaction of organic electrophiles with organostannanes,
      traditionally known as the Stille reaction, has found renewed interest in the
      preparation of new organic materials such as conjugated polymers, organic
      semiconductors and photoactive molecules for use in organic photovoltaics.
      Moreover, a very recent field in which the Stille reaction has found successful
      application is that of the design and synthesis of new photosensitizers for dye
      sensitized solar cells (DSSCs). DSSCs are considered a promising alternative for
      energy production from renewable sources. In such devices light harvesting is
      carried out by a dye which is generally a highly conjugated molecule. Due to the
      mild operating conditions and the high functional-group compatibility, the Stille
      reaction proved to be a powerful tool not only for the preparation of
      photosensitizers, but also to plan their chemical elaboration in order to tune
      and optimize their photophysical, electrochemical and photovoltaic properties. In
      this microreview some recent examples of the Stille reaction in the synthesis of
      organic dyes for DSSC are reported.

PMID- 30188291
TI  - Catalytic Arene-forming Aldol Condensation: Stereoselective Synthesis of
      Rotationally Restricted Aromatic Compounds.
AB  - By taking inspiration from the fascinating biosynthetic machinery that creates
      aromatic polyketides, our group investigates analogous reactions catalyzed by
      small molecules. We are particularly captivated by the prospects of
      intramolecular aldol condensation reactions to generate different rotationally
      restricted aromatic compounds. In a first project of our independent research
      group, a highly stereoselective amine catalyzed synthesis of axially chiral
      biaryls, tertiary aromatic amides and oligo-1,2-naphthylenes has been developed.
      In this article, we outline the twists and turns for our escape from the aromatic
      flatland to structurally intriguing chiral arene scaffolds relevant for various
      fields of application.

PMID- 30188290
TI  - Organic Diselenides: Versatile Reagents, Precursors, and Intriguing Biologically
      Active Compounds.
AB  - In this account, we describe how some organic diselenides were successfully used
      in the past as reagents for asymmetric stereoselective synthesis and more
      recently as precursors of catalysts and reagents applied in new green protocols.
      A biomimetic approach offered the possibility to perform oxidative reactions
      using hydrogen peroxide as oxidant and water as medium affording the desired
      products in excellent yields under mild conditions. The umpolung of the selenium
      atom gave novel nucleophilic reagents having a strongly accelerated reaction rate
      in on water conditions. Finally, the use of diselenides to exploit specific
      biological activities is described here as seminal examples of a promising field
      of research currently under investigation in our group.

PMID- 30188293
TI  - Quantification of Quaternary Ammonium Compounds Against Surrogate Matrix by HILIC
      MS/MS.

PMID- 30188295
TI  - Producing Renewable Energies - Swiss Innovation at EXPO 2017 in Astana.

PMID- 30188294
TI  - Advanced Cell Culture Systems: Exactly what Academia and Industry Need!

PMID- 30188297
TI  - 10th Young Faculty Meeting, 6th June 2017.

PMID- 30188299
TI  - Editorial.

PMID- 30188300
TI  - Forces Shaping the Conditions of Our Lives.

PMID- 30188296
TI  - SCHeMA EU Project Summer School Report (Bilbao June 16 - 17, 2016).
AB  - This conference report describes the training activities that took place in the
      frame of the Integrated in Situ Chemical MApping probe (SCHeMA) summer school
      organized from the 14th to the 16th of June 2016 in Bilbao (Spain).

PMID- 30188301
TI  - Strategies to Address Individual Level Social Determinants of Health Designed to
      Cultivate the Next Generation of Minority Nurse Leaders Committed to Health
      Equity.
AB  - In response to the need for increased racial and ethnic diversity in the nursing
      profession, the Duke University School of Nursing (DUSON) established the Academy
      for Academic and Social Enrichment for Leadership Development in Health Equity
      (Health Equity Academy). The aim of the Health Equity Academy is to improve the
      diversity of the nursing workforce by expanding nursing education opportunities
      for underrepresented minority (URM) students who are economically disadvantaged
      to prepare for, enroll in, and graduate from the DUSON's Accelerated Bachelors of
      Science in Nursing program. The goal of this program is to cultivate URM nursing
      graduates with advanced knowledge and leadership skills who can address health
      disparities and positively influence health care issues currently plaguing
      underrepresented populations. The article discusses the Health Equity Academy
      framework, which consists of two unique components: the Pre-entry Immersion in
      Nursing and the Pathway to Success in Nursing (PSN). These two components are
      designed to address the nursing student individual level social determinants
      which could be potential barriers to success as well as provide support in their
      academic and professional development goals.

PMID- 30188302
TI  - Potential Therapeutic Benefits of Babywearing.
AB  - Babywearing is defined as the act or practice of keeping an infant close to an
      adult's torso by using a supporting device that straps to the front of the
      adult's body (Merriam-Webster, n.d.). The practice of babywearing as an adjunct
      to therapy is likely to be beneficial to children and caregivers. Although
      research on babywearing is limited, the therapeutic benefits of "skin-to-skin
      care" or "kangaroo care" have been empirically established. Building on this
      research, this article attempts to raise awareness about babywearing by
      elucidating the likely therapeutic benefits for children with disabilities or
      special needs and areas for future research.

PMID- 30188303
TI  - Seeking Divine Solutions for Our Youth: A Conversation With Imam Hassan Mohamud.
AB  - The life period of youth and young adulthood is a time of forming identities and
      making allegiances. In the absence of adequate, consistent support, negative
      influences abound. Religious and spiritual leaders are potential sources of
      support for young people. Increasingly, empirical reports document the influence,
      most of it positive, of religion on both physical and emotional well-being. This
      interview with a Somali religious leader illustrates the importance of
      understanding and addressing the unique needs and challenges of young Somalis in
      Minnesota and beyond.

PMID- 30188304
TI  - Carbohydrate Counting in the Acute Care Setting: Development of an Educational
      Program Based on Cognitive Load Theory.
AB  - The care of noncritically ill hospitalized patients with diabetes mellitus
      requiring insulin administration is multidisciplinary and complex. Evidence
      indicates that staff nurses may benefit from additional training in the
      nutritional management of patients with diabetes. In addition, unlicensed
      assistive personnel may be involved in the feeding and point-of-care testing of
      diabetic patients and thus play an important role in nursing care of such
      patients. Cognitive load theory assists educators in the identification of
      specific cognitive challenges that learners may face when presented with new
      material, but it also presents solutions to such challenges by way of specific
      instructional design methods to help overcome them. An educational program was
      piloted on a mixed audience of registered nurses and unlicensed assistive
      personnel at a community hospital; satisfaction with the program was found to be
      high.

PMID- 30188305
TI  - Neonatal Abstinence Syndrome: The Experience of Infant Massage.
AB  - Babies born to women who have used opioids during pregnancy frequently develop
      withdrawal symptoms following birth. Although a consistently used protocol is not
      available to treat these infants, interventions commonly used include a
      pharmacological regimen and supportive care such as swaddling, frequent feedings,
      decreased sensory stimulation, and protection from skin breakdown (Murphy
      Oikonen, Montelpare, Bertoldo, Southon, & Persichino, 2012). A qualitative study
      was designed to better understand how infant massage might impact these babies'
      behavior and the mothers' relationship with their babies. Themes derived from the
      data include empowerment, enjoyment and bonding, and calm and comfort. The themes
      suggest that infant massage helps alleviate withdrawal symptoms in infants while
      fostering a connection between mother and child.

PMID- 30188306
TI  - Parental Consent for Adolescent Research.
AB  - The purpose of this article is to increase understanding about how to obtain
      institutional review board approval to waive parental consent for adolescent
      research that involves minimal risk to subjects and/or that cannot be carried out
      practicably without the waiver. Because of IRB guidelines, the researchers were
      unable to use passive parental consent for a study of adolescent nonmedical
      prescription drug use (NMPDU). Without knowledge of waiver 45 C.F.R. S46.116 of
      the U.S. Department of Health and Human Services Code of Federal Regulations
      regarding the protection of human research subjects, the study design required
      active parental consent for survey administration. This requirement limited study
      participation and increased costs. Using the waiver, the study design could have
      waived parental consent with adolescent assent. By increasing awareness of the 45
      C.F.R. S46.116 waiver and its subparts, the researchers hope to inform future
      researchers about reducing barriers to future adolescent research. Lessons
      learned include how using the waiver may decrease research costs, reduce
      participant selection bias, increase participant response rate, and expand data
      available to contribute to critical, emerging adolescent health issues such as
      NMPDU.

PMID- 30188307
TI  - Home Care Moments.
AB  - This article offers reflections from a pediatric nurse on the unique nature of
      home care. The purpose of the writing was to process the experience of being a
      brand new nurse in a home care setting.

PMID- 30188309
TI  - Research Abstracts Integrated Care.

PMID- 30188308
TI  - Reaching Millennials With Nursing History.
AB  - The North Carolina Nursing History (NCNH) website, a comprehensive, award
      winning, and rich educational resource, was developed by nursing and library
      faculty and staff at Appalachian State University and is being used by nursing
      faculty and students. Most of today's students prefer to learn with online tools.
      The advantages of using a digital nursing history website include access to an
      abundance and diversity of historical content in a student-friendly format.

PMID- 30188310
TI  - A person-centred Approach to holistic Assessment.
AB  - Holistic assessment is an important aspect of providing high quality care focused
      on meeting a patient's individual needs. A holistic assessment should take into
      consideration the overall health of the patient, including their physical,
      psychological, social and spiritual wellbeing. This paper aims to clarify the
      meaning of 'holistic' in relation to dentistry and describes how this relates to
      treating the person as a whole, rather than be aligned to any particular
      treatment philosophy. The importance of a person-centred approach in undertaking
      a holistic assessment is highlighted. A brief overview of the relational aspects
      of person-centred care (PCC) is provided and it is suggested that four key
      dimensions of PCC should be considered as important factors in holistic
      assessment: connection, caring attitude, communication and control.

PMID- 30188311
TI  - The Role of the Dental Team in the Prevention of Systemic Disease: the Importance
      of Considering Oral Health As Part of Overall Health.
AB  - The global burden of non-communicable disease (NCD) is significant and the World
      Health Organization highlighted tackling non-communicable diseases (NCDs) as a
      key strategic objective in their 'Global action plan for the prevention and
      control of noncommunicable diseases, 2013-2020'. Dental teams see a large
      proportion of the UK population at regular intervals, including when patients
      deem themselves to be in good dental health. Given that many NCDs have shared
      risk factors, often behavioural with implications for oral and general health,
      dental teams are ideally placed to provide preventative advice for diseases
      beyond the oral environment. This article aims to assess the key risk factors for
      NCDs and oral diseases as well as assess the potential for dental care
      professionals (DCPs) to provide patients with general health advice based on
      their individual risk factors.

PMID- 30188312
TI  - Making Every Contact in Dentistry Count.

PMID- 30188313
TI  - Patients with Psychiatric Disorders: What the General Dental Practitioner Needs
      to Know.
AB  - Psychiatric illness is extremely common and the general dental practitioner (GDP)
      will inevitably encounter patients with such an illness. This article outlines
      common psychiatric conditions that the GDP should be familiar with alongside its
      impact on oral health. It also gives a systematic approach to dealing with a
      patient who presents to practice with an undiagnosed psychiatric illness, whereby
      the illness interferes with delivery of suitable dental care.

PMID- 30188314
TI  - Spotting and Tackling Poor Mental Health in Colleagues and Patients.

PMID- 30188315
TI  - Regonising Ear, Nose and Throat Conditions in the Dentist's Chair.
AB  - The dentist's chair presents an opportunity to pick up ear nose and throat
      lesions, by virtue of the close proximity of the anatomical areas. Urgent two
      week wait referral can expedite assessment and management of head and neck
      malignancies, thereby improving the prognosis. In this paper, we attempt to
      highlight the ear, nose and throat (ENT) conditions that need a two week
      referral, as well as the benign head and neck lesions which can potentially be
      picked up in a dentist's chair.

PMID- 30188316
TI  - Assessment of Neck Lumps in Relation to Dentistry.
AB  - Neck lumps have a varied aetiology, from a benign inflammatory cause to the first
      presenting sign of a malignancy. Patients may present to primary care complaining
      of a neck lump or they may be identified as an incidental finding during routine
      examination. This article highlights a structured approach to the initial
      assessment including history taking, risk factor assessment and clinical
      examination. Further investigations undertaken in a secondary care setting, such
      as ultrasound and guided fine needle aspirations, are then discussed. The common
      congenital, inflammatory, infective, vascular and neoplastic causes of neck lumps
      and their management and specialist referral pathway are discussed.

PMID- 30188317
TI  - Assessment and Management of Lumps on the Face: a Guide for the General Dental
      Practitioner.
AB  - There are a number of conditions that can present as a lump on the face. The
      general dental practitioner is uniquely trained in head and neck anatomy and
      pathology and should be able to identify these important conditions and consider
      appropriate investigations. Understanding what requires urgent specialist
      assessment and what can be referred routinely can be difficult, but is crucial to
      high quality patient outcomes. This article aims to simplify common conditions
      that may present as a lump on the face or be an incidental finding within the
      primary dental care setting. It is by no means an exhaustive description of all
      the pathology that may be encountered within this anatomical region, however it
      should form a useful and practical framework for common presentations.

PMID- 30188318
TI  - Tattoos of the Head, Neck and Hands.
AB  - Tattooing is ancient and gaining popularity in present day society. While many
      tattoos are decorative body art, certain tattoos of the head, neck and hands may
      provide helpful insights into, among other traits, the personality, beliefs or
      orientation of an individual.

PMID- 30188319
TI  - The Way Forward for Dental Leadership.

PMID- 30188320
TI  - Receptive field center-surround interactions mediate context-dependent spatial
      contrast encoding in the retina.
AB  - Antagonistic receptive field surrounds are a near-universal property of early
      sensory processing. A key assumption in many models for retinal ganglion cell
      encoding is that receptive field surrounds are added only to the fully formed
      center signal. But anatomical and functional observations indicate that surrounds
      are added before the summation of signals across receptive field subunits that
      creates the center. Here, we show that this receptive field architecture has an
      important consequence for spatial contrast encoding in the macaque monkey retina:
      the surround can control sensitivity to fine spatial structure by changing the
      way the center integrates visual information over space. The impact of the
      surround is particularly prominent when center and surround signals are
      correlated, as they are in natural stimuli. This effect of the surround differs
      substantially from classic center-surround models and raises the possibility that
      the surround plays unappreciated roles in shaping ganglion cell sensitivity to
      natural inputs.

PMID- 30188323
TI  - Surface polarons and optical micro-cavity modulated broad range multi-mode
      emission of Te-doped CdS nanowires.
AB  - The optical confinement and strong carrier coupling within a semiconductor
      nanostructure cavity are crucial for the modulation of emission properties.
      Fundamental understanding of the light-matter interaction in a low dimensional
      system is important. In this paper, we synthesized high-quality hexagonal Te
      doped CdS nanowires by two-step chemical vapor deposition and investigated
      systematically the doping concentration, temperature, excitation power,
      excitation wavelength dependent Raman, photoluminescence and carrier lifetime
      decay. Scanning electron microscopy, energy dispersive x-ray spectrometry and x
      ray diffraction confirmed Te-doping in the as-prepared samples. The strong
      surface optical (SO) phonon mode is observed in the micro-Raman spectra of an
      individual Te-CdS nanowire, which is unsuitable in large-sized structures. In
      situ micro-photoluminescence (MU-PL) characterization shows dominant confined
      defect state emission with whispering gallery mode (WGM) characteristics. The
      emission peak position shifts under increased excitation power, demonstrating the
      inelastic scattering by bound carriers. In addition, the short wavelength
      emission modes are dominant at a low temperature (80 K) while the long wavelength
      emission modes are dominant at a high temperature (300 K) due to different
      recombination processes contributing to the WGM resonant bands, which was also
      confirmed by the time-resolved PL measurement. All these results reflect strong
      coupling between the surface evanescent-wave in the WGM cavity and the SO
      phonon/polaron, which will facilitate the rational tailoring of surface/interface
      relevant properties for nanophotonic device applications.

PMID- 30188321
TI  - Enhanced ER proteostasis and temperature differentially impact the mutational
      tolerance of influenza hemagglutinin.
AB  - We systematically and quantitatively evaluate whether endoplasmic reticulum (ER)
      proteostasis factors impact the mutational tolerance of secretory pathway
      proteins. We focus on influenza hemaggluttinin (HA), a viral membrane protein
      that folds in the host's ER via a complex pathway. By integrating chemical
      methods to modulate ER proteostasis with deep mutational scanning to assess
      mutational tolerance, we discover that upregulation of ER proteostasis factors
      broadly enhances HA mutational tolerance across diverse structural elements.
      Remarkably, this proteostasis network-enhanced mutational tolerance occurs at the
      same sites where mutational tolerance is most reduced by propagation at fever
      like temperature. These findings have important implications for influenza
      evolution, because influenza immune escape is contingent on HA possessing
      sufficient mutational tolerance to evade antibodies while maintaining the
      capacity to fold and function. More broadly, this work provides the first
      experimental evidence that ER proteostasis mechanisms define the mutational
      tolerance and, therefore, the evolution of secretory pathway proteins.

PMID- 30188324
TI  - 3D bioprinting of a hyaluronan bioink through enzymatic-and visible light
      crosslinking.
AB  - Extrusion-based three-dimensional bioprinting relies on bioinks engineered to
      combine viscoelastic properties for extrusion and shape retention, and biological
      properties for cytocompatibility and tissue regeneration. To satisfy these
      conflicting requirements, bioinks often utilize either complex mixtures or
      complex modifications of biopolymers. In this paper we introduce and characterize
      a bioink exploiting a dual crosslinking mechanism, where an enzymatic reaction
      forms a soft gel suitable for cell encapsulation and extrusion, while a visible
      light photo-crosslinking allows shape retention of the printed construct. The
      influence of cell density and cell type on the rheological and printability
      properties was assessed correlating the printing outcomes with the damping
      factor, a rheological characteristic independent of the printing system. Stem
      cells, chondrocytes and fibroblasts were encapsulated, and their viability was
      assessed up to 14 days with live/dead, alamar blue and trypan blue assays.
      Additionally, the impact of the printing parameters on cell viability was
      investigated. Owing to its straightforward preparation, low modification,
      presence of two independent crosslinking mechanisms for tuning shear-thinning
      independently of the final shape fixation, the use of visible green instead of UV
      light, the possibility of encapsulating and sustaining the viability of different
      cell types, the hyaluronan bioink here presented is a valid biofabrication tool
      for producing 3D printed tissue-engineered constructs.

PMID- 30188325
TI  - Two-dimensional plumbum-doped tin diselenide monolayer transistor with high
      on/off ratio.
AB  - Doping can effectively regulate the electrical and optical properties of two
      dimensional semiconductors. Here, we present high-quality Pb-doped SnSe2
      monolayer exfoliated using a micromechanical cleavage method. X-ray photoelectron
      spectroscopy measurement demonstrates that Pb content of the doped sample is
      ~3.6% and doping induces the downward shift of the Fermi level with respect to
      the pure SnSe2. Transmission electron microscopy characterization exhibits that
      Pb0.036Sn0.964Se2 nanosheets have a high-quality hexagonal symmetry structure and
      Pb element is uniformly distributed in the nanosheets. The current of the SnSe2
      field effect transistors (FETs) was found to be very difficult to turn off due to
      the high electron density. The FETs based on the Pb0.036Sn0.964Se2 monolayer show
      n-type behavior with a high on/off ratio of 106 which is higher than any values
      of SnSe2 FETs reported at the moment. The estimated carrier concentration of
      Pb0.036Sn0.964Se2 is approximately six times lower than that of SnSe2. The
      results suggest that the method of reducing carrier concentration by doping to
      achieve high on/off ratio is effective, and Pb-doped SnSe2 monolayer has
      significant potential in future nanoelectronic and optoelectronic applications.

PMID- 30188328
TI  - Commentary on Making a Case for the Use of Platelet-Rich Plasma in Cicatricial
      Alopecia.

PMID- 30188327
TI  - Update: Botulinum Toxin for Depression: More Than Skin Deep.

PMID- 30188326
TI  - Deletion of Tmtc4 activates the unfolded protein response and causes postnatal
      hearing loss.
AB  - Hearing loss is a significant public health concern, affecting over 250 million
      people worldwide. Both genetic and environmental etiologies are linked to hearing
      loss, but in many cases the underlying cellular pathophysiology is not well
      understood, highlighting the importance of further discovery. We found that
      inactivation of the gene Tmtc4 (transmembrane and tetratricopeptide repeat 4),
      which was broadly expressed in the mouse cochlea, caused acquired hearing loss in
      mice. Our data showed Tmtc4 enriched in the endoplasmic reticulum, and that it
      functioned by regulating Ca2+ dynamics and the unfolded protein response (UPR).
      Given this genetic linkage of the UPR to hearing loss, we demonstrated a direct
      link between the more common noise-induced hearing loss (NIHL) and the UPR. These
      experiments suggested a novel approach to treatment. We demonstrated that the
      small-molecule UPR and stress response modulator ISRIB (integrated stress
      response inhibitor), which activates eIF2B, prevented NIHL in a mouse model.
      Moreover, in an inverse genetic complementation approach, we demonstrated that
      mice with homozygous inactivation of both Tmtc4 and Chop had less hearing loss
      than knockout of Tmtc4 alone. This study implicated a novel mechanism for hearing
      impairment, highlighting a potential treatment approach for a broad range of
      human hearing loss disorders.

PMID- 30188329
TI  - Laser Ablation of the Recipient Area With Platelet-Rich Plasma-Enriched Epidermal
      Suspension Transplant in Vitiligo Surgery: A Pilot Study.
AB  - BACKGROUND: Noncultured epidermal cell suspension transplantation is a very
      popular surgical modality for treating vitiligo. However, the procedure can be
      modified to improve results. OBJECTIVE: To study the extent of repigmentation
      with noncultured trypsinized fragmented epidermal suspension using platelet-rich
      plasma (PRP) as a suspending agent and pixel erbium yttrium aluminium garnet
      laser for ablation of recipient area in patients with stable vitiligo. MATERIALS
      AND METHODS: Autologous noncultured tiny epidermal fragments suspended in PRP
      were grafted on superficially pixel erbium YAG laser-ablated vitiligo lesions in
      10 patients. The repigmentation was evaluated over a period of 6 months using a
      digital image analysis system. RESULTS: Repigmentation was observed as early as 2
      weeks after the treatment. Of 20 lesions, 12 (60%) showed excellent response; of
      which 10 lesions (50%) showed complete repigmentation in 8 weeks only. There were
      no milia or keloid formation, donor-site scarring, stuck on appearance at
      recipient site or infection. CONCLUSION: This study indicates that PRP-enriched
      epidermal suspension transplant (LA-PEEST) has the potential to improve the rate
      of healing and repigmentation in vitiligo patches. Further investigations and
      larger controlled trials are required to establish this technique as a rapid
      surgical method to restore pigmentation.

PMID- 30188330
TI  - Do current treatment options fall short for persistent vasomotor symptom bother
      in women over 60?

PMID- 30188331
TI  - Inter-relationship between diet, lifestyle habits, gut microflora, and the equol
      producer phenotype: baseline findings from a placebo-controlled intervention
      trial.
AB  - OBJECTIVE: Equol is an active metabolite of isoflavones produced by gut
      microbiota. It is beneficial to health; however, equol-producing ability varies
      greatly among individuals. These variations depend on the host's gut microbiota
      and lifestyle habits including diet. We investigated the relationship between the
      gut microbiota, lifestyle habits including diet, and equol-producing ability in
      postmenopausal Japanese women. METHODS: We studied 58 postmenopausal Japanese
      women aged 48 to 69 years who visited the Sendai Medical Center in January, 2018.
      Self-administered questionnaires assessed their recent and remote food intake
      histories and lifestyle habits. Fecal microbiome analysis was performed using a
      next-generation sequencer. Urinary equol was measured using an
      immunochromatographic strip test. Women with urinary equol concentration >1.0 MUM
      were defined as equol producers. RESULTS: Equol-producing bacteria were
      identified in 97% (56) of women; however, only 13 (22%) were equol producers.
      Equol producers showed significantly higher microflora diversity (P = 0.002), and
      significantly different recent and remote food intake patterns compared with
      equol nonproducers. Higher consumption of foods such as meat, fish, soy,
      vegetables, and Japanese snacks positively affected microbial diversity and equol
      production, whereas a high intake of Ramen and smoking showed negative effects.
      CONCLUSION: Equol production might not depend on the quantity, but on the quality
      of equol-producing bacteria. High microbial diversity might enhance equol
      production. Increasing microbial diversity through healthy lifestyle habits and
      habitual consumption of a wide variety of foods might be useful to maintain a
      healthy gut environment for equol production.

PMID- 30188332
TI  - Tissue biomarkers in nonmuscle-invasive bladder cancer: any role in clinical
      practice?
AB  - PURPOSE OF REVIEW: To summarize recent findings on tissue biomarkers for
      nonmuscle-invasive bladder cancer (NMIBC) with an emphasis on their prognostic
      and predictive role. RECENT FINDINGS: Accurate risk stratification is essential
      and the major driver in patient counseling regarding surveillance and decision
      making relative to therapeutic strategies. In NMIBC, there is an unmet need for
      improving the accuracy of current prognostic and predictive models, which rely
      only on clinicopathologic features and do not reflect the biological
      heterogeneity of the cancer in each individual. Studies continuously shed novel
      light on some processes involved in cancerogenesis, host response and
      interactions in the tumor's own microenvironment, which may be considered as
      potential biomarkers and targets for future directed therapies. SUMMARY:
      Biomarkers are necessary to transform bladder cancer management and usher in the
      age of personalized medicine. The clinical use is, however, still limited because
      of heterogeneity in study design, staining methods and an overall lacking
      adherence to a structured biomarker testing process.

PMID- 30188322
TI  - Transcriptional and epigenomic landscapes of CNS and non-CNS vascular endothelial
      cells.
AB  - Vascular endothelial cell (EC) function depends on appropriate organ-specific
      molecular and cellular specializations. To explore genomic mechanisms that
      control this specialization, we have analyzed and compared the transcriptome,
      accessible chromatin, and DNA methylome landscapes from mouse brain, liver, lung,
      and kidney ECs. Analysis of transcription factor (TF) gene expression and TF
      motifs at candidate cis-regulatory elements reveals both shared and organ
      specific EC regulatory networks. In the embryo, only those ECs that are adjacent
      to or within the central nervous system (CNS) exhibit canonical Wnt signaling,
      which correlates precisely with blood-brain barrier (BBB) differentiation and
      Zic3 expression. In the early postnatal brain, single-cell RNA-seq of purified
      ECs reveals (1) close relationships between veins and mitotic cells and between
      arteries and tip cells, (2) a division of capillary ECs into vein-like and artery
      like classes, and (3) new endothelial subtype markers, including new validated
      tip cell markers.

PMID- 30188333
TI  - Integration of PSMA-targeted PET imaging into the armamentarium for detecting
      clinically significant prostate cancer.
AB  - PURPOSE OF REVIEW: To explore the current state of using prostate-specific
      membrane antigen (PSMA)-targeted PET imaging to aid in the diagnosis of
      clinically significant prostate cancer. RECENT FINDINGS: Prostate-specific
      antigen screening remains controversial, as it is associated with the
      underdetection of clinically significant prostate cancer as well as the
      overdetection and subsequent overtreatment of clinically insignificant disease. A
      diagnostic test that can accurately assess the presence of clinically significant
      prostate cancer and avoid detection of low-risk tumors is needed. Multiparametric
      magnetic resonance imaging (mpMRI) can aid in the detection of clinically
      significant prostate cancer and can be used with fusion-based biopsy platforms to
      target biopsies to specific lesions. However, there are several limitations of
      mpMRI including a modest negative predictive value for high-grade cancer. PSMA
      targeted PET imaging has shown promise as a noninvasive test to aid in the
      detection of clinically significant prostate cancer while providing anatomical
      information to guide targeted biopsies. PSMA-targeted PET in combination with
      mpMRI offers a higher degree of diagnostic accuracy for imaging localized
      prostate cancer than either modality alone. SUMMARY: PSMA-targeted PET imaging
      can aid in the identification of men with clinically significant prostate cancer.
      Further research is needed to determine the full potential of PSMA-targeted
      imaging in both the detection and treatment of localized prostate cancer.

PMID- 30188334
TI  - Human Herpesvirus Alpha Subfamily (Herpes Simplex and Varicella Zoster) Viral
      Pneumonias: CT Findings.
AB  - PURPOSE: The aim of this study was to evaluate CT features of pneumonias caused
      by the alpha Herpesviruses, herpes simplex virus (HSV), and varicella-zoster
      virus (VZV). MATERIALS AND METHODS: By searching the electronic medical record
      from 2005 to 2017, we identified 12 patients with HSV and 15 with VZV pneumonia.
      Four patients with coinfection were excluded from imaging analysis. Two
      radiologists reviewed computed tomography scans (CTs) for findings including
      ground glass and nodules. CTs were assigned to a predominant pattern of crazy
      paving, nodular, or other. RESULTS: The most common risk factor was hematologic
      malignancy, present in 58% of HSV and 47% of VZV patients. Crazy paving was seen
      in 50% of HSV and 31% of VZV cases; a nodular pattern was present in 20% of HSV
      and 69% of VZV patients (P=0.03). CONCLUSIONS: Most patients with alpha
      Herpesvirus pneumonias demonstrated either a crazy paving or nodular pattern on
      CT. The nodular pattern was significantly more common in VZV than in HSV.
      Radiologists should consider these rare infections when evaluating
      immunocompromised patients with these imaging patterns.

PMID- 30188335
TI  - Impact of vascular disease, amputation level, and the mismatch between balance
      ability and balance confidence in a cross sectional study of the likelihood of
      falls among people with limb loss: perception versus reality.
AB  - OBJECTIVE: Investigate impact of balance ability, Activities-specific Balance
      Confidence (ABC), and other self-reported and clinical factors on incidence of
      falls among people with lower-limb loss. DESIGN: Cross-sectional study (N=305)
      with multivariable logistic regression analysis RESULTS: Participants included
      68.3% males with age 55.5+/-14.9; with 50% dysvascular and 56.8% transtibial
      amputations. Average ABC=2.1/4 +/-1.1, balance ability=2.9/4 +/-1.3 and walking
      speed=0.766+/-0.387 m/s. The final model showed fall risk was heightened for
      people with vascular comorbidities (odds ratio [OR]=3.46, 95% confidence interval
      [CI]=1.40-8.54) and better balance (OR=23.29, CI=3.19-170.23); but attenuated for
      people with transfemoral (OR=0.08, CI=0.01-0.82) and vascular amputations
      (OR=0.38, CI=0.15-0.95). Significant interactions existed between age and
      amputation level (OR=1.06, CI=1.02-1.11) and between balance confidence and
      balance ability (OR=0.27, CI=0.13-0.57). CONCLUSIONS: While people with vascular
      amputations were less likely to fall than those with nonvascular amputations,
      people with concurrent vascular comorbidities were more likely to fall than those
      without. People with transfemoral amputations were less likely to fall-however,
      fall risk increased with each year of age compared to people with transtibial
      amputations. People with balance ability >=3.5 fell more often than those with
      lower ability, but people with lower balance ability and mismatched confidence in
      their balance ability had 3.7 times greater fall risk.

PMID- 30188336
TI  - Characterizing, Assessing, and Treating Cognitive Dysfunction in Major Depressive
      Disorder.
AB  - LEARNING OBJECTIVES: After participating in this activity, learners should be
      better able to:* Characterize cognitive dysfunction in patients with major
      depressive disorder.* Evaluate approaches to treating cognitive dysfunction in
      patients with major depressive disorder. ABSTRACT: Cognitive dysfunction is a
      core psychopathological domain in major depressive disorder (MDD) and is no
      longer considered to be a pseudo-specific phenomenon. Cognitive dysfunction in
      MDD is a principal determinant of patient-reported outcomes, which, hitherto,
      have been insufficiently targeted with existing multimodal treatments for MDD.
      The neural structures and substructures subserving cognitive function in MDD
      overlap with, yet are discrete from, those subserving emotion processing and
      affect regulation. Several modifiable factors influence the presence and extent
      of cognitive dysfunction in MDD, including clinical features (e.g., episode
      frequency and illness duration), comorbidity (e.g., obesity and diabetes), and
      iatrogenic artefact. Screening and measurement tools that comport with the
      clinical ecosystem are available to detect and measure cognitive function in MDD.
      Notwithstanding the availability of select antidepressants capable of exerting
      procognitive effects, most have not been sufficiently studied or rigorously
      evaluated. Promising pharmacological avenues, as well as psychosocial,
      behavioral, chronotherapeutic, and complementary alternative approaches, are
      currently being investigated.

PMID- 30188337
TI  - Interoception in Psychiatric Disorders: A Review of Randomized, Controlled Trials
      with Interoception-Based Interventions.
AB  - Interoception, or the process of sensing, interpreting, and integrating internal
      bodily signals, has increasingly been the subject of scientific research over the
      past decade but is still not well known in clinical practice. The aim of this
      article is to review clinical treatment interventions that use interoception, to
      synthesize the current research knowledge, and to identify the gaps where future
      research is needed. We conducted a comprehensive literature search on randomized,
      controlled trials that both include interoception in treatment interventions for
      individuals with psychiatric disorders and measure aspects of interoception using
      self-report measures. Out of 14 randomized, controlled trials identified, 7 found
      that interventions with interoception were effective in ameliorating symptoms.
      These studies included individuals with anxiety disorders, eating disorders,
      psychosomatic disorders, and addictive disorders. All of the intervention studies
      with positive clinical outcomes also demonstrated changes on interoceptive
      measures; however, these measures were often related to specific illness
      symptoms. Interoception may be a mechanism of action in improving clinical
      symptomatology, though studies incorporating general, symptom-independent
      interoceptive measures remain scarce. To further our understanding of the role
      interoception has in psychiatric disorders and their treatment, more studies
      integrating interoceptive measures are needed, along with a clearer definition of
      interoceptive terms used.

PMID- 30188338
TI  - Prescription Benzodiazepine Use Among Older Adults: A Critical Review.
AB  - OBJECTIVES: Despite evidence for many potential risks, use of benzodiazepines
      (BZDs) among older adults is common. The authors evaluated the available evidence
      for BZD effectiveness and tolerability for use in older adults in three
      psychiatric conditions for which BZDs are commonly prescribed: insomnia, anxiety
      disorders, and behavioral and psychological symptoms of dementia. DESIGN:
      Electronic databases, including PubMed/MEDLINE, were searched to identify
      articles that (1) included patients >=50 years of age, (2) focused on patients
      diagnosed with insomnia, anxiety disorders, or behavioral and psychological
      symptoms of dementia, and (3) were either a randomized, placebo-controlled trial
      or a randomized trial comparing a BZD with either another psychotropic medication
      or psychotherapy. RESULTS: Thirty-one studies met the inclusion criteria. Of the
      three clinical indications evaluated, treatment of insomnia had the greatest
      available evidence for use of BZDs among older adults, with 21 of 25 trials
      demonstrating improved sleep outcomes with use of BZDs. Only one trial was found
      to meet eligibility criteria for BZD use in anxiety disorders, demonstrating
      benefit over placebo. Five studies for use in behavioral disturbances in dementia
      were included, of which only one demonstrated improvement over placebo.
      CONCLUSION: This systematic review suggests that BZD prescribing to older adults
      is significantly in excess of what the available evidence suggests is
      appropriate. Future trials should focus on efforts to reduce both acute and
      chronic BZD use among older adults while improving access to effective non
      pharmacologic treatment alternatives.

PMID- 30188341
TI  - Animal Models in Psychiatric Disease: A Circuit-Search Approach.

PMID- 30188340
TI  - Uncharted Waters: Developing Mental Health Services for Survivors of Domestic
      Human Sex Trafficking.
AB  - In recent years, heightened attention has been paid to commercial sexual
      exploitation, including domestic human sex trafficking (HST), with mental health
      concerns named the most dominant health concern among survivors. Human sex
      trafficking is associated with significant and long-term mental health
      consequences. Research to date has emphasized ways to identify survivors in
      health care settings. Once identified, however, few specialized services are
      available to help survivors exit and recover. The current services infrastructure
      for HST has been compared to the disjointed social response to intimate partner
      violence before the women's movement helped develop a system of battered women's
      shelters. Although research has highlighted the need for a multidisciplinary and
      interagency response to HST, including mental health care, best practices have
      not yet been formulated. Furthermore, available services are fragmented across
      sectors. With psychology and psychiatry taking tentative steps to develop
      services for HST survivors, this article identifies six principles to help avoid
      a fragmented and potentially retraumatizing clinical and systemic response. The
      overarching goal is to design services that are flexible, accessible, trauma
      informed, survivor driven, responsive to stages of change, multidisciplinary, and
      enduring, especially given the centrality of healthy attachments and community in
      trauma recovery. Principles are derived from the limited available research on
      HST services and from examples of efficacious interventions for patient groups
      with similar characteristics. The discussion is also informed by composite
      clinical vignettes from a specialized clinic for adult survivors of HST, housed
      in a major teaching hospital. Finally, practice recommendations and strategies
      for building interdisciplinary collaborations are discussed.

PMID- 30188342
TI  - What is new in HIES? Recent insights from the interface of primary immune
      deficiency and atopy.
AB  - PURPOSE OF REVIEW: Understanding the pathophysiology of monogenic primary
      immunodeficiency (PID) with atopic presentation has pivotal implications for
      intervention strategies and potentially wider polygenic atopic-related traits.
      This review will discuss advances in gene discovery arising from monogenic
      defects at the interface between PID and atopy, notably the hyper-IgE syndromes.
      RECENT FINDINGS: Key molecular pathways underlying development of primary atopic
      diseases have recently been proposed. We test this classification through
      reviewing novel genes reported in the last 2 years and compare insights from
      pathway-analysis of genome-wide association studies (GWAS) of atopic-related
      traits.Growing access to next-generation sequencing (NGS) has resulted in a surge
      in gene discovery, highlighting the utility and some pitfalls of this approach in
      clinical practice. The variability of presenting phenotypes reveals important
      gene-dosage effects. This has important implications for therapeutic strategies
      such as protein stabilization and modulators of JAK-STAT or TH2-cytokine
      signalling. We also consider the therapeutic implications raised by CARD11
      deficiency, and wider applications of NGS including polygenic risk score in
      atopy. SUMMARY: Disorders presenting at the interface between PID and allergy are
      often difficult to diagnose, with serious consequences if missed. Application of
      NGS has already provided critical insights to pathways enabling targeted
      therapeutic interventions, and potential wider translation to polygenic
      disorders.

PMID- 30188339
TI  - Development of a Boston Treatment Program for Youth at Clinical High Risk for
      Psychosis: Center for Early Detection, Assessment, and Response to Risk (CEDAR).
AB  - Over the past two decades, increasing attention has been given to the importance
      of early intervention for psychosis. This article describes the development of
      the Center for Early Detection, Assessment and Response to Risk (CEDAR), which
      focuses on early identification and treatment of youth at clinical high risk for
      psychosis. There are relatively few models in the United States for such
      programs, and we present our developmental story, focusing mainly on the CEDAR
      Clinic, as a case study of how such a program can develop. We describe the
      rationale, infrastructure, and services provided at the CEDAR Clinic, and present
      some descriptive data from the CEDAR Clinic through 2016. A case example is
      provided to illustrate treatment at CEDAR. We hope that the cultural history of
      our program's development is informative for clinicians and policy makers as one
      model of how to build an early intervention service. We believe that this article
      is timely in view of the growing momentum in the United States for developing
      programs for intervening as early as possible for youth at clinical high risk for
      psychosis.

PMID- 30188343
TI  - Tibiofemoral Contact Mechanics With Horizontal Cleavage Tears and Treatment of
      the Lateral Meniscus in the Human Knee: An In Vitro Cadaver Study.
AB  - BACKGROUND: Partial meniscectomy is one of the most commonly performed
      orthopaedic procedures for a meniscus tear. Decreased contact area and increased
      contact pressure have been seen in partial meniscectomies from treatment of
      various types of meniscal tears; however, the biomechanical effect of a
      horizontal cleavage tear in the lateral meniscus and subsequent treatment are
      unknown. QUESTIONS/PURPOSES: This study asked whether a horizontal cleavage tear
      of the lateral meniscus, resecting the inferior leaf, and further resecting the
      superior leaf would (1) decrease contact area and (2) increase peak contact
      pressure. METHODS: Eleven fresh-frozen human cadaveric knees were evaluated under
      five conditions of intact meniscus, horizontal cleavage tear, inferior leaf
      resection, and resection of the inferior and superior leaves of the lateral
      meniscus. Tibiofemoral contact area and pressure were measured at 0 degrees  and
      60 degrees  knee flexion under an 800-N load, normalized to that at the intact
      condition of the corresponding knee flexion, and compared across the five
      previously described conditions. RESULTS: At 0 degrees  knee flexion, normalized
      contact area with inferior leaf resection (65.4% +/- 14.1%) was smaller than that
      at the intact condition (100% +/- 0.0%, p < 0.001); smaller than horizontal
      cleavage tear (94.1% +/- 5.8%, p = 0.001) contact area; and smaller than repaired
      horizontal tear (92.8% +/- 8.2%, p = 0.001) contact area. Normalized contact area
      with further superior leaf resection (50.5% +/- 7.3%) was smaller than that at
      the intact condition (100% +/- 0.0%, p < 0.001); smaller than horizontal cleavage
      tear (94.1% +/- 5.8%, p < 0.001) contact area; and smaller than repaired
      horizontal tear (92.8% +/- 8.2%, p < 0.001) contact area. At 60 degrees  flexion,
      normalized contact area with inferior leaf resection (76.1% +/- 14.8%) was
      smaller than that at the intact condition (100% +/- 0.0%, p = 0.004); smaller
      than horizontal cleavage tear (101.8% +/- 7.2%, p = 0.006) contact area; and
      smaller than repaired horizontal tear (104.0% +/- 13.3%, p < 0.001) contact area.
      Normalized contact area with further superior leaf resection (52.1% +/- 16.7%)
      was smaller than that at the intact condition (100% +/- 0.0%, p < 0.001); smaller
      than horizontal cleavage tear (101.8% +/- 7.2%, p < 0.001) contact area; and
      smaller than repaired horizontal tear (104.0% +/- 13.3%, p < 0.001) contact area.
      At 60 degrees  flexion, contact area with both leaf resection (52.1% +/- 16.7%)
      was smaller than that with inferior leaf resection (76.1% +/- 14.8%, p = 0.039).
      At 0 degrees  knee flexion, peak pressure increased to 127.0% +/- 22.1% with
      inferior leaf resection (p = 0.026) and to 138.6% +/- 24.3% with further superior
      leaf resection (p = 0.002) compared with that at the intact condition (100% +/-
      0.0%). At 60 degrees  flexion, compared with that at the intact condition (100%
      +/- 0.0%), peak pressure increased to 139% +/- 33.6% with inferior leaf resection
      (p = 0.035) and to 155.5% +/- 34.7% (p = 0.004) with further superior leaf
      resection. CONCLUSIONS: Resection of the inferior leaf or both leaves of the
      lateral meniscus after a horizontal cleavage tear resulted in decreased contact
      area and increased peak contact pressure at 0 degrees  and 60 degrees  knee
      flexion. CLINICAL RELEVANCE: In vitro resection of one or both leaves of a
      horizontal cleavage tear of the lateral meniscus causes increases in peak
      pressure, consistent with other types of partial meniscectomies associated in a
      clinical setting with excessive loading and damage to knee cartilage. Clinical
      outcomes in patients undergoing partial leaf meniscectomy could confirm this
      theory. Avoidance of resection may be relatively beneficial for long-term
      function. The findings of this in vitro study lend biomechanical support for
      nonoperative management.

PMID- 30188344
TI  - What Factors Are Associated With Disability After Upper Extremity Injuries? A
      Systematic Review.
AB  - BACKGROUND: Psychosocial factors are key determinants of health after upper
      extremity injuries. However, a systematic review is needed to understand which
      psychosocial factors are most consistently associated with disability and how the
      language, conceptualization, and types of measures used to assess disability
      impact these associations in upper extremity injuries. QUESTIONS/PURPOSES: (1)
      What factors are most consistently associated with disability after upper
      extremity injuries in adults? (2) What are the trends in types of outcome
      measures and conceptualization of disability in patients' upper extremity
      injuries? METHODS: We searched multiple electronic databases (PubMED, OVIDSP,
      PsycInfo, Google Scholar, ISI Web of Science) between January 1, 1996, and
      December 31, 2016, using terms related to the "upper extremity", "outcome
      measurement", and "impairment, psychological, social or symptomatic" variables.
      We included all studies involving adult patients with any musculoskeletal injury
      and excluded those that did not use patient-reported outcome measures. We
      identified and screened 9339 studies. Of these, we retained 41 studies that
      involved conditions ranging from fractures to soft tissue injuries in various
      regions of the arm. We conducted quality assessment using a 10-item validated
      checklist and a five-tier strength of evidence assessment. We used the Preferred
      Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) criteria and
      registered the review before performing our search (PROSPERO: CRD42017054048).
      None of the authors received any funding to perform this work. RESULTS:
      Disability after upper extremity injury was most consistently associated with
      depression (21 cohorts), catastrophic thinking (13 cohorts), anxiety (11
      cohorts), pain self-efficacy (eight cohorts), and pain interference (seven
      cohorts). Social and demographic factors were also associated with disability.
      Measures of impairment such as ROM and injury severity were least associated with
      disability. There has been a gradual increase in use of region or condition
      specific patient-reported outcome measures and measures of psychological, social,
      and symptomatic factors over a period since the introduction of the World Health
      Organization (WHO) International Classification of Functioning, Disability and
      Health (ICF) around 2000. Approximately 17% of studies (n = 454 of 2628) had
      instances of unclear, conflicting, or inappropriate terminology and 11% of
      studies (n = 257 of 2628) involved misrepresentations of outcome measures related
      to disability. CONCLUSIONS: Psychologic and social factors are most consistently
      associated with disability than factors related to impairment. Further research
      involving the assessment of depression, anxiety, and coping strategies in cohorts
      with specific injuries may support decision-making regarding the provision of
      emotional support and psychologic therapies during recovery. Using the WHO ICF
      framework to conceptualize disability is key in increasing strength of evidence
      and allowing accurate comparisons of research in this field. LEVEL OF EVIDENCE:
      Level IV, therapeutic study.

PMID- 30188345
TI  - Letter to the Editor: Are There Age- and Sex-related Differences in Spinal
      Sagittal Alignment and Balance Among Taiwanese Asymptomatic Adults?

PMID- 30188346
TI  - Letter to the Editor: Art in Science: Jusepe de Ribera's Puzzle in The Clubfoot.

PMID- 30188347
TI  - CORR Insights(r): Neoadjuvant Chemotherapy Followed by Delayed Surgery: Is it
      Necessary for All Patients With Nonmetastatic High-Grade Pelvic Osteosarcoma?

PMID- 30188348
TI  - CORR(r) Curriculum - Orthopaedic Education: Reconsidering the ACGME Orthopaedic
      Milestones.

PMID- 30188349
TI  - Reply to the Letter to the Editor: Are There Age- and Sex-related Differences in
      Spinal Sagittal Alignment and Balance Among Taiwanese Asymptomatic Adults?

PMID- 30188350
TI  - Incidence of Viremia With DNA Viruses in Oncology Patients With Febrile
      Neutropenia.
AB  - BACKGROUND: Although febrile neutropenia (FN) is one of the most common adverse
      events produced by chemotherapy, its microbiological etiology is determined for
      only 15% to 30% of cases. OBJECTIVES: We investigated the rate of viremia with
      common DNA viruses in patients with FN. STUDY DESIGN: From June 2012 to April
      2014, 72 blood samples from 24 patients receiving chemotherapy, who experienced
      FN episodes, were examined for the presence of herpes viruses and other DNA
      viruses. We used real-time polymerase chain reaction assays to detect herpes
      simplex virus type 1 and 2, varicella zoster virus, Epstein-Barr virus,
      cytomegalovirus, human herpes virus types 6 and 7, BK virus and human parvovirus
      B19 (B19). RESULTS: Viruses were identified in 14 of 72 samples (19.4%). The
      detected etiological agents were BK virus (5 episodes), human herpes virus type 6
      (4 episodes), B19 (4 episodes), Epstein-Barr virus (2 episodes), and
      cytomegalovirus (1 episode). CONCLUSIONS: Our results indicate that viral
      infections are common causes in patients with FN. Therefore, viruses may be
      responsible for FN in a large proportion of patients in whom a causative
      microorganism could not be identified, and this viral etiology may explain their
      poor response to antibiotic therapy.

PMID- 30188351
TI  - Acquired Pure Red Cell Aplasia and Acquired Amegakaryocytic Thrombocytopenia
      Associated With Clonal Expansion of T-Cell Large Granular Lymphocytes in a
      Patient With Lipopolysaccharide-responsive Beige-like Anchor (LRBA) Protein
      Deficiency.
AB  - Acquired pure red cell aplasia and acquired amegakaryocytic thrombocytopenic
      purpura are rare in children. Similarly, clonal expansion of T-cell large
      granular lymphocytes is infrequently seen in pediatrics. Lipopolysaccharide
      responsive beige-like anchor (LRBA) protein deficiency is a recently described
      immunodeficiency syndrome that has been associated with inflammatory bowel
      disease and autoimmune phenomena such as Evans syndrome. Here, we describe a
      patient with LRBA deficiency who developed acquired pure red cell aplasia and
      acquired amegakaryocytic thrombocytopenic purpura associated with expansion of
      clonal T-cell large granular lymphocytes. This has not been described in the
      literature previously and adds to the knowledge on the spectrum of manifestations
      of LRBA deficiency.

PMID- 30188352
TI  - Analysis of Mesenchymal Stromal Cell Engraftment After Allogeneic HSCT in
      Pediatric Patients: A Large Multicenter Study.
AB  - The mesenchymal stem cell (MSC) role after allogeneic hematopoietic stem cell
      transplantation (HSCT) is still a matter of debate; in particular, MSC
      engraftment in recipient bone marrow (BM) is unclear. A total of 46 patients were
      analyzed for MSC and hemopoietic stem cell engraftment after HSCT. The majority
      of patients had the BM as the stem cell source, and acute leukemia was the main
      indication for HSCT. Mesenchymal and hematopoietic stem cell chimerism analysis
      was carried out through specific polymorphic tandemly repeated regions. All
      patients reached complete donor engraftment; no evidence of donor-derived MSC
      engraftment was noted. Our data indicate that MSCs after HSCT remain of recipient
      origin despite the following: (i) myeloablative conditioning; (ii) the stem cell
      source; (iii) the interval from HSCT to BM analysis; (iv) the underlying disease
      before HSCT; and (v) the patients' or the donors' age at HSCT.

PMID- 30188353
TI  - Older Adults' Experience Using Patient Portals in Communities: Challenges and
      Opportunities.
AB  - Patient portals can be beneficial for older adults who manage their own health.
      However, there is a lack of research on older adults' experience using patient
      portals in the community. The aim of this study was to assess older adults'
      perceived usability of patient portals they currently use. This was a secondary
      data analysis using selected baseline data from an online trial that tested the
      effects of a 3-week Theory-Based Patient Portal eLearning Program, and included
      272 older adults recruited online. Data were analyzed using descriptive
      statistics and content analysis. Most participants owned patient portal accounts
      (n = 194 [71.3%]). Self-efficacy for using patient portals was relatively low
      (mean, 27.1; range, 0-40), and perceived usability of patient portals was also
      low (mean, 28.7; range, 6-42). The most-favored features of patient portals were
      review of medical information and eMessaging. The main difficulties in using
      patient portals were associated with login/access and specific portal functions.
      Managing multiple patient portals was a particular challenge for many
      participants. Findings from this study indicate the importance of providing
      proper levels of training and technical support to older adults to maximize use
      and improve outcomes of patient portal implementation.

PMID- 30188354
TI  - Dopamine and reward: a view from the prefrontal cortex.
AB  - The prefrontal cortex (PFC) is a heterogeneous area that is critical to reward
      based decision-making. In particular, the dorsal anterior cingulate cortex,
      ventromedial PFC and orbitofrontal cortex are frequently implicated in different
      aspects of choice behaviour. These regions receive projections from midbrain
      dopamine (DA) neurons and, in turn, project to other key dopaminergic regions
      such as the striatum. However, our current understanding of the role of DA in
      reward-based processes is based mainly on studies of midbrain dopaminergic
      neurons and striatal DA release from nonhuman animal models. An important gap in
      the literature surrounds the precise functions of DA release in the PFC,
      particularly in humans. A priority for future research will be to integrate, both
      computationally and biologically, the seemingly disparate value representations
      across different nodes within the reward-processing network. Such models should
      aim to define the functional interactions between the PFC and basal ganglia,
      through which dopaminergic neurotransmission guides reward-based behaviour.

PMID- 30188355
TI  - Nutritional Status is Associated With Severe Dementia and Mortality: The Cache
      County Dementia Progression Study.
AB  - PURPOSE: Studies have reported faster cognitive/functional decline in persons
      with dementia (PWD) with malnutrition. We investigated whether baseline
      nutritional status predicted severe dementia and mortality in a population-based
      sample. PATIENTS: A maximum of 300 PWD were assessed annually for up to 8.6
      years. METHODS: Nutritional status was assessed using a modified Mini-Nutritional
      Assessment (mMNA). Severe dementia was defined as: "severe" rating on the
      Clinical Dementia Rating or Mini-Mental State Examination score <=10. Using Cox
      proportional hazards models, we examined the association between baseline mMNA
      score (or its subcomponents) with each outcome. Covariates included demographics;
      dementia onset age, type, and duration; APOE genotype; and residency with
      caregiver. RESULTS: Compared with "well-nourished," "malnourished" PWD had 3-4
      times the hazard of severe dementia [hazard ratio (HR), 4.31; P=0.014] and death
      (HR, 3.04; P<0.001). Those "at risk for malnutrition" had twice the hazard of
      severe dementia (HR, 1.98; P=0.064) and 1.5 times the hazard of death (HR, 1.46;
      P=0.015). mMNA subcomponents of food group intake, weight loss, body mass index,
      mobility, health status, protein consumption, and mid-arm circumference predicted
      one or both outcomes. CONCLUSIONS: Nutritional status is an important predictor
      of clinical outcomes in dementia and may provide an avenue for intervention.

PMID- 30188357
TI  - Deep vs. moderate neuromuscular blockade during laparoscopic surgery: A
      systematic review and meta-analysis.
AB  - BACKGROUND: Previous studies have reported that deep neuromuscular block
      (posttetanic-count 1 to 2 twitches) improves surgical conditions during
      laparoscopy compared with moderate block (train-of-four count: 1 to 2 twitches).
      However, comparisons of surgical conditions were made using different scales and
      assessment intervals with variable results. OBJECTIVE: To explore the
      heterogeneity of previous comparisons between deep and moderate neuromuscular
      block. DESIGN: Systematic review and meta-analysis of randomised controlled
      trials (RCTs). DATA SOURCES: Medline, EMBASE and Cochrane Central Register of
      Controlled Trials were searched from inception to October 2017. ELIGIBILITY
      CRITERIA: Our meta-analysis included RCTs comparing the effects of deep with
      moderate neuromuscular block on surgical field conditions during laparoscopic
      surgery. The frequency of excellent or good operating conditions on a surgical
      rating scale was compared. Heterogeneity was assessed by subgroup analyses.
      RESULTS: Eleven RCTs involving 844 patients were included. On the surgical rating
      scale, the frequency of excellent or good operating conditions was higher with
      deep block compared with a moderate block (odds ratio 2.83, 95% confidence
      interval 1.34 to 5.99, P = 0.007, I = 59%). We analysed surgical rating according
      to the number of assessments made. There was a significant difference in surgical
      rating with multiple assessments, but no difference when the assessment was made
      on only one occasion. A significant difference in rating was noted with variable
      abdominal pressures; there was no significant difference with the same fixed
      abdominal pressure. Trial sequential analysis demonstrated that the cumulative z
      curve crossed the O'Brien-Fleming significance boundary. However, required
      information size was not achieved. CONCLUSION: Deep block was associated with
      excellent or good surgical rating more frequently than moderate block. However,
      this finding was not consistent on subgroup analyses based on frequencies of
      assessment of surgical conditions and abdominal pressure. Further studies are
      required to address the heterogeneity and power shortage demonstrated by the
      trial sequential analysis.

PMID- 30188356
TI  - A Novel Nonsense Angiogenin Mutation is Associated With Alzheimer Disease.

PMID- 30188360
TI  - Blood pressure monitor validation, calibration, and community pharmacy practice:
      a pilot cross-sectional survey in Hampshire, UK.

PMID- 30188358
TI  - Evaluating the Prognosis of Ischemic Stroke Using Low-Dose Multimodal Computed
      Tomography Parameters in Hyperacute Phase.
AB  - PURPOSE: The aim of this study was to evaluate the potential value of low-dose
      multimodal computed tomography (CT) in predicting prognosis of acute ischemic
      stroke (AIS) within 6 hours. METHODS: The admission "one-stop-shop" multimodal CT
      examination, including noncontrast CT (NCCT), low-dose CT perfusion, and CT
      angiography (CTA), was performed in patients with symptoms of stroke within 6
      hours. Noncontrast CT, CTA source image (CTA-SI), cerebral blood flow (CBF),
      cerebral blood volume (CBV), time to peak (TTP), and mean transit time (MTT) maps
      were studied using Alberta Stroke Program Early CT Score (ASPECTS). The regional
      leptomeningeal collateral (rLMC) score (0-20) was dichotomized into 2 groups:
      good (11-20) and poor (0-10) rLMC. Poor functional outcomes were defined by a
      modified Rankin scale score of 3 to 6. RESULTS: One hundred forty-four patients
      were ultimately selected; 43.8% of them showed poor functional outcomes. They had
      lower ASPECTSs on NCCT, CTA-SI, CBV, CBF, TTP, and MTT, and poor rLMC was more
      frequently associated with poor functional outcomes (all P < 0.001). In the
      multivariate analysis for AIS patients with conservative treatment, CTA-SI
      ASPECTS 6 or less (odds ratio [OR], 5.9; 95% confidence interval [95% CI], 1.9
      18.4; P = 0.002) and poor collaterals (OR, 5.0; 95% CI, 1.3-15.4; P = 0.017), CBV
      ASPECTS 6 or less (OR, 8.0; 95% CI, 2.7-24.0; P < 0.001), CBF-ASPECTS 4 or less
      (OR, 8.0; 95% CI, 2.0-31.5; P = 0.003), MTT-ASPECTS<=3 (OR, 5.8; 95% CI, 1.8
      18.1; P = 0.003), TTP-ASPECTS 4 or less (OR, 5.0; 95% CI, 1.6-15.1; P = 0.005),
      and NCCT-ASPECTS 8 or less (OR, 5.9; 95% CI, 1.7-20.4; P = 0.005) were
      significantly associated with poor functional outcome. In the multivariate
      analysis for AIS patients with thrombolysis, CTA-SI-ASPECTS 6 or less (OR, 27.5;
      95% CI, 2.9-262.3; P = 0.004), poor collaterals (OR, 28.0; 95% CI, 2.8-283.0; P <
      0.028), and CBV-ASPECTS 6 or less (OR, 18.0; 95% CI, 3.0-107.7; P = 0.002) were
      associated with poor functional outcomes. Furthermore, the area under the curve
      (AUC) of the combination of CTA-SI-ASPECTS 6 or less, poor collaterals, and CBV
      ASPECTS 6 or less (AUC, 0.87) was greater than that for any single parameter
      alone: CTA-SI-ASPECTS 6 or less (AUC, 0.80; P < 0.001), poor collaterals (AUC,
      0.76; P < 0.001), and CBV-ASPECTS 6 or less (AUC, 0.81; P = 0.002). CONCLUSIONS:
      The combination of CTA-SI-ASPECTS, collaterals, and CBV-ASPECTS may improve
      predictive power compared with a single parameter alone.

PMID- 30188361
TI  - Diagnostic and Predictive Immunohistochemistry for Non-Small Cell Lung
      Carcinomas.
AB  - Non-small cell lung carcinoma (NSCLC) accounts for significant morbidity and
      mortality worldwide, with most patients diagnosed at advanced stages and managed
      increasingly with targeted therapies and immunotherapy. In this review, we
      discuss diagnostic and predictive immunohistochemical markers in NSCLC, one of
      the most common tumors encountered in surgical pathology. We highlight 2 emerging
      diagnostic markers: nuclear protein in testis (NUT) for NUT carcinoma; SMARCA4
      for SMARCA4-deficient thoracic tumors. Given their highly aggressive behavior,
      proper recognition facilitates optimal management. For patients with advanced
      NSCLCs, we discuss the utility and limitations of immunohistochemistry (IHC) for
      the "must-test" predictive biomarkers: anaplastic lymphoma kinase, ROS1,
      programmed cell death protein 1, and epidermal growth factor receptor. IHC using
      mutant-specific BRAF V600E, RET, pan-TRK, and LKB1 antibodies can be orthogonal
      tools for screening or confirmation of molecular events. ERBB2 and MET
      alterations include both activating mutations and gene amplifications, detection
      of which relies on molecular methods with a minimal role for IHC in NSCLC. IHC
      sits at the intersection of an integrated surgical pathology and molecular
      diagnostic practice, serves as a powerful functional surrogate for molecular
      testing, and is an indispensable tool of precision medicine in the care of lung
      cancer patients.

PMID- 30188362
TI  - Effects of EPO on Blood Parameters and Running Performance in Kenyan Athletes.
AB  - INTRODUCTION: Recombinant human erythropoietin (rHuEpo) administration enhances
      oxygen carrying capacity and performance at sea level. It remains unknown whether
      similar effects would be observed in chronic altitude-adapted endurance runners.
      The aim of this study was to assess the effects of rHuEpo on haematological and
      performance parameters in chronic altitude-adapted endurance runners as compared
      to sea level athletes. METHODS: Twenty well-trained Kenyan endurance runners
      (KEN) living and training at ~2,150 m received rHuEpo injections of 50 IU[BULLET
      OPERATOR]kg-1 body mass every 2 days for 4 weeks and responses compared to
      another cohort (SCO) that underwent an identical protocol at sea level. Blood
      samples were obtained at baseline, during rHuEpo administration and 4 weeks after
      the final injection. A maximal oxygen uptake ( O2max) test and 3,000 m time trial
      was performed before, immediately after and 4 weeks after the final rHuEpo
      injection. RESULTS: Haematocrit (HCT) and haemoglobin concentration (HGB) were
      higher in KEN compared to SCO prior to rHuEpo but similar at the end of
      administration. Prior to rHuEpo administration, KEN had higher VO2max and faster
      time trial performance compared to SCO. Following rHuEpo administration, there
      was a similar increase in VO2max and time trial performance in both cohorts; most
      effects of rHuEpo were maintained 4 weeks after the final rHuEpo injection in
      both cohorts. CONCLUSION: Four weeks of rHuEpo increased the HGB and HCT of
      Kenyan endurance runners to a lesser extent than in SCO (~17% vs ~10%,
      respectively) and these alterations were associated with similar improvements in
      running performance immediately after the rHuEpo administration (~5%) and 4 weeks
      after rHuEpo (~3%).

PMID- 30188363
TI  - Type 1 Muscle Fiber Hypertrophy after Blood Flow-restricted Training in
      Powerlifters.
AB  - PURPOSE: To investigate the effects of blood flow restricted resistance exercise
      (BFRRE) on myofiber areas (MFA), number of myonuclei and satellite cells (SC),
      muscle size and strength in powerlifters. METHODSSeventeen national level
      powerlifters (25+/-6 yrs [mean+/-SD], 15 men) were randomly assigned to either a
      BFRRE group (n=9) performing two blocks (week 1 and 3) of five BFRRE front squat
      sessions within a 6.5-week training period, or a conventional training group
      (Con; n=8) performing front squats at ~70% of one-repetition maximum (1RM). The
      BFRRE consisted of four sets (first and last set to voluntary failure) at ~30% of
      1RM. Muscle biopsies were obtained from m. vastus lateralis (VL) and analyzed for
      MFA, myonuclei, SC and capillaries. Cross sectional areas (CSA) of VL and m.
      rectus femoris (RF) were measured by ultrasonography. Strength was evaluated by
      maximal voluntary isokinetic torque (MVIT) in knee extension and 1RM in front
      squat. RESULTS: BFRRE induced selective type I fiber increases in MFA (BFRRE: 12%
      vs. Con: 0%, p<0.01) and myonuclear number (BFRRE: 17% vs. Con: 0%, p=0.02). Type
      II MFA was unaltered in both groups. BFRRE induced greater changes in VL CSA
      (7.7% vs. 0.5%, p=0.04), which correlated with the increases in MFA of type I
      fibers (r=0.81, p=0.02). No group differences were observed in SC and strength
      changes, although MVIT increased with BFRRE (p=0.04), whereas 1RM increased in
      Con (p=0.02).Two blocks of low-load BFRRE in the front squat exercise resulted in
      increased quadriceps CSA associated with preferential hypertrophy and myonuclear
      addition in type 1 fibres of national level powerlifters.

PMID- 30188364
TI  - Effect of Primary Stability and Soft- and Hard-Tissue Thickness on Marginal Bone
      Loss: A Prospective Pilot Study.
AB  - OBJECTIVE: To compare prospectively the effect of different insertion torques
      (ITs) on marginal bone stability and study the effect of soft-tissue and buccal
      bone thickness as confounding factors while using a 3-dimensional radiographic
      evaluation. MATERIALS AND METHODS: Thirty-nine implants were placed in 22
      patients. IT, soft-tissue thickness, and buccal bone thickness were recorded at
      implant placement. Marginal bone loss was evaluated on individualized periapical
      radiographs and cone-beam computed tomography at 1 year after loading. RESULTS:
      Three groups of implants emerged based on their IT: group I (<30 Ncm), group II
      (between 30-45 Ncm), and group III (>45 Ncm). Soft-tissue thickness was <=2 mm in
      10 implants (25.6% thin biotype) and more than 2 mm in 29 implants (74.4% thick
      biotype). No significant difference in marginal bone loss was found for different
      IT and different soft-tissue thickness. A significant correlation was found
      between initial buccal bone thickness (>=2 mm or <2 mm) and marginal bone loss at
      1 year. CONCLUSIONS: IT and mucosal tissue thickness did not influence marginal
      bone loss. Buccal bone thickness of >=2 mm was associated with a minimal marginal
      bone remodeling.

PMID- 30188365
TI  - Vital Bone Formation After Grafting of Autogenous Bone and Biphasic Calcium
      Phosphate Bioceramic in Extraction Sockets of Rats: Histological, Histometric,
      and Immunohistochemical Evaluation.
AB  - PURPOSE: The study aimed to investigate through histology, histometry, and
      immunohistochemistry the vital bone formation after grafting of biphasic calcium
      phosphate bioceramic (BC) in combination with calvarial autogenous bone into the
      dental sockets of rats. MATERIALS AND METHODS: Forty-five male rats were
      submitted to upper right incisor extraction and divided according to the grafted
      material in: control, bioceramic (BC), and bioceramic + autogenous bone (BC +
      AB). The animals were killed 7, 21, and 42 days after surgery for histological,
      histometric, and immunohistochemistry analysis. RESULTS: Histomorphometric
      results demonstrated, for BC + AB group, formation of trabecular bone between the
      particles of BCs and autogenous bone, connecting them, as well as higher
      percentage of vital bone in comparison with BC. Immunohistochemical reactions
      showed intense labeling for Runx2-positive cells in the group BC + AB.
      CONCLUSIONS: Autogenous bone was able to stimulate bone turnover enabling a
      larger amount of vital bone synthesis and can be recommended as a viable grafting
      material in combination with synthetic biphasic BC.

PMID- 30188366
TI  - Ethical Use of Student Profiles to Predict and Prevent Development of Depression
      Symptoms During Medical School.
AB  - Research investigations have repeatedly shown that medical school can be a period
      of high stress and deteriorating mental health for many students. There is a
      critical need for systematic guidance on how to personalize prevention and
      treatment programming to help those students at highest risk. The authors of this
      Invited Commentary respond to the report by Dyrbye and colleagues, published in
      this issue of Academic Medicine, that proposes a prognostic index to predict risk
      of developing depression symptoms in medical students. The commentary authors
      applaud Dyrbye and her co-authors for their innovative approach: their findings
      provide substantial insights relevant to the critical goal of enhancing medical
      student wellbeing. However, evidence indicates that students who identify as
      members of racial, ethnic, sexual and/or gender minority groups are at heightend
      risk of depression, so any program that profiles students in relation to their
      mental health symptoms must be proactive in ensuring that its efforts do not
      perpetuate stigma, marginalization, and discrimination for these underrepresented
      and potentially vulnerable groups. The commentary authors suggest practices for
      ethically implementing recommended wellnesss programs while maintaining an
      inclusive learning environment that respects personal privacy and incorporates
      transparent consent practices.

PMID- 30188367
TI  - A Prognostic Index to Identify the Risk of Developing Depression Symptoms Among
      U.S. Medical Students Derived From A National, Four-Year Longitudinal Study.
AB  - PURPOSE: To determine baseline individual and school-related factors associated
      with increased risk of developing depression symptoms by year four (Y4) of
      medical school, and to develop a prognostic index that stratifies risk of
      developing depression symptoms (Depression-PI) among medical students. METHOD:
      The authors analyzed data from 3,743 students (79% of 4,732) attending 49 U.S.
      medical schools who completed baseline (2010) and Y4 (2014) surveys. Surveys
      included validated scales measuring depression, stress, coping, and social
      support. The authors collected demographics and school characteristics and
      conducted multivariate analysis to identify baseline factors independently
      associated with Y4 depression symptoms. They used these factors to create a
      prognostic index for developing depression. They randomly divided the data into
      discovery (n = 2,455) and replication (n = 1,288) datasets and calculated c
      statistics (c). RESULTS: The authors identified eight independent prognostic
      factors for experiencing depression symptoms during training within the discovery
      dataset: age, race, ethnicity, tuition, plus baseline depression symptoms,
      stress, coping behaviors, and social support. The Depression-PI stratified four
      risk groups. Compared to the low risk group, those in the intermediate, high, and
      very high risk group had an odds ratio of developing depression of, respectively,
      1.75, 3.98, and 9.19 (c = 0.71). The replication dataset confirmed the risk
      groups. CONCLUSIONS: Demographics, tuition, depression symptoms, stress, coping
      behaviors, and social support at baseline are independently associated with the
      risk of developing depression during training among U.S. medical students. By
      stratifying students into four risk groups, the Depression-PI may allow for a
      tiered primary prevention approach.

PMID- 30188368
TI  - Using the Clerkship Shelf Exam Score as a Qualification for an Overall Clerkship
      Grade of Honors: A Valid Practice or Unfair to Students?
AB  - Most clerkships require medical students to pass the National Board of Medical
      Examiners (NBME) subject (shelf) exam in order to pass the clerkship. Many use
      the NBME's recommended honors cut score on the shelf exam to determine medical
      student eligibility for an overall clerkship grade of honors. This use of a
      conjunctive scoring model for determining honors is inconsistent with the logic
      behind the intended use of this model for making pass/fail determinations.
      Further, many clerkships use grading systems that employ both this conjunctive
      model for honors eligibility and a compensatory scoring model for determining the
      overall clerkship grade. For students who fall short of the shelf exam honors cut
      score, such a grading system effectively increases the weighting of shelf exam
      performance and decreases the clerkship's transparency about the weighting of
      performance on other assessments toward the clerkship composite score and overall
      grade. It may also lead to contradictory grading results in which student B has a
      higher composite score than student A, yet student B receives a lower overall
      grade. The author illustrates how to calculate a weight for shelf exam
      performance that would be fairer to students and would help create a more
      transparent weighting scheme for the grading system. The author recommends
      clerkships restructure their grading systems so that shelf exam honors
      eligibility cut scores are not used as conjunctive criteria for determining
      overall clerkship grades of honors. A reexamination of the NBME's practice of
      suggesting honors-eligibility cut scores for shelf exams is also recommended.

PMID- 30188369
TI  - Employing a Root Cause Analysis Process to Improve Examination Quality.
AB  - PROBLEM: Multiple-choice question (MCQ) examinations represent a primary mode of
      assessment used by medical schools. It can be challenging for faculty to produce
      content-aligned, comprehensive, and psychometrically sound MCQs. Despite best
      efforts, sometimes there are unexpected issues with examinations. Assessment best
      practices lack a systematic way to address gaps when actual and expected outcomes
      do not align. APPROACH: The authors propose using root cause analysis (RCA) to
      systematically review unexpected educational outcomes. Using a real-life example
      of a class's unexpectedly low reproduction examination scores (University of
      Michigan Medical School, 2015), the authors describe their RCA process, which
      included a system flow diagram, a fishbone diagram, and an application of the 5
      Whys to understand the contributors and reasons for the lower than expected
      performance. Using this RCA approach, the authors identified multiple
      contributing factors that potentially led to the low examination scores. These
      included: lack of examination QI for poorly constructed items, content-question
      and pedagogy-assessment misalignment, and other issues related to environment and
      people. OUTCOMES: As a result of the RCA, the authors worked with stakeholders to
      address these issues and develop strategies to prevent similar systematic issues
      from reoccurring. For example, a more robust examination QI process was
      developed. NEXT STEPS: RCA approach in health care is grounded in practice and
      can be easily adapted for assessment. Because this is a novel use of RCA, there
      are opportunities to expand beyond the authors' initial approach for using this
      in assessment.

PMID- 30188370
TI  - Do Admissions Multiple Mini-Interview and Traditional Interview Scores Predict
      Subsequent Academic Performance? A Study of Five California Medical Schools.
AB  - PURPOSE: To compare the predictive validities of medical school admissions
      multiple mini-interviews (MMIs) and traditional interviews (TIs). METHOD: This
      longitudinal observational study of 2011-2013 matriculants to five California
      public medical schools examined the associations of MMI scores (two schools) and
      TI scores (three schools) with subsequent academic performance. Regression models
      adjusted for socio-demographics and undergraduate academic metrics examined
      associations of standardized mean MMI and TI scores with United States Medical
      Licensing Examination Step 1 and Step 2 Clinical Knowledge (CK) scores, and, for
      required clerkships, with mean National Board of Medical Examiners Clinical
      Science subject (shelf) exam score and number of honors grades. RESULTS: Of the
      1,460 medical students, 746 (51.1%) interviewed at more than 1 study school; 579
      (39.7%) completed at least 1 MMI and at least 1 TI. Neither interview type was
      associated with Step 1 scores. Higher MMI scores were associated with more
      clerkship honors grades (adjusted incidence rate ratio [AIRR] 1.28 more [95% CI
      1.18, 1.39; P < .01] per SD increase) and higher shelf exam and Step 2 CK scores
      (adjusted mean 0.73 points higher [95% CI 0.28, 1.18; P < .01] and 1.25 points
      higher [95% CI 0.09, 2.41; P = .035], respectively, per SD increase). Higher TI
      scores were associated only with more honors grades (AIRR 1.11 more [95% CI 1.01,
      1.20; P = .03] per SD increase). CONCLUSIONS: MMI scores were more strongly
      associated with subsequent academic performance measures than were TI scores.

PMID- 30188371
TI  - Competing Risks Analysis of Promotion and Attrition in Academic Medicine: A
      National Study of U.S. Medical School Graduates.
AB  - PURPOSE: Competing risk methodology was used to identify variables associated
      with promotion and attrition of newly appointed full-time instructors or
      assistant professors in U.S. LCME-accredited medical schools. METHOD: A national
      sample of U.S. MD-granting medical school graduates in calendar years 1997-2004,
      who received initial full-time instructor or assistant professor appointments
      from January 1, 2000 through December 31, 2012, was followed through December 31,
      2013. Adjusted proportional subdistribution hazard ratios (aSHRs) measured the
      effects of demographic, educational, and institutional variables on promotion and
      attrition. RESULTS: The final study sample included 27,219 full-time instructors
      (n = 10,470) and assistant professors (n = 16,749). In all models (entire sample
      and those stratified by initial rank), faculty who reported all other (vs full
      time faculty) career intentions at graduation and were underrepresented
      racial/ethnic minority (vs white) faculty had lower aSHRs for promotion and
      greater aSHRs for attrition, whereas research-intensive (vs non-research
      intensive) medical school graduates, faculty at schools without a tenure track,
      and mentored K awardees had greater aSHRs for promotion and lower aSHRs for
      attrition. In all models, faculty with >= $100,000 (vs no) debt at graduation had
      greater aSHRs for attrition. Among instructors, women had lower aSHRs for
      attrition than men, but among assistant professors, women had greater aSHRs for
      attrition. CONCLUSIONS: This study adds new knowledge about career trajectories
      of academic medicine faculty initially appointed as full-time instructors. Career
      development interventions and research mentoring during and after medical school
      and debt reduction programs could help increase academic medicine faculty
      retention and promotion.

PMID- 30188372
TI  - Developing Professionalism and Professional Identity through Unproctored,
      Flexible Testing.
AB  - The medical education community has devoted a great deal of attention to the
      development of professionalism in trainees within the context of clinical
      training-particularly regarding trainees' handling of ethical dilemmas related to
      clinical care. The community, however, knows comparatively less about the
      development of professional behavior in medical students during the preclerkship
      years. In medical schools with flexible testing, students take quizzes or
      examinations in an unproctored setting at a time of their choosing-as long as it
      falls within a specified window of time. Unproctored, flexible testing offers
      students early opportunities to develop appropriate professional behavior. In
      this Perspective, the authors outline different flexible testing models from
      three institutions-University of Virginia School of Medicine, University of
      Michigan Medical School, and Icahn School of Medicine at Mount Sinai-all of which
      offer various levels of testing flexibility in relation to time and location. The
      authors' experiences with these models suggests that preclinical medical
      students' early development of professional behavior requires scaffolding by
      faculty and staff. Scaffolding involves setting clear, specific expectations for
      students (often through the form of an honor code), as well as active engagement
      and discussion with learners about the expectations and procedures for self
      regulation of the academic environment.

PMID- 30188373
TI  - The Association Between a Holistic Review in Admissions Workshop and the
      Diversity of Accepted Applicants and Students Matriculating to Medical School.
AB  - PURPOSE: The authors tested for an association between the Association of
      American Medical Colleges' holistic review in admissions (HRA) workshop and the
      compositional diversity of medical school accepted applicants and matriculants in
      schools that held workshops compared to those that did not. METHOD: The authors
      examined school-level data from 134 medical schools accredited by the Liaison
      Committee on Medical Education for the years 2006-2016 using information from the
      American Medical College Application Service. They used a fixed effects
      regression to examine the within-school association between an HRA workshop and
      four measures of diversity: percent first generation college students, percent
      Black/African American, percent Hispanic, and overall level of racial/ethnic
      diversity as measured by a diversity index. RESULTS: For schools that held an HRA
      workshop, descriptive statistics showed higher mean values across all four
      measures of diversity for the post-HRA workshop period (the HRA implementation
      period) compared to the pre-workshop period (accepted applicants: d = .34 to .79;
      matriculants: d = .29 to .73). Analyzing data for all schools, including those
      that did not hold a workshop, regression models showed that the HRA
      implementation period was associated with a significant and sustained increase
      for all four measures of diversity. These finding were consistent for both
      accepted applicants (P < .01) and matriculants (P < .01). CONCLUSIONS: The
      significant increases in all four measures of diversity following an HRA workshop
      support the conclusion that this workshop was associated with increased
      compositional diversity at the participating medical schools.

PMID- 30188374
TI  - Pharmacogenetic and clinical predictors of response to clopidogrel plus aspirin
      after acute coronary syndrome in Egyptians.
AB  - OBJECTIVES: Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel reduces
      the risk for recurrent cardiovascular events after acute coronary syndrome (ACS).
      However, there is significant variation in response to DAPT that may be
      influenced by both genetic and nongenetic factors. This study aimed to assess the
      effect of genetic polymorphisms in PON-1, PEAR-1, P2Y12, CES1, and CYP2C19, along
      with clinical, demographic, and social factors, on variation in response to DAPT
      in Egyptians. PARTICIPANTS AND METHODS: This study included 230 Egyptians treated
      with clopidogrel 75 mg/day and aspirin 81 mg/day for at least 12 months following
      their first ACS. Simple and multivariable logistic regression analyses were
      carried out to identify factors associated with major adverse cardiovascular
      events (MACE), defined as the occurrence of recurrent ACS, ischemic stroke, stent
      related revascularization, or death, in clopidogrel-treated participants.
      RESULTS: Using multivariable logistic regression analysis, the CYP2C19*2
      polymorphism was the only genetic predictor of MACE [odds ratio (OR): 2.23, 95%
      confidence interval (CI): 1.15-4.33, P=0.01]. In addition, proton pump inhibitor
      use (OR: 4.77, 95% CI: 1.47-15.54, P=0.009) and diabetes (OR: 1.83, 95% CI: 1.03
      3.26, P=0.03) were associated with higher cardiovascular risk, whereas statin use
      was associated with lower risk (OR: 0.43, 95% CI: 0.25-0.76, P=0.003). The
      contribution of these four genetic and nongenetic factors explained 19% of the
      variability in risk for MACE in Egyptians treated with DAPT. CONCLUSION: These
      results highlight that CYP2C19*2, along with diabetes, and use of proton pump
      inhibitor and statin are important factors jointly associated with variability in
      clinical response to DAPT following ACS in Egyptians.

PMID- 30188375
TI  - Long-term sleep habits and the risk of breast cancer among Chinese women: a case
      control study.
AB  - Previous observational studies have inconsistently suggested that poor sleep is a
      novel risk factor for breast cancer (BC). However, these studies mainly focused
      on sleep duration; other sleep domains were rarely reported. The aim of this
      study was to evaluate the association of a broad range of sleep domains with the
      risk of BC incidence. We used a community-based 1 : 1 individual matched case
      control design that included 401 female patients with incident BC and 401 age
      matched and area-matched female controls in Jiujiang, China. Long-term sleep
      habits were assessed comprehensively using a validated 17-item Sleep Factors
      Questionnaire. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs)
      were calculated using conditional logistic regression. Light exposure at night
      (highest vs. lowest level, aOR=1.19, 95% CI: 1.06-2.68), habitual timing of sleep
      (after 12 a.m. midnight vs. before 22 p.m., aOR=1.12, 95% CI: 1.03-2.62),
      night/shift work (yes vs. no, aOR=1.38, 95% CI: 1.04-2.71), and frequency of
      night-time wakings (>2 per night vs. never, aOR=1.21, 95% CI: 1.10-2.96) were
      associated with an increased risk of BC after mutually adjusting for other sleep
      parameters. These positive associations remained irrespective of menopausal
      status and tumor estrogen receptor status. There was no association between sleep
      duration, sleep quality, sleep medication use, insomnia frequency, daytime nap,
      and the risk of BC. Our results indicate that sleep problems including light
      exposure at night, night/shift work, late sleeping, and frequent night waking
      could increase the risk of BC development, independent of other sleep factors.

PMID- 30188376
TI  - Physical Activity Among Postoperative Esophageal Cancer Patients.
AB  - BACKGROUND: Previous literature has reported that regular physical activity
      enhances health-related quality of life for cancer patients. However, there is a
      lack of studies that focus on physical activity among postoperative esophageal
      cancer patients. OBJECTIVE: The aims of this study were to (1) describe the
      prevalence of physical activity among postoperative esophageal cancer patients,
      (2) explore variables related to physical activity (demographics, nutrition,
      dysphagia, and health-related qualify of life), and (3) examine potential reasons
      for inactivity among participants who scored low using case studies. METHODS: In
      this cross-sectional design, physical activity was evaluated by the Japanese
      version of the International Physical Activity Questionnaire. Variables were
      analyzed using Spearman rank correlation coefficients, Mann-Whitney U tests, or
      Fisher exact tests. RESULTS: Fifty-eight patients participated in this study; 79%
      met the recommended physical activity guidelines. Present occupational status and
      past leisure-time physical activity behavior before the cancer diagnosis were
      related to current leisure-time physical activity and meeting the guidelines
      postoperatively. Participants who scored 0 (little or no activity) in the
      questionnaire also scored low in health-related quality of life. CONCLUSIONS:
      Participants performed especially well in physical activity related to leisure
      time and transportation. Positive reinforcement is needed for patients who
      perform adequate levels of physical activity, and reviewing the benefits of
      regular physical activity is encouraged for all. IMPLICATIONS FOR PRACTICE:
      Occupational status and past leisure-time physical activity before diagnosis can
      be indicators for promoting physical activity among postoperative esophageal
      cancer patients. Inactive participants should be supported to promote both
      physical activity and health-related qualify of life.

PMID- 30188377
TI  - Reflectance Confocal Microscopy Can Help the Dermatopathologist in the Diagnosis
      of Challenging Skin Lesions.
AB  - Despite the successful assignment of Current Procedural Terminology codes, there
      are barriers to incorporating in vivo reflectance confocal microscopy (RCM) into
      daily practice. Importantly, the dermatopathologist can play a key role in
      interpreting RCM images and can use these images to correlate with
      histopathology. Herein, we describe, using a case series, how RCM can be
      incorporated into the dermatopothalogist's practice. We also summarize the
      criteria for RCM diagnosis of common neoplasms.

PMID- 30188378
TI  - Hypopigmented Interface T-Cell Dyscrasia and Hypopigmented Mycosis Fungoides: A
      Comparative Study.
AB  - Hypopigmented interface T-cell dyscrasia (HITCD) is a distinct form of lymphoid
      dyscrasia that may progress to hypopigmented mycosis fungoides (HMF). We compared
      both diseases as regards their CD4/CD8 phenotype and expression of granzyme B and
      tumor necrosis factor-alpha (TNF-alpha) and how these are affected by narrow-band
      UVB (nb-UVB). The study included 11 patients with HITCD and 9 patients with HMF.
      They received nb-UVB thrice weekly until complete repigmentation or a maximum of
      48 sessions. Pretreatment and posttreatment biopsies were stained using anti CD4,
      CD8, TNF-alpha, and granzyme B monoclonal antibodies. Epidermal lymphocytes were
      CD8 predominant in 54.5% and 66.7% of HITCD and HMF cases, respectively, whereas
      dermal lymphocytes were CD4 predominant in 63.6% and 66.7%, respectively.
      Significantly, more dermal infiltrate was encountered in HMF (P = 0.041). In both
      diseases, granzyme B was only expressed in the dermis, whereas TNF-alpha was
      expressed both in the epidermis and dermis. No difference existed as regards the
      number of sessions needed to achieve repigmentation or cumulative nb-UVB dose
      reached at end of study. (P > 0.05). Narrow-band UVB significantly reduced only
      the epidermal lymphocytes in both diseases (P <= 0.05) with their complete
      disappearance in 8 (72.7%) HITCD and 6 (66.7%) HMF cases. In both diseases, nb
      UVB did not affect granzyme B or TNF-alpha expression (P > 0.05). In conclusion,
      both diseases share the same phenotype, with HITCD being a milder form of T-cell
      dysfunction. In both diseases, epidermal lymphocytes are mainly CD8-exhausted
      cells lacking cytotoxicity, whereas dermal cells are mostly reactive cells
      exerting antitumor cytotoxicity. Tumor necrosis factor-alpha mediates
      hypopigmentation in both diseases and prevents disease progression.
      Repigmentation after nb-UVB in both diseases occurs before and independently from
      disappearance of the dermal infiltrate.

PMID- 30188380
TI  - Maternal Prepregnancy Weight Status and Adolescent Eating Disorder Behaviors. A
      Longitudinal Study of Risk Pathways: Erratum.

PMID- 30188379
TI  - Refractory Hand Dermatitis With Massive Thumb Enlargement.

PMID- 30188382
TI  - The effects of tryptophan enhancement and depletion on plasma catecholamine
      levels in healthy individuals.
AB  - OBJECTIVE: Central nervous system (CNS) serotonin (5-HT) exerts both excitatory
      and inhibitory effects on the sympathetic nervous system (SNS) in animals. In
      this study, we examine the effects of tryptophan enhancement and depletion on
      plasma catecholamine levels in humans. METHODS: The total sample consisted of 164
      healthy men and women who were tested over 2 days. Seventy-nine participants were
      randomized to a tryptophan enhancement condition and eighty-five to a tryptophan
      depletion condition. Both protocols consisted of a "sham-day" followed by an
      "active-day". Blood samples for assessment of plasma norepinephrine and
      epinephrine levels were collected prior and post tryptophan
      enhancement/depletion. Data were analyzed using general linear models. Separate
      analyses were conducted for each study arm and for each measure. RESULTS: In the
      depletion condition, both epinephrine (F(5,330) = 2.69, p = .021) and
      norepinephrine (F(5,335) = 2.79, p =.018) showed small increases on active vs
      'sham' depletion days. There were also significant day X time interactions for
      epinephrine (F(3,171) = 39.32, p < .0001) and norepinephrine (F(3,195) = 31.09, p
      < .0001) levels in the enhancement arm. Tryptophan infusion resulted in a marked
      increase in epinephrine (Premean =23.92+/-12.23 vs. Postmean =81.57+/-62.36) and
      decrease in norepinephrine (Premean =257.2+/-106.11 vs. Postmean =177.04+/-87.15
      ) whereas levels of both catecholamines were stable on the "sham-day".
      CONCLUSIONS: CNS 5-HT exerts both inhibitory and excitatory effects on SNS
      activity in humans, potentially due to stimulation of CNS 5-HT receptors that
      have shown to have inhibitory (5-HT1A) and excitatory (5-HT1A and/or 5-HT2) SNS
      effects in animal models.

PMID- 30188381
TI  - Reporting of Baseline Characteristics to Accompany Analysis by Instrumental
      Variables.
AB  - A property and criticism of instrumental variable (IV) estimators is that they
      estimate the exposure effect in the compliers, individuals whose exposure is
      influenced by the instrument. It is conceivable that the exposure effect is
      different in individuals whose exposure is not influenced by the instrument. For
      that reason, it is useful to know who the compliers are. We present methods for
      reporting averages and other statistics and comparing them between the compliers
      and noncompliers, which are applicable to scenarios in which the instrument and
      exposure are fixed in time and dichotomous. The methods are illustrated in a
      comparison of outcomes between teaching and nonteaching hospitals in patients
      undergoing brain or spinal surgery.

PMID- 30188383
TI  - Cognitive Function 3 and 12 Months After ICU Discharge-A Prospective Cohort
      Study.
AB  - OBJECTIVES: Studies have shown impaired cognitive function after ICU discharge.
      We aimed to describe long-term cognitive function in Danish ICU patients. DESIGN:
      Prospective cohort study. SETTING: Single-center ICU at Zealand University
      Hospital, Koge, Denmark. PATIENTS: Adult patients admitted for over 24 hours.
      INTERVENTION: Three and 12 months after discharge, the patients were visited at
      home and tested with the Repeatable Battery for the Assessment of
      Neuropsychological Status. MEASUREMENTS AND MAIN RESULTS: We included 161
      patients, 79 patients had a 3-month and 53 a 12-month follow-up visit. The
      primary reasons for not being visited at 3-month were death (44 patients),
      decline (26 patients), or transferal to another ICU (6 patients). Visited
      patients were median 67 years old (interquartile range, 59-73), had a median
      Acute Physiology and Chronic Health Evaluation score of 20 (interquartile range,
      16-26), 58% were on a ventilator, and 30% were surgical patients. The mean
      Repeatable Battery for the Assessment of Neuropsychological Status score was 67
      (SD, 21), compared with a normal value of 100 (15). A total of 57% had Repeatable
      Battery for the Assessment of Neuropsychological Status scores corresponding to
      moderate traumatic brain injury, 46% scored corresponding to light Alzheimer's
      disease, and 73% corresponding to mild cognitive impairment. After 12 months, the
      Repeatable Battery for the Assessment of Neuropsychological Status was still
      reduced (71 [25]). We examined protective and risk factors using multiple linear
      regression and found protective effects of being employed before admission (p =
      0.0005) or being admitted from a surgical ward (p = 0.019). CONCLUSIONS: In this
      prospective cohort study of Danish ICU patients, we found significantly reduced
      cognitive function for intensive care patients 3 and 12 months after discharge.

PMID- 30188384
TI  - Seizure Identification by Critical Care Providers Using Quantitative
      Electroencephalography.
AB  - OBJECTIVES: To compare the performance of critical care providers with that of
      electroencephalography experts in identifying seizures using quantitative
      electroencephalography display tools. DESIGN: Diagnostic accuracy comparison
      among healthcare provider groups. SETTING: Multispecialty quaternary children's
      hospital in Canada. SUBJECTS: ICU fellows, ICU nurses, neurophysiologists, and
      electroencephalography technologists. INTERVENTION: Two-hour standardized one-on
      one training, followed by a supervised individual review of 27 continuous
      electroencephalography recordings with the task of identifying individual
      seizures on eight-channel amplitude-integrated electroencephalography and color
      density spectral array displays. MEASUREMENTS AND MAIN RESULTS: Each participant
      reviewed 27 continuous electroencephalograms comprising 487 hours of recording
      containing a total of 553 seizures. Performance for seizure identification was
      compared among groups using a nested model analysis with adjustment for
      interparticipant variability within groups and collinearity among recordings.
      Using amplitude-integrated electroencephalography, sensitivity for seizure
      identification was comparable among ICU fellows (83.8%), ICU nurses (73.1%), and
      neurophysiologists (81.5%) but lower among electroencephalographic technologists
      (66.7%) (p = 0.003). Using color density spectral array, sensitivity was
      comparable among ICU fellows (82.4%), ICU nurses (88.2%), neurophysiologists
      (83.3%), and electroencephalographic technologists (73.3%) (p = 0.09). Daily
      false-positive rates were also comparable among ICU fellows (2.8 for amplitude
      integrated electroencephalography, 7.7 for color density spectral array), ICU
      nurses (4.2, 7.1), neurophysiologists (1.2, 1.5), and electroencephalographic
      technologists (0, 0) (p = 0.41 for amplitude-integrated electroencephalography; p
      = 0.13 for color density spectral array). However, performance varied greatly
      across individual electroencephalogram recordings. Professional background
      generally played a greater role in determining performance than individual skill
      or electroencephalogram recording characteristics. CONCLUSIONS: Following
      standardized training, critical care providers and electroencephalography experts
      displayed similar performance for identifying individual seizures using both
      amplitude-integrated electroencephalography and color density spectral array
      displays. Although these quantitative electroencephalographic trends show promise
      as a tool for bedside seizure screening by critical care providers, these
      findings require confirmation in a real-world ICU environment and in daily
      clinical use.

PMID- 30188386
TI  - Benefits and risk management of functional foods in the context of chronic
      diseases.

PMID- 30188385
TI  - Enhanced cognitive behavioural therapy for patients with eating disorders: a
      systematic review.
AB  - PURPOSE OF REVIEW: The aim of this study was to provide an update of the most
      recent (since January 2014) enhanced cognitive behavioural therapy (CBT-E)
      effectiveness studies (randomized controlled trials and open trials) on bulimia
      nervosa, binge eating disorder and transdiagnostic samples. RECENT FINDINGS: Out
      of 451 screened studies, seven effectiveness studies (five randomized and two
      open trials) were included in this review: of these, three had a bulimia nervosa
      sample and four a transdiagnostic sample (all conducted in an outpatient
      setting). Substantial differences in posttreatment remission rates were found
      (range: 22.2-67.6%) due, in part, to differences in samples and
      operationalization of clinical significant change. SUMMARY: There is robust
      evidence that CBT-E is an effective treatment for patients with an eating
      disorder. However, more studies on differential effects and working mechanisms
      are required to establish the specificity of CBT-E.

PMID- 30188387
TI  - Point-of-care ultrasound in end-stage kidney disease: beyond lung ultrasound.
AB  - PURPOSE OF REVIEW: Following the miniaturization of ultrasound devices, point-of
      care ultrasound (POCUS) has been proposed as a tool to enhance the value of
      physical examination in various clinical settings. The objective of this review
      is to describe the potential applications of POCUS in end-stage renal disease
      patients (ESRD). RECENT FINDINGS: With basic training, the clinician can perform
      pulmonary, vascular, cardiac, and abdominal POCUS at the bedside of ESRD
      patients. Pulmonary ultrasound can be used to quantify pulmonary congestion and
      for the differential diagnosis of dyspnea. Ultrasound of the inferior vena cava
      combined with simple cardiac ultrasound can be used to promptly investigate the
      mechanism of hemodynamic instability. Vascular ultrasound can be used for
      troubleshooting of arteriovenous fistula problems and for catheter installation.
      Multiple potential applications of POCUS in the ESRD population are reviewed,
      including areas of future research. SUMMARY: Acquiring basic skills in POCUS may
      improve patient care through the rapid identification of threats, improved
      diagnostic abilities for common symptoms, and safer procedures. The adoption of
      POCUS in undergraduate, internal medicine and nephrology training curriculums
      will likely lead to a gradual introduction of this technology in the care of ESRD
      patients.

PMID- 30188388
TI  - Context for Practice: Polyhexamethylene Biguanide and Wound Care: Cutting-Edge
      Evidence.

PMID- 30188389
TI  - Gibson DJ. An Ex Vivo Comparison of 2 Cyanoacrylate Skin Protectants. Journal of
      Wound, Ostomy and Continence Nursing 2018;45(1): 31-36.

PMID- 30188390
TI  - Author's response to Letter to the Editor Re: Gibson DJ. An Ex Vivo Comparison of
      2 Cyanoacrylate Skin Protectants. Journal of Wound, Ostomy and Continence
      Nursing. 2018;45(1):31-36.

PMID- 30188391
TI  - Pressure Injury Education in the Department of Veterans Affairs: Results of a
      National Wound Provider Cross-sectional Survey.
AB  - PURPOSE: The aim of this study was to describe experience, training, educational
      needs and preferences, and perceptions of pressure injury (PI) prevention
      education of wound care providers in the Veterans Health Administration (VHA) of
      the Department of Veterans Affairs (VA) as an indicator of effectiveness of the
      mandated VHA PI Prevention Program. SUBJECTS AND SETTING: A convenience sample of
      national VHA wound care providers practicing in VHA facilities was compiled from
      members of special interest groups and committees and by referrals from known
      wound care specialists and clinicians (N = 1726). The response rate was 24% (n =
      410). DESIGN: Cross-sectional, descriptive study. METHODS: A 42-item online cross
      sectional survey was administered via a blast-email of the survey link to the
      sample. The survey link was active for 1 month (March 3-31, 2014). The survey
      queried demographic data, PI experience and education, and their perceptions and
      preferences for PI education. Quantitative responses underwent descriptive
      analyses, and responses to open-ended questions were analyzed by content
      analysis. RESULTS: The majority of the 415 respondents completed most of the
      questionnaire (n = 310, 74%). Half were board-certified providers with a mean
      wound care experience of 14.2 years (standard deviation = 9.8 years). Preference
      for type of wound training ranged from 17% for online gaming to 82% for face-to
      face training. Training provided by facilities was perceived to be inadequate for
      wound care by 60% (n = 175) and inadequate for PI care by 49% (n = 142).
      CONCLUSIONS: The 2 greatest areas of need in PI care identified by wound care
      providers were education and documentation. These same issues were identified as
      problematic by an audit of PI prevention and management at 47 VHA facilities that
      was conducted by the VA Office of Inspector General.

PMID- 30188392
TI  - Changes in Peristomal Skin Condition and User Experience of a Novel Ostomy
      Barrier Ring With Assisted Flow: A 6-Week Feasibility Study.
AB  - PURPOSE: This purpose of this study was to evaluate a novel barrier ring with an
      assisted flow mechanism by assessing changes in peristomal moisture-associated
      skin damage (MASD) and perceptions of comfort, security, handling, and discretion
      in persons with an ileostomy for 6 months or longer. DESIGN: Single-arm, open
      labeled feasibility study. SUBJECTS AND SETTINGS: Twenty participants (aged >=18
      years) with an ileostomy for 6 months or more participated in the study and 12
      completed data collection. The primary reason for dropouts concerned
      compatibility issues with the barrier ring when used with certain convex pouching
      systems. METHODS: Participants used the barrier ring along with their normal
      ostomy pouching system for a period of 6 weeks. Changes in skin condition were
      assessed using the Ostomy Skin Tool (OST). Participants' perception of the
      barrier rings' comfort, security, handling, and discretion were also recorded on
      a 10-point scale, where participants would offer a low score if their experience
      was negative and a higher score if their experience was positive. Participants
      changed pouches and barrier rings at their own discretion. For participants who
      completed the study, the average skin condition and median ratings of comfort,
      security, handling, and discretion at 6 weeks were compared to baseline values.
      RESULTS: Twelve of the 20 participants (60%) completed the study. For those who
      completed, the mean score on the OST decreased from 6.2 +/- 1.90 (mean +/- SD) at
      baseline to 3.4 +/-1.73 at 6 weeks, indicating a mean reduction of 2.8 (95% CI, 
      1.6 to -3.9; P < .001). The peristomal skin condition of 9 participants improved,
      whereas 3 experienced no change. All participants who completed the study rated
      comfort, handling, security, and discretion highly (median score 10 at baseline
      and at 6 weeks). CONCLUSIONS: Study findings indicate the novel ostomy barrier
      ring may reduce levels of peristomal MASD in persons living with an ileostomy,
      though a more extensive trial with a control group is recommended.

PMID- 30188393
TI  - Evaluation of Validity and Reliability of a Revised Incontinence-Associated Skin
      Damage Severity Instrument (IASD.D.2) by 3 Groups of Nursing Staff.
AB  - PURPOSE: The purpose of this study was to evaluate a revised version of the
      Incontinence-Associated Skin Damage Severity instrument (IASD.D.2) using 3
      different groups of nursing staff. Revisions to the instrument included
      renumbering 1 body area where incontinence-associated dermatitis (IAD) occurs
      into 2 areas (right and left), which raised the total possible score from 52 to
      56, and defining the borders of the body areas. DESIGN: Observational, evaluative
      design. SAMPLE AND SETTING: Five clinical experts certified in wound, ostomy,
      and/or continence (WOC) nursing evaluated content validity. Evaluators were
      attendees at the WOC Nurses (WOCN) Society 2014 conference, hospital nurses, and
      nursing staff at a nursing home. Evaluators were attendees at the WOCN Society's
      2014 National Conference, hospital nurses at a community hospital with Magnet
      designation, and nursing staff at a skilled nursing home in the Midwestern United
      States. The evaluator group comprised 198 conference attendees (all nurses; age
      53 +/- 8.2 years, mean +/- SD), 67 hospital nurses (age 37 +/- 11 years), and 34
      nursing home nursing staff (age 45 +/-13.8 years). The majority of evaluators
      (>75%) in each of the groups were female. METHODS: Clinical experts evaluated the
      content validity of the revised instrument. Evaluators scored 5 to 9 photographic
      cases using the revised instrument. Four of the cases were scored by all
      evaluators. The agreement of case scores among all evaluators was analyzed to
      assess interrater reliability. The scores of evaluators grouped by evaluators'
      self-identified skin color or nursing experience (<10 years vs >=10 years) were
      also tested for differences. To provide evidence for criterion validity, the
      agreement of evaluators' scores with experts' scores (considered a "gold
      standard" in this study) was analyzed. RESULTS: The agreement of the IASD.D.2
      scores among all evaluators within each group ranged from 0.74 to 0.79,
      suggesting good interrater reliability. The agreement of each group of evaluators
      with the experts for all case scores ranged from 0.82 to 0.85, suggesting good
      criterion validity. There was no significant difference in scores by evaluators'
      skin color or nursing experience. CONCLUSION: The revised IASD.D.2 has good
      content and criterion validity and interrater reliability. The instrument has
      potential to standardize reporting of IAD severity in research and clinical
      practice and assist communication about IAD among nursing staff.

PMID- 30188394
TI  - Rationale and Design of a Novel Method to Assess the Usability of Body-Worn
      Absorbent Incontinence Care Products by Caregivers.
AB  - PURPOSE: The purpose of this study was to develop and test a new method to
      measure the usability of absorbent incontinence care products from the
      caregivers' perspective and to investigate if the method can be used to
      differentiate between product types in a product change. DESIGN: Process
      evaluation and validation study. SUBJECTS AND SETTING: Product developers and end
      users participated in designing the new method. Thereafter, professional
      caregivers acted as testers of the new method, ranking usability when performing
      absorbent product changes on patients in a simulated nursing home care
      environment, assisted by third-party research institute moderators. METHODS:
      Design and evaluation of a new method designed to assess the usability of body
      worn absorbent incontinence care products for lay caregivers were completed. The
      evaluation included formative and summative evaluations of effectiveness (product
      fit), efficiency (time and physical workload), and satisfaction. A person
      centered approach aimed at including all subjects and settings to generate a
      single usability score for decision making and product benchmarking. Experienced
      caregivers changed 4 types of products: (1) disposable body-worn pads with mesh
      briefs (2-piece system); (2) disposable all-in-one briefs; (3) disposable, T
      shaped, and belted brief; and (4) disposable pull-up pants on simulated patients
      in standing or lying position. Each product change was performed by 1 unassisted
      experienced caregiver. The probability of success as a score for each product
      type was calculated across the 4 metrics and reported with 95% confidence
      intervals (CIs). Descriptive and inferential statistics were developed assuming a
      binary statistical model, using the weighted scores from each of the factors. An
      overall usability score was calculated. RESULTS: The method we developed
      discriminated between usability of different product types. The overall score for
      the disposable pull-up product (90%; CI: 83%-97%) was better (P < .05) than for
      the disposable T-shaped brief (83%; CI: 77%-89%), the disposable brief (53%; CI:
      45%-61%), and the disposable body-worn pad with mesh pant (61%; CI: 56%-66%) in
      standing patients. For lying patients, the overall score for the disposable T
      shaped brief product (81%; CI: 73%-89% was better (P < .05) than the disposable
      brief (65%; CI: 45%-61%) and the disposable body-worn pads with mesh brief (62%;
      CI: 55%-69%). Reliability was evaluated quantitatively in terms of measurement
      uncertainties in the results. CONCLUSION: The method we described demonstrated
      differentiation of usability based on product type indicating concurrent
      validity. Further testing in diverse real-world care environments is needed to
      evaluate and confirm the validity and to assess reliability of this method in the
      research setting.

PMID- 30188395
TI  - Advanced Techniques in the Use of Negative Pressure Wound Therapy for Closure of
      Complex Neonatal Abdominal Wounds.
AB  - BACKGROUND: Negative pressure wound therapy (NPWT) has been described for closure
      of complex neonatal abdominal wounds, but advanced techniques for stoma or
      fistula control, skin protection, and the use of high pressure therapy not as
      well established. CASES: We identified neonatal patients at our institution who
      received NPWT for a complex abdominal wound, defined as a wound associated with a
      stoma or fistula with partial or complete dehiscence of the abdominal fascia or
      skin. We then reviewed techniques for decreasing wound contamination and
      protecting the newborn's skin. One patient had an especially complex wound; she
      was born at ~23 weeks' gestational age (birth weight 580 g). She developed
      necrotizing enterocolitis and strictures, requiring multiple surgeries to relieve
      obstruction, ultimately resulting in an end ileostomy with mucous fistula. She
      suffered from wound dehiscence and retraction of her surgically created stoma,
      resulting in a complex abdominal wound with significant damage to the surrounding
      skin. We used advanced NPWT techniques to heal her wound, including topical skin
      protectants, placement of an adhesive dressing over the skin prior to placement
      of negative pressure dressing, placement of a negative pressure sponge directly
      on the wound bed and stoma, diversion of enteric contents away from the wound
      using a Malecot catheter, and an increase in the negative pressure applied.
      CONCLUSION: Complex neonatal abdominal wounds can be treated effectively using
      NPWT. The techniques we describe divert enteric contents away from the wound bed
      while maintaining negative pressure and protecting the surrounding skin. In
      addition, we used negative pressure up to -125 mm Hg and found it was well
      tolerated by our patients.

PMID- 30188397
TI  - Getting Ready for Wound Certification: Assessment and Management of Atypical
      Wounds.

PMID- 30188396
TI  - Advocating for Canadians Living With an Ostomy and the Federal Disability Tax
      Credit.

PMID- 30188398
TI  - WOCN(r)-Accredited Professional Education Programs.

PMID- 30188399
TI  - Pancreatectomy With Arterial Resection for Pancreatic Adenocarcinoma: How Can It
      Be Done Safely and With Which Outcomes?: A Single Institution's Experience With
      118 Patients.
AB  - OBJECTIVE: This study assesses the safety and outcomes of the largest cohort of
      pancreatectomy with arterial resection (P-AR). BACKGROUND: A high postoperative
      mortality rate and uncertain oncologic benefits have limited the use of P-AR for
      locally advanced pancreatic adenocarcinoma. METHODS: We retrospectively reviewed
      a prospectively maintained database of patients who underwent P-AR between
      January 1990 and November 2017. Univariate and multivariate Cox analyses were
      used to assess prognostic factors for survival. RESULTS: There were 118
      consecutive resections (51 pancreaticoduodenectomies, 18 total pancreatectomies,
      and 49 distal splenopancreatectomies). Resected arterial segments included the
      coeliac trunk (50), hepatic artery (29), superior mesenteric artery (35), and
      other segments (4). The overall mortality and morbidity were 5.1% and 41.5%,
      respectively. There were 84 (75.4%) patients who received neoadjuvant
      chemotherapy, 105 (89%) simultaneous venous resections, and 101 (85.5%) arterial
      reconstructions. The rates of R0 resection and pathologic invasion of venous and
      arterial walls were 52.4%, 74.2%, and 58%, respectively. The overall survival was
      59%, 13%, and 11.8% at 1, 3, and 5 years, respectively. The median overall
      survival after resection was 13.70 months (CI 95%:11-18.5 mo). In multivariate
      analysis, R0 resection (HR: 0.60; 95% CI: 0.38-0.96; P = 0.01) and venous
      invasion (HR: 1.67; 95% CI: 1.01-2.63; P = 0.04) were independent prognostic
      factors. CONCLUSION: In a specialized setting, P-AR for locally advanced
      pancreatic adenocarcinoma can be performed safely with limited mortality and
      morbidity. Negative resection margin and the absence of associated venous
      invasion might predict favorable long-term outcomes.

PMID- 30188400
TI  - A Comparative Analysis of Survival and Funding Discrepancies in Cancers with High
      Mortality.
AB  - OBJECTIVE: Comparative analyses of survival and funding statistics in cancers
      with high mortality were performed to quantify discrepancies and identify areas
      for intervention. BACKGROUND: Discrepancies in research funding may contribute to
      stagnant survival rates in pancreatic ductal adenocarcinoma (PDAC). METHODS: The
      Surveillance, Epidemiology, and End Results database was queried for survival
      statistics. Funding data were obtained from the National Cancer Institute (NCI).
      Clinical trial data were obtained from www.clinicaltrials.gov. Cancers with high
      mortality were included for analyses. RESULTS: Since 1997, PDAC has received
      lesser funding ($1.41 billion) than other cancers such as breast ($10.52
      billion), prostate ($4.93 billion), lung ($4.80 billion), and colorectal ($4.50
      billion). Similarly, fewer clinical trials have been completed in PDAC (n = 608)
      compared with breast (n = 1904), lung (n = 1629), colorectal (n = 1080), and
      prostate (n = 1055) cancer. Despite this, since 1997, dollars invested in PDAC
      research produced a greater return on investment with regards to 5-year overall
      survival (5Y-OS) compared with breast, prostate, uterine, and ovarian cancer.
      Incremental cost-effectiveness analysis demonstrates that millions (liver, non
      Hodgkin lymphoma, and melanoma) and billions (colorectal and lung) of dollars
      were required for each additional 1% increase in 5Y-OS compared with PDAC.
      Funding of research towards early diagnosis of PDAC has decreased by 19% since
      2007. For nearly all cancers, treatment-related research receives the highest
      percentage of NCI funding. CONCLUSIONS: Funding of PDAC research is significantly
      less than other cancers, despite its higher mortality and greater potential to
      improve 5Y-OS. Increased awareness and lobbying are required to increase funding,
      promote research, and improve survival.

PMID- 30188401
TI  - Association of Patient-reported Experiences and Surgical Outcomes Among Group
      Practices: Retrospective Cohort Study.
AB  - OBJECTIVE: The aim of the study was to determine the association of patient
      reported experiences (PREs) and risk-adjusted surgical outcomes among group
      practices. BACKGROUND: The Centers for Medicare and Medicaid Services required
      large group practices to submit PREs data for successful participation in the
      Physician Quality Reporting System (PQRS) using the Consumer Assessment of
      Healthcare Providers and Systems for PQRS survey. Whether these PREs data
      correlate with perioperative outcomes remains ill defined. METHODS: Operations
      between January 1, 2014 and December 31, 2016 in the American College of
      Surgeons' National Surgical Quality Improvement Program registry were merged with
      2015 Consumer Assessment of Healthcare Providers and Systems for PQRS survey
      data. Hierarchical logistic models were constructed to estimate associations
      between 7 subscales and 1 composite score of PREs and 30-day morbidity, unplanned
      readmission, and unplanned reoperation, separately, while adjusting for patient-
      and procedure mix. RESULTS: Among 328 group practices identified, patients
      reported their experiences with clinician communication the highest (mean +/-
      standard deviation, 82.66 +/- 3.10), and with attention to medication cost the
      lowest (25.96 +/- 5.14). The mean composite score was 61.08 (+/-6.66). On
      multivariable analyses, better PREs scores regarding medication cost, between
      visit communication, and the composite score of experience were each associated
      with 4% decreased odds of morbidity [odds ratio (OR) 0.96, 95% confidence
      interval (CI) 0.92-0.99], readmission (OR 0.96, 95% CI 0.93-0.99), and
      reoperation (OR 0.96, 95% CI 0.93-0.99), respectively. In sensitivity analyses,
      better between-visit communication remained significantly associated with fewer
      readmissions. CONCLUSIONS: In these data, patients' report of better between
      visit communication was associated with fewer readmissions. More sensitive,
      surgery-specific PRE assessments may reveal additional unique insights for
      improving the quality of surgical care.

PMID- 30188403
TI  - Further to the Right: Piggyback Anastomosis on the Right Hepatic Vein Facilitates
      the Implantation of Small Liver Grafts (The 1-vein Technique).

PMID- 30188402
TI  - Guideline Assessment Project: Filling the GAP in Surgical Guidelines: Quality
      Improvement Initiative by an International Working Group.
AB  - OBJECTIVE: The aim of the study was to identify clinical practice guidelines
      published by surgical scientific organizations, assess their quality, and
      investigate the association between defined factors and quality. The ultimate
      objective was to develop a framework to improve the quality of surgical
      guidelines. SUMMARY BACKGROUND DATA: Evidence on the quality of surgical
      guidelines is lacking. METHODS: We searched MEDLINE for clinical practice
      guidelines published by surgical scientific organizations with an international
      scope between 2008 and 2017. We investigated the association between the
      following factors and guideline quality, as assessed using the AGREE II
      instrument: number of guidelines published within the study period by a
      scientific organization, the presence of a guidelines committee, applying the
      GRADE methodology, consensus project design, and the presence of intersociety
      collaboration. RESULTS: Ten surgical scientific organizations developed 67
      guidelines over the study period. The median overall score using AGREE II tool
      was 4 out of a maximum of 7, whereas 27 (40%) guidelines were not considered
      suitable for use. Guidelines produced by a scientific organization with an output
      of >=9 guidelines over the study period [odds ratio (OR) 3.79, 95% confidence
      interval (CI), 1.01-12.66, P = 0.048], the presence of a guidelines committee (OR
      4.15, 95% CI, 1.47-11.77, P = 0.007), and applying the GRADE methodology (OR
      8.17, 95% CI, 2.54-26.29, P < 0.0001) were associated with higher odds of being
      recommended for use. CONCLUSIONS: Development by a guidelines committee, routine
      guideline output, and adhering to the GRADE methodology were found to be
      associated with higher guideline quality in the field of surgery.

PMID- 30188404
TI  - 90-90-90 HIV targets: implications for HIV-associated tuberculosis.
AB  - PURPOSE OF REVIEW: The HIV and Mycobacterium tuberculosis syndemic remains a
      major global public health threat. HIV and tuberculosis (TB) global targets have
      been set. Success will depend on achieving combined disease control. We explore
      current policy, economic investment, and disease control strategies for HIV, TB,
      and HIV-associated TB. We review published HIV, TB, and HIV-associated TB data
      for 30 WHO priority countries and propose a comprehensive HIV and TB care
      continua. RECENT FINDINGS: In 2016, people living with HIV (PLHIV) on
      antiretroviral treatment (ART) ranged from 13 to 84%; viral suppression ranged
      from 21 to 79%. Only 5% of PLHIV without TB reported a course of isoniazid
      preventive therapy (IPT). TB treatment success (2015) ranged from 34 to 94%. Data
      for the combined indicators: TB treatment success and viral suppression and IPT
      and ART for PLHIV are not collected. Reported 2003-2017 global international and
      domestic resources for TB and HIV-associated TB averaged $2.9 billion per year;
      cumulative total was $43 billion. SUMMARY: Integrating HIV and TB control efforts
      including monitoring and evaluation systems will be necessary to end both TB and
      HIV. A comprehensive HIV and TB continuum supports integrated, comprehensive HIV
      and TB disease control efforts focused on improving both individual and public
      health.

PMID- 30188405
TI  - Neurological and Ophthalmological Manifestations of Varicella Zoster Virus.
AB  - BACKGROUND: Approximately 1 million new cases of herpes zoster (HZ) occur in the
      United States annually, including 10%-20% with herpes zoster ophthalmicus (HZO).
      Postherpetic neuralgia, a debilitating pain syndrome occurs in 30% HZ, whereas
      50% HZO develop ophthalmic complications. Diplopia from cranial nerve palsy
      occurs in less than 30% HZO, whereas optic neuropathy is seen in less than 1%
      HZO. We reviewed recent developments in the diagnosis, treatment, and prevention
      of HZ as well as neurological and ophthalmological complications of relevance to
      the neuro-ophthalmologist. EVIDENCE ACQUISITION: We searched the English language
      literature on Pubmed and Google scholar for articles relevant to the various
      sections of this review. RESULTS: Antiviral treatment should be initiated within
      48-72 hours of onset of HZ and HZO to decrease pain and reduce complications. We
      recommend neuroimaging in all patients with neuro-ophthalmic manifestations such
      as diplopia and acute vision loss. Diagnostic confirmation using polymerase chain
      reaction and serology on paired serum and cerebrospinal fluid samples should be
      obtained in those with neurological signs and symptoms or abnormal imaging.
      Patients with neurological and/or retinal varicella zoster virus (VZV) infection
      should be treated promptly with intravenous acyclovir. Patients with isolated
      optic neuropathy or cranial nerve palsy can be managed with oral antivirals. The
      prognosis for visual recovery is good for patients with isolated optic neuropathy
      and excellent for patients with isolated ocular motor cranial nerve palsy.
      CONCLUSIONS: HZ produces a spectrum of potentially blinding and life-threatening
      complications that adversely affect quality of life and increase health care
      costs. Individuals at risk for HZ, such as the elderly and immunocompromised,
      should be encouraged to receive the highly effective VZV vaccine to prevent HZ
      and its complications.

PMID- 30188406
TI  - Reproducing the human mucosal environment ex vivo: inflammatory bowel disease as
      a paradigm.
AB  - PURPOSE OF REVIEW: The medical management of inflammatory bowel disease (IBD)
      remains problematic with a pressing need for innovation in drug development as
      well as delivery of personalized therapies. Both the disease's inherent
      pathophysiologic complexity and heterogeneity in its etiology conspire in making
      it difficult to accurately model for either the purposes of basic research or
      drug development. Multiple attempts at creating meaningful experimental models
      have fallen short of adequately recapitulating the disease and most do not
      capture any aspect of the cause or the effects of patient heterogeneity that
      underlays most of the difficulties faced by physicians and their patients. In
      vivo animal models, tissue culture systems, and more recent synthetic biology
      approaches are all too simplistically reductionist for the task. However, ex vivo
      culture platforms utilizing patient biopsies offer a system that more closely
      mimics end-stage disease processes that can be studied in detail and subjected to
      experimental manipulations. RECENT FINDINGS: Recent studies describe further
      optimization of mucosal explant cultures in order to increase tissue viability
      and maintain a polarized epithelial layer. Current applications of the platform
      include studies of the interplay between the epithelial, immune and stromal
      compartment of the intestinal tissue, investigation of host-microbial
      interactions, preclinical evaluation of candidate drugs and uncovering mechanisms
      of action of established or emerging treatments for IBD. SUMMARY: Patient explant
      based assays offer an advanced biological system in IBD that recapitulates
      disease complexity and reflects the heterogeneity of the patient population. In
      its current stage of development, the system can be utilized for drug testing
      prior to the costlier and time-consuming evaluation by clinical trials. Further
      refinement of the technology and establishment of assay readouts that correlate
      with therapeutic outcomes will yield a powerful tool for personalized medicine
      approaches in which individual patient responses to available treatments are
      assessed a priori, thus reducing the need for trial and error within the clinical
      setting.

PMID- 30188407
TI  - Endoscopic treatment of pain in chronic pancreatitis.
AB  - PURPOSE OF REVIEW: Pain is the most common symptom of chronic pancreatitis,
      having a profound effect on patients and a broad socioeconomic impact. Endoscopy
      is guideline recommended as first-line management for chronic pancreatitis pain
      in certain clinical scenarios. Herein, we provide an evidence-based review of the
      endoscopic treatment of pain due to chronic pancreatitis while highlighting some
      important confounders in the measurement of this outcome in clinical practice and
      research. RECENT FINDINGS: Multiple recent studies have reported on the efficacy
      of current endoscopic therapies for chronic pancreatitis pain. Despite the high
      technical success rates of these procedures, pain outcomes remain disappointing.
      Complex mechanisms beyond ductal hypertension, such as central sensitization,
      visceral hypersensitivity and inflammatory neuritis account for some of the
      discordance observed between the rates of technical and clinical success. In
      addition, the sham effect is increasingly recognized as a confounder when
      interpreting the procedural benefit. Nevertheless, there are multiple promising
      innovations in the field of pancreatic endoscopy that are aimed to improve
      technical and clinical outcomes, but rigorous investigation is necessary to
      establish their role in clinical practice. SUMMARY: Endoscopic therapy for
      chronic pancreatitis pain appears to be safe and effective in certain contexts
      and recent innovations in the field will hopefully further improve outcomes. In
      addition to evaluating the technical success of endotherapy in chronic
      pancreatitis, methodologically rigorous research focusing on patient-centered
      outcomes and accounting for the sham effect is necessary to advance this field.

PMID- 30188408
TI  - A prediction model for successful anticoagulation in cirrhotic portal vein
      thrombosis.
AB  - BACKGROUND AND OBJECTIVE: Portal vein thrombosis (PVT) is a common complication
      in cirrhosis, and when complete, it increases morbidity and mortality in liver
      transplant candidates. The aim of the study was to assess the hemostatic status,
      as well as clinical characteristics of thrombus and patients, as predictors of
      therapeutic efficacy of anticoagulation for the treatment of PVT in cirrhotics.
      PATIENTS AND METHODS: Patients with cirrhosis consecutively treated for PVT with
      enoxaparin were enrolled. All patients underwent evaluation of coagulation status
      and thrombophilia screening. Thrombus characteristics and extension were
      evaluated at baseline and during follow-up. Anticoagulation was continued until
      recanalization or up to 12 months. Variables correlated with the response to
      anticoagulation were used to create a predictive score that was validated in an
      external multicenter cohort. RESULTS: A total of 65 patients were included and
      had partial PVT in most cases (72%). Treatment with enoxaparin resulted in an
      overall response rate of 66% (43/65) after a median time of 4.4 months and 76%
      (33/43) within the first 6 months. At multivariate analysis, efficacy of
      anticoagulation correlated with the severity of liver disease, complete verus
      partial PVT, age of the thrombus, and time interval from treatment start (<6
      months). The areas under the curve of the statistical model for predicting the
      response to anticoagulation were 0.84 and 0.76 for the training (n=65) and
      validation (n=60) cohorts, respectively. CONCLUSION: Early diagnosis and early
      treatment are key factors for the successful management of PVT in cirrhosis, so
      that screening of PVT and prompt start of anticoagulant treatment should be
      mandatory.

PMID- 30188409
TI  - Meta-analysis indicates that add-on devices and new endoscopes reduce colonoscopy
      adenoma miss rate.
AB  - INTRODUCTION: A variety of add-on devices and new-generation endoscopes have the
      potential to detect lesions 'hidden' behind colonic folds. We measured the effect
      of these new modalities on colonoscopy's lesions miss rates by a meta-analysis of
      data from individual studies. MATERIALS AND METHODS: We performed literature
      searches in Medline and Cochrane Library for back-to-back randomized-controlled
      trials evaluating colonoscope add-on devices and new endoscopes in terms of
      lesions miss rates. The effect size on study outcomes is shown as relative risk
      (95% confidence interval). RESULTS: We identified nine tandem studies with 1594
      patients: seven evaluating add-on devices (one with cap, two with Endocuff, one
      with Endorings, one with Third-Eye Retroscope, two with G-EYE endoscope) and two
      evaluating the full-spectrum endoscopy system (FUSE) in comparison with
      conventional colonoscopy (CC). Overall, adenoma miss rate (AMR) was significantly
      lower with add-on devices/FUSE [0.33 (0.22-0.50), P<0.00001] compared with CC,
      the effect being similar among the add-on devices [0.35 (0.22-0.57), P<0.0001]
      and the FUSE [0.26 (0.15-0.46), P<0.00001] studies, respectively. Advanced AMR
      and polyp miss rate (PMR) were also significantly lower using add-on devices/FUSE
      [0.30 (0.21-0.44), P<0.0001 and 0.31 (0.13-0.79), P=0.01, respectively]. Use of
      add-on devices/FUSE scope was associated with significantly lower AMR and PMR in
      the proximal colon and it was associated with shortening of the colonoscopy
      surveillance interval. CONCLUSION: Our meta-analysis provides evidence that AMR,
      advanced AMR, and PMR are significantly lower using add-on to colonoscope devices
      and the full-spectrum endoscopy systems compared with CC. Heterogeneity among the
      included studies and the small number of detected advanced adenomas call for
      cautious interpretation of the results.

PMID- 30188410
TI  - Intracranial hypertension: a current review.
AB  - PURPOSE OF REVIEW: To provide a current review of recent publications with
      regards to intracranial hypertension. RECENT FINDINGS: Attempts were made to
      provide pediatric data; however, the recent completion of the Idiopathic
      Intracranial Hypertension Treatment Trial (IIHTT) has provided a wealth of data
      with regards to adult intracranial hypertension.The pediatric incidence of
      intracranial hypertension ranges between 0.63 and 0.71 per 100 000 children. A
      majority of pediatric cases responded to acetazolamide, with resolution of
      headache averaging 3.8 weeks. Most patients require less than 1 year of treatment
      with male sex, older age at diagnosis, primary intracranial hypertension, and
      lack of headache being predictors of good response. Fluorescein angiography has
      the highest accuracy in distinguishing true papilledema from pseudopapilledema.
      The IIHTT found Frisen grade of papilledema was within 1 grade in 92.8% of
      patients. Monitoring of potassium levels is not required and aplastic anemia was
      not seen in patients taking acetazolamide. SUMMARY: Although the newer pediatric
      studies report incidence rates in pediatric intracranial hypertension are lower
      than seen in adults, intracranial hypertension is still a concern in pediatrics.
      There has been a wealth of information with regards to symptomatology, treatment,
      and outcomes from the IIHTT that will hopefully assist with management in the
      pediatric population.

PMID- 30188411
TI  - Posttraumatic headache in pediatrics: an update and review.
AB  - PURPOSE OF REVIEW: Headache following concussion and mild traumatic brain injury
      is very common in pediatrics. There is significant concern about appropriate
      management of acute and persistent headache following mild head injuries in
      children among affected youth, their families and care providers. RECENT
      FINDINGS: The current article will review definitions and diagnoses of
      posttraumatic headache (PTHA), recent research regarding risk factors for
      persistence of postconcussion symptoms and headaches, current recommendations for
      the evaluation of youth with PTHA, recent data regarding efficacy of treatment
      options for PTHA, and current recommendations for the treatment of acute and
      persistent PTHA. SUMMARY: PTHA is common following concussion in pediatrics. Some
      of the most consistent risk factors for persistent symptoms following concussion
      include female sex, adolescent age, prior concussion with prolonged recovery,
      prior headache history and high number of acute symptoms, particularly migrainous
      symptoms, following concussion. There are few prospective studies of the
      treatment of PTHA in pediatrics; however, a recent study found that short-term
      use of ibuprofen for those with acute PTHA following concussion may be associated
      with lower risk of symptoms and better function 1 week after injury. Currently
      complete rest or cocooning following concussion is not recommended as it may
      actually be associated with longer recovery time; a gradual return to cognitive
      and physical activity appears to be most effective strategy but more study is
      needed.

PMID- 30188412
TI  - Reply to "How Far can we Expand Donor Age Criteria for Pancreas Transplantation?"

PMID- 30188413
TI  - Pulse Pressure and Outcome in Kidney Transplantation: Results From the
      Collaborative Transplant Study.
AB  - BACKGROUND: Systolic (SBP) and diastolic blood pressure (DBP) are important
      predictors of graft and patient survival in renal transplantation. Pulse pressure
      (PP), the difference between systolic and diastolic pressure, has been associated
      with cardiovascular and renal morbidity in nontransplant epidemiological studies
      and clinical trials. METHODS: In this large retrospective analysis of
      prospectively collected data, transplant recipients from 1995 to 2015 were
      examined for patient and death-censored graft survival. RESULTS: In 43 006
      recipients a higher 1-year PP was significantly associated with inferior 10-year
      patient and death-censored graft survival. In patients aged >=60 SBP but not DBP
      was associated with 10-year survival, an effect that was pronounced in patients
      with a normal SBP of <140 mmHg and an increased PP of >=60 mmHg, highlighting the
      superior impact of PP on survival in elderly recipients. In recipients' >=60
      years, higher PP was associated with increased mortality due to circulatory
      system diseases but not to infection or cancer. The combination of PP >=60 and
      high SBP >=140 mmHg showed the strongest association with death-censored graft
      survival across all age groups. CONCLUSIONS: We found convincing evidence that PP
      1-year posttransplant is predictive of patient survival especially in elderly
      recipients with normal SBP. Combined analysis of SBP and PP showed that high PP
      confers additional predictive information for patient survival beyond that
      derived from analysis of SBP alone. With regard to prediction of death-censored
      graft survival, the combination of high SBP and high PP showed the best
      correlation across all age groups.

PMID- 30188414
TI  - Pulse Pressure: A Risk Factor for Renal Transplant Failure or a Useful
      Therapeutic Target?

PMID- 30188415
TI  - How Far Can We Expand Donor Age Criteria for Pancreas Transplantation?

PMID- 30188416
TI  - Prognostic significance of fluorine-18 fluorodeoxyglucose positron emission
      tomography/computed tomography-derived metabolic parameters in surgically
      resected clinical-N0 nonsmall cell lung cancer.
AB  - OBJECTIVE: Our aim was to assess the significance of metabolic positron emission
      tomography (PET) parameters for the prediction of occult mediastinal lymph node
      metastasis (OLM) and recurrence in patients with clinical-N0 nonsmall cell lung
      cancer (NSCLC) after surgical resection and lymph node dissection. MATERIALS AND
      METHODS: We evaluated 98 patients with NSCLC [52 adenocarcinoma (ADC), 46
      squamous cell carcinoma (SQCC)] who had undergone initial/preoperative fluorine
      18 fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG
      PET/CT). Eligibility criteria for participation were clinically staged as N0 and
      no FDG uptake in mediastinal lymph nodes on preoperative PET/CT.
      Clinicopathological characteristics and the diagnosis of recurrence were obtained
      by reviewing the hospital records. Metabolic parameters [maximum standardized
      uptake value, mean standardized uptake value, metabolic tumor volume (MTV), total
      lesion glycolysis] were determined on F-FDG PET/CT images. The association of
      metabolic parameters with OLM and recurrence was assessed. RESULTS: OLM was found
      in 26 (26.53%) patients. T-stage, central location, and lymphovascular invasion
      were associated with OLM (respectively, P=0.007, 0.011, <0.001). None of the
      metabolic parameters was associated with OLM. Metabolic parameters of the tumor
      were significantly higher in patients with recurrence when the cohort was
      evaluated as a whole (P=0.002, 0.005, 0.016, and 0.004, respectively). In
      particular, there was a significant association between recurrence and tumor
      size, grade, stage, MTV (P<0.001), and TLG (P<0.001) in ADC. This association was
      not found in SQCC. Multivariate analysis showed that MTV was an independent
      prognostic factor for recurrence and associated with disease-free survival.
      CONCLUSION: Metabolic parameters of the primary tumor on preoperative F-FDG
      PET/CT could not predict OLM in patients with clinical-N0 NSCLC. MTV was an
      independent risk factor for recurrence in ADC, but not in SQCC.

PMID- 30188417
TI  - Gastric outlet obstruction: an uncommon consequence of common salt binge.

PMID- 30188419
TI  - Retrograde type A aortic dissection complicating endovascular therapy of type B
      aortic dissection and descending thoracic aneurysm disease.
AB  - PURPOSE OF REVIEW: Retrograde type A aortic dissection (RTAD) is a fatal
      complication after endovascular therapy of type B aortic dissection and
      descending thoracic aneurysm disease. This review aims to elaborate this lethal
      complication, the potential risks of its incidence, and feasible approaches to
      lower the occurrence rate. RECENT FINDINGS: Many articles have shown lower
      incidence of RTAD in patients with thoracic aneurysm than those with aortic
      dissection. Also, acute aortic dissection seems to be more vulnerable when
      compared with chronic aortic dissection. Recent studies that focused on the risk
      of RTAD revealed that the mismatch of stent, the weakness of the aortic wall and
      intraoperative aortic injury played important roles in the development of RTAD.
      The mismatch of stent includes implanting the stent with the top bare spring, the
      location of landing zone, the oversizing of the stent on the proximal landing
      zone, and etc. Some centers presented some measures to lower the risks, such as
      increasing the oversizing of the stent, avoiding the aortic tortuosity, and
      locating in the healthy landing zone. SUMMARY: Ongoing research with improved
      technology and techniques continues to unravel new understanding and preventive
      measures of RTAD after endovascular treatment of aortic dissection and descending
      thoracic aneurysm disease. Cardiologists and vascular surgeons should be aware of
      current evidence and implement guidelines in relation to endovascular therapy of
      aortic diseases.

PMID- 30188420
TI  - Genetics of coronary artery disease: should they impact the choice of
      revascularization?
AB  - PURPOSE OF REVIEW: Patients with multivessel coronary artery disease (CAD) may
      undergo revascularization by either percutaneous coronary intervention (PCI) or
      coronary artery bypass graft surgery (CABG). This review will discuss the use of
      polygenic risk scores for risk-stratification of patients with multivessel CAD in
      order to guide the choice of revascularization. RECENT FINDINGS: A 57-single
      nucleotide polymorphism (SNP)-polygenic risk score can accurately risk-stratify
      patients with CAD and identify those who will receive greater benefit from statin
      therapy. The most recent genomic studies reveal 243 different SNPs are now
      significantly associated with CAD. Randomized clinical trials comparing PCI vs.
      CABG (FREEDOM, SYNTAX, NOBLE, EXCEL) have uncovered factors related to CAD
      severity (diabetes, SYNTAX score) are critical determinants of outcomes after
      revascularization. SUMMARY: There is a need to discover predictors of outcomes
      after PCI vs. CABG to improve clinical decision-making in multivessel CAD. High
      polygenic risk score is associated with increased CAD severity and better
      outcomes with statin therapy. Randomized clinical trials indicate CAD severity is
      associated with better outcomes after CABG compared with PCI. Accordingly,
      polygenic risk score could also be associated with better outcomes after CABG vs.
      PCI and used to optimize revascularization for patients with multivessel CAD.

PMID- 30188421
TI  - Changes in US Mass Shooting Deaths Associated With the 1994-2004 Federal Assault
      Weapon Ban: Analysis of Open-Source Data.
AB  - BACKGROUND: A federal assault weapons ban has been proposed as a way to reduce
      mass shootings in the U.S. (U.S). The Federal Assault Weapons Ban (A.W.B.) of
      1994 made the manufacture and civilian use of a defined set of automatic and semi
      automatic weapons and large capacity magazines illegal. The ban expired in 2004.
      The period from 1994 to 2004 serves as a single-arm pre-post observational study
      to assess the effectiveness of this policy intervention. METHODS: Mass shooting
      data for 1981 to 2017 were obtained from three well-documented, referenced, and
      open-source sets of data, based on media reports. We calculated the yearly rates
      of mass shooting fatalities as a proportion of total firearm homicide deaths and
      per U.S. POPULATION: We compared the 1994-2004 federal ban period to non-ban
      periods, using simple linear regression models for rates and a Poison model for
      counts with a year variable to control for trend. The relative effects of the ban
      period were estimated with odds ratios. RESULTS: Assault rifles accounted for 430
      or 85.8% of the total 501 mass-shooting fatalities reported (95% CI 82.8, 88.9)
      in 44 mass-shooting incidents. Mass shootings in the U.S. accounted for an
      increasing proportion of all firearm-related homicides (coefficient for year =
      0.7, p = 0.0003), with increment in year alone capturing over a third of the
      overall variance in the data (Adjusted R-squared = 0.3). In a linear regression
      model controlling for yearly trend, the federal ban period was associated with a
      statistically significant 9 fewer mass shooting related deaths per 10,000 firearm
      homicides (p = 0.03). Mass-shooting fatalities were 70% less likely to occur
      during the federal ban period (Relative Rate = 0.30, 95% CI 0.22,0.39).
      CONCLUSIONS: Mass-shooting related homicides in the U.S. were reduced during the
      years of the federal assault weapons ban of 1994 to 2004. STUDY TYPE:
      Observational LEVEL OF EVIDENCE: III/IV.

PMID- 30188422
TI  - Clearing the Cervical Spine in Patients with Distracting Injuries: An AAST Multi
      Institutional Trial.
AB  - BACKGROUND: Single institution studies have shown that clinical examination of
      the cervical spine (c-spine) is sensitive for clearance of the c-spine in blunt
      trauma patients with distracting injuries. Despite an unclear definition, most
      trauma centers still adhere to the notion that distracting injuries adversely
      affect the sensitivity of c-spine clinical examination. A prospective AAST multi
      institutional trial was performed to assess the sensitivity of clinical
      examination screening of the c-spine in awake and alert blunt trauma patients
      with distracting injuries. METHODS: During the 42-month study period, blunt
      trauma patients 18 years and older were prospectively evaluated with a standard c
      spine examination protocol at 8 Level 1 trauma centers. Clinical examination was
      performed regardless of the presence of distracting injuries. Patients without
      complaints of neck pain, tenderness or pain on range of motion were considered to
      have a negative c-spine clinical examination. All patients with positive or
      negative c-spine clinical examination underwent computed tomography (CT) scan of
      the entire c-spine. Clinical examination findings were documented prior to the CT
      scan. RESULTS: During the study period, 2929 patients were entered. At least one
      distracting injury was diagnosed in 70% of the patients. A c-spine injury was
      found on CT scan in 7.6% of the patients. There was no difference in the rate of
      missed injury when comparing patients with a distracting injury to those without
      a distracting injury (10.4% vs 12.6%, p=0.601). Only one injury missed by
      clinical examination underwent surgical intervention and none had a neurological
      complication. CONCLUSIONS: Negative clinical exam may be sufficient to clear the
      cervical spine in awake and alert blunt trauma patients, even in the presence of
      a distracting injury. These findings suggest a potential source for improvement
      in resource utilization. LEVEL OF EVIDENCE: Level 3, Diagnostic Test.

PMID- 30188423
TI  - ACS-COT Verification Level Affects Trauma Center Management of Pelvic Ring
      Injuries and Patient Mortality.
AB  - BACKGROUND: Pelvic ring fractures represent a complex injury that requires
      specific resources and clinical expertise for optimal trauma patient management.
      We examined the impact of treatment variability for this type of injury at Level
      1 and 2 trauma centers on patient outcomes. METHODS: Trauma quality collaborative
      data (2011-2017) were analyzed. This includes data from 29 ACS-COT verified Level
      1 and Level 2 trauma centers. Inclusion criteria were adult patients (>= 16
      years), ISS >= 5, blunt injury, and evidence of a partially stable or unstable
      pelvic ring fracture injury coding as classified using Abbreviated Injury Scale
      version 2005, with 2008 updates. Patients directly admitted, transferred out for
      definitive care, with penetrating trauma, or with no signs of life were excluded.
      Propensity score matching was used to create 1:1 matched cohorts of patients
      treated at Level 1 or 2 trauma centers. Trauma center verification level was the
      exposure variable used to compare management strategies, resource utilization,
      and in-hospital mortality in univariate analysis. RESULTS: We selected 1,220 well
      matched patients, from 1,768 total patients, using propensity score methods (610
      Level 1 and 610 Level 2 cohort). There were no significant baseline
      characteristic differences noted between the groups. Patients with pelvic ring
      fractures treated at Level 1 trauma centers had significantly decreased mortality
      (7.7 vs. 11.6%, p=0.02). Patients treated at Level 2 trauma centers were less
      likely to receive interventional angiography, undergo complicated definitive
      orthopedic operative treatment, and to be admitted to an ICU.
      ConclusionsAdmission with a partially-stable or unstable pelvic ring injury to a
      Level 1 trauma center is associated with decreased mortality. Level 2 trauma
      centers had significantly less utilization of advanced treatment modalities. This
      variation in clinical practice highlights potential processes to emphasize in the
      appropriate treatment of these critically ill patients. LEVEL OF EVIDENCE: Level
      II, Economic/Decision.

PMID- 30188424
TI  - Left ventricular myocardial dysfunction in young and middle-aged ischemic stroke
      patients: the Norwegian stroke in the young study.
AB  - BACKGROUND: Hypertension is highly prevalent in ischemic stroke patients, but
      less is known about its impact on subclinical left ventricular (LV) dysfunction
      in such patients. METHODS: Conventional and speckle tracking echocardiography was
      performed in 276 young (15-44 years) and middle-aged (45-60 years) ischemic
      stroke patients (mean age 50 +/- 9 years, 66% men). Hypertension was defined as a
      history of hypertension, use of antihypertensive medications, persistently
      elevated blood pressure (BP) during hospitalization or elevated clinic BP
      (>=140/90 mmHg) and ambulatory BP (>=130/80 mmHg) at follow-up visits. LV
      myocardial dysfunction was assessed by peak systolic global longitudinal (GLS)
      and circumferential strain (GCS). RESULTS: Hypertension was present in 68% of
      patients and associated with higher age, BMI and LV mass, male sex and the
      presence of diabetes (all P < 0.01). Compared with normotensive patients,
      hypertensive patients had significantly lower peak systolic GLS (-16 +/- 3 vs. 
      19 +/- 2%, P < 0.001) and GCS (-16 +/- 3 vs. -18 +/- 4%, P < 0.001) while
      ejection fraction did not differ between groups (P = 0.134). In univariable
      regression analyses, reduced peak systolic GLS and GCS were both associated with
      hypertension (beta = 0.43 and 0.29, respectively, both P < 0.001). The
      association with hypertension remained significant for GLS (beta = 0.25) after
      adjustment for LV mass, ejection fraction, male sex, obesity and diabetes
      (multiple R = 0.35, P < 0.001), whereas the association of hypertension with
      reduced peak systolic GCS was attenuated. CONCLUSION: In ischemic stroke
      survivors, hypertension was associated with reduced peak systolic GLS but not GCS
      independent of confounders.

PMID- 30188425
TI  - Case of Erythema Multiforme Drug Eruption Induced by Ledipasvir/Sofosbuvir.

PMID- 30188427
TI  - Leadership myths.

PMID- 30188426
TI  - Engagement and retention in float pools: Keeping the team above water.

PMID- 30188428
TI  - Population health of refugees in rural communities.

PMID- 30188429
TI  - Factors Influencing Various Aspects of Patients' Knowledge of Oral
      Anticoagulation: Erratum.

PMID- 30188430
TI  - HCMR's new impact factor: How it happened.

PMID- 30188432
TI  - Curiosity and Compassion.

PMID- 30188433
TI  - 20.5 JHPN Initial Text.

PMID- 30188434
TI  - Applying a Balm: Medicating the Patient to Treat the (Moral) Distress of
      Caregivers.
AB  - Moral distress occurs when a nurse knows the right action but is impeded from
      taking that right action because of institutional constraints. Caring for
      patients who are dying might evoke distress, including moral distress. The
      distress from a difficult clinical situation is likely to permeate other areas of
      practice. In this article, 2 cases are used as a means to distinguish moral
      distress from other distress arising from clinical situations. Opportunities to
      alleviate distress include increasing knowledge, improved communication, enhanced
      collaboration, and development of institutional supports.

PMID- 30188435
TI  - Applying a Balm: Medicating the Patient to Treat the (Moral) Distress of
      Caregivers.

PMID- 30188436
TI  - The Management of Nausea at the End of Life.
AB  - The evaluation and management of nausea in patients near the end of life can be
      more challenging than that of nausea in patients undergoing antineoplastic
      therapies. Unlike in the oncology setting in which nausea is primarily managed
      using antiemetic regimens that have been developed with the neuropharmacology and
      emetogenic potentials of chemotherapy agents in mind, many patients receiving end
      of-life care have nausea of multifactorial etiology. Patients also may be older
      with reduced physiologic ability to metabolize and clear drugs. Therefore,
      typical antiemetics in regimens initially selected for oncology patients may be
      ineffective. In this article, the prevalence, manifestation, and pathophysiology
      of nausea experienced by patients near and at the end of life will be reviewed,
      with a focus on pharmacological and nonpharmacological interventions that have
      been found to effectively manage this symptom in this patient population.

PMID- 30188437
TI  - The Management of Nausea at the End of Life.

PMID- 30188438
TI  - Enhancing Cancer Pain Assessment and Management in Hospice.
AB  - Pain is one of the most common symptoms in individuals with cancer and is
      directly associated with significantly reduced quality of life. The purpose of
      this project was to enhance assessment and management of cancer-related pain for
      patients in the hospice setting. Nurse attitudes and knowledge about pain were
      evaluated using the Nurses' Knowledge and Attitudes Survey Regarding Pain before
      and 6 weeks after an educational program. Nurses completed a pain assessment at
      each home visit and followed an algorithm based on the National Comprehensive
      Cancer Network Clinical Practice Guidelines to manage pain. Baseline data were
      collected on the last 30 patients admitted into hospice with cancer as the
      primary diagnosis before project implementation. Following the practice change,
      chart audits of the patients' reported pain and adherence to recommended
      management were manually extracted from 26 patient records. Results revealed
      statistically significant differences in acquired knowledge (t = 3.95, P < .05)
      and attainment of patient-identified pain goals (t = 23.904, P < .05). Patient
      reported pain levels decreased by 21%, and comprehensive pain assessment
      completion rates increased by 10% during the project. Current knowledge of
      evidence-based pain interventions and a management algorithm improved pain
      control in patients with cancer.

PMID- 30188439
TI  - Educating Nurses About End-of-Life Care for Patients With Implanted Cardioverter
      Defibrillators.
AB  - Many people with implanted cardioverter defibrillators (ICDs) are living at home
      and receiving nursing services through home health care agencies. Near the end of
      life, it is not unusual for patients to request comfort measures and care that
      promotes quality rather than quantity of life. The purpose of this pilot study
      was twofold: (1) to educate home health care nurses on care of patients with ICDs
      nearing the end of life and (2) to measure changes in nurse knowledge pre to post
      educational session. None of the registered nurses in this study reported ever
      caring for a patient who had died with an ICD in place. Subsequently, their
      knowledge in end-of-life care surrounding this patient population significantly
      improved after the educational session (P < .006). Knowing how to care for such
      patients as they are dying is imperative for nurses, especially because many ICD
      recipients have insufficient knowledge themselves and can benefit from education
      provided by nurses.

PMID- 30188440
TI  - Exploration of Families' Experiences Caring for Loved Ones With Advanced Ovarian
      Cancer.
AB  - Ovarian cancer is challenging, both physically and psychologically, because of
      the advanced nature of the disease at diagnosis, adverse effects of the disease
      and treatment, and impact on roles and responsibilities. The family plays an
      integral role in promoting and maintaining the health of family caregivers, as
      well as providing physical and emotional support. The purpose of this study was
      to explore the experience of family caregivers caring for their loved ones with
      advanced ovarian cancer. Thirteen family caregivers were interviewed. The
      analysis of the data revealed 4 significant challenges that characterized the
      caregiving experience over time: confronting the initial diagnosis, dealing with
      fluctuations in physical status, confronting a turning point, and facing decline
      and death. Woven throughout these challenges, family caregivers routinely
      described difficulties in accessing information and navigating the health care
      system, which caused them added concern and frustration.

PMID- 30188441
TI  - Self-efficacy and Stress Among Informal Caregivers of Individuals at End of Life.
AB  - Researchers have established associations between the stressors of providing
      informal care and caregiver health risks. Despite the negative consequences,
      researchers have identified the existence of protective factors that have the
      potential to buffer or prevent stress. The purpose of this study was to determine
      the relationship between self-efficacy and stress in adult informal caregivers
      providing end-of-life care. This cross-sectional, associational study analyzed
      data from questionnaires completed by adult informal caregivers providing end-of
      life care for an adult in North Texas. Questionnaires provided measures of self
      efficacy, stress, and caregiver perceived health. Findings indicated caregiver
      self-efficacy globally had a significant correlation with stress, whereas
      caregivers' confidence in caring for themselves had a significant negative
      relationship with perceived stress. Specifically, study findings indicate
      caregivers with greater confidence in managing demands of caregiving have lower
      levels of stress, and caregivers with greater confidence in caring for
      themselves, specifically, have lower levels of perceived stress. Study findings
      highlight the importance of caregivers' self-care needs. Health care
      practitioners should recognize and intervene to support caregivers' self-care
      needs in order to prevent additional, needless health problems in this
      population.

PMID- 30188442
TI  - What Matters to Persons With Dementia at the End of Life: Perspectives of Proxy
      Decision Makers.
AB  - For substituted decision makers for the growing number of persons with dementia
      (PWDs), understanding the PWD's values is a prerequisite for making end-of-life
      (EOL) decisions congruent with the PWD's wishes. The current qualitative study
      explored PWD health care proxies' perspectives on values that are important to
      PWDs at end of life and challenges in making EOL decisions that reflect PWDs'
      values. Semistructured interviews were conducted with 20 PWD proxies, and data
      were analyzed using the content analysis, an inductive approach to identify
      themes. Three main themes emerged: (1) what matters to PWDs at end of life, (2)
      uncertainty about the PWD's current wishes and EOL trajectory poses challenges,
      and (3) the role of health care professionals' empathic and clear communication.
      Together, these findings suggest proxies' efforts to understand and respect PWDs'
      wishes at end of life and communication strategies that health care providers can
      use to help PWD proxies cope with uncertainty and challenges in EOL decision
      making.

PMID- 30188443
TI  - Pilot of a Pediatric Palliative Care Early Intervention Instrument.
AB  - Current research demonstrates that pediatric symptom management care is often
      initiated in the late stages of disease once clinicians are no longer able to
      meaningfully impact symptom burden. Given that physicians or nurse practitioners
      are responsible for initiating palliative care referrals, it is incumbent upon
      registered nurses to advocate when improved symptom management care is needed.
      The pediatric palliative care screening instrument pilot provides a centralized
      instrument to document and quantify a patient's symptom profile, giving
      registered nurses the opportunity to objectively communicate and track a
      patient's need for improved symptom management care within the areas of pain,
      secretions, dyspnea, intractable seizures, nausea, vomiting, constipation,
      diarrhea, anorexia, cachexia, sleep disturbance, lethargy, anxiety, depression,
      and/or agitation. The 4-week quality improvement project at an academic teaching
      hospital formally incorporated the bedside registered nurses' symptom assessment
      into a centralized document. Fifty-three patients were identified as having an
      uncontrolled symptom burden in at least one of the symptom domains, indicating
      that excessive and untreated symptom burden was present on the acute care floor.
      The pediatric palliative care screening instrument could act as a conduit between
      bedside registered nurses and the palliative care team, serving to reduce the
      time between onset of excessive symptom burden and initiation of symptom
      management services.

PMID- 30188444
TI  - Losing Health Symbols Because of Nutrition-Related Problems in Advanced Cancer:
      An Interpretative Phenomenological Analysis.
AB  - Cancer and nutrition-related problems are extremely distressing events and
      disturb functioning and daily life. It is recognized that the effects of
      stressors challenging well-being are mediated by the meaning attached to these
      stressors. As nutrition-related problems are often being experienced within
      couples, it is also important to gain understanding of a partner's interpretation
      of complaints and whether it coincides with that of the patient.To explore the
      meaning attached to nutrition-related problems, a qualitative approach was
      followed. Seven couples, each composed of a patient with cancer and his/her
      cohabiting life partner, participated. Data were collected through in-depth
      interviews and analyzed by an interpretative phenomenological approach.Nutrition
      related problems among patients with advanced cancer are mostly perceived as
      destroying health and leading to loss of physical, psychological, and social
      health symbols. Because the meaning patients and their partners attach to
      nutrition-related problems is individual and dynamic, it is necessary to devote
      special attention to the issues on different occasions.The study findings can
      assist nurses and other professional caregivers in providing psychological
      support for couples confronted with nutrition-related problems in advanced
      cancer. It is important to take into account the meaning patients and partners
      attach to these nutrition-related problems.

PMID- 30188445
TI  - Lessons From an Immersion Experience in Southern India.
AB  - Approximately 2.4 million people in India are living with cancer, and more than 1
      million new cancer diagnoses are made annually, often in advanced stages of
      disease. An estimated 80% of patients with advanced cancer will develop
      significant pain resulting in the need to increase access to appropriate
      palliative care services across the country, including a priority on pain and
      symptom management. This article describes the history and status of palliative
      care across India, with an emphasis on the efforts made in the southern state of
      Kerala to engage community volunteers in the care of patients with chronic
      serious illness. Lessons learned from a palliative care nurse fellow's 2-week
      immersion in southern India are shared.

PMID- 30188446
TI  - HPNA Position Statement Advance Care Planning.

PMID- 30188447
TI  - World Gastroenterology Organisation (WGO) News and Events.

PMID- 30188450
TI  - INS 2018 ePoster Presentations.

PMID- 30188449
TI  - Authors, Beware of Predatory Publishing.

PMID- 30188451
TI  - Effects of Thermomechanical Stimulation During Intravenous Catheter Insertion in
      Adults: A Prospective Randomized Study.
AB  - This was an open-label, randomized clinical trial comparing the effects of
      thermomechanical stimulation (Buzzy) versus no intervention in 105 adults
      undergoing intravenous (IV) catheter insertion before elective orthopedic
      surgical procedures. A visual analog scale was used to measure pain; satisfaction
      questionnaires were administered after IV catheter insertion. There was no
      significant difference in the mean pain score between the experimental (n = 49)
      and control (n = 56) groups (2.52 vs 2.43, P = .86). Subjects who reported higher
      preprocedure anxiety benefited most from the test intervention. It was determined
      that the application of cold and vibration is not universally effective for pain
      prevention during IV catheter insertion or for improvement in patient
      satisfaction in preoperative care.

PMID- 30188452
TI  - Evaluation of a Magnetic Tracking and Electrocardiogram-based Tip Confirmation
      System for Peripherally Inserted Central Catheters in Pediatric Patients.
AB  - The purpose of this study was to investigate whether a magnetic tracking and
      electrocardiogram-based tip confirmation system (TCS) (Sherlock 3CG Tip
      Confirmation System; Bard, Covington, GA) permits safe and correct placement of a
      peripherally inserted central catheter (PICC) in the pediatric population. A
      total of 144 PICCs were placed using the TCS. After excluding participants for
      various reasons, 112/121 (92.56%) of PICCs were appropriately placed using the
      TCS. The TCS confirmed tip location an average of 7 to 18 minutes faster than
      radiographic imaging. There were no complications associated with the insertion
      of the PICCs using the TCS.

PMID- 30188453
TI  - Perceptions of Infusion Pump Alarms: Insights Gained From Critical Care Nurses.
AB  - Between 1983 and 2011, equipment-related alarms in critical care have increased
      from 6 to 40 different alarm types. As nurses become overwhelmed, distracted, or
      desensitized by alarm noise, they may miss critical alarms that could result in
      patient harm. The findings of an infusion pump alarm survey indicated that nurses
      overwhelmingly agree that infusion pump nuisance alarms occur frequently and
      disrupt patient care. But nurses' perceptions of pump alarms are different from
      those previously reported for clinical alarms in general. It may not be
      appropriate to broadly apply general alarm management recommendations to infusion
      pump alarms at this time.

PMID- 30188454
TI  - Best Practices in the Management of Central Vascular Access Devices: An
      Observational Study in Areas With a High Prevalence of Trained Nurses.
AB  - Since 2009, the Department of Continuing Education at the Orthopedic and Trauma
      Center Hospital in Turin, Italy, has provided a training course for nurses in the
      management of central vascular access devices (CVADs). The course focuses on
      dressing and flushing procedures, as well as compliance with other CVAD
      guidelines. An observational study was conducted among nurses to determine the
      level of best practices in areas with a high prevalence of nurses trained in the
      management of CVADs. A correlation was observed between best practices and having
      attended the course, but other variables also influenced best practices.

PMID- 30188455
TI  - Mesenchymal stem cell exosomes as a cell-free therapy for nerve injury-induced
      pain in rats.
AB  - Nerve injury-induced neuropathic pain is difficult to treat. In this study, we
      used exosomes derived from human umbilical cord mesenchymal stem cell (UCMSC) as
      a cell-free therapy for nerve injury-induced pain in rats. Isolated UCMSC
      exosomes range in size from 30 to 160 nm and contain CD63, HSP60, and CD81
      exosome markers. After L5/6 spinal nerve ligation surgery, single intrathecal
      injection of exosomes reversed nerve ligation-induced mechanical and thermal
      hypersensitivities of right hindpaw of rats at initial and well-developed pain
      stages. Moreover, continuous intrathecal infusion of exosomes achieved excellent
      preventive and reversal effects for nerve ligation-induced pain. In
      immunofluorescent study, lots of Exo-green-labelled exosomes could be found
      majorly in the ipsilateral L5 spinal dorsal horn, dorsal root ganglion, and
      peripheral axons, suggesting the homing ability of UCMSC exosomes. They also
      appeared in the central terminals or cell bodies of IB4, CGRP, and NF200 sensory
      neurons. In addition, exosome treatment suppressed nerve ligation-induced
      upregulation of c-Fos, CNPase, GFAP, and Iba1. All these data suggest that the
      analgesic effects of exosomes may involve their actions on neuron and glial
      cells. Exosomes also inhibited the level of TNF-alpha and IL-1beta, while
      enhanced the level of IL-10, brain-derived neurotrophic factor, and glial cell
      line-derived neurotrophic factor in the ipsilateral L5/6 dorsal root ganglion of
      nerve-ligated rats, indicating anti-inflammatory and proneurotrophic abilities.
      Protein analysis revealed the content of vascular endothelial growth factor C,
      angiopoietin-2, and fibroblast growth factor-2 in the exosomes. In summary,
      intrathecal infusion of exosomes from UCMSCs may be considered as a novel
      therapeutic approach for nerve injury-induced pain.

PMID- 30188456
TI  - Neuropathic pain and pain interference are linked to alpha-band slowing and
      reduced beta-band magnetoencephalography activity within the dynamic pain
      connectome in patients with multiple sclerosis.
AB  - Chronic pain is a common occurrence in multiple sclerosis (MS) that severely
      affects quality of life, but the underlying brain mechanisms related to these
      symptoms are unknown. Previous electroencephalography studies have demonstrated a
      role of alpha-band and beta-band power in pain processing. However, how and where
      these brain signals change in MS-related chronic pain is unknown. Here, we used
      resting state magnetoencephalography to examine regional spectral power in the
      dynamic pain connectome-including areas of the ascending nociceptive pathway,
      default mode network (DMN), and the salience network (SN)-in patients with
      chronic MS pain and in healthy controls. Each patient was assessed for pain,
      neuropathic pain (NP), and pain interference with activities of daily living. We
      found that patients with MS exhibited an increase of alpha-band power and a
      decrease of beta-band power, most prominently in the thalamus and the posterior
      insula of the ascending nociceptive pathway and in the right temporoparietal
      junction of the SN. In addition, patients with mixed-NP exhibited slowing of
      alpha peak power within the thalamus and the posterior insula, and in the
      posterior cingulate cortex of the DMN. Finally, pain interference scores in
      patients with mixed-NP were strongly correlated with alpha and beta peak power in
      the thalamus and posterior insula. These novel findings reveal brain mechanisms
      of MS-related pain in the ascending nociceptive pathway, SN, and DMN, and that
      these spectral abnormalities reflect the impact of pain on quality of life
      measures.

PMID- 30188457
TI  - Why Do We Need a New Clinical Practice Guideline for Moderate to Severe Traumatic
      Brain Injury?
AB  - OBJECTIVE: Clinical practice guidelines (CPGs) aim to improve quality and
      consistency of healthcare services. A Canadian group of researchers, clinicians,
      and policy makers developed/adapted a CPG for rehabilitation post-moderate to
      severe traumatic brain injury (MSTBI) to respond to end users' needs in acute
      care and rehabilitation settings. METHODS: The rigorous CPG development process
      began assessing needs and expectations of end users, then appraised existing
      CPGs, and, during a consensus conference, produced fundamental and priority
      recommendations. We also surveyed end users' perceptions of implementation gaps
      to determine future implementation strategies to optimize adherence to the CPG.
      RESULTS: The unique bilingual (French and English) CPG consists of 266
      recommendations (of which 126 are new recommendations), addressing top priorities
      for MSTBI, rationale, process indicators, and implementations tools (eg,
      algorithms and benchmarks). CONCLUSION: The novel approach of consulting and
      working with end users to develop a CPG for MSTBI should influence knowledge
      uptake for clinicians wanting to provide evidence-based care.

PMID- 30188458
TI  - Assessment of Users' Needs and Expectations Toward Clinical Practice Guidelines
      to Support the Rehabilitation of Adults With Moderate to Severe Traumatic Brain
      Injury.
AB  - OBJECTIVE: Stakeholder engagement in clinical practice guideline (CPG) creation
      is thought to increase relevance of CPGs and facilitate their implementation. The
      objectives were to survey stakeholders involved in the care of adults with
      traumatic brain injury (TBI) regarding general perceptions of CPGs, key elements
      to be included, and needs and expectations about format and implementation
      strategy. SETTINGS: Hospitals and inpatient and outpatient rehabilitation
      facilities providing services to persons with TBI. PARTICIPANTS: Stakeholders
      identified as primary end users of the CPG: clinicians, hospital leaders, health
      system managers, and funders in Quebec and Ontario (Canada). DESIGN: Cross
      sectional online survey conducted between May and September 2014. RESULTS: In
      total, 332 individuals expressed their needs and expectations. Despite positive
      perceptions of CPGs, only a small proportion of respondents used them. Intensity
      and frequency of interventions, behaviors disorders and cognitive function
      impairment, and social participation and community life were important subjects
      to cover in the CPG. Finally, respondents asked for specific recommendations
      including a ranking of recommendations based on level of underlying evidence.
      CONCLUSION: Respondents have important expectations toward a CPG. We anticipate
      that early and meaningful engagement of end users could facilitate CPG
      implementation.

PMID- 30188459
TI  - Unique Features of the INESSS-ONF Rehabilitation Guidelines for Moderate to
      Severe Traumatic Brain Injury: Responding to Users' Needs.
AB  - OBJECTIVE: Traumatic brain injury (TBI) clinical practice guidelines are a
      potential solution to rapidly expanding literature. The project objective was to
      convene experts to develop a unique set of TBI rehabilitation recommendations
      incorporating users' priorities for format and implementation tools including
      indicators of adherence. METHODS: The Guidelines Adaptation & Development Cycle
      informed recommendation development. Published TBI recommendations were
      identified and tabulated. Experts convened to adapt or, where appropriate,
      develop new evidence-based recommendations. These draft recommendations were
      validated by systematically reviewing relevant literature. Surveys of experts and
      target users were triangulated with strength of evidence to identify priority
      topics. RESULTS: The final recommendation set included a rationale,
      implementation tools (algorithms/adherence indicators), key process indicators,
      and evidence summaries, and were divided in 2 sections: Section I: Components of
      the Optimal TBI Rehabilitation System (71 recommendations) and Section II:
      Assessment and Rehabilitation of Brain Injury Sequelae (195 recommendations). The
      recommendations address top priorities for the TBI rehabilitation system: (1)
      intensity/frequency of interventions; (2) rehabilitation models; (3) duration of
      interventions; and (4) continuity-of-care mechanisms. Key sequelae addressed (1)
      behavioral disorders; (2) cognitive dysfunction; (3) fatigue and sleep
      disturbances; and (4) mental health. CONCLUSION: This TBI rehabilitation
      guideline used a robust development process to address users' priorities.

PMID- 30188461
TI  - Options for Evaluating and Tracking Pediatric Concussion.

PMID- 30188460
TI  - A Survey of Perceived Implementation Gaps for a Clinical Practice Guideline for
      the Rehabilitation of Adults With Moderate to Severe Traumatic Brain Injury.
AB  - OBJECTIVE: Appraising current practice is an important prerequisite for
      implementation of clinical practice guidelines (CPGs). The study objective was to
      determine the perceived level of implementation, priority, and feasibility of a
      subset of key CPG recommendations for the rehabilitation of individuals with
      moderate to severe traumatic brain injury (MSTBI). METHODS: Fifty-one teams at
      acute care and rehabilitation facilities were invited to complete an electronic
      survey addressing the perceived level of implementation, priority, and
      feasibility of 109 fundamental and priority recommendations from the CPG-MSTBI.
      RESULTS: Forty-four clinical teams responded across 2 Canadian provinces. Most of
      the recommendations were deemed as "fully" or "mostly" implemented, while
      relative gaps in implementation were perceived in recommendations regarding
      coordination with mental health and addiction providers (>75% of respondents
      indicated low levels of implementation), "Caregivers and Families" (26%), and
      "Psychosocial and Adaptation Issues" (25%). Priority levels and perceived
      feasibility were generally high (>60% and >86%, respectively) for recommendations
      with low levels of implementation. Priority recommendations for implementation
      were identified for both acute care and rehabilitation settings in Quebec and
      Ontario. CONCLUSIONS: Assessment of clinician perception provides a helpful
      perspective for implementation. Exploring perceived implementation gaps based on
      users' needs and expectation should be a part of an implementation process.

PMID- 30188463
TI  - A Phenotype of Primary Open-angle Glaucoma With Systemic Vasospasm.
AB  - PURPOSE: Primary open-angle glaucoma (POAG) patients constitute a heterogenous
      group. Identification of phenotypic subtypes among these patients may provide a
      deeper understanding of the disease and aid associations with genotypes. We
      describe a phenotype of POAG patients associated with a constellation of systemic
      disorders; patients with this phenotype seem to be vulnerable to optic nerve
      damage at low intraocular pressures. MATERIALS AND METHODS: In this retrospective
      study, we evaluated the medical records of active Jules Stein Eye Institute
      glaucoma patients from January 1996 to 2017 and included subjects with POAG,
      acquired pits of the optic nerve (APON), and at least one of the following:
      systolic blood pressure persistently <=100 mm Hg, history of migraine headaches
      or migraine variant, and the Raynaud syndrome. RESULTS: Of 87 patients (125 eyes)
      with APON, 37 patients (55 eyes) met the study criteria. In total, 34 patients
      were female (92%). The median age at the time of diagnosis was 55 years. Nineteen
      patients (73%) had low systolic blood pressures, same number had Raynaud
      syndrome, and 25 (68%) had a history of migraine. CONCLUSIONS: We describe a POAG
      subtype with APON and systemic vascular instability, predominantly female in
      their sixth decade of life who demonstrate progressive glaucomatous visual field
      damage at low intraocular pressure. We suggest that this clinical picture
      represents an important phenotype of POAG, and that identification and further
      study of it will help guide diagnosis and development of individualized
      treatments.

PMID- 30188464
TI  - Self-perceived Impact of Glaucomatous Visual Field Loss and Visual Disabilities
      on Driving Difficulty and Cessation.
AB  - PURPOSE: To investigate if glaucoma severity and the presence of self-reported
      glare and difficulty with dark adaptation are associated with driving difficulty
      or cessation. PATIENTS AND METHODS: Individuals with glaucoma, age 50+ and visual
      acuity in the better eye >=20/50 were included. Glaucoma severity was defined by
      the visual field mean deviation (MD) in the better eye and was classified into 2
      groups: mild (MD>-6 dB) and moderate/severe (MD<=-6 dB). Patient responses to the
      glare and dark adaptation subscales in Glaucoma Quality of Life-15 questionnaire
      were used to measure relevant visual disability. Associations were assessed
      utilizing prevalence ratios (PR). RESULTS: A total of 99 participants (57%
      female) were included with 19% (19/99) reporting driving cessation. Patients with
      moderate/severe glaucoma when compared with mild glaucoma reported a
      significantly higher percentage of driving cessation (33% vs. 8%; P=0.002),
      presence of glare (27% vs. 6%; P=0.012), and difficulty with dark adaptation (31%
      vs. 10%; P=0.011).Individuals with self-perceived difficulty with dark adaptation
      were about 4 times more likely than those without to have difficulty driving at
      night (adjusted PR=3.94; P<0.0001) or in poor driving conditions (adjusted
      PR=4.09; P=0.0002). Self-reported glare was associated with an increased risk of
      driving difficulty in poor driving conditions (PR=4.17; P=0.05). CONCLUSIONS:
      Patients with moderate/severe glaucomatous visual field loss reported
      significantly higher percentage of driving cessation, presence of glare and
      difficulty with dark adaptation. Difficulty with dark adaptation was
      significantly associated with difficulty driving at night or in poor driving
      conditions. Further studies are needed to confirm these findings.

PMID- 30188465
TI  - Prediction of Surgical Outcome After Trabeculectomy for Neovascular Glaucoma With
      Anterior-segment Optical Coherence Tomography.
AB  - PURPOSE: To determine the potential of anterior-segment optical coherence
      tomography (AS-OCT) to predict posttrabeculectomy outcomes in neovascular
      glaucoma (NVG). PATIENTS AND METHODS: We recruited 45 eyes of 40 NVG patients who
      underwent trabeculectomy. The patients were divided into success and failure
      groups based on the posttrabeculectomy outcome after 12 months. AS-OCT findings
      were compared in the success and failure groups at 1 and 2 weeks and 1, 3, 6, and
      12 months. We also analyzed early posttrabeculectomy bleb parameters with
      multiple logistic regression, stepwise multiple regression, and the receiver
      operating characteristic curve to evaluate the power of these parameters to
      predict long-term outcomes. RESULTS: Intraocular pressure at 6 and 12 months was
      lower in the success group than the failure group (P<0.0016=0.0048). Reflectivity
      of the bleb wall was higher in the failure group than the success group
      throughout the study (all: P<0.0016). Age and reflectivity of the bleb wall at 1
      week were risk factors for failure with odds ratios for failure of 0.91 and 1.67.
      The area under the receiver operating characteristic curve for reflectivity of
      the bleb wall at 1 week was 0.943 with the cutoff set at 128.9 (sensitivity:
      85.7%; specificity: 100.0%). Stepwise multiple regression analysis showed that
      reflectivity of the bleb wall at 1 week independently indicated the bleb survival
      period (beta=-0.84; P<0.001). CONCLUSIONS: AS-OCT-measured reflectivity of the
      bleb wall, measured at 1 week of trabeculectomy for NVG, might be able to predict
      of the final status of the bleb.

PMID- 30188466
TI  - EX-PRESS Ab Externo Revision With a 41-G Needle.
AB  - The EX-PRESS Glaucoma Filtration Device is a stainless steel, nonvalved
      filtration device that channels aqueous humor through a secure lumen to a half
      thickness scleral flap, creating a subconjunctival filtration bleb. Elevated
      postoperative intraocular pressure may indicate occlusion of the device lumen or
      episcleral fibrosis, and it is essential to reestablish the flow in a timely
      manner to prevent bleb formation failure. We report the successful use of an
      extendible 41-G subretinal injection needle to rapidly restore device patency
      when the conventional bleb revision was not effective.

PMID- 30188467
TI  - Contralateral Botulinum Toxin Improved Functional Recovery after Tibial Nerve
      Repair in Rats.
AB  - BACKGROUND: There is clinical and experimental evidence that botulinum toxin
      applied to the healthy side of patients with facial paralysis positively affects
      functional recovery of the paralyzed side. The authors created an experimental
      model to study the effects of botulinum toxin injection in the gastrocnemius
      muscle contralateral to the side of tibial nerve lesion/repair in rats. METHODS:
      Fifty rats were allocated into five groups: group I, control; group II, tibial
      nerve section; group III, tibial nerve section and immediate neurorrhaphy; group
      IV, tibial nerve section, immediate neurorrhaphy, and botulinum toxin injected
      into the contralateral gastrocnemius muscle; and group V, botulinum toxin
      injected into the gastrocnemius muscle and no surgery. Assessment tools included
      a walking track, electromyography, gastrocnemius muscle weight measurement, and
      histologic analysis of the nerve. RESULTS: Paralysis in group V was transient,
      with function returning to normal at 8 weeks. At 12 weeks, group V had lower
      latency levels. At week 12, group IV showed higher functional outcomes and
      amplitude levels than group III, and lower muscle atrophy on the side injected
      with botulinum toxin compared with group V. CONCLUSION: Transient paralysis of
      the contralateral gastrocnemius muscle by botulinum toxin type A improved
      functional recovery in rats that underwent section and repair of the tibial
      nerve.

PMID- 30188468
TI  - Clockwise and Counterclockwise Le Fort I Movements Influence Nasolabial
      Morphology Differently.
AB  - BACKGROUND: Le Fort I maxillary advancements affect nasal proportions. However,
      there are no data on the three-dimensional nasal changes that occur with
      differential lateral plane adjustment (clockwise and counterclockwise movements)
      during Le Fort I maxillary advancements. This study analyzes and compares
      nasolabial soft-tissue changes after Le Fort I clockwise and counterclockwise
      repositioning. METHODS: Single-piece Le Fort I advancements were included. A
      retrospective study of patients split into clockwise and counterclockwise groups
      was performed. Preoperative and postoperative three-dimensional photographs
      (VECTRA 3D) were analyzed. Nasolabial anthropometric measurements were recorded
      using Mirror software. Statistical analysis involved paired t test to compare
      preoperative and postoperative measurements. RESULTS: Twenty-four patients were
      evaluated (12 per group), with 22 distinct nasolabial relationships measured.
      Counterclockwise movement showed a statistically significant increase in alar
      width (3.6 mm; p < 0.001), alar base width (1.6 mm; p = 0.009), oral width (3.2
      mm; p = 0.02), and lip projection (3.4 mm; p = 0.04). Clockwise movement showed
      no statistically significant changes, with the largest position changes noted in
      alar width (2.7 mm; p = 0.07) and alar base width (1.7 mm; p = 0.09).
      CONCLUSIONS: Clockwise and counterclockwise Le Fort I advancements have a
      different effect on postoperative nasolabial morphology. Counterclockwise
      movements exhibit significant changes, widening the alar base and width and the
      oral and philtral widths. The impact on the nostril morphology and columella was
      similar between the groups. The differential impact on nasolabial appearance is
      important to recognize for treatment planning and patient counseling. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

PMID- 30188469
TI  - Neural Perforasomes of the Upper Extremity.
AB  - BACKGROUND: In the setting of the rapid advancement of integumentary vascular
      knowledge, the authors hypothesized that the extrinsic blood supply to the major
      peripheral nerves of the upper extremity could be categorized into discrete
      neural "perforasomes." METHODS: Total limb perfusion of the arterial system was
      performed with gelatin-red lead oxide in cadaveric upper limbs. The perforating
      vessels to the radial, median, and ulnar nerves were identified, confirmed with
      fluoroscopy, and dissected. Distances to major anatomical landmarks of the upper
      extremity were measured. Additional cadaveric limbs' nerves were dissected and
      source arteries were selectively cannulated and injected to assess specific
      contribution to extrinsic nerve perfusion. The perfusion of each nerve was then
      calculated among all specimens. RESULTS: The radial, median, and ulnar nerve
      perforators were mapped. The corresponding neural perforasomes were mapped. The
      distal portions of the superficial radial nerve and the posterior interosseous
      nerve demonstrated a lack of staining. Similarly, at the carpal tunnel and at the
      proximal 25 percent of the median nerve (corresponding to the pronator teres),
      the nerve lacked vascular staining. At the Guyon canal and the flexor carpi
      ulnaris, the ulnar nerve demonstrated a lack of vascular staining. CONCLUSIONS:
      Peripheral nerves can be divided into neural perforasomes with limited overlap.
      The extrinsic perfusion of peripheral nerves is highly segmental. Absent stains
      within the nerves correspond to common sites of compression: carpal tunnel and
      pronator teres for the median nerve, supinator for the posterior interosseous
      nerve, and the Guyon canal and the flexor carpi ulnaris for the ulnar nerve.

PMID- 30188470
TI  - Effects of Extracorporeal Shock Wave Therapy on Distraction Osteogenesis in Rat
      Mandible.
AB  - BACKGROUND: Distraction osteogenesis has widespread clinical use in the treatment
      of congenital and acquired craniofacial deformities. Nonetheless, during the
      prolonged consolidation period, the newly regenerated bone carries the risk of
      complications. A known method for enhancing bone healing is extracorporeal shock
      wave therapy, which has been shown to induce neovascularization and promote
      tissue regeneration. The authors investigated whether extracorporeal shock wave
      therapy can accelerate bony consolidation and regeneration in distraction
      osteogenesis of the rat mandible and at which stage of distraction osteogenesis
      it should be applied. METHODS: Twenty-four male Sprague-Dawley rats were
      subjected to distraction osteogenesis of the right mandible (latency period, 3
      days; distraction period, 10 days; 0.5 mm/day). Experimental groups consisted of
      the following: group I (control), no extracorporeal shock wave therapy; group II,
      extracorporeal shock wave therapy (0.18 mJ/mm) at the latency period; and group
      III, extracorporeal shock wave therapy (0.18 mJ/mm) at the consolidation period.
      Explants were removed for evaluation after 4 weeks of consolidation. RESULTS:
      Histologic evaluation showed well-developed cortical cortex and a higher degree
      of bone formation and mature bone in group III; micro-computed tomography showed
      significantly increased bone mineral density, bone volume fraction, and
      trabecular thickness; immunohistochemistry demonstrated significantly increased
      expression of bone morphogenetic protein-2, vascular endothelial growth factor,
      and proliferating cell nuclear antigen. CONCLUSION: Extracorporeal shock wave
      therapy application at the consolidation period during distraction osteogenesis
      in the rat mandible enhances bone formation and osteogenic and angiogenic growth
      factors, improves bone mechanical properties, and accelerates bone
      mineralization.

PMID- 30188471
TI  - Noninvasive Flap Preconditioning by Foam-Mediated External Suction Improves the
      Survival of Fasciocutaneous Axial-Pattern Flaps in a Type 2 Diabetic Murine
      Model.
AB  - BACKGROUND: Advances in reconstructive surgery are leading to an increased number
      of flaps at risk for ischemic necrosis, because of either intrinsic (e.g., larger
      flap size) or extrinsic (e.g., diabetes) factors. Methods to preoperatively
      improve flap vascularity and limit postoperative ischemia are lacking.
      Noninvasive suction, using either a macrodeformational silicone cup interface
      (external volume expansion) or a microdeformational polyurethane foam interface
      (foam-mediated external volume expansion), has been shown to induce angiogenesis
      in tissues. The authors investigated whether the preoperative use of external
      volume expansion/foam-mediated external volume expansion improves flap survival
      in an obesity-induced diabetic animal model. METHODS: Db/Db mice underwent either
      mechanical stimulation with suction for 5 days using either external volume
      expansion or foam-mediated external volume expansion, or received no stimulation
      (n = 8 per group). Five days after the last stimulation, a critical-size, axial
      pattern, fasciocutaneous flap was raised in all animals. Postoperatively, flap
      survival was monitored with digital imaging for 10 days. After this period, flaps
      were harvested to assess tissue survival, angiogenesis, and inflammation, using
      histology and polymerase chain reaction. RESULTS: Foam-mediated external volume
      expansion preconditioning significantly increased the viable flap area (28
      percent), viable flap volume (27 percent), and flap capillary density (36
      percent) in comparison to controls; vascular endothelial growth factor was also
      up-regulated (>300 percent). In contrast, external volume expansion resulted in a
      severe inflammatory response and increased flap necrosis. CONCLUSIONS: Foam
      mediated external volume expansion improves flap survival in obese diabetic mice.
      This procedure may allow for improved clinical rates of flap survival in high
      risk patients.

PMID- 30188472
TI  - A Cost Analysis of Carpal Tunnel Release Surgery Performed Wide Awake versus
      under Sedation.
AB  - BACKGROUND: Hand surgery under local anesthesia only has been used more
      frequently in recent years. The purpose of this study was to compare
      perioperative time and cost for carpal tunnel release performed under local
      anesthesia ("wide-awake local anesthesia no tourniquet," or WALANT) only to
      carpal tunnel release performed under intravenous sedation. METHODS: A
      retrospective comparison of intraoperative (operating room) surgical time and
      postoperative (postanesthesia care unit) time for consecutive carpal tunnel
      release procedures performed under both intravenous sedation and wide-awake local
      anesthesia was undertaken. All operations were performed by the same surgeon
      using the same mini-open surgical technique. A cost analysis was performed by
      means of standardized anesthesia billing based on base units, time, and
      conversion rates. RESULTS: There were no significant differences between the two
      groups in terms of total operative time, 28 minutes in the intravenous sedation
      group versus 26 minutes in the wide-awake local anesthesia group. Postanesthesia
      care unit times were significantly longer in the intravenous sedation group (84
      minutes) compared to the wide-awake local anesthesia group (7 minutes). Depending
      on conversion rates used, a total of $139 to $432 was saved in each case
      performed with wide-awake local anesthesia by not using anesthesia services. In
      addition, a range of $1320 to $1613 was saved for the full episode of care,
      including anesthesia costs, operating room time, and postanesthesia care unit
      time for each patient undergoing wide-awake local anesthesia carpal tunnel
      release. CONCLUSION: Carpal tunnel release surgery performed with the wide-awake
      local anesthesia technique offers significant reduction in cost for use of
      anesthesia and postanesthesia care unit resources.

PMID- 30188473
TI  - Distraction Osteogenesis for Unicoronal Craniosynostosis: Rotational Flap
      Technique and Case Series.
AB  - BACKGROUND: The limitations of the soft-tissue envelope, devascularized bone
      grafts, and relapse of the deformity are important considerations in the surgical
      treatment of unicoronal craniosynostosis. The authors report their technique
      evolution of distraction osteogenesis for treatment of patients with unicoronal
      craniosynostosis. METHODS: Open anterior cranial vault reconstruction combined
      with internal distraction was used, with the aid of virtual surgical planning.
      Technique evolution included maximizing bone flap perfusion by means of limited
      rotational flap osteotomies, and preservation of dural attachments. Clinical and
      procedural characteristics including distraction protocol, intracranial volume
      change, efficiency of distraction, transfusion, operative time, length of
      hospitalization, complications, and postoperative outcomes were analyzed.
      RESULTS: Sixteen patients with nonsyndromic unicoronal craniosynostosis underwent
      repair between August of 2013 and December of 2016. Mean age was 9.0 months.
      Distractors were advanced a mean of 27.1 mm and achieved a cranial volume change
      of 29.5 percent, with a mean efficiency of 1.3 percent increase per millimeter of
      distraction. Mean operating time was 169.3 minutes. Complications were
      predominately related to infections at the distractor site. At most recent follow
      up, all patients had a Whitaker grade I result. CONCLUSIONS: Distraction
      osteogenesis can be a safe and effective method of achieving satisfactory
      aesthetic outcomes and volume expansion for patients with unicoronal
      craniosynostosis. The technique presented is proposed to maximize bone flap
      viability and limit relapse of deformity. Further long-term follow-up is needed
      for definitive comparison with traditional anterior cranial vault reconstruction.
      CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 30188474
TI  - Anatomical Nasal Lining Flaps for Closure of the Nasal Floor in Unilateral and
      Bilateral Cleft Lip Repairs Reduce Fistulas at the Alveolus.
AB  - BACKGROUND: Techniques vary for addressing the nasal floor during cleft lip
      repair in patients with a cleft lip and palate. Sometimes, no closure is
      performed, leaving a symptomatic alveolar fistula until the time of alveolar bone
      grafting. Often, medial and lateral skin flaps are used, but these are often thin
      and unreliable. Anatomical nasal lining flaps are used to improve closure with
      robust, well-vascularized flaps that anatomically close the nasal floor. METHODS:
      A retrospective chart review was performed to identify patients with a unilateral
      or bilateral cleft lip and palate who underwent primary cleft lip repair with
      nasal lining flaps or with medial and lateral flaps. The primary outcome was
      presence of a symptomatic and/or visible oronasal fistula. RESULTS: Sixty-four
      patients were included. Thirty-seven underwent closure with nasal lining flaps,
      whereas 27 underwent closure using Millard medial and lateral flaps. The rate of
      symptomatic/visible fistulas after cleft palate repair was 19 percent (seven of
      37) for patients with nasal lining flaps and 44 percent (12 of 27) for patients
      with medial and lateral flaps (p = 0.0509, Fisher's exact test). The alveolar
      fistula rate was 3 percent (one of 37) for patients with nasal lining flaps and
      30 percent (eight of 27) for patients with medial and lateral flaps (p = 0.0032,
      Fisher's exact test). CONCLUSIONS: Nasal lining flaps at the time of cleft lip
      repair effectively close the anterior nasal floor in patients with a unilateral
      or bilateral cleft lip and palate. Decreasing the presence of alveolar fistulas
      after cleft palate repair improves the quality of life for patients with cleft
      deformities. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

PMID- 30188475
TI  - Nursing Professional Development Demonstrating Value-Added Service.

PMID- 30188476
TI  - Simulation Use in Acute Care Hospitals in the United States.
AB  - Three national nursing associations formed a collaborative partnership to
      research simulation use in acute care hospitals in the United States and military
      hospitals abroad. An electronic survey was used to determine simulation
      modalities used, participants engaged, space allocation, purposes of use,
      commonly taught skills, logistics, and barriers to use. Data from 521 respondents
      revealed widespread use of a variety of simulation modalities. However, use of
      this educational strategy could be expanded to patients and families.

PMID- 30188477
TI  - Generation Z: Approaches and Teaching-Learning Practices for Nursing Professional
      Development Practitioners.

PMID- 30188478
TI  - Brief Intervention on Nurses' Knowledge and Behavior Regarding Smoking Cessation.
AB  - Nurses receive little training on smoking cessation education delivery in their
      nursing curricula and practice settings. A brief intervention to assess nurses'
      knowledge and behavior regarding smoking cessation education found increases in
      knowledge and intended behavior. In their practice setting, nurses maintained
      their knowledge long term; however, nurses did not change their behavior to match
      their intentions of increasing the delivery of smoking cessation education.

PMID- 30188479
TI  - Implementing a Resilience-Promoting Education Program for New Nursing Graduates.
AB  - Retaining qualified nurses at the bedside can have a positive impact on patient
      care safety and quality. Without support and resilience, nurses may become
      emotionally exhausted within the first year of practice. Nursing professional
      development educators must recognize that new nurses often struggle with
      stressors related to nursing and take the appropriate steps to help them build
      resilience. This article describes an education project implemented to assist new
      nurses in developing their resilience. It describes the process and outcomes of a
      resiliency training program infused into one healthcare facility's nurse
      residency program and may inform nursing professional development educators
      planning similar programs.

PMID- 30188480
TI  - Leading the Charge: Achievement of National Accreditation for a Nurse Residency
      Program.
AB  - This article describes best practice recommendations in program development for a
      nurse residency program. This registered nurse residency program is the first in
      New England to acquire the American Nurses Credentialing Center's Practice
      Transition Accreditation. Best practices identified in this effort include (a)
      use of a quality improvement analyst for data trending, (b) inclusion of an off
      shift nurse educator, (c) use of evidence-based practice, (d) a standardized
      preceptor program, and (e) appropriate evaluation instruments. New graduate nurse
      satisfaction increased and turnover decreased after program implementation.

PMID- 30188481
TI  - Nursing Professional Development Anti-Bullying Project.
AB  - This article describes a nursing professional development, evidence-based
      intervention project addressing the significant problem of bullying in the
      nursing workplace. The project entailed a 9-week, multitiered approach to teach
      behaviors to combat bullying and create the self-efficacy to do so. Results
      demonstrated statistically significant t-test comparisons of pre- and postsurvey
      measures, supporting the clinical question that empowerment and perceptual change
      drove individual and group behavior to confront bullying and create a positive
      culture shift.

PMID- 30188482
TI  - Preparing Nurse Leaders in Nursing Professional Development: Developing a Nursing
      Professional Development Department Plan.

PMID- 30188483
TI  - Providing the Evidence for Nursing Professional Development Practice:
      Highlighting a Nurse Residency Researcher.

PMID- 30188485
TI  - Preventing Preceptor Burnout Through Engagement.

PMID- 30188484
TI  - Strategies for Teaching Mindfulness Using Simulation.

PMID- 30188486
TI  - Nursing Professional Development Practitioners on Boards: A Symbiotic
      Relationship.

PMID- 30188487
TI  - An Academic Educator's View of Nursing Professional Development.

PMID- 30188489
TI  - Generation Z: Approaches and Teaching-Learning Practices for Nursing Professional
      Development Practitioners.

PMID- 30188488
TI  - The Kansas Nurse Leader Residency Program: Building Nurses' Capacity to Lead
      Change.
AB  - As nurses engage as partners in addressing complex healthcare issues, it is
      increasingly important to develop nurse leaders. Many nurses need expanded
      knowledge and training to lead change. The purpose of this article is to describe
      an innovative statewide nurse leadership residency program to prepare new nurse
      leaders in four specialty areas. Suggestions are offered for continued
      advancement of leadership training for RNs across specialty roles and settings.

PMID- 30188490
TI  - Developing Two Culture of Health Measurement Tools: Examining Employers' Efforts
      to Influence Population Health Inside and Outside Company Walls.
AB  - OBJECTIVE: To develop tools that quantify employers' investment in building
      cultures of health (COH) - inside and outside company walls. METHODS: Two COH
      instruments were developed through literature reviews and expert consultation.
      The first focused on internal culture of health (COH-INT); i.e., programs,
      policies and attributes of the physical and social environments that support
      employees' health and well-being. The second focused on external culture of
      health (COH-EXT); i.e., programs, policies, and environmental supports that
      promote communities' health. We administered these tools to 32 employers and
      examined instrument reliability, distribution of scores, and correlation between
      the two instruments. RESULTS: Both tools demonstrated adequate reliability. COH
      INT and COH-EXT scores changed minimally over the 3-year study timeframe. There
      was little correlation between the COH-INT and COH-EXT scores. CONCLUSIONS: More
      research is needed to further develop and validate COH-EXT instruments.

PMID- 30188492
TI  - Evaluation of a Lifestyle Change Worksite Weight Management Program Across
      Multiple Employers and Sites.
AB  - OBJECTIVE: To assess weight loss outcomes among participants (N = 1,090) of a
      weight management program across multiple worksites (N = 10) in a retrospective
      analysis. METHODS: Weekly classes focused on diet, exercise and behavior change.
      One employer provided incentives for weight loss and two incentivized weight loss
      and class attendance. RESULTS: Mean weight loss (N = 1,090; 79.3% female) was 
      2.9% (SD = 3.0%). Average number of classes attended was 6.87/10 (SD = 2.9) and
      was significantly correlated with percent weight change (r = -0.46; p < .001).
      Participants incentivized for attendance attended significantly more classes (M =
      7.5, SD = 2.8) than did those not so incentivized (M = 6.4, SD = 2.9, p < .001),
      but did not lose more weight (p = .24). Participants incentivized for weight loss
      did not lose significantly more weight than those not so incentivized (p = .26).
      CONCLUSIONS: These data support the effectiveness of this worksite program.
      Utilizing incentives to promote class attendance may be beneficial for increasing
      engagement in similar programs.

PMID- 30188491
TI  - Estimating the Impact of Diabetes Mellitus on Worker Productivity Using Self
      Report, Electronic Health Record and Human Resource Data.
AB  - OBJECTIVE: We assessed the relationship between diabetes mellitus (DM) and
      measures of worker productivity, direct health care costs, and costs associated
      with lost productivity (LP) among health care industry workers across two
      integrated health care systems. METHODS: We used data from the Value Based
      Benefit Design Health and Wellness Study Phase II (VBD), a prospective study of
      employees surveyed across health systems. Survey and health care utilization data
      were linked to estimate LP and health care utilization costs. RESULTS: Mean
      marginal lost productive time per week was 0.56 hours higher for respondents with
      DM. Mean adjusted monthly total health care utilization costs were $467 higher
      for respondents with DM. CONCLUSION: The impact of DM is reflected in higher
      rates of LP and higher indirect costs for employers related to LP and higher
      health care resource use.

PMID- 30188493
TI  - The Relationships between Physical Activity and Cardiometabolic Risk Factors
      Among Women Participating in a University-Based Worksite Wellness Program.
AB  - OBJECTIVE: Associations between changes in physical activity (PA) and
      cardiometabolic risk factors among women with overweight/obesity enrolled in a
      university-based worksite wellness program (WWP) were examined. METHODS: Data
      from 173 women who completed a 26-week WWP were analyzed retrospectively.
      Participants completed diet and PA assessments and received client-centered
      diet/lifestyle counseling at baseline, and 12 and 26-weeks thereafter.
      Anthropometrics, blood pressure and total cholesterol were measured; PA was self
      reported using the International Physical Activity Questionnaire-short form at
      each visit. RESULTS: Significant improvements in anthropometrics (P < 0.001),
      blood pressure (P < 0.001), total cholesterol (P = 0.014), and PA (P = 0.007)
      were found at 26-weeks. In adjusted linear regression models, a 10-metabolic
      equivalent-minute increase in PA was associated with 0.01% corresponding
      decreases in weight and waist circumference. CONCLUSIONS: Among women who
      completed this WWP, increased PA was associated with reductions in anthropometric
      measures.

PMID- 30188494
TI  - Experimental Woodsmoke Exposure During Exercise and Blood Oxidative Stress.
AB  - OBJECTIVES: The current laboratory study quantified blood oxidative stress to
      woodsmoke exposure. METHODS: Participants inhaled woodsmoke during three
      randomized crossover exercise trials (Clean Air [0 MUg/m], Low Exposure [250
      MUg/m], and High Exposure [500 MUg/m], Woodsmoke [particulate matter less than
      2.5 MUm, PM2.5]). Trolox equivalent antioxidant capacity (TEAC), uric acid (UA),
      8-isoprostanes (8-ISO), lipid hydroperoxides (LOOH), protein carbonyls (PC),
      nitrotyrosine (3-NT), 8-isoprostane, and myeloperoxidase (MPO) were quantified in
      Pre, immediately Post, and 1- (1Hr) hour post blood samples. RESULTS: UA
      decreased following Low Exposure, while plasma TEAC levels increased Post and
      1Hr. LOOH levels decreased 1Hr Post (High Exposure), while 8-Iso increased
      following both smoke trials. PC and MPO were unchanged following all trials,
      while 3-NT increased over Clean Air. CONCLUSION: Blood oxidative stress occurred
      largely independent of PM2.5 concentrations. Future studies should employ longer
      duration smoke and exercise combined with physiologic parameters.

PMID- 30188495
TI  - Effects of Wrist Cooling on Recovery From Exercise-Induced Heat Stress With
      Firefighting Personal Protective Equipment.
AB  - OBJECTIVE: To determine the effects of wrist cooling on recovery from exercise
      induced heat stress (EIHS) from wearing firefighting personal protective
      equipment (PPE) and self-contained breathing apparatus. METHODS: Using a single
      blind, counterbalanced, crossover-design, in 11 healthy men, we measured heart
      rate (HR), HR variability (HRV), core temperature (TCore), thermal strain (TS),
      and fatigue at rest, during 30-minute of exercise in PPE+SCBA, and during
      recovery while wearing a wrist cooling band (control[off] vs cool[on]). RESULTS:
      No differences were observed between trials at baseline or during exercise, in
      HR, TCore, TS, or fatigue. Time to 50% and recovery were not different between
      trials. Upon recovery, TCore was lower, while HR, fatigue, HRV, and TS were
      relatively indifferent with cooling. CONCLUSION: Wrist cooling after EIHS only
      modestly enhanced recovery, questioning its implementation during on-scene
      rehabilitation of firefighters.

PMID- 30188499
TI  - Mesenchymal stem cells transplantation attenuates brain injury and enhances
      bacterial clearance in Escherichia coli meningitis in newborn rats.
AB  - OBJECTIVE: Neonatal meningitis caused by Escherichia coli results in significant
      mortality and neurological disabilities, with few effective treatments. Recently,
      we demonstrated that human umbilical cord blood-derived mesenchymal stem cell
      (hUCB-MSC) transplantation attenuated E. coli-induced severe pneumonia, primarily
      by reducing inflammation and enhancing bacterial clearance. This study aimed to
      determine whether intraventricular transplantation of hUCB-MSCs attenuated the
      brain injury in E. coli meningitis in newborn rats. METHODS: Meningitis without
      concomitant bacteremia was induced by intraventricular injection of 5 * 102
      colony forming units of K1 (-) E. coli in rats at postnatal day (P)11, and hUCB
      MSCs (1 * 105) were transplanted intraventricularly 6 h after induction of
      meningitis. Antibiotics was started 24 h after modeling. RESULT: Meningitis
      modeling induced robust proliferation of E. coli in the cerebrospinal fluid and
      increased mortality in rat pups, and MSC transplantation significantly reduced
      this bacterial growth and the mortality rate. Impaired sensorimotor function in
      the meningitis rats was ameliorated by MSCs injection. MSCs transplantation also
      attenuated meningitis caused brain injury including cerebral ventricular
      dilatation, brain cell death, reactive gliosis, and inflammatory response.
      CONCLUSION: Intraventricular transplantation of hUCB-MSCs significantly improved
      survival and attenuated the brain injury via anti-inflammatory and antibacterial
      effects in experimental neonatal E. coli meningitis.

PMID- 30188498
TI  - Bone status in relation to ambulatory performance in girls with Rett syndrome: a
      10-year longitudinal study.
AB  - BACKGROUND: Low bone mass is a frequent and early complication of girls with Rett
      syndrome. As a consequence of the low bone mass, Rett patients are at an
      increased risk of fragility fractures. This study aimed to investigate the long
      term influences of mobility on bone status in girls with Rett syndrome. METHODS:
      In 58 girls with Rett syndrome, biochemical parameters and quantitative
      ultrasound parameters at phalanges (amplitude-dependent speed of sound: AD-SoS
      and bone transmission time: BTT) were measured at baseline and after 5 and 10
      years. The subjects were divided into two groups: nonambulatory (n = 28) and
      ambulatory (n = 30). RESULTS: In nonambulatory Rett subjects, the values of AD
      SoS and BTT were significantly lower than in ambulatory Rett subjects at each
      time point. However, during the 10-year follow-up both ambulatory and
      nonambulatory Rett patients showed a similar worsening in their bone status.
      CONCLUSION: This longitudinal study suggests that both ambulatory and
      nonambulatory Rett subjects present a progressive deterioration of bone status as
      assessed by quantitative ultrasound parameters, and the ambulatory impairment and
      the nutritional status seem to play a key role in the deterioration of bone
      status.

PMID- 30188497
TI  - Prediction of ROP Treatment and Evaluation of Screening Criteria in VLBW Infants
      a Population Based Analysis.
AB  - BACKGROUND: The incidence of retinopathy of prematurity (ROP) and ROP screening
      criteria differ between countries. We assessed whether ROP screening could be
      reduced based on the local ROP incidence. METHODS: Observational cohort study of
      infants born in Switzerland between 2006 and 2015 <32 0/7 weeks. Chronological
      and postmenstrual ages at ROP treatment were analyzed. A model to identify ROP
      treatment on patients born between 2006 and 2012 (training set) was developed and
      tested on patients born between 2013 and 2015 (validation set). RESULTS: Of 7817
      live-born infants, 1098 died within the first 5 weeks of life. The remaining 6719
      infants were included into analysis. All patients requiring ROP treatment would
      have been identified if screening had been performed before reaching 60 days of
      life or 37 3/7 weeks postmenstrual age, whichever came first. The training and
      validation sets included 4522 and 2197 preterm infants encompassing 56 and 20
      patients receiving ROP treatment, respectively. All patients would have required
      screening to reach 100% sensitivity. To reach a sensitivity of 95.0% and a
      specificity of 87.6%, we predicted a reduction in 13.2% of patients requiring
      screening (c-statistic = 0.916). CONCLUSIONS: A substantial reduction of infants
      requiring screening seems possible, but necessitates prospective testing of new
      screening criteria.

PMID- 30188500
TI  - Early human brain development: insights into macroscale connectome wiring.
AB  - BACKGROUND: Early brain development is closely dictated by distinct
      neurobiological principles. Here, we aimed to map early trajectories of
      structural brain wiring in the neonatal brain. METHODS: We investigated
      structural connectome development in 44 newborns, including 23 preterm infants
      and 21 full-term neonates scanned between 29 and 45 postmenstrual weeks.
      Diffusion-weighted imaging data were combined with cortical segmentations derived
      from T2 data to construct neonatal connectome maps. RESULTS: Projection fibers
      interconnecting primary cortices and deep gray matter structures were noted to
      mature faster than connections between higher-order association cortices
      (fractional anisotropy (FA) F = 58.9, p < 0.001, radial diffusivity (RD) F =
      28.8, p < 0.001). Neonatal FA-values resembled adult FA-values more than RD,
      while RD approximated the adult brain faster (F = 358.4, p < 0.001). Maturational
      trajectories of RD in neonatal white matter pathways revealed substantial overlap
      with what is known about the sequence of subcortical white matter myelination
      from histopathological mappings as recorded by early neuroanatomists (mean RD 68
      regions r = 0.45, p = 0.008). CONCLUSION: Employing postnatal neuroimaging we
      reveal that early maturational trajectories of white matter pathways display
      discriminative developmental features of the neonatal brain network. These
      findings provide valuable insight into the early stages of structural connectome
      development.

PMID- 30188502
TI  - A family of NICU graduates!

PMID- 30188501
TI  - Early body composition changes are associated with neurodevelopmental and
      metabolic outcomes at 4 years of age in very preterm infants.
AB  - BACKGROUND: Very preterm (VPT) infants are at-risk for altered growth, slower
      speed of processing (SOP), and hypertension. This study assesses the relationship
      between postnatal body composition (BC), neurodevelopment (indexed by SOP), and
      blood pressure (BP) in VPT infants. METHODS: Thirty-four VPT infants underwent
      weekly measurements and BC testing until discharge and post-discharge at 4 mos
      CGA and 4 yrs. At post-discharge visits, SOP was assessed using visual evoked
      potentials and the NIH Toolbox; BP was also measured. RESULTS: In-hospital rate
      of weight, length and fat-free mass (FFM) gains were associated with faster SOP
      at 4 yrs. Higher rate of gains in weight and FFM from discharge to 4 mos CGA were
      associated with faster SOP at 4 mos CGA, while higher fat mass (FM) gains during
      the same time were positively associated with BP at 4 yrs. BC at 4 yrs nor gains
      beyond 4 mos CGA were associated with outcomes. CONCLUSIONS: In VPT infants,
      early FFM gains are associated with faster SOP, whereas post-discharge FM gains
      are associated with higher BPs at 4 yrs. This shows birth to 4 mos CGA is a
      sensitive period for growth and its relation to neurodevelopmental and metabolic
      outcomes. Close monitoring and early nutritional adjustments to optimize quality
      of gains may improve outcomes.

PMID- 30188504
TI  - The definition of bronchopulmonary dysplasia: an evolving dilemma.
AB  - The definition of bronchopulmonary dysplasia (BPD) continues to be a challenging
      one. The evolution of the disease as well as its definition are discussed.
      Limitations of the current as well as newer suggested definitions of BPD are
      summarized. Recognition of the variability of the pulmonary phenotype is a
      critical aspect of the disease that needs to identified, utilizing biomarkers
      that will potentially better inform the next iteration of the definition of BPD.

PMID- 30188496
TI  - Acceleration of electrons in the plasma wakefield of a proton bunch.
AB  - High-energy particle accelerators have been crucial in providing a deeper
      understanding of fundamental particles and the forces that govern their
      interactions. To increase the energy of the particles or to reduce the size of
      the accelerator, new acceleration schemes need to be developed. Plasma wakefield
      acceleration1-5, in which the electrons in a plasma are excited, leading to
      strong electric fields (so called 'wakefields'), is one such promising
      acceleration technique. Experiments have shown that an intense laser pulse6-9 or
      electron bunch10,11 traversing a plasma can drive electric fields of tens of
      gigavolts per metre and above-well beyond those achieved in conventional radio
      frequency accelerators (about 0.1 gigavolt per metre). However, the low stored
      energy of laser pulses and electron bunches means that multiple acceleration
      stages are needed to reach very high particle energies5,12. The use of proton
      bunches is compelling because they have the potential to drive wakefields and to
      accelerate electrons to high energy in a single acceleration stage13. Long, thin
      proton bunches can be used because they undergo a process called self
      modulation14-16, a particle-plasma interaction that splits the bunch
      longitudinally into a series of high-density microbunches, which then act
      resonantly to create large wakefields. The Advanced Wakefield (AWAKE) experiment
      at CERN17-19 uses high-intensity proton bunches-in which each proton has an
      energy of 400 gigaelectronvolts, resulting in a total bunch energy of 19
      kilojoules-to drive a wakefield in a ten-metre-long plasma. Electron bunches are
      then injected into this wakefield. Here we present measurements of electrons
      accelerated up to two gigaelectronvolts at the AWAKE experiment, in a
      demonstration of proton-driven plasma wakefield acceleration. Measurements were
      conducted under various plasma conditions and the acceleration was found to be
      consistent and reliable. The potential for this scheme to produce very high
      energy electron bunches in a single accelerating stage20 means that our results
      are an important step towards the development of future high-energy particle
      accelerators21,22.

PMID- 30188505
TI  - Commentary on "Childhood cardiovascular health and subfertility: The Bogalusa
      Heart Study".

PMID- 30188503
TI  - Time-restricted feeding causes irreversible metabolic disorders and gut
      microbiota shift in pediatric mice.
AB  - BACKGROUND: Time-restricted feeding regimen (TRF), that is, no food consumption
      for 14-16 h during the light phase per day, attenuates the fattening traits and
      metabolic disorders in adults. This study aims to further investigate whether TRF
      would be protective against similar nutritional challenges in juvenile mice.
      METHODS: Mice in the experimental group were treated with TRF during the first 4
      weeks (considered to be the childhood phase of mice) before switching to ad
      libitum (AD) feeding pattern as adults; the control group with all subjects
      sticks to AD mode. Body weight was monitored, and serum biochemistry, sexual
      maturity, immune function, and gut microbiota were assessed at a certain timing.
      RESULTS: Mice treated with TRF during the childhood period (from weaning age) but
      went through AD feeding pattern as adults demonstrated the tendency of higher
      body weight, higher levels of serum glucose, shrunken Langerhans islets, fatty
      liver disease, thickening of aortic walls, delayed sexual development, increased
      proportion of T regulatory cells, and unhealthy gut microbiota. CONCLUSION:
      Childhood TRF causes pleiotropic adverse effects, including severe irreversible
      metabolic disorders, depressed immune function, and retarded puberty. Microbiota
      set the stage for TRF to employ downstream reactions on the above changes.

PMID- 30188506
TI  - Policy threats to maternal and child nutrition: putting the unborn child at a
      lifelong disadvantage.

PMID- 30188507
TI  - Commentary from the pediatric policy council 2018: the year of living dizzyingly.

PMID- 30188508
TI  - Sarcomere gene variants act as a genetic trigger underlying the development of
      left ventricular noncompaction.
AB  - BACKGROUND: Left ventricular noncompaction (LVNC) is a primary cardiomyopathy
      with heterogeneous genetic origins. The aim of this study was to elucidate the
      role of sarcomere gene variants in the pathogenesis and prognosis of LVNC.
      METHODS AND RESULTS: We screened 82 Japanese patients (0-35 years old), with a
      diagnosis of LVNC, for mutations in seven genes encoding sarcomere proteins, by
      direct DNA sequencing. We identified variants in a significant proportion of
      cases (27%), which were associated with poor prognosis (p = 0.012), particularly
      variants in TPM1, TNNC1, and ACTC1 (p = 0.012). To elucidate the pathological
      role, we developed and studied human-induced pluripotent stem cells (hiPSCs) from
      a patient carrying a TPM1 p.Arg178His mutation, who underwent heart
      transplantation. These cells displayed pathological changes, with mislocalization
      of tropomyosin 1, causing disruption of the sarcomere structure in
      cardiomyocytes, and impaired calcium handling. Microarray analysis indicated that
      the TPM1 mutation resulted in the down-regulation of the expression of numerous
      genes involved in heart development, and positive regulation of cellular process,
      especially the calcium signaling pathway. CONCLUSIONS: Sarcomere genes are
      implicated as genetic triggers in the development of LVNC, regulating the
      expression of numerous genes involved in heart development, or modifying the
      severity of disease.

PMID- 30188509
TI  - Maternal immune activation: reporting guidelines to improve the rigor,
      reproducibility, and transparency of the model.
AB  - The 2017 American College of Neuropychopharmacology (ACNP) conference hosted a
      Study Group on 4 December 2017, Establishing best practice guidelines to improve
      the rigor, reproducibility, and transparency of the maternal immune activation
      (MIA) animal model of neurodevelopmental abnormalities. The goals of this session
      were to (a) evaluate the current literature and establish a consensus on best
      practices to be implemented in MIA studies, (b) identify remaining research gaps
      warranting additional data collection and lend to the development of evidence
      based best practice design, and (c) inform the MIA research community of these
      findings. During this session, there was a detailed discussion on the importance
      of validating immunogen doses and standardizing the general design (e.g.,
      species, immunogenic compound used, housing) of our MIA models both within and
      across laboratories. The consensus of the study group was that data does not
      currently exist to support specific evidence-based model selection or
      methodological recommendations due to lack of consistency in reporting, and that
      this issue extends to other inflammatory models of neurodevelopmental
      abnormalities. This launched a call to establish a reporting checklist focusing
      on validation, implementation, and transparency modeled on the ARRIVE Guidelines
      and CONSORT (scientific reporting guidelines for animal and clinical research,
      respectively). Here we provide a summary of the discussions in addition to a
      suggested checklist of reporting guidelines needed to improve the rigor and
      reproducibility of this valuable translational model, which can be adapted and
      applied to other animal models as well.

PMID- 30188510
TI  - Neuropsychopharmacology (NPP): gender balance in journal function.

PMID- 30188511
TI  - Interactive effects between hemizygous 15q13.3 microdeletion and peripubertal
      stress on adult behavioral functions.
AB  - 15q13.3 microdeletion is one of several gene copy number variants (CNVs)
      conferring increased risk of psychiatric and neurological disorders. This
      microdeletion gives rise to a variable spectrum of pathological phenotypes,
      ranging from asymptomatic to severe clinical outcomes. The reasons for these
      varying phenotypic outcomes remain unknown. Using a mouse model of hemizygous
      deletion of the orthologous region of 15q13.3, the present study examined whether
      exposure to stressful life events might interact with hemizygous 15q13.3
      microdeletion in the development of behavioral dysfunctions. We show that
      hemizygous 15q13.3 microdeletion alone induces only limited effects on adult
      behaviors, but when combined with psychological stress in pubescence (postnatal
      days 30-40), it impairs sensorimotor gating and increases the sensitivity to the
      psychostimulant drug, amphetamine, at adult age. Stress exposure in adolescence
      (postnatal days 50-60) did not induce similar interactions with 15q13.3
      microdeletion, but led to impaired emotional learning and memory and social
      behavior regardless of the genetic background. The present study provides the
      first evidence for interactive effects between hemizygous 15q13.3 microdeletion
      and exposure to stressful life events, and at the same time, it emphasizes an
      important influence of the precise timing of postnatal stress exposure in these
      interactions. Our findings suggest that hemizygous 15q13.3 microdeletion can act
      as a "disease primer" that increases the carrier's vulnerability to the
      detrimental effects of peripubertal stress exposure on adult behaviors.

PMID- 30188512
TI  - Effects of sedative drug use on the dopamine system: a systematic review and meta
      analysis of in vivo neuroimaging studies.
AB  - Use of alcohol, cannabis and opioids is highly prevalent and is associated with
      global disease burden and high economic costs. The exact pathophysiology of abuse
      or addiction associated with these sedative substances is not completely
      understood, but previous research implicates the important role of the striatal
      dopamine system in the addiction process. Multiple studies investigated changes
      in the striatal dopamine systems of users of sedative substances, but currently
      these results are very heterogeneous. Therefore, we conducted a meta-analysis of
      in vivo neuroimaging studies investigating dopaminergic alterations in the
      striatum of users of alcohol, opioids or cannabis. Analyses for each substance
      were conducted separately for the availability of D2/D3 dopamine receptors,
      dopamine transporters and dopamine synthesis capacity. In total, 723 substance
      users and 752 healthy controls were included. The results indicated a significant
      lower striatal D2/D3 receptor availability in alcohol users compared to controls
      (g = 0.46) but no difference in dopamine transporter availability or dopamine
      synthesis capacity. Our analysis indicated that changes of dopamine receptors and
      transporters are moderated by the duration of abstinence. Comparing opioid users
      with controls revealed a significant lower D2/D3 receptor availability (g = 1.17)
      and a significantly lower transporter availability (g = 1.55) in opioid users.
      For cannabis users, there was no significant difference in receptor availability
      compared to controls and too few studies provided information on dopamine
      transporter availability or synthesis capacity. Our analysis provides strong
      evidence for a central role of the striatal dopamine system in use of alcohol or
      opioids. Further studies are needed to clarify the impact of the dopamine system
      in cannabis users.

PMID- 30188513
TI  - Early life stress leads to sex differences in development of depressive-like
      outcomes in a mouse model.
AB  - Childhood trauma and neglect influence emotional development and increase the
      risk for and severity of mental illness. Women have a heightened susceptibility
      to the effects of early life stress (ELS) and are twice as likely as men to
      develop debilitating, stress-associated disorders later in life, such as major
      depressive disorder (MDD). Until now, mouse models of depression have been
      largely unsuccessful at replicating the diverse symptomatology of this disease
      and the sex bias in vulnerability. From P4 to P11, a limited bedding model that
      leads to fragmented maternal care, was used to induce ELS. Early adolescent and
      young adult mice were tested on an array of assays to test for depressive-like
      behavior. This included our newly developed automated home cage behavioral
      recognition system, where the home cage behavior of ELS and control mice could be
      monitored over a continuous 5-10 day span. ELS females, but not males, exhibited
      depressive-like behaviors on traditional assays. These effects emerged during
      adolescence and became more severe in adulthood. Using the novel home cage video
      monitoring method, we identified robust and continuous markers of depressive-like
      pathology in ELS females that phenocopy many of the behavioral characteristics of
      depression in humans. ELS effects on home cage behavior were rapidly rescued by
      ketamine, a fast-acting antidepressant. Together, these findings highlight that
      limited bedding ELS (1) produces an early emerging, female-specific depressive
      phenotype that responds to a fast-acting antidepressant and (2) this model has
      the potential to inform sex-selective risk for the development of stress-induced
      mental illness.

PMID- 30188514
TI  - Food addiction: a valid concept?
AB  - Can food be addictive? What does it mean to be a food addict? Do common
      underlying neurobiological mechanisms contribute to drug and food addiction?
      These vexing questions have been the subject of considerable interest and debate
      in recent years, driven in large part by the major health concerns associated
      with dramatically increasing body weights and rates of obesity in the United
      States, Europe, and other regions with developed economies. No clear consensus
      has yet emerged on the validity of the concept of food addiction and whether some
      individuals who struggle to control their food intake can be considered food
      addicts. Some, including Fletcher, have argued that the concept of food addiction
      is unsupported, as many of the defining features of drug addiction are not seen
      in the context of feeding behaviors. Others, Kenny included, have argued that
      food and drug addiction share similar features that may reflect common underlying
      neural mechanisms. Here, Fletcher and Kenny argue the merits of these opposing
      positions on the concept of food addiction.

PMID- 30188516
TI  - Effects of long-term high-fat food or methamphetamine intake and serotonin 2C
      receptors on reversal learning in female rhesus macaques.
AB  - Perseverative behavior has been highly implicated in addiction. Activation of
      serotonin 2C receptors (5-HT2CRs) attenuates cocaine and high caloric food
      intake, but whether a 5-HT2CR agonist can reduce high caloric diet (HCD) or
      methamphetamine (METH) intake and response perseveration remains unknown.
      Clarifying the role of 5-HT2CRs in these behaviors will improve knowledge of
      neurochemical processes that regulate flexible decision-making and whether
      improvements in decision-making are accompanied by decreases in HCD or METH
      intake. This study evaluated the effects of long-term HCD and METH intake on
      reversal learning in female rhesus monkeys. The effects of the 5-HT2CR agonist
      WAY163909 on reversal learning before and after extended HCD or METH intake, and
      on food intake, was also tested. Moreover, we examined whether the 5-HT2CR is
      necessary for the effects of WAY163909. WAY163909 was given prior to reversal
      learning at baseline and after extended HCD or METH intake, and prior to measures
      of food intake. Extended intake of METH or the HCD increased perseverative errors
      during reversal. WAY163909 increased correct responses and decreased
      perseverative errors, both before and after extended HCD or METH intake.
      Similarly, WAY163909 decreased consumption of a HCD, but not a low caloric diet.
      The effects of WAY163909 on all these measures were blocked by co-administration
      with a 5-HT2CR antagonist. These data indicate that long-term HCD or METH intake
      disrupts flexible decision-making. Further, the results suggest that reductions
      in food intake produced by WAY163909 are associated with parallel improvements in
      decision-making strategies, underscoring the role of the 5-HT2CR for these
      behavioral effects.

PMID- 30188515
TI  - PET imaging reveals lower kappa opioid receptor availability in alcoholics but no
      effect of age.
AB  - Opioid receptors are implicated in alcoholism, other addictions, withdrawal, and
      depression, and are considered potential pharmacological targets for treatment.
      Our goal in the present study was to compare the availability of kappa opioid
      receptors (KOR) between an alcohol-dependent cohort (AD) and a healthy control
      cohort (HC). Sixty-four participants-36 AD and 28 HC-underwent PET scans with
      [11C]LY2795050, a selective kappa antagonist tracer. Partial-volume correction
      was applied to all PET data to correct for atrophy. Volume of distribution (VT)
      of the tracer was estimated regionally as a measure of KOR availability. VT
      values of AD versus HC were compared for 15 defined ROIs. Multivariate analysis
      showed a main effect of group on VT across these 15 ROIs. Post hoc tests showed
      that AD had significantly lower VT and thus a lower KOR availability than HC in
      amygdala and pallidum (corrected for multiple comparisons). Exploratory analysis
      of change in VT with age was conducted; VT was not found to vary significantly
      with age in any region. Our findings of lower VT in AD versus HC in multiple
      regions are in contrast to findings in the mu and delta opioid receptor systems
      of higher VT in AD versus HC. Although age-related decline in receptors has
      previously been observed in the mu opioid receptor system, we found that KOR
      availability does not change with age.

PMID- 30188518
TI  - Gene-edited plants cross European event horizon.

PMID- 30188520
TI  - Around the world in a month.

PMID- 30188519
TI  - Verily project releases millions of factory-reared mosquitoes.

PMID- 30188521
TI  - Brain leaks and consumer neurotechnology.

PMID- 30188517
TI  - Glycogen synthase kinase 3 beta regulates ethanol consumption and is a risk
      factor for alcohol dependence.
AB  - Understanding how ethanol actions on brain signal transduction and gene
      expression lead to excessive consumption and addiction could identify new
      treatments for alcohol dependence. We previously identified glycogen synthase
      kinase 3-beta (Gsk3b) as a member of a highly ethanol-responsive gene network in
      mouse medial prefrontal cortex (mPFC). Gsk3b has been implicated in dendritic
      function, synaptic plasticity and behavioral responses to other drugs of abuse.
      Here, we investigate Gsk3b in rodent models of ethanol consumption and as a risk
      factor for human alcohol dependence. Stereotactic viral vector gene delivery
      overexpression of Gsk3b in mouse mPFC increased 2-bottle choice ethanol
      consumption, which was blocked by lithium, a known GSK3B inhibitor. Further,
      Gsk3b overexpression increased anxiety-like behavior following abstinence from
      ethanol. Protein or mRNA expression studies following Gsk3b over-expression
      identified synaptojanin 2, brain-derived neurotrophic factor and the neuropeptide
      Y Y5 receptor as potential downstream factors altering ethanol behaviors. Rat
      operant studies showed that selective pharmacologic inhibition of GSK3B with TDZD
      8 dose-dependently decreased motivation to self-administer ethanol and sucrose
      and selectively blocked ethanol relapse-like behavior. In set-based and gene-wise
      genetic association analysis, a GSK3b-centric gene expression network had
      significant genetic associations, at a gene and network level, with risk for
      alcohol dependence in humans. These mutually reinforcing cross-species findings
      implicate GSK3B in neurobiological mechanisms controlling ethanol consumption,
      and as both a potential risk factor and therapeutic target for alcohol
      dependence.

PMID- 30188522
TI  - Erratum: Repair of double-strand breaks induced by CRISPR-Cas9 leads to large
      deletions and complex rearrangements.

PMID- 30188523
TI  - Q218-public flotation jackpot.

PMID- 30188525
TI  - Top 20 translational researchers of 2017.

PMID- 30188526
TI  - PODCAST: First rounders: Feng Zhang.

PMID- 30188524
TI  - EU court casts new plant breeding techniques into regulatory limbo.

PMID- 30188527
TI  - Personalized postdoctoral fellowship care.

PMID- 30188528
TI  - EvolvR-ing to targeted mutagenesis.

PMID- 30188529
TI  - Small molecules get the message.

PMID- 30188530
TI  - Erratum: Comprehensive multi-center assessment of small RNA-seq methods for
      quantitative miRNA profiling.

PMID- 30188533
TI  - Analyzing the protection scope limit for biosequence patent claims in China.

PMID- 30188535
TI  - A triumph of perseverance over interference.

PMID- 30188532
TI  - Erratum: Human embryonic stem cell-derived cardiomyocytes restore function in
      infarcted hearts of non-human primates.

PMID- 30188534
TI  - A case of mistaken identity.

PMID- 30188536
TI  - Live bacterial biotherapeutics in the clinic.

PMID- 30188538
TI  - Recent patents in epigenetics.

PMID- 30188537
TI  - Sangamo poised for CAR-Treg race.

PMID- 30188540
TI  - FDA approves first single-dose antimalarial.

PMID- 30188541
TI  - Genomes for all.

PMID- 30188539
TI  - Deep learning in biomedicine.
AB  - Deep learning is beginning to impact biological research and biomedical
      applications as a result of its ability to integrate vast datasets, learn
      arbitrarily complex relationships and incorporate existing knowledge. Already,
      deep learning models can predict, with varying degrees of success, how genetic
      variation alters cellular processes involved in pathogenesis, which small
      molecules will modulate the activity of therapeutically relevant proteins, and
      whether radiographic images are indicative of disease. However, the flexibility
      of deep learning creates new challenges in guaranteeing the performance of
      deployed systems and in establishing trust with stakeholders, clinicians and
      regulators, who require a rationale for decision making. We argue that these
      challenges will be overcome using the same flexibility that created them; for
      example, by training deep models so that they can output a rationale for their
      predictions. Significant research in this direction will be needed to realize the
      full potential of deep learning in biomedicine.

PMID- 30188543
TI  - Alnylam launches era of RNAi drugs.

PMID- 30188544
TI  - A call for science-based review of the European court's decision on gene-edited
      crops.

PMID- 30188545
TI  - Biocon's target factory.

PMID- 30188546
TI  - Smallpox antiviral ends decades-long search.

PMID- 30188547
TI  - In silico farming drives next wave in agriculture.

PMID- 30188548
TI  - Roche splashes $2.4 billion on Foundation Medicine's cancer platform.

PMID- 30188549
TI  - Erratum: Strength in numbers from integrated single-cell neuroscience.

PMID- 30188550
TI  - Multiplex detection of urinary miRNA biomarkers by transmission surface plasmon
      resonance.
AB  - The clinical assessment of short-stranded nucleic acid biomarkers such as miRNAs
      could potentially provide useful information for monitoring disease progression,
      prompting definitive treatment decisions. In the past decade, advancements in
      biosensing technology have led to a shift towards rapid, real-time and label-free
      detection systems; as such, surface plasmon resonance (SPR) biosensor-based
      technology has become of high interest. Here, we developed an automated multiplex
      transmissive surface plasmon resonance (t-SPR) platform with the use of a capped
      gold nanoslit integrated microfluidic surface plasmon resonance (SPR) biosensor.
      The automated platform was custom designed to allow the analysis of spectral
      measurements using wavelength shift (dlambda), intensity (dI) and novel area
      change (dA) for surface binding reactions. A simple and compact nanostructure
      based biosensor was fabricated with multiplex real-time detection capabilities.
      The sensitivity and specificity of the microfluidic device was demonstrated
      through the use of functionalised AuNPs for target molecule isolation and signal
      enhancement in combination with probes on the CG nanoslit surface. Our work
      allows for the multiplex detection of miRNA at femtomolar concentrations in
      complex media such as urine.

PMID- 30188551
TI  - Facile synthesis of tin-doped mayenite electride composite as a non-noble metal
      durable electrocatalyst for oxygen reduction reaction (ORR).
AB  - In this study, we synthesized nanosized Sn-doped C12A7:e- (C12Al7-xSnx:e-, where
      x = 0.20 to 1) composite with high surface area of 244 m2 g-1. An increasing
      trend in conductivity of Sn-doped C12A7:e- composites was observed at 300 K: 24 S
      cm-1, 68 S cm-1, 190 S cm-1 and 290 S cm-1, at doping levels of x = 0.20, 0.40,
      0.80, and 1, respectively. Sn-doped C12A7:e-, with and without reduced graphene
      oxide (rGO), acts as a less expensive and highly active and durable
      electrocatalyst in the oxygen reduction reaction (ORR) for fuel cells. In the
      case of C12A7-xSnx:e- (where x = 1), calculated onset potential and current
      density were comparable to the commercially available 20% Pt/C electrode.
      Moreover, significant improvement was observed for Sn-doped C12A7:e- (doping
      level x = 1) with rGO composite. The ORR current density was about 5.9 mA cm-2,
      which was higher than that of Pt/C (5.2 mA cm-2). Our investigation of the effect
      of cation doping on structural and electrical properties of Sn-doped C12A7:e-
      composites shows that these results manifested the feasibility of this sol-gel
      method for different element doping. Furthermore, the as-prepared promising non
      noble metal catalysts (NNMCs), viz., Sn-doped C12A7:e- composite materials,
      possess intrinsic long-time stability and excellent methanol resistance toward
      ORR in alkaline media and may serve as a promising alternative to Pt/C materials
      for ORR in its widespread implementation in fuel cells.

PMID- 30188552
TI  - On-the-fly kinetics of hydrogen abstraction from polycyclic aromatic hydrocarbons
      by methyl/ethyl radicals.
AB  - This work provides a rigorous procedure, within the framework of the Reaction
      Class Transition State Theory (RC-TST) and the Structure-Activity Relationship
      (SAR), for predicting reliable thermal rate constants on-the-fly for hydrogen
      abstraction reactions by methyl/ethyl radicals from Polycyclic Aromatic
      Hydrocarbons (PAHs) in a temperature range of 300-3000 K. All necessary RC-TST
      parameters were derived from ab initio calculations for a representative set of
      36 reactions on which different error analyses and comparisons with available
      literature data were carried out. In addition to the good agreement between the
      RC-TST rate constants and the literature data, the detailed error analyses show
      that RC-TST/SAR, utilizing either the Linear Energy Relationship (LER) where only
      the reaction energy is needed or Barrier Height Grouping (BHG) where no
      additional data is needed, can predict the thermal rate constants for any
      reaction in the title reaction class with an average systematic error of less
      than 50% when compared to the explicit rate calculations. Therefore, the
      constructed RC-TST procedure can be confidently used to obtain reliable rate
      constants on the fly in an attempt to effectively construct detailed kinetic
      mechanisms for PAH-related fuels.

PMID- 30188554
TI  - Proanthocyanidin B2 attenuates postprandial blood glucose and its inhibitory
      effect on alpha-glucosidase: analysis by kinetics, fluorescence spectroscopy,
      atomic force microscopy and molecular docking.
AB  - As a dimer of proanthocyanidin, proanthocyanidin B2 (PB2) was found to
      effectively attenuate postprandial blood glucose in mice after sucrose loading.
      Further studies showed that PB2 revealed strong inhibitory activity against alpha
      glucosidase with an IC50 value of (0.23 +/- 0.01) MUg mL-1, and this process was
      reversible with a mixed-type inhibitory manner. PB2 quenched the intrinsic
      fluorescence of alpha-glucosidase through a static quenching mechanism and
      changed the micro-environments and conformations of alpha-glucosidase that led to
      an aggregation phenomenon. A further molecular docking study provided more
      information about the interactions of PB2 with the amino acid residues of alpha
      glucosidase. Our results suggest that PB2 is useful for protection against
      hyperglycemia through inhibiting the activity of alpha-glucosidase.

PMID- 30188555
TI  - Effect of polysaccharide FMP-1 from Morchella esculenta on melanogenesis in
      B16F10 cells and zebrafish.
AB  - Polysaccharides from Morchella esculenta are known to exhibit diverse
      bioactivities, while an anti-melanogenesis effect has been barely addressed.
      Herein, the anti-melanogenesis activity of a heteropolysaccharide from M.
      esculenta (FMP-1) was investigated in vitro and in vivo. FMP-1 had no significant
      cytotoxic effect on B16F10 melanoma cells as well as zebrafish larvae, but did
      reduce melanin contents and tyrosinase activities in both of them. Treatment with
      FMP-1 also effectively suppressed the expression of melanogenesis-related
      proteins, including MC1R, MITF, TRP-1 and TRP-2, through decreasing the
      phosphorylation of cyclic adenosine monophosphate response element-binding
      protein (CREB). Moreover, the mitogen-activated protein kinase (MAPK) pathway was
      observed mediating FMP-1's inhibitory effect against melanin production.
      Specifically, FMP-1 treatment markedly inhibited the activation of
      phosphorylation of p38 mitogen-activated protein kinase. These results suggested
      that FMP-1's inhibitory effect against melanogenesis is mediated by the
      inhibition of CREB and p38 signaling pathways, thereby resulting in the
      downstream repression of melanogenesis-related proteins and the subsequent
      melanin production. These data provide insight into FMP-1's potential anti
      melanogenesis effect in food and cosmetic industries.

PMID- 30188556
TI  - Fundamental Concepts of Azole Compounds and Triazole Antifungals: A Beginner's
      Review.
AB  - Azoles are the most widely used drugs in antifungal therapy. They have a wide
      spectrum of activity against pathogenic fungi that are clinically relevant.
      However, they have been associated with adverse reactions and toxicity, both of
      which can be significant in patients. Compared to diazoles, triazoles
      discriminate better between their intended molecular target, the fungal CYP51
      enzyme, and several enzymes of the human CYP450 system. Over the years, this
      superior discrimination has led to the favoring of triazoles over diazoles in the
      treatment of systemic mycoses. Nevertheless, despite their being better able to
      discriminate between the fungal CYP51 and host CYP450 enzymes, they are still
      capable of inducing significant toxicity and adverse reactions in the host,
      especially when taken concomitantly with other therapeutic drugs by patients with
      compromised immune systems. In this writing, we review some of the fundamental
      concepts regarding the chemistry and mechanisms of action of azole compounds, as
      well as the spectrum of activity, pharmacokinetics, and adverse effects of
      triazole antifungals. In addition, we discuss some of the mechanisms that
      pathogenic fungi have developed to overcome the cytotoxic effects of therapeutic
      drugs, with an emphasis on triazoles.

PMID- 30188557
TI  - Effect of Season on 25-OH Vitamin D in Serum of Rhesus Monkeys Housed in Puerto
      Rico.
AB  - OBJECTIVE: Vitamin D blood levels have been shown to be partially dependent upon
      season in temperate climates, however, this same evaluation has not yet been
      reported in fully tropical climates. Herein, we assessed the vitamin D levels in
      the blood of Rhesus monkeys housed at the Puerto Rico Caribbean Primate Research
      Center collected in the island's "summer"(May-October) and "winter" (November
      April) months. MATERIALS AND METHODS: In 2006 through 2014, repeated measurements
      of blood samples were collected from 5 Rhesus monkeys (IACUC-approved) during
      "summer" and "winter" months to assess 25-OH vitamin D, determined via HPLC. UV-B
      and UV-A (KJ/m2/day) were measured using a ground based radiometer for these time
      periods. A paired t-test and a multilevel mixed- effect model approach was
      performed for data analysis. RESULTS: The difference of the mean serum values of
      25-OH vitamin D between seasons showed lower levels during "winter" than "summer"
      months. About 23% of the variance in levels can be attributed to difference
      between the monkeys. The means of UV-B and UV-A, as a proxy for sunlight
      intensity, were greater (over the entire study interval) during the "summer" as
      opposed to "winter" months (p < 0.001). CONCLUSION: Vitamin D levels were
      substantially higher in the "summer" rather than the "winter" months. This
      observation implies that even in fully tropical regions, such as Puerto Rico,
      time of year can have an influence on vitamin D status. While comparable studies
      have not been undertaken in humans, it would not be unreasonable to suggest that
      similar results would be obtained should such a study be done.

PMID- 30188553
TI  - Protein-protein interactions in "cis-AT" polyketide synthases.
AB  - Covering: up to the end of 2018 Polyketides are a valuable source of bioactive
      and clinically important molecules. The biosynthesis of these chemically complex
      molecules has led to the discovery of equally complex polyketide synthase (PKS)
      pathways. Crystallography has yielded snapshots of individual catalytic domains,
      di-domains, and multi-domains from a variety of PKS megasynthases, and cryo-EM
      studies have provided initial views of a PKS module in a series of defined
      biochemical states. Here, we review the structural and biochemical results that
      shed light on the protein-protein interactions critical to catalysis by PKS
      systems with an embedded acyltransferase. Interactions include those that occur
      both within and between PKS modules, as well as with accessory enzymes.

PMID- 30188558
TI  - Knowledge and Perceptions of E-cigarettes and the Motivations for their Use:
      Talking to Smokers (E-cigarettes and/or Conventional Cigarettes) and Non-smokers
      in Puerto Rico.
AB  - OBJECTIVE: The awareness and use of e-cigarettes have been increasing in recent
      years. The World Health Organization recently reported that regulations are
      needed to impede the promotion of e-cigarettes to young people, prohibit unproven
      health claims about them (including those regarding smoking-cessation efficacy),
      minimize potential health risks to e-cigarette users and non-users, and protect
      existing tobacco controls. The study described herein explored e-cigarette
      knowledge, perceptions, and usage motivations among a group of adults in Puerto
      Rico. METHODS: This research study used a validated questionnaire with closed
      ended questions to gather data. Non-inferential and inferential statistics were
      used to characterize smokers (of e-cigarettes, of conventional cigarettes, and of
      both) and non-smokers. RESULTS: A total of 415 respondents took part; they were
      evenly distributed by gender, age, and socioeconomic status; all were residents
      of Puerto Rico at the time of the survey. The overall awareness of e-cigarettes
      was high, but knowledge of nicotine content and regulations was limited. Asked
      whether e-cigarettes contain nicotine (they do not), approximately two thirds
      stated either that they do or that they didn't know; asked whether e-cigarettes
      are regulated as a tobacco product (they are in Puerto Rico), 84% stated either
      that they are not or that they didn't know. Common perceptions of e-cigarettes
      are that they are harmful to health and that they are no less harmful than
      cigarettes are. However, a significant portion of the respondents perceived e
      cigarettes to be less addictive than conventional cigarettes are. Overall, the
      respondents were divided on the efficacy of e-cigarettes for smoking cessation.
      Nonetheless, the most common motivation for their use, according to both current
      users and potential future users, is to aid in smoking cessation or reduction.
      CONCLUSION: The majority of individuals surveyed were aware of e-cigarettes but
      had limited knowledge of their contents or regulation. As an aid in smoking
      cessation was the most commonly mentioned motivation for e-cigarette use.

PMID- 30188559
TI  - In Vitro Blood-Brain Barrier Modeling adapted for Peripheral Blood Mononuclear
      Cell Transmigration from HIV-Positive Patients for Clinical Research on
      Therapeutic Drug Intervention.
AB  - OBJECTIVE: HIV-associated cognitive impairment (HACI) continues to persist for
      HIV-seropositive individuals who are on antiretroviral therapy (ART). HACI
      develops in part when HIV-infected monocytes (MOs) transmigrate through the blood
      brain barrier (BBB) and secrete pro-inflammatory cytokines and chemokines, which
      leads to neuronal damage. In vitro BBB models are important tools that can
      elucidate mechanisms of MO transmigration. Previously described in vitro BBB
      models relied on pathology specimens, resulting in potentially variable and
      inconsistent results. This project reports on a reliable and consistent
      alternative in vitro BBB model that has the potential to be used in clinical
      research intervention studies analyzing the effects of ART on the BBB and on MO
      transmigration. METHODS: A bilayer BBB model was established with commercially
      available astrocytes and endothelial cells on a 3MUm PET membrane insert to allow
      the contact of astrocytic foot processes with endothelial cells. Inserts were
      cultured in growth medium for 7 days before exposure to HIV- or HIV+ peripheral
      blood mononuclear cells (PBMCs). PBMCs were allowed to transmigrate across the
      BBB for 24 hours. RESULTS: Confluency and integrity measurements by trans
      endothelial electrical resistance (TEER) (136.7 +/- 18.3Omega/cm2) and
      permeability (5.64 +/- 2.20%) verified the integrity of the in vitro BBB model.
      Transmigrated MOs and non-MOs were collected and counted (6.0x104 MOs; 1.1x105
      non-MOs). Markers indicative of glial fibrillary acidic protein (GFAP), von
      Willebrand factor (vWF), and p-glycoprotein (Pgp) were revealed in
      immunofluorescence staining (IF), indicating BBB phenotype and functionality.
      CONCLUSION: Potential applications for this model include assessing the HIV DNA
      copy numbers of transmigrated cells (pre- and post-targeted ART) and
      understanding the role of oxidative stress related to HIV DNA and HACI.

PMID- 30188560
TI  - The Factors Significantly affecting the Quality of Life of Patients Who undergo
      Radical Cystectomy due to Bladder Cancer.
AB  - OBJECTIVE: Bladder cancer is, in Poland, the fourth most common malignancy in men
      and the eighth most common in women. Radical cystectomy often seems to be the
      only method of treatment. This mutilating procedure may affect the quality of
      life of the patient. The aim of our study was to analyze the impact of factors
      influencing quality of life in patients after a cystectomy. METHODS: From January
      to August 2015, 50 consecutive patients treated in the Department of Urology of
      the Wroclaw Medical University in Wroclaw were enrolled into the study. Sixty
      three percent of the respondents were men. Fifty-two percent of the respondents
      lived in urban areas. Patients ranged in age from under 25 to over 51 years.
      Clinical and demographic data were collected. Quality of life was evaluated with
      the SF-36 health survey questionnaire. For statistical analysis, Student's t
      test, the Mann-Whitney U test and Spearman's rank correlation coefficient were
      used. Statistical analysis was carried out with IBM SPSS Statistics for Windows
      Version 21.0. RESULTS: A decrease in quality of life was observed in both
      genders. The impact of place of residence on the occurrence of pain, health
      perception, vitality, and levels of physical and mental activity was found to be
      significant (p<0.05). Pain intensity, health perception, vitality, and levels of
      physical and mental activity were higher in patients living in urban areas.
      CONCLUSION: Patients with bladder cancer who underwent a radical cystectomy were
      more likely to have a reduced quality of life if they lived in a village or small
      town than if they lived in an urban area.

PMID- 30188561
TI  - Body Mass Index and Surgical Outcome in a Puerto Rican Population.
AB  - OBJECTIVE: To determine the impact of body mass index (BMI) on postoperative
      morbidity and 30-day mortality in the population served by the University of
      Puerto Rico (UPR)-affiliated hospitals. METHODS: We reviewed the surgical data
      entered into the UPR General Surgery Department database from January 1, 2014,
      through June 30, 2016. This database collects patient and procedural information
      from the UPR-affiliated hospitals. We compared the postoperative morbidity and 30
      day mortality rates of 5 different BMI groups: underweight (<18.5 kg/m2), normal
      weight (18.5-24.9 kg/m2), overweight (25.0-29.9 kg/m2), obese, classes I and II
      (30-39.9 kg/m2), and morbidly obese (>=40 kg/m2). Multivariable regression
      analyses, adjusted for age, gender, and surgery type, were used to evaluate the
      risks for each BMI category. RESULTS: Information on 9,856 patients was reviewed.
      The mean age of the sample population was 52 (+/-20) years; 57% were women and
      43% were men. The postoperative morbidity and 30-day mortality rates of the
      underweight group were significantly higher than those of the normal-weight group
      (6.1% vs. 3.1% and 2.1% vs. 0.5%, respectively; p<0.001). The morbidly obese also
      had significantly higher (p<0.001) postoperative morbidity (5.3% vs. 2.1%) and 30
      day mortality rates (2.7% vs. 0.5%) compared to normal-weight patients. The odds
      of 30-day mortality were significantly higher for the underweight (odds ratio
      [OR], 5.64; 95% confidence interval [CI], 2.47-12.92) and morbidly obese patients
      (OR, 7.23; 95% CI, 3.01-17.39). The overweight patients had no increased risk,
      and the obese patients had a slight increase in morbidity (OR, 1.54; 95% CI, 1.08
      2.21) but no significant increase in 30-day mortality (p>0.05). CONCLUSION:
      Patients at the extremes of the BMI have more postoperative complications and
      higher 30-day mortality rates than do patients with mid-range scores.

PMID- 30188562
TI  - Minimally Invasive Complete Mouth Reconstruction using Full-Contour Ceramic
      Veneers: A Clinical Report.
AB  - This case report illustrates a full-mouth rehabilitation for a patient that
      presented with severe non-carious tooth surface loss. The patient was restored
      following a minimally invasive tooth preparation, with 28 full-contour veneers.
      The patient was evaluated at baseline and at 2, 9, and 13 months following
      cementation to assess the integrity of the restorations, the proximal and
      occlusal contacts, pulp vitality, and tooth mobility. After 13 months, no
      postoperative sensitivity was reported. In addition, no secondary caries, loss of
      tooth vitality, or chipping or fractures of the veneers were detected. The
      clinical outcome of using a minimally invasive adhesive technique was an
      esthetic, mechanical, and biological success.

PMID- 30188563
TI  - Chordoid Glioma with Psychosis: Case Report.
AB  - OBJECTIVE: A rare, low-grade tumor found in the hypothalamus and anterior third
      ventricle, a chordoid glioma presents a challenge to neurosurgeons: Its
      successful resection is complicated by its inconvenient location. CASE
      DESCRIPTION: A 42-year-old male patient presented with a 1-year history of major
      depressive disorder, with psychotic features associated with generalized tonic
      clonic seizures. Brain magnetic resonance imaging (MRI) with contrast revealed a
      suprasellar mass extending into the third ventricle To resect the lesion, an
      interhemispheric transcallosal transventricular subfornical approach was used.
      Pathology revealed a chordoid glioma. The patient had a complicated post
      operative period that included the development of neurogenic diabetes insipidus,
      followed by intractable hyponatremia and death (caused by malignant brain edema).
      CONCLUSION: A chordoid glioma is a rare neoplasm that, in 2000, was incorporated
      into the World Health Organization (WHO) classification of central nervous system
      tumors. Due to its rarity, it is seldom considered in the differential diagnosis
      of suprasellar masses. Moreover, its unusual presentation and difficult location
      present a challenge for surgical and medical management.

PMID- 30188564
TI  - Anesthesia's Role in Cancer Recurrence.

PMID- 30188565
TI  - Short-course versus long-course therapy of the same antibiotic for community
      acquired pneumonia in adolescent and adult outpatients.
AB  - BACKGROUND: Community-acquired pneumonia (CAP) is a lung infection that can be
      acquired during day-to-day activities in the community (not while receiving care
      in a hospital). Community-acquired pneumonia poses a significant public health
      burden in terms of mortality, morbidity, and costs. Shorter antibiotic courses
      for CAP may limit treatment costs and adverse effects, but the optimal duration
      of antibiotic treatment is uncertain. OBJECTIVES: To evaluate the efficacy and
      safety of short-course versus longer-course treatment with the same antibiotic at
      the same daily dosage for CAP in non-hospitalised adolescents and adults
      (outpatients). We planned to investigate non-inferiority of short-course versus
      longer-term course treatment for efficacy outcomes, and superiority of short
      course treatment for safety outcomes. SEARCH METHODS: We searched CENTRAL, which
      contains the Cochrane Acute Respiratory Infections Group Specialised Register,
      MEDLINE, Embase, five other databases, and three trials registers on 28 September
      2017 together with conference proceedings, reference checking, and contact with
      experts and pharmaceutical companies. SELECTION CRITERIA: Randomised controlled
      trials (RCTs) comparing short- and long-courses of the same antibiotic for CAP in
      adolescent and adult outpatients. DATA COLLECTION AND ANALYSIS: We planned to use
      standard Cochrane methods. MAIN RESULTS: Our searches identified 5260 records. We
      did not identify any RCTs that compared short- and longer-courses of the same
      antibiotic for the treatment of adolescents and adult outpatients with CAP.We
      excluded two RCTs that compared short courses (five compared to seven days) of
      the same antibiotic at the same daily dose because they evaluated antibiotics
      (gemifloxacin and telithromycin) not commonly used in practice for the treatment
      of CAP. In particular, gemifloxacin is no longer approved for the treatment of
      mild-to-moderate CAP due to its questionable risk-benefit balance, and reported
      adverse effects. Moreover, the safety profile of telithromycin is also cause for
      concern.We found one ongoing study that we will assess for inclusion in future
      updates of the review. AUTHORS' CONCLUSIONS: We found no eligible RCTs that
      studied a short-course of antibiotic compared to a longer-course (with the same
      antibiotic at the same daily dosage) for CAP in adolescent and adult outpatients.
      The effects of antibiotic therapy duration for CAP in adolescent and adult
      outpatients remains unclear.

PMID- 30188566
TI  - Impact of public release of performance data on the behaviour of healthcare
      consumers and providers.
AB  - BACKGROUND: It is becoming increasingly common to publish information about the
      quality and performance of healthcare organisations and individual professionals.
      However, we do not know how this information is used, or the extent to which such
      reporting leads to quality improvement by changing the behaviour of healthcare
      consumers, providers, and purchasers. OBJECTIVES: To estimate the effects of
      public release of performance data, from any source, on changing the healthcare
      utilisation behaviour of healthcare consumers, providers (professionals and
      organisations), and purchasers of care. In addition, we sought to estimate the
      effects on healthcare provider performance, patient outcomes, and staff morale.
      SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and two trials registers on
      26 June 2017. We checked reference lists of all included studies to identify
      additional studies. SELECTION CRITERIA: We searched for randomised or non
      randomised trials, interrupted time series, and controlled before-after studies
      of the effects of publicly releasing data regarding any aspect of the performance
      of healthcare organisations or professionals. Each study had to report at least
      one main outcome related to selecting or changing care. DATA COLLECTION AND
      ANALYSIS: Two review authors independently screened studies for eligibility and
      extracted data. For each study, we extracted data about the target groups
      (healthcare consumers, healthcare providers, and healthcare purchasers),
      performance data, main outcomes (choice of healthcare provider, and improvement
      by means of changes in care), and other outcomes (awareness, attitude, knowledge
      of performance data, and costs). Given the substantial degree of clinical and
      methodological heterogeneity between the studies, we presented the findings for
      each policy in a structured format, but did not undertake a meta-analysis. MAIN
      RESULTS: We included 12 studies that analysed data from more than 7570 providers
      (e.g. professionals and organisations), and a further 3,333,386 clinical
      encounters (e.g. patient referrals, prescriptions). We included four cluster
      randomised trials, one cluster-non-randomised trial, six interrupted time series
      studies, and one controlled before-after study. Eight studies were undertaken in
      the USA, and one each in Canada, Korea, China, and The Netherlands. Four studies
      examined the effect of public release of performance data on consumer healthcare
      choices, and four on improving quality.There was low-certainty evidence that
      public release of performance data may make little or no difference to long-term
      healthcare utilisation by healthcare consumers (3 studies; 18,294 insurance plan
      beneficiaries), or providers (4 studies; 3,000,000 births, and 67 healthcare
      providers), or to provider performance (1 study; 82 providers). However, there
      was also low-certainty evidence to suggest that public release of performance
      data may slightly improve some patient outcomes (5 studies, 315,092
      hospitalisations, and 7502 providers). There was low-certainty evidence from a
      single study to suggest that public release of performance data may have
      differential effects on disadvantaged populations. There was no evidence about
      effects on healthcare utilisation decisions by purchasers, or adverse effects.
      AUTHORS' CONCLUSIONS: The existing evidence base is inadequate to directly inform
      policy and practice. Further studies should consider whether public release of
      performance data can improve patient outcomes, as well as healthcare processes.

PMID- 30188567
TI  - Identification and characterization of capa and pyrokinin genes in the brown
      marmorated stink bug, Halyomorpha halys (Hemiptera): Gene structure,
      immunocytochemistry, and differential expression.
AB  - CAPA and pyrokinin (PK) neuropeptides are produced from two different genes, capa
      and pyrokinin, respectively. In this study, we identified and characterized the
      capa and pyrokinin genes from the brown marmorated stink bug, Halyomorpha halys
      (Hemiptera). The capa gene encodes two CAPA-PVK (periviscerokinin) peptides
      (DAGLFPFPRVamide and EQLIPFPRVamide) and one CAPA-DH (diapause hormone;
      NGASGNGGLWFGPRLamide). The pyrokinin gene encodes three PK2 peptides
      (QLVSFRPRLamide, SPPFAPRLamide, and FYAPFSPRLamide). The whole-mounting
      immunocytochemistry revealed the neurons contained PRXamide-like peptides
      throughout the cerebral ganglia (CRG), gnathal ganglia (GNG), thoracic ganglia
      (TG), and abdominal ganglia (AG). A pair of neurosecretory cells in the CRG and
      three cell clusters in the GNG were found with the axonal projections extended
      through the lateral side. A pair of immunostained cells were found in the TG,
      while three pairs of cells were present in the fused AG. Different expression
      patterns of capa and pyrokinin genes were observed in the CRG-GNG, TG, and AG.
      The capa gene was highly expressed in the AG tissue, whereas the pyrokinin gene
      was strongly expressed in the CRG-GNG. Interestingly, different developmental
      stages showed similar expressions of both genes, with the highest from the first
      nymph, gradually decreasing to the female adult. Comparison of peptide sequences
      encoded from pyrokinin genes showed the PK1 peptide is lost in Heteroptera
      suborders including H. halys, but retained in other suborders. The missing PK1
      from the pyrokinin gene might be compensated by CAPA-DH (=PK1-like) produced by
      the capa gene.

PMID- 30188568
TI  - A new clinical variant of acquired reactive perforating dermatosis-like bullous
      pemphigoid.

PMID- 30188569
TI  - Labeled gangliosides: their synthesis and use in biological studies.
AB  - The unveiling of ganglioside metabolism and biological function in the last
      decades depended on the extensive study of inherited human disease, studies with
      cultured cells, and specifically designed mouse models. Nonetheless, only few of
      the accomplishments made so far would have been possible without the use of
      labeled gangliosides, such as their radiolabeled and/or fluorescent analogs, as
      well as other modified gangliosides bearing cross-linking, affinity, or
      paramagnetic groups. Over the years, chemists and biochemists have made
      tremendous progress toward developing labeled gangliosides for their application
      in biological systems. These labeled ganglioside probes of the ganglio series
      have been successfully incorporated in cultured vertebrate cells and in
      artificial model membranes. In this Review, I provide an overview over the
      different methods, mostly semisynthetic procedures, to obtain these labeled
      ganglioside probes that have been used to elucidate the molecular basis of
      ganglioside-related biology as well as the physicochemical properties of
      gangliosides.

PMID- 30188570
TI  - Local interventions for actinic keratosis in organ transplant recipients: a
      systematic review.
AB  - BACKGROUND: Actinic keratosis (AK) in organ transplant recipients (OTRs) has a
      high risk of progressing to invasive squamous cell carcinoma of the skin. Thus,
      early and consequent treatment of AKs is warranted in OTRs. OBJECTIVES: To
      summarize the current evidence for nonsystemic treatments of AKs in OTRs.
      METHODS: We performed a systematic literature search in MEDLINE, Embase and the
      Cochrane Central Register of Controlled Trials (CENTRAL) and hand-searched
      pertinent trial registers up to 22 August 2018. Randomized controlled trials
      (RCTs) evaluating nonsystemic interventions for AKs in OTRs were included. The
      risk of bias was estimated using the Cochrane Risk of Bias Tool. RESULTS: Of 663
      records initially identified, eight RCTs with 242 OTRs were included in a
      qualitative synthesis. Most studies evaluated methyl aminolaevulinate
      photodynamic therapy (MAL-PDT), followed by ablative fractional laser (AFXL) and
      diclofenac sodium 3% in hyaluronic acid, imiquimod 5% cream and 5-fluorouracil 5%
      cream (5-FU). MAL-PDT showed the highest rates of participant complete clearance
      (40-76.4%), followed by imiquimod (27.5-62.1%), diclofenac (41%) and 5-FU (11%).
      Similar results were observed for lesion-specific clearance rates. Treatment with
      AFXL alone revealed low lesion clearance (5-31%). Local skin reactions were most
      intense in participants treated with a combination of AFXL and daylight MAL-PDT.
      There were no therapy-related transplant rejections or worsening of graft
      function in any trial. The overall risk of bias was high. CONCLUSIONS: Limited
      evidence is available for the treatment of AKs in OTRs. MAL-PDT is currently the
      best-studied intervention. Lesion-specific regimens may not be sufficient to
      achieve disease control. Field-directed regimens are preferable in this high-risk
      population.

PMID- 30188573
TI  - NGWA News.

PMID- 30188571
TI  - Benefit-risk profile of tofacitinib in patients with moderate-to-severe chronic
      plaque psoriasis: pooled analysis across six clinical trials.
AB  - BACKGROUND: Although existing psoriasis treatments are effective and well
      tolerated in many patients, there is still a need for new effective targeted
      treatment options. Tofacitinib is an oral Janus kinase inhibitor that has been
      investigated in patients with moderate-to-severe chronic plaque psoriasis.
      OBJECTIVES: To consider the benefits and risks of tofacitinib in patients with
      moderate-to-severe psoriasis. METHODS: Data were pooled from one phase II, four
      phase III and one long-term extension study comprising 5204 patient-years of
      tofacitinib treatment. Efficacy end points included patients achieving
      Physician's Global Assessments of 'clear' or 'almost clear', >= 75% and >= 90%
      reduction in Psoriasis Area and Severity Index (coprimary end points) and
      improvements in Dermatology Life Quality Index score, Hospital Anxiety and
      Depression Scale depression score and Itch Severity Item score, at weeks 16 and
      52. Safety data were summarized for 3 years of tofacitinib exposure. RESULTS:
      Tofacitinib 5 and 10 mg twice daily (BID) showed superiority over placebo for all
      efficacy end points at week 16, with response maintained for 52 weeks of
      continued treatment. Tofacitinib improved patients' quality of life and was well
      tolerated. Rates of safety events of interest (except herpes zoster) were similar
      to those in the published literature and healthcare databases for other systemic
      psoriasis therapies. Tofacitinib 10 mg BID demonstrated greater efficacy than 5
      mg BID. CONCLUSIONS: Tofacitinib has a benefit-risk profile in moderate-to-severe
      psoriasis consistent with that of other systemic treatments.

PMID- 30188572
TI  - GENIPSO: a French prospective study assessing instantaneous prevalence, clinical
      features and impact on quality of life of genital psoriasis among patients
      consulting for psoriasis.
AB  - BACKGROUND: Genital psoriasis is often under-recognized. OBJECTIVES: To assess
      the instantaneous prevalence of genital psoriasis and describe its clinical
      features, association with a particular subtype of psoriasis and its impact on
      general and sexual quality of life (QoL). METHODS: GENIPSO is a prospective study
      conducted by private and hospital-based dermatologists. This study featured the
      consecutive inclusion of patients consulting for extragenital psoriasis. The
      clinical features of psoriasis and genital psoriasis were recorded and QoL and
      sexual health questionnaires were distributed to patients. RESULTS: Overall, 335
      of 776 patients (43.2%) included in the study had genital involvement. All were
      aware that they had genital lesions but only 135 patients (40%) declared that
      they had been previously examined. Genital lesions were associated with male sex,
      severity of psoriasis, age of onset > 20 years, inverse psoriasis and involvement
      of scalp, nail and external auditory canal, but were not associated with obesity,
      psoriatic arthritis and active sex life. Itching was the main symptom. Genital
      psoriasis was associated with impairment of QoL and sexual health according to
      the Dermatology Life Quality Index and the Female Sexual Function Index.
      CONCLUSIONS: Genital psoriasis has a high prevalence in patients consulting for
      extragenital psoriasis, which affects QoL, and should be taken into account by
      dermatologists in order to optimize global care.

PMID- 30188574
TI  - Parasites and allergy: Observations from Brazil.
AB  - Brazil is a middle-income country undergoing the epidemiological transition.
      Effects of changes in daily life habits and access to clean water, sanitation and
      urban services on a growing urban population have contributed to a double burden
      of both infectious and noncommunicable chronic diseases. Studies have indicated
      that parasite infections may modulate the human immune system and influence the
      development of allergic conditions such as asthma. However, there is no consensus
      in the published literature on the effects of parasitic infections on allergy,
      perhaps as a consequence of factors determining the epidemiology of these
      infections that vary between populations such as age of first infection, duration
      and chronicity of infections, parasite burden and species, and host genetic
      susceptibility. In this review, we discuss the observations from Brazil
      concerning the relationship between parasite infections and allergy.

PMID- 30188575
TI  - Missed Druggable Cancer Hallmark: Cancer-Stroma Symbiotic Crosstalk as Paradigm
      and Hypothesis for Cancer Therapy.
AB  - During tumor evolution, cancer cells use the tumor-stroma crosstalk to reorganize
      the microenvironment for maximum robustness of the tumor. The success of immune
      checkpoint therapy foretells a new cancer therapy paradigm: an effective cancer
      treatment should not aim to influence the individual components of super complex
      intracellular interactomes (molecular targeting), but try to disrupt the
      intercellular interactions between cancer and stromal cells, thus breaking the
      tumor as a whole. Arguments are provided in favor of a hypothesis that such
      interactions include formation of synapse-like structures (interfaces) where the
      interacting cells are located at a distance of ~10-15 nm. Within these
      interfaces, molecules initiating and strengthening the interaction are organized,
      and allow optimum cross-signaling; a very confined intercellular space
      facilitates the concentration of secreted cytokines, enhancing the paracrine
      cross-communication. These features of tumors form a druggable cancer hallmark
      the tumor-stroma symbiotic crosstalk-which represents a new target for efficient
      cancer drug discovery.

PMID- 30188576
TI  - Addition of oral minipulse dexamethasone to narrowband ultraviolet B phototherapy
      and topical steroids helps arrest disease activity in patients with vitiligo.

PMID- 30188577
TI  - Dynamics of partially obstructed breakup of bubbles in microfluidic Y-junctions.
AB  - For revealing the dynamics of partially obstructed breakup of bubbles in
      microfluidic Y-junctions, the combination of dimensionless power-law and
      geometric model was applied to study the effects of capillary number, bubble
      length, and channel angle on the bubble rupture process. In the squeezing
      process, the gas-liquid interface curve follows the parabolic model. For the
      evolution of the bubble neck during breakup, the increase of the bubble length,
      the channel angle, and the capillary number leads to the decrease of the focus
      distance alpha. The chord m increases with the increase of the capillary number
      and the decrease of the bubble length, and it would reach the maximum value when
      the channel angle is 90 degrees . In the fast pinch-off stage during bubble
      breakup, the bubble's neck curve no longer conforms to the parabolic model so the
      focus and chord no longer exist. For the evolution of the bubble head during
      breakup, the value of gamma approaches 1 with the increase of the capillary
      number and the bubble length, and with the close of the channel angle to 90
      degrees . It is found that the quadrilateral model can be applied for the
      partially obstructed rupture of bubbles in the symmetrical microfluidic Y
      junction.

PMID- 30188578
TI  - Linear epitopes in Onchocerca volvulus vaccine candidate proteins and excretory
      secretory proteins.
AB  - In our previous study, a proteome-wide screen was conducted to identify linear
      epitopes in this parasite's proteome, resulting in the discovery of three
      immunodominant motifs. Here, we investigated whether such antigenic peptides were
      found in proteins that were already known as vaccine candidates and
      excretome/secretome proteins for Onchocerca volvulus This approach led to the
      identification of 71 immunoreactive stretches in 46 proteins. A deep-dive into
      the immunoreactivity profiles of eight vaccine candidates that were chosen as
      most promising candidates for further development (Ov-CPI-2, Ov-ALT-1, Ov-RAL-2,
      Ov-ASP-1, Ov-103, Ov-RBP-1, Ov-CHI-1, and Ov-B20), resulted in the identification
      of a poly-glutamine stretch in Ov-RAL-2 that has properties for use as a
      serodiagnostic marker for O. volvulus infection. A peptide ELISA was developed,
      and the performance of this assay was evaluated. Based on this assessment, it was
      found that this assay has a sensitivity of 75.0% [95% CI: 64.9%-83.5%] and a
      specificity of 98.5% [95% CI: 94.6%-99.8%]. Furthermore, 8.7% reactivity in Asian
      parasite-infected individuals (8 out of 92) was observed. Besides this
      identification of a linear epitope marker, the information on the presence of
      linear epitopes in vaccine candidate proteins might be useful in the study of
      vaccines for river blindness.

PMID- 30188579
TI  - Intraoral granulocytic sarcoma as a manifestation of myelofibrosis: A case report
      and review of the literature.
AB  - Granulocytic sarcoma (GS) is an extramedullary tumor associated with
      myelodysplastic syndromes or myeloproliferative diseases. Intraoral
      manifestations are considered uncommon, with a reasonable number of cases, and
      are mostly related to leukemia. The association of oral GS and myelofibrosis is
      very rare and only three cases have been published. In this paper, we report the
      fourth case of oral lesion in a patient with a diagnosis of myelofibrosis. The
      aim of this study was to present a review of the literature, discussing the
      current and previous cases of oral GS associated with myelofibrosis or other
      hematological disorders and the importance of accurate diagnosis through
      clinical, microscopic, and immunohistochemical features.

PMID- 30188581
TI  - Placental volume at 11 to 14 gestational weeks in pregnancies complicated with
      fetal growth restriction and preeclampsia.
AB  - OBJECTIVE: The study aims to evaluate the predictive value of first trimester
      placental volume in pregnancies destined to develop fetal growth restriction
      (FGR) and preeclampsia (PE). METHODS: Prospective observational study including
      placentas from 34 FGR, 12 PE, 15 GH (gestational hypertension) pregnancies, and
      265 controls. Placental volume (PV) was obtained using VOCAL technique, and a z
      score was calculated (z-PV). The association of PV with other first trimester
      variables and maternal characteristics was assessed with Spearman's correlation.
      RESULTS: PV increased exponentially with crown-rump length (CRL) and was
      unrelated to maternal factors (weight, age, parity, and smoking status) as well
      as first trimester uterine artery Doppler, free beta-hCG, nuchal translucency, or
      fetal heart rate. However, PV was positively associated with maternal height,
      CRL, PAPP-A, and birth weight. z-PV was a strong predictor for FGR with abnormal
      fetal Dopplers (AUC = 0.9472, P < 0.001). z-PV provided moderate prediction of
      FGR with normal fetal Dopplers (AUC = 0.8396, P < 0.001), PE (AUC = 0.8312, P <
      0.001), and GH (AUC = 0.7640, P < 0.001). The addition of maternal weight, PAPP
      A, beta-hCG, and uterine artery Doppler improved our models. CONCLUSION: At 11 to
      14 weeks, PV is an independent predictor of pregnancy complications related to
      placental insufficiency, and the predictive ability is greater for FGR
      pregnancies with abnormal fetal Dopplers.

PMID- 30188580
TI  - Prediction of immunoglobulin M reduction via therapeutic dose of simple plasma
      exchange and double filtration plasmapheresis using membrane separation in
      patients with hyperviscosity syndrome caused by Waldenstrom macroglobulinemia.
AB  - BACKGROUND: Plasma exchange (PE) and double filtration plasmapheresis (DFPP) are
      known as effective treatment options for hyperviscosity syndrome (HVS) caused by
      Waldenstrom macroglobulinemia. Nonetheless, few data are available for the
      relation between the prescribed dose of apheresis and the reduction rate of
      target molecule immunoglobulin M (IgM), especially in the modality using membrane
      separation. OBJECTIVES: This study was conducted to establish a model to predict
      the IgM reduction rate by the dose of simple PE and DFPP using membrane
      separation in patients with HVS and to compare the consumption of albumin between
      PE and DFPP. METHODS: We retrospectively analyzed data of total 17 sessions of PE
      and DFPP with various therapeutic doses performed for five patients at our
      institution. We used linear regression analysis to examine the relation between
      the ratio of processed plasma volume to estimated circulating plasma volume (X)
      and the reduction rate of IgM (Y). RESULTS: Regression analysis revealed that Y
      is expressed by X as the following equation: Y = 0.35X + 0.095. The total usage
      of albumin for replacement fluid was lower in DFPP than in PE (21.5 g vs 150 g
      per session), although the treatment efficacies of both modalities are similar.
      CONCLUSION: The dose of PE and DFPP using membrane separation can predict IgM
      reduction rate in the HVS patients. Predicted IgM reduction rates based on our
      model are lower than those calculated using a known theoretical model. In terms
      of the amount of use of albumin, DFPP is preferred to PE.

PMID- 30188582
TI  - Primary cicatricial alopecia in a single-race Asian population: A 10-year
      nationwide population-based study in South Korea.
AB  - Primary cicatricial alopecia (PCA) is a dermatological challenge. Because no
      large-scale epidemiological study regarding PCA is available yet, we investigated
      the National Health Insurance Service-National Sample Cohort for patients
      diagnosed with PCA. The annual and overall rates of incidence and prevalence of
      PCA during the study period (2004-2013) were estimated. Distribution of PCA
      subtypes, disease co-occurrence rates and frequently prescribed medications were
      also evaluated. The overall incidence was 6.10 (95% confidence interval [CI],
      5.62-6.60) per 100 000 person-years. The incidence rate was stable over time
      (risk ratio [RR] = 1.012, P = 0.201) and lower in female patients (RR = 0.718, P
      < 0.001). The overall prevalence was 20.93 (95% CI, 17.97-23.86) per 100 000
      persons. The average duration of PCA was calculated as 3.23 years. Approximately
      70% of the patients were below the age of 45 years. Folliculitis decalvans and
      dissecting cellulitis were the most common subtypes of PCA. Logistic regression
      analysis showed that PCA was significantly associated with thyroid disorders
      (adjusted odds ratio = 1.64, P < 0.001). Clobetasol was the most frequently
      prescribed topical agent. Corticosteroids were the most common oral agents used,
      followed by tetracycline antibiotics. Our study is the first large-scale study
      reporting the epidemiology of PCA. We found a preponderance of males and
      neutrophil-associated subtypes of PCA, and PCA was related to thyroid disorders.

PMID- 30188583
TI  - Evaluation of phytomedicinal potential of perillyl alcohol in an in vitro
      Parkinson's Disease model.
AB  - Preclinical Research & Development Parkinson's disease (PD) is the second most
      common neurodegenerative disorder that affects approximately 10 million people
      worldwide. The risk of developing PD and similar neurodegenerative disorders
      increases with age and an estimated 4% people are diagnosed with the disease
      before reaching the age of 50. Oxidative stress, cytotoxicity, and mitochondrial
      dysfunction are common features exhibited in the development of PD. The 6
      hyroxydopamine (6-OHDA) model of PD is one of the most well characterized and
      studied models of the disease. 6-OHDA, a neurotoxin, can induce most
      characteristic features of the disease, including mitochondrial dysfunction in
      vivo and in-vitro. SH-SY5Y is a neuroblastoma cell line of human origin that has
      been used for dose response studies on PD in the past. Based on previous data, we
      have used SH-SY5Y cells as an in-vitro model of PD to analyse the phytomedicinal
      potential of perillyl alcohol (PA), a monoterpenoid obtained from essential oils
      of various plants such as sage, peppermint and lavender. We have found that
      pretreatment with PA (10 MUM and 20 MUM) mitigated 6-OHDA (150 MUM) induced
      cytotoxicity in a dose-dependent manner. We observed marked restoration of cell
      viability and mitochondrial membrane potential (MMP) as well as reduced reactive
      oxygen species generation, Cytochrome c immunofluorescence and DNA fragmentation
      after treatment with PA. On the basis of on our data, we have come to the
      conclusion that PA demonstrates sufficient neuroprotective activity to provide
      new avenues in therapy of PD and its apparent target being restoration of MMP can
      lead to better understanding of the disease.

PMID- 30188584
TI  - Cyclodextrin complexes: Perspective from drug delivery and formulation.
AB  - Cyclodextrins (CDs) have been widely investigated as a unique pharmaceutical
      excipient for past few decades and is still explored for new applications. They
      are highly versatile oligosaccharides which possess multifunctional
      characteristics, and are mainly used to improve the physicochemical stability,
      solubility, dissolution rate, and bioavailability of drugs. Stability constant,
      factors affecting complexation, techniques to enhance complexation efficiency,
      the preparation methods for molecular inclusion complexes and release of guest
      molecules are discussed in brief. In addition, different CD derivatives and their
      pharmacokinetics are elaborated. Further, the significance of CD complex in
      aqueous solubility, dissolution and bioavailability, stability, and taste masking
      is explained. The recent advancement of CDs in developing various drug delivery
      systems is enlightened. Indeed, the potential of CDs by means of inclusion
      complex formation have widen the applicability of these materials in various drug
      delivery systems including ocular, osmotic, mucoadhesive, transdermal, nasal, and
      targeted delivery systems. Feasibility studies have been performed on the benefit
      of these cyclic oligomers as nanocarriers, a strategy that can modify the drugs
      with improved physicochemical properties. Studies also demonstrated the
      feasibility of CDs to self-assemble in the form of stable nanoaggregates, which
      may extend the scope of CDs in drug delivery to the continually expanding list of
      new drug entities.

PMID- 30188585
TI  - Anorectic efficacy and safety of the diethylpropion-topiramate combination in
      rats.
AB  - Preclinical Research & Development Current drugs for obesity treatment have
      limited efficacy and considerable adverse effects. Combination of drugs with
      complementary mechanisms of action at lower doses may produce a greater efficacy
      with a better safety profile. This study was designed to assess the anorectic
      effect and safety of a diethylpropion + topiramate mixture in rats. The anorectic
      effect of drugs was measured using a sweetened milk consumption model, and the
      corresponding interaction was determined by isobolographic analysis, interaction
      index and confidence intervals. Additionally, blood pressure was measured using a
      sphygmomanometer in the rat tail. Diethylpropion and topiramate alone or in
      combination increased the anorectic effect in a dose-dependent fashion in either
      nondeprived or 12 hr food-deprived rats. All theoretical ED30 values of
      diethylpropion + topiramate combinations at 1:1, 1:3, and 3:1 dose ratios were
      significantly higher than experimental ED30 values. In addition, interaction
      indices and confidence intervals confirmed the potentiation between both drugs.
      Theoretical ED30 of diethylpropion + topiramate combination did not affect the
      blood pressure. Data suggests that low doses of the diethylpropion + topiramate
      combination can potentiate the anorectic effect of individual drugs with a better
      safety profile, which deserves further investigation in clinical trials.

PMID- 30188586
TI  - Synergistic interaction between docosahexaenoic acid and diclofenac on
      inflammation, nociception, and gastric security models in rats.
AB  - Preclinical Research & Development The addition of polyunsaturated fatty acids to
      nonsteroidal anti-inflammatory drugs can increase their antinociceptive activity
      and produce a gastroprotective effect. The aim of the present study was to
      examine the effects of the interaction between docosahexaenoic acid (DHA) and
      diclofenac on inflammation (fixed ratios 1:1, 1:3, and 3:1), nociception (fixed
      ratio 1:3), and gastric injury in rats. DHA, diclofenac, or combinations of DHA
      and diclofenac produced anti-inflammatory and antinociceptive effects in rat. The
      administration of diclofenac produced significant gastric damage, but this effect
      was not observed with either DHA or the DHA-diclofenac combinations. Effective
      dose (ED30 ) values were estimated for each individual drug and analyzed
      isobolographically. The anti-inflammatory experimental ED30 values were 6.97
      mg/kg (1:1 fixed ratio), 1.1 mg/kg (1:3 fixed ratio), and 11.34 mg/kg (3:1 fixed
      ratio). These values were significantly lower (p < .05) than the theoretical ED30
      values: 67.94 mg/kg (1:1), 35.37 mg/kg (1:3), and 100.51 mg/kg (3:1). The
      antinociceptive experimental value was 1.25 mg/kg (1:3 fixed ratio). This value
      was lower (p < .05) than the theoretical ED30 , which was predicted to be 15.92
      mg/kg. These data indicate that the DHA-diclofenac combinations interact at the
      systemic level, produce minor gastric damage, and potentially have therapeutic
      advantages for the clinical treatment of inflammatory pain.

PMID- 30188587
TI  - Evaluation of samidorphan, a MU-opioid antagonist, in a drug discrimination assay
      in rats.
AB  - : Preclinical Research & Development Background: Samidorphan, a MU-opioid
      receptor antagonist, is in clinical development for central nervous system
      related diseases. The discriminative stimulus effects of samidorphan were
      assessed in rats trained to discriminate the effects of a known morphinan of
      abuse, morphine, from that of saline. METHODS: Escalating doses of samidorphan
      were substituted for morphine and rats were allowed to respond on two levers for
      food reward. Doses of samidorphan were chosen based on other pharmacodynamic
      assays in which samidorphan blocked the effects of morphine (such as blocking
      analgesia in a hot plate test; data not shown). In addition, a pharmacokinetic
      study was conducted to determine if these doses would reflect predicted exposure
      levels that translate to human equivalent doses. RESULTS: Rats discriminating
      morphine from vehicle responded predominantly on the vehicle lever after
      receiving samidorphan. In addition, samidorphan was rapidly absorbed, and plasma
      concentrations of the doses tested in this study bracket therapeutically relevant
      concentrations. CONCLUSIONS: In summary, samidorphan produced saline-like
      behavioral responses over a wide dose range.

PMID- 30188588
TI  - Mongolian Health Sector Strategic Master Plan (2006-2015): A foundation for
      achieving universal health coverage.
AB  - Nearly half of the countries in the world are in the process of reforming and
      strengthening their health care systems. More recently, even low-income and
      middle-income countries such as Mongolia have focused increasing attention on
      achieving universal health coverage (UHC). At this critical point, it is
      necessary to track recent progress and adjust health care strategies and
      planning. Therefore, this study analyzed changes in the health sector toward
      achieving UHC based on relevant literature, government documents, and framework
      analysis. We also investigated how basic principles of UHC were incorporated and
      reflected in Mongolia's Health Sector Strategic Master Plan. This study clarified
      the achievements of and challenges facing the health sector that remain or
      emerged during the plan's implementation over the last decade. Furthermore, all
      of the reviewed Master Plan strategies were underpinned by basic principles of
      UHC. However, strategies set out in the next Master Plan will require adjustments
      and innovative measures to respond to current challenges. This study may be used
      as a reference for other developing countries to track UHC achievements and serve
      as a guide to establishing a nation-wide strategic plan.

PMID- 30188590
TI  - Randomised controlled trial showed that neonates received better pain relief from
      a higher dose of sucrose during venepuncture.
AB  - AIM: We compared the effect of two different doses of sucrose on neonatal pain
      scores during venepuncture. METHODS: This randomised crossover study focused on
      neonates born weighing more than 1000 g from December 2014 to June 2016, who
      received neonatal intensive care at two hospitals: one in Empangeni, South
      Africa, and one in Trondheim, Norway. During two consecutive venepuncture
      procedures, 27 neonates from South Africa and 26 neonates from Norway were
      randomised to receive 0.2 mL or 0.5 mL sucrose. Half was administered two minutes
      before venepuncture and the rest immediately before the procedure. South Africa
      used 25% sucrose and Norway 24%. Pain scores were measured twice using the
      Premature Infant Pain Profile-Revised: during skin puncture and after the needle
      was removed. RESULTS: The mean pain scores during skin puncture were
      significantly lower with 0.5 mL sucrose than with 0.2 mL (5.3 versus 6.8,
      p=0.008), but the mean pain scores after the needle was removed were similar with
      both doses (4.7 versus 5.4, p=0.29). We found no significant association between
      weight and pain scores. CONCLUSION: We showed that neonates received better pain
      relief from 0.5 mL than 0.2 mL sucrose during venepuncture but not after the
      needle was removed.

PMID- 30188591
TI  - Long noncoding RNA opa-interacting protein 5 antisense transcript 1 promotes
      proliferation and invasion through elevating integrin alpha6 expression by
      sponging miR-143-3p in cervical cancer.
AB  - An increasing number of studies have shown that long noncoding RNAs (lncRNAs)
      play important roles in cervical cancer (CC) progression. However, the roles and
      underlying mechanisms of lncRNA opa-interacting protein 5 antisense transcript 1
      (OIP5-AS1) involved in the CC remain unclear. In the current study, we found that
      lncRNA OIP5-AS1 was upregulated in CC tissues and cell lines. High OIP5-AS1
      expression was significantly correlated with advanced International Federation of
      Gynecology and Obstetrics (FIGO) stage, lymph node metastasis, and poor overall
      survival of patients with CC. Using in vitro function assays, we showed that OIP5
      AS1 suppression significantly decreased the proliferation, colony formation, and
      invasion ability of CC cells. Moreover, we revealed that OIP5-AS1 could act as a
      competing endogenous RNA of miR-143-3p to regulate the ITGA6 expression. Rescue
      assays showed that miR-143-3p inhibitors or ITGA6 overexpression could reverse
      the inhibitory effects of OIP5-AS1 suppression on the proliferation and invasion
      in CC cells. In addition, OIP5-AS1 suppression reduced tumor growth in vivo. In
      conclusion, we demonstrated that OIP5-AS1 promoted proliferation and invasion of
      CC cells via increasing the ITGA6 expression by sponging miR-143-3p, which might
      be an effective therapeutic target for the treatment of patients with CC.

PMID- 30188589
TI  - General retrospective mega-analysis framework for rare variant association tests.
AB  - Here, we describe a retrospective mega-analysis framework for gene- or region
      based multimarker rare variant association tests. Our proposed mega-analysis
      association tests allow investigators to combine longitudinal and cross-sectional
      family- and/or population-based studies. This framework can be applied to a
      continuous, categorical, or survival trait. In addition to autosomal variants,
      the tests can be applied to conduct mega-analyses on X-chromosome variants. Tests
      were built on study-specific region- or gene-level quasiscore statistics and,
      therefore, do not require estimates of effects of individual rare variants. We
      used the generalized estimating equation approach to account for complex multiple
      correlation structures between family members, repeated measurements, and genetic
      markers. While accounting for multilevel correlations and heterogeneity across
      studies, the test statistics were computationally efficient and feasible for
      large-scale sequencing studies. The retrospective aspect of association tests
      helps alleviate bias due to phenotype-related sampling and type I errors due to
      misspecification of phenotypic distribution. We evaluated our developed mega
      analysis methods through comprehensive simulations with varying sample sizes,
      covariates, population stratification structures, and study designs across
      multiple studies. To illustrate application of the proposed framework, we
      conducted a mega-association analysis combining a longitudinal family study and a
      cross-sectional case-control study from Genetic Analysis Workshop 19.

PMID- 30188592
TI  - Bone and joint infections in infants under three months of age.
AB  - AIM: Studies on bone and joint infections (BJI) in infants under three months are
      rare. We described the clinical and paraclinical features and outcomes of infants
      hospitalised with BJI under three months of age. METHODS: The French National
      Hospital Discharge Database provided data on BJIs in infants under three months
      of age from January 2004 to 2015 in three Parisian Paediatric teaching hospitals.
      RESULTS: We included 71 infants under three months of age with BJI, the median
      age was 25 days, and the interquartile range (IQR) was 17-43 days. The most
      common infection sites were the hip (32%) and knee (32%). Symptoms included pain
      (94%), limited mobility (87%) and/or fever (52%). There were 11 (15.5%) cases of
      nosocomial BJI. A pathogen was identified in 51 infants (71.8%), including
      Streptococcus agalactiae (45%), Staphylococcus aureus (22%) and Escherichia coli
      (18%). The initial median C-reactive protein test rate was 31 mg/L (IQR 17-68).
      Of the 34 infants followed for more than one year, four developed severe
      orthopaedic conditions such as epiphysiodesis, limb length discrepancy, bone
      necrosis and/or impaired limb function. CONCLUSION: Streptococcus agalactiae was
      the most common cause of BJI in infants under three months. Orthopaedic sequelae
      were rare, but severe, and required long-term follow-up.

PMID- 30188593
TI  - Complex-precipitation using functionalized chiral ionic liquids with L-proline
      anion and chromatographic analysis for enantioseparation of racemic amino acids.
AB  - As one kind of functionalized green medium, chiral ionic liquids (CILs) have been
      widely applied in fields of asymmetric catalysis, enantioseparation, and so on.
      In this study, four kinds of amino acid-based CILs were synthesized by using
      trimethylamine, N-methylpyrrolidine, N-methylimidazole, and tropine as cationic
      nucleus, respectively. Then their specific optical rotation and solubility in
      common solvents were determined for further resolution application. The effect of
      different cations in these CILs was explored on the separation of racemic
      phenylalanine in complex-precipitation way. Moreover, various factors were
      systematically investigated for their effects on resolution efficiency, including
      the type of additive copper salts, the molar ratio of Cu (II) to CIL, pH value,
      the amount of racemic phenylalanine, and temperature. Under the appropriate
      conditions, L-phenylalanine mainly existed in solid phase and could be separated
      from its enantiomers in liquid phase. Furthermore, the mechanism of resolution
      was studied by thermogravimetric analysis, infrared spectrum, and molecular
      simulation. The resolution system has characteristics of no organic solvent, fast
      separation speed, simple resolution process, and easy scale-up.

PMID- 30188594
TI  - A mini-review and implementation model for using ataluren to treat nonsense
      mutation Duchenne muscular dystrophy.
AB  - AIM: Ataluren has been approved for treating nonsense mutation Duchenne muscular
      dystrophy (nmDMD), and there are currently discussions concerning drug access and
      applications beyond the development programme. This study provides an overview of
      nmDMD and ataluren, stipulates clinical rules for treatment initiation and
      discontinuation and proposes a model for the implementation of orphan drugs in
      clinical practice in Sweden. METHODS: This was a targeted mini-review of the
      literature from 1995 to 2018, which included cohort studies, guidelines,
      randomised clinical trials, clinical commentaries and reviews. The review covered
      the pathophysiology, epidemiology and burden of nmDMD and the clinical programme
      for ataluren. RESULTS: Based on the current evidence, and our experiences, we
      recommend that patients with nmDMD should be given ataluren as soon as possible
      after diagnosis and this treatment should continue until they reach a forced
      vital capacity of <30%, and, or, a score of at least six on the Brooke upper
      extremity scale. We propose an implementation model that comprises a coordinating
      specialist physician and a national expert committee responsible for providing
      clinical intelligence to ensure appropriate use. CONCLUSION: Our clinical
      recommendations and proposed implementation model will inform the optimum medical
      management of nmDMD in Sweden and help ensure timely, equal access to ataluren
      and similar orphan drugs.

PMID- 30188596
TI  - Colour Flow Mapping examination: An useful screening test for the early diagnosis
      of ductus venosus patency in canine newborns.
AB  - Ductus venosus (DV) closure plays a key role in hepatic circulation adaptation to
      postnatal metabolic function, and DV patency might develop a congenital
      portosystemic shunt (CPSS). The noninvasive Color Flow Mapping (CFM) examination,
      a validated method to diagnose CPSS in adult dogs, is routinely performed to
      assess DV closure after birth in humans. This study aimed to describe the
      feasibility of the ultrasonographic evaluation of the DV after birth and to
      determine its closure time in healthy Great Dane neonates. Patency of DV in
      serial Color Flow Mapping (CFM) examinations and bodyweight (BW) were recorded on
      Days 0-3-6-9 in 24 neonates that were classified as having patent (PDV) or closed
      ductusvenosus (CDV) basing on CFM signal presence/absence. Since the 3rd day, DV
      diameter was recorded. Data were analysed by ANOVA (p < 0.05). All dogs resulted
      healthy 1 year later. The number of PDV and CDV puppies at birth was not
      different on Day 3 (24 and 0 vs. 22 and 2, PDV and CDV, respectively), whereas it
      resulted different on Days 6 (24 and 0 vs. 14 and 10) and 9 (24 and 0 vs. 0 and
      24); on Day 3, it was different compared to Days 6 and 9; on Day 6, it was
      different from Day 9. Reduction of DV diameter resulted positively related to
      neonatal BW growth. The CFM evaluation of DV closure after birth in Great Dane
      puppies represents a feasible technique. Present results suggest the time of
      functional closure in normal neonates within 9 days after birth. Thus, CFM
      examination, as an early screening test for DV patency evaluation, performed 10
      days after birth, may identify suspicious dogs at risk that would require further
      investigations. Further studies are needed to deepen the role of a delayed
      closure in low bodyweight and preterm puppies.

PMID- 30188597
TI  - Mystery of rhythmic signal emergence within the suprachiasmatic nuclei.
AB  - The circadian system provides organisms with a temporal organization that
      optimizes their adaptation to environmental fluctuations on a 24-hr basis. In
      mammals, the circadian clock in the suprachiasmatic nuclei (SCN) develops during
      the perinatal period. The rhythmicity first appears at the level of individual
      SCN neurons during the fetal stage, and this step is often misinterpreted as the
      time of complete SCN clock development. However, the process is only finalized
      when the SCN begin to play a role of the central clock in the body, that is, when
      they are able to generate robust rhythmicity at the cell population level,
      entrain the rhythmic signal with external light-dark cycles and convey this
      signal to the rest of the body. The development is gradual and correlates with
      morphological maturation of the SCN structural complexity, which is based on
      intercellular network formation. The aim of this review is to summarize events
      related to the first emergence of circadian oscillations in the fetal SCN clock.
      Although a large amount of data on ontogenesis of the circadian system have been
      accumulated, how exactly the immature SCN converts into a functional central
      clock has still remained rather elusive. In this review, the hypothesis of how
      the SCN attains its rhythmicity at the tissue level is discussed in context with
      the recent advances in the field. For an extensive summary of the complete
      ontogenetic development of the circadian system, the readers are referred to
      other previously published reviews.

PMID- 30188595
TI  - The novel regulatory role of lncRNA-miRNA-mRNA axis in cardiovascular diseases.
AB  - Long noncoding RNAs (lncRNAs) are RNAs longer than 200 nt in length that are
      characterized by low levels of sequence conservation and expression; lncRNAs
      modulate various biological functions at epigenetic, transcriptional and post
      transcriptional levels, or directly regulate protein activity. As a family of
      small and evolutionarily conserved noncoding RNAs, microRNAs (miRNAs) are capable
      of regulating physiological and pathological processes via inhibiting target mRNA
      translation or promoting mRNA degradation. A number of studies have confirmed
      that both lncRNAs and miRNAs are closely associated with the development of
      cardiovascular diseases (CVDs), such as cardiac remodelling, heart failure,
      myocardial injury and arrhythmia, and that they act as biomarkers, potential
      therapeutic targets or strong indicators of prognosis; however, the underlying
      molecular mechanism has not been elucidated. Recently, emerging evidence showed
      that the novel regulatory mechanism underlying the crosstalk among lncRNAs,
      miRNAs and mRNAs plays a pivotal role in the pathophysiological processes of CVDs
      in response to stress stimuli. In this review, I comprehensively summarized the
      regulatory relationship of lncRNAs, miRNAs and mRNAs and highlighted the
      important role of the lncRNA-miRNA-mRNA axis in CVDs.

PMID- 30188598
TI  - The prevalence and predictors of mental health diagnoses and suicide among U.S.
      college students: Implications for addressing disparities in service use.
AB  - BACKGROUND: The college years represent a period of increased vulnerability for a
      wide range of mental health (MH) challenges. The onset of common psychiatric
      conditions occurs during this period of development. Increases in depression,
      anxiety, and suicidality among U.S. college students have been observed. This
      study identified prevalence and correlates of MH diagnoses and suicidality in a
      recent sample of U.S. college students. METHODS: The Spring 2015 American College
      Health Association-National College Health Assessment (ACHA-NCHA) survey assessed
      MH diagnoses and suicidality from U.S. undergraduate students (n = 67,308) across
      108 institutions. RESULTS: Stress was strongly associated with a greater
      likelihood of suicide attempts and MH diagnoses, even among students reporting 1
      2 stressful events (OR [odds ratio] range 1.6-2.6, CI [confidence interval] = 1.2
      3.2). Bisexual students were more likely to report MH diagnoses and suicidality,
      compared to heterosexual and gay/lesbian students (OR range 1.5-3.9, CI = 1.8
      4.3), with over half engaging in suicidal ideation and self-harm, and over a
      quarter reporting suicide attempts. Transgender students reported a higher rate
      of MH diagnoses and suicidality relative to females (OR range 1.9-2.4, CI = 1.1
      3.4). Racial/ethnic minority students were generally less likely to report MH
      diagnoses relative to Whites, although the likelihood for suicidality was mixed.
      CONCLUSIONS: The high rate of multiple stress exposures among the U.S. college
      population and the high impacts of stress on MH and suicidality point to an
      urgent need for service utilization strategies, especially among racial/ethnic,
      sexual, or gender minorities. Campuses must consider student experiences to
      mitigate stress during this developmental period.

PMID- 30188599
TI  - Hiding in Plain Sight: Nebivolol Exhibits Compelling Tocolytic Properties.
AB  - Preterm birth before 37 weeks of completed gestation results in numerous health
      consequences for the foetus. Preterm labour leads to preterm birth in over 50% of
      cases, and no FDA-approved treatment can prevent labour or help a foetus remain
      in the womb until term. Examination of nitric oxide mediated relaxation signaling
      in the uterine smooth muscle reveals a role for protein S-nitrosation. The recent
      discovery of upregulated S-nitrosoglutathione reductase (GSNOR) in spontaneously
      preterm labouring women has emphasized the need to explore the function of S
      nitrosation regulation in the maintenance of uterine quiescence. Here we have
      examined the ability of nebivolol to relax uterine smooth muscle and tested
      recent claims that nebivolol is a GSNOR inhibitor. In uterine smooth muscle
      strips from both mouse and human, nebivolol relaxes oxytocin-induced contractions
      in a dose dependent manner. Our data indicates that nebivolol has no effect on
      GSNOR activity, nor does nebivolol inhibit thioredoxin reductase, two of the
      major protein denitrosylases. The ability of nebivolol to relax uterine smooth
      muscle is likely the combined effects of increased nitric oxide synthase activity
      and beta3-adregnegic stimulation.

PMID- 30188600
TI  - Aflatoxin B1 adsorption/desorption dynamics in the presence of Lactobacillus
      rhamnosus RC007 in a gastrointestinal tract-simulated model.
AB  - AIMS: (i) To determine the aflatoxin B1 (AFB1 ) adsorption and desorption
      dynamics in the presence of Lactobacillus rhamnosus RC007 under simulated transit
      of AFB1 at each gastrointestinal tract (GIT-saliva, stomach and intestine) stage
      consecutively and then, separately, (ii) to study the ability of L. rhamnosus
      RC007 to biotransform AFB1 as a strategy that complements the adsorption process.
      METHODS AND RESULTS: The AFB1 adsorption and desorption assay simulating the GIT
      passage of AFB1 (93.89 ng g-1 ) in the presence of L. rhamnosus RC007 (108 CFU
      per ml) was conducted. Moreover, lactic acid production was determined. Results
      demonstrated that predominant environmental conditions in salivary solution
      induced a low AFB1 adsorption, while the transit through the gastric solution and
      intestinal solution allowed high percentages of adsorption and did not generate
      significant AFB1 desorption. CONCLUSIONS: The AFB1 adsorption and desorption
      dynamics in the presence of L. rhamnosus RC007 was favoured by gastric and
      intestinal environment. SIGNIFICANCE AND IMPACT OF THE STUDY: The knowledge of
      the adsorption dynamics of AFB1 with a micro-organism of interest will allow
      predicting its behaviour at each stage of the GIT.

PMID- 30188601
TI  - Long-term outcomes in 1121 Australian prostate cancer patients treated with
      definitive radiotherapy.
AB  - INTRODUCTION: Optimal definitive treatment of prostate cancer is controversial,
      especially in high-risk patients. We report the largest prospective cohort of
      Australian patients treated with radiotherapy for localised prostate cancer.
      METHODS: One thousand, one hundred and twenty-one patients with prostate cancer
      were prospectively registered and treated to a dose of 70-74 Gy. Patients were
      classified as low, intermediate or high risk based on PSA, clinical staging and
      Gleason score. Intermediate-risk patients were treated with 0-6 months of
      hormonal therapy (ADT) and high-risk patients were offered neoadjuvant and
      adjuvant ADT. Overall survival (OS) and biochemical relapse-free survival (bNED)
      were calculated using the Kaplan-Meier method. RESULTS: Median follow-up was 92
      months. Eight-year OS and bNED were 78.4% and 68.1% respectively in the entire
      cohort. OS for the low, intermediate and high-risk groups was 84.5%, 78.4% and
      68% respectively. For these risk groups, bNED was 80.3%, 65.7% and 53.7%
      respectively. In the intermediate and high-risk group, OS and bNED decreased with
      increasing number of risk factors. CONCLUSION: Definitive radiotherapy is an
      effective treatment for prostate cancer, including in high-risk cases.

PMID- 30188602
TI  - Comparative responsiveness of generic versus disorder-specific instruments for
      depression: An assessment in three longitudinal datasets.
AB  - BACKGROUND: Routine outcome monitoring (ROM) may enhance individual treatment and
      is also advocated as a means to compare the outcome of different treatment
      programs or providers. There is debate on the optimal instruments to be used for
      these separate tasks. METHODS: Three sets with longitudinal data from ROM were
      analyzed with correlational analysis and repeated measures ANOVAs, allowing for a
      head-to-head comparison of measures regarding their sensitivity to detect change.
      The responsiveness of three disorder-specific instruments, the Beck Depression
      Inventory, the Inventory of Depressive Symptoms, and the Mood and Anxiety
      Symptoms Questionnaire, was compared to three generic instruments, the Symptom
      Checklist (SCL-90), the Outcome Questionnaire (OQ-45), and the Brief Symptom
      Inventory, respectively. RESULTS: In two of the three datasets, disorder-specific
      measures were more responsive compared to the total score on generic instruments.
      Subscale scores for depression embedded within generic instruments are second
      best and almost match disorder-specific scales in responsiveness. No evidence of
      a desynchronous response on outcome measures was found. LIMITATIONS: The present
      study compares measures head-to-had, and responsiveness is not assessed against
      an external criterion, such as clinical recovery. DISCUSSION: Disorder-specific
      measures yield the most precise assessment for individual treatment and are
      recommended for clinical use. Generic measures may allow for comparisons across
      diagnostic groups and their embedded subscales approach the responsiveness of
      disorder-specific measures.

PMID- 30188603
TI  - Time to take on HPV in transplant clinic - Warts and all.

PMID- 30188604
TI  - Positive familial history for metabolic traits predisposes to early and more
      severe alcoholic cirrhosis: A cross-sectional study.
AB  - BACKGROUND & AIMS: Familial aggregation of metabolic traits in NAFLD is well
      documented. However, relevance of these traits in alcoholic cirrhosis is not well
      studied. We aimed to explore the association of family history of metabolic
      traits with age at diagnosis, severity and complications of alcoholic cirrhosis.
      METHODS: In a cross-sectional study, all consecutive patients with alcoholic
      cirrhosis presenting to our tertiary care centre were included. Family and
      personal history, demographic characteristics, medical history, anthropometric
      measurements and laboratory data were recorded. The amount and duration of
      alcohol consumption were also carefully recorded. RESULTS: Out of 1084 alcoholic
      cirrhotics (age 48.5 +/- 10.1 years, all males), family history for metabolic
      traits was documented in 688 (63.5%) patients. These patients had younger age at
      diagnosis, increased incidence of jaundice, ascites, variceal bleed and hepatic
      encephalopathy with consequently higher MELD and CTP score. These patients
      developed cirrhosis despite shorter median duration (13 years, IQR 7-20 vs 21,
      IQR 18-25) and lesser amount of alcohol consumption (74 g/d, IQR 24-96 vs 144,
      IQR 100-148). Patients with both family and personal history of metabolic traits
      had a higher risk by 3.3 times (95% CI 2.2-4.8) of an early age at diagnosis,
      13.2 times (95% CI 8.7-20.1) of progression to cirrhosis with lesser amount of
      alcohol consumption and 4.6 times (95% CI 3.1-6.9) with lesser duration of
      alcohol consumption. CONCLUSIONS: Positive family and personal history of
      metabolic traits predispose to alcoholic cirrhosis with an earlier age at onset
      and more severity despite lesser exposure to alcohol.

PMID- 30188606
TI  - Type 1 Laryngeal Cleft and feeding and swallowing difficulties in infants and
      toddlers: A Review.

PMID- 30188605
TI  - phlda3 overexpression impairs specification of hemangioblasts and vascular
      development.
AB  - The phlda3 gene encodes a small, 127-amino acid protein with only a PH domain,
      and is involved in tumor suppression, proliferation of islet beta-cells, insulin
      secretion, glucose tolerance, and liver injury. However, the role of phlda3 in
      vascular development is unknown. Here, we show that phlda3 overexpression
      decreases the expression levels of hemangioblast markers scl, fli1, and etsrp and
      intersegmental vessel (ISV) markers flk1 and cdh5, and disrupts ISV development
      in tg(flk1:GFP) and tg(fli1:GFP) zebrafish. Moreover, phlda3 overexpression
      inhibits the activation of protein kinase B (AKT) in zebrafish embryos, and the
      developmental defects of ISVs by phlda3 overexpression were reversed by the
      expression of a constitutively active form of AKT. These data suggest that phlda3
      is a negative regulator of hemangioblast specification and ISV development via
      AKT signaling.

PMID- 30188607
TI  - Intrapatient variability in solid organ transplantation: Should we make the first
      move earlier?

PMID- 30188609
TI  - The potential contribution and role of a blood platelets in autoimmune thyroid
      diseases.
AB  - The blood platelets are multifunctional blood cells which are involved in the
      initiation of atheroma, endothelial dysfunction, and modulation of inflammatory
      and immune responses in the pathophysiology of many diseases. Because of their
      multifaceted pro-inflammatory activity, platelets may be involved in the
      pathogenesis of autoimmune thyroid diseases (AITDs), such as Hashimoto's
      thyroiditis and Graves' disease. The aim of this study was to assess the level of
      activation and response ability of platelets in AITDs. We used the flow cytometry
      technique and kinetic measurement of aggregation to analyse platelet function
      immediately after blood collection and to demonstrate their activation in the
      circulation of patients with AITDs. We noted reorganization of platelet
      subpopulations (normal platelets, microparticles and aggregates) in AITDs,
      dependent on the degree of cell activation. We proved the elevated expression of
      the active form of integrin receptor GPIIb/IIIa, responsible for platelet
      aggregation, and in the kinetic test we confirmed the increased aggregation of
      platelets in different intracellular signal pathways (dependent on ADP, collagen,
      arachidonic acid). Our study demonstrates the high platelet activation level
      found in AITDs.

PMID- 30188608
TI  - Kinematic boundary conditions substantially impact in silico ventricular
      function.
AB  - Computational cardiac mechanical models, individualized to the patient, have the
      potential to elucidate the fundamentals of cardiac (patho-)physiology, enable non
      invasive quantification of clinically significant metrics (eg, stiffness, active
      contraction, work), and anticipate the potential efficacy of therapeutic
      cardiovascular intervention. In a clinical setting, however, the available
      imaging resolution is often limited, which limits cardiac models to focus on the
      ventricles, without including the atria, valves, and proximal arteries and veins.
      In such models, the absence of surrounding structures needs to be accounted for
      by imposing realistic kinematic boundary conditions, which, for prognostic
      purposes, are preferably generic and thus non-image derived. Unfortunately, the
      literature on cardiac models shows no consistent approach to kinematically
      constrain the myocardium. The impact of different approaches (eg, fully
      constrained base, constrained epi-ring) on the predictive capacity of cardiac
      mechanical models has not been thoroughly studied. For that reason, this study
      first gives an overview of current approaches to kinematically constrain (bi)
      ventricular models. Next, we developed a patient-specific in silico biventricular
      model that compares well with literature and in vivo recorded strains.
      Alternative constraints were introduced to assess the influence of commonly used
      mechanical boundary conditions on both the predicted global functional behavior
      of the in-silico heart (cavity volumes, stroke volume, ejection fraction) and
      local strain distributions. Meaningful differences in global functioning were
      found between different kinematic anchoring strategies, which brought forward the
      importance of selecting appropriate boundary conditions for biventricular models
      that, in the near future, may inform clinical intervention. However, whilst
      statistically significant differences were also found in local strain
      distributions, these differences were minor and mostly confined to the region
      close to the applied boundary conditions.

PMID- 30188610
TI  - Obesity in the global haemophilia population: prevalence, implications and expert
      opinions for weight management.
AB  - Overweight and obesity may carry a significant disease burden for patients with
      haemophilia (PWH), who experience reduced mobility due to joint inflammation,
      muscle dysfunction and haemophilic arthropathy. This review aimed to define the
      prevalence and clinical impact of overweight/obesity in the global population of
      PWH. A detailed literature search pertaining to overweight/obesity in haemophilia
      in the last 15 years (2003-2018) was conducted, followed by a meta-analysis of
      epidemiological data. The estimated pooled prevalence of overweight/obesity in
      European and North American PWH was 31%. Excess weight in PWH is associated with
      a decreased range in motion of joints, accelerated loss of joint mobility and
      increase in chronic pain. Additionally, the cumulative disease burden of obesity
      and haemophilia may impact the requirement for joint surgery, occurrence of
      perioperative complications and the prevalence of anxiety and depression that
      associates with chronic illness. Best practice guidelines for obesity prevention
      and weight management, based on multidisciplinary expert perspectives, are
      considered for adult and paediatric PWH. Recommendations in the haemophilia
      context emphasize the importance of patient education and tailoring engagement in
      physical activity to avoid the risk of traumatic bleeding.

PMID- 30188613
TI  - Maastricht Pathology 2018. 11th Joint Meeting of the British Division of the
      International Academy of Pathology and the Pathological Society of Great Britain
      & Ireland, 19-22 June 2018.

PMID- 30188611
TI  - Generation of the UFM1 Toolkit for Profiling UFM1-Specific Proteases and Ligases.
AB  - Ubiquitin-fold modifier 1 (UFM1) is a reversible post-translational modifier that
      is covalently attached to target proteins through an enzymatic cascade and
      removed by designated proteases. Abnormalities in this process, referred to as
      Ufmylation, have been associated with a variety of human diseases. Given this,
      the UFM1-specific enzymes represent potential therapeutic targets; however,
      understanding of their biological function has been hampered by the lack of
      chemical tools for activity profiling. To address this unmet need, a
      diversifiable platform for UFM1 activity-based probes (ABPs) utilizing a native
      chemical ligation (NCL) strategy was developed, enabling the generation of a
      variety of tools to profile both UFM1 conjugating and deconjugating enzymes. The
      use of the probes is demonstrated in vitro and in vivo for monitoring UFM1 enzyme
      reactivity, opening new research avenues.

PMID- 30188614
TI  - The survival advantage of pancreas after kidney transplant.
AB  - Patient survival after pancreas after kidney transplant (PAK) has been reported
      to be inferior to patient survival after simultaneous pancreas-kidney transplant
      (SPK). The authors examine national data to further explore allograft (kidney and
      pancreas) and patient survival after PAK. Kaplan-Meier and Cox proportional
      hazard models were used to analyze Organ Procurement and Transplantation Network
      data from 1995 to 2010. The analysis compared PAK and SPK candidates and
      recipients. Kaplan-Meier analysis results showed that PAK after either a living
      or a deceased donor kidney transplant is associated with increased kidney graft
      survival compared with recipients with type 1 diabetes who received only a
      kidney. The best kidney allograft survival was for patients who received a living
      donor kidney followed by PAK. Receiving a living donor kidney was associated with
      increased pancreas allograft survival compared with receiving a deceased donor
      kidney. PAK transplant recipients who receive both organs have a survival
      advantage compared with uremic candidates who receive neither (SPK waitlist).
      Compared with uremic diabetic waitlist patients, SPK and PAK recipients showed
      similar overall patient survival. Successful PAK offers a survival advantage
      compared with receiving neither a kidney nor a pancreas transplant. These data
      also suggest that receiving a pancreas (after kidney) transplant may have a
      protective effect on the kidney allograft.

PMID- 30188612
TI  - The kruppel-like factor Dar1 restricts the proliferation of Drosophila intestinal
      stem cells.
AB  - The kruppel-like factors (KLFs) are a family of transcription factor proteins
      that regulate a wide range of biological processes. In an RNAi-based screening
      experiment, we identified dendritic arbor reduction 1 (Dar1), which is a KLF
      member in Drosophila, that inhibited the proliferation of intestinal stem cells
      (ISCs). We found suppression of Dar1-activated ISC proliferation; as a
      consequence, the ISCs and the young differentiated cells were increased. On the
      other hand, overexpression (OE) of Dar1 inhibited ISC division and blocked the
      formation of ISC lineages. In order to explore the molecular mechanism of the
      Dar1 functions, we compared the gene expression profiles of the Dar1 knockdown
      and Dar1 OE midguts, using the deep RNA sequencing (RNA-Seq) technique. This
      experiment revealed that Dar1 negatively regulated the expression of several
      critical cell cycle genes. We further provide evidence that Dar1 has a function
      upstream of the JAK/STAT signaling pathway, suggesting Dar1 can regulate ISC
      proliferation through different mechanisms. Consistent with these findings, we
      discovered that Dar1 was downregulated in the wounded midguts, allowing increased
      ISC proliferation to promote intestinal repair. Our data suggest that Dar1 is a
      functional homolog of the mammalian KLF4.

PMID- 30188615
TI  - Why might patients in the UK consult a general medical practitioner when
      experiencing dental problems? A literature review of patients' perspectives.
AB  - OBJECTIVE: to systematically appraise and synthesise the existing evidence
      regarding the reasons why patients in the UK may consult a general medical
      practitioner (GMP) when experiencing a dental problem. BASIC RESEARCH DESIGN: a
      systematic review of the scientific and grey literature published between 1996
      and 2017. PARTICIPANTS: dental service users (adults or children) from the UK
      and/or their carers who were seeking, or had sought, care for a dental problem
      from a GMP. MAIN OUTCOMES: patients' perspectives on reasons for consulting a GMP
      were qualitatively synthesised according to Levesque et al.'s conceptual
      framework of access to health care. RESULTS: Out of 1,232 references screened, 2
      studies met the inclusion criteria for the review. They identified the following
      factors that can influence care-seeking for dental problems: patients'
      interpretation of their symptoms; their understanding of practitioners' scope of
      practice; the availability of timely dental care; and the affordability of care.
      Both studies had weaknesses with regard to either their conduct and/or reporting.
      CONCLUSIONS: Choice of practitioner for dental problems is likely to be
      influenced by both the beliefs and attitudes of the individual patient and the
      organisation and attributes of the providers of dental and medical care. However,
      in light of the quality of the existing evidence base, there is a need for high
      quality studies exploring the reasons why patients in the UK may seek care from a
      GMP when experiencing dental problems.

PMID- 30188616
TI  - A multi-variable analysis of four factors affecting caries levels among five-year
      old children; deprivation, ethnicity, exposure to fluoridated water and
      geographic region.
AB  - OBJECTIVE: To assess the role of factors posited to affect population caries
      levels across England. BASIC RESEARCH DESIGN: Multivariable regression analysis
      assessing four potential determinants of caries severity and prevalence:
      deprivation, exposure to fluoridated water, ethnicity and geographic region
      Participants: Random sample of 121,875 five-year-old children in England in the
      2014/15 academic year. MAIN OUTCOME MEASURES: Decayed, missing and filled teeth,
      with decay measured at the dentinal level, (d3mft), presented as prevalence
      (dmft?0) and extent of decay among children who have any (d3mft if d3mft>0).
      INDEPENDENT VARIABLES: Parental reported ethnicity from school records, index of
      multiple deprivation (IMD) scores, region and exposure to water fluoridation
      calculated utilising home postcodes. RESULTS: The data support wider literature
      displaying associations between caries and deprivation across a social gradient.
      The important, new findings are deprivation, some ethnic groups and lack of
      exposure to water fluoridation are all associated with increased prevalence and
      severity of caries when considered together and independently. New evidence
      supports the impact of water fluoridation on health inequalities in that the
      greatest impact of exposure to fluoridated water was seen in the most deprived
      children and those from an Asian / Asian British ethnic group. CONCLUSIONS: Five
      year-old children who were from the most deprived areas, not exposed to
      fluoridated water, of an Eastern European ethnic group and living in the North
      West demonstrated the highest prevalence and severity of caries in the survey
      under scrutiny. This is of public health importance, providing evidence for
      population groups to target with health improvement activities.

PMID- 30188617
TI  - Results of cross-faculty 'capstone' assessments involving nursing and performing
      arts students.
AB  - This article describes how 'capstone' assessments were created to provide two
      different student groups, nursing and performing arts students, with a lived
      experience of learning together about their own fields of practice. Capstone
      assessments combine 'live' human simulation with self-reflection and peer review.
      A capstone assessment is the integration of a body of relatively fragmented
      knowledge and learning to form a unified whole and can be used as a transitional
      assessment and a bridging experience to connect knowledge between modules or
      courses. The capstone assessments involved two faculties and four modules, three
      nursing and one performing arts. Case studies were designed to represent real
      life situations that students were likely to encounter during their careers,
      either playing a patient as an actor or performing a caring role as a nurse.
      Assessments for the capstone simulation were formative, and involved the students
      engaging in self-reflection and peer review. Videos were available to enhance the
      self-reflection and peer-review process. Evaluation was undertaken through verbal
      feedback during debrief, written feedback, video footage and nursing student and
      acting student peer review. The experience of capstone assessments for two
      diverse student groups provided valuable learning from their own and from a
      different group outside their subject area.

PMID- 30188618
TI  - CHLOROQUINE DOES NOT CANCEL E1A+cHa-Ras TRANSFORMANTS' DEATH INDUCED BY mTOR
      KINASE INHIBITOR pp242..
AB  - We have studied the dependence of cell viability on cell autophagy in control and
      senescent E1A+cHa-Ras transformed rat embryo fibroblasts. pp242, a TORC1/C2
      kinase inhibitor, was used as a trigger of cell autophagy. Cell senescence was
      induced in the cells by sodium butyrate. pp242 inhibitor occurred to dramatically
      reduce the functional activity of mitochondria in intact cells causing their
      death by mitophagy and apoptosis. The presence of chloroquine that blocks
      lysosome and autophagosome fusion does not cancel pp242 effects. Senescent cells
      were more resistant to pp242 than control ones. However, their viability was
      significantly reduced in the presence of chloroquine and pp242. Thus, our results
      allow us to consider that the usage of chloroquine and pp242 combination is an
      effective way of cell death induction in intact and senescent Ras-transformants.

PMID- 30188619
TI  - EVALUATION OF EFFECTIVENESS OF SYNCHRONIZATION METHODS OF CELL DIVISION IN YEAST
      SACCHAROMYCES CEREVISIAE.
AB  - Synchronization of cell division in cultures of yeast Saccharomyces cerevisiae is
      widely used in research on the regulation of gene expression and biochemical
      processes in eukaryotes at different stages of the cell cycle. Here, we compare
      the efficiency of modern most commonly used methods to achieve and assess the
      degree of synchronization of cell division in yeast. Block-and-release methods
      with alpha-factor, hydroxyurea, nocodazole, cdc28-4 mutation are described in
      detail with practical notes.

PMID- 30188620
TI  - MEK/ERK-PATHWAY IS REQUIRED TO MAINTAIN CYTOPROTECTIVE AUTOPHAGY PROCESS IN
      IRRADIATED E1A+cHa-Ras TRANSFORMANTS.
AB  - Autophagy is a conservative process of misfolded protein and damaged organelle
      degradation that serves to support cellular viability. Autophagy is often induced
      in response to stress, DNA damage, retinoids, starvation and growth factor
      withdrawal. The aim of the present work was to study autophagic response of
      E1A+cHa-Ras-transformed cells to irradiation and to analyze the role of MEK/ERK
      pathway in regulation of autophagy induced by irradiation. MEK/ERK suppression
      has been found to decrease the viability of irradiated cells. Inhibition of
      MEK/ERK pathway leads to the changes in the autophagy induced by irradiation
      connected with disturbances of final stages followed by accumulation of adaptor
      protein p62/SQSTM1 in autophagic cavities within cytoplasm. Thus, the data
      obtained allow to suggest that active MEK/ERK pathway is required to support, the
      cytoprotective autophagy which is induced in response to irradiation of
      transformed E1A+cHa-ras cells.

PMID- 30188621
TI  - CHLOROQUINE DOES NOT CANCEL E1A+cHa-Ras TRANSFORMANTS' DEATH INDUCED BY mTOR
      KINASE INHIBITOR pp242.
AB  - We have studied the dependence of cell viability on cell autophagy in control and
      senescent E1A+cHa-Ras transformed rat embryo fibroblasts. pp242, a TORC1/C2
      kinase inhibitor, was used as a trigger of cell autophagy. Cell senescence was
      induced in the cells by sodium butyrate. pp242 inhibitor occurred to dramatically
      reduce the functional activity of mitochondria in intact cells causing their
      death by mitophagy and apoptosis. The presence of chloroquine that blocks
      lysosome and autophagosome fusion does not cancel pp242 effects. Senescent cells
      were more resistant to pp242 than control ones. However, their viability was
      significantly reduced in the presence of chloroquine and pp242. Thus, our results
      allow us to consider that the usage of chloroquine and pp242 combination is an
      effective way of cell death induction in intact and senescent Ras-transformants.

PMID- 30188622
TI  - CHANGES IN ERYTHROCYTE CA2+-ATPASE ACTIVITY UNDER PEG-1500 AND LOW TEMPERATURE
      INFLUENCE.
AB  - During cryopreservation different organic compounds are applied. Their
      introduction into cell suspension causes modification of subcellular systems and
      provides cell survival during freeze-thawing. The aim of the study was to
      determine the modifying effect of cryoprotectant PEG-1500 and low temperatures on
      the Ca2+-ATPase activity using the model of the saponin-permeabilized
      erythrocytes. PEG-1500 was found to cause the inhibition of erythrocytes Ca2+
      ATPase activity despite the presence in the medium of endogenous effectors
      capable of stimulating the enzyme function. Modification of Ca2+-ATPase is
      apparently due to the physical and chemical parameters of the cryoprotectant
      solution since the removal of the polymer out of the medium leads to recovery of
      its functional properties. The reversibility of the inhibition of Ca2+-ATPase is
      characteristic for erythrocytes exposed to the cryoprotectant without freezing as
      well as for those that have been frozen and thawed in the presence of PEG-1500.
      The processes of freezing-thawing of cells in the cryoprotectant-free medium did
      not affect the Ca2+-ATPase activity indicating cryoresistance of the membrane
      bond enzyme. Despite the fact that the efficiency of erythrocyte cryopreservation
      with PEG-1500 depends on incubation temperature prior to freezing, functional
      induces of Ca2+-ATPase activity in the erythrocytes exposed to PEG-1500 at 37 of
      5-7  degrees C show no significant differences when subsequent ATP hydrolyses
      reaction is carried out at 37  degrees C. However, reduction in the temperature
      upon enzymatic reaction progression down to 5-7  degrees C after treatment of
      erythrocytes with PEG-1500 under similar conditions, leads to additional
      inhibition of enzyme activity. The identified changes in Ca2+-ATPase activity in
      the presence of PEG-1500 are presumably due to the modifying effect of
      cryoprotectant on the membrane structure and even presence of endogenous
      effectors in the medium cannot overcome the restrictions imposed by the modified
      membrane environment on this enzyme functioning.

PMID- 30188623
TI  - KARYOTYPING OF AMOEBA PROTEUS.
AB  - In this paper, the protocol which we have developed to get satisfactory spreads
      of Amoeba proteus mitotic chromosomes is presented, and the process of
      karyotyping this amoeba species is described. This protocol allows obtaining of
      extended chromosomic with repeatable chromomeres pattern in individual
      chromosomes. We have shown that metaphase in "B"-strain amoebae (one of the type
      strains of A. proteus in the Amoebae Strains Collection at the Institute of
      Cytology) contains 27 chromosome pairs with homologous chromomeric pattern. It is
      ascertained that chromomeric pattern is chromosome-specific feature. The bank of
      images of DAPI- and YoYo1-banded individual metaphase chromosomes of "B"-strain
      of A. proteus is presented.

PMID- 30188624
TI  - THE ANALYSIS OF LGI1 GENE EPIGENETIC ALTERATIONS BY MEANS OF POSTTRANSLATIONAL H3
      HISTONE MODIFICATIONS IN MALIGNANT GLIOMAS.
AB  - Although there is a progress in understanding the causes and consequences of
      genetic and epigenetic changes in glioma malignant transformation, many details
      remain obscure and need further investigation. It is known that process of
      malignant transformation of gliomas is accompanied by gradual loss of LGI1 gene
      expression. However, genetic defects causing LGI1 inactivation have not been
      revealed. In this paper, we have analyzed the LGI1 gene expression in primary
      cultures of malignant gliomas, and compared these data with epigenetic indicators
      of transcriptional activity - posttranslational H3 histone modifications. We have
      show the presence of an epigenetic marker of gene repression H3K9me3 near the
      site of LGI1 transcription initiation in most (5 from 6) studied gliomas. There
      was not LGI1 expression in these gliomas. Only one glioma showed LGI1 expression,
      and in this glioma there was no association of LGI1gene with H3K9me3
      modification. Thus, we are the first to show a correlation between LGI1 gene
      expression and the epigenetic indicator H3K9met3 in malignant gliomas. Marker of
      actively transcribed chromatin I3K4an have not been found in this area of the
      genome. The data obtained strongly suggest the possibility of gene LGL1
      inactivation by epigenetic mechanism: modified "histone code".

PMID- 30188625
TI  - ISOLATION AND CHARACTERIZATION OF CARDIAC PROGENITOR CELLS OBTAINING FROM
      MYOCARDIAL RIGHT ATRIAL APPENDAGE TISSUE.
AB  - Resident stem cells of the heart are denoted as heterogeneous population of
      immature cells, which reside in the myocardium and characterized by their ability
      to self-renewal and are multipotent differentiation capacity into cardiomyocyte
      like and vascular like cells. CSCs were originally isolated directly by long
      enzymatic digestion of heart tissue and selection using stem cell markers.
      However, long exposure to enzymatic digestion and small myocardial sample size
      can affect the possibility of obtaining a significant amount of viable cells. To
      avoid these problems, we developed a method consisting of growing of the CPC in
      explant culture and subsequent immunomagnetic selection.

PMID- 30188626
TI  - CHARACTERISTICS OF A172 AND T98G CELL LINES.
AB  - During continuous cultivation cell lines can lose a number of innate
      characteristics or acquire new ones. In this work we compared growth and
      phenotypic characteristics of human glioblastoma A172 and O98G lines from cell
      culture collection of Research Institute of Influenza of Ministry of Health of
      Russian Federation (St. Petersburg). The activity of genes encoding intracellular
      proteins that determine cell lines belonging to mesenchymal type, as well as
      several growth factor genes and extracellular matrix genes were estimated. Cell
      lines A172 and T98G varied in morphology and surface markers expression. A172
      cells were characterized by higher expression of mesenchymal markers CD90, CD105,
      fibroblast activation protein, and tenascin C. Both cell lines showed high level
      of a2 smooth muscle actin expression. The obtained data indicating high activity
      of genes encoding major inductors of angiogenesis (VEGF, FGF2 (b), TGFb1) and
      thrombospondin-1 in foregoing cell lines are in agreement with published data.
      Reduction of fetal serum in culture medium from 10 to 5 % in both cell lines
      resulted in the increase of proportion of cells with surface antigens CD73 and
      CD105. Both A172 and T98G cell lines sustain the main features of glioblastomas
      and therefore can serve as research objects in investigation of this kind of
      neoplasms.

PMID- 30188627
TI  - Rivaroxaban for Stroke Prevention after Embolic Stroke of Undetermined Source.

PMID- 30188628
TI  - Rivaroxaban for Stroke Prevention after Embolic Stroke of Undetermined Source.

PMID- 30188630
TI  - Rivaroxaban for Stroke Prevention after Embolic Stroke of Undetermined Source.

PMID- 30188629
TI  - NFLUENCE OF MAST CELLS ON REPARATIVE REGENERATION OF TISSUES WITH DIFFERENT
      DEGREE OF IMMUNOLOGICAL PRIVILEGES.
AB  - It is assumed that tissues with different degree of imminological privileges have
      a number of distinctions in the processes of reparation. This may be associated
      with mast cells, which are found in all body tissues of an organism, secrete a
      wide range of biologically active substances and are important in the regulation
      of repair processes. This paper present the results of investigations of
      morphometric parameners and functional activity of mast cells in tissues with
      varying degrees of immune privilege (skin, testis). It has been shown that
      migration of must cells in the skin is observed early after the injury and
      followed by a slow increase of synthetic activity and index of degranulation of
      mastocytes within 30 days. Index of degranulation of mast cells in the testes
      increased immediately after the injury in the absence of their pronounced
      migration. Stabilizing membranes of mast cells using the drug ketotifen led to
      inhibition of the repair of the skin, which was manifested itself in the absence
      of increasing the thickness of dermis, epidermis, the number of fibroblasts and
      collagen fibers, and also in slowing down the formation of scar. At the same
      time, the inactivation of mast cells promoted reparative regeneration of testes
      as was indicated by increase in the number of normal spermatogonia which are
      proliferative pool for all subsequent stages of spermatogenesis, and by
      considerable decrease in the number of non-functioning tubules. Thus, the number
      and the functional sate of the mast cells have an impact on the course of
      reparative processes in tissues with varying degrees of immune privileges.

PMID- 30188631
TI  - TIGHT JUNCTIONS PROTEINS IN CEREBRAL ENDOTHELIAL CELLS DURING EARLY POSTNATAL
      DEVELOPMENT.
AB  - Formation and functional plasticity of the blood-brain barrier is associated with
      the molecular events that occur in the brain neurovascular unit in the embryonic
      and early postnatal development. To study the characteristics of barriergenesis
      under physiological conditions, as well as recovering from perinatal hypoxia and
      early life stress, we examined the expression of proteins of cerebral endothelial
      tight junctions (JAM, ZO1, CLDN5) in rats aged 7, 28 and 70 days of postnatal
      development (P7-P70). Under physiological conditions, we have found that the
      number of endothelial cells expressing JAM, ZO1, CLDN5 slightly increases in the
      cortex, hippocampus and amygdala of the brain in the period from P7 to P70.
      Perinatal hypoxia significantly increased the number of cells expressing proteins
      of tight junction proteins (JAM, CLDN5) up to the age P28-P70, whereas the number
      of cells expressing ZO1 was reduced in the same period of time. Early life stress
      led to an imbalance between the number of cells expressing ZO1 proteins and that
      expressing tight junctions proteins, but these changes were in opposite direction
      to that observed in perinatal hypoxia

PMID- 30188632
TI  - Incidence of Lung Cancer among Young Women.

PMID- 30188633
TI  - Incidence of Lung Cancer among Young Women.

PMID- 30188634
TI  - EEA1 CARRYING VESICLES ARE NOT AUTOPHAGOSOMES IN SERUM-DEPRIVED HeLa CELLS.
AB  - According to current model, stimulation of EGF-receptor endocytosis results in
      recruitment onto early endosomes cytosolic tether protein EEA1 necessary for
      their further fusions. However, EEA1-positive vesicles are found in the cells not
      treated with growth factor, that were incubated in serum-free conditions. It is
      known also that prolonged serum deprivation induces autophagosomes formation, the
      process possibly involving endocytic compartments. To check whether EEA1-positive
      vesicles seen in serum-deprived HeLa cells are autophagosomes, we here evaluated
      colocalization of EEA1 and autophagosome marker LC3 and studied dynamics of the
      EEA1- and LC3-vesicles' number and size during 12-36 h cell cultivation in serum
      free medium. It was found that the number of autophagosomes per cell is
      significantly less than the number of EEA1-vesicles. We show that serum
      starvation results in increase of only mean autophagosomes' size, while the
      number and size of EEA1-vesicles did not changed. Colocalization of EEA1 and LC3
      in serum-free cells was very low during first 12-18 h of starvation and increased
      insignificantly only by 36 h. Biosynthetic pathway inhibition by Golgi apparatus
      disruption by brefeldin A, decreased the number and increased the size of EEA1
      vesicles. LC3-vesicles also demonstrated an increase of mean size and growth of
      colocalization with EEA1. Thus, we conclude that the majority of EEA1-vesicles in
      serum-starved cells are not autophagosomes. More pronounced effect of brefeldin A
      indicates that blockade of biosynthetic pathway is more strong stress factor
      comparing to serum deprivation in HeLa cells. This also suggests that this
      pathway is involved in EEA1-vesicles biogenesis.

PMID- 30188636
TI  - NCREASING OF THE FLUIDITY OF MODEL LIPID MEMBRANES UNDER THE INFLUENCE OF LOCAL
      ANESTHETICS.
AB  - We have studied the effect of local anesthetics on the permeability of
      phospholipid liposomes of various composition to calcein. We have tested amides
      (lidocaine, prilocaine, mepivacaine and bupivacaine) and ester anesthetics
      (benzocaine, procaine and tetracaine). The permeability of large unilamellar
      liposomes to calcein has been determined by measuring the relative fluorescence
      intensity of calcein released from the phospholipid vesicles. We have shown that
      all tested amide anesthetics have little of feet on the leakage of calcein from
      dioleoylphosphocholine (DOPC) liposomes. The most effective amide was did
      bupivacaine. Substitution in the membranes of 20 mol % DOPC on
      tetraoleoylcardiolipin (TOCL) was did accompanied by increased activity of
      amides. Benzocaine and procaine at concentration up to 100 mM practically did not
      change DOPC liposome permeability. Addition of tetracaine up to concentration of
      2 mM did not affect the permeability of vesicl. Further increas in the anesthetic
      concentration up to 50 mM led to increase in the intensity of calcein
      fluorescence and, at a concentration of 100 mM, a complete engagement of
      fluorescent marker was observed. In the case of vesicles including 20 mol % TOCL,
      the threshold concentration of tetracaine and the concentration that corresponded
      to 100% leakage of calcein were been 7 and 20 mM, respectively. Using confocal
      fluorescence microscopy of giant unilamellar vesicles formed from an equimolar
      mixture of DOPC and tetramyristoylcardiolipin (TMCL), we have shown that
      anesthetics destroy solid ordered domains, and this ability increases in the
      order: procaine d mepivacaine < bupivacaine n tetracaine. The revealed
      differences in the effect of local anesthetics might be caused by different depth
      of immersion of the anesthetics into the membrane.

PMID- 30188635
TI  - Incidence of Lung Cancer among Young Women.

PMID- 30188637
TI  - EXTRA-CELLULAR DNA FOR THE UNSOLVED EVOLUTIONAL PROBLEMS.
AB  - The genome assembly and new sequencing methods shed light on extra-cellular DNA
      (ecDNA) content and uptake. The recent data are described. The asymmetry in
      repetitive sequences distribution in ecDNA are shown: 1) significant enrichment
      in pericentromeric tandem repeats (TR), but decrease of centromeric alpha
      satellite; 2) enrichment in Alu (SINE) but decrease of LINEs. In the genomes, Alu
      repeats (SINE) are located mostly to the gene-rich regions, while LINEs enrich
      facultative heterochromatin as evidenced by bioinformatics and cytological data
      (FISH). Human shows a greater fraction of tissue-specific genes and a greater
      ratio of the total expression of tissue-specific genes to housekeeping genes in
      each tissue studied. A higher level of evolutionary cell differentiation
      (specialization) in human correlates with the substitution of 4 mouse SINEs with
      Alu (SINE) repeat. Sperm-mediated gene transfer became the ordinary methods of
      the veterinary. The overall substitution of ecDNA SINEs in the whole genome by
      recombination is possible due to Alu element and mouse B1 (SINE) sequence
      similarity. The orthologous genes are not altered initially but chromatin
      landscape change lifts up the transcription and provides the evolutionary
      advantage for the newly born species. So, the scheme suggested may remove two of
      the contradictions of the Modern evolutionary synthesis theory: 1) gene mutations
      are not necessary for the progressive evolution but repetitive elements
      substitution; 2) ancient mammalians could have litters with the number of
      offspring altered by ecDNA and inbred mating was possible for the descendant
      altered.

PMID- 30188638
TI  - THE STRUCTURE OF DNA CHROMOCENTRES IN MOUSE IN SILICO AND IN SITU. LINE AND ERV
      FRAGMENTS ARE AN OBLIGATORY COMPONENTS OF DNA CHROMOCENTRES BESIDES TANDEM
      REPEATS.
AB  - Constitutive heterochromatin in higher eukaryotes is located in the primary
      chromosomal strangulation (centromeres and pericentromeres) and subtelomeric
      regions of chromosomes. In house mouse constitutive chromatin formes structures
      in the nuclei of cells, brightly colored with DAPI. It is known that the
      constitutive heterochromatin is enriched with large tandem repeats, however, its
      exact composition is unknown. In this paper chromocenters were studied using
      several approaches: cloning and sequencing by Sanger, as well as by high
      throughput sequencing. We have shown that DNA components of chromocenters and
      constitutive chromatin are full-length endogenous retroviruses (ERV) and a 2 kbp
      fragment of the 3R-end of the LINE.

PMID- 30188639
TI  - E-Cigarettes, Incentives, and Drugs for Smoking Cessation.

PMID- 30188641
TI  - E-Cigarettes, Incentives, and Drugs for Smoking Cessation.

PMID- 30188640
TI  - HE ROLE OF REPETITIVE SEQUENCES IN THE EVOLUTION OF SEX CHROMOSOMES IN BIRDS.
AB  - In this paper, we analyzed the distribution and the transcriptional activity of
      different repetitive elements in the sex chromosomes of chicken at the lampbrush
      stage. Based on these results, we suggest participation of interspersed repeats
      in the maintenance evolutionarily significant level of variability of
      heteromorphic sex chromosomes in birds. Analysis of the organization
      peculiarities of chicken sex chromosome W specific repeats allowed us to
      hypothesize that the accumulation of tandem repeats enriched with homopurine
      tracks is significant for the evolution of sex chromosomes.

PMID- 30188642
TI  - GENES CODING RIBOSOMAL PROTEIN RPL11 AND 5,8S RIBOSOMAL RNA IN SPECIES OF GENUS
      CHIRONOMUS: NUCLEOTIDE VARIABILITY, DIVERGENCE AND CHROMOSOMAL LOCATION.
AB  - Ribosomes of eukaryotic cells contain four rRNA's (28S, 18S, 5,8S and 5S) and
      about 80 ribosomal proteins (RP). Whereas the patterns of evolution and
      chromosomal location of rRNA genes are studied rather extensively in many
      taxonomic groups, there is only scarce information about evolution of genes
      coding ribosomal proteins. To obtain more information about evolution of
      ribosomal protein genes, the study of the nucleotide sequences and chromosomal
      location of rp111 gene was carried out in 12 species of the genus Chironomus.
      Characteristics of intra- and interspecific variability of this gene have been
      obtained and a high percenatage of identity has been shown between nucleotide
      sequences of different species from the Chironomus. FISH analysis has shown that
      ribosomal protein gene rp111 is located in a single site (region 25f), near
      centromere of the arm B. No variations in the number of sites and chromosomal
      position of the gene were observed in the karyotypes of the studied chironomid
      species indicating the evolutionary conservation of the chromosomal region where
      rp111 is located. We have established that the number and location of rp111 gene
      in chromosomal karyotypes of studied chironomid species do not coincide with the
      number and positions of 5,8S rRNA gene. The data obtained allow to conclude that
      the evolution of nucleotide sequences and chromosomal location of rp111 and 5,8S
      rRNA genes in genomes of Chironomus species occurred independently.

PMID- 30188643
TI  - DIVERSITY OF SEX DETERMINING MECHANISMS IN RAY-FINNED FISHES (ACTINOPTERYGII).
AB  - Ray-finned fishes (Actinopterygii) is a very diverse and numerous clade of
      vertebrates. Besides the diversity of ecological niches and morphology, species
      of this clade have substantial differences in mechanisms of sex determination.
      Unfortunately, our modern knowledge about sex determining mechanisms is limited
      to a small number of species. Even from the modest number of published works on
      this topic it is obvious that evolution of sex determining system in ray-finned
      fishes is very plastic: in some closely related species sex systems can be
      significantly different, there are taxa with quite conservative systems, and the
      same genomic loci may play sex determination role independently in various
      groups. Such diversity allows considering ray-finned fishes to be used as a
      convenient model taxon for researching emergence and development of different sex
      determining systems.

PMID- 30188644
TI  - A POSSIBLE CYTOGENETIC ANALOGY TO GENOMIC "SPECIATION ISLANDS" AS REVEALED BY
      CHROMOSOME STUDY OF A NATURAL HYBRID VOLE.
AB  - Chromosome analysis in mammals over the last half century has largely focused on
      species identification. A growing number of hybrid zones of karyotypically
      differentiated cryptic taxa have been described. A good example is provided by
      two karyoforms of the 46-chromosome common vole (long known as "arvalis" and
      "obscurus") that make contact longitudinally from the north to the south of
      European Russia. The hybrid F1 karyotype displays genomic markers which
      distinguish arvalis and obscurus and which are cytogenetically detectable as
      minor variants. The apparent insignificance of the genomic region of
      heterozygosity associated with these markers perhaps does not prevent hybrid
      chromosome pair formation at meiosis but may reflect a site resistant to gene
      flow. A cytogenetic analogy with so-called "speciation islands", based, for
      example, on the study of the corvine hybrid zone and represented by a small
      number of limited genomic sites (occupying less than 1 % of the genome) (Poelstra
      et al., 2014), may be relevant.

PMID- 30188660
TI  - [STEM CELL NICHES AND REGENERATIVE MEDICINE].
AB  - The review is devoted to modern state of science in the area of stem cell niches.
      Fundamental characteristics of niche including extracellular matrix are
      considered. Key principles of niche functioning are demonstrated by the example
      of hematopoietic and epithelial cells. Special section discusses the use of stem
      cells and their microenvironment in regenerative medicine.

PMID- 30188661
TI  - [THE ROLE OF AlphA1-ADRENORECEPRORS FOR ACTIVITY OF THE HEART IN HUMANS AND
      ANIMALS. PART 2].
AB  - The second part of the review analyzes literature data that proves the importance
      of the role of alpha1-adrenergic receptor (AR) in the implementation of the
      trophic effects on the myocardium by the sympathetic nervous system and
      adrenaline as adrenal hormones. This function is described as follows: the
      activation of alpha1-AR induces a physiological cardiac hypertrophy and causes
      cardioprotective effect which is manifested in inhibition of cardiomyocyte death
      caused by various kinds of stress. The review gives information on the mechanisms
      which form the basis of hypertrophy and cardioprotective effect, as well as the
      role of alpha1-AR in maintaining the heart pump function in heart failure and
      cardiac adaptation to ischemia. In particular, it reports on the involvement of
      phospholipase C, protein kinase C, protein kinase D, histone deacetylase,
      phosphatidylinositol 3-kinase (PI3-K), PI3-K-dependent protein kinase, protein
      kinase B (Akt), MAP-kinases and several transcription factors. The details of the
      application prospects of alpha1-AR agonists in the treatment of heart failure are
      discussed.

PMID- 30188662
TI  - [COMPARISON OF THE BEHAVIOR OF RHESUS MONKEY MALES IN INDIVIDUAL AND GROUP
      KEEPING CONDITIONS: AGGRESSIVENESS AND ANXIETY].

PMID- 30188663
TI  - [THE P-GLYCOPROTEIN EXPRESSION IN BLOOD-BRAIN BARRIER AND ITS CORRELATION WITH
      REDOX-STATUS IN ISCHEMIA AND ISCHEMIA-REPERFUSION].

PMID- 30188665
TI  - [MECHANISMS OF THE PULMONARY CIRCULATORY CHANGES FOLLOWING EXPERIMENTAL INFERIOR
      VENA CAVA STENOSIS].

PMID- 30188664
TI  - [ORGANIZED STRUCTURE OF VENTRICULAR FIBRILLATION IN CANINE HEART].
AB  - The first 7 minutes of ventricular fibrillation (VF) are characterized by an
      organized electrical activity that confirmed by the dominant frequency structure
      of oscillations. The first minute of ventricular fibrillation is characterized by
      lowering of the frequency of dominating oscillations with the transition from the
      domination of the medium frequency oscillations (8-12 Hz) to the domination of
      the low frequency oscillations (4-7 Hz). During 2-7 minutes, ventricular
      fibrillation is characterized by reducing of the domination of the low frequency
      oscillation and with the transition to the domination of the low and medium
      frequency oscillations. Ventricular fibrillation acquires the nondominant
      character after the 7-th minute of VF. Organized structure of ventricular
      fibrillation is resistant to ischemia: organized structure have persisted under
      the influence of 7 minutes of ischemia on myocardium during fibrillation.

PMID- 30188666
TI  - [SYNCHRONIZATION OF CHARACTERISTICS OF ACTION POTENTIALS IN RHYTHMOGENIC AREAS OF
      MIOMETRIUM UNDER THE INFLUENCE OF OXYTOCIN].

PMID- 30188667
TI  - [MECHANISMS OF PROULCEROGENIC EFFECT OF CORTISOL AT PHARMACOLOGICAL DOSE ON THE
      GASTRIC MUCOSA].
AB  - In this study, we investigated the mechanisms of proulcerogenic effect of
      Cortisol at pharmacological dose on the gastric mucosa in rats. Cortisol (300
      mg/kg, ip, single) was administered 1, 3, 5, 7 and 30 days before ulcerogenic
      stimulus (indomethacin, 35 mg/kg, sc). The gastric mucosa integrity, blood
      corticosterone, glucose levels, the body weight and the thymus and spleen weight
      were tested 4 h after indomethacin or at appropriate day after cortisol treatment
      (in rats without indomethacin). Cortisol treatment resulted in an increase in
      blood glucose levels with a maximum at day 3, decrease in the body weight and
      weight of the thymus and the spleen. A deficiency of glucocorticoids in the blood
      and an increase in indomethacin-induced gastric injury were observed 7 days after
      the cortisol pretreatment. At the same time all parameters did not differ from
      controls 30 days after cortisol pretreatment. The results suggest that cortisol
      at a pharmacological dose may cause proulcerogenic action on the gastric mucosa
      through a long-lasting maintenance of blood glucose levels accompanied by the
      signs of catabolic effect and through a deficiency of glucocorticoid production.

PMID- 30188668
TI  - [TESTICULAR FUNCTION AND LIPID METABOLISM IN MALE MICE WITH HEREDITARY
      PREDISPOSITION TO OBESITY].
AB  - Parameters of spermatogenesis, androgen status and lipid metabolism (amount of
      abdominal fat, cholesterol and triglycerides plasma levels) in male mice with the
      mutation yellow at the locus agouti (Ay mice), which results in obesity after
      puberty were studied. Their lean littermate's mice of standard C57BL/6J strain
      genotype (a/a mice) were used as a control. At the age of 15 and 30 weeks the
      body weight, triglyceride levels, and at the age of 30 weeks - abdominal fat mass
      in Ay males were higher than that of a/a males. These data confirm the
      development of obesity and disturbance of lipid metabolism in Ay males. There
      were no changes in the number of sperm in the caudal epididymis, the proportion
      of mobile and morphologically abnormal sperm, the concentration of testosterone
      and its content in the testes in Ay mice at the reproductively active period (age
      15 and 30 weeks). It is assumed that the ectopic expression of agouti protein in
      Ay males may be involved in the protection of the testicular function from the
      negative impact of obesity.

PMID- 30188669
TI  - [ADAPTIVE REMODELLING OF BONE TISSUE IN TOTAL HIP REPLACEMENT].
AB  - Instrumental and laboratory monitoring of bone tissue adaptive remodeling
      processes after total hip replacement conducted for primary osteoarthrosis
      patients (32 males and 48 females) (coxarthrosis stage III, functional
      insufficiency stages II and III) with long-lasting joint damage, significant pain
      syndrome and osteodeficit, indicated osteodeficit intensification compared to the
      baseline in the implant surrounding areas. These patients showed an increasing
      cytokine imbalance in the blood serum postsurgically with the primary activation
      of proinflammatory (osteoresorbing) element and secondary activation of anti
      inflammatory element. Structural and functional characteristics of bone tissue in
      the area adjacent to the implant and cytokine balance indexes in the blood serum
      did not return to the baseline even 12-15 months postsurgically.

PMID- 30188670
TI  - [TRANSMASTOIDAL GALVANIC VESTIBULAR STIMULATION AS A TOOL FOR HUMAN MOTOR
      FUNCTION CORRECTION].

PMID- 30188671
TI  - [IMPAIRMENTS OF GLUTAMATERGIC TRANSMISSION IN THE BASOLATERAL NUCLEUS OF THE
      AMYGDALA IN THE DEVELOPMENT OF ALCOHOL DEPENDENCE].
AB  - In this review for the first time systematized literature data about the
      impairments of glutamatergic transmission in the basolateral nucleus of the
      Amygdala which leading to increased levels of anxiety. It is known that increased
      anxiety is seen as a main motivating factor of desire for alcohol, thus involved
      in the manifestation of alcohol dependence. Reviewed structural-functional
      alterations in ionotropic and metabotropic glutamate receptors in acute, chronic
      ethanol exposure and withdrawal. Presents the data on the role of glutamate
      transporters in the pathogenesis of alcoholism.

PMID- 30188672
TI  - [PHENOMENON OF REMOTE PRECONDITIONING THE HEART AND ITS MAIN MANIFESTATIONS].
AB  - Remote ischemic preconditioning prevents reperfusion cardiomyocyte apoptosis and
      has the infarct-limiting effect which is maintained in the experiments on the
      isolated perfused heart. Remote preconditioning promotes to recovery the
      contractility of the heart during reperfusion, but did not affect the incidence
      of occlusion and reperfusion of ventricular arrhythmias. Remote preconditioning
      has a mild anti-inflammatory effect. Presented article is a review and formulated
      conclusions based on the published literature data.

PMID- 30188673
TI  - [THE INTEGRATIVE LEVEL OF THE HIERARCHICAL SYSTEM OF SPATIAL ORIENTATION OF
      ANIMALS].
AB  - The purpose of this review is to analyze the current knowledge about the higher,
      integrative level of the physiological system of orientation of animals in space.
      The significance of the study of this level caused by the fact that its
      disruption can cause deterioration of the capacity for spatial orientation
      (spatial agnosia) which is an important sign of some diseases of the brain, and
      in particular Alzheimer's disease. In recent decades, the main functional
      components of integration of information on space position of animals were
      discovered. The significance of these discoveries was reflected in a number of
      prestigious awards and honors, including the Nobel Prize in Physiology or
      Medicine for 2014.

PMID- 30188674
TI  - [PROBLEM OF END EFFECTOR OF ISCHEMIC PRECONDITIONING OF THE HEART].
AB  - An analysis of the literature data performed by the authors shows that the main
      contenders for the role of the end effector of ischemic preconditioning of the
      heart are: (1) MPT pore (2) nexuses (3) cytoskeleton. Thus, almost all of the
      known intracellular molecular cascades eventually converge on MPT pore, on the
      components of the cytoskeleton and nexuses.

PMID- 30188675
TI  - [BLOCKING SENSORIMOTOR DISORDERS IN STRIATIC DOPAMINERGIC DEFICIENT MICE BY THE
      EXTRACTS OF "REMEDY BEETLE" ALPHITOBIUS DIAPERINUS].
AB  - Five groups of C57Bl/6JSto mice (groups 1-5) were tested on a vertical pole 2
      weeks since subcutaneous administration of proneurotoxin MPTP (40 mg per kg b.
      w.) to groups 2-5. Group 1 served as control. It is known that this MPTP dosage
      forms within 2 weeks sensorimotor disturbances similar to the initial stage of
      Parkinson's disease. One week before MPTP injection and during all the period
      after it (2 weeks) animals of groups 3-5 got one of the three extracts of biomass
      homogenate of the "remedy beetle" Alphitobius diaperinus as an additive to their
      food (8 g per 1 kg of food). The extracts were as follows: water (N 1), water
      methanol (N 2) and water-methanol one after solid-phase extraction (N 3). All
      extracts were immobilized on a phytocarrier. Animals of groups 1 & 2 used
      ordinary food. Sensorimotor disturbances which could be clearly seen in the 2nd
      group of mice (MPTP) were absent in group 1 (control) as well as groups 3-5 which
      received an "antidote" with their food as one of the extracts of homogenate of
      the beetle biomass. The extract N 3 demonstrated maximal efficiency of all.

PMID- 30188676
TI  - [ADRENERGIC AND IMIDAZOLINE MECHANISMS OF CIRCULATION CENTRAL REGULATION IN RATS
      OF DIFFERENT LINES].
AB  - The purpose of this work was a comparative analysis of the brain adrenergic and
      imidazoline receptors activation effects in laboratory rats with normal and
      elevated activity of the sympathetic nervous system. The experiments were carried
      out on male rats of Wistar and Wistar-Kyoto lines and spontaneously hypertensive
      (SHR) line. In freely moving rats the mean arterial pressure, heart beat-to-beat
      interval and cardiochronotropic component of baroreceptor reflex were recorded
      and analyzed at rest and emotional stress, caused by a conditioned signal.
      Agonist of imidazoline and adrenergic receptor clonidine, a primary agonist of
      imidazoline receptor moxonidine, selective alpha 2-adrenoreceptor blocker
      yohimbine and blocker of imidazoline and alpha - adrenergic receptor efaroksan
      were used for neurochemical analysis of adrenergic and imidazoline systems role
      in mechanisms of regulation of blood circulation. Our data have shown, that if
      adrenergic systems of the brain provide its participation in the long-term
      regulation of blood pressure, stimulation of imidazoline receptors activate the
      central link of baroreceptor reflex arc at the level of the medulla oblongata and
      also strengthening the processes of its suprabulbar modulation, caused by
      emotional stress.

PMID- 30188677
TI  - [THE INFLUENCE OF HISTAMINE ON THE EFFECTOR NEURONS OF INTRAMURAL GANGLIA OF THE
      TRACHEA AND BRONCHI].
AB  - We considered the influence of the neurons of intramural ganglia in the reaction
      of the smooth muscle trachea and bronchi caused by electric field stimulation, by
      the action of histamine. We studied the effect of neurons of intramural ganglia
      in the activity of the smooth muscle trachea and bronchi in the action of low
      doses of histamine (0,1 and 10 MUg/ml), L-NAME and hexamethonium. It was shown
      the blockade of neuronal transmission decreased the contraction of the smooth
      muscles trachea and bronchi by stimulation of the afferent nerve structures. The
      smooth muscle relaxation under the influence of hexamethonium was also reduced.
      Histamine and hexamethonium increased contractile activity and increased the
      amplitude of the relaxation of the trachea and bronchi. The inhibition of NO-
      synthesis did not affect on the contraction, but reduced the relaxation of the
      trachea and bronchi. Histamine and L-NAME enhanced contractile activity, but not
      modified smooth muscle relaxation. Concluded that the neurons of intramural
      ganglia have an inhibitory effect on the smooth muscle of the trachea and bronchi
      and may have a modulating effect on contraction and dilatation of the smooth
      muscles of the airways.

PMID- 30188678
TI  - Aegis of Lithium-Rich Cathode Materials via Heterostructured LiAlF4 Coating for
      High-Performance Lithium-Ion Batteries.
AB  - Lithium-rich oxides have been regarded as one of the most competitive cathode
      materials for next-generation lithium-ion batteries due to their high theoretical
      specific capacity and high discharge voltage. However, they are still far from
      being commercialized due to low rate capability and poor cycling stability. In
      this study, we propose a heterostructured LiAlF4 coating strategy to overcome
      those obstacles. The as-developed lithium-rich cathode material shows outstanding
      performance including a high reversible capacity (246 mA h g-1 at 0.1C),
      excellent rate capability (133 mA h g-1 at 5C), and ultralong cycling stability
      (3000 cycles). Comparing with those of pristine and AlF3-coated lithium-rich
      cathode materials, the enhanced performances can be attributed to the
      introduction of the lithium-ion-conductive nanolayer and the generation of
      nonbonding O n- species in the active material lattice, which enable rapid and
      effective lithium ion transport and diffusion. Our work provides a new strategy
      to develop high-performance lithium-rich cathode materials for high-energy
      density lithium-ion batteries.

PMID- 30188679
TI  - Orthorhombic NiSe2 Nanocrystals on Si Nanowires for Efficient
      Photoelectrochemical Water Splitting.
AB  - Photocatalytic water splitting is a vital technology for clean renewable energy.
      Despite enormous progress, the search for earth-abundant photocatalysts with long
      term stability and high catalytic activity is still an important issue. We report
      three possible polymorphs of nickel selenide (orthorhombic phase NiSe2, cubic
      phase NiSe2, and hexagonal phase NiSe) as bifunctional catalysts for water
      splitting photoelectrochemical (PEC) cells. Photocathodes or photoanodes were
      fabricated by depositing the nickel selenide nanocrystals (NCs) onto p- or n-type
      Si nanowire arrays. Detailed structural analysis reveals that compared to the
      other two types, the orthorhombic NiSe2 NCs are more metallic and form less
      surface oxides. As a result, the orthorhombic NiSe2 NCs significantly enhanced
      the performance of water-splitting PEC cells by increasing the photocurrents and
      shifting the onset potentials. The high photocurrent is ascribed to the excellent
      catalytic activity toward water splitting, resulting in a low charge-transfer
      resistance. The onset potential shift can be determined by the shift of the flat
      band potential. A large band bending occurs at the electrolyte interface, so that
      photoelectrons or photoholes are efficiently generated to accelerate the
      photocatalytic reaction at the active sites of orthorhombic NiSe2. The remarkable
      bifunctional photocatalytic activity of orthorhombic NiSe2 promises efficient PEC
      water splitting.

PMID- 30188680
TI  - Zwitterionic Polymer Modified Porous Carbon for High-Performance and Antifouling
      Capacitive Desalination.
AB  - Capacitive deionization (CDI) is an emerging technology for effective brackish
      water desalination to address fresh water scarcity. It is of great interest due
      to its high energy efficiency, environmental friendliness, and low-cost operation
      compared with traditional desalination technologies. However, electrode fouling,
      caused by dissolved organic matter and resulting in reduction of electrode
      electrosorption capacity and device lifespan, is an impediment to practical
      application of CDI. Herein, we report a novel salty water desalination electrode
      with excellent antifouling properties. The antifouling electrode is prepared by
      coating zwitterionic polymer brushes, i.e., poly(sulfobetaine methacrylate)
      (SBMA), on porous carbon (PC) via surface-initiated atom transfer radical
      polymerization. The successful coating of zwitterionic polymer on PC surface is
      confirmed by transmission electron microscopy, scanning electron microscopy, X
      ray photoelectron spectroscopy, thermogravimetric analysis, and other
      characterizations. Coating with polySBMA did not affect the electrosorption
      capacity of PC electrodes and imparted antifouling properties (versus fouling by
      model foulant bovine serum albumin) during long-term salt removal tests (100
      desalination/regeneration cycles). This is an important step toward practical
      application of capacitive deionization technology for brackish water
      desalination.

PMID- 30188681
TI  - Amphiprotic Side-Chain Functionalization Constructing Highly Proton/Vanadium
      Selective Transport Channels for High-Performance Membranes in Vanadium Redox
      Flow Batteries.
AB  - A novel amphiprotic side-chain-functionalized membrane was for the first time
      designed for vanadium redox flow battery (VFB). Different from frequently used
      blending amphiprotic membranes, the one proposed here is allowed to possess high
      anion-exchange capacity (IECa) without sacrificing the cation-exchange capacity
      (IECc) because both IECa and IECc increased with the grafting degree of side
      chains. Having a high IECa, the membrane prepared here exhibits an ultralow
      vanadium permeability (<10-8 cm2 s-1), which leads to very high Coulombic
      efficiencies (97-98% at 40-200 mA cm-2) of VFB and good cell self-discharge
      durability. Moreover, the high IECc contributes to a decent ionic conductivity
      (area resistance: 0.5 Omega cm-2), which ensures a high-voltage efficiency of the
      cell. On the basis of these good properties, the VFB single cell with this
      membrane achieves a high energy efficiency (e.g., 77.4% at 200 mA cm-2) that is
      higher than those of Nafion 212 and other reported amphiprotic membranes. These
      results indicate that the approach proposed here is an ideal option to prepare
      amphiprotic membranes for VFBs with high efficiency and good durability.

PMID- 30188682
TI  - Uncovering the Formation of Color Gradients for Glucose Colorimetric Assays on
      Microfluidic Paper-Based Analytical Devices by Mass Spectrometry Imaging.
AB  - This study describes the use of mass spectrometry imaging with matrix-assisted
      laser desorption/ionization (MALDI) and desorption electrospray ionization (DESI)
      to understand the color gradient generation commonly seen in microfluidic paper
      based analytical devices (MUPADs). The formation of color gradients significantly
      impacts assay sensitivity and reproducibility with MUPADs but the mechanism for
      formation is poorly understood. The glucose enzymatic assay using potassium
      iodide (KI) as a chromogenic agent was selected to investigate the color gradient
      generated across a detection spot. Colorimetric measurements revealed that the
      relative standard deviation for the recorded pixel intensities ranged between 34
      and 40%, compromising the analytical reliability. While a variety of hypotheses
      have been generated to explain this phenomenon, few studies have attempted to
      elucidate the mechanisms associated with its formation. Mass spectrometry imaging
      using MALDI and DESI was applied to understand the nonuniform color distribution
      on the detection zone. MALDI experiments were first explored to monitor the
      spatial distribution of the glucose oxidase and horseradish peroxidase mixture,
      before and after lateral flow assay with and without KI. MALDI(+)-TOF data
      revealed uniform enzyme distribution on the detection spots. On the other hand,
      after the complete assay DESI(-) measurements revealed a heterogeneous shape
      indicating the presence of iodide and triiodide ions at the zone edge. The
      reaction product (I3-) is transported by lateral flow toward the zone edge,
      generating the color gradient. Mass spectrometry imaging has been used for the
      first time to prove that color gradient forms as result of the mobility small
      molecules and not the enzyme distribution on MUPAD surface.

PMID- 30188683
TI  - Combining Desorption Electrospray Ionization Mass Spectrometry Imaging and
      Machine Learning for Molecular Recognition of Myocardial Infarction.
AB  - Lipid profile changes in heart muscle have been previously linked to cardiac
      ischemia and myocardial infarction, but the spatial distribution of lipids and
      metabolites in ischemic heart remains to be fully investigated. We performed
      desorption electrospray ionization mass spectrometry imaging of hearts from in
      vivo myocardial infarction mouse models. In these mice, myocardial ischemia was
      induced by blood supply restriction via a permanent ligation of left anterior
      descending coronary artery. We showed that applying the machine learning
      algorithm of gradient boosting tree ensemble to the ambient mass spectrometry
      imaging data allows us to distinguish segments of infarcted myocardium from
      normally perfused hearts on a pixel by pixel basis. The machine learning
      algorithm selected 62 molecular ion peaks important for classification of each
      200 MUm-diameter pixel of the cardiac tissue map as normally perfused or
      ischemic. This approach achieved very high average accuracy (97.4%), recall
      (95.8%), and precision (96.8%) at a spatial resolution of ~200 MUm. In addition,
      we determined the chemical identity of 27 species, mostly small metabolites and
      lipids, selected by the algorithm as the most significant for cardiac pathology
      classification. This molecular signature of myocardial infarction may provide new
      mechanistic insights into cardiac ischemia, assist with infarct size assessment,
      and point toward novel therapeutic interventions.

PMID- 30188684
TI  - In2O3 Nanowire Field-Effect Transistors with Sub-60 mV/dec Subthreshold Swing
      Stemming from Negative Capacitance and Their Logic Applications.
AB  - Heat dissipation is a key issue for scaling metal-oxide-semiconductor field
      effect transistors (MOSFETs). The Boltzmann distribution of electrons imposes a
      physical limit on the subthreshold swing (SS), which impedes both the reduction
      of the switching energy and the further increase of the device density. The
      negative capacitance effect is proposed to rescue MOSFETs from this phenomenon
      called "Boltzmann tyranny". Herein, we report In2O3 nanowire (NW) transistors
      with SS values in the sub-60 mV/dec region, which utilize the ferroelectric P(VDF
      TrFE) as the dielectric layer. An ultralow SS down to ~10 mV/dec is observed and
      spans over 5 orders of magnitude in the drain current. Meanwhile, a high on/off
      ratio of more than 108 and a transconductance ( gm) of 2.3 MUS are obtained
      simultaneously at Vd = 0.1 V. The results can be understood by the "voltage
      amplification" effect induced from the negative capacitance effect. Moreover, the
      steep slope FET-based inverters indicate a high voltage gain of 41.6. In addition
      to the NOR and NAND gates, the Schmitt trigger inverters containing only one
      steep slope FET are demonstrated. This work demonstrates an avenue for low-power
      circuit design with a steep SS.

PMID- 30188685
TI  - Thin Nacre-Biomimetic Coating with Super-Anticorrosion Performance.
AB  - The rigorous organic and inorganic laminated structure of nacre has been
      developed by millions of years of biological evolution against various external
      impacts, including mechanical loadings and chemical attacks. Nacre-biomimetic
      materials have been recognized as an effective strategy to achieve high strength
      and toughness simultaneously. However, the understanding of nacre-like structure
      from the perspective of corrosion protection is still very limited. This work
      investigates the anticorrosion performance of nacre-biomimetic GO/epoxy (NBGE)
      coatings with alternating layers. Potentiodynamic polarization measurements
      indicated that the corrosion rate of steel protected by the NBGE coating with 5
      layers of GO and 6 layers of epoxy (5NBGE) and a total thickness of 17 MUm was 20
      times slower than that of steel under the pure epoxy coating twice as thick in
      3.5 wt % NaCl solution. Electrochemical impedance spectroscopy measurements
      revealed the importance and functions of the GO layers in NBGE coatings. The
      5NBGE coating exhibited better performance than carbon-based nanoparticle/epoxy
      mixed coatings. The superior anticorrosion performance of the NB5G6E coating was
      supported by photographic observations, scanning electron microscopy, energy
      dispersive X-ray spectroscopy, and chloride diffusion measurements. The strong
      cross-linking layer-by-layer structure of NBGE coatings was proved by Fourier
      transform infrared spectroscopy, X-ray photoelectron spectroscopy, and X-ray
      diffraction analyses. The anticorrosion mechanism of the NBGE coatings was
      interpreted by the mitigation of chemical reactions occurring at the steel
      coating interface due to the restricted intrusion of O2, H2O, and Cl- through the
      reduced pores and defects by the intercalated GO layers in the coatings.

PMID- 30188686
TI  - An Efficient Approach for Selective Enrichment of Histone Modification Readers
      Using Self-Assembled Multivalent Photoaffinity Peptide Probes.
AB  - Histone post-translational modifications (HPTMs) provide signaling platforms to
      recruit proteins or protein complexes (e.g., transcription factors, the so-called
      "readers" of the histone code), changing DNA accessibility in the regulation of
      gene expression. Thus, it is an essential task to identify HPTM readers for
      understanding of epigenetic regulation. Herein we designed and prepared a novel
      HPTM probe based on self-assembled multivalent photo-cross-linking technique for
      selective enrichment and identification of HPTM readers. By use of trimethylation
      of histone H3 lysine 4, we showcased that the functionalized HPTM probe was able
      to capture its reader with high enrichment efficiency and remarkable specificity
      even in a complex environment. Notably, this approach was readily applicable for
      exploring crosstalk among multiple HPTMs. Combining the probes with a mass
      spectrometry-based proteomic approach, our approach reached a fairly high
      coverage of known H3K4me3 readers. We further demonstrated that the HPTM probes
      can enrich a new type of HPTM readers and uncovered several novel putative
      binders of crotonylation of histone H3 lysine 9, expanding the repertoire of
      readers for this epigenetic mark. More broadly, our work provides a general
      strategy for rapid and robust interrogating HPTM readers and will be of great
      importance to elucidate epigenetic mechanism in regulating gene activity.

PMID- 30188688
TI  - Complementary Ionization Techniques for the Analysis of Scotch Whisky by High
      Resolution Mass Spectrometry.
AB  - Fourier transform mass spectrometry (FTMS) is widely used to characterize the
      chemical complexity of mixtures, such as natural organic matter (NOM), petroleum,
      and agri-food products (including Scotch whisky). Although electrospray
      ionization (ESI) is by far the most widely used ionization source in these
      studies, other ionization techniques are available and may offer complementary
      information. In a recent study, we found matrix free laser desorption/ionization
      (LDI) to be effective for the analysis of Suwannee river fulvic acid (SRFA), and
      to provide complementary chemical insights. In this study, LDI along with
      atmospheric pressure photoionization (APPI) and atmospheric pressure chemical
      ionization (APCI) were compared to ESI for the analysis of Scotch whisky. High
      mass accuracy (54 ppb, mean) allowed for the assignment of 86% of peaks, with
      3993 unique molecular formulas identified from four representative samples
      analyzed. All four ionization techniques, performed in negative mode, identified
      thousands of formulas. Many were unique to each ionization source, while 699
      formulas were common to all techniques. Ions were identified in both deprotonated
      and radical anion forms. Our study highlights the importance of a multi
      ionization source approach; we recommend that analysis of complex mixtures,
      especially novel ones, should not be limited solely to ESI.

PMID- 30188689
TI  - Nanofibers Regulate Single Bone Marrow Stem Cell Osteogenesis via FAK/RhoA/YAP1
      Pathway.
AB  - Understanding cell-material interactions is a prerequisite for the development of
      bio-inspired materials for tissue regeneration. While nanofibrous biomaterials
      have been widely used in tissue regeneration, the effects of nanofibrous
      architecture on stem cell behaviors are largely ambiguous because the previous
      biomaterial systems used for nanofiber-cell interactions could not exclude the
      interference of cell-cell interactions. In this study, we developed a unique
      micropatterning technology to confine one single stem cell in a microisland of
      the nanofibrous micropatterned matrix; therefore, eliminating any potential
      intercellular communications. The nanofibrous micropatterned matrix, which
      mimicked both the physical architecture and chemical composition of natural
      extracellular matrix, was fabricated by a combination of electrospinning,
      chemical crosslinking, and UV-initiated photolithography. Compared to the non
      nanofibrous architecture, a bone marrow mesenchymal stem cell (BMSC) cultured on
      the nanofibrous microisland exhibited a more in vivo-like morphology, a smaller
      spreading area, less focal adhesion, and fewer stress fibers. The BMSC cultured
      on the nanofibrous microisland also had higher alkaline phosphatase activity,
      indicating nanofibrous architecture promoted BMSC differentiation. A mechanistic
      study reveals that nanofibers regulate single BMSC osteogenesis via the
      FAK/RhoA/YAP1 pathway. The nanofibrous micropatterned matrix developed in this
      study is an excellent platform to promote the fundamental understanding of cell
      matrix interactions, ultimately provide valuable insights for the development of
      novel bio-inspired scaffolds for tissue regeneration.

PMID- 30188687
TI  - Multimodal Chemical Analysis of the Brain by High Mass Resolution Mass
      Spectrometry and Infrared Spectroscopic Imaging.
AB  - The brain functions through chemical interactions between many different cell
      types, including neurons and glia. Acquiring comprehensive information on
      complex, heterogeneous systems requires multiple analytical tools, each of which
      have unique chemical specificity and spatial resolution. Multimodal imaging
      generates complementary chemical information via spatially localized molecular
      maps, ideally from the same sample, but requires method enhancements that span
      from data acquisition to interpretation. We devised a protocol for performing
      matrix-assisted laser desorption/ionization (MALDI)-Fourier transform ion
      cyclotron resonance-mass spectrometry imaging (MSI), followed by infrared (IR)
      spectroscopic imaging on the same specimen. Multimodal measurements from the same
      tissue provide precise spatial alignment between modalities, enabling more
      advanced image processing such as image fusion and sharpening. Performing MSI
      first produces higher quality data from each technique compared to performing IR
      imaging before MSI. The difference is likely due to fixing the tissue section
      during MALDI matrix removal, thereby preventing analyte degradation occurring
      during IR imaging from an unfixed specimen. Leveraging the unique capabilities of
      each modality, we utilized pan sharpening of MS (mass spectrometry) ion images
      with selected bands from IR spectroscopy and midlevel data fusion. In comparison
      to sharpening with histological images, pan sharpening can employ a plethora of
      IR bands, producing sharpened MS images while retaining the fidelity of the
      initial ion images. Using Laplacian pyramid sharpening, we determine the
      localization of several lipids present within the hippocampus with high mass
      accuracy at 5 MUm pixel widths. Further, through midlevel data fusion of the
      imaging data sets combined with k-means clustering, the combined data set
      discriminates between additional anatomical structures unrecognized by the
      individual imaging approaches. Significant differences between molecular ion
      abundances are detected between relevant structures within the hippocampus, such
      as the CA1 and CA3 regions. Our methodology provides high quality multiplex and
      multimodal chemical imaging of the same tissue sample, enabling more advanced
      data processing and analysis routines.

PMID- 30188690
TI  - An Engineered Sso7d Variant Enables Efficient Magnetization of Yeast Cells.
AB  - Magnetization using cheap and minimally toxic materials, such as iron oxide
      nanoparticles can enable easy separation of cells from culture medium and is
      relevant to several industrial applications. Here, we show that cell surface
      expression of a mutant protein that binds iron oxide can enable efficient
      magnetization of yeast cells. We screened a combinatorial library of mutants
      derived from the Sso7d protein scaffold to isolate proteins that exhibit
      preferential binding to iron oxide. One of the isolated mutants, SsoFe2, was
      chosen for further characterization. Yeast cells expressing SsoFe2 as fusions to
      a cell wall protein-but not other Sso7d mutants with similar overall protein
      charge or amino acid composition-preferentially bind iron oxide when present in a
      solution with high protein concentration and in the presence of 1000-fold excess
      of competitor yeast cells. Moreover, coexpression of cell surface SsoFe2 enables
      efficient magnetic capture and separation of yeast cells expressing an enzyme
      (glucose oxidase) on the cell surface from yeast culture medium, and solutions
      with high protein concentration or containing other metal oxides. Therefore,
      SsoFe2-enabled magnetization can enable a range of industrial and biotechnology
      applications, where easy separation of cells or organelles from complex media is
      desirable.

PMID- 30188691
TI  - Circular Dichroism of Chiral Molecules in DNA-Assembled Plasmonic Hotspots.
AB  - The chiral state of a molecule plays a crucial role in molecular recognition and
      biochemical reactions. Because of this and owing to the fact that most modern
      drugs are chiral, the sensitive and reliable detection of the chirality of
      molecules is of great interest to drug development. The majority of naturally
      occurring biomolecules exhibit circular dichroism (CD) in the UV range.
      Theoretical studies and several experiments have demonstrated that this UV-CD can
      be transferred into the plasmonic frequency domain when metal surfaces and chiral
      biomolecules are in close proximity. Here, we demonstrate that the CD transfer
      effect can be drastically enhanced by placing chiral molecules, here double
      stranded DNA, inside a plasmonic hotspot. By using different particle types
      (gold, silver, spheres, and rods) and by exploiting the versatility of DNA
      origami, we were able to systematically study the impact of varying particle
      distances on the CD transfer efficiency and to demonstrate CD transfer over the
      whole optical spectrum down to the near-infrared. For this purpose, nanorods were
      also placed upright on DNA origami sheets, forming strong optical antennas.
      Theoretical models, demonstrating the intricate relationships between molecular
      chirality and achiral electric fields, support our experimental findings. From
      both experimental measurements and theoretical considerations, we conclude that
      the transferred CD is most intensive for systems with strong plasmonic hotspots,
      as we find them in relatively small gaps (5-12 nm) between spherical
      nanoparticles and preferably between the tips of nanorods.

PMID- 30188692
TI  - The Emergence of Anion-pi Catalysis.
AB  - The objective of this Account is to summarize the first five years of anion-pi
      catalysis. The general idea of anion-pi catalysis is to stabilize anionic
      transition states on aromatic surfaces. This is complementary to the
      stabilization of cationic transition states on aromatic surfaces, a mode of
      action that occurs in nature and is increasingly used in chemistry. Anion-pi
      catalysis, however, rarely occurs in nature and has been unexplored in chemistry.
      Probably because the attraction of anions to pi surfaces as such is
      counterintuitive, anion-pi interactions in general are much younger than cation
      pi interactions and remain under-recognized until today. Anion-pi catalysis has
      emerged from early findings that anion-pi interactions can mediate the transport
      of anions across lipid bilayer membranes. With this evidence for stabilization in
      the ground state secured, there was no reason to believe that anion-pi
      interactions could not also stabilize anionic transition states. As an attractive
      reaction to develop anion-pi catalysis, the addition of malonic acid half
      thioesters to enolate acceptors was selected. This choice was also made because
      without enzymes decarboxylation is preferred and anion-pi interactions promised
      to catalyze selectively the disfavored but relevant enolate addition. Concerning
      anion-pi catalysts, we started with naphthalene diimides (NDIs) because their
      intrinsic quadrupole moment is highly positive. The NDI scaffold was used to
      address questions such as the positioning of substrates on the catalytic pi
      surface or the dependence of activity on the pi acidity of this pi surface. With
      the basics in place, the next milestone was the creation of anion-pi enzymes,
      that is, enzymes that operate with an interaction rarely used in biology, at
      least on intrinsically pi-acidic or highly polarizable aromatic amino-acid side
      chains. Electric-field-assisted anion-pi catalysis addresses topics such as
      heterogeneous catalysis on electrodes and remote control of activity by voltage.
      On pi-stacked foldamers, anion-(pi) n-pi catalysis was discovered. Fullerenes
      emerged as the scaffold of choice to explore contributions from polarizability.
      On fullerenes, anionic transition states are stabilized by large macrodipoles
      that appear only in response to their presence. With this growing collection of
      anion-pi catalysts, several reactions beyond enolate addition have been explored
      so far. Initial efforts focused on asymmetric anion-pi catalysis. Increasing
      enantioselectivity with increasing pi acidity of the active pi surface has been
      exemplified for enamine and iminium chemistry and for anion-pi transaminase
      mimics. However, the delocalized nature of anion-pi interactions calls for the
      stabilization of charge displacements over longer distances. The first step in
      this direction was the formation of cyclohexane rings with five stereogenic
      centers from achiral acyclic substrates on pi-acidic surfaces. Moreover, the
      intrinsically disfavored exo transition state of anionic Diels-Alder reactions is
      stabilized selectively on pi-acidic surfaces; endo products and otherwise
      preferred Michael addition products are completely suppressed. Taken together, we
      hope that these results on catalyst design and reaction scope will establish
      anion-pi catalysis as a general principle in catalysis in the broadest sense.

PMID- 30188693
TI  - Diarylureas Containing 5-Membered Heterocycles as CB1 Receptor Allosteric
      Modulators: Design, Synthesis, and Pharmacological Evaluation.
AB  - Allosteric modulators have attracted significant interest as an alternate
      strategy to modulate CB1 receptor signaling for therapeutic benefits that may
      avoid the adverse effects associated with orthosteric ligands. Here we extended
      our previous structure-activity relationship studies on the diarylurea-based CB1
      negative allosteric modulators (NAMs) by introducing five-membered heterocycles
      to replace the 5-pyrrolidinylpyridinyl group in PSNCBAM-1 (1), one of the first
      generation CB1 allosteric modulators. Many of these compounds had comparable
      potency to 1 in blocking the CB1 agonist CP55,940 stimulated calcium mobilization
      and [35S]GTP-gamma-S binding. Similar to 1, most compounds showed positive
      cooperativity by increasing [3H]CP55,940 binding, consistent with the positive
      allosteric modulator (PAM)-antagonist mechanism. Interestingly, these compounds
      exhibited differences in ability to increase specific binding of [3H]CP55,940 and
      decrease binding of the antagonist [3H]SR141716. In saturation binding studies,
      only increases in [3H]CP55,940 Bmax, but not Kd, were observed, suggesting that
      these compounds stabilize low affinity receptors into a high affinity state.
      Among the series, the 2-pyrrolyl analogue (13) exhibited greater potency than 1
      in the [35S]GTP-gamma-S binding assay and significantly enhanced the maximum
      binding level in the [3H]CP5,5940 binding assay, indicating greater CB1 receptor
      affinity and/or cooperativity.

PMID- 30188694
TI  - mRNA Polyplexes with Post-Conjugated GALA Peptides Efficiently Target, Transfect,
      and Activate Antigen Presenting Cells.
AB  - Vaccines based on mRNA have emerged as potent systems to elicit CD8+ T cell
      responses against various cancers and viral infectious diseases. The efficient
      intracellular delivery of mRNA molecules encoding antigens into the cytosol of
      antigen-presenting cells (APCs) is still challenging, requiring cell attachment,
      active uptake, and subsequent endosomal escape. Here, we report a facile approach
      for the formulation of peptide-functionalized mRNA polyplexes using copper-free
      click chemistry to promote presentation of mRNA antigen by dendritic cells (DCs).
      After screening different membrane active peptides, GALA modified mRNA polyplexes
      (PPx-GALA) with a size around 350 nm and with a slightly negative surface charge
      (-7 mV), exhibited the highest EGFP-mRNA transfection in RAW 246.7 macrophages
      (~36%) and D1 dendritic cells (~50%) as compared to polyplexes decorated with
      melittin or LEDE peptides. Interestingly, we found that PPx-GALA enters DCs
      through sialic acid mediated endo/phagocytosis, which was not influenced by DC
      maturation. The PPx-GALA formulation exhibited 18-fold higher cellular uptake
      compared to a lipofectamine mRNA formulation without inducing cytotoxicity. Live
      cell imaging showed that PPx-GALA that were taken up by endocytosis induced
      calcein release from endosomes into the cytosol. DCs treated with PPx-GALA
      containing mRNA encoding for OVA displayed enhanced T cell responses and DC
      maturation. Collectively, these data provide a strong rationale for further study
      of this PPx-GALA formulation in vivo as a promising mRNA vaccine platform.

PMID- 30188695
TI  - Ecotoxicology in the Anthropocene: Are We Listening to Nature's Scream?

PMID- 30188696
TI  - Exploring the Reactivity of Donor-Stabilized Phosphenium Cations: Lewis Acid
      Catalyzed Reduction of Chlorophosphanes by Silanes.
AB  - Phosphane-stabilized phosphenium cations react with silanes to effect either
      reduction to primary or secondary phosphanes, or formation of P-P bonded species
      depending upon counteranion. This operates for in situ generated phosphenium
      cations, allowing catalytic reduction of P(III)-Cl bonds in the absence of strong
      reducing agents. Anion and substituent dependence studies have allowed insight
      into the competing mechanisms involved.

PMID- 30188697
TI  - In Situ Structural Study of Sb(V) Adsorption on Hematite (1102) Using X-ray
      Surface Scattering.
AB  - The binding mechanism of Sb(V) on a single-crystal hematite (1102) surface was
      studied using crystal truncation rod X-ray diffraction (CTR) under in situ
      conditions. The best-fit CTR model indicates Sb(V) adsorbs at the surface as an
      inner-sphere complex forming a tridentate binding geometry with the nearest Sb-Fe
      distance of 3.09(4) A and an average Sb-O bond length of 2.08(5) A. In this
      binding geometry, Sb is bound at both edge-sharing and corner-sharing sites of
      the surface Fe-O octahedral units. The chemical plausibility of the proposed
      structure was further verified by bond valence analysis, which also deduced a
      protonation scheme for surface O groups. The stoichiometry of the surface
      reaction predicts the release of one OH- group at pH 5.5.

PMID- 30188698
TI  - Oxygenic Photoreactivity in Photosystem II Studied by Rotating Ring Disk
      Electrochemistry.
AB  - Protein film photoelectrochemistry has previously been used to monitor the
      activity of photosystem II, the water-plastoquinone photooxidoreductase, but the
      mechanistic information attainable from a three-electrode setup has remained
      limited. Here we introduce the four-electrode rotating ring disk electrode
      technique for quantifying light-driven reaction kinetics and mechanistic pathways
      in real time at the enzyme-electrode interface. This setup allows us to study
      photochemical H2O oxidation in photosystem II and to gain an in-depth
      understanding of pathways that generate reactive oxygen species. The results show
      that photosystem II reacts with O2 through two main pathways that both involve a
      superoxide intermediate to produce H2O2. The first pathway involves the
      established chlorophyll triplet-mediated formation of singlet oxygen, which is
      followed by its reduction to superoxide at the electrode surface. The second
      pathway is specific for the enzyme/electrode interface: an exposed antenna
      chlorophyll is sufficiently close to the electrode for rapid injection of an
      electron to form a highly reducing chlorophyll anion, which reacts with O2 in
      solution to produce O2*-. Incomplete H2O oxidation does not significantly
      contribute to reactive oxygen formation in our conditions. The rotating ring disk
      electrode technique allows the chemical reactivity of photosystem II to be
      studied electrochemically and opens several avenues for future investigation.

PMID- 30188699
TI  - AFLOW-CHULL: Cloud-Oriented Platform for Autonomous Phase Stability Analysis.
AB  - A priori prediction of phase stability of materials is a challenging practice,
      requiring knowledge of all energetically competing structures at formation
      conditions. Large materials repositories-housing properties of both experimental
      and hypothetical compounds-offer a path to prediction through the construction of
      informatics-based, ab initio phase diagrams. However, limited access to relevant
      data and software infrastructure has rendered thermodynamic characterizations
      largely peripheral, despite their continued success in dictating
      synthesizability. Herein, a new module is presented for autonomous thermodynamic
      stability analysis, implemented within the open-source, ab initio framework
      AFLOW. Powered by the AFLUX Search-API, AFLOW-CHULL leverages data of more than
      1.8 million compounds characterized in the AFLOW.org repository, and can be
      employed locally from any UNIX-like computer. The module integrates a range of
      functionality: the identification of stable phases and equivalent structures,
      phase coexistence, measures for robust stability, and determination of
      decomposition reactions. As a proof of concept, thermodynamic characterizations
      have been performed for more than 1300 binary and ternary systems, enabling the
      identification of several candidate phases for synthesis based on their relative
      stability criterion-including 17 promising C15 b-type structures and 2 half
      Heuslers. In addition to a full report included herein, an interactive, online
      web application has been developed showcasing the results of the analysis and is
      located at aflow.org/aflow-chull .

PMID- 30188701
TI  - Accurate Description of Low-Lying Excited States in a Series of Photoreactive
      Clusters [Os3(CO)10(alpha-diimine)] by DFT Calculations.
AB  - Density functional theory (DFT) calculations were performed on clusters
      [Os3(CO)10(alpha-diimine)], for alpha-diimine = 2,2'-bipyridine (BPY), N
      isopropyl 2-iminomethylpyridine (IMP), and N, N'-diisopropyl-l,4-diaza-1,3
      butadiene (DAB), together with their spectroscopic study. This important family
      of clusters is known to convert upon irradiation with visible light into short
      lived biradicals and long-lived zwitterions from a sigmapi* (SBLCT) excited state
      that has not been described accurately thus far by quantum mechanical
      calculations. On the basis of the combined DFT, UV-vis absorption, and resonance
      Raman data, the lowest-lying visible absorption band is assigned to a sigma(Os1
      Os3)-to-pi*(alpha-diimine) CT transition, for alpha-diimine = bpy and IMP, and to
      a strongly delocalized sigma(Os1-Os3)pi*-to-sigma*(Os1-Os3)pi* transition for
      conjugated nonaromatic alpha-diimine = DAB. The DFT calculations rationalize the
      experimentally determined characteristics of this electronic transition in the
      studied series: (i) The corresponding absorption band is the dominant feature in
      the visible spectral region. (ii) The CT character of the electronic excitation
      declines from alpha-diimine = bpy to IMP and vanishes for DAB. (iii) The
      excitation energies decrease in the order alpha-diimine = DAB > BPY > IMP. (iv)
      The oscillator strength shrinks in the order alpha-diimine = DAB > IMP > BPY.
      Reference photoreaction quantum yields measured accurately for the formation of a
      cluster zwitterion from [Os3(CO)10(IMP)] in strongly coordinating pyridine
      demonstrate that the optical population of the lowest-energy 1sigmapi* and
      relaxed 3sigmapi* excited states in the DFT model scheme is still capable of
      inducing the initial homolytic Os1-Os3 sigma-bond splitting, although less
      efficiently than the optical excitation into neighbor higher-lying electronic
      transitions due to a higher potential barrier for the reaction from a
      dissociative (sigmasigma*) state.

PMID- 30188700
TI  - Cell Motility Facilitated by Mono(2-ethylhexyl) Phthalate via Activation of the
      AKT-beta-Catenin-IL-8 Axis in Colorectal Cancer.
AB  - Di(2-ethylhexyl) phthalate (DEHP) is a common plasticizer that is widely used in
      many consumer products and medical devices. Humans can be exposed to DEHP through
      ingestion, inhalation, or dermal absorption. Previous studies on DEHP have
      focused on its role as an endocrine-disrupting chemical leading to endocrine
      related diseases. However, the correlation between DEHP exposure and the
      progression of colorectal cancer (CRC) is largely unknown. The aim of this study
      was to investigate the effects of mono(2-ethylhexyl) phthalate (MEHP), an active
      metabolite of DEHP, on the progression of CRC. Our results showed that treatment
      with MEHP enriched the population of cancer-stem-cell (CSC)-like cells and
      upregulated IL-8 expression by inducing the AKT-beta-catenin-TCF4 signaling
      pathway. Blocking beta-catenin-TCF4-mediated IL-8 expression reversed the MEHP
      induced migration and enrichment of CSC-like cells. Consistent with the in vitro
      data, DEHP treatment increased the levels of nuclear beta-catenin, polyp
      formation, and invasive adenocarcinoma in a mouse model. Our results suggest that
      MEHP facilitates the progression of CRC through AKT-beta-catenin signaling.

PMID- 30188703
TI  - Coupled Cluster and Time-Dependent Density Functional Theory Description of Inner
      Shell Photoabsorption Cross Sections of Molecules.
AB  - Near K-edge photoabsorption cross section spectra of a number of molecules,
      namely, water, ammonia, acetone, acetaldehyde, furan, and pyrrole, were obtained
      at the nitrogen, oxygen, and carbon K-edges with the Coupled Cluster ansatz (CC)
      and with the Time-Dependent Density Functional Theory (TDDFT) by treating the
      inner shell excitations as individual channels, separated from the valence part
      of the spectrum. The discretized electronic pseudospectrum, obtained with
      quadratically integrable basis sets ( a.k.a. L2) at the CC or TDDFT level, is
      used to reconstruct the complex dipole polarizability function, from which the
      photoabsorption cross section near the K-edge is obtained by a continued fraction
      based analytic continuation procedure. The CC2 and CCSD results are in good
      agreement with experimental data, while the TDDFT results yield reliable cross
      sections. Overall, the results obtained in this work indicate that our method can
      be used for the treatment of the NEXAFS spectra, with the advantage that the
      electronic excitations in the K-edges can be easily obtained at low computational
      cost using TDDFT.

PMID- 30188702
TI  - Eugenol Confers Cadmium Tolerance via Intensifying Endogenous Hydrogen Sulfide
      Signaling in Brassica rapa.
AB  - Eugenol, a plant-derived small compound, shows great medicinal potential.
      However, whether and how eugenol regulates crop physiology remains elusive. Here
      we reported that eugenol induced Cd (cadmium) tolerance in the root of Brassica
      rapa. Roots were treated with eugenol and CdCl2 simultaneously (eugenol + Cd) or
      pretreated with eugenol followed by CdCl2 treatment (eugenol -> Cd). Eugenol
      significantly attenuated Cd-induced growth inhibition, ROS accumulation,
      oxidative injury, and cell death, which were confirmed by in vivo histochemical
      analysis. Eugenol remarkably decreased free Cd2+ accumulation in root. Eugenol
      intensified GSH (glutathione) accumulation in roots upon CdCl2 exposure, which
      explained the decrease in free Cd2+ and attenuation of oxidative injury. Eugenol
      stimulated endogenous H2S (hydrogen sulfide) generation by upregulating the
      expression of BrLCD ( l-cysteine desulfhydrase) and BrDCD ( d-cysteine
      desulfhydrase) as well as their enzymatic activities in CdCl2-treated root.
      Application of H2S biosynthesis inhibitor or H2S scavenger led to the decrease in
      endogenous H2S level in Cd-treated root, which further compromised all the above
      effects of eugenol. These findings suggested that eugenol triggered H2S -> GSH
      signaling cassette in plants to combat Cd stress, which shed new light on eugenol
      modulated plant physiology and the interaction between eugenol and H2S.

PMID- 30188704
TI  - Dispersion-Corrected DFT Struggles with Predicting Three-Body Interaction
      Energies.
AB  - We demonstrate that the dispersion-corrected density functional theory (DFT-D)
      schemes fall short of predicting reliable three-body interaction energies. This
      concerns also a popular variant of DFT-D called the "many-body dispersion" (MBD)
      method, which might seem surprising in the light of the fact that its name
      contains the very phrase "many-body". The main reason for the inaccuracy of the
      three-body interaction energies in the DFT-D schemes can be attributed to
      internal deficiencies of the standard DFT functionals that the existing "-D"
      methods are incapable of correcting since the main problems emerge from the terms
      not related to the dispersion component. At present, it seems that none of the a
      posteriori dispersion techniques are able to predict accurately the total
      interaction energy for a supermolecular system together with its simultaneous
      decomposition into the many-body components. On the other hand, if one is
      interested only in the three-body interaction energies, we propose an adjustment
      to the MBD approach that achieves good accuracy in conjunction with the
      supermolecular MP2.

PMID- 30188705
TI  - Size Fractionation of Dissolved Organic Nitrogen in Peatland Fluvial Systems.
AB  - Understanding the nature and fate of nitrogen (N) in freshwater systems is
      crucial for assessing the risk of eutrophication. However, there is a paucity of
      information on the characterization of fluvial N in upland peat-dominated
      environments. Here, we employ a combination of field sampling and tangential flow
      ultrafiltration (TFU) to investigate the concentrations and fluxes of low
      molecular weight (LMW) and high molecular weight (HMW) dissolved organic N (DON)
      in a peatland stream-reservoir system in the south Pennines (UK). Our TFU results
      show that ~26% of DON concentration is LMW DON and represents an estimated
      fluvial flux of 3.07 +/- 22 kg N ha-1 during the study period. Our mass balance
      results reveal that the reservoir retains 71% of LMW DON input, which accounts
      for ~25% retention of bioavailable (dissolved inorganic N + LMW DON) N. Our study
      suggests that current understanding of inorganic N as the sole source of
      bioavailable N with eutrophic significance in upland freshwaters requires a
      reappraisal. Evaluation of ecosystem response to increased loading of N needs to
      include a consideration of LMW DON.

PMID- 30188706
TI  - Synthesis of Selenium and Tellurium Core-Modified Azuliporphyrinogens and
      Benziporphyrinogens and Corresponding Carbaporphyrinoids.
AB  - The synthesis of selenium and tellurium core-modified carbaporphyrinogens was
      carried out by the reaction of functional selenophene/tellurophene diols with
      azulene or a benzitripyrrane in the presence of acid. The products were obtained
      in moderate yields and were characterized by using 1H and 13C NMR, UV-vis, FT-IR,
      CV, and HRMS spectroscopic techniques. Further, oxidation of the obtained core
      modified carbaporphyrinogens in the presence of DDQ in CHCl3 afforded the
      corresponding carbaporphyrins in good yields. Benziporphyrins showed no
      indication of a ring current or macrocyclic aromaticity as confirmed by using
      proton NMR spectroscopy, but the addition of TFA gave rise to the formation of
      weakly diatropic dications.

PMID- 30188707
TI  - The Wild West of E-Cigarettes.
AB  - The popularity of e-cigarettes is growing exponentially. Yet, the health risks
      associated with their use remain unclear, mainly due to the fact that they are
      not "one product", but a combination of ever-evolving designs, flavors, brands,
      and modes of use. Research needs to better understand how these variables affect
      toxicity.

PMID- 30188708
TI  - Peloruside E (22-Norpeloruside A), a Pelorusane Macrolide from the New Zealand
      Marine Sponge Mycale hentscheli, Retains Microtubule-Stabilizing Properties.
AB  - A new peloruside congener, peloruside E (5), has been isolated in sub-milligram
      quantities from a specimen of the New Zealand marine sponge Mycale hentscheli.
      The structure of 5 differs from the parent compound peloruside A (1) by
      replacement of the C-10 gem-dimethyl moiety with a monomethyl substituent and
      represents the first structural deviation in the pelorusane scaffold. Peloruside
      E (5) is potently antiproliferative (HL-60, IC50 90 nM, cf. 1, 19 nM) and
      polymerizes purified tubulin, albeit at a rate lower than that of 1.

PMID- 30188709
TI  - Down-Regulation of the Androgen Receptor by G-Quadruplex Ligands Sensitizes
      Castration-Resistant Prostate Cancer Cells to Enzalutamide.
AB  - Stabilization of the G-quadruplexes (G4s) within the androgen receptor (AR) gene
      promoter to block transcription may represent an innovative approach to interfere
      with aberrant AR signaling in castration resistant prostate cancer (CRPC). A
      library of differently functionalized naphthalene diimides (NDIs) was screened
      for their ability to stabilize AR G4s: the core-extended NDI (7) stood out as the
      most promising ligand. AR-positive cells were remarkably sensitive to 7 in
      comparison to AR-negative CRCP or normal prostate epithelial cells; 7 induced
      remarkable impairment of AR mRNA and protein amounts and significant
      perturbations in the expression levels of KLK3 and of genes involved in the
      activation of AR program via feedback mechanisms. Moreover, 7 synergistically
      interacted with Enzalutamide, an inhibitor of AR signaling used in second-line
      therapies. Overall, our data show that stabilization of AR G4s may represent an
      alternative treatment options for CRPC and other malignancies relying on aberrant
      androgen signaling.

PMID- 30188710
TI  - D-A-D Structured Bis-acylhydrazone Exhibiting Aggregation-Induced Emission,
      Mechanochromic Luminescence, and Al(III) Detection.
AB  - A readily accessible D-A-D triad molecule 1 was synthesized through acylhydrazone
      bond formation using carefully chosen building blocks. The molecule 1 exhibits
      emission through charge-coupled proton transfer and enhanced emission induced
      through aggregation and mechanochromic luminescence. Further, it detects Al(III)
      selectively among other cations in an efficient manner.

PMID- 30188711
TI  - Effects of Intense Electric Fields on the Double Proton Transfer in the Watson
      Crick Guanine-Cytosine Base Pair.
AB  - The double proton transfer reaction in the guanine-cytosine (GC) base pair is
      studied, using density functional theory, to understand the chances of mutations
      under the effect of uniform electric fields in the order of 108 to 109 V m-1. On
      the basis of potential energy surfaces, reaction Gibbs energies, equilibrium
      constants, imaginary frequencies, forward and reverse barrier heights, tunneling
      corrected rate constants, half-lives of the forward and reverse reactions,
      percent tautomerization, and Boltzmann distributions, it was found that fields
      >=+3.60 * 109 V m-1 facilitate the mutation in the GC base pair and reduce the
      rectification of point mutations. Fields applied along the double proton transfer
      in the - x (defined in the C to G direction) direction favor the canonical over
      the rare tautomers. Tunneling-corrected rate constants of the forward reaction
      increase exponentially with stronger fields in the - x direction and follow a
      Gaussian curve for the reverse reaction.

PMID- 30188712
TI  - Theoretical Study of the Histidine-catalyzed Asymmetric Aldol Reaction of Acetone
      and Benzaldehyde.
AB  - The mechanism of histidine-catalyzed asymmetrical aldol reaction of acetone with
      benzaldehyde was studied by using B3LYP method of density functional theory at
      the levels of 6-31G(d,p) and cc-pvdz basis sets. The calculation results showed
      that the reaction mechanism included four steps: (I) nucleophilic attack of
      histidine on acetone to form alcohol intermediate Inter-A through the transition
      state TS1 (considered a rate control step because the activation energy (49.95
      kcal/mol) was relatively high); (II) dehydration of the alcohol intermediate to
      form the cis- or trans-enamine through the transition states TS3 and TS4 with the
      energy barriers of 36.12 and 38.15 kcal/mol; (III) electrophilic addition of cis
      enamine or trans-enamine with benzaldehyde to form imine Inter-C or Inter-E
      through the transition states TS8, TS9, TS10, and TS11 (energy barriers 18.43,
      22.34, 13.24, and 13.24 kcal/mol, respectively); (IV) after combination of the
      imine intermediate with water through the transition states TS12, TS13, TS14, and
      TS15 (energy barriers 22.79, 34.6, 28.2, 25.12 kcal/mol, respectively), removal
      of the histidine catalys to obtain the final S or R aldol product. Through
      analyzing the potential energy profile of reaction, we found that the histidine
      catalyzed reaction of acetone with benzaldehyde was more energetically favorable
      to obtain the R-product (ee value >99%). Solvent effects computed with a
      polarizable continuum model (PCM) indicated that the DMSO and water can reduce
      the reaction energy barrier.

PMID- 30188713
TI  - Dispersion Energy of Symmetry-Adapted Perturbation Theory from the Explicitly
      Correlated F12 Approach.
AB  - Methods of the explicitly correlated F12 approach are applied to the problem of
      calculating the uncoupled second-order dispersion energy in symmetry-adapted
      perturbation theory. The accuracy of the new method is tested for noncovalently
      bound complexes from the A24 data set [J. Rezac and P. Hobza, J. Chem. Theory
      Comput. 2013, 9, 2151] using standard orbital basis sets aug-cc-pV XZ
      supplemented with auxiliary aug-cc-pV XZ_OPTRI sets. For near equilibrium
      geometries, it is possible to recover the dispersion energy with average relative
      errors consistently smaller than 0.1% (with respect to the CBS extrapolated limit
      estimated from regular orbital calculations). This level of accuracy is achieved
      already in the basis set of a triple-zeta quality, when a Slater-type correlation
      factor exp(-0.9 r12) is combined with variant C of the F12 approach. The
      explicitly correlated approach clearly outperforms regular orbital calculations
      in the basis set of quintuple-zeta quality (average relative errors of 1%).

PMID- 30188714
TI  - Disorder Foreshadows Order in Colloidal Cubes.
AB  - Monte Carlo simulations are used to investigate the mechanism of the disorder-to
      order phase transition for a bulk system of colloidal hard cubes. It is observed
      that the structure of the ordered state is foreshadowed in the disordered state
      through multiple spontaneously occurring ordered domains. Such domains arise due
      to the entropic preference for local facet alignment between particles and occur
      transiently and sparsely throughout the system even in the stable isotropic
      phase. At pressures (and degrees of supersaturation) where the isotropic phase
      becomes marginally metastable, a classical nucleation process is never observed;
      instead, the ordered domains increase in number and size, eventually reaching a
      critical point where they percolate the entire system and spontaneously
      consolidate to form the ordered phase. The critical number of particles and the
      per particle free-energy barrier both decrease with pressure. Using the total
      number of locally ordered particles as a global order parameter, it is predicted
      that for large systems the ordering transition would only be spontaneous above a
      critical pressure. Finally, a test designed to probe the ability of the system to
      favor a single monodomain solid from initially misaligned-ordered domains,
      reveals that an active interdomain zone mediates the concerted reorientation of
      particles.

PMID- 30188715
TI  - How Ligand Protonation State Controls Water in Protein-Ligand Binding.
AB  - The role of water in protein-ligand binding has been an intensely studied topic
      in recent years; however, how ligand protonation state change perturbs water has
      not been considered. Here we show that water dynamics and interactions can be
      controlled by the protonation state of ligand using continuous constant pH
      molecular dynamics simulations of two closely related model systems, beta
      secretase 1 and 2 (BACE1 and BACE2), in complex with a small-molecule inhibitor.
      Simulations revealed that, upon binding, the inhibitor pyrimidine ring remains
      deprotonated in BACE1 but becomes protonated in BACE2. Pyrimidine protonation
      results in water displacement, rigidification of the binding pocket, and shift in
      the ligand binding mode from water-mediated to direct hydrogen bonding. These
      findings not only support but also rationalize the most recent structure
      selectivity data in BACE1 drug design. Binding-induced protonation state changes
      are likely common; our work offers a glimpse at how modeling protein-ligand
      binding while allowing ligand titration can further advance the understanding of
      water and structure-based drug design.

PMID- 30188716
TI  - Vibrational Kinetics in Plasma as a Functional Problem: A Flux-Matching Approach.
AB  - A new approach to calculate the vibrational distribution function of molecules in
      a medium providing energy for vibrational excitation is proposed and
      demonstrated. The approach is an improvement of solution methods based on the
      drift-diffusion Fokker-Planck (FP) equation for a double differentiable function
      representing the vibrational populations on a continuum internal energy scale. A
      self-consistent numerical solution avoids approximations used in previous
      analytical solutions. The dissociation flux, a key parameter in the FP equation,
      is fixed using the kinetics of molecular dissociation from near-continuum levels,
      so that the vibrational kinetics becomes a functional problem. The approach is
      demonstrated for the kinetics of asymmetric stretching of CO2, showing that it
      represents an alternative, potentially much more efficient in computational
      terms, to the presently usual state-to-state approach which is based on the
      kinetics of the populations of individual levels, and gives complementary insight
      into the dissociation process.

PMID- 30188717
TI  - GEX1A, a Polyketide from Streptomyces chromofuscus, Corrects the Cellular Defects
      Associated with Niemann-Pick Type C1 in Human Fibroblasts.
AB  - We report the first evidence of GEX1A, a polyketide known to modulate alternative
      pre-mRNA splicing, as a potential treatment for Niemann-Pick type C disease.
      GEX1A was isolated from its producing organism, Streptomyces chromofuscus, and
      screened in NPC1 mutant cells alongside several semisynthetic analogues. We found
      that GEX1A and analogues are capable of restoring cholesterol trafficking in NPC1
      mutant fibroblasts, as well as altering the expression of NPC1 isoforms detected
      by Western blot. These results, along with the compound's favorable
      pharmacokinetic properties, highlight the potential of spliceosome-targeting
      scaffolds such as GEX1A for the treatment of genetic diseases.

PMID- 30188718
TI  - Mechanistic and Kinetic Investigations on the Thermal Unimolecular Reaction of
      Heptafluoroisobutyronitrile.
AB  - Heptafluoroisobutyronitrile (C4) has been utilized as a dielectric compound to
      replace sulfur hexafluoride for the sake of environmental concern. Energetic
      profiles of the potential energy surface for the unimolecular reaction of C4 were
      calculated using density functional theory (M06-2X), quadratic complete basis set
      (CBS-QB3), Gaussian-4, multireference Rayleigh-Schrodinger perturbation theory
      (RS2, RS2C), and state-averaged multiconfiguration self-consistent-field (SA
      MCSCF) ab initio methods. Among 38 production channels, the most energetically
      accessible reaction path is the three-centered rearrangement of cyanide to
      isocyanide. The C-CF3 bond appears to be the weakest bond in C4(X1A') and the
      symmetry-breaking C-CF3 bond cleavage undergoes to form the ground-state
      CF3(X2A1) and CF3CFCN (X2A") radicals. All the possible isomerization pathways
      involving F- and CF3-migration together with the concerted elimination and
      stepwise decomposition routes were revealed for C4 and i-C4. Various isomers and
      potential toxic byproducts including FCN, CF3CN, C2F5CN, CF2?CFCF3, CF2?CFCN,
      CF4, C2F6, and alkyne compounds have been identified for the first time. Master
      equation analysis has been carried out to obtain the temperature- and pressure
      dependent thermal rate constants. Theoretical kinetics for the loss of C4 due to
      pyrolysis is in good agreement with the temperature-ramped flow-tube experiment.
      The present theoretical work provides new insights on the thermal stability and
      chemical reactivity of C4. Moreover, i-C4 and C2F6 are proposed to be the
      potential characteristic gas molecules to monitor the insulation breakdown of C4
      in the electric equipment.

PMID- 30188719
TI  - Amino Acid Hot Spots of Halogen Bonding: A Combined Theoretical and Experimental
      Case Study of the 5-HT7 Receptor.
AB  - A computational approach combining a structure-activity relationship library of
      halogenated and the corresponding unsubstituted ligands (called XSAR) with QM
      based molecular docking and binding free energy calculations was used to search
      for amino acids frequently targeted by halogen bonding (hot spots) in a 5-HT7R as
      a case study. The procedure identified two sets of hot spots, extracellular
      (D2.65, T2.64, and E7.35) and transmembrane (C3.36, T5.39, and S5.42), which were
      further verified by a synthesized library of halogenated arylsulfonamide
      derivatives of (aryloxy)ethylpiperidines. It was found that a halogen bond formed
      between T5.39 and a bromine atom at 3-position of the aryloxy fragment caused the
      most remarkable, 35-fold increase in binding affinity for 5-HT7R when compared to
      the nonhalogenated analog. The proposed paradigm of halogen bonding hot spots was
      additionally verified on D4 dopamine receptor showing that it can be used in
      rational drug design/optimization for any protein target.

PMID- 30188720
TI  - Metal- and Acid-Free C-H Formylation of Nitrogen Heterocycles: Using Trioxane as
      an Aldehyde Equivalent Enabled by an Organic-Soluble Oxidant.
AB  - A metal-free, innate, and practical C-H formylation of nitrogen heterocycles
      using trioxane as a formyl equivalent is reported. This reaction provides a mild
      and robust method for modifying medicinally relevant heterocycles with an
      aldehyde handle. The use of an organic soluble oxidant, tetrabutylammonium
      persulfate, is critical in promoting the desired coupling.

PMID- 30188721
TI  - Evaporation Mass Flux: A Predictive Model and Experiments.
AB  - Evaporation is a fundamental and core phenomenon in a broad range of disciplines
      including power generation and refrigeration systems, desalination,
      electronic/photonic cooling, aviation systems, and even biosciences. Despite its
      importance, the current theories on evaporation suffer from fitting coefficients
      with reported values varying in a few orders of magnitude. Lack of a sound model
      impedes simulation and prediction of characteristics of many systems in these
      disciplines. Here, we studied evaporation at a planar liquid-vapor interface
      through a custom-designed, controlled, and automated experimental setup. This
      experimental setup provides the ability to accurately probe thermodynamic
      properties in vapor, liquid, and close to the liquid-vapor interface. Through
      analysis of these thermodynamic properties in a wide range of evaporation mass
      fluxes, we cast a predictive model of evaporation based on nonequilibrium
      thermodynamics with no fitting parameters. In this model, only the interfacial
      temperatures of liquid and vapor phases along with the vapor pressure are needed
      to predict evaporation mass flux. The model was validated by the reported study
      of an independent research group. The developed model provides a foundation for
      all liquid-vapor phase change studies including energy, water, and biological
      systems.

PMID- 30188722
TI  - Dual Lewis Acid/Photoredox-Catalyzed Addition of Ketyl Radicals to Vinylogous
      Carbonates in the Synthesis of 2,6-Dioxabicyclo[3.3.0]octan-3-ones.
AB  - A combined Lewis acid/photoredox catalyst system enabled the intramolecular
      umpolung addition of ketyl radicals to vinylogous carbonates in the synthesis of
      2,6-dioxabicyclo[3.3.0]octan-3-ones. This reaction proceeded on a variety of
      aromatic ketones to provide THF rings in good yield (up to 95%). Although
      diastereoselectivity was found to be modest (1.4-5:1) for the C-C bond forming
      reaction, the minor diastereomers were converted to 2,6-dioxabicyclo[3.3.0]octan
      3-ones by an efficient Lewis acid-mediated epimerization cascade in up to 90%
      yield.

PMID- 30188723
TI  - Visible-Light-Mediated Iminyl Radical Generation from Benzyl Oxime Ether:
      Synthesis of Pyrroline via Hydroimination Cyclization.
AB  - The treatment of an  O-(4-methoxybenzyl) oxime ether bearing an olefin
      substituent and 1-chloroanthraquinone (1-Cl-AQN) catalyst in 2-butanone under
      visible-light irradiation affords pyrroline via an iminyl radical intramolecular
      hydroimination. Mechanistic studies indicate that iminyl radical generation
      mainly proceeds by hydrogen abstraction of the photocatalyst from the benzyl
      position of the oxime. Moreover, the hydrogen atom was identified in circulation
      from the benzylic position of the substrates between AQN and 2-butanone to quench
      the carbon radical without requiring any additional reagents.

PMID- 30188724
TI  - Design, Synthesis, and Application of Highly Reducing Organic Visible-Light
      Photocatalysts.
AB  - A series of inexpensive, easily tunable, and highly reducing organic
      photocatalysts (PCs) that exhibit strong absorption in the visible region are
      described. Time-dependent density functional theory calculations were applied to
      corroborate the experimental observations and explain the relationship between
      the structure and property. The photocatalytic efficiency of these PCs was
      demonstrated by catalyzing several challenging reactions and the radical cascade
      cyclization of 1,6-diyne with superior photocatalytic efficiency to other organic
      photocatalysts.

PMID- 30188725
TI  - Micro-Refractometry and Local-Field Mapping with Single Molecules.
AB  - The refractive index n is one of the most important materials parameters of
      solids and, in recent years, has become the subject of significant
      interdisciplinary interest, especially in nanostructures and meta-materials. It
      is, in principle, a macroscopic quantity, so its meaning on a length scale of a
      few nanometers, i.e., well below the wavelength of light, is not clear a priori
      and is related to methods of its measurement on this length scale. Here we
      introduce a novel experimental approach for mapping the effective local value
      [Formula: see text] of the refractive index in solid films and the analysis of
      related local-field enhancement effects. The approach is based on the imaging and
      spectroscopy of single chromophore molecules at cryogenic temperatures. Since the
      fluorescence lifetime T1 of dye molecules in a transparent matrix depends on the
      refractive index due to the local density of the electromagnetic field (i.e., of
      the photon states), one can obtain the local [Formula: see text] values in the
      surroundings of individual chromophores simply by measuring their T1 times.
      Spatial mapping of the local [Formula: see text] values is accomplished by
      localizing the corresponding chromophores with nanometer accuracy. We demonstrate
      this approach for a polycrystalline n-hexadecane film doped with terrylene.
      Unexpectedly large fluctuations of local-field effects and effective [Formula:
      see text] values (the latter between 1.1 and 1.9) were found.

PMID- 30188726
TI  - Enhanced Magnetoresistance in Chiral Molecular Junctions.
AB  - Chirality-induced spin selectivity (CISS) is a recently discovered effect, whose
      precise microscopic origin has not yet been fully elucidated; it seems, however,
      clear that spin-orbit interaction plays a pivotal role. Various model Hamiltonian
      approaches have been proposed, suggesting a close connection between spin
      selectivity and filtering and helical symmetry. However, first-principles studies
      revealing the influence of chirality on the spin polarization are missing. To
      clearly demonstrate the influence of the helical conformation on the spin
      polarization properties, we have carried out spin-dependent Density-Functional
      Theory (DFT) based transport calculations for a model molecular system. It
      consists of alpha-helix and beta-strand conformations of an oligo-glycine
      peptide, which is bonded to a nickel electrode and to a gold electrode in a two
      terminal setup, similar to a molecular junction or a local probe, for example, in
      STM or AFM configurations. We have found that the alpha-helix conformation
      displays a spin polarization, calculated through the intrinsic magneto-resistance
      of the junction, about 100-1000 times larger than the linear beta-strand, clearly
      demonstrating the crucial role played by the molecular helical geometry on the
      enhancement of spin polarization associated with the CISS effect.

PMID- 30188727
TI  - Programmable Metal/Semiconductor Nanostructures for mRNA-Modulated Molecular
      Delivery.
AB  - Cytotoxic chemotherapeutics are important tools for the clinical treatment of a
      variety of solid tumors. However, their use is often complicated by multidrug
      resistance that can develop in patients, limiting the potencies of these agents.
      New strategies are needed to provide versatile systems that can respond to and
      disable resistance mechanisms. We demonstrate the use of a new family of
      materials, programmable metal/semiconductor nanostructures, for drug delivery and
      mRNA sensing in drug-resistant cells. These materials are composed of a central
      core gold nanoparticle surrounded by a layer of DNA-capped quantum dots. The
      modularity of these "core-satellite" assemblies allows for the construction of
      superstructures with controlled size and the incorporation of multiple
      functionalities for drug delivery. The DNA sequence within the nanoparticle
      specifically binds to an mRNA encoding an important drug resistance factor, MRP1,
      inside cancer cells, releasing a potent anticancer drug doxorubicin. This event
      triggers a turn-on fluorescence emission along with a downregulation of the MRP1
      drug efflux pump, a main resistance factor for doxorubicin, yielding a remarkable
      improvement in therapeutic efficacy against drug-resistant cancer cells. This
      work paves the way for the development of programmable materials with multiple
      synergistic functionalities for biomedical applications.

PMID- 30188728
TI  - Signatures of Exciton Delocalization and Exciton-Exciton Annihilation in
      Fluorescence-Detected Two-Dimensional Coherent Spectroscopy.
AB  - Incoherently detected coherent multidimensional spectroscopy is rapidly gaining
      popularity, promising a different application range and sensitivity than its
      traditional counterpart. While measuring the same response, the two methods are
      not equivalent. We present calculations of the fluorescence-detected coherent two
      dimensional (F-2DES) spectra of a molecular heterodimer. We compare how the F
      2DES technique differs from standard coherently detected two-dimensional (2DES)
      spectroscopy in measuring exciton delocalization. We analyze which processes
      contribute to cross-peaks in the zero-waiting-time spectra obtained by the two
      methods. Strictly on the basis of time-dependent perturbation theory, we study
      how in both methods the varying degree of cancellation between perturbative
      contributions gives rise to cross-peaks and we identify exciton annihilation and
      exciton relaxation contributions to the cross-peak in the zero-waiting-time F
      2DES. We propose that time-gated fluorescence detection can be used to isolate
      the annihilation contribution to F-2DES both to retrieve information equivalent
      to 2DES spectroscopy and to study the annihilation contribution itself.

PMID- 30188729
TI  - Polyurethane Nanoparticle-Loaded Fenofibrate Exerts Inhibitory Effects on
      Nonalcoholic Fatty Liver Disease in Mice.
AB  - Polyurethane (PU) nanoparticles are potential drug carriers. We aimed to study
      the in vitro and in vivo efficacy of biodegradable PU nanoparticles loaded with
      fenofibrate (FNB-PU) on nonalcoholic fatty liver disease (NAFLD). FNB-PU was
      prepared by a green process, and its preventive effects on NAFLD were
      investigated on HepG2 cells and mice. FNB-PU showed sustained in vitro FNB
      release profile. Compared to FNB crude drug, FNB-PU significantly decreased
      triglyceride content in HepG2 cells incubated with oleic acid and in livers of
      mice with NAFLD induced by a methionine choline deficient diet, and increased
      plasma FNB concentration of the mice. FNB-PU increased absorption of FNB and
      therefore enhanced the inhibitory effects of FNB on NAFLD.

PMID- 30188730
TI  - Tetrahydrobenzofuran-6(2 H)-one Neolignans from Ocotea heterochroma: Their
      Platelet Activating Factor (PAF) Antagonistic Activity and in Silico Insights
      into the PAF Receptor Binding Mode.
AB  - Three new tetrahydrobenzofuran-6(2 H)-one-type neolignans, heterochromins A-C (1
      3), along with a bicyclo[3.2.1]octane neolignan, cinerin C (4), were isolated
      from an ethanol extract from the leaves of Ocotea heterochroma, a native plant
      growing in the Colombo-Ecuadorian region of the Andes. The chemical structures of
      1-3 were elucidated by spectroscopic methods. The platelet activating factor
      (PAF) antagonistic activity was tested in vitro for these compounds.
      Additionally, their binding mode to the PAF receptor was studied by molecular
      docking and molecular dynamics simulations in order to rationalize such activity.
      Heterochromin A (1) was found to be a potent PAF antagonist with a favorable
      molecular profile for interacting with the PAF receptor binding site.

PMID- 30188731
TI  - Probing ATP/ATP-Aptamer or ATP-Aptamer Mutant Complexes by Microscale
      Thermophoresis and Molecular Dynamics Simulations: Discovery of an ATP-Aptamer
      Sequence of Superior Binding Properties.
AB  - Microscale thermophoresis (MST) is used to follow the dissociation constants
      corresponding to ATTO 488-labeled adenosine triphosphate (ATP) and the ATP
      aptamer or ATP-aptamer mutants that include two binding sites for the ATP ligand.
      A set of eight ATP-aptamer mutants, where the thymidine bases, within the
      reported ATP binding aptamer sites, are substituted with cytosine bases, are
      examined. The MST-derived dissociation constant of ATP to the reported aptamer is
      Kd = 31 +/- 3 MUM, whereas most of the aptamer mutants show lower affinity
      (higher Kd values) toward the ATP ligand. One aptamer mutant reveals, however, a
      higher affinity toward the ATP ligand, as compared to the reported ATP-aptamer.
      Molecular dynamics and docking simulations identify the structural features that
      control the affinities of binding of the ATP ligand to the two binding sites
      associated with the ATP-aptamer or the ATP-aptamer mutants. The simulated
      structures suggest that H-bonds between the ATP ligand and G9 and G11 bases,
      within one binding domain, and the pi-pi interactions between G6 and the ATP
      purine moiety and the pyrimidine ring, in the second binding domain, control the
      affinity of binding interactions between the ATP ligand and the ATP-aptamer or
      ATP-aptamer mutant. Very good correlation between the computed  Kd values and the
      MST-derived Kd values is found. The ATP-aptamer mutant (consisting of A1-> G, T4 
      > C, T12 -> C, A24 -> G, and T27 -> C mutations) reveals superior binding
      affinities toward the ATP ligands ( Kd = 15 +/- 1 MUM) as compared to the binding
      affinity of ATP to the reported aptamer. These features of the mutant are
      supported by molecular dynamics simulations.

PMID- 30188732
TI  - Iridium-Catalyzed Isomerization of N-Sulfonyl Aziridines to Allyl Amines.
AB  - The Crabtree's reagent catalyzes the isomerization of N-sulfonyl 2,2
      disubstituted aziridines to allyl amines. The selectivity of allyl amine vs imine
      is very high (up to 99/1). The unprecedented isomerization takes place in mild
      conditions without activation of the catalyst by hydrogen. The mechanism has been
      studied computationally by DFT calculations; instead of the usual hydrogenation
      of COD, the catalytic species is formed by a loss of the pyridine ligand.
      Approaching of aziridine to this unsaturated species leads to a carbocation
      intermediate through a low energy barrier. A metal-mediated tautomerization
      involving sequentially gamma-H elimination and N-H reductive elimination affords
      selectively the allyl amine. The readiness of the CgammaH bond to participate in
      the H elimination step accounts for the selectivity toward the allyl amine
      product.

PMID- 30188734
TI  - Insights into Current Tropomyosin Receptor Kinase (TRK) Inhibitors: Development
      and Clinical Application.
AB  - The use of kinase-directed precision medicine has been heavily pursued since the
      discovery and development of imatinib. Annually, it is estimated that around ~20
      000 new cases of tropomyosin receptor kinase (TRK) cancers are diagnosed, with
      the majority of cases exhibiting a TRK genomic rearrangement. In this
      Perspective, we discuss current development and clinical applications for TRK
      precision medicine by providing the following: (1) the biological background and
      significance of the TRK kinase family, (2) a compilation of known TRK inhibitors
      and analysis of their cocrystal structures, (3) an overview of TRK clinical
      trials, and (4) future perspectives for drug discovery and development of TRK
      inhibitors.

PMID- 30188735
TI  - Lonely Atoms with Special Gifts: Breaking Linear Scaling Relationships in
      Heterogeneous Catalysis with Single-Atom Alloys.
AB  - We discuss a simple yet effective strategy for escaping traditional linear
      scaling relations in heterogeneous catalysis with highly dilute bimetallic alloys
      known as single-atom alloys (SAAs). These systems, in which a reactive metal is
      atomically dispersed in a less reactive host, were first demonstrated with the
      techniques of surface science to be active and selective for hydrogenation
      reactions. Informed by these early results, PdCu and PtCu SAA nanoparticle
      hydrogenation catalysts were shown to work under industrially relevant
      conditions. To efficiently survey the many potential metal combinations and
      reactions, simulation is crucial for making predictions about reactivity and
      guiding experimental focus on the most promising candidate materials. This recent
      work reveals that the high surface chemical heterogeneity of SAAs can result in
      significant deviations from Bronsted-Evans-Polanyi scaling relationships for many
      key reaction steps. These recent insights into SAAs and their ability to break
      linear scaling relations motivate discovery of novel alloy catalysts.

PMID- 30188736
TI  - Molecular Dynamics Study on Wettability of Poly(vinylidene fluoride) Crystalline
      and Amorphous Surfaces.
AB  - The present study investigates the effect of microscopic structure on the
      wettability of poly(vinylidene fluoride) (PVDF) surfaces using all-atom molecular
      dynamics simulations of water droplets brought into contact with both crystal and
      amorphous PVDF surfaces. For each case, computations were performed using five
      different droplet diameters, and the corresponding water droplet contact angles
      theta were obtained. Using the fact that the cosine of these contact angles for
      both surfaces are inversely proportional to the radius of the droplet contact
      surface ( rdr( Z0)), the contact angle thetainfinity of the macroscopic water
      droplet was obtained by extrapolating cos theta to 1/ rdr( Z0) = 0. The estimated
      values of thetainfinity on the crystal and amorphous surfaces were 96 degrees 
      and 86 degrees , respectively, showing that the amorphous surface is less
      hydrophobic than the crystal surface. The contact angle of the
      crystalline/amorphous mixed surface was estimated using the Cassie equation to be
      91 degrees . This value agrees well with experimental measurement of the water
      contact angle on the PVDF film. Furthermore, the interaction energy, interface
      structure, and electrostatic potential were analyzed to clarify the reason for
      the lower hydrophobicity of the amorphous surface. This surface interacts more
      favorably with water than the crystal surface. Such an interaction reduces the
      excess free energy (interfacial tension) at the PVDF and water interface and
      makes the amorphous surface less hydrophobic. The amorphous interfacial region
      contains more water molecules than the crystal one, and water molecules are
      oriented toward the PVDF. This interface structure makes water strongly interact
      with the PVDF.

PMID- 30188737
TI  - Does Systemic Sclerosis-associated Interstitial Lung Disease Burn Out? Specific
      Phenotypes of Disease Progression.
AB  - RATIONALE: Previous studies have suggested that interstitial lung disease (ILD)
      progresses most rapidly early in the course of systemic sclerosis-associated
      (SSc)-ILD, and that SSc-ILD is often more stable or even "burned out" after the
      first 4 years following diagnosis. OBJECTIVES: Our objectives were to determine
      whether an apparent plateau in pulmonary function decline is due to survival bias
      and to identify distinct prognostic phenotypes of ILD progression. METHODS:
      Consecutive patients with SSc-ILD from a single center were included. Pulmonary
      function measurements were typically performed every 6 months. Study participants
      were categorized into long-term survivors (>8 yr survival from diagnosis), and
      those with medium-term and short-term mortality (4-8 and <4 yr survival,
      respectively). We excluded those censored with less than 8 years of follow-up.
      Subject-specific slopes for change in forced vital capacity (FVC) and diffusing
      capacity of the lung for carbon monoxide (DlCO) were calculated using generalized
      linear models with mixed effects. The rate of decline in FVC was compared across
      prognostic groups. RESULTS: The cohort included 171 study participants with SSc
      ILD. A plateau in the progression of FVC was apparent in the full cohort analysis
      but disappeared with stratification into prognostic subgroups to account for
      survival bias. Those with short-term mortality had a higher annual rate of
      decline in FVC (-4.10 [95% confidence interval (CI), -7.92 to -0.28] vs. -2.14
      [95% CI, -3.31 to -0.97] and -0.94 [-1.46 to -0.42]; P = 0.003) and DlCO (-5.28
      [95% CI, -9.58 to -0.99] vs. -3.13 [95% CI, -4.35 to -1.92] and -1.32 [95% CI, 
      2.01 to -0.63]; P < 0.001) than those with medium-term mortality and long-term
      survival with adjustment for age, sex, and pack-years. Change in FVC in the
      previous year did not predict FVC change in the subsequent year. CONCLUSIONS:
      Adults with SSc-ILD have distinct patterns of physiological progression that
      remain relatively consistent during long-term follow-up; however, recent change
      in FVC cannot be used to predict future change in FVC within shorter follow-up
      intervals. The findings of this study provide important information on the course
      of disease in SSc-ILD and identify specific phenotypes of progression that may
      improve clinical decision-making and design of future therapeutic trials.

PMID- 30188738
TI  - Managing side effects in adjuvant endocrine therapy for breast cancer.
AB  - INTRODUCTION: Recent improvements in the survival of hormone-responsive breast
      cancer are strongly associated with therapeutic advances, particularly with the
      uptake of adjuvant endocrine therapy. Nevertheless, endocrine therapy is also
      linked with adverse effects that impact quality of life, social function, and
      adherence to treatment. Areas covered: This review examines the spectrum and
      consequences of adverse effects of tamoxifen and aromatase inhibitors, and the
      pharmacological and non-pharmacological approaches to mitigate some of the most
      frequent and disturbing side effects of endocrine therapy (including vasomotor,
      musculoskeletal, and vulvovaginal symptoms). The authors performed a qualitative
      analysis of English papers indexed in PubMed through May 2017, including meta
      analysis, randomized controlled trials, observational studies, and systematic
      reviews. Expert commentary: Side effects of endocrine treatments are frequent and
      often underestimated in the care of breast cancer survivors, leading to a poor
      adherence to treatments that can compromise oncological outcomes. Many of the
      most common adverse events can be mitigated through pharmacological and non
      pharmacological approaches that should be discussed and offered to patients in a
      dedicated setting of care.

PMID- 30188740
TI  - Ferumoxytol for the treatment of iron deficiency anemia.
AB  - INTRODUCTION: Ferumoxytol is a superparamagnetic molecule originally developed as
      a contrast agent for magnetic resonance imaging. Elemental iron is contained
      within the carbohydrate core and is released slowly after infusion allowing a
      large dose of iron to be administered in a short period of time. Ferumoxytol,
      originally approved for iron deficiency in chronic kidney disease, received a
      broad label for any cause of iron deficiency after oral iron intolerance or in
      those circumstances when oral iron is ineffective or harmful. Areas covered: The
      chemistry, pharmacology and pharmacokinetics of ferumoxytol were reviewed.
      Retrospective, observational, and prospective phase II and III trials were
      reviewed. When appropriate, comparative safety and efficacy parameters were
      reported. Differentiation between minor infusion reactions and more severe
      hypersensitivity reactions that may lead to anaphylaxis is described. Expert
      commentary: Ferumoxytol is a safe and effective iron formulation providing a
      means of iron repletion in persons with iron deficiency with or without anemia.
      Relative to iron sucrose, ferric gluconate, and iron dextran and similar to
      ferric carboxymaltose and iron isomaltoside, ferumoxytol yields relatively low
      quantities of labile free iron. Hypersensitivity and anaphylaxis is extremely
      rare. Hypophosphatemia with ferumoxytol's administration is extremely rare.
      Optimal strategies for application of ferumoxytol-enhanced imaging and full
      replacement dosing in a single setting remain to be determined.

PMID- 30188739
TI  - Interferon Gamma-Induced Protein (IP-10) as Potential Biomarker for Cancer
      Related-Fatigue: Results from a 6-month Randomized Controlled Trial.
AB  - : We examined if serum concentrations Interferon gamma-induced protein (IP-10) is
      a potential clinical biomarker for cancer-related-fatigue (CRF). Fatigue scores
      and IP-10 concentrations were measured from curatively treated fatigued cancer
      patients randomized to either cognitive behavioral therapy (CBT, n = 26) or
      waiting-list (WL, n = 13). No correlation was found between baseline IP-10 level
      and fatigue severity and no significant differences in IP-10 serum levels were
      observed between fatigued and matched non-fatigued patients (n = 22). Relative
      changes in IP-10 concentrations from baseline to six-month follow-up were not
      significantly different between the CBT and WL conditions. In this study, IP-10
      showed low potential as clinical CRF biomarker. TRIAL REGISTRATION: This study is
      registered at ClinicalTrials.gov (NCT01096641).

PMID- 30188741
TI  - Can listeners hear the difference between children with normal hearing and
      children with a hearing impairment?
AB  - Acoustic measurements have shown that the speech of hearing-impaired (HI)
      children differs from that of normally hearing (NH) children, even after several
      years of device use. This study focuses on the perception of HI speech in
      comparison to NH children's speech. The purpose of this study was to investigate
      whether adult listeners can identify the speech of NH and HI children. Moreover,
      it is studied whether listeners' experience and the children's length of device
      use play a role in that assessment. For this study, short utterances of 7
      children with a cochlear implant (CI), 7 children with an acoustic hearing aid
      (HA) and 7 children with NH were presented to 90 listeners who were required to
      specify the hearing status of each speech sample. The judges had different
      degrees of familiarity with hearing disorders: there were 30 audiologists, 30
      primary schoolteachers and 30 inexperienced listeners. The results show that the
      speech of children with NH and HI can reliably be identified. However, listeners
      do not manage to distinguish between children with CI and HA. Children with CI
      are increasingly identified as NH with increasing length of device use. For
      children with HA, there is no similar change with longer device use. Also,
      experienced listeners seem to display a more lenient attitude towards atypical
      speech, whereas inexperienced listeners are stricter and generally consider more
      utterances to be produced by children with HI.

PMID- 30188742
TI  - Selecting the appropriate pharmacotherapy for epilepsy in patients with
      Alzheimer's disease.

PMID- 30188743
TI  - The Turkish version of the MedRisk instrument for measuring patient satisfaction:
      measurement properties in physical therapy care among inpatients.
AB  - PURPOSE: Our aim was to cross culturally adapt the MedRisk instrument for
      measuring patient satisfaction with physical therapy care for Turkish-speaking
      inpatients, provide information about its measurement properties, and determine
      the socio-demographic factors influencing satisfaction of Turkish patients.
      METHOD: This was a cross-sectional, measurement-focused study. The MedRisk
      instrument for measuring patient satisfaction was translated and adapted into
      Turkish. Two hundred four inpatients with different health conditions from
      different units of a large university hospital were assessed using the Turkish
      version of the MedRisk instrument for measuring patient satisfaction. Forty-two
      patients were reassessed after 72 h. Construct validity, internal consistency,
      convergent validity, criterion-referenced validity, floor and ceiling effects,
      and test-retest reliability were evaluated. RESULTS: Factor analysis showed a two
      factor structure. Cronbach's alpha values for the internal consistency ranged
      between 0.49 and 0.81. Corrected item-total correlations ranged between 0.29 and
      0.72. Intraclass correlation coefficients ranged between 0.67 and 0.97, standard
      errors of measurement ranged between 0.34 and 2.61 points, and substantially good
      agreement was achieved. Eleven of twelve items were positively correlated with
      the global measures. No floor or ceiling effects were detected. The satisfaction
      level of inpatients was high. CONCLUSIONS: Our results suggested that the Turkish
      version of the MedRisk instrument for measuring patient satisfaction is a quite
      reliable and valid measurement to evaluate patient satisfaction with physical
      therapy care in Turkish-speaking inpatients. We determined that Turkish
      inpatients are highly satisfied with their physical therapy care, and they
      consider the patient-physical therapist relationship important. Implications for
      rehabilitation The Turkish version of the MedRisk instrument for measuring
      patient satisfaction is a reliable and valid translation of the original MedRisk
      instrument for measuring patient satisfaction. However, it should be noted that
      three items from the original version were excluded. Clinicians and relevant
      researchers can use this instrument to evaluate satisfaction with physical
      therapy care among Turkish-speaking inpatients.

PMID- 30188744
TI  - Radiotherapy for Melanoma with Perineural Invasion: University of Florida
      Experience.
AB  - PURPOSE: Outcomes after adjuvant radiotherapy for cutaneous melanoma with
      perineural invasion (PNI). METHODS: Seven patients (5 cutaneous, 2 recurrent
      nerve lesions) received radiotherapy. RESULTS: At a median 4.5 years: Two
      patients did not recur; no local failures occurred. Three patients who omitted
      nodal irradiation developed regional failures (2 out-of-field, 1 in-field). Three
      patients developed distant metastases. Four died with disease (median, 3.6
      years); 1 died from intercurrent disease (13.0 years). Two are alive without
      disease (6.8 and 11.6 years). No patient experienced grade >=3 toxicity.
      CONCLUSIONS: Postoperative radiotherapy can reduce local recurrences; primary
      radiotherapy for unresectable disease is recommended.

PMID- 30188745
TI  - DPP4 inhibition by sitagliptin attenuates LPS-induced lung injury in mice.
AB  - Acute respiratory distress syndrome (ARDS) is a severe clinical condition marked
      by acute respiratory failure and dysregulated inflammation. Pulmonary vascular
      endothelial cells (PVEC) function as an important pro-inflammatory source in
      ARDS, suggesting that modulation of inflammatory events at the endothelial level
      may have therapeutic benefit. Dipeptidyl peptidase-4 (DPP4) inhibitors, widely
      used for the treatment of diabetes mellitus, have been reported to have possible
      anti-inflammatory effects. However, the potential anti-inflammatory effects of
      DPP4 inhibition on PVEC function and ARDS pathophysiology are unknown. Therefore,
      we evaluated the effects of sitagliptin, a DPP4 inhibitor in wide clinical use,
      on LPS-induced lung injury in mice and in human lung endothelial cells (EC) in
      vitro. In vivo, sitagliptin reduced serum DPP4 activity, BAL protein
      concentration, cell number and pro-inflammatory cytokine levels, after LPS, and
      alleviated histological findings of lung injury. LPS decreased the expression
      levels of CD26/DPP4 on pulmonary epithelial cells and PVEC isolated from mouse
      lungs, and the effect was partially reversed by sitagliptin. In vitro, human lung
      microvascular EC (HLMVEC) expressed higher levels of CD26/DPP4 than human
      pulmonary arterial EC. LPS induced release of TNFalpha, IL-6, and IL-8 by HLMVEC
      that was inhibited by sitagliptin. LPS promoted proliferation of HLMVEC, and
      sitagliptin suppressed this response. However, sitagliptin failed to reverse LPS
      induced permeability in cultured EC or lung epithelial cells in vitro. In
      summary, sitagliptin attenuates LPS-induced lung injury in mice and exerts anti
      inflammatory effects on HLMVEC. These novel observations indicate DPP4 inhibitors
      may have potential as therapeutic drugs for ARDS.

PMID- 30188746
TI  - High molecular weight hyaluronan ameliorates allergic inflammation and airway
      hyperresponsiveness in the mouse.
AB  - Allergic asthma is a major cause of morbidity in both pediatric and adult
      patients. Recent research has highlighted the role of hyaluronan, an
      extracellular matrix glycosaminoglycan, in asthma pathogenesis. Experimental
      allergic airway inflammation and clinical asthma are associated with an increase
      of shorter fragments of hyaluronan (sHA), which complex with inter-alpha
      inhibitor heavy chains (HC) and induce inflammation and airway
      hyperresponsiveness (AHR). Importantly, the effects of sHA can be antagonized by
      the physiological counterpart high-molecular-weight hyaluronan (HMWHA). We used a
      mouse model of house dust mite-induced allergic airway inflammation and
      demonstrate that instilled HMWHA ameliorated allergic airway inflammation and
      AHR, even when given after the establishment of allergic sensitization and after
      challenge exposures. Furthermore, instilled HMWHA reduced the development of HA
      HC complexes, and the activation of Rho-Associated, Coiled-Coil Containing
      Protein Kinase 2 (ROCK2). We conclude that airway application of HMWHA is a
      potential treatment for allergic airway inflammation.

PMID- 30188747
TI  - Interaction between the retrotrapezoid nucleus and the parafacial respiratory
      group to regulate active expiration and sympathetic activity in rats.
AB  - The retrotrapezoid nucleus (RTN) contains chemosensitive cells that distribute
      CO2-dependent excitatory drive to the respiratory network. This drive facilitates
      the function of the respiratory central pattern generator (rCPG) and increases
      sympathetic activity. It is also evidenced that during hypercapnia, the late
      expiratory (late-E) oscillator in the parafacial respiratory group (pFRG) is
      activated and determine the emergence of active expiration. However, it remains
      unclear the microcircuitry responsible for the distribution of the excitatory
      signals to the pFRG and the rCPG in conditions of high CO2. Herein, we
      hypothesized that excitatory inputs from chemosensitive neurons in the RTN are
      necessary for the activation of late-E neurons in the pFRG. Using the
      decerebrated in situ rat preparation, we found that lesions of neurokinin-1
      receptor (NK1R)-expressing neurons in the RTN region with substance P-saporin
      conjugate (SSP-SAP) suppressed the late-E activity in abdominal (AbN) and
      sympathetic (SN) nerves, and attenuated the increase in phrenic nerve (PN)
      activity induced by hypercapnia. On the other hand, kynurenic acid (100 mM)
      injections in the pFRG eliminated the late-E activity in AbN and tSN, but did not
      modify PN response during hypercapnia. Iontophoretic injections of retrograde
      tracer into the pFRG of adult rats revealed labeled phox2b-expressing neurons
      within the RTN. Our findings are supported by mathematical modeling of
      chemosensitive and late-E populations within the RTN and pFRG regions as two
      separate but interacting populations, in a way that the activation of the pFRG
      late-E neurons during hypercapnia requires glutamatergic inputs from the RTN
      neurons that intrinsically detect changes in CO2/pH.

PMID- 30188748
TI  - Mitochondrial peptides cause proinflammatory responses in the alveolar epithelium
      via FPR-1, MAPKs, and AKT: a potential mechanism involved in acute lung injury.
AB  - Acute lung injury (ALI) is characterized by alveolar epithelial damage and
      uncontrolled pulmonary inflammation. Mitochondrial damage-associated molecular
      patterns (DAMPs), including mitochondrial peptides (N-formyl peptides, NFPs), are
      released during cell injury and death and induce inflammation by unclear
      mechanisms. In this study, we have investigated the role of mitochondrial DAMPs
      (MTDs), especially NFPs, in alveolar epithelial injury and lung inflammation. In
      murine models of ALI, high levels of mitochondrial NADH dehydrogenase 1 in
      bronchoalveolar lavage fluid (BALF) were associated with lung injury scores and
      increased formyl peptide receptor (FPR)-1 expression in the alveolar epithelium.
      Cyclosporin H (CsH), a specific inhibitor of FPR1, inhibited lung inflammation in
      the ALI models. Both MTDs and NFPs upon intratracheal challenge caused
      accumulation of neutrophils into the alveolar space with elevated BALF levels of
      mouse chemokine KC, interleukin-1beta and nitric-oxide and increased pulmonary
      FPR-1 levels. CsH significantly attenuated MTDs or NFP-induced inflammatory lung
      injury and activation of MAPKs and AKT pathways. FPR1 expression was present in
      rat primary alveolar epithelial type II cells (AECIIs) and was increased by MTDs.
      CsH inhibited MTDs or NFP-induced CINC-1/IL-8 release and phosphorylation of p38,
      JNK, and AKT in rat AECII and human cell line A549. Inhibitors of MAPKs and AKT
      also suppressed MTD-induced IL-8 release and NF-kappaB activation. Collectively,
      our data indicate an important role of the alveolar epithelium in initiating
      immune responses to MTDs released during ALI. The potential mechanism may involve
      increase of IL-8 production in MTD-activated AECII through FPR-1 and its
      downstream MAPKs, AKT, and NF-kappaB pathways.

PMID- 30188749
TI  - UPPS-P facets of impulsivity and alcohol use patterns in college and noncollege
      emerging adults.
AB  - BACKGROUND: Alcohol use and related problems reach a peak in emerging adulthood.
      Impulsivity is a multifaceted construct known to be involved in emerging adult
      alcohol use. Few studies have examined impulsivity and alcohol use across both
      college attending and noncollege attending emerging adults. OBJECTIVES: To
      clarify the multifaceted nature of impulsivity and its links to emerging adult
      alcohol use, this study investigated whether the five distinct facets of the UPPS
      P model of impulsivity were predictive of three different behavioral outcomes:
      alcohol intake, alcohol related problems and binge drinking. In addition, the
      moderating effects of college attendance were tested. METHODS: A community sample
      comprising 273 Australian college and noncollege attendees (58.6% women; 41.4%
      men) aged between 18 and 30 years (Mage = 23.71, SD = 2.81). RESULTS: Multiple
      regression analyses demonstrated that lack of premeditation predicted alcohol
      intake and binge drinking behavior, whilst positive and negative urgency
      predicted alcohol related problems. Moderation analyses revealed that the effects
      of impulsivity on alcohol patterns were consistent for college and noncollege
      attending emerging adults. CONCLUSION: These findings highlight the importance of
      impulsive urgency (both positive and negative) in emerging adult problematic
      alcohol use, and support the generalizability of college samples to broader
      emerging adult populations. Emerging adults may use alcohol to avoid negative
      mood states and further enhance positive mood states. Improved emotional
      regulation may help both college and non-college emerging adults reduce their
      alcohol use.

PMID- 30188750
TI  - A rotating light cycle promotes weight gain and hepatic lipid storage in mice.
AB  - Processes involved in regulation of energy balance and intermediary metabolism
      are aligned to the light-dark cycle. Shift-work and high fat diet (HFD)-induced
      obesity disrupt circadian rhythmicity and are associated with increased risk of
      non-alcoholic fatty liver disease (NAFLD). This study aimed to determine the
      effect of simulating shift work on hepatic lipid accumulation in lean and HFD
      mice. C57BL/6 mice fed a standard laboratory diet (SLD) or HFD for 4wks were
      further allocated to a normal light (NL)-cycle (lights on:0600-1800hr) or
      rotating light (RL)-cycle (3-days NL and 4-days reversed (lights on:1800-0600hr)
      repeated) for 8wks. Tissue was collected every 3hrs beginning at 0600hr. HFD-mice
      gained more weight than SLD-mice, and RL-mice gained more weight than NL-mice.
      SLD-NL and HFD-NL mice, but not RL-mice, were more active, had higher respiratory
      quotients and consumed/expended more energy during the dark phase compared to the
      light phase. Blood glucose and plasma cholesterol and triglyceride concentrations
      were elevated in HFD and SLD-RL compared to SLD-NL mice. Hepatic glycogen was
      elevated in HFD compared to SLD-mice. Hepatic triglycerides were elevated in SLD
      RL and HFD-mice compared to SLD-NL. Circadian rhythmicity of hepatic acetyl-CoA
      carboxylase (ACACA) mRNA was phase shifted in SLD-RL and HFD-NL and lost in HFD
      RL mice. Hepatic ACACA protein was reduced in SLD-RL and HFD-mice compared to SLD
      NL mice. Hepatic adipose triglyceride lipase was elevated in HFD-NL compared to
      SLD-NL but lower in RL-mice compared to NL-mice irrespective of diet. 
      Conclusion: A RL-cycle model of shift-work promotes weight gain and hepatic lipid
      storage even in lean conditions.

PMID- 30188751
TI  - Small adipose stores in cystic fibrosis mice are characterized by reduced cell
      volume, not cell number.
AB  - Cystic fibrosis (CF) is a lethal genetic disorder that affects many organ systems
      of the body, including various endocrine and exocrine tissues. Health and
      survival positively associate with body mass and as a consequence, CF clinical
      care includes high-fat, high-calorie diets to maintain and increase adipose
      tissue stores. Such strategies have been implemented without a clear
      understanding of the cause and effect relationship between body mass and
      patients' health. Here, we use CF mouse models, which display small adipose
      stores, to begin examining body fat as a prelude into mechanistic studies of low
      body growth in CF, so that optimal therapeutic strategies can be developed. We
      reasoned that low adiposity must result from reduced number and/or volume of
      adipocytes. To determine relative contribution of either mechanism, we quantified
      volume of intraperitoneal and subcutaneous adipocytes. We found smaller, but not
      fewer, adipocytes in CF compared to wildtype (WT) animals. Specifically,
      intraperitoneal CF adipocytes were half the volume of WT cells, whereas
      subcutaneous cells were less affected by the Cftr genotype. No differences were
      found in cell types between CF and WT adipose tissues. Adipose tissue CFTR mRNA
      was detected and we found greater CFTR expression in intraperitoneal depots as
      compared with subcutaneous samples. RNA sequencing revealed that CF adipose
      tissue exhibited lower expression of several key genes of adipocyte function
      (Lep, Pck1, Fas, Jun), consistent with low triglyceride storage. The data
      indicate that CF adipocytes contain less triglycerides than WT cells and a role
      for CFTR in these cells is proposed.

PMID- 30188752
TI  - Growth differentiation factor 11 ameliorates experimental colitis by inhibiting
      NLRP3 inflammasome activation.
AB  - Growth differentiation factor 11 (GDF11) has an anti-inflammatory effect in the
      mouse model of atherosclerosis and Alzheimer's disease, but how GDF11 regulates
      intestinal inflammation during ulcerative colitis (UC) is poorly defined. The
      NLRP3 (Nod-like receptor family pyrin domain-1 containing 3) inflammasome is
      closely associated with intestinal inflammation due to its ability to increase IL
      1beta secretion. Our aim is to determine whether GDF11 has an effect on
      attenuating experimental colitis in mice. In this study, using a dextran sulfate
      sodium (DSS)-induced acute colitis mouse model, we reported that GDF11 treatment
      attenuated loss of body weight, the severity of the disease activity index (DAI),
      shortening of the colon, and histological changes in the colon. GDF11 remarkably
      suppressed IL-1beta secretion and NLRP3 inflammasome activation in colon samples
      and RAW264.7 cells, such as the levels of NLRP3 and activated caspase-1.
      Furthermore, we found that GDF11 inhibited NLRP3 inflammasome activation by
      downregulating the TLR4/NF-kappaB p65 pathway and reactive oxygen species (ROS)
      production via the typical Smad2/3 pathway. Thus, our research shows that GDF11
      alleviates DSS-induced colitis by inhibiting NLRP3 inflammasome activation,
      providing some basis for its potential use in the treatment of UC.

PMID- 30188753
TI  - Chronic ethanol-mediated hepatocyte apoptosis links to decreased TET1 and 5
      hydroxymethylcytosine formation.
AB  - The 5-hydroxymethylcytosine (5hmc) is a newly identified epigenetic modification
      thought to be regulated by the TET family of proteins. Little information is
      available about how ethanol consumption may modulate 5hmC formation and alcoholic
      liver disease (ALD) progression. A rat ALD model was used to study 5hmC in
      relationship to hepatocyte apoptosis. Human ALD liver samples were also used to
      validate these findings. It was found that chronic ethanol feeding significantly
      reduced 5hmC formation in a rat ALD model. There were no significant changes in
      TET2 and TET3 between the control- and ethanol-fed animals. In contrast,
      methylcytosine dioxygenase TET1 (TET1) expression was substantially reduced in
      the ethanol-fed rats and was accompanied by increased hepatocyte apoptosis.
      Similarly, knockdown of TET1 in human hepatocyte-like cells also significantly
      promoted apoptosis. Down-regulation of TET1 resulted in elevated expression of
      the DNA damage marker, suggesting a role for 5hmc in hepatocyte DNA damage as
      well. Mechanistic studies revealed that inhibition of TET1 promoted apoptotic
      gene expression. Similarly, targeting TET1 activity by removing cosubstrate
      promoted apoptosis and DNA damage. Furthermore, treatment with 5-azacitidine
      significantly mimics these effects, suggesting that chronic ethanol consumption
      promotes hepatocyte apoptosis and DNA damage by diminishing TET1-mediated 5hmC
      formation and DNA methylation. In summary, the current study provides a novel
      molecular insight that TET1-mediated 5hmC is involved in hepatocyte apoptosis in
      ALD progression.-Ji, C., Nagaoka, K., Zou, J., Casulli, S., Lu, S., Cao, K. Y.,
      Zhang, H., Iwagami, Y., Carlson, R. I., Brooks, K., Lawrence, J., Mueller, W.,
      Wands, J. R., Huang, C.-K. Chronic ethanol-mediated hepatocyte apoptosis links to
      decreased TET1 and 5-hydroxymethylcytosine formation.

PMID- 30188755
TI  - Characterization of heat shock protein 27 in extracellular vesicles: a potential
      anti-inflammatory therapy.
AB  - Previously, we reported that elevated serum levels of heat shock protein 27
      (HSP27) are predictive of a lower risk of having a heart attack, stroke, or death
      from cardiovascular disease. Moreover, augmenting HSP27 (or the murine ortholog,
      HSP25) attenuated experimental atherogenesis, reduced inflammation, and lowered
      cholesterol levels. Recently, we noted that HSP27 activates NF-kappaB via TLR-4,
      resulting in attenuation of plaque inflammation; however, the precise anti
      atherosclerosis mechanisms mediated by extracellular HSP27 are incompletely
      understood. Our purpose in this study was to investigate the existence of HSP27
      in extracellular vesicles (EVs) and whether HSP27 elicited atheroprotective
      effects on target cells. Here, we provide evidence that HSP27 localizes to EVs
      derived from THP-1 cells using transmission electron microscopy (TEM) and
      immunogold labeling, Western blotting, ELISA, and fluorescence-activated cell
      sorting. TEM imaging indicated that HSP27 is found at the exosomal membrane.
      Multiple reactor monitor-mass spectrometric analysis of large vesicles, which
      included microparticles and exosomes, isolated from human plasma, also led to
      detection of HSP27 using the unique signature peptide, R.LFDQAFGLPR.L. Studies
      using THP-1 and human embryonic kidney cells show that HSP27-laden exosomes
      significantly stimulated NF-kappaB activation ( P < 0.001) and release of IL-10 (
      P < 0.0001), suggesting that HSP27 may be important exosomal cargo with
      beneficial anti-inflammatory effects.-Shi, C., Ulke-Lemee, A., Deng, J., Batulan,
      Z., O'Brien, E. R. Characterization of heat shock protein 27 in extracellular
      vesicles: a potential anti-inflammatory therapy.

PMID- 30188754
TI  - Up-regulation of miR-210 induced by a hypoxic microenvironment promotes breast
      cancer stem cells metastasis, proliferation, and self-renewal by targeting E
      cadherin.
AB  - Breast cancer stem cells (BCSCs), a small subset of breast cancer cells with stem
      cell-like properties, are essential in tumor formation, metastasis, resistance to
      anticancer therapies, and cancer recurrence. MicroRNAs (miRNAs) are involved in
      tumorigenicity by regulating specific oncogenes and tumor-suppressor genes, and
      their roles in BCSCs are becoming apparent. A novel, 3-dimensional (3D),
      semisolid culture system was established to culture MCF-7 spheroid cells with
      high percentage of BCSCs. The differences in miRNA expression among the MCF-7
      parental cells, BCSC-enriched MCF-7 spheroid cells, and CD44+/CD24- MCF-7 cells
      were evaluated by miRNA microarray, and the high expression of miR-210 in MCF-7
      spheroid cells and CD44+/CD24- MCF-7 cells was verified by quantitative RT-PCR.
      MCF-7 cells were cultured in a hypoxic chamber to detect the effect of hypoxia on
      miR-210 expression and the stemness of the cells. The 3-(4,5-dimethylthiazol-2-
      yl)-2,5-diphenyl tetrazolium bromide (MTT), transwell, and sphere-formation
      assays were performed to detect the proliferation, migration, and self-renewal
      ability of miR-210-overexpressed MCF-7 cells and MCF-7 spheroid cells with miR
      210 knocked down. The target of miR-210 was validated with a dual-luciferase
      reporter assay and Western blotting. In vivo xenograft assay and metastasis assay
      were performed to study the effects of miR-210 targeting E-cadherin on BCSCs
      growth and lung metastasis, and the tumors were assessed by immunohistochemistry
      and immunofluorescence. We developed a novel 3D, semisolid culture system to
      culture MCF-7 spheroid cells, which are enriched in BCSCs, and found, by
      performing miRNAs expression profiling, miR-210 was up-regulated in those cells
      compared with MCF-7 parental cells. High miR-210 expression was also detected in
      CD44+/CD24- MCF-7 cells and human CD44+/CD24- breast cancer cells, which was
      demonstrated to be partially due to the hypoxic microenvironment around BCSCs in
      MCF-7 spheroids or solid tumors. Ectopic expression of miR-210 in MCF-7 cells
      promoted their migration, invasion, proliferation, and self-renewal in both in
      vitro and in vivo studies. We further reported that miR-210 suppressed E-cadherin
      expression by targeting the open reading frame region of E-cadherin mRNA and by
      up-regulation of E-cadherin transcription repressor, Snail. Accordingly, E
      cadherin overexpression compromises the migration, invasion, proliferation, and
      self-renewal ability of miR-210-overexpressed MCF-7 both in vitro and in vivo.
      These findings reveal a novel regulatory pathway centered on hypoxia-mediated miR
      210 targeting of E-cadherin, which contributes to the properties and breast
      tumorigenesis of BCSCs.-Tang, T., Yang, Z., Zhu, Q., Wu, Y., Sun, K., Alahdal,
      M., Zhang, Y., Xing, Y., Shen, Y., Xia, T., Xi, T., Pan, Y., Jin, L. Up
      regulation of miR-210 induced by a hypoxic microenvironment promotes breast
      cancer stem cells metastasis, proliferation, and self-renewal by targeting E
      cadherin.

PMID- 30188756
TI  - Turning fibroblasts into cardiomyocytes: technological review of cardiac
      transdifferentiation strategies.
AB  - To date, no viable therapeutic options exist for the effective and sustained
      reversal of cardiac failure, other than heart transplantation and mechanical
      circulatory assist devices. Therefore, divergent strategies aiming at the de novo
      formation of contractile tissue, as a prerequisite for the restoration of cardiac
      pump function, are currently being pursued. Clinical trials involving the
      transplantation of somatic progenitor cells failed. The search for alternative
      cell-based strategies to combat the consequences of ischemic injury has sparked
      widespread interest in the genetic and pharmacologic reprogramming of fibroblasts
      into cardiomyocytes, harnessing the abundant in vivo pool of cardiac fibroblasts.
      Here, we provide a comprehensive overview of in vitro and in vivo cardiac
      reprogramming studies identified in an extensive literature search. We
      systematically review and evaluate feasibility, efficiency, and reproducibility
      of the different technologies currently being explored. Finally, we discuss
      potential safety issues deduced from preclinical studies and identify obstacles
      that must be overcome before clinical translation.-Klose, K., Gossen, M., Stamm,
      C. Turning fibroblasts into cardiomyocytes: technological review of cardiac
      transdifferentiation strategies.

PMID- 30188757
TI  - Sphingosine-1-phosphate (S1P) induces potent anti-inflammatory effects in vitro
      and in vivo by S1P receptor 4-mediated suppression of 5-lipoxygenase activity.
AB  - Sphingosine-1-phosphate (S1P) is involved in the regulation of important cellular
      processes, including immune-cell trafficking and proliferation. Altered S1P
      signaling is strongly associated with inflammation, cancer progression, and
      atherosclerosis; however, the mechanisms underlying its (patho)physiologic
      effects are only partially understood. This study evaluated the effects of S1P in
      vitro and in vivo on the biosynthesis of leukotrienes (LTs), which form a class
      of lipid mediators involved in the pathogenesis of inflammatory diseases. Here,
      we report for the first time that S1P potently suppresses LT biosynthesis in Ca2+
      ionophore-stimulated intact human neutrophils. S1P treatment resulted in
      intracellular Ca2+ mobilization, perinuclear translocation, and finally
      irreversible suicide inactivation of the LT biosynthesis key enzyme 5
      lipoxygenase (5-LO). Agonist studies and S1P receptor mRNA expression analysis
      provided evidence for a S1P receptor 4-mediated effect, which was confirmed by a
      functional knockout of S1P4 in HL60 cells. Systemic administration of S1P in wild
      type mice decreased both macrophage and neutrophil migration in the lungs in
      response to LPS and significantly attenuated 5-LO product formation, whereas
      these effects were abrogated in 5-LO or S1P4 knockout mice. In summary, targeting
      the 5-LO pathway is an important mechanism to explain S1P-mediated
      (patho)physiologic effects. Furthermore, agonism at S1P4 represents a novel
      effective strategy in pharmacotherapy of inflammation.-Fettel, J., Kuhn, B.,
      Guillen, N. A., Surun, D., Peters, M., Bauer, R., Angioni, C., Geisslinger, G.,
      Schnutgen, F., Meyer zu Heringdorf, D., Werz, O., Meybohm, P., Zacharowski, K.,
      Steinhilber, D., Roos, J., Maier, T. J. Sphingosine-1-phosphate (S1P) induces
      potent anti-inflammatory effects in vitro and in vivo by S1P receptor 4-mediated
      suppression of 5-lipoxygenase activity.

PMID- 30188758
TI  - The Burden of Silicosis in Michigan: 1988-2016.
AB  - RATIONALE: Exposure to respirable crystalline silica causes silicosis, a
      preventable, progressive occupational lung disease. A more rigorous occupational
      health standard for silica could help protect silica-exposed workers. OBJECTIVES:
      To describe trends over 29 years of silicosis surveillance in Michigan. METHODS:
      Michigan law requires the reporting of silicosis. We confirmed the diagnosis of
      silicosis in reported cases using medical questionnaires, review of medical
      records, and chest radiographs. The Michigan Occupational Safety and Health
      Administration (OSHA) conducted enforcement inspections at the workplaces of the
      silicosis cases, including air monitoring for silica and evaluation of workplace
      medical surveillance programs. RESULTS: The Michigan surveillance program
      identified 1,048 silicosis cases from 1988 to 2016, which decreased from 620
      during 1988-1997, to 292 during 1998-2007, to 136 during 2008-2016. The
      cumulative incidence rate of silicosis decreased from 3.7 to 1.4 to 0.7 cases per
      100,000 men 40 years of age and older in Michigan over the same three periods.
      African Americans had a higher cumulative incidence rate of silicosis, with 6.0
      cases per 100,000 African American men 40 years of age and older in Michigan
      compared with 1.2 cases per 100,000 white men 40 years of age and older in
      Michigan. The cases identified had severe disease; 59% had progressive massive
      fibrosis or category 2 or 3 small opacities per B-reading classification of the
      chest radiograph. Seventeen percent reported ever having active tuberculosis. On
      spirometry, 76% of ever smokers and 72% of never smokers demonstrated either a
      restrictive or an obstructive pattern. Most (65%) had not applied for workers'
      compensation benefits; the percentage who applied for benefits decreased from 42%
      to 28-16% over the three periods. Thirty-four of 55 (62%) workplace inspections
      found exposures above the new OSHA 50 MUg/m3 respirable crystalline silica
      permissible exposure limit, and only 11% of inspected companies screened their
      workers for silicosis. CONCLUSIONS: Adults with confirmed cases of silicosis have
      advanced disease and morbidity. Most are not using workers' compensation to pay
      for their care. The new OSHA silica standard, which lowers the permissible
      exposure limit for silica and requires medical monitoring to identify workers
      with silicosis, will help reduce the burden of silica exposure. It is critical
      for pulmonologists to be vigilant to recognize and manage this preventable
      occupational lung disease.

PMID- 30188759
TI  - A new look at molecular biology of breast cancer.
AB  - In the past 25 years, incidence rates of breast cancer have risen about 30% in
      westernized countries. Mutations in BRCA1 and BRCA2 are the most prominent cause
      of breast cancer. However, these cancer susceptibility genes (BRCAs) only account
      for a few percent of women suffering breast tumor. With our understanding that
      BRCAs are Fanconi Anemia (FA) genes, investigations into the FA signaling network
      should provide a previously unrecognized key to unlock in-depth insights into
      both etiology and treatment of breast cancer. Here, we discuss utilization of the
      FA signaling as a unique genetic model system to expand our knowledge about the
      molecular biology of breast cancer and potential applications of the gained
      knowledge to enable preventive and therapeutic approaches for breast cancer
      patient care.

PMID- 30188760
TI  - Distribution of 13-Valent pneumococcal conjugate vaccine serotype streptococcus
      pneumoniae in adults 50 Years and Older presenting with community-acquired
      pneumonia in Israel.
AB  - BACKGROUND: Community acquired pneumonia (CAP) is a major cause of morbidity and
      mortality worldwide, and is a leading cause of hospitalization in previously
      healthy individuals without predisposing risk factors or comorbidities. In this
      study we determined PCV13 serotype distribution in adults aged >=50 years with
      radiographically confirmed CAP in Israel. METHODS: Subjects aged >=50 years were
      enrolled from one of three hospitals (Emek Medical Center, Meir Medical Center
      and Sheba Medical Center) from March 2014 to July 2015. Information was collected
      on subject demographics, comorbidities, risk factors, and pneumococcal vaccine
      immunization status. Subjects presented with suspected CAP supported by
      radiographic evidence, and provided a urine sample and informed consent. Subjects
      without radiographic confirmation of CAP or who received PPSV23 within 30 days of
      study enrollment were excluded from the final analysis. Serotype distribution was
      performed using the urinary antigen detection (UAD) assay and/or microbiological
      culture. RESULTS: Overall, 498 subjects with radiographically confirmed CAP were
      enrolled in the study. Eighty subjects (16.1%) were positive for any S.
      pneumoniae serotype by >=1 assay, and 38 (7.6%) were positive for PCV13 serotypes
      via the UAD. The overall 30-day mortality rate was 1.2%, though S. pneumoniae was
      not isolated from any case leading to death. CONCLUSION: Despite six years of
      high pneumococcal immunization coverage in children in Israel, we have shown that
      7.6% of CAP cases among adults in Israel remain related to PCV13 serotypes; and
      that the burden of PCV13 may be as high as 47% of observed pneumococcal CAP.

PMID- 30188761
TI  - Active natural oil-based nanoemulsion containing tacrolimus for synergistic
      antipsoriatic efficacy.
AB  - AIM: The current study is emphasized on development of a nanoemulsion system that
      simultaneously delivers two antipsoriatic agents viz. Tacrolimus and Kalonji oil
      (functional excepient) topically. MATERIALS & METHODS: A nanoemulsion was
      characterized for quality attributes; a nanoemulsion gel was evaluated for
      spreadability, viscosity, dermal bioavailability, and in vitro efficacy in A-431
      cell line, and so forth. In vivo performance was evaluated on psoriasis model in
      BALB/c mice. RESULTS: Nanoemulsion depicted droplet size: 93.37 +/- 2.58 nm with
      PDI (Polydispersity Index) 0.330 +/- 0.025. The nanoemulsion gel exhibited
      desirable spreadability with sustained release pattern (biphasic). Dermal
      bioavailability enhancement (4.33-fold) accompanied significant in vitro results.
      A significant reduction in serum cytokines and improvement in psoriatic condition
      was achieved in vivo, indicating formulation efficacy compared with marketed
      formulation (Tacroz Forte, Glenmark Pharmaceuticals Ltd, Maharashtra, India).
      CONCLUSION: Nanoemulsion gel thus provides an effective alternative for psoriasis
      treatment.

PMID- 30188765
TI  - 5-Methylcytosine containing CG decamer as Z-DNA embedded sequence for a potential
      Z-DNA binding protein probe.
AB  - Attempting to elucidate biological significance of the left-handed Z-DNA is a
      research challenge due to Z-DNA potential role in many diseases. Discovery of Z
      DNA binding proteins has ignited the interest in search for Z-DNA functions.
      Biosensor with Z-DNA forming probe can be useful to study the interaction between
      Z-DNA conformation and Z-DNA binding proteins. In this study, 5-methylcytosine
      (mC) containing CG decamers were characterized for their suitability to form Z
      DNA and to be used in Z-DNA forming probe. The 5'-thiol oligonucleotide embedded
      with 5'-mCGmCGmCGmCGm CG-3' was designed and developed as a potential Z-DNA
      forming probe for Z-DNA binding protein screening.

PMID- 30188764
TI  - Evaluation of the diagnostic value of emerin and CD56 in papillary thyroid
      carcinoma - an immunohistochemical study.
AB  - Papillary thyroid carcinoma (PTC) is diagnosed in both cytological and
      histological specimens on the basis of distinct nuclear morphology. These
      features may not be prominent in some PTC variants and may be seen in some benign
      conditions. It is necessary to differentiate PTC from other neoplastic and
      nonneoplastic lesions since it affects treatment strategy and patients' fate.
      Emerin is a type II integral membrane protein of the inner nuclear membrane that
      has a characteristic staining pattern in PTC. CD56 is a homophilic membrane
      glycoprotein that is expressed in thyroid follicular epithelial cells and adrenal
      glands. The aim of this study was to evaluate the diagnostic value of emerin
      (positivity, percentage, and highlighting nuclear features) and CD56 (positive
      versus negative) both singly and in combination for differentiation of PTC from
      other neoplastic and nonneoplastic mimics. This study was performed on 50 cases
      of PTC, 9 cases of follicular adenoma (FA), and 12 cases of nonneoplastic thyroid
      lesions using immunohistochemistry for detection of emerin and CD56. Positive
      emerin expression was seen in 82% of PTC and in 16.7% of nonneoplastic cases with
      an absence of expression in FA. CD56 was expressed in 88.9% of FA, 91.7% of
      nonneoplastic cases and in a minority of PTC cases (6%). Positive emerin revealed
      82% sensitivity and 90% specificity, while emerin-highlighted nuclear changes was
      more specific (95%). Negative CD56 expression revealed 84% sensitivity and 90%
      specificity. Combined positive emerin (including highlighting nuclear changes)
      and negative CD56 showed 72% sensitivity and 100% specificity. Positive emerin
      expression (moderate/strong) and its highlighting nuclear changes combined with
      negative CD56 could be a very helpful procedure in difficult and overlapping
      cases with high diagnostic validity (high specificity and positive predictive
      value).

PMID- 30188762
TI  - Tracing the role of plant proteins in the response to metal toxicity: a
      comprehensive review.
AB  - Plants are sessile in nature, but are capable to evade from high level
      concentration of heavy metals like Cd, Hg, Cu, through various metabolic
      pathways. Some of the pathways regulate normal metabolism in plants, whereas
      others are required for for their survival under metal toxicity. Different plant
      proteins act as transporters to transfer metal from one organelle to the other
      and further eliminate it out from the plants. Initially, exposure of heavy
      metals/metalloids to plants lead to over expression of proteins which in turn
      stimulate other stress-related genes. Further, they activate signalling mechanism
      like MAPK cascade, Cd-Calmodulin signalling pathway, and oxidation signalling
      pathway that lead to generation of ROS (reactive oxygen species). Once these ROS
      (highly unstable) are formed, they generate free radicals which react with
      macromolecules like proteins and DNA. This has negative impact on plant growth
      and leads to ageing and, eventually, cell death. The uncontrolled, destructive
      processes damage plants physiologically and ultimately lead to oxidative stress.
      Activation of antioxidant enzymes like SOD (superoxide dismutase) and CAT
      (catalase) allows plants to cope under oxidative stress conditions. Among plant
      proteins, some of the antioxidant enzymes like glutathione, and APX (ascorbate
      peroxidase) play defensive roles against abiotic stress in plants. Chaperones
      help in protein folding to maintain protein stability under stress conditions.
      With this background, the present review gives a brief account of the functions,
      localization and expression pattern of plant proteins against metal/metalloid
      toxicity. Moreover, the aim of this review is also to summarize the cutting edge
      research of plant protein and metal interfaces and their future prospects.

PMID- 30188763
TI  - Suppression of Wnt/beta-catenin signaling by EGF receptor is required for hair
      follicle development.
AB  - Mice that lack the epidermal growth factor receptor (EGFR) fail to develop a hair
      coat, but the mechanism responsible for this deficit is not completely
      understood. Here, we show that EGFR plays a critical role to attenuate wingless
      type MMTV integration site family member (Wnt)/beta-catenin signaling during
      postnatal hair follicle development. Genetic ablation of EGFR in mice resulted in
      increased mitotic activity in matrix cells, apoptosis in hair follicles, and
      impaired differentiation of epithelial lineages that form hair. EGFR is activated
      in wild-type hair follicle stem cells marked with SOX9 or NFATc1 and is essential
      to restrain proliferation and support stem cell numbers and their quiescence. We
      observed elevated levels of Wnt4, 6, 7b, 10a, 10b, and 16 transcripts and
      hyperactivation of the beta-catenin pathway in EGFR knockout follicles. Using
      primary keratinocytes, we linked ligand-induced EGFR activation to suppression of
      nascent mRNA synthesis of Wnt genes. Overexpression of the Wnt antagonist sFRP1
      in mice lacking EGFR demonstrated that elevated Wnts are a major cause for the
      hair follicle defects. Colocalization of transforming growth factor alpha and
      Wnts regulated by EGFR in stem cells and progeny indicates that EGFR autocrine
      loops control Wnts. Our findings define a novel mechanism that integrates EGFR
      and Wnt/beta-catenin pathways to coordinate the delicate balance between
      proliferation and differentiation during development.

PMID- 30188766
TI  - AtrbohD functions downstream of ROP2 and positively regulates waterlogging
      response in Arabidopsis.
AB  - NADPH oxidase AtrbohD plays very important roles in modulating many cellular
      processes through production of signal molecules reactive oxygen species in
      Arabidopsis. However, whether it regulates the response to waterlogging stress is
      unclear. In this report, we showed that expression of AtrbohD was markedly
      induced by waterlogging stress, and mutation in AtrbohD led to clear sensitivity
      of Arabidopsis plants to waterlogging stress. Moreover, waterlogging-promoted
      increases in alcohol dehydrogenase (ADH) activity, ADH1 expression and H2O2
      accumulation were significantly attenuated in two mutant lines of AtrbohD. These
      results indicate that AtrbohD is required for Arabidopsis tolerance to
      waterlogging stress. Besides, GUS staining experiments revealed that disruption
      of small G protein ROP2 encoding gene evidently suppressed the increase of
      AtrbohD expression while defect of AtrbohD did not prominently affect the
      abundance enhancements of ROP2 transcripts under waterlogged conditions.
      Together, these data suggest that AtrbohD functions downstream of ROP2 to
      positively regulate the response to waterlogging stress in Arabidopsis.

PMID- 30188768
TI  - 4D cell biology: big data image analytics and lattice light-sheet imaging reveal
      dynamics of clathrin-mediated endocytosis in stem cell-derived intestinal
      organoids.
AB  - New methods in stem cell 3D organoid tissue culture, advanced imaging, and big
      data image analytics now allow tissue-scale 4D cell biology, but currently
      available analytical pipelines are inadequate for handing and analyzing the
      resulting gigabytes and terabytes of high-content imaging data. We expressed
      fluorescent protein fusions of clathrin and dynamin2 at endogenous levels in
      genome-edited human embryonic stem cells, which were differentiated into hESC
      derived intestinal epithelial organoids. Lattice light-sheet imaging with
      adaptive optics (AO-LLSM) allowed us to image large volumes of these organoids
      (70 * 60 * 40 um xyz) at 5.7 s/frame. We developed an open-source data analysis
      package termed pyLattice to process the resulting large (~60 Gb) movie data sets
      and to track clathrin-mediated endocytosis (CME) events. CME tracks could be
      recorded from ~35 cells at a time, resulting in ~4000 processed tracks per movie.
      On the basis of their localization in the organoid, we classified CME tracks into
      apical, lateral, and basal events and found that CME dynamics is similar for all
      three classes, despite reported differences in membrane tension. pyLattice
      coupled with AO-LLSM makes possible quantitative high temporal and spatial
      resolution analysis of subcellular events within tissues.

PMID- 30188769
TI  - Macrocyclic complexes: synthesis, characterization, antitumor and DNA binding
      studies.
AB  - The present paper deals with the synthesis of novel macrocyclic complexes of the
      type [MLX]X, where [(M = Co(II) (1), and Ni(II) (2) X = (Cl2)]. The complexes are
      synthesized by the reaction of
      ligand(L)diquinolineno[1,3,7,9]tetraazacyclododecine-7,15-ethane(14H,16H)-benzene
      with the corresponding metal salts. The synthesized complexes are thoroughly
      characterized by elemental analysis, FT-IR, 1H-NMR, Mass and electronic spectra.
      The complexes (1) and (2) were evaluated for in vitro cytotoxicity against human
      breast adenocarcinoma cell (MCF-7). MTT cytotoxicity studies shows both the
      complexes are most effective. The binding properties of these complexes with calf
      thymus-DNA were studied by absorption, emission spectra, viscosity measurements,
      and thermal denaturation studies. On binding to CT-DNA, the absorption spectrum
      undergoes bathochromic and hypochromic shifts. The absorption spectral results
      indicate that the intrinsic binding constant (Kb) are 4.8 * 105 M-1 for (1) and
      3.9 * 105 M-1 for (2) respectively, suggesting that complex (1) binds more
      strongly to CT-DNA than complex (2). The viscosity measurement results revealed
      the viscosity of sonicated rod like DNA fragments increased when the complex was
      added to the solution of CT-DNA. The synthesized ligand and its metal complexes
      are screened for antibacterial and antifungal activities.

PMID- 30188767
TI  - Dysfunctional peroxisomes compromise gut structure and host defense by increased
      cell death and Tor-dependent autophagy.
AB  - The gut has a central role in digestion and nutrient absorption, but it also
      serves in defending against pathogens, engages in mutually beneficial
      interactions with commensals, and is a major source of endocrine signals. Gut
      homeostasis is necessary for organismal health and changes to the gut are
      associated with conditions like obesity and diabetes and inflammatory illnesses
      like Crohn's disease. We report that peroxisomes, organelles involved in lipid
      metabolism and redox balance, are required to maintain gut epithelium homeostasis
      and renewal in Drosophila and for survival and development of the organism.
      Dysfunctional peroxisomes in gut epithelial cells activate Tor kinase-dependent
      autophagy that increases cell death and epithelial instability, which ultimately
      alter the composition of the intestinal microbiota, compromise immune pathways in
      the gut in response to infection, and affect organismal survival. Peroxisomes in
      the gut effectively function as hubs that coordinate responses from stress,
      metabolic, and immune signaling pathways to maintain enteric health and the
      functionality of the gut-microbe interface.

PMID- 30188770
TI  - Effects of exogenously-applied L-ascorbic acid on root expansive growth and
      viability of the border-like cells.
AB  - Functions of exogenous L-ascorbic acid in plant roots are poorly understood.
      Recent study by Makavitskaya et al. (doi.org/10.1093/jxb/ery056) has demonstrated
      that exogenous ascorbate can be released from roots in response to salt stress,
      and can trigger elevation in the cytosolic free Ca2+. Here, we report that
      exogenous ascorbate significantly modifies root elongation in Arabidopsis
      thaliana. Using a medium exchange technique, we have shown that 10-100 uM
      ascorbate induces small but significant increase in root elongation while higher
      levels cause its dramatic decrease. Root border cells of Pisum sativum have been
      losing viability twice faster in the presence of ascorbate that under control
      conditions, as tested by the confocal microscopy and a combined staining with
      propidium iodide and fluorescein diacetate.

PMID- 30188772
TI  - Synthesis of cyclobutane nucleoside analogues 3: Preparation of carbocyclic
      derivatives of oxetanocin.
AB  - A synthesis of cyclobutene nucleoside analogs in which the nucleobase is tethered
      by a methylene group is described. The coupling of 6-chloropurine with 3
      hydroxymethyl-cyclobutanone proceeds via its triflate to give both N-7 and N-9
      regioisomers with relative yields corresponding to the calculated charge
      distribution of the 6-chloropurinyl anion. The stereoselective reduction of the N
      alkylated ketones yielded quantitatively one stereoisomer in each case. The
      structural assignments were based on spectroscopic data and single crystal X-ray
      diffraction. Attempts to photoexcite the N-7 and N-9 ketones in order to promote
      ring-expansion did not ensue. Preliminary evidence suggests a
      photodecarbonylation to cyclopropanes took place.

PMID- 30188773
TI  - Comparative Effectiveness of Generic Latanoprost Versus Branded Prostaglandin
      Analogs for Primary Open Angle Glaucoma.
AB  - PURPOSE: The purpose of the study is to determine the comparative effectiveness
      of generic latanoprost (GL) to its branded (BL) counterpart and other brand-name
      prostaglandin analogs (bPGAs) in preventing the need for additional therapy in
      the treatment of primary open angle glaucoma (POAG). METHODS: Retrospective
      cohort study using US commercial medical claims data. All new POAG patients from
      2000 to 2015 who initiated treatment with either GL or BL were included.
      Exclusion occurred for having less than 2 years of time in the plan prior to
      diagnosis, previous use of glaucoma medications, or any diagnosis of glaucoma
      other than POAG at any time. Analyses compared GL to BL and also to those who
      received any branded PGA after 2011 (when the generic became available). Cox
      proportional hazard regression was used to assess the hazards of filling a
      prescription for a second IOP-lowering medication or having surgical
      intervention, individually and either outcome combined. RESULTS: A total of 6317
      and 4150 POAG patients were treated with GL and BL, respectively. After 2010,
      6317 GL and 3703 brand-name prostaglandin analog (bPGA) POAG patients met
      criteria for inclusion. After adjustment, compared to BL, the GL conferred a
      reduced hazard of having a glaucoma procedure performed (hazard ratio [HR] =
      0.72, 95% CI: 0.62-0.84, p < 0.001) and the combined outcome (HR = 0.90, 95% CI:
      0.83-0.97, p = 0.006) but was not associated with having a second IOP medication
      (HR = 0.95, 95% CI: 0.87-1.03, p = 0.18). Compared to the bPGAs, however, GL
      conferred a reduced hazard in each comparison (second IOP medication HR = 0.87,
      95% CI: 0.81-0.94, p < 0.001; surgery HR = 0.70, 95% CI: 0.61-0.81, p < 0.001;
      combined HR = 0.85, 95% CI: 0.79-0.92, p < 0.001). Sensitivity analyses confirmed
      these findings. CONCLUSIONS: GL was no less and possibly more effective in
      preventing the need for additional intervention than branded PGAs.

PMID- 30188771
TI  - Neutrophils as sources of dinucleotide polyphosphates and metabolism by
      epithelial ENPP1 to influence barrier function via adenosine signaling.
AB  - Extracellular adenosine signaling is established as a protective component in
      mucosal inflammatory responses. The sources of extracellular adenosine include
      enzymatic processing from nucleotides, such as ATP and AMP, that can be liberated
      from a variety of cell types, including infiltrating leukocytes. Here we
      demonstrate that activated human neutrophils are a source of diadenosine
      triphosphate (Ap3A), providing an additional source of nucleotides during
      inflammation. Profiling murine enteroids and intestinal epithelial cell lines
      revealed that intestinal epithelia prominently express apical and lateral
      ectonucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1), a member of the ENPP
      family of enzymes that metabolize diadenosine phosphates, especially Ap3A.
      Extensions of these studies demonstrated that intestinal epithelia metabolize
      Ap3A to ADP and AMP, which are further metabolized to adenosine and made
      available to activate surface adenosine receptors. Using loss and gain of ENPP1
      approaches, we revealed that ENPP1 coordinates epithelial barrier formation and
      promotes epithelial wound healing responses. These studies demonstrate the
      cooperative metabolism between Ap3A and ENPP1 function to provide a significant
      source of adenosine, subserving its role in inflammatory resolution.

PMID- 30188774
TI  - Cargo induces retromer-mediated membrane remodeling on membranes.
AB  - Endosomes serve as a central sorting station of lipids and proteins that arrive
      via vesicular carrier from the plasma membrane and the Golgi complex. At the
      endosome, retromer complexes sort selected receptors and membrane proteins into
      tubules or vesicles that bud off the endosome. The mature endosome finally fuses
      with the lysosome. Retromer complexes consist of a cargo selection complex (CSC)
      and a membrane remodeling part (sorting nexin [SNX]-Bin/amphiphysin/Rvs [BAR], or
      Snx3 in yeast) and different assemblies of retromer mediate recycling of
      different cargoes. Due to this complexity, the exact order of events that results
      in carrier formation is not yet understood. Here, we reconstituted this process
      on giant unilamellar vesicles together with purified retromer complexes from
      yeast and selected cargoes. Our data reveal that the membrane remodeling activity
      of both Snx3 and the SNX-BAR complex is strongly reduced at low concentrations,
      which can be reactivated by CSC. At even lower concentrations, these complexes
      still associate with membranes, but only remodel membranes in the presence of
      their specific cargoes. Our data thus favor a simple model, where cargo functions
      as a specific trigger of retromer-mediated sorting on endosomes.

PMID- 30188775
TI  - Cytokinin-overinduced transcription factors and thalianol cluster genes in
      CARBOXYL-TERMINAL DOMAIN PHOSPHATASE-LIKE 4-silenced Arabidopsis roots during de
      novo shoot organogenesis.
AB  - Cytokinin (CK) is one of key phytohormones for de-differentiation and de novo
      organogenesis in plants. During the CK-mediated organogenesis not only genes in
      CK homeostasis, perception and signal transduction, but also factors regulating
      basic transcription, splicing and chromatin remodeling contribute to coordinate a
      sequence of events leading to formation of new organs. We have found that
      silencing of RNA polymerase II CTD-phosohatase-like 4 (CPL4RNAi) in Arabidopsis
      induces CK-oversensitive de novo shoot organogenesis (DNSO) from roots, partly by
      early activation of transcription factors such as WUSCHEL and SHOOT MERISTEMLESS
      during pre-incubation on callus induction media. Here we show that a cluster of
      thalianol-biogenesis genes is highly expressed in the CPL4RNAi during DNSO,
      implying involvement of CPL4 in transcriptional regulation of the thalianol
      pathway in DNSO.

PMID- 30188777
TI  - The Hippocampus Promotes Effective Saccadic Information Gathering in Humans.
AB  - It is well established that the hippocampus is critical for memory. Recent
      evidence suggests that one function of hippocampal memory processing is to
      optimize how people actively explore the world. Here we demonstrate that the link
      between the hippocampus and exploration extends even to the moment-to-moment use
      of eye movements during visuospatial memory encoding. In Experiment 1, we
      examined relationships between study-phase eye movements in healthy individuals
      and subsequent performance on a spatial reconstruction test. In addition to
      quantitative measures of viewing behaviors (e.g., how many fixations or saccades
      were deployed during study), we used the information-theoretical measure of
      entropy to assess the amount of randomness or disorganization in participants'
      scanning behaviors. We found that the use of scanpaths during study that were
      lower in entropy (e.g., more organized, less random) predicted more accurate
      spatial reconstruction both within and between participants. Scanpath entropy was
      a better predictor of reconstruction accuracy than were the quantitative measures
      of viewing. In Experiment 2, we found that individuals with hippocampal amnesia
      tended to engage in viewing patterns that were higher in entropy (less organized)
      relative to healthy comparisons. These findings reveal a critical role of the
      hippocampus in guiding eye movement exploration to optimize visuospatial
      relational memory.

PMID- 30188776
TI  - Use of hafnium(IV) oxide in biosensors.
AB  - Hafnium(IV) oxide is a material with properties that can increase the
      sensitivity, durability, and reliability of biosensors made from silicon dioxide
      and other semiconductor materials due to its high dielectric constant,
      thermodynamic stability, and the simplicity with which it can be deposited. This
      work describes the use of this material in biosensors based on field-effect
      transistors to detect ions and DNA, in immunosensors to detect an antigen
      antibody complex, its use as a contrast material in computed tomography scans and
      the possibility of using it in optic biosensors in the infrared region. Its low
      cost and versatility in the field of biosensors is underscored.

PMID- 30188779
TI  - Increased Neural Strength and Reliability to Audiovisual Stimuli at the Boundary
      of Peripersonal Space.
AB  - The actionable space surrounding the body, referred to as peripersonal space
      (PPS), has been the subject of significant interest of late within the broader
      framework of embodied cognition. Neurophysiological and neuroimaging studies have
      shown the representation of PPS to be built from visuotactile and audiotactile
      neurons within a frontoparietal network and whose activity is modulated by the
      presence of stimuli in proximity to the body. In contrast to single-unit and fMRI
      studies, an area of inquiry that has received little attention is the EEG
      characterization associated with PPS processing. Furthermore, although PPS is
      encoded by multisensory neurons, to date, there has been no EEG study
      systematically examining neural responses to unisensory and multisensory stimuli,
      as these are presented outside, near, and within the boundary of PPS. Similarly,
      it remains poorly understood whether multisensory integration is generally more
      likely at certain spatial locations (e.g., near the body) or whether the cross
      modal tactile facilitation that occurs within PPS is simply due to a reduction in
      the distance between sensory stimuli when close to the body and in line with the
      spatial principle of multisensory integration. In the current study, to examine
      the neural dynamics of multisensory processing within and beyond the PPS
      boundary, we present auditory, visual, and audiovisual stimuli at various
      distances relative to participants' reaching limit-an approximation of PPS-while
      recording continuous high-density EEG. We question whether multisensory (vs.
      unisensory) processing varies as a function of stimulus-observer distance.
      Results demonstrate a significant increase of global field power (i.e., overall
      strength of response across the entire electrode montage) for stimuli presented
      at the PPS boundary-an increase that is largest under multisensory (i.e.,
      audiovisual) conditions. Source localization of the major contributors to this
      global field power difference suggests neural generators in the intraparietal
      sulcus and insular cortex, hubs for visuotactile and audiotactile PPS processing.
      Furthermore, when neural dynamics are examined in more detail, changes in the
      reliability of evoked potentials in centroparietal electrodes are predictive on a
      subject-by-subject basis of the later changes in estimated current strength at
      the intraparietal sulcus linked to stimulus proximity to the PPS boundary.
      Together, these results provide a previously unrealized view into the neural
      dynamics and temporal code associated with the encoding of nontactile
      multisensory around the PPS boundary.

PMID- 30188778
TI  - Categorization Goals Modulate the Use of Natural Scene Statistics.
AB  - Understanding natural scenes involves the contribution of bottom-up analysis and
      top-down modulatory processes. However, the interaction of these processes during
      the categorization of natural scenes is not well understood. In the current
      study, we approached this issue using ERPs and behavioral and computational data.
      We presented pictures of natural scenes and asked participants to categorize them
      in response to different questions (Is it an animal/vehicle? Is it
      indoors/outdoors? Are there one/two foreground elements?). ERPs for target scenes
      requiring a "yes" response began to differ from those of nontarget scenes,
      beginning at 250 msec from picture onset, and this ERP difference was unmodulated
      by the categorization questions. Earlier ERPs showed category-specific
      differences (e.g., between animals and vehicles), which were associated with the
      processing of scene statistics. From 180 msec after scene onset, these category
      specific ERP differences were modulated by the categorization question that was
      asked. Categorization goals do not modulate only later stages associated with
      target/nontarget decision but also earlier perceptual stages, which are involved
      in the processing of scene statistics.

PMID- 30188780
TI  - Spatial Frequency Tolerant Visual Object Representations in the Human Ventral and
      Dorsal Visual Processing Pathways.
AB  - Primate ventral and dorsal visual pathways both contain visual object
      representations. Dorsal regions receive direct input from magnocellular layers of
      LGN while ventral regions receive directly input from both magnocellular and
      parvocellular layers of LGN. Because magnocellular layers prefer low SF and
      parvocellular layers prefer mid- to high-SF components of the image, object
      representations in ventral and dorsal regions may differ in how they represent
      visual input from different spatial scales. To test this prediction, we asked
      observers to view blocks of images from six object categories shown in full
      spectrum, high SF, or low SF. We found robust object category decoding in all SF
      conditions as well as SF decoding in nearly all the early visual, ventral, and
      dorsal regions examined. Cross-SF decoding further revealed that object category
      representations in all regions exhibited substantial tolerance across the SF
      components. No difference between ventral and dorsal regions was found in their
      preference for the different SF components. Further comparisons revealed that,
      whereas differences in the SF component separated object category representations
      in early visual areas, such a separation was much smaller in downstream ventral
      and dorsal regions. In those regions, variations among the object categories
      played a more significant role in shaping the visual representational structures.
      Our findings show that ventral and dorsal regions are similar in how they
      represent visual input from different spatial scales and argue against a
      dissociation of these regions based on differential sensitivity to different SFs.

PMID- 30188781
TI  - Occupational physical activity in brewery and office workers.
AB  - Active lifestyles are beneficial to health and well-being but our workplaces may
      not be inherently supportive of physical activity at work. With the increasing
      use of technology in the workplace, many jobs are becoming more sedentary. The
      purpose of this study was to characterize levels of occupational physical
      activity (OPA) among active and sedentary workers. Two types of activity trackers
      (Fitbit Charge HR and Hexoskin) were used to assess activity measures (steps,
      heart rate, and energy expenditure) among workers during one full work shift. The
      first objective of the study was to assess the agreement between two types of
      accelerometer-based activity trackers as measures of occupational physical
      activity. The second objective of this study was to assess differences in
      measures of OPA among workers in generally physically active (brewery) and
      sedentary (office) work environments. Occupational physical activity data were
      collected from 50 workers in beer-brewing tasks and 51 workers in office work
      tasks. The 101 subjects were from the brewing service sector, a call center, and
      an engineering office within a manufacturing facility. A two-factor repeated
      measures analysis of variance (ANOVA) was used to assess the two activity
      tracking devices while two-sample t-tests were used to compare the two worker
      groups. There were statistically significant differences in total steps and mean
      heart rate between the two devices. When comparing the two groups of workers
      there were statistically significant differences in measures of steps, mean heart
      rate, and energy expenditure. The results of the present study provide
      quantitative evidence that levels of OPA should be identified for different work
      groups.

PMID- 30188783
TI  - Low-Fat Abiraterone Food Effect Is of Great Consequence.

PMID- 30188784
TI  - Reply to I.F. Tannock, P. Isaacsson Velho et al, M. Tiako Meyo et al, and
      F.J.S.H. Woei-A-Jin et al.

PMID- 30188782
TI  - Engaging parents around vaccine confidence: proceedings from the National HPV
      Vaccination Roundtable meetings.
AB  - HPV vaccine uptake remains below national goals in the US, driven in part by
      parental uncertainty about the vaccine fueled by negative stories on social media
      and other information platforms. To identify opportunities for mobilizing parents
      to increase HPV vaccination uptake, the National HPV Vaccination Roundtable and
      Vaccinate Adolescents Against Cancers program convened two national meetings in
      2016 at the American Cancer Society. Stakeholders recommended a focus on positive
      message to parents; cultivating parent champions to use the power of personal
      storytelling and to distribute these messages; and defining the role of national
      organizations in supporting parent champions. Stakeholders supported three
      message themes: HPV vaccination is the norm, HPV vaccination is cancer
      prevention, and HPV vaccination supports families across generations. Parents'
      negative stories about vaccination are especially difficult to counteract with
      scientific evidence, making the cultivation of pro-vaccine parent champions an
      especially promising intervention on social media and other information
      platforms.

PMID- 30188785
TI  - Low-Dose Abiraterone With Food: Rebutting an Editorial.

PMID- 30188786
TI  - Human Papillomavirus Testing in Head and Neck Carcinomas: ASCO Clinical Practice
      Guideline Endorsement of the College of American Pathologists Guideline.
AB  - Purpose The College of American Pathologists produced an evidence-based guideline
      on testing, application, interpretation, and reporting of human papillomavirus
      (HPV) and surrogate marker tests in head and neck carcinomas that was determined
      to be relevant to the American Society of Clinical Oncology (ASCO) membership.
      Methods The College of American Pathologists HPV Testing in Head and Neck
      Carcinomas guideline was reviewed by ASCO content experts for clinical accuracy
      and by methodologists for developmental rigor. On favorable review, an ASCO
      Expert Panel was convened to review the guideline contents and recommendations.
      Results The ASCO Expert Panel determined that the recommendations from the HPV
      Testing in Head and Neck Carcinomas guideline, published in 2018, are clear,
      thorough, and based upon the most relevant scientific evidence. ASCO endorsed the
      guideline and added minor qualifying statements. Recommendations It is
      recommended that HPV tumor status should be determined for newly diagnosed
      oropharyngeal squamous cell carcinomas. HPV tumor status testing may be performed
      by surrogate marker p16 immunohistochemistry either on the primary tumor or from
      cervical nodal metastases only if an oropharyngeal primary tumor is present. The
      threshold for positivity is at least 70% nuclear and cytoplasmic expression with
      at least moderate to strong intensity. Additional confirmatory testing may be
      done at the discretion of the pathologist and/or treating clinician. Pathologists
      should not routinely determine HPV tumor status in nonsquamous carcinomas of the
      oropharynx or non-oropharyngeal squamous cell carcinomas of the head and neck.
      When there is uncertainty of histologic type or whether a poorly differentiated
      oropharyngeal tumor is nonsquamous, HPV tumor status testing may be warranted and
      at the discretion of the pathologist and/or treating clinician. Additional
      information is available at: www.asco.org/head-neck-cancer-guidelines .

PMID- 30188787
TI  - There Is Now Compelling Evidence to Further Evaluate Lower Doses of Abiraterone
      Acetate in Men With Metastatic Prostate Cancer: It Should Be Safer, May Be as
      Effective and Less Expensive.

PMID- 30188788
TI  - Low-Dose Abiraterone Regimen: Drug Monitoring Might Be the Key.

PMID- 30188790
TI  - Dose Reduction May Jeopardize Efficacy of Abiraterone Acetate.

PMID- 30188791
TI  - Reply to I.F. Tannock, P. Isaacsson Velho et al, R.Z. Szmulewitz et al, M. Tiako
      Meyo et al, and F.J.S.H. Woei-A-Jin et al.

PMID- 30188789
TI  - High-Dose Chemotherapy and Blood Autologous Stem-Cell Rescue Compared With
      Standard Chemotherapy in Localized High-Risk Ewing Sarcoma: Results of Euro
      E.W.I.N.G.99 and Ewing-2008.
AB  - Purpose For over 30 years, the place of consolidation high-dose chemotherapy in
      Ewing sarcoma (ES) has been controversial. A randomized study was conducted to
      determine whether consolidation high-dose chemotherapy improved survival in
      patients with localized ES at high risk for relapse. Methods Randomization
      between busulfan and melphalan (BuMel) or standard chemotherapy (vincristine,
      dactinomycin, and ifosfamide [VAI], seven courses) was offered to patients if
      they were younger than 50 years of age with poor histologic response (>= 10%
      viable cells) after receiving vincristine, ifosfamide, doxorubicin, and etoposide
      (six courses); or had a tumor volume at diagnosis >= 200 mL if unresected, or
      initially resected, or resected after radiotherapy. A 15% improvement in 3-year
      event-free survival (EFS) was sought (hazard ratio [HR], 0.60). Results Between
      2000 and 2015, 240 patients classified as high risk (median age, 17.1 years) were
      randomly assigned to VAI (n = 118) or BuMel (n = 122). Seventy-eight percent
      entered the trial because of poor histologic response after chemotherapy alone.
      Median follow-up was 7.8 years. In an intent-to-treat analysis, the risk of event
      was significantly decreased by BuMel compared with VAI: HR, 0.64 (95% CI, 0.43 to
      0.95; P = .026); 3- and 8-year EFS were, respectively, 69.0% (95% CI, 60.2% to
      76.6%) versus 56.7% (95% CI, 47.6% to 65.4%) and 60.7% (95% CI, 51.1% to 69.6%)
      versus 47.1% (95% CI, 37.7% to 56.8%). Overall survival (OS) also favored BuMel:
      HR, 0.63 (95% CI, 0.41 to 0.95; P = .028); 3- and 8-year OS were, respectively,
      78.0% (95% CI, 69.6% to 84.5%) versus 72.2% (95% CI, 63.3% to 79.6%) and 64.5%
      (95% CI, 54.4% to 73.5%) versus 55.6% (95% CI, 45.8% to 65.1%). Results were
      consistent in the sensitivity analysis. Two patients died as a result of BuMel
      related toxicity, one after standard chemotherapy. Significantly more BuMel
      patients experienced severe acute toxicities from this course of chemotherapy
      compared with multiple VAI courses. Conclusion BuMel improved EFS and OS when
      given after vincristine, ifosfamide, doxorubicin, and etoposide induction in
      localized ES with predefined high-risk factors. For this group of patients, BuMel
      may be an important addition to the standard of care.

PMID- 30188793
TI  - The spatial pattern of methacholine bronchoconstriction recurs when supine,
      independently of posture during provocation, but does not recur between postures.
AB  - The location of lung regions with compromised ventilation (often called
      ventilation defects) during a bronchoconstriction event may be influenced by
      posture. We aimed to determine the effect of prone vs. supine posture on the
      spatial pattern of methacholine-induced bronchoconstriction in six healthy adults
      (ages 21-41, three females) using specific ventilation imaging. Three postural
      conditions were chosen to assign the effect of posture to the drug administration
      and/or imaging phase of the experiment - supine methacholine administration
      followed by supine imaging, prone methacholine administration followed by supine
      imaging, and prone methacholine administration followed by prone imaging. The two
      conditions in which imaging was performed supine had similar spatial patterns of
      bronchoconstriction despite a change in posture during methacholine
      administration; the odds ratio for recurrent constriction was mean (SD) = 7.4
      (3.9). Conversely, dissimilar spatial patterns of bronchoconstriction emerged
      when posture during imaging was changed; the odds ratio for recurrent
      constriction between the prone methacholine/supine imaging condition and the
      prone methacholine/prone imaging condition was 1.2 (0.9). Logistic regression
      showed that height above the dependent lung border was a significant negative
      predictor of constriction in the two supine imaging conditions (p<0.001 for
      each), but not in the prone imaging condition (p=0.20). These results show that
      the spatial pattern of methacholine bronchoconstriction is recurrent in the
      supine posture, regardless of whether methacholine is given prone or supine, but
      that prone posture during imaging eliminates that recurrent pattern and reduces
      its dependence on gravitational height.

PMID- 30188792
TI  - Vesicular trafficking plays a role in centriole disengagement and duplication.
AB  - Centrosomes are the major microtubule-nucleating and microtubule-organizing
      centers of cells and play crucial roles in microtubule anchoring, organelle
      positioning, and ciliogenesis. At the centrosome core lies a tightly associated
      or "engaged" mother-daughter centriole pair.  During mitotic exit, removal of
      centrosomal proteins pericentrin and Cep215 promotes "disengagement" by the
      dissolution of intercentriolar linkers, ensuring a single centriole duplication
      event per cell cycle.  Herein, we explore a new mechanism involving vesicular
      trafficking for the removal of centrosomal Cep215. Using small interfering RNA
      and CRISPR/Cas9 gene-edited cells, we show that the endocytic protein EHD1
      regulates Cep215 transport from centrosomes to the spindle midbody, thus
      facilitating disengagement and duplication. We demonstrate that EHD1 and Cep215
      interact and show that Cep215 displays increased localization to vesicles
      containing EHD1 during mitosis. Moreover, Cep215-containing vesicles are positive
      for internalized transferrin, demonstrating their endocytic origin. Thus, we
      describe a novel relationship between endocytic trafficking and the centrosome
      cycle, whereby vesicles of endocytic origin are used to remove key regulatory
      proteins from centrosomes to control centriole duplication.

PMID- 30188794
TI  - EFFECTS OF MODEST IRON LOADING ON IRON INDICES IN HEALTHY INDIVIDUALS.
AB  - Intravenous (iv) iron administration is typically indicated in individuals who
      have iron deficiency refractory to oral iron. However, in certain chronic disease
      states, it may be beneficial to administer iv iron to individuals who are not
      strictly iron deficient. The purpose of this study was to define a dose-response
      relationship between clinical indices of iron status and modest loading with iv
      iron in healthy, iron-replete participants. This was a double-blind, controlled
      study involving 18 male participants. Participants were block randomised 2:1 to
      the iron and saline (control) groups. Participants in the iron group received 250
      mg of iv iron, once a month for six months, provided that their ferritin remained
      < 300 ug/L and their transferrin saturation remained < 45%. Otherwise they
      received a saline infusion, as did the control participants. Iron indices were
      measured monthly during the study. The pulmonary vascular response to sustained
      hypoxia and total hemoglobin mass were measured before, at three months
      (hemoglobin mass only) and at six months, as variables that may be affected by
      iron loading. Serum ferritin was robustly elevated by iv iron by 0.21 ug/L/mg of
      iron delivered (95% CI: 0.15-0.26 ug/L/mg), but the effects on all other iron
      indices did not reach statistical significance. The pulmonary vascular response
      to sustained hypoxia was significantly suppressed by iron loading at six months,
      but the hemoglobin mass was unaffected. We conclude that the robust effect on
      ferritin provides a quantitative measure for the degree of iron loading in iron
      replete individuals.

PMID- 30188795
TI  - Dysfunction of the Systemic Right Ventricle After Atrial Switch: Physiological
      Implications of Altered Septal Geometry and Load.
AB  - Atrial switch operation in patients with transposition of the great arteries
      (TGA), leads to leftward shift and changes the geometry of the interventricular
      septum. By including the implications of regional work and septal curvature, this
      study investigates if changes in septal function and geometry contribute to
      reduced function of the systemic right ventricle (RV) in adult TGA patients.
      Regional myocardial work estimation has been possible by applying a recently
      developed method for non-invasive work calculation based on echocardiography. In
      14 TGA patients (32+/-6 years, mean+/-SD) and 14 healthy controls, systemic
      ventricular systolic strains were measured by speckle tracking echocardiography
      and regional work was calculated by pressure-strain analysis. In TGA patients
      septal longitudinal strain was reduced to -14+/-2% vs -20+/-2% in controls
      (p<0.01) and septal work was reduced from 2046+/-318 to 1146+/-260 mmHg*%
      (p<0.01). Septal circumferential strain measured in a subgroup of patients, was
      reduced to -11+/-3% vs. -27+/-3% in controls (p<0.01), and a reduction of septal
      work (540+/-273 vs 2663+/-459 mmHg*%) were seen (p<0.01). These reductions were
      in part attributed to elevated afterload due to increased radius of curvature of
      the leftward shifted septum. To conclude, in this mechanistic study we
      demonstrate that septal dysfunction contributes to failure of the systemic RV
      after atrial switch in TGA patients. This is potentially a long-term response to
      increased afterload due to a flatter septum and suggests that medical therapy
      that counteracts septal flattening may improve function of the systemic RV.

PMID- 30188796
TI  - Relationship between cerebral blood flow estimated by transcranial Doppler
      ultrasound and single photon emission computed tomography in elderly with
      dementia.
AB  - Transcranial Doppler (TCD) ultrasonography is a non-invasive technique allowing
      continuous recording of cerebral blood flow (CBF) velocity. However, it is
      unclear whether the CBF estimated by TCD would be reliable for the comparison
      between individuals. The present study aimed to clarify the relationship between
      middle cerebral artery blood flow (MCA BF) measured by TCD and regional and total
      CBF measured by single photon emission computed tomography (SPECT-CBF) with a
      quantification software program, 3-dimensional stereotaxic region of interest
      template. We recruited 91 elderly subjects with and without dementia. MCA blood
      flow velocity (MCA V) and middle cerebral artery cross-sectional area (AM) were
      measured by TCD and magnetic resonance angiography, respectively. MCA BF was
      calculated by the product of MCA V and AM. Diastolic or mean MCA V and MCA BF
      were significantly correlated with SPECT-CBF in several segments. Interestingly,
      the correlation coefficient in temporal segment of SPECT-CBF was higher than
      those of the other segments. Moreover, correlations between MCA BF and SPECT-CBF
      were stronger as compared with those between MCA V and SPECT-CBF. These findings
      suggest that both mean MCA V and MCA BF with TCD ultrasonography would be useful
      for CBF comparison between individuals especially in temporal region although
      estimated blood flow with arterial area seems to be better than using simple flow
      velocity.

PMID- 30188797
TI  - Time course of inter-limb strength transfer after unilateral handgrip training.
AB  - 'Cross-education' is the increase in strength or functional performance of an
      untrained limb after unilateral training. A major limitation for clinical
      translation from unilateral injury includes knowledge on the minimum time for the
      emergence of crossed effects. Therefore, the primary purpose was to characterize
      the time-course of bilateral strength changes during both 'traditional' (n=11)
      and 'daily' (n=8) unilateral handgrip training in neurologically intact
      participants. 'Traditional' training included 5 sets of 5 maximal voluntary
      handgrip contractions 3x/week for 6-weeks whereas 'daily' training included the
      same number of sessions and contractions but over 18 consecutive days. Three pre-
      and one post-test session evaluated strength, muscle activation, and reflex
      excitability bilaterally. Time course information was assessed by recording
      handgrip force for every contraction in the trained limb and from a single
      contraction on every third training session in the untrained limb. 6 weeks of
      'traditional' training increased handgrip strength in the trained limb after the
      9th session while the untrained limb was stronger after the 12th session. This
      was accompanied by increased peak muscle activation and bilateral alterations in
      Hoffmann (H-) reflex excitability. 'Daily' training revealed a similar number of
      sessions (15) were required to induce significant strength gains in the untrained
      limb (7.8% compared to 12.5%) in approximately half the duration of 'traditional'
      training. Therefore, minimizing rest days may improve the efficiency of
      unilateral training when the trained limb is not the focus. Establishing a 'dose'
      for the time-course of adaptation to strength training is paramount for effective
      translation to rehabilitative interventions.

PMID- 30188798
TI  - Effects of Testosterone and Progressive Resistance Exercise on Vascular Function
      in Older Men.
AB  - The cardiovascular effects of testosterone (T) are controversial. Low T has been
      associated with accelerated vascular aging, characterized by large elastic artery
      stiffening (decreased compliance), intimal-medial thickening (IMT), and
      endothelial dysfunction. Endurance exercise improves vascular function, but
      resistance training may increase arterial stiffness. We sought to determine
      whether T supplementation improved markers of vascular aging in men with low
      normal T, and whether T supplementation prevented arterial stiffness with
      resistance exercise. We studied 160 community dwelling older men (66 +/- 5 years)
      with low-normal baseline total T levels (200-350 ng/dL). Participants were
      randomized to transdermal T gel targeting either a lower [400-550 ng/dL] or
      higher [600-1000 ng/dL] T range or to placebo gel, and to either progressive
      resistance training (PRT) or to no exercise for 12 months. Carotid artery
      stiffness (arterial compliance) and carotid IMT were measured at baseline, 6, and
      12 months. Endothelial function (brachial artery flow-mediated dilation) was
      measured in a subset (N=86). Changes in carotid artery compliance, IMT and
      endothelial function with either the lower or higher range of T supplementation
      were not different from placebo at 6 or 12 months. There were no differences
      between PRT and no PRT groups, alone or with T supplementation, in changes in any
      of the vascular measures at either time point. Supplementation of T and PRT in
      older men with low-normal levels do not appear to improve or harm vascular
      function.

PMID- 30188799
TI  - Charting the human respiratory tract with airborne nanoparticles - evaluation of
      the Airspace Dimension Assessment technique.
AB  - Airspace Dimension Assessment (AiDA) is a technique to assess lung morphology by
      measuring lung deposition of inhaled nanoparticles. Nanoparticles deposit in the
      lungs predominately by diffusion and average diffusion distances, corresponding
      to effective airspace radii, rAiDA, can be inferred from measurements of particle
      recovery, after varied breath-holds. Also, particle recovery after a zero second
      breath-hold, R0, may hold information about the small conducting airways. This
      study investigates rAiDA at different volumetric sample depths in the lungs of
      healthy subjects. Measurements were performed with 50 nm polystyrene nanospheres
      on 19 healthy subjects aged 17-67 yrs. Volumetric sample depths ranged from 200
      to 5000 mL and breath-hold times from 5 to 20 s. At the examined volumetric
      sample depths, rAiDA values ranged from approximately 200-600 MUm, which
      correspond to dimensions of the bronchiolar and the gas-exchanging regions of the
      lungs. R0 decreased with volumetric sample depth and showed more inter-subject
      variation than rAiDA. Correlations were found between the AiDA parameters,
      anthropometry and lung function tests, but not between rAiDA and R0. For repeated
      measurements on three subjects over an 18 months period, rAiDA varied on average
      within +/- 7 MUm (+/- 2.4 %). The results indicate that AiDA has potential as an
      efficient new in vivo technique to assess individual lung properties. The
      information obtained by such measurements may be of value for lung diagnostics,
      especially for the distal lungs, which are challenging to examine directly by
      other means.

PMID- 30188800
TI  - SIMPLE INTERMITTENT RESISTANCE ACTIVITY MITIGATES THE DETRIMENTAL EFFECT OF
      PROLONGED UNBROKEN SITTING ON ARTERIAL FUNCTION IN OVERWEIGHT AND OBESE ADULTS.
AB  - Prolonged sitting contributes to cardiovascular disease (CVD) risk. The
      underlying mechanisms are unknown, but may include changes in arterial function
      and vasoactive mediators. We examined the effects of prolonged unbroken sitting,
      relative to regular active interruptions to sitting time, on arterial function in
      adults at increased CVD risk. In a randomized crossover trial, 19 sedentary
      overweight/obese adults (mean+/-SD 57+/-12 yrs), completed two laboratory-based
      conditions: five hours uninterrupted sitting (SIT) and; five hours sitting
      interrupted every 30 minutes by three minutes of simple resistance activities
      (SRA). Femoral artery function (flow mediated dilation; FMD), blood flow and
      shear rate were measured at zero hour, 30 minutes, one, two and five hours.
      Brachial FMD was assessed at zero and five hours. Plasma was collected hourly for
      measurement of endothelin-1 (ET-1), nitrates/nitrites, vascular cell adhesion
      molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1). There was a
      significant decline in femoral artery FMD, averaged over five hours in the SIT
      condition, relative to SRA (p<0.001). Plasma ET-1 total AUC over five hours
      increased in the SIT condition compared to SRA (p=0.006). There was no
      significant difference between conditions in femoral or brachial shear rate,
      brachial FMD, nitrates/nitrites, VCAM-1 or ICAM-1 (p>0.05 for all). Five hours of
      prolonged sitting, relative to regular interruptions to sitting time, impaired
      femoral artery vasodilator function and increased circulating ET-1 in
      overweight/obese adults. There is the need to build on this evidence beyond acute
      observations to better understand the potential longer-term vascular-related
      consequences of prolonged sitting.

PMID- 30188801
TI  - Regulation of Regional Cerebral Blood Flow During Graded Reflex-Mediated
      Sympathetic Activation via Lower Body Negative Pressure.
AB  - The role of the sympathetic nervous system in cerebral blood flow (CBF)
      regulation remains unclear. Previous studies have primarily measured middle
      cerebral artery blood velocity to assess CBF. Recently, there has been a
      transition towards measuring internal carotid artery (ICA) and vertebral artery
      (VA) blood flow using duplex Doppler ultrasound. Given that the VA supplies
      autonomic control centers in the brainstem, we hypothesized that graded
      sympathetic activation via lower body negative pressure (LBNP) would reduce ICA
      but not VA blood flow. ICA and VA blood flow were measured during two protocols:
      Protocol-1, low-to-moderate LBNP (-10, -20, -30, -40 Torr) and Protocol-2,
      moderate-to-high LBNP (-30, -50, -70 Torr). ICA and VA blood flow, diameter, and
      blood velocity were unaffected up to -40 LBNP. However, -50 and -70 LBNP evoked
      reductions in ICA and VA blood flow (e.g., -70 LBNP: %?VA-baseline= -27.6+/-3.0)
      that were mediated by decreases in both diameter and velocity (e.g., -70 LBNP:
      %?VA-baseline diameter= -7.5+/-1.9 and %?VA-baseline velocity= -13.6+/-1.7),
      which were comparable between vessels. Since hyperventilation during -70 LBNP
      reduced PETCO2, this decrease in PETCO2 was matched via voluntary
      hyperventilation. Reductions in ICA and VA blood flow during hyperventilation
      alone were significantly smaller than during -70 LBNP and were primarily mediated
      by decreases in velocity (%?VA-baseline velocity= -8.6+/-2.4; %?VA-baseline
      diameter= -0.05+/-0.56). These data demonstrate that both ICA and VA were
      unaffected by low-to-moderate sympathetic activation, whereas robust reflex
      mediated sympatho-excitation caused similar magnitudes of vasoconstriction in
      both arteries. Thus, contrary to our hypothesis, the ICA was not preferentially
      vasoconstricted by sympathetic activation.

PMID- 30188802
TI  - Contextualizing the lived experience of quality of life for persons with spinal
      cord injury: A mixed-methods application of the response shift model.
AB  - OBJECTIVE: The objective of this study was to gain greater insight into
      individuals' quality of life (QOL) definitions, appraisals, and adaptations
      following spinal cord injury (SCI). DESIGN: A mixed-methods design, applying the
      Schwartz and Sprangers response shift (RS) model. RS is a cognitive process
      wherein, in response to a change in health status, individuals change internal
      standards, values, or conceptualization of QOL Setting: Community-dwelling
      participants who receive medical treatment at a major Midwestern medical system
      and nearby Veterans' Affairs hospital. PARTICIPANTS: A purposive sample of
      participants with SCI (N = 40) completed semi-structured interviews and
      accompanying quantitative measures. INTERVENTIONS: Not applicable. OUTCOME
      MEASURES: Qualitative data were analyzed using content analysis to identify
      themes. Analysis of variance were performed to detect differences based on themes
      and QOL, well-being, and demographic and injury characteristics. RESULTS: Four RS
      themes were identified, capturing the range of participant perceptions of QOL.
      The themes ranged from complete RS, indicating active engagement in maintaining
      QOL, to awareness and comparisons redefining QOL, to a relative lack of RS.
      Average QOL ratings differed as a function of response shift themes. PROMIS
      Global Health, Anxiety, and Depression also differed as a function of RS themes.
      CONCLUSION: The RS model contextualizes differences in QOL definitions,
      appraisals, and adaptations in a way standardized QOL measures alone do not.

PMID- 30188803
TI  - Determining priorities in functional rehabilitation related to quality of life
      one-year following a traumatic spinal cord injury.
AB  - CONTEXT/OBJECTIVE: To determine the relationship between the different functional
      aspects (as determined by the Spinal Cord Independence Measure) and quality of
      life (QOL) following a traumatic spinal cord injury (TSCI), considering clinical
      confounding factors. DESIGN: Retrospective review of a prospective cohort
      Setting: A single Level-1 trauma center specialized in SCI care Participants: One
      hundred and forty-two individuals sustaining an acute traumatic SCI
      Interventions: Not applicable Outcome measures: The four QOL domains as assessed
      by the WHOQoL-bref questionnaire 6-12 months following a TSCI. RESULTS: Mobility
      subscore was the only functional aspect significantly associated with all QOL
      domains (physical, psychological, social and environmental). Females present
      better chronic social and environmental QOL when compared to males. The level of
      injury may also influence environmental QOL. CONCLUSION: Mobility training
      (mobility in bed, mobility with or without technical aids, transfers and stair
      management) should be an important part of the rehabilitation process in order to
      optimize chronic QOL following a TSCI.

PMID- 30188804
TI  - Implicit Theories of Interest: Finding Your Passion or Developing It?
AB  - People are often told to find their passion, as though passions and interests are
      preformed and must simply be discovered. This idea, however, has hidden
      motivational implications. Five studies examined implicit theories of interest
      the idea that personal interests are relatively fixed (fixed theory) or developed
      (growth theory). Whether assessed or experimentally induced, a fixed theory was
      more likely to dampen interest in areas outside people's existing interests
      (Studies 1-3). Individuals endorsing a fixed theory were also more likely to
      anticipate boundless motivation when passions were found, not anticipating
      possible difficulties (Study 4). Moreover, when it became difficult to engage in
      a new interest, interest flagged significantly more for people induced to hold a
      fixed rather than a growth theory of interest (Study 5). Urging people to find
      their passion may lead them to put all their eggs in one basket but then to drop
      that basket when it becomes difficult to carry.

PMID- 30188805
TI  - Enantioselectivity and residue analysis of fipronil in tea (Camellia sinensis) by
      ultra-performance liquid chromatography Orbitrap mass spectrometry.
AB  - This study aimed to determine the residues of fipronil, metabolites, and
      enantiomers in tea (Camellia sinensis) during tea planting and green tea
      manufacture. An AD-RH chiral column was used to separate the fipronil
      enantiomers. During tea planting, the half-lives of the sum of fipronil and
      metabolites were similar to those of fipronil, which were 2.37 and 3.88 days for
      tea shoots and mature leaves, respectively. The residues of fipronil and its
      metabolites increased 2.3-3.6-fold during green tea manufacture. The values for
      the processing factors of fipronil and metabolites ranged from 1.0 to 2.1. A
      slightly significant enantioselectivity of (R)- and (S)-fipronil was observed
      during tea planting and green tea manufacturing. The residue pattern indicated
      that fipronil should not be applied in tea gardens due to its long persistence.
      The maximum residual limits of fipronil and metabolites at 2 MUg kg-1 were
      considered optimal.

PMID- 30188806
TI  - "It's Not a Tumor": A Framework for Capitalizing on Individual Diversity to Boost
      Target Detection.
AB  - Even experts routinely miss infrequent targets, such as weapons in baggage scans
      or tumors in mammograms, because the visual system is not equipped to notice the
      unusual. To date, limited progress has been made toward improving human factors
      that mediate such critical diagnostic tasks. Here, we present a novel framework
      for pairing individuals' estimates to increase target detection. Using a wisdom
      of-crowds approach that capitalizes on the visual system's ability to efficiently
      combine information, we demonstrated how averaging two noninteracting
      individuals' continuous estimates of whether a briefly presented image contained
      a prespecified target can significantly boost detection across a range of tasks.
      Furthermore, we showed how pairing individuals' estimates to maximize
      decorrelated patterns of performance in one task can optimize performance on a
      separate task. These results make significant advances toward combating severe
      deficits in target detection using straightforward applications for maximizing
      performance within limited pools of observers.

PMID- 30188807
TI  - Quadrivalent Meningococcal Vaccine Uptake Among Men Who Have Sex With Men During
      a Meningococcal Outbreak in Los Angeles County, California, 2016-2017.
AB  - OBJECTIVE: The objective of our study was to assess meningococcal ACWY (MenACWY)
      vaccine uptake among men who have sex with men (MSM) during an ongoing, invasive
      meningococcal disease outbreak in Southern California. This research was
      important to inform future vaccination uptake interventions for this high
      priority population. METHODS: We conducted venue-based sampling to recruit and
      enroll MSM living in Los Angeles County, California, from December 2016 through
      February 2017. We conducted bivariate and multivariable analyses to evaluate
      associations between MenACWY vaccine uptake and other predetermined factors.
      RESULTS: Of 368 participants, 138 (37.5%) reported receiving the MenACWY vaccine.
      In multivariable analyses, older age (adjusted odds ratio [aOR] = 2.57; 95%
      confidence interval [CI], 1.31-5.03), previous diagnosis of a sexually
      transmitted infection (aOR = 2.22; 95% CI, 1.14-4.30), belief that MenACWY
      vaccine is important (aOR = 3.49; 95% CI, 1.79-6.82), confidence in the MenACWY
      vaccine (aOR = 5.53; 95% CI, 3.11-9.83), and knowing someone who had been
      vaccinated (aOR = 5.82; 95% CI, 3.05-11.12) were significantly associated with
      MenACWY vaccine uptake. CONCLUSIONS: Our findings reflect low uptake of the
      recommended MenACWY vaccine among MSM after a local outbreak, despite public
      health efforts. In addition to ongoing, widespread campaigns to inform MSM about
      local outbreaks and vaccination recommendations, MSM may be responsive to direct
      outreach from peers who have been vaccinated.

PMID- 30188809
TI  - A Wearable Multi-modal Bio-sensing System Towards Real-world Applications.
AB  - Multi-modal bio-sensing has recently been used as effective research tools in
      affective computing, autism, clinical disorders, and virtual reality among other
      areas. However, none of the existing bio-sensing systems support multi-modality
      in a wearable manner outside well-controlled laboratory environments with
      research-grade measurements. This work attempts to bridge this gap by developing
      a wearable multi-modal bio-sensing system capable of collecting, synchronizing,
      recording and transmitting data from multiple bio-sensors: PPG, EEG, eye-gaze
      headset, body motion capture, GSR, etc. while also providing task modulation
      features including visual-stimulus tagging. This study describes the development
      and integration of the various components of our system. We evaluate the
      developed sensors by comparing their measurements to those obtained by a standard
      research-grade bio-sensors. We first evaluate different sensor modalities of our
      headset, namely earlobe-based PPG module with motion-noise canceling for ECG
      during heart-beat calculation. We also compare the steady-state visually evoked
      potentials (SSVEP) measured by our shielded dry EEG sensors with the potentials
      obtained by commercially available dry EEG sensors. We also investigate the
      effect of head movements on the accuracy and precision of our wearable eye-gaze
      system. Furthermore, we carry out two practical tasks to demonstrate the
      applications of using multiple sensor modalities for exploring previously
      unanswerable questions in bio-sensing. Specifically, utilizing bio-sensing we
      show which strategy works best for playing Where is Waldo? visual-search game,
      changes in EEG corresponding to true versus false target fixations in this game,
      and predicting the loss/draw/win states through bio-sensing modalities while
      learning their limitations in a Rock-Paper-Scissors game.

PMID- 30188808
TI  - Pneumonia-Associated Hospitalizations, New York City, 2001-2014.
AB  - OBJECTIVES: Death certificate data indicate that the age-adjusted death rate for
      pneumonia and influenza is higher in New York City than in the United States.
      Most pneumonia and influenza deaths are attributed to pneumonia rather than
      influenza. Because most pneumonia deaths occur in hospitals, we analyzed hospital
      discharge data to provide insight into the burden of pneumonia in New York City.
      METHODS: We analyzed data for New York City residents discharged from New York
      State hospitals with a principal diagnosis of pneumonia, or a secondary diagnosis
      of pneumonia if the principal diagnosis was respiratory failure or sepsis, during
      2001-2014. We calculated mean annual age-adjusted pneumonia-associated
      hospitalization rates per 100 000 population and 95% confidence intervals (CIs).
      We examined data on pneumonia-associated hospitalizations by sociodemographic
      characteristics and colisted conditions. RESULTS: During 2001-2014, a total of
      495 225 patients residing in New York City were hospitalized for pneumonia,
      corresponding to a mean annual age-adjusted pneumonia-associated hospitalization
      rate of 433.8 per 100 000 population (95% CI, 429.3-438.3). The proportion of
      pneumonia-associated hospitalizations with in-hospital death was 12.0%. The mean
      annual age-adjusted pneumonia-associated hospitalization rate per 100 000
      population increased as area-based poverty level increased, whereas the
      percentage of pneumonia-associated hospitalizations with in-hospital deaths
      decreased with increasing area-based poverty level. The proportion of pneumonia
      associated hospitalizations that colisted an immunocompromising condition
      increased from 18.7% in 2001 to 33.1% in 2014. CONCLUSION: Sociodemographic
      factors and immune status appear to play a role in the epidemiology of pneumonia
      associated hospitalizations in New York City. Further study of pneumonia
      associated hospitalizations in at-risk populations may lead to targeted
      interventions.

PMID- 30188810
TI  - Acousto-optic Catheter Tracking Sensor for Interventional MRI Procedures.
AB  - OBJECTIVE: The objective of this paper is to introduce an acousto-optic optical
      fiber sensor for tracking catheter position during interventional magnetic
      resonance imaging (MRI) to overcome RF induced heating of active markers.
      METHODS: The sensor uses a miniature coil coupled to a piezoelectric transducer,
      which is in turn mechanically connected to an optical fiber. The piezoelectric
      transducer converts the RF signal to acoustic waves in the optical fiber over a
      region including a fiber Bragg grating (FBG). The elastic waves in the fiber
      modulates the FBG geometry and hence the reflected light in the optical fiber.
      Since the coil is much smaller than the RF wavelength and the signal is
      transmitted on the dielectric optical fiber, the sensor effectively reduces RF
      induced heating risk. Proof of concept prototypes of the sensor are implemented
      using commercially available piezoelectric transducers and optical fibers with
      FBGs. The prototypes are characterized in a 1.5T MRI system in comparison with an
      active tracking marker. RESULTS: Acousto-optical sensor shows linear response
      with flip angle and it can be used to detect signals from multiple coils for
      potential orientation detection. It has been successfully used to detect the
      position of a tacking coil in phantom in an imaging experiment. CONCLUSION:
      Acousto-optical sensing is demonstrated for tracking catheters during
      interventional MRI. Real-time operation of the sensor requires sensitivity
      improvements like using a narrow band FBG. SIGNIFICANCE: Acousto-optics provides
      a compact solution to sense RF signals in MRI with dielectric transmission lines.

PMID- 30188811
TI  - Computational Modeling of Ultrasonic Subthalamic Nucleus Stimulation.
AB  - OBJECTIVE: To explore the potential of ultrasonic modulation of plateau-potential
      generating subthalamic nucleus neurons (STN), by modeling their interaction with
      continuous and pulsed ultrasonic waves. METHODS: A computational model for
      ultrasonic stimulation of the STN is created by combining the Otsuka-model with
      the bilayer sonophore model. The neuronal response to continuous and pulsed
      ultrasonic waves is computed in parallel for a range of frequencies, duty cycles,
      pulse repetition frequencies, and intensities. RESULTS: Ultrasonic intensity in
      continuous-wave stimulation determines the firing pattern of the STN. Three
      observed spiking modes in order of increasing intensity are low frequency
      spiking, high frequency spiking with significant spike-frequency and spike
      amplitude adaptation, and a silenced mode. Continuous-wave stimulation has little
      capability to manipulate the saturated spiking rate in the high frequency spiking
      mode. In contrast, STN firing rates induced by pulsed ultrasound insonication
      will saturate to the pulse repetition frequency with short latencies, for
      sufficiently large intensity and repetition frequency. CONCLUSION: Computational
      results show that the activity of plateau-potential generating subthalamic
      nucleus neurons can be modulated by selection of the stimulus parameters. Low
      intensities result in repetitive firing, while higher intensities silence the
      STN. Pulsed ultrasonic stimulation results in a shorter saturation latency and is
      able to modulate spiking rates. SIGNIFICANCE: Stimulation or suppresion of the
      STN is important in the treatment of Parkinson's disease, e.g., in deep brain
      stimulation. This explorative study on ultrasonic modulation of the STN, could be
      a step in the direction of minimally invasive alternatives to conventional deep
      brain stimulation.

PMID- 30188812
TI  - Height-from-Polarisation with Unknown Lighting or Albedo.
AB  - We present a method for estimating surface height directly from a single
      polarisation image simply by solving a large, sparse system of linear equations.
      To do so, we show how to express polarisation constraints as equations that are
      linear in the unknown height. The local ambiguity in the surface normal azimuth
      angle is resolved globally when the optimal surface height is reconstructed. Our
      method is applicable to dielectric objects exhibiting diffuse and specular
      reflectance, though lighting and albedo must be known. We relax this requirement
      by showing that either spatially varying albedo or illumination can be estimated
      from the polarisation image alone using nonlinear methods. In the case of
      illumination, the estimate can only be made up to a binary ambiguity which we
      show is a generalised Bas-relief transformation corresponding to the
      convex/concave ambiguity. We believe that our method is the first passive,
      monocular shape-from-x technique that enables well-posed height estimation with
      only a single, uncalibrated illumination condition. We present results on real
      world data, including in uncontrolled, outdoor illumination.

PMID- 30188813
TI  - Transferable Representation Learning with Deep Adaptation Networks.
AB  - Domain adaptation generalizes a learning machine across source domain and target
      domain under different distributions. Recent studies reveal that deep neural
      networks can learn transferable features generalizing well to similar novel tasks
      for domain adaptation. However, as deep features eventually transition from
      general to specific along the network, feature transferability drops
      significantly in higher task-specific layers with increasing domain discrepancy.
      To formally reduce the dataset shift and enhance the feature transferability in
      task-specific layers, this paper presents a novel framework for deep adaptation
      networks, which generalizes deep convolutional neural networks to domain
      adaptation. The framework embeds the deep features of all task-specific layers to
      reproducing kernel Hilbert spaces (RKHSs) and optimally match different domain
      distributions. The deep features are made more transferable by exploring low
      density separation of target-unlabeled data and very deep architectures, while
      the domain discrepancy is further reduced using multiple kernel learning for
      maximal testing power of kernel embedding matching. This leads to a minimax game
      framework that learns transferable features with statistical guarantees, and
      scales linearly with unbiased estimate of kernel embedding. Extensive empirical
      evidence shows that the proposed networks yield state-of-the-art results on
      standard visual domain adaptation benchmarks.

PMID- 30188814
TI  - Discriminant Functional Learning of Color Features for the Recognition of Facial
      Action Units and their Intensities.
AB  - Color is a fundamental image feature of facial expressions. For example, when we
      furrow our eyebrows in anger, blood rushes in and a reddish color becomes
      apparent around that area of the face. Surprisingly, these image properties have
      not been exploited to recognize the facial action units (AUs) associated with
      these expressions. Herein, we present the first system to do recognition of AUs
      and their intensities using these functional color changes. These color features
      are shown to be robust to changes in identity, gender, race, ethnicity and skin
      color. Specifically, we identify the chromaticity changes defining the transition
      of an AU from inactive to active and use an innovative Gabor transform-based
      algorithm to gain invariance to the timing of these changes. Because these image
      changes are given by functions rather than vectors, we use a functional
      classifiers to identify the most discriminant color features of an AU and its
      intensities. We demonstrate that, using these discriminant color features, one
      can achieve results superior to those of the state-of-the-art. Finally, we define
      an algorithm that allows us to use the learned functional color representation in
      still images. This is done by learning the mapping between images and the
      identified functional color features in videos. Our algorithm works in realtime,
      i.e., >30 frames/second/CPU thread.

PMID- 30188815
TI  - Robust recovery of temporal overlap between network activity using transient
      informed spatio-temporal regression.
AB  - Functional magnetic resonance imaging (fMRI) is a non-invasive tomographic
      imaging modality that has provided insights into systems-level brain function.
      New analysis methods are emerging to study the dynamic behavior of brain
      activity. The innovation-driven co-activation pattern (iCAP) approach is one such
      approach that relies on the detection of timepoints with significant transient
      activity to subsequently retrieve spatially and temporally overlapping large
      scale brain networks. To recover temporal profiles of the iCAPs for further time
      resolved analysis, spatial patterns are fitted back to the activity-inducing
      signals. In this crucial step, spatial dependencies can hinder the recovery of
      temporal overlapping activity. To overcome this effect, we propose a novel back
      projection method that optimally fits activity-inducing signals given a set of
      transient timepoints and spatial maps of iCAPs, thus taking into account both
      spatial and temporal constraints. Validation on simulated data shows that
      transient-based constraints improve the quality of fitted time courses. Further
      evaluation on experimental data demonstrates that over- and underfitting are
      prevented by the use of optimized spatio-temporal constraints. Spatial and
      temporal properties of resulting iCAPs support that brain activity is
      characterized by the recurrent co-activation and co-deactivation of spatially
      overlapping large-scale brain networks. This new approach opens new avenues to
      explore the brain's dynamic core.

PMID- 30188816
TI  - A Novel Data-Driven Cardiac Gating Signal Extraction Method for PET.
AB  - Compared to external device based approaches, a data-driven gating technique in
      PET imaging is advantageous as it does not require additional hardware or
      procedure. Currently, data-driven cardiac gating is less studied than respiratory
      gating. The aim of this study is to develop a robust data-driven cardiac gating
      approach for clinical application. First, the central location of the heart is
      obtained from the corresponding CT image. A cylinder-shaped volume of interest
      (VOI) centered at the central location of the heart is used to confine cardiac
      signal calculation. The cardiac signal modeling the expansion/contraction of the
      heart is calculated using the second order moment of the tracer distribution in
      the VOI in the projection domain. The signal to noise ratio (SNR) of the cardiac
      motion signal is defined as the energy of the cardiac frequency components over
      the energy of other non-cardiac frequencies. The optimal cardiac signal with
      maximal SNR is obtained through an iterative optimization of signal extraction
      parameters. To validate our method, simulations of different scan parameters
      including tracer uptake and noise level were generated from the 4D XCAT phantom.
      Quantitative evaluation was achieved by comparing the extracted signal with the
      truth in the simulation study. Our method was also applied to 19 patients with
      high myocardium uptake and compared with the conventional center-of-mass based
      data-driven method. The simulation study suggests that two major limiting factors
      in the performance of our method are the myocardium/body uptake ratio and the
      count rate of the whole field of view. High accuracy of the detected signal was
      observed with myocardium/body uptake ratio>7 and count rate>100 counts/ms.
      Cardiac peak frequencies were successfully detected in all 19 patients using our
      method, while the conventional method obtained peaks in only 12 data sets. Our
      method was also visually validated by gated reconstructions. In summary, we have
      developed a novel dedicated data-driven cardiac gating method for PET by tracking
      the contraction/expansion of the heart during the scan. Quantitative evaluation
      using simulations and qualitative validation with clinical datasets both
      demonstrate that our method is a robust alternative to the device-based method
      with a high success rate.

PMID- 30188817
TI  - Learning Cross-Modality Representations from Multi-Modal Images.
AB  - Machine learning algorithms can have difficulties adapting to data from different
      sources, for example from different imaging modalities. We present and analyze
      three techniques for unsupervised cross-modality feature learning, using a shared
      autoencoder-like convolutional network that learns a common representation from
      multi-modal data. We investigate a form of feature normalization, a learning
      objective that minimizes crossmodality differences, and modality dropout, in
      which the network is trained with varying subsets of modalities. We measure the
      same-modality and cross-modality classification accuracies and explore whether
      the models learn modality-specific or shared features. This paper presents
      experiments on two public datasets, with knee images from two MRI modalities,
      provided by the Osteoarthritis Initiative, and brain tumor segmentation on four
      MRI modalities from the BRATS challenge. All three approaches improved the cross
      modality classification accuracy, with modality dropout and per-feature
      normalization giving the largest improvement. We observed that the networks tend
      to learn a combination of cross-modality and modality-specific features. Overall,
      a combination of all three methods produced the most cross-modality features and
      the highest cross-modality classification accuracy, while maintaining most of the
      samemodality accuracy.

PMID- 30188818
TI  - Dynamic in vivo chest x-ray dark-field imaging in mice.
AB  - X-ray grating interferometry is a powerful emerging tool in biomedical imaging,
      providing access to three complementary image modalities. In addition to the
      conventional attenuation modality, interferometry provides a phase modality that
      visualises soft tissue structures, and a dark-field modality that relates to the
      number and size of sub-resolution scattering objects. A particularly strong dark
      field signal originates from the alveoli or air sacs in the lung. Dark-field lung
      radiographs in animal models have already shown increased sensitivity in
      diagnosing lung diseases such as lung cancer or emphysema, compared to
      conventional x-ray chest radiography. However, to date, x-ray dark-field lung
      imaging has either averaged information over several breaths or has been captured
      during a breath hold. In this report we demonstrate the first time-resolved dark
      field imaging of a breath cycle in a mechanically ventilated mouse, in vivo,
      which was obtained using a grating interferometer. We achieved a time resolution
      of 0.1 s, visualizing the changes in the dark-field, phase and attenuation images
      during inhalation and exhalation. These measurements show that the dark-field
      signal depends on the air volume and hence alveolar dimensions of the lung.
      Conducting this type of scan with animal disease models would help to locate the
      optimum breath point for single-image diagnostic dark-field imaging, and could
      indicate if the changes in the dark-field signal during breath provide a
      diagnostically useful complementary measure.

PMID- 30188819
TI  - Multitransducer SAW Device Architecture for Passive Wireless Sensor Tags.
AB  - A new architecture of surface acoustic wave (SAW) sensor tags with lower
      insertion loss and enhanced sensitivity is investigated. It efficiently employs
      two transducer arrays at the input and output of the acoustic channel,
      respectively. The improved sensitivity is attained due to a higher number of
      stronger constituent signals contributing constructively to the device response.
      An efficient matrix modeling approach is generalized to permit fast design and
      synthesis of the multitransducer sensor tags with arbitrary topologies. The
      modeling approach consistency is validated by energy balance. Several simulation
      examples of new 6-GHz SAW sensor tags, implemented on 128 degrees YX-LiNbO3
      substrate, are presented and compared against a conventional reflective delay
      line device. The effects of finite electrode resistivity and SAW beam diffraction
      are evaluated numerically, and the SAW sensor-tag design tradeoffs and principles
      are established.

PMID- 30188820
TI  - Parallel Attentive Correlation Tracking.
AB  - Psychological and cognitive findings indicate that human visual perception is
      attentive and selective, which may process spatial and appearance selective
      attentions in parallel. By reflecting some aspects of these attentions, this
      paper presents a novel correlation filter (CF) based tracking approach,
      corresponding to processing a local and a semi-local background domains,
      respectively. In the local domain, inspired by the Gestalt principle of figure
      ground segregation, we leverage an efficient Boolean map representation, which
      characterizes an image by a set of Boolean maps via randomly thresholding its
      color channels, yielding a location response map as a weighted sum of all Boolean
      maps. The Boolean maps capture the topological structures of target and its scene
      with different granularities, thereby enabling to effectively improve tracking of
      non-rectangular objects. Alternatively, in the semi-local domains, we introduce a
      novel distractor-resilient metric regularization into CF, which acts as a force
      to push distractors into negative space. Consequently, the unwanted boundary
      effects of CF can be effectively alleviated. Finally, both models associated with
      the local and the semi-local domains are seamlessly integrated into a Bayesian
      framework, and the tracked location is determined by maximizing its likelihood
      function. Extensive evaluations on the OTB50, OTB100, VOT2016 and VOT2017
      tracking benchmarks demonstrate that the proposed method achieves favorable
      performance against a variety of state-of-the-art trackers with a speed of 45 fps
      on a single CPU.

PMID- 30188821
TI  - AIPNet: Image-to-Image Single Image Dehazing with Atmospheric Illumination Prior.
AB  - The atmospheric scattering and absorption gives rise to the natural phenomenon of
      haze, which severely affects the visibility of scenery. Thus, the image taken by
      the camera can easily lead to over brightness and ambiguity. To resolve an
      illposed and intractable problem of single image dehazing, we propose a
      straightforward but remarkable prior-atmospheric illumination prior in this
      paper. The extensive statistical experiments for different colorspaces and
      theoretical analyses indicate that the atmospheric illumination in hazy weather
      mainly has a great influence on the luminance channel in YCrCb colorspace, and
      has less impact on the chrominance channels. According to this prior, we try to
      maintain the intrinsic color of hazy scene and enhance its visual contrast. To
      this end, we apply the multiscale convolutional networks that can automatically
      identify hazy regions and restore deficient texture information. Compared with
      previous methods, the deep CNNs not only achieve an end-to-end trainable model,
      but also accomplish an easy imageto-image system architecture. The extensive
      comparisons and analyses with existing approaches demonstrate that the proposed
      approach achieves the state-of-the-art performance on several dehazing effects.

PMID- 30188822
TI  - iForest: Interpreting Random Forests via Visual Analytics.
AB  - As an ensemble model that consists of many independent decision trees, random
      forests generate predictions by feeding the input to internal trees and
      summarizing their outputs. The ensemble nature of the model helps random forests
      outperform any individual decision tree. However, it also leads to a poor model
      interpretability, which significantly hinders the model from being used in fields
      that require transparent and explainable predictions, such as medical diagnosis
      and financial fraud detection. The interpretation challenges stem from the
      variety and complexity of the contained decision trees. Each decision tree has
      its unique structure and properties, such as the features used in the tree and
      the feature threshold in each tree node. Thus, a data input may lead to a variety
      of decision paths. To understand how a final prediction is achieved, it is
      desired to understand and compare all decision paths in the context of all tree
      structures, which is a huge challenge for any users. In this paper, we propose a
      visual analytic system aiming at interpreting random forest models and
      predictions. In addition to providing users with all the tree information, we
      summarize the decision paths in random forests, which eventually reflects the
      working mechanism of the model and reduces users' mental burden of
      interpretation. To demonstrate the effectiveness of our system, two usage
      scenarios and a qualitative user study are conducted.

PMID- 30188823
TI  - DQNViz: A Visual Analytics Approach to Understand Deep Q-Networks.
AB  - Deep Q-Network (DQN), as one type of deep reinforcement learning model, targets
      to train an intelligent agent that acquires optimal actions while interacting
      with an environment. The model is well known for its ability to surpass
      professional human players across many Atari 2600 games. Despite the superhuman
      performance, in-depth understanding of the model and interpreting the
      sophisticated behaviors of the DQN agent remain to be challenging tasks, due to
      the long-time model training process and the large number of experiences
      dynamically generated by the agent. In this work, we propose DQNViz, a visual
      analytics system to expose details of the blind training process in four levels,
      and enable users to dive into the large experience space of the agent for
      comprehensive analysis. As an initial attempt in visualizing DQN models, our work
      focuses more on Atari games with a simple action space, most notably the Breakout
      game. From our visual analytics of the agent's experiences, we extract useful
      action/reward patterns that help to interpret the model and control the training.
      Through multiple case studies conducted together with deep learning experts, we
      demonstrate that DQNViz can effectively help domain experts to understand,
      diagnose, and potentially improve DQN models.

PMID- 30188824
TI  - Patterns and Pace: Quantifying Diverse Exploration Behavior with Visualizations
      on the Web.
AB  - The diverse and vibrant ecosystem of interactive visualizations on the web
      presents an opportunity for researchers and practitioners to observe and analyze
      how everyday people interact with data visualizations. However, existing metrics
      of visualization interaction behavior used in research do not fully reveal the
      breadth of peoples' open-ended explorations with visualizations. One possible way
      to address this challenge is to determine high-level goals for visualization
      interaction metrics, and infer corresponding features from user interaction data
      that characterize different aspects of peoples' explorations of visualizations.
      In this paper, we identify needs for visualization behavior measurement, and
      develop corresponding candidate features that can be inferred from users'
      interaction data. We then propose metrics that capture novel aspects of peoples'
      open-ended explorations, including exploration uniqueness and exploration pacing.
      We evaluate these metrics along with four other metrics recently proposed in
      visualization literature by applying them to interaction data from prior
      visualization studies. The results of these evaluations suggest that these new
      metrics 1) reveal new characteristics of peoples' use of visualizations, 2) can
      be used to evaluate statistical differences between visualization designs, and 3)
      are statistically independent of prior metrics used in visualization research. We
      discuss implications of these results for future studies, including the potential
      for applying these metrics in visualization interaction analysis, as well as
      emerging challenges in developing and selecting metrics depicting visualization
      explorations.

PMID- 30188825
TI  - SRVis: Towards Better Spatial Integration in Ranking Visualization.
AB  - Interactive ranking techniques have substantially promoted analysts' ability in
      making judicious and informed decisions effectively based on multiple criteria.
      However, the existing techniques cannot satisfactorily support the analysis tasks
      involved in ranking large-scale spatial alternatives, such as selecting optimal
      locations for chain stores, where the complex spatial contexts involved are
      essential to the decision-making process. Limitations observed in the prior
      attempts of integrating rankings with spatial contexts motivate us to develop a
      context-integrated visual ranking technique. Based on a set of generic design
      requirements we summarized by collaborating with domain experts, we propose
      SRVis, a novel spatial ranking visualization technique that supports efficient
      spatial multi-criteria decision-making processes by addressing three major
      challenges in the aforementioned context integration, namely, a) the presentation
      of spatial rankings and contexts, b) the scalability of rankings' visual
      representations, and c) the analysis of context-integrated spatial rankings.
      Specifically, we encode massive rankings and their cause with scalable matrix
      based visualizations and stacked bar charts based on a novel two-phase
      optimization framework that minimizes the information loss, and the flexible
      spatial filtering and intuitive comparative analysis are adopted to enable the in
      depth evaluation of the rankings and assist users in selecting the best spatial
      alternative. The effectiveness of the proposed technique has been evaluated and
      demonstrated with an empirical study of optimization methods, two case studies,
      and expert interviews.

PMID- 30188826
TI  - A Heuristic Approach to Value-Driven Evaluation of Visualizations.
AB  - To interpret data visualizations, people must determine how visual features map
      onto concepts. For example, to interpret colormaps, people must determine how
      dimensions of color (e.g., lightness, hue) map onto quantities of a given measure
      (e.g., brain activity, correlation magnitude). This process is easier when the
      encoded mappings in the visualization match people's predictions of how visual
      features will map onto concepts, their inferred mappings. To harness this
      principle in visualization design, it is necessary to understand what factors
      determine people's inferred mappings. In this study, we investigated how inferred
      color-quantity mappings for colormap data visualizations were influenced by the
      background color. Prior literature presents seemingly conflicting accounts of how
      the background color affects inferred color-quantity mappings. The present
      results help resolve those conflicts, demonstrating that sometimes the background
      has an effect and sometimes it does not, depending on whether the colormap
      appears to vary in opacity. When there is no apparent variation in opacity,
      participants infer that darker colors map to larger quantities (dark-is-more
      bias). As apparent variation in opacity increases, participants become biased
      toward inferring that more opaque colors map to larger quantities (opaque-is-more
      bias). These biases work together on light backgrounds and conflict on dark
      backgrounds. Under such conflicts, the opaque-is-more bias can negate, or even
      supersede the dark-is-more bias. The results suggest that if a design goal is to
      produce colormaps that match people's inferred mappings and are robust to changes
      in background color, it is beneficial to use colormaps that will not appear to
      vary in opacity on any background color, and to encode larger quantities in
      darker colors.

PMID- 30188827
TI  - Mapping Color to Meaning in Colormap Data Visualizations.
AB  - To interpret data visualizations, people must determine how visual features map
      onto concepts. For example, to interpret colormaps, people must determine how
      dimensions of color (e.g., lightness, hue) map onto quantities of a given measure
      (e.g., brain activity, correlation magnitude). This process is easier when the
      encoded mappings in the visualization match people's predictions of how visual
      features will map onto concepts, their inferred mappings. To harness this
      principle in visualization design, it is necessary to understand what factors
      determine people's inferred mappings. In this study, we investigated how inferred
      color-quantity mappings for colormap data visualizations were influenced by the
      background color. Prior literature presents seemingly conflicting accounts of how
      the background color affects inferred color-quantity mappings. The present
      results help resolve those conflicts, demonstrating that sometimes the background
      has an effect and sometimes it does not, depending on whether the colormap
      appears to vary in opacity. When there is no apparent variation in opacity,
      participants infer that darker colors map to larger quantities (dark-is-more
      bias). As apparent variation in opacity increases, participants become biased
      toward inferring that more opaque colors map to larger quantities (opaque-is-more
      bias). These biases work together on light backgrounds and conflict on dark
      backgrounds. Under such conflicts, the opaque-is-more bias can negate, or even
      supersede the dark-is-more bias. The results suggest that if a design goal is to
      produce colormaps that match people's inferred mappings and are robust to changes
      in background color, it is beneficial to use colormaps that will not appear to
      vary in opacity on any background color, and to encode larger quantities in
      darker colors.

PMID- 30188828
TI  - Juniper: A Tree+ Table Approach to Multivariate Graph Visualization.
AB  - Analyzing large, multivariate graphs is an important problem in many domains, yet
      such graphs are challenging to visualize. In this paper, we introduce a novel,
      scalable, tree+table multivariate graph visualization technique, which makes many
      tasks related to multivariate graph analysis easier to achieve. The core
      principle we follow is to selectively query for nodes or subgraphs of interest
      and visualize these subgraphs as a spanning tree of the graph. The tree is laid
      out linearly, which enables us to juxtapose the nodes with a table visualization
      where diverse attributes can be shown. We also use this table as an adjacency
      matrix, so that the resulting technique is a hybrid node-link/adjacency matrix
      technique. We implement this concept in Juniper and complement it with a set of
      interaction techniques that enable analysts to dynamically grow, restructure, and
      aggregate the tree, as well as change the layout or show paths between nodes. We
      demonstrate the utility of our tool in usage scenarios for different multivariate
      networks: a bipartite network of scholars, papers, and citation metrics and a
      multitype network of story characters, places, books, etc.

PMID- 30188829
TI  - NLIZE: A Perturbation-Driven Visual Interrogation Tool for Analyzing and
      Interpreting Natural Language Inference Models.
AB  - With the recent advances in deep learning, neural network models have obtained
      state-of-the-art performances for many linguistic tasks in natural language
      processing. However, this rapid progress also brings enormous challenges. The
      opaque nature of a neural network model leads to hard-to-debug-systems and
      difficult-to-interpret mechanisms. Here, we introduce a visualization system
      that, through a tight yet flexible integration between visualization elements and
      the underlying model, allows a user to interrogate the model by perturbing the
      input, internal state, and prediction while observing changes in other parts of
      the pipeline. We use the natural language inference problem as an example to
      illustrate how a perturbation-driven paradigm can help domain experts assess the
      potential limitation of a model, probe its inner states, and interpret and form
      hypotheses about fundamental model mechanisms such as attention.

PMID- 30188830
TI  - Restoring the Awareness in the Occluded Visual Field for Optical See-Through Head
      Mounted Displays.
AB  - Recent technical advancements support the application of Optical See-Through Head
      Mounted Displays (OST-HMDs) in critical situations like navigation and
      manufacturing. However, while the form-factor of an OST-HMD occupies less of the
      user's visual field than in the past, it can still result in critical oversights,
      e.g., missing a pedestrian while driving a car. In this paper, we design and
      compare two methods to compensate for the loss of awareness due to the occlusion
      caused by OST-HMDs. Instead of presenting the occluded content to the user, we
      detect motion that is not visible to the user and highlight its direction either
      on the edge of the HMD screen, or by activating LEDs placed in the user's
      peripheral vision. The methods involve an offline stage, where the occluded
      visual field and location of each indicator and its associated occluded region of
      interest (OROI) are determined, and an online stage, where an enhanced optical
      flow algorithm tracks the motion in the occluded visual field. We have
      implemented both methods on a Microsoft HoloLens and an ODG R-9. Our prototype
      systems achieved success rates of 100% in an objective evaluation, and 98.90% in
      a pilot user study. Our methods are able to compensate for the loss of safety
      critical information in the occluded visual field for state-of-the-art OST-HMDs
      and can be extended for their future generations.

PMID- 30188831
TI  - PizzaText: Text Entry for Virtual Reality Systems Using Dual Thumbsticks.
AB  - We present PizzaText, a circular keyboard layout technique for text entry in
      virtual reality (VR) environments that uses the dual thumbsticks of a hand-held
      game controller. Text entry is a common activity in VR environments but remains
      challenging with existing techniques and keyboard layouts that is largely based
      on QWERTY. Our technique makes text entry simple, easy, and efficient, even for
      novice users. The technique uses a hand-held controller because it is still an
      important input device for users to interact with VR environments. To allow rapid
      search of characters, PizzaText divides a circle into slices and each slice
      contains 4 characters. To enable fast selection, the user uses the right
      thumbstick for traversing the slices, and the left thumbstick for choosing the
      letters. The design of PizzaText is based on three criteria: efficiency,
      learnability, and ease-of-use. In our first study, six potential layouts are
      considered and evaluated. The results lead to a design with 7 slices and 4
      letters per slice. The final design is evaluated in a five-day study with 10
      participants. The results show that novice users can achieve an average of 8.59
      Words per Minute (WPM), while expert users are able to reach 15.85 WPM, with just
      two hours of training.

PMID- 30188832
TI  - Towards Efficient Visual Guidance in Limited Field-of-View Head-Mounted Displays.
AB  - Understanding, navigating, and performing goal-oriented actions in Mixed Reality
      (MR) environments is a challenging task and requires adequate information
      conveyance about the location of all virtual objects in a scene. Current Head
      Mounted Displays (HMDs) have a limited field-of-view where augmented objects may
      be displayed. Furthermore, complex MR environments may be comprised of a large
      number of objects which can be distributed in the extended surrounding space of
      the user. This paper presents two novel techniques for visually guiding the
      attention of users towards out-of-view objects in HMD-based MR: the 3D Radar and
      the Mirror Ball. We evaluate our approaches against existing techniques during
      three different object collection scenarios, which simulate real-world
      exploratory and goal-oriented visual search tasks. To better understand how the
      different visualizations guide the attention of users, we analyzed the head
      rotation data for all techniques and introduce a novel method to evaluate and
      classify head rotation trajectories. Our findings provide supporting evidence
      that the type of visual guidance technique impacts the way users search for
      virtual objects in MR.

PMID- 30188833
TI  - Revisiting Trends in Augmented Reality Research: A Review of the 2nd Decade of
      ISMAR (2008-2017).
AB  - In 2008, Zhou et al. presented a survey paper summarizing the previous ten years
      of ISMAR publications, which provided invaluable insights into the research
      challenges and trends associated with that time period. Ten years later, we
      review the research that has been presented at ISMAR conferences since the survey
      of Zhou et al., at a time when both academia and the AR industry are enjoying
      dramatic technological changes. Here we consider the research results and trends
      of the last decade of ISMAR by carefully reviewing the ISMAR publications from
      the period of 2008-2017, in the context of the first ten years. The numbers of
      papers for different research topics and their impacts by citations were analyzed
      while reviewing them-which reveals that there is a sharp increase in AR
      evaluation and rendering research. Based on this review we offer some
      observations related to potential future research areas or trends, which could be
      helpful to AR researchers and industry members looking ahead.

PMID- 30188834
TI  - Hyper-Objective Vortices.
AB  - Almost all properties of vector fields, including magnitude, direction, lambda2
      and vorticity change under arbitrary movements of the observer. This is
      undesirable since measurements of physical properties should ideally not depend
      on the way the (virtual) measurement device moves. There are some properties that
      are invariant under certain types of reference frame transformations: Galilean
      invariance (invariance under equal-speed translation) and objectivity (invariance
      under any smooth rotation and translation of the reference frame). In this paper,
      we introduce even harder conditions than objectivity: we demand invariance under
      any smooth similarity transformation (rotation, translation and uniform scale) as
      well as invariance under any smooth affine transformation of the reference frame.
      We show that these new hyper-objective measures allow the extraction of vortices
      that change their volume or deform. Further, we present a generic approach that
      transforms almost any vortex measure into a hyper-objective one. We apply our
      methods to vortex extraction in 2D and 3D vector fields, and analyze the
      numerical robustness, extraction time and the minimization residuals for the
      Galilean invariant, objective, and the two new hyper-objective approaches.

PMID- 30188835
TI  - A Novel Method of Emergency Situation Detection for a Brain-Controlled Vehicle by
      Combining EEG Signals With Surrounding Information.
AB  - In this paper, to address the safety of brain-controlled vehicles under emergency
      situations, we propose a novel method of emergency situation detection by fusing
      driver electroencephalography (EEG) signals with surrounding information. We
      first build a novel EEG-based detection model of driver emergency braking
      intention. We then recognize emergency situations by fusing the result of the
      proposed EEG-based intention detection model with that of the obstacle detection
      model based on surrounding information. The real-time detection system of driver
      emergency braking intention is implemented on an embedded system, and the driver
      and-hardware-in-the-loop-experiment of the proposed detection method of emergency
      situations is performed. Experimental results show that the proposed method can
      detect emergency situations with the system accuracy of 94.89%, false alarm rate
      of 0.05%, and response time of 540 ms. This paper has important values in the
      future development of brain-controlled vehicles, human-centric advanced driver
      assistant systems, and self-driving vehicles and opens a new avenue on how
      cognitive neuroscience may be applied to human-machine integration.

PMID- 30188836
TI  - User-Adaptive Assistance of Assistive Knee Braces for Gait Rehabilitation.
AB  - Patients suffering from neurological and orthopedic diseases or injuries usually
      have mobility impairment problems, and they require customized rehabilitation
      training to recover. In recent years, robotic assistive devices have been widely
      studied for gait rehabilitation. In this paper, methods to determine user
      adaptive assistance of assistive knee braces (AKBs) in gait rehabilitation are
      investigated. A fuzzy expert system, which takes a patient's physical condition
      and gait analysis results as inputs, is proposed to configure suitable levels of
      different assistive functions of the AKB. During gait rehabilitation, the AKB
      generates a reference knee trajectory according to the patient's individual gait
      pattern, and the interaction force is controlled through a hybrid impedance
      controller considering the individual assistive function configuration. The
      proposed methods are verified through clinical pilot studies of a patient with
      lower limb weakness. Experimental results show that AKB with the proposed control
      strategies can provide effective assistance to improve the patient's gait
      performance during gait rehabilitation.

PMID- 30188837
TI  - End-to-End Noise Model for Intra-Body Terahertz Nanoscale Communication.
AB  - In vivo wireless nanosensor networks (iWNSNs) are paving the way toward
      transformative healthcare solutions. These networks are expected to enable a
      plethora of applications, including drug-delivery, bio-sensing, and health
      monitoring. With the development of miniature plasmonic signal sources, antennas,
      and detectors, wireless communications among intrabody nanodevices will
      expectedly be enabled in the terahertz (THz) frequency band (0.1-10 THz). Several
      propagation models were recently developed to analyze and assess the feasibility
      of intra-body electromagnetic (EM) nanoscale communication. The emphasis of these
      works has mainly been on understanding the propagation of EM signals through
      biological media, with limited focus on the intra-body noise sources and their
      impact on the system performance. In this paper, a stochastic noise model for
      iWNSNs is presented in which the individual noise sources that impact intra-body
      systems operating in the THz frequency band are analyzed. The overall noise
      contributions are composed of three distinctive constituents, namely, Johnson
      Nyquist noise, black-body noise, and Doppler-shift-induced noise. The probability
      distribution of each noise component is derived, and a comprehensive analytical
      approach is developed to obtain the total noise power-spectral density. The model
      is further validated via 2-D particle simulations as the active transport motion
      of particles is conveyed in the presented framework. The developed models serve
      as the starting point for a rigorous end-to-end channel model that enables the
      proper estimation of data rate, channel capacity, and other key parameters, which
      are all factors of the noise environment.

PMID- 30188838
TI  - Registration and Fusion of Thermographic and Visual-Light Images in Neurosurgery.
AB  - An intraoperative imaging system facilitating the localisation and
      characterisation of functional areas, pathological tissue, or perfusion
      disorders, could enormously support medical decisions during neurosurgical
      interventions and, thus, reduce the risk for the patients. To provide both
      structural and functional information of the brain tissue to the surgeon, a novel
      multimodal approach based on the measurement of long-wave infrared radiation and
      visual-light imaging is very promising. In this contribution, we discuss various
      methods for the registration and fusion of thermographic and visual-light images.
      The methods are evaluated quantitatively and qualitatively regarding their
      practicability during surgery. Furthermore, we introduce appropriate
      architectures for a digital hardware implementation of the registration and
      fusion algorithms. The designs are implemented on our reconfigurable
      intraoperative imaging system, revealing real-time processing performance.

PMID- 30188839
TI  - Multiplierless Implementation of Noisy Izhikevich Neuron with Low Cost Digital
      Design.
AB  - Fast speed and high accuracy implementation of biological plausible neural
      networks are vital key objectives to achieve new solutions to model, simulate and
      cure the brain diseases. Efficient hardware implementation of Spiking Neural
      Networks (SNN) is a significant approach in biological neural networks. This
      paper presents a Multiplierless Noisy Izhikevich Neuron (MNIN) model, which is
      used for digital implementation of biological neural networks in large scale.
      Simulation results show that the MNIN model reproduces the same operations of the
      original noisy Izhikevich neuron. The proposed model has a low-cost hardware
      implementation property compared with the original neuron model. The FPGA
      realization results demonstrated that the MNIN model follows the different
      spiking patterns, appropriately.

PMID- 30188840
TI  - The Promise of Mobile Technologies for the Health Care System in the Developing
      World: A Systematic Review.
AB  - Evolution of mobile technologies and their rapid penetration to people's daily
      lives, especially in the developing countries, have highlighted mobile health, or
      m-health, as a promising solution to improve health outcomes. Several studies
      have been conducted that characterize the impact of m-health solutions in
      resource-limited settings and assess their potential to improve health care. The
      aim of the present paper is twofold: i) present an overview of the background and
      significance of m-health, and ii) summarize and discuss the existing evidence for
      the effectiveness of m-health in the developing world. A systematic search in the
      literature was performed in Pubmed, Scopus, as well as reference lists, and a
      broad sample of 98 relevant articles was identified which were then categorized
      into five wider m-health categories. Although statistically significant
      conclusions cannot be drawn since the majority of studies relied on small scale
      trials and limited assessment of long term effects, this paper provides a
      systematic and extensive analysis of the advantages, disadvantages, and
      challenges of m-health in developing countries in an attempt to determine future
      research directions of m-health interventions.

PMID- 30188841
TI  - Robust Methods for Real-time Diabetic Foot Ulcer Detection and Localization on
      Mobile Devices.
AB  - Current practice for Diabetic Foot Ulcers (DFU) screening involves detection and
      localization by podiatrists. Existing automated solutions either focus on
      segmentation or classification. In this work, we design deep learning methods for
      real-time DFU localization. To produce a robust deep learning model, we collected
      an extensive database of 1775 images of DFU. Two medical experts produced the
      ground truths of this dataset by outlining the region of interest of DFU with an
      annotator software. Using 5-fold cross-validation, overall, Faster R-CNN with
      InceptionV2 model using two-tier transfer learning achieved a mean average
      precision of 91.8%, the speed of 48 ms for inferencing a single image and with a
      model size of 57.2 MB. To demonstrate the robustness and practicality of our
      solution to real-time prediction, we evaluated the performance of the models on a
      NVIDIA Jetson TX2 and a smartphone app. This work demonstrates the capability of
      deep learning in real-time localization of DFU, which can be further improved
      with a more extensive dataset.

PMID- 30188842
TI  - Functional connectivity analysis of cerebellum using spatially constrained
      spectral clustering.
AB  - The human cerebellum contains almost fifty percent of the neurons in the brain,
      although its volume does not exceed ten percent of the total brain volume. The
      goal of this study is to derive the functional network of the cerebellum during
      resting-state and then compare the ensuing group networks between males and
      females. Towards this direction, a spatially constrained version of the classic
      spectral clustering algorithm is proposed and then compared against conventional
      spectral graph theory approaches, such as, spectral clustering, and N-cut, on
      synthetic data as well as on resting-state fMRI data obtained from the Human
      Connectome Project (HCP). The extracted atlas was combined with the anatomical
      atlas of cerebellum resulting to a functional atlas with 46 Regions of Interest
      (ROIs). As a final step, a gender-based network analysis of cerebellum was
      performed using the data-driven atlas along with the concept of the Minimum
      Spanning Trees. The simulation analysis results confirm the dominance of the
      spatially constrained spectral clustering approach in discriminating activation
      patterns under noisy conditions. The network analysis results reveal
      statistically significant differences in the optimal tree organization between
      males and females. In addition, the dominance of the Left VI lobule in both
      genders supports the results reported in a previous study of ours. To our
      knowledge, the extracted atlas comprises the first resting-state atlas of
      cerebellum based on HCP data.

PMID- 30188843
TI  - Evaluation of Gaze Tracking Calibration for Longitudinal Biomedical Imaging
      Studies.
AB  - Gaze tracking is a promising technology for studying the visual perception of
      clinicians during image-based medical exams. It could be used in longitudinal
      studies to analyze their perceptive process, explore human-machine interactions,
      and develop innovative computer-aided imaging systems. However, using a remote
      eye tracker in an unconstrained environment and over time periods of weeks
      requires a certain guarantee of performance to ensure that collected gaze data
      are fit for purpose. We report the results of evaluating eye tracking calibration
      for longitudinal studies. First, we tested the performance of an eye tracker on a
      cohort of 13 users over a period of one month. For each participant, the eye
      tracker was calibrated during the first session. The participants were asked to
      sit in front of a monitor equipped with the eye tracker, but their position was
      not constrained. Second, we tested the performance of the eye tracker on
      sonographers positioned in front of a cart-based ultrasound scanner. Experimental
      results show a decrease of accuracy between calibration and later testing of 0.30
      degrees  and a further degradation over time at a rate of 0.13 degrees . month-1.
      The overall median accuracy was 1.00 degrees  50.9 pixels and the overall median
      precision was 0.16 degrees  8.3 pixels. The results from the ultrasonography
      setting show a decrease of accuracy of 0.16 degrees  between calibration and
      later testing. This slow degradation of gaze tracking accuracy could impact the
      data quality in long-term studies. Therefore, the results we present here can
      help in planning such long-term gaze tracking studies.

PMID- 30188844
TI  - Incremental Class Learning for Hierarchical Classification.
AB  - Objects can be described in hierarchical semantics, and people also perceive them
      this way. It leads to the need for hierarchical classification in machine
      learning. On the other hand, when a new data that belongs to a new class is
      given, the existing classification methods should be retrained for all data
      including the new data. To deal with these issues, we propose an adaptive
      resonance theory-supervised predictive mapping for hierarchical classification
      (ARTMAP-HC) network that allows incremental class learning for raw data without
      normalization in advance. Our proposed ARTMAP-HC is composed of hierarchically
      stacked modules, and each module incorporates two fuzzy ARTMAP networks.
      Regardless of the level of the class hierarchy and the number of classes for each
      level, ARTMAP-HC is able to incrementally learn sequentially added input data
      belonging to new classes. By using a novel online normalization process, ARTMAP
      HC can classify the new data without prior knowledge of the maximum value of the
      dataset. By adopting the prior labels appending process, the class dependency
      between class hierarchy levels is reflected in ARTMAP-HC. The effectiveness of
      the proposed ARTMAP-HC is validated through experiments on hierarchical
      classification datasets. To demonstrate the applicability, ARTMAP-HC is applied
      to a multimedia recommendation system for digital storytelling.

PMID- 30188845
TI  - Mistakes.

PMID- 30188847
TI  - Retraction notice: Diagnosis and management of cemental tear: a case report. Gen
      Dent. 2014;62(3):e12-e13.

PMID- 30188846
TI  - Diagnosis: a simple bone cyst.

PMID- 30188848
TI  - The backbone of implant prosthetics: single posterior implant crowns.

PMID- 30188849
TI  - Does liposomal bupivacaine fulfill an unmet need in dentistry?

PMID- 30188850
TI  - Something from nothing: creating success with minimal remaining tooth structure.

PMID- 30188852
TI  - The impact of taste perception on the health of the aging population.

PMID- 30188853
TI  - Oral adverse events associated with targeted cancer therapies.
AB  - Over the past decade, targeted therapies have emerged as promising forms of
      cancer treatment and are increasingly included in chemotherapeutic regimens for
      an ever-growing list of human cancers. Targeted therapies are so-named due to
      their specific targeting of dysregulated signaling pathways in cancer cells. This
      enhanced discrimination between tumor and normal cells is a more promising and
      efficacious approach to cancer treatment than conventional cytotoxic
      chemotherapy. However, targeted therapies still have side effects, and some
      manifest in the oral cavity. Oral adverse events tend to be mild and thus may be
      overlooked in the context of a patient's overarching diagnosis and management.
      These oral lesions are often noted during an intraoral examination and identified
      in the context of the patient's medical history and medication list. It is
      imperative that the dentist be informed of the oral sequelae of targeted
      therapies. Many of these side effects can be successfully managed in a palliative
      manner with conservative therapy. This article discusses the clinical
      presentations and treatment of intraoral adverse events attributable to the
      following classes of targeted therapies: epidermal growth factor receptor
      inhibitors, mammalian target of rapamycin inhibitors, angiogenesis inhibitors,
      and selected tyrosine kinase inhibitors.

PMID- 30188851
TI  - The challenges of treating patients with trigeminal neuralgia.

PMID- 30188854
TI  - Bond strength of resin cement to ceramic with simplified primers and pretreatment
      solutions.
AB  - Manufacturers have recently introduced surface primers and pretreatment solutions
      that reportedly simplify the bonding process of resin cements to ceramics through
      various combinations of etchant and coupling agents. This study evaluated the
      shear bond strength (SBS) of a resin cement to a lithium disilicate glass-ceramic
      material pretreated with various new surface treatment solutions and compared the
      results to those of a control group prepared with the traditional application of
      hydrofluoric acid (HF) and silane. Resin cement was bonded to pretreated glass
      ceramic surfaces, and specimens were tested for SBS after 24 hours of storage in
      water. Traditional surface treatment of lithium disilicate glass ceramic with HF
      and silane resulted in a significantly greater mean SBS than did simplified
      primer solutions. There were no statistically significant differences among the
      simplified pretreatment groups. In the control group, the majority of failures
      were due to mixed adhesive-cohesive fracture, while in the simplified treatment
      groups the failure mode was usually adhesive, suggesting a weaker interface.

PMID- 30188855
TI  - Formation of biofilm on various implant abutment materials.
AB  - The characteristics of prosthetic implant components, such as the type, material,
      and surface roughness of abutments, can affect biofilm formation. Since an ideal
      abutment surface for the reduction of bacterial adhesion has yet to be found,
      this in vitro study aimed to quantify biofilm formation on laser-treated
      titanium, zirconia, and titanium surfaces. Sterile titanium, zirconia, and laser
      treated titanium discs were placed in sterile 48-well plates. Biofilm formation
      was induced by adding sterilized, unstimulated human saliva and suspensions of
      Porphyromonas gingivalis (Pg), Aggregatibacter actinomycetemcomitans (Aa), and
      Prevotella intermedia (Pi) to the wells. Viable bacteria in the biofilm were
      quantified with real-time polymerase chain reaction in conjunction with propidium
      monoazide. The disc material, the type of bacteria, and their interactions had
      significant effects on the bacterial counts. On all surfaces, the Pg count was
      significantly higher than both the Pi and Aa counts (P = 0.0001). The highest
      count of periodontal pathogens was found on laser-treated surfaces. The second
      highest and the lowest counts were found on zirconia and titanium surfaces,
      respectively.

PMID- 30188856
TI  - The erosive potential of additive artificial flavoring in bottled water.
AB  - Acidic beverage consumption is a well-recognized contributor to extrinsic dental
      erosion. Although the pH values of some commercially available bottled waters are
      below neutral pH, water is still considered to be a safe and healthy choice.
      Artificial flavoring liquids or powders, known as water enhancers (WEs), have
      been introduced to the market to modify the taste of water. The purposes of the
      present study were to measure the pH and titratable acidity of WEs and to perform
      gravimetric analysis of teeth immersed in solutions of WEs mixed with different
      brands of bottled water in order to determine the erosive potential in vitro. The
      pH and titratable acidity using 0.1M sodium hydroxide were calculated for 7
      brands of WEs added to 3 brands of bottled water, which had different initial pH
      values. Extracted human molar teeth were submerged in each combination of
      solutions for gravimetric analysis. Distilled water was used as the positive
      control and citric acid as the negative control. Data were analyzed with 2-way
      analysis of variance and post hoc Tukey-Kramer testing (P = 0.05). The pH value
      (2.9-3.0) and titratable acidity (32.2-35.3 mmol/L hydroxide) of all of the
      experimental solutions were considered acidic, regardless of the WE brand.
      Average tooth structure loss after 1 month of immersion in the solutions was 4%,
      and surface changes were consistent with erosive dissolution. The results showed
      that adding a WE to water significantly increases the potential for dental
      erosion. The high content of citric acid in WEs is believed to be the cause.
      Patients should be advised to use WEs with caution.

PMID- 30188857
TI  - Glycemic control among patients with physician-managed type 2 diabetes.
AB  - Outcomes for treatment, overall oral health status, and periodontal disease
      progression in patients with type 2 diabetes mellitus (T2DM) have been associated
      with glycemic control as measured by hemoglobin A1c (HbA1c) levels. Due to the
      high prevalence of T2DM among patient populations in the United States, this
      study sought to assess baseline levels of glycemic control for patients with a
      known diagnosis of T2DM who were under the care of a physician and to identify
      management solutions for these patients. All patients included in this study were
      prescreened to ensure that they were dentate, had been diagnosed with T2DM at
      least 3 months previously, were under the care of a physician for diabetes
      management, and had no changes to their diabetes-related medications for 3 months
      or more (N = 822). The patients meeting those criteria were then screened in
      person, and those who had moderate to severe chronic periodontitis, had at least
      20 teeth, and met other inclusion/exclusion criteria were qualified to
      participate in the study (N = 214). After the patients fasted, a whole blood
      sample was drawn and subjected to HbA1c testing. The mean (SD) HbA1c for the
      qualified patients was 7.76% (1.79%), and the values ranged from 5.1% to 18.8%.
      Among the 214 qualified individuals, 150 (70.1%) had HbA1c values greater than
      6.5%. Of these 150 patients, 80 (53.3%, or 37.4% of the total screened sample)
      presented with HbA1c values greater than 8.0%. The majority of patients with
      periodontitis and physician-managed T2DM did not meet ideal standards for
      glycemic control. Dental healthcare providers should consider consultation and/or
      advanced screening for diabetic patients seeking dental care.

PMID- 30188858
TI  - Treatment planning and dental technology for patients with implanted cardiac
      devices.
AB  - Implantable cardiac devices are increasingly common in the dental patient
      population. These devices include cardiac pacemakers, implantable cardioverters
      defibrillators, and combination designs. To safely follow through with treatment,
      the clinician first must identify the patient's underlying medical condition
      warranting the device and consider the condition as well as the device in
      determining diagnosis, drug selection, appointment length, follow-up, and outcome
      expectations. Modern implantable devices are engineered to be resistant to
      electromagnetic field changes in the day-to-day activities of the wearer, and
      little of the technology used in dentistry today has been shown to create an
      electromagnetic field strong enough to have the potential to affect performance
      of an implantable cardiac device. The dentist should use the greatest caution
      with electrocautery devices and choose a bipolar system whenever possible.
      Consulting with a patient's cardiologist or general physician is a prudent step
      for the practitioner prior to undertaking a treatment plan that requires multiple
      or long appointments to accomplish and utilizes technology that produces an
      electromagnetic field.

PMID- 30188859
TI  - Combating antibiotic resistance: a survey on the antibiotic-prescribing habits of
      dentists.
AB  - Adherence to clinical guidelines is recommended to promote appropriate antibiotic
      use in dentistry and address concerns about increasing antibiotic resistance.
      Guidelines for antibiotic prophylaxis before invasive dental procedures were
      updated in 2007 and 2015. In an effort to inform antibiotic stewardship efforts,
      a study was undertaken to assess the knowledge of antibiotic usage guidelines and
      antibiotic-prescribing practices among Minnesota dentists. During September 2015,
      a 22-question online survey was sent to the state dental association membership.
      Among 437 respondents, dentists reported a median of 4 antibiotic prophylaxis and
      5 treatment prescriptions per month. Dentists reported prescribing antibiotics
      for prophylaxis before invasive dental procedures for patients with "high-risk
      conditions" (84%) and localized swelling (70%) as well as for a number of reasons
      that are not recommended by current guidelines, such as an upcoming vacation for
      the patient (38%), gingival pain (38%), legal concerns (24%), patient demand
      (22%), and failed local anesthesia (21%). Dentists defined high-risk conditions
      as a history of infective endocarditis (75%), prosthetic cardiac valve (70%),
      selected congenital heart disease (68%), cardiac transplantation with cardiac
      valvulopathy (4%), and primary care physician recommendation (59%). In addition,
      some dentists assigned a high-risk category to conditions that do not fall within
      current guideline recommendations, including prosthetic joints (39%), poorly
      controlled type 2 diabetes (27%), human immunodeficiency virus (18%), chronic
      kidney disease (13%), mitral valve prolapse (11%), all congenital heart disease
      (4%), and well-controlled type 2 diabetes (1%). Respondents indicated that common
      challenges to stewardship of antibiotic use included perceived conflicting
      provider guidelines (44%), conflicting scientific evidence (44%), or lack of
      information on antibiotic selection (19%) or risks (23%). Dentists reported
      greater antibiotic use than currently recommended by existing guidelines.
      Antibiotic stewardship efforts in dentistry should address challenges to
      guideline adherence.

PMID- 30188860
TI  - Laser therapy as an adjunct in the treatment of sodium hypochlorite extrusion
      through a root perforation: a case report.
AB  - Accidental sodium hypochlorite extrusion can occur during endodontic irrigation
      procedures. The symptoms appear immediately and include severe pain, swelling,
      and probable tissue necrosis adjacent to the root of the treated tooth. Treatment
      of sodium hypochlorite extrusion involves immediate and copious saline irrigation
      to neutralize the area and prescription of analgesic, anti-inflammatory, and
      antibiotic medications. Low-level laser therapy (LLLT) might be useful as an
      adjuvant treatment for damaged soft tissues to improve healing. This case report
      describes the treatment of accidental extrusion of 1% sodium hypochlorite through
      a root canal perforation in a mandibular incisor during endodontic treatment. The
      extrusion caused minor swelling within the mentolabial sulcus and a large area of
      necrosis in the gingivolabial mucosa and right edentulous premolar area.
      Conventional treatment was performed in association with LLLT. Clinical and
      radiographic examinations after 6 months showed complete healing of the necrotic
      area without paresthesia and the repair of apical tissues.

PMID- 30188861
TI  - Use of a mandibular torus for autogenous grafting: a case report.
AB  - Conventional treatment for the management of 2- to 3-walled intrabony defects is
      the use of allograft or alloplasts. Autogenous grafts are the gold standard
      because of their osteogenic potential. Mandibular tori are an ideal site for
      harvesting bone because their excision causes no structural, esthetic, or
      functional compromise to the patient. This case report describes the use of an
      autogenous graft obtained from a mandibular torus. The graft was utilized, in
      particulate form, to fill an intrabony defect at the mandibular right central
      incisor. The mandibular torus provided sufficient graft material and eliminated
      the need for a second surgical site. A follow-up at 1 year revealed reduction in
      clinical attachment loss and complete resolution of tooth mobility.

PMID- 30188862
TI  - Multiple bilateral mixed-density lesions of the mandible and Restricted jaw
      opening.

PMID- 30188863
TI  - Clinical implications, diagnosis, and treatment of a giant frontoethmoid osteoma.
AB  - Osteomas are benign, asymptomatic fibro-osseous tumors that are most commonly
      observed in the paranasal sinuses and sometimes are found in imaging examinations
      that were taken for other reasons. Giant osteomas are rarely found in the frontal
      and ethmoid sinuses but, when they are, they may cause intracranial and orbital
      complications. The aims of this case report are to describe a frontoethmoid
      osteoma in a 40-year-old woman, discuss the characteristics of this lesion
      through cone beam computed tomography (CBCT) imaging, and review the options for
      treatment. A CBCT examination performed for the purpose of orthodontic diagnosis
      revealed the presence of a large, well-defined, lobular, hyperdense mass that
      occupied a sizeable area of the frontal sinus and extended to the ethmoid sinus.
      The patient did not report any pain. Based on the physical and imaging
      characteristics of the mass, the location and size of the lesion, and the
      patient's age, the diagnosis was a giant frontoethmoid osteoma. Due to its
      enhanced field of view, CBCT may enable earlier diagnosis of lesions that affect
      the maxillofacial region.

PMID- 30188864
TI  - Anterior lingual mandibular bone depression: differential diagnosis of periapical
      inflammatory disorders.
AB  - Lingual mandibular bone depressions mainly affect the posterior region of the
      mandible. Depressions in the anterior region are rare, frequently posing
      difficulties in diagnosis. The aim of this article is to present a case of an
      anterior lingual mandibular bone depression (ALMBD) that was radiographically
      superimposed on the roots of anterior teeth. A 43-year-old man was referred for
      evaluation of a slight depression on the lingual surface of the anterior
      mandible. The depression was associated with a well-defined radiolucent area
      superimposed on the roots of the right canine and incisors. All teeth in the area
      proved to be vital, and cone beam computed tomography (CBCT) revealed a lingual
      depression in the area. The final diagnosis was an ALMBD, and the patient
      underwent clinical and radiographic follow-up examinations for 22 months that
      revealed no alterations in the area. When anterior mandibular radiolucencies are
      superimposed on the roots of the adjacent teeth, ALMBDs should be considered in
      the differential diagnosis along with periapical cysts and granulomas.
      Radiographic and CBCT analyses are useful to avoid unnecessary endodontic and
      surgical approaches.

PMID- 30188865
TI  - Palatal obturator designed by 3-dimensional prototyping for a patient with a
      large ameloblastoma: a case report.
AB  - The aim of the present report was to detail the advantages of using 3-dimensional
      (3D) prototyping in the planning, modeling, and manufacturing of an immediate
      palatal obturator for a 62-year-old man who underwent a left total maxillectomy
      to remove a solid, multicystic ameloblastoma. The prosthesis provided favorable
      restoration of stomatognathic functions, including speech, swallowing, and
      mastication. The use of an immediate obturator prosthesis made with 3D technology
      is an important aid in the treatment of patients diagnosed with tumors in the
      head and neck region.

PMID- 30188866
TI  - Patient positioning verification for proton therapy using proton range probes:
      experimental validation in phantom geometries.
AB  - We present a proof of principle, experimental validation of the potential of
      proton 'Range Probes' (RP) for patient positioning verification in proton
      therapy. In this work, we have evaluated experimentally the accuracy of RP by
      using tissue-like samples and an in-house developed multilayer ionization chamber
      (MLIC). In addition we build on our previous, simulation based work to present
      first experimental measurements of RP through anthropomorphic phantoms to detect
      either rotational or translational positioning errors. For this, a technique has
      been proposed to characterize the Residual Integral Depth Dose Curve (RIDDC)
      after range mixing. This parametrization has been used to evaluate the similarity
      between Monte Carlo calculated error scenarios of the database and the measured
      RIDDC, while considering the intrinsic uncertainties of both modalities in order
      to deduce the positioning error. Finally, the additional dose applied to the
      patient when using clinical RP with known fluence has been estimated by measuring
      the local dose of a single RP. In tissue phantoms, the prediction accuracy of the
      water equivalent path length was 0.70%, with the highest deviations being found
      in low density samples (up to 5.67%). In addition, the results of the patient
      positioning verification measurements demonstrated that using carefully selected
      RPs, one dimensional translational or rotational errors could be detected with an
      accuracy of 1 mm and 2 degrees  respectively, and that these would be associated
      with a low additional dose burden to the patient. In summary, these promising
      results suggest that the RP method could be a simple, fast and low-dose tool for
      verifying patient set-up during proton therapy treatment.

PMID- 30188867
TI  - Lysyl-tRNA synthetase-expressing colon spheroids induce M2 macrophage
      polarization to promote metastasis.
AB  - Lysyl-tRNA synthetase (KRS) functions canonically in cytosolic translational
      processes. However, KRS is highly expressed in colon cancer, and localizes to
      distinct cellular compartments upon phosphorylations (i.e., the plasma membranes
      after T52 phosphorylation and the nucleus after S207 phosphorylation), leading to
      probably alternative noncanonical functions. It is unknown how other subcellular
      KRSs crosstalk with environmental cues during cancer progression. Here, we
      demonstrate that the KRS-dependent metastatic behavior of colon cancer spheroids
      within 3D gels requires communication between cellular molecules and
      extracellular soluble factors and neighboring cells. Membranous KRS and nuclear
      KRS were found to participate in invasive cell dissemination of colon cancer
      spheroids in 3D gels. Cancer spheroids secreted GAS6 via a KRS-dependent
      mechanism and caused the M2 polarization of macrophages, which activated the
      neighboring cells via secretion of FGF2/GROalpha/M-CSF to promote cancer
      dissemination under environmental remodeling via fibroblast-mediated laminin
      production. Analyses of tissues from clinical colon cancer patients and Krs-/+
      animal models for cancer metastasis supported the roles of KRS, GAS6, and M2
      macrophages in KRS-dependent positive feedback between tumors and environmental
      factors. Altogether, KRS in colon cancer cells remodels the microenvironment to
      promote metastasis, which can thus be therapeutically targeted at these
      bidirectional KRS-dependent communications of cancer spheroids with environmental
      cues.

PMID- 30188868
TI  - Antigenic sites in influenza H1 hemagglutinin display species-specific
      immunodominance.
AB  - Hemagglutination inhibition (HI) titers are a major correlate of protection for
      influenza-related illness. The influenza virus hemagglutinin possesses antigenic
      sites that are the targets of HI active antibodies. Here, a panel of mutant
      viruses each lacking a classically defined antigenic site was created to compare
      the species-specific immunodominance of the antigenic sites in a clinically
      relevant hemagglutinin. HI active antibodies of antisera from influenza virus
      infected mice targeted sites Sb and Ca2. HI active antibodies of guinea pigs were
      not directed against any specific antigenic site, although trends were observed
      toward Sb, Ca2, and Sa. HI titers of antisera from infected ferrets were
      significantly affected by site Sa. HI active antibodies of adult humans followed
      yet another immunodominance pattern, in which sites Sb and Sa were
      immunodominant. When comparing the HI profiles among different species by
      antigenic cartography, animals and humans grouped separately. This study provides
      characterizations of the antibody-mediated immune responses against the head
      domain of a recent H1 hemagglutinin in animals and humans.

PMID- 30188871
TI  - Metformin Regulates the Expression of SK2 and SK3 in the Atria of Rats With Type
      2 Diabetes Mellitus Through the NOX4/p38MAPK Signaling Pathway.
AB  - We previously found that metformin regulates the ion current conducted by the
      small conductance calcium-activated potassium channels (SK channels) in the atria
      of rats with type 2 diabetes mellitus (T2DM) as well as the mRNA and protein
      expression of the SK2 and SK3 subtypes of SK channels. In this study, we
      hypothesized that the nicotinamide adenine dinucleotide phosphate oxidase 4
      (NOX4)/p38 mitogen-activated protein kinase (p38MAPK) signaling pathway was
      involved in the metformin-mediated regulation of SK2 and SK3 expression in the
      atria of rats with T2DM. We randomly divided Wistar rats into the control group,
      the untreated T2DM group, the metformin-treated group, the group receiving
      subcutaneous injections of the nicotinamide adenine dinucleotide phosphate
      oxidase (NOX) inhibitor diphenyleneiodonium (DPI), and the group receiving tail
      vein injections of the p38MAPK agonist anisomycin. Real-time polymerase chain
      reaction, Western blot, and immunohistochemistry were applied to examine the
      expression levels of SK2, SK3, NOX4, and phospho-p38MAPK (p-p38MAPK) mRNAs and
      proteins in the atrial tissue of relevant groups. We observed that the expression
      levels of NOX4 mRNA and protein and p-p38MAPK protein were significantly elevated
      in the atria of rats with T2DM compared with the control group. In addition, SK2
      protein expression was reduced, whereas SK3 protein expression was increased. The
      8-week treatment with metformin markedly reduced the expression levels of NOX4
      mRNA and protein and p-p38MAPK protein, upregulated the SK2 expression, and
      downregulated the SK3 expression. Tail vein injection with anisomycin
      significantly increased the p-p38MAPK expression while further inhibiting the
      expression of SK2 and enhancing the expression of SK3. Subcutaneous injection
      with DPI considerably inhibited the expression of NOX4, further enhanced the
      expression of SK2 and suppressed the expression of SK3. In addition, subcutaneous
      injection with DPI significantly suppressed the phosphorylation of p38MAPK. In
      conclusion, the NOX4/p38MAPK signaling pathway mediates the downregulation of SK2
      and the upregulation of SK3 in the atria of rats with T2DM. Long-term metformin
      treatment upregulates SK2 protein expression and downregulates SK3 protein
      expression by inhibiting the NOX4/p38MAPK signaling pathway.

PMID- 30188870
TI  - Metoprolol and Nebivolol Prevent the Decline of the Redox Status of Low-Molecular
      Weight Aminothiols in Blood Plasma of Rats During Acute Cerebral Ischemia.
AB  - Cerebral ischemia has previously been shown to cause a systemic decrease in
      levels of the reduced forms of low-molecular-weight aminothiols [cysteine (Cys),
      homocysteine (Hcy), and glutathione (GSH)] in blood plasma. In this study, we
      examined the effect of beta-adrenergic receptor (beta-AR) antagonists metoprolol
      (Met) and nebivolol (Neb) on the redox status of these aminothiols during acute
      cerebral ischemia in rats. We used a model of global cerebral ischemia (bilateral
      occlusion of common carotid arteries with hypotension lasting for 10 minutes).
      The antagonists were injected 1 hour before surgery. Total and reduced Cys, Hcy,
      and GSH levels were measured 40 minutes after the start of reperfusion. Neb (0.4
      and 4 mg/kg) and Met (8 and 40 mg/kg) treatment increased the levels of reduced
      aminothiols and the global methylation index in the hippocampus. The treatments
      also prevented any decrease in reduced aminothiol levels in blood plasma during
      ischemia. Although both of these drugs eliminated delayed postischemic
      hypoperfusion, only Neb reduced neuronal damage in the hippocampus. The results
      indicate an essential role of beta1-AR blockage in the maintenance of redox
      homeostasis of aminothiols in the plasma and brain during acute cerebral
      ischemia.

PMID- 30188872
TI  - Button battery and magnet ingestions in the pediatric patient.
AB  - PURPOSE OF REVIEW: Pediatric foreign body ingestion is a common occurrence that
      presents a challenge both to pediatric gastroenterologists and primary care
      providers. Increasing prevalence of smaller, more technologically advanced toys
      in the household has resulted in an increased exposure to higher voltage
      batteries and powerful magnets that carry a high incidence of morbidity and
      mortality. This review highlights the latest findings regarding the patients at
      risk for button battery and magnet ingestions, the symptoms of presentation, and
      complications of these objects in contributing to long-standing gastrointestinal
      injury. RECENT FINDINGS: Button batteries may lead to esophageal injury within a
      few hours. Batteries retained in the esophagus are larger in diameter on average
      and size is associated with esophageal impaction as well as higher grade
      esophageal injury. Magnet ingestions, when multiple or with another metallic
      object, are often initially asymptomatic but may have acute worsening, and
      therefore warrant close monitoring. SUMMARY: Button battery and magnet ingestions
      have increased in incidence over the past two decades. Recent literature
      demonstrates that higher voltage, larger lithium button batteries, and prevalence
      of high-powered magnets can lead to significant morbidity. High suspicion, early
      referral, and removal may lead to improved outcomes.

PMID- 30188869
TI  - Targeted hypoxia reduction restores T cell infiltration and sensitizes prostate
      cancer to immunotherapy.
AB  - Despite the success of immune checkpoint blockade against melanoma, many "cold"
      tumors like prostate cancer remain unresponsive. We found that hypoxic zones were
      prevalent across preclinical prostate cancer and resisted T cell infiltration
      even in the context of CTLA-4 and PD-1 blockade. We demonstrated that the hypoxia
      activated prodrug TH-302 reduces or eliminates hypoxia in these tumors.
      Combination therapy with this hypoxia-prodrug and checkpoint blockade cooperated
      to cure more than 80% of tumors in the transgenic adenocarcinoma of the mouse
      prostate-derived (TRAMP-derived) TRAMP-C2 model. Immunofluorescence imaging
      showed that TH-302 drives an influx of T cells into hypoxic zones, which were
      expanded by checkpoint blockade. Further, combination therapy reduced myeloid
      derived suppressor cell density by more than 50%, and durably reduced the
      capacity of the tumor to replenish the granulocytic subset. Spontaneous prostate
      tumors in TRAMP transgenic mice, which completely resist checkpoint blockade,
      showed minimal adenocarcinoma tumor burden at 36 weeks of age and no evidence of
      neuroendocrine tumors with combination therapy. Survival of Pb-Cre4, Ptenpc-/
      Smad4pc-/- mice with aggressive prostate adenocarcinoma was also significantly
      extended by this combination of hypoxia-prodrug and checkpoint blockade. Hypoxia
      disruption and T cell checkpoint blockade may sensitize some of the most
      therapeutically resistant cancers to immunotherapy.

PMID- 30188873
TI  - In pursuit of control and elimination: update on hepatitis A and B epidemiology
      and prevention strategies.
AB  - PURPOSE OF REVIEW: This review describes the impact of recommendations for
      routine immunization of infants and children against hepatitis A and hepatitis B,
      the changing epidemiology of these infections, and the remaining challenges to
      controlling or eliminating these diseases in the United States. RECENT FINDINGS:
      Rates of hepatitis A and B have significantly declined because of childhood
      vaccination programs and long-term protection provided by infant immunization.
      However, hepatitis A immunization rates remain lower than other vaccines, and
      outbreaks continue to occur in part due to a growing number of susceptible
      adults. The Advisory Committee on Immunization Practice has updated pre and
      postexposure prophylaxis and travel recommendations for hepatitis A prevention in
      young infants, as well as recommendations to reduce ongoing perinatal
      transmission of hepatitis B. SUMMARY: Pediatric healthcare providers should
      continue to immunize all infants against hepatitis A and B and ensure that no
      child outgrows the pediatric practice without being vaccinated. To address
      hepatitis A, providers should be aware of new recommendations for unimmunized
      travelers, use vaccines to prevent and control outbreaks, and ensure postexposure
      prophylaxis. Universal vaccination of infants against hepatitis B should begin
      before hospital discharge. The prevention of perinatal transmission is critical
      for control and possible eradication of hepatitis B.

PMID- 30188874
TI  - 18F-FDG PET/CT in a Patient With Pregnancy and Lactation-Associated Osteoporosis.
AB  - A 33-year-old woman in the 6th month postpartum and breast-feeding period
      suffered from acute thoracolumbar pain for 1 month. She presented with slightly
      decreased serum calcium level. Other laboratory assessments were unremarkable.
      Considering the worsening symptom and her strong demand to exclude potential
      malignancy, F-FDG PET/CT was performed. Multiple FDG-avid foci in the thoracic
      and lumbar vertebra were detected on FDG PET, corresponding to vertebral
      compression fractures on CT, and diffuse FDG uptake was seen within bilateral
      breast, and dual-X ray absorptiometry showed markedly decreased bone mineral
      density, all of which supported the diagnosis of pregnancy and lactation
      associated osteoporosis.

PMID- 30188875
TI  - Continuing Education for Nursing Contact Hours and CRNI(r) Recertification Units.

PMID- 30188876
TI  - Angioplasty Versus Stenting for Pulmonary Vein Stenosis After Radiofrequency
      Ablation for Atrial Fibrillation-A Systemic Review and Meta-analysis.

PMID- 30188877
TI  - Asystole Due to Spontaneous Hemopericardiac Tamponade in a Patient on Warfarin.

PMID- 30188878
TI  - Psychotropic Drugs and Liver Toxicity.

PMID- 30188879
TI  - Expression of Allograft Inflammatory Factor-1 (AIF-1) in Hepatocellular
      Carcinoma.
AB  - BACKGROUND Allograft inflammatory factor-1 (AIF-1) is a cytoplasmic protein
      cloned from activated macrophages in human and rat allografts. AIF-1 has been
      identified as a modulator of inflammatory response, and recently published
      studies have shown its increased expression in carcinogenesis. However, there are
      still limited data on the potential functional role of AIF-1 in hepatocellular
      carcinoma (HCC). MATERIAL AND METHODS We evaluated the expression of AIF-1 in 104
      cases of paired HCC and adjacent non-cancerous liver tissues using
      immunohistochemistry, Western blotting, and qPCR analysis, and sought to
      determine whether its expression was correlated with clinicopathological
      features. In vitro assays, including cell proliferation and migration assays,
      were used to study the effects of AIF-1 knockdown in L02 human hepatocyte, and
      Huh7 and SMMC7721 liver cancer cell lines. RESULTS Expression of AIF-1 was
      increased in HCC compared to adjacent normal liver tissues and was positively
      correlated with median tumor size (p=0.046), number of tumor deposits (p=0.009),
      the Barcelona Clinic Liver Cancer (BCLC) stage (p=0.004), and portal vein tumor
      thrombus (PVTT) (p<0.001). Huh7 and SMMC7721 human HCC cells demonstrated
      upregulated AIF-1 expression compared to normal hepatocytes. Small interfering
      RNA (siRNA)-mediated silencing of AIF-1 expression resulted in a reduction in
      cell proliferation and migration in human HCC cells. CONCLUSIONS These findings
      suggest AIF-1 may have roles as a diagnostic or prognostic biomarker and a
      promising therapeutic target in HCC.

PMID- 30188880
TI  - Notes from the Field: Acquisition of Delamanid Under a Compassionate Use Program
      for Extensively Drug-Resistant Tuberculosis - United States, 2017.

PMID- 30188882
TI  - QuickStats: Repeat* Birth Rates for Teens,? by Urbanization Level of CountyS -
      National Vital Statistics System, 2007-2016.

PMID- 30188881
TI  - Vital Signs: State-Level Variation in Nonfatal and Fatal Cardiovascular Events
      Targeted for Prevention by Million Hearts 2022.
AB  - INTRODUCTION: Despite its preventability, cardiovascular disease remains a
      leading cause of morbidity, mortality, and health care costs in the United
      States. This study describes the burden, in 2016, of nonfatal and fatal
      cardiovascular events targeted for prevention by Million Hearts 2022, a national
      initiative working to prevent one million cardiovascular events during 2017-2021.
      METHODS: Emergency department (ED) visits and hospitalizations were identified
      using Healthcare Cost and Utilization Project databases, and deaths were
      identified using National Vital Statistics System data. Age-standardized Million
      Hearts-preventable event rates and hospitalization costs among adults aged >=18
      years in 2016 are described nationally and across states, as data permit.
      Expected 2017-2021 event totals and hospitalization costs were estimated assuming
      2016 values remain unchanged. RESULTS: Nationally, in 2016, 2.2 million
      hospitalizations (850.9 per 100,000 population) resulting in $32.7 billion in
      costs, and 415,480 deaths (157.4 per 100,000) occurred. Hospitalization and
      mortality rates were highest among men (989.6 and 172.3 per 100,000,
      respectively) and non-Hispanic blacks (211.6 per 100,000, mortality only) and
      increased with age. However, 805,000 hospitalizations and 75,245 deaths occurred
      among adults aged 18-64 years. State-level variation occurred in rates of ED
      visits (from 56.4 [Connecticut] to 274.8 per 100,000 [Kentucky]),
      hospitalizations (484.0 [Wyoming] to 1670.3 per 100,000 [DC]), and mortality
      (111.2 [Vermont] to 267.3 per 100,000 [Mississippi]). Approximately 16.3 million
      events and $173.7 billion in hospitalization costs could occur during 2017-2021
      without preventive intervention. CONCLUSIONS AND IMPLICATIONS FOR PUBLIC HEALTH
      PRACTICE: Million Hearts-preventable events place a considerable health and
      economic burden on the United States. With coordinated efforts, many of these
      events could be prevented in every state to achieve the initiative's goal.

PMID- 30188883
TI  - Assessment of State, Local, and Territorial Zika Planning and Preparedness
      Activities - United States, June 2016-July 2017.
AB  - The emergency response to Zika virus disease required coordinated efforts and
      heightened collaboration among federal, state, local, and territorial public
      health jurisdictions. CDC activated its Emergency Operations Center on January
      21, 2016, with seven task forces to support the national response. The State
      Coordination Task Force, which functions as a liaison between jurisdictions and
      federal operations during a response, coordinated the development of CDC
      Guidelines for Development of State and Local Risk-based Zika Action Plans, which
      included a Zika Preparedness Checklist (1). The checklist summarized
      recommendations covering topics from the seven task forces. In July 2016, CDC's
      Office of Public Health Preparedness and Response (OPHPR) awarded $25 million in
      supplemental funding to 53 jurisdictions (41 states, eight territories, and four
      metropolitan areas) to support Zika preparedness and response activities. In
      December 2016, CDC awarded an additional $25 million to 21 of the 53
      jurisdictions at the greatest risk for seeing Zika in their communities based on
      the presence of the mosquito responsible for spreading Zika, history of local
      transmission, or a high volume of travelers from Zika-affected areas. The
      additional $25 million was part of the $350 million in Zika supplemental funding
      provided to CDC by Congress in 2016* (2,3). Funded jurisdictions reported
      progress through the checklist at five quarterly points throughout the response.
      Data were analyzed to assess planning and response activities. Among the 53
      jurisdictions, the percentage that reported having a Zika virus readiness,
      response, and recovery plan increased from 26% in June 2016 to 64% in July 2017.
      Overall, Zika planning and response activities increased among jurisdictions from
      June 2016 to July 2017. The recent Zika virus outbreak underscores the importance
      of strengthening state, local, and territorial health department capacity for
      rapid response to emerging threats.

PMID- 30188884
TI  - Progress Toward Poliovirus Containment Implementation - Worldwide, 2017-2018.
AB  - Substantial progress has been made since the World Health Assembly (WHA) resolved
      to eradicate poliomyelitis in 1988 (1). Among the three wild poliovirus (WPV)
      types, type 2 (WPV2) was declared eradicated in 2015, and type 3 (WPV3) has not
      been reported since 2012 (1). In 2017 and 2018, only Afghanistan and Pakistan
      have reported WPV type 1 (WPV1) transmission (1). When global eradication of
      poliomyelitis is achieved, facilities retaining poliovirus materials need to
      minimize the risk for reintroduction of poliovirus into communities and
      reestablishment of transmission. Poliovirus containment includes biorisk
      management requirements for laboratories, vaccine production sites, and other
      facilities that retain polioviruses after eradication; the initial milestones are
      for containment of type 2 polioviruses (PV2s). At the 71st WHA in 2018, World
      Health Organization (WHO) Member States adopted a resolution urging acceleration
      of poliovirus containment activities globally, including establishment by the end
      of 2018 of national authorities for containment (NACs) to oversee poliovirus
      containment (2). This report summarizes containment progress since the previous
      report (3) and outlines remaining challenges. As of August 2018, 29 countries had
      designated 81 facilities to retain PV2 materials; 22 of these countries had
      established NACs. Although there has been substantial progress, intensification
      of containment measures is needed.

PMID- 30188885
TI  - Vital Signs: Prevalence of Key Cardiovascular Disease Risk Factors for Million
      Hearts 2022 - United States, 2011-2016.
AB  - INTRODUCTION: Despite decades-long reductions in cardiovascular disease (CVD)
      mortality, CVD mortality rates have recently plateaued and even increased in some
      subgroups, and the prevalence of CVD risk factors remains high. Million Hearts
      2022, a 5-year initiative, was launched in 2017 to address this burden. This
      report establishes a baseline for the CVD risk factors targeted for reduction by
      the initiative during 2017-2021 and highlights recent changes over time. METHODS:
      Risk factor prevalence among U.S. adults was assessed using data from the
      National Health and Nutrition Examination Survey, National Survey on Drug Use and
      Health, and National Health Interview Survey. Multivariate analyses were
      performed to assess differences in prevalence during 2011-2012 and the most
      recent cycle of available data, and across subgroups. RESULTS: During 2013-2014,
      the prevalences of aspirin use for primary and secondary CVD prevention were
      27.4% and 74.9%, respectively, and of statin use for cholesterol management was
      54.5%. During 2015-2016, the average daily sodium intake was 3,535 mg/day and the
      prevalences of blood pressure control, combustible tobacco use, and physical
      inactivity were 48.5%, 22.3%, and 29.1%, respectively. Compared with 2011-2012,
      significant decreases occurred in the prevalences of combustible tobacco use and
      physical inactivity; however, a decrease also occurred for aspirin use for
      primary or secondary prevention. Disparities in risk factor prevalences were
      observed across age groups, genders, and racial/ethnic groups. CONCLUSIONS AND
      IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Millions of Americans have CVD risk
      factors that place them at increased risk for having a cardiovascular event,
      despite the existence of proven strategies for preventing or managing CVD risk
      factors. A concerted effort to implement these strategies will be needed to
      prevent one million acute cardiovascular events during the 5-year initiative.

PMID- 30188886
TI  - Hook length of the bacterial flagellum is optimized for maximal stability of the
      flagellar bundle.
AB  - Most bacteria swim in liquid environments by rotating one or several flagella.
      The long external filament of the flagellum is connected to a membrane-embedded
      basal body by a flexible universal joint, the hook, which allows the transmission
      of motor torque to the filament. The length of the hook is controlled on a
      nanometer scale by a sophisticated molecular ruler mechanism. However, why its
      length is stringently controlled has remained elusive. We engineered and studied
      a diverse set of hook-length variants of Salmonella enterica. Measurements of
      plate-assay motility, single-cell swimming speed, and directional persistence in
      quasi-2D and population-averaged swimming speed and body angular velocity in 3D
      revealed that the motility performance is optimal around the wild-type hook
      length. We conclude that too-short hooks may be too stiff to function as a
      junction and too-long hooks may buckle and create instability in the flagellar
      bundle. Accordingly, peritrichously flagellated bacteria move most efficiently as
      the distance travelled per body rotation is maximal and body wobbling is
      minimized. Thus, our results suggest that the molecular ruler mechanism evolved
      to control flagellar hook growth to the optimal length consistent with efficient
      bundle formation. The hook-length control mechanism is therefore a prime example
      of how bacteria evolved elegant but robust mechanisms to maximize their fitness
      under specific environmental constraints.

PMID- 30188887
TI  - Inter-nucleosomal communication between histone modifications for nucleosome
      phasing.
AB  - Combinatorial effects of epigenetic modifications on transcription activity have
      been proposed as "histone codes". However, it is unclear whether there also exist
      inter-nucleosomal communications among epigenetic modifications at single
      nucleosome level, and if so, what functional roles they play. Meanwhile, how
      clear nucleosome patterns, such as nucleosome phasing and depletion, are formed
      at functional regions remains an intriguing enigma. To address these questions,
      we developed a Bayesian network model for interactions among different histone
      modifications across neighboring nucleosomes, based on the framework of dynamic
      Bayesian network (DBN). From this model, we found that robust inter-nucleosomal
      interactions exist around transcription start site (TSS), transcription
      termination sites (TTS) or around CTCF binding sites; and these inter-nucleosomal
      interactions are often involved in transcription regulation. In addition to these
      general principles, DBN also uncovered a novel specific epigenetic interaction
      between H2A.Z and H4K20me1 on neighboring nucleosomes, involved in nucleosome
      free region (NFR) and nucleosome phasing establishment or maintenance. The level
      of negative correlation between neighboring H2A.Z and H4K20me1 strongly correlate
      with the size of NFR and the strength of nucleosome phasing around TSS. Our study
      revealed inter-nucleosomal communications as important players in signal
      propagation, chromatin remodeling and transcription regulation.

PMID- 30188889
TI  - Network mechanisms underlying the role of oscillations in cognitive tasks.
AB  - Oscillatory activity robustly correlates with task demands during many cognitive
      tasks. However, not only are the network mechanisms underlying the generation of
      these rhythms poorly understood, but it is also still unknown to what extent they
      may play a functional role, as opposed to being a mere epiphenomenon. Here we
      study the mechanisms underlying the influence of oscillatory drive on network
      dynamics related to cognitive processing in simple working memory (WM), and
      memory recall tasks. Specifically, we investigate how the frequency of
      oscillatory input interacts with the intrinsic dynamics in networks of
      recurrently coupled spiking neurons to cause changes of state: the neuronal
      correlates of the corresponding cognitive process. We find that slow
      oscillations, in the delta and theta band, are effective in activating network
      states associated with memory recall. On the other hand, faster oscillations, in
      the beta range, can serve to clear memory states by resonantly driving transient
      bouts of spike synchrony which destabilize the activity. We leverage a recently
      derived set of exact mean-field equations for networks of quadratic integrate-and
      fire neurons to systematically study the bifurcation structure in the
      periodically forced spiking network. Interestingly, we find that the oscillatory
      signals which are most effective in allowing flexible switching between network
      states are not smooth, pure sinusoids, but rather burst-like, with a sharp onset.
      We show that such periodic bursts themselves readily arise spontaneously in
      networks of excitatory and inhibitory neurons, and that the burst frequency can
      be tuned via changes in tonic drive. Finally, we show that oscillations in the
      gamma range can actually stabilize WM states which otherwise would not persist.

PMID- 30188890
TI  - Human rabies in Cote d'Ivoire 2014-2016: Results following reinforcements to
      rabies surveillance.
AB  - In Cote d'Ivoire, rabies is endemic and remains largely uncontrolled. The numbers
      of human exposures and rabies cases are unknown and are probably much higher than
      reported. Data on human rabies cases are collected by the National Institute of
      Public Health (NIPH) Anti-rabies Center in Abidjan through a network of 28 NIPH
      local units, which cover the population of the entire country. During 2014, the
      NIPH initiated a program to reinforce the human rabies surveillance system in
      those 28 NIPH local units, with specific goals of improving the infrastructure,
      training, communication, and government involvement. Here, we report the progress
      and findings during 2014-2016. The reinforced system recorded 50 cases of human
      rabies (15-18 cases/year; annual incidence = 0.06-0.08 per 100,000) and more than
      30,000 animal exposures (annual incidence = 41.8-48.0 per 100,000). Almost one
      half of the human rabies cases were in children <=15 years old. All were fatal
      and dog bites were the most common route by which rabies virus was transmitted.
      In the 32 cases where samples of sufficient quality for analysis were available,
      rabies was confirmed by reverse transcription-polymerase chain reaction RT-PCR.
      Post-exposure prophylaxis with rabies vaccine was administered to all animal
      exposure victims presenting at the NIPH local units, although only about 57%
      completed the full immunization schedule. All available reports were provided by
      the NIPH local units, indicating effective communication between them and the
      NIPH Anti-rabies Center. These findings indicate that the reinforcements resulted
      in highly specific detection of human rabies, provided detailed epidemiological
      data about these cases, and improved estimates of animal exposure numbers. These
      represent substantial advances, but further improvements to the surveillance
      system are needed to increase disease awareness and capture cases that are
      currently missed by the system. In the future, better communication between local
      health centers and the NIPH units, surveillance at the local health center level,
      and increased veterinarian engagement will help provide a more complete picture
      of the rabies burden in Cote d'Ivoire.

PMID- 30188888
TI  - Somatic inactivating PTPRJ mutations and dysregulated pathways identified in
      canine malignant melanoma by integrated comparative genomic analysis.
AB  - Canine malignant melanoma, a significant cause of mortality in domestic dogs, is
      a powerful comparative model for human melanoma, but little is known about its
      genetic etiology. We mapped the genomic landscape of canine melanoma through
      multi-platform analysis of 37 tumors (31 mucosal, 3 acral, 2 cutaneous, and 1
      uveal) and 17 matching constitutional samples including long- and short-insert
      whole genome sequencing, RNA sequencing, array comparative genomic hybridization,
      single nucleotide polymorphism array, and targeted Sanger sequencing analyses. We
      identified novel predominantly truncating mutations in the putative tumor
      suppressor gene PTPRJ in 19% of cases. No BRAF mutations were detected, but
      activating RAS mutations (24% of cases) occurred in conserved hotspots in all
      cutaneous and acral and 13% of mucosal subtypes. MDM2 amplifications (24%) and
      TP53 mutations (19%) were mutually exclusive. Additional low-frequency recurrent
      alterations were observed amidst low point mutation rates, an absence of
      ultraviolet light mutational signatures, and an abundance of copy number and
      structural alterations. Mutations that modulate cell proliferation and cell cycle
      control were common and highlight therapeutic axes such as MEK and MDM2
      inhibition. This mutational landscape resembles that seen in BRAF wild-type and
      sun-shielded human melanoma subtypes. Overall, these data inform biological
      comparisons between canine and human melanoma while suggesting actionable targets
      in both species.

PMID- 30188891
TI  - Improving systematic rabies surveillance in Cameroon: A pilot initiative and
      results for 2014-2016.
AB  - Canine rabies is endemic in Cameroon, but human rabies exposures and cases are
      likely underreported because of inadequate surveillance. In 2014, the
      surveillance network in the West region of Cameroon was reinforced by introducing
      a new anti-rabies center, a framework for data collection and evaluation,
      provisions for sample collecting and laboratory confirmation, and training for
      health professionals. The objective of this observational cohort study was to
      describe the incidence and characteristics of reported exposures and human and
      animal rabies cases following this reinforcement of the existing rabies
      surveillance system. The surveillance network consisted of local, regional, and
      national health and veterinary authorities in 11 of the 20 West region districts,
      and was completely integrated within the existing national rabies surveillance
      network. Animal exposures and suspected rabies exposures, the suspected rabid
      animals involved, and laboratory confirmation of human and animal rabies cases
      were recorded in a centralized information database. Between January 2014 and
      June 2016, the network recorded 1340 animal exposure cases for an overall
      incidence rate of 38.2 animal exposures per 100,000 people, four confirmed rabies
      positive animals, and one confirmed human rabies case out of four clinically
      suspected cases. In contrast, 62 animal exposures and an overall incidence rate
      of 6.1 exposures per 100,000 people were reported for the West region districts
      not participating in the reinforced surveillance. Of the 925 animal exposure
      victims for whom a detailed case report form was completed, 703 were considered
      to be at risk of rabies and only 428 (61%) of these received any post-exposure
      prophylaxis in the form of rabies vaccine. Obstacles encountered within the
      network included low rates of animal sample submission and animal follow-up by
      veterinarians. Reinforced rabies surveillance in the West region of Cameroon has
      provided the most accurate estimate of the region's disease and exposure burdens
      to date, and indicates that animal exposures are substantially underreported. The
      reinforced network also signaled that greater access to post-exposure prophylaxis
      is needed. Integration of regions not covered by the surveillance network and
      efforts to improve engagement of veterinary services will be needed to reveal the
      true burden of rabies in Cameroon.

PMID- 30188892
TI  - FGF-induced Pea3 transcription factors program the genetic landscape for cell
      fate determination.
AB  - FGF signaling is a potent inducer of lacrimal gland development in the eye,
      capable of transforming the corneal epithelium into glandular tissues. Here, we
      show that genetic ablation of the Pea3 family of transcription factors not only
      disrupted the ductal elongation and branching of the lacrimal gland, but also
      biased the lacrimal gland epithelium toward an epidermal cell fate. Analysis of
      high-throughput gene expression and chromatin immunoprecipitation data revealed
      that the Pea3 genes directly control both the positive and negative feedback
      loops of FGF signaling. Importantly, Pea3 genes are also required to suppress
      aberrant Notch signaling which, if gone unchecked, can compromise lacrimal gland
      development by preventing the expression of both Sox and Six family genes. These
      results demonstrate that Pea3 genes are key FGF early response transcriptional
      factors, programing the genetic landscape for cell fate determination.

PMID- 30188894
TI  - Recent advances in the Giardia-host relationship reveal danger lurking behind the
      smile.

PMID- 30188893
TI  - Whole exome sequencing of ENU-induced thrombosis modifier mutations in the mouse.
AB  - Although the Factor V Leiden (FVL) gene variant is the most prevalent genetic
      risk factor for venous thrombosis, only 10% of FVL carriers will experience such
      an event in their lifetime. To identify potential FVL modifier genes contributing
      to this incomplete penetrance, we took advantage of a perinatal synthetic lethal
      thrombosis phenotype in mice homozygous for FVL (F5L/L) and haploinsufficient for
      tissue factor pathway inhibitor (Tfpi+/-) to perform a sensitized dominant ENU
      mutagenesis screen. Linkage analysis conducted in the 3 largest pedigrees
      generated from the surviving F5L/L Tfpi+/- mice ('rescues') using ENU-induced
      coding variants as genetic markers was unsuccessful in identifying major
      suppressor loci. Whole exome sequencing was applied to DNA from 107 rescue mice
      to identify candidate genes enriched for ENU mutations. A total of 3,481
      potentially deleterious candidate ENU variants were identified in 2,984 genes.
      After correcting for gene size and multiple testing, Arl6ip5 was identified as
      the most enriched gene, though not reaching genome-wide significance. Evaluation
      of CRISPR/Cas9 induced loss of function in the top 6 genes failed to demonstrate
      a clear rescue phenotype. However, a maternally inherited (not ENU-induced) de
      novo mutation (Plcb4R335Q) exhibited significant co-segregation with the rescue
      phenotype (p = 0.003) in the corresponding pedigree. Thrombosis suppression by
      heterozygous Plcb4 loss of function was confirmed through analysis of an
      independent, CRISPR/Cas9-induced Plcb4 mutation (p = 0.01).

PMID- 30188896
TI  - Bolstering human rabies surveillance in Africa is crucial to eliminating canine
      mediated rabies.

PMID- 30188895
TI  - The conserved protective cyclic AMP-phosphodiesterase function PDE4B is expressed
      in the adenoma and adjacent normal colonic epithelium of mammals and silenced in
      colorectal cancer.
AB  - Conservation over three mammalian genera-the mouse, rat, and human-has been found
      for a subset of the transcripts whose level differs between the adenoma and
      normal epithelium of the colon. Pde4b is one of the triply conserved transcripts
      whose level is enhanced both in the colonic adenoma and in the normal colonic
      epithelium, especially adjacent to adenomas. It encodes the phosphodiesterase
      PDE4B, specific for cAMP. Loss of PDE4B function in the ApcMin/+ mouse leads to a
      significant increase in the number of colonic adenomas. Similarly, Pde4b
      deficient ApcMin/+ mice are hypersensitive to treatment by the inflammatory agent
      DSS, becoming moribund soon after treatment. These observations imply that the
      PDE4B function protects against ApcMin-induced adenomagenesis and inflammatory
      lethality. The paradoxical enhancement of the Pde4b transcript in the adenoma
      versus this inferred protective function of PDE4B can be rationalized by a
      feedback model in which PDE4B is first activated by early oncogenic stress
      involving cAMP and then, as reported for frank human colon cancer, inactivated by
      epigenetic silencing.

PMID- 30188898
TI  - Burden of leishmaniasis in Brazil and federated units, 1990-2016: Findings from
      Global Burden of Disease Study 2016.
AB  - BACKGROUND: The study presents estimates for the burden of visceral leishmaniasis
      (VL) and cutaneous and mucocutaneous leishmaniasis (CML) in Brazil and its 27
      federated units using data from the Global Burden of Disease Study (GBD) 2016.
      METHODOLOGY: We report the incidence, years of life lost (YLL), years lived with
      disability (YLD), and disability-adjusted life years (DALY) for leishmaniasis in
      Brazil from 1990 to 2016. The metrics are presented as age-standardized rates per
      100,000 inhabitants with their respective uncertainty intervals (95%UI) and
      relative percentages of change. PRINCIPAL FINDINGS: The age-standardized
      incidence rate of leishmaniasis decreased 48.5% from 1990 (71.0, 95%UI 24.3
      150.7) to 2016 (36.5, 95%UI 24.7-50.9), whereas the age-standardized DALY
      increased 83.6% over the studied period from 12.2 (95%UI 7.9-18.8) to 22.4 (95%UI
      13.3-36.2). The age-standardized incidence rate and YLL for VL increased by 52.9%
      and 108% from 1990 to 2016, respectively. Considering CML, the age-standardized
      incidence rate and YLD decreased by 51% and 31.8% respectively for the same
      period. For VL, similar profiles for male and female were observed, with YLL and
      DALY increasing over time; with males presenting slightly higher values. The
      highest YLL rates were among "under 1-year old" children, which increased 131.2%
      from 1990 to 2016. Regarding CML, the highest values of YLD and DALY were
      verified among males, and YLD values showed a similar profile, with rates
      increasing with age. The VL burden increased in some states in the Northeast and
      Southeast regions and decreased for CML in some Northern states. CONCLUSION: The
      increase of VL burden over the study period might be associated with the
      difficulties in controlling the disease spread. Information regarding the weight
      of VL and CML, including the death and disability tolls that they cause,
      highlights the impact of these neglected diseases on public health and the
      importance of effective prevention and treatment.

PMID- 30188897
TI  - Detecting past and ongoing natural selection among ethnically Tibetan women at
      high altitude in Nepal.
AB  - Adaptive evolution in humans has rarely been characterized for its whole set of
      components, i.e. selective pressure, adaptive phenotype, beneficial alleles and
      realized fitness differential. We combined approaches for detecting polygenic
      adaptations and for mapping the genetic bases of physiological and fertility
      phenotypes in approximately 1000 indigenous ethnically Tibetan women from Nepal,
      adapted to high altitude. The results of genome-wide association analyses and
      tests for polygenic adaptations showed evidence of positive selection for alleles
      associated with more pregnancies and live births and evidence of negative
      selection for those associated with higher offspring mortality. Lower hemoglobin
      level did not show clear evidence for polygenic adaptation, despite its strong
      association with an EPAS1 haplotype carrying selective sweep signals.

PMID- 30188899
TI  - Spinal muscular atrophy within Amish and Mennonite populations: Ancestral
      haplotypes and natural history.
AB  - We correlate chromosome 5 haplotypes and SMN2 copy number with disease expression
      in 42 Mennonite and 14 Amish patients with spinal muscular atrophy (SMA). A
      single haplotype (A1) with 1 copy of SMN2 segregated among all Amish patients.
      SMN1 deletions segregated on four different Mennonite haplotypes that carried 1
      (M1a, M1b, M1c) or 2 (M2) copies of SMN2. DNA microsatellite and microarray data
      revealed structural similarities among A1, M1a, M1b, and M2. Clinical data were
      parsed according to both SMN1 genotype and SMN2 copy number (2 copies, n = 44; 3
      copies, n = 9; or 4 copies, n = 3). No infant with 2 copies of SMN2 sat
      unassisted. In contrast, all 9 Mennonites with the M1a/M2 genotype (3 copies of
      SMN2) sat during infancy at a median age of 7 months, and 5 (56%) walked and
      dressed independently at median ages of 18 and 36 months, respectively. All are
      alive at a median age of 11 (range 2-31) years without ventilatory support. Among
      13 Amish and 26 Mennonite patients with 2 copies of SMN2 who did not receive
      feeding or ventilatory support, A1/A1 as compared to M1a/M1a genotype was
      associated with earlier clinical onset (p = 0.0040) and shorter lifespan (median
      survival 3.9 versus 5.7 months, p = 0.0314). These phenotypic differences were
      not explained by variation in SMN1 deletion size or SMN2 coding sequence, which
      were conserved across haplotypes. Distinctive features of SMA within Plain
      communities provide a population-specific framework to study variations of
      disease expression and the impact of disease-modifying therapies administered
      early in life.

PMID- 30188900
TI  - Is it feasible to use smartphone images to perform telediagnosis of different
      stages of occlusal caries lesions?
AB  - The purpose of this study was to compare the performance of two different models
      of smartphone and a conventional camera with that of direct clinical examination
      in detecting caries lesions at different stages of progression in deciduous
      molars. The photographic equipment consisted of two smartphones (iPhone and Nexus
      4) and a conventional macro camera setup. First, in the laboratory phase of the
      study, we compared the images of 20 exfoliated primary teeth having caries
      lesions at different stages. Then, in the clinical phase of the study, the images
      of 119 primary molars from fifteen children (3 to 6 years old) were used. All of
      the photographic images were taken using the previously described devices. In
      both groups, two examiners, blinded to the photographic equipment used, assessed
      the images independently on a computer screen, and classified them according to
      the International Caries Detection and Assessment System (ICDAS). The teeth were
      then examined directly by two other experienced examiners, and the consensus
      reached was considered the reference standard. Parameters of validity, such as
      percentage of correct answers, agreement with the reference standard,
      sensitivity, specificity and inter-examiner agreement (using the weighted kappa
      test) were calculated. The examiners performed similarly in both in vitro and in
      vivo studies. Inter-examiner reliability was approximately 0.7 for all the
      devices in the laboratory setting, and for the macro camera photography system in
      the clinical setting, but it was approximately 0.9 for the iPhone and Nexus
      images taken in vivo. With regard to the percentage of correct answers, the
      highest values were observed for sound and extensive caries lesions in both
      laboratory and clinical settings. The percentage of correct answers for initial
      and moderate lesions was particularly low in the clinical evaluation,
      irrespective of the camera devices used. Therefore, we concluded that
      photographic diagnosis using smartphone images is feasible and accurate for
      distinguishing sound tooth surfaces from extensive caries lesions; however,
      photographic images are not a good method for accurately detecting initial and
      moderate caries lesions.

PMID- 30188901
TI  - A fully autonomous terrestrial bat-like acoustic robot.
AB  - Echolocating bats rely on active sound emission (echolocation) for mapping novel
      environments and navigating through them. Many theoretical frameworks have been
      suggested to explain how they do so, but few attempts have been made to build an
      actual robot that mimics their abilities. Here, we present the 'Robat'-a fully
      autonomous bat-like terrestrial robot that relies on echolocation to move through
      a novel environment while mapping it solely based on sound. Using the echoes
      reflected from the environment, the Robat delineates the borders of objects it
      encounters, and classifies them using an artificial neural-network, thus creating
      a rich map of its environment. Unlike most previous attempts to apply sonar in
      robotics, we focus on a biological bat-like approach, which relies on a single
      emitter and two ears, and we apply a biological plausible signal processing
      approach to extract information about objects' position and identity.

PMID- 30188902
TI  - Feasibility and initial outcomes of a multifaceted prevention programme of
      melioidosis in diabetic patients in Ubon Ratchathani, northeast Thailand.
AB  - BACKGROUND: Melioidosis is an infection caused by Burkholderia pseudomallei, a
      Gram-negative bacillus found in soil and water. Diabetes mellitus is the most
      important risk factor for melioidosis. The recommendations for disease prevention
      include avoiding direct contact with soil and water, and drinking only boiled or
      bottled water. METHODS: A prospective intervention study was conducted to
      evaluate the feasibility and behavioural outcomes of a multifaceted prevention
      programme for melioidosis. Participants were diabetic adults in Ubon Ratchathani,
      northeast Thailand. Ten behavioural support groups consisting of 6 to 10
      participants per group were conducted. Twelve behaviour change techniques were
      used: information about health consequences, credible source, adding objects to
      the environment, reconstructing the physical environment, instruction on how to
      perform a behaviour, demonstration of the behaviour, commitment, prompts/cues,
      self-monitoring of behaviour, goal setting, feedback on behaviour, and social
      support, and their feasibilities evaluated. RESULTS: There were 70 participants,
      of median age 59 years and 52 (74%) were female. Participants found the
      intervention beneficial, interesting and engaging. Participants indicated that
      they liked to watch videos with information about melioidosis delivered by local
      doctors and patients who survived melioidosis, and videos showing use of over-the
      knee boots by local farmers. Participants felt engaged in the sessions that
      trialed protective gear and that made calendars with individual photographs and
      self-pledges as a reminder tool. The proportions of participants reporting that
      they always wore boots while working in rice fields increased from 30% (10/33) to
      77% (28/37, p = 0.04), and that they drank only boiled or bottle water increased
      from 43% (30/70) to 86% (59/69, p<0.001) at 6 months post intervention.
      CONCLUSION: The programme is highly acceptable to participants, and can support
      behaviour change. Policy makers should consider implementing the programme in
      areas where melioidosis is endemic. Making calendars with individual photographs
      and self-pledges as a reminder tool could be powerful in behaviour change
      interventions, and further research on this component is needed.

PMID- 30188903
TI  - Patching a leak in an R1 university gateway STEM course.
AB  - A cognitively intensive companion service course has been introduced to the main
      fall general chemistry class at Cornell University. For years 2015 and 2016,
      priority students (those from groups under-represented and economically
      disadvantaged) show respectively improvement of +0.67 and +0.51 standard
      deviations in final course grade compared to priority students not in the
      program. Non-priority students show respectively a +0.66 and +0.62 standard
      deviation improvement. Progressive improvement (as measured by higher than
      expected Final Exam scores than what would have been expected solely from a given
      student's earlier Exam 1 score) demonstrates conclusively the service course's
      role in the enhanced outcomes. Progressive retention (as measured by the
      following year fall semester's organic chemistry exam scores compared to what
      would have been expected based on a given student's general chemistry final exam
      score) demonstrates that, on the average, the earlier observed progressive
      improvement is significantly retained in a chemistry course one year later.
      Preliminary retention statistics suggest a significant increase in first year to
      second year retention. A meta analysis of results from previously reported
      chemistry service courses indicate that such performance gains are difficult to
      achieve and hence common elements of the few effective programs may be of high
      value to the STEM education community.

PMID- 30188904
TI  - Typhoid fever in Santiago, Chile: Insights from a mathematical model utilizing
      venerable archived data from a successful disease control program.
AB  - Typhoid fever is endemic in many developing countries. In the early 20th century,
      newly industrializing countries including the United States successfully
      controlled typhoid as water treatment (chlorination/sand filtration) and improved
      sanitation became widespread. Enigmatically, typhoid remained endemic through the
      1980s in Santiago, Chile, despite potable municipal water and widespread
      household sanitation. Data were collected across multiple stages of endemicity
      and control in Santiago, offering a unique resource for gaining insight into
      drivers of transmission in modern settings. We developed an individual-based
      mathematical model of typhoid transmission, with model components including
      distinctions between long-cycle and short-cycle transmission routes. Data used to
      fit the model included the prevalence of chronic carriers, seasonality,
      longitudinal incidence, and age-specific distributions of typhoid infection and
      disease. Our model captured the dynamics seen in Santiago across endemicity,
      vaccination, and environmental control. Both vaccination and diminished exposure
      to seasonal amplified long-cycle transmission contributed to the observed
      declines in typhoid incidence, with the vaccine estimated to elicit herd effects.
      Vaccines are important tools for controlling endemic typhoid, with even limited
      coverage eliciting herd effects in this setting. Removing the vehicles
      responsible for amplified long-cycle transmission and assessing the role of
      chronic carriers in endemic settings are additional key elements in designing
      programs to achieve accelerated control of endemic typhoid.

PMID- 30188905
TI  - Phylogenomic analysis unravels evolution of yellow fever virus within hosts.
AB  - The yellow fever virus (YFV) recently reemerged in the large outbreaks in Africa
      and Brazil, and the first imported patients into Asia have recalled the concerns
      of YFV evolution. Here we show phylogenomics of YFV with serial clinical samples
      of the 2016 YFV infections. Phylogenetics exhibited that the 2016 strains were
      close to Angola 1971 strains and only three amino acid changes presented new to
      other lineages. Deep sequencing of viral genomes discovered 101 intrahost single
      nucleotide variations (iSNVs) and 234 single nucleotide polymorphisms (SNPs).
      Analysis of iSNV distribution and mutated allele frequency revealed that the
      coding regions were under purifying selection. Comparison of the evolutionary
      rates estimated by iSNV and SNP showed that the intrahost rate was ~2.25 times
      higher than the epidemic rate, and both rates were higher than the long-term YFV
      substitution rate, as expected. In addition, the result also hinted that short
      viremia duration of YFV might further hinder the evolution of YFV.

PMID- 30188906
TI  - Quality and resource efficiency in hospital service provision: A geoadditive
      stochastic frontier analysis of stroke quality of care in Germany.
AB  - We specify a Bayesian, geoadditive Stochastic Frontier Analysis (SFA) model to
      assess hospital performance along the dimensions of resources and quality of
      stroke care in German hospitals. With 1,100 annual observations and data from
      2006 to 2013 and risk-adjusted patient volume as output, we introduce a
      production function that captures quality, resource inputs, hospital inefficiency
      determinants and spatial patterns of inefficiencies. With high relevance for
      hospital management and health system regulators, we identify performance
      improvement mechanisms by considering marginal effects for the average hospital.
      Specialization and certification can substantially reduce mortality. Regional and
      hospital-level concentration can improve quality and resource efficiency.
      Finally, our results demonstrate a trade-off between quality improvement and
      resource reduction and substantial regional variation in efficiency.

PMID- 30188907
TI  - Indirect (implicit) and direct (explicit) self-esteem measures are virtually
      unrelated: A meta-analysis of the initial preference task.
AB  - BACKGROUND: The initial preference task (IPT) is an implicit measure that has
      featured prominently in the literature and enjoys high popularity because it
      offers to provide an unobtrusive and objective assessment of self-esteem that is
      easy to administer. However, its use for self-esteem assessment may be limited
      because of weak associations with direct personality measures. Moreover,
      moderator effects of sample- and study-related variables need investigation to
      determine the value of IPT-based assessments of self-esteem. METHODS:
      Conventional and grey-literature database searches, as well as screening of
      reference lists of obtained articles, yielded a total of 105 independent healthy
      adult samples (N = 17,777) originating from 60 studies. Summary effect estimates
      and subgroup analyses for potential effect moderators (e.g., administration
      order, algorithm, rating type) were calculated by means of meta-analytic random-
      and mixed-effects models. Moreover, we accounted for potential influences of
      publication year, publication status (published vs. not), and participant sex in
      a weighted stepwise hierarchical multiple meta-regression. We tested for
      dissemination bias through six methods. RESULTS: There was no noteworthy
      correlation between IPT-based implicit and explicit self-esteem (r = .102),
      indicating conceptual independence of these two constructs. Effects were stronger
      when the B-algorithm was used for calculation of IPT-scores and the IPT was
      administered only once, whilst all other moderators did not show significant
      influences. Regression analyses revealed a somewhat stronger (albeit non
      significant) effect for men. Moreover, there was no evidence for dissemination
      bias or a decline effect, although effects from published studies were
      numerically somewhat stronger than unpublished effects. DISCUSSION: We show that
      there is no noteworthy association between IPT-based implicit and explicit self
      esteem, which is broadly consistent with dual-process models of implicit and
      explicit evaluations on the one hand, but also casts doubt on the suitability of
      the IPT for the assessment of implicit self-esteem on the other hand.

PMID- 30188908
TI  - One-pass-throw-away learning for cybersecurity in streaming non-stationary
      environments by dynamic stratum network.
AB  - Throughout recent times, cybersecurity problems have occurred in various business
      applications. Although previous researchers proposed to cope with the occurrence
      of cybersecurity issues, their methods repeatedly replicated the training
      processes for several times to classify datasets of these problems in streaming
      non-stationary environments. In dynamic environments, the conventional methods
      possibly deteriorate the adaptive solution to prevent these issues. This research
      proposes a one-pass-throw-away learning using the dynamical structure of the
      network to solve these problems in dynamic environments. Furthermore, to speed up
      the computational time and to maintain a minimum space complexity for streaming
      data, the new concepts of learning in forms of recursive functions were
      introduced. The information gain-based feature selection was also applied to
      reduce the learning time during the training process. The experimental results
      signified that the proposed algorithm outperformed the others in incremental-like
      and online ensemble learning algorithms in terms of classification accuracy,
      space complexity, and computational time.

PMID- 30188909
TI  - Alterations of the nigrostriatal pathway in a 6-OHDA rat model of Parkinson's
      disease evaluated with multimodal MRI.
AB  - Parkinson's disease is characterized by neurodegeneration of the dopaminergic
      neurons in the substantia nigra pars compacta. The 6-hydroxydopamine (6-OHDA) rat
      model has been used to study neurodegeneration in the nigro-striatal dopaminergic
      system. The goal of this study was to evaluate the reliability of diffusion MRI
      and resting-state functional MRI biomarkers in monitoring neurodegeneration in
      the 6-OHDA rat model assessed by quantitative histology. We performed a
      unilateral injection of 6-OHDA in the striatum of Sprague Dawley rats to produce
      retrograde degeneration of the dopamine neurons in the substantia nigra pars
      compacta. We carried out a longitudinal study with a multi-modal approach
      combining structural and functional MRI together with quantitative histological
      validation to follow the effects of the lesion. Functional and structural
      connectivity were assessed in the brain of 6-OHDA rats and sham rats (NaCl
      injection) at 3 and 6 weeks post-lesioning using resting-state functional MRI and
      diffusion-weighted. Our results showed (i) increased functional connectivity in
      ipsi- and contra-lesioned regions of the cortico-basal ganglia network pathway
      including the motor cortex, the globus pallidus, and the striatum regions at 3
      weeks; (ii) increased fractional anisotropy (FA) in the ipsi- and contralateral
      striatum of the 6-OHDA group at 3 weeks, and increased axial diffusivity (AD) and
      mean diffusivity in the ipsilateral striatum at 6 weeks; (iii) a trend for
      increased FA in both substantia nigra of the 6-OHDA group at 3 weeks. Optical
      density measurements of tyrosine-hydroxylase (TH) staining of the striatum showed
      good correlations with the FA and AD measurements in the striatum. No
      correlations were found between the number of TH-stained dopaminergic neurons and
      MRI measurements in the substantia nigra. This study suggested that (i) FA and AD
      were reliable biomarkers to evaluate neurodegeneration in the cortico-basal
      ganglia network of the 6-OHDA model, (ii) diffusion MRI and resting-state
      functional MRI (rsfMRI) were not sensitive enough to detect changes in the
      substantia nigra in this model.

PMID- 30188910
TI  - High frequency electrical stimulation induces a long-lasting enhancement of event
      related potentials but does not change the perception elicited by intra-epidermal
      electrical stimuli delivered to the area of increased mechanical pinprick
      sensitivity.
AB  - High frequency electrical stimulation (HFS) of the skin induces increased
      pinprick sensitivity in the surrounding unconditioned skin. The aim of the
      present study was to investigate the contribution of A-fiber nociceptors to this
      increased pinprick sensitivity. For this we assessed if the perception and brain
      responses elicited by low-intensity intra-epidermal electrical stimulation (IES),
      a method preferentially activating Adelta-fiber nociceptors, are increased in the
      area of HFS-induced increased pinprick sensitivity. HFS was delivered to one of
      the two forearms of seventeen healthy volunteers. Mechanical pinprick stimulation
      and IES were delivered at both arms before HFS (T0), 20 minutes after HFS (T1)
      and 45 minutes after HFS (T2). In all participants, HFS induced an increase in
      pinprick perception at the HFS-treated arm, adjacent to the site of HFS. This
      increase was significant at both T1 and T2. HFS did not affect the percept
      elicited by IES, but did enhance the magnitude of the N2 wave of IES-evoked brain
      potentials, both at T1 and at T2. Our results show that HFS induces a long
      lasting enhancement of the N2 wave elicited by IES in the area of secondary
      hyperalgesia, indicating that HFS enhances the responsiveness of the central
      nervous system to nociceptive A-fiber input. However, we found no evidence that
      HFS affects the perception elicited by IES, which may suggest that the population
      of nociceptors that mediate the perception elicited by IES do not contribute to
      HFS-induced increased pinprick sensitivity.

PMID- 30188911
TI  - Molecular characterization of Carbapenem resistant Escherichia coli recovered
      from a tertiary hospital in Lebanon.
AB  - The emergence of carbapenem resistant Escherichia coli represents a serious
      public health concern. This study investigated the resistome, virulence, plasmids
      content and clonality of 27 carbapenem resistant E. coli isolated from 27
      hospitalized patients at the American University of Beirut Medical Center (AUBMC)
      in Lebanon between 2012 and 2016. Whole-genome sequencing (WGS) data were used to
      identify resistance determinants. Multilocus sequence typing (MLST), pulsed field
      gel electrophoresis (PFGE), phylogenetic grouping and PCR-based replicon typing
      (PBRT) were also performed. The 27 isolates were distributed into 15 STs, of
      which ST405 (14.8%; n = 4) was the most prevalent. All of the 27 isolates were
      carbapenem resistant and 20 (74%) were extended-spectrum beta-lactamase (ESBL)
      gene carriers. The predominant detected carbapenemases were blaOXA-48 (48.1%; n =
      13) and blaOXA-181 (7.4%; n = 2), for the ESBLs it was blaCTX-M-15 (55.6%; n =
      15) and blaCTX-M-24 (18.5%; n = 5), and for the AmpC-type beta-lactamases, blaCMY
      42 (40.7%; n = 11) and blaCMY-2 (3.7%; n = 1). Thirteen replicons were identified
      among the 27 E. coli isolates including: IncL/M, IncFIA, IncFIB, IncFII, IncI1,
      and IncX3. PFGE revealed a high genetic diversity with the 27 isolates being
      grouped in 21 different pulsotypes. SNPs analysis and PFGE showed a possible
      clonal dissemination of ST405, ST1284, ST354 and ST410 and the dominance of
      certain STs, monitoring of which could help in elucidating routes of
      transmission. This study represents the first WGS-based in depth analysis of the
      resistomes and mobilomes of carbapenem resistant E. coli in Lebanon.

PMID- 30188912
TI  - Long term outcomes of cluster randomized trial to improve cardiovascular health
      at population level: The Cardiovascular Health Awareness Program (CHAP).
AB  - STUDY QUESTION: The Cardiovascular Health Awareness Program (CHAP) cardiovascular
      risk reduction program consisted of sessions run by local volunteers in local
      pharmacies during which cardiovascular risk was assessed, healthy lifestyle and
      preventive care was promoted, and the participants were oriented to local
      resources to support changes in modifiable risk factors. A clustered randomized
      trial implemented in September 2006 across 39 communities targeting community
      dwelling individuals 65 years and older showed a significant reduction in
      hospitalization one year after its implementation (rate ratio of 91 [95%
      confidence interval (CI): 86%-97%]). This study explores the impact of CHAP in
      the first five years. METHODS: Using health administrative data housed at the
      Institute for Clinical Evaluative Sciences, we established a closed cohort
      consisting of all individuals eligible in these communities at the study onset
      whom we followed over time. We assessed hospitalizations and survival using a
      negative binomial model for count data and Cox regression to assess time to first
      event, accounting for the clustered design. The primary outcome was the rate of
      cardiovascular-related hospitalizations defined as congestive heart failure,
      stroke or acute myocardial infarction. RESULTS: Most estimates pointed to an
      advantage for the intervention arm, but only all-cause mortality reached
      statistical significance (hazard ratio [95% CI] = 0.955 [0.914-0.999]). The
      hospitalization cardiovascular-related hospitalization rate ratio was (0.958, 95%
      CI: 0.898-1.022) in favour of the intervention communities, translating to an
      estimated 408 averted hospitalizations over the five-year period. There was no
      evidence of the effect of time from start of intervention. CONCLUSIONS: The
      consistent direction of the outcomes in favour of the intervention arms suggests
      that CHAP likely had a meaningful impact on reducing cardiovascular-related
      morbidity and mortality. Given the low cost of the intervention, further
      development of CHAP should be pursued.

PMID- 30188913
TI  - Novel isothiacalothrixin B analogues exhibit cytotoxic activity on human colon
      cancer cells in vitro by inducing irreversible DNA damage.
AB  - Preliminary cytotoxic analysis of sulphur containing isosteric analogues of
      calothrixin B identified the useful anti-tumour activity of
      thia/isothiacalothrixin B which necessitated it's biological evaluation in colon
      and lung cancer cell lines. The isothia analogues induced cytotoxicity of HCT116
      in a time-dependent manner and inhibited the clonogenic survival of HCT116 and
      NCI-H460 cells in a dose-dependent manner comparable to the standard anti-cancer
      drug camptothecin. Herein employing flow cytometry, we demonstrate that
      isothiacalothrixin B analogues inhibited proliferation of colon cancer cells by
      the arrest of cells in S and G2/M phases over a period of 48 hours at a
      concentration of 5 MUM. Our results also suggest that the cytotoxicity of thia
      analogues of calothrixin B is partially mediated by induction of cellular DNA
      strand breaks. The UV-Vis spectroscopic studies with CT-DNA revealed groove
      binding for calothrixin B and its thia analogues wherein subsequent in silico
      molecular modelling studies indicated preferential binding to the AT-rich regions
      of minor groove of DNA. Furthermore, thiacalothrixin B caused transcriptional
      activation of p21waf1/cip1 promoter and upregulation of its protein levels
      independent of p53. The induction of DNA damage response pathway leads to
      apoptosis in isothiacalothrixin B but not in thiacalothrixin B treated cells. The
      isothia analogues SCAB 4 induced DNA strand breaks and cell cycle arrest even
      after treatment for a short period (i.e., 4 hours) and the cell cycle effects
      were irreversible. For the first time, this study provides detailed cellular
      effects on the potential use of isothiacalothrixin B analogues as cytotoxic
      agents.

PMID- 30188915
TI  - Evaluation of various kinetic parameters of CA-125 in patients with advanced
      stage ovarian cancer undergoing neoadjuvant chemotherapy.
AB  - Various kinetic parameters of serum CA-125 have been reported to have better
      correlation with outcomes for patients treated with neoadjuvant chemotherapy
      (NAC). This study aimed to compare the available kinetic parameters of serum CA
      125 in an external cohort of advanced-stage ovarian cancer. Using the cancer
      registry databases from the Yonsei Cancer Hospital, we retrospectively reviewed
      210 patients with advanced-stage ovarian cancer, treated with NAC followed by
      interval debulking surgery. We compared area under the receiver-operating
      characteristics curves (AUCs), false negative rate, and negative predictive value
      (NPV) using 10 different models for optimal cytoreduction and platinum
      resistance. In addition, we compared incremental AUC for progression-free
      survival (PFS) and overall survival (OS). No gross residual tumor was observed in
      37.0% and residual tumors <1 cm in 82.2% of patients. No model using CA-125
      kinetic parameters had an AUC higher than >0.6 for predicting optimal
      cytoreduction. After adjusting for age, BMI, disease stage, and histologic
      subtypes, all models had an AUC >0.70 for predicting platinum resistance.
      However, no model had a high enough NPV (highest value = 82.0%) to avoid
      chemotherapy futility. For survival outcomes, no model had an incremental AUC
      >0.70 for predicting either PFS or OS. None of the proposed serum CA-125 kinetic
      parameters showed high accuracy in predicting optimal cytoreduction, platinum
      resistance, or survival in patients receiving NAC. For advanced-stage ovarian
      cancer treated with NAC, there is a need to discover reliable biomarkers to
      better stratify patient response groups for optimal treatment decision-making.

PMID- 30188917
TI  - Novel extraction technique of retained pacemaker and defibrillator lead during
      heart transplantation.
AB  - BACKGROUND: Removal of cardiac implantable electronic devices (CIEDs) by manual
      traction during orthotopic heart transplantation (OHT) sometimes results in
      retained lead fragments. Moreover, abandoned leads and retained lead fragments
      are a contraindication for magnetic resonance imaging (MRI) and may be a cause of
      CIED infection. OBJECTIVE: To eliminate complications of retained lead fragments,
      we completely removed residual leads using an excimer laser sheath technique
      during OHT. We report our clinical experience and high success rate of lead
      extraction using the excimer laser sheath compared with manual traction during
      OHT. METHODS AND RESULTS: We obtained data on 84 consecutive patients receiving
      OHT between August 2007 and August 2017. Thirty-nine of 84 patients had undergone
      CIED implantation before OHT and removal of all their leads was attempted during
      OHT. From 2007 to 2014, defibrillator and pacemaker leads were extracted by
      manual traction in all patients (N = 22). After 2015, all leads were extracted
      with the excimer laser sheath, and surgical assistance was prepared for the
      procedure (N = 17). Complete procedural success was achieved in 100% of patients
      in the excimer laser group and 77% of patients in the manual traction group.
      CONCLUSION: Extraction of abandoned leads using the excimer laser sheath system
      during OHT is novel and safe technique, and has a higher success rate than
      extraction using manual traction during OHT.

PMID- 30188914
TI  - Development of a broad spectrum glycoconjugate vaccine to prevent wound and
      disseminated infections with Klebsiella pneumoniae and Pseudomonas aeruginosa.
AB  - Klebsiella pneumoniae (KP) and Pseudomonas aeruginosa (PA) are important human
      pathogens that are associated with a range of infection types, including wound
      and disseminated infections. Treatment has been complicated by rising rates of
      antimicrobial resistance. Immunoprophylactic strategies are not constrained by
      antimicrobial resistance mechanisms. Vaccines against these organisms would be
      important public health tools, yet they are not available. KP surface O
      polysaccharides (OPS) are protective antigens in animal models of infection.
      Similarly, PA flagellin (Fla), the major subunit of the flagellar filament, is
      required for virulence and is a target of protective antibodies in animal models.
      We report herein the development of a combined KP and PA glycoconjugate vaccine
      comprised of the four most common KP OPS types associated with human infections
      (O1, O2, O3, O5), chemically linked to the two Fla types of PA (FlaA, FlaB).
      Conjugation of KP OPS to PA Fla enhanced anti-polysaccharide immune responses and
      produced a formulation that generated antibody titers to the four KP OPS types
      and both PA Fla antigens in rabbits. Passive transfer of vaccine-induced rabbit
      antisera reduced the bacterial burden and protected mice against fatal
      intravenous KP infection. Mice passively transferred with conjugate-induced
      antisera were also protected against PA infection after thermal injury with a
      FlaB-expressing isolate, but not a FlaA isolate. Taken together, these promising
      preclinical results provide important proof-of-concept for a broad spectrum human
      vaccine to prevent KP and PA infections.

PMID- 30188918
TI  - Effects of pharmacist intervention in Vancomycin treatment for patients with
      bacteremia due to Methicillin-resistant Staphylococcus aureus.
AB  - OBJECTIVE: We conducted a retrospective study based on composite endpoints for
      treatment failure to evaluate the effect of pharmacist-led VCM initial dose
      planning for Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia
      patients. METHODS: A retrospective cohort study was performed between pharmacist
      intervention and non-intervention groups. In this study, four types of failure
      were defined as the composite endpoint. When any one of the following failures
      occurred: 1) Death within 30 days from the start of VCM therapy, 2) Positive
      blood culture 7 days after the start of VCM therapy, 3) Change of VCM to another
      anti-MRSA agent, and 4) Development of nephrotoxicity, we considered that VCM
      treatment had failed. Survival time analysis was conducted with the Kaplan-Meier
      method and Cox's proportional hazard model that included seven predefined
      parameters: pharmacist intervention, age, sex, weight, baseline VCM trough
      concentration, Charlson Comorbidity Index (CCI), and Pitt Bacteremia score (PBS).
      The effect of pharmacist intervention was studied as the survival probability
      estimated from the period of time from the start of VCM administration to the
      earliest failure. RESULTS: The survival rate at 30 days after starting VCM
      therapy, at the end of follow-up, was 53.1 and 82.1% in the non-intervention and
      intervention groups, respectively. A significant survival time prolongation was
      noted in the intervention group (p = 0.011, log rank test). Among the seven
      parameters, only pharmacist intervention was significantly different and its
      hazard ratio was 0.26 (p = 0.014). The survival probability of the intervention
      group was higher than that of the non-intervention group for the time to each
      failure. In subgroup analyses, a significant difference was noted in male
      patients between the intervention and non-intervention groups (p = 0.005). Age
      was categorized into those under and over 65 years old. For those over 65 years
      old, a significant difference was shown between the groups (p = 0.018).
      CONCLUSION: To our knowledge, this is the first study to evaluate the failure of
      VCM treatment based on the composite endpoint. Pharmacist intervention through
      the initial VCM dose planning could maintain a balance between the efficacy and
      safety of VCM treatment and might avoid treatment failure for patients with MRSA
      bacteremia. Further investigations with large sample sizes are required to
      confirm our findings.

PMID- 30188916
TI  - Colorectal cancer molecular classification using BRAF, KRAS, microsatellite
      instability and CIMP status: Prognostic implications and response to
      chemotherapy.
AB  - OBJECTIVE: The aim of this study was to validate a molecular classification of
      colorectal cancer (CRC) based on microsatellite instability (MSI), CpG island
      methylator phenotype (CIMP) status, BRAF, and KRAS and investigate each subtype's
      response to chemotherapy. DESIGN: This retrospective observational study included
      a population-based cohort of 878 CRC patients. We classified tumours into five
      different subtypes based on BRAF and KRAS mutation, CIMP status, and MSI.
      Patients with advanced stage II (T4N0M0) and stage III tumours received 5
      fluoruracil (5-FU)-based chemotherapy or no adjuvant treatment based on clinical
      criteria. The main outcome was disease-free survival (DFS). RESULTS: Patients
      with the combination of microsatellite stable (MSS) tumours, BRAF mutation and
      CIMP positive exhibited the worst prognosis in univariate (log rank P<0.0001) and
      multivariate analyses (hazard ratio 1.75, 95% CI 1.05-2.93, P = 0.03) after
      adjusting for age, sex, chemotherapy, and TNM stage. Treatment with 5-FU-based
      regimens improved prognosis in patients with the combination of MSS tumours, KRAS
      mutation and CIMP negative (log rank P = 0.003) as well as in patients with MSS
      tumours plus BRAF and KRAS wild-type and CIMP negative (log-rank P<0.001). After
      adjusting for age, sex, and TNM stage in the multivariate analysis, only patients
      with the latter molecular combination had independently improved prognosis after
      adjuvant chemotherapy (hazard ratio 2.06, 95% CI 1.24-3.44, P = 0.005).
      CONCLUSION: We confirmed the prognostic value of stratifying CRC according to
      molecular subtypes using MSI, CIMP status, and somatic KRAS and BRAF mutation.
      Patients with traditional chromosomally unstable tumours obtained the best
      benefit from adjuvant 5-FU-based chemotherapy.

PMID- 30188919
TI  - How survival curves affect populations' vulnerability to climate change.
AB  - Human activities are exposing organisms not only to direct threats (e.g. habitat
      loss) but also to indirect environmental pressures such as climate change, which
      involves not just directional global warming but also increasing climatic
      variability. Such changes will impact whole communities of organisms and the
      possible effects on population dynamics have raised concerns about increased
      extinction rates. Conservation-minded approaches to extinction risk vary from
      range shifts predicted by climate envelope models with no population dynamics to
      population viability analyses that ignore environmental variability altogether.
      Our modelling study shows that these extremes are modelling responses to a
      spectrum of environmental sensitivity that organisms may exhibit. We show how the
      survival curve plays a major role in how environmental variability leads to
      population fluctuations. While it is often supposed that low-fecundity organisms
      (those with high parental investment) will be the most vulnerable to climate
      change, it is those with high fecundity (low parental investment) that are likely
      to be more sensitive to such changes. We also find that abundance variations in
      high fecundity populations is driven primarily by fluctuations in the survival of
      early life stages, the more so if those environmental changes are autocorrelated
      in time. We show which types of conservation actions are most appropriate for a
      number of real populations. While the most effective conservation actions for
      organisms of low fecundity is to avoid killing them, for populations with high
      fecundity (and low parental investment), our study suggests conservation should
      focus more on protecting early life stages from hostile environments.

PMID- 30188920
TI  - SMAD1/5 signaling in osteoclasts regulates bone formation via coupling factors.
AB  - Bone remodeling occurs via coupling between bone resorption by osteoclasts and
      bone formation by osteoblasts. The mechanisms that regulate osteoclast signals to
      osteoblasts are not well understood. Published studies have reported that BMP
      signaling in osteoclasts regulate osteoclast coupling targets. To investigate the
      necessity of canonical BMP signaling on osteoclast differentiation and coupling,
      we mated Smad1fl/fl; Smad5fl/fl mice to c-Fms-Cre mice. We analyzed male mice at
      3 months of age to determine the skeletal phenotype of the Smad1fl/fl;
      Smad5fl/fl;c-Fms-Cre (SMAD1/5 cKO) mice. There was a 1.2-fold decrease in
      trabecular BV/TV in SMAD1/5 cKO. Analyses of osteoclast serum markers in SMAD1/5
      cKO mice, showed a significant increase in CTX-1 (1.5 fold) and TRAP ELISA (3
      fold) compared to control mice. In these same mice, there was a 1.3-fold increase
      in cortical thickness. Consistent with the increase in cortical thickness, we
      found a 3-fold increase in osteoblast activity as measured by P1NIP ELISA assay
      from SMAD1/5 cKO mice. To explain the changes in cortical thickness and P1NP
      activity, we determined conditioned media from SMAD1/5 cKO osteoclast cultures
      enhanced mineralization of an osteoblast cell line and coupling factors expressed
      by osteoclasts that regulate osteoblast activity Wnt1 (4.5-fold increase), Gja1
      (3-fold increase) and Sphk1 (1.5-fold increase) were all upregulated in
      osteoclasts from SMAD1/5 cKO compared to control osteoclasts. Lastly osteoclasts
      treated with dorsomorphin, a chemical inhibitor of SMAD1/5 signaling,
      demonstrates an increase in Wnt1 and Gja1 expression similar to the SMAD1/5 cKO
      mice. Previous studies demonstrated that TGF-beta signaling in osteoclasts leads
      to increases in WNT1 expression by osteoclasts. Therefore, our data suggest that
      TGF-beta and BMP signaling pathways in osteoclasts could act in an antagonistic
      fashion to regulate osteoblast activity through WNT1 and other coupling factors.

PMID- 30188922
TI  - Effect of personality traits on driving style: Psychometric adaption of the
      multidimensional driving style inventory in a Chinese sample.
AB  - Driving style is an important factor in driving psychology, which is useful for
      effectively evaluating driving behaviors. Exploring driving style in a Chinese
      sample could help understand the overall situation of Chinese drivers. This study
      aims to develop a measurement of driving style fit for the Chinese situation and
      to validate the validity and reliability of this scale. In this study, 296
      drivers from China completed the Chinese version of the multidimensional driving
      style inventory (MDSI), the Big Five Inventory (BFI), and the Driver Behavior
      Questionnaire (DBQ) as well as several questions about socio-demographic
      information. After testing the assumed structure by a confirmatory factor
      analysis, and adjusting the structure, a brief version of Chinese version of MDSI
      with twelve items categorized into four driving styles, namely, risky style,
      angry- high-velocity style, careful style and anxious style was revised. The
      validity and reliability of the scales were acceptable. The results showed that
      driving styles were closely correlated with self-reported driving behaviors.
      Specifically, risky style, angry- high-velocity style, and anxious style are all
      positively associated with dangerous driving behaviors. Meanwhile, careful style
      was positively associated with positive driving behaviors and negatively
      correlated with dangerous driving behaviors. Anxious was also found to be
      negatively associated with fines. For personality, we found a positive
      relationship between risky, angry- high-velocity, careful and anxious styles and
      the personality traits that often have negative effects on driving, such as
      extraversion and neuroticism. Meanwhile, these three styles were negatively
      correlated with conscientiousness and agreeableness in general. In addition,
      careful style was positively correlated with conscientiousness and agreeableness.
      The current study shows convincing evidence for the validity and reliability of
      the brief MDSI-C and develops a useful tool for identify the driving style of
      Chinese drivers for future research and relevant departments of road safety.

PMID- 30188923
TI  - Changing interactions among persistent species as the major driver of seasonal
      turnover in plant-caterpillar interactions.
AB  - beta diversity of herbivorous insects in the tropics is usually very high, and
      there is often strong dissimilarity in herbivore species composition across
      different spatial scales and different abiotic gradients. Similarly, turnover is
      high for trophic interactions between herbivorous insects and their host plants.
      Two factors have been proposed to explain temporal or spatial differences in
      trophic interactions: changes in species composition and temporal changes in the
      behavior of shared species. The goal of this study was to evaluate determinants
      of high beta diversity of trophic interactions between lepidopteran caterpillars
      and their host plants across dry and rainy seasons and their transitions. Over
      the course of a year, interaction diversity data were collected from 275
      temporary plots in Cerrado vegetation, comprising 257 species of caterpillars,
      137 species of host plants and 503 different trophic interactions. All these
      diversity parameters varied across seasons. Species assemblages of caterpillars
      and plants were different among the four seasons, and there was a high turnover
      of interactions between the seasons. The high temporal beta diversity of trophic
      interactions was mostly due to interaction rewiring between co-occurring species,
      as opposed to changes in species composition over time.

PMID- 30188921
TI  - Cross-tissue eQTL enrichment of associations in schizophrenia.
AB  - The genome-wide association study of the Psychiatric Genomics Consortium
      identified over one hundred schizophrenia susceptibility loci. The number of non
      coding variants discovered suggests that gene regulation could mediate the effect
      of these variants on disease. Expression quantitative trait loci (eQTLs)
      contribute to variation in levels of mRNA. Given the co-occurrence of
      schizophrenia and several traits not involving the central nervous system (CNS),
      we investigated the enrichment of schizophrenia associations among eQTLs for four
      non-CNS tissues: adipose tissue, epidermal tissue, lymphoblastoid cells and
      blood. Significant enrichment was seen in eQTLs of all tissues: adipose (beta =
      0.18, p = 8.8 * 10-06), epidermal (beta = 0.12, p = 3.1 * 10-04), lymphoblastoid
      (beta = 0.19, p = 6.2 * 10-08) and blood (beta = 0.19, p = 6.4 * 10-06). For
      comparison, we looked for enrichment of association with traits of known
      relevance to one or more of these tissues (body mass index, height, rheumatoid
      arthritis, systolic blood pressure and type-II diabetes) and found that
      schizophrenia enrichment was of similar scale to that observed when studying
      diseases in the context of a more likely causal tissue. To further investigate
      tissue specificity, we looked for differential enrichment of eQTLs with relevant
      Roadmap affiliation (enhancers and promoters) and varying distance from the
      transcription start site. Neither factor significantly contributed to the
      enrichment, suggesting that this is equally distributed in tissue-specific and
      cross-tissue regulatory elements. Our analyses suggest that functional correlates
      of schizophrenia risk are prevalent in non-CNS tissues. This could be because of
      pleiotropy or the effectiveness of variants affecting expression in different
      contexts. This suggests the utility of large, single-tissue eQTL experiments to
      increase eQTL discovery power in the study of schizophrenia, in addition to
      smaller, multiple-tissue approaches. Our results conform to the notion that
      schizophrenia is a systemic disorder involving many tissues.

PMID- 30188925
TI  - Developing SENSES: Student experience of non-shared environment scales.
AB  - Twin and adoption studies find that non-shared environmental (NSE) factors
      account for variance in most behavioural traits and offer an explanation for why
      genetically identical individuals differ. Using data from a qualitative
      hypothesis-generating study we designed a quantitative measure of pupils' non
      shared experiences at the end of formal compulsory education (SENSES: Student
      Experiences of Non-Shared Environment Scales). In Study 1 SENSES was administered
      to n = 117 16-19 year old twin pairs. Exploratory Factor Analysis yielded a 49
      item 10 factor solution which explained 63% of the variance in responses. SENSES
      showed good internal consistency and convergent and divergent validity. In Study
      2 this factor structure was confirmed with data from n = 926 twin pairs and
      external validity was demonstrated via significant correlations between 9 SENSES
      factors and both public examination performance and life satisfaction. These
      studies lend preliminary support to SENSES but further research is required to
      confirm its psychometric properties; to assess whether individual differences in
      SENSES are explained by NSE effects; and to explore whether SENSES explains
      variance in achievement and wellbeing.

PMID- 30188924
TI  - 1H-NMR and MALDI-TOF MS as metabolomic quality control tests to classify platelet
      derived medium additives for GMP compliant cell expansion procedures.
AB  - INTRODUCTION: Ex vivo cell expansion under Good Manufacturing Practice (GMP)
      guidelines can be performed using medium additives containing human growth
      factors from platelets. These products can differently affect proliferation of
      adipose mesenchymal stromal stem cells (ASC). Qualification of medium additive
      performance is required for validation under GMP regulations: assessment of
      growth factor concentrations is not sufficient to predict the biological activity
      of the product batch. Proton nuclear magnetic resonance spectrometry (1H-NMR) and
      matrix-assisted laser desorption/ionization time of flight mass spectroscopy
      (MALDI-TOF MS) provide wide molecular characterization of samples. AIMS: We aimed
      to assess if 1H-NMR and MALDI-TOF MS techniques can be used as quality control
      test potentially predicting the impact of a medium additive on cell
      proliferation. METHODS: We tested the impact on ASC growth rate (cell
      proliferation assessment and cell morphology analysis) of four medium additives,
      obtained by different methods from human platelet apheresis product. In order to
      classify each medium additive, we evaluated growth factor concentrations and
      spectra obtained by 1H-NMR and by MALDI-TOF MS. RESULTS: Medium additive obtained
      by CaCl2 activation of platelet rich products induced higher proliferation rate
      vs additive derived from platelet depleted ones. Additives obtained by freeze-and
      thaw methods weakly induced ASC proliferation. As expected, principal component
      analysis of growth factor concentrations did not unravel specific biochemical
      features characterizing medium additives in relation with their biological
      activity. Otherwise, while 1H-NMR showed a partial resolution capacity, analysis
      of MALDI-TOF MS spectra allowed unambiguous distinction between the medium
      additives we used to differently stimulate cell growth in vitro. DISCUSSION:
      MALDI-TOF and, despite limitations, 1H-NMR are promising cost effective and
      reliable quality controls to classify the potential of a medium additive to
      promote ASC growth. This can represent, after further investigations and
      appropriate validation, a significant advantage for GMP compliant manufacturing
      of advanced cell therapy products.

PMID- 30188926
TI  - Relationships between histogram analysis of ADC values and complex 18F-FDG-PET
      parameters in head and neck squamous cell carcinoma.
AB  - PURPOSE: Histogram analysis is an emergent imaging technique to further analyze
      radiological images and to obtain imaging biomarker. In head and neck cancer, MRI
      and PET are routinely used in clinical practice. The aim of this study was to
      analyze associations between histogram based ADC parameters and complex FDG-PET
      derived parameters in head and neck squamous cell carcinoma (HNSCC). METHODS: 34
      patients (26% female, mean age, 56.7 +/- 10.2 years) with primary HNSCC were
      prospectively included into the study. ADC histogram parameters were calculated
      by inhouse made matlab software using a whole lesion measurement. For each tumor,
      maximum and mean standardized uptake values (SUVmax, SUVmean), Total Lesion
      Glycolysis (TLG) and Metabolic Tumor Volume (MTV) were determined on PET-images.
      Spearman's correlation coefficient (rho) was used to analyze associations between
      investigated parameters. Benjamini-Hochberg correction was used to adjust for
      multiple testing. Mann-Whitney test was used for group discrimination. P-values <
      0.05 were taken to indicate statistical significance. RESULTS: The correlation
      analysis in the whole tumor group revealed a statistically significant
      correlation between entropy and MTV as well as TLG (rho = 0.67, P<0.0001 and rho
      = 0.61, P = 0.0002 respectively). There were statistically significant
      differences between T1/2 and T3/4 tumors in the following parameters: entropy
      (2.07 +/- 0.36 vs 2.61 +/- 0.43, P = 0.007), SUVmax (10.79 +/- 4.13 vs 17.93 +/-
      5.89, P = 0.007), SUVmean (6.39 +/- 2.48 vs 9.81 +/- 4.49, P = 0.01), SUVmin
      (4.09 +/- 1.57 vs 6.34 +/- 2.59, P = 0.03), MTV (9.50 +/- 7.92 vs 20.36 +/-
      13.30, P = 0.02), TGU (55.97 +/- 39.09 vs 212.3 +/- 186.3, P = 0.002).
      CONCLUSION: This study showed that entropy derived from ADC maps is strongly
      associated with MTV and TLG in HNSCC. Entropy, SUVmax, SUVmean, TLG and MTV were
      statistically significant higher in T3/4 tumors in comparison to T1/2 carcinomas.

PMID- 30188927
TI  - Dorsal penile nerve block versus eutectic mixture of local anesthetics cream for
      pain relief in infants during circumcision: A meta-analysis.
AB  - OBJECTIVE: To compare dorsal penile nerve block (DPNB) and eutectic mixture of
      local anesthetics (EMLA) cream for pain relief in infants during circumcision.
      METHODS: We systematically searched Medline via PubMed, Embase, CNKI and the
      Cochrane Library Center Register to identify randomized controlled trials up to
      March 2018. Effect estimates were performed in random effect models. Mean neonate
      infant pain scale (NIPS) scores, incidence of hematoma, edema and erythema, mean
      heart rate were conducted to assessed the effect of analgesia. We found that the
      EMLA had significantly higher pain scores compared to DPNB (SMD = 3.72, 95% CI
      1.27-6.17, P = 0.003). In DPNB group, the incidence of hematoma was significantly
      higher than EMLA group, OR = 0.03, 95% CI 0.00-0.24, P = 0.001. The analysis did
      not show any significant differences in mean heart rate and the risk of edema and
      erythema between EMLA and DPNB group (SMD = 21.71, 95% CI = -0.88-44.30, P = 0.06
      & OR = 0.40, 95% CI 0.15-1.07, P = 0.07 & OR = 7.33, 95% CI 0.84-64.07, P =
      0.07). CONCLUSION: Based on the pooled results from the included studies, we
      found that DPNB was significantly more effective in pain relief as indicated by
      mean NIPS score than EMLA in infants during circumcision. However, use of DPNB
      significantly increased the risk of hematoma.

PMID- 30188928
TI  - Validity and reliability of the Mandarin version of Patient Dignity Inventory
      (PDI-MV) in cancer patients.
AB  - Nurses play an important role in maintaining patients' dignity. How to measure
      patients' dignity and dignity-related distress is an important issue in nursing
      care. Use of a reliable and valid tool assessing dignity-related distress in
      patients is necessary. The study investigated the validity and reliability of the
      Mandarin Version of the Patient Dignity Inventory (PDI-MV) in cancer patients.
      The Patient Dignity Inventory (PDI) was translated into the Mandarin language
      using forward and back translation. A convenience sample of 125 adult cancer
      patients was recruited from the oncology ward of a medical center in southern
      Taiwan. Factor analysis with principal axis factoring extraction method and
      oblique rotation (promax) was used to assess the construct validity. Concurrent
      validity was established using the Patient Health Questionnaire-9 (PHQ-9),
      Mandarin version of Demoralization Scale (DS-MV) and the Rosenberg Self-Esteem
      Scale (RSES). Internal consistency was used to examine the reliability. Data were
      collected from February to May 2016. As a result of the factor analysis, four
      factors, including existential distress, loss of support and sense of meaning,
      symptom distress, and loss of autonomy. Concurrent validity showed that the PDI
      MV was significantly correlated with the PHQ-9 (r = 0.25-0.54), DS-MV (r = 0.30
      0.58) and the RSES (r = - 0.08 to-0.30), Cronbach's alpha coefficients for the
      PDI-MV and four factors were 0.95, 0.95, 0.84, 0.83, and 0.89 respectively. The
      PDI-MV is a psychometrically sound instrument assessing a broad range of dignity
      related distress issues in cancer patients.

PMID- 30188929
TI  - Metabolic syndrome in Xinjiang Kazakhs and construction of a risk prediction
      model for cardiovascular disease risk.
AB  - BACKGROUND: The high prevalence of metabolic syndrome (MetS) and cardiovascular
      diseases (CVD) is observed among Kazakhs in Xinjiang. Because MetS may
      significantly predict the occurrence of CVD, the inclusion of CVD-related
      indicators in metabolic network may improve the predictive ability for a CVD-risk
      model for Kazakhs in Xinjiang. METHODS: The study included 2,644 subjects who
      were followed for 5 years or longer. CVD cases were identified via medical
      records of the local hospitals from April 2016 to August 2017. Factor analysis
      was performed in 706 subjects (267 men and 439 women) with MetS to extract CVD
      related potential factors from 18 biomarkers tested in a routine health check-up,
      served as a synthetic predictor (SP). We evaluated the predictive ability of the
      CVD-risk model using age and SP, logistic regression discrimination for internal
      validation (n = 384; men = 164, women = 220) and external validation (n = 219;
      men = 89, women = 130), calculated the probability of CVD for each participant,
      and receiver operating characteristic curves. RESULTS: According to the
      diagnostic criteria of JIS, the prevalence of MetS in Kazakh was 30.9%. Seven
      potential factors with a similar pattern were obtained from men and women and
      comprised the CVD predictors. When predicting CVD in the internal validation, the
      area under the curve (AUC) were 0.857 (95%CI 0.807-0.898) for men and 0.852
      (95%CI 0.809-0.889) for women, respectively. In the external validation, the AUC
      to predict CVD were 0.914 (95%CI 0.832-0.963) for men and 0.848 (95%CI 0.774
      0.905) for women. It is suggested that SP might serve as a useful tool in
      identifying CVD with in Kazakhs, especially for Kazakhs men. CONCLUSIONS: Among 7
      potential factors were extracted from 18 biomarkrs in Kazakhs with MetS, and SP
      may be used for CVD risk assessment.

PMID- 30188930
TI  - Features of patients with rheumatoid arthritis whose debut joint is a foot or
      ankle joint: A 5,479-case study from the IORRA cohort.
AB  - BACKGROUND: Foot and ankle joint disorders are serious issues for patients with
      rheumatoid arthritis (RA). We compared the differences between patients with RA
      whose first symptom involved a foot or ankle joint (FOOT group) versus other
      joints (non-FOOT group) within the Institute of Rheumatology, Rheumatoid
      Arthritis (IORRA) cohort in our institute. PATIENTS AND METHODS: In the IORRA
      survey conducted in April 2016, patients were invited to complete six
      questionnaires about their first symptom at RA onset, current foot or ankle
      symptoms, daily living activities, and mental health. Disease activity, clinical
      laboratory variables, functional disability, quality of life, use and ratio of
      anti-inflammatory and antirheumatic drugs, daily living activities and mental
      health were compared between the two groups. RESULTS: Among 5,637 Japanese
      patients with RA who participated in the IORRA survey on April 2016, 5,479
      (97.2%) responded to the questionnaire regarding their debut joint. Of these
      patients, 2,402 (43.8%) reported that their first symptom of RA involved a foot
      or ankle joint. The FOOT group (n = 2,164) had higher disease activity, higher
      disabilities, lower quality of life, lower activities of daily living, and poorer
      mental health and used anti-inflammatory drugs at a higher rate and at higher
      doses compared with the non-FOOT group (n = 2,164). On the other hand, the use of
      medications to suppress the disease activity of RA was similar between the
      groups. CONCLUSION: Clinicians should pay more attention to foot and ankle joints
      in daily practice so as not to underestimate the disease activity of RA.

PMID- 30188932
TI  - The Trusted Server: A secure computational environment for privacy compliant
      evaluations on plain personal data.
AB  - A growing framework of legal and ethical requirements limit scientific and
      commercial evaluation of personal data. Typically, pseudonymization, encryption,
      or methods of distributed computing try to protect individual privacy. However,
      computational infrastructures still depend on human system administrators. This
      introduces severe security risks and has strong impact on privacy: system
      administrators have unlimited access to the computers that they manage including
      encryption keys and pseudonymization-tables. Distributed computing and data
      obfuscation technologies reduce but do not eliminate the risk of privacy leakage
      by administrators. They produce higher implementation effort and possible data
      quality degradation. This paper proposes the Trusted Server as an alternative
      approach that provides a sealed and inaccessible computational environment in a
      cryptographically strict sense. During operation or by direct physical access to
      storage media, data stored and processed inside the Trusted Server can by no
      means be read, manipulated or leaked, other than by brute-force. Thus, secure and
      privacy-compliant data processing or evaluation of plain person-related data
      becomes possible even from multiple sources, which want their data kept mutually
      secret.

PMID- 30188931
TI  - Evaluation of potential effects of Plastin 3 overexpression and low-dose SMN
      antisense oligonucleotides on putative biomarkers in spinal muscular atrophy
      mice.
AB  - OBJECTIVES: Spinal muscular atrophy (SMA) is a devastating motor neuron disorder
      caused by homozygous loss of the survival motor neuron 1 (SMN1) gene and
      insufficient functional SMN protein produced by the SMN2 copy gene. Additional
      genetic protective modifiers such as Plastin 3 (PLS3) can counteract SMA
      pathology despite insufficient SMN protein. Recently, Spinraza, an SMN antisense
      oligonucleotide (ASO) that restores full-length SMN2 transcripts, has been FDA-
      and EMA-approved for SMA therapy. Hence, the availability of biomarkers allowing
      a reliable monitoring of disease and therapy progression would be of great
      importance. Our objectives were (i) to analyse the feasibility of SMN and of six
      SMA biomarkers identified by the BforSMA study in the Taiwanese SMA mouse model,
      (ii) to analyse the effect of PLS3 overexpression on these biomarkers, and (iii)
      to assess the impact of low-dose SMN-ASO therapy on the level of SMN and the six
      biomarkers. METHODS: At P10 and P21, the level of SMN and six putative biomarkers
      were compared among SMA, heterozygous and wild type mice, with or without PLS3
      overexpression, and with or without presymptomatic low-dose SMN-ASO subcutaneous
      injection. SMN levels were measured in whole blood by ECL immunoassay and of six
      SMA putative biomarkers, namely Cartilage Oligomeric Matrix Protein (COMP),
      Dipeptidyl Peptidase 4 (DPP4), Tetranectin (C-type Lectin Family 3 Member B,
      CLEC3B), Osteopontin (Secreted Phosphoprotein 1, SPP1), Vitronectin (VTN) and
      Fetuin A (Alpha 2-HS Glycoprotein, AHSG) in plasma. RESULTS: SMN levels were
      significantly discernible between SMA, heterozygous and wild type mice. However,
      no significant differences were measured upon low-dose SMN-ASO treatment compared
      to untreated animals. Of the six biomarkers, only COMP and DPP4 showed high and
      SPP1 moderate correlation with the SMA phenotype. PLS3 overexpression neither
      influenced the SMN level nor the six biomarkers, supporting the hypothesis that
      PLS3 acts as an independent protective modifier.

PMID- 30188933
TI  - Testing for physical validity in molecular simulations.
AB  - Advances in recent years have made molecular dynamics (MD) and Monte Carlo (MC)
      simulations powerful tools in molecular-level research, allowing the prediction
      of experimental observables in the study of systems such as proteins, membranes,
      and polymeric materials. However, the quality of any prediction based on
      molecular dynamics results will strongly depend on the validity of underlying
      physical assumptions. Unphysical behavior of simulations can have significant
      influence on the results and reproducibility of these simulations, such as
      folding of proteins and DNA or properties of lipid bilayers determined by cutoff
      treatment, dynamics of peptides and polymers affected by the choice of
      thermostat, or liquid properties depending on the simulation time step. Motivated
      by such examples, we propose a two-fold approach to increase the robustness of
      molecular simulations. The first part of this approach involves tests which can
      be performed by the users of MD programs on their respective systems and setups.
      We present a number of tests of different complexity, ranging from simple post
      processing analysis to more involved tests requiring additional simulations.
      These tests are shown to significantly increase the reliability of MD simulations
      by catching a number of common simulation errors violating physical assumptions,
      such as non-conservative integrators, deviations from the Boltzmann ensemble, and
      lack of ergodicity between degrees of freedom. To make the usage as easy as
      possible, we have developed an open-source and platform-independent Python
      library (https://physical-validation.readthedocs.io) implementing these tests.
      The second part of the approach involves testing for code correctness. While
      unphysical behavior can be due to poor or incompatible choices of parameters by
      the user, it can just as well originate in coding errors within the program. We
      therefore propose to include physical validation tests in the code-checking
      mechanism of MD software packages. We have implemented such a validation for the
      GROMACS software package, ensuring that every major release passes a number of
      physical sanity checks performed on selected representative systems before
      shipping. It is, to our knowledge, the first major molecular mechanics software
      package to run such validation routinely. The tests are, as the rest of the
      package, open source software, and can be adapted for other software packages.

PMID- 30188934
TI  - Effects of picosecond laser on the multi-colored tattoo removal using Hartley
      guinea pig: A preliminary study.
AB  - Picosecond lasers have emerged as the leading technology for tattoo removal due
      to their shorter pulse lengths. To clarify the features of picosecond lasers, we
      compared picosecond and nanosecond lasers in their ability to remove multi
      colored tattoo in an animal model. We first compared a nanosecond quality
      switched Nd:YAG laser with picosecond Alexandrite and quality-switched Nd:YAG
      lasers and then the picosecond quality-switched Nd:YAG laser with the picosecond
      Alexandrite laser, using a guinea pig model. The colors in the tattoos included
      red, orange, yellow, green, blue, and black. Guinea pigs were treated for one
      session with each type of laser. The clearance of pigmentation and local
      reactions were evaluated based on clinical photographic assessment, quantitative
      assessment using a colorimeter, histopathology, and electron microscopic
      examination before laser treatment, immediately after, and at 3 weeks after the
      treatment. Regardless of pulse duration, a 532-nm laser was the most effective in
      clearing red, orange, and yellow pigments, although the overall effect and safety
      was better with the picosecond 532 nm laser. A picosecond 755 nm laser
      demonstrated excellent efficacy in removing only green and blue pigments. a
      picosecond 1064 nm laser demonstrated some effects on non-black colored tattoos.
      In terms of safety, picosecond lasers produced less tissue injury than nanosecond
      lasers. Conclusively, picosecond lasers are more effective and safer than
      nanosecond lasers.

PMID- 30188935
TI  - Associations and interactions between variants in selenoprotein genes,
      selenoprotein levels and the development of abdominal aortic aneurysm, peripheral
      arterial disease, and heart failure.
AB  - BACKGROUND: Little is known on the role of selenoprotein genes in cardiovascular
      disease. This study examines the associations of the SEPP1, SELENOS, TXNRD1,
      TXNRD2, GPX4, and SOD2 polymorphisms and selenoprotein P (SeP) and thioredoxin
      concentrations with the development of abdominal aortic aneurysm (AAA) and
      aortoiliac occlusive disease (AOID), as well as their influence on cardiac
      phenotype. METHODS: 564 patients with AAA, 400 patients with AIOD, and 543
      controls were enrolled and characterized for coronary artery disease, myocardial
      infarction, and systolic heart failure (HF) occurrence. In AAA, the coexistence
      of peripheral arterial disease (PAD) was examined. Genotypes were determined
      using TaqMan-based assays. Selenoprotein concentration was assessed using the
      ELISA method. RESULTS: The SELENOS rs34713741T, SEPP1 rs3877899A, and GPX4
      rs713041T alleles were related to a 30-60% increase in the AIOD/PAD risk in the
      recessive or dominant model (all associations at P < .05). The SEPP1 rs3877899A
      allele was a protective factor for the development of AAA without concomitant PAD
      (OR = 0.68 for the dominant model, P = .014), but not AAA with concomitant PAD.
      The cumulative two-locus effects of selenoprotein genes on the AAA/AIOD risk were
      observed, including the multiplicative interaction between the SELENOS
      rs34713741T and GPX4 rs713041T alleles (both in the recessive model) affecting
      the AIOD risk (OR = 5.27, P = .001) and its clinical phenotype. Coexistence of HF
      in aortic diseases was related to both the SEPP1 rs7579A allele (OR = 1.83 for
      carriers, P = .013) and increased SeP concentrations; SeP level >=8.5 mg/mL
      caused a 3.5-fold increase in the risk of HF. In AAA, SeP levels were correlated
      with BMI (r = -0.575, P < .0001). CONCLUSIONS: Our results provide evidence that
      selenoprotein polymorphisms constitute a risk factor for HF and peripheral
      atherosclerosis, but prevent the development of AAA. Excessive weight might
      result in reduced antioxidant reserve efficiency in AAA. Validation studies are
      required to establish whether SeP concentration may be a marker for HF.

PMID- 30188937
TI  - Habitat overlap between Asiatic black bear Ursus thibetanus and red panda Ailurus
      fulgens in Himalaya.
AB  - Studying habitat overlap between sympatric species is one of the best ways to
      identify interspecies relationships and to direct conservation efforts so that
      multiple species can benefit. However, studies exploring interspecies
      relationships are very limited in Nepal, making it difficult for the government
      of Nepal and conservation partners to manage wildlife in their habitats,
      especially in Himalayan protected areas. In this study, we identified habitat
      overlap between Asiatic black bear (Ursus thibetanus) and red panda (Ailurus
      fulgens) as well as important habitat types for both species in the Makalu Barun
      National Park, Nepal using Maximum Entropy (MaxEnt) modeling. GPS points of
      species occurrence were collected from the field, and environmental variables
      were extracted from freely available sources. We found that the study area
      contained 647 km2 of Asiatic black bear habitat and 443 km2 of the red panda
      habitat. 368 km2 supported both species, which constituted 57% of the Asiatic
      black bear habitat and 83% of the red panda habitat. We found that conifer forest
      was the most important habitat type for both species. Because the largest
      portions of both species' habitat were located inside the buffer zone, a
      peripheral zone of national park, conservation efforts for these sympatric
      species should be focused inside the buffer zone to be most effective.

PMID- 30188936
TI  - Evaluation of the recombinant antigens B2t and 2B2t, compared with hydatid fluid,
      in IgG-ELISA and immunostrips for the diagnosis and follow up of CE patients.
AB  - Cystic echinococcosis (CE) is one of the most widespread helminthic zoonoses and
      is caused by the tapeworm Echinococcus granulosus complex. CE diagnosis and
      monitoring primarily rely on imaging techniques, complemented by serology. This
      is usually approached by the detection of IgG antibodies against hydatid fluid
      (HF), but the use of this heterogeneous antigenic mixture results in a variable
      percentage of false positive and negative results, and has shown to be useless
      for follow-up due to the long persistence of anti-HF antibodies in cured
      patients. To improve test performances and standardization, a number of
      recombinant antigens mainly derived from HF have been described, among them the
      B2t and 2B2t antigens. The performance of these antigens in the diagnosis and
      follow up of patients with CE has been so far evaluated on a limited number of
      samples. Here, we evaluated the performances of tests based on B2t and 2B2t
      recombinant antigens compared to HF in IgG-ELISA and immunochromatography (IC)
      for the diagnosis and follow-up of patients with CE in a retrospective cohort
      study. A total of 721 serum samples were collected: 587 from 253 patients with CE
      diagnosed by ultrasonography (US), 42 from patients with alveolar echinococcosis
      and 92 from healthy donors from Salamanca (Spain). The highest overall
      sensitivity was obtained with HF in ELISA (85.5%), followed by IC containing HF
      and 2B2t-HF (83.0% and 78.2%, respectively). The lowest sensitivity was obtained
      with B2t and 2B2t in ELISA (51.8%). The highest specificity was obtained with IC
      containing 2B2t-HF (100%), and the lowest with HF-ELISA (78.0%). The lowest cross
      reactivity with sera from patients with alveolar echinococcosis was detected with
      the recombinant antigens in ELISA (9.5% - 16.7%) and the highest with the HF-IC
      (64.3%). The results of B2t and 2B2t-ELISA were influenced by cyst stage, as
      classified by US according to the WHO-Informal Working Group on Echinococcosis
      (WHO-IWGE), with low sensitivity for inactive (CE4 and CE5) cysts, and by the
      drug treatment, with higher sensitivity in patients after drug treatment compared
      with patients not subjected to drug treatment. The two recombinant antigens in
      ELISA provided promising results for monitoring patients in follow-up, although
      their use is limited to patients with positive serology against them at the
      beginning of the follow-up. Potential biological reasons behind the low
      sensitivity of the recombinant antigens and possible strategies to enhance the
      performance of CE serology are discussed.

PMID- 30188938
TI  - Deformable 96-well cell culture plate compatible with high-throughput screening
      platforms.
AB  - Adherent cells such as endothelial cells sense applied mechanical stretch to
      adapt to changes in their surrounding mechanical environment. Despite numerous
      studies, signaling pathways underlying the cellular mechanosensing and adaptation
      remain to be fully elucidated partly because of the lack of tools that allow for
      a comprehensive screening approach. Conventionally, multi-well cell culture
      plates of standard configurations are used for comprehensive analyses in cell
      biology study to identify key molecules in a high-throughput manner. Given that
      situation, here we design a 96-well cell culture plate made of elastic silicone
      and mechanically stretchable using a motorized device. Computational analysis
      suggested that highly uniform stretch can be applied to each of the wells other
      than the peripheral wells. Elastic image registration-based experimental
      evaluation on stretch distributions within individual wells revealed the presence
      of larger variations among wells compared to those in the computational analysis,
      but a stretch level of 10%-that has been employed in conventional studies on
      cellular response to stretch-was almost achieved with our setup. We exposed
      vascular smooth muscle cells to cyclic stretch using the device to demonstrate
      morphological repolarization of the cells, i.e. typical cellular response to
      cyclic stretch. Because the deformable multi-well plate validated here is
      compatible with other high-throughput screening-oriented technologies, we expect
      this novel system to be utilized for future comprehensive analyses of stretch
      related signaling pathways.

PMID- 30188939
TI  - Informal caregiving and personality: Results of a population-based longitudinal
      study in Germany.
AB  - BACKGROUND: The aim of this study was to identify whether informal caregiving
      time is associated with personality factors longitudinally. METHODS: Longitudinal
      data were gathered from the German Socio-Economic Panel (GSOEP), a large
      nationally representative, longitudinal study of German households beginning in
      1984. Focusing on the association between informal caregiving and personality
      factors, data were used from the years 2005, 2009 and 2013. The GSOEP Big Five
      Inventory was used to assess personality factors. Informal caregiving hours were
      used as explanatory variable. The explanatory variable informal caregiving hours
      was categorized into 0 hours (reference), 1 hours, 2 hours, 3 hours, 4 hours, and
      5 hours and more. Age, marital status, educational level, employment status,
      income, self-rated health and disability were included as potential confounders
      in regression analysis. RESULTS: Adjusting for potential confounders, fixed
      effects regressions showed that whether or not someone provides informal care is
      markedly associated with changes in neuroticism. Given that an individual
      provides informal care, the actual number of care hours did not matter in most
      cases. Informal caregiving was not associated with openness to experience,
      extraversion and agreeableness. As regards conscientiousness, only '5 hours and
      more' on a typical Sunday was associated with an increase in conscientiousness
      (beta = .32, p < .05). Informal caregiving on a typical weekday or Saturday was
      not associated with changes in conscientiousness. CONCLUSION: Our findings stress
      the longitudinal association between informal caregiving and neuroticism.

PMID- 30188940
TI  - A cross-sectional study of partograph utilization as a decision making tool for
      referral of abnormal labour in primary health care facilities of Bangladesh.
AB  - BACKGROUND: In Bangladesh, female paramedics known as Family Welfare Visitors
      (FWVs), conduct normal deliveries in first-level primary care facilities, or
      Union Health and Family Welfare Centres (UH&FWC). Utilization of partographs
      allow for early identification of abnormal labour and referral for advanced care
      to Emergency Obstetric Care (EmOC) facilities. A systematic assessment of the
      quality of partograph utilization in clinical-decision making will contribute to
      understanding the use of the tool by health workers. METHODS: In 2013, the USAID
      supported MaMoni HSS project, led in country by Save the Children, trained FWVs
      on the use of partographs in five UH&FWCs in Habiganj district. As part of the
      follow-up after training, intrapartum case record forms, accompanying
      partographs, and referral registers for all obstetric cases managed in these five
      facilities from July 2013 to June 2014 were reviewed. Partographs were reviewed
      to identify abnormal labour cases based on pre-defined indications. All referred
      cases were ascertained from the case records in the referral registers. Five
      health workers were interviewed to assess their knowledge, attitude and
      experience in partograph use and to explore the challenges for referral decision
      making associated with the tool. RESULTS: A total of 1,198 deliveries were
      managed at the study sites, of which 663 presented with cervical dilatation of 8
      cm or less. Partographs were initiated in 98% of these cases. Indication of
      abnormal labour was found in 71 partographs (11%) and among them, only 1 was
      referred to a higher-level facility. Foetal heart rate and cervical dilatation
      were appropriately recorded in 61% and 70% of the partographs, respectively.
      Interviews with health workers revealed poor interpretation of referral
      indications from the partographs. Limited accessibility to the nearest EmOC
      facility, inadequate time for referral, and non-compliance to referral by clients
      were identified by the interviewed health workers as the key barriers for
      referral decision making. CONCLUSIONS: Supporting the health workers at first
      level primary care facilities to better interpret and act on partograph data in a
      timely manner, and strengthening the referral systems are needed to ensure that
      women in labour receive the prompt quality care they and their babies require to
      survive.

PMID- 30188941
TI  - Infants prefer a trustworthy person: An early sign of social cognition in
      infants.
AB  - Recently, various studies have clarified that humans can immediately make social
      evaluations from facial appearance and that such judgment have an important role
      in several social contexts. However, the origins and early development of this
      skill have not been well investigated. To clarify the mechanisms for the
      acquisition of this skill, we examined whether 6- to 8-month-old infants show a
      preference for a more trustworthy-looking person. Results showed that infants
      preferred a trustworthy face to an untrustworthy one when both faces were high in
      dominance. This difference was not seen when both faces were low in dominance.
      Moreover, this preference disappeared when the faces were upside down. These
      findings suggest that the perception of trustworthiness based on facial
      appearance emerges in early development with little social experience. Further
      research is needed to verify whether infants also perceive other traits, such as
      competence.

PMID- 30188942
TI  - Linking systemic angiogenic markers to synovial vascularization in rheumatoid
      arthritis.
AB  - BACKGROUND: Neoangiogenesis is a crucial event to promote the development of the
      hyperplasic proliferative pathologic synovium in Rheumatoid arthritis (RA).
      Ultrasound (US) is sensitive for detection of power Doppler (PD) vascularization.
      OBJECTIVE: To explore the associations between a set of complementary circulating
      angiogenic markers and a comprehensive US assessment in patients with RA.
      PATIENTS AND METHODS: Serum levels of eight angiogenic markers were measured by
      quantitative ELISAs in a total of 125 patients with RA, who were all
      systematically assessed in parallel by PDUS, performed on 32 joints. RESULTS:
      Serum levels of soluble Vascular Cell Adhesion Molecule-1 (sVCAM-1) and Tie-2
      were more likely to be increased in patients with synovial hyperemia detected on
      at least one joint (Power Doppler grade >=1). sVCAM-1, Tie-2 and Angiostatin
      concentrations gradually increased together with the grade of the
      semiquantitative PDUS scale and concentrations of these three markers were
      markedly increased in patients with moderate to marked hyperemia (Power Doppler
      grade 2 and 3). Levels of sVCAM-1, Tie-2, and Angiostatin correlated with a
      global arthritis sum score, defined by the sum of the semiquantitative PDUS
      scores for all joints examined. Levels of Tie-2 and Placenta Growth Factor (PlGF)
      were associated with PDUS features indicating residual disease activity.
      CONCLUSION: Our results support the relevance of measuring serum levels of
      vascular markers to evaluate the intensity and extent of synovial
      vascularization. Angiogenic markers, and particularly Tie-2, could be a valuable
      surrogate of active synovitis and their place in relation to PDUS in clinical
      practice deserve further investigation.

PMID- 30188943
TI  - Alcohol use disorder tied to development of chronic kidney disease: A nationwide
      database analysis.
AB  - INTRODUCTION: Alcohol use disorder (AUD) is a spectrum of high risk behaviors
      including alcohol abuse and dependence. Chronic kidney disease (CKD) is
      progressive loss of renal function for more or equal to 3 months or presence of
      any irreversible kidney damage. Common risk factors of CKD have been identified,
      but the impact of alcohol consumption on kidney function is controversial. The
      study aims to investigate the relationship between alcohol use disorder and CKD
      on a national scale. METHODS: This retrospective cohort study was conducted using
      Taiwan's National Health Insurance research database. Patients aged 20 years or
      older, without CKD and with the diagnosis of AUD (ICD-9-CM codes 303.X; 305.0,
      V113) from years 2000 to 2013 were enrolled. Control cohort was selected to match
      the demographics of the target population. Patients were followed until the end
      of 2013 or earlier if they developed CKD, died, or lost follow up. Baseline
      characteristics and comorbidities were identified for risk stratification.
      RESULTS: We identified 11639 patients in the AUD cohort and 46556 patients in the
      control cohort. Compared to patients in the control cohort, those in the AUD
      group were more likely to have multiple comorbidities (p < 0.001 for all
      comorbidities). After adjustment of age, gender, baseline comorbidities, and
      nonsteroidal anti-inflammatory drug use, the diagnosis of AUD was associated with
      an increased risk of CKD development (aHR = 1.62, 95% CI, 1.46-1.81). During the
      mean follow up periods of 6.47 (standard deviation (SD) = 3.80) years for the AUD
      cohort and 7.23 (SD = 3.75) years for the control cohort, the overall incidence
      density of CKD was significantly higher in patients with AUD than those in the
      control cohort (3.48 vs 6.51 per 1000 person-years, aHR = 1.68, 95% CI, 1.50
      1.87). Kaplan-Meier analysis showed that the AUD cohort had a higher cumulative
      incidence of CKD than the control cohort (log-rank test, p value < 0.001).
      Patients with AUD had higher risks of CKD in all the stratified groups, except
      for the subgroup with age over 65 years old. CONCLUSION: Our study suggested that
      AUD was associated with an increased incidence of newly diagnosed CKD by nearly
      two folds. Young age, in particular, had a higher association between AUD and
      CKD. Considering the preventable nature of AUD, establishing effective health
      policies is imperative to reduce high-risk alcohol behaviors and thereby prevent
      alcohol-related kidney disease. Further prospective studies are warranted to
      further elucidate the causation of AUD on kidney function.

PMID- 30188944
TI  - Norovirus interactions with the commensal microbiota.

PMID- 30188945
TI  - Rapid, field-deployable method for collecting and preserving plant metabolome for
      biochemical and functional characterization.
AB  - Study of plant metabolome is a growing field of science that catalogs vast
      biochemical and functional diversity of phytochemicals. However, collecting and
      storing samples of plant metabolome, sharing these samples across the scientific
      community and making them compatible with bioactivity assays presents significant
      challenges to the advancement of metabolome research. We have developed a RApid
      Metabolome Extraction and Storage (RAMES) technology that allows efficient,
      highly compact, field-deployable collection and storage of libraries of plant
      metabolome. RAMES technology combines rapid extraction with immobilization of
      extracts on glass microfiber filter discs. Two grams of plant tissue extracted in
      ethanol, using a specially adapted Dremel(r) rotary tool, produces 25-35 replicas
      of 10 mm glass fiber discs impregnated with phytochemicals. These discs can be
      either eluted with solvents (such as 70% ethanol) to study the metabolomic
      profiles or used directly in a variety of functional assays. We have developed
      simple, non-sterile, anti-fungal, anti-bacterial, and anti-oxidant assays
      formatted for 24-multiwell plates directly compatible with RAMES discs placed
      inside the wells. Using these methods we confirmed activity in 30 out of 32
      randomly selected anti-microbial medicinal plants and spices. Seven species
      scored the highest activity (total kill) in the anti-bacterial (bacteria from
      human saliva) and two anti-fungal screens (Fusarium spp. and Saccharomyces
      cerevisiae), providing functional validation of RAMES technology. RAMES libraries
      showed limited degradation of compounds after 12 months of storage at -20 degrees
      C, while others remained stable. Fifty-eight percent of structures characterized
      in the extracts loaded onto RAMES discs could be eluted from the discs without
      significant losses. Miniaturized RAMES technology, as described and validated in
      this manuscript offers a labor, cost, and time-effective alternative to
      conventional collection of phytochemicals. RAMES technology enables creation of
      comprehensive metabolomic libraries from various ecosystems and geographical
      regions in a format compatible with further biochemical and functional studies.

PMID- 30188948
TI  - Correction: Towards a deeper understanding of parenting on farms: A qualitative
      study.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0198796.].

PMID- 30188949
TI  - Calibration of a density-based model of urban morphogenesis.
AB  - We study a stochastic model of urban growth generating spatial distributions of
      population densities at an intermediate mesoscopic scale. The model is based on
      the antagonist interplay between the two opposite abstract processes of
      aggregation (preferential attachment) and diffusion (urban sprawl). Introducing
      indicators to quantify urban form, the model is first statistically validated and
      intensively explored to understand its complex behavior across the parameter
      space. We then compute real morphological indicators on local areas of size 50km
      covering all European Union, and show that the model can reproduce most of these
      existing urban morphologies. It implies that the morphological dimension of urban
      growth processes at this scale are sufficiently captured by the two abstract
      processes of aggregation and diffusion.

PMID- 30188946
TI  - Pigs that recover from porcine reproduction and respiratory syndrome virus
      infection develop cytotoxic CD4+CD8+ and CD4+CD8- T-cells that kill virus
      infected cells.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) infection is
      difficult to control because the virus undergoes antigenic variation during
      infection and also modulates the protective host immune response. Although
      current vaccines do not provide full protection, they have provided insight into
      the mechanisms of protection. Live PRRSV vaccines induce partial protection
      before the appearance of neutralizing antibody, suggesting cell-mediated immunity
      or other mechanisms may be involved. Herein, we demonstrate recovery from
      infection is associated with development of cytotoxic T-lymphocytes (CTL) that
      can kill PRRSV-infected target cells. Initial experiments showed survival of
      PRRSV-infected monocyte derived macrophage (MDM) targets is reduced when overlaid
      with peripheral blood mononuclear cells (PBMC) from gilts that had recovered from
      PRRSV infection. Further studies with PBMC depleted of either CD4+ or CD8+ T
      cells and positively selected subpopulations of CD4+ and CD8+ T-cells showed that
      both CD4+ and CD8+ T-cells were involved in killing. Examination of killing at
      different time points revealed killing was biphasic and mediated by CTL of
      different phenotypes. CD4+CD8+high were associated with killing target cells
      infected for 3-6 hours. CD4+CD8- CTL were associated with killing at 16-24 hours.
      Thus, all the anti-PRRSV CTL activity in pigs was attributed to two phenotypes of
      CD4+ cells which is different from the anti-viral CD4-CD8+ CTL phenotype found in
      most other animals. These findings will be useful for evaluating CTL responses
      induced by current and future vaccines, guiding to a novel direction for future
      vaccine development.

PMID- 30188947
TI  - Diagnostic delay in extrapulmonary tuberculosis and impact on patient morbidity:
      A study from Zanzibar.
AB  - BACKGROUND: Early and proper treatment of tuberculosis could have an important
      impact on the morbidity, mortality and the economic situation of patients. There
      is insufficient knowledge on the extent of diagnostic delay and the associated
      factors in extrapulmonary tuberculosis (EPTB). The aims of this study were to
      assess the health care seeking behaviour, EPTB knowledge and diagnostic delay in
      presumptive EPTB patients at the main referral hospital in Zanzibar, factors
      associated with longer delay, and the impact of untreated EPTB on self-rated
      health. MATERIALS AND METHODS: Prospective data collection using a semi
      structured questionnaire in patients presenting with symptoms suggestive of EPTB.
      The time between the onset of symptoms and first visit to a health care provider
      (patient delay), and then to the initiation of treatment (health system delay)
      and total delay were analysed according to sociodemographic and clinical factors
      and health care seeking trajectories. The EQ-5D-3L was used among the adult EPTB
      patients to assess the impact of treatment on self-rated health. RESULTS: Of the
      132 patients with median age of 27 years (interquartile range 8-41), 69 were
      categorized as TB cases and 63 as non-TB cases. The median patient, health system
      and total delays were 14, 34 and 62 days respectively, among the EPTB patients. A
      longer health system delay with repeated visits to the same health care level was
      reported. Significantly better self-rated health status was described after
      treatment. The knowledge regarding extrapulmonary disease was low. CONCLUSION:
      Many EPTB patients, presenting to the main referral hospital in Zanzibar,
      experience a long delay in the initiation of treatment, specially patients with
      TB lymphadenitis. The health system delay is the major contributor to the total
      delay. The improvement of self-rated health after treatment implies that timely
      treatment has the potential to reduce morbidity and the economic loss for the
      patient.

PMID- 30188950
TI  - Loneliness predicts a preference for larger interpersonal distance within
      intimate space.
AB  - Loneliness is thought to serve as an adaptive signal indicating the need to
      repair or replace salutary social connections. Accordingly, loneliness may
      influence preferences for interpersonal distance. If loneliness simply motivates
      a desire to socially reconnect, then loneliness may be associated with a
      preference for smaller interpersonal distances. According to the evolutionary
      model of loneliness, however, loneliness also signals an inadequacy of mutual aid
      and protection, augmenting self-preservation motives. If loneliness both
      increases the motivation to reconnect and increases the motivation for self
      protection, then the resulting approach-avoidance conflict should produce a
      preference for larger interpersonal distance, at least within intimate (i.e.,
      proximal) space. Here, we report two survey-based studies of participants'
      preferences for interpersonal distance to distinguish between these competing
      hypotheses. In Study 1 (N = 175), loneliness predicted preferences for larger
      interpersonal distance within intimate space net gender, objective social
      isolation, anxiety, depressive symptomatology, and marital status. In Study 2 (N
      = 405), we replicated these results, and mediation analyses indicated that
      measures of social closeness could not adequately explain our findings. These
      studies provide compelling evidence that loneliness predicts preferences for
      larger interpersonal distance within intimate space, consistent with predictions
      from the evolutionary model of loneliness.

PMID- 30188951
TI  - How fungi defend themselves against microbial competitors and animal predators.

PMID- 30188952
TI  - Right-lateralised lane keeping in young and older British drivers.
AB  - Young adults demonstrate a small, but consistent, asymmetry of spatial attention
      favouring the left side of space ("pseudoneglect") in laboratory-based tests of
      perception. Conversely, in more naturalistic environments, behavioural errors
      towards the right side of space are often observed. In the older population,
      spatial attention asymmetries are generally diminished, or even reversed to
      favour the right side of space, but much of this evidence has been gained from
      lab-based and/or psychophysical testing. In this study we assessed whether
      spatial biases can be elicited during a simulated driving task, and secondly
      whether these biases also shift with age, in line with standard lab-based
      measures. Data from 77 right-handed adults with full UK driving licences (i.e.
      prior experience of left-lane driving) were analysed: 38 young (mean age = 21.53)
      and 39 older adults (mean age = 70.38). Each participant undertook 3 tests of
      visuospatial attention: the landmark task, line bisection task, and a simulated
      lane-keeping task. We found leftward biases in young adults for the landmark and
      line bisection tasks, indicative of pseudoneglect, and a mean lane position
      towards the right of centre. In young adults the leftward landmark task biases
      were negatively correlated with rightward lane-keeping biases, hinting that a
      common property of the spatial attention networks may have influenced both tasks.
      As predicted, older adults showed no group-level spatial asymmetry on the
      landmark nor the line bisection task, but they maintained a mean rightward lane
      position, similar to young adults. The 3 tasks were not inter-correlated in the
      older group. These results suggest that spatial biases in older adults may be
      elicited more effectively in experiments involving complex behaviour rather than
      abstract, lab-based measures. More broadly, these results confirm that lateral
      biases of spatial attention are linked to driving behaviour, and this could prove
      informative in the development of future vehicle safety and driving technology.

PMID- 30188953
TI  - Chronic obstructive pulmonary disease with short-acting inhaled pharmacotherapy
      increases the risk of prostate cancer: A two-stage database approach.
AB  - BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) are at a
      higher risk of many types of cancer. However, specific investigation of the risk
      of prostate cancer and the influence of COPD pharmacotherapy in patients with
      COPD is lacking. This study investigated the risk and influence of COPD
      pharmacotherapy on risk of prostate cancer in patients with COPD. METHODS: This
      retrospective cohort study used data from Taiwan's Longitudinal Health Insurance
      Database 2005 (LHID2005). The study cohort comprised COPD patients who received
      treatment between 2004 and 2008, and who were identified from the LHID2005. The
      control cohort comprised patients without COPD and was matched to the study
      cohort by age and sex. Two-stage propensity score calibration with the National
      Health Interview Survey 2005 was performed to obtain the missing confounders of
      smoking, alcohol drinking, and body mass index in the LHID. The hazard ratio (HR)
      and adjusted HR were estimated. Moreover, the influence of inhaled medications
      and other related medication on the risk of prostate cancer was analyzed by Cox
      proportional hazard regression. RESULTS: The COPD cohort comprised 12,774
      patients, and the control cohort comprised 38,322 patients (1:3). The incidence
      of prostate cancer was 633 per 100,000 person-years in the COPD cohort and 361
      per 100,000 person-years in the control cohort. The propensity score calibration
      adjusted HR was 1.62 (95% CI, 1.40-1.87, p < 0.001) in the COPD cohort. Further
      analysis revealed that the adjusted HR for the risk of prostate cancer was 1.61
      (95% CI, 1.19-2.16, p = 0.002) in patients with COPD who used short-acting
      muscarinic antagonists (SAMAs) and 1.89 (95% CI, 1.40-2.54, p < 0.001) in
      patients with COPD who used short-acting beta-agonists (SABAs). COPD patients had
      lower risk of prostate cancer when using statin (HR = 0.63, 95% CI, 0.45-0.89, p
      = 0.010) or aspirin (HR = 0.55, 95% CI, 0.35-0.85, p = 0.008). CONCLUSION:
      Patients with COPD are at a higher risk of prostate cancer, particularly those
      using SAMAs or SABAs. This finding suggests that inflammation control may be an
      effective strategy for decreasing the risk of prostate cancer.

PMID- 30188955
TI  - Reality check of using the surgical safety checklist: A qualitative study to
      observe application errors during snapshot audits.
AB  - BACKGROUND: The WHO Surgical Safety Checklist (SSC) was established to address
      important safety issues and to reduce the number of surgical deaths. So far,
      numerous reports have demonstrated sub-optimal implementation of the SSC in
      practice and limited improvements in patient outcomes. Therefore, the aim of this
      study was to audit the SSC-practice in a real-world setting in a university
      hospital setting. METHODS: From 2015 to 2016, independent observers performed
      snapshot audits in operating theatres and shadowed the three phases of the SSC.
      Using a 4-point Likert-scale to rate the compliance on each audit day, we
      generated a report highlighting possible improvements and provided feedback to
      the operating team members. RESULTS: Audits were performed on 36 operating days
      (2015: n = 19; 2016: n = 17), in which a total of 136 surgical interventions were
      observed. Overall, the percentage of "very good compliance" improved from 2015 to
      2016: for the sign-in from 52.9% to 81.2% (p = 0.141), for the team-time-out from
      33.3% to 58.8% (p = 0.181), and for the sign-out from 21.4% to 41.7% (p = 0.401).
      The qualitative review revealed inconsistencies when applying the SSC, of which
      the missing documentation of an actually performed item or the wrong timing for
      an item was most common. CONCLUSION: Snapshot audits revealed that SSC compliance
      has improved over the observed period, while its application revealed
      inconsistencies during the three phases of the SSC. Snapshot audits proved to be
      a valuable tool in the qualitative analysis of SSC compliance and gave more
      insight than a mere completeness check of ticks in SSC documents.

PMID- 30188954
TI  - Cellular sheddases are induced by Merkel cell polyomavirus small tumour antigen
      to mediate cell dissociation and invasiveness.
AB  - Merkel cell carcinoma (MCC) is an aggressive skin cancer with a high propensity
      for recurrence and metastasis. Merkel cell polyomavirus (MCPyV) is recognised as
      the causative factor in the majority of MCC cases. The MCPyV small tumour antigen
      (ST) is considered to be the main viral transforming factor, however potential
      mechanisms linking ST expression to the highly metastatic nature of MCC are yet
      to be fully elucidated. Metastasis is a complex process, with several discrete
      steps required for the formation of secondary tumour sites. One essential trait
      that underpins the ability of cancer cells to metastasise is how they interact
      with adjoining tumour cells and the surrounding extracellular matrix. Here we
      demonstrate that MCPyV ST expression disrupts the integrity of cell-cell
      junctions, thereby enhancing cell dissociation and implicate the cellular
      sheddases, A disintegrin and metalloproteinase (ADAM) 10 and 17 proteins in this
      process. Inhibition of ADAM 10 and 17 activity reduced MCPyV ST-induced cell
      dissociation and motility, attributing their function as critical to the MCPyV
      induced metastatic processes. Consistent with these data, we confirm that ADAM 10
      and 17 are upregulated in MCPyV-positive primary MCC tumours. These novel
      findings implicate cellular sheddases as key host cell factors contributing to
      virus-mediated cellular transformation and metastasis. Notably, ADAM protein
      expression may be a novel biomarker of MCC prognosis and given the current
      interest in cellular sheddase inhibitors for cancer therapeutics, it highlights
      ADAM 10 and 17 activity as a novel opportunity for targeted interventions for
      disseminated MCC.

PMID- 30188956
TI  - Improving health worker performance through text messaging: A mixed-methods
      evaluation of a pilot intervention designed to increase coverage of intermittent
      preventive treatment of malaria in pregnancy in West Nile, Uganda.
AB  - Poor health worker performance is a well-documented obstacle to quality service
      provision. Due to the increasingly widespread availability of mobile devices,
      mobile health (mHealth) has received growing attention as a service improvement
      tool. This pilot study explored feasibility, acceptability and outcomes of an
      mHealth intervention designed to increase coverage of intermittent preventive
      treatment of malaria in pregnancy (IPTp) in two districts of West Nile, Uganda.
      In both districts, selected health workers (N = 48) received classroom training
      on malaria in pregnancy. All health workers in one district (N = 49) subsequently
      received 24 text messages reinforcing the training content. The intervention was
      evaluated using a mixed-methods approach, including four focus group discussions
      with health workers and three in-depth interviews with district health officials,
      health worker knowledge assessments one month (N = 90) and six months (N = 89)
      after the classroom training, and calculation of IPTp coverage from participating
      health facilities' (N = 16) antenatal care registers covering six months pre- and
      post-intervention. Complementing classroom training with text messaging was found
      to be a feasible, acceptable and inexpensive approach to improving health worker
      performance. The messages served as reminders to those who had attended the
      classroom training and helped spread information to those who had not. Health
      workers in the district where text messages were sent had significantly better
      knowledge of IPTp, achieving an increased composite knowledge score of 6.00
      points (maximum score: 40) compared with those in the district where only
      classroom training was provided. Average facility coverage of three doses of IPTp
      was also significantly higher where text messages were sent (85.8%) compared with
      the district where only classroom training was provided (54.1%). This
      intervention shows promise for the improvement of health worker performance for
      delivery of IPTp, and could have significant broader application.

PMID- 30188957
TI  - Landiolol for rate control management of atrial fibrillation in patients with
      cardiac dysfunction.
AB  - Atrial fibrillation (AFib) is frequently associated with heart failure.
      Guidelines for AFib management have been recently updated and include an
      algorithm for acute heart rate control based on left ventricular ejection
      fraction and haemodynamics. Landiolol is an injectable ultra-short beta-blocker
      with very high beta-1 selectivity, listed in Japanese Guidelines for AFib
      management as potential option for rate control of patient with heart failure.
      Landiolol is now available in Europe with indication of controlling heart rate in
      AFib and supraventricular tachycardia. This review discusses existing clinical
      data in Japan and perspectives of landiolol use for acute rate control of AFib
      patients with cardiac dysfunction.

PMID- 30188958
TI  - Landiolol for managing post-operative atrial fibrillation.
AB  - Beta-blockers are a potential option to manage peri-operative atrial
      fibrillation. Landiolol is a new ultra-short beta-blocker with a half-life of
      only 4 minutes and very high beta-1 selectivity which has been used for treatment
      and prevention of atrial fibrillation in pulmonary surgery and gastro-intestinal
      surgery. Due to its limited negative inotropic effect and high beta-1 selectivity
      landiolol allows for control of heart rate with minimal impact on blood pressure.
      Landiolol is well tolerated by the respiratory system. Additional benefits are
      related to the regulation of the inflammatory response and blunting of the
      adrenergic pathway. There is a limited number of trials with total of 61 patients
      undergoing lung resection or oesophagectomy who developed post-operative atrial
      fibrillation and were treated with landiolol. The experience with landiolol for
      prevention is more documented than landiolol application for treatment of post
      operative atrial fibrillation. There are 9 comparative studies with a total of
      450 patients administered landiolol for prevention of post-operative atrial
      fibrillation. The use of low dosage (5-10mcg/kg/min) is usually sufficient to
      rapidly control heart rate which is associated with earlier and higher rate of
      conversion to sinus rhythm as compared to the controls. The excellent tolerance
      of landiolol at lower dosage (3-5mcg/kg/min) allows to initiate prophylactic use
      during surgery and postoperatively. Landiolol prophylaxis is associated with
      reduced incidence of post-operative atrial fibrillation without triggering
      adverse events related to a beta-blockade.

PMID- 30188959
TI  - Landiolol: pharmacology and its use for rate control in atrial fibrillation in an
      emergency setting.
AB  - This article provides new insight on landiolol, an ultra-short acting injectable
      betablocker, recently approved in Europe, with regard to its pharmacokinetic and
      pharmacodynamic profile, along with its first experience in Caucasian healthy
      volunteers and patients with atrial fibrillation. Landiolol as iv formulation
      exhibited in an emergency setting rapid rate reduction in patients with
      tachycardic atrial fibrillation without pronounced blood pressure drop both in
      caucasian and asian populations in similar manner.

PMID- 30188960
TI  - Landiolol for managing atrial fibrillation in intensive care.
AB  - Landiolol is an injectable ultrashort acting beta-blocker with high beta1
      selectivity indicated for heart rate control of atrial fibrillation in the
      emergency and critical care setting. Accordingly, landiolol is associated with a
      significantly reduced risk of arterial hypotension and negative inotropic
      effects. Based on this particular profile along with the clinical experience in
      Japan for more than a decade landiolol represents a promising agent for the
      management of elevated heart rate and atrial fibrillation in intensive care
      patients even with catecholamine requirements. This article provides a review and
      perspective of landiolol for heart rate control in intensive care patients based
      on the current literature.

PMID- 30188962
TI  - Association between RBMS1 gene rs7593730 and BCAR1 gene rs7202877 and Type 2
      diabetes mellitus in the Chinese Han population.
AB  - Two recent studies found that RBMS1 gene rs7593730 and BCAR1 gene rs7202877 are
      related to type 2 diabetes. However, the association of these loci with type 2
      diabetes mellitus (T2DM) has not been examined in Chinese. We performed a
      replication study to investigate the association of the 2 susceptibility loci
      with T2DM in the Chinese population. We genotyped 1961 Chinese participants (991
      with T2DM and 970 controls) for each of the 2 single nucleotide polymorphisms
      (SNPs) rs7593730 in RBMS1 and rs7202877 near BCAR1 using SNPscan and examined
      their association with T2DM using logistic regression analysis. We also analyzed
      the correlation of the SNP alleles and clinical phenotypes. In additive model,
      genotype association analysis of BCAR1 rs7202877 loci revealed that the
      homozygous of rs7202877 GG carriers had significantly decreased T2DM risk
      compared to homozygous carriers of TT (P=0.038, OR 0.44, 95% CI 0.20-0.96). In
      the recessive model, the GG genotype GG had significantly decreased T2DM risk
      compared to GT+TT (P=0.043, OR 0.67, 95% CI 0.46-0.99). Allele G was
      statistically significantly correlated with TC (mmol/L) (P=0.036) and LDL-C
      (mmol/L) (P=0.007). As for rs7593730, the carriers of CT and TT genotype had
      significantly decreased T2DM risk compared to the carriers of CC genotype (CT: CC
      P=0.038, OR 0.71, 95% CI 0.51-0.98; TT: CC P=0.010, OR 0.32, 95% CI 0.13-0.76).
      In a dominant model, TT+CT: CC (P=0.013, OR 0.673, 95% CI 0.49-0.92) and in a
      recessive model, TT: CT+CC (P=0.019, OR 0.59, 95% CI 0.39-0.92). The T allele
      carriers had significantly decreased T2DM risk compared to the carriers of C
      (P=0.002, OR 0.65, 95% CI 0.50-0.86). Allele T was statistically correlated with
      FINS (P=0.010). In conclusion, our study showed that RBMS1 gene rs7593730 and
      BCAR1 gene rs7202877 were significantly associated with type 2 diabetes in the
      Chinese population.

PMID- 30188961
TI  - Landiolol for managing atrial fibrillation in post-cardiac surgery.
AB  - Landiolol is an intravenous ultra-short acting beta-blocker which has been used
      in Japan for many years to prevent and/or to treat post-operative atrial
      fibrillation following cardiac surgery. The drug is now available in Europe. This
      article is a systematic review of literature regarding the use of landiolol in
      that specific surgical setting.

PMID- 30188963
TI  - Characterization of an acidic alpha-galactosidase from hemp (Cannabis sativa L.)
      seeds and its application in removal of raffinose family oligosaccharides (RFOs).
AB  - An acidic alpha-galactosidase designated as hemp seed alpha-galactosidase (HSG)
      was purified from hemp (Cannabis sativa L.) seeds. By means of chromatographic
      procedures which involved chromatography on the cation-exchangers CM-cellulose
      and SP-Sepharose, chromatography on the anion-exchangers DEAE-cellulose and Q
      Sepharose, and gel filtration on Superdex 75 using fast protein liquid
      chromatography, HSG was purified to electrophoretic homogeneity. Results of SDS
      PAGE and gel filtration on FPLC Superdex 75 revealed that the enzyme was a
      monomeric protein with a molecular weight of 38 kDa. Sequences of the inner
      peptides of the alpha-galactosidase obtained by MALDI-TOF-MS showed that HSG was
      a novel alpha-galactosidase since there was a little similarity to the majority
      of alpha-galactosidases recorded in the literature. A pH of 3.0 and a temperature
      of 50 degrees C were optimal for the activity of the enzyme. The activity of HSG
      was inhibited by the chemical modification with N-bromosuccinimide (NBS) reagent.
      HSG contained 16 tryptophan residues and two tryptophan residues on the surface,
      which were crucial to the alpha-galactosidase activity. The heavy metal ions
      Cd2+, Cu2+, Hg2+ and Zn2+ inhibited its activity. The Km and Vmax for the
      hydrolysis of pNPGal (4-nitrophenyl alpha-D-galactopyranoside) were respectively
      0.008 mM and 68 MUM min-1 mg-1. HSG also catalyzed the hydrolysis of raffinose
      and other natural substrates. Hence the alpha-galactosidase possesses a
      tremendous potential for food and feed industries in the elimination of
      indigestible oligosaccharides from leguminous products.

PMID- 30188964
TI  - Overexpression of zeaxanthin epoxidase gene from Medicago sativa enhances the
      tolerance to low light in transgenic tobacco.
AB  - Zeaxanthin epoxidase (ZEP) plays an important role in xanthophyll cycle which is
      a process closely related to photosynthesis. However, an impact of ZEP on low
      light stress has not been studied. In this study, the functions of an alfalfa
      (Medicago sativa) zeaxanthin epoxidase gene, MsZEP, in response to low-light
      stress were investigated by heterologous expression in tobacco (Nicotiana
      tabacum). Under normal light conditions, the measured parameters were not
      significantly different between transgenic and wild-type (WT) plants except for
      non-photochemical quenching value and chlorophyll a content. However, the
      differences were detected under low-light stress. We found that MsZEP
      overexpression tobacco grew faster than WT (p<=0.05). The leaf fresh weight and
      leaf area of transgenic plants were significantly higher, and the number of
      stomata was greater in MsZEP-overexpression tobacco. As for photosynthetic
      characteristics, quantum yield of PSII (PhiPSII) and maximal photochemical
      efficiency of PSII (Fv/Fm) were not significantly different, whereas non
      photochemical quenching (NPQ), net photosynthetic rate (Pn), stomatal conductance
      (Gs) and transpiration rate (Tr) of MsZEP-overexpression tobacco were
      significantly higher than in WT plants. However, no significant difference was
      detected between the two types of tobacco in chlorophyll and carotenoids content.
      In conclusion, MsZEP can improve the ability of tobacco to withstand low-light
      stress, which might be due to its stronger photosynthetic activity and the
      improvement of stomatal density under low light.

PMID- 30188965
TI  - Ezetimibe prevents myocardial remodeling in an obese rat model by inhibiting
      inflammation.
AB  - Inflammation plays an important role in the development of many obesity-related
      diseases. This study aimed to investigate the effect of ezetimibe on inflammation
      and myocardial remodeling in obese rats. A rat model of obesity was established,
      and myocardial damage was examined by transmission electron microscopy and Masson
      staining. Twenty obese rats were divided into two groups (n=10): obese group and
      ezetimibe group. Ten SD rats were used as controls. Western blot was performed to
      monitor the expression of P-p38MAPK and interleukin (IL)-6. Immunohistochemical
      staining was used to monitor the expression of intercellular adhesion molecule-1
      and vascular cell adhesion molecule-1. In the obese rats group, we observed
      increased inflammatory factors and myocardial hypertrophy. In contrast, the
      ezetimibe group exhibited decreased expression of inflammatory factors and an
      improvement in myocardial remodeling compared to the obese group.
      Mechanistically, we found that ezetimibe decreased P-p38MAPK, IL-6, intercellular
      adhesion molecule-1, and vascular cell adhesion molecule-1 levels in the hearts
      of the obese rats. Taken together, these results indicate that ezetimibe may
      improve myocardial remodeling in obese rats by inhibiting inflammation.

PMID- 30188966
TI  - miR-23b promotes cutaneous wound healing through inhibition of the inflammatory
      responses by targeting ASK1.
AB  - Wound healing is a complicated event that develops in three overlapping phases:
      inflammatory, proliferative, and remodeling. MicroRNAs (miRNAs) have been proved
      to play an important role in the healing process of skin trauma, and alteration
      of specific miRNA expression during different phases may be associated with
      abnormal wound healing. In this study, we determined the variation of miR-23b
      expression after trauma in normal mice and in cultured cells exposed to
      lipopolysaccharide. We further demonstrated that excessive miR-23b could
      significantly accelerate wound healing in vivo. Up-regulation of miR-23b
      decreases infiltration of inflammatory cells, as evidenced by pathologic
      staining. Meanwhile, miR-23b could significantly inhibit the expression of pro
      inflammatory cytokines, including TNF-alpha, IL-1beta, IL-6, and Ccl2, and
      significantly increase anti-inflammatory factor IL-10. Furthermore, miR-23b could
      also promote alpha-SMA expression in a fiber pattern and increase the expression
      of Col1a1 and Col3a1. Importantly, we also showed that miR-23b could inhibit
      inflammation to promote wound healing by targeting apoptotic signal-regulating
      kinase 1 (ASK1). Notably, knockdown of ASK1 could reduce inflammation factor
      expression in vitro. Together, our data reveal that miR-23b is a potent
      therapeutic agent for cutaneous wound healing that shortens the period of
      inflammatory responses and promotes keratinocyte migration for the re
      epithelialization of wound sites.

PMID- 30188967
TI  - Fam198a, a member of secreted kinase, secrets through caveolae biogenesis
      pathway.
AB  - Fam198a is a member of four-jointed protein kinases, a secreted protein kinase
      family. It was identified as a caveolae-associated protein and colocalized with
      cavin-1 and caveolin-1 in both tissues and cells. The newly synthesized Fam198a
      precursor in endoplasmic reticulum (ER) was transported by caveolae biogenesis
      vesicles to Golgi apparatus in which it was proteolytically cleaved into the
      secreted mature form. The amino acid mutation analysis identified Arg 120 and 437
      as the proteolytic sites in Fam198a precursor during maturation. In mouse embryo
      fibroblasts (MEFs) obtained from cavin-1-/- or caveolin-1-/- mice, Fam198a
      precursor was retained in ER and no mature Fam198a could be formed in these
      cells. Ectopic expression of exogenous cavin-1 in cavin-1-/- MEFs restored the
      blocked Fam198a post-translational process and secretion. Cavin-1 was also
      required for Fam198a secretion after its maturation in Golgi apparatus. Ectopic
      expression of cavin-1 in A549 cells restored the blocked Fam198a secretion. These
      results suggest that protein secretion is an important function for caveolae
      biogenesis pathway and the disruption of caveolae system will affect those
      functions played by the secreted proteins.

PMID- 30188968
TI  - Estimating the Short-Term Effects of the Earned Income Tax Credit on Child
      Health.
AB  - The Earned Income Tax Credit (EITC) is the largest US poverty-alleviation
      program, yet few studies examine its effects on the health of recipients'
      children. We employed quasiexperimental techniques to test the hypothesis that
      EITC refund receipt is associated with short-term improvements in child health.
      The data set included children in families surveyed in the Third National Health
      and Nutrition Examination Survey (n = 7,444). We employed a difference-in
      differences approach, exploiting the seasonal nature of EITC refund receipt. We
      compared children of EITC-eligible families interviewed immediately after refund
      receipt (February to April) with those interviewed during other months (May to
      January), differencing out seasonal variation among non-EITC-eligible families.
      We examined outcomes that were likely to be affected immediately after refund
      receipt, including general health, nutrition, metabolic and inflammatory
      biomarkers, and test scores. There were improvements in physician-reported
      overall health after refund receipt but no changes in infection, serum metabolic
      or inflammatory markers, or test scores, and there were contradictory findings
      for food insufficiency. In summary, EITC refunds are not strongly associated with
      most short-term health outcomes among recipients' children, although numerous
      previous studies have demonstrated impacts on longer-term outcomes. This
      highlights the importance of examining the effects of public policies on
      beneficiaries and their children using varying study designs.

PMID- 30188969
TI  - Invited Commentary: Detecting Individual and Global Horizontal Pleiotropy in
      Mendelian Randomization-A Job for the Humble Heterogeneity Statistic?
AB  - Mendelian randomization (MR) is gaining in recognition and popularity as a method
      for strengthening causal inference in epidemiology by utilizing genetic variants
      as instrumental variables. Concurrently with the explosion in empirical MR
      studies, there has been the steady production of new approaches for MR analysis.
      The recently proposed "global and individual tests for direct effects" (GLIDE)
      approach fits into a family of methods that aim to detect horizontal pleiotropy
      at the individual single nucleotide polymorphism level and at the global level
      and to adjust the analysis by removing outlying single nucleotide polymorphisms.
      In this commentary, we explain how existing methods can (and indeed are) being
      used to detect pleiotropy at the individual and global levels, although not
      explicitly using this terminology. By doing so, we show that the true comparator
      for GLIDE is not MR-Egger regression (as Dai et al., the authors of the
      accompanying article (Am J Epidemiol. 2018;187(12):2672-2680), claim) but rather
      the humble heterogeneity statistic.

PMID- 30188970
TI  - A Population-based Matched Sibling Analysis Estimating the Association between
      First Interpregnancy Interval and Birth Outcomes.
AB  - The association between a single interpregnancy interval (IPI) on birth outcomes
      has not yet been explored using matched methods. We modelled the odds of preterm
      birth, small-for-gestational age and low birthweight in a second, liveborn infant
      in a cohort of 192,041 sibling pairs born in Western Australia between 1980 and
      2010. The association between IPI and birth outcomes was estimated from the
      interaction between birth order and IPI (with 18-23 months as the reference
      category), using conditional logistic regression. Matched analysis showed the
      odds of preterm birth were higher for siblings born following an IPI <6 month
      (adjusted Interaction Odds Ratio [IOR]: 1.22; 95% CI: 1.06, 1.38) compared with
      18-23 month IPI. There were no significant differences for IPI <6 months for
      other outcomes (small-for-gestational age or low birthweight). This is the first
      study to use matched analyses to investigate the association between a single IPI
      on birth outcomes. IPI <6 months were associated with increased odds of preterm
      birth in secondborn infants, although the association is likely smaller than
      previously estimated by unmatched studies.

PMID- 30188972
TI  - A systematic review, meta-analysis and meta-regression of the prevalence of
      protein-energy malnutrition: associations with geographical region and sex.
AB  - Background: protein-energy malnutrition is a major health concern in home
      dwelling older adults, particularly in the context of an ageing population.
      Therefore, a systematic review and meta-analysis was undertaken to determine the
      prevalence of malnutrition among older adults living independently in the
      community according to geographical region, sampling frame, rurality and sex.
      Methods: six electronic databases were searched until September 2016. Original
      research studies which used the Mini Nutritional Assessment, Patient-Generated
      Subjective Global Assessment or Subjective Global Assessment to determine
      nutrition status in community samples with a mean age of >=65 years were
      critically appraised and pooled using meta-analysis. Meta-regression was used to
      explore predictors of malnutrition prevalence in pooled statistics with high
      heterogeneity. Results: 111 studies from 38 countries (n = 69,702 participants)
      were included. The pooled prevalence of malnutrition in the older community
      setting ranged from 0.8% (95% CI: 0.2-1.7%) in Northern Europe to 24.6% (95% CI:
      0.0-67.9%) in South-East Asia. Of all sampling frames, participants receiving
      homecare services had the highest prevalence at 14.6% (95% CI: 9.9-20.0%).
      Malnutrition prevalence in rural communities (9.9%; 95% CI: 4.5-16.8%) was double
      that in urban communities (5.7%; 95% CI: 4.2-7.3%) and higher among females than
      males (odds ratio = 1.45 [95% CI: 1.27-1.66]; P < 0.00001). Conclusions: the
      results of this review provide strategic insight to develop public and community
      health priorities for preventing malnutrition and associated poor health
      outcomes.

PMID- 30188974
TI  - Commentary on Tayob and Murray (2014) with a useful update pertaining to study
      design.

PMID- 30188973
TI  - Impaired proinflammatory response in stringently defined otitis prone children
      during viral upper respiratory infections.
AB  - Background: Viral upper respiratory tract infection (URI) is common and often
      precipitates acute otitis media (AOM) caused by bacterial otopathogens in young
      children. Acute inflammatory responses initiated in the early phase of viral URI
      contribute to preventing the development of AOM. Our group has been studying
      stringently defined otitis prone (sOP) children who are susceptible to recurrent
      AOM. Methods: Here we assessed proinflammatory cytokine and chemokine levels in
      the nasopharynx of sOP children during a clinically diagnosed viral URI compared
      to non-otitis prone (NOP) children. We also examined the difference of the
      nasopharyngeal (NP) responses between viral URI events and the following AOM
      episodes in both sOP and NOP children. Results: sOP children exhibited
      significantly more AOM episodes per child (8.86 fold higher than NOP children
      did), and viral URI (P < 0.0001) and viral URI followed by AOM (P < 0.0001) than
      NOP children. sOP children had lower nasal proinflammatory levels of IL-6 (P =
      0.05), IL-10 (P = 0.001), TNF-alpha (P = 0.004), and RANTES (P = 0.002) than NOP
      children during viral URI. NOP children had higher levels of IL-6 (P = 0.02), IL
      10 (P = 0.02), IFN-gamma (P = 0.003), TNF-alpha (P = 0.006), IL-1beta (P =
      0.022), MCP-1 (P = 0.028), RANTES (P = 0.005), IL-2 (P = 0.002), IL-17 (P =
      0.007) during viral URI vs. AOM following the URI compared to sOP children.
      Conclusion: We conclude that sOP children have more frequent viral URIs than NOP
      children due to deficient antiviral NP proinflammatory cytokine and chemokine
      responses.

PMID- 30188971
TI  - Diagnostics for Pleiotropy in Mendelian Randomization Studies: Global and
      Individual Tests for Direct Effects.
AB  - Diagnosing pleiotropy is critical for assessing the validity of Mendelian
      randomization (MR) analyses. The popular MR-Egger method evaluates whether there
      is evidence of bias-generating pleiotropy among a set of candidate genetic
      instrumental variables. In this article, we propose a statistical method-global
      and individual tests for direct effects (GLIDE)-for systematically evaluating
      pleiotropy among the set of genetic variants (e.g., single nucleotide
      polymorphisms (SNPs)) used for MR. As a global test, simulation experiments
      suggest that GLIDE is nearly uniformly more powerful than the MR-Egger method. As
      a sensitivity analysis, GLIDE is capable of detecting outliers in individual
      variant-level pleiotropy, in order to obtain a refined set of genetic
      instrumental variables. We used GLIDE to analyze both body mass index and height
      for associations with colorectal cancer risk in data from the Genetics and
      Epidemiology of Colorectal Cancer Consortium and the Colon Cancer Family Registry
      (multiple studies). Among the body mass index-associated SNPs and the height
      associated SNPs, several individual variants showed evidence of pleiotropy.
      Removal of these potentially pleiotropic SNPs resulted in attenuation of
      respective estimates of the causal effects. In summary, the proposed GLIDE method
      is useful for sensitivity analyses and improves the validity of MR.

PMID- 30188975
TI  - Promise and Pitfalls of the Sibling Comparison Design in Studies of Optimal Birth
      Spacing.
AB  - Numerous observational studies have shown that infants born after short
      interpregnancy intervals (the interval between birth and subsequent conception)
      are more likely to experience adverse perinatal outcomes than infants born
      following longer intervals. Yet, it remains controversial whether the link
      between short interpregnancy interval and adverse outcomes is causal, or
      confounded by factors such as low socio-economic position, inadequate access to
      healthcare, and unintended pregnancy. Sibling comparison studies, which use a
      woman as her own control by comparing exposure and outcome status of her
      different pregnancies (i.e., comparing sibling offspring), have gained popularity
      as a strategy to reduce confounding by these difficult-to-measure factors that
      are nevertheless relatively stable within women. A variant of the design, used by
      Regan et al. in this issue (Am J Epidemiol 2018;XX:XXX-XXX), is a maternally
      matched design based on a single interpregnancy interval per woman. Using real
      and simulated data, we highlight underappreciated shortcomings of these designs
      that may limit the validity of study findings. In particular, we illustrate how
      the single-interval variant appears to derive estimates from comparisons between
      different mothers, not within mothers. Future studies of optimal birth spacing
      using sibling comparison designs should examine in detail the potential
      consequences of these methodological limitations.

PMID- 30188976
TI  - Pharmacodynamic Analysis of Daptomycin-Treated Enterococcal Bacteremia: It Is
      Time to Change the Breakpoint.
AB  - Background: Currently, there is debate that the daptomycin susceptibility
      breakpoint (i.e., minimum inhibitory concentration, MIC, <=4 mg/L) is
      inappropriate for application to serious enterococcal infections. Observational
      data support prescription of high doses (>8 mg/kg/day) in the treatment of
      bacteremia. Pharmacodynamic targets associated with positive patient outcomes,
      however, remain undefined. Methods: Data were pooled from observational studies
      assessing outcomes in daptomycin-treated enterococcal bacteremia. Patients who
      received an additional antibiotic with activity against enterococci and/or a beta
      lactam antibiotic at any time during treatment were excluded. Daptomycin
      exposures were calculated using a published population pharmacokinetic model. The
      free drug area under the concentration-time curve to MIC ratio (fAUC/MIC)
      threshold predictive of 30-day survival was identified by classification and
      regression tree (CART) analysis and confirmed with multivariable logistic
      regression. Monte Carlo simulations determined the probability of target
      attainment (PTA) at clinically relevant MICs. Results: Of 114 patients that
      received daptomycin monotherapy, 67 (58.8%) were alive at 30 days. Stratifying
      the cohort by severity of illness, a fAUC/MIC >27.43 was associated with survival
      in low-acuity (N=77) patients (68.9 versus 37.5%, p=0.006), which remained
      significant (p=0.026) after adjusting for infection source and immunosuppression.
      The PTA for a 6 mg/kg/day dose was 1.5-5.5% when MIC=4 mg/L (i.e., daptomycin
      susceptible) and 91.0-97.9% when MIC=1 mg/L. Conclusions: For enterococcal
      bacteremia, a daptomycin fAUC/MIC >27.43 was associated with 30-day survival
      among low-acuity patients. As pharmacodynamics for the approved dose are
      optimized only when MIC <=1 mg/L, these data continue to stress the importance of
      re-evaluation of the current susceptibility breakpoint.

PMID- 30188977
TI  - Gastrointestinal stromal tumours: ESMO-EURACAN Clinical Practice Guidelines for
      diagnosis, treatment and follow-up.

PMID- 30188978
TI  - Pharmacokinetics, safety and efficacy of an allometric miltefosine regimen for
      the treatment of visceral leishmaniasis in Eastern African children: an open
      label, phase-II clinical trial.
AB  - Background: Convenient, safe, and effective treatments for visceral leishmaniasis
      in Eastern African children are lacking. Miltefosine, the only oral treatment,
      failed to achieve adequate cure rates in Eastern Africa, particularly in
      children, in whom linear dosing (2.5 mg/kg/day for 28 days) resulted in 59% cure
      rate, with lower systemic miltefosine exposure than in adults. Methods: We
      conducted a phase-II trial in Kenya and Uganda in 30 children, aged 4-12 years,
      with visceral leishmaniasis, to test whether 28 days of allometric miltefosine
      dosing is able to safely achieve a higher and more effective systemic exposure of
      miltefosine than linear dosing (historical data). Results: Miltefosine
      accumulated during treatment. Median AUC0-210 and Cmax values were slightly
      higher than those reported previously for children on linear dosing but not dose
      proportionally. Miltefosine exposure at start of treatment was increased, with
      higher median day-7 plasma concentrations (5.88 vs 2.67 ug/mL). Concentration
      time curves were less variable, avoiding the low levels of exposure observed with
      linear dosing. The 210-day cure rate was 90% (95% confidence interval, 73%-98%),
      similar to that previously described in adults. Nineteen miltefosine-treatment
      related adverse events (AEs) occurred but none caused treatment discontinuation.
      Two serious AEs occurred, both unrelated to treatment and fully recovering.
      Conclusions: Allometric miltefosine dosing achieved increased and less variable
      exposure than linear dosing, though not reaching the expected exposure levels.
      The new dosing regimen safely increased the efficacy of miltefosine for Eastern
      African children with visceral leishmaniasis. Further development of miltefosine
      should adopt allometric dosing in paediatric patients.

PMID- 30188979
TI  - Targeting myeloperoxidase in inflammatory atherosclerosis.

PMID- 30188981
TI  - Accuracy of 0/1-hour algorithm for diagnosis of MI in the elderly: mono
      dimensional optimization of troponin cut-offs for individual confounders or
      precision medicine?

PMID- 30188980
TI  - De novo transcriptome sequencing and metabolite profiling analyses reveal the
      complex metabolic genes involved in the terpenoid biosynthesis in Blue Anise Sage
      (Salvia guaranitica L.).
AB  - Many terpenoid compounds have been extracted from different tissues of Salvia
      guaranitica. However, the molecular genetic basis of terpene biosynthesis
      pathways is virtually unknown. In this study, approximately 4 Gb of raw data were
      generated from the transcriptome of S. guaranitica leaves using Illumina HiSeq
      2000 sequencing. After filtering and removing the adapter sequences from the raw
      data, the number of reads reached 32 million, comprising 186 million of high
      quality nucleotide bases. A total of 61,400 unigenes were assembled de novo and
      annotated for establishing a valid database for studying terpenoid biosynthesis.
      We identified 267 unigenes that are putatively involved in terpenoid metabolism
      (including, 198 mevalonate and methyl-erythritol phosphate (MEP) pathways,
      terpenoid backbone biosynthesis genes and 69 terpene synthases genes). Moreover,
      three terpene synthase genes were studied for their functions in terpenoid
      biosynthesis by using transgenic Arabidopsis; most transgenic Arabidopsis plants
      expressing these terpene synthetic genes produced increased amounts of terpenoids
      compared with wild-type control. The combined data analyses from the
      transcriptome and metabolome provide new insights into our understanding of the
      complex metabolic genes in terpenoid-rich blue anise sage, and our study paves
      the way for the future metabolic engineering of the biosynthesis of useful
      terpene compounds in S. guaranitica.

PMID- 30188982
TI  - Rupture of the papillary muscle: a rare complication during percutaneous
      transvenous mitral commissurotomy successfully treated by surgical mitral valve
      replacement.

PMID- 30188983
TI  - Collecting Nontarget Wood-Boring Insects for Host-Specificity Testing of Natural
      Enemies of Cerambycids: A Case Study of Dastarcus helophoroides (Coleoptera:
      Bothrideridae), a Parasitoid of the Asian Longhorned Beetle (Coleoptera:
      Cerambycidae).
AB  - We describe approaches to addressing the perennial challenge of collecting a
      sufficient diversity of nontarget insects for host-specificity testing of
      candidate biocontrol agents of invasive wood-borers such as the Asian longhorned
      beetle, Anoplophora glabripennis (Motschulsky) (Coleoptera: Cerambycidae).
      Multifunnel and intercept traps, retrofitted to maintain live insects and baited
      with cerambycid-specific pheromone lures, were deployed in diverse forests in
      southeastern Massachusetts. We collected 1,288 adult beetles comprising 56
      species, mostly from the subfamilies targeted by the lures (Cerambycinae and
      Lamiinae). The type of trap and tree species in which the trap was hung did not
      seem to affect the species caught. Methods used to induce egg laying and
      techniques to rear cerambycid larvae are described. Dastarcus helophoroides
      (Fairmaire) (Coleoptera: Bothrideridae) is the most common Asian longhorned
      beetle parasitoid in China; therefore, we conducted tests to determine whether
      cerambycids native to North America would be at risk should this species be
      released. D. helophoroides attacked all six species tested: Monochamus
      scutellatus (Say) (Coleoptera: Cerambycidae: Lamiinae), Monochamus notatus
      (Drury) (Coleoptera: Cerambycidae: Lamiinae), Apriona rugicollis Chevrolat
      (Coleoptera: Cerambycidae: Lamiinae), Enaphalodes rufulus (Haldeman) (Coleoptera:
      Cerambycidae: Cerambycinae), Graphisurus fasciatus (DeGeer) (Coleoptera:
      Cerambycidae: Lamiinae), and Neoclytus acuminatus (F.) (Coleoptera: Cerambycidae:
      Cerambycinae). Parasitism of native cerambycids was not statistically different
      from parasitism of Asian longhorned beetle, except for N. acuminatus, which is a
      considerably smaller species than Asian longhorned beetle, and for M. notatus and
      M. scutellatus, which attack pine trees rather than hardwood trees like Asian
      longhorned beetle and the other native species tested. Our testing indicates that
      many native cerambycids would be vulnerable to D. helophoroides and we conclude
      that D. helophoroides should not be considered for release as a biocontrol agent
      in North America.

PMID- 30188984
TI  - Asleep blood pressure: a target for cardiovascular event reduction?

PMID- 30188985
TI  - Can genetics predict risk for sudden cardiac death? The relentless search for the
      Holy Grail.

PMID- 30188986
TI  - Glucocorticoid receptor isoforms and effects of glucocorticoids in ovulated mouse
      oocytes and preimplantation embryos.
AB  - To investigate possible involvement of glucocorticoid receptor (GR) in mediating
      effects of maternal stress or therapeutically administered glucocorticoids on
      early embryo we analyzed the expression of GR subtypes in ovulated mouse oocytes
      and preimplantation embryos. RT-PCR analysis results showed that GRalpha and
      GRgamma transcripts are relatively highly expressed in mouse oocytes, and both
      transcripts are present at lower amounts in preimplantation embryos. We also
      detected low expression of two other splice variants, GRbeta and a transcript
      orthologous to the human GR-P subtype, mainly at the blastocyst stage. Using
      Western blot analysis, we detected several GR protein bands that differed in size
      between oocytes and preimplantation embryos. To compare the effects of
      corticosterone (a major endogenous glucocorticoid in rodents) and dexamethasone
      (a synthetic glucocorticoid) on early embryos, we cultured mouse preimplantation
      embryos in the presence of these glucocorticoids. Corticosterone showed a strong
      inhibitory effect on embryo development (starting from a 50 MUM concentration),
      without a significant influence on apoptosis incidence. On the other hand,
      dexamethasone induced apoptosis in early embryo cells (starting from a 1.5 MUM
      concentration), and its effect on embryo development was less detrimental than
      that found with the same dose of corticosterone. In summary, our results showed
      that different GR subtypes are expressed in ovulated mouse oocytes and
      preimplantation embryos and that the composition of GR subtypes changes during
      early embryo development. Moreover, we found significant differences in the
      effects of the two glucocorticoids on early embryo development, which might be
      associated with activation of different GR subtypes.

PMID- 30188987
TI  - Sex, drugs, risk and resilience: analysis of data from the Canadian Health
      Behaviour in School-aged Children (HBSC) study.
AB  - Background: Risk-taking behaviour among adolescents, particularly those
      experiencing childhood adversities, can predispose to injury, unwanted pregnancy,
      long-term morbidity and death. Resilience, i.e. adapting to threats and thriving,
      has rarely been examined as a protective factor for adolescent risk-taking. We
      studied whether the malleable traits of empathy, confidence, self-control and
      optimism, all markers of resilience, align with decreased risk-taking despite
      adversity, among 11-15 year olds. Methods: From responses of 22 643 Canadian
      youth to the Health Behaviour in School-aged Children (2014) survey we validated
      a five-item resilience scale. Using regression analyses, this scale and a single
      measure of self-control were considered as potential protective factors for a
      composite measure of risk-taking behaviour and of initiation of sexual activity
      before age 14. Results: There was a dose-dependent association between greater
      resilience and diminished risk-taking for boys and, even more so, among girls.
      This relationship remained significant after controlling for family and social
      support, implying that greater resilience may override the detrimental impact of
      childhood adversity on risk-taking. The least resilient youth were most likely to
      report early sexual activity, although this relationship was not linear.
      Generally, the impact of self-control on risk-taking was not statistically
      significant, perhaps because of shortcomings of the self-control indicator.
      Conclusion: Brief screening protocols can identify assets that protect against
      risk-taking behaviours among adolescents. The malleable nature of these traits
      offers primary care providers and public health personnel a novel and effective
      route to decreasing adolescent risk-taking and fostering future health.

PMID- 30188988
TI  - Temperature-Dependent Development and Survival of Giant Whitefly Aleurodicus
      dugesii (Hemiptera: Aleyrodidae) Under Constant Temperatures.
AB  - The invasive giant whitefly Aleurodicus dugesii Cockerell (Hemiptera:
      Aleyrodidae) is a pest of over 300 plants species in the United States, many of
      which are economically important ornamentals and crops. Development and survival
      of A. dugesii was assessed at seven constant temperatures ranging from 10 to 35
      degrees C to provide a basis for phenological forecasting and assist in enhancing
      current biological control strategies. Complete development occurred from 15 to
      28 degrees C, with partial development occurring at 30 degrees C. Development
      time differed between sexes, with males developing 2 (at 25 degrees C) to 6 (at
      15 and 28 degrees C) d faster than females. Adult survival was highest at 25
      degrees C (65.4%), with survival rate declining rapidly at other temperatures.
      The relationship between temperature and development was evaluated using five
      nonlinear models (Lactin-2, Briere-1 and 2, Beta, and LRF). Additionally, the
      simple linear regression was used to calculate developmental degree-days (DDs).
      While all five nonlinear models evaluated fit the data well, the Briere-1 model
      provided the best fit of the data and estimated the optimal (25.3 degrees C),
      lower (9.9 degrees C), and upper (30.0 degrees C) developmental thresholds for
      male and female complete development. Using linear regression, DDs for complete
      development were calculated as 408 and 435 for males and females, respectively.
      The results of this study emphasize A. dugesii survival and development under
      varied temperature conditions.

PMID- 30188989
TI  - Morning Home Blood Pressure and Cardiovascular Events in a Japanese General
      Practice Population Over 80 Years Old: The J-HOP Study.
AB  - BACKGROUND: Home blood pressure (BP) measurement has been well accepted for use
      in the diagnosis and treatment of hypertension. However, data regarding the
      association between home BP levels and cardiovascular events in a general
      practice population aged >=80 years are sparse. METHODS: We analyzed the cases of
      349 patients >=80 years old from the Japan Morning Surge-Home Blood Pressure (J
      HOP) Study, a nationwide practice-based study of 4,310 Japanese with a history of
      and/or risk factors for cardiovascular disease. Home BP measurements were
      performed twice daily (morning and evening) over 14 consecutive days at baseline.
      RESULTS: During a median follow-up of 3.0 years, 32 composite cardiovascular
      events (13 strokes and 19 nonstroke events) occurred. Higher morning systolic BP
      (SBP) was a significant risk factor for composite cardiovascular events (hazard
      ratio (HR) per 10mm Hg, 1.23; 95% confidence interval (CI): 1.01-1.50) and stroke
      events (HR per 10mm Hg, 1.47; 95% CI: 1.08-2.00) after adjustment by the 4-year
      cardiovascular risk scores and clinic SBP. In the adjusted model, morning
      diastolic BP also tended to be a significant risk factor of stroke events (HR per
      5 mm Hg, 1.43; 95% CI: 1.00-2.05). However, these associations were not found for
      evening BP or clinic BP. CONCLUSIONS: Morning home BP showed a positive linear
      association with cardiovascular events, especially with stroke. This association
      was not observed for clinic BP or evening home BP. Based on these results, in
      very elderly Asian populations, measuring morning home BP might be important in
      clinical practice regardless of the individual's office BP level.

PMID- 30188990
TI  - Congenital Zika Syndrome and Extra-CNS detection of Zika virus in a pre-term
      newborn in Mexico.
AB  - Background: During pregnancy Zika virus (ZIKV) replicates in the placenta and
      central nervous system (CNS) of infected fetuses, nevertheless the ability of
      ZIKV to replicate in other fetal tissues has not been extensively characterized.
      Methods: We determined if dissemination outside the CNS of congenitally acquired
      ZIKV does exist by searching for the accumulation of the viral envelope protein
      (E), ZIKV RNA and infectious viral particles in different organs of a deceased
      newborn with Congenital Zika Syndrome (CZS). RT-qPCR was used to detect ZIKV RNA
      in the brain, thymus, lungs, kidneys, adrenal glands, spleen, liver and small
      intestine. The same tissues were analyzed by indirect immunofluorescence and
      immunoperoxidase assays using the monoclonal antibody 4G2 to detect ZIKV envelope
      antigen. Isolation of infectious ZIKV in cell culture was carried out using brain
      and kidney samples. Results: Post-mortem, virological analysis of multiple organs
      such as the kidneys (epithelial cells in the renal tubules), lungs (bronchial
      epithelia), thymus (epithelial cells inside the Hassall's corpuscles) and brain
      (neurons, ependymal cells and macrophages) revealed the presence of ZIKV RNA and
      envelope antigen. Other tissues of the deceased newborn tested positive by qPCR
      for EBV and HHV-6 such as the brain cortex (EBV) and the thymus, kidneys and
      adrenal glands (HHV-6). The kidneys were identified as a significant niche for
      viral replication given that infectious particles were successfully isolated from
      renal tissues. Conclusion: Our findings demonstrate the ability of congenitally
      acquired ZIKV to produce disseminated infections and the viral tropism towards
      epithelial cells.

PMID- 30188991
TI  - Effects of Multiple Forms of Information Bias on Estimated Prevalence of Suicide
      Attempts by Sexual Orientation: An Application of a Bayesian Misclassification
      Correction Method to Data from a Systematic Review.
AB  - Multiple epidemiologic studies demonstrate a disparity in suicide risk between
      sexual minority (lesbian, gay, bisexual) and heterosexual populations; however,
      both 'exposure' (sexual minority status) and outcome (suicide attempts) may be
      affected by information bias related to errors in self-reporting. We therefore
      applied a Bayesian misclassification correction method to account for possible
      information biases. A systematic literature search identified studies of lifetime
      suicide attempts in sexual minority and heterosexual adults, and frequentist meta
      analysis was used to generate unadjusted estimates of relative risk. A Bayesian
      model accounting for prior information about sensitivity and specificity of
      exposure and outcome measures was used to adjust for misclassification biases. In
      unadjusted frequentist analysis, the relative risk of lifetime suicide attempt
      comparing sexual minority to heterosexual groups was 3.38 (95% confidence
      interval: 2.65, 4.32). In Bayesian re-analysis, the estimated prevalence was
      slightly reduced in heterosexual adults and increased in sexual minority adults,
      yielding a relative risk of 4.67 (95% credible interval: 3.94, 5.73). The
      disparity in lifetime suicide attempts between sexual minority and heterosexual
      adults is greater than previously estimated, when accounting for multiple forms
      of information bias. Additional research on the impact of information bias in
      studies of sexual minority health should be pursued.

PMID- 30188992
TI  - Videoconferencing psychological therapy and anxiety: a systematic review.
AB  - Background: The growing worldwide prevalence of individuals with anxiety
      disorders has increased needs for mental health services. Due to limited number
      of mental health providers and community resources, especially in low-income
      countries, individuals often seek services from primary care settings. Through
      collaborative care models, services via telemedicine address the mental health
      provider shortage. While previous reviews show telemedicine effectively treats
      mental illness, a gap exists for reviews on videoconferencing psychological
      therapy for anxiety treatment. Objective: This systematic review aims to
      summarize videoconferencing psychological therapy for anxiety disorder treatment.
      Methods: Database searches were performed with PubMed, PsychINFO and Embase.
      Inclusion criteria identified controlled and uncontrolled studies evaluating
      videoconferencing psychological therapy. Studies were appraised using the
      Effective Public Health Practice Project Quality Assessment tool. Data collected
      included research design, sample size, intervention details, outcome results,
      intervention effect size and differences between videoconferencing psychological
      therapy and face-to-face therapy. Results: The search revealed 1253 articles,
      with 21 meeting inclusion criteria. Sample sizes ranged from 1 to 121
      participants; cognitive-behavioral therapy was most commonly evaluated.
      Participants' diagnoses included panic disorder with and without agoraphobia,
      generalized anxiety disorder, social anxiety disorder, social phobia and
      hypochondriasis. Three studies occurred in outpatient health care settings.
      Fourteen studies reported statistically significant improvement on anxiety
      measures; 11 reported clinically significant improvements. Effect sizes ranged
      from small to very large, and all controlled studies found no differences between
      videoconferencing and face-to face groups. Conclusion: Results provide promise
      for evidence-based interventions delivered via videoconferencing psychological
      therapy. More rigorous research is needed in various settings and populations.

PMID- 30188993
TI  - Averting the post-antibiotic era: successful use of meropenem/vaborbactam for
      carbapenem-resistant Serratia marcescens and Enterobacter aerogenes bacteraemia
      in a haemodialysis patient.

PMID- 30188994
TI  - Synergistic activity of an OmpA inhibitor and colistin against colistin-resistant
      Acinetobacter baumannii: mechanistic analysis and in vivo efficacy.
AB  - Objectives: Preventing bacterial contact with host cells can provide an
      additional approach to tackling MDR Acinetobacter baumannii. Recently, we
      identified AOA-2 as a potential blocker of A. baumannii outer membrane protein A
      without presenting bactericidal activity. Here, we aimed to study whether AOA-2
      can increase the activity of colistin against colistin-resistant A. baumannii in
      vitro and in vivo. Methods: Reference and clinical A. baumannii strains
      susceptible and resistant to colistin (CST-S and CST-R) were used. Microdilution
      and time-kill curve assays were performed to determine the synergy between AOA-2
      and colistin. SDS-PAGE assays with CST-S and CST-R outer membrane proteins and
      MALDI-TOF-TOF (MS-MS/MS) analysis were performed to determine the AOA-2 and
      colistin synergy mechanism. In a murine peritoneal sepsis model, the therapeutic
      efficacy of AOA-2 (10 mg/kg/24 h) in combination with a sub-optimal dose of
      colistin (10 mg/kg/24 h) against CST-R was evaluated by determining the bacterial
      load in tissues and blood, and mouse survival. Results: We showed that AOA-2
      increased the in vitro colistin susceptibility of reference and clinical CST-S
      and CST-R strains. This combination also enhanced their killing activity after 24
      h of drug exposure. This synergy is mediated by the overexpression of Omp25. In
      vivo, the combination of AOA-2 with colistin significantly reduced the bacterial
      load in tissues and blood, and increased mouse survival, compared with colistin
      monotherapy. Conclusions: We identified a novel class of antimicrobial agents
      that has proven to be effective in combination with colistin in an experimental
      model of severe infection by CST-R A. baumannii.

PMID- 30188995
TI  - The genome of a novel isolate of Prochlorococcus from the Red Sea contains
      transcribed genes for compatible solute biosynthesis.
AB  - Marine microbes possess genomic and physiological adaptations to cope with
      varying environmental conditions. So far, the effects of high salinity on the
      most abundant marine photoautotrophic organism, Prochlorococcus, in marine
      oligotrophic environments, are mostly unknown. Here, we report the isolation of a
      new Prochlorococcus strain (RSP50) belonging to high-light (HL) clade II from the
      Red Sea, one of the warmest and most saline bodies of water in the global oceans.
      A comparative genomic analysis identified a set of 59 genes that were exclusive
      to RSP50 relative to currently available Prochlorococcus genomes, the majority of
      which (70%) encode for hypothetical proteins of unknown function. However, three
      of the unique genes encode for a complete pathway for the biosynthesis of the
      compatible solute glucosylglycerol, and are homologous to enzymes found in the
      sister lineage Synechococcus. Metatranscriptomic analyses of this metabolic
      pathway in the water column of the Red Sea revealed that the corresponding genes
      were constitutively transcribed, independent of depth and light, suggesting that
      osmoregulation using glucosylglycerol is a general feature of HL II
      Prochlorococcus in the Red Sea.

PMID- 30188996
TI  - Is thymomectomy equivalent to complete thymectomy in non-myasthenic patients with
      early-stage thymoma?
AB  - A best evidence topic in thoracic surgery was written according to a structured
      protocol. The question addressed is whether thymomectomy can be equivalent to
      thymectomy for non-myasthenic early-stage thymoma in terms of recurrence and
      survival. Ten papers were chosen to answer the question. The authors, journal,
      date and country of publication, patient group studied, study type, relevant
      outcomes and results of these papers were tabulated. All studies included in this
      analysis are retrospective; most of them are small and from single-institution
      experiences, and only 3 used propensity-matched analysis to minimize the
      patients' selection bias. The choice of performing thymectomy or thymomectomy was
      based on surgeons' preference rather than on a standardized surgical approach.
      Most papers found that thymectomy was equivalent to thymomectomy in terms of
      outcomes, but these results could be affected by the intergroup differences in
      terms of follow-up length, administration of induction or adjuvant therapy,
      histological subtypes distribution and tumour size. Conversely, the studies of
      the Japanese Association for Research on the Thymus and the Chinese Alliance for
      Research in Thymoma found a higher rate of local recurrence in the thymomectomy
      group than in the thymectomy group. The National Comprehensive Cancer Network,
      National Cancer Institute and International Thymic Malignancy Interest Group
      recommend complete thymectomy in non-myasthenic patients with early thymoma;
      therefore, the identified studies in this review are not strong enough to change
      this recommendation.

PMID- 30188998
TI  - Using social norms theory for health promotion in low-income countries.

PMID- 30188997
TI  - The uncertain role of interpregnancy interval and why we need new approaches to
      an old problem.

PMID- 30188999
TI  - Stability and low induction propensity of cefiderocol against chromosomal AmpC
      beta-lactamases of Pseudomonas aeruginosa and Enterobacter cloacae.
AB  - Objectives: The siderophore cephalosporin cefiderocol possesses in vitro activity
      against MDR Gram-negative bacteria. The stability of cefiderocol against serine-
      and metallo-type carbapenemases has been reported previously, but little is known
      about how cefiderocol interacts with chromosomal AmpC beta-lactamases. We
      investigated a number of features of cefiderocol, namely antibacterial activity
      against AmpC overproducers, stability against AmpC beta-lactamases and propensity
      for AmpC induction using Pseudomonas aeruginosa and Enterobacter cloacae.
      Methods: MICs were determined by broth microdilution according to CLSI
      guidelines. The MIC of cefiderocol was determined in iron-depleted CAMHB.
      Hydrolysis of the antibiotics was determined by monitoring the changes in the
      absorbance in the presence of AmpC beta-lactamase, and AmpC induction was
      evaluated by double disc diffusion and nitrocefin degradation assays. Results:
      The MICs of ceftazidime and cefepime for PAO1 increased 4- to 16-fold with
      inactivation of either ampD or dacB, whereas cefiderocol MICs were little
      affected by these inactivations (<2-fold increase). Cefiderocol has 17- and 740
      fold lower affinity (higher Ki) to AmpCs of P. aeruginosa SR24-12 and E. cloacae
      P99, respectively, compared with ceftazidime. Both disc diffusion and nitrocefin
      degradation assays indicated that cefiderocol did not induce AmpC beta-lactamases
      of P. aeruginosa PAO1 and ATCC 27853 and E. cloacae ATCC 13047, whereas imipenem
      did. Conclusions: Cefiderocol showed in vitro activity against the AmpC
      overproducing strains, low affinity for chromosomal AmpC beta-lactamases, and a
      low propensity of temporal induction of AmpC beta-lactamases of P. aeruginosa and
      E. cloacae. These features relating to chromosomal AmpC could explain the potent
      antibacterial activity of cefiderocol against drug-resistant strains producing
      AmpC beta-lactamases.

PMID- 30189000
TI  - Engaging hospital patients in the medication reconciliation process using tablet
      computers.
AB  - Objective: Unintentional medication discrepancies contribute to preventable
      adverse drug events in patients. Patient engagement in medication safety beyond
      verbal participation in medication reconciliation is limited. We conducted a
      pilot study to determine whether patients' use of an electronic home medication
      review tool could improve medication safety during hospitalization. Materials and
      Methods: Patients were randomized to use a tool before or after hospital
      admission medication reconciliation to review and modify their home medication
      list. We assessed the quantity, potential severity, and potential harm of
      patients' and clinicians' medication changes. We also surveyed clinicians to
      assess the tool's usefulness. Results: Of 76 patients approached, 65 (86%)
      participated. Forty-eight (74%) made changes to their home medication list
      [before: 29 (81%), after: 19 (66%), p = .170]. Before group participants
      identified 57 changes that clinicians subsequently missed on admission medication
      reconciliation. Thirty-nine (74%) had a significant or greater potential
      severity, and 19 (36%) had a greater than 50-50 chance of harm. After group
      patients identified 68 additional changes to their reconciled medication lists.
      Fifty-one (75%) had a significant or greater potential severity, and 33 (49%) had
      a greater than 50-50 chance of harm. Clinicians reported believing that the tool
      would save time, and patients would supply useful information. Discussion: The
      results demonstrate a high willingness of patients to engage in medication
      reconciliation, and show that patients were able to identify important medication
      discrepancies and often changes that clinicians missed. Conclusion: Engaging
      patients in admission medication reconciliation using an electronic home
      medication review tool may improve medication safety during hospitalization.

PMID- 30189001
TI  - Intravenous Ketamine as an adjunct to procedural sedation during burn wound care
      and dressing changes.
AB  - Little has been published regarding intravenous (IV) ketamine for burn wound care
      in adult patients. Ketamine may serve as a safe alternative to provide conscious
      sedation and limit opioid administration to patients. The purpose of this study
      was to characterize IV ketamine use during burn wound care and establish its
      potential role as a safe adjunct to opioid and benzodiazepine medications. This
      is a retrospective review of adult patients admitted to a regional burn center
      who received IV ketamine for burn wound care. Patient demographics, medications,
      and ketamine-related side effects including hypertension and dysphoric reactions
      were recorded. Cardiopulmonary complications were also tracked. Thirty-six
      patients met inclusion criteria; 50 total cases were performed. The median
      patient age was 37 [IQR 28 - 55] years with a median burn size of 9.5 [IQR 4.0 -
      52] %TBSA. The median ketamine dose administered was 1.2 [IQR 0.8 - 2.1] mg/kg.
      IV midazolam was administered in almost all cases (98%) at a median dose of 3.0
      [IQR 2.0 - 5.0] mg. Opioids were administered in 13 of 50 cases (26%) at a median
      morphine equivalent dose of 10 [IQR 5.0 - 18] mg. In 46 cases (92%), patients
      denied unpleasant recall of medication. Dysphoric reactions were observed in 3
      cases (6%). Ketamine-induced hypertension occurred in 3 cases (6%) and all
      immediately responded to IV labetalol. There were no cardiopulmonary
      complications. These findings suggest IV ketamine provides a safe analgesia and
      sedative option for burn wound care. Given these findings, IV ketamine for burn
      wound care warrants further study.

PMID- 30189002
TI  - Effects of prophylactic antibiotics on patients with stable COPD: a systematic
      review and meta-analysis of randomized controlled trials.
AB  - Background: As bacterial infections provoke exacerbations, COPD patients may
      benefit from prophylactic antibiotics. However, evidence regarding their overall
      benefit-risk profile is conflicting. Objectives: To update previous evidence and
      systematically evaluate the beneficial effects and side effects of prophylactic
      antibiotics in stable COPD patients. Methods: Several databases were searched up
      to 26 April 2017 for randomized controlled trials (RCTs) on prophylactic
      antibiotics in stable COPD patients. The primary outcomes were exacerbations and
      quality of life. Duration and schedule of antibiotics were considered in subgroup
      analyses. Results: Twelve RCTs involving 3683 patients were included.
      Prophylactic antibiotics significantly reduced the frequency of exacerbations
      [risk ratio (RR) 0.74, 95% CI 0.60-0.92] and the number of patients with one or
      more exacerbations (RR 0.82, 95% CI 0.74-0.90). Erythromycin and azithromycin
      appeared the most effective, with the number needed to treat ranging from four to
      seven. Quality of life was also significantly improved by prophylactic
      antibiotics (mean difference -1.55, 95% CI -2.59 to -0.51). Time to first
      exacerbation was prolonged in six studies, with one conflicting result. Neither
      the rate of hospitalization nor the rate of adverse events was significantly
      changed. Furthermore, no significant changes were observed in lung function,
      bacterial load and airway inflammation. However, antibiotic-resistant isolates
      were significantly increased (OR 4.49, 95% CI 2.48-8.12). Conclusions:
      Prophylactic antibiotics were effective in preventing COPD exacerbations and
      improving quality of life among stable patients with moderate to severe COPD. The
      choice of prophylactic antibiotics should be analysed and considered case by
      case, especially for long and continuous use.

PMID- 30189004
TI  - Comment on: Applying definitions for multidrug resistance, extensive drug
      resistance and pandrug resistance to clinically significant livestock and
      companion animal bacterial pathogens.

PMID- 30189003
TI  - Improving asylum seekers' health awareness in a Hungarian refugee reception
      centre.
AB  - Due to its long border of the European Union Schengen Area, Hungary has long been
      affected by the rapidly growing inward migration towards the EU, which has become
      more acute in recent years. Inadequate access to healthcare among migrants has
      been widely reported and this may be due to a vast array of factors and may
      result in poorer health outcomes. Between August 2014 and April 2015 a
      questionnaire survey was conducted among migrants from a range of countries
      residing in the largest Hungarian refugee reception centre to establish
      participants' health knowledge and access to healthcare in Hungary (medical
      assessment, vaccination, etc.). The survey was complemented with an educational
      program which aimed to increase participants' awareness of healthcare provision
      and to promote the prevention of the infectious diseases that are common in
      Europe. The results showed that half the participants (52%) had no information of
      healthcare provision and the majority (61%) did not participate in any medical
      assessment since arriving in the reception centre. Since under-immunization may
      be a potential risk for the re-emergence of vaccine-preventable diseases for
      recipient countries, it was alarming that a significant proportion of African
      participants (21%) reported not having received any childhood vaccinations. Data
      demonstrated deficiencies in participants' health knowledge and also an urgent
      need to address mental health problems of arriving migrants. This article offers
      a valuable insight into the role of health educational interventions conducted
      for asylum seekers in refugee reception centres and discusses a number of
      practical application aspects for future educational programs.

PMID- 30189005
TI  - Pigmentation Diathesis of Hypertrophic Scar: An Examination of Known Signaling
      Pathways to Elucidate the Molecular Pathophysiology of Injury-Related Dyschromia.
AB  - Hypertrophic scar (HTS) occurs frequently after burn injury. Treatments for some
      aspects of scar morbidity exist, however, dyspigmentation treatments are lacking
      due to limited knowledge about why scars display dyschromic phenotypes. Full
      thickness wounds were created on duroc pigs that healed to form dyschromic HTS.
      HTS biopsies and primary cell cultures were then used to study pigmentation
      signaling. Biopsies of areas of both pigment types were taken for analysis. At
      the end of the experiment, melanocyte-keratinocyte co-cultures were established
      from areas of differential pigmentation. Heterogeneously dyspigmented scars
      formed with regions of hyperpigmentation and hypopigmentation. Melanocytes were
      present in both pigment types measured by S100beta qRT-PCR and immunostaining,
      and visualized by dendritic cell presence in primary cultures. P53 expression was
      not different between the two pigment types. Hyperpigmented scars had up
      regulated levels of POMC, ACTH, alpha-MSH, SCF, and c-KIT and MC1R receptors
      compared to hypopigmented regions. Many genes involved in dyspigmentation were
      differentially regulated by microarray analysis including MITF, TYR, TYRP1, and
      DCT. MiTF expression was not different upon further exploration, but TYR, TYRP1,
      and DCT were up regulated in intact biopsies measured by qRT-PCR and confirmed by
      immunostaining. This is the first work to confirm the presence of melanocytes in
      hypopigmented scar using qRT-PCR and primary cell culture. An understanding of
      the initial steps in dyspigmentation signaling, as well as the downstream effects
      of these signals, will inform treatment options for patients with scars and
      provide insight to where pharmacotherapy may be directed.

PMID- 30189006
TI  - Use of gentamicin-impregnated beads or sponges in the treatment of early acute
      periprosthetic joint infection: a propensity score analysis.
AB  - Objectives: Early acute periprosthetic joint infections (PJIs) treated with
      debridement, antibiotics and implant retention (DAIR) have failure rates ranging
      from 10% to 60%. We determined the efficacy of applying local gentamicin
      impregnated beads and/or sponges during debridement in early PJI. Methods:
      Patients with early acute PJI, defined as less than 21 days of symptoms and
      treated with DAIR within 90 days after index surgery, were retrospectively
      evaluated. Early failure was defined as PJI-related death, the need for implant
      removal or a second DAIR or antibiotic suppressive therapy owing to persistent
      signs of infection, all within 60 days after initial debridement. Overall failure
      was defined as implant removal at any timepoint during follow-up. A 1:1
      propensity score matching was performed to correct for confounding factors.
      Results: A total of 386 patients were included. Local gentamicin was applied in
      293 patients (75.9%) and was withheld in 93 patients (24.1%). Multivariate
      analysis demonstrated that the use of local gentamicin was independently
      associated with early failure (OR = 1.97, 95% CI = 1.12-3.48). After propensity
      matching, early failure was 40.3% in the gentamicin group versus 26.0% in the
      control group (P = 0.06) and overall failure was 5.2% in the gentamicin group
      versus 2.6% in the control group (P = 0.40). These numbers remained when solely
      analysing the application of gentamicin-impregnated sponges. Conclusions: Even
      after propensity score matching, failure rates remained higher if local
      gentamicin-impregnated beads and/or sponges were administered in early acute PJI.
      Based on these results, their use should be discouraged.

PMID- 30189007
TI  - Synergistic activation of CatSper Ca2+ channels in human sperm by oviductal
      ligands and endocrine disrupting chemicals.
AB  - STUDY QUESTION: Does the chemosensory activation of CatSper Ca2+ channels in
      human sperm give rise to additive, sub-additive or even synergistic actions among
      agonists? SUMMARY ANSWER: We show that oviductal ligands and endocrine disrupting
      chemicals (EDCs) activate human CatSper highly synergistically. WHAT IS KNOWN
      ALREADY: In human sperm, the sperm-specific CatSper channel controls the
      intracellular Ca2+ concentration and, thereby, several crucial stages toward
      fertilization. CatSper is activated by oviductal ligands and structurally diverse
      EDCs. The chemicals mimic the action of the physiological ligands, which might
      interfere with the precisely coordinated sequence of events underlying
      fertilization. STUDY DESIGN, SIZE, DURATION: For both oviductal ligands and EDCs,
      we examined in quantitative terms whether stimulation of human sperm in vitro
      with mixtures results in additive, sub-additive or synergistic actions.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: We studied activation of CatSper in
      sperm of healthy volunteers, using kinetic Ca2+ fluorimetry and patch-clamp
      recordings. The combined action of progesterone and prostaglandins and of the
      EDCs benzylidene camphor sulfonic acid (BCSA) and alpha-Zearalenol was evaluated
      by curve-shift analysis, curvilinear isobolographic analysis and the combination
      index method. MAIN RESULTS AND THE ROLE OF CHANCE: Analysis of the action of
      progesterone/prostaglandin and BCSA/alpha-Zearalenol mixtures in human sperm by
      fluorimetry revealed that the oviductal ligands and EDCs both evoke Ca2+ influx
      via CatSper in a highly synergistic fashion. Patch-clamp recordings of CatSper
      currents in human sperm corroborated the synergistic ligand-activation of the
      channel. LIMITATIONS, REASONS FOR CAUTION: This is an in vitro study. Future
      studies have to assess the physiological relevance in vivo. WIDER IMPLICATIONS OF
      THE FINDINGS: These findings indicate that the fertilization process is
      orchestrated by multiple oviductal CatSper agonists that act in concert to
      control the behavior of sperm. Moreover, our results substantiate the concerns
      regarding the negative impact of EDCs on male reproductive health. So far, safety
      thresholds like the "No Observed Adverse Effect Level (NOAEL)" or "No Observed
      Effect Concentration (NOEC)" are set for individual EDCs. Our finding that EDCs
      act synergistically in human sperm challenges the validity of this procedure.
      STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the German
      Research Foundation (SFB 645; CRU326), the Cells-in-Motion (CiM) Cluster of
      Excellence, Munster, (FF-2016-17), the 'Innovative Medical Research' of the
      University of Munster Medical School (BR121507), an EDMaRC research grant from
      the Kirsten and Freddy Johansen's Foundation, and the Innovation Fund Denmark
      (InnovationsFonden; 14-2013-4). The authors have no competing financial
      interests.

PMID- 30189008
TI  - Evaluation of the NG-Test CARBA 5 multiplex immunochromatographic assay for the
      detection of KPC, OXA-48-like, NDM, VIM and IMP carbapenemases.

PMID- 30189009
TI  - A Turning Point in Typhoid Control.

PMID- 30189010
TI  - Low schoolwork engagement and schoolwork difficulties predict smoking in
      adolescence?
AB  - Background: Low academic achievement has been associated with smoking but factors
      behind this association are poorly known. Such factors could include schoolwork
      disengagement and schoolwork difficulties. To assess the extent to which they
      contribute to the explanation of how health inequalities emerge, we study in a
      longitudinal design whether these have an independent effect on smoking or
      whether their effect is mediated through academic achievement. Methods:
      Longitudinal data were collected in the Helsinki metropolitan area, Finland in
      2011 and 2014. Participants were seventh-graders (12 - 13 years, N=9497). In the
      follow-up, 6534 students reported their smoking status in the ninth grade (15 -
      16 years). Smoking, schoolwork behavioural engagement, i.e. participation in
      academic activities, and disengagement, schoolwork difficulties and cognitive
      competence were self-reported by adolescents. Academic achievement was obtained
      from the Finnish national application register on upper secondary education. A
      mediation analysis was executed with bootstrapped confidence intervals. Results:
      Higher schoolwork behavioural engagement and cognitive competence in the seventh
      grade predicted that adolescents were more likely not to smoke in the ninth grade
      (all P<0.001) while higher schoolwork disengagement and schoolwork difficulties
      predicted adolescents' smoking (all P<0.001). The effects were mediated through
      academic achievement. Conclusions: Students' behavioural disengagement with
      schoolwork and schoolwork difficulties are risks for smoking initiation. Their
      effect is mediated through poor school achievement. As smoking often continues in
      adulthood and poor school performance typically leads to lower education,
      schoolwork disengagement and difficulties in adolescence constitute potential
      pathways to inequalities in health.

PMID- 30189011
TI  - Evaluation of the AusDiagnostics MT CRE EU assay for the detection of
      carbapenemase genes and transferable colistin resistance determinants mcr-1/-2 in
      MDR Gram-negative bacteria.
AB  - Objectives: To evaluate the AusDiagnostics MT CRE EU assay for the detection of
      carbapenemase and acquired colistin resistance genes in Gram-negative bacteria.
      Methods: The assay allows the detection of blaKPC, blaOXA-48-like, blaNDM,
      blaVIM, blaIMP, blaSIM, blaGIM, blaSPM, blaFRI, blaIMI, blaGES (differentiating
      ESBL and carbapenemase variants), blaSME and mcr-1/-2. It was evaluated against a
      panel of isolates including Enterobacteriaceae, Pseudomonas spp. and
      Acinetobacter spp. retrospectively (n = 210) and prospectively (n = 182).
      Results: The CRE EU assay was able to detect 268/268 carbapenemase genes, with
      239 belonging to the 'big five' families (KPC, OXA-48-like, NDM, VIM and IMP) and
      29 carbapenemase genes of the SIM, GIM, SPM, FRI, IMI, SME and GES families. It
      could distinguish between ESBL and carbapenemase variants of GES. It also allowed
      detection of mcr-1/-2 colistin resistance genes on their own or in isolates co
      producing a carbapenemase. Conclusions: The AusDiagnostics MT CRE EU assay
      offered wide coverage for detection of acquired carbapenemase genes. It required
      minimal hands-on time and delivered results in less than 4 h from bacterial
      culture.

PMID- 30189012
TI  - Pharmacokinetics of oxycodone/naloxone and its metabolites in patients with end
      stage renal disease during and between haemodialysis sessions.
AB  - Background: The pharmacokinetics of oxycodone in patients with end-stage renal
      disease (ESRD) requiring haemodialysis are largely unknown. Therefore, we
      investigated the pharmacokinetics of oxycodone/naloxone prolonged release and
      their metabolites in patients with ESRD during and between haemodialysis
      sessions. Methods: Single doses of oxycodone/naloxone (5/2.5 or 10/5 mg) were
      administered in nine patients with ESRD using a cross-over design on the day of
      dialysis and on a day between dialysis sessions. Plasma, dialysate and urine
      concentrations of oxycodone, naloxone and their metabolites were determined up to
      48 h post-dosing using a liquid chromatography-tandem mass spectrometry system.
      Results: Haemodialysis performed 6-10 h after dosing removed ~10% of the
      administered dose of oxycodone predominantly as unconjugated oxycodone and
      noroxycodone or conjugated oxymorphone and noroxymorphone. The haemodialysis
      clearance of oxycodone based on its recovery in dialysate was (mean +/- SD) 8.4
      +/- 2.1 L/h. The geometric mean (coefficient of variation) plasma elimination
      half-life of oxycodone during the 4-h haemodialysis period was 3.9 h (39%) which
      was significantly shorter than the 5.7 h (22%) without haemodialysis. Plasma
      levels of the active metabolite oxymorphone in its unconjugated form were very
      low. Conclusions: Oxycodone is removed during haemodialysis. The pharmacokinetics
      including the relatively short half-life of oxycodone in patients with ESRD with
      or without haemodialysis and the absence of unconjugated active metabolites
      indicate that oxycodone can be used at usual doses in patients requiring
      dialysis.

PMID- 30189013
TI  - Addressing Hand Hygiene Compliance in a Low-Resource Neonatal Intensive Care
      Unit: a Quality Improvement Project.
AB  - Objective: Our goal for this study was to quantify healthcare provider compliance
      with hand hygiene protocols and develop a conceptual framework for increasing
      hand hygiene compliance in a low-resource neonatal intensive care unit. Materials
      and Methods: We developed a 3-phase intervention that involved departmental
      discussion, audit, and follow-up action. A 4-month unobtrusive audit during night
      and day shifts was performed. The audit results were presented, and a conceptual
      framework of barriers to and solutions for increasing hand hygiene compliance was
      developed collectively. Results: A total of 1308 hand hygiene opportunities were
      observed. Among 1227 planned patient contacts, hand-washing events (707 [58.6%]),
      hand rub events (442 [36%]), and missed hand hygiene (78 [6.4%]) events were
      observed. The missed hand hygiene rate was 20% during resuscitation. Missed hand
      hygiene opportunities occurred 3.2 times (95% confidence interval, 1.9-5.3 times)
      more often during resuscitation procedures than during planned contact and 6.14
      times (95% confidence interval, 2.36-16.01 times) more often when providers moved
      between patients. Structural and process determinants of hand hygiene
      noncompliance were identified through a root-cause analysis in which all members
      of the neonatal intensive care unit team participated. The mean hand-washing
      duration was 40 seconds. In 83% of cases, drying hands after washing was
      neglected. Hand recontamination after hand-washing was seen in 77% of the cases.
      Washing up to elbow level was observed in 27% of hand-wash events. After
      departmental review of the study results, hand rubs were placed at each bassinet
      to address these missed opportunities. Conclusions: Hand hygiene was suboptimal
      during resuscitation procedures and between patient contacts. We developed a
      conceptual framework for improving hand hygiene through a root-cause analysis.

PMID- 30189014
TI  - The changing landscape of vancomycin-resistant Enterococcus faecium in Australia:
      a population-level genomic study.
AB  - Background: Vancomycin-resistant Enterococcus faecium (VREfm) represent a major
      source of nosocomial infection worldwide. In Australia, there has been a recent
      concerning increase in bacteraemia associated with the vanA genotype, prompting
      investigation into the genomic epidemiology of VREfm. Methods: A population-level
      study of VREfm (10 November-9 December 2015) was conducted. A total of 321 VREfm
      isolates (from 286 patients) across Victoria State were collected and sequenced
      with Illumina NextSeq. SNPs were used to assess relatedness. STs and genes
      associated with resistance and virulence were identified. The vanA-harbouring
      plasmid from an isolate from each ST was assembled using long-read data. Illumina
      reads from remaining isolates were then mapped to these assemblies to identify
      their probable vanA-harbouring plasmid. Results: vanA-VREfm comprised 17.8% of
      isolates. ST203, ST80 and a pstS(-) clade, ST1421, predominated (30.5%, 30.5% and
      37.2%, respectively). Most vanB-VREfm were ST796 (77.7%). vanA-VREfm were more
      closely related within hospitals versus between them [core SNPs 10 (IQR 1-357)
      versus 356 (179-416), respectively], suggesting discrete introductions of vanA
      VREfm, with subsequent intra-hospital transmission. In contrast, vanB-VREfm had
      similar core SNP distributions within versus between hospitals, due to widespread
      dissemination of ST796. Different vanA-harbouring plasmids were found across STs.
      With the exception of ST78 and ST796, Tn1546 transposons also varied.
      Phylogenetic analysis revealed Australian strains were often interspersed with
      those from other countries, suggesting ongoing cross-continental transmission.
      Conclusions: Emerging vanA-VREfm in Australia is polyclonal, indicating repeat
      introductions of vanA-VREfm into hospitals and subsequent dissemination. The
      close relationship to global strains reinforces the need for ongoing screening
      and control of VREfm in Australia and abroad.

PMID- 30189015
TI  - Extending (Q)SARs to incorporate proprietary knowledge for regulatory purposes:
      is aromatic N-oxide a structural alert for predicting DNA-reactive mutagenicity?
AB  - (Quantitative) structure-activity relationship or (Q)SAR predictions of DNA
      reactive mutagenicity are important to support both the design of new chemicals
      and the assessment of impurities, degradants, metabolites, extractables and
      leachables, as well as existing chemicals. Aromatic N-oxides represent a class of
      compounds that are often considered alerting for mutagenicity yet the scientific
      rationale of this structural alert is not clear and has been questioned. Because
      aromatic N-oxide-containing compounds may be encountered as impurities,
      degradants and metabolites, it is important to accurately predict mutagenicity of
      this chemical class. This article analysed a series of publicly available
      aromatic N-oxide data in search of supporting information. The article also used
      a previously developed structure-activity relationship (SAR) fingerprint
      methodology where a series of aromatic N-oxide substructures was generated and
      matched against public and proprietary databases, including pharmaceutical data.
      An assessment of the number of mutagenic and non-mutagenic compounds matching
      each substructure across all sources was used to understand whether the general
      class or any specific subclasses appear to lead to mutagenicity. This analysis
      resulted in a downgrade of the general aromatic N-oxide alert. However, it was
      determined there were enough public and proprietary data to assign the quindioxin
      and related chemicals as well as benzo[c][1,2,5]oxadiazole 1-oxide subclasses as
      alerts. The overall results of this analysis were incorporated into Leadscope's
      expert-rule-based model to enhance its predictive accuracy.

PMID- 30189016
TI  - Diode-pumped neodymium:yttrium aluminum garnet laser effects on the visceral
      pleura in an ex vivo porcine lung model.
AB  - OBJECTIVES: Resection of tumour spread on a very thin visceral pleura might be
      challenging, and collateral damage to the lung parenchyma might occur. We aimed
      to develop an operative technique, which might facilitate the parenchyma-sparing
      destruction of the visceral pleura. This experimental work investigated the
      effects of a neodymium:yttrium aluminum garnet (Nd:YAG) laser on the visceral
      pleura in an ex vivo porcine lung model. METHODS: We used a diode-pumped Nd:YAG
      laser (Limax(r) 120, KLS Martin, Tuttlingen, Germany) to investigate the effects
      on the visceral pleural in 20 porcine lungs. The laser was applied on a
      standardized length in 4 different settings: Group I (80 W, 6 s), Group II (80 W,
      12 s), Group III (120 W, 6 s) and Group IV (120 W, 12 s). All specimens were
      analysed histologically. RESULTS: The mean thickness of the visceral pleura was
      81 +/- 10 MUm. Increasing power levels and longer application duration resulted
      in significantly enhanced laser destruction effects. The mean depths of the
      carbonization zone were 142 +/- 42 um, 378 +/- 137 um, 607 +/- 155 um and 1371 +/
      271 MUm for Groups I-IV, respectively (P < 0.001). The ratio of carbonization
      zone to pleural thickness was measured for each section (C/P ratio) to quantify
      the thermal effects. The corresponding C/P ratio for Groups I-IV were 1.72 +/-
      0.55, 4.98 +/- 1.96, 7.11 +/- 1.61 and 17.35 +/- 4.35, respectively (P < 0.001).
      CONCLUSIONS: Our study showed that increasing power levels and application
      duration of the laser lead to a significantly increased carbonization and
      destruction zones. Further in vivo human studies should evaluate the feasibility
      of laser application for a potential translational relevance for human use.

PMID- 30189017
TI  - Overexpression of Grainyhead-like 3 causes spina bifida and interacts genetically
      with mutant alleles of Grhl2 and Vangl2 in mice.
AB  - The genetic basis of human neural tube defects (NTDs), such as anencephaly and
      spina bifida (SB), is complex and heterogeneous. Grainyhead-like genes represent
      candidates for involvement in NTDs based on the presence of SB and exencephaly in
      mice carrying loss-of-function alleles of Grhl2 or Grhl3. We found that
      reinstatement of Grhl3 expression, by bacterial artificial chromosome (BAC)
      mediated transgenesis, prevents SB in Grhl3-null embryos, as in the Grhl3
      hypomorphic curly tail strain. Notably, however, further increase in expression
      of Grhl3 causes highly penetrant SB. Grhl3 overexpression recapitulates the
      spinal NTD phenotype of loss-of-function embryos, although the underlying
      mechanism differs. However, it does not phenocopy other defects of Grhl3-null
      embryos such as abnormal axial curvature, cranial NTDs (exencephaly) or skin
      barrier defects, the latter being rescued by the Grhl3-transgene. Grhl2 and Grhl3
      can form homodimers and heterodimers, suggesting a possible model in which
      defects arising from overexpression of Grhl3 result from sequestration of Grhl2
      in heterodimers, mimicking Grhl2 loss of function. This hypothesis predicts that
      increased abundance of Grhl2 would have an ameliorating effect in Grhl3
      overexpressing embryo. Instead, we observed a striking additive genetic
      interaction between Grhl2 and Grhl3 gain-of-function alleles. Severe SB arose in
      embryos in which both genes were expressed at moderately elevated levels that
      individually do not cause NTDs. Furthermore, moderate Grhl3 overexpression also
      interacted with the Vangl2Lp allele to cause SB, demonstrating genetic
      interaction with the planar cell polarity signalling pathway that is implicated
      in mouse and human NTDs.

PMID- 30189019
TI  - The effects of methotrexate and hydroxychloroquine combination therapy vs
      methotrexate monotherapy in early rheumatoid arthritis patients.
AB  - Objectives: To investigate the added value of MTX-HCQ combination therapy (CTG)
      in early RA in a controlled cohort study. MTX monotherapy (MTG) is recommended as
      (part of) first choice treatment but no head-to-head comparisons are available
      comparing MTX-HCQ CTG with MTG. Methods: RA patients from the Sint
      Maartenskliniek and Radboudumc Nijmegen who started MTX with or without
      concomitant HCQ from April 2010 to October 2015 were included. The primary
      outcome was the between-group DeltaDAS28-CRP at 6 months, and secondary outcomes
      were DeltaDAS28-CRP at 12 months, EULAR response at 6 and 12 months, and
      treatment intensification. Regression modelling was used to correct for
      confounding. Results: We included 325 patients, with only small between-group
      differences at baseline. The DAS28-CRP improvement at 6 months was larger in the
      CTG (Delta = 0.38 (CI: 0.01, 0.76)), and the difference between groups in DAS28
      CRP improvement was smaller at 12 months (Delta = 0.22 points (CI:-0.19, -0.62)).
      At 6 months, a higher percentage of patients had a good EULAR response in the CTG
      (Delta = 15% (CI: 2.7%, 27%)). This difference was reduced at 12 months (Delta =
      6% (CI -6.4%, 19%)). Treatment intensification with conventional synthetic DMARDs
      was more likely in the MTG (Delta = 31% (CI: -43%, 19%)). The proportion of
      patients starting biologic DMARD treatment during the observation period was
      comparable (Delta = 2% (CI: -8%, 12%)). Discussion: In contrast to indirect
      comparison review data, MTX-HCQ seems somewhat more effective after 6 months than
      MTX monotherapy in early RA patients. After 12 months, we observed no significant
      differences between the two strategies, probably due to treat-to-target efforts.

PMID- 30189018
TI  - Repeat Stereotactic Radiosurgery for Progressive or Recurrent Vestibular
      Schwannomas.
AB  - BACKGROUND: Stereotactic radiosurgery (SRS) is a highly effective management
      approach for patients with vestibular schwannomas (VS), with 10-yr control rates
      up 98%. When it fails, however, few data are available to guide management.
      OBJECTIVE: To perform a retrospective analysis of patients who underwent 2 SRS
      procedures on the same VS to assess the safety and efficacy of this practice.
      METHODS: This study was opened to centers of the International Gamma Knife
      Research Foundation (IGKRF). Data collected included patient characteristics,
      clinical symptoms at the time of SRS, radiosurgery dosimetric data, imaging
      response, clinical evolution, and survival. Actuarial analyses of tumor responses
      were performed. RESULTS: Seventy-six patients from 8 IGKRF centers were
      identified. Median follow-up from the second SRS was 51.7 mo. Progression after
      the first SRS occurred at a median of 43 mo. Repeat SRS was performed using a
      median dose of 12 Gy. Actuarial tumor control rates at 2, 5, and 10 yr following
      the second SRS were 98.6%, 92.2%, and 92.2%, respectively. Useful hearing was
      present in 30%, 8%, and 5% of patients at first SRS, second SRS, and last follow
      up, respectively. Seventy-five percent of patients reported stable or improved
      symptoms following the second SRS. Worsening of facial nerve function
      attributable to SRS occurred in 7% of cases. There were no reports of
      radionecrosis, radiation-associated edema requiring corticosteroids, radiation
      related neoplasia, or death attributable to the repeat SRS procedure. CONCLUSION:
      Patients with progressing VS after radiosurgery can be safely and effectively
      managed using a second SRS procedure.

PMID- 30189020
TI  - Isolated intracranial arterial hypertension.

PMID- 30189021
TI  - EXPOSURE OF A SERVICE TECHNICIAN REPAIRING A BIPLANE X-RAY SYSTEM.
AB  - While repairing a biplane cardiovascular X-ray system in a hospital, a service
      technician accidentally activated the system's floor pedal. He continued his work
      under unnoticed exposure for about 5 min until the system alarm was automatically
      activated. About 2 h after the exposure, the technician developed an erythema on
      parts of his left face and neck. The next day, he reported his incident to the
      competent authorities and was hospitalised in a unit specialised in treating
      heavily irradiated patients. Frequent blood analysis did not show any signs for a
      significant exposure to radiation. The Federal Office of Public Health then
      conducted extensive dose estimations. It could be shown that the dismounted
      collimator was always in front of the lateral X-ray tube, shielding the
      technician from the direct beam. The dose estimations came to the following
      conservative results: an effective dose of 5 mSv, a skin dose of 200 mSv, an eye
      lens dose of 100 mSv and an extremity dose (arm) of 700 mSv. The cause of the
      erythema remains unclear since the estimated doses are thought to be too low to
      induce any visible effect on the skin.

PMID- 30189022
TI  - Commentary: The Zurich Checklist for Safety in the Intraoperative Magnetic
      Resonance Imaging Suite: Technical Note.

PMID- 30189023
TI  - Commentary: Utility of Preoperative Simulation for Ventricular Catheter Placement
      via a Parietooccipital Approach in Normal-Pressure Hydrocephalus.

PMID- 30189024
TI  - Supratotal Resection of Residual Clival Chordoma With Combined Endoscopic
      Endonasal and Contralateral Transmaxillary Approaches: 2-Dimensional Operative
      Video.
AB  - The optimal treatment for skull base chordomas is gross total resection followed
      by radiotherapy and not radiation of partially resected tumors. Supratotal
      resection, defined as removal beyond all involved bone and dura, is ideal but
      difficult to achieve. In this video, we present the case of a 37-yr-old man with
      new onset of progressive cranial nerve sixth palsy and a skull base lesion
      compatible with clival chordoma. He underwent partial surgical resection at an
      outside institution via transcranial approach, with significant tumor residual at
      the clivus, dorsum sella, posterior clinoids, and petrous apex, extensive dural
      invasion, and intradural extension with attachment to the basilar artery and its
      long perforating branches. Supratotal surgical resection was achieved using an
      endoscopic endonasal transclival approach, ipsilateral transpteryoid approach to
      the foramen lacerum for carotid artery mobilization, bilateral interdural
      transcavernous approach with posterior clinoidectomies, and con-tralateral
      transmaxillary approach to the petrous apex. Reconstruction was performed in a
      multilayer fashion with fascia lata and fat grafts, extended nasoseptal flap, a
      lumbar drainage for 3 d. No cerebrospinal fluid leak occurred, and the abducens
      nerve palsy significantly improved at 3-mo follow-up. Proton therapy is planned.
      Recent advances in endoscopic endonasal surgery allow for very high rates of
      complete and even supratotal resection despite the challenging location. A long
      learning curve to acquire the technical skills and complex surgical anatomy is
      required to decrease complication rates and achieve maximal resection in
      chordomas. Reoperations are more challenging and risky; therefore, first attempt
      should have curative intent. The patient signed informed consent including the
      use of photographic and video material for educational or academic purposes.

PMID- 30189025
TI  - The course and predictors of perceived unsupportive responses by family and
      friends among women newly diagnosed with gynecological cancers.
AB  - Perceived unsupportive responses from close others play an important role in
      psychological adaptation of patients with cancer. Little is known about whether
      these negative responses change after someone experiences a serious life event,
      and even less is known about the individual characteristics and related factors
      that might contribute to both the levels of and changes in perceived unsupportive
      responses over the course of adaptation to an experience. This longitudinal study
      aimed to evaluate changes in perceived unsupportive behavior from family and
      friends among women newly with gynecologic cancer as well as initial demographic,
      disease, and psychological factors that predict the course of perceived
      unsupportive behavior over time. Women (N = 125) assigned to the usual care arm
      of a randomized clinical trial comparing a coping and communication intervention
      with a supportive counseling intervention to usual care completed six surveys
      over an 18 month period. Growth models using multilevel modeling were used to
      predict unsupportive responses over time. Average levels of perceived
      unsupportive responses from family and friends were low. Unsupportive responses
      varied from patient to patient, but patients did not report a systematic change
      in perceived unsupportive responses over time. Cultivating meaning and peace and
      coping efficacy were associated with fewer perceived unsupportive responses as
      well as reductions in perceived unsupportive responses over time. Emotional
      distress, cancer concerns, functional impairment, holding back sharing concerns,
      and cognitive and behavioral avoidance predicted higher perceived unsupportive
      responses over time. The findings are discussed in terms of the self-presentation
      theory and social network responses to persons undergoing difficult life events.

PMID- 30189026
TI  - High-serum phosphate and parathyroid hormone distinctly regulate bone loss and
      vascular calcification in experimental chronic kidney disease.
AB  - Background: In chronic kidney disease (CKD), increases in serum phosphate and
      parathyroid hormone (PTH) aggravate vascular calcification (VC) and bone loss.
      This study was designed to discriminate high phosphorus (HP) and PTH contribution
      to VC and bone loss. Methods: Nephrectomized rats fed a HP diet underwent either
      sham operation or parathyroidectomy and PTH 1-34 supplementation to normalize
      serum PTH. Results: In uraemic rats fed a HP diet, parathyroidectomy with serum
      PTH 1-34 supplementation resulted in (i) reduced aortic calcium (80%) by
      attenuating osteogenic differentiation (higher alpha-actin; reduced Runx2 and
      BMP2) and increasing the Wnt inhibitor Sclerostin, despite a similar degree of
      hyperphosphataemia, renal damage and serum Klotho; (ii) prevention of bone loss
      mostly by attenuating bone resorption and increases in Wnt inhibitors; and (iii)
      a 70% decrease in serum calcitriol levels despite significantly reduced serum
      Fgf23, calcium and renal 24-hydroxylase, which questions that Fgf23 is the main
      regulator of renal calcitriol production. Significantly, when vascular smooth
      muscle cells (VSMCs) were exposed exclusively to high phosphate and calcium, high
      PTH enhanced while low PTH attenuated calcium deposition through parathyroid
      hormone 1 receptor (PTH1R) signalling. Conclusions: In hyperphosphataemic CKD, a
      defective suppression of high PTH exacerbates HP-mediated osteogenic VSMC
      differentiation and reduces vascular levels of anti-calcifying sclerostin.

PMID- 30189027
TI  - Rational optimization of a monoclonal antibody for simultaneous improvements in
      its solution properties and biological activity.
AB  - Developability considerations should be integrated with lead engineering of
      antibody drug candidates in interest of their cost effective translations into
      medicines. To explore feasibility of this imperative, we have performed rational
      mutagenesis studies on a monoclonal antibody (MAB1) whose development was
      discontinued owing to manufacturability hurdles. Seven computationally designed
      variants of MAB1 containing single point (V44K, E59S, E59T and E59Y) and double
      (V44KE59S, V44KE59T and V44KE59Y) mutations in its light chain were produced in
      Chinese Hamster Ovary (CHO) cells and purified by using platform processes
      employed during commercial scale production of monoclonal antibodies. MAB1 and
      its variants were formulated in the same platform buffer and subjected to a
      battery of experiments to assess their solution behaviors, and biological
      activities. Five of the seven (71%) variants of MAB1 demonstrated improved
      biophysical attributes in multiple experimental testings. Contrary to the
      commonly expressed reservations about potential biological activity loss upon
      developability optimizations, the improvements in solution behavior of MAB1 also
      increased its biological activity up to ~180%. In particular, concentrate-ability
      and apparent solubility of V44KE59S improved to ~150% and ~160%, respectively.
      Its diffusion interaction parameter (kD) reduced to 28% and viscosity at ~100
      mg/ml decreased to less than half of the corresponding values for MAB1. V44KE59S
      is also slightly more active and its transfections in CHO cells were more
      productive. It also degraded slower than MAB1 in three month long 25 degrees C
      and 40 degrees C formulation stability studies. These results open doors to an
      exciting realm of structure-based biologic drug design where developability and
      biological activity can be simultaneously optimized at the molecular engineering
      stages.

PMID- 30189028
TI  - Three-dimensional simulation for left ventricular assist device implantation in a
      small patient with chest wall deformity.
AB  - The rate of patients requiring left ventricular assist device (LVAD) implantation
      remains at a pace exceeding 2000 per year worldwide. Children and small adult
      patients, with a body surface area <1.5 m2, are at a disadvantage for receiving
      an implantable LVAD because of its large pump size. Preoperative simulation of
      the results of various LVAD implantation methods and devices in such challenging
      cases will be helpful for surgeons. Herein, we introduce a preoperative LVAD
      simulation method using image processing software and present a case in which we
      obtained satisfactory results.

PMID- 30189029
TI  - Respiratory Pathogens in Children 1 Month to 5 Years of Age Presenting With
      Undifferentiated Acute Respiratory Distress in 2 District-Level Hospitals in
      Ghana.
AB  - Ghanaian children (2176) aged <5 years who presented with undifferentiated acute
      respiratory distress were tested for respiratory pathogens using a BioFire
      FilmArray polymerase chain reaction assay. Rhinovirus and/or enterovirus was
      detected in 36% of the assays, respiratory syncytial virus in 11%, and
      parainfluenza in 7%. Respiratory syncytial virus and metapneumovirus were
      detected more frequently in the rainy season than in the dry season.

PMID- 30189030
TI  - Thoracolumbar Injury Classification and Severity Score in Children: A Validity
      Study.
AB  - BACKGROUND: The Thoracolumbar Injury Classification and Severity Score (TLICS)
      has been shown to be a valid tool for assessing the need for surgical
      intervention in adult patients. There is limited insight into its usefulness in
      children. OBJECTIVE: To assess the validity of the TLICS system in pediatric
      patients. METHODS: The medical records for pediatric patients with acute,
      traumatic thoracolumbar fractures at two Level 1 trauma centers were reviewed
      retrospectively. A TLICS score was calculated for each patient using computed
      tomography and magnetic resonance images, along with the neurological examination
      recorded in the patient's medical record. TLICS scores were compared with the
      type of treatment received. Receiver operating characteristic (ROC) curve
      analysis was employed to quantify the validity of the TLICS scoring system.
      RESULTS: TLICS calculations were completed for 165 patients. The mean TLICS score
      was 2.9 (standard deviation +/- 2.7). Surgery was the treatment of choice for 23%
      of patients. There was statistically significant agreement between the TLICS
      suggested treatment and the actual treatment received (P < 0.001). The ROC curve
      calculated using multivariate logistic regression analysis of the TLICS system's
      parameters as a tool for predicting treatment demonstrated excellent
      discriminative ability, with an area under the ROC curve of 0.96, which was also
      statistically significant (P < 0.001). CONCLUSION: The TLICS system demonstrates
      good validity for selecting appropriate thoracolumbar fracture treatment in
      pediatric patients.

PMID- 30189031
TI  - Accuracy and Safety of Lateral Vertebral Notch-Referred Technique Used in
      Subaxial Cervical Pedicle Screw Placement.
AB  - BACKGROUND: Biomechanical studies revealed that pedicle screw instrumentation has
      a superior stabilizing effect compared with other internal fixations in
      reconstructing the subaxial cervical spine. However, severe neurovascular risks
      preclude surgeons from routinely conducting pedicle screw manipulation in
      cervical spine. OBJECTIVE: To evaluate the accuracy and safety of the lateral
      vertebral notch (LVN)-referred technique used in subaxial cervical pedicle screw
      (CPS) placement. METHODS: One hundred thirty-five consecutive retrospective
      patients with cervical disorders underwent the LVN-referred technique for CPS
      placements in 3 spine centers. Postoperative pedicle perforations were confirmed
      by CT scans to assess the technical accuracy. Neurovascular complications derived
      from CPS misplacements were recorded to evaluate the technical safety. RESULTS: A
      total of 718 CPSs were inserted into subaxial cervical spine. Postoperative CT
      scans revealed that the accuracy of CPS placement was superior. Neither vertebral
      artery injury nor spinal cord injury occurred. One radiculopathy was from a
      unilateral C6 nerve root compression. A screw-related neurovascular injury rate
      of 0.7% occurred in this cohort. Additionally, there was no significant
      difference in the accuracy of CPS placement among 3 surgeons (H = 1.460, P =
      .482). The relative standard deviation values revealed that technical
      reproducibility was acceptable. Furthermore, there was no significant difference
      between the patients' pedicle transverse angles and inserted CPS transverse
      angles from C3 to C7 (all P > .05). CONCLUSION: The LVN is a reliable and
      consistent anatomic landmark for CPS placement. The accuracy and safety of
      subaxial CPS placement by using LVN-referred technique are highly acceptable,
      which may endow this technique to be practicably performed in selected patients.

PMID- 30189032
TI  - Power, false discovery rate and Winner's Curse in eQTL studies.
AB  - Investigation of the genetic architecture of gene expression traits has aided
      interpretation of disease and trait-associated genetic variants; however, key
      aspects of expression quantitative trait loci (eQTL) study design and analysis
      remain understudied. We used extensive, empirically driven simulations to explore
      eQTL study design and the performance of various analysis strategies. Across
      multiple testing correction methods, false discoveries of genes with eQTLs
      (eGenes) were substantially inflated when false discovery rate (FDR) control was
      applied to all tests and only appropriately controlled using hierarchical
      procedures. All multiple testing correction procedures had low power and inflated
      FDR for eGenes whose causal SNPs had small allele frequencies using small sample
      sizes (e.g. frequency <10% in 100 samples), indicating that even moderately low
      frequency eQTL SNPs (eSNPs) in these studies are enriched for false discoveries.
      In scenarios with >=80% power, the top eSNP was the true simulated eSNP 90% of
      the time, but substantially less frequently for very common eSNPs (minor allele
      frequencies >25%). Overestimation of eQTL effect sizes, so-called 'Winner's
      Curse', was common in low and moderate power settings. To address this, we
      developed a bootstrap method (BootstrapQTL) that led to more accurate effect size
      estimation. These insights provide a foundation for future eQTL studies,
      especially those with sampling constraints and subtly different conditions.

PMID- 30189033
TI  - Disney Trap Attractiveness for the Cortelezzii Series (Diptera: Psychodidae,
      Phlebotominae) in a Fishing Tourism Area, Bonito Municipality, Mato Grosso do Sul
      State, Brazil.
AB  - Sand fly fauna is frequently sampled using automatic light or Shannon traps, yet
      few studies have been devoted to investigating the effectiveness of Disney traps
      baited with live animals as an attractant. This study sought to identify the
      phlebotomine fauna attracted to Disney traps having hamsters (Mesocricetus
      auratus) as bait. A hamster-baited Disney trap was installed in a gallery forest
      located in Aguas do Miranda District, Bonito Municipality, Mato Grosso do Sul
      state, Brazil, from November 2011 to October 2012. A total of 717 phlebotomines
      were collected, in which male (251) and female (463) specimens of the Cortelezzii
      series (Diptera: Psychodidae) predominated (99%). Males were attracted from
      January to July, whereas the females were predominantly attracted from January to
      May. No significant correlation was observed between the monthly climatic
      averages of temperature, rains and humidity, and the numbers of insects
      collected. Although these findings showed the attractiveness of both sexes of the
      species of the Cortelezzii series to golden hamsters, further studies are needed
      to investigate the blood meal preferences of these females to other rodents. As
      rodents have been reported as reservoirs of Leishmania spp. (Kinetoplastida:
      Trypanosomatidae), research using live-baited traps can reveal feeding
      preferences of sand flies and the importance of various rodent species in the
      zoonotic cycle.

PMID- 30189034
TI  - Morphometric and genetic variation in 8 breeds of Ethiopian camels (Camelus
      dromedarius).
AB  - Dromedary camels (Camelus dromedarius) are a domesticated and closely guarded
      economic staple of indigenous people located throughout Ethiopian territorial
      states. Seventeen morphometric variables were examined to determine intraspecific
      variation among 8 pastoralist-designated breeds of camels. Additionally, DNA
      sequences from mitochondrial cytochrome-b gene and genotyping of 6 nuclear
      microsatellite loci were examined to assess genetic diversity and phylogenetic
      relationship of Ethiopian camels. Examination of 525 individuals revealed
      significant morphometric differentiation in Afar as compared with the remaining 7
      breeds. Analysis of cytochrome-b sequences failed to recover monophyletic groups
      associated with pastoralist-recognized breeds. Analysis of 6 microsatellite loci
      from 104 individuals depicted no resolution of distinct genetic lineages in
      accordance to geographical or designated breeds. Overall, separation of 2
      ecotypes based on the morphometric data was supported; however, genetic analysis
      of cytochrome-b and microsatellite data failed to support any unique genetic
      lineage or statistically significant population structure.

PMID- 30189036
TI  - Moral Enhancement Can Kill.
AB  - There is recent empirical evidence that personal identity is constituted by one's
      moral traits. If true, this poses a problem for those who advocate for moral
      enhancement, or the manipulation of a person's moral traits through
      pharmaceutical or other biological means. Specifically, if moral enhancement
      manipulates a person's moral traits, and those moral traits constitute personal
      identity, then it is possible that moral enhancement could alter a person's
      identity. I go a step further and argue that under the right conditions, moral
      enhancement can kill the subject of the enhancement. I then argue that these
      conditions are not remote.

PMID- 30189035
TI  - MGMT promoter methylation status testing to guide therapy for glioblastoma:
      refining the approach based on emerging evidence and current challenges.
AB  - Glioblastoma (GBM) is the most common primary malignant brain tumor, with a
      universally poor prognosis. The emergence of molecular biomarkers has had a
      significant impact on histological typing and diagnosis, as well as predicting
      patient survival and response to treatment. The methylation status of the O6
      methylguanine-DNA methyl-transferase (MGMT) gene promoter is one such molecular
      biomarker. Despite the strong evidence supporting the role of MGMT methylation
      status in prognostication, its routine implementation in clinical practice has
      been challenging. The methods and optimal cutoff definitions for MGMT status
      determination remain controversial. Variation in detection methods between
      laboratories presents a major challenge for consensus. Moreover, consideration of
      other clinical and genetic/epigenetic factors must also be incorporated into
      treatment decision making. In this review, we distill the available evidence to
      summarize our position on the optimal use of available assays, and propose
      strategies for resolving cases with equivocal methylation status and a framework
      for incorporating this important assay into research and clinical practice.

PMID- 30189037
TI  - Moral Enhancement, Self-Governance, and Resistance.
AB  - John Harris recently argued that the moral bioenhancement proposed by Persson and
      Savulescu can damage moral agency by depriving recipients of their freedom to
      fall (freedom to make wrongful choices) and therefore should not be pursued. The
      link Harris makes between moral agency and the freedom to fall, however, implies
      that all forms of moral enhancement that aim to make the enhancement recipients
      less likely to "fall," including moral education, are detrimental to moral
      agency. In this article, I present a new moral agency-based critique against the
      moral bioenhancement program envisaged by Persson and Savulescu. I argue that the
      irresistible influences exerted by the bioenhancement program harm our
      capabilities for conducting accurate self-reflection and forming decisions that
      truly express our will, subsequently undermining our moral agency.

PMID- 30189038
TI  - Eight Kinds of Critters: A Moral Taxonomy for the Twenty-Second Century.
AB  - Over the coming century, the accelerating advance of bioenhancement technologies,
      robotics, and artificial intelligence (AI) may significantly broaden the
      qualitative range of sentient and intelligent beings. This article proposes a
      taxonomy of such beings, ranging from modified animals to bioenhanced humans to
      advanced forms of robots and AI. It divides these diverse beings into three moral
      and legal categories-animals, persons, and presumed persons-describing the moral
      attributes and legal rights of each category. In so doing, the article sets forth
      a framework for extending the concept of personhood well beyond its current
      boundaries, assigning moral standing to a variety of biological and nonbiological
      beings. The author concludes that six of the eight subgroups of such beings
      deserve to be treated as persons or as if they were persons, with full
      consideration for their presumed interests, rights, obligations, and capabilities
      for ethically significant agency and patiency.

PMID- 30189039
TI  - Are We Obliged to Enhance for Moral Perfection?
AB  - Suppose, we could take a pill that would turn us into morally better people.
      Would we have a duty to take such a pill? In recent years, a number of
      philosophers have discussed this issue. Most prominently, Ingmar Persson and
      Julian Savulescu have argued that we would have a duty to take such a pill. In
      this article, I wish to investigate the possible limits of a duty to take moral
      enhancement drugs through investigating the related question of whether it would
      be desirable to create a world populated entirely with morally perfect people. I
      argue, drawing on the work of Bernard Williams, Susan Wolf, and Michael Slote,
      that we have reason to be grateful that we do not live a world in which everyone
      is morally perfect, as this would prevent people from dedicating their lives to
      valuable nonmoral projects. I then argue that this thought should serve as a
      limitation on attempts to morally improve people through the use of technology.
      Finally, I explore the implications of this discussion for some of the less
      ambitious forms of moral enhancement currently being explored in the literature.
      I argue that these forms of enhancement give us no reason to worry about
      preventing valuable, morally imperfect ways of life. In fact, by acting as a
      shortcut to moral development, they might serve as an aid to help people fulfill
      valuable nonmoral goals in a way that is morally permissible.

PMID- 30189040
TI  - Why "Moral Enhancement" Isn't Always Moral Enhancement: The Case of Traumatic
      Brain Injury in American Vets.
AB  - In this article, I argue that as we learn more about how we might intervene in
      the brain in ways that impact human behavior, the scope of what counts as "moral
      behavior" becomes smaller and smaller because things we successfully manipulate
      using evidence-based science are often things that fall outside the sphere of
      morality. Consequently, the argument that we are morally obligated to morally
      enhance our neighbors starts to fall apart, not because humans should be free to
      make terrible choices, but because morality is not something subject to such
      manipulation. To illustrate my argument, I shall use the rise of veteran
      diversion courts in the United States as a putative instance of an intervention
      designed to change human behavior for the better. Part of my purpose in working
      my way through this case study is to demonstrate that many philosophers have the
      psychology of immoral action wrong.

PMID- 30189041
TI  - Can Prudence Be Enhanced?
AB  - Some bioethicists have argued that moral bioenhancement, complementing
      traditional means of enhancing individuals' moral dispositions, is essential if
      we are to survive as a species. Traditional means of moral enhancement have
      historically included civil legislation, socially recognized moral exemplars,
      religious teachings and disciplines, and familial upbringing. I explore the
      necessity and feasibility of pursuing methods of moral bioenhancement as a
      complement to such traditional means, grounding my analysis within a virtue
      theoretic framework. Specifically, I focus on the essential intellectual virtue
      for proper moral reasoning, prudence, and whether proposed methods of moral
      bioenhancement could facilitate the cultivation of this virtue within the psyches
      of moral agents. I conclude that certain means of bioenhancement may serve to
      augment the ability to reason prudentially and assist moral agents to align their
      wills with their higher-order rational desires, though such means require those
      higher-order desires to already have been formulated independently.

PMID- 30189042
TI  - Addressing Extreme Propensity Scores via the Overlap Weights.
AB  - The popular inverse probability weighting method in causal inference is often
      hampered by extreme propensity scores, resulting in biased estimates and
      excessive variance. A common remedy is to trim patients with extreme scores.
      However, such methods are often sensitive to the choice of cutoff points and
      discard a large proportion of the sample. The implications to bias and precision
      of the treatment effect estimate are unclear. These problems are mitigated by the
      newly developed overlap weighting method. Overlap weights emphasize the target
      population with the most overlap in observed characteristics between treatments,
      by continuously down-weighting the units in the tails of the propensity score
      distribution. We use simulations to compare overlap weights to standard inverse
      probability weighting with trimming, in terms of bias, variance and confidence
      interval coverage. A range of propensity score distributions are considered,
      including settings with substantial non-overlap and extreme values. To facilitate
      practical implementation, we further provide a consistent estimator for standard
      error of the treatment effect estimated using overlap weighting.

PMID- 30189043
TI  - Acute Kidney Injury After Burn: A Cohort Study From the Parkland Burn Intensive
      Care Unit.
AB  - Rationale & Objective: Acute kidney injury (AKI) is a common and morbid
      complication in patients with severe burn. The reported incidence of AKI and
      mortality in this population vary widely due to inconsistent and changing
      definitions. We aimed to examine the incidence, severity, and hospital mortality
      of AKI patients after burn using consensus criteria. Study Design: Retrospective
      cohort study of adults with thermal injury admitted to the Parkland burn
      intensive care unit (ICU) from 2008 to 2015. Setting & Participants: 1040 adult
      patients with burn admitted to the burn ICU. Predictor: AKI defined by KDIGO
      serum creatinine-criteria. Outcomes: Primary: hospital death; secondary: length
      of mechanical ventilation, ICU, and hospital stay. Measurements: All available
      serum creatinine measurements were used to determine the occurrence of AKI during
      the hospitalization. All relevant clinical data were collected. Results: The
      median total body surface area (TBSA) of burn was 16% (IQR: 6-29%). AKI occurred
      in 601 patients (58%; AKI stage 1, 60%; stage 2, 19.8%; stage 3, 10.5%; stage 3
      requiring renal replacement therapy [3-RRT], 9.7%). Patients with AKI had larger
      TBSA burn (median 20.5% vs. 11.0%; P < 0.001) and more mechanical ventilation and
      hospitalization days than patients without AKI. The hospital death rate was
      higher in those with AKI vs. those without AKI (19.7% vs 3.9%; P < 0.001) and
      increased by each AKI severity stage (P trend < 0.001). AKI severity was
      independently associated with hospital mortality in the small burn group (for
      TBSA <= 10%: stage 1 adjusted OR 9.3; 95% CI, 2.6-33.0; stage 2-3 OR, 35.0; 95%
      CI, 9.0-136.8; stage 3-RRT OR, 30.7; 95% CI, 4.2-226.4) and medium burn group
      (TBSA 10%-40%: stage 2-3 OR, 6.5; 95% CI, 1.9-22.1; stage 3-RRT OR, 35.1; 95% CI,
      8.2-150.3). AKI was not independently associated with hospital death in the large
      burn group (TBSA > 40%). Limitations: Urine output data were unavailable.
      Conclusions: AKI occurs frequently in patients after burn. Presence of and
      increasing severity of AKI are associated with increased hospital mortality. AKI
      appears to be independently and strongly associated with mortality in patients
      with TBSA <= 40%. Further investigation to develop risk-stratification tools
      tailoring this susceptible population is direly needed.

PMID- 30189045
TI  - Corrigendum.

PMID- 30189044
TI  - Cytokine Microdialysis for Real-Time Immune Monitoring in Glioblastoma Patients
      Undergoing Checkpoint Blockade.
AB  - BACKGROUND: Glioblastoma is the most common primary malignancy of the brain, with
      a dismal prognosis. Immunomodulation via checkpoint inhibition has provided
      encouraging results in non-CNS malignancies, but prediction of responders has
      proven to be challenging in glioblastoma patients. OBJECTIVE: To determine the
      proportion of patients who have a measurable increase of interferon gamma levels
      in brain tumor tissue after their first dose of nivolumab, and to evaluate the
      safety of using brain tumor microdialysis to monitor for immune response while
      evaluating the safety of the combination of anti-programmed death 1 (PD-1) and
      anti-lymphocyte activation gene 3 (LAG-3) checkpoint inhibition. METHODS: The
      study design is a single-center, nonrandomized phase 1 clinical trial. Up to 15
      adult patients with recurrent glioblastoma will be enrolled with the goal of 10
      patients completing the trial over an anticipated 18 mo. Patients will undergo
      biopsy; placement of microdialysis catheters and lumbar drains; treatment with
      anti-PD-1 checkpoint inhibition; comprehensive immune biomarker collection; tumor
      resection; and then treatment with anti-PD-1 and anti-LAG-3 checkpoint inhibition
      until progression. EXPECTED OUTCOMES: We expect interferon gamma levels to
      increase in the brain as measured via microdialysis in treated patients. Based on
      published reports, microdialysis in this patient population is expected to be
      safe, and anti-LAG-3 and anti-PD-1 combined will likely have a similar side
      effect profile to other checkpoint inhibitor combinations. DISCUSSION: The
      failure of recent trials of immune therapies in glioblastoma underscores the need
      to appropriately measure response in the treated tissue. This trial may provide
      insight on indicators of which patients will respond to immune therapy.

PMID- 30189046
TI  - Similarities and differences in the balances between leaf, xylem and phloem
      structures in Fraxinus ornus along an environmental gradient.
AB  - The plant carbon balance depends on the coordination between photosynthesis and
      the long-distance transport of water and sugars. How plants modify the allocation
      to the different structures affecting this coordination under different
      environmental conditions has been poorly investigated. In this study, we
      evaluated the effect of soil water availability on the allocation to leaf, xylem
      and phloem structures in Fraxinus ornus L. We selected small individuals of F.
      ornus (height ~2 m) from sites contrasting in soil water availability (wet vs
      dry). We measured how the leaf (LM) and stem + branch biomass (SBM) are cumulated
      along the stem. Moreover, we assessed the axial variation in xylem (XA) and
      phloem tissue area (PA), and in lumen area of xylem vessels (CAxy) and phloem
      sieve elements (CAph). We found a higher ratio of LM:SBM in the trees growing
      under drier conditions. The long-distance transport tissues of xylem and phloem
      followed axial patterns with scaling exponents (b) independent of site
      conditions. PA scaled isometrically with XA (b ~ 1). While CAxy was only
      marginally higher at the wet sites, CAph was significantly higher at the drier
      sites. Our results showed that under reduced soil water availability, F. ornus
      trees allocate relatively more to the leaf biomass and produce more conductive
      phloem, which is likely to compensate for the drought-related hydraulic
      limitations to the leaf gas exchanges and the phloem sap viscosity.

PMID- 30189047
TI  - Outcomes of Pediatric Central Nervous System Tuberculosis in California, 1993
      2011.
AB  - Background: Our goal was to describe the characteristics and posttreatment
      outcomes of pediatric patients with central nervous system (CNS) tuberculosis
      (TB) and to identify factors associated with poor outcome. Methods: We included
      children aged 0 to 18 years with CNS TB reported to the California TB registry
      between 1993 and 2011. Demographics, clinical characteristics, severity of
      disease at presentation (Modified Medical Research Council stage I, II, or III
      [III is most severe]), treatment, and outcomes during the year after treatment
      completion were abstracted systematically from the medical and public health
      records. Patient outcomes were categorized as good or poor on the basis of
      disability in hearing, vision, language, ambulation, and development and other
      neurologic deficits. Results: Among 151 pediatric CNS TB cases reported between
      1993 and 2011 in California for which records were available, 92 (61%) cases
      included sufficient information to determine outcome. Overall, 55 (60%) children
      had a poor outcome. After we adjusted for age (0 to 4 years), children with stage
      III severity (vs I or II; prevalence rate ratio [PRR], 1.4 [95% confidence
      interval (CI), 1.1-1.9]), a protein concentration of >100 mg/dL on initial lumbar
      puncture (PRR, 1.2 [95% CI, 1.03-1.4]), or infarct on neuroimaging (PRR, 1.2 [95%
      CI, 1.04-1.3]) were at increased risk for a poor outcome. In multivariate
      analysis, an age of 0 to 4 years (vs >4 years; PRR, 1.4 [95% CI, 1.2-1.7]) and a
      stage II or III Modified Medical Research Council score (vs stage I; PRR, 1.2
      [95% CI, 1.03-1.5]) remained significantly associated with poor outcome.
      Conclusions: Pediatric patients with CNS TB in California are left with high
      rates of disabling clinical sequelae after treatment. The identification of
      modifiable factors is critical for improving outcomes.

PMID- 30189048
TI  - Thymectomy in patients with myasthenia gravis increases the risk of autoimmune
      rheumatic diseases: a nationwide cohort study.
AB  - Objectives: Previous studies have shown myasthenia gravis (MG) and autoimmune
      rheumatic diseases (ARDs) share common pathogenetic mechanisms. Therefore, the
      present study investigated the possible relationship between MG and ARDs.
      Methods: We analysed Taiwanese medical data from the Registry of Catastrophic
      Illness and identified patients with MG. From the entire general population data
      of the National Health Insurance Research Database, we randomly selected a
      comparison cohort that was frequency-matched by age (in 5-year increments), sex,
      and index date. We analysed the risk of ARDs by using a Cox proportional hazards
      regression model stratified by sex, age and treatment. Results: In the present
      study, we enrolled 6478 patients with MG (58.03% women; mean age, 50.55 years)
      and 25 912 age- and sex-matched controls. The risk of total ARDs was 6.25 times
      higher in the MG cohort than in the non-MG cohort after adjustment for age and
      sex. Furthermore, the MG cohort was associated with a significantly higher risk
      of primary SS (pSS), SLE and other ARD types (adjusted hazard ratios: 15.84 [95%
      CI: 8.39, 23.91]; 11.32 [95% CI: 5.04, 25.429]; and 4.07 [95% CI: 1.31, 12.62],
      respectively). The MG cohort who underwent thymectomy had an increased risk of
      RA, pSS and SLE (adjusted hazard ratios: 4.41; 15.06; and 23.68, respectively).
      Conclusion: The present nationwide cohort study revealed an association between
      MG and incident ARDs. The MG cohort who underwent thymectomy had an increased
      risk of RA, pSS and SLE. Future studies are needed to elucidate the underlying
      pathogenesis and to translate this into clinical therapeutic options.

PMID- 30189049
TI  - Detection of Cervical Neoplasia by Human Papillomavirus Testing in an Atypical
      Squamous Cells-Undetermined Significance Population: Results of the Becton
      Dickinson Onclarity Trial.
AB  - Objectives: To determine clinical utility of Onclarity human papillomavirus (HPV)
      assay for atypical squamous cells-undetermined significance (ASC-US) triage, and
      the value of HPV genotyping within ASC-US. Methods: Women (n = 33,858; 21 years
      or older) had HPV testing using Onclarity and Hybrid Capture 2 (HC2). ASC-US
      individuals (n = 1,960, 5.8%) were referred to colposcopy. Results: Of ASC-US,
      39.1% were HPV positive by Onclarity; HPV 16 was the most prevalent genotype
      (7.4%). Cervical intraepithelial neoplasia grade 2 (CIN 2) and CIN 3+ prevalences
      were 4.4% and 2.2%, respectively. Onclarity had sensitivity for CIN 2+ (85.7%)
      and CIN 3+ (91.4%), and specificities for CIN 2+ (64.1%) and CIN 3+ (62.0%),
      similar to HC2. Risks for CIN 3+ were 16.1%, 2.8%, 2.5%, and 2.7% with HPV 16,
      18, 45, and 11 other genotypes, respectively. Conclusions: Onclarity is
      clinically validated for ASC-US triage. Through risk stratification, genotyping
      could help identify women at highest risk for CIN 3+.

PMID- 30189050
TI  - Deciphering beta-lactamase-independent beta-lactam resistance evolution
      trajectories in Pseudomonas aeruginosa.
AB  - Background: While resistance related to the expression of beta-lactamases, such
      as AmpC from Pseudomonas aeruginosa, has been deeply studied, this work addresses
      the gap in the knowledge of other potential bacterial strategies to overcome the
      activity of beta-lactams when beta-lactamases are not expressed. Methods: We
      analysed beta-lactam resistance evolution trajectories in a WT strain and in
      isogenic mutants either lacking AmpC (AmpC mutant) or unable to express it (AmpG
      mutant), exposed to increasing concentrations of ceftazidime for 7 days in
      quintuplicate experiments. Characterization of evolved lineages included
      susceptibility profiles, whole-genome sequences, resistance mechanisms, fitness
      (competitive growth assays) and virulence (Caenorhabditis elegans model).
      Results: Development of resistance was faster for the WT strain but, after 7
      days, all strains reached clinical ceftazidime resistance levels. The main
      resistance mechanism in the WT strain was ampC overexpression, due to mutations
      in dacB and ampD or mpl. In contrast, ampC overexpression did not evolve in any
      of the AmpG lineages. Moreover, sequencing of the DeltaAmpC and DeltaAmpG evolved
      lineages revealed alternative resistance mutations (not seen in WT lineages) that
      included, in all cases, large (50-600 kb) deletions of specific chromosomal
      regions together with mutations leading to beta-lactam target [ftsI (PBP3)]
      modification and/or the overexpression or structural modification of the efflux
      pump MexAB-OprM. Finally, evolved lineages from the AmpC and, especially, AmpG
      mutants showed a reduced fitness and virulence. Conclusions: In addition to
      providing new insights into beta-lactam resistance mechanisms and evolution, our
      findings should be helpful for guiding future strategies to combat P. aeruginosa
      infections.

PMID- 30189051
TI  - Commentary: Inpatient and Post-Discharge Outcomes Following Elective Craniotomy
      for Mass Lesions.

PMID- 30189052
TI  - Pelvic Fracture Care.
AB  - While combat-related pelvis fractures are more commonly open, higher energy, and
      complex in pattern than those seen in the civilian setting, the principles of
      management are similar. The primary differences are related to the austere
      setting in which the initial management takes place, and the lack of resources
      typically available. Initial management consists of cessation of hemorrhage,
      along with the multi-disciplinary prioritized management of associated injuries,
      and skeletal stabilization. This is most commonly achieved with a compressive
      sheet or pelvic binder, with pelvic external fixation when resources allow, and
      debridement of open wounds as necessary. Definitive, internal fixation is delayed
      until the patient arrives at a higher echelon of care.

PMID- 30189053
TI  - Hyperkalemia and Dialysis in the Deployed Setting.
AB  - Acute kidney injury is a recognized complication of combat trauma. The
      complications associated with acute kidney injury, such as life-threatening
      hyperkalemia, are usually delayed in onset. In the recent conflicts, rapid
      evacuation of U.S. and coalition personnel generally resulted in these
      complications occurring at higher echelons of care where renal replacement
      therapies were available. In the future however, deployed providers may not have
      this luxury and should be prepared to temporize patients while they await
      transport. In this clinical practice guideline, recommendations are made for the
      management of patients with, or at risk for, acute kidney injury and hyperkalemia
      in the austere, deployed environment.

PMID- 30189054
TI  - Emergency Resuscitative Thoracotomy in the Combat or Operational Environment.
AB  - Resuscitative thoracotomy has been extensively described in the civilian trauma
      literature and has a high mortality rate, due largely to the nature of the
      injuries leading to arrest. The survival rates are generally highest (10-30%) for
      penetrating truncal injuries and patients who arrive with vital signs and proceed
      to arrest or who have impending arrest. They are significantly lower (less than
      5%) for blunt trauma victims, particularly those who arrest in the field or
      during transport (1% or less). In addition, the likelihood of survival with
      intact neurologic function is significantly lower than the overall survival
      rates, particularly for blunt trauma victims and for prehospital arrest.

PMID- 30189055
TI  - Amputation: Evaluation and Treatment.
AB  - Combat extremity injury and amputation is a life threatening injury. Initial
      surgical care should focus on hemostasis followed by irrigation and debridement
      of contaminated and nonviable tissue. Preservation of limb length begins at the
      initial surgical procedure, to include retention of atypical soft tissue flaps
      for later reconstruction and treatment of proximal fractures. Serial irrigation
      and debridements are required throughout the MEDEVAC system as the evolving zone
      of injury becomes more mature, followed by the appropriate timing of closure
      outside the combat theater.

PMID- 30189056
TI  - High Bilateral Amputations and Dismounted Complex Blast Injury (DCBI).
AB  - High, combat-related bilateral lower extremity amputations rarely occur in
      isolation. Dismounted complex blast injury is a devastating and life-threatening
      constellation of multisystem injuries most commonly due to dismounted contact
      with improvised explosive devices. Rapid damage control resuscitation and surgery
      are essential to improve patient survival and minimize both early complications
      and late sequelae. A coordinated team approach is essential to provide
      simultaneous airway management, volume resuscitation (ideally with whole blood or
      ratio transfusion), and immediate control of life-threatening hemorrhage.
      Temporary aortic or iliac vessel clamping during concurrent exploratory or
      vascular control laparotomy is frequently required. Stabilization of unstable
      pelvic fractures is then performed, followed by debridement and irrigation of all
      wounds, which should be left open, and subsequent provisional stabilization of
      long bone fractures. The goal of the initial surgical resuscitative endeavor is
      rapid concurrent control of all sources of hemorrhage to avoid the lethal triad
      of acidosis, hypothermia and coagulopathy. To this end, multiple surgeons or
      surgical teams should be utilized whenever feasible. Patients then require
      ongoing resuscitation followed by early and frequent return to the operating
      suite throughout the evacuation chain. Utilizing this approach, a high survival
      rate with reasonable functional outcomes is achievable despite the extreme
      severity of the DCBI pattern.

PMID- 30189057
TI  - The Use of Frozen and Deglycerolized Red Blood Cells.
AB  - Deglycerolized red blood cells have been used by the U.S. military for half a
      century, starting with the Vietnam War. Deglycerolized red blood cells have a
      frozen storage life of 10 years, but require special equipment to thaw and
      deglycerolize. The available data show no difference in either efficacy with
      complications when compared to standard product red blood cells.

PMID- 30189058
TI  - Frostbite and Immersion Foot Care.
AB  - Historically, cold injury, hypothermia, and frostbite have been severe problems
      for military units on the battlefield. Kenneth D. Orr and David C. Fainer
      captured these difficulties in their book, Cold Injuries in Korea During Winter
      of 1950-51, still cited in military medical readiness training. While not common
      in modern conflicts, the potential exists for large numbers of these casualties
      in war and during training.

PMID- 30189059
TI  - Prevention of Deep Venous Thromboembolism.
AB  - The nature of many combat wounds puts patients at a high risk of developing deep
      venous thrombosis (DVT) and pulmonary embolism (PE), which fall under the broader
      disease category of venous thromboembolism (VTE). In addition to the
      hypercoagulable state induced by trauma, massive injuries to the extremities,
      prolonged immobility, and long fixed wing transport times to higher echelons of
      care are unique risk factors for venous thromboembolism in the combat-injured
      patient. These risk factors mandate aggressive prophylaxis for DVT and PE that
      can effectively be achieved by the use of lower extremity sequential compression
      devices and low dose unfractionated heparin or low molecular weight heparin. In
      addition, inferior vena cava filters are often used for PE prophylaxis when
      chemical DVT prophylaxis fails or is contraindicated. The following Department of
      Defense (DoD) Joint Trauma System (JTS) Clinical Practice Guideline (CPG)
      discusses the current recommendations for the prevention of DVT and PE including
      the use of inferior vena cava filters (IVCFs).

PMID- 30189060
TI  - Radiology: Imaging Trauma Patients in a Deployed Setting.
AB  - Medical imaging plays a critical role in the rapid diagnosis, effective triage,
      and management of complex poly-trauma patients. High-quality medical imaging can
      be accomplished successfully in a deployed or wartime setting. Due to advances in
      aggressive resuscitation techniques and the speed of the latest generation
      computed tomography scanners (64-detector and beyond), rapid trauma scans
      utilizing computed tomography and ultrasound imaging can routinely be performed
      prior to taking the patient to the operating room potentially providing the
      trauma team with lifesaving information. This clinical practice guideline
      provides an overview of the imaging modalities available in austere settings, the
      equipment required, and the role that each plays in triaging and diagnosis of the
      acutely injured poly-trauma patients.

PMID- 30189061
TI  - Whole Blood Transfusion.
AB  - Whole blood is the preferred product for resuscitation of severe traumatic
      hemorrhage. It contains all the elements of blood that are necessary for oxygen
      delivery and hemostasis, in nearly physiologic ratios and concentrations. Group O
      whole blood that contains low titers of anti-A and anti-B antibodies (low titer
      group O whole blood) can be safely transfused as a universal blood product to
      patients of unknown blood group, facilitating rapid treatment of exsanguinating
      patients. Whole blood can be stored under refrigeration for up to 35 days, during
      which it retains acceptable hemostatic function, though supplementation with
      specific blood components, coagulation factors or other adjuncts may be necessary
      in some patients. Fresh whole blood can be collected from pre-screened donors in
      a walking blood bank to provide effective resuscitation when fully tested stored
      whole blood or blood components are unavailable and the need for transfusion is
      urgent. Available clinical data suggest that whole blood is at least equivalent
      if not superior to component therapy in the resuscitation of life-threatening
      hemorrhage. Low titer group O whole blood can be considered the standard of care
      in resuscitation of major hemorrhage.

PMID- 30189062
TI  - Burn Casualty Care in the Deployed Setting.
AB  - Management of wartime burn casualties can be very challenging. Burns frequently
      occur in the setting of other blunt and penetrating injuries. This clinical
      practice guideline provides a manual for burn injury assessment, resuscitation,
      wound care, and specific scenarios including chemical and electrical injuries in
      the deployed or austere setting. The clinical practice guideline also reviews
      considerations for the definitive care of local national patients, including
      pediatric patients, who are unable to be evacuated from theater. Medical
      providers are encouraged to contact the US Army Institute of Surgical Research
      (USAISR) Burn Center when caring for a burn casualty in the deployed setting.

PMID- 30189063
TI  - Catastrophic Non-Survivable Brain Injury Care-Role 2/3.
AB  - A catastrophic brain injury is defined as any brain injury that is expected to
      result in permanent loss of all brain function above the brain stem level. These
      clinical recommendations will help stabilize the patient so that they may be
      safely evacuated from theater. In addition to cardiovascular and hemodynamic
      goals, special attention must be paid to their endocrine dysfunction and its
      treatment-specifically steroid, insulin and thyroxin (t4) replacement while
      evaluating for and treating diabetes insipidus. Determining the futility of care
      coupled with resource management must also be made at each echelon. Logistical
      coordination and communication is paramount to expedite these patients to higher
      levels of care so that there is an increased probability of reuniting them with
      their family.

PMID- 30189064
TI  - Inhalation Injury and Toxic Industrial Chemical Exposure.
AB  - Toxic industrial chemicals include chlorine, phosgene, hydrogen sulfide, and
      ammonia have variable effects on the respiratory tract, and maybe seen alone or
      in combination, secondary to inhalation injury. Other considerations include the
      effects of cyanide, carbon monoxide, and fire suppressants. This Clinical
      Practice Guideline (CPG) will provide the reader with a brief overview of these
      important topics and general management strategies for each as well as for
      inhalation injury. Chlorine, phosgene, hydrogen sulfide, and ammonia are either
      of intermediate or high water solubility leading to immediate reactions with
      mucous membranes of the face, throat, and lungs and rapid symptoms onset after
      exposure. The exception to rapid symptom onset is phosgene which may take up to a
      day to develop severe acute respiratory distress syndrome. Management of these
      patients includes early airway management, lung-protective ventilator strategies,
      aggressive pulmonary toilet, and avoidance of volume overload.

PMID- 30189065
TI  - Blunt Abdominal Trauma, Splenectomy, and Post-Splenectomy Vaccination.
AB  - Unlike penetrating abdominal injuries where the decision to operate is relatively
      straight forward, those combat casualties that sustain blunt abdominal trauma
      offer more of a diagnostic and clinical challenge. For unstable patients with a
      positive focused abdominal sonography in trauma or diagnostic peritoneal lavage,
      exploratory laparotomy should be undertaken immediately. All grade IV-V splenic
      injuries should undergo splenectomy, patients undergoing attempted splenic
      salvage should be monitored in the Role 3 facility and embolization of such
      splenic injuries may be considered if available. Patients who fail non-operative
      management of the spleen require splenectomy at the Role 3 prior to aeromedical
      evacuation. Overwhelming post-splenectomy infection is a serious disease that can
      progress from a mild flu-like illness to fulminant sepsis in a short period of
      time. Although relatively rare, it has a high mortality rate with delayed or
      inadequate treatment. All splenectomized patients and those deemed to be
      functionally asplenic should be vaccinated within 14 days from splenectomy and
      prior to aeromedical evacuation.

PMID- 30189066
TI  - Anesthesia for Trauma Patients.
AB  - An improved understanding of the pathophysiology of combat trauma has evolved
      over the past decade and has helped guide the anesthetic care of the trauma
      patient requiring surgical intervention. Trauma anesthesia begins before patient
      arrival with warming of the operating room, preparation of anesthetic medications
      and routine anesthetic machine checks. Induction of anesthesia must account for
      potential hemodynamic instability and intubation must consider airway trauma.
      Maintenance of anesthesia is accomplished with anesthetic gas, intravenous
      infusions or a combination of both. Resuscitation must precede or be ongoing with
      the maintenance of anesthesia. Blood product transfusion, antibiotic
      administration, and use of pharmacologic adjuncts (e.g., tranexamic acid,
      calcium) all occur simultaneously. Ventilatory strategies to mitigate lung injury
      can be initiated in the operating room, and resuscitation must be effectively
      transitioned to the intensive care setting after the case. Good communication is
      vital to efficient patient movement along the continuum of care. The
      resuscitation that is undertaken before, during and after operative management
      must incorporate important changes in care of the trauma patient. This Clinical
      Practice Guideline hopes to provide a template for care of this patient
      population. It outlines a method of anesthesia that incorporates the induction
      and maintenance of anesthesia into an ongoing resuscitation during surgery for a
      trauma patient in extremis.

PMID- 30189067
TI  - Airway Management for Trauma Patients.
AB  - Trauma airway management is a critical skill for medical providers supporting
      combat casualties since it is an integral component of damage control
      resuscitation and surgery. This clinical practice guideline presents methods for
      optimizing the airway management of patients with traumatic injury in the
      operational medical treatment facility environment. The guidelines represent the
      knowledge and experience of 10 co-authors from 3 allied countries representing
      Emergency Medicine, Surgery and Anesthesia.

PMID- 30189068
TI  - MRI in Management of Mild TBI/Concussion in the Deployed Setting.
AB  - Magnetic resonance imaging (MRI) has specific limitations in theater and has
      unique requirements for its safe use with patients which require additional
      technician training and strict adherence to MRI-specific safety protocols.
      Neuroimaging is recommended for the evaluation of service members with clinical
      red flags new onset or persistent or worsening symptoms, and individuals whose
      recovery is not progressing as anticipated. This article is a brief discussion of
      when MRI is appropriate.

PMID- 30189069
TI  - Unexploded Ordnance Management.
AB  - The purpose of this Clinical Practice Guide is to provide details on the
      procedures to safely remove unexploded ordnance from combat patients, both loose
      and impaled, to minimize the risks to providers and the medical treatment
      facility while ensuring the best outcome for the patient. Military ordnance, to
      include bullets, grenades, flares, and explosive ordnance, retained by a patient
      can be a risk to all individuals and equipment along the continuum of care. This
      is especially true from the point of injury to the first treatment facility.
      Management of patients with unexploded ordnance either on or in their body is a
      rare event during combat surgery. Loose munitions are usually noted and easily
      removed prior to the patient receiving medical treatment. However, impaled
      munitions provide a significant challenge. These are usually caused by large
      caliber, high-velocity projectiles. Patients who survive to arrive at a treatment
      facility must be triaged safely and simultaneously treated appropriately to
      ensure both the survival of the patient and the treatment team. Between WWII and
      the Somalia conflict, there have been 36 reported cases of unexploded ordnance
      from U.S. soldiers. Since 2005, there have been six known cases during the U.S.
      wars in Afghanistan and Iraq and one additional case in Pakistan. Optimal
      outcomes require a basic knowledge of explosives and triggering mechanisms, as
      well as adherence to basic principles of trauma resuscitation and surgery.

PMID- 30189070
TI  - Damage Control Resuscitation.
AB  - Damage control resuscitation (DCR) is a strategy for resuscitating patients from
      hemorrhagic shock to rapidly restore homeostasis. Efforts are focused on blood
      product transfusion with whole blood or component therapy closely approximating
      whole blood, limited use of crystalloid to avoid dilutional coagulopathy,
      hypotensive resuscitation until bleeding control is achieved, empiric use of
      tranexamic acid, prevention of acidosis and hypothermia, and rapid definitive
      surgical control of bleeding. Patients receiving uncrossmatched Type O blood in
      the emergency department and later receiving cumulative transfusions of 10 or
      more red blood cell units in the initial 24-hour post-injury (massive
      transfusion) are widely recognized as being at increased risk of morbidity and
      mortality due to exsanguination. Ideally, these patients should be rapidly
      identified, however anticipating transfusion needs is challenging. Useful
      indicators of massive transfusion reviewed in this guideline include: systolic
      blood pressure <110 mmHg, heart rate > 105 bpm, hematocrit <32%, pH < 7.25,
      injury pattern (above-the-knee traumatic amputation especially if pelvic injury
      is present, multi-amputation, clinically obvious penetrating injury to chest or
      abdomen), >2 regions positive on Focused Assessment with Sonography for Trauma
      (FAST) scan, lactate concentration on admission >2.5, admission international
      normalized ratio >=1.2-1.4, near infrared spectroscopy-derived StO2 < 75% (in
      practice, rarely available), BD > 6 meq/L. Unique aspects of out-of-hospital DCR
      (point of injury, en-route, and remote DCR) and in-hospital (Medical Treatment
      Facilities: Role 2b/Forward surgical teams - role 3/ combat support hospitals)
      are reviewed in this guideline, along with pediatric considerations.

PMID- 30189071
TI  - Treatment of Suspected Invasive Fungal Infection in War Wounds.
AB  - Invasive fungal wound infections (IFIs) were an unexpected complication
      associated with blast-related wounds during Operation Enduring Freedom. Between
      2010 and 2012, IFI incidence rates were as high as 10-12% for patients injured
      during Operation Enduring Freedom and admitted to the intensive care unit at the
      Landstuhl Regional Medical Center. Independent risk factors for the development
      of IFIs include dismounted blast injuries, above knee amputations and massive
      (>20 units) packed red blood cell transfusions within 24 hours after injury. The
      Joint Trauma System developed a Clinical Practice Guideline on IFI prevention,
      identification and management. Aggressive and frequent surgical debridement
      remains the primary therapy accompanied by topical antifungal therapy (e.g.,
      Dakins solution). Empiric systemic antifungal therapy with both liposomal
      amphotericin B and an intravenous broad-spectrum triazole (e.g., voriconazole or
      posaconazole) should be administered when there is strong suspicion of IFI based
      on the occurrence of recurrent wound necrosis following serial surgical
      debridements, since many cases involve multiple fungal species. Other
      recommendations include: (1) early tissue sampling for wound histopathology and
      fungal cultures, (2) early consultation with infectious disease specialists, and
      (3) coordination with surgical pathology and clinical microbiology.

PMID- 30189072
TI  - Infection Prevention in Combat-Related Injuries.
AB  - Wound infections play an important role in the morbidity and mortality of service
      members injured in combat. The exigent and often long road to recovery can be
      complicated by healthcare-associated infections caused by multidrug-resistant
      organisms. The outcome is not only financially taxing but also can be life
      threatening. This Clinical Practice Guideline (CPG) will provide the reader with
      a brief overview of this topic, easy and equitable strategies to implement, and
      significantly reduce the exposure and possible contamination and spread of life
      threatening organisms in combat wounds. The table and guidance will provide easy
      step-wise approach in management of different challenging scenarios to help
      control spread of infection down range and at every level of medical treatment
      facility involved in patient transport to the ultimate institution.

PMID- 30189073
TI  - Nutritional Support Using Enteral and Parenteral Methods.
AB  - The purpose of this Clinical Practice Guideline is to provide an approach for
      optimal nutritional support in the postinjury period for those injured in combat.
      Indications and contraindications for enteral and parenteral nutrition are
      addressed. Timing of nutritional support, nutritional goals, energy requirements,
      and ideal formula selection for various types of traumatic injuries are
      addressed. Challenges encountered providing nutrional support for the
      traumatically injured in the deployed environment are also discussed.

PMID- 30189074
TI  - Drowning Management.
AB  - Highly skilled swimmers and aquatically adaptable service members such as U.S.
      Navy Divers, Sea, Air and Land (SEAL) Teams, and Explosive Ordnance Disposal
      (EOD) technicians, die every year from drowning. Drowning is the cause of over
      500,000 deaths annually across the globe. This Clinical Practice Guideline (CPG)
      provides an overview of drowning and associated conditions based on the best
      available current medical evidence. Unlike basic life support and advanced
      cardiac life support protocols, rescue breathing should be initiated prior to
      chest compressions to re-expand water-filled alveoli. These guidelines should be
      used as a standardized framework to guide first responders, prehospital emergency
      medical service personnel, and medical department personnel in evaluating,
      diagnosing, and managing common in water pathologies.

PMID- 30189075
TI  - Cervical and Thoracolumbar Spine Injury Evaluation, Transport, and Surgery in the
      Deployed Setting.
AB  - This Cervical and Thoracolumbar Spine Injury Evaluation, Transport, and Surgery
      Clinical Practice Guideline (CPG) is designed to provide guidance to the deployed
      provider when they are treating a combat casualty who has sustained a spine or
      spinal cord injury. The CPG objective for the treatment and the movement of these
      patients is to maintain spinal stability through transport, perform decompression
      when urgently needed, achieve definitive stabilization when appropriate, avoid
      secondary injury, and prevent deterioration of the patient's neurological
      condition. Thorough and accurate documentation of the patient's neurological
      examination is crucial to ensure appropriate management decisions are made as the
      patient transits through the evacuation system. The use of this CPG should be in
      conjunction with good clinical judgment.

PMID- 30189076
TI  - Acute Extremity Compartment Syndrome and the Role of Fasciotomy in Extremity War
      Wounds.
AB  - Acute compartment syndrome (CS) is a frequent and potentially devastating
      complication of blunt and penetrating extremity injuries. Extremity war injuries
      are particularly susceptible to CS due to associated vascular injuries; high
      Injury Severity Score; extensive bone and soft tissue injury; and frequent
      transportation that may limit close monitoring of the injured extremity.
      Treatment consists of prompt fasciotomy of all compartments in the involved
      segment, over their full length. Delayed or incomplete fasciotomy is associated
      with worse outcomes, including muscle necrosis, infection, and amputation.
      Enhanced pre-deployment training of surgeons decreases the need for revision
      fasciotomy at higher echelons of care and should be continued in future
      conflicts. We recommend the liberal use of prophylactic fasciotomy prior to
      aeromedical evacuation and after limb reperfusion. For leg fasciotomy, we
      recommend a two-incision approach as it is more reproducible and allows easy
      vascular exposure when necessary.

PMID- 30189077
TI  - Wartime Vascular Injury.
AB  - Wartime vascular injury can be particularly challenging due to the complexity of
      the case, concomitant injuries, resource limitations, and often lack of expertise
      of the operating surgeon. The proliferation of vascular shunting has been of
      particular importance as a damage control surgery technique to restore perfusion
      and temporize the immediate need for definitive repair necessary for limb
      salvage, particularly in austere locations. Diagnosis of vascular injury can be
      made using a variety of techniques, from physical examination to ankle-brachial
      indices to the use of CT angiography or invasive angiographic techniques.
      Operative planning and judgment are therefore critical in deciding both how and
      whether to operate. Surgeons likely to deploy should take every opportunity to
      practice vascular exposures and techniques through clinical practice and
      laboratory courses.

PMID- 30189078
TI  - JTS CPG Development Process.

PMID- 30189079
TI  - Orthopedic Trauma: Extremity Fractures.
AB  - Fractures continue to account for a large proportion of combat-related injuries.
      The basic tenets of irrigation, debridement, soft tissue care, and vigilant
      monitoring/fasciotomy for acute compartment syndrome persist. Closed management
      of fractures with splinting or casting is acceptable. If time and facility allow,
      external fixation of fractures offer many advantages over closed treatment but
      require knowledge, experience and skill in the safe placement of pins. The care
      of host nationals presents unique challenges and deployed surgeons must be
      flexible and resourceful in these situations.

PMID- 30189080
TI  - Military Preventable Death Conceptual Framework: A Systematic Approach for
      Reducing Battlefield Mortality.
AB  - The National Academies of Sciences, Engineering, and Medicine Report on Zero
      Preventable Deaths highlighted the need for a military and civilian partnership
      to take lessons learned from the wars in Iraq and Afghanistan and incorporate
      them into a national learning trauma care system. One of the specific objectives
      in the report was to establish military preventable death metrics. Upon further
      inspection, it became apparent that the Department of Defense did not have an
      established methodology to reliably estimate and report preventable death metrics
      and opportunities to improve the military trauma care system. Over the last year,
      clinical and non-clinical subject matter experts from the Joint Trauma System and
      Armed Forces Medical Examiners System began the process of establishing a
      standard military preventable death review process to meet the objective outlined
      in the report. Based on an assessment to understand methodological best practices
      for preventable death reviews, this manuscript presents the conceptual framework
      that is guiding our effort to establish the first ever battle-related mortality
      surveillance system with preventable death metrics and opportunities to improve
      the trauma care system.

PMID- 30189082
TI  - The Joint Trauma System: History in the Making.

PMID- 30189081
TI  - Trauma Management of Military Working Dogs.
AB  - There are about 2,500 war and military service dogs in service, with about 700
      serving at any given time overseas. Military Working Dogs (MWDs) are critical
      assets for military police, special operations units, and others operating in
      today's combat environment. The expectation, given the significant combat
      multiplier impact of these dogs and the intense bond between the handler and dog,
      is that injured working dogs will receive the same level of care as any injured
      U.S. military personnel. Veterinary care is available at multiple locations
      throughout theater, and the veterinary healthcare team is the MWD's primary
      provider. Yet, human healthcare providers (HCPs) may be the only medical
      personnel available to MWDs that are gravely ill or injured. As most HCPs are
      unfamiliar with medical care of dogs, the Joint Trauma System published a
      Clinical Practice Guideline (CPG), a set of detailed clinical guidelines for
      managing life-threatening problems of MWDs encountered in combat operations. The
      CPG is available at the JTS website. This article is covers the most common
      urgent MWD care challenges HCPs may face.

PMID- 30189083
TI  - Neurosurgery and Medical Management of Severe Head Injury.
AB  - Management of the patient with moderate to severe brain injury in any environment
      can be time consuming and resource intensive. In the austere or hostile
      environment, the challenges to deliver care to this patient population are
      magnified. These guidelines have been developed by acknowledging commonly
      recognized recommendations for neurosurgical and neuro-critical care patients and
      augmenting those evaluations and interventions based on the experience of
      neurosurgeons, trauma surgeons, and intensivists who have delivered care during
      recent coalition conflicts.

PMID- 30189084
TI  - The Joint Trauma System and the Fog of War.

PMID- 30189085
TI  - The DoD Trauma Registry Versus the Electronic Health Record.
AB  - There is a widely prevailing belief that electronic health records and data
      registries are the same, or that registries can be replaced by electronic health
      records given the advances in technology. While information systems have
      revolutionized documentation of medical care, distinctions continue to exist.
      This article will clear the confusion between the two systems, using the Joint
      Trauma System's (JTS) Department of Defense (DoD) Trauma Registry (DoDTR), the
      approved enterprise wide trauma registry for the military, as an example.

PMID- 30189086
TI  - Aural Blast Injury/Acoustic Trauma and Hearing Loss.
AB  - Hearing is a critical sense to military performance. The ability to detect,
      identify, and localize sounds, the ability to maintain spatial awareness on the
      battlefield and the awareness to control one's own noise production can be vital
      to troop's stealth, survivability, and lethality. Hazardous noise is an
      environmental public health threat encountered in training at war, and in many
      off-duty activities. The risk to hearing and the resultant damage from any of
      these hazardous exposures is generally invisible, insidious and cumulative.
      Regardless of the source of injury, hearing loss degrades the sensor that
      integrates Service Members with their environment, provides for unity of effort,
      and ensures command and control.Acoustic trauma-induced hear loss and tinnitus
      are the two most prevalent disabilities in veterans, with over 765,000 cases in
      the Gulf War era alone. To counter this threat, it is necessary to push for early
      identification and early intervention through a trusted surveillance system.
      Success will require advocacy, education, and encouragement of self-reporting for
      evaluation following symptomatic noise exposures. This Clinical Practice
      Guideline (CPG) is a step to ensure the hearing health, readiness, protection,
      and care of Service Members. This will in turn optimize troop performance and
      minimize injury risk and mishap.

PMID- 30189087
TI  - Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) for Hemorrhagic
      Shock.
AB  - This clinical practice guideline (CPG) reviews the range of accepted management
      approaches to profound shock and post-traumatic cardiac arrest and establishes
      indications for considering Resuscitative Endovascular Balloon Occlusion of the
      Aorta (REBOA) as a hemorrhage control adjunct. The specific management approach -
      within the parameters of mission, resources, and tactical situation - will depend
      on the casualty's physical location, mechanism and pattern of injury, and the
      experience level of the surgeon. The optimal management strategy is best
      determined by the surgeon at the bedside.

PMID- 30189089
TI  - The Joint Trauma System Teams Dedicated to Optimizing Combat Casualty Care.

PMID- 30189088
TI  - Acute Respiratory Failure.
AB  - Acute respiratory distress syndrome (ARDS) is a condition affecting critically
      ill patients, characterized by pulmonary inflammation and defects in oxygenation
      due to either direct or indirect injury to the lungs. These guidelines will
      define the diagnosis and management of ARDS, particularly among combat casualties
      and patients in the deployed environment. The cornerstone of management of ARDS
      involves maintaining adequate oxygenation while avoiding further pulmonary injury
      through lung-protective ventilation. Additional strategies for advanced
      respiratory failure, such as prone positioning, neuromuscular blockade, and
      extracorporeal membrane oxygenation will be reviewed here as well. Particularly
      important to the care of the patient with ARDS in the deployed environment is a
      familiarity with the challenges and indications for transport/aeromedical
      evacuation.

PMID- 30189090
TI  - Worsening of the disability grade during leprosy treatment: prevalence and its
      determinants in Southern Nigeria.
AB  - Background: In Nigeria, little is known about the development of new or
      additional physical disability during leprosy treatment. The objective of this
      study was to determine the prevalence and evaluate factors associated with
      worsening of physical disability during leprosy treatment in Nigeria. Methods:
      This was a retrospective cohort study conducted among leprosy patients treated in
      six referral facilities in six States in Nigeria between January 2011 and
      December 2015. Multivariable logistic regression analysis was used to identify
      predictors of worsening disability after treatment. Results: Of 984 leprosy
      patients who completed treatment, the mean age of the patients was 39.8+/-17.6
      years and 57.4% (565/984) of them were male. Also, 51.6% (508/984) of the
      patients had either grade 1 or 2 disability at diagnosis, but this declined to
      30.8% (303/984) following treatment (p<0.001). Overall, 4.7% (46/984) of the
      cases developed new or additional disability (or worsening disability) during
      treatment. The cases with the greatest odds for developing worsening physical
      disability were patients from the southwest (adjusted odds ratio [aOR] 15.9; 95%
      CI 3.8-67.4) and southeast zones (aOR 4.7; 95% CI 1.1-19.2), and patients who had
      a leprosy reaction requiring additional corticosteroid therapy (aOR 11.7; 95% CI
      4.4-31.2). Conclusion: Sustained capacity building for health professionals on
      better monitoring and management of leprosy and its complications is strongly
      recommended in Nigeria.

PMID- 30189091
TI  - Physical activity is not related to risk of early menopause in a large
      prospective study.
AB  - STUDY QUESTION: Is physical activity associated with incident early menopause?
      SUMMARY ANSWER: Physical activity is not associated with incident early
      menopause. WHAT IS KNOWN ALREADY: Lifestyle factors such as physical activity may
      influence menopause timing, but results from prior research are inconsistent.
      STUDY DESIGN, SIZE, DURATION: We evaluated the association between physical
      activity and the occurrence of early natural menopause in a prospective cohort
      study, the Nurses' Health Study II. Women were followed prospectively from 1989
      to 2011. PARTICIPANTS/MATERIALS, SETTING, METHODS: Our analysis included 107 275
      women who were premenopausal at baseline. Menopause status was self-reported
      biennially. Time per week participating in specific activities was reported
      approximately every 4 years and used to calculate metabolic task hours per week
      (MET h/week). We used Cox proportional hazards model to evaluate the association
      between physical activity and incidence of natural menopause before age 45 years
      while controlling for potential confounding factors. MAIN RESULTS AND THE ROLE OF
      CHANCE: There were 2 786 study members who experienced menopause before the age
      of 45. After adjustment for age, smoking and other factors, we observed no
      association between adulthood physical activity and early menopause. For example,
      compared to women reporting <3 MET h/week, the hazard ratio for women in the
      highest category (>=42 MET h/week) of cumulatively-averaged total physical
      activity was 0.89 (95% confidence interval: 0.76-1.04; P-trend: 0.26). Neither
      moderate nor strenuous activity in adolescence and young adulthood were related
      to risk. The relation of physical activity and early menopause did not vary
      across strata of body mass index or smoking status. LIMITATIONS, REASONS FOR
      CAUTION: Physical activity and menopausal status were self-reported, but repeated
      assessment of physical activity and prospective report of menopause status likely
      reduce the potential for non-differential misclassification. While the majority
      of our study participants were white, it is unlikely that the physiological
      relation of activity and early menopause varies by ethnicity. WIDER IMPLICATIONS
      OF THE FINDINGS: Findings from our large prospective study do not support an
      important association between physical activity and early menopause. STUDY
      FUNDING/COMPETING INTEREST(S): This project was supported by UM1CA176726 and
      R01HD078517 from the National Institutes of Health, Department of Health and
      Human Services. No competing interests are declared. TRIAL REGISTRATION NUMBER:
      N/A.

PMID- 30189092
TI  - Association between preceding viral respiratory infection and subsequent
      respiratory illnesses among children: A prospective cohort study in the
      Philippines.
AB  - Background: Acute respiratory infection (ARI) is of great concern in public
      health. It remains unclear whether viral infections can affect the host's
      susceptibility to subsequent ARIs. Methods: A prospective cohort study on ARIs of
      children below five years old was conducted in the Philippines from 2014 to 2016.
      The respiratory symptoms were recorded daily and nasopharyngeal swabs were
      collected at both household and health facilities. The specimens were tested for
      respiratory viruses. We then determined whether viral etiology was associated
      with the severity of the present ARI and whether previous viral infections was
      associated with subsequent ARIs. Results: A total of 3,851 children and 16,337
      ARI episodes were enrolled and recorded, respectively. Samples were collected
      from 24% of all ARI episodes; collection rate at the healthcare facilities was
      95%. Enterovirus D68, rhinovirus species C, and respiratory syncytial virus were
      significantly associated with severe ARIs. The risk for subsequent ARIs was
      significantly enhanced after infections with adenovirus, influenza A virus,
      parainfluenza virus type 4, and rhinovirus species C. Conclusions: This study
      revealed that viral etiology plays a significant role in the severity of the
      present ARI and that viral infection affects the host's susceptibility to
      subsequent ARIs.

PMID- 30189093
TI  - Liberal Acceptance Bias, Momentary Aberrant Salience, and Psychosis: An
      Experimental Experience Sampling Study.
AB  - Cognitive models of psychosis posit that reasoning biases are an important
      mechanism contributing to the formation of psychotic symptoms, in part through
      transforming anomalous experiences of aberrant salience into frank psychotic
      symptoms. This study aimed to investigate the interplay of liberal acceptance
      (LA) bias, which is a specific type of reasoning bias, and momentary aberrant
      salience in the development of paranoid and psychotic experiences in daily life
      in first-episode psychosis patients (FEP), at-risk mental state participants
      (ARMS), and controls. We used a novel experimental Experience Sampling
      Methodology (eESM) task for measuring LA bias (ie, decisions based on low
      probability estimates) and ESM measures of momentary aberrant salience and
      paranoid and psychotic experiences in 51 FEP, 46 ARMS, and 53 controls. We found
      evidence that LA bias was more likely to occur in FEP than in controls. Further,
      LA bias was associated with psychotic and paranoid experiences (all P < .007) and
      modified the association between momentary aberrant salience and psychotic
      experiences (chi2(df) = 7.4(2), P = .025) in ARMS, such that momentary salience
      was associated with more intense psychotic experiences in the presence of LA bias
      in ARMS, but not in FEP and controls. Our findings suggest that LA bias may be
      central for anomalous experiences such as momentary aberrant salience to increase
      intensity of psychotic experiences in at-risk individuals. Further, LA bias
      appears to be more likely to be present, but not directly linked to current
      intensity of psychotic experiences, in treated FEP. Novel eESM tasks open new
      avenues for targeting psychological processes under real-world conditions.

PMID- 30189094
TI  - The challenges of becoming better sex educators for young people and the
      resources needed to get there: findings from focus groups with economically
      disadvantaged ethnic/racial minority parents.
AB  - The benefits of positive parent-adolescent relationships and effective
      communication on sexual risk have been demonstrated among minority parents and
      teenagers. However, there is need for illuminating how structural inequalities,
      such as economic disadvantage and being an ethnic/racial minority, shape parents'
      approaches to adolescent sexuality. Schalet's cultural framework describes White
      middle-income Dutch parents' 'normalization' (i.e. support for self-regulated
      sexuality, healthy relationships and normalization of teenage sexuality) versus
      White middle-income American parents' 'dramatization' (i.e. emphasis on raging
      hormones, battle between the sexes and pushing sex outside the home) of teenage
      sexuality, approaches which she argues contribute to differences in sexual health
      outcomes in the two countries. We adopt Schalet's framework to explore the
      approaches of 182 economically disadvantaged ethnic/racial minority parents
      attending 1 of 15 focus groups across New York State. The results revealed
      parents' dramatization of teenage sexuality, and how fears about their children's
      health and safety combined with a lack of resources and educational tools
      heightened this dramatization process. Yet parents identified communication
      skills and community resources to help them normalize teenage sexuality. The
      findings have the potential to inform policy makers and practitioners working to
      develop programs and policies to bolster parents' role as effective sex educators
      for adolescents.

PMID- 30189095
TI  - Mechanical tachycardia of the slow pathway induced by a percutaneous tricuspid
      valve device.

PMID- 30189096
TI  - Reduced Neural Sensitivity to Social vs Nonsocial Reward in Schizophrenia.
AB  - Background: Human beings find social stimuli rewarding, which is thought to
      facilitate efficient social functioning. Although reward processing has been
      extensively studied in schizophrenia, a few studies have examined neural
      processes specifically involved in social reward processing. This study examined
      neural sensitivity to social and nonsocial rewards in schizophrenia. Methods:
      Twenty-seven patients with schizophrenia and 25 community controls completed a
      One-Armed Bandit Task, an implicit reinforcement learning task, in the scanner.
      There were 2 conditions with an identical trial structure, one with social
      rewards and the other with nonsocial rewards. The data were analyzed using a
      region of interest (ROI) approach, focusing on the ventral striatum, ventromedial
      prefrontal cortex, and anterior cingulate cortex. Results: Across all 3 ROIs,
      patients showed reduced activation for social rewards compared to controls.
      However, the 2 groups showed comparable levels of activation for nonsocial
      rewards. Within the patient group, levels of neural activation in these ROIs
      during the social reward condition were associated with better performance.
      Conclusions: This study found reduced neural sensitivity in patients with
      schizophrenia in key reward-processing regions for social but not for nonsocial
      rewards. These findings suggest a relatively specific social reward-processing
      deficit in schizophrenia during an implicit reinforcement learning task.

PMID- 30189097
TI  - A Novel Surgical Technique for Management of Giant Central Calcified Thoracic
      Disk Herniations: A Dual Corridor Method Involving Tubular
      Transthoracic/Retropleural Approach Followed by a Posterior Transdural
      Diskectomy.

PMID- 30189099
TI  - Leaf economics spectrum in rice: leaf anatomical, biochemical, and physiological
      trait trade-offs.
AB  - The leaf economics spectrum (LES) is an ecophysiological concept describing the
      trade-offs of leaf structural and physiological traits, and has been widely
      investigated on multiple scales. However, the effects of the breeding process on
      the LES in crops, as well as the mechanisms of the trait trade-offs underlying
      the LES, have not been thoroughly elucidated to date. In this study, a dataset
      that included leaf anatomical, biochemical, and functional traits was constructed
      to evaluate the trait covariations and trade-offs in domesticated species, namely
      rice (Oryza species). The slopes and intercepts of the major bivariate
      correlations of the leaf traits in rice were significantly different from the
      global LES dataset (Glopnet), which is based on multiple non-crop species in
      natural ecosystems, although the general patterns were similar. The
      photosynthetic traits responded differently to leaf structural and biochemical
      changes, and mesophyll conductance was the most sensitive to leaf nitrogen (N)
      status. A further analysis revealed that the relative limitation of mesophyll
      conductance declined with leaf N content; however, the limitation of the
      biochemistry increased relative to leaf N content. These findings indicate that
      breeding selection and high-resource agricultural environments lead crops to
      deviate from the leaf trait covariation in wild species, and future breeding to
      increase the photosynthesis of rice should primarily focus on improvement of the
      efficiency of photosynthetic enzymes.

PMID- 30189098
TI  - CRISPR-Cas adaptation in Escherichia coli requires RecBCD helicase but not
      nuclease activity, is independent of homologous recombination, and is antagonized
      by 5' ssDNA exonucleases.
AB  - Prokaryotic adaptive immunity is established against mobile genetic elements
      (MGEs) by 'naive adaptation' when DNA fragments from a newly encountered MGE are
      integrated into CRISPR-Cas systems. In Escherichia coli, DNA integration
      catalyzed by Cas1-Cas2 integrase is well understood in mechanistic and structural
      detail but much less is known about events prior to integration that generate DNA
      for capture by Cas1-Cas2. Naive adaptation in E. coli is thought to depend on the
      DNA helicase-nuclease RecBCD for generating DNA fragments for capture by Cas1
      Cas2. The genetics presented here show that naive adaptation does not require
      RecBCD nuclease activity but that helicase activity may be important. RecA
      loading by RecBCD inhibits adaptation explaining previously observed adaptation
      phenotypes that implicated RecBCD nuclease activity. Genetic analysis of other E.
      coli nucleases and naive adaptation revealed that 5' ssDNA tailed DNA molecules
      promote new spacer acquisition. We show that purified E. coli Cas1-Cas2 complex
      binds to and nicks 5' ssDNA tailed duplexes and propose that E. coli Cas1-Cas2
      nuclease activity on such DNA structures supports naive adaptation.

PMID- 30189100
TI  - Comparison of Six Artificial Diets for Western Corn Rootworm Bioassays and
      Rearing.
AB  - The western corn rootworm, Diabrotica virgifera virgifera LeConte (Coleoptera:
      Chrysomelidae), is considered the most important maize (Zea mays L.) pest in the
      U.S. Corn Belt. Bioassays testing susceptibility to Bacillus thuringiensis
      Berliner (Bt) and other toxins of corn rootworm larvae often rely on artificial
      diet formulations. Successful bioassays on artificial diet for corn rootworm have
      sometimes been challenging because of microbial contamination. Toward the long
      term goal of developing a universal artificial diet for western corn rootworm
      larvae, we compared larval survival, dry weight, and percentage of molt in 10-d
      bioassays from six current diets of which we were aware. In addition, as part of
      longer term rearing efforts, we recorded molting over an extended period of
      development (60 d). Six different artificial diets, including four proprietary
      industry diets (A, B, C, and D), the first published artificial diet for western
      corn rootworm (Pleau), and a new diet (WCRMO-1) were evaluated. Western corn
      rootworm larval survival was above 90% and contamination was 0% on all diets for
      10 d. Diet D resulted in the greatest dry weight and percentage molting when
      compared with the other diets. Although fourth-instar western corn rootworm
      larvae have not been documented previously (only three instars have been
      previously documented), as many as 10% of the larvae from Diet B molted into a
      fourth instar prior to pupating. Overall, significant differences were found
      among artificial diets currently used to screen western corn rootworm. In order
      for data from differing toxins to be compared, a single, reliable and high
      quality western corn rootworm artificial diet should eventually be chosen by
      industry, academia, and the public as a standard for bioassays.

PMID- 30189102
TI  - Corrigendum.

PMID- 30189104
TI  - Effectiveness of body image directed interventions in patients with anorexia
      nervosa: A systematic review.
AB  - OBJECTIVE: Body image (BI) disturbances are one of the core symptoms of anorexia
      nervosa (AN). They have been shown to be associated with depression and anxiety
      at all treatment stages and are a reliable predictor of relapse. Considering the
      importance for the course of AN, direct targeting of BI disturbances is still
      underemphasized in the treatment of patients with AN. METHOD: In this systematic
      review, conducted according to the PRISMA statement, the evidence on BI directed
      interventions in AN is synthesized. RESULTS: N = 11 studies investigating mirror
      exposure, video confrontation, virtual reality body exposure and treatment
      programs were analyzed. No systematic risk of bias within or across studies could
      be identified. The included studies show that BI directed interventions may be
      efficacious in improving BI related outcomes. However, the evidence regarding an
      additional effect of BI interventions added to established treatments for
      patients with AN, is unclear. DISCUSSION: The evidence base on BI interventions
      for patients with AN is scarce. It is not possible to identify types of BI
      intervention that can be seen as the most promising. Advantages of new
      technologies such as virtual reality or a combination of BI interventions with
      techniques for stress reduction are discussed.

PMID- 30189103
TI  - A path to defining excellence in intensive treatment for eating disorders.
AB  - In the United States, the past decade has seen rapid growth in treatment centers
      providing specialty care to patients with eating disorders. Much of this growth
      has been in higher levels of care, including hospital-based and residential
      treatment. Despite this expansion, there remains lack of agreement regarding the
      most important components of care, such as staff training or specifics of
      treatment delivery. Additionally there is no consensus on how best to assess
      outcome and compare performance across programs. This leaves patients, families,
      public and private insurance programs, and policy makers with limited information
      to help facilitate treatment decisions. The present paper considers implications
      of these changes in the eating disorder treatment landscape and examines two
      ideas that, if implemented, may enhance the quality of eating disorder care.
      First, we explore the proposal to develop a network of centers of excellence in
      eating disorder treatment and the value this may have for improving overall
      treatment quality. This idea was discussed at an expert meeting held at SAMSHA in
      2017 regarding issues important to the field following passage of the 21st
      Century Cures Act. Second, we consider the potential utility of a study using the
      Delphi method to promote expert consensus regarding clinical outcome assessments.

PMID- 30189105
TI  - Solid-State NMR Spectroscopy: A Powerful Technique to Directly Study Small Gas
      Molecules Adsorbed in Metal-Organic Frameworks.
AB  - Metal-organic frameworks (MOFs) have shown great potential in gas separation and
      storage, and the design of MOFs for these purposes is an on-going field of
      research. Solid-state nuclear magnetic resonance (SSNMR) spectroscopy is a
      valuable technique for characterizing these functional materials. It can provide
      a wide range of structural and motional insights that are complementary to and/or
      difficult to access with alternative methods. In this Concept article, the recent
      advances made in SSNMR investigations of small gas molecules (i.e., carbon
      dioxide, carbon monoxide, hydrogen gas and light hydrocarbons) adsorbed in MOFs
      are discussed. These studies demonstrate the breadth of information that can be
      obtained by SSNMR spectroscopy, such as the number and location of guest
      adsorption sites, host-guest binding strengths and guest mobility. The knowledge
      acquired from these experiments yields a powerful tool for progress in MOF
      development.

PMID- 30189101
TI  - Developmental and cancer-associated plasticity of DNA replication preferentially
      targets GC-poor, lowly expressed and late-replicating regions.
AB  - The spatiotemporal program of metazoan DNA replication is regulated during
      development and altered in cancers. We have generated novel OK-seq, Repli-seq and
      RNA-seq data to compare the DNA replication and gene expression programs of
      twelve cancer and non-cancer human cell types. Changes in replication fork
      directionality (RFD) determined by OK-seq are widespread but more frequent within
      GC-poor isochores and largely disconnected from transcription changes. Cancer
      cell RFD profiles cluster with non-cancer cells of similar developmental origin
      but not with different cancer types. Importantly, recurrent RFD changes are
      detected in specific tumour progression pathways. Using a model for establishment
      and early progression of chronic myeloid leukemia (CML), we identify 1027
      replication initiation zones (IZs) that progressively change efficiency during
      long-term expression of the BCR-ABL1 oncogene, being twice more often
      downregulated than upregulated. Prolonged expression of BCR-ABL1 results in
      targeting of new IZs and accentuation of previous efficiency changes. Targeted
      IZs are predominantly located in GC-poor, late replicating gene deserts and
      frequently silenced in late CML. Prolonged expression of BCR-ABL1 results in
      massive deletion of GC-poor, late replicating DNA sequences enriched in origin
      silencing events. We conclude that BCR-ABL1 expression progressively affects
      replication and stability of GC-poor, late-replicating regions during CML
      progression.

PMID- 30189106
TI  - A pilot open trial of UNITE-BED: A couple-based intervention for binge-eating
      disorder.
AB  - OBJECTIVE: To evaluate the feasibility, acceptability, and preliminary efficacy
      of a couple-based intervention for binge-eating disorder (BED), called UNiting
      couples In the Treatment of Eating disorders-BED edition (UNITE-BED). METHOD: In
      an open pilot trial, 11 couples in which one or both adult partners had a
      diagnosis of DSM-5 threshold or sub-threshold BED participated in 22 weekly
      sessions of UNITE-BED. Patients also received individual treatment, outside of
      the context of the trial. Couples completed measures on treatment satisfaction,
      eating disorder symptom severity, depression, anxiety, emotion regulation, and
      relational functioning at post-treatment and 3-month follow-up. Statistical
      analyses were conducted to identify change over the course of treatment. RESULTS:
      UNITE was feasible and acceptable to the majority of couples (9% dropout; high
      satisfaction ratings). Objective binge abstinence was 81.8% and subjective binge
      abstinence was 45.5% by post-treatment. Patient binge-eating symptomatology
      reduced over the course of treatment with results maintained at follow up.
      Patients' depression symptoms decreased and patients' emotion regulation improved
      at both time points. DISCUSSION: Including partners in treatment for BED may be
      beneficial. Results support further evaluation of the efficacy of couple-based
      interventions for BED in larger randomized-controlled trials.

PMID- 30189107
TI  - PTPH1 immunohistochemical expression and promoter methylation in breast cancer
      patients from India: A retrospective study.
AB  - Protein Tyrosine Phosphatase H1/Protein Tyrosine Phosphatase Non receptor Type 3
      (PTPH1/PTPN3) is upregulated and/or mutated in glioma, ovarian, gastric, and
      colorectal cancers. Previous studies have documented that PTPH1-associated breast
      cancers exhibit enhanced sensitivity to tamoxifen and tyrosine kinase inhibitors
      through dephosphorylation of ER and epidermal growth factor receptor,
      respectively. Owing to the key role that PTPH1 plays as a biomarker in predicting
      the response of chemotherapeutic drugs and lack of studies on Indian breast
      cancer patients, the present study investigated PTPH1 protein expression and its
      relationship to clinical features, ER/PR/HER2/neu statuses, and methylation of
      promoter in breast cancer tissues (n = 67) among Indian population by
      immunohistochemistry and methylation specific polymerase chain reaction. PTPH1
      expression was upregulated in 58.21% (39/67) and downregulated in the rest of
      tumor specimens, and it correlated with ER, PR, and HER2/neu statuses with p
      values of <0.0001, 0.0113, and 0.0448, respectively. Additionally, we found that
      the 2 kb region upstream of PTPH1 gene harbored CpG sites within, and was
      ubiquitously methylated in breast cancer (n = 13), colon cancer tissue (n = 1),
      uterine cancer tissue (n = 1), normal breast tissue (n = 1) in addition to Hela
      and MCF7 cell lines. In conclusion, our data showed a strong correlation of the
      PTPH1 status with the ER and ubiquitous nature of PTPH1 promoter methylation at
      specific CpG sites irrespective of cancer types and protein expression. Our
      findings underscore the clinical relevance of PTPH1 expression in Indian patients
      and warrant additional studies to explore the importance of ubiquitously
      methylated promoter at specific CpG sites in upstream of the PTPH1 gene.

PMID- 30189108
TI  - Impact of eating disorders on obstetric outcomes in a large clinical sample: A
      comparison with the HUNT study.
AB  - OBJECTIVE: Current evidence from clinical studies suggests that having an active
      eating disorder (ED) during pregnancy is associated with unfavorable obstetric
      outcomes. However, the role of a lifetime diagnosis of ED is not fully
      understood. Variations in findings suggest a need for additional studies of
      maternal ED. This study aims to identify associations between a lifetime ED and
      obstetric outcomes. METHOD: Data from a hospital patient register and a
      population-based study (The HUNT Study) were linked to the Medical Birth Registry
      in Norway. Register based information of obstetric complications (preeclampsia,
      preterm birth, perinatal deaths, small for gestational age (SGA), large for
      gestational age (LGA), Caesarean sections, and 5-min Apgar score) were acquired
      for 532 births of women with ED and 43,657 births of non-ED women. Multivariable
      regression in generalized estimating equations was used to account for clusters
      within women as they contributed multiple births to the dataset. RESULTS: After
      adjusting for parity, maternal age, marital status, and year of delivery,
      lifetime history of anorexia nervosa was associated with increased odds of having
      offspring who were SGA (Odds ratio (OR) 2.7, 95% Confidence Interval (CI) 1.4
      5.2). Women with a lifetime history of bulimia nervosa had higher odds of having
      a Caesarian section (OR 1.7 95% CI 1.1-2.5). Women with EDNOS/sub-threshold ED
      had a higher likelihood of having a low Apgar score at 5 min (OR 3.1, 95% CI 1.1
      8.8). CONCLUSION: Our study corroborates available evidence on the associations
      between maternal ED and adverse obstetric outcomes.

PMID- 30189110
TI  - Expression of Concern Regarding "Effect of Deconditioning on Cortical and
      Cancellous Bone Growth in the Exercise Trained Young Rats".

PMID- 30189109
TI  - Visually guided TEE probe insertion, making a case based on anatomic variation: A
      cadaveric study.
AB  - AIMS: The variations in upper esophageal anatomy currently are unknown. This
      study was carried out to evaluate this variation and assess its impact on
      transesophageal echocardiography probe insertion. METHODS: We included 9
      consecutive cadavers studied at the University of Maryland School of Medicine's
      Clinical Surgical Laboratory. Each cadaver was first intubated blindly by an
      echocardiographer (KAA) and then under direct vision with a UE Medical VL 400
      video laryngoscope (Newton, MA) by an anesthesiologist (JD). RESULTS: The
      visually guided method took a shorter average time (19.4 +/- 13.4 seconds) and
      fewer passes (2.4 +/- 2.1 passes) than blind insertion (30.3 +/- 19.1 seconds,
      5.3 +/- 3.3 passes). None of the cadavers had the esophagus located directly
      posterior to the trachea. The esophageal hiatus was posterior and to the right of
      the trachea in most (n = 6); in these, the traditional "forward" jaw thrust
      helped to open the esophageal hiatus. Two cadavers had the esophagus and trachea
      located almost side by side, and in these the "forward" jaw thrust method failed.
      Instead, the jaw needed to be pulled to the left in order to advance the probe.
      CONCLUSION: This is the first study to describe anatomic variations in the
      location of and relationship between the upper esophageal sphincter and the
      larynx for the purpose of transesophageal echocardiography probe insertion.
      Awareness of the side-by-side anatomic variation can help to improve esophageal
      intubation by prompting the use of a new "pull to the side" technique instead of
      the traditional "forward" jaw thrust.

PMID- 30189111
TI  - Age Dependence of Systemic Bone Loss and Recovery Following Femur Fracture in
      Mice.
AB  - The most reliable predictor of future fracture risk is a previous fracture of any
      kind. The etiology of this increased fracture risk is not fully known, but it is
      possible that fracture initiates systemic bone loss, leading to greater fracture
      risk at all skeletal sites. In this study, we investigated systemic bone loss and
      recovery after femoral fracture in young (3-month-old) and middle-aged (12-month
      old) mice. Transverse femur fractures were created using a controlled impact, and
      whole-body bone mineral density (BMD), trabecular and cortical microstructure,
      bone mechanical properties, bone formation and resorption rates, mouse voluntary
      movement, and systemic inflammation were quantified at multiple time points post
      fracture. We found that fracture led to decreased whole-body BMD in both young
      and middle-aged mice 2 weeks post-fracture; this bone loss was recovered by 6
      weeks in young but not middle-aged mice. Similarly, trabecular bone volume
      fraction (BV/TV) of the L5 vertebral body was significantly reduced in fractured
      mice relative to control mice 2 weeks post-fracture (-11% for young mice, -18%
      for middle-aged mice); no significant differences were observed 6 weeks post
      fracture. At 3 days post-fracture, we observed significant increases in serum
      levels of interleukin-6 and significant decreases in voluntary movement in
      fractured mice compared with control mice, with considerably greater changes in
      middle-aged mice than in young mice. At this time point, we also observed
      increased osteoclast number on L5 vertebral body trabecular bone of fractured
      mice compared with control mice. These data show that systemic bone loss occurs
      after fracture in both young and middle-aged mice, and recovery from this bone
      loss may vary with age. This systemic response could contribute to increased
      future fracture risk after fracture; these data may inform clinical treatment of
      fractures with respect to improving long-term skeletal health. (c) 2018 American
      Society for Bone and Mineral Research.

PMID- 30189112
TI  - Modification of silicone elastomers with Bioglass 45S5(r) increases in ovo tissue
      biointegration.
AB  - Silicone is an important material family used for various medical implants. It is
      biocompatible, but its bioinertness prevents cell attachment, and thus tissue
      biointegration of silicone implants. This often results in constrictive fibrosis
      and implant failure. Bioglass 45S5(r) (BG) could be a suitable material to alter
      the properties of silicone, render it bioactive and improve tissue integration.
      Therefore, BG micro- or nanoparticles were blended into medical-grade silicone
      and 2D as well as 3D structures of the resulting composites were analyzed in ovo
      by a chick chorioallantoic membrane (CAM) assay. The biomechanical properties of
      the composites were measured and the bioactivity of the composites was verified
      in simulated body fluid. The bioactivity of BG-containing composites was
      confirmed visually by the formation of hydroxyapatite through scanning electron
      microscopy as well as by infrared spectroscopy. BG stiffens as prepared non
      porous composites by 13% and 36% for micro- and nanocomposites respectively. In
      particular, after implantation for 7 days, the Young's modulus had increased
      significantly from 1.20 +/- 0.01 to 1.57 +/- 0.03 MPa for microcomposites and
      1.44 +/- 0.03 to 1.69 +/- 0.29 MPa to for nanocpmosites. Still, the materials
      remain highly elastic and are comparably soft. The incorporation of BG into
      silicone overcame the bioinertness of the pure polymer. Although the overall
      tissue integration was weak, it was significantly improved for BG-containing
      porous silicones (+72% for microcomposites) and even further enhanced for
      composites containing nanoparticles (+94%). These findings make BG a suitable
      material to improve silicone implant properties. (c) 2018 Wiley Periodicals, Inc.
      J Biomed Mater Res B Part B: Appl Biomater, 2018.

PMID- 30189113
TI  - Severe iodine deficiency from dietary restriction and subsequent iodine excess
      from seaweed snack overuse in an adolescent with disordered eating.
AB  - Individuals with disordered eating commonly exclude salt and animal products from
      their diets, which may predispose them to iodine deficiency even without
      significant weight loss. Overconsumption of dietary supplements and "natural"
      foods are also commonly observed among eating disorder patients. This report
      describes an adolescent female with disordered eating presenting with growth and
      pubertal delay, found to have severe iodine deficiency (urine iodine of 18 mcg/L)
      and abnormal thyroid function resulting from strict avoidance of salt and animal
      products despite adequate caloric intake. To avoid having to start eating animal
      products, she began consuming excessive quantities of seaweed supplements to
      increase her iodine intake resulting in excessive iodine levels (urine iodine of
      >1,500 mcg/L) and worsening of thyroid function. When her parents began
      supervising her nutritional intake, her abnormal iodine levels, abnormal thyroid
      function tests, and hypogonadotropic hypogonadism all resolved. This is the first
      report of both iodine deficiency and iodine excess developing from disordered
      eating behavior.

PMID- 30189114
TI  - Rigor, reproducibility, and novel methodological approaches to eating disorders
      research.
AB  - The explosion of new methods in science has put additional pressure on authors,
      readers, and peer reviewers to evaluate the rigor and reproducibility of these
      new approaches. This issue brings together a collection of articles aimed to
      stimulate our thinking about how to evaluate the quality of these new
      methodologies, in the form of several expert reviews on domains ranging from
      large scale genetics to clinical interventions. These expert reviews are followed
      by a collection of papers intended to illustrate new or underrepresented methods
      in our field and include novel approaches to clinical trials to the
      quantification of text data collected from public repositories online. The issue
      concludes with a number of original data papers applying network analysis to
      study comorbidity and symptom status in eating disorder and related populations
      and a couple of novel neuroimaging papers demonstrating the use of new and
      promising methods for studying heterogeneity and the use of psychophysiology to
      answer questions about emotion in eating disorder populations.

PMID- 30189115
TI  - Effects of deep breathing in patients with bipolar disorder.
AB  - PURPOSE: Our aim was to evaluate the effects of deep breathing exercises in
      subjects with bipolar disorder. DESIGN AND METHODS: This was an open-label,
      uncontrolled clinical trial with three assessments: preintervention,
      postintervention, and follow-up. FINDINGS: The Hamilton Anxiety Rating Scale,
      BECK-A, Hamilton Depression Rating Scale, and Young Mania Rating Scale had
      significant preintervention, postintervention, and follow-up differences. The
      results indicated that the deep breathing protocol was effective in reducing
      anxiety levels in patients with bipolar disorder. The deep breathing protocol has
      no negative side effects and might be applied to decrease anxiety symptoms in
      individuals with bipolar disorder. PRACTICE IMPLICATIONS: The results provide
      direction for providing quality care that reduces anxiety levels in patients with
      bipolar disorder.

PMID- 30189116
TI  - Improving motivation to change amongst individuals with eating disorders: A
      systematic review.
AB  - OBJECTIVE: People with eating disorders can have low motivation to change their
      eating disorder behaviors. Interventions aiming to enhance motivation to change
      have been increasingly advocated in their treatment. Questions remain regarding
      the strength of the evidence supporting the effectiveness of interventions that
      specifically focus on improving motivation. This review explored the evidence for
      improving motivation to change in eating disorders via clinical interventions.
      METHOD: Searches of the published and unpublished literature were conducted by
      searching databases (PubMed, PsychInfo, Web of Science) and trial registries (WHO
      ICTRP), and by contacting authors. Studies were included if they investigated an
      intervention for eating disorder patients, included a pre-post outcome measure of
      motivation to change and were published in English. Risk of bias was also
      assessed. RESULTS: Forty-two studies were included in the final review. Evidence
      was found to support the use of interventions to improve motivation to change,
      though it was unclear whether motivational interventions present a more effective
      option than approaches that do not exclusively or specifically focus on
      motivation. However, motivational interventions were identified as being more
      effective than low intensity treatments. Risk of bias in included studies was
      generally high. DISCUSSION: Motivation was found to increase across treatments in
      general, whether or not the focus of the intervention was on enhancing
      motivation. It is unclear if interventions specifically targeting motivation to
      change provide additional benefit over and above established treatment
      approaches.

PMID- 30189118
TI  - Multiple Halogenation of Aliphatic C-H Bonds within the Hofmann-Loffler Manifold.
AB  - An innovative approach to position-selective polyhalogenation of aliphatic
      hydrocarbon bonds is presented. The reaction proceeded within the Hofmann-Loffler
      manifold with amidyl radicals as the sole mediators to induce selective 1,5- and
      1,6-hydrogen-atom transfer followed by halogenation. Multiple halogenation events
      of up to four innate C-H bond functionalizations were accomplished. The broad
      applicability of this new entry into polyhalogenation and the resulting synthetic
      possibilities were demonstrated for a total of 27 different examples including
      mixed halogenations.

PMID- 30189117
TI  - Trends in breast cancer mortality by stage at diagnosis among young women in the
      United States.
AB  - BACKGROUND: Assessing trends in breast cancer survival among young women who are
      largely unaffected by breast cancer screening will provide important information
      regarding improvements in the effectiveness of cancer care for breast cancer in
      the last few decades. METHODS: The cohort for this study consisted of women who
      were diagnosed with breast cancer between ages 20 and 39 years from the
      Surveillance, Epidemiology, and End Results program's 9-registry areas from 1975
      to 2015. Trends in the breast cancer incidence rate and survival were assessed
      among young women. RESULTS: Among women aged 20 to 39 years, breast cancer
      incidence increased from 24.6 per 100,000 in 1975 to 31.7 per 100,000 in 2015
      (annual percent change, 0.5; 95% confidence interval [CI], 0.4-0.6). Among women
      with breast cancer, 5-year breast-cancer-specific survival increased
      significantly from 74.0% during 1975 to 1979 to 88.5% during 2010 to 2015 (hazard
      ratio for dying from breast cancer for 2010-2015 vs 1975-1979, 0.37; 95% CI, 0.32
      0.41). The increase in cancer-specific survival reached a plateau in 2005;
      however, among young women with metastatic breast cancer, it continued to
      increase after 2005, from 45.6% during 2005 to 2009 to 56.5% during 2010 to 2015
      (hazard ratio for dying from breast cancer for 2010-2015 vs 2005-2009, 0.74; 95%
      CI, 0.60-0.92). Similar patterns also were observed for 5-year overall survival
      and among women aged 20 to 29 years and those aged 30 to 39 years. CONCLUSIONS:
      There were substantial improvements in the effectiveness of breast cancer
      treatment on overall and cancer-specific survival from 1975 to 2015. However,
      improvements appeared to have reached a plateau after 2005, except among young
      women with metastatic breast cancer, in whom survival continued to improve
      throughout the period.

PMID- 30189119
TI  - Roles of positive psychological outcomes in future health perception and mental
      health problems: A report from the Childhood Cancer Survivor Study.
AB  - OBJECTIVE: Positive psychological outcomes among adolescent and young adult
      survivors of childhood cancer may influence long-term health status. We examined
      posttraumatic growth (PTG) and Life satisfaction (LS) in adolescence, and their
      impact on future emotional and physical health status in young adulthood.
      METHODS: Survivors (n = 2802) from the Childhood Cancer Survivor Study were
      longitudinally analyzed across social, emotional, and physical factors during
      adolescence (12-17 years old), and PTG (PTG-Inventory) and LS (Cantril-Ladder-of
      Life) during young adulthood (19-24 years old). The impact of PTG and LS on
      survivors' future long-term mental health, physical health, and social skills was
      also examined (23-28 years old) using Structural Equation Modeling. RESULTS:
      Survivors reported high levels of LS (M = 7.43, range 1 to 10) and a positive
      impact from their cancer experience (M = 48.78, range 0 to 105). Adolescent
      predictors of higher PTG included older age at diagnosis (p = 0.001),
      experiencing more severe chronic health conditions (p = 0.01), cancer
      recurrence/relapse (p = 0.01), and being diagnosed with a non-CNS cancer (p =
      0.001). Higher perceived general health (p = 0.01), higher social skills (p =
      0.001), and diagnosis with a non-CNS cancer (p = 0.02) were associated with
      higher LS. Higher PTG during young adulthood predicted poorer perceived health (p
      = 0.04) and worse emotional health (p = 0.001) in later adulthood. Higher LS
      predicted better emotional health (p = 0.001) and better perceived health (p =
      0.001). CONCLUSIONS: While LS was found to help survivors have better perceived
      long-term emotional and physical health outcomes, survivors with higher PTG fond
      both positive and negative impacts from cancer. Future therapeutic trials to
      improve LS should be considered.

PMID- 30189120
TI  - Another perspective on how visual neuroscience can inform the treatment of
      anorexia nervosa: A response to Feusner et al.

PMID- 30189121
TI  - The effect of maternal metabolic status on offspring health: a role for skeletal
      muscle?

PMID- 30189122
TI  - The influence of gender on the evaluation of anorexia nervosa.
AB  - A stereotype exists that anorexia nervosa (AN) is a "female" disorder. As a
      result, men with AN may face harsher stigmatization from their peers or go
      undiagnosed. The shifting standards model provides a framework to explore how
      gender stereotypes impact perceptions of AN. Participants (N = 438) were given a
      vignette of a person with symptoms of AN labeled as either male or female.
      Assessments were experimentally manipulated according to the shifting standards
      perspective: participants were asked if they were concerned (or convinced) that
      the target had AN and then indicated the severity of behavioral symptoms (calorie
      reduction, pounds lost per week, and hours of exercise) needed to make them
      concerned (or convinced) of AN. Participants were more likely to state that the
      male target had AN compared to the female target (p = .036) whereas women were
      more likely to believe an individual had AN than men, regardless of the target
      gender (p < .001). In addition, men required that the male target have more
      severe symptoms to assign an AN diagnosis than women (p = .005). In general,
      severity ratings for symptoms were quite high, indicating a normalization of
      unhealthy weight loss practices. These results confirm that gender affects the
      perception of AN, though they do not conform to expectations within the shifting
      standards model. Instead, they suggest that a male target is more readily
      identified as having AN than a female target with AN when exhibiting identical
      symptoms.

PMID- 30189123
TI  - Brief spiritual well-being screening is nonlinearly related to psychological
      distress in ambulatory cancer patients.

PMID- 30189124
TI  - [EFFECT OF PROBIOTIC ENTEROCOCCI AND GLATIRAMER ACETATE ON THE SEVERITY OF
      EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS IN RATS ].
AB  - Currently intestinal microbiota is considered as a potential target for influence
      in various pathologies which have inflammation, autoimmunity or neurodegeneration
      in the genesis. Multiple sclerosis (MS) combines all these processes in the
      pathogenesis. Furthermore, the balance of the components of intestinal microbiota
      is disrupted during MS and followed by disbiosis. Different probiotics - bacteria
      with proven beneficial properties are widely used to correct dysbisis. In this
      paper, was investigated the ability of probiotic strain Enterococcus faecium L-3
      to reduce disease severity in multiple sclerosis model - experimental allergic
      encephalomyelitis (EAE). E. faecium L-3 were used alone or in combination with
      glatiramer acetate (GA). It is shown that administration of E. faecium L-3
      reduces the severity of EAE in rats almost as same as that of GA. However, when
      the probiotic enterococci administered together with GA the protective effect
      does not observed. It is assumed that these preparations stimulates different
      ways of the immune system, because their action stimulate different immune cells
      populations. The study demonstrates the ability of E. faecium L-3 to influence on
      the immune system in MS, directly and indirectly (through the correction of
      dysbiosis). This fact allows us to consider E. faecium L-3 as a potential tool
      for immunomodulation in autoimmune, inflammatory and neurodegenerative diseases.

PMID- 30189125
TI  - [THE PARTICIPATION OF THE ELEMENTS OF CYTOSKELETON IN THE MOBILIZATION OF Ca2+
      FROM INTRACELLULAR STORES OF INTACT AND DEVITRIFIED PORCINE OOCYTES].
AB  - Joint action of theophylline and guanosine diphosphate leads to the additional
      release of Ca2+ from intracellular stores of oocytes with intact microfilaments
      and microtubules, additional release of Ca2+ was not observed in oocytes after
      the joint action of prolactin and guanosine triphosphate. In the presence of an
      inhibitor of polymerization microfilaments cytochalasin D additional release of
      Ca2+ not detected in oocytes treated by theophylline and guanosine diphosphate,
      but treatment of oocyte by prolactin with guanosine triphosphate leads to the
      additional release of Ca2+ from intracellular stores. Nocodazole had no effect on
      the release of Ca2+ from intracellular stores of oocytes treated by theophylline
      with guanosine diphosphate or prolactin with guanosine triphosphate. The joint
      action of prolactin and guanosine triphosphate on devitrified oocytes with
      destroyed microfilaments (as a result of defrosting) leads to additional Ca2+
      exit from the intracellular stores. The obtained data expand ideas concerning
      features of regulation of intracellular processes in porcine oocytes.

PMID- 30189126
TI  - [ENGAGEMENT OF SEROTONIN-MODULATING ANTICONSOLIDATION PROTEIN IN REGULATION OF
      EMBRYOGENESIS OF LYMNEAE STAGNALIS AND LEWIS SARCOMA IN HYBRID MICE Fl C57B2/6 X
      DBA].
AB  - The article concerns study of the effects of a novel serotonin-modulating
      anticonsolidation protein (SMAP) being in a linear relationship with serotonin
      level, on embryogenesis of Lymneae stagnalis and Lewis sarcoma in hybrid mice Fl
      C57B2/6 X DBA. Inhibition of embryogenesis of Lymneae stagnalis on the stage of
      four blastomers and late blastula, lack of changes on the stage of trochofora and
      acceleration of metamorphosis under the effects of SMAP in a dose-dependent
      manner was observed. Short-term retardation (during the first 10 days) of
      development of Lewis sarcoma in mice and survival of 25% of transferring animals
      under high doses of SMAP was revealed. Cytostatic activity for high doses of SMAP
      and their effects on the duration of single phases of the cell cycle is proposed.

PMID- 30189127
TI  - [THE CARDIORESPIRATORY PLASTICITY IN CHILDREN DURING THE PROCEDURE OF PACED
      BREATHING].
AB  - The cardiorespiratory plasticity in healthy children 9-10 years old (n = 72) was
      studied during the procedure of paced breathing. The observations of a child
      after an informed consent taken from him, his parents and teachers were carried
      out by a psychologist, a physiologist and a doctor after the lessons. In a
      preliminary series 1 minute trials of pace breathing with various frequencies (22
      5.5 times/minute) were used which showed a good endurance of slow breathing.
      Inthemain series a 3 minute baseline recording and 4-5 periods of 1.5 minute
      duration with a stepwise reduction of breathing rate of 12, 8, 7, 6 times/minute
      and in 10 children - 5.5 times/minute were registered. Computer-aided pacer set
      the durations of inspiration, expiration, pause. The main parameters of heart
      rate variability (HRV) and corresponding FFT spectra were analyzed by ANOVA. In
      children a high cardiorespiratory plasticity of heart rhythm according to
      frequency of pace breathing is observed. During the stepwise reduction of
      breathing rate a quasilinear growth of HRV and peak power of FFT spectra of RR
      intervals are registered, reaching the maximum level in a HF-band at 12
      breaths/min and in LF-band at frequencies of 6-5.5 that are critical to the
      sustained volitional control of cardiorespiratory processing in children. At 6
      5.5 breaths/min a growth of HF-band power of heart rhythm modulation is also
      registered.

PMID- 30189128
TI  - Harnessing the Noncovalent Interactions of DNA Backbone with 2D Silicate
      Nanodisks To Fabricate Injectable Therapeutic Hydrogels.
AB  - Injectable hydrogels present several advantages over prefabricated scaffolds
      including ease of delivery, shear-thinning property, and broad applicability in
      the fields of drug delivery and tissue engineering. Here, we report an approach
      to develop injectable hydrogels with sustained drug release properties,
      exploiting the chemical nature of the DNA backbone and silicate nanodisks. A two
      step gelation method is implemented for generating a combination of noncovalent
      network points, leading to a physically cross-linked hydrogel. The first step
      initiates the development of an interconnected structure by utilizing DNA
      denaturation and rehybridization mechanism to form hydrogen bonds between
      complementary base pairs of neighboring DNA strands. The anisotropic charge
      distribution of two-dimensional silicate nanodisks (nSi) makes them an active
      center in the second step of the gelation process. Silicate nanodisks create
      additional network points via attractive electrostatic interactions with the DNA
      backbone, thereby enhancing the mechanical resilience of the formulated hydrogel.
      The thermally stable hydrogels displayed an increase in elasticity and yield
      stress as a function of nSi concentration. They were able to form self-supporting
      structures post injection due to their rapid recovery after removal of cyclic
      stress. Moreover, the presence of nanosilicate was shown to modulate the release
      of a model osteogenic drug dexamethasone (Dex). The bioactivity of released Dex
      was confirmed from in vitro osteogenic differentiation of human adipose stem
      cells and in vivo bone formation in a rat cranial bone defect model. Overall, our
      DNA-based nanocomposite hydrogel obtained from a combination of noncovalent
      network points can serve as an injectable material for bone regeneration and
      carrier for sustained release of therapeutics.

PMID- 30189129
TI  - Design of Highly Water-Resistant, Impermeable, and Flexible Thin-Film
      Encapsulation Based on Inorganic/Organic Hybrid Layers.
AB  - The lack of a transparent, flexible, and reliable encapsulation layer for organic
      based devices makes it difficult to commercialize wearable, transparent, flexible
      displays. The reliability of organic-based devices sensitive to water vapor and
      oxygen must be guaranteed through an additional encapsulation layer for the
      luminance efficiency and lifetime. Especially, one of the major difficulties in
      current and future OLED applications has been the absence of thin-film
      encapsulation with superior barrier performance, mechanical flexibility, and
      water-resistant properties. In this work, we fabricated highly water-resistant,
      impermeable, and flexible inorganic/organic multilayers with optimized Al2O3 and
      functional organic layers. The key properties of the fabricated multilayers were
      compared according to the thickness and functionality of the inorganic and
      organic layers. Improvement of the barrier performance is mainly attributed to
      the optimized thickness of the Al2O3 films, and is additionally due to the
      increased lag time and effective surface planarization effects caused by the use
      of micrometer-thick organic layers. As a result, the 3-dyad multilayer structure
      composed of 60-nm-thick Al2O3 layers deposited at 70  degrees C and 2-MUm-thick
      silane-based inorganic/organic hybrid polymer (silamer) layers with layered
      silica exhibited the lowest WVTR value of 1.11 * 10-6 g/m2/day in storage
      conditions of 30 degrees C/90% relative humidity. In addition, the multi-barrier
      exhibited good mechanical stability through the use of alternating stacks of
      brittle inorganic and soft organic layers, without showing a large increase in
      the WVTR after bending tests. In addition, silamer layers improved the
      environmental stability of the Al2O3 ALD film. The silamer layer coated on the
      Al2O3 film effectively worked as a protective layer against harsh environments.
      The effective contact at the interface of Al2O3/silamer makes the barrier
      structure more impermeable and corrosion-resistant. In this study, we not only
      demonstrated an optimized multilayer based on functional organic layers, but also
      provided a methodology for designing a wearable encapsulation applicable to
      wearable organic electronics.

PMID- 30189130
TI  - Competition-Enhanced Ligand Selection to Identify DNA Aptamers.
AB  - Competition-enhanced ligand screening (CompELS) was employed to rapidly screen
      through large DNA libraries to identify single-stranded, oligonucleotide-based
      ligands called aptamers that bind to a nonbiological target. This previously
      unreported aptamer screening approach involves the repeated introduction of
      unenriched random sequence populations during the biopanning process, but avoids
      iterative elution and polymerase chain reaction (PCR) amplification steps
      inherent to traditional SELEX (systematic evolution of ligands by exponential
      enrichment) screening. In this study, 25 aptamers were identified against a gold
      surface via CompELS and evaluated to identify patterns in primary structures and
      predicted secondary structures. Following a final one-round competition
      experiment with the 25 identified aptamers, one particular aptamer sequence (1N)
      emerged as the most competitive adsorbate species for the gold substrate. Binding
      analysis indicated at least an order of magnitude difference in the binding
      affinity of 1N ( Kd = 5.6 * 10-10 M) compared to five other high affinity aptamer
      candidates ( Kd = 10-8-10-9 M) from identical secondary structure families.
      Collectively, these studies introduce a rapid, reliable screening and ranking
      platform along with a classification scheme well-suited for identifying and
      characterizing aptamers for nonbiological as well as biological targets.

PMID- 30189131
TI  - Comprehensive Analysis of the Neglect of Diatomic Differential Overlap
      Approximation.
AB  - Many modern semiempirical molecular orbital models are built on the neglect of
      diatomic differential overlap (NDDO) approximation. An in-depth understanding of
      this approximation is therefore indispensable to rationalize the success of these
      semiempirical molecular orbital models and to develop further improvements on
      them. The NDDO approximation provides a recipe to approximate electron-electron
      repulsion integrals (ERIs) in a symmetrically orthogonalized basis based on a far
      smaller number of ERIs in a locally orthogonalized basis. We first analyze the
      NDDO approximation by comparing ERIs in both bases for a selection of molecules
      and for a selection of basis sets. We find that the errors in Hartree-Fock and
      second-order Moller-Plesset perturbation theory energies grow roughly linearly
      with the number of basis functions. We then examine different approaches to
      correct for the errors caused by the NDDO approximation and propose a strategy to
      directly correct for them in the two-electron matrices that enter the Fock
      operator.

PMID- 30189132
TI  - Characteristic Regions of the Fluorescence Excitation-Emission Matrix (EEM) To
      Identify Hydrophobic/Hydrophilic Contents of Organic Matter in Membrane
      Bioreactors.
AB  - This study systematically investigated the correlations between fluorescence
      distributions characterized by the excitation-emission matrix (EEM) and
      hydrophobic/hydrophilic composition of dissolved organic matter (DOM) in membrane
      bioreactors (MBRs). On the basis of samples from 10 full-scale MBRs, we performed
      point-to-point comparisons among different components using an EEM fluorescence
      quotient (FQ) method and obtained a hydrophobic/hydrophilic fluorophore
      distribution map via Wilcoxon signed rank test. Hydrophobic acids/bases (HOA/HOB)
      concentrated in the low-wavelength region [excitation wavelength (Ex) < 235 nm],
      while hydrophilic substances (HIS) were enriched in the region of Ex > 235 nm
      [especially with emission wavelength (Em) = 300-360 nm]. Quantitatively, EEM
      regional contribution to whole wavelength fluorescence was found to significantly
      correlate with the hydrophobic/hydrophilic proportions of DOM, with Pearson's
      coefficients of 0.94 and 0.78 ( p < 0.01) for HOA and HIS, respectively. We
      established a linear regression model showing the HOA proportion as a function of
      the EEM regional contribution at (Ex, Em) = (200-285, 340-465 nm), with R2 =
      0.876, which was validated via leave-one-out cross-validation and Monte Carlo
      simulation. This study shows a statistically hydrophobicity-dependent
      fluorescence property across different MBRs, and it might be applied to provide a
      quick estimation of hydrophobic/hydrophilic composition of DOM in wastewater
      treatment systems based on EEM monitoring.

PMID- 30189133
TI  - Antioxidant Activity of Hydrogen Nanobubbles in Water with Different Reactive
      Oxygen Species both in Vivo and in Vitro.
AB  - Hydrogen water as a new therapeutic antioxidant has been widely used in living
      organisms under stress. In this study, we applied nanobubble (NB) technology to
      hydrogen water. The antioxidant capacity of hydrogen NB water was studied with
      respect to different reactive oxygen species (ROS) both in vitro and in vivo.
      Using a relatively weak reduced dye, APF, we showed that hydrogen NB water can
      effectively remove three cytotoxic ROS, *OH, ClO-, and ONOO-, from water.
      Hydrogen NB water could also remove O2*-, which is a physiologically important
      ROS, from water. However, hydrogen water could not reduce other physiologically
      important ROS such as H2O2 and NO. At similar dissolved hydrogen concentrations,
      hydrogen NB water displayed higher antioxidant activity than hydrogen water
      without NB. Barley seed germination tests were used to study the antioxidant
      effect of hydrogen NB water on ROS generation in vivo. Our results showed that
      this decreased the physiological activity of barley seeds in their normal
      homeostatic state. Hydrogen NB water eliminated endogenous O2*- in seeds and
      inhibited germination. The usage of hydrogen NB water should be individually
      considered according to the types of cells involved. Our results offer basic data
      concerning the application of hydrogen NB water in different fields.

PMID- 30189134
TI  - Utilization of Resist Stencil Lithography for Multidimensional Fabrication on a
      Curved Surface.
AB  - The limited ability to fabricate nanostructures on nonplanar rugged surfaces has
      severely hampered the applicability of many emerging technologies. Here we report
      a resist stencil lithography based approach for in situ fabrication of
      multidimensional nanostructures on both planar and uneven substrates. By using
      the resist film as a flexible stencil to form a suspending membrane with
      predesigned patterns, a variety of nanostructures have been fabricated on curved
      or uneven substrates of diverse morphologies on demand. The ability to realize 4
      in. wafer scale fabrication of nanostructures as well as line width resolution of
      sub-20 nm is also demonstrated. Its extraordinary capacity is highlighted by the
      fabrication of three-dimensional wavy nanostructures with diversified cell
      morphologies on substrates of different curvatures. A robust general scheme is
      also developed to construct various complex 3D nanostructures. The use of
      conventional resists and processing ensures the versatility of the method. Such
      an in situ lithography technique has offered exciting possibilities to construct
      nanostructures with high dimensionalities that can otherwise not be achieved with
      existing nanofabrication methods.

PMID- 30189135
TI  - Reactivity of Electronically Excited SO2 with Alkanes.
AB  - We studied the reaction of electronically excited sulfur dioxide in the triplet
      state (3SO2) with a variety of alkane species, including propane, n-butane,
      isobutane, n-pentane, n-hexane, cyclohexane, n-octane, and n-nonane. Reaction
      rate constants for the photoinitiated reaction of SO2 with all of these species
      were determined and found to be in the range from 3.7 * 10-13 to 5.1 * 10-12
      cm3molecule-1s-1. We found that reaction proceeds via a hydrogen abstraction to
      form HOSO* and organic radical (R*) species and that reactivity is correlated
      with the energy required to break a C-H bond and the length of the alkane chain.
      Abstraction rates were found to be fastest for reaction with hydrogen on a
      tertiary carbon. Similarly, abstraction from secondary carbons is found to be
      faster than from primary carbons. The reactivity of 3SO2 with alkanes increases
      with chain length as additional secondary carbons are added.

PMID- 30189136
TI  - Lowering Lipophilicity by Adding Carbon: One-Carbon Bridges of Morpholines and
      Piperazines.
AB  - In this article, we report our investigation of a phenomenon by which bridging
      morpholines across the ring with one-carbon tethers leads to a counterintuitive
      reduction in lipophilicity. This effect was also found to occur in piperazines
      and piperidines and lowered the measured log D7.4 of the bridged molecules by as
      much as -0.8 relative to their unbridged counterparts. As lowering lipophilicity
      without introducing additional heteroatoms can be desirable, we believe this
      potentially provides a useful tactic to improve the drug-like properties of
      molecules containing morpholine-, piperazine-, and piperidine-like motifs.

PMID- 30189137
TI  - Giant Voltage Enhancement via Triboelectric Charge Supplement Channel for Self
      Powered Electroadhesion.
AB  - Electroadhesion generates an adhesion force using an externally applied power
      source, which has versatile applications in robotics and material handling. In
      this study, a self-powered electroadhesion system using enhanced triboelectric
      nanogenerators (TENGs) to supply power for electroadhesion is presented. By
      introducing a triboelectric charge supplement channel, the open circuit voltage
      of the TENG can be significantly boosted by over 10 times, from ~230 V to more
      than 3300 V for a single TENG unit, providing sufficiently high voltage for an
      electroadhesive patch to generate enough adhesion for practical use. The charge
      supplement channel takes effect through a replenishing mechanism for dissipated
      charges, maintaining an optimal charge distribution throughout TENG electrodes,
      which enables the highest open circuit voltage under given surface charge density
      and device configuration. The fabricated self-powered electroadhesion system
      shows the ability to manipulate objects of various materials via easy and
      straightforward operations, demonstrating a great potential for applications in
      material handling and robotics. Moreover, the voltage enhancement mechanism by
      the charge supplement channel could be extended to TENGs of other modes, which
      can provide reliable power sources for various applications that require a high
      voltage.

PMID- 30189138
TI  - Application of FRET Microscopy to the Study of the Local Environment and Dynamics
      of DNA SAMs on Au Electrodes.
AB  - Immobilized DNA probe strands self-assembled on an electrode surface are the
      bases of many electrochemically based biosensors. Control or measurement of the
      local environment around each DNA molecule tethered to the electrode surface is
      needed because the local environment can influence the binding or hybridization
      efficiency of the target in solution. Measurement of this local environment in
      buffer or under electrochemical control can be challenging. Here we demonstrate
      the use of fluorescence microscopy and a Forster resonance energy transfer (FRET)
      methodology to characterize multicomponent DNA SAMs. The DNA SAMs that were
      studied were composed of a series of mole fraction ratios of alkylthiol-modified
      DNA which was labeled with either AlexaFluor488 or AlexaFluor647, a FRET donor
      and acceptor, respectively. The DNA SAMs were hybridized before assembly onto the
      electrode surface. Wide-field filter-based FRET microscopy was used to study the
      assembly of DNA SAMs onto gold bead electrodes. These single-crystal gold bead
      electrodes contain many surface crystallographic regions which enable the
      comparison of the adsorbed DNA local environment. These surfaces show that most
      surface modifications are uniformly prepared, and the FRET efficiency can be
      explained through simple surface density considerations. The FRET efficiency for
      different compositions of the donor and acceptor for these regions is also
      explained through 2D FRET modeling. Not all surfaces were similar to the (111)
      and (110) regions showing deviations from the expected FRET behavior. Also
      demonstrated is FRET imaging using a confocal microscope. This approach proves
      useful in the analysis of a more dynamic system, such as the analysis of
      reductive desorption of the mixed-component DNA SAM. FRET microscopy is useful
      for surface analysis of the DNA local environment, enabling a measure of the
      surface modification, local density, and clustering and eventually a new
      detection modality.

PMID- 30189139
TI  - Design of Large-Scale Reporter Construct Arrays for Dynamic, Live Cell Systems
      Biology.
AB  - Dynamic systems biology aims to identify the molecular mechanisms governing cell
      fate decisions through the analysis of living cells. Large scale molecular
      information from living cells can be obtained from reporter constructs that
      provide activities for either individual transcription factors or multiple
      factors binding to the full promoter following CRISPR/Cas9 directed insertion of
      luciferase. In this report, we investigated the design criteria to obtain
      reporters that are specific and responsive to transcription factor (TF) binding
      and the integration of TF binding activity with genetic reporter activity. The
      design of TF reporters was investigated for the impact of consensus binding site
      spacing sequence and off-target binding on the reporter sensitivity using a
      library of 25 SMAD3 activity reporters with spacers of random composition and
      length. A spacer was necessary to quantify activity changes after TGFbeta
      stimulation. TF binding site prediction algorithms (BEEML, FIMO and DeepBind)
      were used to predict off-target binding, and nonresponsiveness to a SMAD3
      reporter was correlated with a predicted competitive binding of constitutively
      active p53. The network of activity of the SMAD3 reporter was inferred from
      measurements of TF reporter library, and connected with large-scale genetic
      reporter activity measurements. The integration of TF and genetic reporters
      identified the major hubs directing responses to TGFbeta, and this method
      provided a systems-level algorithm to investigate cell signaling.

PMID- 30189140
TI  - Amyloid Growth, Inhibition, and Real-Time Enzymatic Degradation Revealed with
      Single Conical Nanopore.
AB  - Amyloid fibrils are involved in several neurodegenerative diseases. However,
      because of their polymorphism and low concentration, they are challenging to
      assess in real-time with conventional techniques. Here, we present a new approach
      for the characterization of the intermediates: protofibrils and "end-off"
      aggregates which are produced during the amyloid formation. To do so, we have
      fashioned conical track-etched nanopores that are functionalized to prevent the
      fouling. Using these nanopores, we have followed the kinetic of amyloid growth to
      discriminate the different intermediates protofibrils and "end-off. Then, the
      nanopore was used to characterize the effect of promoter and inhibitor of the
      fibrillation process. Finally, we have followed in real-time the degradation of
      amyloid with peptase. Compare with the SiN nanopore, the track-etched one
      features exceptionally high success rate via functionalization and detection in
      "one-pot". Our results demonstrate the potential for a conical nanopore to be
      used as a routine technique for the characterization of the amyloid growth and/or
      degradation.

PMID- 30189141
TI  - Hierarchical Crystals Formed from DNA-Functionalized Janus Nanoparticles.
AB  - Harnessing anisotropic interactions in a DNA-mediated nanoparticle assembly holds
      great promise as a rational strategy to advance this important area. Here, using
      molecular dynamics simulations, we report the formation of novel hierarchical
      crystalline assemblies of Janus nanoparticles functionalized with two types of
      DNA chains (DNA-JNPs). We find that in addition to the primary nanoparticle
      crystallization into face-centered cubic (FCC) structure, sequence-specific DNA
      hybridization events further direct the rotational orientation of the DNA-JNPs to
      diverse secondary crystalline phases including simple cubic (SC), tetragonally
      ordered cylinder (P4), and lamella (L) structures, which are mapped in the phase
      diagrams relating to various asymmetric parameters. The crystallization dynamics
      of such hierarchical crystals is featured by two consequent processes: entropy
      dominated translational order for the primary crystalline structure and enthalpy
      dominated rotational order for the secondary crystalline structure. For DNA-JNPs
      with high asymmetry in DNA sequence length, tetrahedral nanoclusters tend to be
      favored, which is revealed to be governed by the conformational entropy penalty
      caused by bounded DNA chains. This work might bear important consequences for
      constructing new classes of nanoparticle crystals with designed structures and
      properties at multiple levels and in a predictable manner.

PMID- 30189142
TI  - In Situ Measurement of Electric-Field Screening in Hysteresis-Free
      PTAA/FA0.83Cs0.17Pb(I0.83Br0.17)3/C60 Perovskite Solar Cells Gives an Ion
      Mobility of ~3 * 10-7 cm2/(V s), 2 Orders of Magnitude Faster than Reported for
      Metal-Oxide-Contacted Perovskite Cells with Hysteresis.
AB  - We apply a series of transient measurements to operational perovskite solar cells
      of the architecture ITO/PTAA/FA0.83Cs0.17Pb(I0.83Br0.17)3/C60/BCP/Ag, and similar
      cells with FA0.83MA0.17. The cells show no detectable JV hysteresis. Using
      photocurrent transients at applied bias we find a ~1 ms time scale for the
      electric field screening by mobile ions in these cells. We confirm our
      interpretation of the transient measurements using a drift-diffusion model. Using
      Coulometry during field screening relaxation at short circuit, we determine the
      mobile ion concentration to be ~1 * 1018/cm3. Using a model with one mobile ion
      species, the concentration and the screening time require an ion mobility of ~3 *
      10-7 cm2/(V s). As far as we know, this article gives the first direct
      measurement of the ion mobility and concentration in a fully functional
      perovskite solar cell. The measured ion mobility is 2 orders of magnitude higher
      than the highest estimates previously determined using perovskite solar cells and
      perovskite thin films, and 3 orders of magnitude higher than is frequently used
      in modeling hysteresis effects. We provide evidence that the fast field screening
      is due to mobile ions, as opposed to dark injection and trapping of electronic
      carriers.

PMID- 30189143
TI  - Effect of MnO2 Phase Structure on the Oxidative Reactivity toward Bisphenol A
      Degradation.
AB  - Manganese dioxides (MnO2) are among important environmental oxidants in
      contaminant removal; however, most existing work has only focused on naturally
      abundant MnO2. We herein report the effects of different phase structures of
      synthetic MnO2 on their oxidative activity with regard to contaminant
      degradation. Bisphenol A (BPA), a frequently detected contaminant in the
      environment, was used as a probe compound. A total of eight MnO2 with five
      different phase structures (alpha-, beta-, gamma-, delta-, and lambda-MnO2) were
      successfully synthesized with different methods. The oxidative reactivity of
      MnO2, as quantified by pseudo-first-order rate constants of BPA oxidation,
      followed the order of delta-MnO2-1 > delta-MnO2-2 > alpha-MnO2-1 > alpha-MnO2-2 ~
      gamma-MnO2 > lambda-MnO2 > beta-MnO2-2 > beta-MnO2-1. Extensive characterization
      was then conducted for MnO2 crystal structure, morphology, surface area,
      reduction potential, conductivity, and surface Mn oxidation states and oxygen
      species. The results showed that the MnO2 oxidative reactivity correlated highly
      positively with surface Mn(III) content and negatively with surface Mn average
      oxidation state but correlated poorly with all other properties. This indicates
      that surface Mn(III) played an important role in MnO2 oxidative reactivity. For
      the same MnO2 phase structure synthesized by different methods, higher surface
      area, reduction potential, conductivity, or surface adsorbed oxygen led to higher
      reactivity, suggesting that these properties play a secondary role in the
      reactivity. These findings provide general guidance for designing active MnO2 for
      cost-effective water and wastewater treatment.

PMID- 30189144
TI  - A Comparison of the Bravyi-Kitaev and Jordan-Wigner Transformations for the
      Quantum Simulation of Quantum Chemistry.
AB  - The ability to perform classically intractable electronic structure calculations
      is often cited as one of the principal applications of quantum computing. A great
      deal of theoretical algorithmic development has been performed in support of this
      goal. Most techniques require a scheme for mapping electronic states and
      operations to states of and operations upon qubits. The two most commonly used
      techniques for this are the Jordan-Wigner transformation and the Bravyi-Kitaev
      transformation. However, comparisons of these schemes have previously been
      limited to individual small molecules. In this paper, we discuss resource
      implications for the use of the Bravyi-Kitaev mapping scheme, specifically with
      regard to the number of quantum gates required for simulation. We consider both
      small systems, which may be simulatable on near-future quantum devices, and
      systems sufficiently large for classical simulation to be intractable. We use 86
      molecular systems to demonstrate that the use of the Bravyi-Kitaev transformation
      is typically at least approximately as efficient as the canonical Jordan-Wigner
      transformation and results in substantially reduced gate count estimates when
      performing limited circuit optimizations.

PMID- 30189145
TI  - Tailoring Site Specificity of Bioconjugation Using Step-Wise Atom-Transfer
      Radical Polymerization on Proteins.
AB  - Protein-polymer conjugates are powerful combinations of the biotic and abiotic
      worlds that impact many industries. Predicting the site and impact of polymer
      growth from the surface of proteins is only useful if we can use that information
      to choose which site to modify synthetically. We have explored the combination of
      a predictive algorithm with a unique stepwise atom-transfer radical
      polymerization (ATRP) to selectively move the predominant modification sites
      around a model enzyme. Lysozyme was modified with defined stoichiometric ratios
      of polymerization initiators and initiation inhibitors to selectively and
      strategically grow poly(carboxybetaine methacrylate) polymers from different
      protein sites. Electrospray ionization mass spectrometry was used to examine the
      uniformity of the lysozyme-initiator and lysozyme-inhibitor complexes prior to
      polymer growth. Bioactivity of the lysozyme-polymer conjugates was examined as a
      function of polymer location on the enzyme surface. Step-wise atom-transfer
      radical polymerization from proteins provides a versatile and modular approach
      that can be extended to the rational and selective design of other protein
      polymer conjugates.

PMID- 30189146
TI  - Assessing the Usefulness of Acute Physiological Responses Following Resistance
      Exercise: Sensitivity, Magnitude of Change and Time Course of Measures.
AB  - A variety of strategies exist to modulate acute physiological responses following
      resistance exercise aimed at enhancing recovery and/or adaptation processes. To
      assess the true impact of these strategies, it is important to know the ability
      of measures to detect meaningful change. We investigated the sensitivity of
      measures used to quantify acute physiological responses to resistance exercise
      and constructed a physiological profile to characterise the magnitude of change
      and time course of this response. Eight males, accustomed to regular resistance
      exercise, performed experimental sessions during a 'control week', void of an
      exercise stimulus. Participants repeated this sequence of experimental sessions
      the following week, termed the 'exercise week', except they performed a bout of
      lower-limb resistance exercise following baseline assessments. Assessments were
      conducted at baseline, 2, 6, 24, 48, 72 and 96 h post-intervention. Based on the
      signal-to-noise ratio, the most sensitive measures were maximal voluntary
      isometric contraction, 20m sprint, countermovement jump peak force, rate of force
      development (100-200ms), muscle soreness, daily analysis of life demands for
      athletes Part B, limb girth, matrix metalloproteinase-9, interleukin-6, creatine
      kinase and high sensitivity C-reactive protein with ratios of >1.5. There were
      clear changes in these measures following resistance exercise, determined via
      magnitude-based inferences. These findings highlight measures that can detect
      real changes in acute physiological responses following resistance exercise in
      trained individuals. Researchers investigating strategies to manipulate acute
      physiological responses for recovery and/or adaptation can use these measures, as
      well as recommended sampling points, to be confident that their interventions are
      making a worthwhile impact.

PMID- 30189147
TI  - Interleukin-15 as a myokine: mechanistic insight into its effect on skeletal
      muscle metabolism.
AB  - Interleukin-15 (IL-15) is a cytokine with important immunological functions. This
      cytokine is highly expressed in skeletal muscle and is believed to be a myokine.
      This hypothesis is supported by the rapid increase in circulating levels of IL-15
      in response to exercise. Treatment with high doses of IL-15 results in metabolic
      adaptations such as improved insulin sensitivity, whole-body fatty acid oxidation
      and protection from high-fat diet-induced obesity and insulin resistance. IL-15
      secreted by contracting muscle may therefore act as an endocrine factor to
      improve adiposity and energy metabolism in different tissues. Most of the time,
      studies used supraphysiological doses of IL-15 that do not represent circulating
      IL-15 in response to exercise. However, evidence shows that IL-15 levels are
      higher in muscle interstitium and IL-15 might improve muscle glucose homeostasis
      and oxidative metabolism in an autocrine/paracrine manner. Nevertheless, how IL
      15 signals in skeletal muscle to improve muscle energy metabolism is not
      completely understood, especially since the absence of the alpha subunit of the
      IL-15 receptor (IL-15Ralpha) results in a similar phenotype than
      overexpressing/oversecreting IL-15 in mice. In the present article, we review the
      literature to propose a model for the regulation of IL-15 by the secretable form
      of IL-15Ralpha to explain why some findings in the literature seem, at first
      glance, to be contradictory.

PMID- 30189148
TI  - Antibiotics: a risk factor for irritable bowel syndrome in a population-based
      cohort.
AB  - OBJECTIVES: Use of antibiotics affects the composition of the gut microbiome. The
      microbiome is thought to play a role in development of irritable bowel syndrome
      (IBS), but antibiotics as a possible risk factor for IBS has not been clarified.
      We aimed to explore if antibiotics is a risk factor for IBS by investigating use
      of antibiotics and development of IBS in a cohort from the Danish background
      population. MATERIALS AND METHODS: An internet-based web panel representative of
      the Danish background population was invited to participate in a survey regarding
      the epidemiology of IBS in 2010, 2011 and 2013. A questionnaire based on the Rome
      III criteria for IBS were answered at all three occasions. In 2013, a question
      regarding use of antibiotics in the past year was included. RESULTS: In 2013, use
      of antibiotics was reported by 22.4% (624/2781) of the population. A higher
      proportion of individuals with IBS reported use of antibiotics compared with
      asymptomatic controls [29.0% (155/534) vs. 17.9% (212/1,184), p < .01]. For
      asymptomatic respondents in 2010 and 2011 (n = 1004), the relative risk of IBS in
      2013 related with use of antibiotics was 1.9 [95% confidence interval (CI): 1.1
      3.1]. Adjusting for sex by logistic regression, development of IBS was predicted
      by use of antibiotics with an odds ratio of 1.8 (95% CI: 1.0-3.2). CONCLUSIONS:
      Antibiotics is a risk factor for IBS in asymptomatic individuals. Possible
      mechanisms should be investigated in future studies.

PMID- 30189149
TI  - Biological and Mechanical Evaluation of Novel Prototype Dental Composites.
AB  - The breakdown of the polymeric component of contemporary composite dental
      restorative materials compromises their longevity, while leachable compounds from
      these materials have cellular consequences. Thus, a new generation of composite
      materials needed to be designed to have a longer service life and ensure that any
      leachable compounds are not harmful to appropriate cell lines. To accomplish
      this, we have developed concurrent thiol-ene-based polymerization and allyl
      sulfide-based addition-fragmentation chain transfer chemistries to afford cross
      linked polymeric resins that demonstrate low shrinkage and low shrinkage stress.
      In the past, the filler used in dental composites mainly consisted of glass,
      which is biologically inert. In several of our prototype composites, we
      introduced fluorapatite (FA) crystals, which resemble enamel crystals and are
      bioactive. These novel prototype composites were benchmarked against similarly
      filled methacrylate-based bisphenol A diglycidyl ether dimethacrylate /
      triethylene glycol dimethacrylate (bisGMA/TEGDMA) composite for their
      cytotoxicity, mechanical properties, biofilm formation, and fluoride release. The
      leachables at pH 7 from all the composites were nontoxic to dental pulp stem
      cells. There was a trend toward an increase in total toughness of the glass-only
      filled prototype composites as compared with the similarly filled bisGMA/TEGDMA
      composite. Other mechanical properties of the glass-only-filled prototype
      composites were comparable to the similarly filled bisGMA/TEGDMA composite.
      Incorporation of the FA reduced the mechanical properties of the prototype and
      bisGMA/TEGDMA composite. Biofilm mass and colony-forming units per milliliter
      were reduced on the glass-only-filled prototype composites as compared with the
      glass-only-filled bisGMA/TEGDMA composite and were significantly reduced by the
      addition of FA to all composites. Fluoride release at pH 7 was greatest after 24
      h for the bisGMA/TEGDMA glass + FA composite as compared with the similarly
      filled prototypes, but overall the F- release was marginal and not at a
      concentration to affect bacterial metabolism.

PMID- 30189150
TI  - Ocular Manifestations of Human Immunodeficiency Virus Infection at a Tertiary
      Referral Center in Taiwan.
AB  - PURPOSE: To investigate the prevalence and characteristics of ocular
      manifestations of human immunodeficiency virus/acquired immunodeficiency syndrome
      (HIV/AIDS) in patients treated at a tertiary referral center in Taiwan during a
      time of highly active antiretroviral therapy (HAART) Materials and Methods: A
      retrospective cohort study in Taiwan was performed between January 2006 and July
      2016. Ocular examination and systemic information were recorded from the HIV
      infected patients. RESULTS: 1242 patients with HIV/AIDS were identified. Ninety
      patients had ophthalmic records, and HIV-related ocular manifestations were
      reported in 57 patients. The most prevalent ocular manifestations were
      cytomegalovirus (CMV) retinitis, ocular syphilis, and HIV microvasculopathy. Mean
      CD4 count was significantly lower in patients with HIV-related ocular
      manifestations compared to those without. CONCLUSION: We found that lower CD4
      count, especially <200 cells/MUL, was a significant factor for detecting HIV
      related ocular manifestations. Comprehensive ophthalmic screening in high-risk
      group is helpful for early diagnosis and prompt treatment of sight-threatening
      ocular complications.

PMID- 30189151
TI  - Immunopathological Features of Severe Chronic Atopic Keratoconjunctivitis and
      Effects of Topical Cyclosporine Treatment.
AB  - PURPOSE: To assess differential roles of inflammatory cells in pathophysiology of
      severe atopic keratoconjunctivitis (AKC) and evaluate immunomodulatory effects of
      topical cyclosporine A (CsA). METHODS: A total of 10 patients with severe,
      steroid-dependent/resistant chronic active AKC were treated using frequent
      topical CsA 0.05% as monotherapy for 2 months. Conjunctival biopsy specimens
      before and after treatment were examined using immunohistochemistry. A total of
      10 healthy age-matched adults served as the control group. RESULTS: Baseline AKC
      samples revealed greater cluster of differentiation 4 (CD4), interferon gamma
      (IFNgamma), human leukocyte antigen-D-related (HLA-DR) positive cell densities
      compared with healthy controls (P < 0.05), as well as interleukin (IL)-17 (P =
      0.08). Topical CsA treatment induced a significant reduction in CD4 and IL-17
      expressions (P < 0.05); post-treatment levels were same as normals (P > 0.05).
      Despite reduction after treatment (P = 0.06), HLA-DR expression remained higher
      than controls (P < 0.05). CONCLUSIONS: AKC-related conjunctival inflammation
      appears to be mediated by delayed hypersensitivity. In this short-term trial,
      frequent topical CsA improved conjunctival inflammation.

PMID- 30189152
TI  - The influence of preceding activity and muscle length on voluntary and
      electrically evoked contractions.
AB  - Muscle length and preceding activity independently influence rate of torque
      development (RTD) and electromechanical delay (EMD), however it is unclear
      whether these parameters interact to optimize RTD and EMD. The purpose of this
      study was to determine the influence of muscle length and preceding activity on
      RTD and EMD during voluntary and electrically stimulated (e-stim) contractions.
      Participants (n=17, males, 24 +/- 3yrs) performed isometric knee extensions on a
      HUMAC NORM dynamometer. Explosive maximal contractions were performed at 2 knee
      angles (35 degrees  and 100 degrees  referenced to a 0o straight leg) during an
      unloaded (UNL) contraction and preceding activations: 20, 40, 60, and 80% of
      maximum voluntary contraction (MVC) torque. Absolute and normalized voluntary RTD
      were slowed with preceding activities >=40% MVC for long muscle lengths and all
      preceding activities at short compared to UNL (p<0.001). Preceding activities of
      >=40% MVC for absolute and normalized e-stim RTD were slower than UNL (p<0.001)
      for both muscle lengths. Normalized RTD was faster at short muscle lengths than
      long (p<0.001) for e-stim (~50%) and voluntary (~32%) when UNL, however this
      effect was not present for absolute RTD. Muscle length did not affect EMD
      (p>0.05). At 80% MVC, EMD was shorter compared to UNL (~35%;p<0.001) for both
      muscle lengths during voluntary but not e-stim contractions. While RTD is limited
      by preceding activity at both muscle lengths, long muscle lengths require greater
      preceding activity to limit RTD than short muscle lengths which indicate long
      muscle lengths may offer a "protective effect" for RTD against preceding
      activity.

PMID- 30189153
TI  - Inflammatory bowel disease in patients over the age of 70 y. Does the disease
      duration influence its behavior?
AB  - INTRODUCTION: The fastest growing segment of our population is that of people
      above 70 years of age. Elderly patients with IBD exhibit several specific
      problems. Our objective was to evaluate the clinical course, the side effects of
      the treatments and the need for surgery of elderly patients, regardless of the
      age of onset. MATERIALS AND METHODS: This was a cross-sectional study wherein
      retrospective data were collected from multiple centers from seven hospitals
      within the Valencia metropolitan area. Data were collected on patients older than
      70 y with inflammatory bowel disease. RESULTS: We identified a total of 331
      patients older than 70 years of age (5.3% of patients monitored at our centers).
      The mean age at the time of the study was 77.34 y (+/-5.39). Mesalamine were the
      most frequently used medications. Corticosteroids were used in 66% of the
      patients. However, the use of corticosteroids and biologics was less probable in
      older patients (OR 0.96, p = .06). The longer the disease progressed, the more
      immunosuppressive medications were used (OR 1.3, p = .052). Neoplasms appeared in
      41 patients (13%). Of the 36 patients with tumors that appeared after the onset
      of the disease, 20 patients had not been treated with immunomodulators or
      biologics. CONCLUSIONS: Mesalamine was the most frequently used medication. There
      is no increased risk of tumors regarding the medications used. The use of
      immunosuppressive medications is more prevalent with longer disease progression
      times, although with a high rate of adverse events.

PMID- 30189154
TI  - Camellia oleifera seed extract attenuated abdominal and hepatic fat accumulation
      in rats fed a high-fat diet.
AB  - The objective of this study was to evaluate the effects of the hot-water extract
      of defatted Camellia oleifera seeds (CSE) on body and liver fat accumulation in
      rats. Forty rats were divided into five groups and each group was fed either an
      isocaloric control diet (C) or a high-fat liquid diet with 0% (H), 0.12% (H1),
      0.24% (H2), or 0.48% CSE (H3) for 8 weeks. Ingestion of the high-fat liquid diet
      increased abdominal and liver fat accumulation, although no difference was found
      in body weights compared to rats fed the control diet. We found that rats fed the
      H2 and H3 diets had lower plasma alanine aminotransferase activities than the H
      group in the 4th and 8th weeks. At the end of the study, the H2 and H3 groups
      also had lower epididymal and retroperitoneal fat masses, and all CSE groups had
      lower circulatory leptin levels than the H group. CSE consumption decreased
      hepatic fat accumulation in terms of liver triglycerides and a histopathology
      analysis, and ameliorated high-fat diet-induced elevation of hepatic tumor
      necrosis factor-alpha levels. We also found that CSE groups had lower
      malondialdehyde and hydroxyproline levels in the liver. Our results suggested
      that CSE may exert beneficial effects through decreasing body fat accumulation
      and hepatic steatosis and regulating adipokine levels in diet-induced non
      alcoholic fatty liver disease.

PMID- 30189155
TI  - American Association for Dental Research Policy Statement on Community Water
      Fluoridation.

PMID- 30189156
TI  - Is there sufficient evidence to explain the cause of sexually dimorphic behaviour
      in force steadiness?
AB  - Neuromuscular noise is a determining factor in the control of isometric force
      steadiness (FS), quantified as coefficient of variation (CV) of force around a
      preestablished target output. In this paper we examine sex-related differences of
      neural, muscular, and tendon influences on neuromuscular noise to understand FS
      in females and males. We use evidence from the literature to identify that CV of
      force is higher in females compared with males in the upper and lower body, with
      sex-related differences becoming less apparent with increasing age. Evaluation of
      sex-related physiology in tandem with results from FS studies indicate that
      differences in fibre type, contractile properties, and number of motor units
      (MUs) are unlikely contributors to differences in FS between females and males.
      MU type, behaviour of the population (inclusive of number of active MUs from the
      population), agonist-antagonist activity, maximal strength, and tendon mechanics
      are probable contributors to sexually dimorphic behaviour in FS. To clearly
      determine underlying causes of sex-related differences in FS, further study and
      reporting between females and males is required. Females and males are included
      in many studies; however, rich data on sexually dimorphic behaviour is lost when
      data are collapsed across sex or identified as nonsignificant without supporting
      values. This poses a challenge to identifying the underlying cause of females
      having higher CV of force than males. This review provides evidence of sexually
      dimorphic behaviour in FS and suggests that physiological differences between
      females and males effect neuromuscular noise, and in-turn contribute to sex
      related differences in FS.

PMID- 30189158
TI  - Cucumber mosaic virus Isolates from Greek Legumes are Associated with Satellite
      RNAs that are Necrogenic for Tomato.
AB  - Worldwide, Cucumber mosaic virus (CMV) is the causal agent of many economically
      important diseases. Based on immunological or molecular analysis, three distinct
      subgroups of CMV isolates can be identified (IA, IB, and II). In addition, some
      CMV isolates are associated with satellite RNAs (satRNAs), a type of noncoding
      transcript that may alter the symptoms of CMV infections. This study presents an
      analysis of CMV isolates occurring in legumes in Greece in respect to their
      genetic diversity, and the presence and diversity of their satRNA. Phylogenetic
      analysis of the CMV coat protein sequence of 18 legume and 5 tomato CMV isolates
      collected throughout Greece classified them within subgroups IA and IB, with a
      limited genetic diversity. The CMV satRNAs found in nine field legumes exhibiting
      mild symptoms and in one tomato with a necrotic syndrome contained a functional
      necrogenic motif; therefore, they were grouped within the necrogenic group of CMV
      satRNAs. The necrotic phenotype was expressed in all legume CMV isolates
      containing necrogenic satRNAs when mechanically inoculated onto tomato plants. To
      our knowledge, this is the first observation that legumes host necrogenic CMV
      satRNAs. The possible role of legumes in the epidemiology of CMV and necrogenic
      satRNA complex is discussed.

PMID- 30189157
TI  - Serum Amyloid A Contributes to Chronic Apical Periodontitis via TLR2 and TLR4.
AB  - In the current concept of bacterial infections, pathogen-associated molecular
      patterns (PAMPs) derived from pathogens and damage-associated molecular patterns
      (DAMPs) released from damaged/necrotic host cells are crucial factors in
      induction of innate immune responses. However, the implication of DAMPs in apical
      and marginal periodontitis is unknown. Serum amyloid A (SAA) is a DAMP that is
      involved in the development of various chronic inflammatory diseases, such as
      rheumatoid arthritis. In the present study, we tested whether SAA is involved in
      the pathogenesis of periapical lesions, using human periapical surgical specimens
      and mice deficient in SAA and Toll-like receptors (TLR). SAA1/2 was locally
      expressed in human periapical lesions at the mRNA and protein levels. The level
      of SAA protein appeared to be positively associated with the inflammatory status
      of the lesions. In the development of mouse periapical inflammation, SAA1.1/2.1
      was elevated locally and systemically in wild-type (WT) mice. Although SAA1.1/2.1
      double-knockout and SAA3 knockout mice had redundant attenuation of the extent of
      periapical lesions, these animals showed strikingly improved inflammatory cell
      infiltration versus WT. Recombinant human SAA1 (rhSAA1) directly induced
      chemotaxis of WT neutrophils in a dose-dependent manner in vitro. In addition,
      rhSAA1 stimulation significantly prolonged the survival of WT neutrophils as
      compared with nonstimulated neutrophils. Furthermore, rhSAA1 activated the NF
      kappaB pathway and subsequent IL-1alpha production in macrophages in a dose
      dependent manner. However, TLR2/TLR4 double deficiency substantially diminished
      these SAA-mediated proinflammatory responses. Taken together, the SAA-TLR axis
      plays an important role in the chronicity of periapical inflammation via
      induction of inflammatory cell infiltration and prolonged cell survival. The
      interactions of PAMPs and DAMPs require further investigation in dental/oral
      inflammation.

PMID- 30189159
TI  - Survey, Identification, and Characterization of Cylindrocarpon-Like Asexual
      Morphs in Spanish Forest Nurseries.
AB  - Cylindrocarpon-like asexual morphs infect herbaceous and woody plants, mainly in
      agricultural scenarios, but also in forestry systems. The aim of the present
      study was to characterize a collection of Cylindrocarpon-like isolates recovered
      from the roots of a broad range of forest hosts from nurseries showing decline by
      morphological and molecular studies. Between 2009 and 2012, 17 forest nurseries
      in Spain were surveyed and a total of 103 Cylindrocarpon-like isolates were
      obtained. Isolates were identified based on DNA sequences of the partial gene
      regions histone H3 (his3). For the new species, the internal transcribed spacer
      and intervening 5.8S nrRNA gene (ITS) region, beta-tubulin (tub2), and
      translation elongation factor 1-alpha (tef1) were also used to determine their
      phylogenetic position. Twelve species belonging to the genera Cylindrodendrum,
      Dactylonectria, and Ilyonectria were identified from damaged roots of 15
      different host genera. The species C. alicantinum, D. macrodidyma, D.
      novozelandica, D. pauciseptata, D. pinicola, D. torresensis, I. capensis, I.
      cyclaminicola, I. liriodendri, I. pseudodestructans, I. robusta, and I. rufa were
      identified. In addition, two Dactylonectria species (D. hispanica sp. nov. and D.
      valentina sp. nov.), one Ilyonectria species (I. ilicicola sp. nov.), and one
      Neonectria species (N. quercicola sp. nov.) are newly described. The present
      study demonstrates the prevalence of this fungal group associated with seedlings
      of diverse hosts showing decline symptoms in forest nurseries in Spain.

PMID- 30189160
TI  - How Will the General Data Protection Regulation Affect Healthcare?

PMID- 30189161
TI  - From the Editor's Desk - Quality in Surgery: From Quality of Care to Quality of
      Life.

PMID- 30189162
TI  - [The New Medical Licensing Examination in Portugal: The Questions Hold the
      Answers].

PMID- 30189163
TI  - ['Difficult Patients': A Perspective from the Tertiary Mental Health Services].

PMID- 30189164
TI  - The Costly War Against Cancer Treatment: The Example of Metastatic Renal Cell
      Carcinoma in Portugal.

PMID- 30189165
TI  - [Analysis of the Cochrane Review: Pregabalin for Pain in Fibromyalgia in Adults.
      Cochrane Database Syst Rev. 2016;9:CD011790 and 2016;4:CD009002].
AB  - Fibromyalgia can be clinically defined by widespread pain lasting for longer than
      3 months with tenderness on palpation in 11 or more of 18 specified tender
      points. Many people with fibromyalgia are significantly disabled, and experience
      moderate to severe pain for many years, for which conventional analgesics are
      usually not effective. For these patients treatment options generally include
      antidepressants like tricyclic agents, serotonin and noradrenaline reuptake
      inhibitors, or anticonvulsants like pregabalin or gabapentin. Pregabalin is a
      drug licensed for the treatment of fibromyalgia in the United States of America,
      with a mechanism of action similar to gabapentin. This mode of action confers
      antiepileptic, analgesic, and anxiolytic effects. This Cochrane systematic review
      included 8 randomized, placebo-controlled trials with low risk of bias, which
      studied the effect of a daily dose of pregabalin for the treatment of moderate to
      severe pain in adult patients suffering from fibromyalgia. Of the main results of
      this systematic review we highlight the major effect that a daily dose of 300 to
      600 mg of pregabalin had in the reduction of pain intensity over a follow-up
      period of 12 to 26 weeks, with tolerable adverse effects, for a minority of
      people with moderate to severe pain due to fibromyalgia. This paper aims to
      summarize and discuss the main results and conclusions of this systematic review,
      as well as its implications for the daily clinical practice.

PMID- 30189166
TI  - Translation and Validation of the Patient Activation Measure in Portuguese People
      with Type 2 Diabetes Mellitus.
AB  - INTRODUCTION: Management of diabetes mellitus is largely dependent on patients'
      active participation in care. The 'Patient Activation Measure 13' assesses
      patients' knowledge, skills, and confidence in self-care. We aimed to translate,
      culturally adapt, and validate the 'Patient Activation Measure 13' to Portuguese,
      in people with type 2 diabetes. MATERIAL AND METHODS: The translation and
      cultural adaptation occurred in six phases. A convenience sample of people with
      type 2 diabetes was recruited from the waiting rooms of a diabetes outpatient
      centre in Lisbon, between March and April 2014. The questionnaire was self
      administered; medical records were reviewed to obtain glycated haemoglobin
      levels. Main statistical analyses were based on the Rasch rating scale model.
      RESULTS: The response rate for the final questionnaire was 76%. Rasch analysis
      was conducted on 193 respondents. Respondents had a mean age of 67.1 (SD 10.1)
      years, 42.7% were women, and the mean patient activation measure score (0 - 100)
      in the sample was 58.5 (SD 10.1). The sample was low to moderate in terms of
      activation: 40.4% were low in activation (levels 1 and 2), 49.7% were in level 3,
      and 9.8% were in level 4, the highest level of activation. All items had good fit
      and the response categories functioned well. Item reliability was 0.97 and person
      reliability was between 0.77 (real) and 0.83 (model). DISCUSSION: The 'Patient
      Activation Measure 13' was translated and culturally adapted to European
      Portuguese and validated in people with diabetes, showing good psychometric
      properties. Future research should aim at evaluating test-retest reliability of
      the Portuguese 'Patient Activation Measure 13', and exploring its ability to
      measure changes in activation over time. CONCLUSION: The 'Patient Activation
      Measure 13' is now available in European Portuguese and has good psychometric
      properties.

PMID- 30189167
TI  - How is Bariatric Surgery Improving the Quality of Life of Obese Patients: A
      Portuguese Cross-Sectional Study.
AB  - INTRODUCTION: Obesity is often accompanied by psychological distress and both can
      reduce patients' quality of life. Bariatric surgery is proven to be a good method
      to reduce weight and to alleviate comorbidities, leading ultimately to an
      improvement in quality of life. MATERIAL AND METHODS: The authors studied 80
      patients enrolled in the Multidisciplinary Bariatric Unit of a central hospital
      in Porto, Portugal. Patients submitted to Roux-en-Y gastric bypass and sleeve
      procedures were compared. Laboratory parameters were collected from patients'
      files. Quality of life and psychological state - depression and anxiety, were
      evaluated using the Portuguese versions of the Medical Outcomes Study SF-36 and
      the hospital anxiety and depression scale, respectively, within one to two years
      of the surgery. RESULTS: A total of 51 patients were operated and completed a
      quality of life evaluation, while 21 patients were in a pre-operatory group
      (control). Patients subjected to bariatric surgery had higher scores of SF-36 and
      lower scores in both hospital anxiety and depression scale (anxiety and
      depression) subscales (p < 0.001); SF-36 presented a Pearson correlation
      coefficient of 0,475 (p = 0.004) with hemoglobin A1c. Sleeve had better results
      in the hospital anxiety and depression scale-depression subscale (p = 0.073).
      DISCUSSION: In this population, bariatric surgery led to better results,
      regarding both metabolic and psychological evaluations. No significant
      differences were found between gastric bypass and sleeve. However, further
      analyses must be performed. CONCLUSION: This study supports the theory that
      bariatric surgery contributes to the improvement of obese patients' quality of
      life and psychological state.

PMID- 30189168
TI  - [Does Aortic Valve Replacement Surgery Improve Patients' Quality of Life?]
AB  - INTRODUCTION: Aortic valve replacement surgery is done to increase patients' life
      expectancy and improve their health-related quality of life. Several published
      studies have found improvement in health-related quality of life after this
      procedure, but none have involved patients in Portugal. This study sought to
      evaluate patients' health-related quality of life after the implantation of
      aortic prostheses and compare these values with preoperative health-related
      quality of life and the general Portuguese population's health-related quality of
      life. MATERIAL AND METHODS: A retrospective study was done with elective patients
      who underwent implantation of an aortic prosthesis between August 2011 and April
      2016. Health-related quality of life was evaluated using the Short Form 36 Health
      Survey and Short Form 6 Health Survey questionnaires in the preoperative period
      and 3, 6 and 12 months post-surgery. Descriptive and inferential analyses were
      conducted to process the data and compare preoperative health-related quality of
      life with postoperative values and the Portuguese population's norms. RESULTS:
      The sample included 506 patients with an average age of 70.6 years. The majority
      are male (53.6%). The postoperative results show a statistically significant
      improvement compared to preoperative health-related quality of life in all eight
      dimensions of the Short Form 36 Health Survey. When contrasted with the general
      Portuguese population, patients' health-related quality of life is lower in the
      preoperative period, improving postoperatively and reaching higher than average
      health-related quality of life levels in some subgroups of patients and in
      various dimensions. An analysis of the Short Form 6 Health Survey results
      revealed that the patients undergoing this surgery have a higher level of
      preoperative problems compared with the general population, but these patients'
      values approach those of the general population by the end of one year post
      surgery. DISCUSSION: This is the first study in Portugal that compares health
      related quality of life using a validated scale, before and after the aortic
      prosthesis implantation surgery. The results demonstrate a significant
      improvement in all dimensions, which is not consistently observed in other
      published studies. CONCLUSION: The results confirm that the implantation of
      aortic prostheses improves patients' health-related quality of life, over time
      bringing it close to the general population's levels.

PMID- 30189169
TI  - Threats to Health and Well-Being Perceived by Older People in Poland and
      Portugal.
AB  - INTRODUCTION: According to the OECD, Portugal and Poland rank below average in
      several well-being measures such as income and wealth, and health status.
      Investigating how people perceive the threats to health in these two countries,
      is an important issue to address priority needs. To meet this need, the objective
      of this paper was to compare the perceptions of the threats to the health and
      well-being among the Polish and Portuguese older persons and explore differences
      between the countries in respect of patterns of self-rated health. MATERIAL AND
      METHODS: A Cross-sectional study with two convenience samples from primary health
      care services of Poland and Portugal was conducted; 480 adults aged 65 and over
      (247 Portuguese) were included. The EASYCare standard assessment of 2010 was
      applied under a joint project of both countries. The association between 'self
      rated unhealthy' and socio-demographic and threats to health variables was
      examined using logistic regression. RESULTS: In both countries about two thirds
      of the older persons self-rated their health as unhealthy. Having more than
      enough finances was associated with a significant lower odds of being unhealthy
      compared with those without enough finances at the end of the month (Portugal: OR
      = 0.25, 95% CI 0.10 to 0.63; Poland: OR = 0.33, 95% CI 0.12 to 0.88). Visual
      problems, bodily pain, memory loss, feeling bored or lonely and reporting
      shortness of breath during normal activities was consistently associated with
      fair or poor self-rated health. DISCUSSION: These findings provide important
      information regarding the health profile of older people which can help in the
      development of people-centred health systems where their lives and well-being can
      be improved. CONCLUSION: The unhealthy perception of older people was
      consistently associated with indicators of major health threats.

PMID- 30189170
TI  - [Gestational Diabetes Mellitus: Is There an Advantage in Using the Current
      Diagnostic Criteria?]
AB  - INTRODUCTION: There is no international consensus regarding gestational diabetes
      mellitus diagnostic criteria. In Portugal, the Carpenter and Coustan criteria
      were replaced by an adaptation of the International Association of Diabetes and
      Pregnancy Study Groups criteria. Our aim was to compare the incidence and
      outcomes of pregnancies complicated by gestational diabetes mellitus according to
      the current and previous criteria. MATERIAL AND METHODS: Retrospective analysis
      of 1218 singleton pregnancies complicated with gestational diabetes mellitus,
      with surveillance/delivery between 2008-2015. Two groups were considered:
      identification according to the Directorate-General of Health criteria -
      International Association of Diabetes and Pregnancy Study Groups (group 1);
      identification through Carpenter and Coustan criteria (group 2). A comparative
      analysis was performed. RESULTS: The incidence of gestational diabetes mellitus
      doubled (9.4% vs 4.6%), and the number of consultations/year increased (~3000 vs
      ~2000). In Group 1, in comparison with group 2, there was a lower risk of
      macrosomia in newborns [RR 0.44 (IC (95%):0.26 - 0.76)] and a higher risk of
      small for gestational age infants [RR 1.99 (IC (95%):1.19 - 3.31)]; a 6 - fold
      and 4 fold higher risk in neonatal hypoglycemia [RR 6.30 (IC (95%): 3.39 -
      11.71)] and hyperbilirubinemia [RR 3.89 (IC (95%): 2.25 - 6.72)] were also
      observed, respectively. There were no differences regarding other outcomes.
      DISCUSSION: Outcomes related to the decrease in macrosomia did now show any
      improvement, with even an increase in Small for Gestational Age and neonatal
      complications. Given the increased incidence of gestational diabetes mellitus,
      Directorate-General of Health - International Association of Diabetes and
      Pregnancy Study Groups criteria may be associated with greater healthcare-related
      costs due to more frequent consultations, with no apparent obstetrical/neonatal
      benefit. CONCLUSION: The Directorate-General of Health - International
      Association of Diabetes and Pregnancy Study Groups criteria were associated with
      a decrease in macrosomia, not accompanied by an improvement of
      obstetrical/perinatal outcomes. The benefit of using these criteria is open to
      debate.

PMID- 30189171
TI  - Quality Indicators in Ambulatory Surgery: A Literature Review Comparing
      Portuguese and International Systems.
AB  - INTRODUCTION: According to several studies conducted in North America and Europe,
      ambulatory surgery is a practice that has grown over the years, and both the
      number of more complex surgical procedures deemed suitable for ambulatory surgery
      and the number of patients with different co-morbidities which are now suitable
      for this type of procedure have been increasing. In order to respond to the
      increased number of day surgeries, as well as to avoid a potential proportional
      increase in perioperative morbidity, quality control systems must be adopted to
      enable continuous improvement and minimise predicted risks. The purpose of this
      study is to review global quality indicators used in ambulatory surgery and
      compare them with those used in Portugal. MATERIAL AND METHODS: The authors
      conducted a comprehensive search of medical databases, using MeSH words. Limits
      were applied to include only studies published after 1998 written in Portuguese,
      English and Spanish. Ambulatory surgery indicators for Portugal were also
      obtained. RESULTS: Twenty-one different quality indicators for ambulatory surgery
      were identified. The Portuguese Healthcare Regulation Authority has defined seven
      quality indicators for ambulatory surgery. DISCUSSION: The Portuguese quality
      indicators for ambulatory surgery are generally well adapted to current
      international practices. Nevertheless, after analysing the relevant international
      literature based on this study, it is important to consider two additional
      indicators for ambulatory surgery - same day surgery cancellations and patient
      satisfaction. CONCLUSION: On the literature review, same day surgery
      cancellations and patient satisfaction should be included in the National Health
      Assessment System created by the Portuguese Healthcare Regulation Authority.

PMID- 30189172
TI  - [Parona Space Abscess Derived from Dental Disease: Multidisciplinary Approach].
AB  - Parona Space infection is a rare forearm condition. We present a case of a 55
      year-old male with pain and loss of function in the distal forearm for one week,
      with no previous history of trauma. Additionally, he presented a history of
      odontogenic infection, synchronous with the onset of the symptoms in the forearm,
      with spontaneous resolution. The wrist ultrasound found an abscess in the Parona
      space that was surgically drained. The bacterial culture test was positive for
      Streptococcus constellatus. Oral evaluation revealed symptomatic exacerbation in
      the upper left second molar of chronic periodontitis. Oral septic foci were
      eliminated and the patient had full recovery. Dental history, the bacteria
      isolated and the absence of trauma confirm the dental origin of the abscess. As
      far as the authors are aware, this is the first published case of an odontogenic
      forearm abscess. This case highlights the importance of systematic elimination of
      oral septic foci in the population.

PMID- 30189173
TI  - [Subcutaneous Emphysema and Pneumomediastinum During a Tooth Extraction].
AB  - Subcutaneous emphysema is a possible but rare complication after dental
      procedures. The condition should be distinguished from other situations, such as
      hematoma, allergic reaction or angioedema, and infection. We describe the case of
      a 20-year-old puerperal woman, with multiple dental caries, who developed
      cervicofacial subcutaneous emphysema complicated by pneumomediastinum, following
      an incomplete extraction of the lower right second molar. This was diagnosed
      clinically and through imaging tests, and the situation resolved after hospital
      admission, with antibiotics and close monitoring. The case underlines the need to
      diagnose and treat this complication early, because of the risk of airway
      compromise, air embolism, infection, sepsis and death.

PMID- 30189174
TI  - Ulcerated Necrobiosis Lipoidica.

PMID- 30189175
TI  - [Letter to the Editor: The Concept of Dignity in Non-institutionalized Elderly
      People Cared for in Primary Health Care: A Preliminary Empirical Model].

PMID- 30189176
TI  - Letter to the Editor: More on Conflict of Interest Disclosure in a Top-Tier
      Portuguese Medical Journal.

PMID- 30189177
TI  - The European Medicines Agency and Family Doctors.

PMID- 30189178
TI  - [The New Medical Licensing Examination in Portugal: A Gigantic Millimeter Leap].

PMID- 30189179
TI  - [About 'The New Medical Licensing Examination in Portugal'].

PMID- 30189180
TI  - Emergency department models of care in Queensland: a multisite cross-sectional
      study.
AB  - Objective The acuity and number of presentations being made to emergency
      departments (EDs) is increasing. In an effort to safely and efficiently manage
      this increase and optimise patient outcomes, innovative models of care (MOC) have
      been implemented. What is not clear is how these MOC reflect the needs of
      patients or relate to each other or to ED performance. The aim of this study was
      to describe ED MOC in Queensland, Australia.Methods Situated within a larger
      mixed-methods study, the present study was a cross-sectional study. In early
      2015, leaders (medical directors and nurse managers) from public hospital EDs in
      Queensland were invited to complete a survey detailing ED activity, staffing
      profiles, treatment space, MOC and National Emergency Access Target (NEAT)
      performance. Routinely collected ED information system data was also used.Results
      Twenty of the 27 EDs invited participated in the study (response rate 74%). An
      extensive array of MOC were identified that were categorised into those that
      facilitate input, throughput and output from the ED. There was no consistent
      evidence as to the relative effectiveness of these MOC in achieving ED
      performance benchmarks, such as NEAT performance.Conclusion There is considerable
      variability in the MOC used throughout EDs in Queensland. A more complete
      analysis of the relative effectiveness of different MOC either in isolation or as
      part of a comprehensive approach would help inform more consistent MOC in
      Queensland EDs.What is known about the topic? MOC in any given ED are implemented
      in response to factors such as the geographical location of the hospital,
      hospital-specific characteristics and service profile, staffing profile and
      patient demographic profile. In the era of time-based targets, they may also
      serve to address a particular aspect of flow in the face of rising ED demand.
      Although many of the MOC attempt to deal with flow in a linear fashion, target
      specific phases of the ED journey or address particular patient cohorts, what is
      clear is that not all EDs are shaped and formed the same.What does this paper
      add? The study provides a comprehensive description of the varied models of care
      operating within Queensland public hospital EDs and how they relate to ED
      performance. A basic taxonomy of contemporary ED MOC is necessary to allow
      comparison between departments and inform decisions regarding safety, efficiency
      and cost-effectiveness.What are the implications to practitioners? A contemporary
      understanding of the presence and profile of ED MOC that currently exist within a
      network of hospitals and health services is important for managers, clinicians
      and patients to inform decision-making regarding the safety, clinical
      effectiveness and cost-effectiveness of these models. This understanding can also
      inform where and how further improvements in care delivery can progress.

PMID- 30189181
TI  - Operant over-responding is more sensitive than reversal learning for revealing
      behavioral changes after withdrawal from alcohol consumption.
AB  - In humans, prior alcohol use is linked with impulsivity and impaired decision
      making, but the nature of this relationship is unclear. In a previous study in
      rats, we found that prior alcohol access led to over-responding in go/no-go
      discrimination training, but had no effect on discrimination learning. It was
      unclear whether this over-responding effect would occur in a reversal learning
      task, or whether prior alcohol would impair reversal learning in our task. In the
      present experiments, we determined whether six weeks of chronic intermittent
      alcohol access would induce over-responding or impair reversal learning in our
      task. Our task allowed for multiple responses/trial with limited reinforcement,
      so over-responding could be assessed. In Exp. 1, we gave three days of
      discrimination training prior to access to 20% alcohol or water, then reversed
      task contingencies starting 4 days after the end of alcohol access. In Exp. 2, we
      gave either three or six days of discrimination training prior to the same
      alcohol access and reversal learning procedures to determine if the original
      training length would affect alcohol's behavioral effects. We found no reversal
      learning deficits in either experiment. Across both experiments, we found that
      the Alcohol group exhibited over-responding to the active lever, but this effect
      was smaller than in our previous discrimination experiments. Our data suggest
      that there are behavioral changes after voluntary alcohol access that can be
      missed by some discrimination/reversal learning assessments, and our over
      responding task can detect these transient changes. However, over-responding is
      more pronounced in discrimination than reversal learning.

PMID- 30189183
TI  - Outcome evaluations in group decision-making using authority rule: An
      electrophysiological study.
AB  - The present study aimed to investigate whether coincidence of opinion affects the
      evaluative processing of outcomes in group decision-making under authority rule.
      For this purpose, we examined the effects of the opinion coincidence on feedback
      related negativity (FRN), an event-related brain potential (ERP) reflecting the
      evaluative processing of outcomes. Six three-person groups performed a group
      decision-making task in which one member acting as a leader (leader blocks) made
      a group decision to choose one of two cards after he/she observed opinions of the
      other members acting as followers (follower blocks), and monetary gain or loss
      was contingent on the group decision. To examine the effect of the opinion
      coincidence, each trial of each individual was classified into one of three trial
      types: unanimous, majority, or minority trials. As a result, the amplitude of FRN
      was smaller for unanimous trials than for majority trials in the leader blocks.
      In addition, the amplitude of FRN was larger for majority trials compared to
      minority trials in the follower blocks. These results suggest that the
      coincidence of opinion in group decision-making affects the evaluative processing
      of outcomes, and this occurs even when roles and responsibilities over outcomes
      is explicitly clarified under the authority rule.

PMID- 30189182
TI  - Effects of diet on immune cells within the central nervous system.

PMID- 30189185
TI  - Editorial Comment.

PMID- 30189184
TI  - Role of hippocampal 5-HT1A receptors in the antidepressant-like phenotype of mice
      expressing RGS-insensitive Galphai2 protein.
AB  - A single base mutation in the Galphai2 protein (G184S) renders this Galpha
      subunit insensitive to the negative modulatory effects of Regulator of G-protein
      Signaling (RGS) proteins. Mice expressing this RGS insensitive (RGSi) variant of
      Galphai2 (RGSi Galphai2) display a spontaneous antidepressant-like phenotype that
      is reversible by treatment with the 5-HT1A receptor (5-HT1AR) antagonist
      WAY100635. Here we test the hypothesis that increased activity of 5-HT1ARs in the
      hippocampus of RGSi Galphai2 knock-in mice is responsible for the expression of
      the observed antidepressant-like behavior. We administered the 5-HT1AR antagonist
      WAY100635 or the agonist 8-OH-DPAT via bilateral intra-hippocampal infusion
      cannulae and evaluated antidepressant-like behavior using the tail suspension
      test (TST). WAY100635 reversed the antidepressant-like phenotype of the RGSi
      Galphai2 knock-in mice and 8-OH-DPAT produced an antidepressant-like response in
      wild type mice that was blocked by systemic WAY100635. Furthermore, intra
      hippocampal infusion of the RGS19/4 inhibitor CCG-203769 produced an
      antidepressant-like effect in female mice. Ex-vivo slice recording confirmed the
      5-HT1AR-mediated decrease in hippocampal CA1 pyramidal neuron excitability was
      enhanced in the RGSi Galphai2 knock-in mice. There was no change in hippocampal 5
      HT1AR expression as measured by ligand binding but there was a compensatory
      reduction in Galphai proteins. The findings demonstrate that RGS protein control
      of hippocampal 5-HT1AR signaling is necessary and sufficient to account for the
      antidepressant-like phenotype in the RGSi Galphai2 knock-in mice and that RGS
      proteins highly expressed in the hippocampus should be investigated as targets
      for novel antidepressant therapies.

PMID- 30189186
TI  - Which Patients with Negative Magnetic Resonance Imaging Can Safely Avoid Biopsy
      for Prostate Cancer?
AB  - PURPOSE: To determine if there is a sub-set of men who can avoid prostate biopsy
      (PBx), based on multi-parametric MRI (mpMRI) and clinical characteristics.
      MATERIALS AND METHODS: Of 1,149 consecutive men undergoing PBx (10/2011-03/2017),
      135 had a pre-biopsy negative mpMRI (Prostate Imaging-Reporting and Data System
      score<3). Detection rates of clinically-significant prostate cancer (CSPCa) were
      evaluated according to PSA density (PSAD) and prior biopsy history. CSPCa was
      defined as Grade Group >= 2. Multivariable logistic regression analysis was
      performed to identify predictors for non-CSPCa on biopsy. RESULTS: PCa and CSPCa
      detection rates were 38% and 18%, respectively. Men with biopsy-detected CSPCa
      had smaller prostates (p=0.004), higher PSAD (p=0.02) and no history of prior
      negative biopsy (p=0.01) compared to the non-CSPCa cohort. PSAD<0.15ng/mL/cc
      (p<0.001) and prior negative biopsy (p=0.005) were independent predictors of
      absence of CSPCa on biopsy. Negative predictive value of mpMRI for biopsy
      detection of CSPCa improved with decreasing PSAD, primarily in men with prior
      negative biopsy (p=0.001), but not for biopsy-naive men. Thirty-two percent of
      men had the combination of negative mpMRI, PSAD<0.15ng/mL/cc and negative prior
      biopsy; none had CSPCa on repeat biopsy. Incidence of biopsy-identified CSPCa in
      men with negative mpMRI only; men with negative mpMRI and PSAD<0.15ng/mL/cc; and
      men with negative mpMRI, PSAD <0.15ng/mL/cc and negative prior biopsy was 18%,
      10% and 0%, respectively. CONCLUSION: We propose a sub-set of men (with negative
      mpMRI, PSAD<0.15ng/mL/cc and prior negative biopsy) who may safely avoid re
      biopsy. Conversely, PBx should be considered in biopsy-naive men, regardless of
      negative mpMRI, particularly those with PSAD>0.15ng/mL/cc.

PMID- 30189187
TI  - Aberrant expression of vimentin predisposes oral premalignant lesion derived
      cells towards transformation.
AB  - OBJECTIVE: We have previously reported the aberrant expression of vimentin in
      human oral premalignant lesions and a 4-Nitroquinoline 1-oxide (4NQO) model of
      rat lingual carcinogenesis. Hence, we wanted to understand whether the expression
      of vimentin in early stage contributes to the process of transformation. STUDY
      DESIGN: Vimentin was stably expressed in oral premalignant lesion derived cells
      (vimentin negative) and various transformation related phenotypic assays were
      performed. Since vimentin alone failed to transform the cells, an additional
      carcinogenic stimulus benzo[a]pyrene (BP) was used. Concomitantly,
      immunohistochemistry (IHC) was performed on oral leukoplakia and tumor tissues
      for studying the expression of vimentin and E-cadherin. RESULTS: Exogenous
      expression of vimentin led to the appearance of EMT and stemness-related
      signatures. Further, upon BP treatment, vimentin expressing clones showed an
      increase in vitro and in vivo transformation efficiency. Importantly, high
      vimentin-low E-cadherin expression significantly correlated with the grade of
      dysplasia, as also with the lymph node metastasis in oral tumors. CONCLUSION: Our
      study suggests that the expression of vimentin in early stages may be beneficial,
      although not sufficient to achieve transformation. Further, high vimentin-low E
      cadherin expression, if validated in more number of early oral lesions, may prove
      useful in the identification of high risk human premalignant lesions.

PMID- 30189188
TI  - Haptoglobin phenotype is a critical factor in the use of fucosylated haptoglobin
      for pancreatic cancer diagnosis.
AB  - Fucosylation is one of the most important glycosylations involved in cancer and
      inflammation. Many studies have reported significant increases in serum
      fucosylated haptoglobin (Fuc-Hpt) in a variety of cancer patients. In this study,
      we measured Fuc-Hpt using a lectin-antibody enzyme-linked immunosorbent assay
      (ELISA) or a novel ELISA system that used a glycan antibody for Fuc-Hpt. Hpt is
      known to be divided into three phenotypes (Hpt1-1, Hpt2-1, and Hpt2-2), depending
      on its genetic background. Normal levels of serum Hpt are different in each Hpt
      phenotype and these phenotypes are associated with the incidence of several human
      diseases. Here, we investigated how Hpt phenotype affected measurements of Fuc
      Hpt, using two kinds of ELISA. Interestingly, we found that serum Fuc-Hpt levels
      were dramatically lower in the Hpt1-1 phenotype for both types of ELISA. For Hpt2
      1 and Hpt2-2, we observed significantly increased serum Fuc-Hpt levels in
      patients with pancreatic cancer. When cases of the Hpt1-1 phenotype were
      depleted, our receiver operating characteristic (ROC) curve analyses showed that
      the area under the curve (AUC) value for pancreatic cancer diagnosis increased in
      each ELISA. Taken together, our results indicate that Hpt phenotype is a critical
      for the clinical application of Fuc-Hpt as a cancer biomarker.

PMID- 30189189
TI  - Screening Heroin Smokers Attending Community Drug Services for COPD.
AB  - BACKGROUND: Heroin smoking is associated with deprivation, early onset severe
      emphysema, premature morbidity and mortality, and high use of health care, but
      individuals engage poorly with traditional health services. METHODS: In this
      cross-sectional study, we screened a population of heroin smokers, prescribed
      opiate substitution therapy by community drug services, for airway disease. We
      assessed drug exposure, respiratory symptoms, health status, and COPD prevalence.
      Subjects completed spirometry, completed Medical Research Council (MRC) Dyspnea
      Scale, COPD Assessment Tool (CAT) questionnaire, recorded drug exposure, and
      provided feedback. RESULTS: A total of 753 people (73% of those approached)
      completed screening, with 260 participants (35%) having COPD using FEV1/FVC < 0.7
      and 293 (39%) participants having COPD using the lower limit of normal. A further
      112 participants (15%) had asthma-COPD overlap (ACO) with features of COPD and
      asthma. Compared with those with normal spirometry, participants with COPD were
      more breathless (MRC score 3.1 vs 1.9; P < .001) and had worse health status (CAT
      score 22.9 vs 13.4; P < .001), respectively. Individuals with COPD had smoked
      cigarettes (P < .001), heroin (P < .001), and crack (P = .03) for longer and were
      more likely to still be smoking heroin (P < .01). Feedback was strongly positive,
      with 92% of respondents happy for other health-care appointments to be colocated
      with drug key worker appointments. CONCLUSIONS: Most heroin smokers had COPD or
      ACO, most commonly mild to moderate disease. In high-risk areas, screening this
      population provides an opportunity to reduce symptoms and risk. Anchoring
      respiratory health screening to drug center appointments delivers high completion
      and satisfaction and is an appropriate model for screening other hard-to-reach
      populations.

PMID- 30189190
TI  - Immune Checkpoint Immunotherapy for Non-Small Cell Lung Cancer: Benefits and
      Pulmonary Toxicities.
AB  - Immune checkpoint inhibitors (ICIs) are newer, immunotherapy-based drugs that
      have been shown to improve survival in advanced non-small cell lung cancer
      (NSCLC). Unlike traditional chemotherapeutic agents, ICIs work by boosting the
      body's natural tumor killing response. However, this unique mechanism of action
      has also led to the recognition of class-specific side effects. Labeled immune
      related adverse events, these toxicities can affect multiple organ systems
      including the lungs. Immune-mediated lung injury because of ICI use, termed
      checkpoint inhibitor pneumonitis (CIP), occurs in about 3% to 5% of patients
      receiving ICIs; however, the real-world incidence of this entity may be higher,
      especially now that ICIs are being used in nonclinical trial settings. In this
      review, we briefly introduce the biology of ICIs and the indications for ICI use
      in NSCLC and then discuss the epidemiology and clinical and radiologic
      manifestations of CIP. Next, we discuss management strategies for CIP, including
      the current consensus on management of steroid-refractory CIP. Given the nascent
      nature of this field, we highlight areas of uncertainty and emerging research
      questions in the burgeoning field of checkpoint inhibitor pulmonary toxicity.

PMID- 30189191
TI  - Identifying neuropeptide GPCRs in the mud crab, Scylla paramamosain, by
      combinatorial bioinformatics analysis.
AB  - Neuropeptides, ubiquitous signaling molecules, commonly achieve their signaling
      function via interaction with cell membrane-spanning G-protein coupled receptors
      (GPCRs). In recent years, in the midst of the rapid development of next
      generation sequencing technology, the amount of available information on encoded
      neuropeptides and their GPCRs sequences have increased dramatically. The
      repertoire of neuropeptides has been determined in many crustaceans, including
      the commercially important mud crab, Scylla paramamosain; however, determination
      of GPCRs is known to be more difficult and usually requires in vitro binding
      tests. In this study, we adopted a combinatorial bioinformatics analysis to
      identify S. paramamosain neuropeptide GPCRs. A total of 65 assembled GPCR
      sequences were collected from the transcriptome database. Subsequently these
      GPCRs were identified by comparison to known neuropeptide GPCRs based on the
      sequence-similarity-based clustering and phylogenetic analysis, which showed that
      many of them are closely related to insect GPCR families. Of these GPCRs, most of
      them were detected in various tissues of the mud crab and some of them showed
      differential expression by gender, suggesting they are involved in different
      physiological processes, such as sex differentiation. By employing ligand
      receptor binding tests, we demonstrated that the predicted crustacean
      cardioactive peptide (CCAP) receptor was activated by CCAP peptide in a dose
      dependent manner. This is the first CCAP receptor that has been functionally
      defined in crustaceans. In summary, the present study shortlists candidate
      neuropeptide GPCRs for ligand-receptor binding tests, and provides information
      for subsequent future research on the neuropeptide/GPCR signaling pathway in S.
      paramamosain.

PMID- 30189192
TI  - Changes in mRNA abundance of insulin-like growth factors in the brain and liver
      of a tropical damselfish, Chrysiptera cyanea, in relation to seasonal and food
      manipulated reproduction.
AB  - Food availability can become a factor driving the reproductive activity of
      tropical fish, particularly when primary production within their habitats
      fluctuates with tropical monsoons. The present study examined the involvement of
      insulin-like growth factors (IGF) in controlling the reproduction of the sapphire
      devil Chrysiptera cyanea, a reef-associated damselfish that is capable of
      manipulating its reproductive activity based on food availability. We cloned and
      characterized the cDNAs of igf1 and igf2 and determined their transcript levels
      in relation to seasonal and food-manipulated reproduction. The partial cDNAs of
      sapphire devil igf1 and igf2 had open reading frames (ORFs) composed of 600 bp
      (155 amino acid residue) and 636 bp (211 aa), respectively. Phylogenetic analyses
      revealed that IGF1 and IGF2 of the sapphire devil were clustered into those of
      teleosts. The gonadosomatic index increased from March to June. Vitellogenic
      oocytes and ovulatory follicles were observed in ovaries from May to June, which
      suggests that the spawning season lasts for at least 2 months. The hepatosomatic
      index, but not the condition factor, increased in March and June. The transcript
      levels of igf1 in the brain, but not in the liver, increased in April, June
      (vitellogenesis) and July (post vitellogenesis). Ovarian activity during the
      spawning season was maintained by high food supply (HH) for 30 days, although it
      was suppressed in the food-restriction treatment (LL) and restored in the re
      feeding treatment (LH). The transcript levels of igfs in the brain, but not in
      the liver, in LH were lower than those in HH and LL. Moreover, immersing fish in
      seawater containing estradiol-17beta suppressed transcript levels of igfs in the
      liver, but not in the brain. We conclude that reproductive activity during the
      spawning season is influenced by nutritive conditions and that crosstalk exists
      between the reproductive and growth network in the neural and peripheral tissues,
      thus controlling the reproductive activity of this species.

PMID- 30189194
TI  - Arterial-sided Oxygenator Clot and TCD Emboli in VA-ECMO.

PMID- 30189193
TI  - Minimally Invasive Approaches to Surgical Aortic Valve Replacement: A Meta
      Analysis.
AB  - BACKGROUND: Limited data exist studying the outcomes of the 2 minimally invasive
      aortic valve replacement (AVR) strategies-mini-sternotomy (AVR-st) and right
      anterior thoracotomy (AVR-th). We conducted an indirect meta-analysis to compare
      the outcomes of these minimally invasive approaches with each other and with
      conventional AVR (cAVR). METHODS: We Searched Medline, PubMed, Embase, and Web of
      Science in December 2017 for studies comparing AVR-st, AVR-th, and cAVR. Clinical
      outcomes were compared between cohorts with inverse weighted random effects
      modeling. Endpoints studied included hospital mortality, stroke, atrial
      fibrillation, cardiopulmonary bypass (CPB) time, and length of stay. RESULTS: A
      total of 19 studies (>10,000 pooled patients) met the inclusion criteria.
      Mortality (p = 0.06) and stroke (p = 0.15) were comparable between minimally
      invasive and conventional AVR. CPB times were longer with AVR-th versus cAVR
      (12.4 minutes [range, 5 to 19]; p < 0.01). In the AVR-th cohort, CPB duration was
      weakly inversely related to study size (p = 0.06). Atrial fibrillation was much
      less after AVR-th (odds ratio 0.47 [0.35 to 0.63]; p < 0.001). Hospital stay was
      significantly lower after minimally invasive surgery (0.8 [0.4 to 1.3] days; p <
      0.01). AVR-th patients were dismissed 2.1 (1.6 to 2.7) days earlier than cAVR
      patients. CONCLUSIONS: Minimally invasive approaches to AVR yield excellent
      outcomes in high-volume centers. They reduce hospital stay and incidence of
      postoperative atrial fibrillation, and therefore should be considered in patients
      undergoing AVR. The operative approach should be selected according to surgeon's
      technical expertise and what is best for specific patient profile, however.

PMID- 30189195
TI  - Maternal malnourishment induced upregulation of fetuin-B blunts nephrogenesis in
      the low birth weight neonate.
AB  - Maternal undernutrition during pregnancy (MUN) often leads to low birth weight
      (LBW) neonates that have a reduced total nephron endowment, leaving these
      neonates susceptible to kidney disease throughout their lives. For reasons
      unknown, these LBW neonates have impaired kidney development due to a severe
      reduction in renal SIX2+ stem cells during nephrogenesis. Using a mouse model of
      MUN, we investigated SIX2+ stem cell reduction in the LBW neonate. Significant
      upregulation of the protein fetuin-B (measured by PCR and immunoblotting) in the
      MUN mother's placenta, organs and circulation yielded a 3-fold increase of this
      protein in the embryonic kidney. Recombinant fetuin-B, administered to healthy
      pregnant mothers at the concentration equivalent to that in the MUN mother,
      crossed the placenta and reduced both SIX2+ stem cells by 50% and nephron
      formation by 66% in embryonic kidneys (measured by immunofluorescence and the
      physical dissector/fractionator stereological method). Administration of fetuin-B
      to kidney explants yielded similar reductions in renal SIX2+ stem cells and
      nephron formation. Fetuin-B treatment of isolated embryonic renal SIX2+ stem cell
      primary cultures 1) increased NF-kB activity and apoptosis, 2) reduced cell
      proliferation due to upregulated p21 nuclear activity and subsequent cell cycle
      arrest, and 3) enhanced generation of reactive oxygen species (measured by
      fluorescence microscopy). In conclusion, MUN increases fetuin-B in the developing
      embryonic kidney. The increase in fetuin-B blunts nephrogenesis by reducing SIX2+
      stem cells by promoting their apoptosis (via NF-kB upregulation), blunting their
      proliferative renewal (via p21 upregulation) and enhancing oxidative stress.

PMID- 30189196
TI  - Jasmonic acid-induced plant defenses delay caterpillar developmental resistance
      to a baculovirus: Slow-growth, high-mortality hypothesis in plant-insect-pathogen
      interactions.
AB  - Plants damaged by herbivore feeding can induce defensive responses that reduce
      herbivore growth. The slow-growth, high-mortality hypothesis postulates that
      these non-lethal plant defenses prolong the herbivore's period of susceptibility
      to natural enemies, such as predators and parasitoids. While many juvenile
      animals increase their disease resistance as they grow, direct tests of the slow
      growth, high-mortality hypothesis in the context of plant-herbivore-pathogen
      interactions are lacking. Caterpillars increase their resistance to lethal
      baculoviruses as they develop within and across instars, a phenomenon termed
      developmental resistance. Progression of developmental resistance can occur
      through age-related increases in systemic immune functioning and/or midgut-based
      resistance. Here, we examined the slow-growth, high-mortality hypothesis in the
      context of developmental resistance of caterpillars to baculoviruses. Intra
      stadial (within-instar) developmental resistance of the fall armyworm, Spodoptera
      frugiperda, to an oral inoculum of the baculovirus SfMNPV increased more rapidly
      with age when larvae were fed on non-induced foliage than foliage that was
      induced by jasmonic acid (a phytohormone that up-regulates plant anti-herbivore
      defenses). The degree of developmental resistance observed was attributable to
      larval weight at the time of virus inoculation. Thus, slower growth on induced
      plants prolonged the window of larval susceptibility to the baculovirus.
      Developmental resistance on induced and non-induced plants was absent when budded
      virus was injected intrahemocoelically bypassing the midgut, suggesting that
      developmental resistance was gut-based. Addition of fluorescent brightener, which
      weakens midgut-based resistance mechanisms to oral virus challenge, abolished
      developmental resistance. These results highlight the impact of plant defenses on
      herbivore growth rate and consequences for disease risk.

PMID- 30189197
TI  - Blue laser imaging-bright improves real-time detection rate of early gastric
      cancer: a randomized controlled study.
AB  - BACKGROUND AND AIMS: Blue laser imaging (BLI)-bright (BLI-bright) has shown
      promise as a more useful tool for detection of early gastric cancer (EGC) than
      white-light imaging (WLI). However, the diagnostic performance of BLI-bright in
      the detection of EGC has not been investigated. We aimed to compare real-time
      detection rates of WLI with that of BLI-bright for EGC. METHODS: This was a
      prospective, randomized, controlled study in 2 Japanese academic centers. We
      investigated 629 patients undergoing follow-up endoscopy for atrophic gastritis
      with intestinal metaplasia or surveillance after endoscopic resection of EGC.
      Patients were randomly assigned to receive primary WLI followed by BLI-bright or
      primary BLI-bright followed by WLI. The real-time detection rates of EGC were
      compared between primary WLI and primary BLI-bright. RESULTS: Of 298 patients in
      each group, the real-time detection rate of EGC with primary BLI-bright was
      significantly greater than that with primary WLI (93.1% vs 50.0%; p = 0.001).
      Primary BLI-bright had a significantly greater ability to detect EGCs in patients
      with a history of endoscopic resection for EGC, an HP-negative stomach after
      eradication therapy, lesions with an open-type atrophic border, lesions in the
      lower third of the stomach, depressed-type lesions, small lesions measuring <10
      mm and 10 to 20 mm in diameter, reddish lesions, well-differentiated
      adenocarcinomas, and lesions with a depth of invasion of T1a. CONCLUSIONS: BLI
      bright has a higher real-time EGC detection rate than WLI. BLI-bright should be
      performed during surveillance endoscopy in patients at high risk for EGC.

PMID- 30189198
TI  - Single-stage EUS-guided choledochoduodenostomy using a lumen-apposing metal stent
      for malignant distal biliary obstruction.
AB  - BACKGROUND AND AIMS: EUS-guided choledochoduodenostomy (EUS-CD) using a lumen
      apposing metal stent (LAMS) has recently been reported as an alternative
      treatment approach for patients with malignant obstructive jaundice and failed
      ERCP. We analyzed the safety and technical and clinical efficacy of EUS-CD using
      LAMSs in patients with malignant obstructive jaundice. METHODS: This was a
      retrospective study of consecutive patients with inoperable malignant distal bile
      duct obstruction who underwent EUS-CD using an electrocautery-enhanced (EC)-LAMS
      over a 3-year period (2015-2018). The main outcome measures were technical and
      clinical success (defined as a decline in serum bilirubin level by 50% at 2-week
      follow-up). Secondary outcomes were occurrence of adverse events, procedure time,
      and stent patency. RESULTS: Forty-six patients (47.8% women; median age, 73.1 +/-
      12.6 years) underwent direct EUS-CD using the biliary EC-LAMS. The procedure was
      technically successful in 43 patients (93.5%). The rate of clinical success was
      97.7%. Adverse events occurred in 5 (11.6%) patients and included the following:
      1 fatal bleeding 17 days after stent placement, 3 episodes of stent occlusion
      (food impaction), and 1 spontaneous migration (all 4 requiring reintervention).
      The mean follow-up was 114.37 days (95% confidence interval, 73.2-155.4).
      CONCLUSIONS: EUS-CD using the EC-LAMS is effective. The rate of adverse events
      including one fatal event is not negligible and should be carefully considered
      before using the stent in this clinical setting. Prospective studies are required
      to validate our preliminary findings to fully assess the long-term efficacy and
      safety of the stent.

PMID- 30189199
TI  - First detection of Anopheles stephensi Liston, 1901 (Diptera: culicidae) in
      Ethiopia using molecular and morphological approaches.
AB  - Malaria is a major public health concern in Ethiopia. With the increase in
      malaria cases in the Somali Region of Ethiopia, understanding the distribution
      and identifying the species of malaria vectors is vital to public health. Here we
      report the first detection of Anopheles stephensi in Ethiopia, a malaria vector
      typically found in the Middle East, the Indian subcontinent, and China, but
      recently found in Djibouti. An entomological investigation was conducted during
      November to December 2016 in Kebri Dehar town of the Ethiopian Somali Regional
      State as ancillary work for Anopheles spp. surveillance. Mosquito larvae were
      collected from water reservoirs. Larvae were reared in the laboratory to the
      adult stage and identified morphologically. PCR and sequencing of cytochrome
      oxidase 1 (COI) and internal transcribed spacer 2 (ITS2) loci were performed.
      Basic Local Alignment Search Tool (BLAST) was used to compare sample sequences to
      sequences in the NCBI nucleotide database for species identification. To further
      analyze the relationship between the specimen we collected in Kebri Dehar and
      other Anopheles samples available in Genbank, phylogenetic analysis was performed
      using a maximum likelihood approach. Molecular and morphological results confirm
      specimens were An. stephensi. The closest high scoring hit was for all specimens
      was for the An. stephensi sequence. Independent phylogenetic analyses of COI and
      ITS2 sequences revealed in both cases strong bootstrap (100) support for our
      sequence forming a clade with other An. stephensi sequences to the exclusion of
      any other species of Anopheles. In conclusion, Anopheles stephensi is present in
      Kebri Dehar town in Ethiopia. These findings highlight the need for additional
      research to examine the role of An. stephensi in malaria transmission in
      Ethiopia.

PMID- 30189201
TI  - Oligomerization and Auto-methylation of the Human Lysine Methyltransferase SETD6.
AB  - Signaling via lysine methylation by protein lysine methyltransferases (PKMTs),
      has been linked to diverse biological and disease processes. The mono
      methyltransferase SETD6 (SET-domain-containing protein 6) is a member of the PKMT
      family and was previously shown to regulate essential cellular processes such as
      the NF-kappaB, WNT and the oxidative stress pathways. However, on the biochemical
      level, little is known about the enzymatic mode of action of SETD6. Here we
      provide evidence that SETD6 forms high-molecular-weight structures. Specifically,
      we demonstrate that SETD6 monomeric, dimeric and trimeric forms are stabilized by
      the methyl donor, S-adenosyl-l-methionine. We then show that SETD6 has auto
      methylation activity at K39 and K179, which serves as the major auto-methylation
      sites with a moderate auto-methylation activity toward K372. A point mutation at
      K179 but not at K39 and K372, located at the SET domain of SETD6, impaired SETD6
      ability to form a trimer, strongly implying a link between the auto-methylation
      and the oligomerization state. Finally, by radioactive in vitro methylation
      experiments and biochemical kinetics analysis, we show that the auto-methylation
      at K39 and K179 increases the catalytic rate of SETD6. Collectively, our data
      support a model by which SETD6 auto-methylation and self-interaction positively
      regulate its enzymatic activity in vitro and may suggest that other PKMTs are
      regulated in the same manner.

PMID- 30189200
TI  - Molecular Basis of Class III Ligand Recognition by PDZ3 in Murine Protein
      Tyrosine Phosphatase PTPN13.
AB  - Protein tyrosine phosphatase PTPN13, also known as PTP-BL in mice, represents a
      large multi-domain non-transmembrane scaffolding protein that contains five
      consecutive PDZ domains. Here, we report the solution structures of the extended
      murine PTPN13 PDZ3 domain in its apo form and in complex with its physiological
      ligand, the carboxy-terminus of protein kinase C-related kinase-2 (PRK2),
      determined by multidimensional NMR spectroscopy. Both in its ligand-free state
      and when complexed to PRK2, PDZ3 of PTPN13 adopts the classical compact, globular
      D/E fold. PDZ3 of PTPN13 binds five carboxy-terminal amino acids of PRK2 via a
      groove located between the EB-strand and the DB-helix. The PRK2 peptide resides
      in the canonical PDZ3 binding cleft in an elongated manner and the amino acid
      side chains in position P0 and P-2, cysteine and aspartate, of the ligand face
      the groove between EB-strand and DB-helix, whereas the PRK2 side chains of
      tryptophan and alanine located in position P-1 and P-3 point away from the
      binding cleft. These structures are rare examples of selective class III ligand
      recognition by a PDZ domain and now provide a basis for the detailed structural
      investigation of the promiscuous interaction between the PDZ domains of PTPN13
      and their ligands. They will also lead to a better understanding of the proposed
      scaffolding function of these domains in multi-protein complexes assembled by
      PTPN13 and could ultimately contribute to low molecular weight antagonists that
      might even act on the PRK2 signaling pathway to modulate rearrangements of the
      actin cytoskeleton.

PMID- 30189204
TI  - Gyrification Needs Correct Sodium Flux!
AB  - Channelopathies are disorders that affect the function of ion channels, typically
      resulting in epilepsy. Smith et al. (2018) discover an unusual association
      between SCN3A, neuronal migration, and cortical folding, outlining sodium
      channels as important regulators of brain development.

PMID- 30189202
TI  - Prospection, Perseverance, and Insight in Sequential Behavior.
AB  - Real-world decisions have benefits occurring only later and dependent on
      additional decisions taken in the interim. We investigated this in a novel
      decision-making task in humans (n = 76) while measuring brain activity with fMRI
      (n = 24). Modeling revealed that participants computed the prospective value of
      decisions: they planned their future behavior taking into account how their
      decisions might affect which states they would encounter and how they themselves
      might respond in these states. They considered their own likely future behavioral
      biases (e.g., failure to adapt to changes in prospective value) and avoided
      situations in which they might be prone to such biases. Three neural networks in
      adjacent medial frontal regions were linked to distinct components of prospective
      decision making: activity in dorsal anterior cingulate cortex, area 8 m/9, and
      perigenual anterior cingulate cortex reflected prospective value, anticipated
      changes in prospective value, and the degree to which prospective value
      influenced decisions.

PMID- 30189205
TI  - The Tau of Nuclear-Cytoplasmic Transport.
AB  - Aggregation of microtubule-associated protein tau is the hallmark of tauopathies,
      including Alzheimer's disease. Eftekharzadeh et al. (2018) demonstrate that
      pathogenic tau alters nucleocytoplasmic transport by interacting with components
      of the nuclear pore complex, revealing a perturbation shared by multiple
      neurodegenerative diseases.

PMID- 30189206
TI  - Circuits for Raiders.
AB  - Heindorf et al. (2018) report that motor cortex plays a key role in behavioral
      tasks that rely on continuous sensory feedback. They propose a layer-based
      circuit that might be of particular importance when coping with unexpected
      perturbations in dynamic environments.

PMID- 30189207
TI  - Planning Your Way: How Humans Strategically Evaluate Prospective Decisions.
AB  - We are capable of planning ahead by incorporating dynamic factors influencing
      future choices. In this issue of Neuron, Kolling et al. (2018) present fMRI
      results of a novel task that demonstrates how humans evaluate alternative
      environments by prospectively incorporating their characteristics over time and
      account for their own decision tendencies.

PMID- 30189203
TI  - Common Variant Burden Contributes to the Familial Aggregation of Migraine in
      1,589 Families.

PMID- 30189208
TI  - Interplay between Oxytocin and Sensory Systems in the Orchestration of Socio
      Emotional Behaviors.
AB  - The neuropeptide oxytocin (OT) attracts the interest of neuroscientists,
      psychologists, and psychiatrists due to its capacity to modulate emotional and
      social behavior. Although much has been published on the effects of OT on brain
      regions and mechanisms at the core of these processes, its role in sensory
      processing, so important for detecting social context with sufficient accuracy
      and sensitivity, has been much less studied. In the present review, we summarize
      evidence for OT modulation of sensory processing and, conversely, effects of
      sensory input on endogenous OT signaling. We concentrate on mammals, aiming to
      provide a systematic analysis of the current knowledge on this reciprocal
      regulation and the role it may play in social and emotional behaviors.

PMID- 30189210
TI  - Chebulagic acid and Chebulinic acid inhibit TGF-beta1 induced fibrotic changes in
      the chorio-retinal endothelial cells by inhibiting ERK phosphorylation.
AB  - PURPOSE: Diabetic retinopathy (DR) is characterized by pro-inflammatory, pro
      angiogenic and pro-fibrotic environment during the various stages of the disease
      progression. Basement membrane changes in the retina and formation of
      fibrovascular membrane are characteristically seen in DR. In the present study
      the effect of Alcoholic (AlE) extracts of Triphala an ayurvedic herbal
      formulation and its chief compounds, Chebulagic (CA), Chebulinic (CI) and Gallic
      acid (GA) were evaluated for TGFbeta1-induced anti-fibrotic activity in choroid
      retinal endothelial cells (RF/6A). METHOD: RF/6A cells were treated with TGFbeta1
      alone or co-treated with AlE, CA, CI or GA. The mRNA and protein expression of
      fibrotic markers (alphaSMA, CTGF) were assessed by qPCR and western blot/ELISA.
      Functional changes were assessed using proliferation assay and migration assay.
      To deduce the mechanism of action, downstream signaling was assessed by western
      blot analysis along with in silico docking studies. RESULT: AlE (50 MUg/ml) CA
      and CI at 10 MUM reduced the expression of pro-fibrotic genes (alphaSMA and CTGF)
      induced by TGFbeta1, by inhibiting ERK phosphorylation. GA did not inhibit
      TGFbeta1 mediated changes in RF/6A cells. In silico experiments shows that CA and
      CI has favourable binding energy to bind with TGFbeta receptor and inhibit the
      downstream signaling, while GA did not. CONCLUSION: Hence this study identifies
      Triphala and its chief compounds CA and CI as potential adjuvants in the
      management of DR.

PMID- 30189211
TI  - Effects of experimental chronic traffic noise exposure on adult and nestling
      corticosterone levels, and nestling body condition in a free-living bird.
AB  - Transportation noise affects urbanized, rural, and otherwise unaltered habitats.
      Given expanding transportation networks, alterations in the acoustic landscapes
      experienced by animals are likely to be pervasive and persistent (i.e. chronic).
      It is important to understand if chronic noise exposure alters behavior and
      physiology in free-living animals, as it may result in long-lasting impacts, such
      as reduced reproductive success. Here, we experimentally tested the effects of
      chronic traffic noise on baseline and stress-induced corticosterone (the primary
      avian glucocorticoid), parental feeding behavior, and fitness proxies in breeding
      tree swallows (Tachycineta bicolor). Our results show that chronic traffic noise
      is related to altered corticosterone in both adult female and nestling tree
      swallows, suggesting that noise may be a stressor in both groups. In adult
      females, our results suggest that traffic noise is related to a limited ability
      to respond to subsequent acute stressors (i.e. reduced stress-induced
      corticosterone levels after handling). Further, our results show no evidence of
      habituation to noise during the breeding season, as the negative relationship
      between traffic noise and adult female stress-induced corticosterone became
      stronger over time. In nestlings, we found a positive relationship between
      traffic noise exposure and baseline corticosterone. Finally, we found a negative
      relationship between traffic noise and nestling body condition, despite no
      detectable effects of noise on nestling provisioning (e.g. parental feeding rate,
      or insect bolus size/composition). These results highlight the potential long
      term consequences of chronic noise exposure, as increased baseline corticosterone
      and reduced nestling body condition in noise-exposed areas may have negative,
      population-level consequences.

PMID- 30189212
TI  - Prokineticin-2 and ghrelin robustly influence the sexual and ingestive behaviors
      of female Syrian hamsters.
AB  - Prokineticins are involved in many physiological processes including circadian
      rhythms, neurogenesis, angiogenesis, and cancer. Recently, they have been found
      to play a role in regulating food intake. Historically, proteins that increase
      feeding behavior in mammals decrease reproductive behavior to prevent pregnancy
      and lactation when food is scarce. In the current study, prokineticin-2 (PK2) had
      pronounced effects on reproductive and ingestive behaviors when given to female
      Syrian hamsters. Administration of PK2 prevented ingestive behaviors induced by
      food restriction, such as the amount of time spent with food and eating. Hamsters
      given PK2 preferred to engage in reproductive behaviors, including spending time
      with a male and lordosis. Furthermore, analysis of blood plasma revealed that
      changes to behavior persisted despite similar levels of des-acyl ghrelin (DAG)
      and reduced glucose concentrations in the blood. Additionally, administering 10
      mg/kg of acyl ghrelin (AG) to a different cohort of animals significantly
      decreased the amount of time females spent with a potential mating partner,
      increased the amount of time females spent with food, decreased the duration of
      lordosis, and increased the duration of eating. Results from the current study
      support the need for further research investigating the reproductive and
      ingestive roles of PK2 and ghrelin.

PMID- 30189209
TI  - Tau Protein Disrupts Nucleocytoplasmic Transport in Alzheimer's Disease.
AB  - Tau is the major constituent of neurofibrillary tangles in Alzheimer's disease
      (AD), but the mechanism underlying tau-associated neural damage remains unclear.
      Here, we show that tau can directly interact with nucleoporins of the nuclear
      pore complex (NPC) and affect their structural and functional integrity.
      Pathological tau impairs nuclear import and export in tau-overexpressing
      transgenic mice and in human AD brain tissue. Furthermore, the nucleoporin Nup98
      accumulates in the cell bodies of some tangle-bearing neurons and can facilitate
      tau aggregation in vitro. These data support the hypothesis that tau can directly
      interact with NPC components, leading to their mislocalization and consequent
      disruption of NPC function. This raises the possibility that NPC dysfunction
      contributes to tau-induced neurotoxicity in AD and tauopathies.

PMID- 30189213
TI  - Multimodal stress detection: Testing for covariation in vocal, hormonal and
      physiological responses to Trier Social Stress Test.
AB  - Examining the effects of acute stress across multiple modalities (behavioral,
      physiological, and endocrinological) can increase our understanding of the
      interplay among stress systems, and may improve the efficacy of stress detection.
      A multimodal approach also allows for verification of the biological stress
      response, which can vary between individuals due to myriad internal and external
      factors, thus allowing for reliable interpretation of behavioral markers of
      stress. Here, controlling for variables known to affect the magnitude of the
      stress response, we utilized the Trier Social Stress Test (TSST) to elicit an
      acute stress response in 80 healthy adult men and women. The TSST involves an
      interview-style oral presentation and critical social evaluation, and is highly
      effective in inducing psychosocial stress. Participants completed the study in
      individual 2 h sessions, during which we collected voice, polygraph and salivary
      hormone measures in baseline, stress, and relaxation phases. Our results show
      sizeable systematic increases in voice pitch (mean, minimum and variation in
      fundamental frequency, F0), hormone levels (cortisol) and decreases in skin
      temperature and hand movement during psychosocial stress, with striking
      similarities between men and women. However, cortisol and skin temperature only
      weakly predicted changes in voice pitch during stress, in either women or men,
      respectively. Thus, while our results provide compelling evidence that
      psychosocial stress manifests itself behaviorally by increasing voice pitch and
      its variability alongside simultaneous activation of physiological and
      endocrinological stress systems, our results also highlight a relatively weak
      degree of intra-individual 'response coherence' across these stress systems, with
      dissociations among different stress measures related most strongly to sex.

PMID- 30189214
TI  - A severity index study of long-term prognosis in patients with chronic heart
      failure.
AB  - AIMS: The present study describes the derivation and validation of the Chronic
      Heart Failure Severity Index (CHFSI). MAIN METHODS: The CHFSI was derived using
      data obtained from a single-center prospective cohort study (2000-2014) that
      enrolled 756 patients. Logistic regression was used to identify independent
      predictors of mortality and quality of life over a 15-year follow-up period. KEY
      FINDINGS: The score was validated at the first 5-year (n = 644), second 5-year (n
      = 364), and third 5-year (n = 262). Independent predictors of mortality were
      older age (OR = 2.04, P < 0.001), etiology score (OR = 2.61, P < 0.001), faster
      heart rate (OR = 1.46, P = 0.027), higher systolic blood pressure (OR = 2.35, P <
      0.001), and left ventricular ejection fraction <=45% (OR = 1.97, P = 0.018). The
      derived CHFSI predicted the mortality, and the AUC for the logistic model was
      0.78 (95% confidence interval = 0.74-0.81, P < 0.001). Based on the logistic
      model, an integer scoring system was derived. Patients were classified into three
      groups: low risk (0-7 points), intermediate risk (8-11 points) and high risk
      (>=12 points) groups. The cumulative mortality for 15 years was 45.5% (125/275),
      84.0% (204/243), and 100% (99/99), respectively (P < 0.001). The 6-min walk test
      revealed a significant difference in quality of life among patients in the low,
      medium and high risk groups (all, P < 0.0001). SIGNIFICANCE: The CHFSI is a very
      useful clinical predictive tool that identifies patients at risk of future
      mortality and their quality of life across healthcare systems.

PMID- 30189215
TI  - Dietary macronutrient content affects inflammatory and fibrotic factors in normal
      and obstructed bladders.
AB  - AIMS: To investigate the effects of diets on factors and markers of inflammation
      and fibrosis in unobstructed and obstructed bladders of male Wistar rats.
      MATERIALS AND METHODS: Partial BOO was surgically induced in twelve-week old rats
      after feeding on different diets for eight (8) weeks. Feeding continued for 4
      weeks after surgery. Rats were divided into sham-operated and BOO groups as
      follow: control, high-carbohydrate (HCD), high-fat (HFD) and high-protein (HPD).
      After the feeding period, bladder weight, CRP, nerve growth factor (NGF), tissue
      growth factor-beta (TGF-beta), connective tissue growth factor (CTGF), hypoxia
      inducible factor-1alpha (HIF-1 alpha), platelet-derived growth factor-A (PDGF-A)
      and CXCL12 were all determined. KEY FINDINGS: In both unobstructed and obstructed
      bladders, CRP was increased in animals fed on the HFD (P < 0.05). NGF was
      increased in animals fed on HFD and HPD but decreased only in HCD-BOO. CXCL12 was
      increased in animals fed on HFD and HPD (P < 0.05) and decreased in HCD. The HCD
      BOO group exhibited a decrease in CXCL12, while CXCL12 increased in HFD-BOO. TGF
      beta was elevated in HFD and all the dietary-BOO groups, but animals with
      obstructed bladders fed on the HPD and HCD had significant reduction in TGF-beta
      expression. CTGF was increased in HFD- and HPD-fed animals. HIF-1alpha, PDGF-A
      and collagen were increased in both HFD dietary groups and HPD-BOO. SIGNIFICANCE:
      Feeding on a high fat diet results in increased activity of factors and mediators
      of inflammation and fibrosis in both unobstructed and obstructed rat bladders.
      This might increase predisposition to or further worsen symptoms in BOO.

PMID- 30189217
TI  - Peroxisome proliferator-activated receptor-gamma activation attenuates diabetic
      cardiomyopathy via regulation of the TGF-beta/ERK pathway and epithelial-to
      mesenchymal transition.
AB  - Diabetic cardiomyopathy (DCM) is a kind of disease caused by metabolic disorders
      and microangiopathy. The main pathophysiological changes of DCM include fibrosis,
      myocardial cell apoptosis and autonomic neuropathy. Therefore, treatment aimed at
      these processes may benefit patients with DCM. We designed an experiment with the
      peroxisome proliferator-activated receptor-gamma (PPARgamma) agonist GW 1929 to
      detect whether the activation of PPARgamma could alleviate the degree of DCM. To
      further detect the mechanism of PPARgamma in DCM, we used the PPARgamma
      antagonist GW 9662 and ERK antagonist PD 098059 both in vitro and in vivo and
      found that PPARgamma functioned by inhibiting ERK. We also performed Western
      blot, PCR, ELISA, immunohistochemistry, TUNEL assay, Sirius red staining and
      gelatin zymography to investigate inflammation, apoptosis, MMP activity and
      epithelial-to-mesenchymal transition (EMT). The results showed that the
      activation of PPARgamma inhibited these reactions and inhibiting ERK also
      simulated this phenomenon. In conclusion, these results demonstrated that
      PPARgamma activation in the diabetic myocardium of mice reduces myocardial
      fibrosis via regulation of the TGF-beta/ERK pathway and EMT.

PMID- 30189218
TI  - GAS5 promotes airway smooth muscle cell proliferation in asthma via controlling
      miR-10a/BDNF signaling pathway.
AB  - AIMS: To explore the role of long non-coding RNA (lncRNA) growth arrest-specific
      transcript 5 (GAS5) in the cell proliferation of airway smooth muscle cells
      (ASMCs) in asthma. MATERIALS AND METHODS: An asthma rat model was established by
      ovalbumin sensitization and challenge. The expression of GAS5, miR-10a and BDNF
      mRNA and protein was determined with qRT-PCR and western blot, separately. The
      targeting relationship between GAS5 and miR-10a was examined with RNA
      immunoprecipitation and RNA pull-down assay; the interaction between miR-10a and
      BDNF was evaluated by luciferase reporter assay. Cell Proliferation Assay (MTS)
      was used for ASMC proliferation detection. Knock-down of GAS5 was performed in
      asthmatic rats to determine the effects of GAS5 in vivo. KEY FINDINGS: Compared
      with control group, the inspiratory resistance and expiratory resistance were
      increased in asthma group; and the expression of GAS5, miR-10a and BDNF was
      higher, lower and higher, respectively. The expression of GAS5 and miR-10a was
      elevated and repressed, respectively, by platelet-derived growth factor-BB (PDGF
      BB). GAS5 functioned as a bait of miR-10a. GAS5 regulates BDNF expression through
      miR-10a. PDGF-BB promotes the cell proliferation of ASMCs through miR-10a/BDNF.
      Knock-down of GAS5 significantly decreased airway hyperresponsiveness in
      asthmatic rats. SIGNIFICANCE: The lncRNA GAS5/miR-10a/BDNF regulatory axis played
      an important role in promoting ASMCs proliferation, thus contributing to asthma.

PMID- 30189216
TI  - The reversal effect of physical exercise on aging-related increases in APPL2
      content in skeletal muscle.
AB  - AIMS: The aim of this study was to evaluate the effects of aging on intracellular
      adiponectin signaling and the possible therapeutic effect of physical exercise.
      MAIN METHODS: Fischer 344 rats were distributed in the following groups: Young (3
      months old); Sedentary Old (Old, 27 months old); and Old Exercised (Old-Exe, 27
      months old), which were subjected to a short-term exercise training protocol. KEY
      FINDINGS: The results showed that the old rats presented glucose intolerance
      without increased adiposity. However, short-term exercise training reversed this
      disorder, which was associated with a decrease in the pleckstrin homology domain,
      phosphotyrosine-binding domain, and leucine zipper motif (APPL) isoform 2 (APPL2)
      content. The APPL isoform 1 (APPL1) and TRB3 (Tribbles homolog 3) contents were
      not altered. Akt phosphorylation was only increased in the old exercised rats.
      There was a reduction in the content of adiponectin receptor 1 in the old rats.
      SIGNIFICANCE: The short-term exercise training protocol was able to decrease
      APPL2 content in the skeletal muscle, which was accompanied by an improvement in
      the glucose tolerance of the old Fischer 344 rats. These findings provide new
      evidence supporting the role of physical exercise as a non-pharmacological
      therapeutic intervention to attenuate age-related deficits.

PMID- 30189219
TI  - Toxicity of silver nanoparticles on different tissues of Balb/C mice.
AB  - AIM: The main purpose of the current study was to evaluate the toxicity of silver
      nanoparticles (Ag NPs) on adult Balb/C mice. MAIN METHODS: Twenty five Balb/C
      mice purchased and divided into four groups of five. Group one serves as control
      and injected by normal saline; group's two to four were injected by Ag NPs at
      0.25, 0.50 and 1 mg/kg, respectively. KEY FINDINGS: Overall, current results
      indicate that all concentration of Ag NPs have potential for induction of
      toxicity in different tissues. Ag NPs at concentration >0.25 mg/kg result in
      pathological changes in liver, spleen, brain, heart, lungs, kidneys, and
      testicles tissues; as well as it lead to significant change in sperm quality and
      quantity, and blood brain barrier (BBB) permeability. Ag NPs at the lowest
      concentration (0.25 mg/kg) significantly changed the oxidative stress levels in
      serum and liver tissue but did not change the level of liver enzymes and renal
      markers in serum. SIGNIFICANCE: The current research results support clearly the
      toxic effects of Ag NPs at very low concentration and suggest that further in
      vivo investigation are required to be able to confirm the safety of nanoparticle
      derived application to use in life.

PMID- 30189220
TI  - Glistening Formation and Light Scattering in Six Hydrophobic-Acrylic Intraocular
      Lenses.
AB  - PURPOSE: To study the glistening formation in various hydrophobic-acrylic
      intraocular lens (IOL) models, and to evaluate the effect of glistenings on light
      scattering in these IOLs. DESIGN: Laboratory investigation. METHODS: The
      susceptibility of the hydrophobic-acrylic material to develop glistenings was
      evaluated in 6 IOL models. Accelerated lens aging was induced by immersing the
      IOLs in a solution at 45 C for 24 hours and cooled to 37 C for 2.5 hours. Light
      microscopy and image acquisition were performed. Glistening statistics-that is,
      microvacuoles' (MV) number and size-were derived from image analysis. Light
      scattering was measured using a clinical device featuring an adaptation for in
      vitro IOL assessment. RESULTS: The number of glistenings differed among the
      studied IOLs and ranged from 0 to 3532 MV/mm2. In 1 model, glistenings were found
      only at the periphery, with diffuse light scattering observed centrally despite
      the absence of microvacuoles. The mean size of glistenings ranged from 5.2 to
      10.2 MUm. The mean straylight parameter of the IOLs increased from 0.6 to 5.0
      deg2/sr after accelerated aging. Straylight elevation demonstrated a proportional
      relationship with the glistening number. CONCLUSIONS: We showed that hydrophobic
      acrylic lenses differ in their resistance to glistenings, as one group proved to
      be glistening-free, but the other models revealed varying grades of glistenings.
      Moreover, we demonstrated that the presence of glistenings results in increased
      straylight, and that straylight proportionally depends on the glistenings number
      irrespective of the IOL model. However, more research is needed to confirm that
      the relationship we found holds for all hydrophobic-acrylic IOLs.

PMID- 30189221
TI  - Dose Effect and Stability of Postoperative Cyclodeviation After Adjustable Harada
      Ito Surgery.
AB  - PURPOSE: To report the dose-response relationship of adjustable Harada-Ito
      surgery, and postoperative stability of cyclodeviation. DESIGN: Retrospective
      cohort study. METHODS: Twenty patients underwent a unilateral adjustable Harada
      Ito advancement of the anterior fibers of the superior oblique tendon, with or
      without resection. The surgical dose was calculated as resection plus advancement
      plus adjustment. Cyclodeviation was measured using double Maddox rods at
      preoperative and postoperative time points. We assessed dose effect by
      calculating change in cyclodeviation from preoperatively to postadjustment and
      evaluated the dose-response relationship by Spearman rank methods. Postoperative
      stability of cyclodeviation was assessed by comparing postadjustment measurements
      with 1-day and 6-week measurements, and also 1- and 5-year measurements, when
      available. RESULTS: Change in cyclodeviation from preoperatively to
      postadjustment ranged from 7 to 20 degrees of incyclo effect. There was a dose
      effect of 1.3 degrees per mm (rs = 0.52, P = .019). Postoperative
      incyclodeviation unwound a mean of 3.6 degrees +/- 2.5 degrees between
      postadjustment and day 1. Overall change between postadjustment and the 6-week
      window was 6.5 +/- 2.9 degrees in an excyclo direction. Unwinding continued with
      a mean change of 0.2 +/- 2.6 degrees between the 6-week and 1-year windows, and
      of 0.4 +/- 2.1 degrees between 1-year and 5-years windows. CONCLUSIONS:
      Adjustable Harada-Ito advancement of the anterior fibers of the superior oblique
      tendon has a dose response of 1.3 degrees per millimeter, but its effect
      regresses over time. Based on our data, an immediate postoperative target
      incyclodeviation of 7 degrees is reasonable.

PMID- 30189222
TI  - Detection of carbapenem-resistant Enterobacteriaceae by chromogenic screening
      media.
AB  - Enterobacteriaceae are a part of the human intestinal flora easily spread by hand
      carriage, water and food. Treatment of infections due to Enterobacteriaceae is
      difficult mainly in countries with a low socioeconomic state. Carbapenems are
      considered as a last-resort antibiotic for the treatment of infections due to
      multidrug-resistant Enterobacteriaceae. Carbapenem-resistant Enterobacteriaceae
      (CRE) presents a major threat to public health and are rapidly disseminating
      globally. The most important resistance mechanism of Enterobacteriaceae to
      carbapenems is carbapenemase production. The treatment options for CRE are
      limited; attention is focused here on the rapid detection of CRE. Laboratory
      surveillance of cultures and screening of patients are essential and desirable in
      areas where these strains are endemic. Culture-based methods such as chromogenic
      media are used for the initial detection of these strains. These media offer a
      sensitive, convenient, and low-cost way of identifying CRE species. This article
      provides an overview of the current state of culture-based chromogenic screening
      media for the detection of CRE.

PMID- 30189223
TI  - Preparation, properties and challenges of the microneedles-based insulin delivery
      system.
AB  - Microneedle technology relates to pharmacy, polymer chemistry and micromachining.
      Microneedle can effectively deliver insulin into systemic circulation across the
      skin. This process does not affect the activity of insulin. Compared to
      subcutaneous injection, microneedles cause less pain for their special structure.
      This review thoroughly discusses the preparation technologies of the microneedles
      based insulin delivery system including solid, hollow, dissolving, phase
      transition, glucose-responsive microneedle patches. In the meantime, the
      properties, challenges and clinical/commercial status of the microneedles-based
      insulin delivery system are also discussed in this review.

PMID- 30189224
TI  - Pre-pregnancy obesity, gestational diabetes or gestational weight gain: Which is
      the strongest predictor of pregnancy outcomes?
AB  - AIMS: Both obesity and gestational diabetes (GDM) are risk factors for adverse
      pregnancy outcomes. The aim of our study is to ascertain the independent role of
      prepregnancy BMI (pp-BMI), gestational weight gain (GWG), and GDM on pregnancy
      outcomes. METHODS: We analyzed data of 1198 pregnant women, who underwent
      selective screening for GDM. Data on pregnancy outcomes was collected from
      hospital discharge records. RESULTS: Cesarean section (CS) was comparable in GDM
      and NGT women. Prevalence of fetal macrosomia was 5.9%, with no difference
      between GDM and normal glucose tolerance (NGT), neonatal hyperbilirubinemia were
      more frequent in newborns of GDM women (63.3% vs. 52.2%; p < 0.01). Offspring of
      women with excessive GWG weighed more than those of women with regular GWG (3405
      +/- 510 g vs. 3287 +/- 524 g; p < 0.01). On a logistic regression analysis, GWG
      was an independent risk factor for macrosomia (OR 1.08, 95% CI 1.02-1.13; p <
      0.01) and delivery at a gestational age <37 weeks (OR 0.29, 95% CI 0.16-0.53; p <
      0.0001). GDM and pp-BMI were not independent risk factors for adverse outcomes in
      this cohort. CONCLUSIONS: GWG rather than GDM is associated with adverse
      pregnancy outcomes. These findings call for an early education and implementation
      of a healthy lifestyle in women planning a pregnancy.

PMID- 30189225
TI  - Ribonucleic-acid-biomarker candidates for early-phase group detection of common
      cancers.
AB  - Cancer is considered as a challenging lethal agent around the world and its
      detection at early stages would help prevention of the high mortality. Among the
      widely used biomarkers in clinical diagnosis of cancer, extracellular non-coding
      RNAs as ribonucleic acid biomarkers serve as state-of-the-art candidates for
      molecular diagnosis. In that regard, microRNAs are of great priority mainly
      because of high variety and stability in body fluids. Accordingly, common miRNAs
      among most prevalent cancers could help us (pre)diagnose cancer with high
      accuracy in target samples. In this study, common lethal cancers to humans were
      investigated in case of miRNA profiles to determine the possible common
      correlation between miRNA up-regulation or down-regulation (as a ribonucleic acid
      biomarker) and developing the cancers. It was shown that among the investigated
      miRNAs, five typical extracellular miRNAs (miR-18a, miR-21, miR-155, miR-221, and
      miR-375) dysregulation are predominant in most cancer varieties comprising
      breast, colon, lung, prostate, pancreas, gastric, ovarian, esophagus and liver.
      This could serve as an appropriate target site for developing point-of-care
      approaches for cancer detection e.g. designing diagnostic biosensor-based
      microarrays or kits for both quantification and qualification of the biomarkers.
      Besides, the miRNA candidates could be efficiently applied to cancer therapeutic
      approaches.

PMID- 30189226
TI  - Cognitive-motor interference during gait in patients with Multiple Sclerosis: a
      mixed methods Systematic Review.
AB  - BACKGROUND: Cognitive-motor interference (CMI) has been proposed as a valid
      marker of daily life impairment in Multiple Sclerosis (MS). The heterogeneity and
      scarce number of studies regarding CMI in MS has hampered the synthesis of the
      existing evidence. The present systematic review employed a mixed methods
      approach with the aim of identifying and describing variables under which CMI is
      particularly useful to assess patients with MS. RESULTS: MS patients showed
      significant CMI. The motor variables that were most sensitive in detecting
      significant CMI were velocity (m/s), cadence (steps/min), and double support (%
      gait cycle), which was also specific for MS. Among the cognitive tasks, Alternate
      Alphabet and Serial Subtracting 7 s were sensitive, whereas Verbal Fluency were
      both sensitive and specific to CMI in MS. CONCLUSIONS: CMI should be assessed in
      MS with a standardised dual task such as the Verbal Fluency task while walking,
      with measurements of the double support time and the effect on the cognitive
      task. The clinical usefulness of CMI in the assessment of patients with MS is
      discussed.

PMID- 30189227
TI  - Variability in the Vestibulo-Ocular Reflex and Vestibular Perception.
AB  - The vestibular system enables humans to estimate self-motion, stabilize gaze and
      maintain posture, but these behaviors are impacted by neural noise at all levels
      of processing (e.g., sensory, central, motor). Despite its essential importance,
      the behavioral impact of noise in human vestibular pathways is not completely
      understood. Here, we characterize the vestibular imprecision that results from
      neural noise by measuring trial-to-trial vestibulo-ocular reflex (VOR)
      variability and perceptual just-noticeable differences (JNDs) in the same human
      subjects as a function of stimulus intensity. We used head-centered yaw rotations
      about an Earth-vertical axis over a broad range of motion velocities (0-65
      degrees /s for VOR variability and 3-90 degrees /s peak velocity for JNDs). We
      found that VOR variability increased from approximately 0.6 degrees /s at a chair
      velocity of 1 degrees /s to approximately 3 degrees /s at 65 degrees /s; it
      exhibited a stimulus-independent range below roughly 1 degrees /s. Perceptual
      imprecision ("sigma") increased from 0.76 degrees /s at 3 degrees /s to 4.7
      degrees /s at 90 degrees /s. Using stimuli that manipulated the relationship
      between velocity, displacement and acceleration, we found that velocity was the
      salient cue for VOR variability for our motion stimuli. VOR and perceptual
      imprecision both increased with stimulus intensity and were broadly similar over
      a range of stimulus velocities, consistent with a common noise source that
      affects motor and perceptual pathways. This contrasts with differing perceptual
      and motor stimulus-dependent imprecision in visual studies. Either stimulus
      dependent noise or non-linear signal processing could explain our results, but we
      argue that afferent non-linearities alone are unlikely to be the source of the
      observed behavioral stimulus-dependent imprecision.

PMID- 30189228
TI  - NGF and BDNF expression in mouse DRG after spared nerve injury.
AB  - Neuropathic pain is initiated by a primary lesion in the peripheral nervous
      system and spoils quality of life. Neurotrophins play important roles in the
      development and transmission of neuropathic pain. There are conflicting reports
      that the dorsal root ganglion (DRG) in an injured nerve contribute to neuropathic
      pain, whereas several studies have highlighted the important contribution of the
      DRG in a non-injured nerve. Clarifying the role of neurotrophins in neuropathic
      pain is problematic because we cannot distinguish injured and intact neurons in
      most peripheral nerve injury models. In the present study, to elicit neuropathic
      pain, we used the spared nerve injury (SNI) model, in which injured DRG neurons
      are distinguishable from intact ones, and mechanical allodynia develops in the
      intact sural nerve skin territory. We examined nerve growth factor (NGF) and
      brain-derived neurotrophic factor (BDNF) expression in the DRGs of SNI model
      mice. NGF and BDNF levels increased in the injured L3 DRG, while NGF decreased in
      the intact L5 DRG. These data offer a new point of view on the role of these
      neurotrophins in neuropathic pain induced by peripheral nerve injury.

PMID- 30189229
TI  - Alterations in mRNA expression of glutamate receptor subunits and excitatory
      amino acid transporters following pilocarpine-induced seizures in rats.
AB  - Temporal lobe epilepsy is the most prevalent form of complex partial seizure, and
      it is frequently triggered by an initial brain-damaging insult. The prevention of
      epileptogenesis after a primary event could be a key innovative approach to
      epilepsy treatment. Therefore, it is critical to understand the pathogenic
      mechanisms of this process in detail. Multiple mechanisms are involved in
      epileptogenesis, including alterations in the expression of synaptic receptors
      and transporters. The present study aimed to investigate the mRNA expression of
      excitatory amino acid transporters 1-3 (EAATs) and the subunits of the NMDA
      (GluN1, GluN2a, and GluN2b) and AMPA (GluA1 and GluA2) glutamate receptors
      following status epilepticus in a rat lithium-pilocarpine model. The analysis of
      the mRNA was performed via qRT-PCR one week after pilocarpine injections (the
      period of epileptogenesis) into the ventral and dorsal hippocampus and the
      entorhinal, temporal, and medial prefrontal cortexes - brain areas that are
      differentially involved in the pathogenesis of TLE. We found that increased EAAT2
      mRNA levels in the medial prefrontal cortex and dorsal hippocampus may represent
      compensatory neuroprotective changes. Alterations in the gene expression levels
      of AMPA receptor subunits were found in the ventral hippocampus and temporal
      cortex. The reduced expression of the GluN2a subunit was observed in the temporal
      and entorhinal cortical areas and the ventral hippocampus, which may result in
      the predominance of GluN2b-containing NMDA receptors in these areas. The
      receptors with this altered subunit composition may be involved in
      pathophysiological mechanisms related to epileptogenesis. These data provide a
      better understanding of the pathogenesis of epilepsy.

PMID- 30189230
TI  - Longevity of defective direct restorations treated by minimally invasive
      techniques or complete replacement in permanent teeth: A systematic review.
AB  - OBJECTIVES: This systematic review aimed to verify if there is difference in the
      longevity of minimally invasive techniques compared to the complete replacement
      for the treatment of defective direct restorations in permanent teeth. DATA: The
      data included randomized controlled clinical trials comparing the clinical
      performance of defective dental restorations treated by a complete replacement
      technique or minimally invasive techniques on permanent teeth. Evaluation of the
      risk of bias was performed using the Cochrane Collaboration common scheme for
      bias and the evidence was qualified using the GRADE tool. SOURCE: A comprehensive
      search was performed in the electronic databases: PubMed, Scopus, ISI Web of
      Science, The Cochrane Library, LILACS, BBO, SIGLE, followed by manual search in
      the reference lists of the included studies, without any restrictions. STUDY
      SELECTION: From 5554 retrieved studies, 10 met the eligibility criteria and were
      submitted to data extraction and quality assessment. The repair technique
      presented similar results to replacement and superior results when compared to
      sealing. In addition, refurbishment demonstrated to be a useful treatment for
      localized anatomical form defects. All the studies presented low risk of bias and
      high quality evidence for repair and refurbishment and moderate for the sealing
      technique. CONCLUSIONS: The direct restorations treated by the repair, seal and
      refurbishment techniques did not present a significant difference in clinical
      longevity in comparison to the replacement technique in permanent teeth with
      overall moderate quality of evidence. CLINICAL SIGNIFICANCE: The present findings
      demonstrated that the best treatment for defective restorations is conservative
      management. The evidence demonstrated here helps and encourages clinicians during
      the decision-making process. Moreover, it suggests not replacing imperfect
      restorations, but to managing them in a minimally invasive way, allowing the
      structure to be preserved.

PMID- 30189231
TI  - Voluntary exercise reverses immune aging induced by oxidative stress in aging
      mice.
AB  - Excessive oxidative stress leads to aging due to persistent damage to the cells,
      tissues, and the entire organism. Immunosenescence is also a devastating
      consequence of oxidative stress, but there is a lack of research on effective
      ways to overcome it. In this study, we used physiologic and immunological aging
      mouse models that had sustained oxidative stress to investigate whether voluntary
      exercise and/or antioxidant treatment could overcome oxidative damage as well as
      aging. We established an aging model induced by continuously administering d
      galactose (d-gal) to 6-week-old female C57BL/6J mice. We also assessed reversal
      of immunosenescence by providing free-wheel running and vitamin E (vit E)
      supplementation to this aging model. As an aging index, the level of advanced
      glycation end products (AGEs) in the blood was measured. Phenotypes of T cells in
      the thymus and spleen were examined as an index of immunosenescence.
      Intracellular reactive oxygen species (ROS) levels in the mouse spleen and levels
      of AGEs in the blood were significantly higher after 6 weeks of d-gal
      administration. In addition, immunosenescence was observed, in which the
      naive:effector cell ratio in the spleen decreased. After 4 weeks of free-wheel
      running and vit E administration, both intracellular ROS and serum AGE levels
      decreased. Above all, free-wheel running restored the naive:effector ratio of
      cytotoxic T lymphocytes reduced by d-gal administration. Taken together, these
      results suggest that voluntary exercise may be effective in restoring
      immunosenescence induced by oxidative stress.

PMID- 30189232
TI  - Experimentally unpacking cognitive behavioral therapy: The effects of completing
      a thought record on affect and neuroendocrine responses to stress.
AB  - Despite overall effectiveness of cognitive behavioral therapy (CBT), little is
      known about the effects of specific techniques used in CBT. Thought records are
      widely employed in CBT across disorders to target cognitions. The current study
      examined the effects of thought record completion on affective and physiological
      responses to a laboratory stressor. Participants underwent the Trier Social
      Stress Test (Kirschbaum & Hellhammer, 1993) and were randomized to a thought
      record condition (n = 50) or a control condition (n = 50). Affect and biological
      responses (i.e., cortisol, dehydroepiandrosterone, and alpha-amylase) were
      collected throughout the session. Participants in the thought record condition
      showed greater peak cortisol response following the stressor. No between group
      differences were found on other neuroendocrine or affect measures. Overall,
      results indicate completing a thought record impacts physiology (i.e., cortisol)
      and using experimental laboratory methods can provide additional information to
      inform our understanding of the components of CBT.

PMID- 30189233
TI  - New approach to differentiate primary from latent Toxoplasma gondii abortion
      through immunoglobulin and DNA interpretation.
AB  - BACKGROUND: Toxoplasma gondii is an acute or latent zoonotic abortifacient human
      protozoan. Women may be aborted due to recent or latent infection during
      pregnancy or order to flare up of the dormant bradyzoites to acute tachyzoites
      (latent opportunistic relapse). AIMS: 1) to validate the interpretation of IgM
      and IgG immunoglobulins seromonotoring with DNA comparative results in
      differentiating recent from latent T. gondii abortion. METHOD: Blood with the
      corresponding placental or uterine wash samples were collected from 73 aborted
      Egyptian women from Cairo and Giza labour wards. Patients aborted in any of the
      phases (Ph-1, Ph-2, Ph-3 and Ph-4 were corresponding to abortion at the 1st, 2nd
      and 3rd trimesters plus females who gave birth with congenital anomalies),
      respectively. All aborted patients were assayed serologically by Enzyme Linked
      Immunosorbent Assay (ELISA) for IgM and IgG titers and the compatible DNA from
      placenta and uterine wash tissues by conventional Polymerase Chain Reaction (PCR)
      specific for T. gondii. RESULTS: Sero-positive aborted women were 50.7% by ELISA
      versus 37% by PCR. Not all T. gondii sero-positive aborted women were having T.
      gondii DNA or harboring compatible placental T. gondii cysts. This denotes that
      immunoglobulins alone are insufficient criteria for confirming toxoplasma
      abortion. CONCLUSION: Immunoglobulins with DNA comparative results can possibly
      differentiate recent from latent T. gondii abortion at higher precision. We
      recommend the need for routine monitoring of T. gondii i.e. (pre-, during and
      post-delivery).

PMID- 30189234
TI  - Methods for the study of near, intermediate vision, and accommodation: an
      overview of subjective and objective approaches.
AB  - PURPOSE: To present an overview of contemporary methods and metrics used to
      measure near vision, intermediate vision, and accommodation. METHODS: A search in
      PubMed was performed with the following key phrases: near vision, intermediate
      vision, objective and subjective methods for the measurement of accommodation.
      For subjective methods, we included only those that are most widely used, had a
      scientific evidence of its outcomes, and have an easy availability at the
      doctor's office. For objective methods, we included those aberrometers or
      autorefractometers that have been proven to give good repeatability and
      reproducibility in the study of changes in optical power of the eye along the
      accommodative process. RESULTS: Near vision should be tested at 40 cm and
      intermediate vision at 63 or 80 cm. Accommodation should be measured with
      objective methods such as autorefractometers or aberrometers. CONCLUSIONS: The
      standardization for the measurement of near and intermediate vision, as well as
      the reading charts, will facilitate the comparison of visual outcomes between
      studies. Measurement of accommodation should be performed with objective methods
      as subjective methods tend to overestimate the accommodative power.

PMID- 30189236
TI  - ADC-histogram analysis in head and neck squamous cell carcinoma. Associations
      with different histopathological features including expression of EGFR, VEGF, HIF
      1alpha, Her 2 and p53. A preliminary study.
AB  - OBJECTIVE: Apparent diffusion coefficient (ADC) values derived from Diffusion
      weighted images are able to reflect tumor microstructure, such as cellularity,
      extracellular matrix or proliferation potential. This present study sought to
      correlate prognostic relevant histopathologic parameters with ADC values derived
      from a whole lesion measurement in head and neck squamous cell carcinoma (HNSCC).
      MATERIALS AND METHODS: Thirty-four patients with histological proven primary
      HNSCC were prospectively acquired. Histogram analysis was derived from ADC maps.
      In all cases, expression of Hif1-alpha, VEGF, EGFR, p53, p16, Her 2 were
      analyzed. RESULTS: In the overall patient sample, ADCmax correlated with p53
      expression (p = -0.446, p = 0.009) and ADCmode correlated with Her2-expression (p
      = -0.354, p = 0.047). In the p16 positive group there were several correlations.
      P25, P90 and entropy correlated with Hif1-alpha (p = -0.423, p = 0.05, p = 
      0.494, p = 0.019, p = 0.479, p = 0.024, respectively). Kurtosis correlated with
      P53 expression (p = -0.466, p = 0.029). For p16 negative carcinomas the following
      associations could be identified. Mode correlated with VEGF-expression (p = 
      0.657, p = 0.039). ADCmax, P75, P90, and Std correlated with p53-expression (p = 
      0.827, p = 0.002, p = -0.736, p = 0.01, p = -0.836, p = 0.001 and p = -0.70, p =
      0.016, respectively). There were no statistically significant differences of ADC
      histogram parameters between p16 positive and p16 negative carcinomas.
      CONCLUSION: ADC histogram values can reflect different histopathological features
      in HNSCC. Associations between ADC histogram analysis parameters and
      histopathology depend on p16 status.

PMID- 30189235
TI  - Inhibition of organic cation transporter (OCT) activities by carcinogenic
      heterocyclic aromatic amines.
AB  - Carcinogenic heterocyclic aromatic amines (HAAs) interact with some drug
      transporters, like the efflux pump BCRP and the organic anion transporters OAT1
      and OAT3. The present study was designed to determine whether they can also
      target activities of the organic cation transporters (OCTs), using mainly OCT1-,
      OCT2- and OCT3-overexpressing HEK293 cells. Fifteen HAAs were demonstrated to
      differently alter OCT activities; with a cut-off of at least 50% reduction of
      transporter activity by 100 MUM HAAs, 5/15 HAAs, including Trp-P-1 and Trp-P-2,
      inhibited activities of OCT1, OCT2 and OCT3, whereas 7/15 HAAs, including PhIP
      and MeIQx, blocked those of OCT2 and OCT3, 1/15 HAAs reduced those of OCT1 and
      OCT2 and 2/15 HAAs, including AalphaC, only that of OCT2. IC50 values of Trp-P-1
      and Trp-P-2 towards OCT activities were found to be in the 2-6 MUM range, likely
      not relevant for human exposure to HAAs through smoking or the diet. Trp-P-1 and
      Trp-P-2 additionally failed to trans-stimulate OCT1 and OCT2 activities and
      exhibited similar accumulation in OCT1/2-transduced HEK293 cells and control
      HEK293-MOCK cells. These data demonstrate that HAAs, notably Trp-P-1 and Trp-P-2,
      interact with OCT1/2, without however being transported, thus likely discarding a
      major role for OCT1/2 in HAA systemic toxicokinetics.

PMID- 30189237
TI  - Inhibition of chlorine-induced airway fibrosis by budesonide.
AB  - Chlorine is a chemical threat agent that can be harmful to humans. Acute
      inhalation of high levels of chlorine results in the death of airway epithelial
      cells and can lead to persistent adverse effects on respiratory health, including
      airway remodeling and hyperreactivity. We previously developed a mouse chlorine
      exposure model in which animals developed inflammation and fibrosis in large
      airways. In the present study, examination by laser capture microdissection of
      developing fibroproliferative lesions in FVB/NJ mice exposed to 240 ppm-h
      chlorine revealed upregulation of genes related to macrophage function. Treatment
      of chlorine-exposed mice with the corticosteroid drug budesonide daily for 7 days
      (30-90 MUg/mouse i.m.) starting 1 h after exposure prevented the influx of M2
      macrophages and the development of airway fibrosis and hyperreactivity. In
      chlorine-exposed, budesonide-treated mice 7 days after exposure, large airways
      lacking fibrosis contained extensive denuded areas indicative of a poorly
      repaired epithelium. Damaged or poorly repaired epithelium has been considered a
      trigger for fibrogenesis, but the results of this study suggest that inflammation
      is the ultimate driver of fibrosis in our model. Examination at later times
      following 7-day budesonide treatment showed continued absence of fibrosis after
      cessation of treatment and regrowth of a poorly differentiated airway epithelium
      by 14 days after exposure. Delay in the start of budesonide treatment for up to 2
      days still resulted in inhibition of airway fibrosis. Our results show the
      therapeutic potential of budesonide as a countermeasure for inhibiting persistent
      effects of chlorine inhalation and shed light on mechanisms underlying the
      initial development of fibrosis following airway injury.

PMID- 30189238
TI  - GSK-3 inhibition through GLP-1R allosteric activation mediates the neurogenesis
      promoting effect of P7C3 after cerebral ischemic/reperfusional injury in mice.
AB  - An aminopropyl carbazole compound, P7C3, has been shown to be a potent
      neurogenesis promoting agent; however, its fundamental signaling action has yet
      to be elucidated. A cerebral ischemic/reperfusional (CI/R) injury model in mice
      was implemented to elucidate the neuronal protective mechanism(s) of P7C3.
      Treating CI/R mice using P7C3 (50-100 MUg/kg, i.v.) significantly improved
      tracking distance and walking behavior, and reduced brain damage. Specifically,
      P7C3 promoted the expression of neurogenesis-associated proteins, including
      doublecortin, beta tubulin III (beta-tub3), adam11 and adamts20, near the peri
      infarct cortex, accompanied by glycogen synthase kinase 3 (GSK-3) inhibition and
      beta-catenin upregulation. The application of a specific inhibitor against
      glucagon-like peptide 1 receptor (GLP-1R), exendin(9-39), revealed that the
      beneficial effects of P7C3 involved triggering the activation of GLP-1R
      associated PKA/Akt signaling. P7C3 elicited the GLP-1R-dependent intracellular
      cAMP increment and the insulin secretion in cellular models. Surface plasmon
      resonance assay of P7C3 showed a Kd value of 0.53 MUM for GLP-1R binding, and the
      docking of P7C3 to the putative active site on GLP-1R was successfully predicted
      by molecular modeling. Our findings indicate that P7C3 promotes the expression of
      neurogenesis proteins by activation of the cAMP/PKA-dependent and Akt/GSK3
      associated beta-catenin through positive allosteric stimulation of GLP-1R. Within
      the P7C3 class of neuroprotective molecules, this mechanism appears to be unique
      to the prototypical P7C3 molecule, as other active derivatives such as P7C2-A20
      and P7C3-S243 they do not engage this same pathway and have been shown to work by
      nicotinamide phosphoribosyltransferase (NAMPT) stimulation.

PMID- 30189239
TI  - The effects of a continuous 1-h a day 900-MHz electromagnetic field applied
      throughout early and mid-adolescence on hippocampus morphology and learning
      behavior in late adolescent male rats.
AB  - The purpose of this study was to investigate hippocampus morphology and changes
      in learning behavior in male rats in late adolescence exposed to the effect of a
      continuous 1-h a day 900-megahertz (MHz) electromagnetic field (EMF). Twenty-four
      male Sprague Dawley rats aged 3-weeks were divided equally into control, sham and
      EMF groups. EMF group rats were exposed to a 900-MHz EMF inside an EMF cage,
      while the sham group rats were placed in the same cage but were not exposed to
      such an effect. No procedure was performed on the control group. Following 25-day
      application of EMF, passive avoidance, 8-arm radial maze and Y-maze tests were
      applied to determine rats' learning and memory performances. Open field and
      rotarod tests were applied to assess locomotor activity. At the end of the tests,
      the animals' brains were removed. Sections were taken and stained with toluidine
      blue. The regions of the hippocampus were subjected to histopathological
      evaluation. At histopathological examination, impairments of pyramidal and
      granular cell structures were observed in the EMF group hippocampus. No
      significant change was observed in learning, memory or locomotor behavior in any
      group. In conclusion, 900-MHz EMF applied in early and mid-adolescence causes no
      changes in learning, memory or locomotor behavior.

PMID- 30189240
TI  - Acridone alkaloids from the stem bark of Citrus aurantium display selective
      cytotoxicity against breast, liver, lung and prostate human carcinoma cells.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Citrus aurantium L. (Rutaceae) is used, either
      singly or as a part of a polyherbal preparation, in Nigerian traditional medicine
      for the management of cancer and inflammatory diseases. Currently, there is a
      dearth of knowledge demonstrating its anticancer potential. AIM OF THE STUDY:
      This study was carried out to determine the in vitro cytotoxicity of the crude
      extract of the stem bark of C. aurantium, identify and isolate the bioactive
      constituents and to establish the cytotoxicity of such constituents. MATERIALS
      AND METHODS: The powdered bark of C. aurantium was extracted by MeOH at room
      temperature (25-34  degrees C) and the crude extract was partitioned
      successively, with n-hexane, dichloromethane and methanol. Amongst the fractions,
      the DCM fraction was the most active and compounds were isolated from this
      fraction using a combination of chromatographic techniques. The structures of the
      isolated compounds were elucidated by spectroscopic means (MS, 1D and 2D NMR).
      The cytotoxicity of the extract, and the isolated compounds were evaluated by the
      MTT assay against four human cancer cell lines: A549 (lung), HepG2 (liver), MCF7
      (breast) and PC3 (prostate). The selectivity of the isolated compounds was
      assessed using the normal human prostate epithelium cells (PNT2). RESULTS AND
      DISCUSSION: Of the three plant fractions, the DCM fraction showed significant
      cytotoxicity, with its highest activity against A549 cells (IC50 = 3.88 ug/mL)
      and the least activity on HepG2 cells (IC50 = 5.73 ug/mL). Six acridone
      alkaloids, citrusinine-I (1), citracridone-I (2), 5-hydroxynoracronycine (3),
      natsucitrine-I (4), glycofolinine (5) and citracridone-III (6), were isolated
      from the DCM fraction of C. aurantium. The isolated compounds demonstrated potent
      to moderate cytotoxicity (IC50 = 12.65-50.74 uM) against the cancer cells under
      investigation. It is noteworthy that the compounds exerted cytotoxicity at least
      four times more selective towards the carcinoma cells than the PNT2 cells.
      CONCLUSION: The results obtained from this study have provided some evidence for
      the ethnomedicinal use of C. aurantium against cancer and the acridone alkaloids
      present in its stem bark, have appeared to be responsible for the anticancer
      effects.

PMID- 30189241
TI  - Transcriptome analysis reveals novel genes and immune networks dysregulated in
      veterans with PTSD.
AB  - BACKGROUND: Posttraumatic stress disorder (PTSD) is a serious condition that
      emerges following trauma exposure and involves long-lasting psychological
      suffering and health-issues. Uncovering critical genes and molecular networks is
      essential to understanding the biology of the disorder. We performed a genome
      wide scan to identify transcriptome signatures of PTSD. METHODS: Genome-wide
      peripheral blood transcriptomic data from 380 service personnel were
      investigated. This included a discovery sample of 96 Australian Vietnam War
      veterans and two independent pre and post-deployment replication samples of U.S.
      Marines (N = 188 and N = 96). RESULTS: A total of 60 transcripts were
      differentially expressed between veterans with and without PTSD, surviving
      Bonferroni multiple testing correction. Genes within the cytokine-cytokine
      receptor interaction, Jak-STAT signaling and Toll-like receptor signaling
      pathways were enriched. For 49% of the genes, gene expression changes were also
      accompanied by DNA methylation changes. Using replication data from two U.S.
      Marine cohorts, we observed that of the differentially expressed genes, 71% genes
      also showed significant gene expression changes between pre and post-deployment.
      Weighted gene co-expression networks revealed two modules of genes associated
      with PTSD. The first module (67 genes, p-value = 6e-4) was enriched for genes
      within the 11p13 locus including BDNF. The second module (266 genes, p-value =
      0.01) was enriched for genes in 17q11 including SLC6A4, STAT5A and STAT5B.
      CONCLUSIONS: We identified novel transcriptomic loci and biological pathways for
      PTSD in service personnel. Network analysis revealed enrichment of loci harboring
      key candidate genes in PTSD. These findings highlight the role of transcriptional
      biomarkers in the molecular etiology of PTSD.

PMID- 30189242
TI  - Venom gland transcriptomics and microRNA profiling of juvenile and adult yellow
      bellied sea snake, Hydrophis platurus, from Playa del Coco (Guanacaste, Costa
      Rica).
AB  - With an extensive range in tropical and subtropical waters of Indo-Australian
      region and the Pacific coast of the American continent, the yellow-bellied sea
      snake, Hydrophis platurus, is the most broadly distributed snake species on our
      planet. We report a comparative analysis of the mRNA and microRNA transcriptional
      profiles of the venom glands of Costa Rican juvenile and adult yellow-bellied sea
      snakes, and correlate these datasets with the previously reported venom proteome
      gathered from an adult specimen of the same population of Playa del Coco. The
      transcriptomic profiles are qualitatively and quantitatively remarkably similar
      across both age classes, being overwhelmingly (>99%) dominated by only three
      toxin classes, three-finger toxins (3FTx, 88%), phospholipases A2 (PLA2, 10-11%),
      and cysteine-rich secretory proteins (CRISP, 1%). The only appreciable difference
      between the transcriptomes of juvenile and adult Costa Rican yellow-bellied sea
      snake lies in the relative abundance of short and long neurotoxic 3FTxs.
      Comparison of venom gland transcriptome and venom proteome datasets suggest that
      the venom arsenal of adult H. platurus from Playa del Coco (CR) is subjected to
      post-transcriptional modulation, involving repression of the translation of
      pelamitoxin a-encoding mRNAs and enhancement of the translational activity of
      PLA2 and CRISP mRNAs.

PMID- 30189243
TI  - Assessment of quality, safety, and pre-clinical toxicity of an equine polyvalent
      anti-snake venom (Pan Africa): Determination of immunological cross-reactivity of
      antivenom against venom samples of Elapidae and Viperidae snakes of Africa.
AB  - Snakebite causes a large amount of morbidities and mortalities in Africa. The
      safety, efficacy, and homogeneity of anti-snake venoms are crucial for snakebite
      treatments to be effective with minimal adverse effects. We assessed the
      homogeneity of preparations of three different batches of Combipack snake venom
      antiserums (Pan Africa) [CSVAPA] by quantitatively analysing F(ab')2, IgG, and
      other contaminating proteins of plasma. LC-MS/MS analysis showed that
      approximately 92.4% of the proteins from the CSVAPA samples was IgG/F(ab')2 and
      the percent composition of contaminating proteins in CSVAPA varied from 0.07 to
      4.6%. Batch 1 of the CSVAPA also contained a minor amount of undigested IgG and
      F(ab')2 aggregates. CSVAPA contained more than 60% venom-specific antibodies,
      showed moderate complement activation, no IgE contamination, safe level of
      endotoxin, and also showed pre-clinical safety. The immuno cross-reactivity of
      CSVAPA against 14 Viperidae and Elapidae snake venoms of Africa was tested by
      ELISA and immunoblotting, and the neutralization of major enzymatic venom
      activities, demonstrating that high molecular weight (>50 kDa) venom proteins are
      better recognized/neutralized compared to relatively low molecular weight (<20
      kDa) venom proteins. CSVAPA at a dose of 3-12 times higher than the clinical dose
      did not cause deaths or adverse reaction of treated rabbits. The results suggest
      the satisfactory quality, safety, and efficacy of CSVAPA.

PMID- 30189244
TI  - Tetraspanin CD82 represses Sp1-mediated Snail expression and the resultant E
      cadherin expression interrupts nuclear signaling of beta-catenin by increasing
      its membrane localization.
AB  - Tetraspanin membrane proteins form physical complexes with signaling molecules
      and have been suggested to influence the signaling events of associated
      molecules. Of the tetraspanin proteins, CD82 has been shown to promote homotypic
      cell-cell adhesion, which partially accounts for its role in suppressing cancer
      invasion and metastasis. We found here that CD82-induced cell-cell adhesion is
      attributed to increased E-cadherin expression through CD82-mediated
      downregulation of the E-cadherin repressor Snail. The Snail repression by CD82
      resulted from the reduced binding of the Sp1 transcription factor to the Snail
      gene promoter. Notably, high CD82 expression did not allow the fibronectin matrix
      to induce Sp1 phosphorylation, implicating CD82 inhibition of the fibronectin
      integrin signaling-dependent Sp1 activation. Meanwhile, E-cadherin upregulated by
      CD82 pulled beta-catenin up to the membrane region, and consequently reduced the
      amount of cytoplasmic beta-catenin that was able to move into to the nucleus. The
      Wnt signal-induced nuclear translocation of beta-catenin was also inhibited by
      the CD82 function of upregulating E-cadherin. Overall, high CD82 expression was
      likely to suppress fibronectin adhesion-induced Sp1 activation signaling for
      Snail expression, resulting in continuous E-cadherin expression, which
      contributed not only to the maintenance of strong cell-cell adhesion but also to
      the blockage of nuclear beta-catenin signaling.

PMID- 30189245
TI  - Novel cytoskeletal mutations with immunodeficiency: Why is the raven like a
      writing desk?

PMID- 30189246
TI  - Impact of Hematopoietic Stem Cell Transplantation on Dental Development.
AB  - To investigate dental development in patients treated with a hematopoietic stem
      cell transplantation (HSCT), 42 children and young adults who were under 12 years
      old at time of HSCT were examined for dental agenesis, microdontia, and root-to
      crown ratio. Conditioning regimens were total body irradiation (TBI) based in 12
      patients, busulfan based in 21 patients, and 9 patients had other
      chemotherapeutic agents. Sixteen patients were <3 years old, 9 patients were 3 to
      6 years old, and 17 patients were 6 to 12 years old at HSCT. Prevalence of
      agenesis and microdontia of at least 1 permanent tooth were, respectively, 51.3%
      and 46.2% in the study population, and 76.3% had an aberrant root-to-crown ratio.
      All these results were highly different from the prevalence in the healthy
      population. Patients treated before the age of 3 years had more microdontia
      (76.9%) and agenesis (92.3%) compared with patients treated at an older age. In
      the subgroup of patients treated after 6 years, there was more microdontia when
      treated with busulfan (50%) compared with treatment with TBI (0%) (P = .044).
      Patients treated with HSCT had many disturbances in dental development. Age at
      HSCT and possibly also the conditioning regimen used had an effect on their type
      and prevalence. Dental follow-up should be incorporated in the multidisciplinary
      follow-up program of these patients.

PMID- 30189247
TI  - PRMT5 inhibition promotes osteogenic differentiation of mesenchymal stromal cells
      and represses basal interferon stimulated gene expression.
AB  - Protein arginine methyltransferases (PRMTs) catalyze symmetric and asymmetric
      methylation on arginine residues of multiple protein targets including histones
      and have essential roles in organismal development and disease. PRMT5 mediates
      symmetric di-methylation (sDMA) of arginine 2 (H3R2me2s) and arginine 8 on
      histone 3 (H3R8me2s), arginine 3 on histones 2A and 4 (H2A/H4R3me2s) as well as
      several non-histone substrates like Sm proteins. Here, we found that selective
      inhibition of PRMT5 in mesenchymal stromal cells (MSCs) led to a reduction in
      colony forming units (CFUs) and increased osteoblast differentiation. PRMT5
      inhibition blocked global symmetric dimethylation of H3R8 and H4R3 but not on
      H3R2. Genome-wide expression analysis by total RNA sequencing of mesenchymal
      stromal cells undergoing osteogenic differentiation revealed significant
      reduction in the intrinsic expression of several interferon-stimulated genes
      (ISGs) upon PRMT5 inhibition. Effects of PRMT5 inhibition on basal ISG expression
      and osteogenic differentiation was effectively blocked by exogenous activation of
      type I IFN signaling. Together, these results indicate important functions for
      PRMT5 in the regulation of basal interferon gene expression in MSCs and in the
      control of differentiation potential of MSCs during osteogenic differentiation.

PMID- 30189248
TI  - Impact of Chronic Opioid Therapy Risk Reduction Initiatives on Opioid Overdose.
AB  - : We assessed the effects of opioid dose and risk reduction initiatives on opioid
      overdose rates among patients on chronic opioid therapy (COT). Using an
      interrupted time series design, we compared trends in overdose rates. We compared
      patients on COT in settings that implemented a COT dose reduction initiative and
      then a COT risk stratification/monitoring initiative to similar patients on COT
      from control settings. From 2006 to 2014, 31,142 patients on COT (22,673
      intervention, 8,469 control) experienced 311 fatal or nonfatal opioid overdoses.
      In primary analyses, changes in opioid overdose rates among patients on COT did
      not differ significantly between intervention and control settings with the
      implementation of either dose reduction or risk stratification/monitoring. In
      planned secondary analyses, overdose rates decreased significantly (17% per year)
      during the dose reduction initiative among patients on COT in intervention
      settings (relative annual change, 0.83; 95% confidence interval, 0.70-0.99), but
      not in control settings (0.98. 95% confidence interval, 0.70-1.39). We conclude
      that overdose rates among patients on COT were not decreased by risk
      stratification and monitoring initiatives. Results were inconsistent for COT dose
      reduction, with no significant difference between intervention and control
      settings (primary hypothesis test), but a significant decrease in overdose rates
      within the intervention setting during dose reduction (secondary hypothesis
      test). PERSPECTIVE: Risk stratification/monitoring interventions among patients
      on COT did not decrease opioid overdose rates. The effects of COT dose reduction
      on opioid overdose rates were inconsistent. Greater decreases in COT dose, a
      larger control group, or both may have been needed to identify conclusive
      reductions in opioid overdose rates.

PMID- 30189249
TI  - Risk factors for recurrent anaphylaxis-related emergency department visits in the
      United States.
AB  - BACKGROUND: Anaphylaxis is a potentially life-threatening allergic reaction with
      a strong risk of recurrence. OBJECTIVE: To assess risk factors associated with
      recurrent anaphylaxis-related emergency department (ED) visits within 1 year of
      an ED visit for anaphylaxis in a large observational cohort study. METHODS: We
      used an administrative claims database to identify patients seen from 2008
      through 2012 in the ED for anaphylaxis based on an International Classification
      of Diseases, Ninth Revision, Clinical Modification diagnosis code algorithm.
      Patients with at least 2 years of continuous enrollment in a health plan were
      included. Multivariable logistic regression analysis was used to determine
      associations with recurrence of anaphylaxis within 1 year. RESULTS: During the 5
      year study period, 7,367 patients (median age, 42 years; <18 years old, 23.3%)
      met the inclusion criteria. The most common anaphylaxis trigger was unspecified
      (56.2%), followed by food (25.3%), medication (14.6%), and venom (3.9%). Overall,
      3.0% of patients had an additional anaphylaxis-related ED visit within 1 year
      (3.61 episodes per 100 patient-years). On multivariable analysis, risk factors
      associated with anaphylaxis recurrence were food trigger (odds ratio [OR], 2.31;
      95% confidence interval [CI], 1.34-3.99), history of asthma (OR, 1.30; 95% CI,
      1.13-1.51), and intensive care unit admission at the index anaphylaxis event (OR,
      1.95; 95% CI, 1.41-2.69). CONCLUSION: In this contemporary cohort study, history
      of asthma, food trigger, and greater index anaphylaxis severity, as measured by
      intensive care unit admission, were associated with a higher likelihood of a
      recurrent anaphylaxis-related ED visit within 1 year.

PMID- 30189250
TI  - Targeting the paracrine hormone-dependent guanylate
      cyclase/cGMP/phosphodiesterases signaling pathway for colorectal cancer
      prevention.
AB  - Colorectal cancer (CRC) is one of the leading causes of cancer related-deaths.
      The risk of development of CRC is complex and multifactorial, and includes
      disruption of homeostasis of the intestinal epithelial layer mediated though
      dysregulations of tumor suppressing/promoting signaling pathways. Guanylate
      cyclase 2C (GUCY2C), a membrane-bound guanylate cyclase receptor, is present in
      the apical membranes of intestinal epithelial cells and maintains homeostasis.
      GUCY2C is activated upon binding of paracrine hormones (guanylin and uroguanylin)
      that lead to formation of cyclic GMP from GTP and activation of downstream
      signaling pathways that are associated with normal homeostasis.
      Dysregulation/suppression of the GUCY2C-mediated signaling promotes CRC
      tumorigenesis. High-calorie diet-induced obesity is associated with deficiency of
      guanylin expression and silencing of GUCY2C-signaling in colon epithelial cells,
      leading to tumorigenesis. Thus, GUCY2C agonists, such as linaclotide, exhibit
      considerable role in preventing CRC tumorigenesis. However, phosphodiesterases
      (PDEs) are elevated in intestinal epithelial cells during CRC tumorigenesis and
      block GUCY2C-mediated signaling by degrading cyclic GMP to 5'-GMP. PDE5-specific
      inhibitors, such as sildenafil, show considerable anti-tumorigenic potential
      against CRC by amplifying the GUCY2C/cGMP signaling pathway, but cannot achieve
      complete anti-tumorigenic effects. Hence, dual targeting the elevation of cGMP by
      providing paracrine hormone stimuli to GUCY2C and by inhibition of PDEs may be a
      better strategy for CRC prevention than alone. This review delineates the
      involvement of the GUCY2C/cGMP/PDEs signaling pathway in the homeostasis of
      intestinal epithelial cells. Further, the events are associated with
      dysregulation of this pathway during CRC tumorigenesis are also discussed. In
      addition, current updates on targeting the GUCY2C/cGMP/PDEs pathway with GUCY2C
      agonists and PDEs inhibitors for CRC prevention and treatment are described in
      detail.

PMID- 30189251
TI  - A randomized controlled trial comparing the efficacy of topical antibiotic
      steroid combination versus no treatment after fornix-incision strabismus surgery.
AB  - PURPOSE: To compare comfort and inflammation in patients treated with
      postoperative topical antibiotic steroids in one eye versus no treatment in the
      other eye. METHODS: This prospective, randomized single-masked study included all
      patients with planned symmetrical strabismus surgery via fornix incision. One eye
      was randomly assigned to topical postoperative tobramycin-dexamethasone and the
      other eye was not treated. Patient and parent questionnaires were administered,
      and two masked observers assessed conjunctival injection over the muscle and
      wound site. RESULTS: A total of 70 patients completed at least 1 postoperative
      visit and were included. There was no statistically significant difference
      between the treatment eye and the no treatment eye in any of the studied
      parameters. CONCLUSIONS: Postoperative topical antibiotic steroid did not prove
      to be superior to no treatment in uncomplicated fornix surgery with regard to
      patient comfort and inflammation. In those cases, consideration may be given to
      sparing the patient the inconvenience, cost, and potential complications of the
      topical medication.

PMID- 30189252
TI  - Pulmonary arterial hypertension: New pathophysiological insights and emerging
      therapeutic targets.
AB  - Pulmonary arterial hypertension (PAH) encompasses a group of clinical entities
      characterized by sustained vasoconstriction and progressive vascular remodeling
      that act in concert to elevate pulmonary vascular resistance. The current
      treatments for PAH are mainly dedicated to target the process of vasoconstriction
      and do not offer a cure. There is now accumulating evidence that expansion of
      pulmonary artery cells due to increased proliferation and apoptotic evasion is a
      key pathological component of vascular remodeling that occurs in PAH. Thus,
      vascular lesions seen in advanced PAH patients present some cancer-like
      characteristics offering important avenues for exploration and expanding
      treatment options. In this review article, we will discuss recent advances into
      mechanisms underlying disease progression, with a focus on pulmonary artery
      smooth muscle cells.

PMID- 30189253
TI  - TARP syndrome: Long-term survival, anatomic patterns of congenital heart defects,
      differential diagnosis and pathogenetic considerations.
AB  - TARP syndrome (TARPS) is an X-linked syndromic condition including Robin
      sequence, congenital heart defects, developmental delay, feeding difficulties and
      talipes equinovarus, as major features. The disease is caused by inactivating
      mutations in RBM10 which encodes for a RNA binding motif protein involved in
      transcript processing. We herein report a male born from healthy and non
      consanguineous parents, presenting prenatal record of intrauterine fetal growth
      retardation, and postnatal features including growth and developmental delays,
      CNS abnormalities, facial dysmorphisms, bilateral syndactyly at the hands,
      talipes equinovarus and congenital heart defects. By using trio-based Whole Exome
      Sequencing approach, a maternally inherited RBM10 frameshift variant causing
      decay of the RBM10 transcript was identified. Despite the syndrome is considered
      lethal in affected males, our subject with molecularly confirmed TARPS is still
      alive at 11 years of age supporting the chance of surviving. Long-term surviving
      in TARPS is extremely rare and should be considered in genetic counselling and
      clinical follow up of the syndrome. We provide the natural history of the
      syndrome, reviewing the major clinical characteristics. Congenital heart defects
      are confirmed as specific diagnostic markers for the syndrome. In addition,
      cardiac anatomical details are defining a possible clinical overlap with
      syndromic conditions related to the hedgehog pathway and/or primary cilium
      anomalies as Oral-Facial-Digital or Smith-Lemli-Opitz syndromes.

PMID- 30189254
TI  - Peritoneal reimplantation of trophoblastic tissue following laparoscopic
      treatment of ectopic pregnancy: A case report and review of literature.
AB  - Reimplantation of trophoblastic tissue in the abdomen after treatment of an
      ectopic pregnancy is rarely reported but is very likely an underestimated
      complication to laparoscopy. We present a case report and review of the
      literature. A total of 25 cases of reimplantation of trophoblastic tissue
      following laparoscopic removal of ectopic pregnancy (EP) have been reported in
      the period January 1989 to January 2018 including our case. No cases have been
      reported before 1989. The use of salpingostomy vs. salpingectomy as the primary
      treatment of EP prior to the complication is comparable. In approximately half of
      the cases the reimplanted trophoblastic tissue was placed in the peritoneum and
      the rest in the omentum, on the bowel, in the uterosacral ligament and on the
      uterine body. During surgery it is important to remove all pathologic tissue and
      the Trendelenburg position should be considered avoided. Treatment using a single
      dose Methotrexate should be performed when there is a potential risk of retaining
      tissue or if the serum human chorionic gonadotropin (S-hCG) is insufficiently
      decreasing after surgery. All patients treated for an ectopic pregnancy should be
      considered monitored until S-hCG is undetectable.

PMID- 30189255
TI  - Mixed Effect Machine Learning: a framework for predicting longitudinal change in
      hemoglobin A1c.
AB  - Accurate and reliable prediction of clinical progression over time has the
      potential to improve the outcomes of chronic disease. The classical approach to
      analyzing longitudinal data is to use (generalized) linear mixed-effect models
      (GLMM). However, linear parametric models are predicated on assumptions, which
      are often difficult to verify. In contrast, data-driven machine learning methods
      can be applied to derive insight from the raw data without a priori assumptions.
      However, the underlying theory of most machine learning algorithms assume that
      the data is independent and identically distributed, making them inefficient for
      longitudinal supervised learning. In this study, we formulate an analytic
      framework, which integrates the random-effects structure of GLMM into non-linear
      machine learning models capable of exploiting temporal heterogeneous effects,
      sparse and varying-length patient characteristics inherent in longitudinal data.
      We applied the derived mixed-effect machine learning (MEml) framework to predict
      longitudinal change in glycemic control measured by hemoglobin A1c (HbA1c) among
      well controlled adults with type 2 diabetes. Results show that MEml is
      competitive with traditional GLMM, but substantially outperformed standard
      machine learning models that do not account for random-effects. Specifically, the
      accuracy of MEml in predicting glycemic change at the 1st, 2nd, 3rd, and 4th
      clinical visits in advanced was 1.04, 1.08, 1.11, and 1.14 times that of the
      gradient boosted model respectively, with similar results for the other methods.
      To further demonstrate the general applicability of MEml, a series of experiments
      were performed using real publicly available and synthetic data sets for accuracy
      and robustness. These experiments reinforced the superiority of MEml over the
      other methods. Overall, results from this study highlight the importance of
      modeling random-effects in machine learning approaches based on longitudinal
      data. Our MEml method is highly resistant to correlated data, readily accounts
      for random-effects, and predicts change of a longitudinal clinical outcome in
      real-world clinical settings with high accuracy.

PMID- 30189256
TI  - Infection dynamics of Toxoplasma gondii in gut-associated tissues after oral
      infection: The role of Peyer's patches.
AB  - Toxoplasma gondii is a common perorally transmitted parasite; however, its
      immunopathogenesis in gut-associated tissues remains unclear. Here, we compared
      disease manifestation in C57BL/6 immunocompetent wild type (WT) mice and
      immunocompromised interferon (IFN)-gamma-deficient (GKO) mice after peroral
      infection (PI) with T. gondii cysts (Fukaya strain). Strong PI-induced Th1
      cytokine expression was detected in WT mice. Moreover, bradyzoite-specific
      T.g.HSP30/bag1 mRNA was detected in the ileum parenchyma and Peyer's patches
      (PP), but not in the mesenteric lymph nodes, at 7 days post-infection in WT mice,
      and was significantly higher than that in GKO mice. Nested PCR showed that
      parasites existed in ileum parenchyma at days 1 and 1.5 post-PI in GKO and WT
      mice, respectively. In addition, quantitative competitive-PCR indicated that T.
      gondii first colonized the PP (day 3 post-PI), followed by the ileum parenchyma
      and mesenteric lymph nodes, spleen, and portal and aortic blood (day 7 post-PI).
      Although parasites were consistently more abundant in GKO mice, similar invasion
      and dissemination patterns were observed in the two hosts. Collectively, these
      data suggest that some zoites differentiate from tachyzoites to bradyzoites in
      the ileum and that T. gondii initially invades the ileum parenchyma, and then
      accumulates and proliferates in the PP before disseminating through the lymphatic
      systems of both GKO and WT hosts.

PMID- 30189257
TI  - Functional suppression of macrophages derived from THP-1 cells by environmentally
      relevant concentrations of arsenite.
AB  - Environmental exposure to arsenic is known to induce immunotoxicity. Macrophages
      are the professional phagocytes that are important in the immune system. In this
      study, we utilized the macrophages derived from the THP-1 human monocyte cell
      line as the experimental model to study the functional suppression induced by
      arsenite (As+3), one of the most prevalent forms of inorganic arsenic, at
      environmentally-relevant concentrations. Apoptosis was observed in the THP-1
      derived macrophages treated with 500 nM As+3 for 18 h. Suppression of
      phagocytosis was induced by 18 h As+3 treatment starting from 100 nM. Suppressive
      effects on the production of two pro-inflammatory cytokines, IL-1beta and TNF
      alpha, were also found with the treatment of low to moderate doses of As+3 in
      lipopolysaccharides-stimulated THP-1 derived macrophages. The nitric oxide
      production was also inhibited by As+3 treatments, which was negatively correlated
      with the production of superoxide. Collectively, the results from the study
      demonstrated that environmentally-relevant concentrations of As+3 induced
      cytotoxicity and suppressed the major cellular functions in THP-1 derived
      macrophages. The macrophages were showed to be relatively sensitive to As+3, and
      could be the essential target of the toxicity induced by environmental arsenic
      exposures.

PMID- 30189258
TI  - Expression of zona pellucida 3 gene is regulated by 17alpha-ethinylestradiol in
      adult topmouth culter Culter alburnus.
AB  - Estrogen could lead to abnormal modulation or disruption of physical development,
      reproduction and sexual behavior in aquatic wildlife, especially in fish.
      Information on the toxicity of estrogens to native species in that can be used in
      site-specific risk assessments is scarce. In the present study, one zona
      pellucida 3 (ZP3) homologue termed CaZP3 was firstly identified from topmouth
      culter Culter alburnus, following its structural characteristics, tissue
      distribution and transcriptional modulation to 17alpha-ethinylestradiol (EE2)
      exposure were investigated. Meanwhile, vitellogenin (VTG) gene was employed to
      provide a comparison of the reactive ability to EE2 induction. The CaZP3
      characterized with analogical functional domains such as ZP domain, SP, IHP, EHP,
      12 cysteine residues, one N-linked glycosylation site and two conserved O-linked
      glycosylation sites and equal number of eight exons and seven introns with ZP3
      counterparts of higher species. CaZP3 mRNA predominantly expressed in ovary,
      besides, highly expressed in female heart and male muscle and relatively high
      expressed in testis. CaZP3 has the lower reactive ability to EE2 induction in
      comparison with VTG, however, CaZP3 transcripts were significantly induced in
      gonads of both male and female culter by EE2 and could be used as an alternative
      biomarker to monitor EE2 activity. The present results supplement the database
      for toxicity of EE2, especially for fish species endemic to China and provide
      some useful information for the monitoring of EE2 activity in aquatic
      environment.

PMID- 30189259
TI  - Effect of alkyl chain on cellular uptake and antitumor activity of
      hydroxycamptothecin nanoparticles based on amphiphilic linear molecules.
AB  - Drug-loaded nanoparticles utilizing amphiphilic molecules as nanocarriers were
      developed broadly for nanoscale drug delivery system. Linear amphiphilic molecule
      (PEG45C18) based on PEG and alkyl chain was designed and synthesized. To study
      the influence of alkyl chain on antitumor activity, 10-hydroxycamptothecin (HCPT)
      was selected as the hydrophobic drug, amphiphilic molecule (PEG45C18) and
      hydrophilic PEG (PEG45) were applied as nanocarriers to form HCPT-loaded
      nanoparticles (HCPT/PEG45C18 NPs and HCPT/PEG45 NPs). These two nanoparticles
      presented high drug-loading content, stability, but different release manner and
      antitumor efficacy. The HCPT/PEG45C18 NPs existed slower release manner but
      higher antitumor activity than HCPT/PEG45 NPs, IC50 value was decreased
      approximately 8.5-fold against 4T1 cells in vitro. Moreover, the antitumor
      efficacy of HCPT/PEG45C18 NPs on 4T1-bearing mice was promoted significantly, the
      inhibition rate based on average tumor weight was 1.5-fold higher than HCPT/PEG45
      NPs, besides, HCPT/PEG45C18 NPs exhibited better tumor accumulation than
      HCPT/PEG45 NPs. These results suggested alkyl chain affect the antitumor activity
      significantly due to nanoparticles decorated with alkyl chains existing higher
      endocytosis efficacy to cells. According to the enhanced antitumor efficacy, it
      was suggested that HCPT/PEG45C18 NPs showed the potential application for cancer
      therapy in clinic, and alkyl chains should be considered for designing
      biomaterials.

PMID- 30189260
TI  - Delay in Oral Feeding is Associated With a Decrease in Anastomotic Leak Following
      Transhiatal Esophagectomy.
AB  - The cervical anastomotic leak is a major complication of transhiatal
      esophagectomy and results in chronic strictures in up to half of patients. A
      change in postoperative protocol to delaying initiation of oral intake was made
      with the goal of reducing anastomotic leak rate and associated sequelae. A
      postoperative protocol change was applied to all patients undergoing elective
      transhiatal esophagectomy. Rate of anastomotic leak and anastomotic stricture,
      defined as defect in the esophagogastric anastomosis and narrowing of the
      anastomosis, respectively, were compared between pre- and post-change groups.
      Between 2004 and 2013, 203 patients underwent transhiatal esophagectomy with
      cervical anastomosis. Historically, oral intake was resumed on postoperative day
      3, and during the course of the study, a change was made to the protocol to delay
      oral intake until 15 days postoperatively. Eighty-three patients were in the
      early oral feeding group (postoperative day 3), and 120 were in the delayed oral
      intake group (postoperative day 15). There was a statistically significant
      decrease in the rate of anastomotic leak from 14.5% to 4.2% between the early and
      delayed intake groups, respectively (P = 0.0089). There was also a trend (P =
      0.05) towards a lower rate of anastomotic stricture in all patients in the
      delayed intake group (15.8%) compared with those in the early feeding group
      (27.7%). By increasing the time to postoperative oral feeding, we have noted an
      associated improvement in both immediate and long-term outcomes of elective
      transhiatal esophagectomy patients.

PMID- 30189261
TI  - Three-Patch Aortic Root Reconstruction With Extended Left Main Coronary Artery
      Patch Augmentation in Neonates and Infants.
AB  - Left main coronary artery (LMCA) stenosis is present in approximately 5% of
      patients with congenital supravalvular aortic stenosis (SVAS) (Fig. 1)1 and is
      associated with an increased risk of sudden cardiac death.2 However, patients
      undergoing coronary artery intervention at the time of SVAS repair are at the
      highest risk of experiencing major adverse cardiac events.3 Literature reports of
      surgical techniques and outcomes of concomitant coronary artery repair in these
      high-risk patients are diverse and inconsistently described. We have recently
      adopted a standardized surgical technique for management of this complex
      pathology by combining extended LMCA patch augmentation with a 3-patch aortic
      root reconstruction (Brom's technique). In this report, we describe our
      contemporary surgical technique of 3-patch aortic root reconstruction with
      extended LMCA patch augmentation for patients with congenital SVAS with ostial
      LMCA stenosis and bilateral outflow tract obstruction. Institutional review board
      approval was obtained for retrospective review of patient charts.

PMID- 30189262
TI  - Hippocampal granule cell loss in human chronic alcohol abusers.
AB  - Chronic alcohol abuse causes cognitive impairments associated with
      neurodegeneration and volume loss in the human hippocampus. Here, we hypothesize
      that alcohol reduces the number of granule cells in the human dentate gyrus and
      consequently contribute to the observed volume loss. Hippocampal samples were
      isolated from deceased donors with a history of chronic alcohol abuse and from
      controls with no alcohol overconsumption. From each case, a sample from the mid
      portion of hippocampus was sectioned, immunostained for the neuronal nuclear
      marker NeuN, and counter stained with hematoxylin. Granule cell number and volume
      of granular cell layer in the dentate gyrus were estimated using stereology. We
      found a substantial reduction in granule cell number and also a significantly
      reduced volume of the granular cell layer of chronic alcohol abusers as compared
      to controls. In controls there was a slight age-related decline in the number of
      granule cells and volume of granular cell layer in line with previous studies.
      This was not observed among the alcoholics, possibly due to a larger impact of
      alcohol abuse than age on the degenerative changes in the dentate gyrus. Loss of
      neurons in the alcoholic group could either be explained by an increase of cell
      death or a reduced number of new cells added to the granular cell layer. However,
      there is no firm evidence for an increased neuronal death by chronic alcohol
      exposure, whereas a growing body of experimental data indicates that neurogenesis
      is impaired by alcohol. In a recent study, we reported that alcoholics show a
      reduced number of stem/progenitor cells and immature neurons in the dentate
      gyrus, hence that alcohol negatively affects hippocampal neurogenesis. The
      present results further suggest that such impairment of neurogenesis by chronic
      alcohol abuse also results in a net loss of granule cells in the dentate gyrus of
      hippocampus.

PMID- 30189263
TI  - Pedunculopontine nucleus: An integrative view with implications on Deep Brain
      Stimulation.
AB  - The pedunculopontine nucleus (PPN) is a reticular nucleus located in the
      mesencephalic and upper pontine tegmentum. Initially, characterized by its
      predominant cholinergic projection neurons, it was associated with the
      "mesencephalic locomotor region" and "reticular activating system". Furthermore,
      based on histopathological studies, the PPN was hypothesized to play a role in
      the manifestation of symptoms in movement disorders such as Parkinson's disease
      (PD). Since axial symptoms represent unmet needs of PD treatments, a series of
      pioneering experiments in Parkinsonian monkeys promoted the idea of a potential
      new target for deep brain stimulation (DBS) and much clinical interest was
      generated in the following years leading to a number of trials analysing the role
      of PPN for gait disorders. This review summarizes the historical background and
      more recent findings about the anatomy and function of the PPN and its
      implications in the basal ganglia network of the normal as well as diseased
      brain. Classical views on PPN function shall be challenged by more recent
      findings. Additionally, the current role and future perspectives of PPN DBS in PD
      patients shall be outlined.

PMID- 30189264
TI  - Role of hypochlorous acid (HOCl) and other inflammatory mediators in the
      induction of macrophage extracellular trap formation.
AB  - The infiltration of activated leukocytes, including macrophages, at sites of
      inflammation and the formation and presence of hypochlorous acid (HOCl) are
      interlinked hallmarks of many debilitating disease processes, including
      atherosclerosis, arthritis, neurological and renal disease, diabetes and obesity.
      The production of extracellular traps by activated leukocytes in response to a
      range of inflammatory stimuli is increasingly recognised as an important process
      within a range of disease settings. We show that exposure of human monocyte
      derived macrophages to pathophysiological levels of HOCl results in the dose
      dependent extrusion of DNA and histones into the cellular supernatant, consistent
      with extracellular trap formation. Concurrent with, but independent of these
      findings, macrophage exposure to HOCl also resulted in an immediate and sustained
      cytosolic accumulation of Ca2+, culminating in the increased production of
      cytokines and chemokines. Polarisation of the macrophages prior to HOCl exposure
      revealed a greater propensity for inflammatory M1 macrophages to produce
      extracellular traps, whereas alternatively-activated M2 macrophages were less
      susceptible to HOCl insult. M1 macrophages also produced extracellular traps on
      exposure to phorbol myristate acetate (PMA), interleukin-8 (IL-8) and tumour
      necrosis factor alpha (TNFalpha). Taken together, these data indicate a potential
      role for macrophages in mediating extracellular trap formation, which may be
      relevant in pathological conditions characterised by chronic inflammation or
      excessive HOCl formation.

PMID- 30189265
TI  - NADPH oxidases in bone homeostasis and osteoporosis.
AB  - Bone is a tissue with constant remodeling, where osteoblasts form and osteoclasts
      degrade bone. Both cell types are highly specialized in their function and both
      form from precursors and have to be replaced on a regular basis. This replacement
      represents one control level of bone homeostasis. The second important level
      would be the control of the function of osteoblasts and osteoclasts in order to
      keep the balance of bone -formation and -degradation. Both differentiation and
      control of cellular function are potentially redox sensitive processes. In fact,
      reactive oxygen species (ROS) are utilized by a wide range of cells for
      differentiation and control of cellular signaling and function. A major source of
      ROS is the family of NADPH oxidases. The sole function of those enzymes is the
      formation of ROS in a controlled and targeted manner. Importantly the members of
      the NADPH oxidase family differ in their localization and in the type and amount
      of ROS produced. Accordingly the impact of the members of the NADPH oxidase
      family on differentiation and function differs between cell types. This review
      will highlight the function of different NADPH oxidases in differentiation and
      function of bone cells and thereby will discuss the role of NADPH oxidases in
      bone homeostasis and osteoporosis.

PMID- 30189266
TI  - Circadian control of BDNF-mediated Nrf2 activation in astrocytes protects
      dopaminergic neurons from ferroptosis.
AB  - Astrocyte-neuron interactions protect neurons from iron-mediated toxicity. As
      dopamine can be metabolized to reactive quinones, dopaminergic neurons are
      susceptible to oxidative damage and ferroptosis-like induced cell death.
      Detoxification enzymes are required to protect neurons. Brain-derived
      neurotrophic factor (BDNF) plays a key role in the regulation of redox sensitive
      transcription factor Nrf2 in astrocytes and metabolic cooperation between
      astrocytes and neurons. This article reviews the importance of BDNF and astrocyte
      neuron interactions in the protection of neurons against oxidative damages in
      rodent brains. We previously proposed that BDNF activates Nrf2 via the truncated
      TrkB.T1 and p75NTR receptor complex in astrocytes. Stimulation by BDNF generates
      the signaling molecule ceramide, which activates PKCzeta leading to induction of
      the CK2-Nrf2 signaling axis. As a cell clock regulates p75NTR expression, we
      suggested that BDNF effectively activates Nrf2 in astrocytes during the rest
      phase. In contrast, neurons express both TrkB.FL and TrkB.T1, and TrkB.FL
      tyrosine kinase activity inhibits p75NTR-dependent ceramide generation and
      internalizes p75NTR. Therefore, BDNF may not effectively activate Nrf2 in
      neurons. Notably, neurons only weakly activate detoxification and antioxidant
      enzymes/proteins via the Nrf2-ARE signaling axis. Thus, astrocytes may provide
      relevant transcripts and/or proteins to neurons via microparticles/exosomes
      increasing neuronal resistance to oxidative stress. Circadian increases in the
      levels of circulating glucocorticoids may further facilitate material transfer
      from astrocytes to neurons via the stimulation of pannexin 1 channels-P2X7R
      signaling pathway in astrocytes at the beginning of the active phase.
      Dysregulation of astrocyte-neuron interactions could therefore contribute to the
      pathogenesis of neurodegenerative diseases including Parkinson's disease.

PMID- 30189267
TI  - Intronic miRNA mediated gene expression regulation controls protein crowding
      inside the cell.
AB  - Gene regulatory effects of microRNAs at a posttranscriptional level have been
      established over the last decade. In this study, we analyze the interaction
      networks of mRNA translation regulation through intronic miRNA, under various
      tissue-specific cellular contexts, taking into account the thermodynamic
      affinity, chemical kinetics, co-localization, concentration levels, network
      parameters and the presence of competitive interactors. This database, and
      analysis has been made available through an open-access web-server, miRiam, to
      promote further exploration. Here we report that expression of genes involved in
      Apoptosis Processes, Immune System Processes, Translation Regulator Activities,
      and Molecular Transport Activities within the cell are predominately regulated by
      miRNA mediation. Our findings further indicate that this regulatory effect has a
      profound effect in controlling protein crowding inside the cell. A miRNA mediated
      gene expression regulation serves as a temporal regulator, allowing the cellular
      machinery to temporarily 'pause' the translation of mRNA, indicating that the
      miRNA-mRNA interactions may be important for governing the optimal usage of cell
      volume.

PMID- 30189270
TI  - Orally inhaled migraine therapy: Where are we now?
AB  - Migraine is a debilitating disease that affects 9% of men and 19% of women
      worldwide with high socio-economic and personal impact. Surveys indicate that
      migraineurs are among the most dissatisfied with available therapeutic options,
      predominantly given via oral or injectable routes, citing side effects as the
      primary complaint. Orally inhaled therapies have the potential to offer faster
      onset of action with fewer side effects compared to existing therapies, yet
      development has stalled. Despite emerging therapies such as calcitonin gene
      related peptide antagonists, there are still good opportunities for repositioning
      migraine drugs via the inhaled route.

PMID- 30189269
TI  - Role of Kruppel homolog 1 (Kr-h1) in methyl farnesoate-mediated vitellogenesis in
      the swimming crab Portunus trituberculatus.
AB  - Similar to the role of juvenile hormone (JH) in insects, methyl farnesoate (MF),
      the unepoxidized form of JH III, regulates many developmental processes in
      crustaceans, such as molting and reproduction. We have previously showed that the
      JH receptor, Methoprene-tolerant (Met), which is also a candidate receptor for
      MF, might be involved in the MF-mediated vitellogenesis in the swimming crab
      Portunus trituberculatus. In this study, the role of Kruppel homolog 1 (Kr-h1), a
      transcription factor downstream Met in JH signaling, was further investigated.
      The deduced protein of Pt-Kr-h1 contained seven repeats of zinc finger motifs,
      similar to Kr-h1s from other crustacean species, but differing from the eight
      zinc finger motifs found in insect Kr-h1s. MF treatment in vitro induced the
      expression of Pt-Kr-h1 in hepatopancreas but not ovary, which is similar to the
      MF-responsive pattern of Pt-Met as previously reported. Moreover, the expression
      of Pt-Kr-h1 decreased significantly after treating with Pt-Met dsRNA, strongly
      indicating that the Pt-Kr-h1 might be involved in the Met-mediated MF signaling
      pathway. RNAi of Pt-Met and Pt-Kr-h1 both led to a decrease in vitellogenin (Vg)
      expression, and the reduction cannot be rescued by adding MF, suggesting the
      regulation of vitellogenesis by MF may act through Met and Kr-h1. These results
      would help to enhance the current understanding of the regulatory mechanism of MF
      signaling, and provide a vital resource for further research into the evolution
      of hormonal pathways in arthropods.

PMID- 30189271
TI  - The potential to treat lung cancer via inhalation of repurposed drugs.
AB  - Lung cancer is a highly invasive and prevalent disease with ineffective first
      line treatment and remains the leading cause of cancer death in men and women.
      Despite the improvements in diagnosis and therapy, the prognosis and outcome of
      lung cancer patients is still poor. This could be associated with the lack of
      effective first-line oncology drugs, formation of resistant tumors and non
      optimal administration route. Therefore, the repurposing of existing drugs
      currently used for different indications and the introduction of a different
      method of drug administration could be investigated as an alternative to improve
      lung cancer therapy. This review describes the rationale and development of
      repositioning of drugs for lung cancer treatment with emphasis on inhalation. The
      review includes the current progress of repurposing non-cancer drugs, as well as
      current chemotherapeutics for lung malignancies via inhalation. Several potential
      non-cancer drugs such as statins, itraconazole and clarithromycin, that have
      demonstrated preclinical anti-cancer activity, are also presented. Furthermore,
      the potential challenges and limitations that might hamper the clinical
      translation of repurposed oncology drugs are described.

PMID- 30189272
TI  - Corrigendum to 'Current state and challenges in developing oral vaccines' [Adv.
      Drug Deliv. Rev. 114 (2017) 116-131].

PMID- 30189273
TI  - Physiologically based pharmacokinetic modelling to guide drug delivery in older
      people.
AB  - Older patients are generally not included in Phase 1 clinical trials despite
      being the population group who use the largest number of prescription medicines.
      Physiologically based pharmacokinetic (PBPK) modelling provides an understanding
      of the absorption and disposition of drugs in older patients. In this review,
      PBPK models used for the prediction of absorption and exposure of drugs after
      parenteral, oral and transdermal administration are discussed. Comparisons
      between predicted drug pharmacokinetics (PK) and observed PK are presented to
      illustrate the accuracy of the predictions by the PBPK models and their potential
      use in informing clinical trial design and dosage adjustments in older patients.
      In addition, a case of PBPK modelling of a bioequivalence study on two controlled
      release products is described, where PBPK predictions reproduced the study
      showing bioequivalence in healthy volunteers but not in older subjects with
      achlorhydria, indicating further utility in prospectively identifying challenges
      in bioequivalence studies.

PMID- 30189268
TI  - High-throughput gene expression analysis identifies p53-dependent and 
      independent pathways contributing to the adrenocortical dysplasia (acd)
      phenotype.
AB  - In mammalian cells TPP1, encoded by the Acd gene, is a key component of the
      shelterin complex, which is required for telomere length maintenance and telomere
      protection. In mice, a hypomorphic mutation in Acd causes the adrenocortical
      dysplasia (acd) phenotype, which includes limb and body axis anomalies, and
      perinatal lethality. p53 deficiency partially rescues limb and body axis
      anomalies in acd mutant embryos, but not perinatal lethality, implicating p53
      independent mechanisms in the acd phenotype. Loss of function of most shelterin
      proteins results in early embryonic lethality. Thus, study of the hypomorphic acd
      allele provides a unique opportunity to understand telomere dysfunction at an
      organismal level. The aim of this study was to identify transcriptome alterations
      in acd mutant and acd, p53 double mutant embryos to understand the p53-dependent
      and -independent factors that contribute to the mutant phenotypes in the context
      of the whole organism. Genes involved in developmental processes, cell cycle,
      metabolic pathways, tight junctions, axon guidance and signaling pathways were
      regulated by p53-driven mechanisms in acd mutant embryos, while genes functioning
      in immune response, and RNA processing were altered independently of p53 in acd,
      p53 double mutant embryos. To our best of knowledge, this is the first study
      revealing detailed transcriptomic alterations, reflecting novel p53-dependent and
      -independent pathways contributing to the acd phenotype. Our data confirm the
      importance of cell cycle and DNA repair pathways, and suggest novel links between
      telomere dysfunction and immune system regulation and the splicing machinery.
      Given the broad applicability of telomere maintenance in growth, development, and
      genome stability, our data will also provide a rich resource for others studying
      telomere maintenance and DNA damage responses in mammalian model systems.

PMID- 30189274
TI  - Preparation of antibacterial poly(lactide)/poly(butylene adipate-co
      terephthalate) composite films incorporated with grapefruit seed extract.
AB  - Antimicrobial poly(lactide) (PLA)/poly(butylene adipate-co-terephthalate) (PBAT)
      blend films incorporated with grapefruit seed extract (GSE) were prepared using a
      solvent casting method. Effect of GSE on the morphological, water vapor barrier,
      thermostability, color, optical, and antimicrobial properties of PLA/PBAT
      composite films was investigated. The composite films showed a yellowish tint
      after incorporation of GSE and exhibited a high UV-light barrier property.
      Incorporation of GSE increased the flexibility and tensile strength of the
      composite films. Films incorporated with 7 wt% of GSE exhibited potent
      antibacterial activity against Listeria monocytogenes, but they showed only
      bacteriostatic activity against Escherichia coli. The PLA/PBAT-GSE composite film
      with UV-light barrier and antibacterial properties has a high potential for an
      active food packaging application.

PMID- 30189275
TI  - Coumarin derivatives as promising xanthine oxidase inhibitors.
AB  - Xanthine oxidase (XO) is an interesting target for the synergic treatment of
      several diseases. Coumarin scaffold plays an important role in the design of
      efficient and potent inhibitors. In the current work, twenty 3-arylcoumarins and
      eight 3-heteroarylcoumarins were evaluated for their ability to inhibit XO. Among
      all the candidates, 5,7-dihydroxy-3-(3'-hydroxyphenyl)coumarin (compound 20)
      proved to be the best inhibitor with an IC50 of 2.13 MUM, being 7-fold better
      than the reference compound, allopurinol (IC50 = 14.75 MUM). To deeply understand
      the potential of this compound, the inhibition mode was also evaluated. Compound
      20 showed an uncompetitive profile of inhibition. Molecular docking studies were
      carried out to analyze the interaction of compound 20 with the studied enzyme.
      The binding mode involving residues different from the catalytic site of the
      binding pocket, is compatible to the observed uncompetitive inhibition. Compound
      20 was not cytotoxic at its IC50 value, as demonstrated by the viability of 99.1%
      in 3 T3 cells. Furthermore, pharmacokinetics and physicochemical properties were
      also calculated, which corroborated with the potential of the studied compounds
      as promising XO inhibitors.

PMID- 30189276
TI  - Adaptively differential expression analysis in gill of Chinese mitten crabs
      (Eriocheir japonica sinensis) associated with salinity changes.
AB  - Desalination of marine species has become an important development direction for
      aquaculture in China and other countries. However, that how to regulate the salt
      balance to adapt to new freshwater habitats is a serious challenge for marine
      species in desalination of aquaculture. In the study, Chinese mitten crabs
      (Eriocheir japonica sinensis) was selected to analyse the adaptively differential
      expression in salinity changes for their novel characteristics of life history.
      The results showed that gill was the most relevant tissue in osmoregulation that
      was validated by biomarkers (Na+/K+-ATP, V-type H+-ATPase) with qPCR. Na+/K+
      ATPase is a primary transporter and maintains the body fluid osmolality by
      actively pumping Na+ to the hemolymph, and V-type H+-ATPase is responsible for
      acid-base balance and nitrogen excretion. So both transcriptome data and qPCR
      results showed the significantly differential expression of Na+/K+-ATPase and V
      type H+-ATPase in gills. Moreover, NAK-alpha had the most significantly
      differential expression level in salinity change, and other genes such as GST,
      HSP90, S27, UBE, VATB also revealed significantly up-regulation. They are
      considered the key enzymes during the transition from a marine environment to
      land. Present results have provided a foundation to further understand the
      molecular adaptive mechanism in desalination of marine species.

PMID- 30189277
TI  - Structural and conformational characterization of linear O-acetyl-glucomannan
      purified from gel of Aloe barbadensis Miller.
AB  - Aloe barbadensis Miller (Aloe vera) is a kind of popular medicinal and
      horticultural crops widely cultivated around the world. Polysaccharides with
      different structural features and bioactivities have been isolated from the pulp
      of Aloe vera. In the current study, a novel polysaccharide fraction (AGP40)
      isolated and purified from gel juice of Aloe vera was subjected to structural and
      conformational analysis. AGP40 had a backbone consisting of major ->4)-beta-Manp
      (1 -> residues and minor ->3)-beta-Manp-(1 -> and ->4)-beta-Glcp-(1 -> residues.
      Low degree of branches distributed at O-6 of 4-linked mannose in the main chain.
      The acetyl groups in AGP40 presented as mono- or di-substituents (O-2, O-3, O-6,
      O-2,3, O-2,6 and O-3,6). AGP40 performed as random coil conformation in 0.1 M
      NaNO3 solution, and had fibrous filaments and irregular spherical structures in
      solid state. Detailed structural and conformational analysis of AGP40 in the
      present study may greatly improve the bioactive function investigation and
      mechanism explanation of acetyl glucomannans in the future.

PMID- 30189278
TI  - Recent progress in the utilization of biosynthesized polyhydroxyalkanoates for
      biomedical applications - Review.
AB  - PHAs (polyhydroxyalkanoates) have emerged as biodegradable plastics more strongly
      in the 20th century. A wide range of bacterial species along with fungi, plants,
      oilseed crops and carbon sources have been used extensively to synthesize PHA on
      large scales. Alteration of PHA monomers in their structures and composition has
      led to the development of biodegradable and biocompatible polymers with highly
      specific mechanical properties. This leads to the incorporation of PHA in
      numerous biomedical applications within the previous decade. PHAs have been
      fabricated in various forms to perform tissue engineering to repair liver, bone,
      cartilage, heart tissues, cardiovascular tissues, bone marrow, and to act as drug
      delivery system and nerve conduits. A large number of animal trials have been
      carried out to assess the biomedical properties of PHA monomers, which also
      confirms the high compatibility of PHA family for this field. This review
      summarizes the synthesis of PHA from different sources, and biosynthetic pathways
      and biomedical applications of biosynthesized polyhydroxyalkanoates.

PMID- 30189279
TI  - Antibacterial hop extracts encapsulated in nanochitosan matrices.
AB  - Hops and the components extracted from them are well known antibacterial agents
      used in beers and as food preservatives, in formulations for topical applications
      on their own or together with other antimicrobial agents, in hormone replacement
      therapy, as antioxidants, tumor development antagonists, and angiogenesis
      inhibitors. Their shortcomings: very low bioavailability, bitter taste, and
      susceptibility to oxidative decomposition have limited their applications. We
      propose nanosized chitosan, an inexpensive, readily available biopolymer with a
      broad spectrum of antibacterial activity, as carrier for lupulone (L) and
      xanthohumol (X), two components of hops. Chitosan nanoparticles (CNP) and
      chitosan-based nanocomposites encapsulating lupulone (CNL) and xanthohumol (CNX)
      were prepared by ionotropic gelation using sodium tripolyphosphate (TPP) as
      crosslinker. Different preparative ratios and conditions were investigated and
      the nanoparticles obtained were characterized by FTIR, colloidal titration, size,
      zeta potential, and antimicrobial activity. The kinetics of the release of L/X
      from composites was studied in vitro. All the nanoparticles were active against
      several Gram-positive, Gram-negative, and Candida strains. Synergistic
      interactions were observed in all cases, although hops are known mainly for their
      activity against Gram-positive bacteria. All nanoparticles showed good stability
      over several months.

PMID- 30189280
TI  - Development of nanocomposite scaffolds based on biomineralization of N,O
      carboxymethyl chitosan/fucoidan conjugates for bone tissue engineering.
AB  - Bone tissue engineering holds great promise and clinical efficacy for the
      regeneration of bone defects. In this study, an amphoteric N,O-carboxymethyl
      chitosan (NOCC) and fucoidan (FD) were covalently cross-linked via an amidation
      reaction to synthesize NOCC/FD composite hydrogels. The hydrogels were
      lyophilized and then three-dimensional scaffolds with interconnected macropores
      were obtained. To enhance the mechanical properties and osteogenic activity, the
      NOCC/FD scaffolds were biomineralized for the growth of hydroxyapatite crystals.
      A comparative assessment of the structures, morphologies, and physical properties
      of the original and mineralized scaffolds were performed by SEM, EDS, X-ray
      diffraction and FT-IR analysis. FD regulated the growth of hydroxyapatite
      nanocrystallites (n-HAp) and thus the NOCC/FD scaffolds showed better
      mineralization efficiency than NOCC scaffolds. The compressive strength of the
      scaffolds was greatly enhanced after mineralization with n-HAp. The n-HAp/NOCC/FD
      scaffolds enhanced the proliferation, ALP activity, and mineralization of
      osteoblast cells more strongly than the original and mineralized NOCC scaffolds.
      Hence, the n-HAp-mineralized NOCC/FD scaffolds may prove to be an excellent and
      versatile scaffold for bone tissue engineering.

PMID- 30189281
TI  - A Randomized Trial Comparing Bilateral Lateral Rectus Recession versus Unilateral
      Recess and Resect for Basic-Type Intermittent Exotropia.
AB  - PURPOSE: To compare long-term outcomes after bilateral lateral rectus recession
      (BLRc) or unilateral lateral rectus recession combined with medial rectus
      resection in the same eye (R&R) for primary treatment of childhood intermittent
      exotropia (IXT). DESIGN: Multicenter, randomized clinical trial. PARTICIPANTS:
      One hundred ninety-seven children 3 to younger than 11 years of age with basic
      type IXT, a largest deviation by prism and alternate cover test at any distance
      of 15 to 40 prism diopters (PD), and near stereoacuity of at least 400 seconds of
      arc. METHODS: Random assignment to BLRc or R&R and masked examinations conducted
      every 6 months after surgery for 3 years. MAIN OUTCOME MEASURES: Proportion of
      participants meeting suboptimal surgical outcome by 3 years, defined as: (1)
      exotropia of 10 PD or more at distance or near using simultaneous prism and cover
      test (SPCT); or (2) constant esotropia of 6 PD or more at distance or near using
      SPCT; (3) loss of 2 octaves or more of stereoacuity from baseline, at any masked
      examination; or (4) reoperation without meeting any of these criteria. RESULTS:
      Cumulative probability of suboptimal surgical outcome by 3 years was 46% (43/101)
      in the BLRc group versus 37% (33/96) in the R&R group (treatment group difference
      of BLRc minus R&R, 9%; 95% confidence interval [CI], -6% to 23%). Reoperation by
      3 years occurred in 9 participants (10%) in the BLRc group (8 of 9 met suboptimal
      surgical outcome criteria) and in 4 participants (5%) in the R&R group (3 of 4
      met suboptimal surgical outcome criteria; treatment group difference of BLRc
      minus R&R, 5%; 95% CI, -2% to 13%). Among participants completing the 3-year
      visit, 29% (25 of 86) in the BLRc group and 17% (13 of 77) in the R&R group
      underwent reoperation or met suboptimal surgical outcome criteria at 3 years
      (treatment group difference of BLRc minus R&R, 12%; 95% CI, -1% to 25%).
      CONCLUSIONS: We did not find a statistically significant difference in suboptimal
      surgical outcome by 3 years between children with IXT treated with BLRc compared
      with those treated with R&R. Based on these findings, we are unable to recommend
      one surgical approach over the other for childhood IXT.

PMID- 30189282
TI  - Macular Morphology and Visual Acuity in Year Five of the Comparison of Age
      related Macular Degeneration Treatments Trials.
AB  - PURPOSE: To evaluate associations of morphologic features with 5-year visual
      acuity (VA) in the Comparison of Age-related Macular Degeneration Treatments
      Trials (CATT). DESIGN: Cohort study within a randomized clinical trial.
      PARTICIPANTS: Participants in CATT. METHODS: Eyes with age-related macular
      degeneration-associated choroidal neovascularization (CNV) and VA between 20/25
      and 20/320 were eligible. Treatment was assigned randomly to ranibizumab or
      bevacizumab and to 3 dosing regimens for 2 years and was at the ophthalmologists'
      discretion thereafter. MAIN OUTCOME MEASURES: Visual acuity, thickness and
      morphologic features on OCT, and lesion size and foveal composition on fundus
      photography (FP) and fluorescein angiography (FA). RESULTS: Visual acuity and
      image gradings were available for 523 of 914 participants (57%) alive at 5 years.
      At 5 years, 60% of eyes had intraretinal fluid (IRF), 38% had subretinal fluid
      (SRF), 36% had subretinal pigment epithelium (RPE) fluid, and 66% had subretinal
      hyper-reflective material (SHRM). Mean (standard deviation) foveal center
      thickness was 148 MUm (99) for retina, 5 MUm (21) for SRF, 125 MUm (107) for
      subretinal tissue complex, 11 MUm (33) for SHRM, and 103 MUm (95) for RPE + RPE
      elevation. The SHRM, thinner retina, greater CNV lesion area, and foveal center
      pathology (all P < 0.001) and IRF (P < 0.05) were independently associated with
      worse VA. Adjusted mean VA letters were 62 for no pathology in the foveal center;
      61 for CNV, fluid, or hemorrhage; 65 for non-geographic atrophy (GA); 64 for
      nonfibrotic scar; 53 for GA; and 56 for fibrotic scar. Incidence or worsening of
      8 pathologic features (foveal GA, foveal scar, foveal CNV, SHRM, foveal IRF,
      retinal thinning, CNV lesion area, and GA area) between years 2 and 5 was
      independently associated with greater loss of VA from years 2 to 5 and VA loss
      from baseline to year 5. CONCLUSIONS: Associations between VA and morphologic
      features previously identified through year 1 were maintained or strengthened at
      year 5. New foveal scar, CNV, intraretinal fluid, SHRM and retinal thinning,
      development or worsening of foveal GA, and increased lesion size are important
      contributors to the VA decline from years 2 to 5. A significant need to develop
      therapies to address these adverse pathologic features remains.

PMID- 30189283
TI  - Ensuring signal quality of cerebral near infrared spectroscopy during continuous
      longterm monitoring.
AB  - BACKGROUND: Near infrared spectroscopy (NIRS) derived hemoglobin difference (HbD:
      oxygenated [HbO2] - reduced hemoglobin [Hb]) and total hemoglobin (HbT: HbO2+Hb)
      have been used as surrogate measures of cerebral blood flow and volume,
      respectively. Statistically, a lack of HbD-blood pressure (BP) or negative HbT-BP
      association is regarded as a state of intact cerebral pressure autoregulation
      (CPA). In contrast, a co-variation of HbD/HbT and systemic blood pressure (BP) in
      the same direction is thought of as a failure of CPA. If the quality of one
      (NIRS/BP) or both signals is compromised, the reliability of the results may be
      adversely affected. In this work, we develop an analytic approach to assess the
      quality of the NIRS signals. NEW METHOD: Given that cardiac pulses cause
      hemodynamic changes that are transmitted through the peripheral vasculature,
      cerebral NIRS signals should exhibit cyclical changes at the pulse frequency.
      Therefore, we propose that an association between HbD/HbT and electrocardiogram
      (EKG) signals would be an indicator of NIRS quality. We demonstrate the
      application of this approach with data collected from six newborns undergoing
      therapeutic hypothermia for neonatal encephalopathy. RESULTS: We observed an
      intermittent lack of association between NIRS signals and EKG data over the
      course of several hours of continuous records, indicating a loss in the strength
      in NIRS signals. COMPARISON WITH EXISTING METHOD: Existing CPA characterization
      suffers from Type-II error which the current preprocessing approach can mitigate.
      CONCLUSIONS: The proposed approach will allow for real-time assessment of NIRS
      signal quality that is essential for accurate CPA monitoring.

PMID- 30189285
TI  - Comparison of statistical tests in effective connectivity analysis of ECoG data.
AB  - BACKGROUND: The effects of statistical testing on the results of multivariate
      autoregressive (MVAR)-based effective connectivity analysis have not been
      adequately investigated, and it is still unclear which statistical test can
      provide the most accurate results. NEW METHODS: Using simulated and real
      electrocorticographic (ECoG) data, we investigated the performance of three
      nonparametric statistical tests - Monte Carlo permutation, bootstrap resampling,
      and surrogate data method in MVAR-based effective connectivity analysis. Receiver
      operating characteristic (ROC) analysis and area under the ROC curve (AUC) were
      used to assess the performance of each statistical test method. In addition, we
      found optimal p-values for each method based on ROC analysis. Finally, we
      investigated the application of statistical tests on partial directed coherence
      analysis of ECoG data collected in a patient with epilepsy. RESULTS: The
      bootstrap statistical test performed more accurately than other methods. The
      surrogate method slightly outperformed the Monte Carlo permutation method.
      Optimal p-values of statistical tests depended on signal-to-noise ratio (SNR) of
      data, and its value increased by reducing SNR of data. By considering the typical
      SNR range of electrophysiological data, we recommended an optimal p-value range
      for the application of each statistical test method. COMPARISON WITH EXISTING
      METHODS: Limited studies have investigated the performance of statistical tests
      for MVAR-based effective connectivity analysis. For the first time, we have
      investigated the effects of baseline connections on the various performances of
      statistical tests. CONCLUSIONS: We recommend utilizing the bootstrap statistical
      test with p-value between 0.05 and 0.1 for effective connectivity analysis of
      ECoG data.

PMID- 30189287
TI  - Differences in the temporal processing between identification and categorization
      of durations: A behavioral and ERP study.
AB  - This study examined how different forms of decision-making modulate time
      perception. Participants performed temporal bisection and generalization tasks,
      requiring them to either categorize a stimulus duration as more similar to short
      or long standards (bisection), or identify whether or not a duration was the same
      as a previously-presented standard (generalization). They responded faster in the
      bisection task than in the generalization one for long durations. This behavioral
      effect was accompanied by modulation of event-related potentials (ERPs). More
      specifically, between 500 ms and 600 ms after stimulus offset, a late positive
      component (LPC), appearing in the centro-parietal region, showed lower amplitude
      in the bisection task than in the generalization one, for long durations,
      mirroring the behavioral result. Before (200-500 ms) and after (600-800 ms) this
      window, the amplitude of the LPC was globally larger in the generalization
      paradigm, independently of the presented duration. Finally, the LPC amplitude was
      higher for long durations than for shorter ones at the beginning of the component
      (between 200 and 300 ms after stimulus extinction) and was then higher for short
      durations than for longer ones (between 300 and 600 ms after offset), indicating
      that the decision about the former stimuli was made earlier than for the latter
      ones. Taken together, these results indicate that the categorization of durations
      engages fewer cognitive resources than their identification.

PMID- 30189286
TI  - ONEIROS, a new miniature standalone device for recording sleep electrophysiology,
      physiology, temperatures and behavior in the lab and field.
AB  - BACKGROUND: Sleep is an inactive state of reduced environmental awareness shared
      by all animals. When compared to wakefulness, sleep behavior is associated with
      changes in physiology and brain activity. The nature of these changes varies
      considerably across species, and therefore is a rich resource for gaining insight
      into the evolution and functions of sleep. A major obstacle to capitalizing on
      this resource is the lack of a small device capable of recording multiple
      biological parameters for extended periods of time both in the laboratory and the
      field. NEW METHOD: ONEIROS is a new tool designed for conducting sleep research
      on small, freely moving animals. The miniature, standalone system is capable of
      recording up to 26 electrophysiological signals (electroencephalogram,
      electromyogram, electrooculogram, electrocardiogram), metabolic (3 temperature
      channels) and behavior via an accelerometer for several days. In addition, the
      device is equipped with a vibrating motor which can be used to assess arousal
      thresholds and to disrupt sleep. The system is available in telemetric or data
      logger configuration useable in the field. RESULTS: To demonstrate the efficacy
      of this tool, we simultaneously recorded for the first time,
      electroencephalogram, hippocampal local field potential, electromyogram,
      electrooculogram, brain, body and ambient temperature, and 3D accelerometry. We
      also deprived rats of paradoxical sleep by triggering the vibrating motor after
      online recognition of the state. Finally, by successfully recording a pigeon in
      an 8 m3 aviary in a social context with the device in the logger configuration,
      we demonstrate the feasibility of using the device in the field.

PMID- 30189288
TI  - Expectation of exercise in trained athletes results in a reduction of central
      processing to nociceptive stimulation.
AB  - A single endurance exercise session was shown to lead to a reduction of pain
      perception and an elevation of mood. We hypothesized that athletes, who regularly
      practice endurance, might also induce changes in mood and pain processing in
      expectation of an endurance session. We compared the expectation effects of a 2-h
      run on mood and pain processing to a run-free control day (RFC). Fifteen trained
      runners were assessed with repeated painful and nonpainful pinprick stimulation
      in a functional magnetic resonance imaging (fMRI) scanner prior to a 2-h-run and
      at RFC. Pain ratings, pressure pain stimulus-response functions, and euphoria
      ratings were also assessed. There were no mean expectation effects on any of the
      behavioral measures. However, highly trained athletes needed more pressure to
      evoke a pain rating of 46 pre-run vs. RFC but were less euphoric pre-run vs. RFC.
      Furthermore, analysis of brain activities to painful stimuli applied immediately
      before the 2-h-run compared to RFC revealed increased activation in the medial
      prefrontal cortex (mPFC) and reduced activation in posterior insula.
      Additionally, less trained athletes had reduced activation in posterior insula to
      painful stimulation pre-run vs. RFC compared to highly trained athletes. The
      results suggest reduced central pain processing in expectation of an endurance
      run and an association between the amount of the expectation effect and training
      frequency which differs depending on the stimuli applied.

PMID- 30189284
TI  - A Caenorhabditis elegans assay of seizure-like activity optimised for identifying
      antiepileptic drugs and their mechanisms of action.
AB  - BACKGROUND: Epilepsy affects around 1% of people, but existing antiepileptic
      drugs (AEDs) only offer symptomatic relief and are ineffective in approximately
      30% of patients. Hence, new AEDs are sorely needed. However, a major bottleneck
      is the low-throughput nature of early-stage AED screens in conventional rodent
      models. This process could potentially be expedited by using simpler invertebrate
      systems, such as the nematode Caenorhabditis elegans. NEW METHOD: Head-bobbing
      convulsions were previously reported to be inducible by pentylenetetrazol (PTZ)
      in C. elegans with loss-of-function mutations in unc-49, which encodes a GABAA
      receptor. Given that epilepsy-linked mutations in human GABAA receptors are well
      documented, this could represent a clinically-relevant system for early-stage AED
      screens. However, the original agar plate-based assay is unsuited to large-scale
      screening and has not been validated for identifying AEDs. Therefore, we
      established an alternative streamlined, higher-throughput approach whereby
      mutants were treated with PTZ and AEDs via liquid-based incubation. RESULTS:
      Convulsions induced within minutes of PTZ exposure in unc-49 mutants were
      strongly inhibited by the established AED ethosuximide. This protective activity
      was independent of ethosuximide's suggested target, the T-type calcium channel,
      as a null mutation in the worm cca-1 ortholog did not affect ethosuximide's
      anticonvulsant action. COMPARISON WITH EXISTING METHOD: Our streamlined assay is
      AED-validated, feasible for higher throughput compound screens, and can
      facilitate insights into AED mechanisms of action. CONCLUSIONS: Based on an
      epilepsy-associated genetic background, this C. elegans unc-49 model of seizure
      like activity presents an ethical, higher throughput alternative to conventional
      rodent seizure models for initial AED screens.

PMID- 30189289
TI  - Emerging roles of Fgf14 in behavioral control.
AB  - Sexual disturbances, and aggressivity are a major social problem. However, the
      molecular mechanisms involved in the control of these behaviors are largely
      unknown. FGF14, which is an intracellular protein controlling neuronal
      excitability and synaptic transmission, has been implied in neurologic and
      psychiatric disorders. Mice with Fgf14 deletion show blunted responses to drugs
      of abuse. By behavioral tests we show that male Fgf14 knockout mice have a marked
      reduction of several behaviors including aggressivity and sexual behavior. Other
      behaviors driven by spontaneous initiative like burying novel objects and
      spontaneous digging and climbing are also reduced in Fgf14 knockout mice. These
      deficits cannot be attributed to a generalized decrease of activity levels,
      because in the open field test Fgf14 knockout mice have the same spontaneous
      locomotion as wild types and increased rearing. Our results show that Fgf14 is
      important to preserve a set of behaviors and suggest that fine tuning of neuronal
      function by Fgf14 is an important mechanism of control for such behaviors.

PMID- 30189290
TI  - TSPO in diverse CNS pathologies and psychiatric disease: A critical review and a
      way forward.
AB  - The use of Translocator Protein 18 kDa (TSPO) as a clinical neuroimaging
      biomarker of brain injury and neuroinflammation has increased exponentially in
      the last decade. There has been a furious pace in the development of new
      radiotracers for TSPO positron emission tomography (PET) imaging and its use has
      now been extensively described in many neurological and mental disorders. This
      fast pace of research and the ever-increasing number of new laboratories entering
      the field often times lack an appreciation of the historical perspective of the
      field and introduce dogmatic, but unproven facts, related to the underlying
      neurobiology of the TSPO response to brain injury and neuroinflammation.
      Paradoxically, while in neurodegenerative disorders and in all types of CNS
      pathologies brain TSPO levels increase, a new observation in psychiatric
      disorders such as schizophrenia is decreased brain levels of TSPO measured by
      PET. The neurobiological bases for this new finding is currently not known, but
      rigorous experimental design using multiple experimental approaches and careful
      interpretation of results is critically important to provide the methodological
      and/or biological underpinnings to this new observation. This review provides a
      perspective of the early history of validating TSPO as a biomarker of brain
      injury and neuroinflammation and a critical analysis of controversial topics in
      the literature related to the cellular sources of the TSPO response. The latter
      is important in order to provide the correct interpretation of PET studies in
      neurodegenerative and psychiatric disorders. Furthermore, this review proposes
      some yet to be explored explanations to new findings in psychiatric disorders and
      new approaches to quantitatively assess the glial sources of the TSPO response in
      order to move the field forward.

PMID- 30189291
TI  - Genetic variants in major depressive disorder: From pathophysiology to therapy.
AB  - In spite of promising preclinical results there is a decreasing number of new
      registered medications in major depression. The main reason behind this fact is
      the lack of confirmation in clinical studies for the assumed, and in animals
      confirmed, therapeutic results. This suggests low predictive value of animal
      studies for central nervous system disorders. One solution for identifying new
      possible targets is the application of genetics and genomics, which may pinpoint
      new targets based on the effect of genetic variants in humans. The present review
      summarizes such research focusing on depression and its therapy. The
      inconsistency between most genetic studies in depression suggests, first of all,
      a significant role of environmental stress. Furthermore, effect of individual
      genes and polymorphisms is weak, therefore gene x gene interactions or complete
      biochemical pathways should be analyzed. Even genes encoding target proteins of
      currently used antidepressants remain non-significant in genome-wide case control
      investigations suggesting no main effect in depression, but rather an interaction
      with stress. The few significant genes in GWASs are related to neurogenesis,
      neuronal synapse, cell contact and DNA transcription and as being nonspecific for
      depression are difficult to harvest pharmacologically. Most candidate genes in
      replicable gene x environment interactions, on the other hand, are connected to
      the regulation of stress and the HPA axis and thus could serve as drug targets
      for depression subgroups characterized by stress-sensitivity and anxiety while
      other risk polymorphisms such as those related to prominent cognitive symptoms in
      depression may help to identify additional subgroups and their distinct
      treatment. Until these new targets find their way into therapy, the optimization
      of current medications can be approached by pharmacogenomics, where metabolizing
      enzyme polymorphisms remain prominent determinants of therapeutic success.

PMID- 30189292
TI  - Druggable targets in the Rho pathway and their promise for therapeutic control of
      blood pressure.
AB  - The prevalence of high blood pressure (also known as hypertension) has steadily
      increased over the last few decades. Known as a silent killer, hypertension
      increases the risk for cardiovascular disease and can lead to stroke, heart
      attack, kidney failure and associated sequela. While numerous hypertensive
      therapies are currently available, it is estimated that only half of medicated
      patients exhibit blood pressure control. This signifies the need for a better
      understanding of the underlying cause of disease and for more effective
      therapies. While blood pressure homeostasis is very complex and involves the
      integrated control of multiple body systems, smooth muscle contractility and
      arterial resistance are important contributors. Strong evidence from pre-clinical
      animal models and genome-wide association studies indicate that smooth muscle
      contraction and BP homeostasis are governed by the small GTPase RhoA and its
      downstream target, Rho kinase. In this review, we summarize the signaling
      pathways and regulators that impart tight spatial-temporal control of RhoA
      activity in smooth muscle cells and discuss current therapeutic strategies to
      target these RhoA pathway components. We also discuss known allelic variations in
      the RhoA pathway and consider how these polymorphisms may affect genetic risk for
      hypertension and its clinical manifestations.

PMID- 30189293
TI  - Metabolic engineering of Escherichia coli for high-yield uridine production.
AB  - Uridine is a kind of pyrimidine nucleoside that has been widely applied in the
      pharmaceutical industry. Although microbial fermentation is a promising method
      for industrial production of uridine, an efficient microbial cell factory is
      still lacking. In this study, we constructed a metabolically engineered
      Escherichia coli capable of high-yield uridine production. First, we developed a
      CRISPR/Cas9-mediated chromosomal integration strategy to integrate large DNA into
      the E. coli chromosome, and a 9.7 kb DNA fragment including eight genes in the
      pyrimidine operon of Bacillus subtilis F126 was integrated into the yghX locus of
      E. coli W3110. The resultant strain produced 3.3 g/L uridine and 4.5 g/L uracil
      in shake flask culture for 32 h. Subsequently, five genes involved in uridine
      catabolism were knocked out, and the uridine titer increased to 7.8 g/L. As
      carbamyl phosphate, aspartate, and 5'-phosphoribosyl pyrophosphate are important
      precursors for uridine synthesis, we further modified several metabolism-related
      genes and synergistically improved the supply of these precursors, leading to a
      76.9% increase in uridine production. Finally, nupC and nupG encoding nucleoside
      transport proteins were deleted, and the extracellular uridine accumulation
      increased to 14.5 g/L. After 64 h of fed-batch fermentation, the final engineered
      strain UR6 produced 70.3 g/L uridine with a yield and productivity of 0.259 g/g
      glucose and 1.1 g/L/h, respectively. To the best of our knowledge, this is the
      highest uridine titer and productivity ever reported for the fermentative
      production of uridine.

PMID- 30189294
TI  - L-DOPA functionalized, multi-branched gold nanoparticles as brain-targeted nano
      vehicles.
AB  - The blood-brain barrier (BBB) is a protective endothelial barrier lining the
      brain microvasculature which prevents brain delivery of therapies against brain
      diseases. Hence, there is an urgent need to develop vehicles which efficiently
      penetrate the BBB to deliver therapies into the brain. The drug L-DOPA
      efficiently and specifically crosses the BBB via the large neutral amino acid
      transporter (LAT)-1 protein to enter the brain. Thus, we synthesized L-DOPA
      functionalized multi-branched nanoflower-like gold nanoparticles (L-DOPA-AuNFs)
      using a seed-mediated method involving catechols as a direct reducing-cum-capping
      agent, and examined their ability to cross the BBB to act as brain-penetrating
      nanovehicles. We show that L-DOPA-AuNFs efficiently penetrate the BBB compared to
      similarly sized and shaped AuNFs functionalized with a non-targeting ligand.
      Furthermore, we show that L-DOPA-AuNFs are efficiently internalized by brain
      macrophages without inducing inflammation. These results demonstrate the
      application of L-DOPA-AuNFs as a non-inflammatory BBB-penetrating nanovehicle to
      efficiently deliver therapies into the brain.

PMID- 30189296
TI  - How deep do we dig? Formal explanations as placeholders for inherent
      explanations.
AB  - Formal explanations (e.g., "Mittens has whiskers because she's a cat") pose an
      intriguing puzzle in human cognition: they seem like little more than
      tautologies, yet they are surprisingly commonplace and natural-sounding. To
      resolve this puzzle, we hypothesized that formal explanations constitute an
      implicit appeal to a category's inherent features rather than simply to the
      category itself (as their explicit content would suggest); the latter is just a
      placeholder. We conducted a series of eight experiments with 951 participants
      that supported four predictions that followed from this hypothesis: First, formal
      explanations-though natural-sounding-were not particularly satisfying. Second,
      for natural kinds, formal explanations were less satisfying than inherent
      explanations (specifically, ones that appealed to a natural kind's causally
      powerful "essence"). Third, participants viewed essence-related inherent
      explanations as more specific versions of the ideas expressed by formal
      explanations, which were viewed as more general placeholders. Fourth, and
      finally, formal explanations tended to serve as placeholders for explanations
      that appealed to inherent features more so than for other types of explanations,
      such as ones that appealed to external, environmental factors. In addition to
      supporting our novel claim about the meaning of formal explanations, these data
      suggest a new way in which explanations do their psychological work: not via
      their literal content (as assumed by prior work on explanation), but rather via
      the additional inferences they encourage. We end by discussing the potential
      heuristic value of formal explanations for causal learning in childhood.

PMID- 30189295
TI  - Fenfluramine-induced PVAT-dependent contraction depends on norepinephrine and not
      serotonin.
AB  - Perivascular adipose tissue (PVAT) modulates vascular tone and altered PVAT
      function is observed in vascular diseases such as hypertension and
      atherosclerosis. We discovered that the PVAT surrounding rat thoracic aorta (RA)
      and the superior mesenteric artery (SMA) contain significant amounts of 5
      hydroxytryptamine (5-HT). We hypothesized that the 5-HT contained within the PVAT
      is functional and vasoactive. Isolated tissue baths were used for isometric
      contractility studies and high performance liquid chromatography was used to
      quantitatively measure amines in the PVAT and release studies. The 5-HT releaser
      fenfluramine (10 nM-100 MUM) was tested for its ability to contract arteries with
      and without PVAT. Contraction was reported as a percentage of the initial
      contraction to 10 MUM phenylephrine. The RA with PVAT contracted to fenfluramine
      to a greater maximum (98 +/- 10%) than RA without PVAT (24 +/- 4%), while no
      difference in contraction of SMA to maximum fenfluramine with (78 +/- 2%) and
      without (75 +/- 6%) PVAT was observed. Contradicting our hypothesis, the maximum
      contraction of RA with PVAT to fenfluramine was diminished by the alpha-1
      adrenoreceptor antagonist prazosin (100 nM; vehicle: 71 +/- 4%, prazosin: 24 +/-
      2%) and the norepinephrine transporter (NET) inhibitor nisoxetine (1 MUM;
      vehicle: 71 +/- 4%, nisoxetine: 25 +/- 4%) but not the 5-HT2A/2C receptor
      antagonist ketanserin (10 nM) or serotonin specific reuptake inhibitor fluoxetine
      (10 MUM). To test if fenfluramine caused release of 5-HT or NE from PVAT, PVAT
      from RA was incubated with vehicle or fenfluramine (10 MUM-10 mM), and amines
      released into the incubating buffer were quantified. A pronounced concentration
      dependent NE-release (more than 5-HT) was observed. Collectively, this research
      illustrates the pharmacology of fenfluramine to primarily stimulate NE release
      (better than 5-HT) in a NET-dependent manner, leading to vasoconstriction. This
      adds additional support to PVAT as being an important reservoir of amines.

PMID- 30189297
TI  - Any way the wind blows: Children's inferences about force and motion events.
AB  - Goksun, George, Hirsh-Pasek, and Golinkoff (2013) used force dynamics, or the
      semantic categories defined by spatial arrays of forces, to study the development
      of preschoolers' predictions about the outcomes of forces working in concert. The
      current study extends this approach to problems requiring inferences about causal
      factors. In total, 30 5- and 6-year-old children were asked to identify and
      coordinate forces to achieve a result. Problems varied in the number and
      orientation of forces, mirroring spatial arrays characteristic of categories like
      prevent (i.e., opposing forces). Children successfully inferred causes of single-
      and dual-force events, performing best when problems reflected the spatial arrays
      of forces described in language. Results support force dynamics as a valuable
      framework for the development of force and motion representations.

PMID- 30189298
TI  - Minimal Access Surgery for Spinal Metastases: Prospective Evaluation of a
      Treatment Algorithm Using Patient-Reported Outcomes.
AB  - BACKGROUND: Minimal access surgery (MAS) allows for an early return to systemic
      and radiation therapy in patients with cancer, leading to its increasing usage in
      the treatment of spinal metastases. Systematic examination of surgical
      indications resulted in the development of an algorithm for implementation of MAS
      in the treatment of spinal metastases. The objective of the present study was to
      evaluate a spine tumor MAS treatment algorithm using patient-reported outcomes
      for patients with cancer undergoing treatment of spinal metastases. METHODS: We
      performed a prospective cohort study of patients who had undergone spinal
      percutaneous instrumented stabilization with the addition of MAS spinal cord or
      nerve root decompression and/or kyphoplasty when indicated at a tertiary cancer
      center from December 2013 to August 2016. Validated patient-reported outcome
      measures, including the Brief Pain Inventory and the MD Anderson Symptom
      Inventory-spine module, were used. The patient-reported outcome measures were
      collected and compared at baseline, 3 months, and long-term follow-up (range, 4.5
      12 months). RESULTS: A total of 51 patients were included. MAS resulted in a
      statistically significant decrease in the severity of pain and improved activity,
      ability to work, and enjoyment of life (P < 0.001). The improvement was reported
      at the short- and long-term follow-up points. CONCLUSIONS: We present our
      treatment algorithm for MAS implementation in the treatment of thoracolumbar
      spinal metastases. Prospectively collected data have demonstrated that using this
      algorithm, MAS surgery for the treatment of spinal metastases results in
      significant decreases in pain severity and symptom interference with daily
      activities.

PMID- 30189299
TI  - Mechanical Thrombectomy for Acute Anterior Cerebral Artery Occlusion.
AB  - BACKGROUND: We sought to examine the presentation, treatment, and outcomes of
      anterior cerebral artery (ACA) occlusions in patients undergoing mechanical
      thrombectomy (MT). METHODS: Two-hundred ninety-eight consecutive patients with
      large-vessel occlusion treated with MT were analyzed to identify all patients
      with acute ACA occlusion who underwent MT. The primary end point was defined as
      achieving a thrombolysis in cerebral infarction score >=2b. The secondary end
      point included the 90-day modified Rankin Scale (mRS) score and symptomatic
      intracranial hemorrhage. RESULTS: Nine patients with a median National Institutes
      of Health Stroke Scale score of 24 presented with acute ACA occlusion. The median
      time from onset to recanalization was 229 minutes. The ACA occlusion was a
      primary embolic occlusion in 5 patients, secondary to an interventional maneuver
      in 4 patients. Recanalization (thrombolysis in cerebral infarction >=2b) was
      achieved in 9 of 9 patients (100%) without procedural complications. All patients
      had a 90-day mRS score >=3, and 2 patients had an mRS score of 6. Two patients
      developed hemorrhagic infarction, and 1 patient had subarachnoid hemorrhage.
      CONCLUSIONS: Although MT can be considered in patients with ACA occlusions, our
      data suggest that future clinical trials are needed to determine the efficacy of
      MT for ACA occlusions. Unfavorable outcomes in our study were considered to occur
      because of a larger infarct volume due to internal carotid artery, middle
      cerebral artery, and anterior cerebral artery territory infarction. The time from
      onset to recanalization was longer because MT was performed for occlusions of
      multiple arteries.

PMID- 30189300
TI  - Carotid Artery Endarterectomy Versus Carotid Artery Stenting for Patients with
      Contralateral Carotid Occlusion: A Systematic Review and Meta-Analysis.
AB  - BACKGROUND: Results from studies investigating the effect of contralateral
      carotid occlusion (CCO) in patients with carotid artery stenosis undergoing
      carotid artery endarterectomy (CEA) or carotid artery stenting (CAS) are variable
      in the literature. We sought to determine whether CEA or CAS is the optimal
      revascularization approach for patients with CCO. METHODS: This meta-analysis was
      performed according to the Preferred Reporting Items for Systematic Reviews and
      Meta-Analyses guidelines. A random effects model meta-analysis was conducted, and
      the I2 statistic was used to assess for heterogeneity. Subgroup and sensitivity
      analyses were performed as needed. RESULTS: Five retrospective observational
      cohort studies comprising 6346 patients were included. Patients in the CEA group
      had a significantly lower risk of 30-day periprocedural mortality (odds ratio,
      0.46; 95% confidence interval, 0.30-0.71; I2 = 0%). However, no significant
      differences were identified in terms of stroke, myocardial infarction (MI), and
      major adverse cardiovascular events (MACEs) between the 2 groups. Subgroup
      analyses of symptomatic and asymptomatic patients did not yield significant
      differences for stroke, MI, and death. CONCLUSIONS: Patients with CCO can safely
      undergo both CAS and CEA with similar risks of stroke, MI, and MACE. However,
      patients treated with CEA have a lower risk of 30-day periprocedural mortality.
      Future studies can help further clarify the ideal approach for these patients.

PMID- 30189301
TI  - Prognostic Factors and Longitudinal Change in Long-Term Outcome of Frontal Lobe
      Epilepsy Surgery.
AB  - OBJECTIVE: We aimed to investigate the possible predictive factors and
      longitudinal change in long-term surgical outcome after refractory frontal lobe
      epilepsy surgery. METHODS: We retrospectively reviewed 82 patients who underwent
      frontal lobe resection. Invasive monitoring was performed in 43 patients. All
      patients were followed-up for a minimum of 3 years after surgery. Univariate and
      multivariate analyses were used to evaluate the predictors. The Kaplan-Meier
      survival curve showed the estimated probability of complete seizure freedom, and
      a favorable outcome was defined as Engel class I at the last follow-up. RESULTS:
      The estimated probability of complete seizure freedom was 57.3% at 1 year
      postoperatively, 51.2% at 2 years, and 50.0% at 5 years. Factors predictive of
      worse long-term outcome were lack of a lesion in the frontal lobe on magnetic
      resonance imaging, generalized/nonlocalized ictal discharge, use of subdural
      grids, and acute postoperative seizure (APOS). After the surgery, 44 patients
      (53.7%) had seizures at any time during the first 2 years. Five of 44 patients
      had seizure freedom at the last follow-up. After a seizure-free period of at
      least 6 months, seizure recurred in 6 patients by 6 months to 1 year (early
      recurrence) and in 9 patients by 1-3 years (late recurrence). Eight of 43 (18.6%)
      seizure-free patients had discontinued drugs. CONCLUSIONS: The overall seizure
      outcome after surgery changed most during the first 2 years. The presence of
      frontal focal lesions and ictal frontal rhythm predicted favorable outcome.
      However, APOS was predictive of early epilepsy recurrence.

PMID- 30189302
TI  - Risk of Recurrent Chronic Subdural Hematoma Associated with Early Warfarin
      Resumption: A Matched Cohort Study.
AB  - OBJECTIVE: Studies on resuming anticoagulation after burr-hole drainage for
      chronic subdural hematoma (CSDH) are limited. To evaluate the safety for early
      warfarin resumption after burr-hole drainage, we conducted a retrospective
      matched cohort study. METHODS: Between January 2008 and April 2015, 36 patients
      with warfarin-related unilateral CSDH and 151 patients with ordinary unilateral
      CSDH were enrolled in this study. Patients taking warfarin were managed
      homogeneously according to the study protocol, and the usual dosage of warfarin
      was resumed within 2 or 3 days of burr-hole drainage to reach a target
      international normalized ratio (INR) of 2.1. The primary outcome, defined as
      recurrent CSDH requiring repeated burr-hole drainage within 3 months of the
      initial surgery, was compared between the two groups. RESULTS: The primary
      outcome was observed in 4 (11%) of the 36 patients taking warfarin and in 18
      (12%) of the 151 ordinary patients. After propensity score matching, the primary
      outcome was observed in 3 of 33 patients (9%) in the matched warfarin cohort and
      11 of 74 patients (15%) in the matched ordinary cohort. When the results were
      analyzed using the generalized estimating equation, no significant difference was
      observed in the rate of recurrent CSDH between the 2 groups (P = 0.411). In
      addition, we found that recurrent CSDH was not related to postoperative
      international normalized ratio levels (P = 0.332). CONCLUSIONS: There was no
      definitive association between postoperative early warfarin resumption and the
      recurrence rate of CSDH. Patients with warfarin-related CSDH and a strong
      indication for anticoagulation can be managed by resuming warfarin within 3 days
      of burr-hole drainage.

PMID- 30189304
TI  - Comparison of Clinical and Radiologic Outcomes of Diverse Endovascular Treatments
      in Vertebral Artery Dissecting Aneurysm Involving the Origin of PICA.
AB  - BACKGROUND: The aim of this study was to determine clinical and radiologic
      outcomes of vertebral artery dissecting aneurysm (VADA) involving posterior
      inferior cerebellar artery (PICA) according to different types of endovascular
      treatment. METHODS: A total of 18 VADAs (six ruptured and 12 unruptured)
      involving PICA from January 2009 to December 2016 were included in this study.
      Multiple stenting, stent assisted coil embolization, VA trapping with PICA-VA
      stenting, and pipeline embolization were performed as treatment. Retrospective
      chart review and radiologic review were done to obtain clinical and radiologic
      information. RESULTS: Of 18 patients, six were diagnosed with SAH and two were
      diagnosed with infarction initially. Multiple stenting was performed in four
      patients, including one (25%) who had cerebellar infarction and one (25%) who had
      recurrence. Stent assisted coil embolization was performed in eight patients,
      including one (12.5%) who had postoperative cerebellar infarction and two (25%)
      who had recurrence. VA trapping with PICA-VA stent was performed in four
      patients, including one (25%) who had postoperative cerebellar infarction.
      However, there was no recurrence (0%). Pipeline embolization was performed for
      two patients, including one (50%) who had recurrence. There was no postoperative
      infarction (0%). No subarachnoid hemorrhage occurred during the follow-up period.
      mRS deterioration was only found in the SAC group (1/8, 12.5 %). CONCLUSIONS:
      Vertebral artery trapping with PICA-VA stenting showed the lowest rate of
      aneurysm recurrence with a high rate of minor infarction and favorable neurologic
      outcome. Stent assisted coil embolization showed a high recurrence rate with
      possibility of fatal disabling infarction.

PMID- 30189303
TI  - Dermoid and Epidermoid Cysts of Scalp: Case Series of 234 Consecutive Patients.
AB  - BACKGROUND: Dermoid and epidermoid cysts are among the most frequent lesions of
      the scalp in the pediatric population. Optimal management of a suspected dermoid
      or epidermoid cyst in children is debated: Some authors advocate conservative
      management on the basis of the benign histology of these entities, while others
      prefer surgical excision. OBJECTIVE: Our objective is to demonstrate that
      excision of dermoid and epidermoid cysts is a safe procedure and that early
      surgery is effective in preventing potential complications related to cyst
      growth. METHODS: We retrospectively collected data on patients who underwent
      surgery for excision of proven dermoid or epidermoid cysts between January 2006
      and October 2017. RESULTS: In 234 patients, 237 cysts were excised. Mean age at
      presentation was 26.99 +/- 32.7 months; 48.7% of patients were operated on
      between 1 and 3 years of age, and 32.9% were younger than 1 year of age. Cysts
      were more frequently located in the frontal bone than in occipital and
      supraorbital regions. In 36.28% of cases there was no significant cranial
      impingement, while 21.94% of the cysts eroded through a partial thickness of the
      cranium, 12.23% were in the full thickness of the skull, and 0.84% had epidural
      extension. We identified 22 intradiploic cysts. Statistical analysis demonstrated
      significant association between frontal and pterional localization and bone
      erosion. Neither major complications nor cyst recurrence were observed.
      CONCLUSIONS: Excision of dermoid and epidermoid cysts is a safe procedure for
      neurosurgeons dealing with this disease, even in young patients. Early resection
      is recommended due to the potential adverse effects that may occur if these cysts
      are left untreated.

PMID- 30189305
TI  - Pituitary Apoplexy in Long-Term Cabergoline User During Thrombocytopenia Due to
      Chemotherapy for Chronic Myelocytic Leukemia.
AB  - BACKGROUND: Pituitary apoplexy (PA) is a life-threatening syndrome. The usage of
      a dopamine agonist, such as bromocriptine or cabergoline, is considered a
      predisposing factor for PA, which commonly occurs 1.5 years within commencement.
      CASE DESCRIPTION: A 64-year-old female with a >15-year history of cabergoline
      therapy for pituitary prolactinoma was referred to our department of neurosurgery
      after complaining of headache, blurred vision, diplopia, and ptosis for 3 days
      during hospital admission for chemotherapy of chronic myelocytic leukemia.
      Computed tomography and magnetic resonance imaging revealed findings indicative
      of PA. As the patient was experiencing thrombocytopenia related to chemotherapy,
      blood transfusion was preceded, and after a platelet count of 15.0 * 104/MUL was
      confirmed, transnasal neuroendoscopic surgery was performed 5 days from the onset
      of symptoms. The majority of the prolactinoma was removed, and the prolactinoma
      in the cavernous sinus was intentionally left. The postoperative course was
      generally good. The ptosis and diplopia improved, and the blurred vision
      resolved. CONCLUSIONS: PA related to dopamine agonist therapy can occur in cases
      of elevated bleeding tendency, even in long-term users, suggesting that attention
      should be paid in the administration of a dopamine agonist in the patient
      experiencing thrombocytopenia. Surgical intervention should be performed after
      the preoperative platelet number and adequate response to transfusion are
      confirmed, and the aggressive removal of prolactinoma in the cavernous sinus
      should be avoided to reduce the risk of hemorrhagic complications.

PMID- 30189306
TI  - Defining Hypotension in Patients with Severe Traumatic Brain Injury.
AB  - BACKGROUND: Hypotension, a risk factor for increased mortality following
      traumatic brain injury (TBI), is traditionally defined as systolic blood pressure
      (SBP) <90 mm Hg. We aimed to redefine hypotension and determine its optimal
      threshold in patients with TBI. METHODS: We identified patients with severe TBI
      (Glasgow Coma Scale score <=8 on admission) between 2004 and 2015 using data from
      the Japan Trauma Data Bank. Our endpoint was in-hospital mortality. Mixed effects
      logistic regression models were used to investigate the association between SBP
      on admission and in-hospital mortality, with hospitals considered as a random
      effects variable. We also conducted analyses stratified by age (<=60 years and
      >60 years) to determine age-specific optimal levels of SBP. RESULTS: A total of
      12,537 patients (5665 patients <=60 years old and 6872 patients >60 years old)
      were eligible for the analyses. Overall, SBP of 110 mm Hg was the optimal
      threshold for hypotension, and adjusted odds ratio and C-statistic for mortality
      at SBP <110 mm Hg on admission were 1.58 (95% confidence interval, 1.42-1.76, P <
      0.001) and 0.78 (95% confidence interval, 0.77-0.79), respectively. Stratified
      analyses showed that optimal thresholds for hypotension in patients <=60 years
      old and >60 years old were 100 mm Hg and 120 mm Hg. CONCLUSIONS: The threshold
      for hypotension in patients with severe TBI should be redefined and modified by
      age, and patients <=60 years old should be considered hypotensive at SBP <100 mm
      Hg, whereas in older patients, SBP <120 mm Hg should be diagnosed as hypotension.

PMID- 30189307
TI  - Transfacet and Transpedicular Posterior Approaches to Thoracic Disc Herniations:
      Consecutive Case Series of 24 Patients.
AB  - OBJECTIVE: Various approaches are advocated for symptomatic thoracic disc
      herniation (TDH). The aim of this series is to demonstrate the feasibility,
      safety, and results of posterior transfacet or transpedicular approaches for
      excision of all types of extradural TDH. We report a consecutive series of
      patients undergoing posterior approach surgery for TDH. METHODS: Twenty-four
      patients (17 women, 7 men) underwent surgery at 25 disc levels. Mean age was 56.3
      years (range, 23-79 years). A posterior transfacet or transpedicular approach was
      used. Patients presented with myelopathy (n = 21, 88%), radiculopathy (n = 8,
      33%), sphincter dysfunction (n = 16, 67%), and axial back pain (n = 10, 43%).
      Preoperative imaging revealed 7 (30%) central, 14 (61%) calcified, and 10 (43%)
      large disc herniations. The mean follow-up period was 6.0 months (range, 2-36
      months). RESULTS: Eighteen patients underwent unilateral approach surgery (5
      transfacet and 13 transfacet plus transpedicular), and 7 patients required
      bilateral approach laminectomy for unilateral (n = 4) or bilateral (n = 3)
      discectomy. One patient required unplanned reoperation for resection of residual
      disc. Average operative time was 95 minutes (range, 40-175 minutes). Mean
      hospital stay was 4.9 days (range, 2-35 days). There were no major complications.
      Postoperative Frankel scores were maintained or improved in all patients at last
      review. CONCLUSIONS: TDH including large central calcified discs can be safely
      removed through posterior transfacet or transpedicular approaches with reduced
      morbidity in comparison with more invasive anterior approaches. Careful
      microsurgical technique and use of specialized instruments are important for
      successful excision of TDH from a posterior approach.

PMID- 30189308
TI  - Preoperative Imaging and Microscopic Navigation During Surgery Can Avoid
      Unnecessarily Opening the Mastoid Air Cells Through Craniotomy Using the
      Retrosigmoid Approach.
AB  - OBJECTIVE: To analyze treatment of microvascular decompression using the
      retrosigmoid approach (RA) in primary trigeminal neuralgia and hemifacial spasm
      using preoperative images combined with intraoperative microscopic navigation to
      avoid unnecessarily opening the mastoid air cells (MACs). METHODS: Ten patients
      with primary trigeminal neuralgia and 20 patients with hemifacial spasm (test
      group) were treated using RA for microvascular decompression. Preoperative head
      magnetic resonance angiography and temporal bone computed tomography were
      performed and the images registered using SPM12 and fused with MRIcron to
      determine the relationship between MACs and sigmoid sinuses. An O-arm was used
      for navigation, and the transverse sigmoid sinus was projected under a microscope
      to guide RA. A control group comprised 139 patients who had the same surgical
      procedure as the test group but without image processing or intraoperative
      navigation. RESULTS: The relationship between MACs and the ipsilateral sigmoid
      sinus was classified as follows: I, MACs did not exceed the lateral edge of the
      ipsilateral sigmoid sinus (10/60); II, MACs exceeded the ipsilateral lateral edge
      of the sigmoid sinus but did not exceed the medial edge (42/60); and III, MACs
      exceeded the medial edge of the ipsilateral sigmoid sinus (8/60). Test and
      control groups showed significant differences in the incidences of opening MACs
      (P = 0.003). There was no cerebrospinal fluid leakage or scalp and intracranial
      infection at follow-up. CONCLUSIONS: Image processing and intraoperative
      microscopic navigation can avoid unnecessarily opening MACs and might reduce
      postoperative cerebrospinal leakage and scalp infection after RA craniotomy.

PMID- 30189309
TI  - Muslin Granuloma Mimicking Parenchymal Hematoma in Patient with Seizures 30 Years
      After Aneurysm Wrapping.
AB  - Muslin foreign body granulomas are a known complication of muslin aneurysm
      wrapping and have been associated with vision loss from optochiasmatic
      arachnoiditis. Muslin granulomas have also been confused with abscesses due to
      surrounding inflammatory changes. In this clinical image, we present a unique
      case of a muslin granuloma mimicking an intraparenchymal hematoma.

PMID- 30189310
TI  - Perioperative Risk Factors for Thirty-Day Morbidity and Mortality in the
      Resection of Extradural Thoracic Spine Tumors.
AB  - OBJECTIVE: Resection of epidural thoracic spine tumors is uniquely challenging
      owing to the dangers posed by the surrounding anatomy and the unforgiving nature
      of the thoracic spinal cord. We assessed the preoperative and postoperative risk
      factors for 30-day morbidity and mortality in patients undergoing resection of
      these tumors. METHODS: Adults who underwent laminectomy for excision of thoracic
      spine tumors from 2011 to 2014 were included. The demographic data and medical
      comorbidities and major morbidities and mortalities within 30 postoperative days
      were collected and assessed using multivariate binary logistic analysis. RESULTS:
      The database search yielded 616 patients, of whom 232 (37.7%) were female.
      Overall, complications within 30 days of surgery occurred in 322 patients
      (52.3%). Of the 616 patients, 64 (10.4%) died within 30 days of surgery. Smoking
      history was associated with significantly greater 30-day morbidity (P = 0.019),
      as was preoperative anemia for females (P = 0.003) and preoperative
      hypoalbuminemia (P < 0.0001), with the need for preoperative blood transfusion
      also leading to greater morbidity (P = 0.001). The presence of preoperative
      dyspnea and congestive heart failure increased the risk of complications (P =
      0.001). Preoperative hypoalbuminemia (odds ratio [OR], 3.6; 95% confidence
      interval [CI], 1.8-7.0), dependent functional status (OR, 3.6; 95% CI, 1.7-7.6),
      and bleeding disorder (OR, 7.1; 95% CI, 2.5-20.1) were significantly associated
      with 30-day mortality. Deep vein thrombosis/pulmonary embolism, nonthrombotic
      pulmonary complications, and blood transfusions were common post- and
      perioperative complications. CONCLUSIONS: Excision of epidural thoracic spinal
      tumors carries a high complication rate. The present series has revealed distinct
      preoperative and postoperative factors that contribute to 30-day morbidity and
      mortality for tumors in this region, many of which are amenable to careful
      preoperative management.

PMID- 30189311
TI  - The Clival Line as an Important Arachnoid Landmark During Endoscopic Third
      Ventriculostomy: An Anatomic Study.
AB  - OBJECTIVE: Endoscopic third ventriculostomy (ETV) is a well-accepted treatment
      option instead of ventriculoperitoneal shunt placement in cases of obstructive
      hydrocephalus. A sufficient flow from the ventricles to the basal cisterns
      requires perforation of the arachnoid membranes in the retroclival region. This
      point is critical to achieve an optimal outcome. The complex arachnoid relations
      were investigated in the retroclival region from the viewpoint of ETV, and
      anatomic landmarks were defined for subarachnoid dissections. METHODS: Sixty
      fresh human cadaveric specimens were dissected under macroscopic, microscopic,
      and endoscopic control. The recordings of 100 operated cases of ETVs were
      analyzed to ascertain the clinical-anatomic relevance. RESULTS: The Liliequist
      membrane complex and the anterior pontine membranes are located just above and
      parallel to both sides of the basilar artery. The basal attachment of these
      membranes forms an inverted U-shaped, white-grey thickening on the outer
      arachnoid. We refer to this structure as the clival line. During ETV, if
      arachnoid dissections were performed ventrally to the clival line, the outer
      arachnoid was opened; this resulted in a limited flow to the subarachnoid spaces
      (ventriculo-subdural). If the perforation on the arachnoid membranes was dorsal
      to the clival line, the prepontine cistern could be directly reached through the
      Liliequist membrane complex. CONCLUSIONS: Sufficient arachnoid dissection is
      essential for a successful ETV. The clival line is an important landmark that
      helps to perform the subarachnoid dissections correctly and achieve an
      undisrupted cerebral spinal fluid flow between the ventricles and the basal
      cisterns.

PMID- 30189312
TI  - The Unique Features and Outcomes of Microsurgically Resected Cerebellar
      Arteriovenous Malformations.
AB  - BACKGROUND: Cerebellar arteriovenous malformations (CAVMs) are challenging to
      treat given their close proximity to the brain stem, greater propensity for
      rupture, and greater rates of morbidity and mortality than other brain
      arteriovenous malformations. The present investigation sought to describe and
      characterize the features of these rare and unique lesions. METHODS: A
      retrospective review of CAVM cases treated at 2 tertiary medical centers was
      performed. Patients surgically treated at institution 1 from September 1999 to
      February 2013 and institution 2 from October 2008 to October 2015 were included.
      RESULTS: A total of 120 patients had been treated. Of the 120 patients, 85
      (70.8%) had initially presented with hemorrhage, 45 (37.5%) of whom experienced
      hemorrhage requiring emergent surgery. A favorable neurological outcome was
      observed in 76 patients (63.3%; modified Rankin Scale score <3). The
      perioperative mortality was 2.5% (n = 3). The long-term mortality rate was 7.5%
      (n = 9). The mean follow-up time was 1.82 years. On average, the patients with
      large CAVMs (>=3 cm; P <= 0.001), who had received embolization before surgery (P
      = 0.04), did not have an associated aneurysm (P <= 0.001), or had a residual CAVM
      after surgery (P = 0.008) were significantly younger. Female patients had fewer
      CAVMs with deep venous drainage (54.3% vs. 72.3%; P = 0.049), experienced
      decreased mortality (1.4% vs. 16.7%; P = 0.003), and were less likely to have
      worse neurological status after treatment (P = 0.003). CONCLUSIONS: CAVMs are
      rare lesions that exhibit unique disease characteristics. Although most patients
      will experience a favorable outcome, CAVMs frequently present with hemorrhage,
      result in high rates of morbidity and mortality, and characteristically differ
      depending on patient age and gender.

PMID- 30189313
TI  - Outcomes of Operative and Nonoperative Treatment in Patients with Adult Spinal
      Deformity with a Minimum 2-Year Follow-Up: A Meta-Analysis.
AB  - BACKGROUND: More recent studies have focused on clinical outcomes of operative
      versus nonoperative treatment in patients with adult spinal deformity (ASD).
      However, scientific support for ASD surgery is weak. We compared outcomes of
      operative and nonoperative treatment of ASD with minimum 2-year follow-up in a
      meta-analysis. METHOD: MEDLINE and EMBASE databases, from the earliest available
      date of indexing through May 10, 2018, were searched for studies evaluating
      outcomes of operative and nonoperative treatment of ASD. Two authors performed
      data extraction independently. Any discrepancies were resolved by consensus.
      RESULTS: Four comparative studies were identified. Postoperative back pain
      numeric rating scale and leg pain numeric rating scale scores were significantly
      lower with operative treatment compared with nonoperative treatment (P < 0.00001,
      weighted mean difference [WMD] = -2.76 [-3.45, -2.07] vs. P < 0.0001, WMD = -2.31
      [-3.33, -1.28]). Postoperative Oswestry Disability Index and Scoliosis Research
      Society-22 questionnaire scores were significantly better with operative
      treatment compared with nonoperative treatment (P < 0.00001, WMD = -10.96 [
      13.56, -8.36] vs. P < 0.00001, WMD = 0.68 [0.48, 0.87]). The complication rate of
      operative treatment was 17%-71.5%. CONCLUSIONS: Our meta-analysis showed that
      operative treatment has been demonstrated to significantly reduce disability and
      pain and to improve clinical outcomes compared with nonoperative treatment.
      Further large, multicenter, well-designed studies are necessary to substantiate
      our results.

PMID- 30189314
TI  - Computer-Assisted Analysis of Intracerebral Hemorrhage Shape and Density.
AB  - BACKGROUND: Shape and density of intracerebral hemorrhage (ICH) are associated
      with a higher risk of poor treatment outcome. However, methods of assessment for
      the features are still inconclusive. Therefore, we decided to measure ICH shape
      irregularity using shape factors to achieve objective results. METHODS: We
      retrospectively analyzed 48 patients with spontaneous ICH confirmed by head
      computed tomography (CT) scan. We obtained detailed medical history and blood
      test results from medical records. On admission patients were assessed using
      Glasgow Coma Scale score, and on discharge patients were assessed using Glasgow
      Outcome Scale (GOS) score. GOS score of less than 3 was defined as poor outcome.
      For each slice of CT scan with visible ICH, we extracted its contour and
      calculated the fractal dimension (FD), compactness (C), and Fourier factor (FF).
      We also calculated the circle factor (CF), which was defined as the contour
      perimeter/perimeter of the biggest circle that can be inscribed into the contour,
      and density heterogeneity, defined as the variance of pixel density. RESULTS: A
      total of 28 patients (58.33%) had poor treatment outcome. Those patients had
      significantly higher C (0.71 +/- 0.09 vs. 0.59 +/- 0.09; P < 0.01), FD (1.42 +/-
      0.12 vs. 1.27 +/- 0.09; P < 0.01), and CF (3.59 +/- 0.92 vs. 2.63 +/- 0.63; P <
      0.01). In multivariate logistic regression analysis, FD (odds ratio, 4.176; 95%
      confidence interval, 1.551-15.577; P = 0.012) remained independently associated
      with higher risk of poor treatment outcome. CONCLUSIONS: Each of the shape
      descriptors, except FF, was associated with treatment outcome after ICH. FD can
      be used as an independent predictor of outcome.

PMID- 30189315
TI  - Hybrid Operating Room Settings for Treatment of Complex Dural Arteriovenous
      Fistulas.
AB  - OBJECTIVE: Dural arteriovenous fistulas (dAVFs) are abnormal direct shunts
      between the occipital or meningeal artery and a meningeal vein or dural venous
      sinus. Treatment strategies include endovascular, microsurgical, stereotactic
      radiosurgical, or combined interventions. With few previous reports focused on
      dAVF treatment in a hybrid operating room (hOR), the authors reviewed their 6
      year experience in this unique setting for these complex fistulas. METHODS:
      Patients with complex cerebral dAVFs underwent endovascular and microsurgical
      treatment in the hOR. In this retrospective review, 8 consecutive patients with
      cerebral dAVFs (Borden type 2 or higher) underwent endovascular and microsurgical
      treatment. Demographic characteristics, symptoms related to the dAVF,
      preoperative angiographic features, preinterventional therapies, intraoperative
      digital subtraction angiography (iDSA), and postoperative clinical and radiologic
      findings were reviewed. RESULTS: Of these 8 patients, 5 patients underwent
      multiple embolizations (up to 3) and hybrid procedures, with no procedure-related
      complications. After microsurgical resection, iDSA revealed remnants of the
      fistula, which was then immediately re-resected, in 2 patients. At closing of the
      hybrid procedure, iDSA revealed no fistula remnants in 7 patients (88%). At mean
      follow-up examination (58 months), 5 patients (62%) had cure of the dAVF,
      confirmed by noninvasive angiography. Two patients (25%) experienced a recurrence
      of the dAVF within 5 months. CONCLUSIONS: Our hybrid techniques achieved high
      rates of dAVF obliteration, with all 8 patients achieving good or excellent
      outcomes and symptom relief. Angiographic follow-up within 6 months after the
      hybrid procedure is recommended for all patients even when intraoperative
      findings do not show remnants.

PMID- 30189316
TI  - Protective effects of Manuka honey on LPS-treated RAW 264.7 macrophages. Part 1:
      Enhancement of cellular viability, regulation of cellular apoptosis and
      improvement of mitochondrial functionality.
AB  - Manuka honey (MH) is a monofloral honey from Australia and New Zealand, well
      known for its healthy properties, such as antioxidant, antimicrobial and wound
      healing capacities. The aim of this work was to assess the phenolic composition
      and the total antioxidant capacity (TAC) of MH, as well as its effects on
      cellular viability, proliferation, apoptosis and metabolism in lipopolysaccharide
      (LPS)-treated RAW 264.7 macrophages, highlighting the molecular mechanisms
      involved. Up to 18 compounds were identified in MH, with gallic acid and
      quercetin as the major ones; MH showed also remarkable TAC. In addition, MH was
      able to enhance cellular viability, decrease apoptosis, promote wound healing and
      attenuate inflammation in a dose-dependent manner, by reducing the expression of
      caspase 3, p-p38 and p-Erk1/2 proteins, in macrophages stressed with LPS. In
      addition, it improved mitochondrial respiration and glycolytic activities,
      stimulating the expression of p-AMPK, SIRT1 and PGC1alpha, counteracting in this
      way the deleterious effects of LPS treatment. In conclusion, one of the possible
      mechanisms by which MH exerts its beneficial effects could be to its capacity to
      improve cellular viability, promote proliferation and enhance energetic
      metabolism, by modulating the expression of several proteins involved in
      apoptosis, inflammation, metabolism and mitochondrial biogenesis.

PMID- 30189317
TI  - RIFM fragrance ingredient safety assessment, trans-2-hexenoic acid, CAS Registry
      Number 13419-69-7.

PMID- 30189319
TI  - Hidden diversity within the depauperate genera of the snake tribe Lampropeltini
      (Serpentes, Colubridae).
AB  - Accurate representation of lineage diversity through complete taxon sampling is
      crucial to understanding the evolution of biodiversity, particularly when using
      molecular phylogenetics to estimate evolutionary relationships. In this interest,
      taxonomic diversity is often used as a proxy for lineage diversity even though
      the two concepts are not synonymous. We explore this within the snake tribe
      Lampropeltini which includes some of the most conspicuous and heavily studied
      snakes in North America. Both the taxonomy and hypothesized relationships within
      this tribe have been in flux. The number of species has increased from 23 to 51
      over the last thirty years, predominately within three of the nine genera
      (Lampropeltis, Pantherophis, Pituophis). The remaining six depauperate genera
      (Arizona, Bogertophis, Cemophora, Pseudelaphe, Rhinocheilus, and Senticolis) have
      been poorly represented in phylogenetic studies. To estimate evolutionary
      relationships and determine if the dichotomy in depauperate and speciose genera
      within Lampropeltini is a function of taxon sampling or truly represents the
      lineage diversity, we estimated the phylogeny of this group using nuclear and
      mitochondrial loci in a concatenated and coalescent framework with the largest
      sampling of the six depauperate genera to date. In addition, we estimated the
      divergence dates among the genera to assess whether the instability of
      Lampropeltini phylogenetic relationships is due to an adaptive radiation. While
      some nodes still remain unresolved, the generic-level relationships we recovered
      agree with those of a recent next-generation study that used a much larger set of
      loci for fewer individuals. We also tested two putative species, Arizona pacata
      and Pseudelaphe phaescens, for the first time phylogenetically and find evidence
      that they are distinct lineages. Overall, we find that the taxonomic and genetic
      diversity are not correlated in Lampropeltini and that representing putative
      diversity in phylogenies will lead to a better estimate of evolutionary
      histories, especially in groups with complex radiations.

PMID- 30189318
TI  - RIFM fragrance ingredient safety assessment, 2,4,4,7-tetramethylnona-6,8-dien-3
      one, CAS Registry Number 81782-89-0.

PMID- 30189320
TI  - Quorum sensing molecules regulate epithelial cytokine response and biofilm
      related virulence of three Prevotella species.
AB  - Quorum sensing (QS) signaling regulates the motility, adhesion, and biofilm
      formation of bacteria, and at the same time activates immune response in
      eukaryotic organisms. We recently demonstrated that the QS molecule, dihydroxy-2,
      3-pentanedione (DPD), and its analogs significantly inhibit estradiol-regulated
      virulence of Prevotella aurantiaca, one of the four species in the Prevotella
      intermedia group. Here, we examined the combined effects of estradiol and QS
      signaling on 1) cytokine response of human gingival keratinocytes (HMK) against
      whole cell extract (WCE) of P. intermedia, Prevotella nigrescens, and Prevotella
      pallens, and 2) biofilm formation of these three Prevotella species. All
      experiments were performed in the presence or absence of estradiol, and with
      different QS molecules: DPD and its analogs (ethyl-DPD, butyl-DPD, and isobutyl
      DPD). Concentrations of interleukin (IL)-1beta, -6, and -8 were determined by the
      Luminex multiplex immunoassay, biofilm mass was quantitatively evaluated by
      measuring protein concentration via the Bradford method, and the microtopography
      of biofilms was assessed by scanning electron microscopy (SEM) imaging.
      Concentrations of IL-6 and IL-8 were elevated when HMK cells were incubated with
      estradiol and WCE of P. intermedia and P. nigrescens, but decreased when
      incubated with estradiol and WCE of P. pallens. Butyl-DPD neutralized the
      estradiol- and WCE-induced regulation of HMK interleukin expression and, at the
      same time, inhibited the biofilm formation of P. intermedia and P. nigrescens.
      SEM micrographs revealed a decrease in biofilm mass after application of butyl
      DPD, which was most detectable among the P. intermedia ATCC 25611 and P.
      nigrescens ATCC 33563 and AHN 8293 strains. In conclusion, butyl-DPD analog is
      able to neutralize the WCE-induced epithelial cytokine response and, at the same
      time, to inhibit the biofilm formation of P. intermedia and P. nigrescens.

PMID- 30189321
TI  - New software tools in EMAN2 inspired by EMDatabank map challenge.
AB  - EMAN2 is an extensible software suite with complete workflows for performing high
      resolution single particle analysis, 2-D and 3-D heterogeneity analysis, and
      subtomogram averaging, among other tasks. Participation in the recent CryoEM Map
      Challenge sponsored by the EMDatabank led to a number of significant improvements
      to the single particle analysis process in EMAN2. A new convolutional neural
      network particle picker was developed, which dramatically improves particle
      picking accuracy for difficult data sets. A new particle quality metric capable
      of accurately identifying "bad" particles with a high degree of accuracy, no
      human input, and a negligible amount of additional computation, has been
      introduced, and this now serves as a replacement for earlier human-biased
      methods. The way 3-D single particle reconstructions are filtered has been
      altered to be more comparable to the filter applied in several other popular
      software packages, dramatically improving the appearance of sidechains in high
      resolution structures. Finally, an option has been added to perform local
      resolution-based iterative filtration, resulting in local resolution improvements
      in many maps.

PMID- 30189323
TI  - RNA-seq coupled to proteomic analysis reveals high sperm proteome variation
      between two closely related marine mussel species.
AB  - : Speciation mechanisms in marine organisms have attracted great interest because
      of the apparent lack of substantial barriers to genetic exchange in marine
      ecosystems. Marine mussels of the Mytilus edulis species complex provide a good
      model to study mechanisms underlying species formation. They hybridise
      extensively at many localities and both pre- and postzygotic isolating mechanisms
      may be operating. Mussels have external fertilisation and sperm cells should show
      specific adaptations for survival and successful fertilisation. Sperm thus
      represent key targets in investigations of the molecular mechanisms underlying
      reproductive isolation. We undertook a deep transcriptome sequencing (RNA-seq) of
      mature male gonads and a 2DE/MS-based proteome analysis of sperm from Mytilus
      edulis and M. galloprovincialis raised in a common environment. We provide
      evidence of extensive expression differences between the two mussel species, and
      general agreement between the transcriptomic and proteomic results in the
      direction of expression differences between species. Differential expression is
      marked for mitochondrial genes and for those involved in spermatogenesis, sperm
      motility, sperm-egg interactions, the acrosome reaction, sperm capacitation, ATP
      reserves and ROS production. Proteins and their corresponding genes might thus be
      good targets in further genomic analysis of reproductive barriers between these
      closely related species. SIGNIFICANCE: Model systems for the study of
      fertilization include marine invertebrates with external fertilisation, such as
      abalones, sea urchins and mussels, because of the ease with which large
      quantities of gametes released into seawater can be collected after induced
      spawning. Unlike abalones and sea urchins, hybridisation has been reported
      between mussels of different Mytilus spp., which thus makes them very appealing
      for the study of reproductive isolation at both pre- and postzygotic levels.
      There is a lack of empirical proteomic studies on sperm samples comparing
      different Mytilus species, which could help to advance this study. A comparative
      analysis of sperm proteomes across different taxa may provide important insights
      into the fundamental molecular processes and mechanisms involved in reproductive
      isolation. It might also contribute to a better understanding of sperm function
      and of the adaptive evolution of sperm proteins in different taxa. There is now
      growing evidence from genomics studies that multiple protein complexes and many
      individual proteins might have important functions in sperm biology and the
      fertilisation process. From an applied perspective, the identification of sperm
      specific proteins could also contribute to the improved understanding of
      fertility problems and as targets for fertility control.

PMID- 30189322
TI  - Investigation of the dynamical expression of Nostoc flagelliforme proteome in
      response to rehydration.
AB  - : To adapt to xeric environments, microorganisms have evolved with the capability
      of the superior desiccation tolerance and rapid resuscitation after rehydration.
      Nostoc flagelliforme, a representative terrestrial cyanobacterium that is
      distributed in west and west-northern parts of China, serves as an ideal model
      for gaining insight in the physiological recovery mechanism. In this study, LC
      MS/MS combined with isobaric chemical labeling technique (iTRAQ) was used to
      quantify dynamic changes of proteins in N. flagelliforme during the rehydration
      processes. Approximately 113 proteins were identified to be differentially
      expressed, with function mainly related to photosynthesis, defense response,
      biosynthesis, antioxidant system, and energy and carbohydrate metabolism. Among
      them, protective proteins including high light inducible proteins and
      antioxidants showed a down regulation trend during the rehydration process, while
      proteins involved in photosynthesis, biosynthesis and signaling pathways and
      regulation of gene expression tend to be up-regulated. These results might shed
      light on molecular mechanism for the N.flagelliforme response to hydration.
      SIGNIFICANCE: In this work, iTRAQ-based proteome expression profiling provides a
      holistic proteomic insight for N. flagelliforme in response to rehydration
      processes. Proteins involved in defense system could help to limit the damage to
      a repairable level and maintain cellular physiological integrity in the dried
      state. In addition, results in this work suggest that changes in expression of
      light-harvesting complexes phycobilisome is closely related to the switch of
      photosynthesis apparatus, while only a few proteins in PSI and PSII present
      significant expression change, which may indicate the integrity of PSI and PSII
      photosynthetic system.

PMID- 30189324
TI  - Epidemiology and survival of blastic plasmacytoid dendritic cell neoplasm.

PMID- 30189325
TI  - Association between resting-state brain functional connectivity and cortisol
      levels in unmedicated major depressive disorder.
AB  - Disturbed hypothalamus-pituitary-adrenal axis function, which leads to excessive
      and prolonged hypercortisolemia, is a core feature of major depressive disorder
      (MDD). However, the relationships between depression, brain structure and
      function, and cortisol levels are unclear. The current study examined the whole
      brain functional connectivity pattern of patients with MDD and evaluated the
      association between functional connectivity and serum cortisol levels in MDD. A
      total of 93 unmedicated patients with MDD and 139 healthy control subjects
      underwent resting-state functional magnetic resonance imaging. Voxel-wise whole
      brain connectivity was analyzed by using a graph theory approach: functional
      connectivity strength (FCS). A seed-based resting-state functional connectivity
      analysis was further performed to investigate abnormal functional connectivity
      patterns of those regions with changed FCS. Morning blood samples were drawn for
      cortisol measurements in some subjects (including 53 MDD patients and 30
      controls). The MDD patients had a significantly lower FCS in the left posterior
      lobes of the cerebellum (mainly lobule Crus II) (p < 0.05, TFCE corrected). The
      seed-based functional connectivity analysis revealed decreased functional
      connectivity between the left posterior cerebellum and the left medial
      orbitofrontal cortex (OFC) (p < 0.05, TFCE corrected). Moreover, the functional
      connectivity between the left posterior cerebellum and the left medial OFC were
      significantly positively correlated with the serum cortisol levels in MDD
      patients. Our results suggest that cerebellar dysconnectivity, in particular
      distributed cerebellar-OFC functional connectivity, may be associated with serum
      cortisol levels in MDD patients.

PMID- 30189326
TI  - Syntactic chameleons: Are there individual differences in syntactic mimicry and
      its possible prosocial effects?
AB  - This study investigated whether syntactic mimicry leads to prosocial effects and
      whether any such effects are modulated by personality traits. Participants and a
      confederate of the experimenters took turns describing simple scenes. Target
      scenes could be described using either a prepositional object or a double object
      dative structure and we tested whether the participants mimicked the structure
      used by the confederate (Experiments 1A and 2A), whether mimicry of the
      participant's sentence structure (Experiments 1B and 2B) made the participant act
      in a more prosocial manner, and whether any such effects vary with Big Five
      traits. Participants displayed significant syntactic mimicry, which was
      additionally negatively related to levels of Extraversion. Syntactic mimicry did
      not lead to more prosocial behavior, as gauged by the time spent on an extra task
      (Experiment 1B). This conclusion was confirmed in Experiment 2B, which used a
      slight adaptation of the task that prevented a ceiling effect. However, a
      positive relation between prosocial behavior and levels of Conscientiousness was
      observed in the mimicry condition, which appeared to invert in the non-mimicry
      condition. We discuss several potential reasons for the absence of prosocial
      effects of syntactic mimicry and provide suggestions for future research.

PMID- 30189327
TI  - Stress, salivary cortisol and periodontitis: A systematic review and meta
      analysis of observational studies.
AB  - OBJECTIVE: This meta-analysis aims to systematically assess whether periodontitis
      has a meaningful effect on salivary cortisol, reflecting changes on free blood
      cortisol levels. DESIGN: The Cochrane Handbook and the PRISMA statement were used
      as reporting guidelines. The MEDLINE-PubMed, Google Scholar, EMBASE, and CENTRAL
      databases were searched until September 2017 to identify eligible studies,
      screened by seven independent authors and verified by an eighth. Studies
      comparing salivary cortisol level of periodontitis cases to controls were
      included. Data were extracted using a predefined table and since all papers were
      non-randomized clinical trials they were appraised using Downs and Black tool.
      DerSimonian random effects meta-analysis was performed using OpenMetaAnalyst.
      RESULTS: Six cross-sectional studies were included, with 258 participants with
      chronic periodontitis and 72 with aggressive periodontitis, in a total of 573
      participants. Overall results showed that aggressive periodontitis patients have,
      on average, 53% higher salivary cortisol levels than healthy controls 1.53 (1.11
      2.12). Meta-regression exploring the relationship among salivary cortisol levels
      and periodontal measures, i.e., periodontitis severity, showed a global neutral
      effect, although this result requires future confirmation due to the low power of
      the model. CONCLUSION: Observational studies results suggest that subjects with
      aggressive periodontitis have higher salivary cortisol levels than healthy ones
      or patients with chronic periodontitis. Such salivary cortisol response
      difference may have a negative impact on the periodontium, contributing to worse
      the burden of aggressive periodontitis disease. In the future, wide and well
      designed longitudinal studies should be carried out in order to extensively
      confirm this possible effect, considering the complex nature of periodontitis and
      its many confounders factors that may contribute to this outcome.

PMID- 30189328
TI  - Venous thromboembolism events following spinal fractures: A single center
      experience.
AB  - OBJECTIVE: Venous thromboembolic events (VTE), including deep venous thrombosis
      (DVT) and pulmonary embolism (PE), are a major cause of readmission, morbidity,
      and mortality after spine surgery. Patients with spinal fractures are
      particularly at an increased risk for VTE. The objective of this study is to
      understand VTE risk factors in this patient population and to examine current
      institutional practices. PATIENTS AND METHODS: We retrospectively examined
      records from 195 consecutive patients with spinal fractures who underwent spinal
      stabilization surgeries- amongst a cohort of 6869 patients who underwent spinal
      surgery. We collected data on patient demographics, surgery, hospital course, and
      30-day rates of VTE, readmission, reoperation. Multivariable logistic regression
      was used to identify independent predictors of each outcome. RESULTS: Among 195
      patients undergoing surgery for spinal fractures, 9.2% experienced a VTE,
      compared to 2.3% among all other spine patients (OR 4.466, p < 0.0001). 48.7%
      spine fracture patients received chemoprophylactic anticoagulation, compared to
      35.7% of all other spine patients (OR 2.657, p < 0.0001). Within 30 days of
      surgery, estimated blood loss (EBL) was associated with VTE (OR 1.001, p =
      0.0415) and DVT (OR 1.001, p = 0.049), and comorbid cardiac disease burden showed
      a trend toward significance in predicting both VTE (OR 1.890, p = 0.0956) and DVT
      (OR 4.228, p = 0.0549). Number of levels in surgery predicted PE within 30 days
      of surgery (OR 1.573, p = 0.0107). CONCLUSIONS: Compared to all other patients
      undergoing spine surgery, patients with spinal fractures are more likely to
      receive chemoprophylactic anticoagulation, but nevertheless have a higher rate of
      VTE events. EBL and comorbid disease burden predict VTE events in patients with
      spine fractures.

PMID- 30189329
TI  - Prussian blue analogues derived iron-cobalt alloy embedded in nitrogen-doped
      porous carbon nanofibers for efficient oxygen reduction reaction in both alkaline
      and acidic solutions.
AB  - Exploring highly active, inexpensive and robust electrocatalysts for oxygen
      reduction reaction (ORR) is of great significance as a competitive alternative to
      noble metal-based catalysts in energy conversion and storage devices. In the
      present study, we design a novel ORR electrocatalyst of iron-cobalt (FeCo) alloy
      nanoparticles embedded on N-doped porous carbon nanofibers (FeCo@PCNF-T) by
      electrospinning of [Polyacrylonitrile (PAN)/Prussian blue analogues/CaCO3] and
      post-calcination treatment. The obtained catalysts with bimetallic active sites
      show unique three-dimensional (3D) hierarchical meso/macropores structures. FeCo
      alloy nanoparticles are encapsulated into graphitic carbon that can increase
      stability and provide additional catalytic active sites. Under the optimized
      condition, FeCo@PCNF-800 displays excellent ORR electrocatalytic activity in
      alkaline solutions, with a more positive half-wave potential (E1/2 of 0.854 V vs
      RHE) and larger limited-diffusion current density (j of 6.012 mA cm-2) than those
      of 20 wt% Pt/C (E1/2 of 0.849 V and j of 5.710 mA cm-2). In addition, FeCo@PCNF
      800 also exhibits comparable ORR electrocatalytic activity in acidic solutions to
      those of 20 wt% Pt/C with onset potential and half-wave potential as more
      positive as 0.843 V vs RHE and 0.739 V vs RHE, respectively. Moreover, FeCo@PCNF
      800 exhibits excellent tolerance towards methanol, stability and a four-electron
      pathway in both basic and acidic solutions. The excellent ORR electrocatalytic
      activity performance of FeCo@PCNF-800 is attributed to the synergistic effect of
      the FeCo alloy nanoparticles and N-doped porous carbon nanofibers. The
      synergistic effect can improve the mass and charge transport capability and
      increase active sites of FeCo-N-C. Furthermore, this work offers a new insight
      for the reasonable design and development of efficient non-noble metal
      electrocatalysts for challenging electrochemical energy-related technologies.

PMID- 30189330
TI  - Spin-orbit effects on the 125Te magnetic-shielding tensor: A cluster-based
      ZORA/DFT investigation.
AB  - Cluster-based calculations of 125Te magnetic-shielding tensors demonstrate that
      inclusion of spin-orbit effects is necessary to obtain the best agreement of
      theoretical predictions with experiment. The spin-orbit contribution to shielding
      depends on the oxidation state and stereochemistry of the 125Te site. Comparison
      of the performance of various density functionals indicates that GGA functionals
      behave similarly to each other in predicting NMR magnetic shielding. The use of
      hybrid functionals improves the predictive ability on average for a large set of
      125Te-containing materials. The amount of Hartree-Fock exchange affects the
      predicted parameters. Inclusion of larger Hartree-Fock exchange contributions in
      hybrid functionals results in larger slopes of the correlation between calculated
      magnetic-shielding and experimental chemical-shift principal components, by 10
      15% from the ideal value.

PMID- 30189331
TI  - Antimicrobial resistance and genotypic characteristics of Listeria monocytogenes
      isolated from food in Poland.
AB  - The aim of the study was to determine antimicrobial resistance and genotypic
      characteristics of L. monocytogenes isolated from food of animal origin from
      different parts of Poland during years 2013-2016. A total of 146 isolates were
      tested using a microbroth dilution method, whereas virulence genes and molecular
      serogroups were identified by PCR. Pulsed-field gel electrophoresis (PFGE) and
      multilocus sequence typing (MLST) methods were used to analyze the genotypic
      relationship of the strains. Altogether, 102 pulsotypes grouped into 7 clusters
      and 24 sequence types, including 3 new types, were identified. Most of the
      strains clustered into individual patterns were originated from different food
      products and were isolated in different geographical regions at various time. L.
      monocytogenes was mostly resistant to oxacilin (90.4% strains), clindamycin
      (54.1%) and ceftriaxone (49.3%). A multiresistance patterns, mainly to
      ceftriaxone, oxacillin together with other antimicrobials, were observed among
      27.4% strains. Antimicrobial resistance and presence of virulence genes suggest
      that food of animal origin contaminated with L. monocytogenes may present a risk
      for public health.

PMID- 30189332
TI  - Global gray matter morphometry differences between children with reading
      disability, ADHD, and comorbid reading disability/ADHD.
AB  - Extensive, yet disparate, research exists elucidating structural anomalies in
      individuals with Reading Disability (RD) or ADHD. Despite ADHD and RD being
      highly comorbid, minimal research has attempted to determine shared patterns of
      morphometry between these disorders. In addition, there is no published research
      examining the morphometry of comorbid RD and ADHD (RD/ADHD). Hence, we conducted
      voxel-based morphometry on the MRI scans of 106 children, ages 8-12 years, with
      RD, ADHD, or RD/ADHD, and typically developing controls. We found right caudate
      and superior frontal regions in both RD and ADHD, along with areas specific to RD
      and to ADHD that are consistent with current theories on these disorders. Perhaps
      most importantly, we found a potential neurobiological substrate for RD/ADHD.
      Further, our findings illustrate both shared and specific contributors to
      RD/ADHD, supporting two current theories on the comorbidity of RD and ADHD,
      thereby facilitating future work on potential etiologies of RD/ADHD.

PMID- 30189333
TI  - Targeting head movements in humans: Compensation for disturbance from
      simultaneous body rotations.
AB  - Vestibular information plays an important role in spatially oriented motor
      control and perception. With regard to reorienting head movements, little is
      known of (1) how vestibular mechanisms compensate for disturbances from
      concurrent passive trunk rotations (e.g. in a veering vehicle), and (2) whether
      and how this disturbance compensation is related to the perception of body
      orientation in space. We here address these two questions in a single experiment.
      Six healthy subjects (Ss) seated on a turning chair in darkness performed two
      tasks. (1) Head pointing: Ss made swift head movements in darkness towards the
      angular position in space of a previously shown visual target. These movements
      were disturbed by concurrent rotations of the chair, and hence the trunk, which
      were driven by scaled down versions of the Ss' own head-on-trunk rotations.
      Although unaware of the disturbance, Ss adjusted their head movements so as to
      attenuate its effect on head-in-space (HS) position by about 45%. (2) Visual
      straight ahead (VSA): Using a light pointer, Ss indicated their VSA before each
      head-pointing trial and tried to reproduce it after the trial. In all Ss, VSA
      accounted for the disturbing trunk rotation, although to individually varying
      degrees. No correlation could be detected between VSA reproduction and motor
      performance, neither within nor across subjects. A vestibular loss subject who
      performed the same two tasks made no compensatory movements during head pointing
      and did not account for the disturbance of his HS position during VSA
      reproduction. Three concepts of vestibular information processing for head
      movement control were explored with regard to their compatibility with the head
      pointing results: (1) Conventional negative feedback, (2) Interaction with an
      efference copy, and (3) Interaction with neck proprioceptive information.
      Theoretical analyses and model simulations indicated that all three concepts can
      explain the observed disturbance compensation. However, they differ in terms of
      control stability in the presence of feedback time delays, with (3) being best
      and (1) worst. The different concepts might correspond to fast simple and slower
      complex compensation mechanisms, respectively, and possibly complement each other
      during natural behaviours. VSA reproduction may be based on analogous processing
      principles, but appears to involve different neural circuitries.

PMID- 30189334
TI  - Development of quantum dot aptasensor and its portable analyzer for the detection
      of di-2-ethylhexyl phthalate.
AB  - We have developed a quantum dot aptasensor (QD-aptasensor) and its accompanying
      portable analyzer for the detection of di-2-ethylhexyl phthalate (DEHP). This
      sensor is based on a newly screened aptamer (60-mer) via SELEX and shows a
      binding affinity of 213 nmol/L with DEHP. The 60-mer aptamer together with its
      three shorter truncated aptamers (45, 28, and 22-mer) as well as three different
      DNA probes (12, 9, and 13-mer) were further investigated to form the best
      combination for the QD-aptasensor. Using a 22-mer-truncated aptamer and a 12-mer
      DNA probe combination, the QD-aptasensor demonstrated excellent DEHP sensitivity
      with an LOQ = 0.5 pg/mL as well as good selectivity in the presence of other
      phthalate analogs. The binding between the truncated aptamers and DEHP was also
      characterized. Finally, a QD-aptasensor-based portable analyzer was also
      developed, and its equivalence to the laboratory protocol was established with a
      correlation coefficient r = 0.86 for DEHP concentrations ranging from 0.0005 to
      100 ng/mL.

PMID- 30189335
TI  - Impedance detection integrated with dielectrophoresis enrichment platform for
      lung circulating tumor cells in a microfluidic channel.
AB  - Enrichment and detection of rare cells are essential in many biological and
      medical applications. In this study, circulating tumor cells were detected by
      combining dielectrophoretic (DEP) manipulation and impedance measurement using
      circular microelectrodes within a single microfluidic device. A prototype of the
      device was fabricated through standard soft-lithography. With the proposed
      microchip, target cells (lung cancer cells, A549) were guided toward the center
      of the working region due to the action of positive DEP and hydrodynamic drag
      forces and were then trapped onto the desired sensing electrodes. Impedance was
      measured to identify the presence of cells. Impedance spectroscopy was conducted
      at different numbers of cells. Linear characteristics were found using
      differential analysis technique. Experimental results showed that the impedance
      sensor can detect A549 cell line with low cell number at the appropriate
      frequencies. Limit of detection (LOD) of approximately 3 cells was achieved at
      frequencies near 50 kHz. This simple, rapid, label-free, and low-cost approach
      may open up new opportunities for developing cell diagnosis systems for future
      applications.

PMID- 30189337
TI  - Attributes and antecedents of frequent attendance in health care systems: Comment
      on Kivela et al., 2018.

PMID- 30189336
TI  - Padua FIXa resistance to Protein S and a potential therapy for hyperactive FIXa.
AB  - INTRODUCTION: Abnormalities in the levels and functions of proteins that maintain
      hemostasis can cause thrombosis. Factor IX (FIX) R338L, i.e., Factor IX Padua, is
      a hyperactive clotting factor that promotes thrombosis. The R338L mutation
      increases the clotting rate by 8-fold despite increasing the Factor IXa enzymatic
      activity by only 2-fold. Protein S (PS) is a natural anticoagulant that directly
      inhibits FIXa. Because individuals affected by the R338L mutation have normal
      concentrations of PS, we speculated that the Padua hypercoagulation phenotype is
      due to decreased inhibition of FIXa R338L by PS. METHODS: We measured the ability
      of PS to inhibit FIX R338L, and we assessed the ability of PS to mitigate the
      prothrombotic effect FIX R338L. RESULTS: Plasma clotting assays demonstrated that
      3-fold more PS was required to inhibit FIXa R338L compared with inhibition of
      wild type FIXa. Thrombin generation assays with Padua patient plasma
      recapitulated this biochemical consequence of the R338L mutation. Importantly,
      the less efficient inhibition of FIXa R338L was reversed by increasing PS
      concentration. Binding and co-immunoprecipitation studies revealed that the
      decrease in the inhibition of FIXa R338L by PS was caused by a 3- to 4-fold
      reduction in FIXa R338L affinity for PS. CONCLUSION: In summary, the resistance
      of FIXa R338L to inhibition by PS likely contributes to the unexpectedly high
      clotting rate in Padua individuals. Moreover, PS-mediated reversal of the
      pathological properties of FIXa R338L suggests that PS administration may be a
      novel and effective means to mitigate thrombophilia caused by any source of
      elevated FIXa activity.

PMID- 30189338
TI  - Lack of improvement in multiplication is associated with reverting from verbal
      retrieval to numerical operations.
AB  - Models of the neural basis of arithmetic argue that left inferior frontal cortex
      is involved in cognitive control of verbal representations of math facts in left
      lateral temporal cortex, whereas bilateral intra-parietal cortex is involved in
      numerical calculation. Lower levels of math competence for multiplications is
      associated with greater effortful retrieval because of less robust verbal
      representations and the engagement of numerical operations as a back-up strategy.
      Previous studies on multiplication have focused on brain activation in isolated
      nodes of the network, so we do not know how functional connectivity between these
      nodes is related to competence. Moreover, previous studies have not employed
      longitudinal designs, so we do not know how changes in multiplication performance
      over time is related to changes in its neural basis. The objective of this study
      was to investigate how changes in multiplication task performance is associated
      with changes in functional connectivity of temporal cortex with frontal and
      parietal cortices. Longitudinal data was collected from 45 children, with an
      average 2.2-year interval between the two sessions, when they were about 11 years
      old at time 1 (T1) and 13 years old at time 2 (T2). A Psychophysiological
      Interaction (PPI) analysis was carried out by defining the seed in the temporal
      cortex (i.e. posterior superior and middle temporal gyri) and examining changes
      in connectivity with frontal cortex (i.e. left inferior frontal gyrus) as well as
      parietal cortex (i.e. left and right inferior and superior parietal lobules). We
      found that children who did not improve in a multiplication task showed greater
      levels of functional connectivity of left temporal cortex with left inferior
      frontal gyrus (IFG) and left intraparietal sulcus (IPS) at T2, as compared to
      their peers who improved. The cluster showing greater levels of connectivity in
      the left IFG at T2 for the Non-improvers overlapped a cluster independently
      identified by a verbal localizer task and the cluster showing greater levels of
      connectivity in the left IPS Non-improvers overlapped a cluster independently
      identified by a numerosity localizer task. These results suggest that lack of
      improvement in multiplications are associated with greater cognitive control of
      verbal representations and greater engagement of numerical operations.

PMID- 30189340
TI  - Evidence for a spinal involvement in temporal pain contrast enhancement.
AB  - Spatiotemporal filtering and amplification of sensory information at multiple
      levels during the generation of perceptual representations is a fundamental
      processing principle of the nervous system. While for the visual and auditory
      system temporal filtering of sensory signals has been noticed for a long time,
      respective contrast mechanisms within the nociceptive system became only recently
      subject of investigations, mainly in the context of offset analgesia (OA)
      subsequent to noxious stimulus decreases. In the present study we corroborate in
      a first experiment the assumption that offset analgesia involves a central
      component by showing that an OA-like effect accounting for 74% of a corresponding
      OA reference can be evoked by decomposing the stimulus offset into two separate
      box-car stimuli applied within the same dermatome but to separate populations of
      primary afferent neurons. In order to draw conclusions about the levels of the
      CNS at which temporal filtering of nociceptive information takes place during OA
      we investigate in a second experiment neuronal activity in the spinal cord during
      a painful thermal stimulus offset employing high-resolution fMRI in healthy
      volunteers. Pain-related BOLD responses in the spinal cord were significantly
      reduced during OA and their time course followed widely behavioral hypoalgesia,
      but not the thermal stimulation profile. In summary, the results suggest that
      temporal pain contrast enhancement during OA comprises a central mechanism and
      this mechanism becomes already effective at the level of the spinal cord.

PMID- 30189341
TI  - Corpus callosum microstructure is associated with motor function in preschool
      children.
AB  - The preschool period is a time of significant physical and behavioral growth,
      including the improvement of gross and fine motor skills. Although motor
      development has been comprehensively mapped from infancy to adulthood, the neural
      correlates associated with motor advancements during early childhood remain
      unclear. The current study used diffusion tensor imaging (DTI) to delineate key
      motor pathways and characterize their relationships with motor performance in 80
      typically developing preschool children, aged 3-6 years. The Movement Assessment
      Battery for Children-2nd edition (MABC-II) was used to assess motor functioning.
      Partial correlations between DTI parameters and motor performance, controlling
      for sex and age, revealed a positive correlation between motor performance and
      fractional anisotropy of corpus callosum motor fibers, as well as negative
      correlations of motor performance with mean and radial diffusivity. These results
      appear to be driven by females, as correlations were significant in girls but not
      boys when analyzed separately. Mean corticospinal tract (CST) diffusion
      parameters were not significantly related to motor performance, but relationships
      were observed at regionally specific locations along the bilateral CST. These
      findings suggest preschool-aged children with better motor performance show more
      mature white matter patterns within motor pathways, and that the structural
      variation in these pathways may partially account for the natural variability in
      motor performance.

PMID- 30189342
TI  - Childhood adversity as a transdiagnostic risk factor for affective disorders in
      adulthood: A systematic review focusing on biopsychosocial moderating and
      mediating variables.

PMID- 30189343
TI  - Type 1 innate lymphoid cells are associated with type 2 diabetes.
AB  - AIM: Type 1 innate lymphoid cells (ILC1s) play a major role in regulating
      systemic inflammatory diseases. However, the relationship between ILC1s and type
      2 diabetes (T2D) remains unclear. Thus, the present study investigated the
      relationship between ILC1s and glucose homoeostasis in humans. METHODS: A total
      of 37 newly diagnosed T2D patients and 32 subjects with normal glucose tolerance
      (NGT), matched for age and body mass index (BMI), were enrolled in the study.
      Flow cytometric analysis of ILC1s derived from peripheral blood mononuclear cells
      (PBMCs) and omental adipose tissue was performed. RESULTS: T2D patients displayed
      greater numbers and frequencies of circulating and adipose tissue ILC1s (P <
      0.05) compared with NGT subjects, and the two types of ILC1s correlated
      positively with each other. Circulating ILC1s were positively associated with
      glycated haemoglobin (HbA1c), fasting plasma glucose (FPG), homoeostasis model
      assessment for insulin resistance (HOMA-IR), adipose tissue insulin resistance
      index (Adipo-IR) and serum free fatty acids (FFAs). A logistic regression model
      revealed that patients with higher ILC1 levels exhibited a 13.481-fold greater
      risk of developing T2D. CONCLUSION: This study is the first to provide evidence
      that ILC1 abnormalities are involved in the development of diabetes. The data
      also suggest a potential role of ILC1s as therapeutic indicators in the treatment
      of T2D.

PMID- 30189339
TI  - Adolescents' brain-autonomic coupling during emotion processing.
AB  - Autonomic nervous system (ANS) activity is a core component of emotion
      processing. The limbic system and medial prefrontal cortex play important roles
      in the regulation of ANS activity. However, the integration of brain activity and
      ANS activity has yet to be investigated in adolescents despite independent
      evidence of adolescents' heightened neural and physiological sensitivity to
      emotional stimuli. The present study examined the relations of ANS activity in
      the parasympathetic nervous system (PNS) and sympathetic nervous system (SNS)
      with brain activity during emotional face processing in adolescents. 135
      adolescents (65 female; M = 17.15 yr, SD = 0.42) completed an emotional faces
      task during an fMRI scan while electrocardiography and skin conductance were
      recorded simultaneously. Using linear mixed-effect modelling, we tested the
      effect of change in respiratory sinus arrhythmia (RSA), a measure of PNS
      activity, and number of skin conductance responses (SCRs), a measure of SNS
      activity, on neural activity while adolescents viewed emotional faces. Greater
      RSA withdrawal, indicating decreased PNS activity, was associated with increased
      activation in the ventromedial prefrontal cortex (vmPFC). More SCRs, indicating
      greater SNS activity, were associated with decreased activation in several
      regions including the dorsomedial prefrontal cortex and increased activation in
      the left hippocampus. Left hippocampus-SCR coupling and vmPFC-RSA coupling
      predicted baseline SCR and RSA respectively. These findings implicate the
      hippocampus for potentiating SNS activity, document that regulation of SNS and
      PNS activity are coordinated with distinct regions of the medial prefrontal
      cortex, and suggest potential developmental differences in vmPFC regulation of
      PNS activity between adolescents and adults.

PMID- 30189344
TI  - Obstructive sleep apnoea syndrome in patients living with diabetes: Which
      patients should be screened?
AB  - AIM: Because type 2 diabetes (T2D) is related to obesity, it is often associated
      with obstructive sleep apnoea syndrome (OSAS), although OSAS is also frequently
      diagnosed in patients with type 1 diabetes (T1D) and may promote gestational
      diabetes. Thus, this systematic review of the scientific evidence aimed to
      evaluate the epidemiological association between OSAS and all forms of diabetes,
      the current understanding of the pathophysiological mechanisms behind these
      associations, the expected benefits and limitations of OSAS treatment in patients
      with diabetes and, finally, to propose which patients require screening for OSAS.
      METHODS: A panel comprising French expert endocrinologists and pneumologists was
      convened. Two of these experts made a search of the relevant literature for each
      subpart of the present report; all panel experts then critically reviewed the
      entire report separately as well as collectively. RESULTS: There is little
      evidence to support the notion that OSAS treatment improves glycated haemoglobin,
      although it may improve nighttime blood glucose control and insulin sensitivity.
      However, there is robust evidence that OSAS treatment lowers 24-h blood pressure.
      CONCLUSION: The high prevalence of OSAS in patients with T1D and T2D justifies
      screening for the syndrome, which should be based on clinical symptoms, as the
      benefits of OSAS treatment are mainly improvement of symptoms related to sleep
      apnoea. There are also several clinical situations wherein screening for OSAS
      seems justified in patients with diabetes even when they have no symptoms,
      particularly to optimalize control of blood pressure in cases of resistant
      hypertension and microvascular complications.

PMID- 30189345
TI  - Oxytocin administration and emotion recognition abilities in adults with a
      history of childhood adversity.
AB  - Adverse childhood experience such as neglect or abuse can lead to long-term
      deficits in emotion processing abilities. Animal studies indicate that oxytocin
      production and/or sensitivity are influenced by variation in early nurturing
      experiences. The goal of this study was to test whether emotion recognition
      abilities and empathy might be improved via intranasal oxytocin administration in
      adults with a history of childhood maltreatment. We assessed a total of 80
      healthy participants, half with and half without a history of childhood
      adversity. Participants performed the Reading the Mind in the Eyes Test (RMET)
      and an emotion recognition task under 24 IU intranasal oxytocin and placebo,
      using a double-blind crossover study design. In the first of two sessions, both
      groups profited equally form oxytocin administration and showed greater accuracy
      under oxytocin compared to placebo in the RMET (p = .049). In the emotion
      recognition task, only the early adversity group benefited significantly from
      oxytocin administration in the first session (p = .035), mainly due to more
      accurate recognition of angry and fearful facial expression. Our findings show
      that emotion processing abilities might be improved via oxytocin administration
      in adults reporting adverse childhood experiences.

PMID- 30189347
TI  - Opioid receptors in the GI tract: targets for treatment of both diarrhea and
      constipation in functional bowel disorders?
AB  - Opioids have been used for centuries, mostly as a sedative and to treat pain.
      Currently, they are used on a global scale for the treatment of acute and chronic
      pain in diseases as osteoarthritis, fibromyalgia, and low back pain. Binding of
      opioids on opioid receptors can cause a range of different effects such as
      changes in stress response, analgesia, motor activity and autonomic functions.
      This review provide a synthetic summary of the most recent literature on the use
      of drugs acting on mu-receptors to treat two prevalent functional bowel
      disorders, presenting with opposite bowel habit. Eluxadoline and naloxegol,
      methylnaltrexone and naldemedine are recently FDA and/or EMA approved drugs
      demonstrated to be effective and safe for treatment respectively of irritable
      bowel syndrome subtype diarrhea and opioid induced constipation.

PMID- 30189346
TI  - Genetic and phytochemical investigations for understanding population variability
      of the medicinally important tree Saraca asoca to help develop conservation
      strategies.
AB  - Saraca asoca (Roxb.) De Wilde (Caesalpiniaceae) is a highly traded IUCN red
      listed tree species used in Ayurvedic medicines for the treatment of various
      disorders, especially gynaecological problems. However, information about the
      genetic variations between populations and corresponding variation in specialized
      metabolites of S. asoca remains unclear. To address this issue, we analysed 11
      populations of S. asoca with 106 accessions collected from Western Ghats of India
      using ISSR markers along with selected phytocompounds using RP-HPLC. Twenty
      primers were screened, out of which seven were selected for further analysis
      based on generation of clear polymorphic banding patterns. These seven ISSR
      primers produced 74 polymorphic loci. AMOVA showed 43% genetic variation within
      populations and 57% among the populations of S. asoca. To estimate the genetic
      relationships among S. asoca populations, UPGMA and Bayesian Models were
      constructed, which revealed two clusters of similar grouping patterns. However,
      excluding minor deviations, UPGMA and dissimilarity analysis showed close
      association of genotypes according to their geographical locations. Catechin
      (CAT), epicatechin (EPI) and gallic acid (GA) were quantified from bark and leaf
      samples of corresponding genotypes collected from 106 accessions. ROC plots
      depicted the sensitivity and specificity of the concentrations of tested
      phytocompounds at various cut-off points. Although, multiple logistic regression
      analysis predicted some association between few loci with GA, EPI and CAT, but
      PCA for phytochemical data failed to distinguish the populations. Overall, there
      were no significant trends observed to distinguish the populations based on these
      phytocompounds. Furthermore, the study advocates the delineate provenance regions
      of S. asoca genotypes/chemotype snapshots for in-situ conservation and ex-situ
      cultivation.

PMID- 30189348
TI  - The influence of eukaryotic chromatin state on CRISPR-Cas9 editing efficiencies.
AB  - CRISPR/Cas technologies have rapidly become in routine use for site-directed
      genetic or transcriptional manipulation. Despite this, the efficiency of
      CRISPR/Cas9 functioning cannot entirely be predicted, and it is not fully
      understood which factors contribute to this variability. Recent studies indicate
      that heterochromatin can negatively affect Cas9 binding and functioning.
      Investigating chromatin factors indicates that DNA cytosine-5 methylation does
      not directly block Cas9 binding. Nucleosomes, however, can completely block Cas9
      access to DNA in cell-free assays and present a substantial hurdle in vivo. In
      addition to being associated with an open chromatin state, active transcription
      can directly stimulate DNA cleavage by influencing Cas9 release rates in a strand
      specific manner. With these insights and a better understanding of genome-wide
      chromatin and transcription states, CRISPR/Cas9 effectiveness and reliability can
      be improved.

PMID- 30189349
TI  - Tomorrow today: organ-on-a-chip advances towards clinically relevant
      pharmaceutical and medical in vitro models.
AB  - Organ-on-a-chip technology offers the potential to recapitulate human physiology
      by keeping human cells in a precisely controlled and artificial tissue-like
      microenvironment. The current and potential advantages of organs-on-chips over
      conventional cell cultures systems and animal models have captured the attention
      of scientists, clinicians and policymakers as well as advocacy groups in the past
      few years. Recent advances in tissue engineering and stem cell research are also
      aiding the development of clinically relevant chip-based organ and diseases
      models with organ level physiology for drug screening, biomedical research and
      personalized medicine. Here, the latest advances in organ-on-a-chip technology
      are reviewed and future clinical applications discussed.

PMID- 30189350
TI  - Do trace metal contamination and parasitism influence the activities of the
      bioturbating mud shrimp Upogebia cf. pusilla?
AB  - Mud shrimp are considered as among the most influential ecosystem engineers in
      marine soft bottom environments because of their significant bioturbation
      activity and their high density. These organisms play a key role on the physical
      structure of sediments through intense sediment reworking activity and also
      deeply influence geochemical properties of sediments via frequent bioirrigation
      events. The influence that mud shrimp have on the environment is related to the
      magnitude of bioturbation processes and subsequently depends on their
      physiological condition. In natural environments, several factors act together
      and influence the well-being of organisms. Among them, the deleterious role of
      parasites on the physiology and the behavior of their host is well established.
      Aquatic organisms are also subject to pollutants released by anthropogenic
      activities. However, the effect of both stressors on the fitness and bioturbation
      activity of mud shrimp has never been investigated yet. We conducted a 14-day ex
      situ experiment to evaluate the influence of trace metal contamination (cadmium
      Cd) and parasitism infestation on the gene expression (molecular endpoint) and
      sediment reworking activity (behavioral endpoint) of the mud shrimp Upogebia cf.
      pusilla. At completion, mud shrimp exhibited substantial Cd bioaccumulation, with
      parasitized organisms showing a significantly lower contaminant burden than
      unparasitized specimens. Cadmium contamination induces modifications of gene
      expression in both unparasitized and parasitized organisms. We report an
      antagonistic effect of both stressors on gene expression, which cannot be fully
      explained by a lower Cd bioaccumulation. At the behaviour level, parasitism seems
      to reduce the sediment reworking activity of mud shrimp, while Cd contamination
      appears to stimulate this activity. This study highlights that the effects of
      multiple stressors may be quite different from the effects of each stressor
      considered individually. It should also motivate for more studies evaluating the
      influence of multiple stressors on different endpoints encompassing various
      levels of organization.

PMID- 30189353
TI  - Corrigendum to "Taxonicity and network structure of generalized anxiety disorder
      and major depressive disorder: An admixture analysis and complex network
      analysis." [Journal of Affective Disorders, 199 (2016) 99-105].

PMID- 30189351
TI  - Comparative transcriptome analysis between the short-term stress and long-term
      adaptation of the Ruditapes philippinarum in response to benzo[a]pyrene.
AB  - In order to monitor the pollution of polycyclic aromatic hydrocarbons (PAHs) in
      the seawater environment, screening biomarkers capable of monitoring PAHs is the
      focus of many studies. The transcriptomic profiles of the digestive gland tissue
      from the R. philippinarum groups after the exposure to BaP (4 MUg/L) at four time
      points (0, 0.5, 6 and 15 days) were investigated to globally screen the key genes
      and pathways involved in the responses to short-term stress and long-term
      adaptation of BaP resistance. By comparative transcriptome analysis, 233, 282 and
      58 differentially expressed genes (DEGs) were identified at 0.5 day, 6 day and 15
      day (vs 0 day). The differential expression genes were related to stress
      response, detoxification metabolic process and innate immunity. DEGs of each
      group at different stages were clustered in six profiles based on gene expression
      pattern. Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG)
      pathway analysis were used on all genes to determine the biological functions and
      processes. We selected Multidrug resistance protein 3 (MRP3), transcriptional
      regulator ATRX-like isoform X2 (ATRX) as biomarker indicator genes for short-term
      pollution monitoring and NADH dehydrogenase [ubiquinone] 1 (NQO1), Complement C1q
      like protein 4 (C1q), Glutathione-S-transferase theta (GST), E3 ubiquitin-protein
      ligase (E3) for long-term pollution monitoring based on the different expression
      patterns and the function in detoxification and antioxidant defense system.
      Besides, the expression of seven genes was measured through Quantitative real
      time PCR (qPCR) according to their gene expression patterns which was confirmed
      by the DGE analysis. Taken together, adoption of transcriptomic analysis to
      explore the bivalves' mRNA abundance changes and detoxification metabolic
      mechanism under the BaP stress at different time points can aid the development
      of sensitive and informed molecular endpoints for application towards
      ecotoxicogenomic monitoring of bivalves.

PMID- 30189354
TI  - Prevalence of late-life depression and its correlates in a community-dwelling low
      educated population aged 75+ years: The Pieta study.
AB  - BACKGROUND: The number of individuals with advanced age is growing worldwide,
      especially in developing countries. Depression is the most common mental disorder
      in the elderly. The aim of this study was to evaluate the prevalence rates and
      the correlates of late-life depression (LLD) and clinically significant
      depressive symptoms (CSDS) in a population aged 75+ years. METHODS: We evaluated
      639 community-dwelling individuals aged 75+ years in Caete (MG), Brazil, and used
      the MINI to diagnose LLD according to DSM-IV criteria and the GDS-15 to identify
      CSDS. Quality of life was assessed by the WHOQOL-OLD scale. RESULTS: Overall, 639
      individuals (64% female, with a mean age of 81.1 +/- 5.2 and 2.6 +/- 2.8 years of
      schooling) were evaluated; 70 (11.1%) were diagnosed with LLD and 146 (25.6%)
      with CSDS. Depressed subjects (both with LLD and CSDS) had poorer measures of
      quality of life. Logistic regression analyses showed that LLD was independently
      associated to a history of falls/fracture, a diagnosis of cognitive impairment-no
      dementia, the number of regular drugs used, lack of reading habit and, inversely,
      to systolic blood pressure. LIMITATIONS: The use of MINI which has not been
      validated in the elderly. No information was available on the number of previous
      depressive episodes or on the age of first episode. CONCLUSION: Both dimensional
      and categorical diagnoses of depression were prevalent among community-dwelling
      oldest-old individuals. Different clinical and personal variables were associated
      with depression, which negatively influenced the quality of life of the affected
      individuals.

PMID- 30189352
TI  - Adverse effects of two pharmaceuticals acetaminophen and oxytetracycline on life
      cycle parameters, oxidative stress, and defensome system in the marine rotifer
      Brachionus rotundiformis.
AB  - To investigate the adverse effect of two widely used pharmaceuticals, paracetamol
      (acetaminophen [APAP]) and oxytetracycline (OTC) on the marine rotifer Brachionus
      rotundiformis (B. rotundiformis), the animals were exposed to various
      environmentally-relevant concentrations. Up to date, acetaminophen and
      oxytetracycline have been considered as toxic, if used above threshold
      concentration, i.e. overdosed. However, this study demonstrated these two
      pharmaceuticals even at low concentration (i.e., MUg/L scale) elicited oxidative
      stress through the generation of reactive oxygen species (ROS) along with the
      increased glutathione S-transferase activity, despite no-observed effect in in
      vivo population growth. To validate the adverse effects of the two
      pharmaceuticals at relatively low concentrations, mRNA expression analysis was
      performed of the entire set of genes encoding 26 cytochrome P450s (CYPs) of phase
      I and 19 glutathione S-transferases (GSTs) of phase II of the rotifer B.
      rotundiformis. The mRNA expression analysis suggested specific genes CYP3045A2
      and GSTsigma1, GSTsigma4, and GSTomega1 take part in detoxification of APAP and
      OTC, resulting in no significant changes in the population growth and
      undetermined no observed effect concentration (NOEC) in the marine rotifer B.
      rotundiformis.

PMID- 30189356
TI  - Histologically proven acute tubular necrosis in a series of 27 ICU patients.
AB  - PURPOSE: Since renal biopsy is rarely performed for identifying acute tubular
      necrosis in ICU patients, there is little information on the real
      histopathological abnormalities observed in such situations. MATERIALS AND
      METHODS: The clinical data of 27 patients with a confirmed diagnostic of acute
      tubular necrosis issued from two recent series gathering 125 patients who had
      renal biopsy during their ICU stay were reviewed. They were divided into sepsis
      (n = 14) and non-sepsis (n = 13) groups. Histopathologic lesions were reanalyzed
      and semi-quantitatively graded by a pathologist without knowledge of clinical
      characteristics of the patients. RESULTS: SAPS2 and SOFA scores were identical in
      the two groups. Half of the patients had neither sepsis nor shock. The
      histopathological score was higher in the septic than in the non-septic group: 9
      [IC; 9-11] vs 7 [IC 5.25-8.75]; p = 0.01. There was no striking histopathological
      difference between septic and non-septic patients. However, the cytotoxic edema
      score was higher (3 [1; 3] vs 1 [0; 1]; p = 0.006), and interstitial infiltration
      with polymorphonuclears was more frequent (p = 0.02) in septic than in non-septic
      patients. CONCLUSIONS: Septic and non-septic ICU patients with ATN had similar
      histopathologic features but lesions were more severe than in septic than in non
      septic patients.

PMID- 30189357
TI  - Guided tissue organization and disease modeling in a kidney tubule array.
AB  - Three-dimensional (3D) in vitro kidney tubule models have either largely relied
      on the self-morphogenetic properties of the mammalian cells or used an engineered
      microfluidic platform with a monolayer of cells cultured on an extracellular
      matrix (ECM) protein coated porous membrane. These systems are used to understand
      critical processes during kidney development and transport properties of renal
      tubules. However, high variability and lack of kidney tubule-relevant geometries
      among engineered structures limit their utility in disease research and pre
      clinical drug testing. Here, we report a novel bioengineered guided kidney tubule
      (gKT) array system that incorporates in vivo-like physicochemical cues in 3D
      culture to reproducibly generate homogeneous kidney tubules. The system utilizes
      a unique 3D micro-molded ECM platform in human physiology-scale dimensions (50
      MUm diameter) and relevant shapes to guide cells towards formation of mature
      tubule structures. The guided kidney tubules in our array system display enhanced
      tubule homogeneity with in vivo-like structural and functional features as
      evaluated by marker protein localization and epithelial transport analysis.
      Furthermore, the response of gKT structures to forskolin treatment exhibits
      characteristic tissue transformations from tubules to expanding cysts. Moreover,
      acute cisplatin injury causes induction of Kidney Injury Molecule-1 (KIM-1)
      expression as well as tubular necrosis and apoptosis. Thus the gKT array system
      offers enhanced structural uniformity with accurate in vivo-like tissue
      architecture, and will have broad applications in kidney tubule disease
      pathophysiology (including ciliopathies and drug-induced acute kidney injury),
      and will enhance pre-clinical drug screening studies.

PMID- 30189355
TI  - Is teachers' mental health and wellbeing associated with students' mental health
      and wellbeing?
AB  - BACKGROUND: Factors within the school environment may impact young people's
      mental health and wellbeing. The aim of this study was to understand the
      association between teacher and student mental health and wellbeing. Further, it
      seeked to identify possible explanations by examining whether the strength of any
      association is weakened once quality of teacher-student relationships, teacher
      presenteeism and absence are considered. METHODS: Cross-sectional data were
      collected from 3216 year 8 (aged 12-13 years) students and from 1182 teachers in
      25 secondary schools in England and Wales. The association between teacher
      wellbeing (measured by Warwick Edinburgh Mental Wellbeing Scale (WEMWBS)) with
      student wellbeing (WEMWBS) and with student psychological distress (Total
      Difficulties Score (TDS)) was assessed using Random Effects Mixed Models.
      Analyses were repeated using teacher depression (measured by Patient Health
      Questionnaire) as the explanatory variable. RESULTS: Better teacher wellbeing was
      associated with i) better student wellbeing (standardised effect = 0.07, 95% CI =
      0.02 to 0.12) and ii) lower student psychological distress (standardised effect =
      -0.10, 95% CI = -0.16 to -0.04). Teacher presenteeism and the quality of the
      teacher-student relationship appeared to be on the pathway of these
      relationships. Higher levels of teacher depressive symptoms were associated with
      poorer student wellbeing and psychological distress (standardised effect = -0.06,
      95% CI = -0.11 to -0.01 & 0.09, 95% CI = 0.03 to 0.15). This association did not
      withstand adjustment for teacher presenteeism. LIMITATIONS: Cross sectional in
      design so unable to establish temporal associations. CONCLUSIONS: Associations
      were found between teacher wellbeing and student wellbeing and psychological
      distress. There were also an association between teacher depression and student
      wellbeing. Both may be partially explained by teacher presenteeism and quality of
      teacher-student relationships.

PMID- 30189358
TI  - Biodegradable and elastomeric vascular grafts enable vascular remodeling.
AB  - Implanted grafts, including vascular substitutes, inevitably experience
      remodeling by host cells. The design of grafts capable of promoting constructive
      remodeling remains a challenge within regenerative medicine. Here, we used a
      biodegradable elastic polymer, poly (l-lactide-co-epsilon-caprolactone) (PLCL),
      to develop a vascular graft with circumferentially aligned microfibers. The
      grafts exhibited excellent handling properties and resistance to deformation.
      Upon implantation in rat abdominal aorta, graft-guided neoartery regeneration was
      achieved in a short period (4 weeks) as evidenced by rapid cell infiltration and
      alignment, and complete endothelialization. During vascular remodeling, a high
      ratio of M2/M1 macrophage was detected, and the expression of pro-inflammatory
      and anti-inflammatory cytokines first increased and then decreased to normal
      level for the follow-up period. By 12 months, the PLCL grafts were almost
      completely degraded and a well-integrated neoartery was formed with
      characteristics comparable to native arteries, such as transparent appearance,
      synchronous pulsation, dense and orderly extracellular matrix (ECM) arrangement,
      strong and compliant mechanical properties, and vasomotor response to
      pharmacologic agents. Taken together, our strategy represents a new avenue for
      guided tissue regeneration by designing the grafts to promote tissue remodeling
      via controlling structure, degradation and mechanical properties of the
      scaffolds.

PMID- 30189359
TI  - AXL Mediates Esophageal Adenocarcinoma Cell Invasion through Regulation of
      Extracellular Acidification and Lysosome Trafficking.
AB  - Esophageal adenocarcinoma (EAC) is a highly aggressive malignancy that is
      characterized by resistance to chemotherapy and a poor clinical outcome. The
      overexpression of the receptor tyrosine kinase AXL is frequently associated with
      unfavorable prognosis in EAC. Although it is well documented that AXL mediates
      cancer cell invasion as a downstream effector of epithelial-to-mesenchymal
      transition, the precise molecular mechanism underlying this process is not
      completely understood. Herein, we demonstrate for the first time that AXL
      mediates cell invasion through the regulation of lysosomes peripheral
      distribution and cathepsin B secretion in EAC cell lines. Furthermore, we show
      that AXL-dependent peripheral distribution of lysosomes and cell invasion are
      mediated by extracellular acidification, which is potentiated by AXL-induced
      secretion of lactate through AKT-NF-kappaB-dependent MCT-1 regulation. Our novel
      mechanistic findings support future clinical studies to evaluate the therapeutic
      potential of the AXL inhibitor R428 (BGB324) in highly invasive EAC.

PMID- 30189360
TI  - FOXF1 Induces Epithelial-Mesenchymal Transition in Colorectal Cancer Metastasis
      by Transcriptionally Activating SNAI1.
AB  - Forkhead Box F1 (FOXF1) has been recently implicated in cancer progression and
      metastasis of lung cancer and breast cancer. However, the biological functions
      and underlying mechanisms of FOXF1 in the regulation of the progression of
      colorectal cancer (CRC) are largely unknown. We showed that FOXF1 was up
      regulated in 93 paraffin-embedded archived human CRC tissue, and both high
      expression and nuclear location of FOXF1 were significantly associated with the
      aggressive characteristics and poorer survival of CRC patients. The GSEA analysis
      showed that the higher level of FOXF1 was positively associated with an
      enrichment of EMT gene signatures, and exogenous overexpression of FOXF1 induced
      EMT by transcriptionally activating SNAI1. Exogenous overexpression FOXF1
      functionally promoted invasion and metastasis features of CRC cells, and
      inhibition of SNAI1 attenuates the invasive phenotype and metastatic potential of
      FOXF1-overexpressing CRC cells. Furthermore, the results of the tissue chip
      showed that the expression of FOXF1 was positively correlated with SNAI1 in CRC
      tissues chip. These results suggested that FOXF1 plays a critical role in CRC
      metastasis by inducing EMT via transcriptional activation of SNAI1, highlighting
      a potential new therapeutic strategy for CRC.

PMID- 30189362
TI  - Heatwave and health impact research: A global review.
AB  - BACKGROUND: Observed increases in the frequency and intensity of heatwave events,
      together with the projected acceleration of these events worldwide, has led to a
      rapid expansion in research on the health impacts of extreme heat. OBJECTIVE: To
      examine how research on heatwaves and their health-related impact is distributed
      globally. METHODS: A systematic review was undertaken. Four online databases were
      searched for articles examining links between specific historical heatwave events
      and their impact on mortality or morbidity. The locations of these events were
      mapped at a global scale, and compared to other known characteristics that
      influence heat-related illness and death. RESULTS: When examining the location of
      heatwave and health impact research worldwide, studies were concentrated on mid
      latitude, high-income countries of low- to medium-population density. Regions
      projected to experience the most extreme heatwaves in the future were not
      represented. Furthermore, the majority of studies examined mortality as a key
      indicator of population-wide impact, rather than the more sensitive indicator of
      morbidity. CONCLUSION: While global heatwave and health impact research is
      prolific in some regions, the global population most at risk of death and illness
      from extreme heat is under-represented. Heatwave and health impact research is
      needed in regions where this impact is expected to be most severe.

PMID- 30189361
TI  - Development and Validation of Nomograms for Predicting Overall and Breast Cancer
      Specific Survival in Young Women with Breast Cancer: A Population-Based Study.
AB  - INTRODUCTION: The objective of current study was to develop and validate
      comprehensive nomograms for predicting the survival of young women with breast
      cancer. METHODS: Women aged <40 years diagnosed with invasive breast cancer
      between 1990 and 2010 were selected from the Surveillance, Epidemiology, and End
      Results database and randomly divided into training (n = 12,465) and validation
      (n = 12,424) cohorts. A competing-risks model was used to estimate the
      probability of breast cancer-specific survival (BCSS). We identified and
      integrated significant prognostic factors for overall survival (OS) and BCSS to
      construct nomograms. The performance of the nomograms was assessed with respect
      to calibration, discrimination, and risk group stratification. RESULTS: The
      entire cohort comprised 24,889 patients. The 5- and 10-year probabilities of
      breast cancer-specific mortality were 11.6% and 20.5%, respectively. Eight
      independent prognostic factors for both OS and BCSS were identified and
      integrated for the construction of the nomograms. The calibration curves showed
      optimal agreement between the predicted and observed probabilities. The C-indexes
      of the nomograms in the training cohort were higher than those of the TNM staging
      system for predicting OS (0.724 vs 0.694; P < .001) and BCSS (0.733 vs 0.702; P <
      .001). Additionally, significant differences in survival were observed in
      patients stratified into different risk groups within respective TNM categories.
      CONCLUSIONS: We developed and validated novel nomograms that can accurately
      predict OS and BCSS in young women with breast cancer. These nomograms may help
      clinicians in making decisions on an individualized basis.

PMID- 30189363
TI  - Linoleic acid derived oxylipins are elevated in kidney and liver and reduced in
      serum in rats given a high-protein diet.
AB  - High protein (HP) diets are often used as a means to reduce obesity, but their
      long-term effects remain unclear. In vitro studies suggest the involvement of a
      subset of oxylipins in the tissue response to HP diets. To examine the role of
      these bioactive lipids in vivo, normal adult male Sprague Dawley rats were
      provided isocaloric diets with LP (low protein, 8% protein by weight), NP (normal
      protein, 14%) or HP (50%) diets for 2 weeks, and targeted lipidomic analysis of
      oxylipins in kidney (cortex and medulla), liver and serum was performed by HPLC
      MS/MS. The main group of oxylipins affected by the HP diet was the oxylipins
      derived from linoleic acid (LA), many of which were elevated in kidney
      (particularly the medulla) and liver, but reduced in serum of rats provided the
      HP compared to NP or LP diets. A smaller proportion of other n-6 fatty acid
      derived oxylipins were lower in kidney and higher in liver, and none were
      affected in serum, by HP feeding. Few n-3 oxylipins were affected by protein
      level. In liver only, the oxylipin product to substrate ratios of the soluble
      epoxide hydrolase enzyme were higher in LP fed rats. Differences between cortex
      and medulla oxylipins suggest relatively higher cortex activity of 5- and 8
      lipoxygenase and cytochrome P450 hydroxylase, and higher medulla cyclooxygenase
      and 12- and 15-lipoxygenase activity. Further studies are needed to elucidate the
      physiological effects of the changes in these novel oxylipins in response to
      short-term dietary HP.

PMID- 30189364
TI  - Loss of DJ-1 promotes browning of white adipose tissue in diet-induced obese
      mice.
AB  - The seminal discovery of browning of white adipose tissue (WAT) holds great
      promise for the treatment of obesity and metabolic syndrome. DJ-1 is
      evolutionarily conserved across species, and mutations in DJ-1 have been
      identified in Parkinson's disease. Higher levels of DJ-1 are associated with
      obesity, but the underlying mechanism is less understood. Here, we report the
      previously unappreciated role of DJ-1 in white adipocyte biology in mature models
      of obesity. We used DJ-1 knockout (KO) mouse models and wild-type littermates
      maintained on a normal diet or high-fat diet as well as in vitro cell models to
      show the direct effects of DJ-1 depletion on adipocyte phenotype, thermogenic
      capacity, fat metabolism, and microenvironment profile. Global DJ-1 KO mice show
      increased sympathetic input to WAT and beta3-adrenergic receptor intracellular
      signaling, leading to a previously unrecognized compensatory mechanism through
      browning of WAT with associated characteristics, including high mitochondrial
      contents, reduced lipid accumulation, adequate vascularization and attenuated
      autophagy. DJ-1 KO mice had normal body weight, energy balance, and adiposity,
      which were associated with protective effects on healthy WAT expansion by
      hyperplasia. Our findings revealed that browning of inguinal WAT occurred in DJ-1
      KO mice that do not show increased predisposition to obesity and suggest that
      such potential mechanism may overcome the adverse metabolic consequences of
      obesity independent of an effect on body weight. Here, we provide the first
      direct evidence that targeting DJ-1 in adipocyte metabolic health may offer a
      unique therapeutic strategy for the treatment of obesity.

PMID- 30189365
TI  - Green tea polyphenols modify gut-microbiota dependent metabolisms of energy, bile
      constituents and micronutrients in female Sprague-Dawley rats.
AB  - Our recent metagenomics analysis has uncovered remarkable modifying effects of
      green tea polyphenols (GTP) on gut-microbiota community structure and energy
      conversion related gene orthologs in rats. How these genomic changes could
      further influence host health is still unclear. In this work, the alterations of
      gut-microbiota dependent metabolites were studied in the GTP-treated rats. Six
      groups of female SD rats (n=12/group) were administered drinking water containing
      0%, 0.5%, and 1.5% GTP (wt/vol). Their gut contents were collected at 3 and 6
      months and were analyzed via high performance liquid chromatography (HPLC) and
      gas chromatography (GC)-mass spectrometry (MS). GC-MS based metabolomics analysis
      captured 2668 feature, and 57 metabolites were imputatively from top 200
      differential features identified via NIST fragmentation database. A group of key
      metabolites were quantitated using standard calibration methods. Compared with
      control, the elevated components in the GTP-treated groups include niacin (8.61
      fold), 3-phenyllactic acid (2.20-fold), galactose (3.13-fold), mannose (2.05
      fold), pentadecanoic acid (2.15-fold), lactic acid (2.70-fold), and proline (2.15
      fold); the reduced components include cholesterol (0.29-fold), cholic acid (0.62
      fold), deoxycholic acid (0.41-fold), trehalose (0.14-fold), glucose (0.46-fold),
      fructose (0.12-fold), and alanine (0.61-fold). These results were in line with
      the genomic alterations of gut-microbiome previously discovered by metagenomics
      analysis. The alterations of these metabolites suggested the reduction of
      calorific carbohydrates, elevation of vitamin production, decreases of bile
      constituents, and modified metabolic pattern of amino acids in the GTP-treated
      animals. Changes in gut-microbiota associated metabolism may be a major
      contributor to the anti-obesity function of GTP.

PMID- 30189366
TI  - Effects of dietary omega-3 PUFAs on growth and development: Somatic,
      neurobiological and reproductive functions in a murine model.
AB  - Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) are relevant to fetal and
      infant growth and development. Objective: to assess whether long-term exposure to
      dietary omega-3 PUFA imbalance alters pre- and/or postnatal pups' development and
      reproductive function later in life. Mice dams were fed with omega-3 PUFA Control
      (soybean oil, 7%), Deficient (sunflower oil, 7%) or Excess (blend oil; 4.2% cod
      liver+2.8% soybean) diet before conception and throughout gestation-lactation and
      later on, their pups received the same diet from weaning to adulthood. Offspring
      somatic, neurobiological and reproductive parameters were evaluated. Excess pups
      were lighter during the preweaning period and shorter in length from postnatal
      day (PND) 7 to 49, compared to Control pups (P<.05). On PND14, the percentage of
      pups with eye opening in Excess group was lower than those from Control and
      Deficient groups (P<.05). In Excess female offspring, puberty onset (vaginal
      opening and first estrus) occurred significantly later and the percentage of
      parthenogenetic oocytes on PND63 was higher than Control and Deficient ones
      (P<.05). Deficient pups were shorter in length (males: on PND14, 21, 35 and 49;
      females: on PND14, 21 and 42) compared with Control pups (P<.05). Deficient
      offspring exhibited higher percentage of bending spermatozoa compared to Control
      and Excess offspring (P<.05). These results show that either an excessively high
      or insufficient omega-3 PUFA consumption prior to conception until adulthood
      seems inadvisable because of the potential risks of short-term adverse effects on
      growth and development of the progeny or long-lasting effects on their
      reproductive maturation and function.

PMID- 30189367
TI  - Alterations and structural resilience of the gut microbiota under dietary fat
      perturbations.
AB  - Disequilibrium of the gut microbiota by dietary fat has been implicated in the
      incidence of overweight or obesity. However, it remains to be elucidated whether
      dietary fat perturbations in early life have long-lasting impacts on the gut
      microbiota and to what extent unbalanced diet-induced alterations in childhood
      are reversible. Accordingly, three groups of 1-day-old hens were used. They were
      fed with a low-fat diet (LFD), basal diet (BD) and high-fat diet (HFD),
      respectively, for 6 weeks and then switched to the same normal diets (NDs) for
      another 19 weeks. At week 6, hens in the LFD and HFD groups were found to have
      higher body weight, plasma glucose, total cholesterol, triglycerides and low
      density lipoprotein cholesterol levels than their counterparts in the BD group,
      whereas upon switching to NDs, the metabolic deteriorations observed during the
      LFD consumption were alleviated. Principal component analysis revealed a shift of
      the gut microbiota structure in the LFD and HFD groups away from that of the BD
      group at week 6, while the gut microbiota structure of the LFD group was moved
      back to that of the BD group after reverting to NDs. Additionally, abnormal
      alterations of obesity-related phylotypes were observed in the LFD and HFD
      groups, whereas the abundance of these phylotypes in the LFD group was almost
      reverted to the BD levels over time. Collectively, dietary fat perturbations in
      early life have long-term impacts on hosts, and the structural resilience of the
      gut microbiota in hens fed with HFD was lower than that in their LFD
      counterparts.

PMID- 30189368
TI  - Changes in composition and lead speciation due to water washing of air pollution
      control residue from municipal waste incineration.
AB  - Changes in elemental and mineralogical composition, and lead speciation, of air
      pollution control residue (APCR) from municipal solid waste incineration, due to
      treatment by water washing, were investigated in this work and are reported in
      the context of a review of the literature. Water washing was shown to
      substantially modify the nature of APCR by: 1) removing 23% dry mass soluble
      salts to disagglomerate particles and significantly reduce concentrations of the
      associated major elements, and increase concentrations of insoluble matrix
      elements and potential pollutants; and 2) respeciating elements to form new
      phases. X-ray absorption near edge spectroscopy (XANES) showed that the 500 mg/kg
      of Pb in raw and washed APCR were comprised mainly of Pb-glass, with some PbSO4,
      and small amounts of PbO and PbCl2. Semi-quantitative linear combination fitting
      suggests that the glass in the APCR may be unstable and release Pb under the
      alkaline pH of water washing, to reprecipitate as PbO. Chemical analysis suggests
      that some Pb may be removed by washing. Scientific understanding of the
      composition of raw and washed APCR, and particularly the speciation of
      potentially toxic metals, such as Zn and Pb, can help in developing effective
      element recovery and residue treatment, utilization or disposal strategies.

PMID- 30189369
TI  - Highly efficient fluoride extraction from simulant leachate of spent potlining
      via La-loaded chelating resin. An equilibrium study.
AB  - Spent potlining (SPL) hazardous waste is a potentially valuable source of
      fluoride, which may be recovered through chemical leaching and adsorption with a
      selective sorbent. For this purpose, the commercially available chelating resin
      Purolite(r) S950+ was loaded with lanthanum ions, to create a novel ligand
      exchange sorbent. The equilibrium fluoride uptake behaviour of the resin was
      thoroughly investigated, using NaF solution and a simulant leachate of SPL waste.
      The resin exhibited a large maximum defluoridation capacity of 187 +/- 15 mg g-1
      from NaF solution and 126 +/- 10 mg g-1 from the leachate, with solution pH being
      strongly influential to uptake performance. Isotherm and spectral data indicated
      that both chemisorption and unexpected physisorption processes were involved in
      the fluoride extraction and suggested that the major uptake mechanism differed in
      each matrix. The resin demonstrates significant potential in the recovery of
      fluoride from aqueous waste-streams.

PMID- 30189370
TI  - EEG source imaging of epileptic activity at seizure onset.
AB  - Surgical resection of the seizure onset zone (SOZ) requires that this region of
      the cortex is accurately localized. The onset of a seizure may be marked by
      transient discharges, but it also may be accompanied by oscillatory, sinusoidal
      electrographic activity, such as the EEG theta rhythm. However, because of the
      superposition of the seizure signal with other electrical signals, including
      noise artifacts and non-seizure brain activity, noninvasive Electrical Source
      Imaging (ESI) of the ictal EEG activity at seizure onset remains a challenging
      task for surgical planning. In the present study, we localize the SOZ from
      oscillatory features of the EEG at the ictal onset using 256-channel high density
      electroencephalography (HD-EEG), exact sensor positions, and individual
      electrical head models constructed from the patient's T1 magnetic resonance image
      (MRI). Epileptic activities at the seizure onset were characterized with joint
      time-frequency analysis and source estimated by standardized low resolution
      electromagnetic tomography (sLORETA) inverse method. The consistency of this
      localization was examined across multiple seizures for individual patients. For
      validation, results were compared to three clinical criteria: (1) epileptogenic
      lesions, (2) seizure onset observed in intracranial EEG, and (3) successful
      surgical outcomes. In this set of 84 seizures, the onsets of 56 seizures could be
      localized. For the lateralization measure, the results from HD-EEG with
      interictal spikes (8/10) and with ictal onset (10/10) were more accurate than
      international 10-20 EEG for interictal spikes (5/10) and ictal onset (5/10). ESI
      from HD-EEG with ictal onset (9/10) had greater concordance to the clinical
      criteria than HD-EEG with interictal spikes (6/10). Noninvasive ESI of
      oscillatory features at ictal onset using 256-channel HD-EEG and high-resolution
      individual head models can make a useful contribution to the clinical
      localization of the SOZ in presurgical planning.

PMID- 30189371
TI  - Effects of physical exhaustion on local dynamic stability and automaticity of
      walking.
AB  - BACKGROUND: While the effects of diseases, performance of proprioceptors, anxiety
      or pain on gait stability or automaticity of walking are well-explored, physical
      fatigue might be another relevant factor whose consequences are not sufficiently
      investigated, yet. RESEARCH QUESTION: The aim of the current study was to
      evaluate the effect of physical exhaustion on local dynamic stability (LDS) and
      automaticity of gait. METHODS: In a randomized controlled trial, 30 young and
      healthy adults were randomly assigned to either a passive control group or a
      fatigue group. The participants assigned to the fatigue group passed a shuttle
      run test which finished at maximal exhaustion while those of the control group
      rested in sitting position for 15 min. Immediately before and after the
      intervention, local dynamic gait stability as well as the cognitive (serial seven
      subtractions) and motor dual-task costs, as a measure of automaticity, were
      registered. RESULTS: While there was no effect of fatigue on LDS during single
      task walking, we observed an interaction effect for LDS in the dual-task
      condition (p = .034) and for the motor dual-task costs (p = .031). Lower dual
      task costs were found in the fatigued group in the post-test compared to the pre
      test while the control group increased their costs at the same time.
      SIGNIFICANCE: In conclusion, gait automaticity might increase after total
      exhaustion in young adults. Still, the underlying mechanisms are not completely
      resolved and further research incorporating measurements of cortical gait control
      might be promising.

PMID- 30189372
TI  - Association of fasting serum glucose level and type 2 diabetes with
      hepatocellular carcinoma in men with chronic hepatitis B infection: A large
      cohort study.
AB  - BACKGROUND: It is unclear whether elevated fasting serum glucose level and type 2
      diabetes (T2DM) are associated with an increased risk of hepatocellular carcinoma
      (HCC), irrespective of obesity in patients with chronic hepatitis B. PATIENTS AND
      METHODS: Our study population comprised 214,167 Korean men with chronic hepatitis
      B in the National Health Insurance Service (NHIS) database between January 2002
      and December 2006. Data on new events of HCC were obtained by records of the NHIS
      during the follow-up. We used Cox proportional hazards models adjusted for
      sociodemographic, lifestyle, health status and clinical conditions to estimate
      the hazard ratio (HR) and 95% confidence intervals (95% CIs) of HCC associated
      with different categories of fasting serum glucose level and T2DM, using fasting
      serum glucose <90 mg/dL as reference. RESULTS: During the 8 years of follow-up,
      there were 11,241 HCCs in men with chronic hepatitis B. Compared with the
      reference group, fasting serum glucose level of more than 140 mg/dL (HR = 1.46;
      95% CI: 1.36-1.57; p < 0.001) and presence of T2DM (HR = 1.23; 95% CI: 1.15-1.34;
      p < 0.001) were associated with an increased risk of HCC after controlling for
      potential confounders. Significant association with fasting serum glucose and HCC
      was found for both non-obese (<25 kg/m2) and obese (>=25.0 kg/m2) patients
      (Ptrend < 0.001). CONCLUSION: In this cohort of men with chronic hepatitis B
      infection, elevated fasting serum glucose level and T2DM were significantly
      associated with an increased risk of HCC, regardless of obesity. Glycaemic
      control in men with chronic hepatitis B patients should be considered in clinical
      practice to prevent HCC.

PMID- 30189373
TI  - Reduced testosterone and Ddx3y expression caused by long-term exposure to arsenic
      and its effect on spermatogenesis in mice.
AB  - Arsenic (As) has been recognized as a cause of male reproductive toxicity.
      However, effects of long-term arsenic exposure (puberty-adult) on
      spermatogenesis, testosterone synthesis, and the expression of androgen binding
      protein (ABP) and Ddx3y remain unclear. The objective of this investigation was
      to explore these effects and the underlying mechanisms. Male mice were treated
      with 5 and 50 ppm arsenic for 6 months via drinking water. The results showed
      that arsenic reduced sperm count and sperm motility and enhanced the abnormal
      sperm percentage. The decrease in the number of spermatogenic cells and sperm in
      seminiferous tubules and the decline in the Johnsen score were observed in both
      arsenic-treated groups, suggesting spermatogenesis disorders. Moreover, arsenic
      diminished serum testosterone, along with the reduced expression of luteinizing
      hormone receptor (LHR), steroidogenic acute regulatory protein (StAR) and 17-beta
      hydroxysteroid dehydrogenase (17beta-HSD) genes. Arsenic also down-regulated mRNA
      levels of ABP and Ddx3y in a dose-dependent manner. Meanwhile, the protein levels
      of StAR, 17beta-HSD and Ddx3y were significantly reduced in arsenic-treated
      groups. Taken together, these results suggest that the reduced testosterone
      through inhibition of the expression of multiple genes responsible for the
      biosynthesis, the damaged androgen homeostasis partially via lessening the
      expression levels of the ABP gene and the down-regulated expression of Ddx3y, may
      contribute to spermatogenesis disorders in mice exposed to arsenic.

PMID- 30189374
TI  - iTRAQ-based secretome reveals that SiO2 induces the polarization of RAW264.7
      macrophages by activation of the NOD-RIP2-NF-kappaB signaling pathway.
AB  - Silicosis is characterized by inflammation and pulmonary fibrosis due to long
      term inhalation of crystalline silica (SiO2). To clarify the role of macrophage
      polarization in the inflammatory response of silicosis, we used iTRAQ-coupled 2D
      LC-MS/MS to study the change in the secretome in RAW264.7 macrophages. We
      successfully screened 330 differentially expressed proteins, including 120
      proteins with upregulated expression and 210 proteins with down-regulated
      expression (p < 0.05). Bioinformatics analysis showed that the differentially
      expressed proteins were mainly involved in biological processes, such as
      oxidative stress, mitochondrial damage, apoptosis and acute inflammatory
      response. In particular, the expression levels of mitochondrial apoptosis-related
      proteins, such as AKT1, BAX, HSPD1, TNF, CASP8 and DAP, were increased after SiO2
      exposure. Taken together, our study indicated that SiO2 could induce macrophage
      polarization by activation of the NOD-RIP2-NF-kappaB signaling pathway in
      RAW264.7 macrophages. This may represent a potential mechanism in the development
      of silicosis.

PMID- 30189375
TI  - An LC-ESI-MS/MS method for the simultaneous determination of pronuciferine and
      roemerine in some Papaver species.
AB  - Papaver species, well known for their alkaloids, have been used for the treatment
      of several diseases, such as inflammation, diarrhea, depression, and sleep
      disorders in certain parts of Anatolia. In this study, four Papaver species (P.
      lacerum, P. syriacum, P. glaucum and P. rhoeas) were collected from different
      localities of Turkey. Methanolic extracts were prepared from the aerial parts of
      the plants. A rapid analytical method was developed for the simultaneously
      quantitative analysis of two alkaloids, pronuciferine and roemerine, using liquid
      chromatography tandem mass spectrometry. Multiple reaction monitoring in the
      positive ionization mode was used for detection. Pronuciferine and roemerine were
      analyzed on a C18 column (2.1 * 50 mm, 3 MUm) with the mobile phase run in the
      gradient mode with 0.1% formic acid in water (A) and 0.1% formic acid in
      acetonitrile at a flow rate of 0.3 mL/min. The transitions 312.1->283.1 m/z and
      280.0->249.0 m/z were used to monitor pronuciferine and roemerine, respectively.
      The assay was linear in the concentration range of 0.01 MUg/mL to 1 MUg/mL (r =
      0.996 for roemerine, r = 0.998 for pronuciferine). The validation studies
      revealed that the method was linear, sensitive, accurate, precise, selective,
      repeatable, robust, and rugged. Finally, the developed method was applied to
      quantify pronuciferine and roemerine in the selected species. The amounts of
      pronuciferine and roemerine were respectively found as 8.5 to 48 MUg/g and 4.4 to
      43,000 MUg/g.

PMID- 30189376
TI  - Development of a novel ion-pairing UPLC method with cation-exchange solid-phase
      extraction for determination of free timolol in human plasma.
AB  - A novel UPLC-UV method was developed for analysis of timolol in human plasma
      using a simple, fast, and cost effective ion-exchange SPE procedure, followed by
      separation on a C18 UPLC column with a mobile phase consisting of acetonitrile,
      phosphate buffer, and sodium 1-octane sulfonate as an ion pairing agent. The
      method was fully validated according to US-FDA guidelines, and was found to be
      sufficiently accurate and precise for analysis of timolol in human plasma for
      clinical pharmacokinetic studies. The application of ion-exchange SPE cartridges
      for purification of timolol in plasma produced excellent percent recoveries and
      good sample clean-up, while the ion-pairing separation described here allowed
      quantitation of timolol without interference from endogenous sample components.
      The method lower limit of detection was 1.7 ng/mL and the lower limit of
      quantitation was 5.0 ng/mL, allowing for analysis of therapeutic concentrations
      of timolol in plasma.

PMID- 30189377
TI  - Sustainability evaluation and implication of a large scale membrane bioreactor
      plant.
AB  - Membrane bioreactor (MBR) technology is receiving increasing attention in
      wastewater treatment and reuse. This study presents an integral sustainability
      evaluation of a full scale MBR plant. The plant is capable of achieving prominent
      technical performance in terms of high compliance rate, low variation in effluent
      quality and high removal efficiency during long term operation. It is also more
      responsive to the new local standard with rigorous limits. However, electricity
      consumption is found to be the dominant process resulting in elevated life cycle
      environmental impacts and costs, accounting for 51.6% of the costs. As such, it
      is suggested to optimize energy use in MBR unit and implement sludge treatment
      and management. The prolonged membrane life span could also contribute largely to
      reduced life cycle environmental concerns and expenses. This study is of great
      theoretical significance and applicable value in guaranteeing the performance and
      sustainability of large scale MBR schemes.

PMID- 30189378
TI  - Fractionation of spent liquor from organosolv-pretreatment using lignin
      incompatible extraction.
AB  - Spent liquor, or liquor in short, is the liquid stream resulting from organosolv
      pretreatment of lignocellulosic materials. The recovery of GVL, lignin and
      monosaccharide from the liquor is critical for producing value-added products and
      reducing operating costs. This work presents a new method, referred to as lignin
      incompatible extraction, developed for the simultaneous recovery of GVL, lignin
      and monosaccharides from liquor. This method involves neutralisation of the
      liquor with calcium carbonate followed by extraction with toluene. Through the
      lignin-incompatible extraction, 87.6% of GVL was separated from liquor, 89.4% of
      lignin was precipitated during extraction, and 93.9% of xylose remained in the
      aqueous fraction. The lignin-incompatible extraction results correlated with the
      non-dispersion force parameters of the extracting solvent. The precipitated
      lignin indicated a lower hydrogen bonding ability and recycled GVL proved to have
      the same effectiveness in organosolv pretreatment in the first two cycles of
      operation.

PMID- 30189379
TI  - Pretreatment with lower feed moisture and lower extrusion temperatures aids in
      the increase in the fermentable sugar yields from fine-milled Douglas-fir.
AB  - The impact of independent variables of extrusion on dependent variables of pre
      milled Douglas-fir forest residuals was studied to enhance the enzymatic
      hydrolysis for production of fermentable sugar without catalysts. Co-rotating
      twin screw extruder was operated with three different feedstock moisture contents
      (30, 40, and 50%) at four different barrel temperatures (25, 50, 100, and 150 
      degrees C) as a pretreatment. The specific mechanical energy input ranged from
      0.07 and 0.30 kWh/kg and had a very strong positive correlation with torque (r =
      0.96, p < 0.01), glucose (r = 0.92, p < 0.01) and xylose/mannose yields with (r =
      0.84, p < 0.01). Douglas-fir residuals extruded at lowest moisture content (30%)
      and temperature (25  degrees C) had the highest sugar yield, requiring the
      highest SME. Higher barrel temperature increased the median particle size and had
      lower glucose and xylose/mannose yields. Recrystallization and agglomeration were
      observed under higher temperature conditions.

PMID- 30189381
TI  - Expression of NY-ESO-1, MAGE-A3, PRAME and WT1 in different subgroups of breast
      cancer: An indication to immunotherapy?
AB  - OBJECTIVES: Cancer Testis Antigens are immunogenic tumor-specific proteins. We
      investigated NY-ESO-1, MAGE-A3 and PRAME, in addition to WT1 expression in
      different Breast Cancer (BC) subtypes. We then evaluated the expression rate of
      NY-ESO-1 in early Triple Negative breast cancer (TNBC), and investigated whether
      its expression would be maintained or lost in the metastatic setting to explore
      possible immunotherapy indication. MATERIALS AND METHODS: Three subgroups of BC
      patients were selected by the expression of ER, PgR and Her2. Tissue microarray
      was performed on a total of 92 Invasive BC. Sections were stained for NY-ESO-1,
      MAGE-A3, PRAME and WT1. The second cohort was composed by 26 metastatic TNBC
      patients from whom both the primary and secondary lesion tissues were available.
      Sections were stained for NY-ESO-1. RESULTS: NY-ESO-1 was the only differentially
      expressed antigen and was absent in ER+ and ER-PgR + tumors, as for an exclusive
      expression of either NY-ESO-1 or at least one hormonal receptor (HR+). NY-ESO-1
      was particularly represented in TNBC. No correlation has been found between MAGE
      A3 and PRAME expression and subtype WT1 had low expression, except in the Her2+
      group. In the second cohort, NY-ESO-1 was expressed in 12 and 24% of primary and
      metastatic lesions respectively. CONCLUSIONS: This study defines a distinction
      between HR+ and HR-tumors through NY-ESO-1 expression. TNBC subgroup has the
      highest frequency of NY-ESO-1+ cases, and it could be the candidate population
      for the development of anti-NY-ESO-1 vaccine, both in the adjuvant or metastatic
      setting, and for the selection of cases suitable for immunotherapy.

PMID- 30189380
TI  - Impact of reactor configuration on treatment performance and microbial diversity
      in treating high-strength dyeing wastewater: Anaerobic flat-sheet ceramic
      membrane bioreactor versus upflow anaerobic sludge blanket reactor.
AB  - In this study, an anaerobic flat-sheet ceramic membrane bioreactor (AnCMBR) was
      used to treat high-strength dyeing wastewater, and compared with an upflow
      anaerobic sludge blanket (UASB) reactor. The start-up phases of the AnCMBR and
      UASB reactor were accomplished within 60 d by using cultivated seed sludge. The
      results showed that the AnCMBR had better COD, TN, and TP removal rates than the
      UASB reactor. The CH4 production of the AnCMBR was higher than that of the UASB
      reactor. The AnCMBR was operated with low energy consumption due to good water
      permeability of the flat-sheet ceramic membrane. The AnCMBR and UASB reactor had
      similar CH4-producing Archaea; Methanosaeta, Methanosarcina, and
      Methanomassiliicoccus were the most abundant. The AnCMBR had a higher proportion
      of Desulfovibrio sp. and Desulfomicrobium sp., which are reported to have the
      potential to degrade reactive dyes. A large number of sulfate-reducing enzymes
      were deduced to contribute to the sulfate-reducing pathway.

PMID- 30189382
TI  - Spectroscopic and chemometric evaluation of cling films used for wrapping of
      foodstuff and illicit drugs.
AB  - Thin films of various polymers are currently used for wrapping various food
      products and illicit drugs worldwide. In thin films, polyvinyl chloride is the
      third most widely used polymer after the polyethylene and polypropylene. These
      films usually contain harmful plasticizers such as adipates, phthalates, and
      citrates along with other additives. Plasticizers adversely affect the human
      health and therefore, their migration in foodstuff must be monitored carefully.
      By considering all these facts, this study summarizes the utilities of non
      destructive ATR-FTIR spectroscopy in the identification of base polymer as well
      as plasticizers in various cling films and application of multivariate analysis
      in the identification and classification of the cling films to their respective
      groups. In the present research, a considerable transfer of plasticizers from the
      wrapping material is observed. A spectral library is developed for all 22 cling
      film samples for further comparison of the unknown sample. The obtained results
      are promising, especially for classification purposes. The multivariate method
      significantly provides 100% of cross-validation classification along with 99.13%
      discrimination. In this study, we have developed a method to compare or link a
      cling film which somebody uses and found that there is a transfer of plasticizers
      and other additives into the food and if the manufacturing company disown that
      this specific cling film does not belong to our company. In such type of cases,
      this method could link the suspected cling film to their manufacturers with
      precision and accurateness. The chronic effect of plasticizers on human health
      can also be linked to the type of cling film the accused was using consistently.

PMID- 30189383
TI  - Interaction of chlorpropamide with serum albumin: Effect on advanced glycated end
      (AGE) product fluorescence.
AB  - Carrier proteins like bovine or human serum albumin (BSA and HSA, respectively)
      are prone to glycation as compared to the other available proteins. In this
      study, reducing sugars such as l-arabinose (ara), d-(-) galactose (gal) and d-(-)
      fructose (fru) were used to create model glycated serum albumins and binding
      ability of these with well-known antidiabetic drug chlorpropamide (CPM) was
      monitored. Fluorescence quenching experiment revealed that interaction of CPM
      with native as well as glycated albumins undergoes through a ground state complex
      formation. CPM binds strongly to glycated HSA with arabinose (gHSAara) as
      compared to other glycated systems and to the native proteins. CPM interacts
      through Van der Waals and hydrogen bonding interaction to glycated BSA by d-(-)
      fructose (gBSAfru) and also with native HSA; whereas, it's interaction with BSA
      and others glycated systems like gBSAara, gBSAgal and gHSAara occurs primarily
      through hydrophobic interaction. CPM showed an enhancement in the production of
      the advanced glycated end products (AGE) in all the glycated proteins. The
      difference in the binding capability of CPM to differently glycated albumins
      could be a major model to understand the drug carrying capacity of the glycated
      serum albumins.

PMID- 30189384
TI  - Neuronal surface antibody-mediated encephalopathy as manifestation of chronic
      graft-versus-host disease after allogeneic hematopoietic stem cell
      transplantation.
AB  - Although it remained controversial for a long time, central nervous system (CNS)
      involvement of graft-versus-host disease (GVHD) is now becoming recognized as a
      real nosological entity. Previous case reports have suggested heterogeneous
      clinical presentations and it is not excluded that the whole spectrum of
      manifestations has not yet been fully described. Here, we report the case of a 58
      year-old man with chronic GVHD who developed a rapidly ingravescent
      encephalopathy. There was no evidence for CNS immune-mediated lesions on
      conventional imaging nor for cellular infiltration in the cerebrospinal fluid.
      Serum analyses revealed the presence of anti-neuronal antibodies directed against
      anti-contactin-associated protein 2 (anti-Caspr2), a protein associated with
      voltage-gated potassium neuronal channels. Functional imaging with 2-deoxy-2
      [fluorine-18] fluoro- d-glucose integrated with computed tomography (18F-FDG PET
      CT) demonstrated diffuse cortical and subcortical hypometabolism. The patient was
      treated with a combination of immunosuppressive agents (corticosteroids,
      cyclophosphamide and rituximab) and progressively recovered normal neurocognitive
      functions. Taken together, these data suggest that CNS-GVHD may manifest as a
      reversible antibody-mediated functional encephalopathy. This report suggests for
      the first time the interest of screening for anti-neuronal antibodies and
      functional imaging with brain 18F-FDG PET-CT in diagnosing this severe
      complication of allogeneic hematopoietic cell transplantation (alloHSCT).

PMID- 30189385
TI  - Expression and functional characterization of collection-K1 from Nile tilapia
      (Oreochromis niloticus) in host innate immune defense.
AB  - Collectin-K1 (CL-K1), a multifunctional Ca2+-dependent lectin, is able to bind
      carbohydrates on pathogens and inhibit infection by direct neutralization,
      agglutination, opsonization and killing, which plays an important role in innate
      immunity. In this study, a CL-K1 homolog (OnCL-K1) was identified from Nile
      tilapia (Oreochromis niloticus) and characterized at expression and agglutination
      functional levels. The open reading frame of OnCL-K1 is 720 bp of nucleotide
      sequence encoding a polypeptide of 239 amino acids. The deduced amino acid
      sequence has two characteristic structures, containing a collagen-like region and
      a carbohydrate recognition domain. Expression analysis revealed that the OnCL-K1
      was highly expressed in the liver, and widely exhibited in other tissues
      including kidney, intestine and spleen. In addition, the OnCL-K1 expression was
      significantly up-regulated in spleen and anterior kidney following challenges
      with a Gram-positive bacterial pathogen (Streptococcus agalactiae) and a Gram
      negative bacterial pathogen (Aeromonas hydrophila). The up-regulation of OnCL-K1
      expression was also demonstrated in hepatocytes and monocytes/macrophages in
      vitro stimulation with S. agalactiae and A. hydrophila. Recombinant OnCL-K1
      protein was able to agglutinate both S. agalactiae and A. hydrophila in vitro,
      and participate in the regulation of inflammatory, migration reaction and promote
      the phagocytosis by monocytes/macrophages. Taken together, the results of this
      study indicated that OnCL-K1, possessing apparent agglutination, opsonization and
      killing ability to bacterial pathogens and participating in the regulation
      mechanisms of the non-specific cellular immune, might be involved in host defense
      of innate immunity against bacterial infection in Nile tilapia.

PMID- 30189386
TI  - A facile synthesis of polydopamine/TiO2 composite films for cell sheet harvest
      application.
AB  - This study presents a convenient and versatile way to prepare functionalized
      composite polydopamine/titanium dioxide (PDA/TiO2) film on polystyrene (PS).
      First, polystyrene substrate was immersed in dopamine chloride solution, and then
      collosol containing TiO2 and water was spun on it, to produce uniform, continuous
      PDA/TiO2 composite films. The thickness of film was controllable by adjustment of
      the spin speed. It was found that the films were strongly adhered on the PS
      substrate, with peel strength and shear strength of 2.78 MPa and 37.78 MPa,
      respectively. After 20 min of ultraviolet (365 nm) illumination, over 90% of
      fibroblasts and 77% of osteoblasts detached from the PDA/TiO2 composite film.
      Additionally, the detached cells showed good viability, allowing further culture
      and applications. This preparation method could be widely applied for cell and
      cell sheet harvesting directly from PS-based culture wares.

PMID- 30189387
TI  - Interaction between the photosynthetic anoxygenic microorganism Rhodobacter
      sphaeroides and soluble gold compounds. From toxicity to gold nanoparticle
      synthesis.
AB  - Biological processes using microorganisms for nanoparticle synthesis are
      appealing as eco-friendly nanofactories. The response of the photosynthetic
      bacterium Rhodobacter sphaeroides to gold exposure and its reducing capability of
      Au(III) to produce stable gold nanoparticles (AuNPs), using metabolically active
      bacteria and quiescent biomass, is reported in this study. In the former case,
      bacterial cells were grown in presence of gold chloride at physiological pH. Gold
      exposure was found to cause a significant increase of the lag-phase duration at
      concentrations higher than 10 MUM, suggesting the involvement of a resistance
      mechanism activated by Au(III). Transmission Electron Microscopy (TEM) and
      Scanning Electron Microscopy/Energy Dispersive X-ray Spectrometry (SEM/EDS)
      analysis of bacterial cells confirmed the extracellular formation of AuNPs.
      Further studies were carried out on metabolically quiescent biomass incubated
      with gold chloride solution. The biosynthesized AuNPs were spherical in shape
      with an average size of 10 +/- 3 nm, as analysed by Transmission Electron
      Microscopy (TEM). The nanoparticles were hydrophilic and stable against
      aggregation for several months. In order to identify the functional groups
      responsible for the reduction and stabilization of nanoparticles, AuNPs were
      analysed by Attenuated Total Reflectance-Fourier Transform Infrared (ATR-FTIR)
      spectroscopy, X-ray Photoelectron Spectroscopy (XPS), X-ray Fluorescence
      Spectrometry (XRF) and X-ray Absorption Spectroscopy (XAS) measurements. The
      obtained results indicate that gold ions bind to functional groups of cell
      membrane and are subsequently reduced by reducing sugars to gold nanoparticles
      and capped by a protein/peptide coat. Gold nanoparticles demonstrated to be
      efficient homogeneous catalysts in the degradation of nitroaromatic compounds.

PMID- 30189389
TI  - The relationship between cultural capital and lifestyle health behaviours in
      young people: a systematic review.
AB  - OBJECTIVES: While the universal prevalence of unhealthy lifestyle behaviours is
      high, cultural capital as a non-material resource shaping individuals' tastes can
      provide a substantial insight into different lifestyle behaviour choices. The aim
      of the present systematic review was to examine the evidence on the association
      between the three forms of cultural capital and lifestyle health behaviours.
      STUDY DESIGN: This is a systematic literature review following the Preferred
      Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
      Quality appraisal was carried out using the Quality Assessment Tool for
      Observational Cohort and Cross-Sectional Studies (QAT-OCCSS). METHODS: The review
      included searches of 13 electronic databases with no restriction on the year of
      publication. Data were extracted using inclusion criteria and analysed using a
      narrative format. Eighteen studies were eligible for inclusion. RESULTS: The
      relationship between cultural capital and lifestyle behaviours was confirmed in
      the studies measuring institutionalised cultural capital, and mostly supported in
      the studies that measured objectified and embodied cultural capital. While
      cultural capital had a significant relationship with some lifestyle behaviours,
      it was not significantly related to others. The important methodological
      weaknesses in the literature preclude the ability to state the associations as
      unequivocal. CONCLUSION: While the association between cultural capital and
      lifestyle behaviours was supported in most of the included studies, more rigorous
      research methods are required to effectively assess the causality between
      cultural capital and lifestyle behaviours. More precise findings may lead to new
      entry points for the development of interventions to promote healthy lifestyle
      behaviours.

PMID- 30189388
TI  - Vulnerabilities and risks of HIV infection among migrants in the Thane district,
      India.
AB  - OBJECTIVES: To explore the vulnerabilities and risks of HIV infection among
      female migrants compared with male migrants in the Thane district of Maharashtra,
      India. STUDY DESIGN: This is a cross-sectional epidemiological study. METHODS:
      Data from 35,841 migrants (men 96.2% and women 3.8%) were collected using the web
      based 'Migrant Service Delivery System.' The data were then analysed in SPSS,
      version 23.0. Statistical analysis, including Chi-squared test and multivariate
      logistic regression, was used to identify factors influencing HIV infection for
      both male and female migrants. RESULTS: It was observed that 2.96% of female
      migrants had HIV infection compared with 0.77% of male migrants. We found that
      12.1% of women consumed alcohol compared with 41.9% of men, and access to bars
      was 1.5% among women and 3.5% in men. We observed an even larger difference
      between men and women in their previous history of using brothels for sex; only
      5.9% of female migrants reported previously having used brothels for sex,
      compared with 62.9% of male migrants. Approximately 12.3% of married women and
      93.6% of married men had sex with someone other than their spouse. We found that
      67.0% of married women and 73.9% of married men reported using a condom during
      their last sexual act compared with 60.9% of unmarried women and 68.1% of
      unmarried men. CONCLUSIONS: In Thane, female migrants faced higher
      vulnerabilities and risks of HIV infection than male migrants. Consequently,
      innovative strategies are required to address these particular needs of female
      migrants.

PMID- 30189390
TI  - Biouptake of a rare earth metal (Nd) by Chlamydomonas reinhardtii -
      Bioavailability of small organic complexes and role of hardness ions.
AB  - A green alga, Chlamydomonas reinhardtii, was used to verify whether a simple
      Biotic Ligand Model (BLM) could be used to predict carefully controlled short
      term biouptake for the lanthanide, Nd. In the absence of ligands or competitors,
      Nd biouptake was well described by a Michaelis-Menten equation with an affinity
      constant, KNd, of 106.8 M-1 and a maximum internalization flux of Jmax = 1.70 *
      10-14 mol cm-2 s-1. For bi-metal mixtures containing Nd and Ca, Mg, Sm or Eu, Nd
      uptake could also be well modelled by assigning experimentally determined
      affinity constants of KCa = 102.6 M-1, KMg = 103.4 M-1, KSm = 106.5 M-1 and KEu =
      106.5 M-1. The similar values of Km and Jmax for the three rare earth elements
      (REEs): Sm, Eu and Nd is consistent with them sharing a common metal uptake site.
      On the other hand, in the presence of the small organic ligands (citric or malic
      acid), neither, free or total Nd concentrations could be used to quantitatively
      predict Nd internalization fluxes. In other words, in order to predict biouptake
      by simple BLM determinations, it was necessary to consider that the Nd complexes
      were bioavailable. The data strongly suggest that risk evaluations of the REE
      will require a new paradigm and new tools for evaluating bioavailability.

PMID- 30189392
TI  - Water extract of indoor dust induces tight junction disruption in normal human
      corneal epithelial cells.
AB  - In corneal epithelium, tight junctions play a vital role in its barrier function.
      Human cornea is highly susceptible to damage by dust. Continued daily exposure to
      dust has been associated with increased risks of corneal injury. Studies
      demonstrated that water extract of dust induced cytotoxicity in human corneal
      epithelial cells (HCECs); however, its effects on corneal epithelial barrier
      function are unknown. In this study, we determined the concentrations of heavy
      metals in water extracts of dust, with office dust having higher concentrations
      of heavy metals than housedust, and Cu and Zn being highest among metals for both
      dust. Changes in barrier function and its associated mechanism after exposing
      HCECs to water extracts of dust at 48 MUg/100 MU L for 7 d were evaluated. Water
      extracts of both dust caused decrease of TEER value (39-73%), down-regulation of
      gene expression related to tight junction and mucin (0.2-0.8 fold), and loss of
      ZO-1 immunoreactivity from cellular borders, with office dust having greater
      potential than housedust to disrupt corneal epithelial barrier function. Our data
      implied the importance to reduce heavy metals in dust to reduce their adverse
      impacts on human eyes.

PMID- 30189391
TI  - Trace elements concentrations in soil, desert-adapted and non-desert plants in
      central Iran: Spatial patterns and uncertainty analysis.
AB  - The concentrations of Cd, Cr and Pb in soil samples and As, Cd, Cr and Pb in
      plant specimens were analyzed in an arid area in central Iran. Plants were
      categorized into desert-adapted (Haloxylon ammodendron, Atraphaxis spinosa and
      Artemisia persica) and non-desert species. It was found that the trace element
      (TE) accumulating potential of the desert species (Haloxylon ammodendron and
      Artemisia persica) with a mean value of 0.1 mg kg-1 for Cd was significantly
      higher than that of the majority of the non-desert species with an average of
      0.05 mg kg-1. Artemisia also had a high As accumulating capability with a mean
      level of 0.8 mg kg-1 in comparison with an average of 0.2 mg kg-1 for most of the
      other plant species. The mean values of Cr and Pb in Haloxylon ammodendron and
      Artemisia persica were 5 and 3 mg kg-1, respectively. Among the desert-adapted
      plants, Atraphaxis proved to be a species with high Cr and Pb accumulating
      potential, as well. The geoaccumulation index and the overall pollution scores
      indicated that the highest environmental risk was related to Cd. Different
      statistical analyses were used to study the spatial patterns of soil Cd and their
      connections with pollution sources. The variogram was estimated using a classical
      approach (weighted least squares) and was compared with that of the posterior
      summaries that resulted from the Bayesian technique, which lay within the 95%
      Bayesian credible quantile intervals (BIC) of posterior parameter distributions.
      The prediction of cadmium values at un-sampled locations was implemented by multi
      Gaussian kriging and sequential Gaussian simulation methods. The prediction maps
      showed that the region most contaminated by Cd was the north-eastern part of the
      study area, which was linked to mining activities, while agricultural influence
      contributed less in this respect.

PMID- 30189393
TI  - Mapping radiation distribution on ground based on the measurement using an
      unmanned aerial vehicle.
AB  - Mapping the radiation distribution on ground during a radiological emergency
      monitoring, or decontamination mission is an important task. Accurate knowledge
      of the radioactivity distribution can help radiation workers locate the
      contamination, which reduces unnecessary radiation exposure to personnel and
      perhaps to some extent also the exposure to the public. Recently, radiation
      monitoring systems based on unmanned aerial vehicles (UAV) have been widely
      studied and employed. However, development of algorithms for mapping the
      contamination from measured data obtained by the detection system mounted on an
      UAV is still lacking. In this work, we implemented an advanced statistical
      reconstruction algorithm for mapping spread and point radiation contamination.
      The algorithm significantly improves accuracy in the scope and location of
      radiation contamination.

PMID- 30189394
TI  - IL-2-induced NF-kappaB phosphorylation upregulates cation nonselective
      conductance in human cardiac fibroblasts.
AB  - PURPOSE: Studies of negative ionotropic effects of IL-2 create the basis for
      possible IL-2 impact on nonselective conductance (GNS), which potentially makes
      these effects useful in elucidation of the pathways affected by IL-2. MATERIALS
      AND METHODS: A culture of human cardiac fibroblasts (CHCFs) was used in this
      study. A voltage clamp mode of the whole-cell patch-clamp technique was
      introduced. The level of phosphorylated NF-kappaB was determined by newly
      developed semi-quantitative ELISA. RESULTS: The IL-2 (5 ng/ml) increased the
      currents during the depolarizing clamp to larger amplitudes without changing
      their time course. In the CHCFs pretreated with 50 MUmol/L 2-APB, IL-2-induced
      increase in GNS was highly prevented (p < 0.001), indicating possible STIM-ORAI
      involvement. The CHCF perfusion with IL-2 in the presence of IMD-0354 for 14-16
      min confirmed a significant GNS prevention (between 50 and 80%), indicating
      IkappaB involvement in the IL-2-induced signaling. The CHCF perfusion with IL-2
      in the presence of Chel, induced significant prevention in the GNS expression
      (between 50 and 80%) compared to IL-2 treated cells, indicating PKC involvement.
      CONCLUSIONS: IL-2 mediated GNS increase is mediated by activation of downstream
      players such as PKC, IkappaB, and NF-kappaB, which are probably further
      responsible for the upregulation of STIM-ORAI.

PMID- 30189395
TI  - The national, regional and city divide: Social media analysis of stakeholders
      views regarding biological controls. The public reaction to the carp control
      herpes virus in Australia.
AB  - Recent research and practice in environmental management suggest sentiment
      analysis of social media communication can be a useful tool in stakeholder
      analysis of environmental policy. This is certainly the case when it comes to the
      controversial use of biological controls in dealing with invasive species.
      Current numerical scored approaches of sentiment may not reveal the reasons for
      support or opposition to environmental policies in this and other areas. In this
      study, we examine how the use of more in-depth analysis based on what key
      stakeholders say about this issue in media at a national, city or regional
      geographic level. The analysis reveals quite different reasons for support and
      opposition to the biological control of carp in Australia, and that within each
      stakeholder group it is possible for individuals to hold conflicting views and
      attitudes on this issue. We find that there are concerns at the national and city
      level about the impact of the virus and mistrust of government and science and
      that the carp species may be viewed as a valuable resource. Those responding to
      regional media expressed hope that the virus may lead to the elimination of the
      carp problem, however, they were more interested in the possible impact on the
      local environment. The multi-scaled social media analysis of stakeholder views
      about the potential biological control of carp in Australia demonstrated how
      social media comments can be used to explore the nuanced and multidimensional
      nature of community attitudes and preferences.

PMID- 30189397
TI  - Nano-scale drug delivery systems for antiarrhythmic agents.
AB  - Arrhythmia means the heart is beating too fast, too slow, or with an irregular
      pattern. Due to the side effects and low bioavailability of many antiarrhythmic
      drugs, nano-encapsulation has been widely used for their targeted delivery. Lipid
      nanocapsules, nano liposomes, nano niosomes, solid lipid nanoparticles and
      polymeric nanoparticles are common nano-carriers used for this purpose. The aim
      of this article is to summarize some of nano systems used for the specific
      delivery of antiarrhythmic agents to target tissues. At first, nanotechnology and
      its applications in drug delivery are described in brief. Then, some information
      on arrhythmias and antiarrhythmic drugs are provided. Finally, the nano drug
      delivery systems are explained and examples of their applications in
      encapsulation of antiarrhythmic drugs are presented.

PMID- 30189396
TI  - 5'-Chloro-2,2'-dihydroxychalcone and related flavanoids as treatments for
      prostate cancer.
AB  - Several flavonoids and their biosynthetic precursor chalcones were designed and
      synthesized to improve the biological effects of the lead compound 2'
      hydroxyflavonone against androgen receptor (AR)-dependent transcriptional
      stimulation. Newly synthesized chalcones 19 and 26 suppressed AR-dependent
      transcription as well as DHT-dependent growth stimulation at a low micromolar
      level. These compounds were also effective against ligand-independent
      constitutively active mutant AR derived from castration-resistant PCa (CRPC).
      Compounds 19 and 26 showed broad spectrum antiproliferative activity at 5-10 MUM
      against multiple tumor cell lines including androgen-independent and taxane
      resistant prostate cancer as well as a multidrug-resistant subline. Mode of
      action studies suggested that 19 induced sub-G1 accumulation in PC-3 cells by
      disrupting the microtubule network without affecting cell cycle progression.
      Furthermore, the in vivo effectiveness of chalcone 19 was confirmed in a
      xenograft model antitumor assay. Thus, chalcone 19 has the potential to be a
      bifunctional lead for treatment of AR-dependent PCa at lower doses as well as AR
      independent PCa, including CRPC, at higher doses.

PMID- 30189398
TI  - Forward osmosis system analysis for optimum design and operating conditions.
AB  - Low energy consumption and less fouling propensity of forward osmosis (FO)
      processes have been attractive as a promising water filtration technology. The
      performance of this process is however significantly influenced by its operating
      conditions. Moreover, these operating parameters have both favourable and adverse
      effects on its performance. Therefore, it is very important to optimize its
      performance for efficient and economic operation. This study aims to develop a
      software to analyze a full-scale FO system for optimum performance. A
      comprehensive theoretical framework was developed to estimate the performance of
      FO system. Analysis results were compared with the experimental results to
      validate the models. About 5% deviation of simulation results and the
      experimental findings shows a very good agreement between them. A novel
      optimization algorithm was then developed to estimate the minimum required draw
      solution (DS) inlet flowrate and the number of elements in a pressure vessel to
      attain the design objectives (i.e. desired final DS concentration and recovery
      rate at a specific feed solution (FS) flowrate). A detailed parametric study was
      also conducted to determine the optimum operating conditions for different
      objectives. It showed that for a specific design objective, higher recovery rate
      can be achieved by increasing the DS flowrate and number of elements in a
      pressure vessel. In contrast, lower final concentration can be obtained by
      lowering the DS flowrate and increasing the number of elements. Finally, a MATLAB
      based software with graphical user interface was developed to make the analysis
      process easier and efficient.

PMID- 30189399
TI  - Comparing the performance of aerobic granular sludge versus conventional
      activated sludge for microbial log removal and effluent quality: Implications for
      water reuse.
AB  - The application of aerobic granular sludge (AGS) technology has increased in
      popularity, largely due to the smaller physical footprint, enhanced biological
      nutrient removal performance and ability to perform with a more stable operation
      when compared to conventional activated sludge (CAS) systems. To date, the
      ability of AGS to remove microbial pathogens such as; Escherichia coli, Giardia,
      and Cryptosporidium has not been reported. This study compared the log10 removal
      performance of commonly used pathogen surrogates (sulfite-reducing clostridia
      spores, f-RNA bacteriophage, E. coli and total coliforms) by AGS and CAS during
      the start-up phase, through to maturation. Results showed that AGS performed as
      well as CAS for the log10 removal performance of all microbial surrogates, except
      for spores which were removed more effectively by AGS most likely due to greater
      adherence of spores to the AGS biomass compared to CAS mixed liquor. Results
      suggest that AGS is capable of meeting or exceeding CAS-equivalent health-based
      targets for pathogen removal in the context of water recycling as well as not
      adversely affecting the secondary effluent water quality (suspended solids,
      turbidity and particle size) in terms of ultraviolet light transmissivity (254
      nm). These findings confirmed for the first time that the adoption of AGS
      operation would not adversely impact downstream tertiary disinfection processes
      from altered water quality, nor would it require further pathogen treatment
      interventions in addition to what is already required for CAS systems.

PMID- 30189400
TI  - Deciphering the degradation/chlorination mechanisms of maleic acid in the
      Fe(II)/peroxymonosulfate process: An often overlooked effect of chloride.
AB  - In recent years, a significant effort has been devoted into investigating the
      effects of chloride on the degradation kinetics of aromatic pollutants. The
      impact of chloride on the decomposition of short-chain carboxylic acid
      intermediates from aromatics degradation has often been overlooked. In this study
      the roles of chloride in the oxidation of maleic acid (MA) in the
      Fe(II)/peroxymonosulfate (PMS) process was investigated. Degradation efficiency,
      reaction intermediates, adsorbable organic halogen (AOX) accumulation and
      mineralization were examined. The chloride ion (Cl-) was found to have an overall
      negative impact on MA degradation and mineralization in the Fe(II)/PMS system.
      The presence of Cl- led to the formation of chlorinated by-products and a high
      production of AOX. The mineralization of MA was decreased with increasing Cl-
      concentrations. Kinetic modeling demonstrated the impact of various radicals
      largely depended on the concentration of Cl-. The significance of Cl2*- or Cl2
      for MA destruction was enhanced with increasing Cl- content, and overwhelmed that
      of SO4*- when the Cl- concentration was over 5 mM. In the absence of Cl-, SO4*-
      was the primary radical responsible for MA oxidation. A possible degradation
      pathway is proposed (cis-trans isomerization, decarboxylation and halogenations
      processes). These results may help to understand the full oxidation pathways of
      refractory aromatic compounds and the mechanism of chlorinated by-products
      formation in industrial saline wastewater treatment.

PMID- 30189401
TI  - Free-conditioning dewatering of sewage sludge through in situ propane hydrate
      formation.
AB  - The propane hydrate formation was proposed to have potentials in realizing free
      conditioning dewatering of sewage sludge with implications to simultaneous clean
      water extraction and highly efficient volume reduction. Primarily, the
      investigation on phase equilibrium of propane hydrates found that the organic
      components of sewage sludge promoted the propane hydrate formation in terms of
      decreasing equilibrium pressure by up to 19.2%, compared with that in pure water.
      Further, the feasibility of hydrate-based dewatering was verified through the
      observation of propane hydrate formation in sewage sludge and also the quality
      analysis of water generated from decomposition of up-floated formed hydrates. The
      formation of up-floated propane hydrates extracted water molecules from sewage
      sludge into homogeneous crystal phase, which actually excluded sludge particles
      from hydrate phase and realized the reduction of water in sludge phase. The
      efficiency of water conversion into hydrates was determined by monitoring propane
      pressure, which indicated that 14 batch runs decreased the water content of
      sludge from 98.81wt.% to 44.3wt.% under free-conditioning conditions. The
      chemical oxygen demand, total nitrogen and total phosphorus of hydrate-extracted
      water were measured to be 21 +/- 1 mg/L, 10.5 +/- 0.2 mg/L and 0.4 +/- 0 mg/L,
      respectively, which reflected the excellent separation performance and also
      indicated that the hydrate-extracted water can be directly discharged without
      further treatments. Finally, the unit energy consumption of hydrate-based
      dewatering process based on a continuous operation mode was calculated to be
      2673.96 kW h/t dry solid of sewage sludge, which was nearly half of that in
      thermal drying process. Therefore, the propane hydrate-based process is believed
      to maximize the green operation of enhanced sludge dewatering while minimizing
      the energy and additional material consumption.

PMID- 30189402
TI  - A tri-modal flocculation model coupled with TELEMAC for estuarine muds both in
      the laboratory and in the field.
AB  - Estuarine and coastal regions are often characterized by a high variability of
      suspended sediment concentrations in their waters, which influences dredging
      projects, contaminant transport, aquaculture and fisheries. Although various
      three-dimensional open source software are available to model the hydrodynamics
      of coastal water with a sediment module, the prediction of the fate and transport
      of cohesive sediments is still far from satisfied due to the lack of an efficient
      and robust flocculation model to estimate the floc settling velocity and the
      deposition rate. Single-class and sometimes two-class flocculation models are
      oversimplified and fail to examine complicated floc size distributions, while
      quadrature-based or multi-class based flocculation models may be too complicated
      to be coupled with large scale estuarine or ocean models. Therefore, a three
      class population balance model was developed to track the sizes and number
      concentrations of microflocs, macroflocs and megaflocs, respectively. With the
      assumption of a fixed size of microflocs and megaflocs, only four tracers are
      needed when coupled with the open-source TELEMAC system. It enables better
      settling flux estimates and better addresses the occurrence and concentration of
      larger megaflocs. This tri-modal flocculation model was validated with two
      experimental data sets: (1) 1-D settling column tests with the Ems mud and (2) in
      situ measurements at the WZ Buoy station on the Belgian coast. Results show that
      the flocculation properties of cohesive sediments can be reasonably simulated in
      both environments. It is also found that the number of macroflocs created, when a
      larger macrofloc breaks up, is a statistical mean value and may not be an integer
      when applying the model in the field.

PMID- 30189403
TI  - Needlescopic herniorrhaphy using one umbilical 5-mm trocar and two lateral 3-mm
      trocars: A case series.
AB  - INTRODUCTION: Laparoscopic surgery has become a standard treatment for inguinal
      hernia, with it recently being characterized by the use of smaller instruments.
      However, reports on needlescopic transabdominal preperitoneal repair using one
      umbilical 5-mm and two lateral 3-mm trocars are extremely rare. METHODS: Seven
      patients with unilateral inguinal hernia underwent this surgical procedure. A 5
      mm trocar was inserted from the umbilical and two 3-mm trocars were inserted from
      the lateral. After dissection of the preperitoneal layer, a mesh was fixed using
      a tucker inserted from the umbilical 5-mm trocar while viewing through the 3-mm
      optics from the lateral trocar. RESULTS: All procedures were completed without
      intraoperative complications and conversion to the conventional method. The
      surgical results of our needlescopic TAPP repair have been shown to not be
      inferior to those of the conventional method. CONCLUSION: Our needlescopic
      herniorrhaphy using one umbilical 5-mm trocar and two lateral 3-mm trocars is
      minimally invasive hernia repair.

PMID- 30189404
TI  - Adenoid cystic carcinoma of the breast: Experience at a tertiary care centre of
      Northern India.
AB  - INTRODUCTION: Adenoid cystic carcinoma of the breast (breast-ACC) is a rare tumor
      with a favorable prognosis, despite its triple-negative status and special type
      of basal-like tumor for which scant population-based descriptive data exist. We
      sought to provide new population-based information on breast-ACC in India. Due to
      the paucity of the number of cases, the natural history of the disease is not
      fully understood. This study was undertaken to examine the clinico-pathological
      characteristics of the disease and to evaluate the outcome of surgical
      intervention in a tertiary referral care centre. MATERIALS AND METHODS: A
      retrospective analysis of all patients diagnosed and treated for ACC Breast in
      our hospital over the past 10 years was carried out (2005-2015). A database of
      the characteristics of these patients was developed. In all, 14 patients were
      identified. The investigations performed included routine blood investigations,
      chest X-ray, bone scan and either an ultrasound or a CT scan. RESULTS: During the
      time period of 10 years, of 2347 with breast malignancy admitted to our
      department, only 14 were diagnosed as having ACC (3.15%). All patients were women
      (100%). The patients had a median age of 60.7 years (range 37-81). The most
      common symptom was lump in the breast. Two patients (14.2%) presented with nipple
      and skin retraction and two patients (14.2%) were asymptomatic with the diagnosis
      made by an incidental finding on routine examination. The CT and/or magnetic
      resonance imaging (MRI) showed the typical features of carcinoma breast. All the
      14 patients were taken up for surgery. Nine patients underwent Modified radical
      mastectomy and five patients underwent Breast conservation surgery. Axillary
      lymph node dissection was carried out in seven patients and sentinel lymph node
      biopsy in the remaining. Tumor cells had a characteristic histologic pattern of
      ACC of the breast. Perineural invasion was present in six cases. DISCUSSION: ACC
      of the breast is a very rare malignancy, accounting for less than 0.1% of all
      breast neoplasms. It affects the left and right breasts equally and tumors arise
      irrespective of the breast quadrants. However, in about 50 percent of patients,
      lesions are found in subareolar region. Pain or tenderness described in the
      minority of cases has not been correlated with histologically-confirmed
      perineural invasion. ACC is categorized as a basal-like subtype of breast
      carcinoma. Most cases are macroscopically well-circumscribed. Occasionally, pink,
      tan, or gray microcysts are evident. A tumor typically consists of a dual-cell
      population of luminal and myoepithelial-basal cells which may be arranged in one
      or more of three architectural patterns: tubular-trabecular, cribriform, and
      solid-basaloid. There is no consensus on the optimal management for patients with
      ACC of the breast. Based on its indolent clinical course and favorable outcome,
      ACC of the breast is generally cured by breast-conserving surgery, such as wide
      excision or quadrantectomy with or without radiotherapy. CONCLUSION: Breast-ACC
      among women is characterized by ER-negative/PR-negative expression, rare regional
      lymph node involvement, a favorable prognosis with excellent survival, and
      absence of associated cancers. These findings reinforce the importance of
      tailored treatments for breast-ACC and the apparent heterogeneity of basal-like
      breast cancers.

PMID- 30189405
TI  - Degradation and mechanism of 2,4-dichlorophenoxyacetic acid (2,4-D) by thermally
      activated persulfate oxidation.
AB  - The chlorinated phenoxy herbicide of 2,4-dichlorophenoxyacetic acid (2,4-D) was
      oxidized by thermally activated persulfate (TAP). This herbicide was studied for
      different persulfate dosages (0.97-7.29 g L-1), for varying initial pH levels (3
      12) and temperatures (25-70  degrees C). Compared with Fe2+/PS, TAP could achieve
      a higher total organic carbon (TOC) removal under wider pH ranges of 3-12.
      Increasing the mole ratio of PS to 2,4-D favored for the decay of 2,4-D and the
      best performance was achieved at the ratio of 50. The 2,4-D degradation rate
      constant highly depended on the initial pH and temperature, in accordance with
      the Arrhenius model, with an apparent activation energy of 135.24 kJ mol-1. The
      study of scavenging radicals and the EPR confirmed the presence of both SO4- and
      OH. However, SO4- was the predominant oxidation radical for 2,4-D decay. The
      presence of both Cl- and CO32- inhibited the degradation of 2,4-D, whereas the
      effect of NO3- could be negligible. Verified by GC/MS, HPLC and ion
      chromatography, a possible degradation mechanism was proposed.

PMID- 30189407
TI  - Phosphate helps to recover from scavenging effect of chloride in self-enhanced
      ozonation.
AB  - Self-enhanced ozonation is a new approach for generation of hydroxyl radicals at
      low pH. Unfortunately at acidic environment chloride effectively scavenges the
      radicals. Therefore, the presence of chloride in ozonated medium would be
      detrimental for the most of the process practical applications. In self-enhanced
      ozonation process almost complete degradation of aromatics is observed during
      first 10min. Addition of 3.22 mM of chloride completely hinders degradation of
      nitrobenzene (NB) or benzoic acid (BA). This work shows that the scavenging
      effect of chlorides may be overcome with an excess of phosphate. Addition of 50
      mM of phosphates to ozonated water brings back 74% removal of NB or 87% of BA,
      when 24 MUM of compound is ozonated in the presence of 3.22 mM chloride during
      60min. The excess of phosphate sufficient to overcome the scavenging activity of
      chloride in the self-enhanced ozonation of aromatic compounds at acidic pH is
      much lower than that implied by the reaction rates of both ions with hydroxyl
      radicals. To the best of our knowledge the recovering effect of phosphate has not
      been shown before.

PMID- 30189406
TI  - Distinct effect of humic acid on ferrihydrite colloid-facilitated transport of
      arsenic in saturated media at different pH.
AB  - Both humic acid and arsenic (As) have a strong affinity to ferrihydrite colloids
      (FHC). However, little is known about effects of humic acid colloid (HAC) and FHC
      interaction on transport and deposition of As in porous media. Co-transport of
      HAC-FHC and As at different pH was systematically investigated by monitoring
      their breakthrough curves (BTCs) in saturated sand columns. Colloid and solute
      transport models were used to reveal mechanisms of As transport with HAC-FHC in
      porous media. Results showed that HAC-FHC regulated As transport. Under neutral
      pH conditions, As transport was facilitated by FHC loading small chain-shaped
      HAC, while it was slightly retarded by FHC loading granular HAC. Under alkaline
      conditions, HAC was chain-shaped and coupled with FHC to facilitate As transport.
      However, mobile colloid-adsorbed As was less evident due to relatively low
      adsorption on FHC under alkaline pH in comparison with the transport under
      neutral pH. The presence of HAC occupied adsorption sites on FHC and thus
      decreased As adsorption. Arsenic adsorption on mobile FHC decreased with
      increasing HAC concentration. Therefore, HAC had an antagonistic effect on mixed
      colloid-facilitated As transport at neutral and alkaline conditions. Arsenic was
      readily co-deposited with FHC, especially at low pH. This study suggested that
      morphology and concentration of HAC, mobility of FHC, and solution pH would
      control As transport in porous media. The fate of As changed from co-transport
      with HAC-FHC to co-deposition when environmental pH decreased.

PMID- 30189408
TI  - Fate and dynamics of metal precipitates arising from acid drainage discharges to
      a river system.
AB  - Neutralisation of acid drainage creates metal-rich precipitates that may impact
      receiving water bodies. This study assessed the fate of over seven years of acid
      drainage discharges on the sediments of the lower River Murray (Australia),
      including the potential for periodic water anoxia to enhance risk via reductive
      dissolution of amorphous (Fe, Mn and co-precipitated and bound metal) oxide
      phases. With the exception of one site with restricted water exchange, elevated
      reducible/reactive metal(oid) (Fe, Ni, As, Co, Zn) concentrations were only
      observed in the localised wetland-riparian area within approximately 100 m of the
      discharges. Only a minor exceedance of national sediment quality guideline values
      occurred for Ni. In the main river channel, elevated reactive metal (Fe, Mn, Ni,
      Zn) concentrations were also only observed less than approximately 100 m from the
      drainage discharge point. This appears due to (a) rapid neutralisation of pH
      leading to metal precipitation and deposition in the localised discharge area,
      and/or (b) dilution of any metal precipitates entering the main channel with
      natural river sediments, and/or (c) flushing of precipitates downstream during
      higher flow conditions. The influence of deoxygenation on metal release was
      profound with large increases in the concentration of dissolved Fe, Mn, Zn, Ni,
      and As in the overlying water during laboratory experimental simulations.
      However, given in situ sediment metal contamination is very localised, it appears
      on a river reach scale that the acid drainage precipitates will not significantly
      contribute, over and above, the background release of these metals during these
      conditions.

PMID- 30189410
TI  - Urinary excretion studies of meldonium after multidose parenteral application.
AB  - Meldonium is a drug exhibiting cardioprotective and anti-ischemic effects. Due to
      its potential performance-enhancing benefit in sports, meldonium was added to the
      World Anti-Doping Agency list of prohibited substances in 2016. Since then, a
      high number of adverse analytical findings reported on meldonium has questioned
      meldonium's detection time in urine. Hence, the objective of the current study
      was to characterize the pharmacokinetic urinary excretion pattern of meldonium
      when administered as multiple intravenous injections. Three injections of 250 mg
      meldonium were given over a time period of five days to six healthy volunteers
      and urine samples were collected for eight months after the last injection of the
      drug. For the quantification of meldonium in urine, a liquid chromatography
      tandem mass spectrometry method was fully validated according to the World Anti
      Doping Agency guidelines in terms of specificity, matrix interferences, intra-
      and inter-day precision, accuracy, carry-over, robustness, linearity, limit of
      detection, and limit of quantification. The assay was successfully applied to the
      pharmacokinetic study. A three-compartment model was found to best describe the
      pharmacokinetics of meldonium with average alpha, beta, and gamma half-lives of
      1.4 h, 9.4 h, and 655 h, respectively. The detection time in urine varied between
      94 and 162 days.

PMID- 30189409
TI  - Cocaine toxicological findings in cases of violent death in Sao Paulo city -
      Brazil.
AB  - Violence is a dreadful phenomenon spread throughout the world, resulting in
      unfortunate events that can ultimately cause death. It is known that some
      countries play a much worrying role in this scenario than others. Brazil is one
      of them. The present work has focused on identifying the use of cocaine in 105
      postmortem cases arriving at the Institute of Legal Medicine of Sao Paulo (IML
      SP), the largest Brazilian city. Both blood and hair samples have been analyzed
      through ultra-performance liquid chromatography coupled to electrospray
      ionization tandem mass spectrometry (UPLC-ESI-MS/MS) in order to distinguish
      between recent or chronic cocaine use. The purpose of this work was to evaluate
      the proportion of cocaine use amongst violent individuals whose violence has
      ultimately led to their death. In order to do so, two previous methods, validated
      in-house, based on methanolic extraction for hair and protein precipitation for
      blood, have been used for this purpose and the final residue was analyzed through
      UPLC-ESI-MS/MS system. When looking at the demographics from the 105 postmortem
      cases analyzed, the results have shown the most critical age range to be between
      18 and 25 years old and the least frequent between 37 and 45 years old. Gender
      wise, a rather extreme difference was found as 97 of the individuals were men and
      finally, considering the manner of death, the four-category criteria established
      appear to be fairly similar with 34 cases related to general violence and risk
      behavior, 26 to drug abuse suspicion, 23 to homicide resulting from opposition to
      police intervention and 22 to possible suicide.

PMID- 30189411
TI  - Developing a rapid semi-automated sample preparation with alkaline hydrolysis in
      a 96-well plate for quantification of 11-nor-Delta9-tetrahydrocannabinol-9
      carboxylic acid in urine samples by UHPLC-MS/MS.
AB  - A simple, sensitive, rapid and robust manual (in glass tubes) and semi-automatic
      method (in a 96-well plate format) for quantification of 11-nor-Delta9
      tetrahydrocannabinol-9-carboxylic acid (THCA) in urine using a UHPLC-MS/MS have
      been developed. The methods involved hydrolysis with potassium hydroxide in a 96
      well plate, followed by neutralization and dilution of the sample in one step
      with a stable solution of formic acid-methanol-acetonitrile-water (2.2%/35/35/30)
      before centrifugation. The total chromatographic run time was 4.9 min, with
      retention times of 1.6 min for THCA. The linear calibration range (5-4000 ng/ml)
      prepared in urine matrix was wide to avoid reanalyzing. The methods take
      especially precautions to totally eliminate the carry over after run of the
      highest standard and to eliminate adsorption of THCA on lab-ware during sample
      preparation. High content of organic solvent in the neutralization and dilution
      solution and in the initial composition of the mobile phase gradient are
      therefore necessary. Standards and quality controls was pH adjusted to 8.4 to
      increase the solubility of the hydrophobic THCA in urine and prevent adsorption
      during storage. A preliminary study revealed that adsorption of THCA during semi-
      automatic sample preparation in a 96-well plate (plastic) was less compared to
      manual sample preparation in glass tube. The intermediate precision and accuracy
      by the manual and semi-automated method were less than 10% and ranged from 88% to
      114% respectively. Results from external controls from a proficiency testing
      programs were within 20% accuracy. 63 urine samples positive by immunoassay
      screening of cannabinoids were confirmed by UHPLC-MS/MS using routine manual
      preparation in glass tubes and semi-automatic sample preparation using 96-well
      plastic and glass coated plate. Percentage difference of the measurements were
      calculated and plotted according to Bland & Altman and the mean percentage
      difference was not significant.

PMID- 30189412
TI  - Respiratory syncytial virus testing capabilities and practices among National
      Respiratory and Enteric Virus Surveillance System laboratories, United States,
      2016.
AB  - BACKGROUND: Laboratory tests to detect respiratory syncytial virus (RSV) vary in
      sensitivity and specificity. Diagnostic testing practices can impact RSV disease
      diagnosis and burden estimates. OBJECTIVES: We surveyed a sample of laboratories
      that participated in the National Respiratory and Enteric Virus Surveillance
      System (NREVSS) in 2015-2016 to understand RSV testing, diagnostic capabilities,
      and practices. STUDY DESIGN: We distributed surveys in fall 2016 to NREVSS
      laboratories using an internet survey platform. We conducted a descriptive
      analysis of survey responses and stratified results by self-identified children's
      hospital laboratories (CHL, i.e. laboratories affiliated with or in a children's
      hospital) or general hospital laboratories (GHL, i.e. laboratories that performed
      analysis on specimens from only adults or adults and children). RESULTS: We
      sampled 367 (82.5%) of 445 eligible NREVSS laboratories with a 35.7% response
      rate; 11.5% (n = 15) were CHLs. All CHLs had PCR-based assay capability to test
      for RSV compared to 48.7% of GHLs (p < 0.001), and it was the most frequent
      method used by CHLs (n = 9, 75.0%). GHLs used rapid antigen detection tests most
      frequently (n = 65, 60.2%) to detect RSV compared to CHLs (p = 0.02, n = 3,
      25.0%). Almost half (n = 41, 48.2%) of GHLs reported specimen submission from
      adults >=50 years for RADTs. CONCLUSIONS: Laboratory testing and diagnostic
      capabilities differed by whether laboratories self-identified as a CHL or GHL.
      Many GHLs reported use of RADTs in adults >=50 years, a less sensitive diagnostic
      method for this population compared to PCR-based assays. RADT use in adults might
      miss RSV cases and affect diagnoses and disease burden estimates.

PMID- 30189413
TI  - Development of new HO-1 inhibitors by a thorough scaffold-hopping analysis.
AB  - HO-1 inhibition is considered a valuable anticancer approach. In fact, up
      regulation of HO-1 had been repeatedly reported in many types of human
      malignancies, and in these clinical cases, poor outcomes are reported. To
      identify novel HO-1 inhibitors suitable for drug development, a scaffold-hopping
      strategy calculation was utilized to design novel derivatives. Different parts of
      the selected molecule were analyzed and the different series of novel compounds
      were virtually evaluated. The calculation for the linker moiety of the classical
      HO-1 inhibitors structure led us to compounds 5 and 6. A synthetic pathway for
      the two molecules was designed and the compounds were synthesized. The biological
      activity revealed an HO-1 inhibition of 0.9 and 54 MUM for molecules 5 and 6
      respectively. This study suggested that our scaffold-hopping approach was
      successful and these results are ongoing for further development.

PMID- 30189414
TI  - Dihydroactinidiolide, a natural product against Abeta25-35 induced toxicity in
      Neuro2a cells: Synthesis, in silico and in vitro studies.
AB  - Synthesis of natural products has speeded up drug discovery process by minimizing
      the time for their purification from natural source. Several diseases like
      Alzheimer's disease (AD) demand exploring multi targeted drug candidates, and for
      the first time we report the multi AD target inhibitory potential of synthesized
      dihydroactinidiolide (DA). Though the activity of DA in several solvent extracts
      have been proved to possess free radical scavenging, anti bacterial and anti
      cancer activities, its neuroprotective efficacy has not been evidenced yet. Hence
      DA was successfully synthesized from beta-ionone using facile two-step oxidation
      method. It showed potent acetylcholinesterase (AChE) inhibition with half maximal
      inhibitory concentration (IC50) 34.03 nM, which was further supported by
      molecular docking results showing strong H bonding with some of the active site
      residues such as GLY117, GLY119 and SER200 of AChE. Further it displayed DPPH and
      (.NO) scavenging activity with IC50 value 50 nM and metal chelating activity with
      IC50 >270 nM. Besides, it significantly prevented amyloid beta25-35 self
      aggregation and promoted its disaggregation at 270 nM. It did not show cytotoxic
      effect towards Neuro2a (N2a) cells up to 24 h at 50 and 270 nM while it
      significantly increased viability of amyloid beta25-35 treated N2a cells through
      ROS generation at both the concentrations. Cytotoxicity profile of DA against
      human PBMC was quite impressive. Hemolysis studies also revealed very low
      hemolysis i.e. minimum 2.35 to maximum 5.61%. It also had suitable ADME
      properties which proved its druglikeness. The current findings demand for further
      in vitro and in vivo studies to develop DA as a multi target lead against AD.

PMID- 30189415
TI  - ZnO nanoparticles increase photosynthetic pigments and decrease lipid
      peroxidation in soil grown cilantro (Coriandrum sativum).
AB  - The growth of the nanotechnology industry has raised concerns about its
      environmental impacts. In particular, the effect on terrestrial plants, which are
      the primary producers of the global food chain, is widely debated. In this study,
      cilantro plants (Coriandrum sativum) were cultivated for 35 days in soil amended
      with ZnO nanoparticles (N ZnO), bulk ZnO (B ZnO) and ZnCl2 (ionic/I Zn) at 0-400
      mg/kg. Photosynthetic pigments, lipid peroxidation, 1NMR-based metabolic, and ICP
      based metallomic profiles were evaluated. All Zn compounds increased the
      chlorophyll content by at least 50%, compared to control. Only N ZnO at 400 mg/kg
      decreased lipid peroxidation by 70%. 1NMR data showed that all compounds
      significantly changed the carbinolic-based compounds, compared with control.
      Highest root and shoot uptake of Zn was observed at B 400 and I 100,
      respectively. Results of this study corroborates that N ZnO at a concentration
      <400 mg/kg improved photosynthesis pigments and the defense response in cilantro
      plants cultivated in organic soil.

PMID- 30189416
TI  - Ammonium uptake and metabolism alleviate PEG-induced water stress in rice
      seedlings.
AB  - Ammonium (NH4+) can enhance the water stress induced drought tolerance of rice
      seedlings in comparison to nitrate (NO3-) nutrition. To investigate the mechanism
      involved in nitrogen (N) uptake, N metabolism and transcript abundance of
      associated genes, a hydroponic experiment was conducted in which different N
      sources were supplied to seedlings growing under water stress. Compared to
      nitrate, ammonium prevented water stress-induced biomass, leaf SPAD and
      photosynthesis reduction to a significantly larger extent. Water stress
      significantly increased root nitrate reductase (NR) and nitrite reductase (NiR)
      activities, but decreased leaf NiR and glutamate synthetase (GS) activities under
      NO3- supply, causing lower nitrate content in roots and higher in leaves. In
      contrast, under NH4+ supply root GS and glutamine oxoglutarate aminotransferase
      (GOGAT) activities were significantly decreased under water stress, but remained
      higher in leaves, compared to NO3- treatment, which was beneficial for the
      transport and assimilation of ammonium in leaves. 15N tracing assays demonstrated
      that rice 15N uptake rate and accumulation were significant reduced under water
      stress, but were higher in plants supplied with NH4+ than with NO3-. Therefore,
      the formers showed higher leaf soluble sugar, proline and amino acids contents,
      and in turn, associated with a higher photosynthesis rate and biomass
      accumulation. Most genes related to NO3- uptake and reduction in roots and leaves
      were down-regulated; however, two ammonium transporter genes closely related to
      NH4+ uptake (AMT1;2 and AMT1;3) were up-regulated in response to water stress.
      Overall, our findings suggest that ammonium supply alleviated waters tress in
      rice seedlings, mainly by increasing root NH4+ uptake and leaf N metabolism.

PMID- 30189417
TI  - Tissue-specific and intracellular localization of indican synthase from Polygonum
      tinctorium.
AB  - The plant Polygonum tinctorium produces the secondary metabolite indican (indoxyl
      beta-D-glucoside), a precursor of the blue dye indigo. P. tinctorium synthesizes
      indican through the actions of the UDP-glucosyltransferase (UGT), indican
      synthase. Herein, we partially purified an indican synthase from the leaves and
      subsequently performed peptide mass fingerprinting analysis. Consequently, we
      identified a fragment that was homologous to a UDP-glucosyltransferase 72B
      (UGT72B) family member. We named it PtIgs (P. tinctoriumindoxyl-beta-D-glucoside
      synthase) and obtained the full-length cDNA using rapid amplification of the cDNA
      ends. The primary structure of PtIGS, which PtIgs encoded, showed high identity
      with indican synthases (ItUGT1 and ItUGT2) from Indigofera tinctoria (Inoue et
      al., 2017). Moreover, in expression analyses of P. tinctorium, PtIGS mRNA was
      virtually found only in the leaves, was most highly expressed in the 1st leaves,
      and decreased with leaf age. Because PtIGS expression tended to reflect indican
      contents and synthesis activities, we concluded that PtIGS functions as an
      indican synthase in plant cells. To examine intracellular localization of PtIGS,
      crude leaf extracts were separated into cytosol and microsome fractions, and
      found PtIGS in the cytosol and in microsome fractions. Furthermore, microsomal
      PtIGS was soluble in the presence of detergents and urea and was strongly
      associated with membranes. Finally, we confirmed endoplasmic reticulum (ER)
      membrane localization of PtIGS using ultracentrifugation with a sucrose density
      gradient. These data suggest that PtIGS interacts with some kind of proteins on
      ER membranes to certainly carry out a delivery of substrate.

PMID- 30189419
TI  - Investigating multi-leaf collimator tracking in stereotactic arrhythmic
      radioablation (STAR) treatments for atrial fibrillation.
AB  - Stereotactic arrhythmia radioablation (STAR) is an emerging treatment option for
      atrial fibrillation (AF). However, it faces possibly the most challenging motion
      compensation scenario: both respiratory and cardiac motion. Multi-leaf collimator
      (MLC) tracking is clinically used for lung cancer treatments but its capabilities
      with intracardiac targets is unknown. We report the first experimental results of
      MLC tracking for intracardiac targets. Five AF STAR plans of varying complexity
      were created. All delivered 5  *  10 Gy to both pulmonary vein antra. Three
      healthy human target motion trajectories were acquired with ultrasound and
      programmed into a motion platform. Plans were delivered with a linac to a
      dosimeter placed on the motion platform. For each motion trace, each plan was
      delivered with no MLC tracking and with MLC tracking with and without motion
      prediction. Dosimetric accuracy was assessed with gamma-tests and dose metrics.
      MLC tracking improved the dosimetric accuracy in all measurements compared to non
      tracking experiments. The average 2%/2 mm gamma-failure rate was improved from
      13.1% with no MLC tracking to 5.9% with MLC tracking (p  <  0.001) and 7.2% with
      MLC tracking and no motion prediction (p  <  0.001). MLC tracking significantly
      improved the consistency between planned and delivered target dose coverage. The
      95% target coverage with the prescription dose (V100) was improved from 60% of
      deliveries with no MLC tracking to 80% of deliveries with MLC tracking (p  = 
      0.03). MLC tracking was successfully implemented for the first time for
      intracardiac motion compensation. MLC tracking provided significant dosimetric
      accuracy improvements in AF STAR experiments, even with challenging cardiac and
      respiratory-induced target motion and complex treatment plans. These results
      warrant further investigation and optimisation of MLC tracking for intracardiac
      target motion compensation.

PMID- 30189418
TI  - Analysis of physiological traits in the response of Chenopodiaceae,
      Amaranthaceae, and Brassicaceae plants to salinity stress.
AB  - Soil salinity is one of the main factors affecting plant growth. Dissection of
      plant response to salinity into physiological traits may result a simple
      approximation than the overall response that may influence many aspects of the
      plant. In the present study two factors were considered to evaluate the
      correlation of different physiological variables in the plant response to
      salinity. The first factor was the species, with four levels (Atriplex halimus,
      Salicornia fruticosa, Cakile maritima, and Brassica rapa), and the second was the
      salinity (0, 100, 200, and 300 mM NaCl). Thus, the interrelationships of distinct
      physiological traits - leaf succulence, minerals (micronutrients and
      macronutrients), plant water relations (osmotic potential, water potential, and
      hydraulic conductivity), protein content, catalase, and unsaturated fatty acids -
      were analyzed by Discriminant Canonical Analysis (DCA). Additional information
      supplied by the interaction between the variables provided a multivariate
      response pattern in which the two factors (species x salinity) influenced the
      relationship between responses rather than affecting a single response. Such
      analysis allows to establish whether the selected trait was associated to each
      other for helping to define the best set of parameters in relation to the
      response of new genotypes to salinity. Thus, plant growth was influenced by leaf
      succulence adaptation to salt stress whereas it was not determined by water
      relations. The Na ion prevailed over K as the element with the highest
      variability in the response to salinity in A. halimus and S. fruticosa, whereas
      in C. maritima and B. rapa, Ca, S, and P stood out more. Patterns of ion
      accumulation together with the protein and unsaturated fatty acid ratios could be
      used in discriminating plant response to salt stress may be positioned in
      interrelated groups. The results highlight new evidences in the response to salt
      stress associated to a specific interrelationship of a set of physiological
      parameters.

PMID- 30189420
TI  - Understanding radionuclide production in gas target systems: the effect of
      adsorption on the target body.
AB  - Gas target systems have been used for decades on cyclotrons to produce
      radionuclides for medical imaging. However, the activity recovered from such
      targets is often lower than its theoretically predicted value. Past research has
      suggested that nuclide interactions with the walls of the target body may play a
      key role in the loss of recoverable radionuclide activity. Here, we consider gas
      targets and modify the standard radionuclide production equation by adding a loss
      term representing radionuclides depositing on the walls of the target. We derive
      the form of the deposition term based on a simple adsorption model which is then
      linearized by solving for leading order terms. The resulting production equation
      uses one fitting parameter to give an estimate of the recoverable activity
      produced in a target system, taking adsorption into account. The model is then
      fit to six data series, taken in-house and reported in the literature and a
      parity plot compares model predictions to experimental data. The model is able to
      better track the data than any previous models, and points towards a
      phenomenological understanding of adsorption in target systems.

PMID- 30189421
TI  - Radiotherapy of lung cancers: FFF beams improve dose coverage at tumor periphery
      compromised by electronic disequilibrium.
AB  - The purpose of this work was to investigate radiotherapy underdosing at the
      periphery of lung tumors, and differences in dose for treatments delivered with
      flattening filter-free (FFF) beams and with conventional flattened (FF) beams.
      The true differences between these delivery approaches, as assessed with Monte
      Carlo simulations, were compared to the apparent differences seen with clinical
      treatment planning algorithms AAA and Acuros XB. Dose was calculated in a phantom
      comprised of a chest wall, lung parenchyma, and a spherical tumor (tested
      diameters: 1, 3, and 5 cm). Three lung densities were considered: 0.26, 0.2, and
      0.1 g cm-3, representing normal lung, lung at full inspiration, and emphysematous
      lung, respectively. The dose was normalized to 50 Gy to the tumor center and
      delivered with 7 coplanar, unmodulated 6 MV FFF or FF beams. Monte Carlo
      calculations used EGSnrc and phase space files for the TrueBeam accelerator
      provided by Varian Medical Systems. Voxel sizes were 0.5 mm for the 1 cm tumor
      and 1 mm for the larger tumors. AAA and Acuros XB dose calculations were
      performed in EclipseTM with a 2.5 mm dose grid, the resolution normally used
      clinically. Monte Carlo dose distributions showed that traditional FF beams
      underdosed the periphery of the tumor by up to ~2 Gy as compared to FFF beams;
      the latter provided a more uniform dose throughout the tumor. In all cases, the
      underdosed region was a spherical shell about 5 mm thick around the tumor and
      extending into the tumor by 2-3 mm. The effect was most pronounced for smaller
      tumors and lower lung densities. The underdosing observed with conventional FF
      beams was not captured by the clinical treatment planning systems. We concluded
      that FFF beams mitigate dose loss at tumor periphery and current clinical
      practice fails to capture tumor periphery underdosing and possible ways to
      mitigate it.

PMID- 30189423
TI  - XI International Conference on Immunonutrition 2018: ISIN.

PMID- 30189422
TI  - The Effect of Overhydration on Mortality and Technique Failure Among Peritoneal
      Dialysis Patients: A Systematic Review and Meta-Analysis.
AB  - BACKGROUND: Overhydration is common among peritoneal dialysis (PD) patients and
      can affect PD-related outcomes. This paper aims to systematically investigate
      whether bioimpedance-assessed overhydration is a predictor for mortality and
      technique failure in PD patients. METHODS: We conducted a systematic review and
      meta-analysis of cohort studies on overhydration and prognosis in PD patients,
      strictly complying with the Preferred Reporting Items for Systematical Reviews
      and Meta-analyses. RESULTS: Eight articles met the selection criteria and 5
      studies were included in the meta-analysis. Meta-analyses-revealed overhydration,
      defined as a high ratio of extracellular water/total body water (ECW/TBW), was
      significantly associated with higher risk for all-cause mortality and technique
      failure. Other higher dichotomized overhydration indicators and continuous
      hydration variables all indicated overhydration as a significant risk factor for
      all-cause mortality. CONCLUSION: Overhydration, defined by a higher ratio of
      ECW/TBW, might be an independent predictor for all-cause mortality and technique
      failure among PD patients. However, more studies are needed to confirm this
      conclusion. Video Journal Club 'Cappuccino with Claudio Ronco' at
      https://www.karger.com/Journal/ArticleNews/223997?sponsor=52.

PMID- 30189425
TI  - CC Chemokine Ligand 18 Promotes Cell Proliferation and Metastasis of Urothelial
      Carcinoma via Activating PI3K/mTOR Signaling in Patient with Renal
      Transplantation.
AB  - OBJECTIVE: The study aimed to investigate the role of chemokine (C-C motif)
      ligand 18 (CCL18) in the progression of urothelial carcinoma (UC) after renal
      transplants (RT). METHODS: Tissues were collected from 60 patients with UC in
      which 24 were after RT. The tissues were all obtained from patients after radical
      cystectomy. Expression levels of CCL18 were examined by immunohistochemistry, RT
      polymerase chain -reaction (RT-PCR), and quantitative RT-PCR, respectively. WST-1
      assay was performed to determine proliferative capacity of UC cells. Migration
      and invasion of UC cells were analyzed by the using of chemotaxis and Transwell
      system. Western blotting was applied to assess the activation of PI3K-mTOR
      (Mammalian Target of Rapamycin) signaling. RESULTS: Compared to normal urothelial
      tissues, the expression levels of CCL18 were significantly increased in tumors of
      UC, and even more in tumors of UC after RT. Ectopic expression of CCL18
      efficiently enhanced the proliferation of UC cells and moreover, exacerbated the
      migration and invasion of UC cells. Furthermore, overexpressed CCL18 increased
      the phosphorylation of PI3K, Akt, and mTOR in UC cells, suggesting the
      hyperactivation of PI3K/Akt/mTOR signaling. CONCLUSIONS: The results demonstrate
      the critical role of CCL18 in the progression of UC, especially in receipt with
      RT. Our study indicates that CCL18 could serve as a biomarker and therapeutic
      target in diagnosis of recipients with UC after RT.

PMID- 30189424
TI  - Onset to Reperfusion Time Was Not Important in Mechanical Thrombectomy for
      Elderly Patients: A Retrospective Multicenter Study in Tama Area, Tokyo.
AB  - BACKGROUND: Mechanical thrombectomy (MT) has become the standard of care for
      acute ischemic stroke with large vessel occlusion; however, evidence remains
      insufficient for MT for elderly patients, especially with respect to factors
      affecting their outcomes. METHODS: This study was a retrospective analysis of a
      multicenter registry of MT, called Tama Registry of Acute Endovascular
      Thrombectomy. Patients were divided by their age into 2 groups: Nonelderly (NE; <
      80) and elderly (E; >=80). Factors related to a good outcome (modified Rankin
      scale score <=2) were examined in each group. Onset to reperfusion time (OTR) was
      stratified into 4 categories: category 1, 0 - <=180 min; category 2, > 180 -
      <=360 min; category 3, > 360 min or onset time not identified; and category 4,
      effective recanalization not achievable. RESULTS: 143 NE patients and 78 E
      patients were included in this study. The E group had less chance of achieving a
      good outcome (NE group 51%, E group 35%; p = 0.024). In the NE group, lower OTR
      category was an independent prognostic factor for good outcome (p = 0.037, OR =
      1.09). However, in the E group, OTR category was not a significant predictor on
      multivariate analysis. Instead, effective recanalization (p = 0.0081, OR 1.40)
      and lower National Institute of Health Stroke Scale score at presentation (p =
      0.0032, OR 1.02) were the independent predictors. CONCLUSIONS: In MT for elderly
      patients, effective recanalization improved the patients' outcome but OTR
      affected less. Further studies are warranted to establish the appropriate patient
      selection and treatment strategies.

PMID- 30189426
TI  - PYCARD Gene Plays a Key Role in Rapidly Progressive Glomerulonephritis: Results
      of a Weighted Gene Co-Expression Network Analysis.
AB  - BACKGROUND: Rapidly progressive glomerulonephritis (RPGN) is caused by various
      diseases process, thereby resulting in extensive crescent formation, which could
      lead to a rapid loss of kidney function. The molecular pathogenesis of RPGN
      remains largely unknown and requires clarification. The weighted gene co
      expression network analysis (WGCNA) is a powerful bioinformatics tool to identify
      meaningful molecules in diseases. METHODS: The dataset of GSE104948, which
      contains 22 RPGN and 18 normal samples, was obtained from Gene Expression Omnibus
      database. After data pre-processing, the WGCNA was performed to successfully
      cluster several significant modules. The most significant module was selected for
      further Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG)
      analysis. Visualization of network and screening of hub genes were performed by
      using Cytoscape software. RESULTS: A total of 11 modules were clustered by WGCNA,
      and the most significant module-turquoise module was selected. As discovered via
      GO enrichment and KEGG pathway analysis, the turquoise module was mainly
      associated with neutrophil activation and degranulation. After visualization and
      calculation for the network, the PYCARD gene has higher relationship score in 2
      clusters, namely, neutrophil activation and degranulation. In accordance with the
      literature review, the hub gene could be closely related to the inflammation
      response and could act as the potential therapeutic targets in RPGN. CONCLUSIONS:
      WGCNA in RPGN expression profiling was used for the first time in this paper. A
      novel hub gene closely associated with RPGN was screened out, thereby providing
      the brand-new molecular candidate for RPGN.

PMID- 30189427
TI  - Serum Calprotectin Level in Children: Marker of Obesity and its Metabolic
      Complications.
AB  - AIM: Elevated calprotectin levels have been reported in obese adults but have not
      been evaluated in pediatric population. We investigated the characteristics of
      serum calprotectin in overweight and obese children and its association with
      metabolic comorbidities. METHODS: We enrolled 131 children (11.7 +/- 4.1 years).
      According to body mass index (BMI), the subjects were divided into 3 groups:
      obese > 95th percentile; overweight BMI 75th-95th percentile, and normal weight
      BMI < 75th percentile. Patients were classified as having Metabolic Syndrome if
      they met 3 or more of the following criteria for age and sex: BMI > 97th
      percentile, triglycerides > 95th percentile, high-density lipoprotein cholesterol
      < 5th percentile, systolic and/or diastolic blood pressure > 95th percentile, and
      impaired glucose tolerance. In all patients, calprotectin serum levels were also
      detected. RESULTS: Calprotectin was higher in obese and overweight children than
      normal weight subjects (p < 0.001), with calprotectin in females being
      significantly higher than in males (p = 0.04). Increased calprotectin was related
      to pathological fasting blood glucose (p < 0.001) and insulin resistance (p =
      0.03), while BMI (p = 0.001), and diastolic pressure (p = 0.001) are independent
      factors for increased calprotectin. CONCLUSIONS: Our findings confirm the
      association between increased calprotectin and obesity also in children and
      suggest the potential utility of this biomarker in the monitoring of its
      metabolic complications.

PMID- 30189428
TI  - Meetings and Conferences.

PMID- 30189429
TI  - Benzodiazepines: A Valuable Tool in the Management of Cardiovascular Conditions.

PMID- 30189431
TI  - Fetal Skeletal Disorders.
AB  - Skeletal disorders of the fetus are quite common. The incidence is about 5:1000
      pregnancies. The disorders affect the extremities or parts of them (dysmelia),
      the whole skeleton (skeletal dysplasia), the skull (craniosynostosis) and the
      spine (dysostosis, caudal regression). About half of these diseases are complex.
      In the majority of cases the complex disorders are caused by single gene
      mutations or numeric or structural chromosomal aberrations. We explain the
      classification and diagnostic criteria for prenatal expert and screening
      ultrasound based on frequent disorders. The main diagnostic challenge concerning
      malformations of the limbs and craniosynostosis is to find out if they are
      isolated or symptoms of certain syndromes. In skeletal dysplasia it is clinically
      important to differentiate lethal entities from non-lethal.

PMID- 30189430
TI  - Markers Involved in Innate Immunity and Neutrophil Activation are Elevated during
      Acute Human Anaphylaxis: Validation of a Microarray Study.
AB  - BACKGROUND: We have previously identified the upregulation of the innate immune
      response, neutrophil activation, and apoptosis during anaphylaxis using a
      microarray approach. This study aimed to validate the differential gene
      expression and investigate protein concentrations of "hub genes" and upstream
      regulators during anaphylaxis. METHODS: Samples were collected from patients with
      anaphylaxis on their arrival at the emergency department, and after 1 and 3 h.
      mRNA levels of 11 genes (interleukin-6 [IL-6], IL-10, oncostatin M [OSM], S100A8,
      S100A9, matrix metalloproteinase 9 [MMP9], FASL, toll-like receptor 4 [TLR4],
      MYD88, triggering receptor expressed on myeloid cells 1 [TREM1], and cluster of
      differentiation 64 [CD64]) were measured in peripheral blood leucocytes using
      qPCR. Serum protein concentrations were measured by ELISA or cytometric bead
      array for 6 of these candidates. RESULTS: Of 69 anaphylaxis patients enrolled, 36
      (52%) had severe reactions, and 38 (55%) were female. Increases in both mRNA and
      protein of IL-10, S100A9, MMP9, and TREM1 were observed. OSM, S100A8, TLR4, and
      CD64 were upregulated and IL-6 protein concentrations were increased during
      anaphylaxis. Both FASL and soluble Fas ligand decreased during anaphylaxis.
      CONCLUSION: These results provide evidence for the involvement of innate immune
      pathways and myeloid cells during human anaphylaxis, validating previous
      microarray findings. Elevated S100A8, S100A9, TLR4, and TREM1 expression, and
      increased S100A9 and soluble TREM1 protein concentrations strongly suggest that
      neutrophils are activated during acute anaphylaxis.

PMID- 30189432
TI  - [Investigation of the quality of hearing aid provision in seniors considering
      cognitive functions].
AB  - In the group of people over the age of 65, hearing loss is one of the most common
      health problems. To maintain communication skills in this population, adequate
      hearing aid fitting is essential. The aim of the present study is to review the
      quality of hearing aid provision in the elderly. Furthermore, the influence of
      age and cognitive performance on speech perception should be considered. Forty
      subjects between the ages of 66 and 88 years were examined with unilateral or
      bilateral hearing aids. Average hearing loss (frequencies 0.5-1-2-4 kHz),
      averaged high-frequency hearing loss (frequencies 2-4-6 kHz), maximum
      monosyllable recognition score (German: maximales Einsilberverstehen, mEV) and
      aided speech intelligibility at 65 dB HL speech level were considered. To
      determine the potential cognitive impact on speech perception, a screening for
      dementia (DemTect test) and a working memory test were used. Although hearing
      aids showed benefit in 82% of the reviewed cases, an improvement of at least 20%
      compared with the unaided condition as required by the German
      "Hilfsmittelrichtlinie" was not achieved in 56% of the cases. Individual mEV with
      a maximum standard deviation of 10 % was not achieved in 81 % of the
      cases.Correlations between working memory performance or DemTect-test score and
      mEV were not of significance. Mild cognitive impairment and degraded working
      memory or age did not affect speech perception with hearing aids in our study
      cohort.

PMID- 30189433
TI  - Mesenteric Panniculitis (MP): A Frequent Coincidental CT Finding of Debatable
      Clinical Significance.
AB  - BACKGROUND:  Mesenteric panniculitis (MP) is histologically characterized by
      chronic nonspecific inflammation of the adipose tissue of the intestinal
      mesentery with unclear etiology. MP occurs predominantly in men, mostly in mid to
      late adulthood. MP is typically found as an incidental diagnosis on abdominal CT.
      METHODS:  A comprehensive review of the literature including case reports and
      cohort studies was performed. Therefore, a global search in PubMed was carried
      out. Search terms were (and/or) "mesenteric panniculitis", "panniculitis
      mesenterialis", "mesenteric lymph nodes", "CT", "imaging", "sclerosing
      mesenteritis", "case report", "therapy". RESULTS AND CONCLUSION:  MP is a
      relatively common CT finding. The true prevalence seems to be higher than the
      reported 0.6 % to 2.4 % due to underreporting. The most important differential
      diagnosis is malignant lymphoma, which may be difficult to distinguish from MP.
      The majority of patients with MP are clinically asymptomatic and do not require
      therapy. In rare symptomatic cases, non-specific symptoms like abdominal pain,
      fever, nausea or vomiting occur. For therapy, glucocorticoids and tamoxifen have
      been suggested. Several studies suggested that MP is associated with other
      diseases and might be a paraneoplastic phenomenon, but four recently published
      case-control studies suggest that MP is an independent non-specific benign age
      related phenomenon. However, two further studies show a possible association of
      MP with malignant lymphoma. The clinical relevance of MP remains the subject of
      scientific debate. KEY POINTS:   . Mesenteric panniculitis (MP) is a non
      specific, chronic inflammation of the mesenteric adipose tissue with
      characteristic CT signs. . MP is a relatively common incidental finding on
      abdominal CT. . Malignant lymphoma is the main differential diagnosis. . An
      association of MP with other diseases including malignancy has been discussed but
      cannot be confirmed unequivocally. . MP is rarely symptomatic with fever, nausea,
      vomiting, abdominal pain, or diarrhea. CITATION FORMAT: . Gogebakan O, Osterhoff
      MA, Albrecht T. Mesenteric Panniculitis (MP): A Frequent Coincidental CT Finding
      of Debatable Clinical Significance. Fortschr Rontgenstr 2018; 190: 1044 - 1052.

PMID- 30189434
TI  - The Influence of Implant Position on Final Clinical Outcome and Gait Analysis
      after Total Knee Arthroplasty.
AB  - The aim of the study was to evaluate the impact of implant component alignment on
      objective and subjective outcomes after total knee arthroplasty (TKA). The
      rotation of the femoral component and its influence on the final results were
      also examined. After exclusion, the study examined 102 patients (mean age, 66.28
      years; range, 51-79 years) who had undergone unilateral TKA. All of the operative
      procedures were performed by one surgeon with one type of implant. One year after
      the operation, improvements in Knee Society's Knee Scoring System, functional
      score, Western Ontario and McMaster Universities Osteoarthritis Index, and Visual
      Analog Scale were observed; however, none showed a significant correlation with
      any of the parameters analyzed by X-ray or computed tomography (CT) (alpha, beta,
      gamma, delta angles and posterior condylar angle [PCA]). Significant improvements
      were found for the vast majority of the parameters used for gate analysis at the
      final follow-up. Significant correlations were found between PCA angle and
      differences in stance phase, swing phase of the operated limb, and step width
      (all p = 0.03). No other significant relationships were found between gait
      parameters and indicators measured by X-ray and CT. None of the analyzed
      radiographic parameters, including rotation of the femoral component, correlated
      with final clinical results. Neither femoral internal rotation of 3 degrees  to 6
      degrees , nor rotation of 0 degrees  +/- 3 degrees  or 0 degrees  +/- 6 degrees 
      influenced the outcome. One year after TKA, a significant improvement was
      observed in both functional and gait parameters.

PMID- 30189435
TI  - Evaluation of Accuracy of a Three-Dimensional Printed Model in Open-Wedge High
      Tibial Osteotomy.
AB  - The purpose of this study was to evaluate the usefulness of a three-dimensional
      (3D) printed model for open-wedge high tibial osteotomy (HTO). This study
      retrospectively evaluated 20 patients with medial knee osteoarthritis and varus
      deformity. Between October 2015 and July 2016, the patients underwent open-wedge
      HTO using a 3D printed model. The mean age of patients was 55.2 years (range, 51
      60 years). The mean preoperative mechanical femorotibial angle (mFTA) was varus
      7.8 degrees (range, varus 4.7-11.6 degrees). After measuring the target angle
      using full-length lower limb weight-bearing radiography, the osteotomy was
      simulated using 3D images obtained from computed tomography (CT) with the 3D
      Slicer program. On the basis of the simulated osteotomy section and the target
      angle, the model was then designed and printed. Open-wedge HTO was then performed
      by applying the 3D printed model to the opening gap. The accuracy of osteotomy
      and the change in posterior tibial slope (PTS) angle were evaluated. The weight
      bearing line on the tibial plateau was corrected from a preoperative mean of 19.5
      +/- 9.8% to a postoperative mean of 63.1 +/- 6.1% (p < 0.001). The postoperative
      values were not statistically significantly different from the preoperative
      target points (p = 0.688). The mFTA was corrected to a postoperative mean of
      valgus 3.8 +/- 1.4 degrees. The PTS angle showed no significant change (p =
      0.256). A 3D printed model using CT may be useful for preoperative planning of
      open-wedge HTO. Satisfactory correction can be obtained without a change in the
      PTS.

PMID- 30189436
TI  - What Is the Price and Claimed Efficacy of Platelet-Rich Plasma Injections for the
      Treatment of Knee Osteoarthritis in the United States?
AB  - Platelet-rich plasma (PRP) injections are often used for the treatment of knee
      osteoarthritis (OA), despite clinical value and cost-effectiveness not being
      definitely established. PRP injections are considered as a potential means of
      reducing pain and improving function in patients with knee OA, in the hope of
      delaying or avoiding the need for surgical intervention. Centers that offer PRP
      injections usually charge patients out of pocket and directly market services.
      Therefore, the purpose of this study was to quantify the current (1) prices and
      (2) marketed clinical efficacy of autologous PRP injections for knee OA. A
      prospective cross-sectional study was performed based on 286 centers identified
      in the United States offering PRP injections for knee OA. A total of 179 (73.4%)
      centers were successfully contacted via e-mail or phone, using a simulated 52
      year-old male patient with knee OA. Scripted questions were asked by the
      simulated patient to determine the current marketed prices and clinical efficacy,
      either reported as "good results" or "symptomatic improvement," claimed by each
      treating center. The mean price for a single unilateral knee same-day PRP
      injection was $714 with a standard deviation of $144 (95% confidence interval
      [CI]: $691-737, n = 153). The mean claim of clinical efficacy was 76% with a
      standard deviation of 11% (95% CI: 73.5-78.3%, n = 84). Out of the 84 clinics, 10
      claimed "90 to 100% efficacy," 27 claimed "80 to 90%," 29 claimed "70 to 80%," 9
      claimed "60 to 70%," 8 claimed "50 to 60%," and 1 claimed "40 to 60%." These
      findings provide a unique perspective on the PRP market for the treatment of knee
      OA that is valuable to physicians and health care providers in providing better
      education to patients on the associated costs and purported clinical benefits of
      PRP injections.

PMID- 30189437
TI  - Stacked Tantalum Cones as a Method for Treating Severe Distal Femoral Bone
      Deficiency in Total Knee Arthroplasty.
AB  - Severe bone loss in distal femur has traditionally been managed with bulk
      cementing, bone graft, metal augments, trabecular metal cones, and mega
      prosthesis. The authors present an alternative method using a stacked
      configuration of two tantalum cones to manage severe distal femoral bone loss.
      This study aims to evaluate the mid-term outcomes and possible complications in
      patients treated with this novel technique. We retrospectively analyzed the
      prospectively maintained records of 16 knees (in 16 patients) presenting with
      severe distal femoral bone deficiency due to septic loosening (5), giant cell
      tumor (GCT; 4), periprosthetic fracture (3), aseptic loosening (3), and distal
      femoral comminuted fracture with severe osteoarthritis (1). A standard medial
      parapatellar approach was taken in all our cases followed by preparation of
      distal femoral bone defect and use of two bridging tantalum trabecular metal
      cones to fill the defect, followed by implantation of rotating hinge knee
      prosthesis. At an average follow-up of 57 months (4.75 years), the average Knee
      Society Score was 74.56 (64-87) and the mean range of motion was 97.8 (70-120)
      degrees. Radiologically, all 16 knees showed good osteointegration with no
      evidence of progressive radiolucency or loosening. Complications included two
      patients with superficial infection (healed with antibiotics), and one with
      recurrence of GCT requiring tumor megaprosthesis reconstruction. The authors
      concluded that the stacked configuration of cones provides additional coverage
      and stability with good osteointegration and found it to be particularly useful
      in distal femoral GCTs and fracture situations. They recommend the use of stacked
      cones in selected cases of severe distal femoral deficiency.

PMID- 30189438
TI  - Biomechanical Evaluation of Suture Anchor versus Transosseous Tunnel Patellar
      Tendon Repair Techniques.
AB  - The objective of this study is to compare the cyclic loading strength and
      ultimate failure load in suture anchor repair versus transosseous tunnel repair
      of patellar tendons using a cadaver model. Twelve cadaveric patella specimens
      were used (six matched pairs). Dual-energy X-ray absorptiometry (DXA)
      measurements were performed to ensure equal bone quality among groups. All right
      knees were assigned to the suture anchor repair group (n = 6), whereas all left
      knees were assigned to the transosseous bone tunnel group (n = 6). Suture type
      and repair configuration were equivalent. After the respective procedures were
      performed, each patella was mounted into a gripping jig. Tensile load was applied
      at a rate of 1 Hz between magnitudes of 50 and 150 N, 50 and 200 N, 50 and 250 N,
      and tensile load at a rate of 0.1 mm/s until failure. Failure was defined as a
      sharp deviation in the linear load versus displacement curve, and failure mode
      was recorded. DXA measurements demonstrated equivalence of bone quality between
      the two groups (p > 0.05). During cyclic load testing, there was only a
      statistically significant difference between the groups with regard to cyclic
      loading at the 50 to 200 N loading cycle (p = 0.010). There was no statistically
      significant difference between the groups with regard to ultimate load to failure
      (p = 0.43). Failure mode within the suture anchor cohort occurred through anchor
      pullout except for one, which failed through the tendon. All specimens within the
      transosseous cohort failed through the midsubstance of the tendon except for one,
      which failed through suture breakage. Suture anchor repair demonstrated a similar
      biomechanical profile regarding cyclic loading and ultimate load to failure when
      compared with "gold standard" transosseous tunnel patellar tendon repair with a
      trend toward less gapping in the suture anchor group. Using suture anchors for
      repair of the patella tendon has similar biomechanical properties to
      transpatellar tunnels but may provide other clinical advantages.

PMID- 30189439
TI  - Magnetic Resonance Imaging-Based Prevalence of Anterolateral Ligament
      Abnormalities and Associated Injuries in Knees with Acute Anterior Cruciate
      Ligament Injury.
AB  - The purpose of this study was to determine and compare the prevalence of
      anterolateral ligament abnormality and associated injuries among patients with
      complete and partial anterior cruciate ligament tears. In addition, the
      prevalence of associated injuries with anterolateral ligament abnormality was
      further analyzed. Of the 158 patients diagnosed with acute anterior cruciate
      ligament tear, 82 patients were diagnosed with acute complete anterior cruciate
      ligament confirmed by magnetic resonance imaging (MRI) and arthroscopic
      procedures (Group C), and 74 patients were diagnosed with acute partial anterior
      cruciate ligament tears confirmed by MRI (Group P). The status of the
      anterolateral ligament, collateral ligaments, menisci, and osseous lesions was
      assessed. There was a significantly higher prevalence of anterolateral ligament
      abnormalities in Group C than Group P (36.6 vs. 4.1%, p < 0.001). Medial
      collateral ligament, lateral collateral ligament, Segond fracture, osseous lesion
      at the fibular head, lateral tibial plateau, lateral femoral condyle, and medial
      tibial plateau were significantly associated with anterolateral ligament
      abnormality. Furthermore, severity of osseous lesion at the lateral tibial
      plateau, lateral femoral condyle, and medial tibial plateau was significantly
      associated (with linear correlation) with anterolateral ligament abnormality. The
      prevalence of anterolateral ligament abnormality was significantly higher in
      patients with complete anterior cruciate ligament tear (36.6%) than those with
      partial anterior cruciate ligament tear (4.1%), but with noticeable prevalence of
      anterolateral ligament abnormality in the partial anterior cruciate ligament tear
      group. Associated lesions significant to anterolateral ligament abnormality were
      tears in both collateral ligaments, lateral-sided osseous lesions, and osseous
      lesion of the medial tibial plateau.

PMID- 30189440
TI  - Comparing Cementing Techniques in Total Knee Arthroplasty: An In Vitro Study.
AB  - Aseptic loosening remains to be a major reason for revision in total knee
      arthroplasty. Cement penetration of 2 to 5 mm increases the interface strength
      and consequently decreases the likelihood of loosening. But despite this overall
      accepted optimal cement penetration, there is still a wide variety of cementing
      techniques used in total knee arthroplasty. The purpose of this study was to
      evaluate two cementing techniques on the tibial and femoral sides, with regard to
      cement penetration. Five paired cadaveric knees were used. A total knee
      arthroplasty was placed according to standard practice, with a setup that mimics
      the clinical practice. On the tibial side, we compared the application of cement
      to the bone surface alone, to the application of cement to both the bone surface
      and the component. On the femoral side, we compared the application of cement to
      the posterior condyles of the component and to the anterior and distal parts of
      the bone surface, to the application of cement to the component alone. After the
      cement had cured, the arthroplasty was removed and the bone was examined to
      determine the cement penetration using digital software. When applying cement to
      both the tibial bone surface and the tibial component, the cement penetration
      increased compared with applying cement to the tibial bone surface alone (3.46
      vs. 2.66 mm, p = 0.007). With regard to the distal femoral cuts, the cement
      penetration did not vary when applied to either the bone or the component (2.81
      vs. 2.91 mm). But applying it to the anterior bone surface did seem preferable,
      when compared with only applying it to the component. The average cement
      penetration did not differ, but applying the cement to the bone did enlarge the
      total length of the cement distribution (2.48 vs. 0.96 mm, p = 0.011). Almost no
      cement was detected on the posterior surface of the femoral cut. We concluded
      that applying cement to both the tibial bone surface and the component improves
      cement penetration.

PMID- 30189442
TI  - SMFM 2018 Archive: Prematurity-Part 2 (Podcast).

PMID- 30189441
TI  - Survey of Ventilation Practices in the Neonatal Intensive Care Units of the
      United States and Canada: Use of Volume-Targeted Ventilation and Barriers to Its
      Use.
AB  - OBJECTIVE:  To provide current data on ventilation practices and use of volume
      targeted ventilation (VTV) in neonatal intensive care units of the United States
      and Canada, to identify the perceived barriers to the implementation of VTV, and
      to assess the knowledge base of appropriate initial tidal volume (VT ) settings
      for different hypothetical clinical scenarios. STUDY DESIGN:  This was a cross
      sectional online survey of individual neonatologists practicing in the United
      States and Canada. RESULTS:  We received 387 responses (estimated response rate:
      ~20%). Use of VTV was much higher in Canada (81%) compared with 39% in the United
      States. In the United States, VTV use is highest in the Northwest at 77% and
      lowest in the Northeast at 32.5%. The chief barrier to use of VTV was a lack of
      knowledge about VTV and lack of appropriate equipment. The five clinical
      scenarios revealed that the majority of responders failed to select appropriate
      evidence-based VT for the specific scenario. CONCLUSION:  Pressure-controlled
      ventilation remains the predominant approach to neonatal ventilation in the
      United States, while VTV is the preferred mode in Canada. Despite available data
      and important pathophysiological differences between patients, there is
      insufficient understanding of how to choose an appropriate VT in a variety of
      common clinical scenarios among users of VTV.

PMID- 30189443
TI  - The International Guideline in Polycystic Ovary Syndrome.

PMID- 30189444
TI  - A Vision for Improving the Assessment and Management of PCOS through
      International Collaboration.

PMID- 30189445
TI  - A Summary on Polycystic Ovary Syndrome: Diagnostic Criteria, Prevalence, Clinical
      Manifestations, and Management According to the Latest International Guidelines.
AB  - Polycystic ovary syndrome (PCOS) is a common hormonal condition with
      reproductive, metabolic, and psychological sequelae. The Rotterdam Criteria are
      now internationally accepted, with different phenotypes recognized with varying
      clinical presentations and risk profiles. The complexity of the disorder, and the
      impact on quality of life, requires timely diagnosis, screening for complications
      and management strategies. PCOS remains underdiagnosed and women experience
      significant delays to diagnosis. Effective dissemination of evidence-based
      management is therefore vital. In this review, we summarize key aspects of PCOS
      as a prelude to this issue of Seminars in Reproductive Medicine on PCOS which
      focuses on the development of the international evidence-based guideline on the
      assessment and management of PCOS and the related translation program. We cover
      diagnostic criteria, prevalence, phenotypes, reproductive, metabolic, and
      psychological factors of PCOS. We also cover management strategies including
      lifestyle interventions as well as treatment of nonreproductive outcomes and
      reproductive outcomes informed by the latest international evidence-based
      guidelines.

PMID- 30189446
TI  - Application of Monash Centre for Health Research and Implementation Framework to
      the Development of Polycycstic Ovary Syndrome Guideline: A Case Study on
      Implementation.
AB  - Implementation of healthcare guidelines, a set of recommendations aiming to
      optimize patient care, can be a complex process which is at risk of poor
      translation into practice. Failure to adopt new evidence-based healthcare
      findings can contribute to a large variation in care, potentially affecting
      outcomes for service users. Designed to avoid this issue, the Monash Centre for
      Health Research and Implementation (MCHRI) knowledge translation framework was
      created to support the development and future implementation of clinical practice
      guidelines. The framework is distinguished by a focus on methodological rigor,
      stakeholder engagement, and partnership, leading to the coproduction of a
      guideline and research projects. In this article, we use the development of the
      International Evidence-based Guideline on the Assessment and Management of
      Polycystic Ovarian Syndrome (2018) as a case study to articulate the MCHRI
      knowledge translation framework. Specifically, this article discusses stakeholder
      engagement; development and codesign of evidence-based recommendations;
      implementation and knowledge generation; dissemination, translation, and scale
      up; and refinement/learning from evaluation. This case study demonstrates how
      hybrid frameworks, models, and theories for implementation, such as the MCHRI
      implementation framework, have their place in healthcare. The underlying
      principle that informs the framework is stakeholder engagement, including
      codesign, empowerment, and partnership.

PMID- 30189447
TI  - Knowledge and Practices Regarding Polycystic Ovary Syndrome among Physicians in
      Europe, North America, and Internationally: An Online Questionnaire-Based Study.
AB  - BACKGROUND: To inform knowledge translation by identifying evidence-practice gaps
      in polycystic ovary syndrome (PCOS) care and variations between disciplines and
      across world regions via an online, anonymous, devised questionnaire distributed
      via professional societies and completed by 1,495 physicians (2015-2016).
      METHODS: Multivariable logistic regression analyses generated adjusted odds
      ratios (OR) and 95% confidence intervals (CI) for associations between outcome
      measures and world region, specialty, annual patients with PCOS, age, and sex.
      RESULTS: Features corresponding to Rotterdam diagnostic criteria were well
      recognized (e.g., irregular menstrual cycles by 99% of physicians), but
      psychological implications were recognized only by 29 to 64%. Reproductive
      endocrinologists were more likely to use Rotterdam diagnostic criteria (OR: 3.1;
      95% CI: 2.3-4.3; p < 0.007) than obstetrician-gynecologists. Reproductive (OR:
      2.0; 95% CI: 1.5-2.8; p < 0.007) and medical endocrinologists (OR: 3.1; 95% CI:
      1.7-5.7; p < 0.007) were more likely to recommend lifestyle management than
      obstetrician-gynecologists. Physicians in Europe (OR: 4.7; 95% CI: 3.5-6.1; p <
      0.007) and other regions (OR: 4.0; 95% CI: 2.8-5.9; p < 0.007) were more likely
      to use Rotterdam diagnostic criteria than physicians in North America.
      CONCLUSION: Knowledge gaps in PCOS care to be addressed internationally include
      physician awareness of the breadth of PCOS features, application of diagnostic
      criteria, and recommending lifestyle management effectively.

PMID- 30189448
TI  - Large-Scale Evidence-Based Guideline Development Engaging the International PCOS
      Community.
AB  - The evidence-based guideline for the assessment and management of polycystic
      ovary syndrome (PCOS) integrates the best available evidence with international,
      multidisciplinary clinical expertise and consumer preferences to provide health
      professionals, consumers, and policy makers with high-quality, comprehensive
      guidance about diagnosing and managing PCOS. Here, we outline the rigorous and
      systematic process, defined a priori and documented to be reproducible, to
      minimize bias and maintain transparency, in alignment with the Appraisal of
      Guidelines for Research and Evaluation (AGREE II) criteria and incorporating the
      Grading of Recommendations Assessment, Development and Evaluation (GRADE)
      framework that render this PCOS evidence-based guideline credible, trustworthy,
      reliable, and useable.

PMID- 30189449
TI  - The Needs of Women and Healthcare Providers regarding Polycystic Ovary Syndrome
      Information, Resources, and Education: A Systematic Search and Narrative Review.
AB  - This article aims to identify and summarize the information, resource, and
      education needs of women with polycystic ovary syndrome (PCOS) and their
      healthcare providers. A systematic search of peer-reviewed, primary research
      literature was conducted. A total of 4,230 articles were identified, duplicates
      were removed, as well as the title and abstract of 2,819 studies and the full
      texts of 123 studies were screened against predetermined inclusion criteria.
      Findings from 35 included studies are described narratively. Main outcome
      measures include women's perceived needs for, and experiences of, PCOS care and
      information; healthcare providers' delivery of PCOS care and information; and
      healthcare providers' perceived needs for PCOS information, education programs,
      or professional development. There is a wealth of literature informing how PCOS
      information, education, and resources can better meet the needs of women, and
      about the role women expect healthcare providers to play in providing information
      within optimal PCOS care. However, few studies evaluate how well existing
      resources meet women's diverse needs. There is growing indirect evidence about
      the information and education needed by healthcare providers to provide best
      practice PCOS care. However, little research has directly investigated healthcare
      providers' information needs or efficacy of PCOS-specific educational programs
      for healthcare providers. PCOS resources for women should be comprehensive,
      evidence-based, include the bio-psychosocial dimensions of the condition, and
      available through a variety of modes. The range of healthcare providers that
      women may seek care from need resources to support consistent use of the
      recommended diagnostic criteria, effective recommendation of lifestyle
      management, and early detection and treatment of symptoms and complications.

PMID- 30189450
TI  - Evaluation of a Center of Research Excellence in Polycystic Ovary Syndrome as a
      Large-Scale Collaborative Research Translation Initiative, Including Evaluating
      Translation of Guideline Impact.
AB  - Research translation and evaluation are often underconsidered in research design
      and implementation thus limiting research benefit to the end user. In this
      article, we first describe a best practice approach to evaluation, for a center
      of research excellence in polycystic ovary syndrome. Within this, we outline a
      comprehensive research translation program with inbuilt evaluation of the first
      International Evidence-based Guideline for the Assessment and Management of
      Polycystic Ovary Syndrome (2018). We seek to provide a real-world example of
      comprehensive approaches to evaluation and research translation.

PMID- 30189451
TI  - What Can You Find about Polycystic Ovary Syndrome (PCOS) Online? Assessing Online
      Information on PCOS: Quality, Content, and User-Friendliness.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) is a common yet complex condition,
      where education is vital. It predominantly affects reproductive-aged women, the
      age group with peak use of the Internet, now a major source of health
      information. Women with PCOS are dissatisfied with care, and the lack of useful
      online information is a key concern. METHODS: Using a rigorous and systematic
      methodology, we examined the quality, information content, and user-friendliness
      of online information about PCOS. Internet searches were conducted in Australia
      and the United Kingdom in December 2015 using Google, Bing, and Yahoo with
      different browsers, operating systems, and domain names. A total of 75 Web sites
      were evaluated and categorized. RESULTS: The majority of Web sites were
      commercial (41%) and not-for-profit (76%) and were aimed at women only. Less than
      a third of the Web sites were externally accredited. Commercial Web sites and Web
      sites targeting only women had the lowest quality scores, while professional
      society Web sites and Web sites targeting only HPs scored the highest in quality.
      Accredited Web sites had higher quality and user-friendliness scores than
      nonaccredited Web sites. CONCLUSION: The majority of PCOS Web sites were
      commercially derived, targeted women, and were not accredited. There is a
      significant lack of quality, easy-to-read, evidence-based information online for
      women with PCOS.

PMID- 30189452
TI  - Ask PCOS: Identifying Need to Inform Evidence-Based App Development for
      Polycystic Ovary Syndrome.
AB  - BACKGROUND: People are increasingly seeking health information and managing their
      health through electronic technologies. We aimed to determine if women with
      polycystic ovary syndrome (PCOS) identified a need for PCOS-related mobile health
      apps and to evaluate related apps currently available. DESIGN: A national survey
      of women and a review of apps available on the iOS and Android platforms.
      SETTING: Community recruitment in Australia in 2016 and review of mobile apps
      available in 2017. SAMPLE: The survey received 264 responses. Sixteen apps
      related to PCOS were evaluated. MAIN OUTCOME MEASURES: Survey: Women's likeliness
      to use mobile health apps, specifically a PCOS-related app and preferred features
      of apps. App review: Mapping of available apps and evaluation using the Mobile
      Application Rating Scale (MARS). RESULTS: Of 264 respondents, almost all women
      had a smartphone (98%), 72% had previously used an app to manage their health,
      and most (91%) would use a PCOS-specific app if available. The most important
      feature was the availability of current, evidence-based information. Current apps
      on PCOS lack provision of quality information. CONCLUSION: Women with PCOS would
      use a PCOS-specific app of good quality that responds to their needs and
      facilitates self-care; however, currently available apps are unlikely to meet
      their information needs.

PMID- 30189453
TI  - Personalized Mobile Tool AskPCOS Delivering Evidence-Based Quality Information
      about Polycystic Ovary Syndrome.
AB  - Despite polycystic ovary syndrome (PCOS) being the most common endocrine
      condition affecting reproductive-aged women, studies have shown the information
      needs of PCOS consumers are not currently met. The expressed need by women with
      PCOS for accessible, evidence-based personalized PCOS information informed the
      design and development of the PCOS mobile tool-AskPCOS. The App provides a range
      of unique features such as: evidence-based PCOS health information, self
      diagnostic function, a question prompt list to optimize health practitioner
      engagement, and a commonly asked questions list. A five-phase App development
      process involved extensive stakeholder consultation, system architecture design,
      development of the content repository, system prototyping, and evaluation.
      AskPCOS is the first evidence-based, consumer-driven mobile App developed by
      women and for women with PCOS and utilizes innovative technology to empower PCOS
      consumers and optimize health outcomes. The App content repository is enhanced by
      the best available evidence and expertise extracted from the International
      Evidence-Based Guideline in PCOS (2018). The AskPCOS App has extensive data
      capture capability through the usage of data gathering functions and backend
      analytics to optimize responsiveness to consumer needs. In addition, the
      multilingual content and not-for-profit cost model is designed to facilitate
      worldwide adoption of the tool, and address PCOS information inequities in
      developing countries.

PMID- 30189454
TI  - A Governance Model Addressing the Challenges of Contemporary Research.
AB  - In this paper, we describe the robust governance structures and processes
      underpinning the development of the first International Evidence-Based Guideline
      for the Assessment and Management Polycystic Ovary Syndrome (2018). The guideline
      was an outcome of the Centre of Research Excellence for Polycystic Ovary
      Syndrome, and an example of a transformative, strategic research initiative to
      impact delivery model. The governance structure supported and delivered critical
      ethical and regulatory outcomes, including: broad and diverse representation
      across health professional and consumer groups and exceeded regulatory standards;
      adherence to rigorous knowledge creation processes; and compliance with the
      standards for guidelines set by the approval body, the Australian National Health
      and Medical Research Council (NHMRC). Well-articulated and appropriately
      implemented governance structures that meet the complex nature of contemporary
      research and translation activities are essential to enable distributed
      leadership and to deliver key outcomes.

PMID- 30189456
TI  - Integrated Model of Care for Polycystic Ovary Syndrome.
AB  - Polycystic ovary syndrome (PCOS) affects approximately one in seven women
      worldwide from early adulthood with heterogeneity in their healthcare needs
      through the life cycle. PCOS is challenging to diagnose and manage, with one
      third of women reporting at least a 2-year delay in diagnosis. Current clinical
      services do not satisfactorily educate and support women with their diverse
      reproductive, metabolic, and psychological care needs with fragmentation of
      services across health providers. Women are dissatisfied with the care they
      received, while the first contact general practitioners often feel ill-equipped
      to diagnose and manage PCOS. Despite national evidence-based guidelines
      recommending integrated multidisciplinary services, guideline translation has
      been limited, with wide practice variation and no optimal models of care.
      Lifestyle management and psychological support are the cornerstones of care and
      health providers who most commonly manage PCOS (general practitioners,
      dermatologists, endocrinologists, and gynecologists) require appropriate
      resources and multidisciplinary support. An evidence-based patient-centered
      clinical model of care, codeveloped by consumers and health professionals that
      provides education and resources and offers multidisciplinary holistic care, is
      vital to support women with PCOS.

PMID- 30189455
TI  - Informing Translation: The Accuracy of Information on Websites for Lifestyle
      Management of Polycystic Ovary Syndrome.
AB  - Lifestyle (diet, physical activity [PA], and/or behavioral) interventions are
      recommended for all women with polycystic ovary syndrome (PCOS) in international
      guidelines. The internet is a widely used health information resource. However,
      the accuracy of lifestyle information on PCOS websites is unknown and is reviewed
      here to inform translation of the international guideline on PCOS. An internet
      search was conducted with three search engines across different web browsers and
      countries. Accuracy was assessed through a checklist of 29 questions based on
      international guidelines for diet, PA, or weight management for the general
      population and for PCOS with higher scores indicating greater accuracy. Fifteen
      websites were eligible out of 72 (20%). The total accuracy score was 56 +/- 13
      (mean +/- standard deviation; potential range: -29 to 87) comprising 23 +/- 6 for
      diet (-11 to 33), 15 +/- 5 for PA (-9 to 27), and 14 +/- 3 for weight management
      (-8 to 24). A moderate proportion of websites provided general information on
      appropriate diet (40-80%) or weight management strategies (47-60%), but only 10
      to 40% of websites provided information on core foods, discretionary foods,
      exercise quantity/intensity, energy deficits, or behavioral strategies. Limited
      websites on PCOS contain information on lifestyle management. The majority
      provided information on general diet, PA, and weight recommendations but less
      information on practical implementation of lifestyle change as an identified
      translation gap for the international guideline on PCOS.

PMID- 30189457
TI  - Most Innovative Paper Award.
AB  - Dear Readers,It is our - and the publisher's - conviction that a scientific
      journal's mission is not only to provide its readers with the most relevant and
      interesting papers available, but also to further scientific research and to
      reward and honour those whose contributions to the advancement of science are
      truly remarkable. We are thus especially delighted to announce that from this
      year onward, we - the Editors-in-Chief together with the publisher Georg Thieme
      Verlag- will again officially award the most innovative paper published in
      Experimental and Clinical Endocrinology & Diabetes. Eligible are all original
      papers within the fields of endocrinology and diabetes published the two years
      previously, i. e. the prize awarded in 2019 will consider papers published in
      2017 and 2018.Of course, true to the title of the journal, the prize - worth ?
      4,000 - will alternate between endocrinology and diabetes and will be awarded
      either during the DGE or the DDG conference. Endocrinology will make a start in
      2019 and we are looking forward to our first winners on stage during the DGE
      conference 20-22 March 2019.

PMID- 30189458
TI  - A Pioneer in Neuroendocrinology.

PMID- 30189459
TI  - Duration of a "Brown-Like" Phenotype of White Adipose Tissue Induced by the beta3
      Agonist CL-316,243.
AB  - "Browning" i. e. the transformation of white adipose tissue into brown-like
      adipose tissue could induce efficient burning of excess fat reserves via
      induction of non-shivering thermogenesis. For example, activation of beta3
      adrenergic receptors has been show to induce such changes, however, it is still
      not clear, how long after termination of such a treatment, beneficial effects
      might be maintained. To address this question, we treated rats s.c. for 2 weeks
      with the beta3 agonist CL-316,243 at 1 mg/kg and assessed interscapular brown fat
      and inguinal white fat pads weight, UCP-1 (a marker for the brown-like fat
      phenotype) using immunohistochemistry and H&E staining, at different intervals
      after treatment termination.One 1 day after the treatment cessation there was a
      decrease of inguinal white fat pad weight and increase of interscapular fat pad.
      This change vanished at 7 days for inguinal pad and at 14 days for interscapular
      pad. Histological analysis of interscapular pads showed increased UCP-1 staining
      and brown-like morphology in H&E staining slices at 1 day, but not other time
      points. In case of inguinal pad there were brown-like features in H&E slices at 1
      day and less after 7 days, but absent at 14 days. UCP-1 staining was only
      detected 1 day after the treatment.In conclusion, the present results indicate
      that browning-like changes of white fat may be short lasting after treatment
      termination and could require maintenance treatment of inductor to achieve
      desired therapeutic effect. This might be a serious shortcoming of potential
      therapeutic use.

PMID- 30189460
TI  - The Role of Mangiferin in the Prevention of Experimentally Induced Iron Overload
      in an Animal Model.
AB  - BACKGROUND: The leaves, fruit peels, and bark of mango trees (Mangifera indica L)
      contain mangiferin as an active compound with known anti-oxidative and iron
      chelating properties. This study aims to evaluate the benefits of mangiferin in
      the management of iron overload. METHODS: Thirty rats were divided into five
      groups: normal control, rats with iron overload, and rats with iron overload
      treated with oral mangiferin doses of 50, 100, or 200 mg/kg BW, respectively. The
      iron overload in this rat model was induced by means of 15 mg intraperitoneal
      iron dextran, twice a week for 4 weeks. Plasma mangiferin was measured using high
      performance liquid chromatography, plasma ferritin by using enzyme linked
      immunosorbent assay, and iron contents of plasma, urine, and tissues by using
      atomic absorbance spectrophotometry. RESULTS: Plasma mangiferin concentration at
      doses of 50, 100, or 200 mg/kg BW were 416.10+/-112.04, 310.55+/-134.18, and
      450.11+/-165.99 ng/mL, respectively. At 50 mg/kg BW, mangiferin significantly
      decreased plasma ferritin levels (from 7051.14+/-1368.24 to 5543.80+/-1225.53
      ng/mL, (p=0.037). Mangiferin also showed tendency to increase urinary iron
      excretion and to decrease cardiac and hepatic iron accumulation. CONCLUSION: In
      our model, oral administration of mangiferin showed non-linear pharmacokinetics
      and low bioavailability. At a dose of 50 mg/kg BW, mangiferin decreased plasma
      ferritin levels significantly. Mangiferin did not prevent the increase of plasma
      iron, although it exerted tendency to increase urinary iron excretion and to
      decrease iron accumulation in liver and heart.

PMID- 30189461
TI  - Phenyl alanine & Tyrosine Amino acids Coated Magnetic Nanoparticles: Preparation
      and Toxicity study.
AB  - In this study we reported the synthesis of L-phenyl alanine (Phe) & L-tyrosine
      (Tyr) Natural Amino acids coated iron oxide magnetic nanoparticles under one-pot
      and in situ reaction. Functionalized iron oxide magnetic nanoparticles were
      characterized by X-ray diffraction (XRD), differential scanning calorimetry
      (DSC), thermogravimetric analysis (TGA), Vibrating Sample Magnetometer (VSM),
      Fourier transform infrared spectroscopy (FTIR), Scanning electron microscopy
      (SEM) and Transmission electron microscopy (TEM) techniques. Cellular toxicity of
      amino acids coated iron oxide magnetic nanoparticles was also investigated on HEK
      293 cell lines. Additionally, a hemolysis test of as prepared magnetic
      nanoparticles were performed. It was found that the synthesized Phe and Tyr
      coated magnetic nanoparticles (F@Phe NPs and F@Tyr NPs) were spherical in shape
      with an average size less than 25 nm, also the saturation magnetization (Ms) of
      the F@Phe NPs and F@Tyr NPs were about 30.02 and 58.23 emu/g, respectively, which
      was lower than those of bare Fe3O4. The TGA results show that apart from this
      weight loss, the coated sample shows a weight loss of 5.48, and 6.88%
      respectively corresponding to loss of Tyr, and Phe which is coated on the Fe3O4
      nanoparticles. At a high concentration, less than 2.92 and 3.13% hemolytic
      activity were observed for F@Phe NPs and F@Tyr NPs, respectively. The F@Phe NPs
      and F@Tyr NPs show the possibility of using this nanoparticles in the development
      of in vitro and in vivo pharmaceutical and biomedical fields due to do not
      possess a toxic effect, good zeta-potential and related small and narrow size
      distribution.

PMID- 30189463
TI  - Drug resistance mechanisms and drug susceptibility testing for tuberculosis.
AB  - Tuberculosis (TB) caused by Mycobacterium tuberculosis (MTB) is the deadliest
      infectious disease and the associated global threat has worsened with the
      emergence of drug resistance, in particular multidrug-resistant TB (MDR-TB) and
      extensively drug-resistant TB (XDR-TB). Although the World Health Organization
      (WHO) End-TB Strategy advocates for universal access to antimicrobial
      susceptibility testing, this is not widely available and/or it is still
      underused. The majority of drug resistance in clinical MTB strains is attributed
      to chromosomal mutations. Resistance-related mutations could also exert certain
      fitness cost to the drug-resistant MTB strains and growth fitness could be
      restored by the presence of compensatory mutations. Understanding these
      underlying mechanisms could provide an important insight into TB pathogenesis and
      predict the future trend of MDR-TB global pandemic. This review covers the
      mechanisms of resistance in MTB and provides a comprehensive overview of current
      phenotypic and molecular approaches for drug susceptibility testing, with
      particular attention to the methods endorsed and recommended by the WHO.

PMID- 30189462
TI  - Randomized controlled trial of a brief cognitive-behavioral strategies
      intervention for the pain, fatigue, and sleep disturbance symptom cluster in
      advanced cancer.
AB  - OBJECTIVE: Patients receiving treatment for advanced cancer suffer significant
      symptom burden, including co-occurring pain, fatigue, and sleep disturbance.
      There is limited evidence for effective interventions targeting this common
      symptom cluster. METHODS: A randomized controlled trial of a brief cognitive
      behavioral strategies (CBS) intervention was conducted. A sample of 164 patients
      with advanced cancer receiving chemotherapy practiced imagery, relaxation, and
      distraction exercises or listened to cancer education recordings (attention
      control) to manage co-occurring pain, fatigue, and sleep disturbance over a 9
      week period. Symptom cluster severity, distress, and interference with daily life
      were measured at baseline and 3, 6, and 9 weeks. We also evaluated the moderating
      influence of imaging ability and number of concurrent symptoms, and mediating
      effects of changes in stress, anxiety, outcome expectancy, and perceived control
      over symptoms. RESULTS: Compared with the cancer education condition,
      participants receiving the CBS intervention reported less symptom cluster
      distress at week 6 (M = 1.82 vs 2.15 on a 0-4 scale, P < .05). No other group
      differences were statistically significant. The number of concurrent symptoms
      moderated the intervention effect on symptom cluster interference. Changes in
      stress, outcome expectancy, and perceived control mediated the extent of
      intervention effects on symptom outcomes, primarily at weeks 6 and 9.
      CONCLUSIONS: The brief CBS intervention had limited effects in this trial.
      However, findings regarding potential mediators affirm hypothesized mechanisms
      and provide insight into ways to strengthen future interventions to reduce the
      suffering associated with co-occurring pain, fatigue, and sleep disturbance.

PMID- 30189464
TI  - Dignity-related existential distress in end-of-life cancer patients: Prevalence,
      underlying factors, and associated coping strategies.
AB  - OBJECTIVE: Cancer patients often have to face increasing levels of existential
      distress (ED) during disease progression, especially when nearing death. This
      cross-sectional study aimed to assess the prevalence of the dignity-related
      existential distress (DR-ED) in a sample of end-of-life cancer patients, and to
      explore the "existential distress" Patient Dignity Inventory (PDI-IT) subscale
      internal structure and its associations with different coping strategies.
      METHODS: Two hundred seven cancer inpatients with a Karnofsky Performance Status
      <=50 and a life expectancy of 4 months or less have been examined with the
      following self-report measures: PDI-IT, Demoralization Scale (DS-IT) and Brief
      Coping Orientation to Problem Experienced (Brief-COPE). The existential distress
      PDI-IT subscale factor structure was explored through principal component
      analysis, and the DR-ED associations with the other considered variables were
      examined through X2 tests, MANOVA, and multivariate regression analysis. RESULTS:
      Dignity-related existential distress was a problem/major problem for 18.8% of the
      patients, especially for the younger (F(1, 205) = 3.40; P = 0.020) and more
      demoralized (F(1, 205) = 20.36; P < 0.001) individuals. Factor analysis supported
      2 dimensions labeled "self-discontinuity" and "loss of personal autonomy,"
      accounting for 58% of the variance. Positive reframing (beta = -0.146, P < 0.05)
      and self-blame (beta = 0.247, P < 0.001) coping styles emerged as DR-ED
      significant predictors. CONCLUSIONS: This study showed how DR-ED is a relevant
      problem for patients nearing death and furthermore highlighted 2 underlying
      factors. Finally, the research has shown that positive reframing and self-blame
      coping styles might be clinically relevant elements for interventions on ED.

PMID- 30189465
TI  - Choosing the right mask for your Asian patient with sleep apnoea: A randomized,
      crossover trial of CPAP interfaces.
AB  - BACKGROUND AND OBJECTIVE: A major challenge with the treatment of obstructive
      sleep apnoea (OSA) is adherence to continuous positive airway pressure (CPAP)
      therapy. Mask tolerability is an important determinant of adherence, however
      evidence to guide selection of mask interfaces is lacking. METHODS: We conducted
      a randomized crossover trial of mask interfaces in CPAP therapy for moderate-to
      severe OSA to assess adherence and efficacy of CPAP therapy with nasal mask,
      nasal pillow and oronasal masks. Demographic data, Nasal Obstruction Symptom
      Evaluation (NOSE) scores and craniofacial measurements were also analysed for
      associations with adherence with oronasal masks. RESULTS: Eighty-five patients
      were included in the study (mean +/- SD age: 46 +/- 12 years; body mass index:
      29.9 +/- 5.6 kg/m2 ; apnoea-hypopnoea index (AHI): 53.6 +/- 24.0 events/h).
      Patients had better adherence with nasal masks (average night use: 3.96 +/- 2.26
      h/night) compared to oronasal masks (3.26 +/- 2.18 h/night, P < 0.001) and nasal
      pillows (3.48 +/- 2.20 h/night, P = 0.007). Residual AHI was higher with oronasal
      masks (7.2 +/- 5.2) compared to nasal masks (4.0 +/- 4.2, P < 0.001) and nasal
      pillows (4.1 +/- 3.3, P < 0.001). Twenty-two (25.9%) patients had the best
      adherence with oronasal masks (4.22 +/- 2.14 vs 2.93 +/- 2.12 h/night, P =
      0.016). These patients had lower NOSE scores (15 (0-35) vs 40 (10-55), P = 0.024)
      and larger menton-labrale inferioris/biocular width ratios (31 +/- 3% vs 28 +/-
      4%, P = 0.019). CONCLUSION: Nasal masks are the preferred interface during CPAP
      initiation. Patients with less nasal obstruction and a proportionally increased
      chin-lower lip distance to mid-face width may have better CPAP adherence with an
      oronasal mask interface.

PMID- 30189466
TI  - Insect pollination is at least as important for marketable crop yield as plant
      quality in a seed crop.
AB  - The sustainability of agriculture can be improved by integrating management of
      ecosystem services, such as insect pollination, into farming practices. However,
      large-scale adoption of ecosystem services-based practices in agriculture is
      lacking, possibly because growers undervalue the benefits of ecosystem services
      compared to those of conventional management practices. Here we show that, under
      representative real-world conditions, pollination and plant quality made similar
      contributions to marketable seed yield of hybrid leek (Allium porrum). Relative
      to the median, a 25% improvement of plant quality and pollination increased crop
      value by an estimated $18 007 and $17 174 ha-1 respectively. Across five crop
      lines, bumblebees delivered most pollination services, while other wild
      pollinator groups made less frequent but nevertheless substantial contributions.
      Honeybees actively managed for pollination services did not make significant
      contributions. Our results show that wild pollinators are an undervalued
      agricultural input and managing for enhancing pollinators makes sense
      economically in high-revenue insect-pollinated cropping systems.

PMID- 30189468
TI  - Lifestyle behaviors and psychosocial outcomes among cancer survivors.

PMID- 30189467
TI  - Chronic granulomatous skin lesions leading to a diagnosis of TAP1 deficiency
      syndrome.
AB  - Transporter associated with antigen processing (TAP) is essential for the
      stabilization and surface expression of major histocompatibility complex class I
      molecules of all nucleated cells. TAP deficiency syndrome, also known as bare
      lymphocyte syndrome type I, is a rare primary immunodeficiency disorder. We
      report a case of TAP1 deficiency revealed by skin lesions long before the
      occurrence of respiratory infectious manifestations.

PMID- 30189469
TI  - Is there more to psychosocial treatments in addiction than brief interventions?

PMID- 30189470
TI  - Attitudes and practices in the management of ADHD among healthcare professionals
      who responded to a European survey.
AB  - OBJECTIVES: To examine attitudes and practices in the management of attention
      deficit/hyperactivity disorder (ADHD) among health professionals across seven
      European countries. METHODS: The web-based survey was developed by an
      international steering committee of ADHD experts and consisted of 64 multiple
      choice questions relating to ADHD, covering the following topics: attitudes,
      diagnosis, referral, treatment and improving care. Health professionals working
      with ADHD were identified using a medical marketing database (Medical Marketing
      Service Inc., IL, USA) and invited via email to participate in the survey. No
      incentive was offered for participation and the survey was only available in
      English. RESULTS: Over 22 000 emails and postal invitations were sent. One
      hundred and thirty-four (0.6%) health professionals completed the survey. Results
      highlighted significant differences by profession and country. In general, ADHD
      is considered a clinically important and valid disorder (n = 111, 84%), with
      biological underpinnings (n = 82, 62%), continuing into adulthood (n = 123, 93%)
      and responsive to treatment. Respondents from France were less likely to be
      convinced about biological validity (n = 4, 27%) and those from Italy and France
      were more likely to be concerned about the risk of underdiagnosis (n = 9, 64% and
      n = 9, 60%, respectively). Psychologists were the specialty who most frequently
      reported not believing in the diagnostic validity of ADHD (n = 4, 19%). One-third
      (n = 25, 35%) of respondents recommended medical tests before prescribing
      medication, with differences emerging by country despite the lack of support for
      such routine assessments in the guidelines. CONCLUSIONS: Despite the very low
      response rate, intriguing country- and profession-specific differences emerged in
      this study and warrant further exploration.

PMID- 30189471
TI  - Improvement of hallucinogen persisting perception disorder (HPPD) with oral
      risperidone: case report.
AB  - We describe a 38-year-old woman who developed symptoms of hallucinogen persisting
      perception disorder (HPPD) after using lysergic acid diethylamide (LSD) once and
      continued to have symptoms of HPPD for nearly 17 years, although she did not use
      LSD after her first use. The symptoms of HPPD were temporally related to her
      first LSD use and she responded well to risperidone within a few weeks of
      commencing on the same. Although different medications have been tried in the
      management of HPPD including risperidone, olanzapine, clonidine, fluoxetine,
      sertraline, benzodiazepines and anti-epileptic medications, none have been proven
      to be the definitive medication of choice in the treatment of HPPD. Furthermore,
      there have been case reports suggesting worsening of symptoms with risperidone;
      however, the response to risperidone in our patient suggests the possibility of
      its effectiveness in the management of HPPD symptoms in some patients.

PMID- 30189472
TI  - Steps towards effective teamworking in Community Mental Health Teams.
AB  - OBJECTIVES: This paper aims to show how effective teamworking can be achieved in
      Community Mental Health Teams (CMHTs), in the context of recovery-focused care.
      METHODS: A narrative review of various governmental policy documents and selected
      papers relevant to teamworking and recovery-focused care within mental health
      services, in an Irish context. Findings Effective teamworking within CMHTs is a
      prerequisite to the provision of quality, recovery-focused care. It requires the
      management of various environmental (e.g. adopting a 'recovery' model of mental
      health), structural (e.g. sharing of responsibilities and capabilities) and
      process (e.g. utilising a clear referral pathway) factors that influence
      teamworking, as CMHTs develop over time. CONCLUSIONS: Completion by CMHT members
      of teamworking and other evaluative measures can assist teams in highlighting
      potential interventions that may improve recovery-focused team functioning and
      effectiveness.

PMID- 30189473
TI  - Media representation of depression in young people: a corpus-based analysis of
      Irish newspaper coverage.
AB  - OBJECTIVES: Newspaper media are an important source of information regarding
      mental health and have a significant influence on people's awareness of, and
      decision making around, mental health issues. Depression in young people has seen
      increasing media attention in recent years, but few studies have examined media
      representation of mental health, specifically in young people. The current study
      used a quantitative approach to examine the words used in reports concerning
      depression in young people, in Irish broadsheets, published between 2007 and
      2011. METHOD: A sample of 269 texts, containing 176 223 words, was collected from
      three Irish broadsheet newspapers, using the search terms 'depression' or
      'depressed' or 'mental health' and 'youth' or 'young people'. A corpus-based
      approach was used to examine word frequencies, clusters and keywords. RESULTS:
      The analysis identified textual patterns, suggesting recurring associations
      between youth depression and suicide, and, to a lesser extent, alcohol use and
      bullying. Keywords relating to emotional distress and symptoms of depression were
      less frequent and sometimes associated with constructions inferring lack of
      agency (such as 'suffering from'). A focus on the role of the parents was also
      evident. Of the professions mentioned, psychiatrists were referred to most often.
      CONCLUSIONS: The analysis suggests that media coverage of depression in young
      people accurately reflects concerns reported in surveys by young people, but
      provides less information that might help in recognising depression in a young
      person.

PMID- 30189474
TI  - Paediatric psychotropic prescribing practices in Ireland.
AB  - OBJECTIVES: This study describes the attitudes, knowledge and prescribing of
      psychotropic medication in children. METHOD: A study-specific questionnaire was
      mailed to all child psychiatrists, paediatricians and a group of registered
      general practitioners (GPs) from a selected Child and Adolescent Mental Health
      Services catchment area. RESULTS: In the 116 respondents who replied (39%
      response rate), psychotropic medication was generally valued and used by all
      groups (70.1%). Respondents believed that the majority (61.9%) of their non
      medical colleagues would also value/support the use of medication and this
      endorsement influenced the respondents' prescribing rates. Initiating medication
      was viewed as the province of child psychiatry (78.6%). Medication is felt to be
      justified in a wide variety of mental health disorders, their use being reserved
      for severe presentations, with psychostimulants and selective serotonin reuptake
      inhibitors being most used. A significant number of GPs (60.9%) and
      paediatricians (63.4%) were felt to be lacking in competence in psychotropic
      prescribing, with a general request for more seminars in this area (61.5%) with
      almost half (45%) of them believing that they would prescribe more often.
      CONCLUSION: The use of psychotropic medication in children remains a valued and
      common practice in Ireland. Attitudinal and practice differences across
      professional groups exist, and although the experience is one of relative safety
      there was a strong desire for further education leading to a perceived increase
      in utilisation. The impact of perceived public opinion regarding psychotropic
      prescribing along with a lack of competence may represent a major barrier to
      effective prescribing, thus highlighting the importance of ongoing professional
      development and increased public health initiatives to increase knowledge and
      understanding in this increasingly important area.

PMID- 30189475
TI  - Can the new epidemiology of schizophrenia help elucidate its causation?
AB  - The supposed universality of the incidence and prevalence of schizophrenia has
      been seriously challenged. It is now widely accepted that the life-time
      prevalence and incidence of this disorder vary considerably in time and place. As
      a result, there has been renewed interest in environmental causation of
      schizophrenia. There are few extant formulations that have successfully
      integrated the available new evidence into a coherent theory for its causation.
      The outgroup intolerance hypothesis is an attempt to integrate this evidence. It
      proposes that schizophrenia is the result of a mismatch between the social brain
      as shaped by evolution and the new social conditions of the post-neolithic. The
      hypothesis can provide an explanation for (i) the higher risk to migrants, (ii)
      the ethnic density phenomenon, (iii) the increased risk to individuals who have
      grown up in cities and (iv) the putative low risk in hunter-gatherer societies.
      Evidence is presented from a range of disciplines and sources including
      epidemiology, psychopathology, social psychology and clinical trials in support
      of this hypothesis. A range of testable predictions follow from the hypothesis.

PMID- 30189476
TI  - An analysis of 100 referrals for depression from primary care to an adult mental
      health service.
AB  - OBJECTIVES: Improving the interface between primary care and mental health
      services is a key target in current healthcare policy in Ireland. This study
      examines the content of referrals from primary care to a community mental health
      service for apparent depression. METHOD: We retrospectively reviewed the clinical
      records of 100 patients with depression who consecutively attended a specialist
      mental health service in Ireland's midwest region. Records were reviewed for
      demographic and clinical information provided by the doctor at the time of
      referral, subsequent service engagement, diagnosis and treatment initiated.
      RESULTS: There was considerable variation in the content and presentation of
      information contained in referral letters. Eleven per cent used structured HSE
      mental health referral forms. Seventy-six per cent of referrals contained clear
      information regarding name, address, symptoms and treatment previously initiated.
      Specifically, low mood, biological symptoms of depression and illness severity
      were documented in 43%, 34% and 27%, respectively. Suicide risk was documented in
      20%. More detail was significantly associated with more severe illness. At
      initial specialist assessment, 71% had commenced antidepressant treatment, with
      11% having received an adequate trial of a first antidepressant and 3% an
      adequate trial of two antidepressants. Two-thirds were diagnosed with
      mild/moderate depression. Initiation of antidepressant treatment was linked to
      subsequent diagnosis of depressive illness by mental health services (p < 0.001).
      CONCLUSIONS: Our findings indicate variable referral practices from general
      practice to mental health in our region. Most referrals were for mild to moderate
      depression. Poor access to psychological services locally may be a key factor in
      this phenomenon.

PMID- 30189477
TI  - Non-graduate and graduate entry medical students attitudes to psychiatry.
AB  - OBJECTIVE: Graduate entry medical students' views of psychiatry may differ from
      those of school leavers. This study hypothesised that (i) exposure to a
      psychiatry attachment is associated with a positive change in attitudes towards
      psychiatry in both graduate entry and non-graduate entry students, (ii) graduate
      entry students exhibit a more positive attitude to psychiatry compared to non
      graduate entry students and (iii) graduate entry students are more interested in
      a career in psychiatry than non-graduate entry students. METHODS: In this study
      247 medical students (118 females and 129 males) completing their psychiatry
      rotation were invited to complete questionnaires examining career choice,
      attitudes to psychiatry and career attractiveness for a range of specialties
      including surgery, medicine, general practice and psychiatry before and after
      their psychiatry attachment. Questionnaires were distributed prior to
      commencement of their attachment and redistributed on the final day of the
      attachment. RESULTS: Of the 165 participants in the study, 75 students entered
      medicine via the traditional route (without a primary degree), 49 entered via the
      graduate entry programme and 41 had a primary degree. Overall, medical students
      displayed positive attitudes towards psychiatry. However, while there was an
      improvement in attitudes towards psychiatry and the career attractiveness of
      psychiatry on completion of the rotation, no differences were found between
      graduate and non-graduate entry students. Psychiatry and general practice had
      lower ratings for career attractiveness than other specialities. No significant
      changes were found in the first and second choice of specialty. CONCLUSION: Our
      results show that improvements in attitude and career attractiveness do not
      necessarily correlate with increased choice of psychiatry as a specialty.
      Graduate entry has been considered a possible opportunity for increasing
      recruitment in psychiatry but our results suggest that this may not be the case.
      Follow-up studies are required to determine whether career attractiveness
      correlates with future career choice.

PMID- 30189478
TI  - Psychiatric nurses' attitudes towards children visiting their parents in
      psychiatric inpatient units.
AB  - BACKGROUND: The provision of care for children of parents with a mental health
      problem is an area that is frequently neglected by health-care practitioners.
      OBJECTIVES: The aim of the overall study was to explore psychiatric nurses'
      knowledge of, attitudes and practice towards the support needs of children whose
      parent has a mental health problem. This paper specifically addresses the views
      of psychiatric nurses towards children visiting their parent in a mental health
      inpatient facility. METHOD: This study employed a self-completion survey design
      with a sample of 114 registered psychiatric nurses from one integrated mental
      health service in Ireland. RESULTS: The majority of participants were in favour
      of children visiting their parent when in hospital, but were of the view that the
      visiting areas should be away from the main ward location and designed to be
      child-friendly. Many expressed concerns about the standard of visiting facilities
      and worried about the potentially negative impact of a visit on the child's well
      being. In relation to education on child-care issues, a significant majority of
      the participants reported not having received any education in the child-care
      issues identified and, as a likely consequence, rated their knowledge as
      insufficient. CONCLUSIONS: This study highlights the need for further work in the
      areas of practitioner education, child-friendly visiting facilities, and the
      development of policy and practice guidelines around children whose parents
      experience a mental health problem.

PMID- 30189479
TI  - Patient satisfaction with psychiatric outpatient care in a university hospital
      setting.
AB  - OBJECTIVES: To measure patient satisfaction with psychiatric outpatient care in a
      university hospital setting. We wished to ascertain whether there was an
      association between increased patient satisfaction and background factors such as
      demographic details, diagnosis and patient preference for outpatient treatment in
      a hospital or a community setting. METHODS: We conducted a cross-sectional survey
      of individuals' satisfaction levels with their outpatient treatment. Outpatients
      were invited to complete the Client Satisfaction Questionnaire-8 (CSQ-8), a well
      validated self-report instrument, along with some additional questions on their
      attitudes to the service. RESULTS: One hundred and sixty-two respondents had a
      mean total CSQ-8 score of 26.7 (s.d. = 4.6) indicating a moderate to high level
      of satisfaction with outpatient care. Ninety percent of patients were satisfied
      with their psychiatric outpatient care. There were no significant
      sociodemographic or clinical associations with satisfaction levels identified.
      Sixty one percent of patients were in favour of retaining outpatient care in the
      university hospital. CONCLUSIONS: This study demonstrates high satisfaction
      levels with psychiatric outpatient care in a university hospital setting. The
      majority of patients expressed a preference for maintaining outpatient care in
      the general hospital setting, rather than transferring to a stand-alone mental
      health facility in a suburban setting.

PMID- 30189480
TI  - Psychiatric nurses' attitudes towards children visiting their parents in
      psychiatric inpatient units - Corrigendum.

PMID- 30189481
TI  - Implementing the Mental Health Act 2001 in Ireland: views of Irish general
      practitioners.
AB  - OBJECTIVES: The Mental Health Act 2001 introduced important reforms of Irish
      mental health law and services. This paper aims to provide an evidence-based
      exploration of general practitioners' views on the implementation of the Mental
      Health Act 2001. METHODS: We posted questionnaires to 1200 general practitioners
      in Ireland seeking their views on their experiences with the Mental Health Act
      2001. RESULTS: Eight hundred and twenty general practitioners (68.3%) responded.
      Among those who provided comments, a majority (75.2%) provided negative comments.
      The most commonly occurring themes related to difficulties with transport of
      patients to inpatient facilities, form filling, time requirements and
      administrative matters. Other negative comments related to general practitioner
      recommendations for involuntary admission, training, mental health tribunals,
      applications for involuntary admission and the position of children. Minorities
      provided neutral (18.0%) or positive comments (6.8%), chiefly related to user
      friendliness, transparency and improved communication. CONCLUSIONS: General
      practitioners highlight a need for greater training and clear guidelines in
      relation to the Mental Health Act 2001. Their forthright responses demonstrate
      deep engagement with the new legislation and eagerness to see the Mental Health
      Act 2001 realise its full potential to improve the involuntary admission process
      and protect human rights, in the best interests of patients.

PMID- 30189482
TI  - New guidelines on fitness to drive: what do they mean to psychiatrists and their
      patients?
AB  - The publication of the new guidelines is a welcome step, bringing more lucidity
      to the subject and providing useful guidance to clinicians. However, the
      guidelines pose new and unique responsibilities on mental health services with
      resulting training needs, resource issues and ethical issues. We propose a
      collaborative model based on the development of regional specialised teams to
      perform this task. This may prove to be a more suitable and cost effective option
      in the long run.

PMID- 30189483
TI  - Smoking impedes executive function and related prospective memory.
AB  - OBJECTIVE: This study assessed both executive function (EF) and prospective
      memory (PM) in a group of current smokers (CS) to observe whether deficits in
      both sets of memory processes co-existed in smokers, comparing this group with a
      group who had never smoked (NS). METHOD: An existing-groups design was used to
      compare smokers with the NS group on a Reserve Digit Span Task (RDST) that
      measured EF and the Cambridge Prospective Memory Test (CAMPROMPT) measuring PM.
      Age, mood, other drug use and IQ were also measured and controlled for in the
      study. RESULTS: After omitting anyone using an illegal substance and observing no
      between-group differences in age, gender, anxiety, depression, alcohol use and
      IQ, the CS group performed significantly worse on the RDST and recalled
      significantly fewer time-based and event-based tasks on CAMPROMPT, compared with
      the NS group. CONCLUSIONS: Both EF and PM deficits were evident in the same
      cohort of CS when compared with a NS group, a finding which is novel in the
      current literature. Since both EF and PM are interrelated in that they share
      common resources in the brain, the finding that both sets of deficits co-existed
      in smokers suggests that persistent cigarette smoking impedes these underlying
      resources.

PMID- 30189484
TI  - The impact of a change in prescribing policy on antipsychotic prescribing in a
      general adult psychiatric hospital.
AB  - OBJECTIVES: To examine the impact of a change in local prescribing policy on the
      adherence to evidence-based prescribing guidelines for antipsychotic medication
      in a general adult psychiatric hospital. METHODS: All adult in-patients had their
      clinical record and medication sheet reviewed. Antipsychotic prescribed, dose
      prescribed and documented indications for prescribing were recorded. This was
      done before and after the implementation of the change in hospital antipsychotic
      prescribing policy. RESULTS: There were no significant differences in age, sex,
      Mental Health Act status, psychiatric diagnosis or documented indications for
      prescribing multiple or high dose antipsychotics between the two groups. There
      was an increase in the preferential prescribing of multiple second-generation
      antipsychotics (p=0.01) in the context of a significant reduction in the
      prescribing of multiple antipsychotics overall (p=0.02). There were no
      significant reductions in prescribing of mixed generations of antipsychotics
      (p=0.12), high dose antipsychotics (p=1.00) or as required (PRN) antipsychotics
      (p=0.74). CONCLUSIONS: Changes in local prescribing policy can improve adherence
      to quality prescribing guidelines and cause clinically significant improvements
      in patterns of prescribing in a general adult psychiatric hospital.

PMID- 30189485
TI  - APSI: a proposed integrative model for suicide prevention.
AB  - BACKGROUND: Deaths by suicide have been increasing in recent years in Ireland,
      many of whom have co-morbid mental health difficulties and/or have attended
      primary care services 1 month before death. Aims To profile how 'Access to
      Psychological Services Ireland' (APSI) provides stepped-care therapies for mild
      to-moderate adult mental health presentations and the potential effectiveness of
      this model based on comparison to a review of evidence-based strategies in
      suicide prevention. A secondary aim is to highlight how APSI has the potential to
      target those at risk of suicide and provide an integrative after-care service to
      complement secondary care mental health services. Findings In a context of inter
      agency working, APSI provides an integrated continuum of suicide prevention
      interventions that map onto or intervene across the continuum of suicide
      behaviour. Hence, APSI appears to implement what the literature suggests will
      work in preventing suicide. However, outcome research is needed to establish
      APSI's impact in preventing suicide. Recommendations It is recommended that Irish
      based research is conducted to establish APSI's impact in preventing suicide with
      a view to rolling out APSI as a national mental health clinical care programme.

PMID- 30189486
TI  - Gambling: an Irish perspective.
AB  - Gambling legislation in Ireland has not been amended for the last several
      decades. The proposed Gambling Control Bill 2013 provides the opportunity to
      enact a bill in accordance with the current trends in gambling. The
      classification of Gambling Disorder in DSM 5 under Substance Use Disorders in
      2013 highlights the addiction potential of gambling and the perils associated
      with the same. This editorial discusses the prevalence of gambling disorders, its
      societal implications, mental health conditions co-morbid with gambling
      disorders, screening tools available for gambling disorders, and the treatment
      options available for gambling disorders at present. Furthermore, factors to be
      considered before enacting the proposed Gambling Control Bill 2013 into
      legislation have also been discussed.

PMID- 30189487
TI  - Understanding bereavement-related depression: the polemical journey of DSM-5.
AB  - OBJECTIVE: This paper will bring you on a polemical journey to understand the
      issues related in conceptualizing bereavement-related depression. METHOD: A
      critical narrative review was carried out to evaluate arguments and controversies
      surrounding DSM-IV classifications of bereavement exclusion for the diagnosis of
      major depressive disorder (MDD). Result Available studies that are associated
      with bereavement exclusion criteria, the open trials and treatments with the
      implications of such conceptualizations and the current removal of the
      bereavement exclusion from MDD in DSM-5 were addressed. CONCLUSION: The review
      highlights the never-ending polemical journey of conceptualizing any mental
      disorders, bereavement-related depression included.

PMID- 30189488
TI  - Economic evaluation of liaison psychiatry services.

PMID- 30189489
TI  - The effectiveness of a brief intervention to reduce alcohol consumption in
      pregnancy: a controlled trial.
AB  - OBJECTIVES: Alcohol consumption during pregnancy potentially has significant
      effects on both mother and baby. The aim of the study was to determine the
      effectiveness of a brief intervention to reduce alcohol consumption during
      pregnancy. METHODS: This study was performed at the outpatient antenatal clinics
      of a large academic maternity teaching hospital in Dublin city centre. Six
      hundred and fifty-six women who drank alcohol before pregnancy were recruited at
      their first antenatal clinic visit. Drinking patterns before pregnancy, since
      becoming pregnant, and in later pregnancy (at ~32 weeks of gestation) were
      assessed using the Alcohol Use Disorders Identification Test (AUDIT). A
      controlled study was conducted - participants were allocated to either the brief
      intervention group (screening and 5 minutes of non-directive discussion of their
      drinking pattern) or a control group (screening and treatment as usual). RESULTS:
      Before pregnancy, 57% of women consumed five or more units of alcohol per
      drinking occasion (i.e. binge drinking); during pregnancy, the rate of binge
      drinking fell to 4.8%. Sixty per cent of women who drank before pregnancy ceased
      drinking when pregnant, and a further 9% reduced their intake substantially. Four
      hundred and ninety-nine women were followed up in later pregnancy. The brief
      intervention did not produce any significant reduction in alcohol consumption
      above that attributable to pregnancy and comprehensive screening in antenatal
      care. Larger reductions in alcohol intake during pregnancy were associated with
      younger age, non-Irish nationality and greater intake of alcohol before first
      antenatal clinic visit. CONCLUSION: Pregnancy itself produces abstinence and
      large reductions in alcohol consumption, even among women who drink relatively
      heavily. Consequently, a universal screening and brief intervention programme is
      not warranted but screening and targeted interventions could be appropriate such
      as repeated interventions for those who continue to binge drink. Future research
      could include evaluating interventions for those women who continue to binge
      drink during pregnancy and exploring ways of maintaining reductions in alcohol
      consumption among women who decreased consumption during pregnancy.

PMID- 30189490
TI  - Recruitment difficulties in screening for mental health difficulties in parents
      of children attending a child and adolescent mental health service.

PMID- 30189491
TI  - Co-prescribing of linezolid and serotonergic agents in a general hospital
      setting.
AB  - BACKGROUND: Co-prescription of linezolid and serotonergic agents (SSRIs, SNRIs,
      NaSSA, TCAs) can lead to serotonin syndrome, this study seeks to identify
      prescribing practise of these agents. METHODS: Study of all general hospital
      inpatients prescribed intravenous linezolid in a 3-month period, using drug
      charts and clinical notes. RESULTS: Co-prescription occurred in 20% with SSRIs
      most frequently concurrently used. There were no cases of serotonin syndrome.
      There was no evidence in clinical notes of vigilance for potential interaction.
      CONCLUSION: Co-prescription is common; awareness of potentially serious
      interaction is not evident in current practice.

PMID- 30189493
TI  - Attention-deficit hyperactivity disorder (ADHD) in adults attending addiction
      treatment in Ireland: preliminary international ADHD in substance-use disorders
      prevalence study (IASP) results.
AB  - OBJECTIVES: Attention-deficit hyperactivity disorder (ADHD) is a neuro
      behavioural disorder characterised by early onset of persistent inattention
      disorganisation and hyperactivity-impulsivity. Symptoms causing significant
      impairment in psychosocial function commence in childhood and heighten the risk
      for early substance experimentation and potential development of substance-use
      disorders (SUD). The research aimed to estimate the occurrence of adult attention
      deficit hyperactivity disorder (ADHD) in new treatment cases of adults attending
      addiction treatment services. METHODS: The Adult ADHD Symptoms Rating Scale
      (ASRS) self-administered questionnaire was administered on entry and 2 weeks
      later for first admissions to inpatient and outpatient addiction treatment
      settings The ASRS is a validated and reliable 18-item self-report scale derived
      from the DSM-IV-TR diagnostic criteria for ADHD, comprising nine items on
      inattention and nine items on hyperactivity/impulsivity. RESULTS: A total of 47
      new treatment cases took part in the study. The occurrence of ADHD among SUDs in
      this sample was 13% (n = 6). Four of the participants were being treated for
      Problem Poly Substance use, whereas two participants were being treated for
      Problem Drug use. None of the participants screening positive for ADHD were being
      treated for Problem Alcohol use. Of the positively screened cases, all were male,
      predominantly single and unemployed. CONCLUSIONS: The ASRS screening instrument
      may be a useful tool to detect ADHD co-morbidity in SUD treatment-seeking cases.
      More research is needed to appropriately develop the SUD treatment pathways for
      adolescent and adult ADHD sufferers in Ireland.

PMID- 30189492
TI  - Embracing performance measurement in mental health services.
AB  - OBJECTIVES: Performance measurement (PM) is central to the current Irish health
      service policy. However, PM within the Irish mental health services has not been
      fully implemented. These services lack a national comprehensive suite of
      performance indicators (PIs). Those indicators that are measured do not tend to
      reflect the objectives of the managers and staff measuring them. To overcome
      these challenges, this article suggests a suite of measures and aims to provide a
      practical guide to PM for managers and staff. METHOD: A narrative review of a
      range of policy documents and articles, relevant to PM in the Irish mental health
      services, was undertaken. Findings The search produced a number of themes
      illustrating the limitations of the current set of PIs for Irish mental health
      services, in particular the need for comprehensive PIs, including structure,
      process and outcome PIs. This informed the development of a suite of proposed PIs
      for mental health services. A number of additional themes highlighted the
      criticisms associated with the top-down approach used to implement PM. Drawing
      from these themes, a bottom-up approach to PM is proposed. CONCLUSION: Although
      this review was selective in nature, it illustrates how the concerns of
      clinicians and service managers can be integrated with the priorities of the
      Health Service Executive and the Department of Health. This presented the suite
      of PIs and the practical guide that provide useful PM tools. While also
      applicable at a national level, this paper provides guidance for service managers
      as to the process of establishing and implementing a suite of PIs within their
      own service.

PMID- 30189494
TI  - Examining IQ among a clinical sample of preschool children with autism spectrum
      disorder over time.
AB  - BACKGROUND: The cognitive functioning of children who received a diagnosis of
      autistic spectrum disorder (ASD) during the preschool years was assessed at the
      time of diagnosis (Time 1) and reassessed, on average, 3 years and 5 months later
      (Time 2). METHOD: A total of 50 children were assessed (76% male, n = 38); the
      group had an average age of 4 years 3 months at Time 1 and 7 years 8 months at
      Time 2. RESULTS: There was a significant positive relationship (r = 0.791, p <
      0.01) between the group's Full Scale Intelligence Quotient (FSIQ)/Developmental
      Quotient (DQ) at Time 1 and at Time 2. Results indicated a significant increase
      in FSIQ/DQ over time for the total group and for both the High Functioning (IQ ?
      70) and Low Functioning (IQ < 70) groups. Of the total samples, 32% showed a
      clinically significant change in FSIQ/DQ of 15 points or more from Time 1 to Time
      2. When age at Time 1 was included as a covariate, no significant difference was
      identified for change in FSIQ over time. The practical implications of the
      findings are discussed.

PMID- 30189495
TI  - Survey examining the views of Adult Psychiatry Consultants and Senior Registrars
      regarding ADHD.
AB  - OBJECTIVES: Attention deficit hyperactivity disorder (ADHD) persists into
      adulthood in ~2/3 of patients, yet services for adults are lacking in Ireland.
      This may involve negative attitudes and beliefs as to the validity of ADHD or
      lack of knowledge and training in its treatment. The objectives of this study are
      to explore the views of Adult Psychiatrists regarding ADHD knowledge and the
      treatment options available and pursued in Ireland. METHODS: A questionnaire was
      constructed based on the stated aims of the study, and was either posted, emailed
      or handed to 400 Consultants and Senior Registrars throughout the Republic of
      Ireland between February and December 2011. A total of 92 questionnaires were
      returned (23%); one was excluded from analysis due to insufficient information
      entered by the respondent. RESULTS: Seventy-five per cent of respondents
      correctly estimated the prevalence rates of adult ADHD to be under 3%, but stated
      it is currently under-diagnosed (77%). Seventy-four per cent indicated that Adult
      ADHD should be a diagnostic category in the Diagnostic and Statistical Manual,
      5th Edition (DSM V). Sixty-six per cent of respondents were willing to accept
      referrals of childhood ADHD for ongoing care and a similar number for new ADHD
      assessments (61%). Less than half (42%) surveyed had actually diagnosed ADHD and
      of these, only 33% felt confident in managing ADHD in their patients.
      CONCLUSIONS: Although there is a general willingness to offer services for new
      and existing ADHD cases and a recognition that Adult ADHD is valid and under
      diagnosed, the low confidence levels when treating ADHD and the perception of
      under-diagnosis suggests a role for further training and links between child and
      adult services.

PMID- 30189496
TI  - Psychotropic prescribing in the oldest old attending a geriatric psychiatry
      service: a retrospective, cross-sectional study.
AB  - OBJECTIVE: More people are living beyond their 90s, yet this group has not been
      much studied. This study aimed to describe a sample of non-agenarians and
      centerians attending an old age psychiatry service with a focus on
      pharmacotherapy. METHODS: Retrospective, cross-sectional survey of patients aged
      >90 in contact with the Department of Old Age Psychiatry in a university hospital
      over a 1-year period. Results were compared with the Beers, the Canadian and
      Screening Tool of Older Persons' potentially inappropriate Prescriptions (STOPP)
      criteria. RESULTS: A total of 65 nonagenarians or centerians were identified
      (mean age 93, 82% female). The majority (65%) resided in a nursing home; dementia
      was the most common diagnosis (77%), followed by depression (29%). The most
      commonly prescribed psychotropics were antidepressants (58%), followed by
      antipsychotics (45%), hypnotics (42%), anti-dementia agents (31%) and anxiolytics
      (26%). Overall, patients were on a mean of 2.1 (S.D. 1.3, range 0-5)
      psychotropics and 4.99 (S.D. 2.7, range 0-11) non-psychotropics. Mean Mini Mental
      State Examination (MMSE) score was 15 (S.D. 8.1). Increasing anticholinergic
      burden was negatively associated with MMSE scores (B = -1.72, p = 0.013).
      Residing in a nursing home was associated with a higher rate of antidepressant
      [OR 5.71 (95% CI 1.9-17.4)], anxiolytic [OR 13.5 (95% CI 1.7-110.4)] and
      antipsychotic [OR 3.4 (95% CI 1.1-10.4)] use. Potentially inappropriate
      prescribing included long-term benzodiazepine use (26%) and long-term
      antipsychotic use (25%). CONCLUSIONS: Our sample had a high psychiatric morbidity
      burden with high levels of psychotropic use. Ongoing review and audit of
      psychotropic use in elderly patients can identify potentially inappropriate
      prescribing in a group vulnerable to high levels of polypharmacy and extended
      psychotropic use.

PMID- 30189497
TI  - Transcultural perspectives of sensory phenomena in Arab Muslim patients suffering
      from obsessive-compulsive disorder.
AB  - The manifestations of obsessive-compulsive disorder (OCD) may vary across
      cultures. This is article discusses six case presentations of Arabic Muslim
      people suffering from OCD and is closely associated with practising religious
      rituals which tend to dominate the clinical picture. This is particularly
      relevant to sensory phenomena, which are often perceived as abnormal perceptions
      or hallucinations. We conclude that these phenomena are not uncommon in OCD and
      have relevant cultural, diagnostic and therapeutic issues in some cases.

PMID- 30189498
TI  - 'Show me the money': improving the economic evaluation of mental health services.
AB  - BACKGROUND: Compared with the United Kingdom, mental health services in Ireland
      are under-funded and under-developed. This may be partly due to the neglect of
      economic analyses concerning mental health services in Ireland, as few policy
      makers would invest in the sector without evidence that such investment
      represents 'value-for-money' economically. Aim The aim of this paper is to
      highlight how mental health services can conduct economic service evaluations
      that ultimately will drive the policy-making agenda and future governmental
      investment. METHODS: A guide to the economic evaluation of mental health
      services, based on a narrative review of relevant policy documents and papers, in
      an Irish context. RESULTS: Three types of economic analyses that can be
      undertaken within mental health services are outlined: (a) cost-benefit analysis,
      (b) cost-utility analysis and (c) cost-minimisation analysis. In addition, a
      newly formulated questionnaire (i.e. the 'EcoPsy 12') is presented. CONCLUSIONS:
      Economic evaluations of mental health services can provide re-assurances to
      policy-makers that (much-needed) investment in such services is economically
      viable.

PMID- 30189499
TI  - Assessing metabolic syndrome in people with ID (intellectual disabilities) on
      antipsychotic medication.
AB  - : Aims To identify whether clinical information routinely collected and recorded
      on clinical files is available for the identification of metabolic syndrome and
      to assess the prevalence of risk factors for the syndrome in a sample of people
      with intellectual disabilities (ID) and mental illness treated with antipsychotic
      medication. METHODS: A retrospective analysis was performed for 76 adults with ID
      and comorbid mental illness, for whom treatment with antipsychotic medication was
      established. Statistical analysis was performed using SPSS 16.0. The Student t
      test for parametric data and chi 2-test for non-parametrical data were used.
      RESULTS: Five of the six criteria for metabolic syndrome were available in all or
      a high proportion of the files, however no measurement for waist circumference
      was recorded in any of the files. Aripiprazole appears to be the least risky
      antipsychotic for metabolic syndrome. CONCLUSION: It is important to develop a
      systematic protocol to record diagnostic variables for metabolic syndrome in at
      risk populations such as those with ID and mental illness treated with regular
      antipsychotics.

PMID- 30189500
TI  - A review of prescribing patterns in 24-hour nurse-staffed community residences in
      Ireland.

PMID- 30189501
TI  - A scoping review of the literature on the involvement of service users in
      personality disorder services.
AB  - BACKGROUND: Service user involvement is receiving increasing support from mental
      health policy makers, service planners and research commissioners. However, we
      lack a good understanding of the nature and extent to which service users are
      involved in personality disorder (PD) services and the effects of involvement in
      these services. OBJECTIVES: To review and appraise published sources; increase
      understanding about service user involvement in PD services; and highlight
      knowledge gaps and related issues. METHODS: A scoping review methodology was
      adopted. Data were 'charted' to illustrate the landscape of writings and views
      and a qualitative analysis synthesized the results in terms of key emergent
      themes. RESULTS: Only a small amount of published work was identified with
      significant gaps in the literature. Effects were reported mostly in terms
      processes and emotional and practical benefits for service users. Emergent themes
      were wellness and health, recruitment and support for service users. CONCLUSIONS:
      This scoping review uncovered a lack of published work despite service user
      involvement being a key strand of health policy. There is a need for outcomes
      focused research regarding service user involvement. Successful user involvement
      in PD services requires attention to be focused on the context, recruitment,
      support and 'wellness' of service users.

PMID- 30189502
TI  - An examination of childhood trauma in individuals attending an adult mental
      health service.
AB  - OBJECTIVES: Childhood sexual abuse has previously been associated with adult
      mental health difficulties, however, few studies have evaluated all forms of
      childhood maltreatment in individuals attending adult mental health services.
      Consequently, this study investigates the association of five forms of childhood
      trauma with a range of clinical symptoms and mental health disorders in 136
      individuals attending a mental health service in Ireland utilising the Childhood
      Trauma Questionnaire (CTQ). METHOD: One hundred and thirty-six patients attending
      the Roscommon Mental Health Services completed the CTQ and a number of additional
      psychometric instruments evaluating illness severity, impulsivity, disability and
      the presence of a personality disorder(s) (PD) to ascertain the prevalence of
      childhood trauma and any potential associations between childhood trauma and a
      range of demographic and clinical factors. Result Seventy-six per cent of
      individuals reported childhood trauma, with emotional neglect most frequently
      reported (61%). Individuals who had experienced childhood trauma had higher rates
      of clinical symptoms, distress and impulsivity. Substance abuse and paranoid,
      borderline and antisocial PDs most associated with childhood trauma. CONCLUSION:
      This study demonstrates the need to routinely elicit information on all forms of
      childhood traumatic experiences from patients.

PMID- 30189503
TI  - The role of a neuropsychiatry clinic in a tertiary referral teaching hospital: a
      2-year study.
AB  - OBJECTIVES: Mental disorder is common among individuals with neurological
      illness. We aimed to characterise the patient population referred for psychiatry
      assessment at a tertiary neurology service in terms of neurological and
      psychiatric diagnoses and interventions provided. METHODS: We studied all
      individuals referred for psychiatry assessment at a tertiary neurology service
      over a 2-year period (n= 82). RESULTS: The most common neurological diagnoses
      among those referred were epilepsy (16%), Parkinson's disease (15%) and multiple
      sclerosis (8%). The most common reasons for psychiatric assessment were low mood
      or anxiety (48%) and medically unexplained symptoms or apparent functional or
      psychogenic disease (21%). The most common diagnoses among those with mental
      disorder were mood disorders (62%), and neurotic, stress-related and somatoform
      disorders, including dissociative (conversion) disorders (28%). Psychiatric
      diagnosis was not related to gender, neurological diagnosis or psychiatric
      history. CONCLUSION: Individuals with neurological illness demonstrate
      significant symptoms of a range of mental disorders. There is a need for further
      research into the characteristics and distribution of mental disorder in
      individuals with neurological illness, and for the enhancement of integrated
      psychiatric and neurological services to address the comorbidities demonstrated
      in this population.

PMID- 30189504
TI  - The 'G' men: a profile of GBL/GHB users in an area of high drug-related
      mortality.
AB  - OBJECTIVES: Gamma-butyrolactone/gamma-hydroxybutyrate (GBL/GHB) and related
      analogues are increasingly misused. The study reports on patient characteristics,
      nature and pattern of use, complications and comorbidity for a cohort of patients
      presenting to a large Substance Misuse Service in Brighton and Hove City. METHOD:
      A retrospective case-note review of routinely collected clinical data on patients
      with primary GBL/GHB misuse. RESULTS: In all, 24 individuals were male and 3
      female, with a mean age of 34 years. A total of 21 males identified themselves as
      gay and 1 female as bisexual. Just over half (15, 56%), respectively, were living
      in stable accommodation and were in employment or third-level education. In all,
      22 (81%) met criteria for physical dependence and two-thirds (18, 67%) had
      experienced overdose. The group was using large amounts of GBL (mean 53 ml/day)
      with a significant number (25, 93%) using 'around the clock' (every 1-3 hours).
      Over one-third (10, 37%) had a diagnosis of HIV and with 24 (89%) having a
      presumptive diagnosis of anxiety disorder. CONCLUSIONS: A profile of gay men with
      relatively stable lifestyles, but nevertheless with a high rate of complication
      of GBL/GHB use and with a significant comorbidity (HIV and psychological
      problems) was identified. The need for integrated specialist services and the
      importance of liaison with Emergency Departments and HIV services is highlighted.

PMID- 30189505
TI  - Pregabalin abuse for enhancing sexual performance: case discussion and literature
      review.
AB  - Pregabalin is a gamma-aminobutyric acid analogue that is primarily prescribed in
      psychiatry for management of generalized anxiety disorder. The belief in its low
      potential for abuse has placed it in a superior position to other anxiolytic
      agents. However, more recent, concerns have been raised about the addictive
      potential of pregabalin. This problem has not received much attention nor has the
      mechanism of its development. There is also a lack of understanding of the
      difference in the experience of abusing pregabalin in contrast to abusing other
      illicit drugs. We report the case of a 55-year-old patient with a background
      history of multiple psychoactive substances misuse who elaborated on his own
      personal experience of pregabalin abuse. He consumed a month's supply of this
      medication over 2 days and realized an enhancement in sexual desire and
      excitement. This effect should be considered when prescribing pregabalin.

PMID- 30189506
TI  - Voting and mental illness: the silent constituency.
AB  - Mental illness has been long associated with denial of certain human rights,
      social exclusion and political disempowerment. Too often, the effects of adverse
      social, economic and political circumstances, along with stigma, constitute a
      form of 'structural violence', which impairs access to psychiatric and social
      services, and amplifies the effects of mental illness in the lives of sufferers
      and their families. Existing literature indicates that voting rates are low among
      people with mental illness and, whereas voting preferences in the mentally ill
      may tend towards the liberal end of the political spectrum, they do not differ
      dramatically from the overall population. Rates of voting could be improved by
      mental health service users, service providers, advocacy services and others
      through (a) improved awareness of voting rights; (b) provision of information,
      especially to inpatients;

PMID- 30189507
TI  - A survey of voting practices in an acute psychiatric unit.
AB  - The aim of this survey was to investigate the voting practices of patients on an
      acute psychiatric unit in the General Election 2011. Our survey showed that only
      10% of patients voted and many patients were unaware of their right to vote. We
      recommend that all patients should be routinely informed of their right to vote
      as part of their hospital admission. Voting should be facilitated by hospital
      staff and advocacy where practicable.

PMID- 30189508
TI  - Attitudes and experiences of nursing staff to the Mental Health Act 2001: lessons
      for future mental health legislation.
AB  - OBJECTIVES: The Mental Health Act 2001 was implemented in 2006 to bring Ireland
      into line with international practice and United Nations Conventions on Human
      Rights. Previous studies have reported some practical difficulties for the
      professionals involved. We wished to examine the experiences of nursing staff and
      the impact of the Act on clinical nursing practice since its implementation.
      METHOD: This cross-sectional survey was conducted by questionnaire. It contained
      questions examining training in and attitudes to the Act, and any resultant
      changes in nursing practise. RESULTS: A total of 317 questionnaires were
      returned. Of the nurses, 92% reported having received training in the Act, and
      56% of nursing staff believed that their workload had increased as a result of
      the change in legislation. Of those who made a comment, 76.5% were negative, with
      increased paper work, lack of clarity and an excessive focus on legalities being
      the most common difficulties reported. CONCLUSIONS: Nursing staff have shown
      mixed attitudes to the Mental Health Act 2001, but many of the difficulties
      encountered are similar to those experienced by other professionals.

PMID- 30189509
TI  - Compliance with the Data Protection Acts in a psychiatric department: a complete
      audit cycle.
AB  - : Aim 1) to assess compliance with the Data Protection Acts (DPA) by a Department
      of Psychiatry in a general hospital, 2) to implement measures that are likely to
      maximize compliance with the hospital data protection policy, 3) to close the
      audit cycle by assessing the impact of such measures on departmental compliance
      with the DPA over five months period. METHOD: An individual, anonymised staff
      questionnaire on data collection practices, procedure of disclosure of data to
      third parties and previous training on DPA was used to collect information from
      the department staff. The premises were inspected at different times over a week
      period using structured checklist. Default points were recorded during each
      inspection. Post-audit interventions included a mixture of educational
      interventions and practical solutions. A re-audited took place five months later
      using the same method. RESULTS: The baseline audit demonstrated significant lack
      of compliance with the DPA among staff members and lack of staff training on the
      DPA. Following the interventions, staff awareness of the requirements of the act
      rose which in turn lead to better adherence to recommend practices in data
      handling and to mean default points dropped significantly. Management of manual
      files appears to constitute the biggest problem in this audit. Daytime breaks
      were found to pose higher risk to stored data compared with before and after
      working hours. CONCLUSIONS: A combination of educational and practical
      interventions including training of staff on the DPA results in overall
      improvement in compliance and reduction in default points. However, management of
      manual (physical) data proves to be more difficult and hence will need more
      input.

PMID- 30189510
TI  - Understand me; believe in me; accept me as I am: perceptions of psychiatry of
      later life service.
AB  - : Context The emergence of mental health services for older people is a
      relatively recent development in Ireland. Therefore, it is important to determine
      strengths and limitations of this modern-day care service. A starting point is to
      enquire from those who have been in receipt of their service and/or their
      respective carers. Aim This study aims to identify and describe the perceptions
      and experiences of past service users (SUs) and their carers, while in receipt of
      services from an acute mental health day hospital for Psychiatry of Later Life
      and to explore their needs/supports. METHODS: A qualitative, exploratory,
      descriptive design was employed. Purposive sampling achieved a sample of 13 SUs
      and six carers. Inclusion criteria set were that the SU had a diagnosis of a
      psychiatric disorder; had the capacity to make an informed consent and
      communicate verbally and the SU was discharged from the service between January
      and July 2011. Finally, carers of SUs in receipt of the service during this time
      were also included. Data were subjected to thematic, field analysis. Findings
      'Person centredness' emerged as an overarching theme. Six inter-related subthemes
      revealing how SUs and carers viewed their care emerged from the interviews:
      'therapeutic engagement'; 'preservation of self-integrity'; 'collaborative care';
      'integrated care'; 'social gains'; and 'the relationship between the expectation,
      subsequent engagement and the perceived outcome of care'. CONCLUSIONS: Findings
      concluded that high levels of care exist within this service. Strengths lie in
      the development of a therapeutic relationship, preservation of self-integrity,
      social gains and robust elements of person-centred holistic, integrated and
      collaborative care Recommendations support the enhancement of a cohesive planned
      approach to admission, discharge/transition (integrated pathway).

PMID- 30189511
TI  - The digital age: is this the future of medical education? A cross-sectional study
      to assess medical students' opinions about e-learning in psychiatry undergraduate
      medical education.
AB  - OBJECTIVES: The main objectives were to assess medical students' opinions about e
      learning in psychiatry undergraduate medical education, and to investigate a
      possible relationship between learning styles and preferences for learning
      modalities. METHOD: During the academic year 2009/2010, all 231 senior Royal
      College of Surgeons in Ireland (RCSI) medical students in their penultimate year
      of study were invited to answer a questionnaire that was posted online on Moodle,
      the RCSI virtual learning environment. RESULTS: In all, 186 students responded to
      the questionnaire, a response rate of 80%. Significantly more students stated a
      preference for live psychiatry tutorials over e-learning lectures. Students
      considered flexible learning, having the option of viewing material again and the
      ability to learn at one's own pace with e-learning lectures, to be more valuable
      than having faster and easier information retrieval. CONCLUSION: Students prefer
      traditional in-class studying, even when they are offered a rich e-learning
      environment. Understanding students' learning styles has been identified as an
      important element for e-learning development, delivery and instruction, which can
      lead to improved student performance.

PMID- 30189512
TI  - The Isle of Wight Suicide Study: a case study of suicide in a limited geographic
      area.
AB  - BACKGROUND: Suicide is a major public health problem, with mental disorders being
      one of its major risk factors. The high incidence of suicide on the Isle of Wight
      has motivated this study, the first of its kind on suicide in this small
      geographic area. Aim The aim of the study was to identify socio-demographic and
      clinical risk factors for suicide in the population of service users and non
      service users, and gender-related characteristics of suicidal behaviour in a
      limited geographic region. METHOD: Data were collected on 68 cases of suicide
      (ICD-10*60-X84) from residents of the Isle of Wight District between January 2006
      and December 2009. All data were statistically analysed using Pearson's chi 2
      test and Yates' correction for continuity. RESULTS: The mean annual suicide rates
      over the period were 5.65 per 100 000 for women and 19.28 for men. Significantly
      (p=0.0006), more men than women (male/female ratio 3:1) died as a result of
      suicide. Relatively (p=0.07) more women (56.2%) than men (32.7%), and
      significantly more (p=0.05) service users (45.3%) than non-service users (13.3%)
      were unemployed. Significantly, more (p=0.0006) service users (64%) than non
      service users (20%) had a history of suicide attempts and relatively (p=0.06)
      more (50.9%) service users than non-service users (20%) had attended the accident
      and emergency department before their death; 69% had an adverse life event within
      a year before their suicide. Depression as the most common Axis-I illness was
      diagnosed in 36% of all; but significantly (p=0.008) more in women (66.6%) than
      men (17.3%). Relatively (p=0.07) more women (56.2%) than men (32.7%) have
      contacted services before their death. Suicide by hanging was the most common
      cause, accounting for the death of 71% of men and 50% of women. CONCLUSIONS: The
      study found that 80% of all suicides occurred in people suffering from mental
      disorder. Men are at a significant risk of suicide. Depressive disorders in women
      and stress-related disorders in men were the most common mental disorders.
      Treating mental disorders and co-morbid conditions seems to be one of the key
      elements in suicide prevention strategies.

PMID- 30189513
TI  - Attitudes to and practice of bibliotherapy among senior trainees in psychiatry.
AB  - OBJECTIVES: This study was to assess the attitudes and practice of, senior
      psychiatric trainees with regard to bibliotherapy. METHODS: A brief online survey
      was used to assess the attitudes to and practice of bibliotherapy among senior
      psychiatric trainees in Ireland. There were 34 responses out of 82 (response rate
      41.5%). Respondents were asked to indicate their agreement with three statements.
      RESULTS: The majority 27 (79.4%) strongly agreed or agreed that they were
      comfortable recommending books, with none strongly disagreeing and 4 (11.8%)
      disagreeing. Over half 20 (58.8%) of respondents strongly disagreed or disagreed
      that self help books could only be a poor substitute for psychotherapy or
      counselling, with none strongly agreeing and 2 (5.9%) agreeing. Many 19 (55.9%)
      disagreed or strongly disagreed that self help books could do more harm than
      good, with 8 (23.5%) agreeing or strongly agreeing. Finally respondents were
      asked to state their awareness of prescribe-a-book schemes. 4 (11.8%) respondents
      reported awareness, with 30 (88.2%) unaware of any such schemes. CONCLUSIONS:
      Although majority of senior psychiatric trainees were comfortable recommending
      self help books and did not consider them harmful, most were unaware of such
      schemes in Ireland.

PMID- 30189514
TI  - Clinical stability in the community associated with long-term approved leave
      under the Mental Health Act 2001.
AB  - : Introduction We present the case of a 27-year-old man with a background
      diagnosis of treatment resistant schizophrenia and absent insight who for the
      last 3 years has been residing in a high support residential setting on approved
      leave under the Mental Health Act (MHA) 2001. The case demonstrates how this man
      achieved clinical stability in the community with the assistance of long-term
      involuntary admission under the MHA 2001, in contrast to the previous years of
      his illness in which he had suffered multiple relapses of his psychotic illness
      with ssociated distress, poor self-care and repeated in-patient re-admissions. We
      discuss the equivalent use of community treatment orders in other jurisdictions
      and how the judicious use of approved leave under the MHA 2001 may be used as an
      alternative in Ireland where community treatment orders are not currently
      available. METHOD: Case Report. CONCLUSION: The case report highlights how the
      use of long-term approved leave under the MHA2001 may be used as alternative in
      Ireland to mimic CTOs for certain difficult to treat patients with psychotic
      illness who would benefit from ongoing treatment, but lack capacity to engage in
      such treatment due to persistent symptoms and lack of insight.

PMID- 30189515
TI  - Prevalence rates and risk factors for mental health difficulties in adolescents
      aged 16 and 17 years living in rural Ireland.
AB  - OBJECTIVE: This study sought to ascertain the prevalence rates and risk factors
      for a range of mental health difficulties, including suicidal ideation/self-harm
      among 16 and 17-year-old rural Irish adolescents, a vulnerable group in
      transition from childhood to adulthood. METHOD: Adolescents (n=237) took part in
      this cross-sectional study. Participants completed a questionnaire compendium
      consisting of generic questions on demographic information, use of mental health
      services and four normed questionnaires: The Youth Self-Report, the Children's
      Depression Inventory, the Coping Inventory for Stressful Situations-Adolescent
      and The Family Assessment Device. RESULTS: We found that 16.9% of adolescents
      reported clinically significant mental health difficulties. Significant gender
      differences were found on internalising and externalising difficulties. There
      were no gender differences in suicidal ideation or self-harm. Only 3.4% of
      adolescents were receiving professional help for mental health difficulties.
      Multiple regression analyses revealed that family dysfunction, emotion-focussed
      coping and poor academic competence were significant predictors of poorer mental
      health difficulties in both genders. Family dysfunction was the strongest
      predictor of mental health difficulties in males. Among females, emotion-focussed
      coping was the strongest predictor of internalising difficulties and depression.
      Social diversion (social support) was predictive of less internalising
      difficulties and depression for females. CONCLUSION: The study shows that a
      significant number of Irish 16 and 17 year olds have mental health difficulties,
      yet very few are receiving treatment. Emotion-focussed coping, family
      dysfunction, poor academic competence and less social support were important
      predictors of mental health difficulties. A new finding is the stronger
      association that family dysfunction has with poorer mental health in males than
      females, when controlling for academic competence and coping skills. The findings
      may have implications for psychological interventions.

PMID- 30189516
TI  - Dignity, human rights and the limits of mental health legislation.
AB  - A right is an entitlement that one may legally or morally claim. Human rights are
      of particular importance in mental health care owing to the existence of laws
      that permit involuntary admission and treatment under certain circumstances, and
      compelling evidence of persistent social exclusion of some individuals with
      mental disorder. Ireland's mental health legislation, which is currently under
      review, meets most international human rights standards in areas of traditional
      concern (involuntary admission and treatment) but not in other areas (especially
      social and economic rights). These deficits would be addressed, at least in part,
      by replacing the principle of 'best interests' with the principle of 'dignity' as
      the over-arching principle in Irish mental health legislation. Such a change
      would help ensure that decisions made under the legislation actively facilitate
      individuals with mental disorder to exercise their capabilities, help promote
      human rights and protect dignity. Even following such a reform, however, it is
      neither practical nor realistic to expect mental health legislation alone to
      protect and promote all of the broader rights of individuals with mental
      disorder, especially social and economic rights. Some rights are better
      protected, and some needs better met, through social policy, mental health policy
      and broader societal awareness and reform.

PMID- 30189517
TI  - Impact of receipt of private well arsenic test results on maternal use of
      contaminated drinking water in a U.S. population.
AB  - Exposure to inorganic arsenic in drinking water has known cancer and non-cancer
      health effects. However, no prior studies have addressed response to well water
      testing for arsenic during pregnancy, a time of known heightened risk perception.
      Using a US pregnancy cohort, we assessed the impact of receiving well water
      arsenic test results on subsequent use of arsenic-contaminated tap water. Study
      participants were 24-28 weeks' gestation at study entry and reported living in a
      residence served by a private, unregulated well. Upon enrollment participants
      provided a tap water sample which was tested for arsenic using ICP-MS. During
      pregnancy and every four months after, participants were asked their extent of
      tap water use for drinking, cooking and mixing infant formula. Logistic
      regression was used to estimate the odds of tap water use at one year post-partum
      in relation to baseline tap water use and arsenic concentration. Compared to
      those who used tap water <50% of the time, mothers who reported using tap water
      for drinking and cooking >50% of time in their prenatal questionnaire had 8.54
      times the odds of using their tap water at 1-year postpartum (95% CI: 5.37,
      13.60). After adjusting for frequency of prenatal tap water use, mothers were
      less likely to use tap water for drinking and cooking (OR = 0.34, 95% CI: 0.19,
      0.60) and for mixing formula (OR = 0.45, 95% CI: 0.24, 0.86) if the high arsenic
      concentration (>10 MUg/L) was known to them. Our findings suggest that providing
      well water test results during pregnancy may reduce subsequent maternal use of
      iAs contaminated tap water for drinking, cooking, and mixing infant formula.
      Public health implications are discussed.

PMID- 30189518
TI  - Concentrations, sources and health risk of nitrated- and oxygenated-polycyclic
      aromatic hydrocarbon in urban indoor air and dust from four cities of Nepal.
AB  - Although the fate and behavior of parent polycyclic aromatic hydrocarbon (PAHs)
      have been documented worldwide, the information about PAH-derivatives (NPAHs and
      OPAHs) is limited, especially in developing countries, including Nepal. Moreover,
      the greater parts of the investigations concentrating on NPAHs/OPAHs are on the
      air (borne) particulate phase only; and are primarily based on a limited number
      of compounds analyzed. Little is known about the environmental concentration,
      fate, and behavior of NPAHs and OPAHs in air gas phase and dust. In this study,
      the concentration, fate, spatial distributions of 26 NPAHs and 3 OPAHs in the air
      (n = 34) and dust (n = 24) were investigated in suspected source area/more
      densely populated areas of Nepal. Four critical source areas in Nepal were
      considered as it was conjectured that the urban areas are more prone to NPAH/OPAH
      contamination due to the high density of automobiles and industrial activities.
      Overall, the measured ?19NPAHs in air and dust were 5 and 2 times lower than
      their parent-PAHs, respectively. Highest levels of NPAHs/OPAHs were measured in
      Birgunj, followed by Kathmandu, Biratnagar, and Pokhara, respectively, while
      Biratnagar showed the highest level of ?OPAHs. 3-Nitrodibenzofuran (3-NDBF) was
      the most abundant NPAHs measured both in air and dust, whereas 9-Fluorenone (9
      FLUONE) prevailing OPAHs. The molecular diagnostic ratio (MDR) of 2
      Nitrofluoranthene/1-Nitropyrene indicated the contribution from secondary
      emission via photochemical reaction as the primary source of NPAHs, while solid
      fuel combustion and crop residue burning were identified as the essential sources
      of OPAHs. The human exposure to NPAH/OPAH through the different route of intake
      suggested dermal contact via dust as the primary pathway of NPAH/OPAH exposure
      for both adult and children. However, other routes of exposure, for instance,
      dietary intake or dermal absorption via soil may still be prominent in case of
      Nepal.

PMID- 30189519
TI  - A new insight into the strategy for methane production affected by conductive
      carbon cloth in wetland soil: Beneficial to acetoclastic methanogenesis instead
      of CO2 reduction.
AB  - Conductive materials/minerals can promote direct interspecies electron transfer
      (DIET) between syntrophic bacteria and methanogens in defined co-culture systems
      and artificial anaerobic digesters; however, little is known about the
      stimulation strategy of carbon material on methane production in natural
      environments. Herein, the effect of carbon cloth, as a representative of
      conductive carbon materials, on methane production with incubated wetland soil
      was investigated. Carbon cloth significantly promoted methanogenesis. With the
      application of electrochemical technology, calculation of the apparent electron
      transfer rate constant showed that carbon cloth significantly increased electron
      transfer rate (ETR) compared with the control experiment in presence of cotton
      cloth, from 0.0017 +/- 0.0003 to 0.0056 +/- 0.0015 s-1. Results obtained from
      both stable carbon isotope measurements and application of specific inhibitor
      (CH3F) for acetoclastic methanogenesis indicated that carbon cloth obviously
      promoted acetoclastic methanogenesis instead of CO2 reduction. High-throughput
      sequencing showed that methane production may stem from the involvement of
      Methanosarcina for both treatments. Our findings suggested that conductive carbon
      material can promote acetoclastic methanogenesis instead of CO2 reduction in a
      natural environment.

PMID- 30189520
TI  - Understand the resilience and regime shift of the wetland ecosystem after human
      disturbances.
AB  - Wetland protection and restoration are important for human's sustainable
      development, and assess the resilience and regime shift of wetland ecosystem
      under human disturbances is necessary for this purpose. Geochemical records,
      including nitrogen (N), phosphorus (P), heavy metals and polycyclic aromatic
      hydrocarbons (PAHs) from seven wetland cores dated by 210Pb and 137Cs analysis
      were used to identify the historical background of human disturbances on wetlands
      in the Sanjiang Plain. We also carried out paleoecological analysis (including
      plant macrofossils and diatoms) in one core (Honghe wetland) to reconstruct the
      successions of wetland ecological communities. The resilience and regime shift of
      ecosystem were evaluated based on autocorrelation and the Sequential t-test
      analysis of regime-shifts algorithm. Our results show that enrichment factors
      (EFs) of N, P and heavy metals (Cu, Zn, Pb etc.), and the concentrations of PAHs
      experienced slight increases from the 1920s but dramatic increases from the late
      1970s. The dominant species of plant community began to change from Drepanocladus
      aduncus to Carex lasiocarpa from the late 1970s, and the diatoms began to change
      from wet-indicator to dry-indicator species from the 1950s in Honghe wetland. The
      regime shift of the wetland ecosystem occurred around 1990 CE, which due to a
      drop in water level caused by human activities, such as wetland drainage for the
      reclamation and the excessive use of groundwater for irrigation purpose, rather
      than climate moisture variations. There is a time gap between the severe
      disturbances and regime shift due to the stronger resilience of wetland
      ecosystem. The ecological characteristics (e.g. water level, biological
      compositions, and EFs of nutrient elements and heavy metals) of Honghe wetland
      before the late 1970s (release phase) were used as reference conditions for
      wetland restoration.

PMID- 30189521
TI  - Air pollution: A public health approach for Portugal.
AB  - At the global level, several epidemiological studies have conclusively pointed
      out the associations between short-term exposure to air pollution and acute
      health effects, and long-term exposure with adverse health effects such as
      premature mortality from severe respiratory and cardiovascular diseases. This
      study intended to characterize exposures and their adverse health effects. Three
      independent sets of vectors were analyzed on a nationwide level and annual basis:
      air pollutant emissions, ambient air concentrations and health indicators of the
      period 2009 to 2015. The emissions analysis, for the studied pollutants, pointed
      out the main findings: (i) Lisbon Metropolitan Area presents the most problematic
      region with regard to the emissions of all the pollutants under study; (ii) the
      regions of the Alentejo and Algarve showed reduced emissions of the studied
      pollutants compared to other parts of the country; (iii) Northern regions PM10
      concentrations decreased during the two years in analysis. Regarding the analysis
      of air quality, it was concluded that: (i) regarding ozone, concentration shown a
      decreasing trend throughout the country; (ii) nitrogen dioxide and particulate
      matter, concentrations demonstrated an increasing trend in most of the northern
      part of the country; (iii) the regions of Alentejo and Lisbon Metropolitan Area
      showed increasing trends for sulfur dioxide and fine particles for the evaluated
      period. Decreasing trends in mortality associated with cardiovascular and
      respiratory causes are found mainly in the Alentejo and Algarve regions. In
      comparison, the North, Central regions, as well as, Lisbon Metropolitan Area
      exhibited higher mortality values related to this health indicators.

PMID- 30189522
TI  - Recent sediment flux to the Ganges-Brahmaputra-Meghna delta system.
AB  - The physical sustainability of deltaic environments is very much dependent on the
      volume of water and sediment coming from upstream and the way these fluxes
      recirculate within the delta system. Based on several past studies, the combined
      mean annual sediment load of the Ganges-Brahmaputra-Meghna (GBM) systems has
      previously been estimated to vary from 1.0 to 2.4 BT/year which can be separated
      into components flowing from the Ganges (260 to 680 MT/year) and Brahmaputra (390
      to 1160 MT/year). Due to very limited data and small contribution of the Meghna
      system (6-12 MT/year) to the total sediment flux of the GBM system, the data of
      the Meghna is not considered in the analysis assuming the sediment flux from GB
      system as the sediment flux of GBM. However, in this paper our analysis of
      sediment concentration data (1960-2008) collected by Bangladesh Water Development
      Board shows that the sediment flux is much lower: 150 to 590 MT/year for the
      Ganges versus 135 to 615 MT/year for the Brahmaputra, with an average total flux
      around 500 MT/year. Moreover, the new analysis provides a clear indication that
      the combined sediment flux delivered through these two major river systems is
      following a declining trend. In most of the planning documents in Bangladesh, the
      total sediment flux is assumed as a constant value of around 1 billion tons,
      while the present study indicates that the true value may be around 50% lower
      than this (with an average decreasing trend of around 10 MT/year).

PMID- 30189523
TI  - Impact of dosing order of the coagulant and flocculant on sludge dewatering
      performance during the conditioning process.
AB  - The combined use of coagulant and flocculant can achieve excellent dewatering
      performance. In this study, we investigated the impact of dosing order of the
      coagulant and flocculant on sludge dewatering performance. The results showed
      that capillary suction time (CST) values during the coagulation-flocculation
      process decreased 20-25% compared to those during the flocculation-coagulation
      process using the same doses of additives. Moisture content of the sludge during
      the coagulation-flocculation process was lower. The dosing order of coagulants
      and flocculants during the conditioning process was clearly important for sludge
      dewatering, and the coagulant should be dosed before the flocculant. Furthermore,
      a mechanism for the different dewatering performance was proposed: larger
      agglomerated and destabilized colloid particles formed, and more bound water was
      released into the sludge bulk solution during the coagulation-flocculation
      process, compared with the flocculation-coagulation process, which resulted in
      better dewatering performance, as reflected in the CST value and moisture content
      of the sludge cake. These results enable a better understanding of combined
      conditioning with coagulants and flocculants on sludge dewatering.

PMID- 30189524
TI  - Insight into a direct carbon dioxide effect on denitrification and denitrifying
      bacterial communities in estuarine sediment.
AB  - With the elevation of atmospheric CO2 content, the potential effects of CO2 on
      organisms and various environmental processes have gained increasing concern.
      Most previous studies on denitrification have been conducted on ecosystems
      comprising plants, soils and microbes, but they have ignored the direct effect of
      CO2 on denitrification and denitrifying bacterial communities. Here, by excluding
      the effects of plants, we found that both short- and long-term exposure to CO2
      directly inhibited the denitrification process, and caused the total nitrogen
      removal efficiency to decrease by up to 37%. Compared with the control, long-term
      exposure to CO2 (30,000 ppm) also caused >276-fold increase in N2O emissions, and
      significantly inhibited the decomposition process. Enzymatic and qPCR assays
      showed that CO2 decreased the denitrifying enzymes activity (DEA) and the copy
      numbers of denitrifying genes, which directly resulted in the inhibitory effect
      of CO2 on denitrification process. Further study indicated that adverse effect of
      CO2 on DEA and denitrifying genes were caused by reducing the relative abundance
      of denitrifying bacteria. Moreover, the relative abundance of fermenting bacteria
      also decreased as CO2 concentration increased, which might result in insufficient
      liable carbon for the activity of denitrifying bacteria, and ultimately
      exacerbate the negative denitrification performance. Overall, this study suggests
      that, in the absence of plants, CO2 could directly affect the denitrifying and
      fermenting bacterial community, and inhibit denitrification and decomposition
      processes, which is detrimental to sediment nitrogen and carbon cycles.

PMID- 30189525
TI  - A preliminary study on the role of suspended particulate matter in the
      bioavailability of oil-derived polycyclic aromatic hydrocarbons to oysters.
AB  - Suspended particulate matter (SPM) refers to fine-grained materials that are
      suspended in water columns. By providing a surface for the adsorption of non
      polar organic compounds, SPM is a carrier for persistent and toxic contaminants.
      A wide range of organic pollutants, including polycyclic aromatic hydrocarbons
      (PAHs), can be adsorbed onto SPM. The formation of particle-associated PAHs can
      sequentially increase the potential for exposure to and bioaccumulation by
      organisms. Until recently, most oil exposure studies were performed using freely
      dissolved and dispersed forms, and therefore the role of SPM in influencing the
      bioavailability and bioaccumulation of PAHs has not been considered. This study
      found that SPM influences the bioavailability of petrogenic PAHs in the water
      column and their potential for accumulation in oysters. SPM significantly
      enhanced the water column entrainment of petrogenic PAHs, thus increasing the
      potentials for uptake by exposed organisms. PAHs in the water column was highest
      from mechanically dispersed oil (MDO; 2.27 MUg/mL) >= oil-SPM aggregate (OSA;
      1.96 MUg/mL) > water accommodated fraction (WAF; 0.19 MUg/mL) but the percentage
      of PAHs accumulated in oysters were highest from WAF (18.3%) > MDO (14.2%) > OSA
      (9.62%). Despite the high water column available PAHs, oysters exposed to SPM
      associated oil accumulated PAHs at half the accumulation efficiency compared with
      those exposed to PAHs without SPM.

PMID- 30189527
TI  - Bioturbation by the razor clam (Sinonovacula constricta) on the microbial
      community and enzymatic activities in the sediment of an ecological aquaculture
      wastewater treatment system.
AB  - Bioturbation by the razor clam, Sinonovacula constricta, influenced the redox
      conditions and changed the sedimentary environment, providing a suitable micro
      environment for microbial growth. However, the mechanism of the integrated razor
      clam-microbial community in organic matter mineralization remains elusive. To
      study this mechanism, an in situ experiment was conducted to investigate the
      bioturbation effects of S. constricta on the microbial community and enzyme
      activities in the sediment of an ecological aquaculture wastewater treatment
      system. According to principal coordinate analysis (PCoA) and PERMANOVA, we found
      that the microbial community was significantly (P < 0.05) influenced by the
      bioturbation effect of S. constricta. Linear discriminant analysis effect size
      (LEfSe) showed that species involved in reduced effluent concentrations of TN and
      TP, such as Prolixibacteraceae, Nitrospira and Actinobacteria, were increased
      significantly (P < 0.05) by S. constricta. Molecular ecological network (MENs)
      analysis indicated that the bioturbation effect of S. constricta increased the
      complexity of interspecies interaction and changed the topological properties of
      individual OTUs. The results elucidated that S. constricta increased the
      microbial community network, as substantiated by a higher total number of nodes
      and a shorter geodesic distance. Zi < 2.5 and Pi <0.62 in MENs showed that the S.
      constricta treatment significantly increased (P < 0.05) the potential microbial
      community, with the keystone (OTU747049) Proteobacteria and (OTU74388)
      Bacteroidetes family Prolixibacteraceae, which connected different co-expressed
      OTUs. Furthermore, S. constricta significantly increased (P < 0.05) the enzymatic
      activities (alkaline phosphatase (APA), dehydrogenase and urease) of the
      substrate at different sampling depths. Overall, this study provides evidence
      that the bioturbation effect of S. constricta changes the microbial community
      structure, increases enzymatic activities and accelerates the degradation of
      organic matter in an aquaculture wastewater environment.

PMID- 30189526
TI  - Improving phosphorus removal in a surface flow wetland and land application
      system by geochemical augmentation with alum.
AB  - Constructed surface flow (SF) wetlands are commonly used for phosphorus (P)
      removal. Geochemistry of wetlands provides explicit mechanisms for permanent P
      sequestration in sediments. This study had two goals: (1) Find P removal
      performance and rate at the highest alum doses that do not produce floc in an SF
      wetland; and (2) Determine potential improvements to P removal performance with
      low alum doses in a 140-ha land application system downstream from the wetland.
      The study started with a small fraction of a conventional,
      flocculation/sedimentation alum dose, then progressively increased the dose to
      observe initiation of floc formation and removal of P. For flows near 10
      megaliters per day in an 0.8 ha SF wetland, doses started 189 L d-1 for two
      weeks, then increasing by 189 L d-1 every two weeks until the final two weeks at
      946 L d-1. At an alum dosing rate of 189 L d-1 (alum concentration of 9.5 mg L
      1), there was an order of magnitude improvement in P removal rates over
      literature values. Floc formation in the wetland was observed at 567 L d-1, but
      no significant improvement in P removal rates were observed until a conventional
      alum dose of 946 L d-1 was applied. Alum addition improved P removal performance
      in the land application system. In 2014, during which there was no alum dosing,
      the median effluent total P (TP) during the July-September dry season
      (groundwater dominated outflow) was 0.43 mg L-1. In 2015, (alum dosing August
      October) median dry weather TP of 0.18 mg L-1 was significantly lower (p <
      0.0001). Alum dosing in 2016 at 189 L d-1 produced a dry weather median of 0.28
      mg L-1, which was significantly lower (p = 0.015) than in the 2014 median. Mean
      daily dry weather TP loads to the land application system were 44 kg d-1 in 2014,
      45 kg d-1 in 2015, and 41 kg d-1 in 2016.

PMID- 30189528
TI  - Occurrence of C60 and related fullerenes in the Sava River under different
      hydrologic conditions.
AB  - The presence of nanomaterials in the environment has caught the attention of the
      scientific because of the uncertainties in their fate, mobility and potential
      toxic effects. However, few studies have determined experimentally their
      concentration levels in aquatic systems up to date, which complicates the
      development of an adequate risk assessment. In the present study, the occurrence
      of ten fullerenes has been assessed in the Sava River (Southeastern Europe): 27
      freshwater samples and 12 sediment samples from 12 sampling points have been
      analysed during two sampling campaigns. C60 was the most ubiquitous fullerene,
      with concentrations of 8 pg/l-59 ng/l and 108-895 pg/gdw in water and sediments,
      respectively. Statistically significant differences existed between the levels in
      2014 and 2015, which has been attributed to the extreme hydrologic conditions
      (severe floods and drought, respectively). C70 fullerene has been detected in
      most of the samples and the fullerene derivatives [6,6]-phenyl C61 butyric acid
      methyl ester and N-methyl fulleropyrrolidine have been detected eventually, which
      highlights that nanotechnology research and development activities are
      responsible for emitting these emerging contaminants to the environment. The role
      of diverse potential anthropogenic sources (including oil refinery, general
      industrial activity, river navigation, urban emissions and nanotechnology) is
      discussed.

PMID- 30189529
TI  - Yttrium and rare earth elements fractionation in salt marsh halophyte plants.
AB  - Salt marshes act as natural deposits of different metals (e.g. heavy-metals),
      while halophyte plants are known to retain and accumulate them in the different
      tissues. Scarce data exists on accumulation, partition and fractionation of YREE
      in these plants. To study the relationship between halophyte plants and YREE,
      contents of these metals were determined by ICP-MS in sediment, and in the
      different plants organs, from Rosario's salt marsh, in Tagus estuary (SW Europe).
      Results show significant differences (p < 0.001) in YREE contents between
      sediments. In non-colonised sediment Y was lower (5.0-18 mg.kg-1) compared to the
      Sarcocornia fruticosa and Spartina maritima sediment cores (19-26 and 20-26 mg.kg
      1, respectively). The same was observed for SigmaREE, with lower values in non
      colonised sediment (32-138 mg.kg-1), while colonised ones presented higher
      contents (146-174 and 151-190 mg.kg-1, for S. fruticosa and S. maritima,
      respectively). These significant differences (p < 0.05) are explained by the
      sediments' nature. Yttrium and SigmaREE Al-normalised ratios in non-colonised
      sediment ranged from 1.5 to 2.3 and 11 to 13, respectively. The colonised
      sediments revealed significant higher ratios (particularly for SigmaREE/Al
      ratios; p < 0.001), varying from Y/Al: 1.8-2.3 and SigmaREE: 13-16 for S.
      fruticosa, and Y/Al: 1.4-2.3 and SigmaREE: 12-18, for S. maritima. Results
      suggest that these plants may promote YREE enrichment in the sediments. No
      differences in fractionation patterns among sediments and in both species roots
      were found, but fractionation was different from those in the sediment, with
      similar middle-REE (MREE) enrichment and no light-REE (LREE) and heavy-REE (HREE)
      fractionation. No evidence of YREE transfer to aboveground organs was observed.
      Different fractionation patterns in stems and leaves were registered, with clear
      enrichment of LREE relative to HREE and an increase in the MREE enrichment.
      Therefore, these plants showed low ability to accumulate and translocate YREE but
      may promote its enrichment in the sediments.

PMID- 30189530
TI  - Comparing anthropogenic heat input and heat accumulation in the subsurface of
      Osaka, Japan.
AB  - In metropolitan areas, shallow groundwater temperatures are affected by
      anthropogenic heat sources. The resulting thermal conditions in the subsurface
      are highly site-specific, and spatial and temporal trends have only been revealed
      for a few cities. In this study, the anthropogenic heat input is quantified for
      15 locations in Osaka, Japan using an analytical, one-dimensional conductive heat
      transport model. Mean anthropogenic fluxes into the subsurface are determined
      annually between 2003 and 2011. The model depicts fluxes from buildings and from
      different land cover types separately. The main objective is to compare the
      predicted annual mean heat input to heat storage increase, and to identify site
      specific factors relevant for the thermal evolution of the underground at each
      well location. Our results indicate that mean fluxes from asphalt covered areas
      (0.28 +/- 0.07 W/m2) and from buildings (0.32 +/- 0.18 W/m2) are significantly
      higher than fluxes from unpaved (0.06 +/- 0.06 W/m2) and grass-covered (-0.04 +/-
      0.06 W/m2) areas. Furthermore, the temporal variation of mean fluxes from
      buildings is stable over the studied time period, while annual mean fluxes from
      asphalt, grass and unpaved areas vary as much as 0.8 MJ/m2. Still, the
      uncertainty associated with the combined annual heat input of all heat sources is
      slightly higher than the changes between the years. Overall, the predicted
      cumulative heat input (2003 to 2011) at the wells ranges from 4 MJ/m2 to 60
      MJ/m2. Comparing these results to heat storage increase, additional local heat
      fluxes, such as from construction work or a sewage treatment plant, have to be
      considered for about 1/3 of the wells. In addition, it becomes apparent that a
      significant percentage of determined anthropogenic heat input is not stored in
      the urban aquifer and heat input is predicted to be considerably higher than heat
      storage increase.

PMID- 30189531
TI  - Temporal (1970-2016) changes in human pressures and wetland response in the St.
      Lawrence River (Quebec, Canada).
AB  - Temporal changes (1970-2016) in St. Lawrence River wetlands were assessed between
      Cornwall and Quebec (~400 km) to assess wetland response to cumulative
      anthropogenic pressures in the watershed. Emergent wetlands area and biomass of
      submerged aquatic vegetation (SAV) were contrasted among five regions subjected
      to sharply different water level/discharge regime (stabilized, semi-natural,
      tidal), nutrient concentrations and shoreline use (rural to urbanized). Between
      1970 and 2016, over the growing season (April-Sept.), St. Lawrence River mean
      water level at Sorel dropped by ~1 m and mean water temperature increased by ~3 
      degrees C. Reductions in phosphorus concentrations (by ~2-fold) were observed
      over time both in water and in SAV tissues, in phase with improvements of urban
      wastewater treatment and P-reduction in upstream Lake Ontario. Nitrate
      concentrations in water increased and SAV biomass decreased between the 1970s and
      2008 in the downstream regions of Lake Saint-Pierre and fluvial corridor
      subjected to the cumulative impacts from urban centers and intensively farmed
      watersheds. Over the 1970-2010 period, dropping water levels yielded slightly
      increasing wetland areas, owing to the downslope colonization of emergent and
      submerged plants. In urbanized regions, emergent wetlands shifted towards drier
      assemblages dominated by invasive reed species. Encroachment of wetlands by
      agriculture accounted for most wetland losses in rural Lake Saint-Pierre, which
      holds the single largest area (197 km2) of continuous wetland habitat of the
      entire watershed. Our results highlight the strong response of riverine wetlands
      to a wide range of human pressures, including dropping water levels, changing
      nutrient concentrations, rising population and intensifying agriculture.

PMID- 30189532
TI  - Water replenishment for ecological flow with an improved water resources
      allocation model.
AB  - With rapid urbanization, there will be more conflict between human systems and
      the river ecological system, and therefore, ecological operations, practices and
      research must involve the ecological water replenishment of entire river basins
      with new modeling tools. In this study, based on a water resource allocation and
      simulation model (WAS), we establish an ecological flow-oriented water resource
      allocation and simulation framework (E-WAS) by comprehensively considering both
      ecological flow constraints and ecological flow targets. To control multiple
      types of water sources and dynamically allocate water resources to replenish
      ecological water in the river, virtual reservoirs and ecological units are added
      to the model network. With new water balance equations for virtual reservoirs and
      ecological units, the E-WAS can simulate the ecological replenishment process in
      a river basin and can provide a recommended water replenishment scheme that
      considers optimization principles. The E-WAS was applied in the Pingshan River
      Basin, Shenzhen, China. Fourteen ecological units and 38 water supply nodes are
      considered in the model. A water replenishment scheme that used water from 6
      reservoirs and reclaimed water from 5 water sewage plants was selected. This
      scheme significantly increased the satisfactory degree of ecological water demand
      and efficiently supported the formulation of a control scheme for the water
      environment of a basin. The E-WAS framework is similar to model plug-ins but
      helps to avoid the large workload that is required for model redevelopment and
      can expand the functions of core models relatively quickly.

PMID- 30189533
TI  - Effect partition of climate and catchment changes on runoff variation at the
      headwater region of the Yellow River based on the Budyko complementary
      relationship.
AB  - The headwater region of the Yellow River (HRYR) is one of the most important
      water supply areas of the whole river basin, which has suffered a serious water
      shortage problem for recent years. A better understanding of impacts of climate
      and catchment changes on runoff variation will help to determine efficient
      measures to deal with the runoff reduction in the Yellow River. The Budyko
      complementary relationship between the partial elasticity of runoff (R) with
      respect to precipitation (P) and that with potential evapotranspiration (E0) was
      used in this study to partition the effects of climate and catchment changes on
      runoff variation at the HRYR. The upper and lower bounds of the contributions of
      climate and catchment changes to runoff variation were determined for every five
      years during 1961-2010. Results show that the complementary relation method based
      on the Budyko hypothesis can partition the contributions of climate and catchment
      changes to runoff variation effectively. And the climate changes are the main
      reasons (account for 60%-70% of the runoff variation) for runoff reduction at the
      HRYR. The sensitivity coefficient of R with respect to P has a significant
      decreasing trend at the 0.05 level with arid ratio (E0/P) and that with respect
      to E0 has a significant increasing trend at the 0.05 level with E0/P, indicating
      that with drying climate, R becomes more insensitive to climate changes. More
      precipitation is consumed by evapotranspiration returning to the atmosphere,
      leading to the runoff reduction at the HRYR.

PMID- 30189534
TI  - Multiple-life-stage probabilistic risk assessment for the exposure of Chinese
      population to PBDEs and risk managements.
AB  - Studies assessing body burden of polybrominated diphenyl ethers (PBDEs) exposure
      have been conducted in the United States and Europe. However, the long-term
      assessment that is associated with multimedia exposure of PBDEs for the Chinese
      population is not available. The current study estimated the health risks using
      large PBDEs data to quantify the contributions of various media from different
      regions and distinguished the most vulnerable periods in life. We summarized
      media-specific (soil, dust, outdoor and indoor air, human milk and food)
      concentration of PBDEs in China from 2005 to 2016. Probabilistic risk assessment
      was adopted to estimate the health risks of infants, toddlers, children,
      teenagers and adults through ingestion, inhalation and dermal absorption. Monte
      Carlo simulation and sensitivity analysis were performed to quantify risk
      estimates uncertainties. E-waste areas had the highest PBDEs concentration, which
      was at least an order of magnitude higher than in other areas. BDE209 was the
      primary congener, accounting for 38-99% of the estimated daily intake. The
      dominant exposure pathway for infants was dietary intake through human milk,
      whereas dust ingestion was a higher contributing factor for toddlers, children,
      teenagers and adults. The 95th percentile of hazard index for infants and
      toddlers from e-waste areas of Guangdong and Zhejiang provinces exceeded one. Our
      estimates also suggested that infants may have the highest body burdens of PBDEs
      compared to other age groups. Sensitivity analyses indicated that PBDEs
      concentrations and ingestion rates contributed to major variances in the risk
      model. In this study, e-waste was found as a significant source of PBDEs, and
      PBDEs-containing e-waste are likely to be a threat to human health especially
      during early period of life. Risk strategies for better managing environmental
      PBDEs-exposure and human health are needed, due to the high intake of PBDEs and
      their persistence in the environment.

PMID- 30189535
TI  - Behaviour and fate of vanadium during the aerobic neutralisation of hyperalkaline
      slag leachate.
AB  - Vanadium is a toxic metal present in alkaline leachates produced during the
      weathering of steel slags. Slag leaching can therefore have deleterious effects
      on local watercourses due to metal toxicity, the effects of the high pH (9-12.5)
      and rapid carbonation (leading to smothering of benthic communities). We studied
      the fate and behaviour of V in slag leachate both through field observations of a
      heavily affected stream (Howden Burn, Consett UK) and in controlled laboratory
      experiments where slag leachates were neutralised by CO2 ingassing from air. V
      was found to be removed from leachates downstream from the Howden Burn source
      contemporaneously with a fall in pH, Ca, Al and Fe concentrations. In the
      neutralisation experiments pH reduced from 12 -> 8, and limited quantities of V
      were incorporated into precipitated CaCO3. The presence of kaolinite clay (i.e.
      SiOH and AlOH surfaces) during neutralisation experiments had no measureable
      effect on V uptake in the alkaline to circumneutral pH range. XANES analysis
      showed that V was present in precipitates recovered from experiments as adsorbed
      or incorporated V(V) indicating its likely presence in leachates as the vanadate
      oxyanion (HVO42-). Nano-scale particles of 2-line ferrihydrite also formed in the
      neutralised leachates potentially providing an additional sorption surface for V
      uptake. Indeed, removal of V from leachates was significantly enhanced by the
      addition of goethite (i.e. FeOOH surfaces) to experiments. EXAFS analysis of
      recovered goethite samples showed HVO42- was adsorbed by the formation of strong
      inner-sphere complexes, facilitating V removal from solution at pH < 10. Results
      show that carbonate formation leads to V removal from leachates during leachate
      neutralisation, and the presence of both naturally occurring and neoformed Fe
      (oxy)hydroxides provide a potent sink for V in slag leachates, preventing the
      spread of V in the environment.

PMID- 30189536
TI  - Do the pristine physico-chemical properties of silver and gold nanoparticles
      influence uptake and molecular effects on Gammarus fossarum (Crustacea
      Amphipoda)?
AB  - The specific and unique properties of silver nanoparticles (AgNPs) and gold
      nanoparticles (AuNPs), make them of high interest for different scientific and
      industrial applications. Their increasing use will inevitably lead to their
      release in the environment and aquatic ecosystems where they may represent a
      threat to aquatic organisms. Being a widespread and important component of the
      aquatic macroinvertebrate assemblage, amphipods and more specifically Gammarus
      fossarum will certainly be exposed to AgNPs and AuNPs. For these reasons, G.
      fossarum was selected as model organism for this study. The aim of the present
      work was the evaluation of the influence of both size (20, 40 and 80 nm) and
      surface coating (citrate CIT, polyethylene glycol PEG) on the acute toxicity of
      AgNPs and AuNPs on G. fossarum. We investigated the effects of AgNPs and AuNPs on
      the uptake by G. fossarum, NP tissue distribution and the expression of stress
      related genes by the use of ICP-MS, NanoSIMS50, Cytoviva(r), and Rt-qPCR,
      respectively. Ag and Au bioaccumulation revealed a significant surface-coating
      dependence, with CIT-AgNPs and CIT-AuNPs showing the higher bio-accumulation
      potential in G. fossarum as compared to PEG-NPs. Opposite to that, no size
      dependent effects on the bioaccumulation potential was observed. SIMS imaging and
      CytoViva(r) revealed an influence of the type of metal on the tissue distribution
      after uptake, with AgNPs detected in the cuticle and the gills of G. fossarum,
      while AuNPs were detected in the gut area. Furthermore, AgNPs were found to up
      regulate CuZnSOD gene expression while AuNPs led to its down-regulation.
      Modulation of SOD may indicate generation of reactive species of oxygen and a
      possible activation of antioxidant defence in order to prevent and defend the
      organism from oxidative stress. However, further investigations are still needed
      to better define the mechanisms underlying the observed AgNPs and AuNPs effects.

PMID- 30189537
TI  - Long-term exposure to ambient air pollution and autism spectrum disorder in
      children: A case-control study in Tehran, Iran.
AB  - Some recent human and animal studies have suggested that air pollution may affect
      the central nervous system and contribute to neurodevelopmental outcomes, such as
      autism spectrum disorder (ASD). We aimed to investigate the association between
      long-term exposure to ambient air pollution and increased odds of ASD among 2 to
      10-year-old children. We conducted a case-control study in Tehran, Iran. Cases
      were 134 children born between 2004 and 2012 diagnosed with ASD whose mothers
      were resident in Tehran during their pregnancy, and controls were 388 children
      without ASD randomly selected from public schools and kindergartens. Land-use
      regression models were used to estimate their annual mean exposure to ambient
      particulate matter with aerodynamic diameter <=10 MUm (PM10), sulfur dioxide
      (SO2), benzene, toluene, ethylbenzene, p-xylene, o-xylene, m-xylene (BTEX), and
      total BTEX. Logistic regression was used for the analyses and adjusted for
      possible confounding variables. The odds ratios per 1 unit increase in pollutants
      in the adjusted models were 1.00 (95% CI: 0.99, 1.01) for PM10, 0.99 (95% CI:
      0.99, 1.00) for SO2, 0.96 (0.83, 1.11) for benzene, 1.00 (0.96, 1.04) for
      toluene, 0.95 (0.79, 1.16) for ethylbenzene, 1.00 (0.78, 1.27) for p-xylene, 1.09
      (0.94, 1.27) for o-xylene, 1.01 (0.92, 1.12) for m-xylene, and 0.99 (0.97, 1.01)
      for total BTEX. We did not find the evidence of association between estimated
      annual mean exposure to abovementioned ambient air pollutants and increased odds
      of ASD in children. However, our findings might be due to some important
      limitations. Further research with better control of confounding variables,
      improved spatiotemporal exposure estimates, and inclusion of other important
      markers of air pollution is recommended.

PMID- 30189538
TI  - Involving victim population in environmentally sustainable strategies: An
      analysis for post-conflict Colombia.
AB  - Environmental objectives tend to receive a push to the background in post
      conflict scenarios. On the other hand, the processes displacement and refugee's
      relocation in post-conflict countries have been associated with different
      environmental impacts. Currently, Colombia faces a post-conflict scenario, which
      brings about relevant socio-environmental challenges: it is a mega-biodiverse
      country, it has millions of displaced people and is one of the most inequitable
      country in the world. Since there is a gap in post-conflict studies regarding the
      exploration of victims' involvement in environmental strategies, this paper aims
      to analyze victims' willingness to participate (WP) in Land Recovery Strategies
      (LRS) in post-conflict Colombia. This research (1) describes the socio-economic
      characteristics of forced-displacement victims from a Caribbean municipality of
      Colombia; (2) analyzes the victims' WP in hypothetical LRS and their preferred
      type of participation in the project, (3) identifies the way of grouping victims
      according their WP. Finally, (4) it analyzes the kind of benefits victims would
      prefer to receive in exchange for their participation in the LRS. Our results
      made evident that the majority of the consulted victims are willing to
      participate in LRS by giving up manual work time or in exchange of local
      ecological knowledge. We also found that the victims' participation in LRS
      associates to the age of the respondents, and whether they have benefited from
      government programs previously. Victims would prefer monetary retribution in
      exchange for their involvement in LRS, which may be explained by their vulnerable
      socioeconomic conditions. This research also demonstrates that victims with
      positive WP in LRS are a heterogeneous group. We highlight the need of actively
      involving women in LRS and other post-conflict projects in order to ensure their
      wellbeing. The results of this research are valuable, because they put forward
      the population of victims as an active performer within environmental
      sustainability.

PMID- 30189539
TI  - Nutrient addition increases the capacity for division of labor and the benefits
      of clonal integration in an invasive plant.
AB  - Many of the most invasive plants are clonal, and clonal integration has been
      proposed as an important mechanism promoting invasiveness. When the
      availabilities of two essential resources are negatively correlated in space,
      clonal integration may benefit clonal plants through division of labor. We
      hypothesized that environments with reciprocal patchiness of light and soil water
      may induce division of labor, and nutrient addition may increase both the
      division of labor and the benefits of clonal integration. To test this, we grew
      pairs of connected and disconnected ramets of the clonal invader Mikania
      micrantha under negative spatial covariance of light and soil water such that the
      proximal ramets were grown under high light and low soil water conditions and the
      distal ramets were grown under low light and high soil water conditions. In half
      of the ramet pairs, both ramets of a pair received a nutrient addition treatment.
      The results showed that connection decreased the root to shoot ratio in proximal
      ramets and increased it in distal ramets, indicating that division of labor was
      induced. In addition, connection increased the root to shoot ratio of distal
      ramets more under high soil nutrient conditions than under low soil nutrient
      conditions, indicating that nutrient addition increased the division of labor.
      Connection increased plant biomass at the whole clonal fragment level, and this
      increase was larger under high soil nutrient conditions than under low soil
      nutrient conditions. This study showed, for the first time, that in environments
      with reciprocal patchiness of two essential resources, the capacity for division
      of labor and its influence on plant performance may depend on the availability of
      a third essential resource. Because invasive plants often can acquire a larger
      amount of soil resources than native plants, our study may also contribute to the
      understanding why clonality is related to invasiveness.

PMID- 30189540
TI  - Reduction of persistent and semi-persistent organic pollutants in fillets of
      farmed European seabass (Dicentrarchus labrax) fed low fish oil diets.
AB  - Traditionally, a major part of aquaculture technology requires fish oil (FO) and
      fish meal (FM) to produce the aquafeed for farmed species. FO is the main source
      of persistent organic pollutants (POPs) in fish feed. In recent years, the use of
      vegetable-origin ingredients in fish feeds has been increasingly studied as an
      alternative to reduce the levels of these lipophilic pollutants in farmed
      species. The aim of this study was to evaluate the effect of the use of dietary
      vegetable oils in the farming of European sea bass (Dicentrarchus labrax) on the
      contents in persistent - polychlorinated biphenyls (PCBs) and organochlorine
      pesticides (OCPs) - and semi persistent pollutants - polycyclic aromatic
      hydrocarbons (PAHs) and polybrominated diphenyl ethers (BDEs) - of their edible
      parts. A total of 60 seabass muscle pools were obtained from fish farmed
      employing six experimental diets, which contained different percentages of FO (6
      vs. 3%) and FM (20%, 10% and 5%). We did not observe differences in the
      contamination level of seabass muscle in relation to the percentage of FM in
      their diet. However, the fish farmed using feed which had lower levels of FO (3%)
      showed significantly lower muscle levels of SigmaPCBs and carcinogenic PAHs
      (Sigmac-PAHs), with a reduction of 25.6% and 95.11% (respectively), as compared
      with those fished raised with feed with higher levels of FO (6%). Also much lower
      levels were found in OCPs such as sum of DDTs (30.88% of reduction), sum of
      chlordanes (42.85% of reduction), and sum of BDEs (48.16% of reduction) in those
      seabass fed with a lower percentage of FO. The results of this study indicate
      that the use of alternative feed ingredients that allow the employment of low
      percentage of FO in feeds help to reduce the load of several toxic pollutants in
      the fillets of European seabass.

PMID- 30189541
TI  - Dasymetric mapping of urban population in China based on radiance corrected DMSP
      OLS nighttime light and land cover data.
AB  - High spatial resolution urban population dataset is increasingly required for
      sustainable urban planning and management. Dasymetric mapping is an effective
      approach to create such dataset. However, the created gridded total population
      datasets usually have limitation for urban analysis in developing countries as
      they usually underestimate urban population because of the strong urban-rural
      difference. In this study, we aimed to create a dataset of gridded urban
      population with 1 km resolution in China in year 2000 and 2010. We proposed an
      index of urban nighttime light (UNTL) by integrating radiance corrected DMSP
      nighttime light (RcNTL) and urban land, which is then used as weight to
      disaggregate county-level urban population. The validation using township
      population in Beijing as references shows reasonable accuracy with a mean
      relative error of 38% and a R2 of 68%. Using only two widely available datasets
      (RcNTL and urban land), the proposed method is simple and computing efficient
      compared with methods using multiple geospatial data (e.g., land use and land
      cover, distance to city center, slope) and that combined with remote sensing
      imagery. As the used two auxiliary datasets are accessible globally, the method
      has great potential to produce similar urban population dataset for other
      developing countries where fine scale census population datasets are scarce. The
      produced urban population dataset is valuable for enriching our understanding of
      the urbanization process and designing sustainable urban planning and management
      strategies in China.

PMID- 30189542
TI  - Anthropogenic particles in the stomach contents and liver of the freshwater fish
      Squalius cephalus.
AB  - Anthropogenic particles (APs) are a very broad category of particles produced
      directly or indirectly by human activities. Their ingestion by biota is well
      studied in the marine environment. In contrast, studies on AP ingestion in wild
      freshwater organisms are scarce despite high contamination levels in some rivers
      and lakes. In this study, we aimed to evaluate the ingestion of APs and the
      possible occurrence of APs in the liver and muscle of a freshwater fish, Squalius
      cephalus, from the Parisian conurbation. After isolation, the particles were
      analyzed using Raman spectroscopy. In sixty stomachs, eighteen APs were found,
      half of which were plastics and the other half were dyed particles. Twenty-five
      percent of sampled individuals had ingested at least one AP. The mean length of
      the APs was 2.41 mm. No significant difference was found between the sites
      upstream and downstream of Paris. Additionally, 5% of sampled livers contained
      one or more APs, which were characterized as microplastics (MPs). No APs were
      found in the muscle tissue. The majority of APs isolated from stomach contents
      were fibers, which is similar to the findings of a previous river contamination
      study. This highlights that fish could be more exposed to fibers than previously
      thought and that more studies on the impacts of fiber ingestion are required.
      Despite their low occurrence, MPs are reported, for the first time, in the liver
      of a wild freshwater fish species. While the pathways and impacts are still
      unknown, MPs also occur in liver of marine mollusks and fish. Physiological in
      vitro studies are needed to better evaluate the impacts of such phenomena.

PMID- 30189543
TI  - Toxicological responses of surfactant functionalized selenium nanoparticles: A
      quantitative multi-assay approach.
AB  - The utilization of selenium nanomaterials (Se Nps) in material and biological
      science is quickly growing, crafting an imperative need for toxicological
      evaluation of the exposure prospective and environmental consequences of Se Nps.
      The combination of quantitative multi-assay approach into environmental
      toxicological analysis has provided novel opportunities to build up effective
      markers and scrutinize the means of venomous nature of Se Nps in the current
      study. In the present work, we analyzed the toxicological effect of bare and
      surface functionalized Se Nps by using multi assay viz. seed germination studies
      as a function of concentration of SeNps and by using antifungal assays. The
      influence of SeNps on bacterial activities were also investigated by using the S.
      aureus, E. coli, P. aeruginosa and S. typhi bacterial strains as widespread
      marker species for antibacterial studies. The ocular assessment of chlorophyll
      content was maximum for Brij coated Se NPs (98%) as compared to bare (20%), SDS
      (45%) and CTAB (38%) coated SeNps. The existence of chromosomal aberrations in
      root meristems of A. cepa(A. cepa) with computed MI values of 16, 25, 33 and 52%
      for bare, CTAB, SDS and Brij coated particles has indicated the genotoxic effects
      of SeNps. The biocompatible nature of Brij coated Se Nps was observed from the
      faster mobility of DNA in gel electrophoresis studies. The investigational
      studies in the current work appraise the toxicity and measure the competence of
      obtained data to characterize possibilities of probable threats, prominence of
      data requirement and breaches that must be filled to diminish the ambiguities
      about the safe use of Se Nps.

PMID- 30189544
TI  - Impact of O-alkyl-pyridineamidoximes on the soil environment.
AB  - Pyridine derivatives such as oximes and amidoximes are widely used in
      pharmaceutical, analytical and coordination chemistry. Increasing interest in
      this group of compounds as well as their complexing properties and surface
      activity resulted in their introduction into the environment and change of the
      ecosystem functioning. Based on this phenomenon, the evaluation of impact O-alkyl
      pyridineamidoximes on the soil environment was determined by analysis of changes
      of metal mobility in soil and plant seed germination. The obtained results
      indicate that O-propyl-pyridineamidoximes may change the mobility of metals in
      soil and influence the germination and development of plants. The introduction of
      these compounds to soil resulted in the reduction of metal (Cu, Pb, Fe) mobility
      in the soil matrix. This effect resulted in the retention of metals in the soil
      and inhibition of their mobility. This phenomenon suggests the possibility of
      using the analyzed compounds in the remediation process as a stabilizing factor.
      Pyridineamidoximes at a concentration below 100 mg/kg of soil did not influence
      the seed germination and plant development.

PMID- 30189545
TI  - Determination of real-world emission factors of trace metals, EC, OC, BTEX, and
      semivolatile organic compounds (PAHs, PCBs and PCNs) in a rural tunnel in
      Bilecik, Turkey.
AB  - A field study was performed in a rural tunnel to determine pollutant
      concentrations, sources and on road vehicle emission factors (EFs) of particulate
      matter, trace metals, elemental carbon (EC), organic carbon (OC), benzene,
      toluene, ethyl benzene and xylenes (BTEX), and polycyclic aromatic hydrocarbons
      (PAHs). Emission factors (EFs) for polychlorinated naphthalenes (PCNs) and
      polychlorinated biphenyls (PCBs) were also determined. A 12-day extensive
      sampling campaign during morning and afternoon periods at inlet and exit stations
      of the tunnel was conducted. Morphology of the particles was also investigated by
      Scanning Electron Microcopy (SEM). Correlation analysis, factor analysis and
      diagnostic PAH ratios were utilized to identify emission sources of trace metals.
      Identified sources include brake wear (33%), resuspension of road dust (15%),
      tyre wear (12%), exhaust emissions (10%), and lubricants (9%). Based on the PAH
      diagnostic ratios, major sources of PAHs were estimated as diesel emissions. EFs
      were comparable with the literature and varied from 31.5 to 295.4 mg vehicle-1 km
      1 with an average of 129.2 +/- 80 mg vehicle-1 km-1 for PM2.5. PM2.5-10 EFs
      varied between 15.9 and 236.1 mg vehicle-1 km-1 with an average of 96 +/- 30 mg
      vehicle-1 km-1. Average EC EFs were 40.3 +/- 9.8 mg vehicle-1 km-1 for PM2.5
      samples and 19.5 +/- 0.5 mg vehicle-1 km-1 for PM2.5-10 samples while OC EFs were
      33.7 +/- 18 and 15.5 +/- 8.4 mg vehicle-1 km-1 for fine and coarse particles,
      respectively. EFs of elements were generally 2 (Al) to 59 (Mg) times higher than
      those previously reported in the literature. Compared to literature, relatively
      higher EFs for Sigma13PAHs (range: 48.1-168 MUg vehicle-1 km-1, average: 84.3 +/-
      46.4 MUg vehicle-1 km-1) were obtained. BTEX emission factors were in the range
      of 4.2 +/- 4.7 mg vehicle-1 km-1 (m + p-xylene) and 16.7 +/- 10.5 mg vehicle-1 km
      1 (toluene). Average EFs for SigmaPCBs and SigmaPCNs were 12.06 +/- 5.3 MUg
      vehicle-1 km-1 and 88.9 +/- 70.4 ng vehicle-1 km-1, respectively.

PMID- 30189546
TI  - Establishment of geochemical background and threshold values for 8 potential
      toxic elements in the Bulgarian soil quality monitoring network.
AB  - Establishment of geochemical background and threshold values of potentially toxic
      elements is essential for soil management activities. Available topsoil data
      collected in the Bulgarian soil quality monitoring network are explored for the
      concentrations of the potentially toxic elements (PTEs) of As, Cd, Cr, Cu, Hg,
      Ni, Pb and Zn. The 'median + 2MAD' and TIF methods for obtaining geochemical
      threshold values, which differentiate sampling sites with background from those
      with unusually high element concentrations, are presented. Comparison of the
      derived national geochemical threshold values with those obtained in European
      studies outlines the specificity of the Bulgarian PTE background concentrations
      among the other southern European countries. The threshold values for Cd, Cu, Ni,
      Pb and Zn are more similar to those derived from the northern European countries
      since the As and Cr ones are more close to the values derived for southern
      Europe. The geochemical threshold of Hg is almost one order of magnitude as high
      as the southern European derived value. The usage of geochemical threshold values
      for soil risk assessment is suggested by comparison with soil quality guideline
      values adopted in other countries. The combination of threshold values based on
      90th percentile with geochemical mapping identifies the priority areas for
      further assessment. Regions with more than 2 PTEs (2.26% of the Bulgarian
      territory) are suggested for detailed (eco)toxicological assessment.

PMID- 30189547
TI  - Elevated nutrient concentrations in headwaters affected by drained peatland.
AB  - Nutrient export from drained peatland has significant impacts on aquatic
      environments in Nordic catchments. Spatial information on variations in nutrient
      concentrations across different landscapes and land uses is needed to design
      measures for achieving the good ecological status of the EU Water Framework
      Directive. In this study we determined background concentrations in natural
      peatland-dominated streams and examined effects of peatland use practices on
      water quality in headwater catchments. We quantified sources for different
      elements by joint analysis of water chemistry, isotopes, and hydrology for 62
      small catchments in North Ostrobothnia, Finland. Concentrations of nutrients and
      suspended solids were relatively high in catchments containing drained peatland.
      In particular, dissolved nitrogen and phosphorus concentrations were elevated
      during baseflow conditions when flow likely originated from deeper soil layers.
      Total concentrations of nutrients, suspended solids, and loss on ignition also
      showed elevated values, and changes in the ratio of dissolved and particulate
      forms, especially the C/N ratio, were observed. Past drainage had a stronger
      effect on organic matter and nutrients concentrations than local hydroclimate
      conditions. These results strongly indicate that current water protection methods
      are not sufficient to capture all seasonal variations in nutrient and suspended
      solid loads from drained peatland. Thus, more effort and actions are needed for
      water protection in such areas.

PMID- 30189548
TI  - Variations in grain cadmium and arsenic concentrations and screening for stable
      low-accumulating rice cultivars from multi-environment trials.
AB  - In order to help mitigate widespread cadmium (Cd) and arsenic (As) co
      contamination in paddy soils in China, screening and breeding of low-accumulating
      rice (Oryza sativa L.) cultivars (excluders) have been widely adopted. However,
      the performance of rice cultivars for grain Cd and As accumulation may vary in
      different growing environments. The inability to identify stable low-accumulating
      cultivars has largely hindered their application. In this study, 51 rice
      cultivars were evaluated at four Cd- and As-contaminated paddy sites in two crop
      seasons in northern Guangdong Province, China. The aim was to investigate the
      effects of cultivar, environment and their interactions in determining grain Cd
      and As concentrations, and so to identify stable low-accumulating cultivars.
      Results showed that environment effects dominated the Cd and As concentrations in
      rice grains, explaining 87% of the total variations. The crop season played a
      vital role; compared to early season, grain Cd levels increased and As levels
      lowered significantly in late season. Large variations in grain Cd, total As,
      inorganic As concentrations and the percentage of inorganic As were observed
      between different cultivars. Conventional japonica cultivars exhibited lower Cd
      levels but higher As levels in the grains than did indica cultivars. The cultivar
      * environment interaction (CEI) was significant, and its importance was
      comparable to the cultivar effect. By measuring and interpreting such an
      interaction, stable Cd and As excluder cultivars were identified based upon the
      yield, grain Cd and As levels as well as the stabilities of cultivars across the
      trial environments. Two stable Cd and As co-excluders were found among the hybrid
      indica cultivars. These results demonstrated that the variations in grain Cd and
      As concentrations could mainly be attributed to the environment effects and
      cultivar selection practices should include the analysis of CEI to identify
      stable low-accumulating rice cultivars.

PMID- 30189550
TI  - Ecosystem Services in Life Cycle Assessment: A novel conceptual framework for
      soil.
AB  - Ecosystem Services (ES) are the direct and indirect contributions of ecosystems
      to human well-being, which include provision of food and water, regulation of
      flood and erosion processes, soil formation and non-material benefits such as
      recreation. The integration of ES impact modeling in Life Cycle Assessment (LCA)
      still has limitations regarding the typology embodied and some conceptual errors
      in not actually evaluating the benefits provided by ES. In this context, soil is
      an important resource and provides a wide diversity of ES. Therefore, this
      article aims to: (i) Review the evolution of ES assessment in LCA and the current
      methods used to study the biophysical aspects of ES; (ii) Compare the ES cascade
      model and LCA environmental mechanism for land use impacts; and (iii) Improve and
      synthesize a new conceptual framework for soil-ES assessment in LCA studies.
      Results show that the cascade model provides a useful framework for
      operationalizing ES assessment and should integrate LCA. Thus, this study
      proposes a new conceptual framework for soil-ES including the main soil
      processes, functions, services, benefits and values. Each of these cascade model
      steps is aligned with LCA terminology in order to match the usual midpoint or
      endpoint levels of modeling. Future works should focus on new indicators to
      measure the supply of ES and their benefit to humans as well as indicators to
      their value.

PMID- 30189549
TI  - Silver nanomaterials in the natural environment: An overview of their
      biosynthesis and kinetic behavior.
AB  - Silver nanomaterials (Ag NMs) are fabricated by many biological components in our
      environment. Recently, research on their biosynthesis and reactions has become a
      focus of attention. Due to the complexity of biological systems and samples,
      specific processes and mechanisms involving Ag NMs are difficult to identify and
      elucidate on the molecular and chemical-bond level. The microorganisms and
      composite components of plant extracts are of great interest in many biological
      syntheses. Although potential biomolecules have been shown to play essential
      roles in biological systems in Ag NM biosynthesis, the detailed mechanism of the
      electron transfer process and crucial molecules that control this reaction have
      only recently come into focus. The reactive behavior of the Ag NMs is of great
      significance for understanding their overall behavior and toxicity. Additionally,
      only limited knowledge is available about their kinetics. All reactions involve
      chemical bond formation, electron transfer, or electrostatic interactions. An
      overview is presented of the biosynthesis of Ag NMs based on molecular supports
      including a nitrate reductase/NADH oxidase-involved electron transfer reaction
      and their mechanisms in Ag+ reduction: quinol-mediated mechanism and superoxide
      dependent mechanism, and molecular supports in plant extracts, is presented. The
      environmental reaction kinetics and mechanisms of the interactions of Ag NMs with
      substances are introduced based on the formation and classification of chemical
      bonds. The particle-particle reaction kinetics of Ag NMs in the environment are
      discussed to directly explain their stability and aggregation behavior. The
      toxicity of Ag NMs is also presented. In addition, future prospects are
      summarized. This review is the first to provide an insight into the mediating
      molecules and chemical bonds involved in the biosynthesis, kinetics, and
      mechanisms of action of Ag NMs.

PMID- 30189551
TI  - The effects of emerging environmental contaminants on Stenotrophomonas
      maltophilia isolated from drinking water in planktonic and sessile states.
AB  - Concerns on the presence of emerging contaminants (ECs) in water sources have
      increased in recent years. The lack of efficient technologies to remove ECs from
      residual waters contributes for their appearance in drinking water distribution
      systems (DWDS). Therefore, sessile microorganisms on DWDS pipes are continuously
      exposed to trace concentrations of ECs. However, no data exists on the role of
      ECs on the resident microbiota. The present work aims to understand the effects
      of prolonged exposure of a bacterial strain of Stenotrophomonas maltophilia,
      isolated from a DWDS, in both planktonic and biofilm states, to trace
      concentrations of selected ECs (antipyrine-ANTP; diclofenac sodium salt-DCF;
      ibuprofen-IBP; galaxolide-GAL; tonalide-TON; carbamazepine-CBZ; clofibric acid
      CA; tylosin-TY) on its tolerance to sodium hypochlorite (NaOCl) and resistance to
      antibiotics. Pre-established S. maltophilia biofilms were exposed to ECs for 26
      d. Subsequently, the planktonic behaviour of the biofilm cells grown in the
      presence of ECS was characterized in terms of susceptibility to NaOCl and to
      selected antibiotics (levofloxacin and trimethoprim-sulfamethoxazole). Moreover,
      S.maltophilia was tested on its biofilm productivity in the presence of ECs
      (alone and mixed). These biofilms were challenged by NaOCl in order to assess the
      role of ECs on biofilm susceptibility. The results did not evidence remarkable
      effects of ECs on planktonic S. maltophilia susceptibility to NaOCl and
      antibiotics. However, S. maltophilia biofilm production and susceptibility to
      NaOCl was affected from ECs pre-exposure, particularly by the combination of
      different ECs (CA + CBZ, CA + IBP, CA + CBZ + IBP). S. maltophilia biofilms
      became more resistant to removal by NaOCl when developed in the presence of
      mixtures of CA + CBZ and CA + CBZ + IBP. Also, biofilm production was
      significantly affected. CA was present in all the combinations that altered
      biofilm behaviour. The overall results propose that exposure to ECs for 26 days
      had not a huge impact on S. maltophilia planktonic antimicrobial susceptibility.
      Nevertheless, the prolonged exposure to some ECs altered biofilm production and
      tolerance to NaOCl, with a potential practical outcome of hindering DWDS
      disinfection. The simultaneous presence of different ECs in the environment may
      amplify biofilm resilience.

PMID- 30189552
TI  - Effects of snow depth manipulation on the releases of carbon, nitrogen and
      phosphorus from the foliar litter of two temperate tree species.
AB  - The effect of snow depth on litter decomposition in cold regions has attracted
      substantial attention, but the importance of snow depth to the releases of carbon
      (C), nitrogen (N), and phosphorus (P) and the underlying mechanisms remain
      unclear. The releases of C, N, and P from the foliar litter of Pinus koraiensis
      and Quercus mongolica in response to snow depth changes were examined for 12
      months in a temperate forest of Northeast China via a snow depth manipulation
      experiment that included snow-addition (SA), snow-removal (SR), and control (CK)
      treatments. We found that the SA treatment promoted the releases of C, N, and P
      from the foliar litter during the snow-covered season but slowed these processes
      during the following snow-free season; however, the SR treatment produced the
      opposite results. Compared with the CK treatment, the SA treatment increased the
      annual releases of C, N, and P by 2.52%, 0.50%, and 4.68%, respectively, whereas
      the SR treatment decreased the corresponding values. The elemental release during
      the snow-covered season was associated with the freeze-thaw cycle (FTC) and
      microbial biomass, whereas that during the snow-free season was mainly controlled
      by the temperature of the litter layer. Our findings indicated that the snow
      depth promoted the releases of C, N and P from the foliar litter of the two tree
      species, especially during the snow-covered season. These results deepen the
      understanding of the biogeochemical cycling in cold regions under global climate
      change scenarios.

PMID- 30189553
TI  - Role of surfactant headgroups on the toxicity of SLEnS-LAS mixed micelles: A case
      study using microtox test.
AB  - Mixtures containing ether sulfate based surfactants (SLEnS) and linear
      alkylbenzene sulfonic acid (LAS) are relatively common in personal care and
      household products. When in mixture, they form mixed micelles, which act as
      reservoirs for the cleaning process. The increase of ethylene oxide (EO) units in
      the head of SLEnS lowers the critical micelle concentration, meaning that less
      quantity of each surfactant is needed to form the micelles. Within an eco
      friendly perspective this is advantageous since less chemicals are expected to be
      released into the environment. But, this advantage will only be effective if
      variations with the higher number of EO units exhibit a lower toxicity as well.
      Despite its wide use in commercial products, the ecotoxicity of these micelles
      and the influence of the EO units on their toxicity still did not receive the
      necessary attention. In this context, the present study aimed at assessing the
      influence of the number of ethylene oxide (EO) units in the head groups of SLEnS
      on the toxicity of the SLEnS-LAS mixed micelles to the bacterium Vibrio fischeri
      (Microtox(r) assay, here used as a fast and preliminary ecotoxicological
      indicator). The SLEnS variants with fewer EO units showed higher toxicity
      relatively to those with more EO units - EC50 range (0-50 EO units): 0.56-8.59 mg
      L-1, thus they can be suggested as environmentally safer variants to be used in
      personal care and household products. Provided the consistency of Microtox(r)
      results as obtained here, this quick and cost-effective procedure can be an
      important tool towards the development of eco-friendlier surfactant-based
      formulations.

PMID- 30189554
TI  - Contribution of deltaic wetland food sources to coastal macrobenthic consumers
      (Po River Delta, north Adriatic Sea).
AB  - Estuaries are known to export huge quantities of terrigenous/riverine organic
      matter and nutrients to coastal areas, subsidizing food sources to their
      communities; however, this process is seldom investigated in complex multichannel
      delta-prodelta systems. Stable isotope analysis was used to investigate the
      contribution of organic sources originated from the Po River Delta, one of the
      widest deltaic wetlands in the northern Mediterranean Sea, to the diet of the
      nearby coastal macrobenthic consumers, and their influence on invertebrates'
      trophic structure and biomass. Following intense river flood events, macrofauna
      samples were collected in the prodelta area at increasing distance from the main
      river distributary mouth. Potential primary resources were collected within the
      delta and the prodelta areas. A terrestrial signal in the primary consumers' diet
      was evident as a shift in their delta13C, being this more 13C depleted near the
      main river distributary. The Bayesian mixing models indicated an important
      contribution of deltaic sources, in particular C4-grass detritus (25-57%), to
      primary consumers' diet, confirming a strong energetic link between delta and
      prodelta areas. Overall, most of the consumers' biomass were concentrated at
      sites close to the main distributary mouth, mainly as suspension and surface
      deposit feeders. A simplification of the macrobenthic community structure,
      accompanied by narrower transfer pathways was also evident at sites more distant
      from the main river distributary, in relation to changes in the quality of
      resources. Our data, although limited to winter season, suggest that during
      periods of low in situ productivity but high river flow energy, invertebrates are
      able to efficiently exploit terrigenous food sources, restraining the detrimental
      effect of increased turbidity and sedimentation. We conclude that
      riparian/wetland vegetation associated with river deltas can provide important
      food sources to marine primary consumers. These results furthermore highlight the
      need for integrated management and protection strategies of connected land-sea
      ecosystems.

PMID- 30189555
TI  - Micro food web networks on suspended sediment.
AB  - The genesis of suspended aggregates in aquatic ecosystems is not only a result of
      hydrodynamic mineral interactions but also a complex microbial food web network.
      A microbiological-physical model (BFLOC2) is introduced here to predict aggregate
      geometry and settling velocity under simultaneous effects of hydrodynamic and
      biological processes. While minerals can contribute to aggregate dynamics through
      collision, aggregation, and breakup, living microorganisms can colonize and
      establish food web interactions that involve growth and grazing, and modify the
      aggregate structure. The BFLOC2 model describes the aggregate dynamics resulting
      from interactions between minerals and three types of microorganisms, namely
      bacteria, flagellates, and ciliates. BFLOC2 was first calibrated against the size
      and capacity (fractal) dimension of aggregates formed in a pure mineral system at
      different mineral concentrations and fluid shear rates, and then against the
      abundance of aggregate-attached cells in a pure microbial environment. BFLOC2
      model and calibrated parameters were then tested against biomineral aggregate
      size, capacity dimension, and biomass fraction formed in biomineral flocculation
      experiments at four nutrient concentrations. Modelling of biomineral aggregate
      dynamics over a wide range of environmental conditions showed that maximum
      aggregate size, biomass fraction, and settling velocity could occur at different
      optimal environmental conditions. Unlike mineral aggregates, which have maximum
      size when shear rate tends to zero, a relative maximum size of biomineral
      aggregates can be reached at intermediate shear rates as a result of
      microbiological processes. The settling velocity was ultimately controlled by
      aggregate size, capacity dimension, and biomass fraction. Microorganism dynamics
      including cell motility and food web network interactions significantly
      controlled aggregate-attached cell abundance and aggregate dynamics.

PMID- 30189556
TI  - Polarized but illusory beliefs about tap and bottled water: A product- and
      consumer-oriented survey and blind tasting experiment.
AB  - BACKGROUND: Despite the rigorous control of tap water quality, substantial price
      differences, and environmental concerns, bottled water consumption has increased
      in recent decades. To facilitate healthy and sustainable consumer choices, a
      deeper understanding of this "water consumption paradox" is needed. Therefore,
      the aim of the two present studies was to examine health-related beliefs and risk
      perceptions and their accuracy by implementing a combined product- and consumer
      oriented approach. METHODS: An online survey (N = 578) and a blind taste test (N
      = 99) assessed perceptions and behaviors for tap and bottled water within
      primarily tap and bottled water consumers in a fully crossed design. The combined
      product- and consumer-oriented approach yielded significant consumer * product
      interaction effects. RESULTS: The two consumer groups showed "polarized" ratings
      regarding perceived quality/hygiene, health risks and taste for bottled and tap
      water, indicating that the two consumer groups substantially diverged in their
      beliefs. However, in the blind taste test, neither consumer group was able to
      distinguish tap from bottled water samples (consumer perspective). Moreover, tap
      or bottled water samples did not systemically vary in their ascribed health-risk
      or taste characteristics (product perspective). CONCLUSIONS: Although the two
      consumer groups differ greatly in their beliefs, the perceived health risk and
      taste differences seem to reflect illusionary beliefs rather than actual
      experiences or product characteristics. Public health campaigns should address
      these illusions to promote healthy and sustainable consumer choices.

PMID- 30189557
TI  - Greenhouse gas emissions and water footprints of typical dietary patterns in
      India.
AB  - Agriculture is a major contributor to India's environmental footprint,
      particularly through greenhouse gas (GHG) emissions from livestock and fresh
      water used for irrigation. These impacts are likely to increase in future as
      agriculture attempts to keep pace with India's growing population and changing
      dietary preferences. Within India there is considerable dietary variation, and
      this study therefore aimed to quantify the GHG emissions and water usage
      associated with distinct dietary patterns. Five distinct diets were identified
      from the Indian Migration Study - a large adult population sample in India -
      using finite mixture modelling. These were defined as: Rice & low diversity, Rice
      & fruit, Wheat & pulses, Wheat, rice & oils, Rice & meat. The GHG emissions of
      each dietary pattern were quantified based on a Life Cycle Assessment (LCA)
      approach, and water use was quantified using Water Footprint (WF) data. Mixed
      effects regression models quantified differences in the environmental impacts of
      the dietary patterns. There was substantial variability between diets: the rice
      based patterns had higher associated GHG emissions and green WFs, but the wheat
      based patterns had higher blue WFs. Regression modelling showed that the Rice &
      meat pattern had the highest environmental impacts overall, with 0.77 (95% CI
      0.64-0.89) kg CO2e/capita/day (31%) higher emissions, 536 (95% CI 449-623)
      L/capita/day (24%) higher green WF and 109 (95% CI 85.9-133) L/capita/day (19%)
      higher blue WF than the reference Rice & low diversity pattern. Diets in India
      are likely to become more diverse with rising incomes, moving away from patterns
      such as the Rice & low diversity diet. Patterns such as the Rice & meat diet may
      become more common, and the environmental consequences of such changes could be
      substantial given the size of India's population. As global environmental stress
      increases, agricultural and nutrition policies must recognise the environmental
      impacts of potential future dietary changes.

PMID- 30189558
TI  - Toxic effects of copper sulfate on diploid and triploid fin cell lines in
      Misgurnus anguillicaudatus.
AB  - The effects of different concentrations of copper sulfate on diploid and triploid
      fin cell lines (named DIMF and TRMF, respectively) in Misgurnus anguillicaudatus
      were studied. The LC50 of copper sulfate estimated by an MTT assay was 268.39 in
      DIMF cells, and 311.54 MUmol/L in TRMF cells, respectively. Activity of
      superoxide dismutase (SOD) in DIMF cells gradually increased as the concentration
      of copper sulfate increased (up to 200 MUmol/L), and then gradually decreased.
      SOD activity in triploid loach fin cells, as well as glutathione peroxidase (GSH
      Px) and glutathione-S-transferase (GST) activity in both diploid and triploid
      cells, decreased as the concentration of copper sulfate increased, which
      suggested that excessive copper exposure at the concentrations tested in this
      study was detrimental to anti-oxidative capability. In general, SOD, GST and GSH
      Px activity was higher in triploid fin cells than in diploid cells. DNA breaks
      were observed by comet assays after 24 h exposure to 400 and 800 MUM copper; DNA
      percent in the comet's tail was lower in TRMF than in DIMF. Ultrastructurally,
      there were no significant differences in the organelles of both cells, although a
      higher number of vesicles were observed in TRMF cells after copper exposure.
      Pathological changes induced by copper sulfate were similar in DIMF and TRMF
      cells, and were indicative of cell necrosis. Results above suggested that
      excessive copper sulfate exposure would lead to antioxidant enzymes activity
      reduction, along with antioxidant defenses disruption and superoxide radicals
      increasing, and then to DNA damage, ultrastructural changes and necrosis features
      in DIMF and TRMF M. anguillicaudatus fin cells. Triploid cell lines had higher
      resistance to copper than their diploid counterparts especially at higher
      concentrations of copper due to larger cells and higher intracellular content of
      detoxification enzymes to resist the toxicity of heavy metals.

PMID- 30189559
TI  - Responses of soil respiration and its components to experimental warming in an
      alpine scrub ecosystem on the eastern Qinghai-Tibet Plateau.
AB  - The responses of soil respiration (Rs) to warming are driven by its components,
      that is, heterotrophic respiration (Rh) and rhizosphere respiration (Rr,
      including fine root respiration [Rfr] and rhizomicrobial respiration [Rz]).
      However, the effects of warming on Rs and its components are rarely studied in
      alpine scrub ecosystems on the Qinghai-Tibet Plateau. Here, we conducted a
      warming experiment to examine how Rs and its components respond to experimental
      warming. We found that one-year experimental warming (increased by 1.3  degrees
      C) significantly stimulated the rates of Rs, Rh and Rr by 21.6, 23.8, and 21.1%,
      respectively. The annual cumulative C effluxes of Rs increased by 87.87 g m-2
      with nearly equal contributions from Rh (46.84 g m-2) and Rr (41.03 g m-2) under
      warming. Moreover, warming-induced increase in Rr mainly resulted from increased
      Rfr rather than Rz due to the significant increase in fine root biomass and Rfr
      rate. In addition, the Q10 values for Rs, Rh and Rr were also increased by
      experimental warming, while the contribution of Rh to Rs was not altered by
      experimental warming. Collectively, our results suggest that future climatic
      warming will stimulate more C releases from soil to the atmosphere through an
      enhancement of both Rh and Rr in these alpine scrub ecosystems on the Qinghai
      Tibet Plateau.

PMID- 30189560
TI  - Adsorption and desorption of nitrous oxide by raw and thermally air-oxidized
      chars.
AB  - Addition of biomass chars (biochar) to soil reportedly suppresses emissions of
      nitrous oxide (N2O), a potent greenhouse and ozone-depleting gas, but the causes
      and endurance of the effect are unclear. To determine whether adsorption may play
      a role, adsorption isotherms of N2O were constructed at 273 K on outgassed
      samples of anoxically-prepared wood-derived chars (300-700  degrees C) and on a
      subset briefly reheated in air at 400  degrees C. Sorption by the chars was
      greater and more reversible than sorption by soils or soil mineral phases.
      Adsorption by chars increased with pyrolysis temperature and upon post-pyrolysis
      air oxidation. The Langmuir maximum capacity correlates well with the CO2
      determined (but not N2-B.E.T.-determined) surface area. At environmentally
      realistic partial pressures in soil, N2O adsorption correlates with CO2
      adsorption, and is found to predominate in the micropores (<1.5 nm), especially
      ultramicropores (<0.7 nm). Neither adsorption nor adsorption reversibility was
      affected by coating the char with soil organic matter extract. It is concluded
      that char added at levels above 1% in soil would act as a strong and reversible
      sink for N2O, and could be responsible for the temporary nature of N2O emission
      suppression observed in some cases.

PMID- 30189561
TI  - Anaerobic degradation of sulfamethoxazole in mangrove sediments.
AB  - The effects of sucrose and electron acceptors on the anaerobic degradation of
      sulfamethoxazole (SMX) in mangrove sediments were investigated in this study.
      Among three sulfonamides, sulfamethoxazole, sulfadimethoxine and sulfamethazine,
      only SMX could be completely degraded in mangrove sediments. Degradation of SMX
      was enhanced by the addition of sucrose to the sediments. The degradation rates
      of SMX were increased in bioreactor experiments with sucrose. The addition of
      electron acceptors (sodium hydrogen carbonate, sodium sulfate, and sodium
      nitrate) could further enhance SMX degradation. The order of anaerobic SMX
      degradation rates under three different conditions was as follows: sulfate
      reducing conditions > methanogenic conditions > nitrate-reducing conditions.
      Methanolobus, Desulfuromonas, and Thauera were found in the highest proportions
      among methanogens, sulfate-reducing bacteria and denitrifying bacteria,
      respectively. Achromobacter, Brevundimonas, Delftia, Idiomarina, Pseudomonas, and
      Rhodopirellula were the major bacterial communities responsible for SMX
      degradation in the sediment. Overall, 16 bacterial and archaeal genera were
      identified as the core microbial community facilitating anaerobic SMX degradation
      for all methanogenic, sulfate-reducing and nitrate-reducing conditions. The
      results of this study provide feasible methods for the removal of SMX from
      mangrove sediments.

PMID- 30189562
TI  - Chronic toxicity of metolachlor OA on growth, ontogenetic development,
      antioxidant biomarkers and histopathology of early life stages of marbled
      crayfish.
AB  - The metolachlor OA is a metabolite of herbicide metolachlor and s-metolachlor.
      The objective of the present study was to assess the effect metolachlor OA on
      early life stages of marbled crayfish (Procambarus virginalis). The early life
      stages of marbled crayfish were exposed for 45 days to three concentrations of
      metolachlor OA: 4.2 MUg/L (environmentally relevant concentration, E1), 42 MUg/L
      (E2) and 420 MUg/L (E3) under laboratory conditions. The effects were assessed on
      the basis of mortality, growth, ontogenetic development, behaviour, oxidative
      stress, antioxidant biomarkers and histopathology. Metolachlor OA caused
      significantly lower growth, superoxide dismutase, catalase and glutathione s
      transferase activity in all tested concentrations. Metolachlor OA in higher
      concentrations (42 and 420 MUg/L) resulted in significantly delayed ontogenetic
      development, lower reduced glutathione level and lipid peroxidation. Metolachlor
      OA has not significant effect on behaviour (activity, total distance moved and
      walking speed). Histological examination revealed alteration of hepatopancreas
      and gills in crayfish exposed to two higher tested concentrations. Hepatopancreas
      reflected histomorphological structural changes of individual cell types. Changes
      of gills included focal hemocytic infiltration together with enlargement of
      intralamellar space packed with granular substance. In conclusion, chronic
      metolachlor OA exposure affected growth, ontogenetic development, and the
      antioxidant system and caused pathological changes in hepatopancreas and gills of
      early life stages of marbled crayfish.

PMID- 30189563
TI  - Micropollutants removal in tertiary moving bed biofilm reactors (MBBRs):
      Contribution of the biofilm and suspended biomass.
AB  - The performance of tertiary moving bed biofilm reactors (MBBRs) was evaluated in
      terms of micropollutants (MPs) removal from secondary-treated municipal
      wastewater. After stepwise establishment of a mature biofilm, monitored by
      scanning electron and confocal microscopies, abiotic and biotic removals of MPs
      were deeply studied. Since no MPs reduction was observed by the both
      photodegradation and volatilization, abiotic removal of MPs was ascribed to the
      sorption onto the biomass. Target MPs i.e. Naproxen, Diclofenac, 17beta-Estradiol
      and 4n-Nonylphenol, arranged in the ascending order of hydrophobicity,
      abiotically declined up to 2.8%, 4%, 9.5% and 15%, respectively. MPs sorption
      onto the suspended biomass was found around two times more than the biofilm, in
      line with MPs' higher sorption kinetic constants (ksor) found for the suspended
      biomass. When comparing abiotic and biotic aspects, we found that biotic removal
      outperformed its counterpart for all compounds as Diclofenac, Naproxen, 17beta
      Estradiol and 4n-Nonylphenol were biodegraded by 72.8, 80.6, 84.7 and 84.4%,
      respectively. The effect of the changes in organic loading rates (OLRs) was
      investigated on the pseudo-first order degradation constants (kbiol), revealing
      the dominant biodegradation mechanism of co-metabolism for the removal of
      Diclofenac, Naproxen, and 4n-Nonylphenol, while 17beta-Estradiol obeyed the
      biodegradation mechanism of competitive inhibition. Biotic removals and kbiol
      values of all MPs were also seen higher in the biofilm as compared to the
      suspended biomass. To draw a conclusion, a quite high removal of recalcitrant MPs
      is achievable in tertiary MBBRs, making them a promising technology that supports
      both pathways of co-metabolism and competitive inhibition, next to the abiotic
      attenuation of MPs.

PMID- 30189564
TI  - Removal of anti-inflammatory/analgesic pharmaceuticals from urban wastewater in a
      pilot-scale A2O system: Linking performance and microbial population dynamics to
      operating variables.
AB  - In this study, the removal rates of eight anti-inflammatory and/or analgesic
      pharmaceuticals, AIAPs (acetaminophen, ibuprofen, naproxen, ketoprofen,
      diclofenac, codeine, indomethacin and propyphenazone) were assessed in a pilot
      scale A2O system (including anaerobic/anoxic/aerobic zones), long term operated
      during two experimental phases using different sets of environmental conditions
      and operating parameters. qPCR was used to quantify the absolute abundances of
      total Bacteria, total Archaea, mycolic-acid containing filamentous Actinobacteria
      (Mycolata) and Fungi within the activated sludge microbial community developed in
      the system. Multivariate analyses and Spearman correlation coefficients were used
      in search of significant links among the removal rates of the AIAPs, the
      abundances of the targeted microbial groups in the activated sludge, and the
      changes of environmental/operating variables in the A2O system. Improved removal
      efficiencies of several of the AIAPs analyzed (acetaminophen, ibuprofen,
      naproxen, ketoprofen) were correlated to higher organic load in the influent
      water, higher concentration of mixed liquor suspended solids (MLSS), lower
      temperature and lower food-to-microorganisms ratio (F/M). Removal efficiencies of
      several pharmaceuticals correlated with increased abundances of Mycolata in the
      A2O system, pointing at this group of bacteria as candidate key players for AIAPs
      removal in activated sludge.

PMID- 30189565
TI  - Ten years of application of sewage sludge on tropical soil. A balance sheet on
      agricultural crops and environmental quality.
AB  - Sewage sludge (SS) has been used in agriculture on a large scale in Europe. In
      tropical climate conditions, due to rapid organic matter degradation, SS can
      provide toxic elements that can cause damage to the environment. We evaluated an
      area that received doses of SS for 10 years compared to mineral fertilization.
      The biogeochemical parameters (amylase, cellulase, invertase and dehydrogenase
      activity, carbon microbial biomass, basal respiration, metabolic quotient,
      soluble carbohydrates, total carbohydrates and glucose) and maize agronomic
      performance were evaluated. There was no increase of organic matter in the area
      due to the SS application. However, the application of SS for 10 consecutive
      years influenced the biogeochemical parameters evaluated in a similar way to the
      area that received mineral fertilizer. The SS proved efficient in completely
      replacing P fertilization and micronutrients. SS can also partially replace N
      fertilization without reducing maize productivity.

PMID- 30189566
TI  - Spatial distribution of metal pollution of soils of Chinese provincial capital
      cities.
AB  - This work describes the spatial distribution of metal concentrations, resulting
      environmental quality, and potential ecological risks using ArcGIS. The data were
      based on collecting the soil background and baseline values of eight metal
      elements (As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn) in 31 Chinese provincial capital
      cities (PCCs) from published literatures 2005-2017. The following results were
      obtained in accordance with the integrated pollution index and the total
      potential ecological risk index: (1) The average concentrations of metals varied
      in relatively low degree in Chinese PCCs, while 10 and six PCCs were classified
      as having "severe" contamination and "moderate" risk, respectively. (2) Cd, Hg,
      Cu, Pb, and Zn were chosen as priority control metals; Beijing, Chengdu, Tianjin,
      Changsha, Shijiazhuang, Shenyang, Ji'nan, Changchun, and Xi'an were chosen as
      priority control PCCs, due to their higher pollution level and ecological risk of
      soils in comparison to other metals or PCCs. (3) A clear southeast/northwest
      boundary marked the urban soil metal pattern, which was aligned with the famous
      demographic, geological, and economic boundary known as the "Hu-line." This
      finding suggests that metal contamination in urban soil was caused by both
      geochemical background and human activities. These results provide basic
      information that can assist to avoid further degradation of soil by preventing
      and monitoring metal contamination in China's PCCs. The study suggests that more
      attention should be focused on developing cities in western China and "The Belt
      and Road" when pursuing economic development.

PMID- 30189567
TI  - Effects of salinity and transparent exopolymer particles on formation of aquatic
      aggregates and their association with norovirus.
AB  - Human noroviruses (NoVs) are responsible for 50% of food-related disease
      outbreaks and are notably associated with shellfish consumption. Despite the
      detrimental health impacts of human NoV-contaminated seafood to public health,
      there is a lack of knowledge on the physicochemical conditions that govern NoV
      transmission in aquatic ecosystems. In the present study, we investigated the
      propensity for NoVs to associate with aquatic aggregates, which have been shown
      to efficiently deliver nano-sized particles to shellfish. Specific
      physicochemical conditions characteristic of shellfish cultivation waters,
      specifically salinity and transparent exopolymer particles (TEP), were targeted
      in this study for investigating aggregate formation and NoV association dynamics.
      Murine norovirus (MNV) was used in aggregation experiments as a model surrogate
      for NoVs. Results demonstrate increased aggregate formation as a function of
      increasing salinity and TEP concentrations, as well as greater numbers of MNV
      genomes incorporated into aggregates under conditions that favor aggregation. As
      aggregate formation was enhanced in waters representing optimal conditions for
      shellfish production, specifically saline and high TEP waters, the implications
      to virus transport and shellfish food safety are profound: more aggregates
      implies increased scavenging of virus particles from surrounding waters and
      therefor greater risk for bivalve contamination with nano-sized pathogens. These
      novel data provide insight into where and when NoVs are most likely to be
      ingested by shellfish via contaminated aggregates, thereby informing best
      management and water quality monitoring practices aimed at providing safe seafood
      to consumers.

PMID- 30189568
TI  - Multidimensional relationships of herbicides with insect-crop food webs.
AB  - Controlling weeds is critical for improving the yield and quality of crops.
      Herbicides are the most commonly applied pesticides in agro-ecosystems.
      Herbicides affect insects directly as contact damage and indirectly by
      influencing food supplies. The innate susceptibility, life stages, and mode of
      feeding of insects can affect the herbicide-insect interaction. Interaction of
      herbicides with insect pest and beneficial insects is mainly indirect and absence
      of weeds either can reduce the insect population or causes switching of host
      plant and hence can also increase the population. The direct effect of herbicides
      depends on carrier or surfactant used. Presence of herbicides also provides
      surfactant to insecticides and increases impact of insecticides. At present, most
      reports on impact of herbicides indicate alterations in insect survival or egg
      production due to increase or decrease in host plant population as an indirect
      affect, only a handful studies reported a direct topical effect of these
      herbicides on egg, larvae/nymphs and adults of various insects. Further
      exploration of this interaction seems intriguing. Use of bio-herbicides, cultural
      control methods, and judicious use of herbicides could offer ecologically
      sustainable approaches to reduce impact of herbicides on insects.

PMID- 30189569
TI  - Identification of pesticide exposure-induced metabolic changes in mosquito
      larvae.
AB  - The European regulatory framework for pesticides generally applies an assessment
      factor of up to 100 below the acute median lethal concentration (LC50) in
      laboratory tests to predict the regulatory acceptable concentrations (RACs).
      However, long-term detrimental effects of pesticides in the environment occur far
      below the RACs. Here, we explored the metabolic changes induced by exposure to
      the neonicotinoid insecticide clothianidin in larvae of the mosquito Culex
      pipiens. We exposed the test organisms to the insecticide for 24 h and then
      measured the levels of 184 metabolites immediately and 48 h after the pulse
      contamination. We established a link between the exposure to clothianidin and
      changes in the level of three specific classes of metabolites involved in energy
      metabolism, namely, glycerophospholipids, acylcarnitines and biogenic amines.
      Remarkably, exposure to concentrations considered to be safe according to the
      regulatory framework (2-4 orders of magnitude lower than the acute LC50), induced
      longer-term effects than exposure to the highest concentration. These results
      suggest that a specific detoxification mechanism was only triggered by the
      highest concentration. We conclude that even very low insecticide concentrations
      increase the energy demands of exposed organisms, which potentially translates
      into a decline in sensitive species in the field.

PMID- 30189570
TI  - Social impacts of occupational heat stress and adaptation strategies of workers:
      A narrative synthesis of the literature.
AB  - Dimensions of risks and impacts of occupational heat stress due to climate change
      on workers' health and safety, productivity, and social well-being are
      significantly deleterious. Aside from empirical evidence, no systematic review
      exists for policy development and decision making in managing occupation heat
      stress impacts and adaptation strategies of workers. This study sought to
      synthesise evidence on the social impacts of occupational heat stress and
      adaptation strategies of workers. From a review of existing literature, eight
      categories were obtained from 25 studies and grouped into three syntheses: (1)
      awareness of occupational heat stress, (2) social impacts of occupational heat
      stress and (3) workers' adaptation to occupational heat stress due to changing
      climate. Awareness of occupational heat stress among workers varied and their
      social impacts were related to workers' health and safety, productivity and
      social well-being. Sustainable adaptation to occupation heat stress due to
      climate change hinges on financial resource availability. Adequate investment and
      research are required to develop and implement policies to combat the threat of
      rising temperature and climate change to enhance workers' adaptive capacity,
      boost resilience and foster sustainable development.

PMID- 30189571
TI  - Simulating urban expansion and its impact on functional connectivity in the Three
      Gorges Reservoir Area.
AB  - Understanding the impact of urban expansion on functional connectivity is
      significant to biodiversity conservation. Particularly, in the Three Gorges
      Reservoir Area (TGRA, Southwest China), the urban land has rapidly expanded to
      provide settlements for an enormous population of TGRA migrants. However, the
      consequence of future land-use changes to the functional connectivity of the
      local habitat network has rarely been studied. To extend this knowledge, this
      paper proposes a framework that integrates a novel cellular automata (CA)
      simulation model and ecological network analysis, taking the TGRA as the study
      area, to predict how different urban expansion scenarios might affect functional
      connectivity for a nationally protected species, the leopard. The least-cost path
      modeling is used, and a set of connectivity indicators are adopted to evaluate
      functional connectivity. The results show that, the population-growth-based urban
      expansion maintains a higher connectivity than the business-as-usual and fast
      urban-growth scenarios. In addition, the connectivity loss due to urban expansion
      can be offset by the reforestation efforts of the Green-for-Grain Project.
      Finally, we identify habitat patches that act as key connectivity providers, and
      suggest that those patches be prioritized for protection to avoid significant
      connectivity loss.

PMID- 30189572
TI  - Persistence and availability of veterinary antibiotics in soil and soil-manure
      systems.
AB  - The availability and persistence of various antibiotics in soil and soil amended
      with composted poultry manure were investigated through laboratory incubation
      assays. Six veterinary antibiotics (one fluoroquinolone, two tetracyclines, two
      sulfonamides and one lincosamide) and one active metabolite (ciprofloxacin) were
      studied. The incubation assays were conducted at a controlled temperature of 25 
      degrees C with different water regimes, such as constant moisture content (80% of
      water holding capacity) and drying-rewetting cycles. The studied antibiotics were
      determined in soil and soil aqueous phase samples by LC-MS/MS using internal
      standards. The results indicated that the highest levels found in the soil
      aqueous phase were for sulfamethoxazole, followed by sulfamethazine and
      lincomycin, being very low the levels of chlortetracycline, doxycycline,
      ciprofloxacin and enrofloxacin (<=1.8%). A positive correlation was observed
      between the antibiotic concentrations and the content of the dissolved organic
      carbon in soil aqueous phase with the incubation time. An increase in the
      apparent sorption coefficients of these antibiotics, except chlortetracycline and
      lincomycin, was observed when the soil was amended with composted manure. Except
      for fluoroquinolones, with remaining residues around 70% after 90 days of
      incubation, a fast dissipation of antibiotics was observed during the assay, with
      half-lives ranging from 8 to 27 days. These values increased between 6% and 53%
      in manure amended soil; nevertheless, half-lives remained short (9 days and 27
      days for lincomycin and sulfamethazine, respectively). Similar results were
      obtained with soil under drying-rewetting cycles showing somewhat lower values in
      soil aqueous phase and slightly shorter half-lives in some cases. The results
      obtained pointed out that the route of entry of antibiotics into the soil,
      through recycled water or manure, may have an important effect on their behavior,
      particularly regarding their availability in soil.

PMID- 30189573
TI  - Assessing long-term stability of cadmium and lead in a soil washing residue
      amended with MgO-based binders using quantitative accelerated ageing.
AB  - A soil washing residue (SWR) (containing 90% clay, cadmium (Cd2+) of 132 mg/kg,
      lead (Pb2+) of 3410 mg/kg) was stabilized with MgO (M) and MgO + bioapatite (MB)
      respectively at a dosage of 5% in w/w. The stability of the metals in original
      and amended SWRs was assessed after immediate treatment and using a laboratory
      accelerated ageing method simulating 26, 52, 78 and 104 years in field
      conditions. The dissolved Cd2+ and Pb2+ from the SWR in Toxicity Characteristic
      Leaching Procedure (TCLP) leachates significantly reduced (by 96.84-99.06%) by
      both amendments after immediate treatment. The stabilization remained effective
      within simulated 26 years as the TCLP leached Cd2+ and Pb2+ kept below regulatory
      levels. This immobilization was mainly due to the increased non-bioavailable Cd2+
      and Pb2+ from sequential extraction tests in SWR by the amendments. At simulated
      52 years, the TCLP leached Cd2+ from M and MB exceeded regulatory level by 106%
      and 1% respectively. Large amounts of Cd2+ and Pb2+ were leached out by 36.74
      48.18% regardless of the treatments at simulated 104 years. Although bioapatite
      can significantly aid the stabilization of metals by MgO, the stabilization
      effectiveness for both treatments diminished at simulated 52 years and from 52 to
      104 years.

PMID- 30189575
TI  - Renewable energy, nuclear energy, and environmental pollution: Accounting for
      political institutional quality in South Africa.
AB  - This study examined the impact of disaggregate and aggregate energy, economic
      development, urbanization and political institutional quality on environmental
      pollution using a time series data spanning from 1971 to 2017. The study employed
      response surface regressions, structural break cumulative sum (CUSUM) test based
      on recursive residuals and ordinary least squares (OLS) residuals for parameter
      stability en route to estimating the autoregressive distributed lag (ARDL)
      regression. The environmental Kuznets curve (EKC) hypothesis is valid in South
      Africa with an extreme point of ZAR 56,114 which occurred in 2011. Evidence from
      the study reveals that political institutional quality plays a huge role in the
      social, governance and economic readiness to mitigate climate change and its
      impact. Structural adjustment in disaggregate and aggregate energy consumption,
      economic growth, and political institutional quality play a critical role in
      environmental quality. Fossil-fuel rich countries require diversification of the
      energy portfolio by incorporating renewable energy sources which will promote
      environmental sustainability and improve air quality while reducing their
      economy's vulnerability to price volatility. A paradigm shift from energy and
      carbon-intensive industries to a service-oriented economy will cause a structural
      economic change thus, aiding in the mitigation of climate change and its impacts.

PMID- 30189574
TI  - Environmental impacts of small-scale hybrid energy systems: Coupling solar
      photovoltaics and lithium-ion batteries.
AB  - One of the benefits of hybrid solar PV-battery systems is that they can reduce
      grid dependency and help balance electricity supply and demand. However, their
      environmental impacts and benefits remain underexplored. This study considers for
      the first time life cycle environmental impacts of domestic-scale PV-battery
      systems in Turkey, integrating multi-crystalline PV and lithium-ion battery. The
      impacts were estimated for both individual installations and at the national
      level, considering different regions across the country and taking into account
      their insolation and other climatic differences. Electricity generation and
      storage were modelled on an hourly basis taking into account consumer behaviour.
      The results show that the system can meet between 12.5% and 18.4% of the
      household's annual electricity needs. On a life cycle basis, it generates 4.7-8
      times more energy than it consumes. Solar PV is the major contributor to most
      impacts (75%-81%). An exception is human toxicity which is mainly due to the
      battery (66%). The hybrid system has 1.6-82.6 times lower impacts than grid
      electricity. Assuming a very modest uptake at the national level (2%-8%), the use
      of hybrid systems would save 558,000 t CO2-eq./yr compared to grid electricity.
      Thus, these results demonstrate clearly the environmental benefits of these
      hybrid systems. Together with the financial and energy security benefits for both
      the country and the consumer, this provides a strong impetus for their wider
      deployment. However, this will be difficult to achieve, as there are no
      incentives for battery storage. Therefore, it is recommended that relevant
      legislation be introduced to stimulate future uptake of hybrid PV-battery
      systems.

PMID- 30189576
TI  - Estimating population exposure to phthalate esters in major Chinese cities
      through wastewater-based epidemiology.
AB  - Phthalate esters (PAEs) are widely used in consumer and industrial products and
      may thus pose significant health risks. Urine analysis, which has usually been
      applied to assess the health risks of PAEs, has the drawback of small sample
      sizes and insufficient representativeness. Wastewater-based epidemiology (WBE)
      collects wastewater samples containing urine from the entire community and thus
      is more representative than urine samples. In this work, exposure levels and
      health risks of PAEs were estimated on a national scale for the first time
      through the WBE approach. Wastewater samples were collected from 54 wastewater
      treatment plants in 27 major cities that cover all of the geographic regions of
      China. The estimated ?5PAEs exposure levels ranged from 290 MUg/inh/d (Lhasa) to
      3642 +/- 467 MUg/inh/d (Zhengzhou) with a mean level of 2184 +/- 1173 MUg/inh/d.
      Di-n-butyl phthalate accounted for the highest proportion (65%) in the total
      exposure level. The ?5PAEs exposure levels in Southwest China were significantly
      lower than those in other regions due to the low production and consumption of
      plastics in the region. The health risks of PAEs were assessed by comparing the
      estimated daily exposure levels to the acceptable daily exposure levels. For
      adults, the hazard index that represents cumulative risk of PAEs was above or
      below 1 depending on a particular reference dose (total daily intake values or
      the reference dose for anti-androgenicity) that was used for risk calculation. In
      contrast, the hazard index was above 1 for a significant number of cities for
      children, regardless of which reference dose was used. The results indicate that
      health risks of PAE exposure in China cannot be overlooked. Children in China are
      under considerably greater risks than adults, which warrants further research or
      proper regulation of PAE use in China.

PMID- 30189577
TI  - Integrated assessment of the climate and landuse change impact on hydrology and
      water quality in the Songkhram River Basin, Thailand.
AB  - The livelihoods of people in the Songkhram River Basin (SRB) rely heavily on
      river water, especially those involved in the fisheries. Extensive landuse
      changes in SRB have raised concerns regarding its impacts in water quality in
      addition to the looming climate change effects. More importantly there is lack of
      detailed studies on landuse and climate change impact on river water quality for
      the sustainable water management. Therefore, this study aimed at quantifying the
      individual and integrated impact of climate and landuse change in streamflows and
      nitrate nitrogen loadings in the Songkhram River. Future streamflow was simulated
      using Soil and Water Assessment Tool (SWAT) whereas future climate projections
      were derived from three Regional Climate Models (RCMs) under two Representative
      Concentration Pathways (RCPs). A dynamic, spatially explicit, land use change
      model (Dyna-CLUE) was used to generate two future land use change scenarios
      namely economic and conservation scenarios. The results show that in future
      climate change is to be responsible for a 19.5 and 24% decrease in streamflow and
      11.25 and 15.25% decrease in nitrate nitrogen loading as projected under RCP 4.5
      and 8.5 scenarios, respectively. Whereas landuse change is found to be
      responsible for a 5.30 and 6.35% increase in streamflow and an 11 and 11.60%
      decrease in nitrate nitrogen loading under economic and conservation scenarios,
      respectively in future. Thus, in conjunction, these two agents are seen to play
      against each other, creating a net effect of decreased future streamflow (16% on
      average); whereas, in the case of nitrate nitrogen loading, the two work in
      tandem, leading to an amplified reduction (24.50% on average). Although landuse
      change is found to be the less afflicting agent, its role should not be
      overlooked-it may very well further exacerbate the situation if there is a
      greater unfavourable climatic variation than projected.

PMID- 30189578
TI  - Sociodemographic predictors of residents worry about contaminated sites.
AB  - The management and remediation of contaminated environments increasingly involves
      engagement with affected local residents. Of late, risk communication tools and
      guidelines have drawn attention to the stress and concern of residents as a
      result of heightened awareness of localised contamination and the need to address
      these less visible impacts of contamination when engaging with affected
      communities. Despite this emerging focus, there is an absence of research
      exploring the factors that predict resident worry about neighbourhood
      contamination. This paper aims to address this shortcoming by drawing on data
      from a cross-sectional survey of 2009 adult residents in neighbourhoods near 13
      contaminated sites across Australia. Analyses used ordered logistic regression to
      determine the sociodemographic, environmental, and knowledge-based factors that
      influence residents' degree of worry. The findings suggest age, gender and income
      significantly affect residents' degree of worry. Being knowledgeable about the
      contaminant was associated with lower degrees of worry. Conversely, having a
      stronger sense of place within a neighbourhood predicted higher degrees of worry.
      Type of contaminant also impacted resident worry, with residents being less
      likely to worry about hydrocarbon, asbestos and waste than other types of
      contaminants. Our analyses suggest resident worry can be reduced through
      improving access to accurate information and the development of specific risk
      reduction strategies tailored to each neighbourhood and aimed at the
      heterogeneous distribution of worry amongst residential populations.

PMID- 30189579
TI  - Surface and passive/active air mould sampling: A testing exercise in a North
      London housing estate.
AB  - Despite indoor mould being one of the most common problems in residential
      properties in the UK, there are not any widely accepted methodologies for its
      measurement. This paper focusses on this problem of measurement and reports on
      the findings from a rigorous testing scheme carried out to quantify air and
      surface mould concentrations and particle counts within 71 rooms from 64
      properties in North London, some with and some without visible mould. The aim was
      to investigate the potential of passive and active air sampling strategies
      (sampling from still and actively mixed air, respectively) to explain visible
      mould, and understand how home/room characteristics correlate with the obtained
      readings. Airborne mould levels were quantified using an Andersen sampler
      (passively and actively), as well as by a chemical method based on the
      quantification of the N-acetylhexosaminidase (NAHA) activity (actively), which
      was also used to quantify surface mould. The mould levels were then correlated
      against physical characteristics of the tested homes/rooms, collected by means of
      survey sheets developed as part of this study. The findings did not reveal any
      independent variable governing all or most of the response variables, but a
      complex analysis suggested that whether it is a house or a flat could depict
      mould levels in the air and on the surfaces. It was also shown that a robust
      testing protocol should combine air and surface based methods, and an active air
      sampling strategy leads to a more accurate appraisal of airborne mould levels.
      Finally, the results showed that while there is some correlation between visible
      mould (and other moisture induced problems such as condensation) and measured air
      mould concentrations, lack of visible mould within a room does not necessarily
      mean low air mould concentrations, and thus one should not rely solely on visual
      inspection.

PMID- 30189581
TI  - The cumulative impacts of small reservoirs on hydrology: A review.
AB  - The number of small reservoirs has increased due to their reduced cost, the
      availability of many favourable locations, and their easy access due to
      proximity. The cumulative impacts of such small reservoirs are not easy to
      estimate, even when solely considering hydrology, which is partially due to the
      difficulty in collecting data on the functioning of such reservoirs. However,
      there is evidence indicating that the cumulative impacts of such reservoirs are
      significant. The aim of this article is to present a review of the studies that
      address the cumulative impacts of small reservoirs on hydrology, focusing on the
      methodology and on the way in which these impacts are assessed. Most of the
      studies addressing the hydrological cumulative impacts focused on the annual
      stream discharge, with decreases ranging from 0.2% to 36% with a mean value of
      13.4% +/- 8% over approximately 30 references. However, it is shown that similar
      densities of small reservoirs can lead to different impacts on stream discharge
      in different regions. This result is probably due to the hydro-climatic
      conditions and makes defining simple indicators to provide a first guess of the
      cumulative impacts difficult. The impacts also vary in time, with a more intense
      reduction in the river discharge during the dry years than during the wet years.
      This finding is certainly an important point to take into consideration in the
      context of climate change. Two methods are mostly used to estimate cumulative
      impacts: i) exclusively data-based methods and ii) models. The assumptions,
      interests and shortcomings of these methods are presented. Scientific tracks are
      proposed to address the four main shortcomings, namely the estimation of the
      associated uncertainties, the lack of knowledge on reservoir characteristics and
      water abstraction and the accuracy of the impact indicators.

PMID- 30189580
TI  - A dynamic transport model for quantification of norovirus internalization in
      lettuce from irrigation water and associated health risk.
AB  - Food production using recycled wastewater offers a sustainable way forward in
      light of limited freshwater resources. However, concerns of food safety should be
      addressed to protect public health. To this end, we developed a dynamic transport
      model to track norovirus from the irrigation water to the root and shoot of
      lettuce during the growth period. These processes were embodied in a system of
      ordinary differential equations that also incorporated plant growth,
      transpiration rate, viral attachment and detachment to culture media, viral
      decay, and plant barrier effects. Model parameters were either obtained from the
      literature or through fitting the model to experimental data from a study
      reporting human norovirus transport in hydroponically grown lettuce. The results
      showed that lettuce grown hydroponically resulted in a higher risk than lettuce
      grown in soil. In both cases, the risk predicted failed to meet the risk
      benchmarks established by the U.S. EPA and WHO. Viral attachment to growth media,
      such as the soil particles, was an important mechanism for risk reduction. A
      sensitivity analysis revealed that harvesting time and irrigation time are
      important factors influencing the viral loads in lettuce. Hence, this pathogen
      transport model provides a framework for investigating the effects of time and
      other factors on disease burdens from water reuse in agriculture, underscoring
      the utility of a dynamic model. In the absence of a routine monitoring of
      contaminants in the recycled irrigation water and food crops, a quantitative risk
      assessment based on objective scientific knowledge is the best approach to guide
      the policy decisions on water reuse practices.

PMID- 30189582
TI  - An optimized sample treatment method for the determination of antibiotics in
      seawater, marine sediments and biological samples using LC-TOF/MS.
AB  - Antibiotics used in marine aquaculture have been reported to accumulate in
      sediments and non-target aquatic organisms, modifying the biodiversity and the
      environmental conditions in areas close to the fish farms. Improved analytical
      methods are required to assess the spread and the impacts of aquaculture
      antibiotics in the marine environment, as well as to estimate resistance
      development risks. In this study, we have optimized a method for simultaneous
      quantitative determination of oxytetracycline, florfenicol and flumequine in
      marine samples using liquid chromatography coupled to time-of-flight high
      resolution mass spectrometry (LC-TOF/MS). The method optimization was carried out
      for seawater, sediment and biological samples (biofilm and two benthic
      invertebrate species: Gammarus aequicauda and Monodonta articulata). Special
      attention was paid to the optimization of the extraction and purification steps,
      testing: liquid-liquid and solid-liquid extractions, the use of silica and other
      commercial sorbents' clean-up, and single and tandem solid phase extraction
      procedures. The limits of quantification (MQLs) achieved with the developed
      method are 0.1-0.5 MUg L-1 in seawater; 1-5 MUg kg-1 in marine sediments; 5-25
      MUg kg-1 in biofilm; and 100-500 MUg kg-1 in invertebrates, with good accuracy
      and precision. Method recoveries in spiked samples are 65-120% in seawater and
      sediment samples, and 63-110% in the biological samples. The method has been
      successfully implemented for the determination of antibiotic concentrations in
      sediment and invertebrate samples collected from a Mediterranean bay in south
      east Spain. These represent significant advances in the analysis of antibiotics
      in environmental samples, especially for wild marine taxa, and attend for a
      proper assessment of the environmental fate and side effects of aquaculture
      antibiotics in the marine environment.

PMID- 30189585
TI  - Validity of PowerTap P1 Pedals during Laboratory-Based Cycling Time Trial
      Performance.
AB  - The use of mobile power measuring devices has become widespread within cycling,
      with a number of manufacturers now offering power measuring pedals. This study
      aimed to investigate the validity of PowerTap P1 pedals by comparing them with
      the previously validated Wattbike ergometer. Ten trained cyclists performed three
      simulated 10-mile (16-km) time trials on a Wattbike, while using PowerTap P1
      pedals. There were no statistically significant differences (p > 0.05) between
      PowerTap P1 pedals and a Wattbike for maximum, minimum, and mean power output, or
      for maximum, minimum, and mean cadence. There were good to excellent levels of
      agreement between the PowerTap P1 pedals and Wattbike (ICC > 0.8) for all
      measured variables except minimum cadence (ICC = 0.619). This suggests that
      PowerTap P1 pedals provide a valid measurement of power output.

PMID- 30189586
TI  - The Association of the 24 Hour Distribution of Time Spent in Physical Activity,
      Work, and Sleep with Emotional Exhaustion.
AB  - Previous research identified time spent in physical activity, sleeping, and
      working as predictors of emotional exhaustion. However, this research did not
      take into account the interdependence of these time-use components. Since daily
      time is limited to 24 h, time spent in one specific activity (e.g., sleep) cannot
      be used for any other activity (e.g., physical activity). We conducted a one-week
      daily sampling study to assess the compositional effects of physical activity,
      sleep, and work on emotional exhaustion. Since the sample consisted of 104
      undergraduate students, work was operationalized as study time. Participants wore
      accelerometers for one week continuously to assess sleep and physical activity.
      Also, they filled in questionnaires on study time and emotional exhaustion every
      morning. Multilevel and compositional data analyses were conducted. The
      multilevel analysis revealed significant between- (p = 0.012) and within-level (p
      < 0.001) associations of study time with emotional exhaustion. The compositional
      approach showed that time spent in physical activity was negatively related to
      emotional exhaustion (p = 0.007), whereas time spent studying was positively
      related to emotional exhaustion (p = 0.003), relative to the remaining two time
      use components. In conclusion, our results show that emotional exhaustion is not
      only associated with work-related factors, but also with off-job physical
      activity.

PMID- 30189584
TI  - Phospholipid and Lipid Derivatives as Potential Neuroprotective Compounds.
AB  - The worldwide demographical trend is changing towards a more elderly population.
      In particular, this phenomenon is increasing the number of neurodegenerative
      disease cases (e.g., Alzheimer's disease) in advanced countries. Therefore, there
      is a fertile field for neuroprotective approaches to address this problem. A
      useful strategy to protect the membrane integrity of cells and reduce
      inflammatory processes. In this context, the neurons represent particularly
      vulnerable cells. Thus, a protection strategy should include their membrane
      preservation and improved anti-inflammatory processes. The contribution of
      phospholipid derivatives to this issue is crucial and many articles evidence
      their role in both health and disease. On the other hand, some lipids containing
      choline actively participate to increase the choline levels in the nervous
      system. It is acknowledged that the cholinergic system plays a pivotal role both
      in the central and in the peripheral nervous system. Neurons cannot synthesize
      choline, which is provided by the diet. The reuptake of ACh and its hydrolysis
      represent the principal source of choline. Therefore, to cover choline needs,
      choline-containing lipids may be used. There are different works which
      demonstrate their neuroprotective features This review article analyzes
      phospholipid and lipid derivatives that through different mechanisms are involved
      in these protective processes, although, sometimes the same molecules may behave
      as neurotoxic elements, therefore, their protective machinery should be detailed
      better.

PMID- 30189583
TI  - Beyond the Antioxidant Activity of Dietary Polyphenols in Cancer: the Modulation
      of Estrogen Receptors (ERs) Signaling.
AB  - The potential "health benefits" of dietary polyphenols have been ascribed to
      their direct antioxidant activity and their impact on the regulation of cell and
      tissue redox balance. However, because of the relative poor bioavailability of
      many of these compounds, their effects could not be easily explained by the
      antioxidant action, which may occur only at high circulating and tissue
      concentrations. Therefore, many efforts have been put forward to clarify the
      molecular mechanisms underlining the biological effect of polyphenols in
      physiological and pathological conditions. Polyphenols' bioavailability,
      metabolism, and their effects on enzyme, membrane, and/or nuclear receptors and
      intracellular transduction mechanisms may define the overall impact of these
      compounds on cancer risk and progression, which is still debated and not yet
      clarified. Polyphenols are able to bind to estrogen receptor alpha (ERalpha) and
      beta (ERbeta), and therefore induce biological effects in human cells through
      mimicking or inhibiting the action of endogenous estrogens, even at low
      concentrations. In this work, the role and effects of food-contained polyphenols
      in hormone-related cancers will be reviewed, mainly focusing on the different
      polyphenols' mechanisms of action with particular attention on their estrogen
      receptor-based effects, and on the consequences of such processes on tumor
      progression and development.

PMID- 30189589
TI  - Separation and Analysis of Aspirin and Metformin HCl Using Green Subcritical
      Water Chromatography.
AB  - Organic solvents are widely used in pharmaceutical and chemical industry for
      chromatographic separations. In recent years, subcritical water chromatography
      (SBWC) has shown ability in replacing hazardous organic solvents used in
      traditional high-performance liquid chromatography (HPLC). In this work, a pain
      killer-aspirin-and an antidiabetic drug-metformin HCl-were successfully separated
      on an XBridge C18 column using no organic solvents in the subcritical water
      chromatography mobile phase. Both traditional HPLC and subcritical water
      chromatography were used for comparison purposes. SBWC separation of metformin
      HCl and aspirin were achieved at 95  degrees C and 125  degrees C, respectively.
      The recovery for both active pharmaceutical ingredients (APIs) obtained by SBWC
      is 99% in comparing with the stated content of each drug. The relative standard
      deviation is less than 1% for SBWC assays developed in this work. This level of
      accuracy and precision achieved by SBWC is the same as that resulted by the
      traditional HPLC analysis.

PMID- 30189588
TI  - "Your Body Feels Better When You Drink Water": Parent and School-Age Children's
      Sugar-Sweetened Beverage Cognitions.
AB  - Sugar-sweetened beverages (SSBs) are a leading source of added sugar in the
      American diet. Further, ingestion of added sugars from SSBs exceeds
      recommendations. Thus, interventions that effectively reduce SSB consumption are
      needed. Focus group discussions with parents (n = 37) and school-aged children
      between the ages of 6 and 11 years (n = 41) from Florida, New Jersey, and West
      Virginia were led by trained moderators using Social Cognitive Theory as a guide.
      Trends and themes that emerged from the content analysis of the focus group data
      indicated that both parents and children felt that limiting SSBs was important to
      health and weight control. However, parents and children reported consuming an
      average of 1.85 +/- 2.38 SD and 2.13 +/- 2.52 SD SSB servings/week, respectively.
      Parents and children were aware that parent behaviors influenced kids, but
      parents reported modeling healthy SSB behaviors was difficult. Busy schedules,
      including more frequent parties and events as children get older, were another
      barrier to limiting SSBs. Parents were most successful at limiting SSBs when they
      were not in the house. This qualitative research provides novel insights into
      parents' and children's cognitions (e.g., beliefs, attitudes), barriers, and
      facilitators related to SSB ingestion. Consideration of these insights during
      nutrition intervention development has the potential to improve intervention
      effectiveness in reducing SSB intake.

PMID- 30189590
TI  - Flavonoid-Rich Extract of Actinidia macrosperma (A Wild Kiwifruit) Inhibits
      Angiotensin-Converting Enzyme In Vitro.
AB  - Increasing interest in flavonoids in kiwifruit is due to the health-promoting
      properties of these bioactives. Inhibition of the angiotensin-converting enzyme
      (ACE) is one of the main therapeutic targets in controlling hypertension. The
      present study investigated the ACE inhibitory activity of flavonoid-rich extracts
      obtained from different kiwifruit genotypes. The flavonoid-rich extracts were
      prepared from fruits of Actinidia macrosperma, Actinidia deliciosa cv Hayward
      (Green kiwifruit), and Actinidia chinensis cv Hort 16A (Gold kiwifruit) by
      steeping the lyophilized fruit samples in 70% aqueous acetone, followed by
      partitioning the crude extracts with hexane. The composition of each extract was
      analyzed using ultrahigh-performance liquid chromatography-mass spectrometry
      (UPLC-MS/MS). The ACE inhibitory activity of the fruit extracts was performed
      using a fluorescence-based biochemical assay. The subclass flavonol was the most
      abundant group of flavonoids detected in all the extracts tested from three
      different kiwifruit cultivars. Quercetin-3-O-galactoside, quercetin-3-O
      glucoside, quercetin-3-O-rhamnoside, quercetin-3-O-rutinoside, quercetin-3-O
      arabinoglucoside, catechin, epigallocatechin gallate, epigallocatechin,
      chlorogenic, ferulic, isoferulic, and caffeic acid were prominent phenolics found
      in A. macrosperma kiwifruit. Overall, the flavonoid-rich extract from A.
      macrosperma showed a significantly (p < 0.05) high percentage of inhibition (IC50
      = 0.49 mg/mL), and enzyme kinetic studies suggested that it inhibits ACE activity
      in vitro. The kiwifruit extracts tested were found to be moderately effective as
      ACE inhibitors in vitro when compared to the other plant extracts reported in the
      literature. Further studies should be carried out to identify the active
      compounds from A. macrosperma and to validate the findings using experimental
      animal models of hypertension.

PMID- 30189587
TI  - Why Are Algal Viruses Not Always Successful?
AB  - Algal viruses are considered to be key players in structuring microbial
      communities and biogeochemical cycles due to their abundance and diversity within
      aquatic systems. Their high reproduction rates and short generation times make
      them extremely successful, often with immediate and strong effects for their
      hosts and thus in biological and abiotic environments. There are, however,
      conditions that decrease their reproduction rates and make them unsuccessful with
      no or little immediate effects. Here, we review the factors that lower viral
      success and divide them into intrinsic-when they are related to the life cycle
      traits of the virus-and extrinsic factors-when they are external to the virus and
      related to their environment. Identifying whether and how algal viruses adapt to
      disadvantageous conditions will allow us to better understand their role in
      aquatic systems. We propose important research directions such as experimental
      evolution or the resurrection of extinct viruses to disentangle the conditions
      that make them unsuccessful and the effects these have on their surroundings.

PMID- 30189591
TI  - A Flexible Wireless Sensor Network Based on Ultra-Wide Band Technology for Ground
      Instability Monitoring.
AB  - An innovative wireless sensor network (WSN) based on Ultra-Wide Band (UWB)
      technology for 3D accurate superficial monitoring of ground deformations, as
      landslides and subsidence, is proposed. The system has been designed and
      developed as part of an European Life+ project, called Wi-GIM (Wireless Sensor
      Network for Ground Instability Monitoring). The details of the architecture, the
      localization via wireless technology and data processing protocols are described.
      The flexibility and accuracy achieved by the UWB two-way ranging technique is
      analysed and compared with the traditional systems, such as robotic total
      stations (RTSs) and Ground-based Interferometric Synthetic Aperture Radar (GB
      InSAR), highlighting the pros and cons of the UWB solution to detect the surface
      movements. An extensive field trial campaign allows the validation of the system
      and the analysis of its sensitivity to different factors (e.g., sensor nodes
      inter-visibility, effects of the temperature, etc.). The Wi-GIM system represents
      a promising solution for landslide monitoring and it can be adopted in
      combination with traditional systems or as an alternative in areas where the
      available resources are inadequate. The versatility, easy/fast deployment and
      cost-effectiveness, together with good accuracy, make the Wi-GIM system a
      possible solution for municipalities that cannot afford expensive/complex systems
      to monitor potential landslides in their territory.

PMID- 30189592
TI  - Key Factors Influencing the Incidence of West Nile Virus in Burleigh County,
      North Dakota.
AB  - The city of Bismarck, North Dakota has one of the highest numbers of West Nile
      Virus (WNV) cases per population in the U.S. Although the city conducts extensive
      mosquito surveillance, the mosquito abundance alone may not fully explain the
      occurrence of WNV. Here, we developed models to predict mosquito abundance and
      the number of WNV cases, independently, by statistically analyzing the most
      important climate and virus transmission factors. An analysis with the mosquito
      model indicated that the mosquito numbers increase during a warm and humid summer
      or after a severely cold winter. In addition, river flooding decreased the
      mosquito numbers. The number of WNV cases was best predicted by including the
      virus transmission rate, the mosquito numbers, and the mosquito feeding pattern.
      This virus transmission rate is a function of temperature and increases
      significantly above 20  degrees C. The correlation coefficients (r) were 0.910
      with the mosquito-population model and 0.620 with the disease case model. Our
      findings confirmed the conclusions of other work on the importance of climatic
      variables in controlling the mosquito numbers and contributed new insights into
      disease dynamics, especially in relation to extreme flooding. It also suggested a
      new prevention strategy of initiating insecticides not only based on mosquito
      numbers but also 10-day forecasts of unusually hot weather.

PMID- 30189593
TI  - Longitudinal Variation of Amino Acid Levels in Human Milk and Their Associations
      with Infant Gender.
AB  - It is discussed that specific amino acids (AAs) have functional roles in early
      life. Understanding the AA composition in human milk (HM) during lactation
      assists in specifying these roles. To this end we assessed the levels of free AAs
      (FAAs), total AAs (free and bound, TAAs) and protein levels in HM in the first 6
      months of lactation, and evaluated possible associations with infant gender. HM
      samples of 25 healthy Dutch mothers participating in the PreventCD study were
      collected monthly during the first 6 months of lactation. Of the participating
      mothers, 12 gave birth to a boy and 13 gave birth to a girl. Analyses of the HM
      samples revealed that levels of free glutamate, glutamine, aspartate, glycine,
      and serine significantly increased during months 1-3 of lactation, both in
      absolute sense and relative to TAA levels. Evaluation of gender differences by
      mixed model analyses revealed an association between female infant gender and
      higher protein content (p = 0.0465) and TAA content (p = 0.0362) in HM during the
      first 3 months of lactation. Furthermore, there was a tendency for an association
      of male infant gender with higher levels of free glutamine (p = 0.0948) in HM
      during the first 3 months of lactation. These results show that FAA, TAA and
      protein levels in HM display a time-specific occurrence during lactation.
      Moreover, although confirmation is necessary in view of the small sample size,
      this study indicates that the AA composition in HM shows differential effects of
      the infant's sex.

PMID- 30189595
TI  - Structural Architectural Features of Cyclodextrin Oligoesters Revealed by
      Fragmentation Mass Spectrometry Analysis.
AB  - Cyclodextrins (CDs) were used in the present study for the ring-opening
      oligomerization (ROO) of l-lactide (LA) in order to synthesize biodegradable
      products with possible applications in pharmaceutical and medical fields. The
      practical importance of ROO reactions may reside in the possibility of
      synthesizing novel CD derivatives with high purity due to the dual role played by
      CDs, the role of the initiator through the hydroxylic groups, and the role of the
      catalyst by monomer inclusion in the CD cavity. The analyzed compounds were CDs
      modified with oligolactides obtained through ROO reactions of l-lactide in
      dimethylformamide. The resulting CD isomeric mixtures were investigated using
      classical characterization techniques such as gel permeation chromatography and
      nuclear magnetic resonance. Moreover, advanced mass spectrometry (MS) techniques
      were employed for the determination of the average number of monomer units
      attached to the cyclodextrin and the architecture of the derivatives (if the
      monomer units were attached as a single chain or as multiple chains). Thus,
      fragmentation studies effectuated on two different instruments (ESI Q-TOF and
      MALDI TOF) allowed us to correlate the size of the oligolactide chains attached
      to the CD with the observed fragmentation patterns.

PMID- 30189596
TI  - Hypoglycemic Efficacy of Docking Selected Natural Compounds against alpha
      Glucosidase and alpha-Amylase.
AB  - The inhibition of alpha-glucosidase and alpha-amylase is a clinical strategy for
      the treatment of type II diabetes, and herbal medicines have been reported to
      credibly alleviate hyperglycemia. Our previous study has reported some
      constituents from plant or herbal sources targeted to alpha-glucosidase and alpha
      amylase via molecular docking and enzymatic measurement, but the hypoglycemic
      potencies in cell system and mice have not been validated yet. This study was
      aimed to elucidate the hypoglycemic efficacy of docking selected compounds in
      cell assay and oral glucose and starch tolerance tests of mice. All test
      compounds showed the inhibition of alpha-glucosidase activity in Caco-2 cells.
      The decrease of blood sugar levels of test compounds in 30 min and 60 min of mice
      after OGTT and OSTT, respectively and the decreased glucose levels of test
      compounds were significantly varied in acarbose. Taken altogether, in vitro and
      in vivo experiments suggest that selected natural compounds (curcumin,
      antroquinonol, HCD, docosanol, tetracosanol, rutin, and actinodaphnine) via
      molecular docking were confirmed as potential candidates of alpha-glucosidase and
      alpha-amylase inhibitors for treating diabetes.

PMID- 30189594
TI  - Whole Genome Analysis of Cyclin Dependent Kinase (CDK) Gene Family in Cotton and
      Functional Evaluation of the Role of CDKF4 Gene in Drought and Salt Stress
      Tolerance in Plants.
AB  - Cotton (Gossypium spp.) is the number one crop cultivated for fiber production
      and the cornerstone of the textile industry. Drought and salt stress are the
      major abiotic stresses, which can have a huge economic impact on cotton
      production; this has been aggravated with continued climate change, and
      compounded by pollution. Various survival strategies evolved by plants include
      the induction of various stress responsive genes, such as cyclin dependent
      kinases (CDKs). In this study, we performed a whole-genome identification and
      analysis of the CDK gene family in cotton. We identified 31, 12, and 15 CDK genes
      in G. hirsutum, G. arboreum, and G. raimondii respectively, and they were
      classified into 6 groups. CDK genes were distributed in 15, 10, and 9 linkage
      groups of AD, D, and A genomes, respectively. Evolutionary analysis revealed that
      segmental types of gene duplication were the primary force underlying CDK genes
      expansion. RNA sequence and RT-qPCR validation revealed that Gh_D12G2017 (CDKF4)
      was strongly induced by drought and salt stresses. The transient expression of
      Gh_D12G2017-GFP fusion protein in the protoplast showed that Gh_D12G2017 was
      localized in the nucleus. The transgenic Arabidopsis lines exhibited higher
      concentration levels of the antioxidant enzymes measured, including peroxidase
      (POD), superoxide dismutase (SOD), and catalase (CAT) concentrations under
      drought and salt stress conditions with very low levels of oxidants. Moreover,
      cell membrane stability (CMS), excised leaf water loss (ELWL), saturated leaf
      weight (SLW), and chlorophyll content measurements showed that the transgenic
      Arabidopsis lines were highly tolerant to either of the stress factors compared
      to their wild types. Moreover, the expression of the stress-related genes was
      also significantly up-regulated in Gh_D12G2017(CDKF4) transgenic Arabidopsis
      plants under drought and salt conditions. We infer that CDKF-4s and CDKG-2s might
      be the primary regulators of salt and drought responses in cotton.

PMID- 30189597
TI  - Effect of Adherence to a Mediterranean Diet and Olive Oil Intake during Pregnancy
      on Risk of Small for Gestational Age Infants.
AB  - To quantify the effect of a Mediterranean dietary pattern, as well as the
      consumption of olive oil (OO), on the risk of having a small for gestational age
      infants (SGA), a matched case-control study was conducted in Spain. Dietary
      intake during pregnancy was assessed using a validated food frequency
      questionnaire. Three indices were used to evaluate the adherence to Mediterranean
      diet (MD) (Predimed, Trichopoulou and Panagiotakos). Crude odds ratios (cOR) and
      adjusted odds ratios (aOR) and their 95% confidence intervals (CI) were estimated
      using conditional logistic regression models. Results were stratified by severity
      of SGA: moderate (percentiles 6-10), and severe (percentiles <=5). For moderate,
      four or more points in the Predimed's index was associated with a 41% reduction
      of having SGA compared with women with a score <=3, aOR = 0.59 (95% CI 0.38
      0.98); for severe, the reduction in risk was not statistically significant.
      Similar results were found when the other MD indexes were used. An intake of OO
      above 5 g/day was associated with a lower risk of SGA (aOR = 0.53, 95% CI 0.34
      0.85); statistical significance was observed for moderate SGA (aOR = 0.53, 95% CI
      0.30-0.96), but not for severe SGA (aOR = 0.51, 95% CI 0.24-1.07), although the
      magnitude of ORs were quite similar. Adherence to a MD and OO intake is
      associated with a reduced risk of SGA.

PMID- 30189600
TI  - Innovations in Women's Bone Health-Appreciating Important "Bone Variables"
      Besides Estrogen.

PMID- 30189601
TI  - Effects of Pure and Mixed Autochthonous Torulaspora delbrueckii and Saccharomyces
      cerevisiae on Fermentation and Volatile Compounds of Narince Wines.
AB  - The cultivar of Narince is a native white grape variety of Vitis vinifera, grown
      in Tokat city, the Mid-Black Sea Region of Anatolia. In this study, the effects
      of pure and mixed autochthonous Torulaspora delbrueckii-214 and Saccharomyces
      cerevisiae-1088 cultures on the fermentation behavior and aroma compounds of
      Narince wines were investigated. Volatile compounds formed in wines were
      extracted using a liquid-liquid extraction method and determined by GC-MS-FID.
      Narince grape must was fermented in duplicate, under the following three
      conditions. Two pure cultures of T. delbrueckii-214 and S. cerevisiae-1088 and a
      mixture of T. delbrueckii-214 and S. cerevisiae-1088 (1:1). The presence of the
      non-Saccharomyces T. delbrueckii-214 yeast slowed down the fermentation and
      produced a lower level of ethanol and a higher levels of glycerol and volatile
      acid. Only the pure culture of T. delbrueckii-214 was unable to finish
      fermentation. On the other hand, mixed culture fermentation improved the aroma
      intensity and complexity of wine due to increased levels of higher alcohols and
      esters. According to sensory analysis, wine fermented with mixed culture was the
      most preferred wine followed by wine inoculated with pure S. cerevisiae-1088.
      This study confirms the role of T. delbrueckii in wine aroma and the potential of
      non-Saccharomyces use in winemaking.

PMID- 30189599
TI  - Metabolic and Biosynthetic Diversity in Marine Myxobacteria.
AB  - Prior to 2005, the vast majority of characterized myxobacteria were obtained from
      terrestrial habitats. Since then, several species of halotolerant and even
      obligate marine myxobacteria have been described. Chemical analyses of extracts
      from these organisms have confirmed their ability to produce secondary
      metabolites with unique chemical scaffolds. Indeed, new genera of marine-derived
      myxobacteria, particularly Enhygromyxa, have been shown to produce novel chemical
      scaffolds that differ from those observed in soil myxobacteria. Further studies
      have shown that marine sponges and terrestrial myxobacteria are capable of
      producing similar or even identical secondary metabolites, suggesting that
      myxobacterial symbionts may have been the true producers. Recent in silico
      analysis of the genome sequences available from six marine myxobacteria disclosed
      a remarkably versatile biosynthetic potential. With access to ever-advancing
      tools for small molecule and genetic evaluation, these studies suggest a bright
      future for expeditions into this yet untapped resource for secondary metabolites.

PMID- 30189598
TI  - Exosomal Chaperones and miRNAs in Gliomagenesis: State-of-Art and Theranostics
      Perspectives.
AB  - Gliomas have poor prognosis no matter the treatment applied, remaining an unmet
      clinical need. As background for a substantial change in this situation, this
      review will focus on the following points: (i) the steady progress in
      establishing the role of molecular chaperones in carcinogenesis; (ii) the recent
      advances in the knowledge of miRNAs in regulating gene expression, including
      genes involved in carcinogenesis and genes encoding chaperones; and (iii) the
      findings about exosomes and their cargo released by tumor cells. We would like to
      trigger a discussion about the involvement of exosomal chaperones and miRNAs in
      gliomagenesis. Chaperones may be either targets for therapy, due to their tumor
      promoting activity, or therapeutic agents, due to their antitumor growth
      activity. Thus, chaperones may well represent a Janus-faced approach against
      tumors. This review focuses on extracellular chaperones as part of exosomes'
      cargo, because of their potential as a new tool for the diagnosis and management
      of gliomas. Moreover, since exosomes transport chaperones and miRNAs (the latter
      possibly related to chaperone gene expression in the recipient cell), and
      probably deliver their cargo in the recipient cells, a new area of investigation
      is now open, which is bound to generate significant advances in the understanding
      and treatment of gliomas.

PMID- 30189603
TI  - Correction: Control of the Size of Silver Nanoparticles and Release of Silver in
      Heat Treated SiO2-Ag Composite Powders. Materials 2018, 11, 80.
AB  - In the published article "Control of the Size of Silver Nanoparticles and Release
      of Silver in Heat Treated SiO2-Ag Composite Powders" [1] a reference was omitted
      in the caption of Figure 4b. [...].

PMID- 30189602
TI  - Rural Versus Urban Patients: Benchmarking the Outcomes of Patients with Acute
      Myocardial Infarction in Shanxi, China from 2013 to 2017.
AB  - Rural-urban disparity in China attracts special international attention in view
      of the imbalance of economic development between rural and urban areas. However,
      few studies used patient level data to explore the disparity of health outcomes
      between rural and urban patients. This study aims to evaluate the trend of health
      outcomes between rural and urban patients hospitalized with acute myocardial
      infarction (AMI) in China. Using an electronic medical records (EMRs) database in
      Shanxi, China, we identified 87,219 AMI patients hospitalized between 2013 and
      2017. We used multivariable binary logistic regressions and two-part models to
      estimate the association between region of origin (rural/urban) and two outcomes,
      in-hospital mortality and out-of-pocket (OOP) expenses. Rural patients were
      associated with lower in-hospital mortality and the adjusted Odds Ratios (ORs)
      were 0.173, 0.34, 0.605, 0.522, 0.556 (p-values < 0.001) from 2013 to 2017,
      respectively. For the OOP expenses, rural patients were experiencing increasing
      risk of having OOP expenses, with the ORs of 0.159, 0.573, 1.278, 1.281, 1.65.
      The coefficients for the log-linear models in the five years were 0.075 (p =
      0.352), 0.61, 0.565, 0.439, 0.46 (p-values < 0.001). Policy makers in China
      should notice and narrow the gap of health outcomes between rural and urban
      patients.

PMID- 30189605
TI  - A Novel Fluorescent Biosensor for Adenosine Triphosphate Detection Based on a
      Metal-Organic Framework Coating Polydopamine Layer.
AB  - In this work, a novel and sensitive fluorescent biosensor based on polydopamine
      coated Zr-based metal-organic framework (PDA/UiO-66) is presented for adenosine
      triphosphate (ATP) detection. This PDA/UiO-66 nanoparticle which holds a great
      potential to be excellent fluorescence quencher can protect the 6
      carboxyfluorescein (FAM)-labeled probe from cleaved by DNase I dispersed in
      solution and the flurescence of labeled FAM is quenched. When ATP molecules
      exist, aptamers on the PDA/UiO-66 nanoparticles can hybridize with ATP molecule
      to form complex structure that will be desorbed from the PDA/UiO-66 and digested
      by DNase I. After that, the released ATP molecule can react with another aptamer
      on the PDA/UiO-66 complexes, then restarts a new cycle. Herein, the excellent
      strong fluorescence quenching ability and uploading more amount of aptamer probes
      of PDA/UiO-66 composites make them efficient biosensors, leading to a high
      sensitivity with detection limit of 35 nM. Compared with ATP detection directly
      by UiO-66-based method, the LOD is about 5.7 times higher with PDA/UiO-66
      nanoparticle. Moreover, the enhanced biocompatibility and bioactivity with PDA
      layer of the composites render a proposed strategy for clinical diagnosis field
      of detecting small biological molecules in vivo in the future.

PMID- 30189606
TI  - Chemometric Comparison and Classification of Some Essential Oils Extracted from
      Plants Belonging to Apiaceae and Lamiaceae Families Based on Their Chemical
      Composition and Biological Activities.
AB  - This study is focused on the comparison and classification of parsley, lovage,
      basil, and thyme essential oils (EOs) based on their chemical composition, total
      phenolic content, antioxidant and antibacterial activities by using appropriate
      chemometric methods: Principal component analysis (PCA) and hierarchical cluster
      analysis (HCA). The results showed that parsley, lovage, and thyme EOs are rich
      in monoterpene hydrocarbons, but basil EO is rich in oxygenated monoterpenes and
      phenylpropanoids, and that both PCA and HCA separated essential oils into two
      main groups of which one contains two sub-groups. beta-Phellandrene was the major
      component identified in parsley and lovage EOs, estragole was the major component
      in basil EO, and p-cymene was the major component in thyme EO. Thyme EO showed
      the highest level of total phenolics, the highest antioxidant capacity, and
      exhibited the stronger antibacterial activity, results that were emphasized by
      both chemometric methods used. Among tested essential oils, the one of parsley
      was distinguished by a low total TPC, weak antioxidant activity, and weak
      antibacterial activity against S. enteritidis (ATCC 13076); lovage EO by low TPC,
      weak antioxidant activity, but moderate antibacterial activity; and basil EO by
      low TPC, moderate antioxidant activity, and weak antibacterial activity against
      L. monocytogenes (ATCC 19114).

PMID- 30189604
TI  - Host Shutoff in Influenza A Virus: Many Means to an End.
AB  - Influenza A virus carries few of its own proteins, but uses them effectively to
      take control of the infected cells and avoid immune responses. Over the years,
      host shutoff, the widespread down-regulation of host gene expression, has emerged
      as a key process that contributes to cellular takeover in infected cells.
      Interestingly, multiple mechanisms of host shutoff have been described in
      influenza A virus, involving changes in translation, RNA synthesis and stability.
      Several viral proteins, notably the non-structural protein NS1, the RNA-dependent
      RNA polymerase and the endoribonuclease PA-X have been implicated in host
      shutoff. This multitude of host shutoff mechanisms indicates that host shutoff is
      an important component of the influenza A virus replication cycle. Here we review
      the various mechanisms of host shutoff in influenza A virus and the evidence that
      they contribute to immune evasion and/or viral replication. We also discuss what
      the purpose of having multiple mechanisms may be.

PMID- 30189607
TI  - The Association between US Adolescents' Weight Status, Weight Perception, Weight
      Satisfaction, and Their Physical Activity and Dietary Behaviors.
AB  - Background: It remain unclear that the association between weight status, weight
      perception, weight satisfaction and the clustering of physical activity (PA) and
      dietary behaviors in adolescents. Method: A cross-sectional analysis of National
      Health and Nutrition Examination Survey and the US Department of Agriculture's
      Food Patterns Equivalents 2007-2014 data from adolescents aged 12-17 years (n =
      2965) was conducted. Multivariable logistic regression models adjusted for
      demographic characteristics examined the association between weight status,
      weight perception, weight satisfaction, and the four created lifestyle groups
      (healthier behaviors, healthier diet only, physically active only, unhealthier
      behaviors). Results: Males with obesity were more likely to be in the healthier
      diet only group than males with a normal weight (OR = 1.90, 95% CI: 1.02, 3.52).
      Similar patterns were found in males who perceived themselves as being overweight
      or having obesity (OR = 2.09, 95% CI: 1.09, 3.99) and males with obesity who
      perceived their weight status accurately (OR = 2.33, 95% CI: 1.12, 4.88). Female
      respondents who were satisfied with their weight were 59% less likely to be in
      the healthier diet only group than healthier behaviors group compared with
      females who were weight dissatisfied (OR = 0.41, 95% CI: 0.23, 0.75). This
      pattern was not observed in males. Conclusions: Clustering PA and dietary
      behaviors were associated with weight status and weight perception for males but
      not females. Weight satisfaction was associated with clustered PA and dietary
      behaviors for females. These findings are important for obesity prevention
      policies and programs to better address adolescents' obesity and reduce health
      disparities in this population.

PMID- 30189608
TI  - CDC42 Negatively Regulates Testis-Specific SEPT12 Polymerization.
AB  - Septin (SEPT) genes encode well-preserved polymerizing GTP-binding cytoskeletal
      proteins. The cellular functions of SEPTs consist of mitosis, cytoskeletal
      remodeling, cell polarity, and vesicle trafficking through interactions with
      various types of cytoskeletons. We discovered that mutated SEPTIN12 in different
      codons resulted in teratozoospermia or oligozoospermia. In mouse models with a
      defective Septin12 allele, sperm morphology was abnormal, sperm count decreased,
      and sperms were immotile. However, the regulators of SEPT12 are completely
      unknown. Some studies have indicated that CDC42 negatively regulates the
      polymerization of SEPT2/6/7 complexes in mammalian cell lines. In this study, we
      investigated whether CDC42 modulates SEPT12 polymerization and is involved in the
      terminal differentiation of male germ cells. First, through scanning electron
      microscopy analysis, we determined that the loss of Septin12 caused defective
      sperm heads. This indicated that Septin12 is critical for the formation of sperm
      heads. Second, CDC42 and SEPT12 were similarly localized in the perinuclear
      regions of the manchette at the head of elongating spermatids, neck region of
      elongated spermatids, and midpiece of mature spermatozoa. Third, wild-type CDC42
      and CDC42Q61L (a constitutive-acting-mutant) substantially repressed SEPT12
      polymerization, but CDC42T17N (a dominant-negative-acting mutant) did not, as
      evident through ectopic expression analysis. We concluded that CDC42 negatively
      regulates SEPT12 polymerization and is involved in terminal structure formation
      of sperm heads.

PMID- 30189609
TI  - Synthesis, Characterization, and Antifungal Property of Hydroxypropyltrimethyl
      Ammonium Chitosan Halogenated Acetates.
AB  - Hydroxypropyltrimethyl ammonium chitosan halogenated acetates were successfully
      synthesized from six different haloacetic acids and hydroxypropyltrimethyl
      ammonium chloride chitosan (HACC) with high substitution degree, which are
      hydroxypropyltrimethyl ammonium chitosan bromacetate (HACBA),
      hydroxypropyltrimethyl ammonium chitosan chloroacetate (HACCA),
      hydroxypropyltrimethyl ammonium chitosan dichloroacetate (HACDCA),
      hydroxypropyltrimethyl ammonium chitosan trichloroacetate (HACTCA),
      hydroxypropyltrimethyl ammonium chitosan difluoroacetate (HACDFA), and
      hydroxypropyltrimethyl ammonium chitosan trifluoroacetate (HACTFA). These
      chitosan derivatives were synthesized by two steps: first, the
      hydroxypropyltrimethyl ammonium chloride chitosan was synthesized by chitosan and
      3-chloro-2-hydroxypropyltrimethyl ammonium chloride. Then, hydroxypropyltrimethyl
      ammonium chitosan halogenated acetates were synthesized via ion exchange. The
      structures of chitosan derivatives were characterized by Fourier transform
      infrared spectroscopy (FTIR), 1H Nuclear magnetic resonance spectrometer (1H
      NMR), 13C Nuclear magnetic resonance spectrometer (13C NMR), and elemental
      analysis. Their antifungal activities against Colletotrichum lagenarium, Fusarium
      graminearum, Botrytis cinerea, and Phomopsis asparagi were investigated by hypha
      measurement in vitro. The results revealed that hydroxypropyltrimethyl ammonium
      chitosan halogenated acetates had better antifungal activities than chitosan and
      HACC. In particular, the inhibitory activity decreased in the order: HACTFA >
      HACDFA > HACTCA > HACDCA > HACCA > HACBA > HACC > chitosan, which was consistent
      with the electron-withdrawing property of different halogenated acetates. This
      experiment provides a potential idea for the preparation of new antifungal drugs
      by chitosan.

PMID- 30189610
TI  - An Empirical Analysis of the Perceived Challenges and Benefits of Introducing
      Biosimilars in Bangladesh: A Paradigm Shift.
AB  - The high demand for and resulting financial success of biopharmaceutical products
      over the last three decades have seen the door open for close copies of these
      biological products, also known as biosimilars. This paper seeks to collate all
      relevant published intelligence with acquired survey data to assess the weight of
      available evidence that these products hold immense potential for the
      pharmaceutical industry in terms of their applications and benefits. Biosimilars
      also pose to be of great promise to the Bangladesh pharmaceutical industry, with
      the commitment of drastically reducing its dependence on foreign imports of
      biopharmaceutics to meet local demand. Our questionnaire based survey involved
      100 Clinicians, 50 Industry Experts and 100 Academicians. The study found that
      majority of Industry Experts (72%) and Academicians (63%) shared a different
      concept of biosimilars opposed to majority of Clinicians (78%). Majority of
      Academicians (68%) and Industry Experts (61%) also shared a different belief from
      that of most Clinicians (61%) regarding the need for updating the existing
      regulatory guidelines. The study also showed that Clinicians (67%), Industry
      Experts (83%) and Academicians (80%) highlighted the benefit of lower costs of
      biosimilars. Furthermore, the quality data obtained from the survey results
      allowed us to evaluate and provide recommendations for stakeholders on the need
      for increased biosimilar awareness, pharmacovigilance and safety in Bangladesh.

PMID- 30189611
TI  - Poor Vitamin Status is Associated with Skeletal Muscle Loss and Mucositis in Head
      and Neck Cancer Patients.
AB  - Mucositis and muscle wasting are two common toxicity effects of cancer treatment
      in head and neck cancer (HNC). There is limited data evaluating cancer treatment
      toxicities in relation to vitamin status. This study aimed to assess changes in
      vitamin status during HNC treatment in relation to body composition, inflammation
      and mucositis. In this prospective cohort study, dietary intakes (3-day food
      record), plasma levels of vitamins and C-reactive protein (CRP) were assessed at
      baseline (at diagnosis) and post-treatment (after 6-8 weeks of radiation therapy
      with or without chemotherapy). Computed tomography images were used to quantify
      body composition. Mucositis information was collected from health records of
      patients. Twenty-eight HNC patients (age 60 +/- 10 years) completed both study
      time points. Patients who developed mucositis had significantly lower dietary
      intake of vitamins and plasma 25-hydroxy vitamin D (25-OHD) and all-trans retinol
      levels (p < 0.02). Patients lost a considerable amount of muscle mass (3.4 kg)
      and fat mass (3.6 kg) over the course of treatment. There was a trend toward
      greater muscle loss in patients with 25-OHD < 50 nmol/L compared to patients with
      25-OHD >= 50 nmol/L (p = 0.07). A significant negative correlation was found
      between plasma all-trans retinol and CRP level at the end of treatment (p =
      0.03). Poor vitamin status could be a contributing factor in developing treatment
      induced toxicities.

PMID- 30189612
TI  - Concentration of Lactoferrin in Human Milk and Its Variation during Lactation in
      Different Chinese Populations.
AB  - BACKGROUND: Lactoferrin (Lf) is a multifunctional protein and one of the most
      abundant proteins in human milk. Various factors may affect its concentration in
      human milk, such as stage of lactation, ethnicity, and diet. OBJECTIVES: The
      objectives of the present study were to examine the dynamic change in milk Lf
      throughout the course of lactation and explore factors associated with milk Lf
      concentrations in various Chinese populations. METHODS: This investigation was a
      part of a large cross-sectional study conducted in 11 provinces/autonomous
      regions/municipalities (Beijing, Gansu, Guangdong, Guangxi, Heilongjiang, Inner
      Mongolia, Shandong, Shanghai, Xinjiang, Yunnan, and Zhejiang) across China
      between 2011 and 2013. Lactating women (n = 6481) within 0-330 days postpartum
      were recruited in the original study. A sub-sample of 824 women was randomly
      selected, and milk Lf concentrations were determined by UPLC/MS. RESULTS: The Lf
      concentration in milk from women delivering at term was 3.16 g/L, 1.73 g/L and
      0.90 g/L for colostrum, transitional milk, and mature milk, respectively. Lf
      concentrations differed significantly between stages of lactation (colostrum vs.
      transitional milk, colostrum vs. mature milk, transitional milk vs. mature milk,
      all p < 0.001). Maternal BMI, age, mode of delivery, parturition, protein intake,
      and serum albumin concentration were not correlated with milk Lf concentration.
      However, milk Lf concentrations varied among different geographical regions
      (Guangdong (1.91 g/L) vs. Heilongjiang (1.44 g/L), p = 0.037; Guangdong (1.91
      g/L) vs. Gansu (1.43 g/L), p = 0.041) and ethnicities (Dai (1.80 g/L) vs. Tibetan
      (0.99 g/L), p = 0.007; Han (1.62 g/L) vs. Tibetan (0.99 g/L), p = 0.002) in
      China. CONCLUSIONS: The concentration of Lf in human milk changes dynamically
      throughout lactation. Few maternal characteristics affect the milk Lf
      concentration, but it varies across different geographical regions and
      ethnicities in China.

PMID- 30189613
TI  - Complemented Palindromic Small RNAs First Discovered from SARS Coronavirus.
AB  - In this study, we report for the first time the existence of complemented
      palindromic small RNAs (cpsRNAs) and propose that cpsRNAs and palindromic small
      RNAs (psRNAs) constitute a novel class of small RNAs. The first discovered 19-nt
      cpsRNA UUAACAAGCUUGUUAAAGA, named SARS-CoV-cpsR-19, was detected from a 22-bp DNA
      complemented palindrome TCTTTAACAAGCTTGTTAAAGA in the severe acute respiratory
      syndrome coronavirus (SARS-CoV) genome. The phylogenetic analysis supported that
      this DNA complemented palindrome originated from bat betacoronavirus. The results
      of RNA interference (RNAi) experiments showed that one 19-nt segment
      corresponding to SARS-CoV-cpsR-19 significantly induced cell apoptosis. Using
      this joint analysis of the molecular function and phylogeny, our results
      suggested that SARS-CoV-cpsR-19 could play a role in SARS-CoV infection or
      pathogenesis. The discovery of cpsRNAs has paved a way to find novel markers for
      pathogen detection and to reveal the mechanisms underlying infection or
      pathogenesis from a different point of view. Researchers can use cpsRNAs to study
      the infection or pathogenesis of pathogenic viruses when these viruses are not
      available. The discovery of psRNAs and cpsRNAs, as a novel class of small RNAs,
      also inspire researchers to investigate DNA palindromes and DNA complemented
      palindromes with lengths of psRNAs and cpsRNAs in viral genomes.

PMID- 30189614
TI  - Synthesis and Characterization of Controlled Nitric Oxide Release from S-Nitroso
      N-Acetyl-d-Penicillamine Covalently Linked to Polyvinyl Chloride (SNAP-PVC).
AB  - Polyvinyl chloride (PVC) is one of the most widely used polymers in medicine but
      has very poor biocompatibility when in contact with tissue or blood. To increase
      biocompatibility, controlled release of nitric oxide (NO) can be utilized to
      mitigate and reduce the inflammatory response. A synthetic route is described
      where PVC is aminated to a specified degree and then further modified by
      covalently linking S-nitroso-N-acetyl-d-penicillamine (SNAP) groups to the free
      primary amine sites to create a nitric oxide releasing polymer (SNAP-PVC).
      Controllable release of NO from SNAP-PVC is described using photoinitiation from
      light emitting diodes (LEDs). Ion-mediated NO release is also demonstrated as
      another pathway to provide a passive mechanism for NO delivery. The large range
      of NO fluxes obtained from the SNAP-PVC films indicate many potential uses in
      mediating unwanted inflammatory response in blood- and tissue-contacting devices
      and as a tool for delivering precise amounts of NO in vitro.

PMID- 30189615
TI  - Actin-Myosin Interaction: Structure, Function and Drug Discovery.
AB  - Actin-myosin interactions play crucial roles in the generation of cellular force
      and movement. The molecular mechanism involves structural transitions at the
      interface between actin and myosin's catalytic domain, and within myosin's light
      chain domain, which contains binding sites for essential (ELC) and regulatory
      light chains (RLC). High-resolution crystal structures of isolated actin and
      myosin, along with cryo-electron micrographs of actin-myosin complexes, have been
      used to construct detailed structural models for actin-myosin interactions.
      However, these methods are limited by disorder, particularly within the light
      chain domain, and they do not capture the dynamics within this complex under
      physiological conditions in solution. Here we highlight the contributions of site
      directed fluorescent probes and time-resolved fluorescence resonance energy
      transfer (TR-FRET) in understanding the structural dynamics of the actin-myosin
      complex in solution. A donor fluorescent probe on actin and an acceptor
      fluorescent probe on myosin, together with high performance TR-FRET, directly
      resolves structural states in the bound actin-myosin complex during its
      interaction with adenosine triphosphate (ATP). Results from these studies have
      profound implications for understanding the contractile function of actomyosin
      and establish the feasibility for the discovery of allosteric modulators of the
      actin-myosin interaction, with the ultimate goal of developing therapies for
      muscle disorders.

PMID- 30189616
TI  - Plasma Electrolytic Oxidation of Magnesium Alloy AZ31B in Electrolyte Containing
      Al2O3 Sol as Additives.
AB  - Plasma electrolytic oxidation (PEO) coatings were produced on AZ31B magnesium
      alloys in alkaline electrolytes with the addition of various concentrations of
      Al2O3 sols. Effects of Al2O3 sol concentrations on the microstructure, phase
      composition, corrosion resistance and hardness of PEO coatings were evaluated by
      scanning electron microscopy (SEM), X-ray diffraction (XRD), microhardness
      testing and potentiodynamic polarization measurements, respectively. It was
      revealed that the Al2O3 sol mostly participated in the formation of the ceramic
      coating and transferred into the MgAl2O4 phase. With the increase of the Al2O3
      sol concentration in the range of 0-6 vol%, the coating performance in terms of
      the microstructure, diffraction peak intensity of the MgAl2O4 phase, corrosion
      resistance and microhardness was improved. Further increase of Al2O3 sol addition
      did not generate better results. This indicated that 6 vol% might be the proper
      Al2O3 sol concentration for the formation of PEO coatings.

PMID- 30189617
TI  - Conformationally Restricted Peptides from Rice Proteins Elicit Antibodies That
      Recognize the Corresponding Native Protein in ELISA Assays.
AB  - The rice hoja blanca virus (RHBV), transmitted by the planthopper insect
      Tagosodes orizicolus, is a disease that attacks rice and generates significant
      production losses in Colombia. Fedearroz 2000 and Colombia I commercial rice
      varieties, which have different resistance levels to the disease, were selected
      in this study. To identify proteins associated to the insect and virus signaling,
      a comparative proteomics study was performed. By comparing proteomic profiles,
      between virus-infected and control group plants in two-dimensional
      electrophoresis, proteins exhibiting significant changes in abundance were found.
      In another test, peptide dendrimers containing sequences conformationally
      restricted to alpha-helix from four of those rice proteins were synthesized. In
      the experiment, sera from mice inoculated with peptide dendrimers could recognize
      the corresponding native protein in ELISA assays. Reported comparative proteomic
      results provide new insights into the molecular mechanisms of plant response to
      the RHBV and comprehensive tools for the analysis of new crop varieties. Besides,
      results from conformational peptide dendrimer approach are promising and show
      that it is feasible to detect proteins as markers, and may have biological
      applications by decreasing the susceptibility to proteolytic degradation.

PMID- 30189618
TI  - Thermostable Xylanase Production by Geobacillus sp. Strain DUSELR13, and Its
      Application in Ethanol Production with Lignocellulosic Biomass.
AB  - The aim of the current study was to optimize the production of xylanase, and its
      application for ethanol production using the lignocellulosic biomass. A highly
      thermostable crude xylanase was obtained from the Geobacillus sp. strain DUSELR13
      isolated from the deep biosphere of Homestake gold mine, Lead, SD. Geobacillus
      sp. strain DUSELR13 produced 6 U/mL of the xylanase with the beechwood xylan. The
      xylanase production was improved following the optimization studies, with one
      factor at a time approach, from 6 U/mL to 19.8 U/mL with xylan. The statistical
      optimization with response surface methodology further increased the production
      to 31 U/mL. The characterization studies revealed that the crude xylanase complex
      had an optimum pH of 7.0, with a broad pH range of 5.0-9.0, and an optimum
      temperature of 75  degrees C. The ~45 kDa xylanase protein was highly
      thermostable with t1/2 of 48, 38, and 13 days at 50, 60, and 70  degrees C,
      respectively. The xylanase activity increased with the addition of Cu+2, Zn+2,
      K+, and Fe+2 at 1 mM concentration, and Ca+2, Zn+2, Mg+2, and Na+ at 10 mM
      concentration. The comparative analysis of the crude xylanase against its
      commercial counterpart Novozymes Cellic HTec and Dupont, Accellerase XY, showed
      that it performed better at higher temperature, hydrolyzing 65.4% of the
      beechwood at 75  degrees C. The DUSEL R13 showed the mettle to hydrolyze, and
      utilize the pretreated, and untreated lignocellulosic biomass: prairie cord grass
      (PCG), and corn stover (CS) as the substrate, and gave a maximum yield of 20.5
      U/mL with the untreated PCG. When grown in co-culture with Geobacillus
      thermoglucosidasius, it produced 3.53 and 3.72 g/L ethanol, respectively with
      PCG, and CS. With these characteristics the xylanase under study could be an
      industrial success for the high temperature bioprocesses.

PMID- 30189619
TI  - Moderate Beer Intake and Cardiovascular Health in Overweight Individuals.
AB  - Consistent epidemiological evidence indicates that low-to-moderate alcohol
      consumption is inversely associated with cardiovascular event presentation, while
      high levels of alcohol intake are associated to increased cardiovascular risk.
      Little is known on the effects of moderate beer intake in the metabolic syndrome.
      The aim of this study is to investigate the effects of moderate and regular daily
      intake of beer with meals in overweight (body mass index (BMI) of 28-29.9 kg/m2)
      or obese class 1 (BMI of 30-35 kg/m2) individuals without other cardiovascular
      risk factors (dyslipidemia, type 2-diabetes, hypertension) focusing on the
      effects related to changes in weight, in lipoproteins and vascular endothelial
      function. We have performed an open, prospective two-arms longitudinal crossover
      study to investigate the effects associated with regular consumption (four week)
      of alcohol-free-beer (0 g alcohol/day) or traditional-beer (30 g alcohol/day in
      men and 15 g alcohol/day in women) on anthropometrical and biochemical
      parameters, liver and kidney function biomarkers, and vascular endothelial
      function. After four-week intervention with traditional and/or alcohol-free beer,
      BMI did not show any significant change and values for liver and kidney functions
      were within the normal levels. Moderate traditional beer intake did not affect
      lipid levels-however it significantly increased the antioxidant capacity of high
      density lipoprotein (HDL). In addition, apoB-depleted serum (after the four-week
      intervention period) showed a higher potential to promote cholesterol efflux from
      macrophages. Beer consumption did not induce vascular endothelial dysfunction or
      stiffness. In summary, our results based on a 12-week prospective study provide
      evidence that moderate intake of beer (traditional and alcohol-free) does not
      exert vascular detrimental effects nor increases body weight in obese healthy
      individuals. In contrast, moderate intake of beer increases the anti-oxidative
      properties of HDL and facilitates cholesterol efflux, which may prevent lipid
      deposition in the vessel wall.

PMID- 30189621
TI  - Serial MRI Imaging Reveals Minimal Impact of Ketogenic Diet on Established Liver
      Tumor Growth.
AB  - Rodent models of liver tumorigenesis have reproducibly shown that dietary sugar
      intake is a powerful driver of liver tumor initiation and growth. In contrast,
      dietary sugar restriction with ketogenic diets or calorie restriction generally
      prevents liver tumor formation. Ketogenic diet is viewed positively as a
      therapeutic adjuvant; however, most ketogenic diet studies described to date have
      been performed in prevention mode rather than treatment mode. Therefore, it
      remains unclear whether a ketogenic diet can be administered in late stages of
      disease to stall or reverse liver tumor growth. To model the clinically relevant
      treatment mode, we administered a ketogenic diet to mice after liver tumor
      initiation and monitored tumor growth by magnetic resonance imaging (MRI). Male
      C57BL/6 mice were injected with diethylnitrosamine (DEN) at 2 weeks of age and
      fed a chow diet until 39 weeks of age, when they underwent MRI imaging to detect
      liver tumors. Mice were then randomised into two groups and fed either a chow
      diet or switched to a ketogenic diet from 40-48 weeks of age. Serial MRIs were
      performed at 44 and 48 weeks of age. All mice had tumors at study completion and
      there were no differences in total tumor burden between diet groups. Although a
      ketogenic diet has marked protective effects against DEN-induced liver
      tumourigenesis in this mouse model, these data demonstrate that ketogenic diet
      cannot stop the progression of established liver tumors.

PMID- 30189620
TI  - Insonation of Systemically Delivered Cisplatin-Loaded Microbubbles Significantly
      Attenuates Nephrotoxicity of Chemotherapy in Experimental Models of Head and Neck
      Cancer.
AB  - The use of cisplatin (CDDP), the most common chemotherapy drug for head and neck
      cancer, is limited by its undesirable side effects, especially nephrotoxicity. We
      investigated ultrasound microbubbles (USMB) as a tool to increase the local intra
      tumoral CDDP level while decreasing systemic CDDP cytotoxicity. We allowed CDDP
      to interact with human serum albumin and then sonicated the resulting CDDP
      albumin complex to generate CDDP-loaded MBs (CDDP-MBs). We then established a
      head-and-neck tumor-bearing mouse model by implanting FaDu-fLuc/GFP cells into
      severe combined immunodeficiency mice and used IVIS(r) bioluminescence imaging to
      determine the tumor xenograft formation and size. Twice weekly (until Day 33), we
      administered CDDP only, CDDP + MBs + US, CDDP-MBs, or CDDP-MBs + US intravenously
      by tail-vein injection. The US treatment was administered at the tumor site
      immediately after injection. The in vivo systemic distribution of CDDP indicated
      that the kidney was the most vulnerable organ, followed by the liver, and then
      the inner ear. However, CDDP uptake into the kidney and liver was significantly
      decreased in both the CDDP-MBs and CDDP-MBs + US groups, suggesting that MB
      binding significantly reduced the systemic toxicity of CDDP. The CDDP-MBs + US
      treatment reduced the tumor size as effectively as conventional CDDP-only
      chemotherapy. Therefore, the combination of CDDP-MBs with ultrasound is effective
      and significantly attenuates CDDP-associated nephrotoxicity, indicating a
      promising clinical potential for this approach.

PMID- 30189623
TI  - Reducing the Future Risk of Trauma: On the Integration of Global Disaster Policy
      within Specific Health Domains and Established Fields of Practice.
AB  - The global increase in the frequency and severity of natural hazards and extreme
      climatic events necessitates more efficient global and national strategies to
      reduce the likelihood and impact of traumatic consequences for disaster-affected
      populations. The recent inclusion of mental health in the Sendai Framework for
      Disaster Risk Reduction marks a pivotal point in the recognition of the
      significant burden of disasters on mental health, and a global commitment to
      reducing its impacts. Nevertheless, effective agreement implementation and
      efforts to reduce disaster mental health risks are facing significant challenges.
      These include a lack of clarity about the conceptual interlinkages and place of
      disaster risk reduction principles within the field of disaster mental health,
      which is traditionally marked by a prevailing recovery orientation, and the need
      for effective translation into disaster mental health policy and practice.
      Therefore, this study drew on data from interviews with European disaster mental
      health and risk reduction experts in order to appraise the merit and implications
      of a global disaster risk reduction policy for advancing population mental health
      in the context of disaster. Study findings outline existing opportunities,
      challenges, and key strategies for the integration of disaster risk reduction
      within disaster mental health policy and practice.

PMID- 30189622
TI  - Polarization-Controlled and Flexible Single-/Penta-Band Metamaterial Absorber.
AB  - In this paper, a polarization-controlled and flexible metamaterial absorber made
      of a set of wires etched on ultrathin teflon dielectric substrate is proposed.
      The simulation results showed that the proposed absorber achieved single-band
      absorptivity of 99.8% at 6.64 GHz for the TM (transverse magnetic) polarization
      wave and penta-band absorptivity of more than 99% at 11.68 GHz, 13.58 GHz, 15.48
      GHz, 17.38 GHz, and 19.28 GHz for the TE (transverse electric) polarization
      waves. Moreover, each absorption peak had very narrow relative bandwidth and the
      position of penta-band absorption peaks could be adjusted by changing the length
      of the corresponding wire or selecting suitable substrate material according to
      actual requirements, because each wire can independently respond to
      electromagnetic (EM) waves. Furthermore, the surface current distributions
      corresponding to each absorption peak were studied to demonstrate the absorption
      mechanism. The absorption properties of the proposed structure with different
      bending radii and under different incident angles of the EM waves were
      investigated, showing good flexibility and incident angle-insensitive properties.
      In addition, the simulation results were confirmed by measuring a fabricated
      prototype. The proposed absorber may have useful applications in polarizers,
      sensors, bolometers, polarization detectors, etc.

PMID- 30189624
TI  - Oral Bioavailability and Lymphatic Transport of Pueraria Flavone-Loaded Self
      Emulsifying Drug-Delivery Systems Containing Sodium Taurocholate in Rats.
AB  - We developed self-microemulsifying drug-delivery systems (SMEDDS), including bile
      salts, to improve the oral bioavailability of pueraria flavones (PFs). The
      physical properties of the SMEDDS using Cremophor RH 40, and bile salts as mixed
      surfactants at weight ratios of 10:0-0:10 were determined. The particle sizes of
      PFs-SMEDDSNR containing sodium taurocholate (NaTC) and Cremophor RH 40, and PFs
      SMEDDSR containing Cremophor RH 40 were measured upon dilution with deionized
      water and other aqueous media. Dilution volume presented no remarkable effects on
      particle size, whereas dilution media slightly influenced particle size. PFs
      SMEDDSNR and PFs-SMEDDSR provided similar release rates in pH-1.2 hydrochloride
      solution. However, the release rate of PFs-SMEDDSNR was faster than that of PFs
      SMEDDSR in pH-6.8 phosphate buffer containing 20 mM NaTC and 500 U/mL porcine
      pancreas lipase. The pharmacokinetics and bioavailability were measured in rats.
      The oral bioavailability of PFs-SMEDDSNR was 2.57- and 2.28-fold that of a
      suspension of PFs (PFs-suspension) before and after the blockade of the lymphatic
      transport route by cycloheximide, respectively. These results suggested PFs
      SMEDDSNR could significantly improve the oral relative absorption of PFs via the
      lymphatic uptake pathway. SMEDDS containing NaTC may provide an effective
      approach for enhancing the oral bioavailability of PFs.

PMID- 30189625
TI  - Metal Chelating, Inhibitory DNA Damage, and Anti-Inflammatory Activities of
      Phenolics from Rambutan (Nephelium lappaceum) Peel and the Quantifications of
      Geraniin and Corilagin.
AB  - Whereas the preparation and biological properties of rambutan peel phenolics
      (RPP) were explored in our previous studies, the metal chelating, inhibitory DNA
      damage, and anti-inflammatory activities of RPP were evaluated and the important
      phenolics of RPP quantified in this study. Results showed that RPP had high Fe2+
      and Cu2+-chelating activities with EC50 of 0.80 mg/mL and 0.13 mg/mL,
      respectively. RPP effectively decreased the production of hydroxyl radical with
      IC50 of 62.4 MUg/mL. The protective effects of RPP against AAPH-induced DNA
      damage were also explored. RPP efficiently inhibited peroxyl radical-induced
      plasmid DNA strand breakage. The anti-inflammatory effects of RPP were determined
      using a lipopolysaccharide (LPS)-induced RAW 264.7 cell model. RPP significantly
      inhibited the production of nitric oxide (NO) and controlled the levels of
      inducible NO synthase mRNA in LPS-induced RAW 264.7 cells. The inhibitory
      activity increased in a dose-dependent manner. The above bioactivity of RPP was
      associated with its phenolic content and phenolic profiles. Furthermore, the
      contents of geraniin and corilagin in RPP were determined by an ultra-high
      performance liquid chromatography coupled with triple quadruple mass spectrometry
      (UPLC-QQQ-MS), showing 140.02 and 7.87 mg/g extract dry weight. Thus, RPP has
      potential applications as a novel nutraceutical and functional food in health
      promotion.

PMID- 30189626
TI  - Direct Cardiac Reprogramming: A Novel Approach for Heart Regeneration.
AB  - Cardiac diseases are among the most common causes of death globally. Cardiac
      muscle has limited proliferative capacity, and regenerative therapies are highly
      in demand as a new treatment strategy. Although pluripotent reprogramming has
      been developed, it has obstacles, such as a potential risk of tumor formation,
      poor survival of the transplanted cells, and high cost. We previously reported
      that fibroblasts can be directly reprogrammed to cardiomyocytes by overexpressing
      a combination of three cardiac-specific transcription factors (Gata4, Mef2c, Tbx5
      (together, GMT)). We and other groups have promoted cardiac reprogramming by the
      addition of certain miRNAs, cytokines, and epigenetic factors, and unraveled new
      molecular mechanisms of cardiac reprogramming. More recently, we discovered that
      Sendai virus (SeV) vector expressing GMT could efficiently and rapidly reprogram
      fibroblasts into integration-free cardiomyocytes in vitro via robust transgene
      expression. Gene delivery of SeV-GMT also improves cardiac function and reduces
      fibrosis after myocardial infarction in mice. Through direct cardiac
      reprogramming, new cardiomyocytes can be generated and scar tissue reduced to
      restore cardiac function, and, thus, direct cardiac reprogramming may serve as a
      powerful strategy for cardiac regeneration. Here, we provide an overview of the
      previous reports and current challenges in this field.

PMID- 30189628
TI  - Improvement of Ultrasonic Pulse Generator for Automatic Pipeline Inspection.
AB  - This paper presents the improvement of an ultrasonic pulse generator for a
      pipeline inspection gauge (PIG), which uses 64 transducers for inspecting
      distances up to 100 km with an axial resolution fixed at 3 mm and variable speeds
      between 0 and 2 m/s. An ultrasonic pulse generator is composed of a high-voltage
      (HV) MOSFETs, driver logic and an HV power supply. We used a DC-HV DC converter
      device as the HV power supply because it reduces the size of the ultrasound
      system considerably. However, pipeline geometry and inspection effects such as
      hammer and shock cause a variable pulse repetition frequency (PRF), producing
      voltage drops, poor quality of the HV pulse generated, failures in the
      dimensioning of defects and damage to devices by over-voltage. Our improvement is
      to implement a control scheme to maintain the high quality of the HV regardless
      of the variable PRF. To achieve this, we characterized three transfer functions
      of the DC-HV DC converter, varying the connected load to 10%, 45% and 80%. For
      the characterization, we used the least squares technique, considering an
      autoregressive exogenous (ARX) model. Later, we compared three control schemes:
      (1) proportional-integral-derivative (PID) tuned by simultaneous optimization of
      several responses (SOSR), (2) PID tuned by a neural network (NN) and (3) PI tuned
      by the analytical design method (ADM). The metrics used to compare the control
      schemes were the recovery time, the maximum over-voltage and the excess energy
      when the shock and hammer effects happen to occur. Finally, to verify the
      improvement of the HV pulser, we compared the ultrasonic pulses generated for
      various frequencies and amplitudes using the pulse generator with and without the
      control scheme.

PMID- 30189627
TI  - A MALDI-TOF MS Approach for Mammalian, Human, and Formula Milks' Profiling.
AB  - Human milk composition is dynamic, and substitute formulae are intended to mimic
      its protein content. The purpose of this study was to investigate the
      potentiality of matrix-assisted laser desorption/ionization-time-of-flight mass
      spectrometry (MALDI-TOF MS), followed by multivariate data analyses as a tool to
      analyze the peptide profiles of mammalian, human, and formula milks. Breast milk
      samples from women at different lactation stages (2 (n = 5), 30 (n = 6), 60 (n =
      5), and 90 (n = 4) days postpartum), and milk from donkeys (n = 4), cows (n = 4),
      buffaloes (n = 7), goats (n = 4), ewes (n = 5), and camels (n = 2) were
      collected. Different brands (n = 4) of infant formulae were also analyzed.
      Protein content (<30 kDa) was analyzed by MS, and data were exported for
      statistical elaborations. The mass spectra for each milk closely clustered
      together, whereas different milk samples resulted in well-separated mass spectra.
      Human samples formed a cluster in which colostrum constituted a well-defined
      subcluster. None of the milk formulae correlated with animal or human milk,
      although they were specifically characterized and correlated well with each
      other. These findings propose MALDI-TOF MS milk profiling as an analytical tool
      to discriminate, in a blinded way, different milk types. As each formula has a
      distinct specificity, shifting a baby from one to another formula implies a
      specific proteomic exposure. These profiles may assist in milk proteomics for
      easiness of use and minimization of costs, suggesting that the MALDI-TOF MS
      pipelines may be useful for not only milk adulteration assessments but also for
      the characterization of banked milk specimens in pediatric clinical settings.

PMID- 30189629
TI  - Application of PZT Technology and Clustering Algorithm for Debonding Detection of
      Steel-UHPC Composite Slabs.
AB  - A lightweight composite bridge deck system composed of steel orthotropic deck
      stiffened with thin Ultra-High Performance Concrete (UHPC) layer has been
      proposed to eliminate fatigue cracks in orthotropic steel decks. The debonding
      between steel deck and UHPC layer may be introduced during construction and
      operation phases, which could cause adverse consequences, such as crack-induced
      water invasion and distinct reduction of the shear resistance. The piezoelectric
      lead zirconate titanate (PZT)-based technologies are used to detect interfacial
      debonding defects between the steel deck and the UHPC layer. Both impedance
      analysis and wave propagation method are employed to extract debonding features
      of the steel-UHPC composite slab with debonding defect in different sizes and
      thicknesses. Experimental tests are performed on two steel-UHPC composite slabs
      and a conventional steel-concrete composite deck. Additionally, an improved
      Particle Swarm Optimization (PSO)-k-means clustering algorithm is adopted to
      obtain debonding patterns based on the feature data set. The laboratory tests
      demonstrate that the proposed approach provides an effective way to detect
      interfacial debonding of steel-UHPC composite deck.

PMID- 30189631
TI  - Push-Out Bond Strength and SEM Evaluation in Roots Filled with Two Different
      Techniques Using New and Conventional Sealers.
AB  - The aim of this study was to evaluate the influence of calcium-silicate-based
      sealer (Endosequence-BC-Sealer) in roots, filled with thermo-plasticized
      injectable technique aided by Calamus-Flow-Delivery-System, on bond strength to
      radicular dentin, in comparison with conventional epoxy-resin-based sealer (AH
      Plus) along with cold-lateral-compaction technique. Root canals of mandibular
      premolar teeth (n = 80) were instrumented using Protaper Universal rotary files
      and were randomly divided into four experimental groups (n = 20) as follows: (1)
      AH-Plus + cold-lateral-compaction technique; (2) Endosequence-BC-Sealer + cold
      lateral-compaction technique; (3) AH-Plus + thermo-plasticized injectable
      technique; and (4) Endosequence-BC-Sealer + thermo-plasticized injectable
      technique. Horizontal disc shaped samples from each group (n = 60/group) were
      obtained and push-out bond strength testing was performed at a cross-head speed
      of 0.5 mm/min. Data were analyzed statistically using nonparametric Kruskal
      Wallis analysis and Mann-Whitney test (p < 0.001). The statistical analysis
      revealed a significant difference amongst the groups (p < 0.001). The highest
      bond strength values were found in group 1 compared with all the other
      experimental groups (p < 0.001), whereas the lowest bond strength values were
      found in group 4 (p < 0.001). It was concluded that thermo-plasticized injectable
      technique with Calamus-Flow-Delivery-System lowered the bond strengths of the
      sealers, especially Endosequence-BC-Sealer. Therefore, this technique is not
      recommended to calcium-silicate-based sealers. Further studies are needed to
      confirm the findings of this study.

PMID- 30189632
TI  - Microwave Imaging Sensor Using Low Profile Modified Stacked Type Planar Inverted
      F Antenna.
AB  - Microwave imaging is the technique to identify hidden objects from structures
      using electromagnetic waves that can be applied in medical diagnosis. The change
      of dielectric property can be detected using microwave antenna sensor, which can
      lead to localization of abnormality in the human body. This paper presents a
      stacked type modified Planar Inverted F Antenna (PIFA) as microwave imaging
      sensor. Design and performance analysis of the sensor antenna along with
      computational and experimental analysis to identify concealed object has been
      investigated in this study. The dimension of the modified PIFA radiating patch is
      40 * 20 * 10 mm3. The reflector walls used, are 45 mm in length and 0.2-mm-thick
      inexpensive copper sheet is considered for the simulation and fabrication which
      addresses the problems of high expenses in conventional patch antenna. The
      proposed antenna sensor operates at 1.55-1.68 GHz where the maximum realized gain
      is 4.5 dB with consistent unidirectional radiation characteristics. The proposed
      sensor antenna is used to identify tumor in a computational human tissue phantom
      based on reflection and transmission coefficient. Finally, an experiment has been
      performed to verify the antenna's potentiality of detecting abnormality in
      realistic breast phantom.

PMID- 30189630
TI  - Histone Deacetylase Inhibitors and Diabetic Kidney Disease.
AB  - Despite recent clinical trial advances and improvements in clinical care, kidney
      disease due to diabetes remains the most common cause of chronic kidney failure
      worldwide. In the search for new treatments, recent attentions have turned to
      drug repurposing opportunities, including study of the histone deacetylase (HDAC)
      inhibitor class of agents. HDACs are a group of enzymes that remove functional
      acetyl groups from histone and non-histone proteins and they can affect cellular
      function through both epigenetic and non-epigenetic means. Over the past decade,
      several HDAC inhibitors have been adopted into clinical practice, primarily for
      the treatment of hematological malignancy, whereas other existing therapies (for
      instance valproate) have been found to have HDAC inhibitory effects. Here we
      review the current HDAC inhibitors in the clinic and under development; the
      literature evidence supporting the renoprotective effects of HDAC inhibitors in
      experimental diabetic kidney disease; and the adverse effect profiles that may
      prevent existing therapies from entering the clinic for this indication. Whereas
      recent research efforts have shed light on the fundamental actions of HDACs in
      the diabetic kidney, whether these efforts will translate into novel therapies
      for patients will require more specific and better-tolerated therapies.

PMID- 30189633
TI  - Ultra-Wideband (UWB) Antenna Sensor Based Microwave Breast Imaging: A Review.
AB  - Globally, breast cancer is reported as a primary cause of death in women. More
      than 1.8 million new breast cancer cases are diagnosed every year. Because of the
      current limitations on clinical imaging, researchers are motivated to investigate
      complementary tools and alternatives to available techniques for detecting breast
      cancer in earlier stages. This article presents a review of concepts and
      electromagnetic techniques for microwave breast imaging. More specifically, this
      work reviews ultra-wideband (UWB) antenna sensors and their current applications
      in medical imaging, leading to breast imaging. We review the use of UWB sensor
      based microwave energy in various imaging applications for breast tumor related
      diseases, tumor detection, and breast tumor detection. In microwave imaging, the
      back-scattered signals radiating by sensors from a human body are analyzed for
      changes in the electrical properties of tissues. Tumorous cells exhibit higher
      dielectric constants because of their high water content. The goal of this
      article is to provide microwave researchers with in-depth information on
      electromagnetic techniques for microwave imaging sensors and describe recent
      developments in these techniques.

PMID- 30189634
TI  - Franz Diffusion Cell Approach for Pre-Formulation Characterisation of Ketoprofen
      Semi-Solid Dosage Forms.
AB  - This study aimed to evaluate and compare, using the methodology of Franz
      diffusion cells, the ketoprofen (KTP) releasing profiles of two formulations: A
      gel and a conventional suspension. The second aim was to show that this
      methodology might be easily applied for the development of semi-solid prototypes
      and claim proof in pre-formulation stages. Drug release analysis was carried out
      under physiological conditions (pH: 5.6 to 7.4; ionic strength 0.15 M; at 37 
      degrees C) for 24 h. Three independent vertical Franz cells were used with a
      nominal volume of the acceptor compartment of 125 mL and a diffusion area of 2.5
      cm2. Additionally, two different membranes were evaluated: A generic type
      (regenerated cellulose) and a transdermal simulation type (Strat-M(r)). The KTP
      permeation profiles demonstrated that depending on the membrane type and the
      vehicle used, the permeation is strongly affected. High permeation efficiencies
      were obtained for the gel formulation, and the opposite effect was observed for
      the suspension formulation. Moreover, the permeation studies using Strat-M
      membranes represent a reproducible methodology, which is easy to implement for
      pre-formulation stage or performance evaluation of semi-solid pharmaceutical
      products for topical or transdermal administration.

PMID- 30189636
TI  - Transferred PMN-PT Thick Film on Conductive Silver Epoxy.
AB  - Approximately 25 MUm Pb(Mg1/3Nb2/3)O3-PbTiO3 (PMN-PT) thick film was synthesized
      based on a sol-gel/composite route. The obtained PMN-PT thick film was
      successfully transferred from the Silicon substrate to the conductive silver
      epoxy using a novel wet chemical method. The mechanism of this damage free
      transfer was explored and analyzed. Compared with the film on Silicon substrate,
      the transferred one exhibited superior dielectric, ferroelectric and
      piezoelectric properties. These promising results indicate that transferred PMN
      PT thick film possesses the capability for piezoelectric device application,
      especially for ultrasound transducer fabrication. Most importantly, this chemical
      route opens a new path for transfer of thick film.

PMID- 30189635
TI  - Iodide/H2O2 Catalyzed Intramolecular Oxidative Amination for the Synthesis of
      3,2'-Pyrrolidinyl Spirooxindoles.
AB  - An ammonium iodide/hydrogen peroxide-mediated intramolecular oxidative amination
      of 3-aminoalkyl-2-oxindoles was achieved, affording the corresponding 3,2'
      pyrrolidinyl spirooxindoles and their 6- or 7-membered analogous in moderate to
      high yields. This metal-free procedure features very mild reaction conditions,
      non-toxicity and easily handled hydrogen peroxide as a clean oxidant.

PMID- 30189637
TI  - Involvement of Up-Regulation of DR5 Expression and Down-Regulation of c-FLIP in
      Niclosamide-Mediated TRAIL Sensitization in Human Renal Carcinoma Caki Cells.
AB  - Niclosamide is used to treat intestinal parasite infections, as being an
      anthelmintic drug. Recently, several papers suggest the niclosamide inhibits
      multiple signaling pathways, which are highly activated and mutated in cancer.
      Here, niclosamide was evaluated for identifying strategies to overcome tumor
      necrosis factor-related apoptosis-inducing ligand (TRAIL) resistance. Although
      niclosamide (100-200 nM) alone did not bring about cell death, combinations of
      niclosamide and TRAIL led to apoptotic cell death in carcinoma cells, but not in
      normal cells. Niclosamide markedly increased DR5 protein levels, including cell
      surface DR5, and decreased c-FLIP protein levels. Down-regulation of DR5 by
      specific small interfering RNA (siRNA) and ectopic expression of c-FLIP markedly
      blocked niclosamide plus TRAIL-induced apoptosis. Our findings provide that
      niclosamide could overcome resistance to TRAIL through up-regulating DR5 on the
      cell surface and down-regulating c-FLIP in cancer cells. Taken together,
      niclosamide may be an attractive candidate to overcome TRAIL resistance.

PMID- 30189639
TI  - A New Structural Health Monitoring Strategy Based on PZT Sensors and
      Convolutional Neural Network.
AB  - Preliminaries convolutional neural network (CNN) applications have recently
      emerged in structural health monitoring (SHM) systems focusing mostly on
      vibration analysis. However, the SHM literature shows clearly that there is a
      lack of application regarding the combination of PZT-(lead zirconate titanate)
      based method and CNN. Likewise, applications using CNN along with the
      electromechanical impedance (EMI) technique applied to SHM systems are rare. To
      encourage this combination, an innovative SHM solution through the combination of
      the EMI-PZT and CNN is presented here. To accomplish this, the EMI signature is
      split into several parts followed by computing the Euclidean distances among them
      to form a RGB (red, green and blue) frame. As a result, we introduce a dataset
      formed from the EMI-PZT signals of 720 frames, encompassing a total of four types
      of structural conditions for each PZT. In a case study, the CNN-based method was
      experimentally evaluated using three PZTs glued onto an aluminum plate. The
      results reveal an effective pattern classification; yielding a 100% hit rate
      which outperforms other SHM approaches. Furthermore, the method needs only a
      small dataset for training the CNN, providing several advantages for industrial
      applications.

PMID- 30189640
TI  - Ligand-Free Nano-Au Catalysts on Nitrogen-Doped Graphene Filter for Continuous
      Flow Catalysis.
AB  - In this study, the authors rationally designed a high-performance catalytic
      filter for continuous flow catalysis. The catalytic filter consisted of ligand
      free nanoscale gold (nano-Au) catalysts and nitrogen-doped graphene (N-rGO). The
      Au catalyst was fabricated in situ onto a pre-formed N-rGO support by the NaBH4
      reduction of the Au precursor, and the size of the nano-Au was fine-tuned. A
      hydrothermal pretreatment of graphene oxide enriched nitrogen-containing species
      on the surface of two-dimensional graphene supports and enhanced the affinity of
      Au precursors onto the support via electrocatalytic attraction. The nano-Au
      catalysts acted as high-performance catalysts, and the N-rGO acted as ideal
      filter materials to anchor the catalysts. The catalytic activity of the as
      designed catalytic filter was evaluated using 4-nitrophenol (4-NP) hydrogenation
      as a model catalytic reaction. The catalytic filters demonstrated superior
      catalytic activity and excellent stability, where a complete 4-nitrophenol
      conversion was readily achieved via a single pass through the catalytic filter.
      The as-fabricated catalytic filter outperformed the conventional batch reactors
      due to evidently improved mass transport. Some key operational parameters
      impacting the catalytic performance were identified and optimized. A similar
      catalytic performance was also observed for three 4-nitrophenol spiked real water
      samples (e.g., surface water, tap water, and industrial dyeing wastewater). The
      excellent catalytic activity of the nano-Au catalysts combined with the two
      dimensional and mechanically stable graphene allowed for the rational design of
      various continuous flow catalytic membranes for potential industrial
      applications.

PMID- 30189638
TI  - Transcriptomic and Proteomic Analyses Reveal the Diversity of Venom Components
      from the Vaejovid Scorpion Serradigitus gertschi.
AB  - To understand the diversity of scorpion venom, RNA from venomous glands from a
      sawfinger scorpion, Serradigitus gertschi, of the family Vaejovidae, was
      extracted and used for transcriptomic analysis. A total of 84,835 transcripts
      were assembled after Illumina sequencing. From those, 119 transcripts were
      annotated and found to putatively code for peptides or proteins that share
      sequence similarities with the previously reported venom components of other
      species. In accordance with sequence similarity, the transcripts were classified
      as potentially coding for 37 ion channel toxins; 17 host defense peptides; 28
      enzymes, including phospholipases, hyaluronidases, metalloproteases, and serine
      proteases; nine protease inhibitor-like peptides; 10 peptides of the cysteine
      rich secretory proteins, antigen 5, and pathogenesis-related 1 protein
      superfamily; seven La1-like peptides; and 11 sequences classified as "other venom
      components". A mass fingerprint performed by mass spectrometry identified 204
      components with molecular masses varying from 444.26 Da to 12,432.80 Da, plus
      several higher molecular weight proteins whose precise masses were not
      determined. The LC-MS/MS analysis of a tryptic digestion of the soluble venom
      resulted in the de novo determination of 16,840 peptide sequences, 24 of which
      matched sequences predicted from the translated transcriptome. The database
      presented here increases our general knowledge of the biodiversity of venom
      components from neglected non-buthid scorpions.

PMID- 30189641
TI  - Transcriptome Analysis of Novosphingobium pentaromativorans US6-1 Reveals the Rsh
      Regulon and Potential Molecular Mechanisms of N-acyl-l-homoserine Lactone
      Accumulation.
AB  - In most bacteria, a bifunctional Rsh responsible for (p)ppGpp metabolism is the
      key player in stringent response. To date, no transcriptome-wide study has been
      conducted to investigate the Rsh regulon, and the molecular mechanism of how Rsh
      affects the accumulation of N-acyl-l-homoserine lactone (AHL) remains unknown in
      sphingomonads. In this study, we identified an rshUS6-1 gene by sequence analysis
      in Novosphingobium pentaromativorans US6-1, a member of the sphingomonads. RNA
      seq was used to determine transcription profiles of the wild type and the ppGpp
      deficient rshUS6-1 deletion mutant (?rsh). There were 1540 genes in the RshUS6-1
      regulon, including those involved in common traits of sphingomonads such as
      exopolysaccharide biosynthesis. Furthermore, both RNA-seq and quantitative real
      time polymerase chain reaction (qRT-PCR) showed essential genes for AHL
      production (novI and novR) were positively regulated by RshUS6-1 during the
      exponential growth phase. A degradation experiment indicated the reason for the
      AHL absence in ?rsh was unrelated to the AHL degradation. According to RNA-seq,
      we proposed sigmaE, DksA, Lon protease and RNA degradation enzymes might be
      involved in the RshUS6-1-dependent expression of novI and novR. Here, we report
      the first transcriptome-wide analysis of the Rsh regulon in sphingomonads and
      investigate the potential mechanisms regulating AHL accumulation, which is an
      important step towards understanding the regulatory system of stringent response
      in sphingomonads.

PMID- 30189642
TI  - Grape Seed Proanthocyanidins Improve White Adipose Tissue Expansion during Diet
      Induced Obesity Development in Rats.
AB  - The development of metabolic complications associated with obesity has been
      correlated with a failure of white adipose tissue (WAT) to expand. Our group has
      previously reported that a 12-week administration of grape seed proanthocyanidin
      extract (GSPE) together with an obesogenic diet mitigated the development of
      cardiometabolic complications in rats. Using the same cohort of animals, we aim
      to elucidate whether the prevention of cardiometabolic complications by
      proanthocyanidins is produced by a healthier expansion of visceral WAT and/or an
      induction of the browning of WAT. For this, adipocyte size and number in
      retroperitoneal WAT (rWAT) were determined by histological analyses, and the gene
      expression levels of markers of adipogenesis, browning, and WAT functionality
      were quantified by RT-qPCR. The long-term administration of GSPE together with an
      obesogenic diet expanded rWAT via an increase in the adipocyte number and a
      preventive decrease in the adipocyte size in a dose-dependent manner. At the
      molecular level, GSPE seems to induce WAT adipogenesis through the upregulation
      of peroxisome proliferator-activated receptor (Ppargamma) in a Sirtuin 1 (Sirt1)
      dependent manner. In conclusion, the healthier visceral WAT expansion induced by
      proanthocyanidins supplementation may explain the improvement in the
      cardiometabolic risks associated with obesogenic diets.

PMID- 30189643
TI  - Cell-Based Reporter Release Assay to Determine the Potency of Proteolytic
      Bacterial Neurotoxins.
AB  - Despite the implementation of cell-based replacement methods, the mouse lethality
      assay is still frequently used to determine the activity of botulinum toxin
      (BoNT) for medical use. One explanation is that due to the use of neoepitope
      specific antibodies to detect the cleaved BoNT substrate, the currently devised
      assays can detect only one specific serotype of the toxin. Recently, we developed
      a cell-based functional assay, in which BoNT activity is determined by inhibiting
      the release of a reporter enzyme that is liberated concomitantly with the
      neurotransmitter from neurosecretory vesicles. In theory, this assay should be
      suitable to detect the activity of any BoNT serotype. Consistent with this
      assumption, the current study shows that the stimulus-dependent release of a
      luciferase from a differentiated human neuroblastoma-based reporter cell line
      (SIMA-hPOMC1-26-GLuc cells) was inhibited by BoNT-A and-C. Furthermore, this was
      also inhibited by BoNT-B and tetanus toxin to a lesser extent and at higher
      concentrations. In order to provide support for the suitability of this technique
      in practical applications, a dose-response curve obtained with a pharmaceutical
      preparation of BoNT-A closely mirrored the activity determined in the mouse
      lethality assay. In summary, the newly established cell-based assay may represent
      a versatile and specific alternative to the mouse lethality assay and other
      currently established cell-based assays.

PMID- 30189644
TI  - Molecular Recognition of Parallel G-quadruplex [d-(TTGGGGT)]4 Containing
      Tetrahymena Telomeric DNA Sequence by Anticancer Drug Daunomycin: NMR-Based
      Structure and Thermal Stability.
AB  - The anticancer drug daunomycin exerts its influence by multiple strategies of
      action to interfere with gene functioning. Besides inhibiting DNA/RNA synthesis
      and topoisomerase-II, it affects the functional pathway of telomere maintenance
      by the telomerase enzyme. We present evidence of the binding of daunomycin to
      parallel-stranded tetramolecular [d-(TTGGGGT)]4 guanine (G)-quadruplex DNA
      comprising telomeric DNA from Tetrahymena thermophilia by surface plasmon
      resonance and Diffusion Ordered SpectroscopY (DOSY). Circular Dichroism (CD)
      spectra show the disruption of daunomycin dimers, suggesting the end-stacking and
      groove-binding of the daunomycin monomer. Proton and phosphorus-31 Nuclear
      Magnetic Resonance (NMR) spectroscopy show a sequence-specific interaction and a
      clear proof of absence of intercalation of the daunomycin chromophore between
      base quartets or stacking between G-quadruplexes. Restrained molecular dynamics
      simulations using observed short interproton distance contacts depict interaction
      at the molecular level. The interactions involving ring A and daunosamine
      protons, the stacking of an aromatic ring of daunomycin with a terminal G6
      quartet by displacing the T7 base, and external groove-binding close to the T1-T2
      bases lead to the thermal stabilization of 15  degrees C, which is likely to
      inhibit the association of telomerase with telomeres. The findings have
      implications in the structure-based designing of anthracycline drugs as potent
      telomerase inhibitors.

PMID- 30189645
TI  - Co-Amorphous Screening for the Solubility Enhancement of Poorly Water-Soluble
      Mirabegron and Investigation of Their Intermolecular Interactions and Dissolution
      Behaviors.
AB  - In the present study, the screening of Mirabegron (MBR) co-amorphous was
      performed to produce water-soluble and thermodynamically stable MBR co-amorphous
      with the purpose of overcoming the water solubility problem of MBR. MBR is
      Biopharmaceutics Classification System (BCS) class II drug used for the treatment
      of an overreactive bladder. The co-amorphous screening was carried out by means
      of the vacuum evaporation crystallization technique in methanol solvent using
      three water-soluble carboxylic acids, characterized by a pKa difference greater
      than 3 with MBR such as fumaric acid (FA), l-pyroglutamic acid (PG), and citric
      acid (CA). Powder X-ray diffraction (PXRD) results suggested that all solid
      materials produced at MBR-FA (1 equivalent (eq.)/1 equivalent (eq.)), MBR-PG (1
      eq./1 eq.), and MBR-CA (1 eq./1 eq.) conditions were amorphous state solid
      materials. Furthermore, by means of solution-state nuclear magnetic resonance
      (NMR) (1H, 13C, and 2D) and attenuated total reflection Fourier transform
      infrared (ATR-FTIR) spectroscopy, we could assess that MBR and carboxylic acid
      molecules were linked via ionic interactions to produce MBR co-amorphous.
      Besides, solid-state cross polarization (CP)/magic angle spinning (MAS) 13C-NMR
      analysis was conducted for additional assessment of MBR co-amorphous. Afterwards,
      dissolution tests of MBR co-amorphouses, MBR crystalline solid, and MBR amorphous
      were carried out for 12 h to evaluate and to compare their solubilities,
      dissolution rates, and phase transformation phenomenon. Here, the results
      suggested that MBR co-amorphouses displayed more than 57-fold higher aqueous
      solubility compared to MBR crystalline solid, and PXRD monitoring result
      suggested that MBR co-amorphouses were able to maintain their amorphous state for
      more than 12 h. The same results revealed that MBR amorphous exhibited increased
      solubility of approximatively 6.7-fold higher compared to MBR crystalline solid.
      However, the PXRD monitoring result suggested that MBR amorphous undergo rapid
      phase transformation to crystalline form in just 35 min and that within an hour
      all MBR amorphous are completely converted to crystalline solid. Accordingly, the
      increase in MBR co-amorphous' solubility was attributed to the presence of ionic
      interactions in MBR co-amorphous molecules. Moreover, from the differential
      scanning calorimetry (DSC) monitoring results, we predicted that the high glass
      transition temperature (Tg) of MBR co-amorphous compared to MBR amorphous was the
      main factor influencing the phase stability of MBR co-amorphous.

PMID- 30189646
TI  - Performance Characterization of GNSS/IMU/DVL Integration under Real Maritime
      Jamming Conditions.
AB  - Currently Global Navigation Satellite Systems (GNSSs) are the primary source for
      the determination of absolute position, navigation, and time (PNT) for merchant
      vessel navigation. Nevertheless, the performance of GNSSs can strongly degrade
      due to space weather events, jamming, and spoofing. Especially the increasing
      availability and adoption of low cost jammers lead to the question of how a
      continuous provision of PNT data can be realized in the vicinity of these
      devices. In general, three possible solutions for that challenge can be seen: (i)
      a jamming-resistant GNSS receiver; (ii) the usage of a terrestrial backup system;
      or (iii) the integration of GNSS with other onboard navigation sensors such as a
      speed log, a gyrocompass, and inertial sensors (inertial measurement unit-IMU).
      The present paper focuses on the third option by augmenting a classical IMU/GNSS
      sensor fusion scheme with a Doppler velocity log. Although the benefits of
      integrated IMU/GNSS navigation system have been already demonstrated for marine
      applications, a performance evaluation of such a multi-sensor system under real
      jamming conditions on a vessel seems to be still missing. The paper evaluates
      both loosely and tightly coupled fusion strategies implemented using an unscented
      Kalman filter (UKF). The performance of the proposed scheme is evaluated using
      the civilian maritime jamming testbed in the Baltic Sea.

PMID- 30189648
TI  - An Autonomous Vehicle Navigation System Based on Inertial and Visual Sensors.
AB  - The strapdown inertial navigation system (SINS) is widely used in autonomous
      vehicles. However, the random drift error of gyroscope leads to serious
      accumulated navigation errors during long continuous operation of SINS alone. In
      this paper, we propose to combine the Inertial Measurement Unit (IMU) data with
      the line feature parameters from a camera to improve the navigation accuracy. The
      proposed method can also maintain the autonomy of the navigation system.
      Experimental results show that the proposed inertial-visual navigation system can
      mitigate the SINS drift and improve the accuracy, stability, and reliability of
      the navigation system.

PMID- 30189647
TI  - Profiles of Physical Fitness Risk Behaviours in School Adolescents from the ASSO
      Project: A Latent Class Analysis.
AB  - The aim of the present investigation was to describe profiles of adolescents'
      fitness level, identify latent classes of fitness-related risk behaviours, and
      describe their sociodemographic and environmental predictors. In total, 883
      adolescents (16.4 +/- 1.4 years; 167.3 +/- 10.4 cm; 62.8 +/- 13.5 kg; 62.2%
      males) were assessed for personal and lifestyle information and for physical
      fitness components. Eleven possible fitness determinants and seven predictors
      were included. Latent class analysis (LCA) was used to determine fitness-related
      risk behaviours. Logistic regressions predicted class membership and assessed
      associations with fitness levels and fitness components. Five latent classes were
      recognised: 1-virtuous, 30.7% of respondents; 2-low physical activity/sport,
      18.8%; 3-incorrect alcohol/food habits, 25.8%; 4-health risk/overweight, 15.9%; 5
      malaise/diseases, 8.8%. Sex, age, parents' overweightness/obesity and education,
      and school type predicted most classes significantly. Compared to class 1, class
      2 had higher odds of having all poor fitness components except upper body maximal
      strength; class 4 had higher risk of low muscular endurance; and class 5 was
      likely to have lower maximal strength, muscular endurance, and speed/agility.
      Educating adolescents to reach a sufficient practice of PA/sport could help
      decreasing the risk of low health-related fitness more than discouraging them
      from using alcohol, addressing proper food behaviours and habits, and helping
      them understand their psychophysical malaise symptoms.

PMID- 30189650
TI  - Hygrothermal and Acoustical Performance of Starch-Beet Pulp Composites for
      Building Thermal Insulation.
AB  - This article deals with the elaboration and the characterization of an innovative
      100% plant-based green composite made solely of beet pulp (BP) and potato starch
      (S). Using this type of material in insulation applications seems a good solution
      to reduce the CO2 gas emissions in building. The influence of the starch amount
      on composite characteristics was studied. Four mixtures were considered with
      different S/BP mass ratios (0.1, 0.2, 0.3 and 0.4). The physical properties of
      these materials were studied in terms of porosity, apparent and absolute
      densities, thermal conductivity, and hygric properties. The influence of humidity
      content on acoustical properties was studied as a function of frequency. Test
      results show a real impact of both starch and humidity contents on the
      hygrothermal and acoustical properties of the studied material due to the
      porosity. The composite with the lowest amount of starch (S/BP = 0.1) seems to be
      the optimal composition in terms of the hygrothermal and acoustical behaviors.

PMID- 30189651
TI  - Motion Artifact Correction of Multi-Measured Functional Near-Infrared
      Spectroscopy Signals Based on Signal Reconstruction Using an Artificial Neural
      Network.
AB  - In this paper, a new motion artifact correction method is proposed based on multi
      channel functional near-infrared spectroscopy (fNIRS) signals. Recently, wavelet
      transform and hemodynamic response function-based algorithms were proposed as
      methods of denoising and detrending fNIRS signals. However, these techniques
      cannot achieve impressive performance in the experimental environment with lots
      of movement such as gait and rehabilitation tasks because hemodynamic responses
      have features similar to those of motion artifacts. Moreover, it is difficult to
      correct motion artifacts in multi-measured fNIRS systems, which have multiple
      channels and different noise features in each channel. Thus, a new motion
      artifact correction method for multi-measured fNIRS is proposed in this study,
      which includes a decision algorithm to determine the most contaminated fNIRS
      channel based on entropy and a reconstruction algorithm to correct motion
      artifacts by using a wavelet-decomposed back-propagation neural network. The
      experimental data was achieved from six subjects and the results were analyzed in
      comparing conventional algorithms such as HRF smoothing, wavelet denoising, and
      wavelet MDL. The performance of the proposed method was proven experimentally
      using the graphical results of the corrected fNIRS signal, CNR that is a
      performance evaluation index, and the brain activation map.

PMID- 30189649
TI  - Pregnancy Related Health Care Needs in Refugees-A Current Three Center Experience
      in Europe.
AB  - Background: Immigration into Europe has reached an all-time high. Provision of
      coordinated healthcare, especially to refugee women that are at increased risk
      for adverse pregnancy outcomes, is a challenge for receiving health care systems.
      Methods: We assessed pregnancy rates and associated primary healthcare needs in
      three refugee cohorts in Northern Germany during the current crisis. Results: Out
      of n = 2911 refugees, 18.0% were women of reproductive age, and 9.1% of these
      were pregnant. Pregnancy was associated with a significant, 3.7-fold increase in
      primary health care utilization. Language barrier and cultural customs impeded
      healthcare to some refugee pregnant women. The most common complaints were demand
      for pregnancy checkup without specific symptoms (48.6%), followed by abdominal
      pain or urinary tract infections (in 11.4% of cases each). In 4.2% of
      pregnancies, severe complications such as syphilis or suicide attempts occurred.
      Discussion: We present data on pregnancy rates and pregnancy associated medical
      need in three current refugee cohorts upon arrival in Germany. Healthcare
      providers should be particularly aware of the requirements of pregnant migrants
      and should adapt primary caretaking strategies accordingly.

PMID- 30189652
TI  - The Thomsen-Friedenreich Antigen: A Highly Sensitive and Specific Predictor of
      Microsatellite Instability in Gastric Cancer.
AB  - Microsatellite instability (MSI) is a distinct molecular subtype of gastric
      cancer. In recent years, the clinical consequences of MSI and the therapeutic
      opportunities to target this peculiar cancer subtype became evident. However,
      despite the importance of MSI for the stratification of patients, the time and
      resources required for diagnosis still present an obstacle. In an attempt to
      identify a new marker for MSI in gastric cancer, we evaluated the expression of
      five cancer-associated glycan epitopes in a cohort of 13 MSI and 17
      microsatellite stable (MSS) cases. Our analysis revealed a highly significant (p
      < 0.001) association between the expression of the Thomsen-Friedenreich (TF)
      antigen and MSI status. Hence, we present here the identification of the first
      single marker for MSI in gastric cancer, excelling with a specificity of 94%
      (16/17), sensitivity of 69.2% (9/13), negative predictive value of 80% (16/20),
      and positive predictive value of 90% (9/10). The TF antigen, detected by simple
      antibody-based assays, is highly specific for carcinoma being undetectable in
      gastric healthy and premalignant epithelia. This finding lays the basis for new
      studies and holds promise in improving the rapid identification of MSI in the
      clinical setting.

PMID- 30189654
TI  - Palm Kernel Shell Activated Carbon as an Inorganic Framework for Shape-Stabilized
      Phase Change Material.
AB  - The preparation of activated carbon using palm kernel shells as the precursor
      (PKSAC) was successfully accomplished after the parametric optimization of the
      carbonization temperature, carbonization holding time, and the ratio of the
      activator (H3PO4) to the precursor. Optimization at 500  degrees C for 2 h of
      carbonization with 20% H3PO4 resulted in the highest surface area of the
      activated carbon (C20) of 1169 m2 g-1 and, with an average pore size of 27 A.
      Subsequently, the preparation of shape-stabilized phase change material (SSPCM
      C20) was done by the encapsulation of n-octadecane into the pores of the PKSAC,
      C20. The field emission scanning electron microscope images and the nitrogen gas
      adsorption-desorption isotherms show that n-octadecane was successfully
      encapsulated into the pores of C20. The resulting SSPCM-C20 nano-composite shows
      good thermal reliability which is chemically and thermally stable and can stand
      up to 500 melting and freezing cycles. This research work provided a new strategy
      for the preparation of SSPCM material for thermal energy storage application
      generated from oil palm waste.

PMID- 30189653
TI  - Demographic and Psychological Factors Associated with Feelings of Antibiotic
      Entitlement in New Zealand.
AB  - Patients' expectations of being prescribed antibiotics can have an important
      influence on inappropriate prescribing. Therefore, it is important to understand
      the drivers of patients' antibiotic expectations. The 2015/16 New Zealand
      Attitudes and Values Study measured sense of entitlement to antibiotics in a
      nationally representative sample of New Zealanders (n = 13,484). Participants
      were asked to rate their agreement with the statement "If I go to my doctor/GP
      with a minor illness (e.g., sore throat, cough, runny nose, etc.), I think that I
      should be prescribed antibiotics by default." Eighty percent of participants
      showed low feelings of antibiotic entitlement, while 18.5% exhibited moderate and
      3.7% high feelings of entitlement. People of ethnic minority, lower socio
      economic status, and with diabetes expressed higher expectations of being
      prescribed antibiotics. This may be partially based on a higher risk of rheumatic
      fever or other complications. Men, religious people, those with lower educational
      attainment and self-rated health, but greater psychological distress and feelings
      of control over their health exhibited higher feelings of antibiotic entitlement.
      Those high on Extraversion, Conscientiousness, and Narcissism, but low on
      Agreeableness and Openness, also showed greater feelings of entitlement. Our
      findings help identify key characteristics of those more likely to express
      inappropriate expectations of antibiotic prescription.

PMID- 30189655
TI  - Spectral Analysis and Parameter Identification of Textile-Based Dye-Sensitized
      Solar Cells.
AB  - Linearized equivalent electrical-circuit representation of dye-sensitized solar
      cells is helpful both for the better understanding of the physical processes in
      the cell as well as for various optimizations of the cells. White-box and grey
      box modelling approaches are well-known and they are widely used for standard
      cell types. However, in the case of new cell types or the lack of deep knowledge
      of the cell's physic such approaches may not be applicable immediately. In this
      article a black-box approach for such cases is presented applied together with
      spectral analysis. The spectral analysis and the black-box approach were as first
      validated with a standard glass-based dye-sensitized solar cell and thereafter
      applied for the characterization of a new type of textile-based dye-sensitized
      solar cells. Although there are still improvement potentials, the results are
      encouraging and the authors believe that the black-box method with spectral
      analysis may be used particularly for new types of dye-sensitized solar cells.

PMID- 30189656
TI  - Global Long Noncoding RNA and mRNA Expression Changes between Prenatal and
      Neonatal Lung Tissue in Pigs.
AB  - Lung tissue plays an important role in the respiratory system of mammals after
      birth. Early lung development includes six key stages, of which the saccular
      stage spans the pre- and neonatal periods and prepares the distal lung for
      alveolarization and gas-exchange. However, little is known about the changes in
      gene expression between fetal and neonatal lungs. In this study, we performed
      transcriptomic analysis of messenger RNA (mRNA) and long noncoding RNA (lncRNA)
      expressed in the lung tissue of fetal and neonatal piglets. A total of 19,310
      lncRNAs and 14,579 mRNAs were identified and substantially expressed.
      Furthermore, 3248 mRNAs were significantly (FDR-adjusted p value <= 0.05, FDR:
      False Discovery Rate) differentially expressed and were mainly enriched in
      categories related to cell proliferation, immune response, hypoxia response, and
      mitochondrial activation. For example, CCNA2, an important gene involved in the
      cell cycle and DNA replication, was upregulated in neonatal lungs. We also
      identified 452 significantly (FDR-adjusted p value <= 0.05) differentially
      expressed lncRNAs, which might function in cell proliferation, mitochondrial
      activation, and immune response, similar to the differentially expressed mRNAs.
      These results suggest that differentially expressed mRNAs and lncRNAs might co
      regulate lung development in early postnatal pigs. Notably, the TU64359 lncRNA
      might promote distal lung development by up-regulating the heparin-binding
      epidermal growth factor-like (HB-EGF) expression. Our research provides basic
      lung development datasets and will accelerate clinical researches of newborn lung
      diseases with pig models.

PMID- 30189658
TI  - Automatic Calibration of an Around View Monitor System Exploiting Lane Markings.
AB  - This paper proposes a method that automatically calibrates four cameras of an
      around view monitor (AVM) system in a natural driving situation. The proposed
      method estimates orientation angles of four cameras composing the AVM system, and
      assumes that their locations and intrinsic parameters are known in advance. This
      method utilizes lane markings because they exist in almost all on-road situations
      and appear across images of adjacent cameras. It starts by detecting lane
      markings from images captured by four cameras of the AVM system in a cost
      effective manner. False lane markings are rejected by analyzing the statistical
      properties of the detected lane markings. Once the correct lane markings are
      sufficiently gathered, this method first calibrates the front and rear cameras,
      and then calibrates the left and right cameras with the help of the calibration
      results of the front and rear cameras. This two-step approach is essential
      because side cameras cannot be fully calibrated by themselves, due to
      insufficient lane marking information. After this initial calibration, this
      method collects corresponding lane markings appearing across images of adjacent
      cameras and simultaneously refines the initial calibration results of four
      cameras to obtain seamless AVM images. In the case of a long image sequence, this
      method conducts the camera calibration multiple times, and then selects the
      medoid as the final result to reduce computational resources and dependency on a
      specific place. In the experiment, the proposed method was quantitatively and
      qualitatively evaluated in various real driving situations and showed promising
      results.

PMID- 30189657
TI  - Genome-Wide Identification, Classification and Expression Analysis of the HSP
      Gene Superfamily in Tea Plant (Camellia sinensis).
AB  - Heat shock proteins (HSPs) function as molecular chaperones. These proteins are
      encoded by a multigene family whose members play crucial roles in plant growth,
      development and stress response. However, little is known about the HSP gene
      superfamily in tea plant. In this study, a total of 47 CsHSP genes were
      identified, including 7 CsHSP90, 18 CsHSP70, and 22 CssHSP genes. Phylogenetic
      and composition analyses showed that CsHSP proteins in the same subfamily have
      similar gene structures and conserved motifs, but significant differences exist
      in the different subfamilies. In addition, expression analysis revealed that
      almost all CsHSP genes were specifically expressed in one or more tissues, and
      significantly induced under heat and drought stress, implying that CsHSP genes
      play important roles in tea plant growth, development, and response to heat and
      drought stress. Furthermore, a potential interaction network dominated by CsHSPs,
      including HSP70/HSP90 organizing protein (HOP) and heat shock transcription
      factor (HSF), is closely related to the abovementioned processes. These results
      increase our understanding of CsHSP genes and their roles in tea plant, and thus,
      this study could contribute to the cloning and functional analysis of CsHSP genes
      and their encoded proteins in the future.

PMID- 30189659
TI  - Serum and Hepatic Autofluorescence as a Real-Time Diagnostic Tool for Early
      Cholestasis Assessment.
AB  - While it is well established that various factors can impair the production and
      flow of bile and lead to cholestatic disease in hepatic and extrahepatic sites,
      an enhanced assessment of the biomarkers of the underlying pathophysiological
      mechanisms is still needed to improve early diagnosis and therapeutic strategies.
      Hence, we investigated fluorescing endogenous biomolecules as possible intrinsic
      biomarkers of molecular and cellular changes in cholestasis. Spectroscopic
      autofluorescence (AF) analysis was performed using a fiber optic probe (366 nm
      excitation), under living conditions and in serum, on the livers of male Wistar
      rats submitted to bile duct ligation (BDL, 24, 48, and 72 h). Biomarkers of liver
      injury were assayed biochemically. In the serum, AF analysis distinctly detected
      increased bilirubin at 24 h BDL. A continuous, significant increase in red
      fluorescing porphyrin derivatives indicated the subversion of heme metabolism,
      consistent with an almost twofold increase in the serum iron at 72 h BDL. In the
      liver, changes in the AF of NAD(P)H and flavins, as well as lipopigments,
      indicated the impairment of mitochondrial functionality, oxidative stress, and
      the accumulation of oxidative products. A serum/hepatic AF profile can be thus
      proposed as a supportive diagnostic tool for the in situ, real-time study of bio
      metabolic alterations in bile duct ligation (BDL) in experimental hepatology,
      with the potential to eventually translate to clinical diagnosis.

PMID- 30189662
TI  - ZnO/ZnAl2O4 Nanocomposite with 3D Sphere-Like Hierarchical Structure for
      Photocatalytic Reduction of Aqueous Cr(VI).
AB  - Three dimensional (3D) ZnO/ZnAl2O4 nanocomposites (ZnnAl-MMO) were synthesized by
      a simple urea-assisted hydrothermal process and subsequent high-temperature
      calcination. The as-prepared samples and their precursors were characterized by X
      ray diffraction (XRD), Scanning electron microscopy (SEM), Transmission electron
      microscopy (TEM), UV-Vis diffuse reflectance spectroscopy (DRS), and
      Photoluminescence spectra (PL). It was observed that the morphology of ZnnAl-MMO
      nanocomposites could be tuned from cubic aggregates, hierarchically flower-like
      spheres to porous microspheres by simply changing the molar ratio of metal
      cations of the starting reaction mixtures. The photocatalytic performance of
      ZnO/ZnAl2O4 nanocomposites in the photoreduction of aqueous Cr(VI) indicated that
      the as-prepared 3D hierarchical sphere-like ZnnAl-MMO nanocomposite showed
      excellent photocatalytic activity of Cr(VI) reduction under UV light irradiation.
      The results indicated that the maximum removal percentage of aqueous Cr(VI) was
      98% within four hours at 10 mg/L initial concentration of Cr(VI), owing to the
      effective charge separation and diversion of photogenerated carriers across the
      heterojunction interface of the composite. Our study put forward a facile method
      to fabricate hierarchical ZnO/ZnAl2O4 composites with potential applications for
      wastewater treatment.

PMID- 30189661
TI  - Oligonucleotides Targeting Telomeres and Telomerase in Cancer.
AB  - Telomeres and telomerase have become attractive targets for the development of
      anticancer therapeutics due to their involvement in cancer cell immortality.
      Currently, several therapeutics have been developed that directly target
      telomerase and telomeres, such as telomerase inhibitors and G-quadruplex
      stabilizing ligands. Telomere-specific oligonucleotides that reduce telomerase
      activity and disrupt telomere architecture are also in development as novel
      anticancer therapeutics. Specifically, GRN163L and T-oligos have demonstrated
      promising anticancer activity in multiple cancers types via induction of potent
      DNA damage responses. Currently, several miRNAs have been implicated in the
      regulation of telomerase activity and may prove to be valuable targets in the
      development of novel therapies by reducing expression of telomerase subunits.
      Targeting miRNAs that are known to increase expression of telomerase subunits may
      be another strategy to reduce carcinogenesis. This review aims to provide a
      comprehensive understanding of current oligonucleotide-based anticancer therapies
      that target telomeres and telomerase. These studies may help design novel
      therapeutic approaches to overcome the challenges of oligonucleotide therapy in a
      clinical setting.

PMID- 30189663
TI  - Development of a Biosensory Computer Application to Assess Physiological and
      Emotional Responses from Sensory Panelists.
AB  - In sensory evaluation, there have been many attempts to obtain responses from the
      autonomic nervous system (ANS) by analyzing heart rate, body temperature, and
      facial expressions. However, the methods involved tend to be intrusive, which
      interfere with the consumers' responses as they are more aware of the
      measurements. Furthermore, the existing methods to measure different ANS
      responses are not synchronized among them as they are measured independently.
      This paper discusses the development of an integrated camera system paired with
      an Android PC application to assess sensory evaluation and biometric responses
      simultaneously in the Cloud, such as heart rate, blood pressure, facial
      expressions, and skin-temperature changes using video and thermal images acquired
      by the integrated system and analyzed through computer vision algorithms written
      in Matlab(r), and FaceReaderTM. All results can be analyzed through customized
      codes for multivariate data analysis, based on principal component analysis and
      cluster analysis. Data collected can be also used for machine-learning modeling
      based on biometrics as inputs and self-reported data as targets. Based on
      previous studies using this integrated camera and analysis system, it has shown
      to be a reliable, accurate, and convenient technique to complement the
      traditional sensory analysis of both food and nonfood products to obtain more
      information from consumers and/or trained panelists.

PMID- 30189660
TI  - Exercise-Induced Oxidative Stress and the Effects of Antioxidant Intake from a
      Physiological Viewpoint.
AB  - It is well established that the increase in reactive oxygen species (ROS) and
      free radicals production during exercise has both positive and negative
      physiological effects. Among them, the present review focuses on oxidative stress
      caused by acute exercise, mainly on evidence in healthy individuals. This review
      also summarizes findings on the determinants of exercise-induced oxidative stress
      and sources of free radical production. Moreover, we outline the effects of
      antioxidant supplementation on exercise-induced oxidative stress, which have been
      studied extensively. Finally, the following review briefly summarizes future
      tasks in the field of redox biology of exercise. In principle, this review covers
      findings for the whole body, and describes human trials and animal experiments
      separately.

PMID- 30189664
TI  - Improved Chondrogenic Differentiation of rAAV SOX9-Modified Human MSCs Seeded in
      Fibrin-Polyurethane Scaffolds in a Hydrodynamic Environment.
AB  - The repair of focal articular cartilage defects remains a problem. Combining gene
      therapy with tissue engineering approaches using bone marrow-derived mesenchymal
      stem cells (MSCs) may allow the development of improved options for cartilage
      repair. Here, we examined whether a three-dimensional fibrin-polyurethane
      scaffold provides a favorable environment for the effective chondrogenic
      differentiation of human MSCs (hMSCs) overexpressing the cartilage-specific SOX9
      transcription factor via recombinant adeno-associated virus (rAAV) -mediated gene
      transfer cultured in a hydrodynamic environment in vitro. Sustained SOX9
      expression was noted in the constructs for at least 21 days, the longest time
      point evaluated. Such spatially defined SOX9 overexpression enhanced
      proliferative, metabolic, and chondrogenic activities compared with control
      (reporter lacZ gene transfer) treatment. Of further note, administration of the
      SOX9 vector was also capable of delaying premature hypertrophic and osteogenic
      differentiation in the constructs. This enhancement of chondrogenesis by
      spatially defined overexpression of human SOX9 demonstrate the potential benefits
      of using rAAV-modified hMSCs seeded in fibrin-polyurethane scaffolds as a
      promising approach for implantation in focal cartilage lesions to improve
      cartilage repair.

PMID- 30189665
TI  - Exploring the Gas-Permeation Properties of Proton-Conducting Membranes Based on
      Protic Imidazolium Ionic Liquids: Application in Natural Gas Processing.
AB  - This experimental study explores the potential of supported ionic liquid
      membranes (SILMs) based on protic imidazolium ionic liquids (ILs) and randomly
      nanoporous polybenzimidazole (PBI) supports for CH4/N2 separation. In particular,
      three classes of SILMs have been prepared by the infiltration of porous PBI
      membranes with different protic moieties: 1-H-3-methylimidazolium bis
      (trifluoromethane sulfonyl)imide; 1-H-3-vinylimidazolium bis(trifluoromethane
      sulfonyl)imide followed by in situ ultraviolet (UV) polymerization to poly[1-(3H
      imidazolium)ethylene] bis(trifluoromethanesulfonyl)imide. The polymerization
      process has been monitored by Fourier transform infrared (FTIR) spectroscopy and
      the concentration of the protic entities in the SILMs has been evaluated by
      thermogravimetric analysis (TGA). Single gas permeability values of N2 and CH4 at
      313 K, 333 K and 363 K were obtained from a series of experiments conducted in a
      batch gas permeance system. The results obtained were assessed in terms of the
      preferential cavity formation and favorable solvation of methane in the apolar
      domains of the protic ionic network. The most attractive behavior exhibited
      poly[1-(3H-imidazolium)ethylene]bis(trifluoromethanesulfonyl)imide polymeric
      ionic liquid (PIL) cross-linked with 1% divinylbenzene supported membranes,
      showing stable performance when increasing the upstream pressure. The CH4/N2
      permselectivity value of 2.1 with CH4 permeability of 156 Barrer at 363 K
      suggests that the transport mechanism of the as-prepared SILMs is solubility
      dominated.

PMID- 30189668
TI  - Energy-Efficient Forest Fire Prediction Model Based on Two-Stage Adaptive Duty
      Cycled Hybrid X-MAC Protocol.
AB  - This paper proposes an adaptive duty-cycled hybrid X-MAC (ADX-MAC) protocol for
      energy-efficient forest fire prediction. The Asynchronous sensor network
      protocol, X-MAC protocol, acquires additional environmental status details from
      each forest fire monitoring sensor for a given period, and then changes the duty
      cycle sleep interval to efficiently calculate forest fire occurrence risk
      according to the environment. Performance was verified experimentally, and the
      proposed ADX-MAC protocol improved throughput by 19% and was 24% more energy
      efficient compared to the X-MAC protocol. The duty-cycle was shortened as forest
      fire probability increased, ensuring forest fires were detected at faster cycle
      rate.

PMID- 30189666
TI  - Affinity Sensing Strategies for the Detection of Pesticides in Food.
AB  - This is a review of recent affinity-based approaches that detect pesticides in
      food. The importance of the quantification and monitoring of pesticides is
      firstly discussed, followed by a description of the different approaches reported
      in the literature. The different sensing approaches are reported according to the
      different recognition element used: antibodies, aptamers, or molecularly
      imprinted polymers. Schemes of detection and the main features of the assays are
      reported and commented upon. The large number of affinity sensors recently
      developed and tested on real samples demonstrate that this approach is ready to
      be validated to monitor the amount of pesticides used in food commodities.

PMID- 30189667
TI  - A Metabolomics Approach to Pharmacotherapy Personalization.
AB  - The optimization of drug therapy according to the personal characteristics of
      patients is a perspective direction in modern medicine. One of the possible ways
      to achieve such personalization is through the application of "omics"
      technologies, including current, promising metabolomics methods. This review
      demonstrates that the analysis of pre-dose metabolite biofluid profiles allows
      clinicians to predict the effectiveness of a selected drug treatment for a given
      individual. In the review, it is also shown that the monitoring of post-dose
      metabolite profiles could allow clinicians to evaluate drug efficiency, the
      reaction of the host to the treatment, and the outcome of the therapy. A
      comparative description of pharmacotherapy personalization (pharmacogenomics,
      pharmacoproteomics, and therapeutic drug monitoring) and personalization based on
      the analysis of metabolite profiles for biofluids (pharmacometabolomics) is also
      provided.

PMID- 30189669
TI  - A Compact Ultrawideband Antenna Based on Hexagonal Split-Ring Resonator for pH
      Sensor Application.
AB  - A compact ultrawideband (UWB) antenna based on a hexagonal split-ring resonator
      (HSRR) is presented in this paper for sensing the pH factor. The modified HSRR is
      a new concept regarding the conventional square split-ring resonator (SSRR). Two
      HSRRs are interconnected with a strip line and a split in one HSRR is introduced
      to increase the electrical length and coupling effect. The presented UWB antenna
      consists of three unit cells on top of the radiating patch element. This
      combination of UWB antenna and HSRR gives double-negative characteristics which
      increase the sensitivity of the UWB antenna for the pH sensor. The proposed
      ultrawideband antenna metamaterial sensor was designed and fabricated on FR-4
      substrate. The electrical length of the proposed metamaterial antenna sensor is
      0.238 * 0.194 * 0.016 lambda, where lambda is the lowest frequency of 3 GHz. The
      fractional bandwidth and bandwidth dimension ratio were achieved with the
      metamaterial-inspired antenna as 146.91% and 3183.05, respectively. The operating
      frequency of this antenna sensor covers the bandwidth of 17 GHz, starting from 3
      to 20 GHz with a realized gain of 3.88 dB. The proposed HSRR-based ultrawideband
      antenna sensor is found to reach high gain and bandwidth while maintaining the
      smallest electrical size, a highly desired property for pH-sensing applications.

PMID- 30189671
TI  - Dissolving Microneedle Patches for Transdermal Insulin Delivery in Diabetic Mice:
      Potential for Clinical Applications.
AB  - In this study, dissolving polymeric microneedle (MN) patches composed of gelatin
      and sodium carboxymethyl cellulose (CMC) were used to localize insulin. Their in
      vitro skin insertion capabilities were determined using tissue-marking dye to
      stain the skin after patches removal. Scanning electron microscopy (SEM) was used
      to determine changes in the MNs over time, and optical coherence tomography (OCT)
      was used to monitor their real-time penetration depth. Confocal microscopy images
      revealed that rhodamine 6G gradually diffuses from the puncture sites to deeper
      dermal tissue. Using an in vivo imaging system (IVIS), skin areas that received
      FITC-insulin-loaded MNs were found to present strong fluorescent signals that
      greatly decreased 1 h after application. Results show that dissolving MNs rapidly
      release FITC-insulin, and it then gradually diffuses into the skin. This study
      verifies that using a gelatin/CMC MN patch for insulin delivery achieves
      satisfactory relative bioavailability compared to a traditional hypodermic
      injection and can be a promising delivery device for poorly permeable protein
      drugs such as those used to treat diabetes. Insertion tests on human cadaveric
      skin demonstrate that dissolving MNs could serve as efficient devices for
      transdermal drug delivery in clinical practice and that the volar aspect of
      forearm skin is the ideal location for their applications.

PMID- 30189670
TI  - Z Probe, An Efficient Tool for Characterizing Long Non-Coding RNA in FFPE
      Tissues.
AB  - Formalin-fixed paraffin embedded (FFPE) tissues are a valuable resource for
      biomarker discovery in order to understand the etiology of different cancers and
      many other diseases. Proteins are the biomarkers of interest with respect to FFPE
      tissues as RNA degradation is the major challenge in these tissue samples.
      Recently, non-protein coding transcripts, long non-coding RNAs (lncRNAs), have
      gained significant attention due to their important biological actions and
      potential involvement in cancer. RNA sequencing (RNA-seq) or quantitative reverse
      transcription-polymerase chain reaction (qRT-PCR) are the only validated methods
      to evaluate and study lncRNA expression and neither of them provides visual
      representation as immunohistochemistry (IHC) provides for proteins. We have
      standardized and are reporting a sensitive Z probe based in situ hybridization
      method to visually identify and quantify lncRNA in FFPE tissues. This assay is
      highly sensitive and identifies transcripts visible within different cell types
      and tumors. We have detected a scarcely expressed tumor suppressor lncRNA NRON
      (non-coding repressor of nuclear factor of activated T-cells (NFAT)), a
      moderately expressed oncogenic lncRNA UCA1 (urothelial cancer associated 1), and
      a highly studied and expressed lncRNA MALAT1 (metastasis associated lung
      adenocarcinoma transcript 1) in different cancers. High MALAT1 staining was found
      in colorectal, breast and pancreatic cancer. Additionally, we have observed an
      increase in MALAT1 expression in different stages of colorectal cancer.

PMID- 30189672
TI  - Antimicrobial Potential of Silver Nanoparticles Synthesized Using Medicinal Herb
      Coptidis rhizome.
AB  - Coptidis rhizome contains several alkaloids that are bioactive agents of
      therapeutic value. We propose an eco-friendly method to synthesize biocompatible
      silver nanoparticles (AgNPs) using the aqueous extract of Coptidis rhizome.
      Silver ions were reduced to AgNPs using the aqueous extract of Coptidis rhizome,
      indicating that Coptidis rhizome can be used for the biosynthesis of AgNPs. The
      time and the concentration required for conversion of silver ions into AgNPs was
      optimized using UV-absorbance spectroscopy and inductively coupled plasma
      spectroscopy (ICP). Biosynthesized AgNPs showed a distinct UV-Visible absorption
      peak at 420 nm. ICP analysis showed that the time required for the completion of
      biosynthesis was around 20 min. Microscopic images showed that nanoparticles
      synthesized were of spherical shape and the average diameter of biosynthesized
      AgNPs was less than 30 nm. XRD analysis also confirmed the size of AgNps and
      revealed their crystalline nature. The interaction of AgNPs with phytochemicals
      present in Coptidis rhizome extract was observed in FTIR analysis. The
      antimicrobial property of AgNPs was evaluated using turbidity measurements.
      Coptidis rhizome-mediated biosynthesized AgNPs showed significant anti-bacterial
      activities against Escherichia coli and Staphylococcus aureus that are commonly
      involved in various types of infections, indicating their potential as an
      effective anti-bacterial agent.

PMID- 30189673
TI  - Does Information Pattern Affect Risk Perception of Food Safety? A National Survey
      in China.
AB  - Examining the variances in the assessments of risk, as perceived by residents,
      facilitates the development of appropriate risk information communication
      strategies. This paper aims to identify the effects of information source
      patterns on perceived food safety risks based on demographic factors. A national
      survey was conducted to examine, by means of multiple regression analysis, the
      relationship between the public's perceived risks, demographic factors and
      information access. The study finds that residents' preferences for information
      sources have been empirically proven to significantly affect their perceptions of
      food safety. We also find that more educated young urban dwellers, as well as
      those without cohabitation experience, tend to perceive a higher level of risk
      with respect to food safety. In contrast to our expectations, gender, family
      income and family size are not significantly correlated with the perception of
      food safety risk. The findings help to explain residents' attitudes toward food
      safety administration and reactions to food hazards in the Chinese context. It is
      recommended that the governing authorities strengthen their communication
      capacities using modern communication media and make full use of traditional and
      face-to-face communications with respect to regulations.

PMID- 30189674
TI  - The Cooking and Pneumonia Study (CAPS) in Malawi: A Cross-Sectional Assessment of
      Carbon Monoxide Exposure and Carboxyhemoglobin Levels in Children under 5 Years
      Old.
AB  - Household air pollution is estimated to cause half a million deaths from
      pneumonia in children worldwide. The Cooking and Pneumonia Study (CAPS) was
      conducted to determine whether the use of cleaner-burning biomass-fueled
      cookstoves would reduce household air pollution and thereby the incidence of
      pneumonia in young children in rural Malawi. Here we report a cross-sectional
      assessment of carbon monoxide (CO) exposure and carboxyhemoglobin (COHgB) levels
      at recruitment to CAPS. Mean (SD; range) 48-h CO exposure of 1928 participating
      children was 0.90 (2.3; 0-49) ppm and mean (SD; range) COHgB level was 5.8% (3.3;
      0-20.3). Higher mean CO and COHgB levels were associated with location (Chikhwawa
      versus Chilumba) (OR 3.55 (1.73-7.26)); (OR 2.77 (1.08-7.08)). Correlation
      between mean CO and COHgB was poor (Spearman's rho = 0.09, p < 0.001). The
      finding of high COHgB levels in young children in rural Malawi that are at levels
      at which adverse neurodevelopmental and cognitive effects occur is of concern.
      Effective approaches for reducing exposure to CO and other constituents of air
      pollution in rural sub-Saharan African settings are urgently needed.

PMID- 30189675
TI  - Efficiency Enhancement of Perovskite Solar Cells with Plasmonic Nanoparticles: A
      Simulation Study.
AB  - Recently, hybrid organic-inorganic perovskites have been extensively studied due
      to their promising optical properties with relatively low-cost and simple
      processing. However, the perovskite solar cells have some low optical absorption
      in the visible spectrum, especially around the red region. In this paper, an
      improvement of perovskite solar cell efficiency is studied via simulations
      through adding plasmonic nanoparticles (NPs) at the rear side of the solar cell.
      The plasmonic resonance wavelength is selected to be very close to the spectrum
      range of lower absorption of the perovskite: around 600 nm. Both gold and silver
      nanoparticles (Au and Ag NPs) are selected to introduce the plasmonic effect with
      diameters above 40 nm, to get an overlap between the plasmonic resonance spectrum
      and the requested lower absorption spectrum of the perovskite layer. Simulations
      show the increase in the short circuit current density (Jsc) as a result of
      adding Au and Ag NPs, respectively. Enhancement in Jsc is observed as the
      diameter of both Au and Ag NPs is increased beyond 40 nm. Furthermore, there is a
      slight increase in the reflection loss as the thickness of the plasmonic
      nanoparticles at the rear side of the solar cell is increased. A significant
      decrease in the current loss due to transmission is achieved as the size of the
      nanoparticles increases. As a comparison, slightly higher enhancement in external
      quantum efficiency (EQE) can be achieved in case of adding Ag NPs rather than Au
      NPs.

PMID- 30189676
TI  - Therapy and Antifungal Susceptibility Profile of Microsporum canis.
AB  - Microsporum canis is a worldwide diffused zoophilic dermatophyte which causes
      clinical conditions often characterised by multifocal alopecia, scaling, and
      circular lesions in many animal species, including humans. A large variety of
      oral and topical antifungal protocols is available for treating M. canis
      infection. However, the efficacy of these drugs and treatment protocols is
      variable, with treatment failure up to 40% of patients possibly due to resistance
      phenomena. The lack of standardised reference methods for evaluating the
      antifungal susceptibility of M. canis represents a major hindrance in assessing
      microbiological resistance in unresponsive clinical cases. Therefore, data about
      conventional therapy against M. canis and the protocols employed to test the
      antifungal activity of the most commonly employed drugs (i.e., azoles, polyenes,
      allylamines, and griseofulvin) have been summarised herein. This article focuses
      on technical parameters used for antifungal susceptibility tests, their effects
      on the minimum inhibitory concentration value, as well as their clinical
      implications.

PMID- 30189678
TI  - Poly(1-trimethylsilyl-1-propyne)-Based Hybrid Membranes: Effects of Various
      Nanofillers and Feed Gas Humidity on CO2 Permeation.
AB  - Poly(1-trimethylsilyl-1-propyne) (PTMSP) is a high free volume polymer with
      exceptionally high gas permeation rate but the serious aging problem and low
      selectivity have limited its application as CO2 separation membrane material.
      Incorporating inorganic nanoparticles in polymeric membranes has been a common
      approach to improve the separation performance of membranes, which has also been
      used in PTMSP based membrane but mostly with respect to tackling the aging
      issues. Aiming at increasing the CO2 selectivity, in this work, hybrid membranes
      containing four types of selected nanofillers (from 0 to 3D) were fabricated
      using PTMSP as the polymer matrix. The effects of the various types of
      nanofillers on the CO2 separation performance of the resultant membranes were
      systematically investigated in humid conditions. The thermal, chemical and
      morphologic properties of the hybrid membranes were characterized using TGA, FTIR
      and SEM. The gas permeation properties of the hybrid membranes were evaluated
      using mixed gas permeation test with the presence of water vapour to simulate the
      flue gas conditions. Experiments show that the addition of different fillers
      results in significantly different separation performances; The addition of ZIF-L
      porous 2D filler improves the CO2/N2 selectivity at the expenses of CO2
      permeability, while the addition of TiO2, ZIF-7 and ZIF-8 increases the CO2
      permeability but the CO2/N2 selectivity decreases.

PMID- 30189677
TI  - Non-Invasive Assessment of Lactate Production and Compartmentalization in Renal
      Cell Carcinomas Using Hyperpolarized 13C Pyruvate MRI.
AB  - Optimal treatment selection for localized renal tumors is challenging due to
      their variable biological behavior and limited ability to pre-operatively assess
      their aggressiveness. We investigated hyperpolarized (HP) 13C pyruvate MRI to
      noninvasively assess tumor lactate production and compartmentalization, which are
      strongly associated with renal tumor aggressiveness. Orthotopic tumors were
      created in mice using human renal cell carcinoma (RCC) lines (A498, 786-O,
      UOK262) with varying expression of lactate dehydrogenase A (LDHA) which catalyzes
      the pyruvate-to-lactate conversion, and varying expression of monocarboxylate
      transporter 4 (MCT4) which mediates lactate export out of the cells. Dynamic HP
      13C pyruvate MRI showed that the A498 tumors had significantly higher 13C
      pyruvate-to-lactate conversion than the UOK262 and 786-O tumors, corresponding to
      higher A498 tumor LDHA expression. Additionally, diffusion-weighted HP 13C
      pyruvate MRI showed that the A498 tumors had significantly higher 13C lactate
      apparent diffusion coefficients compared to 786-O tumors, with corresponding
      higher MCT4 expression, which likely reflects more rapid lactate export in the
      A498 tumors. Our data demonstrate the feasibility of HP 13C pyruvate MRI to
      inform on tumor lactate production and compartmentalization, and provide the
      scientific premise for future clinical investigation into the utility of this
      technique to noninvasively interrogate renal tumor aggressiveness and to guide
      treatment selection.

PMID- 30189679
TI  - An Advanced Numerical Trajectory Model Tracks a Corn Earworm Moth Migration Event
      in Texas, USA.
AB  - Many methods for trajectory simulation, such as Hybrid Single-Particle Lagrangian
      Integrated Trajectory (HYSPLIT), have been developed over the past several
      decades and contributed greatly to our knowledge in insect migratory movement. To
      improve the accuracy of trajectory simulation, we developed a new numerical
      trajectory model, in which the self-powered flight behaviors of insects are
      considered and trajectory calculation is driven by high spatio-temporal
      resolution weather conditions simulated by the Weather Research and Forecasting
      (WRF) model. However, a rigorous evaluation of the accuracy of different
      trajectory models on simulated long-distance migration is lacking. Hence, in this
      study our trajectory model was evaluated by a migration event of the corn earworm
      moth, Helicoverpazea, in Texas, USA on 20-22 March 1995. The results indicate
      that the simulated migration trajectories are in good agreement with occurrences
      of all pollen-marked male H.zea immigrants monitored in pheromone traps.
      Statistical comparisons in the present study suggest that our model performed
      better than the popularly-used HYSPLIT model in simulating migration trajectories
      of H.zea. This study also shows the importance of high-resolution atmospheric
      data and a full understanding of migration behaviors to the computational design
      of models that simulate migration trajectories of highly-flying insects.

PMID- 30189680
TI  - Detection of Glyphosate in Drinking Water: A Fast and Direct Detection Method
      without Sample Pretreatment.
AB  - Glyphosate (Gly) is one of the most problematic pesticides that repeatedly
      appears in drinking water. Continuous on-site detection of Gly in water supplies
      can provide an early warning in incidents of contamination, before the pesticide
      reaches the drinking water. Here, we report the first direct detection of Gly in
      tap water with electrochemical sensing. Gold working electrodes were used to
      detect the pesticide in spiked tap water without any supporting electrolyte,
      sample pretreatment or electrode modifications. Amperometric measurements were
      used to quantify Gly to a limit of detection of 2 MUM, which is below the
      regulation limit of permitted contamination of drinking water in the United
      States. The quantification of Gly was linearly proportional with the measured
      signal. The selectivity of this method was evaluated by applying the same
      technique on a Gly Metabolite, AMPA, and on another pesticide, omethoate, with a
      chemical structure similar to Gly. The testing revealed no interfering
      electrochemical activity at the potential range used for Gly detection. The
      simple detection of Gly presented in this work may lead to direct on-site
      monitoring of Gly contamination at drinking water sources.

PMID- 30189681
TI  - Antimicrobial Potential of Silver Nanoparticles Synthesized Using Medicinal Herb
      Coptidis rhizome.
AB  - Coptidisrhizome contains several alkaloids that are bioactive agents of
      therapeutic value. We propose an eco-friendly method to synthesize biocompatible
      silver nanoparticles (AgNPs) using the aqueous extract of Coptidisrhizome. Silver
      ions were reduced to AgNPs using the aqueous extract of Coptidisrhizome,
      indicating that Coptidisrhizome can be used for the biosynthesis of AgNPs. The
      time and the concentration required for conversion of silver ions into AgNPs was
      optimized using UV-absorbance spectroscopy and inductively coupled plasma
      spectroscopy (ICP). Biosynthesized AgNPs showed a distinct UV-Visible absorption
      peak at 420 nm. ICP analysis showed that the time required for the completion of
      biosynthesis was around 20 min. Microscopic images showed that nanoparticles
      synthesized were of spherical shape and the average diameter of biosynthesized
      AgNPs was less than 30 nm. XRD analysis also confirmed the size of AgNps and
      revealed their crystalline nature. The interaction of AgNPs with phytochemicals
      present in Coptidisrhizome extract was observed in FTIR analysis. The
      antimicrobial property of AgNPs was evaluated using turbidity measurements.
      Coptidisrhizome-mediated biosynthesized AgNPs showed significant anti-bacterial
      activities against Escherichia coli and Staphylococcus aureus that are commonly
      involved in various types of infections, indicating their potential as an
      effective anti-bacterial agent.

PMID- 30189682
TI  - Numerical Simulation and FRAP Experiments Show That the Plasma Membrane Binding
      Protein PH-EFA6 Does Not Exhibit Anomalous Subdiffusion in Cells.
AB  - The fluorescence recovery after photobleaching (FRAP) technique has been used for
      decades to measure movements of molecules in two-dimension (2D). Data obtained by
      FRAP experiments in cell plasma membranes are assumed to be described through a
      means of two parameters, a diffusion coefficient, D (as defined in a pure
      Brownian model) and a mobile fraction, M. Nevertheless, it has also been shown
      that recoveries can be nicely fit using anomalous subdiffusion. Fluorescence
      recovery after photobleaching (FRAP) at variable radii has been developed using
      the Brownian diffusion model to access geometrical characteristics of the
      surrounding landscape of the molecule. Here, we performed numerical simulations
      of continuous time random walk (CTRW) anomalous subdiffusion and interpreted them
      in the context of variable radii FRAP. These simulations were compared to
      experimental data obtained at variable radii on living cells using the pleckstrin
      homology (PH) domain of the membrane binding protein EFA6 (exchange factor for
      ARF6, a small G protein). This protein domain is an excellent candidate to
      explore the structure of the interface between cytosol and plasma membrane in
      cells. By direct comparison of our numerical simulations to the experiments, we
      show that this protein does not exhibit anomalous diffusion in baby hamster
      kidney (BHK) cells. The non Brownian PH-EFA6 dynamics observed here are more
      related to spatial heterogeneities such as cytoskeleton fence effects.

PMID- 30189684
TI  - A Homogeneous Breast Phantom Measurement System with an Improved Modified
      Microwave Imaging Antenna Sensor.
AB  - Microwave breast imaging has been reported as having the most potential to become
      an alternative or additional tool to the existing X-ray mammography technique for
      detecting breast tumors. Microwave antenna sensor performance plays a significant
      role in microwave imaging system applications because the image quality is mostly
      affected by the microwave antenna sensor array properties like the number of
      antenna sensors in the array and the size of the antenna sensors. In this paper,
      a new system for successful early detection of a breast tumor using a balanced
      slotted antipodal Vivaldi Antenna (BSAVA) sensor is presented. The designed
      antenna sensor has an overall dimension of 0.401lambda * 0.401lambda *
      0.016lambda at the first resonant frequency and operates between 3.01 to 11 GHz
      under 10 dB. The radiating fins are modified by etching three slots on both fins
      which increases the operating bandwidth, directionality of radiation pattern,
      gain and efficiency. The antenna sensor performance of both the frequency domain
      and time domain scenarios and high-fidelity factor with NFD is also investigated.
      The antenna sensor can send and receive short electromagnetic pulses in the near
      field with low loss, little distortion and highly directionality. A realistic
      homogenous breast phantom is fabricated, and a breast phantom measurement system
      is developed where a two antennas sensor is placed on the breast model rotated by
      a mechanical scanner. The tumor response was investigated by analyzing the
      backscattering signals and successful image construction proves that the proposed
      microwave antenna sensor can be a suitable candidate for a high-resolution
      microwave breast imaging system.

PMID- 30189685
TI  - Supported Bimetallic AuPd Nanoparticles as a Catalyst for the Selective
      Hydrogenation of Nitroarenes.
AB  - The solvent-free selective hydrogenation of nitrobenzene was carried out using a
      supported AuPd nanoparticles catalyst, prepared by the modified impregnation
      method (MIm), as efficient catalyst >99% yield of aniline (AN) was obtained after
      15 h at 90  degrees C, 3 bar H2 that can be used without any further purification
      or separation, therefore reducing cost and energy input. Supported AuPd
      nanoparticles catalyst, prepared by MIm, was found to be active and stable even
      after four recycle experiments, whereas the same catalyst prepared by SIm was
      deactivated during the recycle experiments. The most effective catalyst was
      tested for the chemoselective hydrogenation of 4-chloronitrobenzene (CNB) to 4
      chloroaniline (CAN). The activation energy of CNB to CAN was found to be 25 kJ
      mol-1, while that of CNB to AN was found to be 31 kJ mol-1. Based on this, the
      yield of CAN was maximized (92%) by the lowering the reaction temperature to 25 
      degrees C.

PMID- 30189686
TI  - Fabrication of Mo-Doped WO3 Nanorod Arrays on FTO Substrate with Enhanced
      Electrochromic Properties.
AB  - Well-oriented and crystalline WO3 nanorod arrays (WNRAs) decorated with Mo were
      synthesized on fluorine doped tin oxide (FTO) substrate by the hydrothermal
      method. The effects of Mo doping, hydrothermal reaction time, and hydrothermal
      temperature on the morphologies and electrochromic properties of as-prepared
      WNRAs were studied thoroughly. Scanning electron microscopy (SEM), energy
      dispersive spectrometry (EDS), X-ray diffraction (XRD), X-ray photoelectron
      spectroscopy (XPS), and chronoamperometry techniques were used to characterize
      the structures and properties of obtained WNRAs. The results demonstrate that the
      average diameter of the as-prepared WNRAs ranged from 30 to 70 nm. During the
      decoration of Mo on the WNRAs, the growth density of as-prepared WNRAs decreased
      and the surfaces became rough. However, the decorated Mo on WNRAs synthesized at
      180  degrees C for 5 h with a Mo/W mole ratio of 1:40 exhibited better
      electrochromic properties than single WNRAs. They exhibited high optical
      modulation (61.7%), fast bleaching/coloring response times (3 s/9 s), high
      coloration efficiency values (73.1 cm2/C), and good cycling stability.

PMID- 30189683
TI  - Thermo-Sensitive Vesicles in Controlled Drug Delivery for Chemotherapy.
AB  - Thermo-sensitive vesicles are a promising tool for triggering the release of
      drugs to solid tumours when used in combination with mild hyperthermia.
      Responsivity to temperature makes them intelligent nanodevices able to provide a
      site-specific chemotherapy. Following a brief introduction concerning
      hyperthermia and its advantageous combination with vesicular systems, recent
      investigations on thermo-sensitive vesicles useful for controlled drug delivery
      in cancer treatment are reported in this review. In particular, the influence of
      bilayer composition on the in vitro and in vivo behaviour of thermo-sensitive
      formulations currently under investigation have been extensively explored.

PMID- 30189687
TI  - Two-Holder Strategy for Efficient and Selective Synthesis of Lk 1 ssDNA Catenane.
AB  - DNA catenanes are characterized by their flexible and dynamic motions and have
      been regarded as one of the key players in sophisticated DNA-based molecular
      machines. There, the linking number (Lk) between adjacent interlocked rings is
      one of the most critical factors, since it governs the feasibility of dynamic
      motions. However, there has been no established way to synthesize catenanes in
      which Lk is controlled to a predetermined value. This paper reports a new
      methodology to selectively synthesize Lk 1 catenanes composed of single-stranded
      DNA rings, in which these rings can most freely rotate each other due to minimal
      inter-ring interactions. To the mixture for the synthesis, two holder strands
      (oligonucleotides of 18-46 nt) were added, and the structure of the quasi
      catenane intermediate was interlocked through Watson-Crick base pairings into a
      favorable conformation for Lk 1 catenation. The length of the complementary part
      between the two quasi-rings was kept at 10 bp or shorter. Under these steric
      constraints, two quasi-rings were cyclized with the use of T4 DNA ligase. By this
      simple procedure, the formation of undesired topoisomers (Lk >= 2) was almost
      completely inhibited, and Lk 1 catenane was selectively prepared in high yield up
      to 70 mole%. These Lk 1 catenanes have high potentials as dynamic parts for
      versatile DNA architectures.

PMID- 30189688
TI  - Correction: Esparham, A., et al., Pediatric Integrative Medicine: Vision for the
      Future. Children, 2018, 5, 111.
AB  - The authors wish to make the following corrections to their paper [...].

PMID- 30189690
TI  - Fluorescent Nanosensor Based on Molecularly Imprinted Polymers Coated on Graphene
      Quantum Dots for Fast Detection of Antibiotics.
AB  - In this work, we developed a novel fluorescent sensor by combining molecularly
      imprinted polymers (MIPs) with graphene quantum dots (GQDs) for the determination
      of tetracycline (TC) in aqueous samples. Firstly, we developed a one-pot green
      method to synthesize GQDs as the fluorescent probes. GQDs with carboxyl groups or
      amino groups were fabricated. It was found that carboxyl groups played an
      important role in the fluorescence quenching. Based on these findings, the GQDs
      MIPs microspheres were prepared using a sol-gel process. GQDs-MIPs showed strong
      fluorescent emission at 410 nm when excited at 360 nm, and the fluorescence was
      quenched in the presence of TC. Under optimum conditions, the fluorescence
      intensity of GQDs-MIPs decreased in response to the increase of TC concentration.
      The linear rage was from 1.0 to 104 ug.L-1, and the limit of detection was
      determined to be 1 ug.L-1. The GQDs-MIPs also demonstrated high selectivity
      towards TC. The fluorescent sensor was successfully applied for the detection of
      TC in real spiked milk samples.

PMID- 30189689
TI  - Novel Riboflavin-Inspired Conjugated Bio-Organic Semiconductors.
AB  - Flavins are known to be extremely versatile, thus enabling routes to innumerable
      modifications in order to obtain desired properties. Thus, in the present paper,
      the group of bio-inspired conjugated materials based on the alloxazine core is
      synthetized using two efficient novel synthetic approaches providing relatively
      high reaction yields. The comprehensive characterization of the materials, in
      order to evaluate the properties and application potential, has shown that the
      modification of the initial alloxazine core with aromatic substituents allows
      fine tuning of the optical bandgap, position of electronic orbitals, absorption
      and emission properties. Interestingly, the compounds possess multichromophoric
      behavior, which is assumed to be the results of an intramolecular proton
      transfer.

PMID- 30189692
TI  - An Automatic User Activity Analysis Method for Discovering Latent Requirements:
      Usability Issue Detection on Mobile Applications.
AB  - Starting with the Internet of Things (IoT), new forms of system operation
      concepts have emerged to provide creative services through collaborations among
      autonomic devices. Following these paradigmatic changes, the ability of each
      participating system to automatically diagnose the degree of quality it is
      providing is inevitable. This paper proposed a method to automatically detect
      symptoms that hinder certain quality attributes. The method consisted of three
      steps: (1) extracting information from real usage logs and automatically
      generating an activity model from the captured information; (2) merging multiple
      user activity models into a single, representative model; and (3) detecting
      differences between the representative user activity model, and an expected
      activity model. The proposed method was implemented in a domain-independent
      framework, workable on the Android platform. Unlike other related works, we used
      quantitative evaluation results to show the benefits of applying the proposed
      method to five Android-based, open-source mobile applications. The evaluation
      results showed that the average precision rate for the automatic detection of
      symptoms was 70%, and the success rate for user implementation of usage scenarios
      demonstrated an improvement of around 21%, when the automatically detected
      symptoms were resolved.

PMID- 30189691
TI  - PNPLA3 rs738409 Polymorphism Predicts Development and Severity of Hepatic
      Steatosis but Not Metabolic Syndrome in Celiac Disease.
AB  - Metabolic syndrome (MS) and hepatic steatosis (HS) have been described in
      patients with celiac disease (CD) after starting a gluten-free diet (GFD), but
      data on predictive factors for these conditions are scarce. Recently, the patatin
      like phospholipase domain-containing protein 3 (PNPLA3) rs738409 has been
      identified as a key factor for HS development in the general population. The aim
      of the study was to evaluate the role of PNPLA3 rs738409 in the development of MS
      and HS in CD patients after starting GFD. Between June 2014 and September 2016,
      we consecutively enrolled CD patients with HS, while those without steatosis
      served as a control group. All patients underwent anthropometric and serologic
      investigations, ultrasonography (US) to assess the degree and severity of HS, and
      genotyping of the PNPLA3 rs738409 polymorphism. Finally, 370 subjects were
      enrolled (136 with and 234 without HS). At genotyping assays, the CC genotype was
      found in 194 subjects (52.4%), the CG genotype in 138 subjects (37.3%), and the
      GG genotype in 38 subjects (10.2%). At binary logistic regression, only CG and GG
      alleles were predictive for the development of HS (odds ratio (OR) 1.97; p < 0.01
      for CG and OR 6.9; p < 0.001 for GG). Body mass index (BMI) (OR 3.8; p < 0.001)
      and waist circumference (OR 2.8; p = 0.03) at CD diagnosis were the only
      independent factors for the development of MS. Intergroup comparisons showed that
      the severe grade of HS was more frequently observed in GG than in CC carriers
      (74% vs. 11.3%, p < 0.001, OR 21.8). PNPLA3 CG and GG carriers with CD have a
      higher susceptibility to hepatic steatosis, but not to metabolic syndrome.
      Moreover, patients with GG alleles display more severe forms of HS based on
      ultrasound.

PMID- 30189694
TI  - Miliary Tuberculosis Presenting with Hyponatremia and ARDS in an 82-Year-Old
      Immunocompetent Female.
AB  - An immunocompetent 82-year-old female was admitted to our hospital due to fever
      without clear origin and hyponatremia. In the following days, an acute and
      bilateral pulmonary infiltrate appeared with a progressive worsening in
      respiratory function. Chest x-ray and CT (Computed tomography) showed bilateral
      reticulonodular infiltrates. Bronchoscopic aspiration and bronchoalveolar lavage
      (BAL), and transbronchial lung biopsy (TBBX) studies did not reveal
      microbiological and histopathological diagnosis. Broad-spectrum antibiotics were
      non-effective, and the patient died due to respiratory failure. Necropsy study
      revealed a miliary tuberculosis affecting lungs, liver, bone marrow, spleen,
      kidney, arteries, pancreas, and adrenal glands. Some weeks after the patient's
      death, mycobacterial cultures from sputum, BAL and TBBX samples were positive for
      Mycobacterium tuberculosis.

PMID- 30189695
TI  - On the Sensitivity of the Parameters of the Intensity-Based Stochastic Model for
      Terrestrial Laser Scanner. Case Study: B-Spline Approximation.
AB  - For a trustworthy least-squares (LS) solution, a good description of the
      stochastic properties of the measurements is indispensable. For a terrestrial
      laser scanner (TLS), the range variance can be described by a power law function
      with respect to the intensity of the reflected signal. The power and scaling
      factors depend on the laser scanner under consideration, and could be accurately
      determined by means of calibrations in 1d mode or residual analysis of LS
      adjustment. However, such procedures complicate significantly the use of
      empirical intensity models (IM). The extent to which a point-wise weighting is
      suitable when the derived variance covariance matrix (VCM) is further used in a
      LS adjustment remains moreover questionable. Thanks to closed loop simulations,
      where both the true geometry and stochastic model are under control, we
      investigate how variations of the parameters of the IM affect the results of a LS
      adjustment. As a case study, we consider the determination of the Cartesian
      coordinates of the control points (CP) from a B-splines curve. We show that a
      constant variance can be assessed to all the points of an object having
      homogeneous properties, without affecting the a posteriori variance factor or the
      loss of efficiency of the LS solution. The results from a real case scenario
      highlight that the conclusions of the simulations stay valid even for more
      challenging geometries. A procedure to determine the range variance is proposed
      to simplify the computation of the VCM.

PMID- 30189696
TI  - Sotto voce.

PMID- 30189693
TI  - Effects of Inflammation on Biomarkers of Vitamin A Status among a Cohort of
      Bolivian Infants.
AB  - Globally, vitamin A deficiency (VAD) affects nearly 200 million children with
      negative health consequences. VAD can be measured by a retinol-binding protein
      (RBP) and serum retinol concentrations. Their concentrations are not always
      present in a 1:1 molar ratio and are affected by inflammation. This study sought
      to quantify VAD and its impact on infant mortality and infectious morbidity
      during the first 18 months of life in a cohort of mother-infant dyads in El Alto,
      Bolivia, while accounting for the previously mentioned measurement issues.
      Healthy mother-infant dyads (n = 461) were enrolled from two hospitals and
      followed for 12 to 18 months. Three serum samples were collected (at one to two,
      six to eight, and 12 to 18 months of infant age) and analyzed for RBP, and a
      random 10% subsample was analyzed for retinol. Linear regression of RBP on
      retinol was used to generate RBP cut-offs equivalent to retinol <0.7 umol/L. All
      measures of RBP and retinol were adjusted for inflammation, which was measured by
      a C-reactive protein and alpha (1)-acid glycoprotein serum concentrations using
      linear regression. Infant mortality and morbidity rates were calculated and
      compared by early VAD status at two months of age. Retinol and RBP were weakly
      affected by inflammation. This association varied with infant age. Estimated VAD
      (RBP < 0.7 umol/L) decreased from 71.0% to 14.8% to 7.7% at two, six to eight,
      and 12 to 18 months of age. VAD was almost nonexistent in mothers. Early VAD was
      not significantly associated with infant mortality or morbidity rates. This study
      confirmed a relationship between inflammation and vitamin A biomarkers for some
      subsets of the population and suggested that the vitamin A status in early
      infancy improves with age and may not have significantly affected morbidity in
      this population of healthy infants.

PMID- 30189697
TI  - Eliminating parental consent for adolescents receiving human papillomavirus
      vaccination.
AB  - Human papillomavirus (HPV) is a sexually transmitted infection (STI) causing
      nearly all cases of cervical carcinoma and genital condyloma worldwide. While HPV
      vaccination rates are higher in Rhode Island compared to other states, still 27%
      of female adolescents are not fully vaccinated. The requirement for parental
      consent for vaccination administration poses a barrier to HPV vaccine uptake and
      hinders adolescent autonomy. This requirement lies in stark contrast to the goals
      of the Family Planning Title X Program, which provides all adolescents with
      access to contraception and STI prevention and treatment without parental
      consent. In this commentary, we propose that HPV vaccination should be available
      to all pre-teens and adolescents as part of teen reproductive and sexual
      healthcare, and thus be exempt from parental consent in a similar way to other
      reproductive and sexual health services such as STI testing and contraception.
      [Full article available at http://rimed.org/rimedicaljournal-2018-09.asp].

PMID- 30189699
TI  - Evaluation of Orthopaedic Interest Groups in American Medical Schools.
AB  - BACKGROUND: Orthopaedic interest groups (OIGs) are student-run organizations that
      can provide medical students with early exposure to orthopaedic surgery. OIGs can
      serve as venues for musculoskeletal education, clinical experiences, and
      mentorship to students with otherwise limited access to orthopaedics. The purpose
      of this study was to evaluate the prevalence and opportunities offered by OIGs.
      METHODS: The websites of all allopathic medical schools in the United States were
      evaluated. Each website was examined for an established OIG and any pertinent
      information regarding shadowing, research opportunities, lectures, workshops, or
      opportunities to interact with residents. OIGs were categorized based on the
      number and type of offerings provided to their members. RESULTS: Of the 141
      allopathic medical school websites evaluated, 108 (108/141, 76%) had evidence of
      an orthopaedic interest group. Sixty-nine (69/108, 64%) of these schools
      described the opportunities provided. The most common opportunities were clinical
      skills workshops (41/69, 59%), lectures (32/69, 46%), and opportunities to
      interact with current residents (30/69, 43%). The majority of OIGs (39/69, 57%)
      offered fewer than half of the possible opportunities and only 6 groups (9%)
      offered all five opportunities. CONCLUSION: The majority of allopathic medical
      schools in the United States have an OIG; however, the opportunities provided to
      orthopaedic interest group members vary widely from institution to institution.

PMID- 30189698
TI  - Newborn Screening for Hemoglobinopathies in Rhode Island, 2017.
AB  - BACKGROUND: Newborn screening (NBS) is a national initiative for early
      identification of serious illnesses, the clinical consequences of which can be
      reduced by disease-specific early interventions. The Rhode Island Department of
      Health (RIDOH) has been screening for sickle cell disease (SCD) since 1990. In
      this work the authors sought to determine the success of NBS and explore aspects
      of the program that could be improved. METHODS: A convenience sample of PCPs with
      privileges at Women and Infants Hospital of Rhode Island was surveyed by a Survey
      Monkey(r) questionnaire to determine exactly how NBS results were handled in each
      PCP's office and to gather information on how to improve the process as it
      currently stands. RESULTS: The process appeared to work efficiently.
      Recommendations were made to improve the service, examples of which are provided
      with this paper. DISCUSSION: Although NBS has a national focus, the
      responsibility of ensuring that babies are screened successfully and that follow
      up is complete, rests with individual states. This study revealed that the
      screening process in Rhode Island for SCD is successful but provided suggestions
      for improvements. The investigators have followed up with the suggestions.

PMID- 30189700
TI  - State Unintentional Drug Overdose Reporting Surveillance: Opioid Overdose Deaths
      and Characteristics in Rhode Island.
AB  - Unintentional opioid overdoses are a growing public health epidemic in the United
      States. Rhode Island is also faced with a challenging crisis of drug overdose
      deaths. The State Unintentional Drug Overdose Reporting Surveillance (SUDORS)
      data from the second half of 2016 were used to present opioid overdose deaths and
      characteristics in Rhode Island. During July-December 2016, 142 individuals died
      of opioid overdose in Rhode Island. People who died by opioid overdose were more
      likely to be 25-65 years old, male, and non-Hispanic white. The most common
      precipitating circumstances were substance abuse (88%), current mental health
      problems (43%), and physical health problems (27.5%). Over 83% of decedents had 2
      or more substances attribute to causing their death, with fentanyl (71.1%) as the
      most common substance. Only 36.6% of decedents had naloxone administered. Fatal
      opioid overdose data are important for understanding this public health crisis
      and can guide overdose intervention efforts.

PMID- 30189701
TI  - Food Insecurity and Child Maltreatment: A Quality Improvement Project.
AB  - Food insecurity affects both children and adults in 8% of households in the
      United States and 12.8% of households in Rhode Island, negatively impacting
      childhood health and development. Children with a history of child abuse or
      neglect are at higher risk for food insecurity than other pediatric populations.
      Patients evaluated at a child protection clinic - which completes evaluations for
      all forms of suspected child maltreatment - were screened for food insecurity
      using a validated two-item questionnaire. Data were collected over a four-month
      period, with three quality improvement cycles. A quality improvement cycle is a
      planned sequence of systematic and documented activities aimed at improving a
      process. Prior to the implementation of this protocol, children in the clinic
      were not screened for food insecurity. With the initiation of food insecurity
      screening, 8% of all households eligible for screening were found to be food
      insecure. Pediatric providers should identify food insecurity in their patients,
      including in subspecialty care clinics, to optimize care for pediatric patients
      and their families. When food insecurity is identified, referral to resources and
      support services is important.

PMID- 30189702
TI  - Engaging College-Level Baccalaureate-MD Students in Clinical Research.
AB  - College students in baccalaureate-MD (BA/MD) programs are well situated to get
      involved with clinical research as a component of their scholarly enrichment. The
      authors review the educational and professional development benefits of BA/MD
      college research in the United States (US), the lack of evidence-based strategies
      to guide program innovation, lessons from non-US medical school research
      enrichment efforts, and teaching models that can help boost BA/MD research
      engagement at the college level. Collaboration on part of program directors,
      faculty and students can help strengthen the quality and accessibility of
      research opportunities with a focus on longitudinal skills building and
      professional mentorship.

PMID- 30189703
TI  - Use of Language Services for Telephone Advice by Limited English Proficiency
      Families in a Pediatric Primary Care Setting.
AB  - BACKGROUND: Families limited in English proficiency (LEP) often do not receive
      appropriate medical language services, resulting in health disparities. Little is
      known about the use and effectiveness of language services provided via telephone
      when families call for medical advice. OBJECTIVE: To characterize language
      service provision to LEP families calling for medical advice in a pediatric
      primary care setting. METHODS: A self-administered survey was given to parents of
      children presenting for sick visits at an urban academic pediatric primary care
      practice. RESULTS: 277 out of 300 surveys were completed, 92% in English and 8%
      in Spanish. 7% (19/271) of those who answered the language proficiency question
      reported LEP (spoke English "not well," or "not at all"). Among LEP parents, 68%
      calling for advice during clinic hours received appropriate language services (a
      trained interpreter or a bilingual provider). 53% received these services when
      calling after hours. CONCLUSIONS: Over half of LEP families seeking telephone
      advice from their pediatric primary care office received adequate language
      services. Future research should identify barriers to providing telephone
      language services to LEP families.

PMID- 30189704
TI  - Comparing HbA1C by POC and HPLC.
AB  - OBJECTIVE: Point-of-care (POC) Hemoglobin A1C (HbA1C) testing is frequently used
      to assess glycemic control in diabetes management. Studies are lacking on the
      comparison of POC with high performance liquid chromatography (HPLC) when the POC
      HbA1C is >= 14%. METHODS: Retrospective chart review of children with T1DM at
      Rhode Island Hospital from 2007-2013. Primary objective was to delineate the
      range of HPLC HbA1C values when the POC is >= 14% and characterize these
      patients. PRIMARY RESULTS: There were 72 patients, 5-21 years old, with
      corresponding POC and HPLC tests. Nineteen children, mean age 16.1 years, had a
      POC HbA1C >= 14%. Their mean HPLC value was 14.1% (95% CI [13.4, 14.8]), with
      range 11.1-16.3 and standard deviation 1.4%. CONCLUSION: There is wide variation
      when POC HbA1C values are >= 14%. We suggest routine central HbA1C testing when
      the POC is >= 14% for proper counseling and follow-up of glycemic control.
      Tracking relative changes in HbA1C at subsequent clinic visits is important as it
      allows clinicians to gauge whether or not interventions are effective.
      Additionally, knowledge that their HbA1C is trending down may provide positive
      reinforcement to adolescents.

PMID- 30189705
TI  - Risky Motor Vehicle Behaviors among Rhode Island High School Students.

PMID- 30189706
TI  - Changes in the fat body and oocysts during starvation and vitellogenesis in a
      mosquito, Aedes aegypti (L.).
AB  - When Aedes aegypti females first emerge as adults, their oocytes possess no yolk.
      The abdominal fat body cells contain large quantities of lipid, protein, and
      glycogen, and possess many free ribosomes, but have very little rough endoplasmic
      reticulum (RER). When the females are starved for four days, their oocytes form
      fine lipid and protein yolk endogenously, the latter being located mainly around
      the nucleus. The adipocytes in these fasted mosquitoes have greatly reduced
      amounts of lipid, protein and glycogen and contain many cytolysosomes. Seven
      hours after 4-day-starved females had fed on blood, their oocytes begin filling
      with exogenous protein yolk at the oolemma, and lipid arises endogenously
      throughout the ooplasm. At this hour, the fat cells have synthesized more RER
      than is seen in unfed controls. Twenty-four hours post blood meal, the follicle
      cells have secreted discrete endochorionic plaques onto the oolemma. At this
      period, the adipocytes are densely filled with RER, and show for the first time
      many Golgi bodies and protein inclusions. They have noticeably less glycogen than
      at seven hours. Within 48 hours after mosquitoes have fed on blood, the
      endochorion forms a continuous layer around the steadily enlarging egg which is
      synthesizing additional protein and lipid yolk. Concurrently, the adipocytes show
      a greatly increased amount of glycogen and a significant reduction of RER. By the
      sixtieth hour after the blood meal, the follicle cells are attenuated, and the
      fat cells have less RER and more glycogen than at 48 hours. The nurse cells
      steadily decrease in size during vitellogenesis and release material onto the
      micropyle.

PMID- 30189707
TI  - Time-lapse cinemicrographic studies of cell motility during morphogenesis of the
      embryonic yolk sac of Fundulus heteroclitus (Pisces: Teleosti).
AB  - The active motility of the cells of the yolk sac of the living Fundulus embryo
      was studied by time-lapse cinemicrography with phase contrast optics. In the
      teleost, the yolk sac lies peripheral to the body of the embryo proper and
      consists of a fluid-filled space bounded above by a superficial epithelium, the
      enveloping layer (EVL), and below by the yolk syncytial layer (YSL). The cell
      types treated in the present study are the enveloping layer epithelial cell, the
      stellate cell which lies in a layer flattened on the inner surface of the EVL,
      the epithelioid deep cell, the yolk sac amoebocyte, the yolk sac endothelial cell
      and the yolk sac melanoblast. The most actively motile cells examined in the
      present study are the yolk sac amebocyte and the melanoblast, which emigrates
      from the embryo proper at stages 19-21. The amoebocytes are compact rounded cells
      that move very rapidly by the extension of lamellipods with scalloped margins.
      The amoebocytes wander over the yolk sac in an apparently undirected fashion and
      invade the embryo proper when they happen to encounter it, moving between cells
      of the lateral mesoderm. The melanoblasts migrate by the gradual extension of
      elongated branching processes. Cells are sometimes monopodial, with movement
      being parallel to the long axis of the cell. Alternatively, movement may be
      perpendicular to the predominant long axis, with processes being extended
      alternatively from opposite ends of the cell obliquely forward, so the path
      described is a zig-zag to either side of the overall direction of movement.
      Although the melanoblasts show irregularity in their movement, the predominant
      direction of initial movement is away from the embryo proper. The major yolk sac
      blood vessels form in situ by the collective activities of presumptive
      endothelial cells that enclose volumes of the yolk sac space with sheet-like
      processes from the cell body and from the extensions that connect cells into
      networks.

PMID- 30189708
TI  - Ultrastructural analysis of the morphology and function of the spermatheca of the
      pulmonate snail, Sonorella santaritana.
AB  - The ultrastructure of the spermatheca of the reproductive tract in the pulmonate
      snail, Sonorella santaritana, was investigated. This organ has a debris-filled
      lumen and an outer wall which can be divided into three distinct layers. The cell
      layer adjacent to the lumen is comprised of two cell types, tall columnar
      epithelial cells with microvilli and cells lacking microvilli. The next layer
      also has two cell types, muscle cells and apparent pigment cells. The most
      distant layer is an adventitia of large glycogen-containing cells. The lumen of
      the spermatheca contains a core of partially digested sperm and related
      materials. The luminal contents and the cellular morphology of this organ suggest
      that the spermathecal functions are both digestive and absorptive. It is proposed
      that excess sperm and related materials are transported to the spermatheca,
      digested, and the usable products are reabsorbed.

PMID- 30189709
TI  - Ultrastructural study on cocoon formation in the freshwater oligochaete, Tubifex
      hattai.
AB  - The clitellar epithelium of the freshwater oligochaete, Tubifex hattai, is
      composed of four types of gland cells (Type I, II, III, and IV), in addition to
      the cells generally found in the epidermis of this worm. The possible function of
      these gland cells in cocoon formation was studied with the electron microscope.
      Type I cells discharge their secretory granules by means of compound exocytosis
      and provide the materials for the future cocoon membrane. Immediately after
      completion of the discharge from Type I cells, Type II and III cells
      simultaneously discharge their secretory granules by means of compound
      exocytosis. The secretions from Type II cells constitute a colloid in the cocoon
      lumen and probably cause structural modifications in the future cocoon membrane.
      The secretory products from Type III cells form the cocoon plug. Although the
      process of discharge of secretory granules from Type IV cells was not observed,
      the contribution of these cells to the cocoon formation, producing hoops on the
      outer surface of the future cocoon membrane and fixing its anterior ends on the
      clitellum, is inferred from a morphological comparison of the hoop and the
      structure of the secretory granules.

PMID- 30189710
TI  - Ultrastructure of the y-organs of Cancer antennarius in normal and de-eyestalked
      crabs.
AB  - The paired Y-organs of crustaceans control the molting process. In males of C.
      antennarius, these glands are opalescent, lobulated, epithelioid structures
      embedded in brown fatty tissue. Cells in the periphery extend processes to the
      connective tissue capsule, an arrangement that suggests increased surface area
      for metabolic exchange. The processes contain mitochondria and are tipped
      distally with electron dense material. The cytoplasm, scarce relative to nuclear
      volume, contains vesicles, polymorphic mitochondria with tubular cristae, and
      numerous free ribosomes, but little in way of smooth or rough endoplasmic
      reticulum or Golgi complexes. Progressing from intermolt to the premolt stage,
      mitochondria, as well as vesicles, and electron-dense particles in peripheral
      processes increase somewhat in number. Also, heterochromatin masses concentrate
      adjacent to the nuclear envelope. Eyestalk removal, which induces premolt stages
      in some species, did not produce consistent change in Y-organ substructure in C.
      antennarius. Although evidence is accumulating that Y-organs secrete a steroid
      molting hormone during late intermolt-premolt, the substructure of the glands
      exhibits neither (a) striking changes with the molt cycle, nor (b) all the
      characteristics typical of vertebrate steroid hormone synthesizing glands.
      Nevertheless, the structural features, respectively, are consistent with
      biochemical evidence that Y-organs (a) rapidly take up and convert sterol
      precursor and secrete a product without its accumulation or change in total
      sterol pool size, and (b) apparently cannot synthesize the sterol precursor. Y
      organ cytology closely resembles that of some vertebrate steroid hormone
      secreting glands in which this synthetic capacity is minimal.

PMID- 30189711
TI  - Transformation of the endostyle of the anadromous sea lamprey, Petromyzon marinus
      L., during metamorphosis. II. Electron microscopy.
AB  - Electron microscopy was used to follow the transformation of the endostyle to a
      thyroid gland in the anadromous sea lamprey, Petromyzon marinus L., throughout
      metamorphosis (stages 1-7). Transformation of the larval (ammocoete) endostyle
      begins at the first signs of external change (stages 1-2), and the adult form of
      the gland is reached by stage 5. Only slight modifications of the gland accompany
      further development to the end of metamorphosis. Development of the thyroid gland
      involves degeneration, proliferation, and reorganization of the cells in the
      endostyle, and changes in their fine structure. Ultrastructural changes during
      early stages are most obvious in the type 1 cells that make up the shrinking
      glandular tracts, and involves the accumulation of cytoplasmic microfilaments and
      a variety of cytoplasmic inclusions. The glandular tracts and their cells
      gradually disappear through autolysis and, apparently, through phagocytosis by
      neighboring epithelial cells and macrophages. Although the fine structure of the
      type 2, 3, 4, and 5 cells is not altered in the early stages, by stage 3, many of
      these cells become either vacuolated, undergo autolysis, or are extruded.
      Phagocytosis of some of each of these cell types likely occurs. Thyroid follicles
      are first observed during stage 4. Some of their lumina seem to arise from the
      accumulation of material in intercellular spaces and from vacuoles among cell
      clusters. Other lumina may represent a portion of the original lumen of the
      endostyle. Many follicles appear to be comprised of cells with cytological
      characteristics similar to those of larval cell types 3 and 2c. Some of the other
      larval cell types, such as type 5, may also be involved. In young adult lampreys
      follicles are composed of cuboidal to columnar cells that lack the dilated
      cisternae of rough endoplasmic reticulum seen in follicular cells of higher
      vertebrates. Dense collagenous connective tissue surrounding the follicles
      contains relatively few blood vessels. The transformation process described may
      have some relevance to our understanding of the development and evolution of the
      vertebrate thyroid gland.

PMID- 30189712
TI  - Ultrastructural study of two kinds of muscle in sea anemones: The existence of
      fast and slow muscles.
AB  - The sea anemones studied have two morphological types of muscle fiber. Types A
      and B are distinguishable on the basis of myofilament patterns, size of fibers,
      responses to fixation, and staining with methylene blue. Observation of the
      muscle in both resting and contracted states has shown that the two types do not
      result from differences in contraction state of the muscle. The fine structural
      characteristics distinguishing A and B fibers are similar to those which
      distinguish fast and slow muscle fibers in higher animals. The distribution of A
      and B fibers in Stomphia and Aiptasia is consistent with the distribution of fast
      and slow muscles in these two species. It is proposed that the A and B fibers
      represent two morphologically distinct kinds of smooth muscle, and that the
      capacity for fast and slow contraction in the muscles of Stomphia and Aiptasia,
      and possibly in all actinians, is due to morphological differentiation in the
      muscle system.

PMID- 30189714
TI  - Avian scale development. VI. Ultrastructure of the keratinizing cells of
      reticulate scales.
AB  - Reticulate scales develop as radial symmetrical anlagen, in contrast to scuttate
      scales which appear initially as "epidermal placodes." Unlike scuttate scales
      whose outer and inner epidermal surfaces elaborate beta-and alpha-type keratins,
      respectively, reticulate scales elaborate only one type of epidermal surface
      which has been reported to give an alpha-type, X-ray diffraction pattern. We find
      that, histologically and ultrastructurally, this surface differs from either
      epidermal surface of scuttate scales. The keratinizing cells become filled with
      long interweaving bundles of alpha-filaments which aggregate into rather
      homogeneous alpha-fibrils. Keratohyalin granules, which have been shown to be
      associated with other keratinizing regions in the bird, do not form during the
      keratinization of reticulate scale epidermis.

PMID- 30189713
TI  - Ultrastructure of siliceous spicules and microsclerocytes in the marine sponge
      Neofibularia irata N. SP.
AB  - The marine sponge Neofibularia irata contains four different categories of
      siliceous spicules. These spicules are evident in the tissues as distinct bundles
      that act to increase the structural rigidity of the sponge. All spicules have a
      normal structural morphology with silica deposition around a hexagonal axial
      canal containing a crystalline axial filament. The megasclere strongyles are
      secreted in typical megasclerocytes. The sigma and raphid microscleres are
      secreted in individual microsclerocytes that are grouped together in parallel to
      form loose bundles. However, the microxea microscleres are apparently secreted in
      distinct tight bundles (trichodragmas) within a single cell. These cells,
      containing between 13 and 39 spicules, are grouped to form large packets of
      bundles of spicules.

PMID- 30189715
TI  - Ultrastructure of the tastebuds of the red-eared turtle, Chrysemys scripta
      elegans.
AB  - The fine structure of the turtle tastebud has been examined by light,
      transmission, and scanning electron microscopy. It contains five types of cells
      on the basis of their cytological features, designated types 1,2,3,A, and B.
      Types 1, 2, and 3 reach the taste pore, whereas types A and B are located
      basally. The type 2 cell has access to the tongue surface, i.e., the site of
      gustatory stimuli, and also synapses onto afferent nerves; it probably is a
      gustatory receptor cell and corresponds to the so-called "light" cell observed in
      other vertebrate tastebuds. Some cells may be differentiating. In support of this
      hypothesis, light microscopic autoradiography shows that postmitotic cells occur
      in the tastebuds within 24 hours after administration of H3 -thymidine. The
      tastebuds of the turtle are similar to those of other vertebrates described
      electron-microscopically.

PMID- 30189716
TI  - Exercise training in patients with chronic heart failure: A new challenge for
      Cardiac Rehabilitation Community.
AB  - Exercise training (ET) is strongly recommended in patients with chronic stable
      heart failure (HF). Moderate-intensity aerobic continuous ET is the best
      established training modality in HF patients. In the last decade, however, high
      intensity interval exercise training (HIIT) has aroused considerable interest in
      cardiac rehabilitation community. In HF patients, HIIT exerts larger improvements
      in exercise  capacity compared to moderate-continuous ET. Since better functional
      capacity translates into symptoms relief and improvement in quality of life in
      patients with HF, this training modality is collecting growing interest and
      consensus, not revealing major safety issues. HIIT should not replace other
      training modalities in HF but should rather complement them. Inspiratory muscle
      training, another promising training modality in patients with HF, exerts
      beneficial effect on inspiratory muscle strength and inspiratory endurance, on
      exercise capacity and quality of life. In conclusion, taking into consideration
      the complecity of HF syndrome, combining and tailoring different ET modalities
      according to each patient's baseline clinical characteristics (i.e. exercise
      capacity, comorbidity, frailty status, personal needs, preferences and goals)
      seem the most wily approach for exercise prescription.

PMID- 30189717
TI  - Is Hyperbaric Oxygen Therapy Effective in Cisplatin-Induced Ototoxicity in Rats?
AB  - Objectives: Cisplatin is an antineoplastic agent, used in the treatment of
      different types of malignant neoplasms. Side effects such as ototoxicity,
      nephrotoxicity, and bone marrow toxicity are the main limitations of its clinical
      use. The aim of the present study was to evaluate the possible effects of
      hyperbaric oxygen (HBO) therapy as a protective agent in cisplatin-induced
      ototoxicity in rats. Methods: A total of 30 adult Wistar rats (60 ears) were
      divided into five equal groups. Group 1 is a control group; group 2 is HBO
      therapy group; group 3 received 15 mg/kg cisplatin intraperitoneally; group 4
      received 15 mg/kg cisplatin intraperitoneally and HBO treatment on the same day;
      group 5 received 15 mg/kg cisplatin intraperitoneally and HBO treatment 72 hours
      later. The effect of ototoxicity was measured with distortion product otoacoustic
      emission testing performed on the days 1, 3, and 7. Results: Groups 4 and 5 that
      received HBO treatment after cisplatin had better signal-to-noise ratio (SNR)
      values compared with group 3 that received only cisplatin (P<0.05). Compared with
      group 5, group 4 (same day HBO treatment) had better SNR values (P<0.05).
      Conclusion: HBO was found effective for prevention of cisplatin-induced
      ototoxicity in rats. Our study differs from other studies regarding using a
      promising treatment, which does not expose subjects to extra stress.

PMID- 30189718
TI  - Prediction of Obstructive Sleep Apnea Based on Respiratory Sounds Recorded
      Between Sleep Onset and Sleep Offset.
AB  - Objectives: To develop a simple algorithm for prescreening of obstructive sleep
      apnea (OSA) on the basis of respiratory sounds recorded during polysomnography
      during all sleep stages between sleep onset and offset. Methods: Patients who
      underwent attended, in-laboratory, full-night polysomnography were included. For
      all patients, audio recordings were performed with an air-conduction microphone
      during polysomnography. Analyses included all sleep stages (i.e., N1, N2, N3,
      rapid eye movement, and waking). After noise reduction preprocessing, data were
      segmented into 5-s windows and sound features were extracted. Prediction models
      were established and validated with 10-fold cross-validation by using simple
      logistic regression. Binary classifications were separately conducted for three
      different threshold criteria at apnea hypopnea index (AHI) of 5, 15, or 30.
      Prediction model characteristics, including accuracy, sensitivity, specificity,
      positive predictive value (precision), negative predictive value, and area under
      the curve (AUC) of the receiver operating characteristic were computed. Results:
      A total of 116 subjects were included; their mean age, body mass index, and AHI
      were 50.4 years, 25.5 kg/m2 , and 23.0/hr, respectively. A total of 508 sound
      features were extracted from respiratory sounds recorded throughout sleep.
      Accuracies of binary classifiers at AHIs of 5, 15, and 30 were 82.7%, 84.4%, and
      85.3%, respectively. Prediction performances for the classifiers at AHIs of 5,
      15, and 30 were AUC, 0.83, 0.901, and 0.91; sensitivity, 87.5%, 81.6%, and 60%;
      and specificity, 67.8%, 87.5%, and 94.1%. Respective precision values of the
      classifiers were 89.5%, 87.5%, and 78.2% for AHIs of 5, 15, and 30. Conclusion:
      This study showed that our binary classifier predicted patients with AHI of >=15
      with sensitivity and specificity of >80% by using respiratory sounds during
      sleep. Since our prediction model included all sleep stage data, algorithms based
      on respiratory sounds may have a high value for prescreening OSA with mobile
      devices.

PMID- 30189719
TI  - A Phase II Trial of Osimertinib in the Second-Line Treatment of Non-small Cell
      Lung Cancer with the EGFR T790M Mutation, Detected from Circulating Tumor DNA:
      LiquidLung-O-Cohort 2.
AB  - Purpose: Administering the best treatment after failure of epidermal growth
      factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy requires knowledge
      of resistance status. In this trial, treatment efficacy of osimertinib was
      assessed in patients with non-small cell lung carcinoma (NSCLC) harboring the
      T790M resistance mutation, detected from circulating tumor DNA (ctDNA) with
      unknown tumor mutation status. Materials and Methods: To extract ctDNA from
      plasma, 15 mL of peripheral blood was withdrawn and centrifuged immediately
      before storage. CobasTM version 2 and PANA MutyperTM were used for ctDNA
      genotyping. Patients with T790M, detected from ctDNA, were enrolled and they
      received a once-daily administration of osimertinib, 80 mg. The primary endpoint
      was objective response rate (ORR), and secondary endpoints were ctDNA test
      sensitivity, progression-free survival (PFS), duration of response (DoR), and
      safety (ClinicalTrials.gov, Identifier: NCT02769286). Results: Eighty patients
      with acquired resistance to prior EGFR-TKI therapies were screened. ctDNA of 21
      patients showed T790M positivity, and 19 patients were enrolled. In the response
      evaluable population (n=15), ORR was 66.7% (10/15). Median PFS was 8.3 months
      (95% confidence interval [CI], 7.9-8.7) and median DoR was 6.8 months (95% CI,
      5.3-8.3) in the intent-to-treat population (n=19). No subject experienced drug
      related adverse event of grades >=3 or required dose reduction. The sensitivity
      of the ctDNA tests was 56.8% using both methods and 45.9% with either method from
      the estimated T790M-positive cases. Conclusion: Osimertinib has favorable
      efficacy in patients with NSCLC harboring T790M, detected from ctDNA with unknown
      tumor mutation status, in whom disease had progressed during prior EGFR-TKI
      therapy.

PMID- 30189720
TI  - Application of the International Metastatic Renal Cell Carcinoma Database
      Consortium and Memorial Sloan Kettering Cancer Center Risk Models in Patients
      with Metastatic Non-Clear Cell Renal Cell Carcinoma: A Multi-Institutional
      Retrospective Study Using the Korean Metastatic Renal Cell Carcinoma Registry.
AB  - Purpose: The International Metastatic Renal Cell Carcinoma Database Consortium
      (IMDC) and the Memorial Sloan Kettering Cancer Center (MSKCC) risk models were
      developed predominantly with clear cell renal cell carcinoma. Accordingly,
      whether these two models could be applied to metastatic non-clear cell RCC
      (mNCCRCC) as well has not been well-known and was investigated herein. Materials
      and Methods: From the Korean metastatic RCC registry, a total of 156 patients
      (8.1%) with mNCCRCC among the entire cohort of 1,922 patients were analyzed. Both
      models were applied to predict first-line progression-free survival (PFS), total
      PFS, and cancer-specific survival (CSS). Results: The median first-line PFS,
      total PFS, and CSS were 5, 6, and 24 months, respectively. The IMDC risk model
      reliably discriminated three risk groups to predict survival: The median first
      line PFS, total PFS, and CSS for the favorable, intermediate, and poor risk
      groups were 9, 5, and, 2 months (p = 0.0014); 14, 7, and 2 months (p=0.0002); and
      41, 21, and 8 months (p<0.0001), all respectively. The MSKCC risk model also
      reliably differentiated three risk groups: 9, 5, and, 2 months (p=0.0047); 10, 7,
      and 3 months (p=0.0023); and 50, 21, and 8 months (p<0.0001), also all
      respectively. The concordance indices were 0.632 with the IMDC model and 0.643
      with the MSKCC model for first-line PFS: 0.748 and 0.655 for CSS. Conclusion: The
      current IMDC and MSKCC risk models reliably predict first-line PFS, total PFS,
      and CSS in mNCCRCC.

PMID- 30189721
TI  - Genome-Wide Association of Genetic Variation in the PSCA Gene with Gastric Cancer
      Susceptibility in a Korean Population.
AB  - Purpose: Half of the world's gastric cancer cases and the highest gastric cancer
      mortality rates are observed in Eastern Asia. Although several genome-wide
      association studies (GWASs) have revealed susceptibility genes associated with
      gastric cancer, no GWASs have been conducted in the Korean population, which has
      the highest incidence of gastric cancer. Materials and Methods: We performed
      genome scanning of 450 gastric cancer cases and 1,134 controls via Affymetrix
      Axiom Exome 319 arrays, followed by replication of 803 gastric cancer cases and
      3,693 healthy controls. Results: We showed that the rs2976394 in the prostate
      stem cell antigen (PSCA) gene is a gastric-cancer-susceptibility gene in a Korean
      population, with genome-wide significance and an odds ratio (OR) of 0.70 (95%
      confidence interval [CI]=0.64-0.77). A strong linkage disequilibrium with
      rs2294008 was also found, indicating an association with susceptibility.
      Individuals with the CC genotype of the PSCA gene showed an approximately 2-fold
      lower risk of gastric cancer compared to those with the TT genotype (OR=0.47; 95%
      CI=0.39-0.57). The effect of the PSCA gene on gastric cancer was more prominent
      in the female population and for diffuse type gastric cancer. Conclusion: Our
      result confirmed that the PSCA gene may be the most important susceptibility gene
      for gastric cancer risk in a Korean population.

PMID- 30189722
TI  - Discordance of the PAM50 Intrinsic Subtypes Compared with IHC-Based Surrogate in
      Breast Cancer Patients: Potential Implication of Genomic Alterations of
      Discordance.
AB  - Purpose: We aimed to analyze the discordance between immunohistochemistry (IHC)
      based surrogate subtyping and PAM50 intrinsic subtypes and to assess overall
      survival (OS) according to discordance. Materials and Methods: A total of 607
      patients were analyzed. Hormone receptor (HR) expression was evaluated by IHC,
      and human epidermal growth factor receptor 2 (HER2) expression was analyzed by
      IHC and/or fluorescence in situ hybridization. PAM50 intrinsic subtypes were
      determined according to 50 cancer genes using the NanoString nCounter Analysis
      System. We matched concordant tumor as luminal A and HR+/HER2-, luminal B and
      HR+/HER2+, HR-/HER2+ and Her2-enriched, and triple-negative breast cancer and
      normal- or basal-like. We used Ion Ampliseq Cancer Panel v2 was used to identify
      the genomic alteration related with discordance. The Kaplan-Meier method was used
      to estimate OS. Results: In total, 233 patients (38.4%) were discordant between
      IHC-based subtype and PAM50 intrinsic subtype. Using targeted sequencing, we
      detected somatic mutation-related discordant breast cancer including the VHL gene
      in the HR+/HER2- group (31% in concordant group, 0% in discordant group, p=0.03)
      and the IDH and RET genes (7% vs. 12%, p=0.02, 0% vs. 25%, p=0.02, respectively)
      in the TNBC group. Among the luminal A/B patients with a discordant result had
      significantly worse OS (median OS, 73.6 months vs. not reached, P<0.001), and
      among the patients with HR positivity, the basal-like group as determined by
      PAM50 showed significantly inferior OS compared to other intrinsic subtypes (5
      year OS rate, 92.2% vs. 75.6%, P=0.01). Conclusion: A substantial portion of
      patients showed discrepancy between IHC subtype and PAM50 intrinsic subtype in
      our study. The survival analysis demonstrated that current IHC-based
      classification could mislead the treatment and result in poor outcome. Current
      guidelines for IHC might be updated accordingly.

PMID- 30189723
TI  - Prophylactic efficacy of probiotics on travelers' diarrhea: an adaptive meta
      analysis of randomized controlled trials.
AB  - OBJECTIVES: The 2017 guideline for the prevention of travelers' diarrhea (TD) by
      the International Society of Travel Medicine suggested that 'there is
      insufficient evidence to recommend the use of commercially available prebiotics
      or probiotics to prevent or treat TD.' However, a meta-analysis published in 2007
      reported significant efficacy of probiotics in the prevention of TD (summary
      relative risk [sRR], 0.85, 95% confidence interval [CI], 0.79 to 0.91). This
      study aimed to synthesize the efficacy of probiotics on TD by updating the meta
      analysis of double-blind, placebo-controlled, randomized human trials. METHODS:
      The search process was conducted by the adaptive meta-analysis method using the
      'cited by' and 'similar articles' options provided by PubMed. The inclusion
      criteria were double-blind, placebo-controlled, randomized human trials with
      hypotheses of probiotics as intervention and TD as an outcome. The adaptive meta
      analysis was conducted using Stata software using the csi, metan, metafunnel, and
      metabias options. RESULTS: Eleven articles were selected for the meta-analysis.
      The sRR was 0.85 (95% CI, 0.79 to 0.91) and showed statistical significance.
      There was no heterogeneity (I-squared=28.4%) and no publication bias.
      CONCLUSIONS: Probiotics showed statistically significant efficacy in the
      prevention of TD.

PMID- 30189724
TI  - Fluorescent Imaging of beta-Amyloid Using BODIPY Based Near-Infrared Off-On
      Fluorescent Probe.
AB  - Fluorescent imaging of beta-amyloid (Abeta) is one of the most promising methods
      for Alzheimer's disease diagnosis. Several fluorescent probes have been reported
      to detect Abeta both in vitro and in vivo. However, highly sensitive and highly
      selective probes with low background signals are still greatly needed. Herein, we
      rationally designed and synthesized a PIET quenched near-infrared probe QAD-1 to
      detect Abeta. This probe contains BODIPY as fluorophore and tetrahydroquinoxaline
      as the quenching group. QAD-1 exhibited significant fluorescent switch-on after
      binding to soluble and insoluble Abeta species, and the probe had the benefit of
      low background signal to stain Abeta plaques without the need of wash-out
      procedures in vitro, which was specially found by the fluorescence off-on probe.
      QAD-1 could identify the overproduced Abeta in transgenic (APPSWE/PSEN 1dE9) AD
      mice as early as 6 months old in vivo, which indicated that QAD-1 may be a
      potential probe for monitoring Abeta species at an early stage of AD.

PMID- 30189725
TI  - Mechanisms of CO2 Incorporation into Propargylic Amine Catalyzed by Ag(I)/Amine
      Catalysts.
AB  - Density functional theory calculations are carried out to explore the detail
      mechanisms of CO2 incorporation into propargylic amine catalyzed by Ag(I)/amine
      catalysts. Our calculations reveal that the whole reaction involves Lewis acid
      catalysis and Lewis base catalysis stages, and the outcomes of this reaction
      critically depend on the basicity of amine. A weaker base (i.e., DABCO) makes the
      Ag center more acidic, thus favoring the Lewis acid catalysis, resulting in
      benzoxazin-2-one. However, the following rearrangement of benzoxazin-2-one
      requires a stronger base (i.e., DBU) to stabilize its deprotonated form. Thus,
      the product selectivity could be subtly tuned by the choice of amine and the
      condition control, consistent with the experimental observations.

PMID- 30189726
TI  - Efficient Photochemical Vapor Generation of Molybdenum for ICPMS Detection.
AB  - Photochemical vapor generation (PVG) of Mo was accomplished using a 19 W high
      efficiency flow-through photoreactor operating in a flow injection mode using 30
      50% (w/v) formic acid as a reaction medium. The generated volatile product (most
      probably molybdenum hexacarbonyl) was directed by an argon carrier gas to a
      plastic gas-liquid separator and introduced into the spray chamber of an
      inductively coupled plasma mass spectrometer for detection. Particular attention
      was paid to the determination of overall PVG efficiency relative to that for
      liquid nebulization. Utilizing a sample flow rate of 1.25 mL min-1, corresponding
      to an irradiation time of 38 s, PVG efficiencies in the range 46-66% were
      achieved. The efficiency could be further enhanced by the presence of mg L-1
      added Fe3+ ions. A limit of detection of 1.2 ng L-1 and precision of 3% (RSD) at
      250 ng L-1 were achieved. Interferences from inorganic anions likely to be
      encountered during analytical application to real samples (NO3-, Cl-, SO42-, NO2
      , and ClO4-) were investigated in detail. The accuracy and applicability of this
      sensitive methodology was successfully verified by analysis of fresh water
      Standard Reference Material NIST 1643e, two seawater Certified Reference
      Materials (NASS-7 and CASS-6), and by analysis of two samples of commercial
      dietary supplements solubilized in formic acid.

PMID- 30189727
TI  - Cell Surface-Anchored DNA Nanomachine for Dynamically Tunable Sensing and Imaging
      of Extracellular pH.
AB  - DNA nanodevices that mimic natural biomolecular machines changing configurations
      in response to external inputs have enabled smart sensors to live cell imaging.
      We report for the first time the development of a dynamic DNA nanomachine that is
      anchored on a cell's surface and undergoes pH-responsive triplex-duplex
      conformation switching, allowing tunable sensing and imaging of extracellular pH.
      Results reveal that the DNA nanomachine can be stably anchored on the cell
      surface via multiple anchors, and the adjustment of C+G-C content in the switch
      element confers tunability of pH response windows. The anchored DNA nanomachine
      also demonstrates desirable sensitivity, excellent reversibility, and
      quantitative ability for extracellular pH detection and imaging. This cell
      surface-anchored pH-responsive DNA nanomachine can provide a useful platform for
      pH sensing in extracellular microenvironments and diagnostics of different pH
      related diseases.

PMID- 30189729
TI  - Effect of Indole-3-Carbinol on Dimyristoylphosphatidylcholine Multilamellar
      Vesicles.
AB  - This study reports the interaction of indole-3-carbinol (I3C), which is a
      chemopreventive reagent, with an artificial model membrane
      {(dimyristoylphosphatidylcholine (DMPC) multilamellar vesicles (MLVs)}, using the
      intrinsic fluorescence properties of I3C, extrinsic fluorescence properties of
      Nile Red (NR), differential scanning calorimetry (DSC), dynamic light scattering
      (DLS), and confocal microscopy. The intrinsic fluorescence of I3C helps to
      provide information about its location, partitioning ability, and sensitivity
      toward the phase-transition temperature of liposomes, confirmed by
      cetylpyridinium chloride (CPC) quenching study, partition coefficient values
      {(4.60 +/- 0.1) * 105 (solid gel phase) and (7.29 +/- 0.1) * 105 M-1 (liquid
      crystalline phase)} and temperature-dependent emission behavior of I3C. I3C
      perturbs the DMPC MLVs above 15 mol %, as observed using the fluorescence
      properties of NR, DSC, and DLS data. This perturbation occurs as a consequence of
      interfacial hydration of the DMPC MLVs, which was clearly indicated by the
      fluorescence properties (emission intensity, fluorescence lifetime, and
      nonextensive distribution analysis) of NR.

PMID- 30189728
TI  - Enzyme Pretreatment Enhancing Biogas Yield from Corn Stover: Feasibility,
      Optimization, and Mechanism Analysis.
AB  - In this study, feasibility, optimization, and mechanisms of enzyme pretreatment
      to enhance anaerobic digestion of corn stover were investigated. Results showed
      that the enzyme pretreatment efficiently enhanced the biogas yield, and the
      optimal conditions of enzyme pretreatment were an enzyme load of 30 FPU/g, a
      pretreatment time of 24 h, and a solid content of 60 g/L. Under the optimal
      conditions, the cumulative biogas yield increased by 36.9%, which was mainly
      attributed to disruption of surface structure and degradation of noncrystalline
      cellulose in the enzyme-pretreated corn stover. The kinetic analysis indicated
      that enzyme pretreatment significantly enhanced the hydrolysis rate and biogas
      production rate to 0.15/d and 23.89 mL/gVS, and shortened the lag phase time to
      1.2 d. Correlation analysis illustrated that the SCOD yield of 250-350 mg/g from
      corn stover after enzyme pretreatment was suitable for the further anaerobic
      digestion of corn stover.

PMID- 30189730
TI  - Fe(II)-Catalyzed Transformation of Organic Matter-Ferrihydrite Coprecipitates: A
      Closer Look Using Fe Isotopes.
AB  - Ferrihydrite is a common Fe mineral in soils and sediments that rapidly
      transforms to secondary minerals in the presence of Fe(II). Both the rate and
      products of Fe(II)-catalyzed ferrihydrite transformation have been shown to be
      significantly influenced by natural organic matter (NOM). Here, we used enriched
      Fe isotope experiments and 57Fe Mossbauer spectroscopy to track the formation of
      secondary minerals, as well as electron transfer and Fe mixing between aqueous
      Fe(II) and ferrihydrite coprecipitated with several types of NOM. Ferrihydrite
      coprecipitated with humic acids transformed primarily to goethite after reaction
      with Fe(II). In contrast, ferrihydrite coprecipitated with fulvic acids and
      Suwannee River NOM (SRNOM) resulted in no measurable formation of secondary
      minerals. Despite no secondary mineral transformation, Mossbauer spectra
      indicated electron transfer still occurred between Fe(II) and ferrihydrite
      coprecipitated with fulvic acid and SRNOM. In addition, isotope tracer
      experiments revealed that a significant fraction of structural Fe in the
      ferrihydrite mixed with the aqueous phase Fe(II) (~85%). After reaction with
      Fe(II), Mossbauer spectroscopy indicated some subtle changes in the
      crystallinity, particle size, or particle interactions in the coprecipitate. Our
      observations suggest that ferrihydrite coprecipitated with fulvic acid and SRNOM
      remains a highly dynamic phase even without ferrihydrite transformation.

PMID- 30189731
TI  - Mechanisms of Transformation of Bulk Aluminum-Lithium Alloys to Aluminum Metal
      Organic Nanowires.
AB  - Fabrication and applications of lightweight, high load-bearing, thermally stable
      composite materials would benefit greatly from leveraging the high mechanical
      strength of ceramic nanowires (NWs) over conventional particles or micrometer
      scale fibers. However, conventional synthesis routes to produce NWs are rather
      expensive. Recently we discovered a novel method to directly convert certain bulk
      bimetallic alloys to metal-organic NWs at ambient temperature and pressure. This
      method was demonstrated by a facile transformation of polycrystalline aluminum
      lithium (AlLi) alloy particles to aluminum alkoxide NWs, which can be further
      transformed to mechanically robust aluminum oxide (Al2O3) NWs. However, the
      transformation mechanisms have not been clearly understood. Here, we conducted
      advanced materials characterization (via electron microscopy and nuclear magnetic
      resonance spectroscopies) and chemo-mechanical modeling to elucidate key physical
      and chemical mechanisms responsible for NWs formation. We further demonstrated
      that the content of Li metal in the AlLi alloy could be reduced to about 4 wt %
      without compromising the success of the NWs synthesis. This new mechanistic
      understanding may open new avenues for large-scale, low-cost manufacturing of NWs
      and nanofibers for a broad range of composites and flexible ceramic membranes.

PMID- 30189732
TI  - Quantifying Asymmetry of Multimeric Proteins.
AB  - A large number of proteins assemble as homooligomers. These homooligomers
      accomplish their function either symmetrically or asymmetrically. If asymmetry is
      prevalent in a structure ensemble, the asymmetric motion will occur in any of the
      subunits. Many computational analysis tools implicitly use ensemble averages to
      determine protein motions, e.g., principle component analysis. Therefore, taken
      together, this approach results in a loss of the asymmetric signal and a false
      symmetric output, rendering it impossible to analyze asymmetric motions with
      available tools. A first step toward understanding asymmetric systems is the
      quantification of asymmetry. Only a few tools exist to calculate asymmetry
      quantitatively, such as the continuous symmetry measure (CSM). In this study, we
      present an extension of CSM delivering additional information about the subunit
      contributions to the overall asymmetry. Furthermore, we introduce an algorithm
      termed the functional asymmetry measure (FAME). FAME is based on an algorithm
      that predicts functionally relevant motions of a protein (PLS-FMA) and thus
      allows calculating asymmetry in relation to protein function. To validate our
      developed algorithm, we applied it to two different potassium channels, TREK-2
      and KcsA, as well as to the unfolding mechanism of the carrier protein
      Transthyretin. For both potassium channel systems, an artificial asymmetric
      motion was introduced to benchmark the algorithm in addition to demonstrate the
      interpretation potential of the results. Therefore, the degree of overall as well
      as subunit based asymmetry for KcsA was quantified using CSM as the provided
      extension requires more than two subunits. The functional modes of asymmetric
      TREK-2 motions were recovered and their asymmetry was quantified using FAME as a
      dimeric protein is the simplest application. FAME was further used to study the
      asymmetry of the unfolding pathway of Transthyretin. We show the ability of both
      algorithms to correctly predict asymmetry. The tools are available online and can
      be applied to most homooligomeric systems.

PMID- 30189733
TI  - Melatonin as a structural template in the development of novel drugs for
      neurodegenerative disorders.
AB  - Melatonin is a key regulatory hormone produced mainly in the pineal gland. In the
      recent years, melatonin contribution to neurodegenerative disorders has
      dramatically increased when inspecting its favorable pharmacological profile. Its
      levels were found to be decreased during aging. Data from clinical studies point
      out to its positive outcome not only in improving the quality of sleep but it
      also exerts anti-inflammatory and antioxidant profile. Moreover, it was found as
      an effective neuroprotective agent. Current study summarizes the experimental
      data from basic research of medicinal chemistry field devoted to melatonin.
      Particular emphasis is directed toward melatonin derivatives with multipotent
      profile affecting concomitantly several pathological hallmarks of the
      neurodegenerative disorders. Key words: acetylcholinesterase * Alzheimer's
      disease * antioxidant * butyrylcholinesterase * melatonin * neurodegenerative
      disorders.

PMID- 30189734
TI  - Superdisintegrants used in pharmaceutical technology.
AB  - Disintegrants are substances which promote disintegration of the solid dosage
      form in the dissolution medium or body fluids. Efficient disintegration is an
      important prerequisite for ensuring release of the active substance and its good
      bioavailability. Several mechanisms of disintegrants' action are currently
      recognized, but disintegration is a complex process, and the majority of
      substances act by combining multiple mechanisms. Superdisintegrants as an
      innovative materials allow more efficient disintegration of the dosage form in
      lower concentrations, without any negative impact on processability and
      mechanical properties of the final dosage form. Currently are in pharmaceutical
      technology used synthetic, modified (semi-synthetic), and also natural
      superdisintegrants, whose main representatives discribes this article. Key words:
      disintegrants * superdisintegrants * solid dosage forms * tablets *
      disintegration time * excipients.

PMID- 30189735
TI  - Selenium in the prevention and subsidiary therapy of cancer of soft tissues.
AB  - Selenium as an antioxidant has attracted attention because of its anticancer
      activity. This review presents a view on selenium and its compounds exerting
      influence against cancer in the soft tissues. The results reveal a significant
      strong association between a low selenium level in blood and a cancer risk.
      Seleno-supplementation is important in the prevention of metastatic cancer. These
      results help to elucidate the anticancer effect of selenium providing further
      evidence to exploit novel anticancer agents targeting selenium-containing organic
      compounds. Key words: selenium * cancer prevention * cancer treatment * soft
      tissues.

PMID- 30189736
TI  - Microbiome in connection with metabolic syndrome and the therapeutic potential of
      its influencing.
AB  - Several fields of medicine have been concerned with the role of the microbiome in
      maintaining the balance in the human body and its changes in the pathogenesis of
      diseases in recent years. The intestinal microbiome seems to play a key role in
      the regulation of metabolic pathways, inflammation and intestinal permeability.
      The aim of this review is to assess the importance of the intestinal microbiome
      in metabolic syndrome and the therapeutic or preventive potential of its
      manipulation. Key words: metabolic syndrome * microbiome * probiotics *
      prebiotics * fecal transplant.

PMID- 30189737
TI  - On the content of the National part of the Czech Pharmacopoeia 2017.
AB  - This paper deals with the content of the national part of the Czech Pharmacopoeia
      (CP) 2017 in terms of preparation of pharmaceuticals in pharmacies, quantitative
      methods for controlling their quality and their usable life. Despite the longer
      time span of the CP 2017 since the CP 2009, compared to the CP 2009 from the CP
      2005, the content of the CP 2017 can not be evaluated as a more pronounced shift
      from the national part of the CP 2009. Some issues of the national section of the
      CP 2017 are discussed in detail in the paper. Key words: Czech Pharmacopoeia 2017
      * content of the national part * preparation of medicinal products in pharmacies.

PMID- 30189738
TI  - Enchiridion medicinae by Georg Henisch (1549-1618).
AB  - Georg Henisch (1549-1618), a native of Bardejov, for all of his life as a teacher
      at St. Anne's Grammar School in Augsburg, Germany. He was a very prolific
      polyhistor, publishing spiritual and occasional poetry, works on medicine,
      mathematics, rhetoric, dialectics, astronomy, linguistics and geography, editions
      of some ancient authors, and several translations. In 1573 he issued the
      pharmaceutical guide Enchiridion medicinae, which presents medications and
      remedies for individual health problems without any further comment on their
      effects and usage. However, this guide had a precursor, published in Paris in
      1571, but with no mention of the author, and it is not certain that Henisch
      produced it. The text is de facto identical, there are only minimal variations,
      but the second edition has a longer title, it is extended with an introduction
      and the final part containing some prescriptions. In 1571, when the first edition
      was issued, Henisch was just 22-years old, and in 1573 he was still only 24, so
      in his case life experience cannot be taken into account. Comparison of the work
      with contemporary medical literature has shown that Enchiridion medicinae is not
      an original work, but a compilation of three works by other authors: De materia
      medicinali et compositione medicorum by G. Rondelet from 1556, a commentary to
      Galen's Quos, quibus quando purgare oporteat by the French author Sebastien
      Coquilitus Scipio from 1553, and the book Lilium medicinae by Bernard de Gordon
      from 1550. Key words: Georg Henisch * pharmacy in the 16th century *
      pharmaceutical handbook Enchiridion medicinae.

PMID- 30189739
TI  - Hybrid imaging PET/MR in prostatic carcinoma.
AB  - Imaging of the own prostatic tissue is being not easy using standard tumour
      imaging approaches, contrast enhanced computed tomography and the hybrid imaging
      using PET/CT with the application of the 18F-fluorodeoxyglucose. Magnetic
      resonance imaging is useful in detection of the patients with the elevated
      prostatic specific antigen (PSA) and/or with the increased index of the health
      prostate index (PHI). The novel imaging possibilities of the imaging is hybrid
      positron emission tomography - magnetic resonance imaging (PET/MR) with the
      application of 18F-fluorocholine (FCH), 18F-natriumfluoride (18F-NaF) or 68Ga
      PSMA-11 (ligand of prostatic specific membrane antigen) in detection, staging or
      restaging of the prostatic carcinoma. PET/MR represents current optimal method of
      the staging, restaging and therapy response evaluation of prostatic carcinoma.>
      Keywords: prostatic carcinoma, PET/MR, 18F-fluorocholine, 18F-natriumfluoride,
      68Ga-PSMA-11.

PMID- 30189740
TI  - Contrast-enhanced ultrasonography.
AB  - Review summarizes state of the art of contrast-enhanced ultrasonography (CEUS),
      pinpoints technical basics and also economical comparison with other imaging
      methods. Most often indications of CEUS in different anatomical regions with
      differential diagnosis are discussed.

PMID- 30189741
TI  - Coronary CT angiography - current options and future perspectives in the
      diagnosis of coronary artery disease.
AB  - Computed tomography (CT) is currently an imaging method with a very wide use in
      acute and chronic diagnostics. Technological development of the method has
      gradually enabled a good view of the coronary flow in a noninvasive way. The
      article summarizes the current possibilities of coronary CT angiography, a proven
      method for the detection of coronary atherosclerosis. Its main advantage is
      particularly a simplicity and a design safety and potentially a high
      availability. An ever-increasing number of clinical trials has been validating
      the possible relevance of CT angiography in a variety of clinical situations and
      it is highly probable to expect a widening of the spectrum of indications,
      particularly in a group of patients with a higher pretest probability of coronary
      artery disease. At the same time, it can be expected to be an essential method in
      acute diagnosis with the necessity of its permanent availability in acute care.
      The above-mentioned facts will lead to the need for targeted coordination of
      performing radiological workplaces, particularly in complex cardiovascular
      centers, to ensure the quality and availability of the method with respect to the
      probable increase in the number of method's indications.

PMID- 30189742
TI  - Endovascular recanalization and fast diagnosis improve results of ischemic stroke
      therapy.
AB  - The benefit of mechanical thrombectomy over intravenous thrombolysis was
      definitively proved by several studies in 2015. It is relevant for proximal,
      large artery occlusions in the anterior circulation with onset of clinical
      symptoms lasting 6 hours. Two trials published in 2018 showed that in patients
      who are selected using CT perfusion or MR diffusion weighted imaging,
      thrombectomy significantly improves outcome even up to 24 hours from onset. The
      benefit of the vertebrobasilar circulation, where occlusion of large arteries
      occurs in 7 % cases, has not been proved by randomised studies yet. However,
      mechanical thrombectomy is performed in this arterial territory because of very
      poor prognosis of nonrecanalized occlusions there. Patients with acute ischemic
      stroke should be transferred to comprehensive stroke centres. These centres
      should provide parenchymal CT imaging and CT arteriography. These two modalities
      provide sufficient information to determine eligibility for endovascular
      treatment in the first 6 hours from stroke onset. Physicians performing
      endovascular therapy of stroke must be properly trained in clinical neuroscience,
      neuroimaging and neurointerventions. Success rate of this therapy depends on its
      organization which includes fast transport of patients, fast clinical and
      diagnostic evaluation, fast decisions, and availability of trained interventional
      team.

PMID- 30189744
TI  - Vertebroplasty and epiduroscopy as seen by interventional radiologist.
AB  - Two minimally-invasive techniques in the spinal region are introduced:
      vertebroplasty and epiduroscopy. Vertebroplasty is mostly used in the treatment
      of osteoporotic vertebral body fractures, as well as in the palliative treatment
      of spinal metastases or symptomatic hemangiomas. It is usually performed under
      fluoroscopic, and often also CT control under analgesic sedation. If correctly
      indicated an analgesic effect occurs in roughly 90 % of patients. Epiduroscopy is
      a new technique, which is promising especially in patients with failed back
      surgery syndrome; patients with clinically-symptomatic fibrous adhesions,
      generally after repeated surgery. If correctly indicated a positive effect occurs
      in roughly one third to one half of patients.

PMID- 30189743
TI  - Interventional radiology therapies for liver cancer.
AB  - Radiological methods and procedures have become not only an inseparable part of
      the diagnosis of primary and secondary liver tumors, but also therapy and disease
      management of patients with colorectal cancer. The most common primary liver
      cancer, hepatocellular carcinoma, can be treated with curative intent by surgical
      approach as well as navigational radiological interventions. Palliative methods
      include transarterial chemoembolization, which is suitable for more than half of
      patients during treatment. extends treatment options even in patients with
      metastatic colorectal cancer who fail at standard therapies. In addition to
      thermal ablation in oligometastatic disease, intravascular procedures
      (chemoembolization and regional chemotherapy, preoperative portal vein
      embolization) can be used. By modern intervention approaches in patients with
      malignant biliary tract stenosis, we are able to refine and accelerate the
      diagnosis, to improve quality of life and to extend patients' survival.

PMID- 30189745
TI  - Imported skin parasitosis.
AB  - Larva migrans cutanea is a typical skin parasitosis of tropical and subtropical
      regions. In Central European countries, such as Slovakia and Czech Republic,
      larva migrans cutanea is just an imported disease. Its clinical symptoms are
      characterized by formation of erythematous focus with serpiginous morphology,
      which is caused by migration of helminth in epidermis. The disease does not
      threaten the patient's life, but causes significant discomfort, especially in
      form of pruritus in the affected area. Thanks to growing trend of today's tourism
      more tourists are exposed to the harmful effects of the environment in final
      destinations. This leads to an increase in frequency of imported diseases, with
      which physicians in our latitudes may not have enough experience.

PMID- 30189746
TI  - How do care staff in residential aged care facilities conceptualise their non
      verbal interactions with residents with dementia and what relevance has this for
      how residents' preferences and capacity for decision-making are understood?
AB  - This paper considers the significance of how staff in residential aged care
      facilities interpret the non-verbal communication and behaviour of residents vis
      a-vis their assessments of residents' preferences and ability to participate in
      decision-making. It highlights the risks associated with staff members' failure
      to interpret residents' non-verbal communication and behaviour with reference to
      residents' backgrounds and prior experiences. It also considers how non-verbal
      communication implemented by staff may impact residents' emotional state and, as
      a consequence, decision-making abilities. Drawing on interview data with aged
      care staff from Queensland and Victoria, it demonstrates that care staff in
      residential facilities appear to rely heavily on non-verbal signals in assessing
      the decision-making capacity and preferences of residents with dementia. It also
      indicates that many staff fail to consider residents' non-verbal communication
      and behaviour with due consideration of residents' individual histories.

PMID- 30189748
TI  - Predictive models for identifying risk of readmission after index hospitalization
      for heart failure: A systematic review.
AB  - AIMS:: Readmission rates for patients with heart failure have consistently
      remained high over the past two decades. As more electronic data, computing
      power, and newer statistical techniques become available, data-driven care could
      be achieved by creating predictive models for adverse outcomes such as
      readmissions. We therefore aimed to review models for predicting risk of
      readmission for patients admitted for heart failure. We also aimed to analyze and
      possibly group the predictors used across the models. METHODS:: Major electronic
      databases were searched to identify studies that examined correlation between
      readmission for heart failure and risk factors using multivariate models. We
      rigorously followed the review process using PRISMA methodology and other
      established criteria for quality assessment of the studies. RESULTS:: We did a
      detailed review of 334 papers and found 25 multivariate predictive models built
      using data from either health system or trials. A majority of models was built
      using multiple logistic regression followed by Cox proportional hazards
      regression. Some newer studies ventured into non-parametric and machine learning
      methods. Overall predictive accuracy with C-statistics ranged from 0.59 to 0.84.
      We examined significant predictors across the studies using clinical,
      administrative, and psychosocial groups. CONCLUSIONS:: Complex disease management
      and correspondingly increasing costs for heart failure are driving innovations in
      building risk prediction models for readmission. Large volumes of diverse
      electronic data and new statistical methods have improved the predictive power of
      the models over the past two decades. More work is needed for calibration,
      external validation, and deployment of such models for clinical use.

PMID- 30189749
TI  - Mortality Changes Associated with Mandated Public Reporting for Sepsis. The
      Results of the New York State Initiative.
AB  - RATIONALE: In 2013, the New York State Department of Health (NYSDOH) began a
      mandatory state-wide initiative to improve early recognition and treatment of
      severe sepsis and septic shock. OBJECTIVES: This study examines protocol
      initiation, 3-hour and 6-hour sepsis bundle completion, and risk-adjusted
      hospital mortality among adult patients with severe sepsis and septic shock.
      METHODS: Cohort analysis included all patients from all 185 hospitals in New York
      State reported to the NYSDOH from April 1, 2014, to June 30, 2016. A total of
      113,380 cases were submitted to NYSDOH, of which 91,357 hospitalizations from 183
      hospitals met study inclusion criteria. NYSDOH required all hospitals to submit
      and follow evidence-informed protocols (including elements of 3-h and 6-h sepsis
      bundles: lactate measurement, early blood cultures and antibiotic administration,
      fluids, and vasopressors) for early identification and treatment of severe sepsis
      or septic shock. MEASUREMENTS AND MAIN RESULTS: Compliance with elements of the
      sepsis bundles and risk-adjusted mortality were studied. Of 91,357 patients,
      74,293 (81.3%) had the sepsis protocol initiated. Among these individuals, 3-hour
      bundle compliance increased from 53.4% to 64.7% during the study period (P <
      0.001), whereas among those eligible for the 6-hour bundle (n = 35,307)
      compliance increased from 23.9% to 30.8% (P < 0.001). Risk-adjusted mortality
      decreased from 28.8% to 24.4% (P < 0.001) in patients among whom a sepsis
      protocol was initiated. Greater hospital compliance with 3-hour and 6-hour
      bundles was associated with shorter length of stay and lower risk and reliability
      adjusted mortality. CONCLUSIONS: New York's statewide initiative increased
      compliance with sepsis-performance measures. Risk-adjusted sepsis mortality
      decreased during the initiative and was associated with increased hospital-level
      compliance.

PMID- 30189747
TI  - Impact of Medicare Part D on mental health treatment and outcomes for dual
      eligible beneficiaries with HIV.
AB  - Depression is common among women with HIV and untreated depression can result in
      poor quality of life and worsen HIV outcomes. Women with HIV who are dually
      enrolled in Medicaid and Medicare faced a potential disruption in medication
      access when Medicare Part D was implemented in 2006. The goal of this study was
      to estimate the effects of Medicare Part D implementation on antidepressant use,
      depressive symptoms, and hospitalization in Medicaid-Medicare dual eligible women
      with HIV. This study used 2003-2008 data from the Women's Interagency HIV Study.
      The effects of Medicare Part D were estimated using a difference-in-differences
      approach, adjusting for temporal trends using a matched control group of Medicaid
      only enrollees. Before Medicare Part D implementation, dual eligibles differed
      from Medicaid-only enrollees in antidepressant use and hospitalization, despite
      having identical prescription drug coverage through Medicaid. For dual enrollees,
      the transition to Medicare Part D was not associated with changes in
      antidepressant use, depressive symptoms, or hospitalization. We did not find
      disruptive effects on antidepressant use and related outcomes among dual
      eligibles in this study. Stable antidepressant use may be due to better access to
      medical care for dual eligibles through Medicare both before and after Medicare
      Part D implementation, which may have eclipsed any effects of the transition. It
      may also signal that classification of antidepressants as a protected drug class
      under Medicare Part D was effective in preventing psychiatric medication
      disruption.

PMID- 30189750
TI  - HIV Vertical transmission in Rio de Janeiro, Brazil - does the distance matter?
AB  - Mother-to-child transmission (MTCT) is the main route of transmission for HIV
      among under 5 children in Brazil. National data indicate that missed
      opportunities for HIV prevention of MTCT are still common in antenatal care
      (ANC). We studied variables related to target process indicators in a cohort of
      HIV exposed children. We used data from 1996 to 2013 related to HIV exposed
      uninfected and HIV-infected children attended in an HIV reference hospital in Rio
      de Janeiro, Brazil. Data were collected from baseline questionnaires applied to
      all children followed-up in the hospital. Gestational and perinatal history were
      extracted from the mother's ANC card. Infants were categorized according to dates
      of first HIV care at the unit (1996-2000, 2001-2006 and 2007-2013). Distances
      between recorded addresses and the nearest maternity/hospital were measured by
      Euclidean distance, the shortest car route calculated in Google Maps and the
      route of the available bus line. Of the 599 children who fulfilled the inclusion
      criteria, 178 (29.7%) were HIV-infected. Approximately 70% of infants exposed to
      the virus from 1996-2000 were infected, dropping to 15.2% from 2001-2006 and
      rebounding to 30.1% from 2007-2013. Birth cohort was associated with ANC, and
      mothers from 2007-2013 had a lower chance of attending ANC (OR = 0.16; 95%CI 0.08
      0.30). In addition, when the distance home-birthplace was higher than 9.5 km,
      there was a lower chance that the mother had attended ANC (OR = 0.35; 95%CI 0.18
      0.68). Birth cohort was associated to HIV and ANC, and our data showed that a
      reduction of ANC might be related to rebound in HIV cases. There seems to have an
      association between larger distances from home to the birthplace and absence of
      ANC, which suggests that ANC was being performed in the tertiary units instead of
      in the primary care facilities as recommended.

PMID- 30189751
TI  - Mindfulness and emotion regulation: promoting well-being during the transition to
      college.
AB  - BACKGROUND AND OBJECTIVES: Managing stress is very important for first-year
      college students adjusting to undergraduate life. Aspects of emotion regulation,
      including mindfulness and the ability to regulate distressing emotion adaptively,
      often correlate positively with well-being. However, little research has examined
      overlapping and/or distinct effects of these constructs in predicting changes in
      adjustment over a stressful transition. Thus, the present study examined the
      contributions of mindfulness and adaptive emotion regulation abilities in
      maintaining well-being during the transition to college. We further examined
      experience with mind-body practices, which may promote mindfulness and positive
      adjustment. DESIGN: Online surveys were administered to 158 undergraduates near
      the beginning and end of their first semester. METHODS: Near semester start and
      end, students reported levels of mindfulness, adaptive emotion regulation
      abilities, emotional and spiritual well-being, and experience with mind-body
      practices. RESULTS: Compared to mindfulness, adaptive emotion regulation
      abilities largely demonstrated stronger cross-sectional and longitudinal
      associations with well-being. However, mindfulness uniquely protected against
      changes in depression for students with greater emotion regulation difficulties.
      Over half of participants reported having tried mind-body practices, but just 1%
      reported current use. CONCLUSIONS: Promoting mindfulness practices and adaptive
      emotion regulation abilities at the start of college may build resilience in
      undergraduate students.

PMID- 30189752
TI  - Corrigendum.

PMID- 30189753
TI  - The HNO- radical anion: A proposed intermediate in diazeniumdiolate synthesis
      using nitric oxide and alkoxides.
AB  - The strategy of synthesizing diazeniumdiolates (X-N(O)=NO-) through the
      coexistence of nitric oxide and alkoxides (RO-) was introduced by Wilhelm Traube
      120 years ago. Today, despite the wide use of diazeniumdiolate derivatives to
      release nitric oxide in the treatment of cancer, the first step of the reaction
      mechanism for diazeniumdiolate synthesis remains a mystery and is thought to be
      complex. We have studied the gas-phase reactions of nitric oxide with alkoxides
      at room temperature. An electron-coupled hydrogen transfer is observed, and the
      radical anion HNO- is the only ionic product in these reactions. HNO- can further
      react with nitric oxide to form N2O and HO-.

PMID- 30189754
TI  - Relative glycosidic bond stabilities of naturally occurring methylguanosines: 7
      methylation is intrinsically activating.
AB  - The frequency and diversity of posttranscriptional modifications add an
      additional layer of chemical complexity beyond canonical nucleic acid sequence.
      Methylations are particularly frequently occurring and often highly conserved
      throughout the kingdoms of life. However, the intricate functions of these
      modified nucleic acid constituents are often not fully understood. Systematic
      foundational research that reduces systems to their minimum constituents may aid
      in unraveling the complexities of nucleic acid biochemistry. Here, we examine the
      relative intrinsic N-glycosidic bond stabilities of guanosine and five naturally
      occurring methylguanosines (O2'-, 1-, 7-, N2,N2-di-, and N2,N2,O2'
      trimethylguanosine) probed by energy-resolved collision-induced dissociation
      tandem mass spectrometry and complemented with quantum chemical calculations.
      Apparent glycosidic bond stability is generally found to increase with increasing
      methyl substitution (canonical < mono- < di- < trimethylated). Many biochemical
      transformations, including base excision repair mechanisms, involve protonation
      and/or noncovalent interactions to increase nucleobase leaving-group ability. The
      protonated gas-phase methylguanosines require less activation energy for
      glycosidic bond cleavage than their sodium cationized forms. However, methylation
      at the N7 position intrinsically weakens the glycosidic bond of 7-methylguanosine
      more significantly than subsequent cationization, and thus 7-methylguanosine is
      suggested to be under perpetually activated conditions. N7 methylation also
      alters the nucleoside geometric preferences relative to the other systems,
      including the nucleobase orientation in the neutral form, sugar puckering in the
      protonated form, and the preferred protonation and sodium cation binding sites.
      All of the methylated guanosines examined here are predicted to have proton
      affinities and gas-phase basicities that exceed that of canonical guanosine.
      Additionally, the proton affinity and gas-phase basicity trends exhibit a roughly
      inverse correlation with the apparent glycosidic bond stabilities.

PMID- 30189755
TI  - Lack of association between lysyl oxidase-like 1 polymorphism in
      pseudoexfoliation syndrome and pseudoexfoliation glaucoma in North Indian
      population.
AB  - INTRODUCTION: Pseudoexfoliation syndrome is commonly associated with
      pseudoexfoliation glaucoma. The two nonsynonymous single-nucleotide polymorphisms
      rs1048661 (R141L) and rs3825942 (G153D) within exon 1 of LOXL1 gene have been
      found to confer risk of pseudoexfoliation syndrome and pseudoexfoliation glaucoma
      in different geographical populations. This study aims to find association
      between two nonsynonymous single-nucleotide polymorphisms with pseudoexfoliation
      syndrome and pseudoexfoliation glaucoma in North Indian population. METHODS:
      North Indian subjects clinically diagnosed with pseudoexfoliation
      syndrome/pseudoexfoliation glaucoma and normal age-matched control were enrolled
      in the study. Genomic DNA was extracted and the two single-nucleotide
      polymorphisms of LOXL1 gene were genotyped by polymerase chain reaction and
      sequencing. The association between single-nucleotide polymorphisms with
      pseudoexfoliation syndrome/pseudoexfoliation glaucoma was evaluated by chi-square
      test. RESULTS: A total of 30 pseudoexfoliation glaucoma, 27 pseudoexfoliation
      syndrome and 61 control subjects were enrolled in the study. Patients with
      pseudoexfoliation syndrome and pseudoexfoliation glaucoma did not show any
      genetic association with either single-nucleotide polymorphism rs1048661 or
      rs3825942. CONCLUSION: The study shows lack of association between LOXL1 single
      nucleotide polymorphisms and pseudoexfoliation in North Indian population.

PMID- 30189756
TI  - Administration of Nigella sativa during neonatal and juvenile growth period
      improved liver function of propylthiouracil-induced hypothyroid rats.
AB  - AIM: Propylthiouracil (PTU) is frequently used as an antithyroid medication. It
      is also commonly used to induce hypothyroidism in rodents. PTU administration and
      hypothyroidism have been shown to affect the liver function. Nigella sativa (NS)
      has been suggested to have antioxidant and hepatoprotective effects. The
      objective of this study was to investigate the effects of NS extract
      administration during neonatal and juvenile growth period on liver function of
      PTU-induced hypothyroid rats. METHODS: The pregnant rats were kept in separate
      cages. After delivery, the mothers and their offspring were randomly divided into
      five groups and were treated with the following programs: (1) control; (2) PTU,
      0.005% in their drinking water (3-5); PTU-plus 100, 200, or 400 mg/kg NS extract.
      After lactation period, the offspring continued to receive the same experimental
      treatment for the first 8 weeks of their life. Ten offspring of each group were
      randomly selected and weighted at days 10, 30, and 60 after delivery. Their blood
      samples were collected and the liver tissues were removed. RESULTS:
      Malondialdehyde (MDA) concentration was increased while, thiol concentration and
      superoxide dismutase (SOD) and catalase (CAT) activity were decreased in the
      liver tissues of PTU-treated rats. Serum aspartate amino transferase (AST),
      alkaline phosphatase (ALK-P), and alanine aminotransferase (ALT) levels in the
      PTU group were higher than the control group. Treatment with 200 and 400 mg/kg
      decreased MDA while increasing thiol concentration in the liver tissues compared
      to the PTU group. Treatment with all doses of the extract decreased serum ALK-P
      concentration compared with the PTU group. Treatment with 400 mg/kg NS increased
      CAT and SOD concentrations in the liver tissues and decreased serum AST and ALT
      concentrations compared to the PTU group. PTU decreased body weight gain of
      offspring and while, the extract increased the body weight gain of offspring
      rats. CONCLUSION: The results of this study demonstrated that administration of
      NS hydroalcoholic extract in the neonatal and juvenile growth period has an
      improving effect on the liver function of PTU- induced hypothyroid rats.

PMID- 30189757
TI  - Endovascular repair of an acute symptomatic carotid artery dissection through the
      false dissecting carotid lumen.
AB  - A 48-year-old woman presented with an acute ischemic stroke (National Institutes
      of Health Stroke Scale (NIHSS) 21) six hours after symptom onset. Workup revealed
      a left cervical internal carotid artery (ICA) occlusive dissection, which was
      emergently reconstructed with a flow-diverting stent. A routine Duplex scan one
      hour later suggested reocclusion of the ICA, confirmed by angiography. The true
      lumen of the ICA could not be accessed and therefore the "false lumen" of the ICA
      dissection was entered proximally. The true lumen and ultimately the flow
      diverting stent were accessed via the false lumen. In analogy to the subintimal
      arterial flossing with antegrade-retrograde intervention technique described for
      peripheral vascular disease, several stents were placed in telescoping fashion
      from the true common carotid lumen through the "false dissecting" lumen of the
      proximal ICA into the distal true lumen. The stent construct remained patent, and
      the patient recovered clinically to an NIHSS of 1.

PMID- 30189759
TI  - Let's Close the Gap Between Research and Practice to Discover New Land Together!

PMID- 30189758
TI  - Measuring fetal adipose tissue using 3D water-fat magnetic resonance imaging: a
      feasibility study.
AB  - PURPOSE: Analysis of fetal adipose tissue volumes may provide useful insight
      towards assessment of overall fetal health, especially in cases with abnormal
      fetal growth. Here, we assess whether fetal adipose tissue volume can be reliably
      measured using 3D water-fat MRI, using a quantitative assessment of the lipid
      content of tissues. MATERIALS AND METHODS: Seventeen women with singleton
      pregnancies underwent a fetal MRI and water-only and fat-only images were
      acquired (modified 2-point Dixon technique). Water and fat images were used to
      generate a fat signal fraction (fat/(water + fat)) from which subcutaneous
      adipose tissue was segmented along the fetal trunk. Inter-rater (three readers)
      and intrarater reliability was assessed using intraclass-correlation coefficients
      (ICC) for 10 image sets. Relationships between adipose tissue measurements and
      gestational age and estimated fetal weight percentiles were examined. RESULTS:
      The ICC of the inter-rater reliability was 0.936 (p < .001), and the ICC of the
      intrarater reliability was 0.992 (p < .001). Strong positive correlations were
      found between adipose tissue measurements (lipid volume, lipid volume/total fetal
      volume, mean fat signal fraction) and gestational age. CONCLUSIONS: 3D water-fat
      MRI can reliably measure volume and quantify lipid content of fetal subcutaneous
      adipose tissues.

PMID- 30189760
TI  - Sendai virus C protein limits NO production in infected RAW264.7 macrophages.
AB  - To suppress virus multiplication, infected macrophages produce NO. However, it
      remains unclear how infecting viruses then overcome NO challenge. In the present
      study, we report the effects of accessory protein C from Sendai virus (SeV), a
      prototypical paramyxovirus, on NO output. We found that in RAW264.7 murine
      macrophages, a mutant SeV without C protein (4C(-)) significantly enhanced
      inducible NO synthase (iNOS) expression and subsequent NO production compared to
      wild type SeV (wtSeV). SeV 4C(-) infection caused marked production of IFN-beta,
      which is involved in induction of iNOS expression via the JAK-STAT pathway.
      Addition of anti-IFN-beta Ab, however, resulted in only marginal suppression of
      NO production. In contrast, NF-kappaB, a primarily important factor for
      transcription of the iNOS gene, was also activated by 4C(-) infection but not
      wtSeV infection. Induction of NO production and iNOS expression by 4C(-) was
      significantly suppressed in cells constitutively expressing influenza virus NS1
      protein that can sequester double-stranded (ds)RNA, which triggers activation of
      signaling pathways leading to activation of NF-kappaB and IRF3. Therefore, C
      protein appears to suppress NF-kappaB activation to inhibit iNOS expression and
      subsequent NO production, possibly by limiting dsRNA generation in the context of
      viral infection.

PMID- 30189761
TI  - Intrauterine growth restriction associated with paternal isodisomy of chromosome
      5: a clinical report and literature survey.
AB  - BACKGROUND: Uniparental disomy (UPD) is a condition where both the chromosomes
      are inherited from the same parent. The consequences of UPD can be ranging from
      normal to congenital anomaly depending on the parental origin and chromosome
      involved. Case characteristics: Here, we describe a case of 2-year-old male with
      central hypotonia, torticollis, and delayed motor skills born to a
      nonconsanguineous healthy parent. The proband was prenatally detected with
      paternal isodisomy 5 and birth was induced at 38 weeks of gestation due to
      intrauterine growth restriction. There was also confined placental mosaicism
      along with the isodisomy. RESULTS: No major phenotypic correlation observed. This
      is the first case of paternal isodisomy 5 with phenotypically normal child.
      CONCLUSIONS: The present case supports the reports that genes on chromosome 5 are
      nonimprinted. The implications of abnormal genetic findings on genetic counseling
      are discussed.

PMID- 30189762
TI  - A Comparison of Adjusted Versus Unadjusted Doses of Polymyxin B Based on Renal
      Function and Incidence of Acute Kidney Injury.
AB  - PURPOSE: To determine whether or not polymyxin B needs dose adjustments based on
      renal function by comparing the incidence of acute kidney injury (AKI) in
      patients whose polymyxin B doses were adjusted versus not adjusted according to
      renal function. METHODS: This was a single-center, prospective study with a
      retrospective cohort taking place in an acute care community hospital. Forty-two
      patients treated with polymyxin B were evaluated between April 2012 and December
      2015. The primary outcome was incidence of AKI at day 7 after initiation of
      polymyxin B therapy with secondary outcomes including microbiological cure,
      clinical cure, and 30-day mortality. RESULTS: There was no difference in the
      incidence of AKI at day 7 in patients with polymyxin B doses adjusted according
      to renal function versus patients without polymyxin B dose adjustment (20.0% vs
      18.2%; P = .882). There were no differences between groups in occurrence of
      microbiological cure, clinical cure, or 30-day mortality (27.8% vs 57.1%; P =
      .065, 70.0% vs 72.7%; P = .845, 40.0% vs 31.8%; P = .581, respectively).
      CONCLUSION: The results from this study support the use of polymyxin B without
      any dose adjustment in the setting of renal impairment.

PMID- 30189763
TI  - Preparation and characterisation of flame retardant encapsulated with
      functionalised silica-based shell.
AB  - Intumescent fire retardant (IFR) coatings are nowadays considered as the most
      effective flame retardant (FR) treatment. Nevertheless, the principal compound in
      an IFR system, ammonium polyphosphate (APP), is highly sensitive to moisture and
      IFR coating effectiveness decreases quickly. The main objective of this study is
      to encapsulate APP in a hybrid silica-based membrane by sol-gel process using
      alkoxysilane tetraethoxysilane (TEOS) and methyltriethoxysilane (MTES) precursor.
      The morphology and structure of APP and microencapsulated ammonium polyphosphate
      (MAPP) were assessed by scanning electron microscopy and Fourier transforms
      infrared spectroscopy (FTIR). X-ray photoelectron spectroscopy (XPS) results
      revealed that APP was well encapsulated inside the polysiloxane shells. The
      thermal degradation of APP and MAPP was evaluated by thermogravimetric analysis.
      At 800  degrees C, the MAPP had higher char residue (70.49 wt%) than APP (3.06
      wt%). The hydrophobicity of MAPP increased significantly with the water contact
      angles up to 98 degrees , in comparison to 20 degrees  for APP.

PMID- 30189764
TI  - Intrapartum cervical lacerations and their impact on future pregnancy outcome.
AB  - OBJECTIVE: To investigate the significance of intrapartum cervical lacerations on
      subsequent pregnancies. STUDY DESIGN: A retrospective cohort analysis was
      conducted, comparing outcomes of subsequent singleton pregnancies, in women with
      and without a history of cervical lacerations in a previous delivery. Deliveries
      occurred between the years 1991-2014 at the Soroka University Medical Center.
      Multiple logistic regression models were constructed to control for clinically
      significant confounders. RESULTS: During the study period 187,162 deliveries met
      the inclusion criteria. Of them, 429 (0.2%) occurred in women with a history of
      cervical lacerations in the previous pregnancy (study group). The study group
      exhibited significantly higher rates of recurrent cervical lacerations (21/429,
      4.9% versus 275/187 162,0.1%, p value = .001), cerclage (13/429, 3% versus
      260/187 162, 0.1% p value = .001), cervical incompetence (8/429, 1.9% versus
      609/187 162, 0.3% p value = .001) cesarean delivery (CD) (97/429, 22.6% versus 26
      280/187 162,14%, p value = .001), severe perineal tears (third or fourth degree;
      2/429, 0.5%, versus 164/187 162, 0.1%, p value = .056) and blood transfusion
      (11/429, 2.6% versus 2448/187 162, 1.3%, p value = .022) as compared with the
      comparison group. Using a multivariable logistic regression model, history of
      cervical laceration in a previous pregnancy was found to be an independent risk
      factor for subsequent CD (OR 1.4, 95% CI 1.1-1.9), recurrent cervical laceration
      (OR 29.3, 95% CI 17.7-48.5), severe perineal lacerations (OR 11.7, 95% CI 5.1
      27.2), and preterm delivery (OR 1.8, 95% CI 1.1-2.8) in the subsequent pregnancy.
      CONCLUSIONS: A history of intrapartum cervical laceration is an independent risk
      factor for recurrent cervical lacerations, CD, preterm delivery, and severe
      perineal lacerations in the subsequent pregnancy.

PMID- 30189765
TI  - Reduced Versus Conventional Dose Insulin for Hyperkalemia Treatment.
AB  - BACKGROUND: Using a reduced dose of 5 units of regular insulin has been proposed
      as a strategy to mitigate the risk of hypoglycemia when treating hyperkalemia.
      The comparative efficacy and safety of this strategy to conventional 10 units is
      not well established. OBJECTIVE: To compare the effectiveness of reduced and
      conventional dosed insulin for hyperkalemia treatment. METHODS: Electronic
      medication administration reports of conventional or reduced doses of insulin
      given for hyperkalemia treatment were reviewed from July 2013 to September 2015.
      The primary outcome was reduction in serum potassium. RESULTS: Ninety-two
      administrations of reduced dose insulin and 309 administrations of conventional
      dose insulin were included. No significant difference was found in potassium
      reduction between the groups (-0.096 mmol/L, P value = .2210). Post hoc subgroup
      analysis of patients with serum potassium > 6 mmol/L revealed a lower reduction
      in potassium in the reduced dose group compared to the conventional dose group
      (difference: -0.238 mmol/L, P value = .018). CONCLUSIONS: Conventional dose
      insulin may be more effective than reduced dose regular insulin at baseline serum
      potassium levels >6 mmol/L in the treatment of hyperkalemia. Frequent monitoring
      of serum potassium and glucose after administration of insulin is necessary to
      confirm adequate response and avoidance of hypoglycemia.

PMID- 30189766
TI  - Early low molecular weight heparin for postpartum hemorrhage in women with pre
      eclampsia. Is it effective to prevent consumptive coagulopathy?
AB  - BACKGROUND: Postpartum hemorrhage has been one of the most common cause of
      maternal morbidity and mortality. An association between pre-eclampsia (PE) and
      postpartum hemorrhage has been shown in previous studies. The aim of this study
      was to compare some characteristics of postpartum hemorrhage between women with
      and without PE. METHODS: Some characteristics of postpartum hemorrhage were
      compared between women with (n = 34) and without PE (n = 34). Majority of the
      cases underwent low molecular heparin administration at postpartum eighth hour,
      however, in cases who did not give satisfactory responses to blood product
      transfusions, to block suspected disseminated intravascular coagulation (DIC)
      secondary to the PE induced vascular injury, low molecular weight heparins were
      started within 2 h of postpartum hemorrhage. Some characteristics of cases with
      and without PE and with and without early low molecular weight heparin
      administration were compared. RESULTS: There were five cases who needed massive
      transfusions in group with PE, conversely, no case required massive transfusion
      in group without PE (p < .05), in these five cases prophylactic dose low
      molecular weight heparin was started within 2 h of postpartum period, these cases
      determined according to the changes in hematocrit, platelet, and fibrinogen
      levels with corresponding transfusions. Mean systolic and diastolic blood
      pressures were significantly higher in PE group. Highest lactate dehydrogenase
      (LDH) level during follow up was significantly higher in group with PE. Mean
      numbers of erythrocyte, thrombocyte, and fibrinogen transfusions were
      significantly higher in PE group. Duration of hospital stay was also
      significantly higher in group with PE. CONCLUSIONS: Postpartum hemorrhage in
      women with PE may be resistant to blood product transfusions due to DIC and
      vicious cycle can be blocked by early low molecular weight heparin
      administration.

PMID- 30189767
TI  - Dietary and lifestyle predictors of folate insufficiency in non-supplemented
      German women.
AB  - Low folate status is a risk factor for birth defects. We studied concentrations
      of red blood cell (RBC)- and serum folate in 198 German women in relation to
      information on dietary folate intake, demographic and lifestyle factors. Median
      serum- and RBC-folate levels were; (14.7 and 589 nmol/L, respectively. Serum <
      7.0 nmol/L or RBC-folate < 405 nmol/L were observed in 3.5% and 18.7% of the
      women, respectively. Three per cent of the women had both lowered serum and RBC
      folate. Whereas RBC-folate > 952 nmol/L (optimal levels around conception) were
      observed in 9.6%. Serum- and RBC-folate were positively associated; they showed
      the expected correlations with homocysteine, but only weak correlations with
      folate intake. Younger age, lower fibre and higher carbohydrate intakes were
      associated with lower blood folate. Thus, folate intake of approximately 278 ug/d
      was not sufficient to achieve optimal folate status in young women. In
      conclusion, in the absence of fortification with folic acid, the majority of the
      women did not achieve folate status that is optimal for prevention of birth
      defects.

PMID- 30189768
TI  - Patient preferences for method of cesarean skin closure: secondary outcomes from
      a randomized trial.
AB  - OBJECTIVE: To assess patient preference for sutures or staples for cesarean wound
      closure. METHODS: This is a planned secondary analysis of a randomized controlled
      trial of 746 women in which suture and staples were compared for cesarean skin
      closure. Enrolled patients were asked to complete preoperative and postoperative
      surveys to assess preferred closure. Reasons for expressed preferences were
      elicited for each patient. Preferences were stratified by a number of cesarean
      deliveries (CD). We sought to determine if patients had a specific preference for
      wound closure due to personal experience or a personal belief that one method may
      be more beneficial with respect to pain and appearance. RESULTS: We surveyed 550
      patients preoperatively and 627 postoperatively. Women with a prior CD were more
      likely to have a skin closure preference compared with women having a primary CD
      (p < .05). Women who had a prior closure with suture rather than staples were
      significantly more likely to have a preference for the same wound closure method
      (p < .01). Avoiding the need for staple removal was the main reason women
      preferred suture closure, both preoperatively and postoperatively. The higher the
      number of the previous CD, the greater the preference for future closure with
      suture over staples (p < .05). CONCLUSIONS: Women undergoing cesarean delivery
      prefer suture as the method for skin closure compared with staples.

PMID- 30189769
TI  - Pregnancy outcomes in women with rheumatoid arthritis: a retrospective population
      based cohort study.
AB  - PURPOSE: To assess if pregnancies in women with rheumatoid arthritis (RA) are at
      a higher risk for adverse maternal and neonatal outcomes. MATERIALS AND METHODS:
      A retrospective cohort study was carried out using the Healthcare Cost and
      Utilization Project - National Inpatient Sample (HCUP-NIS) from the USA. All
      births that took place from 2004 to 2013 were identified and women were
      classified as having RA or not on the basis of ICD-9 coding. Unconditional
      logistic regression was used to evaluate the adjusted effect of RA on maternal
      and neonatal outcomes. RESULTS: Of the total 8,417,607 births in our cohort, 6068
      were among women with RA for an overall prevalence of 72 per 100,000 births.
      There was a steady increase in reported RA in pregnancy from 47 to 100 per
      100,000 over the 10-year study period. Compared with women without RA, women with
      RA were more likely to develop pre-eclampsia/eclampsia, gestational diabetes, to
      present with preterm premature rupture of membranes(PPROM), to experience
      placental abruption and placenta previa, and to deliver by caesarean section.
      Postpartum, RA-complicated pregnancies were associated with wound complications
      and thromboembolisms. Congenital anomalies, small for gestational age and preterm
      birth were more common in neonates of women with RA. CONCLUSION: RA in pregnancy
      is associated with a greater likelihood of adverse maternal and neonatal
      outcomes. Women with RA should be made aware of these risks and be followed as a
      high risk pregnancy.

PMID- 30189770
TI  - Do the children born after assisted reproductive technology have an increased
      risk of birth defects? A systematic review and meta-analysis.
AB  - BACKGROUND: Assisted reproductive technologies (ARTs) have made great progress.
      However, whether tube baby born after ART were at an increased risk of birth
      defects is not clear. OBJECTIVE: To assess whether the ART increases the risk of
      birth defects in children born after ART. SEARCH STRATEGY: Medline, Google
      Scholar, and the Cochrane Library were searched. SELECTION CRITERIA: Clinical
      trials that evaluate the risk of birth defect in children born after in vitro
      fertilization (IVF)/intracytoplasmic sperm injection (ICSI) and natural
      conceptions (NC) were included. The primary outcome was the prevalence of birth
      defects. DATA COLLECTION AND ANALYSIS: The relative risk was used as the summary
      measure with random effects model. We assessed heterogeneity between studies
      using the I2 index. MAIN RESULTS: Totally 46 studies were included. The pooled
      relative risk (RR) estimated suggested there was an increased risk of birth
      defects in ART compared with the NC group (RR: 1.40; 95% CI 1.31-1.49). Twenty
      and fifteen studies were included to compare the risk of birth defects between NC
      and IVF/ICSI, respectively. The results indicated that both IVF and ICSI increase
      the risk of birth defects (IVF: RR 1.25; 95% CI 1.12-1.40; ICSI: RR 1.29; 95% CI
      1.14-1.45). When subgroup according to plurality, 22 studies assessed the risk of
      birth defects after ART or NC in singletons and 15 studies evaluated the risk of
      birth defects in twins. The pooled RRs were 1.41 (95% CI 1.30-1.52) and 1.18 (95%
      CI 0.98-1.42), respectively. CONCLUSIONS: Children born after ART were at an
      increased risk of birth defects compared with NC. There was no difference in
      birth defects risk between ART twins and NC twins.

PMID- 30189772
TI  - Upper arm basilic vein elevation as a solution for forearm ulnar-basilic
      arteriovenous fistulae with cannulation problems.
AB  - BACKGROUND: Ulnar-basilic arteriovenous fistula is an alternative option when a
      radiocephalic arteriovenous fistula is not feasible. We review our technique of
      basilic vein transposition in the upper arm for difficult to puncture forearm
      ulnar-basilic non-transposed arteriovenous fistulae. Technical note: Three
      patients were referred for forearm ulnar-basilic arteriovenous fistulae with
      difficult cannulation where the forearm basilic vein was left in situ (non
      transposed). Surgeon performed ultrasound examination confirmed a patent
      arteriovenous fistula with adequate diameter and flow, draining to the basilic
      vein in the forearm and into the upper arm. Recurrent new and resolving hematomas
      were present surrounding the forearm basilic vein resulting from difficult
      cannulation issues and problems maintaining needle position due the posterior
      medial ulnar-basilic arteriovenous fistula position and mobility of the non
      transposed forearm basilic vein. A basilic vein transposition elevation procedure
      was performed in the upper arm starting at the level of the elbow to a few
      centimeters below the axilla. Branches of the dilated basilic vein were ligated,
      the median cutaneous nerve was preserved, and the vein was elevated from its
      native position to a superficial and anterior location. Although difficult,
      dialysis access had been continued in the forearm during a brief period and none
      required catheter placement. Reliable dialysis access was successfully initiated
      using the newly transposed basilic vein in the upper arm 3-4 weeks after the
      procedure, maintaining arterial inflow based on the original ulnar-basilic
      arteriovenous fistula anastomosis at the wrist. None of the patients required
      further interventions with follow-up of 8, 15, and 22 months.

PMID- 30189773
TI  - The Src homology and collagen A (ShcA) adaptor protein may participate in the
      pathogenesis of membranous lupus nephritis.
AB  - The Src homology and collagen A (ShcA) adaptor protein that binds to tyrosine
      kinase receptors. ShcA plays a role in insulin signaling, stress resistance and
      energy metabolism. The 66-kDa Src homology 2 domain-containing protein (p66shc)
      belongs to the ShcA family and has been associated with reactive oxygen species
      (ROS); increased ROS is involved in the pathology of lupus nephritis (LN).
      However, whether ShcA can act as a biomarker for oxidative injury in LN is
      unknown. This study is aimed to investigate the ShcA expression in kidney tissues
      from patients presenting with LN and the association between ShcA expression and
      clinical parameters. Renal biopsy tissues were obtained from 62 LN, 20 primary
      membranous nephropathy (MN) and 10 other secondary MN patients. ShcA was measured
      by immunofluorescence. The expression of ShcA in the membranous lupus nephritis
      (class V) group showed a higher trend but there were no significant differences
      compared with pure mesangial disease (class II) and proliferative (Class III/IV)
      lupus nephritis. ShcA deposits were negative in primary and other secondary MN.
      ShcA might act as a new biomarker and a diagnostic tool to identify membranous
      lupus nephritis with other MN.

PMID- 30189774
TI  - Gemcitabine delivered by fucoidan/chitosan nanoparticles presents increased
      toxicity over human breast cancer cells.
AB  - AIM: To produce marine-origin nanoparticles (NPs) aiming to develop more
      effective and tolerated therapies for breast cancer. MATERIALS & METHODS: NPs
      based in two marine-origin polymers (fucoidan and chitosan) were prepared by
      polyelectrolyte complexation, for the delivery of an antitumor drug model
      (gemcitabine [Gem]). RESULTS: Final formulation resulted in stable NPs around 115
      140 nm in size and with a polydispersity index less than 0.2. Gem was
      encapsulated at a maximum entrapment efficiency of 35-42%. Drug-release studies
      demonstrated that around 84% of Gem is released within 4 h. Cytotoxicity results
      of Gem-loaded NPs showed increased toxicity (around 25%) when compared with free
      Gem. CONCLUSION: The drug-loaded NPs present increased toxicity over human breast
      cancer cells without increasing toxic effects over endothelial cells.

PMID- 30189776
TI  - The effect of tourniquet type and thigh conicity on the length of hamstring
      autograft.
AB  - PURPOSE: We studied the effect of using wide contoured pneumatic tourniquet (PT)
      versus ultra-narrow sterile exsanguination tourniquet (SET) on the length of
      hamstring autograft for anterior cruciate ligament (ACL) reconstruction in
      patients with tubular and conical thighs. METHODS: Fifty-eight patients
      undergoing ACL reconstruction between 2012 and 2013 were assigned to either SET
      or PT groups. We measured the tendon graft length and width as well as the
      patients' height, weight, and thigh circumference of 10 cm proximal to the
      patella and the distance from the anterior-superior iliac spine to the medial
      malleolus (ASIS-MM). We defined the ratio between the ASIS-MM and the thigh
      circumference as the conicity index (CI). All grafts were measured after folding
      into half, and the found value was recorded as functional graft length (FGL).
      Tendon graft dimensions were correlated with the individual anthropometric data
      and with CI in each of the groups. RESULTS: PT was used in 34 patients and SET on
      24 patients. FGL was 12.7 +/- 0.84 mean + standard deviation for the SET group
      versus 11.5 +/- 1.61 for the PT group ( p = 0.0011) with a strong positive
      correlation between FGL and CI for the PT group ( R2 = 0.625; p = 2.6 * 10-8) but
      nonsignificant correlation for the SET ( R2 = 0.222). Graft thickness was
      correlated with the patient age ( R2 = 0.450) but not with CI or type of
      tourniquet used. We found the CI to be a better measure of thigh conicity than
      thigh circumference, length, height, weight, or body mass index individually.
      CONCLUSION: We conclude that using the SET which occupies less space on the thigh
      yielded significantly longer hamstring autologous ACL graft compared to the PT
      and the FGL became essentially independent from the CI when the SET was used.

PMID- 30189775
TI  - The incidence and distribution of primary fibula tumors and tumor-like lesions: A
      35-year experience.
AB  - PURPOSE: Primary bone tumors of the fibula are rare. There are only a few studies
      reporting the incidence, histologic, and anatomic distribution of primary fibula
      tumors. This study aimed to comprehensively report the incidence, presenting
      symptoms, and histologic tumor types with the anatomic and histologic
      distribution of primary bone tumors of the fibula. METHODS: Between January 1983
      and December 2017, 6457 primary bone tumors and tumor-like lesions were diagnosed
      and treated in our musculoskeletal oncology surgery clinic. Of these, 264 (4.08%)
      were primary bone tumors and tumor-like lesions of the fibula. We retrospectively
      reviewed patients' records, histopathology records, and radiologic images
      regarding age, gender, anatomic localization, histopathologic diagnosis, and
      treatment methods. RESULTS: There were 209 (79.2%) benign and 55 (20.8%)
      malignant lesions. The most common benign and malignant tumors were
      osteochondroma (51 of 209; 24.4%) and chondrosarcoma (16 of 55; 29.1%). The
      proximal fibula was the most common location for both benign and malignant tumors
      (141 of 209; 67.5% and 45 of 55; 81.8%, respectively), followed by the distal
      fibula (52 of 209; 24.9% and 8 of 55; 14.5%, respectively) and the diaphysis (17
      of 209; 8.14% and 2 of 55; 3.64%, respectively). CONCLUSION: The incidence of
      primary bone tumors is higher than that reported in previous studies. Benign
      lesions constitute the majority of cases. One-fifth of all cases are malignant.
      The most common anatomic site involving the primary fibula tumors is the proximal
      fibula. LEVEL OF EVIDENCE: III.

PMID- 30189778
TI  - Cisplatin Effects in Lung Adenocarcinoma-bearing Mice, Alone and in Combination
      with Erlotinib.
AB  - Cisplatin causes nephrotoxicity that can lead to the development of acute kidney
      injury or chronic kidney disease. However, the current mouse model of cisplatin
      nephrotoxicity is neither physiologically nor clinically relevant. Our goal was
      to improve upon these deficits by developing a repeated, low-dose regimen of
      cisplatin and combining it with a transgenic mouse model of lung adenocarcinoma.
      This overview details how addressing these deficits have improved our
      understanding of cisplatin-induced kidney injury.

PMID- 30189777
TI  - New Frontiers: Approaches to Understand the Mechanistic Basis of Renal Toxicity.
AB  - A scientific session entitled "New Frontiers: Approaches to Understand the
      Mechanistic Basis of Renal Toxicity" focused on novel biomarkers to monitor
      kidney injury both preclinically and clinically, as well as providing mechanistic
      insight of the induced injury. Further, the role and impact of kidney membrane
      transporters in drug-induced kidney toxicity provided additional considerations
      when understanding kidney injury and the complex role of drug transporters in
      either sensitivity or resistance to drug-induced injury. The onset of nephropathy
      in diabetic patients was also presented, focusing on the quest to discover novel
      biomarkers that would differentiate diabetic populations more susceptible to
      nephropathy and renal failure. The session highlighted exciting new research
      areas and novel biomarkers that will enhance our understanding of kidney injury
      and provide tools for ensuring patient safety clinically.

PMID- 30189779
TI  - Implicating a Temperature-Dependent Clock in the Regulation of Torpor Bout
      Duration in Classic Hibernation.
AB  - Syrian hamsters may present 2 types of torpor when exposed to ambient
      temperatures in the winter season, from 8 degrees C to 22 degrees C (short
      photoperiod). The first is daily torpor, which is controlled by the master
      circadian clock of the body, located in the SCN. In this paper, we show that
      daily torpor bout duration is unchanged over the 8 degrees C to 22 degrees C
      temperature range, as predicted from the thermal compensation of circadian
      clocks. These findings contrast with the second type of torpor: multi-day torpor
      or classic hibernation. In multi-day torpor, bout duration increases as
      temperature decreases, following Arrhenius thermodynamics. We found no evidence
      of hysteresis from metabolic inhibition and the process was thus reversible. As a
      confirmation, at any temperature, the arousal from multi-day torpor occurred at
      about the same subjective time given by this temperature-dependent clock. The
      temperature-dependent clock controls the reduced torpor metabolic rate while
      providing a reversible recovery of circadian synchronization on return to
      euthermy.

PMID- 30189780
TI  - Utility of the superficial radial nerve as donor for grafting of ipsilateral
      forearm nerve defects.

PMID- 30189781
TI  - Cefotetan-Induced Hemolytic Anemia: Case Series and Review.
AB  - PURPOSE: To raise awareness of cefotetan-induced hemolytic anemia, a known rare
      but serious side effect that occurred in 5 patients at our medical center.
      SUMMARY: Five cases of cefotetan-induced hemolytic anemia, which presented over
      the period of a single year at our center, are described. In each case, hemolytic
      anemia was confirmed by testing for the presence of anti-cefotetan antibodies.
      Each case occurred approximately 1 to 2 weeks following exposure to the drug. All
      five patients survived. A brief review of drug-induced immune hemolytic anemia
      (DIIHA) is also discussed. CONCLUSION: DIIHA may be difficult to distinguish from
      other causes of hemolytic anemia, but should be included in the differential in
      patients exposed to medications associated with DIIHA. Once suspected, antibody
      testing should be performed, and once diagnosed, further exposure should be
      avoided.

PMID- 30189783
TI  - Impact of Critical Care Transesophageal Echocardiography in Medical-Surgical ICU
      Patients: Characteristics and Results From 274 Consecutive Examinations.
AB  - OBJECTIVE: Critical care echocardiography has become an integral tool in the
      assessment and management of critically ill patients. Critical care
      transesophageal echocardiography (TEE) offers diagnostic reliability, superior
      image quality, and an expanded diagnostic scope to transthoracic
      echocardiography. Despite its favorable attributes, TEE use in North American
      intensive care units (ICUs) remains relatively undescribed. In this article, we
      seek to characterize the feasibility, indications, and clinical impact of a
      critical care TEE program. DESIGN: Retrospective, observational study. SETTING:
      Tertiary care, academic critical care program consisting of 2 hospitals in
      Ontario, Canada. PARTICIPANTS: Consecutive critical care TEE examinations on ICU
      patients performed between December 2012 and December 2016 Interventions: None.
      MEASUREMENTS AND MAIN RESULTS: Consecutive critical care TEE studies on ICU
      patients from December 1, 2012, to December 31, 2016, were reviewed. The TEEs
      performed on cardiac surgery patients and those without reports were excluded.
      Examination details, including indications, complications, examination complexity
      (number of views, Doppler techniques), and clinical recommendations were
      aggregated and analyzed. Two hundred seventy-four TEE studies were performed by
      38 operators. Common indications for TEE studies were hemodynamic instability
      (45.2%), assessment for infective endocarditis (22.2%), and cardiac arrest
      (20.1%). A change in patient management was proposed following 79.5% of TEE
      studies. Thirty-eight percent of TEE studies were performed during evening hours
      or on weekends. There were no mechanical complications. CONCLUSIONS: Our
      observational data support intensivist-performed TEE as being safe and
      therapeutically influential across a broad range of indications. Our program's
      demonstrated feasibility and impact may act as a model for TEE adoption in other
      North American ICUs.

PMID- 30189782
TI  - Effects of Medical Transport on Outcomes in Children Requiring Intensive Care.
AB  - BACKGROUND AND OBJECTIVES: The need to centralize patients for specialty care in
      the setting of regionalization may delay access to specialist services and
      compromise outcomes, particularly in a large geographic area. The aim of this
      study was to explore the effects of interhospital transferring of children
      requiring intensive care in a Canadian regionalization model. METHODS: A
      retrospective cohort design with a matched pair analysis was adopted to compare
      the outcomes in children younger than 17 years admitted to a pediatric intensive
      care unit (PICU) of a Canadian children's hospital by a specialized transport
      team (pediatric critical care transported [PCCT] group) and those children
      admitted directly to PICU from its pediatric emergency department (PED group).
      The outcomes of interest included mortality 72 hours from initial contact with
      the critical care team (ie, either PICU transport team or intrahospital PICU
      team). RESULTS: In total, 680 (27%) transports met our inclusion criteria,
      whereas 866 (7%) cases of 11 570 total PICU admissions were admitted directly
      from the emergency department. A total of 493 pairs were formed for the matched
      analyses. Odds of mortality within 72 hours in the PCCT group were significantly
      higher than in the PED group (odds ratio [OR]: 2.18, 95% confidence interval
      [CI]: 1.07-4.45; P = .032). When excluding cases who had at least one episode of
      cardiac arrest before involvement of the pediatric critical care (PCC) transport
      team, the OR dropped to 1.66 (95% CI: 0.77-3.46). CONCLUSIONS: Children
      transported from nonpediatric hospitals had a higher 72-hour mortality when
      compared to those children admitted directly to a children's hospital PICU from
      its own PED in a Canadian regionalized health-care model.

PMID- 30189784
TI  - More Reform of the English National Health Service: From Competition Back to
      Planning?
AB  - The period of sustained financial austerity since 2009 has led to a shift in
      competition policy within the English National Health Service. Policymakers have
      directed their attention away from the preexisting priority to support quicker
      access to routine and planned hospital care and have focused instead on improving
      emergency, cancer, and general practitioner services. This has prompted the
      development of a new policy framework and, in particular, a desire to create
      collaborative health systems focused on specific populations. In addition,
      previous policy initiatives to engage the leadership of general practitioners in
      planning services have been revisited. The overall effect has been to shift
      emphasis away from competitive markets and back toward a planning approach.

PMID- 30189785
TI  - Caring for Thai Older Persons With Long-Term Care Needs.
AB  - OBJECTIVE: To provide a situation analysis of recent long-term care (LTC) needs
      among older persons in Thailand. METHOD: The 2014 Survey of Older Persons in
      Thailand (SOPT) provides data to assess patterns of caregiving, whether care
      needs are met, and who are main caregivers for older Thais. We examine how types
      of familial and nonfamilial caregivers are associated with the well-being of
      older persons. RESULTS: The need for LTC increases sharply with age and is more
      common among women than men. Spouses and children constitute approximately 90% of
      main caregivers. The association of a family member as the main caregiver and
      education or value of assets is quite weak underscoring the general normative
      prescription for family members to serve as care providers. DISCUSSION: Thailand
      is experiencing acute population aging but empirical evidence to support LTC
      needs remains lacking. This analysis helps close the gap.

PMID- 30189786
TI  - Substituting Generic Lamivudine for Emtricitabine in Virologically Suppressed HIV
      Infected Patients.
AB  - This study evaluated the effectiveness of formulary substitution from products or
      regimens containing name brand emtricitabine to alternative regimens containing
      generic lamivudine among virologically suppressed HIV-infected patients in a
      correctional managed health care system. Results of this retrospective cohort
      study showed that 94.9% of patients switched from emtricitabine to lamivudine ( n
      = 447) and 93.0% of emtricitabine control patients ( n = 449) had an undetectable
      viral load at last available test over a 2-year period. The two groups also
      showed similar values for CD4 counts, compliance, discontinuation, and M184V
      mutation; however, a slightly greater proportion of lamivudine patients
      experienced respiratory symptoms. Nonetheless, this study demonstrates that
      switching virologically suppressed HIV-infected patients from name brand
      emtricitabine-containing regimens to generic lamivudine-based regimens may reduce
      costs without compromising safety or effectiveness in correctional managed health
      care systems with directly observed therapy.

PMID- 30189787
TI  - A Case Report of Anticoagulation Management in Acquired Hemophilia Associated
      With Levofloxacin.
AB  - PURPOSE: To report a case of acquired hemophilia secondary to levofloxacin and
      provide a guide for the use of anticoagulation in acute coronary syndrome. CASE
      SUMMARY: A 75-year-old female treated with levofloxacin presented with
      spontaneous bruising of the upper extremities. Levofloxacin was discontinued and
      the symptoms resolved. Thereafter, the spontaneous bruising recurred and
      progressed over a few weeks. The patient was treated with recombinant factor VIIA
      with a time to recuperation of 3 months. The patient was subsequently found to
      have ST-segment elevation for which they received unfractionated heparin,
      ticagrelor, and aspirin prior to bare metal stent placement. CONCLUSION:
      Hemophilia A is a rare disease associated with high morbidity and mortality. Case
      studies previously evaluating the association of levofloxacin with acquired
      hemophilia have shown causality. Initiating anticoagulation in patients with
      acquired hemophilia has long been a challenge to clinicians as evidence-based
      guidelines are lacking and bleeding risk may outweigh the benefit of
      anticoagulation. Furthermore, factor VIII deficiency does not provide additive
      protection against atherosclerotic plaque formation. This case report supports
      existing literature associating levofloxacin with acquired hemophilia. Due to the
      complication of life-threatening bleeds, familiarity with the treatment course
      following coronary events will allow patients with acquired hemophilia to be
      adequately and safely anticoagulated.

PMID- 30189788
TI  - Terminal Withdrawal of Mechanical Ventilation: A Hospice Perspective for the
      Intensivist.
AB  - The intensive care unit (ICU) and hospice inpatient unit (IPU) environments
      differ in many ways. Although both endeavor to provide the best care possible for
      their patients, the day-to-day goals of these environments are almost
      antithetical. Similarly, the experiences and expertise of the staff differ. When
      performing a similar clinical task, it may be addressed in different ways because
      each group is engrained in their primary day-to-day focus. Terminal withdrawal of
      mechanical ventilation is a procedure that is performed in both ICUs and some
      hospice IPUs. Previous examinations of this subject have been based largely upon
      the correlative background, practices, and perceptions of the ICU prescriber. The
      purpose of this review is to examine how the manner in which this procedure is
      performed in the hospice environment may differ in ways that the intensivist can
      incorporate into their own plan of care, or better appreciate when making the
      decision to remove mechanical ventilation in the critical care unit or transfer
      the patient to a hospice environment for the procedure to be completed.

PMID- 30189789
TI  - Ramsay Hunt syndrome: a rare complication of herpes zoster infection in a lung
      cancer patient.
AB  - OBJECTIVES: Ramsay Hunt syndrome (RHS) is a rare complication of varicella zoster
      virus (VZV) reactivation with high morbidity, requiring swift and specific
      treatment. METHODS: We discuss the epidemiology, diagnosis and treatment of RHS
      using a case report of a cancer patient who presented with disseminated VZV
      reactivation, including RHS. RESULTS: A 68-year old man with stage IV lung
      adenocarcinoma, for which he received pemetrexed maintenance chemotherapy,
      presented to the emergency department with a progressive skin rash despite broad
      spectrum antibiotics, vertigo, and diminished hearing. Valacyclovir was started
      for a varicella zoster virus (VZV) reactivation. Despite antiviral therapy, his
      symptoms progressed with late appearance of vesicles in the external ear canal,
      leading to a diagnosis of Ramsay Hunt syndrome (RHS). CONCLUSION: RHS is a rare
      complication of VZV reactivation and can lead to peripheral facial nerve palsy,
      hearing loss, vestibular problems, and vesicles in the dermatome of the cranial
      nerve. Timely initiation of steroids and antiviral therapy lead to recovery of
      the facial nerve in >75% of cases, although the optimal therapy is still unclear.

PMID- 30189790
TI  - Brief Synopsis: Review of Renal Tubule and Interstitial Anatomy and Physiology
      and Renal INHAND, SEND, and DIKI Nomenclature.
AB  - This article provides a synopsis of the first two presentations from the second
      scientific session of the 37th Annual Symposium of the Society of Toxicologic
      Pathology in Indianapolis, Indiana, on June 18, 2018; the session focused on
      acute kidney injury. The first presentation, given by Dr. Kevin McDorman, focused
      on "Fundamentals of Renal Tubule and Interstitial Anatomy and Physiology."
      Several common background findings from toxicity studies were additionally
      discussed. Lastly, factors that impact the relevance and usefulness of historical
      control data, such as quality and consistency of histopathology, were discussed.
      The second presentation, given by Dr. Torrie Crabbs, provided a review of
      International Harmonization of Nomenclature and Diagnostic Criteria (INHAND),
      Standard for Exchange of Nonclinical Data (SEND), and drug-induced kidney injury
      (DIKI) nomenclature. INHAND is a global collaborative project that provides
      internationally accepted standardized nomenclature and diagnostic criteria for
      proliferative and nonproliferative changes in laboratory animals in toxicity and
      carcinogenicity studies. SEND is currently a required standard for data
      submission to the Food and Drug Administration (FDA). Since the FDA has indicated
      its preference for INHAND nomenclature, SEND will predominately use INHAND
      terminology; thus, familiarity with INHAND terminology is critical for
      toxicologic pathologists. The diagnostic features of three common DIKI findings,
      in addition to several complicated INHAND terminologies, were reviewed.

PMID- 30189791
TI  - Beyond measurement: the drivers of disrespect and abuse in obstetric care.
AB  - Concerns about disrespect and abuse (D&A) experienced by women during
      institutional birth have become critical to the discourse on maternal health. The
      rapid growth of the field from diverse points of origin has given rise to
      multiple and, at times, confusing interpretations of D&A, pointing to the need
      for greater clarity in the concepts themselves. Furthermore, attention to
      measurement of the problem has been excessive when viewed in relation to the
      small amount of work on critical drivers of disrespect and abuse. This paper
      raises some key issues of conceptualisation and measurement for the field, puts
      forward a working definition, and explores two critical drivers of D&A -
      intersecting social and economic inequality, and the institutional structures and
      processes that frame the practice of obstetric care. By identifying gaps and
      raising questions about the deeper causes of D&A, we point to potentially
      fruitful directions for research and action.

PMID- 30189792
TI  - Anticoagulation strategy in patients with atrial fibrillation after carotid
      endarterectomy.
AB  - AIM: Carotid artery stenosis and atrial fibrillation are diseases of the aging
      patient population. Literature lacks precise anticoagulation treatment protocols
      for patients with atrial fibrillation following carotid endarterectomy. We
      present our experiences with anticoagulation strategy in this particular patient
      population. PATIENTS AND METHODS: Between June 2001-September 2017, 165 patients
      with chronic or paroxysmal atrial fibrillation out of 1594 cases from three
      different institutions whom received Coumadin and aspirin and required carotid
      endarterectomy were reviewed, respectively. Mean age was 63.4 +/- 7.9 years.
      Male/female ratio was 102/63. There were 67 diabetic and 138 hypertensive cases.
      RESULTS: Patients are followed a mean of 64.4 +/- 16.9 months. Early mortality
      occurred in two patients due to intracranial bleeding and heart failure. Another
      patient was lost due to intracerebral hemorrhage and 16 other patients died due
      to various causes in the late follow-up. Three patients required exploration
      against bleeding. CONCLUSION: Combination of warfarin with an aim to keep the INR
      value between 2 and 3, and aspirin at a dosage of 100 mg per day seemed feasible
      and in our modest patient cohort. Further studies including multicenter larger
      data are warranted in order to establish a precise anticoagulation treatment
      protocol for patients with atrial fibrillation after carotid endarterectomy.

PMID- 30189793
TI  - High post-operative pain scores despite multimodal analgesia in ambulatory
      anorectal surgery: a prospective cohort study.
AB  - BACKGROUND: Ambulatory surgery for anorectal procedures has become widely
      accepted. Recent reviews recommend a multimodal approach to pain management.
      However, these recommendations are largely based on single intervention studies.
      Our goal was to evaluate post-operative pain in patients receiving a multimodal
      analgesic regimen. METHODS: All patients undergoing an ambulatory anorectal
      procedure between December 2015 and September 2016 received a pain diary. Mean
      pain throughout the day and pain during defecation where recorded on day 0-14 and
      day 21 postoperatively using a numeric rating scale-11. Use of oral analgesics
      was also recorded. RESULTS: Forty-two patients completed the pain diary. The use
      of local anesthetic infiltration did not result in a significant difference in
      pain scores in this study. Patients who received written information on
      postoperative pain management and hygienic measures had higher intake of oral
      analgesics. Despite receiving multimodal analgesic treatment, patients undergoing
      surgery for hemorrhoids or anal fissures reported pain scores >=4 and used
      analgesics longer. CONCLUSION: A multimodal analgesic approach consisting of
      local anesthetic infiltration, multiple oral analgesics and written information
      seems to be insufficient for certain patient groups after ambulatory anorectal
      surgery. Especially patients undergoing surgery for hemorrhoids or an anal
      fissure should receive adequate analgesia. Pain during defecation is problematic
      and finding a solution for this problem remains challenging. Further research
      into the combined use of different analgesic modalities is recommended.

PMID- 30189794
TI  - Inference for the treatment effect in multiple-period cluster randomised trials
      when random effect correlation structure is misspecified.
AB  - Multiple-period cluster randomised trials, such as stepped wedge or cluster cross
      over trials, are being conducted with increasing frequency. In the design and
      analysis of these trials, it is necessary to specify the form of the within
      cluster correlation structure, and a common assumption is that the correlation
      between the outcomes of any pair of subjects within a cluster is identical. More
      complex models that allow for correlations within a cluster to decay over time
      have recently been suggested. However, most software packages cannot fit these
      models. As a result, practitioners may choose a simpler model. We analytically
      examine the impact of incorrectly omitting a decay in correlation on the variance
      of the treatment effect estimator and show that misspecification of the within
      cluster correlation structure can lead to incorrect conclusions regarding
      estimated treatment effects for stepped wedge and cluster crossover trials.

PMID- 30189795
TI  - Investigation of the molecular interactions of triclocarban with human serum
      albumin using multispectroscopies and molecular modeling.
AB  - Triclocarban (TCC), as a broad spectrum antibacterial agent widely used in
      personal care products, has recently been recognized as environmental pollutant
      with the potential of adversely affecting wildlife and human health. However, the
      behavior of TCC in blood circulatory system and the potential toxicity of TCC at
      the molecular level have been poorly investigated. In this study, the effect of
      TCC on human serum albumin (HSA) and the binding mechanism of TCC to HSA were
      examined using spectroscopic techniques and molecular modeling methods. The
      fluorescence results suggested that the fluorescence of HSA was quenched by TCC
      through a static quenching mechanism and nonradiation energy transfer, and TCC
      was bound to HSA with moderately strong binding affinity via hydrophobic
      interaction based on the analysis of the thermodynamic parameters. The site
      marker competitive experiments revealed that TCC bound into subdomain IIA (site
      I) of HSA. In addition, the results obtained from the circular dichroism, Fourier
      transform infrared (FT-IR), 8-anilino-1-naphthalenesulfonic acid fluorescence,
      synchronous fluorescence, three-dimensional fluorescence spectra and dynamic
      light scattering suggested the change in the microenvironment and conformation of
      HSA during the binding reaction. Finally, the best binding mode of TCC and
      specific interaction of TCC with amino acid residues were determined using
      molecular docking and molecular dynamics simulations. In a word, the present
      studies can provide a way to help us well understand the transport, distribution
      and toxicity effect of TCC when it diffused in the human body. Communicated by
      Ramaswamy H. Sarma.

PMID- 30189796
TI  - Eliminating systematic bias from case-crossover designs.
AB  - Case-crossover designs have been widely applied to epidemiological and medical
      investigations of associations between short-term exposures and risk of acute
      adverse health events. Much effort has been made in literature on understanding
      source of confounding and reducing systematic bias by reference-select
      strategies. In this paper, we explored the nature of bias in the ambi-directional
      and time-stratified case-crossover designs via simulation using actual air
      pollution data from urban Edmonton, Alberta, Canada. We further proposed a
      calibration approach for eliminating systematic bias in estimates (coefficient
      estimate, 95% confident interval, and p-value). Bias check for coefficient
      estimation, size check and power check for significance test were done via
      simulation experiments to show advantages of the calibrated case-crossover
      studies over the ones without calibration. An application was done to investigate
      associations between air pollutants and acute myocardial infarction
      hospitalizations in urban Edmonton. In conclusion, systematic bias in a case
      crossover design is often unavoidable, leading to an obvious bias in the
      estimated effect and an unreliable p value in the significance test. The proposed
      calibration technique provides an efficient approach to eliminating systematic
      bias in a case-crossover study.

PMID- 30189797
TI  - Acute Kidney Injury (AKI)-The Toxicologic Pathologist's Constant Companion.
AB  - This article provides a brief overview of the second scientific session of the
      37th Annual Symposium of the Society of Toxicologic Pathology in Indianapolis,
      Indiana, on June 18, 2018. The session was entitled "Acute Kidney Injury (AKI):
      The Toxicologic Pathologist's Constant Companion" and was co-chaired by Drs.
      Zaher Radi and Torrie Crabbs. The fundamentals of tubule and interstitial anatomy
      were covered by Dr. Kevin McDorman, followed by a review of International
      Harmonization of Nomenclature and Diagnostic Criteria, Standard for Exchange of
      Nonclinical Data, and Drug-Induced Kidney Injury terminology, which was presented
      by Dr. Torrie Crabbs. Dr. Bruce Molitoris gave a talk on renal hemodynamics,
      microcirculation, and ischemia. Advances and challenges on new therapies and
      clinical targets of AKI were presented by Dr. Brad Rovin, and the session ended
      with a review from Dr. Zaher Radi on immunopathology of AKI.

PMID- 30189798
TI  - Interaction structures as predictors of outcome in a naturalistic study of
      psychodynamic child psychotherapy.
AB  - OBJECTIVE: The first aim of this study was to identify interaction structures
      (IS), which refer to clusters of items characterizing the course of psychotherapy
      in terms of reciprocal interaction patterns between the therapist and the child,
      secondly to assess their trends over the course of treatment, and finally
      investigate which IS predict outcome in long-term psychodynamic child
      psychotherapy. METHOD: The sample included 52 children with externalizing and
      internalizing problems. 192 sessions were rated with the use of the Child
      Psychotherapy Q-Set (CPQ). Outcome was assessed with the Child Behavior Checklist
      (CBCL) Total Problems, and Children's Global Assessment Scale (CGAS). RESULTS: A
      principal components analysis resulted in four IS, theoretically named
      Therapeutic Alliance, Children's Emotion Expression, Child -Centered Technique
      and Psychodynamic Technique. Multilevel Modeling (MLM) analyses indicated
      significant linear growth on Psychodynamic Technique. Multiple regression
      analyses indicated that Psychodynamic Technique positively predicted changes on
      CBCL Total Problems and CGAS. In contrast, Child-Centered technique negatively
      predicted change on CBCL Total Problems, however follow up interaction analyses
      showed that externalizing children who received more Child-Centered technique
      showed more improvement on this scale. DISCUSSION: Findings point to empirically
      derived components of psychodynamic child psychotherapy and provide preliminary
      answers about which aspects may facilitate change. Clinical or methodological
      significance of this article: This is one of the first studies to identify core
      treatment processes in psychodynamic psychotherapy for children with
      externalizing and internalizing problems. We were able to identify empirically
      derived change processes that can be used in future research and provided
      preliminary answers about which aspects may facilitate change, taking into
      account specific pre-treatment sample characteristics, which provided further
      evidence that therapist techniques occur as part of a complex interaction with
      the children's characteristics. These findings highlight the importance of an
      investigative strategy to study "what works for whom", using a naturalistic
      process-outcome research design, in order to understand what specifically
      promotes therapeutic change.

PMID- 30189799
TI  - Evaluation of the Factor Structure of the Adolescent Stress Questionnaire in
      Chinese Adolescents.
AB  - This study evaluated the psychometric properties of the Chinese version of
      Adolescent Stress Questionnaire ( ASQ-CN) in a sample of Chinese middle school
      students ( N = 420; 52.14% boys and 47.86% girls). Iterated principal factor
      analysis and multiple-group principal components cluster analysis supported a six
      factor model with 42 items out of 58 items in the ASQ-CN. The internal
      consistency was from .82 to .90. Girls reported lower stress levels in one
      subscale, Stress of romantic relationship, whereas no gender differences were
      found in the other five subscales. Compared with other studies of the ASQ in
      Westernized countries, the ASQ-CN showed a distinct factor structure that may be
      explained by cross-cultural differences. Scales constructed from factor analysis
      related negatively to measures of mindfulness and positively to a measure of
      behavioral problems, suggesting that they were valid for Chinese adolescent
      stress. The study did not support a higher order construct of the ASQ-CN.
      Altogether, our findings suggest that the ASQ-CN is adequate for assessing
      stressors in Chinese adolescents.

PMID- 30189800
TI  - Stop Pushing Me Away: Relative Level of Facebook Addiction Is Associated With
      Implicit Approach Motivation for Facebook Stimuli.
AB  - The use of Facebook and other social media sites has increased to the point that
      some consider it to be a behavioral addiction. Previously, research has used the
      Approach-Avoidance Task to measure implicit approach and withdrawal tendencies in
      response to a variety of stimuli, including alcohol, desserts, cigarettes,
      spiders, and cannabis. When responding to these types of stimuli, individuals
      typically evidence an approach bias toward appetitive images and a withdrawal
      bias in response to undesirable and/or fearful stimuli. The present study was
      designed to test the validity of an adapted version of the Approach-Avoidance
      Task by investigating how self-reported Facebook addiction tendencies, measured
      via the Bergen Facebook Addiction Scale, predicted automatic approach tendencies
      toward Facebook-related stimuli using the Facebook-Approach-Avoidance Task.
      Participants with higher self-reported tendencies of Facebook addiction tended to
      approach Facebook-related stimuli faster. The present study is the first to
      indicate a relationship between self-reported Facebook addiction tendencies and
      implicit approach motivation using a behavioral measure. This finding provides
      initial support for the use of the Facebook-Approach-Avoidance Task as a measure
      of Facebook addiction, and further validation could lead to the development of
      additional assessment and training paradigms in the future.

PMID- 30189802
TI  - Citations for the Human Rights and Nursing Awards 2018.

PMID- 30189801
TI  - Emotional State Can Affect Inflammatory Responses to Pain Among Rheumatoid
      Arthritis Patients: Preliminary Findings.
AB  - In a novel pilot study, we investigated how emotional state is related to
      inflammatory responses to acute pain among women with rheumatoid arthritis. Nine
      women completed four 5-hour visits that varied only by manipulation of emotion
      (anger, sadness, happiness, vs. control); in each visit, acute pain was elicited,
      with blood draws at baseline, 10 minutes, 60 minutes, and 100 minutes post-pain.
      We examined the effects of within-subjects factors on circulating inflammatory
      biomarkers interleukin (IL)-6, IL-10, tumor necrosis factor-alpha, C-reactive
      protein, and cortisol. There was a main effect of state anger on IL-6, with
      higher reported anger associated with higher IL-6 across conditions. Further,
      there were several interactions between state emotion and condition. For example,
      when individuals reported higher state anger in the sadness condition compared to
      their own average, they showed higher levels of IL-6 and cortisol. Findings are
      discussed within a larger literature suggesting that mixed emotional states can
      contribute to psychological stress and inflammatory responses.

PMID- 30189803
TI  - Learning from Gosport: Deterring institutionalised deafness.

PMID- 30189804
TI  - No circular economy if current systemic failures are not addressed.

PMID- 30189805
TI  - Industry update covering May 2018.
AB  - The present Industry Update covers the period 1-31 May 2018. Sources of
      information included company press releases, regulatory and patent agency notices
      and various news websites. Regulatory approvals of this month include Novartis
      (Basel, Switzerland) and Amgen's (CA, USA), Aimovig as a preventive treatment for
      migraines and Breckenridge's (CO, USA) delayed-release capsules, Duloxetine. This
      month also saw DURECT (CA, USA) and Sandoz (Upper Bavaria, Germany) renegotiate
      their agreement for the development, manufacture and commercialization of the
      extended-release depot product POSIMIR(r). In early stage preclinical development
      news there were several articles published on the area of modified delivery of
      therapeutics, including across the blood-brain barrier and the development of a
      novel single dose vaccine for polio.

PMID- 30189806
TI  - Ibuprofen intercalation and release from different layered double hydroxides.
AB  - AIM: The chemical composition of layered double hydroxides (LDHs) affects their
      structure and properties. The method of ibuprofen (IBU) intercalation into LDHs
      may modify its release, reduce adverse effects and decrease the required dosing
      frequency. METHODOLOGY: This study investigates the effects of four different
      LDHs; MgAl-LDH, MgFe-LDH, NiAl-LDH and NiFe-LDH on in vitro release of IBU
      intercalated by coprecipitation and anionic-exchange. RESULTS: MgAl-LDH was the
      most crystalline and substitution of either cation decreased LDH order. Fourier
      transform infrared spectra and power x-ray diffractograms confirmed the
      intercalation of IBU within the lamellar structure of MgAl-LDH and MgFe-LDH.
      Intercalation of IBU by anion-exchange resulted in slower, partial, drug release
      compared with coprecipitation. CONCLUSION: The chemical composition of LDHs
      affects their crystallinity, IBU intercalation and subsequent release.

PMID- 30189807
TI  - Non-Procrustean pathways for complex generic drugs development.

PMID- 30189808
TI  - Development and in vitro evaluation of solid dispersions as strategy to improve
      albendazole biopharmaceutical behavior.
AB  - AIM: Solid dispersions using Poloxamer 407 as carrier were developed to improve
      albendazole (ABZ) solubility and dissolution profiles. METHODS: ABZ/poloxamer
      solid dispersions were prepared, and dissolution profiles were mathematically
      modeled and compared with physical mixtures, pharmaceutical ABZ and a commercial
      formulation. RESULTS: Poloxamer 407 increased exponentially ABZ solubility, in
      about 400% when 95% w/w of polymer compared with its absence. Solid dispersions
      initial dissolution rate was three to 20-fold higher than physical mixtures, the
      drug and the commercial formulation. All the solid dispersions required less than
      2.2 min to reach an 80% of ABZ dissolution, while the commercial formulation
      needed around 40 min. CONCLUSION: Solid dispersions improved ABZ solubility and
      dissolution rate, which could result in a faster absorption and an increased
      bioavailability.

PMID- 30189809
TI  - Nonlamellar liquid crystals: a new paradigm for the delivery of small molecules
      and bio-macromolecules.
AB  - The aim of this article is to collate the recent developments in the field of
      drug delivery, medical therapeutics and diagnostics specifically involving the
      nonlamellar liquid crystalline (NLC) systems. This review highlights different
      NLC phases having cubic, hexagonal and sponge internal structures, and their
      application in the field of drug delivery, such as dose reduction, toxicity
      reduction and therapeutic efficacy enhancement either in the form of
      nanoparticles, colloidal dispersion or gels. In addition, application of NLC
      systems as vehicles for peptides, proteins and as a theranostic system in cancer
      and other disease conditions is also elaborated, which is a growing platform of
      interest. Overall, the present review gives us a complete outlook on applications
      of NLC systems in the field of medicine.

PMID- 30189810
TI  - Industry update covering April 2018.

PMID- 30189811
TI  - Binary and ternary complexes of norfloxacin to improve the solubility of the
      active pharmaceutical ingredient.
AB  - AIM: Binary and ternary complexes with hydroxypropyl-beta-cyclodextrin
      (HPbetaCD), using glutamic acid (GA), proline or lysine as the third component,
      were developed to increase the solubility and the dissolution rate of norfloxacin
      (NOR). METHODS/RESULTS: Complexation was evaluated by phase solubility studies,
      obtaining the highest NOR solubility with GA and HPbetaCD. Thermal analysis
      suggested that different kinds of interactions occur among NOR, HPbetaCD and each
      amino acid, and when the systems were prepared by kneading or by means of freeze
      drying technique. Dissolution studies, performed on simulated gastric fluid and
      subsequent simulated intestinal fluid, showed the highest rate of NOR from NOR
      HPbetaCD-GA. CONCLUSION: NOR:HPbetaCD:GA was the best approach for improving the
      bioavailability of NOR.

PMID- 30189812
TI  - Bedside contrast-enhanced ultrasound diagnosing cessation of cerebral circulation
      in a neonate: A novel bedside diagnostic tool.
AB  - Imaging diagnosis of brain death is performed with either four-vessel cerebral
      angiography or radionuclide cerebral blood flow studies. Unfortunately, timely
      performance of either study at a critically ill period is not only cumbersome but
      not feasible in many cases. We present a case of a 6-month-old male three hours
      status post-cardiac arrest of unknown etiology who underwent contrast-enhanced
      ultrasound (CEUS) for diagnosis of near absent perfusion, or near brain death.
      The patient passed away 30 minutes after the exam and clinical diagnosis of brain
      death was confirmed. The case report highlights the utility of CEUS for diagnosis
      of brain death. This can have significant clinical implications in neonates who
      may not be eligible for commonly used, cumbersome radiologic studies for
      diagnosis of brain death.

PMID- 30189813
TI  - Compliance with compression therapy in primary chronic venous disease: Results
      from a tropical country.
AB  - Objectives To describe compliance rates of compression therapy in a cohort of
      patients with chronic venous disease and also to describe frequent causes of non
      compliance. Methods A total of 889 patients with primary chronic venous disease
      were prescribed compression therapy after being evaluated by vascular surgeons.
      Subjects had a first visit during which time compression therapy was prescribed
      in addition to a follow-up visit. Strength of compression, type, prescription
      duration, and reasons of non-compliance were queried at follow-up. Results Only
      31.8% of the patients reported wearing compression therapy as prescribed, 31.4%
      reported wearing compression most days, 28.3% reported wearing compression
      intermittently, and 8.5% of the patients reported not wearing compression at all.
      The main reasons of non-compliance were: uncomfortable (49.4%), too difficult to
      put on (34.5%), skin problems (itching) (21.5%), and unattractive (19.8%).
      Conclusions Compliance with compression therapy in chronic venous disease is
      still a subject of concern as most patients are not using compression therapy as
      prescribed.

PMID- 30189814
TI  - Mechanised cardiac massage.

PMID- 30189816
TI  - The silence of our friends.

PMID- 30189815
TI  - How do we eliminate, or reduce the incidence of, wrong-side anaesthetic blocks?

PMID- 30189817
TI  - Anaesthesia and awareness: searching for the truth about consciousness in
      Oblivion.

PMID- 30189818
TI  - Nutritional prehabilitation: physiological basis and clinical evidence.
AB  - In this narrative review, we describe the physiological basis for nutritional
      prehabilitation and evaluate the clinical evidence for its current roles in the
      perioperative period. Surgical stress and fasting induce insulin resistance as a
      result of altered mitochondrial function. Insulin resistance in the perioperative
      period leads to increased morbidity in a dose-dependent fashion, while
      preoperative carbohydrate loading attenuates insulin resistance, minimises
      protein loss and improves postoperative muscle function. Carbohydrate loading is
      an established practice in many countries and a key component of enhanced
      recovery after surgery (ERAS) programs, yet its independent effects on clinical
      outcomes remain unclear. Amino acid supplements may confer additional positive
      effects on a number of markers of clinical outcomes in the perioperative period,
      but their current role is also poorly defined. Clinical studies evaluating
      nutritional interventions have been marred by conflicting data, which may be due
      to small sample sizes, as well as heterogeneity of patients and surgical
      procedures. At present, it is known that carbohydrate loading is safe and
      improves patients' wellbeing, but does not appear to influence length of hospital
      stay or rate of postoperative complications. This should be appreciated before
      its routine inclusion in ERAS programs.

PMID- 30189819
TI  - Fasting or starving? Measurement of blood ketone levels in 100 fasted elective
      and emergency adult surgical patients at an Australian tertiary hospital.
AB  - Prolonged fasting leads to a shift from carbohydrate to fat as the primary energy
      source, resulting in the production of ketones such as beta-hydroxybutyrate.
      Hyperketonaemia and ketoacidosis have been observed in young children fasting for
      surgery. The aim of this study was to investigate ketonaemia in adults fasted for
      surgery. One hundred non-diabetic adults presenting for elective or emergency
      surgery were assessed for the presence of hyperketonaemia (beta-hydroxybutyrate
      levels more than 1 mmol/l), and the relationship between beta-hydroxybutyrate,
      blood glucose and fasting duration was investigated. Three of 100 patients
      demonstrated hyperketonaemia, one of whom had ingested a ketogenic supplement the
      evening prior to surgery. No patient demonstrated beta-hydroxybutyrate levels
      suggestive of ketoacidosis (above 3 mmol/l). No relationship between fasting
      duration and ketone or glucose levels was observed. We found no evidence that
      prolonged preoperative fasting led to beta-hydroxybutyrate levels consistent with
      ketoacidosis.

PMID- 30189820
TI  - Does a catheter over needle system reduce infusate leak in continuous peripheral
      nerve blockade: a randomised controlled trial.
AB  - Continuous peripheral nerve blockade is a common technique in the analgesic
      management for many procedures. Leakage of local anaesthetic from around the
      nerve catheter insertion site can increase the chance of catheter dislodgement,
      risks infective complications, and could divert anaesthetic away from the nerve
      causing the block to fail. We conducted a randomised controlled trial to assess
      whether the type of nerve catheter influenced local anaesthetic leak rate. One
      hundred and ten patients scheduled for elective unilateral total knee
      arthroplasty were randomised to receive a perineural catheter with either a
      catheter over needle (CON) system (Pajunk(r) E-Cath) (PAJUNK(r) GmbH,
      Medizintechnologie, Geisingen, Germany), or catheter through needle (CTN) system
      (Pajunk(r) SonoLong) (PAJUNK(r) GmbH, Medizintechnologie, Geisingen, Germany).
      There was no statistically significant difference in the rate of leaking
      catheters between groups (CON 1.8% versus CTN 3.7%; <i>P</i>=0.618), however, the
      overall leak rate was much lower than anticipated from pilot data. The CON system
      was on average faster to insert (CON 357 seconds versus CTN 482 seconds;
      <i>P</i>=0.004), but associated with poorer needle visibility under ultrasound
      (Likert scale 1-5, mean [SD], CON 3.31 [0.96] versus CTN 3.89 [0.84];
      <i>P</i>=0.001). All seven instances of inadvertent catheter dislodgement
      occurred in the CTN group (<i>P</i>=0.006). There was no statistically
      significant difference between groups in the proportion of patients who had
      adequate analgesia on day one (CON 80% versus CTN 86.5%; <i>P</i>=0.294) and day
      two postoperatively (CON 85.5% versus CTN 91.8%; <i>P</i>=0.369). Our findings
      show the overall leak rate to be very low with both catheter systems; however,
      the CON system may have advantages in terms of speed of use and rate of
      inadvertent catheter dislodgement.

PMID- 30189822
TI  - Inhalational versus propofol-based total intravenous anaesthesia: practice
      patterns and perspectives among Australasian anaesthetists.
AB  - Increasing evidence suggests that total intravenous anaesthesia (TIVA) may be the
      preferred anaesthetic for cancer resection surgery. To assist the preparation of
      a randomised controlled trial (RCT) examining Volatile (versus TIVA) Anaesthesia
      and Perioperative Outcomes Related to Cancer (VAPOR-C) we developed an 18
      question electronic survey to investigate practice patterns and perspectives
      (emphasising indications, barriers, and impact on cancer outcomes) of TIVA versus
      inhalational general anaesthesia in Australasia. The survey was emailed to 1,000
      (of 5,300 active Fellows) randomly selected Australian and New Zealand College of
      Anaesthetists (ANZCA) Fellows. The response rate was 27.5% (n=275). Of the
      respondents, 18% use TIVA for the majority of cases. In contrast, 46% use TIVA
      20% of the time or less. Respondents described indications for TIVA as high risk
      of nausea, neurosurgery, and susceptibility to malignant hyperthermia. Lack of
      equipment, lack of education and cost were not considered barriers to TIVA use,
      and a significant proportion (41%) of respondents would use TIVA more often if
      setup were easier. Of the respondents, 43% thought that TIVA was associated with
      less cancer recurrence than inhalational anaesthesia, while 46% thought that
      there was no difference. Yet, only 29% of respondents reported that they use TIVA
      often or very often for cancer surgery. In Australasia, there is generally a low
      frequency of TIVA use despite a perception of benefit when compared with
      inhalational anaesthesia. Anaesthetists are willing to use TIVA for indications
      where sufficient evidence supports a meaningful level of improvement in clinical
      outcome. The survey explores attitudes towards use of TIVA for cancer surgery and
      demonstrates equipoise in anaesthetists' opinions regarding this indication. The
      inconsistent use of TIVA in Australasia, minimal barriers to its use, and the
      equipoise in anaesthetists' opinions regarding the effect of TIVA versus
      inhalational anaesthesia on cancer outcomes support the need for a large
      prospective RCT.

PMID- 30189821
TI  - A randomised controlled trial comparing fibreoptic-guided tracheal intubation
      through two supraglottic devices: Ambu(r) AuraGainTM laryngeal mask and LMA(r)
      FastrachTM.
AB  - The Ambu(r)AuraGainTM laryngeal mask (LM) (Ambu A/S, Ballerup, Denmark) is one of
      the few readily available second-generation supraglottic airway devices (SADs)
      that offer a conduit for fibreoptic-guided endotracheal intubation. We aimed to
      compare fibreoptic intubation through this device with the LMA(r) (laryngeal mask
      airway) FastrachTM (Teleflex Medical, Co. Westmeath, Ireland), which has been a
      recommended dedicated rescue device for the management of the unanticipated
      difficult airway. This randomised controlled trial compared a previously
      described fibreoptic score in 116 patients with no known airway pathology, who
      had asleep fibreoptic endotracheal intubation via either the AuraGain LM or the
      LMA Fastrach. Time, ease and success rate of SAD and endotracheal tube (ETT)
      insertion and complications were recorded. The AuraGain LM demonstrated better
      laryngeal alignment with 29 out of 59 patients in the AuraGain LM (AG) group
      having a Grade 4 view (only vocal cords visible), compared to 20 out of 54
      patients in the LMA Fastrach (FT) group (<i>P</i>=0.003). It allowed
      significantly quicker and easier ETT intubation when used as a conduit. The
      AuraGain LM was also quicker to insert compared to the Fastrach LMA. Similar
      rates of minor complications, such as sore throat and dysphonia occurred in both
      groups. Our study indicates that when used in patients with complete muscle
      relaxation and no known airway pathology, the AuraGain LM achieves better
      laryngeal alignment and quicker, easier and more successful fibreoptic-guided ETT
      intubation than the Fastrach LMA.

PMID- 30189823
TI  - Attitudes and self-reported end-of-life care of Australian and New Zealand
      intensive care doctors in the context of organ donation after circulatory death.
AB  - The incidence of organ donation after circulatory death (DCD) in Australia and
      New Zealand (ANZ) has steadily increased in recent years. Intensive care doctors
      are vital to the implementation of DCD and healthcare professionals' attitudes to
      DCD can influence their participation. In order to determine ANZ intensive care
      doctors' attitudes to DCD, to explore if demographic characteristics influence
      attitude to DCD and to assess if attitude to DCD can predict palliative
      prescription rationale at the end of life of DCD donors, a cross-sectional online
      survey was distributed to ANZ intensive care doctors and responses collected
      between 29 April and 10 June 2016. Exploratory factor analysis was used to define
      various attributes of attitude to DCD. Results were subjected to comparative
      statistical analyses to examine the relation between demographic data and
      attitude to DCD. Multiple regression models were used to examine if attitude to
      DCD could predict intensive care doctors' palliative prescription rationales at
      the end of life of DCD donors. One hundred and sixty-one intensive care doctors
      responded to the survey with 69.4% having worked in intensive care for ten years
      or more. Respondents responded positively to the support of and perceived
      importance of DCD in helping those who would benefit from the donations
      (constructive attributes)(mean composite factor score = 3.84, standard deviation
      [SD] 0.83), they positively perceived that conducive and facilitative
      orchestration of DCD helps families cope (mean composite factor score = 3.94, SD
      0.72) and that they would manage a DCD donor similar to any patient at the end of
      their life (mean score = 3.94, SD 0.72). Respondents responded negatively to
      having concerns that the circulatory death of potential DCD donors does not occur
      within the specified time frame (mean score = 2.28, SD 1.02). There was an
      association between organ donation professional education courses, familiarity
      with national guidelines and positive attitudes to certain attributes of attitude
      to DCD. Regression models demonstrated the attitude to DCD may predict intensive
      care doctors' palliative medication prescription rationales at the end of life of
      the DCD donor. Intensive care doctors in ANZ adopt a morally neutral attitude to
      DCD where they recognise the importance of organ donation, and support and
      conduct DCD as a part of good end-of-life care.

PMID- 30189824
TI  - An audit of perioperative blood transfusions in a regional hospital to
      rationalise a maximum surgical blood ordering schedule.
AB  - Appropriate preoperative blood typing and cross-matching is an important quality
      improvement target to minimise costs and rationalise the use of blood bank
      resources. This can be facilitated using a maximum surgical blood ordering
      schedule (MSBOS) for specific operations. It is recommended that individual
      hospitals develop a site-specific MSBOS based on institutional data, but this is
      challenging in non-tertiary centres without electronic databases. Our aim was to
      audit our perioperative blood transfusions to develop a site-specific MSBOS. A
      retrospective audit of blood transfusions in surgical patients in our regional
      referral hospital was conducted using five years' coded administrative data.
      Procedures with higher transfusion rates warranting preoperative testing (type
      and screen with or without subsequent cross-matching) were identified. There were
      about 15,000 eligible surgical procedures performed in our institution over the
      audit period. The need for preoperative testing was identified for only a few
      procedures, namely laparotomy, bowel resection, major amputation, joint
      arthroplasty, hip/femur fracture and humerus surgery, and procedures for
      obstetric complications. We observed a reduction in transfusion rates over time
      for total joint arthroplasty. The use of coding data represents an efficient
      method by which centres without electronic anaesthesia information management
      systems can conduct large-scale audits to develop a site-specific MSBOS. This
      would represent a significant improvement for hospitals that currently base
      preoperative testing recommendations on expert opinion alone. As many procedures
      in regional centres have very low transfusion rates, hospitals with a similar
      case mix to ours could consider selectively auditing higher-risk operations where
      local data is most likely to alter testing recommendations.

PMID- 30189825
TI  - Introduction of a mandatory pre-block safety checklist into a regional
      anaesthesia block room service: a quality improvement project.
AB  - Wrong-side block is an uncommon yet potentially preventable complication of
      regional anaesthesia. One strategy for reducing the incidence of wrong-side block
      is to introduce an additional check into the pre-block workflow in the form of a
      block 'time out' or 'stop before you block'. In the aftermath of a wrong-side
      block incident at our institution, the mandatory use of a pre-block safety
      checklist was successfully introduced into the workflow of the block room.
      Compliance with the checklist rose from 31% in the six-month pre-intervention
      phase to over 90% in the six-month post-intervention phase. This was achieved
      without any negative effect on block efficacy, theatre efficiency, complication
      rates or patient satisfaction. The high rate of checklist utilisation was
      associated with an increased rate of ultrasound video documentation. This
      suggests that there may be collateral benefit to using a pre-block safety
      checklist in addition to merely reducing the risk of wrong-side block.

PMID- 30189826
TI  - A survey of the impact of patient adverse events and near misses on anaesthetists
      in Australia and New Zealand.
AB  - We conducted a cross-sectional online survey of members of the Australian and New
      Zealand College of Anaesthetists to investigate their experiences of adverse
      patient safety events and near misses, including their use of incident reporting
      systems and the organisational support available. There were 247 respondents. Of
      the 243 anaesthetists whose patients had an adverse event or near miss, 199
      reported this had affected them personally or professionally; 177 reported
      stress, 153 anxiety, 109 sleep disturbance, and 127 lower professional
      confidence. Of 188 who had reported an adverse event using their local incident
      reporting systems, 68 were satisfied with this process, 136 received useful
      feedback, 114 saw local improvements, and 104 saw system changes. Two hundred and
      thirty-four reported feeling determined to improve, and 228 were anxious about
      the potential for future errors. Seventy-five anaesthetists admitted not
      reporting a safety incident that they knew they should have. Reasons for not
      reporting included an impression that nothing would improve from incident
      reporting, that reporting was onerous, or fears of punitive action. These
      findings should spur anaesthetists, anaesthetic departments and professional
      organisations across Australia and New Zealand to examine their support
      mechanisms in relation to adverse events and errors and their incident reporting
      mechanisms, and to attempt to improve these services where necessary.

PMID- 30189827
TI  - Potential consequences of high-dose infusion of ketamine for refractory status
      epilepticus: case reports and systematic literature review.
AB  - Our goal was to provide comprehensive data on the effectiveness of ketamine in
      refractory status epilepticus (RSE) and to describe the potential consequences of
      long-term ketamine infusion. Ketamine, an N-methyl D-aspartate (NMDA) receptor
      antagonist, blocks excitatory pathways contributing to ongoing seizure. While
      ketamine use is standard in anaesthetic induction, no definitive protocol exists
      for its use in RSE, and little is known about its adverse effects in long-term,
      high-dose administration. We present two cases of RSE that responded rapidly to
      ketamine infusion, both with fatal outcomes secondary to metabolic acidosis and
      cardiovascular collapse. We performed a systematic review of the application and
      consequences of ketamine use in RSE. PubMed, Ovid, MEDLINE and PMC were searched
      for articles describing ketamine treatment for RSE according to a predetermined
      search strategy and inclusion criteria. The systematic review revealed wide
      discrepancies in ketamine dosing (infusion maintenance dose range 0.0075-10.5
      mg/kg/hour), but good outcomes in medically managed RSE (75% of studies reported
      moderate or complete seizure control in adults, 62.5% in paediatrics).
      Additionally, literature review elucidated a potentially causal relationship
      between prolonged ketamine infusion and both cardiovascular and metabolic
      dysregulation. Ketamine is effective in RSE by antagonising excitotoxic NMDA
      receptors. However, there is high variability in ketamine dosing and scarce data
      on its safety in long-term infusion. Metabolic acidosis and haemodynamic
      instability associated with the use of long-term, high-dose ketamine infusions
      must be of concern to clinicians administering ketamine to critically ill
      patients.

PMID- 30189829
TI  - Time for a collaborative approach to airway training.

PMID- 30189828
TI  - Evaluation of a new bougie design for the difficult airway: a manikin crossover
      trial.

PMID- 30189830
TI  - Parasitic infections in the intensive care unit.

PMID- 30189831
TI  - Delftia sp. LCW, a strain isolated from a constructed wetland shows novel
      properties for dimethylphenol isomers degradation.
AB  - BACKGROUND: Dimethylphenols (DMP) are toxic compounds with high environmental
      mobility in water and one of the main constituents of effluents from petro- and
      carbochemical industry. Over the last few decades, the use of constructed
      wetlands (CW) has been extended from domestic to industrial wastewater
      treatments, including petro-carbochemical effluents. In these systems, the main
      role during the transformation and mineralization of organic pollutants is played
      by microorganisms. Therefore, understanding the bacterial degradation processes
      of isolated strains from CWs is an important approach to further improvements of
      biodegradation processes in these treatment systems. RESULTS: In this study,
      bacterial isolation from a pilot scale constructed wetland fed with phenols led
      to the identification of Delftia sp. LCW as a DMP degrading strain. The strain
      was able to use the o-xylenols 3,4-DMP and 2,3-DMP as sole carbon and energy
      sources. In addition, 3,4-DMP provided as a co-substrate had an effect on the
      transformation of other four DMP isomers. Based on the detection of the genes,
      proteins, and the inferred phylogenetic relationships of the detected genes with
      other reported functional proteins, we found that the phenol hydroxylase of
      Delftia sp. LCW is induced by 3,4-DMP and it is responsible for the first
      oxidation of the aromatic ring of 3,4-, 2,3-, 2,4-, 2,5- and 3,5-DMP. The enzyme
      may also catalyze both monooxygenation reactions during the degradation of
      benzene. Proteome data led to the identification of catechol meta cleavage
      pathway enzymes during the growth on ortho DMP, and validated that cleavage of
      the aromatic rings of 2,5- and 3,5-DMPs does not result in mineralization. In
      addition, the tolerance of the strain to high concentrations of DMP, especially
      to 3,4-DMP was higher than that of other reported microorganisms from activated
      sludge treating phenols. CONCLUSIONS: LCW strain was able to degraded complex
      aromatics compounds. DMPs and benzene are reported for the first time to be
      degraded by a member of Delftia genus. In addition, LCW degraded DMPs with a
      first oxidation of the aromatic rings by a phenol hydroxylase, followed by a
      further meta cleavage pathway. The higher resistance to DMP toxicity, the ability
      to degrade and transform DMP isomers and the origin as a rhizosphere bacterium
      from wastewater systems, make LCW a suitable candidate to be used in
      bioremediation of complex DMP mixtures in CWs systems.

PMID- 30189832
TI  - Classification based on extensions of LS-PLS using logistic regression:
      application to clinical and multiple genomic data.
AB  - BACKGROUND: To address high-dimensional genomic data, most of the proposed
      prediction methods make use of genomic data alone without considering clinical
      data, which are often available and known to have predictive value. Recent
      studies suggest that combining clinical and genomic information may improve
      predictions. We consider here methods for classification purposes that
      simultaneously use both types of variables but apply dimensionality reduction
      only to the high-dimensional genomic ones. RESULTS: Using partial least squares
      (PLS), we propose some one-step approaches based on three extensions of the least
      squares (LS)-PLS method for logistic regression. A comparison of their prediction
      performances via a simulation and on real data sets from cancer studies is
      conducted. CONCLUSION: In general, those methods using only clinical data or only
      genomic data perform poorly. The advantage of using LS-PLS methods for
      classification and their performances are shown and then used to analyze clinical
      and genomic data. The corresponding prediction results are encouraging and stable
      regardless of the data set and/or number of selected features. These extensions
      have been implemented in the R package lsplsGlm to enhance their use.

PMID- 30189833
TI  - Codon usage and modular interactions between messenger RNA coding regions and
      small RNAs in Escherichia coli.
AB  - BACKGROUND: Small RNAs (sRNAs) are key regulators of gene expression in bacteria.
      In addition to modulating translation initiation, sRNAs can interact with mRNA
      coding regions to regulate mRNA stability and translation efficiency, enhancing
      or impeding progression of the ribosome along the mRNA. Since most amino acids
      are decoded by more than one codon (synonymous) we asked as to whether there is a
      codon bias in the interaction of sRNAs with coding regions of mRNAs. Therefore,
      we explored whether there are differences in codon usage or tRNA availability
      according to whether an mRNA is regulated by sRNAs or not. We also explored these
      parameters in the coding interaction regions in mRNAs. We focused our analysis on
      sRNAs that regulate multiple mRNAs. RESULTS: We found differences in codon
      adaptation index and tRNA adaptation index between sRNA-regulated and non-sRNA
      regulated mRNAs. Interestingly, the sRNA-mRNA interacting regions tended to be
      enriched in unpreferred codons decoded by scarce tRNAs. We also found that sRNAs
      with multiple targets often contained modular segments capable of recognizing
      conserved motifs among these mRNAs. CONCLUSIONS: Our results show that sRNAs in
      E. coli tend to recognize mRNA coding regions in which the ribosome is predicted
      to advance at low speeds. Identified motifs in interacting regions are conserved
      among mRNAs that are recognized by the same sRNA.

PMID- 30189834
TI  - Effects of mixed lactic acid bacteria on intestinal microbiota of mice infected
      with Staphylococcus aureus.
AB  - BACKGROUND: The stability of intestinal microorganisms plays an important role in
      human health, as the intestines perform important functions in the human body.
      Staphylococcus aureus is a Gram-positive, facultative anaerobic bacteria, it
      causes human infection worldwide, and is a major pathogen that causes intestinal
      infection. Mixed lactic acid bacteria (LAB) may have potential in the prevention
      and treatment of S. aureus infection. In the present study, we examined the
      effects of mixed LAB treatment on intestinal microbiota modulation in mice
      infected with S. aureus. RESULTS: High-throughput sequencing of the V3-V4 region
      of the bacterial 16S rRNA gene showed that the mixed LAB maintained the richness
      and diversity of the microbiota in the mouse intestine. By establishing
      operational taxonomic units and using rarefaction analysis, rank-abundance
      distribution curves, heat maps, Venn diagrams, bacterial community structures,
      and hierarchical clustering analysis, Bacteroidales, Lachnospiraceae, Bacteroides
      and Prevotellaceae were the most abundant taxa in the samples, we found that the
      composition of the intestinal microbiota was similar between the protection group
      administered mixed LAB and the negative control group. CONCLUSIONS:
      Staphylococcus aureus destroys the stable intestinal microbiota structure of
      mice, treatment with mixed LAB could prevent S. aureus infection in mice and
      improve the structure of the intestinal microbiota.

PMID- 30189835
TI  - Long-term effects of the SLC2A9 G844A and SLC22A12 C246T variants on serum uric
      acid concentrations in children.
AB  - BACKGROUND: We evaluated the effects of two single-nucleotide polymorphisms on UA
      concentrations in the first decade of life using repeated-measures data. METHODS:
      We included all subjects who were followed-up at least once and for whom we had
      both UA and genotypic data (i.e., 375, 204, 307, and 363 patients aged 3, 5, 7,
      and 9 years, respectively). All participated in the Ewha Birth and Growth Cohort
      study. We used a mixed model analysis to estimate the longitudinal association of
      serum UA concentration due to the rs3825017 (SLC22A12 c. 246C > T) and rs16890979
      (SLC2A9 c. 844G > A) genotypes. RESULTS: Overall, the tracking coefficient of UA
      concentrations in children 3 to 9 years of age was 0.31, and was higher in boys
      than in girls (0.34 vs. 0.29, respectively). Regarding individual variance, serum
      UA concentrations decreased as age increased (beta = - 0.07, p < 0.05), but there
      were no significant differences by sex. The effects of rs3825017 on UA
      concentration were significant in boys, but not in girls. Boys with the T allele
      of rs3825017 had higher concentrations than their counterparts regardless of the
      time of follow-up. The rs16890979 genotypes were not significantly associated
      with serum UA concentration in either sex. CONCLUSION: This study showed that
      rs3825017 in the SLC22A12 gene was associated with UA concentration in childhood.

PMID- 30189836
TI  - Prioritizing candidate genes post-GWAS using multiple sources of data for
      mastitis resistance in dairy cattle.
AB  - BACKGROUND: Improving resistance to mastitis, one of the costliest diseases in
      dairy production, has become an important objective in dairy cattle breeding.
      However, mastitis resistance is influenced by many genes involved in multiple
      processes, including the response to infection, inflammation, and post-infection
      healing. Low genetic heritability, environmental variations, and farm management
      differences further complicate the identification of links between genetic
      variants and mastitis resistance. Consequently, studies of the genetics of
      variation in mastitis resistance in dairy cattle lack agreement about the
      responsible genes. RESULTS: We associated 15,552,968 imputed whole-genome
      sequencing markers for 5147 Nordic Holstein cattle with mastitis resistance in a
      genome-wide association study (GWAS). Next, we augmented P-values for markers in
      genes in the associated regions using Gene Ontology terms, Kyoto Encyclopedia of
      Genes and Genomes pathway analysis, and mammalian phenotype database. To confirm
      results of gene-based analyses, we used gene expression data from E. coli
      challenged cow udders. We identified 22 independent quantitative trait loci (QTL)
      that collectively explained 14% of the variance in breeding values for resistance
      to clinical mastitis (CM). Using association test statistics with multiple pieces
      of independent information on gene function and differential expression during
      bacterial infection, we suggested putative causal genes with biological relevance
      for 12 QTL affecting resistance to CM in dairy cattle. CONCLUSION: Combining
      information on the nearest positional genes, gene-based analyses, and
      differential gene expression data from RNA-seq, we identified putative causal
      genes (candidate genes with biological evidence) in QTL for mastitis resistance
      in Nordic Holstein cattle. The same strategy can be applied for other traits.

PMID- 30189837
TI  - Decreased methylation in the SNAI2 and ADAM23 genes associated with de
      differentiation and haematogenous dissemination in breast cancers.
AB  - BACKGROUND: In breast cancer (BC), deregulation of DNA methylation leads to
      aberrant expressions and functions of key regulatory genes. In our study, we
      investigated the relationship between the methylation profiles of genes
      associated with cancer invasivity and clinico-pathological parameters. In detail,
      we studied differences in the methylation levels between BC patients with
      haematogenous and lymphogenous cancer dissemination. METHODS: We analysed samples
      of primary tumours (PTs), lymph node metastases (LNMs) and peripheral blood cells
      (PBCs) from 59 patients with sporadic disseminated BC. Evaluation of the DNA
      methylation levels of six genes related to invasivity, ADAM23, uPA, CXCL12,
      TWIST1, SNAI1 and SNAI2, was performed by pyrosequencing. RESULTS: Among the
      cancer-specific methylated genes, we found lower methylation levels of the SNAI2
      gene in histologic grade 3 tumours (OR = 0.61; 95% CI, 0.39-0.97; P = 0.038) than
      in fully or moderately differentiated cancers. We also evaluated the methylation
      profiles in patients with different cancer cell dissemination statuses
      (positivity for circulating tumour cells (CTCs) and/or LNMs). We detected the
      significant association between reduced DNA methylation of ADAM23 in PTs and
      presence of CTCs in the peripheral blood of patients (OR = 0.45; 95% CI, 0.23
      0.90; P = 0.023). CONCLUSION: The relationships between the decreased methylation
      levels of the SNAI2 and ADAM23 genes and cancer de-differentiation and
      haematogenous dissemination, respectively, indicate novel functions of those
      genes in the invasive processes. After experimental validation of the association
      between the lower values of SNAI2 and ADAM23 methylation and clinical features of
      aggressive BCs, these methylation profiles could improve the management of
      metastatic disease.

PMID- 30189838
TI  - Effective normalization for copy number variation in Hi-C data.
AB  - BACKGROUND: Normalization is essential to ensure accurate analysis and proper
      interpretation of sequencing data, and chromosome conformation capture data such
      as Hi-C have particular challenges. Although several methods have been proposed,
      the most widely used type of normalization of Hi-C data usually casts estimation
      of unwanted effects as a matrix balancing problem, relying on the assumption that
      all genomic regions interact equally with each other. RESULTS: In order to
      explore the effect of copy-number variations on Hi-C data normalization, we first
      propose a simulation model that predict the effects of large copy-number changes
      on a diploid Hi-C contact map. We then show that the standard approaches relying
      on equal visibility fail to correct for unwanted effects in the presence of copy
      number variations. We thus propose a simple extension to matrix balancing methods
      that model these effects. Our approach can either retain the copy-number
      variation effects (LOIC) or remove them (CAIC). We show that this leads to better
      downstream analysis of the three-dimensional organization of rearranged genomes.
      CONCLUSIONS: Taken together, our results highlight the importance of using
      dedicated methods for the analysis of Hi-C cancer data. Both CAIC and LOIC
      methods perform well on simulated and real Hi-C data sets, each fulfilling
      different needs.

PMID- 30189839
TI  - Is being a "small fish in a big pond" bad for students' psychosomatic health? A
      multilevel study on the role of class-level school performance.
AB  - BACKGROUND: Features of schools and classes are closely related to students'
      health and wellbeing. However, class composition (e.g. in terms of school
      performance) has rarely been examined in relation to students' health and
      wellbeing. This study focuses on the so called Big-Fish-Little-Pond-Effect
      (BFLPE), by investigating whether the level of high-performing students in
      classroom is negatively associated with psychosomatic complaints of students who
      perceive themselves as poor performers. METHODS: Data were derived from the
      German sample of the WHO-Collaborative "Health Behaviour in School-aged Children
      (HBSC)" study 2013/2014. The sample included 5226 11-, 13- and 15-year-old
      students. Individual perceived school performance (PSP) was included (very
      good/good vs. average/below average PSP) at the individual student-level. At the
      class-level, school performance in class was generated by aggregating the share
      (in percentage) of students who report a very good/good PSP to the class-level,
      indicating the percentage of students with good/very good PSP in classroom. Using
      multilevel regression models, the association between class-level school
      performance (in percentage of students with very good/good PSP) and individual
      psychosomatic complaints were analyzed, stratified by students' individual PSP.
      RESULTS: Students who report average/below average PSP showed higher likelihoods
      of psychosomatic complaints (Odds Ratio: 1.75; 95% Confidence Interval: 1.52
      2.03) compared to counterparts with very good/good PSP. The aggregated class
      level PSP was not significantly associated with psychosomatic complaints.
      However, in line with the BFLPE, results further revealed that students with
      average/below average PSP, who attend classes with a higher percentage of
      students who report very good/good PSP, had higher likelihoods of psychosomatic
      complaints (Odds Ratio: 1.91; 95% Confidence Interval: 1.01-4.01) compared to
      classmates with very good/good PSP. CONCLUSIONS: This study revealed that class
      composition in terms of PSP was differentially associated with students'
      psychosomatic complaints, depending on their individual PSP. Findings highlight
      the vulnerability of students with poor PSP placed in classes with a higher
      percentage of students with good PSP. Results of this study therefore indicate a
      need for initiatives for low performing students from teachers and school staff
      in class.

PMID- 30189840
TI  - Topical steroid versus placebo for the prevention of radiation dermatitis in head
      and neck cancer patients receiving chemoradiotherapy: the study protocol of J
      SUPPORT 1602 (TOPICS study), a randomized double-blinded phase 3 trial.
AB  - BACKGROUND: To date, the clinical benefit of topical steroid use has only been
      demonstrated for radiation dermatitis induced by 50-60 Gy irradiation in breast
      cancer. However, these agents are also often used clinically for the control of
      radiation dermatitis induced by high-dose (>60Gy) irradiation with chemotherapy
      in head and neck cancer. Despite this, the prophylactic efficacy of topical
      steroids for radiation dermatitis induced by high-dose irradiation is still
      unclear. The aim of this study is to clarify the benefit of topical steroids in
      basic nursing care for radiation dermatitis induced by chemoradiotherapy in
      patients with head and neck cancer. METHODS: The study is being conducted as a
      multicenter 2-arm randomized double-blinded placebo-controlled Phase 3 trial in
      Japan. The study was started in May 2017, with participant enrollment between May
      2017 and April 2019. Patients scheduled to receive definitive or postoperative
      chemoradiotherapy for head and neck cancer are eligible for enrollment. All
      patients will receive chemoradiotherapy, consisting of single agent CDDP and 70
      Gy irradiation. Bilateral neck irradiation is mandatory. Supportive care for
      radiation dermatitis will consist of basic nursing care with topical steroid or
      placebo. When radiation dermatitis grade 1 is seen or total radiation dose
      reaches 30 Gy, minimally required intervention will be started as a first step.
      If radiation dermatitis worsens to grade 2, the irradiated area will be covered
      with a moderately absorbent surgical pad and steroid or placebo topical cream.
      The primary endpoint is a comparison of the proportion of patients with >= grade
      2 radiation dermatitis by NCI Common Terminology Criteria for Adverse Events
      (CTCAE) Version 4.0. Ethical approval has been obtained from all participating
      sites. The results of this study will be submitted for publication in
      international peer-reviewed journals and the key findings will be presented at
      international scientific conferences. DISCUSSION: Evidence supporting the benefit
      of adding topical steroids in general nursing care for radiation dermatitis
      induced by high-dose irradiation with chemotherapy is insufficient. This trial
      aims to clarify the clinical benefit of topical steroid for radiation dermatitis
      induced by high-dose irradiation with chemotherapy. The trial is ongoing and is
      currently recruiting. TRIAL REGISTRATION NUMBER: UMIN000027161 . Protocol version
      3.0, 18 April 2017.

PMID- 30189841
TI  - Factors associated with hospitalization after self-poisoning in France: special
      focus on the impact of alcohol use disorder.
AB  - BACKGROUND: Previous studies have identified factors associated with admission to
      hospital after suicide spectrum behaviors. In this study, we aim to identify
      specific factors associated with psychiatric hospitalization after self
      poisoning. Given earlier findings suggesting that alcohol use disorder is not
      associated with hospital admission, we also aim to consider its impact, as well
      as blood alcohol concentrations, on hospitalization decisions after a suicide
      attempt. METHODS: We studied the association between demographic features,
      suicide intent, psychiatric characteristics and admission to hospital in self
      poisoning patients in an emergency department in France. RESULTS: Suicide intent,
      a past history of suicide attempts, bipolar disorder and depression were
      associated with psychiatric hospital admissions. Despite alcohol use disorder
      being known to be associated with a suicide risk, it was not linked with
      psychiatric hospitalization. A positive blood alcohol concentration in the
      emergency department likewise had no association with admission to a psychiatric
      ward for inpatient care. CONCLUSIONS: Our findings were similar to those reported
      for other suicide spectrum behaviors. Alcohol use disorder was not associated
      with admission for inpatient psychiatric care, whereas depression clearly was.
      The cause of this discrepancy must be determined in future research.

PMID- 30189842
TI  - Timely initiation of postpartum contraceptive utilization and associated factors
      among women of child bearing age in Aroressa District, Southern Ethiopia: a
      community based cross-sectional study.
AB  - BACKGROUND: Globally, more than 90% of women during the first year of postpartum
      period want to either delay or avoid future pregnancies. The first year
      postpartum period is more crucial time to use modern contraceptives that enhance
      maternal and child health, so more attention should be given on time of
      initiating modern contraceptive utilization after delivery. Therefore, the aim of
      this study was to assess the magnitude and associated factors of timely
      initiation of postpartum contraceptive utilization among women of child bearing
      age in Aroressa district, Southern Ethiopia. METHODS: The study was conducted in
      Aroressa district from March 15 to April 15, 2017. A community based cross
      sectional study design with interviewer administered structured and pretested
      questionnaire was used. Multistage sampling technique was employed involving a
      total of 695 women of child bearing age who delivered a child in the past 12
      months prior to the study period. Data were cleaned, coded and entered into Epi
      data version 3.1, then exported to statistical package for social science version
      20 for analysis. Descriptive statistics, Bivariate and Multivariate logistic
      regression analysis were done. p-value < 0.05 was used to consider significant
      variables. RESULTS: The magnitude of timely initiation of postpartum
      contraceptive utilization was found to be 31.7% [95% CI (28, 36)]. Antenatal care
      [AOR = 1.94, 95% CI (1.23, 3.01)], postnatal care [AOR = 1.90, 95%CI (1.23,
      2.94)], spousal communication on contraceptive methods [AOR = 1.63, 95% CI (1.09,
      2.41)] and resumption of menses after delivery [AOR = 2.6, 95% CI (1.47, 3.81)]
      were predictors positively associated with timely initiation of postpartum
      contraceptive utilization. CONCLUSION: The magnitude of timely initiation of
      postpartum contraceptive utilization was low. Strengthening integration of family
      planning information with antenatal and postnatal care follow up and encouraging
      spousal communication by promoting information, education and communication
      activities is important to enhance contraceptive use on timely manner.

PMID- 30189843
TI  - Nucleus- and plastid-targeted annexin 5 promotes reproductive development in
      Arabidopsis and is essential for pollen and embryo formation.
AB  - BACKGROUND: Pollen development is a strictly controlled post-meiotic process
      during which microspores differentiate into microgametophytes and profound
      structural and functional changes occur in organelles. Annexin 5 is a calcium-
      and lipid-binding protein that is highly expressed in pollen grains and regulates
      pollen development and physiology. To gain further insights into the role of ANN5
      in Arabidopsis development, we performed detailed phenotypic characterization of
      Arabidopsis plants with modified ANN5 levels. In addition, interaction partners
      and subcellular localization of ANN5 were analyzed to investigate potential
      functions of ANN5 at cellular level. RESULTS: Here, we report that RNAi-mediated
      suppression of ANN5 results in formation of smaller pollen grains, enhanced
      pollen lethality, and delayed pollen tube growth. ANN5 RNAi knockdown plants also
      displayed aberrant development during the transition from the vegetative to
      generative phase and during embryogenesis, reflected by delayed bolting time and
      reduced embryo size, respectively. At the subcellular level, ANN5 was delivered
      to the nucleus, nucleolus, and cytoplasm, and was frequently localized in plastid
      nucleoids, suggesting a likely role in interorganellar communication.
      Furthermore, ANN5-YFP co-immunoprecipitated with RABE1b, a putative GTPase, and
      interaction in planta was confirmed in plastidial nucleoids using FLIM-FRET
      analysis. CONCLUSIONS: Our findings let us to propose that ANN5 influences basal
      cell homeostasis via modulation of plastid activity during pollen maturation. We
      hypothesize that the role of ANN5 is to orchestrate the plastidial and nuclear
      genome activities via protein-protein interactions however not only in maturing
      pollen but also during the transition from the vegetative to the generative
      growth and seed development.

PMID- 30189844
TI  - Cytosolic GAPDH as a redox-dependent regulator of energy metabolism.
AB  - BACKGROUND: Plant cytosolic NAD-dependent glyceraldehyde-3-phosphate
      dehydrogenase (GapC) displays redox-dependent changes in its subcellular
      localizations and activity. Apart from its fundamental role in glycolysis, it
      also exhibits moonlighting properties. Since the exceptional redox-sensitivity of
      GapC has been suggested to play a crucial role in its various functions, we here
      studied its redox-dependent subcellular localization and the influence of the
      redox-state on GapC protein interactions. RESULTS: In mesophyll protoplasts from
      Arabidopsis thaliana, colocalization of GapC with mitochondria was more
      pronounced under reducing conditions than upon oxidative stress. In accordance,
      reduced GapC showed an increased affinity to the mitochondrial voltage-dependent
      anion-selective channel (VDAC) compared to the oxidized one. On the other hand,
      nuclear localization of GapC was increased under oxidizing conditions. The
      essential role of the catalytic cysteine for nuclear translocation was shown by
      using the corresponding cysteine mutants. Furthermore, interaction of GapC with
      the thioredoxin Trx-h3 as a candidate to revert the redox-modifications, occurred
      in the nucleus of oxidized protoplasts. In a yeast complementation assay, we
      could demonstrate that the plant-specific non-phosphorylating glyceraldehyde 3-P
      dehydrogenase (GapN) can substitute for glucose 6-P dehydrogenase to generate
      NADPH for re-reduction of the Trx system and ROS defense. CONCLUSIONS: The
      preferred association of reduced, glycolytically active GapC with VDAC suggests a
      substrate-channeling metabolon at the mitochondrial surface for efficient energy
      generation. Increased occurrence of oxidized GapC in the nucleus points to a
      function in signal transduction and gene expression. Furthermore, the interaction
      of GapC with Trx-h3 in the nucleus indicates reversal of the oxidative cysteine
      modification after re-establishment of cellular homeostasis. Both, energy
      metabolism and signal transfer for long-term adjustment and protection from redox
      imbalances are mediated by the various functions of GapC. The molecular
      properties of GapC as a redox-switch are key to its multiple roles in
      orchestrating energy metabolism.

PMID- 30189845
TI  - Genome-wide identification and characterization of LRR-RLKs reveal functional
      conservation of the SIF subfamily in cotton (Gossypium hirsutum).
AB  - BACKGROUND: As one of the largest subfamilies of the receptor-like protein
      kinases (RLKs) in plants, Leucine Rich Repeats-RLKs (LRR-RLKs) are involved in
      many critical biological processes including growth, development and stress
      responses in addition to various physiological roles. Arabidopsis contains 234
      LRR-RLKs, and four members of Stress Induced Factor (SIF) subfamily (AtSIF1
      AtSIF4) which are involved in abiotic and biotic stress responses. Herein, we
      aimed at identification and functional characterization of SIF subfamily in
      cultivated tetraploid cotton Gossypium hirsutum. RESULTS: Genome-wide analysis of
      cotton LRR-RLK gene family identified 543 members and phylogenetic analysis led
      to the identification of 6 cotton LRR-RLKs with high homology to Arabidopsis
      SIFs. Of the six SIF homologs, GhSIF1 is highly conserved exhibiting 46-47% of
      homology with AtSIF subfamily in amino acid sequence. The GhSIF1 was transiently
      silenced using Virus-Induced Gene Silencing system specifically targeting the 3'
      Untranslated Region. The transiently silenced cotton seedlings showed enhanced
      salt tolerance compared to the control plants. Further, the transiently silenced
      plants showed better growth, lower electrolyte leakage, and higher chlorophyll
      and biomass contents. CONCLUSIONS: Overall, 543 LRR-RLK genes were identified
      using genome-wide analysis in cultivated tetraploid cotton G. hirsutum. The
      present investigation also demonstrated the conserved salt tolerance function of
      SIF family member in cotton. The GhSIF1 gene can be knocked out using genome
      editing technologies to improve salt tolerance in cotton.

PMID- 30189846
TI  - Impact of a nurse-based intervention on medication outcomes in vulnerable older
      adults.
AB  - BACKGROUND: Medication-related problems are common in older adults with multiple
      chronic conditions. We evaluated the impact of a nurse-based primary care
      intervention, based on the Guided Care model of care, on patient-centered aspects
      of medication use. METHODS: Controlled clinical trial of the Comprehensive Care
      for Multimorbid Adults Project (CC-MAP), conducted among 1218 participants in 7
      intervention clinics and 6 control (usual care) clinics. Inclusion criteria
      included age 45-94, presence of >=3 chronic conditions, and Adjusted Clinical
      Groups (ACG) score > 0.19. The co-primary outcomes were number of changes to the
      medication regimen between baseline and 9 month followup, and number of changes
      to symptom-focused medications, markers of attentiveness to medication-related
      issues. RESULTS: Mean age in the intervention group was 72 years, 59% were women,
      and participants used a mean of 6.6 medications at baseline. The control group
      was slightly older (73 years) and used more medications (mean 7.1). Between
      baseline and 9 months, intervention subjects had more changes to their medication
      regimen than control subjects (mean 4.04 vs. 3.62 medication changes; adjusted
      difference 0.55, p = 0.001). Similarly, intervention subjects had more changes to
      their symptomatic medications (mean 1.38 vs. 1.26 changes, adjusted difference
      0.20, p = 0.003). The total number of medications in use remained stable between
      baseline and follow-up in both groups (p > 0.18). CONCLUSION: This nurse-based,
      primary care intervention resulted in substantially more changes to patients'
      medication regimens than usual care, without increasing the total number of
      medications used. This enhanced rate of change likely reflects greater
      attentiveness to the medication-related needs of patients. TRIAL REGISTRATION:
      This trial is registered at https://clinicaltrials.gov , trial number NCT01811173
      .

PMID- 30189847
TI  - Determinants of fertility issues experienced by young women diagnosed with breast
      or gynaecological cancer - a quantitative, cross-cultural study.
AB  - BACKGROUND: Although there is a recognition of the importance of fertility to
      young women with cancer, we do not know who is at risk of distress related to
      fertility issues following diagnosis. We investigated the determinants of
      fertility-related distress adopting a cross-cultural perspective and using the
      Common Sense Model (CSM). We chose the CSM as a theoretical framework as it
      allows to explore how individuals conceptualise illness within the socio-cultural
      context. METHODS: British and Polish women with breast or gynaecological cancer
      were recruited through outpatient clinics or online outlets and completed a
      questionnaire. Linear regression, mediation and moderated mediation methods were
      performed. RESULTS: One hundred sixty-four women participated (mean age 34.55 (SD
      = 6.66); 78.7% had gynaecological cancer). The determinants of fertility-related
      distress were: country of origin, recruitment site, negative affect, desire to
      have children, treatment regret, and total illness perception score. The impact
      of the desire to have children on fertility-related distress was mediated by
      psychological value of children, perceived consequences of cancer on one's life,
      emotional representation, and treatment-related regret. Country of origin
      moderated the relationship between the desire to have children and fertility
      related distress when mediated by treatment-related regret. CONCLUSIONS: The CSM
      proved useful in investigating predictors of fertility-related distress, with
      emotional, rather than cognitive representation of illness determining its
      levels. Socio-cultural background played a role in determining one's fertility
      related distress and contributed to the explanation of the relationship between
      one's desire to have children, treatment-related regret, and fertility-related
      distress.

PMID- 30189849
TI  - Mother-infant interaction quality and sense of parenting competence at six months
      postpartum for first-time mothers in Taiwan: a multiple time series design.
AB  - BACKGROUND: For first-time mothers, not knowing how to interact with newborn
      infants increases anxiety and decreases the quality of the parent-infant
      interactions. A substantial lack of interactional knowledge can ultimately limit
      the adjustments necessary for a stable transition into motherhood. This study
      investigated how postpartum parenting education influenced first-time mothers'
      mother-infant interaction quality and parenting sense of competence. METHODS:
      Eighty-one healthy first-time-mother and infant dyads were recruited. The control
      group (n = 40) received postpartum care based on the medical and cultural norms
      practiced in Taiwan, while the experimental group (n = 41) received, on top of
      typical care, education by way of a 40-min videotape on infant states, behaviors,
      and communication cues, as well as a handout on play practices. Data were
      collected at five points: within the first week, and during follow-ups in the
      first, second, third, and sixth months after birth. We administered the Chinese
      versions of the Parenting Sense of Competence Scale and Edinburgh Perinatal
      Depression Scale, and used the Nursing Child Assessment Teaching Scale to score
      videotaped mother-infant interactions. RESULTS: We observed an increase in the
      quality of mother-infant interaction within the experimental group only.
      Furthermore, at the five assessment points, we observed no significant changes in
      perceived parenting competence. Among all subjects, there were correlations
      between postpartum depression scores, parenting competency, and quality of mother
      infant interaction. CONCLUSIONS: Our results indicate that first-time mothers in
      Taiwan who are provided with extra education on infants' abilities and how to
      effectively play with infants are likely to exhibit improvements in quality of
      interaction.

PMID- 30189850
TI  - The roles of aromatic residues in the glycine receptor transmembrane domain.
AB  - BACKGROUND: Cys-loop receptors play important roles in fast neuronal signal
      transmission. Functional receptors are pentamers, with each subunit having an
      extracellular, transmembrane (TM) and intracellular domain. Each TM domain
      contains 4 alpha-helices (M1-M4) joined by loops of varying lengths. Many of the
      amino acid residues that constitute these alpha-helices are hydrophobic, and
      there has been particular interest in aromatic residues, especially those in M4,
      which have the potential to contribute to the assembly and function of the
      receptor via a range of interactions with nearby residues. RESULTS: Here we show
      that many aromatic residues in the M1, M3 and M4 alpha-helices of the glycine
      receptor are involved in the function of the receptor. The residues were explored
      by creating a range of mutant receptors, characterising them using two electrode
      voltage clamp in Xenopus oocytes, and interpreting changes in receptor parameters
      using currently available structural information on the open and closed states of
      the receptor. For 7 residues function was ablated with an Ala substitution: 3 Tyr
      residues at the extracellular end of M1, 2 Trp residues located towards the
      centers of M1 and M3, and a Phe and a Tyr residue in M4. For many of these an
      alternative aromatic residue restored wild-type-like function indicating the
      importance of the pi ring. EC50s were increased with Ala substitution of 8 other
      aromatic residues, with those in M1 and M4 also having reduced currents,
      indicating a role in receptor assembly. The structure shows many potential
      interactions with nearby residues, especially between those that form the
      M1/M3/M4 interface, and we identify those that are supported by the functional
      data. CONCLUSION: The data reveal the importance and interactions of aromatic
      residues in the GlyR M1, M3 and M4 alpha-helices, many of which are essential for
      receptor function.

PMID- 30189848
TI  - Jasmonate promotes auxin-induced adventitious rooting in dark-grown Arabidopsis
      thaliana seedlings and stem thin cell layers by a cross-talk with ethylene
      signalling and a modulation of xylogenesis.
AB  - BACKGROUND: Adventitious roots (ARs) are often necessary for plant survival, and
      essential for successful micropropagation. In Arabidopsis thaliana dark-grown
      seedlings AR-formation occurs from the hypocotyl and is enhanced by application
      of indole-3-butyric acid (IBA) combined with kinetin (Kin). The same IBA + Kin
      treatment induces AR-formation in thin cell layers (TCLs). Auxin is the main
      inducer of AR-formation and xylogenesis in numerous species and experimental
      systems. Xylogenesis is competitive to AR-formation in Arabidopsis hypocotyls and
      TCLs. Jasmonates (JAs) negatively affect AR-formation in de-etiolated Arabidopsis
      seedlings, but positively affect both AR-formation and xylogenesis in tobacco
      dark-grown IBA + Kin TCLs. In Arabidopsis the interplay between JAs and auxin in
      AR-formation vs xylogenesis needs investigation. In de-etiolated Arabidopsis
      seedlings, the Auxin Response Factors ARF6 and ARF8 positively regulate AR
      formation and ARF17 negatively affects the process, but their role in xylogenesis
      is unknown. The cross-talk between auxin and ethylene (ET) is also important for
      AR-formation and xylogenesis, occurring through EIN3/EIL1 signalling pathway.
      EIN3/EIL1 is the direct link for JA and ET-signalling. The research investigated
      JA role on AR-formation and xylogenesis in Arabidopsis dark-grown seedlings and
      TCLs, and the relationship with ET and auxin. The JA-donor methyl-jasmonate
      (MeJA), and/or the ET precursor 1-aminocyclopropane-1-carboxylic acid were
      applied, and the response of mutants in JA-synthesis and -signalling, and ET
      signalling investigated. Endogenous levels of auxin, JA and JA-related compounds,
      and ARF6, ARF8 and ARF17 expression were monitored. RESULTS: MeJA, at 0.01 MUM,
      enhances AR-formation, when combined with IBA + Kin, and the response of the
      early-JA-biosynthesis mutant dde2-2 and the JA-signalling mutant coi1-16
      confirmed this result. JA levels early change during TCL-culture, and JA/JA-Ile
      is immunolocalized in AR-tips and xylogenic cells. The high AR-response of the
      late JA-biosynthesis mutant opr3 suggests a positive action also of 12
      oxophytodienoic acid on AR-formation. The crosstalk between JA and ET-signalling
      by EIN3/EIL1 is critical for AR-formation, and involves a competitive modulation
      of xylogenesis. Xylogenesis is enhanced by a MeJA concentration repressing AR
      formation, and is positively related to ARF17 expression. CONCLUSIONS: The JA
      concentration-dependent role on AR-formation and xylogenesis, and the interaction
      with ET opens the way to applications in the micropropagation of recalcitrant
      species.

PMID- 30189851
TI  - An integrated strategy for identifying new targets and inferring the mechanism of
      action: taking rhein as an example.
AB  - BACKGROUND: Target identification is necessary for the comprehensive inference of
      the mechanism of action of a compound. The application of computational methods
      to predict the targets of bioactive compounds saves cost and time in drug
      research and development. Therefore, we designed an integrated strategy
      consisting of ligand-protein docking, network analysis, enrichment analysis, and
      an experimental surface plasmon resonance (SPR) method to identify and validate
      new targets, and then used enriched pathways to elucidate the underlying
      pharmacological mechanisms. Here, we used rhein, a compound with various
      pharmacological activities, as an example to find some of its previously unknown
      targets and to determine its pharmacological activity. RESULTS: A total of nine
      candidate targets were discovered, including LCK, HSP90AA1, RAB5A, EGFR, CDK2,
      CDK6, GSK3B, p38, and JNK. LCK was confirmed through SPR experiments, and
      HSP90AA1, EGFR, CDK6, p38, and JNK were validated through previous reports. Rhein
      network regulations are complex and interconnected. The therapeutic effect of
      rhein is the synergistic and comprehensive result of this vast and complex
      network, and the perturbation of multiple targets gives rhein its various
      pharmacological activities. CONCLUSIONS: This study provided a new integrated
      strategy to identify new targets of bioactive compounds and reveal their
      molecular mechanisms of action.

PMID- 30189852
TI  - Involvement of Akt/CREB signaling pathways in the protective effect of EPA
      against interleukin-1beta-induced cytotoxicity and BDNF down-regulation in
      cultured rat hippocampal neurons.
AB  - BACKGROUND: Our published data have indicated that the omega-3 polyunsaturated
      fatty acid eicosapentaenoic acid (EPA) provides beneficial effects by attenuating
      neuronal damage induced by interleukin-1beta (IL-1beta), and up-regulation of the
      expression of brain-derived neurotrophic factor (BDNF) represents a crucial part
      in the neuroprotective effect of EPA. However, the mechanisms of how EPA
      regulates BDNF expression remains incompletely understood. The present study
      investigated the role of Akt/CREB signaling in the effect of EPA on BDNF
      expression and its neuroprotective effect. RESULTS: The present results showed
      that IL-1beta reduced hippocampal neuronal viability and that EPA showed a
      concentration-dependent neuroprotective effect, but the neuroprotective effects
      of EPA were abolished by inhibition of Akt using KRX-0401, an inhibitor of Akt.
      Treatment of hippocampal neurons with EPA also ameliorated the decrease in Akt
      and CREB phosphorylation induced by IL-1beta and BDNF down-regulation mediated by
      IL-1beta. However, inhibition of Akt reversed the effect of EPA on levels of p
      Akt, p-CREB, and BDNF. CONCLUSIONS: Our data indicate that EPA elicited
      neuroprotection toward IL-1beta-induced cell damage and BDNF decrease and that
      its effects potentially occurred via the Akt/CREB signaling pathway.

PMID- 30189853
TI  - Rheumatoid meningitis presenting with a stroke-like attack treated with
      recombinant tissue plasminogen activator: a case presentation.
AB  - BACKGROUND: Rheumatoid meningitis presenting with a stroke-like attack (RMSA) is
      a rare manifestation of rheumatoid arthritis (RA). When the patients arrive
      within the time-window for recombinant tissue plasminogen activator (rt-PA)
      infusion therapy, no diagnostic protocol has been established. CASE PRESENTATION:
      A 55-year-old woman was brought by ambulance to our hospital with complaints of
      sudden-onset dysarthria and left arm numbness. The National Institutes of Health
      Stroke Scale (NIHSS) score was 5, and the Alberta Stroke Program Early CT Score
      was 8. She was diagnosed with acute embolic stroke. At 4 h, 6 min after onset,
      intravenous administration of rt-PA (alteplase, 0.6 mg/kg) was started. Her
      neurological deficits improved rapidly, and her NIHSS score was 1. Brain MRI was
      then performed. There was no hemorrhagic transformation, but the MRI findings
      were not compatible with ischemic stroke. She had a past history of RA diagnosed
      6 months earlier, and she had been treated with methotrexate (10 mg daily). She
      was diagnosed with RMSA, and continuous infusion of methylprednisolone 1000 mg
      daily was started for 3 days. The high signal intensity on the FLAIR image
      disappeared. CONCLUSION: CT-based decision-making for rt-PA injection is
      reasonable, but MRI is needed for the early diagnosis of RMSA. In this case, it
      is particularly important that neither adverse events nor bleeding complications
      were observed, suggesting the safety of CT-based thrombolytic therapy in RMSA.

PMID- 30189854
TI  - The long-term rate of change in lung function in urban professional firefighters:
      a systematic review.
AB  - BACKGROUND: Despite the known occupational hazards, it is not yet clear whether
      long-term career firefighting leads to a greater rate of decline in lung function
      than would normally be expected, and how this rate of change is affected by
      firefighting exposures and other risk/protective factors. METHODS: A systematic
      search of online electronic databases was conducted to identify longitudinal
      studies reporting on the rate of change in the forced expiratory volume in one
      second (FEV1) of forced vital capacity (FVC). Included studies were critically
      appraised to determine their risk of bias using the Research Triangle Institute
      Item Bank (RTI-IB) on Risk of Bias and Precision of Observational Studies.
      RESULTS: Twenty-two studies were identified for inclusion, from four different
      countries, published between 1974 and 2016. Examined separately, studies were
      categorised by the type of firefighting exposure. Firefighters experienced
      variable rates of decline in lung function, which were particularly influenced by
      cigarette smoking. The influence of routine firefighting exposures is unclear and
      limited by the methods of measurement, while firefighters exposed to 'non
      routine' severe exposures unanimously experienced accelerated declines.
      CONCLUSIONS: The data provided by longitudinal studies provide an unclear picture
      of how the rate of change in lung function of firefighters relates to routine
      exposures and how it compares to the rate of change expected in a working-age
      population. Non-smoking firefighters who routinely wear respiratory protection
      are more likely than otherwise to have a normal rate of decline in lung function.
      Exposure to catastrophic events significantly increases the rate of decline in
      firefighter lung function but there is limited evidence detailing the effect of
      routine firefighting. Future studies will benefit from more robust methods of
      measuring exposure. TRIAL REGISTRATION: International Prospective Register of
      Systematic Reviews (PROSPERO), registration number ( CRD42017058499 ).

PMID- 30189855
TI  - Fidelity of HIV programme implementation by community health workers in rural
      Mopani district, South Africa: a community survey.
AB  - BACKGROUND: South Africa has implemented a community health programme delivered
      by community health workers (CHWs) to strengthen primary healthcare services.
      Provision of community Human Immunodeficiency Virus (HIV) services constitutes an
      important component of this programme. To support effectiveness, we assessed
      fidelity of HIV programme implementation by CHWs from the community's perspective
      in a rural South African setting. METHODS: A cross-sectional study was conducted
      targeting 900 randomly selected households in twelve wards of two sub-districts
      (Greater Giyani and Greater Letaba) of Mopani District (Limpopo Province, South
      Africa). Questionnaires were administered to the traditionally most appropriate
      adult member of the household. Included were questions related to the four
      standard components to measure implementation fidelity against local guidelines:
      coverage, frequency, duration and content of HIV programme implementation.
      RESULTS: Participants were enrolled at 534 households; in most other cases there
      was nobody or no adult member at home (n = 291). Reported coverage of 55%
      (141/253) and a frequency of 47% (66/140) were higher in Greater Giyani as
      compared to Greater Letaba (44%; 122/278 and 29%; 33/112, respectively, p = 0.007
      for both comparisons). Coverage was not associated with the distance from the
      participant's household to the facility (p = 0.93). Duration of programme
      delivery was reported to be high, where all CHW visits (253/253; 100%) were
      conducted within the last 6 months and the content delivered was adequate
      (242/253; 96%). Individuals reporting a CHW visit were more likely to know their
      HIV status than those not visited (OR = 2.0; 95% CI 1.06-3.8; p = 0.032). Among
      those visited by the CHW discussion of HIV was associated with knowing the HIV
      status (OR = 2.2; 95% CI 1.02-4.6; p = 0.044); in particular for women (OR = 2.9;
      95% CI 1.5-5.4; p = 0.001). CONCLUSIONS: This study demonstrates promising HIV
      programme implementation fidelity by CHWs in rural South Africa. Programme
      coverage and frequency should be improved whilst maintaining the good levels of
      duration and content. Resource investment, strengthening of operational
      structure, and research to identify other facilitators of programme
      implementation are warranted to improve programme effectiveness and impact.

PMID- 30189856
TI  - Phylogeographic pattern of the plane leaf miner, Phyllonorycter platani
      (STAUDINGER, 1870) (Lepidoptera: Gracillariidae) in Europe.
AB  - BACKGROUND: The plane leaf miner, Phyllonorycter platani is a widely distributed
      insect species on plane trees and has a well-documented colonisation history in
      Europe over the last century. However, phylogeographic data of the species are
      lacking. RESULTS: We analysed 284 individuals from 38 populations across Europe,
      Asia, and North America. A 1242 bp fragment of the mitochondrial COI gene and an
      893 bp fragment of the 28S rDNA has been Sanger sequenced. Twenty-four haplotypes
      were detected on the COI gene, and two alleles were identified on the 28S rDNA.
      We revealed two distinct clades for both markers reflecting the geographic
      origins, Asia and Europe. The genetic distance between the two main clades is
      2.08% on the COI gene and 0.10% on the nuclear DNA. An overlapping zone of the
      two clades was found across Eastern Europe and the Anatolian Peninsula. We
      detected heterozygote individuals of the 28S rDNA gene in Moldavia, Ukraine and
      in the southern part of Turkey. These suggest that the two clades can hybridise.
      Furthermore, the presence of European type homozygote individuals has been
      confirmed in the southern part of Turkey as well. CONCLUSIONS: We have shown that
      both post-glacial recolonization and recent expansion events influenced the
      present genetic structure of P. platani. The genetic patterns revealed at least
      two refugia during the last ice age: one in the Balkan Peninsula and the other in
      the Caucasus region. Recent expansion was detected in some European and Central
      Asian populations. The two main clades (Europe/Asia) show definite genetic
      differences; however, several hybrid individuals were found in the overlapping
      zone as well (stretching over Eastern Europe and the Anatolian Peninsula).
      Discrepancies in mitochondrial and nuclear data indicate introgressions in the
      southern part of the Anatolian Peninsula.

PMID- 30189857
TI  - Prolonged exposure therapy and supportive counselling for posttraumatic stress
      disorder in adolescents in a community-based sample, including experiences of
      stakeholders: study protocol for a comparative randomized controlled trial using
      task-shifting.
AB  - BACKGROUND: There is a dearth of empirical evidence on the effectiveness of
      pharmacological and non-pharmacological treatments for adolescents with
      posttraumatic stress disorder (PTSD) in developing countries. The primary aim of
      the study is to examine the effects of prolonged exposure therapy compared with
      supportive counseling for adolescents with PTSD delivered by nurses trained as
      counselors. METHODS/DESIGN: A single-blind randomized clinical trial comprising
      90 adolescents with PTSD using a permuted block design will be utilized. Nurses
      previously naive to prolonged exposure and supportive counselling will be trained
      to provide these treatments at the adolescents' high schools. Data collection
      will last from March 2014 to December 2017 and annually thereafter, dependent on
      the availability of funding. Participants will receive seven to fourteen 60 min
      sessions of prolonged exposure treatment (n = 45) or supportive counselling (n =
      45). All assessments will be conducted before treatment, at mid-treatment,
      immediately after treatment completion, at 3-, 6-, and 12-month follow-up, and
      annually thereafter. It is hypothesized that PE-A will be superior to SC in
      reducing PTSD symptoms at post-treatment as measured by the CPSS-I administered
      by an independent evaluator. It is further hypothesized that PE-A treatment gains
      will be maintained at 3-, 6- and 12-month follow-ups and annually thereafter.
      DISCUSSION: While early indications are that PE-A is an effective treatment for
      PTSD in adolescents, this study will help determine the effectiveness of PE-A in
      a South African, community setting (school-based) when task-shifted to nurses, as
      compared to SC. TRIAL REGISTRATION: Pan African Clinical Trials Registry:
      PACTR201511001345372 , retrospectively registered 11 November 2015.

PMID- 30189859
TI  - Reliability of a participant-friendly fecal collection method for microbiome
      analyses: a step towards large sample size investigation.
AB  - BACKGROUND: The effects of gut microbiota on human traits are expected to be
      small to moderate and adding the complexity of the human diseases, microbiome
      research demands big sample sizes. Fecal samples for such studies are mostly self
      collected by participants at home. This imposes an extra level of complexity as
      sample collection and storage can be challenging. Effective, low-burden
      collection and storage methods allowing fecal samples to be transported properly
      and ensuring optimal quality and quantity of bacterial DNA for upstream analyses
      are necessary. Moreover, accurate assessment of the microbiome composition also
      depends on bacterial DNA extraction method. The aim of this study was to evaluate
      the reliability and efficiency of the OMNIgene*GUT kit as a participant-fecal
      friendly collection method (storage at room temperature for 24 h (O24h) or 7 days
      (O7d)) in comparison to the standard collection method (Fresh, storage at 4 
      degrees C for less than 24 h) in terms of amount of variability and information
      content accounting for two common DNA extraction methods. RESULTS: Fourteen fecal
      samples were collected from healthy individuals (7 males, 7 females). Collection
      and storage methods did not differ significantly in terms of DNA concentration
      and Shannon diversity index. Phylum relative abundance showed significant
      differences for Bacteroidetes, Actinobacteria and Cyanobacteria. The differences
      were observed between control (Fresh) and O24h methods, but not between Fresh and
      O7d. These differences were not seen when performing bacterial DNA quantification
      based on three bacterial groups: Bacteroides spp., Bifidobacterium spp. and
      Clostridium cluster IV, which represent three major phyla: Bacteroidetes,
      Actinobacteria and Firmicutes respectively. The two DNA extraction methods differ
      in terms of DNA quantity, quality, bacterial diversity and bacterial relative
      abundance. Furthermore, principal component analysis revealed differences in
      microbial structure, which are driven by the DNA extraction methods more than the
      collection/storage methods. CONCLUSION: Our results have highlighted the
      potential of using the OMNIgene*GUT kit for collection and storage at ambient
      temperature, which is convenient for studies aiming to collect large samples by
      giving participants the possibility to send samples by post. Importantly, we
      revealed that the choice of DNA extraction method have an impact on the
      microbiome profiling.

PMID- 30189861
TI  - Elevated contextual fear memory by SIRT6 depletion in excitatory neurons of mouse
      forebrain.
AB  - A class of NAD-dependent protein deacetylases, the Sirtuin (SIRT) family of
      proteins is involved in aging, cell survival, and neurodegeneration. Recently,
      SIRT proteins, including SIRT6, have been reported to be important in learning
      and memory. However, the role of SIRT6 in excitatory brain neurons in cognitive
      behaviors is not well characterized. We investigated how cognitive behaviors are
      affected by genetic SIRT6 depletion in excitatory neurons in the mouse forebrain.
      We generated a conditional knockout (cKO) mouse line by mating two transgenic
      lines, Floxed SIRT6 and CaMKIIa-Cre. SIRT6 was thus deleted by Cre recombinase in
      CaMKIIa-expressing excitatory neurons. We performed cognitive behavioral tests,
      focusing on learning and memory, including contextual fear conditioning and
      Morris-water maze. The freezing level of SIRT6 cKO before the fear conditioning
      was comparable to that of wild-type littermate controls, while the freezing level
      after the conditioning was higher in SIRT6 cKO mice. In contrast, the mice showed
      normal spatial learning and memory in the Morris-water maze. In addition, anxiety
      and locomotion were also normal in SIRT6 cKO mice. SIRT6 genetic depletion
      enhanced contextual fear memory without affecting spatial memory. Since a
      previous report showed that overexpression of SIRT6 reduced contextual fear
      memory, our results suggest that the expression level of SIRT6 bi-directionally
      regulates contextual fear memory in mice.

PMID- 30189858
TI  - Structural and functional brain changes in perimenopausal women who are
      susceptible to migraine: a study protocol of multi-modal MRI trial.
AB  - BACKGROUND: As a common clinical symptom that often bothers midlife females,
      migraine is closely associated with perimenopause. Previous studies suggest that
      one of the most prominent triggers is the sudden decline of estrogen during
      perimenopausal period. Hormone replacement therapy (HRT) is widely used to
      prevent this suffering in perimenopausal women, but effective diagnostic system
      is lacked for quantifying the severity of the diseaase. To avoid the abuse and
      overuse of HRT, we propose to conduct a diagnostic trial using multimodal MRI
      techniques to quantify the severity of these perimenopausal migraineurs who are
      susceptible to the decline of estrogen. METHODS: Perimenopausal women suffering
      from migraine will be recruited from the pain clinic of our hospital.
      Perimenopausal women not suffering from any kind of headache will be recruited
      from the local community. Clinical assessment and multi-modal MR imaging
      examination will be conducted. A follow up will be conducted once half year
      within 3 years. Pain behavior, neuropsychology scores, fMRI analysis combined
      with suitable statistical software will be used to reveal the potential
      association between these above traits and the susceptibility of migraine.
      DISCUSSION: Multi-modal imaging features of both healthy controls and
      perimenopausal women who are susceptible to estrogen decline will be acquired.
      Imaging features will include volumetric characteristics, white matter integrity,
      functional characteristics, topological properties, and perfusion properties.
      Clinical information, such as basic information, blood estrogen level,
      information of migraine, and a bunch of neurological scale will also be used for
      statistic assessment. This clinical trial would help to build an effective screen
      system for quantifying the severity of illness of those susceptible women during
      the perimenopausal period. TRIAL REGISTRATION: This study has already been
      registered at Clinical Trials. gov (ID: NCT02820974 ). Registration date:
      September 28th, 2014.

PMID- 30189860
TI  - Corticosteroids pulse therapy and oral corticosteroids therapy for IgA
      nephropathy patients with advanced chronic kidney disease: results of a
      multicenter, large-scale, long-term observational cohort study.
AB  - BACKGROUND: Corticosteroids are widely used to reduce the urine protein levels of
      patients with immunoglobulin A nephropathy (IgAN). However, their potential
      preventive effects on end-stage kidney disease (ESKD) are unclear. METHODS: We
      previously performed a large-scale, long-term multicenter cohort study of
      patients with biopsy-proven IgAN treated between 1981 and 2013 (n = 1923). Based
      on the results, we reported that corticosteroids pulse therapy was potentially
      effective for the treatment of patients with an eGFR >=30 ml/min/1.73m2 and a
      urine protein amount of >=1 g/gCr. In the present study, we extracted 766
      patients with chronic kidney disease (CKD), stage G3-G4 (15 <= estimated
      glomerular filtration rate [eGFR] < 60 mL/min/1.73m2) from the same cohort. We
      divided these patients into a steroid pulse (SP) group, oral steroid (OS) group,
      and no steroid (NS) group, and analyzed the risk of end-stage kidney disease
      (ESKD) stratified by eGFR and urine protein (UP) amounts. RESULTS: Over the
      median long-term follow-up of 70 +/- 115 months, 37.1% of the patients with UP
      >=1.0 g/day and 11.2% of the patients with UP < 1.0 g/day reached ESKD. Among the
      patients with UP >=1 g/gCr, the SP group showed significantly better renal
      outcome (p < 0.001) than the OS and NS groups. In patients with UP < 1 g/gCr,
      there were no differences in renal survival among the treatment groups. These
      trends appeared even in the CKD stage G4 patients, and were also apparent in
      patients taking renin-angiotensin system inhibitors. The unprecedented long-term
      observation period in this study may have been necessary to reveal the favorable
      effect of corticosteroids on ESKD progression. CONCLUSIONS: In our long-term
      multicenter study, Corticosteroids pulse therapy was associated with better renal
      outcomes in IgAN patients with higher UP values, even if their eGFR values were
      low.

PMID- 30189862
TI  - Response of growth and development of the Pacific oyster (Crassostrea gigas) to
      thermal discharge from a nuclear power plant.
AB  - BACKGROUND: During electricity generation of nuclear power plant, heat energy
      cannot be completely converted into electrical energy, and a part of it is lost
      in the form of thermal discharge into the environment. The thermal discharge is
      harmful to flora and fauna leading to environmental deterioration, biological
      diversity decline, and even biological extinction. RESULTS: The present study
      investigated the influence of thermal discharge from a nuclear power plant on the
      growth and development of Pacific oyster Crassostrea gigas which is widely used
      as bio indicator to monitor environmental changes. The growth of soft part and
      the gonad development of oysters were inhibited due to thermal discharge. During
      winter season, temperature elevation caused by thermal discharge promoted the
      growth of oyster shells. During summer season, the growth rate of oysters in
      thermal discharge area was significantly lower than that of the natural sea area.
      CONCLUSIONS: The results of this study provided a better understanding of
      assessing the impact of thermal discharge on the marine ecological environment
      and mariculture industry. It also provided a scientific basis for defining a safe
      zone for aquaculture in the vicinity of nuclear power plants.

PMID- 30189864
TI  - The patient journey to diagnosis and treatment of autoinflammatory diseases.
AB  - BACKGROUND: Limited data are available on the experiences of patients with
      autoinflammatory diseases (AIDs) and their families along the path to diagnosis
      and treatment. We sought to describe these experiences in patients with AIDs
      including tumor necrosis factor receptor-associated periodic syndrome (TRAPS),
      mevalonate kinase deficiency/hyperimmunoglobulin D syndrome (MKD/HIDS), and
      familial Mediterranean fever (FMF). METHODS: Ninety-minute, semi-structured
      qualitative interviews and 5-day written/video diaries were used to gather
      information on the experiences of patients with AIDs and their families. RESULTS:
      Twelve families of patients from the US (TRAPS [n = 4], MKD/HIDS [n = 5], FMF [n
      = 5]) participated in this study from August to November 2015. The study included
      two families with multiple afflicted siblings. Patients' ages ranged from 1 to 28
      years. Most parents reported realizing that something was seriously wrong with
      their child after medical emergencies and/or hospitalizations, which initiated
      the difficult path to diagnosis. For most, the process included multiple
      specialist visits, extensive and repeated testing, and many misdiagnoses. Over
      time, 92% of parents reported losing confidence in the healthcare system's
      ability to find an answer to their child's symptoms, while they also struggled
      with unsupportive school personnel and dismissive friends and relatives. Patients
      and their parents reported holding on to memories of "what life was like" before
      the onset of symptoms and mourning their subsequent loss of "normalcy." Even
      after diagnosis, patients and parents continued to feel uncertain about what to
      expect in the future. CONCLUSIONS: All families emphasized the need for efficient
      early diagnosis of AIDs. Initiatives that improve the speed and accuracy of
      diagnosis, provide more comprehensive patient education, and support patients and
      families through the illness have the potential to significantly improve the
      quality of life of patients with AIDs and their families. Healthcare providers
      should be aware of the impact of the long diagnostic journey on families and work
      to create an environment of trust and collaboration in the face of a difficult
      and prolonged diagnostic process.

PMID- 30189863
TI  - Q&A: Array tomography.
AB  - Array tomography encompasses light and electron microscopy modalities that offer
      unparalleled opportunities to explore three-dimensional cellular architectures in
      extremely fine structural and molecular detail. Fluorescence array tomography
      achieves much higher resolution and molecular multiplexing than most other
      fluorescence microscopy methods, while electron array tomography can capture
      three-dimensional ultrastructure much more easily and rapidly than traditional
      serial-section electron microscopy methods. A correlative fluorescence/electron
      microscopy mode of array tomography furthermore offers a unique capacity to merge
      the molecular discrimination strengths of multichannel fluorescence microscopy
      with the ultrastructural imaging strengths of electron microscopy. This essay
      samples the first decade of array tomography, highlighting applications in
      neuroscience.

PMID- 30189865
TI  - Iatrogenic cerebral arterial gas embolism from flushing of the arterial line in
      two calves.
AB  - BACKGROUND: Measurement of invasive blood pressure as reflection of blood flow
      and tissue perfusion is often carried out in animals during general anesthesia.
      Intravascular cannulation offers the potential for gas to directly enter the
      circulation and lead to arterial gas embolism. Cerebral arterial gas embolism may
      cause a spectrum of adverse effects ranging from very mild symptoms to severe
      neurological injury and death. Although several experimental models of arterial
      gas embolism have been published, there are no known published reports of
      accidental iatrogenic cerebral arterial gas embolism from flushing of an arterial
      line in animals. CASE PRESENTATION: A 7-day-old Red Holstein-Friesian calf (No.
      1) and a 28-day-old Holstein-Friesian calf (No. 2) underwent hot iron disbudding
      and sham disbudding, respectively, under sedation and cornual nerve anesthesia.
      Invasive arterial blood pressure was measured throughout the procedure and at
      regular intervals during the day. Before disbudding, a sudden and severe increase
      of blood pressure was observed following flushing of the arterial line.
      Excitation, hyperextension of the limbs and rapid severe horizontal nystagmus
      appeared shortly thereafter. Over the following minutes, symptoms ameliorated and
      blood pressure normalized in both cases. Prompt diagnosis was missed in calf 1;
      supportive fluid therapy was provided. Severe deterioration of neurologic status
      occurred in the following 24 h and culminated with stupor. The calf was
      euthanized for ethical reasons and the histological examination revealed
      extensive cerebral injury. Treatment of calf 2 consisted of supportive fluid and
      oxygen therapy; furosemide (1 mg/kg IV) was injected twice. Calf 2 appeared
      clinically normal after 2 h and showed no neurologic sequelae on a 3-month-follow
      up period. CONCLUSIONS: There are no known reports of cerebral arterial gas
      embolism following flushing of the auricular arterial line in calves. The
      injection of a small amount of air at high pressure in a peripheral artery may
      lead to a significant cerebral insult. The clinical presentation is non-specific
      and can favour misdiagnosis and delay of therapy.

PMID- 30189866
TI  - Do healthcare services behave as complex systems? Analysis of patterns of
      attendance and implications for service delivery.
AB  - BACKGROUND: The science of complex systems has been proposed as a way of
      understanding health services and the demand for them, but there is little
      quantitative evidence to support this. We analysed patterns of healthcare use in
      different urgent care settings to see if they showed two characteristic
      statistical features of complex systems: heavy-tailed distributions (including
      the inverse power law) and generative burst patterns. METHODS: We conducted three
      linked studies. In study 1 we analysed the distribution of number of contacts per
      patient with an urgent care service in two settings: emergency department (ED)
      and primary care out-of-hours (PCOOH) services. We hypothesised that these
      distributions should be heavy-tailed (inverse power law or log-normal) in keeping
      with typical complex systems. In study 2 we analysed the distribution of bursts
      of contact with urgent care services by individuals: correlated bursts of
      activity occur in complex systems and represent a mechanism by which overall
      heavy-tailed distributions arise. In study 3 we replicated the approach of study
      1 using data systematically identified from published sources. RESULTS: Study 1
      involved data from a PCOOH service in Scotland (725,000) adults, 1.1 million
      contacts) and an ED in New Zealand (60,000 adults, 98,000 contacts). The total
      number of contacts per individual in each dataset was statistically
      indistinguishable from an inverse power law (p > 0.05) above 4 contacts for the
      PCOOH data and 3 contacts for the ED data. Study 2 found the distribution of
      contact bursts closely followed a heavy-tailed distribution (p < 0.008),
      indicating the presence of correlated bursts. Study 3 identified data from 17
      studies across 8 countries and found distributions similar to study 1 in all of
      them. CONCLUSIONS: Urgent healthcare use displays characteristic statistical
      features of large complex systems. These studies provide strong quantitative
      evidence that healthcare services behave as complex systems and have important
      implications for urgent care. Interventions to manage demand must address drivers
      for consultation across the whole system: focusing on only the highest users (in
      the tail of the distribution) will have limited impact on efficiency. Bursts of
      attendance - and ways to shorten them - represent promising targets for managing
      demand.

PMID- 30189867
TI  - Test-retest reliability and measurement error of the Danish WHO-5 Well-being
      Index in outpatients with epilepsy.
AB  - BACKGROUND: The generic questionnaire WHO-5 Well-being Index (WHO-5), which
      measures the construct of mental well-being has been widely used in several
      populations across countries. The questionnaire has demonstrated sufficient
      psychometric properties; however, the test- retest reliability of the WHO-5 scale
      has yet to be determined. The aim of this study was to evaluate the test-retest
      reliability and measurement error of the Danish WHO-5 Well-being Index for
      outpatients with epilepsy. A further aim was to evaluate whether the method of
      administration (web, paper, or a mixture of the two modalities) influenced the
      results. METHODS: Epilepsy outpatients aged >=15 years from three outpatient
      clinics in Central Denmark Region were included from August 2016 to April 2017.
      The participants were randomly divided into four test-retest groups: web-web,
      paper-paper, web-paper, and paper-web. Test-retest reliability was assessed by
      intraclass correlation coefficients (ICC) and measurement error by calculating
      minimal detectable change (MDC) on the basis of the standard error of the
      measurement. RESULTS: A total of 554 patients completed the questionnaire at two
      time points. The median duration between test-retest was 22 days. The pooled test
      retest reliability estimate was ICC 0.81 (95% CI 0.78; 0.84). The estimated MDC
      was 23.60 points (95% CI 22.27; 25.10). These estimates showed little variation
      across administration methods. CONCLUSIONS: WHO-5 showed acceptable test-retest
      reliability in a Danish epilepsy outpatient population across different method of
      administration; however, the relatively large measurement error should be taken
      into account when evaluating changes in WHO-5 scores over time. Further research
      should be done to explore these findings.

PMID- 30189868
TI  - Surgeons' and methodologists' perceptions of utilising an expertise-based
      randomised controlled trial design: a qualitative study.
AB  - BACKGROUND: Randomised controlled trials (RCTs) are widely recognised to be the
      most rigorous way to test new and emerging clinical interventions. When the
      interventions under study are two different surgical procedures, however,
      surgeons are required to be trained and sufficiently proficient in the different
      surgical approaches to take part in such a trial. It is often the case that even
      where surgeons can perform both trial surgical procedures, they have a preference
      and/or have more expertise in one of the procedures. The expertise-based trial
      design, where participating surgeons only provide the procedure in which they
      have appropriate expertise, has been proposed to overcome this problem. When
      expertise-based designs should be best used remains unclear; such approaches may
      be more suited to addressing specific questions. The aim of this qualitative
      study was to improve understanding about the range of views that surgeons and
      methodologists have regarding the use of the expertise-based RCT design. METHODS:
      Twelve individual interviews with surgeons and methodologists with experience of
      surgical trials were conducted. Interviews were semi-structured and conducted
      face-to-face or by telephone. Interviews were audio-recorded, transcribed and
      analysed systematically using an interpretive approach. RESULTS: Both surgeons
      and methodologists saw potential advantages in the expertise-based design
      particularly in terms of surgeons' participation and in trials where the
      procedures being evaluated were significantly different. The main disadvantages
      identified were methodological (e.g. the potential for surgeons carrying out one
      of the trial procedure being systematically different) and operational (e.g. the
      need to 'transfer' patients between surgeons with potential consequences for the
      surgeon/patient relationship). CONCLUSION: This study suggests that the expertise
      based trial design has significant potential to increase surgeon participation in
      trials in some settings. In other settings the standard design was generally seen
      as the preferable design. Particularly suitable conditions for an expertise-based
      design include those where the surgical procedures under evaluation are
      substantially different, where they are routinely delivered by different health
      professionals/surgeons with clear proficiencies in each; and contexts in which a
      multiple-surgeon model is in use and trust between the patient and surgeons can
      be suitably protected. The standard design was seen by most participants as the
      default design. Several logistical and methodological concerns remain to be
      addressed before the expertise-based design is likely to be more widely adopted.

PMID- 30189869
TI  - A novel scoring system to guide prognosis in patients with pathological
      fractures.
AB  - BACKGROUND: The most appropriate treatment of pathological fractures from
      metastatic disease depends on several factors, one of the most important being
      predicted life expectancy. The aim of this study was to identify the variables
      that influence prognosis and utilise these to develop a novel scoring system to
      better predict life expectancy post-pathological fracture. METHODS: The records
      of all patients that presented with metastatic pathological fractures over a 10
      year period from the only tertiary orthopaedic departments in Western Australia
      were retrospectively examined. Variables assessed were primary cancer type,
      fracture site, fixation method, cement augmentation, pre-morbid level of physical
      functioning, complication rate, treatment with chemotherapy or radiotherapy and
      appendicular, spinal and visceral metastatic load. RESULTS: A total of 233
      patients were included. Median survival from fracture to death was 4.1 months.
      Median time from cancer diagnosis to pathological fracture was 14.2 months. There
      was a statistically significant association between patient survival and primary
      cancer type, physical functional score, spinal metastatic burden and use of
      chemotherapy or radiotherapy. CONCLUSION: A novel scoring system has been
      developed that offers a survival probability based on patient's individual
      circumstances. This can guide specialist management and offer patients a more
      accurate expectation of functional outcome and survival time.

PMID- 30189870
TI  - Predictors of mental health help-seeking among polish people living the United
      Kingdom.
AB  - BACKGROUND: Migration has been shown to be associated with negative mental health
      outcomes. Moreover, migrants tend to underutilise mental health services. The
      current study aimed to assess the association between predictors, divided into
      three groups (predisposing, enabling and need), and two outcome variables: (1)
      past professional mental health help-seeking during the stay in the United
      Kingdom; (2) intentions of mental health help-seeking from a mental health
      professional within the next three months. METHODS: The study utilised a
      population-based cross-sectional survey with the final sample of 536
      participants. Multivariate linear and logistic regression models were used to
      examine the association between predictors and the outcomes. RESULTS: We found
      strong evidence that older age, mental health stigma and living circumstances
      (predisposing factors), as well as knowledge of the National Health Service,
      social support, and education (enabling factors) were associated with past and
      future help-seeking for mental health problems. Finally, mental health status was
      associated with both past help-seeking and intentions. CONCLUSION: Due to large
      numbers of migrants in the UK it is vital to ensure that these populations
      receive adequate mental health support. Findings of the present study may inform
      development of policies and interventions better tailored to specific migrant
      populations.

PMID- 30189871
TI  - FOXC1 induces cancer stem cell-like properties through upregulation of beta
      catenin in NSCLC.
AB  - BACKGROUND: Accumulating evidence suggests that cancer stem cells (CSCs) play a
      critical role in tumor initiation, progression and therapy, and recent studies
      have indicated that Forkhead box C1 (FOXC1) is strongly associated with CSCs.
      This study investigates the regulatory effects of FOXC1 on CSC-like properties in
      non-small cell lung cancer (NSCLC). METHODS: We analyzed FOXC1 expression in
      NSCLC using the Cancer Genome Atlas (TCGA) database on UALCANC and performed
      survival analyses of NSCLC patients on Human Protein Atlas. CSC-like properties
      were analyzed based on CSC marker-positive cell population, self-renewal ability,
      stemness-related gene expression, tumorigenicity and drug resistance. The
      percentage of CD133+ cells was analyzed by flow cytometric analysis. Self-renewal
      ability was detected by sphere-formation analysis. Real-time PCR, western
      blotting and immunohistochemical staining were employed to detect mRNA and
      protein levels. Tumorigenicity was determined based on a xenograft formation
      assay, and effects of FOXC1 on drug resistance were assessed by cell viability
      and apoptosis assays. Luciferase reporter and chromatin immunoprecipitation
      (ChIP) assays were used to investigate the binding of FOXC1 to beta-catenin
      promoter. RESULTS: FOXC1 expression was found to be elevated in NSCLC tissues and
      negatively correlated with patient survival. FOXC1 knockdown reduced CD133+ cell
      percentage, suppressed self-renewal ability, decreased expression of stemness
      related genes (Oct4, NANOG, SOX2 and ABCG2) and inhibited NSCLC cell
      tumorigenicity in vivo. Moreover, FOXC1 knockdown increased cisplatin and
      docetaxel sensitivity and reduced gefitinib resistance, whereas FOXC1
      overexpression enhanced CSC-like properties. Luciferase reporter and ChIP assays
      showed beta-catenin to be a direct transcriptional target of FOXC1. Furthermore,
      overexpression of beta-catenin reversed the CSC-like property inhibition induced
      by FOXC1 knockdown, and knockdown of beta-catenin attenuated the CSC-like
      properties induced by FOXC1 overexpression. CONCLUSIONS: This study demonstrates
      that FOXC1 induces CSC-like properties in NSCLC by promoting beta-catenin
      expression. The findings indicate that FOXC1 is a potential molecular target for
      anti-CSC-based therapies in NSCLC.

PMID- 30189873
TI  - Efficacy of Sida pilosa Retz aqueous extract against Schistosoma mansoni -
      induced granulomatous inflammation in the liver and the intestine of mice:
      histomorphometry and gastrointestinal motility evaluation.
AB  - BACKGROUND: The macerate of Sida pilosa aerial parts is used empirically for the
      treatment of intestinal helminthiasis. Previous studies have shown that Sida
      pilosa aqueous extract (SpAE) has schistosomicidal, antioxidant, anti
      inflammatory and anti-fibrotic activities in Schistosoma mansoni infection. This
      study was designed to evaluate the effect of SpAE on the granulomatous
      inflammation induced by S. mansoni in the liver and the intestine of mice by
      histomorphometry; as well as on the gastrointestinal motility. METHODS: To study
      the effect of SpAE on the liver and intestine histomorphometry and on the
      gastrointestinal motility, SpAE was administered at 200 mg/kg per os to S.
      mansoni-infected mice for 4 weeks. Praziquantel was used as reference drug. Prior
      to carrying out sacrifice, a batch of mice was subjected to gastrointestinal
      transit evaluation with 3% charcoal meal. After sacrifying another batch of mice,
      we performed histological and morphometric analyses of the liver and the ileum.
      We measured the following: total proteins, transaminases, malondialdehyde,
      nitrites, superoxide dismutase, catalase and reduced glutathione. The effect of
      SpAE (4, 8, 16 and 32 mg/mL) on the ileum contractile activity was evaluated
      either in the absence or in the presence of pharmacological blockers. RESULTS:
      SpAE induced a significant reduction of hepatosplenomegaly and intestine
      enlargement. The number of granulomas was reduced by 52.82% in the liver and
      52.79% in the intestine, whereas the volume of hepatic granulomas decreased by
      48.76% after SpAE treatment. SpAE also reduced (p < 0.001) the ileal muscular
      layer thickness. The levels of total proteins, transaminases, malondialdehyde,
      nitrites, superoxide dismutase, catalase and reduced glutathione were restored
      after treatment of infected mice with SpAE. A normalization of the
      gastrointestinal transit was also recorded after SpAE treatment. The effect of
      SpAE on intestinal motility was mediated via intracellular and extracellular
      calcium mobilization. CONCLUSION: Our findings provide evidence that SpAE
      improves granulomatous inflammation induced by S. mansoni both in the liver and
      in the intestine, as well as it re-establishes normal gastrointestinal transit.
      SpAE may be used for the development of alternative medicine against S. mansoni
      infection.

PMID- 30189872
TI  - Macrophages: friend or foe in idiopathic pulmonary fibrosis?
AB  - Idiopathic pulmonary fibrosis (IPF) is a prototype of lethal, chronic,
      progressive interstitial lung disease of unknown etiology. Over the past decade,
      macrophage has been recognized to play a significant role in IPF pathogenesis.
      Depending on the local microenvironments, macrophages can be polarized to either
      classically activated (M1) or alternatively activated (M2) phenotypes. In
      general, M1 macrophages are responsible for wound healing after alveolar
      epithelial injury, while M2 macrophages are designated to resolve wound healing
      processes or terminate inflammatory responses in the lung. IPF is a pathological
      consequence resulted from altered wound healing in response to persistent lung
      injury. In this review, we intend to summarize the current state of knowledge
      regarding the process of macrophage polarization and its mediators in the
      pathogenesis of pulmonary fibrosis. Our goal is to update the understanding of
      the mechanisms underlying the initiation and progression of IPF, and by which, we
      expect to provide help for developing effective therapeutic strategies in
      clinical settings.

PMID- 30189874
TI  - Development of the Organisational Health Literacy Responsiveness (Org-HLR) self
      assessment tool and process.
AB  - BACKGROUND: The World Health Organization describes health literacy as a critical
      determinant of health and driver of citizen empowerment and health equity.
      Several studies have shown that health literacy is associated with a range of
      socioeconomic factors including educational attainment, financial position and
      ethnicity. The complexity of the health system influences how well a person is
      able to engage with information and services. Health organisations can empower
      the populations they serve and address inequity by ensuring they are health
      literacy responsive. The aim of this study was to develop the Organisational
      Health Literacy Responsiveness self-assessment tool (Org-HLR Tool), and an
      assessment process to support organisations with application of the tool.
      METHODS: A co-design workshop with health and social service professionals was
      undertaken to inform the structure of the tool and assessment process.
      Participants critiqued existing self-assessment tools and discussed the likely
      utility of the data they generate. A review of widely used organisational
      performance assessment tools informed the structure and self-assessment process.
      The Organisational Health Literacy Responsiveness (Org-HLR) Framework (with seven
      domains/24 sub-domains) provided the structure for the assessment dimensions of
      the tool. The performance indicators were drawn from raw data collected during
      development of the Org-HLR Framework. RESULTS: Twenty-two professionals
      participated in the workshop. Based on the feedback provided and a review of
      existing tools, a multi-stage, group-based assessment process for implementing
      the Org-HLR Tool was developed. The assessment process was divided into three
      parts; i) reflection; ii) self-rating; and iii) priority setting, each supported
      by a corresponding tool. The self-rating tool, consistent with the Org-HLR
      Framework, was divided into: External policy and funding environment; Leadership
      and culture; Systems, processes and policies; Access to services and programs;
      Community engagement and partnerships; Communication practices and standards;
      Workforce. Each of these had 1 to 5 sub-dimensions (24 in total), and 135
      performance indicators. CONCLUSIONS: The Org-HLR Tool and assessment process were
      developed to address a gap in available tools to support organisations to assess
      their health literacy responsiveness, and prioritise and plan their quality
      improvement activities. The tool is currently in the field for further utility
      and acceptability testing.

PMID- 30189875
TI  - Human Alzheimer's disease gene expression signatures and immune profile in APP
      mouse models: a discrete transcriptomic view of Abeta plaque pathology.
AB  - BACKGROUND: Alzheimer's disease (AD) is a chronic neurodegenerative disease with
      pathological hallmarks including the formation of extracellular aggregates of
      amyloid-beta (Abeta) known as plaques and intracellular tau tangles. Coincident
      with the formation of Abeta plaques is recruitment and activation of glial cells
      to the plaque forming a plaque niche. In addition to histological data showing
      the formation of the niche, AD genetic studies have added to the growing
      appreciation of how dysfunctional glia pathways drive neuropathology, with
      emphasis on microglia pathways. Genomic approaches enable comparisons of human
      disease profiles between different mouse models informing on their utility to
      evaluate secondary changes to triggers such as Abeta deposition. METHODS: In this
      study, we utilized two animal models of AD to examine and characterize the AD
      associated pathology: the Tg2576 Swedish APP (KM670/671NL) and TgCRND8 Swedish
      plus Indiana APP (KM670/671NL + V717F) lines. We used laser capture microscopy
      (LCM) to isolate samples surrounding Thio-S positive plaques from distal non
      plaque tissue. These samples were then analyzed using RNA sequencing. RESULTS: We
      determined age-associated transcriptomic differences between two similar yet
      distinct APP transgenic mouse models, known to differ in proportional
      amyloidogenic species and plaque deposition rates. In Tg2576, human AD gene
      signatures were not observed despite profiling mice out to 15 months of age.
      TgCRND8 mice however showed progressive and robust induction of lysomal,
      neuroimmune, and ITIM/ITAM-associated gene signatures overlapping with prior
      human AD brain transcriptomic studies. Notably, RNAseq analyses highlighted the
      vast majority of transcriptional changes observed in aging TgCRND8 cortical brain
      homogenates were in fact specifically enriched within the plaque niche samples.
      Data uncovered plaque-associated enrichment of microglia-related genes such as
      ITIM/ITAM-associated genes and pathway markers of phagocytosis. CONCLUSION: This
      work may help guide improved translational value of APP mouse models of AD,
      particularly for strategies aimed at targeting neuroimmune and neurodegenerative
      pathways, by demonstrating that TgCRND8 more closely recapitulates specific human
      AD-associated transcriptional responses.

PMID- 30189876
TI  - Multi-focused psychosocial residential rehabilitation interventions improve
      quality of life among cancer survivors: a community-based controlled trial.
AB  - BACKGROUND: Even though multi-focused psychosocial residence rehabilitation
      intervention (MPRRI) programs are widely implemented by the Shanghai Cancer
      Rehabilitation Club, these programs have not been rigorously evaluated. In this
      study, we evaluated the effects of a 21-day MPRRI program, on the quality of life
      (QoL) among cancer survivors. METHODS: A total of 388 cancer patients were
      enrolled to either receive the 21-day MPRRI (n = 129) intervention or a waiting
      list comparison (WLC) intervention (n = 259). The intervention group was offered
      community-based 21-day MPRRI program, combining supportive-expressive group,
      cognitive-behavioral therapy, and Guolin Qigong. QoL was measured using the
      European Organization for Research and Treatment Quality of Life Version 3
      Questionnaire. Multivariable linear models were used to compare changes in QoL
      values between the two groups. RESULTS: After adjustment for the QoL score and
      other covariates at baseline, there was no significant difference in global
      health status (mean = 3.8, 95% CI - 1.3-9.0, P = 0.14) between the two groups
      after 6 months intervention. While compared with the WLC group, the intervention
      group showed significant improvements in the QoL score (all P < 0.05); however,
      there were no clinically relevant changes in subscales including emotional
      functioning (ES = 0.58), cognitive functioning (ES = 0.53), pain (ES = 0.52),
      physical functioning (ES = 0.36), and insomnia (ES = 0.30). CONCLUSIONS: These
      preliminary results suggest the MPRRI program is both feasible and acceptable
      intervention for cancer survivors in community settings and is effective in
      significant improving QoL above.

PMID- 30189877
TI  - Dosimetric analysis and comparison of reduced longitudinal cranial margins of
      VMAT-IMRT of rectal cancer.
AB  - BACKGROUND: The cranial border of the target volume (TV) in rectal cancer
      patients treated with neoadjuvant chemoradiation (nCRT) is mostly defined at the
      level of L5/S1. However, current studies have shown that relapse cranially of the
      target volume after neoadjuvant nCRT and surgery is very rare. A reduction of
      cranial TV margins could be reasonable to reduce toxicity to the organs at risk
      (OAR). In this study we compared the dose distribution to the OAR for different
      cranial longitudinal margins using a dose-volume histogram (DVH) analysis.
      METHODS: Ten patients with loco regional advanced rectal cancer were analysed
      retrospectively. All patients were planned for Volumetric Arc Therapy Radiation
      Therapy (VMAT). Next to the original PTV (PTV0), three new planning target
      volumes (PTV) were defined for each patient: The PTV0 reduced by 1 cm, 2 cm and 3
      cm on cranial extension. For each PTV a treatment plan with a total dose of 50.4
      Gy with daily doses of 1.8 Gy was calculated. Dose to the OAR were evaluated and
      compared. RESULTS: For the bone marrow, the small bowel and the peritoneal space
      all clinically relevant relative dose parameters (V10-V50) as well as the Dmedian
      could be significantly reduced with every cranial target volume reduction of 1
      cm. For V10 of the peritoneal space the dose could be nearly halved with a 3 cm
      shortened TV. After TV reduction of 3 cm also for the urinary bladder a
      significant dose reduction of the Dmedian could be achieved. CONCLUSIONS:
      Considering the very low recurrence rates in the TME and IMRT era, the
      distribution patterns of these relapses as well as the relevant side effects of
      nCRT, we would agree with existing recommendations of reduction of the cranial
      target volume in nCRT treated rectal cancer patients.

PMID- 30189878
TI  - Impulsivity and consideration of future consequences as moderators of the
      association between emotional eating and body weight status.
AB  - BACKGROUND: Emotional eating (EmE) is characterized by an over consumption of
      food in response to negative emotions and is associated with an increased weight
      status. Consideration of Future Consequences (CFC) or a low level of impulsivity
      could influence the association between EmE and weight status. The objective was
      to analyze the moderating influence of CFC and impulsivity on the relationship
      between EmE and BMI. METHODS: A total of 9974 men and 39,797 women from the
      NutriNet-Sante cohort study completed the revised 21-item Three-Factor Eating
      Questionnaire to assess their EmE, the CFC questionnaire (CFC-12) to assess their
      level of time perspective, and the Barratt Impulsiveness Scale (BIS-11) to assess
      their impulsivity. Weight and height were self-reported each year over a median
      follow-up of 5.3 years. The associations between EmE and repeated measures of BMI
      were estimated by multiple linear mixed-effects regression models stratified by
      gender, tertiles of the CFC, or tertiles of the BIS-11, taking into account
      sociodemographic and lifestyle factors. RESULTS: Overall, EmE was positively
      associated with BMI. CFC and impulsivity did not moderate the effect of EmE on
      changes of BMI per year, but quantitatively moderated the effect of EmE on
      overall BMI. In women, the strength of the association between EmE and weight
      status increased with CFC level. Difference of BMI slopes between a low and a
      high level of CFC was - 0.43 kg/m2 (95% CI: -0.55, - 0.30) (p < .0001). In
      addition, the strength of the association between emotional eating and weight
      status increased with impulsivity level. Difference of BMI slopes between a low
      and a high level of impulsivity was + 0.37 kg/m2 (95% CI: 0.24, 0.51) (p <
      .0001). In men, only individuals with a low CFC presented a stronger association
      of EmE with BMI. CONCLUSIONS: Impulsivity and consideration of future
      consequences moderated the association between emotional eating and body weight
      status. This study emphasizes the importance of taking into account psychological
      traits in obesity prevention.

PMID- 30189879
TI  - DigitalMe: a journey towards personalized health and thriving.
AB  - The use of information and communication technologies for health (eHealth)
      delivered via mobile-based or digitally enhanced solutions (mHealth) have rapidly
      evolved. When used together across various mobile applications and devices
      eHealth and mHealth technologies have the ability to passively monitor behavior
      as an indicator of socialization and mood; accumulate a range of biomedical data
      such as weight and heart rate; and track metrics associated with activities
      including steps taken and hours slept. Yet, these technologies are insufficient
      for measuring the full array of data about an individual and the impact of that
      data on a person's current and future health. Digital health converges eHealth
      and mHealth with patient data about their health, healthcare, living, and
      environment with genomics. An innovative opportunity to unravel the complexities
      of disease and aging is increasingly possible with an integrative multi-omics
      approach informed by multidisciplinary sciences including medicine, design,
      biomedical informatics and engineering. The digitization of individual level data
      from all available sources makes possible the development of DigitalMeTM, a
      personalized virtual avatar of a real person. The combination of longitudinally
      collected person generated data and molecular data derived from biospecimens
      offers researchers unique opportunities to better understand the mechanisms of
      disease while advancing person-centric hypotheses generation related to
      treatments, diagnostics, and prognostics.

PMID- 30189880
TI  - Circulating tumor cells criteria (CyCAR) versus standard RECIST criteria for
      treatment response assessment in metastatic colorectal cancer patients.
AB  - BACKGROUND: The use of circulating tumor cells (CTCs) as indicators of treatment
      response in metastatic colorectal cancer (mCRC) needs to be clarified. The
      objective of this study is to compare the Response Evaluation Criteria in Solid
      Tumors (RECIST) with the Cytologic Criteria Assessing Response (CyCAR), based on
      the presence and phenotypic characterization of CTCs, as indicators of FOLFOX
      bevacizumab treatment response. METHODS: 77 mCRC blood samples from FOLFOX
      bevacizumab treated patients were analyzed to isolate CTCs before and after (12
      and 24 weeks) treatment, using an immunomagnetic separation method. VEGFR
      expression was identified by double immunostaining. RESULTS: We observed a
      decrease of CTCs (42.8 vs. 18.2%) and VEGFR positivity (69.7% vs. 41.7%) after
      treatment. According to RECIST, 6.45% of the patients did not show any clinical
      benefit, whereas 93.55% patients showed a favorable response at 12 weeks.
      According to CyCAR, 29% had a non-favorable response and 71% patients did not. No
      significant differences were found between the response assessment by RECIST and
      CyCAR at 12 or 24 weeks. However, in the multivariate analysis, RECIST at 12
      weeks and CyCAR at 24 weeks were independent prognostic factors for OS (HR: 0.1,
      95% CI 0.02-0.58 and HR: 0.35, 95% CI 0.12-0.99 respectively). CONCLUSIONS: CyCAR
      results were comparable to RECIST in evaluating the response in mCRC and can be
      used as an alternative when the limitation of RECIST requires additional response
      analysis techniques.

PMID- 30189881
TI  - A systematic review and meta-analysis of direct anterior approach versus
      posterior approach in total hip arthroplasty.
AB  - BACKGROUND: This meta-analysis aimed to evaluate the postoperative clinical
      outcomes and safety of the direct anterior approach (DAA) versus posterior
      approach (PA) in total hip arthroplasty (THA). METHODS: We searched PubMed,
      Embase, Web of Science, the Cochrane Library, and Google databases from inception
      to June 2018 to select studies that compared the DAA and PA for THA. Only
      randomized controlled trials (RCTs) were included. Outcomes included Harris hip
      score at 2 weeks, 6 weeks, 12 weeks, and 1 year; VAS at 24 h, 48 h, and 72 h;
      incision length, operation time, postoperative blood loss, length of hospital
      stay, and complications (intraoperative fracture, postoperative dislocation,
      heterotopic ossification (HO), and groin pain). RESULTS: Nine RCTs totaling 754
      THAs (DAA group = 377, PA group = 377) met the criteria to be included in this
      meta-analysis. The present meta-analysis indicated that, compared with PA group,
      DAA group was associated with an increase of the Harris hip score at the 2-week
      and 4-week time points. No significant difference was found between DAA and PA
      groups of the Harris hip scores at 12 weeks, 1 year length of hospital stay (p >
      0.05). DAA group was associated with a reduction of the VAS at 24 h, 48 h, and 72
      h with statistical significance (p < 0.05). What is more, DAA was associated with
      a reduction of the incision length and postoperative blood loss (p < 0.05). There
      was no significant difference between the operation time and complications
      (intraoperative fracture, postoperative dislocation, HO, and groin pain).
      CONCLUSION: In THA patients, compared with PA, DAA was associated with an early
      functional recovery and less pain scores. What is more, DAA was associated with
      shorter incision length and blood loss.

PMID- 30189883
TI  - Modelling the spatial distribution of aquatic insects (Order Hemiptera)
      potentially involved in the transmission of Mycobacterium ulcerans in Africa.
AB  - BACKGROUND: Biting aquatic insects belonging to the order Hemiptera have been
      suggested as potential vectors of Mycobacterium ulcerans in endemic areas for
      Buruli ulcer (BU). If this is the case, these insects would be expected to co
      exist with M. ulcerans in the same geographical areas. Here, we studied the
      geographical distribution of six aquatic Hemiptera families that are thought to
      be vectors of M. ulcerans and explored their potential geographical overlapping
      with communities reporting BU cases in endemic countries. METHODS: We have
      developed ensemble ecological models of predicted distribution for six families
      of the Hemiptera (Naucoridae, Belostomatidae, Notonectidae, Nepidae, Corixidae
      and Gerridae) applying a robust modelling framework over a collection of recorded
      presences and a suite of environmental and topographical factors. Ecological
      niche factor analysis (ENFA) was first used to identify factors that best
      described the ecological niches for each hemipteran family. Finally, we explored
      the potential geographical co-occurrence of these insects and BU in two endemic
      countries, Cameroon and Ghana. RESULTS: Species of the families Naucoridae and
      Belostomatidae, according to our models, are widely distributed across Africa,
      although absent from drier and hotter areas. The other two families of biting
      Hemiptera, the Notonectidae and Nepidae, would have a more restricted
      distribution, being more predominant in western and southern Africa. All these
      four families of biting water bugs are widely distributed across coastal areas of
      West Africa. They would thrive in areas where annual mean temperature varies
      between 15-22  degrees C, with moderate annual precipitation (i.e. 350-1000
      mm/annual) and near to water courses. Species of all hemipteran families show
      preference for human-made environments such as agricultural landscapes and
      urbanized areas. Finally, our analysis suggests that M. ulcerans and species of
      these aquatic insects might coexist in the same ecological niches, although there
      would be variation in species diversity between BU endemic areas. CONCLUSIONS:
      Our findings predict the geographical co-existence of some species of aquatic
      hemipteran families and BU. Considering the existing biological evidence that
      points to some of these aquatic insects as potential phoretic vectors of M.
      ulcerans, its presence in BU endemic areas should be considered a risk factor.
      The ecological models here presented may be helpful to inform future
      environmental based models intended to delineate the potential geographical
      distribution of BU in the African region.

PMID- 30189882
TI  - How has the cost of antiretroviral therapy changed over the years? A database
      analysis in Italy.
AB  - BACKGROUND: The number of human immunodeficiency virus (HIV)-related
      hospitalizations has decreased worldwide in recent years, due to the availability
      of combined antiretroviral therapies (cART). The present analysis aimed to
      analyse the economic, and clinical burden of HIV management, after the
      introduction of systematic use of cART. METHODS: Data from HIV-infected patients,
      treated at Policlinico San Martino Hospital in Genova (Italy) were
      retrospectively collected. A comparison between years 2009 and 2015 was
      performed. HIV-related admissions were identified by using the Diagnosis-Related
      Group (DRG) codes. The resource consumption of outpatient services was derived by
      using a modelling approach. Expenditure for drugs was also analysed, as aggregate
      data. RESULTS: The number of HIV-infected patients was 898 in 2009 and 1006 in
      2015. Overall, the virological success rate improved from 2009 to 2015, as the
      percentage of patients with HIV-RNA < 50 copies/mL increased from 79 to 89% (P <
      0.05). The average incidence of hospitalizations per-patient decreased from 0.30
      in 2009, to 0.13 in 2015. Average expenditure per-patient decreased from ?10,107
      in 2009 to ?9063 in 2015. CONCLUSIONS: The present analysis confirmed the role of
      cART in controlling HIV viral load and, consequently, in reducing
      hospitalizations, admissions to day-hospital and the use of outpatient services.
      Clinical improvements and economic savings more than compensated the investments
      required to treat HIV-infected patients with cART. Health Authorities should
      invest in modern cART supply and universal treatment, to use at best the
      available resources and obtain a cost-effective improvement of health in people
      living with HIV. Additional research, with the involvement of different centers
      and the use of patient-specific data, are recommended to consolidate the findings
      of this analysis.

PMID- 30189884
TI  - Molecular and serological survey of lyssaviruses in Croatian bat populations.
AB  - BACKGROUND: Rabies is the only known zoonotic disease of bat origin in Europe.
      The disease is caused by species belonging to the genus Lyssavirus. Five
      Lyssavirus species, i.e., European bat lyssavirus (EBLV)-1, EBLV-2, Bokeloh bat
      lyssavirus, Lleida bat lyssavirus, and West Caucasian bat virus, have been
      identified in European bats. More recently, a proposed sixth species, Kotalahti
      bat lyssavirus, was detected. Thus, in this study, active surveillance was
      initiated in order to obtain insights into the prevalence of lyssaviruses in
      Croatian bat populations and to improve our understanding of the public health
      threat of infected bats. RESULTS: In total, 455 bats were caught throughout
      Continental and Mediterranean Croatia. Antibodies were found in 20 of 350 bats
      (5.71%, 95% confidence interval 3.73-8.66). The majority of seropositive bats
      were found in Trbusnjak cave (Continental Croatia, Eastern part), and most
      seropositive bats belonged to Myotis myotis (13/20). All oropharyngeal swabs were
      negative for the presence of Lyssavirus. CONCLUSIONS: The presence of
      lyssaviruses in bat populations was confirmed for the first time in Croatia and
      Southeastern Europe. The results of this study suggest the need for further
      comprehensive analyses of lyssaviruses in bats in this part of Europe.

PMID- 30189885
TI  - Optimization of a magnetic bead-based assay (MAGPIX(r)-Luminex) for immune
      surveillance of exposure to malaria using multiple Plasmodium antigens and sera
      from different endemic settings.
AB  - BACKGROUND: Serological markers are potentially useful tools for monitoring the
      progress of malaria control programs, but a better understanding of antibody
      response dynamics is necessary. The use of a magnetic bead-based immunoassay
      (MBA) is advantageous compared to ELISA, due to its multiplexing capacity, but
      limited information is available on the standardization and validation of this
      assay. METHODS: Several parameters for multiplex testing of antibodies to
      Plasmodium antigens were analysed using a set of 4 antigens and 98 sera from
      Senegalese rural asymptomatic and urban symptomatic individuals. The 4 antigens
      included Plasmodium falciparum CSP and PfAMA1 peptides, recombinant P. falciparum
      MSP4p20 and a Plasmodium malariae CSP (PmCSP) peptide. Comparisons with ELISA
      were done using MSP4p20 and whole schizont extract (SE) antigens. RESULTS: The
      use of fewer beads (1000 beads per well instead of 2000) and 5 ug of antigen per
      106 bead were validated as lower amounts. The use of a carrier protein (BSA) was
      shown to be critical when using peptides and the effect of a 24 h delayed
      measures was evaluated (5-25% signal decrease). Analysis of Ab responses showed
      almost equally high levels and prevalence in all transmission settings. Clear
      distinctions between rural and urban malaria were noted using PmCSP and SE
      antigens. CONCLUSIONS: This study underlines the importance of further
      optimization of the MBA technique and highlights the interest of using
      multistage/multispecies antigens for surveillance of malaria in endemic settings.

PMID- 30189887
TI  - Assessment of laypersons' paediatric basic life support and foreign body airway
      obstruction management skills: a validity study.
AB  - BACKGROUND: Standardised courses for laypeople in Paediatric Basic Life Support
      (PBLS) and Foreign Body Airway Obstruction Management (FBAOM) teach essential
      skills for the initiation of resuscitation by bystanders. Performance assessments
      are necessary to ensure that skills are acquired. We aimed to examine the
      validity of developed performance assessments and to determine credible pass/fail
      standards. METHODS: Validity evidence was gathered in a standardised simulated
      setting by testing participants with three different levels of PBLS/FBAOM
      experience: untrained laypersons, trained laypersons, and lifeguards. Two blinded
      raters assessed participants' performance. The reliability of test scores was
      analysed using generalizability theory, scores were compared across the three
      groups, and pass/fail-standards were established. RESULTS: A total of 33
      participants were included. More than two raters and two cases were necessary for
      PBLS to achieve a reliability coefficient above 0.80, which is considered the
      minimally acceptable level for high-stakes certification. For FBAOM, two tests or
      three raters were needed. Assessment scores differed across the three groups for
      PBLS skills, as well as for FBAOM skills (p < 0.001). Pass levels of 74% and 55%
      of the maximum score for PBLS and FBAOM, respectively, were identified as the
      levels that best discriminated between competent and non-competent laypersons.
      CONCLUSIONS: Laypersons' PBLS and FBAOM skills can be assessed in a reliable and
      valid way in a standardised simulated setting. However, multiple raters and
      scenario tests are needed to ensure sufficient reliability, which raises
      questions regarding the feasibility of performing certification tests for
      laypersons who participate in short paediatric resuscitation courses.

PMID- 30189886
TI  - Acute effects of ambient air pollution on outpatient children with respiratory
      diseases in Shijiazhuang, China.
AB  - BACKGROUND: Associations between ambient air pollution and child health outcomes
      have been well documented in developed countries such as the United States;
      however, only a limited number of studies have been conducted in developing
      countries. This study aimed to explore the acute effects of five ambient air
      pollutants (inhalable particles [PM10], fine particles [PM2.5], sulfur dioxide
      [SO2], nitrogen dioxide [NO2] and 0zone [O3]) on children hospital outpatients
      with respiratory diseases in Shijiazhuang, China. METHODS: Three years (2013
      2015) of daily data, including cause-specific respiratory outpatient records and
      the concentrations of five air pollutants, were collected to examine the short
      term association between air pollution and children's respiratory diseases; using
      a quasi-Poisson regression generalized additive model. Stratified analyses by
      season and age were also performed. RESULTS: From 2013 to 2015, a total of
      551,678 hospital outpatient records for children with respiratory diseases were
      collected in Shijiazhuang, China. A 10 MUg/m3 increase in a two-day average
      concentration (lag01) of NO2, PM2.5, and SO2 corresponded to an increase of 0.66%
      (95% confidence interval [CI]: 0.30-1.03%), 0.13% (95% CI: 0.02-0.24%), and 0.33%
      (95% CI: 0.10-0.56%) in daily hospital outpatient visits for children with
      respiratory diseases, respectively. The effects were stronger in the transition
      season (April, May, September and October) than in other seasons (the hot season
      [June to August] and the cool season [November to March]). Furthermore, results
      indicated a generally stronger association in older (7-14 years of age) than
      younger children (< 7 years of age). CONCLUSIONS: This research found a
      significant association between ambient NO2, PM2.5, and SO2 levels and hospital
      outpatient visits in child with respiratory diseases in Shijiazhuang, China.

PMID- 30189888
TI  - Characterization of a serine protease inhibitor from Trichinella spiralis and its
      participation in larval invasion of host's intestinal epithelial cells.
AB  - BACKGROUND: Trichinella spiralis serine protease inhibitor (TsSPI) was identified
      in ES proteins of adult worms (AW), the TsSPI gene was highly expressed at
      enteral stage worms (AW and newborn larvae), distributed mainly in the cuticle
      and stichosome of this nematode. Vaccination of mice with rTsSPI exhibited a
      62.2% reduction of intestinal AW and a 57.25% reduction of muscle larvae after
      larval challenge. The aim of this study was to investigate the biological
      characteristics of TsSPI and its roles in the process of T. spiralis invasion of
      host's intestinal epithelium cells (IECs). METHODS: The rTsSPI inhibition on
      trypsin enzymatic activity was detected by SDS-PAGE and spectrophotometry. The
      binding of rTsSPI with intestinal epithelium from normal mice and the primary
      cultured mouse intestinal epithelium cells (IECs) was examined by indirect
      immunofluorescent (IIF), the cellular localization of rTsSPI binding to IECs was
      observed by confocal microscopy. The inhibition of anti-rTsSPI serum on T.
      spiralis invasion of IECs was determined by an in vitro invasion assay. Anti
      rTsSPI antibody cytotoxicity on the newborn larvae (NBL) was also determined.
      RESULTS: The rTsSPI had the inhibitory activity against porcine trypsin. The
      rTsSPI specifically bound to the intestinal epithelium from normal mice and
      primary cultured mouse IECs, and the binding sites were located in IEC membrane
      and cytoplasm. Anti-rTsSPI antibodies depressed the larval invasion of IECs with
      a dose-dependent mode. Anti-rTsSPI antibodies also participated in the
      destruction of T. spiralis NBL via an ADCC-mediated manner. CONCLUSIONS: TsSPI
      might participate in the T. spiralis larval invasion of IECs and it is likely the
      potential vaccine target against T. spiralis enteral stages.

PMID- 30189889
TI  - Using predicate and provenance information from a knowledge graph for drug
      efficacy screening.
AB  - BACKGROUND: Biomedical knowledge graphs have become important tools to
      computationally analyse the comprehensive body of biomedical knowledge. They
      represent knowledge as subject-predicate-object triples, in which the predicate
      indicates the relationship between subject and object. A triple can also contain
      provenance information, which consists of references to the sources of the triple
      (e.g. scientific publications or database entries). Knowledge graphs have been
      used to classify drug-disease pairs for drug efficacy screening, but existing
      computational methods have often ignored predicate and provenance information.
      Using this information, we aimed to develop a supervised machine learning
      classifier and determine the added value of predicate and provenance information
      for drug efficacy screening. To ensure the biological plausibility of our method
      we performed our research on the protein level, where drugs are represented by
      their drug target proteins, and diseases by their disease proteins. RESULTS:
      Using random forests with repeated 10-fold cross-validation, our method achieved
      an area under the ROC curve (AUC) of 78.1% and 74.3% for two reference sets. We
      benchmarked against a state-of-the-art knowledge-graph technique that does not
      use predicate and provenance information, obtaining AUCs of 65.6% and 64.6%,
      respectively. Classifiers that only used predicate information performed superior
      to classifiers that only used provenance information, but using both performed
      best. CONCLUSION: We conclude that both predicate and provenance information
      provide added value for drug efficacy screening.

PMID- 30189891
TI  - Initial value problems for system of differential-algebraic equations in Maple.
AB  - OBJECTIVES: In this paper, we discuss a Maple package, deaSolve, of the symbolic
      algorithm for solving an initial value problem for the system of linear
      differential-algebraic equations with constant coefficients. RESULTS: Using the
      proposed Maple package, one can compute the desired Green's function of a given
      IVP. Sample computations are presented to illustrate the Maple package.

PMID- 30189890
TI  - Arhalofenate acid inhibits monosodium urate crystal-induced inflammatory
      responses through activation of AMP-activated protein kinase (AMPK) signaling.
AB  - BACKGROUND: Arhalofenate acid, the active acid form of arhalofenate, is a non
      agonist peroxisome proliferator-activated receptor gamma (PPARgamma) ligand, with
      uricosuric activity via URAT1 inhibition. Phase II studies revealed decreased
      acute arthritis flares in arhalofenate-treated gout compared with allopurinol
      alone. Hence, we investigated the anti-inflammatory effects and mechanisms of
      arhalofenate and its active acid form for responses to monosodium urate (MSU)
      crystals. METHODS: We assessed in-vivo responses to MSU crystals in murine
      subcutaneous air pouches and in-vitro responses in murine bone marrow-derived
      macrophages (BMDMs) by enzyme-linked immunosorbent assay (ELISA), SDS
      PAGE/Western blot, immunostaining, and transmission electron microscopy analyses.
      RESULTS: Oral administration of arhalofenate (250 mg/kg) blunted total leukocyte
      ingress, neutrophil influx, and air pouch fluid interleukin (IL)-1beta, IL-6, and
      CXCL1 in response to MSU crystal injection (p < 0.05 for each). Arhalofenate acid
      (100 MUM) attenuated MSU crystal-induced IL-1beta production in BMDMs via
      inhibition of NLRP3 inflammasome activation. In addition, arhalofenate acid dose
      dependently increased activation (as assessed by phosphorylation) of AMP
      activated protein kinase (AMPK). Studying AMPKalpha1 knockout mice, we elucidated
      that AMPK mediated the anti-inflammatory effects of arhalofenate acid. Moreover,
      arhalofenate acid attenuated the capacity of MSU crystals to suppress AMPK
      activity, regulated expression of multiple downstream AMPK targets that modulate
      mitochondrial function and oxidative stress, preserved intact mitochondrial
      cristae and volume density, and promoted anti-inflammatory autophagy flux in
      BMDMs. CONCLUSIONS: Arhalofenate acid is anti-inflammatory and acts via AMPK
      activation and its downstream signaling in macrophages. These effects likely
      contribute to a reduction of gout flares.

PMID- 30189892
TI  - Frequency of seizure attack and associated factors among patients with epilepsy
      at University of Gondar Referral Hospital: a cross-sectional study, Gondar, North
      West Ethiopia, 2017.
AB  - OBJECTIVE: About three-fourth of adults with new-onset epilepsy become seizure
      free with current anti-epileptic drugs, but around one-fourth of the patients
      continue to experience seizure which increases the risk of accident, disability,
      death and treatment side effects. Therefore, this study aimed to address the gap
      in determining the magnitude of the number of seizure attacks and identify the
      factors that provoke a repeated seizure in a patient with epilepsy. RESULTS: A
      total of 166(40.68%) study participants were experienced seizure attacks with a
      minimum of one and a maximum of seventeen times attacks. Perceived exposure to
      noise (adjusted incidence risk ratio (AIRR) = 1.91, 95% confidence interval (CI)
      [1.46, 2.49]), light (AIRR = 1.48, 95% CI [1.09, 2.00]), head injury (AIRR =
      1.71, 95% CI [1.14, 2.57]) and sleep deprivations (AIRR = 1.41, 95% CI [1.02,
      1.94]) were associated with increased incidence of seizure, while adherence
      adjusted odds ratio (AOR) = 18.18, 95% CI [3.49, 94.63]), being in middle wealth
      index (AOR = 3.52, 95% CI [1.14, 11.02]) and being in rich wealth index (AOR =
      4.05, 95% CI [1.54, 10.69]) were associated with inflation of zero count.

PMID- 30189893
TI  - Pemphigus vulgaris as the first manifestation of multiple myeloma: a case report.
AB  - BACKGROUND: The association between pemphigus and malignancy has been well
      documented for decades but an association between pemphigus vulgaris and multiple
      myeloma is unusual. We report a case of pemphigus vulgaris revealing multiple
      myeloma. CASE PRESENTATION: A 55-year-old Malagasy man, with no significant past
      medical history, presented with bullous and erosive skin lesions involving his
      trunk and scalp for the last 2 months. He had no mucous membrane involvement. A
      diagnosis of pemphigus vulgaris was made on skin biopsy and direct
      immunofluorescence of perilesional skin revealing immunoglobulin G deposition in
      the intercellular spaces in the epidermis. In an enzyme-linked immunosorbent
      assay, his serum autoantibody index against desmoglein-1 and 3 was found to be
      112 RU/mL and 34 RU/mL respectively. Serum immunoelectrophoresis showed a
      monoclonal gammopathy with a markedly elevated immunoglobulin G level (2880
      mg/dL) in association with a lambda free light chain. Bone marrow aspirate showed
      6% plasma cell infiltration. Further investigations, including creatinine blood
      test and whole body radiographic examinations, showed that he had initially
      clinical stage I multiple myeloma of the immunoglobulin G-lambda type. Six months
      later, bone tomography revealed vertebral compression fractures of the thoracic
      and lumbar spine that correlated with his back pain topographically. Anti-myeloma
      treatment including melphalan and prednisone led to an immediate decline in
      monoclonal immunoglobulin G concentration. Skin and hematologic remission were
      maintained for 12 months. CONCLUSIONS: Absence of mucosal involvement, lack of
      vacuolar degeneration at the interface, and absence of apoptotic, dyskeratotic
      keratinocytes ruled out paraneoplastic pemphigus in our case. Pemphigus vulgaris
      should be considered even if possible underlying disease for which paraneoplastic
      pemphigus is recognized is present.

PMID- 30189895
TI  - Prognostic significance of cell cycle-associated proteins p16, pRB, cyclin D1 and
      p53 in resected oropharyngeal carcinoma.
AB  - BACKGROUND: Human papillomavirus (HPV)-related oropharyngeal squamous cell
      carcinoma (OPSCC) has an improved outcome and may allow for treatment de
      escalation. High-risk HPV (HR-HPV) infection is associated with deregulated
      expression of the cell cycle-associated proteins p16INK4, pRB, cyclin D1 and p53.
      The objective of this study was to assess cell cycle proteins as potential
      surrogate markers for HR-HPV DNA testing to identify OPSCC with favorable
      prognosis after resection. METHODS: Tissue microarray cores of 313 surgically
      treated OPSCC were stained for p16INK4a, pRB, cyclin D1 and p53 using
      immunohistochemistry. Protein expression was scored as high or low based on the
      proportion of positive carcinoma cells. Tumor samples were analysed for HR-HPV
      DNA with polymerase chain reaction-based testing. Associations between cell cycle
      protein expression and HR-HPV DNA status were evaluated by calculating
      sensitivity, specificity, predictive values, and diagnostic odds ratios (DOR).
      Kaplan-Meier and Cox regression analysis were applied to evaluate associations
      between cell cycle protein expression and patient outcome. RESULTS: High
      expression of p16INK4a, cyclin D1, pRB and p53 in tumor cells were observed in
      51.8%, 51.4%, 41.9% and 33.5% of OPSCC, respectively. HR-HPV DNA positive were
      158/313 (50.5%) tumor samples (HPV16: 147, HPV18: 1, HPV33: 5, HPV35: 2, HPV56:
      2, and HPV59: 1). P16INK4a showed a higher DOR to predict HR-HPV DNA positivity
      than pRB, cyclin D1 and p53. Both the p16INK4a/pRB and the p16INK4a/pRB/cyclin
      D1/p53 signatures had lower DOR than p16INK4a alone. Improved 5-year overall and
      disease-specific survival were associated with HR-HPV DNA positivity, high
      p16INK4a, low pRB, low cyclin D1, and low p53 expression. Associations with
      improved outcome were also observed for the marker combinations high
      p16INK4a/positive HR-HPV DNA, high p16INK4a/low pRB and high p16INK4a/low pRB/low
      cyclin D1/low p53. In a multivariate analysis adjusted for age, smoking history,
      pT and pN category, high p16INK4a expression showed the lowest hazard ratio for
      death. CONCLUSIONS: High p16INK4a expression is a reliable marker for survival
      prognostication in surgically treated OPSCC patients. Protein signatures
      including the pRB, cyclin D1 and p53 proteins do not further increase the
      prognostic performance of p16INK4a as a single marker.

PMID- 30189894
TI  - Protective immunity against Trichinella spiralis in mice elicited by oral
      vaccination with attenuated Salmonella-delivered TsSP1.2 DNA.
AB  - Trichinellosis is a worldwide important food-borne zoonosis caused mainly by
      ingesting raw or undercooked pork infected with Trichinella spiralis larvae. The
      development of vaccine is needed for preventing swine from Trichinella infection
      to ensure pork safety. Previous studies showed that T. spiralis serine protease
      1.2 (TsSP1.2) is a vaccine candidate against Trichinella infection. In this
      study, the complete TsSP1.2 cDNA sequences were cloned into pcDNA3.1, and the
      rTsSP1.2 DNA was transformed into attenuated Salmonella typhimurium strain
      DeltacyaSL1344. Oral vaccination of mice with Salmonella-delivered rTsSP1.2 DNA
      vaccine induced an obvious intestinal mucosal IgA response and a systemic Th1/Th2
      immune response; the vaccinated mice showed a 33.45% reduction of intestinal
      adult worms and 71.84% reduction of muscle larvae after T. spiralis larval
      challenge. The protection might be due to the rTsSP1.2-induced production of
      specific anti-TsSP1.2 sIgA, IgG, IgG1/IgG2a, and secretion of IFN-gamma, IL-4 and
      IL-10, which protected intestinal mucosa from the parasite invasion, inhibited
      worm development and reduced female fecundity. The results indicate that the
      attenuated Salmonella-delivered rTsSP1.2 DNA vaccine offers a prospective
      strategy for the prevention and control of animal Trichinella infection.

PMID- 30189897
TI  - Improvement of the quality payment program by improving data reporting process:
      an action research.
AB  - BACKGROUND: Successful implementation of pay-for-quality (P4Q) programs mostly
      depends upon a valid, timely, and reliable data about quality measures generated
      by providers, and interpreted by payers. The aim of this study was to establish a
      data reporting method for P4Q program through an action research. METHODS:
      Qualitative method was used to align theory with action through a three-cycle
      action research. The study was conducted in September 15, 2015 to March 15, 2017,
      in East-Azerbaijan, Iran. The purposeful sampling was used to select
      participants. The participants included healthcare providers, staff in district
      health centers (DHC), experts, and managers in the provincial primary health
      center (PPHC). Data was collected by interviews, focus group discussions, and
      expert panels. Content analysis was used to synthesize the data. In each step,
      decisions about data reporting methods were made through a consensus of expert
      panel members. RESULTS: The most important dimensions of data reporting method
      were data entry and accuracy, data reporting, data analysis and interpretations,
      the flexibility of method, and training. By establishment of an online data
      reporting system for the P4Q program, a major improvement was observed in the
      documentation of performance data, the satisfaction of health care providers and
      staff (e.g. either in DHCs or PPHC), improvement of the P4Q program and
      acceptance of the P4Q program by providers. Following the present study, the
      online system was expanded in Iran's public health system for data collection and
      estimating the amount of incentive payments in P4Q program. Moreover, more
      improvements were achieved by linking the system to EMRs and also, providing
      automated feedback to providers about their own performance. CONCLUSIONS: A web
      based computerized system with the capability of linking medical record and also
      its ability to provide feedback to healthcare providers was identified as an
      appropriate method of data reporting in the P4Q program from the viewpoints of
      participants in this study.

PMID- 30189896
TI  - Trypanosoma cruzi transmission in the wild and its most important reservoir hosts
      in Brazil.
AB  - Trypanosoma cruzi (Kinetoplastea: Trypanosomatidae) infects all tissues of its
      hosts, which along with humans, include hundreds of mammalian species in the
      Americas. The epidemiology of T. cruzi has been changing in that currently the
      majority of the cases and/or outbreaks of Chagas disease occur by the ingestion
      of comestibles contaminated by T. cruzi metacyclic forms. These cases/outbreaks
      occur in distinct regional scenarios, mainly in the Amazon biome and are related
      to the local interaction mode of humans with their surroundings, as well as with
      the overall local ecological peculiarities. As trypanosomiasis caused by T. cruzi
      is primarily a zoonosis, understanding the variables that influences its
      transmission in the wild as well as the role played by the extant fauna in the
      maintenance of the parasite, is critical in establishing control measures. Here,
      we present the results of our studies of T. cruzi infection of free ranging wild
      mammalian fauna in the five biomes of Brazil, a country of continental
      dimensions. From 1992 up to 2017, we examined a total of 6587 free-ranging non
      volant wild mammal specimens. Our studies found that 17% of mammals were
      seropositive and 8% of all animals displayed positive hemocultures indicative of
      high parasitemia and, consequently, of infectivity potential. We observed that
      opossums, mainly Philander spp. and Didelphis spp., the coati Nasua nasua, the
      capuchin monkey Sapajus libidinosus and the golden lion tamarin Leontopithecus
      rosalia, were mammal taxa that demonstrated higher rates of positive
      hemocultures. Additionally, Didelphis spp. demonstrated to be a competent
      bioaccumulator of TcI diversity. Chiroptera were distinguished for hosting the
      greatest diversity of species and genotypes of Trypanosoma spp. Additionally the
      observation of the higher host range of some Trypanosoma spp., shows the need to
      reassess the ecology of representatives of the taxon. Altogether, our results
      showed that each locality, may display distinct enzootiological and
      epidemiological scenarios that must be taken into account when it comes to
      establishing control and/or clarification campaigns of the local population.

PMID- 30189899
TI  - The effects of combined exercise intervention based on Internet and social media
      software for postoperative patients with breast cancer: study protocol for a
      randomized controlled trial.
AB  - BACKGROUND: Many randomized controlled trials have investigated the effects of
      exercise on the rehabilitation of patients with breast cancer. However, the
      exercise forms used in most previous studies were monotonous. Therefore, we
      designed a protocol to estimate the effects of combined exercise intervention
      using Internet and social media software on the rehabilitation of postoperative
      patients with BC. METHODS/DESIGN: This study protocol is a randomized control
      trial with an intervention time of 12 weeks. After completing baseline
      questionnaire and physical fitness tests, the participants are randomized to the
      study group or the control group. Procedure contents of exercise intervention in
      the study group include: via phone step-recording app, ask the individuals to
      complete the target number of steps within a specified period of exercise, four
      times per week; face-to-face remote video guidance of individuals on muscle
      training, three times per week; common knowledge of physical exercise BC
      rehabilitation will be pushed regularly by social media apps every day. The
      control group will receive normal treatment and rehabilitation according to daily
      specifications of the hospital. The primary outcome will be the quality of life.
      The secondary outcomes are physical fitness and social cognitive indicators.
      DISCUSSION: This study is a clinical trial to estimate the effects of combined
      exercise intervention based on the Internet and social media software for
      postoperative patients with breast cancer (BC). If expected results are achieved
      in this study, measures and methods of BC rehabilitation will be enriched. TRIAL
      REGISTRATION: Chinese Clinical Trial Register, ChiCTR-IPR-17012368 . Registered
      on 14 August 2017.

PMID- 30189898
TI  - Epigallocatechin gallate inhibits hepatitis B virus infection in human liver
      chimeric mice.
AB  - BACKGROUND: Persistent hepatitis B virus (HBV) infection causes liver cirrhosis
      and hepatocellular carcinoma and constitutes a major worldwide health problem.
      Currently, anti-HBV drugs are limited to peginterferon and nucleos(t)ide analogs,
      which are costly and have considerable side effects; the development of novel,
      effective anti-HBV agents is crucial. METHODS: Catechins are a major group of
      compounds found in green tea extract and epigallocatechin gallate (EGCG) has been
      shown to have antiviral properties, including inhibition of cellular entry by
      HBV. FRG (Fah-/-/ Rag2-/-/ IL-2Rgamma/-) mice were used in this study to generate
      chimeras carrying human primary hepatocytes, to facilitate investigation of the
      inhibitory effect of EGCG on HBV infection. RESULTS: Here, we show the inhibitory
      effect of EGCG on HBV infection and replication in HuS-E/2 cells. The inhibitory
      effect of EGCG on HBV infection in vivo was confirmed by monitoring HBV DNA and
      HBsAg in serum and immunostaining the liver tissues of the human liver chimeric
      mice. CONCLUSIONS: The effects of EGCG suggest a robust strategy for the
      treatment of HBV infection and EGCG may have therapeutic potential for the
      treatment of HBV-associated liver diseases.

PMID- 30189900
TI  - Feasibility study of mindfulness-based cognitive therapy for anxiety disorders in
      a Japanese setting.
AB  - OBJECTIVE: Mindfulness-based cognitive therapy (MBCT) could be a treatment option
      for anxiety disorders. Although its effectiveness under conditions of low
      pharmacotherapy rates has been demonstrated, its effectiveness under condition of
      high pharmacotherapy rate is still unknown. The aim of the study was to evaluate
      effectiveness of MBCT under the context of high pharmacotherapy rates. RESULTS: A
      single arm with pre-post comparison design was adopted. Those who had any
      diagnosis of anxiety disorders, between the ages of 20 and 74, were included.
      Participants attended 8 weekly 2-hour-long sessions followed by 2 monthly
      boosters. Evaluation was conducted at baseline, in the middle, at end of the
      intervention, and at follow-up. The State-Trait Anxiety Inventory (STAI)-state
      was set as the primary outcome. Pre-post analyses with mixed-effect models
      repeated measures were conducted. Fourteen patients were involved. The mean age
      was 45.0, and 71.4% were female. The mean change in the STAI-state at every point
      showed statistically significant improvement. The STAI-trait also showed
      improvement at a high significance level from the very early stages. The
      participants showed significant improvement at least one point in some other
      secondary outcomes. Trial registration Retrospectively registered at the
      University Hospital Medical Information Network on 1st August 2013 (ID:
      UMIN000011347).

PMID- 30189901
TI  - The role of RORalpha in salivary gland lesions in patients with primary Sjogren's
      syndrome.
AB  - BACKGROUND: The orphan nuclear receptors retinoic acid-related receptor alpha and
      gammat (RORalpha and RORgammat) are critical in the development of T helper 17
      (Th17) cells, and ROR-specific synthetic ligands have proven efficacy in several
      mouse models of autoimmunity. However, the pathological significance of RORalpha
      in primary Sjogren's syndrome (pSS) remains to be elucidated. The present study
      was designed to clarify the significance of RORalpha in the pathogenesis of pSS.
      METHODS: RORalpha expression in the labial salivary gland (LSG) was determined by
      immunohistochemical analysis using a quantitative scoring system in 34 patients
      with pSS. The correlation between RORalpha expression in LSGs and the focus score
      (FS) was determined, and Th17 and IL-17 receptor A (1L-17RA) levels in LSGs were
      determined. To investigate the effect of RORs and the therapeutic potential of
      targeting RORs in pSS, we administered SR1001, a selective RORalpha/gammat
      inverse agonist, to non-obese diabetic (NOD) mice. RESULTS: The expression of
      RORalpha was significantly increased in LSGs of patients with pSS and intensified
      with disease stage/FS, showing a similar increasing trend with IL-17A and IL
      17RA. SR1001 significantly improved salivary gland secretory function and
      relieved sialadenitis in treated mice. CONCLUSION: Our data reveal the importance
      of RORalpha in controlling pathologic lymphocytic infiltration of the salivary
      glands and suggest that RORalpha may be a druggable target in treating pSS.

PMID- 30189902
TI  - Number-needed-to-treat analysis of clinical progression in patients with
      metastatic castration-resistant prostate cancer in the STRIVE and TERRAIN trials.
AB  - BACKGROUND: This analysis estimated the number needed to treat with enzalutamide
      versus bicalutamide to achieve one additional patient with chemotherapy-naive
      metastatic castration-resistant prostate cancer who would obtain clinical benefit
      regarding progression-free survival, radiographic progression-free survival, or
      no prostate-specific antigen progression at 1 and 2 years following treatment
      initiation. METHODS: Clinical event rates were obtained from the STRIVE
      (NCT01664923) and TERRAIN (NCT01288911) trials, and the number needed to treat
      was the inverse of the absolute rate difference between the event rates of
      enzalutamide and bicalutamide. The 95% Confidence Interval of the number needed
      to treat was derived from the 95% Confidence Interval of the event rate
      difference. RESULTS: Using STRIVE data (patients with metastatic disease: n = 128
      enzalutamide; n = 129 bicalutamide) comparing enzalutamide with bicalutamide at 1
      and 2 years, the numbers needed to treat to achieve one additional patient with
      chemotherapy-naive metastatic castration-resistant prostate cancer with
      progression-free survival were 2.0 and 2.8, respectively; with radiographic
      progression-free survival, 2.6 and 3.0, respectively; and without prostate
      specific antigen progression, 1.8 and 2.4, respectively. Using TERRAIN data (n =
      184 enzalutamide; n = 191 bicalutamide) comparing enzalutamide with bicalutamide
      at 1 and 2 years, the numbers needed to treat to achieve one additional patient
      with progression-free survival were 4.3 and 3.7, respectively; with radiographic
      progression-free survival, 10.0 and 2.8, respectively; and without prostate
      specific antigen progression, 2.1 and 3.2, respectively. CONCLUSIONS: The
      combined data from TERRAIN and STRIVE demonstrated that treating chemotherapy
      naive metastatic castration-resistant prostate cancer with enzalutamide leads to
      more patients without clinical progression at 1 and 2 years than with
      bicalutamide. TRIAL REGISTRATION: STRIVE (NCT01664923; registration date: August
      10, 2012) and TERRAIN (NCT01288911; registration date: February 1, 2011).

PMID- 30189904
TI  - Subjective social status and neural processing of race in Mexican American
      adolescents.
AB  - Adolescence is a sensitive period for sociocultural development in which facets
      of social identity, including social status and race, become especially salient.
      Despite the heightened importance of both social status and race during this
      developmental period, no known work has examined how individual differences in
      social status influence perceptions of race in adolescents. Thus, in the present
      study, we investigated how both subjective social status and objective
      socioeconomic status (SES) influence neural responses to race. Twenty-three
      Mexican American adolescents (15 females; mean age = 17.22 years) were scanned
      using functional magnetic resonance imaging while they viewed Black and White
      faces in a standard labeling task. Adolescents rated their subjective social
      status in US society, while their parents responded to questions about their
      educational background, occupation, and economic strain (objective SES). Results
      demonstrated a negative association between subjective social status and neural
      responses in the amygdala, fusiform face area, and medial prefrontal cortex when
      adolescents viewed Black (relative to White) faces. In other words, adolescents
      with lower subjective social status showed greater activity in neural regions
      involved in processing salience, perceptual expertise, and thinking about the
      minds of others when they viewed images of Black faces, suggesting enhanced
      salience of race for these youth. There was no relationship between objective SES
      and neural responses to the faces. Moreover, instructing participants to focus on
      the gender or emotion expression on the face attenuated the relationship between
      subjective social status and neural processing of race. Together, these results
      demonstrate that subjective social status shapes the way the brain responds to
      race, which may have implications for psychopathology.

PMID- 30189903
TI  - Expression of free radicals by peritoneal cells of sheep during the early stages
      of Fasciola hepatica infection.
AB  - BACKGROUND: The majority of vaccination studies against infection with F.
      hepatica in a natural host have been conducted at the late stage of the infection
      when the host's immune response is already immunomodulated by the parasite
      towards a Th2 non-protective response. This study was aimed at analysing the
      dynamic of the cell populations present in peritoneal liquid and the production
      of free radicals by the peritoneal leukocytes in infected and vaccinated sheep
      with recombinant cathepsin L1 of F. hepatica (rFhCL1) in early stages of the
      infection. METHODS: Forty-five sheep were divided into three groups: Group 1
      remained as negative control (n = 5), Group 2 (n = 20) was challenged with F.
      hepatica and Group 3 (n = 20) was vaccinated with rFhCL1 and challenged with F.
      hepatica. After the slaughtering, peritoneal lavages were carried out at 1, 3, 9
      and 18 days post-infection (dpi) to isolate peritoneal cell populations. Flow
      cytometry was conducted to assess levels of hydrogen peroxide (H2O2) and nitric
      oxide (NO). RESULTS: There was a significant increase in the total number of
      leukocytes at 9 and 18 dpi in infected and vaccinated groups. Production of H2O2
      was significantly increased in peritoneal granulocytes in both infected and
      vaccinated groups. Production of nitric oxide showed a significant rise in the
      granulocytes and monocytes/macrophages in infected and vaccinated sheep. The NO
      production by granulocytes at 3 and 9 dpi was significantly higher in the
      vaccinated than in the infected animals. CONCLUSIONS: Experimental infection
      induced an increase in the total number of leukocytes within the abdominal cavity
      at 9 and 18 dpi, being more noticeable in vaccinated animals. Production of H2O2
      occurred mainly in granulocytes of vaccinated and infected animals. Production of
      NO was incremented in vaccinated and non-vaccinated animals in all peritoneal
      cells. Vaccinated animals produced significant higher level of H2O2 and NO than
      infected animals.

PMID- 30189905
TI  - Serum ferritin levels are associated with insulin resistance in Chinese men and
      post-menopausal women: the Shanghai Changfeng study.
AB  - Associations between ferritin and insulin sensitivity have been described in
      recent studies. The possible association showed conflicting results by sex and
      menopausal status. We aimed to investigate the cross-sectional association of
      ferritin levels with insulin resistance and beta-cell function. A total of 2518
      participants (1033 men, 235 pre-menopausal women and 1250 post-menopausal women)
      were enrolled from the Changfeng Study. A standard interview was conducted, as
      well as anthropometric measurements and laboratory analyses, for each
      participant. The serum ferritin level was measured using electrochemiluminescence
      immunoassay. Insulin resistance and beta-cell function indices were derived from
      a homeostasis model assessment. The results showed that the serum ferritin levels
      were 250.4 (sd 165.2), 94.6 (sd 82.0) and 179.8 (sd 126.6) ng/ml in the men, pre
      menopausal and post-menopausal women, respectively. In fully adjusted models
      (adjusting for age, current smoking, BMI, waist:hip ratio, systolic blood
      pressure, diastolic blood pressure, TAG, HDL-cholesterol, LDL-cholesterol, log
      urine albumin:creatinine ratio, leucocytes, alanine aminotransferase, aspartate
      aminotransferase and gamma-glutamyl transpeptidase), serum ferritin
      concentrations are significantly associated with insulin resistance in men and
      post-menopausal females, and the null association was observed in pre-menopausal
      females. Interestingly, an increased beta-cell function associated with higher
      ferritin was observed in post-menopausal participants, but not in male
      participants. In conclusion, these results suggested that elevated serum ferritin
      levels were associated with surrogate measures of insulin resistance among the
      middle-aged and elderly male and post-menopausal women, but not in pre-menopausal
      women.

PMID- 30189906
TI  - Snow Storms and Vulnerable Populations: Local Public Health Activities in
      Response to the 2014-2015 Severe Winter Weather.
AB  - ABSTRACTThe Northeastern United States experienced some of its coldest and
      snowiest conditions ever recorded during the winter of 2014-2015. The snowfall
      and extreme temperatures created significant challenges for local health
      departments attempting to continue critical services and respond to storm-related
      needs of the community. This report from the field aims to describe the impact of
      the severe weather on local health departments' operations, to examine the
      disruption to public health services, and to document public health support
      provided to vulnerable populations during the 2014-2015 winter season. Our
      findings show that the severe weather exposed major challenges in continuity of
      public health operations across health departments of various sizes and
      highlighted some key issues as well as effective strategies, such as
      collaborations with community-based organizations, to identify and address the
      needs of the most vulnerable during the winter storms. (Disaster Med Public
      Health Preparedness. 2018;page 1 of 3).

PMID- 30189907
TI  - Liaison psychiatry services in Wales.
AB  - : Aims and methodRecent funding from Welsh Government for mental health has
      helped to develop liaison psychiatry services in Wales. Systematic data
      collection was undertaken to map the liaison psychiatry services in Wales in
      collaboration with the Royal College of Psychiatrists in Wales and Public Health
      Wales 1000 Lives Improvement. A questionnaire was designed and circulated to all
      the health boards in Wales to gather information to map liaison psychiatry
      services in Wales. Up-to-date information was confirmed in January 2018, via
      email. RESULTS: Over the past 2 years, liaison psychiatry services have been set
      up in six out of seven health boards in Wales. Staffing levels have increased and
      the remit of services has broadened.Clinical implicationsMapping has highlighted
      that liaison psychiatry services in Wales continue to evolve. It will be
      important to continue to monitor these developments and their effects. Comparison
      with services in England will provide a useful comparison of service provision. A
      particular challenge will be to establish and monitor liaison psychiatry
      standards in Wales.Declaration of interestNone.

PMID- 30189908
TI  - Psychological Resilience as a Predictor of Persistent Post-Concussive Symptoms in
      Children With Single and Multiple Concussion.
AB  - OBJECTIVES: To evaluate the relationship of psychological resilience to
      persistent post-concussive symptoms (PCS) in children with a history of single or
      multiple concussions, as well as orthopedic injury (OI). METHODS: Participants
      (N=75) were children, ages 8-18 years, who sustained a single concussion (n=24),
      multiple concussions (n=25), or an OI (n=26), recruited from a tertiary care
      children's hospital. All participants sustained injuries at least 6 months before
      recruitment, with an average time since injury of 32.9 months. Self-reported
      psychological resilience was measured using the Connor-Davidson Resilience Scale,
      and both self- and parent-reported PCS were measured using the Post-Concussion
      Symptom Inventory. Hierarchical regression analyses examined psychological
      resilience as a predictor of PCS, both as a main effect and as a moderator of
      group differences. RESULTS: Multiple concussions and low psychological resilience
      were both significant predictors of persistent PCS. Resilience was not a
      significant moderator of group differences in PCS. CONCLUSIONS: Sustaining
      multiple concussions may increase a child's risk of persistent PCS; however, high
      psychological resilience may serve as a protective factor, regardless of the
      number or type of injuries sustained. These findings provide support for
      developing and testing interventions aimed at increasing psychological resilience
      as a potential means of improving outcomes for children suffering from persistent
      PCS after concussion. (JINS, 2018, 24, 759-768).

PMID- 30189909
TI  - Addenbrooke's Cognitive Examination III: Psychometric Characteristics and
      Relations to Functional Ability in Dementia.
AB  - OBJECTIVES: The Addenbrooke's Cognitive Examination (ACE) is a common cognitive
      screening test for dementia. Here, we examined the relationship between the most
      recent version (ACE-III) and its predecessor (ACE-R), determined ACE-III cutoff
      scores for the detection of dementia, and explored its relationship with
      functional ability. METHODS: Study 1 included 199 dementia patients and 52
      healthy controls who completed the ACE-III and ACE-R. ACE-III total and domain
      scores were regressed on their corresponding ACE-R values to obtain conversion
      formulae. Study 2 included 331 mixed dementia patients and 87 controls to
      establish the optimal ACE-III cutoff scores for the detection of dementia using
      receiver operator curve analysis. Study 3 included 194 dementia patients and
      their carers to investigate the relationship between ACE-III total score and
      functional ability. RESULTS: Study 1: ACE-III and ACE-R scores differed by <=1
      point overall, the magnitude varying according to dementia type. Study 2: a new
      lower bound cutoff ACE-III score of 84/100 to detect dementia was identified
      (compared with 82 for the ACE-R). The upper bound cutoff score of 88/100 was
      retained. Study 3: ACE-III scores were significantly related to functional
      ability on the Clinical Dementia Rating Scale across all dementia syndromes,
      except for semantic dementia. CONCLUSIONS: This study represents one of the
      largest and most clinically diverse investigations of the ACE-III. Our results
      demonstrate that the ACE-III is an acceptable alternative to the ACE-R. In
      addition, ACE-III performance has broader clinical implications in that it
      relates to carer reports of functional impairment in most common dementias.
      (JINS, 2018, 24, 854-863).

PMID- 30189910
TI  - Sleep Biomarkers, Health Comorbidities, and Neurocognition in Obstructive Sleep
      Apnea.
AB  - OBJECTIVES: Obstructive sleep apnea (OSA) is associated with cognitive impairment
      but the relationships between specific biomarkers and neurocognitive domains
      remain unclear. The present study examined the influence of common health
      comorbidities on these relationships. Adults with suspected OSA (N=60; 53% male;
      M age=52 years; SD=14) underwent neuropsychological evaluation before baseline
      polysomnography (PSG). Apneic syndrome severity, hypoxic strain, and sleep
      architecture disturbance were assessed through PSG. METHODS: Depression (Center
      for Epidemiological Studies Depression Scale, CESD), pain, and medical
      comorbidity (Charlson Comorbidity Index) were measured via questionnaires.
      Processing speed, attention, vigilance, memory, executive functioning, and motor
      dexterity were evaluated with cognitive testing. A winnowing approach identified
      9 potential moderation models comprised of a correlated PSG variable, comorbid
      health factor, and cognitive performance. RESULTS: Regression analyses identified
      one significant moderation model: average blood oxygen saturation (AVO2) and
      depression predicting recall memory, accounting for 31% of the performance
      variance, p<.001. Depression was a significant predictor of recall memory,
      p<.001, but AVO2 was not a significant predictor. The interaction between
      depression and AVO2 was significant, accounting for an additional 10% of the
      variance, p<.001. The relationship between low AVO2 and low recall memory
      performance emerged when depression severity ratings approached a previously
      established clinical cutoff score (CESD=16). CONCLUSIONS: This study examined
      sleep biomarkers with specific neurocognitive functions among individuals with
      suspected OSA. Findings revealed that depression burden uniquely influence this
      pathophysiological relationship, which may aid clinical management. (JINS, 2018,
      28, 864-875).

PMID- 30189911
TI  - Sun behaviour and physical activity associated with autumn vitamin D status in 4
      8-year-old Danish children.
AB  - OBJECTIVE: To explore determinants of serum 25-hydroxyvitamin D (s-25(OH)D)
      during autumn in young, Caucasian children not consuming vitamin D-fortified
      foods or supplements, and explore differences in sun behaviours between pre
      school and school children. DESIGN: In September-October, s-25(OH)D was measured
      by LC-MS/MS; physical activity, sun behaviours and vitamin D intake were assessed
      with questionnaires. SETTING: Baseline data from the ODIN Junior trial at 55
      degrees N. SUBJECTS: Children aged 4-8 years (n 130), of whom 96% gave blood
      samples. RESULTS: Mean s-25(OH)D was 56.8 (sd 12.5) nmol/l and positively
      associated with fat-free mass index (P=0.014). Children being active 6-7 h/week
      had 5.6 (95% CI 1.1, 10.0) nmol/l higher s-25(OH)D than less active children
      (P=0.014). Children seeking shade sometimes or rarely/never had 7.0 (95% CI 1.2,
      12.9; P=0.018) and 7.2 (95% CI 0.8, 13.6; P=0.028) nmol/l higher s-25(OH)D,
      respectively, than children always/often seeking shade. Pre-school children had
      more sun-safe behaviour than school children in terms of use of a hat, sunscreen
      and sunscreen sun protection factor (P<0.05). In school but not pre-school
      children, using a hat rarely/never was associated with 12.1 (95% CI 2.5, 21.7;
      P=0.014) nmol/l higher s-25(OH)D v. always/often (P interaction=0.019). Vitamin D
      intake was not associated with s-25(OH)D (P=0.241). CONCLUSIONS: Physical
      activity and sun behaviours are associated with s-25(OH)D in young children.
      Identifying factors influencing autumn s-25(OH)D is relevant to optimize levels
      before sun exposure diminishes. Strategies to reduce risk of inadequacy should
      consider risk of skin cancer and sunburn, and could include fortification and/or
      vitamin D supplementation.

PMID- 30189912
TI  - Strict sequestration versus lenient isolation precautions during hematopoietic
      stem cell transplant: results of a quality initiative.

PMID- 30189913
TI  - Post-discharge impact of healthcare-associated infections in a developing
      country: A cohort study.

PMID- 30189914
TI  - Constituent analysis of iodine intake in Armenia.
AB  - OBJECTIVE: We sought to assess the universal salt iodization (USI) strategy in
      Armenia by characterizing dietary iodine intake from naturally occurring iodine,
      salt-derived iodine in processed foods and salt-derived iodine in household
      prepared foods. DESIGN: Using a cross-sectional cluster survey model, we
      collected urine samples which were analysed for iodine and sodium concentrations
      (UIC and UNaC) and household salt samples which were analysed for iodine
      concentration (SI). SI and UNaC data were used as explanatory variables in
      multiple linear regression analyses with UIC as dependent variable, and the
      regression parameters were used to estimate the iodine intake sources
      attributable to native iodine and iodine from salt in processed foods and
      household salt. SETTING: Armenia is naturally iodine deficient; in 2004, the
      government mandated a USI strategy. SUBJECTS: We recruited school-age children
      (SAC), pregnant women (PW) and non-pregnant women of reproductive age (WRA).
      RESULTS: From thirteen sites covering all provinces, sufficient urine and table
      salt samples were obtained from 312 SAC, 311 PW and 332 WRA. Findings revealed
      significant differences between groups: contribution of native iodine ranged from
      81% in PW to 46% in SAC, while household salt-derived iodine contributed from 19%
      in SAC to 1% in PW. CONCLUSIONS: Differences between groups may reflect
      differences in diet. In all groups, household and processed food salt constituted
      a significant part of total iodine intake, highlighting the success and
      importance of USI in ensuring iodine sufficiency. There appears to be leeway to
      reduce salt intake without adversely affecting the iodine status of the
      population in Armenia.

PMID- 30189915
TI  - Single cell gene expression analysis identifies chronic alcohol-mediated shift in
      hepatocyte molecular states after partial hepatectomy.
AB  - The analysis of molecular states of individual cells, as defined by their mRNA
      expression profiles and protein composition, has gained widespread interest in
      studying biological phenomena ranging from embryonic development to homeostatic
      tissue function and genesis and evolution of cancers. Although the molecular
      content of individual cells in a tissue can vary widely, their molecular states
      tend to be constrained within a transcriptional landscape partly described by the
      canonical archetypes of a population of cells. In this study we sought to
      characterize the effects of an acute (partial hepatectomy) and chronic (alcohol
      consumption) perturbation on the molecular states of individual hepatocytes
      during the onset and progression of liver regeneration. We analyzed the
      expression of 84 genes across 233 individual hepatocytes acquired using laser
      capture microdissection. Analysis of this single cell data revealed that
      hepatocyte molecular states can be considered as distributed across a set of four
      states irrespective of perturbation, with the proportions of hepatocytes in these
      states being dependent on the perturbation. In addition to the quiescent, primed,
      and replicating hepatocytes, we identified a fourth molecular state lying between
      the primed and replicating subpopulations. Comparison of the proportions of
      hepatocytes from each experimental condition in these four molecular states
      suggested that, in addition to aberrant priming, a slower transition from primed
      to replication state could contribute towards ethanol-mediated suppression of
      liver regenerative response to partial hepatectomy.

PMID- 30189916
TI  - The Role of Nanotechnology in Food Safety: Current Status and Future Perspective.
AB  - Nanotechnology is an emerging science in food production and processing sector,
      yet the role of nanotechnology in food safety has not been comprehensively
      reviewed. This study reviewed the types, sources and mode of actions of the
      nanoparticles used in the food systems. Additionally, the effect of nanoparticles
      on animal health and safety of the products of animal origin was evaluated.
      Moreover, retention of nutritionally important nanoparticle minerals in the
      animal systems and foods of animal origins was analyzed. Furthermore, food safety
      was critically evaluated in terms of antioxidative ability, antibacterial
      properties, and toxicological studies. Finally, the scope of nanoparticle-based
      functional foods and shelf-life enhancement using active packaging was discussed.
      The article concluded that although significant research has been done on the use
      of nanoparticles in food systems, yet commercialization of nanoparticle-based
      foods needs further investigation.

PMID- 30189917
TI  - Recent Progress on Neuromorphic Synapse Electronics: From Emerging Materials,
      Devices, to Neural Networks.
AB  - To realize intelligent functions in electronic devices like a human brain, it is
      important to develop the electronic devices that can imitate biological neurons
      and synapses (synaptic electronics). In this paper, we review the critical
      learning mechanisms for synaptic plasticity. Different electronic devices were
      developed to mimic biological synapses, such as atomic switch, phase change
      memory, ferroelectric memory, and electric-double-layer transistors. More
      importantly, several groups have realized the artificial neuromorphic network
      using multi-gate transistor architecture. The leap from synapse to neuron to
      neural network, thus, has been systematically realized using thin films and
      nanomaterials. The emerging synaptic electronics can have a broader applications
      and brighter future in the next-generation intelligent nano-electronics.

PMID- 30189918
TI  - State of Osseointegrated Titanium Implant Surfaces in Topographical Aspect.
AB  - Titanium is a primary metallic biomaterial widely used in dental implants because
      of its favorable mechanical properties and osseointegration capability.
      Currently, increasing interests have been taken in the interaction between
      titanium implant surface and surrounding bone tissue, particularly in surface
      topographical aspect. There are currently several techniques developed to modify
      surface topographies in the world market of dental implant. In this review, state
      of titanium implant surfaces in topographical aspect is presented from relatively
      smooth surfaces to rougher ones with microtopographies and/or nanotopographies.
      Each surface is summarized with basic elaborations, preparation methods,
      mechanisms for cellular responses and current availabilities. It has been
      demonstrated that rough surfaces evolving from micro- to nano-scale, especially
      hierarchical micro-and nanotopographies, are favorable for faster and stronger
      osseointegration. Further experimental and clinical investigations will aid in
      the optimization of surface topography and clinical selection of suitable
      implants.

PMID- 30189920
TI  - Recent Advances on the Optical Properties of Eu3+ Ion in Nano-Systems.
AB  - Rare-earth (RE) doped nanomaterials have already proven promising materials for
      advanced materials and technologies including optics, lasers, catalysts, alloys,
      magnets, electronics, lighting, bioanalyses, imaging etc. because of their
      outstanding properties such as extremely narrow emission bands, long lifetimes,
      large strokes shifts, photostability and absence of blinking. The efficient of RE
      doped phosphors is found to be controlled by tuning nonradiative relaxation
      pathway which eventually controls by tuning crystal phase of host, lattice
      vibration, concentration of dopant etc. Cross relaxation nonradiative decay due
      to concentration quenching can be manipulated by controlling dopant
      concentration. This review article highlights the optical properties of Eu3+ ion
      in various hosts such as fluoride, phosphate, silica, semiconductor, oxyhalide,
      vanadate, molybdate and tungstate because of its importance for potential
      applications. It is important to know how the host environment influences the
      radiative and nonradiative relaxation which eventually controls the overall
      photoluminescence properties. Of particular attention is how the optical
      properties of Eu3+ ion vary with changing the host environment with the
      anticipation that such knowledge will permit us to construct efficient
      nanomaterials. Finally, a tentative outlook on future advances of this research
      field is given.

PMID- 30189919
TI  - A Review on NanoPCR: History, Mechanism and Applications.
AB  - Polymerase Chain Reaction (PCR) is one of the most common technologies used in
      many laboratories to produce millions of copies of targeted nucleic acid under in
      vitro conditions. However, PCR faces multiple challenges including limited
      availability of DNA in the sample, high GC contents of the template, low
      efficiency, and specificity in amplification. Moreover, some DNA fragments are
      very difficult to amplify due to their secondary structure and high melting
      temperature requirement. To overcome these challenges, many approaches including
      the application of PCR additives in PCR mixture; change in instrument design;
      optimization of PCR system by using the accurate concentration of magnesium ions,
      primers, and cycle number; enzyme modification; and setting up the new touchdown
      and nested PCR strategies have been adopted. Although these approaches have
      enriched the output of PCR, they are not all-purpose and optimization can be case
      dependent. Nanometer-sized materials (nanomaterials) have offered a possible
      solution to these problems as these materials have exceptional physio-chemical
      properties as compared to macroscopic materials. Among these nanomaterials,
      silicon-based materials, carbon-based materials, semiconductor quantum dots
      (QDs), and some metals are well-known PCR enhancer. Hence, new PCR has been
      designed to utilize the unique properties of nanomaterial and is known as
      nanomaterial-assisted PCR or simply nanoPCR. Results of many studies have shown
      that the combination of these nanomaterials and biomolecules can mimic the DNA
      replication process successfully as present in the living organism. In this
      review, we have discussed the role of these different nanomaterials one by one
      and also discussed the mechanisms through which these nanomaterials enhance the
      efficiency of PCR.

PMID- 30189921
TI  - pH-Sensitive DOX-Loaded PAA-PF127-PAA Micelles Combined with Cryotherapy for
      Treating Walker 256 Carcinosarcoma in a Rat Model.
AB  - In this work, a novel combination of drug therapy and cryotherapy for tumor
      treatment was developed. Pluronic F127 modified with poly(acrylic acid) at two
      terminals (denoted as PAA-PF127-PAA) was used as carriers for doxorubicin (DOX)
      delivery. Due to the pH-sensitive property endowed by PAA, the DOX-loaded PAA
      PF127-PAA micelles released DOX faster in the slightly acidic physiological
      environment of the tumor site than that in the neutral physiological environment.
      Three-group rats bearing Walker 256 carcinosarcoma were respectively treated with
      cryotherapy, combination of DOX-loaded micelles and cryotherapy, and saline
      injection to investigate the effect of the combined therapy. The apoptosis rate
      of TdT-mediated dUTP nick-end labeling (TUNEL) slices indicated that compared
      with cryotherapy alone, the DOX-loaded PAA-PF127-PAA micelles combining with
      cryotherapy showed increased apoptosis. Thus, the combination of drug therapy and
      cryotherapy can be used as an effective technique for tumor treatment.

PMID- 30189922
TI  - H727 Multicellular Spheroids and Its Resistance to Antitumor Drugs Sunitinib and
      Axitinib.
AB  - The three-dimensional (3D) culture model of neuroendocrine tumor H727 cells was
      established by using the agarose gel as culture matrix, which provided a new
      method for drug screening of neuroendocrine tumors. As VEGFR inhibitor, sunitinib
      and axitinib were applied to inhibit human neuroendocrine H727 cell line in two
      dimensional (2D) and 3D culture models. The inhibitory rate of H727 cells with
      different drug concentration were assessed by CCK-8 assay method and combined
      with using the FDA/PI double staining and the digital microscope analysis system.
      When the concentration of sunitinib >=4.0 MUmol/L, the H727 spheroids began to
      split, and the apoptosis of H727 cells occurred, the sizes of multicellular
      spheroids was significantly reduced in the groups of high-dose axitinib. These
      results illustrated that sunitinib and axitinib can effectively inhibit the
      growth and proliferation of neuroendocrine tumor H727 cells. Sunitinib and
      axitinib can also promote apoptosis of H727 cells.

PMID- 30189923
TI  - A Novel Method of Synthesis of Fluorescent Carbon Dots for Supersensitive and
      Selective Detection of Cancer Markers.
AB  - Due to the dual role as an electron acceptor and an electron donor in solution,
      carbon dots (Cdots) have broad applications in environmental analysis, biological
      detection, and biosensors. Herein, we report a facile-green strategy for a large
      scale synthesis of fluorescent N, P-doped carbon dots (N, P-Cdots) with an
      absolute quantum yield of 66.08% by a simple one-step thermal decomposition.
      Glucose was selected as a carbon precursor and tryptophan (Trp) as an N-doping
      and passivation reagent. Organic polar solvents with a high boiling point, i.e.,
      ethylene glycol and glycerol, were used as the reaction medium, and phosphoric
      acid was employed as a P source and oxidation accelerator. It is shown that the
      emission wavelength of the N, P-Cdots can be tuned by adjusting the reaction
      conditions, such as mass ratio, heating time, temperature, and medium, without
      further passivation. Finally, advantage was taken of the superior fluorescent
      characteristics of N, P-Cdots to detect selectively and with high sensitivity a
      cancer marker, carcinoembryonic antigen (CEA), based on the fluorescent quenching
      mechanism. Additionally, CEA was also detected in human serum samples with high
      efficiency and RSD, further confirming that the proposed method has a good
      consistency and stability for supersensitive fluorimetric detection of cancer
      markers.

PMID- 30189924
TI  - Development of Magnetic-Fluorescent Bifunctional Drug Delivery System with Dual
      Drug Content and Enhanced Fluorescence.
AB  - The drug delivery system incorporating magnetic particles and fluorescent marker
      would be uniquely effective for magnetic targeting and fluorescent tracing. In
      order for the fluorescent signals to reflect the drug delivery accurately, the
      separation of the fluorescent label and drugs must be counteracted. The objective
      of the current study was to design a method of binding drugs to the fluorescent
      material so that the drug diffusion and delivery could be monitored precisely. To
      obtain fluorescently-labeled drugs, complexes of the rare earth ion with a single
      drug benzimidazole (Tb(Bim)3), and with combined drugs benzimidazole and aspirin
      (TbBim(Asp)2) were generated. Subsequently, the magnetic nanoparticles Fe3O4 and
      TbBim(Asp)2 were encapsulated in chitosan microspheres to prepare magnetic
      fluorescent bifunctional drug delivery system Fe3O4/TbBim(Asp)2/Chitosan. The
      intermediate and final products were analyzed by spectroscopy, X-ray diffraction,
      magnetometry, and electron microscopy, documenting that the newly developed drug
      containing nanoparticles exhibited desirable fluorescent, magnetic, and
      morphologic properties.

PMID- 30189925
TI  - Shear Mode Bulk Acoustic Viscosity Sensor for Blood Coagulation Monitoring in
      Oral Anticoagulant Therapy.
AB  - Frequent monitoring of blood coagulation status is essential for patients
      receiving treatment with some oral anticoagulant agents. In this paper, we
      present a microelectromechanical film bulk acoustic resonator for the measurement
      of blood coagulation parameters. The resonator was made of an aluminum nitride
      piezoelectric film and operated in thickness shear resonance mode with a
      frequency of about 2 GHz. The resonant frequency showed a linear relationship
      with the viscosity of the environmental liquid over the wide range of 1-25 cP,
      falling within the physiological range of human blood. The coagulation process of
      human blood was monitored by following the frequency downshift due to the
      viscosity change. Therefore, the frequency response was used to determine
      quantitatively three clinically significant parameters being the enzymatic
      cascade time, the coagulation time and the clot degree. As a practical
      demonstration, the proposed micro-resonator was applied to monitor coagulation
      for one month in a patient taking the oral anticoagulant, warfarin, daily. The
      results measured by the resonator were consistent with those of the standard
      coagulometer. As a result of the excellent potential for integration,
      miniaturization and the availability of direct digital signals, the shear mode
      film bulk acoustic resonator has promising application for clinical and personal
      coagulation monitoring.

PMID- 30189926
TI  - Extraction of Genomic DNA via Superparamagnetic Fe3O4 Magnetic Colloidal
      Nanocrystal Clusters.
AB  - We herein describe a solvothermal method for preparing superparamagnetic Fe3O4
      magnetic colloidal nanocrystal clusters with an average diameter of 195 nm. The
      Fe3O4 magnetic colloidal nanocrystal clusters were characterized by transmission
      electron microscopy (TEM), dynamic light scattering (DLS) and other methods. The
      Fe3O4 magnetic colloidal nanocrystal clusters were used to extract genomic DNA
      from fresh blood, Gram-negative bacteria, Gram-positive bacteria and frozen
      blood. Results showed that the genomic DNA integrity, purity and yield extracted
      via this universal method were satisfactory. This method is rapid, simple and
      does not use protease K or toxic compounds. This method lays the foundation for
      future research and nucleic acid extraction techniques.

PMID- 30189927
TI  - Synthesis of Fluorescent Nitrogen-Doped Carbon Quantum Dots for Selective
      Detection of Picric Acid in Water Samples.
AB  - In this work, fluorescent nitrogen-doped carbon dots (N-CDs) were pyrolysis
      synthesized using edetic acid and acrylamide as precursors without further
      surface modication. The as-prepared N-CDs were mono-dispersed spherical
      nanoparticles with an average diameter of 3.25 nm. The blue fluorescence emission
      was dependent of the excitation wavelengths, releasing stable and strong blue
      fluorescence under the maximum excitation wavelength. More strikingly, after
      adding picric acid (PA), the fluorescence of N-CDs aqueous solution gave rise to
      the obviously fluorescence quenching due to the inner filter effect. Under the
      optimum conditions, the fluorescence probe can be used for the selective
      detection of PA with a wide linear relationship in the range of 0.01-32 MUM and
      the detection as low as 0.046 MUM. Depending on the fluorescence quenching
      phenomenon, the resultant fluorescent probe for accurate and selective monitor of
      PA in Fenhe river samples was explored. The recoveries fell in the range of
      97.13%-106.21% and the relative standard deviation was below 3% with satisfactory
      results.

PMID- 30189928
TI  - Simultaneous Detection of Hydroquinone and Catechol Using Platinum Nanoparticles
      Decorated Graphene/Poly-Cyclodextrin/Multiwalled Carbon Nanotubes (MWCNTs)
      Nanocomposite Based Biosensor.
AB  - Graphene cyclodextrin prepolymer (pre-CD)-multiwall carbon nanotubes (Gr-CDP
      MWCNTs) nanocomposites modified on glassy carbon electrode (Gr-CDP-MWCNTs/GCE)
      are prepared and then platinum particles (PtNPs) are electrodeposited on it. The
      simultaneous determination of hydroquinone (HQ) and catechol (CC) at PtNPs/Gr-CDP
      MWCNTs/GCE is reported in the present work. Synergistic effect of nanomaterials,
      host-guest chemical reaction ability of CDP, the stacking interaction between
      detected molecules and Gr-MWCNTs surface are considered as the main reasons of
      successfully simultaneous detection of HQ and CC. Cyclic voltammetry (CV),
      scanning electron microscopy (SEM) and different pulse voltammetry (DPV) are
      employed to characterize the proposed PtNPs/Gr-CDP-MWCNTs electrochemical
      biosensor. The prepared PtNPs/Gr-CDP-MWCNTs sensor shows linear response ranges
      of 0.05-27.2 MUM and 0.1-27.2 MUM and have low detection limits (S/N = 3) of
      0.015 MUM and 0.03 MUM for simultaneous electrochemical determination of HQ and
      CC, respectively. It is also applied for the measurement of HQ and CC in local
      river water samples with recoveries from 98.0 to 102.0% and from 99.3 to 101.5%.

PMID- 30189929
TI  - Ultrashort Lipopeptides Self-Assembled with Gold Nanoparticles as Potent
      Antimicrobial Agents.
AB  - To develop new antimicrobial synthetic lipopeptides with optimizing peptide
      length, cationic tripeptides RWR/WRR were N-terminal fatty acylated, and self
      assembled with 1-dodecanethiol-anchored gold nanoparticles (Au-DT NPs) via
      hydrophobic interaction. The ultrashort lipopeptides and their nano-assemblies
      were effective against a variety of microorganisms, with minimal inhibitory
      concentrations ranging from 0.5 to 8 MUg/mL. Hemolysis analysis and in vitro
      cytotoxicity assay revealed that self-assembling with Au-DT NPs would improve
      biological toxicity of lipopeptides, especially for the most active lipopeptides
      (Palmitoyl-RWR, Palmitoyl-WRR) with long lipid tails. As lipopeptides/ Au-DT NPs
      displayed slower bactericidal kinetics compared with free lipopeptides, the mode
      of action was further investigated. Difference in membrane targeting mechanism
      between lipopeptides and their nano-assemblies may be attributed to the
      structural architecture. The simple composition and diverse specificities of
      lipopeptides/Au-DT NPs, as well as their biocompatibility could make them as
      economically available potent antimicrobial agents for various applications.

PMID- 30189930
TI  - Extracellular Biosynthesis, Characterization and Cytotoxic Effect of Silver
      Nanoparticles by Streptomyces coelicoflavus KS-3.
AB  - The present work aimed to investigate extracellular biosynthesis of silver
      nanoparticles (AgNPs) mediated by an actinomycete strain and their cytotoxic
      effects compared with silver ions. The selected strain was identified as
      Streptomyces coelicoflavus KS-3 by phenotypical characteristics and 16S rRNA
      analysis. The formation of biosynthesized AgNPs was proved by an absorption peak
      observed at 437 nm. Transmission electron microscopy (TEM) and dynamic light
      scattering (DLS) analyses revealed that the prepared AgNPs were spherical or
      approximately spherical followed by a small amount of truncated triangular,
      quadrangular and hexagonal with the particle diameters ranging from 2.33 to 91.3
      nm. X-ray diffraction (XRD) pattern confirmed that the AgNPs presented a face
      centered cubic (FCC) structure of crystalline silver. Energy dispersive of X-ray
      (EDX) spectrum and Fourier transform infrared spectroscopy (FTIR) analyses
      verified the existence of biomolecules, such as proteins, that participated in
      the formation and stabilization of AgNPs. Furthermore, the comparative study on
      cytotoxic effect of AgNPs indicated that the AgNPs exhibited higher
      biocompatibility towards human bronchial epithelial (HBE) cells than silver ions
      and exerted potent cytotoxic effect in a dose-dependent manner against human lung
      squamous cell carcinoma cells (HTB-182) and human lung adenocarcinoma cells
      (A549) with the concentrations ranging from 1 to 50 MUg/mL.

PMID- 30189931
TI  - Water-Dispersible Rhodamine B Hydrazide Loaded TiO2 Nanoparticles for "Turn On"
      Fluorimetric Detection and Imaging of Orthosilicic Acid Accumulation In-Vitro in
      Nephrotoxic Kidney Cells.
AB  - Silica (SiO2) is the inevitable form of silicon owing to its high affinity for
      oxygen, existing as a geogenic element perpetrating multifarious health problems
      when bioavailable via anthropogenic activities. The hydrated form of silica viz.
      orthosilicic acid (H4SiO4) excessively displays grave toxicity, attributed to
      prolonged exposure and incessant H+ ions generating capacity inflicting pulmonary
      toxicity and renal toxicity silica. The diverse deleterious potency of silica
      highlights the desirability of selective and sensitive detection of toxic species
      (mainly orthosilicic acid) bioaccumulation in affected living human cells. In
      this paper we have reported, the design of water-dispersible turn-on fluorimetric
      sensing material for the detection of orthosilicic acid in the aqueous phase and
      in live cells. The sensing material was prepared by adsorbing a suitable
      rhodamine derivative (i.e., Rhodamine B hydrazide (Rh1)) on water dispersible
      TiO2 nanoparticles. The function of the sensing system, which is composed of Rh1
      and TiO2 (Rh1@TiO2), is accredited to H+ ion (from orthosilicic acid) induced
      spirolactam ring-opening of the rhodamine derivative generating orange
      fluorescence and bright pink colouration. The sensing system was efficiently
      utilized for fluorimetric detection and imaging of orthosilicic acid accumulation
      in-vitro in human kidney cells (HK cells). To the best of our knowledge, this is
      the first time this sensing system (Rh1@TiO2) is reported for detection of toxic
      silica species accumulation in-vitro in human kidney cells. The advantages, such
      as good water dispersibility, the absence of organic solvents during fluorimetric
      studies, quick turn-on type signal transduction, low-level imaging, which are
      offered by the synthesized sensing material (Rh1@TiO2), make it a potential
      candidate to fabricate medical tool for early identification of silicainduced
      nephrotoxicity, which can help to reduce the burden and risk of chronic kidney
      disease development.

PMID- 30189932
TI  - Induction of FAS II Metabolic Disorders to Cause Delayed Death of Toxoplasma
      gondii.
AB  - The exact mechanism of delayed death of Toxoplasma gondii is not known. FAS II
      synthesis in the apicoplast of T. gondii is essential for the survival of
      Toxoplasma gondii, while beta-hydroxyacylacyl carrier protein dehydratase (FabZ)
      is indispensable for fatty acid synthesis. The present study investigated the
      relationship between the delayed death of T. gondii by inducing metabolic
      disorders due to suppression the expression of FabZ. A tetracycline-induced
      knockout vector inserted with T. gondii fabZ gene was constructed, and
      transfected into T. gondii TATi strain by electroporation. The stable mutants
      with tetracycline-induced knockout were selected, expression of FabZ was
      suppressed by using anhydrotetracycline (ATc), and FAS II deficient tachyzoites
      were prepared. The Western blot and qPCR results revealed that proliferation of
      FAS II deficient tachyzoites was not significantly different compared to the
      normal tachyzoites at 24 h and 48 h; however, after 72 h, the number of T. gondii
      tachyzoites in the ATc treated group was significantly (p < 0.05) less than that
      of non-treated group, indicating the delayed death of T. gondii caused by the
      loss of apicoplast and decrease in the expression of FabZ, which inhibited the
      FAS II metabolism. The results of this study can be used for prevention of
      toxoplasmosis by inducing delayed death of T. gondii.

PMID- 30189934
TI  - Numerical Simulation of Casting Filling Process of Composites Reinforced with
      Nano SiC Based on Smoothed Particle Hydrodynamics.
AB  - The actual casting filling process can be deemed as the coupled flow of air,
      molten metal and solid-phase particles (such as slag) inside the cavity, which
      may cause air entrapment, slag inclusion and other casting defects, and affect
      the quality of casting. Through computation simulation of the casting filling
      process on the basis of smoothed particle hydrodynamics (SPH) method, it can not
      only precisely track the motion trajectories of air, molten metal and slag
      particles, but also precisely predict air entrapment, slag inclusion and other
      casting defects. This paper established a mathematical model of gas-liquid-solid
      three-phase flow for the SPH-based casting filling process. The model eliminated
      the instability of gas-liquid interface pressure by introducing the corrected gas
      liquid two-phase momentum equation, and maintained a clear interface between air
      and molten metal by introducing the surface tension model. In addition, it
      introduced the motion model of rigid body to deal with the coupled flow process
      of slag, air and molten metal. The mathematical model established in this paper
      was used to calculate the bubble floating and the flowing process of the gas
      liquid two-phase during mold filling through the bottom side of the injection
      cavity and of the gas-liquid-solid three-phase flow during mold filling for
      casting of plate (the plate was composite reinforced with nano SiC, and the
      viscosity of the composite melt was calculated from the viscosity formula of the
      composite melt). The calculated results were compared with the experimental
      results to verify the accuracy and validity of the mathematical model
      established.

PMID- 30189933
TI  - Selective Adsorption of Uranium (VI) by Calix[6]arene-Modified Magnetic Graphene
      Oxide.
AB  - Magnetic graphene oxide/calix[6]arene (MGO-C6) composites were prepared and then
      characterized by Fourier transform infrared spectroscopy, Scanning electron
      microscope, X-ray diffraction and Thermo gravimetric analyzer, the adsorption of
      U(VI) by MGO-C6 from aqueous solution was investigated as a function of pH,
      contact time, initial U(VI) concentration and adsorbent dosage. The maximum
      adsorption rate of MGO-C6 can reach up to 93.21%, which was highly efficient for
      the removal of U(VI) under the condition of 1 mg/L initial uranium concentration.
      In addition, the selective adsorption experiment showed that MGO-C6 had an
      overall preference for U(VI). Adsorption process of MGO-C6 fitted well with the
      pseudo-second-order kinetic kinetics and the Langmuir isotherm model. The
      thermodynamic parameters illustrated that the adsorption process was endothermic
      and spontaneous. This work demonstrated that MGO-C6 was a promising adsorbent for
      removal of U(VI) from low concentration uranium-containing wastewater.

PMID- 30189935
TI  - Technology Evolution and Growth Potential for Printed Electronic Papers.
AB  - Electronic paper is now closer than ever to changing the way we read, write, and
      study. This was hailed as a revolution so profound that some see it as second
      only to the invention of the printing press in the 15th century. In this study,
      four analytical methods, which included statistical analysis, technology
      decomposition, multistage technological evolution and growth potential analysis
      were used. Results showed that technological research on business has great
      potential for development and vast market, and it would be another 16 years
      before the limit could be reached for patents. A great deal of technology
      breakthrough has been achieved during 1992 and 2012. The four major countries for
      printed electronic paper development are Japan, USA, South Korea and China.
      However, China has a gap compared with other countries, as the key technology was
      held by large enterprises. The apparatus for printed electronic paper has been
      the major focus in China. The key point for research on printed electronic paper
      was focused on devices for presentation and light emission, and related
      semiconductor devices.

PMID- 30189936
TI  - Effect of Surface-Modified Carbon Nanotubes on Intrinsic Properties and
      Microstructures of Cement Composites.
AB  - Multi-walled carbon nanotubes (MWCNTs) modified by gum arabic (GA) were
      incorporated into cement matrix composites to investigate their effect on
      intrinsic properties. Their ability to disperse the surface-modified MWCNTs
      uniformly in the cement matrix was also assessed using transmission electron
      microscopy (TEM) and energy dispersive spectroscopy (EDS). The intrinsic
      mechanical properties of the cement composites were investigated using Nano
      Indenter. Results showed that the addition of treated nanotubes significantly
      improved the intrinsic properties of cement matrix composites. The porosity and
      pore size distribution of the composites were measured using mercury intrusion
      porosimetry (MIP), and the results indicated that cement paste containing MWCNTs
      had lower porosity and a more uniform pore size distribution. The morphological
      structure of samples was investigated using field emission scanning electron
      microscopy (SEM), thermogravimetric analysis (TGA) and X ray diffraction analysis
      (XRD), which showed that the MWCNTs acted as bridges across cracks and voided and
      formed a network that transferred the load in tension.

PMID- 30189937
TI  - Giant Magneto-Impedance (GMI) Effect in Single-Layer Soft Magnetic Film Under
      Stress.
AB  - The stress-induced magnetic anisotropy can significantly affect giant magneto
      impedance (GMI) effect of the soft magnetic film. This paper is devoted to the
      GMI effect of the single layer soft magnetic film implied without and with a
      stress. By simulating a physical model with MATLAB and COMSOL software, the
      impedance expression of the single layer soft magnetic film and the relation
      between external magnetic field and magnetic permeability are deduced. We
      observed that, without a stress, the sensitive region increased firstly and then
      decreased with the increasing of the excitation current frequency from 1 MHz to
      200 MHz. While the film was subjected to the stress in the direction of the
      current with one end stressed, the stress on the film was gradually reduced from
      stressed end to free end. Also, the impedance change rate of the film changed
      when the stress was added, which is similar to the effect of adding a bias
      magnetic field on the film. More importantly, the addition of stress sigma can
      induce the bias of the GMI measurement range and improve its sensitivity near
      zero magnetic fields. This may provide a new way for designing a GMI sensor with
      higher sensitivity and adjustable measurement range.

PMID- 30189939
TI  - Synthesis of Lanthanide-Ion-Doped NaYF4 RGB Up-Conversion Nanoparticles for Anti
      Counterfeiting Application.
AB  - Well-defined and mono-dispersed lanthanide-ion-doped NaYF4 up-conversion
      nanoparticles (UCNPs) were synthesized via thermal decomposition using lanthanide
      oleate as the precursor. By rational selecting the dopant pairs of the doped
      lanthanide ions (Y3+, Yb3+, Er3+ and Tm3+) with accurate molar ratios, three
      primary-color (RGB) UCNPs which exhibited green (UCNPs-G), blue (UCNPs-B) and red
      (UCNPs-R) fluorescence, respectively, were prepared. The X-ray diffraction (XRD)
      patterns showed that the three UCNPs were purely hexagonal-phase NaYF4 crystals.
      Transmission electron microscopy (TEM) images revealed that the synthesized UCNPs
      exhibited well-defined nanosphere morphology with uniform size distribution. The
      average diameters were 23.95+/-3.35 nm for UCNPs-G, 20.63+/-2.59 nm for UCNPs-B,
      and 19.24+/-2.37 nm for UCNPs-R, respectively. After surface modification
      employing polyacrylic acid (PAA) as modifier, the obtained UCNPs were converted
      to be hydrophilic, which can be used as fillers to construct luminescent polymer
      films and luminescent ink in anti-counterfeiting application.

PMID- 30189938
TI  - Selective Reduction of Nitro Group in Aryl Halides Catalyzed by Silver
      Nanoparticles Modified with beta-CD.
AB  - In this paper, we first report the selective reduction of nitro group in aryl
      halides catalyzed by silver nanoparticles modified with beta-CD. Taking advantage
      of hydrophobic lumen and donor-acceptor behavior of beta-CD, the halogenated
      alkyl groups on the aromatic ring can be enveloped in the inner cavity that
      thereby inhibits the reduction of the halogen. For validating the mechanism
      proposed by us, different silver nanoparticles were applied in parallel
      experiments. In our experiments, UV-vis spectra and NMR spectra were used to
      characterize the selectivity. This strategy represents an outstanding improvement
      on the synthesis of halogenated aromatic amines in comparison with the
      traditional route, and greatly expands the application of silver nanoparticles in
      catalytic field.

PMID- 30189940
TI  - Facile Synthesis of GdF3:Yb3+, Er3+, Tm3+@TiO2-Ag Core-Shell Ellipsoids
      Photocatalysts for Photodegradation of Methyl Orange Under UV, Visible, and NIR
      Light Irradiation.
AB  - To enhance solar energy utilization efficiency, goal-directed design of
      architectures by combining nanocomponents of radically different properties, such
      as plasmonic, upconversion, and photocatalytic properties may provide a promising
      method to utilize the most energy in sunlight. In this work, a new strategy was
      adopted to fabricate a series of plasmonic Ag nanoparticles decorated GdF3:Yb3+,
      Er3+, Tm3+-core@porous-TiO2-shell ellipsoids, which exhibit high surface area,
      good stability, broadband absorption from ultraviolet to near infrared, and
      excellent photocatalytic activity. The results showed that photocatalytic
      activities of the as-obtained photocatalysts was higher than that of pure
      GdF3:Yb3+, Er3+, Tm3+ and GdF3:Yb3+, Er3+, Tm3+@TiO2 samples through the
      comparison of photodegradation rates of methyl orange under UV, visible, and NIR
      irradiation. The possible photocatalytic mechanism indicates that hydroxyl
      radicals and superoxide radical play a pivotal role in the photodegradation.
      Furthermore, the materials also showed exceptionally high stability and
      reusability under UV, visible, and NIR irradiation. All these results reveal that
      core-shell hierarchical ellipsoids exhibit great prospects for developing
      efficient solar photocatalysts.

PMID- 30189941
TI  - Facile Hydrothermal Preparation of Carboxymethyl Chitosan Functionalized
      Hydrotalcite Composite with Enhanced Adsorption Capacity for Cu(II) Ions.
AB  - In order to enhance the adsorption capacity of hydrotalcite material for heavy
      metal ions, the LDH/CMC composite was prepared by a simple hydrothermal method.
      The XRD pattern showed that the presence of CMC has no obvious influence on the
      crystal structure of hydrotalcites. The FT-IR and UV-vis DRS analyses showed that
      the CMC functionalized surface has been obtained. The SEM and BET/BJH showed that
      the morphologies, textural and surface chemical properties of LDH were affected
      remarkably after the introduction of CMC. The weight percentage of CMC in the
      LDH/CMC composite was estimated to be about 17.4%. The adsorption experiments
      showed the LDH/CMC composite exhibited high efficiency in the Cu(II) removal at
      pH > 6.5, affording Cu(II) removal rates of 92.3%. The results demonstrated that
      the LDH/CMC composite was a suitable adsorbent for Cu(II)-contaminated wastewater
      treatment.

PMID- 30189942
TI  - Preparation and Optimization of New High-Power Nanoscale Li4Ti5O12 Full-Cell
      System.
AB  - Lithium ion batteries with graphite negative electrodes have been developed to
      date due to their low power density, which limits their application in many
      cases, however. Nanoscale Li4Ti5O12 has higher power density than conventional
      graphite anode materials. In order to ensure that the full-cell system has high
      power and high energy, cathode materials are very important. In this paper, three
      different cathode materials, LiNi0.8Co0.15Al0.05O2 (NCA), LiNi0.6Co0.2Mn0.2O2
      (NCM622), and LiCoO2 (LCO), were used to conduct a comprehensive study, and
      optimal NCA-Li4Ti5O12(LTO) full battery system was selected under high power
      conditions. On the basis, in order to further increase battery power density, and
      in combination with the mechanism of the supercapacitor non-Faradic energy
      storage, polyaniline activated carbon material (PANI-AC) with excellent
      capacitance characteristics was prepared. In the end, we proposed a new type of
      hybrid battery capacitor system with high power and high energy.

PMID- 30189943
TI  - Study of Electrospinning Parameters and Collection Methods on Size Distribution
      and Orientation of PLA/PBS Hybrid Fiber Using Digital Image Processing.
AB  - The Canny Edge-Based Distance Transform and Hough Transform algorithms were
      successfully implemented to analyze the size distribution and the orientation of
      the electrospun PLA/PBS hybrid fiber. The effect of polymer concentration,
      voltage, feed rate and needle-collector distance were studied. It was found that
      feed rate of 0.5 ml/h and needle-collector distance of 12 cm is required to
      generate smooth and uniform hybrid fibers in the smallest size electrospinning
      with 6 wt.% polymer at voltage of 20 kV. The stationary flat collector with a
      swaying needle and fast rotating drum disc with a stationary needle were used for
      the fiber alignment. In order to improve the size distribution and the
      orientation of the hybrid fibers it is proposed that the fibers should be
      collected on the rotary drum disc at 700 rpm or higher speed.

PMID- 30189944
TI  - A Facile Strategy to Fabricate Nanoscale Zero-Valent Iron Decorated Graphene
      Oxide Composite for Dechloridation of Trichloroacetic Acid in Water.
AB  - In this study, nanoscale zero-valent iron decorated graphene oxide (NZVI/GO)
      composite was fabricated through a reduction process in the presence of sodium
      borohydride (NaBH4) solution. Subsequently, physicochemical properties of the
      NZVI/GO composites were characterized by scanning electron microscope (SEM),
      transmission electron microscopy (TEM), N2 adsorption/desorption, X-ray
      diffraction (XRD), X-ray photoelectron spectroscopy (XPS), Fourier transformation
      infrared spectroscopy (FT-IR) and Raman spectra. Results indicated that Fe
      species existed in the form of Fe0, which uniformly dispersed on the surface of
      GO. Furthermore, the performance of NZVI/GO was evaluated by the degradation of
      tichloroacetic acid (TCAA). TCAA can be rapidly degraded by NZVI/GO. This paper
      provides a promising strategy to synthesize versatile catalyst which would be
      potentially applied in sewage treatment to degrade chlorinated organic compounds.

PMID- 30189945
TI  - Hydrothermal Synthesis of PAA-Coated NaYF4:Yb3+, Er3+ Nanophosphors with
      Predicted Morphology, Phase and Enhanced Upconversion Luminescence Properties.
AB  - In this study, well-defined PAA-coated NaYF4:Yb3+, Er3+ nanophosphors were
      synthesized via a poly(acrylic acid) (PAA) mediated hydrothermal process. The
      rational control of initial reaction conditions, such as hydrothermal
      temperature, pH value of precursor-solution, added amount of PAA, and molecular
      weight of PAA ligand, resulted in upconversion of NaYF4:Yb3+, Er3+ phosphors with
      varying crystal phases (alpha and beta) and morphologies (e.g., nanosphere,
      submicrorod, microrod, microtube, and microprism). By assessing the upconversion
      luminescent properties of the synthesized NaYF4:Yb3+, Er3+ phosphors upon
      excitation by 980 nm infrared light, it was demonstrated that the beta-phase
      NaYF4:Yb3+, Er3+ phosphors generally presented stronger upconversion luminescent
      than alpha-phase NaYF4:Yb3+, Er3+ phosphors and orthorhombic phase of YF3:Yb3+,
      Er3+ sample. Additionally, the beta-phase NaYF4:Yb3+, Er3+ phosphors with hollow
      microtube morphology presented higher upconversion luminescent intensity than
      phosphors of other morphologies. This may be due to microtubes having larger
      surface area (inner and outer surfaces), which promoted the absorption efficiency
      under similar excitation conditions, therefore generating higher luminescent
      intensity. Findings form this study suggest for precisely controlled growth of
      other complex rare earth fluoride compounds and provide a reference for
      exploration of component-, phase- and morphology-dependent upconversion
      luminescence properties.

PMID- 30189946
TI  - Enhanced Visible Light Photocatalytic Decolorization of Methylene Blue by
      Hierarchical Ternary Nanocomposites Cu-TiO2-Mesoporous-Silica Microsphere.
AB  - In this study, hierarchical ternary nanocomposites, i.e., Cu-TiO2-mesoporous
      silica microspheres (Cu-TiO2-MSM), were synthesized as ternary photocatalyst
      system to improve the visible light photocatalytic degradation of the
      environmental pollutant model dye methylene blue (MB). The innovation of this
      method is in situ depositing TiO2 and Cu2O nanoparticles sequentially onto the
      surface of mesoporous silica microspheres to form highly active heterostructure.
      The improved activity for the degradation of MB is attributed to: (1) the high
      adsorption capacity of the porous and interconnected-channel-structure MSM to MB;
      (2) the valence band electrons of TiO2 released from the conduction band
      generating abundant highly active free radicals, which directly reacted with
      adsorbed MB. The photocatalytic degradation efficiency to MB was found to be 98%
      in 5 min, and almost 100% in 20 min. This study paves a way for the development
      of a ternary-doped catalyst for visible light photocatalytic degradation and may
      exhibit widely application in industry.

PMID- 30189947
TI  - Controllable Synthesis of Marks Decahedral Pd Nanoparticles via Etching.
AB  - Marks decahedral nanoparticles have attracted significant attention in recent
      years. In this work, a method of synthesizing Marks decahedron via etching
      regular decahedral nanoparticles is proposed and verified by Pd nanoparticles,
      which shows a high yield of Marks decahedron. The present work suggests that one
      can tune the concave size of Marks decahedral via controlling the etching time
      and the amount of Poly(vinyl pyrrolidone) (PVP). The thermal stability of Marks
      nanoparticles is explained by Bond-Energy model, which predicts the largest
      groove to be the most stable configuration. Moreover, the present method can be
      extended to synthesize Marks decahedral nanoparticles of other elements, and is
      of great significance for further studies and applications of Mark decahedral
      nanoparticles.

PMID- 30189948
TI  - Size-Dependent Effect of Cu2O Nanocubes in Electrochemical and Photocatalytic
      Properties.
AB  - Cu2O nanocubes with different size (ranging from 20 nm to 400 nm) were prepared
      by a seed-mediated method to systematically explore the strong size-dependent
      properties in photocatalytic degradation of methyl orange (MO). Cu2O nanotubes
      were characterized by TEM, XRD, UV-Vis measurements. The size-dependent
      photocatalytic efficiency of the Cu2O nanocubes was evaluated by degradation of
      methyl orange (MO) in water under visible light (lambda > 420 nm) irradiation.
      Furthermore, the photocurrent, linear sweep voltammetry (LSV) and electrochemical
      impedance spectra (EIS) measurements were applied to elucidate the size-dependent
      properties of Cu2O nanocubes, which demonstrated that smaller Cu2O nanocubes with
      certain length (30 nm) showed higher current density, faster electron transfer
      and lower rate of charge recombination in their exposed (100) facet. Therefore,
      30 nm Cu2O nanocubes showed stronger visible light absorption capacity and higher
      photocatalytic activity in MO degradation among a series of nanocubes (20, 30,
      100, 130, 200 and 400 nm) and their corresponding photocatalytic activities
      decreased with increasing the particles sizes.

PMID- 30189949
TI  - One-Step Pyrolysis Transformation of Mulberry Leaves Followed by Electrochemical
      Treatment: Preparing of M (M = Pt, Au) Nanoparticles Incorporated Nitrogen-Doped
      Carbon Nanoporous Structures as Efficient Electrocatalyst for Hydrogen Evolution
      Reaction.
AB  - To facilely develop low-cost and efficient hydrogen evolution electrocatalysts,
      catalyst with low content of platinum on nitrogen-doped carbon nanoporous
      structures were prepared for hydrogen evolution reaction (HER). This study
      firstly demonstrated the one-step pyrolysis transformation of conveniently
      accessible mulberry leaves to obtain nitrogen-doped nanoporous carbons (N-NPCs)
      for hydrogen evolution reaction. After electrochemical treatment, the obtained N
      NPCs-ET with Pt as counter electrode exhibited an unexpected high hydrogen
      evolution activity, which had low onset overpotential of 100 mV and a Tafel slope
      of 60 mV dec-1. N-NPCs-ET maintained catalytic activity for at least 10 h in 0.5
      M H2SO4 solution. The enhanced HER performance was relevant to the incorporation
      of Pt nanoparticles, which were dissolved from anodic Pt counter electrode in
      acid media and precipitated into cathodic N-NPCs surface again. Moreover, for the
      first time, we found that with a gold electrode as the counter electrode, Au
      nanoparticles could be incorporated into N-NPCs by electrochemical treatments and
      the formed Au nanoparticles decorated N-NPCs possessed efficient catalytic
      activity toward HER.

PMID- 30189950
TI  - Platinum-Copper Bimetallic Alloy Nanoflowers as Efficient Electrocatalyst for the
      Methanol Oxidation Reaction.
AB  - Special morphological noble metal-based bimetallic alloy nanostructures became
      popular for methanol oxidation reaction in order to reduce the high cost of the
      Pt catalyst and improve the catalyst activity. Herein, we developed a facile one
      pot hydrothermal method for the synthesis of platinum-copper bimetallic
      nanoflowers (Pt-Cu NFs) in the presence of hexadecyl trimethyl ammonium bromide
      (CTAB). The morphology, structure and composition of Pt-Cu NFs were carefully
      characterized and the synthesized parameters were optimized systematically by
      adjusting different experimental conditions. Results showed that the CTAB usage
      and the NaI amount were critical to the controlled synthesis of Pt-Cu NFs. The Pt
      Cu NFs were high-performance electrocatalysts for the methanol oxidation reaction
      (MOR) with superior activity and superior stability in alkaline solution, which
      were far better than pure Pt nanoparticle electrocatalysts.

PMID- 30189951
TI  - Uniform and Well-Dispersed LuBO3 Hollow Microspheres: Synthesis, Formation and
      Photoluminescence Properties.
AB  - A hard template strategy is developed to fabricate the LuBO3: Eu3+/Tb3+ hollow
      microspheres using a novel multi-step transformation synthetic route for the
      first time with polystyrene (PS) spheres as the template, followed by the
      combination of a facile homogeneous precipitation method, an ion-exchange
      process, and a calcination process. The results show that the as-obtained LuBO3:
      Eu3+/Tb3+ hollow spheres have a uniform morphology with an average diameter of
      1.8 MUm and shell thickness of about 80 nm. When used as luminescent materials,
      the emission colors of LuBO3: Eu3+/Tb3+ samples can be tuned from red, through
      orange, yellow and green-yellow, to green by simply adjusting the relative doping
      concentrations of the activator ions under the excitation of ultraviolet (UV)
      light, which might have potential applications in the field such as light display
      systems and optoelectronic devices.

PMID- 30189953
TI  - A Numerical Study of the Effects of Nano-Biological Scaffolds on Inflammatory
      Vascular Wall.
AB  - This research investigated the effect of different nano-biological scaffolds on
      blood vessel walls by numerical analysis. The dynamics behavior of fluids and the
      mechanical property of vessel wall were studied when the blood vessel wall was in
      the state of inflammation. Employing straight and bent blood vessels as 3D
      models, this research simulated the blood flow in the inflammatory blood vessels
      and put forward the mathematical method to analyze mechanical characteristics of
      the vessel walls under the condition of the bi-directional coupling. At the same
      time, the impact of the nano-biological scaffolds was explored. The results
      showed that the thrombus in the inflammatory blood vessels significantly
      influenced the dynamics behavior of blood fluids. The blood velocity in the
      rectangular mesh nano-biomaterials was greatly decreased. It concluded that the
      numerical method was feasible to estimate signal feedbacks. Simulating the fluid
      dynamics behavior in the inflammatory blood vessels, the mechanical
      characteristics of the vessel wall under the condition of the two-way coupling
      was consistent with the medical facts. Moreover, the clogging degree had
      significantly influence on the inflammation of vessel wall. These findings
      facilitated health care workers to employ proper nano-biological scaffolds in the
      thrombosis treatment.

PMID- 30189952
TI  - Multiple Silver Nanoparticles Anchored Hollow Mesoporous Silica Nanospheres by
      Polyacrylic Acid Aggregate Templating Approach for Catalytic Reduction of p
      Nitrophenol.
AB  - Anchoring metal cores inside porous shells can endow metal catalyst with high
      selectivity and stability. Herein, multiple silver nanoparticles were
      successfully anchored in hollow mesoporous silica nanospheres (Ag@HMSNs) through
      a facile one-pot method. Polyacrylic acid aggregates self-assembled in
      water/ethanol solvent were used as core templates and Ag nanoparticles captors,
      and hexadecyl trimethoxysilane (C16TMS) was used as the pore-making agent. The
      hollow cavity, encapsulated multiple Ag nanoparticles, and mesoporous silica
      shell of the Ag@HMSNs were confirmed by X-ray powder diffraction (XRD),
      transmission electron microscopy (TEM), and nitrogen sorption analysis. Just as
      expected, Ag nanoparticles (2-5 nm) were encapsulated in the cavity of hollow
      mesoporous silica nanospheres with the size of about 200 nm. The fabricated
      Ag@HMSNs showed excellent performance for catalytic reduction of p-nitrophenol (4
      NP). Also, catalytic activity of the Ag@HMSNs for 4-NP reduction was increased
      with the addition amount of the pore-making agents and surface areas. The
      superior catalytic performance was attributed to the unique structural features
      of Ag@HMSNs architecture, in which the mesoporous shell provided readily
      accessible pathway for fast transport of reactants to the encapsulated Ag
      nanoparticles.

PMID- 30189954
TI  - Effects of TiO2 Nanofluid on the Surface State of Brass.
AB  - The surface states of brass in simulated cooling water (SCW) containing or free
      of sodium dodecyl benzene sulfonate (SDBS) and TiO2 nanofluid were analyzed by
      means of scanning electron microscope (SEM), energy spectrum analysis (EDS) and X
      ray diffraction (XRD). The concentrations of Cu and Zn ions in the solution after
      brass immersion were analyzed using a plasma emission spectrometer. The
      relationship between the surface states and corrosion resistance of brass was
      investigated by electrochemical impedance spectroscopy (EIS). The results showed
      that the brass surface was mainly covered with zinc compound Zn5(OH)6(CO3)2 as
      corrosion product in SCW. In SCW containing SDBS, a large amount of SDBS was
      adsorbed on the brass surface. In TiO2 nanofluid, the brass surface was
      relatively bare and mainly contained cuprous oxide. There was no obvious adhesion
      of SDBS aggregates and no accumulation of zinc compound on brass surface in TiO2
      nanofluid. TiO2 nanoparticles inhibit the adsorption of SDBS on brass surface.
      Solution analysis results showed that the concentrations of Cu and Zn ions in
      TiO2 nanofluid was obviously higher than that in SCW and SCW containing SDBS,
      indicating that most of corrosion products of brass dissolved into the nanofluid.
      The EIS results illustrated the brass electrode had a larger reaction resistance
      in SCW containing SDBS, indicating the good protective performance of the
      adsorbed SDBS film on brass surface. The reaction resistance of the brass
      electrode was the smallest in TiO2 nanofluid, which illustrated that TiO2
      nanoparticles in solution promoted the corrosion of brass.

PMID- 30189955
TI  - Influence of Al2O3 Nanoparticles on Corrosion Inhibition Performance of
      Benzotriazole to Brass.
AB  - The influence of Al2O3 nanoparticles on corrosion inhibition of benzotriazole
      (BTA) in brass/ simulated water system was studied by potentiodynamic
      polarization curve and electrochemical impedance spectroscopy (EIS). The results
      show that BTA has good corrosion inhibition effect on brass. Al2O3 nanoparticles
      could reduce the corrosion inhibition performance of BTA. The higher the
      concentration of Al2O3 nanoparticles in simulated water, the lower corrosion
      inhibition performance of BTA. The isothermal adsorption of BTA on brass surface
      in simulated water and Al2O3 nanofluids was analyzed. The results indicated that
      the adsorption of BTA on brass surface followed the Langmuirs' adsorption
      isotherm, the adsorption Gibbs free energy DeltaG was less than -40 kJ/mol,
      corresponding to chemical adsorption, in both simulated water and Al2O3
      nanofluids. The -DeltaG value of BTA on brass surface decreased in Al2O3
      nanofluids, indicating the weakening of the BTA adsorption on the brass surface.
      Surface analysis of brass samples by optical microscope and X-ray diffraction
      confirmed the above results.

PMID- 30189956
TI  - A Study on the Structure and the Photoelectrical Properties of the Al-Doped ZnO
      Thin Films by Atomic Layer Deposition in Low Temperatures.
AB  - The AZO transparent conductive films are prepared by the atomic layer deposition
      (ALD) at a low temperature of 150  degrees C. The different Al-Zn doping ratios
      were designed during the deposition. The phase structure of the films was
      characterized by XRD, the electrical properties of thin films were analyzed by
      the Holzer test, and the optical properties of thin films were analyzed by the UV
      3600 (UV-VIS-NIR) spectrophotometer. The results showed that all the films
      preferred the orientation of the C axis during the growth process, the AZO films
      have a very low resistivity of 6.955*10-4 Omega.cm with the Al doping ratio by
      2%, the deposition temperature is 150  degrees C and the thickness of the film is
      200 nm. The transmission of AZO films with the different doping ratios in the
      visible region is 85%. The proper doping ratio can be selected to get the
      excellent photoelectric properties of AZO thin films. Such low resistivity AZO
      transparent conductive film is expected to replace the ITO as the transparent
      electrode for the organic light-emitting devices and the other new generation of
      the optoelectronic devices.

PMID- 30189957
TI  - Ultralong TiO2 (B) Nanowires/TiO2 Nanoparticles Composites for Rapid Electron
      Transport in Dye-Sensitized Solar Cells.
AB  - The relatively small electron diffusion coefficient and high charge recombination
      rate of TiO2 nanoparticle (NP) film limit charge collection in TiO2 NP based dye
      sensitized solar cells (DSSCs). Herein, ultralong bending TiO2 (B) nanowires
      (NWs) were introduced to TiO2 NP photoanode and expected to modify electron
      transport of DSSCs. The TiO2 (B) NWs/TiO2 NP composite structure was prepared by
      a facial process combining the stirring hydrothermal method with mechanical
      mixing method. When the composite structure was applied to DSSCs, the rapid
      electron transport pathway was formed in photoanode, which was clarified by the
      small electron transport resistance and long electron diffusion length, improving
      the charge collection efficiency. Moreover, the scattering effect of TiO2 (B) NWs
      could enhance the light harvesting, and thus improve the power conversion
      efficiency (PCE) of DSSCs. The excellent electronic and optical characteristics
      of TiO2 (B) NWs yield the maximum enhancement of PCE (36.4%) when 50% (wt.%) TiO2
      (B) NWs was integrated into TiO2 NP based DSSC. The work provides new insights
      into the design and tailoring nanowires to enhance the PCE of DSSCs for practical
      applications.

PMID- 30189958
TI  - Graphene Oxide Affects Growth and Resistance to Sclerotinia sclerotiorum in
      Brassica napus L.
AB  - Researchers have shown that graphene oxide has a significant effect on plant and
      pathogen growth and development. To better understand the effect of graphene
      oxide on the resistance of Brassica napus L. to Sclerotinia sclerotiorum,
      Zhongshuang 11 was used to evaluate changes in the morphology and physiology
      after graphene oxide treatment. Detached leaf inoculation was used to detect S.
      sclerotiorum infection in rapeseed. The results indicated that treatment with a
      low concentration of graphene oxide had no significant effect on the growth of B.
      napus "Zhongshuang 11." Graphene oxide inhibited S. sclerotiorum in PDA medium.
      Treatment with 15 mg/L graphene oxide for 8-24 h in seeds and 8-16 h in seedlings
      suppressed S. sclerotiorum growth compared to the control samples. These results
      demonstrate that a low concentration of graphene oxide did not harm the growth of
      B. napus but did enhance its resistance to S. sclerotiorum.

PMID- 30189959
TI  - High-Performance Supercapacitors Based on E-MnO2/RGO Fiber Electrodes for
      Wearable Energy Storage.
AB  - Hybrid fibers based on MnO2/reduced graphene oxide have been fabricated for
      flexible energy storage devices. Graphene oxide nanoflakes were reduced in a
      polytetrafluoroethylene (PTFE) pipeline under the appropriate condition to
      develop a fiber current collector, which also provides the possibility of
      weaving. The RGO fiber with the radius of about 35 MUm has a resistance of 150
      Omega . cm. MnO2 nanoflakes directly grow on the RGO fiber surface acting as the
      electrode material of the device. The MnO2/RGO hybrid fibers provide excellent
      energy storage performances. The as-fabricated SC exhibits a high areal
      capacitance of 1.37 F.cm-2 at the scan rate of 1 mV.s-1, and outstanding long
      term cycling stability of 93.75% retention after 5000 cycles. This work
      demonstrates a cost-effective and versatile strategy for wearable energy storage
      devices.

PMID- 30189960
TI  - Preparation and Characterization of Bi2Ti2O7 Pyrochlore by Acetone Solvothermal
      Method.
AB  - In this study, we reported a novel synthesis route of Bi2Ti2O7 pyrochlore by
      acetone solvothermal method. The bismuth nitrate and tetrabutyl titanate were
      used as reactant, and acetone was used as solvent. XRD patterns showed that the
      pure Bi2Ti2O7 particles were synthesized when the molar ratio of Bi/Ti was
      between 0.4 and 0.8. The SEM showed that the Bi2Ti2O7 crystal was uniform
      spherical particles. The carboxylic acid produced in the reaction system may be
      the main factor of bismuth mineralization. Compared with TiO2, pure Bi2Ti2O7
      photocatalyst exhibited superior photocatalytic activity for methyl orange (MO)
      and tetracycline hydrochloride (TC) under simulated solar light. The possible
      formation mechanism was proposed.

PMID- 30189961
TI  - Ordered Silica Nanosphere Templates: Large-Area Assembly and Characterization.
AB  - Ordered silica nanosphere templates, which are usually known as colloidal
      crystals, are most widely used to prepare ordered porous nanostructure materials
      among the templates to fabricate nanostructure materials. We present here a
      method for the simultaneous assembly of multiple ordered silica nanosphere
      templates with same quality, in which a glass trough together with a stand was
      used as the experimental cell. Two different diameters of silica colloidal
      particles were selected for our experiments, namely ~190 nm and ~280 nm. The
      growth process, thickness and optical properties of films of silica nanospheres
      on substrates were studied. The particle sedimentation and solvent evaporation
      both play a role in determining particle volume fractions. In addition, the
      standard deviation of the diameter of the particles affects the optical
      properties of the films along the growth direction. There was almost no
      difference observed in our measurements of the film thickness and optical
      properties for both the same regions of different films and different regions of
      the same film along the direction perpendicular to the growth direction. The
      elucidation of the growth process and characterization of the film properties
      achieved in this study could help us to obtain better quality templates. This is
      the first systematic study of the evolution of the thickness and optical
      properties of ordered silica nanosphere films formed by a simultaneous assembly
      process.

PMID- 30189962
TI  - A Multi-Frequencies Micro-Electromagnetic Vibration Energy Harvester with
      Nonlinearity for Expanding the Frequency Band.
AB  - In this paper, we proposed a multi-frequencies electromagnetic vibration energy
      harvester (EVEH) with a wider operating frequency band. The EVEH contains three
      different vibration picking-up systems with different natural frequencies. A
      broadened bandwidth was obtained by combining the structural nonlinearity of the
      vibration picking-up systems with the multi-frequencies, while the vibration
      energy harvest was increased by adopting two induction coils in the EVEH system.
      At an acceleration of 1.5g and frequencies of 45.6, 75 and 146.5 Hz, the peak
      peak voltages of the prototype were 336, 270 and 39.8 mV, respectively. The
      corresponding bandwidths were 10.1, 7.8 and 4.2 Hz, respectively.

PMID- 30189963
TI  - Laser Structuring of Underwater Bubble-Repellent Surface.
AB  - Bubbles in aqueous media are pervasive and unavoidable. However, underwater gas
      bubbles adhesion to the metal pipework can sometimes seriously damage the surface
      and reduce the useful life of devices. Herein, we report a simple way to
      fabricate underwater bubble-repellent surface by one-step femtosecond laser
      direct writing technology. The as-prepared surface exhibits superhydrophilicity
      in air and superaerophobicity in water, and the bubble contact angles reach 159+/
      2.5 degrees  in water. The surface presents ultralow bubble adhesion, and the
      rolling angle of the bubble is small. The potential mechanism is also discussed.
      This method offers an easy route to prepare underwater superaerophobic surfaces
      with ultralow bubble adhesion, and it has potential applications in underwater
      bubble-repelling facilities.

PMID- 30189964
TI  - Green Synthesis of Silver Nanoparticles Using Jurinea dolomiaea and Biological
      Activities.
AB  - Green syntheses of nanoparticles using plant materials are of tremendous scope.
      Here we report advantageous green synthesis for silver nanoparticles (AgNPs)
      using aqueous-root extract of Jurinea dolomiaea and AgNO3. Color change of
      solution and UV-Vis absorption at 444 nm indicated the formation of AgNPs. XRD
      confirmed their face centered cubic structure (fcc) with average particle size of
      24.58 nm. SEM analysis showed their spherical, cubic and triangular structures.
      FT-IR indicated the presence of functional groups of reducing and stabilizing
      phytochemicals. Methanol-root extract of J. dolomiaea revealed high flavonoid
      (445 mg RE/g) and phenolic contents (92 mg GAE/g). Methanol-extract showed high
      antioxidant potency (IC50 = 0.494 MUg/mL), rationally due to its high phenolic
      and flavonoid contents. These AgNPs showed the highest and equal antimicrobial
      activities against Escherichia coli and Pseudomonas aeruginosa (Inhibition zone
      11.0 mm) whereas, methanol-roots extract showed equal and intermediate activities
      (Inhibition zone 8.0 mm) against both pathogens but aqueous extract showed poor
      activities (Inhibition zone 6.0 mm) against these both pathogens. AgNPs are
      playing a major role in the field of nanotechnology and nanomedicine due to their
      antimicrobial and drug delivery efficacy as well as reasonable tolerance in human
      biology.

PMID- 30189965
TI  - Biogenic Synthesis of AgNPs with Saussurea lappa C.B. Clarke and Studies on Their
      Biochemical Properties.
AB  - Nanotechnology has become an irreplaceable need and green synthesis of
      nanoparticles offers several advantages over physical and chemical methods.
      Medicinal plants are the main reservoirs of drugs and drug candidates. We report
      the biogenic synthesis of silver nanoparticles (AgNPs) using aqueous root extract
      of Saussurea lappa. Verification and characterization of these nanoparticles were
      done by UV-visible spectroscopy, XRD-analysis and Scanning Electron Microscopy
      and FT-IR. Extract-loaded-AgNPs showed the highest inhibition zone against
      Escherichia coli (11.0 mm) and intermediate against Pseudomonas aeruginosa (9.0
      mm). The methanolic root extract of S. lappa alone, also moderately inhibited
      Pseudomonas aeruginosa (9.0 mm) and showed lower activity (6.0 mm) against
      Escherichia coli. Its aqueous roots extract inhibited (6.0 mm) the growth of
      tested organisms. Methanolic extract showed antioxidant potency (IC50 = 0.814
      MUg/mL). Experiments revealed the presence of phenols and flavonoids in the roots
      of Saussurea lappa. These findings provide promising interest to exploit
      Saussurea lappa for the biogenic synthesis of AgNPs and their biological
      applications.

PMID- 30189966
TI  - Ultraviolet Photodetector Based on ITO/MgO/ZnO Structure Grown by Hydrothermal
      Process.
AB  - A simple two-step aqueous method was employed to grow MgO nanostructures on
      ZnO/sapphire at low temperature. The obtained thin MgO nanostructures were
      uniformly distributed on the surface of ZnO layer and showed the sheet-like
      structures. Meanwhile, an ultraviolet (UV) photodetector based on ITO/MgO/ZnO
      structures was fabricated by simple way. The obtained UV detector showed
      excellent UV sensing properties. This novel method will greatly facilitate
      fabrication of large-scale metal-insulator-semiconductor with relatively low cost
      at remarkably low temperature.

PMID- 30189967
TI  - Research on the Properties of Solid Oxide Fuel Cells Based on Composite Cathode
      of YBaCo1.4Cu0.6-O5+delta-xSDC.
AB  - The new type of cathode material YBaCo1.4Cu0.6-O5+delta-xSDC (x = 20, 30, 40, 50
      wt.%) was synthesized by sol-gel method, electrolyte material of Ce0.8Sm0.2O1.9
      (SDC) and La0.9Sr0.1Ga0.8Mg0.2O3-delta (LSGM) were synthesized by glycine
      combustion, composite cathode materials were prepared by mixing the two materials
      evenly. The performance was analyzed using the ac impedance spectrum and SEM, the
      best performance was obtained with the ratio of x = 30%. After 2 hour sintering
      at 950  degrees C, YBCC-30%SDC cathode polarization resistance are 0.027 Omega .
      cm2, 0.043 Omega . cm2 and 0.074 Omega . cm2 at 850  degrees C, 800  degrees C,
      750  degrees C, respectively. The performance of single battery YBCC
      30SDC/LSGM/SDC/NiO-SDC was tested and the power density reached its maximum of
      662 mW/cm2 at 850  degrees C.

PMID- 30189968
TI  - Study on the Fabrication of White Organic Light-Emitting Devices Using the Doping
      Characteristics of Rubrene and Programmed Test Circuit.
AB  - A white organic light emitting device with structure of ITO/2T
      NATA(20)/NPBX(15)/DPVBi(15)/ Alq:Rub(10, x)/Alq3(40)/LiF/Al was fabricated using
      doping rubrene. When the concentration of rubrene is 3 wt.%, the chromaticity is
      the best (0.319, 0.317), and the color coordinates are stable. When the thickness
      of the doping layer is 20 nm, the efficiency and luminance of the devices are the
      highest, which are 5.1022 cd/A and 17130 cd/m2, respectively. On the basis, a
      test system is consisted of Solomon's OLED display control driver chip SSD1306
      and microcontroller AT89C52, which tests the OLED dot matrix through the program
      to determine whether the matrix has dead point. Through experimental comparison,
      the test results are consistent with the external power supply test. The system
      has the characteristics of high efficiency and display characters of dynamic and
      static pictures, which provides a feasible driving method for the practical
      application of OLED.

PMID- 30189969
TI  - Assessments of Different Methods for Testing Heteroresistance to Rifampicin in
      Tubercle Bacillus.
AB  - This study was undertaken to compare the ability of four clinically used methods
      to detect the heteroresistance of the tubercle bacillus to Rifampicin (Rif). A
      total of 94 sputum smear-positive samples of re-treated tuberculosis (TB)
      patients were employed. Rif-resistant tubercle bacillus tests were carried out by
      four methods: Lowenstein-Jensen cultures (L-J), reverse transcription-polymerase
      chain reaction (RT-PCR), microscopic observation drug susceptibility (MODS), and
      high-resolution melting (HRM). The rates of detection of Rif-resistant bacteria
      by of L-J, RT-PCR, MODS, and HRM were 35.1% (33), 36.4% (35), 36.2% (34), and
      16.0% (15), respectively. The rate of detection by RT-PCR was slightly higher
      than that of L-J and MODS (P > 0.05) and significantly higher than that of HRM (P
      < 0.01). The median detection time of L-J, RT-PCR, MODS, and HRM was 60 d, 1 d, 9
      d, and 1 d, respectively. Smear-positive TB can be directly and rapidly detected
      using RT-PCR and MODS technologies. The positive rates of RT-PCR and MODS were
      not only highly consistent with that of L-J and remarkably higher than that of
      HRM, but also were obtained in a markedly shortened time. The combination of MODS
      and RT-PCR has a synergistic effect on the speed of detection of
      heteroresistance, which is of great value for the timely and accurate diagnosis,
      guiding the clinicians in formulating the optimal treatment of smear-positive
      pulmonary tuberculosis.

PMID- 30189970
TI  - Effects of Continuous Phase and Crosslinking Agent on the Rheological Behaviors
      and Properties of Cationic Poly(urethane-acrylate) Emulsifier-Free
      Microemulsions.
AB  - Cationic poly(urethane-acrylate) emulsifier-free microemulsions are prepared by
      seeded emulsion polymerization (SPUA) or in-situ emulsion polymerization (IPUA)
      with (a) or without (b) crosslinking agent hydroxyethyl acrylate (HEA).
      Furthermore, no surfactant is introduced into the reaction system. The effect of
      continuous phase and HEA on the rheological behavior and properties of
      microemulsions are studied. The results show that IPUA using vinylmonomers as the
      continuous phase and with HEA (IPUAMB-b) has the highest zeta value, lowest
      coagulation ratio, smallest particle size of 48 nm and apparent core-shell
      structures. Rheological research has concluded that the zero-shear viscosity of
      IPUAB-b and IPUAM-b emulsion is 6.03*102 and 7.89 Pa.s, respectively, and
      presents pseudoplastic behavior. However, IPUAMB-b and SPUA-b display Newtonian
      behavior with eta0 of 0.136 Pa.s and 0.0823 Pa.s, respectively. PUA emulsions
      display similar rheological behavior when NMP is replaced by the mixture of MMA
      and BA.

PMID- 30189972
TI  - Effect of Crystallization on the Catalytic Cracking Performance of Zeolite Socony
      Mobil-5.
AB  - In the research, zeolite socony mobil-5 (ZSM-5) catalyst was prepared by
      hydrothermal method and characterized by X-ray powder diffraction (XRD), scanning
      electron microscopy (SEM), transmission electron microscopy (TEM), NH3
      temperature programmed desorption (NH3-TPD) and Brunauer- Emmett-Teller (BET).
      The catalytic products from Jatropha carcass L. oil were analyzed by gas
      chromatography-mass spectrometer (GC-MS). The effects of crystallization time and
      crystallization temperature on catalytic cracking performance of ZSM-5 were
      investigated. According to the results, the catalytic cracking performance of ZSM
      5 was closely associated with its pore structure. When the crystallization time
      was 60 h and the crystallization temperature was 170  degrees C, ZSM-5 with
      optimal catalytic cracking performance was synthesized. Catalyzed by the optimal
      ZSM-5, Jatropha carcass L. oil showed the liquid conversion rate of 26.60% and
      the acid value of 1.24 mg KOH.g-1. The main catalytic products from Jatropha
      carcass L. oil included benzene (10.02%), methylbenzene (20.52%), o-xylene
      (14.45%) and p-xylene (6.59%).

PMID- 30189971
TI  - Different Crystal Form Titania Supported Ruthenium Nanoparticles for Liquid Phase
      Hydrodeoxygenation of Guaiacol.
AB  - Titania supported Ruthenium-based catalysts were prepared for liquid phase
      hydrodeoxygenation of guaiacol to cyclohexanol. The catalytic performance is
      affected by the different crystal forms of titania supports. Anatase and rutile
      titania supported catalyst 5%Ru/a-r-TiO2 presents higher BET surface area, better
      dispersion of Ru particles with smaller particle size of 3-4 nm, more acidic
      centers, and more Rudelta+ located at the boundary between anatase titania and
      rutile titania. Hence, 5%Ru/a-r-TiO2 gives the best catalytic performance of
      95.33% conversion of guaiacol and 79.23% selectivity to cyclohexanol, other
      products mainly include cyclohexane, benzene, cyclohexanone and 1,2
      cyclohexanediol. Based on the results of this work, the possible reaction path
      for guaiacol hydrodeoxygenation was proposed.

PMID- 30189973
TI  - The Effect of Ambulance Response Time on Survival Following Out-of-Hospital
      Cardiac Arrest.
AB  - BACKGROUND: Out of hospital cardiac arrest (OHCA) is one of the more common
      causes of death in Germany. Ambulance response time is an important planning
      parameter for emergency medical services (EMS) systems. We studied the effect of
      ambulance response time on survival after resuscitation from OHCA. METHODS: We
      analyzed data from the German Resuscitation Registry for the years 2010-2016.
      First, we used a multivariate logistic regression analysis to determine the
      effect of ambulance response time (defined as the interval from the alarm to the
      arrival of the first rescue vehicle) on the hospital-discharge rate (in percent),
      depending on various factors, including resuscitation by bystanders. Second, we
      compared faster and slower EMS systems (defined as those arriving on the scene
      within 8 minutes in more than 75% of cases or in <= 75% of cases) with respect to
      the frequency of resuscitation and the number of surviving patients. RESULTS: Our
      analysis of data from a total of 10 853 patients in the logistical regression
      model revealed that the rate of hospital discharge was significantly affected by
      the ambulance response time, bystander resuscitation, past medical history, age,
      witnessed vs. unwitnessed collapse, the initial heart rhythm, and the site of the
      collapse. The success of resuscitation was inversely related to the ambulance
      response time; thus, among patients who did not receive bystander resuscitation,
      the discharge rate declined from 12.9% at a mean response time of 1 minute and 10
      seconds to 6.4% at a mean response time of 9 minutes and 47 seconds. Twelve
      faster EMS systems and 13 slower ones were identified, with a total of 9669 and
      7865 resuscitated patients, respectively. The faster EMS systems initiated
      resuscitation more frequently and also had a higher discharge rate with good
      neurological outcome in proportion to the population of the catchment area (7.7
      versus 5.6 persons per 100 000 population per year, odds ratio [OR] 0.72, 95%
      confidence interval [0.66; 0.79], p<0.001). CONCLUSION: Rapid ambulance response
      is associated with a higher rate of survival from OHCA with good neurological
      outcome. The response time, independently of whether bystander resuscitation
      measures are provided, ha^ a significant independent effect on the survival rate.
      In drawing conclusions from these findings, one should bear in mind that this was
      a retrospective registry study, with the corresponding limitations.

PMID- 30189975
TI  - The Peppered Brain Stem.

PMID- 30189974
TI  - Depressive Symptoms in Adolescents.
AB  - BACKGROUND: In this study, we determined the current prevalence of depressive
      symptoms in adolescents in Germany. METHODS: A sample of 1001 adolescents aged 12
      to 17 that was representative for Germany was surveyed in August and September
      2017 through telephone interviews about depressive symptoms in the two weeks
      leading up to the interview and about the subjects' psychosocial features. The
      instrument that was used, called DesTeen, includes questions about depressed
      mood, loss of interest, loss of energy, feelings of worthlessness, guilt
      feelings, and cognitive symptoms. RESULTS: Prevalences could be estimated and
      associated factors could be determined in a subset comprising 988 of the original
      1001 subjects (mean age 14.58 years, 48.4% female). The estimated point
      prevalence of depressive symptoms (summated DesTeen score >= 14) in adolescents
      aged 12 to 17 was 8.2% (95% confidence interval [6.5; 9.9]). Girls (11.6% [95% CI
      8.8; 14.4]) were more commonly affected than boys (5.0% [95% CI 3.1; 6.9]), and
      this difference was statistically significant (p<0.001). Depressive symptoms were
      more common with female sex, older age, poorer scholastic performance, lower
      interpersonal trust, more negative body image, more problematic use of social
      media or computer games, and lower family functioning. A multivariable regression
      model explained approximately one-third of the variation among groups
      (Nagelkerke's R2 = 0.35). CONCLUSION: A substantial percentage of German
      adolescents suffers from depres - sive symptoms. This study was the first to show
      certain associations, such as that between depressive symptoms in adolescence and
      the problematic use of social media in German youth.

PMID- 30189976
TI  - False Comparison, and Interdisciplinary Approach Is Lacking.

PMID- 30189977
TI  - In Reply.

PMID- 30189979
TI  - An Introduction to Orofacial Pain.
AB  - The assessment, diagnosis, and management of orofacial pain (OFP) disorders is
      often a complex, multifactorial, and multidisciplinary process. Nociception leads
      to the perception of pain, causing the personal experience of suffering, which
      results in pain behavior. Many patients present with various comorbidities that
      may influence these conditions in a multitude of ways. The clinical presentation
      of OFP often includes biological, psychological, social, behavioral, and belief
      system components.

PMID- 30189978
TI  - Arterial Hypertension.
AB  - BACKGROUND: Essential arterial hypertension is one of the main treatable
      cardiovascular risk factors. In Germany, approximately 13% of women and 18% of
      men have uncontrolled high blood pressure (>= 140/90 mmHg). METHODS: This review
      is based on pertinent publications retrieved by a selective literature search in
      PubMed. RESULTS: Arterial hypertension is diagnosed when repeated measurements in
      a doctor's office yield values of 140/90 mmHg or higher. The diagnosis should be
      confirmed by 24-hour ambulatory blood pressure monitoring or by home measurement.
      Further risk factors and end-organ damage should be considered as well. According
      to the current European guidelines, the target blood pressure for all patients,
      including those with diabetes mellitus or renal failure, is <140/90 mmHg. If the
      treatment is well tolerated, further lowering of blood pressure, with a defined
      lower limit, is recommended for most patients. The main non-pharmacological
      measures against high blood pressure are reduction of salt in the diet, avoidance
      of excessive alcohol consumption, smoking cessation, a balanced diet, physical
      exercise, and weight loss. The first-line drugs for arterial hypertension include
      long-acting dihydropyridine calcium channel blockers, angiotensin-converting
      enzyme inhibitors or angiotensin-receptor blockers, and thiazide-like diuretics.
      Mineralocorticoid-receptor blockers are effective in patients whose blood
      pressure cannot be brought into acceptable range with first-line drugs.
      CONCLUSION: In most patients with essential hypertension, the blood pressure can
      be well controlled and the cardiovascular risk reduced through a combination of
      lifestyle interventions and first-line antihypertensive drugs.

PMID- 30189980
TI  - Assessment of the Orofacial Pain Patient.
AB  - The diagnostic process of pain in the oral, facial, and head region is often
      perceived as more difficult due the numerous, extensively innervated structures
      located in this area. To successfully manage the patient with these pain
      presentations, it is critical for the clinician to spend ample time procuring a
      good medical and dental history. A systematic approach to the physical
      examination will ensure that sufficient data are acquired without overlooking
      potentially important contributing factors. The use of adjunctive laboratory
      tests and imaging studies should be based on the findings in the history and
      examination.

PMID- 30189981
TI  - Imaging in Orofacial Pain.
AB  - Imaging usefulness in the diagnosis of orofacial pain includes all modalities
      that cover the soft tissue and bony structures in the region of the head and
      neck. Imaging techniques may include 2-dimensional and/or 3-dimensional imaging
      modalities. Both dentists and physicians should be aware of orofacial pain
      associated with a variety of sources and select the appropriate imaging technique
      based on the patient's medical and dental history and the clinical examination.
      The goal of imaging is to provide the clinician with information that will
      confirm or deny findings of the clinical examination and allow for the selection
      of an appropriate treatment.

PMID- 30189982
TI  - Musculoskeletal Disorders.
AB  - Temporomandibular disorder (TMD), a type of musculoskeletal pain, is a main cause
      of pain in the orofacial region. It involves the masticatory muscles,
      temporomandibular joints (TMJs), and associated structures. The most common signs
      and symptoms are pain, limited range of motion, and TMJ sounds. TMD is a highly
      prevalent condition with a multifactorial etiology. Management aims to reduce
      pain and to improve function using a combination of therapeutic options.
      Noninvasive techniques are the first option and should be indicated considering
      the needs of each individual, the clinical features, and the mechanisms involved.

PMID- 30189983
TI  - Neuropathic Orofacial Pain.
AB  - Neuropathic pain of the orofacial region can cause much distress in individuals
      presenting with this condition. It may be easily mistaken for dental pain, and
      hence many individuals may undergo unnecessary dental work. Knowledge of the
      types of neuropathic orofacial pain may assist in timely diagnosis and
      improvement of a patient's quality of life.

PMID- 30189984
TI  - Burning Mouth Syndrome.
AB  - Burning mouth syndrome (BMS) is a chronic disorder for which a definitive
      etiopathology is not known. The BMS patient often experiences a continuous
      burning pain in the mouth without any clinical signs. This confusing condition
      can create frustration for both patient and practitioner. Ultimately, it is
      important for the practitioner who treats head and face pain to become
      knowledgeable in the recognition of the many complexities and various
      presentations associated with BMS. In doing so, the practitioner can be better
      prepared to help patients cope with this confounding disorder and gain a better
      quality of life.

PMID- 30189985
TI  - Painful Oral Lesions.
AB  - Painful oral vesiculoerosive diseases (OVD) include lichen planus, pemphigus
      vulgaris, mucous membrane pemphigoid, erythema multiforme, and recurrent aphthous
      stomatitis. OVD lesions have an immunopathic cause. Treatment is aimed at
      reducing the immunologic and the following inflammatory response. The mainstay of
      OVD management is topical or systemic corticosteroids to include topical
      triamcinolone, fluocinonide, and clobetasol, whereas systemic medications used in
      practice can include dexamethasone, prednisone, and prednisolone. Oral herpetic
      lesions can be primary or recurrent. If management is desired, they can be
      treated by topical or systemic antiviral drugs. Topical antiviral creams include
      prescription acyclovir, penciclovir and over-the-counter docosanol.

PMID- 30189986
TI  - Primary Headaches.
AB  - The primary headaches are composed of multiple entities that cause episodic and
      chronic head pain in the absence of an underlying pathologic process, disease, or
      traumatic injury. The most common of these are migraine, tension-type headache,
      and the trigeminal autonomic cephalalgias. This article reviews the clinical
      presentation, pathophysiology, and treatment of each to help in differential
      diagnosis. These headache types share many common signs and symptoms, thus a
      clear understanding of each helps prevent a delay in diagnosis and inappropriate
      or ineffective treatment. Many of these patients seek dental care because
      orofacial pain is a common presenting symptom.

PMID- 30189987
TI  - Sleep and Orofacial Pain.
AB  - Sleep and pain share a bidirectional relationship. Therefore, it is important for
      practitioners managing patients experiencing either sleep and/or pain issues to
      recognize and understand this complex association from a neurobiological
      perspective involving neuroanatomic and neurochemical processes. Accounting for
      the influence of pain on the various aspects of sleep and understanding its
      impact on various orofacial pain disorders assists in developing a prudent
      management approach. Screening for sleep disorders benefits practitioners in
      identifying these individuals. Instituting evidence-based multidisciplinary
      management strategies using both behavioral and pharmacologic strategies enhances
      the delivery of appropriate care.

PMID- 30189988
TI  - Sleep Bruxism and Pain.
AB  - Bruxism is an oral behavior that may lead to repetitive jaw-muscle activity
      characterized by clenching or grinding of the teeth and/or by bracing or
      thrusting of the mandible with 2 distinct circadian manifestations: sleep bruxism
      or awake bruxism. They share common risk factors and lead to similar consequences
      for the masticatory system but may have different etiology and pathophysiology.
      This oral behavior has been associated with tooth wear, masticatory muscle
      tenderness, headaches, and painful temporomandibular disorders. Available
      scientific evidence does not support the view that bruxism is a direct cause of
      pain, which should be taken into account when treating/managing patients.

PMID- 30189989
TI  - Sex, Gender, and Orofacial Pain.
AB  - This review examines gender prevalence in orofacial pain to elucidate underlying
      factors that can explain such differences. This review highlights how gender
      affects (1) the association of hormonal factors and pain modulation; (2) the
      genetic aspects influencing pain sensitivity and pain perception; (3) the role of
      resting blood pressure and pain threshold; and (4) the impact of sociocultural,
      environmental, and psychological factors on pain.

PMID- 30189990
TI  - Mind-Body Considerations in Orofacial Pain.
AB  - This article summarizes the cognitive, behavioral, and emotional factors that
      contribute to the onset and maintenance of orofacial pain. These orofacial pain
      conditions illustrate the dynamic interplay of the mind and body and the
      importance of multimodal treatment approaches addressing simultaneously the
      cognitive, behavioral, and physiologic dimensions of facial pain. Cognitive and
      behavioral treatments of temporomandibular disorders based on the outcomes of
      randomized controlled trials are also discussed with an emphasis on using a
      biopsychosocial perspective when working with the persons who have
      temporomandibular disorders.

PMID- 30189991
TI  - Orofacial Pain: Where We Are and Where We Are Going.

PMID- 30189993
TI  - [Metacholine challenge: The D-dimer of asthma diagnosis?]

PMID- 30189995
TI  - What to Do When Blood Pressure Is Between 130/80 and 139/89 mm Hg?

PMID- 30189994
TI  - 2017 ACC/AHA Blood Pressure Treatment Guideline Recommendations and
      Cardiovascular Risk.
AB  - BACKGROUND: The 2017 American College of Cardiology/American Heart Association
      (ACC/AHA) blood pressure (BP) guideline provides updated recommendations for
      antihypertensive medication initiation and intensification. OBJECTIVES: Determine
      the risk for cardiovascular disease (CVD) events among adults recommended and not
      recommended antihypertensive medication initiation or intensification by the 2017
      ACC/AHA BP guideline. METHODS: The authors analyzed data for black and white
      REGARDS (REasons for Geographic And Racial Differences in Stroke) study
      participants (age >=45 years). Systolic BP (SBP) and diastolic BP (DBP) were
      measured twice at baseline (2003 to 2007) and averaged. Participants not taking
      (n = 14,039) and taking (n = 15,179) antihypertensive medication were categorized
      according to their recommendations for antihypertensive medication initiation and
      intensification by the 2017 ACC/AHA guideline. Overall, 4,094 CVD events (stroke,
      coronary heart disease, and heart failure) occurred by December 31, 2014.
      RESULTS: Among participants not taking antihypertensive medication, 34.4% were
      recommended pharmacological antihypertensive treatment initiation. The CVD event
      rate per 1,000 person-years among participants recommended antihypertensive
      medication initiation with SBP/DBP >=140/90 mm Hg was 22.7 (95% confidence
      interval [CI]: 20.3 to 25.0). Among participants with SBP/DBP 130 to 139/80 to 89
      mm Hg, the CVD event rate was 20.5 (95% CI: 18.5 to 22.6) and 3.4 (95% CI: 2.4 to
      4.4) for those recommended and not recommended antihypertensive medication
      initiation, respectively. Among participants taking antihypertensive medication,
      62.8% were recommended treatment intensification. The CVD event rate per 1,000
      person-years among participants recommended treatment intensification was 33.6
      (95% CI: 31.5 to 35.6) and 22.4 (95% CI: 20.8 to 23.9) for those with SBP/DBP
      >=140/90 mm Hg and 130 to 139/80 to 89 mm Hg, respectively. CONCLUSIONS:
      Implementing the 2017 ACC/AHA guideline would direct antihypertensive medication
      initiation and intensification to adults with high CVD risk.

PMID- 30189997
TI  - Epidemiological Versus Trial Evidence for Hypertension Treatment: Adding a Piece
      to the Puzzle.

PMID- 30189996
TI  - Long-Term Cardiovascular Risk Associated With Stage 1 Hypertension Defined by the
      2017 ACC/AHA Hypertension Guideline.
AB  - BACKGROUND: Systolic/diastolic blood pressure (BP) of 130 to 139/80 to 89 mm Hg
      has been recently defined as stage 1 hypertension by the 2017 American College of
      Cardiology/American Heart Association hypertension guideline. To what extent this
      BP stratum affects cardiovascular risk needs to be quantified in considering its
      adoption in China. OBJECTIVES: The purpose of this study was to assess the
      relative risk and population-attributable risk of cardiovascular disease (CVD)
      associated with stage 1 hypertension and age-specific differences. METHODS: In
      total, 21,441 participants age >=35 years and free of CVD at baseline were
      followed for up to 20 years in the Chinese Multi-provincial Cohort Study. The
      adjusted hazard ratio (HR) and population-attributable risk for CVD associated
      with stage 1 hypertension were calculated. RESULTS: Participants with stage 1
      hypertension accounted for 25.8% of the cohort. Among participants age 35 to 59
      years, the HR comparing stage 1 hypertension to BP <120/<80 mm Hg for CVD
      incidence was 1.78 (95% confidence interval [CI]: 1.50 to 2.11), coronary heart
      disease incidence was HR: 1.77 (95% CI: 1.33 to 2.36), stroke incidence was HR:
      1.79 (95% CI: 1.45 to 2.22), and CVD mortality was HR: 2.50 (95% CI: 1.66 to
      3.77). The proportions of cardiovascular deaths and events attributable to stage
      1 hypertension were 26.5% and 13.4% among participants age 35 to 59 years,
      respectively. Among participants age >=60 years, however, stage 1 hypertension
      was not related to increased risk compared with BP <120/<80 mm Hg, and population
      attributable risk associated with this stratum was not found. Over a 15-year
      period, 65.0% of participants age 35 to 59 years with stage 1 hypertension
      experienced an increase in BP to 140/90 mm Hg or higher, and they had a 3.01-fold
      increased cardiovascular risk compared with those who maintained BP <130/<80 mm
      Hg. CONCLUSIONS: The effect of 2017 American College of Cardiology/American Heart
      Association stage 1 hypertension on cardiovascular risk is evidenced in young and
      middle-aged Chinese adults, but not in those age >=60 years.

PMID- 30189998
TI  - Generalizing Intensive Blood Pressure Treatment to Adults With Diabetes Mellitus.
AB  - BACKGROUND: Controversy over blood pressure (BP) treatment targets for
      individuals with diabetes is in part due to conflicting perspectives about
      generalizability of available trial data. OBJECTIVE: The authors sought to
      estimate how results from the largest clinical trial of intensive BP treatment
      among adults with diabetes would generalize to the U.S. POPULATION:  METHODS: The
      authors used transportability methods to reweight individual patient data from
      the ACCORD (Action to Control Cardiovascular Risk in Diabetes) BP trial (N =
      4,507) of intensive (goal systolic BP <120 mm Hg) versus standard (goal systolic
      BP <140 mm Hg) treatment to better represent the demographic and clinical risk
      factors of the U.S. population of adults with diabetes (data from NHANES
      [National Health and Nutrition Examination Survey] 2005 to 2014, n = 1,943). The
      primary outcome was the first occurrence of nonfatal myocardial infarction,
      nonfatal stroke, or cardiovascular death. Analysis used weighted Cox proportional
      hazards regression models with robust standard errors. RESULTS: The ACCORD BP
      sample had less racial/ethnic diversity and more elevated cardiovascular risk
      factors than the NHANES participants. Weighted results significantly favored
      intensive BP treatment, unlike unweighted results (hazard ratio for primary
      outcome in intensive versus standard treatment in weighted analyses: 0.67, 95%
      confidence interval: 0.49 to 0.91; in unweighted analyses: hazard ratio: 0.88,
      95% confidence interval: 0.73 to 1.07). Over 5 years, the weighted results
      estimate a number needed to treat of 34, and number needed to harm of 55.
      CONCLUSIONS: After reweighting to better reflect the U.S. adult population with
      diabetes, intensive BP therapy was associated with significantly lower risk for
      cardiovascular events. However, data were limited among racial/ethnic minorities
      and those with lower cardiovascular risk.

PMID- 30189999
TI  - Presence of Diabetes Does Not Mandate Lower Blood Pressure to Reduce
      Cardiovascular Events.

PMID- 30190000
TI  - Low Diastolic Blood Pressure Is Associated With Angina in Patients With Chronic
      Coronary Artery Disease.
AB  - BACKGROUND: In patients with coronary artery disease (CAD), low diastolic blood
      pressure (DBP) is associated with increased risk of myocardial infarction, but
      its association with angina is unknown. OBJECTIVES: The goal of this study was to
      examine the association of low DBP and angina in patients with CAD. METHODS: The
      study assessed the frequency of angina (measured by using the Seattle Angina
      Questionnaire-Angina Frequency score) according to DBP in patients with known CAD
      from 25 U.S. cardiology clinics. Hierarchical logistic regression was used to
      test the association between DBP and angina, with a spline term for DBP to assess
      nonlinearity. RESULTS: Among 1,259 outpatients with CAD, 411 (33%) reported
      angina in the prior month, with higher rates in the lowest DBP quartile (40 to 64
      mm Hg: 37%). In the unadjusted model, DBP was associated with angina with a J
      shaped relationship (p = 0.017, p for nonlinearity = 0.027), with a progressive
      increase in odds of angina as DBP decreased below ~70 to 80 mm Hg. This
      association remained significant after sequential adjustment for demographic
      characteristics (p = 0.002), comorbidities (p = 0.002), heart rate (p = 0.002),
      systolic blood pressure (p = 0.046), and antihypertensive antianginal medications
      (p = 0.045). CONCLUSIONS: In patients with chronic CAD, there seemed to be an
      association between lower DBP and increased odds of angina. If validated, these
      findings suggest that clinicians should consider less aggressive blood pressure
      control in patients with CAD and angina.

PMID- 30190002
TI  - Hypertension Guidelines: The Threads That Bind Them.

PMID- 30190001
TI  - Ideal Blood Pressure in Patients With Atrial Fibrillation.
AB  - BACKGROUND: The 2017 American College of Cardiology/American Heart Association
      (ACC/AHA) Guideline for High Blood Pressure in Adults redefined hypertension as
      systolic blood pressure (BP) >=130 mm Hg or diastolic BP >=80 mm Hg. The optimal
      BP for patients with atrial fibrillation (AF) is uncertain. OBJECTIVES: The goal
      of this study was to investigate the impacts of the 2017 ACC/AHA guideline and to
      determine the ideal BP threshold for the management of high BP in patients with
      AF. METHODS: This study analyzed data for 298,374 Korean adults with oral
      anticoagulant-naive, nonvalvular AF obtained from the National Health Insurance
      Service database from 2005 to 2015. RESULTS: According to the Seventh Report of
      the Joint National Committee on Prevention, Detection, Evaluation and Treatment
      of High Blood Pressure guideline, 62.2% of the individuals in our sample had
      hypertension. After applying the 2017 ACC/AHA guideline, 79.4% had hypertension,
      including 17.2% with newly redefined hypertension (130 to 139/80 to 89 mm Hg).
      Those with newly redefined hypertension had greater risks of major cardiovascular
      events (hazard ratio: 1.07; 95% confidence interval: 1.04 to 1.10; p < 0.001),
      ischemic stroke, intracranial hemorrhage, and heart failure admission, compared
      with nonhypertensive patients (<130/80 mm Hg). Among patients with AF undergoing
      hypertension treatment, patients with BP >=130/80 mm Hg or <120/80 mm Hg were at
      significantly higher risks of major cardiovascular events than patients with BP
      of 120 to 129/<80 mm Hg. CONCLUSIONS: Patients with AF and newly redefined
      hypertension according to the 2017 ACC/AHA guideline were at higher risk of major
      cardiovascular events, suggesting that the new BP threshold is beneficial for
      timely diagnosis and intervention. BP of 120 to 129/<80 mm Hg was the optimal BP
      treatment target for patients with AF undergoing hypertension treatment.

PMID- 30190004
TI  - Hypertensive Disorders of Pregnancy and CVD Prediction: Accounting for Risk
      Accrual During the Reproductive Years.

PMID- 30190003
TI  - Hypertensive Disorders of Pregnancy and 10-Year Cardiovascular Risk Prediction.
AB  - BACKGROUND: Hypertensive disorders of pregnancy (HDP) affect 10% to 15% of women
      and are associated with a 2-fold increased risk of cardiovascular disease (CVD).
      OBJECTIVES: This study sought to determine whether inclusion of HDP in an
      established CVD risk score improves prediction of CVD events in women. METHODS:
      The analysis comprised 106,230 <=10-year observations contributed by 67,406
      women, age >=40 years, free of prior CVD, with data available on model covariates
      in the Nurses' Health Study II. Participants were followed up for confirmed
      myocardial infarction, fatal coronary heart disease, or stroke from 1989 to 2013.
      We fit an established CVD risk prediction model (Model A: age, total cholesterol
      and high-density lipoprotein cholesterol, systolic blood pressure,
      antihypertensive medication use, current smoking, diabetes mellitus) and compared
      it to the same model plus HDP and parity (Model B); Cox proportional hazards
      models were used to obtain predicted probabilities for 10-year CVD risk. RESULTS:
      HDP and parity were associated with 10-year CVD risk independent of established
      CVD risk factors, overall and at ages 40 to 49 years. However, inclusion of HDP
      and parity in the risk prediction model did not improve discrimination (Model A:
      C-index = 0.691; Model B: C-index = 0.693; p value for difference = 0.31) or risk
      reclassification (net reclassification improvement = 0.4%; 95% confidence
      interval: -0.2 to 1.0%; p = 0.26). CONCLUSIONS: In this first test of the
      clinical utility of HDP and parity in CVD risk prediction, additional inclusion
      of HDP and parity in an established risk score did not improve discrimination or
      reclassification in this low-risk population; this might be because of the known
      associations between HDP and established CVD risk factors in the reference model.

PMID- 30190006
TI  - Epigenetics: Is the Mode of Conception a Marker for Future Cardiovascular Risk?

PMID- 30190005
TI  - Association of Assisted Reproductive Technologies With Arterial Hypertension
      During Adolescence.
AB  - BACKGROUND: Assisted reproductive technologies (ART) have been shown to induce
      premature vascular aging in apparently healthy children. In mice, ART-induced
      premature vascular aging evolves into arterial hypertension. Given the young age
      of the human ART group, long-term sequelae of ART-induced alterations of the
      cardiovascular phenotype are unknown. OBJECTIVES: This study hypothesized that
      vascular alterations persist in adolescents and young adults conceived by ART and
      that arterial hypertension possibly represents the first detectable clinically
      relevant endpoint in this group. METHODS: Five years after the initial
      assessment, the study investigators reassessed vascular function and performed 24
      h ambulatory blood pressure (BP) monitoring (ABPM) in 54 young, apparently
      healthy participants conceived through ART and 43 age- and sex-matched controls.
      RESULTS: Premature vascular aging persisted in ART-conceived subjects, as
      evidenced by a roughly 25% impairment of flow-mediated dilation of the brachial
      artery (p < 0.001) and increased pulse-wave velocity and carotid intima-media
      thickness. Most importantly, ABPM values (systolic BP, 119.8 +/- 9.1 mm Hg vs.
      115.7 +/- 7.0 mm Hg, p = 0.03; diastolic BP, 71.4 +/- 6.1 mm Hg vs. 69.1 +/- 4.2
      mm Hg, p = 0.02 ART vs. control) and BP variability were markedly higher in ART
      conceived subjects than in control subjects. Eight of the 52 ART participants,
      but only 1 of the 43 control participants (p = 0.041 ART vs. controls) fulfilled
      ABPM criteria of arterial hypertension (>130/80 mm Hg and/or >95th percentile).
      CONCLUSIONS: ART-induced premature vascular aging persists in apparently healthy
      adolescents and young adults without any other detectable classical
      cardiovascular risk factors and progresses to arterial hypertension. (Vascular
      Dysfunction in Offspring of Assisted Reproduction Technologies; NCT00837642.).

PMID- 30190007
TI  - Prevention and Control of Hypertension: JACC Health Promotion Series.
AB  - Hypertension, the leading risk factor for cardiovascular disease, originates from
      combined genetic, environmental, and social determinants. Environmental factors
      include overweight/obesity, unhealthy diet, excessive dietary sodium, inadequate
      dietary potassium, insufficient physical activity, and consumption of alcohol.
      Prevention and control of hypertension can be achieved through targeted and/or
      population-based strategies. For control of hypertension, the targeted strategy
      involves interventions to increase awareness, treatment, and control in
      individuals. Corresponding population-based strategies involve interventions
      designed to achieve a small reduction in blood pressure (BP) in the entire
      population. Having a usual source of care, optimizing adherence, and minimizing
      therapeutic inertia are associated with higher rates of BP control. The Chronic
      Care Model, a collaborative partnership among the patient, provider, and health
      system, incorporates a multilevel approach for control of hypertension.
      Optimizing the prevention, recognition, and care of hypertension requires a
      paradigm shift to team-based care and the use of strategies known to control BP.

PMID- 30190008
TI  - Orthostatic Hypotension: JACC State-of-the-Art Review.
AB  - Neurogenic orthostatic hypotension is a highly prevalent and disabling feature of
      autonomic failure due to both peripheral and central neurodegenerative diseases.
      Community-based epidemiological studies have demonstrated a high morbidity and
      mortality associated with neurogenic orthostatic hypotension. It is due to
      impairment of baroreflex-mediated vasoconstriction of the skeletal muscle and
      splanchnic circulation and is caused by damage or dysfunction at central and/or
      peripheral sites in the baroreflex efferent pathway. Nonpharmacological and
      pharmacological interventions may be implemented to ameliorate the symptoms of
      orthostatic intolerance and improve quality of life. Many patients will be
      adequately treated by education, counseling, removal of hypotensive medications,
      and other nonpharmacological interventions, whereas more severely afflicted
      patients require pharmacological interventions. The first stage of
      pharmacological treatment involves repletion of central blood volume. If
      unsuccessful, this should be followed by treatment with sympathomimetic agents.

PMID- 30190009
TI  - The American College of Cardiology: Strategically Aligning for the Next 5 Years.

PMID- 30190010
TI  - The Blood Pressure Landscape: Schism Among Guidelines, Confusion Among
      Physicians, and Anxiety Among Patients.

PMID- 30190011
TI  - Intensive Blood Pressure Control and Body Size.

PMID- 30190012
TI  - Hypertensive Disorders During Pregnancy and Offspring Retinal Microvasculature
      During Adolescence.

PMID- 30190013
TI  - Membrane trafficking and cytoskeletal dynamics in neuronal function.

PMID- 30190014
TI  - Genomic Landscape of Waldenstrom Macroglobulinemia.
AB  - Next-generation sequencing has revealed recurring somatic mutations in
      Waldenstrom macroglobulinemia (WM). Common mutations include MYD88 (95%-97%), as
      well as CXCR4 (30%-40%), ARID1A (17%), and CD79B (8%-15%), which are typically
      found in MYD88-mutated patients. The genomic findings provide important insights
      into the pathogenesis, prognostication, and treatment outcome in WM. We discuss
      the genomic landscape of WM, and the impact of underlying genomics on disease
      presentation, transcriptional changes, treatment outcome, and overall survival
      impact.

PMID- 30190015
TI  - Working Toward a Genomic Prognostic Classification of Waldenstrom
      Macroglobulinemia: C-X-C Chemokine Receptor Type 4 Mutation and Beyond.
AB  - Waldenstrom macroglobulinemia is a rare indolent B-cell lymphoma. Whole-exome
      sequencing studies have improved our knowledge of the Waldenstrom
      macroglobulinemia mutational landscape. The MYD88 L265P mutation is present in
      nearly 90% of patients with Waldenstrom macroglobulinemia. CXCR4 mutations are
      identified in approximately 30% of MYD88L265P cases and have been associated with
      ibrutinib resistance in clinical trials. Mutations in CD79B, ARID1a, or TP53 were
      described at lower frequency. Deciphering the earliest initiating lesions and
      identifying the molecular alterations leading to disease progression currently
      represent important goals in the future to identify the most relevant targets for
      precision therapy in Waldenstrom macroglobulinemia.

PMID- 30190016
TI  - Flow Cytometry.
AB  - Multiparameter flow cytometry (MFC) is valuable in the diagnosis and monitoring
      of most hematological malignancies. Although the assessment of cellular
      infiltrates in Waldenstrom macroglobulinemia (WM) relies on morphology and
      immunohistochemistry grounds, there is evidence pointing to the clinical
      significance of MFC in this disease. Herein, the authors review immunophenotypic
      patterns of B-cell development, the antigen profile of the WM clone and its
      normal B-cell counterpart, the clinical applicability of MFC in the differential
      diagnosis of immunoglobulin M-secreting lymphoproliferative disorders and
      monoclonal gammopathies, and its potential role in detecting minimal residual
      disease and monitoring treatment efficacy in WM.

PMID- 30190017
TI  - The Bone Marrow Microenvironment in Waldenstrom Macroglobulinemia.
AB  - Waldenstrom macroglobulinemia (WM) is an indolent B-cell lymphoma defined
      predominantly by infiltration of lymphoplasmacytic cells into the bone marrow
      (BM) and increased production of monoclonal immunoglobulin M (IgM) by
      lymphoplasmacytic cells, and the secretion of IgM is enhanced by cytokines in the
      bone marrow microenvironment. This article highlights the available data
      regarding the interaction of WM cells with both the cellular and noncellular
      compartments of the BM microenvironment and discusses how the BM promotes
      malignant cell growth and increases IgM production in this disease.

PMID- 30190019
TI  - Initial Evaluation of the Patient with Waldenstrom Macroglobulinemia.
AB  - The initial evaluation of the patient with Waldenstrom macroglobulinemia can be
      challenging. Not only is it a rare disease, but the clinical features can vary
      greatly from patient to patient. In this article, we aim at providing concise and
      practical recommendations for the initial evaluation of patients with Waldenstrom
      macroglobulinemia, specifically regarding history taking, physical examination,
      laboratory testing, bone marrow aspiration, and biopsy evaluation and imaging
      studies. We then review the most common special clinical situations seen in
      patients with Waldenstrom macroglobulinemia, especially anemia, hyperviscosity,
      cryoglobulinemia, peripheral neuropathy, extramedullary disease, Bing-Neel
      syndrome, and amyloidosis.

PMID- 30190018
TI  - Familial Waldenstrom Macroglobulinemia: Families Informing Populations.
AB  - Familial clustering of Waldenstrom macroglobulinemia (WM) has been observed for
      nearly 6 decades. Family studies have provided seminal observations in
      delineating the phenotypic spectrum of WM susceptibility and confirming the
      importance of immunoglobulin M (IgM) monoclonal gammopathy of undetermined
      significance (IgM MGUS) as a precursor condition for WM, providing the rationale
      for large population-based epidemiologic studies of IgM MGUS and WM, and
      providing both the basis and the material for ongoing genetic studies aimed at
      identifying WM predisposition genes. Together, these investigations may help
      elucidate the host factors underlying WM development.

PMID- 30190020
TI  - Alkylating Agents in the Treatment of Waldenstrom Macroglobulinemia.
AB  - The introduction of ibrutinib has grossly changed the treatment landscape in
      patients with Waldenstrom's Macroglobulinemia. Nevertheless, chemotherapy in
      combination with rituximab is still a cornerstone treatment. Among
      chemotherapeutics, alkylating agents are most frequently used. Rituximab,
      cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is a highly
      effective but potentially neurotoxic regimen. Dexamethasone, rituximab, and
      cyclophosphamide (DRC) induces long responses and has a favorable toxicity
      profile. Bendamustine was shown to be among the most potent chemotherapeutics in
      combination with rituximab. Future studies must define the role of alkylating
      agents, which compete with highly effective chemotherapy-free targeted therapies.

PMID- 30190021
TI  - Proteasome Inhibitors in Waldenstrom Macroglobulinemia.
AB  - Waldenstrom macroglobulinemia (WM) remains an incurable B-cell
      lymphoproliferative disorder, yet therapy is only considered for patients with
      symptomatic disease. Primary therapy options for WM include combinations based on
      anti-CD20 monoclonal antibodies, mainly rituximab. However, proteasome inhibitors
      have become an important part of WM therapy both as primary therapy and as
      salvage option. Bortezomib is the proteasome inhibitor most studied and with
      extensive clinical experience, but new proteasome inhibitors (carfilzomib,
      ixazomib, oprozomib), with different toxicity profiles, routes of administration,
      and probably with preserved or improved activity, have become available and may
      also find their way into WM therapy.

PMID- 30190022
TI  - Monoclonal Antibodies for Waldenstrom Macroglobulinemia.
AB  - For the last 2 decades, anti-CD20 monoclonal antibodies have revolutionized the
      treatment of patients with B-cell lymphomas. These agents have shown efficacy
      when used as single agents and also have improved response and survival rates
      when added to chemotherapy. Monoclonal antibodies are safe and effective as well
      in patients with Waldenstrom macroglobulinemia (WM). The purpose of this article
      is to review the mechanism of action of monoclonal antibodies and to discuss
      current clinical data supporting their use in patients with WM. This review
      focuses on retrospective and prospective studies and clinical trials on anti-CD20
      antibodies, anti-CD38 antibody, and anti-CXCR4 antibody.

PMID- 30190023
TI  - First-Generation and Second-Generation Bruton Tyrosine Kinase Inhibitors in
      Waldenstrom Macroglobulinemia.
AB  - Waldenstrom macroglobulinemia (WM) is an indolent B-cell lymphoma that is heavily
      dependent on Bruton tyrosine kinase (BTK) hyperactivation. Ibrutinib is a first
      generation BTK inhibitor that has shown high activity and durable responses in
      patients with relapsed/refractory WM. Newer and more selective BTK inhibitors are
      currently being tested in several clinical trials and are expected to address the
      toxicity and the acquired resistance observed in patients receiving ibrutinib.
      Updates on ibrutinib and second-generation BTK inhibitors are summarized in this
      review.

PMID- 30190024
TI  - High-Dose Therapy and Hematopoietic Stem Cell Transplantation in Waldenstrom
      Macroglobulinemia.
AB  - Waldenstrom macroglobulinemia (WM) is an indolent low-grade non-Hodgkin lymphoma
      characterized by bone marrow infiltration by lymphoplasmacytic cells and
      associated clonal IgM paraproteinemia. Recent insights into the biology and
      genomic characteristics of WM have provided a further platform for more targeted
      therapies. Despite the high response rates and better depth and duration of
      responses, the disease remains incurable. This review focuses on use of the high
      dose therapy with either autologous or allogeneic hematopoietic stem cell
      transplantation.

PMID- 30190025
TI  - Novel Approaches in Waldenstrom Macroglobulinemia.
AB  - Recent advances in the understanding of Waldenstrom macroglobulinemia (WM)
      biology have paved the way for development of a plethora of novel therapeutic
      strategies. The success of ibrutinib in WM has shifted treatment paradigms away
      from conventional chemoimmunotherapy approaches. Recognition of high-risk genomic
      subgroups as well as mechanisms of acquired resistance to ibrutinib have led to
      targeting of additional pathways. In this article, the authors review ongoing and
      emerging trials of novel therapies in WM that target the B-cell receptor pathway
      beyond ibrutinib, toll-like receptor pathway, chemokine signaling, apoptotic
      pathway, chromatin remodeling, protein transport, the immune microenvironment,
      and CD19-directed immunotherapy.

PMID- 30190026
TI  - Waldenstrom Macroglobulinemia: Lessons Learned from Basic and Clinical Research.

PMID- 30190027
TI  - How Active Is Active Surveillance in Asymptomatic Patients With Primary Mitral
      Regurgitation?

PMID- 30190028
TI  - Noninvasive Tissue Characterization of Post-Infarction Myocardium.

PMID- 30190029
TI  - Risk Stratification in Nonischemic Dilated Cardiomyopathy in the Era of
      Personalized Medicine: Can Cardiac Magnetic Resonance With Late Gadolinium
      Imaging "Enhance" Our Strategy?

PMID- 30190031
TI  - When Can We Defer Testing for Patients With Stable Chest Pain?

PMID- 30190030
TI  - Comparison of International Guidelines for Assessment of Suspected Stable Angina:
      Insights From the PROMISE and SCOT-HEART.
AB  - OBJECTIVES: This study sought to compare the performance of major guidelines for
      the assessment of stable chest pain including risk-based (American College of
      Cardiology/American Heart Association and European Society of Cardiology) and
      symptom-focused (National Institute for Health and Care Excellence) strategies.
      BACKGROUND: Although noninvasive testing is not recommended in low-risk
      individuals with stable chest pain, guidelines recommend differing approaches to
      defining low-risk patients. METHODS: Patient-level data were obtained from the
      PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) and
      SCOT-HEART (Scottish Computed Tomography of the Heart) trials. Pre-test
      probability was determined and patients dichotomized into low-risk and
      intermediate-high-risk groups according to each guideline's definitions. The
      primary endpoint was obstructive coronary artery disease on coronary computed
      tomography angiography. Secondary endpoints were coronary revascularization at 90
      days and cardiovascular death or nonfatal myocardial infarction up to 3 years.
      RESULTS: In total, 13,773 patients were included of whom 6,160 had coronary
      computed tomography angiography. The proportions of patients identified as low
      risk by the American College of Cardiology/American Heart Association, European
      Society of Cardiology, and National Institute for Health and Care Excellence
      guidelines, respectively, were 2.5%, 2.5%, and 10.0% within PROMISE, and 14.0%,
      19.8%, and 38.4% within SCOT-HEART. All guidelines identified lower rates of
      obstructive coronary artery disease in low- versus intermediate-high-risk
      patients with a negative predictive value of >=0.90. Compared with low-risk
      groups, all intermediate-high-risk groups had greater risks of coronary
      revascularization (odds ratio [OR]: 2.2 to 24.1) and clinical outcomes (OR: 1.84
      to 5.8). CONCLUSIONS: Compared with risk-based guidelines, symptom-focused
      assessment identifies a larger group of low-risk chest pain patients potentially
      deriving limited benefit from noninvasive testing. (Scottish Computed Tomography
      of the Heart Trial [SCOT-HEART]; NCT01149590; Prospective Multicenter Imaging
      Study for Evaluation of Chest Pain [PROMISE]; NCT01174550).

PMID- 30190032
TI  - Diagnostic Differentiation Between Arrhythmogenic Cardiomyopathy and Athlete's
      Heart by Using Imaging.
AB  - Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an important cause of
      sudden cardiac death (SCD) in youth and athletes. In the last decade, several
      studies focused on right ventricular (RV) remodeling in athletes and revealed
      that features of the physiological adaptation of the right heart to training,
      such as RV dilation, may overlap with those of ARVC. Therefore, a careful
      multiparametric evaluation is required for differential diagnosis in order to
      avoid false diagnosis of ARVC or, in contrast, fail to identify the risk of
      causing SCD. This review summarizes physiological adaptation of the RV to
      exercise and describes features that could help distinguishing between athlete's
      heart and ARVC.

PMID- 30190033
TI  - Molecular Imaging of Myocardial Inflammation With Positron Emission Tomography
      Post-Ischemia: A Determinant of Subsequent Remodeling or Recovery.
AB  - Inflammation after myocardial ischemia influences ventricular remodeling and
      repair and has emerged as a therapeutic target. Conventional diagnostic
      measurements address systemic inflammation but cannot quantify local tissue
      changes. Molecular imaging facilitates noninvasive assessment of leukocyte
      infiltration into damaged myocardium. Preliminary experience with 18F-labeled
      fluorodeoxyglucose ([18F]FDG) demonstrates localized inflammatory cell signal
      within the infarct territory as an independent predictor of subsequent
      ventricular dysfunction. Novel targeted radiotracers may provide additional
      insight into the enrichment of specific leukocyte populations. Challenges to
      wider implementation of inflammation imaging after myocardial infarction include
      accurate and reproducible quantification, prognostic value, and capacity to
      monitor inflammation response to novel treatment. This review describes
      myocardial inflammation following ischemia as a molecular imaging target and
      evaluates established and emerging radiotracers for this application.
      Furthermore, the potential role of inflammation imaging to provide prognostic
      information, support novel drug and therapeutic research, and assess biological
      response to cardiac disease is discussed.

PMID- 30190035
TI  - The Authors Reply.

PMID- 30190034
TI  - Building Coronary Lesion-Specific Predictive Models Using the Proper Prognostic
      Parameters: A Look Into the Computational Hemodynamics of the Matter.

PMID- 30190036
TI  - Patient Selection Criteria for Diagnostic Imaging for Ischemic Heart Disease:
      Desperately in Need of Revision.

PMID- 30190037
TI  - EJVES: The Leading Journal in Vascular Surgery, and One of Many Highlights for
      the ESVS Annual Meeting in Valencia.

PMID- 30190038
TI  - New Technology Failures: Who to Blame or Time to be Cautious?

PMID- 30190039
TI  - Editor's Choice - Mid-term Migration and Device Failure Following Endovascular
      Aneurysm Sealing with the Nellix Stent Graft System - a Single Centre Experience.
AB  - OBJECTIVE: Endovascular aneurysm sealing (EVAS) with the Nellix stent graft
      system is a novel concept in the management of abdominal aortic aneurysm (AAA)
      that aims to reduce the prevalence of all endoleaks following endovascular
      repair. There are few data describing the longer-term durability of this
      approach. The aim was to report the longer-term outcomes following EVAS in a
      single centre. METHODS: This is a retrospective review of all patients that
      underwent Nellix at Cambridge University Hospitals Foundation Trust. Factors that
      are described as device failure include secondary sac rupture, graft
      explantation, further surgical procedures for Type 1 endoleak, or major migration
      of the stent grafts with pressurisation of the aortic sac. RESULTS: A total of
      161 patients have been treated with Nellix. The indications included primary AAA
      (n = 115), ruptured AAA (n = 4), salvage of other aortic grafts (n = 18), primary
      iliac aneurysm (n = 6), and chimney EVAS (ChEVAS) for pararenal AAA (n = 18). In
      total there have been 42 graft failures in patients treated with EVAS for primary
      AAA. The 4 year freedom from graft failure was 42% in patients treated for
      primary AAA. Failures mostly occurred more than 2 years post-Nellix implant.
      There were eight secondary sac ruptures (incidence 2.4 per 100 person years) and
      there have been 14 graft explants. CONCLUSIONS: Failure of aneurysm sealing
      following treatment with Nellix has been more common than anticipated and can
      cause aortic rupture. Post-operative surveillance of Nellix stent grafts is
      crucial to identify features of failure.

PMID- 30190040
TI  - Anxiety, depression and probability of live birth in a cohort of women with self
      reported infertility in the HUNT 2 Study and Medical Birth Registry of Norway.
AB  - OBJECTIVE: The 'psychogenic' hypothesis has a long history in the field of
      infertility. The present study investigated whether anxiety or depressive
      symptoms are associated with probability of subsequent live birth in a cohort of
      infertile women from the general population. METHODS: Using linked data from
      12,987 women in the North-Trondelag Health Study 1995-97 (HUNT 2) and the Medical
      Birth Registry of Norway (MBRN) a cohort of 467 women with self-reported
      infertility was followed prospectively in the MBRN for 11 years with regard to
      live birth. Anxiety and depressive symptoms were measured at baseline in HUNT 2
      by the Hospital Anxiety and Depression Scale (HADS), i.e. the Anxiety (HADS-A)
      and Depression (HADS-D) sub-scales. The relationship between anxiety or
      depressive symptoms and live birth in the MBRN was analysed using Cox
      proportional hazards regression analysis. RESULTS: Anxiety and depressive
      symptoms were not associated with live birth rates. For anxiety symptoms, the
      crude hazard ratios (HR) for live birth was 1.004 (95% confidence interval (CI) =
      0.96; 1.05); adjusted HR = 0.99 (95% CI = 0.94; 1.04), for depressive symptoms
      crude HR was 0.98 (95% CI = 0.92; 1.04); adjusted HR = 1.01 (95% CI = 0.94;
      1.08). Among the 104 women with HADS-A >= 8 and/or HADS-D >= 8, 34 (32.7%) were
      registered with live birth in MBRN during the period of observation. However, 100
      (27.6%) of the 363 women with both HADS-A <= 7 and HADS-D <= 7 were registered
      with live birth. CONCLUSION: Anxiety and depressive symptoms are not associated
      with probability of live birth in women with self-reported infertility in the
      general population.

PMID- 30190041
TI  - Sleep quality and daytime sleepiness are not associated with cognition in heart
      failure.
AB  - BACKGROUND: Individuals with heart failure (HF) exhibit comorbid impairments in
      both sleep and cognitive performance. Sleep quality has been associated with
      impaired cognitive performance in HF patients, but reports are inconsistent. In
      this study, we examined associations between sleep quality, daytime sleepiness,
      and cognitive function in HF. METHODS AND RESULTS: Participants were 267 (age =
      69.1 +/- 9.3) mostly Caucasian (74.9%), male (59.6%) stable HF patients recruited
      from outpatient settings. This cross-sectional study was a secondary analysis of
      a prospective observational study. Cognitive function domains assessed included:
      global cognitive function, attention, memory, and executive function. Sleep
      quality and daytime sleepiness were assessed using the Pittsburgh Sleep Quality
      Index (PSQI) and the Epworth Sleepiness Scale (ESS), respectively. Separate
      multiple hierarchical linear regressions were conducted to determine associations
      between cognitive function and sleep quality and daytime sleepiness, after
      controlling for sex, New York Heart Association (NYHA) class, education,
      depressive symptoms, and medical comorbidities. Cognitive function was not
      associated with sleep quality or daytime sleepiness after alpha inflation
      corrections were applied. CONCLUSIONS: Cognitive function in HF is not associated
      with sleep quality or daytime sleepiness; other factors may exert greater
      influence on cognitive performance.

PMID- 30190044
TI  - An epidemiologic study of self-reported sleep problems in a large sample of
      adolescent earthquake survivors: The effects of age, gender, exposure, and
      psychopathology.
AB  - BACKGROUND: This study investigated the prevalence of sleep problems and their
      associated risk factors in child and adolescent survivors three years after the
      2013 Ya'an earthquake. METHODS: A total of 6132 adolescent survivors aged 9-18
      years were invited to complete the Pittsburgh Sleep Quality Index, Children's
      Revised Impact of Event Scale-13, Short Mood and Feelings Questionnaire, and
      Screen for Child Anxiety-Related Emotional Disorders. Logistic analysis was used
      to identify possible relationships of sleep disturbance scores with earthquake
      exposures, mental health and demographic characteristics. RESULTS: More than a
      quarter of the sample showed sleep problems of some kind, with 23.1% sleeping
      fewer than 7 h per night, 32.5% having difficulty falling asleep, 24.2% having
      difficulty remaining asleep, 25.3% having poor sleep quality, 17.4% having
      nightmares and 44.6% having difficulty functioning during daytime hours. Older
      participants were at a significantly higher risk of sleep issues than younger
      children (OR 2.89), and the subjects had significantly elevated risks of probable
      anxiety (OR 3.47), probable depression (OR 2.45), and probable posttraumatic
      stress disorder (OR 1.89). Other risk factors for sleep problems were earthquake
      exposure variables, including being injured (OR 1.42), having a parent injured
      (OR 1.27), witnessing death (OR 1.32) or feeling extremely scared (OR 1.22) in
      the Ya'an earthquake. CONCLUSIONS: Sleep disturbances are common in adolescent
      earthquake survivors, and they are associated with age, gender, psychiatric
      symptoms and factors related to earthquake exposure. These results highlight the
      importance of development- and gender-specific interventions to prevent sleep
      disturbances after a major earthquake.

PMID- 30190042
TI  - Investigating post-stroke fatigue: An individual participant data meta-analysis.
AB  - OBJECTIVE: The prevalence of post-stroke fatigue differs widely across studies,
      and reasons for such divergence are unclear. We aimed to collate individual data
      on post-stroke fatigue from multiple studies to facilitate high-powered meta
      analysis, thus increasing our understanding of this complex phenomenon. METHODS:
      We conducted an Individual Participant Data (IPD) meta-analysis on post-stroke
      fatigue and its associated factors. The starting point was our 2016 systematic
      review and meta-analysis of post-stroke fatigue prevalence, which included 24
      studies that used the Fatigue Severity Scale (FSS). Study authors were asked to
      provide anonymised raw data on the following pre-identified variables: (i) FSS
      score, (ii) age, (iii) sex, (iv) time post-stroke, (v) depressive symptoms, (vi)
      stroke severity, (vii) disability, and (viii) stroke type. Linear regression
      analyses with FSS total score as the dependent variable, clustered by study, were
      conducted. RESULTS: We obtained data from 14 of the 24 studies, and 12 datasets
      were suitable for IPD meta-analysis (total n = 2102). Higher levels of fatigue
      were independently associated with female sex (coeff. = 2.13, 95% CI 0.44-3.82, p
      = 0.023), depressive symptoms (coeff. = 7.90, 95% CI 1.76-14.04, p = 0.021),
      longer time since stroke (coeff. = 10.38, 95% CI 4.35-16.41, p = 0.007) and
      greater disability (coeff. = 4.16, 95% CI 1.52-6.81, p = 0.010). While there was
      no linear association between fatigue and age, a cubic relationship was
      identified (p < 0.001), with fatigue peaks in mid-life and the oldest old.
      CONCLUSION: Use of IPD meta-analysis gave us the power to identify novel factors
      associated with fatigue, such as longer time since stroke, as well as a non
      linear relationship with age.

PMID- 30190043
TI  - Psychological distress in patients with an implantable cardioverter defibrillator
      and their partners.
AB  - OBJECTIVES: Adjustment to life with an implantable cardioverter defibrillator
      (ICD) may be challenging for some patients and their partners, with disease and
      individual characteristics likely influencing the process. We examined whether
      perceived social support and clinical patient characteristics are associated with
      change in couples' symptoms of anxiety and depression in the first year after ICD
      implantation, and explored whether the associations differ between patients and
      partners. METHOD: A cohort of consecutively implanted patients (n = 286; 21%
      women) and their partners completed questionnaires on social support and symptoms
      of anxiety and depression prior to ICD implantation and 12 months later.
      Information on demographic and clinical characteristics were captured from
      patients' medical records or purpose-designed questions. Data were analyzed using
      multilevel models accounting for the interdependency of scores within couples
      with adjustment for possible confounders. RESULTS: Higher ratings of perceived
      social support prior to ICD implantation were associated with greater reductions
      in couples' symptoms of anxiety and depression, whereas having received an ICD
      shock was associated with less improvement. Secondary prevention indication for
      ICD implantation and symptomatic heart failure were associated with less
      improvement in anxiety symptoms. These associations applied to both patients' and
      partners' levels of distress. CONCLUSION: The patient's heart disease affects
      both patients' and partners' psychological adjustment in the first year after ICD
      implantation. Interventions are warranted that address this issue not only in
      patients but also in partners. Targeting social support as a resource for both
      could be one avenue to pursue.

PMID- 30190045
TI  - Depressive symptoms predict incident chronic disease burden 10 years later:
      Findings from the English Longitudinal Study of Ageing (ELSA).
AB  - OBJECTIVE: To assess the association between depressive symptoms and incident
      chronic illness burden in prospective longitudinal analyses. METHODS: We analysed
      data from 2472 participants (62.88 +/- 8.49 years old; 50.8% female) from the
      English Longitudinal Study of Ageing (ELSA). Depressive symptoms were measured
      using the Centre for Epidemiological Studies Depression (CES-D) scale at baseline
      in 2004, and participants were followed up for 10 years. Participants with
      prevalent illness at baseline (coronary heart disease [CHD], other cardiac
      illness, stroke, cancer, diabetes/high blood glucose, arthritis, lung disease,
      osteoporosis and Parkinson's disease) were excluded from models predicting
      illness burden (the sum of illnesses reported) over follow-up. Linear regression
      was used controlling for a wide range of covariates. RESULTS: The mean chronic
      illness burden was 0.57, with 43.1% experiencing at least one incident physical
      illness. Baseline continuous CES-D score was a significant predictor of incident
      chronic illness burden up to 10 years later (incident rate ratio = 1.05, 95%
      confidence intervals = 0.05-0.21, p = .003), independent of sociodemographic,
      behavioural, cognitive and clinical covariates. Sensitivity analyses excluding
      participants who developed a chronic illness within the 2 years following
      baseline corroborated the main results. CONCLUSION: Depressive symptoms were
      associated with greater incident chronic illness burden 10 years later. These
      findings have clinical implications for the treatment of depression in physically
      healthy older adults.

PMID- 30190047
TI  - Fecal incontinence in people with self-reported irritable bowel syndrome:
      Prevalence and quality of life.
AB  - Irritable bowel syndrome (IBS) is a common functional gastrointestinal (GI)
      disorder characterized by recurrent abdominal pain and altered bowel habits. IBS
      is a risk factor for fecal incontinence (FI), the unintentional passage of solid
      or liquid stool. FI can substantially interfere with health related quality of
      life (HRQL), leading to heightened anxiety and avoidance behavior. Nevertheless,
      relatively little research has been conducted on the prevalence of FI in IBS
      patients. This study evaluated the prevalence of FI in people with self-reported
      IBS and the relationship between FI and HRQL. 703 people who reported a diagnosis
      of IBS completed questionnaires on IBS symptom severity, FI symptom severity,
      HRQL, fear of food, anxiety about visceral sensations, and GI specific
      catastrophizing. Overall, 60% of people with IBS reported experiencing at least
      one lifetime episode of FI. In a subsample of 360 people who met strict Rome IV
      criteria and reported no other GI related co-morbidities, 62% reported
      experiencing at least one lifetime episode. While people who experienced FI more
      frequently had worse HRQL statistically, the differences in HRQL between people
      who had experienced FI and those who had not were not clinically significant.
      Rather than frequency of FI or physical symptom severity, quality of life was
      mostly determined by psychological variables, such as fear of food, anxiety, and
      catastrophizing. This study suggests that FI is quite prevalent in IBS patients,
      but that the best way to improve HRQL for IBS patients with FI may be to focus on
      reducing anxiety, catastrophizing and avoidance.

PMID- 30190046
TI  - The effect of brief self-management intervention for hemodialysis patients (HED
      SMART) on trajectories of depressive and anxious symptoms.
AB  - OBJECTIVE: Depression is often comorbid with End-Stage Renal Disease, and
      associated with poor adherence and clinical outcomes but course of symptoms is
      variable. This study sought to describe the long-term trajectories of anxiety and
      depression in hemodialysis patients, to identify predictors of these trajectories
      over 12 months and to evaluate the effectiveness of the HEmoDialysis Self
      Management Randomized Trial (HED SMART) against usual care on symptoms of anxiety
      and depression. METHODS: A secondary analysis of data from a randomized
      controlled trial that contrasted HED SMART (n = 101) against usual care (n =
      134). Depressive and anxious symptoms were assessed using the Hospital Anxiety
      and Depression Scale (HADS) at baseline, 1 week and at 3 and 9 months post
      intervention. Latent class growth analysis identified trajectories of depression
      and anxiety, and their sociodemographic and clinical predictors. RESULTS:
      Symptoms of depression and anxiety over 12 months were characterized by two
      trajectories: low stable (depression: 55%; anxiety: 59%) with non-clinical levels
      of distress, and high stable (depression: 45%; anxiety: 41%) with clinical levels
      of distress. HED SMART predicted significant reductions in depression relative to
      usual care. A similar trend was noted for anxiety. Younger age, Chinese
      ethnicity, and more comorbidities were associated with persistent high
      depression. Younger age and shorter dialysis vintage was associated with
      persistent high anxiety. CONCLUSION: A brief self-management intervention
      designed to support behavioral change can also lead to significant reductions in
      symptoms of depression and may be of great value for younger HD patients shown to
      be at greater risk for persistent distress. TRIAL REGISTRATION: ISRTN31434033.

PMID- 30190048
TI  - Differential psychological effects of cognitive-behavioral stress management
      among breast cancer patients with high and low initial cancer-specific distress.
AB  - OBJECTIVE: Cognitive-behavioral stress management (CBSM) improves adaptation to
      primary treatment for breast cancer (BCa), evidenced as reductions in distress
      and increases in positive affect. Because not all BCa patients may need
      psychosocial intervention, identifying those most likely to benefit is important.
      A secondary analysis of a previous randomized trial tested whether baseline level
      of cancer-specific distress moderated CBSM effects on adaptation over 12 months.
      We hypothesized that patients experiencing the greatest cancer-specific distress
      in the weeks after surgery would show the greatest CBSM-related effects on
      distress and affect. METHODS: Stages 0-III BCa patients (N = 240) were enrolled 2
      8 weeks after surgery and randomized to either a 10-week group CBSM intervention
      or a 1-day psychoeducational (PE) control group. They completed the Impact of
      Event Scale (IES) and Affect Balance Scale (ABS) at study entry, and at 6- and 12
      month follow-ups. RESULTS: Latent Growth Curve Modeling across the 12-month
      interval showed that CBSM interacted with initial cancer-related distress to
      influence distress and affect. Follow-up analyses showed that those with higher
      initial distress were significantly improved by CBSM compared to control
      treatment. No differential improvement in affect or intrusive thoughts occurred
      among low-distress women. CONCLUSION: CBSM decreased negative affect and
      intrusive thoughts and increases positive affect among post-surgical BCa patients
      presenting with elevated cancer-specific distress after surgery, but did not show
      similar effects in women with low levels of cancer-specific distress. Identifying
      patients most in need of intervention in the period after surgery may optimize
      cost-effective cancer care.

PMID- 30190049
TI  - Blood pressure recovery to social stress in parentally bereaved and non-bereaved
      youths.
AB  - OBJECTIVE: To examine differences in blood pressure response and recovery in a
      sample of bereaved and non-bereaved youths during an acute stress task conducted
      5 years after time of parental death. METHODS: One-hundred and ninety-two (n =
      192) bereaved and non-bereaved offspring (ages 11-29) participated in an
      adaptation of the Trier Social Stress Task (TSST) 5-years after the time of
      parental death. Blood pressure measurements were collected before, during, and
      after the laboratory stress protocol. Mixed models for repeated measures were
      used to analyze the effects of bereavement status and course of psychiatric
      disorder in the 5-year period after parental death in both offspring and
      caregivers on blood pressure response; linear regression was used to examine
      these associations with blood pressure recovery. RESULTS: Although there were no
      differences across groups in diastolic (DBP) or systolic blood pressure (SBP)
      response to stress, bereaved offspring demonstrated less SBP recovery to the TSST
      as compared to non-bereaved offspring. A significant interaction between
      bereavement status and race, and a marginally significant interaction between
      bereavement status and sex indicated poor SBP recovery for parentally bereaved
      racial/ethnic minority offspring as compared to parentally bereaved Caucasian
      offspring, and for parentally bereaved males compared to parentally bereaved
      females. CONCLUSIONS: Parentally bereaved youths demonstrate blood pressure
      response to social stress tasks similar to that of non-bereaved youths, but
      parentally bereaved ethnic/racial minority youths and parentally bereaved males
      evidence a less complete recovery from the effects of stress. The health
      consequences of poor blood pressure recovery in bereaved youths are discussed.

PMID- 30190050
TI  - Perceived stress and inappropriate coping behaviors associated with poorer
      quality of life and prognosis in patients with ulcerative colitis.
AB  - OBJECTIVE: To explore the effect of perceived stress and coping behaviors on
      quality of life and clinical outcomes in patients with ulcerative colitis.
      METHODS: This is a prospective cohort study in a tertiary inflammatory bowel
      disease center in China. A total of 263 ulcerative colitis patients were enrolled
      consecutively between June 2013 and February 2015. The Perceived Stress Scale,
      the Medical Coping Modes Questionnaire, and the Inflammatory Bowel Disease
      Questionnaire were used to assess perceived stress, medical coping and quality of
      life at baseline. Patients were followed up for hospitalization due to relapse
      over a one-year period. Multivariate analyses were performed to identify whether
      perceived stress and medical coping behavior were related to quality of life and
      hospitalization. RESULTS: Patients with invalid questionnaires (n = 6) and those
      lost to follow-up (n = 28) were excluded. A total of 229 ulcerative colitis
      patients (mean age 40.4 +/- 12.6, 50.7% male) were included in the final
      analysis, and 23 patients had been hospitalized during the one-year follow-up
      period. After adjusting other associated variables, perceived stress (OR: 1.13;
      95% CI: 1.07 to 1.19) and acceptance-resignation behavior (OR: 1.41; 95% CI: 1.21
      to 1.65) were independently associated with poor quality of life. Patients
      scoring highly for acceptance-resignation behavior (OR: 1.23; 95% CI: 1.04 to
      1.46) were more likely to be hospitalized during the one-year follow-up period.
      CONCLUSION: In patients with ulcerative colitis, identifying those who adopted
      more acceptance-resignation behavior and improving their medical coping behavior
      by psychotherapy could be helpful to achieve better quality of life and disease
      control.

PMID- 30190051
TI  - Living with Pernicious Anaemia: exploring the link between anticipated stigma and
      wellbeing.

PMID- 30190052
TI  - Comparing the diagnostic concepts of ICD-10 somatoform disorders and DSM-5
      somatic symptom disorders in patients from a psychosomatic outpatient clinic.
AB  - OBJECTIVE: The reconceptualization of somatic symptom and related disorders in
      DSM-5 led to numerous consequences in terms of prevalence and affected patient
      populations. The present study aimed to investigate frequencies of ICD-10
      somatoform disorders and DSM-5 somatic symptom disorders, and how the respective
      diagnostic groups differ in terms of sociodemographic and psychopathological
      characteristics. It discusses the usefulness and reliability of the new
      diagnostic criteria. METHOD: Patients from a German psychosomatic outpatient
      clinic (n = 438) completed self-report questionnaires on depression (PHQ-9),
      anxiety (GAD-7), symptom burden (PHQ-15), psychological distress (SSD-12), and
      quality of life (SF-12). ICD-10 diagnoses were provided by treating clinicians,
      DSM-5 diagnoses were assessed via semi-structured telephone interviews. The
      prevalence of somatic symptom disorders and their overlap with ICD-10 somatoform
      disorders was evaluated. Comparisons between patients with either diagnosis were
      drawn. RESULTS: More than half of the sample (n = 239, 54.6%) fulfilled the
      criteria for a somatic symptom disorder. Compared to patients fulfilling ICD-10
      criteria only, patients with a somatic symptom disorder presented higher levels
      of symptom related distress (p = .045), health related anxiety (p = .004),
      general anxiety (p = .011), and lower mental health-related quality of life (p =
      .015), while patients with ICD-10 somatoform disorders reported a lower physical
      health-related quality of life (p = .031). CONCLUSION: DSM-5 criteria included
      more patients than ICD-10 somatoform disorders in our sample. Patients diagnosed
      with a somatic symptom disorder appear to be more severely impaired in terms of
      general and health-related anxiety and psychological distress associated to their
      somatic symptoms, especially when diagnosed with a severe form of somatic symptom
      disorder.

PMID- 30190053
TI  - A randomized clinical trial of the Unified Protocol for Transdiagnostic treatment
      of emotional and gastrointestinal symptoms in patients with irritable bowel
      syndrome: evaluating efficacy and mechanism of change.
AB  - OBJECTIVE: The aim of this randomized controlled trial was to evaluate the
      efficacy of Unified Protocol (UP) for transdiagnostic treatment of psychological
      problems, such as anxiety, depression, and stress, and treating the intensity of
      gastrointestinal symptoms in individuals with Irritable Bowel Syndrome (IBS).
      Another aim of the study was to test whether emotion regulation mediates the
      effect of UP. METHODS: Among 91 patients diagnosed with IBS (using ROME III
      criteria), 64 patients were eligible to participate in the study based on the
      inclusion/exclusion criteria. These patients were randomly assigned to either an
      intervention group (n = 32) that participated in 12 weekly UP treatment sessions
      or to a wait-list control group (n = 32). All patients completed the Depression,
      Anxiety, and Stress Scale (DASS-42), Emotion Regulation Questionnaire (ERQ), and
      Gastrointestinal Symptoms Rating Scale (GSRS) pre- and post-intervention. The
      data were analyzed with SPSS 20.0 software. RESULTS: The results of intention-to
      treat (ITT) analysis indicated a significant decrease in depression, anxiety,
      stress, and gastrointestinal symptoms, as well as significant improvements in
      emotion regulation scores in the intervention group post intervention. All
      results were significant at P < .001. Mediation analyses indicated that changes
      in emotion regulation mediated the effect of UP on changes in emotional and
      gastrointestinal symptoms. CONCLUSION: UP was effective and influential in
      emotion regulation among the intervention group and caused a decline in emotional
      and gastrointestinal symptoms. Hence, this intervention is promising, but larger
      RCTs are needed to more investigate its efficacy. Future studies could also
      examine the efficacy of the UP in other medical conditions with co-occurring
      psychological conditions. The study is registered at the irct.ir database under
      registration number IRCT2017010431765N1.

PMID- 30190054
TI  - Attending away from the body predicts increased physical symptom reports at six
      months in primary care patients.
AB  - OBJECTIVE: High symptom reporting (HSR) and medically unexplained symptoms (MUS)
      are associated with considerable distress, disability, healthcare utilization and
      costs, but are poorly understood, and current treatments are of limited benefit.
      Most models of HSR and MUS implicate cognitive-perceptual factors, such as
      increased body-focused attention, reduced perceptual thresholds and a tendency to
      experience somatic misperception, but little is known about the causal role of
      these variables. We investigated this issue by studying whether there is a
      longitudinal relationship between perceptual-attentional variables and later
      clinical outcomes in primary care patients. METHOD: Primary care patients (N =
      102) completed clinical (physical symptom reporting, health anxiety and
      healthcare utilization) and perceptual-attentional (body-focused attention,
      perceptual threshold, somatic misperception) measures at baseline and then again
      six months later (N = 72). Hierarchical regression was used to examine cross
      lagged relationships between baseline and follow-up scores. RESULTS: Contrary to
      expectation, attending away from the body at baseline predicted increased not
      decreased symptom reporting six months later. Neither perceptual threshold nor
      somatic misperception predicted clinical outcomes at six months. CONCLUSIONS:
      These findings suggest that body avoidance, rather than increased body focus,
      contribute to the development of HSR. Future studies should consider the
      potential clinical benefits of reducing bodily avoidance, via techniques that
      promote adaptive engagement with bodily sensations.

PMID- 30190055
TI  - Gender differences in psychosocial outcomes of psychotherapy trial in patients
      with depression and coronary artery disease.
AB  - INTRODUCTION: The biological and psychosocial risk profile differs between women
      and men with coronary artery disease (CAD). Depressive symptoms and Vital
      Exhaustion (VE) predict an unfavourable course of CAD. The secondary analysis of
      the SPIRR-CAD trial offered the possibility to examine gender as exposure
      variable of the clinical and psychological situation at baseline and in a variety
      of psychosocial measures as outcomes. METHODS: In this trial, 450 men (78.9%) and
      120 women (21.1%) with CAD (age <= 75 y), with mild to moderate depression
      (scoring >=8 on the HADS), were randomized to usual care with or without a
      stepwise psychotherapy intervention. Beside clinical measures exhaustion and
      other indicators of depressive symptoms were collected at baseline and 18-month
      follow up. RESULTS: Men had more signs and symptoms of heart disease at baseline,
      whereas women had higher psychosocial burden (e.g. negative affect). Women were
      more likely to live alone, had lower educational levels and employment rates and
      higher levels of depression and exhaustion. The psychotherapy intervention
      differed as a function of gender: In women, VE decreased from 29.4 +/- 8.1 to
      22.1 +/- 11.7 in the intervention group (IG) and from 29.2 +/- 8.2 to 25.1 +/-
      11.3 in the control group (CG). In men VE decreased from 23.3 + -10.8 to 21.2 +/-
      9.7 in the IG and from 23.6 +/- 10.7 to 19.3 +/- 11.3 in the CG (time x
      intervention x gender; F = 4.97; p = .026). DISCUSSION: Women had a higher
      psychosocial burden than men. VE compared to other rating instruments of
      depressive symptoms suggested a stronger response to the intervention in women.
      VE may help to understand gender differences in psychotherapeutic treatment
      studies of CAD. ISRCTN: 76240576; clinicaltrials.gov.

PMID- 30190056
TI  - Editors' Welcome.

PMID- 30190057
TI  - Retraction notice to "Results from a 12 months, randomized, clinical trial
      comparing an olmesartan/amlodipine single pill combination to olmesartan and
      amlodipine monotherapies on blood pressure and inflammatin" [European Journal of
      Pharmaceutical Sciences 51C (2013) 26-33].

PMID- 30190059
TI  - Different Health Care Systems With a Common Message: Experience Has a Major
      Impact on Transcatheter Aortic Valve Replacement Outcomes.

PMID- 30190058
TI  - The Learning Curve and Annual Procedure Volume Standards for Optimum Outcomes of
      Transcatheter Aortic Valve Replacement: Findings From an International Registry.
AB  - OBJECTIVES: The authors aimed to determine the procedural learning curve and
      minimum annual institutional volumes associated with optimum clinical outcomes
      for transcatheter aortic valve replacement (TAVR). BACKGROUND: Transcatheter
      aortic valve replacement (TAVR) is a complex procedure requiring significant
      training and experience for successful outcome. Despite increasing use of TAVR
      across institutions, limited information is available for its learning curve
      characteristics and minimum annual volumes required to optimize clinical
      outcomes. METHODS: The study collected data for patients at 16 centers
      participating in the international TAVR registry since initiation of the
      respective TAVR program. All cases were chronologically ordered into initial (1
      to 75), early (76 to 150), intermediate (151 to 225), high (226 to 300), and very
      high (>300) experience operators for TAVR learning curve characterization. In
      addition, participating institutions were stratified by annual TAVR case volume
      into low-volume (<50), moderate-volume (50 to 100), and high-volume (>100) groups
      for comparative analysis. Procedural and 30-day clinical outcomes were collected
      and multivariate regression analysis performed for 30-day mortality and the early
      safety endpoint. RESULTS: A total of 3,403 patients comprised the study
      population. On multivariate analysis, all-cause mortality was significantly
      higher for initial (odds ratio [OR]: 3.83; 95% confidence interval [CI]: 1.93 to
      7.60), early (OR: 2.41; 95% CI: 1.51 to 5.03), and intermediate (OR: 2.53; 95%
      CI: 1.19 to 5.40) experience groups compared with the very high experience
      operators. In addition, the early safety endpoint was significantly worse for all
      experience groups compared with the very high experience operators. Low annual
      volume (<50) TAVR institutions had significantly higher all-cause 30-day
      mortality (OR: 2.70; 95% CI: 1.44 to 5.07) and worse early safety endpoint (OR:
      1.60; 95% CI: 1.17 to 2.17) compared with the moderate- and high-volume groups.
      There was no difference in patient outcomes between intermediate and high annual
      volume groups. CONCLUSIONS: TAVR procedures display important learning curve
      characteristics with both greater procedural safety and a lower mortality when
      performed by experienced operators. In addition, TAVR performed at low annual
      volume (<50 procedures) institutions is associated with decreased procedural
      safety and higher patient mortality. These findings have important implications
      for operator training and patient care at centers performing TAVR.

PMID- 30190060
TI  - Overexpansion of the SAPIEN 3 Transcatheter Heart Valve: An Ex Vivo Bench Study.
AB  - OBJECTIVES: This study assessed the effect of overexpansion beyond labeled size
      (diameter) of transcatheter heart valves through an ex vivo bench study.
      BACKGROUND: Transcatheter heart valves function optimally when expanded to
      specific dimensions. However, clinicians may sometimes wish to overexpand balloon
      expandable valves to address specific clinical challenges. The implications of
      overexpansion have assumed considerable importance, and objective information to
      guide practice is limited. METHODS: We evaluated SAPIEN 3 transcatheter heart
      valves (Edwards Lifesciences, Irvine, California). Valves (diameters of 23, 26,
      and 29 mm) were expanded to nominal dimensions, and then incrementally
      overexpanded with balloons sized 1-, 2-, and 3-mm larger than the recommended
      diameter. Valves underwent visual, microcomputed tomography, and hydrodynamic
      evaluation at various degrees of overexpansion. RESULTS: SAPIEN 3 valves with
      labeled diameters of 23, 26, and 29 mm could be incrementally overexpanded to
      midvalve diameters of 26.4, 28.4, and 31.2 mm, respectively. With overexpansion,
      there was visible restriction of the valve leaflets, which was particularly
      evident with the smaller valves. After maximal overexpansion of a 26-mm valve a
      leaflet tear was observed. High-speed video demonstrated impaired leaflet motion
      of both the 23- and 26-mm valves and hydrodynamic testing documented a
      regurgitant fraction for the 23- and 26-mm valves above accepted international
      standards. The maximally overexpanded 29-mm SAPIEN 3 still had relatively normal
      leaflet motion and excellent hydrodynamic function. Durability was not
      specifically evaluated. CONCLUSIONS: Overexpansion of balloon-expandable valves
      is possible. However, excessive overexpansion may be associated with impaired
      hydrodynamic function, acute leaflet failure, and reduced durability. Smaller
      valves may be at greater risk with overexpansion than larger valves.
      Overexpansion is best avoided unless clinical circumstances are compelling.

PMID- 30190061
TI  - Optimizing Valve Sizing in Balloon-Expandable Transcatheter Aortic Valve
      Replacement.

PMID- 30190062
TI  - Coming Closer to Personalized Medicine in Transcatheter Aortic Valve Replacement.

PMID- 30190063
TI  - Incidence, Management, and Associated Clinical Outcomes of New-Onset Atrial
      Fibrillation Following Transcatheter Aortic Valve Replacement: An Analysis From
      the STS/ACC TVT Registry.
AB  - OBJECTIVES: The aim of this study was to evaluate incidence, care patterns, and
      clinical outcomes in patients developing new-onset atrial fibrillation (AF)
      following transcatheter aortic valve replacement (TAVR). BACKGROUND: Pre
      procedural AF has been associated with adverse outcomes in patients undergoing
      TAVR, but the incidence of new-onset AF, associated anticoagulant management, and
      subsequent clinical outcomes are unclear. METHODS: Using the Society of Thoracic
      Surgeons/American College of Cardiology TVT (Transcatheter Valve Therapy)
      Registry linked with Medicare claims, patients undergoing TAVR from 2011 to 2015
      who developed post-procedural AF were evaluated. Patients with known AF prior to
      TAVR were excluded. Outcomes of interest included in-hospital mortality and
      stroke and all-cause mortality, stroke, and bleeding at 12 months. Multivariate
      adjustment was then performed to determine differences in 1-year outcomes among
      those with and without new post-procedural AF, stratified by anticoagulation
      status. RESULTS: We identified 1,138 of 13,556 patients (8.4%) who developed new
      onset AF (4.4% of transfemoral [TF]-access patients, 16.5% of non-TF-access
      patients). Patients developing AF were older, more likely female, had higher
      Society of Thoracic Surgeons risk scores, and were often treated using non-TF
      access. Despite having a median CHA2DS2-VASc score of 5 (25th and 75th
      percentile: 5 to 6), only 28.9% of patients with new AF were discharged on oral
      anticoagulation. In-hospital mortality (7.8% vs. 3.4%; p < 0.01) and stroke (4.7%
      vs. 2.0%; p < 0.01) were higher among patients who developed post-procedural AF
      compared with those who did not. At 1 year, rates of death (adjusted hazard ratio
      [HR]: 1.37; 95% confidence interval [CI]: 1.19 to 1.59), stroke (adjusted HR:
      1.50; 95% CI: 1.14 to 1.98), and bleeding (adjusted HR: 1.24; 95% CI: 1.10 to
      1.40) were higher among patients with new-onset AF. One-year mortality rates were
      highest among patients who developed new-onset AF but were not discharged on
      anticoagulation. CONCLUSIONS: Post-TAVR AF occurred in 8.4% of patients (4.4%
      with TF access, 16.5% with non-TF access), with fewer than one-third of patients
      receiving anticoagulation at discharge, and was associated with increased risk
      for in-hospital and 1-year mortality and stroke. Given the clinical significance
      of post-TAVR AF, additional studies are necessary to delineate the optimal
      management strategy in this high-risk population.

PMID- 30190064
TI  - Atrial Fibrillation After Transcatheter Aortic Valve Replacement: Is
      Anticoagulation the Answer?

PMID- 30190066
TI  - The Sooner the Better?: The Doctor Knows Best.

PMID- 30190065
TI  - Early Versus Standard Discharge After Transcatheter Aortic Valve Replacement: A
      Systematic Review and Meta-Analysis.
AB  - OBJECTIVES: This study sought to assess the clinical outcomes of patients
      undergoing transcatheter aortic valve replacement (TAVR) with early discharge
      (ED) versus standard discharge (SD) pathways. BACKGROUND: Minimalist approaches
      for TAVR have been developed targeting different aspects of the procedure such as
      local anesthesia or sedation, intraprocedural imaging, vascular access, post
      operative monitoring and care, and discharge planning. Their incorporation into
      routine clinical practice aims to reduce length of hospital stay and health care
      cost utilization without adversely affecting outcomes when compared with standard
      approaches. METHODS: The authors conducted a search of MEDLINE and EMBASE to
      identify studies that investigated ED (<=3 days) versus SD in TAVR patients.
      Random-effects meta-analyses were used to estimate the effect of ED compared with
      SD with regard to 30-day mortality after discharge, 30-day readmission rate, and
      need for permanent pacemaker implantation (PPI) following discharge. RESULTS:
      Eight studies including 1,775 participants (ED, n = 642) fulfilled the inclusion
      criteria. The mean age was 82.4 years and STS score was 6.7. Meta-analyses
      evaluating discharge to 30-day mortality (odds ratio [OR]: 0.65; 95% confidence
      interval [CI]: 0.23 to 1.82; I2 = 0%) and discharge to 30-day new PPI (OR: 1.61;
      95% CI: 0.19 to 13.71; I2 = 40%) showed no significant difference in an ED
      compared with a SD strategy. Notably, ED patients were less likely to be
      readmitted after ED when compared with SD patients (OR: 0.63; 95% CI: 0.41 to
      0.98; p = 0.04, I2 = 0%). CONCLUSIONS: ED following uncomplicated TAVR is safe in
      terms of discharge to 30-day mortality or need for PPI following discharge.
      Moreover, ED patients experienced a lower rate of readmissions. These data
      support the safety of programs aiming an ED pathway in selected TAVR patients.
      Institutional protocols with the input from different members of the
      multidisciplinary heart team should be devised to optimize discharge processes to
      improve health care resource utilization.

PMID- 30190068
TI  - Reply: Pleiotropic Effects of Ticagrelor Beyond Its Potent Antiplatelet Effects
      Contributing to Additional Clinical Benefits.

PMID- 30190067
TI  - Real-Time Monitoring of von Willebrand Factor in the Catheterization Laboratory:
      The Seatbelt of Mini-Invasive Transcatheter Aortic Valve Replacement?
AB  - Significant paravalvular regurgitation (PVR) remains a relatively frequent (4% to
      9%) and deleterious complication of transcatheter aortic valve replacement
      (TAVR), even with the latest generation of bioprosthesis. Although mini-invasive
      TAVR without general anesthesia or transesophageal echocardiography (TEE) is
      progressively becoming the predominant approach, identification and grading of
      PVR in the catheterization laboratory remain an important and challenging
      clinical issue. The authors discuss how a recently reported blood biomarker
      reflecting the von Willebrand factor activity, that is, the closure time with
      adenosine diphosphate, can be successfully applied during the TAVR procedure to
      detect and monitor PVR in real time, with an excellent negative predictive value.
      This point-of-care testing performed directly in the catheterization laboratory
      may improve the diagnosis of PVR and rationalize the decision of whether or not
      to perform corrective measures. They further discuss how such a test could be a
      substitute for the multimodal approach combining TEE, hemodynamics, and cine
      angiography, and help to secure the transition to the mini-invasive approach and
      facilitate the expanding indications of less invasive procedures to lower-risk
      patients without jeopardizing procedural and clinical outcomes.

PMID- 30190069
TI  - Pleiotropic Effects of Ticagrelor Beyond its Potent Antiplatelet Effects
      Contributing to Additional Clinical Benefits.

PMID- 30190070
TI  - Superficial Femoral Artery Recanalization via Transradial Access or a Combined
      Radial-Pedal Access Strategy.

PMID- 30190071
TI  - Reply: Superficial Femoral Artery Recanalization Via a Transradial Access or a
      Combined Radial-Pedal Access Strategy.

PMID- 30190072
TI  - Supra-Annular Sizing for Transcatheter Aortic Valve Replacement Candidates With
      Bicuspid Aortic Valve.

PMID- 30190073
TI  - Year 1: A Short Look Back and a Long Look Forward.

PMID- 30190074
TI  - Comparison of Outcomes of Transfemoral Versus Transapical Approach for
      Transcatheter Aortic Valve Implantation.
AB  - Post hoc analyses of clinical trials have shown superior outcomes for a
      transfemoral (TF) compared with a transapical (TA) approach for transcatheter
      aortic valve implantation (TAVI). There are few contemporary data on utilization
      and outcomes of TF versus TA TAVI in real-world patient populations. Using the
      National Inpatient Sample 2011 to 2014, we identified TF-TAVI and TA-TAVI
      procedures using ICD-9 procedure codes 35.05 and 35.06, respectively. A
      propensity-matched cohort of TF and TA TAVI procedures balanced on 23 baseline
      characteristics was assembled. Outcomes included in-hospital mortality, acute
      kidney injury (AKI), AKI requiring dialysis (AKI-D) and postoperative stroke. A
      total of 7,973 TAVI procedures representative of 39,745 procedures nationally
      were included in the study. Of these, 80.2% were performed using a TF approach
      while 19.8% used a TA approach. Patients in the TF-TAVI group were older (mean
      age 81.7 vs 80.4 years, p < 0.001), with a higher prevalence of heart failure
      (12.7% vs 7.6%, p < 0.001) and lower prevalence of peripheral vascular disease
      (28.0% vs 35.5%, p < 0.001) compared with the TA-TAVI group. In 1,576 propensity
      matched pairs of TF-TAVI and TA-TAVI procedures, TF-TAVI was associated with
      significantly lower in-hospital mortality (odds ratio [OR] 0.61, 95% confidence
      interval [CI] 0.42 to 0.88, p = 0.01), lower rates of AKI (0.53, 95% CI 0.44 to
      0.63, p < 0.001), similar rates of AKI-D (OR 0.77, 95% CI 0.44 to 1.38, p = 0.38)
      and postoperative stroke (OR 1.19, 95% CI 0.67 to 2.10, p = 0.56) compared with
      TA-TAVI. In conclusion, TF-TAVI is associated with lower rates of in-hospital
      mortality and AKI compared with TA-TAVI. A TF approach should be preferred over a
      TA approach for TAVI whenever possible.

PMID- 30190075
TI  - Current and prospective therapies for acute liver failure.

PMID- 30190076
TI  - Internal Limiting Membrane Peeling in Macula-Off Retinal Detachment Complicated
      by Grade B Proliferative Vitreoretinopathy.

PMID- 30190077
TI  - A targeted initiative to discharge surgical patients earlier in the day is
      associated with decreased length of stay and improved hospital throughput.
AB  - BACKGROUND: The timing of inpatient discharges can impact hospital throughput
      with later discharges leading to decreased patient satisfaction, increased length
      of stay (LOS), and longer boarding times. METHODS: A 12-month targeted
      intervention that included both pre-operative and inpatient components was
      implemented across all surgical inpatient services to increase the proportion of
      patients discharged by noon. RESULTS: Discharge by noon rates increased from
      14.3% to 21.5% during the 12-month initiative (p < 0.01). The case mix index
      adjusted LOS (aLOS) decreased from 2.17 to 2.02 days (p < 0.01). ED, PACU, and
      ICU boarding times were all significantly lower during the initiative (p < 0.01,
      p < 0.01, p = 0.03 respectively). CONCLUSIONS: A targeted initiative to discharge
      surgical patients earlier resulted in a 50% increase in the proportion of
      patients discharged by noon. Associated with this finding were improvements in
      hospital throughput as measured by aLOS and boarding times in the ED, ICUs, and
      PACU.

PMID- 30190078
TI  - Prospective validation of the Parkland Grading Scale for Cholecystitis.
AB  - BACKGROUND: The Parkland Grading Scale for Cholecystitis (PGS) was developed as
      an intraoperative grading scale to stratify gallbladder (GB) disease severity
      during laparoscopic cholecystectomy (LC). We aimed to prospectively validate this
      scale as a measure of LC outcomes. METHODS: Eleven surgeons took pictures of and
      prospectively graded the initial view of 317 GBs using PGS while performing LC
      (LIVE) between 9/2016 and 3/2017. Three independent surgeon raters
      retrospectively graded these saved GB images (STORED). The Intraclass Correlation
      Coefficient (ICC) statistic assessed rater reliability. Fisher's Exact,
      Jonckheere-Terpstra, or ANOVA tested association between peri-operative data and
      gallbladder grade. RESULTS: ICC between LIVE and STORED PGS grades demonstrated
      excellent reliability (ICC = 0.8210). Diagnosis of acute cholecystitis,
      difficulty of surgery, incidence of partial and open cholecystectomy rates, pre
      op WBC, length of operation, and bile leak rates all significantly increased with
      increasing grade. CONCLUSIONS: PGS is a highly reliable, simple, operative based
      scale that can accurately predict outcomes after LC. TABLE OF CONTENTS SUMMARY:
      The Parkland Grading Scale for Cholecystitis was found to be a reliable and
      accurate predictor of laparoscopic cholecystectomy outcomes. Diagnosis of acute
      cholecystitis, surgical difficulty, incidence of partial and open cholecystectomy
      rates, pre-op WBC, operation length, and bile leak rates all significantly
      increased with increasing grade.

PMID- 30190079
TI  - Understanding patient expectations around therapeutic benefits, risks, and the
      chance of cure.
AB  - Conversations around surgical goals of care should focus on relational (e.g.,
      empathy, trust, understanding) instead of transactional processes (e.g.,
      communication). Rather than reducing the patient-surgeon relationship to isolated
      variables such as "communication," a "relational lens" that considers all the
      aspects of the patient-surgeon relationship and its dynamic processes is needed.

PMID- 30190080
TI  - Ensuring selectivity using retention time modulation by solvent composition,
      applied to the analysis of phenol in e-liquids.
AB  - A gas chromatographic method for the determination of volatile contaminants
      (halogenated solvents, benzene, toluene, ethyl-benzene, xylenes, styrene) and
      phenol in e-liquids was developed and validated with a working range of 0.01
      (limit of quantification) to 0.5 mg/l, and variation coefficients between 2 and
      14%. Selectivity performing MS/MS-detection was sufficient for all analytes
      except for phenol: e-liquids contain high amounts of aroma compounds in excess of
      105 compared to phenol. A number of these compounds potentially interfere at the
      retention time of phenol, showing all masses (including daughter ions and
      transitions) of phenol. To allow the detection of phenol in this matrix, a novel
      approach of adding a polar molecule to the injection solvent was used, modulating
      the polarity of the column, and thus the retention time of phenol. By adding 3
      MUl/ml and 10 MUl/ml of 1,2-propanediol the retention time of phenol was shifted
      by 0.06 and 0.11 min respectively, while interfering peaks have not been shifted.
      This allowed a reliable confirmation of the presence of phenol. The introduced
      approach is an easy way to generate an additional chromatographic dimension for
      confirmation purposes, not requiring additional equipment.

PMID- 30190082
TI  - Repetitive trunk loading leads to faster trunk movement in response to external
      perturbation.
AB  - The purpose of the present study was to examine trunk movement pattern responses
      to mechanical perturbation before and after two different repetitive trunk
      flexion-extension loading schemes. Spatial and temporal parameters were studied
      to understand the trunk recovery from an anteriorly directed perturbation.
      Eighteen male and female subjects (18-27 yrs) participated in active and passive
      trunk flexion-extension, performed seven days apart. Subjects performed 60 trunk
      flexion-extension repetitions in each condition. Subjects either volitionally
      moved their trunks (active condition) or relaxed while a dynamometer controlled
      the movements (passive condition). Trunk perturbations occurred before and
      immediately after two 30 repetition sessions. Initial responses included latency
      measures of trunk displacement and peak trunk velocity (VP). Temporal measures
      included perturbation onset to initial trunk movement (TD), movement initiation
      to VP (TMIPV), and perturbation onset to VP (TPPV). Recovery measures included
      peak recovery velocity (VPR), recovery time (TR), velocity slope (VS), and
      recovery slope (RS). Differences between loading sessions were present for TPPV
      (p < .05), TR (p < .05), and RS (p < .05). Overall, the results indicate
      repetitive loading leads to lower resistance to perturbation, but faster recovery
      from perturbation although no differences to active or passive repetitive loading
      was observed.

PMID- 30190081
TI  - Simultaneous densitometric determination of eight food colors and four sweeteners
      in candies, jellies, beverages and pharmaceuticals by normal-phase high
      performance thin-layer chromatography using a single elution protocol.
AB  - The present work describes a novel application of high performance thin-layer
      chromatography for the separation and quantification of eight food colors
      (amaranth, allura red, erythrosine, fast green, indigo carmine, quinoline yellow,
      sunset yellow and tartrazine) and four intense sweeteners (acesulfame, aspartame,
      saccharin and neohesperidin) using a single mobile phase. The analyte zones were
      detected densitometrically at 210, 295, 450 and 550 nm. The best chromatographic
      performance for all the additives was achieved using acetonitrile: water: ethyl
      acetate: 10% aqueous ammonia (9:1:1:1, v/v/v/v) as the solvent system within 20
      min. The developed method was validated as per International Conference on
      Harmonization (ICH) guidelines for linearity, sensitivity, selectivity, accuracy
      (recovery), precision (repeatability and reproducibility), robustness and
      stability. The limit of detection and limit of quantitation ranged from 0.2 to
      9.8 ng/zone and 0.7-29.7 ng/zone respectively and the correlation coefficient (
      r2) values for the calibration curves were >= 0.9973 for all the additives. The
      developed method was successfully applied to determine food colors and sweeteners
      in candies, jellies, beverages and pharmaceuticals with minimal sample
      processing. The recovery of different additives obtained from food products,
      beverages and pharmaceuticals ranged from 96.6 to 106.7 %. The results showed
      that all the samples contained food additives within the permissible limits. The
      developed method is simple, precise, accurate and economical for routine quality
      control of foodstuffs.

PMID- 30190084
TI  - Dynamic output feedback-based fault-tolerant control design for T-S fuzzy systems
      with model uncertainties.
AB  - This paper is concerned with fault-tolerant control (FTC) for a class of
      nonlinear discrete-time systems. A dynamic output feedback controller is designed
      for Takagi-Sugeno (T-S) fuzzy systems with state and input parameter
      uncertainties, exogenous disturbances, measurement noise and multiple
      intermittent faults. Compared with the existing research results, the proposed
      controller has a wider application range. The stability of the closed-loop
      systems is guaranteed by Hinfinity performance and sufficient conditions are
      proposed for the considered system with multiple sensor faults, multiple actuator
      faults, multiple sensor and actuator faults, respectively, by solving linear
      matrix inequalities (LMIs). Finally, two numerical examples are provided to
      demonstrate the effectiveness of the proposed FTC method in the paper.

PMID- 30190083
TI  - Numerical simulation of aneurysmal haemodynamics with calibrated porous-medium
      models of flow-diverting stents.
AB  - Modelling flow-diverting (FD) stents as porous media (PM) markedly improves the
      efficiency of computational fluid dynamics (CFD) simulations in the study of
      intracranial aneurysm treatment. Nonetheless, the parameters of PM models adopted
      for simulations up until now were rarely calibrated to match the represented FD
      structure. We therefore sought to evaluate the PM parameters for a representative
      variety of commercially available stents, so characterising the flow-diversion
      behaviours of different FD devices on the market. We generated fully-resolved
      geometries for treatments using PED, Silk+, FRED, and dual PED stents. We then
      correspondingly derived the calibrated PM parameters-permeability (k) and
      inertial resistance factor (C2)-for each stent design from CFD simulations, to
      ensure the calibrated PM model has identical flow resistance to the FD stent it
      represents. With each of the calibrated PM models respectively deployed in two
      aneurysms, we studied the flow-diversion effects of these stent configurations.
      This work for the first time reported several sets of parameters for PM models,
      which is vital to address the current knowledge gap and rectify the errors in PM
      model simulations, thereby setting right the modelling protocol for future
      studies using PM models. The flow resistance parameters were strongly affected by
      porosity and effective thickness of the commercial stents, and thus accounted for
      in the PM models. Flow simulations using the PM stent models revealed differences
      in aneurysmal mass flowrate (MFR) and energy loss (EL) between various stent
      designs. This study improves the practicability of FD simulation by using
      calibrated PM models, providing an individualised method with improved simulation
      efficiency and accuracy.

PMID- 30190085
TI  - Dysfunctional RNA binding proteins and stress granules in multiple sclerosis.
AB  - Dysfunction of the RNA binding protein (RBP) heterogeneous nuclear ribonuclear
      protein A1 (hnRNP A1) has been shown to contribute to the pathogenesis of
      neurodegenerative diseases, but its involvement in multiple sclerosis (MS) is
      largely unknown. In a neuronal cell line, interferon-gamma caused hnRNP A1
      nucleocytoplasmic mislocalization; colocalization of hnRNP A1 in stress granules
      (SGs); and inhibition of translation. Neurons in the brain of a MS patient showed
      pathogenic RBP dysfunction, including nuclear depletion of hnRNP A1, its
      mislocalization to the cytoplasm, and its colocalization in SGs. These data
      indicate a role for dysfunctional hnRNP A1 in the pathogenesis of MS.

PMID- 30190086
TI  - Experimental sepsis induces sustained inflammation and acetylcholinesterase
      activity impairment in the hypothalamus.
AB  - Sepsis is one of the leading causes of mortality in intensive care units besides
      causing profound alterations in the brain. One of the structures notably affected
      during sepsis is the hypothalamus, resulting in important physiopathological
      consequences. Recently, we provided evidence that the presence of
      neuroinflammation, oxidative stress, and apoptosis in the hypothalamus of septic
      rats, is accompanied by impairment of arginine vasopressin (AVP) secretion. We
      had also demonstrated that sepsis survivor animals present attenuated AVP
      secretion after osmotic challenge, suggesting a persistent inflammation in the
      hypothalamus. However, the long-term course of inflammation in the hypothalamus
      remains unclear. Thus, we induced sepsis by cecal ligation and puncture (CLP) in
      Wistar rats and, five days after sepsis induction, the hypothalamus of each
      animal was collected for analysis. Nonmanipulated animals (naive) were used as
      controls. We found that CLP-induced morphological alterations in microglial cells
      are accompanied by an increase in Iba-1 immunoreactivity. Moreover, we observed
      enhanced expression of NF-kappaB and CREB transcription factors, which are well
      known to modulate the immune response. Additionally, we found that
      phosphorylation of GSK3alpha/beta (a kinase upstream to the CREB signaling
      pathway) was increased, as well as COX-2, iNOS, and IL-6 that are canonic
      inflammatory proteins. Thus, our results indicated the presence of sustained
      activation of resident glial cells that may result in neuroinflammation and
      cholinergic neurotransmission disruptions in the hypothalamus.

PMID- 30190087
TI  - An ethical appraisal of living-anonymous kidney donation using Adam Smith's
      Theory of Moral Sentiments.
AB  - Ethical debates continue to shape organ transplant policies, particularly for
      kidneys. Facing organ shortages, governments have created incentives targeting
      prospective living-anonymous donors - socially and biologically unrelated to the
      recipient. However, these policies may transform altruistic exchanges of tissues
      into trades of commodities. We use Adam Smith's concept of sympathy to outline a
      new approach to transplantation ethics. This is accomplished using a case study
      analysis of six countries with established living-anonymous kidney donation
      practices - Iran, Israel, the Netherlands, Saudi Arabia, the United Kingdom, and
      the United States. An ethical test was also developed from ethnographies of
      donors and Smith's Theory of Moral Sentiments. The case study analysis considered
      the role of religious and historic norms, media campaigns, adherence to the 2008
      Declaration of Istanbul guidelines for each case, and how each factor related to
      Smith's sympathy, categorizing the countries into four tiers of altruism. Iran
      occupied the least altruistic tier, followed by the Netherlands, the UK and the
      US, and Saudi Arabia and Israel. The ethical test identified a similar ranking.
      Our findings suggest that a highly-selected cohort of states with established
      living-anonymous kidney donation programs may already utilize a Smithian approach
      for recruiting donors, and that socially-valued government incentives can
      preserve altruism. The ethical test could become a useful instrument to assess
      the altruism of emerging incentive policies.

PMID- 30190088
TI  - Molecular pathogenesis of proliferative verrucous leukoplakia: a systematic
      review.
AB  - Proliferative verrucous leukoplakia (PVL) is a potentially premalignant lesion
      that undergoes malignant transformation in over 40% of cases. Its clinical
      homogeneity suggests that a single or a small number of molecular pathogenic
      pathways may exist. Using the Cochrane protocol for systematic reviews, we have
      looked at the reported evidence of the molecular aetiology and pathogenesis of
      PVL and compared it with that of conventional oral epithelial dysplasia (OED). Of
      the 43 papers studied, 19 met the inclusion criteria including 13 proteins
      assayed in 344 tissues, and genes investigated were TP53, p14ARF, and p16INK4A.
      In all studies the research objectives were defined and outcomes were clearly
      stated. This review has shown that the transformation of PVL does not follow the
      same pathway as that of OED. There was weak evidence to suggest possible
      correlations between DNA aneuploidy, loss of heterozygosity at locus 9p21, and
      specific expression of Mcm (mini chromosome maintenance) protein, to
      transformation of PVL. To show important or distinct pathways of this condition,
      further studies are needed to access the somatic genomic alterations that are
      found in malignancies.

PMID- 30190089
TI  - Orthodromic transfer of the temporalis tendon with extension of the fascia lata
      to reanimate the smile in facial palsy.

PMID- 30190090
TI  - Innovative use of a stereolithographic model together with the mirror image
      technique to reconstruct a defect in mandibular continuity.

PMID- 30190091
TI  - Public knowledge, attitudes and willingness regarding bystander cardiopulmonary
      resuscitation: A nationwide survey in Taiwan.
AB  - BACKGROUND: A low bystander cardiopulmonary resuscitation (CPR) rate is one of
      the factors associated with low cardiac arrest survival. This study aimed to
      assess knowledge, attitudes, and willingness towards performing CPR and the
      barriers for implementation of bystander-initiated CPR. METHODS: Telephone
      interviews were conducted using an author-designed and validated structured
      questionnaire in Taiwan. After obtaining a stratified random sample from the
      census, the results were weighted to match population data. The factors affecting
      bystander-initiated CPR were analysed using logistic regression. RESULTS: Of the
      1073 respondents, half of them stated that they knew how to perform CPR
      correctly, although 86.7% indicated a willingness to perform CPR on strangers.
      The barriers to CPR performance reported by the respondents included fear of
      legal consequences (44%) and concern about harming patients (36.5%). Most
      participants expressed a willingness to attend only an hour-long CPR course.
      Respondents who were less likely to indicate a willingness to perform CPR were
      female, healthcare providers, those who had no cohabiting family members older
      than 65 years, those who had a history of a stroke, and those who expressed a
      negative attitude toward CPR. CONCLUSION: The expressed willingness to perform
      bystander CPR was high if the respondents possessed the required skills. Attempts
      should be made to recruit potential bystanders for CPR courses or education,
      targeting those respondent subgroups less likely to express willingness to
      perform CPR. The reason for lower bystander CPR willingness among healthcare
      providers deserves further investigation.

PMID- 30190092
TI  - Factors increasing the detection rate of intrauterine lesions on hysteroscopy in
      infertile women with sonographically normal uterine cavities.
AB  - BACKGROUND: Detection of intrauterine lesions is important for infertile women,
      as the uterine cavity is the site for embryo growth. This study aims to
      investigate factors that increase the detection rate of intrauterine lesions on
      office hysteroscopy in infertile women with sonographically normal uterine
      cavities. METHODS: We retrospectively enrolled 1726 infertile women who had
      normal uterine cavities on two-dimensional transvaginal sonography. Office
      hysteroscopy was performed in the early proliferative phase of the menstrual
      cycle. RESULTS: Intrauterine lesions were detected in 260 (15.1%) of the 1726
      women. In women who suffered from abnormal uterine bleeding (AUB), hypomenorrhea
      or had a history of dilation and curettage (D&C), the detection rates of
      intrauterine lesions on office hysteroscopy were 41.4%, 22.2% and 19.4%,
      respectively. The predictive rate of abnormal hysteroscopic finding was 22.4% in
      women with at least one of these three clinical features, while it was 9.6% in
      those without. CONCLUSION: AUB, hypomenorrhea, and previous D&C are the three
      factors that increase the detection rate of intrauterine lesions on office
      hysteroscopy in infertile women with sonographically normal uterine cavities.

PMID- 30190093
TI  - Airflow Vibrato: Dependence on Pitch and Loudness.
AB  - OBJECTIVE: To describe the airflow vibrato characteristics at various pitches and
      loudness levels during vocal vibrato production. METHOD: This descriptive case
      series research design included four subjects: 1 baritone, 1 tenor, and 2
      sopranos. The extent and rate of airflow vibrato and fundamental frequency
      vibrato were measured by analyzing /pa:pa:pa:p/ strings with at least 3-4 cycles
      of vibrato during the vowels. Comparison was made within and between the subjects
      at different pitches and loudness levels. RESULT: Airflow vibrato was quite
      evident for all subjects. Mean airflow vibrato extents were larger in female than
      male singers. Increase in airflow vibrato extent was observed with increase in
      pitch, and it was statistically significant when comparison was made within each
      subject, within males (for P2, M = 74.55 cc/s, S.D = 27.44 cc/s, p < 0.01),
      within females (for P2, M = 94.36 cc/s, S.D = 24.13 cc/s, p< 0.01), and between
      males & females (for P1 in females, M = 46.96 cc/s, S.D = 16.16 cc/s, p < 0.003;
      for P2 in females, M = 94.365 cc/c, S.D = 24.13 cc/s, p < 0.02). Statistically
      significant increase in airflow vibrato extent was observed between males and
      females only at the highest loudness level (for females, M = 81.77 cc/s, S.D =
      23.80 cc/s, p < 0.0001). The range of phase difference between them was 34o 
      197o, and most of the time, airflow vibrato lead F0 vibrato. EGG values were also
      reported. CONCLUSION: This study shows that the characteristics of airflow
      vibrato are similar to F0 vibrato; i.e., airflow vibrato also has extent, rate,
      regularity, and waveform complexity. However, airflow vibrato waveforms were seen
      to be more complex in waveshape than F0 vibrato waveforms. Studies on the sources
      of airflow vibrato are necessary.

PMID- 30190094
TI  - Global strain and dyssynchrony of the single ventricle predict adverse cardiac
      events after the Fontan procedure: Analysis using feature-tracking cine magnetic
      resonance imaging.
AB  - BACKGROUND: The aim of this study was to determine whether major adverse cardiac
      events (MACE) during the late phase of the Fontan procedure could be predicted by
      strain measurements of single ventricles using cardiac magnetic resonance imaging
      with feature tracking (CMR-FT). METHODS: One hundred adolescent patients who
      underwent the Fontan procedure (mean age, 21 years) were examined retrospectively
      with CMR-FT to assess the systemic single-ventricle function. Vertical long-axis
      cine imaging was divided into six myocardial segments. Global longitudinal strain
      (GLS) was determined by averaging the peak strain values of each of the six
      segments. The dyssynchrony index was defined as the standard deviation of the
      time to peak strain for six segments. The primary outcome was MACE, defined as
      cardiac death and unscheduled hospitalization. RESULTS: MACE occurred in 18
      patients during a mean follow-up of 62 months. According to the multivariate
      logistic regression analysis results for potential predictor variables, GLS and
      the dyssynchrony index are independent predictors of MACE. Patients with GLS
      >=11.8% had significantly higher MACE-free rates than did those with GLS <11.8%
      [log-rank value, 14.15; p = 0.0002; hazard ratio, 6.82; 95% confidence interval
      (CI), 2.51-18.56]. Patients with a dyssynchrony index <63.5 ms had significantly
      higher MACE-free rates than did those with dyssynchrony index >=63.5 ms (log-rank
      value, 28.17; p < 0.0001; hazard ratio, 21.69; 95% CI, 6.96-67.56). CONCLUSION:
      GLS and the dyssynchrony index found using CMR-FT are independent predictors of
      MACE for adolescent patients after the Fontan procedure and provide information
      regarding risk stratification beyond clinical parameters and biomarkers.

PMID- 30190095
TI  - Ultrasound elastography of the patellar tendon in young, asymptomatic sedentary
      and moderately active individuals.
AB  - BACKGROUND: The recent use of ultrasound elastography to study patellar tendon
      softness has demonstrated increased tendon softness in high-level athletes. We
      hypothesized that measurable alterations in patellar tendon softness may be
      present in young asymptomatic subjects engaging in moderate levels of physical
      activity. METHODS: This was a cross-sectional study. Gray-scale ultrasound and
      ultrasound elastography of the right and left patellar tendons were performed in
      young asymptomatic sedentary subjects and moderately active subjects who engaged
      in at least 30 min of physical activity 4-5 times weekly. The distribution of
      soft, intermediate and stiff tissue within each tendon was analyzed. Tendon
      softness was correlated with subject age, gender and level of athletic activity.
      RESULTS: Sixty patellar tendons in 30 subjects were evaluated (18 males, 12
      females, mean age 22.5 years). Seventeen subjects were defined as "active" and 13
      as "sedentary." All tendons had a normal gray-scale sonographic appearance.
      Tendon softness was significantly higher in active subjects (P = 0.01) and
      decreased with age (P = 0.04). In sedentary individuals there was no significant
      correlation between age and tendon softness (P = 0.404). Similarly, gender showed
      no correlation with tendon softness (P > 0.05). CONCLUSIONS: Patellar tendon
      softness is higher in young subjects and in those engaging in moderate physical
      activity. This may reflect an adaptation to increased tendon load. Tendon
      softness in active subjects decreases with age, while it remains at a constant
      value in sedentary individuals. LEVEL OF EVIDENCE: Level 3.

PMID- 30190096
TI  - Resveratrol increases serum adiponectin level and decreases leptin and insulin
      level in an experimental model of hypercholesterolemia.
AB  - Serum adiponectin concentration is inversely associated with leptin and insulin
      concentration. There is little paucity of information in the literature on the
      adipokine levels and regulation by resveratrol in cholesterol diet-fed animals.
      Thirty rabbits were randomly divided into six groups, each of five animals: Group
      1 = control (C), Group 2 = cholesterol diet (CD) only, Group 3 = resveratrol 200
      mg/kg (R200), Group 4 = resveratrol 400 mg/kg (R400), Group 5 = CD + R200, Group
      6 = CD + R400. The preparations were administered for 8th weeks of the treatment
      protocol. weight and blood glucose level were measured on week zero and the 8th
      week of the treatment. At the end of the study period, the rabbits were placed
      under light anaesthesia. Blood samples were evaluated for serum concentrations of
      metabolites assays (adiponectin, leptin and insulin). Serum adiponectin
      significantly (P < 0.05) increased in resveratrol + CD groups, compared to CD
      group only. Leptin and insulin significantly (P <0.05) decreased in CD groups co
      administered with resveratrol, compared with CD group only. In conclusion, the
      increase in adiponectin level and decrease in leptin and insulin level following
      resveratrol administration elucidated the therapeutic potential of resveratrol,
      despite cholesterol diet consumption.

PMID- 30190097
TI  - Subcutaneous infection with dematiaceous fungi in Card9 knockout mice reveals
      association of impair neutrophils and Th cell response.

PMID- 30190098
TI  - Anaphylaxis to xylitol diagnosed by skin prick test and basophil activation test.

PMID- 30190099
TI  - Typologies of adolescent activity related health behaviours.
AB  - OBJECTIVES: To identify typologies of activity-related behaviours and demographic
      characteristics of these typologies among Australian adolescents. DESIGN: Cross
      sectional study of 473 Secondary School students (41.4% boys, mean age 14.95+/
      1.61 years) conducted in 2014-15. METHODS: Active travel to school, sport
      participation, leisure-time sedentary and demographic variables were self
      reported in a survey. Duration of sedentary time and moderate-to-vigorous
      physical activity (mins/day) were accelerometer-derived. Latent class analysis
      (LCA) was conducted to identify typologies of activity-related health behaviours.
      One-way ANOVAs and chi-square tests were used to explore differences by
      demographic characteristics. RESULTS: Three typologies were identified: (1)
      "Physically inactive, highly sedentary" (44%); (2) "Moderately active, high
      screen-time" (42%); and (3) "Highly active, low sedentary" (14%). Differences
      between typologies were evident for age, sex, body mass index (BMI), cultural
      identity, employment status and socioeconomic position (SEP). Those in typology 3
      (optimal behaviour pattern) tended to be younger, of higher SEP and lower BMI.
      CONCLUSIONS: This study found that older adolescents have less active, more
      sedentary profiles than younger adolescents. The findings support the need for
      targeted interventions to improve adolescent activity-related behaviour
      engagement.

PMID- 30190100
TI  - ProjectRun21: Do running experience and running pace influence the risk of
      running injury-A 14-week prospective cohort study.
AB  - OBJECTIVES: The health benefits from participation in half-marathon is challenged
      by a yearly running-related injury (RRI) incidence proportion exceeding 30%.
      Research in injury etiology is needed to successfully prevent injuries. The
      body's load capacity is believed to play an essential role for injury
      development. Therefore, the purpose of ProjectRun21 was to investigate the
      association between load capacity defined as running experience and running pace,
      and RRI when following a specific half-marathon running schedule. DESIGN: A 14
      week prospective cohort study. METHODS: A cohort of 784 healthy runners followed
      a specific half-marathon running schedule. Data on running activity was collected
      objectively using a Global-Positioning-System watch or smartphone. RRI were
      collected using e-mail-based weekly questionnaires. Primary exposures were
      running experience and running pace, dichotomized into a high and a low group for
      runners running less or more than 15km/week and faster or slower than 6min/km,
      respectively. Data was analyses through time-to-event models with cumulative risk
      difference (RD) as measure of association. RESULTS: A total of 136 participants
      sustained a RRI during follow-up. Although not statistically significant, all
      estimates indicate a tendency toward fewer injuries amongst runners categorized
      as having high experience (RD=-11.3% (-27.2% to 4.6%)) or high pace (RD=-17.4% (
      39.0% to 4.5%)), and a combination of both high experience and high pace (RD=
      8.1% (-22.3% to 6.1%)) compared with their counterpart peers. CONCLUSIONS:
      Runners covering less than 15km per week, and/or runs slower than 6min/km, may
      sustain more RRI than their counterpart runners.

PMID- 30190101
TI  - Sudden death in Parkinson's disease: Unjustifiably forgotten.
AB  - Parkinson's disease (PD) is one of the most common age-related neurodegenerative
      disorders. Epidemiological studies have demonstrated that PD is accompanied by
      high rates of premature death compared with the general population. The main
      causes of deaths are related to pneumonia and cardiovascular diseases.
      Importantly, it has also been recognized that some PD patients may eventually die
      unexpectedly and suddenly, referred as Sudden Unexpected Death in Parkinson's
      Disease (SUDPAR). Despite on-going PD research, there are still deficits in our
      knowledge about the risk factors, mechanisms and prevention of SUDPAR. By some
      means, current evidence suggests cardiac abnormalities and autonomic dysfunction
      plays an important role in SUDPAR. Thus, SUDPAR in patients with PD is a real
      phenomenon and translational studies should be carried out with the aim of
      elucidating this phenomenon.

PMID- 30190102
TI  - Everyday functioning in Parkinson's disease: Evidence from the Revised-Observed
      Tasks of Daily Living (OTDL-R).
AB  - INTRODUCTION: Performance tasks are presumed to have greater validity than rating
      scales in assessing day-to-day behaviors in Parkinson's disease (PD). One such
      task is the revised Observed Tasks of Daily Living (OTDL-R), which has been used
      extensively in healthy older adults, and but not yet empirically examined in PD.
      Thus, the aims of the current study were to examine and determine the impact of
      cognitive, motor, and mood symptoms on OTDL-R performance in PD. METHOD: Nineteen
      non-demented PD patients and 18 healthy older adults (HC) were administered
      measures of mood and cognitive functioning, and the OTDL-R (subtests include
      medication and telephone use, and medication management). Clinical severity of PD
      was assessed using the H&Y stage, UPDRS, and Schwab and England functional
      disability scores. RESULTS: Mann Whitney U tests indicated the PD patients were
      significantly slower to complete the OTDL-R and performed worse on only the
      telephone use subtest, relative to the HC group. In the PD group, hierarchical
      regression analyses revealed memory, attention, and initiative/perseveration were
      uniquely associated with the financial management subtest, after controlling for
      motor severity (ps < .05). No other significant relationships were found.
      CONCLUSIONS: PD patients were slower to complete the OTDL-R, but only less
      accurate on the telephone use subtest. Poor performance on the telephone use
      subtest may be related to motor severity, while poor performance on the financial
      management subtest was related to attention and working memory. Overall, the
      findings warrant future investigation to determine the validity and reliability
      of the OTDL-R in PD.

PMID- 30190103
TI  - Mycobacterium indicus pranii protein MIP_05962 induces Th1 cell mediated immune
      response in mice.
AB  - Utility of Mycobacterium indicus pranii (MIP) as a multistage vaccine against
      mycobacterial infections demands identification of its protective antigens. We
      explored antigenicity and immunogenicity of a candidate protein MIP_05962 that
      depicts homology to HSP18 of M. leprae and antigen1 of Mycobacterium
      tuberculosis. This protein elicited substantial antibody response in immunized
      mice along with modulation of cellular immune response towards protective Th1
      type. Both CD4+ and CD8+ subsets from immunized mice produced hallmark protective
      cytokines, IFN-gamma, TNF-alpha and IL-2. This protein also enhanced the CD4+
      effector memory that could act as first line of defence during infections. These
      results point to MIP_05962 as a protective antigen that contributes, in
      conjunction with others, to the protective immunity of this live vaccine
      candidate.

PMID- 30190104
TI  - Preface to the proceedings of the Workshop on Eosinophils in Allergy and Related
      Diseases 2017.

PMID- 30190105
TI  - Healthcare burden of recurrent Clostridioides difficile infection in Japan: A
      retrospective database study.
AB  - This retrospective database study aimed to assess the healthcare burden of
      hospitalization cost and duration associated with recurrent Clostridioides
      difficile infection (rCDI) by comparison with C. difficile infection (CDI) in
      Japan, using a health claims database of 270 acute care hospitals. Overall, 5423
      hospitalized patients, with a record of one hospital-onset, healthcare facility
      associated primary CDI episode within the 180-day period, from its onset between
      January 2012 and September 2016, were included. Of these, 353 had at least one
      rCDI and 5070 had no rCDI. Compared with those with no rCDI, the median total
      cost of hospitalization for patients with rCDI was JPY 1,184,371 (USD 11,691)
      higher (JPY 2,489,424 [interquartile range {IQR}: 1,597,424-4,008,751] compared
      with JPY 1,305,053 [624,033-2,549,569]). In addition, rCDI resulted in twice
      longer hospitalization duration in median compared with CDI (79 days [IQR: 53
      117] compared with 40 days [20-74]). Based on a generalized linear regression
      model with a Gamma distribution and a logarithmic link function, the estimated
      mean of cost and duration of hospitalization for patients with rCDI were JPY
      1,284,519 (95% confidence limit: -95,532-2,664,569) (USD 12,679) higher and 20.3
      days (-9.5-50.0) longer, compared with patients with no rCDI. The estimated mean
      difference in cost was higher in older patients and patients with diseases
      resulting in an immunosuppressive state. Higher costs and longer hospitalization
      for rCDI impose a great burden on healthcare system as well as patients,
      highlighting the importance of preventing recurrence of CDI.

PMID- 30190107
TI  - Enhancements to JAPhA.

PMID- 30190106
TI  - Surveillance of the prevalence of macrolide and/or fluoroquinolone resistance
      associated mutations in Mycoplasma genitalium in Japan.
AB  - To clarify the status of macrolide and fluoroquinolone resistance of clinical
      strains of Mycoplasma genitalium in Japan, we amplified portions of the gyrA,
      parC, and 23S rRNA genes from DNAs in 627 first-voided urine specimens collected
      from men with M. genitalium-positive urethritis who visited clinics mainly in
      Sendai, Tokyo, and Osaka, Japan, from 2013 to 2017, by PCR and sequenced. The
      incidence of single amino acid changes at Met95 or Asp99 in GyrA increased
      chronologically and was approximately 10% from 2015 onward. The incidence of
      amino acid changes at Ser83 or Asp87 in ParC was approximately 50% in 2013 but
      increased to 60-70% from 2014 to 2017. The incidence of mutations at A2071 or
      A2072 in the 23S rRNA gene increased chronologically and reached over 70% in
      2017. The prevalence of M. genitalium harboring alterations in ParC and mutations
      in the 23S rRNA gene increased and was approximately 50% in 2016 and 2017. The
      prevalence of M. genitalium with alterations in both GyrA and ParC and mutations
      in the 23S rRNA gene, which could be associated with treatment failures with the
      sitafloxacin and azithromycin regimens, were approximately 15% and 10% in 2016
      and 2017, respectively. The prevalence of M. genitalium with genetic alterations
      associated with resistance to fluoroquinolones and/or macrolides is increasing
      rapidly in Japan. We must prevent the further selection of multi-drug-resistant
      M. genitalium so that M. genitalium infections will not become untreatable.

PMID- 30190108
TI  - Mumps outbreaks: Implementation of a third dose of mumps-containing vaccine.

PMID- 30190109
TI  - Erenumab-aooe, Benralizumab, and Tezacaftor/ivacaftor.

PMID- 30190110
TI  - Extended versus conventional thromboprophylaxis after major abdominal and pelvic
      surgery: Systematic review and meta-analysis of randomized clinical trials.
AB  - BACKGROUND: Venous thromboembolism, presenting as deep vein thrombosis or
      pulmonary embolism, can be associated with considerable morbidity after major
      abdominal and pelvic surgery. Perioperative thromboprophylaxis with low-molecular
      weight heparin is well established, but the duration of treatment remains
      debated. We aimed to assess the efficacy and safety of extended (4-week) versus
      conventional (1-week) thromboprophylaxis with low-molecular-weight heparin in
      patients undergoing abdominopelvic surgery. METHODS: Using MEDLINE databases
      (PubMed, EMBASE, and Web of Science), we conducted an electronic, systematic
      search of randomized controlled trials comparing post-operative extended versus
      conventional low-molecular-weight heparin on venous thromboembolism, deep vein
      thrombosis, and pulmonary embolism rates. RESULTS: Four randomized controlled
      trials met the predefined criteria. Extended prophylaxis with low-molecular
      weight heparin after major abdominal and pelvic surgery decreased rates of
      postoperative venous thromboembolism, deep vein thrombosis, and proximal deep
      vein thrombosis without increased postoperative bleeding. Numbers needed to treat
      to prevent venous thromboembolism, overall deep vein thrombosis, and proximal
      deep vein thrombosis were 14, 14, and 44, respectively. Rates of postoperative
      symptomatic PE were rare, and the incidence was similar in both groups.
      CONCLUSION: Extended prophylaxis with low-molecular-weight heparin is associated
      with a decrease in asymptomatic venous thromboembolism. There remains sparse
      evidence regarding its impact on pulmonary embolism because of the overall low
      incidence. Extended prophylaxis should be considered in high-risk patients.

PMID- 30190111
TI  - Systematic Review on the Utilization of Maintenance Intravesical Chemotherapy in
      the Management of Non-muscle-invasive Bladder Cancer.
AB  - CONTEXT: Current guidelines remain ill-defined regarding the optimal intravesical
      chemotherapy type and regimen for the treatment of non-muscle-invasive bladder
      cancer (NMIBC). Although maintenance therapy is a standard part of bacillus
      Calmette-Guerin (BCG) therapy, its role in the context of chemotherapy remains
      debatable. OBJECTIVE: We reviewed the literature regarding the utilization of
      intravesical maintenance chemotherapy in the treatment of NMIBC to determine its
      impact on recurrence, progression, and survival. EVIDENCE ACQUISITION: A
      systematic search was conducted using Ovid and Medline according to the Preferred
      Reporting Items for Systematic Reviews and Meta-analyses guidelines to identify
      studies between 1970 and 2018 reporting on the utilization of maintenance
      intravesical chemotherapy. Only randomized controlled trials (RCTs) that included
      a comparison between an induction regimen and an induction plus maintenance
      regimen were included. EVIDENCE SYNTHESIS: Sixteen RCTs were included in the
      final analysis. The most commonly studied intravesical chemotherapy agents used
      in maintenance regimens were epirubicin, doxorubicin, and mitomycin C. Several
      maintenance schedules were utilized, some as short as 3mo and others as long as 3
      yr, while the most common maintenance regimen utilized was monthly instillation
      for 1 yr. Of the 16 trials, 13 reported no significant improvement in recurrence
      for patients receiving maintenance compared with no maintenance, and none of the
      trials demonstrated a significant impact on progression or survival. CONCLUSIONS:
      Intermediate length maintenance regimens lasting 7-12mo were the most common
      maintenance regimens utilized. There was considerable heterogeneity between trial
      design and duration of follow-up, making direct comparisons for recurrence,
      progression, and survival outcomes between trials challenging. Although
      maintenance intravesical chemotherapy is suggested as a treatment option for
      patients with NMIBC by some guidelines, the majority of evidence suggested that
      it provided no significant advantage over induction therapy alone with respect to
      recurrence, progression, or survival. PATIENT SUMMARY: In this review, we
      reviewed prior clinical trials to determine whether prolonged intravesical
      chemotherapy ("maintenance therapy") improved the rates of recurrence,
      progression, and survival. Where differences were found in favor of maintenance
      therapy, there was no statistical significance demonstrated, possibly due to the
      underpowered nature of the study design. While there was no consensus on an
      optimal agent or maintenance schedule, we found no evidence to suggest that
      maintenance therapy would improve recurrence, progression, or survival.

PMID- 30190112
TI  - The value of incorporating medical nutrition therapy by a registered dietitian
      nutritionist in clinical practice.

PMID- 30190113
TI  - Determinants and prognostic implication of diagnostic delay in patients with a
      first episode of pulmonary embolism.
AB  - Signs and symptoms of pulmonary embolism (PE) are not specific and this can lead
      to a diagnostic delay. Little is known about the determinants of this delay and
      its prognostic implication. We conducted a retrospective analysis of a
      prospective cohort involving 514 patients with a first episode of PE. The
      diagnostic delay was defined as a time from first symptom onset to diagnosis of
      >3 days, corresponding of the median time in the population. Multivariable
      logistic regression analysis was performed to identify determinants of diagnostic
      delay. Prognostic implication was measured as the occurrence of 30-day all-cause
      mortality, haemodynamic collapse or recurrent PE. A total of 240 (47%) among 514
      patients had a time from first symptom to diagnosis > 3 days. Previous deep vein
      thrombosis (OR 0.55, 95% Confidence Interval (CI), 0.32-0.93), immobilization (OR
      0.52, 95% CI, 0.28-0.96), surgery (OR 0.31, 95% CI, 0.16-0.62), chest pain (OR
      0.58, 95% CI, 0.39-0.86), syncope (OR 0.48, 95% CI, 0.23-1.01), dyspnea (OR 2.48,
      95% CI, 1.57-3.91) and hemoptysis (OR 3.57, 95% CI, 1.40-9.07) were associated
      with diagnostic delay. Twenty-two patients (4.3%, 95%CI, 2.8-6.5) experienced an
      outcome event within 30 days. Among them, 15 patients (6.2% 95%CI, 3.7-10.3) had
      a diagnostic delay and 7 (2.6%, 95% CI 1.1-5.4) did not (p = 0.039). In this
      cohort, diagnostic delay is associated with the absence of major risk factors for
      PE or clinical features such as chest pain or syncope and the presence of dyspnea
      or hemoptysis. Diagnostic delay is associated with a worse 30-day prognosis.

PMID- 30190115
TI  - Toxicology of Explosives and Fireworks in Small Animals.
AB  - Exposure to explosives and fireworks in dogs can result in variable severity of
      clinical signs depending on the presence of different chemicals and the amount.
      The risk can be lessened by proper education of dog handlers and owners about the
      seriousness of the intoxications. Most animals will recover within 24 to 72 hours
      with supportive care. Cyclonite, barium, and chlorate ingestion carries a risk of
      more severe clinical signs.

PMID- 30190116
TI  - Corrigendum to "Implications on the Pb bioaccumulation and metallothionein levels
      due to dietary and waterborne exposures: The Callinectes danae case" [Ecotoxicol.
      Environ. Saf. 2018 415-422].

PMID- 30190117
TI  - Association between the dietary inflammatory index and common mental health
      disorders profile scores.
AB  - BACKGROUND & AIMS: The association between diet and mental health disorders might
      be mediated by inflammatory properties of the diet. We evaluated the association
      between the dietary inflammatory index (DII) and the risk of a worsened mental
      health disorders profile. METHODS: A total of 3363 Iranian adults were included
      in this cross-sectional study. A mental health disorders profile score was
      calculated using regression analysis, within the framework of factor analysis,
      based on anxiety, depression and psychological distress, with a higher scores
      indicating greater severity of mental problems. Dietary intakes were assessed
      using a validated dish-based food frequency questionnaire (DFQ). Twenty-seven
      macro- and micro-nutrients, onions, tea and caffeine were included in the
      calculation of DII. Each of them received a score based on their inflammatory
      ability, thus, a greater DII indicated a more pro-inflammatory diet. The odds of
      being in the highest tertile of mental health disorders profile across the
      tertiles of DII was assessed using multinomial logistic regression. RESULTS:
      Either in the crude or fully-adjusted multinomial logistic regression models,
      participants in the lowest tertile of DII had a lower risk for being in the top
      tertile of mental health disorders profile (adjusted model: OR: 0.45; 95% CI:
      0.33, 0.60; P trend<0.001). In a stratified analysis by sex, similar findings
      were observed in both genders, although there was only a trend for the
      associations to be significant in men (men: OR: 0.53; 95% CI: 0.31, 0.90; P trend
      = 0.070; women: OR: 0.40; 95% CI: 0.27, 0.58; P trend<0.0001). CONCLUSIONS: Our
      findings suggest a direct association between the pro-inflammatory properties of
      the diet and an increased risk of higher mental health disorders profile scores.
      Prospective dietary intervention studies and observational prospective cohorts
      are required to confirm these findings.

PMID- 30190114
TI  - SQ1274, a novel microtubule inhibitor, inhibits ovarian and uterine cancer cell
      growth.
AB  - OBJECTIVE: Paclitaxel, a microtubule inhibitor, is subject to tumor resistance
      while treating high-grade serous ovarian and uterine cancer. This study aims to
      directly compare the effects of SQ1274, a novel microtubule inhibitor that binds
      to the colchicine-binding site on tubulin, and paclitaxel in high-grade serous
      ovarian and uterine cancer cell lines both in vitro and in vivo. METHODS: We
      assessed the sensitivity of ovarian (OVCAR8) and uterine (ARK1) cancer cell lines
      to SQ1274 and paclitaxel using XTT assays. We used western blot and quantitative
      real-time PCR to analyze changes in AXL RNA and protein expression by SQ1274 and
      paclitaxel. Differences in cell-cycle arrest and apoptosis were investigated
      using flow cytometry. Finally, we treated ovarian and uterine xenograft models
      with vehicle, paclitaxel, or SQ1274. RESULTS: First, we demonstrate that SQ1274
      has a much lower IC50 than paclitaxel in both ARK1 (1.26 nM vs. 15.34 nM,
      respectively) and OVCAR8 (1.34 nM vs. 10.29 nM, respectively) cancer cell lines.
      Second, we show SQ1274 decreases both RNA and protein expression of AXL. Third,
      we show that SQ1274 causes increased cell-cycle arrest and apoptosis compared to
      paclitaxel. Finally, we report that SQ1274 more effectively inhibits tumor growth
      in vivo compared to paclitaxel. CONCLUSIONS: SQ1274 presents as a viable
      alternative to paclitaxel for treating ovarian and uterine cancer. This study
      supports the development of SQ1274 as a chemotherapeutic to treat ovarian and
      uterine cancer.

PMID- 30190118
TI  - Extra-skeletal impact of vitamin D supplementation protocol in an adult
      population with cystic fibrosis.
AB  - BACKGROUND: Due to lack of vitamin D absorption in patients with cystic fibrosis
      (CF), vitamin D supplementation becomes necessary. Our aim was to study the
      association between serum vitamin D levels and key clinical factors, such as
      nutritional status, pulmonary function and pulmonary exacerbations (PEx)
      frequency, in an adult CF population. METHODS: Prospective analysis of a
      published vitamin D (VitD3) supplementation protocol (N = 200 adult patients)
      over a follow-up period of 5 years. Data were collected from the medical files
      before (baseline) and after (follow-up) the implementation of the VitD3
      supplementation protocol, between 2009 and 2014. Serum samples to measure vitamin
      D were also collected at baseline and follow-up. RESULTS: A positive relationship
      between serum vitamin D and lung function was observed at baseline (R = 0.158, P
      = 0.027), but it disappeared at follow-up (P = 0.454). There was no association
      between serum vitamin D levels and body mass index. At follow-up, patients with
      significantly higher serum vitamin D levels were women, older in age, had CF
      related diabetes or had a history of recurring PEx. CONCLUSION: No direct link
      was observed between heightened serum vitamin D and lung function or BMI in an
      adult CF population. We suggest that better compliance to treatments and closer
      follow-up from health professionals could partially explain why such patients
      reached higher vitamin D serum levels.

PMID- 30190119
TI  - Safety profile of fractional dosing of the 17DD Yellow Fever Vaccine among males
      and females: Experience of a community-based pharmacovigilance in Kinshasa, DR
      Congo.
AB  - BACKGROUND: In early 2016, there was a Yellow Fever (YF) outbreak in Central
      Africa with several deaths reported from Angola and the Democratic Republic of
      Congo. Due to a shortage in vaccine supply, fractional dosing (0.1 ml) of 17DD
      Yellow Fever Vaccine (YFV) was proposed in preventive vaccination campaign in
      Kinshasa in August 2016. A Pharmacovigilance surveillance at community level was
      implemented to track Adverse Events Following Immunization (AEFIs). The objective
      of this study was to describe AEFIs as captured from community-based
      pharmacovigilance and to compare the safety profile of the fractional dosing of
      YFV between gender. METHODS: PV information sessions were organized in churches,
      academic institutions, and pediatrician, obstetrician and friend networks. Prior
      to data collection, education about AEFI was provided through face-to-face
      discussions, phone calls, SMS and WhatsApp messages. Individuals reported AEFIs
      though the above communication channels to assigned individuals. Reported AEFIs
      were entered into VigiFlow and extracted for statistical analysis using Stata 12.
      Only vaccinees who received fractional dose (subjects from the age of 2-year-old
      and non-pregnant women) were included in analysis. Proportional t-test was used
      to compare AEFI preferred terms among males and females. RESULTS: A total of 4020
      subjects reported 5409 AEFIs. Reporters were mostly males (54.9%) with an average
      age of 26 +/- 10.7 years. Fever and injection site pain were the most reported
      systemic and local AEFI respectively. The safety profile was similar between
      gender although females reported more diarrhea and dizziness whilst males
      reported more asthenia (P < 0.001). Five individuals reported serious AEFIs.
      Among them, 4 were less-immunocompetent. CONCLUSION: Fractional dosing of 17DD
      YFV has a good safety profile, which is similar between gender. These findings
      complement the documented immunogenicity profile to support recommendation of
      fractional dose of YFV for outbreak control.

PMID- 30190120
TI  - Replication deficient human adenovirus vector serotype 19a/64: Immunogenicity in
      mice and female cynomolgus macaques.
AB  - The human adenovirus type 19a/64 (hAd19a) is a rare serotype in the human
      population that transduces human dendritic cells (DCs) and human muscle cells
      more efficiently than the well-characterized human adenovirus type 5 (hAd5). To
      further characterize the potential of this vector as a vaccine we designed
      replication deficient hAd19a, hAd5 and MVA vectors expressing a papillomavirus
      (PV) antigen fused to the human MHC class II associated invariant chain T cell
      adjuvant (hIi) and investigated their immunogenicity in vivo in mice and
      cynomolgus macaques. We initially showed that the hIi encoded in the hAd5
      enhanced PV specific CD8+ T cell responses in mice. The T cell responses induced
      after hAd19a vaccination was similar to those induced by hAd5 vaccination. The
      hAd19a induced responses were not reduced in presence of preexisting Ad5 immunity
      in mice. In macaques both vaccines were equally potent at inducing CD8+ T cells
      after MVA boost, while the level of CD4+ T cell responses were found to be
      broader in hAd19a primed animals. These data demonstrate the potential of hAd19a
      as an alternative vector to hAd5 to elicit potent T cell responses to PV.

PMID- 30190121
TI  - The effectiveness of influenza vaccination against medically-attended illnesses
      in Hong Kong across three years with different degrees of vaccine match, 2014-17.
AB  - BACKGROUND: Influenza vaccination is the most effective intervention to prevent
      influenza virus infections. Vaccine effectiveness (VE) can vary due to factors
      such as matching between vaccine strains and prevailing strains, age and other
      characteristics of the vaccine recipients. OBJECTIVE: To evaluate influenza VE
      against medically-attended illness in different age groups and against specific
      influenza types/subtypes in Hong Kong. METHODS: A test-negative study was
      conducted from December 2014 through August 2017 in 20 outpatient clinics.
      Patients at least 6 months of age presenting with at least two symptoms of acute
      respiratory illness, ARI (fever >=37.8  degrees C, cough, sore throat, runny
      nose, headache, myalgia and phlegm) within 72 h of onset were tested for
      influenza virus by reverse transcription polymerase chain reaction (PCR).
      Vaccination history was assessed by self-report or medical records at the
      clinics. VE against medically-attended illness was estimated using conditional
      logistic regression for influenza PCR result versus vaccination history, matching
      by calendar time and adjusting for age, age-squared, sex, and chronic medical
      illness. Additional analyses examined VE by age group and by influenza
      type/subtype. RESULTS: We enrolled 2566 patients, of whom 1118 (43.6%) tested
      positive for influenza A or B virus by PCR. Test-positive subjects were generally
      older, more likely to present with one of the symptoms of ARI, and less likely to
      receive vaccination against influenza. VE estimates for influenza A(H1N1),
      A(H3N2), B/Yamagata and B/Victoria were 61.6% (95% confidence interval, CI:
      21.8%, 81.1%), 26.4% (95% CI: -1.3%, 46.6%), 67.0% (95% CI: 25.9%, 85.3%), 60.4%
      (95% CI: 0.3%, 84.3%), respectively. Estimates of VE by age group were generally
      higher in adults aged 50-64 and lower among children and older adults.
      CONCLUSIONS: VE against medically-attended influenza was moderate in Hong Kong,
      confirming the impact of influenza vaccination in reducing disease burden. The
      reduced VE for influenza A(H3N2) is a continuing concern.

PMID- 30190122
TI  - Ectopic vascularized bone formation by human umbilical cord-derived mesenchymal
      stromal cells expressing bone morphogenetic factor-2 and endothelial cells.
AB  - Mesenchymal stromal cells (MSCs) isolated from numerous tissues including human
      fetal tissue are currently used in cell therapy and regenerative medicine. Among
      fetal tissues, the umbilical cord (UC) is one of the sources for both MSCs and
      endothelial cells (ECs). To establish ectopic vascularized bone tissue formation,
      UC-derived MSCs and ECs were isolated. UC-MSCs expressing human BMP-2 (hBMP-2
      MSCs) were generated using an adenoviral system to promote bone formation. These
      cells were then transplanted with Matrigel into the subcutaneous tissue of an
      immune deficient NSG mouse, and bone tissue was analyzed after several weeks. The
      osteogenic differentiation ability of MSCs was elevated by transduction of the
      hBMP-2 expressing adenoviral system, and vascularization of bone tissue was
      enhanced by human umbilical vein endothelial cells (HUVEC). In this study, our
      results provide evidence that MSCs and HUVECs from human umbilical cord are
      suitable cells to investigate bone tissue engineering. The results also suggest
      that the co-transplantation of hBMP2-MSCs and HUVECs may be a simple and
      efficient strategy for improving tissue generation and angiogenesis in bone
      tissue engineering using stem cells.

PMID- 30190123
TI  - Berberine derivative, Q8, stimulates osteogenic differentiation.
AB  - Berberine has been implicated to be involved in maintaining bone health due to
      its anti-oxidative and osteogenic properties. However, low potency and low
      bioavailability limit the clinical development of the drug. To overcome these
      obstacles, we previously synthesized a compound, Q8, which is a structural
      homolog of berberine. The present study examined the pharmacological functions of
      Q8 to evaluate its potential use in bone regeneration with respect to osteoblast
      differentiation. Here, we report that Q8 enhanced BMP4-induced alkaline
      phosphatase (ALP) activity and transcription from the ALP promoter. In addition,
      Q8 suppressed the expression and activity of PPARgamma (a known negative
      regulator of osteogenesis due to its stimulatory effects on adipogenesis and its
      role as an adipogenic transcription factor), which in turn increases beta-catenin
      expression in the nucleus, and ultimately promotes osteoblast differentiation.
      Meanwhile, Q8 reversed the inhibitory effects of the PPARgamma agonist,
      rosiglitazone, on osteoblast differentiation. This study demonstrated that Q8
      promotes osteoblast differentiation via inhibition of PPARgamma and the
      enhancement of osteoblast function by Q8 may contribute to the prevention for
      osteoporosis.

PMID- 30190124
TI  - MiR-590-5p alleviates intracerebral hemorrhage-induced brain injury through
      targeting Peli1 gene expression.
AB  - Intracerebral haemorrhage (ICH) is a common and devastating cerebrovascular
      disease with high morbidity and mortality, and its pathophysiological mechanisms
      were complex and still unclear. Increasing researches reported that microRNAs
      (miRNAs) played an important role in ICH-induced brain injury and microglial
      activation. In this study, we investigated the biological function of miR-590-5p
      and explored its molecular mechanism in ICH mice. The results of qRT-PCR showed
      that miR-590-5p expression level was down-regulated in perihematomal brain
      samples of ICH mice compared with that of sham group. In LPS-induced microglia
      cells, miR-590-5p level was also down-regulated at 24 h post-LPS compared with
      that of control group. Moreover, miR-590-5p overexpression remarkably increased
      the cerebral water content and neurological severity scores compared with that of
      scramble group in ICH mice. The production of inflammatory cytokine including IL
      6, interleukin (IL)-1beta, and tumor necrosis factor (TNF)-alpha in ICH mice was
      notably inhibited by miR-590-5p overexpression. Furthermore, the results of dual
      luciferase reporter assay indicated that Pellino-1 (Peli1) was a direct target of
      miR-590-5p. MiR-590-5p overexpression remarkably inhibited the Peli1 gene
      expression both mRNA and protein levels. In addition, Peli1 overexpression partly
      abrogated the inhibitory effect of miR-590-5p mimic. Taken together, these datas
      suggested that miR-590-5p attenuated brain injury in ICH mice through inhibiting
      Peli1 gene expression, indicating that miR-590-5p may be a promising molecular
      target for ICH treatment.

PMID- 30190125
TI  - Autoimmune sialadenitis is associated with the upregulation of
      chemokine/chemokine receptor pairs in T cell-specific TRAF6-deficient mice.
AB  - Sialadenitis is an inflammatory condition affecting the salivary glands including
      the parotid, submandibular, and sublingual glands. There are several different
      types of sialadenitis, each with different sites of predilection. However, the
      pathogenic mechanism underlying the tissue specificity of sialadenitis is largely
      unknown. TRAF6 is a cytoplasmic adaptor protein that is necessary for the
      activation of dendritic cells in response to Toll-like receptor ligands, thereby
      regulating innate immune responses. We previously demonstrated that T cell
      specific TRAF6-deficient mice (TRAF6DeltaT mice) spontaneously develop systemic
      inflammatory disease. Here, we show that salivary secretion is reduced in
      TRAF6DeltaT mice due to sialadenitis that occurs in the parotid and submandibular
      glands, but not the sublingual glands. Consistent with pathological findings,
      both CD4+ and CD8+ T cells predominantly infiltrated the submandibular glands;
      however, sublingual infiltration was rare in TRAF6DeltaT mice. The TH1 cytokine
      IFN-gamma, the TH1 cell attractant chemokine CCL2, and its cognate receptor CCR2
      were upregulated concomitantly in both the submandibular and sublingual glands.
      Interestingly, the TH17 cell attractant chemokine CCL20 and its cognate receptor
      CCR6 were selectively increased in the submandibular glands, but not in the
      sublingual glands of TRAF6DeltaT mice. Thus, the expression of TRAF6 in T cells
      might be implicated in tissue-specific sialadenitis by regulating the chemokine
      chemokine receptor system.

PMID- 30190126
TI  - SPOP promotes FADD degradation and inhibits NF-kappaB activity in non-small cell
      lung cancer.
AB  - FAS-associated protein with death domain (FADD) is the pivotal adaptor protein,
      which transmits apoptotic signals mediated by the death receptors. Here we report
      that high FADD protein level predicts poor prognosis of non-small cell lung
      cancer (NSCLC) patients and its protein level is mainly regulated by the 26S
      proteasome. We also found that ubiquitin ligase SPOP (speckle-type POZ protein)
      binds to FADD and mediates its degradation, which can be blocked by MG132
      treatment. Notably, SPOP inhibits NF-kappaB (nuclear factor kappa-light-chain
      enhancer of activated B cells) activity and its target genes expression via FADD.
      These results reveal the function of SPOP-FADDNFkappaB axis in NSCLC cells, which
      is associated with prognosis of NSCLC patients.

PMID- 30190127
TI  - Association of NPSR1 rs324981 polymorphism and treatment response to
      antidepressants in Chinese Han population with generalized anxiety disorder.
AB  - In previous studies, neuropeptide S (NPS) and its cognate receptor (NPSR) have
      been involved in the pathogenesis of anxiety disorders in previous studies. Here,
      we aimed to investigate the association of NPSR1 polymorphism with generalized
      anxiety disorder (GAD) and its treatment response in Chinese Han population.
      Three hundred and thirty seven patients and one hundred and seventy seven healthy
      controls were involved in our study for 8 weeks. Further, Hamilton Anxiety Scale
      (HAMA) was used to assess anxiety symptom at baseline and the 1st, 2nd, 4th, 8th
      week. And all participants were genotyped for NPSR1 (rs324981) variants by
      polymerase chain reaction. Using Repeated-measures analysis, it showed
      significant reduction on HAMA scores in patients treated with escitalopram (F =
      1.03, P = 0.362) and venlafaxine (F = 0.27, P = 0.763) respectively through 8
      weeks treatment. Additionally, patients with AA and TT homozygous genotypes
      treated with venlafaxine XR had a higher reduction of HAMA scores compared to AT
      heterozygotic carriers (F = 4.18, P = 0.004), while no significant differences
      were found in patients treated with escitalopram (F = 1.05, P = 0.383). Thus, our
      study provides preliminary evidence that NPSR1 AA and TT homozygous genotypes
      have better treatment responses to venlafaxine XR in Chinese GAD patients, but
      not to escitalopram. Further studies are needed to verify the observation.

PMID- 30190128
TI  - Crystal structure of Escherichia coli DEAH/RHA helicase HrpB.
AB  - RNA helicases are almost ubiquitous important enzymes that take part in multiple
      aspects of RNA metabolism. Prokaryotes encode fewer RNA helicases than
      eukaryotes, suggesting that individual prokaryotic RNA helicases may take on
      multiple roles. The specific functions and molecular mechanisms of bacterial
      DEAH/RHA helicases are poorly understood, and no structures are available of
      these bacterial enzymes. Here, we report the first crystal structure of the
      DEAH/RHA helicase HrpB of Escherichia coli in a complex with ADP*AlF4. It showed
      an atypical globular structure, consisting of two RecA domains, an HA2 domain and
      an OB domain, similar to eukaryotic DEAH/RHA helicases. Notably, it showed a
      unique C-terminal extension that has never been reported before. Activity assays
      indicated that EcHrpB binds RNA but not DNA, and does not exhibit unwinding
      activity in vitro. Thus, within cells, the EcHrpB may function in helicase
      activity-independent RNA metabolic processes.

PMID- 30190130
TI  - CircRNA circ-ITCH suppresses papillary thyroid cancer progression through miR-22
      3p/CBL/beta-catenin pathway.
AB  - While recent evidence has uncovered that circular RNAs (circRNAs) are vital
      regulators of carcinogenesis, their role in papillary thyroid cancer (PTC) is not
      clearly understood. In this study, we reveal that lower levels of circRNA circ
      ITCH are expressed in PTC tissues than in normal adjacent tissues. Gain-of
      functional assays show that circ-ITCH overexpression suppresses PTC cell
      proliferation and invasion and promotes apoptosis in vitro. Overexpression of
      circ-ITCH also leads to impaired tumor growth in vivo. Bioinformatics analysis
      and luciferase reporter assays demonstrate that circ-ITCH sponges miR-22-3p to
      upregulate the expression of CBL, an E3 ligase of nuclear beta-catenin. Elevated
      levels of CBL suppress activation of the Wnt/beta-catenin pathway and
      consequently attenuates PTC progression. In summary, our study reveals a novel
      signaling pathway of circ-ITCH/miR-22-3p/CBL/beta-catenin involved in PTC
      development and progression.

PMID- 30190129
TI  - A transient post-translational modification of active site cysteine alters
      binding properties of the parkinsonism protein DJ-1.
AB  - Mutations in the human protein DJ-1 cause early onset of Parkinson's disease. A
      reactive cysteine residue (Cys106) of DJ-1 is crucial for its protective
      function, although the underlying mechanisms are unclear. Here we show that a
      fraction of bacterially expressed polyhistidine-tagged human DJ-1 could not be
      eluted from a Ni-nitrilotriacetate (Ni-NTA) column with 150 mM imidazole. This
      unusually tight binding was accompanied by the appearance of blue violet color on
      the Ni-NTA column. We demonstrate by X-ray crystallography that Cys106 is
      carboxymethylated in a fraction of DJ-1 tightly bound to Ni-NTA and that the
      replacement of Cys106 by serine abrogates the tight binding and the appearance of
      blue violet color. However, carboxymethylation of purified DJ-1 is insufficient
      to confer the tight binding to Ni-NTA. Moreover, when eluted protein was re
      applied to the Ni-NTA column, no tight binding was observed, indicating that the
      formation of high affinity complex with Ni-NTA depends on a transient
      modification of Cys106 that transforms into a Cys106-carboxymethyl adduct upon
      elution from Ni-NTA. We conclude that an unknown metabolite reacts with Cys106 of
      DJ-1 to result in a transient post-translational modification. This modification
      is distinct from simple oxidation to sulfinic or sulfenic acids and confers
      altered binding properties to DJ-1 suggesting that it could serve as a signal for
      sensing oxidant stress.

PMID- 30190131
TI  - Sanguisorba officinalis L. extracts activate Wnt/beta-catenin pathway, and
      subsequently control adipo-osteogenic differentiation.
AB  - Wnt/beta-catenin pathway plays an important role in adipogenesis and
      osteogenesis. To search for novel activators of the Wnt/beta-catenin pathway, we
      screened plant extracts and found that Sangusorba officinalis L. extracts (SOE)
      could increase beta-catenin expression level and nuclear accumulation in 3T3-L1
      and MC3T3-E1 cells. It was confirmed that SOE could effectively control adipo
      osteogenic differentiation. SOE inhibited adipocyte differentiation of 3T3-L1
      cells, markedly decreased intracellular lipid accumulation, and decreased
      expression levels of key adipogenic transcription factors including PPARgamma,
      C/EBPalpha, and SREBP-1c. SOE enhanced ALP activity and terminal osteoblast
      differentiation which was confirmed by Alizarin Red S staining of MC3T3-E1 cells.
      In ex vivo culture, SOE significantly increased the thickness of calvarial bone
      in mice. Taken together, our results indicate that SOE could be used as a
      potential therapeutic agent for dual-treatment of anti-obesity and anti
      osteoporosis via activation of Wnt/beta-catenin pathway.

PMID- 30190132
TI  - OsCML16 interacts with a novel CC-NBS-LRR protein OsPi304 in the Ca2+/Mg2+
      dependent and independent manner in rice.
AB  - In plants, many target proteins of calmodulins (CaMs) have been identified in
      cellular metabolism and responses. However, calmodulin-like proteins (CMLs) and
      their target proteins have not been discovered in stress responses in rice. In
      this study, a novel CC-NBS-LRR protein was obtained in screening a cold stress
      rice seedlings yeast cDNA library with OsCML16 as bait. Furthermore, yeast two
      hybrid and BiFC assays demonstrated that the full length, CC region in the N
      terminus and LRR in the C-terminus of Pi304 protein could interact with OsCML16.
      More interestingly, OsCML16 bound to the 1-10 motif rather than 1-14 motif in the
      Ca2+ or Mg2+ dependent manner in vitro. In addition, transcript levels of OsCML16
      and OsPi304 were induced more markedly in Nipponbare than in 9311 under cold
      stress. Taken together, these data indicates that they are involved in the cold
      stress signaling and response in rice.

PMID- 30190133
TI  - The ADP-ribose reactive NUDIX hydrolase isoforms can modulate HIF-1alpha in
      cancer cells.
AB  - The human nucleoside-diphosphate linked moiety-X (NUDIX) hydrolases that utilize
      ADP-ribose and NADH/NAD+ are overexpressed in cancer cells, but their roles in
      hypoxia inducible factor-1alpha (HIF-1alpha) regulation have not yet been
      revealed. Here, we showed that these NUDIX hydrolases negatively regulated HIF
      1alpha accumulation by modulating the Ca2+ dependent AMP-activated protein kinase
      (AMPK) signaling pathway. In specific, knockdown of NUDT9 resulted in
      accumulation of free ADP-ribose that triggered Ca2+ influx mediated by transient
      receptor potential cation channel subfamily M member 2 and subsequent activation
      of Ca2+/calmodulin-dependent protein kinase kinase beta (CaMKKbeta). In addition,
      AMPK activation by CaMKKbeta was shown to enhance HIF-1alpha accumulation. Our
      findings provide insights into the action of NUDIX hydrolases as an additional,
      discrete modulator of HIF-1alpha accumulation.

PMID- 30190134
TI  - Observation of ultrasonic Talbot effect in perforated plates.
AB  - The Talbot effect using ultrasonic waves transmitted through a periodic
      perforated plate is presented. The ultrasonic wave-field at the exit of the
      perforated plate replicates the perforated pattern at the Talbot distance.
      Experimental results are validated by an analytical model. The measured
      propagating wave-field is consistent with the analytical results. The influence
      of the grating size and the filling fraction on the Talbot effect are also
      studied, and it is found that both parameters affect the formation of Talbot
      images.

PMID- 30190135
TI  - Updates in Thyroid Cytology.
AB  - Genomic, clinical, and pathologic studies have prompted a more risk-stratified
      approach to the management of patients with thyroid nodules. The recent
      nomenclature change concerning noninvasive follicular thyroid neoplasm with
      papillary-like nuclear features reflects the clinical trend toward conservative
      treatment choices for carefully selected low-risk thyroid neoplasms. These
      developments have occurred in parallel with a growing array of molecular tests
      intended to improve clinical triage for patients with indeterminate fine needle
      aspiration diagnoses. This review discusses the implications of the nomenclature
      revision on the interpretation of thyroid fine needle aspiration and updates
      available ancillary molecular tests for thyroid fine needle aspirations.

PMID- 30190136
TI  - Updates in Salivary Gland Fine Needle Aspiration Biopsy: The Use of the Milan
      System and Ancillary Testing.
AB  - Salivary gland fine needle aspiration biopsies remain common specimens seen by
      most cytology services. The diagnostic diversity and overlap between many of the
      lesions seen with these biopsies impart many challenges for the cytopathologist,
      rendering most specific diagnoses impossible with cytology alone. Here, the use
      of the Milan System for the classification of salivary gland fine needle
      aspiration biopsy FNAB is discussed, together with the potential use of ancillary
      testing in arriving at definitive diagnoses.

PMID- 30190137
TI  - Head and Neck Cytopathology: Human Papillomavirus-Positive Carcinomas, Including
      Diagnostic Updates, Testing Modalities, and Recommendations.
AB  - Oropharyngeal squamous cell carcinoma caused by transcriptionally active human
      papillomavirus (HPV) is now well established as a unique form of head and neck
      cancer. Given the high frequency of metastasis to cervical lymph nodes by HPV
      positive oropharyngeal squamous cell carcinomas, fine-needle aspiration (FNA)
      represents a widely accepted method for the sampling and diagnosis of these
      cancers. The recently published College of American Pathologists Guideline (2017)
      provides recommendations for the effective performance and interpretation of high
      risk (HR) HPV testing in head and neck squamous cell carcinoma (HNSCC), including
      testing on FNA samples of metastatic HNSCC to cervical lymph nodes. There is a
      wide range of options available for HR-HPV testing in cytologic specimens.

PMID- 30190139
TI  - Updates in Effusion Cytology.
AB  - Effusion cytology plays multiple roles in the management of benign and malignant
      disease, from primary diagnosis to tissue allocation for ancillary diagnostic
      studies and biomarker testing of therapeutic targets. This article summarizes
      recent advances in pleural effusion cytology, with a focus on the practical
      application of immunohistochemical markers, cytogenetic techniques, flow
      cytometry, and molecular techniques for the diagnosis and management of primary
      and secondary neoplasms of the pleura.

PMID- 30190138
TI  - Updates in Lung Cancer Cytopathology.
AB  - Lung cancer diagnosis and ancillary testing are increasingly relying on cytology
      and small biopsy specimens obtained via minimally invasive means. Paired with
      traditional immunohistochemical characterization of tumors, biomarker testing and
      comprehensive genomic profiling are becoming essential steps in the workup of
      lung cancer to identify targetable alterations and guide optimal therapy
      selection. Recent advances in immune checkpoint inhibitor therapy have led to an
      increasingly complex and unresolved landscape for tumor PD-L1 testing. The
      prevalence and importance of lung cancer cytology specimens are growing, with
      more required by the cytopathologist in directing the care of patients with lung
      cancer.

PMID- 30190140
TI  - Evaluation of Carcinoma of Unknown Primary on Cytologic Specimens.
AB  - Carcinoma of unknown primary is defined as metastatic carcinoma without a
      clinically obvious primary tumor. Determining the tissue of origin in carcinoma
      of unknown primary is important for site-directed therapy. Immunohistochemistry
      is the most widely used tool for the work-up of metastases, but molecular
      profiling assays are also available. This review provides an overview of
      immunohistochemical stains in the work-up of metastatic carcinoma, with a focus
      on newer site-specific markers, and discusses the role of gene expression
      profiling assays for determining tissue of origin. The utility of cytopathology
      specimens in the evaluation of carcinoma of unknown primary also is highlighted.

PMID- 30190141
TI  - Pancreatic Cytology.
AB  - The diagnostic approach to pancreaticobiliary disease requires a
      multidisciplinary team in which the cytopathologist plays a crucial role. Fine
      needle aspiration, obtained by endoscopic ultrasound, is the diagnostic test of
      choice for pancreatic lesions. Preoperative clinical management depends on many
      factors, many of which rely on accurate cytologic assessment. Pancreaticobiliary
      cytology is wrought with diagnostic pitfalls. Clinical history, imaging studies,
      cytology samples, and ancillary tests, including immunohistochemistry,
      biochemical analysis, and genetic sequencing, are integral to forming a complete
      diagnosis and guiding optimal patient management. This article reviews clinical
      aspects and the diagnostic work-up of commonly encountered diagnostic entities
      within the field of pancreatic cytology.

PMID- 30190142
TI  - Updates in Cervical Cytology: The 90-Year-Long Journey from Battle Creek to
      Today.
AB  - Ninety years ago, at the Battle Creek conference, Papanicolaou introduced
      cervical exfoliative cytology. Since then, the "Pap test" has come a long way.
      The discovery of a causal relationship between cervical carcinoma and HPV
      infection opened the door for molecular testing and immunomarkers for HPV. The
      Clinical Laboratory Improvement Amendments, 1988, established quality assurance
      and quality control programs to monitor performance of cytology laboratories. The
      Bethesda System for reporting cervical cytology laid the foundations for cervical
      cytology education, implementation of management guidelines, and further research
      on cervical carcinogenesis. HPV vaccine penetration in both genders remains 62%
      or less.

PMID- 30190143
TI  - Diagnostic Advances in Urine Cytology.
AB  - The utility of urine cytology has shifted from the identification of red blood
      cells, crystals, or parasites to its currently used role of detection of cancer
      cells exfoliated in urine samples. A variety of ancillary tests have been
      developed to complement the diagnostic ability of urine cytology. Furthermore,
      urine testing will continue to evolve as the pathogenesis of genitourinary tract
      diseases in depth is understood. This article focuses on the diagnostic advances
      in urine cytology from the cytomorphological perspective, past and current
      reporting schemes, and the application of ancillary testing in urine samples.

PMID- 30190144
TI  - Adult Renal Neoplasms: Cytology, Immunohistochemistry, and Cytogenetic
      Characteristics.
AB  - Tissue sampling of renal masses is traditionally performed using percutaneous
      sonographic or CT guidance core biopsy (CB) with or without touch preparation
      cytology and/or fine-needle aspiration cytology (FNAC). The combined used of CB
      and FNAC is expanding in clinical practice, especially in small renal masses and
      plays a pivotal role in therapeutic decision making. Grouping the renal neoplasms
      in differential diagnostic groups helps in choosing specific immunohistochemical
      markers and reaching an accurate diagnosis.

PMID- 30190145
TI  - Applications of Ancillary Testing in the Cytologic Diagnosis of Soft Tissue
      Neoplasms.
AB  - Soft tissue neoplasms are diagnostically challenging, although many advances in
      ancillary testing now enable accurate classification of fine-needle aspiration
      biopsies by detection of characteristic immunophenotypes (including protein
      correlates of molecular alterations) and molecular features. Although there are
      many useful diagnostic immunohistochemical markers and molecular assays, their
      diagnostic utility relies on correlation with clinical and morphologic features,
      judicious application, and appropriate interpretation because no single test is
      perfectly sensitive or specific. This review discusses applications of ancillary
      testing for commonly encountered soft tissue neoplasms in cytopathologic practice
      in the context of a pattern-based approach.

PMID- 30190146
TI  - Updates in Primary Bone Tumors: Current Challenges and New Opportunities in
      Cytopathology.
AB  - The review summarizes the current diagnostic challenges in fine-needle aspiration
      of primary bone tumors, with focus on the application of new molecular and
      immunohistochemical techniques in the diagnosis of giant cell-rich neoplasms,
      chondrosarcomas, and notochordal tumors.

PMID- 30190148
TI  - Circulating Tumor Cells: Applications in Cytopathology.
AB  - Circulating tumor cells (CTCs) are rare tumor cells found in the blood of
      patients with cancer that can be reliably detected by CTC technologies to provide
      prognostic, predictive, and diagnostic information. CTC sampling reflects
      intratumoral and intertumoral heterogeneity better than targeted biopsy. CTC
      samples are minimally invasive and amenable to repeated sampling, allowing real
      time evaluation of tumor in response to therapy-related pressures and possibly
      early detection. Cytology is the most natural arena for integration of CTC
      testing. CTC technology may also be deployed to enhance and facilitate the
      practice of cytology and surgical pathology.

PMID- 30190147
TI  - Advances in Molecular Testing Techniques in Cytologic Specimens.
AB  - There has been a paradigm shift in the practice of cytopathology with the advent
      of highly sensitive molecular tests using small amounts of tissue that can
      provide diagnostic, prognostic, and predictive information for clinical
      management. The cytopathologist plays a key role in providing a timely and
      accurate diagnosis as well as ensuring appropriate processing and handling of the
      specimen and judicious triaging of the tissue for molecular testing that guide
      therapeutic decisions. As the era of "precision medicine" continues to evolve and
      expand, cytopathology remains a dynamic field with advances in the practice of
      molecular cytopathology providing new paradigms in clinical care.

PMID- 30190149
TI  - Cytopathology: Diagnostic Updates and Advances in Ancillary Testing.

PMID- 30190150
TI  - Erratum to 'Ultrasonography Improves Glycemic Control by Detecting Insulin
      Derived Localized Amyloidosis' [Ultrasound Med Biol 43 (2017) 2284-2294].

PMID- 30190151
TI  - No otoacoustic evidence for a peripheral basis of absolute pitch.
AB  - Absolute pitch (AP) is the ability to identify the perceived pitch of a sound
      without an external reference. Relatively rare, with an incidence of
      approximately 1/10,000, the mechanisms underlying AP are not well understood.
      This study examined otoacoustic emissions (OAEs) to determine if there is
      evidence of a peripheral (i.e., cochlear) basis for AP. Two OAE types were
      examined: spontaneous emissions (SOAEs) and stimulus-frequency emissions
      (SFOAEs). Our motivations to explore a peripheral foundation for AP were several
      fold. First is the observation that pitch judgment accuracy has been reported to
      decrease with age due to age-dependent physiological changes cochlear
      biomechanics. Second is the notion that SOAEs, which are indirectly related to
      perception, could act as a fixed frequency reference. Third, SFOAE delays, which
      have been demonstrated to serve as a proxy measure for cochlear frequency
      selectivity, could indicate tuning differences between groups. These led us to
      the hypotheses that AP subjects would (relative to controls) exhibit a. greater
      SOAE activity and b. sharper cochlear tuning. To test these notions, measurements
      were made in normal-hearing control (N = 33) and AP-possessor (N = 20)
      populations. In short, no substantial difference in SOAE activity was found
      between groups, indicating no evidence for one or more strong SOAEs that could
      act as a fixed cue. SFOAE phase-gradient delays, measured at several different
      probe levels (20-50 dB SPL), also showed no significant differences between
      groups. This observation argues against sharper cochlear frequency selectivity in
      AP subjects. Taken together, these data support the prevailing view that AP
      mechanisms predominantly arise at a processing level in the central nervous
      system (CNS) at the brainstem or higher, not within the cochlea.

PMID- 30190153
TI  - Pathological factors involved in local failure in squamous cell carcinoma of the
      oral cavity: retrospective study and proposal of a new clinical classification.
AB  - The control of local failure (LF) is essential to improve outcomes in patients
      with squamous cell carcinoma of the oral cavity (OSCC). In this study, LF of OSCC
      was classified into three clinical types: deep recurrence (type 1R), adjacent
      superficial recurrence (type 2R), and distant primary tumour (type 3R). LF was
      analyzed after surgical resection of OSCC to determine the validity and
      usefulness of this classification system. Of 257 patients with OSCC, 58
      experienced LF; 21 had type 1R, 23 had type 2R, and 20 had type 3R. Clinical
      factors influencing LF were analyzed by log-rank test and Cox test. Type 1R was
      significantly related to the TN classification, resection margin status, and
      invasive pattern. Type 2R was strongly associated with the grade of epithelial
      dysplasia at the surgical margins. Type 1R rarely developed more than 1year after
      surgery, whereas type 2R did not develop within 2 years. Type 1R may be caused by
      residual cancer cells in the deep margins, and type 2R by precancerous cells
      remaining in the marginal epithelium and gradually becoming invasive cancer. Type
      3R may be considered an independent tumour. The newly proposed clinical
      classification is convenient and roughly reflects the causes and mechanisms of
      relapse.

PMID- 30190152
TI  - Corrigendum to "JWA antagonizes paraquat-induced neurotoxicity via activation of
      Nrf2" [Toxicol. Lett. 277 (August) (2017) 32-40].

PMID- 30190154
TI  - Delay in initiation of DMARD or anti-inflammatory therapy in patients newly
      diagnosed with rheumatoid arthritis: An analysis of United States Military Health
      System TRICARE beneficiaries.
AB  - OBJECTIVE: To investigate factors associated with delay in initiation of initial
      disease-modifying antirheumatic drug (DMARD) in patients newly diagnosed with
      rheumatoid arthritis (RA). METHODS: We performed a retrospective cohort
      descriptive study using administrative data from the US military's TRICARE
      program (2007-2012). We identified incident RA cases using billing codes and
      initial DMARD receipt using prescription fill date. We quantified the time
      between RA presentation and initial DMARD receipt, evaluated temporal changes in
      delay over the study period, and investigated predictors of treatment delay (> 90
      days) using logistic regression. RESULTS: We identified 16,680 patients with
      incident RA that were prescribed DMARDs and mean age was 47.2 (SD 13.5) years.
      The mean time from initial RA presentation to first DMARD prescription receipt
      was 125.3 days (SD 175.4). Over one-third (35.6%) of incident RA patients
      initiated DMARD > 90 days after presentation. There was less treatment delay in
      later years of the study (mean days to DMARD of 144.7 days in 2007; 109.7 days in
      2012). Patients prescribed opioids had mean time to DMARD of 212.8 days (SD
      207.4) compared to mean of 77.3 days (SD 132.3) for those who did not use opioids
      (p < 0.0001). Patients prescribed opioids between RA presentation and initial
      DMARD receipt were more likely to have delay in initial DMARD (OR 4.07, 95% CI:
      3.78-4.37). CONCLUSION: In this large US nationwide study, delays in initial
      DMARD receipt for incident RA were common but time to treatment improved in
      recent years. While further analysis using clinical data is warranted, these
      findings suggest that limiting opioid use in patients newly presenting with RA
      may decrease delay in initiating DMARDs.

PMID- 30190155
TI  - Decompensated right heart failure, intensive care and perioperative management in
      patients with pulmonary hypertension: Updated recommendations from the Cologne
      Consensus Conference 2018.
AB  - In June 2016, members of the German Society of Cardiology (DGK), the German
      Society of Respiratory Medicine (DGP) and the German Society of Pediatric
      Cardiology (DGPK) met for a Consensus Conference in Cologne, Germany. Aim of this
      Conference was to compile consensus based practice recommendations based on the
      2015 European Pulmonary Hypertension guidelines, aiming at their practical
      implementation, considering country-specific issues, and including new evidence,
      where available. This article summarizes the results and updated recommendations
      2018 of the working group on decompensated right heart failure (RHF), intensive
      care and perioperative management in patients with pulmonary hypertension. The
      RHF section comprises definition and pathophysiology, diagnosis and monitoring,
      identification of triggering factors and supportive therapy of RHF, volume
      management as well as PAH targeting therapy, therapy with inotropic, inodilator
      and vasopressor drugs, extracorporeal support and transplantation. The second
      part of this article summarizes preoperative management, perioperative monitoring
      and choice of anesthesia.

PMID- 30190156
TI  - General measures and supportive therapy for pulmonary arterial hypertension:
      Updated recommendations from the Cologne Consensus Conference 2018.
AB  - In the summer of 2016, delegates from the German Respiratory Society, the German
      Society of Cardiology and the German Society of Pediatric Cardiology met in
      Cologne, Germany, to define consensus-based practice recommendations for the
      management of patients with pulmonary arterial hypertension (PAH). These
      recommendations were built on the 2015 European Pulmonary Hypertension guidelines
      aiming at their practical implementation, considering country-specific issues,
      and including new evidence, where available. To this end, a number of working
      groups was initiated, one of which was specifically dedicated to general measures
      (i.e. physical activity/supervised rehabilitation, pregnancy/contraception,
      elective surgery, infection prevention, psychological support, travel) and
      supportive therapy (i.e. anticoagulants, diuretics, oxygen, cardiovascular
      medications, anaemia/iron deficiency, arrhythmias) for PAH. While the European
      guidelines provide detailed recommendations for the use of targeted PAH therapies
      as well as supportive care, detailed treatment decisions in routine clinical care
      may be challenging, and the relevance of supportive care is often not
      sufficiently considered. In addition, new evidence became available, thus
      requiring a thorough reevaluation of specific recommendations. The detailed
      results and recommendations of the working group on general measures and
      supportive therapy for PAH, which were last updated in the spring of 2018, are
      summarized in this article.

PMID- 30190157
TI  - Pulse pressure and selection of the optimal coronary artery disease management
      strategy in patients with type 2 diabetes.

PMID- 30190158
TI  - Targeted therapy of pulmonary arterial hypertension: Updated recommendations from
      the Cologne Consensus Conference 2018.
AB  - In the summer of 2016, delegates from the German Respiratory Society, the German
      Society of Cardiology and the German Society of Pediatric Cardiology met in
      Cologne, Germany, to define consensus-based practice recommendations for the
      management of patients with pulmonary arterial hypertension (PAH). These
      recommendations were built on the 2015 European Pulmonary Hypertension guidelines
      and included new evidence, where available. The treatment algorithm for PAH was
      modified based on the observation that there are now many patients diagnosed with
      IPAH who are at an advanced age and have significant cardiopulmonary
      comorbidities. For patients newly diagnosed with classic forms of PAH, i.e.
      younger patients without significant cardiopulmonary comorbidities, the consensus
      based recommendation was to use initial combination therapy as the standard
      approach. The use of monotherapies was no longer considered appropriate in such
      patients. The choice of treatment strategies should be based on the risk
      assessment as proposed in the European guidelines. In patients presenting with a
      low or intermediate risk, oral combination therapy with endothelin receptor
      antagonists and phosphodiesterase-5 inhibitors or soluble guanylate cyclase
      stimulators, respectively, should be used. In high-risk patients, triple
      combination therapy including a subcutaneous or intravenous prostacyclin analogue
      should be considered. For patients who suffer from PAH and significant
      cardiopulmonary comorbidities, initial monotherapy is recommended and the use of
      combination therapies should be considered on an individual basis. The latter
      recommendations are based on the scarcity of evidence supporting the use of
      combination therapy and the higher risk of drug-related adverse events in such
      patients.

PMID- 30190159
TI  - The LifeLines Cohort Study: Prevalence and treatment of cardiovascular disease
      and risk factors.

PMID- 30190160
TI  - Does renal function have incremental predictive value of stroke in atrial
      fibrillation?

PMID- 30190161
TI  - Screening for extended-spectrum beta-lactamase-producing Enterobacteriaceae
      intestinal carriage among children aged under five in Lome, Togo.

PMID- 30190162
TI  - [Bordetella trematum bacteremia in an immunosuppressed patient].

PMID- 30190163
TI  - A fatal case of Streptococcus uberis endocarditis on cardiovascular implantable
      electronic device.

PMID- 30190164
TI  - Multidisciplinary management of patients presenting with Lyme disease suspicion.
AB  - OBJECTIVE: The teaching hospital of Nancy, France, implemented a specific
      multidisciplinary care pathway (French acronym AMDPL) to improve the management
      of patients presenting with Lyme borreliosis (LB) suspicion. We aimed to assess
      the first year of activity of this care pathway. PATIENTS AND METHODS: We
      included all patients managed in the AMDPL pathway from November 1, 2016 to
      October 31, 2017. The first step was a dedicated Lyme disease consultation with
      an infectious disease specialist. Following this consultation, the LB diagnosis
      was either confirmed and adequate treatment was prescribed, or a differential
      diagnosis was established and patients received adequate management, or further
      investigations were required and patients were offered multidisciplinary
      management as part of a day hospitalization. RESULTS: A total of 468 patients
      were included. LB diagnosis was confirmed in 15% of patients (69/468), 49% of
      patients received a differential diagnosis, and 26% (122/468) of patients had the
      LB diagnosis ruled out without receiving any other diagnosis. CONCLUSIONS: This
      is to our knowledge the first multidisciplinary center implemented in France for
      the management of patients presenting with LB suspicion related to polymorphous
      signs and symptoms. Several diagnoses could be confirmed or corrected, although
      some symptoms and complaints could not be explained. This cohort could improve
      our knowledge of LB and its differential diagnoses.

PMID- 30190165
TI  - A phase 2, randomized, placebo-controlled study of the efficacy and safety of TAK
      063 in subjects with an acute exacerbation of schizophrenia.
AB  - INTRODUCTION: TAK-063 is a potent, selective inhibitor of phosphodiesterase 10A,
      an enzyme selectively expressed in medium spiny neurons of the striatum. This
      randomized, parallel-group study evaluated the efficacy and safety of 20-mg daily
      TAK-063 versus placebo in subjects with acutely exacerbated symptoms of
      schizophrenia (NCT02477020). METHODS: Adults aged 18 to 65 with diagnosed
      schizophrenia and psychotic symptoms that exacerbated within 60 days before
      screening were included. Subjects who discontinued psychotropic medications
      before screening were randomized 1:1 to 6 weeks of placebo (n = 81) or 20-mg TAK
      063 (n = 83). Weekly efficacy visits were conducted during the treatment period,
      and dose de-escalation was allowed (blinded) to 10-mg TAK-063 for intolerability.
      RESULTS: The primary endpoint, change from baseline in the Positive and Negative
      Syndrome Scale total score at week 6, was not achieved (least-squares mean
      difference vs placebo [standard error] = -5.46 [3.44]; p = 0.115). Secondary
      endpoints were generally supportive of antipsychotic efficacy. Consistent with
      previous phase 1 studies, TAK-063 was safe and well tolerated, and most adverse
      events were mild or moderate in severity and did not result in discontinuation.
      No deaths occurred, and the incidence of akathisia and dystonia, categories of
      extrapyramidal syndromes, was more frequent in the TAK-063 group than placebo.
      CONCLUSIONS: Although the study did not meet the primary endpoint (effect size =
      0.308), the effects of TAK-063 on the primary and secondary endpoints may be
      suggestive of antipsychotic activity. Interpretation of these results is
      confounded by a relatively high placebo effect and a lack of dose-ranging or
      active reference.

PMID- 30190168
TI  - Non invasive mechanical ventilation in DM1: The strong correlation between lung
      function, neurological-cognitive function and CTG repeats.

PMID- 30190167
TI  - The impact of trauma exposure on the development of PTSD and psychological
      distress in a volunteer fire service.
AB  - Emergency service workers (ESWs) are at increased risk of trauma-related mental
      disorders. However, volunteer ESWs, who comprise the majority of firefighters in
      Western countries, have limited access to the necessary support services for
      mental health problems. This study aimed to examine the impact of the level and
      types of trauma exposure on the development of mental disorders in a volunteer
      fire service. Members of an Australian volunteer fire service (N = 459) completed
      a cross-sectional survey. Information on the number and types of distressing
      critical incidents involved within the last year was collected. Validated, self
      report measures were used to determine probable post-traumatic stress disorder
      (PTSD) and psychological distress caseness. The risk of probable PTSD was
      significantly higher for those with the most frequent involvement with
      distressing incidents and the highest levels of cumulative trauma exposure. Being
      trapped in a dangerous situation or being assaulted by other people, resulted in
      the greatest odds of developing a mental disorder. Volunteer fire service members
      with the highest levels of trauma exposure and involvement with particular types
      of critical incidents are at elevated risk of mental health problems. The
      implications for the provision of psychological support measures amongst
      volunteer emergency services are discussed.

PMID- 30190166
TI  - Comparison of three moderate fractionated schedules employed in high-dose-rate
      brachytherapy monotherapy for clinically localized prostate cancer.
AB  - BACKGROUND: Herein, we report the outcomes of 3 schedules of high-dose-rate
      interstitial brachytherapy (HDR-BT) monotherapy for localized prostate cancer.
      PATIENTS AND METHODS: A total of 347 patients were treated with 45.5 Gy/7
      fractions (n = 86; 45.5 Gy arm, median follow-up time 131 months), 49 Gy/7
      fractions (n = 149; 49 Gy arm, 75.9 months), and 54 Gy/9 fractions (n = 112; 54
      Gy arm, 68 months). RESULTS: The actuarial 5-year biochemical failure-free
      survival rates were 86.8%, 94.1%, and 88.5% (p = 0.2023) for the 45.5 Gy, 49 Gy,
      and 54 Gy arms in the high-risk group; 90.4%, 100%, and 97.4% (p = 0.0818) in the
      intermediate-risk group; and not available, 100%, and 100% in the low-risk group,
      respectively. The 5-year distant metastasis-free (and overall) survival rates
      were 94.4%, 98.2%, and 96.3% (100%, 92.8%, and 99.1%) for the 45.5 Gy, 49 Gy, and
      54 Gy arms (p = 0.5454 and p = 0.0028), respectively. At 5 years, accumulated
      incidence of grade >=2 gastrointestinal toxicity was 1.2%, 2.7%, and 3.4% for the
      45.5 Gy, 49 Gy, and 54 Gy arms (p = 0.5605), respectively. For genitourinary
      toxicity, the 49 Gy arm showed a higher grade >=2 toxicity of 20.5% than those
      observed in the 45.5 Gy (2.4%) and 54 Gy arms (10.1%). No grade 4 or 5 of either
      type of toxicity was detected. CONCLUSIONS: The 3 schedules showed equivocal
      outcomes in each risk group, with different toxicity profiles. HDR-BT monotherapy
      with these schedules is an acceptable treatment option for localized prostate
      cancer.

PMID- 30190169
TI  - Characterizing export of land-based microplastics to the estuary - Part II:
      Sensitivity analysis of an integrated geospatial microplastic transport modeling
      assessment of tire and road wear particles.
AB  - Integrated models addressing microplastic (MP) generation, terrestrial
      distribution, and freshwater transport are useful tools characterizing the export
      of MP to marine waters. In Part I of this study, a baseline watershed-scale MP
      mass balance model was developed for tire and road wear particles (TRWP) in the
      Seine watershed. In Part II, uncertainty and sensitivity analysis (SA) methods
      were used to identify the parameters that determine the transport of these
      particles to the estuary. Local differential, local range and global first-order
      variance-based SA identified similar key parameters. The global SA (1000 Monte
      Carlo simulations) indicated that most of the variance in TRWP exported to the
      estuary can be apportioned to TRWP diameter (76%), TRWP density (5.6%), the
      fraction of TRWP directed to combined sewers with treatment (3.9%), and the
      fraction of TRWP distributed to runoff (versus roadside soil; 2.2%). The export
      fraction was relatively insensitive to heteroaggregation processes and the
      rainfall intensity threshold for road surface washoff. The fraction of TRWP
      exported to estuary in the probabilistic assessment was centered on the baseline
      estimate of 2%. This fraction ranged from 1.4 to 4.9% (central tendency defined
      as 25th to 75th percentile) and 0.97% to 13% (plausible upper bound defined as
      10th to 90th percentiles). This study emphasizes the importance of in situ
      characterization of TRWP diameter and density, and confirms the baseline mass
      balance presented in Part I, which indicated an appreciable potential for capture
      of TRWP in freshwater sediment.

PMID- 30190170
TI  - Novel epigenetic-sensitive clinical challenges both in type 1 and type 2
      diabetes.
AB  - BACKGROUND: Epigenetics modulated tissue-specific gene expression during the
      onset of type 1 and type 2 diabetes and their complications. METHODS: We searched
      the PubMed recent studies about the main epigenetic tags involved in type 1 and
      type 2 diabetes onset and their clinical complications. PubMed studies about the
      epigenetic tags involved in type 1 and 2 diabetes onset was searched. RESULTS:
      The epigenetic methylation maps of cord blood samples highlighted differences in
      the methylation status of CpG sites within the MHC genes between carriers of
      diabetes type 1 DR3-DQ2 and DR4-DQ8 risk haplotypes. beta cell-derived
      unmethylated INS DNA showed the decline of beta-cell mass preserving insulin
      secretion. Differentially methylated regions in pancreatic islets from type 2
      diabetes covered PDX1, TCF7L2, and ADCY5 promoters during islet dysfunction. The
      recruitment of SET7 and SUV39H1 histone methyltransferases and LSD-1 lysine
      specific demethylase-1 at NF-kbeta-p65 promoter in vascular cells was involved in
      coronary heart disease. Neutrophil extracellular trap, activated by protein
      arginine deiminase-4, impaired wound healing from diabetic foot ulcers. MiR-199a
      3p over-expression induced coagulative cascade, swelling and pain by a down
      regulation of SERPIN-E2 in diabetic peripheral neuropathy. A DNA hypo-methylation
      and histone hyper-acetylation at MIOX promoter led an overexpression of ROS,
      fibronectin, HIF-1alpha, and NOX-4 associated with diabetic tubulopathy. A hypo
      methylation of H3K4 at SOD2 promoter by LSD-1 increased ROS causing diabetic
      retinopathy. CONCLUSIONS: Epigenetics played a relevant role in prevention,
      diagnosis, and treatment of diabetes.

PMID- 30190171
TI  - Lentivirus-mediated knockdown of FcgammaRI (CD64) attenuated lupus nephritis via
      inhibition of NF-kappaB regulating NLRP3 inflammasome activation in MRL/lpr mice.
AB  - Lupus nephritis, one of the most serious complications of systemic lupus
      erythematosus (SLE), has been confirmed in a large number of clinical surveys.
      Current studies have suggested that inflammatory situation is generally
      considered to facilitate the occurrence and development of lupus nephritis.
      Previous research found that Fcgamma receptor I (FcgammaRI) was compulsory for
      several autoimmune and inflammatory diseases, and it might be involved in the
      treatment of lupus nephritis. Furthermore, the possible molecular mechanism of
      the role of FcgammaRI in lupus nephritis still needs a further study. In the
      present study, in order to evaluate the effect of FcgammaRI on kidney function in
      lupus-prone MLR/lpr mice, FcgammaRI knockdown was implemented utilizing FcgammaRI
      RNAi lentivirus. We reported that the administration of FcgammaRI-RNAi lentivirus
      (1) mainly inhibited FcgammaRI expression on macrophage of the kidneys, lowered
      the levels of urinary protein and serum anti-dsDNA antibody and prevented the
      impairment of renal function; (2) reduced the renal inflammatory cytokines (IL
      1beta and IL-18); (3) decreased NF-kappaB p65 nuclear migration, suppressed NOD
      like receptor protein 3 (NLRP3) inflammasome activation, and finally inhibited
      renal inflammation. Together, these results showed the role of FcgammaRI on
      macrophages to involve in renal inflammatory response, potentially via regulating
      the NLRP3 inflammasome-associated signaling.

PMID- 30190172
TI  - The angiotensin II type 2 receptors protect renal tubule mitochondria in early
      stages of diabetes mellitus.
AB  - Diabetic nephropathy correlates more closely to defective mitochondria and
      increased oxidative stress in the kidney than to hyperglycemia. A key driving
      factor of diabetic nephropathy is angiotensin II acting via the G-protein-coupled
      cell membrane type 1 receptor. The present study aimed to investigate the role of
      the angiotensin II type 2 receptor (AT2R) at the early stages of diabetic
      nephropathy. Using receptor binding studies and immunohistochemistry we found
      that the mitochondria in renal tubules contain high-affinity AT2Rs. Increased
      renal mitochondrial AT2R density by transgenic overexpression was associated with
      reduced superoxide production of isolated mitochondria from non-diabetic rats.
      Streptozotocin-induced diabetes (28 days) caused a drop in the ATP/oxygen ratio
      and an increase in the superoxide production of isolated renal mitochondria from
      wild-type diabetic rats. This correlated with changes in the renal expression
      profile and increased tubular epithelial cell proliferation. AT2R overexpression
      in tubular epithelial cells inhibited all diabetes-induced renal changes
      including a drop in mitochondrial bioenergetics efficiency, a rise in
      mitochondrial superoxide production, metabolic reprogramming, and increased
      proliferation. Thus, AT2Rs translocate to mitochondria and can contribute to reno
      protective effects at early stages of diabetes. Hence, targeted AT2R
      overexpression in renal cells may open new avenues to develop novel types of
      drugs preventing diabetic nephropathy.

PMID- 30190174
TI  - New diagnostic modalities and emerging treatments for neonatal bone disease.
AB  - Bone disease in the neonatal period has often been regarded as an issue affecting
      premature infants, or a collection of rare and ultra-rare disorders that most
      neonatologists will see only once or twice each year, or possibly each decade.
      The emergence of targeted therapies for some of these rare disorders means that
      neonatologists may be faced with diagnostic dilemmas that need a rapid solution
      in order to access management options that did not previously exist. The
      diagnostic modalities available to the neonatologist have not changed a great
      deal in recent years; blood tests and radiographs still form the mainstays with
      other techniques usually reserved for research studies, but rapid access to
      genomic testing is emergent. This paper provides an update around diagnosis and
      management of bone problems likely to present to the neonatologist.

PMID- 30190175
TI  - In vivo efficacy of biocompatible silver nanoparticles cream for empirical wound
      healing.
AB  - Wound healing is a complicated process that begins at the onset of injury and a
      continued process till complete healing. The emergence of nanotechnology has
      provided a new therapeutic modality to silver nanoparticles in treatment of
      wounds. However, the safety of these silver nanoparticles in the process of wound
      healing is yet to be elucidated; nevertheless, biocompatibility is the primary
      concern. Biosynthesis of silver nanoparticles was synthesized using aqueous clove
      extract and silver nitrate solution under microwave and the obtained particles
      size were 30-60 nm and roughly spherical in shape. The present study focused on
      the efficacy of biocompatible silver nanoparticles in vivo wound healing process.
      Consequently, this study supported the incorporation of biosynthesized silver
      nanoparticles in wound dressings as a cream formulation for improved healthcare.

PMID- 30190173
TI  - Rictor deficiency in dendritic cells exacerbates acute kidney injury.
AB  - Dendritic cells (DCs) are critical initiators of innate immunity in the kidney
      and orchestrate inflammation following ischemia-reperfusion injury. The role of
      the mammalian/mechanistic target of rapamycin (mTOR) in the pathophysiology of
      renal ischemia-reperfusion injury has been characterized. However, the influence
      of DC-based alterations in mTOR signaling is unknown. To address this, bone
      marrow-derived mTORC2-deficient (Rictor-/-) DCs underwent hypoxia-reoxygenation
      and then analysis by flow cytometry. Adoptive transfer of wild-type or Rictor-/-
      DC to C57BL/6 mice followed by unilateral or bilateral renal ischemia-reperfusion
      injury (20 min ischemia) was used to assess their in vivo migratory capacity and
      influence on tissue injury. Age-matched male DC-specific Rictor-/- mice or
      littermate controls underwent bilateral renal ischemia-reperfusion, followed by
      assessment of renal function, histopathology, and biomolecular and cell
      infiltration analysis. Rictor-/- DCs expressed more costimulatory CD80/CD86 but
      less coinhibitory programmed death ligand 1 (PDL1), a pattern that was enhanced
      by hypoxia-reoxygenation. They also demonstrated enhanced migration to the
      injured kidney and induced greater tissue damage. Following ischemia-reperfusion,
      Rictor-/- DC mice developed higher serum creatinine levels, more severe
      histological damage, and greater proinflammatory cytokine production compared to
      littermate controls. Additionally, a greater influx of both neutrophils and T
      cells was seen in Rictor-/- DC mice, along with CD11c+MHCII+CD11bhiF4/80+ renal
      DC, that expressed more CD86 but less PDL1. Thus, DC-targeted elimination of
      Rictor enhances inflammation and migratory responses to the injured kidney,
      highlighting the regulatory roles of both DCs and Rictor in the pathophysiology
      of acute kidney injury.

PMID- 30190176
TI  - Biochemical characterization of isoprene synthase from Ipomoea batatas.
AB  - The bio-production process of isoprene, an essential chemical used in industry,
      is strongly limited by isoprene synthase. In our previous work, relatively high
      isoprene production was observed with isoprene synthase from Ipomoea batatas
      (IspSib). In this work the biochemical properties of IspSib were analyzed and
      compared with those of isoprene synthase from Populus alba (IspSpa) and other
      species. Firstly, IspSib and IspSpa were expressed, purified, and identified by
      SDS-PAGE and western blot analysis. Secondly, pH and temperature dependence of
      IspSib were performed and an optimum pH of 8.6 and an optimum temperature of 42 
      degrees C were resulted. Mg2+ with optimum concentration of 56 mM was proved to
      be needed for enzyme activation. In addition, in vivo and in vitro study of the
      thermostabilities of IspSib and IspSpa were performed. The enzyme activity of
      IspSib and IspSpa dropped very rapidly after incubation at 30  degrees C; almost
      80% enzyme activity of IspSib was lost after 20 min of incubation. Moreover, the
      Michaelis-Menten constant was measured. IspSib showed a lower Km, 0.2 mM, and a
      higher kcat, 0.37 s-1, as compared with IspSpa. The high catalytic efficiency,
      which was reflected by the high kcat/Km ratio, indicates that IspSib is a good
      candidate for the bio-isoprene production, while its thermal instability remains
      as a challenge. Enzyme engineering efforts, such as direction evolution or semi
      rational evolution, are planned for further research.

PMID- 30190178
TI  - Diffuse Cranial Nerve Involvement in a Patient With Early Infantile Krabbe
      Disease.

PMID- 30190177
TI  - Physician attitudes about genetic testing for localized prostate cancer: A
      national survey of radiation oncologists and urologists.
AB  - INTRODUCTION: Genetic testing has been recently put forth as a strategy to
      improve decision-making in the management of localized prostate cancer. Little is
      known about how frequently prostate cancer specialists are using these tests, or
      whether they consider them important or effective. We performed a national survey
      of radiation oncologists and urologists on their perceptions and self-reported
      use of genetic testing. METHODS: From January to July 2017, a 4-wave mail survey
      was performed involving 915 radiation oncologists and 940 urologists about
      genetic testing and decision-making for localized prostate cancer. The survey
      queried the frequency and type of genetic test and the degree of importance and
      confidence of such tests. Pearson chi-square and multivariable logistic
      regression analyses were performed to identify respondent characteristics
      associated with outcomes. RESULTS: Overall response rate was 37.3% (n = 691). One
      in six specialists reported frequently using genetic tests with urologists more
      likely than radiation oncologists to do so (26% vs. 4%; OR: 3.51, p < 0.001) and
      their perceived higher importance (46% vs. 20%; adjusted OR: 3.51, p < 0.001) as
      well as their confidence in doing so (70% vs. 39%; OR: 3.81, p < 0.001) for
      decision-making for localized prostate cancer. Prolaris and Oncotype represented
      the most commonly cited tumor-based genetic testings. CONCLUSIONS: Few radiation
      oncologists and urologists report frequently using genetic testing for treatment
      decision-making among patients diagnosed with localized prostate cancer, though
      more urologists use these tests and believe they yield meaningful results.

PMID- 30190179
TI  - Clinical Characteristics and Burden of Illness in Pediatric Patients with
      Narcolepsy.
AB  - BACKGROUND: Narcolepsy is a chronic and lifelong neurologic disorder with onset
      commonly occurring in childhood or adolescence, and affecting approximately
      0.025% to 0.05% of the general population. The primary symptom is excessive
      daytime sleepiness, which is accompanied by cataplexy in 70% of patients. Other
      common symptoms include sleep paralysis, hallucinations upon falling asleep or
      waking, and disrupted nocturnal sleep. Narcolepsy is associated with a
      considerable burden of illness (BOI), which has been well characterized in
      adults, and is exacerbated by delays in symptom recognition, diagnosis, and
      intervention. METHODS: This review describes the specific characteristics and BOI
      of pediatric narcolepsy, using a wide range of published research data. RESULTS:
      Pediatric narcolepsy presents distinct challenges in diagnosis and management.
      Narcolepsy symptoms often initially manifest differently in children and
      adolescents versus adults, which may pose diagnostic dilemmas. Children often
      respond to sleepiness with irritability, hyperactivity, and poor attention, which
      may be misinterpreted as misbehavior or neurocognitive sequelae of other
      conditions. Pediatric cataplexy symptoms may include subtle and unusual facial
      expressions or choreic-like movements, which are not observed in adults.
      Insufficient sleep and circadian rhythm disorders presenting with excessive
      daytime sleepiness are common in adolescents, potentially confounding narcolepsy
      diagnosis. Pediatric narcolepsy is also associated with comorbidities including
      rapid weight gain, precocious puberty, and attention deficit hyperactivity
      disorder, and increased risk for deficits in social functioning, depression, and
      anxiety. School performance is also typically impaired, requiring special
      education services. CONCLUSIONS: Thus, the discrete BOI of pediatric narcolepsy
      underscores the need for prompt and accurate diagnosis, and appropriate treatment
      of this disorder.

PMID- 30190181
TI  - Design, synthesis, and biological evaluation of selective and potent Carbazole
      based butyrylcholinesterase inhibitors.
AB  - Alzheimer's disease (AD) is the most common form of dementia. Inhibition of BChE
      might be a useful therapeutic target for AD. A new series of Carbazole-Benzyl
      Pyridine derivatives were designed synthesized and evaluated as
      butyrylcholinesterase (BChE) inhibitors. In vitro assay revealed that all of the
      derivatives had selective and potent anti- BChE activities. 3-((9H-Carbazol-9
      yl)methyl)-1-(4-chlorobenzyl)pyridin-1-ium chloride (compound 8f) had the most
      potent anti-BChE activity (IC50 value = 0.073 MUM), the highest BChE selectivity
      and mixed-type inhibition. Docking study revealed that 8f interacted with the
      peripheral site, the choline binding site, catalytic site and the acyl pocket of
      BChE. Physicochemical properties were accurate to Lipinski's rule. In addition,
      compound 8f demonstrated neuroprotective activity at 10 uM. This compound could
      also inhibit AChE-induced and self-induced Abeta peptide aggregation at
      concentration of 100 uM and 10 uM respectively. The in-vivo study showed that
      compound 8f in 10 mg/kg increased the time spent in target quadrant in the probe
      day and decreased mean training period scape latency in rats. All results suggest
      that new sets of potent selective inhibitors of BChE have a therapeutic potential
      for the treatment of AD.

PMID- 30190180
TI  - Hammersmith Infant Neurological Examination Asymmetry Score Distinguishes
      Hemiplegic Cerebral Palsy From Typical Development.
AB  - BACKGROUND: The Hammersmith Infant Neurological Examination is one of several
      useful tools for early identification of cerebral palsy; however, cut-off scores
      for cerebral palsy do not consistently distinguish infants with hemiplegia from
      those typically developing. We hypothesized that use of an asymmetry score, in
      addition to the assessment's standard total cutoff score, could remedy this
      problem in a clinical setting. METHODS: This retrospective study of a neonatal
      intensive care follow-up program with consistent clinical use of the Hammersmith
      Infant Neurological Examination matched infants with a diagnosis of cerebral
      palsy to infants without motor delays or evidence of neurodevelopmental
      impairments. Groups had same corrected and gestational ages at Hammersmith Infant
      Neurological Examination assessment. Asymmetry presence was recorded. RESULTS: Of
      74 infants with cerebral palsy, 28 had quadriplegia, 11 had diplegia, and 35 had
      hemiplegia. Median total Hammersmith Infant Neurological Examination and
      asymmetry scores for hemiplegia were 57.5 and 10 versus 76 and 0 for those
      without cerebral palsy. Sensitivity and specificity to distinguish hemiplegia
      from typical development by combining a total Hammersmith Infant Neurological
      Examination score less than 63 and an asymmetry score greater than 5 were 91.8%
      and 100%, respectively. CONCLUSIONS: In a clinical setting, combining total
      Hammersmith Infant Neurological Examination and asymmetry scores can help
      providers differentiate infants with hemiplegia from those typically developing.

PMID- 30190182
TI  - Efflux pump inhibition by 11H-pyrido[2,1-b]quinazolin-11-one analogues in
      mycobacteria.
AB  - Mycobacterium tuberculosis infection causes 1.8 million deaths worldwide, of
      which half a million has been diagnosed with resistant tuberculosis (TB).
      Emergence of multi drug resistant and extensive drug resistant strains has made
      all the existing anti-TB therapy futile. The major involvement of efflux pump in
      drug resistance has made it a direct approach for therapeutic exploration against
      resistant M. tuberculosis. This study demarcates the role of 11H-pyrido[2,1
      b]quinazolin-11-one (quinazolinone) analogues as efflux pump inhibitor in
      Mycobacterium smegmatis. Sixteen quinazolinone analogues were synthesized by
      treating 2-aminopyridine and 2-fluorobenzonitrile with KtOBu. Analogues were
      tested, and 3a, 3b, 3c, 3g, 3j, 3l, 3m, and 3p were found to modulate EtBr MIC by
      >4 whereas 3a, 3g, 3i and 3o showed >4 modulation on norfloxacin MIC. 3l and 3o
      in addition to their very low toxicity they showed high EtBr and norfloxacin
      accumulation respectively. Time kill curve showed effective log reduction in
      colony forming unit in presence of these analogues, thus confirming their role as
      efflux pump inhibitor. Through docking and alignment studies, we have also shown
      that the LfrA amino acid residues that the analogues are interacting with are
      present in Rv2333c and Rv2846c of M. tuberculosis. This study have shown for the
      first time the possibility of developing the 11H-pyrido[2,1-b]quinazolin-11-one
      analogues as efflux pump inhibitors for M. smegmatis and hence unbolts the scope
      to advance this study against resistant M. tuberculosis as well.

PMID- 30190184
TI  - Corrigendum to "Unmodified and multi-walled carbon nanotube modified tetrahedral
      amorphous carbon (ta-C) films as in vivo sensor materials for sensitive and
      selective detection of dopamine" [Bios. Bioelectron. 118 (2018) 23-30].

PMID- 30190185
TI  - Adolescent Stress Management in a Primary Care Clinic.
AB  - INTRODUCTION: The American Academy of Pediatrics recommends that adolescents be
      screened for mental health concerns and receive anticipatory guidance on stress
      management strategies. METHODS: Eighty-six participants (50 participants in the
      intervention group; 36 participants in the control group) participated in the
      study. Intervention group participants received training in diaphragmatic
      breathing, progressive muscle relaxation, and use of no-cost/low-cost exercise
      options. Biofeedback was used to guide relaxation. Subjective distress and heart
      rate variability was measured before and after the intervention. RESULTS: After
      the intervention, decreased levels of perceived stress and increased heart rate
      variability were reported compared with the control group. DISCUSSION: This study
      show that an integrated care model in a primary care setting is feasible and
      effective at improving stress management.

PMID- 30190183
TI  - ERG alterations and mTOR pathway activation in primary prostate carcinomas
      developing castration-resistance.
AB  - INTRODUCTION: One of the most common sites of distant metastasization of prostate
      cancer is bone, but to date reliable biomarkers able to predict the risk and
      timing of bone metastasization are still lacking. PATIENTS AND METHODS:
      Surgically resected paraffin embedded samples from 12 primary prostate cancers
      that developed metachronous bone metastasis at different time points were studied
      (six cases within 2 years, six cases after 5 years from surgery). A targeted next
      generation DNA and RNA sequencing able to assess simultaneously mutations, copy
      number alterations and fusion events of multiple genes was used.
      Immunohistochemistry was used to assess mTOR pathway activation. RESULTS:
      Rearrangements of ETS family genes, molecular alterations in PTEN and TP53 genes
      were detected in 10, 6 and 5 cancers, respectively. Nine samples showed TMPRSS2
      ERG fusions, which were associated with increased ERG expression at
      immunohistochemistry. mTOR pathway activation was documented in 6 patients, with
      a clear trend of prevalence in late-metastatic patients (p = 0.08). CONCLUSIONS:
      A simultaneous next-generation targeted DNA and RNA sequencing is applicable on
      routine formalin-fixed paraffin-embedded tissues to assess the multigene
      molecular asset of individual prostate cancers. This approach, coupled with
      immunohistochemistry for ERG and mTOR pathway proteins, may help to better
      characterize prostate cancer molecular features with a potential impact on
      clinical decisions.

PMID- 30190186
TI  - Child Maltreatment Red Flags: Two Cases of Bruising in Premobile Infants.
AB  - Child maltreatment is a serious public health concern in the United States. Young
      infants and children younger than 3 years are at the highest risk of being abused
      and can experience both acute injuries and long-term developmental, behavioral,
      and mental health problems. Health care providers are mandated reporters of
      suspected abuse but may misdiagnose potentially abusive injuries because of lack
      of knowledge in recognizing maltreatment. Premobile infants rarely have bruising
      or intraoral injuries without a reported accident or underlying systemic disease
      and should raise concern for abuse. It is not uncommon for an abused child to
      present with an injury that at first glance may seem trivial but is actually
      suspicious for physical abuse and later be found to have abusive fractures or
      head trauma. The following case presentations show the importance of recognizing
      sentinel injuries and red flags for maltreatment in young, premobile infants with
      unexplained bruises.

PMID- 30190187
TI  - Integrating RNA-seq and GWAS reveals novel genetic mutations for buffalo
      reproductive traits.
AB  - Genome-wide association study (GWAS) has been applied in buffalo breeding
      programs and been used to identify a number of candidate genes associated with
      buffalo reproductive traits. The genetic code of specific genes underlying
      buffalo reproductive traits remains unclear. Association study that measures both
      genetic and transcriptional variation has been applied for the investigation of
      complex traits. To investigate genes involved in buffalo reproductive traits,
      integrated RNA-seq results were investigated of buffalo granulosa cells and
      candidate genes which were reported to be associated with buffalo reproductive
      traits in a previous GWAS. A large number of variants were detected by RNA-seq,
      and 214 variants were located within the buffalo reproductive candidate genes
      identified by GWAS. A further association study in 462 Italian Mediterranean
      buffalo indicated that 25 SNPs distributed in 13 genes were associated with
      reproductive traits. Of the 13 genes, 11 were expressed in granulosa cells of all
      antral follicle development stages, and significant difference was found in the
      expression of NDUFS2 between follicles of diameter <8 mm and > 8 mm. These
      findings extend the results of GWAS by expanding the knowledge about new and
      potentially functional single-nucleotide polymorphisms and provide useful
      information about regulatory genes affecting buffalo reproductive traits.

PMID- 30190188
TI  - Childhood Obesity: An Unresolved Issue.

PMID- 30190189
TI  - MR imaging-guided prostate interventional imaging: Ready for a clinical use?
AB  - Prostate interventional magnetic resonance imaging (MRI) is now routinely
      performed in many centers. Its more widespread acceptance is limited by the cost
      of the use of MRI largely related to the long duration time of the procedures.
      However, the benefit of a robotic assistance has generated a new interest,
      because it substantially shortens the procedure time, while improving the
      accuracy. MRI-guided biopsy is considered as an appealing alternative to
      transrectal ultrasound (TRUS)-guided fusion biopsy, given the limitations of TRUS
      MRI image registration systems. MRI-guided focal treatment also benefits from
      robotic assistance and from the unique property of MRI, which allows the
      measurement of the temperature in real-time during tumor ablation. The
      transrectal and transperineal approaches can be used and the respective
      indications of each pathway will depend on several factors, including the
      location of the tumor and the examination time, which will condition the
      occupation time of the MR room, a major factor influencing the overall cost of
      MRI-guided procedures. This review addresses the current practice of prostate MRI
      guided interventional procedures and potential future applications.

PMID- 30190190
TI  - Interference of Contralateral Permanent Pacemaker Placement With Emergent Central
      Venous Access.

PMID- 30190191
TI  - An Unusual Pulmonary Complication in Spinal Tuberculosis.

PMID- 30190192
TI  - Analysis of Temporal and Causal Relationship Between Syncope and 30-Day Events in
      a Cohort of Emergency Department Patients to Identify the True Rate of Short-term
      Outcomes.
AB  - BACKGROUND: There are a limited number of studies on the short-term prognosis of
      syncopal patients, and those available are heterogeneous and often have
      considered events without a clear relationship with the syncopal episode as
      serious outcomes. OBJECTIVE: The aim of this study was to identify the incidence
      of short-term true outcomes of a syncopal episode, only considering those
      occurring after a reasonable period of time, with a plausible causal relationship
      with index syncope as well as syncopal recurrences causing major trauma. METHODS:
      In this retrospective, observational study, we assessed all patients managed in
      the emergency department (ED) during a 6-month period, with 30 days of follow-up.
      RESULTS: The study population consisted of 982 consecutive syncopal patients. We
      observed short-term serious events, in a broad sense, in 154 patients (15.7%),
      the most frequent being dysrhythmias (20.8%), cerebrovascular accidents (18.2%),
      major traumatic injuries (16.2%), death (13%), and myocardial infarction (9.7%).
      Most of these events (63.6%) could be identified within 72 h, mainly in the ED.
      Only 19 patients (2.2% of the sample), experienced a true short-term outcome (7
      deaths, 1 myocardial infarction, 9 dysrhythmias, 1 major bleeding event, and 1
      traumatic syncopal recurrence). CONCLUSIONS: The incidence of short-term true
      outcomes of syncope is extremely low. Distinguishing true outcomes from other
      events has a crucial significance for understanding the real prognostic role of
      syncope and for planning ED management. Once patients with syncope as a direct
      consequence of an acute disease needing admission by itself are excluded, most
      patients with unexplained syncope could be safely discharged after primary
      evaluation and brief ED monitoring.

PMID- 30190194
TI  - Vitamin A and Breast Cancer Survival: A Systematic Review and Meta-analysis.
AB  - BACKGROUND: The association between vitamin A intake and breast cancer survival
      has been inconsistent. We conducted a systemic review and meta-analysis to
      summarize the results on the association between dietary or supplement vitamin A
      and its derivatives and breast cancer-specific survival and overall survival
      (OS). MATERIALS AND METHODS: A comprehensive search of PubMed and EMBASE was
      performed from inception to January 31, 2018. The summary hazard ratios and 95%
      confidence intervals were estimated using a random effects model. RESULTS: Ten
      studies (8 cohort, 1 clinical trial, and 1 of pooled studies), with 19,450 breast
      cancer cases, were included in the meta-analysis. The dietary intake of beta
      carotene was significantly associated with improved breast cancer OS, with a
      summary hazard ratio of 0.70 (95% confidence interval, 0.50-0.99; I2 = 37.5%) for
      the highest versus lowest intake and 0.93 (95% confidence interval, 0.88-0.99; I2
      = 38.7%) per 1200 MUg/day increment of intake when assessing diet before
      diagnosis. Meta-regression analysis showed that adjustment for body mass index
      was a modified factor for the association between the intake of beta-carotene and
      breast cancer OS (P = .013). However, the intake of other vitamin A derivatives
      (eg, alpha-carotene, beta-cryptoxanthin, lycopene, retinol, lutein) had no effect
      on breast cancer prognosis when assessing diet before and after the diagnosis.
      CONCLUSION: Our findings suggest limited evidence for the significantly inverse
      association between the prediagnosis dietary intake of beta-carotene and OS among
      women with breast cancer. However, the intake of other vitamin A derivatives was
      not significantly associated with survival.

PMID- 30190195
TI  - Including the Ductal Carcinoma-In-Situ (DCIS) Score in the Development of a
      Multivariable Prediction Model for Recurrence After Excision of DCIS.
AB  - INTRODUCTION: Individual prediction of local recurrence (LR) risk after breast
      conserving surgery (BCS) for ductal carcinoma-in-situ (DCIS) is needed to
      identify women at low risk, for whom radiotherapy may be omitted. PATIENTS AND
      METHODS: Three predictive models of LR-clinicopathologic factors (CPF) alone; CPF
      + estrogen receptor (ER) + human epidermal growth factor receptor 2 (HER2); and
      CPF + DCIS score (DS)-were developed among 1102 cases of DCIS in patients with
      complete covariate and outcome data. Categorizations of discrete variables and
      transformations of continuous variables were examined in Cox models; 2-way
      interactions and interactions with time were assessed. Internal validation was
      performed by bootstrapping. Individual predicted 10-year LR risks were computed
      from covariate values, estimated regression parameters, and estimated baseline
      survival function. Accuracy was assessed by c statistics and calibration plots.
      RESULTS: The strongest prediction model incorporated CPF + DS. The c statistics
      for CPF + DS, CPF + ER + HER2, or CPF-alone models were 0.7025, 0.6879, and
      0.6825, respectively. The CPF + DS model was better calibrated at predicting low
      (<= 10%) individual 10-year LR risks after BCS alone than those incorporating CPF
      + ER + HER2 or CPF alone, evidenced by c statistics and plots of observed by
      predicted risks. Among women aged >= 50 with no adverse CPF, the CPF + DS model
      identified the greatest proportion of women (62.3%) with predicted individual 10
      year LR <= 10% without radiotherapy compared to the CPF + ER + HER2 (50.9%) or
      CPF alone (46.5%) models. CONCLUSION: Individual prediction of LR incorporating
      DS is more accurate and identifies a higher proportion of women with low
      predicted risk of LR after BCS alone, for whom radiotherapy may be omitted.

PMID- 30190193
TI  - l-Alanine activates hepatic AMP-activated protein kinase and modulates systemic
      glucose metabolism.
AB  - OBJECTIVE: AMP activated protein kinase (AMPK) is recognized as an important
      nutrient sensor contributing to regulation of cellular, tissue, and systemic
      metabolism. We aimed to identify specific amino acids which could modulate AMPK
      and determine effects on cellular and systemic metabolism. METHODS: We performed
      an unbiased amino acid screen to identify activators of AMPK. Detailed analysis
      of cellular signaling and metabolism was performed in cultured hepatoma cells,
      and in vivo glucose metabolism and metabolomic patterns were assessed in both
      chow-fed mice and mice made obese by high-fat diet feeding. RESULTS: Alanine
      acutely activates AMP kinase in both cultured hepatic cells and in liver from
      mice treated in vivo with Ala. Oral alanine administration improves systemic
      glucose tolerance in both chow and high fat diet fed mice, with reduced efficacy
      of Ala in mice with reduced AMPK activity. Our data indicate that Ala activation
      of AMPK is mediated by intracellular Ala metabolism, which reduces TCA cycle
      metabolites, increases AMP/ATP ratio, and activates NH3 generation. CONCLUSIONS:
      Ala may serve as a distinct amino acid energy sensor, providing a positive signal
      to activate the beneficial AMPK signaling pathway.

PMID- 30190197
TI  - Corrections.

PMID- 30190196
TI  - Quantitative comparison of a laterally misplaced pedicle screw with a re-directed
      screw. How much pull-out strength is lost?
AB  - OBJECTIVE: Redirecting of a laterally misplaced pedicle screw into the accurate
      position decreases the pull-out strength due to the reinsertion, lateral wall
      cortical perforation and widening of the pedicle hole. Thus, this biomechanical
      study was performed to quantitatively analyze the pullout strength of a
      redirected laterally misplaced pedicle screw into the accurate position. METHODS:
      Thirty pedicules of 15 bovine vertebrae were separated to 3 groups, according to
      the screw placement method: 1) standard flawless trajectory; 2) trajectory with
      lateral pedicle wall perforation; 3) trajectory with lateral wall perforation
      redirected to the standard trajectory. Samples were placed on a universal testing
      machine and pullout loads were measured. Kruskal-Wallis test was utilized within
      95% confidence interval and p value <0.05 to test for the statistical
      significance. RESULTS: The mean pullout strength was 2891+/-654,2 N(1383-3814,5)
      in Group 1; 817,8+/-227,6 N(308,6-1144,9) in Group 2 and 2081,1+/-487,7 N(1583,5
      2962,5) in Group 3. The results found out to be statistically significant
      (p<0.05). Inter-group comparisons revealed that lateral pedicle wall perforation
      significantly decreases the pullout strength (p<0.05) and redirection of the
      screw increases the strength (p<0.05), however it was still weaker than the
      screws with flawless standard trajectory but this was not statistically
      significant (p>0.05). CONCLUSION: The results of this study confirm that pullout
      strength of pedicle screw decreases by approximately 71% when the lateral wall is
      perforated and decreases 28% after redirection to the accurate position.

PMID- 30190198
TI  - Are planets lined up for nurses to cross the mirror?
AB  - Since the publication in 2010 of the document 'Nursing in front of the mirror:
      myths and realities', the nursing profession has worked hard to study and
      recognise its myths and realities. Now is the time to ask whether the profession
      is yet in a position to stop standing in front the looking glass and, like Alice,
      cross through.

PMID- 30190199
TI  - Energy self-sufficient biological municipal wastewater reclamation: Present
      status, challenges and solutions forward.
AB  - Almost all present biological processes for treating municipal wastewater have
      been developed based on the philosophy of biological oxidation with high energy
      consumption and generation of waste sludge. Given such a situation, the
      fundamental question of what are the possible ways towards energy self-sufficient
      biological reclamation of municipal wastewater needs to be addressed urgently.
      Therefore, this review aims to offer a critical view and a holistic analysis of
      biological treatment processes with the focus on energy self-sufficiency which
      indeed is a game changer in the future technology development. The way towards
      energy self-sufficient operation of biological processes is to maximize energy
      recovery, while to minimize energy consumption. The examples of such process
      configurations known as A-B processes are thus discussed. Consequently, this
      review may offer in-depth insights into the possible directions towards the next
      generation biological processes for municipal wastewater reclamation which should
      be designed as a water-energy-resource factory.

PMID- 30190200
TI  - Audit of community pharmacists' prescribing interventions: Quality assessment of
      a newly reimbursed service.
AB  - OBJECTIVES: To evaluate community pharmacists' reimbursed prescribing
      interventions (called pharmaceutical opinions/POs in Canada) by determining the
      types of drug-related problems (DRPs) identified; the type, quality, and clinical
      impact of recommendations made; and variation in recommendation quality across
      regions, pharmacy ownership type, and pharmacy size. DESIGN: Retrospective audit
      of randomly sampled service documentation records. SETTING: Community pharmacies
      in Ontario, Canada, 3 years after implementation of a government program that
      reimburses pharmacies for providing DRP-based POs to physicians. PARTICIPANTS:
      Thirty-six community pharmacies in 4 regions of Ontario. MAIN OUTCOME MEASURES:
      For each PO, 2 experienced clinical pharmacists independently, and then by
      consensus, determined the primary drug implicated and its therapeutic category,
      the type of DRP, and the type of prescriber recommendation. Each PO
      recommendation was assessed for clinical impact, evidence base, and overall
      quality. Chi-square analyses assessed the relationship between PO quality and
      pharmacy characteristics. RESULTS: Of 563 POs, 261 (46%) met reimbursement
      criteria for stating a DRP and prescriber recommendation. Among these eligible
      POs, systemic antiinfective (22%), alimentary tract and metabolism (19%), nervous
      system (15%), and cardiovascular (15%) drugs were most commonly identified in the
      DRP. Adverse drug reactions (which included drug interactions) were the most
      common type of DRP (42.5%), followed by "dose too high" (16%) and "needs
      additional therapy" (14%). Top recommendations were to change the drug (41%) and
      to decrease the dose (20%). The quality of the pharmacist's recommendation was
      judged to be good to excellent in 70% of the 261 eligible POs; quality was
      associated with region and ownership type. CONCLUSION: PO quality was suboptimal:
      the primary issue was failure to state a prescriber recommendation. Collaborative
      efforts are needed from community pharmacy stakeholders (schools of pharmacy,
      regulatory colleges, and continuing education providers) to help pharmacists
      enhance the quality of their POs, beginning with their clinical documentation
      skills.

PMID- 30190201
TI  - Pharmacists' experience with prescribing hormonal contraception in Oregon.
AB  - OBJECTIVES: To describe Oregon pharmacy practices in provision of hormonal
      contraception (HC) and evaluate if pharmacists' motivation to prescribe changed
      after 6 and 12 months of experience. METHODS: Pharmacists practicing in Oregon
      who underwent the mandatory HC training were eligible to take this survey. The
      survey was launched 6 months after policy implementation; pharmacists who
      responded to the initial survey were eligible to be queried again at 12 months.
      Survey responses were anonymous, but pharmacists received a unique identifier so
      that responses could be linked between the 2 surveys. The survey consisted of
      pharmacy and pharmacist demographics and questions exploring attitudes toward
      prescribing HC and prescribing practices (e.g., cost, time needed for visit) and
      volume estimates. Descriptive statistics were used to analyze responses as well
      as the differences in key outcomes between 6 and 12 months. RESULTS: A total of
      732 pharmacists were eligible to take the survey; 121 pharmacists responded to
      the 6-month survey (16.5% response rate), and 62 completed the 12-month survey
      (52% response rate). A large increase in the distribution of pharmacists
      prescribing HC by zip code occurred between 6 and 12 months: 19% and 63%,
      respectively. At both 6 and 12 months, almost one-half of all pharmacists were
      billing insurance for the visit, and the average visit took less than 30 minutes.
      The top 3 motivators for providing HC did not change over time and included
      increasing access, reducing unintended pregnancy, and increasing pharmacist scope
      of practice. CONCLUSION: One year after program implementation, pharmacist
      prescribing of HC continues to increase and is distributed widely across the
      state. A geographically diverse sample of Oregon pharmacists began prescribing of
      hormonal contraception within 12 months of Oregon's implementation of the new
      pharmacist provision policy. Their experience and the success of the program
      provide a roadmap for pharmacist participation to increase access to hormonal
      contraception.

PMID- 30190202
TI  - Lung Isolation Techniques in Patients With Early-Stage or Long-Term Tracheostomy:
      A Case Series Report of 70 Cases and Recommendations.
AB  - OBJECTIVES: Lung isolation techniques are designed to facilitate surgical
      exposure in thoracic surgical patients and provide one-lung ventilation (OLV).
      Some patients have a tracheostomy in situ, which makes the management of the
      airway and OLV difficult. The objective of this retrospective study was to review
      cases that had a tracheostomy prior to thoracic surgery and evaluate the clinical
      use and efficiency with the airway management and lung isolation devices. DESIGN:
      This was a retrospective data analysis. SETTING: Tertiary care university
      hospital. INTERVENTIONS: After institutional review board approval, the authors
      reviewed 3,225 charts of patients who had thoracic surgery involving OLV. Seventy
      patients were identified who had tracheostomy in situ. Each case was reviewed
      regarding airway management and lung isolation technique. MEASUREMENTS AND MAIN
      RESULTS: The authors identified 70 patients who had a tracheostomy in situ. The
      cases were divided into 2 groups: a fresh tracheostomy stoma <7 days (n = 6) or
      long-term stoma >7 days (n = 64). The authors collected information regarding the
      devices used to manage the airway and lung isolation techniques. The devices used
      to manage the airway include the Shiley cuffed low pressure tracheostomy tube,
      single-lumen endotracheal tube (SLT), or double-lumen endotracheal tube (DLT).
      Devices used to manage OLV included SLTs, with or without bronchial blockers, or
      DLTs. Flexible fiberoptic bronchoscopy was used to assess the airway and confirm
      the position of the lung isolation device. Six cases had an early-stage fresh
      tracheostomy stoma where the Shiley tracheostomy tube was used for ventilation
      followed by the use of a bronchial blocker. In contrast, for the patients who had
      a long-term stoma, the following devices were used: (1) a SLT plus a bronchial
      blocker in 38 cases, a Shiley tracheostomy tube plus bronchial blocker in 15
      cases, use of a SLT guided into a selective bronchus in 7 cases, and use of a DLT
      in 4 cases. In all cases, flexible fiberoptic bronchoscopy was used and no
      complications occurred secondary to airway management or OLV. CONCLUSION: In
      patients undergoing thoracic surgery and OLV, and with a fresh tracheostomy stoma
      in situ, the authors recommend the use of the Shiley tracheostomy tube plus a
      bronchial blocker. In patients with a long-term tracheostomy stoma, a SLT can be
      used selectively to intubate 1 bronchus. In addition, an SLT or a Shiley tube can
      be used in conjunction with an independent bronchial blocker, such as the Arndt
      wire-guided bronchial blocker, Cohen tip-deflecting blocker, Fuji Uniblocker, or
      EZ-Blocker. DLTs are the least frequently used device for OLV in tracheostomized
      patients.

PMID- 30190203
TI  - A novel somatic CALR mutation in essential thrombocythemia and effective response
      to interferon-alfa-2b therapy.

PMID- 30190204
TI  - Do German public reporting websites provide information that office-based
      physicians consider before referring patients to hospital? A four-step analysis.
AB  - BACKGROUND: In recent years, many different performance frameworks and quality
      assurance systems have been developed to measure health care quality. In Germany,
      an external quality assurance system for hospitals was introduced in 2005. The
      data of these systems are often reported by public reporting websites (PRWs) to
      inform patients and other stakeholders interested in health care systems about
      health care providers' quality. However, publication is obligatory (at least in
      Germany) for most of the existing quality assurance measures; some may be
      reported voluntarily. An important target group for this information is the group
      of all office-based physicians as they are crucial for patients' hospital choice.
      However, public reporting initiatives in Germany and other countries have not
      increased the use of quality reports for hospital choice. OBJECTIVES: (1) To
      summarize the criteria that office-based physicians consider to be of high,
      medium, and low importance for hospital selection when referring patients and (2)
      to examine whether German public reporting websites (PRWs) provide these hospital
      related criteria. METHODS: The analysis comprised four steps: 1) Five databases
      were systematically searched for peer-reviewed English- and German-language
      literature. 2) The selection of articles was based in compliance with inclusion
      criteria, and all the criteria relevant to the referral of patients to hospital
      were extracted. 3) The criteria were then divided into five main categories:
      structural quality, process quality, outcome quality, patient experience, and
      referring physicians' experience. In addition, the criteria were classified into
      three importance categories (high-, medium-, and low-priority criteria) according
      to their relevance to the referral decision. 4) We investigated whether German
      PRWs publicly report high-priority criteria. RESULTS: A total of N=11 articles
      published in peer-reviewed journals met our inclusion criteria. The studies were
      published in Germany (n=4), the Netherlands (n=3), Denmark, France, Norway, and
      the USA (n=1 each). In total, N=86 criteria were identified, most of them
      relating to structural quality (n=43) and process quality (n=26). We found just
      n=3 outcome quality criteria, only one of which fell in the high-priority
      category (breast cancer indicators with clinically relevant differences). In
      total, n=25 low-, n=40 medium-, and n=34 high-priority criteria could be
      established, which is due to the fact that some criteria had been investigated in
      several studies evaluating the importance of some criteria differently. Most of
      the high-priority criteria were related to process quality. All the high-priority
      structural quality criteria and high-priority outcome quality criteria were
      available on German PRWs, whereas just 38.5 % of those relating to process
      quality could be identified on these portals. We also identified 66.7 % of the
      high-priority criteria regarding patient experience and 50.0 % concerning the
      referring physicians' experience. Overall, a larger amount of low- and medium
      priority criteria are available on German PRWs than high-priority criteria.
      DISCUSSION: A substantial amount of hospital information regarding structural
      quality and outcome quality is available on German PRWs. However, the development
      of further process quality criteria (which are currently underrepresented) should
      be considered, for example whether hospital physicians continue the medication
      initiated by office-based doctors. Also, hospital quality reports should be
      tailored for specific user groups, for instance for referring gynecologists or
      referring general practitioners (GPs).

PMID- 30190205
TI  - How far will the FIREHAWK stent fly?

PMID- 30190209
TI  - The role of inflammation and potential pharmacological therapy in intracranial
      aneurysms.
AB  - Intracranial aneurysms remain important clinical concern. There is relatively low
      risk of rupture of symptomless aneurysms incidentally found in MRA or CTA
      performed due to other indications. Not all of the intracranial aneurysms should
      or can be treated with neurosurgery intervention or endovascular embolization.
      Clinical strategy for small, symptomless, unruptured aneurysms is still
      questionable. Mechanisms underlying aneurysms formation, progression and rupture
      are poorly understood. Inflammation is one of the factors suspected to
      participate in these processes. Therefore the aim of this manuscript is to
      present current state of knowledge about the role of inflammation in the
      formation and progression of intracranial aneurysms and in their rupture process.
      Current knowledge about possible pharmacological treatment of intracranial
      aneurysms will also be presented. Macrophages infiltration seems to participate
      in the formation of intracranial aneurysms. Inhibition of signals sent by
      macrophages may prevent the aneurysms formation. Inflammation present in the wall
      of the aneurysm seems to be also related to the aneurysm's rupture risk. However
      it does not seem to be the only cause of the degeneration, but it can be a
      possible target of drug therapy. Some preliminary studies in humans indicate the
      potential role of aspirin as a factor that decrease the level of inflammation and
      lower the risk of rupture of intracranial aneurysms. However further research
      including a greater number of subjects and a prospective randomized design are
      necessary to assess the role of aspirin in preventing strategy for small,
      symptomless, unruptured intracranial aneurysms.

PMID- 30190207
TI  - COX-2-PGE2 Signaling Impairs Intestinal Epithelial Regeneration and Associates
      with TNF Inhibitor Responsiveness in Ulcerative Colitis.
AB  - BACKGROUND: Inhibition of tumor necrosis factor-alpha (TNF) signaling is
      beneficial in the management of ulcerative colitis (UC), but up to one-third of
      patients do not have a clinical response of relevance to TNF inhibitors during
      induction therapy (i.e. primary non-responders [PNRs]). Through production of
      prostaglandins (PGs) and thromboxanes, cyclooxygenase-2 (COX-2) affects
      inflammation and epithelial regeneration and may in this way be implicated in
      treatment resistance to TNF inhibitors. METHODS: In this study, COX-2 expression
      was analyzed in human intestinal biopsies and patient-derived monocytes, and the
      downstream consequences of COX-2 activity was evaluated by assessing the
      influence of the down-stream effector, PGE2, on intestinal epithelial stem cell
      self-renewal and differentiation using primary human intestinal organoids ("mini
      guts"). FINDINGS: We found that TNF stimulation induced COX-2 expression in
      monocytes isolated from responders (Rs), whereas COX-2 expression was
      constitutively high and non-inducible in monocytes from PNRs. Additionally, PGE2
      in combination with proliferative signals transformed human intestinal epithelial
      cells to a proinflammatory state akin to flaring UC, whereas PGE2 in combination
      with differentiation signals supported robust mucin induction. INTERPRETATION:
      Our work indicates that COX-2-PGE2 signaling could be a novel target for the
      management of PNRs to TNF inhibitors. We additionally demonstrate that COX-2-PGE2
      signaling has dual functions during tissue repair and normal lineage
      differentiation, explaining in part the lack of response to TNF inhibitors among
      PNRs. FUND: This work was funded by grants from the Novo Nordisk Foundation, the
      Lundbeck Foundation, the Vanderbilt Digestive Disease Research Center, NIH
      Grants, Aase and Ejnar Danielsen's Foundation and the A.P. Moller Foundation.

PMID- 30190206
TI  - Targeted therapy with a localised abluminal groove, low-dose sirolimus-eluting,
      biodegradable polymer coronary stent (TARGET All Comers): a multicentre, open
      label, randomised non-inferiority trial.
AB  - BACKGROUND: The FIREHAWK is a drug-eluting stent with a fully biodegradable
      sirolimus-containing polymer coating localised to recessed abluminal grooves on
      the stent surface. We investigated clinical outcomes with this targeted, low
      dose, biodegradable polymer, sirolimus-eluting stent compared with XIENCE durable
      polymer, everolimus-eluting stents in an all-comers population. METHODS: The
      TARGET All Comers study was a prospective, multicentre, open-label randomised non
      inferiority trial done at 21 centres in ten European countries. Patients with
      symptomatic or asymptomatic coronary artery disease and objective evidence of
      myocardial ischaemia who qualified for percutaneous coronary intervention were
      randomised 1:1 to undergo implantation of a FIREHAWK or XIENCE. Randomisation was
      web-based, with random block allocation and stratification by centre and ST
      elevation myocardial infarction. Outcome assessors were masked to treatment
      allocation, but treating physicians and patients were not. The primary endpoint
      was target lesion failure at 12 months, a composite of cardiac death, target
      vessel myocardial infarction, or ischaemia-driven target lesion
      revascularisation. The control event rate for XIENCE was assumed to be 7%, the
      non-inferiority margin was 3.5%, and the primary analysis was in the intention-to
      treat population, censoring patients who did not have either an event before 365
      days or contact beyond 365 days. Late lumen loss was the primary endpoint of an
      angiographic substudy designed to investigate the non-inferiority of the FIREHAWK
      compared with the XIENCE stent. This trial is registered with ClinicalTrials.gov,
      number NCT02520180. FINDINGS: From Dec 17, 2015, to Oct 14, 2016, 1653 patients
      were randomly assigned to implantation of the FIREHAWK (n=823) or XIENCE (n=830).
      65 patients in the FIREHAWK group and 66 in the XIENCE group had insufficient
      follow-up data and were excluded from the analyses. At 12 months, target lesion
      failure occurred in 46 (6.1%) of 758 patients in the FIREHAWK group and in 45
      (5.9%) of 764 patients in the XIENCE group (difference 0.2%, 90% CI -1.9 to 2.2,
      pnon-inferiority=0.004, 95% CI -2.2 to 2.6, psuperiority=0.88). There were no
      differences in ischaemia-driven revascularisation or stent thrombosis rates at 12
      months. 176 patients were included in the angiographic substudy, in which in
      stent late lumen loss was 0.17 mm (SD 0.48) in the FIREHAWK group and 0.11 mm
      (0.52) in the XIENCE group (p=0.48), with an absolute difference of 0.05 mm (95%
      CI -0.09 to 0.18, pnon-inferiority=0.024). INTERPRETATION: In a broad all-comers
      population of patients requiring stent implantation for myocardial ischaemia, the
      FIREHAWK was non-inferior to the XIENCE as assessed with the primary endpoint of
      target lesion failure at 12 months and in-stent late lumen loss at 13 months. The
      FIREHAWK is a safe and effective alternative stent to treat patients with
      ischaemic coronary artery disease in clinical practice. FUNDING: Shanghai
      Microport Medical.

PMID- 30190210
TI  - sP- and sE-selectin in stroke patients with metabolic disorders.
AB  - BACKGROUND: Activation of platelets and endothelial cells plays an important role
      in the pathogenesis of atherosclerosis and thrombotic disorders. The aim of our
      study was to assess the relationship between the metabolic disorders and markers
      of platelet activity and vascular injury in patient with acute ischemic stroke.
      MATERIAL AND METHODS: The study group consisted of 84 patients with acute non
      lacunar ischemic stroke divided into four subgroups with: (1) normolipidemia and
      normoglycemia, (2) normolipidemia and hyperglycemia, (3) hyperlipidemia and
      normoglycemia, (4) hyperlipidemia and hyperglycemia. 21 healthy subjects served
      as controls. We analyzed the concentration of adhesion molecules sP-selectin and
      sE-selectin in serum collected from all studied groups using ELISA method.
      RESULTS: We observed significantly higher sE- and sP-selectin concentration in
      patients with hyperglycemia and hyperlipidemia compared to both control subjects
      and patients with normolipidemia and normoglycemia. We did not observe additional
      effect of comorbid hyperlipidemia and hyperglycemia on studied markers. Soluble E
      and P-selectin concentration correlated positively with LDL, TC and HbA1c level
      in all stroke patients. CONCLUSION: Soluble E- and P-selectin, blood markers of
      vascular injury and platelet activation, could be useful in the assessment of
      atherothrombotic properties of hyperglycemia and hyperlipidemia in stroke
      patients.

PMID- 30190208
TI  - Hepatitis E virus infection in acute non-traumatic neuropathy: A large
      prospective case-control study in China.
AB  - Neurological manifestations are potentially associated with hepatitis E virus
      (HEV) infection in Europe, mainly attributed to genotype (GT) 3 HEV infection. In
      this study, we determined the frequency and causal relationship of HEV in
      patients with non-traumatic neurological disorders in China, where GT4 HEV is
      prevalent. 1117 consecutive patients diagnosed with neurological illnesses in a
      hospital of eastern China and 1475 healthy controls who took routine examination
      in the same hospital were tested for HEV by serology and molecular methods. Anti
      HEV IgM antibodies were detectable in 6 (0.54%) of the patients and 10 (0.68%) of
      the healthy controls (P = 0.651). Serum HEV RNA was detected in all of the 16
      individuals with positive anti-HEV IgM. The six patients with HEV infection
      included two viral encephalitis, two posterior circulation ischemia, one
      peripheral neuropathy and one Guillian-Barre syndrome. They had no symptoms of
      acute viral hepatitis except two patients of viral encephalitis that showed
      mildly transaminitis. Additional, 39.51% patients and 35.63% controls without
      acute HEV infection were positive for anti-HEV IgG (P = 0.144). Anti-HEV IgG
      positivity was more frequent in male and elderly in both the patients and control
      groups, but unrelated to the incidence of any non-traumatic neurological illness,
      hospital stay or treatment outcome, except linking to better outcome of
      hemorrhagic stroke disease. These data demonstrated that HEV appears not to
      contribute to acute neurological disorders in China. Nevertheless, we cannot
      exclude a possible causative role, suggesting that testing HEV in this
      population, especially in situations of unexplained deregulated liver function
      would be warranted.

PMID- 30190211
TI  - Lymphocyte populations and their change during five-year glatiramer acetate
      treatment.
AB  - BACKGROUND: The goal of this study was to determine the characteristics that are
      affected in patients treated with glatiramer acetate (GA). METHODS: A total of
      113 patients were included in this study. Patients were treated with glatiramer
      acetate (subcutaneous injection, 20 mg, each day). Peripheral blood samples were
      obtained just prior to treatment as well as 5 years after GA treatment. All the
      calculations were performed with the statistical system R (r-project.org).
      RESULTS: After 5 years of treatment, a significant decrease was found in the
      absolute and relative CD3+/CD69+ counts, the absolute and relative CD69 counts,
      the relative CD8+/CD38+ count and the relative CD38 count. A significant increase
      was found in the absolute and relative CD5+/CD45RA+ counts and the absolute
      CD5+/CD45RO+ count after 5 years of treatment. CONCLUSION: This study presents
      some parameters that were affected by long-term GA treatment.

PMID- 30190213
TI  - Clinimetrics: The Wheelchair User's Shoulder Pain Index (WUSPI).

PMID- 30190214
TI  - Critically appraised paper: Long-term, individualised physical activity and
      exercise coaching does not improve maintenance of motor function after stroke
      [synopsis].

PMID- 30190212
TI  - Case series of trigonal meningiomas.
AB  - BACKGROUND: Trigonal meningiomas have unique clinical presentation, unlike those
      in other areas of brain. Situated deep in the brain, the surgical nuances of this
      tumour are distinctive. We present our experience with this tumour including a
      discussion of surgical corridors that may be employed. METHODS: At our centre, 12
      trigonal meningiomas were operated over past two decades. A retrospective
      analysis of case records of these cases was undertaken as regards age, sex
      clinical presentation, imaging and surgical approach. RESULTS: Mean time from
      heralding symptom to presentation was 10.4 months. At presentation, the most
      commonly encountered symptoms were those of non-localising symptoms attributable
      to raised ICP. Majority of lesions were more than 6 cm and on left side and the
      preferred surgical approach was inferior temporo-parietal. Most symptoms were
      relieved on long-term follow-up except homonymous hemianopia. CONCLUSION: The
      incidence of deficit is low on employing the "shortest route" approach, even in
      the dominant hemisphere and through eloquent area. This may be secondary to
      possible shift of eloquent area function due to longstanding lesion and may thus
      be a "workable" surgical option, especially in resource-limited centres where
      such resources as neuronavigation and tractography may be unavailable.

PMID- 30190215
TI  - Media: Review - Pulmonary Rehabilitation Toolkit: a physiotherapist's
      perspective.

PMID- 30190216
TI  - Appraisal of Clinical Practice Guideline: Knee Stability and Movement
      Coordination Impairments: Knee Ligament Sprain.

PMID- 30190217
TI  - Critically appraised paper: Workplace physical exercise reduces musculoskeletal
      pain among healthcare workers more than home-based exercise [synopsis].

PMID- 30190218
TI  - Research Note: The smallest worthwhile effect of a health intervention.

PMID- 30190219
TI  - Appraisal of Clinical Practice Guideline: COPD-X Australian and New Zealand
      guidelines for the diagnosis and management of chronic obstructive pulmonary
      disease: 2017 update.

PMID- 30190220
TI  - Behavioral disorders and impairment of quality of life in children and
      adolescents with lower urinary tract dysfunction.
AB  - BACKGROUND: Lower urinary tract dysfunction (LUTD) is a broad term describing the
      full spectrum of disorders in any of the stages of bladder function-storage or
      voiding LUTD is a clinical condition associated with emotional and behavioral
      disorders in children. This cross-sectional study aimed to investigate the
      association of emotional and behavioral symptoms and their impact on the quality
      of life (QoL) in children and adolescents with LUTD. METHODS: Eighty-eight
      patients and their parents enrolled in an interdisciplinary program for children
      and adolescents with LUTD were included in the analysis. Child Behavior Checklist
      (CBCL) was used to estimate the prevalence of behavioral and emotional problems
      through the assessment of 14 items. Pediatric Quality of Life Inventory (versions
      for parents and children) was applied in the versions for parents and children to
      evaluate the QoL. The Pediatric Quality of Life Inventory-PedsQL, version 4.0-was
      applied separately for parents and patients. The association of clinical
      variables and aspects related to QoL of patients were evaluated through non
      parametric correlations (Spearman) and multiple linear regression analysis.
      RESULTS: According to CBCL's clinical scores, 56% of the patients showed total
      behavioral problems, 55% internalizing, and 38% externalizing. When comparing the
      conditions of LUTD and the CBCL scores, patients with voiding postponement had
      the lowest rates of total problems (P = 0.036). Children and adolescents with
      LUTD who also had enuresis showed a higher frequency of externalizing problems (P
      = 0.001), especially aggressive behavior (P = 0.013). Scores of patients with
      LUTD were significantly lower in all domains of QoL than normative data. Presence
      of behavioral problems was associated with worse QoL in all evaluated aspects.
      The total QoL was most influenced by the CBCL school competence scale according
      to the regression model analysis. CONCLUSIONS: The study findings suggest the
      relevance of evaluation of behavioral and social repercussions of LUTD to improve
      the multidisciplinary approach for this condition in pediatric population.

PMID- 30190221
TI  - Incidence and Method of Suicide in Hospitals in the United States.
AB  - BACKGROUND: There are no reliable estimates of hospital inpatient suicides in the
      United States. Understanding the rate and the methods used in suicides is
      important to guide prevention efforts. This study analyzed two national data sets
      to establish an evidence-based estimate of hospital inpatient suicides and the
      methods used. METHODS: The study is designed as a cross-sectional analysis of
      data from 27 states reporting to the National Violent Death Reporting System
      (NVDRS) for 2014-2015, and from hospitals reporting to The Joint Commission's
      Sentinel Event (SE) Database from 2010 to 2017. Categorical variables and
      qualitative reviews of event narratives were used to identify and code suicide
      events occurring during hospital inpatient treatment. RESULTS: Based on the
      hospital inpatient suicides reported in the NVDRS during 2014-2015, 73.9% of
      which occurred during psychiatric treatment, it is estimated that between 48.5
      and 64.9 hospital inpatient suicides occur per year in the United States. Of
      these, 31.0 to 51.7 are expected to involve psychiatric inpatients. Hanging was
      the most common method of inpatient suicide in both the NVDRS and SE databases
      (71.7% and 70.3%, respectively). CONCLUSION: The estimated number of hospital
      inpatient suicides per year in the United States ranges from 48.5 to 64.9, which
      is far below the widely cited figure of 1,500 per year. Analysis of inpatient
      suicide methods suggests that hospital prevention efforts should be primarily
      focused on mitigating risks associated with hanging, and additional suicide
      prevention efforts may be best directed toward reducing the risk of suicide
      immediately following discharge.

PMID- 30190222
TI  - Evaluating the Current Place of Radiotherapy as Treatment Option for Patients
      With Muscle Invasive Bladder Cancer in Belgium.
AB  - INTRODUCTION: There is a gap between optimal and actual use of radiotherapy (RT)
      in muscle-invasive bladder cancer (MIBC). We investigated the opinions of
      radiation-oncologists, urologists, and medical oncologists on use of RT in
      different cases. Barriers and facilitators for applying guidelines were examined.
      MATERIAL AND METHODS: A web-based survey was developed at Ghent University
      Hospital and conducted from November 18, 2016 to July 17, 2017. The place of
      primary, adjuvant, and palliative RT was evaluated. Additional questions assessed
      the use of guidelines, barriers, and facilitators. RESULTS: In total, 126
      physicians (57 radiation oncologists, 41 urologists, and 28 medical oncologists)
      completed the survey. Significant differences in use of RT in the primary and
      adjuvant setting were observed between radiation oncologists and urologists.
      Younger age and presence of hydronephrosis are perceived as contraindications for
      RT in the primary setting. In the adjuvant setting, RT was mainly considered in
      case of positive surgical margins. All radiation oncologists and 96% of medical
      oncologists considered palliative RT for patients with painful bone metastases,
      whereas 21% of urologists did not (P < .001). Clinical decisions are mainly based
      on EAU guidelines. The most important reason for nonadherence to guidelines is
      external barriers (18%). One strategy to improve awareness of guidelines is a
      summary of guidelines on the website of national organizations (54%). CONCLUSION:
      There is controversy regarding the place of RT in MIBC, with a clear variation
      between professionals. Barriers and facilitators to use RT should be addressed,
      seeing the gap in RT utilization and predicted increase in patients requiring RT
      for MIBC.

PMID- 30190223
TI  - Specialist ambulance nurses' experiences of births before arrival.
AB  - BACKGROUND: Working as an ambulance nurse means interacting with and caring for
      acutely ill and injured patients. It can even involve births before arrival to
      the hospital (BBA), which are rare but increasing due to the centralization of
      maternity wards. AIM: This study describes the experiences of specialist
      ambulance nurses with BBA. METHOD: A qualitative study was conducted, and nine
      specialist ambulance nurses who had assisted with one or more prehospital births
      were interviewed. Data were analysed with thematic content analysis. FINDINGS:
      The analysis revealed three categories that were compiled into a theme of feeling
      fright and exhilaration. The findings showed that BBA causes feelings of anxiety
      and stress. The experience is also associated with joy and relief when the baby
      is born. Childbirth is a situation for which specialist ambulance nurses feel
      less prepared, lack of knowledge, and wish for more education. CONCLUSION:
      Specialist ambulance nurses face challenges in the pre-hospital care environment
      during BBA, with long distances, a lack of equipment aboard the ambulance, and no
      assistance from midwives. To feel secure in the complex role that is required
      when assisting with a BBA, specialist ambulance nurses should be given the
      opportunity to receive scenario training.

PMID- 30190224
TI  - Significant changes in emergency department length of stay and case mix over
      eight years at a large Swedish University Hospital.
AB  - OBJECTIVE: Describe the longitudinal development of crowding and
      patient/emergency department (ED) characteristics at a Swedish University
      Hospital. METHODS: A retrospective longitudinal registry study based on all ED
      visits with adult patients during 2009-2016 (N = 1,063,806). Patient
      characteristics and measures of ED crowding (ED occupancy ratio, length-of-stay
      [LOS], patients/clinician's ratios) were extracted from the hospital's electronic
      health record. Non-parametric analyses were conducted. RESULTS: The proportion of
      unstable patients (triage level 1-2) increased while the proportion of admitted
      patients decreased. All crowding variables were stable, except for LOS, which
      increased by 9 min/visit/year (95% CI: 8.8-9.1). LOS for visits by patients >= 80
      years increased more compared to those 18-79 (248 min vs. 190 min, p < 0.001).
      Unstable patients increased their median LOS compared to stable patients (triage
      level 3-5). LOS for discharged patients increased with an average of 7.7 min/year
      (95% CI: 7.5-7.9) compared to 15.5 min/year (95% CI: 15.2-15.8) for those being
      admitted. CONCLUSION: Fewer admissions, despite an increase of unstable patients,
      is likely related to lack of in-hospital beds and contributes to ED crowding. The
      increase in median ED LOS, especially for patients in the subgroups unstable,
      >=80 years and admitted to in-hospital care reflects this problem.

PMID- 30190225
TI  - Combined Pulmonary Fibrosis and Emphysema Versus Idiopathic Pulmonary Fibrosis
      Versus Emphysema: A Clinical Perspective.

PMID- 30190226
TI  - Vena Cava Filter Complications.

PMID- 30190227
TI  - Admission in Neurorehabilitation and Association with Functional Outcomes after
      Stroke in France: A Nation-Wide Study, 2010-2014.
AB  - GOAL: We studied time trends of admission in neurological rehabilitation units
      (NRU) among patients hospitalised for stroke from 2010 to 2014 and compared
      prognostic factors of functional gain, home return and inpatient survival.
      METHODS: Patients hospitalized for Stroke from 2010 to 2014 were selected from
      the French national hospital databases. Admission in rehabilitation was searched
      till 3 months. Predictive factors of functional gain, home return, in-patient
      survival, and the corresponding trends were studied using logistic regression.
      RESULTS: In 2014, global rehabilitation rate was 36.3% with 15.8 discharged in a
      NRU. The rate of patients managed in NRU rose between 2010 and 2014. An increase
      in the proportion of home return (+4%) and inpatient survival rate (+7%) were
      observed between 2010 and 2014. Almost 40% of patients with severe functional
      deficits benefited of a partial or complete recovery after their rehabilitation
      stay. NRU admission was associated with higher probability of functional gain (OR
      [odds ratio] =1.76 [confidence interval {CI} 95% 1.67-1.85]), home return (OR =
      1.38 [CI 95% 1.29-1.47]) and inpatient survival (OR = 3.15 [CI 95% 2.83-3.52]).
      CONCLUSIONS: A greater proportion of patients were admitted in NRU along with an
      increase of home return and in-patient survival, but too many patients remained
      excluded.

PMID- 30190228
TI  - Perception's Crucial Role in Radiology Education.

PMID- 30190229
TI  - How Evolutionary Theory Illuminates Radiologic Practice: Bipedalism.

PMID- 30190230
TI  - When designing vaccines, consider the starting material: the human B cell
      repertoire.
AB  - Most viral vaccines provide protection from infection through the generation of
      neutralizing antibodies (nAbs). The repertoire of B cells responding to
      immunization is the starting material from which nAbs eventually arise.
      Immunization strategies are increasingly targeting precise B cell specificities
      to mimic nAbs generated during natural infection, in an effort to maximize the
      potency of the vaccine-elicited Ab response. An understanding of the human B cell
      specificities capable of immunogen recognition can aid in immunogen design and
      inform decision-making for clinical advancement. Here, we review what is known
      about antigen-specific and epitope-specific naive B cell repertoires in humans
      and mice, and we consider the challenges for identifying and analyzing antigen
      specific naive B cell repertoires. Finally, we provide a framework for further
      exploration, interpretation, utilization of the B cell repertoire to facilitate
      vaccine discovery.

PMID- 30190232
TI  - C-reactive protein levels can predict positive 18F-FDG PET/CT findings that lead
      to management changes in patients with bacteremia.
AB  - BACKGROUND/PURPOSE: Bacteremia portends high rates of morbidity and mortality.
      Although 18F-fluorodeoxyglucose positron emission tomography and computed
      tomography (18F-FDG PET/CT) imaging has clinical value in assessing fever of
      unknown origin, its usefulness in bacteremia has not been entirely elucidated. We
      therefore designed the current single-center retrospective study to investigate
      1) the clinical value of 18F-FDG PET/CT imaging in assessing bacteremia and 2)
      the association between laboratory data and imaging findings. METHODS: We
      examined 102 patients with bacteremia who had undergone 18F-FDG PET/CT imaging.
      The patients' clinical and laboratory data were reviewed and analyzed in relation
      to 18F-FDG PET/CT findings. Patients showing positive results underwent
      quantitative measurements of 18F-FDG uptake. RESULTS: Positive 18F-FDG PET/CT
      findings were identified in 74 (72.5%) patients, and 40 (54.1%) underwent
      modified treatment or management because of the imaging results (p = 0.003).
      Positive 18F-FDG PET/CT findings were significantly associated with higher white
      blood cell (WBC) counts and C-reactive protein (CRP) levels (p = 0.012 and <
      0.001, respectively). Notably, CRP levels accurately predicted (area under curve
      = 0.752; p < 0.001) positive 18F-FDG PET/CT findings (optimal cut-off point:
      54.025 mg/L). CONCLUSION: A majority (54.1%, n = 40) of the patients with
      positive 18F-FDG PET/CT results underwent treatment modifications; they accounted
      for most cases (87%) of management changes in our cohort. Leukocytosis and
      increased CRP levels are significantly associated with positive 18F-FDG PET/CT
      findings in patients with bacteremia. CRP levels >54.025 mg/L were accurate
      predictors of positive 18F-FDG PET/CT results.

PMID- 30190233
TI  - Enterobius vermicularis infection mimicking strongyloidiasis: A case report.

PMID- 30190231
TI  - Biopiracy versus One-World Medicine-From colonial relicts to global collaborative
      concepts.
AB  - BACKGROUND: Practices of biopiracy to use genetic resources and indigenous
      knowledge by Western companies without benefit-sharing of those, who generated
      the traditional knowledge, can be understood as form of neocolonialism.
      HYPOTHESIS: The One-World Medicine concept attempts to merge the best of
      traditional medicine from developing countries and conventional Western medicine
      for the sake of patients around the globe. STUDY DESIGN: Based on literature
      searches in several databases, a concept paper has been written. Legislative
      initiatives of the United Nations culminated in the Nagoya protocol aim to
      protect traditional knowledge and regulate benefit-sharing with indigenous
      communities. The European community adopted the Nagoya protocol, and the
      corresponding regulations will be implemented into national legislation among the
      member states. Despite pleasing progress, infrastructural problems of the health
      care systems in developing countries still remain. Current approaches to secure
      primary health care offer only fragmentary solutions at best. Conventional
      medicine from industrialized countries cannot be afforded by the impoverished
      population in the Third World. Confronted with exploding costs, even health
      systems in Western countries are endangered to burst. Complementary and
      alternative medicine (CAM) is popular among the general public in industrialized
      countries, although the efficacy is not sufficiently proven according to the
      standards of evidence-based medicine. CAM is often available without prescription
      as over-the-counter products with non-calculated risks concerning erroneous self
      medication and safety/toxicity issues. The concept of integrative medicine
      attempts to combine holistic CAM approaches with evidence-based principles of
      conventional medicine. CONCLUSION: To realize the concept of One-World Medicine,
      a number of standards have to be set to assure safety, efficacy and applicability
      of traditional medicine, e.g. sustainable production and quality control of
      herbal products, performance of placebo-controlled, double-blind, randomized
      clinical trials, phytovigilance, as well as education of health professionals and
      patients.

PMID- 30190234
TI  - A comparison of safety and outcomes with cefazolin versus nafcillin for
      methicillin-susceptible Staphylococcus aureus bloodstream infections.
AB  - BACKGROUND: Methicillin-susceptible Staphylococcus aureus (MSSA) is a frequent
      cause of bloodstream infections (BSI). Treatment with nafcillin (NAF) has been
      preferred to cefazolin (CFZ). However, comparable outcomes have been found with
      CFZ with possibly lower risk for side-effects. This study compared safety and
      effectiveness of NAF versus CFZ for MSSA BSI. METHODS: This single center
      retrospective study evaluated adults admitted with MSSA BSI who received NAF or
      CFZ. Patients receiving >=24 h of antibiotics were included for safety analyses.
      Patients receiving NAF or CFZ for >=75% of a 14 day minimum treatment course were
      assessed for clinical effectiveness. The primary safety outcome was incidence of
      renal toxicity with multiple secondary safety endpoints. Clinical success was
      defined as symptom resolution, repeat negative cultures, lack of additional
      therapy for presumed failure, and lack of recurrence within 30 days. RESULTS: A
      total of 130 patients receiving NAF (n = 79) or CFZ (n = 51) were included for
      safety analysis. Of those, 90 met criteria for effectiveness assessment (NAF n =
      40, CFZ n = 50). Baseline characteristics were well matched. NAF was associated
      with a higher incidence of nephrotoxicity compared to CFZ (25% vs. 2%, RR 1.31,
      95% CI 1.15-1.5, p < 0.001), allergic reactions (p = 0.01) and a trend for
      hepatotoxicity (p = 0.08). Clinical success was achieved in 82% NAF and 94% CFZ
      treated patients (p = 0.1). CONCLUSION: CFZ was associated with less
      nephrotoxicity and no difference in clinical success compared to NAF for MSSA
      BSI. A prospective study comparing NAF to CFZ for MSSA BSI should be conducted to
      elucidate differences in therapies.

PMID- 30190235
TI  - R-loop generation during transcription: Formation, processing and cellular
      outcomes.
AB  - R-loops are structures consisting of an RNA-DNA duplex and an unpaired DNA
      strand. They can form during transcription upon nascent RNA "threadback" invasion
      into the DNA duplex to displace the non-template strand. Although R-loops occur
      naturally in all kingdoms of life and serve regulatory roles, they are often
      deleterious and can cause genomic instability. Of particular importance are the
      disastrous consequences when replication forks or transcription complexes collide
      with R-loops. The appropriate processing of R-loops is essential to avoid a
      number of human neurodegenerative and other clinical disorders. We provide a
      perspective on mechanistic aspects of R-loop formation and their resolution
      learned from studies in model systems. This should contribute to improved
      understanding of R-loop biological functions and enable their practical
      applications. We propose the novel employment of artificially-generated stable R
      loops to selectively inactivate tumor cells.

PMID- 30190236
TI  - Can imaging distinguish between low-grade and dedifferentiated parosteal
      osteosarcoma?
AB  - BACKGROUND: Most instances of the parosteal osteosarcoma (OGS) are low-grade
      tumors. However, some parosteal OGSs undergo dedifferentiated transformation.
      Dedifferentiated parosteal OGS can cause distant metastasis and poor survival,
      and preoperative chemotherapy may be warranted. This study provides imaging clues
      for dedifferentiated parosteal OGS before treatment. METHODS: The study
      retrospectively enrolled 23 patients with histologically proven parosteal OGS,
      including 69.6% (n = 16) low-grade and 30.4% (n = 7) dedifferentiated types.
      Preoperative images including radiography and magnetic resonance imaging were
      reviewed. The following imaging parameters and clinical outcomes were evaluated:
      1) average age; 2) sex; 3) tumor size; 4) presence of string sign; 5) necrosis;
      6) hemorrhage; 7) solid soft tissue component; 8) perforating vessels; 9)
      ossification grade; 10) marginal ossification; 11) periosteal reaction; 12)
      sunburst reaction; 13) bone marrow edema; 14) bone marrow invasion; 15) perifocal
      soft tissue edema; 16) adjacent joint involvement; 17) adjacent neurovascular
      bundle compression; 18) regional lymph node; 19) bone metastasis; 20)
      preoperative lung metastasis; 21) follow-up lung metastasis; and 22) recurrence.
      RESULTS: The average maximal tumor sizes were 7.1 cm and 10.9 cm in low-grade and
      dedifferentiated types, respectively (p = 0.033). Sunburst periosteal reaction
      was visualized in two cases of low-grade type (12.5%) and four cases of the
      dedifferentiated type (57.1%) (p = 0.025) of parosteal OGS. None of our studied
      cases revealed preoperative lung metastasis. In the follow-up chest computed
      tomography, lung metastasis was noted in two cases of conventional type (14.2%),
      and four cases of dedifferentiated type (57.1%) (p = 0.040) of parosteal OGS. In
      receiver operating characteristic (ROC) curve analysis, the average tumor size
      and sunburst periosteal reaction showed good specificity (AUC = 0.070 and 0.072,
      respectively). CONCLUSION: Compared with low-grade types, dedifferentiated
      parosteal OGS exhibits a considerably larger tumor size, more sunburst periosteal
      reaction, and a more frequent development of lung metastasis in the disease
      course. Tumor size and sunburst periosteal reaction are the most crucial imaging
      diagnostic factors.

PMID- 30190237
TI  - Corrigendum to "Reflections on the usefulness of extracorporeal photopheresis in
      renal transplant rejection: A concise review of the involved mechanisms and
      therapeutic perspectives" [Transfus. Apher. Sci. 57 (February (1)) (2018) 115
      117].

PMID- 30190238
TI  - Corrigendum to "Structure and evolution of the stigmapophysis - A unique repose
      wing-coupling structure in Psocodea" [Arthropod Structure & Development, 47 (4)
      (2018) 416-422].

PMID- 30190239
TI  - Clinical characteristics of elderly drowning patients.
AB  - PURPOSE: Drowning is one of the major causes of traumatic death. The impact of
      drowning in the elderly and patients who were not elderly will be different
      because of physiological differences. We wanted to analyze the clinical
      differences such as mortality, incidence rate of complications, degree of
      hypothermia and rate of cardiac arrest between elderly and adult drowning
      patients. METHODS: This study included drowning patients over 18 years old who
      came to an emergency department (ED) located on a riverside from September 1997
      to July 2016. Patients over the age of 65 years were classified as elderly, while
      those under the age of 65 years were classified as adults. Demographic data and
      clinical outcomes were surveyed. RESULTS: A total of 611 patients were included
      in this study. Sixty-one patients (9.9%) were elderly, and 550 patients (90.1%)
      were adults. There were 17 elderly patients (15.8%) and 87 adult patients (27.9%)
      who had cardiac arrest at the time of ED arrival (p = 0.017). The rate of body
      temperatures < 34  degrees C was higher in elderly patients than that in adult
      patients (27.9% vs 17.5%, respectively, p = 0.025). The rates of hospitalization
      in the intensive care unit (ICU) and mortality were higher in elderly group (23%
      vs. 15.1%, respectively, p = 0.01; 37.7% vs 21.8%, respectively, p = 0.01). There
      was no significant difference in suicidal intent between the elderly and adult
      patient groups (82.0% vs 78.9%, respectively, p = 0.421). CONCLUSIONS: Elderly
      drowning patients accounted for approximately 1/10 of all drowning cases and were
      more likely to experience a cardiac arrest, hypothermia, mortality, and ICU
      admission.

PMID- 30190241
TI  - Geographic variation in predictors of emergency department admission rates in
      U.S. Medicare fee-for-service beneficiaries.
AB  - INTRODUCTION: We study community-level factors associated with emergency
      department (ED) admission rates and assessed how they vary across geography.
      METHODS: We conducted an ecological study using 2012 data from 100% of U.S.
      Medicare Fee-for-Service beneficiaries to calculate county-level ED admission
      rates, adjusted by Hierarchical Condition Categories to control for patient
      health. We tested community-level measures related to healthcare market
      concentration, healthcare delivery, and socioeconomic factors potentially
      associated with admission rates and assessed whether these factors predicted ED
      admission rates across counties using ordinary least squares (OLS) regression and
      whether they varied across geography using geographically weighted regression
      (GWR). RESULTS: In 3031 U.S. counties, the ED admission rate varied from 3.9% to
      82.2%. The lowest ED admission rates were concentrated in counties in Kansas,
      Oregon, and Vermont and the highest ED admission rates were in counties
      throughout Washington, Wyoming, Texas, and Colorado. The OLS model found several
      community-level factors that negatively impacted admission rates, specifically
      hospital market concentration, the rate of hospital beds with urgent care, and
      the rate of hospital beds. The factors that had a positive impact on the
      admission rate include the rate of MDs and factors for disadvantage, affluence,
      and foreign born/Hispanic. However, GWR showed the relationship between the ED
      admission rate and predictors varied across U.S. counties CONCLUSIONS: The
      association between healthcare market concentration, healthcare delivery, and
      socioeconomic factors with ED admissions differed across communities in Medicare
      beneficiaries. This suggests that policy and interventions to reduce ED
      admissions need to be tailored to specific community contexts.

PMID- 30190240
TI  - Reducing mortality in near-hanging patients with a novel early management
      protocol.
AB  - BACKGROUND: Hanging is one of the most common causes of suicide world-wide, more
      prevalent in developing countries. There are no established protocols for early
      management of near-hanging patients who present to the emergency department (ED).
      The use of early intubation, strict blood pressure control and targeted
      temperature management has shown promise in small studies. OBJECTIVE: To detect
      changes in mortality and neurological deficits in near-hanging patients before
      and after implementation of a novel early management protocol in a tertiary care
      hospital in India. METHODS: Prospective cohort study conducted at a tertiary-care
      hospital in Tamil Nadu, India from August 2014-July 2016. For first year of study
      (pre-implementation), near-hanging patients were treated without a structured
      protocol. For second year of study (post-implementation), near-hanging patients
      were treated per a protocol including early intubation, strict blood pressure
      control and targeted temperature management. Primary outcomes included: (1) in
      hospital mortality and (2) hospital discharge without neurological deficit.
      RESULTS: 65 patients were included (27 in the pre-implementation phase and 38 in
      the post-implementation phase.) At presentation, there was no difference between
      the two groups in mean heart rate, mean arterial pressure, mean oxygen
      saturation, Glasgow coma score, or mean respiratory rate. Protocol implementation
      decreased mortality (10/27 (37%) versus 2/38 (5%), P < 0.05) and increased the
      number of patients discharged without neurological deficit (10/27 (37%) versus
      35/38 (92%), P < 0.05). CONCLUSIONS: This novel early management protocol reduced
      mortality and increased the number discharged without neurological deficit in
      near-hanging patients in a single tertiary care center in India.

PMID- 30190243
TI  - A leadership-based program can reduce boarding time of emergency department
      admissions.

PMID- 30190242
TI  - First-presentation with psychotic behavior to the Emergency Department:
      Meningitis or not, that is the question.
AB  - INTRODUCTION: Meningitis is a potentially life threatening medical emergency.
      Psychotic behavior may be a presenting feature in patients with meningitis. We
      aimed to determine the value of various clinical and laboratory features at
      ruling-out meningitis in the patient presenting with a first-episode of psychotic
      behavior. METHODS: Medical records of 159 subjects presenting to a tertiary
      academic hospital over a 6-month period with one or more psychotic features for
      the first time were prospectively gathered. Pathological cerebrospinal fluid
      findings as well as clinical and other laboratory findings were tabulated and
      discussed retrospectively. RESULTS: Cerebrospinal fluid was obtained in 153/159
      (96.2%) subjects. Meningitis was confirmed in twenty-eight (18.3%) subjects. Of
      these, a) one or more clinical feature of meningitis (headache, neck stiffness,
      photophobia or focal neuropathy) was present in 21 subjects (75.0%), b) visual
      hallucinations in 15 subjects (53.6%), c) pyrexia >37.5  degrees C in 7 subjects
      (25.0%), d) CRP >10 mg/L in 21 subjects (75.0%), e) HIV seropositive status in 19
      subjects (67.9%) and f) an absence of illicit substances on urinalysis in 23
      subjects (82.1%). Various combinations of these variables, where the presence of
      >=1 variable was regarded as positive, were unable to rule-out meningitis in all
      study subjects. CONCLUSION: The absence of these six parameters; alone or in
      various combinations, was unable to rule-out meningitis in all patients
      presenting to our ED with a first-episode of psychotic behavior. When the
      underlying etiology of psychotic behavior is not obvious, the clinician should
      adopt a low threshold to perform a lumbar puncture.

PMID- 30190245
TI  - Peria-ortic Adipose Tissue is More than Plain Fat.

PMID- 30190244
TI  - Fasting glucose in the first trimester: An initial approach to diagnosis of
      gestational diabetes.
AB  - OBJECTIVES: To establish whether fasting glucose levels in the first trimester
      (FGFT)of pregnancy >= 92 mg/dL (5.1 mmol/L) (FGFT) anticipate the occurrence of
      maternal-fetal complications of gestational diabetes mellitus. To assess whether
      FGFT can replace diagnosis of GDM using the classical two-step oral glucose
      tolerance test (OGTT). METHODS: A retrospective study of 1425 pregnancies with
      FGFT and O'Sullivan Test (OST) and/or OGTT according to OST results in the second
      trimester. FGFT sensitivity and specificity were assessed as compared to the
      conventional diagnosis of GDM. The relationship between maternal-fetal
      complications and FGFT was assessed in the total group and after excluding
      mothers who received specific medical treatment for GDM. RESULTS: Sensitivity and
      specificity of FGFT levels >= 92mg/dL were 46.4% and 88.8% as compared to
      diagnosis of GDM using Carpenter and Coustan criteria. In the total group, a
      statistically significant relationship was found between FGFT levels >= 92 mg/dL
      and newborn weight (3228+/-86 versus 3123+/-31g; P<.05), as well as a higher rate
      of macrosomia (6.9% versus 3.5%; P<.05). This association persisted after
      excluding patients diagnosed with and treated for GDM (weight: 3235+/-98 versus
      3128+/-31 g; P<.05; percentage of macrosomia: 7.2% versus 3.4%; P<.05).
      CONCLUSIONS: FGFT is not a good substitute for conventional diagnosis of GDM in
      the second trimester. Pregnant women with FGFT levels >= 92 mg/dL, even with no
      subsequent diagnosis of GDM, are a risk group for fetal macrosomia and could
      benefit from dietary measures and physical exercise.

PMID- 30190247
TI  - Variability in the nurse-patient ratio in neonatal intensive care units and
      intermediate care units.

PMID- 30190246
TI  - Technical refinements to a validated autologous fat harvesting technique.

PMID- 30190248
TI  - Nursing records, prevention measures and incidence of pressure ulcers in an
      Intensive Care Unit.
AB  - OBJECTIVES: The aim of this paper is to determine the incidence and most incident
      pressure ulcers (PU) category. Establish the main clinical characteristics of
      these PU. Determine whether there is adequate documentation of PU and of the
      measures used to prevent them. METHOD: Observational descriptive and
      retrospective study during 2014 at Intensive Care Unit (ICU)-University Hospital
      of Araba. Study sample, all patients suffering from PU at the time of the study
      by accidental sampling. Computerised records regarding risk assessment, clinical
      assessment and pressure sore treatment, provided by the 'Metavision' computer
      programme and descriptive statistics using SPSS version 22.0. Approval from the
      Ethics Committee for Clinical Research of the University Hospital of Araba was
      obtained. RESULTS: The incidence of patients suffering from PU during 2014 was
      6.78%. The most common locations for PU were the sacral region and the heels: the
      most incident pressure ulcers category was grade II, followed by grade I. Out of
      the 98 PU treated in our patients, 43 occurred outside the ICU and 55 in the unit
      itself. The lack of records, in all the variables described about PU, was 19.10%.
      CONCLUSIONS: The incidence of pressure ulcers was lower than in the current
      literature. The most frequent category, location and clinical characteristics are
      comparable to previous studies. There is a high rate of failing to record the
      characteristics of the PU declared. Good PU prevention measures and recording
      were carried out.

PMID- 30190249
TI  - Nurse methodology applied to clinical practice: Reality or fiction?

PMID- 30190250
TI  - Complications related to the insertion and maintenance of peripheral venous
      access central venous catheter.
AB  - OBJECTIVE: To evaluate the rates and nature of the complications related to the
      Central Peripheral Access Catheter (CVCAP or PICC) from its insertion to its
      withdrawal. METHODS: Prospective observational study. All patients older than 14
      years of age with a PICC inserted in the polyvalent intensive care unit (ICU)
      during the period between May 1, 2015 and April 30, 2016 were included. Data
      collected included: demographic data, insertion details, reason for insertion and
      removal, maintenance unit, total dwell time, incidence of complications and
      related factors and infection rate. RESULTS: 144 PICCs were inserted, of which 94
      corresponded to the ICU group (65.28%) and 50 (34.72%) to the non-ICU group. The
      most important complication was the suspicion of infection: 17.36% (rate of 15.2
      per 1000 days of PICC). The total number of confirmed infections was 6.25% (5.5
      per 1000 days of PICC), 1.39% (1.2 per 1000 days) being in the ICU group and
      4.86% (4.2 per 1000 days) in the non-ICU group. There were 5 bacteraemias, all in
      the non-ICU group (3 per 1000 days). The most frequent germ was Staphylococcus
      epidermidis (6 cases). Phlebitis had an incidence of 9.03% (7.9 per 1000 days of
      PICC). CONCLUSIONS: PICC, effective device for central venous access due to the
      minimal incidence of risks in implantation and to its advantages with regard to
      the classic central venous catheters, is a further nursing technique.

PMID- 30190251
TI  - Construction of an attenuated Tian Tan vaccinia virus strain by deletion of TA35R
      and TJ2R genes.
AB  - rVTT-TA35-TJ, an attenuated vaccinia virus Tian Tan strain (VTT), was constructed
      by knocking out two non-essential gene fragments (TA35R and TJ2R) related to
      virulence, immunomodulation, and host range; and by combining double marker
      screening with exogenous and endogenous selectable marker knock-out techniques.
      Here, the shuttle plasmids pSK-TA35 and pSK-TJ were constructed, containing two
      pairs of recombinant arms: early and late strong promoter pE/L and EGFP as an
      exogenous selectable marker. The recombinant vaccinia virus rVTT-TA35-TJ without
      exogenous selection markers was then obtained through homologous recombination
      technology and the Cre/loxP system. Knocking out the two gene fragments does not
      affect the replication ability of the virus and displays a good genetic
      stability. Furthermore, a series of in vivo and in vitro experiments demonstrate
      that although virulence of rVTT-TA35-TJ is attenuated significantly, high
      immunogenicity was maintained. These results support the potential development of
      rVTT-TA35-TJ as a safe viral vector or vaccine.

PMID- 30190254
TI  - Use of Electronic Entertainment and Communication Devices Among a Saudi Pediatric
      Population: Cross-Sectional Study.
AB  - BACKGROUND: Excessive use of various electronic entertainment and communication
      devices, particularly among children, has been associated with increased
      behavioral problems. Despite children's escalating use of these devices, parents'
      awareness about the impact thereof is still lacking. OBJECTIVE: The objective of
      this study was to assess the use of electronic entertainment and communication
      devices among children attending a health care facility in Jeddah, Saudi Arabia,
      as well as the parental impression regarding the impact of electronic devices use
      on the behavior of their child. METHODS: A focused 15-item questionnaire was
      designed for this cross-sectional study involving mothers of children attending
      the Well Baby Clinic of King Abdulaziz University Hospital, Jeddah, Saudi Arabia
      from July 1, 2016 to November 30, 2016. RESULTS: This study included 190 mothers.
      The mean ages of the children, mothers, and fathers were 7.3 (SD 3.5), 35 (SD
      6.5), and 43 (SD 8.3) years, respectively. Most children were of Saudi Arabian
      nationality (106/190, 55.8%). The most used device in this study was television
      (154/190, 81.0%), followed by mobile phones (134/190, 70.5%), and tablets
      (116/190, 61.0%). Computers were the least used device in this study (59/190,
      31.0%). In total, 24.7% (47/190) of children in this study used electronic
      entertainment and communication devices for more than 4 hours per day. Most
      mothers (129/190, 67.9%) felt that their child spends too much time on electronic
      devices. Hyperactivity or behavioral problems were reported by 20.0% (38/190) of
      mothers in this study. Children spending longer hours on electronic devices were
      much more likely to be perceived to suffer from hyperactivity or behavioral
      problems (P=.01). CONCLUSIONS: Parental awareness is necessary to counteract the
      harmful effects of using electronic devices for a prolonged period. Parents
      require help to cope with this problem effectively.

PMID- 30190255
TI  - Comment on "Blood Flow Mimicking Aneurysmal Wall Enhancement: A Diagnostic
      Pitfall of Vessel Wall MRI Using the Postcontrast 3D Turbo Spin-Echo MR Imaging
      Sequence".

PMID- 30190252
TI  - Individualized Clinical Practice Guidelines for Pressure Injury Management:
      Development of an Integrated Multi-Modal Biomedical Information Resource.
AB  - BACKGROUND: Pressure ulcers (PU) and deep tissue injuries (DTI), collectively
      known as pressure injuries are serious complications causing staggering costs and
      human suffering with over 200 reported risk factors from many domains. Primary
      pressure injury prevention seeks to prevent the first incidence, while secondary
      PU/DTI prevention aims to decrease chronic recurrence. Clinical practice
      guidelines (CPG) combine evidence-based practice and expert opinion to aid
      clinicians in the goal of achieving best practices for primary and secondary
      prevention. The correction of all risk factors can be both overwhelming and
      impractical to implement in clinical practice. There is a need to develop
      practical clinical tools to prioritize the multiple recommendations of CPG, but
      there is limited guidance on how to prioritize based on individual cases.
      Bioinformatics platforms enable data management to support clinical decision
      support and user-interface development for complex clinical challenges such as
      pressure injury prevention care planning. OBJECTIVE: The central hypothesis of
      the study is that the individual's risk factor profile can provide the basis for
      adaptive, personalized care planning for PU prevention based on CPG
      prioritization. The study objective is to develop the Spinal Cord Injury Pressure
      Ulcer and Deep Tissue Injury (SCIPUD+) Resource to support personalized care
      planning for primary and secondary PU/DTI prevention. METHODS: The study is
      employing a retrospective electronic health record (EHR) chart review of over 75
      factors known to be relevant for pressure injury risk in individuals with a
      spinal cord injury (SCI) and routinely recorded in the EHR. We also perform
      tissue health assessments of a selected sub-group. A systems approach is being
      used to develop and validate the SCIPUD+ Resource incorporating the many risk
      factor domains associated with PU/DTI primary and secondary prevention, ranging
      from the individual's environment to local tissue health. Our multiscale approach
      will leverage the strength of bioinformatics applied to an established national
      EHR system. A comprehensive model is being used to relate the primary outcome of
      interest (PU/DTI development) with over 75 PU/DTI risk factors using a
      retrospective chart review of 5000 individuals selected from the study cohort of
      more than 36,000 persons with SCI. A Spinal Cord Injury Pressure Ulcer and Deep
      Tissue Injury Ontology (SCIPUDO) is being developed to enable robust text-mining
      for data extraction from free-form notes. RESULTS: The results from this study
      are pending. CONCLUSIONS: PU/DTI remains a highly significant source of morbidity
      for individuals with SCI. Personalized interactive care plans may decrease both
      initial PU formation and readmission rates for high-risk individuals. The project
      is using established EHR data to build a comprehensive, structured model of
      environmental, social and clinical pressure injury risk factors. The
      comprehensive SCIPUD+ health care tool will be used to relate the primary outcome
      of interest (pressure injury development) with covariates including
      environmental, social, clinical, personal and tissue health profiles as well as
      possible interactions among some of these covariates. The study will result in a
      validated tool for personalized implementation of CPG recommendations and has
      great potential to change the standard of care for PrI clinical practice by
      enabling clinicians to provide personalized application of CPG priorities
      tailored to the needs of each at-risk individual with SCI. REGISTERED REPORT
      IDENTIFIER: RR1-10.2196/10871.

PMID- 30190253
TI  - Proposing an Ecosystem of Digital Health Solutions for Teens With Chronic
      Conditions Transitioning to Self-Management and Independence: Exploratory
      Qualitative Study.
AB  - BACKGROUND: Chronic disease management is critical to quality of life for both
      teen patients with chronic conditions and their caregivers. However, current
      literature is largely limited to a specific digital health tool, method, or
      approach to manage a specific disease. Guiding principles on how to use digital
      tools to support the transition to independence are rare. Considering the
      physiological, psychological, and environmental changes that teens experience,
      the issues surrounding the transition to independence are worth investigating to
      develop a deeper understanding to inform future strategies for digital
      interventions. OBJECTIVE: The purpose of this study was to inform the design of
      digital health solutions by systematically identifying common challenges among
      teens and caregivers living with chronic diseases. METHODS: Chronically ill teens
      (n=13) and their caregivers (n=13) were interviewed individually and together as
      a team. Verbal and projective techniques were used to examine teens' and
      caregivers' concerns in-depth. The recorded and transcribed responses were
      thematically analyzed to identify and organize the identified patterns. RESULTS:
      Teens and their caregivers identified 10 challenges and suggested technological
      solutions. Recognized needs for social support, access to medical education,
      symptom monitoring, access to health care providers, and medical supply
      management were the predominant issues. The envisioned ideal transition included
      a 5-component solution ecosystem in the transition to independence for teens.
      CONCLUSIONS: This novel study systematically summarizes the challenges, barriers,
      and technological solutions for teens with chronic conditions and their
      caregivers as teens transition to independence. A new solution ecosystem based on
      the 10 identified challenges would guide the design of future implementations to
      test and validate the effectiveness of the proposed 5-component ecosystem.

PMID- 30190256
TI  - Reply.

PMID- 30190257
TI  - Apparent Diffusion Coefficient Levels and Neurodevelopmental Outcome in Fetuses
      with Brain MR Imaging White Matter Hyperintense Signal.
AB  - BACKGROUND AND PURPOSE: One of the perplexing findings of fetal brain MR imaging
      is white matter T2 hyperintense signal. The aims of our study were initially to
      determine the main etiologies associated with white matter T2 hyperintense
      signal, then to examine whether the different etiologies have different ADC
      values, and, last, to assess the association of white matter T2 hyperintense
      signal with developmental outcome. MATERIALS AND METHODS: This was a prospective
      cohort study of 44 MR imaging scans of fetal brains obtained for suspected brain
      pathologies at a tertiary medical center during 2011-2015. Clinical data were
      collected from electronic medical charts. ADC values were measured and averaged
      in the frontal, parietal, occipital, and temporal lobes. Neurodevelopmental
      assessments were performed with the Vineland Adaptive Behavior Scales II.
      RESULTS: Half of the cases of MRI hyperintense T2 signal of the fetal brain were
      associated with congenital cytomegalovirus infection. The other half were mainly
      idiopathic. Thus, the study group was divided to subgroups positive and negative
      for cytomegalovirus. Both groups had hyperintense signal in the temporal lobe.
      The group positive for cytomegalovirus had involvement of the parietal lobe. Only
      this group had increased ADC values in the temporal and parietal lobes. There was
      no association between the neurodevelopment outcome and the etiologies or ADC
      values. CONCLUSIONS: T2 hyperintense signal in fetal brain MRI associated with
      positive cytomegalovirus infection has increased ADC values in the temporal and
      parietal lobes, suggestive of brain edema in these areas. However, the
      association between this finding and neurodevelopment outcome requires further
      evaluation.

PMID- 30190258
TI  - Near-Term Decrease in Brain Volume following Mild Traumatic Injury Is Detectible
      in the Context of Preinjury Volumetric Stability: Neurobiologic Insights from
      Analysis of Historical Imaging Examinations.
AB  - BACKGROUND AND PURPOSE: Neurodegeneration after mild traumatic brain injury may
      manifest as decreasing regional brain volume that evolves from months to years
      following mild traumatic brain injury and is associated with worse clinical
      outcomes. We hypothesized that quantitative brain volume derived from CT of the
      head, performed for clinical indications during routine care, would change with
      time and provide insights into the putative neuroinflammatory response to mild
      traumatic brain injury. MATERIALS AND METHODS: We searched the electronic medical
      record of our institution for NCCTs of the head performed in patients with mild
      traumatic brain injury and included those who also underwent NCCTs of the head 1
      month to 1 year before and after mild traumatic brain injury for an indication
      unrelated to trauma. Controls underwent 3 sequential NCCTs of the head with
      indications unrelated to trauma. The whole-brain and intracranial volume groups
      were computed using ITK-SNAP. Brain volumes normalized to intracranial volumes
      were compared across time points using the Wilcoxon signed-rank test. RESULTS: We
      identified 48 patients from 2005 to 2015 who underwent NCCTs of the head in the
      emergency department for mild traumatic brain injury and had NCCTs of the head
      performed both before and after mild traumatic brain injury. Median normalized
      brain volumes significantly decreased on the follow-up study post-mild traumatic
      brain injury (0.86 versus 0.84, P < .001) and were similar compared with pre-mild
      traumatic brain injury studies (0.87 versus 0.86, P = .927). There was no
      significant difference between normalized brain volumes in the 48 controls.
      CONCLUSIONS: A decrease in brain volume following mild traumatic brain injury is
      detectable on CT and is not seen in similar patients with non-mild traumatic
      brain injury during a similar timeframe. Given the stability of brain volume
      before mild traumatic brain injury, CT volume loss may represent the subtle
      effects of neurodegeneration.

PMID- 30190259
TI  - Predicting Genotype and Survival in Glioma Using Standard Clinical MR Imaging
      Apparent Diffusion Coefficient Images: A Pilot Study from The Cancer Genome
      Atlas.
AB  - BACKGROUND AND PURPOSE: Few studies have shown MR imaging features and ADC
      correlating with molecular markers and survival in patients with glioma. Our
      purpose was to correlate MR imaging features and ADC with molecular subtyping and
      survival in adult diffuse gliomas. MATERIALS AND METHODS: Presurgical MRIs and
      ADC maps of 131 patients with diffuse gliomas and available molecular and
      survival data from The Cancer Genome Atlas were reviewed. MR imaging features,
      ADC (obtained by ROIs within the lowest ADC area), and mean relative ADC values
      were evaluated to predict isocitrate dehydrogenase (IDH) mutation, 1p/19q
      codeletion status, MGMT promoter methylation, and overall survival. RESULTS: IDH
      wild-type gliomas tended to exhibit enhancement, necrosis, and edema; >50%
      enhancing area (P < .001); absence of a cystic area (P = .013); and lower mean
      relative ADC (median, 1.1 versus 1.6; P < .001) than IDH-mutant gliomas. By means
      of a cutoff value of 1.08 for mean relative ADC, IDH-mutant and IDH wild-type
      gliomas with lower mean relative ADC (<1.08) had poorer survival than those with
      higher mean relative ADC (median survival time, 24.2 months; 95% CI, 0.0-54.9
      months versus 62.0 months; P = .003; and median survival time, 10.4 months; 95%
      CI, 4.4-16.4 months versus 17.7 months; 95% CI, 11.6-23.7 months; P = .041,
      respectively), regardless of World Health Organization grade. Median survival of
      those with IDH-mutant glioma with low mean relative ADC was not significantly
      different from that in those with IDH wild-type glioma. Other MR imaging features
      were not statistically significant predictors of survival. CONCLUSIONS: IDH wild
      type glioma showed lower ADC values, which also correlated with poor survival in
      both IDH-mutant and IDH wild-type gliomas, irrespective of histologic grade. A
      subgroup with IDH-mutant gliomas with lower ADC had dismal survival similar to
      that of those with IDH wild-type gliomas.

PMID- 30190260
TI  - Electronic cigarette vapour enhances pneumococcal adherence to airway epithelial
      cells under abnormal conditions of exposure.

PMID- 30190261
TI  - The limitations of cross-sectional data: perinatal risk factors for asthma.

PMID- 30190262
TI  - Response to: Electronic cigarette vapour enhances pneumococcal adherence to
      airway epithelial cells under abnormal conditions of exposure.

PMID- 30190263
TI  - Treatable traits in bronchiectasis.

PMID- 30190264
TI  - Phenotyping primary spontaneous pneumothorax.

PMID- 30190265
TI  - Diagnosing idiopathic pulmonary fibrosis in 2018: bridging recommendations made
      by experts serving different societies.

PMID- 30190266
TI  - A Pragmatic Method for Identification of Long-Stay Patients in the PICU.
AB  - OBJECTIVES: To develop a pragmatic method of identifying long-stay patients
      (LSPs) in the PICU. METHODS: We surveyed 40 expert stakeholders in 14 Canadian
      PICUs between February 2015 and March 2015 to identify key factors to use for
      defining LSPs in the PICU. We then describe a pragmatic method using these
      factors to analyze 523 admissions to an academic, tertiary-care PICU from
      February 1, 2015, to January 31, 2016. RESULTS: The overall response rate was 70%
      (28 of 40). Of respondents, 75% (21of 28) stated that it was important to define
      LSPs and identified present and future resource consumption (18 of 21 [86%] and
      16 of 21 [76%], respectively) as the key reasons for defining LSPs. Respondents
      valued a definition that was consistent and ranked a percentile cutoff as the
      preferred analytic method for defining LSPs. Of respondents, 86% (24 of 28)
      though the LSP definition should include factors other than length of stay. We
      developed a surrogate marker for LSPs using mechanical ventilation and presence
      of a central venous catheter in our sample population to compare to varying
      percentile cutoffs. We identified 108 patients at the 80th percentile as LSPs who
      used 67% of total bed days and had a median length of stay of 11.3 days.
      CONCLUSIONS: We present a pragmatic method for the retrospective identification
      of LSPs in the PICU that incorporates unit- and/or patient-specific
      characteristics. The next steps would be to validate this method using other
      patient and/or unit characteristics in different PICUs and over time.

PMID- 30190268
TI  - SPLUNC1 degradation by the cystic fibrosis mucosal environment drives airway
      surface liquid dehydration.
AB  - The multi-organ disease cystic fibrosis (CF) is caused by mutations in the cystic
      fibrosis transmembrane regulator gene (CFTR) that lead to diminished
      transepithelial anion transport. CF lungs are characterised by airway surface
      liquid (ASL) dehydration, chronic infection/inflammation and neutrophilia.
      Dysfunctional CFTR may upregulate the epithelial Na+ channel (ENaC), further
      exacerbating dehydration. We previously demonstrated that short palate lung and
      nasal epithelial clone 1 (SPLUNC1) negatively regulates ENaC in normal airway
      epithelia.Here, we used pulmonary tissue samples, sputum and human bronchial
      epithelial cells (HBECs) to determine whether SPLUNC1 could regulate ENaC in a CF
      like environment.We found reduced endogenous SPLUNC1 in CF secretions, and rapid
      degradation of recombinant SPLUNC1 (rSPLUNC1) by CF secretions. Normal sputum,
      containing SPLUNC1 and SPLUNC1-derived peptides, inhibited ENaC in both normal
      and CF HBECs. Conversely, CF sputum activated ENaC, and rSPLUNC1 could not
      reverse this phenomenon. Additionally, we observed upregulation of ENaC protein
      levels in human CF bronchi. Unlike SPLUNC1, the novel SPLUNC1-derived peptide SPX
      101 resisted protease degradation, bound apically to HBECs, inhibited ENaC and
      prevented ASL dehydration following extended pre-incubation with CF sputum.Our
      data indicate that CF mucosal secretions drive ASL hyperabsorption and that
      protease-resistant peptides, e.g. SPX-101, can reverse this effect to rehydrate
      CF ASL.

PMID- 30190269
TI  - Inhaled corticosteroids in COPD: Friend or foe?
AB  - The efficacy, safety and positioning of inhaled corticosteroids (ICS) in the
      treatment of patients with chronic obstructive pulmonary disease (COPD) is much
      debated, since it can result in clear clinical benefits in some patients
      ("friend") but can be ineffective or even associated with undesired side effects,
      e.g. pneumonia, in others ("foe"). After critically reviewing the evidence for
      and against ICS treatment in patients with COPD, we propose that: 1) ICS should
      not be used as a single, stand-alone therapy in COPD; 2) patients most likely to
      benefit from the addition of ICS to long-acting bronchodilators include those
      with history of multiple or severe exacerbations despite appropriate maintenance
      bronchodilator use, particularly if blood eosinophils are >300 cells.uL-1, and
      those with a history of and/or concomitant asthma; and 3) the risk of pneumonia
      in COPD patients using ICS is higher in those with older age, lower body mass
      index, greater overall fragility, receiving higher ICS doses and those with blood
      eosinophils <100 cells.uL-1 All these factors must be carefully considered and
      balanced in any individual COPD patient before adding ICS to her/his maintenance
      bronchodilator treatment. Further research is needed to clarify some of these
      issues and firmly establish these recommendations.

PMID- 30190267
TI  - Neuronal cell culture from transgenic zebrafish models of neurodegenerative
      disease.
AB  - We describe a protocol for culturing neurons from transgenic zebrafish embryos to
      investigate the subcellular distribution and protein aggregation status of
      neurodegenerative disease-causing proteins. The utility of the protocol was
      demonstrated on cell cultures from zebrafish that transgenically express disease
      causing variants of human fused in sarcoma (FUS) and ataxin-3 proteins, in order
      to study amyotrophic lateral sclerosis (ALS) and spinocerebellar ataxia type-3
      (SCA3), respectively. A mixture of neuronal subtypes, including motor neurons,
      exhibited differentiation and neurite outgrowth in the cultures. As reported
      previously, mutant human FUS was found to be mislocalized from nuclei to the
      cytosol, mimicking the pathology seen in human ALS and the zebrafish FUS model.
      In contrast, neurons cultured from zebrafish expressing human ataxin-3 with
      disease-associated expanded polyQ repeats did not accumulate within nuclei in a
      manner often reported to occur in SCA3. Despite this, the subcellular
      localization of the human ataxin-3 protein seen in cell cultures was similar to
      that found in the SCA3 zebrafish themselves. The finding of similar protein
      localization and aggregation status in the neuronal cultures and corresponding
      transgenic zebrafish models confirms that this cell culture model is a useful
      tool for investigating the cell biology and proteinopathy signatures of mutant
      proteins for the study of neurodegenerative disease.

PMID- 30190270
TI  - Detection of mild cognitive impairment in middle-aged and older adults with
      obstructive sleep apnoea.
AB  - Obstructive sleep apnoea increases the risk for mild cognitive impairment and
      dementia. The present study aimed to characterise the ability of two cognitive
      screening tests, the Mini-Mental State Examination and the Montreal Cognitive
      Assessment, to detect mild cognitive impairment in adults aged 55-85 years with
      and without obstructive sleep apnoea.We included 42 subjects with mild and 67
      subjects with moderate-to-severe obstructive sleep apnoea. We compared them to 22
      control subjects. Mild cognitive impairment was diagnosed by a comprehensive
      neuropsychological assessment. We used receiver operating characteristic curves
      to assess the ability of the two screening tests to detect mild cognitive
      impairment.The two screening tests showed similar discriminative ability in
      control subjects. However, among the mild and the moderate-to-severe obstructive
      sleep apnoea groups, the Mini-Mental State Examination was not able to correctly
      identify subjects with mild cognitive impairment. The Montreal Cognitive
      Assessment's discriminant ability was acceptable in both sleep apnoea groups and
      was comparable to what was observed in controls.The Mini-Mental State Examination
      should not be used to screen for cognitive impairment in patients with
      obstructive sleep apnoea. The Montreal Cognitive Assessment could be used in
      clinical settings. However, clinicians should refer patients for
      neuropsychological assessment when neurodegenerative processes are suspected.

PMID- 30190271
TI  - The "one airway, one disease" concept in light of Th2 inflammation.
AB  - In line with the pathophysiological continuum described between nose and bronchus
      in allergic respiratory diseases, we assessed whether nasal epithelium could
      mirror the Type 2 T-helper cell (Th2) status of bronchial epithelium.Nasal and
      bronchial cells were collected by brushing from healthy controls (C, n=13),
      patients with allergic rhinitis and asthma (AR, n=12), and patients with isolated
      allergic rhinitis (R, n=14). Cellular composition was assessed by flow cytometry,
      gene expression was analysed by RNA sequencing and Th2, Type 17 T-helper cell
      (Th17) and interferon (IFN) signatures were derived from the
      literature.Infiltration by polymorphonuclear neutrophils (PMN) in the nose
      excluded 30% of the initial cohort. All bronchial samples from the AR group were
      Th2-high. The gene expression profile of nasal samples from the AR group
      correctly predicted the paired bronchial sample Th2 status in 71% of cases.
      Nevertheless, nasal cells did not appear to be a reliable surrogate for the Th2
      response, in particular due to a more robust influence of the IFN response in 14
      out of 26 nasal samples. The Th2 scores in the nose and bronchi correlated with
      mast cell count (both p<0.001) and number of sensitisations (p=0.006 and 0.002),
      while the Th17 scores correlated with PMN count (p=0.006 and 0.003).The large
      variability in nasal cell composition and type of inflammation restricts its use
      as a surrogate for assessing bronchial Th2 inflammation in AR patients.

PMID- 30190272
TI  - The DNA repair transcriptome in severe COPD.
AB  - Inadequate DNA repair is implicated in the pathogenesis of chronic obstructive
      pulmonary disease (COPD). However, the mechanisms that underlie inadequate DNA
      repair in COPD are poorly understood. We applied an integrative genomic approach
      to identify DNA repair genes and pathways associated with COPD severity.We
      measured the transcriptomic changes of 419 genes involved in DNA repair and DNA
      damage tolerance that occur with severe COPD in three independent cohorts
      (n=1129). Differentially expressed genes were confirmed with RNA sequencing and
      used for patient clustering. Clinical and genome-wide transcriptomic differences
      were assessed following cluster identification. We complemented this analysis by
      performing gene set enrichment analysis, Z-score and weighted gene correlation
      network analysis to identify transcriptomic patterns of DNA repair pathways
      associated with clinical measurements of COPD severity.We found 15 genes involved
      in DNA repair and DNA damage tolerance to be differentially expressed in severe
      COPD. K-means clustering of COPD cases based on this 15-gene signature identified
      three patient clusters with significant differences in clinical characteristics
      and global transcriptomic profiles. Increasing COPD severity was associated with
      downregulation of the nucleotide excision repair pathway.Systematic analysis of
      the lung tissue transcriptome of individuals with severe COPD identified DNA
      repair responses associated with disease severity that may underlie COPD
      pathogenesis.

PMID- 30190273
TI  - Myeloperoxidase oxidation of methionine associates with early cystic fibrosis
      lung disease.
AB  - Cystic fibrosis (CF) lung disease progressively worsens from infancy to
      adulthood. Disease-driven changes in early CF airway fluid metabolites may
      identify therapeutic targets to curb progression.CF patients aged 12-38 months
      (n=24; three out of 24 later denoted as CF screen positive, inconclusive
      diagnosis) received chest computed tomography scans, scored by the Perth
      Rotterdam Annotated Grid Morphometric Analysis for CF (PRAGMA-CF) method to
      quantify total lung disease (PRAGMA-%Dis) and components such as bronchiectasis
      (PRAGMA-%Bx). Small molecules in bronchoalveolar lavage fluid (BALF) were
      measured with high-resolution accurate-mass metabolomics. Myeloperoxidase (MPO)
      was quantified by ELISA and activity assays.Increased PRAGMA-%Dis was driven by
      bronchiectasis and correlated with airway neutrophils. PRAGMA-%Dis correlated
      with 104 metabolomic features (p<0.05, q<0.25). The most significant annotated
      feature was methionine sulfoxide (MetO), a product of methionine oxidation by MPO
      derived oxidants. We confirmed the identity of MetO in BALF and used reference
      calibration to confirm correlation with PRAGMA-%Dis (Spearman's rho=0.582,
      p=0.0029), extending to bronchiectasis (PRAGMA-%Bx; rho=0.698, p=1.5*10-4),
      airway neutrophils (rho=0.569, p=0.0046) and BALF MPO (rho=0.803, p=3.9*10
      6).BALF MetO associates with structural lung damage, airway neutrophils and MPO
      in early CF. Further studies are needed to establish whether methionine oxidation
      directly contributes to early CF lung disease and explore potential therapeutic
      targets indicated by these findings.

PMID- 30190274
TI  - Consequences of long-term oral corticosteroid therapy and its side-effects in
      severe asthma in adults: a focused review of the impact data in the literature.
AB  - This review provides an overview of the role of long-term treatment of severe
      asthma with oral corticosteroids (OCS) and its associated side-effects in adults.
      It is based on a systematic literature search conducted in MEDLINE, Embase and
      the Cochrane Library to identify relevant studies. After a short overview of
      severe asthma and its treatment we present studies showing a dose-response
      relationship in asthmatic patients treated with OCS and then consider by organ
      systems the undesired effects demonstrated in clinical and epidemiological
      studies in patients with OCS-dependent asthma. It was found that the risk of
      developing various OCS-related complications, including infections, diabetes and
      osteoporosis as well as psychiatric disorders, was higher for patients with long
      term exposure to OCS compared with control groups. In addition, studies showed a
      significant increase in healthcare resource utilisation due to OCS treatment.
      Therefore, it is incumbent on every clinician to carefully weigh the potential
      benefit of preventing loss of asthma control against this risk before opting to
      prescribe long-term OCS therapy. Effective corticosteroid-sparing strategies must
      be used and should aim at short-term use with the lowest effective dose and start
      tapering as soon as possible until OCS therapy is terminated.

PMID- 30190275
TI  - Pulmonary function testing is safe in patients with thoracic aortic aneurysms.

PMID- 30190276
TI  - Benefits, Harms, and Cost-Effectiveness of Potential Age Extensions to the
      National Bowel Cancer Screening Program in Australia.
AB  - BACKGROUND: The Australian National Bowel Cancer Screening Program (NBCSP) is
      rolling out 2-yearly immunochemical fecal occult blood test screening in people
      aged 50 to 74 years. This study aimed to evaluate the benefits, harms, and cost
      effectiveness of extending the NBCSP to younger and/or older ages. METHODS: A
      comprehensive validated microsimulation model, Policy1-Bowel, was used to
      simulate the fully rolled-out NBCSP and alternative strategies assuming screening
      starts at 40 or 45 years and/or ceases at 79 or 84 years given three scenarios:
      (i) perfect adherence (100%), (ii) high adherence (60%), and (ii) low adherence
      (40%, as currently achieved). RESULTS: The current NBCSP will reduce colorectal
      cancer incidence (mortality) by 23% to 51% (36% to 74%) compared with no
      screening (range reflects participation); extending screening to younger or older
      ages would result in additional reductions of 2 to 6 (2 to 9) or 1 to 3 (3 to 7)
      percentage points, respectively. With an indicative willingness-to-pay threshold
      of A$50,000/life-year saved (LYS), only screening from 50 to 74 years
      [incremental cost-effective ratio (ICER): A$2,984-5,981/LYS) or from 45 to 74
      years (ICER: A$17,053-29,512/LYS) remained cost-effective in all participation
      scenarios. The number-needed-to-colonoscope to prevent a death over the lifetime
      of a cohort in the current NBCSP is 35 to 49. Starting screening at 45 years
      would increase colonoscopy demand for program-related colonoscopies by 3% to 14%
      and be associated with 55 to 170 additional colonoscopies per additional death
      prevented. CONCLUSIONS: Starting screening at 45 years could be cost-effective,
      but it would increase colonoscopy demand and would be associated with a less
      favorable incremental benefits-to-harms trade-off than screening from 50 to 74
      years. IMPACT: The study underpins recently updated Australian colorectal cancer
      management guidelines that recommend that the NBCSP continues to offer bowel
      screening from 50 to 74 years.

PMID- 30190278
TI  - Variant PRC1 competes with retinoic acid-related signals to repress Meis2 in the
      mouse distal forelimb bud.
AB  - Suppression of Meis genes in the distal limb bud is required for proximal-distal
      (PD) specification of the forelimb. Polycomb group (PcG) factors play a role in
      downregulation of retinoic acid (RA)-related signals in the distal forelimb bud,
      causing Meis repression. It is, however, not known whether downregulation of RA
      related signals and PcG-mediated proximal gene repression are functionally
      linked. Here, we reveal that PcG factors and RA-related signals antagonize each
      other to polarize Meis2 expression along the PD axis in mouse. Supported by
      mathematical modeling and simulation, we propose that PcG factors are required to
      adjust the threshold for RA-related signaling to regulate Meis2 expression.
      Finally, we show that a variant Polycomb repressive complex 1 (PRC1),
      incorporating PCGF3 and PCGF5, represses Meis2 expression in the distal limb bud.
      Taken together, we reveal a previously unknown link between PcG proteins and
      downregulation of RA-related signals to mediate the phase transition of Meis2
      transcriptional status during forelimb patterning.

PMID- 30190280
TI  - Cell wall integrity modulates Arabidopsis thaliana cell cycle gene expression in
      a cytokinin- and nitrate reductase-dependent manner.
AB  - During plant growth and defense, cell cycle activity needs to be coordinated with
      cell wall integrity. Little is known about how this coordination is achieved.
      Here, we investigated coordination in Arabidopsis thaliana seedlings by studying
      the impact of cell wall damage (CWD, caused by cellulose biosynthesis inhibition)
      on cytokinin homeostasis, cell cycle gene expression and cell shape in root tips.
      CWD inhibited cell cycle gene expression and increased transition zone cell width
      in an osmosensitive manner. These results were correlated with CWD-induced,
      osmosensitive changes in cytokinin homeostasis. Expression of CYTOKININ
      OXIDASE/DEHYDROGENASE 2 and 3 (CKX2, CKX3), which encode cytokinin-degrading
      enzymes, was induced by CWD and reduced by osmoticum treatment. In nitrate
      reductase1 nitrate reductase2 (nia1 nia2) seedlings, CKX2 and CKX3 transcript
      levels were not increased and cell cycle gene expression was not repressed by
      CWD. Moreover, established CWD-induced responses, such as jasmonic acid,
      salicylic acid and lignin production, were also absent, implying a central role
      of NIA1/2-mediated processes in regulation of CWD responses. These results
      suggest that CWD enhances cytokinin degradation rates through a NIA1/2-mediated
      process, leading to attenuation of cell cycle gene expression.

PMID- 30190277
TI  - FGF controls epithelial-mesenchymal transitions during gastrulation by regulating
      cell division and apicobasal polarity.
AB  - To support tissue and organ development, cells transition between epithelial and
      mesenchymal states. Here, we have investigated how mesoderm cells change state in
      Drosophila embryos and whether fibroblast growth factor (FGF) signaling plays a
      role. During gastrulation, presumptive mesoderm cells invaginate, undergo an
      epithelial-to-mesenchymal state transition (EMT) and migrate upon the ectoderm.
      Our data show that EMT is a prolonged process in which adherens junctions
      progressively decrease in number throughout the migration of mesoderm cells. FGF
      influences adherens junction number and promotes mesoderm cell division, which we
      propose decreases cell-cell attachments to support slow EMT while retaining
      collective cell movement. We also found that, at the completion of migration,
      cells form a monolayer and undergo a reverse mesenchymal-to-epithelial transition
      (MET). FGF activity leads to accumulation of beta-integrin Myospheroid basally
      and cell polarity factor Bazooka apically within mesoderm cells, thereby
      reestablishing apicobasal cell polarity in an epithelialized state in which cells
      express both E-Cadherin and N-Cadherin. In summary, FGF plays a dynamic role in
      supporting mesoderm cell development to ensure collective mesoderm cell
      movements, as well as proper differentiation of mesoderm cell types.

PMID- 30190279
TI  - Multiscale analysis of architecture, cell size and the cell cortex reveals
      cortical F-actin density and composition are major contributors to mechanical
      properties during convergent extension.
AB  - The large-scale movements that construct complex three-dimensional tissues during
      development are governed by universal physical principles. Fine-grained control
      of both mechanical properties and force production is crucial to the successful
      placement of tissues and shaping of organs. Embryos of the frog Xenopus laevis
      provide a dramatic example of these physical processes, as dorsal tissues
      increase in Young's modulus by six-fold to 80 Pascal over 8 h as germ layers and
      the central nervous system are formed. These physical changes coincide with
      emergence of complex anatomical structures, rounds of cell division, and
      cytoskeletal remodeling. To understand the contribution of these diverse
      structures, we adopt the cellular solids model to relate bulk stiffness of a
      solid foam to the unit size of individual cells, their microstructural
      organization, and their material properties. Our results indicate that large
      scale tissue architecture and cell size are not likely to influence the bulk
      mechanical properties of early embryonic or progenitor tissues but that F-actin
      cortical density and composition of the F-actin cortex play major roles in
      regulating the physical mechanics of embryonic multicellular tissues.

PMID- 30190282
TI  - Immune checkpoint inhibitors as a bridge to allogeneic transplantation with
      posttransplant cyclophosphamide.
AB  - Published reports suggest that immune checkpoint inhibitors (ICIs) before
      allogeneic blood or marrow transplantation (alloBMT) may increase the incidence
      of graft-versus-host disease (GvHD), immune-related adverse events, and
      nonrelapse mortality (NRM); this led to the US Food and Drug Administration
      issuing a "Warning and Precaution" regarding the potential for life-threatening
      immune-mediated complications associated with alloBMT after nivolumab and
      pembrolizumab. We retrospectively reviewed the outcomes of 14 consecutive
      patients who received ICIs as their final salvage therapy before T-cell-replete
      alloBMT using reduced-intensity conditioning. All patients received
      posttransplant cyclophosphamide (PTCy), which significantly limits severe GvHD,
      even in the mismatched-donor setting. There was no grade 3-4 acute GvHD (aGvHD),
      and all 6 cases of grade 2 aGvHD readily resolved with immunosuppression. No
      patient experienced veno-occlusive disease of the liver, other immune-related
      adverse events, chronic GvHD, or NRM. There have been 2 relapses (15-month median
      follow-up), with 12 of 14 patients remaining alive, well, and progression-free.
      The only death was a result of disease relapse. Although more experience is
      needed, our data suggest that concerns over immunologic complications associated
      with ICIs should not preclude allogeneic bone marrow transplantation with PTCy as
      GvHD prophylaxis.

PMID- 30190283
TI  - Milk, mucus and myths.

PMID- 30190281
TI  - Cobalt hematoporphyrin inhibits CLEC-2-podoplanin interaction, tumor metastasis,
      and arterial/venous thrombosis in mice.
AB  - The platelet activation receptor C-type lectin-like receptor 2 (CLEC-2) interacts
      with podoplanin on the surface of certain types of tumor cells, and this
      interaction facilitates tumor metastasis. CLEC-2 is also involved in thrombus
      formation and its stabilization. Because CLEC-2-depleted mice are protected from
      experimental lung metastasis and thrombus formation and do not show increased
      bleeding time, CLEC-2 may serve as a good target for antimetastatic or
      antithrombotic drugs. We screened 6770 compounds for their capability to inhibit
      CLEC-2-podoplanin binding using an enzyme-linked immunosorbent assay. In the
      first screening round, 63 compounds were identified and further evaluated by flow
      cytometry using CLEC-2-expressing cells. We identified protoporphyrin IX (H2-PP)
      as the most potent inhibitor and modified its hematoporphyrin moiety to be
      complexed with cobalt (cobalt hematoporphyrin [Co-HP]), which resulted in an
      inhibitory potency much stronger than that of H2-PP. Surface plasmon resonance
      analysis and molecular docking study showed that Co-HP binds directly to CLEC-2
      at N120, N210, and K211, previously unknown podoplanin-binding sites; this
      binding was confirmed by analysis of CLEC-2 mutants with alterations in N120
      and/or K211. Co-HP at a concentration of 1.53 MUM inhibited platelet aggregation
      mediated through CLEC-2, but not that mediated through other receptors. IV
      administration of Co-HP to mice significantly inhibited hematogenous metastasis
      of podoplanin-expressing B16F10 cells to the lung as well as in vivo arterial and
      venous thrombosis, without a significant increase in tail-bleeding time. Thus, Co
      HP may be a promising molecule for antimetastatic and antiplatelet treatment that
      does not cause bleeding tendency.

PMID- 30190285
TI  - How to do it: the clinicopathological conference.
AB  - The prime purpose of the clinicopathological conference (CPC) is education,
      delivered ideally in an entertaining and engaging manner. This article tackles
      both how to organise a CPC (more challenging than it might appear) and how to
      survive as a CPC discussant (always challenging). The patient at the heart of the
      CPC will have had a challenging and difficult illness. The reanalysis of the
      clinical presentation by the discussant, a re-exploration of their clinical
      journey, is the key to the educational value of the CPC rather than the ultimate
      diagnosis. A well-delivered CPC is the pinnacle of educational events in
      neurology, and this article highlights some useful tips on both sides of the
      divide.

PMID- 30190284
TI  - Targeting amino acids metabolic profile to identify novel metabolic
      characteristics in atrial fibrillation.
AB  - Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia whose
      incidence is on the rise globally. However, the pathophysiologic mechanism of AF
      remains poorly understood and there has been a lack of circulatory markers to
      diagnose and predict prognosis of AF. In the present study, by measuring
      metabolic profile and analyzing plasma amino acid levels in AF patients, we
      sought to determine whether amino acid metabolism was correlated to the
      occurrence of AF. Methods: Consecutive patients admitted to hospital for AF were
      enrolled. Plasma samples were obtained after overnight fast and a profile of 61
      amino acids was then measured using gas chromatography/mass spectrometry (GC/MS).
      Results: Twenty-three AF and thirty-seven control patients were enrolled in the
      study. A number of plasma amino acids were altered in AF, which showed
      significant prediction value for AF. Intriguingly, circulating 4
      hydroxypyrrolidine-2-carboxylic was gradually lowered with the persistence of AF.
      Plasma amino acid levels were more strongly correlated with each other in AF as
      compared with control. Conclusion: By utilizing non-target metabolic profile
      surveys, we have found a number of altered amino acids, which exhibit diagnostic
      value for AF. Enhanced amino acids correlation network further identified AF as a
      metabolism disorder.

PMID- 30190286
TI  - Cytomatrix proteins CAST and ELKS regulate retinal photoreceptor development and
      maintenance.
AB  - At the presynaptic active zone (AZ), the related cytomatrix proteins CAST and
      ELKS organize the presynaptic release machinery. While CAST is known to regulate
      AZ size and neurotransmitter release, the role of ELKS and the integral system of
      CAST/ELKS together is poorly understood. Here, we show that CAST and ELKS have
      both redundant and unique roles in coordinating synaptic development, function,
      and maintenance of retinal photoreceptor ribbon synapses. A CAST/ELKS double
      knockout (dKO) mouse showed high levels of ectopic synapses and reduced responses
      to visual stimulation. Ectopic formation was not observed in ELKS conditional KO
      but progressively increased with age in CAST KO mice with higher rates in the
      dKO. Presynaptic calcium influx was strongly reduced in rod photoreceptors of
      CAST KO and dKO mice. Three-dimensional scanning EM reconstructions showed
      structural abnormalities in rod triads of CAST KO and dKO. Remarkably, AAV
      mediated acute ELKS deletion after synapse maturation induced neurodegeneration
      and loss of ribbon synapses. These results suggest that CAST and ELKS work in
      concert to promote retinal synapse formation, transmission, and maintenance.

PMID- 30190287
TI  - Sox12 promotes T reg differentiation in the periphery during colitis.
AB  - Peripherally induced regulatory T (pT reg) cells play indispensable roles in
      regulating gut inflammation; however, the mechanism underling the differentiation
      of pT reg cells under inflammatory conditions remains largely unknown. Here, we
      show that the expression of Sox12, a member of SoxC family, is significantly
      induced in T reg cells in colitic mice. We also show that TCR-NFAT signaling
      induces Sox12 expression in CD4+ T cells. Although Sox12 is not required for the
      development of thymus-derived T reg (tT reg) cells, Sox12 is involved in the
      development of pT reg cells under inflammatory conditions in an adoptive transfer
      colitis model. Moreover, we found that enforced expression of Sox12 is sufficient
      to promote Foxp3 expression in CD4+ T cells even in the absence of TGF-beta or IL
      2 and that Sox12 binds to Foxp3 promoter and drives its transcription. These
      results suggest that TCR-NFAT signaling induces the development of pT reg cells
      in colitic mice partly through Sox12 induction.

PMID- 30190289
TI  - Consumer-based technology can enhance hypertension control.

PMID- 30190290
TI  - Collaborative program spurs process improvements.

PMID- 30190292
TI  - Implementing i.v. push administration of piperacillin-tazobactam in response to
      shortage of small-volume infusion bags.

PMID- 30190293
TI  - Noninsulin medication therapy for hospitalized patients with diabetes mellitus.
AB  - PURPOSE: Published evidence regarding the role of noninsulin antidiabetic
      therapies in glycemic management of hospitalized patients with diabetes mellitus
      is reviewed. SUMMARY: The American Diabetes Association recommends against the
      routine use of noninsulin antidiabetic therapies during hospitalization and
      supports insulin use instead. There are significant risks associated with insulin
      therapy, including hypoglycemia, and use of alternative therapies may be
      considered in hospitalized patients. A MEDLINE literature search was conducted to
      find articles on studies evaluating the use of noninsulin antidiabetic therapies
      in the inpatient setting; all full-text English-language publications presenting
      observational and randomized clinical trial data on the topic of interest were
      considered for inclusion in the review, with 9 publications selected for review.
      The majority of the reviewed research focused on incretin-based therapies, and
      favorable safety and efficacy outcomes were reported with the use of dipeptidyl
      peptidase-4 (DPP-4) inhibitors. The available evidence indicates that the use of
      other noninsulin medications, including glucagon-like peptide-1 receptor agonists
      and sulfonylureas, to achieve and maintain glycemic control in the inpatient
      setting may be limited by adverse effects. CONCLUSION: Optimal glycemic control
      in hospitalized patients with diabetes is necessary to avoid adverse effects.
      Insulin therapy is currently the primary medication recommended for this patient
      population. DPP-4 inhibitors have been demonstrated to be safe and effective for
      use in the inpatient setting in patients with well-controlled diabetes. Further
      research is needed to help define the role of noninsulin medications in the
      inpatient setting.

PMID- 30190288
TI  - Remote ischemic post-conditioning promotes hematoma resolution via AMPK-dependent
      immune regulation.
AB  - Spontaneous intracerebral hemorrhage (ICH) produces the highest acute mortality
      and worst outcomes of all stroke subtypes. Hematoma volume is an independent
      determinant of ICH patient outcomes, making clot resolution a primary goal of
      clinical management. Herein, remote-limb ischemic post-conditioning (RIC), the
      repetitive inflation-deflation of a blood pressure cuff on a limb, accelerated
      hematoma resolution and improved neurological outcomes after ICH in mice.
      Parabiosis studies revealed RIC accelerated clot resolution via a humoral
      mediated mechanism. Whereas RIC increased anti-inflammatory macrophage
      activation, myeloid cell depletion eliminated the beneficial effects of RIC after
      ICH. Myeloid-specific inactivation of the metabolic regulator, AMPKalpha1,
      attenuated RIC-induced anti-inflammatory macrophage polarization and delayed
      hematoma resolution, providing a molecular link between RIC and immune
      activation. Finally, chimera studies implicated myeloid CD36 expression in RIC
      mediated neurological recovery after ICH. Thus, RIC, a clinically well-tolerated
      therapy, noninvasively modulates innate immune responses to improve ICH outcomes.
      Moreover, immunometabolic changes may provide pharmacodynamic blood biomarkers to
      clinically monitor the therapeutic efficacy of RIC.

PMID- 30190294
TI  - Nimodipine for the treatment of otolaryngic indications.
AB  - PURPOSE: The uses of nimodipine for otolaryngic indications are reviewed, and
      recommendations for its use in clinical practice are provided. SUMMARY:
      Nimodipine is currently indicated for the improvement of neurologic outcomes in
      adult patients with aneurysmal subarachnoid hemorrhage (aSAH). However, other
      oral and i.v. calcium channel blockers have not exhibited the same beneficial
      effects in patients with aSAH, leading clinicians to believe that nimodipine
      possesses unique neuroprotective effects in addition to its calcium channel
      blocking and vasodilatory properties. Consequently, clinical investigations of
      nimodipine have been conducted for cochlear and facial nerve preservation after
      vestibular schwannoma (VS) surgery, symptomatic management of Meniere's disease
      and peripheral vertigo, and recovery of vocal cord paralysis after laryngeal
      nerve injury. Three prospective randomized studies have investigated nimodipine
      for hearing and/or nerve preservation in patients undergoing VS resection, the
      results of which have suggested a potential benefit of initiating nimodipine
      during the perioperative period. Several studies of Meniere's disease and/or
      peripheral vertigo have reported improved symptom control with nimodipine. For
      vocal fold paralysis associated with recurrent laryngeal nerve (RLN) injury,
      nimodipine may increase the recovery rate based on the results of 1 nonrandomized
      prospective study that used nimodipine in a protocolized manner. One small pilot
      study found that nimodipine improved facial nerve function after maxillofacial
      surgery. CONCLUSION: Due to its proposed vasoactive and neuroprotective effects,
      nimodipine may play a role in the treatment of a number of otolaryngic
      pathologies including VS, Meniere's disease, peripheral vertigo, RLN injury, and
      facial weakness after maxillofacial surgery. Small studies have shown improved
      symptom control and recovery after surgery. Since all of the aforementioned
      indications are still considered off label, clinicians and patients should
      collaboratively assess the risks and benefits before initiating treatment.

PMID- 30190295
TI  - Predictors of oversedation in hospitalized patients.
AB  - PURPOSE: Results of a study to determine demographic and clinical characteristics
      predictive of oversedation and potential opioid-induced respiratory depression
      (OIRD) in hospitalized patients are reported. METHODS: In a retrospective case
      controlled study, an incident reporting database was searched to identify cases
      of in-hospital oversedation; to form the control group, patients who did not
      experience an oversedation event while hospitalized were sampled in reverse
      chronological order until the desired total sample size (n = 225) was obtained.
      An allocation ratio of 2:1 was specified to adjust for case variability. Binary
      logistic regression was employed to identify factors predictive of oversedation.
      RESULTS: Female sex (odds ratio [OR], 2.41; 95% confidence interval [CI], 1.05
      5.50), comorbid renal disease (OR, 4.22; 95% CI, 1.66-10.70), untreated sleep
      apnea (OR, 32.32; 95% CI, 2.72-384.72), receipt of long-acting oxycodone (OR,
      4.76; 95% CI, 1.70-13.33), and as-needed use of hydromorphone (OR, 2.73; 95% CI,
      1.19-6.27) were significant predictors of oversedation; as-needed analgesia
      administered by the oral route (OR, 0.16; 95% CI, 0.07-0.36) or i.v. route (OR,
      0.33; 95% CI, 0.14-0.80) had a significant protective effect. The final
      prediction model explained 47.8% of variance in oversedation risk and was found
      to have strong discriminatory performance. CONCLUSION: The identified risk
      factors for oversedation and potential OIRD in hospitalized patients can form the
      basis of quality-improvement initiatives to prevent oversedation through improved
      prescribing and patient monitoring.

PMID- 30190297
TI  - Getting more health from healthcare: quality improvement must acknowledge patient
      coproduction-an essay by Paul Batalden.

PMID- 30190296
TI  - The Cleveland Clinic Pharmacy Population Health Management Summit.

PMID- 30190298
TI  - Lifetime history of sexual and physical abuse among competitive athletics (track
      and field) athletes: cross sectional study of associations with sports and non
      sports injury.
AB  - OBJECTIVE: To examine associations between lifetime sexual and physical abuse,
      and the likelihood of injury within and outside sport in athletes involved in
      competitive athletics. METHODS: A cross sectional study was performed among the
      top 10 Swedish athletics athletes using 1 year prevalence of sports and non
      sports injuries as the primary outcome measure. Associations with
      sociodemographic characteristics, lifetime abuse history and training load were
      investigated. Data were analysed using simple and multiple logistic regression
      models. RESULTS: 11% of 197 participating athletes reported lifetime sexual
      abuse; there was a higher proportion of women (16.2%) than men (4.3%) (P=0.005).
      18% reported lifetime physical abuse; there was a higher proportion of men
      (22.8%) than women (14.3%) (P=0.050). For women, lifetime sexual abuse was
      associated with an increased likelihood of a non-sports injury (OR 8.78, CI 2.76
      to 27.93; P<0.001). Among men, increased likelihood of a non-sports injury was
      associated with more frequent use of alcoholic beverages (OR 6.47, CI 1.49 to
      28.07; P=0.013), while commencing athletics training at >13 years of age was
      associated with a lower likelihood of non-sports injury (OR 0.09, CI 0.01 to
      0.81; P=0.032). Lifetime physical abuse was associated with a higher likelihood
      of sports injury in women (OR 12.37, CI 1.52 to 100.37; P=0.019). Among men,
      athletes with each parents with <=12 years formal education had a lower
      likelihood of sustaining an injury during their sports practice (OR 0.37, CI 0.14
      to 0.96; P=0.040). CONCLUSIONS: Lifetime sexual and physical abuse were
      associated with an increased likelihood of injury among female athletes.
      Emotional factors should be included in the comprehension of injuries sustained
      by athletes.

PMID- 30190299
TI  - Regorafenib for Patients with Metastatic Colorectal Cancer Who Progressed After
      Standard Therapy: Results of the Large, Single-Arm, Open-Label Phase IIIb CONSIGN
      Study.
AB  - BACKGROUND: In the phase III CORRECT trial, regorafenib significantly improved
      survival in treatment-refractory metastatic colorectal cancer (mCRC). The CONSIGN
      study was designed to further characterize regorafenib safety and allow patients
      access to regorafenib before market authorization. METHODS: This prospective,
      single-arm study enrolled patients in 25 countries at 186 sites. Patients with
      treatment-refractory mCRC and an Eastern Cooperative Oncology Group performance
      status (ECOG PS) <=1 received regorafenib 160 mg once daily for the first 3 weeks
      of each 4-week cycle. The primary endpoint was safety. Progression-free survival
      (PFS) per investigator assessment was the only efficacy evaluation. RESULTS: In
      total, 2,872 patients were assigned to treatment and 2,864 were treated. Median
      age was 62 years, ECOG PS 0/1 was 47%/53%, and 74% had received at least three
      prior regimens for metastatic disease. Median treatment duration was three
      cycles. Treatment-emergent adverse events (TEAEs) led to dose reduction in 46% of
      patients. Regorafenib-related TEAEs led to treatment discontinuation in 9%. Grade
      5 regorafenib-related TEAEs occurred in <1%. The most common grade >=3
      regorafenib-related TEAEs were hypertension (15%), hand-foot skin reaction (14%),
      fatigue (13%), diarrhea (5%), and hypophosphatemia (5%). Treatment-emergent grade
      3-4 laboratory toxicities included alanine aminotransferase (6%), aspartate
      aminotransferase (7%), and bilirubin (13%). Ongoing monitoring identified one
      nonfatal case of regorafenib-related severe drug-induced liver injury per DILI
      Working Group criteria. Median PFS (95% confidence interval [CI]) was 2.7 months
      (2.6-2.7). CONCLUSION: In CONSIGN, the frequency and severity of TEAEs were
      consistent with the known safety profile of regorafenib. PFS was similar to
      reports of phase III trials. ClinicalTrials.gov: NCT01538680. IMPLICATIONS FOR
      PRACTICE: Patients with metastatic colorectal cancer (mCRC) who fail treatment
      with standard therapies, including chemotherapy and monoclonal antibodies
      targeting vascular endothelial growth factor or epidermal growth factor receptor,
      have few treatment options. The multikinase inhibitor regorafenib was shown to
      improve survival in patients with treatment-refractory mCRC in the phase III
      CORRECT (N = 760) and CONCUR (N = 204) trials. However, safety data on
      regorafenib for mCRC in a larger number of patients were not available. The
      CONSIGN trial, carried out prospectively in more than 2,800 patients across 25
      countries, confirmed the safety profile of regorafenib from the phase III trials
      and reinforced the importance of using treatment modifications to manage adverse
      events.

PMID- 30190300
TI  - "I need to know what makes somebody tick ...": Challenges and Strategies of
      Implementing Shared Decision-Making in Individualized Oncology.
AB  - BACKGROUND: Shared decision-making (SDM) has been advocated as an ethical
      framework for decision-making in cancer care. According to SDM, patients make
      decisions in light of their values and based on the available evidence. However,
      SDM is difficult to implement in cancer care. A lack of applicability in practice
      is often reported. This empirical-ethical study explores factors potentially
      relevant to current difficulties in translating the concept of SDM into clinical
      practice. METHODS: This study was conducted with nonparticipant observation of
      the decision-making process in patients with gastrointestinal cancers for whom
      the benefit of adjuvant chemotherapy was uncertain according to clinical
      guidelines. Triangulation of qualitative data analysis was conducted by means of
      semistructured interviews subsequent to the observation. Observation notes and
      interview transcripts were analyzed according to the principles of grounded
      theory. RESULTS: Deviating from the concept of SDM, oncologists initiated a
      process of eliciting values and medical information prior to conveying
      information. The purpose of this approach was to select and individualize
      information relevant to the treatment decision. In doing so, the oncologists
      observed used two strategies: "biographical communication" and a
      "metacommunicative approach." Both strategies could be shown to be effective or
      to fail depending on patients' characteristics such as their view of the
      physicians' role and the relevance of value-related information for medical
      decision-making. CONCLUSION: In contrast to the conceptual account of SDM,
      oncologists are in need of patient-related information prior to conveying
      information. Both strategies observed to elicit such information are in principle
      justifiable but need to be adapted in accordance with patient preferences and
      decision-making styles. IMPLICATIONS FOR PRACTICE: This study showed that
      knowledge of patients' values and preferences is very important to properly adapt
      the giving of medical information and to further the process of shared decision
      making. Shared decision-making (SDM) trainings should consider different
      strategies of talking about values. The right strategy depends largely on the
      patient's preferences in communication. To be aware of the role of values in SDM
      and to be able to switch communicative strategies might prove to be of particular
      value. A more systematic evaluation of the patient's decision-making preferences
      as part of routine procedures in hospitals might help to reduce value-related
      barriers in communication.

PMID- 30190301
TI  - Minimal Increase in Survival Throughout the Years in Patients with Soft Tissue
      Sarcoma with Synchronous Metastases: Results of a Population-Based Study.
AB  - BACKGROUND: Treatment options for patients with metastatic soft tissue sarcoma
      (STS) have increased in the last decade. We aimed to examine whether this is
      associated with improved overall survival (OS) in patients with STS with
      synchronous metastases. PATIENTS AND METHODS: Patients diagnosed with STS and
      synchronous metastases from 1989 to 2014 were queried from The Netherlands Cancer
      Registry. Trends in OS were assessed by the Kaplan-Meier method and log-rank test
      in time intervals of 5 years, for the whole study population and in subgroups for
      liposarcomas, leiomyosarcoma, and other STS subtypes. A multivariable Cox
      regression analysis was performed to identify characteristics prognostic for OS.
      RESULTS: Median OS of the 1,393 identified patients did not improve significantly
      over the years from 5.8 months in 1989-1994 to 8.1 months in 2010-2014, but there
      was an evident trend. Median OS was prolonged in the subgroups of liposarcomas
      (3.6 to 9.3 months), leiomyosarcomas (11.3 to 14.6 months), and other STS
      subtypes (5.7 to 6.3 months), although there were no significant improvements in
      OS over the years. Primary tumor site in one of the extremities and surgery in an
      academic center had a favorable effect on OS, whereas significant negative
      predictors were no treatment, elderly age, STS subtype other than liposarcoma or
      leiomyosarcoma, high or unknown grade, and nodal involvement. CONCLUSION:
      Although overall survival of patients with STS with synchronous metastases in
      this nationwide and "real-life" population has improved over the years, the
      improvement was not statistically significant, despite new treatment options.
      IMPLICATIONS FOR PRACTICE: Treatment of patients with metastatic soft tissue
      sarcoma (STS) has changed in the past years, with new drugs such as trabectedin
      (2007) and pazopanib (2012) becoming available. By using data from the nationwide
      Netherlands Cancer Registry, the impact of these changes in treatment policies on
      survival is analyzed in a "real-life" population of patients with STS with
      synchronous metastases, rather than in a strictly selected trial population.
      Unfortunately, overall survival improved only minimally and not significantly for
      these patients diagnosed from 1989 to 2014. Hopefully, the advent of novel
      treatment options, such as eribulin and olaratumab, will further improve the
      outcome of this patient group.

PMID- 30190302
TI  - An Open Label Phase Ib Dose Escalation Study of TRC105 (Anti-Endoglin Antibody)
      with Axitinib in Patients with Metastatic Renal Cell Carcinoma.
AB  - BACKGROUND: TRC105 is an IgG1 endoglin monoclonal antibody that potentiates VEGF
      inhibitors in preclinical models. We assessed safety, pharmacokinetics, and
      antitumor activity of TRC105 in combination with axitinib in patients with
      metastatic renal cell carcinoma (mRCC). SUBJECTS, MATERIALS, AND METHODS: Heavily
      pretreated mRCC patients were treated with TRC105 weekly (8 mg/kg and then 10
      mg/kg) in combination with axitinib (initially at 5 mg b.i.d. and then escalated
      per patient tolerance to a maximum of 10 mg b.i.d.) until disease progression or
      unacceptable toxicity using a standard 3 + 3 phase I design. RESULTS: Eighteen
      patients (median number of prior therapies = 3) were treated. TRC105 dose
      escalation proceeded to 10 mg/kg weekly without dose-limiting toxicity. Adverse
      event characteristics of each drug were not increased in frequency or severity
      when the two drugs were administered concurrently. TRC105 and axitinib
      demonstrated preliminary evidence of activity, including partial responses (PR)
      by RECIST in 29% of patients, and median progression-free survival (11.3 months).
      None of the patients with PR had PR to prior first-line treatment. Lower baseline
      levels of osteopontin and higher baseline levels of TGF-beta receptor 3
      correlated with overall response rate. CONCLUSION: TRC105 at 8 and 10 mg/kg
      weekly was well tolerated in combination with axitinib, with encouraging evidence
      of activity in patients with mRCC. A multicenter, randomized phase II trial of
      TRC105 and axitinib has recently completed enrollment (NCT01806064). IMPLICATIONS
      FOR PRACTICE: TRC105 is a monoclonal antibody to endoglin (CD105), a receptor
      densely expressed on proliferating endothelial cells and also on renal cancer
      stem cells that is implicated as a mediator of resistance to inhibitors of the
      VEGF pathway. In this Phase I trial, TRC105 combined safely with axitinib at the
      recommended single agent doses of each drug in patients with renal cell
      carcinoma. The combination demonstrated durable activity in a VEGF inhibitor
      refractory population and modulated several angiogenic biomarkers. A randomized
      Phase II trial testing TRC105 in combination with axitinib in clear cell renal
      cell carcinoma has completed accrual.

PMID- 30190303
TI  - Follow-Up of Lesions with Equivocal Radiotracer Uptake on PSMA-Targeted PET in
      Patients with Prostate Cancer: Predictive Values of the PSMA-RADS-3A and PSMA
      RADS-3B Categories.
AB  - Purpose: Prostate-specific membrane antigen (PSMA)-targeted positron emission
      tomography (PET) imaging has become commonly utilized in patients with prostate
      cancer (PCa). The PSMA reporting and data system version 1.0 (PSMA-RADS version
      1.0) categorizes lesions on the basis of the likelihood of PCa involvement, with
      PSMA-RADS-3A (soft tissue) and PSMA-RADS-3B (bone) lesions being indeterminate
      for the presence of disease. We retrospectively reviewed the imaging follow-up of
      such lesions to determine the rate at which they underwent changes suggestive of
      underlying PCa. Methods: PET/CT imaging with 18F-DCFPyL was carried out in 110
      patients with PCa and lesions were categorized according to PSMA-RADS Version
      1.0. 56/110 (50.9%) patients were determined to have indeterminate PSMA-RADS-3A
      or PSMA-RADS-3B lesions and 22/56 (39.3%) patients had adequate follow-up to be
      included in the analysis. The maximum standardized uptake values (SUVmax) of the
      lesions were obtained and the ratios of SUVmax of the lesions to SUVmean of blood
      pool (SUVmax-lesion/SUVmean-bloodpool) were calculated. Pre-determined criteria
      were used to evaluate the PSMA-RADS-3A and PSMA-RADS-3B lesions on follow-up
      imaging to determine if they demonstrated evidence of underlying malignancy.
      Results: A total of 46 lesions in 22 patients were considered indeterminate for
      PCa (i.e. PSMA-RADS-3A (32 lesions) or PSMA-RADS-3B (14 lesions)) and were
      evaluable on follow-up imaging. 27/46 (58.7%) lesions demonstrated changes on
      follow-up imaging consistent with the presence of underlying PCa at baseline.
      These lesions included 24/32 (75.0%) PSMA-RADS-3A lesions and 3/14 (21.4%)
      lesions categorized as PSMA-RADS-3B. The ranges of SUVmax and SUVmax
      lesion/SUVmean-bloodpool overlapped between those lesions demonstrating changes
      consistent with malignancy on follow-up imaging and those lesions that remained
      unchanged on follow-up. Conclusion: PSMA-RADS-3A and PSMA-RADS-3B lesions are
      truly indeterminate in that proportions of findings in both categories
      demonstrate evidence of malignancy on follow-up imaging. Overall, PSMA-RADS-3A
      lesions are more likely than PSMA-RADS-3B lesions to represent sites of PCa and
      this information should be taken into account when guiding patient therapy.

PMID- 30190305
TI  - Amyloid Load - a more sensitive biomarker for amyloid imaging.
AB  - Amyloid-beta (Abeta) plays a key role in the pathogenesis of Alzheimer's disease
      (AD) and it can be imaged in vivo using [18F]-AV45 positron emission tomography
      (PET). The mean cortical standardised uptake value ratio (SUVr) is a commonly
      used outcome measure for quantifying the global Abeta burden however the
      sensitivity is sub-optimal which can lead to low power in clinical trials. We
      introduce amyloid load, AbetaL as a novel biomarker to quantify the global Abeta
      burden along with an automated algorithm for its calculation (IQA). AbetaL is
      evaluated on cross-sectional and longitudinal data obtained from the Alzheimer's
      disease neuroimaging initiative (ADNI). The cross-sectional data consisted of 769
      subjects across the disease spectrum (211 healthy controls (HC), 223 early mild
      cognitive impairment (EMCI), 204 late mild cognitive impairment (LMCI), 132 AD).
      The distributions of in the four different classifications were compared and the
      same analyses were applied to the mean cortical SUVr outcome measure. The effect
      sizes (hedges' g) between all classifications were higher for AbetaL than mean
      cortical SUVr with the mean difference in effect size being 56%. 147 of the EMCI
      patients had a two-year follow-up scan and the effect size between baseline and
      follow-up for was 0.49 compared to 0.35 for mean cortical SUVr demonstrating an
      equivalent increase in power for longitudinal data. These results provide
      evidence that AbetaL will be a valuable outcome measure in future Abeta imaging
      studies providing an substantial increase in power over currently employed SUVr
      methods.

PMID- 30190304
TI  - Interobserver Agreement for the Standardized Reporting System PSMA-RADS 1.0 on
      18F-DCFPyL PET/CT Imaging.
AB  - Recently, the standardized reporting and data system for prostate-specific
      membrane antigen (PSMA)-targeted PET imaging studies, termed PSMA-RADS version
      1.0, was introduced. We aimed to determine the interobserver agreement for
      applying PSMA-RADS to imaging interpretation of 18F-DCFPyL (2-(3-{1-carboxy-5-[(6
      18F-fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid) PET
      examinations in a prospective setting mimicking the typical clinical workflow at
      a prostate cancer referral center. Methods: Four readers (2 experienced readers
      (ERs, >3 y of PSMA-targeted PET interpretation experience) and 2 inexperienced
      readers (IRs, <1 y of experience)), who had all read the initial publication on
      PSMA-RADS 1.0, assessed 50 18F-DCFPyL PET/CT studies independently. Per scan, a
      maximum of 5 target lesions was selected by the observers, and a PSMA-RADS score
      for every target lesion was recorded. No specific preexisting conditions were
      placed on the selection of the target lesions, although PSMA-RADS 1.0 suggests
      that readers focus on the most avid or largest lesions. An overall scan
      impression based on PSMA-RADS was indicated, and interobserver agreement rates on
      a target lesion-based, on an organ-based, and on an overall PSMA-RADS score-based
      level were computed. Results: The number of target lesions identified by each
      observer was as follows: ER 1, 123; ER 2, 134; IR 1, 123; and IR 2, 120. Among
      those selected target lesions, 125 were chosen by at least 2 individual observers
      (all 4 readers selected the same target lesion in 58 of 125 [46.4%] instances, 3
      readers in 40 of 125 [32%], and 2 observers in 27 of 125 [21.6%]). The
      interobserver agreement for PSMA-RADS scoring among identical target lesions was
      good (intraclass correlation coefficient [ICC] for 4, 3, and 2 identical target
      lesions, >=0.60, respectively). For lymph nodes, an excellent interobserver
      agreement was derived (ICC, 0.79). The interobserver agreement for an overall
      scan impression based on PSMA-RADS was also excellent (ICC, 0.84), with a
      significant difference for ER (ICC, 0.97) vs. IR (ICC, 0.74) (P = 0.005).
      Conclusion: PSMA-RADS demonstrated a high concordance rate in this study, even
      among readers with different levels of experience. This finding suggests that
      PSMA-RADS can be effectively used for communication with clinicians and can be
      implemented in the collection of data for large prospective trials.

PMID- 30190306
TI  - Current treatment strategies in metastasized differentiated thyroid cancer.
AB  - On successful completion of this activity one should be able to (1) judge the
      prognosis of patients harboring metastasized differentiated thyroid cancer (2)
      identify suitable treatment regimens taking into account the characteristics of
      the tumor and the patient's general condition, (3) know the basics of radioiodine
      treatment, TKI treatment and redifferentiation treatment for metastasized DTC.

PMID- 30190307
TI  - Systematic discovery of natural CRISPR-Cas12a inhibitors.
AB  - Cas12a (Cpf1) is a CRISPR-associated nuclease with broad utility for synthetic
      genome engineering, agricultural genomics, and biomedical applications. Although
      bacteria harboring CRISPR-Cas9 or CRISPR-Cas3 adaptive immune systems sometimes
      acquire mobile genetic elements encoding anti-CRISPR proteins that inhibit Cas9,
      Cas3, or the DNA-binding Cascade complex, no such inhibitors have been found for
      CRISPR-Cas12a. Here we use a comprehensive bioinformatic and experimental
      screening approach to identify three different inhibitors that block or diminish
      CRISPR-Cas12a-mediated genome editing in human cells. We also find a widespread
      connection between CRISPR self-targeting and inhibitor prevalence in prokaryotic
      genomes, suggesting a straightforward path to the discovery of many more anti
      CRISPRs from the microbial world.

PMID- 30190308
TI  - Discovery of widespread type I and type V CRISPR-Cas inhibitors.
AB  - Bacterial CRISPR-Cas systems protect their host from bacteriophages and other
      mobile genetic elements. Mobile elements, in turn, encode various anti-CRISPR
      (Acr) proteins to inhibit the immune function of CRISPR-Cas. To date, Acr
      proteins have been discovered for type I (subtypes I-D, I-E, and I-F) and type II
      (II-A and II-C) but not other CRISPR systems. Here, we report the discovery of 12
      acr genes, including inhibitors of type V-A and I-C CRISPR systems. AcrVA1
      inhibits a broad spectrum of Cas12a (Cpf1) orthologs-including MbCas12a,
      Mb3Cas12a, AsCas12a, and LbCas12a-when assayed in human cells. The acr genes
      reported here provide useful biotechnological tools and mark the discovery of acr
      loci in many bacteria and phages.

PMID- 30190309
TI  - Structure of the human voltage-gated sodium channel Nav1.4 in complex with beta1.
AB  - Voltage-gated sodium (Nav) channels, which are responsible for action potential
      generation, are implicated in many human diseases. Despite decades of rigorous
      characterization, the lack of a structure of any human Nav channel has hampered
      mechanistic understanding. Here, we report the cryo-electron microscopy structure
      of the human Nav1.4-beta1 complex at 3.2-A resolution. Accurate model building
      was made for the pore domain, the voltage-sensing domains, and the beta1 subunit,
      providing insight into the molecular basis for Na+ permeation and kinetic
      asymmetry of the four repeats. Structural analysis of reported functional
      residues and disease mutations corroborates an allosteric blocking mechanism for
      fast inactivation of Nav channels. The structure provides a path toward
      mechanistic investigation of Nav channels and drug discovery for Nav
      channelopathies.

PMID- 30190310
TI  - Dimerization quality control ensures neuronal development and survival.
AB  - Aberrant complex formation by recurrent interaction modules, such as BTB domains,
      leucine zippers, or coiled coils, can disrupt signal transduction, yet whether
      cells detect and eliminate complexes of irregular composition is unknown. By
      searching for regulators of the BTB family, we discovered a quality control
      pathway that ensures functional dimerization [dimerization quality control
      (DQC)]. Key to this network is the E3 ligase SCFFBXL17, which selectively binds
      and ubiquitylates BTB dimers of aberrant composition to trigger their clearance
      by proteasomal degradation. Underscoring the physiological importance of DQC,
      SCFFBXL17 is required for the differentiation, function, and survival of neural
      crest and neuronal cells. We conclude that metazoan organisms actively monitor
      BTB dimerization, and we predict that distinct E3 ligases similarly control
      complex formation by other recurrent domains.

PMID- 30190313
TI  - A man with fever and haemoglobinuria after blood transfusion.

PMID- 30190311
TI  - Aptamer-field-effect transistors overcome Debye length limitations for small
      molecule sensing.
AB  - Detection of analytes by means of field-effect transistors bearing ligand
      specific receptors is fundamentally limited by the shielding created by the
      electrical double layer (the "Debye length" limitation). We detected small
      molecules under physiological high-ionic strength conditions by modifying printed
      ultrathin metal-oxide field-effect transistor arrays with deoxyribonucleotide
      aptamers selected to bind their targets adaptively. Target-induced conformational
      changes of negatively charged aptamer phosphodiester backbones in close proximity
      to semiconductor channels gated conductance in physiological buffers, resulting
      in highly sensitive detection. Sensing of charged and electroneutral targets
      (serotonin, dopamine, glucose, and sphingosine-1-phosphate) was enabled by
      specifically isolated aptameric stem-loop receptors.

PMID- 30190314
TI  - Insect fat body cell morphology and response to cold stress is modulated by
      acclimation.
AB  - Mechanistic understanding about the nature of cellular cryoinjury and mechanisms
      by which some animals survive freezing while others do not is currently lacking.
      Here, we exploited the broadly manipulable freeze tolerance of larval malt flies
      (Chymomyza costata) to uncover cell and tissue morphological changes associated
      with freeze mortality. Diapause induction, cold acclimation and dietary proline
      supplementation generate malt fly variants ranging from weakly to extremely
      freeze tolerant. Using confocal microscopy and immunostaining of the fat body,
      Malpighian tubules and anterior midgut, we described tissue and cytoskeletal (F
      actin and alpha-tubulin) morphologies among these variants after exposure to
      various cold stresses (from chilling at -5 degrees C to extreme freezing at -196
      degrees C), and upon recovery from cold exposure. Fat body tissue appeared to be
      the most susceptible to cryoinjury: freezing caused coalescence of lipid
      droplets, loss of alpha-tubulin structure and apparent aggregation of F-actin. A
      combination of diapause and cold acclimation substantially lowered the
      temperature at which these morphological disruptions occurred. Larvae that
      recovered from a freezing challenge repaired F-actin aggregation but not lipid
      droplet coalescence or alpha-tubulin structure. Our observations indicate that
      lipid coalescence and damage to alpha-tubulin are non-lethal forms of freeze
      injury, and suggest that repair or removal (rather than protection) of actin
      proteins is a potential mechanism of acquired freeze tolerance.

PMID- 30190315
TI  - No short-term physiological costs of offspring care in a cooperatively breeding
      bird.
AB  - The cost of reproduction results in a life-history trade-off where investment in
      current reproduction via costly parental care decreases subsequent fitness.
      Although this trade-off is thought to occur ubiquitously across animals, there is
      equivocal evidence that parental care behaviours are costly. A major challenge of
      studying the cost of parental care has been a lack of consensus over which
      physiological mechanisms underlie this trade-off. Here, we compare four traits
      believed to mediate the cost of parental care by examining whether
      glucocorticoids, oxidative stress, immune function or body condition represent a
      cost of performing offspring care and shape subsequent fitness. We use a 4 year
      dataset collected in free-living cooperatively breeding superb starlings
      (Lamprotornis superbus), a species in which parental and alloparental care effort
      varies widely among individuals and across years. Our results showed that within
      individual change in physiology was unrelated to investment in offspring care,
      and physiological state during chick rearing did not predict the likelihood that
      an individual would breed in subsequent seasons. Instead, individuals that had
      elevated baseline corticosterone during incubation performed more nest guarding,
      suggesting that this hormone may play a preparatory role for investing in
      offspring care. Together, our results indicate that superb starlings modify their
      investment in offspring care according to their physiological state during
      incubation, despite there being no evidence of a short-term physiological cost of
      parental or alloparental care. Thus, breeding cooperatively appears to provide
      individuals with the flexibility to adjust their investment in offspring care and
      overcome any potential costs of reproduction.

PMID- 30190317
TI  - Physiological responses of ionotropic histamine receptors, PxHCLA and PxHCLB, to
      neurotransmitter candidates in a butterfly, Papilio xuthus.
AB  - Histamine is the only known neurotransmitter released by arthropod
      photoreceptors. Synaptic transmission from photoreceptors to second-order neurons
      is mediated by the activation of histamine-gated chloride channels (HCLs). These
      histaminergic synapses have been assumed to be conserved among insect visual
      systems. However, our understanding of the channels in question has thus far been
      based on studies in flies. In the butterfly Papilio xuthus, we have identified
      two candidate histamine-gated chloride channels, PxHCLA and PxHCLB, and studied
      their physiological properties using a whole-cell patch-clamp technique. We
      studied the responses of channels expressed in cultured cells to histamine as
      well as to other neurotransmitter candidates, namely GABA, tyramine, serotonin, d
      /l-glutamate and glycine. We found that histamine and GABA activated both PxHCLA
      and PxHCLB, while the other molecules did not. The sensitivity to histamine and
      GABA was consistently higher in PxHCLB than in PxHCLA. Interestingly,
      simultaneous application of histamine and GABA activated both PxHCLA and PxHCLB
      more strongly than either neurotransmitter individually; histamine and GABA may
      have synergistic effects on PxHCLs in the regions where they co-localize. Our
      results suggest that the physiological properties of the histamine receptors are
      basically conserved among insects, but that the response to GABA differs between
      butterflies and flies, implying variation in early visual processing among
      species.

PMID- 30190316
TI  - Effects of both cold and heat stress on the liver of the giant spiny frog
      (Quasipaa spinosa): stress response and histological changes.
AB  - Ambient temperature-associated stress can affect normal physiological functions
      in ectotherms. To assess the effects of cold or heat stress on amphibians, giant
      spiny frogs (Quasipaa spinosa) were acclimated at 22 degrees C followed by
      exposure to 5 degrees C or 30 degrees C for 0, 3, 6, 12, 24 and 48 h,
      respectively. Histological alterations, apoptotic index, generation of
      mitochondrial reactive oxygen species (ROS), antioxidant activity indices and
      stress-response gene expression in frog livers were subsequently determined.
      Results showed that many fat droplets appeared after 12 h of heat stress and the
      percentage of melanomacrophage centres significantly changed after 48 h at both
      stress conditions. Furthermore, the mitochondrial ROS levels were elevated in a
      time-dependent manner up to 6 h and 12 h in the cold and heat stress groups,
      respectively. The activities of superoxide dismutase, glutathione peroxidase and
      catalase were successively increased with increasing periods of cold or heat
      exposure, and their gene expression levels showed similar changes in both stress
      conditions. Most tested heat shock protein (HSP) genes were sensitive to
      temperature exposure, and the expression profiles of most apoptosis-related genes
      was significantly upregulated at 3 and 48 h under cold and heat stress,
      respectively. Apoptotic index at 48 h under cold stress was significantly higher
      than that under heat stress. Notably, lipid droplets, HSP30, HSP70 and HSP110
      might be suitable bioindicators of heat stress. The results of these alterations
      at physiological, biochemical and molecular levels might contribute to a better
      understanding of the stress response of Q. spinosa, and perhaps amphibians more
      generally, under thermal stress.

PMID- 30190312
TI  - Toward an understanding of the structural basis of allostery in muscarinic
      acetylcholine receptors.
AB  - Recent breakthroughs and developments in structural biology have led to a spate
      of crystal structures for G protein-coupled receptors (GPCRs). This is the case
      for the muscarinic acetylcholine receptors (mAChRs) where inactive-state
      structures for four of the five subtypes and two active-state structures for one
      subtype are available. These mAChR crystal structures have provided new insights
      into receptor mechanisms, dynamics, and allosteric modulation. This is highly
      relevant to the mAChRs given that these receptors are an exemplar model system
      for the study of GPCR allostery. Allosteric mechanisms of the mAChRs are
      predominantly consistent with a two-state model, albeit with some notable recent
      exceptions. Herein, we discuss the mechanisms for positive and negative
      allosteric modulation at the mAChRs and compare and contrast these to evidence
      offered by pharmacological, biochemical, and computational approaches. This
      analysis provides insight into the fundamental pharmacological properties
      exhibited by GPCR allosteric modulators, such as enhanced subtype selectivity,
      probe dependence, and biased modulation while highlighting the current challenges
      that remain. Though complex, enhanced molecular understanding of allosteric
      mechanisms will have considerable influence on our understanding of GPCR
      activation and signaling and development of therapeutic interventions.

PMID- 30190318
TI  - Aerobic capacities and swimming performance of polar cod (Boreogadus saida) under
      ocean acidification and warming conditions.
AB  - Polar cod (Boreogadus saida) is an important prey species in the Arctic
      ecosystem, yet its habitat is changing rapidly: climate change, through rising
      seawater temperatures and CO2 concentrations, is projected to be most pronounced
      in Arctic waters. This study aimed to investigate the influence of ocean
      acidification and warming on maximum performance parameters of B. saida as
      indicators for the species' acclimation capacities under environmental conditions
      projected for the end of this century. After 4 months at four acclimation
      temperatures (0, 3, 6, 8 degrees C) each combined with two P CO2  levels (390 and
      1170 uatm), aerobic capacities and swimming performance of B. saida were recorded
      following a U crit protocol. At both CO2 levels, standard metabolic rate (SMR)
      was elevated at the highest acclimation temperature indicating thermal
      limitations. Maximum metabolic rate (MMR) increased continuously with
      temperature, suggesting an optimum temperature for aerobic scope for exercise
      (ASex) at 6 degrees C. Aerobic swimming performance (U gait) increased with
      acclimation temperature irrespective of CO2 levels, while critical swimming speed
      (U crit) did not reveal any clear trend with temperature. Hypercapnia evoked an
      increase in MMR (and thereby ASex). However, swimming performance (both U gait
      and U crit) was impaired under elevated near-future P CO2  conditions, indicating
      reduced efficiencies of oxygen turnover. The contribution of anaerobic metabolism
      to swimming performance was very low overall, and further reduced under
      hypercapnia. Our results revealed high sensitivities of maximum performance
      parameters (MMR, U gait, U crit) of B. saida to ocean acidification. Impaired
      swimming capacity under ocean acidification may reflect reduced future
      competitive strength of B. saida.

PMID- 30190319
TI  - The yellow specialist: dronefly Eristalis tenax prefers different yellow colours
      for landing and proboscis extension.
AB  - Droneflies, imagoes of the hoverfly Eristalis tenax, are known to possess a
      preference for yellow flowers, i.e. they prefer to visit yellow flowers and
      prefer to extend the proboscis to yellow colours. In this study we disentangle
      these colour preferences by investigating the landing reaction and proboscis
      reflex with particular reference to intensity, spectral purity and dominant
      wavelength of colour stimuli and their UV reflection properties. In multiple
      choice tests, naive and non-trained flies prefer to land on yellow colours
      independent of their UV reflection characteristics, but also accept blue, white
      and pink colours if they absorb UV and are of sufficient brightness. Flies
      trained to land on colours other than yellow still prefer yellow colours to some
      extent. Moreover, the flies prefer bright over dark yellow colours even if
      trained to dark yellow ones. The flies refuse to land on dark colours of all
      hues. Naive flies exhibit the proboscis reflex only to pure yellow pollen. These
      experiments show for the first time that landing in droneflies is triggered by a
      yellow colour independent of its UV reflection properties, but proboscis
      extension is triggered by yellow colours strongly absorbing blue and UV. The
      ability to discriminate colours is better than predicted by the categorical
      colour vision model. The colour preferences in E. tenax represent a fine-tuned
      ability to visit yellow flowers displaying a UV bull's-eye pattern.

PMID- 30190320
TI  - Dietary antioxidants, but not courtship effort, affect oxidative balance in the
      testes and muscles of crickets.
AB  - Recent interest has focused on the role of reactive oxygen species (ROS) as
      universal constraints in life-history evolution. Empirical studies have examined
      the oxidative costs of reproduction for females, with little work conducted on
      males. The male germline is thought to be particularly susceptible to oxidative
      damage because the testes, and the sperm themselves, can be prolific producers of
      ROS. We tested the hypothesis that protection of the male germline from oxidative
      damage represents a cost of reproduction for males. We fed male crickets,
      Teleogryllus oceanicus, with one of two experimental diets in which we
      manipulated the availability of dietary antioxidants, and we induced variation in
      their expenditure on courtship effort by manipulating access to females. We
      measured the total antioxidant capacity, levels of ROS production and the amount
      of oxidative damage to proteins in both testis and thoracic muscle tissues.
      Dietary antioxidants contributed to positive oxidative balance in both tissue
      types. Although the testes had greater antioxidant defences than muscle tissue,
      they also produced considerably higher levels of ROS and sustained higher levels
      of oxidative damage. Courtship effort had no impact on any measure of oxidative
      balance. Our data confirm that the male germline is especially susceptible to
      oxidative stress and that dietary antioxidants can alleviate this oxidative cost
      of reproduction.

PMID- 30190321
TI  - Measurable residual disease monitoring by NGS before allogeneic hematopoietic
      cell transplantation in AML.
AB  - Molecular measurable residual disease (MRD) assessment is not established in
      approximately 60% of acute myeloid leukemia (AML) patients because of the lack of
      suitable markers for quantitative real-time polymerase chain reaction. To
      overcome this limitation, we established an error-corrected next-generation
      sequencing (NGS) MRD approach that can be applied to any somatic gene mutation.
      The clinical significance of this approach was evaluated in 116 AML patients
      undergoing allogeneic hematopoietic cell transplantation (alloHCT) in complete
      morphologic remission (CR). Targeted resequencing at the time of diagnosis
      identified a suitable mutation in 93% of the patients, covering 24 different
      genes. MRD was measured in CR samples from peripheral blood or bone marrow before
      alloHCT and identified 12 patients with persistence of an ancestral clone
      (variant allele frequency [VAF] >5%). The remaining 96 patients formed the final
      cohort of which 45% were MRD+ (median VAF, 0.33%; range, 0.016%-4.91%). In
      competing risk analysis, cumulative incidence of relapse (CIR) was higher in MRD+
      than in MRD- patients (hazard ratio [HR], 5.58; P < .001; 5-year CIR, 66% vs
      17%), whereas nonrelapse mortality was not significantly different (HR, 0.60; P =
      .47). In multivariate analysis, MRD positivity was an independent negative
      predictor of CIR (HR, 5.68; P < .001), in addition to FLT3-ITD and NPM1 mutation
      status at the time of diagnosis, and of overall survival (HR, 3.0; P = .004), in
      addition to conditioning regimen and TP53 and KRAS mutation status. In
      conclusion, NGS-based MRD is widely applicable to AML patients, is highly
      predictive of relapse and survival, and may help refine transplantation and
      posttransplantation management in AML patients.

PMID- 30190323
TI  - Natural killer cells induce distinct modes of cancer cell death: Discrimination,
      quantification, and modulation of apoptosis, necrosis, and mixed forms.
AB  - Immune therapy of cancer is among the most promising recent advances in medicine.
      Whether the immune system can keep cancer in check depends on, among other
      factors, the efficiency of immune cells to recognize and eliminate cancer cells.
      We describe a time-resolved single-cell assay that reports the quality, quantity,
      and kinetics of target cell death induced by single primary human natural killer
      (NK) cells. The assay reveals that single NK cells induce cancer cell death by
      apoptosis and necrosis but also by mixed forms. Inhibition of either one of the
      two major cytotoxic pathways, perforin/granzyme release or FasL/FasR interaction,
      unmasked the parallel activity of the other one. Ca2+ influx through Orai
      channels is important for tuning killer cell function. We found that the
      apoptosis/necrosis ratio of cancer cell death by NK cells is controlled by the
      magnitude of Ca2+ entry and furthermore by the relative concentrations of
      perforin and granzyme B. The possibility to change the apoptosis/necrosis ratio
      employed by NK cells offers an intriguing possibility to modulate the
      immunogenicity of the tumor microenvironment.

PMID- 30190324
TI  - A motif in HSP90 and P23 that links molecular chaperones to efficient estrogen
      receptor alpha methylation by the lysine methyltransferase SMYD2.
AB  - Heat shock protein 90 (HSP90) is a molecular chaperone that supervises folding of
      cellular signaling proteins such as steroid receptors and many protein kinases.
      HSP90 relies on ATP hydrolysis for powering a conformational circuit that helps
      fold the client protein. To that end, HSP90 binds to co-chaperone proteins that
      regulate ATP hydrolysis rate or interaction with client proteins. Co-chaperones
      such as P23, cell division cycle 37 (CDC37), or activator of HSP90 ATPase
      activity 1 (AHA1) interact with the N-terminal or middle domain of HSP90, whereas
      others, such as HSP70/HSP90-organizing protein (HOP), use tetratricopeptide
      repeat (TPR) domains to bind the EEVD motif at the very C-terminal end of HSP90.
      Recently, the lysine methyltransferase SET and MYND domain-containing 2 (SMYD2)
      has been proposed as an HSP90-binding partner, and interaction analyses indicate
      that SMYD2 binding to HSP90 is independent of the EEVD motif. Using the amplified
      luminescence proximity homogeneous assay (Alpha) technique, I identified a new
      (M/I/L/V)PXL motif at the C termini of HSP90 and P23 that mediates an interaction
      with SMYD2, and synthetic peptides harboring this motif dissociated this complex.
      Of note, the HSP90- and P23-dependent client estrogen receptor alpha (ERalpha),
      was a major methylation target of SMYD2. In a reconstituted system in bacteria, I
      analyzed HSP90/P23-associated, SMYD2-mediated ERalpha methylation and found that
      when SMYD2 binds to the molecular chaperones, it considerably increases
      methylation of Lys-266 in ERalpha. Because methylation represses ERalpha
      activity, the observed complex formation between SMYD2 and HSP90/P23 may
      contribute to ERalpha regulation.

PMID- 30190322
TI  - CRISPR-delivery particles targeting nuclear receptor-interacting protein 1
      (Nrip1) in adipose cells to enhance energy expenditure.
AB  - RNA-guided, engineered nucleases derived from the prokaryotic adaptive immune
      system CRISPR-Cas represent a powerful platform for gene deletion and editing.
      When used as a therapeutic approach, direct delivery of Cas9 protein and single
      guide RNA (sgRNA) could circumvent the safety issues associated with plasmid
      delivery and therefore represents an attractive tool for precision genome
      engineering. Gene deletion or editing in adipose tissue to enhance its energy
      expenditure, fatty acid oxidation, and secretion of bioactive factors through a
      "browning" process presents a potential therapeutic strategy to alleviate
      metabolic disease. Here, we developed "CRISPR-delivery particles," denoted CriPs,
      composed of nano-size complexes of Cas9 protein and sgRNA that are coated with an
      amphipathic peptide called Endo-Porter that mediates entry into cells. Efficient
      CRISPR-Cas9-mediated gene deletion of ectopically expressed GFP by CriPs was
      achieved in multiple cell types, including a macrophage cell line, primary
      macrophages, and primary pre-adipocytes. Significant GFP loss was also observed
      in peritoneal exudate cells with minimum systemic toxicity in GFP-expressing mice
      following intraperitoneal injection of CriPs containing Gfp-targeting sgRNA.
      Furthermore, disruption of a nuclear co-repressor of catabolism, the Nrip1 gene,
      in white adipocytes by CriPs enhanced adipocyte browning with a marked increase
      of uncoupling protein 1 (UCP1) expression. Of note, the CriP-mediated Nrip1
      deletion did not produce detectable off-target effects. We conclude that CriPs
      offer an effective Cas9 and sgRNA delivery system for ablating targeted gene
      products in cultured cells and in vivo, providing a potential therapeutic
      strategy for metabolic disease.

PMID- 30190326
TI  - Long-chain acyl-CoA synthetase 1 interacts with key proteins that activate and
      direct fatty acids into niche hepatic pathways.
AB  - Fatty acid channeling into oxidation or storage modes depends on physiological
      conditions and hormonal signaling. However, the directionality of this channeling
      may also depend on the association of each of the five acyl-CoA synthetase
      isoforms with specific protein partners. Long-chain acyl-CoA synthetases (ACSLs)
      catalyze the conversion of long-chain fatty acids to fatty acyl-CoAs, which are
      then either oxidized or used in esterification reactions. In highly oxidative
      tissues, ACSL1 is located on the outer mitochondrial membrane (OMM) and directs
      fatty acids into mitochondria for beta-oxidation. In the liver, however, about
      50% of ACSL1 is located on the endoplasmic reticulum (ER) where its metabolic
      function is unclear. Because hepatic fatty acid partitioning is likely to require
      the interaction of ACSL1 with other specific proteins, we used an unbiased
      protein interaction technique, BioID, to discover ACSL1-binding partners in
      hepatocytes. We targeted ACSL1 either to the ER or to the OMM of Hepa 1-6 cells
      as a fusion protein with the Escherichia coli biotin ligase, BirA*. Proteomic
      analysis identified 98 proteins that specifically interacted with ACSL1 at the
      ER, 55 at the OMM, and 43 common to both subcellular locations. We found subsets
      of peroxisomal and lipid droplet proteins, tethering proteins, and vesicle
      proteins, uncovering a dynamic role for ACSL1 in organelle and lipid droplet
      interactions. Proteins involved in lipid metabolism were also identified,
      including acyl-CoA-binding proteins and ceramide synthase isoforms 2 and 5. Our
      results provide fundamental and detailed insights into protein interaction
      networks that control fatty acid metabolism.

PMID- 30190327
TI  - Plasma membrane profiling during enterohemorrhagic E. coli infection reveals that
      the metalloprotease StcE cleaves CD55 from host epithelial surfaces.
AB  - Enterohemorrhagic Escherichia coli (EHEC) is one of several E. coli pathotypes
      that infect the intestinal tract and cause disease. Formation of the
      characteristic attaching and effacing lesion on the surface of infected cells
      causes significant remodeling of the host cell surface; however, limited
      information is available about changes at the protein level. Here we employed
      plasma membrane profiling, a quantitative cell-surface proteomics technique, to
      identify host proteins whose cell-surface levels are altered during infection.
      Using this method, we quantified more than 1100 proteins, 280 of which showed
      altered cell-surface levels after exposure to EHEC. 22 host proteins were
      significantly reduced on the surface of infected epithelial cells. These included
      both known and unknown targets of EHEC infection. The complement decay
      accelerating factor cluster of differentiation 55 (CD55) exhibited the greatest
      reduction in cell-surface levels during infection. We showed by flow cytometry
      and Western blot analysis that CD55 is cleaved from the cell surface by the EHEC
      specific protease StcE and found that StcE-mediated CD55 cleavage results in
      increased neutrophil adhesion to the apical surface of intestinal epithelial
      cells. This suggests that StcE alters host epithelial surfaces to depress
      neutrophil transepithelial migration during infection. This work is the first
      report of the global manipulation of the epithelial cell surface by a bacterial
      pathogen and illustrates the power of quantitative cell-surface proteomics in
      uncovering critical aspects of bacterial infection biology.

PMID- 30190325
TI  - H2O2 oxidation of cysteine residues in c-Jun N-terminal kinase 2 (JNK2)
      contributes to redox regulation in human articular chondrocytes.
AB  - Reactive oxygen species (ROS), in particular H2O2, regulate intracellular
      signaling through reversible oxidation of reactive protein thiols present in a
      number of kinases and phosphatases. H2O2 has been shown to regulate mitogen
      activated protein kinase (MAPK) signaling depending on the cellular context. We
      report here that in human articular chondrocytes, the MAPK family member c-Jun N
      terminal kinase 2 (JNK2) is activated by fibronectin fragments and low
      physiological levels of H2O2 and inhibited by oxidation due to elevated levels of
      H2O2 The kinase activity of affinity-purified, phosphorylated JNK2 from cultured
      chondrocytes was reversibly inhibited by 5-20 MUm H2O2 Using dimedone-based
      chemical probes that react specifically with sulfenylated cysteines (RSOH), we
      identified Cys-222 in JNK2, a residue not conserved in JNK1 or JNK3, as a redox
      reactive site. MS analysis of human recombinant JNK2 also detected further
      oxidation at Cys-222 and other cysteines to sulfinic (RSO2H) or sulfonic (RSO3H)
      acid. H2O2 treatment of JNK2 resulted in detectable levels of peptides containing
      intramolecular disulfides between Cys-222 and either Cys-213 or Cys-177, without
      evidence of dimer formation. Substitution of Cys-222 to alanine rendered JNK2
      insensitive to H2O2 inhibition, unlike C177A and C213A variants. Two other JNK2
      variants, C116A and C163A, were also resistant to oxidative inhibition.
      Cumulatively, these findings indicate differential regulation of JNK2 signaling
      dependent on H2O2 levels and point to key cysteine residues regulating JNK2
      activity. As levels of intracellular H2O2 rise, a switch occurs from activation
      to inhibition of JNK2 activity, linking JNK2 regulation to the redox status of
      the cell.

PMID- 30190329
TI  - Lipids modulate the insertion and folding of the nascent chains of alpha helical
      membrane proteins.
AB  - Membrane proteins must be inserted into a membrane and folded into their correct
      structure to function correctly. This insertion occurs during translation and
      synthesis by the ribosome for most alpha-helical membrane proteins. Precisely how
      this co-translational insertion and folding occurs, and the role played by the
      surrounding lipids, is still not understood. Most of the work on the influence of
      the lipid environment on folding and insertion has focussed on denatured, fully
      translated proteins, and thus does not replicate folding during unidirectional
      elongation of nascent chains that occurs in the cell. This review aims to
      highlight recent advances in elucidating lipid composition and bilayer properties
      optimal for insertion and folding of nascent chains in the membrane and in the
      assembly of oligomeric proteins.

PMID- 30190328
TI  - Do nitric oxide, carbon monoxide and hydrogen sulfide really qualify as
      'gasotransmitters' in bacteria?
AB  - A gasotransmitter is defined as a small, generally reactive, gaseous molecule
      that, in solution, is generated endogenously in an organism and exerts important
      signalling roles. It is noteworthy that these molecules are also toxic and
      antimicrobial. We ask: is this definition of a gasotransmitter appropriate in the
      cases of nitric oxide, carbon monoxide and hydrogen sulfide (H2S) in microbes?
      Recent advances show that, not only do bacteria synthesise each of these gases,
      but the molecules also have important signalling or messenger roles in addition
      to their toxic effects. However, strict application of the criteria proposed for
      a gasotransmitter leads us to conclude that the term 'small molecule signalling
      agent', as proposed by Fukuto and others, is preferable terminology.

PMID- 30190330
TI  - Dissecting the role of His domain protein tyrosine phosphatase/PTPN23 and ESCRTs
      in sorting activated epidermal growth factor receptor to the multivesicular body.
AB  - Sorting of activated epidermal growth factor receptor (EGFR) into intraluminal
      vesicles (ILVs) within the multivesicular body (MVB) is an essential step during
      the down-regulation of the receptor. The machinery that drives EGFR sorting
      attaches to the cytoplasmic face of the endosome and generates vesicles that bud
      into the endosome lumen, but somehow escapes encapsulation itself. This machinery
      is termed the ESCRT (endosomal sorting complexes required for transport) pathway,
      a series of multi-protein complexes and accessory factors first identified in
      yeast. Here, we review the yeast ESCRT pathway and describe the corresponding
      components in mammalian cells that sort EGFR. One of these is His domain protein
      tyrosine phosphatase (HD-PTP/PTPN23), and we review the interactions involving HD
      PTP and ESCRTs. Finally, we describe a working model for how this ESCRT pathway
      might overcome the intrinsic topographical problem of EGFR sorting to the MVB
      lumen.

PMID- 30190332
TI  - The discovery of hydrogen bonds in DNA and a re-evaluation of the 1948 Creeth two
      chain model for its structure.
AB  - We recall the experimental approaches involved in the discovery of hydrogen bonds
      in deoxyribonucleic acid (DNA) made 70 years ago by a team of scientists at
      University College Nottingham led by J.M. Gulland, and in relation to previous
      studies. This discovery proved an important step in the elucidation of the
      correct structure for DNA made by J.D. Watson and F.H.C. Crick, as acknowledged
      in 'The Double Helix'. At that time of the discovery, however, it was impossible
      to delineate between inter- and intra-chain hydrogen bonds. We also consider in
      the light of more recent hydrodynamic theory a tentative model for DNA proposed
      by Gulland's and D.O. Jordan's PhD student J.M. Creeth in his PhD thesis of 1948,
      with the correct prediction of two chains with a sugar-phosphate backbone on the
      exterior and hydrogen-bonded bases between the nucleotide bases of opposite
      chains in the interior. Our analysis shows that his incorporation of alternating
      breaks in the two-chain structure was not necessary to explain the viscosity data
      on scission of hydrogen bonds after titrating to high or low pH. Although
      Creeth's model is a depiction of DNA structure alone, he could not know whether
      the hydrogen bonding was intermolecular, although this was subsequently proved
      correct by others. The mechanisms by which replicative processes occurred were of
      course unknown at that time, and so, he could not have realised how closely his
      tentative model resembled steps in some viral replicative mechanisms involving
      the molecule of life that he was working on.

PMID- 30190331
TI  - Recent advances in threshold-dependent gene drives for mosquitoes.
AB  - Mosquito-borne diseases, such as malaria, dengue and chikungunya, cause morbidity
      and mortality around the world. Recent advances in gene drives have produced
      control methods that could theoretically modify all populations of a disease
      vector, from a single release, making whole species less able to transmit
      pathogens. This ability has caused both excitement, at the prospect of global
      eradication of mosquito-borne diseases, and concern around safeguards. Drive
      mechanisms that require individuals to be released at high frequency before genes
      will spread can therefore be desirable as they are potentially localised and
      reversible. These include underdominance-based strategies and use of the
      reproductive parasite Wolbachia Here, we review recent advances in practical
      applications and mathematical analyses of these threshold-dependent gene drives
      with a focus on implementation in Aedes aegypti, highlighting their mechanisms
      and the role of fitness costs on introduction frequencies. Drawing on the
      parallels between these systems offers useful insights into practical, controlled
      application of localised drives, and allows us to assess the requirements needed
      for gene drive reversal.

PMID- 30190333
TI  - Stress signaling in breast cancer cells induces matrix components that promote
      chemoresistant metastasis.
AB  - Metastatic progression remains a major burden for cancer patients and is
      associated with eventual resistance to prevailing therapies such as chemotherapy.
      Here, we reveal how chemotherapy induces an extracellular matrix (ECM), wound
      healing, and stem cell network in cancer cells via the c-Jun N-terminal kinase
      (JNK) pathway, leading to reduced therapeutic efficacy. We find that elevated JNK
      activity in cancer cells is linked to poor clinical outcome in breast cancer
      patients and is critical for tumor initiation and metastasis in xenograft mouse
      models of breast cancer. We show that JNK signaling enhances expression of the
      ECM and stem cell niche components osteopontin, also called secreted
      phosphoprotein 1 (SPP1), and tenascin C (TNC), that promote lung metastasis. We
      demonstrate that both SPP1 and TNC are direct targets of the c-Jun transcription
      factor. Exposure to multiple chemotherapies further exploits this JNK-mediated
      axis to confer treatment resistance. Importantly, JNK inhibition or disruption of
      SPP1 or TNC expression sensitizes experimental mammary tumors and metastases to
      chemotherapy, thus providing insights to consider for future treatment strategies
      against metastatic breast cancer.

PMID- 30190336
TI  - Celebrating 35 Years of the AJNR: September 1983 edition.

PMID- 30190334
TI  - Selective depletion of metastatic stem cells as therapy for human colorectal
      cancer.
AB  - Selective elimination of metastatic stem cells (MetSCs) promises to block
      metastatic dissemination. Colorectal cancer (CRC) cells overexpressing CXCR4
      display trafficking functions and metastasis-initiating capacity. We assessed the
      antimetastatic activity of a nanoconjugate (T22-GFP-H6-FdU) that selectively
      delivers Floxuridine to CXCR4+ cells. In contrast to free oligo-FdU, intravenous
      T22-GFP-H6-FdU selectively accumulates and internalizes in CXCR4+ cancer cells,
      triggering DNA damage and apoptosis, which leads to their selective elimination
      and to reduced tumor re-initiation capacity. Repeated T22-GFP-H6-FdU
      administration in cell line and patient-derived CRC models blocks intravasation
      and completely prevents metastases development in 38-83% of mice, while showing
      CXCR4 expression-dependent and site-dependent reduction in foci number and size
      in liver, peritoneal, or lung metastases in the rest of mice, compared to free
      oligo-FdU. T22-GFP-H6-FdU induces also higher regression of established
      metastases than free oligo-FdU, with negligible distribution or toxicity in
      normal tissues. This targeted drug delivery approach yields potent antimetastatic
      effect, through selective depletion of metastatic CXCR4+ cancer cells, and
      validates metastatic stem cells (MetSCs) as targets for clinical therapy.

PMID- 30190338
TI  - Inhibition of Intestinal Epithelial Wound Healing through Protease-Activated
      Receptor-2 Activation in Caco2 Cells.
AB  - The mechanisms of epithelial wound healing are not completely understood,
      especially in the context of proteases and their receptors. It was recently shown
      that activation of protease-activated receptor-2 (PAR2) on intestinal epithelial
      cells induced the expression of cyclooxygenase-2 (COX-2), which has protective
      functions in the gastrointestinal tract. It was hypothesized that PAR2-induced
      COX-2 could enhance wound healing in intestinal epithelial cells. Caco2 cells
      were used to model epithelial wound healing of circular wounds. Cellular
      proliferation was studied with a 5-ethynyl-2'-deoxyuridine assay, and migration
      was studied during wound healing in the absence of proliferation.
      Immunofluorescence was used to visualize E-cadherin and F-actin, and the cellular
      transcription profile during wound healing and PAR2 activation was explored with
      RNA sequencing. PAR2 activation inhibited Caco2 wound healing by reducing cell
      migration, independently of COX-2 activity. Interestingly, even though migration
      was reduced, proliferation was increased. When the actin dynamics and cell-cell
      junctions were investigated, PAR2 activation was found to induce actin cabling
      and prevent the internalization of E-cadherin. To further investigate the effect
      of PAR2 on transcriptionally dependent wound healing, RNA sequencing was
      performed. This analysis revealed that PAR2 activation, in the absence of
      wounding, induced a similar transcriptional profile compared with wounding alone.
      These findings represent a novel effect of PAR2 activation on the mechanisms of
      epithelial cell wound healing that could influence the resolution of intestinal
      inflammation.

PMID- 30190335
TI  - Mutations in TIMM50 compromise cell survival in OxPhos-dependent metabolic
      conditions.
AB  - TIMM50 is an essential component of the TIM23 complex, the mitochondrial inner
      membrane machinery that imports cytosolic proteins containing a mitochondrial
      targeting presequence into the mitochondrial inner compartment. Whole exome
      sequencing (WES) identified compound heterozygous pathogenic mutations in TIMM50
      in an infant patient with rapidly progressive, severe encephalopathy. Patient
      fibroblasts presented low levels of TIMM50 and other components of the TIM23
      complex, lower mitochondrial membrane potential, and impaired TIM23-dependent
      protein import. As a consequence, steady-state levels of several components of
      mitochondrial respiratory chain were decreased, resulting in decreased
      respiration and increased ROS production. Growth of patient fibroblasts in
      galactose shifted energy production metabolism toward oxidative phosphorylation
      (OxPhos), producing an apparent improvement in most of the above features but
      also increased apoptosis. Complementation of patient fibroblasts with TIMM50
      improved or restored these features to control levels. Moreover, RNASEH1 and ISCU
      mutant fibroblasts only shared a few of these features with TIMM50 mutant
      fibroblasts. Our results indicate that mutations in TIMM50 cause multiple
      mitochondrial bioenergetic dysfunction and that functional TIMM50 is essential
      for cell survival in OxPhos-dependent conditions.

PMID- 30190337
TI  - Pharmacology, Pharmacokinetics, and Tissue Disposition of Zwitterionic
      Hydroxyiminoacetamido Alkylamines as Reactivating Antidotes for Organophosphate
      Exposure.
AB  - In the development of antidotal therapy for treatment of organophosphate exposure
      from pesticides used in agriculture and nerve agents insidiously employed in
      terrorism, the alkylpyridinium aldoximes have received primary attention since
      their early development by I. B. Wilson in the 1950s. Yet these agents, by virtue
      of their quaternary structure, are limited in rates of crossing the blood-brain
      barrier, and they require administration parenterally to achieve full
      distribution in the body. Oximes lacking cationic charges or presenting a
      tertiary amine have been considered as alternatives. Herein, we examine the
      pharmacokinetic properties of a lead ionizable, zwitterionic
      hydroxyiminoacetamido alkylamine in mice to develop a framework for studying
      these agents in vivo and generate sufficient data for their consideration as
      appropriate antidotes for humans. Consequently, in vitro and in vivo efficacies
      of immediate structural congeners were explored as leads or backups for animal
      studies. We compared oral and parenteral dosing, and we developed an
      intramuscular loading and oral maintenance dosing scheme in mice. Steady-state
      plasma and brain levels of the antidote were achieved with sequential
      administrations out to 10 hours, with brain levels exceeding plasma levels
      shortly after administration. Moreover, the zwitterionic oxime showed substantial
      protection after gavage, whereas the classic methylpyridinium aldoxime (2
      pyridinealdoxime methiodide) was without evident protection. Although further
      studies in other animal species are necessary, ionizing zwitterionic aldoximes
      present viable alternatives to existing antidotes for prophylaxis and treatment
      of large numbers of individuals in terrorist-led events with nerve agent
      organophosphates, such as sarin, and in organophosphate pesticide exposure.

PMID- 30190340
TI  - Rise in long term consultant vacancies in Scotland is "deeply troubling," says
      BMA.

PMID- 30190341
TI  - Efficacy of venetoclax monotherapy in patients with relapsed, refractory mantle
      cell lymphoma post BTK inhibitor therapy.

PMID- 30190342
TI  - Prognostic implications of additional genomic lesions in adult Ph+ acute
      lymphoblastic leukemia.
AB  - To shed light into the molecular basis of Ph+ acute lymphoblastic leukemia and to
      investigate the prognostic role of additional genomic lesions, we analyzed copy
      number aberrations using the Cytoscan HD Array in 116 newly diagnosed adult Ph+
      acute lymphoblastic leukemia patients enrolled in four different GIMEMA
      protocols, all based on a chemotherapy-free induction strategy. This analysis
      showed that Ph+ acute lymphoblastic leukemia patients carry 7.8 lesions/case on
      average, with deletions outnumbering gains (88% vs 12%). The most common
      deletions were those targeting IKZF1, PAX5 and CDKN2A/B detected in 84%, 36% and
      32% of cases, respectively. Patients carrying simultaneous deletions of IKZF1
      plus CDKN2A/B and/or PAX5 had a significantly worse disease-free survival (24.9%
      vs 43.3%, p=0.026). The only IKZF1 isoform impacting on prognosis was the
      dominant negative (p=0.003). Copy number aberrations analysis showed that 18% of
      patients harbored MEF2C deletions, which were of two types, differing in size:
      the longer deletions were associated with the achievement of a complete molecular
      remission (p=0.05) and had a favorable impact on disease-free survival (64.3% vs
      32.1% at 36 months, p=0.031). These findings retain statistical significance also
      in multivariate analysis (p=0.057). KRAS deletions, detected in 6% of cases, were
      associated with the achievement of a complete molecular remission (p=0.009).
      These results indicate that in adult Ph+ acute lymphoblastic leukemia a detailed
      evaluation of additional deletions - including CDKN2A/B, PAX5, IKZF1, MEF2C and
      KRAS - has prognostic implications and should be incorporated in the design of
      always more personalized treatment strategies.

PMID- 30190339
TI  - Molecular Neuroprotection Induced by Zinc-Dependent Expression of Hepatitis C
      Derived Protein NS5A Targeting Kv2.1 Potassium Channels.
AB  - We present the design of an innovative molecular neuroprotective strategy and
      provide proof-of-concept for its implementation, relying on the injury-mediated
      activation of an ectopic gene construct. As oxidative injury leads to the
      intracellular liberation of zinc, we hypothesize that tapping onto the zinc
      activated metal regulatory element (MRE) transcription factor 1 system to drive
      expression of the Kv2.1-targeted hepatitis C protein NS5A (hepatitis C
      nonstructural protein 5A) will provide neuroprotection by preventing cell death
      enabling cellular potassium loss in rat cortical neurons in vitro. Indeed, using
      biochemical and morphologic assays, we demonstrate rapid expression of MRE-driven
      products in neurons. Further, we report that MRE-driven NS5A expression, induced
      by a slowly evolving excitotoxic stimulus, functionally blocks injurious,
      enhanced Kv2.1 potassium whole-cell currents and improves neuronal viability. We
      suggest this form of "on-demand" neuroprotection could provide the basis for a
      tenable therapeutic strategy to prevent neuronal cell death in neurodegeneration.

PMID- 30190343
TI  - Rituximab with ABVD vs ABVD for advanced stage high-risk classical Hodgkin
      lymphoma: a randomized phase II study.

PMID- 30190345
TI  - Comprehensive genetic diagnosis of acute myeloid leukemia by next generation
      sequencing.
AB  - Differential induction therapy of all subtypes of Acute Myeloid Leukemia other
      than Acute Promyelocytic Leukemia is impeded by the long time required to
      complete complex and diverse cytogenetic and molecular genetic analyses for risk
      stratification or targeted treatment decisions. Here, we describe a reliable,
      rapid and sensitive diagnostic approach that combines karyotyping and mutational
      screening in a single integrated next generation sequencing assay. Numerical
      karyotyping was performed by low coverage whole genome sequencing followed by
      copy number variation analysis using a novel algorithm based on in silico
      generated reference karyotypes. Translocations and DNA variants were examined by
      targeted resequencing of fusion transcripts and mutational hotspot regions using
      commercially available kits and analysis pipelines. For the identification of
      FLT3 internal tandem duplications and KMT2A partial tandem duplications, we
      adapted previously described tools. In a validation cohort including 22 primary
      patient samples, 9/9 numerically normal karyotypes were classified correctly and
      30/31 (97%) Copy number variations reported by classical cytogenetics and FISH
      analysis were uncovered by our next generation sequencing-karyotyping approach.
      Predesigned fusion and mutation panels were validated exemplarily on leukemia
      cell lines and a subset of patient samples and identified all expected genomic
      alterations. Finally, blinded analysis of eight additional patient samples using
      our comprehensive assay accurately reproduced reference results. Therefore,
      calculated karyotyping by low coverage whole genome sequencing allows for fast
      and reliable detection of numerical chromosomal changes and, in combination with
      panel-based fusion- and mutation screening, will greatly facilitate
      implementation of subtype-specific induction therapies in Acute Myeloid Leukemia.

PMID- 30190346
TI  - Advice for Indian states to ban electronic nicotine delivery systems spark
      criticism.

PMID- 30190344
TI  - CD38 as a therapeutic target for adult acute myeloid leukemia and T-cell acute
      lymphoblastic leukemia.
AB  - "-".

PMID- 30190347
TI  - Blood Pressure Elevation and Risk of Moyamoya Syndrome in Patients With Trisomy
      21.
AB  - OBJECTIVES: Individuals with Down syndrome (DS) are at risk for the development
      of moyamoya syndrome (MMS); MMS is often recognized only after a resulting stroke
      has occurred. Our goal with this study was to determine if elevations in blood
      pressure (BP) precede acute presentation of MMS in individuals with DS. METHODS:
      A single-center, retrospective case-control study was performed. Thirty patients
      with MMS and DS and 116 patients with DS only were identified retrospectively.
      Three BP recordings were evaluated at set intervals (18-24 months, 12-18 months,
      and 6-12 months before diagnosis of MMS). These were then compared against
      control averages from patients with DS only. To assess changes over the time, we
      used general linear model repeated measures analysis of variance. To identify
      independent predictors of MMS and DS, we used a multivariable analysis using
      generalized estimating equations accounting for repeated measures of BP. RESULTS:
      BP in patients with MMS and DS rose significantly over the 24-month period
      preceding presentation (34th, 42nd, and 70th percentiles at the 18-24-month, 12
      18-month, and 6-12-month periods, respectively). BPs in the patients with both
      MMS and DS were significantly higher than in the DS-only controls in the 6 to 12
      (P < .001) and 12 to 18 months before presentation (P = .016). Higher Suzuki
      scores, bilateral disease, and posterior circulation involvement were also
      predictive of BP elevation before presentation. CONCLUSIONS: Elevations in BP may
      foreshadow presentation of MMS in individuals with DS. This simple, low-cost
      screening measure may lead to early identification of at-risk patients in the
      medical home and prevent irreversible neurologic injury.

PMID- 30190348
TI  - Eliciting Narratives to Inform Care for Infants With Trisomy 18.
AB  - : media-1vid110.1542/5804913218001PEDS-VA_2018-0321Video Abstract.

PMID- 30190349
TI  - Heme, whence come thy carbon building blocks?

PMID- 30190350
TI  - CART19 in Hodgkin lymphoma: are we driving the right model?

PMID- 30190351
TI  - A miRaculous new therapy in myeloma?

PMID- 30190352
TI  - ADAMTS-13 in traumatic brain injury?

PMID- 30190353
TI  - Spindle cell lesion in the bone marrow.

PMID- 30190354
TI  - Multiple subperiosteal bone resorption in adult T-cell leukemia/lymphoma.

PMID- 30190355
TI  - Building a Pool of Future Technologist Authors.

PMID- 30190356
TI  - Erratum.

PMID- 30190357
TI  - The Model Practice Act for Nuclear Medicine Technology.

PMID- 30190358
TI  - JRCNMT Report.

PMID- 30190359
TI  - Technologist News.

PMID- 30190360
TI  - Advancing the Profession with a Focus on Value and Quality.

PMID- 30190361
TI  - IAC Grants First CT Accreditation to a Mobile Stroke Unit.

PMID- 30190362
TI  - Death certificates should record antimicrobial resistance as cause of deaths,
      says CMO.

PMID- 30190363
TI  - Activation of Caenorhabditis elegans Levamisole-Sensitive and Mammalian Nicotinic
      Receptors by the Antiparasitic Bephenium.
AB  - Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels involved
      in neuromuscular transmission. In nematodes, muscle nAChRs are targets of
      antiparasitic drugs. Bephenium is an anthelmintic compound whose molecular action
      in the free-living nematode Caenorhabditis elegans, which is a model for
      anthelmintic drug discovery, is poorly known. We explored the effect of bephenium
      on C. elegans locomotion and applied single-channel recordings to identify its
      molecular target, mechanism of action, and selectivity between mammalian and C.
      elegans nAChRs. As in parasites, bephenium paralyzes C. elegans A mutant strain
      lacking the muscle levamisole-sensitive nAChR (L-AChR) shows full resistance to
      bephenium, indicating that this receptor is the target site. Bephenium activates
      L-AChR channels from larvae muscle cells in the micromolar range. Channel
      activity is similar to that elicited by levamisole, appearing mainly as isolated
      brief openings. Our analysis revealed that bephenium is an agonist of L-AChR and
      an open-channel blocker at higher concentrations. It also activates mammalian
      muscle nAChRs. Opening events are significantly briefer than those elicited by
      ACh and do not appear in activation episodes at a range of concentrations,
      indicating that it is a very weak agonist of mammalian nAChRs. Recordings in the
      presence of ACh showed that bephenium acts as a voltage-dependent channel blocker
      and a low-affinity agonist. Molecular docking into homology-modeled binding-site
      interfaces represent the binding mode of bephenium that explains its partial
      agonism. Given the great diversity of helminth nAChRs and the overlap of their
      pharmacological profiles, unraveling the basis of drug receptor-selectivity will
      be required for rational design of anthelmintic drugs.

PMID- 30190364
TI  - Quantitative assessment of outer retinal layers and ellipsoid zone mapping in
      hydroxychloroquine retinopathy.
AB  - BACKGROUND: To quantitatively assess outer retinal layers in eyes with
      hydroxychloroquine (HCQ) toxicity. METHODS: A retrospective case-control study
      was performed to identify eyes with HCQ retinopathy/toxicity at Cleveland Clinic.
      A clinical diagnosis of HCQ retinopathy was made based on clinical and imaging
      features including the presence of parafoveal ellipsoid zone (EZ) loss on
      spectral-domain optical coherence tomography (OCT) and visual field defects. All
      participants underwent macular cube scan using the Cirrus HD-OCT (Zeiss,
      Oberkochen, Germany). Quantitative assessment of outer nuclear layer (ONL)/Henle
      fibre layer complex (HFL) metrics and EZ mapping were performed with a novel
      software platform and compared with age-matched controls. HCQ toxicity group was
      divided into three subgroups based on the severity. RESULTS: There were 14 eyes
      from 14 patients in HCQ toxicity group (mean age 57.0+/-18.6 years), and 14 eyes
      from 14 subjects in age-matched control group (mean age 59.4+/-18.6 years).
      Multiple outer retinal parameters including ONL/HFL-EZ volume, parafoveal ONL/HFL
      EZ thickness and EZ-retinal pigment epithelium (RPE) volume were significantly
      reduced in all HCQ toxicity subgroups (early, moderate and advanced toxicity)
      compared with controls. Semiautomated layer segmentation tool produced en face
      representation of EZ-RPE mapping and allowed unique visualisation of EZ
      attenuation in eyes with HCQ toxicity. The longitudinal analysis of HCQ toxicity
      group demonstrated progressive decline in some outer retinal parameters.
      CONCLUSION: HCQ toxicity resulted in significant outer retinal layer volumetric
      thinning compared with controls. Quantitative assessment of outer retinal
      parameters and EZ mapping on SD-OCT may become a useful biomarker to identify and
      monitor HCQ toxicity.

PMID- 30190365
TI  - Distribution of preoperative and postoperative astigmatism in a large population
      of patients undergoing cataract surgery in the UK.
AB  - PURPOSE: To assess the prevalence and severity of preoperative and postoperative
      astigmatism in patients with cataract in the UK. SETTING: Data from 8 UK National
      Health Service ophthalmology clinics using MediSoft electronic medical records
      (EMRs). DESIGN: Retrospective cohort study. METHODS: Eyes from patients aged >=65
      years undergoing cataract surgery were analysed. For all eyes, preoperative
      (corneal) astigmatism was evaluated using the most recent keratometry measure
      within 2 years prior to surgery. For eyes receiving standard monofocal
      intraocular lens (IOLs), postoperative refractive astigmatism was evaluated using
      the most recent refraction measure within 2-12 months postsurgery. A power vector
      analysis compared changes in the astigmatic 2-dimensional vector (J0, J45) before
      and after surgery, for the subgroup of eyes with both preoperative and
      postoperative astigmatism measurements. Visual acuity was also assessed
      preoperatively and postoperatively. RESULTS: Eligible eyes included in the
      analysis were 110 468. Of these, 78% (n=85 650) had preoperative (corneal)
      astigmatism >=0.5 dioptres (D), 42% (n=46 003) >=1.0 D, 21% (n=22 899) >=1.5 D
      and 11% (n=11 651) >=2.0 D. After surgery, the refraction cylinder was available
      for 39 744 (36%) eyes receiving standard monofocal IOLs, of which 90% (n=35 907)
      had postoperative astigmatism >=0.5 D and 58% (n=22 886) >=1.0 D. Visual acuity
      tended to worsen postoperatively with increased astigmatism (rho=-0.44, P<0.01).
      CONCLUSIONS: There is a significant burden of preoperative astigmatism in the UK
      cataract population. The available refraction data indicate that this burden is
      not reduced after surgery with implantation of standard monofocal IOLs. Measures
      should be taken to improve visual outcomes of patients with astigmatic cataract
      by simultaneously correcting astigmatism during cataract surgery.

PMID- 30190367
TI  - One in seven operations cancelled on day of surgery, study finds.

PMID- 30190368
TI  - Tackling the youth mental health crisis across adolescence and young adulthood.

PMID- 30190366
TI  - Association between mitochondrial DNA damage and ocular blood flow in patients
      with glaucoma.
AB  - BACKGROUND/AIMS: We determined the relationship between tissue mean blur rate
      (MT) and mitochondrial dysfunction, represented by the mitochondrial/nuclear DNA
      (mtDNA/nDNA) ratio. We also investigated the usefulness of these biomarkers.
      METHODS: We assessed ocular blood flow in 123 eyes of 123 patients with open
      angle glaucoma (OAG) and 37 control eyes of 37 healthy subjects by measuring MT
      in the optic nerve head with laser speckle flowgraphy. We measured mtDNA and nDNA
      with PCR, calculated the mtDNA/nDNA ratio and compared this ratio with MT using
      Spearman's rank test. We used multiple regression analysis to further investigate
      the association between MT and glaucoma in the most severe group. RESULTS: The
      control and the patients with glaucoma had significant differences in the
      mtDNA/nDNA ratio, circumpapillary retinal nerve fibre layer thickness and MT.
      There was no significant relationship between the mtDNA/nDNA ratio and MT in
      patients with OAG overall or the female patients with OAG, but there was a
      significant relationship between the mtDNA/nDNA ratio and MT, temporal-MT and
      superior-MT in male patients with severe OAG (r=-0.46, p=0.03; r=-0.51, p=0.02;
      r=-0.61, p<0.01, respectively). Furthermore, we found that the mtDNA/nDNA ratio
      was an independent contributor to temporal-MT and superior-MT in these patients
      (p<0.01 and p=0.03, respectively). CONCLUSION: We found that there was a
      significant relationship between the mtDNA/nDNA ratio and MT in male patients
      with severe OAG, suggesting that the mtDNA/nDNA ratio may be a new biomarker in
      glaucoma and may help research on the vulnerability of these patients to
      mitochondrial dysfunction.

PMID- 30190369
TI  - A Phase II and Biomarker Study of Sorafenib Combined with Modified FOLFOX in
      Patients with Advanced Hepatocellular Carcinoma.
AB  - Purpose: Sorafenib is a standard first-line treatment for advanced hepatocellular
      carcinoma (HCC). The phase III SHARP trial showed a median time-to-progression
      (mTTP) of 5.5 months, overall response rate (ORR) of 2%, and median overall
      survival (mOS) of 10.7 months with sorafenib. FOLFOX4 has shown modest activity
      in advanced HCC. We evaluated the combination of sorafenib and modified (m)FOLFOX
      in a single-arm, multicenter phase II study.Experimental Design: The study
      included Child-Pugh A patients with advanced HCC and no prior systemic therapies.
      Patients received sorafenib 400 mg twice a day for 2 weeks, followed by
      concurrent mFOLFOX [5-fluorouracil (5-FU) 1,200 mg/m2/day for 46 hours,
      leucovorin 200 mg/m2, and oxaliplatin 85 mg/m2 biweekly]. The primary endpoint
      was mTTP with an alternative hypothesis of 7 months, and secondary endpoints
      included ORR, mOS, and circulating biomarkers.Results: The study enrolled 40
      patients: HCV/EtOH/HBV, 43%/28%/13%; Child-Pugh A5, 70%. Notable grade 3/4
      adverse events (AE) included AST/ALT elevation (28%/15%), diarrhea (13%),
      hyperbilirubinemia (10%), hand-foot syndrome (8%), and bleeding (8%). mTTP was
      7.7 months [95% confidence interval (CI): 4.4-8.9], ORR 18%, and mOS 15.1 months
      (7.9-16.9). Sorafenib + mFOLFOX increased plasma PlGF, VEGF-D, sVEGFR1, IL12p70,
      and CAIX and CD4+ and CD8+ effector T lymphocytes and decreased plasma sVEGFR2
      and s-c-KIT and regulatory T cells (Tregs). Shorter TTP was associated with high
      baseline sVEGFR1. Shorter TTP and OS were associated with increases in Tregs and
      CD56Dim natural killer (NK) cells after sorafenib alone and plasma sMET after
      combination treatment (all P < 0.05).Conclusions: Sorafenib + mFOLFOX met the
      prespecified endpoint with encouraging efficacy but moderate hepatotoxicity.
      Thus, this regimen may be effective in select patients with adequate liver
      reserve. Biomarker evaluations suggested a correlation between time-to
      progression (TTP) and angiogenic biomarkers and circulating Tregs. Clin Cancer
      Res; 1-10. (c)2018 AACR.

PMID- 30190370
TI  - Dietary Protein Restriction Reprograms Tumor-Associated Macrophages and Enhances
      Immunotherapy.
AB  - Purpose: Diet and healthy weight are established means of reducing cancer
      incidence and mortality. However, the impact of diet modifications on the tumor
      microenvironment and antitumor immunity is not well defined. Immunosuppressive
      tumor-associated macrophages (TAMs) are associated with poor clinical outcomes
      and are potentially modifiable through dietary interventions. We tested the
      hypothesis that dietary protein restriction modifies macrophage function toward
      antitumor phenotypes.Experimental Design: Macrophage functional status under
      different tissue culture conditions and in vivo was assessed by Western blot,
      immunofluorescence, qRT-PCR, and cytokine array analyses. Tumor growth in the
      context of protein or amino acid (AA) restriction and immunotherapy, namely, a
      survivin peptide-based vaccine or a PD-1 inhibitor, was examined in animal models
      of prostate (RP-B6Myc) and renal (RENCA) cell carcinoma. All tests were two
      sided.Results: Protein or AA-restricted macrophages exhibited enhanced
      tumoricidal, proinflammatory phenotypes, and in two syngeneic tumor models,
      protein or AA-restricted diets elicited reduced TAM infiltration, tumor growth,
      and increased response to immunotherapies. Further, we identified a distinct
      molecular mechanism by which AA-restriction reprograms macrophage function via a
      ROS/mTOR-centric cascade.Conclusions: Dietary protein restriction alters TAM
      activity and enhances the tumoricidal capacity of this critical innate immune
      cell type, providing the rationale for clinical testing of this supportive tool
      in patients receiving cancer immunotherapies. Clin Cancer Res; 1-13. (c)2018
      AACR.

PMID- 30190371
TI  - Clinical Pharmacology of Tisagenlecleucel in B-cell Acute Lymphoblastic Leukemia.
AB  - Background: Tisagenlecleucel is an anti-CD19 chimeric antigen receptor (CAR19) T
      cell therapy approved for the treatment of children and young adults with
      relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL).Methods: We
      evaluated the cellular kinetics of tisagenlecleucel, the effect of patient
      factors, humoral immunogenicity, and manufacturing attributes on its kinetics,
      and exposure-response analysis for efficacy, safety and pharmacodynamic endpoints
      in 79 patients across two studies in pediatric B-ALL (ELIANA and ENSIGN).Results:
      Using quantitative polymerase chain reaction to quantify levels of
      tisagenlecleucel transgene, responders (N = 62) had ~2-fold higher
      tisagenlecleucel expansion in peripheral blood than nonresponders (N = 8; 74% and
      104% higher geometric mean Cmax and AUC0-28d, respectively) with persistence
      measurable beyond 2 years in responding patients. Cmax increased with occurrence
      and severity of cytokine release syndrome (CRS). Tisagenlecleucel continued to
      expand and persist following tocilizumab, used to manage CRS. Patients with B
      cell recovery within 6 months had earlier loss of the transgene compared with
      patients with sustained clinical response. Clinical responses were seen across
      the entire dose range evaluated (patients <=50 kg: 0.2 to 5.0 * 106/kg; patients
      >50 kg: 0.1 to 2.5 * 108 CAR-positive viable T cells) with no relationship
      between dose and safety. Neither preexisting nor treatment-induced antimurine
      CAR19 antibodies affected the persistence or clinical response.Conclusion:
      Response to tisagenlecleucel was associated with increased expansion across a
      wide dose range. These results highlight the importance of cellular kinetics in
      understanding determinants of response to chimeric antigen receptor T-cell
      therapy. Clin Cancer Res; 1-10. (c)2018 AACR.

PMID- 30190372
TI  - Does TMB Impact the Effectiveness of TKIs in EGFR-Mutant NSCLC?
AB  - Patients with EGFR-mutant non-small cell lung cancer achieve variable benefit
      from targeted therapy, and biomarkers to predict degree of benefit are not in
      clinical use. EGFR-mutant cancers with high tumor mutational burden demonstrate
      poorer outcomes on EGFR-targeted therapy. Investigation into the mechanisms
      underlying this intriguing association is needed. Clin Cancer Res; 1-2. (c)2018
      AACR. See related article by Offin et al.

PMID- 30190373
TI  - Endoglycosidase S Enables a Highly Simplified Clinical Chemistry Procedure for
      Direct Assessment of Serum IgG Undergalactosylation in Chronic Inflammatory
      Disease.
AB  - Over the past 30 years, it has been firmly established that a wide spectrum of
      (autoimmune) diseases such as rheumatoid arthritis, Crohn's and lupus, but also
      other pathologies like alcoholic and non-alcoholic steatohepatitis (ASH and NASH)
      are driven by chronic inflammation and are hallmarked by a reduced level of serum
      IgG galactosylation. IgG (under)galactosylation is a promising biomarker to
      assess disease severity, and monitor and adjust therapy. However, this biomarker
      has not been implemented in routine clinical chemistry because of a complex
      analytical procedure that necessitates IgG purification, which is difficult to
      perform and validate at high throughput. We addressed this issue by using endo
      beta-N-acetylglucosaminidase from Streptococcus pyogenes (endoS) to specifically
      release Fc N-glycans in whole serum. The entire assay can be completed in a few
      hours and only entails adding endoS and labeling the glycans with APTS. Glycans
      are then readily analyzed through capillary electrophoresis. We demonstrate in
      two independent patient cohorts that IgG undergalactosylation levels obtained
      with this assay correlate very well with scores calculated from PNGaseF-released
      glycans of purified antibodies. Our new assay allows to directly and specifically
      measure the degree of IgG galactosylation in serum through a fast and completely
      liquid phase protocol, without the requirement for antibody purification. This
      should help advancing this biomarker toward clinical implementation.

PMID- 30190376
TI  - Cochrane editors hit back at criticisms of HPV vaccine review.

PMID- 30190375
TI  - Inverted repeat structures are associated with essential and highly expressed
      genes on C. elegans autosome distal arms.
AB  - Complementary sequences in cellular transcripts base-pair to form double-stranded
      RNA (dsRNA) structures. Because transposon-derived repeats often give rise to
      self-complementary sequences, dsRNA structures are prevalent in eukaryotic
      genomes, typically occurring in gene introns and untranslated regions (UTRs).
      However, the regulatory impact of double-stranded structures within genes is not
      fully understood. We used three independent methods to define loci in
      Caenorhabditis elegans predicted to form dsRNA and correlated these structures
      with patterns of gene expression, gene essentiality, and genome organization. As
      previously observed, dsRNA loci are enriched on distal arms of C. elegans
      autosomes, where genes typically show less conservation and lower overall
      expression. In contrast, we find that dsRNAs are associated with essential genes
      on autosome arms, and dsRNA-associated genes exhibit higher-than-expected
      expression and histone modification patterns associated with transcriptional
      elongation. Genes with significant repetitive sequence content are also highly
      expressed, and, thus, observed gene expression trends may relate either to dsRNA
      structures or to repeat content. Our results raise the possibility that as-yet
      undescribed mechanisms promote expression of loci that produce dsRNAs, despite
      their well-characterized roles in gene silencing.

PMID- 30190377
TI  - Erratum for the Report "Degradation of microRNAs by a Family of Exoribonucleases
      in Arabidopsis" by V. Ramachandran, X. Chen.

PMID- 30190374
TI  - RNA-Binding Protein RBP-P Is Required for Glutelin and Prolamine mRNA
      Localization in Rice Endosperm Cells.
AB  - In developing rice (Oryza sativa) endosperm, mRNAs of the major storage proteins,
      glutelin and prolamine, are transported and anchored to distinct subdomains of
      the cortical endoplasmic reticulum. RNA binding protein RBP-P binds to both
      glutelin and prolamine mRNAs, suggesting a role in some aspect of their RNA
      metabolism. Here, we show that rice lines expressing mutant RBP-P mislocalize
      both glutelin and prolamine mRNAs. Different mutant RBP-P proteins exhibited
      varying degrees of reduced RNA binding and/or protein-protein interaction
      properties, which may account for the mislocalization of storage protein RNAs. In
      addition, partial loss of RBP-P function conferred a broad phenotypic variation
      ranging from dwarfism, chlorophyll deficiency, and sterility to late flowering
      and low spikelet fertility. Transcriptome analysis highlighted the essential role
      of RBP-P in regulating storage protein genes and several essential biological
      processes during grain development. Overall, our data demonstrate the significant
      roles of RBP-P in glutelin and prolamine mRNA localization and in the regulation
      of genes important for plant growth and development through its RNA binding
      activity and cooperative regulation with interacting proteins.

PMID- 30190378
TI  - Transient phenomena in ecology.
AB  - The importance of transient dynamics in ecological systems and in the models that
      describe them has become increasingly recognized. However, previous work has
      typically treated each instance of these dynamics separately. We review both
      empirical examples and model systems, and outline a classification of transient
      dynamics based on ideas and concepts from dynamical systems theory. This
      classification provides ways to understand the likelihood of transients for
      particular systems, and to guide investigations to determine the timing of sudden
      switches in dynamics and other characteristics of transients. Implications for
      both management and underlying ecological theories emerge.

PMID- 30190380
TI  - New voices, at last.

PMID- 30190381
TI  - News at a glance.

PMID- 30190382
TI  - U.N. tackles gene prospecting on the high seas.

PMID- 30190383
TI  - European funders seek to end reign of paywalled journals.

PMID- 30190385
TI  - In a 'foretold tragedy,' fire consumes Brazil museum.

PMID- 30190379
TI  - Combined adult neurogenesis and BDNF mimic exercise effects on cognition in an
      Alzheimer's mouse model.
AB  - Adult hippocampal neurogenesis (AHN) is impaired before the onset of Alzheimer's
      disease (AD) pathology. We found that exercise provided cognitive benefit to
      5*FAD mice, a mouse model of AD, by inducing AHN and elevating levels of brain
      derived neurotrophic factor (BDNF). Neither stimulation of AHN alone, nor
      exercise, in the absence of increased AHN, ameliorated cognition. We successfully
      mimicked the beneficial effects of exercise on AD mice by genetically and
      pharmacologically inducing AHN in combination with elevating BDNF levels.
      Suppressing AHN later led to worsened cognitive performance and loss of
      preexisting dentate neurons. Thus, pharmacological mimetics of exercise,
      enhancing AHN and elevating BDNF levels, may improve cognition in AD.
      Furthermore, applied at early stages of AD, these mimetics may protect against
      subsequent neuronal cell death.

PMID- 30190384
TI  - 'Rapid onset' of transgender identity ignites storm.

PMID- 30190386
TI  - Renewed sanctions strangle science in Iran.

PMID- 30190387
TI  - Should it be saved?

PMID- 30190388
TI  - How triage became a dirty word.

PMID- 30190389
TI  - Learning to migrate.

PMID- 30190390
TI  - Matchmaking molecule for egg and sperm.

PMID- 30190391
TI  - A brain boost to fight Alzheimer's disease.

PMID- 30190392
TI  - To grow and to defend.

PMID- 30190393
TI  - A radical approach to soot formation.

PMID- 30190394
TI  - Computational astrophysics for the future.

PMID- 30190395
TI  - Denuclearizing North Korea: A verified, phased approach.

PMID- 30190397
TI  - Improving societies' harassment policies.

PMID- 30190396
TI  - Call for new AAAS harassment policy.

PMID- 30190398
TI  - Science engagement in South Africa.

PMID- 30190399
TI  - Resonance-stabilized hydrocarbon-radical chain reactions may explain soot
      inception and growth.
AB  - Mystery surrounds the transition from gas-phase hydrocarbon precursors to
      terrestrial soot and interstellar dust, which are carbonaceous particles formed
      under similar conditions. Although polycyclic aromatic hydrocarbons (PAHs) are
      known precursors to high-temperature carbonaceous-particle formation, the
      molecular pathways that initiate particle formation are unknown. We present
      experimental and theoretical evidence for rapid molecular clustering-reaction
      pathways involving radicals with extended conjugation. These radicals react with
      other hydrocarbon species to form covalently bound complexes that promote further
      growth and clustering by regenerating resonance-stabilized radicals through low
      barrier hydrogen-abstraction and hydrogen-ejection reactions. Such radical-chain
      reaction pathways may lead to covalently bound clusters of PAHs and other
      hydrocarbons that would otherwise be too small to condense at high temperatures,
      thus providing the key mechanistic steps for rapid particle formation and surface
      growth by hydrocarbon chemisorption.

PMID- 30190401
TI  - Zeolitic imidazolate framework membranes made by ligand-induced
      permselectivation.
AB  - Zeolitic imidazolate framework (ZIF) membranes are emerging as a promising energy
      efficient separation technology. However, their reliable and scalable
      manufacturing remains a challenge. We demonstrate the fabrication of ZIF
      nanocomposite membranes by means of an all-vapor-phase processing method based on
      atomic layer deposition (ALD) of ZnO in a porous support followed by ligand-vapor
      treatment. After ALD, the obtained nanocomposite exhibits low flux and is not
      selective, whereas after ligand-vapor (2-methylimidazole) treatment, it is
      partially transformed to ZIF and shows stable performance with high mixture
      separation factor for propylene over propane (an energy-intensive high-volume
      separation) and high propylene flux. Membrane synthesis through ligand-induced
      permselectivation of a nonselective and impermeable deposit is shown to be simple
      and highly reproducible and holds promise for scalability.

PMID- 30190400
TI  - Direct measurements of two-way wave-particle energy transfer in a collisionless
      space plasma.
AB  - Particle acceleration by plasma waves and spontaneous wave generation are
      fundamental energy and momentum exchange processes in collisionless plasmas. Such
      wave-particle interactions occur ubiquitously in space. We present ultrafast
      measurements in Earth's magnetosphere by the Magnetospheric Multiscale spacecraft
      that enabled quantitative evaluation of energy transfer in interactions
      associated with electromagnetic ion cyclotron waves. The observed ion
      distributions are not symmetric around the magnetic field direction but are in
      phase with the plasma wave fields. The wave-ion phase relations demonstrate that
      a cyclotron resonance transferred energy from hot protons to waves, which in turn
      nonresonantly accelerated cold He+ to energies up to ~2 kilo-electron volts.
      These observations provide direct quantitative evidence for collisionless energy
      transfer in plasmas between distinct particle populations via wave-particle
      interactions.

PMID- 30190402
TI  - Regulating the femtosecond excited-state lifetime of a single molecule.
AB  - The key to controlling reactions of molecules induced with the current of a
      scanning tunneling microscope (STM) tip is the ultrashort intermediate excited
      ionic state. The initial condition of the excited state is set by the energy and
      position of the injected current; thereafter, its dynamics determines the
      reaction outcome. We show that a STM can directly and controllably influence the
      excited-state dynamics. For the STM-induced desorption of toluene molecules from
      the Si(111)-7x7 surface, as the tip approaches the molecule, the probability of
      manipulation drops by two orders of magnitude. A two-channel quenching of the
      excited state is proposed, consisting of an invariant surface channel and a tip
      height-dependent channel. We conclude that picometer tip proximity regulates the
      lifetime of the excited state from 10 femtoseconds to less than 0.1 femtoseconds.

PMID- 30190403
TI  - Fast molecular outflow from a dusty star-forming galaxy in the early Universe.
AB  - Galaxies grow inefficiently, with only a small percentage of the available gas
      converted into stars each free-fall time. Feedback processes, such as outflowing
      winds driven by radiation pressure, supernovae, or supermassive black hole
      accretion, can act to halt star formation if they heat or expel the gas supply.
      We report a molecular outflow launched from a dust-rich star-forming galaxy at
      redshift 5.3, 1 billion years after the Big Bang. The outflow reaches velocities
      up to 800 kilometers per second relative to the galaxy, is resolved into multiple
      clumps, and carries mass at a rate within a factor of 2 of the star formation
      rate. Our results show that molecular outflows can remove a large fraction of the
      gas available for star formation from galaxies at high redshift.

PMID- 30190404
TI  - Climate model shows large-scale wind and solar farms in the Sahara increase rain
      and vegetation.
AB  - Wind and solar farms offer a major pathway to clean, renewable energies. However,
      these farms would significantly change land surface properties, and, if
      sufficiently large, the farms may lead to unintended climate consequences. In
      this study, we used a climate model with dynamic vegetation to show that large
      scale installations of wind and solar farms covering the Sahara lead to a local
      temperature increase and more than a twofold precipitation increase, especially
      in the Sahel, through increased surface friction and reduced albedo. The
      resulting increase in vegetation further enhances precipitation, creating a
      positive albedo-precipitation-vegetation feedback that contributes ~80% of the
      precipitation increase for wind farms. This local enhancement is scale dependent
      and is particular to the Sahara, with small impacts in other deserts.

PMID- 30190405
TI  - Is ungulate migration culturally transmitted? Evidence of social learning from
      translocated animals.
AB  - Ungulate migrations are assumed to stem from learning and cultural transmission
      of information regarding seasonal distribution of forage, but this hypothesis has
      not been tested empirically. We compared the migratory propensities of bighorn
      sheep and moose translocated into novel habitats with those of historical
      populations that had persisted for hundreds of years. Whereas individuals from
      historical populations were largely migratory, translocated individuals initially
      were not. After multiple decades, however, translocated populations gained
      knowledge about surfing green waves of forage (tracking plant phenology) and
      increased their propensity to migrate. Our findings indicate that learning and
      cultural transmission are the primary mechanisms by which ungulate migrations
      evolve. Loss of migration will therefore expunge generations of knowledge about
      the locations of high-quality forage and likely suppress population abundance.

PMID- 30190406
TI  - A single transcription factor promotes both yield and immunity in rice.
AB  - Plant immunity often penalizes growth and yield. The transcription factor Ideal
      Plant Architecture 1 (IPA1) reduces unproductive tillers and increases grains per
      panicle, which results in improved rice yield. Here we report that higher IPA1
      levels enhance immunity. Mechanistically, phosphorylation of IPA1 at amino acid
      Ser163 within its DNA binding domain occurs in response to infection by the
      fungus Magnaporthe oryzae and alters the DNA binding specificity of IPA1.
      Phosphorylated IPA1 binds to the promoter of the pathogen defense gene WRKY45 and
      activates its expression, leading to enhanced disease resistance. IPA1 returns to
      a nonphosphorylated state within 48 hours after infection, resuming support of
      the growth needed for high yield. Thus, IPA1 promotes both yield and disease
      resistance by sustaining a balance between growth and immunity.

PMID- 30190407
TI  - The Ly6/uPAR protein Bouncer is necessary and sufficient for species-specific
      fertilization.
AB  - Fertilization is fundamental for sexual reproduction, yet its molecular
      mechanisms are poorly understood. We found that an oocyte-expressed Ly6/uPAR
      protein, which we call Bouncer, is a crucial fertilization factor in zebrafish.
      Membrane-bound Bouncer mediates sperm-egg binding and is thus essential for sperm
      entry into the egg. Remarkably, Bouncer not only is required for sperm-egg
      interaction but is also sufficient to allow cross-species fertilization between
      zebrafish and medaka, two fish species that diverged more than 200 million years
      ago. Our study thus identifies Bouncer as a key determinant of species-specific
      fertilization in fish. Bouncer's closest homolog in tetrapods, SPACA4, is
      restricted to the male germline in internally fertilizing vertebrates, which
      suggests that our findings in fish have relevance to human biology.

PMID- 30190409
TI  - Outsmarting our instruments.

PMID- 30190410
TI  - Solution must be found for L116m cost of outsourcing scans, says radiologists'
      president.

PMID- 30190408
TI  - Minimal functional driver gene heterogeneity among untreated metastases.
AB  - Metastases are responsible for the majority of cancer-related deaths. Although
      genomic heterogeneity within primary tumors is associated with relapse,
      heterogeneity among treatment-naive metastases has not been comprehensively
      assessed. We analyzed sequencing data for 76 untreated metastases from 20
      patients and inferred cancer phylogenies for breast, colorectal, endometrial,
      gastric, lung, melanoma, pancreatic, and prostate cancers. We found that within
      individual patients, a large majority of driver gene mutations are common to all
      metastases. Further analysis revealed that the driver gene mutations that were
      not shared by all metastases are unlikely to have functional consequences. A
      mathematical model of tumor evolution and metastasis formation provides an
      explanation for the observed driver gene homogeneity. Thus, single biopsies
      capture most of the functionally important mutations in metastases and therefore
      provide essential information for therapeutic decision-making.

PMID- 30190411
TI  - Statins don't reduce cardiovascular disease or death in healthy over 75s, study
      finds.

PMID- 30190413
TI  - Early Appearance and Spread of Fast Ripples in the Hippocampus in a Model of
      Cortical Traumatic Brain Injury.
AB  - Fast ripples (FRs; activity of >250 Hz) have been considered as a biomarker of
      epileptic activity in the hippocampus and entorhinal cortex; it is thought that
      they signal the focus of seizure generation. Similar high-frequency network
      activity has been produced in vitro by changing extracellular medium composition,
      by using pro-epileptic substances, or by electrical stimulation. Here we study
      the propagation of these events between different subregions of the male rat
      hippocampus in a recently introduced experimental model of FRs in entorhinal
      cortex-hippocampal slices in vitro By using a matrix of 4096 microelectrodes, the
      sites of initiation, propagation pathways, and spatiotemporal characteristics of
      activity patterns could be studied with unprecedented high resolution. To this
      end, we developed an analytic tool based on bidimensional current source density
      estimation, which delimits sinks and sources with a high precision and evaluates
      their trajectories using the concept of center of mass. With this methodology, we
      found that FRs can arise almost simultaneously at noncontiguous sites in the CA3
      to-CA1 direction, underlying the spatial heterogeneity of epileptogenic foci,
      while continuous somatodendritic waves of activity develop. An unexpected, yet
      important propagation route is the propagation of activity from CA3 into the
      hilus and dentate gyrus. This pathway may cause reverberating activation of both
      regions, supporting sustained pathological network events and altered information
      processing in hippocampal networks.SIGNIFICANCE STATEMENT Fast ripples (FRs) have
      been considered as a biomarker of epileptic activity and may signal the focus of
      seizure generation. In a model of traumatic brain injury in the rat, FRs appear
      in the hippocampus within a couple of hours after an extrahippocampal, cortical
      lesion. We analyzed the origin and dynamics of the FRs in the hippocampus using
      massive electrophysiological recordings, allowing an unprecedented high
      spatiotemporal resolution. We show that FRs originate in distinct and
      noncontiguous locations within the CA3 region and uncover, with high precision,
      the extent and dynamics of their current density. This activity propagates toward
      CA1 but also backpropagates to the hilus and the dentate gyrus, suggesting
      activation of defined microcircuits that can sustain recurrent excitation.

PMID- 30190414
TI  - Head-mounted sensors reveal visual attention of free-flying homing pigeons.
AB  - Gaze behavior offers valuable insights into attention and cognition. However,
      technological limitations have prevented the examination of animals' gaze
      behavior in natural, information-rich contexts; for example, during navigation
      through complex environments. Therefore, we developed a lightweight custom-made
      logger equipped with an inertial measurement unit (IMU) and GPS to simultaneously
      track the head movements and flight trajectories of free-flying homing pigeons.
      Pigeons have a limited range of eye movement, and their eye moves in coordination
      with their head in a saccadic manner (similar to primate eye saccades). This
      allows head movement to act as a proxy for visual scanning behavior. Our IMU
      sensor recorded the 3D movement of the birds' heads in high resolution, allowing
      us to reliably detect distinct saccade signals. The birds moved their head far
      more than necessary for maneuvering flight, suggesting that they actively scanned
      the environment. This movement was predominantly horizontal (yaw) and sideways
      (roll), allowing them to scan the environment with their lateral visual field.
      They decreased their head movement when they flew solo over prominent landmarks
      (major roads and a railway line) and also when they flew in pairs (especially
      when flying side by side, with the partner maintained in their lateral visual
      field). Thus, a decrease in head movement indicates a change in birds' focus of
      attention. We conclude that pigeons use their head gaze in a task-related manner
      and that tracking flying birds' head movement is a promising method for examining
      their visual attention during natural tasks.

PMID- 30190412
TI  - The Divalent Metal Transporter 1 (DMT1) Is Required for Iron Uptake and Normal
      Development of Oligodendrocyte Progenitor Cells.
AB  - The divalent metal transporter 1 (DMT1) is a multimetal transporter with a
      primary role in iron transport. Although DMT1 has been described previously in
      the CNS, nothing was known about the role of this metal transporter in
      oligodendrocyte maturation and myelination. To determine whether DMT1 is required
      for oligodendrocyte progenitor cell (OPC) maturation, we used siRNAs and the Cre
      lox system to knock down/knock out DMT1 expression in vitro as well as in vivo
      Blocking DMT1 synthesis in primary cultures of OPCs reduced oligodendrocyte iron
      uptake and significantly delayed OPC development. In vivo, a significant
      hypomyelination was found in DMT1 conditional knock-out mice in which DMT1 was
      postnatally deleted in NG2- or Sox10-positive OPCs. The brain of DMT1 knock-out
      animals presented a decrease in the expression levels of myelin proteins and a
      substantial reduction in the percentage of myelinated axons. This reduced
      postnatal myelination was accompanied by a decrease in the number of myelinating
      oligodendrocytes and a rise in proliferating OPCs. Furthermore, using the
      cuprizone model of demyelination, we established that DMT1 deletion in NG2
      positive OPCs lead to less efficient remyelination of the adult brain. These
      results indicate that DMT1 is vital for OPC maturation and for the normal
      myelination of the mouse brain.SIGNIFICANCE STATEMENT To determine whether
      divalent metal transporter 1 (DMT1), a multimetal transporter with a primary role
      in iron transport, is essential for oligodendrocyte development, we created two
      conditional knock-out mice in which DMT1 was postnatally deleted in NG2- or Sox10
      positive oligodendrocyte progenitor cells (OPCs). We have established that DMT1
      is necessary for normal OPC maturation and is required for an efficient
      remyelination of the adult brain. Since iron accumulation by OPCs is
      indispensable for myelination, understanding the iron incorporation mechanism as
      well as the molecules involved is critical to design new therapeutic approaches
      to intervene in diseases in which the myelin sheath is damaged or lost.

PMID- 30190415
TI  - Rethinking the evolution of the human foot: insights from experimental research.
AB  - Adaptive explanations for modern human foot anatomy have long fascinated
      evolutionary biologists because of the dramatic differences between our feet and
      those of our closest living relatives, the great apes. Morphological features,
      including hallucal opposability, toe length and the longitudinal arch, have
      traditionally been used to dichotomize human and great ape feet as being adapted
      for bipedal walking and arboreal locomotion, respectively. However, recent
      biomechanical models of human foot function and experimental investigations of
      great ape locomotion have undermined this simple dichotomy. Here, we review this
      research, focusing on the biomechanics of foot strike, push-off and elastic
      energy storage in the foot, and show that humans and great apes share some
      underappreciated, surprising similarities in foot function, such as use of
      plantigrady and ability to stiffen the midfoot. We also show that several unique
      features of the human foot, including a spring-like longitudinal arch and short
      toes, are likely adaptations to long distance running. We use this framework to
      interpret the fossil record and argue that the human foot passed through three
      evolutionary stages: first, a great ape-like foot adapted for arboreal locomotion
      but with some adaptations for bipedal walking; second, a foot adapted for
      effective bipedal walking but retaining some arboreal grasping adaptations; and
      third, a human-like foot adapted for enhanced economy during long-distance
      walking and running that had lost its prehensility. Based on this scenario, we
      suggest that selection for bipedal running played a major role in the loss of
      arboreal adaptations.

PMID- 30190416
TI  - Correction: The reluctant visitor: an alkaloid in toxic nectar can reduce
      olfactory learning and memory in Asian honey bees (doi:10.1242/jeb.168344).

PMID- 30190417
TI  - The Spermine Synthase OsSPMS1 Regulates Seed Germination, Grain Size, and Yield.
AB  - Polyamines, including putrescine (Put), spermidine (Spd), and spermine (Spm),
      play essential roles in a wide variety of prokaryotic and eukaryotic organisms.
      Rice (Oryza sativa) contains four putative spermidine/spermine synthase (SPMS)
      encoding genes (OsSPMS1, OsSPMS2, OsSPMS3, and OsACAULIS5), but none have been
      functionally characterized. In this study, we used a reverse genetic strategy to
      investigate the biological function of OsSPMS1. We generated several homozygous
      RNA interference (RNAi) and overexpression (OE) lines of OsSPMS1. Phenotypic
      analysis indicated that OsSPMS1 negatively regulates seed germination, grain
      size, and grain yield per plant. The ratio of Spm to Spd was significantly lower
      in the RNAi lines and considerably higher in the OE lines than in the wild-type
      (WT), suggesting that OsSPMS1 may function as a spermine synthase. S-adenosyl-L
      methionine is a common precursor of polyamines and ethylene biosynthesis. The 1
      aminocyclopropane-1-carboxylic acid (ACC) and ethylene contents in seeds
      significantly increased in RNAi lines and decreased in OE lines, respectively,
      compared with wild-type. Additionally, the reduced germination rates and growth
      defects of OE lines could be rescued with ACC treatment. These data suggest that
      OsSPMS1 affects ethylene synthesis and may regulate seed germination and plant
      growth by affecting the ACC and ethylene pathways. Most importantly, an OsSPMS1
      knockout mutant showed an increase in grain yield per plant in a high-yield
      variety, Suken118, suggesting that OsSPMS1 is an important target for yield
      enhancement in rice.

PMID- 30190418
TI  - MdMYB88 and MdMYB124 Enhance Drought Tolerance by Modulating Root Vessels and
      Cell Walls in Apple.
AB  - Water deficit is one of the main limiting factors in apple (Malus * domestica
      Borkh.) cultivation. Root architecture plays an important role in the drought
      tolerance of plants; however, research efforts to improve drought tolerance of
      apple trees have focused on aboveground targets. Due to the difficulties
      associated with visualization and data analysis, there is currently a poor
      understanding of the genetic players and molecular mechanisms involved in the
      root architecture of apple trees under drought conditions. We previously observed
      that MdMYB88 and its paralog MdMYB124 regulate apple tree root morphology. In
      this study, we found that MdMYB88 and MdMYB124 play important roles in
      maintaining root hydraulic conductivity under long-term drought conditions and
      therefore contribute toward adaptive drought tolerance. Further investigation
      revealed that MdMYB88 and MdMYB124 regulate root xylem development by directly
      binding MdVND6 and MdMYB46 promoters and thus influence expression of their
      target genes under drought conditions. In addition, MdMYB88 and MdMYB124 were
      shown to regulate the deposition of cellulose and lignin root cell walls in
      response to drought. Taken together, our results provide novel insights into the
      importance of MdMYB88 and MdMYB124 in root architecture, root xylem development,
      and secondary cell wall deposition in response to drought in apple trees.

PMID- 30190419
TI  - Early Senescence in Older Leaves of Low Nitrate-Grown Atxdh1 Uncovers a Role for
      Purine Catabolism in N Supply.
AB  - The nitrogen (N)-rich ureides allantoin and allantoate, which are products of
      purine catabolism, play a role in N delivery in Leguminosae. Here, we examined
      their role as an N source in nonlegume plants using Arabidopsis (Arabidopsis
      thaliana) plants mutated in XANTHINE DEHYDROGENASE1 (AtXDH1), a catalytic
      bottleneck in purine catabolism. Older leaves of the Atxdh1 mutant exhibited
      early senescence, lower soluble protein, and lower organic N levels as compared
      with wild-type older leaves when grown with 1 mm nitrate but were comparable to
      the wild type under 5 mm nitrate. Similar nitrate-dependent senescence phenotypes
      were evident in the older leaves of allantoinase (Ataln) and allantoate
      amidohydrolase (Ataah) mutants, which also are impaired in purine catabolism.
      Under low-nitrate conditions, xanthine accumulated in older leaves of Atxdh1,
      whereas allantoin accumulated in both older and younger leaves of Ataln but not
      in wild-type leaves, indicating the remobilization of xanthine-degraded products
      from older to younger leaves. Supporting this notion, ureide transporter
      expression was enhanced in older leaves of the wild type in low-nitrate as
      compared with high-nitrate conditions. Elevated transcripts and proteins of AtXDH
      and AtAAH were detected in low-nitrate-grown wild-type plants, indicating
      regulation at protein and transcript levels. The higher nitrate reductase
      activity in Atxdh1 leaves compared with wild-type leaves indicated a need for
      nitrate assimilation products. Together, these results indicate that the absence
      of remobilized purine-degraded N from older leaves of Atxdh1 caused senescence
      symptoms, a result of higher chloroplastic protein degradation in older leaves of
      low-nitrate-grown plants.

PMID- 30190420
TI  - Signatures of Insecticide Selection in the Genome of Drosophila melanogaster.
AB  - Resistance to insecticides has evolved in multiple insect species, leading to
      increased application rates and even control failures. Understanding the genetic
      basis of insecticide resistance is fundamental for mitigating its impact on crop
      production and disease control. We performed a GWAS approach with the Drosophila
      Genetic Reference Panel (DGRP) to identify the mutations involved in resistance
      to two widely used classes of insecticides: organophosphates (OPs, parathion) and
      pyrethroids (deltamethrin). Most variation in parathion resistance was associated
      with mutations in the target gene Ace, while most variation in deltamethrin
      resistance was associated with mutations in Cyp6a23, a gene encoding a
      detoxification enzyme never previously associated with resistance. A "nested
      GWAS" further revealed the contribution of other loci: Dscam1 and trpl were
      implicated in resistance to parathion, but only in lines lacking Wolbachia
      Cyp6a17, the paralogous gene of Cyp6a23, and CG7627, an ATP-binding cassette
      transporter, were implicated in deltamethrin resistance. We observed signatures
      of recent selective sweeps at all of these resistance loci and confirmed that the
      soft sweep at Ace is indeed driven by the identified resistance mutations.
      Analysis of allele frequencies in additional population samples revealed that
      most resistance mutations are segregating across the globe, but that frequencies
      can vary substantially among populations. Altogether, our data reveal that the
      widely used OP and pyrethroid insecticides imposed a strong selection pressure on
      natural insect populations. However, it remains unclear why, in Drosophila,
      resistance evolved due to changes in the target site for OPs, but due to a
      detoxification enzyme for pyrethroids.

PMID- 30190421
TI  - Structural Variants and Selective Sweep Foci Contribute to Insecticide Resistance
      in the Drosophila Genetic Reference Panel.
AB  - Patterns of nucleotide polymorphism within populations of Drosophila melanogaster
      suggest that insecticides have been the selective agents driving the strongest
      recent bouts of positive selection. However, there is a need to explicitly link
      selective sweeps to the particular insecticide phenotypes that could plausibly
      account for the drastic selective responses that are observed in these non-target
      insects. Here, we screen the Drosophila Genetic Reference Panel with two common
      insecticides; malathion (an organophosphate) and permethrin (a pyrethroid).
      Genome-wide association studies map survival on malathion to two of the largest
      sweeps in the D. melanogaster genome; Ace and Cyp6g1 Malathion survivorship also
      correlates with lines which have high levels of Cyp12d1, Jheh1 and Jheh2
      transcript abundance. Permethrin phenotypes map to the largest cluster of P450
      genes in the Drosophila genome, however in contrast to a selective sweep driven
      by insecticide use, the derived allele seems to be associated with
      susceptibility. These results underscore previous findings that highlight the
      importance of structural variation to insecticide phenotypes: Cyp6g1 exhibits
      copy number variation and transposable element insertions, Cyp12d1 is tandemly
      duplicated, the Jheh loci are associated with a Bari1 transposable element
      insertion, and a Cyp6a17 deletion is associated with susceptibility.

PMID- 30190422
TI  - Mechanisms Behind Resistance to PI3K Inhibitor Treatment Induced by the PIM
      Kinase.
AB  - Cancer resistance to PI3K inhibitor therapy can be in part mediated by increases
      in the PIM1 kinase. However, the exact mechanism by which PIM kinase promotes
      tumor cell resistance is unknown. Our study unveils the pivotal control of redox
      signaling by PIM kinases as a driver of this resistance mechanism. PIM1 kinase
      functions to decrease cellular ROS levels by enhancing nuclear factor erythroid 2
      related factor 2 (NRF2)/antioxidant response element activity. PIM prevents cell
      death induced by PI3K-AKT-inhibitory drugs through a noncanonical mechanism of
      NRF2 ubiquitination and degradation and translational control of NRF2 protein
      levels through modulation of eIF4B and mTORC1 activity. Importantly, PIM also
      controls NAD(P)H production by increasing glucose flux through the pentose
      phosphate shunt decreasing ROS production, and thereby diminishing the
      cytotoxicity of PI3K-AKT inhibitors. Treatment with PIM kinase inhibitors
      reverses this resistance phenotype, making tumors increasingly susceptible to
      small-molecule therapeutics, which block the PI3K-AKT pathway.

PMID- 30190423
TI  - Selective Inhibition of ADAM28 Suppresses Lung Carcinoma Cell Growth and
      Metastasis.
AB  - ADAM28 (a disintegrin and metalloproteinase 28) is overexpressed by carcinoma
      cells in non-small cell lung carcinomas (NSCLC) and plays an important role in
      cancer cell proliferation and metastasis by reactivation of insulin-like growth
      factor-1 (IGF-1) and escaping from von Willebrand factor (VWF)-induced apoptosis
      through digestion of IGF-binding protein-3 and VWF, respectively. To aim for new
      target therapy of NSCLC patients, we developed human neutralizing antibodies 211
      12 and 211-14 against ADAM28, which showed IC50 values of 62.4 and 37.5 nmol/L,
      respectively. Antibody 211-14 recognized the junctional region between cysteine
      rich domain and secreted-specific domain and showed a KD value of 94.7 pmol/L for
      the epitope-containing peptide. This antibody detected monkey and human secreted
      form ADAM28s, although it was not reactive with mouse membrane-anchored ADAM28m.
      Antibody 211-14 effectively inhibited IGF-1-stimulated cell proliferation of lung
      adenocarcinoma cell lines with ADAM28 expression, including PC-9 cells, and
      promoted VWF-induced cell death in these cell lines. In lung metastasis models,
      antibody 211-14 significantly reduced tumor growth and metastases of PC-9 cells
      and prolonged survivals in the antibody-treated mice compared with the control
      IgG-treated ones. Combination therapy of the antibody and docetaxel was more
      effective than that of bevacizumab and docetaxel and showed further elongation of
      survival time compared with monotherapy. No adverse effects were observed even
      after administration of 10-fold more than effective dose of anti-ADAM28 antibody
      to normal mice. Our data demonstrate that antibody 211-14 is a neutralizing
      antibody specific to ADAM28s and suggest that this antibody may be a useful
      treatment remedy for NSCLC patients. Mol Cancer Ther; 17(11); 2427-38. (c)2018
      AACR.

PMID- 30190424
TI  - Interleukin-24 (IL24) Is Suppressed by PAX3-FOXO1 and Is a Novel Therapy for
      Rhabdomyosarcoma.
AB  - Alveolar rhabdomyosarcoma (ARMS) patients have a poor prognosis, and this is
      primarily due to overexpression of the oncogenic fusion protein PAX3-FOXO1.
      Results of RNA-sequencing studies show that PAX3-FOXO1 represses expression of
      interleukin-24 (IL24), and these two genes are inversely expressed in patient
      tumors. PAX3-FOXO1 also regulates histone deacetylase 5 (HDAC5) in ARMS cells,
      and results of RNA interference studies confirmed that PAX3-FOXO1-mediated
      repression of IL24 is HDAC5-dependent. Knockdown of PAX3-FOXO1 decreases ARMS
      cell proliferation, survival, and migration, and we also observed similar
      responses in cells after overexpression of IL24, consistent with results reported
      for this tumor suppressor-like cytokine in other solid tumors. We also observed
      in double knockdown studies that the inhibition of ARMS cell proliferation,
      survival, and migration after knockdown of PAX3-FOXO1 was significantly (>75%)
      reversed by knockdown of IL24. Adenoviral-expressed IL24 was directly injected
      into ARMS tumors in athymic nude mice, and this resulted in decreased tumor
      growth and weight. Because adenoviral IL24 has already successfully undergone
      phase I in clinical trials, this represents an alternative approach (alone and/or
      combination) for treating ARMS patients who currently undergo cytotoxic drug
      therapies.

PMID- 30190425
TI  - GEF mechanism revealed by the structure of SmgGDS-558 and farnesylated RhoA
      complex and its implication for a chaperone mechanism.
AB  - SmgGDS has dual functions in cells and regulates small GTPases as both a guanine
      nucleotide exchange factor (GEF) for the Rho family and a molecular chaperone for
      small GTPases possessing a C-terminal polybasic region followed by four C
      terminal residues called the CaaX motif, which is posttranslationally prenylated
      at its cysteine residue. Our recent structural work revealed that SmgGDS folds
      into tandem copies of armadillo-repeat motifs (ARMs) that are not present in
      other GEFs. However, the precise mechanism of GEF activity and recognition
      mechanism for the prenylated CaaX motif remain unknown because SmgGDS does not
      have a typical GEF catalytic domain and lacks a pocket to accommodate a prenyl
      group. Here, we aimed to determine the crystal structure of the
      SmgGDS/farnesylated RhoA complex. We found that SmgGDS induces a significant
      conformational change in the switch I and II regions that opens up the nucleotide
      binding site, with the prenyl group fitting into the cryptic pocket in the N
      terminal ARMs. Taken together, our findings could advance the understanding of
      the role of SmgGDS and enable drug design strategies for targeting SmgGDS and
      small GTPases.

PMID- 30190426
TI  - Pathogens' adaptation to the human host.

PMID- 30190428
TI  - Death of Mycobacterium tuberculosis by l-arginine starvation.

PMID- 30190427
TI  - Photoaffinity-engineered protein scaffold for systematically exploring native
      phosphotyrosine signaling complexes in tumor samples.
AB  - Phosphotyrosine (pTyr)-regulated protein complexes play critical roles in cancer
      signaling. The systematic characterization of these protein complexes in tumor
      samples remains a challenge due to their limited access and the transient nature
      of pTyr-mediated interactions. We developed a hybrid chemical proteomics
      approach, termed Photo-pTyr-scaffold, by engineering Src homology 2 (SH2)
      domains, which specifically bind pTyr proteins, with both trifunctional chemical
      probes and genetic mutations to overcome these challenges. Dynamic SH2 domain
      scaffolding protein complexes were efficiently cross-linked under mild UV light,
      captured by biotin tag, and identified by mass spectrometry. This approach was
      successfully used to profile native pTyr protein complexes from breast cancer
      tissue samples on a proteome scale with high selectivity, achieving about 100
      times higher sensitivity for detecting pTyr signaling proteins than that afforded
      by traditional immunohistochemical methods. Among more than 1,000 identified pTyr
      proteins, receptor tyrosine kinase PDGFRB expressed on cancer-associated
      fibroblasts was validated as an important intercellular signaling regulator with
      poor expression correlation to ERBB2, and blockade of PDGFRB signaling could
      efficiently suppress tumor growth. The Photo-pTyr-scaffold approach may become a
      generic tool for readily profiling dynamic pTyr signaling complexes in clinically
      relevant samples.

PMID- 30190429
TI  - Simultaneous polymerization and adhesion under hypoxia in sickle cell disease.
AB  - Polymerization and adhesion, dynamic processes that are hallmarks of sickle cell
      disease (SCD), have thus far been studied in vitro only separately. Here, we
      present quantitative results of the simultaneous and synergistic effects of
      adhesion and polymerization of deoxygenated sickle hemoglobin (HbS) in the human
      red blood cell (RBC) on the mechanisms underlying vasoocclusive pain crisis. For
      this purpose, we employ a specially developed hypoxic microfluidic platform,
      which is capable of inducing sickling and unsickling of RBCs in vitro, to test
      blood samples from eight patients with SCD. We supplemented these experimental
      results with detailed molecular-level computational simulations of cytoadherence
      and biorheology using dissipative particle dynamics. By recourse to image
      analysis techniques, we characterize sickle RBC maturation stages in the
      following order of the degree of adhesion susceptibility under hypoxia: sickle
      reticulocytes in circulation (SRs) -> sickle mature erythrocytes (SMEs) ->
      irreversibly sickled cells (ISCs). We show that (i) hypoxia significantly
      enhances sickle RBC adherence; (ii) HbS polymerization enhances sickle cell
      adherence in SRs and SMEs, but not in ISCs; (iii) SRs exhibit unique adhesion
      dynamics where HbS fiber projections growing outward from the cell surface create
      multiple sites of adhesion; and (iv) polymerization stimulates adhesion and vice
      versa, thereby establishing the bidirectional coupling between the two processes.
      These findings offer insights into possible mechanistic pathways leading to
      vasoocclusion crisis. They also elucidate the processes underlying the onset of
      occlusion that may involve circulating reticulocytes, which are more abundant in
      hemolytic anemias due to robust compensatory erythropoiesis.

PMID- 30190431
TI  - Building immune tolerance through DNA vaccination.

PMID- 30190430
TI  - Membrane-wrapped nanoparticles probe divergent roles of GM3 and
      phosphatidylserine in lipid-mediated viral entry pathways.
AB  - Gold nanoparticles (NPs) wrapped in a membrane can be utilized as artificial
      virus nanoparticles (AVNs) that combine the large nonblinking or bleaching
      optical cross-section of the NP core with the biological surface properties and
      functionalities provided by a self-assembled lipid membrane. We used these hybrid
      nanomaterials to test the roles of monosialodihexosylganglioside (GM3) and
      phosphatidylserine (PS) for a lipid-mediated targeting of virus-containing
      compartments (VCCs) in macrophages. GM3-presenting AVNs bind to CD169 (Siglec-1)
      expressing macrophages, but inclusion of PS in the GM3-containing AVN membrane
      decreases binding. Molecular dynamics simulations of the AVN membrane and
      experimental binding studies of CD169 to GM3-presenting AVNs reveal Na+-mediated
      interactions between GM3 and PS as a potential cause of the antagonistic action
      on binding by the two negatively charged lipids. GM3-functionalized AVNs with no
      or low PS content localize to tetherin+, CD9+ VCC in a membrane composition
      depending fashion, but increasing amounts of PS in the AVN membrane redirect the
      NP to lysosomal compartments. Interestingly, this compartmentalization is highly
      GM3 specific. Even AVNs presenting the related monosialotetrahexosylganglioside
      (GM1) fail to achieve an accumulation in VCC. AVN localization to VCC was
      observed for AVN with gold NP core but not for liposomes, suggesting that NP
      sequestration into VCC has additional requirements beyond ligand (GM3)-receptor
      (CD169) recognition that are related to the physical properties of the NP core.
      Our results confirm AVN as a scalable platform for elucidating the mechanisms of
      lipid-mediated viral entry pathways and for selective intracellular targeting.

PMID- 30190433
TI  - Toward the first quantum simulation with quantum speedup.
AB  - With quantum computers of significant size now on the horizon, we should
      understand how to best exploit their initially limited abilities. To this end, we
      aim to identify a practical problem that is beyond the reach of current classical
      computers, but that requires the fewest resources for a quantum computer. We
      consider quantum simulation of spin systems, which could be applied to understand
      condensed matter phenomena. We synthesize explicit circuits for three leading
      quantum simulation algorithms, using diverse techniques to tighten error bounds
      and optimize circuit implementations. Quantum signal processing appears to be
      preferred among algorithms with rigorous performance guarantees, whereas higher
      order product formulas prevail if empirical error estimates suffice. Our circuits
      are orders of magnitude smaller than those for the simplest classically
      infeasible instances of factoring and quantum chemistry, bringing practical
      quantum computation closer to reality.

PMID- 30190432
TI  - CAMSAP3 maintains neuronal polarity through regulation of microtubule stability.
AB  - The molecular mechanisms that guide each neuron to become polarized, forming a
      single axon and multiple dendrites, remain unknown. Here we show that CAMSAP3
      (calmodulin-regulated spectrin-associated protein 3), a protein that regulates
      the minus-end dynamics of microtubules, plays a key role in maintaining neuronal
      polarity. In mouse hippocampal neurons, CAMSAP3 was enriched in axons. Although
      axonal microtubules were generally acetylated, CAMSAP3 was preferentially
      localized along a less-acetylated fraction of the microtubules. CAMSAP3-mutated
      neurons often exhibited supernumerary axons, along with an increased number of
      neurites having nocodazole-resistant/acetylated microtubules compared with wild
      type neurons. Analysis using cell lines showed that CAMSAP3 depletion promoted
      tubulin acetylation, and conversely, mild overexpression of CAMSAP3 inhibited it,
      suggesting that CAMSAP3 works to retain nonacetylated microtubules. In contrast,
      CAMSAP2, a protein related to CAMSAP3, was detected along all neurites, and its
      loss did not affect neuronal polarity, nor did it cause increased tubulin
      acetylation. Depletion of alpha-tubulin acetyltransferase-1 (alphaTAT1), the key
      enzyme for tubulin acetylation, abolished CAMSAP3 loss-dependent multiple-axon
      formation. These observations suggest that CAMSAP3 sustains a nonacetylated pool
      of microtubules in axons, interfering with the action of alphaTAT1, and this
      process is important to maintain neuronal polarity.

PMID- 30190434
TI  - A plant-responsive bacterial-signaling system senses an ethanolamine derivative.
AB  - Certain plant-associated Proteobacteria sense their host environment by detecting
      an unknown plant signal recognized by a member of a LuxR subfamily of
      transcription factors. This interkingdom communication is important for both
      mutualistic and pathogenic interactions. The Populus root endophyte Pseudomonas
      sp. GM79 possesses such a regulator, named PipR. In a previous study we reported
      that PipR activates an adjacent gene (pipA) coding for a proline iminopeptidase
      in response to Populus leaf macerates and peptides and that this activation is
      dependent on a putative ABC-type transporter [Schaefer AL, et al. (2016) mBio
      7:e01101-16]. In this study we identify a chemical derived from ethanolamine that
      induces PipR activity at picomolar concentrations, and we present evidence that
      this is the active inducer present in plant leaf macerates. First, a screen of
      more than 750 compounds indicated ethanolamine was a potent inducer for the PipR
      sensing system; however, ethanolamine failed to bind to the periplasmic-binding
      protein (PBP) required for the signal response. This led us to discover that a
      specific ethanolamine derivative, N-(2-hydroxyethyl)-2-(2-hydroxyethylamino)
      acetamide (HEHEAA), binds to the PBP and serves as a potent PipR-dependent
      inducer. We also show that a compound, which coelutes with HEHEAA in HPLC and
      induces pipA gene expression in a PipR-dependent manner, can be found in Populus
      leaf macerates. This work sheds light on how plant-associated bacteria can sense
      their environment and on the nature of inducers for a family of plant-responsive
      LuxR-like transcription factors found in plant-associated bacteria.

PMID- 30190437
TI  - Deep learning to represent subgrid processes in climate models.
AB  - The representation of nonlinear subgrid processes, especially clouds, has been a
      major source of uncertainty in climate models for decades. Cloud-resolving models
      better represent many of these processes and can now be run globally but only for
      short-term simulations of at most a few years because of computational
      limitations. Here we demonstrate that deep learning can be used to capture many
      advantages of cloud-resolving modeling at a fraction of the computational cost.
      We train a deep neural network to represent all atmospheric subgrid processes in
      a climate model by learning from a multiscale model in which convection is
      treated explicitly. The trained neural network then replaces the traditional
      subgrid parameterizations in a global general circulation model in which it
      freely interacts with the resolved dynamics and the surface-flux scheme. The
      prognostic multiyear simulations are stable and closely reproduce not only the
      mean climate of the cloud-resolving simulation but also key aspects of
      variability, including precipitation extremes and the equatorial wave spectrum.
      Furthermore, the neural network approximately conserves energy despite not being
      explicitly instructed to. Finally, we show that the neural network
      parameterization generalizes to new surface forcing patterns but struggles to
      cope with temperatures far outside its training manifold. Our results show the
      feasibility of using deep learning for climate model parameterization. In a
      broader context, we anticipate that data-driven Earth system model development
      could play a key role in reducing climate prediction uncertainty in the coming
      decade.

PMID- 30190435
TI  - Structural basis for activation of voltage sensor domains in an ion channel TPC1.
AB  - Voltage-sensing domains (VSDs) couple changes in transmembrane electrical
      potential to conformational changes that regulate ion conductance through a
      central channel. Positively charged amino acids inside each sensor cooperatively
      respond to changes in voltage. Our previous structure of a TPC1 channel captured
      an example of a resting-state VSD in an intact ion channel. To generate an
      activated-state VSD in the same channel we removed the luminal inhibitory Ca2+
      binding site (Cai2+), which shifts voltage-dependent opening to more negative
      voltage and activation at 0 mV. Cryo-EM reveals two coexisting structures of the
      VSD, an intermediate state 1 that partially closes access to the cytoplasmic side
      but remains occluded on the luminal side and an intermediate activated state 2 in
      which the cytoplasmic solvent access to the gating charges closes, while luminal
      access partially opens. Activation can be thought of as moving a hydrophobic
      insulating region of the VSD from the external side to an alternate grouping on
      the internal side. This effectively moves the gating charges from the inside
      potential to that of the outside. Activation also requires binding of Ca2+ to a
      cytoplasmic site (Caa2+). An X-ray structure with Caa2+ removed and a near-atomic
      resolution cryo-EM structure with Cai2+ removed define how dramatic
      conformational changes in the cytoplasmic domains may communicate with the VSD
      during activation. Together four structures provide a basis for understanding the
      voltage-dependent transition from resting to activated state, the tuning of VSD
      by thermodynamic stability, and this channel's requirement of cytoplasmic Ca2+
      ions for activation.

PMID- 30190438
TI  - Phosphatase 1 Nuclear Targeting Subunit (PNUTS) Regulates Aurora Kinases and
      Mitotic Progression.
AB  - Mitotic progression is regulated largely by reversible phosphorylation events
      that are mediated by mitotic kinases and phosphatases. Protein phosphatase 1
      (PP1) has been shown to play a crucial role in regulation of mitotic entry,
      progression, and exit. We previously observed, in Xenopus egg extracts, that
      phosphatase 1 nuclear targeting subunit (PPP1R10/PNUTS) acts as a mitotic
      regulator by negatively modulating PP1. This study investigates the role of PNUTS
      in mitotic progression in mammalian cells, and demonstrates that PNUTS expression
      is elevated in mitosis and depletion partially blocks mitotic entry. Cells that
      enter mitosis after PNUTS knockdown exhibit frequent chromosome mis-segregation.
      Aurora A/B kinase complexes and several kinetochore components are identified as
      PNUTS-associated proteins. PNUTS depletion suppresses the activation of Aurora
      A/B kinases, and disrupts the spatiotemporal regulation of the chromosomal
      passenger complex (CPC). PNUTS dynamically localizes to kinetochores, and is
      required for the activation of the spindle assembly checkpoint. Finally, PNUTS
      depletion sensitizes the tumor cell response to Aurora inhibition, suggesting
      that PNUTS is a potential drug target in combination anticancer
      therapy.Implications: Delineation of how PNUTS governs the mitotic activation and
      function of Aurora kinases will improve the understanding of the complex phospho
      regulation in mitotic progression, and suggest new options to enhance the
      therapeutic efficacy of Aurora inhibitors. Mol Cancer Res; 1-10. (c)2018 AACR.

PMID- 30190436
TI  - Mechanics of diseased red blood cells in human spleen and consequences for
      hereditary blood disorders.
AB  - In red blood cell (RBC) diseases, the spleen contributes to anemia by clearing
      the damaged RBCs, but its unique ability to mechanically challenge RBCs also
      poses the risk of inducing other pathogenic effects. We have analyzed RBCs in
      hereditary spherocytosis (HS) and hereditary elliptocytosis (HE), two typical
      examples of blood disorders that result in membrane protein defects in RBCs. We
      use a two-component protein-scale RBC model to simulate the traversal of the
      interendothelial slit (IES) in the human spleen, a stringent biomechanical
      challenge on healthy and diseased RBCs that cannot be directly observed in vivo.
      In HS, our results confirm that the RBC loses surface due to weakened cohesion
      between the lipid bilayer and the cytoskeleton and reveal that surface loss may
      result from vesiculation of the RBC as it crosses IES. In HE, traversing IES
      induces sustained elongation of the RBC with impaired elasticity and
      fragmentation in severe disease. Our simulations thus suggest that in inherited
      RBC disorders, the spleen not only filters out pathological RBCs but also
      directly contributes to RBC alterations. These results provide a mechanistic
      rationale for different clinical outcomes documented following splenectomy in HS
      patients with spectrin-deficient and ankyrin-deficient RBCs and offer insights
      into the pathogenic role of human spleen in RBC diseases.

PMID- 30190439
TI  - Sexual orientation and sex differences in socioeconomic status: a population
      based investigation in the National Longitudinal Study of Adolescent to Adult
      Health.
AB  - BACKGROUND: Socioeconomic status (SES) is a fundamental contributor to health;
      however, limited research has examined sexual orientation differences in SES.
      METHODS: 2008-2009 data from 14 051 participants (ages 24-32 years) in the US
      based, representative, National Longitudinal Study of Adolescent to Adult Health
      were analysed using multivariable regressions that adjusted for age, race
      ethnicity, childhood SES, urbanicity and Census region, separately for females
      and males. Modification by racial minority status (black or Latino vs white, non
      Hispanic) was also explored. RESULTS: Among females, sexual minorities (SM)
      (10.5% of females) were less likely to graduate college, and were more likely to
      be unemployed, poor/near poor, to receive public assistance and to report
      economic hardship and lower social status than heterosexuals. Adjusting for
      education attenuated many of these differences. Among males, SM (4.2% of males)
      were more likely than heterosexuals to be college graduates; however, they also
      had lower personal incomes. Lower rates of homeownership were observed among SM,
      particularly racial minority SM females. For males, household poverty patterns
      differed by race-ethnicity: among racial minority males, SM were more likely than
      heterosexuals to be living at >400% federal poverty level), whereas the pattern
      was reversed among whites. CONCLUSIONS: Sexual minorities, especially females,
      are of lower SES than their heterosexual counterparts. SES should be considered a
      potential mediator of SM stigma on health. Studies of public policies that may
      produce, as well as mitigate, observed SES inequities, are warranted.

PMID- 30190440
TI  - Marginal mandibular nerve injury during neck dissection of level IIa, and the
      influence of different types of dissection: diathermy versus cold knife.
AB  - INTRODUCTION: Post-operative injury of the marginal mandibular branch of the
      facial nerve is consider a complication in neck dissection and can be related to
      different factors including traction, devascularisation or the conduction block
      due to diathermy. MATERIAL AND METHODS: Prospective, crossover study including
      patients treated bilateral selective neck dissection of level IIa during a 12
      months-period, was performed to evaluate the efficacy of the Hayes-Martin
      manoeuvre to prevent nerve injury during the use of cold or monopolar diathermy
      dissection. RESULTS: 20 patients met the inclusion criteria (40 neck
      dissections). Just one case of a right temporal MMN weakness in the post
      operative period was observed (1/40 = 2,5%). There were no cases of permanent
      marginal mandibular nerve weakness using the Hayes-Martin manoeuvre Conclusion:
      The Hayes-Martin manoeuvre is a safe way to preserve MMN during neck dissection
      of level IIa, regardless of the type of dissection.

PMID- 30190441
TI  - Surgical treatment results of parapharyngeal space tumors: a report of 22 cases.
AB  - INTRODUCTION: Parapharyngeal space (PPS) is the anatomical area lateral to the
      upper pharynx and clinically important due to PPS tumors. They account for less
      than 1% of head and neck neoplasms. Both benign and malignant neoplasms may arise
      there and typical for this localization is diversity of histological origin.
      Complete surgical excision is still the basis of treatment. AIM OF THE STUDY:
      Evaluation of the results of surgical treatment of PPS tumors in the Department
      of Otolaryngology at the Medical University over the period 2015-2017. MATERIAL
      AND METHODS: A retrospective analysis of medical records including complaints,
      physical examination, results of imaging studies, surgical approach,
      postoperative complication and histopathological results in 22 patients with a
      diagnosis of a PPS tumors. RESULTS: The most frequent complaints reported by the
      patients were: discomfort in the throat, dysphagia, hearing disorders and a
      palpable tumor on the neck. Asymptomatic course of the disease was demonstrated
      in 4 cases. All patients were treated surgically: 2 with transoral approach, 9
      with transparotid-transcervical approach, 11 with transcervical approach. In most
      cases the tumor was removed radically. In 2 patients intracapsular tumor
      resection was performed. Based on histopathological examination the benign
      lesions dominated (18/22). In 4 cases malignant neoplasms were diagnosed:
      carcinoma ex pleomorphic adenoma, adenoid cystic carcinoma and two cases of
      squamous cell carcinoma. The most common origin of PPS tumors was deep lobe of
      parotid gland and for this group 11 patients had diagnosis of pleomorphic
      adenoma. Other diagnosis included: paraganglioma, neurofibroma, hemangioma,
      lymphangioma and rhabdomyoma. Postoperative complications occurred in 9 patients
      and presented as hoarseness and dysphagia due to paresis of the lower group of
      cranial nerves (IX, X, XII). Significant intraoperative bleeding during surgery
      occurred in 2 cases and ligation of the external carotid artery was necessary.
      CONCLUSION: Due to the anatomical topography of PPS and its content with the
      essential vessels and the lower group of cranial nerves, the surgical treatment
      of pathology of this area is still a challenge for head and neck surgeons. The
      decrease of voice quality and impaired speech and swallowing should always be
      considered as complications post the surgical resection in PPS.

PMID- 30190442
TI  - Outcomes of bevacizumab and cidofovir treatment in HPV-associated recurrent
      respiratory papillomatosis - review of the literature.
AB  - OBJECTIVE: Recurrent respiratory papillomatosis (RRP) is caused by human
      papilloma virus types 6 and 11 and occurs in both children and adults. It is
      characterized by the proliferation of benign squamous papillomas within the
      aerodigestive tract. The problem with recurrent respiratory papillomatosis
      treatment is the high recurrence of papilloma growth after surgical removal.
      METHOD: A literature review was carried out through surveys based on electronic
      data in public domains: MedLine (USA National Library of Medicine), PubMed and
      SciELO, using the keywords recurrent respiratory papillomatosis, adjuvant
      treatment, cidofovir, and bevacizumab. All types of papers written in English
      were included (cross-sectional, prospective and retrospective clinical trials,
      review papers, and case reports). RESULTS: In the recent literature, several
      types of treatment such as surgery with mechanical debulking or laser and
      adjuvant therapies are mentioned. Intralesional bevacizumab and cidofovir
      treatment may increase the interval between surgical procedures and decrease the
      number of procedures per year. CONCLUSIONS: There is still an ongoing discussion
      within the European Laryngological Society regarding the balance between
      effectiveness and side effects of RRP adjuvant treatment, but recent results show
      promising long-term effects. Bevacizumab and cidofovir in aggressive RRP give
      hope for improved treatment outcomes.

PMID- 30190444
TI  - Psychogenic voice disorders.
AB  - INTRODUCTION: Voice express the psyche and personality of a person. Psychogenic
      dysphonia is called Phononeurosis. Neurosis, depression or family, occupational
      and social conflicts are the cause of voice disturbances. The most frequent type
      of dysphonia is hyperfunctional dysphonia, rarer - hypofunctional type. AIM: The
      aim of this study is an analysis of voice quality and diagnosis of clinical type
      of psychogenic dysphonia. MATERIAL AND METHODS: The analyzed group consisted of
      50 patients with voice disorders treated in 2017 and the control group - 30
      people with physiological voice. In the diagnosed group 60% of patients were
      treated for neurosis, 12% due to depression, the others reported conflict
      situations. In the diagnosis of clinical type of psychogenic dysphonia GRBAS
      scale was used, maximum phonation time (MPT) and type of breathing were assessed.
      The visualisation of the larynx was performed using High Speed Digital Imaging
      (HSDI) technique. The parametric acoustic evaluation of voice was conducted.
      RESULTS: The most often clinical type of psychogenic dysphonia was
      hyperfunctional dysphonia, rarer hypofunctional type and vestibular voice.
      Dysphonia occurred the most often in women during the highest professional
      activity period. In the diagnosis of clinical type HSDI technique was especially
      useful allowing to visualization of the real vocal fold vibration and objective
      differentiation of hyper- and hypofunctional dysphonia. The acoustic analysis of
      the voice objectively confirmed the presence non-harmonic components - noise
      generated in the glottis in hypofunctional dysphonia. Disturbances in the way and
      breathing type caused irregularities in respiratory-phonic and articulation
      coordination.

PMID- 30190443
TI  - Obstructive sleep apnea in patients scheduled for endarterectomy - preliminary
      study.
AB  - Introduction The association between obstructive sleep apnea and atherosclerosis
      is confirmed for long time, but the pathomechanism is still not known. The aim of
      this study was to investigate the prevalence of OSA in patients scheduled for
      endarterectomy and the influence of this procedure on the sleep study parameters
      and sleepiness. Materials and methods 46 patients scheduled for open carotid
      endarterectomy were enrolled in the study. Sleep study and Epworth Sleepiness
      Scale (ESS) was performed preoperatively. In 11 out of 46 patients, sleep study
      was performed both before and after the surgery. Results The mean age of the
      group was 69,9 years (+/- 8,6), 21 patients (45,7%) were female. For 46 patients
      mean pAHI, ODI, pRDI and %snoring were 16,2 (+/- SD=15,2), 10,4 (+/- SD=12,2) and
      18,9 (+/- SD=14,9), respectively. Normal pAHI was noticed in 14 patients (30%),
      while mild (pAHI 5-15), moderate (pAHI 15-30) and severe (pAHI>30) OSA was
      observed in 13 (38%), 11 (24%) and 8 (18%) subjects, respectively. The mean ESS
      score for 27 out of 46 patients was 6,3 (+/- SD=5,6). The postoperative results
      of sleep study in 11 patients showed no significant change. Conclusions This
      study revealed the prevalence of moderate to severe OSA in 42% of patients
      scheduled for endarterectomy, while no excessive daytime sleepiness was observed
      in this group. The results of the study show that patients with carotid
      atherosclerosis should undergo sleep diagnosis in order to rule out obstructive
      sleep apnea.

PMID- 30190445
TI  - Fungal sinusitis among patients with chronic rhinosinusitis who underwent
      endoscopic sinus surgery.
AB  - INTRODUCTION: Fungal paranasal sinusitis can be either invasive or non-invasive.
      Saprophytic infections, fungus balls (FB) and allergic fungal rhinosinusitis are
      non-invasive (AFR). MATERIALS AND METHODS: The present study examined 521
      patients who underwent endoscopic sinus surgery between January 2016 and April
      2017 due to chronic paranasal sinusitis at the Department of Laryngology and
      Laryngological Oncology of the Upper Silesian Medical Centre in Katowice. The aim
      of the study was to analyse the histopathological and microbiological material
      collected intraoperatively and to determine the incidence and type of fungal
      infections among patients treated for chronic sinusitis. RESULTS: Chronic fungal
      sinusitis was confirmed in 10 of 521 operated patients. The study group consisted
      of 9 females and 1 male. Histopathological examination revealed dead mycelium in
      5 patients and colonies of Aspergillus spp. in 4, while microbiological
      examination revealed Candida albicans infection in 1 case. Allergy to inhalant
      allergens of fungal spores of Alternaria and Penicillinum was confirmed in a 73
      year-old patient, which, based on the whole clinical presentation, enabled to
      diagnose chronic allergic fungal sinusitis. The most common location of mycelium
      was the maxillary sinus, followed by the sphenoid sinus. DISCUSSION: The most
      common form of non-invasive fungal sinusitis is the so-called fungus ball, which
      was also confirmed in our report (95% of the test subjects). AFRS is more likely
      to occur in warm, moist climates that favour the growth of fungi.

PMID- 30190447
TI  - Association between Pri-miR-34b/c rs4938723 polymorphism and bladder cancer risk.
AB  - Several studies examined the impact of miR-34b/c rs4938723 polymorphism and
      cancer risk, but the findings are inconsistent. However, no study has been
      conducted to inspect the impact of miR-34b/c polymorphism on bladder cancer. This
      study aimed to assess possible association between rs4938723 polymorphism and
      bladder cancer risk. This case-control study was done on 136 pathologically
      proven bladder cancer patients and 144 controls. Genotyping of Pri-miR-34b/c
      rs4938723 polymorphism was achieved by using the polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) method. Our findings did not
      show any statistically significant differences in genotype and allele frequencies
      between bladder cancer and controls. Larger sample sizes with diverse ethnicities
      are required to validate our findings.

PMID- 30190446
TI  - Optical and thermal simulations for the design of optodes for minimally invasive
      optogenetics stimulation or photomodulation of deep and large cortical areas in
      non-human primate brain.
AB  - : The use of optogenetics or photobiomodulation in non-human primate (NHP)
      requires the ability to noninvasively stimulate large and deep cortical brain
      tissues volumes. In this context, the optical and geometrical parameters of
      optodes are critical. Methods and general guidelines to optimize these parameters
      have to be defined. OBJECTIVE: We propose the design of an optode for safe and
      efficient optical stimulation of a large volume of NHP cortex, down to 3-5 mm
      depths without inserting fibers into the cortex. APPROACH: Monte Carlo
      simulations of optical and thermal transport have been carried out using the
      Geant4 application for tomographic emission (GATE) platform. Parameters such as
      the fiber diameter, numerical aperture, number of fibers and their geometrical
      arrangement have been studied. Optimal hardware parameters are proposed to obtain
      homogeneous fluence above the fluence threshold for opsin activation without
      detrimental thermal effects. MAIN RESULTS: The simulations show that a large
      fiber diameter and a large numerical aperture are preferable since they allow
      limiting power concentration and hence the resulting thermal increases at the
      brain surface. To obtain a volume of 200-500 mm3 of brain tissues receiving a
      fluence above the opsin activation threshold for optogenetics or below a
      phototocixity threshold for photobiomodulation, a 4 fibers configuration is
      proposed. The optimal distance between the fibers was found to be 4 mm. A
      practical implementation of the optode has been performed and the corresponding
      fluence and thermal maps have been simulated. SIGNIFICANCE: The present study
      defines a method to optimize the design of optode and the choice of stimulation
      parameters for optogenetics and more generally light delivery to deep and large
      volumes of tissues in NHP brain with a controlled irradiance dosimetry. The
      general guidelines are the use of silica fibers with a large numerical aperture
      and a large diameter. The combination of several fibers is required if large
      volumes need to be stimulated while avoiding thermal effects.

PMID- 30190448
TI  - Prostate cancer tends to metastasize in the bone-mimicking microenvironment via
      activating NF-kappaB signaling.
AB  - Prostate cancer preferentially metastasizes to the bone. However, the underlying
      molecular mechanisms are still unclear. To explore the effects of a bone
      mimicking microenvironment on PC3 prostate cancer cell growth and metastasis, we
      used osteoblast differentiation medium (ODM; minimal essential medium alpha
      supplemented with L-ascorbic acid) to mimic the bone microenvironment. PC3 cells
      grown in ODM underwent epithelial-mesenchymal transition and showed enhanced
      colony formation, migration, and invasion abilities compared to the cells grown
      in normal medium. PC3 cells grown in ODM showed enhanced metastasis when injected
      in mice. A screening of signaling pathways related to invasion and metastasis
      revealed that the NF-kappaB pathway was activated, which could be reversed by Bay
      11-7082, a NF-kappaB pathway inhibitor. These results indicate that the cells in
      different culture conditions manifested significantly different biological
      behaviors and the NF-kappaB pathway is a potential therapeutic target for
      prostate cancer bone metastasis.

PMID- 30190449
TI  - Effect of Immunosuppressive Therapy on the Occurrence of Atypical Hemolytic
      Uremic Syndrome in Renal Transplant Recipients.
AB  - BACKGROUND Atypical hemolytic uremic syndrome (aHUS), a rare thrombotic
      microangiopathy, is characterized by hemolytic anemia, thrombocytopenia, and
      acute renal failure. Caused by genetic mutations in the alternative complement
      cascade, aHUS often will culminate in end-stage renal disease and occasionally
      death. Renal transplantation in aHUS patients has been contraindicated in the
      past due to the recurrence risk, with certain immunosuppressive regimens being
      commonly attributed. In this study, we analyzed the association between aHUS and
      immunosuppressive agents so as to offer evidence for the use of certain
      immunosuppressive regimens in renal transplant recipients. MATERIAL AND METHODS
      Our study is a retrospective analysis using data from the United States Renal
      Data System from 2004 to 2012. A cohort of renal transplantation patients
      diagnosed with aHUS were identified to include in the study. The primary endpoint
      was the determination of aHUS incidence in renal transplant recipients due to
      various immunosuppressive agents. The secondary endpoints were to check the
      relationship between the drug type as well as the demographic variables that
      increase the risk for aHUS. RESULTS It was found that there was a higher usage of
      sirolimus (P=0.015) and corticosteroids (P=0.030) in the aHUS patients compared
      to patients in other diagnoses group. CONCLUSIONS There was a higher usage of
      sirolimus and corticosteroids in renal transplantation patients diagnosed with
      aHUS. Unfortunately, due to the rarity of this disease, the sample size was small
      (n=14). Despite the small sample size, this data analysis throws light on the
      relationship between aHUS and immunosuppressive agents in renal transplant
      recipients, although we still have much to learn.

PMID- 30190450
TI  - Effect of Combined Use of Astragaloside IV (AsIV) and Atorvastatin (AV) on
      Expression of PPAR-gamma and Inflammation-Associated Cytokines in Atherosclerosis
      Rats.
AB  - BACKGROUND The aim of this study was to assess the effect of combined use of
      Astragaloside IV(AsIV) and atorvastatin (AV) on the expression of PPAR-gamma and
      inflammation-associated cytokines in atherosclerosis rats. MATERIAL AND METHODS
      High-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), and low
      density lipoprotein cholesterol (LDL-C) in plasma were detected through automatic
      biochemical analyzer and the histopathological analysis was performed via HE
      staining. The levels of oxidized low-density lipoprotein (oxLDL) and tumor
      necrosis factor-alpha (TNF-alpha), and interleukins (IL)-6 and IL-18 in serum
      were detected by ELISA. The expressions of proliferator-activated receptor-gamma
      (PPAR-gamma), cluster of differentiation 36 (CD36), matrix metalloprotein-9 (MMP
      9), intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion
      molecule-1(VCAM-1), and p38 and P-p38 levels were detected by Western blot. RT
      PCR was used to detect the mRNA expressions of nuclear factor-kappaB (NF-kappaB),
      PPAR-gamma, CD36, MMP-9, ICAM-1, and VCAM-1. RESULTS Administration of AsIV and
      AV significantly decreased the lipid content and oxLDL in plasma. The levels of
      TNF-alpha, IL-6, and IL-18 were significantly decreased in AsIV, AV, and AsIV +
      AV groups, especially in the AsIV + AV group. Administration decreased the levels
      of NF-kappaB, CD36, MMP-9, ICAM-1, VCAM-1, and P-p38 expression and increased the
      expression of peroxisome PPAR-gamma. Compared with the NC group, the
      atherosclerotic lesions significantly increased in the HD group, while the
      combined administration significantly inhibited the development of
      atherosclerotic disease. CONCLUSIONS Combined administration of AV and AsIV
      showed potent effects against atherosclerosis through the NF-kappaB/PPARgamma
      pathway, which may be a new therapy for treatment of atherosclerosis in the
      future.

PMID- 30190451
TI  - An Unusual Presentation of Granulomatosis with Polyangiitis (GPA).
AB  - BACKGROUND This is a very interesting case of Granulomatosis with Polyangiitis
      (GPA) presenting with hand ischemia which rapidly evolved into dry gangrene from
      the involvement of digital arteries. GPA usually affects the small and medium
      sized blood vessels. GPA affecting muscular artery causing limb ischemia is a
      rare manifestation. CASE REPORT A 72 years old Caucasian female was sent to our
      hospital for the evaluation of left hand pain and bluish discoloration, which she
      noticed for few days. Physical examination was notable for bluish discoloration
      of left 2nd to 5th fingers, which later evolved, into dry gangrene at the tips.
      Angiogram revealed ischemia with no evidence of thrombosis. Administration of
      intra-arterial nitroglycerin resulted in improved blood flow through the radial
      artery. Labs revealed ESR of 142 mm/hr. C-ANCA titer was 5120, (normal <20) and
      antiproteinase 3 was 1117 (normal <20) consistent with GPA. CONCLUSIONS GPA
      usually affects the small and medium sized blood vessels. This case highlights an
      unusual presentation of GPA manifesting as critical limb ischemia. Given the
      rarity of this circumstance, a high index of suspicion is necessary in order to
      initiate proper treatment and limb salvaging intervention.

PMID- 30190452
TI  - Body composition during early infancy and its relation with body composition at 4
      years of age in Jimma, an Ethiopian prospective cohort study.
AB  - BACKGROUND/OBJECTIVES: Low and high birth weight and rapid weight gain during
      infancy are associated with childhood obesity. Associations of birth and infancy
      body composition (BC) growth with childhood BC remain unknown in low-income
      countries. We aimed to investigate the associations of fat mass (FM) and fat-free
      mass (FFM) at birth and its accretion during early infancy with FM and FFM at the
      age of 4 years. METHODS: In the infant Anthropometry and Body Composition (iABC)
      cohort, BC was assessed at six consecutive time points from birth to 6 months and
      at 4 years of age by air displacement plethysmography. Multiple linear regression
      models were used to determine the association between FM and FFM at birth and
      their accretion rates during infancy and FM index (FMI) and FFM index (FFMI) at 4
      years in 314 children. RESULTS: One kilogram higher FFM at birth was associated
      with a 1.07 kg/m2 higher FFMI (95% CI 0.60, 1.55) at 4 years while a one SD
      increment in FFM accretion rate from 0 to 6 months was associated with a 0.24
      kg/m2 increment in FFMI (95% CI 0.11, 0.36) and with a 0.20 kg/m2 higher FMI at 4
      years (beta = 0.20; 95% CI 0.04, 0.37). FFM at birth did not predict FMI at 4
      years. FM at birth was associated with 1.17 kg/m2 higher FMI at 4 years (95% CI
      0.13, 2.22) whereas FM accretion from 0 to 4 months was associated with an
      increase in FMI of 0.30 kg/m2 (95% CI 0.12, 0.47). FM at birth did not predict
      FFMI at 4 years, and neither did FM accretion from 0 to 4 months. CONCLUSIONS: A
      higher FFM in early infancy predicted higher FFMI at 4 years while a higher FM
      accretion during early infancy predicted higher FMI at 4 years. Follow-up studies
      are merited to explore associations of childhood BC with cardio-metabolic risk
      later in life.

PMID- 30190453
TI  - Survival after blinatumomab treatment in pediatric patients with
      relapsed/refractory B-cell precursor acute lymphoblastic leukemia.

PMID- 30190454
TI  - Lenalidomide and dexamethasone in patients with relapsed multiple myeloma and
      impaired renal function: PrE1003, a PrECOG study.
AB  - Renal insufficiency is common in patients with relapsed multiple myeloma and can
      often limit choice of therapy. Lenalidomide, a critical agent in the treatment of
      relapsed multiple myeloma, is renally cleared., This phase I/II trial evaluated
      the efficacy and safety of lenalidomide with dexamethasone in patients with
      relapsed multiple myeloma and renal insufficiency. Three groups were treated,
      with creatinine clearance 30-60 cc/hr (group A), CrCl < 30 not on dialysis (group
      B), and patients on dialysis (group C) at escalating doses of lenalidomide. A
      total of 63 patients were treated and no DLTs were observed in phase I. All three
      groups were able to escalate to full dose lenalidomide 25 mg daily 21/28 days,
      although due to reduced accrual the phase II component was not entirely completed
      for groups B and C. Adverse events were as expected, including anemia, diarrhea
      and fatigue. Ten patients experienced grade 3-4 pneumonia. Overall response rate
      was 54% across all groups. PFS was 7.5 months and OS was 19.7 months.
      Lenalidomide can be given at full dose 25 mg daily 21/28 in patients with a CrCl
      > 30, and can be given daily to those with CrCl < 30, even when on dialysis, at
      doses of at least 15 mg daily.

PMID- 30190455
TI  - MEK inhibitors induce apoptosis via FoxO3a-dependent PUMA induction in colorectal
      cancer cells.
AB  - Mutations in BRAF are common to many cancers, including CRC. The MEK inhibitors
      are being investigated in BRAF-mutant CRC. In this study, we aimed to investigate
      how MEK inhibitor suppresses growth of BRAF-mutated CRC cells as well as its
      potential mechanisms. Our findings indicated that MEK inhibitor promote PUMA
      expression via ERK/FoxO3a signaling pathway. In addition, PUMA induction is
      essential for MEK inhibitor-induced apoptosis. Moreover, PUMA induction is
      required for MEK inhibitors to induced apoptosis in combination with cisplatin,
      dabrafenib, or Gefitinib. Knockdown of PUMA suppressed the anticancer effect of
      the MEK inhibitor in vivo. Our findings indicate a novel role for PUMA as a
      regulator of the antitumor effects of MEK inhibitor, suggesting that PUMA
      induction may modulate MEK inhibitor sensitivity.

PMID- 30190456
TI  - Biomimetic coating-free surfaces for long-term entrapment of air under wetting
      liquids.
AB  - Trapping air at the solid-liquid interface is a promising strategy for reducing
      frictional drag and desalting water, although it has thus far remained
      unachievable without perfluorinated coatings. Here, we report on biomimetic
      microtextures composed of doubly reentrant cavities (DRCs) and reentrant cavities
      (RCs) that can enable even intrinsically wetting materials to entrap air for long
      periods upon immersion in liquids. Using SiO2/Si wafers as the model system, we
      demonstrate that while the air entrapped in simple cylindrical cavities immersed
      in hexadecane is lost after 0.2 s, the air entrapped in the DRCs remained intact
      even after 27 days (~106 s). To understand the factors and mechanisms underlying
      this ten-million-fold enhancement, we compared the behaviors of DRCs, RCs and
      simple cavities of circular and non-circular shapes on immersion in liquids of
      low and high vapor pressures through high-speed imaging, confocal microscopy, and
      pressure cells. Those results might advance the development of coating-free
      liquid repellent surfaces.

PMID- 30190460
TI  - Drought reduces blue-water fluxes more strongly than green-water fluxes in
      Europe.
AB  - Drought comprehensively affects different interlinked aspects of the terrestrial
      water cycle, which have so far been mostly investigated without direct
      comparison. Resolving the partitioning of water deficit during drought into blue
      water runoff and green-water evapotranspiration fluxes is critical, as anomalies
      in these fluxes threaten different associated societal sectors and ecosystems.
      Here, we analyze the propagation of drought-inducing precipitation deficits
      through soil moisture reductions to their impacts on blue and green-water fluxes
      by use of comprehensive multi-decadal data from > 400 near-natural catchments
      along a steep climate gradient across Europe. We show that soil-moisture drought
      reduces runoff stronger and faster than it reduces evapotranspiration over the
      entire continent. While runoff responds within weeks, evapotranspiration can be
      unaffected for months. Understanding these drought-impact pathways across blue
      and green-water fluxes and geospheres is essential for ensuring food and water
      security, and developing early-warning and adaptation systems in support of
      society and ecosystems.

PMID- 30190459
TI  - Biological determinants of health disparities in multiple myeloma.
AB  - Multiple myeloma is a rare plasma cell cancer, and incidence rates among patients
      of African descent are about twice those among patients of European descent.
      Rates of multiple myeloma vary among different populations, but the reasons for
      the racial disparities in multiple myeloma are largely unknown. Epidemiology has
      identified risk factors for multiple myeloma including race, advanced age,
      gender, family history, and exposure to different genetic toxins including
      radiation. Race and ancestry play a large role in predicting the risk for
      multiple myeloma, yet there exists a paucity of literature that explores the
      molecular contribution of race and ancestry to disease. In this review, we
      describe the relevant literature that describes the observed racial differences
      according to distinct tumor immunobiological and ancestral differences in
      populations.

PMID- 30190457
TI  - Apolipoprotein A-IV binds alphaIIbbeta3 integrin and inhibits thrombosis.
AB  - Platelet alphaIIbbeta3 integrin and its ligands are essential for thrombosis and
      hemostasis, and play key roles in myocardial infarction and stroke. Here we show
      that apolipoprotein A-IV (apoA-IV) can be isolated from human blood plasma using
      platelet beta3 integrin-coated beads. Binding of apoA-IV to platelets requires
      activation of alphaIIbbeta3 integrin, and the direct apoA-IV-alphaIIbbeta3
      interaction can be detected using a single-molecule Biomembrane Force Probe. We
      identify that aspartic acids 5 and 13 at the N-terminus of apoA-IV are required
      for binding to alphaIIbbeta3 integrin, which is additionally modulated by apoA-IV
      C-terminus via intra-molecular interactions. ApoA-IV inhibits platelet
      aggregation and postprandial platelet hyperactivity. Human apoA-IV plasma levels
      show a circadian rhythm that negatively correlates with platelet aggregation and
      cardiovascular events. Thus, we identify apoA-IV as a novel ligand of
      alphaIIbbeta3 integrin and an endogenous inhibitor of thrombosis, establishing a
      link between lipoprotein metabolism and cardiovascular diseases.

PMID- 30190458
TI  - Jungle Express is a versatile repressor system for tight transcriptional control.
AB  - Tightly regulated promoters are essential for numerous biological applications,
      where strong inducibility, portability, and scalability are desirable. Current
      systems are often incompatible with large-scale fermentations due to high inducer
      costs and strict media requirements. Here, we describe the bottom-up engineering
      of 'Jungle Express', an expression system that enables efficient gene regulation
      in diverse proteobacteria. This system is guided by EilR, a multidrug-binding
      repressor with high affinity to its optimized operator and cationic dyes that act
      as powerful inducers at negligible costs. In E. coli, the engineered promoters
      exhibit minimal basal transcription and are inducible over four orders of
      magnitude by 1 uM crystal violet, reaching expression levels exceeding those of
      the strongest current bacterial systems. Further, we provide molecular insights
      into specific interactions of EilR with its operator and with two inducers. The
      versatility of Jungle Express opens the way for tightly controlled and efficient
      gene expression that is not restricted to host organism, substrate, or scale.

PMID- 30190461
TI  - Cryo-EM of full-length alpha-synuclein reveals fibril polymorphs with a common
      structural kernel.
AB  - alpha-Synuclein (aSyn) fibrillar polymorphs have distinct in vitro and in vivo
      seeding activities, contributing differently to synucleinopathies. Despite
      numerous prior attempts, how polymorphic aSyn fibrils differ in atomic structure
      remains elusive. Here, we present fibril polymorphs from the full-length
      recombinant human aSyn and their seeding capacity and cytotoxicity in vitro. By
      cryo-electron microscopy helical reconstruction, we determine the structures of
      the two predominant species, a rod and a twister, both at 3.7 A resolution. Our
      atomic models reveal that both polymorphs share a kernel structure of a bent beta
      arch, but differ in their inter-protofilament interfaces. Thus, different packing
      of the same kernel structure gives rise to distinct fibril polymorphs. Analyses
      of disease-related familial mutations suggest their potential contribution to the
      pathogenesis of synucleinopathies by altering population distribution of the
      fibril polymorphs. Drug design targeting amyloid fibrils in neurodegenerative
      diseases should consider the formation and distribution of concurrent fibril
      polymorphs.

PMID- 30190463
TI  - Printing two-dimensional gallium phosphate out of liquid metal.
AB  - Two-dimensional piezotronics will benefit from the emergence of new crystals
      featuring high piezoelectric coefficients. Gallium phosphate (GaPO4) is an
      archetypal piezoelectric material, which does not naturally crystallise in a
      stratified structure and hence cannot be exfoliated using conventional methods.
      Here, we report a low-temperature liquid metal-based two-dimensional printing and
      synthesis strategy to achieve this goal. We exfoliate and surface print the
      interfacial oxide layer of liquid gallium, followed by a vapour phase reaction.
      The method offers access to large-area, wide bandgap two-dimensional (2D) GaPO4
      nanosheets of unit cell thickness, while featuring lateral dimensions reaching
      centimetres. The unit cell thick nanosheets present a large effective out-of
      plane piezoelectric coefficient of 7.5 +/- 0.8 pm V-1. The developed printing
      process is also suitable for the synthesis of free standing GaPO4 nanosheets. The
      low temperature synthesis method is compatible with a variety of electronic
      device fabrication procedures, providing a route for the development of future 2D
      piezoelectric materials.

PMID- 30190465
TI  - Wilson disease.

PMID- 30190462
TI  - Co-activation of super-enhancer-driven CCAT1 by TP63 and SOX2 promotes squamous
      cancer progression.
AB  - Squamous cell carcinomas (SCCs) are aggressive malignancies. Previous report
      demonstrated that master transcription factors (TFs) TP63 and SOX2 exhibited
      overlapping genomic occupancy in SCCs. However, functional consequence of their
      frequent co-localization at super-enhancers remains incompletely understood.
      Here, epigenomic profilings of different types of SCCs reveal that TP63 and SOX2
      cooperatively and lineage-specifically regulate long non-coding RNA (lncRNA)
      CCAT1 expression, through activation of its super-enhancers and promoter.
      Silencing of CCAT1 substantially reduces cellular growth both in vitro and in
      vivo, phenotyping the effect of inhibiting either TP63 or SOX2. ChIRP analysis
      shows that CCAT1 forms a complex with TP63 and SOX2, which regulates EGFR
      expression by binding to the super-enhancers of EGFR, thereby activating both
      MEK/ERK1/2 and PI3K/AKT signaling pathways. These results together identify a SCC
      specific DNA/RNA/protein complex which activates TP63/SOX2-CCAT1-EGFR cascade and
      promotes SCC tumorigenesis, advancing our understanding of transcription
      dysregulation in cancer biology mediated by master TFs and super-enhancers.

PMID- 30190466
TI  - Reflection of near-infrared light confers thermal protection in birds.
AB  - Biologists have focused their attention on the optical functions of light
      reflected at ultraviolet and human-visible wavelengths. However, most radiant
      energy in sunlight occurs in 'unseen' near-infrared (NIR) wavelengths. The
      capacity to reflect solar radiation at NIR wavelengths may enable animals to
      control heat gain and remain within their critical thermal limits. Here, using a
      continent-wide phylogenetic analysis of Australian birds, we show that species
      occupying hot, arid environments reflect more radiant energy in NIR wavelengths
      than species in thermally benign environments, even when controlling for
      variation in visible colour. Biophysical models confirm that smaller species gain
      a greater advantage from high NIR reflectivity in hot, arid environments,
      reducing water loss from compensatory evaporative cooling by up to 2% body mass
      per hour. These results highlight the importance of NIR reflectivity for thermal
      protection, which may become increasingly critical as the frequency of extreme
      climatic events increases.

PMID- 30190468
TI  - Development of a novel target module redirecting UniCAR T cells to Sialyl Tn
      expressing tumor cells.

PMID- 30190467
TI  - GATA2 zinc finger 1 mutations are associated with distinct clinico-biological
      features and outcomes different from GATA2 zinc finger 2 mutations in adult acute
      myeloid leukemia.
AB  - Mutations of the GATA binding protein 2 (GATA2) gene in myeloid malignancies
      usually cluster in the zinc finger 1 (ZF1) and the ZF2 domains. Mutations in
      different locations of GATA2 may have distinct impact on clinico-biological
      features and outcomes in AML patients, but little is known in this aspect. In
      this study, we explored GATA2 mutations in 693 de novo non-M3 AML patients and
      identified 44 GATA2 mutations in 43 (6.2%) patients, including 31 in ZF1, 10 in
      ZF2, and three outside the two domains. Different from GATA2 ZF2 mutations, ZF1
      mutations were closely associated with French-American-British (FAB) M1 subtype,
      CEBPA double mutations (CEBPAdouble-mut), but inversely correlated with FAB M4
      subtype, NPM1 mutations, and FLT3-ITD. ZF1-mutated AML patients had a
      significantly longer overall survival (OS) than GATA2-wild patients and ZF2
      mutated patients in total cohort as well as in those with intermediate-risk
      cytogenetics and normal karyotype. ZF1 mutations also predicted better disease
      free survival and a trend of better OS in CEBPAdouble-mut patients. Sequential
      analysis showed GATA2 mutations could be acquired at relapse. In conclusion,
      GATA2 ZF1 mutations are associated with distinct clinico-biological features and
      predict better prognosis, different from ZF2 mutations, in AML patients.

PMID- 30190464
TI  - LincRNA H19 protects from dietary obesity by constraining expression of
      monoallelic genes in brown fat.
AB  - Increasing brown adipose tissue (BAT) thermogenesis in mice and humans improves
      metabolic health and understanding BAT function is of interest for novel
      approaches to counteract obesity. The role of long noncoding RNAs (lncRNAs) in
      these processes remains elusive. We observed maternally expressed, imprinted
      lncRNA H19 increased upon cold-activation and decreased in obesity in BAT.
      Inverse correlations of H19 with BMI were also observed in humans. H19
      overexpression promoted, while silencing of H19 impaired adipogenesis, oxidative
      metabolism and mitochondrial respiration in brown but not white adipocytes. In
      vivo, H19 overexpression protected against DIO, improved insulin sensitivity and
      mitochondrial biogenesis, whereas fat H19 loss sensitized towards HFD weight
      gains. Strikingly, paternally expressed genes (PEG) were largely absent from BAT
      and we demonstrated that H19 recruits PEG-inactivating H19-MBD1 complexes and
      acts as BAT-selective PEG gatekeeper. This has implications for our understanding
      how monoallelic gene expression affects metabolism in rodents and, potentially,
      humans.

PMID- 30190469
TI  - Long-term efficacy and safety of dasatinib in patients with chronic myeloid
      leukemia in accelerated phase who are resistant to or intolerant of imatinib.

PMID- 30190471
TI  - Water chemistry reveals a significant decline in coral calcification rates in the
      southern Red Sea.
AB  - Experimental and field evidence support the assumption that global warming and
      ocean acidification is decreasing rates of calcification in the oceans. Local
      measurements of coral growth rates in reefs from various locations have suggested
      a decline of ~6-10% per decade since the late 1990's. Here, by measuring open
      water strontium-to-alkalinity ratios along the Red Sea, we show that the net
      contribution of hermatypic corals to the CaCO3 budget of the southern and central
      Red Sea declined by ~100% between 1998 and 2015 and remained low between 2015 and
      2018. Measured differences in total alkalinity of the Red Sea surface water
      indicate a 26 +/- 16% decline in total CaCO3 deposition rates along the basin.
      These findings suggest that coral reefs of the southern Red Sea are under severe
      stress and demonstrate the strength of geochemical measurements as cost-effective
      indicators for calcification trends on regional scales.

PMID- 30190470
TI  - Structure of the human plasma membrane Ca2+-ATPase 1 in complex with its
      obligatory subunit neuroplastin.
AB  - Plasma membrane Ca2+-ATPases (PMCAs) are key regulators of global Ca2+
      homeostasis and local intracellular Ca2+ dynamics. Recently, Neuroplastin (NPTN)
      and basigin were identified as previously unrecognized obligatory subunits of
      PMCAs that dramatically increase the efficiency of PMCA-mediated Ca2+ clearance.
      Here, we report the cryo-EM structure of human PMCA1 (hPMCA1) in complex with
      NPTN at a resolution of 4.1 A for the overall structure and 3.9 A for the
      transmembrane domain. The single transmembrane helix of NPTN interacts with the
      TM8-9-linker and TM10 of hPMCA1. The subunits are required for the hPMCA1
      functional activity. The NPTN-bound hPMCA1 closely resembles the E1-Mg2+
      structure of endo(sarco)plasmic reticulum Ca2+ ATPase and the Ca2+ site is
      exposed through a large open cytoplasmic pathway. This structure provides insight
      into how the subunits bind to the PMCAs and serves as an important basis for
      understanding the functional mechanisms of this essential calcium pump family.

PMID- 30190474
TI  - Fumarate hydratase loss promotes mitotic entry in the presence of DNA damage
      after ionising radiation.
AB  - An altered response to DNA damage is commonly associated with genomic
      instability, a hallmark of cancer. Fumarate hydratase (FH) was recently
      characterised as a DNA repair factor required in non-homologous end-joining
      (NHEJ) through the local production of fumarate. Inactivating germline mutations
      in FH cause hereditary leiomyomatosis and renal cell cancer (HLRCC), a cancer
      syndrome characterised by accumulation of fumarate. Recent data indicate that, in
      FH-deficient cells, fumarate suppresses homologous recombination DNA repair upon
      DNA double-strand breaks, compromising genome integrity. Here, we show that FH
      loss confers resistance to DNA damage caused by ionising radiation (IR), and
      promotes early mitotic entry after IR in a fumarate-specific manner, even in the
      presence of unrepaired damage, by suppressing checkpoint maintenance. We also
      showed that higher levels of DNA damage foci are detectable in untreated FH
      deficient cells. Overall, these data indicate that FH loss and fumarate
      accumulation lead to a weakened G2 checkpoint that predisposes to endogenous DNA
      damage and confers resistance to IR.

PMID- 30190473
TI  - Reduced expression of stearoyl-CoA desaturase-1, but not free fatty acid receptor
      2 or 4 in subcutaneous adipose tissue of patients with newly diagnosed type 2
      diabetes mellitus.
AB  - BACKGROUND: In subcutaneous adipose tissue (SAT), higher stearoyl-CoA desaturase
      1 (SCD1) expression has been related to improved insulin sensitivity in
      thiazolidinedione-treated type 2 diabetes mellitus patients. In animal models,
      deficiency of the free fatty acid receptor (FFAR) 2 associated with higher and
      FFAR4-deficiency with lower insulin sensitivity. We hypothesized that increased
      FFAR2 expression and reductions in FFAR4 and SCD1 expression in SAT of type 2
      diabetes mellitus patients associate positively with insulin resistance and
      impaired beta cell function. METHODS: Twenty-five type 2 diabetes mellitus
      patients and 25 glucose-tolerant humans (CON) matched for sex, age, and BMI
      underwent mixed-meal tests to assess insulin sensitivity (OGIS) and beta cell
      function (DeltaAUC(C-peptide)0-180 min/DeltaAUC(glucose)0-180 min) in a cross
      sectional study. Gene and protein expression of SCD1 and FFAR2/4 were quantified
      in SAT biopsies. RESULTS: Insulin sensitivity was 14% and beta cell function 71%
      (both p < 0.001) lower in type 2 diabetes mellitus patients. In type 2 diabetes
      mellitus, SCD1 mRNA was fivefold (p < 0.001) and protein expression twofold (p <
      0.01) lower. While FFAR2/4 mRNA and protein expression did not differ between
      groups, FFAR2 protein levels correlated negatively with beta cell function only
      in CON (r = -0.74, p < 0.01). However, neither SCD1 nor FFAR2/4 protein
      expression correlated with insulin sensitivity in both groups. CONCLUSIONS: Type
      2 diabetes patients have lower SCD1, which does not associate with insulin
      resistance. Only in non-diabetic humans, FFAR2 associated with impaired beta cell
      function.

PMID- 30190476
TI  - Publisher Correction: Collective molecular switching in hybrid superlattices for
      light-modulated two-dimensional electronics.
AB  - The original version of this article incorrectly listed an affiliation of Sara
      Bonacchi as 'Present address: Institut National de la Recherche Scientifique
      (INRS), EMT Center, Boulevard Lionel-Boulet, Varennes, QC, J3X 1S2, 1650,
      Canada', instead of the correct 'Present address: Department of Chemical Sciences
      - University of Padua - Via Francesco Marzolo 1 - 35131 Padova - Italy'. And an
      affiliation of Emanuele Orgiu was incorrectly listed as 'Present address:
      Department of Chemical Sciences, University of Padua, Via Francesco Marzolo 1,
      Padova, 35131, Italy', instead of the correct 'Present address: Institut National
      de la Recherche Scientifique (INRS), EMT Center, Boulevard Lionel-Boulet,
      Varennes, QC, J3X 1S2, 1650, Canada'. This has been corrected in both the PDF and
      HTML versions of the article.

PMID- 30190472
TI  - The biological significance of histone modifiers in multiple myeloma: clinical
      applications.
AB  - Multiple myeloma (MM) is a clonal plasma cell disorder that is characterized by a
      variety of genetic alterations. Recent studies have highlighted not only the
      importance of these genetic events but also epigenetic aberrations including DNA
      methylation, histone modifications, and non-coding RNAs in the biology of MM.
      Post-translational modifications of histone, such as methylation and acetylation,
      contribute to chromatin dynamics, and are modulated by histone modifying enzymes,
      and dysregulation of these enzymes is implicated in the pathogenesis of cancers,
      including MM. Histone modifiers also have non-histone substrates and
      enzymatically independent roles, which are also involved in tumorigenesis. Here
      we review and provide comprehensive insight into the biologic significance of
      histone methyl- and acetyl-modifiers in MM, and further provide an overview of
      the clinical applications of histone modifier inhibitors, especially histone
      deacetylase inhibitors. These findings underline the emerging roles of histone
      modifiers in the pathogenesis of MM, and further highlight the possibility of
      novel epigenetic therapies in MM.

PMID- 30190475
TI  - Realization of vertical metal semiconductor heterostructures via solution phase
      epitaxy.
AB  - The creation of crystal phase heterostructures of transition metal chalcogenides,
      e.g., the 1T/2H heterostructures, has led to the formation of metal/semiconductor
      junctions with low potential barriers. Very differently, post-transition metal
      chalcogenides are semiconductors regardless of their phases. Herein, we report,
      based on experimental and simulation results, that alloying between 1T-SnS2 and
      1T-WS2 induces a charge redistribution in Sn and W to realize metallic
      Sn0.5W0.5S2 nanosheets. These nanosheets are epitaxially deposited on surfaces of
      semiconducting SnS2 nanoplates to form vertical heterostructures. The ohmic-like
      contact formed at the Sn0.5W0.5S2/SnS2 heterointerface affords rapid transport of
      charge carriers, and allows for the fabrication of fast photodetectors. Such
      facile charge transfer, combined with a high surface affinity for acetone
      molecules, further enables their use as highly selective 100 ppb level acetone
      sensors. Our work suggests that combining compositional and structural control in
      solution-phase epitaxy holds promises for solution-processible thin-film
      optoelectronics and sensors.

PMID- 30190477
TI  - LY6E mediates an evolutionarily conserved enhancement of virus infection by
      targeting a late entry step.
AB  - Interferons (IFNs) contribute to cell-intrinsic antiviral immunity by inducing
      hundreds of interferon-stimulated genes (ISGs). In a screen to identify antiviral
      ISGs, we unexpectedly found that LY6E, a member of the LY6/uPAR family, enhanced
      viral infection. Here, we show that viral enhancement by ectopically expressed
      LY6E extends to several cellular backgrounds and affects multiple RNA viruses.
      LY6E does not impair IFN antiviral activity or signaling, but rather promotes
      viral entry. Using influenza A virus as a model, we narrow the enhancing effect
      of LY6E to uncoating after endosomal escape. Diverse mammalian orthologs of LY6E
      also enhance viral infectivity, indicating evolutionary conservation of function.
      By structure-function analyses, we identify a single amino acid in a predicted
      loop region that is essential for viral enhancement. Our study suggests that LY6E
      belongs to a class of IFN-inducible host factors that enhance viral infectivity
      without suppressing IFN antiviral activity.

PMID- 30190478
TI  - Nucleolar fibrillarin is an evolutionarily conserved regulator of bacterial
      pathogen resistance.
AB  - Innate immunity is the first line of defense against infections. Pathways
      regulating innate responses can also modulate other processes, including stress
      resistance and longevity. Increasing evidence suggests a role for the nucleolus
      in regulating cellular processes implicated in health and disease. Here we show
      the highly conserved nucleolar protein, fibrillarin, is a vital factor regulating
      pathogen resistance. Fibrillarin knockdown enhances resistance in C. elegans
      against bacterial pathogens, higher levels of fibrillarin induce susceptibility
      to infection. Pathogenic infection reduces nucleolar size, ribsosomal RNA, and
      fibrillarin levels. Genetic epistasis reveals fibrillarin functions independently
      of the major innate immunity mediators, suggesting novel mechanisms of pathogen
      resistance. Bacterial infection also reduces nucleolar size and fibrillarin
      levels in mammalian cells. Fibrillarin knockdown prior to infection increases
      intracellular bacterial clearance, reduces inflammation, and enhances cell
      survival. Collectively, these findings reveal an evolutionarily conserved role of
      fibrillarin in infection resistance and suggest the nucleolus as a focal point in
      innate immune responses.

PMID- 30190479
TI  - Expression profile of translation initiation factor eIF2B5 in diffuse large B
      cell lymphoma and its correlation to clinical outcome.

PMID- 30190482
TI  - Reduced occupancy of hedgehogs (Erinaceus europaeus) in rural England and Wales:
      The influence of habitat and an asymmetric intra-guild predator.
AB  - Agricultural landscapes have become increasingly intensively managed resulting in
      population declines across a broad range of taxa, including insectivores such as
      the hedgehog (Erinaceus europaeus). Hedgehog declines have also been attributed
      to an increase in the abundance of badgers (Meles meles), an intra-guild
      predator. The status of hedgehogs across the rural landscape at large spatial
      scales is, however, unknown. In this study, we used footprint tracking tunnels to
      conduct the first national survey of rural hedgehog populations in England and
      Wales. Single and two-species occupancy modelling was used to quantify hedgehog
      occupancy in relation to habitat and predator covariates. Hedgehog occupancy was
      low (22% nationally), and significantly negatively related to badger sett density
      and positively related to the built environment. Hedgehogs were also absent from
      71% of sites that had no badger setts, indicating that large areas of the rural
      landscape are not occupied by hedgehogs. Our results provide the first field
      based national survey of hedgehogs, providing a robust baseline for future
      monitoring. Furthermore, the combined effects of increasing badger abundance and
      intensive agriculture may have provided a perfect storm for hedgehogs in rural
      Britain, leading to worryingly low levels of occupancy over large spatial scales.

PMID- 30190480
TI  - DISC1 regulates N-methyl-D-aspartate receptor dynamics: abnormalities induced by
      a Disc1 mutation modelling a translocation linked to major mental illness.
AB  - The neuromodulatory gene DISC1 is disrupted by a t(1;11) translocation that is
      highly penetrant for schizophrenia and affective disorders, but how this
      translocation affects DISC1 function is incompletely understood. N-methyl-D
      aspartate receptors (NMDAR) play a central role in synaptic plasticity and
      cognition, and are implicated in the pathophysiology of schizophrenia through
      genetic and functional studies. We show that the NMDAR subunit GluN2B complexes
      with DISC1-associated trafficking factor TRAK1, while DISC1 interacts with the
      GluN1 subunit and regulates dendritic NMDAR motility in cultured mouse neurons.
      Moreover, in the first mutant mouse that models DISC1 disruption by the
      translocation, the pool of NMDAR transport vesicles and surface/synaptic NMDAR
      expression are increased. Since NMDAR cell surface/synaptic expression is tightly
      regulated to ensure correct function, these changes in the mutant mouse are
      likely to affect NMDAR signalling and synaptic plasticity. Consistent with these
      observations, RNASeq analysis of the translocation carrier-derived human neurons
      indicates abnormalities of excitatory synapses and vesicle dynamics. RNASeq
      analysis of the human neurons also identifies many differentially expressed genes
      previously highlighted as putative schizophrenia and/or depression risk factors
      through large-scale genome-wide association and copy number variant studies,
      indicating that the translocation triggers common disease pathways that are
      shared with unrelated psychiatric patients. Altogether, our findings suggest that
      translocation-induced disease mechanisms are likely to be relevant to mental
      illness in general, and that such disease mechanisms include altered NMDAR
      dynamics and excitatory synapse function. This could contribute to the cognitive
      disorders displayed by translocation carriers.

PMID- 30190483
TI  - Data-driven approach for the prediction and interpretation of core-electron loss
      spectroscopy.
AB  - Spectroscopy is indispensable for determining atomic configurations, chemical
      bondings, and vibrational behaviours, which are crucial information for materials
      development. Despite their importance, the interpretation of spectra using "human
      driven" methods, such as the manual comparison of experimental spectra with
      reference/simulated spectra, is difficult due to the explosive increase in the
      number of experimental spectra to be observed. To overcome the limitations of the
      "human-driven" approach, we develop a new "data-driven" approach based on machine
      learning techniques by combining the layer clustering and decision tree methods.
      The proposed method is applied to the 46 oxygen-K edges of the ELNES/XANES
      spectra of oxide compounds. With this method, the spectra can be interpreted in
      accordance with the material information. Furthermore, we demonstrate that our
      method can predict spectral features from the material information. Our approach
      has the potential to provide information about a material that cannot be
      determined manually as well as predict a plausible spectrum from the geometric
      information alone.

PMID- 30190481
TI  - Differentiation therapy and the mechanisms that terminate cancer cell
      proliferation without harming normal cells.
AB  - Chemotherapeutic drugs have a common intent to activate apoptosis in tumor cells.
      However, master regulators of apoptosis (e.g., p53, p16/CDKN2A) are frequently
      genetically inactivated in cancers, resulting in multidrug resistance. An
      alternative, p53-independent method for terminating malignant proliferation is to
      engage terminal-differentiation. Normally, the exponential proliferation of
      lineage-committed progenitors, coordinated by the master transcription factor
      (TF) MYC, is self-limited by forward-differentiation to terminal lineage-fates.
      In cancers, however, this exponential proliferation is disengaged from terminal
      differentiation. The mechanisms underlying this decoupling are mostly unknown. We
      performed a systematic review of published literature (January 2007-June 2018) to
      identify gene pathways linked to differentiation-failure in three treatment
      recalcitrant cancers: hepatocellular carcinoma (HCC), ovarian cancer (OVC), and
      pancreatic ductal adenocarcinoma (PDAC). We analyzed key gene alterations in
      various apoptosis, proliferation and differentiation pathways to determine
      whether it is possible to predict treatment outcomes and suggest novel therapies.
      Poorly differentiated tumors were linked to poorer survival across histologies.
      Our analyses suggested loss-of-function events to master TF drivers of lineage
      fates and their cofactors as being linked to differentiation-failure: genomic
      data in TCGA and ICGC databases demonstrated frequent haploinsufficiency of
      lineage master TFs (e.g., GATA4/6) in poorly differentiated tumors; the
      coactivators that these TFs use to activate genes (e.g. ARID1A, PBRM1) were also
      frequently inactivated by genetic mutation and/or deletion. By contrast,
      corepressor components (e.g., DNMT1, EED, UHRF1, and BAZ1A/B), that oppose
      coactivators to repress or turn off genes, were frequently amplified instead, and
      the level of amplification was highest in poorly differentiated lesions. This
      selection by neoplastic evolution towards unbalanced activity of transcriptional
      corepressors suggests these enzymes as candidate targets for inhibition aiming to
      re-engage forward-differentiation. This notion is supported by both pre-clinical
      and clinical trial literature.

PMID- 30190484
TI  - Comparative metabolism of xenobiotic chemicals by cytochrome P450s in the
      nematode Caenorhabditis elegans.
AB  - We investigated the metabolic capabilities of C. elegans using compounds whose
      metabolism has been well characterised in mammalian systems. We find that similar
      metabolites are produced in C. elegans as in mammals but that C. elegans is
      deficient in CYP1-like metabolism, as has been seen in other studies. We show
      that CYP-34A9, CYP-34A10 and CYP-36A1 are the principal enzymes responsible for
      the metabolism of tolbutamide in C. elegans. These are related to the mammalian
      enzymes that metabolise this compound but are not the closest homologs suggesting
      that sequence comparison alone will not predict functional conservation among
      cytochrome P450s. In mammals, metabolite production from amytryptiline and
      dextromethorphan is dependent on specific cytochrome P450s. However, in C.
      elegans we did not find evidence of similar specificity: the same metabolites
      were produced but in small amounts by numerous cytochrome P450s. We conclude
      that, while some aspects of cytochrome P450 mediated metabolism in C. elegans are
      similar to mammals, there are differences in the production of some metabolites
      and in the underlying genetics of metabolism.

PMID- 30190485
TI  - Streptococcus mutans extracellular DNA levels depend on the number of bacteria in
      a biofilm.
AB  - Streptococcus mutans is a component of oral plaque biofilm that accumulates on
      the surface of teeth. The biofilm consists of extracellular components including
      extracellular DNA (eDNA). This study was conducted to investigate the factors
      that may affect the eDNA levels of S. mutans in biofilms. For the study, S.
      mutans UA159 biofilms were formed for 52 h on hydroxyapatite (HA) discs in 0%
      (w/v) sucrose +0% glucose, 0.5% sucrose, 1% sucrose, 0.5% glucose, 1% glucose, or
      0.5% sucrose +0.5% glucose. Acidogenicity of S. mutans in the biofilms was
      measured after biofilm formation (22 h) up to 52 h. eDNA was collected after 52 h
      biofilm formation and measured using DNA binding fluorescent dye, SYBR Green I.
      Biofilms cultured in 0.5% sucrose or glucose had more eDNA and colony forming
      units (CFUs) and less exopolysaccharides (EPSs) than the biofilms cultured in 1%
      sucrose or glucose at 52 h, respectively. The biofilms formed in 0% sucrose +0%
      glucose maintained pH around 7, while the biofilms grown in 0.5% sucrose had more
      acidogenicity than those grown in 1% sucrose, and the same pattern was shown in
      glucose. In conclusion, the results of this study show that the number of S.
      mutans in biofilms affects the concentrations of eDNA as well as the
      acidogenicity of S. mutans in the biofilms. In addition, the thickness of EPS is
      irrelevant to eDNA aggregation within biofilms.

PMID- 30190486
TI  - The diagnostic accuracy of circulating tumor DNA for the detection of EGFR-T790M
      mutation in NSCLC: a systematic review and meta-analysis.
AB  - This pooled analysis aims at evaluating the diagnostic accuracy of circulating
      tumor (ct) DNA for the detection of EGFR-T790M mutation in NSCLC patients who
      progressed after EGFR-TKIs. Data from all published studies, reporting both
      sensitivity and specificity of plasma-based EGFR-T790M mutation testing by ctDNA
      were collected by searching in PubMed, Cochrane Library, American Society of
      Clinical Oncology, European Society of Medical Oncology and World Conference of
      Lung Cancer meeting proceedings. A total of twenty-one studies, with 1639
      patients, were eligible. The pooled sensitivity of ctDNA analysis was 0.67 (95%
      CI: 0.64-0.70) and the pooled specificity was 0.80 (95% CI: 0.77-0.83). The
      pooled positive predictive value (PPV) was 0.85 (95% CI: 0.82-0.87) and the
      pooled negative predictive value (NPV) was 0.60 (95% CI: 0.56-0.63). The positive
      likelihood ratio (PLR) and negative likelihood ratio (NLR) were 2.67 (95% CI:
      1.86-3.82) and 0.46 (95% CI: 0.38-0.54), respectively. The pooled diagnostic odds
      ratio (DOR) was 7.27 (4.39-12.05) and the area under the curve (AUC) of the
      summary receiver operating characteristics (sROC) curve was 0.77. The ctDNA
      analysis represents a promising, non-invasive approach to detect and monitor the
      T790M mutation status in NSCLC patients. Development of standardized
      methodologies and clinical validation are recommended.

PMID- 30190488
TI  - Dissecting causes for improved survival among patients with acute myeloid
      leukemia in two different eras receiving identical regimens in sequential
      randomized studies.

PMID- 30190489
TI  - Wilson disease.
AB  - Wilson disease (WD) is a potentially treatable, inherited disorder of copper
      metabolism that is characterized by the pathological accumulation of copper. WD
      is caused by mutations in ATP7B, which encodes a transmembrane copper
      transporting ATPase, leading to impaired copper homeostasis and copper overload
      in the liver, brain and other organs. The clinical course of WD can vary in the
      type and severity of symptoms, but progressive liver disease is a common feature.
      Patients can also present with neurological disorders and psychiatric symptoms.
      WD is diagnosed using diagnostic algorithms that incorporate clinical symptoms
      and signs, measures of copper metabolism and DNA analysis of ATP7B. Available
      treatments include chelation therapy and zinc salts, which reverse copper
      overload by different mechanisms. Additionally, liver transplantation is
      indicated in selected cases. New agents, such as tetrathiomolybdate salts, are
      currently being investigated in clinical trials, and genetic therapies are being
      tested in animal models. With early diagnosis and treatment, the prognosis is
      good; however, an important issue is diagnosing patients before the onset of
      serious symptoms. Advances in screening for WD may therefore bring earlier
      diagnosis and improvements for patients with WD.

PMID- 30190487
TI  - A potential link between gambling addiction severity and central dopamine levels:
      Evidence from spontaneous eye blink rates.
AB  - Accumulating evidence points at similarities between substance use disorders
      (SUD) and gambling disorder on the behavioral and neural level. In SUD,
      attenuation of striatal D2/3-receptor availability is a consistent finding, at
      least for stimulating substances. For gambling disorder, no clear association
      with striatal D2/3-receptor availability has been unveiled so far. With its
      presumably negligible dopaminergic toxicity, possible differences in receptor
      availability in gambling disorder might constitute a vulnerability marker.
      Spontaneous eye blink rate (sEBR) is discussed as a potential proxy measure for
      striatal dopamine D2/3-receptor availability. Here we examined sEBR in 21 male
      problem gamblers and 20 healthy control participants. In addition, participants
      completed a screening questionnaire for overall psychopathology and self-reported
      measures of alcohol and nicotine consumption. We found no significant difference
      in sEBR between gamblers and controls. However, in gamblers, sEBR was negatively
      associated with gambling severity and positively associated with psychopathology.
      A final exploratory analysis revealed that healthy controls with low sEBR
      displayed higher alcohol and nicotine consumption than healthy participants with
      high sEBR. Although the exact association between dopamine transmission and sEBR
      is still debated, our findings reveal that sEBR is sensitive to inter-individual
      differences in gambling disorder severity in problem gamblers.

PMID- 30190490
TI  - Lysine acetylation modulates mouse sperm capacitation.
AB  - Mammalian sperm are unable to fertilize the egg immediately after ejaculation. To
      gain fertilization competence, they need to undergo a series of modifications
      inside the female reproductive tract, known as capacitation. Capacitation
      involves several molecular events such as phosphorylation cascades,
      hyperpolarization of the plasma membrane and intracellular Ca2+ changes, which
      prepare the sperm to develop two essential features for fertilization competence:
      hyperactivation and acrosome reaction. Since sperm cells lack new protein
      biosynthesis, post-translational modification of existing proteins plays a
      crucial role to obtain full functionality. Here, we show the presence of
      acetylated proteins in murine sperm, which increase during capacitation.
      Pharmacological hyperacetylation of lysine residues in non-capacitated sperm
      induces activation of PKA, hyperpolarization of the sperm plasma membrane,
      CatSper opening and Ca2+ influx, all capacitation-associated molecular events.
      Furthermore, hyperacetylation of non-capacitated sperm promotes hyperactivation
      and prepares the sperm to undergo acrosome reaction. Together, these results
      indicate that acetylation could be involved in the acquisition of fertilization
      competence of mammalian sperm.

PMID- 30190491
TI  - Intrinsic refractive index matched 3D dSTORM with two objectives: Comparison of
      detection techniques.
AB  - We have built a setup for 3D single molecule localisation microscopy (SMLM) where
      a very high resolution is achieved by, firstly, the use of two objectives instead
      of one and, secondly, minimizing optical aberrations by refractive index matching
      with a glycerol-water mixture as immersion medium in conjunction with glycerol
      immersion objectives. Multiple optical paths of the microscope allow to switch
      between astigmatic and interferometric localisation along the optical axis, thus
      enabling a direct comparison of the performance of these localisation methods.

PMID- 30190492
TI  - Estimating regional flood discharge during Palaeocene-Eocene global warming.
AB  - Among the most urgent challenges in future climate change scenarios is accurately
      predicting the magnitude to which precipitation extremes will intensify.
      Analogous changes have been reported for an episode of millennial-scale 5 
      degrees C warming, termed the Palaeocene-Eocene Thermal Maximum (PETM; 56 Ma),
      providing independent constraints on hydrological response to global warming.
      However, quantifying hydrologic extremes during geologic global warming analogs
      has proven difficult. Here we show that water discharge increased by at least
      1.35 and potentially up to 14 times during the early phase of the PETM in
      northern Spain. We base these estimates on analyses of channel dimensions,
      sediment grain size, and palaeochannel gradients across the early PETM, which is
      regionally marked by an abrupt transition from overbank palaeosol deposits to
      conglomeratic fluvial sequences. We infer that extreme floods and channel
      mobility quickly denuded surrounding soil-mantled landscapes, plausibly enhanced
      by regional vegetation decline, and exported enormous quantities of terrigenous
      material towards the ocean. These results support hypotheses that extreme
      rainfall events and associated risks of flooding increase with global warming at
      similar, but potentially at much higher, magnitudes than currently predicted.

PMID- 30190493
TI  - Oral fibropapillomatosis and epidermal hyperplasia of the lip in newborn lambs
      associated with bovine Deltapapillomavirus.
AB  - Congenital fibropapillomatosis of the gingiva and oral mucosa and epidermal
      hyperplasia of the lip are described, for the first time, in two newborn lambs.
      Expression of the E5 oncoprotein of bovine deltapapillomavirus types 2 (BPV-2)
      and -13 (BPV-13) was detected in both fibropapillomas and the hyperplastic
      epidermal cells suggesting the BPV infection was the cause of the proliferative
      lesions. No DNA sequences of BPV-1 and BPV-14 were detected. Both BPV-2 and BPV
      13 DNA were also amplified from peripheral blood mononuclear cells (PBMCs) of the
      newborn lambs' dams. The concordance between BPV genotypes detected in the blood
      of dam and the oral and skin pathological samples of their offspring suggests
      that a vertical hematogeneous transmission was most likely source of BPV
      infection. Immunoblotting revealed the presence of E5 dimers allowing the viral
      protein to be biologically active. E5 dimers bind and activate the platelet
      derived growth factor beta receptor (PDGFbetaR), a major molecular mechanism
      contributing to disease. The detection of E5 protein within the proliferating
      cells therefore adds further evidence that the BPV infection was the cause of the
      proliferative lesions seen in these lambs. This is the first evidence of vertical
      transmission of BPVs in sheep resulting in a clinical disease.

PMID- 30190494
TI  - Searching the second hit in patients with inherited retinal dystrophies and
      monoallelic variants in ABCA4, USH2A and CEP290 by whole-gene targeted
      sequencing.
AB  - Inherited Retinal Dystrophies are clinically and genetically heterogeneous
      disorders affecting the photoreceptors. Although NGS has shown to be helpful for
      the molecular diagnosis of these conditions, some cases remain unsolved. Among
      these, several individuals harboured monoallelic variants in a recessive gene,
      suggesting that a comprehensive screening could improve the overall diagnosis. In
      order to assess the contribution of non-coding variations in a cohort of 29
      patients, 25 of them with monoallelic mutations, we performed targeted NGS. The
      design comprised the entire genomic sequence of three genes (USH2A, ABCA4 and
      CEP290), the coding exons of 76 genes and two disease-associated intronic regions
      in OFD1 and PRPF31. As a result, likely causative mutations (8 novel) were
      identified in 17 probands (diagnostic rate: 58.62%), including two copy-number
      variations in USH2A (one deletion of exons 22-55 and one duplication of exons 46
      47). Possibly damaging deep-intronic mutations were identified in one family, and
      another with a monoallelic variant harboured causal mutations in a different
      locus. In conclusion, due to the high prevalence of carriers of IRD mutations and
      the results obtained here, sequencing entire genes do not seem to be the approach
      of choice for detecting the second hit in IRD patients with monoallelic variants.

PMID- 30190496
TI  - Ultracompact Graphene-Assisted Tunable Waveguide Couplers with High Directivity
      and Mode Selectivity.
AB  - Graphene distinguishes itself as a promising candidate for realizing tunable
      integrated photonic devices with high flexibility. We propose a set of
      ultracompact tunable on-chip waveguide couplers with mode-selectivity and
      polarization sensitivity around the telecom wavelength of 1.55 MUm, under the
      configuration of graphene-laminated silicon waveguides patterned with gold
      nanoantennas. Versatile couplings can be achieved in a widely tunable fashion
      within a deep-subwavelength area (210 * 210 nm2), by marrying the advantages of
      tight field confinement in plasmonic antennas and the largely tunable carrier
      density of graphene. Incident light signals can be selectively coupled into
      different fundamental modes with good mode quality and high directionality
      exceeding 25 dB. Design scenarios for asymmetric couplings are presented, where
      the operation wavelength can be tuned across a 107-nm range around 1.55 mm by
      altering the chemical potential of graphene from 0 to 1.8 eV. Furthermore, the
      proposed schemes can be leveraged as mode-sensitive on-chip directional waveguide
      signal detectors with an extinction ratio over 10 dB. Our results provide a new
      paradigm upon graphene-assisted tunable integrated photonic applications.

PMID- 30190495
TI  - Characterization of lasR-deficient clinical isolates of Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa is a prevalent opportunistic pathogen that causes fatal
      infections in immunocompromised individuals. Quorum sensing (QS) is a cell-to
      cell communication process that controls virulence gene expression and biofilm
      formation in P. aeruginosa. Here, the QS systems and the relevant virulence
      traits in clinical P. aeruginosa isolates were characterized. Eleven out of the
      ninety-four P. aeruginosa isolates exhibited a biofilm-deficient phenotype. Two
      biofilm-deficient isolates, one from blood and the one from pleural effusion,
      appeared to carry a same mutation in lasR. These two isolates differed in the
      ability to produce QS-regulated virulence factors, but contained the same
      functionally deficient LasR with the truncated C-terminal domains and belonged to
      the same multilocus sequence type (ST227). Chromosomal lasR complementation in
      these lasR mutants verified that lasR inactivation was the sole cause of las
      deficiency. LasR was not absolutely required for rhl signal in these lasR
      mutants, suggesting the presence of lasR-independent QS systems. We provided
      evidence that the virulence gene expression are not regulated in the same manner
      in these isolates. These results support the hypothesis that conventional QS
      hierarchy can be smashed by naturally occurring lasR mutation in clinical P.
      aeruginosa isolates and that complex QS hierarchy may play a role in maintaining
      infection of this opportunistic pathogen.

PMID- 30190497
TI  - Unexpected stability of aqueous dispersions of raspberry-like colloids.
AB  - Aqueous colloidal suspensions, both man-made and natural, are part of our
      everyday life. The applicability of colloidal suspensions, however, is limited by
      the range of conditions over which they are stable. Here we report a novel type
      of highly monodisperse raspberry-like colloids, which are prepared in a single
      step synthesis that relies on simultaneous dispersion and emulsion
      polymerisation. The resulting raspberry colloids behave almost like hard spheres.
      In aqueous solutions, such prepared raspberries show unexpected stability against
      aggregation over large variations of added salt concentrations without addition
      of stabilisers. We present simple Derjaguin-Landau-Verwey-Overbeek (DLVO)
      calculations performed on raspberry-like and smooth colloids showing that this
      stability results from our raspberries' unique morphology, which extends our
      understanding of colloidal stability against salting. Further, the raspberries'
      stability facilitates the formation of superspheres and thin films in which the
      raspberry colloids self-assemble into hexagonally close-packed photonic crystals
      with exquisite reproducibility.

PMID- 30190499
TI  - Ultra-Wideband Impulse Radar Through-Wall Detection of Vital Signs.
AB  - This paper presents a new system for the detection of human respiration behind
      obstacles using impulse ultra-wideband (UWB) radar. In complex environments, low
      signal-to-noise ratios (SNRs) as they can result in significant errors in the
      respiration, heartbeat frequency, and range estimates. To improve the
      performance, the complex signal demodulation (CSD) technique is extended by
      employing the signal logarithm and derivative. A frequency accumulation (FA)
      method is proposed to suppress mixed products of the heartbeat and respiration
      signals and spurious respiration signal harmonics. The respiration frequency is
      estimated using the phase variations in the received signal, and a discrete short
      time Fourier transform (DSFT) is used to estimate the range. The performance of
      the proposed system is evaluated along with that of several well-known techniques
      in the literature.

PMID- 30190498
TI  - Imaging of Murine Whole Lung Fibrosis by Large Scale 3D Microscopy aided by
      Tissue Optical Clearing.
AB  - Pulmonary fibrosis, characterized by excessive collagen deposition in the lungs,
      comprises a key and debilitating component of chronic lung diseases. Methods are
      lacking for the direct visualization of fibrillar collagen throughout the whole
      murine lung, a capability that would aid the understanding of lung fibrosis. We
      combined an optimized organ-level optical clearing (OC) approach with large
      scale, label-free multiphoton microscopy (MPM) and second harmonic generation
      microscopy (SHGM) to reveal the complete network of fibrillar collagen in whole
      murine lungs. An innate inflammation-driven model based on repetitive poly(I:C)
      challenge was evaluated. Following OC, mosaic MPM/SHGM imaging with 3D
      reconstruction and whole organ quantitative analysis revealed significant
      differences in collagen deposition between PBS and poly(I:C) treated lungs.
      Airway specific analysis in whole lung acquisitions revealed significant sub
      epithelial fibrosis evident throughout the proximal conductive and distal airways
      with higher collagen deposition in the poly(I:C) group vs PBS group. This study
      establishes a new, powerful approach based on OC and MPM/SHGM imaging for 3D
      analysis of lung fibrosis with macroscopic views of lung pathology based on
      microscopy and providing a new way to analyze the whole lung while avoiding
      regional sampling bias.

PMID- 30190500
TI  - Nuclear Nestin deficiency drives tumor senescence via lamin A/C-dependent nuclear
      deformation.
AB  - Emerging evidence has revealed that Nestin not only serves as a biomarker for
      multipotent stem cells, but also regulates cell proliferation and invasion in
      various tumors. However, the mechanistic contributions of Nestin to cancer
      pathogenesis are still unknown. In the present study, previously thought to
      reside exclusively in the cytoplasm, Nestin can also be found in the nucleus and
      participate in protecting tumor cells against cellular senescence. Specifically,
      we reveal that Nestin has a nuclear localization signal (aa318-aa347) at the
      downstream of rod domain. We then find nuclear Nestin could interact with lamin
      A/C. Mechanistic investigations demonstrate that Nestin depletion results in the
      activation of cyclin-dependent kinase 5 (Cdk5), which causes the phosphorylation
      of lamin A/C (mainly at S392 site) and its subsequent translocation to the
      cytoplasm for degradation. The findings establish a role for nuclear Nestin in
      tumor senescence, which involves its nucleus-localized form and interaction with
      lamin A/C.

PMID- 30190501
TI  - Visual percepts modify iconic memory in humans.
AB  - Our visual system briefly retains a trace of a stimulus after it disappears. This
      phenomenon is known as iconic memory and its contents are thought to be
      temporally integrated with subsequent visual inputs to produce a single composite
      representation. However, there is little consensus on the temporal integration
      between iconic memory and subsequent visual inputs. Here, we show that iconic
      memory revises its contents depending upon the configuration of the newly
      produced single representation with particular temporal characteristics. The
      Poggendorff illusion, in which two collinear line segments are perceived as non
      collinear by an intervening rectangle, was observed when the rectangle was
      presented during a period spanning from 50 ms before to 200 ms after the
      presentation of the line segments. The illusion was most prominent when the
      rectangle was presented approximately 100 to 150 ms after the line segments.
      Furthermore, the illusion was observed at the center of a moving object, but only
      when the line segments were presented before the rectangle. These results
      indicate that the contents of iconic memory are susceptible to the modulatory
      influence of subsequent visual inputs before being translated into conscious
      perception in a time-locked manner both in retinotopic and non-retinotopic,
      object-centered frames of reference.

PMID- 30190502
TI  - Incidence and Radiological Predictors of Concomitant Meniscal and Cruciate
      Ligament Injuries in Operative Tibial Plateau Fractures: A Prospective Diagnostic
      Study.
AB  - The aim of this prospective study was to determine the incidence of meniscal and
      cruciate ligament injuries in operative tibial plateau fractures detected using
      knee arthroscopy, and to identify the radiological predictors observed on CT
      images. From January 2016 to February 2017, a total of 102 closed tibial plateau
      fractures were enrolled in this prospective protocol. Each patient underwent
      arthroscopic examination following the tibial plateau internal fixation.
      Univariate analysis and multivariable logistic regression were used to assess the
      association between imaging parameters and soft-tissue injuries. The menisci were
      traumatically injured in 52.9% of subjects (54 of 102) and the cruciate ligaments
      injured in 22.5% (23 of 102). Significantly higher injury rates for bucket-handle
      meniscal tears were observed in Schatzker type VI fractures (P = 0.04). Greater
      risk of lateral meniscus injury was observed in patients with >6.3 mm of lateral
      joint depression. Greater risk of ACL injury when the volumetric lateral joint
      depression was <=209.5 mm2 and/or with >5.7 mm lateral joint widening. Associated
      meniscal and ligament injuries were commonly seen among operative tibial plateau
      fractures. Preoperative CT measurements might help predict a higher risk of
      meniscus and ACL injury, providing guidance to the surgeon to look for and to be
      prepared to treat such injuries.

PMID- 30190503
TI  - The quaternary structure of Thermus thermophilus aldehyde dehydrogenase is
      stabilized by an evolutionary distinct C-terminal arm extension.
AB  - Aldehyde dehydrogenases (ALDH) form a superfamily of dimeric or tetrameric
      enzymes that catalyze the oxidation of a broad range of aldehydes into their
      corresponding carboxylic acids with the concomitant reduction of the cofactor
      NAD(P) into NAD(P)H. Despite their varied polypeptide chain length and
      oligomerisation states, ALDHs possess a conserved architecture of three domains:
      the catalytic domain, NAD(P)+ binding domain, and the oligomerization domain.
      Here, we describe the structure and function of the ALDH from Thermus
      thermophilus (ALDHTt) which exhibits non-canonical features of both dimeric and
      tetrameric ALDH and a previously uncharacterized C-terminal arm extension forming
      novel interactions with the N-terminus in the quaternary structure. This unusual
      tail also interacts closely with the substrate entry tunnel in each monomer
      providing further mechanistic detail for the recent discovery of tail-mediated
      activity regulation in ALDH. However, due to the novel distal extension of the
      tail of ALDHTt and stabilizing termini-interactions, the current model of tail
      mediated substrate access is not apparent in ALDHTt. The discovery of such a long
      tail in a deeply and early branching phylum such as Deinococcus-Thermus indicates
      that ALDHTt may be an ancestral or primordial metabolic model of study. This
      structure provides invaluable evidence of how metabolic regulation has evolved
      and provides a link to early enzyme regulatory adaptations.

PMID- 30190504
TI  - Co-culture models illustrate the digestion of Gemmata spp. by phagocytes.
AB  - Gemmata spp. bacteria thrive in the same aquatic environments as free-living
      amoebae. DNA-based detection of Gemmata spp. sequences in the microbiota of the
      human digestive tract and blood further questioned the susceptibility of Gemmata
      spp. to phagocytes. Here, Gemmata obscuriglobus and Gemmata massiliana were co
      cultured with the amoebae Acanthamoeba polyphaga, Acanthamoeba castellanii,
      Acanthamoeba griffini and THP-1 macrophage-like phagocytes. All experiments were
      performed in five independant replicates. The ratio amoeba/bacteria was 1:20 and
      the ratio THP-1/bacteria was 1:10. After a 2-hour co-culture, extracellular
      bacteria were killed by kanamycin or amikacin and eliminated. The intracellular
      location of Gemmata bacteria was specified by confocal microscopy. Microscopic
      enumerations and culture-based enumerations of colony-forming units were
      performed at T = 0, 1, 2, 3, 4, 8, 16, 24, 48 and 72 hours post-infection. Then,
      Gemmata bacteria were engulfed into the phagocytes' cytoplasmic vacuoles, more
      than (98 +/- 2)% of Gemmata bacteria, compared to controls, were destroyed by
      phagocytic cells after a 48-h co-culture according to microscopy and culture
      results, and no positive culture was observed at T = 72-hours. Under our co
      culture conditions, Gemmata bacteria were therefore susceptible to the
      environmental and host phagocytes here investigated. These data suggest that
      these Acanthamoeba species and THP-1 cells cannot be used to isolate G.
      massiliana and G. obscuriglobus under the co-culture conditions applied in this
      study. Although the THP-1 response can point towards potential responses that
      might occur in vivo, these responses should first bevalidated by in vivo studies
      to draw definite conclusions.

PMID- 30190506
TI  - The transcription factor SoxD controls neuronal guidance in the Drosophila visual
      system.
AB  - Precise control of neurite guidance during development is essential to ensure
      proper formation of neuronal networks and correct function of the central nervous
      system (CNS). How neuronal projections find their targets to generate appropriate
      synapses is not entirely understood. Although transcription factors are key
      molecules during neurogenesis, we do not know their entire function during the
      formation of networks in the CNS. Here, we used the Drosophila melanogaster optic
      lobe as a model for understanding neurite guidance during development. We
      assessed the function of Sox102F/SoxD, the unique Drosophila orthologue of the
      vertebrate SoxD family of transcription factors. SoxD is expressed in immature
      and mature neurons in the larval and adult lobula plate ganglia (one of the optic
      lobe neuropils), but is absent from glial cells, neural stem cells and
      progenitors of the lobula plate. SoxD RNAi knockdown in all neurons results in a
      reduction of the lobula plate neuropil, without affecting neuronal fate. This
      morphological defect is associated with an impaired optomotor response of adult
      flies. Moreover, knocking down SoxD only in T4/T5 neuronal types, which control
      motion vision, affects proper neurite guidance into the medulla and lobula. Our
      findings suggest that SoxD regulates neurite guidance, without affecting neuronal
      fate.

PMID- 30190505
TI  - Tree rings reveal globally coherent signature of cosmogenic radiocarbon events in
      774 and 993 CE.
AB  - Though tree-ring chronologies are annually resolved, their dating has never been
      independently validated at the global scale. Moreover, it is unknown if
      atmospheric radiocarbon enrichment events of cosmogenic origin leave
      spatiotemporally consistent fingerprints. Here we measure the 14C content in 484
      individual tree rings formed in the periods 770-780 and 990-1000 CE. Distinct 14C
      excursions starting in the boreal summer of 774 and the boreal spring of 993
      ensure the precise dating of 44 tree-ring records from five continents. We also
      identify a meridional decline of 11-year mean atmospheric radiocarbon
      concentrations across both hemispheres. Corroborated by historical eye-witness
      accounts of red auroras, our results suggest a global exposure to strong solar
      proton radiation. To improve understanding of the return frequency and intensity
      of past cosmic events, which is particularly important for assessing the
      potential threat of space weather on our society, further annually resolved 14C
      measurements are needed.

PMID- 30190508
TI  - Cardiosphere-derived cells suppress allogeneic lymphocytes by production of PGE2
      acting via the EP4 receptor.
AB  - Cardiosphere-derived cells (CDCs) are a cardiac progenitor cell population, which
      have been shown to possess cardiac regenerative properties and can improve heart
      function in a variety of cardiac diseases. Studies in large animal models have
      predominantly focussed on using autologous cells for safety, however allogeneic
      cell banks would allow for a practical, cost-effective and efficient use in a
      clinical setting. The aim of this work was to determine the immunomodulatory
      status of these cells using CDCs and lymphocytes from 5 dogs. CDCs expressed MHC
      I but not MHC II molecules and in mixed lymphocyte reactions demonstrated a lack
      of lymphocyte proliferation in response to MHC-mismatched CDCs. Furthermore, MHC
      mismatched CDCs suppressed lymphocyte proliferation and activation in response to
      Concanavalin A. Transwell experiments demonstrated that this was predominantly
      due to direct cell-cell contact in addition to soluble mediators whereby CDCs
      produced high levels of PGE2 under inflammatory conditions. This led to down
      regulation of CD25 expression on lymphocytes via the EP4 receptor. Blocking
      prostaglandin synthesis restored both, proliferation and activation (measured via
      CD25 expression) of stimulated lymphocytes. We demonstrated for the first time in
      a large animal model that CDCs inhibit proliferation in allo-reactive lymphocytes
      and have potent immunosuppressive activity mediated via PGE2.

PMID- 30190509
TI  - Role of dimensional crossover on spin-orbit torque efficiency in magnetic
      insulator thin films.
AB  - Magnetic insulators (MIs) attract tremendous interest for spintronic applications
      due to low Gilbert damping and the absence of Ohmic loss. Spin-orbit torques
      (SOTs) on MIs are more intriguing than magnetic metals since SOTs cannot be
      transferred to MIs through direct injection of electron spins. Understanding of
      SOTs on MIs remains elusive, especially how SOTs scale with the MI film
      thickness. Here, we observe the critical role of dimensionality on the SOT
      efficiency by studying the MI layer thickness-dependent SOT efficiency in
      tungsten/thulium iron garnet (W/TmIG) bilayers. We show that the TmIG thin film
      evolves from two-dimensional to three-dimensional magnetic phase transitions as
      the thickness increases. We report the significant enhancement of the measured
      SOT efficiency as the TmIG thickness increases, which is attributed to the
      increase of the magnetic moment density. We demonstrate the current-induced SOT
      switching in the W/TmIG bilayers with a TmIG thickness up to 15 nm.

PMID- 30190507
TI  - The involvement of the low-oxygen-activated locus of Burkholderia cenocepacia in
      adaptation during cystic fibrosis infection.
AB  - Chronic infection with opportunistic pathogens including Burkholderia cepacia
      complex (Bcc) is a hallmark of cystic fibrosis (CF). We investigated the adaptive
      mechanisms facilitating chronic lung infection in sequential Bcc isolates from
      two siblings with CF (P1 and P2), one of whom also experienced intermittent blood
      stream infections (P2). We previously showed increased lung cell attachment with
      colonisation time in both P1 and P2. WGS analysis confirmed that the isolates are
      closely related. Twelve genes showed three or more mutations, suggesting these
      were genes under selection. Single nucleotide polymorphisms (SNVs) in 45
      regulatory genes were also observed. Proteomic analysis showed that the abundance
      of 149 proteins increased over 61-months in sputum isolates, and both time- and
      source-related alterations in protein abundance between the second patient's
      isolates. A consistent time-dependent increase in abundance of 19 proteins
      encoded by a low-oxygen-activated (lxa) locus was observed in both sets of
      isolates. Attachment was dramatically reduced in a B. cenocepacia K56-2Deltalxa
      locus deletion mutant, further indicating that it encodes protein(s) involved in
      host-cell attachment. Time-related changes in virulence in Galleria mellonella or
      motility were not observed. We conclude that the lxa-locus, associated with
      anoxic persistence in vitro, plays a role in host-cell attachment and adaptation
      to chronic colonization in the hypoxic niche of the CF lung.

PMID- 30190512
TI  - The effect of gene therapy on postoperative recurrence of small hepatocellular
      carcinoma (less than 5cm).
AB  - To observe the curative effect of surgery combined with gene therapy on small
      hepatocellular carcinoma. Seventy-seven patients with small hepatocellular
      carcinoma (diameter < 5 cm) underwent surgical resection. The tumor located at
      the edge of the liver was treated by local excision or irregular hepatectomy. The
      tumor in the center of the liver was resected by hepatic lobectomy in order to
      ensure at least a 2-cm safety margin. Fifty-four patients underwent gene therapy
      (gene group) one or two times before operation, whereas 23 patients underwent
      surgery alone (control group) selected by themselves. The injectable gene was
      made of ADV-TK (adenovirus containing thymidine kinase suicide gene, with a
      concentration of 5 * 1012/ml). The prognosis of patients was analyzed by imaging
      twice a year. In the gene group, the 1-, 3-, and 5-year survival rates were 91.4,
      63.6, and 52.1%. In the control group, the survival rates were 84.3, 54.4, and
      32.6%, respectively. There was a significant difference in the overall survival
      rates between two groups. Factors associated with overall survival in univariate
      analysis included bilirubin, prothrombin activity, cirrhosis, and gene therapy (P
      < 0.05). In the multivariate analysis, it included cirrhosis, gene therapy, and
      bilirubin. The gene therapy hepatocellular carcinoma patients with a diameter < 5
      cm could significantly reduce recurrence after operation. It was worthy of being
      popularized.

PMID- 30190511
TI  - Biallelic inactivation of the retinoblastoma gene results in transformation of
      chronic myelomonocytic leukemia to a blastic plasmacytoid dendritic cell
      neoplasm: shared clonal origins of two aggressive neoplasms.

PMID- 30190510
TI  - The contribution of hormone sensitive lipase to adipose tissue lipolysis and its
      regulation by insulin in periparturient dairy cows.
AB  - Hormone sensitive lipase (HSL) activation is part of the metabolic adaptations to
      the negative energy balance common to the mammalian periparturient period. This
      study determined HSL contribution to adipose tissue (AT) lipolysis and how
      insulin regulates its activity in periparturient dairy cows. Subcutaneous AT
      (SCAT) samples were collected at 11 d prepartum (dry) and 11 (fresh) and 24 d
      (lactation) postpartum. Basal and stimulated lipolysis (ISO) responses were
      determined using explant cultures. HSL contribution to lipolysis was assessed
      using an HSL inhibitor (CAY). Basal lipolysis was higher in SCAT at dry compared
      with fresh. CAY inhibited basal lipolysis negligibly at dry, but at fresh and
      lactation it reduced basal lipolysis by 36.1 +/- 4.51% and 43.1 +/- 4.83%,
      respectively. Insulin inhibited lipolysis more pronouncedly in dry compared to
      fresh. Results demonstrate that HSL contribution to basal lipolysis is negligible
      prepartum. However, HSL is a major driver of SCAT lipolytic responses postpartum.
      Lower basal lipolysis postpartum suggests that reduced lipogenesis is an
      important contributor to fatty acid release from SCAT. Loss of adipocyte
      sensitivity to the antilipolytic action of insulin develops in the early
      lactation period and supports a state of insulin resistance in AT of cows during
      the first month postpartum.

PMID- 30190513
TI  - Tissue-specific induced DNA methyltransferase 1 (Dnmt1) in endocrine pancreas by
      RCAS-TVA-based somatic gene transfer system promotes beta-cell proliferation.
AB  - We reported that inactivation of menin (the protein product of MEN1) increases
      activity of Dnmt1 and mediates DNA hypermethylation in the development of
      multiple endocrine neoplasia type 1 (MEN1) syndrome. We have developed a RCAS-TVA
      based somatic gene transfer system that enables tissue-specific delivery of Dnmt1
      to individual beta-cells of the pancreas in a RIP-TVA mouse model. In the present
      study, we mediated Dnmt1 expression in islet beta-cells in RIP-TVA mice by
      utilizing the RCAS-TVA system to test if the upregulation of Dnmt1 can promote
      beta-cell proliferation. In vitro, we demonstrated that upregulation of Dnmt1
      increased beta-cell proliferation. In vivo, our results showed that the levels of
      serum insulin were increased in the RIP-TVA mice with RCASBP-Dnmt1 infection
      compared with wild-type control mice with RCASBP-Dnmt1 infection. Furthermore, we
      confirmed that mRNA and protein expression of Dnmt1 as well as Dnmt1 enzyme
      activity were upregulated in the RIP-TVA mice with RCASBP-Dnmt1 infection
      compared with wild-type control mice with RCASBP-Dnmt1 infection. Finally, we
      demonstrated that upregulation of Dnmt1 resulted in hyperplasia through beta-cell
      proliferation. We conclude that the upregulation of Dnmt1 promotes islet beta
      cell proliferation and targeting Dnmt1 may be a promising therapy for patients
      suffering from pancreatic neuroendocrine tumors.

PMID- 30190515
TI  - Spatial-temporal dynamics of carbon emissions and carbon sinks in economically
      developed areas of China: a case study of Guangdong Province.
AB  - This study analysed spatial-temporal dynamics of carbon emissions and carbon
      sinks in Guangdong Province, South China. The methodology was based on land
      use/land cover data interpreted from continuous high-resolution satellite images
      and energy consumption statistics, using carbon emission/sink factor method. The
      results indicated that: (1) From 2005 to 2013, different land use/land cover
      types in Guangdong experienced varying degrees of change in area, primarily the
      expansion of built-up land and shrinkage of forest land and grassland; (2) Total
      carbon emissions increased sharply, from 76.11 to 140.19 TgC yr-1 at the
      provincial level, with an average annual growth rate of 10.52%, while vegetation
      carbon sinks declined slightly, from 54.52 to 53.20 TgC yr-1. Both factors showed
      significant regional differences, with Pearl River Delta and North Guangdong
      contributing over 50% to provincial carbon emissions and carbon sinks,
      respectively; (3) Correlation analysis showed social-economic factors (GDP per
      capita and permanent resident population) have significant positive impacts on
      carbon emissions at the provincial and city levels; (4) The relationship between
      economic growth and carbon emission intensity suggests that carbon emission
      efficiency in Guangdong improves with economic growth. This study provides new
      insight for Guangdong to achieve carbon reduction goals and realize low-carbon
      development.

PMID- 30190516
TI  - SeesawPred: A Web Application for Predicting Cell-fate Determinants in Cell
      Differentiation.
AB  - Cellular differentiation is a complex process where a less specialized cell
      evolves into a more specialized cell. Despite the increasing research effort,
      identification of cell-fate determinants (transcription factors (TFs) determining
      cell fates during differentiation) still remains a challenge, especially when
      closely related cell types from a common progenitor are considered. Here, we
      develop SeesawPred, a web application that, based on a gene regulatory network
      (GRN) model of cell differentiation, can computationally predict cell-fate
      determinants from transcriptomics data. Unlike previous approaches, it allows the
      user to upload gene expression data and does not rely on pre-compiled reference
      data sets, enabling its application to novel differentiation systems. SeesawPred
      correctly predicted known cell-fate determinants on various cell differentiation
      examples in both mouse and human, and also performed better compared to state-of
      the-art methods. The application is freely available for academic, non-profit use
      at http://seesaw.lcsb.uni.lu.

PMID- 30190514
TI  - Linking prostate cancer cell AR heterogeneity to distinct castration and
      enzalutamide responses.
AB  - Expression of androgen receptor (AR) in prostate cancer (PCa) is heterogeneous
      but the functional significance of AR heterogeneity remains unclear. Screening
      ~200 castration-resistant PCa (CRPC) cores and whole-mount sections (from 89
      patients) reveals 3 AR expression patterns: nuclear (nuc-AR), mixed
      nuclear/cytoplasmic (nuc/cyto-AR), and low/no expression (AR-/lo). Xenograft
      modeling demonstrates that AR+ CRPC is enzalutamide-sensitive but AR-/lo CRPC is
      resistant. Genome editing-derived AR+ and AR-knockout LNCaP cell clones exhibit
      distinct biological and tumorigenic properties and contrasting responses to
      enzalutamide. RNA-Seq and biochemical analyses, coupled with experimental
      combinatorial therapy, identify BCL-2 as a critical therapeutic target and
      provide proof-of-concept therapeutic regimens for both AR+/hi and AR-/lo CRPC.
      Our study links AR expression heterogeneity to distinct castration/enzalutamide
      responses and has important implications in understanding the cellular basis of
      prostate tumor responses to AR-targeting therapies and in facilitating
      development of novel therapeutics to target AR-/lo PCa cells/clones.

PMID- 30190517
TI  - Imaging the nanoscale phase separation in vanadium dioxide thin films at
      terahertz frequencies.
AB  - Vanadium dioxide (VO2) is a material that undergoes an insulator-metal transition
      upon heating above 340 K. It remains debated as to whether this electronic
      transition is driven by a corresponding structural transition or by strong
      electron-electron correlations. Here, we use apertureless scattering near-field
      optical microscopy to compare nanoscale images of the transition in VO2 thin
      films acquired at both mid-infrared and terahertz frequencies, using a home-built
      terahertz near-field microscope. We observe a much more gradual transition when
      THz frequencies are utilized as a probe, in contrast to the assumptions of a
      classical first-order phase transition. We discuss these results in light of
      dynamical mean-field theory calculations of the dimer Hubbard model recently
      applied to VO2, which account for a continuous temperature dependence of the
      optical response of the VO2 in the insulating state.

PMID- 30190518
TI  - Impaired microcirculation after subarachnoid hemorrhage in an in vivo animal
      model.
AB  - The influence of aneurysmal subarachnoid hemorrhage (SAH) on brain
      microcirculation has not yet been systematically investigated. We established an
      animal model to examine (1) the brain surface microcirculation (2) the influences
      of cerebrospinal fluid (CSF) from aneurysmal SAH on the brain surface
      microcirculation. A rat SAH model was induced by injection of autologous arterial
      blood into the cisterna magnum, and the brain surface microcirculation was
      evaluated by a capillary videoscope with craniotomy at the fronto-parietal
      region. CSF from SAH rats and SAH patients was applied on the brain surface of
      naive rats to assess the resulting microcirculatory changes. In the SAH rats,
      diffuse constriction of cortical arterioles within 24 hours of SAH was observed.
      Similar patterns of microcirculation impairment were induced on normal rat brain
      surfaces via application of CSF from SAH rats and SAH patients. Furthermore, the
      proportion of subjects with arteriolar vasoconstriction was significantly higher
      in the group of SAH patients with delayed ischemic neurological deficits (DIND)
      than in those without DIND (p < 0.001). This study demonstrated impaired
      microcirculation on brain surface arterioles in a rat model of SAH. CSF from SAH
      rats and patients was responsible for impairment of brain surface
      microcirculation.

PMID- 30190520
TI  - Calcium crystal deposition diseases - beyond gout.
AB  - The most common types of calcium-containing crystals that are associated with
      joint and periarticular disorders are calcium pyrophosphate dihydrate (CPP) and
      basic calcium phosphate (BCP) crystals. Several diverse but difficult-to-treat
      acute and chronic arthropathies and other clinical syndromes are associated with
      the deposition of these crystals. Although the pathogenic mechanism of calcium
      crystal deposition is partially understood, much remains to be investigated, as
      no drug is available to prevent crystal deposition, permit crystal dissolution or
      specifically target the pathogenic effects that result in the clinical
      manifestations. In this Review, the main clinical manifestations of CPP and BCP
      crystal deposition are discussed, along with the biological effects of these
      crystals, current therapeutic approaches and future directions in therapy.

PMID- 30190521
TI  - Epigenetic predictive biomarkers for response or outcome to platinum-based
      chemotherapy in non-small cell lung cancer, current state-of-art.
AB  - Platinum-based chemotherapy is commonly used to treat non-small cell lung cancer
      (NSCLC). However, its efficacy is limited and no molecular biomarkers that
      predict response are available. In this review, we summarize current knowledge
      concerning potential epigenetic predictive markers for platinum-based
      chemotherapy response in NSCLC. A systematic search of PubMed and
      ClinicalTrials.gov using keywords "non-small cell lung cancer" combined with
      "chemotherapy predictive biomarkers", "chemotherapy epigenetics biomarkers",
      "chemotherapy microRNA biomarkers", "chemotherapy DNA methylation" and
      "chemotherapy miRNA biomarkers" revealed 1740 articles from PubMed and 36
      clinical trials. Finally, 22 papers and no trials fulfilled the review criteria.
      Among miRNA, combination of miR-1290, miR-196b and miR-135a in tumor tissue, and
      miR-21, miR-25, miR27b, and miR-326 in plasma were predictive for response to
      platinum-based chemotherapy in advanced NSCLC. RASSF1A methylation measured in
      tumor or blood was predictive for response to neoadjuvant chemotherapy. These
      biomarkers remain experimental and none have been tested in a prospective trial.

PMID- 30190519
TI  - Overexpression of BoNAC019, a NAC transcription factor from Brassica oleracea,
      negatively regulates the dehydration response and anthocyanin biosynthesis in
      Arabidopsis.
AB  - NACs are one of the largest transcription factor families in plants and are
      involved in the response to abiotic stress. BoNAC019, a homologue of AtNAC019,
      was isolated from cabbage (Brassica oleracea). BoNAC019 was localized in the
      nucleus and functioned as a transcriptional activator. The expression of BoNAC019
      was induced by dehydration, salt, abscisic acid (ABA), and H2O2 treatments.
      BoNAC019 overexpressing plants were generated to explore the function of BoNAC019
      in response to drought stress. Overexpression (OE) of BoNAC019 reduced drought
      tolerance with lower survival rate, higher water loss rate, lower proline content
      and ABA content. The seed germination and root length assays of BoNAC019-OE
      plants showed decreased sensitivity to ABA. Under drought condition, antioxidant
      enzymes and anthocyanin content decreased in BoNAC019 -OE plants, resulting in
      the accumulation of more reactive oxygen species (ROS), which cause damage to
      plants. Several stress-responsive genes, antioxidant enzymatic genes, anthocyanin
      biosynthetic genes and ABA signaling genes were down-regulated under drought
      condition while the ABA catabolism genes were induced in BoNAC019-OE plants under
      both normal and drought conditions. Our results demonstrated that BoNAC019 might
      participated in regulating drought tolerance by inducing ABA catabolism genes and
      decreasing ABA content.

PMID- 30190522
TI  - A tRNA-based multiplex sgRNA expression system in zebrafish and its application
      to generation of transgenic albino fish.
AB  - The CRISPR/Cas9 system can be introduced into zebrafish as transgenes. Namely,
      expression of single-guide RNA (sgRNA) and controlled expression of Cas9 in
      transgenic zebrafish enables the study of gene functions in specific cell types.
      This transgenic CRISPR/Cas9 approach would be more useful if multiple sgRNAs
      could be expressed simultaneously since we could knock-out a gene more
      efficiently or disrupt multiple genes simultaneously. Here we describe a novel
      system to express multiple sgRNAs efficiently in zebrafish, that relies on the
      endogenous tRNA processing machinery. We cloned nine endogenous zebrafish tRNA
      genes, fused them to sgRNAs, and demonstrated that an active sgRNA can be
      produced from a precursor transcript containing either of these tRNAs. To show a
      proof of principle, we constructed transgenic fish expressing Cas9 under the
      control of the ubiquitin promoter and a single transcript containing three
      distinct sgRNAs, that targeted the slc45a2 (albino) gene, fused to tRNAs under
      the control of the U6 promoter. We found that the Tg(ubb:SpCas9,u6c:3xslc45a2
      sgRNA) harbored mutations in all of the target sites in the albino gene and
      showed nearly complete albino phenotypes, which were amenable to imaging
      experiments. Thus, the tRNA-based multiplex sgRNA expression system should
      facilitate gene knock-out studies in transgenic zebrafish.

PMID- 30190523
TI  - Dynamic capillary assembly of colloids at interfaces with 10,000g accelerations.
AB  - High-rate deformation of soft matter is an emerging area central to our
      understanding of far-from-equilibrium phenomena during shock, fracture, and phase
      change. Monolayers of colloidal particles are a convenient two-dimensional model
      system to visualise emergent behaviours in soft matter, but previous studies have
      been limited to slow deformations. Here we probe and visualise the evolution of a
      monolayer of colloids confined at a bubble surface during high-rate deformation
      driven by ultrasound. We observe the emergence of a transient network of strings,
      and use discrete particle simulations to show that it is caused by a delicate
      interplay of dynamic capillarity and hydrodynamic interactions between particles
      oscillating at high frequency. Remarkably for a colloidal system, we find
      evidence of inertial effects, caused by accelerations approaching 10,000g. These
      results also suggest that extreme deformation of soft matter offers new
      opportunities for pattern formation and dynamic self-assembly.

PMID- 30190525
TI  - Recoil-proton track imaging as a new way for neutron spectrometry measurements.
AB  - Recoil-proton track imaging (RPTI) is an attractive technique to optically record
      the tracks of recoil protons in scintillation gas by using realtime imaging
      devices. For the first time, its use as an online nuclear track detector for
      neutron spectrometry measurements (NSM) is explored. Based on the RPTI
      methodology for NSM, a very basic detector system is designed, consisting of the
      neutron-to-proton recoil system and proton track imaging system. Satisfactory
      performance of the RPTI neutron spectrometer has been examined with a series of
      Monte Carlo simulations. Moreover, using well-defined line-proton sources from a
      tandem accelerator, the capability of the detector for imaging proton tracks at
      the single-particle level in real time has been validated in preliminary
      experiments. From the clear single proton tracks in the images, the proton ranges
      were easily distinguished, and precise proton energy spectra were unfolded,
      laying a solid experimental foundation for the future implementation of NSM.

PMID- 30190524
TI  - mGlu1 Receptors Monopolize the Synaptic Control of Cerebellar Purkinje Cells by
      Epigenetically Down-Regulating mGlu5 Receptors.
AB  - In cerebellar Purkinje cells (PCs) type-1 metabotropic glutamate (mGlu1)
      receptors play a key role in motor learning and drive the refinement of synaptic
      innervation during postnatal development. The cognate mGlu5 receptor is absent in
      mature PCs and shows low expression levels in the adult cerebellar cortex. Here
      we found that mGlu5 receptors were heavily expressed by PCs in the early
      postnatal life, when mGlu1alpha receptors were barely detectable. The
      developmental decline of mGlu5 receptors coincided with the appearance of
      mGlu1alpha receptors in PCs, and both processes were associated with specular
      changes in CpG methylation in the corresponding gene promoters. It was the mGlu1
      receptor that drove the elimination of mGlu5 receptors from PCs, as shown by data
      obtained with conditional mGlu1alpha receptor knockout mice and with targeted
      pharmacological treatments during critical developmental time windows. The
      suppressing activity of mGlu1 receptors on mGlu5 receptor was maintained in
      mature PCs, suggesting that expression of mGlu1alpha and mGlu5 receptors is
      mutually exclusive in PCs. These findings add complexity to the the finely tuned
      mechanisms that regulate PC biology during development and in the adult life and
      lay the groundwork for an in-depth analysis of the role played by mGlu5 receptors
      in PC maturation.

PMID- 30190526
TI  - Diabetes knowledge and its association with the weight status among residents of
      Jeddah City, Saudi Arabia.
AB  - OBJECTIVE: To examine the association of weight status with level of diabetes
      knowledge (symptoms and complications) among residents of Jeddah City, Saudi
      Arabia. METHODS: In a cross-sectional study, a questionnaire assessing
      sociodemographic and health characteristics and knowledge about diabetes and its
      symptoms and complications was utilized. Data of 3978 adults, 18 years of age or
      older, were collected from public mall sites in Jeddah city and surrounding
      areas. Participants were divided into three tertiles based on their knowledge
      scores. Weight and height were measured following standardized procedures, and
      body weight categories were defined based on body mass index (BMI). The
      association between weight status and tertiles of diabetes knowledge was examined
      using multinomial logistic regression analysis. RESULTS: Compared to normal
      weight participants, participants who were underweight, overweight, or obese, did
      not differ with regards to knowledge about diabetes symptoms. Adjusted models
      showed that overweight and obese participants had lower odds of being in the
      lowest tertile of knowledge about diabetes complications compared to normal
      weight participants (OR: 0.71, 95% CI: 0.58-0.86 and OR: 0.64, 95% CI: 0.51-0.79,
      respectively). With regards to general knowledge about diabetes, the knowledge of
      participants who were underweight did not differ when compared to normal-weight
      participants. Overweight and obese participants had lower odds of being in the
      lowest tertile of general knowledge about diabetes compared to normal-weight
      participants (OR: 0.78, 95% CI: 0.62-0.97 and OR: 0.60, 95% CI: 0.47-0.76,
      respectively). CONCLUSIONS: Overweight and obese individuals have better
      knowledge about diabetes compared to normal-weight individuals. Public health
      programs need to take into account the level of diabetes knowledge and tailor
      interventions to aid behavior and lifestyle change.

PMID- 30190527
TI  - Different contributions of autophagy to retinal ganglion cell death in the
      diabetic and glaucomatous retinas.
AB  - Diabetes mellitus and glaucoma are the two major causes of selective retinal
      ganglion cell (RGC) death. To determine the relationship between autophagy and
      RGC death, we compared autophagy and the related molecular pathways in diabetic
      and glaucomatous retinas and examined their effect on RGC survival. Biochemical
      analysis of microtubule-associated protein light chain 3 (LC3)-II and beclin-1
      were observed. To determine the pathways involved in autophagy induction,
      adenosine monophosphate-activated protein kinase (AMPK) and the mechanistic
      target of rapamycin (mTOR) were also explored. Beclin-1 and the LC3B-II to LC3B-I
      ratio significantly elevated at 4 and 8 weeks after glaucoma induction; however,
      only a slight increase was apparent in the diabetic retina. Significant
      upregulation of phosphorylated AMPK and downregulation of phosphorylated mTOR was
      evident in the diabetic retina. After autophagy was inhibited with 3
      methyladenine (3-MA), apoptosis of RGCs was significantly increased in the
      diabetic retinas. However, 3-MA inhibition of autophagy decreased the apoptosis
      of RGCs in glaucomatous retinas. Therefore, our results suggest that RGC death is
      differentially regulated by autophagy and that the pathways involved differ
      depending on the triggering injury.

PMID- 30190528
TI  - Anti-corrosive and oil sensitive coatings based on epoxy/polyaniline/magnetite
      clay composites through diazonium interfacial chemistry.
AB  - Epoxy polymer nanocomposites filled with magnetite (Fe3O4) clay (B), named (B-DPA
      PANI@Fe3O4) have been prepared at different filler loading (0.1, 0.5, 1, 3, 5 wt.
      %). The surface modification of clay by polyaniline (PANI) is achieved in the
      presence of 4-diphenylamine diazonium salt (DPA). The effects of the nanofiller
      loading on Tensile, mechanical and dielectric properties were systematically
      studied. Improved properties was highlighted for all reinforced samples. The
      addition of only 3 wt. % of the filler enhanced the tensile strength of the
      composites by 256%, and the glass transition temperature Tg by 37%. The
      dielectric spectra over a broad frequency showed a robust interface between the
      hybrid (B-DPA-PANI@Fe3O4) fillers and epoxy matrix. The results showed most
      significant improvement in corrosion inhibition using electrochemical impedance
      spectroscopy (EIS) in 3.5 wt % NaCl, as well as a significant response in oil
      sensing test. High charge transfer resistance of 110 * 106 Omega.cm2 using 3-wt %
      of filler was noted compared to 0.35 * 106 Omega.cm2 for the pure epoxy. The
      results obtained herein will open new routes for the preparation of efficient
      anticorrosion sensor coatings.

PMID- 30190531
TI  - Hallmarks of cardiac regeneration.

PMID- 30190530
TI  - Dampening of Submesoscale Currents by Air-Sea Stress Coupling in the Californian
      Upwelling System.
AB  - Oceanic submesoscale currents (SMCs) occur on an scale of 0.1-10 km horizontally
      and have a large influence on the oceanic variability and on ecosystems. At the
      mesoscale (10-250 km), oceanic thermal and current feedbacks are known to have a
      significant influence on the atmosphere and on oceanic dynamics. However, air-sea
      interactions at the submesoscale are not well known because the small size of
      SMCs presents observational and simulation barriers. Using high-resolution
      coupled oceanic and atmospheric models for the Central California region during
      the upwelling season, we show that the current feedback acting through the
      surface stress dominates the thermal feedback effect on the ocean and dampens the
      SMC variability by ~17% +/- 4%. As for the mesoscale, the current feedback
      induces an ocean sink of energy at the SMCs and a source of atmospheric energy
      that is related to induced Ekman pumping velocities. However, those additional
      vertical velocities also cause an increase of the injection of energy by
      baroclinic conversion into the SMCs, partially counteracting the sink of energy
      by the stress coupling. These stress coupling effects have important implications
      in understanding SMC variability and its links with the atmosphere and should be
      tested in other regions.

PMID- 30190529
TI  - Differences in antigenic sites and other functional regions between genotype A
      and G mumps virus surface proteins.
AB  - The surface proteins of the mumps virus, the fusion protein (F) and
      haemagglutinin-neuraminidase (HN), are key factors in mumps pathogenesis and are
      important targets for the immune response during mumps virus infection. We
      compared the predicted amino acid sequences of the F and HN genes from Dutch
      mumps virus samples from the pre-vaccine era (1957-1982) with mumps virus
      genotype G strains (from 2004 onwards). Genotype G is the most frequently
      detected mumps genotype in recent outbreaks in vaccinated communities, especially
      in Western Europe, the USA and Japan. Amino acid differences between the Jeryl
      Lynn vaccine strains (genotype A) and genotype G strains were predominantly
      located in known B-cell epitopes and in N-linked glycosylation sites on the HN
      protein. There were eight variable amino acid positions specific to genotype A or
      genotype G sequences in five known B-cell epitopes of the HN protein. These
      differences may account for the reported antigenic differences between Jeryl Lynn
      and genotype G strains. We also found amino acid differences in and near sites on
      the HN protein that have been reported to play a role in mumps virus
      pathogenesis. These differences may contribute to the occurrence of genotype G
      outbreaks in vaccinated communities.

PMID- 30190533
TI  - A Relational Formulation of Quantum Mechanics.
AB  - Non-relativistic quantum mechanics is reformulated here based on the idea that
      relational properties among quantum systems, instead of the independent
      properties of a quantum system, are the most fundamental elements to construct
      quantum mechanics. This idea, combining with the emphasis that measurement of a
      quantum system is a bidirectional interaction process, leads to a new framework
      to calculate the probability of an outcome when measuring a quantum system. In
      this framework, the most basic variable is the relational probability amplitude.
      Probability is calculated as summation of weights from the alternative
      measurement configurations. The properties of quantum systems, such as
      superposition and entanglement, are manifested through the rules of counting the
      alternatives. Wave function and reduced density matrix are derived from the
      relational probability amplitude matrix. They are found to be secondary
      mathematical tools that equivalently describe a quantum system without explicitly
      calling out the reference system. Schrodinger Equation is obtained when there is
      no entanglement in the relational probability amplitude matrix. Feynman Path
      Integral is used to calculate the relational probability amplitude, and is
      further generalized to formulate the reduced density matrix. In essence, quantum
      mechanics is reformulated as a theory that describes physical systems in terms of
      relational properties.

PMID- 30190532
TI  - Quantum nondemolition measurement of mechanical motion quanta.
AB  - The fields of optomechanics and electromechanics have facilitated numerous
      advances in the areas of precision measurement and sensing, ultimately driving
      the studies of mechanical systems into the quantum regime. To date, however, the
      quantization of the mechanical motion and the associated quantum jumps between
      phonon states remains elusive. For optomechanical systems, the coupling to the
      environment was shown to make the detection of the mechanical mode occupation
      difficult, typically requiring the single-photon strong-coupling regime. Here, we
      propose and analyse an electromechanical setup, which allows us to overcome this
      limitation and resolve the energy levels of a mechanical oscillator. We found
      that the heating of the membrane, caused by the interaction with the environment
      and unwanted couplings, can be suppressed for carefully designed
      electromechanical systems. The results suggest that phonon number measurement is
      within reach for modern electromechanical setups.

PMID- 30190534
TI  - Utilization of rare codon-rich markers for screening amino acid overproducers.
AB  - The translation of rare codons relies on their corresponding rare tRNAs, which
      could not be fully charged under amino acid starvation. Theoretically, disrupted
      or retarded translation caused by the lack of charged rare tRNAs can be partially
      restored by feeding or intracellular synthesis of the corresponding amino acids.
      Inspired by this assumption, we develop a screening or selection system for
      obtaining overproducers of a target amino acid by replacing its common codons
      with the corresponding synonymous rare alternative in the coding sequence of
      selected reporter proteins or antibiotic-resistant markers. Results show that
      integration of rare codons can inhibit gene translations in a frequency-dependent
      manner. As a proof-of-concept, Escherichia coli strains overproducing L-leucine,
      L-arginine or L-serine are successfully selected from random mutation libraries.
      The system is also applied to Corynebacterium glutamicum to screen out L-arginine
      overproducers. This strategy sheds new light on obtaining and understanding amino
      acid overproduction strains.

PMID- 30190535
TI  - Low Gilbert Damping Constant in Perpendicularly Magnetized W/CoFeB/MgO Films with
      High Thermal Stability.
AB  - Perpendicular magnetic materials with low damping constant and high thermal
      stability have great potential for realizing high-density, non-volatile, and low
      power consumption spintronic devices, which can sustain operation reliability for
      high processing temperatures. In this work, we study the Gilbert damping constant
      (alpha) of perpendicularly magnetized W/CoFeB/MgO films with a high perpendicular
      magnetic anisotropy (PMA) and superb thermal stability. The alpha of these PMA
      films annealed at different temperatures (Tann) is determined via an all-optical
      Time-Resolved Magneto-Optical Kerr Effect method. We find that alpha of these
      W/CoFeB/MgO PMA films decreases with increasing Tann, reaches a minimum of alpha
      = 0.015 at Tann = 350  degrees C, and then increases to 0.020 after post
      annealing at 400  degrees C. The minimum alpha observed at 350  degrees C is
      rationalized by two competing effects as Tann becomes higher: the enhanced
      crystallization of CoFeB and dead-layer growth occurring at the two interfaces of
      the CoFeB layer. We further demonstrate that alpha of the 400  degrees C-annealed
      W/CoFeB/MgO film is comparable to that of a reference Ta/CoFeB/MgO PMA film
      annealed at 300  degrees C, justifying the enhanced thermal stability of the W
      seeded CoFeB films.

PMID- 30190539
TI  - Author Correction: Genetic markers for urine haptoglobin is associated with
      decline in renal function in type 2 diabetes in East Asians.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has not been fixed in the paper.

PMID- 30190537
TI  - Aluminum plasmonic waveguides co-integrated with Si3N4 photonics using CMOS
      processes.
AB  - Co-integrating CMOS plasmonics and photonics became the "sweet spot" to hit in
      order to combine their benefits and allow for volume manufacturing of plasmo
      photonic integrated circuits. Plasmonics can naturally interface photonics with
      electronics while offering strong mode confinement, enabling in this way on-chip
      data interconnects when tailored to single-mode waveguides, as well as high
      sensitivity biosensors when exposing Surface-Plasmon-Polariton (SPP) modes in
      aqueous environment. Their synergy with low-loss photonics can tolerate the high
      plasmonic propagation losses in interconnect applications, offering at the same
      time a powerful portfolio of passive photonic functions towards avoiding the use
      of bulk optics for SPP excitation and facilitating compact biosensor setups. The
      co-integration roadmap has to proceed, however, over the utilization of fully
      CMOS compatible material platforms and manufacturing processes in order to allow
      for a practical deployment route. Herein, we demonstrate for the first time
      Aluminum plasmonic waveguides co-integrated with Si3N4 photonics using CMOS
      manufacturing processes. We validate the data carrying credentials of CMOS
      plasmonics with 25 Gb/s data traffic and we confirm successful plasmonic
      propagation in both air and water-cladded waveguide configurations. This platform
      can potentially fuel the deployment of co-integrated plasmonic and photonic
      structures using CMOS processes for biosensing and on-chip interconnect
      applications.

PMID- 30190538
TI  - microCLIP super learning framework uncovers functional transcriptome-wide miRNA
      interactions.
AB  - Argonaute crosslinking and immunoprecipitation (CLIP) experiments are the most
      widely used high-throughput methodologies for miRNA targetome characterization.
      The analysis of Photoactivatable Ribonucleoside-Enhanced (PAR) CLIP methodology
      focuses on sequence clusters containing T-to-C conversions. Here, we demonstrate
      for the first time that the non-T-to-C clusters, frequently observed in PAR-CLIP
      experiments, exhibit functional miRNA-binding events and strong RNA
      accessibility. This discovery is based on the analysis of an extensive compendium
      of bona fide miRNA-binding events, and is further supported by numerous miRNA
      perturbation experiments and structural sequencing data. The incorporation of
      these previously neglected clusters yields an average of 14% increase in miRNA
      target interactions per PAR-CLIP library. Our findings are integrated in
      microCLIP ( www.microrna.gr/microCLIP ), a cutting-edge framework that combines
      deep learning classifiers under a super learning scheme. The increased
      performance of microCLIP in CLIP-Seq-guided detection of miRNA interactions,
      uncovers previously elusive regulatory events and miRNA-controlled pathways.

PMID- 30190536
TI  - European dog owner perceptions of obesity and factors associated with human and
      canine obesity.
AB  - Obesity is a common nutrition-related disorder leading to reduced life expectancy
      in both humans and dogs. With the aim of identifying new prevention and control
      options, the study objectives were (1) to investigate dog-owner perceptions about
      obesity in terms of themselves and their dogs, and (2) to identify factors
      associated with obesity and possible social, environmental and economic drivers
      for its development in dog owners and their pets. A cross-sectional questionnaire
      based study was performed across multiple countries. The questionnaire focused on
      human and canine obesity, associated factors and potential drivers, and was
      distributed online and in the form of hard copies among dog owners in 11 European
      countries. In total, 3,185 responses from ten countries were included in
      multivariable analyses. Between 19.1% and 48.8% of the dog owners reported to be
      overweight/obese. Owner-reported overweight/obesity in dogs ranged from 6.0% to
      31.3% based on body condition score charts, and 31.8% to 69.4% based on body fat
      index charts. Common factors associated with obesity in owners and their dogs
      were age, gender and owners' attitudes to diet and physical activity. Dog owners
      who did not consider obesity to be a disease were more likely to have obese dogs.

PMID- 30190540
TI  - Link Prediction based on Quantum-Inspired Ant Colony Optimization.
AB  - Incomplete or partial observations of network structures pose a serious challenge
      to theoretical and engineering studies of real networks. To remedy the missing
      links in real datasets, topology-based link prediction is introduced into the
      studies of various networks. Due to the complexity of network structures, the
      accuracy and robustness of most link prediction algorithms are not satisfying
      enough. In this paper, we propose a quantum-inspired ant colony optimization
      algorithm that integrates ant colony optimization and quantum computing to
      predict links in networks. Extensive experiments on both synthetic and real
      networks show that the accuracy and robustness of the new algorithm is
      competitive in respect to most of the state of the art algorithms. This result
      suggests that the application of intelligent optimization to link prediction is
      promising for boosting its accuracy and robustness.

PMID- 30190541
TI  - Targeted enrichment outperforms other enrichment techniques and enables more
      multi-species RNA-Seq analyses.
AB  - Enrichment methodologies enable the analysis of minor members in multi-species
      transcriptomic data. We compared the standard enrichment of bacterial and
      eukaryotic mRNA to a targeted enrichment using an Agilent SureSelect (AgSS)
      capture for Brugia malayi, Aspergillus fumigatus, and the Wolbachia endosymbiont
      of B. malayi (wBm). Without introducing significant systematic bias, the AgSS
      quantitatively enriched samples, resulting in more reads mapping to the target
      organism. The AgSS-enriched libraries consistently had a positive linear
      correlation with their unenriched counterparts (r2 = 0.559-0.867). Up to a 2,242
      fold enrichment of RNA from the target organism was obtained following a power
      law (r2 = 0.90), with the greatest fold enrichment achieved in samples with the
      largest ratio difference between the major and minor members. While using a
      single total library for prokaryote and eukaryote enrichment from a single RNA
      sample could be beneficial for samples where RNA is limiting, we observed a
      decrease in reads mapping to protein coding genes and an increase in multi
      mapping reads to rRNAs in AgSS enrichments from eukaryotic total RNA libraries
      compared to eukaryotic poly(A)-enriched libraries. Our results support a
      recommendation of using AgSS targeted enrichment on poly(A)-enriched libraries
      for eukaryotic captures, and total RNA libraries for prokaryotic captures, to
      increase the robustness of multi-species transcriptomic studies.

PMID- 30190542
TI  - Evaluation of alpha-II-spectrin breakdown products as potential biomarkers for
      early recognition and severity of aneurysmal subarachnoid hemorrhage.
AB  - This study assessed whether cytoskeletal protein alpha-II spectrin breakdown
      products (SBDP150, SBDP145, and SBDP120) would identify the presence of aSAH and
      be associated with severity (GCS score, WFNS grade and survival to hospital
      discharge). This prospective case-control study, conducted at a tertiary care
      Level I trauma center, enrolled adult patients with angiography confirmed aSAH
      who underwent ventriculostomy placement for cerebrospinal fluid (CSF) drainage.
      There were 40 patients enrolled in the study, 20 with aSAH and 20 control
      subjects. Patients with aSAH were a mean age of 54 (SD15) and 75% were female.
      There were significant differences in SBDP150, SBDP145, and SBDP120 CSF levels
      between patients with and without aSAH (p < 0.001), even in those presenting with
      a GCS Score of 15 and a WFNS Grade 1. The AUC for distinguishing aSAH from
      control subjects was 1.0 for SBDP150 and SBDP145, and 0.95 for SBDP120. SBDP150
      and SBDP145 both yielded sensitivities and specificities of 100% and SBDP120 was
      90% and 100% respectively. Moreover, there were significantly higher levels of
      SBDP150 and SBDP145 in the non-survivors than in the survivors (p < 0.001). This
      study demonstrates the potential that SBDP's have as biomarkers for recognition
      and severity of aSAH. A larger prospective study is warranted.

PMID- 30190543
TI  - EEG patterns of self-paced movement imaginations towards externally-cued and
      internally-selected targets.
AB  - In this study, we investigate the neurophysiological signature of the interacting
      processes which lead to a single reach-and-grasp movement imagination (MI). While
      performing this task, the human healthy participants could either define their
      movement targets according to an external cue, or through an internal selection
      process. After defining their target, they could start the MI whenever they
      wanted. We recorded high density electroencephalographic (EEG) activity and
      investigated two neural correlates: the event-related potentials (ERPs)
      associated with the target selection, which reflect the perceptual and cognitive
      processes prior to the MI, and the movement-related cortical potentials (MRCPs),
      associated with the planning of the self-paced MI. We found differences in
      frontal and parietal areas between the late ERP components related to the
      internally-driven selection and the externally-cued process. Furthermore, we
      could reliably estimate the MI onset of the self-paced task. Next, we extracted
      MRCP features around the MI onset to train classifiers of movement vs. rest
      directly on self-paced MI data. We attained performance significantly higher than
      chance level for both time-locked and asynchronous classification. These findings
      contribute to the development of more intuitive brain-computer interfaces in
      which movement targets are defined internally and the movements are self-paced.

PMID- 30190544
TI  - Association of short-term exposure to ambient carbon monoxide with hospital
      admissions in China.
AB  - Evidence on the acute effects of ambient carbon monoxide (CO) pollution on
      morbidity risk in developing countries is scarce and inconsistent. We conducted a
      multicity case-crossover study in 26 largest cities in China from January, 2014
      to December, 2015 to examine the association between short-term exposure to CO
      and daily hospital admission. We fitted conditional logistic regression to obtain
      effect estimates of the associations. We also performed subset analyses to
      explore the health effects of CO at low levels. During the study period, a total
      of 14,569,622, 2,008,786 and 916,388 all-cause, cardiovascular and respiratory
      admissions were identified, respectively. A 1 mg/m3 increase in the CO
      concentrations corresponded to a 3.75% (95% CI, 3.63-3.87%), 4.39% (95% CI, 4.07
      4.70%), and 4.44% (95% CI, 3.97-4.92%) increase in all-cause, cardiovascular, and
      respiratory admissions on the same day, respectively. The associations were
      robust to controlling for criteria co-pollutants. In subset analyses, negative
      effects of short-term CO exposure on hospital admission were observed at lower
      concentrations (<1 mg/m3), while positive effects were observed at higher
      concentrations (>2 mg/m3). In conclusion, current CO levels in China were
      significantly associated with increased daily hospital admissions.

PMID- 30190545
TI  - Role of SUMOylation in differential ERalpha transcriptional repression by
      tamoxifen and fulvestrant in breast cancer cells.
AB  - Antiestrogens (AEs) are widely used for treatment of estrogen receptor alpha
      (ERalpha)-positive breast cancer, but display variable degrees of partial agonism
      in estrogen target tissues and breast cancer (BC) cells. The fact that BC cells
      resistant to selective ER modulators (SERMs) like tamoxifen (Tam) can still be
      sensitive to pure AEs, also called selective ER downregulators, suggests
      different mechanisms of action, some of which may contribute to the more complete
      suppression of estrogen target genes by pure AEs. We report herein that pure AEs
      such as fulvestrant induce transient binding of ERalpha to DNA, followed by rapid
      release after 30-40 min without loss of nuclear localization. Loss of DNA binding
      preceded receptor degradation and was not prevented by proteasome inhibition.
      Chromatin was less accessible in the presence of fulvestrant than with estradiol
      or Tam as early as 20 min following treatment, suggesting that chromatin
      remodeling by pure AEs at ERalpha target regions prevents transcription in spite
      of receptor binding. SUMO2/3 marks were detected on chromatin at the peak of
      ERalpha binding in cells treated with pure AEs, but not SERMs. Furthermore,
      decreasing SUMOylation by overexpressing the deSUMOylase SENP1 significantly
      delayed receptor release from DNA and de-repressed expression of estrogen target
      genes in the presence of fulvestrant, both in ERalpha-expressing MCF-7 cells and
      in transiently transfected ER-negative SK-BR-3 cells. Finally, mutation V534E,
      identified in a breast metastasis resistant to hormonal therapies, prevented
      ERalpha modification and resulted in increased transcriptional activity of
      estrogen target genes in the presence of fulvestrant in SK-BR-3 cells. Together,
      our results establish a role for SUMOylation in achieving a more complete
      transcriptional shut-off of estrogen target genes by pure AEs vs. SERMs in BC
      cells.

PMID- 30190546
TI  - Premature activation of Cdk1 leads to mitotic events in S phase and embryonic
      lethality.
AB  - Cell cycle regulation, especially faithful DNA replication and mitosis, are
      crucial to maintain genome stability. Cyclin-dependent kinase (CDK)/cyclin
      complexes drive most processes in cellular proliferation. In response to DNA
      damage, cell cycle surveillance mechanisms enable normal cells to arrest and
      undergo repair processes. Perturbations in genomic stability can lead to tumor
      development and suggest that cell cycle regulators could be effective targets in
      anticancer therapy. However, many clinical trials ended in failure due to off
      target effects of the inhibitors used. Here, we investigate in vivo the
      importance of WEE1- and MYT1-dependent inhibitory phosphorylation of mammalian
      CDK1. We generated Cdk1AF knockin mice, in which two inhibitory phosphorylation
      sites are replaced by the non-phosphorylatable amino acids T14A/Y15F. We
      uncovered that monoallelic expression of CDK1AF is early embryonic lethal in mice
      and induces S phase arrest accompanied by gammaH2AX and DNA damage checkpoint
      activation in mouse embryonic fibroblasts (MEFs). The chromosomal fragmentation
      in Cdk1AF MEFs does not rely on CDK2 and is partly caused by premature activation
      of MUS81-SLX4 structure-specific endonuclease complexes, as well as untimely
      onset of chromosome condensation followed by nuclear lamina disassembly. We
      provide evidence that tumor development in liver expressing CDK1AF is inhibited.
      Interestingly, the regulatory mechanisms that impede cell proliferation in CDK1AF
      expressing cells differ partially from the actions of the WEE1 inhibitor, MK
      1775, with p53 expression determining the sensitivity of cells to the drug
      response. Thus, our work highlights the importance of improved therapeutic
      strategies for patients with various cancer types and may explain why some
      patients respond better to WEE1 inhibitors.

PMID- 30190547
TI  - Time-advanced occurrence of moderate-size earthquakes in a stable intraplate
      region after a megathrust earthquake and their seismic properties.
AB  - The distance-dependent coseismic and postseismic displacements produced by the
      2011 MW9.0 Tohoku-Oki megathrust earthquake caused medium weakening and stress
      perturbation in the crust around the Korean Peninsula, increasing the seismicity
      with successive ML5-level earthquakes at the outskirts of high seismicity
      regions. The average ML5-level occurrence rate prior to the megathrust earthquake
      was 0.15 yr-1 (0.05-0.35 yr-1 at a 95% confidence level), and the rate has
      increased to 0.71 yr-1 (0.23-1.67 yr-1 at a 95% confidence level) since the
      megathrust earthquake. The 2016 ML5-level midcrustal earthquakes additionally
      changed the stress field in adjacent regions, inducing the 15 November 2017 ML5.4
      earthquake. The successive 2016 and 2017 moderate-size earthquakes built complex
      stress fields in the southeastern Korean Peninsula, increasing the seismic hazard
      risks in the regions of long-term stress accumulation. The increased seismic
      risks may continue until the medium properties and stress field are recovered.

PMID- 30190549
TI  - Patient outcomes following implantation with a trifocal toric IOL: twelve-month
      prospective multicentre study.
AB  - PURPOSE: To evaluate clinical outcomes with a premium diffractive-refractive
      trifocal toric intraocular lens (IOL) over a 12-month period. METHODS:
      Multicentre prospective clinical trial including 227 eyes of 114 patients
      undergoing cataract surgery with bilateral implantation of the AT LISA tri toric
      939MP IOL (Carl Zeiss Meditec, Jena, Germany). One patient was implanted
      unilaterally. Outcome measures were: visual acuity, manifest refraction, reading
      performance, contrast sensitivity, defocus curve, patient satisfaction and
      subjective quality of vision. Alpins vector analysis was used to evaluate
      astigmatic changes. RESULTS: 12-month follow up results of binocular uncorrected
      distance, intermediate and near visual acuity were <=0.3 logMAR in 99.0%, 98.10%
      and 91.40% of eyes, respectively. 79.7% of eyes had a cylinder value of +/-0.50 D
      at 12 months post-surgery. Contrast sensitivity was in the normal range at 6
      months post-surgery. The defocus curve exhibited a smooth transition between far
      and near foci. Vector analysis showed a mean magnitude of error of -0.16 +/- 0.48
      D. Mean binocular distance-corrected reading visual acuity was 0.15 +/- 0.13
      logRAD at 6 months postoperatively. 93.3%, 89.4% and 84.6% of patients expressed
      satisfaction (good or very good) with distance, intermediate and near vision,
      respectively, 12 months after surgery. Most (>=95%) patients felt that visual
      disturbances, including halos, glare, focusing difficulties and depth perception,
      caused little or no disturbance. CONCLUSIONS: The diffractive-refractive trifocal
      toric IOL, AT LISA tri toric 939MP, provides effective distance, intermediate and
      near visual acuity in eyes with corneal astigmatism. Patient satisfaction was
      high and 98.1% of patients expressed satisfaction with the IOL implanted.

PMID- 30190551
TI  - Fit-free analysis of fluorescence lifetime imaging data using the phasor
      approach.
AB  - Fluorescence lifetime imaging microscopy (FLIM) is used in diverse disciplines,
      including biology, chemistry and biophysics, but its use has been limited by the
      complexity of the data analysis. The phasor approach to FLIM has the potential to
      markedly reduce this complexity and at the same time provide a powerful
      visualization of the data content. Phasor plots for fluorescence lifetime
      analysis were originally developed as a graphical representation of excited-state
      fluorescence lifetimes for in vitro systems. The method's simple mathematics and
      specific rules avoid errors and confusion common in the study of complex and
      heterogeneous fluorescence. In the case of FLIM, the phasor approach has become a
      powerful method for simple and fit-free analyses of the information contained in
      the many thousands of pixels constituting an image. At present, the phasor plot
      is used not only for FLIM, but also for hyperspectral imaging, wherein phasors
      provide an unprecedented understanding of heterogeneous fluorescence.
      Undoubtedly, phasor plots will be increasingly important in the future analysis
      and understanding of FLIM and hyperspectral confocal imaging. This protocol
      presents the principle of the method and guides users through one of the popular
      interfaces for FLIM phasor analysis, namely, the SimFCS software. Implementation
      of the analysis takes only minutes to complete for a dataset containing hundreds
      of files.

PMID- 30190550
TI  - Accessing crystal-crystal interaction forces with oriented nanocrystal atomic
      force microscopy probes.
AB  - Biominerals serve as critical structures of living systems and play important
      roles in biochemical processes. Understanding their crystallization mechanisms is
      therefore central to many areas of biology, biogeoscience, and biochemistry. Some
      biominerals, such as bone and dentin, are hierarchical nanocomposite structures
      constructed by sequential addition of individual oriented nanocrystals. The
      driving forces that enable this oriented assembly are still poorly understood,
      with advances in understanding limited in part by the availability of techniques
      that can precisely measure the delicate interactions between nanocrystals as a
      function of their separation distance and mutual orientation. Here, we provide a
      comprehensive protocol for (i) fabricating oriented single-nanocrystal atomic
      force microscopy (AFM) probes using focused ion beam (FIB) milling and (ii)
      performing oriented nanocrystal interaction force measurements using dynamic
      force spectroscopy (DFS)-based AFM and environmental transmission electron
      microscopy (ETEM)-AFM techniques. We illustrate how to fabricate oriented
      nanocrystal force probes using commercial bulk crystals or nano/microcrystals of
      calcite, zinc oxide, and rutile. The typical protocol for fabricating one AFM
      crystal probe takes 2-3 h. In addition, we illustrate how to quantify the
      direction-specific interaction forces for a given pair of interacting oriented
      nanocrystal faces. The methods are fully transferrable to other minerals of
      interest, such as the apatites constituting bone minerals. This allows
      researchers across many fields to measure and understand particle-based
      crystallization processes.

PMID- 30190548
TI  - Prediction of Gestational Diabetes Mellitus and Pre-diabetes 5 Years Postpartum
      using 75 g Oral Glucose Tolerance Test at 14-16 Weeks' Gestation.
AB  - Early detection and treatment of women at risk for gestational diabetes mellitus
      (GDM) could improve perinatal and long-term outcomes in GDM women and their
      offspring. We explored if a 75 g oral glucose tolerance test (OGTT) at 14-16
      weeks of gestation could identify women who will (1) develop GDM or give birth to
      large-for-gestational-age (LGA) babies in 1031 pregnant women from the STORK
      study using different diagnostic criteria (WHO1999, IADPSG2010, WHO2013,
      NORWAY2017) and (2) develop pre-diabetes 5 years postpartum focusing on first
      trimester beta-cell function in a separate study of 300 women from the STORK
      cohort. The sensitivity of the 14-16 week OGTT to identify women who would
      develop GDM or have LGA babies was low, and we could not identify alternative cut
      offs to exclude women not at risk or identify women that could benefit from early
      intervention. First trimester beta-cell function was a stronger determinant than
      third trimester beta-cell function of predicting maternal pre-diabetes. In
      conclusion, in our normal low-risk population, the 75 g OGTT at 14-16 weeks is
      insufficient to identify candidates for early treatment of GDM or identify women
      not likely to develop GDM or have LGA babies. First trimester beta-cell function
      may predict pre-diabetes 5 years postpartum.

PMID- 30190552
TI  - Preparation of asymmetric phospholipid vesicles for use as cell membrane models.
AB  - Freely suspended liposomes are widely used as model membranes for studying lipid
      lipid and protein-lipid interactions. Liposomes prepared by conventional methods
      have chemically identical bilayer leaflets. By contrast, living cells actively
      maintain different lipid compositions in the two leaflets of the plasma membrane,
      resulting in asymmetric membrane properties that are critical for normal cell
      function. Here, we present a protocol for the preparation of unilamellar
      asymmetric phospholipid vesicles that better mimic biological membranes.
      Asymmetry is generated by methyl-beta-cyclodextrin-catalyzed exchange of the
      outer leaflet lipids between vesicle pools of differing lipid composition. Lipid
      destined for the outer leaflet of the asymmetric vesicles is provided by heavy
      donor multilamellar vesicles containing a dense sucrose core. Donor lipid is
      exchanged into extruded unilamellar acceptor vesicles that lack the sucrose core,
      facilitating the post-exchange separation of the donor and acceptor pools by
      centrifugation because of differences in vesicle size and density. We present two
      complementary assays allowing quantification of each leaflet's lipid composition:
      the overall lipid composition is determined by gas chromatography-mass
      spectrometry, whereas the lipid distribution between the two leaflets is
      determined by NMR, using the lanthanide shift reagent Pr3+. The preparation
      protocol and the chromatographic assay can be applied to any type of phospholipid
      bilayer, whereas the NMR assay is specific to lipids with choline-containing
      headgroups, such as phosphatidylcholine and sphingomyelin. In ~12 h, the protocol
      can produce a large yield of asymmetric vesicles (up to 20 mg) suitable for a
      wide range of biophysical studies.

PMID- 30190553
TI  - PhIP-Seq characterization of serum antibodies using oligonucleotide-encoded
      peptidomes.
AB  - The binding specificities of an individual's antibody repertoire contain a wealth
      of biological information. They harbor evidence of environmental exposures,
      allergies, ongoing or emerging autoimmune disease processes, and responses to
      immunomodulatory therapies, for example. Highly multiplexed methods to
      comprehensively interrogate antibody-binding specificities have therefore emerged
      in recent years as important molecular tools. Here, we provide a detailed
      protocol for performing 'phage immunoprecipitation sequencing' (PhIP-Seq), which
      is a powerful method for analyzing antibody-repertoire binding specificities with
      high throughput and at low cost. The methodology uses oligonucleotide library
      synthesis (OLS) to encode proteomic-scale peptide libraries for display on
      bacteriophage. These libraries are then immunoprecipitated, using an individual's
      antibodies, for subsequent analysis by high-throughput DNA sequencing. We have
      used PhIP-Seq to identify novel self-antigens associated with autoimmune disease,
      to characterize the self-reactivity of broadly neutralizing HIV antibodies, and
      in a large international cross-sectional study of exposure to hundreds of human
      viruses. Compared with alternative array-based techniques, PhIP-Seq is far more
      scalable in terms of sample throughput and cost per analysis. Cloning and
      expression of recombinant proteins are not required (versus protein microarrays),
      and peptide lengths are limited only by DNA synthesis chemistry (up to 90-aa
      (amino acid) peptides versus the typical 8- to 12-aa length limit of synthetic
      peptide arrays). Compared with protein microarrays, however, PhIP-Seq libraries
      lack discontinuous epitopes and post-translational modifications. To increase the
      accessibility of PhIP-Seq, we provide detailed instructions for the design of
      phage-displayed peptidome libraries, their immunoprecipitation using serum
      antibodies, deep sequencing-based measurement of peptide abundances, and
      statistical determination of peptide enrichments that reflect antibody-peptide
      interactions. Once a library has been constructed, PhIP-Seq data can be obtained
      for analysis within a week.

PMID- 30190554
TI  - A three-dimensional engineered heterogeneous tumor model for assessing cellular
      environment and response.
AB  - This protocol describes how to build and implement a three-dimensional (3D) cell
      culture system, TRACER (tissue roll for analysis of cellular environment and
      response), that enables analysis of cellular behavior and phenotype in hypoxic
      gradients. TRACER consists of infiltrating cells encapsulated in a hydrogel
      extracellular matrix (ECM) within a thin strip of porous cellulose scaffolding
      that is then rolled around an oxygen-impermeable mandrel for assembly of thick
      and layered 3D tissue constructs that develop cell-defined oxygen gradients.
      TRACER differs from other stacked-paper cell culture models because it is
      assembled from a single-piece scaffold, which facilitates rapid disassembly for
      analysis of different cell populations and metabolites. The protocol describes
      how to fabricate TRACER components, cell seeding in the scaffold, and scaffold
      assembly and disassembly. Furthermore, it provides methods to quantify live,
      dead, or proliferating cells, as well as gradients of oxygen using the
      nitroimidazole derivative EF5, in a layer-by-layer analysis with confocal
      microscopy or by flow cytometry of cells isolated from the TRACER scaffold.
      Additional methods to isolate live cells from TRACER layers for dose-response
      analysis with a clonogenic assay, as well as steps to extract RNA or fast
      changing metabolites from TRACER layers, are also presented. Finally, we provide
      alternative steps to establish TRACER co-cultures for assessment of tumor cell
      invasion and metastasis, in this case in the absence of a hypoxic gradient.
      Although analysis time varies according to the assay chosen, scaffold fabrication
      and seeding typically take 2 h, and TRACER assembly takes 20 min on the day
      following scaffold seeding. The TRACER platform is designed for use by
      researchers and students who have basic tissue culture experience.

PMID- 30190555
TI  - High-throughput and high-sensitivity phosphoproteomics with the EasyPhos
      platform.
AB  - Mass spectrometry has transformed the field of cell signaling by enabling global
      studies of dynamic protein phosphorylation ('phosphoproteomics'). Recent
      developments are enabling increasingly sophisticated phosphoproteomics studies,
      but practical challenges remain. The EasyPhos workflow addresses these and is
      sufficiently streamlined to enable the analysis of hundreds of phosphoproteomes
      at a depth of >10,000 quantified phosphorylation sites. Here we present a
      detailed and updated workflow that further ensures high performance in sample
      limited conditions while also reducing sample preparation time. By eliminating
      protein precipitation steps and performing the entire protocol, including
      digestion, in a single 96-well plate, we now greatly minimize opportunities for
      sample loss and variability. This results in very high reproducibility and a
      small sample size requirement (<=200 MUg of protein starting material). After
      cell culture or tissue collection, the protocol takes 1 d, whereas mass
      spectrometry measurements require ~1 h per sample. Applied to glioblastoma cells
      acutely treated with epidermal growth factor (EGF), EasyPhos quantified 20,132
      distinct phosphopeptides from 200 MUg of protein in less than 1 d of measurement
      time, revealing thousands of EGF-regulated phosphorylation events.

PMID- 30190556
TI  - Configuration of electrical spinal cord stimulation through real-time processing
      of gait kinematics.
AB  - Epidural electrical stimulation (EES) of the spinal cord and real-time processing
      of gait kinematics are powerful methods for the study of locomotion and the
      improvement of motor control after injury or in neurological disorders. Here, we
      describe equipment and surgical procedures that can be used to acquire chronic
      electromyographic (EMG) recordings from leg muscles and to implant targeted
      spinal cord stimulation systems that remain stable up to several months after
      implantation in rats and nonhuman primates. We also detail how to exploit these
      implants to configure electrical spinal cord stimulation policies that allow
      control over the degree of extension and flexion of each leg during locomotion.
      This protocol uses real-time processing of gait kinematics and locomotor
      performance, and can be configured within a few days. Once configured,
      stimulation bursts are delivered over specific spinal cord locations with precise
      timing that reproduces the natural spatiotemporal activation of motoneurons
      during locomotion. These protocols can also be easily adapted for the safe
      implantation of systems in the vicinity of the spinal cord and to conduct
      experiments involving real-time movement feedback and closed-loop controllers.

PMID- 30190557
TI  - PEG-4MAL hydrogels for human organoid generation, culture, and in vivo delivery.
AB  - In vitro differentiation of human pluripotent stem cell (hPSC)-derived organoids
      (HOs) facilitates the production of multicellular three-dimensional structures
      analogous to native human tissues. Most current methods for the generation of HOs
      rely on Matrigel, a poorly defined basement membrane derivative secreted by
      Engelbreth-Holm-Swarm mouse sarcoma cells, limiting the potential use of HOs for
      regenerative medicine applications. Here, we describe a protocol for the
      synthesis of a fully defined, synthetic hydrogel that supports the generation and
      culture of HOs. Modular, cell-encapsulating hydrogels are formed from a four
      armed poly(ethylene glycol) macromer that has maleimide groups at each terminus
      (PEG-4MAL) and is conjugated to cysteine-containing adhesive peptides and cross
      linked via protease-degradable peptides. The protocol also includes guidelines
      for the localized in vivo delivery of PEG-4MAL hydrogel-encapsulated HOs to
      injured mouse colon. The PEG-4MAL hydrogel supports the engraftment of the HOs
      and accelerates colonic wound repair. This culture and delivery strategy can thus
      be used to develop HO-based therapies to treat injury and disease. Hydrogel and
      tissue preparation and subsequent encapsulation can be performed within 2.5-3.5
      h. Once HOs have been cultured in synthetic hydrogels for at least 14 d, they can
      be prepared and delivered to the mouse colon in under 5 h.

PMID- 30190559
TI  - Correction : Characterization of hybridization within a secondary contact region
      of the inshore fish, Bostrychus sinensis, in the East China Sea.
AB  - Following the publication of this article, the authors have requested that the
      Acknowledgements section be amended to thank Weidi Yang for his assistance with
      their Bostrychus sinensis photograph that was chosen for the front cover of the
      January 2018 issue of the journal. This error has been corrected in both the PDF
      and HTML versions of the paper. Also, the legends for Supplementary Figures 1 and
      2 were not posted online. This error has been corrected in the HTML version of
      the paper.

PMID- 30190558
TI  - The emerging sub-genotype C2 of CoxsackievirusA10 Associated with Hand, Foot and
      Mouth Disease extensively circulating in mainland of China.
AB  - Coxsackievirus A10 (CV-A10) associated with Hand, foot, and mouth disease (HFMD)
      cases emerged increasingly in recent years. In this study, the samples from
      nation-wide HFMD surveillance, including 27 out of 31 provinces in China were
      investigated, and the continuous and extensive virological surveillance, covered
      13 years, were conducted to provide a comprehensive molecular characterization
      analysis of CV-A10. 855 CV-A10 viruses (33 severe cases included), were isolated
      from HFMD children patients during 2009 to 2016 in China. 164 representative
      sequences from these viruses, together with 117 CV-A10 sequences downloaded from
      GenBank based on entire VP1 were recruited in this study. Two new genotypes (F
      and G) and two sub-genotypes (C1 and C2) were identified. Among 264 Chinese
      sequences, 9 of them were genotype B, 8 of them were C1, and the other (247) were
      C2, the predominant sub-genotype in China since 2012. Chinese C2 viruses showed
      obvious temporal characteristics and can be divided into 3 clusters (cluster
      1~3). Cluster 3 viruses was circulating extensively during 2014 and 2016 with
      more severe cases. It is very necessary and important to continuously conduct the
      extensive virological surveillance for CV-A10, and further evolutionary studies
      will provide more evidence on its evolution and virulence.

PMID- 30190560
TI  - Power law fitness landscapes and their ability to predict fitness.
AB  - Whether or not evolution by natural selection is predictable depends on the
      existence of general patterns shaping the way mutations interact with the genetic
      background. This interaction, also known as epistasis, has been observed during
      adaptation (macroscopic epistasis) and in individual mutations (microscopic
      epistasis). Interestingly, a consistent negative correlation between the fitness
      effect of beneficial mutations and background fitness (known as diminishing
      returns epistasis) has been observed across different species and conditions. We
      tested whether the adaptation pattern of an additional species,
      Schizosaccharomyces pombe, followed the same trend. We used strains that differed
      by the presence of large karyotype differences and observed the same pattern of
      fitness convergence. Using these data along with published datasets, we measured
      the ability of different models to describe adaptation rates. We found that a
      phenotype-fitness landscape shaped like a power law is able to correctly predict
      adaptation dynamics in a variety of species and conditions. Furthermore we show
      that this model can provide a link between the observed macroscopic and
      microscopic epistasis. It may be very useful in the development of algorithms
      able to predict the adaptation of microorganisms from measures of the current
      phenotypes. Overall, our results suggest that even though adaptation quickly
      slows down, populations adapting to lab conditions may be quite far from a
      fitness peak.

PMID- 30190561
TI  - Environmental pleiotropy and demographic history direct adaptation under
      antibiotic selection.
AB  - Evolutionary rescue following environmental change requires mutations permitting
      population growth in the new environment. If change is severe enough to prevent
      most of the population reproducing, rescue becomes reliant on mutations already
      present. If change is sustained, the fitness effects in both environments, and
      how they are associated-termed 'environmental pleiotropy'-may determine which
      alleles are ultimately favoured. A population's demographic history-its size over
      time-influences the variation present. Although demographic history is known to
      affect the probability of evolutionary rescue, how it interacts with
      environmental pleiotropy during severe and sustained environmental change remains
      unexplored. Here, we demonstrate how these factors interact during antibiotic
      resistance evolution, a key example of evolutionary rescue fuelled by pre
      existing mutations with pleiotropic fitness effects. We combine published data
      with novel simulations to characterise environmental pleiotropy and its effects
      on resistance evolution under different demographic histories. Comparisons among
      resistance alleles typically revealed no correlation for fitness-i.e., neutral
      pleiotropy-above and below the sensitive strain's minimum inhibitory
      concentration. Resistance allele frequency following experimental evolution
      showed opposing correlations with their fitness effects in the presence and
      absence of antibiotic. Simulations demonstrated that effects of environmental
      pleiotropy on allele frequencies depended on demographic history. At the
      population level, the major influence of environmental pleiotropy was on mean
      fitness, rather than the probability of evolutionary rescue or diversity. Our
      work suggests that determining both environmental pleiotropy and demographic
      history is critical for predicting resistance evolution, and we discuss the
      practicalities of this during in vivo evolution.

PMID- 30190562
TI  - Posterior Chamber Phakic Intraocular Lens Implantation in Eyes with an Anterior
      Chamber Depth of Less Than 3 mm: A Multicenter Study.
AB  - This study was aimed to assess the clinical outcomes of Visian ICL (hole ICL;
      STAAR Surgical, Inc.) implantation for the correction of myopic refractive errors
      in eyes having an anterior chamber depth (ACD) below the current manufacturer's
      recommendation (<3.0 mm). We comprised 365 eyes of 201 consecutive patients (mean
      age +/- standard deviation, 35.7 +/- 7.5 years) with spherical equivalents of 
      8.66 +/- 3.54 D. We evaluated the safety, efficacy, predictability, stability,
      intraocular pressure (IOP), endothelial cell density (ECD), and complications.
      The safety and efficacy indices were 1.12 +/- 0.22 and 0.98 +/- 0.22. At 1 year,
      90% and 98% of eyes were within +/- 0.5 and 1.0 D of the attempted correction,
      respectively. Changes in the manifest refraction from 1 week to 1 year
      postoperatively were -0.08 +/- 0.34 D. The mean ECD loss was 0.2 +/- 8.7%. No
      eyes showed a significant ECD loss (>=30%). We found no significant correlation
      between the ACD and the change in ECD (Pearson correlation coefficient r = 
      0.048, p = 0.360). No significant IOP rise or vision-threatening complication
      occurred at any time. These findings indicate that the surgical indication of ICL
      implantation should be reconsidered in terms of ACD.

PMID- 30190563
TI  - Induction chemotherapy followed by concurrent chemoradiotherapy is benefit for
      advanced stage nasopharyngeal carcinoma with different nonkeratinizing carcinoma
      subtypes.
AB  - Given the potentially distinctive histological variations in northwest of China,
      the aim of current study was to compare the efficacy of induction chemotherapy
      plus concurrent chemoradiotherapy (IC + CCRT) with concurrent chemoradiotherapy
      (CCRT) in nasopharyngeal carcinoma (NPC) patients with different histological
      types. A total of 301 patients were included in this study. Patients were
      classified in two cohorts according to the 2005 WHO World Health Organization
      histological classification: WHO type IIa group and WHO type IIb group. The
      Kaplan-Meier method was used to detect the efficacy between IC + CCRT and CCRT in
      two WHO types cohorts. Propensity score matching method was adopted to balance
      the baseline covariate and eliminate potential selection bias. On propensity
      matched analyses, IC + CCRT was found to produce better 3-year DMFS and OS than
      CCRT in WHO type IIa cohort (DMFS, 76.2% vs. 42.2%, p = 0.029; OS, 78.3% vs.
      65.5%, p = 0.027). For WHO type IIb cohort, IC + CCRT was associated with a
      better 3-year OS (87.4% vs. 77.9%, p = 0.029) and a trend of better 3-year DMFS
      (85.9% vs. 76%, p = 0.162) compared with CCRT. IC + CCRT was benefit for advanced
      stage nasopharyngeal carcinoma with different nonkeratinizing carcinoma subtypes.

PMID- 30190564
TI  - Habitat environments impacted the gut microbiome of long-distance migratory swan
      geese but central species conserved.
AB  - The gut microbime plays an important role in the health of wild animals. This
      microbial community could be altered by habitat pollution and other human
      activities that threaten the host organisms. Here, we satellite-tracked a flock
      of swan geese (Anser cygnoides) migrating from their breeding area (Khukh Lake,
      Mongolia), with low levels of human activity, to their wintering area (Poyang
      Lake, China) which has been heavily impacted by human activities. Twenty fecal
      samples were collected from each site. High-throughput sequencing of 16S and ITS
      was employed to explore bacterial and fungal composition and diversity of their
      gut microbiome. Although general composition, alpha-diversity, functional
      prediction, and the central taxa in the phylogenetic networks showed some
      similarities between the two habitats, significant divergences were detected in
      terms of beta-diversity, species abundances, and interaction network topologies.
      In addition, disease-related and xenobiotic biodegradation pathways, and
      pathogenic bacteria were significantly increased in bacterial communities from
      samples at Poyang Lake. Our results reveal that the gut microbiome of swan geese,
      while somewhat altered after long-distance migration, still maintained a core
      group of species. We also show that habitat environmental stress could impact
      these gut microbial communities, suggesting that habitat pollution could
      indirectly threaten wild animals by altering their gut microbiome.

PMID- 30190566
TI  - Genomic analysis reveals genes affecting distinct phenotypes among different
      Chinese and western pig breeds.
AB  - The differences in artificial and natural selection have been some of the factors
      contributing to phenotypic diversity between Chinese and western pigs. Here, 830
      individuals from western and Chinese pig breeds were genotyped using the reduced
      representation genotyping method. First, we identified the selection signatures
      for different pig breeds. By comparing Chinese pigs and western pigs along the
      first principal component, the growth gene IGF1R; the immune genes IL1R1, IL1RL1,
      DUSP10, RAC3 and SWAP70; the meat quality-related gene SNORA50 and the olfactory
      gene OR1F1 were identified as candidate differentiated targets. Further, along a
      principal component separating Pudong White pigs from others, a potential causal
      gene for coat colour (EDNRB) was discovered. In addition, the divergent
      signatures evaluated by Fst within Chinese pig breeds found genes associated with
      the phenotypic features of coat colour, meat quality and feed efficiency among
      these indigenous pigs. Second, admixture and genomic introgression analysis were
      performed. Shan pigs have introgressed genes from Berkshire, Yorkshire and
      Hongdenglong pigs. The results of introgression mapping showed that this
      introgression conferred adaption to the local environment and coat colour of
      Chinese pigs and the superior productivity of western pigs.

PMID- 30190565
TI  - An RNA toolbox for cancer immunotherapy.
AB  - Cancer immunotherapy has revolutionized oncology practice. However, current
      protein and cell therapy tools used in cancer immunotherapy are far from perfect,
      and there is room for improvement regarding their efficacy and safety. RNA-based
      structures have diverse functions, ranging from gene expression and gene
      regulation to pro-inflammatory effects and the ability to specifically bind
      different molecules. These functions make them versatile tools that may advance
      cancer vaccines and immunomodulation, surpassing existing approaches. These
      technologies should not be considered as competitors of current immunotherapies
      but as partners in synergistic combinations and as a clear opportunity to reach
      more efficient and personalized results. RNA and RNA derivatives can be exploited
      therapeutically as a platform to encode protein sequences, provide innate pro
      inflammatory signals to the immune system (such as those denoting viral
      infection), control the expression of other RNAs (including key immunosuppressive
      factors) post-transcriptionally and conform structural scaffoldings binding
      proteins that control immune cells by modifying their function. Nascent RNA
      immunotherapeutics include RNA vaccines encoding cancer neoantigens, mRNAs
      encoding immunomodulatory factors, viral RNA analogues, interference RNAs and
      protein-binding RNA aptamers. These approaches are already in early clinical
      development with promising safety and efficacy results.

PMID- 30190568
TI  - Metallo supramolecular cylinders inhibit HIV-1 TAR-TAT complex formation and
      viral replication in cellulo.
AB  - Shape-selective recognition of nucleic acid structures by supramolecular drugs
      offers the potential to treat disease. The Trans Activation Response (TAR) region
      is a region of high secondary structure within the human immunodeficiency virus-1
      (HIV-1) RNA that complexes with the virus-encoded Transactivator protein (TAT)
      and regulates viral transcription. Herein, we explore different metallo
      supramolecular triple stranded helicates (cylinders) that target the TAR bulge
      motif and inhibit the formation of TAR-TAT complexes and HIV infection. Cylinders
      that incorporate Ni(II) and Ru(II) showed the most potent anti-viral activity
      with limited evidence of cellular cytotoxicity. These metallo-supramolecular
      compounds provide an exciting avenue for developing a new class of anti-viral
      agents.

PMID- 30190567
TI  - Nebulisation of synthetic lamellar lipids mitigates radiation-induced lung injury
      in a large animal model.
AB  - Methods to protect against radiation-induced lung injury (RILI) will facilitate
      the development of more effective radio-therapeutic protocols for lung cancer and
      may provide the means to protect the wider population in the event of a
      deliberate or accidental nuclear or radiological event. We hypothesised that
      supplementing lipid membranes through nebulization of synthetic lamellar lipids
      would mitigate RILI. Following pre-treatment with either nebulised lamellar
      lipids or saline, anaesthetised sheep were prescribed fractionated radiotherapy
      (30 Gray (Gy) total dose in five 6 Gy fractions at 3-4 days intervals) to a
      defined unilateral lung volume. Gross pathology in radio-exposed lung 37 days
      after the first radiation treatment was consistent between treatment groups and
      consisted of deep red congestion evident on the pleural surface and firmness on
      palpation. Consistent histopathological features in radio-exposed lung were
      subpleural, periarteriolar and peribronchial intra-alveolar oedema, alveolar
      fibrosis, interstitial pneumonia and type II pneumocyte hyperplasia. The
      synthetic lamellar lipids abrogated radiation-induced alveolar fibrosis and
      reduced alpha-smooth muscle actin (ASMA) expression in radio-exposed lung
      compared to saline treated sheep. Administration of synthetic lamellar lipids was
      also associated with an increased number of cells expressing dendritic cell
      lysosomal associated membrane protein throughout the lung.

PMID- 30190569
TI  - Bacterial communities and potential waterborne pathogens within the typical urban
      surface waters.
AB  - Waterborne pathogens have attracted a great deal of attention in the public
      health sector over the last several decades. However, little is known about the
      pathogenic microorganisms in urban water systems. In this study, the bacterial
      community structure of 16 typical surface waters in the city of Beijing were
      analyzed using Illumina MiSeq high-throughput sequencing based on 16S rRNA gene.
      The results showed that Bacteroidetes, Proteobacteria and Actinobacteria were the
      dominant groups in 16 surface water samples, and Betaproteobacteria,
      Alphaproteobacteria, Flavobacteriia, Sphingobacteriia and Actinobacteria were the
      most dominant classes. The dominant genus across all samples was Flavobacterium.
      In addition, fifteen genus level groups of potentialy pathogenic bacteria were
      detected within the 16 water samples, with Pseudomonas and Aeromonas the most
      frequently identified. Spearman correlation analysis demonstrated that richness
      estimators (OTUs and Chao1) were correlated with water temperature, nitrate and
      total nitrogen (p < 0.05), while ammonia-nitrogen and total nitrogen were
      significantly correlated with the percent of total potential pathogens (p <=
      0.05). These results could provide insight into the ecological function and
      health risks of surface water bacterial communities during the process of
      urbanization.

PMID- 30190570
TI  - Novel Imidazole and Methoxybenzylamine Growth Inhibitors Affecting Salmonella
      Cell Envelope Integrity and its Persistence in Chickens.
AB  - The control of Salmonella from farm to fork is challenging due to the emergence
      of antimicrobial-resistant isolates and the limited effects of current control
      methods. Advanced chemical technologies have made accessible a wide range of
      uncharacterized small molecules (SMs) with encouraging chemical properties for
      antimicrobial treatment. Of the 4,182 SMs screened in vitro, four cidal SMs were
      effective at 10 uM and higher against several serotypes, antibiotic-resistant,
      and biofilm embedded Salmonella enterica subsp. enterica serotype Typhimurium by
      altering cell membrane integrity. The four SMs displayed synergistic effects with
      ciprofloxacin, meropenem and cefeprime against Salmonella. Further, the SMs were
      not pernicious to most eukaryotic cells at 200 MUM and cleared internalized
      Salmonella in infected Caco-2, HD11, and THP-1 cells at 6.25 uM and higher. The
      SMs also increased the longevity of Salmonella-infected Galleria mellonella
      larvae and reduced the population of internalized Salmonella Typhimurium. Two of
      the SMs (SM4 and SM5) also reduced S. Typhimurium load in infected chicken ceca
      as well as its systemic translocation into other tissues, with minimal impact on
      the cecal microbiota. This study demonstrated that SMs are a viable source of
      potential antimicrobials applicable in food animal production against Salmonella.

PMID- 30190572
TI  - The aerobic diagenesis of Mesoproterozoic organic matter.
AB  - The Xiamaling Formation in the North China Block contains a well-preserved 1400
      Ma sedimentary sequence with a low degree of thermal maturity. Previous studies
      have confirmed the dynamic and complex nature of this evolving marine setting,
      including the existence of an oxygen-minimum zone, using multi-proxy approaches,
      including iron speciation, trace metal dynamics, and organic geochemistry. Here,
      we investigate the prevailing redox conditions during diagenesis via the
      biomarkers of rearranged hopanes from the finely laminated sediments of the
      organic-rich black shales in Units 2 and 3 of the Xiamaling Formation. We find
      that rearranged hopanes are prominent in the biomarker composition of the oxygen
      minimum zone sediment, which is completely different from that of the sediment in
      the overlying anoxic strata. Since the transition process from hopanes to
      rearranged hopanes requires oxygen via oxidation at the C-l6 alkyl position of
      17alpha(H)-hopanes, we infer that dissolved oxygen led to the transformation of
      hopane precursors into rearranged hopanes during the early stages of diagenesis.
      The use of hopanoid hydrocarbons as biomarkers of marine redox conditions has
      rarely been previously reported, and the hydrocarbon signatures point towards
      oxic bottom waters during the deposition of Unit 3 of the Xiamaling Formation,
      which is consistent with the earlier oxygen-minimum zone environmental
      interpretation of this Unit.

PMID- 30190571
TI  - The Impact of Blood Transfusion on Recurrence and Mortality Following Colorectal
      Cancer Resection: A Propensity Score Analysis of 4,030 Patients.
AB  - Whether blood transfusion exacerbates cancer outcomes after surgery in humans
      remains inconclusive. We utilized a large cohort to investigate the effect of
      perioperative blood transfusion on cancer prognosis following colorectal cancer
      (CRC) resection. Patients with stage I through III CRC undergoing tumour
      resection at a tertiary medical center between 2005 and 2014 were identified and
      evaluated through August 2016. Propensity score matching was used to cancel out
      imbalances in patient characteristics. Postoperative disease-free survival (DFS)
      and overall survival (OS) were analysed using Cox regression model. A total of
      4,030 and 972 patients were analysed before and after propensity score matching.
      Cox regression analyses demonstrated blood transfusion associated with shorter
      DFS and OS before and after matching (hazard ratio: 1.41, 95% CI: 1.2-1.66 for
      DFS; 1.97, 95% CI: 1.6-2.43 for OS). Larger transfusion volume was linked to
      higher overall mortality (<=4 units vs. nil, HR = 1.58; >4 units vs. nil, HR =
      2.32) but not more cancer recurrence. Preoperative anemia was not associated with
      decreased survival after adjusting covariates. Perioperative blood transfusion
      was associated with worse cancer prognosis after curative colorectal resection,
      independently of anemia status. Strategies aimed at minimizing transfusion
      requirements should be further developed.

PMID- 30190573
TI  - Author Correction: Repetitive transcranial magnetic stimulation reveals a causal
      role of the human precuneus in spatial updating.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has not been fixed in the paper.

PMID- 30190574
TI  - DES-Mutation: System for Exploring Links of Mutations and Diseases.
AB  - During cellular division DNA replicates and this process is the basis for passing
      genetic information to the next generation. However, the DNA copy process
      sometimes produces a copy that is not perfect, that is, one with mutations. The
      collection of all such mutations in the DNA copy of an organism makes it unique
      and determines the organism's phenotype. However, mutations are often the cause
      of diseases. Thus, it is useful to have the capability to explore links between
      mutations and disease. We approached this problem by analyzing a vast amount of
      published information linking mutations to disease states. Based on such
      information, we developed the DES-Mutation knowledgebase which allows for
      exploration of not only mutation-disease links, but also links between mutations
      and concepts from 27 topic-specific dictionaries such as human genes/proteins,
      toxins, pathogens, etc. This allows for a more detailed insight into mutation
      disease links and context. On a sample of 600 mutation-disease associations
      predicted and curated, our system achieves precision of 72.83%. To demonstrate
      the utility of DES-Mutation, we provide case studies related to known or
      potentially novel information involving disease mutations. To our knowledge, this
      is the first mutation-disease knowledgebase dedicated to the exploration of this
      topic through text-mining and data-mining of different mutation types and their
      associations with terms from multiple thematic dictionaries.

PMID- 30190575
TI  - Risk factors for Streptococcus suis infection: A systematic review and meta
      analysis.
AB  - Streptococcus suis (S. suis) is a gram-positive bacterial pathogen in pigs which
      can cause serious infections in human including meningitis, and septicaemia
      resulting in serious complications. There were discrepancies between different
      data and little is known concerning associated risk factors of S. suis. A
      systematic review and meta-analysis was conducted to investigate on S. suis
      infection risk factors in human. We searched eight relevant databases using the
      MeSH terms "Streptococcus suis" OR "Streptococcus suis AND infection" limited in
      human with no time nor language restriction. Out of 4,999 articles identified, 32
      and 3 studies were included for systematic review and meta-analysis respectively
      with a total of 1,454 Streptococcus suis cases reported. S. suis patients were
      generally adult males and the elderly. The mean age ranged between 37 to 63
      years. Meningitis was the most common clinical manifestation, and deafness was
      the most common sequelae found among survivors followed by vestibular
      dysfunction. Infective endocarditis was also noted as among the most common
      clinical presentations associated with high mortality rate in a few studies. Meta
      analyses categorized by type of control groups (community control, and non-S.
      suis sepsis) were done among 850 participants in 3 studies. The combined odd
      ratios for studies using community control groups and non-S. Suis sepsis as
      controls respectively were 4.63 (95% CI 2.94-7.29) and 78.00 (95% CI 10.38
      585.87) for raw pork consumption, 4.01 (95% CI 2.61-6.15) and 3.03 (95% CI 1.61
      5.68) for exposure to pigs or pork, 11.47, (95% CI 5.68-23.14) and 3.07 (95% CI
      1.81-5.18) for pig-related occupation and 3.56 (95% CI 2.18-5.80) and 5.84 (95%
      CI 2.76-12.36) for male sex. The results were found to be significantly
      associated with S. suis infection and there was non-significant heterogeneity.
      History of skin injury and underlying diseases were noted only a small percentage
      in most studies. Setting up an effective screening protocol and public health
      interventions would be effective to enhance understanding about the disease.

PMID- 30190576
TI  - Author Correction: AMP kinase promotes glioblastoma bioenergetics and tumour
      growth.
AB  - In the version of this Article originally published, in ref. 34 the first
      author's name was spelled incorrectly. The correct reference is: Rodon, L. et al.
      Active CREB1 promotes a malignant TGFbeta2 autocrine loop in glioblastoma. Cancer
      Discov. 10, 1230-1241 (2014). This has now been amended in all online versions of
      the Article.

PMID- 30190577
TI  - Periodontal status and lung function decline in the community: the Hisayama
      study.
AB  - This study aimed to determine whether periodontal status is related to a decline
      in lung function in a general Japanese population. We followed a total of 1,650
      community-dwelling individuals (>=40 years) without chronic obstructive pulmonary
      disease, with at least one teeth, for 3 years. Periodontal status was assessed at
      baseline by clinical attachment loss (CAL) and probing pocket depth (PPD) at two
      sites for each tooth, and the mean values were calculated for each subject. Lung
      function was measured at baseline and follow-up using spirometry, and
      longitudinal decline in forced expiratory volume in one second (FEV1) was
      calculated. Multivariate Poisson regression with robust error variance was used
      to estimate risk ratio (RR). After adjusting for potential confounders including
      smoking status, there was a tendency for the adjusted RR of developing rapid lung
      function decline (>=160 mL/3years, the highest quartile of the distribution of
      FEV1 declines) to increase as mean CAL levels increased (P trend = 0.039).
      Likewise, a positive association was observed between mean PPD levels and RR of
      developing rapid lung function decline (P trend = 0.047). Our findings suggest
      deterioration of periodontal status could be a risk factor for rapid lung
      function decline in the general Japanese population.

PMID- 30190578
TI  - High Trapped Fields in C-doped MgB2 Bulk Superconductors Fabricated by
      Infiltration and Growth Process.
AB  - The grain boundaries in superconducting MgB2 are known to form effective magnetic
      flux pinning sites and, consequently, bulk MgB2 containing a fine-grain
      microstructure fabricated from nanoscale Mg and B precursor powders exhibits good
      magnetic field-trapping performance below 20 K. We report here that the trapped
      field of MgB2 bulk superconductors fabricated by an infiltration and growth
      process to yield a dense, pore-free microstructure, can be enhanced significantly
      by carbon-doping, which increases intra-band scattering within the
      superconducting grains. A maximum trapped field of 4.15 T has been measured at
      7.5 K at the centre of a five-sample stack of Mg(B1-xiCxi)2 bulk superconductors
      processed by infiltration and growth, which not only represents a ~40% increase
      in trapped field observed compared to undoped bulk MgB2, but also is the highest
      trapped field reported to date in MgB2 samples processed under ambient pressure.
      The trapped field is observed to decay at a rate of <2%/day at 10 K, which
      suggests that bulk MgB2 superconductors fabricated using the infiltration and
      growth technique can be used potentially to generate stable, high magnetic fields
      for a variety of engineering applications.

PMID- 30190579
TI  - GM1 ganglioside prevents axonal regeneration inhibition and cognitive deficits in
      a mouse model of traumatic brain injury.
AB  - Traumatic Brain Injury (TBI) is one of the most common causes of neurological
      damage in young populations. It has been previously suggested that one of the
      mechanisms that underlie brain injury is Axonal Outgrowth Inhibition (AOI) that
      is caused by altered composition of the gangliosides on the axon surface. In the
      present study, we have found a significant reduction of GM1 ganglioside levels in
      the cortex in a closed head traumatic brain injury model of a mouse, induced by a
      weight drop device. In addition, axonal regeneration in the brains of the injured
      mice was affected as seen by the expression of the axonal marker pNF-H and the
      growth cones (visualized by F-actin and beta-III-tubulin). NeuN immunostaining
      revealed mTBI-induced damage to neuronal survival. Finally, as expected, spatial
      and visual memories (measured by the Y-maze and the Novel Object Recognition
      tests, respectively) were also damaged 7 and 30 days post injury. A single low
      dose of GM1 shortly after the injury (2 mg/kg; IP) prevented all of the deficits
      mentioned above. These results reveal additional insights into the
      neuroprotective characteristics of GM1 in prevention of biochemical, cellular and
      cognitive changes caused by trauma, and may suggest a potential intervention for
      mTBI.

PMID- 30190580
TI  - A scoring system to detect fixed airflow limitation in smokers from simple easy
      to-use parameters.
AB  - No validated screening method currently exists for Chronic Obstructive Pulmonary
      Disease (COPD) in smokers. Therefore, we constructed a predictive model with
      simple parameters that can be applied for COPD screening to detect fixed airflow
      limitation. This observational cross-sectional study included a random sample of
      222 smokers with no previous diagnosis of COPD undertaken in a Spanish region in
      2014-2016. The main variable was fixed airflow limitation by spirometry. The
      secondary variables (COPD factors) were: age, gender, smoking (pack-years and
      Fagerstrom test), body mass index, educational level, respiratory symptoms and
      exacerbations. A points system was developed to predict fixed airflow limitation
      based on secondary variables. The model was validated internally through
      bootstrapping, determining discrimination and calibration. The system was then
      integrated into a mobile application for Android. Fifty-seven patients (25.7%)
      presented fixed airflow limitation. The points system included as predictors:
      age, pack-years, Fagerstrom test and presence of respiratory symptoms. Internal
      validation of the system was very satisfactory, both in discrimination and
      calibration. In conclusion, a points system has been constructed to predict fixed
      airflow limitation in smokers with no previous COPD. This system can be
      integrated as a screening tool, though it should be externally validated in other
      geographical regions.

PMID- 30190582
TI  - Route towards extreme optical pulsation in linear cavity ultrafast fibre lasers.
AB  - Pathways towards the generation of extreme optical pulsation in a chaotic
      transition regime in a linear fibre laser cavity configuration are presented. In
      a thulium mode-locked fibre laser, extreme events that can be controllably
      induced by manipulating the cavity birefringence for pulse energies exceeding the
      single soliton pulse operating regime are studied in detail for the first time.
      While a solitonic pulsation structure at the fundamental repetition rate is
      maintained, additional energy is shed in a chaotic manner, leading to broader
      spectral generation and shorter pulse durations whose behaviour deviates
      significantly from a classical statistical distribution. These pulses display
      markedly different characteristics from any previously reported extreme events in
      fibre lasers associated with multiple solitons and pulse bunching, thus
      presenting a novel observation of extreme pulsation. Detailed noise studies
      indicate that significant enhancement of relaxation oscillations, modulation
      instability and the interplay with reabsorption mechanisms contribute in this
      transient chaotic regime. The extreme pulsation generated in a compact fibre
      laser without any additional nonlinear attractors can provide an attractive
      platform to accelerate the exploration of the underlying physics of the chaos
      observed in mode-locked laser systems and can lead to novel fibre laser cavity
      designs.

PMID- 30190581
TI  - Human susceptibility to social influence and its neural correlates are related to
      perceived vulnerability to extrinsic morbidity risks.
AB  - Humans considerably vary in the degree to which they rely on their peers to make
      decisions. Why? Theoretical models predict that environmental risks shift the
      cost-benefit trade-off associated with the exploitation of others' behaviours
      (public information), yet this idea has received little empirical support. Using
      computational analyses of behaviour and multivariate decoding of
      electroencephalographic activity, we test the hypothesis that perceived
      vulnerability to extrinsic morbidity risks impacts susceptibility to social
      influence, and investigate whether and how this covariation is reflected in the
      brain. Data collected from 261 participants tested online revealed that perceived
      vulnerability to extrinsic morbidity risks is positively associated with
      susceptibility to follow peers' opinion in the context of a standard face
      evaluation task. We found similar results on 17 participants tested in the
      laboratory, and showed that the sensitivity of EEG signals to public information
      correlates with the participants' degree of vulnerability. We further
      demonstrated that the combination of perceived vulnerability to extrinsic
      morbidity with decoding sensitivities better predicted social influence scores
      than each variable taken in isolation. These findings suggest that susceptibility
      to social influence is partly calibrated by perceived environmental risks,
      possibly via a tuning of neural mechanisms involved in the processing of public
      information.

PMID- 30190584
TI  - A novel paradigm to study spatial memory skills in blind individuals through the
      auditory modality.
AB  - Spatial memory is a multimodal representation of the environment, which can be
      mediated by different sensory signals. Here we investigate how the auditory
      modality influences memorization, contributing to the mental representation of a
      scene. We designed an audio test inspired by a validated spatial memory test, the
      Corsi-Block test for blind individuals. The test was carried out in two different
      conditions, with non-semantic and semantic stimuli, presented in different
      sessions and displaced on an audio-tactile device. Furthermore, the semantic
      sounds were spatially displaced in order to reproduce an audio scene, explored by
      participants during the test. Thus, we verified if semantic rather than non
      semantic sounds are better recalled and whether exposure to an auditory scene can
      enhance memorization skills. Our results show that sighted subjects performed
      better than blind participants after the exploration of the semantic scene. This
      suggests that blind participants focus on the perceived sound positions and do
      not use items' locations learned during the exploration. We discuss these results
      in terms of the role of visual experience on spatial memorization skills and the
      ability to take advantage of semantic information stored in the memory.

PMID- 30190586
TI  - Surface Plasmon Coupling in GaN:Eu Light Emitters with Metal-Nitrides.
AB  - Metal-nitrides of hafnium nitride (HfN), zirconium nitride (ZrN) and titanium
      nitride (TiN) are investigated as plasmonic materials to enhance the internal
      quantum efficiency of a GaN:Eu red light emitter. Theoretical calculations are
      performed to evaluate the surface plasmon polariton dispersion relation and
      Purcell enhancement factor for a single metal-nitride layer on top of the GaN:Eu
      emitter. Our findings suggest that among the metal-nitrides investigated in this
      study, TiN is the most promising candidate for use as plasmonic material to
      increase the internal quantum efficiency in GaN:Eu red light emitters.

PMID- 30190583
TI  - Polarity of CD4+ T cells towards the antigen presenting cell is regulated by the
      Lck adapter TSAd.
AB  - Polarization of T cells towards the antigen presenting cell (APC) is critically
      important for appropriate activation and differentiation of the naive T cell.
      Here we used imaging flow cytometry (IFC) and show that the activation induced
      Lck and Itk adapter T cell specific adapter protein (TSAd), encoded by SH2D2A,
      modulates polarization of T cells towards the APC. Upon exposure to APC
      presenting the cognate antigen Id, Sh2d2a-/- CD4+ T cells expressing Id-specific
      transgenic T cell receptor (TCR), displayed impaired polarization of F-actin and
      TCR to the immunological synapse (IS). Sh2d2a-/- T-cells that did polarize F
      actin and TCR still displayed impaired polarization of PKCxi, PAR3 and the
      microtubule-organizing center (MTOC). In vitro differentiation of activated
      Sh2d2a-/- T cells was skewed towards an effector memory (Tem) rather than a
      central memory (Tcm) phenotype. A similar trend was observed for Id-specific TCR
      Sh2d2a-/- T cells stimulated with APC and cognate antigen. Taken together our
      data suggest that TSAd modulates differentiation of experienced T cells possibly
      through polarization of CD4+ T cells towards the APC.

PMID- 30190585
TI  - Association of Kidney Function with Infections by Multidrug-Resistant Organisms:
      An Electronic Medical Record Analysis.
AB  - : Antibiotic resistance is a major global health threat. High prevalences of
      colonization and infection with multi-drug resistance organisms (MDROs) have been
      reported in patients undergoing dialysis. It is unknown if this finding extends
      to patients with mild and moderate/severe kidney disease. An observational study
      included all adult incident patients hospitalized with a discharge diagnosis of
      infection in four hospitals from Guangzhou, China. INCLUSION CRITERIA: Serum
      creatinine measurement at admission together with microbial culture confirmed
      infections. Exclusion criterion: Undergoing renal replacement therapy. Four
      categories of Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
      estimated glomerular filtration rate (eGFR) were compared: eGFR >= 105, 60-104
      (reference), 30-59, and <30 ml/min/1.73 m2. The odds ratio of MDROs, defined as
      specific pathogens (Staphylococcus aureus, Enterococcus spp., Enterobacteriaceae,
      Pseudomonas aeruginosa and Acinetobacter spp.) resistant to three or more
      antibiotic classes, were calculated using a multivariable logistic regression
      model across eGFR strata. Of 94,445 total microbial culture records, 7,288 first
      positive cultures matched to infection diagnosis were selected. Among them, 5,028
      (68.9%) were potential MDROs. The odds of infections by MDROs was 19% and 41%
      higher in those with eGFR between 30-59 ml/min/1.73 m2 (Adjusted odds ratio,
      AOR): 1.19, 95% CI:1.02-1.38, P = 0.022) and eGFR < 30 ml/min/1.73 m2 (AOR: 1.41,
      95% CI:1.12-1.78, P = 0.004), respectively. Patients with impaired renal function
      have a higher risk of infections by MDROs. Kidney dysfunction at admission may be
      an indicator for need of closer attention to microbial culture results requiring
      subsequent change of antibiotics.

PMID- 30190587
TI  - Strain-specific differences in brain gene expression in a hydrocephalic mouse
      model with motile cilia dysfunction.
AB  - Congenital hydrocephalus results from cerebrospinal fluid accumulation in the
      ventricles of the brain and causes severe neurological damage, but the underlying
      causes are not well understood. It is associated with several syndromes,
      including primary ciliary dyskinesia (PCD), which is caused by dysfunction of
      motile cilia. We previously demonstrated that mouse models of PCD lacking ciliary
      proteins CFAP221, CFAP54 and SPEF2 all have hydrocephalus with a strain-dependent
      severity. While morphological defects are more severe on the C57BL/6J (B6)
      background than 129S6/SvEvTac (129), cerebrospinal fluid flow is perturbed on
      both backgrounds, suggesting that abnormal cilia-driven flow is not the only
      factor underlying the hydrocephalus phenotype. Here, we performed a microarray
      analysis on brains from wild type and nm1054 mice lacking CFAP221 on the B6 and
      129 backgrounds. Expression differences were observed for a number of genes that
      cluster into distinct groups based on expression pattern and biological function,
      many of them implicated in cellular and biochemical processes essential for
      proper brain development. These include genes known to be functionally relevant
      to congenital hydrocephalus, as well as formation and function of both motile and
      sensory cilia. Identification of these genes provides important clues to
      mechanisms underlying congenital hydrocephalus severity.

PMID- 30190588
TI  - Polymeric nanocapsules embedded with ultra-small silver nanoclusters for
      synergistic pharmacology and improved oral delivery of Docetaxel.
AB  - Despite of the remarkable cytotoxic and imaging potential of ultra-small metal
      nanoclusters, their toxicity-free and targeted delivery to cancerous cells
      remains a substantial challenge that hinders their clinical applications. In this
      study, a polymeric scaffold was first synthesized by grafting folic acid and
      thiol groups to chitosan (CS) for cancer cell targeting and improved gastric
      permeation. Furthermore, silver nanocluster (Ag NCs) were synthesized in situ,
      within CS scaffold by microwave irradiation and core-shell nanocapsules (NCPs)
      were prepared with hydrophobic docetaxel (DTX) in the core and Ag NCs embedded CS
      in the shell. A significant cytotoxicity synergism (~300 folds) was observed for
      DTX with co-delivery of Ag NCs against breast cancer MDA-MB-231 cells. Following
      oral administration, the DTX-Ag-NCPs increased bioavailability due to enhanced
      drug transport across gut (9 times), circulation half-life (~6.8 times) and mean
      residence time (~6.7 times), as compared to the control DTX suspension. Moreover,
      14 days acute oral toxicity of the DTX-Ag-NCPs was performed in mice and
      evaluated for changes in blood biochemistry parameters, organ to body weight
      index and histopathology of liver and kidney tissues that revealed no significant
      evidence of toxicity suggesting the safety and efficiency of the DTX-Ag-NCPs as
      hybrid nanocarrier for biocompatible delivery of metal nanoclusters.

PMID- 30190589
TI  - Regenerating a monoblock to obturate root canalsvia a mineralising strategy.
AB  - To develop a novel strategy for sealing and obturating dental root canals by
      tooth-like tissue regeneration, premolars with mature root apices were freshly
      collected, and root canals were prepared by following the clinical protocols in
      vitro. The teeth were immersed in supersaturated calcium and phosphate solution
      containing gallic acid and fluoride. At certain intervals, the dental roots were
      taken out, and their mineral precipitates were characterised by scanning electron
      microscopy, energy-dispersive spectroscopy mapping, X-ray diffraction and
      transmission electron microscopy. The cytocompatibility of the mineralizing
      products were evaluated with rabbit bone-marrow-derived mesenchymal stem cells in
      vitro. Results showed that the precipitates were mainly composed of fluoridated
      hydroxyapatite with ahexagonal prism morphology. Fluoridated hydroxyapatite
      initially nucleated and grew from the root canal dentine surface to the root
      canal centre. The fluoridated hydroxyapatite precipitate and root canal dentine
      intergraded together such that the interface became hardly distinguishable. The
      fluoridated hydroxyapatite precipitate grew into and obturated the dentinal
      tubules. In the root canal, the regenerated fluoridated hydroxyapatite densely
      packed and bundled together with a c-axis extension. After 7 days of
      mineralisation, the root canal was completely obturated, and the apical foramen
      was sealed. The mineralizing products had good biocompatibility with the cells,
      and the cells grew well on the mineralized surface. Biomimetic mineralisation
      strategy provides a novel means to regenerate tooth-like tissue to seal the root
      canal system permanently other than by passive synthetic material filling.

PMID- 30190590
TI  - SALL4 mediates teratogenicity as a thalidomide-dependent cereblon substrate.
AB  - Targeted protein degradation via small-molecule modulation of cereblon offers
      vast potential for the development of new therapeutics. Cereblon-binding
      therapeutics carry the safety risks of thalidomide, which caused an epidemic of
      severe birth defects characterized by forelimb shortening or phocomelia. Here we
      show that thalidomide is not teratogenic in transgenic mice expressing human
      cereblon, indicating that binding to cereblon is not sufficient to cause birth
      defects. Instead, we identify SALL4 as a thalidomide-dependent cereblon
      neosubstrate. Human mutations in SALL4 cause Duane-radial ray, IVIC, and acro
      renal-ocular syndromes with overlapping clinical presentations to thalidomide
      embryopathy, including phocomelia. SALL4 is degraded in rabbits but not in
      resistant organisms such as mice because of SALL4 sequence variations. This work
      expands the scope of cereblon neosubstrate activity within the formerly
      'undruggable' C2H2 zinc finger family and offers a path toward safer therapeutics
      through an improved understanding of the molecular basis of thalidomide-induced
      teratogenicity.

PMID- 30190591
TI  - Small noncoding RNA profiles along alternative developmental trajectories in an
      annual killifish.
AB  - Embryonic development of Austrofundulus limnaeus can occur along two phenotypic
      trajectories that are physiologically and biochemically distinct. Phenotype
      appears to be influenced by maternal provisioning based on the observation that
      young females produce predominately non-diapausing embryos and older females
      produce mostly diapausing embryos. Embryonic incubation temperature can override
      this pattern and alter trajectory. We hypothesized that temperature-induced
      phenotypic plasticity may be regulated by post-transcriptional modification via
      noncoding RNAs. As a first step to exploring this possibility, RNA-seq was used
      to generate transcriptomic profiles of small noncoding RNAs in embryos developing
      along the two alternative trajectories. We find distinct profiles of mature
      sequences belonging to the miR-10 family expressed in increasing abundance during
      development and mature sequences of miR-430 that follow the opposite pattern.
      Furthermore, miR-430 sequences are enriched in escape trajectory embryos. MiR-430
      family members are known to target maternally provisioned mRNAs in zebrafish and
      may operate similarly in A. limnaeus in the context of normal development, and
      also by targeting trajectory-specific mRNAs. This expression pattern and function
      for miR-430 presents a potentially novel model for maternal-embryonic conflict in
      gene regulation that provides the embryo the ability to override maternal
      programming in the face of altered environmental conditions.

PMID- 30190592
TI  - Predicting IDH genotype in gliomas using FET PET radiomics.
AB  - Mutations in the isocitrate dehydrogenase (IDH mut) gene have gained paramount
      importance for the prognosis of glioma patients. To date, reliable techniques for
      a preoperative evaluation of IDH genotype remain scarce. Therefore, we
      investigated the potential of O-(2-[18F]fluoroethyl)-L-tyrosine (FET) PET
      radiomics using textural features combined with static and dynamic parameters of
      FET uptake for noninvasive prediction of IDH genotype. Prior to surgery, 84
      patients with newly diagnosed and untreated gliomas underwent FET PET using a
      standard scanner (15 of 56 patients with IDH mut) or a dedicated high-resolution
      hybrid PET/MR scanner (11 of 28 patients with IDH mut). Static, dynamic and
      textural parameters of FET uptake in the tumor area were evaluated. Diagnostic
      accuracy of the parameters was evaluated using the neuropathological result as
      reference. Additionally, FET PET and textural parameters were combined to further
      increase the diagnostic accuracy. The resulting models were validated using cross
      validation. Independent of scanner type, the combination of standard PET
      parameters with textural features increased significantly diagnostic accuracy.
      The highest diagnostic accuracy of 93% for prediction of IDH genotype was
      achieved with the hybrid PET/MR scanner. Our findings suggest that the
      combination of conventional FET PET parameters with textural features provides
      important diagnostic information for the non-invasive prediction of the IDH
      genotype.

PMID- 30190593
TI  - Convergence of sensory and limbic noxious input into the anterior insula and the
      emergence of pain from nociception.
AB  - Two parallel di-synaptic routes convey nociceptive input to the telencephalon:
      the spino-thalamic system projecting principally to the posterior insula, and the
      spino-parabrachial pathway reaching the amygdalar nucleus. Interplay between the
      two systems underlies the sensory and emotional aspects of pain, and was explored
      here in humans with simultaneous recordings from the amygdala, posterior and
      anterior insulae. Onsets of thermo-nociceptive responses were virtually identical
      in the posterior insula and the amygdalar complex, but no significant functional
      connectivity was detected between them using coherence analysis. Anterior insular
      sectors responded with ~30 ms delay relative to both the posterior insula and the
      amygdala. While intra-insular functional correlation was significant during the
      whole analysis period, coherence between the anterior insula and the amygdala
      became significant after 700 ms of processing. Phase lags indicated information
      transfer initially directed from the amygdalar complex to the insula. Parallel
      but independent activation of sensory and limbic nociceptive networks appear to
      converge in the anterior insula in less than one second. While the anterior
      insula is often considered as providing input into the limbic system, our results
      underscore its reverse role, i.e., receiving and integrating very rapidly limbic
      with sensory input, to initiate a perceptual decision on the stimulus
      'painfulness'.

PMID- 30190594
TI  - Viral communities associated with porcine respiratory disease complex in
      intensive commercial farms in Sichuan province, China.
AB  - Porcine respiratory disease complex (PRDC), a common piglet disease, causes
      substantive economic losses in pig farming. To investigate the viral diversity
      associated with PRDC, the viral communities in serum and nasal swabs from 26 PRDC
      affected piglets were investigated using metagenomics. By deep sequencing and de
      novo assembly, 17 viruses were identified in two pooled libraries (16 viruses
      from serum, nine from nasal swabs). Porcine circovirus (PCV)-2, porcine
      reproductive and respiratory syndrome virus (PRRSV) and pseudorabies virus, all
      commonly associated with PRDC, were identified in the two pooled samples by
      metagenomics, but most viruses comprised small linear and circular DNAs (e.g.
      parvoviruses, bocaviruses and circoviruses). PCR was used to compare the
      detection rates of each virus in the serum samples from 36 PRDC-affected piglets
      versus 38 location-matched clinically healthy controls. The average virus
      category per sample was 6.81 for the PRDC-affected piglets and 4.09 for the
      controls. Single or co-infections with PCV-2 or PRRSV had very high detection
      rates in the PRDC-affected piglets. Interestingly, porcine parvovirus (PPV)-2,
      PPV-3, PPV-6 and torque teno sus virus 1a were significantly associated with
      PRDC. These results illustrate the complexity of viral communities in the PRDC
      affected piglets and highlight the candidate viruses associated with it.

PMID- 30190596
TI  - Architecture of Pol II(G) and molecular mechanism of transcription regulation by
      Gdown1.
AB  - Tight binding of Gdown1 represses RNA polymerase II (Pol II) function in a manner
      that is reversed by Mediator, but the structural basis of these processes is
      unclear. Although Gdown1 is intrinsically disordered, its Pol II interacting
      domains were localized and shown to occlude transcription factor IIF (TFIIF) and
      transcription factor IIB (TFIIB) binding by perfect positioning on their Pol II
      interaction sites. Robust binding of Gdown1 to Pol II is established by
      cooperative interactions of a strong Pol II binding region and two weaker binding
      modulatory regions, thus providing a mechanism both for tight Pol II binding and
      transcription inhibition and for its reversal. In support of a physiological
      function for Gdown1 in transcription repression, Gdown1 co-localizes with Pol II
      in transcriptionally silent nuclei of early Drosophila embryos but re-localizes
      to the cytoplasm during zygotic genome activation. Our study reveals a self
      inactivation through Gdown1 binding as a unique mode of repression in Pol II
      function.

PMID- 30190595
TI  - The 2015 landslide and tsunami in Taan Fiord, Alaska.
AB  - Glacial retreat in recent decades has exposed unstable slopes and allowed deep
      water to extend beneath some of those slopes. Slope failure at the terminus of
      Tyndall Glacier on 17 October 2015 sent 180 million tons of rock into Taan Fiord,
      Alaska. The resulting tsunami reached elevations as high as 193 m, one of the
      highest tsunami runups ever documented worldwide. Precursory deformation began
      decades before failure, and the event left a distinct sedimentary record, showing
      that geologic evidence can help understand past occurrences of similar events,
      and might provide forewarning. The event was detected within hours through
      automated seismological techniques, which also estimated the mass and direction
      of the slide - all of which were later confirmed by remote sensing. Our field
      observations provide a benchmark for modeling landslide and tsunami hazards.
      Inverse and forward modeling can provide the framework of a detailed
      understanding of the geologic and hazards implications of similar events. Our
      results call attention to an indirect effect of climate change that is increasing
      the frequency and magnitude of natural hazards near glaciated mountains.

PMID- 30190598
TI  - Structural basis of mitochondrial transcription.
AB  - The mitochondrial genome is transcribed by a single-subunit DNA-dependent RNA
      polymerase (mtRNAP) and its auxiliary factors. Structural studies have elucidated
      how mtRNAP cooperates with its dedicated transcription factors to direct RNA
      synthesis: initiation factors TFAM and TFB2M assist in promoter-DNA binding and
      opening by mtRNAP while the elongation factor TEFM increases polymerase
      processivity to the levels required for synthesis of long polycistronic mtRNA
      transcripts. Here, we review the emerging body of structural and functional
      studies of human mitochondrial transcription, provide a molecular movie that can
      be used for teaching purposes and discuss the open questions to guide future
      directions of investigation.

PMID- 30190597
TI  - Structure of the mechanosensitive OSCA channels.
AB  - Mechanosensitive ion channels convert mechanical stimuli into a flow of ions.
      These channels are widely distributed from bacteria to higher plants and humans,
      and are involved in many crucial physiological processes. Here we show that two
      members of the OSCA protein family in Arabidopsis thaliana, namely AtOSCA1.1 and
      AtOSCA3.1, belong to a new class of mechanosensitive ion channels. We solve the
      structure of the AtOSCA1.1 channel at 3.5-A resolution and AtOSCA3.1 at 4.8-A
      resolution by cryo-electron microscopy. OSCA channels are symmetric dimers that
      are mediated by cytosolic inter-subunit interactions. Strikingly, they have
      structural similarity to the mammalian TMEM16 family proteins. Our structural
      analysis accompanied with electrophysiological studies identifies the ion
      permeation pathway within each subunit and suggests a conformational change model
      for activation.

PMID- 30190601
TI  - Armchair MoS2 nanoribbons turned into half metals through deposition of
      transition-metal and Si atomic chains.
AB  - MoS2 nanoribbons with armchair-terminated edges are semiconductors suitable for
      the tuning of electronic and magnetic properties. Our first-principles density
      function calculations reveal that a variety of transition-metal atomic chains
      deposited on some of the ribbons is able to transform the semiconductors into
      half metals, allowing transport of 100% spin-polarized currents. Furthermore, we
      found that a Si atomic chain is equally capable of achieving half metallicity
      when adsorbed on the same nanoribbon. These results should be useful for
      spintronic application.

PMID- 30190599
TI  - Lateral Ventricle Enlargement and Cortical Thinning in Idiopathic Normal-pressure
      Hydrocephalus Patients.
AB  - We utilized three-dimensional, surface-based, morphometric analysis to
      investigate ventricle shape between 2 groups: (1) idiopathic normal-pressure
      hydrocephalus (INPH) patients who had a positive response to the cerebrospinal
      fluid tap test (CSFTT) and (2) healthy controls. The aims were (1) to evaluate
      the location of INPH-related structural abnormalities of the lateral ventricles
      and (2) to investigate relationships between lateral ventricular enlargement and
      cortical thinning in INPH patients. Thirty-three INPH patients and 23 healthy
      controls were included in this study. We used sparse canonical correlation
      analysis to show correlated regions of ventricular surface expansion and cortical
      thinning. Significant surface expansion in the INPH group was observed mainly in
      clusters bilaterally located in the superior portion of the lateral ventricles,
      adjacent to the high convexity of the frontal and parietal regions. INPH patients
      showed a significant bilateral expansion of both the temporal horns of the
      lateral ventricles and the medial aspects of the frontal horns of the lateral
      ventricles to surrounding brain regions, including the medial frontal lobe.
      Ventricular surface expansion was associated with cortical thinning in the
      bilateral orbitofrontal cortex, bilateral rostral anterior cingulate cortex, left
      parahippocampal cortex, left temporal pole, right insula, right inferior temporal
      cortex, and right fusiform gyrus. These results suggest that patients with INPH
      have unique patterns of ventricular surface expansion. Our findings encourage
      future studies to elucidate the underlying mechanism of lateral ventricular
      morphometric abnormalities in INPH patients.

PMID- 30190600
TI  - Analytical ultracentrifugation in saliva research: Impact of green tea
      astringency and its significance on the in-vivo aroma release.
AB  - Current saliva testing methods rely on cutting edge yet expensive techniques for
      the detection and analysis of genetic material, proteins and biomarkers for
      clinical use. However, these techniques are limited in scope and often cannot be
      used with complex food materials. We propose an efficient ex-vivo tool for
      evaluating biologically relevant interactions between food components and human
      saliva using sedimentation velocity analytical ultracentrifugation (SV-AUC). We
      evaluated macromolecular content from "unstimulated" (US) and "stimulated" (SS)
      samples pooled from 5 healthy volunteers. Over 90% of total saliva protein
      consisted of alpha-amylase and mucin, and up to 10% was secretory immunoglobulin
      A (SIgA). It was shown that alpha-amylase concentration increased upon parafilm
      stimulation, which lead to a decrease in the viscosity of saliva. Then, we used a
      simple food system (green tea) to evaluate changes in the salivary protein
      content caused by green tea polyphenols. It was found that aroma release from
      green tea is highly influenced by interactions between alpha-amylase and
      polyphenol epigallocatechin 3-gallate (EGCG). This interaction was found to
      increase the viscosity of the salivary bulk, suggested to contribute to
      astringency, and increased the concentrations of beta-ionone, benzaldehyde and
      isovaleraldehyde (P < 0.01), suggested to play a significant role in the
      characteristic flavour of green tea.

PMID- 30190602
TI  - Ag/MnO2 Composite Sheath-Core Structured Yarn Supercapacitors.
AB  - One-dimensional (1D) yarn or fiber-based supercapacitors that have small
      diameter, volume and high mechanical strength are needed due to the demands on
      power source for wearable electronics, micro-devices, and implantable medical
      devices. The composite sheath is fabricated on a commercially available CNT yarn
      substrate by alternating depositions of MnO2 and Ag layers. Synergistic effect of
      high loading level of pseudocapacitive MnO2 and reasonably improved rate
      capability are achieved. In the composite sheath, the interconnected networks
      provide electrical contact between MnO2 aggregates and adjacent Ag layer. The
      conductive Ag inter layers shorten the solid-state charge diffusion length in the
      MnO2. Moreover, generated electrons during the charge/discharge process can be
      collected rapidly by the adjacent Ag layer, therefore, the great extents of MnO2
      could be loaded onto the surface of CNT core fiber electrode without a
      significant rate-capability degradation. Due to the high MnO2 loading level, the
      composite sheath-core yarn supercapacitor showed excellent specific areal
      capacitance (322.2 mF/cm2) and according energy density (18.3 uWh/cm2).

PMID- 30190603
TI  - The recombinase Rad51 plays a key role in events of genetic exchange in
      Trypanosoma cruzi.
AB  - Detection of genetic exchange has been a limiting factor to deepen the knowledge
      on the mechanisms by which Trypanosoma cruzi is able to generate progeny and
      genetic diversity. Here we show that incorporation of halogenated thymidine
      analogues, followed by immunostaining, is a reliable method not only to detect T.
      cruzi fused-cell hybrids, but also to quantify their percentage in populations of
      this parasite. Through this approach, we were able to detect and quantify fused
      cell hybrids of T. cruzi clones CL Brener and Y. Given the increased detection of
      fused-cell hybrids in naturally-occurring hybrid CL Brener strain, which displays
      increased levels of RAD51 and BRCA2 transcripts, we further investigated the role
      of Rad51 - a recombinase involved in homologous recombination - in the process of
      genetic exchange. We also verified that the detection of fused-cell hybrids in T.
      cruzi overexpressing RAD51 is increased when compared to wild-type cells,
      suggesting a key role for Rad51 either in the formation or in the stabilization
      of fused-cell hybrids in this organism.

PMID- 30190604
TI  - Imidazole Compounds for Protecting Choroidal Endothelial Cells from Complement
      Injury.
AB  - Age-related macular degeneration (AMD) is a common, blinding disease associated
      with increased complement system activity. Eyes with AMD show elevated
      accumulation of the membrane attack complex (MAC) in the choriocapillaris and
      degeneration of macular choriocapillaris endothelial cells (ECs). Thus, one could
      reasonably conclude that the endothelial cell death that occurs in AMD is due to
      injury by the MAC. We therefore sought to identify strategies for protecting ECs
      against MAC lysis. RF/6A endothelial cells were pre-incubated with a library of
      FDA-approved small molecules, followed by incubation with complement intact human
      serum quantification of cell death. Two closely related molecules identified in
      the screen, econazole nitrate and miconazole nitrate, were followed in validation
      and mechanistic studies. Both compounds reduced lysis of choroidal ECs treated
      with complement-intact serum, across a range of doses from 1 to 100 uM. Cell
      rescue was confirmed in mouse primary choroidal ECs. Both exosome release and
      cell surface roughness (assessed using a Holomonitor system) were reduced by drug
      pretreatment in RF/6A cells, whereas endosome formation increased with both
      drugs, consistent with imidazole-mediated alterations of cell surface dynamics.
      The results in the current study provide further proof of principle that small
      molecules can protect choroidal ECs from MAC-induced cell death and suggest that
      FDA approved compounds may be beneficial in reducing vascular loss and
      progression of AMD.

PMID- 30190606
TI  - Mn-induced Ferromagnetic Semiconducting Behavior with Linear Negative
      Magnetoresistance in Sr4(Ru1-xMnx)3O10 Single Crystals.
AB  - Triple-layered Sr4Ru3O10 is a unique ferromagnet with the central RuO6 layer
      behaving differently from two outer layers both crystallographically and
      magnetically. We report that the partial substitution of Ru by smaller Mn gives
      rise to modification in crystal structure, electronic and magnetic properties of
      Sr4(Ru1-xMnx)3O10. Through the single crystal X-ray diffraction refinement, we
      find that (Ru/Mn)O6 octahedral rotation is no longer detectable at x >= 0.23,
      leading to the tetragonal structure. The magnetization measurements indicate the
      ferromagnetic transition temperature TC decreases from 105 K for x = 0 to 30 K
      for x = 0.41, with the reduced magnetic moment as well. Remarkably, Mn doping
      results in the change of magnetic anisotropy from the easy c axis in x = 0 to the
      easy ab plane seen in x = 0.34 and 0.41. Such change also removes the ab-plane
      metamagnetic transition observed in x = 0. Furthermore, the electrical
      resistivity increases with increasing x showing semiconducting behavior with
      Delta ~ 10 meV for x = 0.34 and 30 meV for x = 0.41. Under applied magnetic
      field, the magnetoresistance exhibits negative and linear field dependence in all
      current and field configurations. These results clearly indicate Sr4(Ru1
      xMnx)3O10 is a novel ferromagnetic semiconductor with exotic magnetotransport
      properties.

PMID- 30190605
TI  - A Multicentric Brazilian Investigative Study of Copy Number Variations in
      Patients with Congenital Anomalies and Intellectual Disability.
AB  - Genomic imbalances are the most common cause of congenital anomalies (CA) and
      intellectual disability (ID). The aims of this study were to identify copy number
      variations (CNVs) in 416 patients with CA and ID from 5 different genetics
      centers within 4 different states by using the Multiplex Ligation-dependent Probe
      Amplification (MLPA) technique and to apply the chromosomal microarray (CMA)
      methodology in selected cases. The samples were analyzed by MLPA kits P064, P036,
      P070 and P250. Positive results were found in 97/416 (23.3%) patients. CMA was
      applied in 14 selected cases. In 6/14 (42.85%) patients, CMA detected other copy
      number variations not detected by the MLPA studies. Although CMA is indispensable
      for genotype refinement, the technique is still unfeasible in some countries as a
      routine analysis due to economic and technical limitations. In these cases,
      clinical evaluation followed by karyotyping and MLPA analysis is a helpful and
      affordable solution for diagnostic purposes.

PMID- 30190607
TI  - Superior lentiviral vectors designed for BSL-0 environment abolish vector
      mobilization.
AB  - Lentiviral vector mobilization following HIV-1 infection of vector-transduced
      cells poses biosafety risks to vector-treated patients and their communities. The
      self-inactivating (SIN) vector design has reduced, however, not abolished
      mobilization of integrated vector genomes. Furthermore, an earlier study
      demonstrated the ability of the major product of reverse transcription, a
      circular SIN HIV-1 vector comprising a single- long terminal repeat (LTR) to
      support production of high vector titers. Here, we demonstrate that configuring
      the internal vector expression cassette in opposite orientation to the LTRs
      abolishes mobilization of SIN vectors. This additional SIN mechanism is in part
      premised on induction of host PKR response to double-stranded RNAs comprised of
      mRNAs transcribed from cryptic transcription initiation sites around 3'SIN-LTR's
      and the vector internal promoter. As anticipated, PKR response following
      transfection of opposite orientation vectors, negatively affects their titers.
      Importantly, shRNA-mediated knockdown of PKR rendered titers of SIN HIV-1 vectors
      comprising opposite orientation expression cassettes comparable to titers of
      conventional SIN vectors. High-titer vectors carrying an expression cassette in
      opposite orientation to the LTRs efficiently delivered and maintained high levels
      of transgene expression in mouse livers. This study establishes opposite
      orientation expression cassettes as an additional PKR-dependent SIN mechanism
      that abolishes vector mobilization from integrated and episomal SIN lentiviral
      vectors.

PMID- 30190609
TI  - One and one is not two: taking a fresh look at membrane interfaces.

PMID- 30190608
TI  - Biocontrol characteristics of the fruit fly pupal parasitoid Trichopria
      drosophilae (Hymenoptera: Diapriidae) emerging from different hosts.
AB  - Trichopria drosophilae (Hymenoptera: Diapriidae) is an important pupal
      endoparasitoid of Drosophila melanogaster Meigen (Diptera: Drosophilidae) and
      some other fruit fly species, such as D. suzukii, a very important invasive and
      economic pest. Studies of T. drosophilae suggest that this could be a good
      biological control agent for fruit fly pests. In this research, we compared the
      parasitic characteristics of T. drosophilae reared in D. melanogaster (TDm) with
      those reared in D. hydei (TDh). TDh had a larger size than TDm. The number of
      maximum mature eggs of a female TDh was 133.6 +/- 6.9, compared with the
      significantly lower value of 104.8 +/- 11.4 for TDm. Mated TDh female wasp
      continuously produced female offspring up to 6 days after mating, compared with
      only 3 days for TDm. In addition, the offspring female ratio of TDh, i.e.,
      82.32%, was significantly higher than that of TDm, i.e., 61.37%. Under starvation
      treatment, TDh survived longer than TDm. TDh also survived longer than TDm at
      high temperatures, such as 37  degrees C, although they both survived well at low
      temperatures, such as 18  degrees C and 4  degrees C. Old-age TDh females
      maintained a high parasitism rate and offspring female ratio, while they were
      declined in old-age TDm. Overall, TDh had an advantage in terms of body size,
      fecundity, stress resistance ability and the parasitism rate compared with TDm.
      Therefore, T. drosophilae from D. hydei could improve biocontrol efficacy with
      enormous economic benefits in the field, especially in the control of many
      frugivorous Drosophilidae species worldwide.

PMID- 30190610
TI  - Correction: Effectiveness of plasma lyso-Gb3 as a biomarker for selecting high
      risk patients with Fabry disease from multispecialty clinics for genetic
      analysis.
AB  - In the above article, we noticed that one female patient in the positive group
      (plasma lyso-Gb3 7.6 ng/ml, alpha-galactosidase A activity 4.9 nmol/h/ml) who
      presented at the neurology clinic was already diagnosed with Fabry disease before
      the current study. We excluded patients with a confirmed diagnosis of Fabry
      disease and those with relatives known to have Fabry disease. To accurately
      describe the information in the current study, we must exclude this patient from
      the analysis. We have accurately revised this information as follows.

PMID- 30190612
TI  - Rare variants in the genetic background modulate cognitive and developmental
      phenotypes in individuals carrying disease-associated variants.
AB  - PURPOSE: To assess the contribution of rare variants in the genetic background
      toward variability of neurodevelopmental phenotypes in individuals with rare copy
      number variants (CNVs) and gene-disruptive variants. METHODS: We analyzed
      quantitative clinical information, exome sequencing, and microarray data from 757
      probands and 233 parents and siblings who carry disease-associated variants.
      RESULTS: The number of rare likely deleterious variants in functionally
      intolerant genes ("other hits") correlated with expression of neurodevelopmental
      phenotypes in probands with 16p12.1 deletion (n=23, p=0.004) and in autism
      probands carrying gene-disruptive variants (n=184, p=0.03) compared with their
      carrier family members. Probands with 16p12.1 deletion and a strong family
      history presented more severe clinical features (p=0.04) and higher burden of
      other hits compared with those with mild/no family history (p=0.001). The number
      of other hits also correlated with severity of cognitive impairment in probands
      carrying pathogenic CNVs (n=53) or de novo pathogenic variants in disease genes
      (n=290), and negatively correlated with head size among 80 probands with 16p11.2
      deletion. These co-occurring hits involved known disease-associated genes such as
      SETD5, AUTS2, and NRXN1, and were enriched for cellular and developmental
      processes. CONCLUSION: Accurate genetic diagnosis of complex disorders will
      require complete evaluation of the genetic background even after a candidate
      disease-associated variant is identified.

PMID- 30190611
TI  - Expanding the clinical phenotype of individuals with a 3-bp in-frame deletion of
      the NF1 gene (c.2970_2972del): an update of genotype-phenotype correlation.
AB  - PURPOSE: Neurofibromatosis type 1 (NF1) is characterized by a highly variable
      clinical presentation, but almost all NF1-affected adults present with cutaneous
      and/or subcutaneous neurofibromas. Exceptions are individuals heterozygous for
      the NF1 in-frame deletion, c.2970_2972del (p.Met992del), associated with a mild
      phenotype without any externally visible tumors. METHODS: A total of 135
      individuals from 103 unrelated families, all carrying the constitutional NF1
      p.Met992del pathogenic variant and clinically assessed using the same
      standardized phenotypic checklist form, were included in this study. RESULTS:
      None of the individuals had externally visible plexiform or histopathologically
      confirmed cutaneous or subcutaneous neurofibromas. We did not identify any
      complications, such as symptomatic optic pathway gliomas (OPGs) or symptomatic
      spinal neurofibromas; however, 4.8% of individuals had nonoptic brain tumors,
      mostly low-grade and asymptomatic, and 38.8% had cognitive impairment/learning
      disabilities. In an individual with the NF1 constitutional c.2970_2972del and
      three astrocytomas, we provided proof that all were NF1-associated tumors given
      loss of heterozygosity at three intragenic NF1 microsatellite markers and
      c.2970_2972del. CONCLUSION: We demonstrate that individuals with the NF1
      p.Met992del pathogenic variant have a mild NF1 phenotype lacking clinically
      suspected plexiform, cutaneous, or subcutaneous neurofibromas. However, learning
      difficulties are clearly part of the phenotypic presentation in these individuals
      and will require specialized care.

PMID- 30190616
TI  - Reopening the dialogue.

PMID- 30190614
TI  - Urinary neopterin levels increase and predict survival during a respiratory
      outbreak in wild chimpanzees (Tai National Park, Cote d'Ivoire).
AB  - Monitoring immune system activation of wild animals has garnered increasing
      interest within the field of ecological immunology, leading to an urgent need for
      non-invasive biomarkers measuring these changes. Urinary neopterin, a marker of
      the cell-mediated immune response, is validated as an immune-related biomarker in
      captive and laboratory animals. However, wild animals naturally host higher and
      chronic pathogen loads. Therefore, detection and quantification of additional
      infections via neopterin might not be possible against the background of a
      chronically challenged immune system. To assess the suitability of urinary
      neopterin in wild animals, we measured neopterin corrected for specific gravity
      with an enzyme immunoassay in 185 samples collected before, during and after a
      respiratory disease outbreak in 28 individuals from a group of wild chimpanzees
      (Tai National Park, Cote d'Ivoire). Urinary neopterin levels were significantly
      higher during periods when individuals showed respiratory symptoms versus before
      and after the outbreak. Furthermore, urinary neopterin levels were significantly
      higher in individuals that died, with higher levels already apparent before the
      outbreak, suggesting individuals may have an already activated immune system.
      Measuring urinary neopterin levels, with other biomarkers of energetic condition,
      stress challenges, and reproduction will contribute towards a deeper
      understanding of life-history trade-offs in wild animals.

PMID- 30190617
TI  - Paving the way to single-molecule protein sequencing.
AB  - Proteins are major building blocks of life. The protein content of a cell and an
      organism provides key information for the understanding of biological processes
      and disease. Despite the importance of protein analysis, only a handful of
      techniques are available to determine protein sequences, and these methods face
      limitations, for example, requiring a sizable amount of sample. Single-molecule
      techniques would revolutionize proteomics research, providing ultimate
      sensitivity for the detection of low-abundance proteins and the realization of
      single-cell proteomics. In recent years, novel single-molecule protein sequencing
      schemes that use fluorescence, tunnelling currents and nanopores have been
      proposed. Here, we present a review of these approaches, together with the first
      experimental efforts towards their realization. We discuss their advantages and
      drawbacks, and present our perspective on the development of single-molecule
      protein sequencing techniques.

PMID- 30190613
TI  - Regionally specific TSC1 and TSC2 gene expression in tuberous sclerosis complex.
AB  - Tuberous sclerosis complex (TSC), a heritable neurodevelopmental disorder, is
      caused by mutations in the TSC1 or TSC2 genes. To date, there has been little
      work to elucidate regional TSC1 and TSC2 gene expression within the human brain,
      how it changes with age, and how it may influence disease. Using a publicly
      available microarray dataset, we found that TSC1 and TSC2 gene expression was
      highest within the adult neo-cerebellum and that this pattern of increased
      cerebellar expression was maintained throughout postnatal development. During mid
      gestational fetal development, however, TSC1 and TSC2 expression was highest in
      the cortical plate. Using a bioinformatics approach to explore protein and
      genetic interactions, we confirmed extensive connections between TSC1/TSC2 and
      the other genes that comprise the mammalian target of rapamycin (mTOR) pathway,
      and show that the mTOR pathway genes with the highest connectivity are also
      selectively expressed within the cerebellum. Finally, compared to age-matched
      controls, we found increased cerebellar volumes in pediatric TSC patients without
      current exposure to antiepileptic drugs. Considered together, these findings
      suggest that the cerebellum may play a central role in TSC pathogenesis and may
      contribute to the cognitive impairment, including the high incidence of autism
      spectrum disorder, observed in the TSC population.

PMID- 30190615
TI  - Pro inflammatory stimuli enhance the immunosuppressive functions of adipose
      mesenchymal stem cells-derived exosomes.
AB  - The predominant mechanism by which adipose mesenchymal stem cells (AMSCs)
      participate to tissue repair is through a paracrine activity and their
      communication with the inflammatory microenvironment is essential part of this
      process. This hypothesis has been strengthened by the recent discovery that stem
      cells release not only soluble factors but also extracellular vesicles, which
      elicit similar biological activity to the stem cells themselves. We demonstrated
      that the treatment with inflammatory cytokines increases the immunosuppressive
      and anti-inflammatory potential of AMSCs-derived exosomes, which acquire the
      ability to shift macrophages from M1 to M2 phenotype by shuttling miRNA
      regulating macrophages polarization. This suggests that the immunomodulatory
      properties of AMSCs-derived exosomes may be not constitutive, but are instead
      induced by the inflammatory microenvironment.

PMID- 30190618
TI  - The ten decrees of nanomaterials regulations.

PMID- 30190619
TI  - Hidden interfaces revealed on an atomistic level.

PMID- 30190621
TI  - A single object rotating.

PMID- 30190622
TI  - Boost microbiota studies.

PMID- 30190623
TI  - One and the same.

PMID- 30190624
TI  - Seeing through the noise.

PMID- 30190620
TI  - Minimum information reporting in bio-nano experimental literature.
AB  - Studying the interactions between nanoengineered materials and biological systems
      plays a vital role in the development of biological applications of
      nanotechnology and the improvement of our fundamental understanding of the bio
      nano interface. A significant barrier to progress in this multidisciplinary area
      is the variability of published literature with regards to characterizations
      performed and experimental details reported. Here, we suggest a 'minimum
      information standard' for experimental literature investigating bio-nano
      interactions. This standard consists of specific components to be reported,
      divided into three categories: material characterization, biological
      characterization and details of experimental protocols. Our intention is for
      these proposed standards to improve reproducibility, increase quantitative
      comparisons of bio-nano materials, and facilitate meta analyses and in silico
      modelling.

PMID- 30190625
TI  - Formation and Destruction of SiS in Space.
AB  - The presence of SiS in space seems to be restricted to a few selected types of
      astronomical environments. It is long known to be present in circumstellar
      envelopes around evolved stars and it has also been detected in a handful of star
      forming regions with evidence of outflows, like Sgr B2, Orion KL and more
      recently L1157-B1. The kinetics of reactions involving SiS is very poorly known
      and here we revisit the chemistry of SiS in space by studying some potentially
      important reactions of formation and destruction of this molecule. We calculated
      ab initio potential energy surfaces of the SiOS system and computed rate
      coefficients in the temperature range 50-2500 K for the reaction of destruction
      of SiS, in collisions with atomic O, and of its formation, through the reaction
      between Si and SO. We find that both reactions are rapid, with rate coefficients
      of a few times 10-10 cm3 s-1, almost independent of temperature. In the reaction
      between Si and SO, SiO production is 5-7 times more efficient than SiS formation.
      The reaction of SiS with O atoms can play an important role in destroying SiS in
      envelopes around evolved stars. We built a simple chemical model of a postshock
      gas to study the chemistry of SiS in protostellar outflows and we found that SiS
      forms with a lower abundance and later than SiO, that SiS is efficiently
      destroyed through reaction with O, and that the main SiS-forming reactions are Si
      + SO and Si + SO2.

PMID- 30190627
TI  - Thoracic lymph node station recognition on CT images based on automatic anatomy
      recognition with an optimal parent strategy.
AB  - Currently, there are many papers that have been published on the detection and
      segmentation of lymph nodes from medical images. However, it is still a
      challenging problem owing to low contrast with surrounding soft tissues and the
      variations of lymph node size and shape on computed tomography (CT) images. This
      is particularly very difficult on low-dose CT of PET/CT acquisitions. In this
      study, we utilize our previous automatic anatomy recognition (AAR) framework to
      recognize the thoracic-lymph node stations defined by the International
      Association for the Study of Lung Cancer (IASLC) lymph node map. The lymph node
      stations themselves are viewed as anatomic objects and are localized by using a
      one-shot method in the AAR framework. Two strategies have been taken in this
      paper for integration into AAR framework. The first is to combine some lymph node
      stations into composite lymph node stations according to their geometrical
      nearness. The other is to find the optimal parent (organ or union of organs) as
      an anchor for each lymph node station based on the recognition error and thereby
      find an overall optimal hierarchy to arrange anchor organs and lymph node
      stations. Based on 28 contrast-enhanced thoracic CT image data sets for model
      building, 12 independent data sets for testing, our results show that thoracic
      lymph node stations can be localized within 2-3 voxels compared to the ground
      truth.

PMID- 30190626
TI  - Chemistry below graphene: decoupling epitaxial graphene from metals by potential
      controlled electrochemical oxidation.
AB  - While high-quality defect-free epitaxial graphene can be efficiently grown on
      metal substrates, strong interaction with the supporting metal quenches its
      outstanding properties. Thus, protocols to transfer graphene to insulating
      substrates are obligatory, and these often severely impair graphene properties by
      the introduction of structural or chemical defects. Here we describe a simple and
      easily scalable general methodology to structurally and electronically decouple
      epitaxial graphene from Pt(111) and Ir(111) metal surfaces. A multi-technique
      characterization combined with ab-initio calculations was employed to fully
      explain the different steps involved in the process. It was shown that, after a
      controlled electrochemical oxidation process, a single-atom thick metal-hydroxide
      layer intercalates below graphene, decoupling it from the metal substrate. This
      decoupling process occurs without disrupting the morphology and electronic
      properties of graphene. The results suggest that suitably optimized
      electrochemical treatments may provide effective alternatives to current transfer
      protocols for graphene and other 2D materials on diverse metal surfaces.

PMID- 30190628
TI  - Automatic Anatomy Recognition using Neural Network Learning of Object
      Relationships via Virtual Landmarks.
AB  - The recently developed body-wide Automatic Anatomy Recognition (AAR) methodology
      depends on fuzzy modeling of individual objects, hierarchically arranging
      objects, constructing an anatomy ensemble of these models, and a dichotomous
      object recognition-delineation process. The parent-to-offspring spatial
      relationship in the object hierarchy is crucial in the AAR method. We have found
      this relationship to be quite complex, and as such any improvement in capturing
      this relationship information in the anatomy model will improve the process of
      recognition itself. Currently, the method encodes this relationship based on the
      layout of the geometric centers of the objects. Motivated by the concept of
      virtual landmarks (VLs), this paper presents a new one-shot AAR recognition
      method that utilizes the VLs to learn object relationships by training a neural
      network to predict the pose and the VLs of an offspring object given the VLs of
      the parent object in the hierarchy. We set up two neural networks for each parent
      offspring object pair in a body region, one for predicting the VLs and another
      for predicting the pose parameters. The VL-based learning/prediction method is
      evaluated on two object hierarchies involving 14 objects. We utilize 54 computed
      tomography (CT) image data sets of head and neck cancer patients and the
      associated object contours drawn by dosimetrists for routine radiation therapy
      treatment planning. The VL neural network method is found to yield more accurate
      object localization than the currently used simple AAR method.

PMID- 30190630
TI  - Hierarchical model-based object localization for auto-contouring in head and neck
      radiation therapy planning.
AB  - Segmentation of organs at risk (OARs) is a key step during the radiation therapy
      (RT) treatment planning process. Automatic anatomy recognition (AAR) is a
      recently developed body-wide multiple object segmentation approach, where
      segmentation is designed as two dichotomous steps: object recognition (or
      localization) and object delineation. Recognition is the high-level process of
      determining the whereabouts of an object, and delineation is the meticulous low
      level process of precisely indicating the space occupied by an object. This study
      focuses on recognition. The purpose of this paper is to introduce new features of
      the AAR-recognition approach (abbreviated as AAR-R from now on) of combining
      texture and intensity information into the recognition procedure, using the
      optimal spanning tree to achieve the optimal hierarchy for recognition to
      minimize recognition errors, and to illustrate recognition performance by using
      large-scale testing computed tomography (CT) data sets. The data sets pertain to
      216 non-serial (planning) and 82 serial (re-planning) studies of head and neck
      (H&N) cancer patients undergoing radiation therapy, involving a total of ~2600
      object samples. Texture property "maximum probability of occurrence" derived from
      the co-occurrence matrix was determined to be the best property and is utilized
      in conjunction with intensity properties in AAR-R. An optimal spanning tree is
      found in the complete graph whose nodes are individual objects, and then the tree
      is used as the hierarchy in recognition. Texture information combined with
      intensity can significantly reduce location error for gland-related objects
      (parotid and submandibular glands). We also report recognition results by
      considering image quality, which is a novel concept. AAR-R with new features
      achieves a location error of less than 4 mm (~1.5 voxels in our studies) for good
      quality images for both serial and non-serial studies.

PMID- 30190629
TI  - Auto-contouring via Automatic Anatomy Recognition of Organs at Risk in Head and
      Neck Cancer on CT images.
AB  - Contouring of the organs at risk is a vital part of routine radiation therapy
      planning. For the head and neck (H&N) region, this is more challenging due to the
      complexity of anatomy, the presence of streak artifacts, and the variations of
      object appearance. In this paper, we describe the latest advances in our
      Automatic Anatomy Recognition (AAR) approach, which aims to automatically contour
      multiple objects in the head and neck region on planning CT images. Our method
      has three major steps: model building, object recognition, and object
      delineation. First, the better-quality images from our cohort of H&N CT studies
      are used to build fuzzy models and find the optimal hierarchy for arranging
      objects based on the relationship between objects. Then, the object recognition
      step exploits the rich prior anatomic information encoded in the hierarchy to
      derive the location and pose for each object, which leads to generalizable and
      robust methods and mitigation of object localization challenges. Finally, the
      delineation algorithms employ local features to contour the boundary based on
      object recognition results. We make several improvements within the AAR
      framework, including finding recognition-error-driven optimal hierarchy, modeling
      boundary relationships, combining texture and intensity, and evaluating object
      quality. Experiments were conducted on the largest ensemble of clinical data sets
      reported to date, including 216 planning CT studies and over 2,600 object
      samples. The preliminary results show that on data sets with minimal (<4 slices)
      streak artifacts and other deviations, overall recognition accuracy reaches 2
      voxels, with overall delineation Dice coefficient close to 0.8 and Hausdorff
      Distance within 1 voxel.

PMID- 30190631
TI  - Ischiofemoral hip ligament reconstructions for recurrent posterior total hip
      joint dislocations.
AB  - Objective: Recurrent dislocations of a total hip joint replacement are a
      difficult problem to address. We present a technique for reconstructing the
      ischiofemoral ligament of the hip to prevent recurrent posterior dislocations.
      Methods: This is a case series of 5 patients with a reconstruction performed
      using either a bone-patellar tendon-bone graft autograft or allograft. Results:
      At an average follow up of 47 months following the reconstruction, there were no
      redislocations. Conclusion: Ischiofemoral hip ligament reconstruction is a viable
      technique in addressing recurrent dislocations of total hip joint replacements.

PMID- 30190632
TI  - The Morel-Lavallee lesion and its management: A review of the literature.
AB  - Background: Morel-Lavallee lesions can occur in polytrauma patients. Post
      operative seroma is more frequently encountered, holds many pathological
      similarities with MLLs and continues to challenge plastic surgeons. We aimed to
      provide a comprehensive overview of MLLs to increase awareness of optimum
      treatment options amongst plastic surgery teams, and to provide a management
      algorithm that may also be applied to post-operative seromas. Methods: PubMed,
      Google Scholar and the Cochrane Library were searched using the terms "Morel
      Lavallee", "management" and "treatment", which yielded 52 results. One reviewer
      screened titles and abstracts for relevance. Seventeen full text articles were
      retrieved. Review of reference lists provided a further three articles for
      inclusion. Findings: Morel-Lavallee lesions (MLLs) represent closed injuries with
      internal degloving of superficial soft tissues from fascial layers. Main causes
      of MLLs include high-energy, blunt force trauma or crush injuries. They are
      commonly found overlying the greater trochanter. MLLs should be actively looked
      for when treating patients with pelvic trauma. MRI is the investigation of
      choice. Currently no guidelines for the management of MLLs exist. Compression
      bandaging, percutaneous aspiration, sclerodesis and mass resection have all been
      utilised. Conclusions: Our algorithm recommends avoidance of conservative
      management. For chronic lesions, percutaneous aspiration should not be used in
      isolation. Sclerodesis using doxycycline is appropriate for lesions up to 400 ml,
      where evidence suggests high degrees of efficacy. Larger lesions should be
      treated with open surgery. Quilting sutures, curettage and low suction drains are
      useful adjuncts. We hypothesise this algorithm would also be effective for post
      operative seromas.

PMID- 30190633
TI  - Revision shoulder arthroplasty: Patient-reported outcomes vary according to the
      etiology of revision.
AB  - Background: The study evaluates patient-reported outcomes in revision shoulder
      arthroplasty (RevSA) according to etiology. Methods: Twenty-three consecutive
      RevSA (minimum 2-year follow-up) were retrospectively reviewed. Patient-reported
      outcome (PRO) scores and range of motion were compared by the type of revision
      procedure and indication. Results: EQ5D-QOL, VAS-pain, ASES, and forward
      elevation improved after RevSA. The infection group had least improvements.
      Revision to a reverse total shoulder arthroplasty (RTSA) demonstrated the most
      improvement in VAS-pain, forward elevation, and ASES. Conclusions: Revision to
      RTSA significantly improved PRO scores compared to hemi- or total shoulder
      arthroplasty. RevSA for infection demonstrated the least improvement in outcomes.

PMID- 30190634
TI  - Effect of multiple hereditary exostoses on sports activity in children.
AB  - Objective: The purpose of this clinical case-control study was to assess the
      level of sports activity in children with hereditary multiple exostoses (HME) and
      to compare with the degree of physical activity in children of the same age
      without pathology. Methods: A case-control study was designed. Cases were drawn
      from children with HME diagnosed on the basis of clinical and radiographic
      evaluation with an age less then 12 years. Controls were chosen from a group of
      children with the same age and a negative family history for HME. All patients
      and controls were completed with the help of parents using the following
      evaluations: Tegner Activity Level Scale and University of California Los Angeles
      (UCLA) activity scale. Results: A total of 154 individuals participated (54 cases
      and 100 controls). In the case groups, the mean age was 9.07; the mean number of
      exostoses resulted 29.51, while the mean value of UCLA and Tegner score resulted
      respectively 6.04 and 5.09. In the controls, the mean age was 8.88; mean UCLA and
      Tegner resulted respectively 7.17 and 5.64. Comparing the two groups, the only
      difference was between UCLA score (p = 0.0053). Moreover, comparing the results
      between female children affected by HME and female controls, we found a
      significant difference as regards UCLA score (p = 0.0045). Conclusion: Children
      affected by HME reported lower sports activity, in particular as regards female
      patients. Moreover, physical activity is not correlated with any other
      independent factor leading different patients to a similar level of ability in
      performing sport. Study design: Level III - Case Control Study.

PMID- 30190635
TI  - Sentinel sign in standalone anterior cervical fusion: Outcomes and fusion rate.
AB  - Background: The authors aim to demonstrate the feasibility, outcomes and fusion
      rate of a standalone PEEK cage in the outpatient setting. Methods: 48 consecutive
      patients undergoing standalone ACDF (S-ACDF) (Group 1) were compared to control
      group of 49 patients who had ACDF with ACP (Group 2). Results: Analysis of follow
      up at the one year period postoperative outcomes between groups 1 and 2
      demonstrated no intergroup statistical significant difference in VAS neck, arm
      and NDI scores p = 0.414, 0.06 and p = 0.328 respectively. Conclusion: We
      conclude that S-ACDF can be safely done in an ambulatory surgery center with
      satisfactory clinical and patient-reported outcomes.

PMID- 30190636
TI  - Prevalence of lipid abnormalities and cholesterol target value attainment in
      Egyptian patients presenting with an acute coronary syndrome.
AB  - Background: Effective management of hyperlipidemia is of utmost importance for
      prevention of recurring cardiovascular events after an acute coronary syndrome
      (ACS). Indeed, guidelines recommend a low-density lipoprotein cholesterol (LDL-C)
      level of <70 mg/dL for such patients. The Dyslipidemia International Study II
      (DYSIS II) - Egypt was initiated in order to quantify the prevalence and extent
      of hyperlipidemia in patients presenting with an ACS in Egypt. Methods: In this
      prospective, observational study, we documented patients presenting with an ACS
      at either of two participating centers in Egypt between November 2013 and
      September 2014. Individuals were included if they were over 18 years of age, had
      a full lipid profile available (recorded within 24 h of admission), and had
      either been taking lipid-lowering therapy (LLT) for >=3 months at time of
      enrollment or had not taken LLT. Data regarding lipid levels and LLT were
      recorded on admission to hospital and at follow-up 4 months later. Results: Of
      the 199 patients hospitalized for an ACS that were enrolled, 147 were on LLT at
      admission. Mean LDL-C at admission was 127.1 mg/dL, and was not significantly
      different between users and non-users of LLT. Only 4.0% of patients had an LDL-C
      level of <70 mg/dL, with the median distance to this target being 61.0 mg/dL. For
      the patients with LDL-C information available at both admission and follow-up,
      LDL-C target attainment rose from 2.8% to 5.6%. Most of the LLT-treated patients
      received statin monotherapy (98.6% at admission and 97.3% at follow-up), with the
      mean daily statin dose (normalized to atorvastatin) increasing from admission (30
      mg/day) to follow-up (42 mg/day). Conclusions: DYSIS II revealed alarming LDL-C
      goal attainment, with none of the patients with follow-up information available
      reaching the target of LDL-C <70 mg/dL, either at hospital admission or 4 months
      after their ACS event. Improvements in guideline adherence are urgently needed
      for reducing the burden of cardiovascular disease in Egypt. Strategies include
      the effective use of statins at high doses, or combination with other agents
      recommended by guidelines.

PMID- 30190637
TI  - Incidence and predictors of bleeding among Egyptian patients presenting with
      acute coronary syndrome: Using CRUSADE risk score.
AB  - Background: Early invasive strategies; in management of acute coronary syndrome;
      has led to improvement of patient outcomes. However, these invasive therapies
      have their own risks, namely bleeding and blood transfusion.The aim of this study
      was to determine the incidence of bleeding, its location and severity among the
      study population, to correlate between the patients' characteristics and the risk
      profile of the patients based upon the CRUSADE risk score and increased bleeding
      events, and lastly; to identify the predictors of increased bleeding risk among
      Egyptian patients who presented with acute coronary syndrome. Methods: The study
      had included eight hundred and twenty-three patients referred to coronary care
      unit (CCU), to (Ain Shams University hospital, Specialized Ain Shams hospital,
      and 6th October insurance hospital) with diagnosis of Acute Coronary Syndrome
      "ACS" within a period from 1/2014 till 7/2014, and they were followed up for
      additional three months following discharge with assessment of their bleeding
      risk and risk scores. Results: More bleeding events had been witnessed among the
      study population who were older, diabetics, had renal impairment, had peripheral
      vascular disease, had congestive heart failure picture at presentation; more
      among female sex category and more among patients receiving GPIIbIIIa
      antagonists. Those bleeding events had been experienced during hospital stay.
      Conclusion: Risk of bleeding can be evaluated using a simple risk score in both
      STEMI & NSTEMI patients, and across anti-coagulant strategies, providing
      important prognostic information. Variability in the rates of bleeding is likely
      based on differences in baseline characteristics, comorbidities, and invasive
      treatment strategies rather than specific anti-coagulation regimens. Patients at
      highest risk of bleeding are also at highest risk of ischaemia and thrombotic
      complications. Thus higher risk patients need a more careful treatment approach
      to maximize the efficacy of therapy and to reduce thrombotic risk while reducing
      the bleeding risk.

PMID- 30190639
TI  - Right ventricular function in patients presenting with non-ST-segment elevation
      myocardial infarction undergoing an invasive approach.
AB  - Background: Right ventricular involvement in ST segment elevation myocardial
      infarction (STEMI) entails an increased morbidity and mortality. However, very
      scarce data is present on its affection in the setting of non-ST segment
      elevation myocardial infarction (NSTEMI). Aim: To assess the affection of right
      ventricular function in patients presenting with NSTEMI undergoing an invasive
      procedure. Subjects and methods: One hundred and fifty patients admitted with a
      first NSTEMI and eligible for reperfusion therapy via invasive percutaneous
      coronary intervention. These patients were divided in two groups; group A
      including patients with normal RV function, and group B including patients with
      impaired RV function as diagnosed by tricuspid annular plane systolic excursion
      (TAPSE) cutoff value < 17 mm. All patients underwent angioplasty and were
      followed up in-hospital and for 3 months. Results: RV dysfunction occurred in
      ninety-five (61.3%) patients of the study population. Significant improvement
      occurred to TAPSE after 3 months in comparison to TAPSE at baseline (15.45 +/-
      3.21 versus 17.09 +/- 4.17 mm). Those with impaired RV function showed
      improvement of TAPSE after three months as compared to baseline (13.62 +/- 2.58
      vs 17.16 +/- 3.64 p = 0.008). Multivariate analysis determined the independent
      predictors of RV dysfunction as RVEDD > 26 mm, RVFAC < 35%, RAA > 20 cm2, and
      TAPSE < 17 mm. Conclusion: RV dysfunction is not uncommon in NSTEMI when using
      the definition of TAPSE < 17 mm. Following up RV function by TAPSE, showed
      significant improvement after 3 months with successful PCI as compared to
      baseline. We recommend assessing and following up RV function in all patients
      admitted with a NSTEMI.

PMID- 30190638
TI  - Death anxiety in patients with myocardial infarction or cancer.
AB  - Objective: The aim of this study was to find out the level of death anxiety among
      3 groups: patients with acute myocardial infarction, patients with cancer and
      healthy individuals in two training and research hospitals; also to evaluate its
      relationship with several sociodemographic and clinical variables. Materials and
      method: This study was conducted with one hundred and eighty persons (108 male,
      72 female) who have been referred to cardiology or oncology departments and the
      healthy individuals. Participants completed sociodemographic and clinical data
      form, State and Trait Anxiety Inventory (STAI-I, STAI-II), Thorson Powell Death
      Anxiety Scale (TPDAS), Death Depression Scale (DDS). Results: Participants
      included in the present study were 40% female with an average age of 53.48 for
      whole group. The mean TPDAS score for patients with AMI was 51.60 +/- 16.40, for
      patients with cancer 37.10 +/- 10.23 and for healthy individuals 43.40 +/- 13.35.
      In AMI group there were positive correlations between STAI-I and TPDAS, DDS
      scores and also between STAI-II and DDS. In cancer group positive correlations
      were between STAI-I, II and TPDAS, DDS. TPDAS and DDS were positively correlated
      in all three groups. Women and participants who were unemployed scored higher on
      DDS. Conclusion: In this study patients with AMI had higher death anxiety than
      patients with cancer or healthy individuals. Generally death anxiety was related
      with education, employment and socioeconomic status. Prospective studies
      carefully searching for different variables in different medical groups would
      reveal and help us to understand the importance of death anxiety and its impact
      on courses of physical and mental disorders.

PMID- 30190640
TI  - Clinical role of serum Copeptin in acute coronary syndrome.
AB  - Objective: To assess the role of Copeptin in diagnosis of acute myocardial
      infarction in troponin-blind period. Subjects and methods: This study was
      conducted on 40 patients who presented to emergency department complaining of
      chest pain and were highly suspicious to have acute cardiac ischemia, in addition
      to 10 subjects serving as a healthy control group. Blood samples were collected
      for determination of CK-MB, cTnI and Copeptin. These were measured twice (in
      patients' group); at 3 h and then at 6-9 h from admission time. Results: The
      first sample revealed a non-significant difference between UA group and AMI group
      as regards CKMB and troponin, however, high significant difference was found as
      regards Copeptin (Z = 5.29, P < 0.001). Moreover, ROC curve analysis of serum
      Copeptin for discriminating AMI group from UA group in the first sample showed
      diagnostic sensitivity and specificity of 100%. In conclusion: Determination of
      copeptin in early diagnosis of AMI has diagnostic value being superior to a
      conventional cTn-I within the first three hours after acute chest pain.

PMID- 30190641
TI  - Impact of fractional flow reserve on decision-making in daily clinical practice:
      A single center experience in Egypt.
AB  - Background: Fractional flow reserve (FFR) is the reference standard for the
      assessment of the functional significance of coronary artery stenoses, but
      remains underutilized. Our aims were to study whether FFR changed the decision
      for treatment of intermediate coronary lesions and to assess the clinical outcome
      in the deferred and intervention groups. Methods: In this retrospective study,
      coronary angiograms of patients with moderately stenotic lesions (40-70%) for
      which FFR was performed were re-analyzed by three experienced interventional
      cardiologists (blinded to FFR results) to determine its angiographic significance
      and whether to defer or perform an intervention. Results: We revised 156
      equivocal lesions of 151 patients. The clinical presentation were stable angina
      (65.6%) and acute coronary syndrome in (34.4%). All reviewers had concordant
      agreement to do PCI in 59 (37.8%) lesions based on angiographic assessment.
      Interestingly 23 (39%) of these lesions were functionally non-significant by FFR.
      The reviewers agreed to defer 97 (62.2%) lesions, however, 32 (33%) of these
      lesions were functionally significant by FFR and necessitated PCI. MACE were
      similar in both groups (1.5% vs 2.4%, p = 1.0). Conclusion: Mismatches between
      visually- and FFR- estimated significance of intermediate coronary stenosis are
      frequently encountered across a wide spectrum of clinical presentations. FFR
      leads to a change in decision for coronary intervention. The clinical and cost
      implications of such changes-in areas with limited resources- needs further
      evaluation.

PMID- 30190642
TI  - Retinal fluorescein angiography: A sensitive and specific tool to predict
      coronary slow flow.
AB  - Background: Obstructive coronary artery disease (OCAD) and coronary slow flow
      (CSF) are frequent angiographic findings for patients that have chest pain and
      require frequent hospital admission. The retina provides a window for detecting
      changes in microvasculature relating to the development of cardiovascular
      diseases such as arterial hypertension or coronary heart disease. Objectives: To
      assess the coronary and ocular circulations in patients with CSF and those with
      obstructive coronary artery disease. Methods: A prospective study was conducted
      over 3.5 years, included a total of 105 subjects classified to 4 groups: Group I
      (OCAD): Included 30 patients with obstructive coronary artery disease, group II
      (CSF): Included 30 patients with coronary slow-flow, group III (Control 1):
      Included 30 healthy control persons and group IV (Control 2): Included 15
      patients indicated for coronary angiography that proved normal. All participants
      were subjected to coronary angiography (except control group 1), ophthalmic
      artery Doppler for measuring Pulsatility index (PI) and resistivity index (RI)
      and Fluorescence angiography of retinal vessels. Results: Patients with CSF
      showed slow flow retinal circulation (microcirculation) evidenced by prolonged
      fluorescein angiography (Arm-retina time [ART] & Arterio-venous Transit time
      [AVTT]). Ophthalmic artery Doppler measurements (RI & PI) were significantly
      delayed in OCAD and CSF patients. There was significant positive correlation
      between TIMI frame count in all subjects and ART, AVTT, PI, RI and Body Mass
      Index. Using ART cutoff value of >16 s predicted CSF with sensitivity and
      specificity of 100%, meanwhile AVTT of >2 s predicted CSF with a sensitivity
      96.7% and specificity of 93.3. Conclusion: Both delayed arm-retina time and
      retinal arterio-venous transit times can accurately predict coronary slow-flow.

PMID- 30190643
TI  - Assessment of right ventricular function by echocardiography in patients with
      chronic heart failure.
AB  - Background: The main focus of most of the studies in heart failure (HF) is the
      assessment of the left ventricular functions, while the right ventricle was much
      less studied. Much of this neglect is due to the complexity of anatomy and
      physiology of the right ventricle which are considered challenges during
      assessment of RV. Objective: [1] To review the alterations of right ventricular
      dimensions & function associated with chronic heart failure. [2] To predict the
      prevalence of right ventricular systolic dysfunction in patients with chronic
      heart failure, based on echocardiographic parameters. Methods: 100 chronic left
      sided heart failure patients with LVEF less than 40% were evaluated in Ain Shams
      University hospitals from April 2015 to March 2016. All patients were subjected
      to full history taking & clinical evaluation. ECG was done mainly to exclude
      presence of ischemic heart disease. Complete trans-thoracic echocardiography
      study was done for assessment of [B] Left ventricular dimensions, systolic and
      diastolic functions [B] Assessment of the right side of the heart: [1]
      Measurement of the right ventricular dimensions [basal - mid cavity and the
      longitudinal diameters]. [2] Right ventricular area and calculation of the
      fractional area change (FAC). [3] Tricuspid annular plane systolic excursion
      (TAPSE). [4] Tissue Doppler derived tricuspid lateral annular systolic velocity
      (S' wave velocity). [5] Tissue Doppler derived Myocardial Performance Index (MPI)
      (Tei index). [6] Grading of tricuspid regurgitation severity, and assessment of
      right ventricular systolic pressure. Results: Right ventricle was dilated at the
      basal level in 36% of the studied patients & at the mid cavity level in 23% of
      the patients. Longitudinal RV diameter was enlarged in 20% of the patients.Right
      ventricular systolic dysfunction was found in 36% of patients with DCM in the
      current study. Patients who had right ventricular systolic dysfunction had
      significantly higher incidence of elevated JVP, significantly lower EF and
      significantly higher grade of LV Diastolic dysfunction. They showed significantly
      larger RV dimensions at different levels, significantly worse degree of TR and
      significantly higher mean value of RVSP. Conclusions: The occurrence of right
      ventricular systolic dysfunction in patients with DCM is common [Approaching 40%
      in this study] and is independent of age and sex, and is proportionate to the
      degree of LV dilatation, and EF impairment.

PMID- 30190644
TI  - Prevalence of P wave dispersion and interatrial block in patients with systolic
      heart failure and their relationship with functional status, hospitalization and
      one year mortality.
AB  - Background and objectives: P-wave dispersion (PWD) and Interatrial block (IAB)
      are common in heart failure (HF), and could be associated with adverse cardiac
      events. We aimed to assess the prevalence of PWD and IAB and their relationship
      with functional status, hospitalization and mortality rate in patients with
      systolic HF. Methods: We enrolled 110 HF patients in sinus rhythm & LVEF <50%.
      Patients had undergone clinical evaluation, 6 min walking test (6MWT), 12-lead
      electrocardiography (ECG), 24-h Holter ECG & echocardiogram. Hospitalization and
      mortality rate were followed-up for one year. PWD was defined as the difference
      between maximum & minimum P-wave duration >40 ms. IAB was defined as maximum P
      duration >110 ms. Measurements were done by 2 blinded investigators using a
      caliber, a ruler and a magnifying lens. Results: Mean age was 58.9 +/- 9.7 years
      and 67.3% were males. Prevalence of PWD and IAB was 68.2% and 57.3%,
      respectively. Patients with PWD showed these features: 84% in NYHA class III or
      IV HF, 77.4% had LVEF <35%, 78.7% had paroxysmal Atrial Fibrillation (AF) and
      89.4% couldn't complete >200 m (m) in 6MWT. Patients with PWD had more
      hospitalizations (72% vs 28.6%, P value <0.02) and higher 1-year mortality rate
      (20% vs 8.6%, P value <0.04) than patients without PWD. Likewise, patients with
      IAB had nearly similar clinical features, hospitalization and mortality as
      patients with PWD. Conclusion: PWD and IAB are prevalent in patients with
      systolic HF and they are significantly associated with low LVEF, paroxysmal AF,
      poor functional capacity, hospitalization and mortality rate.

PMID- 30190646
TI  - Mitral leaflet separation index. An easy two dimensional echocardiography
      technique for assessment of mitral valve area before and after percutaneous
      balloon mitral valvuloplasty.
AB  - Aim: To evaluate the reliability of the mitral leaflet separation (MLS) index
      against the traditional echocardiographic methods in measuring mitral valve area
      (MVA) pre and post percutaneous balloon mitral valvuloplasty (PBMV). Methods:
      Ninety patients suffering symptomatic moderate to severe MS underwent PBMV at Ain
      Shams University Hospital in cardiology department. Seventy of the patients were
      females representing 77.8% and 20 were males representing 22.2%. Their age ranged
      from 22 to 56 years. All patients were subjected to full transthoracic
      echocardiography (TTE) examination pre and post PBMV. MLS index was introduced as
      a comparative parameter with traditional echocardiographic methods for assessment
      of MVA, measuring average of distance between tips of MV leaflets in parasternal
      long axis and four chamber two dimensional echocardiographic views. Results: MVA
      increased from 0.95 +/- 0.28 to 2.21 +/- 0.41 cm2 (P=0.001) using 2D planimetry;
      and increased from 0.93 +/- 0.23 to 2.21 +/- 0.46 cm2 (P= 0.0011) by pressure
      half time method (PHT). MLS index was correlated with MVA by 2D planimetry pre
      and post PBMV (r=0.453) and (r=0.668) respectively (p=0.0001) and strongly
      correlated with MVA using PHT post PBMV (r=0.768) (p=0.0001). Post PBMV 14
      patients suffered significant mitral regurgitation 3 of them were transferred to
      surgery. MLS index above 11.75 mm and below 9.15 mm had excellent positive
      predictive value for detecting mild and severe MS respectively. Conclusion: The
      MLS index it is a simple and effective method for assessment of the MVA, it has
      an excellent correlation with MVA with an excellent sensitivity and specificity
      for the prediction of effective MVA. The MLS index cannot evaluate outcome of
      PBMV because it is an anatomical parameter and not flow dependent thus does not
      correlate with grades of mitral regurgitation.

PMID- 30190645
TI  - Assessment of left ventricular regional wall motion abnormalities using regional
      time-volume curves obtained by real time three-dimensional echocardiography.
AB  - Background: Three-dimensional echocardiography provides a volumetric measurement
      of global and regional left ventricular (LV) function. It avoids the subjectivity
      of 2D echocardiography in the assessment of regional wall motion abnormalities
      (RWMA). Purpose: Evaluate the feasibility and practicality of 3D echocardiography
      in the evaluation of ischemic patients with abnormal regional LV contractility.
      Methods: The study included 40 patients with ischemic heart disease and RWMA as
      well as 30 control subjects. They underwent routine clinical examination and
      conventional 2D echocardiographic assessment. Segments were categorized as;
      normal, hypokinetic; akinetic or dyskinetic. Three-dimensional echocardiographic
      images were acquired and later on analyzed offline. Global LV function was semi
      automatically calculated by the machine using volumetric measurements. Regional
      LV function was calculated manually for the 17 LV segments by detecting the end
      diastolic (EDD) and end-systolic (ESD) points on the specific segment volume
      curve and the regional ejection fraction (EF) was calculated by the following
      formula {(EDDx-ESDx)/EDDx}, where x represents the specific segment. Regional EF
      was compared between patients and control subjects. Results: The mean age was
      55.0 +/- 8.0 and 32.6 +/- 8.5 years (P < 0.001) in patients and control groups,
      respectively. No statistically significant difference in EF between 2D and 3D
      images (47.3 +/- 10.5 vs 48.0 +/- 8.0, p = 0.6). There was a good correlation
      between the 2D-RWMA and 3D-regional EF, and this correlation was consistent in
      the whole 17 segments. Conclusion: Three-dimensional echocardiography is an easy,
      non-invasive and objective tool to detect regional wall motion abnormalities in
      ischemic patients. It shows comparable results with conventional 2D images with
      the advantage of quantitative assessment of regional myocardial function.

PMID- 30190647
TI  - Assessment of left ventricular systolic function by tissue Doppler imaging in
      controlled versus uncontrolled type 2 diabetic patients.
AB  - Aim: To detect and quantify early subtle left ventricular (LV) systolic
      dysfunction using Tissue Doppler Imaging in type 2 diabetic patients with
      apparently normal LV ejection fraction. Methods: Ninety age and sex matched
      subjects were enrolled in the study, sixty of them were suffering from type 2
      diabetes mellitus (DM) whom were divided according to HbAlc into 2 groups, 30
      uncontrolled diabetic patients with HbAlc > 8% and 30 controlled diabetic
      patients with HbAlc < 8% and a third group of 30 normal subjects served as
      controls. We excluded patients with inadequate Doppler signal, all structural
      heart diseases, systemic disorders with cardiac involvement and patients with
      false positive HbAlc. Assessment of diastolic function was done by Pulsed Doppler
      through mitral flow and by propagation flow velocity. Assessment of left
      ventricular systolic function was done by conventional echocardiography by 2D
      Simpson method and by Tissue Doppler Imaging (TDI) through detection of mitral
      annular peak systolic velocities. Results: Left ventricular diastolic function
      was compared between the studied groups and showed that the mean peak early
      mitral inflow velocity E wave and the color M-mode flow propagation velocity of
      early diastolic flow (Vp) were significantly lower, and the mean peak late mitral
      inflow velocity A wave was significantly higher in uncontrolled diabetics versus
      controlled diabetic patients and control group with highly significant
      statistical difference (p < 0.001). Assessment of global systolic function by
      conventional Simpson's modified biplane method didn't show significant difference
      between uncontrolled diabetic patients, controlled diabetic patients and normal
      individuals. However, evaluation of systolic function by Tissue Doppler Imaging
      showed that the mean peak longitudinal systolic velocity was significantly
      decreased in uncontrolled diabetic patients when compared to controlled diabetic
      patients and normal individuals, with highly significant statistical difference
      (p < 0.001). A cut-off value for systolic dysfunction detected by TDI in
      uncontrolled diabetic patients was calculated. The peak systolic velocities < 7
      cm/s for medial mitral annulus and < 8.2 cm/s for lateral mitral annulus
      indicated systolic dysfunction in diabetic patients with sensitivity and
      specificity of 96% and 67% respectively for medial mitral annulus while 98% and
      71% respectively for lateral annulus. Conclusion: TDI is a simple and effective
      method for detection of subtle LV systolic dysfunction in type 2 uncontrolled
      diabetic patients.

PMID- 30190648
TI  - Waist height ratio and waist circumference in relation to hypertension,
      Framingham risk score in hospitalized elderly Egyptians.
AB  - Background: Hypertension is a public health problem and obesity is becoming an
      epidemic, increasing the risk of hypertension. Both are risk factors for
      cardiovascular diseases (CVD). Methods: A case control study recruiting 102
      patients aged >=60 years, divided into 55 cases with hypertension and 47 controls
      without. Body mass index (BMI), waist circumference (WC) and waist to height
      ratio (WHtR) were measured as well as lipid profile then Framingham risk score
      (FRS) was calculated. Results: Odds ratio (OR) for hypertension and medium to
      high risk cardiovascular events was the same in female patients using WC and
      WHtR. In male patients, only WHtR increased the risk for hypertension and for
      cardiovascular events, OR significantly increased with higher WHtR compared to
      WC. Conclusion: WHtR and WC are strong risk factors for hypertension and
      cardiovascular events in Egyptian elderly female patients. WHtR is the best
      anthropometric predictor for hypertension and cardiovascular events in male
      patients.

PMID- 30190650
TI  - Contribution of imaging modalities in the diagnosis of middle aortic syndrome.

PMID- 30190651
TI  - Primary cardiac hemangioendothelioma of the mitral valve.
AB  - Primary cardiac hemangioendothelioma is a very rare tumor. Up to now, <20 cases
      have been reported worldwide; involvement of mitral valve by the tumor is
      extremely rare. In this report, a case of hemangioendothelioma arose from the
      mitral valve and was successfully resected, and after few months the tumor
      recurred and infiltrated the heart.

PMID- 30190649
TI  - Role of speckle tracking echocardiography in detecting early left atrial
      dysfunction in hypertensive patients.
AB  - Background: Arterial hypertension adversely affects left atrial (LA) size and
      function, effect on function may precede effect on size. Many techniques were
      used to assess LA function but with pitfalls. Objectives: Early detection of left
      atrial dysfunction with speckle tracking echocardiography in hypertensive
      patients with normal left atrial size. Patients and methods: The study was
      conducted on 50 hypertensive patients and 50 age matched normotensive controls,
      all with normal LA volume index and free from any other cardiovascular disease
      that may affect the LA size or function. They were all subjected to history
      taking, clinical examination and echocardiographic study with assessment of LA
      functions [total LA stroke volume, LA expansion index by conventional 2D
      echocardiography and Global peak atrial longitudinal strain by speckle tracking
      (PALS)], left ventricular (LV) systolic and diastolic functions, and LV mass.
      Results: Different indices of LA dysfunction (Total LA stroke volume, LA
      expansion index and global PALS) were significantly lower in the hypertensive
      group despite the normal LA volume index in all the studied subjects. The
      presence of diabetes mellitus (DM) and higher grade of LV diastolic dysfunction
      were significantly associated with lower global PALS. The higher age, systolic
      blood pressure (BP), body mass index (BMI), LA volume index, and LV mass index
      and the lower LA expansion index were associated with lower global PALS.
      Conclusion: Speckle tracking echocardiography is a useful novel technique in
      detecting LA dysfunction in hypertension even before LA enlargement occurs.

PMID- 30190652
TI  - Multilevel analysis of psychosocial functioning of Adolescents in families
      affected by HIV/AIDS in Benue state, Nigeria.
AB  - Psychosocial functioning is increasing a public health priority issue among young
      people. Previous reports have focused on the effect of personal health conditions
      on the psychosocial well-being of children but contextual analysis of
      environmental or social factors could provide relevant information for
      interventions. In the context of HIV/AIDS, the present study examined the
      personal- and contextual-level predictors of Psychosocial Functioning Index (PFI)
      among adolescents in Benue state, Nigeria. Data on 2,276 adolescents was
      extracted from a cross-sectional study in Benue State for secondary analysis. The
      PFI was obtained using the final score of an existing scale (Adolescents
      Psychosocial Functioning Inventory). Participant's characteristics were
      summarized using descriptive statistics and compared using Chi-square test.
      Multilevel logit models were used to assess the individual- and contextual-level
      predictors of the PFI of adolescents. A nominal p-value <=0.05 was considered
      significant in all analyses. Participants were 14.77+/-2.04 years old and mostly
      female (53.9%). About 19% of the participants have single parents while 62.1%
      have self-employed mothers. Proportion with elevated PFI was significantly higher
      among adolescents who have self-employed mothers (84.4%) and alcohol/substance
      users (82.7%). In adjusted analysis, adolescents who reported alcohol/substance
      use (OR=1.65; 95%CI: 1.14 to 2.38) were twice more likely to have elevated
      psychosocial functioning index compared to non-users. The psychosocial
      functioning index is high among study participants and differs contextually.
      Adolescent's psychosocial functioning depends on their life styles and parents'
      marital and economic situations. Family empowerments and other family level
      intervention programmes will benefit adolescents in these categories.

PMID- 30190653
TI  - Establishment of national diagnostic reference levels (DRLs) for radiotherapy
      localisation computer tomography of the head and neck.
AB  - Aim: The aim of this research is to establish if variation exists in the dose
      delivered for head and neck (HN) localisation computed tomography (CT) imaging in
      radiation therapy (RT); to propose a national diagnostic reference levels (DRLs)
      for this procedure and to make a comparison between the national DRL and a DRL of
      a European sample. Background: CT has become an indispensable tool in
      radiotherapy (RT) treatment planning. It is a requirement of legislation in many
      countries that doses of ionising radiation for medical exposures be kept 'As Low
      As Reasonably Achievable'. There are currently no dose guidelines for RT
      localisation CT of the HN. Materials and methods: All RT departments in Ireland
      and a sample of European departments were surveyed. Dose data on CT dose length
      product (DLP); dose index volume (CTDIvol); current time product; tube voltage
      and scan length was acquired for ten average-sized HN patients from each
      department. DRLs were proposed for DLP and CTDIvol using the rounded 75th
      percentile of the distribution of the means. Results: 42% of Irish departments
      and one European department completed the survey. Significant variation was found
      in the mean DLP, CTDIvol and scan lengths across the Irish departments. The
      proposed Irish DRL is 882 mGy cm and 21 mGy and the European department DRL is
      816 mGy cm and 21 mGy, for DLP and CTDIvol, respectively. Conclusions: Variation
      exists in doses used for HN RT localisation CT. DRLs have been proposed for
      comparison purposes with the aim of dose optimisation.

PMID- 30190654
TI  - Interpersonal Sensitivity as Mediator of the Relations Between War Experiences
      and Mental Illness in War-Affected Youth in Northern Uganda: Findings From the
      WAYS Study.
AB  - The pathways from war experiences to mental health problems are poorly
      understood. The current study aims to assess the role of interpersonal
      sensitivity in the relations between war experiences and mental health problems
      based on data from the War-Affected Youth Survey cohort study. The War-Affected
      Youth Survey is an ongoing research project of formerly abducted children in
      Northern Uganda assessing their war experiences and the risk and protective
      factors in the development of mental health problems. Mediation of the relations
      between war experiences and mental health problems by interpersonal sensitivity
      was analyzed using structural equation modeling. War experiences were related to
      posttraumatic stress disorder through interpersonal sensitivity accounting for
      55% of the variance in their relations, to depression/anxiety through
      interpersonal sensitivity accounting for 89% of the variance in their relations
      (i.e., near complete mediation), and to psychotic symptoms through interpersonal
      sensitivity accounting for 53% of the variance in their relations. The direct
      relation between war experiences, on the one hand, and posttraumatic stress
      disorder and psychotic symptoms, on the other hand, attenuated but remained
      statistically significant. For depression/anxiety, the direct relationship ceased
      to be significant after including interpersonal sensitivity in the model.
      Interpersonal sensitivity is an important determinant of long-term mental health
      problems in war-affected youth. Interventions to improve mental health should
      target youth with high scores on interpersonal sensitivity. Cognitive-behavioral
      therapy to recognize and change cognitive schemas in youth prone to interpersonal
      sensitivity is recommended.

PMID- 30190655
TI  - Safety and Efficacy of Off-label and Unlicensed Medicines in Children.
AB  - Background: The aim of this study was to explore the use of off-label/unlicensed
      drugs to confirm the safety and efficacy of their prescription in children in
      Korea. Methods: In this retrospective study, we analyzed data of patients who
      received any of the 32 drugs between January-December 2014 in tertiary hospitals
      in Korea, including demographics, diagnoses, reasons for the medication,
      administration route, and details of adverse drug reactions. Additionally, the
      mortality in the cohort was assessed. The primary outcomes were efficacy and
      safety, including mortality, of these drugs in pediatric patients. The secondary
      outcomes were the current statuses of the use of off-label/unlicensed drugs in
      two centers. Results: Totally, 5,130 prescriptions were found in 2,779 patients.
      Age (73.5%) and indication (11.7%) were the most frequent reasons for
      prescriptions being off-labeled/unlicensed. Approximately 88% of the
      prescriptions were effective, and 19% of the patients developed adverse drug
      reactions. The number of prescriptions was significantly higher in children with
      adverse drug reactions than it was in those without (2.8 vs. 1.5; P < 0.001). The
      number of prescribed off-label/unlicensed medicines and age at prescription were
      independently associated with adverse drug events (odds ratio, 1.55 and 1.1; P <
      0.001 and 0.034, respectively). Conclusion: Children are still prescribed
      medicines that are not authorized in terms of age, weight, indications, or routes
      of administration. Therefore, many old products require re-assessment of
      authorization. More prospective clinical studies should be performed to confirm
      the efficacy and safety of drugs in the pediatric population.

PMID- 30190656
TI  - Therapeutic Effects of Leuprorelin (Leuprolide Acetate) in Sexual Offenders with
      Paraphilia.
AB  - Background: This study examined the clinical effects of leuprolide acetate in
      sexual offenders with paraphilic disorders evaluated by means of objective
      psychiatric assessment. Methods: The subjects of this study were seven sexual
      offenders who were being treated by means of an injection for sexual impulse
      control by a court order. They had been diagnosed with paraphilia by a
      psychiatrist based on the Diagnostic and Statistical Manual of Mental Disorders,
      5th edition (DSM-5) and had been put on probation by the Ministry of Justice
      between January 2016 and December 2016. Results: After twelve months, we observed
      significant improvement in symptoms, as decrease of abnormal sexual interest and
      activity, sexual fantasy, Clinical Global Impression-Severity (CGI-S), and
      Clinical Global Impression-Impulsivity (GCI-I). There were a mild feminization of
      the body shape, feelings of fatigue, and mild hot flushes. No other adverse
      effect was reported. Conclusion: These results suggested that the clinical
      effects of leuprolide acetate in sexual offenders might be an effective treatment
      and safety strategy.

PMID- 30190657
TI  - Prognostic Factors of Penile Cancer and the Efficacy of Adjuvant Treatment after
      Penectomy: Results from a Multi-institution Study.
AB  - Background: Penile cancer is a rare malignancy associated with high rates of
      mortality and morbidity. Currently, the efficacy of adjuvant treatment (AT),
      including radiotherapy and chemotherapy, for penile cancer remains unclear.
      Therefore, we investigated the prognostic factors for treatment outcomes and the
      efficacy of AT in consecutive patients who underwent penectomy for penile cancer
      at multiple Korean institutions between 1999 and 2013. Methods: AT was defined as
      the administration of chemotherapy, radiotherapy, or both within 12 months after
      initial treatment. All patients were divided into two groups according to the AT
      status. Results: Forty-three patients (median age 67.0 years) with a median
      follow-up after penectomy of 26.4 (interquartile range: 12.0-62.8) months were
      enrolled. Patients with AT had a significantly higher pathologic stage. However,
      no differences in age, histologic grade, or type of surgery were identified
      according to the presence of AT. The 3- and 5-year cancer-specific survival (CSS)
      rates were 79.0% and 33.0%, respectively. In a multivariate analysis, American
      Joint Committee on Cancer (AJCC) stage >= III disease was an independent
      predictor of CSS and recurrence-free survival (RFS). However, AT was not
      associated with CSS and RFS. The type of primary surgical treatment and inguinal
      lymph node dissection at diagnosis were also not significantly associated with
      overall survival, CSS, or RFS. Conclusion: AJCC stage >= III disease, which
      mainly reflects lymph node positivity, is a significant prognosticator in
      patients with penile cancer. By contrast, AT does not seem to affect CSS and RFS.

PMID- 30190658
TI  - Premature Deaths Attributable to Exposure to Ambient Fine Particulate Matter in
      the Republic of Korea: Implication for Future Environmental Health.

PMID- 30190659
TI  - Premature Deaths Attributable to Long-term Exposure to Ambient Fine Particulate
      Matter in the Republic of Korea.
AB  - Background: Ambient fine particulate matter (PM2.5) is the major environmental
      health risk factor in Korea. Exposure to PM2.5 has been a growing public concern
      nationwide. With the rapid aging of the Korean population, the health effects
      attributable to long-term exposure to PM2.5 were expected to increase further in
      the future. We aimed to estimate premature deaths attributable to long-term
      exposure to ambient PM2.5 in Korea. Methods: A modelled estimation of long-term
      exposure to PM2.5 was used to calculate the nationwide exposure level. Hazard
      ratios of long-term exposure to PM2.5 were obtained from a large prospective
      cohort study in North America. Modified cause of death (CoD) data, which applied
      the garbage code reclassification algorithm, were used to calculate premature
      deaths attributable to long-term exposure to PM2.5. Results: From 1990 to 2013,
      the average population-weighted PM2.5 concentration in Korea was 30.2 MUg/m3. The
      estimated number of premature deaths was 17,203 (95% confidence interval [CI],
      11,056-22,772). The most common CoD was ischemic stroke (5,382; 3,101-7,403),
      followed by cancer of trachea, bronchus, and lung (4,958; 2,857-6,820),
      hemorrhagic stroke (3,452; 1,989-4,748), and ischemic heart disease (3,432; 1,383
      5,358). Conclusion: Premature deaths due to long-term exposure to PM2.5 accounted
      for 6.4% of all deaths in Korea. However, individual efforts alone cannot prevent
      the effects of air pollution. This disease burden study can serve as a basis for
      the establishment of government policies and budgets and can be used to assess
      the effectiveness of environmental health policies.

PMID- 30190660
TI  - Towards understanding aromatase inhibitory activity via QSAR modeling.
AB  - Aromatase is a rate-limiting enzyme for estrogen biosynthesis that is
      overproduced in breast cancer tissue. To block the growth of breast tumors,
      aromatase inhibitors (AIs) are employed to bind and inhibit aromatase in order to
      lower the amount of estrogen produced in the body. Although a number of synthetic
      aromatase inhibitors have been released for clinical use in the treatment of
      hormone-receptor positive breast cancer, these inhibitors may lead to undesirable
      side effects (e.g. increased rash, diarrhea and vomiting; effects on the bone,
      brain and heart) and therefore, the search for novel AIs continues. Over the past
      decades, there has been an intense effort in employing medicinal chemistry and
      quantitative structure-activity relationship (QSAR) to shed light on the
      mechanistic basis of aromatase inhibition. To the best of our knowledge, this
      article constitutes the first comprehensive review of all QSAR studies of both
      steroidal and non-steroidal AIs that have been published in the field. Herein, we
      summarize the experimental setup of these studies as well as summarizing the key
      features that are pertinent for robust aromatase inhibition.

PMID- 30190662
TI  - Highlight report: Diploptera functata (cockroach) milk as next superfood.

PMID- 30190661
TI  - Is autophagy associated with diabetes mellitus and its complications? A review.
AB  - Diabetes mellitus (DM) is an endocrine disorder. In coming decades it will be one
      of the leading causes of death globally. The key factors in the pathogenesis of
      diabetes are cellular injuries and disorders of energy metabolism leading to
      severe diabetic complications. Recent studies have confirmed that autophagy plays
      a pivotal role in diabetes and its complications. It has been observed that
      autophagy regulates the normal function of pancreatic beta cells and insulin
      target tissues, such as skeletal muscle, liver, and adipose tissue. This review
      will summarize the regulation of autophagy in diabetes and its complications, and
      explore how this process would emerge as a potential therapeutic target for
      diabetes treatment.

PMID- 30190663
TI  - Prevalence of self-reported work-related illness and injuries among building
      construction workers, Shiraz, Iran.
AB  - The construction industry is one of the largest and most hazardous industries in
      the world, which has a direct role in the development of countries. The purpose
      of this study was to investigate the prevalence of self-reported work-related
      illness and injuries among construction workers in Shiraz, Iran. 850 randomly
      selected workers from 2450 construction sites completed a self-statement
      questionnaire regarding the prevalence of self-reported work-related illness and
      injuries (WRIIs), in Shiraz, Iran. The association of WRII with demographic
      variables were studied. The overall prevalence rate of occupational injuries was
      31 %. Musculoskeletal disorders (53.3 %), eye diseases (34.1 %) and skin diseases
      (30.1 %) have been the most prevalent work-related illnesses among construction
      workers, respectively. The prevalence of WRIIs among construction workers was
      significantly associated with age, education, marriage, work experience, safety
      training programs and number of workers in the workplace as well as employment
      status. Considering the high prevalence of WRIIs among construction workers, more
      stringent occupational safety and health interventions are recommended in
      construction workplaces.

PMID- 30190665
TI  - 18 beta-glycyrrhetinic acid ameliorates the cognitive functions and decreases the
      recurrence rate of pituitary adenomas patients.
AB  - Pituitary adenomas, the most common tumors of all intracranial neoplasms, may
      cause either symptoms of mass effect or symptoms of hormone abnormal production.
      Besides physical damages, patients with pituitary adenomas always suffer from
      cognitive impairments, mainly in memory and executive functions. 18 beta
      glycyrrhetinic acid (GA) has been found to exhibit anti-tumor effects in rat
      pituitary adenoma-derived cells. The aim of this paper was to investigate the
      effect of GA in postoperative clinical application. In this study, we recruited
      647 patients with pituitary adenoma and 135 patients who dropped out were
      excluded from analysis. Thus, altogether 512 patients with pituitary adenoma
      completed the study, of whom 268 were treated with GA, and 244 were treated with
      placebo. Cognitive assessments, eyesight, tumor size, and hormone secretion
      levels were examined before and after surgery in both groups. All patients
      underwent surgeries by single-nostril transsphenoidal approach for their first
      time medical treatment. Hormone secretion levels were measured by blood samples
      and Magnetic resonance imaging (MRI) was used for examining the status of tumor
      excision. Compared with placebo group, the scores in orientation, language
      (expression), memory (recall), practice, abstract thinking, and MiniMental State
      Examination (MMSE) were significantly improved (p < 0.05) in GA treated group
      after one month of surgery. After six months, there was still a significant
      increase in abstract thinking scores. Moreover, GA did not impact the overall
      survival percentage of patients enrolled during our five-year follow-up, but
      significantly reduced the recurrence rate than that of the placebo group. GA
      significantly improved the cognitive functions at the early stage after surgery
      and had a long-termed efficacy on abstract thinking. Notably, GA inhibited the
      five-year recurrence rate of the recruited pituitary adenomas patients.

PMID- 30190666
TI  - The cardiac niche role in cardiomyocyte differentiation of rat bone marrow
      derived stromal cells: comparison between static and microfluidic cell culture
      methods.
AB  - Due to the restricted potential of the heart to regenerate its damaged region,
      stem cell therapy is a promising treatment modality for myocardial infarction. It
      has been shown that incubation of bone marrow-derived stromal cells (BMSCs) with
      initial steps of cardiac differentiation in vitro, can have a significant effect
      on their therapeutic potential to treat myocardial infarction. Based on these
      well-established principals we were encouraged to study the direct co-culture of
      rat BMSCs with neonatal mouse almost pure cardiomyocytes (APCs) and cardiac niche
      cells (CNCs) in static 2D and microfluidic cell culture systems. Our results
      showed that the difference regarding the beating rate in isolated APCs and CNCs
      in both 2D and the microfluidic system was not statistically significant for 30
      days. No beat rate could be observed in induced BMSCs in all groups during
      experiment time. Except for BMSCs cultured alone in both experimental culture
      conditions, data obtained from Real-time PCR analysis showed that differentiated
      BMSCs in all co-cultured groups expressed GATA4, Nkx2.5, CX43, cTnI, cTnT, and
      beta-MHC during 4 weeks. BMSCs demonstrated a higher expression of these cardiac
      factors in microfluidic chips than those co-cultured in 24 well plates. Moreover,
      immunocytochemistry (ICC), also revealed the GATA4 expression in differentiated
      BMSCs in all co-cultured groups. It was found that, when combined with shear
      stress, co-culture with cardiomyocyte can differentiate BMSCs significantly
      toward cardiomyocyte rather than co-culture alone.

PMID- 30190664
TI  - Unraveling the bioactivity of anticancer peptides as deduced from machine
      learning.
AB  - Cancer imposes a global health burden as it represents one of the leading causes
      of morbidity and mortality while also giving rise to significant economic burden
      owing to the associated expenditures for its monitoring and treatment. In spite
      of advancements in cancer therapy, the low success rate and recurrence of tumor
      has necessitated the ongoing search for new therapeutic agents. Aside from drugs
      based on small molecules and protein-based biopharmaceuticals, there has been an
      intense effort geared towards the development of peptide-based therapeutics owing
      to its favorable and intrinsic properties of being relatively small, highly
      selective, potent, safe and low in production costs. In spite of these
      advantages, there are several inherent weaknesses that are in need of attention
      in the design and development of therapeutic peptides. An abundance of data on
      bioactive and therapeutic peptides have been accumulated over the years and the
      burgeoning area of artificial intelligence has set the stage for the lucrative
      utilization of machine learning to make sense of these large and high-dimensional
      data. This review summarizes the current state-of-the-art on the application of
      machine learning for studying the bioactivity of anticancer peptides along with
      future outlook of the field. Data and R codes used in the analysis herein are
      available on GitHub at https://github.com/Shoombuatong2527/anticancer-peptides
      review.

PMID- 30190667
TI  - Anti-inflammation effects of 8-oxo-9-octadecenoic acid isolated from Undaria
      peterseniana in lipopolysaccharide-stimulated macrophage cells.
AB  - The aim of this study was to investigate the anti-inflammatory activity of 8-oxo
      9-octadecenoic acid (OOA) isolated from Undaria peterseniana by examining its
      ability to inhibit the lipopolysaccharide (LPS)-induced production of
      inflammatory mediators in RAW 264.7 macrophage cells. We found that OOA
      significantly suppressed the LPS-induced production of nitric oxide (NO) and
      inflammatory cytokines. OOA downregulated the LPS-induced expression of inducible
      nitric oxide synthase and cyclooxygenase-2 proteins. With respect to
      proinflammatory signaling pathways, OOA inhibited LPS-induced mitogen-activated
      protein kinase signaling by inhibiting the phosphorylation of c-Jun N-terminal
      kinase (JNK) and extracellular signal-regulated kinase (ERK). Moreover, OOA
      inhibited LPS-induced nuclear factor (NF)-kappaB signaling by reducing the
      phosphorylation of IkappaB-alpha and p50 proteins. These results indicate that
      OOA significantly reduces proinflammatory signaling, which results in reduced
      expression of cytokines and proinflammatory mediators. Taken together, these
      results suggest that OOA has potent anti-inflammatory effects and could be
      considered an effective anti-inflammatory agent.

PMID- 30190668
TI  - Derivation of indoor air guidance values for volatile organic compounds (VOC)
      emitted from polyurethane flexible foam: VOC with repeated dose toxicity data.
AB  - Polyurethane Flexible Foams (PUF) are versatile materials used in upholstered
      furniture and bed mattresses. Due to the production procedure, fresh foams emit
      volatile organic compounds (VOC). Chamber tests issued by the European
      association of flexible polyurethane foam blocks manufacturers (EUROPUR) revealed
      certain levels of VOCs, and the emission rates are declining over time. To assess
      the risk associated to these VOCs which, as a consequence, might be detectable in
      indoor air where these PUF are used. To evaluate the risk for consumers, their
      concentration can be matched against existing benchmarks for indoor air. These
      benchmarks are, for example, guidance values derived by the Advisory Group for
      Indoor Air Guidance Values of the German UBA (RW-values), Lowest Concentrations
      of Interest (LCI) for building products, or against derived no effect levels
      (DNELs) for consumers, defined in registration dossiers under the European
      Regulation No. 1907/2006. In this paper, indoor air guidance values are derived
      for some VOCs which do have neither RW- nor LCI-values, and no DNELs for
      consumers. Substances covered are trimethylsilanol, fluorotrimethylsilane,
      chloropropanol, propanal, triethylenediamine and 2,2,3,3-tetramethyl
      succinodinitrile.

PMID- 30190669
TI  - Red and processed meat and risk of colorectal cancer: an update.

PMID- 30190670
TI  - SpiLinC: Spiking Liquid-Ensemble Computing for Unsupervised Speech and Image
      Recognition.
AB  - In this work, we propose a Spiking Neural Network (SNN) consisting of input
      neurons sparsely connected by plastic synapses to a randomly interlinked liquid,
      referred to as Liquid-SNN, for unsupervised speech and image recognition. We
      adapt the strength of the synapses interconnecting the input and liquid using
      Spike Timing Dependent Plasticity (STDP), which enables the neurons to self-learn
      a general representation of unique classes of input patterns. The presented
      unsupervised learning methodology makes it possible to infer the class of a test
      input directly using the liquid neuronal spiking activity. This is in contrast to
      standard Liquid State Machines (LSMs) that have fixed synaptic connections
      between the input and liquid followed by a readout layer (trained in a supervised
      manner) to extract the liquid states and infer the class of the input patterns.
      Moreover, the utility of LSMs has primarily been demonstrated for speech
      recognition. We find that training such LSMs is challenging for complex pattern
      recognition tasks because of the information loss incurred by using fixed input
      to liquid synaptic connections. We show that our Liquid-SNN is capable of
      efficiently recognizing both speech and image patterns by learning the rich
      temporal information contained in the respective input patterns. However, the
      need to enlarge the liquid for improving the accuracy introduces scalability
      challenges and training inefficiencies. We propose SpiLinC that is composed of an
      ensemble of multiple liquids operating in parallel. We use a "divide and learn"
      strategy for SpiLinC, where each liquid is trained on a unique segment of the
      input patterns that causes the neurons to self-learn distinctive input features.
      SpiLinC effectively recognizes a test pattern by combining the spiking activity
      of the constituent liquids, each of which identifies characteristic input
      features. As a result, SpiLinC offers competitive classification accuracy
      compared to the Liquid-SNN with added sparsity in synaptic connectivity and
      faster training convergence, both of which lead to improved energy efficiency in
      neuromorphic hardware implementations. We validate the efficacy of the proposed
      Liquid-SNN and SpiLinC on the entire digit subset of the TI46 speech corpus and
      handwritten digits from the MNIST dataset.

PMID- 30190671
TI  - From Neural Crest Development to Cancer and Vice Versa: How p75NTR and
      (Pro)neurotrophins Could Act on Cell Migration and Invasion?
AB  - The p75 neurotrophin receptor (p75NTR), also known as low-affinity nerve growth
      factor, belongs to the tumor necrosis factor family of receptors. p75NTR is
      widely expressed in the nervous system during the development, as well as, in the
      neural crest population, since p75NTR has been described as ubiquitously
      expressed and considered as a neural crest marker. Neural crest cells (NCCs)
      constitute an transient population accurately migrating and invading, with
      precision, defined sites of the embryo. During migration, NCCs are guided along
      distinct migratory pathways by specialized molecules present in the extracellular
      matrix or on the surfaces of those cells. Two main processes direct NCC migration
      during the development: (1) an epithelial-to-mesenchymal transition and (2) a
      process known as contact inhibition of locomotion. In adults, p75NTR remains
      expressed by NCCs and has been identified in an increasing number of cancer
      cells. Nonetheless, the regulation of the expression of p75NTR and the underlying
      mechanisms in stem cell biology or cancer cells have not yet been sufficiently
      addressed. The main objective of this review is therefore to analyze elements of
      our actual knowledge regarding p75NTR roles during the development (mainly
      focusing on neural crest development) and see how we can transpose that
      information from development to cancer (and vice versa) to better understand the
      link between p75NTR and cell migration and invasion. In this review, we
      successively analyzed the molecular mechanisms of p75NTR when it interacts with
      several coreceptors and/or effectors. We then analyzed which signaling pathways
      are the most activated or linked to NCC migration during the development.
      Regarding cancer, we analyzed the described molecular pathways underlying cancer
      cell migration when p75NTR was correlated to cancer cell migration and invasion.
      From those diverse sources of information, we finally summarized potential
      molecular mechanisms underlying p75NTR activation in cell migration and invasion
      that could lead to new research areas to develop new therapeutic protocols.

PMID- 30190673
TI  - 3D Hippocampal Place Field Dynamics in Free-Flying Echolocating Bats.
AB  - A large body of laboratory research has investigated the process by which
      environmental cues are acquired and used for spatial navigation in rodents;
      however, the key to differentiating between species specializations and general
      principles lies in comparative research. Rodent research has focused on a class
      of neurons in the hippocampus implicated in the representation of allocentric
      space - termed place cells - and the process by which these representations form.
      One class of models of hippocampal place field formation depends on continuous
      theta, a low frequency brain oscillation that is prevalent in crawling rodents.
      Comparative studies of hippocampal activity in echolocating bats have reported
      many findings that parallel the rodent literature, but also describe noteworthy
      species differences, especially with respect to theta rhythm. Here, we first
      discuss studies of the bat hippocampal formation and point to gaps in our
      knowledge, which motivate our new lines of inquiry. We present data from the free
      flying laryngeal echolocating big brown bat, which shows 3-D place cells without
      continuous theta, similar to reports from the lingual echolocating Egyptian fruit
      bat. We also report findings, which demonstrate that the animal's control over
      echolocation call rate (sensory sampling) influences place field tuning. These
      results motivate future comparative research on hippocampal function in the
      context of natural sensory-guided behaviors.

PMID- 30190672
TI  - gamma2 GABAAR Trafficking and the Consequences of Human Genetic Variation.
AB  - GABA type A receptors (GABAARs) mediate the majority of fast inhibitory
      neurotransmission in the central nervous system (CNS). Most prevalent as
      heteropentamers composed of two alpha, two beta, and a gamma2 subunit, these
      ligand-gated ionotropic chloride channels are capable of extensive genetic
      diversity (alpha1-6, beta1-3, gamma1-3, delta, ??, ??, pi, rho1-3). Part of this
      selective GABAAR assembly arises from the critical role for gamma2 in maintaining
      synaptic receptor localization and function. Accordingly, mutations in this
      subunit account for over half of the known epilepsy-associated genetic anomalies
      identified in GABAARs. Fundamental structure-function studies and cellular
      pathology investigations have revealed dynamic GABAAR trafficking and synaptic
      scaffolding as critical regulators of GABAergic inhibition. Here, we introduce in
      vitro and in vivo findings regarding the specific role of the gamma2 subunit in
      receptor trafficking. We then examine gamma2 subunit human genetic variation and
      assess disease related phenotypes and the potential role of altered GABAAR
      trafficking. Finally, we discuss new-age imaging techniques and their potential
      to provide novel insight into critical regulatory mechanisms of GABAAR function.

PMID- 30190675
TI  - Topical Application of Adelmidrol + Trans-Traumatic Acid Enhances Skin Wound
      Healing in a Streptozotocin-Induced Diabetic Mouse Model.
AB  - Impaired wound healing is considered to be one of the severe complications
      associated with diabetes. Adelmidrol and trans-traumatic acid are commonly called
      Nevamast(r). This gel consists precisely of 2% adelmidrol and 1% trans-traumatic
      acid. Thanks to its components, it is capable of favoring the natural process of
      skin re-epithelialization. This study tests the theory that topical usage of
      adelmidrol + trans-traumatic acid has important effects on the healing and
      closure of diabetic wounds in a streptozotocin (STZ)-induced diabetic mouse
      model. Diabetes was induced by intraperitoneal injection of STZ (60 mg/kg) in
      0.01 M citrate buffer (pH 4.5) administrated for 5 consecutive days. After
      diabetes induction, two longitudinal incisions were made on the dorsum of the
      mice. The animals were killed between 6 and 12 days from wound induction. We
      found that diabetic mice compared to control mice presented: a retarded wound
      closure, characterized by an important reduction in the levels of transforming
      growth factor-beta, plus an important increase of vascular endothelial growth
      factor and endothelial-type nitric oxide synthase expression, together with a
      reduction of adhesion molecules such as intercellular adhesion molecule-1 and P
      selectin and a prolonged elevation of the levels of matrix metalloproteinase-9
      and matrix metalloproteinase-2 in wound tissues. This study demonstrates that
      topical application of adelmidrol + trans-traumatic acid has important effects on
      the healing and closure of diabetic wounds in an STZ-induced diabetic mouse
      model.

PMID- 30190674
TI  - A Comprehensive Review of Magnetoencephalography (MEG) Studies for Brain
      Functionality in Healthy Aging and Alzheimer's Disease (AD).
AB  - Neural oscillations were established with their association with
      neurophysiological activities and the altered rhythmic patterns are believed to
      be linked directly to the progression of cognitive decline.
      Magnetoencephalography (MEG) is a non-invasive technique to record such neuronal
      activity due to excellent temporal and fair amount of spatial resolution. Single
      channel, connectivity as well as brain network analysis using MEG data in resting
      state and task-based experiments were analyzed from existing literature. Single
      channel analysis studies reported a less complex, more regular and predictable
      oscillations in Alzheimer's disease (AD) primarily in the left parietal, temporal
      and occipital regions. Investigations on both functional connectivity (FC) and
      effective (EC) connectivity analysis demonstrated a loss of connectivity in AD
      compared to healthy control (HC) subjects found in higher frequency bands. It has
      been reported from multiplex network of MEG study in AD in the affected regions
      of hippocampus, posterior default mode network (DMN) and occipital areas,
      however, conclusions cannot be drawn due to limited availability of clinical
      literature. Potential utilization of high spatial resolution in MEG likely to
      provide information related to in-depth brain functioning and underlying factors
      responsible for changes in neuronal waves in AD. This review is a comprehensive
      report to investigate diagnostic biomarkers for AD may be identified by from MEG
      data. It is also important to note that MEG data can also be utilized for the
      same pursuit in combination with other imaging modalities.

PMID- 30190676
TI  - Biological Activity of Flavonoids and Rare Sesquiterpene Lactones Isolated From
      Centaurea ragusina L.
AB  - The endemic Croatian species Centaurea ragusina L., like other species from the
      genus Centaurea, has been traditionally used in Croatia as an antibacterial agent
      and for the treatment of gastrointestinal and urogenital disorders. In several
      chromatographic steps, three flavonoids and three sesquiterpene lactones (STLs)
      were isolated and identified from the most active fractions of the ethanol
      extract. Two STLs, one for which we created the trivial name ragusinin, and
      hemistepsin A are here reported for the first time as constituents of the genus
      Centaurea. All six compounds were screened for their effect on several tumor and
      one normal cell lines. Among them, ragusinin showed the best bioactivity and high
      specificity to affect tumor murine SCCVII, human HeLa and Caco-2 cell lines, but
      not the viability of normal V79 fibroblasts. Due to these characteristics the
      action of ragusinin was investigated in more detail. Since DNA is the primary
      target for many drugs with antibacterial and anticancer activity, we studied its
      interaction with ragusinin. Rather moderate binding affinity to DNA excluded it
      as the primary target of ragusinin. Due to the possibility of STL interaction
      with glutathione (GSH), the ubiquitous peptide that traps reactive compounds and
      other xenobiotics to prevent damage to vital proteins and nucleic acids, its role
      in deactivation of ragusinin was evaluated. Addition of the GSH precursor N
      acetyl-cysteine potentiated the viability of HeLa cells, while the addition of
      GSH inhibitor L-buthionine sulfoximine decreased it. Moreover, pre-treatment of
      HeLa cells with the inhibitor of glutathione-S-transferase decreased their
      viability indicating the detoxifying role of GSH in ragusinin treated cells. Cell
      death, derived by an accumulation of cells in a G2 phase of the cell cylce, was
      shown to be independent of poly (ADP-ribose) polymerase and caspase-3 cleavage
      pointing toward an alternative cell death pathway.

PMID- 30190677
TI  - Morphological Substrates for Atrial Arrhythmogenesis in a Heart With
      Atrioventricular Septal Defect.
AB  - Due to advances in corrective surgery, congenital heart disease has an ever
      growing patient population. Atrial arrhythmias are frequently observed pre- and
      post-surgical correction. Pharmaceutical antiarrhythmic therapy is not always
      effective, therefore many symptomatic patients undergo catheter ablation therapy.
      In patients with atrioventricular septal defects (AVSD), ablation therapy itself
      has mixed success; arrhythmogenic recurrences are common, and because of the
      anatomical displacement of the atrioventricular node, 3-degree heart block post
      ablation is a real concern. In order to develop optimal and safe ablation
      strategies, the field of congenital cardiac electrophysiology must combine
      knowledge from clinical electrophysiology with a thorough understanding of the
      anatomical substrates for arrhythmias. Using image-based analysis and multi
      cellular mathematical modeling of electrical activation, we show how the
      anatomical alterations characteristic of an AVSD serve as arrhythmogenic
      substrates. Using ex-vivo contrast enhanced micro-computed tomography we imaged
      post-mortem the heart of a 5 month old male with AVSD at an isometric spatial
      resolution of 38 MUm. Morphological analysis revealed the 3D disposition of the
      cardiac conduction system for the first time in an intact heart with this human
      congenital malformation. We observed displacement of the compact atrioventricular
      node inferiorly to the ostium of the coronary sinus. Myocyte orientation analysis
      revealed that the normal arrangement of the major atrial muscle bundles was
      preserved but was modified in the septal region. Models of electrical activation
      suggest the disposition of the myocytes within the atrial muscle bundles
      associated with the "fast pathway," together with the displaced atrioventricular
      node, serve as potential substrates for re-entry and possibly atrial
      fibrillation. This study used archived human hearts, showing them to be a
      valuable resource for the mathematical modeling community, and opening new
      possibilities for the investigations of arrhythmogenesis and ablation strategies
      in the congenitally malformed heart.

PMID- 30190679
TI  - Systematic Analysis of Mouse Genome Reveals Distinct Evolutionary and Functional
      Properties Among Circadian and Ultradian Genes.
AB  - In living organisms, biological clocks regulate 24 h (circadian) molecular,
      physiological, and behavioral rhythms to maintain homeostasis and synchrony with
      predictable environmental changes, in particular with those induced by Earth's
      rotation on its axis. Harmonics of these circadian rhythms having periods of 8
      and 12 h (ultradian) have been documented in several species. In mouse liver,
      harmonics of the 24-h period of gene transcription hallmarked genes oscillating
      with a frequency two or three times faster than circadian periodicity. Many of
      these harmonic transcripts enriched pathways regulating responses to
      environmental stress and coinciding preferentially with subjective dawn and dusk.
      At this time, the evolutionary history of genes with rhythmic expression is still
      poorly known and the role of length-of-day changes due to Earth's rotation speed
      decrease over the last four billion years is totally ignored. We hypothesized
      that ultradian and stress anticipatory genes would be more evolutionarily
      conserved than circadian genes and background non-oscillating genes. To
      investigate this issue, we performed broad computational analyses of
      genes/proteins oscillating at different frequency ranges across several species
      and showed that ultradian genes/proteins, especially those oscillating with a 12
      h periodicity, are more likely to be of ancient origin and essential in mice. In
      summary, our results show that genes with ultradian transcriptional patterns are
      more likely to be phylogenetically conserved and associated with the primeval and
      inevitable dawn/dusk transitions.

PMID- 30190682
TI  - NFAT5 Isoform C Controls Biomechanical Stress Responses of Vascular Smooth Muscle
      Cells.
AB  - Vascular cells are continuously exposed to mechanical stress that may wreak havoc
      if exceeding physiological levels. Consequently, mechanisms facing such a
      challenge are indispensable and contribute to the adaptation of the cellular
      phenotype. To this end, vascular smooth muscle cells (VSMCs) activate
      mechanoresponsive transcription factors promoting their proliferation and
      migration to initiate remodeling the arterial wall. In mechanostimulated VSMCs,
      we identified nuclear factor of activated T-cells 5 (NFAT5) as transcriptional
      regulator protein and intended to unravel mechanisms controlling its expression
      and nuclear translocation. In cultured human VSMCs, blocking RNA synthesis
      diminished both baseline and stretch-induced NFAT5 mRNA expression while
      inhibition of the proteasome promoted accumulation of the NFAT5 protein. Detailed
      PCR analyses indicated a decrease in expression of NFAT5 isoform A and an
      increase in isoform C in mechanoactivated VSMCs. Upon overexpression, only NFAT5c
      was capable to enter the nucleus in control- and stretch-stimulated VSMCs. As
      evidenced by analyses of NFAT5c mutants, nuclear translocation required
      palmitoylation, phosphorylation at Y143 and was inhibited by phosphorylation at
      S1197. On the functional level, overexpression of NFAT5c forces its accumulation
      in the nucleus as well as transcriptional activity and stimulated VSMC
      proliferation and migration. These findings suggest that NFAT5 is continuously
      expressed and degraded in resting VSMCs while expression and accumulation of
      isoform C in the nucleus is facilitated during biomechanical stress to promote an
      activated VSMC phenotype.

PMID- 30190681
TI  - Outdoor Temperature Influences Cold Induced Thermogenesis in Humans.
AB  - Objective: Energy expenditure (EE) increases in response to cold exposure, which
      is called cold induced thermogenesis (CIT). Brown adipose tissue (BAT) has been
      shown to contribute significantly to CIT in human adults. BAT activity and CIT
      are acutely influenced by ambient temperature. In the present study, we
      investigated the long-term effect of seasonal temperature variation on human CIT.
      Materials and Methods: We measured CIT in 56 healthy volunteers by indirect
      calorimetry. CIT was determined as difference between EE during warm conditions
      (EEwarm) and after a defined cold stimulus (EEcold). We recorded skin
      temperatures at eleven anatomically predefined locations, including the
      supraclavicular region, which is adjacent to the main human BAT depot. We
      analyzed the relation of EE, CIT and skin temperatures to the daily minimum,
      maximum and mean outdoor temperature averaged over 7 or 30 days, respectively,
      prior to the corresponding study visit by linear regression. Results: We observed
      a significant inverse correlation between outdoor temperatures and EEcold and
      CIT, respectively, while EEwarm was not influenced. The daily maximum temperature
      averaged over 7 days correlated best with EEcold (R2 = 0.123, p = 0.008) and CIT
      (R2 = 0.200, p = 0.0005). The mean skin temperatures before and after cold
      exposure were not related to outdoor temperatures. However, the difference
      between supraclavicular and parasternal skin temperature after cold exposure was
      inversely related to the average maximum temperature during the preceding 7 days
      (R2 = 0.07575, p = 0.0221). Conclusion: CIT is significantly related to outdoor
      temperatures indicating dynamic adaption of thermogenesis and BAT activity to
      environmental stimuli in adult humans. Clinical Trial Registration:
      www.ClinicalTrials.gov, Identifier NCT02682706.

PMID- 30190680
TI  - Intravenous Vitamin C for Cancer Therapy - Identifying the Current Gaps in Our
      Knowledge.
AB  - The use of intravenous vitamin C (IVC) for cancer therapy has long been an area
      of intense controversy. Despite this, high dose IVC has been administered for
      decades by complementary health care practitioners and physicians, with little
      evidence base resulting in inconsistent clinical practice. In this review we pose
      a series of questions of relevance to both researchers and clinicians, and also
      patients themselves, in order to identify current gaps in our knowledge. These
      questions include: Do oncology patients have compromised vitamin C status? Is
      intravenous the optimal route of vitamin C administration? Is IVC safe? Does IVC
      interfere with chemotherapy or radiotherapy? Does IVC decrease the toxic side
      effects of chemotherapy and improve quality of life? What are the relevant
      mechanisms of action of IVC? What are the optimal doses, frequency, and duration
      of IVC therapy? Researchers have made massive strides over the last 20 years and
      have addressed many of these important aspects, such as the best route for
      administration, safety, interactions with chemotherapy, quality of life, and
      potential mechanisms of action. However, we still do not know the answers to a
      number of fundamental questions around best clinical practice, such as how much,
      how often and for how long to administer IVC to oncology patients. These
      questions point the way forward for both basic research and future clinical
      trials.

PMID- 30190684
TI  - Ca2+ Cycling Impairment in Heart Failure Is Exacerbated by Fibrosis: Insights
      Gained From Mechanistic Simulations.
AB  - Heart failure (HF) is characterized by altered Ca2+ cycling, resulting in cardiac
      contractile dysfunction. Failing myocytes undergo electrophysiological
      remodeling, which is known to be the main cause of abnormal Ca2+ homeostasis.
      However, structural remodeling, specifically proliferating fibroblasts coupled to
      myocytes in the failing heart, could also contribute to Ca2+ cycling impairment.
      The goal of the present study was to systematically analyze the mechanisms by
      which myocyte-fibroblast coupling could affect Ca2+ dynamics in normal conditions
      and in HF. Simulations of healthy and failing human myocytes were performed using
      established mathematical models, and cells were either isolated or coupled to
      fibroblasts. Univariate and multivariate sensitivity analyses were performed to
      quantify effects of ion transport pathways on biomarkers computed from
      intracellular [Ca2+] waveforms. Variability in ion channels and pumps was imposed
      and populations of models were analyzed to determine effects on Ca2+ dynamics.
      Our results suggest that both univariate and multivariate sensitivity analyses
      are valuable methodologies to shed light into the ionic mechanisms underlying
      Ca2+ impairment in HF, although differences between the two methodologies are
      observed at high parameter variability. These can result from either the fact
      that multivariate analyses take into account ion channels or non-linear effects
      of ion transport pathways on Ca2+ dynamics. Coupling either healthy or failing
      myocytes to fibroblasts decreased Ca2+ transients due to an indirect sink effect
      on action potential (AP) and thus on Ca2+ related currents. Simulations that
      investigated restoration of normal physiology in failing myocytes showed that
      Ca2+ cycling can be normalized by increasing SERCA and L-type Ca2+ current
      activity while decreasing Na+-Ca2+ exchange and SR Ca2+ leak. Changes required to
      normalize APs in failing myocytes depended on whether myocytes were coupled to
      fibroblasts. In conclusion, univariate and multivariate sensitivity analyses are
      helpful tools to understand how Ca2+ cycling is impaired in HF and how this can
      be exacerbated by coupling of myocytes to fibroblasts. The design of
      pharmacological actions to restore normal activity should take into account the
      degree of fibrosis in the failing heart.

PMID- 30190678
TI  - The Regulation of Pulmonary Vascular Tone by Neuropeptides and the Implications
      for Pulmonary Hypertension.
AB  - Pulmonary hypertension (PH) is an incurable, chronic disease of small pulmonary
      vessels. Progressive remodeling of the pulmonary vasculature results in increased
      pulmonary vascular resistance (PVR). This causes secondary right heart failure.
      PVR is tightly regulated by a range of pulmonary vasodilators and constrictors.
      Endothelium-derived substances form the basis of most current PH treatments. This
      is particularly the case for pulmonary arterial hypertension. The major
      limitation of current treatments is their inability to reverse morphological
      changes. Thus, there is an unmet need for novel therapies to reduce the morbidity
      and mortality in PH. Microvessels in the lungs are highly innervated by sensory C
      fibers. Substance P and calcitonin gene-related peptide (CGRP) are released from
      C-fiber nerve endings. These neuropeptides can directly regulate vascular tone.
      Substance P tends to act as a vasoconstrictor in the pulmonary circulation and it
      increases in the lungs during experimental PH. The receptor for substance P,
      neurokinin 1 (NK1R), mediates increased pulmonary pressure. Deactivation of NK1R
      with antagonists, or depletion of substance P prevents PH development. CGRP is a
      potent pulmonary vasodilator. CGRP receptor antagonists cause elevated pulmonary
      pressure. Thus, the balance of these peptides is crucial within the pulmonary
      circulation (Graphical Abstract). Limited progress has been made in understanding
      their impact on pulmonary pathophysiology. This is an intriguing area of
      investigation to pursue. It may lead to promising new candidate therapies to
      combat this fatal disease. This review provides a summary of the current
      knowledge in this area. It also explores possible future directions for
      neuropeptides in PH.

PMID- 30190683
TI  - Increased Formation of Follicular Antrum in Aquaporin-8-Deficient Mice Is Due to
      Defective Proliferation and Migration, and Not Steroidogenesis of Granulosa
      Cells.
AB  - Aquaporin-8 (AQP8) is a water channel protein expressed exclusively in granulosa
      cells (GCs) in mouse ovary. Our previous studies of AQP8-deficient (AQP8-/-) mice
      demonstrated that AQP8 participates in folliculogenesis, including in the
      formation of follicles, ovulation, and atresia. However, its physiological
      function in formation of the antral follicle is still largely unknown. In the
      present study, we observed significantly increased numbers of antral follicles in
      AQP8-/- ovaries as well as significantly increased follicular antrum formation in
      in vitro 3D culture of AQP8-/- follicles. Functional detection of AQP8-/- GCs
      indicated that cell proliferation is impaired with FSH treatment, and wound
      healing and Transwell migration are also impaired with or without FSH treatment,
      compared with that in WT. However, the biosynthesis of estradiol and progesterone
      as well as the mRNA levels of key steroidogenic enzyme genes (CYP19A1 and StAR)
      in AQP8-/- GCs did not change, even with addition of FSH and/or testosterone. In
      order to estimate the influence of the impaired proliferation and migration on
      the density of GC mass, preantral follicles were injected with FITC-dextran,
      which distributes only in the intercellular space, and analyzed by confocal
      microscopy. The micrographs showed significantly higher transmission of
      fluorescence in AQP8-/- follicles, suggesting increased intercellular space of
      GCs. Based on this evidence, we concluded that AQP8 deficiency leads to increased
      formation of follicular antra in vivo and in vitro, and the mechanism may be
      associated with increased intercellular space of GCs, which may be caused by
      defective proliferation and migration of GCs. This study may offer new insight
      into the molecular mechanisms of the formation of follicular antrum.

PMID- 30190685
TI  - Full-Profile Pharmacokinetic Study of High Dose Baclofen in Subjects With Alcohol
      Use Disorder.
AB  - Baclofen a gamma amino-butyric acid type B (GABA-B) receptor agonist, which has
      raised some interest for the treatment of alcohol use disorder (AUD),
      occasionally at dose up to 300 mg/d. We conducted the first full-profile
      pharmacokinetic study on baclofen in AUD subjects, up to the oral daily dose of
      300 mg. Sixty subjects treated for AUD with marketed baclofen were enrolled in a
      prospective phase-1 study. Participants were divided into four dose groups (1:
      <60 mg/d; 2: 60-120 mg/d; 3: >120 mg/d-180 mg/d; and 4: >180 mg/d), and they
      underwent a full-profile pharmacokinetic analysis of baclofen, using a nonlinear
      mixed effects modeling. The influence of different clinical and biological
      covariates was assessed in an upward modeling. Fifty-seven participants completed
      the study (522 observed concentrations collected). Racemic baclofen showed a
      linear pharmacokinetic profile, corresponding to a one-compartment model, with no
      influencing clinical or biological factor. The pharmacokinetic parameters of
      baclofen were (bootstrap 95% confidence intervals): absorption constant (Ka) 1.64
      1/h (1.34-2), clearance (Cl/F) 11.6 L/h (10.8-12.3) and volume of distribution
      (Vd/F) 72.8 L (66.5-80.4) leading to a half-life of 4.4 h. The interindividual
      variability (IIV) was 44% (19-65), 21% (16-27), and 22% (11-36) for Ka, Cl/F, and
      Vd/F, respectively. The residual variability was 24% (21-26). No serious adverse
      event was reported. Registration: EudraCT #2013-003412-46.

PMID- 30190686
TI  - Growth Factor Proteins and Treatment-Resistant Depression: A Place on the Path to
      Precision.
AB  - Background: Since the neurotrophic hypothesis of depression was formulated,
      conflicting results have been reported regarding the role of growth factor
      proteins in depressed patients, including whether there are state or trait
      alterations found in patients compared to controls and whether they represent
      predictors of treatment response. Recently it has been hypothesized that
      heterogeneity of findings within this literature might be partly explained by
      participants' history of treatment-resistant depression. This study aimed to
      investigate the role of growth factor proteins in patients with treatment
      resistant depression (TRD) undergoing an inpatient intervention. Methods: Blood
      samples were collected from 36 patients with TRD and 36 matched controls.
      Patients were assessed both at admission and discharge from a specialist
      inpatient program. We examined serum biomarker differences between patients and
      non-depressed matched controls, longitudinal changes after inpatient treatment
      and relationship to clinical outcomes. Additionally, the influence of potential
      covariates on biomarker levels were assessed. Results: Patients displayed lower
      serum levels of brain-derived neurotrophic factor (OR = 0.025; 95% CI = 0.001,
      0.500) and vascular endothelial growth factor-C (VEGFC; OR = 0.083, 95% CI =
      0.008, 0.839) as well as higher angiopoietin-1 receptor (Tie2; OR = 2.651, 95% CI
      = 1.325, 5.303) compared to controls. Patients were stratified into responders
      (56%) and non-responders (44%). Lower VEGFD levels at admission predicted
      subsequent non-response (OR = 4.817, 95% CI = 1.247, 11.674). During treatment,
      non-responders showed a decrease in VEGF and VEGFC levels, while responders
      showed no significant changes. Conclusion: TRD patients demonstrate a deficit of
      peripheral growth factors and our results suggest that markers of the VEGF family
      might decline over time in chronically depressed patients in spite of
      multidisciplinary treatment. The action of angiogenic proteins may play an
      important role in the pathophysiology of TRD, and pending comprehensive
      investigation may provide important insights for the future of precision
      psychiatry.

PMID- 30190687
TI  - Stability of the Distribution of Patient Health Questionnaire-9 Scores Against
      Age in the General Population: Data From the National Health and Nutrition
      Examination Survey.
AB  - Background: Epidemiological studies using the nine-item Patient Health
      Questionnaire (PHQ-9) have reported inconsistencies regarding the relationship
      between age and total scores. To determine whether this discrepancy is due to the
      stability of the distribution of PHQ-9 total scores against age, we investigated
      whether the total score distribution remains stable during adulthood, and also
      investigated the mathematical patterns of the total score distribution. Methods:
      The present study utilized data from 15,847 participants of the 2009-2014 United
      States National Health and Nutrition Examination Survey, all of whom responded to
      all PHQ-9 items. The stability of the total score distribution among different
      age groups was examined using overlap coefficients and graphical analysis.
      Results: High overlap coefficients were observed between all age groups for the
      distributions of PHQ-9 total scores, suggesting that the distribution of PHQ-9
      total scores remains stable against age. Graphical analysis demonstrated that
      distributions of PHQ-9 total scores were similar across age groups. In addition,
      distributions of PHQ-9 total scores exhibited an exponential pattern, except at
      the lower end of the distribution. Conclusions: Our findings indicate that the
      stability of the distribution of PHQ-9 total scores throughout adulthood may
      underlie inconsistencies in the evidence regarding age-related changes in total
      depression scores.

PMID- 30190689
TI  - An Augmented Perceptual-Cognitive Intervention Using a Pattern Recall Paradigm
      With Junior Soccer Players.
AB  - In sport, perceptual skill training software is intended to assist tactical
      training in the field. The aim of this field study was to test whether
      "laboratory-based" pattern recall training would augment tactical skill training
      performed on the field. Twenty-six soccer players between 14 and 16 years of age
      from a single team participated in this study and were divided into three groups.
      The first received field training on a specific tactical skill plus cognitive
      training sessions on the pattern recall task. The second performed only the field
      training while the third group served as a control group and had field training
      on other topics. The task on the pre-, post-, and retention-tests was to recall
      specific soccer patterns displayed on a computer screen. Results showed
      significant changes between pre- and post-test performance. There was no
      significant interaction between groups and tests but the effect size was large.
      From pre- to retention-test, there was a significant difference between tests and
      an interaction between groups and tests, but no main effect difference between
      groups. On the basis of significance testing only retention was affected by the
      additional training, however, descriptive results and effect sizes from pre- to
      post-test were as expected and suggested there were learning benefits. Together
      these results indicate that augmented perceptual-cognitive training might be
      beneficial, but some limitations in our study design (e.g., missing field test,
      missing placebo group, etc.) need to be improved in future work.

PMID- 30190688
TI  - C-Reactive Protein as a Peripheral Biomarker in Schizophrenia. An Updated
      Systematic Review.
AB  - Objectives: The objective of this systematic review was to synthetize the
      published data on the relationships between elevated blood C-reactive protein
      (CRP) levels and schizophrenia (SZ) onset risk, illness characteristics and
      treatments, cognition and physical health. Method: The systematic bibliographic
      searches have been carried out according to the Cochrane methodology. Medline,
      web of science, Google Scholar with each database being searched from inception
      to November 2017. Results: 53 studies were included in the present review. While
      meta-analyses including case-control studies suggest a clear association between
      CRP and SZ, one other study has suggested that CRP-associated genes were
      associated with a lower risk of SZ onset. Increased CRP has been significantly
      associated with positive symptoms in acute phase psychosis, while studies
      including community-dwelling stabilized subjects did not find such an
      association. Abnormal CRP has been associated with a wide range of cognitive
      impairment in SZ stabilized individuals. Body Mass index has been extensively
      associated with increased CRP in SZ subjects; and increased CRP has been
      identified as a risk factor for metabolic syndrome and cardiovascular risk in SZ
      subjects. Increased CRP has also been associated with high nicotine dependence in
      SZ smokers and one study has suggested that increased CRP was associated with
      sedentary behavior. Conclusion: In the light of the above-mentioned studies,
      increased hs-CRP may be reasonably suggested as a marker for SZ onset risk, as
      well as a risk factor for increased positive symptoms, cognitive impairment,
      hypovitaminosis D, microbiota disturbances, cardiovascular and metabolic syndrome
      risk in SZ subjects, and increased nicotine dependence in SZ smokers. In case of
      increased CRP levels, anti-inflammatory strategies (add-on anti-inflammatory
      drugs including aspirin and omega 3 fatty acids, vitamin D supplementation,
      physical activity, probiotics) should be also further evaluated. Limits: Most of
      the studies were cross-sectional and cohort studies are needed to determine the
      temporal relationship between increased CRP and the psychiatric outcomes.

PMID- 30190690
TI  - Evidence That the Hormonal Contraceptive Pill Is Associated With Cosmetic Habits.
AB  - Hormonal contraception is known to cause subtle but widespread behavioral
      changes. Here, we investigated whether changes in cosmetic habits are associated
      with use of the hormonal contraceptive pill. We photographed a sample of women (N
      = 36) who self-reported whether or not they use the contraceptive pill, as well
      as their cosmetic habits. A separate sample of participants (N = 143) rated how
      much makeup these target women appeared to be wearing. We found that women not
      using the contraceptive pill (i.e., naturally cycling women) reported spending
      more time applying cosmetics for an outing than did women who use the
      contraceptive pill. We also found that the faces of these naturally cycling women
      were rated as wearing more cosmetics than the faces of the women using the
      contraceptive pill. Thus, we found clear associations between contraceptive pill
      use and makeup use. This provides evidence consistent with the possibility that
      cosmetic habits, and grooming behaviors more generally, are affected by hormonal
      contraception.

PMID- 30190691
TI  - Corrigendum: Biofunctional Understanding and Judgment of Size.
AB  - [This corrects the article DOI: 10.3389/fpsyg.2016.00436.].

PMID- 30190692
TI  - "When You Thought That There Is No One and Nothing": The Value of Psychodrama in
      Working With Abused Women.
AB  - This paper discusses how psychodrama methods and techniques can empower abused
      women and stimulate changes in their victim role. Through an in-depth
      exploration, we sought to gain an insider's perspective of the experiences of
      change and perceived outcomes for abused women, which could contribute to
      optimizing gender violence intervention. Theoretically, the study is grounded in
      the female co-responsibility and trans-generational transmission of women's
      victim role from mother to daughter. A mixed methods experimental design
      employing an explanatory sequential approach to data collection was implemented.
      A total sample of 33 abused women (15 in the experimental group, and 18 in the
      control group) was involved in studying the impact of a psychodrama intervention
      combined with an ecological intervention. Spontaneity and wellbeing, considered
      in this study as dimensions of empowerment, were measured. Phenomenological
      interviews were conducted with 7 women 3 months after the psychodrama
      intervention ended, and with 6 women 5 years later. Data was analyzed using the
      Interpretative Phenomenological Analysis method. The matrix of themes that
      emerged reflects four overarching themes: the victim, the group experience, the
      process of change, and the corollary of change. Benefits perceived by the women
      include trust, hope, increased self-esteem, empowering, and courage to make
      decisions and changes. Findings describe three paths of change for women who
      participated in an empowering-oriented psychodrama intervention program: the
      Proactive - Resilient type, the Active - Resistant type, and the Repetitive - Non
      Resilient type. Role-reconstruction and the interruption of trans-generational
      victim pattern were clear for the proactive type and possible for the active
      type, while the repetitive type showed minor changes but remained stuck in the
      victim pattern. As no claims to generalizability can be made, further research is
      needed to verify the proposed typology on larger samples. Psychodrama, as an
      action method, can empower abused women and has the potential to stimulate action
      in women's lives and initiate adaptive coping strategies leading to resilience.
      The study ends with several suggestions for assisted resilience specialists.

PMID- 30190693
TI  - Online Purchase Intention of Fruits: Antecedents in an Integrated Model Based on
      Technology Acceptance Model and Perceived Risk Theory.
AB  - Over recent years, online purchase platforms of fruits are increasingly emerged
      to advance the e-commerce development and improve quality of human life.
      Unfortunately, we empirically observed that a lot of enterprises selling fruits
      online have suffered from bankruptcy due to a lot of complicated factors, such as
      inefficient logistics, low acceptance of online platforms, and financial risks.
      One of the root causes responsible for such an unanticipated phenomenon is
      related to the purchase intention, which motivates us to investigate what are the
      dominant factors affecting the online purchase intention of fruits. The results
      can be of great significance to the development of fruit e-commerce enterprises
      in online marketing. Based on the technology acceptance model (TAM) and perceived
      risk theory (PRT), this research developed an integrated theoretical model to
      explore the influential factors underlying consumers' intention to purchase
      fruits online. A web-based survey of 344 consumers with ages below 30 was used to
      test the hypotheses in our theoretical model. Through sample collection with
      questionnaires, a structural equation model is developed to compute the coupling
      relationship between influential factors and purchase intention. The results
      reveal that fruit quality and price are dominantly affecting the willingness of
      consumers to purchase fruit. Surprisingly, we found that e-commerce platforms,
      information quality, and perceived risk are less significant. Finally, some
      specific suggestions are recommended for fruit e-commerce enterprises in devising
      effective marketing strategies.

PMID- 30190694
TI  - Language and Arithmetic: A Failure to Find Cross Cognitive Domain Semantic
      Priming Between Exception Phrases and Subtraction or Addition.
AB  - We examined cross-domain semantic priming effects between arithmetic and
      language. We paired subtractions with their linguistic equivalent, exception
      phrases (EPs) with positive quantifiers (e.g., "everybody except John") while
      pairing additions with their own linguistic equivalent, EPs with negative
      quantifiers (e.g., "nobody except John"; Moltmann, 1995). We hypothesized that
      EPs with positive quantifiers prime subtractions and inhibit additions while EPs
      with negative quantifiers prime additions and inhibit subtractions. Furthermore,
      we expected similar priming and inhibition effects from arithmetic into
      semantics. Our design allowed for a bidirectional analysis by using one trial's
      target as the prime for the next trial. Two experiments failed to show
      significant priming effects in either direction. Implications and possible
      shortcomings are explored in the general discussion.

PMID- 30190695
TI  - Autism Research: An Objective Quantitative Review of Progress and Focus Between
      1994 and 2015.
AB  - The nosology and epidemiology of Autism has undergone transformation following
      consolidation of once disparate disorders under the umbrella diagnostic, autism
      spectrum disorders. Despite this re-conceptualization, research initiatives,
      including the NIMH's Research Domain Criteria and Precision Medicine, highlight
      the need to bridge psychiatric and psychological classification methodologies
      with biomedical techniques. Combining traditional bibliometric co-word
      techniques, with tenets of graph theory and network analysis, this article
      provides an objective thematic review of research between 1994 and 2015 to
      consider evolution and focus. Results illustrate growth in Autism research since
      2006, with nascent focus on physiology. However, modularity and citation
      analytics demonstrate dominance of subjective psychological or psychiatric
      constructs, which may impede progress in the identification and stratification of
      biomarkers as endorsed by new research initiatives.

PMID- 30190697
TI  - Editorial: Emerging and Re-emerging Organizational Features, Work Transitions,
      and Occupational Risk Factors: The Good, the Bad, the Right. An Interdisciplinary
      Perspective.

PMID- 30190696
TI  - Relationships Between Accuracy in Predicting Direction of Gravitational Vertical
      and Academic Performance and Physical Fitness in Schoolchildren.
AB  - Enhanced levels of cardio-respiratory fitness (CRF) and physical activity (PA)
      are both positively associated with health and academic outcomes, but less is
      known about the spatial processing and perceptual components of PA. Perception of
      vertical (PV) is a spatial orientation ability that is important for PA, and is
      usually measured as relative accuracy in aligning an object to gravitational
      vertical against a tilted background. However, evidence is inconclusive regarding
      the relationship of PV to educational outcomes - most importantly, numeracy.
      Students were recruited from primary schools in the Australian Capital Territory.
      A group of 341 (females n = 162, mean age 11.3 years) children performed all the
      tests required for this study. A computerised rod and frame test of PV employing
      a small (20 degrees ) visual angle was administered, and socio-economic status
      (SES), national education test results (NAPLAN, 2010), and CRF and PA data were
      collected. Correlation and hierarchical regression analysis were used to examine
      the inter-relationships between PV and CRF, PA, SES and NAPLAN results. The two
      extreme quartile score groups from the measures of PV, PA and CRF were examined
      in relation to NAPLAN scores. PV scores arising from testing with a small visual
      angle and SES were found to be significantly associated with overall academic
      scores, and with the Numeracy, Reading, and Writing components of academic
      performance. Female gender was significantly associated with Writing score, and
      male with Numeracy score. Being less influenced by the background tilted frame,
      and therefore having visual field independence (FI), was associated with
      significantly higher academic scores, with the largest effect in Numeracy scores
      (effect size, d = 0.82) and also associated with higher CRF and PA levels. FI was
      positively associated with all the academic modules examined, and most strongly
      with Numeracy test results, suggesting that FI provides an indicator of STEM
      ability. These findings suggest that further longitudinal research into
      strategies designed to enhance visual FI deserve consideration, with a focus on
      specialized PA programs for pre-pubescent children. It is possible that small
      visual angle spatial tasks during PA may stimulate neural networks involved in
      numerical cognition.

PMID- 30190698
TI  - Freud's Dream Interpretation: A Different Perspective Based on the Self
      Organization Theory of Dreaming.

PMID- 30190699
TI  - The Body Speaks: Using the Mirror Game to Link Attachment and Non-verbal
      Behavior.
AB  - The Mirror Game (MG) is a common exercise in dance/movement therapy and drama
      therapy. It is used to promote participants' ability to enter and remain in a
      state of togetherness. In spite of the wide use of the MG by practitioners, it is
      only recently that scientists begun to use the MG in research, examining its
      correlates, validity, and reliability. This study joins this effort by reporting
      on the identification of scale items to describe the non-verbal behavior
      expressed during the MG and its correlation to measures of attachment. Thus, we
      explored the application of the MG as a tool for assessing the embodiment of
      attachment in adulthood. Forty-eight participants (22 females, mean age = 33.2)
      played the MG with the same gender-matched expert players. All MG were
      videotaped. In addition, participants were evaluated on two central measurements
      of attachment in adulthood: The Adult Attachment Interview (AAI) and the
      Experience in Close Relationship questionnaire (ECR). To analyze the data, we
      developed the "MG scale" that coded the non-verbal behavior during the movement
      interaction, using 19 parameters. The sub-scales were reduced using factor
      analysis into two dimensions referred to as "together" and "free." The free
      factor was significantly correlated to both measurements of attachment:
      Participants classified as having secure attachment on the AAI, received higher
      scores on the MG free factor than participants classified as insecure [t(46) =
      7.858, p = 0.000]. Participants, who were high on the avoidance dimension on the
      ECR, were low on the MG free factor [r(48) = -0.285, p = 0.007]. This is the
      first study to examine the MG as it is used by practitioners and its correlation
      to highly standardized measures. This exploratory study may be considered as part
      of the first steps of exploring the MG as a standardized assessment tool. The
      advantages of the MG as a simple, non-verbal movement interaction demonstrate
      some of the strengths of dance/movement and drama therapy practice.

PMID- 30190701
TI  - Application of Precision Medicine in Neurodegenerative Diseases.
AB  - One of the main challenges for healthcare systems is the increasing prevalence of
      neurodegenerative pathologies together with the rapidly aging populations. The
      enormous progresses made in the field of biomedical research and informatics have
      been crucial for improving the knowledge of how genes, epigenetic modifications,
      aging, nutrition, drugs and microbiome impact health and disease. In fact, the
      availability of high technology and computational facilities for large-scale
      analysis enabled a deeper investigation of neurodegenerative disorders, providing
      a more comprehensive overview of disease and encouraging the development of a
      precision medicine approach for these pathologies. On this subject, the creation
      of collaborative networks among medical centers, research institutes and highly
      qualified specialists can be decisive for moving the precision medicine from the
      bench to the bedside. To this purpose, the present review has been thought to
      discuss the main components which may be part of precise and personalized
      treatment programs applied to neurodegenerative disorders. Parkinson Disease will
      be taken as an example to understand how precision medicine approach can be
      clinically useful and provide substantial benefit to patients. In this
      perspective, the realization of web-based networks can be decisive for the
      implementation of precision medicine strategies across different specialized
      centers as well as for supporting clinical/therapeutical decisions and promoting
      a more preventive and participative medicine for neurodegenerative disorders.
      These collaborative networks are essentially addressed to find innovative,
      sustainable and effective strategies able to provide optimal and safer therapies,
      discriminate at risk individuals, identify patients at preclinical or early stage
      of disease, set-up individualized and preventative strategies for improving
      prognosis and patient's quality of life.

PMID- 30190700
TI  - Occulomotor Neural Integrator Dysfunction in Multiple Sclerosis: Insights From
      Neuroimaging.
AB  - Background: Magnetic resonance imaging is a key diagnostic and monitoring tool in
      multiple Sclerosis (MS). While the substrates of motor and neuropsychological
      symptoms in MS have been extensively investigated, nystagmus-associated imaging
      signatures are relatively under studied. Accordingly, the objective of this study
      is the comprehensive characterisation of cortical, subcortical, and brainstem
      involvement in a cohort of MS patients with gaze-evoked nystagmus. Methods:
      Patients were recruited from a specialist MS clinic and underwent multimodal
      neuroimaging including high-resolution structural and diffusion tensor data
      acquisitions. Morphometric analyses were carried out to evaluate patterns of
      cortical, subcortical, brainstem, and cerebellar gray matter pathology.
      Volumetric analyses were also performed to further characterize subcortical gray
      matter degeneration. White matter integrity was evaluated using axial-, mean-,
      and radial diffusivity as well as fractional anisotropy. Results: Whole-brain
      morphometry highlighted considerable brainstem and cerebellar gray matter
      atrophy, and the tract-wise evaluation of white matter metrics revealed
      widespread pathology in frontotemporal and parietal regions. Nystagmus-associated
      gray matter degeneration was identified in medial cerebellar, posterior medullar,
      central pontine, and superior collicular regions. Volume reductions were
      identified in the putamen, thalamus and hippocampus. Conclusions: Multiple
      sclerosis is associated with widespread gray matter pathology which is not
      limited to cortical regions but involves striatal, thalamic, cerebellar, and
      hippocampal foci. The imaging signature of gaze-evoked nystagmus in MS confirms
      the degeneration of key structures of the neural integrator network.

PMID- 30190702
TI  - Switching From Glargine to Degludec: The Effect on Metabolic Control and Safety
      During 1-Year of Real Clinical Practice in Children and Adolescents With Type 1
      Diabetes.
AB  - Background/Objective: Insulin degludec (IDeg) is an ultra-long-acting analog with
      less daily variability compared to other basal insulins. In this retrospective
      study we examined 1-year efficacy and safety of IDeg in youth with type 1
      diabetes (T1D). Subjects/Methods: Thirty-seven patients [11.7 +/- 4.22 years; T1D
      duration 4.97 +/- 3.63 years; once-daily glargine (IGlar) by at least 1 year]
      were switched to once-daily IDeg because of glycosylated hemoglobin (HbA1c) >7.5%
      and/or reported physical pain at IGlar injection. Changes in HbA1c, 30-day mean
      fasting plasma glucose (mean FPG), daily insulin dose, and severe hypoglycemia
      rates were collected at basal insulin switch (T0), 3-months (T1), 6-months (T2),
      and 12-months (T3) after IDeg was started. Results: In patients with HbA1c >7.5%
      at T0 we found a decrease in HbA1c values (%) from 8.46 +/- 0.53 to 7.89 +/- 0.72
      at T1 (p = 0.008) and 7.97 +/- 0.89 at T2 (p = 0.035). At T3, 38.9% of patients
      had HbA1c <= 7.5%. Mean FPG levels significantly decreased at T2 (p = 0.043). In
      the overall study population, we documented an increase in IDeg dose (+12.5% at
      T3; p < 0.001) and a decrease in mealtime insulin dose (-11.6% at T3; p = 0.001)
      after switch. HbA1c levels were unchanged. No episode of severe hypoglycemia was
      reported. Conclusions: Our data in children and adolescents with T1D suggest that
      IDeg dose should be increased by 12% and mealtime insulin doses should be lowered
      by 11% for patients who previously received IGlar. IDeg might be considered
      useful and well tolerated and it seems to improve the glycemic control compared
      to IGlar, mainly in patients with poor glycemic control.

PMID- 30190704
TI  - Long-Term l-Serine Administration Reduces Food Intake and Improves Oxidative
      Stress and Sirt1/NFkappaB Signaling in the Hypothalamus of Aging Mice.
AB  - Serine has recently been shown to reduce oxidative stress and inflammation,
      which, when occurring in the hypothalamus, contribute to age-related obesity. To
      explore whether long-term serine administration reduces oxidative stress and body
      weight in aging mice, various concentrations of l-serine dissolved in water were
      administered to 18-month-old C57BL/6J mice for 6 months. The results showed that
      the administration of 0.5% (w/v) l-serine significantly reduced food intake and
      body weight gain during the experiment. Moreover, the administration of 0.5% l
      serine decreased the concentrations of leptin, malondialdehyde, interleukin
      1beta, and interleukin-6, while it increased those of superoxide dismutase and
      glutathione, in both the serum and hypothalamus. Reactive oxygen species and the
      activity of nicotinamide adenine dinucleotide phosphate oxidase were reduced in
      the hypothalamus of aging mice treated with l-serine as compared with untreated
      control mice. Additionally, the expression of the leptin receptor increased while
      the levels of neuropeptide Y and agouti-related protein decreased in mice that
      had been treated with 0.5% l-serine. The expression of Sirt1 and phosphorylated
      signal transducers and activators of transcription 3 (pSTAT3) increased, while
      that of phosphorylated NFkappaB decreased in the mice treated with 0.5% l-serine.
      These results indicated that long-term l-serine administration reduces body
      weight by decreasing orexigenic peptide expression and reduces oxidative stress
      and inflammation during aging in mice, possibly by modulating the Sirt1/NFkappaB
      pathway. Thus, l-serine has the potential to be used in the prevention of age
      related obesity.

PMID- 30190703
TI  - Estrogen Receptor Beta-Mediated Modulation of Lung Cancer Cell Proliferation by
      27-Hydroxycholesterol.
AB  - 27-hydroxycholesterol (27HC) is an abundant cholesterol metabolite in human
      circulation and promotes breast cancer cell proliferation. Although lung is one
      of the organs that contain high levels of 27HC, the role of 27HC in lung is
      unknown. In this study, we found that 27HC promotes lung cancer cell
      proliferation in an estrogen receptor beta (ERbeta)-dependent manner. The
      expression of 27HC-generating enzyme CYP27A1 is higher in lung cancer cells than
      in normal lung cells. Treatment with 27HC increased cell proliferation in ERbeta
      positive lung cancer cells, but not in ERalpha-positive or ER-negative cells. The
      effect on cell proliferation is specific to 27HC and another oxysterol, 25
      hydroxycholesterol that has a similar oxysterol structure with 27HC. Moreover,
      among ligands for nuclear receptors tested, only estrogen had the proliferative
      effect, and the effect by 27HC and estrogen was inhibited by ERbeta-specific, but
      not ERalpha-specific, inhibitors. In addition, the effect by 27HC was not
      affected by membrane-bound estrogen receptor GPR30. Interestingly, despite the
      high expression of CYP27A1, endogenously produced 27HC was not the major
      contributor of the 27HC-induced cell proliferation. Using kinase inhibitors, we
      found that the effect by 27HC was mediated by the PI3K-Akt signaling pathway.
      These results suggest that 27HC promotes lung cancer cell proliferation via
      ERbeta and PI3K-Akt signaling. Thus, lowering 27HC levels may lead to a novel
      approach for the treatment of lung cancer.

PMID- 30190705
TI  - Oxyhemoglobin Saturation Overshoot Following Obstructive Breathing Events
      Mitigates Sleep Apnea-Induced Glucose Elevations.
AB  - Background: Obstructive sleep apnea (OSA) and nocturnal hypoxia are associated
      with disturbances in glucose regulation and diabetes. Temporal associations
      between OSA, oxygenation profiles and glucose have not been well-described. We
      hypothesized that oxyhemoglobin desaturation during apneic events and subsequent
      post-apnea saturation overshoot predict nocturnal glucose. Methods: In 30 OSA
      patients who underwent polysomnography while subjected to CPAP withdrawal, we
      characterized SPO2 swings by frequency, desaturation depth, and overshoot height
      relative to baseline. We examined the associations between frequently sampled
      glucose and SPO2 swings during the preceding 10 min. We developed multi-variable
      mixed effects linear regression to examine the independent associations between
      glucose and each level of these SPO2 swings, while controlling for OSA severity.
      Results: Desaturation depth was not associated with glucose (p > 0.05). In
      contrast, overshoot was associated with glucose in a dose-dependent manner. Each
      SPO2 peak that did not rise to within 1% of baseline was associated with
      incremental glucose elevations of 0.49 mg/dL (p = 0.01), whereas peaks that
      exceeded baseline by >1% were associated with glucose reductions of 0.46 mg/dL.
      Overshoot remained an independent predictor of glucose after adjustment for mean
      SPO2 and OSA severity (p > 0.05). Conclusions: Vigorous SPO2 improvements after
      apneic events may protect patients against OSA-related glucose elevations.

PMID- 30190706
TI  - Genetic Factors Affecting Seasonality, Mood, and the Circadian Clock.
AB  - In healthy humans, seasonality has been documented in psychological variables,
      chronotype, sleep, feeding, metabolic and autonomic function, thermoregulation,
      neurotransmission, and hormonal response to stimulation, thus representing a
      relevant factor to account for, especially when considering the individual
      susceptibility to disease. Mood is largely recognized as one of the central
      aspects of human behavior influenced by seasonal variations. This historical
      notion, already mentioned in ancient medical reports, has been recently confirmed
      by fMRI findings, which showed that seasonality in human cognitive brain
      functions may influence affective control with annual variations. Thus,
      seasonality plays a major role in mood disorders, affecting psychopathology, and
      representing the behavioral correlate of a heightened sensitivity to factors
      influencing circannual rhythms in patients. Although the genetic basis of
      seasonality and seasonal affective disorder (SAD) has not been established so
      far, there is growing evidence that factors affecting the biological clock, such
      as gene polymorphisms of the core clock machinery and seasonal changes of the
      light-dark cycle, exert a marked influence on the behavior of patients affected
      by mood disorders. Here we review recent findings about the effects of individual
      gene variants on seasonality, mood, and psychopathological characteristics.

PMID- 30190707
TI  - Temperature Driven Changes in Benthic Bacterial Diversity Influences
      Biogeochemical Cycling in Coastal Sediments.
AB  - Marine sediments are important sites for global biogeochemical cycling, mediated
      by macrofauna and microalgae. However, it is the microorganisms that drive these
      key processes. There is strong evidence that coastal benthic habitats will be
      affected by changing environmental variables (rising temperature, elevated CO2),
      and research has generally focused on the impact on macrofaunal biodiversity and
      ecosystem services. Despite their importance, there is less understanding of how
      microbial community assemblages will respond to environmental changes. In this
      study, a manipulative mesocosm experiment was employed, using next-generation
      sequencing to assess changes in microbial communities under future environmental
      change scenarios. Illumina sequencing generated over 11 million 16S rRNA gene
      sequences (using a primer set biased toward bacteria) and revealed Bacteroidetes
      and Proteobacteria dominated the total bacterial community of sediment samples.
      In this study, the sequencing coverage and depth revealed clear changes in
      species abundance within some phyla. Bacterial community composition was
      correlated with simulated environmental conditions, and species level community
      composition was significantly influenced by the mean temperature of the
      environmental regime (p = 0.002), but not by variation in CO2 or diurnal
      temperature variation. Species level changes with increasing mean temperature
      corresponded with changes in NH4 concentration, suggesting there is no functional
      redundancy in microbial communities for nitrogen cycling. Marine coastal
      biogeochemical cycling under future environmental conditions is likely to be
      driven by changes in nutrient availability as a direct result of microbial
      activity.

PMID- 30190708
TI  - Intensified Pulse Rotations Buildup Pea Rhizosphere Pathogens in Cereal and Pulse
      Based Cropping Systems.
AB  - The association of plants and microbial communities is crucial for crop
      production, and host plants influence the composition of rhizosphere microbiomes.
      Pulse crops play an important role in the development of sustainable cropping
      systems, and producers in the Canadian prairies often increase the frequency of
      pulses in their cropping systems. In this study, we determined the shifts in the
      fungal community of pea (Pisum sativum L.) rhizosphere, as influenced by the
      frequency of pulses in rotation, using high throughput sequencing. Six cropping
      systems containing pea (P), lentil (Lens culinaris Medik., L), hybrid canola
      (Brassica napus L., C), wheat (Triticum aestivum L., W), and oat (Avena sativa
      L., O) in different intensities were tested. The fungal communities were assessed
      at the flowering stage in the fourth and fifth year of the 4-year rotations.
      Cropping system had a significant impact on the composition of the rhizosphere
      fungal community, and the effect of crop rotation sequence was greater and
      explained more of the variation than the effect of previous crops. The rotation
      with consecutive pulses (WPLP) decreased fungal evenness and increased the
      proportion of pathotrophs. Fusarium was a dominant and ubiquitous pathotrophic
      genus. Olpidium virulentus, Botrytis cinerea, Fusarium solani, F. graminearum,
      and Alternaria eichhorniae were generally more abundant in pulse intensive
      rotations (WPLP, WLOP, and WPOP), the exception being F. solani which was not
      promoted by lentil. Reads of O. virulentus and B. cinerea were most abundant in
      pea preceded by lentil followed by the reads of Mortierella elongata in pea
      preceded by wheat. Pea consistently had higher grain yield when grown in
      diversified rotations including wheat, canola/lentil, and oat than rotations with
      two repeated crops (canola or pea). Cropping system affected the soil
      physicochemical properties, and soil pH was the main driver of fungal community
      shift. No evidence of beneficial microorganisms involvement in plant productivity
      was observed, but the high abundance of pathotrophs in pulse intensified
      rotations suggests the possibility of pathogen buildup in the soil with
      increasing pulse frequency. Diversifying rotation sequences minimized disease
      risk and increased pea production, in this study. Careful selection of plant
      species appears as a strategy for the management of rhizosphere fungal
      communities and the maintenance of crop production system's health.

PMID- 30190709
TI  - Enterotoxin Production of Bacillus thuringiensis Isolates From Biopesticides,
      Foods, and Outbreaks.
AB  - While the relevance of Bacillus (B.) cereus as a major cause of gastroenteritis
      is undisputed, the role of the closely related B. thuringiensis in foodborne
      disease is unclear. B. thuringiensis strains frequently harbor enterotoxin genes.
      However, the organism has only very rarely been associated with foodborne
      outbreaks, possibly due to the fact that during outbreak investigations, B.
      cereus is routinely not differentiated from B. thuringiensis. A recent EFSA
      scientific opinion stresses the urgent need for further data allowing for
      improved risk assessment, in particular as B. thuringiensis is a commonly used
      biopesticide. Therefore, the aim of this study was to gain further insights into
      the hazardous potential of B. thuringiensis. To this end, 39 B. thuringiensis
      isolates obtained from commercially used biopesticides, various food sources, as
      well as from foodborne outbreaks were characterized by panC typing, panC-based
      SplitsTree analysis, toxin gene profiling, FTIR spectroscopic analysis, a
      cytotoxicity assay screening for enterotoxic activity, and a sphingomyelinase
      assay. The majority of the tested B. thuringiensis isolates exhibited low (23%, n
      = 9) or mid level enterotoxicity (74%, n = 29), and produced either no (59%, n =
      23) or low levels (33%, n = 13) of sphingomyelinase, which is reported to act
      synergistically with enterotoxins Nhe and Hbl. One strain isolated from rosemary
      was however classified as highly enterotoxic surpassing the cytotoxic activity of
      the high-level reference strain by a factor of 1.5. This strain also produced
      vast amounts of sphingomyelinase. Combining all results obtained in this study
      into a fingerprint pattern, several enterotoxic biopesticide strains were
      indistinguishable from those of isolates from foods or collected in association
      with outbreaks. Our study shows that many B. thuringiensis biopesticide strains
      exhibit mid-level cytotoxicity in a Vero cell assay and that some of these
      strains cannot be differentiated from isolates collected from foods or in
      association with outbreaks. Thus, we demonstrate that the use of B. thuringiensis
      strains as biopesticides can represent a food safety risk, underpinning the
      importance of assessing the hazardous potential of each strain and formulation
      used.

PMID- 30190710
TI  - Endophytic Bacterial Community Structure and Function of Herbaceous Plants From
      Petroleum Hydrocarbon Contaminated and Non-contaminated Sites.
AB  - Bacterial endophytes (BEs) are non-pathogenic residents of healthy plant tissues
      that can confer benefits to plants. Many Bacterial endophytes have been shown to
      contribute to plant growth and health, alleviation of plant stress and to in
      planta contaminant-degradation. This study examined the endophytic bacterial
      communities of plants growing abundantly in a heavily hydrocarbon contaminated
      site, and compared them to those found in the same species at a non-contaminated.
      We used culture- dependent and independent methods to characterize the community
      structure, hydrocarbon degrading capabilities, and plant growth promoting traits
      of cultivable endophytes isolated from Achillea millefolium, Solidago Canadensis,
      and Daucus carota plants from these two sites. Culture- dependent and independent
      analyses revealed class Gammaproteobacteria predominated in all the plants
      regardless of the presence of petroleum hydrocarbon, with Pantoea spp. as largely
      dominant. It was interesting to note a >50% taxonomic overlap (genus level) of
      16s rRNA high throughput amplicon sequences with cultivable endophytes. PERMANOVA
      analysis of TRFLP fragments revealed significant structural differences between
      endophytic bacterial communities from hydrocarbon-contaminated and non
      contaminated soils-however, there was no marked difference in their functional
      capabilities. Pantoea spp. demonstrated plant beneficial characteristics, such as
      P solubilization, indole-3-acetic acid production and presence of 1
      aminocyclopropane-1-carboxylate deaminase. Our findings reveal that functional
      capabilities of bacterial isolates being examined were not influenced by the
      presence of contamination; and that the stem endosphere supports ubiquitous BEs
      that were consistent throughout plant hosts and sites.

PMID- 30190711
TI  - Isotope-Assisted Metabolite Analysis Sheds Light on Central Carbon Metabolism of
      a Model Cellulolytic Bacterium Clostridium thermocellum.
AB  - Cellulolytic bacteria have the potential to perform lignocellulose hydrolysis and
      fermentation simultaneously. The metabolic pathways of these bacteria, therefore,
      require more comprehensive and quantitative understanding. Using isotope tracer,
      gas chromatography-mass spectrometry, and metabolic flux modeling, we decipher
      the metabolic network of Clostridium thermocellum, a model cellulolytic bacterium
      which represents as an attractive platform for conversion of lignocellulose to
      dedicated products. We uncover that the Embden-Meyerhof-Parnas (EMP) pathway is
      the predominant glycolytic route whereas the Entner-Doudoroff (ED) pathway and
      oxidative pentose phosphate pathway are inactive. We also observe that C.
      thermocellum's TCA cycle is initiated by both Si- and Re-citrate synthase, and it
      is disconnected between 2-oxoglutarate and oxaloacetate in the oxidative
      direction; C. thermocellum uses a citramalate shunt to synthesize isoleucine; and
      both the one-carbon pathway and the malate shunt are highly active in this
      bacterium. To gain a quantitative understanding, we further formulate a fluxome
      map to quantify the metabolic fluxes through central metabolic pathways. This
      work represents the first global in vivo investigation of the principal carbon
      metabolism of C. thermocellum. Our results elucidate the unique structure of
      metabolic network in this cellulolytic bacterium and demonstrate the capability
      of isotope-assisted metabolite studies in understanding microbial metabolism of
      industrial interests.

PMID- 30190713
TI  - Iohexol Degradation by Biogenic Palladium Nanoparticles Hosted in Anaerobic
      Granular Sludge.
AB  - To improve the degradation ability of anaerobic granular sludge (AGS) toward the
      iodinated contrast media (ICM) iohexol, biogenic nanoscale palladium (Pd) was
      formed in AGS via microbial reduction. The Pd hosted in AGS (Pd-AGS) was used for
      iohexol degradation. The effects of the electron donor, reaction medium, iodide
      ion fouling, and polymer embedding of the Pd-AGS on the reactivity were
      investigated. Our results showed the Pd-AGS increased the degradation rate of
      iohexol, with a conversion rate constant increased by 86.3-fold compared to the
      AGS control. Various organic compounds were investigated as electron donors to
      initiate the catalytic activity of Pd-AGS and the promotion achieved with the
      tested electron donors was in the following order: formate > lactate > ethanol >
      glucose > acetate. The Pd-AGS had high reactivity in deionized water at mild pH,
      and almost no reactivity under acidic (pH = 1.2) and alkaline (pH > 11)
      conditions. The presence of iodide ions in the medium inhibited the catalytic
      activity of Pd-AGS toward iohexol because of catalyst fouling. Embedding the Pd
      AGS in alginate, chitosan, or polyvinyl alcohol (PVA) could prevent Pd loss but
      it also retarded the iohexol degradation rate. The Pd-AGS, as a combination of Pd
      catalyst and AGS, provides a novel strategy for iohexol degradation in polluted
      water and wastewater.

PMID- 30190714
TI  - VmPacC Is Required for Acidification and Virulence in Valsa mali.
AB  - The role of the transcription factor PacC has been characterised in several
      pathogenic fungi, and it affects virulence via several mechanisms. In this study,
      we examined the role of the PacC homolog VmPacC in Valsa mali, the causal agent
      of apple canker disease. We found that the expression of VmPacC was up-regulated
      in neutral and alkaline pH and during infection. At pH 6-10, the radial growth of
      a VmPacC deletion mutant decreased compared to wild-type. In addition, the
      sensitivity to oxidative stress of the VmPacC deletion mutant was impaired, as
      its growth was more severely inhibited by H2O2 than that of the wild-type. The
      lesion size caused by the VmPacC deletion mutant was smaller than that of the
      wild-type on apple leaves and twigs. Interestingly, expression of pectinase genes
      increased in deletion mutant during infection. To further confirm the negative
      regulation, we generated dominant activated C-27 allele mutants that
      constitutively express VmPacC. The pectinase activity of activated mutants was
      reduced at pH 4. We further observed that V. mali can acidify the pH during
      infection, and that the capacity for acidification was impaired after VmPacC
      deletion. Furthermore, VmPacC is involved in the generation of citric acid, which
      affects virulence. These results indicate that VmPacC is part of the fungal
      responses to neutral and alkaline pH and oxidative stress. More importantly,
      VmPacC is required for acidification of its environment and for full virulence in
      V. mali.

PMID- 30190715
TI  - Microbial Community and in situ Bioremediation of Groundwater by Nitrate Removal
      in the Zone of a Radioactive Waste Surface Repository.
AB  - The goal of the present work was to investigate the physicochemical and
      radiochemical conditions and the composition of the microbial community in the
      groundwater of a suspended surface repository for radioactive waste (Russia) and
      to determine the possibility of in situ groundwater bioremediation by removal of
      nitrate ions. Groundwater in the repository area (10-m depth) had elevated
      concentrations of strontium, tritium, nitrate, sulfate, and bicarbonate ions.
      High-throughput sequencing of the V3-V4/V4 region of the 16S rRNA gene revealed
      the presence of members of the phyla Proteobacteria (genera Acidovorax,
      Simplicispira, Thermomonas, Thiobacillus, Pseudomonas, Brevundimonas, and
      uncultured Oxalobacteraceae), Firmicutes (genera Bacillus and Paenibacillus), and
      Actinobacteria (Candidatus Planktophila, Gaiella). Canonical correspondence
      analysis suggested that major contaminant - nitrate, uranium, and sulfate shaped
      the composition of groundwater microbial community. Groundwater samples contained
      culturable aerobic organotrophic, as well as anaerobic fermenting, iron-reducing,
      and denitrifying bacteria. Pure cultures of 33 bacterial strains belonging to 15
      genera were isolated. Members of the genera Pseudomonas, Rhizobium, Cupriavidus,
      Shewanella, Ensifer, and Thermomonas reduced nitrate to nitrite and/or
      dinitrogen. Application of specific primers revealed the nirS and nirK genes
      encoding nitrite reductases in bacteria of the genera Pseudomonas, Rhizobium, and
      Ensifer. Nitrate reduction by pure bacterial cultures resulted in decreased
      ambient Eh. Among the organic substrates tested, sodium acetate and milk whey
      were the best for stimulation of denitrification by the microcosms with
      groundwater microorganisms. Injection of these substrates into the subterranean
      horizon (single-well push-pull test) resulted in temporary removal of nitrate
      ions in the area of the suspended radioactive waste repository and confirmed the
      possibility for in situ application of this method for bioremediation.

PMID- 30190712
TI  - Food-Associated Stress Primes Foodborne Pathogens for the Gastrointestinal Phase
      of Infection.
AB  - The incidence of foodborne outbreaks and product recalls is on the rise. The
      ability of the pathogen to adapt and survive under stressful environments of food
      processing and the host gastrointestinal tract may contribute to increasing
      foodborne illnesses. In the host, multiple factors such as bacteriolytic enzymes,
      acidic pH, bile, resident microflora, antimicrobial peptides, and innate and
      adaptive immune responses are essential in eliminating pathogens. Likewise, food
      processing and preservation techniques are employed to eliminate or reduce human
      pathogens load in food. However, sub-lethal processing or preservation treatments
      may evoke bacterial coping mechanisms that alter gene expression, specifically
      and broadly, resulting in resistance to the bactericidal insults. Furthermore,
      environmentally cued changes in gene expression can lead to changes in bacterial
      adhesion, colonization, invasion, and toxin production that contribute to
      pathogen virulence. The shared microenvironment between the food preservation
      techniques and the host gastrointestinal tract drives microbes to adapt to the
      stressful environment, resulting in enhanced virulence and infectivity during a
      foodborne illness episode.

PMID- 30190716
TI  - Leafhopper-Induced Activation of the Jasmonic Acid Response Benefits Salmonella
      enterica in a Flagellum-Dependent Manner.
AB  - Enteric human pathogens such as Salmonella enterica are typically studied in the
      context of their animal hosts, but it has become apparent that these bacteria
      spend a significant portion of their life cycle on plants. S. enterica survives
      the numerous stresses common to a plant niche, including defense responses, water
      and nutrient limitation, and exposure to UV irradiation leading to an increased
      potential for human disease. In fact, S. enterica is estimated to cause over one
      million cases of foodborne illness each year in the United States with 20% of
      those cases resulting from consumption of contaminated produce. Although S.
      enterica successfully persists in the plant environment, phytobacterial infection
      by Pectobacterium carotovorum or Xanthomonas spp. increases S. enterica survival
      and infrequently leads to growth on infected plants. The co-association of
      phytophagous insects, such as the Aster leafhopper, Macrosteles quadrilineatus,
      results in S. enterica populations that persist at higher levels for longer
      periods of time when compared to plants treated with S. enterica alone. We
      hypothesized that leafhoppers increase S. enterica persistence by altering the
      plant defense response to the benefit of the bacteria. Leafhopper infestation
      activated the jasmonic acid (JA) defense response while S. enterica colonization
      triggered the salicylic acid (SA) response. In tomato plants co-treated with S.
      enterica and leafhoppers, both JA- and SA-inducible genes were activated,
      suggesting that the presence of leafhoppers may affect the crosstalk that occurs
      between the two immune response pathways. To rule out the possibility that
      leafhoppers provide additional benefits to S. enterica, plants were treated with
      a chemical JA analog to activate the immune response in the absence of
      leafhoppers. Although bacterial populations continue to decline over time, analog
      treatment significantly increased bacterial persistence on the leaf surface.
      Bacterial mutant analysis determined that the bacterial flagellum, whether
      functional or not, was required for increased S. enterica survival after analog
      treatment. By investigating the interaction between this human pathogen, a common
      phytophagous insect, and their plant host, we hope to elucidate the mechanisms
      promoting S. enterica survival on plants and provide information to be used in
      the development of new food safety intervention strategies.

PMID- 30190717
TI  - Pre-clinical Imaging of Invasive Candidiasis Using ImmunoPET/MR.
AB  - The human commensal yeast Candida is the fourth most common cause of hospital
      acquired bloodstream infections, with Candida albicans accounting for the
      majority of the >400,000 life-threatening infections annually. Diagnosis of
      invasive candidiasis (IC), a disease encompassing candidemia (blood-borne yeast
      infection) and deep-seated organ infections, is a major challenge since clinical
      manifestations of the disease are indistinguishable from viral, bacterial and
      other fungal diseases, and diagnostic tests for biomarkers in the bloodstream
      such as PCR, ELISA, and pan-fungal beta-D-glucan lack either standardization,
      sensitivity, or specificity. Blood culture remains the gold standard for
      diagnosis, but test sensitivity is poor and turn-around time slow. Furthermore,
      cultures can only be obtained when the yeast resides in the bloodstream, with
      samples recovered from hematogenous infections often yielding negative results.
      Consequently, there is a pressing need for a diagnostic test that allows the
      identification of metastatic foci in deep-seated Candida infections, without the
      need for invasive biopsy. Here, we report the development of a highly specific
      mouse IgG3 monoclonal antibody (MC3) that binds to a putative beta-1,2-mannan
      epitope present in high molecular weight mannoproteins and phospholipomannans on
      the surface of yeast and hyphal morphotypes of C. albicans, and its use as a
      [64Cu]NODAGA-labeled tracer for whole-body pre-clinical imaging of deep-seated C.
      albicans infections using antibody-guided positron emission tomography and
      magnetic resonance imaging (immunoPET/MRI). When used in a mouse intravenous
      (i.v.) challenge model that faithfully mimics disseminated C. albicans infections
      in humans, the [64Cu]NODAGA-MC3 tracer accurately detects infections of the
      kidney, the principal site of blood-borne candidiasis in this model. Using a
      strain of the emerging human pathogen Candida auris that reacts with MC3 in
      vitro, but which is non-infective in i.v. challenged mice, we demonstrate the
      accuracy of the tracer in diagnosing invasive infections in vivo. This pre
      clinical study demonstrates the principle of using antibody-guided molecular
      imaging for detection of deep organ infections in IC, without the need for
      invasive tissue biopsy.

PMID- 30190719
TI  - Energy Demands of Early Life Drive a Disease Tolerant Phenotype and Dictate
      Outcome in Neonatal Bacterial Sepsis.
AB  - Bacterial sepsis is one of the leading causes of death in newborns. In the face
      of growing antibiotic resistance, it is crucial to understand the pathology
      behind the disease in order to develop effective interventions. Neonatal
      susceptibility to sepsis can no longer be attributed to simple immune immaturity
      in the face of mounting evidence that the neonatal immune system is tightly
      regulated and well controlled. The neonatal immune response is consistent with a
      "disease tolerance" defense strategy (minimizing harm from immunopathology)
      whereas adults tend toward a "disease resistance" strategy (minimizing harm from
      pathogens). One major advantage of disease tolerance is that is less
      energetically demanding than disease resistance, consistent with the energetic
      limitations of early life. Immune effector cells enacting disease resistance
      responses switch to aerobic glycolysis upon TLR stimulation and require steady
      glycolytic flux to maintain the inflammatory phenotype. Rapid and intense
      upregulation of glucose uptake by immune cells necessitates an increased reliance
      on fatty acid metabolism to (a) fuel vital tissue function and (b) produce
      immunoregulatory intermediates which help control the magnitude of inflammation.
      Increasing disease resistance requires more energy: while adults have fat and
      protein stores to catabolize, neonates must reallocate resources away from
      critical growth and development. This understanding of sepsis pathology helps to
      explain many of the differences between neonatal and adult immune responses.
      Taking into account the central role of metabolism in the host response to
      infection and the severe metabolic demands of early life, it emerges that the
      striking clinical susceptibility to bacterial infection of the newborn is at its
      core a problem of metabolism. The evidence supporting this novel hypothesis,
      which has profound implications for interventions, is presented in this review.

PMID- 30190718
TI  - Spontaneous Proliferation of CD4+ T Cells in RAG-Deficient Hosts Promotes Antigen
      Independent but IL-2-Dependent Strong Proliferative Response of Naive CD8+ T
      Cells.
AB  - The fast and intense proliferative responses have been well documented for naive
      T cells adoptively transferred into chronic lymphopenic hosts. This response
      known as spontaneous proliferation (SP), unlike antigen-independent lymphopenia
      induced proliferation (LIP), is driven in a manner dependent on antigens derived
      from commensal microbiota. However, the precise nature of the SP response and its
      impact on homeostasis and function for T cells rapidly responding under this
      lymphopenic condition are still unclear. Here we demonstrate that, when naive T
      cells were adoptively transferred into specific pathogen-free (SPF) but not germ
      free (GF) RAG-/- hosts, the SP response of these cells substantially affects the
      intensity and tempo of the responding T cells undergoing LIP. Therefore, the
      resulting response of these cells in SPF RAG-/- hosts was faster and stronger
      than the typical LIP response observed in irradiated B6 hosts. Although the
      intensity and tempo of such augmented LIP in SPF RAG-/- hosts were analogous to
      those of antigen-dependent SP, the former was independent of antigenic
      stimulation but most importantly, dependent on IL-2. Similar observations were
      also apparent in other acute lymphopenic settings where antigen-dependent T cell
      activation can strongly occur and induce sufficient levels of IL-2 production.
      Consequently, the resulting T cells undergoing IL-2-driven strong proliferative
      responses showed the ability to differentiate into functional effector and memory
      cells that can control infectious pathogens. These findings therefore reveal
      previously unappreciated role of IL-2 in driving the intense form of T cell
      proliferative responses in chronic lymphopenic hosts.

PMID- 30190720
TI  - Recent Developments in Recombinant Protein-Based Dengue Vaccines.
AB  - Recombinant proteins are gaining enormous importance these days due to their wide
      application as biopharmaceutical products and proven safety record. Various
      recombinant proteins of therapeutic and prophylactic importance have been
      successfully produced in microbial and higher expression host systems. Since
      there is no specific antiviral therapy available against dengue, the prevention
      by vaccination is the mainstay in reducing the disease burden. Therefore,
      efficacious vaccines are needed to control the spread of dengue worldwide. Dengue
      is an emerging viral disease caused by any of dengue virus 1-4 serotypes that
      affects the human population around the globe. Dengue virus is a single stranded
      RNA virus encoding three structural proteins (capsid protein, pre-membrane
      protein, and envelope protein) and seven non-structural proteins (NS1, NS2a,
      NS2b, NS3, NS4a, NS4b, NS5). As the only licensed dengue vaccine (Dengvaxia) is
      unable to confer balanced protection against all the serotypes, therefore various
      approaches for development of dengue vaccines including tetravalent live
      attenuated, inactivated, plasmid DNA, virus-vectored, virus-like particles, and
      recombinant subunit vaccines are being explored. These candidates are at
      different stages of vaccine development and have their own merits and demerits.
      The promising subunit vaccines are mainly based on envelope or its domain and non
      structural proteins of dengue virus. These proteins have been produced in
      different hosts and are being investigated for development of a successful dengue
      vaccine. Novel immunogens have been designed employing various strategies like
      protein engineering and fusion of antigen with various immunostimulatory motif to
      work as self-adjuvant. Moreover, recombinant proteins can be formulated with
      novel adjuvants to enhance the immunogenicity and thus conferring better
      protection to the vaccinees. With the advent of newer and safer host systems,
      these recombinant proteins can be produced in a cost effective manner at large
      scale for vaccine studies. In this review, we summarize recent developments in
      recombinant protein based dengue vaccines that could lead to a good number of
      efficacious vaccine candidates for future human use and ultimately alternative
      dengue vaccine candidates.

PMID- 30190721
TI  - T Cells That Help B Cells in Chronically Inflamed Tissues.
AB  - Chronically inflamed tissues commonly accrue lymphocyte aggregates that
      facilitate local T cell-B cell interactions. These aggregates can range from
      small, loosely arranged lymphocyte clusters to large, organized ectopic lymphoid
      structures. In some cases, ectopic lymphoid structures develop germinal centers
      that house prototypical T follicular helper (Tfh) cells with high expression of
      Bcl6, CXCR5, PD-1, and ICOS. However, in many chronically inflamed tissues, the T
      cells that interact with B cells show substantial differences from Tfh cells in
      their surface phenotypes, migratory capacity, and transcriptional regulation.
      This review discusses observations from multiple diseases and models in which
      tissue-infiltrating T cells produce factors associated with B cell help,
      including IL-21 and the B cell chemoattractant CXCL13, yet vary dramatically in
      their resemblance to Tfh cells. Particular attention is given to the PD-1hi CXCR5
      Bcl6low T peripheral helper (Tph) cell population in rheumatoid arthritis, which
      infiltrates inflamed synovium through expression of chemokine receptors such as
      CCR2 and augments synovial B cell responses via CXCL13 and IL-21. The factors
      that regulate CD4+ T cell production of CXCL13 and IL-21 in these settings are
      also discussed. Understanding the range of T cell populations that can provide
      help to B cells within chronically inflamed tissues is essential to recognize
      these cells in diverse inflammatory conditions and to optimize either broad or
      selective therapeutic targeting of B cell-helper T cells.

PMID- 30190722
TI  - Limited Innovations After More Than 65 Years of Immunoglobulin Replacement
      Therapy: Potential of IgA- and IgM-Enriched Formulations to Prevent Bacterial
      Respiratory Tract Infections.
AB  - Patients with primary immunoglobulin deficiency have lower immunoglobulin levels
      or decreased immunoglobulin function, which makes these patients more susceptible
      to bacterial infection. Most prevalent are the selective IgA deficiencies
      (~1:3,000), followed by common variable immune deficiency (~1:25,000).
      Agammaglobulinemia is less common (~1:400,000) and is characterized by very low
      or no immunoglobulin production resulting in a more severe disease phenotype.
      Therapy for patients with agammaglobulinemia mainly relies on prophylactic
      antibiotics and the use of IgG replacement therapy, which successfully reduces
      the frequency of invasive bacterial infections. Currently used immunoglobulin
      preparations contain only IgG. As a result, concurrent IgA and IgM deficiency
      persist in a large proportion of agammaglobulinemia patients. Especially patients
      with IgM deficiency remain at risk for recurrent infections at mucosal surfaces,
      which includes the respiratory tract. IgA and IgM have multiple functions in the
      protection against bacterial infections at the mucosal surface. Because of their
      multimeric structure, both IgA and IgM are able to agglutinate bacteria
      efficiently. Agglutination allows for entrapment of bacteria in mucus that
      increases clearance from the respiratory tract. IgA is also important for
      blocking bacterial adhesion by interfering with bacterial adhesion receptors. IgM
      in its place is very well capable of activating complement, therefore, it is
      thought to be important in complement-mediated protection at the mucosal surface.
      The purpose of this Mini Review is to highlight the latest advances regarding IgA
      and IgM-enriched immunoglobulin replacement therapy. We describe the different
      IgA- and IgM-enriched IgG formulations, their possible modes of action and
      potential to protect against respiratory tract infections in patients with
      primary immunoglobulin deficiencies.

PMID- 30190723
TI  - Tracking of Host Defenses and Phylogeny During the Radiation of Neotropical Inga
      Feeding Sawflies (Hymenoptera; Argidae).
AB  - Coevolutionary theory has long predicted that the arms race between plants and
      herbivores is a major driver of host selection and diversification. At a local
      scale, plant defenses contribute significantly to the structure of herbivore
      assemblages and the high alpha diversity of plants in tropical rain forests.
      However, the general importance of plant defenses in host associations and
      divergence at regional scales remains unclear. Here, we examine the role of plant
      defensive traits and phylogeny in the evolution of host range and species
      divergence in leaf-feeding sawflies of the family Argidae associated with
      Neotropical trees in the genus Inga throughout the Amazon, the Guiana Shield and
      Panama. Our analyses show that the phylogenies of both the sawfly herbivores and
      their Inga hosts are congruent, and that sawflies radiated at approximately the
      same time, or more recently than their Inga hosts. Analyses controlling for
      phylogenetic effects show that the evolution of host use in the sawflies
      associated with Inga is better correlated with Inga chemistry than with Inga
      phylogeny, suggesting a pattern of delayed host tracking closely tied to host
      chemistry. Finally, phylogenetic analyses show that sister species of Inga
      sawflies are dispersed across the Neotropics, suggesting a role for allopatric
      divergence and vicariance in Inga diversification. These results are consistent
      with the idea that host defensive traits play a key role not only in structuring
      the herbivore assemblages at a single site, but also in the processes shaping
      host association and species divergence at a regional scale.

PMID- 30190725
TI  - Genetic Improvement in South African Livestock: Can Genomics Bridge the Gap
      Between the Developed and Developing Sectors?
AB  - South Africa (SA) holds a unique position on the African continent with a rich
      diversity in terms of available livestock resources, vegetation, climatic regions
      and cultures. The livestock sector has been characterized by a dual system of a
      highly developed commercial sector using modern technology vs. a developing
      sector including emerging and smallholder farmers. Emerging farmers typically aim
      to join the commercial sector, but lag behind with regard to the use of modern
      genetic technologies, while smallholder farmers use traditional practices aimed
      at subsistence. Several factors influence potential application of genomics by
      the livestock industries, which include available research funding, socio
      economic constraints and extension services. State funded Beef and Dairy genomic
      programs have been established with the aim of building reference populations for
      genomic selection with most of the potential beneficiaries in the well-developed
      commercial sector. The structure of the beef, dairy and small stock industries is
      fragmented and the outcomes of selection strategies are not perceived as an
      advantage by the processing industry or the consumer. The indigenous and local
      composites represent approximately 40% of the total beef and sheep populations
      and present valuable genetic resources. Genomic research has mostly provided
      insight on genetic biodiversity of these resources, with limited attention to
      novel phenotypes associated with adaptation or disease tolerance. Genetic
      improvement of livestock through genomic technology needs to address the role of
      adapted breeds in challenging environments, increasing reproductive and growth
      efficiency. National animal recording schemes contributed significantly to
      progress in the developed sector with regard to genetic evaluations and estimated
      breeding values (EBV) as a selection tool over the past three decades. The
      challenge remains on moving the focus to novel traits for increasing efficiency
      and addressing welfare and environmental issues. Genetic research programs are
      required that will be directed to bridge the gap between the elite breeders and
      the developing livestock sector. The aim of this review was to provide a
      perspective on the dichotomy in the South African livestock sector arguing that a
      realistic approach to the use of genomics in beef, dairy and small stock is
      required to ensure sustainable long term genetic progress.

PMID- 30190727
TI  - Pakistan's Performance in Global Impact Factor Race.

PMID- 30190726
TI  - A Perspective of the Cross-Tissue Interplay of Genetics, Epigenetics, and
      Transcriptomics, and Their Relation to Brain Based Phenotypes in Schizophrenia.
AB  - Genetic association studies of psychiatric disorders have provided unprecedented
      insight into disease risk profiles with high confidence. Yet, the next research
      challenge is how to translate this rich information into mechanisms of disease,
      and further help interventions and treatments. Given other comprehensive reviews
      elsewhere, here we want to discuss the research approaches that integrate
      information across various tissue types. Taking schizophrenia as an example, the
      tissues, cells, or organisms being investigated include postmortem brain tissues
      or neurons, peripheral blood and saliva, in vivo brain imaging, and in vitro cell
      lines, particularly human induced pluripotent stem cells (iPSC) and iPSC derived
      neurons. There is a wealth of information on the molecular signatures including
      genetics, epigenetics, and transcriptomics of various tissues, along with
      neuronal phenotypic measurements including neuronal morphometry and function,
      together with brain imaging and other techniques that provide data from various
      spatial temporal points of disease development. Through consistent or
      complementary processes across tissues, such as cross-tissue methylation
      quantitative trait loci (QTL) and expression QTL effects, systemic integration of
      such information holds the promise to put the pieces of puzzle together for a
      more complete view of schizophrenia disease pathogenesis.

PMID- 30190728
TI  - Patterns of Inpatient Admissions during Hajj: Clinical conditions, length of stay
      and patient outcomes at an advanced care centre in Makkah, Saudi Arabia.
AB  - Objectives: This study aimed to describe inpatient clinical conditions at an
      advanced care facility in Saudi Arabia during the annual Hajj pilgrimage and to
      determine factors correlating with length of stay (LOS). Methods: This
      retrospective study was conducted at the King Abdullah Medical City (KAMC),
      Makkah, Saudi Arabia, and included all inpatients admitted during the annual Hajj
      pilgrimage between August and October 2015. Demographic, administrative and
      clinical data were collected from patient charts and analysed. Results: A total
      of 296 inpatients were included in the study, of which the majority were male
      (73.6%) and >=55 years old (77%). Walk-in admissions occurred less frequently
      than referrals (38.9% versus 61.1%). Most patients (41.6%) were admitted during
      the peak Hajj period (the 8-13th days of Dhu al-Hijjah). Acute coronary syndrome
      was the most prevalent provisional diagnosis (65.2%). In terms of outcomes, 89.2%
      of the inpatients were discharged in a stable condition, with 37.5% discharged
      within <=24 hours of admission. However, 39.9% required admission to the
      Intensive Care Unit (ICU). Overall, LOS was significantly associated with various
      factors, including the mode of admission, admission period, admitting department,
      number of comorbidities and ICU admission (P <0.050 each). Conclusion: Most of
      admissions were referrals, and the main Hajj period witnessed the majority of
      admissions. The vast majority of inpatients eventually discharged in a stable
      condition. Determinants of the length of hospital stay were the mode of
      admission, admission period, admitting department, number of comorbidities and
      ICU admission.

PMID- 30190730
TI  - Comparative Effectiveness of Teaching Obstetrics and Gynaecological Procedural
      Skills on Patients versus Models: A randomized trial.
AB  - Objective: To compare the effectiveness of learning procedural skills on patients
      versus mannequins and models. Methods: Seventy four interns from two consecutive
      batches at the Department of Obstetrics and Gynaecolgy Unit-I at Jinnah
      Postgraduate Medical Center Karachi participated in the study between April and
      September 2014. Five basic skills; taking a cervical (Pap) smear, intrauterine
      contraceptive device insertion, manual vacuum aspiration, making/ suturing an
      episiotomy and active management of the third stage of labour were identified.
      Interns were randomly allocated to two training groups (Group-1 and 2 of thirty
      eight and thirty six trainees respectively), with Group-I received training on
      the five procedural skills on models and mannequins for four weeks while Group-II
      trained on patients initially. After an evaluation at four weeks the groups
      crossed over with a final evaluation at eight weeks. The evaluation was through
      identical objective structured assessment of technical skills on models and
      mannequins for both groups with standard checklists. Results: There was no
      significant difference in skills between the two groups at the four weeks
      assessment. However at the end of training, Group-1 trainees performed
      significantly better than Group 2 with higher overall tests scores (86.7 +/- 2.7
      versus 80.4 +/- 4.8, p< 0.001). This difference was more marked in skills of
      intrauterine contraceptive device insertion, making and suturing an episiotomy
      and active management of third stage of labour. Conclusion: Our findings suggest
      that simulations using models and mannequins for developing procedural skills can
      be readily incorporated in training programs with potential benefits for teaching
      infrequently performed or more difficult procedures. Our data suggest potential
      benefits of initiation of trainings on simulations and mannequins followed by
      human subject exposure.

PMID- 30190729
TI  - The Efficacy of Laser Doppler Flowmetry, Electric Pulp Test and Cold Test in
      Diagnosing Revascularization of Extrusively Luxated Immature Maxillary Incisors.
AB  - Objective: To evaluate the effect of extrusion on immature permanent tooth PBF
      values during a 6-month post-trauma period and to compare the accuracy of cold
      tests on pulp sensibility of traumatized teeth with that of electric pulp tests
      (EPT). Methods: The study group comprised of 26 extruded immature maxillary
      incisors in 25 trauma patients. The respective contralateral homologous teeth
      (n=25) were included as a positive control group. Teeth in the study group were
      treated by repositioning and splinting. Pulp vitality readings for traumatized
      and control teeth were taken with LDF, EPT and cold test on the day of splint
      removal (2-3 weeks after trauma-T1) as well as 6 weeks (T2), 3 months (T3) and 6
      months (T4) post-trauma. Student t and Mann-Whitney U-tests were used to compare
      data among groups. Statistical significance was set at P< 0.05. Results: LDF gave
      positive vitality readings (>4.5 PU) in all patients from T1 to T4 (with the
      exception of 1 patient at T1). Conclusions: LDF was able to accurately identify
      vitality in traumatized immature teeth even during the first few weeks following
      trauma, whereas conventional sensibility tests were unable to accurately
      recognize vitality shortly after trauma.

PMID- 30190724
TI  - Biomarkers of Cellular Senescence and Skin Aging.
AB  - Cellular senescence is an irreversible growth arrest that occurs as a result of
      different damaging stimuli, including DNA damage, telomere shortening and
      dysfunction or oncogenic stress. Senescent cells exert a pleotropic effect on
      development, tissue aging and regeneration, inflammation, wound healing and tumor
      suppression. Strategies to remove senescent cells from aging tissues or
      preneoplastic lesions can delay tissue dysfunction and lead to increased
      healthspan. However, a significant hurdle in the aging field has been the
      identification of a universal biomarker that facilitates the unequivocal
      detection and quantification of senescent cell types in vitro and in vivo.
      Mammalian skin is the largest organ of the human body and consists of different
      cell types and compartments. Skin provides a physical barrier against harmful
      microbes, toxins, and protects us from ultraviolet radiation. Increasing evidence
      suggests that senescent cells accumulate in chronologically aged and photoaged
      skin; and may contribute to age-related skin changes and pathologies. Here, we
      highlight current biomarkers to detect senescent cells and review their utility
      in the context of skin aging. In particular, we discuss the efficacy of
      biomarkers to detect senescence within different skin compartments and cell
      types, and how they may contribute to myriad manifestations of skin aging and age
      related skin pathologies.

PMID- 30190732
TI  - An approach for developing integrated undergraduate medical curriculum.
AB  - Background and Objectives: Medical schools are to develop integrated medical
      curricula because the term 'integrated curriculum' has grown up and flourished
      globally and it has become mandatory to align the medical education with the
      global concept in Pakistan. This paper aims to present a guideline to design an
      undergraduate integrated medical curriculum. Methods: Various themes are used to
      develop integrated curriculum which are basic medical science, simulation skills,
      clinical science, personality development, research, entrepreneurship and pre
      specialization. Each theme is subdivided, termed a module and its contents
      primarily focus on particular aspect. Results: Knowledge, skill and attitude,
      embodied in themes or modules, are planted in specific way that they have
      horizontal as well as vertical integration. There is no boundary of various
      traditional disciplines in template of five years curriculum. For example,
      diagnosis is a theme which carries contents from medicine, surgery, orthopedics
      etc. Conclusion: The blueprint introduced in this paper would help medical
      educators to draft integrated medical curricula for those institutions which
      intend to switch their medical programs from traditional to integrated one.

PMID- 30190731
TI  - Effects of epidural anesthesia combined with inhalation anesthesia or intravenous
      anesthesia on intrapulmonary shunt and oxygenation in patients undergoing long
      term single lung ventilation.
AB  - Objective: To investigate the effect of epidural anesthesia combined with
      inhalation or intravenous anesthesia on intrapulmonary shunt and oxygenation in
      patients undergoing long term single lung ventilation. Methods: Eighty patients,
      aged 35-75, American Society of Anesthesiology (ASA) classification of I-III,
      undergoing thoracic surgery with one lung ventilation more than three hour, were
      randomly divided into propofol group (group Pro), propofol combined with epidural
      anesthesia group (group Pro+Epi), isoflurane group (group Iso) and isoflurane
      combined with epidural anesthesia group (group Iso+ Epi), 20 patients in each
      group. Arterial blood and mixed venous blood were taken for blood gas analysis,
      and hemodynamic data were recorded at following time points: before induction in
      supine position (T1), 30min after bilateral lung ventilation (T2), 15min after
      one lung ventilation (T3), 30min after one lung ventilation (T4), 60min after one
      lung ventilation (T5), 180min after one lung ventilation (T6), intrapulmonary
      shunt (Qs/Qt) was calculated according to the correlation formula. Results: Qs/Qt
      values at T2-6 in four groups were significantly higher than that of T1, and
      Qs/Qt values at T3-6 was significantly higher than that of T2 (P< 0.05); PaO2 at
      T2-6 were significantly higher than that of T1, with PaO2 at T3-6 were
      significantly lower than T2 (P< 0.05). Between groups, Qs/Qt values in group Iso
      were significantly higher than that of group Pro, Pro+Epi and Iso+Epi at T3-5 (P<
      0.05). There was no significant difference in PaO2 between groups (P> 0.05). CI
      at T3-6 in group Iso and Iso+Epi were significantly higher than that of T1
      (P<0.05), and were significantly higher than that of propofol group (P<0.05). MAP
      at T3-6 in group Pro+Epi and Iso+Epi were significantly lower than that at T1 (P
      <0.05). Heart rate at T4-6 in group Iso were significantly higher than T1, and
      higher than group Pro and group Iso+Epi (P <0.05). Conclusion: One lung
      ventilation may predispose to increase of intrapulmonary shunt and decrease in
      arterial partial pressure of oxygen; isoflurane inhalation anesthesia is more
      likely to cause intrapulmonary shunt, but no changes in arterial partial pressure
      of oxygen.

PMID- 30190733
TI  - Socio-economic factors affecting quality of life of Hemodialysis patients and its
      effects on mortality.
AB  - Objective: Many factors affect quality of life (QOL) of dialysis patients. This
      study was conducted to determine the effect of socio-economic factors effecting
      QOL of hemodialysis patients. Methods: This descriptive multi-centric, follow up
      study was conducted at Department of Nephrology, Mayo Hospital, Lahore, from
      February 2015 to August 2017. All patients who were on regular maintenance
      hemodialysis (MHD) for more than three months and able to read and understand
      Urdu version of Kidney Disease Quality Of Life (KDQOL) tool were included in the
      study. Patients were included from hemodialysis units of Mayo Hospital (MH),
      Shalamar Hospital (SH), and Shaikh Zayed hospital (SZH), Lahore. Patients with
      less than three-month duration on dialysis, with cognitive impairment, dementia,
      active psychosis, non-Urdu readers/speakers were excluded. Demographic data and
      lab data was collected on predesigned pro forma. Patients were divided into
      different groups on the basis of education, monthly income, source of funding for
      treatment and employment. Patients were followed up for two years to determine
      the effect of QOL on mortality. Results: One hundred and thirty-five patients
      were included in the study. Socio-economic factors like education, employment,
      income, funding was compared with KDQOL sub scales and were found statistically
      significant (p-value (<0.05). We found that patients with higher income had
      better work status (p=0.039) but social (0.04) and sexual function (p=0.029) were
      relatively better in patients with low income. Employed patients had better work
      status (p=0.01), ability to do social function (p=0.027) but they had more pain
      (0.049), symptoms/problems of disease (p=0.05) and effect of kidney disease
      (p=0.015). Those patients whose dialysis were funded by their family could
      socially interact (p=0.012) better and deal more efficiently with effect of
      kidney disease (p=0.007). Higher education was associated with better emotional
      well being (p=0.045), patient satisfaction (p=0.046) and staff encouragement
      (p=0.045) then patient with lower level of education. QOL had no effect on
      mortality. Conclusion: The socio-economic factors consisting of education,
      employment, income and funding are important parameters affecting QOL of kidney
      patients. QOL does not affect mortality of the dialysis patients.

PMID- 30190734
TI  - Evaluation of Intraocular pressure, Corneal thickness, and Retinal nerve fiber
      layer thickness in patients with Obstructive Sleep Apnea Syndrome.
AB  - Objective: To evaluate the intraocular pressure (IOP), central corneal thickness
      (CCT), and peripapillary retinal nerve fiber layer (RNFL) thickness in Patients
      with Obstructive Sleep Apnea Syndrome. Methods: In this prospective study, 103
      patients with OSAS (study group) and 37 healthy subjects were enrolled. All
      participants underwent comprehensive ophthalmic examinations. Mean outcome
      measures were intraocular pressure by Goldmann applanation tonometry, CCT
      measurement using ultrasound pachymeter and peripapillary RNFL thickness measured
      by spectral-domain optical coherence tomography. Results: The differences between
      the mean values of RNFL thickness in all quadrants were similar in both groups
      and were not statistically significant (p=0.274). The IOP and CCT measurement
      averages of all patients with OSAS were lower than the control group. However,
      this difference was not statistically significant. There was no correlation
      between the apnea-hypopnea index, lowest oxygen saturation (LAST) or Body Mass
      Index (BMI) and the peripapillary RNFL thickness, IOP or CCT when OSAS group was
      divided by severity. Conclusions: The study results suggest that peripapillary
      RNFL thickness, IOP or CCT did not differ significantly between OSAS and control
      groups. We also found no correlation between apnea severity (AHI), lowest oxygen
      saturation (LAST) and BMI and RNFL, CCT and IOP.

PMID- 30190735
TI  - Comparison of neonatal outcomes between category-1 and non-category-1 Primary
      Emergency Cesarean Section: A retrospective record review in a tertiary care
      hospital.
AB  - Objective: To compare neonatal outcomes between Category-1 and Non-Category-1
      Primary Emergency Cesarean Section. Methods: This was a retrospective analysis,
      conducted at Aga Khan University Hospital Karachi from January 1st 2016 till
      December 31st 2016. Non-probability purposive sampling technique was used. A
      sample size of 375 patients who had primary Emergency Caesarean Section (Em-CS)
      was identified by keeping CS rate of 41.5% and 5% bond on error. Data was
      collected from labor ward, operating theatre and neonatal ward records by using
      structured questionnaire. Results: In the current study, out of 375 participants
      who underwent primary Em-CS; majority (89.3%) were booked cases. Two-hundred
      eighty-two (75.2%) were primiparous women. Two hundred and thirty (61.3%) were at
      term and 145(38.7%) were preterm. The main indication among Category-1 CS was
      fetal distress (15.7%). For Non-Category-1 CS, non-progress of labour (45.1%) was
      the leading cause of abdominal delivery. Except for APGAR score at one minute (p
      value = 0.048), no other variables were statistically significant when neonatal
      outcomes were compared among Category-1 and Non-Category-1 CS. Conclusion: In
      this study, fetal distress and non-progress of labor were the main indications
      for Category-1 and Non-Category-1 CS respectively. We did not find statistically
      significant association between indications of Em CS and neonatal outcomes.
      However further prospective studies are required to confirm this association.

PMID- 30190736
TI  - Analysis of the occurrence of deep venous thrombosis in lower extremity
      fractures: A clinical study.
AB  - Objective: To clarify if fracture site is correlated to the occurrence of deep
      venous thrombosis, and determine the risk factors of deep venous thrombosis in
      lower extremity fractures, help surgeons make prophylaxis for the disease
      correctly. Methods: The patients with lower extremity fractures treated
      surgically in the orthopedics department of our hospital from May 2012 to July
      2017 were reviewed retrospectively. The clinical data including age, gender,
      fracture site, surgery modality, hospital stay, operation time, occupation type,
      hypertension, coronary heart disease, diabetes, smoking status, drinking status,
      postoperative exercises were collected and analyzed. Results: Eight hundred and
      twenty-nine patients were included for analysis, in which 68 were included in
      deep venous thrombosis group, 761 were included in the non-deep venous thrombosis
      group, and the incidence of deep venous thrombosis was 8.2%. There were
      significant differences in age, fracture site, surgery modality, occupation type,
      operation time, smoking status, hospital stay and postoperative exercises between
      the two groups (p<0.05), but no significant differences in gender, drinking
      status, coronary heart disease, diabetes and hypertension (p>0.05). In
      multivariate analysis, old age greater than 50 years, arthroplasty and operation
      time more than three hours were independent risk factors, while physical labor
      and postoperative exercises were protective factors for deep venous thrombosis in
      lower extremity fractures. Conclusion: Fracture site was correlated to the
      incidence of deep venous thrombosis, old age, longer operation time, and
      arthroplasty were independent risk factors, physical labor and postoperative
      exercises were protective factors for deep venous thrombosis in patients with
      lower extremity fractures.

PMID- 30190737
TI  - Radiation safety behavior model for the radiological science departments of
      Universities in Korea.
AB  - Objectives: This study was to employ the major variables relating to radiation
      safety that were derived using the Haddon Matrix to develop a radiation safety
      behavior model based on social cognitive theory that can be applied to improve
      the radiation safety behaviors of professors and students in radiological science
      departments. Methods: The safety levels of students and professor in radiological
      science departments were analyzed in order to design a radiation safety behavior
      management model based on the Haddon Matrix and social cognitive theory, which
      can be used to enhance radiation safety strategically. The survey was
      administered on April 23, 2015, to professor and students of 45 universities
      around South Korea with established radiological science departments, and the
      investigation lasted for 30 days. Results: When multiple linear regression
      analysis was conducted taking the radiation safety behaviors of the students in
      the radiological science departments as the dependent variables, it was found
      that these behaviors were affected by self-efficacy, knowledge of the materials,
      and attitudes towards the materials, in order of greatest to least influence.
      Conclusion: Since the general view on radiation safety management in universities
      is also changing to a maximalist attitude, the level of safety management must be
      increased accordingly.

PMID- 30190738
TI  - Association of serum liver enzyme Alanine Aminotransferase (ALT) in patients with
      type 2 diabetes.
AB  - Objectives: To assess the association of raised serum liver enzyme (ALT) with
      type 2 diabetic subjects. Methods: This retrospective data was accessed at Baqai
      Institute of Diabetology and Endocrinology (BIDE) from January 2005 to May 2016.
      A total of 1966 subjects with type 2 diabetes were included in the study.
      Subjects were divided into two groups; in group A 1284 subjects had ALT within
      the normal range (ALT<=35iu/l) and in Group-B 682 subjects had elevated ALT
      (ALT>35iu/l). Details of demographics, anthropometric measurements and
      biochemical results at baseline were extracted from the health management system
      of BIDE. Data analysis was conducted on Statistical Package for Social Sciences
      (SPSS) version 20. Results: Out of 1966 type 2 diabetic subjects 1284(65.4%) were
      observed with normal value of ALT (<=35) and 682(34.6%) with elevated ALT (>35).
      Overall mean age of subjects was 54.66+/-10.98 years and mean BMI was 27.34+/
      5.99 kg/m2. Significant difference was observed between the groups in age (if
      ALT>35), gender (more likely to be male) and triglyceride (higher if
      ALT>35).Whereas no significant difference was found between the groups in HbA1c,
      cholesterol, HDL and LDL. Conclusion: High frequency of elevated ALT suggests the
      association of liver disease with type 2 diabetes. The type 2 diabetic subjects
      need to be routinely screened and further studies to assess the possible
      associations with NAFLD and insulin resistance are required to further clarify
      the disease process.

PMID- 30190739
TI  - The Role of Nerve Growth Factor (NGF) and Glial Cell Line-Derived Neurotrophic
      Factor (GDNF) in Tic Disorders.
AB  - Objectives: Tic disorders are associated with neurodevelopmental origin, changes
      in dopaminergic neurons, and the formation of immunoreactivity, it is thought
      that neurotrophic factors may be crucial in the emergence of tic disorders. In
      this study, we targeted to explore role of neurotrophic factors in tic disorders.
      The aim of this study was to investigate serum Glial Cell Line-Derived
      Neurotrophic Factor (GDNF) and Nerve Growth Factor (NGF) levels in patients with
      tic disorder and healthy controls. Methods: Thirty-four children, constituted the
      case group, were diagnosed with tic disorder. The control group included 34
      healthy children. Development and Well-Being Assessment (DAWBA) (structured
      interview) and Yale Global Tic Severity Rating Scale (YGTSRS) was applied to the
      patients. NGF and GDNF levels were measured with ELISA kit. Results: In case
      group, serum NGF and GDNF levels were found to be significantly higher in females
      than males (p = 0.042, p = 0.031). It was determined that serum NGF and GDNF
      levels were correlated with each other (r = 0.803, p <0.001) and there were no
      correlations between other parameters. There was no significant difference in NGF
      and GDNF in patients with tic disorder, compared to healthy controls.
      Conclusions: The absence of this relationship does not exclude the hypothesis
      that neurotrophic factors may play a role in the etiopathogenesis of tic
      disorders.

PMID- 30190740
TI  - Efficacy of Vitamin D supplementation in achieving an early Sputum Conversion in
      Smear positive Pulmonary Tuberculosis.
AB  - Objective: To determine the efficacy of Vitamin D supplementation in achieving an
      early sputum conversion in vitamin D deficient smear positive pulmonary
      tuberculosis patients. Methods: This randomized clinical trial was done at Mayo
      hospital Lahore from November 2015 to August 2016. One hundred twenty patients
      with sputum smear positive pulmonary tuberculosis were selected and randomized to
      Group-A (taking anti-tuberculous therapy (ATT) only) and Group-B (taking ATT with
      Vitamin D supplementation). Four doses of100,000 IU of Vitamin D injection
      intramuscularly were given after every 14 days during intensive-phase. Sputum
      examination was repeated at 2nd, 4th, 6th, 8th, 10th and 12th weeks. Efficacy of
      treatment in terms of early sputum conversion between both groups was tested
      using Chi square and independent sample t-test was applied to compare mean values
      of serum vitamin D before and after treatment. P-value <= 0.05 was considered as
      significant. Results: The mean age of patients was 37.18+/-6.81 years in Group-A
      and 39.02+/-7.56 years in Group-B. There were 63 (52.50%) males and 57 (47.50%)
      females. The mean serum Vitamin D was 17.07+/-1.44 in Group-A and 17.23+/-2.37 in
      Group-B at baseline and at 12th week, the levels were 21.77+/-2.23 in Group-A and
      29.24+/-0.72 in Group-B. In Group-A, 7 (11.7%) patients showed positive sputum
      examination and in Group-B, only one (1.7%) patient had positive sputum
      examination at 12th week. The difference was statistically significant (p-value=
      0.028). Conclusion: Four doses of intramuscular vitamin D given after every 14
      days corrected vitamin D deficiency and improved the rate of sputum smear
      conversion in patients of pulmonary tuberculosis.

PMID- 30190741
TI  - Levels of Plasma N-terminal Pro-brain Natriuretic Peptide and D-dimer on the
      Prognosis of Patients with Acute Cerebral Infarction.
AB  - Objective: To investigate the effects of levels of D-dimer and N-terminal pro
      brain natriuretic peptide (NT-pro BNP) on the prognosis of patients with acute
      cerebral infarction. Methods: One hundred and twenty-four patients with acute
      cerebral infarction who were admitted to the hospital between July 2014 and July
      2016 were selected as the observation group; 100 normal people who had health
      examination in the center of physical examination of our hospital were selected
      as the control group. The levels of D-dimer and NT-pro BNP of the two groups were
      observed; the correlation between the levels of plasma NT-pro BNP and D-dimer and
      area of cerebral infarction, complications and death condition of the observation
      group was investigated. Results: The levels of D-dimer and NT-pro BNP of the
      observation group were much higher than those of the control group, and the
      difference was statistically significant (P<0.05). The levels of D-dimer and NT
      pro BNP of the observation group were significantly higher than those of the
      control group, and the difference had statistical significance (P<0.05). The
      levels of plasma NT-pro BNP and D-dimer of the patients with disturbance of
      consciousness and high blood pressure were apparently higher than those with no
      disturbance of consciousness and normal blood pressure, and there was a
      statistically significant difference (P<0.05). The patients were followed up for
      half a year. The levels of D-dimer and NT-pro BNP of the dead patients were much
      higher than those of the survived patients on admission. Conclusion: The levels
      of plasma NT-pro BNP and D-dimer can reflect the disease condition and prognosis
      of patients with acute cerebral infarction. Higher levels of NT-pro BNP and D
      dimer indicates poorer prognosis. This work can provide a guidance for the
      clinical treatment of acute cerebral infarction.

PMID- 30190742
TI  - Occurrence of traumatic dental injuries among preschool children with Autism
      Spectrum Disorder.
AB  - Objective: To determine the occurrence of traumatic dental injuries (TDIs) among
      Saudi preschool children with autism spectrum disorder (ASD) and compare it with
      Saudi preschool children without ASD. Methods: This study was conducted on a
      randomly selected sample of three to five year old Saudi preschool children in
      Riyadh, Saudi Arabia. The sample consisted of two groups; a study group (SG) of
      257 ASD children, and a control group (CG) of age- and gender-matched 257
      children without ASD. Clinical examinations were performed at selected ASD
      centers and kindergartens to determine the occurrence of TDIs based on modified
      World Health Organization (WHO) classification system. Results: Out of 514
      children examined, 108 (21.0%) had suffered TDIs. The prevalence of TDIs was
      significantly higher in the SG (25.7%) children than the CG (16.3%) [p=0.012].
      The primary maxillary central incisors were the most commonly affected teeth in
      both the groups; significantly more in CG (72.9%) than SG (50.1%) [p=0.017].
      Enamel fracture was the most frequent type of TDI in both the groups;
      significantly more in CG (29.2%) than SG (21.1%) [p=0.032]. Luxation injuries and
      tooth avulsions were significantly higher in the SG than the CG (p=0.028).
      Conclusions: The occurrence of TDIs was higher in Saudi preschool children with
      ASD than in non-ASD children.

PMID- 30190743
TI  - Roles of medical education department: What are expectations of the faculty?
AB  - Background & Objective: Pakistan like many Asian countries is investing in
      medical education to address increased societal needs and to meet the requirement
      of national and international accrediting bodies. Establishing medical education
      departments is part of this investment. The research question was "What are the
      expectations of faculty from medical education department?" The objective of this
      study was to explore the Faculty's perception about the roles of medical
      education department and their suggestions for its future endeavors. Methods: A
      qualitative case study design was chosen for this study. Heterogeneous group of
      faculty members from basic and clinical sciences departments of University
      College of Medicine, Lahore were invited for this study. They represented a
      variety of disciplines, and seniority levels. They were queried about their
      perception of the roles of medical education department and were encouraged to
      give suggestions for better functioning of department. Data was collected by
      audio recording through focus group interviews. Data analysis was done using
      NVIVO 11 software. Results: Initially 55 nodes/codes emerged which were then
      condensed to 35 nodes. Out of these three main themes emerged. The three emergent
      themes were: Knowledge about the roles of medical education
      department.Interactions with the medical education department.Future Prospects of
      the medical education department. Roles of medical education department
      identified by the faculty were mainly related to faculty development, curriculum
      planning and implementation, student support, policy making for student
      induction, improving teaching strategies, student assessment, quality assurance
      and accreditation of the medical college. Faculty development not only
      encompassed faculty training but also provision of opportunities for research and
      curriculum development. Student support was found to be a neglected role and
      faculty members suggested it to be an important area to be looked upon by medical
      education departments. Conclusion: Institutions must ensure consultation with
      faculty members and should take proactive measures to sustain change, including
      giving ownership and team building among the faculty members.

PMID- 30190745
TI  - Are there any preventable risk factors for women who had surgery for Pelvic Organ
      Prolapse and stress Urinary Incontinence?
AB  - Objective: The present study evaluates the preventable risk factors in
      symptomatic women with previous surgery for pelvic organ prolapse (POP) and/or
      stress urinary incontinence (SUI). Methods: Four hundred and one women previously
      operated were divided into two groups as; women operated for POP (325 cases) and
      women operated for SUI (76 cases). The control group consisted of 233 age and
      body mass index (BMI)-matched subject operated for benign gynecologic reasons and
      exhibited no evidence of POP or SUI. These groups were compared in terms of age,
      BMI, gravida, parity, mode of delivery, smoking status, menopause status and
      chronic diseases. Results: Grand_multiparity (parity >=5) increased the risk of
      POP/SUI surgery and POP surgery 2.71 and 2.94 times, respectively (p=0.0003 and
      p=0.0001, respectively). Vaginal birth increased the risk of POP/SUI surgery 2.33
      times (p=0.03). Conclusion: Grand_multiparity increased the risk of POP/SUI
      surgery and POP surgery while vaginal birth increased the risk of POP/SUI
      surgery. Among them, particularly, grand_multiparity seem to be the only
      preventable risk factors.

PMID- 30190744
TI  - Evaluation of serum biomarkers for detection of preeclampsia severity in pregnant
      women.
AB  - Objectives: To determine serum biomarkers in detection of preeclampsia severity
      among pregnant women. Methods: Among 450 pregnant women with various severity of
      preeclampsia, serum biomarkers ofaspartate aminotransferase (AST), alanine
      aminotransferase (ALT), lactate dehydrogenase (LDH), hemoglobin (Hb), platelet
      count (PLT), uric acid, direct bilirubin, total bilirubin, creatinine, and
      alkaline phosphatase were compared using area under the Receiver operating
      characteristic (ROC) curve and Area Under the Curve (AUC). Results: The mean age
      of women was 30.63+/-6.43 years and with mean gestational age of 34.69+/-3.97
      weeks. The mean level of LDH, ALT, uric acid, and creatinine were significantly
      higher in the women with severe type of preeclampsia compared to those with mild
      type. LDH level had ROC and AUC of more than 0.80, with highest sensitivity, and
      moderatespecificityin comparison to other markers. Conclusion: Biomarkers such as
      ALT, uric acid, and LDH were shown to be prognostic in detection of theseverity
      of preeclampsia. LDH was demonstrated to significantly be a better prognostic
      test in detection of preeclampsia severity.

PMID- 30190746
TI  - Exercise therapy versus surgery for lumbar spinal stenosis: A systematic review
      and meta-analysis.
AB  - Objective: To compare the effectiveness of exercise therapy with surgery for
      lumbar spinal stenosis. Methods: Five English databases PubMed, the Cochrane
      Library, Web of science, OVID and PEDro database were searched for randomized
      controlled trials comparing surgical procedures with exercise therapy for lumbar
      spinal stenosis. Information on patients, study design, inclusion criteria,
      intervention and follow-up, outcomes, treatment details and adverse events were
      extracted. Meta-analysis was performed using Review Manager Version 5.3. Results:
      Two randomized controlled trials and one mixed design trial with a total of 897
      patients were included. The pooled results showed a significant difference
      between exercise and surgery in Oswestry Disability Index at two years (MD= 3.85,
      95%CI: 0.48 to 7.22; P=0.03), but no significant difference at six months (MD=
      2.18, 95%CI: -2.80 to 7.17; P=0.39) and one year (MD= 4.26, 95%CI: -1.79 to
      10.32; P=0.17). In terms of physical function of 36 Items Short Form Health
      Survey, there were no significant differences between exercise and surgery at six
      months (MD= -2.23, 95% CI: -7.46 to 2.99; P=0.40), one year (MD= -2.17, 95% CI: 
      7.44 to 3.10; P=0.42) and two years (MD= -0.67, 95% CI: -6.16 to 4.82; P=0.81).
      Conclusion: In brief, the current evidence demonstrated a trend that exercise
      therapy had a similar effect for lumbar spinal stenosis compared with
      decompressive laminectomies. However, for the small sample size and low
      methodology quality of the included trials, some rigorously designed and large
      scaled RCTs need to be performed to confirm the conclusion.

PMID- 30190747
TI  - Protein requirement and its intake in subjects with diabetic foot ulcers at a
      tertiary care hospital.
AB  - Objective: To assess the protein intake and requirement among subject with type 2
      diabetes having foot ulcers. Methods: This study was conducted at Baqai Institute
      of Diabetology & Endocrinology (BIDE), a tertiary care diabetes centre of
      Karachi, Pakistan among people with type 2 diabetic foot ulcer attending foot
      clinic from January 2012 to March 2015. The baseline characteristics, dietary
      intake and laboratory investigations of the study participants were obtained
      through electronic hospital database "Health Management System" (HMS) based on
      the 24 hours dietary recall interview. Total grams of protein were calculated
      from each food group consumed by the subject. Protein intake of the subjects was
      recorded in mean grams and the protein requirement was calculated according to
      their body weight. The comparison of intake and requirement of protein choices
      was done through comparing the mean of both variables. SPSS version 13 was used
      for analysing the results. Results: A total of 542 subjects were included in the
      study, 365 (67.2%) were males and 178 (32.8%) were females. Mena age of the
      subject was 54.61+/-10.51 (yrs) with the duration of diabetes and mean body mass
      index were 14.22+/-7.98 (yrs) and 26.65+/-5.38 (kg/m2), respectively. The dietary
      records showed the protein intake of subjects with diabetic foot ulcer is not
      appropriate when compared to daily requirement. Mean grams of protein intake is
      76.87gms in males and 56.84gms in females. On the other-hand protein requirement
      is much higher than the intake, which is 219.5gms in males and 130.2gms in
      females. Conclusion: Dietary counselling should be a part of the treatment among
      subjects with diabetic foot ulcer to identify their nutritional needs and
      suggesting them better option to fulfil their protein requirement essential for
      wound healing process.

PMID- 30190749
TI  - Comparison of two types of exercises in the treatment of lumbar spinal stenosis.
AB  - Objective: To evaluate the efficacy of core stability exercise versus
      conventional exercise in the treatment of lumbar spinal stenosis. Methods:
      Between January 2014 and May 2017, patients with lumbar spinal stenosis were
      recruited and divided into group of core stability exercise or conventional
      exercise randomly. All the patients were treated using middle frequency
      electrotherapy, in addition to that, the patients in group of core stability
      exercise were treated using core stability exercise. The patients in group of
      conventional exercise were treated using conventional exercise. The outcome was
      evaluated using Japanese Orthopedic Association (JOA) score, self-reported
      walking capacity and lumbar lordosis angle at baseline and after treatment.
      Results: In the current study, sixty-two patients with lumbar spinal stenosis met
      the inclusion and exclusion criteria, in which 33 patients were included in group
      of core stability exercise and 29 in group of conventional exercise. After
      treatment, both Japanese Orthopedic Association scores (p<0.05) and self-reported
      walking capacity (p<0.05) increased significantly in each group when compared
      with baseline. The self-reported walking capacity and JOA scores in the group of
      core stability exercise were significantly higher than those in the conventional
      exercise group (p<0.05). However, both the intragroup and intergroup comparison
      of lumbar lordosis presented with no significance (p>0.05). Conclusion: Core
      stability exercise presents with better efficacy than conventional exercise in
      the treatment of lumbar spinal stenosis.

PMID- 30190748
TI  - Effect of intrauterine insemination treatment on sexual function and quality of
      life for infertile women.
AB  - Objectives: To evaluate the effect of intrauterine insemination (IUI) on sexual
      functioning, quality of life and psychological well-being. Methods: One hundred
      and thirty four infertile women going to IUI treatment as study group and 134
      women who do not report any infertility complaint attending to gynecology clinic
      for routine control as control group were enrolled. Demographic data of the
      patients were collected. Patients were asked to complete Female Sexual
      Functioning Index (FSFI), Beck Depression Inventory (BDI) and SF 36 form.
      Results: Total FSFI score (mean+/-SD) for study group was 23.4+/-4.1 and 24.8+/
      3.4 for control group (p<0.05). This means a lower sexual function for patients
      going to IUI. There were also statistically significant differences according to
      subscales of FSFI scores for sexual desire, arousal and satisfaction. Mean+/-SD
      scores for Beck Depression Inventory analysis was 18.6+/-9.8 for study group and
      18.5+/-7.1 for control group. According to SF-36 scores, there were statistically
      significant differences between the groups for four subscales: Role
      physical,bodily pain,general health and vitality. Conclusions: Going to an IUI
      treatment has negative effects on FSFI scores and some of SF 36 scores but we did
      not find a significant negative effect on BDI scores.

PMID- 30190750
TI  - Perceived stress and monetary burden among thalassemia patients and their
      caregivers.
AB  - Objective: To find the perceived stress level and monetary burden in the
      thalassemia patients and their caregivers related to thalassemia treatment
      sessions. Methods: A descriptive cross sectional study was conducted at
      Rawalpindi Thalassemia Centre and Military Hospital Rawalpindi of six months'
      duration from November 2016 to April 2017. A total of 87 sample size was
      calculated by using WHO sample size calculator. Participants were inducted
      through purposive sampling technique from thalassemia centers. A validated
      standardized Cohen's Perceived Stress score was used. Data were entered and
      analyzed in SPSS 22. Results: Mean age of the participants was 30.42 +/- 14.53
      years. There were 30 (34.2%) males and 57 (65.8%) females. There were 39 (51.3%)
      patients and 48 (48.7%) caregivers. The mean income per month of the participants
      was 48706.9 +/- 39492.68 PKR. The mean total expenditure per treatment session
      was 48706 +/- 4037.12 PKR. Among the patients, there were 15 (38.5%) who were
      having average stress, while 4 (10.3%) were having moderate stress while 45
      (51.7%0 were having severe stress. Among the caregivers, 10 (20.8%) were having
      mild stress, 13 (27.1%) were having moderate stress while 25 (52.1%) were having
      severe stress. The stress among the two groups was not statistically significant
      (p=0.066). Conclusion: More than half of the patients and caregivers were having
      a high perceived stress levels and there was a significant association between
      the two groups. The monetary burden was a lot to bear by the patients and the
      cost of treatment session most expensive.

PMID- 30190751
TI  - Anti-Cyclic Citrullinated Peptide Antibody and Periodontal Status in Rheumatoid
      Arthritis Patients.
AB  - Objectives: Studies have shown that periodontal disease and Rheumatoid Arthritis
      (RA) shared similar pathogenesis. Anti-Cyclic Citrullinated Peptide anibodies
      (anti-CCP) has recently been used for diagnosis of RA. Thus, this study aimed to
      assess the levels of anti-CCP antibodies and periodontal status in RA patients.
      Methods: Forty four RA patients were included in this study. The blood samples
      were analysed for anti-CCP levels. Plaque Score (PS), Gingivitis Score (GS),
      Probing Pocket Depth (PPD) and Clinical Attachment Loss (CAL) were recorded for
      assessment of periodontal status. Relevant clinical information was obtained from
      medical records. Results: Mean anti-CCP level was 180.8 +/- 290.3 Unit/ml. The
      results showed that 27.3% patients had poor oral hygiene (PS >60%; mean anti-CCP
      84.22 +/- 167.51 Unit/ml), 52.3% had generalized gingivitis (mean anti-CCP 145.07
      +/- 269.17 Unit/ml), and 20.5% had mean CAL of >3mm (mean anti-CCP 56.81 +/-
      119.02 Unit/ml). None of patients presented with deep PPD > 4mm. The levels of
      anti-CCP showed no significant association with periodontal status (p=0.27).
      Conclusion: Most RA patients were positive for anti-CCP antibodies and presented
      with generalized gingivitis. Oral hygiene education should be reinforced in RA
      patients to prevent further progression of periodontal disease. Nevertheless,
      studies with larger sample size should be carried out to obtain more conclusive
      findings.

PMID- 30190752
TI  - Factors contributing to the lack of interest in research activities among
      postgraduate medical students.
AB  - Objective: To determine the factors contributing to lack of interest in research
      activities among postgraduate residents in pediatric medicine. Methods: This
      cross-sectional survey was conducted at The Children's Hospital Lahore, Pakistan
      in August 2017. The questionnaire was distributed to 105 postgraduate residents
      working in pediatric medicine department and 90 of them returned the completed
      proforma (response rate; 86%). Data was analyzed by SPSS version 22. Results: Out
      of 90 residents' females were predominant (n=58/90; 64.4%). Mean age of the
      participants was 28.22 +/- 2.092 years. Majority were unmarried (n=57; 63.3%).
      The highest mean score (2.31+/-0.697) was regarding "Lack of proper training for
      research", followed by "lack of previous exposure" (2.26+/-0.728) and "over
      loaded curriculum" (2.13+/-0.753). "Uncooperative faculty" and "funding issues"
      as a barrier towards research (p=0.016 and 0.014 respectively) was mentioned by
      males more than females. "Social and family commitment" was a significant
      perceived barrier in married residents as compared to unmarried residents
      (p=0.001). The residents in the younger age group were more reluctant to do
      research due to "over loaded curriculum" (p=0.038). Conclusion: Lack of proper
      training of research, lack of previous exposure and time management are the major
      factors affecting resident's research work, whereas married residents face more
      social/family constraints as compare to unmarried residents.

PMID- 30190753
TI  - Neutrophil-to-lymphocyte ratio and mean platelet volume can be useful markers to
      predict sepsis in children.
AB  - Objectives: Neutrophil-to-Lymphocyte Ratio (NLR) and Mean Platelet Volume (MPV)
      have been found to be useful indexes for the diagnosis of sepsis in adults.
      However, the knowledge of their roles and cut-off values in pediatric patients is
      limited. The primary objective of this study was to assess the ability of NLR and
      MPV to predict sepsis in children. A secondary aim was to evaluate the comparison
      of these parameters with C-reactive Protein (CRP). Methods: The study was
      conducted on pediatric patients, who had two or more of the following criteria
      were included in the study: tachycardia, tachypnea, temperature change,
      leukocytosis, or leukopenia for age. Patients were classified into sepsis and non
      sepsis groups. The sepsis group was defined as the presence of two or more age
      specific Systemic Inflammatory Response Syndrome (SIRS) criteria and increased
      Procalcitonin (PCT) level (>0.5 ng/ml). Result: The median age of the study
      population was 18 (6-169) months. Two hundred-sixty four episodes of sepsis were
      recorded in 125 patients. Eighty two were classified as sepsis and 182 as non
      sepsis. CRP level and MPV value were significantly higher in the sepsis group
      compared to non-sepsis group. The median CRP level was 47.8 mg/dl (10.2-119.5) in
      the sepsis group and 18.6 mg/dl (4.9-66.1) in the non-sepsis group (p=0.006). In
      the sepsis group, the median MPV value was 8.4 (7.6-9.5) and it was 7.8 (7.1-8.5)
      in the non-sepsis group (p=0.001). Significant correlations were found between
      the procalcitonin (PCT) and CRP level (p<0.001; r = 0.279), NLR (p=0.02; r =
      0.186) and MPV (p<0.001; r = 0.243). MPV had the highest specificity for
      predicting sepsis (75.8%). The largest AUC was 0.629 with a cut-off value 8.5 for
      MPV, while the AUC was 0.557 with a cut-off value 1.97 for NLR and 0.606 with a
      cut-off value 38.9 for CRP. Conclusions: NLR and MPV values should alert
      clinicians to the possibility of sepsis and to initiate or change antibiotic
      treatment.

PMID- 30190754
TI  - A comparison of exposure of Glottis using the Airtraq or the Macintosh
      Laryngoscope in Potentially difficult airway management: A self-controlled
      clinical trial.
AB  - Objective: To compare glottis exposure of the same patients with potentially
      difficult tracheal intubation (PDTI) subjected to Airtraq laryngoscopy and
      Macintosh laryngoscopy under consciousness and topical anesthesia. Methods: A
      total of 147 PDTI patients with American Society of Anesthesiologists (ASA) I-III
      were subjected to Airtraq and Macintosh laryngoscopy performed by experienced
      anesthesiologists under consciousness and topical anesthesia. Results: All
      patients were successfully intubated. Among them, three patients were intubated
      with fiberoptic bronchoscopy, 13 with Macintosh laryngoscopy and 131 with Airtraq
      laryngoscopy. Of the patients with Cormack and Lehance (C&L) Grade-I glottic
      view, 88 were subjected to Airtraq laryngoscopy and five to Macintosh
      laryngoscopy; Of the patients with C&L Grade-II glottic view, 56 were subjected
      to Airtraq laryngoscopy and 21 to Macintosh bronchoscopy; Of the patients with
      C&L Grade-III glottic view, three were subjected to Airtraq laryngoscopy and 112
      to Macintosh bronchoscopy; Of the patients with C&L Grade-IV glottic view, none
      was subjected to Airtraq laryngoscopy and 9 to Macintosh laryngoscopy.
      Conclusions: Airtraq laryngoscopy could significantly improve the glottis
      exposure and reduce the difficulty of intubation for patients with potentially
      tracheal intubation compared to the traditional Macintosh laryngoscopy.

PMID- 30190756
TI  - Plasma surfactant protein-A levels in apparently healthy smokers, stable and
      exacerbation COPD patients.
AB  - Objective: To compare the plasma level of surfactant protein-A in apparently
      healthy smokers, stable and exacerbation Chronic Obstructive Pulmonary Disease
      (COPD) patients. Methods: This was a comparative study conducted from January,
      2015 to March, 2016. This study was conducted on 87 subjects of both gender and
      age between 30-70 years. Of the total 87 subjects; 29 subjects were "healthy
      smokers" selected from general population as control group. Another 29 were
      "stable COPD" patients free of exacerbation since last six weeks. Lastly, another
      29 subjects were "exacerbated COPD" patients with 7-10 days of exacerbation. COPD
      was diagnosed on the basis of relevant history and spirometry showing post
      bronchodilator FEV1/FVC <0.70. Surfactant Protein-A level (ng/ml) was estimated
      by a specific solid phase enzyme linked immunosorbent assay (ELISA) using
      automated EIA analyzer. Results: The SP-A levels, determined by competitive
      ELISA, was significantly higher (P<0.025) in healthy smokers (44.19+/-39.17
      ng/ml) and exacerbated (43.86+/-40.17) than the stable COPD (25.89+/-18.85)
      patients. The lung function parameters (FEV1, FVC and FEV1/ FVC) were lower in
      COPD patients compared to healthy smokers and were related to the duration of
      smoking. Conclusion: Current smokers and exacerbated patients had higher values
      of SP-A protein than stable COPD patients since they had stopped smoking.

PMID- 30190755
TI  - Prevalence of depression among adults with sickle cell disease in the southern
      region of Saudi Arabia.
AB  - Objectives: Sickle Cell Disease (SCD) as other chronic medical conditions is
      commonly complicated by psychiatric symptoms. Saudi SCD patients are usually
      originally from Eastern and Southwestern Provinces. The main objective of our
      study was to evaluate the prevalence of depression among adults with SCD in
      southern region of Saudi Arabia. We also studied the sociodemographic profiles
      for these individuals. Methods: We conducted a cross-sectional study among
      subjects (n=78) in Armed Forces Hospital, Southern Saudi Arabia using an Arabic
      version of a Hamilton Rating Scale for Depression HAM-D that has received
      widespread use and have undergone reliability and validity testing. The data were
      analyzed by SPSS 22 package program. Pearson's chi-squared test is used to
      examine the association between the categorical outcome variables A p-value less
      than 0.05 was considered statistically significant. Results: Most of the
      participants were young adults (26.4+/- 9.2 years), single females not working
      who are originally from Jizan and Mahayel Aseer, Southern Saudi Arabia. The
      prevalence of depressive symptoms was 85.9%. When the association between
      depression in SCD patients and different demographic characters was tested, no
      significant relation between depression and any factors was discovered.
      Conclusion: This study confirms that depression is common in adult patients with
      SCD as confirmed by previous studies. On the other hand, socio-demographic
      factors were not significant predictors of depression in SCD patients. Further
      research is needed to explore the magnitude and impact of this problem at the
      national level.

PMID- 30190757
TI  - Evaluation of patients undergoing abdominal sacrocolpopexy due to symptomatic
      pelvic organ prolapse in terms of gastrointestinal complications.
AB  - Objectives: To evaluate the intra- and postoperative gastrointestinal
      complications following abdominal sacrocolpopexy and determine the possible
      causes. Methods: A total of 86 patients who underwent abdominal sacrocolpopexy
      due to symptomatic pelvic organ prolapse between January 2014 and January 2016 at
      Izmir Tepecik Training and Research Hospital Obstetrics and Gynecology Clinic
      were retrospectively reviewed using the hospital information system. Patients
      were divided into two groups: those with and without prolonged length of hospital
      stay. They were evaluated in terms of gastrointestinal complications and risk
      factors. Results: The reason for prolonged hospitalization was nausea and
      vomiting in 24 (88%) of 27 patients. The symptoms in these patients were
      recovered with hydration, stopping of oral intake, and administration of
      antiemetics. Nasogastric decompression and parenteral nutrition were required in
      three (11%) patients due to clinical and radiological evidence of ileus. The
      parameter that significantly prolonged the length of hospital stay was prior
      abdominal surgery (p < 0.05). Conclusion: There were obvious gastrointestinal
      complications in three out of 27 patients with prolonged length of hospital stay.
      These findings may be beneficial for preoperative patient counselling.

PMID- 30190758
TI  - Dynamic changes and clinical significance of serum S100B protein and glial
      fibrillary acidic protein in patients with delayed encephalopathy after acute
      carbon monoxide poisoning.
AB  - Objective: To study the dynamic changes and clinical significance of serum S100B
      protein and glial fibrillary acidic protein (GFAP) in patients with delayed
      encephalopathy after acute carbon monoxide poisoning (DEACMP). Methods: This
      study was conducted among DEACMP patients who were hospitalized from November
      2014 to February 2016. Serum levels of S100B and GFAP in 66 DEACMP patients were
      measured by ELISA. Changes in patient states were examined dynamically using
      activities of daily living (ADL) scale, information-memory-concentration test
      (IMCT) and Hasegawa's dementia scale (HDS), and compared with those of 64
      patients without DE after ACMP. Results: Serum S100B [(0.59 +/- 0.11) ng/ml] and
      GFAP [(227.67 +/- 12.43) ng/ml] levels of DEACMP group in acute phase were
      significantly higher than those of ACMP group [(0.48 +/- 0.10) ng/ml and (178.91
      +/- 11.47) ng/ml] and DEACMP group in recovery phase [(0.49 +/- 0.12) ng/ml and
      (179.54 +/- 12.32) ng/ml] (all P<0.05). Serum S100B and GFAP levels of DEACMP
      group were significantly correlated in both acute and recovery phases (r=0.432 in
      acute phase, P=0.007; r=0.378 in recovery phase, P=0.034). ADL, HDS and IMCT
      scores of DEACMP group in acute phase were (45.12 +/- 3.12), (7.98 +/- 1.02) and
      (9.61 +/- 1.41) points respectively, which were significantly different from
      those of recovery phase [(33.25 +/- 3.09), (16.13 +/- 1.17) and (19.54 +/- 1.43)
      points respectively] (P<0.05). Conclusions: DEACMP was accompanied by secondary
      brain injury, for which glial activation may be important. Serum S100B and GFAP
      levels may be related to prognosis.

PMID- 30190760
TI  - Association between grades of Hydronephrosis and detection of urinary stones by
      ultrasound imaging.
AB  - Objective: To correlate between hydronephrosis grades and detection of urinary
      stones by B-mode ultrasound imaging. Methods: This study included 210 ultrasound
      reports of patients who underwent abdominal ultrasound imaging in the period from
      1st January 2016 to 31st October 2017, and diagnosed as hydronephrosis. Data
      collected from the ultrasound reports. The detection rates of stones using B-mode
      ultrasound imaging compared in different grades of hydronephrosis. Chi-square
      test and Odds Ratio (OR) were performed to assess the relationship between
      variables. Results: Of 210 patients, hydronephrosis was unilateral in 91.8% of
      patients and bilateral in 8.1%. It was distributed in grade 2, grade 3, grade 1
      and grade 4 in 58.57%, 20%, 12.38% and 9.1% of the patients respectively. B-mode
      ultrasound imaging determined the cause of hydronephrosis in 65.2% of cases.
      Urinary stones were the cause in 60% of the patients. The detection rate of
      urinary stones was 50%, 61% and 71.4% for grades 1, 2 and 3 hydronephroses
      respectively. On simple logistic regression analysis, urinary stones detected in
      Grade-3 were four times more compared to that in grade 4 (P=0.016) (OR 4.125, 95%
      CI 1.29-13.136%). Conclusion: Detection of urinary stones as the cause of
      hydronephrosis increases with increasing the grade of hydronephrosis from Grade-I
      to Grade-III and decrease in Grade-IV. Urinary stones were the cause of
      hydronephrosis in 60% of the patients in this study.

PMID- 30190759
TI  - Levels of serum thyroxine, triidothyronine and thyrotropin in patients with acute
      myocardial infarction.
AB  - Objective: To determine the levels of serum thyroxine (T3, T4), triiodothyronine
      and thyrotropin in patients with acute myocardial infarction (AMI). Methods: It
      was an observational prospective study and 60 patients (both males and females)
      of AMI, (diagnosed by ECG & cardiac enzymes.) were included. Serum thyroid
      stimulating hormone (TSH), Free T3 and Free T4 were measured and relevant data
      was entered into a predesigned proforma. Results: FT3 levels were below the
      reference range in 56.7% cases while both the FT4 and TSH values were found to be
      the lower limit of normal range. When the decrease in FT3 was correlated with the
      duration of illness, it was found that significant inverse correlation existed
      between FT3 value and the duration of illness and linear regression line was
      obtained. No such correlation existed between FT4 and TSH values. Conclusion:
      Thyroid hormone levels (FT3) decreases in AMI and this change is associated with
      the duration of illness.

PMID- 30190761
TI  - Evaluation of medication adherence in hypertensive patients and influential
      factors.
AB  - Objective: This study aims to evaluate medication adherence in hypertensive
      patients and to identify the influential factors. Methods: This descriptive,
      cross-sectional study included a total of 147 hypertensive patients who were
      admitted to Akdogan Health Center between December 2016 and February 2017. The
      Descriptive Data Form and Medication Adherence Self-Efficacy Scale were used as
      the data collection tools. Results: The mean Medication Adherence Self-Efficacy
      Scale score was found to be 70.29 +/- 8.52. Age, duration of HT, the frequency of
      follow-up visit for HT, the status of taking medication regularly, the frequency
      of blood pressure measurement and the status of alternative method use were found
      to be effective in medication adherence. Conclusions: Our study results suggest
      that medication adherence is good in patients with hypertension (HT). Factors
      which are effective in medication adherence should be taken into consideration,
      when evaluating the medication adherence in patients with HT.

PMID- 30190762
TI  - Prevalence of Migraine among patients of Depressive Disorder.
AB  - Objective: To find out the prevalence of Migraine among patients of Depressive
      Disorder. Methods: A descriptive cross sectional study, conducted at Department
      of Psychiatry and Behavioral Sciences, JPMC, Karachi from 1st January 2014 to
      30th June 2014. Total 272 patients were enrolled in the study. Depressive
      disorder was diagnosed as per ICD-10 criteria and Migraine headache as ICHD-2
      criteria for diagnosis. Results: A total of 272 patients with mean age of 31.85
      +/- 8.7 were enrolled. Out of 272 cases 64% were females; Out of total cases
      86.4% were married. Migraine with aura was seen among 6.6% and migraine without
      aura was present among 26.1%. Migraine was linked more with females and married
      and of those having severe Depressive disorder. Conclusion: Migraine headache is
      common among depressed people, particularly females and having severe depression,
      so it ought to be remembered that while looking for Depressive disorder or
      headache the other condition must be remembered.

PMID- 30190763
TI  - The effect of facet joint injection on lumbar spinal stenosis with radiculopathy.
AB  - Objectives: Facet Joint Injection (FJI) is known to be effective in axial back
      pain, but the purpose of this study was to assess the effects of FJI on patients
      treated with it among those with Lumbar Spinal Stenosis (LSS). Methods: We
      conducted a retrospective database analysis and investigated electronic medical
      records of 125 LSS patients treated with FJI in the pain clinic of Chungbuk
      National University Hospital from November 2, 2016 to July 31, 2017. Sex, age,
      histories of low back surgery, complaining of neurogenic claudication,
      symptomatic sites of patients, FJI sites, number of sites of FJI, triamcinolone
      dosage, Numeric Rating Scale (NRS) before and after treatment, facet joint
      capsule rupture during treatment, and improvement of neurogenic claudication
      after treatment, were examined. Results: Among 125 patients, we investigated 91
      patients who met the criteria. There was significant difference in NRS before and
      after treatment (p<0.000). Forty one patients with reduction of NRS more than 30%
      after FJI were allocated to effect group. FJI was more effective in patients who
      did not have the surgery (p=0.044), as well as those who showed an improved
      neurogenic claudication after treatment (p=0.001). Other measured values did not
      show statistical significances. Conclusions: FJI has relatively a lower risk and
      is simpler in terms of techniques than other interventional treatments performed
      within the spinal canal. Therefore, FJI may be another interventional treatment
      option in patients with pain by LSS. In the future, studies for FJI indication in
      LSS patients should be additionally required.

PMID- 30190764
TI  - Treatment results of small bowel perforations due to unusual causes.
AB  - Objectives: Although non-traumatic Small Bowel Perforations (SBPs) are rare, they
      have high rates of morbidity and mortality in case of late presentation.
      Aetiological factors vary across different geographical regions. In this paper,
      SBPs caused by anything other than trauma and other well-known causes are
      presented and the current literature is reviewed. Methods: The study was
      conducted at General Surgery Clinics of two different tertiary university
      hospitals between January 2008 and September 2016. The authors directly involved
      in managing the patients. This study was approved by the ethical institutional
      board and was performed at the Department of General Surgery, School of Medicine,
      Sakarya University. The medical records of patients retained in both hospitals
      are electronic. Medical records of subjects who had undergone emergency
      operations with a prediagnosis of acute abdomen in single center, and were
      determined to have SBPs due to unusual causes, were investigated retrospectively.
      Patients with aetiological factors such as trauma, mesenteric vascular disease,
      internal and external hernias, intra abdominal adhesions, inflammatory bowel
      diseases, and iatrogenic causes were excluded. Results: In total, 35 patients
      were evaluated, 20 (57.1%) males and 15 (42.9%) females. The mean age of the
      cases was 51.6 (18-88) years. Mean time until admission at the hospital was 1.4
      days (range 0.25-7 days). The most frequent aetiological factors were various
      malignancies (10 cases, 28.5%) and perforation of Meckel's diverticulum (8 cases,
      22.8%). It was surprising to detect a considerable rate of perforation due to
      bezoars (6 patients, 17.1%). Conclusions: Post-operative consequences of SBPs due
      to unusual causes are similar with those related to common, known causes. Factors
      affecting the clinical course are presentation time and patients' clinical status
      in admission, not aetiology.

PMID- 30190766
TI  - Prevalence and factors associated with smartphone addiction among medical
      students at King Abdulaziz University, Jeddah.
AB  - Objective: To investigate smartphone addiction among medical students and to
      determine factors associated with smartphone addiction among sixth-year medical
      students at King Abdulaziz University, Jeddah. Methods: This cross-sectional
      study was conducted on 203 sixth-year medical students at the Faculty of
      Medicine, King Abdulaziz University, Jeddah, Saudi Arabia, during July 2017. Data
      analysis was done using SPSS-20. Results: The number of completed questionnaires
      received was181 out of 203, making a response rate of 89%. There were 87 male
      respondents (48.1%) and 94 female respondents (51.9%). The overall prevalence of
      smartphone addiction was 66 (36.5%). There is a statistically significant
      relationship between daily hours of smartphone usage and smartphone addiction
      (p<0.02). Out of 66 addicted students, 24 (55.8%) students reported using their
      smartphone more than five hours daily, 17(34.7%) students were using it 4 to 5
      hours daily, 13 (27.7%) students were using it 2 to 3 hours daily and 12(28.6%)
      students were using it less than two hours daily. The study showed no
      statistically significant relationship between smartphone addiction and smoking
      statusor degree of obesity. There was a significant association between the total
      score on the smartphone addiction scale and daily usage hours (p-value<0.005).
      Conclusion: The overall prevalence of smartphone addiction was high among our
      study participants. The smartphone addiction was associated with daily hours of
      smartphone usage.

PMID- 30190765
TI  - Subclinical Hypothyroidism among local adult obese population.
AB  - Objective: To determine the frequency of subclinical hypothyroidism in local
      adult obese population. Methods: The study was conducted at Hayatabad Medical
      Complex, Peshawar, from March, 2017 to August, 2017. All patients aged between 18
      and 60 years with BMI of more than 29kg/m2 were included in the study. Patients
      on lipid lowering drugs, with renal failure, hepatic failure and already
      diagnosed cases of thyroid dysfunction were excluded from the study. Thyroid
      functions were measured for all patients. Results: A total of 127 adults were
      included in the study in a consecutive manner. Mean age was 34.5 + 7.9 years of
      which 46.5% were male and 53.5% were female. Mean BMI was 32.05+/-2.06 kg/m2. The
      mean serum TSH was 3.13+/-1.10 mIU/L and mean serum thyroxine level was 1.08+/
      0.25ng/dl. Subclinical hypothyroidism was recorded in 15% of the study
      population. Conclusion: Subclinical hypothyroidism is highly prevalent in our
      population with BMI of more than 29kg/m2. Further studies are recommended on
      relationship between thyroid functions and BMI and its effect on cardiovascular
      functions.

PMID- 30190767
TI  - Perinatal outcome among fasting and non fasting mothers during the month of
      Ramadan.
AB  - Objective: To compare the perinatal outcome among fasting and non fasting
      pregnant mothers. Methods: A total of 180 women, who came for delivery in the
      labor suite were included, after verbal informed consent. These women were
      divided in two groups fasting (n=100), and non-fasting (n=80). Results: The mean
      age of the mothers was 27.16+/-4.27 years in the fasting group and 27.36+/-4.92
      years in non-fasting group. The average BMI of mothers was 25.31+/-3.26 kg/m2in
      fasting group while 25.64+/-3.58 kg/m2in non-fasting group. Perinatal outcomes,
      the birth weight, head circumference and mid arm circumference were almost
      similar between the two groups. Weight of placenta was 537.80+/-80.01g in fasting
      group while 540.50+/-84.29 g in non-fasting group and height of baby was 45.79+/
      3.07 cm in fasting group while 46.61+/-2.92 cm in non-fasting group. In fasting
      group, placenta weight was 531.5+/-92.80 g in boys while 544.8+/-62.79 g in girls
      and ratio of placental to birth weight was 18.8+/-2.28 in boys while 19.4+/-2.70
      in girls. Conclusion: Maternal fasting affects placental weight and length of
      baby, with effect more pronounced in male babies.

PMID- 30190768
TI  - Effects of serum N-terminal pro B-type natriuretic peptide and D-dimer levels on
      patients with acute ischemic stroke.
AB  - Objective: To detect the serum levels of D-dimer and N-terminal pro B-type
      natriuretic peptide (NT-pro BNP) in patients with Acute Ischemic Stroke (AIS),
      and to explore the risk factors of AIS. Methods: A total of 246 AIS patients
      treated in our hospital from January 2015 to January 2017 were selected.
      Meanwhile, 240 healthy subjects were selected as a control group. The D-dimer and
      NT-pro BNP levels of the two groups were compared. Correlations of such levels
      with age, gender, blood lipid, Intima-Media Thickness (IMT), fibrinogen and
      degree of neurological deficits were analyzed. Results: The AIS group had
      significantly higher levels of Triglyceride (TG), Low-Density Lipoprotein (LDL),
      D-dimer, NT-pro BNP and fibrinogen as well as IMT than those of the control
      group, but the High-Density Lipoprotein (HDL) level of the AIS group was
      significantly lower (P<0.05). The patients with different genders and ages had
      significantly different D-dimer and NT-pro BNP levels (P<0.05). The D-dimer and
      NT-pro BNP levels were correlated with gender and age. Such levels of females
      were significantly higher than those of males (P<0.05). The D-dimer and NT-pro
      BNP levels of the >=60 years old group significantly exceeded those of the <60
      years old group (P<0.05). The levels of D-dimer and NT-pro BNP were negatively
      correlated with that of HDL (P<0.05), but positively correlated with TG, LDL and
      fibrinogen levels, IMT, and National Institutes of Health Stroke Scale score
      (P<0.05). Multivariate Logistic regression analysis showed that the OR values of
      D-dimer and NT-pro BNP were 3.65 and 6.96 respectively. Conclusion: Serum D-dimer
      and NT-pro BNP levels usually increased in AIS patients, and the levels were
      significantly correlated with AIS onset.

PMID- 30190769
TI  - The influence of patient-physician communication on physician loyalty and
      hospital loyalty of the patient.
AB  - Objective: Patient-physician communication is important for an effective
      healthcare service and for the patient's development of loyalty to the hospital.
      In this regard, this study aimed to determine whether there is a relationship
      between the patient-physician communication, the loyalty of the patient to the
      physician and to the hospital. Also study aimed to determine whether there is a
      mediating role of the physician loyalty on the patient-physician communication
      effect on to the hospital loyalty. Method: Five hundred ten questionnaires were
      distributed to regular public patients of the government hospitals, clinics, and
      private clinic patients in Sakarya using a simple random sampling method. Data
      were analysed using descriptive statistics and Structural Equation Modelling
      (SEM). Results: According to the findings, there was a significant relationship
      between patient-physician communication and loyalty to physician and to hospital.
      Patient-physician communication has a significant effect on loyalty to physician
      and hospital. In addition, patient loyalty has a mediating role on the patient
      physician communication effect on the hospital loyalty. Conclusion: According to
      the result of the study, physician-patient communication could be used as an
      important tool in creating physician loyalty and hospital loyalty. This study
      helps physicians and health service providers to formulate strategies and tactics
      that will effectively develop the loyalty of patients.

PMID- 30190770
TI  - Predictors of serious findings on bi-directional endoscopy in young patients with
      anemia and GI symptoms.
AB  - Background and Objective: Iron deficiency anemia (IDA) has been cited as the most
      common cause of anemia globally. Gastrointestinal (GI) lesions are amongst the
      common cause of IDA. Endoscopic evaluation is the most effective way to
      investigate the IDA. The aim of this study was to show the association of
      alarming GI symptoms with abnormal endoscopic findings and to cut off the burden
      and cost of unnecessary endoscopies. Methods: This is cross sectional study of
      anemic patient who underwent upper and lower GI endoscopies in Aga Khan
      University Hospital, Karachi between July-December 2016. Results: Total 243
      patients were identified after excluding ineligible patients. The mean age of
      subjects was 31.9 +/- 6.1 years with a slight over-representation of females
      (57.4%). 149 (61.31%) patients underwent only upper GI endoscopic evaluation, and
      83 (34.15%) patients on whom bi-directional endoscopy was performed (upper and
      lower). The remaining 11 (4.52%) patients underwent colonoscopy only. 16 (6.6%)
      subjects had negative findings on evaluation, while gastritis and serious
      findings were observed in 175 (72.0%) and 52 (21.4%) patients respectively. We
      found that patients with alarm features such as dysphagia (aOR: 2.07, 95%CI: 0.12
      34.1), altered bowel habits (aOR: 1.64, 95%CI: 0.44-6.09) and weight loss (aOR:
      1.25 95%CI: 0.54-2.85) demonstrated higher odds of serious findings on endoscopic
      evaluation as compared to the reference category, however they were not
      independently associated. Conclusion: Most of our patients had non-malignant
      pathologies, while alarm features were not found to be useful predictors of
      serious findings.

PMID- 30190771
TI  - Treatment of unruptured cornual pregnancies by local injections of methotrexate
      or potassium chloride under transvaginal ultrasonographic guidance.
AB  - Objective: To demonstrate the outcome of intralesional management and show the
      safety of local treatment of cornual pregnancy. Methods: Eight patients were
      treated with local methotrexate or potassium chloride injection. All patients
      underwent transvaginal ultrasound examination and were diagnosed by the criteria
      defined by Timor-Tritsch. In the case of fetal heart beat observation, potassium
      chloride was injected; and in the case of no heart beat detection, methotrexate
      was used. A follicle aspiration needle was inserted directly into the gestational
      sac under transvaginal guidance. Results: Although it has been considered to be a
      risk factor, none of the patients in our study had previous ectopic pregnancy,
      history of infertility / in vitro fertilization, or cornual pregnancy. One of the
      patients had a medical history of abortion. In four cases, methotrexate was
      injected, and three patients received potassium chloride as a local treatment.
      None of the patients had any complication in the peri- or postoperative period.
      Conclusion: Using a local approach, the treatment agent can reach the area of the
      cornual pregnancy in high concentrations. Based on this case series, a local
      approach seems to be an effective and fertility-sparing method for treating
      unruptured cornual pregnancies.

PMID- 30190772
TI  - L-Dopa response to Cortical Dysfunctions, health related quality of life and
      Fatigue Severity in Idiopathic Parkinson's disease.
AB  - Objectives: To determine (i) levodopa (L-Dopa) responsiveness on cortical
      functions, health related quality of life and fatigue severity (ii) relationship
      between cortical functions, health related quality of life and fatigue severity
      post L-Dopa treatment of patients with idiopathic Parkinson's Disease (I-PD).
      Methods: Participants included 50 patients diagnosed with I-PD who were attending
      Civil and Bahawal Victoria Hospital, Bahawalpur, Pakistan during May 2016 to July
      2017 and 50 healthy individuals (HI) took part in the study. Participants
      completed Cortical Function Assessment, Parkinson's Disease Questionnaire and
      Fatigue Severity Scale. Patients were tested twice on these measures: pre and
      post- L-Dopa treatment. Results: Patients with I-PD showed cortical functioning
      deficits, deteriorated health related quality of life and experience of severe
      fatigue, in contrast with HI. There was significant improvement in cortical
      functioning and quality of life while reduction in fatigue severity was observed
      after three months of L-Dopa medication in I- PD patients. Higher cortical
      functioning deficits correlated with deteriorated health related quality of life
      and severe fatigue. Cortical functioning was a significant predictor of health
      related quality of life and fatigue severity. Conclusion: L-Dopa is an effective
      treatment for cortical dysfunctions, health related quality of life and fatigue
      in I-PD. Cortical functioning is a significant marker of quality of life and
      fatigue in patients with I-PD.

PMID- 30190774
TI  - An elusive case of digital ischemia in a patient with Rheumatoid Arthritis.
AB  - Essential thrombocytosis (ET) has rarely been reported with autoimmune rheumatic
      disorders. We report a case of young female, diagnosed case of Rheumatoid
      arthritis (RA), who had been overlooked for her raised platelet counts. Later her
      symptoms of impending digital gangrene led to an active search for her
      thrombocytosis. JAK2 mutation came out to be positive and she was diagnosed as ET
      associated with RA. She was treated with Hydroxyurea and Aspirin, in addition to
      her RA treatment. Patient responded well to the treatment and her platelet counts
      have been gradually improved, however, she developed gangrene of toe, for which
      amputation of distal phalanx of toe and nail excision was done, later in the
      disease course.

PMID- 30190773
TI  - Upper lip bite test for prediction of difficult airway: A systematic review.
AB  - Background and Objective: Upper lip bite test (ULBT) is one of the various
      bedside tests used for prediction of difficult laryngoscopic intubation. However,
      its usefulness is not still very clear, and there is controversy regarding its
      accuracy. The aim of this systematic review was to determine the accuracy of the
      ULBT for predicting difficult airway including difficult laryngoscopy or
      difficult tracheal intubation. Method: We searched the databases of PubMed,
      Scopus, and Google scholar for prospective studies published up until October
      2016 assessing the accuracy of ULBT in comparison to Cormack-Lehane grading. The
      selected keywords were "upper lip bite test", "upper lip catch test",
      "prediction", "difficult airway", "difficult laryngoscopy", "difficult
      intubation". Inclusion criteria were studies assessing ULBT for prediction of
      difficult intubation, considering Cormack-Lehane grade III and IV as difficult
      airway, written in English, and reporting sensitivity, specificity, NPV, PPV, and
      accuracy. Exclusion criteria were studies not reporting accuracy or not having
      enough data for its calculation. Based on the mentioned criteria, 27 studies
      enrolling 18141 patients were included. This systematic review was performed
      based on the guidelines on conducting systematic reviews of diagnostic studies.
      Results: Prevalence of airway difficulties according to the direct laryngoscopic
      view varied from 2.8% to 27% and according to the ULBT was from 2% to 21%. In 11
      of the 27 studies, sensitivity of ULBT in prediction of difficult airway was more
      than 70%. All of the studies except one showed a high specificity for ULBT
      (>85%). Moreover, these studies indicated a high NPV. Accuracy of ULBT was >85%
      in 24 out of 27 studies. Conclusion: It appears that ULBT is a useful bedside
      test for evaluation of patient airway before the general anesthesia.

PMID- 30190775
TI  - Fournier gangrene due to Rhizobium Radiobacter.
AB  - Fournier's gangrene (FG) is a life-threatening, rapidly progressing acute
      necrotizing fasciitis of perianal, genitourinary and perineal areas. The most
      common isolated pathogens are E.coli, Streptococcus and Enterococcus in tissue
      and abscess cultures. However we present the first Rhizobium radiobacter FG in
      this case. A 47-year-old man presented with black necrotizing area with
      malodorous pus drainage in the bottom of the right hemiscrotum. Intravenous
      imipenem and Clindamycin were started prophylactically; all necrotizing tissues
      were debrided and right hemiscrotectomy was performed. Rhizobium radiobacter was
      isolated from tissue and abscess cultures. After successful treatment patient was
      discharged posteroperative 18th day. The combination therapy of early and totally
      surgical debridement of necrotic tissues and appropriate antibiotic use are
      adequate to control Rhizobium radiobacter infection in FG.

PMID- 30190776
TI  - Germ cell tumor and Takotsubo Cardiomyopathy: A treatment dilemma.
AB  - Germ cell tumors (GCT) are uncommon malignancies in adult males and comprise less
      than 1% of male cancers. Due to highly curative nature and productive life years
      gained after treatment; reduction of chemotherapy related toxicities becomes
      vital. Cisplatin is the backbone of GCT chemotherapy, & is related to myocardial
      injury, thromboembolism & vasculitis. Though it should not be replaced with
      Carboplatin, however in certain circumstances, its use maybe unsafe; especially
      in cases when patient have prior myocardial infarction. We report a case of
      Takotsubo cardiomyopathy (TCM)secondary to GCT diagnosis in a young male. This
      patient presented with symptoms of myocardial infarction however, coronary
      angiography was normal and a diagnosis of TCM was made. Though, it is rare but a
      unique challenge, as whether Cisplatin use would be safe in this particular
      scenario? On one hand patient had stress related myocardial injury while he was
      also at risk of further Cisplatin induced complications. There are no clear cut
      guidelines, so after informed consent his treatment regimen was modified to EC
      (Etoposide/Carboplatin) instead of EP (Etoposide/Cisplatin). Patient has
      completed 4.6 years of follow-up without any evidence of relapse. We suggest
      informed decisions and to weigh the pros and cons of using an inferior regimen,
      in order to achieve same long term prognosis while preventing any acute
      complications, in younger patients with curable cancers.

PMID- 30190777
TI  - What is a university education?

PMID- 30190778
TI  - Proceedings of Workshop on Scientific Writing and Publishing organized by EMAME
      DHA at Dubai (March 22-24th 2018).

PMID- 30190779
TI  - Proceedings of National Medical Conference organized by Azra Naheed Medical
      College in collaboration with Pakistan Aspirin Foundation (April 28th 2018).

PMID- 30190780
TI  - Stem cell-derived exosomes - an emerging tool for myocardial regeneration.
AB  - Cardiovascular diseases (CVDs) continue to represent the number one cause of
      death and disability in industrialized countries. The most severe form of CVD is
      acute myocardial infarction (AMI), a devastating disease associated with high
      mortality and disability. In a substantial proportion of patients who survive
      AMI, loss of functional cardiomyocytes as a result of ischaemic injury leads to
      ventricular failure, resulting in significant alteration to quality of life and
      increased mortality. Therefore, many attempts have been made in recent years to
      identify new tools for the regeneration of functional cardiomyocytes.
      Regenerative therapy currently represents the ultimate goal for restoring the
      function of damaged myocardium by stimulating the regeneration of the infarcted
      tissue or by providing cells that can generate new myocardial tissue to replace
      the damaged tissue. Stem cells (SCs) have been proposed as a viable therapy
      option in these cases. However, despite the great enthusiasm at the beginning of
      the SC era, justified by promising initial results, this therapy has failed to
      demonstrate a significant benefit in large clinical trials. One interesting
      finding of SC studies is that exosomes released by mesenchymal SCs (MSCs) are
      able to enhance the viability of cardiomyocytes after ischaemia/reperfusion
      injury, suggesting that the beneficial effects of MSCs in the recovery of
      functional myocardium could be related to their capacity to secrete exosomes. Ten
      years ago, it was discovered that exosomes have the unique property of
      transferring miRNA between cells, acting as miRNA nanocarriers. Therefore,
      exosome-based therapy has recently been proposed as an emerging tool for cardiac
      regeneration as an alternative to SC therapy in the post-infarction period. This
      review aims to discuss the emerging role of exosomes in developing innovative
      therapies for cardiac regeneration as well as their potential role as candidate
      biomarkers or for developing new diagnostic tools.

PMID- 30190782
TI  - Approach to pseudomyxoma peritonei.
AB  - Pseudomyxoma peritonei (PMP) is a mucinous tumour of the appendix that spreads
      into the peritoneal cavity in the form of gelatinous deposits. The incidence of
      PMP is believed to be approximately 1-3 out of a million per year. Nonetheless,
      due to its indolent nature, it is usually discovered at an advanced stage and
      severely impacts quality of life. Curative treatment for PMP is complete
      cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy
      (HIPEC). An extensive literature review was conducted searching EMBASE, MEDLINE,
      PubMed, and Google Scholar databases for PMP in aims to delineate a clinical
      approach to diagnosis and treatment. Literature was limited to the years 2007
      2018. We found the 5-year overall survival with CRS and HIPEC estimated to be
      between 23%-82% and rates of major complications as high as 24%. Therefore, it is
      important to appropriately stage and select patients that should undergo CRS with
      HIPEC. Modalities like MDCT radiological scores have been shown to have
      sensitivity and specificity of 94% and 81%, respectively, in being able to
      predict resectability and survival. Despite treatment, the disease often recurs.
      Tumor markers have significant potential for establishing prognosis pre
      operatively, and this paper will review the most recent evidence in support of
      them.

PMID- 30190783
TI  - Prophylactic cranial irradiation (PCI) in locally advanced non-small cell lung
      cancer: time for hope?

PMID- 30190784
TI  - Disabling an oncogenic transcription factor by targeting of control kinases.

PMID- 30190785
TI  - A metabolic vulnerability of small-cell lung cancer.

PMID- 30190781
TI  - Current status of imaging in nonalcoholic fatty liver disease.
AB  - Non-alcoholic fatty liver disease (NAFLD) is the most common diffuse liver
      disease, with a worldwide prevalence of 20% to 46%. NAFLD can be subdivided into
      simple steatosis and nonalcoholic steatohepatitis. Most cases of simple steatosis
      are non-progressive, whereas nonalcoholic steatohepatitis may result in chronic
      liver injury and progressive fibrosis in a significant minority. Effective risk
      stratification and management of NAFLD requires evaluation of hepatic parenchymal
      fat, fibrosis, and inflammation. Liver biopsy remains the current gold standard;
      however, non-invasive imaging methods are rapidly evolving and may replace biopsy
      in some circumstances. These methods include well-established techniques, such as
      conventional ultrasonography, computed tomography, and magnetic resonance imaging
      and newer imaging technologies, such as ultrasound elastography, quantitative
      ultrasound techniques, magnetic resonance elastography, and magnetic resonance
      based fat quantitation techniques. The aim of this article is to review the
      current status of imaging methods for NAFLD risk stratification and management,
      including their diagnostic accuracy, limitations, and practical applicability.

PMID- 30190786
TI  - xCT inhibition sensitizes tumors to gamma-radiation via glutathione reduction.
AB  - About 3 million US cancer patients and 1.7 million EU cancer patients received
      multiple doses of radiation therapy (RT) in 2012, with treatment duration limited
      by normal adjacent tissue damage. Tumor-specific sensitization could allow
      treatment with lower radiation doses, reducing normal tissue damage. This is a
      longstanding, largely unrealized therapeutic goal. The cystine:glutamate
      exchanger xCT is expressed on poor prognosis subsets of most solid tumors, but
      not on most normal cells. xCT provides cells with environmental cystine for
      enhanced glutathione synthesis. Glutathione is used to control reactive oxygen
      species (ROS), which are therapeutic effectors of RT. We tested whether xCT
      inhibition would sensitize xCT+ tumor cells to ionizing radiation. We found that
      pretreatment with the xCT inhibitor erastin potently sensitized xCT+ but not xCT-
      cells, in vitro and in xenograft. Similarly, targeted gene inactivation also
      sensitized cells, and both modes of sensitization were overcome by glutathione
      supplementation. Sensitization prolongs DNA damage signaling, increases genome
      instability, and enhances cell death, revealing an unforeseen role for cysteine
      in genome integrity maintenance. We conclude that an xCT-specific therapeutic
      would provide tumor-specific sensitization to RT, allowing treatment with lower
      radiation doses, and producing far fewer side effects than other proposed
      sensitizers. Our data speaks to the need for the rapid development of such a
      drug.

PMID- 30190787
TI  - Immune checkpoint inhibitor re-challenge in patients with advanced non-small cell
      lung cancer.
AB  - Background: Immune checkpoint inhibitors have dramatically changed lung cancer
      treatment, demonstrating an overall survival benefit. There are limited data
      about re-challenge in patients with non-small cell lung cancer. We attempted to
      address this question for re-challenge of immune checkpoint inhibitor in patients
      with advanced non-small cell lung cancer. Methods: We retrospectively analyzed 11
      patients with advanced non-small cell lung cancer treated with nivolumab and re
      challenged with nivolumab/pemblorizumab at Kansai Medical University Hospital
      from December 2015 to December 2017. Results: Three patients achieved PR and two
      patients were in SD. These patients were apt to be good responders to the initial
      treatment, to develop immune-related adverse events and to be immediately started
      on re-challenge with immune checkpoint inhibitor. The median PFS was 2.7 (range,
      0.5-16.1) months. Five patients (45%) had mild to moderate immune-related adverse
      events. Conclusion: Our study shows the effectiveness of re-challenge of immune
      checkpoint inhibitors in a subset of non-small cell lung cancer patients. Re
      challenge might become one of treatment option for advanced non-small cell lung
      cancer.

PMID- 30190789
TI  - Race and nodal disease status are prognostic factors in patients with stage IVB
      cervical cancer.
AB  - Background: Patients presenting with stage IVB cervical cancer pose a significant
      clinical challenge. While previous studies described several poor prognostic
      factors, they were limited by small sample sizes. The aim of this study was to
      identify clinicopathological prognostic factors in a large sample of patients
      with stage IVB cervical cancer at a single institution. Methods: Patients with
      primary stage IVB cervical cancer diagnosed between 1992 and 2011 were extracted
      from a search of the MD Anderson Cancer Center registry. Clinicopathological data
      retrieved from their medical records included demographics (age and race), tumor
      characteristics (primary lesion size, grade, and histology), TNM classification,
      and metastatic site (nodal/organ). Treatment approach (radiation, chemotherapy,
      or both) and intent (palliation or curative) were recorded. Survival rates were
      evaluated using the Kaplan-Meier method. Cox proportional hazards regression was
      used to model the association between key variables and overall survival (OS).
      Results: Two hundred sixty-six patients with stage IVB cervical cancer were
      identified. Their median OS was 12.7 months. The hazard ratio for African
      Americans vs. patients with other ethnicities was 1.76 (95% confidence interval
      [CI], 1.18-2.54, P = 0.0063), and that for patients with para-aortic nodes alone
      vs. more extensive metastases was 0.37 (95% CI, 0.26-0.51, P < 0.0001). Other
      clinicopathological factors were not significantly associated with survival.
      Conclusions: African-American race was an independent adverse prognostic factor
      in this cohort. On the other hand, nodal disease in the para-aortic chain alone
      predicted a favorable prognosis.

PMID- 30190788
TI  - Terpenes from essential oils and hydrolate of Teucrium alopecurus triggered
      apoptotic events dependent on caspases activation and PARP cleavage in human
      colon cancer cells through decreased protein expressions.
AB  - This study focused on characterizing the Hydrophobic and Hydrophilic fractions of
      Teucrium alopecurus in the context of cancer prevention and therapy. The goal was
      also to elucidate the molecular mechanisms involved and to determine its efficacy
      against cancer by triggering apoptosis and suppressing tumorigenesis in human
      colon cancer. The data here clearly demonstrated that oily fractions of Teucrium
      alopecurus act as free radical scavengers, antibacterial agent and inhibited the
      proliferation of HCT-116, U266, SCC4, Panc28, KBM5, and MCF-7 cells in a time-
      and concentration-dependent manner. The results of live/dead and colony formation
      assays further revealed that Teucrium essential oil has the efficacy to suppress
      the growth of colon carcinoma cells. In addition, essential oil of Teucrium
      alopecurus induced apoptosis, as indicated by cleavage of caspases-3, -8, and -9
      and poly-adenosine diphosphate ribose polymerase. Moreover, Teucrium alopecurus
      essential oil suppressed gene expression involved in survival, proliferation,
      invasion, angiogenesis, and metastasis in human colon cancer cells. No sign of
      toxicity was detected in vivo after treatment with increasing concentrations of
      essential oil. Oral administration of T.alopecurus inhibited LPS-induced colon
      inflammation. This anticancer property of this specie Teucrium alopecurus
      fractions could be due to their phenolic and/or sesquiterpene content (d
      limonene, alpha-Bisabolol, Humulene, Thymol, and (+)-epi
      Bicyclosesquiphellandrene). Hence our study reveals the anticancer activity of
      Teucrium alopecurus oil mediated through the suppression of cell growth, cell
      proliferation, and the induction of apoptosis of cancer cells. Thus, it has
      potential to be developed as an anticancer agent; however more in vitro and in
      vivo studies are warranted.

PMID- 30190790
TI  - Snail mediates repression of the Dlk1-Dio3 locus in lung tumor-infiltrating
      immune cells.
AB  - The epithelial-mesenchymal transition-inducing transcription factor Snail
      contributes to tumor progression in different malignancies. In the present study,
      we used a transcriptomics approach to elucidate the mechanism of Snail-mediated
      tumor growth promotion in a KrasLSL-G12D/+;p53fl/fl mouse model of lung
      adenocarcinoma. We discovered that Snail mediated the downregulation of the
      imprinted Dlk1-Dio3 locus, a complex genomic region containing protein-coding
      genes and non-coding RNAs that has been linked to tumor malignancy in lung cancer
      patients. The Dlk1-Dio3 locus repression mediated by Snail was found to occur
      specifically in several populations of tumor-infiltrating immune cells. It could
      be reproduced in primary splenocytes upon ex vivo culture with conditioned medium
      from Snail-expressing cancer cell lines, which suggests that a Snail-induced
      soluble factor secreted by the cancer cells mediates the Dlk1-Dio3 locus
      repression in immune cells, particularly in lymphocytes. Our findings furthermore
      point towards the contribution of Snail to an inflammatory tumor
      microenvironment, which is in line with our previous report of the Snail-mediated
      recruitment of pro-tumorigenic neutrophils to the lung tumors. This underlines an
      important role for Snail in influencing the immune compartment of lung tumors and
      thus contributing to disease progression.

PMID- 30190791
TI  - Online structure-based screening of purchasable approved drugs and natural
      compounds: retrospective examples of drug repositioning on cancer targets.
AB  - Drug discovery is a long and difficult process that benefits from the integration
      of virtual screening methods in experimental screening campaigns such as to
      generate testable hypotheses, accelerate and/or reduce the cost of drug
      development. Current drug attrition rate is still a major issue in all
      therapeutic areas and especially in the field of cancer. Drug repositioning as
      well as the screening of natural compounds constitute promising approaches to
      accelerate and improve the success rate of drug discovery. We developed three
      compounds libraries of purchasable compounds: Drugs-lib, FOOD-lib and NP-lib that
      contain approved drugs, food constituents and natural products, respectively,
      that are optimized for structure-based virtual screening studies. The three
      compounds libraries are implemented in the MTiOpenScreen web server that allows
      users to perform structure-based virtual screening computations on their selected
      protein targets. The server outputs a list of 1,500 molecules with predicted
      binding scores that can then be processed further by the users and purchased for
      experimental validation. To illustrate the potential of our service for drug
      repositioning endeavours, we selected five recently published drugs that have
      been repositioned in vitro and/or in vivo on cancer targets. For each drug, we
      used the MTiOpenScreen service to screen the Drugs-lib collection against the
      corresponding anti-cancer target and we show that our protocol is able to rank
      these drugs within the top ranked compounds. This web server should assist the
      discovery of promising molecules that could benefit patients, with faster
      development times, and reduced costs and risk.

PMID- 30190792
TI  - RNA based individualized drug selection in breast cancer patients without patient
      matched normal tissue.
AB  - Background: While standard RNA expression tests stratify patients into risk
      groups, RNA-Seq can guide personalized drug selection based on expressed
      mutations, fusion genes, and differential expression (DE) between tumor and
      normal tissue. However, patient-matched normal tissue may be unavailable.
      Additionally, biological variability in normal tissue and technological biases
      may confound results. Therefore, we present normal expression reference data for
      two sequencing methods that are suitable for breast biopsies. Results: We
      identified breast cancer related and drug related genes that are expressed
      uniformly across our normal samples. Large subsets of these genes are identical
      for formalin fixed paraffin embedded samples and fresh frozen samples. Adipocyte
      signatures were detected in frozen compared to formalin samples, prepared by
      surgeons and pathologists, respectively. Gene expression confounded by adipocytes
      was identified using fat tissue samples. Finally, immune repertoire statistics
      were obtained for healthy breast, tumor and fat tissues. Conclusions: Our
      reference data can be used with patient tumor samples that are asservated and
      sequenced with a matching aforementioned method. Coefficients of variation are
      given for normal gene expression. Thus, potential drug selection can be based on
      confidently overexpressed genes and immune repertoire statistics. Materials and
      Methods: Normal expression from formalin and frozen healthy breast tissue samples
      using Roche Kapa RiboErase (total RNA) (19 formalin, 9 frozen) and Illumina
      TruSeq RNA Access (targeted RNA-Seq, aka TruSeq RNA Exome) (11 formalin, 1
      frozen), and fat tissue (6 frozen Access). Tumor DE using 10 formalin total RNA
      tumor samples and 1 frozen targeted RNA tumor sample.

PMID- 30190793
TI  - Association between red and processed meat intake and colorectal adenoma
      incidence and recurrence: a systematic review and meta-analysis.
AB  - The associations between red and processed meat intake and colorectal adenoma
      (CRA) incidence and recurrence are inconclusive. We performed a systematic review
      and meta-analysis to analysis these associations. We conducted a systematic
      search of PubMed, EMBASE and Web of Science up to December 2016. The relative
      risks (RRs) and 95% confidence intervals (CIs) were assessed. Subgroup analyses,
      dose-response-analyses, subtype analyses and analyses of CRA locations were also
      conducted. Twenty-seven studies that involved 208,117 participants and 19,150
      cases met criteria. The RRs of the highest versus lowest intakes for CRA
      incidence were 1.23 (1.15-1.31) for red meat and 1.15 (1.07-1.24) for processed
      meat. Dose-response analyses for meat per 100 g/day yielded the results were
      consistent with the original analyses, with 1.14 (1.07-1.20) for red meat and
      1.27 (1.03-1.50) for processed meat. Additionally, there were no associations
      between red and processed meat intake and CRA recurrence, including total CRA (P
      > 0.05), advanced CRA (P > 0.05) and multiple CRA (P > 0.05). In conclusion, our
      findings support the hypothesis that red and processed meat intake was associated
      with an increased CRA incidence but not for CRA recurrence.

PMID- 30190795
TI  - Erratum: Will PI3K pathway inhibitors be effective as single agents in patients
      with cancer?
AB  - [This corrects the article DOI: 10.18632/oncotarget.409.].

PMID- 30190794
TI  - Spanish Lymphoma Group (GELTAMO) guidelines for the diagnosis, staging,
      treatment, and follow-up of diffuse large B-cell lymphoma.
AB  - Diffuse large B-cell lymphoma (DLBCL) accounts for approximately 30% of non
      Hodgkin lymphoma (NHL) cases in adult series. DLBCL is characterized by marked
      clinical and biological heterogeneity, encompassing up to 16 distinct
      clinicopathological entities. While current treatments are effective in 60% to
      70% of patients, those who are resistant to treatment continue to die from this
      disease. An expert panel performed a systematic review of all data on the
      diagnosis, prognosis, and treatment of DLBCL published in PubMed, EMBASE and
      MEDLINE up to December 2017. Recommendations were classified in accordance with
      the Grading of Recommendations Assessment Development and Evaluation (GRADE)
      framework, and the proposed recommendations incorporated into practical
      algorithms. Initial discussions between experts began in March 2016, and a final
      consensus was reached in November 2017. The final document was reviewed by all
      authors in February 2018 and by the Scientific Committee of the Spanish Lymphoma
      Group GELTAMO.

PMID- 30190796
TI  - Correction: Antigen-specific T cell Redirectors: a nanoparticle based approach
      for redirecting T cells.
AB  - [This corrects the article DOI: 10.18632/oncotarget.11785.].

PMID- 30190797
TI  - Correction: Systematic discovery of drug action mechanisms by an integrated
      chemical genomics approach: identification of functional disparities between
      azacytidine and decitabine.
AB  - [This corrects the article DOI: 10.18632/oncotarget.8455.].

PMID- 30190798
TI  - Correction: Loss of EGFR signaling-regulated miR-203 promotes prostate cancer
      bone metastasis and tyrosine kinase inhibitors resistance.
AB  - [This corrects the article DOI: 10.18632/oncotarget.1994.].

PMID- 30190800
TI  - In vivo evaluation of early renal damage in type 2 diabetic patients on 3.0 T MR
      diffusion tensor imaging.
AB  - AIM: To investigate the utility of renal diffusion tensor imaging (DTI) to detect
      early renal damage in patients with type 2 diabetes. METHODS: Twenty-six diabetic
      patients (12 with microalbuminuria (MAU), and 14 with normoalbuminuria) and
      fourteen healthy volunteers were prospectively included in this study. Renal DTI
      on 3.0 T MR was performed, and estimated glomerular filtration rate (eGFR) was
      recorded for each subject. Mean cortical and medullary fractional anisotropy (FA)
      values were calculated by placing multiple representative regions of interest.
      Mean FA values were statistically compared among groups. Correlations between FA
      values and eGFR were evaluated. RESULTS: Both cortical and medullary FA were
      significantly reduced in diabetic patients compared to healthy controls (0.403 +/
      0.064 vs 0.463 +/- 0.047, P = 0.004, and 0.556 +/- 0.084 vs 0.645 +/- 0.076, P =
      0.002, respectively). Cortical FA was significantly lower in diabetic patients
      with NAU than healthy controls (0.412 +/- 0.068 vs 0.463 +/- 0.047, P = 0.02).
      Medullary FA in diabetic patients with NAU and healthy controls were similar
      (0.582 +/- 0.096 vs 0.645 +/- 0.076, P = 0.06). Both cortical FA and medullary FA
      correlated with eGFR (r = 0.382, P = 0.015 and r = 0.552, P = 0.000,
      respectively). CONCLUSION: FA of renal parenchyma on DTI might serve as a more
      sensitive biomarker of early diabetic nephropathy than MAU.

PMID- 30190801
TI  - Making sense of the melanoma information tsunami.

PMID- 30190802
TI  - Advances in molecular profiling of malignant melanoma: ready for clinical
      practice?

PMID- 30190799
TI  - Newer echocardiographic techniques for aortic-valve imaging: Clinical aids today,
      clinical practice tomorrow.
AB  - Increasing life expectancy is expected to lead to a corresponding increase in the
      prevalence of aortic valve disease (AVD). Further, the number of indications for
      transcatheter aortic valve replacement (TAVR) as a treatment option for AVD is
      expanding, with a growing role for echocardiography in its management. In this
      review we summarize the current literature on some newer echocardiographic
      modalities and the parameters they generate, with a particular focus on their
      prognostic and clinical value beyond conventional methods in the management of
      aortic stenosis, TAVR, and aortic regurgitation. Speckle tracking and 3D
      echocardiography are now increasingly being used in the management of AVD. For
      instance, global longitudinal strain, the best-studied speckle tracking
      echocardiographic parameter, can detect subtle subclinical cardiac dysfunction in
      patients with AVD that is not apparent using traditional echocardiographic
      techniques. The emerging technique of 3D full volume color Doppler
      echocardiography provides more accurate measurement of the severity of aortic
      regurgitation than 2D-proximal isovelocity surface area. These novel techniques
      are promising for evaluating and risk stratifying patients to optimize surgical
      interventions, predict recovery, and improve clinical outcomes.

PMID- 30190803
TI  - High-risk cutaneous melanoma follow-up: time for more intensive surveillance?

PMID- 30190804
TI  - A blood test to identify when melanoma metastasizes: a reality for melanoma
      management?

PMID- 30190805
TI  - Where to start with systemic melanoma therapy?

PMID- 30190806
TI  - Advances in immunotherapy for melanoma.
AB  - Paolo A Ascierto obtained his MD from the University of Naples, Italy, where he
      earned board certification in oncology. He is currently Director at the Unit of
      Melanoma, Cancer Immunotherapy and Innovative Therapy Unit, National Tumor
      Institute 'Fondazione G. Pascale', Naples, Italy. Before his present position, he
      served consecutive positions there as a postdoctoral fellow and then as Vice
      Director of the Department of Clinical Immunology. His major research interests
      have included genetics and proteomics research of melanoma, apoptosis and cell
      death in human cancer and the assessment of molecular markers for tumor
      progression in melanoma, as well as the management of targeted therapies for
      melanoma, vaccination treatments and biochemical and immunological monitoring. He
      has served as a principal investigator in numerous clinical trials and has been
      widely published in peer-reviewed journals on topics related to his interests.
      Ascierto has been an invited speaker at more than 200 national and international
      meetings and is an active member of the Italian Society of Medical Oncology
      (AIOM), the American Society of Clinical Oncology (ASCO), the European Society of
      Medical Oncology (ESMO), the European Organisation for Research and Treatment of
      Cancer (EORTC) and the International Society for Biological Therapy of Cancer
      (iSBTc). He is also the Editor-in-Chief of the Combination Strategies section of
      the Journal of Translational Medicine and serves as a scientific reviewer for
      several journals. James Larkin is a consultant medical oncologist specializing in
      the treatment of patients with cancer of the kidney and cancers of the skin,
      including melanoma. Larkin obtained a first-class degree in Natural Sciences from
      Cambridge University and undertook clinical training at Oxford University,
      qualifying in 1996. He underwent general medical training in London and, in 2001,
      won a Medical Research Council Fellowship for a Clinician, carrying out
      laboratory research at the Institute of Cancer Research (ICR), which led to the
      awarding of his PhD. He completed specialist training at The Royal Marsden
      Hospital and was appointed as a consultant in 2008. His research interests
      include the individualization of patient treatment in renal cancer and melanoma
      and the combination of novel targeted therapies for the treatment these diseases.
      He is the UK Chief Investigator for a number of clinical trials in melanoma and
      kidney cancer and has been awarded research grants from bodies including Cancer
      Research UK, the Wellcome Trust and the European Framework Programme 7. He is a
      member of the National Cancer Research Institute (NCRI) Melanoma Clinical Studies
      Group and Chair of both the NCRI Renal Cancer Clinical Studies Group and The
      Royal Marsden/ICR Committee for Clinical Research.

PMID- 30190807
TI  - A melanoma odyssey - a conversation with Vernon Sondak about a career in melanoma
      treatment and research.
AB  - VERNON SONDAK* SPEAKS TO LAURA MCGUINNESS, MANAGING COMMISSIONING EDITOR: Vernon
      Sondak is Chair of the Department of Cutaneous Oncology and Director of Surgical
      Education at the H Lee Moffitt Cancer Center and Research Institute in Tampa, FL,
      USA. He is also a Professor in the Departments of Oncologic Sciences and Surgery
      at the University of South Florida Morsani College of Medicine. His research
      interests include the surgical treatment of malignant melanoma in adults and
      children; the surgical treatment of Merkel cell carcinoma, desmoid tumors and
      cutaneous soft-tissue sarcomas, including dermatofibrosarcoma protuberans; the
      adjuvant therapy of melanoma; and the evaluation of new therapies for patients
      with localized or disseminated melanoma. Sondak has also been a leader in studies
      of the surgical treatment of melanoma and other cutaneous malignancies,
      particularly in the application of sentinel lymph node biopsy to the staging of
      melanoma and Merkel cell carcinoma. He is actively involved in ongoing analyses
      in order to determine which patients with thin melanomas are most likely to
      benefit from sentinel node biopsy, as well as which patients with sentinel node
      metastases are most likely to have further metastases identified in other
      regional lymph nodes. Sondak is the author or coauthor of over 300 articles in
      peer-reviewed publications, 165 abstracts, eight books and 67 book chapters.

PMID- 30190808
TI  - Subcutaneous metastases from melanoma: a discussion of clinical experience.
AB  - The majority of locoregional relapses of cutaneous melanoma occur as subcutaneous
      local recurrences/in-transit metastases; subcutaneous metastases (SMs) are also
      common in distant metastases. SM therapy is challenging and depends on the
      number, site, depth, size, clinical behavior and presence of other metastases.
      Isolated, resectable SMs should be treated surgically. In multiple/unresectable
      lesions, several local modalities are used: carbon dioxide laser ablation,
      radiotherapy, cryotherapy, intralesional injections and electrochemotherapy.
      Hyperthermic isolated limb perfusion is the preferred method of treating
      multiple, bulky in-transit metastases in extremities, allowing for high response
      rates and long-lasting remission. Electrochemotherapy is a simple method for the
      fast ablation of SMs that are not feasible for hyperthermic isolated limb
      perfusion. Recent advances in systemic therapy of melanoma, including
      immunotherapy (anti-CTLA4/anti-PD-1) and targeted therapy (BRAF/MEK inhibitors),
      have significantly impacted on SM treatment. We present our own SM cases treated
      with different modalities. The future of SM therapy will rely on a combination of
      different local, locoregional and systemic modalities, and we can expect major
      improvements in long-term outcomes.

PMID- 30190809
TI  - No one should die of melanoma: a vision or impossible mission?
AB  - While the incidence of early-stage melanoma has dramatically increased over the
      past decades, the incidence and mortality rates of thick melanomas have remained
      relatively stable during the same period. A number of alternative theories have
      been postulated in order to explain these divergent trends between thin and thick
      melanomas, among which is the question of whether nodular melanoma may originate
      in the dermis. This concept has gained support from recent improvements in the
      understanding of the origin of melanocytes and the morphological and molecular
      diversity of melanoma. A dermal origin would plausibly explain why efforts at
      improving the early detection of melanoma largely fail, as it implies an
      initially intradermal growth that is hidden from our eyes until clinical signs
      and symptoms become only secondarily apparent. In light of this, at the current
      stage, the vision that no one should die of melanoma is an impossible mission.

PMID- 30190810
TI  - Combination therapies in advanced melanoma.
AB  - Until recently, melanoma represented a significant clinical challenge to
      oncologists. However, the approval in 2011 of ipilimumab, an anti-CTLA4
      monoclonal antibody, and vemurafenib, a BRAF inhibitor, completely changed
      melanoma management, with both drugs being shown to improve overall survival. The
      advent of these two drugs, together with the ongoing development of other
      targeted agents (e.g., MEK inhibitors) and immunotherapeutic compounds (e.g.,
      anti-PD-L1), is providing the opportunity to trial new combination or sequential
      therapy approaches. Combined approaches of these new agents with surgery,
      radiotherapy and/or chemotherapy are also being assessed. Targeted agents in
      combination or in sequence with new immunotherapeutic compounds may represent the
      future, not only for the treatment of melanoma, but also for the treatment of
      cancer in general.

PMID- 30190812
TI  - Towards skin cancer prevention and early detection: evolution of skin cancer
      awareness campaigns in Australia.
AB  - Since the 1980s, Australia's mass-media campaigns promoting skin cancer
      awareness, namely skin cancer-preventative behaviors and early detection, have
      targeted the general community as well as high-risk groups, including outdoor
      workers, schoolchildren and youths. During that time, campaigns have evolved in
      tone and method of delivery. Their messages are today accompanied by policies,
      supportive environments such as shade and access to quality sun-protection
      products governed by national standards. Early detection of skin cancer has been
      the other aim of these campaigns, and recent downturns in incidence rates,
      especially in the young, and the shift to mostly thin melanomas at diagnosis in
      Australia, may partly reflect some campaign success. However, sustained efforts
      are required for long-lasting skin cancer control.

PMID- 30190813
TI  - Management of 'pan-negative' melanoma: current and emerging strategies.

PMID- 30190814
TI  - Is vaccine research still relevant for metastatic melanoma?

PMID- 30190811
TI  - Melanoma and nuclear medicine.
AB  - Supported by a large body of published work, the contribution of nuclear medicine
      technologies to the assessment of melanoma has been increasing in recent years.
      Lymphoscintigraphy-assisted sentinel lymph node biopsy and PET are in continuous
      evolution with the aid of technological imaging advances, making it possible to
      fuse functional and anatomic images (e.g., with SPECT/CT, PET/CT and 3D rendering
      systems). The development of hybrid fluorescent-radioactive tracers that enable
      high-quality preoperative lymphoscintigraphy and SPECT/CT, and the optimization
      of modern intraoperative portable imaging technologies, such as free-hand SPECT
      and portable gamma-cameras, are important innovations that have improved sentinel
      lymph node identification in complex anatomical areas, such as the pelvis and
      head and neck. Concurrently, 18F-fluorodeoxyglucose-PET has proved its usefulness
      in the clinical staging and treatment decision-making process, and there is also
      emerging evidence regarding its utility in the evaluation of therapeutic
      response. The potential uses of other novel PET radiotracers could open up a new
      field of use for this technique. In this article, we review the current and
      future role of nuclear medicine in the management of melanoma.

PMID- 30190815
TI  - The impact of socioeconomic status on melanoma clinical trial participation: an
      observational cohort study from Australia.
AB  - Aim: This study aims to determine whether socioeconomic status (SES) is
      associated with participation in melanoma clinical trials. Patients & methods: A
      retrospective, single-center observational study was conducted at the Melanoma
      Institute Australia. Factors affecting clinical trial participation were assessed
      using logistic regression. Results: Of 9074 patients, 2304 (25%) participated in
      a clinical trial. Multivariate analysis indicated males compared with females
      (odds ratio [OR]: 1.18; 95% CI: 1.07-1.30) and patients with American Joint
      Cancer Committee stage II or III disease (but not stage IV disease) were more
      likely to participate in trials than patients with stage I disease (OR: 2.81 [95%
      CI: 2.50-3.16] and OR: 4.55 [95% CI: 3.91-5.30], respectively). SES did not
      affect trial participation. Conclusion: Our data suggest that SES is not a
      significant predictor of melanoma clinical trial participation when adjusted for
      other factors.

PMID- 30190816
TI  - Predicting melanoma risk: theory, practice and future challenges.
AB  - The incidence of melanoma continues to rise in most fair-skinned populations.
      Strategies to curb the toll from melanoma include targeting the patients who are
      at highest risk with the aim of either preventing the onset of cancer or
      intervening early in order to improve survival. The challenge has been to
      synthesize the available information on risk factors into prediction tools with
      clinical utility, such that 'high-risk' patients can be identified with accuracy.
      While a number of risk prediction tools for melanoma have been developed, few
      have undergone rigorous evaluation of their performance in order to assess
      calibration or discrimination, and even fewer have been validated in independent
      populations. Future research should assess the validity of existing tools and
      seek to integrate the increasing volumes of data being generated by genomic
      studies.

PMID- 30190817
TI  - Follow-up in patients with low-risk cutaneous melanoma: is it worth it?
AB  - Follow-up examinations in melanoma aim to detect recurrences or secondary
      melanomas in an early phase of development. Follow-up guidelines that have been
      developed in many European countries, the USA and Australia show varying
      recommendations and are controversial, especially in patients with melanomas of
      1.0 mm tumor thickness or less. This group contains 50-70% of all melanoma
      patients and the majority is unlikely to develop recurrences. On the other hand,
      within this entity, subgroups at higher risk for recurrences can be defined who
      require a more intense follow-up. This article discusses recommendations for the
      frequency, duration and costs of follow-up in low-risk melanoma patients. Patient
      preferences are addressed and a risk-adapted follow-up scheme is proposed.

PMID- 30190818
TI  - Induction of endoplasmic reticulum stress as a strategy for melanoma therapy: is
      there a future?
AB  - Melanoma cells employ several survival strategies, including induction of the
      unfolded protein response, which mediates resistance to endoplasmic reticulum
      (ER) stress-induced apoptosis. Activation of oncogenes specifically suppresses ER
      stress-induced apoptosis, while upregulation of ER chaperone proteins and
      antiapoptotic BCL-2 family members increases the protein folding capacity of the
      cell and the threshold for the induction of ER stress-induced apoptosis,
      respectively. Modulation of unfolded protein response signaling, inhibition of
      the protein folding machinery and/or active induction of ER stress may thus
      represent potential strategies for the therapeutic management of melanoma. To
      this aim, the present article focuses on the current understanding of how
      melanoma cells avoid or overcome ER stress-induced apoptosis, as well as
      therapeutic strategies through which to harness ER stress for therapeutic
      benefit.

PMID- 30190819
TI  - Biomarkers in melanoma: where are we now?
AB  - Melanoma has traditionally been associated with limited treatment options, and as
      such, biomarkers such as histopathologic staging and serum lactate dehydrogenase
      focused on prognosis. The development of effective treatment options shifted the
      search to biomarkers for predicting response and resistance to therapy, an
      arguably more critical goal. Specific genetic alterations (e.g., BRAFV600 and KIT
      mutations) predict response to molecularly targeted agents and are routinely used
      in clinical practice. Other promising biomarkers include T-cell characteristics
      (the circulating and tumor microenvironment), tumor expression of PD-L1,
      circulating DNA, circulating tumor cells and miRNAs. In this article, we discuss
      the status of the currently used and experimental tumor- and blood-based
      biomarkers for melanoma prognosis and response to targeted and immune therapies.

PMID- 30190822
TI  - The role of chemotherapy in the modern management of melanoma.
AB  - The last 4 years have seen dramatic changes in the treatment of advanced
      melanoma, largely based on advances in targeted therapy and immunotherapy. This
      article examines the role of chemotherapy in the modern management of melanoma.
      We examine the evidence for promising new agents and discuss their position in
      the sequencing of treatment options for patients with advanced disease. In
      addition, we discuss the combination of chemotherapy with targeted treatments and
      immune therapies. Finally, we discuss future areas of research for ensuring that
      we maximize the potential of all agents available to us and identify new,
      effective treatments.

PMID- 30190823
TI  - Barriers to risk-understanding and risk-reduction behaviors among individuals
      with a family history of melanoma.
AB  - Family members of melanoma patients are often called upon to provide support,
      ranging from monetary to medical assistance. Consanguineal relatives of melanoma
      patients are also at greater risk of developing the disease themselves. However,
      as a group, they have limited understanding of their melanoma risk and they
      demonstrate inadequate primary and secondary prevention behaviors. The optimal
      intervention strategies for improving the consistent use of such behaviors (i.e.,
      improving rates of sun-protection behaviors and screening) remains unclear,
      necessitating further research.

PMID- 30190821
TI  - How anti-PD1 treatments are changing the management of melanoma.
AB  - The introduction of immunotherapy based on the blockade of the PD1/PD-L1
      checkpoints has been associated with high response rates and durable remissions
      of disease in patients with metastatic melanoma, to the extent that it is now
      considered the standard of care for a wide range of patients, irrespective of
      their BRAF or NRAS mutation status. In addition, more frequent follow-up of
      patients who are at high risk of recurrence after surgical treatment appears to
      be justified, as does neoadjuvant treatments in order to render patients
      treatable by surgery. The limitations of this treatment include failure of some
      patients to respond, a low rate of complete responses and relapses of the disease
      during treatment. New initiatives in order to overcome these limitations include
      the identification of biomarkers for the selection responders and evaluations of
      treatment combinations that will increase responses and their durability. The
      latter includes combinations with antibodies against other checkpoints on T cells
      and cotreatments with inhibitors of resistance pathways in melanoma.

PMID- 30190824
TI  - Immunohistochemistry for an improved clinical workflow in the era of personalized
      melanoma therapy?

PMID- 30190820
TI  - Molecular pathology of cutaneous melanoma.
AB  - Cutaneous melanoma is associated with strong prognostic phenotypic features, such
      as gender, Breslow's thickness and ulceration, although the biological
      significance of these variables is largely unknown. It is likely that these
      features are surrogates of important biological events rather than directly
      promoting cutaneous melanoma progression. In this article, we address the
      molecular mechanisms that drive these phenotypic changes. Furthermore, we present
      a comprehensive overview of recurrent genetic abnormalities, both germline and
      somatic, in relation to cutaneous melanoma subtypes, ultraviolet exposure and
      anatomical localization, as well as pre-existing and targeted therapy-induced
      mutations that may contribute to resistance. The increasing knowledge of
      critically important oncogenes and tumor-suppressor genes is promoting a
      transition in melanoma diagnosis, in which single-gene testing will be replaced
      by multiplex and multidimensional analyses that combine classical
      histopathological characteristics with the molecular profile for the
      prognostication and selection of melanoma therapy.

PMID- 30190825
TI  - Combination approaches and anti-PD1 therapies: the focus of new research at ESMO
      and SMR.
AB  - Research into the treatment of melanoma is continuing to progress, and both the
      European Society of Medical Oncology (26-30 September, Madrid, Spain) and the
      Society of Melanoma Research (13-16 November, Zurich, Switzerland) 2014 annual
      meetings provided important updates in this field. Areas of particular focus
      included combinations of a BRAF inhibitor with a MEK inhibitor (COMBI-v and
      CoBRIM trials) and new data on anti-PD1 therapies (nivolumab and pembrolizumab).
      Overall, the data reported at these two meetings again suggest that melanoma is
      perhaps the most dynamic field of oncology, with continuing advances in
      management of the disease that may improve outcomes for patients in clinical
      practice.

PMID- 30190826
TI  - Synergistic effects of MAPK and immune checkpoint inhibitors in melanoma: what is
      the best combination strategy?

PMID- 30190827
TI  - Is histopathological overdiagnosis of melanoma a good insurance for the future?

PMID- 30190828
TI  - Electrochemotherapy: a good idea in recurrent basal cell carcinoma treatment.
AB  - Basal cell carcinoma (BCC) is the most common skin cancer in Caucasian
      population. Surgical excision is the gold standard treatment for BCC. Secondary
      surgical approach in patients presenting surgical scars after multiple surgical
      excisions or submitted to radiotherapy without obtaining a safe clearance margin,
      should be avoided. In recent years the use of electrochemotherapy (ECT) in head
      and neck cancers using intravenous bleomycin was specifically addressed and BCC
      resulted to be among tumors with the best response to ECT. We report a case of a
      recurrent nasal BCC treated with ECT with a complete regression of lesions after
      8 weeks and a disease free period of 7 months. ECT is a good palliative treatment
      not affecting survival rate but improving quality of life in patients.

PMID- 30190829
TI  - Ipilimumab for the treatment of melanoma.
AB  - Melanoma is the sixth most common cancer in the US. Metastatic melanoma has
      increased in incidence over the past 30 years. In the US approximately 8600
      people died from melanoma in 2009. It is an aggressive tumor; the prognosis of
      stage IV is poor. Before 2011, only dacarbazine and IL-2 were approved for
      metastatic melanoma. Major advances have been made in understanding the genetic
      profile, molecular factors that drive malignant transformation and the role of T
      cells in melanoma patients. Immune regulatory pathways affecting immune responses
      to cancer are becoming better defined. Cytotoxic T-lymphocyte-associated antigen
      4 (CTLA-4) downregulates the pathways of T-cell activation. Ipilimumab is an anti
      CTLA-4 monoclonal antibody approved in 2011 to treat metastatic or unresectable
      melanoma.

PMID- 30190830
TI  - Anti-PD1 and anti-PD-L1 in the treatment of metastatic melanoma.
AB  - Programmed cell death receptor-1 (PD-1) and programmed cell death-1 ligand-1 (PD
      L1) represent promising novel targets in immunotherapy. PD-1 is an inhibitory
      receptor involved in T-cell regulation that is expressed by activated T cells.
      Nivolumab and pembrolizumab are anti-PD-1 antibodies that have shown antitumor
      activity and acceptable tolerability in patients with metastatic melanoma in
      preclinical development and Phase I/II clinical trials. Several ongoing Phase III
      studies are further investigating the efficacy and safety of anti-PD-1 therapy in
      melanoma. Initial data on the combination of anti-PD-1 and anti-cytotoxic T
      lymphocyte-associated antigen 4 blockade with nivolumab and ipilimumab also
      appear promising. Monoclonal antibodies to blockade PD-L1 may also be an
      effective immunotherapy strategy in melanoma and several anti-PD-L1 antibodies
      are in development.

PMID- 30190833
TI  - Pharmacist's role in optimizing therapy of the newer agents for the treatment of
      metastatic melanoma.
AB  - Metastatic melanoma is a disease with a historically dismal survival of 6-9
      months with treatment. It is considered an incurable disease and resistant to
      conventional chemotherapy. We have learned much about the role of newer targets
      in the development of melanoma which has helped us in developing targeted therapy
      and improving immunotherapy for the treatment of melanoma. These new therapies
      have a different adverse event profile from conventional chemotherapy. We will
      define these and their management from the perspective of the oncology
      pharmacist. We will also discuss the role that the oncology pharmacist can play
      in optimizing therapy and side effect management in the multidisciplinary team
      treating patients that have unresectable or metastatic melanoma.

PMID- 30190831
TI  - Skin cancer and vitamin D: an update.
AB  - Exposure of the skin to solar ultraviolet (UV) radiation has both risks and
      benefits for human health. Absorption of UV-B radiation by DNA results in
      mutations that underlie the development of skin cancers, as is apparent from
      genetic studies showing high occurrence of UV signature mutations within these
      tumors. UV-B radiation is also absorbed by 7-dehydrocholesterol to initiate
      vitamin D synthesis. In experimental studies vitamin D metabolites enhance
      apoptosis of malignant cells, inhibit angiogenesis and proliferation and increase
      differentiation, potentially reducing skin cancer development and improving
      prognosis after diagnosis. There are some supporting human data. We review the
      links between sun exposure, vitamin D and skin cancers.

PMID- 30190832
TI  - Dermoscopy: not just for dermatologists.
AB  - Use of dermoscopy has been proven to increase diagnostic accuracy for melanoma.
      It is frequently used by dermatologists and other healthcare providers during
      skin cancer screening and in the evaluation of concerning skin lesions. Studies
      have shown that it is useful in the diagnosis of many nononcologic cutaneous
      diseases as well as in the monitoring of disease progression and treatment
      response. Furthermore, dermoscopy has the potential to aid in pathology specimen
      sectioning, translational research and medical technology development. Its broad
      applications and ease of use will make it an increasingly influential tool in
      healthcare. In this article, we review the established uses of dermoscopy by
      different healthcare providers and its potential future applications.

PMID- 30190834
TI  - Familial risk of melanoma and links with other cancers.
AB  - The genetic risk factors for melanoma are complex and involve both familial and
      environmental components. Of the thousands of melanomas diagnosed each year, only
      a fraction are due to familial causes. These melanomas typically present in
      younger individuals, and may be associated with genetic factors that put these
      individuals at risk for other tumors. CDKN2A and CDK4 are the most well
      characterized mutations, as they have been identified in up to 40% of familial
      melanomas. Individuals with CDKN2A are also at risk for pancreatic cancer. The
      BRCA2 mutation has also been implicated in familial melanomas, breast and ovarian
      cancer. The BAP1, TERC and POT1 mutations are associated with melanomas and
      several other familial tumors.

PMID- 30190835
TI  - Dynamic tumor heterogeneity in melanoma therapy: how do we address this in a
      novel model system?

PMID- 30190837
TI  - Rose Bengal for melanoma treatment: will it translate to the clinic?

PMID- 30190836
TI  - Melanomas' fatal attraction to lysophosphatidic acid trails: a new prognostic and
      therapeutic approach?

PMID- 30190838
TI  - Oncolytics Biotech(r) Inc.: REOLYSIN(r) for melanoma therapy.
AB  - Oncolytics Biotech(r) Inc. is focused on the development of oncolytic viruses for
      use as cancer therapeutics. The Company's lead product, REOLYSIN(r), a
      proprietary formulation of the human reovirus, is in late-stage clinical testing
      in a range of cancers. REOLYSIN has been utilized in nearly 30 clinical trials
      including translational, Phase I, Phase II (single arm and randomized) and Phase
      III studies in a broad range of cancer indications. To date, Oncolytics has been
      issued more than 370 patents worldwide and has more than 230 pending
      applications. Issued patent claims pertaining to the reovirus cover: compositions
      of matter comprising reovirus; pharmaceutical use of reoviruses to treat
      neoplasia and cellular proliferative diseases and combination therapy with
      radiation, chemotherapy and/or immune suppressants.

PMID- 30190839
TI  - Melanoma initiating cells: where do we stand?

PMID- 30190840
TI  - Bowel perforation associated with robust response to BRAF/MEK inhibitor therapy
      for BRAF-mutant melanoma: a case report.
AB  - Combination BRAF/MEK inhibition has shown improved response rates and longer
      progression-free and overall survival for patients with BRAF-mutant metastatic
      melanoma. A 63-year-old female with widely metastatic BRAF V600E-mutant melanoma
      was treated with dabrafenib/trametinib. Ten weeks into therapy, she was treated
      conservatively for a partial bowel obstruction involving a lesion in the distal
      ileum. She presented two weeks later with CT evidence of a high-grade bowel
      obstruction with perforation. Emergent surgery was performed. Intraoperative
      inspection and pathologic analysis of the resected specimen revealed no evidence
      of melanoma. Seven months postoperatively she is disease free and fully
      functional. Rapid BRAF/MEK inhibitor-induced regression of small bowel lesions
      can result in bowel perforation, which is critical to distinguish from the
      consequences of disease progression.

PMID- 30190841
TI  - Spitzoid melanoma of childhood: a case series and review.
AB  - Spitzoid melanomas (SM) and atypical Spitz tumors (AST) are rare pediatric
      neoplasms. We performed a retrospective, single-institution review and report our
      institutional experience. We identified 10 patients (median age: 12.5 years). A
      sentinel node biopsy (SNB) was performed in 8/10 (80%) patients, and
      interestingly 7/8 (87.5%) were found to be positive for malignant cells. A
      complete regional lymphadenectomy was performed in all SNB-positive patients, but
      only 2/8 (25%) were found to have additional lymph node spread. Adjuvant therapy
      was administered in 5/8 SLNB-positive and 2/2 (100%) regional LN-positive cases.
      All patients had excellent long-term outcomes (100% survival). This report
      highlights the excellent outcomes associated with SNB + pediatric SM and AST.

PMID- 30190842
TI  - Electrochemotherapy in melanoma patients: a single institution experience.
AB  - Aim: This study was undertaken to update the outcome of the treated lesions with
      electrochemotherapy (ECT) plus intravenous injection of bleomycin in patients
      with in-transit disease or distant cutaneous metastases in melanoma patients.
      Patients & methods: 89 patients with relapsed and refractory cutaneous melanoma
      metastases or in-transit disease were submitted to 126 treatments of ECT.
      Results: 34 patients (38.2%) had a partial response and 43 had a complete
      response (48.3%). 12 patients (13.5%) had no change or progressive disease. The
      objective response rate was 67.5%. Conclusion: The favorable outcome obtained in
      the present study demonstrates that ECT is a reliable, easy, fast and effective
      procedure showing benefits in terms of curative and palliative treatment for
      unresectable cutaneous lesions respecting the quality of life.

PMID- 30190845
TI  - Genetic epidemiology of malignant melanoma susceptibility.
AB  - Germline CDKN2A mutations were the first to be associated with familial melanoma.
      MC1R polymorphisms are associated, in conformity with epidemiological
      observations, with fair skin phenotype and a moderately increased risk for
      melanoma. The wider implementation of genome-wide association studies along with
      improved whole exome sequencing techniques made possible the identification of
      novel high-penetrant mutations (TERT, MITF, POT1, BAP1) beyond the established
      pathways of pigmentation and nevus count suggesting an additional role for
      pathways involved in cell cycle control and DNA repair. A multitude of common
      polymorphisms in the general population have been associated through candidate
      gene studies with a low risk for melanoma, supporting the hypothesis of a complex
      disease.

PMID- 30190844
TI  - Epidemiological and genetic factors underlying melanoma development in Italy.
AB  - Among human cancers, melanoma remains one of the malignancies with an ever
      growing incidence in white populations. Recent advances in biological and
      immunological therapeutic approaches as well as increased efforts for secondary
      prevention are contributing to improve the survival rates. It is likely that a
      significant fall in mortality rates for melanoma will be achieved by further
      increase of the early detection through a more accurate selection of the higher
      risk individuals (i.e., carriers of predisposing genetic alterations). A similar
      scenario occurs in Italy. In the present review, we have considered data on
      incidence, survival and mortality rates of melanoma in Italian population,
      including evaluation of the main risk factors and genetic mutations underlying
      disease susceptibility.

PMID- 30190843
TI  - Oncogene-directed small molecule inhibitors for the treatment of cutaneous
      melanoma.
AB  - Achievements in cancer genetics and molecular biology have revolutionized the
      treatment options available for advanced melanoma. Patients with certain
      molecularly defined melanomas have been the most fortunate beneficiaries of
      recently US FDA-approved therapies that target aberrant MAPK pathway signaling,
      yet response rates and duration of response remain suboptimal. Furthermore, many
      patients harbor melanomas for which no approved targeted therapies currently
      exist. Since the approval of vemurafenib, a selective BRAF V600E inhibitor, in
      2011, there has been a surge of preclinical and clinical studies aimed at
      developing novel targeted therapies for a wide range of molecularly defined
      melanomas. In this review, we will examine the present status and future
      potential of molecularly targeted therapies directed at the most significant
      oncogenic signaling pathways in melanoma.

PMID- 30190846
TI  - Lentigo maligna and lentigo maligna melanoma: contemporary issues in diagnosis
      and management.
AB  - Lentigo maligna and lentigo maligna melanomas present diagnostic and treatment
      dilemmas due to their frequent presence within a background of sun-damaged skin,
      and their location on cosmetically and functionally sensitive areas. As the
      incidence of this entity is increasing, diagnostic and management controversies
      have developed. While surgery remains the gold standard of treatment, nonsurgical
      treatment options are also emerging for both adjunctive and primary therapy.

PMID- 30190847
TI  - En1 fibroblasts and melanoma.

PMID- 30190848
TI  - From personalized to patient-specific treatment of metastatic melanoma.

PMID- 30190849
TI  - Dabrafenib and its use in the treatment of metastatic melanoma.
AB  - Approximately 50% of melanomas have mutations in the gene encoding BRAF. In
      recent years, new targeted therapies have transformed the landscape of metastatic
      melanoma treatment. Dabrafenib, a potent kinase inhibitor of mutated BRAF, has
      been showed to have high response rates with a rapid onset of response, as well
      as improved overall and progression-free survival when compared with
      chemotherapy. Dabrafenib in combination with trametinib, a MEK inhibitor, has
      demonstrated higher responses and improved clinical efficacy compared with
      monotherapy. Toxicity is distinct compared with chemotherapy but manageable. This
      article summarizes the pharmacology, key clinical trial data as well as practical
      experience with dabrafenib in clinical practice, and future directions.

PMID- 30190850
TI  - Vemurafenib plus cobimetinib in the treatment of mutated metastatic melanoma: the
      CoBRIM trial.
AB  - The concomitant inhibition of both BRAF and MEK can produce a more durable and
      greater tumor response than BRAF monotherapy while reducing BRAF inhibitor
      related toxicity. Further evidence of the benefits of combined MEK and BRAF
      inhibition have been provided by the CoBRIM trial in which median progression
      free survival was significantly increased with vemurafenib plus cobimetinib
      compared with vemurafenib alone (9.9 vs 6.2 months; hazard ratio for death or
      progression: 0.51; 95% CI: 0.39-0.68; p < 0.001) in 495 patients with advanced
      BRAF-mutated melanoma. Overall survival data in the CoBRIM trial were immature at
      time of final progression-free survival analysis but showed an hazard ratio for
      death of 0.65 (95% CI: 0.42-1.00; p = 0.046; boundary p < 0.0000037). Combination
      therapy was well tolerated with a reduced incidence of cutaneous squamous-cell
      carcinoma/keratoacanthoma. This combination may be a starting point for novel
      combination strategies with immunotherapies and other targeted therapies.

PMID- 30190851
TI  - Predicting the outcome of melanoma: can we tell the future of a patient's
      melanoma?
AB  - Cutaneous melanoma is responsible for the greatest number of skin cancer related
      deaths. For many years there were few therapeutic options. However, in the last
      years a number of new therapeutic options have emerged showing improved survival
      rates for advanced melanoma patients. A significant question based on these
      findings is whether identification and treatment of patients with biologically
      aggressive melanomas at an earlier clinical stage offer an opportunity for even
      greater improvement in overall survival. In this review, we will discuss the
      recent advancements in molecular strategies beyond traditional staging to
      identify biologically aggressive melanomas, and which are their implications in
      terms of predicting the prognosis of patients with melanoma.

PMID- 30190852
TI  - Management of melanoma brain metastases.
AB  - Relapses in the brain remain a major obstacle to cure in many patients with
      advanced melanoma. At present, the management of melanoma brain metastases
      continues to rely heavily on surgical and radiotherapeutic interventions, which
      have become safer and more effective with modern imaging, surgery and radiation
      technologies. Additionally, novel targeted and immunotherapeutic agents, shown to
      generate meaningful intracranial response and survival benefit in patients with
      melanoma brain metastases when compared with historical controls, expand systemic
      treatment options for this subset of patients. These systemic therapies become
      particularly important when intracranial disease burden precludes neuro- or radio
      surgery. Considerable multidisciplinary research effort is ongoing to improve
      outcomes for melanoma patients with brain metastases, a key challenge in the
      management of advanced melanoma.

PMID- 30190853
TI  - CDK4 inhibitors an emerging strategy for the treatment of melanoma.
AB  - Research into the cyclin-dependent kinases and their inhibitors is finally coming
      into the forefront of clinical research in cancer. Targeted therapies such as
      BRAF inhibitors have led the way in improving treatment outcomes in advanced
      melanoma. Based on detailed genomic knowledge of melanoma it is now time to
      extend targeted therapies beyond BRAF to fulfill the vision of precision
      medicine. The p16INK4A-cyclin D-CDK4/6-retinoblastoma protein pathway (RB
      pathway) is dysregulated in more than 90% of melanomas and interacts
      biochemically and genetically with the RAS/RAF/MEK/ERK pathway. Recognizing and
      understanding these processes that drive melanomagenesis is essential to
      rationally develop new therapies. This paper reviews the mechanisms, background
      and progress of small molecule CDK4 inhibitors in the management of melanoma.

PMID- 30190856
TI  - Intratumoral talimogene laherparepvec therapy in melanoma.

PMID- 30190855
TI  - Analysis of melanoma recurrence following a negative sentinel lymph node biopsy.
AB  - Little attention has been paid to the characteristics and outcomes of patients
      who experience distant, local or regional recurrence of melanoma following a
      negative sentinel lymph node biopsy. This article aims to review the published
      literature on the topic and presents some general summaries regarding this
      patient population. Patients who experience a disease recurrence following a
      negative sentinel lymph node biopsy have a worse overall survival compared with
      patients with a positive sentinel lymph node biopsy. The implications and
      possible explanations for these findings are discussed in order to both
      underscore the need for in-depth investigation of local, regional or distant
      melanoma recurrence among patients following a true negative sentinel lymph node
      biopsy, as well as increased efforts to minimize the rate of false negative
      sentinel lymph node biopsies.

PMID- 30190857
TI  - Surgical management of malignant melanoma of the lung.

PMID- 30190858
TI  - The end of the beginning: PD-1 inhibition as the new standard of care first-line
      immunotherapy in metastatic melanoma.

PMID- 30190854
TI  - Immune checkpoint inhibitors in melanoma.
AB  - The potential to harness the power of the immune system and effectively treat
      patients with metastatic melanoma is finally being realized with the advent of
      immune checkpoint inhibitors. These new therapies herald a new era in the
      treatment of melanoma with the potential to produce very durable responses and
      possible cure for a subset of patients, though bring with them challenges
      including novel toxicities and nonconventional response patterns. This article
      reviews the currently available immune checkpoint inhibitors, potential
      biomarkers to predict response and promising investigational approaches including
      combination therapies.

PMID- 30190859
TI  - Report of ipilimumab in a heart transplant patient with metastatic melanoma on
      tacrolimus.
AB  - Ipilimumab is the first immunotherapy shown to increase overall survival in
      patients with metastatic melanoma. Currently, there are no accepted guidelines
      for use of ipilimumab in organ transplant patients. There is only one report in
      the literature on successful administration of ipilimumab in two kidney
      transplant recipients. In this report, a heart transplant patient with metastatic
      melanoma was successfully treated with ipilimumab. He experienced no adverse drug
      reactions. However, after standard treatment with regimen of four doses at 3
      mg/kg, he experienced disease progression. Here, we address concerns of organ
      rejection or ineffective treatment when using ipilimumab or other immune
      checkpoint inhibitors in patients who are chronically immunosuppressed.

PMID- 30190860
TI  - Pembrolizumab in the management of metastatic melanoma.
AB  - Pembrolizumab is a humanized IgG4 anti-PD-1 antibody that plays a major role in
      the treatment of advanced melanoma. Through blockade of PD-1, it leads to an
      increase in effector T-cell activity in the tumor microenvironment. Clinical
      trial outcomes for pembrolizumab in addition to pharmacokinetics,
      pharmacodynamics and safety of the compound are discussed in this article. Phase
      I trials have demonstrated safety and efficacy of pembrolizumab in advanced,
      pretreated melanoma patients. When compared with chemotherapy in a Phase II trial
      of ipilimumab-refractory patients, those treated with pembrolizumab showed
      superior progression-free survival. In addition, in the pivotal Phase III trial
      pembrolizumab improved overall survival compared with ipilimumab in patients
      naive to immune checkpoint inhibition. Pembrolizumab is well tolerated and has a
      favorable safety profile. Common adverse events are fatigue, rash, itching and
      diarrhea. Less frequent immune-related adverse events include hypothyroidism,
      colitis, hepatitis and pneumonitis.

PMID- 30190861
TI  - Conceptual approach to early melanoma detection: models, tools, issues and
      challenges.
AB  - Identification and removal of melanoma early in its development remains the most
      effective treatment. However, identification of early melanoma remains
      challenging and may result in unnecessary morbidity due to the excess excision of
      benign melanocytic nevi. Herein, we present a conceptual model of benign and
      malignant melanocytic growths. The potential differences in the location of the
      cell of origin as well as considerations for neoplasm progression are also
      reviewed. Several of the clinical tools currently available, the integration of
      information from those different sources, and approaches to set an optimum biopsy
      threshold are discussed. While early detection remains a challenge, significant
      progress has been made. Insight into melanoma growth processes and appropriate
      use of available tools can result in the detection of thinner melanomas while
      also decreasing overall biopsy rates.

PMID- 30190862
TI  - Targeting immune checkpoints in melanoma: an update.
AB  - Different treatment modalities encompassed under the term 'immunotherapy' have
      led to major breakthroughs in the treatment of melanoma. Immune checkpoint
      blocking antibodies targeting CTLA-4 and PD-1 result in significant activity and
      prolonged survival in patients with advanced melanoma and are currently available
      for clinical use. Studies addressing novel immune checkpoint blocking antibodies,
      combined approaches and predictive/prognostic biomarkers are expected to broaden
      the applicability and efficacy of this approach. In this article, we will review
      clinically meaningful aspects of immune checkpoint blockade, promising strategies
      under development and the challenges faced in a continuous search to improve the
      outcomes of patients affected by this disease.

PMID- 30190863
TI  - The potential complementary role of targeted alpha therapy in the management of
      metastatic melanoma.
AB  - Standard treatments for metastatic melanoma have recently extended survival
      although many patients still succumb. Targeted alpha therapy (TAT) is a new
      therapeutic approach in which a cancer-targeting vector is labeled with an alpha
      emitting radioisotope. Alpha-particles have the shortest range and highest energy
      transfer, and produce localized, high-density and lethal ionization damage to
      DNA. Thus, the targeted radiation can kill isolated cancer cells circulating in
      blood and lymphatic vessels, regress metastatic cancer cell clusters, and disrupt
      the vasculature of solid tumors. Preclinical and clinical studies of TAT for
      metastatic melanoma demonstrate its safety and anti-tumor activity. We recommend
      ways in which TAT can be used to treat small-volume disease sometimes in
      conjunction with cytoreductive anti-melanoma therapies.

PMID- 30190866
TI  - Can histone proteins promote the growth of melanoma?

PMID- 30190865
TI  - The digital age of melanoma management: detection and diagnostics.
AB  - New technologies are increasingly impacting the way melanoma is detected and
      diagnosed. Devices, software and diagnostics abound, ranging from smartphone
      applications that purport to predict which lesions are likely to be malignant, to
      genomic analysis of low-stage melanomas to predict metastatic risk. The purpose
      of this review is to concisely update practitioners on the research behind the
      latest tools available for melanoma detection and diagnosis, as well as the
      implications of these technologies for melanoma management.

PMID- 30190867
TI  - What are the therapeutic implications of increased collagen expression in
      melanoma cells treated with vemurafenib?

PMID- 30190868
TI  - Emerging immune therapy of metastatic melanoma in the older patient: does age
      really matter?

PMID- 30190864
TI  - Epigenetic markers in melanoma.
AB  - Melanoma, one of the most virulent forms of human malignancy, is the primary
      cause of mortality from cancers arising from the skin. The prognosis of
      metastatic melanoma remains dismal despite targeted therapeutic regimens that
      exploit our growing understanding of cancer immunology and genetic mutations that
      drive oncogenic cell signaling pathways in cancer. Epigenetic mechanisms,
      including DNA methylation/demethylation, histone modifications and noncoding RNAs
      recently have been shown to play critical roles in melanoma pathogenesis. Current
      evidence indicates that imbalance of DNA methylation and demethylation,
      dysregulation of histone modification and chromatin remodeling, and altered
      translational control by noncoding RNAs contribute to melanoma tumorigenesis.
      Here, we summarize the most recent insights relating to epigenetic markers,
      focusing on diagnostic potential as well as novel therapeutic approaches for more
      effective treatment of advanced melanoma.

PMID- 30190869
TI  - Low-dose brachytherapy strategies to treat uveal melanoma: is less more?
AB  - The Collaborative Ocular Melanoma Study (COMS) has established equivalency of
      globe salvaging brachytherapy compared with enucleation in terms of survival for
      medium-sized choroidal melanoma. The radiation dose protocol followed by the COMS
      was 85 Gray to a prescription point of the tumor apex or 5 mm inner sclera;
      whichever was greater. While the COMS realized appropriate local and distant
      tumor control rates, ocular morbidity due to radiation complications remains a
      significant clinical challenge. Recent studies challenge the COMS radiation dose
      paradigm by demonstrating similar tumor control by utilizing lower radiation
      doses that are associated with reduced radiation toxicity. Improved operative
      techniques including intraoperative ultrasound can aid to obtain adequate
      radiation delivery to the tumor by ensuring optimal plaque position. Adjuvant
      transpupillary thermotherapy, intravitreal anti-VEGF and posterior sub-Tenon
      steroids may further enhance outcome by providing additional tumor control and/or
      facilitating visual recovery.

PMID- 30190870
TI  - The role of tumor microenvironment in melanoma therapy resistance.
AB  - Melanoma patients develop resistance to both chemotherapy and targeted-therapy
      drugs. Promising preclinical and clinical results with immune checkpoint
      inhibitors using antibodies directed against cytotoxic T-lymphocyte-associated
      protein 4 and programmed cell death protein 1 have re-energized the field of
      immune-based therapies in melanoma. However, similar to chemotherapy or targeted
      therapies, immune checkpoint blockade responds in only subsets of melanoma
      patients. A number of factors, including gene mutations, altered cell-signaling
      pathways and tumor heterogeneity can contribute to therapy resistance. Recent
      studies have highlighted the role of inflammatory tumor microenvironment on
      therapy resistance of cancer cells. Cancer cells either alone or in conjunction
      with the tumor stroma can contribute to an inflammatory microenvironment.
      Multimodal approaches of targeting the tumor microenvironment, in addition to
      malignant cells, may be necessary for better therapy responses.

PMID- 30190874
TI  - Lymph nodes and the melanoma surgeon: re-defining a long-term relationship.
AB  - Surgeons now have an enhanced ability to stage patients with clinically localized
      cutaneous melanoma using sentinel lymph node biopsy. Despite this, the weight of
      clinical evidence is tilting in favor of a measured approach to pre-emptive lymph
      node removal. Careful consideration of whether traditional surgical approaches to
      the regional nodes, whether done in the name of 'staging' or pre-emptive removal
      of a potential site of relapse, really 'benefit' the patient is paramount for
      optimal care.

PMID- 30190871
TI  - Biology and treatment of BRAF mutant metastatic melanoma.
AB  - BRAF inhibitors were among the first systemic therapies to show clinical benefit
      in metastatic melanoma. Here, we review the spectrum of BRAF mutations in
      melanoma, their role in oncogenesis, clinicopathological associations and
      response to treatment. The differing biology and clinical features of V600E- and
      V600K-mutated melanoma are outlined. The molecular changes associated with BRAF
      fusion genes and their response to targeted therapies, as well as the role of
      immunotherapy in treatment sequencing with targeted therapies are discussed.

PMID- 30190872
TI  - NRAS mutant melanoma: an overview for the clinician for melanoma management.
AB  - Melanoma is the deadliest form of skin cancer and the incidence continues to rise
      in the United States and worldwide. Activating mutations in RAS oncogenes are
      found in roughly a third of all human cancers. Mutations in NRAS occur in
      approximately a fifth of cutaneous melanomas and are associated with aggressive
      clinical behavior. Cells harboring oncogenic NRAS mutations exhibit activation of
      multiple signaling cascades, including PI3K/Akt, MEK-ERK and RAL, which
      collectively stimulate cancer growth. While strategies to target N-Ras itself
      have proven ineffective, targeting one or more N-Ras effector pathways has shown
      promise in preclinical models. Despite promising preclinical data, current
      therapies for NRAS mutant melanoma remain limited. Immune checkpoint inhibitors
      and targeted therapies for BRAF mutant melanoma are transforming the treatment of
      metastatic melanoma, but the ideal treatment for NRAS mutant melanoma remains
      unknown. Improved understanding of NRAS mutant melanoma and relevant N-Ras
      effector signaling modules will be essential to develop new treatment strategies.

PMID- 30190873
TI  - The role of radiation therapy in the management of cutaneous melanoma.
AB  - The local treatment of cutaneous melanoma with surgical excision is well
      established; however, the role of adjuvant radiation is not well-defined.
      Characteristics of the primary melanoma can indicate a higher local recurrence
      risk and thus warrant consideration of adjuvant treatment to the primary site.
      Management of the lymph node regions has been studied in some recent clinical
      trials, especially with the advent of sentinel lymph node procedures. We will
      review the indications for radiation to the primary site as well as lymph node
      regions based on the available data.

PMID- 30190875
TI  - Does an increased number of moles correlate to a higher risk of melanoma?

PMID- 30190876
TI  - Indoor tanning and melanoma: are gay and bisexual men more at risk?

PMID- 30190877
TI  - Nevisense: improving the accuracy of diagnosing melanoma.

PMID- 30190878
TI  - Repeat courses of SRS in patients initially treated with SRS alone for brain
      metastatic melanoma.
AB  - Aim: Stereotactic radiosurgery (SRS) is often used in the treatment of brain
      metastatic melanoma. Little data exist regarding outcomes of repeat course of SRS
      in this population. We aimed to identify treatment outcomes and toxicities in
      melanoma patients treated with repeat SRS after upfront SRS. Patients & methods:
      We reviewed ten consecutive patients treated with repeat SRS following upfront
      SRS alone for brain metastatic melanoma. Results: The median overall survival
      from initial treatment was 17.5 months. The median overall survival from repeat
      SRS was 6.7 months with a 6-month local control rate of 80%. The majority of
      patients progressed systemically before death. Four patients reported six adverse
      events, all grade 1. Conclusion: Prospective study regarding the safety and
      efficacy of repeat courses of SRS in patients with brain-metastatic melanoma,
      especially in combination with novel immunotherapies, is warranted.

PMID- 30190879
TI  - Patterns and sources of information about family melanoma risk among melanoma
      survivors.
AB  - Aim: Melanoma survivors can play a pivotal role in raising family melanoma risk
      awareness, but are not always aware of family risk. This study examines patterns
      and sources of survivors' awareness that first-degree relatives (FDRs) face
      heightened melanoma risk. Patients & methods: Population-based melanoma survivors
      (n = 170) completed a 15-min telephone interview. Logistic regressions examining
      covariates were conducted using awareness (yes vs no) of heightened risk to FDRs
      as the dependent variable. Results: Almost half (41%) were unaware that their
      FDRs faced heightened melanoma risk. Of those 59% who were aware, most learned
      this from dermatologists. In multivariable analyses perceived risk and body site
      remained significant. Conclusion: Many melanoma survivors remain unaware that
      their FDRs are at melanoma risk. The results underscore the role that
      dermatologists and other doctors play in fostering risk awareness. Sensitivity to
      providing family risk information to survivors who have lower risk perceptions,
      regardless of anatomic site, is warranted.

PMID- 30190880
TI  - Intralesional treatment for advanced melanoma: what's on the horizon?
AB  - Advances in treatment of melanoma with systemic immunotherapies continue, with
      promising findings for anti-PD-1 agents combined with ipilimumab. Still, an unmet
      need persists because of populations ineligible for systemic immunotherapies,
      incomplete cure/response rates, toxicities and extreme costs. Also, potential for
      effective use of intralesional therapies remains, especially for local regional
      disease, but also for benefits of local ablation and adjuvant systemic host tumor
      specific responses. Clinical trials of T-VEC, PV-10, CAVATAK and electroporation
      with plasmid IL-12 have demonstrated favorable, durable responses. Initial
      experience combining T-VEC, the agent furthest along in testing, with ipilimumab
      revealed higher complete and overall response rates than with either agent alone.
      Intralesional therapies may offer a treatment tool in the growing therapeutic
      armamentarium against this lethal disease.

PMID- 30190881
TI  - Immunotherapy for uveal melanoma.
AB  - Uveal melanoma (UM) is a rare cancer with a high mortality rate. In comparison to
      cutaneous melanoma, UM has unique immunological features. Arising in the immune
      suppressive environment of the eye, it maintains immune resistance once
      metastatic. This is considered a major obstacle for successful immunotherapy in
      UM. However, a growing body of evidence suggests strategies that may abrogate
      resistance and enhance antitumor immunity in UM. Recently, three new immune
      agents have been approved for melanoma. While these drugs demonstrate durable
      clinical responses with long-term remissions in metastatic cutaneous melanoma,
      only limited data exist in metastatic UM. In this review, immunological aspects
      of UM and data from clinical studies of immunotherapeutic agents and regimens for
      UM will be discussed.

PMID- 30190884
TI  - Pin1-FOXM1 inhibitors: a potential therapeutic for metastatic melanoma?

PMID- 30190882
TI  - Adjuvant treatment for stage III melanoma in the era of targeted medicine and
      immunotherapy.
AB  - The accelerated development in the treatment of metastatic melanoma, both in
      molecular targeted therapy and immunotherapy, is already starting to impact on
      adjuvant therapy in stage III melanoma. Following the approval of ipilimumab for
      adjuvant therapy in melanoma, clinical trials assessing other checkpoint
      modulators and MAPK pathway inhibitors as adjuvant treatments for melanoma are
      currently ongoing. As results from these trials mature in the next few years, a
      change in the landscape of adjuvant treatment for melanoma is expected, resulting
      in new challenges in treatment decisions such as optimizing patients selection
      through predictive and prognostic biomarkers, and management of treatment related
      adverse events, in particular immune related toxicities.

PMID- 30190883
TI  - Neoadjuvant treatment for melanoma: current challenges and future perspectives.
AB  - There will be an estimated 76,100 new cases of melanoma diagnosed in 2015 and
      9710 deaths. Patients with stage I/II disease have excellent outcomes, and the
      treatment landscape for patients with metastatic disease has been transformed by
      the approval of several immune checkpoint inhibitors and molecular targeted
      therapies. Patients with stage III disease, however, continue to have very
      limited options, as the only agent shown to improve survival in the adjuvant
      setting is high-dose IFN-alpha. Neoadjuvant trials of chemotherapy and
      chemobiotherapy have not been successful, and while neoadjuvant ipilimumab and
      high-dose interferon have shown promise in small trials, neither agent has been
      approved. Current trials are testing immune therapy and targeted therapy
      combinations in the neoadjuvant setting.

PMID- 30190885
TI  - 40 years in melanoma research: an interview with Meenhard Herlyn about his career
      in research and the outlook for the field.
AB  - Meenhard Herlyn speaks to Sebastian Dennis-Beron, Commissioning Editor: Dr
      Meenhard Herlyn is Caspar Wistar Professor for Melanoma Research and Director of
      the Melanoma Research Center at The Wistar Institute in Philadelphia, as well as
      Founding President of the Society for Melanoma Research. He has been a cancer
      researcher since arriving at Wistar in 1976 and has worked in melanoma research
      since 1977. Current major efforts include the ability to model the
      microenvironment of normal and diseased human tissue through 3D artificial skin,
      providing his laboratory with a unique insight into cancer research. His
      laboratory also seeks to further define the various signaling pathways that work
      in cancer cells in order to discover new opportunities to inhibit cancer growth
      through targeted therapeutics. Since therapy is increasingly guided by the
      genetic aberrations in tumors, Dr Herlyn and colleagues are developing
      combinations of compounds that take into account the genetic signature of tumors,
      with the specific goal of individualized cancer therapy. Another major effort of
      his laboratory is the study of therapy resistance and tumor dormancy. Tumor cells
      can become dormant in primary tumors or at any time after metastatic
      dissemination and can persist in the dormant state for many years, allowing
      tumors to resist treatment. Dr Herlyn's working hypothesis is that defined tumor
      subpopulations are central to dormancy and drug resistance due to their slow
      turnover and their nonresponsiveness to growth signals. His efforts seek to
      define how tumor cells escape dormancy for growth, invasion and metastasis, and
      how to best develop strategies for therapy. Because of the significance of
      immunotherapy in treatment of melanoma patients, the laboratory has developed two
      models that closely mimic the conditions in humans with the ultimate goal of
      combining targeted and immune therapies.

PMID- 30190886
TI  - Advancements in unresectable melanoma: a multidisciplinary perspective.

PMID- 30190887
TI  - Outcomes and toxicity of stereotactic radiosurgery for melanoma brain metastases
      in patients receiving ipilimumab.
AB  - Purpose: Patients with melanoma treated with ipilimumab and radiosurgery
      (stereotactic radiosurgery [SRS]) were reviewed for efficacy/safety. Methods:
      Patients who received ipilimumab and SRS for brain metastases were analyzed for
      control of SRS-treated metastasis and overall survival. Results: We identified 27
      patients, 26 were assessable for outcomes. Median time-to-treated metastasis
      progression was 6.3 months (95% CI: 3.1-12.2). Overall survival was 23.4 months
      (95% CI: 5.7-not estimable) for SRS prior to/during ipilimumab (n = 14), and 10.4
      months (95% CI: 1.9-not estimable) for SRS after ipilimumab (n = 12). Overall, no
      unexpected toxicities were seen: 11% of patients experienced grade 3 CNS toxicity
      and 7% developed radionecrosis. Conclusion: SRS for melanoma brain metastases
      with ipilimumab was well-tolerated. There may be improved survival for patients
      receiving SRS prior to/during ipilimumab.

PMID- 30190888
TI  - PD-L1 in melanoma: facts and myths.
AB  - The use of monoclonal antibodies that block immunologic checkpoints that would
      otherwise mediate the adaptive immune resistance have paved the way in cancer
      treatment. There is evidence that blocking the PD-1/PD-L1 axis is a strategy of
      overriding importance in the treatment of patients with metastatic melanoma and
      other solid malignancies, some of which (NSCLC, colorectal cancer, renal cell
      cancer, head and neck cancer) were not considered to be 'immune-responsive'
      diseases until recently. In this perspective article, the biological and clinical
      relevance of PD-L1 is summarized in the context of the immune checkpoint
      inhibitors as a therapeutic strategy in metastatic melanoma patients.

PMID- 30190889
TI  - New insights in melanoma biomarkers: long-noncoding RNAs.
AB  - Melanoma is one of the leading cancers worldwide, distinguished for its
      malignancy and low survival rates. Although the poor outcome could improve with
      an early diagnosis and a good monitoring of the disease, current melanoma
      biomarkers display several limitations which make them useless. Interestingly,
      long-noncoding RNAs are secreted into the bloodstream inside exosomes by a wide
      range of malignant cells, and several of them have been validated as promising
      circulating molecular signatures of other tumors, but not melanoma. In this
      review we propose to explore the booming field of long-noncoding RNAs in order to
      find potential candidates to be tested as novel melanoma biomarkers, with the
      ultimate goal of improving melanoma detection, diagnosis and prognosis.

PMID- 30190891
TI  - The cutting edge of metastatic melanoma therapy.
AB  - The past decade has witnessed impressive new developments for the treatment of
      melanoma. The discovery of key oncogenic driver mutations, upon which tumor
      establishment and progression are dependent, changed the prognosis of patients
      with stage IV disease. Extensive preclinical and clinical studies have shown high
      response rates and survival benefits over conventional chemotherapies provided by
      target-specific inhibitors of BRAF- or NRAS-activating mutations. Recent genomic
      analyses of melanoma have also given new potentially targetable driver mutations.
      In addition, the quickened pace of development of immune checkpoint inhibitors
      for the treatment of melanoma offers the unique opportunity to provide a long
      term clinical benefit. In this emerging era, predictive biomarkers for the
      selection of patients are required to help us develop an optimal therapeutic
      strategy.

PMID- 30190890
TI  - Copper suppression as cancer therapy: the rationale for copper chelating agents
      in BRAFV600 mutated melanoma.
AB  - The successful targeting of oncogenic BRAFV600 represents one of the landmark
      breakthroughs in therapy for advanced melanoma. While the initial clinical
      benefit can be dramatic, resistance is common due to a number of mechanisms,
      including MAPK pathway reactivation. Recent data have revealed a novel role for
      copper (Cu) in BRAF signaling with potential clinical implications. The history,
      preclinical data and efficacy of Cu chelating agents in cancer, specifically
      tetrathiomolybdate, will be reviewed with a focus on the rationale for targeting
      the MAPK cascade in melanoma through novel combination strategies.

PMID- 30190893
TI  - Melanoma vaccines and viral-based immunotherapies: a special focus issue from
      Melanoma Management.

PMID- 30190892
TI  - Combination or single-agent ipilimumab as immunotherapy of advanced melanoma: a
      critical review.
AB  - Aim: A pooled analysis of the efficacy and toxicity of combination immunotherapy
      versus single-agent ipilimumab in the management of advanced melanoma has been
      conducted. Methodology: Eligible studies included randomized controlled studies
      evaluating ipilimumab-based doublet immunotherapy versus ipilimumab monotherapy
      for the management of unresectable melanoma. Results: Nivolumab/ipilimumab
      combination strategy is associated with a significant improvement in objective
      response rate (odds ratio: 7.38; 95% CI: 3.71-14.67; p < 0.00001) and progression
      free survival (0.42; 95% CI: 0.34-0.52; p < 0.00001) as well as a higher relative
      risk for high-grade elevated alanine aminotransferase (5.58; 95% CI: 2.28-13.67;
      p = 0.0002). Conclusion: This analysis demonstrated that nivolumab/ipilimumab
      combination is associated with a higher objective response rate and progression
      free survival in the management of advanced melanoma.

PMID- 30190894
TI  - The use of dendritic cell vaccinations in melanoma: where are we now?

PMID- 30190895
TI  - Vaccine therapy + dasatinib for the treatment of patients with stage IIIB-IV
      melanoma.

PMID- 30190896
TI  - Current clinical trials for melanoma vaccines: where do we stand?

PMID- 30190897
TI  - Advances in the development of intralesional therapies for melanoma.
AB  - Advances in immune therapy have changed the landscape of advanced melanoma
      treatment. Intralesional therapy is an important type of immune therapy due to
      its efficacy and safety, especially in the setting of locoregional metastases.
      These therapies induce frequent responses in injected lesions as well as distant
      nontreated lesions through a 'bystander' effect of priming an antitumor immune
      response. The culmination of nearly a century of innovation has led to the
      approval of the first US FDA approved intralesional therapy for melanoma in
      talimogene laherparepvec. Numerous efforts to combine intralesional therapies
      with systemic immune checkpoint inhibitors are ongoing, whereby a synergistic
      effect may continue to improve outcomes for patients.

PMID- 30190898
TI  - Talimogene laherparepvec: overview, combination therapy and current practices.
AB  - Talimogene laherparepvec (T-VEC, Imlygic(r), Amgen, CA, USA) is an oncolytic
      herpes simplex type 1 virus used as intralesional therapy for unresectable
      metastatic melanoma in a cutaneous, subcutaneous or nodal location. Talimogene
      laherparepvec selectively replicates within and lyses tumor cells while producing
      granulocyte macrophage colony-stimulating factor, which may promote an immune
      mediated antitumor response. The US FDA approved T-VEC in late 2015 following
      Phase I-III trials that demonstrated safety and efficacy. Future directions for T
      VEC include combination therapies with other systemic immunotherapies such as
      anti-CTLA-4 antibody and anti-PD-1 drugs. Current National Comprehensive Cancer
      Network (NCCN) practice guidelines have added T-VEC as a primary treatment for
      stage IIIB/C and stage IVM1a melanoma patients.

PMID- 30190900
TI  - Welcome to the fourth volume of Melanoma Management and a look back at 2016.

PMID- 30190901
TI  - Are we entering the era of combination therapy for melanoma?

PMID- 30190902
TI  - An interview with Giuseppe Argenziano: an insight into the field of dermoscopy.
AB  - Giuseppe Argenziano speaks to Sebastian Dennis-Beron, Commissioning Editor:
      Giuseppe Argenziano is Full Professor and Head of the Dermatology Unit at the
      University of Campania, Naples, Italy. His main research field is dermato
      oncology. He is an author of numerous scientific articles and books concerning
      dermoscopy, a new technique improving the clinicians detection of benign and
      malignant skin tumors. As a coordinator of a Skin Cancer Unit, he has established
      a successful tertiary, multidisciplinary, referral center particularly devoted to
      the diagnosis and management of patients with skin tumors. Over the past 20 years
      he has supervised over 100 foreign students and 40 residents in dermatology,
      established scientific collaborations with more than 200 colleagues from more
      than 30 nations, and organized more than 50 national and international scientific
      activities, courses and conferences (such as the Consensus Net Meeting on
      Dermoscopy and the First Congress of the International Dermoscopy Society). He is
      co-founder and past president of the International Dermoscopy Society; project
      leader for the development of a high diagnostic technology oncologic center at
      the Arcispedale Santa Maria Nuova IRCCS in Reggio Emilia; faculty member of the
      Master of Science in Dermoscopy and Preventive Dermato-oncology and has
      undertaken a short course in dermoscopy, two e-learning courses by the Medical
      University of Graz and by Cardiff University, respectively; and member of the
      Editorial Board of the Journal of the American Academy of Dermatology. Professor
      Argenziano has authored more than 400 full scientific articles and produced
      landmark primary publications and books in the field of dermoscopy. Over the past
      20 years, he has been invited as speaker and/or chairman in more than 500
      national and international conferences in the field of dermatology. His combined
      publications have received a sum total of more than 8000 citations with an h
      index value of 46.

PMID- 30190899
TI  - Dendritic cell vaccines for melanoma: past, present and future.
AB  - Administering dendritic cells (DC) loaded with tumor-associated antigens (TAA) ex
      vivo is a promising strategy for therapeutic vaccines in advanced melanoma. To
      date the induction of immune responses to specific TAA has been more impressive
      than clinical benefit because of TAA limitations, suboptimal DC and possibly
      immune-checkpoint inhibition. Various products, antigen-loading techniques,
      treatment schedules, routes of administration and adjunctive agents continue to
      be explored. Biologic heterogeneity suggests autologous tumor as the optimal TAA
      source to induce immune responses to the entire repertoire of unique patient
      specific neoantigens. Many questions remain regarding the optimal preparation of
      DC and strategies for antigen loading. Effective DC vaccines should result in
      additive or synergistic effects when combined with checkpoint inhibitors.

PMID- 30190903
TI  - Immunotherapy in malignant melanoma: recent approaches and new perspectives.
AB  - Immunotherapy has radically transformed the management of metastatic malignant
      melanoma. Ipilimumab, a CTLA-4-targeted monoclonal antibody, was the first
      immunotherapeutic drug to reach a survival benefit compared with traditional
      chemotherapy. PD-1 targeted therapies, pembrolizumab and nivolumab, have
      demonstrated, in recent clinical trials, to be even more effective and safer. PD
      1 and CTLA-4 blockade combination appears to improve the outcomes achieved so
      far, although increasing toxicity. However, many questions concerning the optimal
      timing of administration or the most adequate sequence of treatment are yet to be
      answered.

PMID- 30190904
TI  - Lymph node dissection for melanoma: where do we stand?
AB  - The extent and timing of regional lymphadenectomy and its role in patients with
      clinically localized primary melanoma has been the subject of considerable
      debate. While therapeutic lymphadenectomy for clinically positive nodes is
      uniformly accepted, the benefit of regional lymphadenectomy in patients with
      clinically uninvolved lymph nodes potentially harboring micrometastatic disease
      is less clear. Efforts to better select patients for complete regional
      lymphadenectomy after sentinel lymph node biopsy are underway. The future holds
      the promise of more stringent selection criteria and perhaps the identification
      of subgroups of patients for which a therapeutic benefit may be realized.
      Moreover, novel sensitive radiological techniques for detecting in vivo
      micrometastatic nodal disease may improve surgical precision, further decreasing
      potential morbidities of lymphadenectomy.

PMID- 30190906
TI  - When to consider alternatives to front-line immune therapies in metastatic
      melanoma.

PMID- 30190905
TI  - Surgical resection of metastatic melanoma in the era of immunotherapy and
      targeted therapy.
AB  - Melanoma is the deadliest form of skin cancer and one of the few malignancies
      whose incidence is on the rise. The treatment of metastatic melanoma continues to
      be quite challenging, although in recent years, there has been significant
      progress. Current National Comprehensive Cancer Network guidelines list
      immunotherapy, chemotherapy, surgery and clinical trials as potential options for
      patients with metastatic disease but do not clearly recommend which is superior.
      Additionally, when utilizing combined modality treatment there are no clear
      guidelines for the optimal timing of surgery in the treatment of metastatic
      melanoma. In this paper we sought to compile the current evidence and on-going
      trials in order to provide a comprehensive review of the different options
      available and underway in regards to the treatment of metastatic melanoma. It is
      clear that with the responses now seen with systemic immunotherapies and targeted
      therapies, an expanded role for surgery is the logical next step.

PMID- 30190907
TI  - Melanoma treatment guided by a panel of microRNA biomarkers.

PMID- 30190908
TI  - Are PD-1 antibodies safe for use in metastatic uveal melanoma?

PMID- 30190910
TI  - Patient perspective: life in the melanoma patient community and the emergence of
      the melanoma patient conference.
AB  - Imogen Cheese speaks to Sebastian Dennis-Beron, Commissioning Editor: Imogen was
      diagnosed with melanoma in June 2013 (currently stage 2C no evidence of disease
      monitored under Professor Mark Middleton at Oxford) and has since created and
      writes a website blog (www.melanomarollercoaster.co.uk) as well as founded the
      melanoma patient conference in 2015. As an impartial event, the patient
      conference brings together all stakeholders involved in melanoma diagnosis,
      treatment and care; this includes clinicians, charities and crucially, people
      living and dying with melanoma. This means the only end goal for the conference
      are the ongoing needs of patients and families. Imogen's blog has a readership of
      over 2000 people - many of whom are melanoma patients in the UK. She is prolific
      in her contact with these patients on social media and as a result of her blog,
      she has been asked to represent melanoma patients in the UK as their advocacy
      representative at numerous conferences and events across Europe (including
      ECC2015 and the MPNE annual events in Brussels). Patients reach out to Imogen on
      a daily basis asking for support and seeking a means to improve their knowledge
      and obtain access to better care and information on the latest drugs and trials
      in the UK. She is a member of the Melanoma Patient Network Europe and speaks
      daily to over 300 patients on an online support group on social media. Imogen was
      invited by the British Skin Foundation to support them in establishing a skin
      cancer specific arm of their charity called ITTakes7 and has worked directly with
      Melanoma UK on various projects for patient interaction and information
      gathering. She is connected with Cancer Research UK as a patient representative
      with the ECMC network and involved with the Oxford hospitals as an advisor for
      their public engagement and planning. Imogen can be found on twitter at
      @MelanomaBlog.

PMID- 30190909
TI  - What is new in melanoma after European Cancer Congress 2017?

PMID- 30190911
TI  - Making melanoma therapy personal: an interview with Dr Keiran Smalley for
      Melanoma Management.
AB  - Dr Smalley earned his PhD in Pharmacology from the University of Cambridge, UK,
      in 2001. He worked as a post-doctoral fellow in the Oncology Department of
      University College London, the Institute of Cancer Research, Fulham Road and the
      Wistar Institute, PA, USA. Currently, Dr Smalley is a Professor in the
      Departments of Tumor Biology and Cutaneous Oncology at the Moffitt Cancer Center,
      FL, USA. He is also currently the Donald A Adam Endowed Chair in Melanoma
      Research and is the Director of the Melanoma and Skin Cancers Center of
      Excellence. The lab of Dr Smalley focuses upon the development of targeted
      therapy strategies for melanoma and is currently funded by the NCI, the
      pharmaceutical industry and a number of philanthropic sources. Dr Smalley's work
      is highly translational in nature and work from his lab has led to the initiation
      of a number of clinical trials. To date, Dr Smalley has published over 120 papers
      in top peer-reviewed journals including Cancer Research, Cancer Discovery, Cancer
      Cell, New England Journal of Medicine, the Proceedings of the National Academy of
      Sciences, the Lancet, Gastroenterology and Clinical Cancer Research. He currently
      sits on the editorial boards of Clinical Cancer Research, Biochemical
      Pharmacology, Drugs, Melanoma Research and the American Journal of Clinical
      Dermatology and is the Associate Editor of Pharmacological Research. Dr Smalley
      is a charter member of the Basic Mechanisms of Cancer Therapeutics Study Section
      for the NCI/NIH and has served on many other peer review panels for the
      Department of Defense, the state of Texas and numerous melanoma research
      foundations. He has also fulfilled advisory roles with the University of
      Pennsylvania, the University of Pittsburgh and a number of pharmaceutical
      companies. Dr Smalley has been a visiting professor at the University of Sao
      Paulo, Brazil in 2011 and in 2014 received a Science Without Borders Scholarship
      from the Brazilian Government.

PMID- 30190912
TI  - Malignant melanoma of the small bowel presenting with intussusception in a woman:
      a case report.
AB  - Primary malignant melanoma originating in the small bowel is very rare. We report
      the case of primary malignant melanoma of the small bowel with secondary
      intussusception in a 51-year-old female with no prior history of cutaneous
      melanoma. The patient was admitted to the hospital for clinical bowel obstruction
      after 6 months of varying symptoms of antecedent syncopal events secondary to
      profound anemia due to iron deficiency followed later by vomiting, abdominal pain
      and weight loss. A CT scan showed intussusception and she underwent a small bowel
      resection. Diagnosis of malignant melanoma was confirmed post-operatively
      following immunohistochemistry. The patient history and postoperative
      investigation excluded the existence of a primary lesion elsewhere. Our case
      represents an aggressive primary small bowel melanoma presenting as
      intussusception.

PMID- 30190913
TI  - A surgical perspective report on melanoma management.
AB  - Management of melanoma includes wide excision with adequate margins and lymph
      node biopsy depending on the depth of the lesion, with subsequent completion
      lymphadenectomy for positive sentinel node. Locally advanced disease can be
      approached in several different ways depending on a variety of patient and
      disease-specific factors. These include surgical resection, isolated limb
      perfusion and infusion and intralesional injection therapy such as talimogene
      laherparepvec, IL-2 and Bacille Calmette-Guerin. Ongoing controversy exists
      regarding the utility of completion lymphadenectomy, and trials such as MSLT-2
      will attempt to shed light on this issue. The future of melanoma management will
      likely focus on expanding the use of immunotherapy, allowing for narrower
      surgical margins, particularly in sensitive anatomic areas, and limiting the
      number of completion lymphadenectomies.

PMID- 30190914
TI  - Improving the diagnosis and treatment of acral melanocytic lesions.
AB  - Melanocytic lesions of acral sites are common, with an estimated prevalence of 28
      36% in the USA. While the majority of these lesions are benign, differentiation
      from acral melanoma (AM) is often challenging. AM is a unique subtype of
      melanoma, with distinct molecular characteristics that are thought to contribute
      to its high rate of locoregional recurrence and worse prognosis. The advent of
      dermoscopy has since improved the diagnostic accuracy of AM, resulting in earlier
      detection and arguably improved survival. Additionally, the identification of
      unique genomic amplifications in AM invites the potential for future AM-specific
      targeted therapies. Herein, we discuss the importance of dermoscopy in the
      diagnosis of acral melanocytic lesions and review the treatment strategies for
      AM.

PMID- 30190916
TI  - Can we improve melanoma detection methods?

PMID- 30190917
TI  - Utility of ipilimumab in melanoma patients who progress on anti-PD-1 therapy.

PMID- 30190915
TI  - The role for chemotherapy in the modern management of melanoma.
AB  - The treatment of malignant melanoma has changed beyond recognition in the last 7
      years. Where previously single agent dacarbazine was often the only treatment
      used for advanced disease, now there are potentially multiple lines of treatment,
      based on immunotherapy and targeted treatment options, either as monotherapy or
      in combination. In this brave new world the question arises, does chemotherapy
      still have any relevance in the modern management of melanoma? In this review, we
      summarize the various chemotherapeutic options that have been trialled in
      melanoma to date, and discuss the role chemotherapy may still play in treating
      melanoma, potentially in combination with more novel agents, or in certain
      subtypes of melanoma.

PMID- 30190918
TI  - Advantages of whole-genome sequencing for identification of tumor etiology and
      clinically actionable genomic aberrations: lessons from the Australian Melanoma
      Genome Project.

PMID- 30190919
TI  - Anti-PD-1 monotherapy versus anti-PD1 plus anti-CTLA4 in advanced melanoma: how
      do we decide?

PMID- 30190920
TI  - Survivor and patient advocate: an interview with T.J. Sharpe.
AB  - T.J. Sharpe speaks to Sebastian Dennis-Beron, Commissioning Editor: T.J. Sharpe
      is a stage IV melanoma patient who shares his journey through cancer in the
      Patient #1 Blog [1]. He was diagnosed in August 2012 with melanoma tumors in
      multiple organs; since then, he has undergone six surgeries and four
      immunotherapy treatments over two different clinical trials. The initial failures
      and subsequent significantly positive response have been chronicled in his blog
      posts since January 2013. His story is about life with a serious illness, and the
      mental and emotional hurdles a patient must clear. He writes how a cancer
      patient's challenges mirror those many face, and portrays life through the
      optimistic prism of a patient who is on the long, winding road toward overcoming
      melanoma's long odds and deadly consequences. He also shares the latest melanoma
      and oncology research breakthroughs and advocacy events, and initiatives to help
      others avoid, detect or educate themselves on cancer. As part of his advocacy, he
      attends cancer and melanoma conferences, reporting on the latest medical
      breakthroughs through his blog to other cancer patients. He also partners with
      advocacy organizations, clinical trial groups and the pharmaceutical industry to
      bring awareness to cancer research and developments. His efforts have been
      recognized by several organizations, including the Melanoma Research Foundation,
      Melanoma International Foundation, Patient Power, Forbes, Merck, GlaxoSmithKline,
      the Drug Information Association and the Milken Institute's FasterCures. In
      December 2014, he was able to share his story on Capitol Hill in a special
      session promoting immunotherapy research to lawmakers. A South Jersey native,
      T.J. lives in Fort Lauderdale with his wife Jennifer and two young children,
      Josie and Tommy. He is active in health and wellness initiatives, including
      melanoma/cancer awareness runs and bike rides, and an avid yoga participant. He
      also serves on the Board of Directors of A Prom to Remember, a 501

PMID- 30190921
TI  - Immune checkpoint inhibitors in the treatment of advanced mucosal melanoma.
AB  - Immunotherapy with immune checkpoint inhibitors is the standard of care in the
      treatment of advanced melanoma. Treatment outcome of these agents is less defined
      for the rare subtype of mucosal melanoma. In this single-institutional case
      series, the objective response rate was low at 11.8%, but durable response was
      seen, including a complete response to first-line ipilimumab and to second-line
      pembrolizumab. Survival remained poor; at the median follow-up of 10.1 months,
      the median progression-free survival and overall survival were 3.1 and 8.8 months
      respectively. Nevertheless, among the few responders, survival of up to 56+
      months was observed. Other treatment strategies need to be explored to improve
      treatment outcome for this rare subtype.

PMID- 30190922
TI  - Prognostic molecular testing in melanoma: ready for prime time?

PMID- 30190923
TI  - Anti-PD-1 and PD-L1 antibodies in metastatic melanoma.

PMID- 30190924
TI  - Has the melanoma information tsunami become a maelstrom?

PMID- 30190925
TI  - Management of the cutaneous adverse effects of antimelanoma therapy.
AB  - The advent of targeted therapy and immunotherapy has revolutionized the
      management of advanced melanoma. However, these novel therapies are associated
      with adverse effects (AEs), of which cutaneous toxicities are the most frequently
      observed. These cutaneous AEs can exert significant morbidity and impact on
      patient quality of life, hence the recognition and management of AEs is
      fundamental in preventing interruption or cessation of survival-prolonging
      treatments. Additionally, knowledge of these AEs are necessary in order for
      healthcare professionals to counsel patients when starting treatment and in the
      initiation of AE prophylaxis. The incidence and clinical presentation of the
      cutaneous toxicities of novel melanoma therapies will be discussed, and treatment
      guidelines provided.

PMID- 30190926
TI  - An update on the relevance of vaccine research for the treatment of metastatic
      melanoma.
AB  - Signal transduction inhibitors and anticheckpoint antibodies have significantly
      improved survival for metastatic melanoma patients, but most still die within 5
      years. Vaccine approaches to induce immunity to well-characterized melanoma
      associated antigens, or to antigens expressed on allogeneic tumor cell lines,
      have not resulted in approved agents. Despite the limitations associated with the
      immunosuppressive tumor microenvironment, there now is one intralesional
      autologous vaccine approved for patients who have primarily soft-tissue
      metastases. There is continued interest in patient-specific vaccines, especially
      dendritic cell vaccines that utilize ex vivo loading of autologous antigen, thus
      bypassing certain in vivo immunosuppressive cells and cytokines. Because of their
      mechanism of action and limited toxicity, they are potentially synergistic or
      additive to other antimelanoma therapies.

PMID- 30190927
TI  - Gastrointestinal adverse events with combination of checkpoint inhibitors in
      advanced melanoma: a systematic review.
AB  - Introduction: Immunotherapies, including checkpoint inhibitors (CIs) such as
      cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed death-1 (PD-1)
      inhibitors, are revolutionizing the treatment of advanced melanoma. Combining
      CTLA-4 and PD-1 inhibitors provides additional clinical benefit compared with
      single agents alone. However, combination therapy can increase the incidence of
      gastrointestinal adverse events (GI AEs). This systematic review assessed the
      epidemiological, clinical, economic, and humanistic burden of GI AEs due to
      combination CIs in advanced melanoma. Methods: MEDLINE, EMBASE, and the Cochrane
      Library were systematically searched (December 2011 to December 2016) to identify
      primary studies, systematic reviews, meta-analyses, and conference proceedings
      (2014-2016) evaluating adults treated with >=2 CIs for advanced melanoma.
      Results: Of the 3391 identified articles, 14 were included. Most studies examined
      the ipilimumab plus nivolumab combination. Any grade and grade 3-4 GI AEs
      occurred in more patients receiving ipilimumab plus nivolumab versus ipilimumab
      or nivolumab alone. The most common grade 3-4 GI AEs were diarrhea and colitis.
      Grade 3-4 colitis occurred in more patients receiving ipilimumab plus nivolumab.
      However, grade 3-4 diarrhea occurred at the same rate as ipilimumab alone. GI AEs
      developed with ipilimumab plus nivolumab approximately 6.6 weeks after initiating
      treatment. No studies assessing the economic or humanistic burden of GI AEs were
      identified. Conclusion: GI AEs occurred at a higher rate and greater severity in
      patients treated with ipilimumab plus nivolumab versus ipilimumab or nivolumab
      monotherapy. The lack of research on economic and humanistic burden of GI AEs
      with combination CIs for advanced melanoma represents an unmet need in the
      literature and should be explored in future studies.

PMID- 30190929
TI  - Continuing and new roles for surgery in the management of patients with stage IV
      melanoma.

PMID- 30190928
TI  - Interferon is associated with improved survival for node-positive cutaneous
      melanoma: a single-institution experience.
AB  - Aim: We assessed the role of adjuvant interferon on relapse-free survival (RFS),
      distant metastasis-free survival (DMFS) and overall survival (OS) in node
      positive melanoma patients. Methods: We retrospectively reviewed 385 node
      positive patients without distant metastatic disease treated from 1998 to 2015.
      The surgery was therapeutic lymph node dissection (LND, n = 86) or sentinel lymph
      node biopsy +/- completion LND (n = 270). 128 patients (33.2%) received adjuvant
      interferon. Results: After a median follow-up of 70 months, interferon was
      associated with improved RFS (hazard ratio [HR]: 0.55; p < 0.001), DMFS (HR:
      0.59; p < 0.001) and OS (HR: 0.61; p = 0.003), controlling for tumor and nodal
      stage, node size, sex, primary site, adjuvant therapy and extracapsular
      extension. In an exploratory age-matched comparison of patients treated with (n =
      67) and without (n = 233) adjuvant immunotherapy, interferon still showed
      improved RFS, DMFS and OS. Conclusion: Adjuvant interferon appears to improve OS
      among node-positive melanoma patients in a modern experience, providing context
      for comparison in the adjuvant therapy landscape.

PMID- 30190931
TI  - Real-world experience with pembrolizumab toxicities in advanced melanoma
      patients: a single-center experience in the UK.
AB  - Aim: We aimed to characterize the safety profile of pembrolizumab in advanced
      melanoma patients at our center to better reflect 'real-world' data on anti-PD-1
      inhibitors. Materials & methods: At our institution, 58 ipilimumab-naive and 30
      ipilimumab-treated patients with advanced melanoma who have received
      pembrolizumab between June 2014 and June 2017 were included for analysis.
      Results: Incidence of any-grade and grade 3/4 toxicities were 81.8% (n = 72) and
      12.5% (n = 11), respectively. The most common side effects were skin-related
      (61.4%, n = 54) and gastrointestinal-related (51.1%, n = 45) events. In total,
      25% of patients required oral steroids to manage immune-related adverse events
      with a median cumulative prednisolone dose of 683 mg (range: 40-3745 mg).
      Conclusion: Pembrolizumab is well tolerated in 'real-world' patients and severe
      toxicities can be effectively managed with systemic steroids.

PMID- 30190930
TI  - Advances in the use of reflectance confocal microscopy in melanoma.
AB  - In vivo reflectance confocal microscopy (RCM) is a noninvasive high-resolution
      skin imaging tool that has become an important adjunct to clinical exam,
      dermoscopy and histopathology assessment, in the diagnosis and management of
      melanoma. RCM generates a horizontal view of the skin, whereby cellular and
      subcellular (e.g., nuclei, melanophages, collagen) structures, to the level of
      the upper dermis, are projected onto a screen at near-histological resolution.
      Morphologic descriptors, standardized terminology, and diagnostic algorithms are
      well established for the RCM assessment of melanoma, melanocytic, and
      nonmelanocytic lesions. Clinical applications of RCM in melanoma are broad and
      include diagnosis, assessment of large lesions on cosmetically sensitive areas,
      directing areas to biopsy, delineating margins prior to surgery, detecting
      response to treatment and assessing recurrence. This review will provide an
      overview of RCM technology, findings by melanoma subtype, clinical applications,
      as well as explore the accuracy of RCM for melanoma diagnosis, pitfalls and
      emerging uses of this technology ex vivo.

PMID- 30190933
TI  - Hepatic Oncology: a journal for all stakeholders in liver cancer management.

PMID- 30190934
TI  - Impact of a shortened surveillance interval on hepatocellular carcinoma survival.

PMID- 30190937
TI  - Journal Watch: Our expert highlights the most important research articles across
      the spectrum of topics relevant to the field of hepatic oncology.

PMID- 30190935
TI  - What do we know about the etiology of hepatoblastoma?

PMID- 30190938
TI  - Interview: Challenges and prospects for liver cancer management: treatment,
      prevention and collaboration.
AB  - Dr Shahid Khan qualified in Medicine at Guys Hospital Medical School (London, UK)
      in 1994. His studies in liver cancer led to a PhD from the University of London
      in 2003 and he was appointed Consultant in Gastroenterology and Hepatology at St
      Mary's and Hammersmith Hospitals, Imperial College London Healthcare NHS Trust;
      and a Clinical Senior Lecturer at Imperial College London in 2007. Dr Khan has
      lectured on liver disease nationally and internationally at hepatology and
      gastroenterology conferences, including state-of-the-art and invited
      presentations. He is the lead author on the UK National Guidelines for biliary
      cancer and was on the International Liver Cancer Association panel for the
      International Guidelines. He has published extensively in the medical literature,
      including original research articles, reviews and book chapters. Dr Khan is a
      Fellow of the Royal College of Physicians of the UK, and a member of the British
      Medical Association, the British Association for the Study of the Liver, the
      British Society of Gastroenterology, the European Association for the Study of
      the Liver, the American Association for the Study of the Liver Diseases and the
      International Liver Cancer Association.

PMID- 30190932
TI  - Melanoma & nuclear medicine: new insights & advances.
AB  - The contribution of nuclear medicine to management of melanoma patients is
      increasing. In intermediate-thickness N0 melanomas, lymphoscintigraphy provides a
      roadmap for sentinel node biopsy. With the introduction of single-photon emission
      computed tomography images with integrated computed tomography (SPECT/CT), 3D
      anatomic environments for accurate surgical planning are now possible. Sentinel
      node identification in intricate anatomical areas (pelvic cavity, head/neck) has
      been improved using hybrid radioactive/fluorescent tracers, preoperative
      lymphoscintigraphy and SPECT/CT together with modern intraoperative portable
      imaging technologies for surgical navigation (free-hand SPECT, portable gamma
      cameras). Furthermore, PET/CT today provides 3D roadmaps to resect 18F
      fluorodeoxyglucose-avid melanoma lesions. Simultaneously, in advanced-stage
      melanoma and recurrences, 18F-fluorodeoxyglucose-PET/CT is useful in clinical
      staging and treatment decision as well as in the evaluation of therapy response.
      In this article, we review new insights and recent nuclear medicine advances in
      the management of melanoma patients.

PMID- 30190939
TI  - Systemic therapy for hepatocellular carcinoma.
AB  - Optimal treatment of hepatocellular carcinoma (HCC) is clinically challenging.
      Systemic treatment for advanced HCC was limited until the approval of sorafenib.
      This discovery resulted in the advent of many clinical trials. An ongoing Phase
      III trial is examining the benefit of adjuvant sorafenib. Utilization of
      doxorubicin-eluting bead embolization may offer safer treatment in eligible HCC
      patients. The use of systemic treatment peritransarterial chemoembolization is
      also being investigated. Many targeted therapies are being explored as first
      /second-line treatment options in advanced HCC. The potential benefit of c-MET
      inhibitors, particularly in those with advanced, MET high expression HCC, may
      result in new systemic patient-directed targeted medicinal approaches. Remaining
      dilemmas query the appropriate management of patients with advanced Child-Pugh B,
      HCC and those recurring post-transplant.

PMID- 30190940
TI  - Assessing resectability in cholangiocarcinoma.
AB  - Assessment of surgical resectability in cholangiocarcinoma is more complicated
      than other gastrointestinal malignancies and remains unestablished. According to
      the primary origin and tumor extent, the applied surgical procedure varies from
      extrahepatic bile duct resection to right or left trisectionectomy concomitant
      with pancreatoduodenectomy. Portal vein resection and reconstruction during
      hepatectomy has been feasible. Thanks to the availability of new microscopic
      surgical techniques, hepatic arterial resection and reconstruction have also come
      to be applied for locally advanced cholangiocarcinoma cases. These vascular
      surgical techniques can expand surgical indications for advanced
      cholangiocarcinoma. On the other hand, determination of the tumor extent or
      staging still remains difficult and imprecise. The endoscopic approach has come
      to play significant roles both for preoperative biliary drainage and tumor
      staging. Estimation of the functional reserve of future remnant liver in
      cholestatic patients still remains unresolved. Hepatobiliary surgeons should
      carefully estimate the safety of the surgical procedure in each individual
      patient requiring extensive hepatobiliary resection. Early establishment of the
      measurement methods of the functional capacity of future remnant liver is an
      important and urgent issue for assessing safer surgical resectablity of
      cholangiocarcinoma.

PMID- 30190941
TI  - Evolving role of vascular resection and reconstruction in hepatic surgery for
      malignancy.
AB  - Primary and secondary hepatic malignancies, including hepatocellular cancer,
      cholangiocarcinoma and metastatic disease from colorectal cancer continue to
      increase in incidence worldwide, and remain diseases with a high mortality. Liver
      resection, with negative margins, is associated with improved survival and better
      quality of life over nonoperative treatment. As liver resection continues to
      evolve, aggressive centers are increasingly using vascular resection and
      reconstruction to achieve negative margins and improve outcomes. As these
      resections become more common, the morbidity and mortality associated with these
      complex surgical procedures is decreasing. Currently, resections of the portal
      vein are becoming routine in major liver and pancreatic resections, and
      experience with hepatic artery, hepatic vein and inferior vena cava resections is
      increasing. This review paper looks at the current indications, techniques and
      outcomes for major vascular resection in hepatic malignancy.

PMID- 30190942
TI  - Ablation therapy for hepatocellular carcinoma: past, present and future
      perspectives.
AB  - Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death
      worldwide, and is most commonly found in the setting of liver cirrhosis.
      Treatment of HCC must consider both the tumors present, as well as the remaining
      dysfunctional liver that both hinders treatment and can produce additional HCC
      over time. Ablation is an evolving part of the multimodality treatment approach
      to HCC that can effectively destroy tumors while preserving surrounding liver
      parenchyma. New technologies have made ablation an indispensable tool in the
      treatment of all stages of HCC. This review presents the history, present
      technologies and future potential of ablation in the treatment of HCC.

PMID- 30190943
TI  - Rationale for ablation of oligometastatic disease and the role of stereotactic
      body radiation therapy for hepatic metastases.
AB  - Management paradigms for metastatic solid tumors are evolving. Once regarded as
      uniformly incurable, today there is recognition of an intermediate
      oligometastatic state, where ablation of metastatic foci may improve disease
      control and prolong survival. In the setting of limited colorectal liver
      metastases, hepatic resection has resulted in favorable long-term outcomes, but
      is technically unsuitable for most patients. Stereotactic body radiation therapy
      represents an effective, noninvasive means of tumor ablation, supported by a
      large body of prospective evidence specific to hepatic metastases. This review
      examines the current rationale for ablation of oligometastatic disease, including
      various objectives beyond indefinite disease-free survival. The role of
      stereotactic body radiation therapy for ablation of hepatic metastases is then
      comprehensively reviewed.

PMID- 30190944
TI  - Insight into hepatocellular carcinoma biology with gadoxetate disodium-enhanced
      MRI.
AB  - The current algorithm for the imaging diagnosis of hepatocellular carcinoma
      accurately detects large, progressed tumors displaying the classical imaging
      features of arterial hyperenhancement with 'washout' and/or 'capsule' appearance.
      Liver MRI with the relatively newer hepatobiliary agent, gadoxetate disodium,
      provides information on hepatocellular function in addition to vascularity,
      facilitates detection of small progressed tumors, as well as early/vaguely
      nodular tumors, and shows promise for characterizing hepatocellular carcinoma
      biology. Prediction of tumor grade, presence of biliary and stem cell markers,
      microvascular invasion, future hypervascularization and post-treatment recurrence
      have all been studied with gadoxetate disodium-enhanced MRI with encouraging
      results. Incorporation of gadoxetate disodium-enhanced MRI into standard
      diagnostic and management algorithms will likely unfold in the future.

PMID- 30190948
TI  - Limitations of screening for hepatocellular carcinoma.

PMID- 30190946
TI  - Surgical management of colorectal liver metastases: a European perspective.
AB  - The treatment of colorectal cancer metastatic to the liver is increasingly
      complex as a result of changes in the patient population, advances in
      preoperative staging, changing definitions of resectability, advances in surgical
      technique and the expanding chemotherapeutic armamentarium. Management of these
      patients within a multidisciplinary team is increasingly important and associated
      with better outcomes. In patients with irresectable hepatic metastases, high
      secondary resection rates can be achieved with multiagent chemotherapy when
      managed in conjunction with a liver specialist. Perioperative mortality rates are
      reducing but morbidity remains high, and enhanced recovery could help reduce
      morbidity. Despite the advancing age and comorbidity of the patient population,
      multimodal management is likely to lead to further improvements in perioperative
      and long-term outcomes.

PMID- 30190945
TI  - STAT3 in hepatocellular carcinoma: new perspectives.
AB  - Chronic liver damage and inflammation are strong promoters of hepatocellular
      carcinoma (HCC) formation. HCC cells communicate with inflammatory and stromal
      cells via cytokine/chemokine signals. These heterotypic interactions inhibit
      immunologic anticancer activities and promote protumorigenic activities, such as
      angiogenesis or invasiveness. STAT3 mediates several reciprocal interactions
      between liver cancer cells and stromal cells and modulates preconditions of tumor
      formation such as chronic inflammation. Therefore, activation of STAT3 is
      considered as a tumor-promoting event in HCC formation. However, the oncogenic
      role of STAT3 in cancers has been challenged by several reports that suggest a
      tumor-suppressive activity. Here we discuss tumor-promoting and tumor-suppressive
      effects of cytokine-activated STAT3 in HCC.

PMID- 30190951
TI  - Journal Watch: Our expert highlights the most important research articles across
      the spectrum of topics relevant to the field of hepatic oncology.

PMID- 30190949
TI  - Who should undergo liver transplantation for hepatocellular carcinoma? Ablate,
      wait ... and see!

PMID- 30190947
TI  - Current state of nonsurgical therapies for cholangiocarcinoma.
AB  - Cholangiocarcinomas (CCCs) are rare tumors that are derived from the epithelial
      cell lining of the bile ducts. They can be classified as intrahepatic,
      extrahepatic-perihilar and extrahepatic-distal tumors. The prognosis of CCCs is
      poor as, in many cases, they are diagnosed at advanced stages, at which point
      curative surgical resection is not possible. Furthermore, most patients will
      experience a tumor recurrence despite initial complete CCC resection. Therefore,
      alternative/additional therapeutic strategies are needed to improve tumor- and
      recurrence-free survival after surgery as well as tumor control in patients with
      advanced disease. In clinical practice, apart from systemic chemotherapies for
      the therapeutic management of CCCs, locoregional as well as multimodal strategies
      are available, including external and internal radiation therapies. This review
      focuses on the currently available nonsurgical therapies for patients with CCCs,
      alone or in combination with other modalities, and on evolving therapeutic
      concepts that are being explored in clinical studies.

PMID- 30190952
TI  - Ask the Experts: Management of hepatic metastases from neuroendocrine cancer.
AB  - David M Nagorney, Professor of Surgery, was born and raised in Kansas City (KS,
      USA) in the USA. He graduated from the University of Kansas (KS, USA), the
      University of Kansas Medical School and the Mayo Graduate School of Medicine (MN,
      USA). He completed his general surgery residency at the Mayo Graduate School of
      Medicine and served as a research fellow there. He was selected as a Mayo
      Foundation Scholar and completed his training at the Royal Postgraduate Medical
      School, Hammersmith Hospital (London, UK). He is an accomplished general surgeon,
      holding a status of Professor of Surgery, specializing in the treatment of
      gastroenterologic and liver oncologic diseases at the Mayo Clinic Department of
      Surgery (MN, USA). Presently, he is the program director for the Mayo Clinic
      Department of Surgery Fellowship Scholars. Nagorney is a member of numerous
      national and international surgical societies focusing on hepato-pancreatic
      biliary surgery and surgical oncology.

PMID- 30190953
TI  - Tivantinib in MET-high hepatocellular carcinoma patients and the ongoing Phase
      III clinical trial.
AB  - There is no available effective systemic treatment for patients with advanced
      hepatocellular carcinoma (HCC) who are intolerant of sorafenib or who have
      disease that has progressed on sorafenib. In Phase I and II studies, tivantinib
      (ARQ 197), an oral inhibitor of MET, demonstrated promising antitumor activity in
      patients with HCC, both as monotherapy and in combination with sorafenib. A
      randomized Phase II trial in second-line HCC showed improved overall survival
      (hazard ratio: 0.38; p = 0.01) in patients with MET-high tumors, as demonstrated
      by immunohistochemistry, treated with tivantinib versus placebo. Here we present
      the treatment rationale and study design of the METIV-HCC Phase III study. This
      randomized, double-blind study will investigate tivantinib monotherapy as second
      line treatment in patients with advanced, pretreated, MET-high HCC. Approximately
      303 patients will be randomized 2:1 to tivantinib or placebo for the purpose of
      analyzing the primary end point. Tivantinib will be dosed at 120 mg twice daily,
      and treatment will continue until disease progression, unacceptable toxicity,
      patient or physician decision to discontinue, or death. The primary end point of
      this study is overall survival, while secondary end points include progression
      free survival and safety. All patients will be tested for biomarkers. If the
      primary objective is achieved, this study will provide the first effective
      therapy for a biologically selected patient population in HCC.

PMID- 30190954
TI  - Sorafenib for the treatment of hepatocellular carcinoma.
AB  - The multikinase inhibitor sorafenib, which inhibits targets related to tumor cell
      proliferation and angiogenesis, was the first systemic agent to demonstrate a
      significant improvement in the overall survival for patients with advanced
      hepatocellular carcinoma (HCC) in two large randomized controlled Phase III
      trials. Together with its manageable safety profile (mainly diarrhea, hand-foot
      skin reaction and fatigue), sorafenib was approved for the treatment of patients
      with (unresectable) HCC in 2007. Since then, sorafenib has been established as
      the standard of care in Child-Pugh A patients with advanced HCC or in those
      ineligible for or after failure of locoregional therapies in the intermediate
      stage of the disease. This article summarizes current knowledge and future
      perspectives regarding the use of sorafenib in patients with HCC.

PMID- 30190955
TI  - Chemoembolization with DC BeadTM for the treatment of hepatocellular carcinoma:
      an update.
AB  - In this review, DC BeadTM for the treatment of hepatocellular carcinoma is
      discussed. The embolic device and its mechanism of action is described, focusing
      on the clinical application and the preclinical background. Guidelines for
      patient selection and management, along with technical considerations for the
      appropriate use are provided. Clinical details including local response,
      comparison with conventional chemoembolization and bland embolization, survival
      and safety issues are also discussed in detail.

PMID- 30190956
TI  - Current role of transarterial chemoembolization and radioembolization in the
      treatment of metastatic colorectal cancer.
AB  - In this article, we review two liver-directed therapies that are currently used
      for the palliative treatment of primary and secondary hepatic malignancies,
      transcatheter arterial chemoembolization (TACE), including a new type of TACE
      with drug-eluting beads, and radioembolization. Important developments and
      administration techniques for all therapies are discussed, as well as their
      integration into the current routine clinical care for management of metastatic
      colorectal cancer. According to published data from clinical trials, as presented
      in this review, both radioembolization and TACE/TACE with drug-eluting beads have
      been proven to be safe and effective in selected patients with chemorefractory
      liver metastases from colorectal cancer. For patients with unresectable liver
      only or liver-dominant disease who have failed standard chemotherapy options or
      for whom chemotherapy is contraindicated, new modalities, such as those
      discussed, are particularly valid and promising if clinical guidelines for
      patient selection and treatment administration are followed.

PMID- 30190957
TI  - Endoscopic treatment options for cholangiocarcinoma.
AB  - Cholangiocarcinomas are often locally advanced or have metastasized, and at the
      time of diagnosis individuals often have a poor prognosis. Endoscopic treatment
      options traditionally include biliary decompression via stenting to allow for
      systemic chemotherapy and radiotherapy, with self-expanding metal biliary stents
      being preferred. Recent developments in locoregional therapy delivered
      endoscopically, such as photodynamic therapy and radiofrequency abalation, have
      shown promising results in improving patient survival.

PMID- 30190959
TI  - Preventing hepatocellular carcinoma: the crucial role of chronic hepatitis B
      monitoring and antiviral treatment.

PMID- 30190961
TI  - Management of hepatocellular carcinoma: time to be resilient.

PMID- 30190958
TI  - Alterations in the expression and activity of pre-mRNA splicing factors in
      hepatocarcinogenesis.
AB  - Hepatocellular carcinoma (HCC) is a molecularly complex tumor that is resistant
      to standard and targeted therapies, and thus a deadly disease. In this context,
      the identification of key alterations driving HCC development is therefore
      essential. The implementation of next-generation sequencing techniques has
      underscored earlier realizations of the marked dysregulation of pre-mRNA splicing
      in HCC. Impairments in alternative splicing may lead to the expression of
      protumorigenic protein isoforms and to the generation of unstable mRNA species.
      Mechanistically, mutations in key nucleotides are responsible for many of these
      alterations in different types of tumors. However, changes in the expression of
      factors involved in the regulation of the splicing machinery are also important
      determinants in the derangement of pre-mRNA splicing. Here we discuss recent
      reports on the alteration of splicing factors in HCC, the pathological
      significance of these changes, and the identification of cell signaling pathways
      leading to the missplicing of genes in hepatocarcinogenesis.

PMID- 30190962
TI  - SIR-Spheres yttrium-90 radioembolization for the treatment of unresectable liver
      cancers.
AB  - Transarterial radioembolization with yttrium-90 resin microspheres (SIR-Spheres;
      Sirtex Medical Limited, Sydney, Australia) is a liver-directed therapy that is
      gaining recognition as a treatment option for liver-dominant primary and
      metastatic cancers. The incidence of complications is low and can be further
      reduced by patient selection and rigorous pretreatment assessment. Ideal
      candidates for radioembolization have preserved liver function without ascites or
      encephalopathy, Child-Pugh score <7 and limited lung shunting. Phase III
      randomized controlled trials (RCTs) against other liver-directed therapies are
      lacking for intermediate-stage hepatocellular carcinoma. However, preliminary
      data from a recent RCT has suggested that radioembolization has a similar time-to
      progression and comparable toxicity to selective chemoembolization. Phase II/III
      RCTs are now ongoing to evaluate the combination of radioembolization with
      systemic therapies in advanced-stage hepatocellular carcinoma and metastatic
      liver-dominant colorectal cancer in order to expand the treatment opportunities
      for patients with cancers in the liver.

PMID- 30190963
TI  - Rationale of transcatheter intra-arterial therapies of hepatic cancers.
AB  - Transcatheter, intra-arterial therapies for primary and metastatic hepatic
      malignancies comprise angiographically guided procedures that provide for the
      administration of tumoricidal agents directly to liver tumors. These locoregional
      therapies have demonstrated encouraging clinical outcomes for liver tumors that
      are otherwise not amenable or not responsive to standard surgical or systemic
      treatments. This article provides a review of transcatheter therapies for hepatic
      cancers and reported clinical outcomes.

PMID- 30190965
TI  - Liver transplantation for hepatocellular carcinoma: how far have we come and what
      is the future?
AB  - Liver transplantation is the best treatment for hepatocellular carcinoma in the
      setting of chronic liver disease, completely removing malignancy and underlying
      diseased liver tissue. Technical aspects of liver transplantation have improved
      over the years, along with outcomes. But challenges continue in the areas of
      expanding existing indications for transplant with limited organ supply, calling
      for optimization of patient selection and the development of alternative or
      adjunctive treatment options. Expansion of existing transplant criteria will help
      identify patients most likely to have good outcomes. Locoregional and systemic
      treatments showing therapeutic promise are being investigated for use in
      achieving acceptable oncologic effect. Improvements in post-transplant treatment
      and continued attempts to enlarge the donor pool will continue to provide avenues
      for further improvements in outcomes.

PMID- 30190966
TI  - miRNAs: new tools for molecular classification, diagnosis and prognosis of
      hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) remains one of the most common malignancies
      worldwide, ranking as the third leading cause of cancer-related death. With
      recent advances in understanding HCC biology, progress has been made in early
      detection and management of HCC; however, its prognosis remains dismal. Novel
      biomarkers for HCC that are acceptable for clinical utility are urgently in need.
      Recently, miRNA has emerged as an important class of gene regulator that controls
      various cellular processes including cancer development. In HCC, miRNAs are
      frequently dysregulated, and studies have shown great promises of miRNAs as
      biomarkers for tumor classification, diagnosis and prognosis. Given miRNAs are
      highly stable in blood plasma and serum, they are suggested as a new class of
      noninvasive biomarker for detection of HCC. In this article, we provide an up-to
      date review of the recent findings of the use of miRNAs in molecular
      classification of HCC tumors, diagnosis and prognosis.

PMID- 30190968
TI  - The biological and clinical challenge of liver cancer heterogeneity.

PMID- 30190964
TI  - Mechanisms of hepatocarcinogenesis in chronic hepatitis C.
AB  - Infection with hepatitis C virus (HCV) is a major risk factor for hepatocellular
      carcinoma. The genetic changes that drive cancer development are heterogeneous
      and how chronic hepatitis C promotes the initiation of hepatocellular carcinoma
      is incompletely understood. Cancer typically arises in the setting of advanced
      fibrosis and/or cirrhosis where chronic immune-mediated inflammation over decades
      promotes hepatocyte turnover providing selective pressure that favors the
      malignant phenotype. As well as contributions of unresolved inflammation to
      carcinogenesis, evidence from transgenic mice with liver-specific expression of
      viral sequences suggests that some HCV-encoded proteins may directly promote
      cancer. Numerous in vitro studies suggest roles for HCV proteins in subversion of
      cellular pathways that normally act to suppress tumorigenesis. Here, we review
      the mechanisms by which persistent HCV infection might promote cancer in addition
      to the procarcinogenic effects of inflammatory liver disease.

PMID- 30190969
TI  - Systemic therapy for hepatocellular carcinoma: why do we keep failing?

PMID- 30190970
TI  - Our experts highlight the most important research articles across the spectrum of
      topics relevant to the field of hepatic oncology.

PMID- 30190967
TI  - Current evidence and controversies in the incorporation of biologics for
      metastatic colorectal cancer.
AB  - With the advent of new drugs and therapeutic combinations for metastatic
      colorectal cancer, the prognosis for this often incurable disease is improving.
      In addition to traditional cytotoxic chemotherapeutics, targeted biologic
      therapies, such as cetuximab, panitumumab, bevacizumab, aflibercept and
      regorafenib, are significantly impacting the treatment of this disease. Recent
      investigations have focused on determination of the optimal usage of these
      biologic therapies, but many controversies still exist. Specifically, emerging
      data regarding appropriate combinations of cytotoxics and biologics in each
      metastatic colorectal cancer treatment setting, the superiority of particular
      biologics as single agents or in combination with chemotherapy, dual biologic
      therapy, use of biologics for conversion or maintenance therapies, and predictive
      biomarker discovery for biologics are addressed in this article, as these issues
      are rapidly changing our approach to the treatment of the patient with metastatic
      colorectal cancer.

PMID- 30190971
TI  - Our experts highlight the most important research articles across the spectrum of
      topics relevant to the field of hepatic oncology.

PMID- 30190972
TI  - Addition of bevacizumab to preoperative chemotherapy for colorectal liver
      metastases does not increase perioperative morbidity and mortality.
AB  - Aim: Patients with colorectal liver metastases (CRLM) benefit from liver
      resection. Bevacizumab is commonly used in these patients resulting in a greater
      number of patients receiving an operation for a potentially curative liver
      resection, with initially unresectable liver metastases. Our purpose was to
      evaluate the effect of preoperative bevacizumab administration on perioperative
      complications in patients undergoing hepatic resection for CRLM. Methods: A
      retrospective analysis of patients undergoing hepatic resection for CRLM who
      received only neoadjuvant chemotherapy (chemotherapy group, n = 133), or
      neoadjuvant chemotherapy and bevacizumab (chemotherapy and bevacizumab group, n =
      103). We compared surgical characteristics, perioperative complications and
      postoperative liver function. Results: The type of liver resection (minor vs
      major liver resection) was comparable in the two groups (major liver resection
      52.6 vs 62.1%, p = 0.144). The addition of bevacizumab to preoperative
      chemotherapy does not affect the frequency (chemotherapy group vs chemotherapy
      and bevacizumab group, 35.3 vs 38.8%, p = 0.581), severity (major complications,
      20.3 vs 19.4%, p = 0.487) and type of perioperative complications. Preoperative
      administration of bevacizumab was associated with a higher peak of postoperative
      alanine aminotransferase levels but did not affect functional recovery of the
      liver. Conclusion: Neoadjuvant administration of bevacizumab was not associated
      with an increased risk of postoperative complications after hepatic resection and
      did not affect the liver's functional recovery. Patients receiving more than
      eight cycles of bevacizumab are at an increased risk to develop perioperative
      complications.

PMID- 30190973
TI  - CA 19-9 in combination with abdominal CT scan for the diagnosis of mass-forming
      intrahepatic cholangiocarcinoma.
AB  - Aim: Cholangiocarcinoma (CCA) is a common form of cancer in Thailand. The
      diagnosis of CCA by pathology is widely accepted. Unfortunately, tissue diagnosis
      of mass-forming intrahepatic cholangiocarcinoma is difficult to perform due to
      the risk of the procedure and accessibility. The aim of this study is to assess
      the diagnostic utility of CA19-9 in combination with CT scan for the diagnosis of
      mass-forming cholangiocarcinoma. Materials & methods: The medical records of
      patients with a diagnosis of CCA and hepatocellular carcinoma (HCC) during
      January 2005-December 2009 were reviewed. Only cases with pathology and CT scan
      reports from Maharaj Nakorn Chiang Mai Hospital were included. Demographic data,
      clinical manifestations and laboratory results, including CA19-9 and CT scans of
      the liver, were carefully examined in order to establish their diagnostic utility
      in mass-forming CCA without a pathological diagnosis. Results: A total of 79 CCA
      patients and 66 HCC patients were included in CA19-9 cut-off level analyses. A
      total of 31 CCA patients and 44 HCC patients were included in the CT scan
      evaluation and scored according to the Chiang Mai CT score for CCA. The
      specificity of a CA19-9 value of 500 U/ml for the diagnosis of CCA was 95.5% with
      a sensitivity of 50.6%, positive predictive value of 91.8% and likelihood ratio
      of positive (LR+) of 11.24. A CT score greater than 2 demonstrates a positive
      predictive value of more than 90% in diagnosis of CCA. The CA19-9 level of 140
      U/ml in combination with a CT score of 2 demonstrated LR+ as high as 57.09. A
      CA19-9 level of 280 U/ml in combination with a CT score of 1 demonstrated LR+ of
      58.4. Conclusion: A CA19-9 level combined with the Chiang Mai CT score for CCA
      are good diagnostic tools for the diagnosis of mass-forming cholangiocarcinoma
      with high specificity, high positive predictive value and high likelihood ratio
      of positive.

PMID- 30190974
TI  - Radioembolization with yttrium-90 glass microspheres for patients with
      hepatocellular carcinoma: a review.
AB  - Clinical studies have evaluated the safety and efficacy of radioembolization with
      yttrium-90 in patients with unresectable hepatocellular carcinoma (HCC). Citing
      literature published within the last 5 years, we review the clinical evidence of
      survival outcomes and safety of yttrium-90 treatment in patients with
      unresectable HCC. This paper is primarily focused on survival rates following the
      typical application of yttrium-90 in HCC treatment, and also includes time to
      progression and safety data. Also discussed are special indications and new
      developments related to yttrium-90 therapy in HCC, as well as patient selection
      and its correlation with successful treatment outcomes.

PMID- 30190976
TI  - Liver transplantation for metastatic neuroendocrine tumors.
AB  - Neuroendocrine tumors are a heterogeneous group of rare epithelial tumors. Most
      of them are metastatic at the time of initial diagnosis. Liver transplantation
      (LT) has been proposed in selected patients with diffuse liver involvement.
      Rationale for LT in this indication is based on the frequently indolent nature of
      neuroendocrine tumors, the propensity for liver-only metastasis and the high rate
      of intrahepatic recurrence after resection. However, indications for LT for
      neuroendocrine liver metastases remain controversial, and patient selection
      criteria is still a matter of debate. The aim of this review is to summarize data
      regarding LT for neuroendocrine liver metastases by answering frequently asked
      questions about this issue.

PMID- 30190975
TI  - Predicting recurrence following radiofrequency percutaneous ablation for
      hepatocellular carcinoma.
AB  - Within 5 years after percutaneous ablation of hepatocellular carcinoma, roughly
      70% of patients experience tumor recurrence. Relapses beyond curative options
      affected patients' survival. Ablation shares with resection common predictive
      factors of recurrence as size of the tumor, multinodularity and presence of
      vascular invasion. High serum alpha-fetoprotein level and markers of severity of
      underlying liver disease have also been found to be associated with recurrence
      and even survival. However, predictive values for recurrence of technical
      factors, histopathological and molecular tumors' features have been rarely
      studied. Few comparative studies have shown that ablation techniques impact
      recurrence rates. Moreover, although ablation does not allow analysis of the
      whole tumor, some reports suggest that biopsies allow histopathological and even
      molecular testing of the risk of recurrence.

PMID- 30190979
TI  - Hepatocellular carcinoma risk scores: ready to use in 2015?

PMID- 30190977
TI  - Malignant transformation of hepatocellular adenoma.
AB  - Hepatocellular adenomas carry a risk of malignant transformation. However, little
      is known about the rate of this risk, the predisposing factors, the histological
      and/or immunohistochemical markers and the precursor lesions. Even the
      pathogenesis of malignant transformation itself is poorly understood. This review
      details the current knowledge on the subject.

PMID- 30190980
TI  - The evolving field of intrahepatic cholangiocarcinoma.

PMID- 30190982
TI  - Our experts highlight the most important research articles across the spectrum of
      topics relevant to the field of hepatic oncology.

PMID- 30190978
TI  - Immunotherapy of hepatocellular carcinoma.
AB  - Newer immunotherapy agents may break the barrier that tumors create to evade the
      attack from the immune system. Dendritic cell vaccination has shown encouraging
      clinical activity and a favorable safety profile in advanced tumor stages.
      However, optimal cell maturation status, choice of tumor antigens and route of
      administration have not been established. Single or multiple peptides derived
      from tumor-associated antigens may also be used for cancer vaccination.
      Intratumoral delivery of oncolytic viruses expressing immunostimulating cytokines
      like GM-CSF have produced stimulating clinical results that need further
      verification. But it is probably T-cell checkpoint modulation with monoclonal
      antibodies that has attracted the highest expectations. Promising activity has
      been reported for tremelimumab, a CTLA-4 inhibitor, and a clinical trial testing
      the PD-1 antibody nivolumab is underway. Future progress will probably come from
      a better understanding of the mechanisms of cancer-related immunosuppression,
      improvement in agents and strategies and combination of the available therapeutic
      tools.

PMID- 30190981
TI  - Implementation of systems theory in liver cancer research.

PMID- 30190983
TI  - Immune play: defending the liver.

PMID- 30190984
TI  - Liver transplantation for advanced hepatocellular carcinoma: how far can we go?
AB  - Liver transplantation is one of the most effective treatment options for
      hepatocellular carcinoma. Although the Milan criteria have been widely used to
      identify suitable candidates for liver transplant with a good prognosis, many
      transplant centers have developed and actually used more expanded criteria.
      Living donor liver transplant (LDLT) is at the center of expansion of criteria
      because it is based on the personal relationship between a recipient and a donor.
      Asian LDLT centers have developed various expanded criteria for LDLT using tumor
      biologic markers as well as the size and number of the tumors. However, there is
      no consensus on the limit of the expansion of criteria. Here, we present our
      experience and opinion on LDLT for advanced hepatocellular carcinoma.

PMID- 30190986
TI  - Contrast-enhanced ultrasound in liver cancer.
AB  - Contrast-enhanced ultrasound (CEUS) is a sure, noninvasive, repeatable imaging
      technique widely used in the characterization of benign and malignant liver
      lesions. The European Federation of Societies for Ultrasound in Medicine and
      Biology guidelines suggest the typical CEUS features of liver lesions as criteria
      for the noninvasive diagnosis in cirrhotic and not-cirrhotic patients. The
      clinical application of CEUS in the liver study is summarized in this review; the
      contrast-enhanced patterns of the most frequent liver lesions are described
      (hepatocellular and cholangiocellular carcinoma, liver metastases, hemangioma,
      focal nodular hyperplasia, adenoma). The role of this imaging technique in the
      diagnostic algorithm of liver malignancy is illustrated and the CEUS application
      in hepatologic and oncological settings is depicted.

PMID- 30190985
TI  - Nonsurgical multidisciplinary approach for recurrent hepatocellular carcinoma
      after surgical resection.
AB  - Hepatocellular carcinoma (HCC) is characterized by frequent recurrence, even
      after curative resection and local ablation, and this represents a major
      challenge for HCC treatment. Although several treatment guidelines have been
      reported, they detail initial treatment choices and there are no established
      guidelines for recurrent HCC. The current treatment options for recurrent HCC do
      not differ from the primary treatments, but the unique characteristics of HCC
      recurrence should be considered when choosing treatments and each treatment
      should be individualized to different clinical situations. Furthermore,
      combinations of various treatments have been recently attempted. This review
      summarizes the current evidence for nonsurgical treatments of recurrent HCC after
      resection and suggests a multidisciplinary approach to improving the prognosis of
      recurrent HCC.

PMID- 30190989
TI  - Resection versus ablation for hepatocellular carcinoma: role of initial
      treatment.

PMID- 30190988
TI  - The efficacy and effectiveness of hepatocellular carcinoma surveillance in
      patients with cirrhosis.

PMID- 30190990
TI  - Screening and treatment of hepatitis B virus to prevent liver cancer in Africa.

PMID- 30190991
TI  - Laser ablation: an alternative to radiofrequency ablation for hepatocellular
      carcinoma in cirrhotic patients?

PMID- 30190987
TI  - Genetic risk markers for hepatocellular carcinoma in patients with alcoholic
      liver disease.
AB  - Various single nucleotide polymorphisms have been reported to be associated with
      a higher risk of hepatocellular carcinoma in alcoholic cirrhotic patients. Until
      now, only common variants conferring a small increase in liver cancer risk have
      been identified. These inherited factors are able to modulate several biological
      pathways involved in alcohol-induced hepatocarcinogenesis, such as ethanol
      metabolism, inflammation, oxidative stress, or iron and lipid homeostasis. How
      the combination of these variants might collectively define an individual genomic
      risk prediction is currently being investigated. The other challenge in clinical
      practice lies in defining how to integrate this genetic information with other
      clinical parameters so as to refine selection of alcoholic cirrhotic patients
      according to various classes of hepatocellular carcinoma risk.

PMID- 30190992
TI  - Radioembolization for hepatocellular carcinoma: current role and future
      directions - the medical oncologist's perspective.
AB  - The incidence and impact of hepatocelluar carcinoma (HCC) continues to increase
      worldwide. While radical therapies such as resection, radiofrequency ablation or
      transplantation are potentially curative for patients with early-stage HCC, the
      majority of patients in routine practice present with more advanced tumors, where
      treatment goals are palliation and extending survival. With multiple new and
      promising treatment options emerging for these patients, the challenge for the
      medical oncologist is how best to integrate these therapies into routine clinical
      practice. Here we review the most recent data on the efficacy and safety of
      yttrium-90 radioembolization in HCC, the considerations involved in patient
      selection, and the optimal assessment and management of patients receiving
      treatment. We also examine the potential impact of several ongoing clinical
      trials.

PMID- 30190993
TI  - Radiotherapy for liver tumors.
AB  - Many patients with primary hepatic malignancies present with advanced disease
      that is not suitable for surgical resection, orthotopic liver transplantation, or
      radiofrequency ablation. Outcomes are particularly dismal in patients with large,
      unresectable tumors and/or tumor venous thrombosis. Liver-directed radiotherapy,
      including stereotactic body radiotherapy (SBRT), is able to treat a variety of
      tumor sizes and tumors with venous involvement and has demonstrated excellent
      safety and control outcomes. SBRT should be considered a standard option in
      patients with early-stage hepatocellular carcinoma who are not candidates for
      surgical resection, orthotopic liver transplantation or radiofrequency ablation.
      SBRT should be strongly considered in patients with larger tumors and/or tumors
      with tumor venous thrombosis who have adequate liver function. Radiotherapy
      should remain a focus of hepatocellular carcinoma research.

PMID- 30190994
TI  - Chemoembolization of hepatocellular carcinoma with HepaSphereTM.
AB  - This review discusses the current data on HepasphereTM in the treatment of
      hepatocellular carcinoma. HepaSphere is a drug-loadable microsphere that can be
      bound with doxorubicin, epirubicin, cisplatin or oxaliplatin. In vitro and in
      vivo studies confirm lower systemic exposure to the drug and fewer systemic
      doxorubicin-related side effects. Studies suggest that this technique is better
      tolerated than conventional lipiodol-based chemoembolization (c-TACE). In
      intermediate and early stage hepatocellular carcinoma - nonresponsive to curative
      treatments - complete response and partial response rates range from 22.2 to 48%
      and 43.7 to 51%, respectively. Studies with survival as an end-point are needed
      and head-to-head comparisons with other drug-eluting beads are necessary.

PMID- 30190995
TI  - A role for hepatic surgery in patients with liver metastatic breast cancer:
      review of literature.
AB  - Traditionally, patients with metastatic breast cancer were seen as carrying a
      grim prognosis and therapy was based mainly on palliative chemotherapy and
      hormonal therapy, with surgery being considered as ineffective. However, in the
      last 20 years different centers worldwide published series of metastatic breast
      cancer patients who underwent resection for different metastatic sites (liver,
      brain, lung), reporting favorable results. Most of these papers addressed to the
      role of liver surgery in patients with breast cancer liver metastases, mainly due
      to the favorable results achieved by liver resection in patients with metastatic
      colorectal cancer. In this review are presented the results achieved by liver
      surgery in patients with breast cancer liver metastases.

PMID- 30190996
TI  - Hepatocellular adenoma management: advances but still a long way to go.
AB  - Hepatocellular adenomas (HCAs) are composed of four molecular subgroups:
      mutations inactivating the HNF1A gene; the inflammatory phenotype with mutations
      of different genes leading to STAT3 activation; the activation of beta-catenin by
      mutations in exon 3; among beta-HCA, half display both inflammatory and beta
      catenin-activated phenotypes; and the unclassified tumors. The identification of
      these subtypes by MRI and immunohistochemistry on tissue is considered as a major
      criterion to manage patients. Of particular relevance is the identification of
      the beta-catenin-mutated group due to its high risk of malignant transformation.
      In spite of this progress, the classification has not gained recognition among
      surgeons. It is hoped that by working as a multidisciplinary team, including
      surgeons, radiologists, pathologists and molecular biologists, patients will be
      managed more rationally. In this article, we will present known and new data,
      well accepted and that which is still controversial. The progress made in the
      field of HCA in the last 12 years, whether in epidemiology, diagnosis (clinical,
      pathology, imaging) or management, is related in one way or another to molecular
      advances.

PMID- 30190997
TI  - Liver transplantation in treatment of colorectal liver metastases.
AB  - Surgical resection is the only curative modality for colorectal liver metastases
      (CLM) and 5-year overall survival after resection is about 40%. Nonresectable CLM
      is not curable and 5-year overall survival is currently about 10%. Before 1995,
      several liver transplantations for CLMs were performed, but outcome was poor (5
      year survival rate: 18%). Liver transplantation for CLMs was abandoned and CLMs
      were even considered a contraindication to the procedure. Since then, the
      survival rate after liver transplantation in general has improved by almost 30%.
      In a prospective pilot study of liver transplantation for nonresectable CLM, a 5
      year overall survival rate of 60% was demonstrated, however 19 of 21 patients
      experienced recurrence of disease. Here, current knowledge and ongoing research
      in this field is reviewed, and the potential role for liver transplantation as
      one of several treatment modalities for CLM discussed.

PMID- 30190999
TI  - Systemic chemotherapy with oxaliplatin is a good option for advanced
      hepatocellular carcinoma.

PMID- 30190998
TI  - The emerging role of positron emission tomography in hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality worldwide.
      HCC a heterogeneous disease occurring on the background of cirrhosis. The
      presence of cirrhosis limits the sensitivity of conventional imaging modalities
      in differentiating HCC from surrounding cirrhotic parenchyma. Positron emission
      tomography (PET) using 18F-fluorodeoxyglucose (18F-FDG) is widely used for
      assessing a variety of malignancies, however, has poor sensitivity in the
      evaluation of HCC. This has led to the investigation of other radiotracers such
      as 11C-acetate and 11C-choline, with improved sensitivity in terms of detection
      and therapeutic response. In this review, we discuss the emerging field of PET
      imaging for the detection, staging and assessment of treatment response in HCC.
      In particular we discuss the role of 18F-FDG-PET in imaging hepatocellular
      cancer, the limitations of this PET tracer and emerging novel PET tracers being
      investigated that exploit key metabolic processes including fatty acid and lipid
      synthesis, choline kinase activity and gene expression.

PMID- 30191000
TI  - How endoplasmic reticulum stress contributes to obesity-driven hepatic
      tumorigenesis.

PMID- 30191003
TI  - The changing etiology of liver cancer.

PMID- 30191001
TI  - Isoform-specific activation of Akt involvement in hepatocarcinogenesis.

PMID- 30191002
TI  - Our panel of experts highlight the most important research articles across the
      spectrum of topics relevant to the field of hepatic oncology.

PMID- 30191004
TI  - Surveillance for hepatocellular carcinoma in chronic hepatitis B virus infection:
      for whom.

PMID- 30191005
TI  - High level of serum protein DKK1 predicts poor prognosis for patients with
      hepatocellular carcinoma after hepatectomy.
AB  - Aim: To evaluate prognostic significance of DKK1 for hepatocelluar carcinoma.
      Materials & methods: We enrolled a test cohort consisting of 266 hepatitis virus
      B-related hepatocelluar carcinoma patients who had undergone hepatectomy and a
      validation cohort of 95. Associations of DKK1 with overall survival and time to
      recurrence were determined by Cox proportional hazards regression model. Results:
      High levels of preoperative serum DKK1 were associated with poor overall survival
      and higher recurrence rate and DKK1 was an independent prognostic predictor.
      Moreover, DKK1 maintained ability to predict recurrence for patients with low
      recurrence risk. Double positives of DKK1 and AFP indicated the worst overall
      survival and the highest recurrence rate compared with either used alone.
      Patients with preoperatively and 1-day postoperatively positive DKK1 had higher
      recurrence rates than those whose values were both negative. Similar results were
      found in the validation cohort. Conclusion: Serum DKK1 could predict prognosis of
      hepatocelluar carcinoma after hepatectomy.

PMID- 30191006
TI  - Surgical treatment of hepatocellular carcinoma: should resection be performed
      according to Barcelona Clinic Liver Cancer classification?
AB  - The best results in surgical resection are obtained in patients with solitary
      tumors without clinically significant portal hypertension (hepatic venous
      pressure gradient >10 mmHg). In such settings, 5-year survival rates exceed 70%.
      When portal hypertension exceeds this cut-off value, 5-year survival decreases to
      55%, as is also the case in patients with more than one nodule. Surgery may be
      technically feasible, in other words, with acceptable 30-day mortalities although
      the clinically relevant survival outcome is significantly reduced. In such
      instances, patients may be better served by liver transplantation. If this option
      is not available, the outcome may not differ to that obtained by ablation for
      small solitary hepatocellular carcinoma or for chemoembolization for those
      patients with multifocal hepatocellular carcinoma within the Milan criteria. This
      philosophy is the backbone for the Barcelona Clinic Liver Cancer decision-making
      process.

PMID- 30191007
TI  - Biphenotypic (hepatobiliary) primary liver carcinomas: the work in progress.
AB  - Recent WHO classification for combined hepatocellular-cholangiocarcinoma and
      recognized stem cell subtypes has increased attention to such tumors; however,
      the resulting burst of reporting and research indicates that this classification,
      while provocative, is incomplete for description of the full array of primary
      liver carcinomas with biphenotypic (hepatobiliary) differentiation. We review the
      history of such lesions and consider the wider array of such tumors previously
      described. Mixed hepatobiliary phenotypes and immunophenotypes are found in
      individual tumors at the tissue level - with architectural and cytologic features
      supportive of both differentiation states - and at the cellular level, with
      individual cells that display cytology of one cell type, but immunophenotypically
      showing mixed expression. Pathobiologic and clinical questions to be answered by
      future research are suggested.

PMID- 30191008
TI  - Hepatic arterial infusional chemotherapy in the management of colorectal cancer
      liver metastases.
AB  - Colorectal liver metastases (CRLM) receive their blood supply predominantly
      through the hepatic artery. Intra-arterial drug delivery can optimize the dose
      and time exposure of chemotherapy to tumor cells while limiting systemic
      toxicity. Chemotherapy is most commonly administered through a catheter
      surgically placed in the gastroduodenal artery and connected to a subcutaneous
      pump. Due to its pharmacokinetics features, floxuridine is the most commonly used
      drug in the USA with hepatic arterial infusional (HAI) chemotherapy. To date,
      many clinical trials have shown the positive impact of HAI in the management of
      CRLM. Hence, in unresectable patients, HAI is associated with high response rates
      and commonly enables subsequent resection in both chemonaive and previously
      treated patients. Outcomes in patients converted to complete resection are
      similar to patients who present with initially resectable disease. In the
      adjuvant setting, HAI with floxuridine improves survival as well as hepatic and
      overall disease-free survival after complete resection of CRLM, as compared with
      5-FU alone, in three of four randomized studies. To date, no trials have compared
      HAI combined with modern chemotherapy alone to modern chemotherapy alone in the
      adjuvant setting.

PMID- 30191011
TI  - DNA methylation in hepatocellular carcinoma: what is the use?

PMID- 30191009
TI  - Current issues on genomic heterogeneity in hepatocellular carcinoma and its
      implication in clinical practice.
AB  - Hepatocellular carcinoma (HCC) is a highly heterogeneous disease leading to a
      major diversity. Since staging systems are used in patient care, molecular and
      histopathological features remain to be incorporated in management algorithms.
      HCC, as other malignant solid tumors, exhibit a complex genetic diversity and
      genomic instability, driving tumorigenesis. The recent development of deep
      sequencing techniques has revealed different subgroups of tumors defined by
      specific patterns of genomic alterations that are related to clinical and
      histopathological diversity in HCC. Additionally, several genomic defects
      identified in HCC will be used in the future to develop clinical trial design for
      tumorized treatment.

PMID- 30191010
TI  - The search for precision models clinically relevant to human liver cancer.

PMID- 30191012
TI  - The impact of intraoperative ultrasonography on the management of disappearing
      colorectal liver metastases.

PMID- 30191013
TI  - Hepatic stem cells and cancers: a pathologist's view.
AB  - Neil Theise speaks to Georgia Patey, Commissioning Editor: Neil Theise is a
      diagnostic liver pathologist, adult stem cell researcher and complexity theorist
      in New York City, where he is a Professor of Pathology at the Mount Sinai Beth
      Israel Medical Center of Icahn School of Medicine at Mount Sinai. He received his
      medical degree from Columbia University College of Physicians and Surgeons, where
      he also received his training in Anatomic Pathology. Subspecialty training was
      pursued in gastrointestinal (NYU), liver (Royal Free Hospital) and liver
      transplant (Mount Sinai, NYC) pathology. His earliest research focus was on
      defining the premalignant dysplastic nodules in human chronic liver disease. He
      revised understandings of human liver microanatomy, which in turn, led directly
      to identification of possible liver stem cell niches and the marrow-to-liver
      regeneration pathway. He is considered a pioneer of multiorgan adult stem cell
      plasticity. His publications on these topics in model systems and human liver
      stem cells have been highlighted on a record five covers of Hepatology.

PMID- 30191014
TI  - Radioembolization as an adjunct therapy to the resection of liver tumors.

PMID- 30191015
TI  - Role of ablation: should it be used as primary therapy for early-stage
      hepatocellular carcinoma?

PMID- 30191016
TI  - Aggressive systemic mastocytosis of the liver with cholangitis.
AB  - Mastocytosis is a clonal, neoplastic mast cell proliferation, which is in most
      cases restricted to the skin (cutaneous mastocytosis), but may infiltrate other
      organs as well (systemic mastocytosis). Involvement of the liver by a systemic
      mastocytosis with impairment of liver function has been recognized as sign of an
      aggressive course of disease (C-finding). This article presents a case of
      aggressive systemic mastocytosis in a 26-year-old male patient with involvement
      of the liver mimicking primary sclerosing cholangitis. By histology we could
      demonstrate multifocal clusters of atypical mast cells infiltrating portal tracts
      in intimate contact with bile ducts as the cause of cholangitis and liver
      fibrosis.

PMID- 30191017
TI  - New horizons in ablation therapy for hepatocellular carcinoma.
AB  - Historically ablative treatment for hepatocellular cancer (HCC) has been regarded
      as inferior to transplantation and resection and has therefore been reserved for
      patients not suitable for surgical intervention in stage 0-A HCC according to the
      Barcelona Clinic Liver Cancer classification system. In the wake of surgical
      strategies challenging the current Barcelona Clinic Liver Cancer treatment
      guidelines and improvements in imaging, targeting and ablation technologies,
      ablation is likely to occupy a more central role in the management of patients
      with HCC, challenging its historically perceived inferiority to resection.

PMID- 30191018
TI  - Next-generation sequencing and personalized genomic medicine in hepatobiliary
      malignancies.
AB  - Liver cancer is a heterogeneous group of tumors characterized by significant
      molecular and genomic heterogeneity. The advent of powerful genomic technologies
      has allowed detection of recurrent somatic alterations in liver cancer, including
      mutations, copy number alterations as well as changes in transcriptomes and
      epigenomes, with the potential to translate these data into clinically relevant
      predictive and prognostic factors. In this review, we discuss recent advances in
      the application of high-throughput genomic technologies in liver cancer and the
      integration of such cancer genome profiling data, highlighting specific relevant
      subgroups and explain how this knowledge can be used in translational clinical
      research, 'basket trials', molecular tumor boards, targeted therapy and for
      personalized genomic medicine applications.

PMID- 30191021
TI  - Hepatocellular carcinoma: asphyxiate and then cook.

PMID- 30191020
TI  - Liver transplantation in the management of perihilar cholangiocarcinoma.
AB  - Cholangiocarcinoma (CCA) is the second most common primary hepatic neoplasm and
      accounts for 10-20% of hepatobiliary cancer-related deaths. The prognosis of
      patients with CCA is poor with 5-year survival rates of 10%, partially due to the
      limited effective treatment options that exist for this disease. In this review,
      we discuss the evolving role of liver transplantation in the management of
      patients with perihilar CCA (pCCA). We specifically discuss the Mayo Clinic
      protocol of neoadjuvant chemoradiation followed by liver transplantation in
      selected patients with pCCA and describe pretransplant, peritransplant, and post
      transplant considerations and challenges with this approach. Finally, we review
      local, national and international outcomes and discuss future directions in
      optimizing this treatment strategy for patients who otherwise have few
      therapeutic options and limited survival.

PMID- 30191022
TI  - Selected summary for the 2015 Asia-Pacific Primary Liver Cancer Expert Meeting
      (APPLE).
AB  - Liver cancer is now ranked second in terms of cancer-related mortality worldwide;
      with limited treatment options for patients at advanced stages it remains a
      growing health problem. All Phase III clinical trials testing molecular therapies
      after sorafenib have so far failed, and there is still not a validated oncogene
      addiction loop. Despite the present huge challenges, advancements in the recent
      years have been remarkable. The Asia-Pacific Primary Liver Cancer Expert Meeting
      (APPLE) was designed to promote scientific exchanges of international and
      regional experts in the study and management of liver cancer. Over the years it
      has consolidated as a major resource to provide a thorough update to clinicians
      and researchers located in the Asia-Pacific region in different aspects of liver
      cancer. Attendance at these meetings is exceptional, with an average of 1000
      attendees at each conference. As predicted, the 2015 edition provided an
      outstanding overview of the latest developments in the clinical management and
      molecular pathogenesis of the disease.

PMID- 30191019
TI  - Apoptosis in liver carcinogenesis and chemotherapy.
AB  - Hepatocellular carcinoma (HCC) is a major health problem. In human
      hepatocarcinogenesis, the balance between cell death and proliferation is
      deregulated, tipping the scales for a situation where antiapoptotic signals are
      overpowering the death-triggering stimuli. HCC cells harbor a wide variety of
      mutations that alter the regulation of apoptosis and hence the response to
      chemotherapeutical drugs, making them resistant to the proapoptotic signals.
      Considering all these modifications found in HCC cells, therapeutic approaches
      need to be carefully studied in order to specifically target the antiapoptotic
      signals. This review deals with the recent relevant contributions reporting
      molecular alterations for HCC that lead to a deregulation of apoptosis, as well
      as the challenge of death-inducing chemotherapeutics in current HCC treatment.

PMID- 30191023
TI  - The 9th Annual Conference of the International Liver Cancer Association (ILCA)
      2015.
AB  - The 9th International Liver Cancer Association Annual Conference was held from
      4th to 6th September 2015 in Paris, France, and attracted a record breaking 900
      participants from 51 different countries and 386 submitted abstracts from
      scientists around the globe. The congress provided a comprehensive overview of
      current developments in primary liver cancers (i.e., hepatocellular carcinoma and
      cholangiocarcinoma) and covered a broad range of topics from basic science to
      clinical studies. Following the success of immunotherapies in recent years, a
      preconference workshop on immunopathogenesis and immunotherapy in hepatocellular
      carcinoma also took place. This report will provide a subjective summary of
      selected abstracts presented at the conference.

PMID- 30191024
TI  - Liver cancer screening in high-risk populations.
AB  - Patients with liver disease have a risk of developing hepatocellular carcinoma
      (HCC), but the risk varies between different diseases and is also different
      according to several other variables, such as age, type of underlying liver
      disease and severity of disease. Several risk scores have been developed to more
      adequately quantitate HCC risk in individual patients. Each risk score is
      applicable to a specific population (chronic hepatitis B or C, patients on the
      transplant list, cirrhosis in general, and so on). Most publications on risk
      scores do not provide clear guidance as to what level of measured risk is
      sufficient to trigger surveillance.

PMID- 30191027
TI  - Progression of systemic chemotherapy with oxaliplatin-containing regimens for
      advanced hepatocellular carcinoma in China.
AB  - Hepatocellular carcinoma (HCC) characterized by insidious onset is a highly
      invasive malignance and has a rapid progress. The majority of patients,
      especially in Asian countries, present with locally advanced or distant
      metastatic disease at diagnosis and are not eligible for local treatment. Before
      the publication of the EACH study results showing the survival benefits of the
      FOLFOX 4 regimen in Chinese patients with advanced HCC, no chemotherapeutical
      drug or regimen was considered as systemic chemotherapy standard for this group
      of patients due to the lack of evidence-based recommendations. Oxaliplatin
      containing regimens have shown clinical activity against advanced HCC with an
      acceptable safety profile. The aim of this article is to present a review of the
      scientific evidence mainly originating from China that supports the
      recommendation of oxaliplatin-based regimens for the treatment of Chinese
      patients with advanced HCC.

PMID- 30191025
TI  - Role of alcohol in the development and progression of hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is a significant cause of cancer-related morbidity
      and mortality. Chronic, heavy ethanol consumption is a major risk for developing
      the worsening liver pathologies that culminate in hepatic cirrhosis, the leading
      risk factor for developing HCC. A significant body of work reports the
      biochemical and pathological consequences of ethanol consumption and metabolism
      during hepatocarcinogeneis. The systemic effects of ethanol means organ system
      interactions are equally important in understanding the initiation and
      progression of HCC within the alcoholic liver. This review aims to summarize the
      effects of ethanol-ethanol metabolism during the pathogenesis of alcoholic liver
      disease, the progression toward HCC and the importance of ethanol as a comorbid
      factor for HCC development.

PMID- 30191026
TI  - The clinical role of 'liquid biopsy' in hepatocellular carcinoma.
AB  - Circulating free tumor DNA (ctDNA) is DNA released from necrotic or apoptotic
      tumor cells into the bloodstream. Absolute levels of ctDNA, as well as genetic
      mutations and epigenetic changes detected in ctDNA are useful biomarkers of tumor
      biology, progression and response to therapy in many tumor types and recent
      evidence suggests they may be useful in hepatocellular carcinoma (HCC). ctDNA
      detected in blood, therefore, offers a minimally invasive, easily repeated
      'liquid biopsy' of cancer, providing real-time dynamic analysis of tumor behavior
      and treatment response that could revolutionize both clinical and research
      practice in HCC. In this review, we provide a critical summary of the evidence
      for the utility of ctDNA as a diagnostic and prognostic biomarker in HCC.

PMID- 30191028
TI  - Epidemiology and surgical management of intrahepatic cholangiocarcinoma.
AB  - Intrahepatic cholangiocarcinoma (ICC) is a rare hepatobiliary malignancy arising
      from the epithelial cells of the intrahepatic bile ducts. The increased incidence
      of ICC worldwide may reflect both a true increase and the earlier detection of
      the disease. Despite the advances in modern surgical care, the curative chance
      for ICC remained suboptimal: tumor-free margins are hard to achieve due to tumor
      locations, and technical challenges and recurrence, either local or distant, may
      hamper the resectability in a large number of patients. Lymph node involvement
      and vascular invasions are considered negative predictive factors for survival of
      ICC patients. This review discusses the epidemiology, risk factors and surgical
      management of ICCs, and mainly focuses on outcomes and factors associated with
      surgical treatment.

PMID- 30191029
TI  - Neoadjuvant treatment of biliary tract cancer: state-of-the-art and new
      perspectives.
AB  - Gall bladder cancer (GBC), and intrahepatic and extrahepatic (perihilar or distal
      bile duct's) cholangiocarcinomas (CCA) are usually diagnosed in locally advanced
      or node-positive stage, with a short survival rate. Thus, it appears essential to
      explore novel strategies for improving disease downstage and radical surgery.
      Chemoradiotherapy followed by liver transplantation seems to be one of the most
      promising approaches for intrahepatic or perihilar disease while chemotherapy
      with novel radiotherapy techniques (such stereotactic body radiation) emerged as
      an attractive preoperative treatment in distal diseases. In this paper, we will
      review currently available knowledge about neoadjuvant treatment of biliary tract
      cancers (BTC) paying attention to challenges that make this type of management in
      clinical practice difficult.

PMID- 30191030
TI  - Identifying patients at risk from nonalcoholic fatty liver-related hepatocellular
      carcinomas.

PMID- 30191031
TI  - What are the options for hepatocellular carcinoma patients who progress under
      sorafenib?

PMID- 30191033
TI  - Comparative analysis of current guidelines for the treatment of hepatocellular
      carcinoma.
AB  - Hepatocellular carcinoma is one of the most common malignancies and represents a
      unique challenge for physicians and patients. Treatment patterns are not uniform
      between areas despite efforts to promote a common protocol. Even if most
      hepatologists worldwide adopt the Barcelona Clinic Liver Cancer staging system,
      Asian and North American physicians are also independently making an effort to
      expand the indications of each treatment, combining therapies for better
      outcomes. Also, new therapeutic techniques have emerged and an increasing number
      of studies are trying to include these paradigm shifts into newer treatment
      guidelines. Controversial and diverging points in the current international
      guidelines are emphasized and discussed. Unanswered questions are also analyzed
      to identify the most needed and promising future perspectives.

PMID- 30191032
TI  - Advances in transarterial therapies for hepatocellular carcinoma: is novel
      technology leading to better outcomes?
AB  - Conventional transarterial chemoembolization (c-TACE) was validated in 2002 for
      intermediate stage hepatocellular carcinoma (HCC). Recent improvements in overall
      survival after c-TACE in HCC is linked to both better patient selection, and
      improvement in treatment technologies: catheter, image guidance and new drug
      delivery platforms. Drug eluting beads (DEBs) demonstrated a benefit over c-TACE
      in pharmacokinetic studies; however, two randomized studies comparing c-TACE and
      DEB-TACE demonstrated no benefit of DEB-TACE in response rate or overall
      survival. Delivery platforms loaded with yttrium-90 deliver selective internal
      radiation therapy, which opens a new field of therapy for HCC. Future improvement
      in intra-arterial therapies will include resorbable loadable embolic material,
      new emulsion used for c-TACE and platforms releasing multikinase inhibitors.

PMID- 30191034
TI  - Functional imaging of hepatocellular carcinoma.
AB  - Imaging plays a key role in the clinical management of hepatocellular carcinoma
      (HCC), but conventional imaging techniques have limited sensitivity in
      visualizing small tumors and assessing response to locoregional treatments and
      sorafenib. Functional imaging techniques allow visualization of organ and tumor
      physiology. Assessment of functional characteristics of tissue, such as
      metabolism, proliferation and stiffness, may overcome some of the limitations of
      structural imaging. In particular, novel molecular imaging agents offer a
      potential tool for early diagnosis of HCC, and radiomics may aid in response
      assessment and generate prognostic models. Further prospective research is
      warranted to evaluate emerging techniques and their cost-effectiveness in the
      context of HCC in order to improve detection and response assessment.

PMID- 30191035
TI  - Controversies of preoperative portal vein embolization.
AB  - Portal vein embolization (PVE) is a safe, percutaneous procedure that has been
      proven to lower the complication rates of curative intent large-volume hepatic
      resection by inducing hypertrophy of the future liver remnant. While the safety
      and efficacy of PVE has been well substantiated, there remains controversy with
      regards to the technical details, periprocedural management, and whether
      alternative methods of achieving future liver remnant hypertrophy are preferable
      to PVE. This paper will address those controversies and offer recommendations
      based on available data.

PMID- 30191037
TI  - Erratum.
AB  - [This corrects the article DOI: 10.2217/hep.15.36.].

PMID- 30191038
TI  - Hepatocellular carcinoma and immune therapy, from a clinical perspective; where
      are we?

PMID- 30191036
TI  - The role of miRNAs in cholangiocarcinoma.
AB  - Cholangiocarcinoma (CCA) is a devastating malignancy with high mortality, in part
      due to the combination of late presentation, significant diagnostic challenges
      and limited effective treatment options. Late presentation and diagnosis
      contribute to the high mortality in CCA and there is an urgent unmet need for
      diagnostic and prognostic biomarkers to facilitate early diagnosis and treatment
      stratification to improve clinical outcomes. MiRs are small ncRNA molecules that
      regulate gene expression and modulate both tumor suppressive and oncogenic
      pathways. They have a well-defined role in carcinogenesis, including CCA. In this
      review, we outline the evidence for MiRs in the pathogenesis of CCA and their
      potential utility as diagnostic and prognostic biomarkers to guide clinical
      management.

PMID- 30191040
TI  - Insights into the SIRFLOX study.
AB  - Peter Gibbs speaks to Laura Dormer, Editorial Director: Peter Gibbs is a medical
      oncologist at the Western and Royal Melbourne Western Hospitals (Australia), and
      a laboratory head at the Walter and Eliza Hall Institute (Australia). He has a
      particular interest in translational research related to prognostic and
      predictive biomarkers for colorectal cancer. He is also heavily involved in
      clinical research, including being lead investigator of multiple international
      Phase III trials. He leads several national and international cancer registries,
      capturing comprehensive treatment and outcome data for patients treated in
      routine clinical care.

PMID- 30191039
TI  - Regorafenib and the RESORCE trial: a new second-line option for hepatocellular
      carcinoma patients.
AB  - Dr Jordi Bruix* speaks to Laura Dormer, Editorial Director: Dr Jordi Bruix is the
      Head of the Barcelona Clinic Liver Cancer (BCLC) group at the Hospital Clinic
      (University of Barcelona, Spain) and Director of the Network for Research in
      Liver and Digestive Disease (CIBEREHD) in the Spanish Research Institute. His
      research has changed the diagnosis and treatment of liver cancer. Major
      highlights include: development of the BCLC staging and treatment; development of
      diagnostic criteria for hepatocellular carcinoma; identification of the value of
      portal pressure in predicting prognosis after resection; and acting as principal
      investigator of the Phase III trials that have shown the benefits of
      chemoembolization, sorafenib and regorafenib for patients with liver cancer. He
      has authored the European Assoaciation for the Study of the Liver, American
      Association for the Study of Liver Diseases and World Gastroenterology
      Organization Practice Guidelines and the United Network for Organ Sharing
      hepatocellular carcinoma (HCC) diagnostic criteria.

PMID- 30191041
TI  - RFA plus lyso-thermosensitive liposomal doxorubicin: in search of the optimal
      approach to cure intermediate-size hepatocellular carcinoma.
AB  - When heated during a radiofrequency ablation (RFA) procedure to >=40 degrees C,
      lyso-thermosensitive liposomal doxorubicin (LTLD) produces high drug
      concentration in the surrounding margins of the ablation zone. The hypothesis
      that the RFA + LTLD combination can effectively treat hepatocellular carcinoma
      (HCC) was investigated in the HEAT study: adding LTLD did not improve the
      efficacy of normal practice RFA. However, among the 285 patients with a solitary
      lesion who received at least 45-min RFA dwell time, the hazard ratio for overall
      survival was 0.63 (95% CI: 0.41-0.96; p = 0.04). The OPTIMA study is currently
      ongoing to test the hypothesis that adding LTLD to a standardized RFA lasting
      >=45 min increases survival compared with standardized RFA alone.

PMID- 30191043
TI  - The next generation of hepatocellular cancer experts: what do they think?

PMID- 30191042
TI  - Immune checkpoint inhibitors for hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is a leading cause of cancer deaths worldwide, and
      advanced HCC generally caries a poor prognosis. The treatment of advanced disease
      is limited to sorafenib, which provides only a limited improvement in survival,
      and novel therapies are, thus, sorely needed. Among emerging alternative
      approaches, immune checkpoint inhibitors are a particularly promising treatment
      modality. In this review, we summarize current knowledge of the mechanisms for
      the two primary targets of immune checkpoint inhibitors and discuss the relevance
      of these pathways to the immunology of HCC. We also review the state of ongoing
      and forthcoming trials of immune checkpoint blockade in HCC.

PMID- 30191044
TI  - Pathway of care of hepatocellular carcinoma in 2017.

PMID- 30191047
TI  - Fibroblast growth factor 19, a double-edged sword.

PMID- 30191048
TI  - Retrotransposons and genetic instability in hepatocellular carcinoma.

PMID- 30191045
TI  - Monitoring outcomes in intrahepatic cholangiocarcinoma patients following hepatic
      resection.
AB  - Intrahepatic cholangiocarcinoma (iCCA) is one of the fatal gastrointestinal
      cancers with increasing incidence and mortality. Although surgery offers the only
      potential for cure in iCCA patients, the prognosis is not optimal with low
      overall survival rate and high disease recurrence. Hence, adjuvant therapy is
      generally recommended in the management of high-risk patients. Identifying
      factors associated with disease recurrence and survival of the iCCA patients
      after resection will improve understanding of disease prognosis and help in
      selecting patients who will benefit from surgical resection or stratifying them
      for clinical trials. Despite development of new methods for early detection of
      tumor recurrence, effective prognostic models and nomograms, and recent advances
      in management, significant challenges remain in improving the prognosis of iCCA
      patients.

PMID- 30191049
TI  - Exploring liver physiology, pathology, TGF-beta, EMT, stemness and new
      developments in liver cancer.
AB  - Isabel Fabregat speaks to Roshaine Wijayatunga, Managing Commissioning Editor.
      Isabel Fabregat, PhD, is Senior Investigator, Head of the group "TGF-beta and
      cancer", at the Bellvitge Biomedical Research Institute (IDIBELL) and Associate
      Professor in the School of Medicine and Health Sciences at the University of
      Barcelona. She is the President of the Spanish Society for Cell Biology since
      2011, she was member of the Executive Board of the Spanish Branch of the European
      Tissue Culture Society and she is currently member of the Spanish Society for the
      Study of the Liver, and the International Liver Cancer Association, among others.
      The current research line of her laboratory focuses on the dissection of the
      molecular mechanisms induced by TGF-beta in liver cells that can explain its
      different, and sometimes opposite, functions in liver pathologies, in particular
      fibrosis and hepatocarcinogenesis. Cross-talk between TGF-beta and other
      pathways, in particular EGFR signaling, is also one of the current interests of
      the lab. From October 2012 she has coordinated an Initial Training Network -
      Marie Curie European Action that under the acronym of 'IT-LIVER' (Inhibiting TGF
      beta in Liver Diseases) integrates different European academic groups and small
      enterprises to develop a multidisciplinary training program for talented young
      researchers, to prepare them for leading roles in chronic liver disease research.
      Dr Fabregat has published around 130 articles in indexed journals, as well as
      several book chapters, with her work published in Hepatology, Journal of
      Hepatology, Genes & Development, Cancer Research, Oncogene, FASEB Journal, Free
      Radical in Biology & Medicine, Journal of Cell Science, Journal of Biological
      Chemistry, among others. She is an editorial member of the World Journal of
      Gastroenterology, World Journal of Hepatology, Frontiers in Physiology
      Gastrointestinal Sciences, Frontiers in Pharmacology, Current Signal Transduction
      Therapy and Hepatic Oncology.

PMID- 30191051
TI  - The TGF-beta pathway: a pharmacological target in hepatocellular carcinoma?

PMID- 30191052
TI  - Circulating endothelial cells and risk of progression in patients with
      hepatocellular cancer receiving sorafenib.
AB  - Aim: We investigated the behavior of circulating endothelial cells (CEC) in
      patients with hepatocellular carcinoma (HCC) receiving sorafenib, and whether CEC
      levels were associated with time to progression (TTP). Materials & methods: CECs
      in advanced HCC patients receiving sorafenib were counted at baseline and every 4
      weeks. Results: Twenty four HCC patients were enrolled in the study. Median TTP
      was 3.2 months (1-6). Median baseline CEC levels were 67 cells/ml, with an
      increase of 169.8% after 4 weeks of treatment. Any time CEC levels in patients
      with a TTP lower than 4 months were higher, but not statistically significant,
      compared with those in patients with TTP more than 4 months. Conclusion:
      Treatment with sorafenib changed CEC levels in HCC patients.

PMID- 30191046
TI  - Dysregulated fatty acid metabolism in hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is one of the most frequent and deadly
      malignancies worldwide. Studies are urgently needed on its molecular pathogenesis
      and biological characteristics. Dysregulation of fatty acid (FA) metabolism, in
      which aberrant activation of oncogenic signaling pathways alters the expression
      and activity of lipid-metabolizing enzymes, is an emerging hallmark of cancer
      cells, and it may be involved in HCC development and progression. The current
      review summarizes what is known about dysregulated FA metabolism in HCC and
      pathways through which this dysregulation may regulate HCC survival and growth.
      Our understanding of dysregulated FA metabolism and associated signaling pathways
      may contribute to the development of novel and efficient antitumor approaches for
      patients with HCC.

PMID- 30191050
TI  - When to consider liver transplantation in hepatocellular carcinoma patients?
AB  - Orthotopic liver transplantation (LT) has been regarded as the best cure among
      the three curative treatment modalities. However, when to consider LT in
      hepatocellular carcinoma (HCC) patients remains a complicated clinical question.
      In this article, we will look into the recent updates in the context of LT for
      HCC, including the timing of orthotopic LT (primary or salvage LT), patient
      selection criteria, newer prognostic markers and scoring systems, down-staging
      and bridging therapy, salvage LT and treatment option of post-LT HCC recurrence.
      Evolution of immunosuppressive therapy and future development of the LT for HCC
      will also be discussed.

PMID- 30191053
TI  - Hepatic intra-arterial and systemic chemotherapy followed by maintenance therapy
      for the treatment of cholangiocarcinoma.
AB  - Aim: The aim is to report clinical outcomes of hepatic intra-arterial (IACHT) and
      systemic chemotherapy (SCHT), followed by gemcitabine-based maintenance therapy
      (maintenance), for the treatment of relapsed or unresectable cholangiocarcinoma.
      Patients & methods: In this retrospective observational study, 145
      cholangiocarcinoma patients were treated with Epirubicin-Cisplatin as IACHT
      associated with Capecitabine or 5-fluorouracil as SCHT. Maintenance was performed
      with gemcitabine-based schedule. Toxicity was assessed with NCI-CTCAE and tumor
      response with RECIST 1.1. Results: Tumor response was complete in 1%, partial in
      20%, stable disease in 48% and progression in 31% of patients (3 months after
      therapy). The most frequent adverse events were: anemia (24%), nausea and
      vomiting (33%), alopecia (60%). Conclusion: Cholangiocarcinoma patients may
      benefit from IAHCT-SCHT. Maintenance may prolong clinical benefits.
      ClinicalTrials.gov registry Identifier: NCT01920503.

PMID- 30191054
TI  - Prognostic signatures from hepatocellular carcinoma biopsy.

PMID- 30191055
TI  - 'Hug sign': a new radiological sign of intraprocedural success after combined
      treatment for hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is one of the most common cancers in the world. A
      careful multidisciplinary assessment of tumor characteristics, liver function and
      physical status is required for proper therapeutic management. In recent years,
      several studies have supported the feasibility and benefit of combined therapy in
      the treatment of single large HCC, defined as those exceeding 3 cm in size. We
      present a case of combined treatment using radiofrequency ablation followed by
      trans-arterial chemoembolization with radiopaque embolic beads. The aim of this
      technical report was to describe the radiologic findings during combined
      radiofrequency ablation and radiopaque bead embolization, pointing out the
      differences and the potential advantages of using radiopaque beads compared with
      non-radiopaque beads. Furthermore, it is also the first report on using
      radiopaque beads in combined treatment for HCC.

PMID- 30191056
TI  - Chemoembolization versus radioembolization for the treatment of unresectable
      intrahepatic cholangiocarcinoma in a single institution image-based efficacy and
      comparative toxicity.
AB  - Aim: Compare radioembolization (Y90) and chemoembolization (CE) for the treatment
      of unresectable intrahepatic cholangiocarcinoma (UICC). Materials & methods:
      Institutional Review Board-approved, retrospective search was performed. Forty
      patients with UICC were treated with either Y90 (n = 25, 39 treatments) or CE (n
      = 15, 35 treatments). Comparative analysis was performed using Student's t and
      fisher-exact tests. Multivariable-logistic regression was also performed.
      Results: Median ages were 60 and 64 years for CE and Y90 groups, respectively (p
      = 0.798). Patient variables including age, Eastern Cooperative Oncology Group
      score, tumor burden, extra-hepatic disease, prior chemotherapy and prior surgery
      were similar between groups. Adverse events were similar in both groups (CE 20%,
      Y90 26%; p > 0.9). Overall response rate (CE 6%, Y90 4%; p > 0.9) and disease
      control rate (CE 46%, Y90 48%; p > 0.9) were statistically similar. Multilogistic
      regression did not identify any variables that correlated with disease control
      rate, including Eastern Cooperative Oncology Group score and tumor burden.
      Conclusion: Our observation shows that CE and Y90 display similar toxicity and
      disease control in the treatment of UICC.

PMID- 30191057
TI  - Nonalcoholic fatty liver disease and hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) in patients with nonalcoholic fatty liver disease
      is becoming more common globally. The incidence of HCC due to nonalcoholic
      steatohepatitis in comparison to other etiologies is increasing. This is due to
      the pandemic of obesity and diabetes mellitus, two important risk factors for
      HCC. HCC arising in this context occurs in about 40% of the cases in a liver
      which is not yet cirrhotic. This has implications regarding the population which
      should be enrolled in an HCC surveillance program and regarding the treatment
      options. Surgery is more frequently contemplated in patients with HCC and no
      cirrhosis. However, patients with nonalcoholic steatohepatitis-induced HCC have
      frequent co-morbidities which have to be taken into account when developing a
      management strategy. Interestingly, these patients are frequently on medications
      which have been suggested to decrease the risk to develop HCC.

PMID- 30191058
TI  - Biomarker development for hepatocellular carcinoma early detection: current and
      future perspectives.
AB  - Early detection of hepatocellular carcinoma (HCC) leads to improved survival;
      however, current early detection strategies for HCC surveillance are ineffective.
      Thus, there has been interest in developing biomarkers to aid in the early
      detection HCC. In this review, we discuss the five phases of biomarker discovery
      that are necessary for clinical implementation. We also describe the most
      promising investigational biomarkers and their phase of discovery. We review
      several promising technologies for the early detection of HCC, including miRNA,
      metabolomics and proteomics. Promisingly, there are samples from multiple
      longitudinal cohorts of patients with cirrhosis in the USA that are being
      collected in order to validate candidate biomarkers for HCC. A biomarker-based
      strategy has the potential to become the primary surveillance method for HCC
      detection.

PMID- 30191059
TI  - Radiologic criteria of response to systemic treatments for hepatocellular
      carcinoma.
AB  - Sorafenib has been the only approved systemic therapy for hepatocellular
      carcinoma until very recently. However, the radiologic assessment of its
      biological activity is a disputed matter as at least five different criteria have
      been proposed. In this review, we describe the characteristic of the Response
      Evaluation Criteria In Solid Tumors (RECIST), European Association for the Study
      of The Liver (EASL), modified RECIST (mRECIST), Response Evaluation Criteria In
      the Cancer of the Liver (RECICL) and Choi criteria. The existing comparative
      studies are reported together with recent pieces of evidence, analyzing the
      reasons behind the split between recommendations of the scientific societies and
      regulatory agencies. Future perspectives in the wake of the impending results of
      the immunotherapy trials are also discussed.

PMID- 30191060
TI  - Neuronal pentraxin receptor-1 is a new cerebrospinal fluid biomarker of
      Alzheimer's disease progression.
AB  - Background: Alzheimer's disease (AD) is the most common type of dementia, with
      progressive onset of clinical symptoms. The main pathological hallmarks are brain
      deposits of extracellular amyloid beta plaques and intracellular neurofibrillary
      tangles (NFT). Cerebrospinal fluid reflects pathological changes in the brain;
      amyloid beta 1-42 is a marker of amyloid plaques, while total and phosphorylated
      tau are markers of NFT formation. Additional biomarkers associated with disease
      pathogenesis are needed, for better prognosis, more specific diagnosis,
      prediction of disease severity and progression and for improved patient
      classification in clinical trials. The aim of the present study was to evaluate
      brain-specific proteins as potential biomarkers of progression of AD. Methods:
      Overall, 30 candidate proteins were quantified in cerebrospinal fluid (CSF)
      samples from patients with mild cognitive impairment (MCI) and mild, moderate and
      severe AD dementia (n=101) using mass spectrometry-based selected reaction
      monitoring assays. ELISA was used for neuronal pentraxin receptor-1 (NPTXR)
      confirmation. Results: The best discrimination between MCI and more advanced AD
      stages (moderate and severe dementia) was observed for protein NPTXR (area under
      the curve, AUC=0.799). A statistically different abundance of this protein was
      observed between the two groups, with severe AD patients having progressively
      lower levels (p<0.05). ELISA confirmed lower levels in AD, in a separate cohort
      that included controls, MCI and AD patients. Conclusions: We conclude that NPTXR
      protein in CSF is a novel potential biomarker of AD progression and could have
      important utility in assessing treatment success in clinical trials.

PMID- 30191061
TI  - Establishing the need for clinical follow-up after emergency appendicectomy in
      the modern era: Retrospective case series of 145 patients.
AB  - Introduction: Emergency appendicectomy (EA) is a commonly performed operation,
      with an increasing number of EAs being performed as day-case. The aim of this
      study is to establish if there is a need for post-operative follow-up and if this
      could prevent adverse outcomes. Methods: A retrospective analysis of patients who
      underwent EA at multiple centres over a six-month period was undertaken. They
      were contacted by telephone and a standardised questionnaire was used to
      ascertain post-operative outcomes, including duration of analgesia use, duration
      before return to normal daily activity (ADLs), surgical site infection rates
      (SSI) and rates of re-presentation to medical services. Patients were stratified
      into those who underwent laparoscopic versus open appendicectomy, smokers versus
      non-smokers, and body mass index (BMI). Results: A total of 145 patients were
      included in the study. Patients undergoing open surgery (vs. laparoscopic
      surgery) required analgesia for significantly longer periods, with a
      significantly longer return to ADLs. Smokers, when compared to non-smokers
      experienced a significantly longer return to work/school; and significantly
      higher risk of SSI and re-presenting to accident & emergency; as did patients
      with a BMI >30 when compared to those with a BMI <30. Conclusion: Most patients
      do not need formal outpatient assessment after EA. However, there is clearly a
      subset of higher risk patients who may benefit from this - patients who are
      smokers or obese. They have prolonged recovery times, and are at greater risk of
      SSI. Earlier surgical outpatient follow-up of these patients could prevent
      adverse outcomes.

PMID- 30191062
TI  - Oncological outcomes of abdominoperineal resection for the treatment of low
      rectal cancer: A retrospective review of a single UK tertiary centre experience.
AB  - Background: The use of abdominoperineal resection (APR) in the management of low
      rectal cancer has received criticism over high rates of incomplete resection due
      to tumour involvement at the circumferential resection margin. Extralevator
      abdominoperineal resection has been advocated as a means of improving complete
      resection. However, Extralevator abdominoperineal resection can result in
      increased cost, morbidity and reduced quality of life.This study aims to assess
      the histological features and long-term outcomes of patients undergoing standard
      abdominoperineal resection and discusses the potential role of Extralevator
      abdominoperineal resection in this cohort. Method: A retrospective review of a
      prospectively maintained database of rectal cancer patients at a single centre.
      Patients undergoing standard APR were included from 01/06/2007 to 31/05/2012 to
      allow a minimum 2-year follow-up. Data was collected on age, gender, co
      morbidity, pre-operative stage, neo-adjuvant therapy, histology, recurrence and
      mortality. Results: Seventy patients were identified (45 (64%) male, median age
      67; (range 36-85)). 12 (17.1%) patients had a positive circumferential resection
      margin; 4 (6.1%) tumours were located anteriorly, 8 (11%) were located
      posteriorly or laterally and may potentially have been completely resected with
      extralevator abdomino-perineal resection, Number-needed to treat = 9. Positive
      circumferential resection margin was more common in advanced tumours (p < 0.001).
      Local recurrence was more common with positive circumferential resection margins
      (16.7% Vs 0%, p = 0.027), with no statistically significant difference in 5-year
      survival, although there was a tendency towards worse survival in these patients.
      Conclusion: Positive circumferential resection margin following APR resulted in
      significantly increased local recurrence with a trend towards poorer survival
      outcomes. Extralevator abdomino-perineal resection may have benefited some of
      these patients with locally advanced tumours and postero-lateral recurrences.
      However, this has to be balanced against exposing patients to increased risk of
      adverse events. We would recommend selective use of Extralevator abdominoperineal
      resection for locally advanced and node-positive tumours although further studies
      to help refine selection criteria are required with long-term follow-up.

PMID- 30191064
TI  - Editorial.

PMID- 30191063
TI  - Genetic diversity at the C-terminal domain of knob-associated histidine-rich
      protein (KAHRP) of Plasmodium falciparum isolates from Burundi, Eastern Africa.
AB  - The knob-associated histidine-rich protein (KAHRP) is an exported parasite
      protein and the major component of infected erythrocytes by Plasmodium
      falciparum. P. falciparum histidine-rich protein-1 (PfHRP-1) is docked by KAHRP,
      which this interaction plays a significant role in cytoadherence of the malaria
      protozoan to erythrocytes and pathogenicity. The most polymorphic region of the
      PfHRP-1 is the C-terminal of decapeptide repeat domain (region III). The main
      objective of this study was to explore the genetic diversity at the region III of
      KAHRP in P. falciparum isolates from Burundi. In the present study, the nested
      PCR was performed for the amplification of the coding gene (kahrp gene) for
      region III in 35 P. falciparum isolates from Burundi. The nested PCR products of
      seven randomly selected isolates were purified and then sequenced. As the result,
      three allelic forms (340 bp, 370 bp, and 400 bp) were seen at the C-terminal
      domain of kahrp gene. The existence of multiple alleles of the kahrp gene
      revealed the presence of different P. falciparum strains in Burundi. It is
      suggested that the results could be useful in designing and the improvement of
      targeted therapy agents for falciparum malaria.

PMID- 30191065
TI  - A clash at the petri dish: transferring embryos with known genetic anomalies.
AB  - Advancing technologies in genetic testing of preimplantation embryos enable IVF
      patients to access detailed information about their future child's health status,
      facilitating and complicating their reproductive decision-making. Testing for
      embryonic genetic anomalies linked to future health has grown increasingly
      sophisticated. A patient's decision to seek transfer of a health-affected embryo
      may or may not be compatible with her physician's professional conscience,
      potentially resulting in a clash at the petri dish. This article sets out
      arguments in support of physician decisions to assist or decline to assist in the
      transfer of anomalous embryos upon patient request. Arguments in support of
      transfer include the preeminence of a patient's reproductive liberty, the value
      of equal protection as applied to pre- and post-implantation embryos, the
      allocation of dispositional authority over embryos, and the frailties of
      predicting a child's future health experience. Arguments that bolster a
      provider's decision to decline requests for transfer include the role of
      physician autonomy in the doctor-patient relationship, the theories of
      reproductive non-maleficence and procreative beneficence, and legitimate concerns
      over future legal liability. Regardless of a clinic's ultimate position, this
      article advocates that providers create or adopt detailed policies setting forth
      their preferences and practices regarding anomalous embryo transfer.

PMID- 30191066
TI  - The tyranny of choice: reproductive selection in the future.
AB  - This article explores the enormous challenges to reproductive decision making
      that could result from two emerging technologies: the potential capacity to
      create vast numbers of embryos for preimplantation genetic diagnosis and the
      ability to obtain ever more predictive information about the embryo. Together
      these technologies could change our reproductive experience, exacerbate existing
      inequities, and profoundly affect reproductive decision making. Simply
      comprehending the dizzying amounts of predictive information about the health and
      traits of future children will overwhelm future parents. But trying to choose
      embryos with the 'best' combination of genetic variants could be paralyzing.
      Nevertheless, numerous pressures will make this technology alluring, compelling
      providers to develop remedies to assist future parents with these difficult
      reproductive decisions. The remedies, however, will create their own challenges.
      Some might test the limits of reproductive autonomy and heighten social
      inequities. A particularly vexing remedy would be the development of algorithms
      for embryo selection, which could routinize reproductive decisions, reduce
      societal diversity, exacerbate 'choice overload' effects, challenge professional
      norms, and raise the specter of eugenics. Ultimately, this article is a
      cautionary tale urging circumspection as technological advancements seem to
      propel us inevitably toward a reproductive future that could create a tyranny of
      choice.

PMID- 30191067
TI  - Uterus transplantation in and beyond cisgender women: revisiting procreative
      liberty in light of emerging reproductive technologies.
AB  - Whilst internationally a growing body of literature is emerging on uterus
      transplantation as the latest advance in assisted reproductive technology, much
      of this has been devoted to responding to the ethical questions raised by this
      procedure in the context of its immediate purpose, to restore fertility in
      cisgender women. Very few have addressed whether it can be claimed that there is
      a right to gestate under the umbrella of procreative liberty, nor whether such a
      right, if it does exist, applies not only to cisgender women, but also
      transgender and gender variant individuals and cisgender men. In honour of
      Professor Robertson, I advance the debate further by examining the arguments put
      forward in his last paper and whether the right to gestate extends beyond
      cisgender women.

PMID- 30191068
TI  - Creating life after death: should posthumous reproduction be legally permissible
      without the deceased's prior consent?
AB  - Scientific advances enable to retrieve and use gametes of a deceased person,
      thereby creating a child after the death of a genetic parent. This article
      reviews and compares legislation governing posthumous reproduction in the United
      States, the United Kingdom, Australia, and Israel. It shows that each country has
      its own distinctive features, yet three common elements exist-legal ambiguity, a
      requirement for prior consent, and permission for the partner, but not the
      parents, to retrieve and use the deceased's gametes. The article demonstrates
      that courts often do not follow the legal requirements, and thus there are no
      clear guiding principles regarding posthumous reproduction. The article then
      discusses three justifications for permitting posthumous reproduction in the
      absence of the deceased's prior consent. The first justification relates to an
      interest in 'genetic continuity', which reflects people's desire in leaving a
      'piece' of themselves in the world and maintaining a chain of continuity. The
      second justification concerns the 'respect-for-wishes' model of autonomy,
      according to which people must be treated in a way that we assume they would want
      to be treated. The third justification touches upon the interests of the
      deceased's partner and parents, as well as of the resulting child.

PMID- 30191069
TI  - Privatizing procreative liberty in the shadow of eugenics.
AB  - The late John Robertson is renowned for the theory of 'procreative liberty' that
      he expounded in his pioneering book, Children of Choice. Procreative liberty
      captures the 'freedom to reproduce without sex' above and beyond the 'freedom to
      have sex without reproduction' that are recognized by constitutional rights to
      abortion and birth control. Most controversial among Robertson's work on
      procreative liberty was its application to prenatal selection. Unless the state
      had very good reasons, he argued, people should be free to access reproductive
      medicine or technology to have a child who or would be born with particular
      traits. Prospective parents in the USA today face no official limits in using
      sperm banks, egg vendors, IVF clinics, or surrogacy agencies with an eye toward
      choosing for certain characteristics. But should they be protected, this essay
      asks, when mix-ups or misdiagnoses thwart the selection of offspring traits? The
      best answer to this question extends the theory of procreative liberty from
      government restrictions to professional negligence. It also demands sensitivity
      to genetic uncertainty, the limits of private law, and the history of eugenics in
      America. Or so I argue in this tribute to the inimitable John Robertson.

PMID- 30191070
TI  - Surrogacy, privacy, and the American Convention on Human Rights.
AB  - Under the Inter-American Human Rights System, individuals have a right to access
      reproductive technologies. However, the legal status of surrogacy agreements in
      State Parties to the American Convention on Human Rights (ACHR) is mostly
      uncertain. The article discusses whether a complete ban on surrogacy is
      compatible with the ACHR. It considers potential objections to surrogacy
      agreements: 'corruption objections'-surrogacy denigrates the nature of what is
      being exchanged-, the potential exploitation of surrogates and welfare concerns
      of children born from surrogacy. The article concludes that States Parties to the
      ACHR should allow both altruistic and commercial surrogacy, but that regulatory
      schemes for appropriate protection of the rights of surrogates, intending
      parents, and children resulting from surrogacy ought to be secured.

PMID- 30191071
TI  - State incentives to promote organ donation: honoring the principles of
      reciprocity and solidarity inherent in the gift relationship.
AB  - Organ transplantation saves the lives of thousands of patients worldwide every
      year. However, a chronic organ shortage overshadows this success. We define the
      organ shortage as a public health problem due to its serious consequences on
      patients and society. This definition raises the question of the state's role in
      transplantation medicine. It leads us to formulate a public policy promoting
      organ donation through state incentives, ie regulatory instruments to reward
      individuals' willingness to donate. Incentives allow the state to express
      gratitude for the solidary act of the donor toward the recipient and society. In
      an original approach, we integrate sociological findings as to the act of
      donation-the concept of reciprocity most importantly-into the core attributes of
      such a public policy. Addressing regulatory design questions, we present
      incentives such as allocation priority, tax benefits, health insurance discounts,
      and coverage of funeral costs. We also examine the unique non-financial incentive
      successfully implemented in Israel. We then discuss the legal and ethical
      framework in which state incentives have to operate, concluding that normative
      constraints can be addressed through law reform. Finally, we focus on aspects
      neglected so far in public information campaigns and discuss the interaction
      between state policy and public opinion.

PMID- 30191072
TI  - Suicide and Death with Dignity.

PMID- 30191073
TI  - 'NEUROPHOBIA', a Reply to Patterson.

PMID- 30191074
TI  - Describing the leadership capabilities of advanced practice nurses using a
      qualitative descriptive study.
AB  - Aim: The aim of this study is to explore advanced practice nurses' perceptions of
      their leadership capabilities. Design: A qualitative descriptive methodology
      informed by a well-established leadership framework was used to explore advanced
      practice nurses' perceptions of their leadership. Methods: Purposive sampling of
      advanced practice nurses working in tertiary acute care facilities in Eastern
      Canada was employed. Data sources included face-to-face interviews and document
      analysis. Fourteen advanced practice nurses participated in two audio-taped semi
      structured interviews from March 2013-January 2014. Data were transcribed and
      analysed using NVIVO 10 software and content analysis. Results: Two main themes
      were identified: "Patient-focused leadership" and "organization and system
      focused leadership". These two themes are further described through leadership
      domains and capabilities that clearly articulate advanced practice nursing
      leadership and its contribution to improving the care environment for patients
      and families, nurses and other healthcare providers, organizations and the
      healthcare system.

PMID- 30191076
TI  - Magnesium Protects in Episodes of Critical Perfusion after Aneurysmal SAH.
AB  - Background: To analyze whether magnesium has a neuroprotective effect during
      episodes that indicate a critical brain perfusion after aneurysmal subarachnoid
      hemorrhage (SAH). Methods: 107 patients with aSAH were randomized to continuously
      receive intravenous magnesium sulfate with target serum levels of 2.0 - 2.5
      mmol/l (n = 54) or isotonic saline (n = 53). Neurological examination and
      transcranial Doppler sonography (TCD) were performed daily, Perfusion-CT (PCT)
      was acquired in 3-day intervals, angiography in case of suspected vasospasm. The
      primary endpoint was the development of secondary infarction following episodes
      of delayed ischemic neurological deficit (DIND), elevated mean flow velocity
      (MFV) in TCD or pathological findings in PCT. Results: In the magnesium group, 9
      episodes of DIND were registered, none was followed by secondary infarction. In
      the control group, 23 episodes of DIND were registered, 9 were followed by
      secondary infarction (p < 0.05). In the magnesium group, 114 TCD-measurements
      showed an elevated MFV(> 140 cm/s). 7 were followed by new infarction. In control
      patients, 135 measurements showed elevated MFV, 32 were followed by new
      infarction (p < 0.05). 10 of 117 abnormal PCT-findings were followed by new
      infarction, compared to 30 of 122 in the control-group (p < 0.05). Conclusion:
      DIND, elevated MFV in TCD and abnormal PCT are findings which are associated with
      an increased risk to develop delayed secondary infarction. The results of this
      analysis suggest that magnesium-treatment may reduce the risk to develop
      infarction in a state of critical brain perfusion.

PMID- 30191075
TI  - Exercise for stroke prevention.
AB  - We review evidence concerning exercise for stroke prevention. Plausible
      biological reasons suggest that exercise would be important in preventing stroke.
      While definitive randomised controlled trials evaluating the impact of physical
      activity (PA) and exercise on preventing stroke and mortality are lacking,
      observational studies, small randomised controlled trials and meta-analyses have
      provided evidence that PA and exercise favourably modify stroke risk factors,
      including hypertension, dyslipidaemia, diabetes, sedentary lifestyle, obesity,
      excessive alcohol consumption and tobacco use. It is, therefore, important to
      understand the factors associated with poststroke PA/exercise and
      cardiorespiratory fitness. Positively associated factors include self-efficacy,
      social support and quality of patients' relationships with health professionals.
      Negatively associated factors include logistical barriers, medical comorbidities,
      stroke-related deficits, negative exercise beliefs, fear of falling, poststroke
      fatigue, arthropathy/pain and depression. Definitive research is needed to
      specify efficacious behavioural approaches to increase poststroke exercise.
      Effective techniques probably include physician endorsement of exercise
      programmesto patients, enhancement of patient-professional relationships,
      providing patients an exercise rationale, motivational interviewing,
      collaborative goal-setting with patients, addressing logistical concerns, social
      support in programsmes, structured exercise programming, individualised
      behavioural instruction, behavioural diary recording, reviewing behavioural
      consequences of exercise efforts, reinforcing successful exercise performance.
      Exercise programming without counselling may increase short-term activity; simple
      advice or information-giving is probably ineffective. Older patients or those
      with cognitive impairment may need increased structure, with emphasis on
      behaviour per se, versus self-regulation skills. We support the latest American
      Heart Association/American Stroke Association guidelines (2014) recommending PA
      and exercise for stroke prevention, and referral to behaviourally oriented
      programmes to improve PA and exercise.

PMID- 30191077
TI  - Evaluation of Two Types of Drug Treatment with QEEG in Children with ADHD.
AB  - Aims: The aim of this study is to evalute the effects of methylphenidate and
      atomoxetine treatments on electroencephalography (EEG) signals in volunteer
      children diagnosed with Attention Deficit and Hyperactivity Disorder(ADHD).
      Methods: The study contained 40 children all of whom were between the ages of 7
      and 17. The participants were classified into two groups as ADHD (n=20), which
      was in itself divided into two groups as ADHD-MPH (ADHD- Metylphenidate
      treatment) (n=10) and as ADHD-ATX (ADHD-Atomoxetin treatment) (n=10), and one
      control group (n=20). Following the first EEG recordings of the ADHD group, long
      acting methylphenidate dose was applied to one ADHD group and atomoxetine dose
      was applied to the other ADHD group. The effect of optimal dosage is about for 4
      6 weeks in general. Therefore, the response or lack of response to the treatment
      was evaluated three months after the beginning of the treatment.After
      methylphenidate and atomoxetine drug treatment, in order to obtain mean and
      maximum power values for delta, theta, alpha and beta band, the EEG data were
      analyzed. Results: The EEG power spectrum densities in all the bands yielded
      similar findings in both methylphenidate and atomoxetine. Although statistically
      significant frequency values of the electrodes were amplitude and maximally
      varied, in general, they appeared mostly at both frontal and temporal regions for
      methylphenidate and atomoxetine. Conclusion: Especially, after atomoxetine
      treatment, Quantitative Electroencephalography (QEEG) rates at frontal area
      electrodes were found statistically more significant than methylphenidate QEEG
      rates. What has been researched in this study is not only whether QEEG is likely
      to support the diagnosis, but whether changes on QEEG by treatment may be related
      to the severity of ADHD as well.

PMID- 30191079
TI  - Generalized Score Functions for Causal Discovery.
AB  - Discovery of causal relationships from observational data is a fundamental
      problem. Roughly speaking, there are two types of methods for causal discovery,
      constraint-based ones and score-based ones. Score-based methods avoid the
      multiple testing problem and enjoy certain advantages compared to constraint
      based ones. However, most of them need strong assumptions on the functional forms
      of causal mechanisms, as well as on data distributions, which limit their
      applicability. In practice the precise information of the underlying model class
      is usually unknown. If the above assumptions are violated, both spurious and
      missing edges may result. In this paper, we introduce generalized score functions
      for causal discovery based on the characterization of general (conditional)
      independence relationships between random variables, without assuming particular
      model classes. In particular, we exploit regression in RKHS to capture the
      dependence in a non-parametric way. The resulting causal discovery approach
      produces asymptotically correct results in rather general cases, which may have
      nonlinear causal mechanisms, a wide class of data distributions, mixed continuous
      and discrete data, and multidimensional variables. Experimental results on both
      synthetic and real-world data demonstrate the efficacy of our proposed approach.

PMID- 30191080
TI  - Attachment, Bushfire Preparedness, Planning, and Response among Animal Guardians:
      A South Australian Case Study.
AB  - BACKGROUND: Animal ownership has been identified as a risk factor for human
      survivability of natural disasters. Animal guardians have been reported to react
      or act in ways that may put their own safety and that of emergency services
      personnel at risk when faced with a natural disaster. Recent research has
      suggested that this risk factor could be reconfigured as a protective factor,
      whereby desires to save animals from natural disaster harm could motivate
      increased planning and preparedness behaviours amongst animal guardians. However,
      there has been no research to determine if bushfire planning and response
      behaviours differ between pet owners with low and high attachment; and how the
      relationship may differ in relation to small or large animals. METHODS AND
      PROCEDURE: We investigated the relationship between people's emotional attachment
      to different types of pets and their preparation and actions during the Pinery
      bushfire in South Australia in November 2015. Thirty-four people who were
      impacted by the fire participated in an online survey. Data were collected about
      their preparedness, planning and response behaviours as well as their animal
      attachment (high or low). RESULTS: We identified 10 characteristics (behaviours,
      attributes, skills and beliefs) associated with high animal attachment scores,
      and eight associated with low animal attachment scores. DISCUSSION: Our
      discussion of the differences in demographics, preparedness, planning and
      response characteristics of participants with high and low animal attachment
      confirms research suggesting that animal guardians take risks to save their
      animals during disasters. Our findings also support recent propositions that
      animal attachment and ownership could be used to increase the natural disaster
      preparedness and survivability of animal guardians. However, making sure that
      animal attachment functions as a protective factor requires active and effective
      intervention through education, behaviour change and social marketing strategies.
      Whilst our study is high in ecological validity, future research with larger
      samples sizes is required to determine the generalisability of our findings to
      animal owners and guardians in other locations, facing fires with other
      characteristics, especially for owners and guardians with low levels of
      attachment.

PMID- 30191078
TI  - Colorectal cancer screening use among insured adults: Is out-of-pocket cost a
      barrier to routine screening?
AB  - AIM: To describe the characteristics of adults who needed to see a doctor in the
      past year but could not due to the extra cost and assess the impact of limited
      financial resources on the receipt of routine fecal occult blood test,
      sigmoidoscopy, or colonoscopy for colon cancer screening among insured patients.
      METHODS: Data obtained from the 2012 Behavioral Risk Factor Surveillance System
      included 215436 insured adults age 50-75 years. We computed frequencies, adjusted
      odds ratios (aORs), and 95%CIs using SAS v9.3 software. RESULTS: Nine percent of
      the study population needed to see a doctor in the past year but could not
      because of cost. The numbers were significantly higher among those aged 50-64 (P
      < 0.0001), Non-Hispanic Whites (P < 0.0001), and those with a primary care
      physician (P < 0.0001) among other factors. Adjusting for possible confounders,
      aORs for not seeing the doctor in the past year because of cost were: stool
      occult blood test within last year aOR = 0.88; 95%CI: 0.76-1.02, sigmoidoscopy
      within last year aOR = 0.72; 95%CI: 0.48-1.07, colonoscopy within the last year
      aOR = 0.91; 95%CI: 0.81-1.02. CONCLUSION: We found that the limited financial
      resources within the past 12 mo were significantly associated with colorectal
      cancer (CRC) non-screening. Patients with risk factors identified in this study
      should adhere to CRC guidelines and should receive financial help if needed.

PMID- 30191081
TI  - Community Perspective on Policy Options for Resettlement Management: A Case Study
      of Risk Reduction in Bududa, Eastern Uganda.
AB  - INTRODUCTION: Despite existing policy actions on Disaster Risk Reduction (DRR),
      many community members in Bududa still continue to settle in high-risk areas re
      zoned for nonsettlement. There seems to be an apparent information asymmetry on
      expectations between the community and Government. The challenge then is 'how to
      consult communities and seek their opinion in an adequately representative
      unbiased way'. This paper sets out to explore policy options on resettlement
      management as a DRR approach and how engaging with communities in a public
      discourse using the Deliberative Polling (DP) approach; to obtain their opinions
      and insights on these policy issues, revealed underlying challenges to policy
      implementation. METHODS: A qualitative study was conducted in Bududa in eastern
      Uganda with fourteen group discussions; comprising 12-15 randomly assigned
      participants of mixed socio-economic variables. Trained research assistants and
      moderators collected data. All discussions were audio taped, transcribed verbatim
      before analysis. Data were analyzed using latent content analysis by identifying
      codes from which sub-themes were generated and grouped into main themes on policy
      options for resettlement management. RESULTS AND DISCUSSION: We used Deliberative
      Polling, an innovative approach to public policy consultation and found that
      although the community is in agreement with most government policy options under
      resettlement management, they lacked an understanding of the rationale underlying
      these policy options leading to challenges in implementation. The community
      members seemed uncertain and had mistrust in government's ability to implement
      the policies especially on issues of compensation for land lost. Key Words:
      Policy, Deliberative Polling, Climate change, risk-reduction, landslides, Uganda.

PMID- 30191082
TI  - Clinical Characteristics of Functional Movement Disorders: A Clinic-based Study.
AB  - Background: Functional movement disorders are recognized as a "crisis" in
      neurology. We aimed to determine the rate of incidence of functional movement
      disorder patients at a university outpatient neurology clinic in South Korea, and
      highlight the clinical and phenomenological characteristics. Methods: Patients
      who were assessed by a movement disorders neurologist at a university hospital
      between March 2016 and May 2017 were screened for functional movement disorders.
      Demographic and clinical data were reviewed, and the phenomenology of movements
      was studied. Results: Of 321 patients evaluated for the chief complaint of a
      movement abnormality, approximately 10% (31 patients) were diagnosed with a
      functional movement disorder. The female to male ratio was 7:1 (27 females to
      four males). The mean age at presentation was 53 years (standard error 3.6
      years), and the mean disease duration was 5 years (standard error 1.4 years).
      Sixty-one percent (19 out of 31 patients) had a past medical history of
      depression, anxiety, or other psychiatric illnesses. Tremor and speech
      abnormalities were most prevalent (19 and 12 patients, respectively). Onset was
      reported to be abrupt in 14 patients (45%). Thirteen (42%) patients were found to
      have improvement at a follow-up visit, 10 (32%) had no improvement, and eight
      (26%) were lost to follow-up. Discussion: Functional movement disorders are not
      uncommon in the outpatient neurology clinic. Our results confirm that tremor is
      the most frequent movement occurring in functional movement disorders, and the
      most commonly affected body parts were found to be the upper and lower
      extremities. Speech was also found to be frequently involved (39%). Patients with
      no improvement at follow-up had longer mean disease duration (6.2 years),
      consistent with previous observations that prolonged symptom duration is
      associated with poor clinical outcome. Our study results obtained from a Korean
      population suggest that previous observations on functional movement disorders
      from other regions hold true in Eastern Asia.

PMID- 30191083
TI  - Suppression of Harmaline Tremor by Activation of an Extrasynaptic GABAA Receptor:
      Implications for Essential Tremor.
AB  - Background: Metabolic imaging has revealed excessive cerebellar activity in
      essential tremor patients. Golgi cells control cerebellar activity by releasing
      gamma-aminobutyric acid (GABA) onto synaptic and extrasynaptic receptors on
      cerebellar granule cells. We postulated that the extrasynaptic GABAA receptor
      specific agonist THIP (gaboxadol; 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol)
      would suppress tremor in the harmaline model of essential tremor and, since
      cerebellar extrasynaptic receptors contain alpha6 and delta subunits, would fail
      to do so in mice lacking either subunit. Methods: Digitally measured motion
      power, expressed as 10-16 Hz power (the tremor bandwidth) divided by background 8
      32 Hz motion power, was accessed during pre-harmaline baseline, pre-THIP
      harmaline exposure, and after THIP administration (0, 2, or 3 mg/kg). These low
      doses were chosen as they did not impair performance on the straight wire test, a
      sensitive test for psychomotor impairment. Littermate delta wild-type and
      knockout (Gabrd+/+, Gabrd-/-) and littermate alpha6 wild-type and knockout
      (Gabra6+/+, Gabra6-/- ) mice were tested. Results: Gabrd+/+ mice displayed tremor
      reduction at 3 mg/kg THIP but not 2 mg/kg, and Gabra6+/+ mice showed tremor
      reduction at 2 and 3 mg/kg. Their respective subunit knockout littermates
      displayed no tremor reduction compared with vehicle controls at either dose.
      Discussion: The loss of anti-tremor efficacy with deletion of either delta or
      alpha6 GABAA receptor subunits indicates that extrasynaptic receptors containing
      both subunits, most likely located on cerebellar granule cells where they are
      highly expressed, mediate tremor suppression by THIP. A medication designed to
      activate only these receptors may display a favorable profile for treating
      essential tremor.

PMID- 30191084
TI  - Holmes Tremor Partially Responsive to Topiramate: A Case Report.
AB  - Background: Holmes tremor is a rare symptomatic movement disorder, characterized
      by a combination of resting, postural, and intention tremor. It is usually caused
      by lesions in the brainstem, thalamus, and cerebellum. Despite pharmacological
      advances, its treatment remains a challenge; many medications have been used with
      various degrees of effectiveness. Stereotactic thalamotomy and deep brain
      stimulation in the ventralis intermedius nucleus have been effective surgical
      procedures in cases refractory to medical treatment. Case Report: Here we report
      a young woman with topiramate-responsive Holmes tremor secondary to a brainstem
      cavernoma. Discussion: Herein we report a Holmes tremor responsive to Topiramate.

PMID- 30191085
TI  - Orthostatic Tremor is Responsive to Bilateral Thalamic Deep Brain Stimulation:
      Report of Two Cases Performed Asleep.
AB  - Background: Orthostatic tremor (OT) is a hyperkinetic movement disorder
      characterized by rapid tremor in the lower extremities or trunk upon standing.
      Case Report: We report two patients presenting with OT, whose symptoms improved
      markedly following asleep bilateral thalamic deep brain stimulation (DBS)
      surgery. Discussion: Medically refractory OT can respond favorably to asleep
      bilateral DBS surgery similar to awake surgery, and may have the advantages of
      less psychological trauma to the patient, shorter procedure times, and less
      exposure to anesthesia.

PMID- 30191086
TI  - Diagnosis of Spinocerebellar Ataxia in the West Indies.
AB  - Background: Access to medical care in many regions is limited by socioeconomic
      status, at both the individual and the community level. This report describes the
      diagnostic process of a family residing on an underserved Caribbean island where
      routine neurological care is typically addressed by general practitioners, and
      genetic diagnosis is not available through regular medical channels. The
      diagnosis and management of neurodegenerative disorders is especially challenging
      in this setting. Case Report: We diagnosed a family with spinocerebellar ataxia
      type 3 (SCA3) in an underdeveloped nation with limited access to genetic medicine
      and no full-time neurologist. Discussion: Molecular diagnosis of the SCAs can be
      challenging, even in developed countries. In the Caribbean, genetic testing is
      generally only available at a small number of academic centers. Diagnosis in this
      family was ultimately made by utilizing an international, pro bono, research
      based collaborative process. Although access to appropriate resources, such as
      speech, physical, and occupational therapies, is limited on this island because
      of economic and geographical factors, the provision of a diagnosis appeared to be
      ultimately beneficial for this family. Identification of affected families
      highlights the need for access to genetic diagnosis in all communities, and can
      help direct resources where needed.

PMID- 30191088
TI  - Athetoid Movements as Initial Manifestation of Primary Sjogren Syndrome.
AB  - Background: Primary Sjogren syndrome (pSS) is an autoimmune disorder
      characterized by exocrine gland and extraglandular symptoms. We present a case
      report of pSS with an initial presentation of athetoid movements. Case Report: A
      74-year-old female presented with a 2-month history of slow undulating movements
      in her trunk and thighs that eventually spread to her neck and lower extremities.
      She also reported dry eyes, dry mouth, as well as pain in her shoulders and
      thighs. Her proinflammatory markers and rheumatologic profile were positive. Her
      salivary gland biopsy revealed a Focus score > 2. Brain magnetic resonance
      imaging was normal. A diagnosis of pSS was made. The patient's symptoms improved
      with hydroxychloroquine, pilocarpine, gabapentin, and clonazepam. Discussion:
      Clinicians should consider and screen for primary autoimmune disorders as a cause
      of subacute athetoid movements in elderly patients. Although aggressive treatment
      has been recommended, treatment should be tailored to each patient's specific
      needs.

PMID- 30191090
TI  - Spectrochemical Properties and Solvatochromism of Tetradentate Schiff Base
      Complex with Nickel: Calculations and Experiments.
AB  - Invited for this month's cover picture is Dr. Agnieszka Gonciarz and her team.
      The team's cooperation began recently when they met at the Military University of
      Land Forces (MULF) in Wroclaw (Poland). Previously, each team member had various
      experience, in which chemistry played a major role. Dr. A. Gonciarz conducted
      spectroscopic research on coordination compounds, Prof. J. Zwozdziak is a well
      known expert in the field of environmental protection, and Prof. M. Zuber is an
      expert in the application of chemistry in security sciences. When they met at
      MULF, the idea of cooperation arose and their research interest was directed
      toward the possibility of practical application of Schiff bases and their
      complexes in various areas. Read the full text of their Full Paper at
      https://doi.org/10.1002/open.201800100.

PMID- 30191089
TI  - Steroid-responsive Encephalopathy Associated with Autoimmune Thyroiditis (SREAT)
      Presenting with Pure Cerebellar Ataxia.
AB  - Background: Myoclonus and tremor are common movement disorder phenomenologies in
      steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT).
      Pure ataxia without encephalopathy has rarely been reported. Case report: We
      report 21- and 40-year-old females who presented with subacute pure ataxia
      without encephalopathy. After immunotherapies, both exhibited initial improvement
      of ataxia, and subsequently remained in plateau phase. Discussion: This treatable
      disorder should be added to the differential diagnoses of progressive cerebellar
      ataxia, and anti-thyroid peroxidase and anti-thyroglobulin should be considered
      as part of the workup. It is crucial not to misdiagnose SREAT presenting with
      pure cerebellar ataxia as degenerative or spinocerebellar ataxia.

PMID- 30191087
TI  - Tardive Dyskinesia-like Syndrome Due to Drugs that do not Block Dopamine
      Receptors: Rare or Non-existent: Literature Review.
AB  - Background: Although tardive dyskinesia (TD) is most commonly defined as a
      movement disorder caused by chronic exposure to dopamine-receptor-blocking drugs
      (DRBDs), it has also been thought to result from exposure to some non-DRBDs.
      Methods: We critiqued many reviews making the association between non-DRBDs and a
      TD-like syndrome and almost all case reports. We checked whether cases met
      criteria for the diagnosis of TD-like syndrome and whether DRBDs had been
      excluded. Results: We found that both tricyclic antidepressants and selective
      serotonin reuptake inhibitor antidepressants may unmask or exacerbate TD after
      prior exposure to or with concurrent use of DRBDs. We found support for its
      existence outside of this context to be extremely weak. Discussion: There is
      little evidence that drugs other than DRBDs by themselves cause a TD syndrome;
      most reported cases appear to occur as a result of a "priming" effect induced by
      a DRBD, which is later unmasked.

PMID- 30191091
TI  - Over 50 % 1H and 13C Polarization for Generating Hyperpolarized Metabolites-A
      para-Hydrogen Approach.
AB  - para-Hydrogen-induced polarization (PHIP) is a method to rapidly generate
      hyperpolarized compounds, enhancing the signal of nuclear magnetic resonance
      (NMR) experiments by several thousand-fold. The hyperpolarization of metabolites
      and their use as contrast agents in vivo is an emerging diagnostic technique.
      High degrees of polarization and extended polarization lifetime are necessary
      requirements for the detection of metabolites in vivo. Here, we present pulsed
      NMR methods for obtaining hyperpolarized magnetization in two metabolites. We
      demonstrate that the hydrogenation with para-hydrogen of perdeuterated vinyl
      acetate allows us to create hyperpolarized ethyl acetate with close to 60 % 1H
      two-spin order. With nearly 100 % efficiency, this order can either be
      transferred to 1H in-phase magnetization or 13C magnetization of the carbonyl
      function. Close to 60 % polarization is experimentally verified for both nuclei.
      Cleavage of the ethyl acetate precursor in a 20 s reaction yields ethanol with
      approximately 27 % 1H polarization and acetate with around 20 % 13C polarization.
      This development will open new opportunities to generate metabolic contrast
      agents in less than one minute.

PMID- 30191093
TI  - Structures and Properties of LaFe0.8Cu0.2O3-delta and BaFe0.8Cu0.2O3-delta as
      Cobalt-Free Perovskite-Type Cathode Materials for the Oxygen Reduction Reaction.
AB  - Perovskite oxides with mixed electronic-ionic conduction are important catalysts
      for the oxygen reduction reaction in solid oxide fuel cells (SOFCs). Here, two
      cobalt-free perovskite oxides, LaFe0.8Cu0.2O3-delta (LFCuO) and BaFe0.8Cu0.2O3
      delta (BFCuO), were synthesized and comparatively studied with respect to their
      phase structures, oxygen contents, chemical defects, thermal expansion
      coefficient (TEC), as well as electrical and electrochemical properties.
      Different structures and properties have been found for each oxide, which have
      been interpreted based on their tolerance factors and chemical defects. LFCuO
      showed much better overall performance than BFCuO, and it proved to be a
      promising cobalt-free cathode material of intermediate-temperature SOFCs with a
      low TEC (12.0*10-6  degrees C-1) that matches well with TECs of the electrolytes,
      high catalytic activity for the oxygen reduction reaction characterized by low
      area specific resistances (0.090 Omega cm2 at 800  degrees C and 0.20 Omega cm2
      at 750  degrees C), and high-temperature chemical stability with electrolytes.

PMID- 30191092
TI  - Spectrochemical Properties and Solvatochromism of Tetradentate Schiff Base
      Complex with Nickel: Calculations and Experiments.
AB  - The nickel(II) complex with a tetradentate Schiff base ligand obtained by
      condensation of 1,3-propanediamine with salicylaldehyde (H2salpn) was studied in
      a variety of solvents at room temperature. The product, that is, the N',N''
      propylenebis(salicylaldiminato)nickel(II) ([Ni(salpn)]) complex, is brown in
      color in the solid state. The properties of the ligand and complex were
      characterized by elemental analysis, solubility in common solvents, molar
      conductivities, and ultraviolet (UV) and visible (Vis) spectroscopy. The
      [Ni(salpn)] complex is easily soluble in common solvents such as chloroform,
      methanol, ethanol, dimethyl formamide, dimethyl sulfoxide, acetonitrile, dioxane,
      acetone, 2-propanol, and toluene-a necessary condition for observing
      solvatochromism. The molar conductivity values, equal to 0.0 S mol-1 cm2 in these
      solvents, point to a typical non-electrolyte behavior for this complex.
      Spectroscopic measurements were used to confirm the square-planar geometry of the
      species in solution and to determine the coordination properties of the donor
      atoms and their bonding abilities (CFM/AOM parameters), as well as
      trichromaticity coordinate calculations. The results obtained show that the
      interactions of the metal with the donors depend on the polarity of the solvent.

PMID- 30191094
TI  - Health-related quality of life as a longitudinal mediator of the relationship
      between participation in organised sports and adiposity among young people.
AB  - The objective of this study was to investigate potential mediating effects of
      health-related quality of life between children's participation in organised
      sports and measures of adiposity. The sample consisted of 4116 children derived
      from the Longitudinal Study of Australian Children. Participants were aged 10.32
      (SD = 0.47) years at baseline (2010), and followed up 24 and 48 months later.
      Participation in organised sports was assessed using child-completed time-use
      diary. Health-related quality of life and demographic data were reported by each
      child's primary parent. Measures of body mass index, body fat, and waist
      circumference were also taken at each Wave. Sport was indirectly associated with
      measures of body fat (beta = -0.002, 95%CI -0.004, 0.000, p = .039) and waist
      circumference (beta = -0.001, 95%CI -0.003, 0.000, p = .039) through the
      mediating effects of social functioning. Sport was also associated with body fat
      via physical functioning (beta = -0.01, 95%CI -0.02, -0.003, p = .038), however,
      this was not replicated with other measures of adiposity. No other mediating
      effects were evident. Sport participation may enable children and adolescents to
      function well in groups and access social support which in turn promote health
      behaviours and influence adiposity. This may be one of multiple pathways through
      which sports participation is associated with adiposity. Replication and
      extension of these novel findings is warranted, as is a focus on the design and
      implementation of sports programs to maximise health benefits.

PMID- 30191095
TI  - Relationships among physical activity, sleep duration, diet, and academic
      achievement in a sample of adolescents.
AB  - The purpose of this study was to examine the relationships among physical
      activity, sleep duration, diet, and academic achievement in a sample of
      adolescents from the US state of Nevada. A two-stage cluster random sampling
      method was used to recruit Nevadan adolescents (N = 4625). The 2015 Youth Risk
      Behavior Survey was administered to students within public, private, and charter
      schools. Weighted multilevel generalized linear mixed effects models were
      employed to examine the relationships among physical activity, sleep duration,
      diet, and academic achievement. Additional analyses were run to examine the
      relationship between meeting multiple health behavior criteria with academic
      achievement. Data were collected in the US state of Nevada in 2015 and analyzed
      in the US state of Nevada in 2018. Adolescents who participated in at least of 60
      min of physical activity per day had significantly higher odds of achieving
      mostly A's and B's (adjusted OR = 1.18; 95% C.I.: 1.02, 1.38; p = 0.029).
      Additionally, adolescents who consumed salad weekly (adjusted OR = 1.24; 95%
      C.I.: 1.06, 1.46; p = 0.007) and who consumed breakfast everyday (adjusted OR =
      1.72; 95% C.I.: 1.48, 2.00; p < 0.001) had higher odds of achieving mostly A's
      and B's. Finally, adolescents who reported meeting 3 or more health behavior
      criteria had significantly higher odds of achieving mostly A's and B's compared
      to adolescents meeting only 0-2 health behaviors (adjusted OR = 1.66; 95% C.I.:
      1.44, 1.92; p < 0.001). Self-reported physical activity, specific dietary
      behaviors, and meeting multiple health behavior criteria significantly related to
      academic achievement in adolescents.

PMID- 30191096
TI  - A new measure of youth cigarette smoking.
AB  - American students' 30-day smoking prevalence has decreased dramatically over the
      past two decades. The frequency of smoking within the 30-day measure has shifted
      from heavy smoking (>1/2 pack/day) toward light smoking (<1 to 5 cigarettes/day).
      30-day prevalence thus understates the extent of the decline in youth smoking. To
      capture this shift toward less frequent smoking among the decreasing proportion
      of students who smoke, I develop a new index: the average number of cigarettes
      smoked per student per day (ACSD), using data from Monitoring the Future. To
      calculate ACSD I assign a specific number of cigarettes to each of 7 response
      options to the question, "How frequently have you smoked cigarettes during the
      past 30 days?" Response options range from "not at all" (assigned 0 cigarettes)
      to "two packs or more per day" (assigned 45 cigarettes). I then multiply these
      estimates by the proportion of students giving each response option. Summing
      across the 7 categories produces the ACSD for that survey year. I then compare
      time trends in 30-day prevalence and ACSD. From the mid-1990s to 2016, 30-day
      smoking prevalence among 12th graders declined 71.3%, while ACSD dropped 83.9% (p
      < 0.001). The figures were 84.0% and 90.6% (p < 0.001) for 10th graders and 87.4%
      and 89.0% for 8th graders (p < 0.05). Sensitivity analysis supports the finding
      that ACSD has decreased more than 30-day prevalence over time for both 10th and
      12th grades. ACSD provides a new measure of the decline in youth smoking to
      complement the traditional measure of 30-day prevalence.

PMID- 30191097
TI  - A randomized controlled trial in Norwegian pharmacies on effects of risk alert
      and advice in people with elevated cardiovascular risk.
AB  - We investigated if alerting subjects to elevated total cholesterol (TC),
      hemoglobin A1c (HbA1c) and blood pressure (BP) (cardiovascular disease (CVD) risk
      factors that are usually asymptomatic), and if providing advice would result in
      reduced risk. We conducted a multicenter (50 community pharmacies) parallel three
      arm 8-week randomized controlled trial (RCT) with a 52-week follow-up visit.
      During six days of screening, TC, HDL- and LDL-cholesterol, triglycerides, HbA1c,
      BP and body mass index (BMI) were assessed in 1318 individuals. Of these, 582
      with a measured and predefined elevated ad hoc CVD risk score were randomized to
      either Alert/advice (n = 198) (immediately alerted of their screening result and
      received healthy lifestyle-advice), Advice-only (n = 185) (received only advice)
      or Control (n = 199) (not alert, no advice). Changes in risk score and self
      reported health-related behaviors (diet, alcohol, physical activity) were
      assessed in pharmacies after 8 weeks (N = 543; 93%). Although the primary
      analysis showed no significant difference between groups, the Control group had
      the largest reduction in risk score of 14%. The total (uncontrolled) sample (N =
      543) reduced the risk score by 3.2% beyond estimated regression towards the mean
      and improved their health-related behaviors. Among the 65% (n = 377) who returned
      52 weeks after baseline, 14% reported started using CVD preventive medication
      after the screening. The study demonstrated that while assessing risk factors and
      behaviors in pharmacies proved efficient and possibly led to a small risk
      decrease, alerting people to their screening result did not seem to be more
      effective than a self-directed approach. ClinicalTrials.gov identifier:
      NCT02223793.

PMID- 30191098
TI  - Authors' awareness of concepts in the authorship of scientific publications:
      Viewpoints of the dental faculty in India.
AB  - Background: There is a great deal of enthusiasm amongst the contemporary dental
      academicians and researchers to publish their research findings and interesting
      cases. The competitive atmosphere has fostered a 'publish or perish' sentiment
      following which authors sideline certain essential and valid concepts in
      authorship and at times resort to unethical behavior knowingly or unknowingly to
      expand their publication list. Materials and method: We attempted to assess the
      current knowledge of the Indian dental teaching faculty regarding some important
      basic concepts in scientific authorship by means of a questionnaire-based pilot
      study. The respondents were asked questions pertaining to their knowledge of
      terms such as "authorship criteria", "conflict of interest", "plagiarism", and
      other authorship issues. Results: Our findings suggested significant lacunae
      regarding the authors' understanding of important basic concepts in scientific
      writing. Conclusion: We suggest possible measures to address this concern and
      also aim to survey a larger section of the academia in the future.

PMID- 30191099
TI  - Assessment of primary stability of the implant placed in prepared infected
      extraction sockets.
AB  - Background: Dental conditions like periodontal, periapical pathologies and failed
      endodontically treated teeth are one of the commonest reasons for tooth removal.
      These conditions also contraindicate replacement of such teeth with immediate
      implant procedures. Aim: This study aimed to evaluate the clinical and
      radiological fate of immediately placed dental implants in debrided infected
      dentoalveolar sockets. Materials and methods: A total of 24 implants were
      immediately placed into prepared infected sockets. The pathology at the
      receptacle sockets included subacute periodontal infection, perio-endo infection,
      chronic periapical infection, periodontal cyst and traumatic infected teeth. The
      treatment protocol emphasized on meticulous debridement of the infected sockets
      under pre- and post-surgical antibiotic therapy. Follow up of at least 24 months
      was done to evaluate the survival of implants. Results: At the end of follow up
      time period of 24 months, all 24 implants were stable with no signs of clinical
      mobility and infection. However, on radiological examination, crestal bone loss
      was observed during the osseointegration periods which settled at the level of
      first thread. Conclusion: Survival of immediately placed implants in infected
      sockets is predictable and depends on the meticulous debridement of dentoalveolar
      sockets along with adequate pre- and post-operative antibiotic coverage.

PMID- 30191100
TI  - Salivary glucose levels and oral candidal carriage in Type 2 diabetics.
AB  - Background: To assess the correlation between salivary glucose and blood glucose
      levels in diabetics and non diabetics and to study the association between
      salivary glucose levels and oral candidal carriage in patients with Type 2
      diabetes mellitus. Material and method: The study sample was divided into two
      groups, control and study group. The study group was again divided into two
      separate groups controlled diabetics and uncontrolled diabetics. Blood and saliva
      samples (for fasting and postprandial) were taken from each individual. Results:
      The salivary glucose levels, highly correlated with blood glucose levels in both
      diabetic as well as non diabetics subjects. Salivary candidal carriage was more
      in oral cavity of Type 2 diabetic subjects than control subjects. Conclusion:
      Saliva has the potential to be used as a noninvasive tool to monitor glycemic
      status of diabetic patients.

PMID- 30191101
TI  - Cyclosporine-A induces endoplasmic reticulum stress in human gingival fibroblasts
      - An in vitro study.
AB  - Drug induced gingival overgrowth is one of the side effects affecting the gingiva
      due to administration of certain systemic drugs. Cyclosporine A is one such drug
      which is commonly used in organ transplant conditions. The resultant overgrowth
      is fibrotic and extensive in nature which could impair patient esthetics and
      masticatory function. Endoplasmic reticulum stress is a recently identified
      phenomenon implicated in other fibrotic pathologies such as lung and renal
      fibrosis. In fact, endoplasmic reticulum stress has been known to play an
      important role in cyclosporine A induced renal fibrosis. Thus in this study, we
      sought to identify it's role in drug induced gingival overgrowth.

PMID- 30191102
TI  - Effect of oral health education by audio aids, Braille & tactile models on the
      oral health status of visually impaired children of Bhopal city.
AB  - Background: Braille is important language for reading & writing for the visually
      impaired. It helps them understand & visualize the world via touch. Audio aids
      are being used to impart health education to the visually impaired. Audio aids
      are useful in being time saving & can be played repeatedly to achieve desired
      results. Tactile models help them perceive things which they can't visualize &
      hence are important learning tool. Aim: To evaluate the effect of Oral Health
      education by Audio aids, Braille & tactile models on the Oral health status of
      visually impaired children of Bhopal city. Material & Methods: Sixty visually
      impaired children aged 5-18 yrs were selected & randomly divided into three
      groups (20 children each). Group A: Audio aids + Braille, Group B: Audio aids +
      tactile models, Group C: Audio aids + Braille + Tactile models. Instructions were
      given for maintaining good oral hygiene & brushing techniques were explained to
      all children. After three months time the oral hygiene status was recorded and
      compared using patient hygiene performance index. Results: The present study
      showed a decrease in the mean plaque scores (that is increase in mean difference
      of PHP score) at all time intervals in individual group as compared to the
      baseline that was statistically significant. Conclusion: The study depicts that
      the combination of audio, Braille & tactile models is an effective way to provide
      oral health education & improve Oral health status of visually impaired children.

PMID- 30191104
TI  - Role of Chemiluminescence examination as non-invasive diagnostic tool in early
      detection of Leukoplakia.
AB  - Objectives: To assess the efficacy of Chemiluminescent light (Vizilite plus) in
      enhancing visualization and its ability to highlight Leukoplakia lesion. Material
      and methods: This was a cross-sectional study done on 40 study subjects. Subjects
      were inducted into the study irrespective of age and sex based on the specific
      inclusion and exclusion criteria. The lesion parameters like the location of the
      lesion, the shape of lesion, the size, the extent, borders and the presence or
      absence of any adjacent satellite lesions were assessed under Incandescent light
      followed by Toluidine blue and Vizilite plus examinations. Histopathological
      examination results were considered as the gold standard and TBLU and CHEM
      outcomes were compared to them. Results: Vizilite plus examination method was
      most effective in assessing the size, borders and shape of the lesions followed
      by Toluidine blue and Incandescent light examinations. Toluidine blue and
      Vizilite plus examination methods demonstrated the sensitivity of 100% and
      specificity of 97.3%. They also demonstrated PPV of 100% and NPV of 75% with
      reliable accuracy of 97.5%. Conclusion: Chemiluminescent light is a stepping
      stone and has the potential to revolutionize the diagnostic protocol for patients
      with potentially premalignant lesions. The device can be used as a general oral
      mucosal examination system and may in particular improve the visualization of
      potentially premalignant lesions.

PMID- 30191103
TI  - Evaluation of graft uptake from the iliac crest in secondary alveolar bone
      grafting: Bergland's criteria revisited.
AB  - Back ground: The secondary alveolar grafting is an integral part in the
      management of alveolar cleft defect. Particulate cancellous bone and marrow
      (PCBM) graft obtained from iliac crest are considered as the gold standard. Aim:
      Aim of the study was to evaluate the graft uptake clinically and radiologically
      using the Bergland's radiographic scale. Material and methods: A longitudinal
      descriptive study was conducted on twenty patients of unilateral CLP in the age
      group of 6-13 years, presenting with residual/secondary alveolar cleft defect
      with unerupted maxillary lateral incisor/canine adjacent to the defect.
      Autologous PCBM graft obtained from iliac crest was used in all cases. Post
      operative clinical and radiological evaluation was carried out using the
      Bergland's radiographic scale at intervals of 1 week, 1 month and 6 months. Data
      collection and result: Clinical evaluation consisted of assessment for infection,
      exposure of graft, rejection of graft, wound dehiscence and status of oronasal
      communication. A four-point Bergland's radiographic scale was used to compare the
      interdental height of the bone graft with unaffected side and categorized from
      grade I to IV. After six months, 6 cases were graded as grade I, 11 cases as
      grade II and 2 cases were grade III. Only one case deteriorated to grade IV which
      is considered as failure. Summary and conclusion: Satisfactory results were
      obtained in 95% cases. Bergland's radiographic assessment scale is a valuable,
      easily available and inexpensive diagnostic tool to assess the condition of the
      grafted bone in SABG.

PMID- 30191105
TI  - Improving gingival zenith in a unilateral cleft patient using Platelet-Rich
      Fibrin (PRF).
AB  - This case evaluated the short term outcome of alveolar ridge augmentation in a
      unilateral alveolar cleft patient. A 22 year old female patient reported with
      gaps in her front teeth in 2011. Clinical examination revealed a repaired
      unilateral cleft of the hard palate (on left side) with a missing 21 and 22.
      Diagnosis was class II Subdivision with crossbite in 13 region. A non-extraction
      plan with a quad helix appliance, proximal stripping of lower anteriors. Canine
      substitution of 23 to replace 22 and prosthetic rehabilitation to replace 21. An
      alveolar ridge augmentation procedure using PRF (Platelet-rich fibrin) extracted
      from patient blood using a plasma centrifuge system. The success of grafted bone
      were evaluated radiologically at 6 months, 12 months postoperatively.

PMID- 30191106
TI  - Versatility of platelet rich fibrin in the management of alveolar osteitis-A
      clinical and prospective study.
AB  - Objective: To assess the efficacy of Platelet Rich Fibrin (PRF) on the pain and
      healing of the extraction socket associated with Alveolar Osteitis (Dry Socket,
      AO) after removal of maxillary and mandibular molars. Study design: 100 adult
      patients with age group ranging from 18 to 40 years along with established dry
      socket after maxillary and mandibular molar extractions who have not received any
      treatment for the same were included in the study. PRF was placed in the
      maxillary and mandibular molar extraction sockets after adequate irrigation of
      the socket. All the patients evaluated for the various study variables which
      include pain, degree of inflammation, and healthy granulation tissue formation at
      1st, 3rd, 7th, and 14th post operative day. Data were analyzed using
      Shapirowilk's test, chi square test and/or student-t test, Friedman's test,
      Wilcoxson's signed rank test, and Bonferroni test, with the significance level
      set at P < 0.05. Results: There was significant reduction in pain associated with
      AO at the 3rd and 7th postoperative day along with better wound healing by the
      end of 2nd week. Conclusion: Use of PRF in this study illustrates the promising
      results in terms of reduced pain and better healing in the patients with Alveolar
      Osteitits.

PMID- 30191108
TI  - Lymphatic malformation of the masseter: A case report.
AB  - Intramuscular vascular malformations are rare tumours occurring in less than 1%
      of skeletal muscles throughout the body, about 15% arising in the head and neck.
      Of these, lymphatic malformations are encountered to a lesser extent, being
      common in the tongue and the masseter being very rare. We present a case report
      of a lymphatic malformation of the masseter muscle in a 27 year old male. He
      presented with a swelling on his right cheek that had developed 1 year ago. Fine
      needle aspiration (FNA) of the lesion and Computed Tomography (CT) scans were
      done following which the provisional diagnosis of lymphatic malformation in the
      masseter was made. Surgical excision of the lesion was performed subsequently and
      histopathological examination confirmed the diagnosis. It is very rare to find a
      lymphatic malformation in the masseter and with such late presentation. Follow up
      should be done to note for potential recurrence.

PMID- 30191107
TI  - Research advances in Apert syndrome.
AB  - Apert syndrome is one of the several genetic syndromes associated with
      craniosynostosis, a condition that includes premature fusion of one or multiple
      cranial sutures. There has been significant clinical variation among different
      sutural synostoses and also within particular suture synostosis. Enormous
      progress has been made in identifying various mutations associated with Apert
      Syndrome. Although a causal gene has been defined, the precise role of this
      mutation in producing craniofacial dysmorphology and other related abnormalities
      is in the process of discovery. Most of the understanding regarding this rare
      disorder has been possible due to mouse models that have helped in deciphering
      the elements of this rare human disease. Thus, molecular and cellular
      understanding of the disease has taken a leap and further with the advent of
      technology definitive diagnosis of the syndrome is no more of an issue. In this
      review, we have discussed and consolidated the possible molecular studies that
      have contributed in understanding of this rare syndrome. This article may help
      clinicians and researchers to inform about the latest progress in Apert syndrome.

PMID- 30191109
TI  - Expansile radiolucent lesion of the Temporomandibular Joint-A diagnostic enigma.
AB  - Radiolucent lesions of Temporomandibular Joint (TMJ) represent a diagnostic
      challenge and a treatment conundrum. Biopsy of the lesions is technically
      difficult owing to their complex anatomy. The Differential Diagnosis (DD)
      includes a wide array of lesions including Simple Bone Cyst, Ameloblastoma,
      Central Giant Cell Granuloma, Hemangioma, Osteoblastoma, Osteochondroma,
      Chondroblastoma, Chondrosarcoma, Neurofibroma and metastatic malignant lesions
      though none has a specific predilection for TMJ. Here we present a case report of
      a large expansile radiolucent lesion of right TMJ in a 22 year old male patient
      with difficulties involved in diagnosis and management. Though cystic lesion of
      TMJ is uncommon it is incumbent on the Maxillofacial Surgeon for an early
      diagnosis and prompt management.

PMID- 30191111
TI  - Curvature height and distance of MB canal of mandibular molar with Schneider
      angle and its comparison with canal access angle.
AB  - Aim: To measure the proposed curvature height and distance of MB canal of
      mandibular molar with Schneider angle and its comparison with canal access angle
      both before and after instrumentation, and to compare among each other with
      multiple linear regression analysis. Methodology: One hundred human mandibular
      first and second molars were used for the study. After endodontic access, a size
      10 k-file was placed in the mesiobuccal canal extending to the apical foramen and
      radiographs were taken by using Radiovisiography. Both Schneider and canal access
      angle with its respective linear counterpart (Curvature height and curvature
      distance) was measured and calculated by using PLANMECA romexis (Helsinki
      Finland) software connected to the Intraoral x-ray unit both before and after
      biomechanical preparation with mesiobuccal canal till size F2. Statistical
      analysis was done by using multiple linear regression analysis. Results: A
      significant difference was observed between before and after enlargement with
      respect to Schneider angle and Canal access angle with a t-value being (t =
      11.0629, p < 0.05) (t = 10.5773, p < 0.05) for before and after enlargement of
      canals respectively. Percent of change is observed more with curvature height
      (29.62%) as compared with the curvature distance (8.87%). Conclusions: Schneider
      angle with its proposed curvature height and distance reduced after
      instrumentation. Whereas canal access angle decreased and its curvature height
      and distance have increased after instrumentation.

PMID- 30191110
TI  - Polarized microscope assisted study of collagen fibres in Oral Submucous Fibrosis
      and their clinicopathologic correlation: An in-vitro study.
AB  - Background: The present study was aimed to evaluate and analyze orientation and
      birefringence pattern of collagen fibers histopathologically in different grades
      of OSMF using the special stain (Picrosirius red) under polarizing microscope and
      relate these factors with the severity of OSMF. Materials and Method: 45
      confirmed cases of OSMF were taken from the archives. The selection of clinical
      cases was done according to classification by J.N Khanna and Andrade (1999).
      These cases were correlated histopathologically as per the criteria given by
      Pindborg J.J and Sirsat S.M (1966). The sections were stained with H & E and
      Picrosirius red stains and assessment was done accordingly. 10 cases of normal
      mucosa were taken as control. Results: In clinical grade I, 60% of the cases
      showed histopathological grade II, while 53.4% cases in clinical grade II
      correlated with histopathological grade III and 33.4% of clinical grade III cases
      showed histopathological grade IV. Upon application of Fisher's exact test a
      significant P value <.01 was obtained suggesting no statistical significant
      correlation between these two parameters. However, the orientation pattern
      revealed a parallel orientation as OSMF advanced. Also as the severity of the
      disease increased, there was a gradual shift from green- greenish yellow colour
      of the fibres and a shift to orange red-red colour. Conclusion: Upon correlation
      of clinical grades with histopathological grades, no statistically significant
      difference was found. Birefringence pattern of collagen revealed similar findings
      as other studies in case of clinical grades but histopathological grades showed a
      contrast finding.

PMID- 30191112
TI  - Catheterization of post infection parotid duct sialocele with paediatric Ryles
      tube: A case report.
AB  - Sialocele is a cavity filled with saliva, usually as a result of trauma,
      complication of surgery, sialolithiasis or bacterial infection residing inside
      the duct. Many cases of parotid sialocele have been reported in the literature,
      but only very few cases of parotid duct sialocele have been reported. We report a
      case of an unusual facial swelling over buccal mucosa at the route of Stenson's
      duct with poor oral hygiene, a case of parotid duct sialocele with secondary
      infection and describe its diagnosis and management.

PMID- 30191113
TI  - Evaluation of fracture toughness of zirconia silica nano-fibres reinforced
      feldespathic ceramic.
AB  - Background: Dental ceramics exhibit great optical properties and better esthetics
      due to their translucency. Concern with this material is its brittleness, which
      accounts for its failure. Feldspathic ceramic is the most widely used veneering
      ceramic. Aim and objectives: To evaluate and compare the fracture toughness of
      pressable feldspathic ceramics reinforced with zirconia silica nano-fibres with
      conventional pressable feldspathic ceramics. Materials and method: According to
      ISO 6872, a master die was prepared from which, Bar shaped samples were formed in
      acrylic resin with the specified dimensions of 4.0 mm in width *1.2 mm thickness
      *25.0 mm. The zirconia silica nano-fibres were prepared by sol gel electro
      spinning followed by calcination then they were incorporated into feldspathic
      ceramic through ball milling process. The samples were prepared with addition of
      0, 2.5, 5, 7.5 weight % nano-fibres. The fracture toughnes was evaluated using
      the indentation strength method. The values were statistically analysed using the
      one sample Kolmogorov-Smirnoff test, Kruskal Wallis test and pair wise group
      comparison was done using Mann Whitney test with Bonferroni correction. Results:
      The fracture toughness values for 2.5 wt% and 5 wt% groups were higher than
      control group, while the values for 7.5 wt% groups were lower compared to control
      group. Conclusion: The fracture toughness values of feldspathic ceramic samples
      reinforced with zirconia silica nanofibers by 2.5 and 5 wt% were statistically
      significant when compared to samples reinforced with 7.5 wt%.

PMID- 30191114
TI  - Genotypic characterization of Streptococcus mutans in child-mother pair-A PCR
      based study.
AB  - Objectives: At present, there is lack of evidence in literature regarding the
      transmission of Streptococcus Mutans from a caries-free mother to child by
      genetic methods, so the present study aimed to identify the genetic
      characterization of Streptococcus Mutans strains isolated from caries-free and
      caries active children and their mother being caries-free in both the groups and
      also to identify the genetic patterns of Streptococcus Mutans between caries-free
      and caries-active individuals. Methods: Twenty child-mother pair were selected
      and divided into 2 groups and the mothers being caries-free in both the groups.
      Saliva samples were collected using a sterile tube, followed by microbial culture
      of Streptococcus mutans, DNA isolation and PCR amplification. The molecular
      weights of each band were converted into a binary data and data were entered into
      SPSS software version 20.0 to generate similarity dendrograms. Results: Amplified
      products of Streptococcus Mutans demonstrated a same genetic distance between the
      mother-child pair, indicative of a closely related species. Dendrogram
      interpretation represented a greater genetic polymorphism of Streptococcus Mutans
      between caries-free and caries-active children. Conclusions: Identical genetic
      distance between child-mother pair showed that, these Streptooccus Mutans were
      closely related and could have vertically transmitted from their mothers.
      Different genotypic pattern between caries-free and caries active subjects showed
      a genetic polymorphism among the Streptococcus Mutans strains.

PMID- 30191115
TI  - Lip repositioning, an alternative treatment of gummy smile - A case report.
AB  - The aim of present case report is to discuss surgical lip repositioning technique
      for the management of excessive gingival display related with vertical maxillary
      excess and increase mobility of the upper lip. By restricting the muscle pull by
      elevator lip muscles, this procedure reduces excessive gingival display during
      smiling. For patient, this procedure is safe, less invasive with minimal side
      effects and an alternative to orthognathic surgery in the correction of gummy
      smile.

PMID- 30191116
TI  - Correlation of mitosis obtained by using 1% crystal violet stain with Ki67LI in
      histological grades of oral squamous cell carcinoma.
AB  - Aim: The purpose of this study was to use a simple, cost-effective technique for
      studying mitosis in various grades of oral squamous cell carcinoma (OSCC) using
      1% Crystal-violet stain and to correlate mitotic frequency index (MFI) obtained
      by it with Ki67 labeling index (Ki67LI) so as to validate its usefulness as a
      selective stain for evaluating proliferation. Materials and Methods: The invasive
      front grading score (IFG Score) was recorded in 40 patients of OSCC. Mitotic
      figures were assessed in hematoxylin and eosin (H and E) stained section as well
      as in 1% crystal-violet stained section using MFI (MFI = Mitosis/total number of
      cell counted X100). Comparison between MFI obtained by 1% crystal violet stain
      and H and E stain was done. Ki67LI was assessed using Ki67 immunohistochemical
      (IHC) marker. Correlation between Ki67LI and MFI obtained by using 1% crystal
      violet stain was performed. Results: There was statistically significant increase
      in MFI obtained by using 1% crystal-violet stain compared to routine H and E
      stain. Statistically significant positive correlation was observed between Ki67LI
      and mitosis in well and moderately differentiated OSCC. Positive correlation was
      also observed in poorly differentiated OSCC, but it was not statistically
      significant. Both mean MFI and mean Ki67LI significantly increased from grade I
      to grade II to grade III OSCC. Conclusion: 1% crystal violet stain provides a
      definite advantage over the H and E stained sections. Thus crystal violet stain
      is easy and cost effective to evaluate proliferation when compared with expensive
      proliferative IHC marker.

PMID- 30191117
TI  - Prevalence of congenital cardiac anomalies in patients with cleft lip and palate 
      Its implications in surgical management.
AB  - Background: Cleft lip and palate is one of the most common congenital
      craniofacial deformities seen in children. Various congenital anomalies are
      reported in the literature to be associated with cleft lip and palate. Cardiac
      anomalies are one of the most common congenital disorders associated in cleft lip
      and palate patientsIt includes Cyanotic and acyanotic cardiac diseases likel
      fallot's tetralogy, transposition of greater vessels, atresia of tricuspid, total
      anomalous pulmonary venous return (TAPVR), truncus arteriosus, ebstein's anomaly,
      hypoplastic left heart syndrome and pulmonary atresia, patent ductus arteriosus,
      ventricular septal defect, atrial septal defect, pulmonary stenosis, aortic
      stenosis and coarctation of aorta. Aim: To study the prevalence of congenital
      cardiac anomalies in cleft lip and palate patients. Objectives: To study
      different types of congenital cardiac anomalies/defects in patients with cleft
      lip and palate and its implications in surgical management. Materials and
      Methods: This is a retrospective study carried out for a period of one year. In
      the present study medical records of 200 patients with cleft lip and palate were
      evaluated and analyzed for presence of congenital cardiac anomalies. Results: Out
      of 200 patients of cleft lip and palate, 30 patients (15%) were associated with
      congenital cardiac anomalies with male to female ratio of 1:1. Associated
      congenital cardiac anomalies were most frequently seen in unilateral cleft palate
      patients (21.05%) The most common cardiac anomaly was Ventricular septal defect
      (36.6%).

PMID- 30191119
TI  - Borle's triangle: A reliable anatomical landmark for ease of identification of
      facial nerve trunk during parotidectomy.
AB  - Purpose: An accurate understanding of the anatomy, identification and
      preservation of facial nerve is critical in performing successful functional
      parotidectomies. The current literature is replete with inconsistencies of
      various landmarks when used alone for identification of facial nerve trunk (FNT).
      The purpose of the paper is to introduce a new anatomical triangle, Borle's
      triangle (BT) for safer and reliable operative identification of FNT during
      parotodectomies. Patients and methods: Between Aug 2014 and Dec 2017, twelve
      patients who reported with unilateral disease of the parotid gland with intact
      facial nerve function who underwent superficial or complete parotidecomies were
      included in the study. BT was conceptualized by intersection of three imaginary
      lines drawn along anatomical structures and forming a triangle comprising of
      angles a, b and c. Results: Introperatively, BT helped reliably identify the FNT
      and its branches successfully in all the cases. The mean distance of FNT from
      angle b was found to be 12.18 +/- 1.7 mm. Transient neurological deficits with
      one or more branches were seen in four cases whilst, one case had transient
      deficit with all the five peripheral branches. All of them spontaneously resolved
      completely by the end of three months post operatively. Conclusions: When used in
      isolation, substantial variations exist in distances measured from anatomic
      landmarks to the main FNT in the literature. The BT utilizes three commonly used
      anatomical landmarks. It predictably helps in proper anatomic orientation,
      identification and preservation of FNT and branches with ease in parotidectomies.

PMID- 30191118
TI  - Natural agents in the management of oral mucositis in cancer patients-systematic
      review.
AB  - Introduction: Oral mucositis is most severe complication of cancer therapy
      characterized by ulcerative lesions of oral mucosa causing negative impact on
      patient's quality of life. Wide variety of therapeutic agents are available to
      reduce the lesions of mucositis. Currently, natural herbal remedies have become
      popular in treating this condition due to fewer side effects than synthetic
      drugs. Aim: The aim of this systematic review is to compile evidence based
      studies to evaluate the effectiveness of natural agents in the management of oral
      mucositis induced by chemotherapy or radiotherapy in cancer patients. Materials
      and method: Computerized literature searches were performed to identify all
      published articles in the subject. The following databases were used: PUBMED
      [MEDLINE], SCOPUS, COCHRANE DATABASE, EMBASE and SCIENCE DIRECT using specific
      keywords. The search was for limited articles published in English which were
      read in full by two authors. Results: Twenty six randomized controlled trials
      satisfied our inclusion criteria. Most studies showed statistically significant
      result demonstrating the efficacy of natural agents with minimal side effects
      except manuka honey which was not tolerated by few patients. Conclusion: Natural
      agents proved to be promising in healing cancer induced oral mucositis but future
      demands further randomized controlled clinical trials on these agents which
      should also be focused on drug interactions of the natural remedies.

PMID- 30191120
TI  - Primary antiphospholipid syndrome associated Liebman-Sachs endocarditis leading
      to diffuse alveolar hemorrhage: A case report.
AB  - A 26 year old female presented for recurrent blood tinged sputum during the
      previous year with development of frank hemoptysis three days prior to admission.
      Diffuse alveolar hemorrhage (DAH) was confirmed with serial lavages. The patient
      had no history of autoimmune disease, vascular thrombosis or pregnancy morbidity
      including miscarriages or pre-eclampsia. High dose steroids were initiated along
      with noninvasive ventilatory support. Transthoracic echocardiogram showed severe
      mitral regurgitation and a vegetation on the mitral valve; transesophageal
      echocardiogram determined the lesion highly suggestive of Libman-Sachs
      endocarditis. Blood cultures were negative. Immunological evaluation established
      the patient was negative for: anti-nuclear antibody, anti-double-stranded DNA
      antibody, rheumatoid factor, anti-smith antibody, anti-cyclic citrullinated
      peptide, anti-neutrophil cytoplasmic antibodies, anti-glomerular basement
      membrane antibodies. Further evaluation revealed elevated levels of
      anticardiolipin immunoglobulin G and anti-beta 2 glycoprotein immunoglobulin G
      which continued to increase for months after hospitalization. She was diagnosed
      with DAH secondary to acute mitral regurgitation caused by Libman-Sachs
      endocarditis in the presence of primary antiphospholipid antibody syndrome. DAH
      is an important disease to understand given its high mortality rate. Few case
      reports relating the presence of Libman-Sachs endocarditis induced by
      antiphospholipid antibody syndrome leading to DAH have been published. Unique
      here is the absence of rheumatologic markers thus supporting a diagnosis of
      primary antiphospholipid antibody syndrome (APS). This patient had no findings
      associated with rheumatological disorders potentially making this diagnosis
      easily overlooked. This case further illustrates the importance of evaluating
      patients with APS presenting with DAH as there are multiple etiologies that lead
      to this pathology thus different treatment avenues are to be considered during
      management.

PMID- 30191121
TI  - Migrating gossypiboma mimicking aspergilloma twenty years after mediastinal
      surgery.
AB  - A gossypiboma refers to a surgical sponge or gauze accidentally retained inside a
      patient during a procedure. It is more commonly encountered after abdominal
      surgeries. When seen in the thorax, it is usually located within the pleural
      cavity. We report a case of a 42-year old woman who was found to have a
      gossypiboma mimicking a simple aspergilloma twenty years after a left
      thoracotomy. The surgical gauze identified on a CT-scan of her chest appears to
      have migrated into her lung airways.

PMID- 30191122
TI  - Bordetella bronchiseptica in non-cystic fibrosis bronchiectasis.
AB  - Bordetella bronchiseptica is a rare pulmonary infection, often associated with
      zoonotic transmission. It has been described in immunocompromised patients and
      those with underlying pulmonary disease. However, there are no case series
      describing the spectrum of disease caused by Bordetella bronchiseptica in
      patients with non-cystic fibrosis bronchiectasis. Here, we report three cases of
      Bordetella bronchiseptica infection in patients with non-cystic fibrosis
      bronchiectasis and highlight the pathophysiology of the microbe. While the
      clinical presentation can be quite variable, it is important to note that
      Bordetella bronchiseptica can be a cause of pulmonary exacerbations and can be
      difficult to eradicate.

PMID- 30191123
TI  - A case of anti-melanoma differentiation-associated gene 5 antibody-positive
      interstitial lung disease complicated with tracheobronchial ulcers.
AB  - We herein report the first case, to our knowledge, of tracheobronchial ulcer with
      anti-melanoma differentiation-associated gene 5 (anti-MDA 5) antibody-positive
      interstitial lung disease (ILD). A 53-year-old man complained of shoulder and
      wrist pain and was suspected of having polymyalgia rheumatica at another
      hospital. Thereafter, treatment with prednisolone was started. Although his
      arthralgia improved, he suffered from progressive dyspnea on exertion and an
      abnormal shadow was noted on chest X-ray, so he was transferred to our hospital.
      Chest computed tomography scan revealed ground-glass opacities and intralobular
      septal thickening. We diagnosed him as having clinically amyopathic
      dermatomyositis associated with ILD based on the specific skin findings and
      elevated anti-MDA 5 antibody titer. Fiberoptic bronchoscopy showed ulcerations of
      the trachea and bronchus. Treatment with dose increments of prednisolone combined
      with other immunosuppressive drugs resulted in improvement of his respiratory
      condition and tracheobronchial lesions. Clinicians should be aware that
      tracheobronchial ulcers can be associated with anti-MDA 5 antibody-positive
      interstitial lung disease.

PMID- 30191124
TI  - Compromised prefrontal structure and function are associated with slower walking
      in older adults.
AB  - Our previous work demonstrates that reduced activation of the executive network
      is associated with slow walking speed in a cohort of older adults from the
      MOBILIZE Boston Study. However, the influence of underlying white matter
      integrity on the activation of this network and walking speed is unknown. Thus,
      we used diffusion-weighted imaging and fMRI during an n-back task to assess
      associations between executive network structure, function, and walking speed.
      Whole-brain tract-based spatial statistics (TBSS) were used to identify regions
      of white matter microstructural integrity that were associated with walking
      speed. The integrity of these regions was then entered into multiple regression
      models to predict task performance and executive network activation during the n
      back task. Among the significant associations of FA with walking speed, we
      observed the anterior thalamic radiation and superior longitudinal fasciculus
      were further associated with both n-back response speed and executive network
      activation. These findings suggest that subtle damage to frontal white matter may
      contribute to altered executive network activation and slower walking in older
      adults.

PMID- 30191126
TI  - Hemophagocytic lymphohistiocytosis (HLH) presenting as fever of unknown origin
      and acute liver failure.
AB  - A 51-year-old previously healthy woman presenting with two-weeks of fever, flu
      like symptoms, jaundice, and abdominal pain was found to have pancytopenia,
      transaminitis, and significantly elevated ferritin in the setting of an Epstein
      Barr Virus (EBV) infection. Bone marrow biopsy revealed phagocytic macrophages
      consistent with findings of hemophagocytic lymphohistiocytosis (HLH). Given bone
      marrow findings and that the patient had five of the eight clinical criteria
      supporting the diagnosis of HLH, chemotherapy was initiated as per the HLH-94
      protocol with initial improvement in patient's symptoms and overall functional
      status. This case demonstrates a classic presentation of HLH and displays the
      importance of correct diagnosis and prompt treatment.

PMID- 30191127
TI  - Chronic meningococcemia presenting with recurrent painful rash and poly
      arthralgia without fever.
AB  - Chronic meningococcemia is an uncommon disorder, representing a diagnostic
      challenge. Classically, this pathology would be considered in young adults with a
      history of episodes of fever, disseminated cutaneous vasculitis and arthralgia.
      Exact and rapid diagnosis is often further challenged by the fact that routine
      microbiological investigations frequently failed to identify incriminated micro
      organism, Neisseria meningitidis. Here we present the case of a young man not
      presenting with the classical triad.

PMID- 30191125
TI  - A case of interictal dysphoric disorder comorbid with interictal psychosis: Part
      of the same spectrum or separate entities?
AB  - Depressive disorders in epilepsy often present characteristic clinical
      manifestations atypical in primary, endogenous depression. Here, we report a case
      of a 64-year-old woman with right mesial temporal lobe epilepsy, who complained
      of bizarre, antipsychotic-refractory cenesthetic hallucinations in her interictal
      phase, and was hospitalized after a suicide attempt. Detailed clinical
      observations revealed mood symptoms, which led to the diagnosis of interictal
      dysphoric disorder comorbid with interictal psychosis. Sertraline with low-dose
      aripiprazole markedly alleviated both depressive and psychotic symptoms. This
      case suggested that the two diagnostic entities may overlap and that depressive
      symptoms tend to be concurrent when concurring with psychosis, which hampers the
      appropriate choice of a treatment option.

PMID- 30191128
TI  - Primary pulmonary Kaposi Sarcoma in a newly diagnosed cisgender heterosexual HIV
      positive patient presenting before cutaneous manifestations.
AB  - AIDS-related Kaposi sarcoma (KS) is a vascular malignancy that usually presents
      with mucocutaneous lesions. Bronchopulmonary involvement as an initial
      manifestation is a rare phenomenon. This case describes a young male presenting
      with pulmonary symptoms mimicking HIV-related opportunistic infection who was
      eventually diagnosed with primary pulmonary KS. The aim of this report is to
      emphasize that KS should be recognized as a differential diagnosis in AIDS
      patients presenting with pulmonary symptoms. Making the diagnosis may be a
      difficult task, at times, requiring invasive procedures such as lung biopsy.

PMID- 30191129
TI  - Hyperammonemic encephalopathy with septic shock caused by obstructive urinary
      tract infection.
AB  - A 61-year-old woman was evaluated because of 2 days of anuria, fever, anorexia,
      and progressive decline in mental status. On admission, she appeared confused
      with a GCS score of E2V2M4, and her blood ammonia level was elevated (176
      MUg/dL). Abdominal computed tomography showed bilateral hydronephrosis and
      bladder fullness with wall thickness in spite of indwelling bladder catheter. Her
      catheter was obstructed by blood clot. Blood cultures, blood clot culture, and
      one urine culture all yielded Proteus mirabilis. Obstructive urinary tract
      infection complicated with septic shock was diagnosed. After treatment, her
      ammonia level normalized.

PMID- 30191130
TI  - Cytomegalovirus acute infection with pulmonary involvement in an immunocompetent
      patient.
AB  - Introduction: Cytomegalovirus (CMV) infection in healthy adults is usually
      asymptomatic or causes a mild mononucleosis syndrome, while severe infections are
      rare in immunocompetent patients and poorly documented. When described,
      gastrointestinal tract and the central nervous systems are the most frequent
      sites of severe CMV infection. Lung disease can occur, but it's rare. Clinical
      case: A 29 years old man presenting with a 2-weeks history of fever, headache,
      malaise, dry non-productive cough and thoracic pleuritic pain, without
      improvement after one-week therapy with levofloxacin. Blood exams showed
      lymphocytosis of almost 50%, nine percent of atypical lymphocytes and elevated
      transaminases. Thoracic CT-scan showed bilateral infiltrate with internal air
      bronchogram. Blood serology showed positivity for CMV IgG and IgM, with low CMV
      IgG avidity. Serum and bronchoalveolar detection of CMV by polymerase chain
      reaction (PCR) technique was also positive. Cultures were all negative. The
      patient became increasingly hypoxemic and the liver transaminases worsening, the
      reason for which ganciclovir was started. He made a full recovery and was
      discharged seven days later with oral valganciclovir, completing a 3 weeks
      antiviral course at home. Discussion: CMV pneumonia is a rare condition, however
      it's one of the three most common cause of severe viral community acquired
      pneumonia (CAP), along with influenza and adenovirus. CMV pneumonia should be
      considered in patients with atypical lymphocytes and mildly elevated serum
      transaminases. Conclusion: In immunocompetent hosts, even with severe CMV-CAP,
      the prognosis is good. However, antiviral treatment should be considered in the
      rare occasion of severe CMV infection. Nevertheless, more studies are needed to
      clarify the clinical benefit of antiviral treatment.

PMID- 30191131
TI  - Acute hepatitis C from heterosexual transmission.
AB  - The diagnosis of acute hepatitis C (HCV) infection is rare since the majority of
      cases are asymptomatic, which makes the infection usually detected in a chronic
      phase, most of the time using serological tests. The main route of HCV
      transmission is percutaneous, with sexual transmission occurring more often in
      men who have sex with men. The analytical alterations of acute hepatitis C are
      varied but usually present with ALT elevation higher than AST, very rarely with
      hepatic insufficiency. We report a case of a patient with a clinical and
      analytical picture compatible with toxic acute hepatitis, accompanied by hepatic
      insufficiency, with negative serology for hepatotropic viruses and with no
      history compatible with the use of substances with hepatic toxicity other than
      alcohol. During the diagnostic investigation it was concluded that the patient
      had acute HCV hepatitis and that the transmission route was heterosexual.

PMID- 30191132
TI  - Milian's ear sign: Erysipelas.
AB  - A clinical case is presented here of a patient with fever and ear pain. Physical
      examination revealed "Milian's ear sign", which supports the diagnosis of
      erysipelas rather than cellulitis. After intravenous antibacterial treatment, the
      patient recovered.

PMID- 30191133
TI  - Hepatocellular carcinoma after direct-acting antiviral therapy for chronic HCV
      infection: Is it a real risk?
AB  - The newer oral treatments for chronic hepatitis C virus infection are one of the
      greatest revolutions in modern medicine. These drugs promise to eradicate the
      infection, showing high cure rates even in difficult to treat populations with
      very few side effects. Nevertheless, some cases of recurrence and de novo
      hepatocellular carcinoma after treatment with these drugs have been reported. We
      describe two cases of patients treated with direct-acting antiviral agents that
      developed hepatocarcinoma during follow-up post-treatment.

PMID- 30191135
TI  - Copper oxide nanoparticles induces oxidative stress and liver toxicity in rats
      following oral exposure.
AB  - The present study aimed to evaluate the effect of Copper Oxide (CuO)
      Nanoparticles (NP) on liver following oral exposure in rats. A total of 18 male
      wister rats were used in the experiments including a control group (6 rats). NP
      were given to the rats with a doses (5, 50 mg/kg b.w./day) via oral gavage and a
      control group (received only 200 MUl PBS). The treatment was continued for 14
      days. The supernatants of rat Liver tissue homogenates were used to analyze for
      glutathione levels (GSH), Catalase, superoxide dismutase (SOD), the extent of
      lipid peroxidation products (Malondialdehyde, MDA). Oral administration of NP to
      rats caused a significant (P < 0.05) dose dependent alterations in antioxidant
      enzyme activities. Data results clearly showed the significant decrease (p <
      0.05) in GSH, Catalase (CAT) and SOD activity, whereas the lipid peroxidation
      product (MDA) levels were increased (p < 0.05). In conclusion, oral exposure of
      CuO nanoparticles to rats causes significant toxicity to the liver and it might
      be due to oxidative stress.

PMID- 30191134
TI  - Assessment of concentration and toxicological (Cancer) risk of lead, cadmium and
      chromium in tobacco products commonly available in Bangladesh.
AB  - This study aimed to assess the concentrations of heavy metal ('lead (Pb)''cadmium
      (Cd)', and 'chromium (Cr)') in various brands of four types of tobacco products
      (zarda, gul, cigarettes, and bidi) as well as calculate toxicological risk as a
      lifetime cancer risk for Pb, Cd, and Cr. In smokeless tobacco products, the metal
      concentration ranged from 0.99 to 10.02 MUg/g for Pb, 1.05-3.53 MUg/g for Cd, and
      1.23-7.29 MUg/g for Cr, respectively. Metal concentrations in the smoke-based
      tobacco products ranged from 0.98 to 3.07 MUg/g for Pb, 0.91-3.46 MUg/g for Cd,
      1.08-6.75 MUg/g for Cr, respectively. When assuming a 100% transfer of these
      metals, the calculated lifetime cancer risk was found 'unacceptable' in 33 out of
      35 tobacco samples which exceeded the U.S. Environmental Protection Agency
      (USEPA) benchmark of an 'acceptable' cancer risk range of 10E-4 to 10E-6. Our
      study demonstrated higher levels of Pb, Cd, and Cr in various tobacco products of
      Bangladesh compared to GOTHIATEK standard. This study shows the need for the
      development of industry standards and regulation for tobacco products to reduce
      the levels of heavy metals.

PMID- 30191136
TI  - Innovation for rare diseases and bioethical concerns: A thin thread between
      medical progress and suffering.
AB  - With the development of precision medicines based on small molecules, antibodies,
      RNAs and gene therapy, technological innovation is providing some exciting
      possibilities to treat the most severe genetic diseases. However, these
      treatments do not always lead to a cure for the disease, and there are several
      factors that may hinder their overall success. Patients living during a period of
      great medical change and innovation may benefit from these technological advances
      but may also just face failures, both in terms of frustrated hopes as well as
      suffering. In this article, we are telling the stories of three children with
      rare and severe disorders, who live in an age of significant medical changes,
      bearing the burden of difficult scientific and ethical choices. The first two
      cases that are suffering respectively from severe immunodeficiency and beta
      thalassemia have already been described in scientific journals, as well as in
      popular magazines. Although similar when considering the medical challenges, the
      two cases had opposite outcomes, which resulted in distinct ethical implications.
      The third case is a baby with spinal muscular atrophy, living at a time of
      continued innovation in the treatment of the disease. With these cases, we
      discuss the challenges of providing correct information and proper counseling to
      families and patients that are making the bumpy journey on the road of medical
      innovation.

PMID- 30191137
TI  - Clinical features of acute kidney injury in patients with Kawasaki disease.
AB  - Although acute kidney injury (AKI) is a common complication in hospitalized
      children, AKI has rarely been reported in patients with Kawasaki disease (KD).
      Herein, we review the clinical trajectories of AKI in patients with KD. A total
      of 39 patients with KD who developed AKI have been reported in 28 publications as
      case reports. The causes of AKI include prerenal AKI associated with acute heart
      failure (AHF), intrinsic AKI caused by tubulointerstitial nephritis (TIN), acute
      nephritic syndrome (ANS), hemolytic uremic syndrome (HUS), immune complex
      mediated nephropathy, rhabdomyolysis, and KD shock syndrome (KDSS). Six of the 39
      patients (15.4%) underwent renal replacement therapy. While AHF and multiple
      organ dysfunction syndrome developed in 41% and 68% of KD patients with AKI,
      respectively, all patients recovered without any renal sequelae. Although the
      precise pathogenic mechanism underlying the development of AKI in patients with
      KD is unknown, several possible mechanisms have been proposed, including T-cell
      mediated immunologic abnormalities for TIN, renal and glomerular endothelial
      injury resulting from vasculitis for HUS, immune complex-mediated kidney injury
      for immune complex-mediated nephropathy and ASN, and capillary leak and an
      increased release of cytokines with myocardial dysfunction for KDSS.

PMID- 30191138
TI  - Predictive markers of endocrine response in breast cancer.
AB  - Ongoing clinical and research efforts seek to optimise the use of endocrine
      therapy in the treatment of breast cancer. Accurate biomarkers are needed that
      predict response for individual patients. The presence of the estrogen receptor
      (ER) as the direct (for tamoxifen and fulvestrant) or indirect (for aromatase
      inhibitors) target molecule for endocrine therapy remains the foremost biomarker
      and determinant of response. However, ER expression only poorly predicts outcome
      and further indicators of response or resistance are required. The development
      and application of molecular signature assays such as Oncotype Dx, Prosigna,
      Mammaprint and Endopredict have provided valuable information on prognosis and
      these are being used to support clinical decision making on whether endocrine
      therapy alone alongside surgery is sufficient for ER-positive early stage breast
      cancers or whether combination of endocrine with chemotherapy are also warranted.
      Ki67, the proliferation marker, has been widely used in the neo-adjuvant (pre
      operative) setting to help predict response and long term outcome. Gene
      expression studies within the same setting have allowed monitoring of changes of
      potential predictive markers. These have identified frequent changes in estrogen
      regulated and proliferation genes. Specific molecules such as mutant ER may also
      prove helpful biomarkers in predicting outcome and monitoring response to
      treatment.

PMID- 30191139
TI  - Autonomic function and ventricular tachyarrhythmias during acute myocardial
      infarction.
AB  - Most cases of sudden cardiac death are attributed to sustained ventricular
      tachyarrhythmias (VTs), triggered by acute coronary occlusion. Autonomic
      dysfunction, an important arrhythmogenic mechanism in this setting, is being
      actively investigated, aiming at the advent of preventive strategies. Recent
      experimental studies have shown vagal withdrawal after anterior myocardial
      infarction, coinciding with high incidence of VTs, followed by more gradual
      sympathetic activation coinciding with a second arrhythmia peak. This article
      summarizes recent knowledge on this intriguing topic, generating hypotheses that
      can be investigated in future experimental and clinical studies.

PMID- 30191141
TI  - The Association Between Metabolic Syndrome and Gastric Cancer in Chinese.
AB  - Background: Metabolic syndrome (MetS) play a carcinogenic role in variety of
      cancers and influence the prognosis of cancer patients both systemically and
      hormonally. Methods: The data of clinicopathologic features and MetS of 808
      gastric cancer patients and 1,146 randomly healthy controls were analyzed
      retrospectively. Results: Higher TG level, lower HDL-C level and higher
      hypertension frequency were observed in all gastric cancer patients when compared
      with healthy controls. While, gastric cancer patients had greater waist
      circumference only in females. Among three definitions of MetS, the MetS
      identified by the Chinese Diabetes Society (CDS) was associated with the most
      significant increasing risk of gastric cancer. Comparing all gastric cancer
      patients with healthy controls, OR of gastric cancer was enhanced by various
      individual components of the MetS, including higher TG level, lower HDL-C level,
      hypertension and diabetes; In male subgroup, OR of gastric cancer was enhanced by
      higher BMI, hypertension and diabetes; In females, OR of gastric cancer was
      enhanced by lower HDL-C, hypertension and diabetes. MetS was associated with poor
      differentiated carcinoma, more advanced pathological T, N stage and TNM stage of
      gastric cancer. Conclusion: The presence of MetS and its components were
      increased in gastric cancer, especially in gastric cancer patients with poor
      differentiation and advanced stage, which implies that metabolic disorder may
      play an important role in the development of gastric cancer.

PMID- 30191142
TI  - Benzylamine and Thenylamine Derived Drugs Induce Apoptosis and Reduce
      Proliferation, Migration and Metastasis Formation in Melanoma Cells.
AB  - Melanomas are heterogeneous and aggressive tumors, and one of the worse in
      prognosis. Melanoma subtypes follow distinct pathways until terminal oncogenic
      transformation. Here, we have evaluated a series of molecules that exhibit potent
      cytotoxic effects over the murine and human melanoma cell lines B16F10 and MalMe
      3M, respectively, both ex vivo and in animals carrying these melanoma cells. Ex
      vivo mechanistic studies on molecular targets involved in melanoma growth,
      migration and viability were evaluated in cultured cells treated with these drugs
      which exhibited potent proapoptotic and cytotoxic effects and reduced cell
      migration. These drugs altered the Wnt/beta-catenin pathway, which is important
      for the oncogenic phenotype of melanoma cells. In in vivo experiments, male
      C57BL/6 or nude mice were injected with melanoma cells that rapidly expanded in
      these animals and, in some cases were able to form metastasis in lungs. Treatment
      with anti-tumor drugs derived from benzylamine and 2-thiophenemethylamine
      (F10503LO1 and related compounds) significantly attenuated tumor growth, impaired
      cell migration, and reduced the metastatic activity. Several protocols of
      administration were applied, all of them leading to significant reduction in the
      tumor size and enhanced animal survival. Tumor cells carrying a luciferase
      transgene allowed a time-dependent study on the progression of the tumor.
      Molecular analysis of the pathways modified by F10503LO1 and related compounds
      defined the main relevant targets for tumor regression: the activation of pro
      apoptotic and anti-proliferative routes. These data might provide the proof-of
      principle and rationale for its further clinical evaluation.

PMID- 30191143
TI  - Prospect of Circular RNA in Hepatocellular Carcinoma: A Novel Potential Biomarker
      and Therapeutic Target.
AB  - CircRNA, a kind of tissue specific and covalently closed circular non-coding RNA
      is very abundant in eukaryocyte. Generally, circRNA is generated by back-splicing
      of protein-coding genes' pre-mRNA. Hepatocellular carcinoma (HCC) is one of the
      most common malignant tumors in the world. Due to the characteristics of poor
      prognosis and high recurrence, the pathogenesis of HCC is highly concerned by
      researchers worldwide. Recent studies demonstrated that numerous circRNAs were
      differentially expressed in HCC tissues and normal liver tissues, which is
      closely related with the development and prognosis of HCC. However, the mechanism
      of circRNA in HCC remains unclear. In this review, we summarized the abnormal
      expressions of circRNAs in HCC, discussed its role, and potential mechanisms, and
      tried to explore the prospective values of circRNA in the diagnosis, therapy, and
      prognosis of HCC.

PMID- 30191140
TI  - Immuno-Oncology: Emerging Targets and Combination Therapies.
AB  - Host immunity recognizes and eliminates most early tumor cells, yet immunological
      checkpoints, exemplified by CTLA-4, PD-1, and PD-L1, pose a significant obstacle
      to effective antitumor immune responses. T-lymphocyte co-inhibitory pathways
      influence intensity, inflammation and duration of antitumor immunity. However,
      tumors and their immunosuppressive microenvironments exploit them to evade immune
      destruction. Recent PD-1 checkpoint inhibitors yielded unprecedented efficacies
      and durable responses across advanced-stage melanoma, showcasing potential to
      replace conventional radiotherapy regimens. Neverthless, many clinical problems
      remain in terms of efficacy, patient-to-patient variability, and undesirable
      outcomes and side effects. In this review, we evaluate recent advances in the
      immuno-oncology field and discuss ways forward. First, we give an overview of
      current immunotherapy modalities, involving mainy single agents, including
      inhibitor monoclonal antibodies (mAbs) targeting T-cell checkpoints of PD-1 and
      CTLA-4. However, neoantigen recognition alone cannot eliminate tumors effectively
      in vivo given their inherent complex micro-environment, heterogeneous nature and
      stemness. Then, based mainly upon CTLA-4 and PD-1 checkpoint inhibitors as a
      "backbone," we cover a range of emerging ("second-generation") therapies
      incorporating other immunotherapies or non-immune based strategies in synergistic
      combination. These include targeted therapies such as tyrosine kinase inhibitors,
      co-stimulatory mAbs, bifunctional agents, epigenetic modulators (such as
      inhibitors of histone deacetylases or DNA methyltransferase), vaccines, adoptive
      T-cell therapy, nanoparticles, oncolytic viruses, and even synthetic "gene
      circuits." A number of novel immunotherapy co-targets in pre-clinical development
      are also introduced. The latter include metabolic components, exosomes and ion
      channels. We discuss in some detail of the personalization of immunotherapy
      essential for ultimate maximization of clinical outcomes. Finally, we outline
      possible future technical and conceptual developments including realistic in
      vitro and in vivo models and inputs from physics, engineering, and artificial
      intelligence. We conclude that the breadth and quality of immunotherapeutic
      approaches and the types of cancers that can be treated will increase
      significantly in the foreseeable future.

PMID- 30191145
TI  - The INCLUDE study: INtegrating and improving Care for patients with infLammatory
      rheUmatological DisordErs in the community; identifying multimorbidity: Protocol
      for a pilot randomized controlled trial.
AB  - Background: Patients with inflammatory rheumatic conditions such as rheumatoid
      arthritis, polymyalgia rheumatica and ankylosing spondylitis are at increased
      risk of common comorbidities such as cardiovascular disease, osteoporosis and
      anxiety and depression which lead to increased morbidity and mortality. These
      associated morbidities are often un-recognized and under-treated. While patients
      with other long-term conditions such as diabetes are invited for routine reviews
      in primary care, which may include identification and management of co
      morbidities, at present this does not occur for patients with inflammatory
      conditions, and thus, opportunities to diagnose and optimally manage these
      comorbidities are missed. Objective: To evaluate the feasibility and
      acceptability of a nurse-led integrated care review (the INtegrating and
      improving Care for patients with infLammatory rheUmatological DisordErs in the
      community (INCLUDE) review) for people with inflammatory rheumatological
      conditions in primary care. Design: A pilot cluster randomized controlled trial
      will be undertaken to test the feasibility and acceptability of a nurse-led
      integrated primary care review for identification, assessment and initial
      management of common comorbidities including cardiovascular disease, osteoporosis
      and anxiety and depression. A process evaluation will be undertaken using a mixed
      methods approach including participant self-reported questionnaires, a medical
      record review, an INCLUDE EMIS template, intervention fidelity checking using
      audio-recordings of the INCLUDE review consultation and qualitative interviews
      with patient participants, study nurses and study general practitioners (GPs).
      Discussion: Success of the pilot study will be measured against the engagement,
      recruitment and study retention rates of both general practices and participants.
      Acceptability of the INCLUDE review to patients and practitioners and treatment
      fidelity will be explored using a parallel process evaluation. Trial
      Registration: ISRCTN12765345.

PMID- 30191146
TI  - Treating Pediatric Asthma According Guidelines.
AB  - Asthma is a common chronic inflammatory disorder of the lower respiratory airways
      in childhood. The management of asthma exacerbations and the disease control are
      major concerns for clinical practice. The Global Strategy for Asthma Management
      and Prevention, published by GINA, updated in 2017, the British Thoracic
      Society/Scottish Intercollegiate Guideline Network, revised in 2016, the National
      Institute for Health and Care Excellence asthma guideline consultation, available
      in 2017, are widely accepted documents, frequently implemented, with conflicting
      advices, and different conclusion on asthma definition and treatment. An
      International Consensus on Pediatric Asthma was carried out in 2012 by a
      Committee with expertise in the field, to critically review differences on
      current guidelines. In addition, the specific issue of treating severe and
      difficult asthma has been recently highlighted throughout the International
      European Respiratory Society/American Thoracic Society guidelines on severe
      asthma. The aim of this paper is to describe conventional treatments and some new
      therapeutic approaches to pediatric asthma according to guidelines, highlighting
      key aspects, and differences on proposed clinical recommendations for asthma
      management. Age specific therapy are proposed in steps, according to clinical
      severity and the level of disease control. If control is not achieved within 3
      months, stepping-up should be considered; otherwise, if control is achieved after
      3 months, stepping down may be considered. The most used drug classes of asthma
      medications are beta-2 adrenergic agonists, corticosteroids, and leukotriene
      modifiers. Intramuscolar triamcinolone has been used for severe asthma treatment.
      Chromones and xanthines have been extensively used in the past, but they have
      shown limits related to their efficacy and safety profile. Omalizumab, a
      monoclonal antibody against IgE, is an immunomodulatory biological agent, used as
      new drug in patients with confirmed IgE-mediated allergic asthma, only for
      patient's specific range of total IgE level. There are low evidences in the
      efficacy of metotrexate, as well as macrolide antibiotics in children with
      asthma. Antifungal agents are also not recommended in asthmatic patients. Non
      pharmacological measures that may improve patient's quality of life should also
      be attempted. We conclude that treatment decisions on childhood asthma management
      should be critically made, pondering the differences suggested by agreed
      international consensus documents.

PMID- 30191144
TI  - Protocol for a program of research from the Aging, Community and Health Research
      Unit: Promoting optimal aging at home for older adults with multimorbidity.
AB  - Background: The goal of the Aging, Community and Health Research Unit (ACHRU) is
      to promote optimal aging at home for older adults with multimorbidity (>=2
      chronic conditions) and to support their family/friend caregivers. This protocol
      paper reports the rationale and plan for this patient-oriented, cross
      jurisdictional research program. Objectives: The objectives of the ACHRU research
      program are (i) to codesign integrated and person-centered interventions with
      older adults, family/friend caregivers, and providers; (ii) to examine the
      feasibility of newly designed interventions; (iii) to determine the intervention
      effectiveness on Triple Aim outcomes: health, patient/caregiver experience, and
      cost; (iv) to examine intervention context and implementation barriers and
      facilitators; (v) to use diverse integrated knowledge translation (IKT)
      strategies to engage knowledge users to support scalability and sustainability of
      effective interventions; and (vi) to build patient-oriented research capacity.
      Design: The research program was informed by the Knowledge-to-Action Framework
      and the Complexity Model. Six individual studies were conceptualized as
      integrated pieces of work. The results of the three initial descriptive studies
      will inform and be followed by three pragmatic randomized controlled trials. IKT
      and capacity building activities will be embedded in all six studies and tailored
      to the unique focus of each study. Conclusions: This research program will inform
      the development of effective and scalable person-centered interventions that are
      sustainable through interagency and intersectoral partnerships with community
      based agencies, policy makers, and other health and social service agencies.
      Implementation of these interventions has the potential to transform health-care
      services and systems and improve the quality of life for older adults with
      multimorbidity and their caregivers. Trial registration: NCT02428387 (study 4),
      NCT02158741 (study 5), and NCT02209285 (study 6).

PMID- 30191147
TI  - Nitrogen-Doped Carbon Coated WS2 Nanosheets as Anode for High-Performance Sodium
      Ion Batteries.
AB  - Due to the cost-effectiveness of sodium source, sodium-ion batteries (SIBs) have
      attracted considerable attention. However, SIBs still have some challenges in
      competing with lithium-ion batteries for practical applications. Particularly,
      the high rate capability and cycling stability are posing big problems for SIBs.
      Here, nitrogen-doped carbon-coated WS2 nanosheets (WS2/NC) were successfully
      synthesized by a high-temperature solution method, followed by carbonization of
      polypyrrole. When used as anode electrodes for SIBs, WS2/NC composite exhibited
      high-rate capacity at 386 and 238.1 mAh g-1 at 50 and 2,000 mA g-1, respectively.
      Furthermore, even after 400 cycle, the composite electrode could still deliver a
      capacity of ~180.1 mAh g-1 at 1,000 mA g-1, corresponding to a capacity loss of
      0.09% per cycle. The excellent electrochemical performance could be attributed to
      the synergistic effect of the highly conductive nature of the nitrogen-doped
      carbon-coating and WS2 nanosheets. Results showed that the WS2/NC nanosheets are
      promising electrode materials for SIBs application.

PMID- 30191149
TI  - Extended X-Ray Absorption Fine Structure of ZrW2O8: Theory vs. Experiment.
AB  - Extended x-ray absorption fine structure (EXAFS) is well-suited for
      investigations of structure and disorder of complex materials. Recently,
      experimental measurements and analysis of EXAFS have been carried out to
      elucidate the mechanisms responsible for the negative thermal expansion (NTE) in
      zirconium tungstate (ZrW2O8). In contrast to previous work suggesting that
      transverse O-displacements are largely responsible, the EXAFS analysis suggested
      that correlated rotations and translations of octahedra and tetrahedra within the
      structure are a major source. In an effort to resolve this controversy, we have
      carried out ab initio calculations of the structure, lattice vibrations, and
      EXAFS of ZrW2O8 based on real-space multiple-scattering calculations using the
      FEFF9 code and auxiliary calculations of structure and Debye-Waller factors. We
      find that the theoretical simulations are consistent with observed EXAFS, and
      show that both of the above mechanisms contribute to the dynamical structure of
      ZrW2O8.

PMID- 30191148
TI  - Catalytic and Structural Characterization of a Browning-Related Protein in
      Oriental Sweet Melon (Cucumis Melo var. Makuwa Makino).
AB  - Polyphenol oxidase (PPO) in plants plays an important role in browning reactions
      and may affect the quality of sweet melon products. In this study, a browning
      related protein (BRP) with PPO activity was partially purified from oriental
      sweet melon (Cucumis melo var. makuwa Makino) by salt precipitation and column
      chromatography. The BRP possessed a high degree of identity with several
      chitinase proteins, particularly defense-related proteins, by MS identification.
      Pyrogallol was determined as the most appropriate substrate for BRP (Km = 0.04278
      M). BRP exhibited extreme resistance under alkaline and high temperature
      conditions when pyrogallol was used as substrate. Polyacrylamide gel
      electrophoresis (PAGE) analysis indicated that BRP was a homo-dimer of two
      subunits and had a molecular weight of 37 kDa. Structural analysis indicated that
      the alpha-helix was the dominant conformation of BRP. The active site of the
      protein might be buried deeply in the protein, and BRP might be monodispersed in
      an aqueous system.

PMID- 30191150
TI  - Development of a Metabolite Sensor for High-Throughput Detection of Aldehydes in
      Escherichia Coli.
AB  - We have developed a fluorescence-based metabolite sensor enabling in vivo
      detection of various aldehydes of biotechnological interest in Escherichia coli.
      YqhC is a transcriptional regulator that is known to be involved in the
      upregulation of the yqhD-dgkA operon in the presence of aldehydes. We took
      advantage of this property by constructing a bi-modular biosensor, in which a
      sensing module constitutively expresses yqhC while a reporter module drives the
      expression of the syfp2 reporter gene that is put under control of the yqhD
      promoter. The sensitivity of the sensor has been optimized by engineering the 5'
      UTRs of both the sensing and the reporter modules resulting in a 70-fold gain of
      fluorescence in response to the model compound glycolaldehyde at 5 mM. The
      optimized sensor further responded to other aldehydes when supplemented to the
      cultivation medium at concentrations of 1-10 mM. We furthermore showed that this
      metabolite sensor was functional in vivo as it responded to the presence of
      glycoladehyde that is specifically produced upon induction of a synthetic
      xylulose-1-phosphate pathway expressed in E. coli. This bi-modular sensor can
      therefore be employed as an exquisite tool for FACS-based ultra-high-throughput
      screening of aldehyde (over) producing enzymes.

PMID- 30191151
TI  - Corrigendum: Transcriptomic Profiling of Zebrafish Hair Cells Using RiboTag.
AB  - [This corrects the article DOI: 10.3389/fcell.2018.00047.].

PMID- 30191152
TI  - Two Multicenter Surveys on Equine Back-Pain 10 Years a Part.
AB  - Despite back-pain being a common cause of poor performance in sport horses, a
      tailored diagnostic workflow and a consolidated therapeutic approach are
      currently lacking in equine medicine. The aim of the study was to assess the
      evolution in the veterinarian approach to diagnose and treat back-pain over a 10
      years period. To investigate this topic, two surveys were addressed to equine
      veterinarians working in practice throughout Europe 10 years apart (2006 and
      2016). The answers were organized in an Excel dataset and analyzed. There were 47
      respondents in 2006 and 168 in 2016, from 8 European Countries. The main reasons
      for examining horses with back-pain were poor performance (76%), behavioral
      issues (68%), and lameness (50%). When assessing back pain, 97% of respondents
      applied careful digital pressure over paravertebral muscles, 90% of them used
      digital back mobilization, and 69% was detecting areas of localized heat. The use
      of diagnostic analgesia to confirm the source of pain was rarely employed.
      Radiography and ultrasonography were the most frequent diagnostic imaging
      modalities used to investigate the causes of back-pain in both surveys. Obtaining
      a definitive diagnosis in horses with back-pain is considered challenging due to
      the reduced accessibility of the area and the variability in the pain
      manifestations. Corticosteroids injections were used for local treatments by 80%
      of respondents in 2006 and 92% in 2016. Recently, ultrasonography has been
      extensively used during the injections of the vertebral articular facets and
      sacroiliac joints region. The use of complementary therapies was restricted to a
      low percentage of respondents in the first survey (20%) but it increased over the
      decade. In 2016, a wider percentage of respondents considered osteopathy (40%),
      kinesiotherapy (29%), and acupuncture (22%) when treating back disorders compared
      to 2006. The structural differences of the two surveys did not enable a direct
      data comparison. Based on the results of this surveys, however, veterinarians
      should be sensitized to the back-pain problems and seek to integrate findings
      from clinical research studies in their daily practice.

PMID- 30191154
TI  - Effects of Recovery Mode during High Intensity Interval Training on
      Glucoregulatory Hormones and Glucose Metabolism in Response to Maximal Exercise.
AB  - Catecholamines [adrenaline (A) and noradrenaline (NA)] are known to stimulate
      glucose metabolism at rest and in response to maximal exercise. However, training
      and recovery mode can alter theses hormones. Thus our study aims to examine the
      effects of recovery mode during High-intensity Interval Training (HIIT) on
      glucoregulatory hormone responses to maximal exercise in young adults. Twenty
      four male enrolled in this randomized study, assigned to: control group (eg,
      n=6), and two HIIT groups: intermittent exercise (30 s run/30 s recovery) with
      active (arg, n=9) or passive (prg, n=9) recovery, arg and prg performed HIIT 3
      times weekly for 7 weeks. Before and after HIIT, participants undergo a Maximal
      Graded Test (MGT). Plasma catecholamines, glucose, insulin, growth hormone (Gh)
      and cortisol were determined at rest, at the end of MGT, after 10 and 30 min of
      recovery. After training V02max and Maximal Aerobic Velocity (MAV) increased
      significantly (p<0.05) in arg. After HIIT and in response to MGT plasma glucose
      increase significantly (p=0.008) lesser in arg compared to prg whereas insulin
      concentrations were similar. The glucose/insulin ratio was significantly lower at
      MGT end (p=0.033) only in arg after training. After HIIT, in response to MGT,
      plasma A, NA, cortisol and Gh concentrations were significantly higher only in
      arg (p<0.05). HIIT using active recovery is beneficial for aerobic fitness,
      plasma glucose and glucoregulatory hormones better than HIIT with passive
      recovery. These findings suggest that HIIT with active recovery may improve some
      metabolic and hormonal parameters in young adults.

PMID- 30191153
TI  - Demographic Change Across the Lifespan of Pet Dogs and Their Impact on Health
      Status.
AB  - Although dogs' life expectancies are six to twelve times shorter than that of
      humans, the demographics (e. g., living conditions) of dogs can still change
      considerably with aging, similarly to humans. Despite the fact that the dog is a
      particularly good model for human healthspan, and the number of aged dogs in the
      population is growing in parallel with aged humans, there has been few previous
      attempts to describe demographic changes statistically. We utilized an on-line
      questionnaire to examine the link between the age and health of the dog, and
      owner and dog demographics in a cross-sectional Hungarian sample. Results from
      univariate analyses revealed that 20 of the 27 demographic variables measured
      differed significantly between six dog age groups. Our results revealed that pure
      breed dogs suffered from health problems at a younger age, and may die at an
      earlier age than mixed breeds. The oldest dog group (>12 years) consisted of
      fewer pure breeds than mixed breeds and the mixed breeds sample was on average
      older than the pure breed sample. Old dogs were classified more frequently as
      unhealthy, less often had a "normal" body condition score, and more often
      received medication and supplements. They were also more often male, neutered,
      suffered health problems (such as sensory, joint, and/or tooth problems),
      received less activity/interaction/training with the owner, and were more likely
      to have experienced one or more traumatic events. Surprisingly, the youngest age
      group contained more pure breeds, were more often fed raw meat, and had owners
      aged under 29 years, reflecting new trends among younger owners. The high
      prevalence of dogs that had experienced one or more traumatic events in their
      lifetime (over 40% of the sample), indicates that welfare and health could be
      improved by informing owners of the greatest risk factors of trauma, and
      providing interventions to reduce their impact. Experiencing multiple life events
      such as spending time in a shelter, changing owners, traumatic injury/prolonged
      disease/surgery, getting lost, and changes in family structure increased the
      likelihood that owners reported that their dogs currently show behavioral signs
      that they attribute to the previous trauma.

PMID- 30191155
TI  - Tetracyclines for Treatment of Tularemia: A Case Series.
AB  - Tetracyclines for tularemia have been associated with higher failure rates. There
      were 48 cases of tularemia at the University of Missouri between 1988 and 2015.
      We retrospectively analyzed 17 patients with tularemia who were successfully
      treated with tetracyclines, and 9 of these patients also underwent aspiration or
      incision and drainage.

PMID- 30191156
TI  - An Assessment of Inappropriate Antibiotic Use and Guideline Adherence for
      Uncomplicated Urinary Tract Infections.
AB  - Background: In 2011, The Infectious Diseases Society of America released a
      clinical practice guideline (CPG) that recommended short-course antibiotic
      therapy and avoidance of fluoroquinolones for uncomplicated urinary tract
      infections (UTIs). Recommendations from this CPG were rapidly disseminated to
      clinicians via review articles, UpToDate, and the Centers for Disease Control and
      Prevention website; however, it is unclear if this CPG had an impact on national
      antibiotic prescribing practices. Methods: We performed a retrospective cohort
      study of outpatient and emergency department visits within a commercial insurance
      database between January 1, 2009, and December 31, 2013. We included nonpregnant
      women aged 18-44 years who had an International Classification of Diseases, Ninth
      Revision, Clinical Modification diagnosis code for a UTI with a concurrent
      antibiotic prescription. We performed interrupted time series analyses to
      determine the impact of the CPG on the appropriateness of the antibiotic agent
      and duration. Results: We identified 654 432 women diagnosed with UTI. The
      patient population was young (mean age, 31 years) and had few comorbidities.
      Fluoroquinolones, nonfirstline agents, were the most commonly prescribed
      antibiotic class both before and after release of the guidelines (45% vs 42%).
      Wide variation was observed in the duration of treatment, with >75% of
      prescriptions written for nonrecommended treatment durations. The CPG had minimal
      impact on antibiotic prescribing behavior by providers. Conclusions:
      Inappropriate antibiotic prescribing is common for the treatment of UTIs. The CPG
      was not associated with a clinically meaningful change in national antibiotic
      prescribing practices for UTIs. Further interventions are necessary to improve
      outpatient antibiotic prescribing for UTIs.

PMID- 30191157
TI  - Impact of the 2012 Medicaid Health Care-Acquired Conditions Policy on Catheter
      Associated Urinary Tract Infection and Vascular Catheter-Associated Infection
      Billing Rates.
AB  - In July 2012, the Centers for Medicare & Medicaid Services ceased hospital
      Medicaid reimbursements for certain health care-acquired conditions. Using
      billing data from 2008-2014, we found no impact of this policy on rates of 2
      targeted conditions, vascular catheter-associated infections and catheter
      associated urinary tract infections, among Medicaid or non-Medicaid patients.

PMID- 30191158
TI  - High Prevalence of Late-Stage Disease in Newly Diagnosed Human Immunodeficiency
      Virus Patients in Sierra Leone.
AB  - A high prevalence of late-stage disease (75.4%) and severe immunosuppression
      (23.3%) was observed in 155 newly diagnosed human immunodeficiency virus patients
      in Freetown, Sierra Leone during August to November 2017. Within the late-stage
      diagnosis group, a significantly high proportion of patients reported fever
      (84.2% vs 65.2%; P = .01), weight loss (82.2% vs 63.5%; P = .01), and malaise
      (89.7% vs 71.7%; P = .05). Fever was identified as the only independent predictor
      of late-stage disease in this study.

PMID- 30191159
TI  - Targeting Root Cause by Systemic scAAV9-hIDS Gene Delivery: Functional Correction
      and Reversal of Severe MPS II in Mice.
AB  - No treatment is available to address the neurological need and reversibility of
      MPS II. We developed a scAAV9-hIDS vector to deliver the human iduronate-2
      sulfatase gene and test it in mouse model. We treated MPS II mice at different
      disease stages with an intravenous injection of scAAV9-mCMV-hIDS at different
      doses. The treatments led to rapid and persistent restoration of IDS activity and
      the reduction of glycosaminoglycans (GAG) throughout the CNS and somatic tissues
      in all cohorts. Importantly, the vector treatment at up to age 6 months improved
      behavior performance in the Morris water maze and normalized the survival.
      Notably, vector treatment at age 9 months also resulted in persistent rIDS
      expression and GAG clearance in MPS II mice, and the majority of these animals
      survived within the normal range of lifespan. Notably, the vector delivery did
      not result in any observable adverse events or detectable systemic toxicity in
      any treated animal groups. We believe that we have developed a safe and effective
      gene therapy for treating MPS II, which led to recent IND approval for a phase
      1/2 clinical trial in MPS II patients, further supporting the extended potential
      of the demonstrated systemic rAAV9 gene delivery platform for broad disease
      targets.

PMID- 30191160
TI  - A Nontoxic Transduction Enhancer Enables Highly Efficient Lentiviral Transduction
      of Primary Murine T Cells and Hematopoietic Stem Cells.
AB  - Lentiviral vectors have emerged as an efficient, safe therapeutic tool for gene
      therapy based on hematopoietic stem cells (HSCs) or T cells. However, the
      monitoring of transduced cells in preclinical models remains challenging because
      of the inefficient transduction of murine primary T cells with lentiviral
      vectors, in contrast to gammaretroviral vectors. The use of this later in
      preclinical proof of concept is not considered as relevant when a lentiviral
      vector will be used in a clinical trial. Hence, there is an urgent need to
      develop an efficient transduction protocol for murine cells with lentiviral
      vectors. Here, we describe an optimized protocol in which a nontoxic transduction
      enhancer (Lentiboost) enables the efficient transduction of primary murine T
      cells with lentiviral vectors. The optimized protocol combines low toxicity and
      high transduction efficiency. We achieved a high-level transduction of murine
      CD4+ and CD8+ T cells with a VSV-G-pseudotyped lentiviral vector with no changes
      in the phenotypes of transduced T cells, which were stable and long-lived in
      culture. This enhancer also increased the transduction of murine HSCs. Hence, use
      of this new transduction enhancer overcomes the limitations of lentiviral vectors
      in preclinical experiments and should facilitate the translation of strategies
      based on lentiviral vectors from the bench to the clinic.

PMID- 30191162
TI  - Knife wielding radiologist: A case report of primary pancreatic lymphoma.
AB  - Majority of malignant pancreatic neoplasms are epithelial in origin and mostly
      arise from exocrine gland. Ductal adenocarcinoma compromises the major
      histological type of such tumors. Primary non-epithelial tumors of exocrine
      pancreatic gland are extremely rare and incorporate lymphoma and sarcoma. Primary
      pancreatic lymphoma compromises less than 0.5% of pancreatic malignancies.
      Primary pancreatic lymphoma can be difficult to differentiate from pancreatic
      adenocarcinoma and other neoplasms on imaging, and a correct diagnosis is crucial
      for appropriate patient management.

PMID- 30191161
TI  - Osseointegration of Coarse and Fine Textured Implants Manufactured by Electron
      Beam Melting and Direct Metal Laser Sintering.
AB  - Osseointegrated implants transfer loads from native bone to a synthetic joint and
      can also function transdermally to provide a stable connection between the
      skeleton and the prostheses, eliminating many problems associated with socket
      prostheses. Additive manufacturing provides a cost-effective means to create
      patient-specific implants and allows for customized textures for integration with
      bone and other tissues. Our objective was to compare the osseointegration
      strength of two primary additive manufacturing methods of producing textured
      implants: electron beam melting (EBM) (mean Ra = 23 MUm) and direct metal laser
      sintering (DMLS) (mean Ra = 10 MUm). Due to spatial resolution, DMLS can produce
      surfaces with a roughness comparable to EBM. Two cohorts of Sprague-Dawley rats
      received bilateral, titanium implants in their distal femurs and were followed
      for 4 weeks. The first-cohort animals received EBM implants transcortically in
      one femur and a DMLS implant in the contralateral femur. The second cohort
      received DMLS implants (either fine textured or coarse textured to mimic EBM) in
      the intramedullary canal of each femur. Osseointegration was evaluated through
      mechanical testing and micro-computed tomography (bone volume fraction [BV/TV]
      and bone-implant contact [BIC]). The fixation strength of coarse textured
      implants provided superior interlocking relative to fine textured implants
      without affecting BV/TV or BIC in both cohorts. Coarse EBM implants in a
      transcortical model demonstrated an 85% increase in removal torque relative to
      the fine DMLS textured implants. The thrust load in the intramedullary model saw
      a 35% increase from fine to coarse DMLS implants.

PMID- 30191163
TI  - Pleural thymoma: Radiological and histological findings.

PMID- 30191165
TI  - Data on the effects of cellulase hydrolysis, acid treatment and particle size
      distribution on physicochemical and functional properties of coconut (cocos
      nucifera L) cake dietary fibres.
AB  - The data presented in this article are related to the research article entitled
      "Physicochemical and functional properties of coconut (Cocos nucifera L) cake
      dietary fibres: Effects of cellulase hydrolysis, acid treatment and particle size
      distribution" [1]. This article describes the effect of acidic treatment,
      cellulase hydrolysis and particle size distribution on the monosaccharide
      composition, X-ray diffraction, Fourier-transformed infrared and spectroscopy
      surface area of coconut cake dietary fiber. The field data set is made publicly
      available to the potential re-use of coconut cake or other plants by-products.

PMID- 30191164
TI  - Phosphoproteome data from abscisic acid and ethylene treated Glycine max leaves.
AB  - The data reported here are associated with the article "Comparative
      phosphoproteome analysis upon ethylene and abscisic acid treatment in Glycine max
      leaves" [1]. Phosphorylation plays a critical role in the regulation of the
      biological activities of proteins. However, phosphorylation-mediated regulation
      of proteins and pathways involved in ethylene (ET) and abscisic acid (ABA)
      signaling is currently poorly understood. Therefore, we used a shotgun proteomics
      approach to identify the phosphopeptides and phosphoproteins in response to ET,
      ABA and combined ET+ABA treatments. Here, we present the Mass spectrometry,
      protein-protein interaction, Gene ontology and KEGG data associated with the ET
      and ABA signaling in soybean leaves [1].

PMID- 30191166
TI  - Data on genome annotation and analysis of earthworm Eisenia fetida.
AB  - The present article reports the complete draft genome annotation of earthworm
      Eisenia fetida, obtained from the manuscript entitled "Timing and Scope of
      Genomic Expansion within Annelida: Evidence from Homeoboxes in the Genome of the
      Earthworm E. fetida" (Zwarycz et al., 2015) and provides the data on the
      repetitive elements, protein coding genes and noncoding RNAs present in the
      genome dataset of the species. The E. fetida protein coding genes were predicted
      from AUGUSTUS gene prediction and subsequently annotated based on their sequence
      similarity, Gene Ontology (GO) functional terms, InterPro domains, Clusters of
      Orthologous Groups (COGs) and KEGG (Kyoto Encyclopedia of Genes and Genomes)
      pathways information. The genome wide comparison of orthologous clusters and
      phylogenomic analysis of the core genes were performed to understand the events
      of genome evolution and genomic diversity between E. fetida and its related
      metazoans. In addition, the genome dataset was screened to identify the crucial
      stem cell markers, regeneration specific genes and immune-related genes and their
      functionally enriched GO terms were predicted from Fisher's enrichment analysis.
      The E. fetida genome annotation data containing the GFF (general feature format)
      annotation file, predicted coding gene sequences and translated protein sequences
      were deposited to the figshare repository under the DOI:
      https://doi.org/10.6084/m9.figshare.6142322.v1.

PMID- 30191167
TI  - Dataset on SPT-based seismic soil liquefaction.
AB  - This data article provides a summary of seismic soil liquefaction triggering and
      non-triggering case histories, which were compiled, screened for data
      completeness and quality, and then processed for the development of triggering
      relationships proposed in "SPT-based probabilistic and deterministic assessment
      of seismic soil liquefaction triggering hazard" [1]. The database is composed of
      113 liquefaction, 95 non-liquefaction, and 2 marginal liquefaction case
      histories, from seismic events with moment magnitude Mw values varying in the
      range of 5.9 to 8.3. A spreadsheet summary of these case histories are included
      along with a separate spreadsheet, by which maximum likelihood assessment was
      performed. These data transparently enable researchers to access case history
      input parameters and processing details, and to compare the case history
      processing protocols with the ones of different researchers (e.g.: "The influence
      of SPT procedures in soil liquefaction resistance evaluations." [2], "SPT-based
      liquefaction triggering procedures." [3]).

PMID- 30191168
TI  - Data on how students' involvement with ENACTUS can affect their decision for
      entrepreneurship.
AB  - The data are descriptions of the responses of the students that attended the
      ENACTUS (ENtrepreneurial ACTion US) Nigeria leadership conference 2018, which
      held from February 19 to 21, 2018. Hence, this data article describes the age
      range of the students, the amount of ENACTUS projects they have been involved in,
      their willingness to start their ventures, when they would like to launch their
      ventures and the industries they would like to venture into. The Google Doc
      Online Form was used to design the questionnaire used for sourcing the data. 109
      respondents, of 333 that attended the conference, completed the questionnaire.

PMID- 30191169
TI  - Data for estimating the U.S. labor wedge.
AB  - The after-tax labor wedge is defined as the log difference between the MRS and
      the MPL excluding taxes. This article introduces the data and approach that are
      used to estimate the U.S. after-tax labor wedge to provide empirical support for
      the research article entitled "Credit Crunch, Heterogeneity and the Labor Wedge"
      (Zhang, 2018 (Forthcoming)) [4]. I measure the U.S. after-tax labor wedge and
      then decompose it into the sum of the gap between the MPL and the real wage (the
      MPL component) and the gap between the real wage and the MRS (the MRS component).
      The after-tax labor wedge and its decomposition are measured using quarterly data
      from 1947Q1 to 2017Q3.

PMID- 30191170
TI  - Data on the inhibitory effect of traditional plants from Sri Lanka against
      tyrosinase and collagenase.
AB  - This article describes the inhibitory effects of extracts from 25 plants
      harvested in Sri Lanka against tyrosinase and collagenase. Inhibitors of these
      enzymes are common ingredients in cosmetics and medications, which help protect
      the skin against hyperpigmentation and premature aging. The article also
      discusses the polyphenol content of the extracts, which is well known to possess
      antioxidant properties. The extract data from the following plants, which have a
      long history in Sri Lankan traditional medicine, such as Ayurveda, have been
      provided: English name, "local name in Sri Lanka," (scientific name). Indian
      copperleaf plant, "kuppameniya," (Acalypha indica); red sandalwood, "madatiya",
      (Adenanthera pavonina); balipoovu plant, "polpala," (Aerva lanata); snap ginger,
      "heen araththa," (Alpinia calcarata); bael fruit, "beli," (Aegle marmelos);
      coastal waterhyssop, "lunuwila," (Bacopa monnieri); porcupine flower, "katu
      karandu," (Barleria prionitis); balloon-vine plant, "wel penera," (Cardiospermum
      halicacabum); water caltrop, "Katupila," (Flueggea leucopyrus); Indian
      sarsparilla, "iramusu," (Hemidesmus indicus); malabar nut plant, "adhatoda,"
      (Justicia adhatoda); wood apple, "divul," (Limonia acidissima); holy basil plant,
      "maduruthala," (Ocimum tenuiflorum); emblic myrobalan plant, "nelli,"
      (Phyllanthus emblica); long pepper plant,"thippili," (Piper longum); country
      borage plant, "kapparawalliya," (Plectranthus amboinicus); common sesban, "wel
      murunga," (Sesbania sesban); turkey berry, "gona batu," (Solanum rudepannum
      Dunal); purple fruited pea eggplant,"welthibbatu," (Solanum trilobatum); black
      plum, "madan," (Syzygium cumini); crape jasmine, "wathusudda," (Tabernaemontana
      divaricate); purple tephrosia, "pila," (Tephrosia purpurea); Chinese chaste tree,
      "nika," (Vitex negundo); and arctic snow, "suduidda," (Wrightia antidysenterica).
      The inhibitory effects of these plant extracts on tyrosinase and collagenase, as
      well as polyphenol contents in the extracts, are detailed in Table 1.

PMID- 30191171
TI  - Data on photo-catalytic degradation of 4- chlorophenol from aqueous solution
      using UV/ZnO/persulfate.
AB  - The presence of chlorinated aromatic pollutants like 4- chlorophenol (4CP), even
      at low concentrations, in the wastewater should be controlled urgently, because
      of their high toxicity, carcinogenic potential and poor biodegradability. This
      dataset reveals the effectiveness of an advanced oxidation process (AOP) for
      attenuating of 4 CP. The AOP of UV/ZnO/persulfate and the influence of various
      parameters like pH, persulfate dosage and ZnO dosage were studied and the optimum
      removal conditions could be easily implied by readerships. The efficiency of >
      90% was attained for degrading of 4CP by UV/ZnO/persulfate system at the
      experimental conditions of pH of 7, persulfate dosage of 11 mg/L, 4CP
      concentration of 10 mg/L, and ZnO dosage of 1 g/L. The data had a good agreement
      with pseudo first-order kinetic model. Thus, the UV/ZnO/persulfate system is an
      efficient method for decreasing 4CP from aqueous solution.

PMID- 30191173
TI  - The second century CE Roman watermills of Barbegal: Unraveling the enigma of one
      of the oldest industrial complexes.
AB  - The second century CE Roman watermill complex of Barbegal, France, is regarded as
      one of the first industrial complexes in human history. The 16 water wheels are
      no longer extant as all woodwork has decayed. However, carbonate deposits
      precipitated from water during operation of the mills forming casts on the
      woodwork. These casts are preserved in fragments and provide unique insights into
      the frequency of use and maintenance of the mills, and even into the structure of
      the water wheel chambers. Stable isotope time series of carbonate deposits reveal
      that the mill activity was regularly interrupted for several months. This
      strongly suggests that the mill complex was not used for a steady supply of flour
      to a major population center, as previously thought, but likely served to produce
      nonperishable hardtack for the nearby harbors.

PMID- 30191172
TI  - Ancient genome-wide analyses infer kinship structure in an Early Medieval
      Alemannic graveyard.
AB  - From historical and archeological records, it is posited that the European
      medieval household was a combination of close relatives and recruits. However,
      this kinship structure has not yet been directly tested at a genomic level on
      medieval burials. The early 7th century CE burial at Niederstotzingen, discovered
      in 1962, is the most complete and richest example of Alemannic funerary practice
      in Germany. Excavations found 13 individuals who were buried with an array of
      inscribed bridle gear, jewelry, armor, and swords. These artifacts support the
      view that the individuals had contact with France, northern Italy, and Byzantium.
      This study analyzed genome-wide sequences recovered from the remains, in tandem
      with analysis of the archeological context, to reconstruct kinship and the extent
      of outside contact. Eleven individuals had sufficient DNA preservation to
      genetically sex them as male and identify nine unique mitochondrial haplotypes
      and two distinct Y chromosome lineages. Genome-wide analyses were performed on
      eight individuals to estimate genetic affiliation to modern west Eurasians and
      genetic kinship at the burial. Five individuals were direct relatives. Three
      other individuals were not detectably related; two of these showed genomic
      affinity to southern Europeans. The genetic makeup of the individuals shares no
      observable pattern with their orientation in the burial or the cultural
      association of their grave goods, with the five related individuals buried with
      grave goods associated with three diverse cultural origins. These findings
      support the idea that not only were kinship and fellowship held in equal regard:
      Diverse cultural appropriation was practiced among closely related individuals as
      well.

PMID- 30191174
TI  - Transcranial brain atlas.
AB  - We introduce here the concept of a transcranial brain atlas (TBA), a new kind of
      brain atlas specialized for transcranial techniques. A TBA is a probabilistic
      mapping from scalp space to atlas label space, relating scalp locations to
      anatomical, functional, network, genetic, or other labels. TBAs offer a new way
      to integrate and present structural and functional organization of the brain and
      allow previously subsurface and invisible atlas labels visible on the scalp
      surface to accurately guide the placement of transcranial devices directly on the
      scalp surface in a straightforward, visual manner. We present here a framework
      for building TBAs that includes (i) a new, continuous proportional coordinate
      system devised for the scalp surface to allow standardized specification of scalp
      positions; (ii) a high-resolution, large sample-based (114-participant) mapping
      from scalp space to brain space to accurately and reliably describe human cranio
      cortical correspondence; and (iii) a two-step Markov chain to combine the
      probabilistic scalp-brain mapping with a traditional brain atlas, bringing atlas
      labels to the scalp surface. We assessed the reproducibility (consistency of TBAs
      generated from different groups) and predictiveness (prediction accuracy of
      labels for individuals without brain images) of the TBAs built via our framework.
      Moreover, we present an application of TBAs to a functional near-infrared
      spectroscopy finger-tapping experiment, illustrating the utility and benefits of
      TBAs in transcranial studies. Our results demonstrate that TBAs can support
      ongoing efforts to map the human brain using transcranial techniques, just as
      traditional brain atlases have supported magnetic resonance imaging and positron
      emission tomography studies.

PMID- 30191177
TI  - Middle-Late Triassic insect radiation revealed by diverse fossils and isotopic
      ages from China.
AB  - The Triassic represented an important period that witnessed the diversification
      of marine and terrestrial ecosystems. The radiations of terrestrial plants and
      vertebrates during this period have been widely investigated; however, the
      Triassic history of insects, the most diverse group of organisms on Earth,
      remains enigmatic because of the rarity of Early-Middle Triassic fossils. We
      report new insect fossils from a Ladinian deposit (Tongchuan entomofauna) dated
      to approximately 238 to 237 million years ago and a Carnian deposit (Karamay
      entomofauna) in northwestern China, including the earliest definite caddisfly
      cases (Trichoptera), water boatmen (Hemiptera), diverse polyphagan beetles
      (Coleoptera), and scorpionflies (Mecoptera). The Tongchuan entomofauna is near
      the Ladinian-Carnian boundary in age, providing a calibration date for
      correlation to contemporaneous biotas. Our findings confirm that the clade
      Holometabola, comprising most of the modern-day insect species, experienced
      extraordinary diversification in the Middle-Late Triassic. Moreover, our results
      suggest that the diversification of aquatic insects (a key event of the "Mesozoic
      Lacustrine Revolution") had already begun by the Middle Triassic, providing new
      insights into the early evolution of freshwater ecosystems.

PMID- 30191175
TI  - PGE2 production at sites of tissue injury promotes an anti-inflammatory
      neutrophil phenotype and determines the outcome of inflammation resolution in
      vivo.
AB  - Neutrophils are the first immune cells recruited to a site of injury or
      infection, where they perform many functions. Having completed their role,
      neutrophils must be removed from the inflammatory site-either by apoptosis and
      efferocytosis or by reverse migration away from the wound-for restoration of
      normal tissue homeostasis. Disruption of these tightly controlled physiological
      processes of neutrophil removal can lead to a range of inflammatory diseases. We
      used an in vivo zebrafish model to understand the role of lipid mediator
      production in neutrophil removal. Following tailfin amputation in the absence of
      macrophages, neutrophillic inflammation does not resolve, due to loss of
      macrophage-dependent handling of eicosanoid prostaglandin E2 (PGE2) that drives
      neutrophil removal via promotion of reverse migration. Knockdown of endogenous
      PGE synthase gene reveals PGE2 as essential for neutrophil inflammation
      resolution. Furthermore, PGE2 is able to signal through EP4 receptors during
      injury, causing an increase in Alox12 production and switching toward anti
      inflammatory eicosanoid signaling. Our data confirm regulation of neutrophil
      migration by PGE2 and LXA4 (lipoxin A4) in an in vivo model of inflammation
      resolution. This pathway may contain therapeutic targets for driving inflammation
      resolution in chronic inflammatory disease.

PMID- 30191179
TI  - Little lasting impact of the Paleocene-Eocene Thermal Maximum on shallow marine
      molluscan faunas.
AB  - Global warming, acidification, and oxygen stress at the Paleocene-Eocene Thermal
      Maximum (PETM) are associated with severe extinction in the deep sea and major
      biogeographic and ecologic changes in planktonic and terrestrial ecosystems, yet
      impacts on shallow marine macrofaunas are obscured by the incompleteness of shelf
      sections. We analyze mollusk assemblages bracketing (but not including) the PETM
      and find few notable lasting impacts on diversity, turnover, functional ecology,
      body size, or life history of important clades. Infaunal and chemosymbiotic taxa
      become more common, and body size and abundance drop in one clade, consistent
      with hypoxia-driven selection, but within-clade changes are not generalizable
      across taxa. While an unrecorded transient response is still possible, the long
      term evolutionary impact is minimal. Adaptation to already-warm conditions and
      slow release of CO2 relative to the time scale of ocean mixing likely buffered
      the impact of PETM climate change on shelf faunas.

PMID- 30191176
TI  - Transparent arrays of bilayer-nanomesh microelectrodes for simultaneous
      electrophysiology and two-photon imaging in the brain.
AB  - Transparent microelectrode arrays have emerged as increasingly important tools
      for neuroscience by allowing simultaneous coupling of big and time-resolved
      electrophysiology data with optically measured, spatially and type resolved
      single neuron activity. Scaling down transparent electrodes to the length scale
      of a single neuron is challenging since conventional transparent conductors are
      limited by their capacitive electrode/electrolyte interface. In this study, we
      establish transparent microelectrode arrays with high performance, great
      biocompatibility, and comprehensive in vivo validations from a recently
      developed, bilayer-nanomesh material composite, where a metal layer and a low
      impedance faradaic interfacial layer are stacked reliably together in a same
      transparent nanomesh pattern. Specifically, flexible arrays from 32 bilayer
      nanomesh microelectrodes demonstrated near-unity yield with high uniformity,
      excellent biocompatibility, and great compatibility with state-of-the-art
      wireless recording and real-time artifact rejection system. The electrodes are
      highly scalable, with 130 kilohms at 1 kHz at 20 MUm in diameter, comparable to
      the performance of microelectrodes in nontransparent Michigan arrays. The highly
      transparent, bilayer-nanomesh microelectrode arrays allowed in vivo two-photon
      imaging of single neurons in layer 2/3 of the visual cortex of awake mice, along
      with high-fidelity, simultaneous electrical recordings of visual-evoked activity,
      both in the multi-unit activity band and at lower frequencies by measuring the
      visual-evoked potential in the time domain. Together, these advances reveal the
      great potential of transparent arrays from bilayer-nanomesh microelectrodes for a
      broad range of utility in neuroscience and medical practices.

PMID- 30191178
TI  - Leg force interference in polypedal locomotion.
AB  - The examination of gaits and gait changes has been the focus of movement
      physiology and legged robot engineering since the first emergence of the fields.
      While most examinations have focused on bipedal and quadrupedal designs, many
      robotic implementations rely on the higher static stability of three or more
      pairs of legs. Thus far, however, the effect of number of pairs of legs on
      locomotion dynamics has not been examined. Accordingly, the present approach aims
      to extend available theory to polypedal designs and examines how the number of
      active walking legs affects body dynamics when combined with changing duty
      factors and phase relations. The model shows that ground force interference of
      higher numbers of active pairs of walking legs can prevent effective use of
      bouncing gaits, such as trot, and their associated advantages, such as energy
      efficiency, because significantly higher degrees of leg synchronization are
      required. It also shows that small changes in the leg coordination pattern have a
      much higher impact on the center-of-mass dynamics in locomotor systems with many
      legs than in those with fewer legs. In this way, the model reveals coordinative
      constraints for specific gaits facilitating the assessment of animal locomotion
      and economization of robotic locomotion.

PMID- 30191181
TI  - Metabolic Activity of Sulfate-Reducing Bacteria from Rodents with Colitis.
AB  - Sulfate-reducing bacteria (SRB) are anaerobic microorganisms, which use sulfate
      as an electron acceptor in the process of dissimilatory sulfate reduction. The
      final metabolic product of these anaerobic microorganisms is hydrogen sulfide,
      which is known as toxic and can lead to damage to epithelial cells of the large
      intestine at high concentrations. Different genera of SRB are detected in the
      large intestine of healthy human and animals, and with diseases like Crohn's
      disease and ulcerative colitis. SRB isolated from rodents with ulcerative colitis
      have produced 1.14 (mice) and 1.03 (rats) times more sulfide ions than healthy
      rodents. The species of Desulfovibrio genus are the most widespread among all SRB
      in the intestine. The object of our research was to observe and compare the
      difference of production of sulfide and reduction of sulfate in intestinal SRB
      isolated from healthy rodents and rodents with ulcerative colitis.

PMID- 30191180
TI  - Accelerated ex situ breeding of GBSS- and PTST1-edited cassava for modified
      starch.
AB  - Crop diversification required to meet demands for food security and industrial
      use is often challenged by breeding time and amenability of varieties to genome
      modification. Cassava is one such crop. Grown for its large starch-rich storage
      roots, it serves as a staple food and a commodity in the multibillion-dollar
      starch industry. Starch is composed of the glucose polymers amylopectin and
      amylose, with the latter strongly influencing the physicochemical properties of
      starch during cooking and processing. We demonstrate that CRISPR-Cas9 (clustered
      regularly interspaced short palindromic repeats/CRISPR-associated protein 9)
      mediated targeted mutagenesis of two genes involved in amylose biosynthesis,
      PROTEIN TARGETING TO STARCH (PTST1) or GRANULE BOUND STARCH SYNTHASE (GBSS), can
      reduce or eliminate amylose content in root starch. Integration of the
      Arabidopsis FLOWERING LOCUS T gene in the genome-editing cassette allowed us to
      accelerate flowering-an event seldom seen under glasshouse conditions. Germinated
      seeds yielded S1, a transgene-free progeny that inherited edited genes. This
      attractive new plant breeding technique for modified cassava could be extended to
      other crops to provide a suite of novel varieties with useful traits for food and
      industrial applications.

PMID- 30191182
TI  - Balancing science and political economy: Tobacco control and global health.
AB  - Background: Global tobacco control is a major public health issue, as smoking
      related disease burden remains high worldwide. The World Bank and the World
      Health Organization (WHO) are the driving forces in global tobacco control.
      However, little research has focused on their development, financing, decision
      making, and accountability structures. Methods: We used two strategies to
      identify the development and structure of global tobacco control initiatives.
      First, we reviewed the published literature through electronic databases. Second,
      we conducted grey literature searching. Results: We identified four periods in
      the Bank's involvement in global tobacco control, from creation of the evidence
      base in the 1990s to the implementation of tax reforms. We identified three
      phases in the WHO's efforts, from its early recognition of the link between
      tobacco and health risks in the 1970s to its implementation of the Framework
      Convention on Tobacco Control. Both organisations are financed by a handful of
      private philanthropies, and face similar risks for effective tobacco control:
      reduced accountability and resource mobilisation, poor decision-making authority
      due to specific donor influence, and difficulty in monitoring and evaluation.
      Conclusions: Continued attention should be paid not only to the primary health
      related outcomes of tobacco use, but also to the decision-making and financing
      structures to promote tobacco control activities.

PMID- 30191185
TI  - Design, synthesis and evaluation of novel 2,2-dimethyl-2,3-dihydroquinolin-4(1H)
      one based chalcones as cytotoxic agents.
AB  - We designed and synthesised a series of novel chalcones, incorporating the
      heterocyclic framework of 2,2-dimethyl-2,3-dihydro-4(1H)-quinolinone, which was
      prepared via Sonogashira coupling of a substituted orthoaniline under aqueous
      conditions using Pd catalysis followed by acid-mediated cyclisation. The
      compounds were screened against the NCI-N87 and DLD-1 cancer cell lines, with
      most compounds showing low micromolar cytotoxic activity.

PMID- 30191184
TI  - Reaching a consensus on research priorities for supporting women with autoimmune
      rheumatic diseases during pre-conception, pregnancy and early parenting: A
      Nominal Group Technique exercise with lay and professional stakeholders.
AB  - Background:Women with autoimmune rheumatic diseases (ARDs) find it difficult to
      get information and support with family planning, pregnancy, and early parenting.
      A systematic approach to prioritising research is required to accelerate
      development and evaluation of interventions to meet the complex needs of this
      population.  Methods:A Nominal Group Technique (NGT) exercise was carried out
      with lay and professional stakeholders (n=29). Stakeholders were prepared for
      debate through presentation of available evidence. Stakeholders completed three
      tasks to develop, individually rank, and reach consensus on research priorities:
      Task 1 - mapping challenges and services using visual timelines; Task 2 -
      identifying research topics; Task 3 - individually ranking research topics in
      priority order. Results of the ranking exercise were fed back to the group for
      comment.   Results:The main themes emerging from Task 1 were the need for
      provision of information, multi-disciplinary care, and social and peer support.
      In Task 2, 15 research topics and 58 sub-topics were identified around addressing
      the challenges and gaps in care identified during Task 1.  In Task 3, a consensus
      was reached on the ten research topics that should be given the highest priority.
      These were individually ranked, resulting in the following order of priorities
      (from 1 - highest to 10 - lowest): 1. Shared decision-making early in the care
      pathway; 2. Pre-conception counseling; 3. Information about medication use during
      pregnancy/breastfeeding; 4. Personalised care planning; 5. Support for
      partners/family members; 6. Information about local support/disease specific
      issues; 7. Shared decision-making across the care pathway; 8. Peer-support; 9.
      Social inequalities in care, and; 10. Guidance on holistic/alternative therapies.
      Conclusions:This systematic approach to identification of research priorities
      from a multi-disciplinary and lay perspective indicated that activities should
      focus on development and evaluation of interventions that increase patient
      involvement in clinical decision-making, multi-disciplinary models of care, and
      timely provision of information.

PMID- 30191183
TI  - Pulmonary epithelial barrier and immunological functions at birth and in early
      life - key determinants of the development of asthma?  A description of the
      protocol for the Breathing Together study.
AB  - Background.  Childhood asthma is a common complex condition whose aetiology is
      thought to involve gene-environment interactions in early life occurring at the
      airway epithelium, associated with immune dysmaturation.  It is not clear if
      abnormal airway epithelium cell (AEC) and cellular immune system functions
      associated with asthma are primary or secondary.  To explore this, we will (i)
      recruit a birth cohort and observe the evolution of respiratory symptoms; (ii)
      recruit children with and without asthma symptoms; and (iii) use existing data
      from children in established STELAR birth cohorts.    Novel pathways identified
      in the birth cohort will be sought in the children with established disease.  Our
      over-arching hypothesis is that epithelium function is abnormal at birth in
      babies who subsequently develop asthma and progression is driven by abnormal
      interactions between the epithelium, genetic factors, the developing immune
      system, and the microbiome in the first years of life. Methods.  One thousand
      babies will be recruited and nasal AEC collected at 5-10 days after birth for
      culture.  Transcriptomes in AEC and blood leukocytes and the upper airway
      microbiome will be determined in babies and again at one and three years of age.
      In a subset of 100 individuals, AEC transcriptomes and microbiomes will also be
      assessed at three and six months.  Individuals will be assigned a wheeze category
      at age three years.  In a cross sectional study, 300 asthmatic and healthy
      children aged 1 to 16 years will have nasal and bronchial AEC collected for
      culture and transcriptome analysis, leukocyte transcriptome analysis, and upper
      and lower airway microbiomes ascertained.  Genetic variants associated with
      asthma symptoms will be confirmed in the STELAR cohorts.  Conclusions.  This
      study is the first to comprehensively study the temporal relationship between
      aberrant AEC and immune cell function and asthma symptoms in the context of early
      gene-microbiome interactions.

PMID- 30191186
TI  - User's guide to correlation coefficients.
AB  - When writing a manuscript, we often use words such as perfect, strong, good or
      weak to name the strength of the relationship between variables. However, it is
      unclear where a good relationship turns into a strong one. The same strength of r
      is named differently by several researchers. Therefore, there is an absolute
      necessity to explicitly report the strength and direction of r while reporting
      correlation coefficients in manuscripts. This article aims to familiarize medical
      readers with several different correlation coefficients reported in medical
      manuscripts, clarify confounding aspects and summarize the naming practices for
      the strength of correlation coefficients.

PMID- 30191187
TI  - Acute coronary syndromes diagnosis, version 2.0: Tomorrow's approach to
      diagnosing acute coronary syndromes?
AB  - Chest pain accounts for approximately 6% of Emergency Department (ED) attendances
      and is the most common reason for emergency hospital admission. For many years,
      our approach to diagnosis has required patients to stay in hospital for at least
      6-12 h to undergo serial biomarker testing. As less than one fifth of the
      patients undergoing investigation actually has an acute coronary syndrome (ACS),
      there is tremendous potential to reduce unnecessary hospital admissions. Recent
      advances in diagnostic technology have improved the efficiency of care pathways.
      Decision aids such as the Thrombolysis in Myocardial Infarction (TIMI) risk score
      and the History, Electrocardiogram, Age, Risk factors and Troponin (HEART) score
      enable rapid 'rule out' of ACS within hours of patients arriving in the ED. With
      high sensitivity cardiac troponin (hs-cTn) assays, approximately one third of
      patients can have ACS 'ruled out' with a single blood test, and up to two thirds
      could have an acute myocardial infarction 'ruled out' with a second sample taken
      after as little as 1 h. Building on those recent advances, this paper presents an
      overview of the principles behind the development of the Troponin-only Manchester
      Acute Coronary Syndromes (T-MACS) decision aid. This clinical prediction model
      could be used to 'rule out' and 'rule in' ACS following a single blood test and
      to calculate the probability of ACS for every patient. The future potential of
      this approach is then addressed, including practical applications of artificial
      intelligence, shared decision making, near-patient testing and personalized
      medicine.

PMID- 30191188
TI  - Assessment of EFAST training for final year medical students in emergency
      medicine clerkship.
AB  - Background: Extended Focused Assessment Sonography for Trauma (EFAST) is an
      important bedside tool for the management of multiple trauma patients. We aimed
      to evaluate the assessment of our EFAST education in the Emergency Medicine
      Clerkship (EMC) for final year medical students and the correlations of EFAST
      marks with other practical skill stations and the final multiple choice question
      (MCQ) exam marks. Methods: Fifty-four final year medical students were trained on
      performing EFAST on human models during their 4-week clerkship. Students received
      an hour of didactic lecture, 4-hours practical sessions on human models, and
      completed a minimum of three EFAST examinations on trauma patients. Finally, the
      EFAST performance was evaluated on human models using a standard evaluation form
      during an Objective Structured Clinical Examination (OSCE). The marks of 51
      students who completed the final exam were analyzed. Results: The overall passing
      rate of the EFAST station was 88% (n: 45). EFAST station mark had significant
      weak correlations with other OSCE stations marks (p = 0.027, rho = 0.31), and
      with the final EMC mark (p = 0.032, rho = 0.3), but not with the final MCQ exam.
      Conclusions: Final year medical students demonstrated effective EFAST learning as
      measured by their examination performance. One hour EFAST training and 4 -hours
      practice provide an acceptable level of skill for medical students. The EFAST
      final marks showed significant weak correlation with other OSCE station marks and
      final clerkship marks, but not with the final MCQ exam mark which assesses a
      different cognitive learning domain.

PMID- 30191189
TI  - Factors predicting the need for tube thoracostomy in patients with iatrogenic
      pneumothorax associated with computed tomography-guided transthoracic needle
      biopsy.
AB  - Objectives: Traumatic iatrogenic pneumothorax occurs most often after a
      transthoracic needle biopsy. Since this procedure has become a common outpatient
      intervention, emergency department admissions of post-biopsy pneumothorax
      patients have increased. The aim of this study was to determine the factors that
      predict the need for tube thoracostomy in patients with post-biopsy pneumothorax
      in the emergency department. Methods: A retrospective cross-sectional study was
      conducted on 191 patients with post-biopsy pneumothorax who were admitted to the
      emergency department between 2010 and 2017. Patient characteristics, clinical
      findings at the emergency department presentation, and procedural and
      radiological features were reviewed. A multivariate logistic regression model was
      constructed using the variables from univariate comparisons to determine the need
      for tube thoracostomy in patients with iatrogenic pneumothorax, and the effect
      sizes were demonstrated with odds ratios. Results: Tube thoracostomies were
      performed on 69 out of 191 patients (36.1%). A total of 122 patients (63.9%) were
      treated with supplemental oxygen therapy without any other intervention, and 126
      patients (66.0%) were hospitalized. In the multivariate model, the variables
      predicting the need for a tube thoracostomy were decreased breath sounds,
      dyspnea, decreased systolic blood pressure, decreased oxygen saturation and
      increased pleura-lesion distance. A distance of 19.7 mm predicted the need with a
      sensitivity of 69.6% and a specificity of 62.3%. Conclusion: Decreased breath
      sounds, dyspnea, decreased systolic blood pressure, decreased oxygen saturation,
      and increased pleura-lesion distance may predict the need for a tube thoracostomy
      in patients with post-biopsy pneumothorax.

PMID- 30191190
TI  - The diagnostic accuracy of ultrasonography in determining the reduction success
      of distal radius fractures.
AB  - Objective: We evaluated the sensitivity and specificity of bedside ultrasound
      (US) for determining the success of reduction of displaced distal radius
      fractures. In addition, we determined the ability of US to diagnose causes of
      unsuccessful reduction. Methods: In a prospective, double-blind fashion, patients
      over 18 of age whose acute distal radius fracture was to be reduced were
      approached for inclusion. The closed reductions were performed by orthopedics
      residents. Post-reduction, the fracture was checked by an Emergency Medicine (EM)
      resident by US. Ultrasound images were evaluated by an EM attending physician
      blinded to X-ray findings and post-reduction X-ray images were evaluated by an
      orthopedic surgeon blinded to the US findings. Results: Sixty patients agreed to
      participate in the study. Of these, reduction was deemed successful by X-ray in
      40 (66.7%). Of these 40, 39 (97.5%) were found to be successful reductions by US.
      In the 20 of 60 (33.3%) patients with unsuccessful reduction by X-ray, 19 (95%)
      were considered unsuccessful reductions by US. In evaluating the success of
      distal radius fracture reduction, compared to X-rays, US was 97.5% (95% CI 86.8
      to 99.9) sensitive and 95% (95% CI 75.1 to 99.9) specific; its positive
      predictive value was 97.5% (95% CI 85.2 to 99.6) and negative predictive value
      95% (95% CI 73.2 to 99.2). Conclusions: Ultrasonography is highly sensitive and
      specific in determining the success of distal radius fracture reduction.

PMID- 30191191
TI  - Emergency medicine physicians' perspectives on subspecialty training: A national
      survey.
AB  - Background: Subspecialty training (sST) is an accepted educational model for the
      branches that have completed the maturation period. At the end of a rapid growth
      and reaching its limits, we wanted to determine the emergency medicine (EM)
      physicians' thoughts about subspecialty training in EM in Turkey. Method: This is
      a national cross-sectional survey study conducted in November 2017. Participants
      were physicians who were receiving or who had completed emergency medicine
      education. Results: The response rate was 32% (n = 607) in the study. The rate of
      attending physicians was 45.1%, resident physicians were 40.2%, and academic
      staff were 14.7%. Among all the EM physicians, 85.2% noted the need for sST, 9.6%
      were uncertain about the need, and 5.3% found the need unnecessary. The most
      frequently requested trainings were toxicology (72.5%), traumatology (71.3%), and
      critical care (67.4%). After sST, 48.9% of EM physicians requested to work both
      in the emergency department and in the other relevant department, 36.1% requested
      to work full-time in the emergency department, and 14.9% requested to work full
      time in the other relevant department. Conclusion: The great majority of EM
      physicians believed in the need for sST in Turkey. There were two primary reasons
      for wanting to apply for sST: first, and most frequently, was the contribution to
      advanced training, and second, was avoiding problems in the daily practice of EM.

PMID- 30191192
TI  - Non-urgent adult patients in the emergency department.

PMID- 30191193
TI  - Description of non-urgent patients in the emergency department.

PMID- 30191194
TI  - A diagnostic negative ultrasound finding in blunt abdominal trauma.
AB  - Introduction: Ultrasound is an extension of the clinical examination and its
      findings should be correlated with the clinical picture as a whole to be useful.
      Hereby, we report a unique negative diagnostic ultrasound finding in blunt
      abdominal trauma which was not reported before. Clinical presentation: A 50-year
      old obese man presented complaining of severe generalized abdominal pain and
      inability to pass urine of three days duration after he slipped on his abdomen.
      The abdomen was distended and tender all over. There was no blood on the urethral
      meatus. FAST scan showed significant intra-peritoneal fluid. The urinary bladder
      could not be seen. A Foley catheter was inserted which drained 3 L of clear
      urine. The abdominal distention became less. Repeated FAST scan was completely
      negative. A clinical diagnosis of major intra-peritoneal rupture of the urinary
      bladder was made. Trauma CT scan and laparotomy confirmed the diagnosis.
      Conclusions: The change of a positive FAST to a negative FAST was diagnostic of a
      major intra-peritoneal urinary bladder rupture even before performing a trauma CT
      scan. When performing FAST in blunt abdominal trauma, it is more useful to
      perform FAST before inserting a urinary catheter and it is advised to repeat it.

PMID- 30191195
TI  - Transient visual loss: Transient lesion in the splenium of the corpus callosum.
AB  - Background: The corpus callosum is the most important pathway enabling the
      exchange of information between the two cerebral hemispheres. Transient splenium
      lesions may develop in association with various pathologies and infections. We
      report a case presenting to the emergency department with transient visual loss
      and in which a transient lesion was determined in the splenium of the corpus
      callosum (SCC). Case report: A 24-year-old woman presented to the emergency
      department due to sudden onset visual loss. An area of restricted diffusion was
      determined in the SCC at diffusion magnetic resonance imaging (MRI) of the brain.
      The patient was admitted to the ward with a diagnosis of SCC lesion. The lesion
      had resolved entirely at control MRI performed 2 weeks later. Conclusion: There
      may be many causes of transient SCC lesions, and patients may present with
      different clinical manifestations, particularly altered consciousness and rarely
      visual loss like our present case.

PMID- 30191196
TI  - The coexistence of Wolff-Parkinson-White syndrome (WPW) and atrioventricular
      nodal reentrant tachycardia (AVNRT).
AB  - Atrioventricular nodal reentrant tachycardia (AVNRT) is the most common type of
      reentrant paroxysmal supraventricular tachycardia that occurs in the presence of
      dual AV nodal physiology. Wolff-Parkinson-White (WPW) syndrome is another type of
      supraventricular tachycardia characterized by short PR intervals, delta waves and
      wide QRS complexes on the surface electrocardiogram (ECG), reflecting
      atrioventricular pre-excitation. Uncommonly, AV nodal reentry and accessory
      pathways can coexist. In this case report, we present a patient who had frequent
      episodes of palpitation and syncope and recently presented to the emergency
      department (ED) with the complaint of dizziness. We performed successful
      radiofrequency (RF) catheter ablation of mitral annulus posterolateral accessory
      pathway and AVNRT which was the cause of the second tachycardia induced during
      the same session.

PMID- 30191197
TI  - A case of headache, double vision and ptosis in emergency department: Tolosa-Hunt
      syndrome.
AB  - Headache and double vision symptoms can be seen especially neurological and
      optical problems. We present Tolosa-Hunt syndrome in a 34-year-old female patient
      who presented to the emergency department (ED) with the complaints of unilateral
      severe headache, double vision and ptosis, presented asymmetric contrast
      enhancement in the right superior cavernous sinus on MR. This pain was reduced
      with steroid therapy. Pulse steroid therapy of 1 mg/kg/day was planned based on
      the patient's clinical manifestation, MRI findings and presumed diagnosis of THS.
      It was observed at patient's follow-up that there were occasional headache,
      ptosis and double vision were disappeared and MRI findings were regressed. In the
      differential diagnosis of patients presenting to the ED with the complaints of
      headache and double vision, rare pathologies such as THS should be considered in
      addition of common pathologies such as neurological and ocular diseases.

PMID- 30191198
TI  - Can water lacerate a tendon? A car-wash accident: A lacerated extensor hallucis
      longus tendon.
AB  - Our purpose in this report, involving an unusual mechanism described for the
      first time in the literature, is to show that high-pressure water sprays used for
      washing cars can cause injury to the extensor hallucis longus (EHL). A 21-year
      old man presented to our emergency department (ED) due to looseness in the
      hallux. His history revealed that while operating a pressurized water spray
      machine for car-washing one week before, he had inadvertently sprayed his foot,
      and despite wearing protective plastic boots this had resulted in a laceration at
      the level of the hallux, which had been sutured in a state hospital. Cleaning
      equipment using pressurized water can be dangerous if sufficient safety measures
      are not taken. We think that such occupational accidents with serious outcomes
      can be prevented through simple protective measures.

PMID- 30191199
TI  - Food Systems: Pathways for Improved Diets and Nutrition.
AB  - The United Nations has declared 2016-2025 as the Decade of Action on Nutrition.
      The emphasis of this decade is on alleviating malnutrition in all its forms. Food
      systems are 1 of 6 priorities for achieving this goal. This brief uses a food
      systems approach to analyze the effects of agriculture production,
      commercialization, and sex on diet quality and nutrition.

PMID- 30191200
TI  - Improving Health while Alleviating Hunger: Best Practices of a Successful Hunger
      Relief Organization.
AB  - Background: Food insecurity affects millions each year in the United States.
      Hunger relief organizations work to reduce hunger and food insecurity; however,
      the foods they provide are often unhealthy. Objective: The objective of this
      article is to document the policy, systems, and environmental changes that
      Samaritan Community Center made to their programs in order to better serve
      Washington County and Benton County, Arkansas. Methods: With the use of a case
      study approach, researchers held 17 meetings with key members of the organization
      and conducted >30 h of observations to document policy, systems, and
      environmental changes and best practices for implementing those changes. Results:
      Researchers identified emergent themes and grouped best practices in the
      following categories: 1) removing stigma and empowering clients, 2) incremental
      steps to increase access to healthy foods, 3) embracing multiculturalism, 4)
      donation policies and procurement, 5) collaboration is key, 6) organizational
      culture, and 7) challenges and resolutions. Conclusions: Samaritan Community
      Center has successfully implemented and adopted new programs and practices in
      order to improve the health of their clients. To our knowledge, this is the first
      case study to document best practices for making policy, systems, and
      environmental changes by a hunger relief organization to improve the nutritional
      quality of foods provided to their clients.

PMID- 30191201
TI  - Seasonality of Consumption of Nonstaple Nutritious Foods among Young Children
      from Nepal's 3 Agroecological Zones.
AB  - Background: Children's dietary patterns vary seasonally, particularly in
      subsistence agriculture settings like Nepal, but the seasonality of nutritious
      nonstaple food consumption is not well explored in the literature. Objective:
      This study aimed to examine seasonal differences in children's consumption of
      provitamin A-rich fruit and vegetables, dairy, eggs, meat, and fish in Nepal's 3
      agroecological zones, and to assess whether seasonal patterns vary by wealth and
      caste/ethnicity. Methods: Multivariable negative binomial regression models were
      used to analyze dietary data from 7-d food-frequency questionnaires, producing
      coefficient estimates in the form of incidence rate ratios (IRRs). Data were
      collected 3 times per year for 2 y from children aged 6-72 mo in Nepal's
      mountains (n = 226), hills (n = 168), and plains (n = 225). Results: There were
      significant seasonal differences in children's consumption of provitamin A-rich
      fruit and vegetables, dairy, meat, and fish that varied by agroecological zone.
      Adopting monsoon season as the referent for all comparisons, children in the
      mountains ate provitamin A-rich fruit and vegetables less frequently during the
      postmonsoon and winter seasons (IRRs: 0.5 and 0.7, respectively; both P < 0.004),
      whereas in the plains, children's consumption of these foods was lower only
      during the postmonsoon season (IRR: 0.2; P < 0.001). Children's dairy intake
      frequency increased during the winter in the mountains (IRR: 0.7; P < 0.004) and
      decreased during the winter in the hills (IRR: 1.5; P < 0.001). Only in the
      plains did children's meat and fish intakes vary seasonally, increasing during
      the postmonsoon season (IRR: 1.6; P < 0.004). Wealth and caste/ethnicity
      variability influenced children's consumption of each of these nutritious groups
      of foods, and moderated seasonal effects in some instances. Conclusions:
      Children's diets varied differently by season within each agroecological zone of
      Nepal and in some cases across socioeconomic groups, revealing the importance of
      taking a season- and location-specific approach to assessing diets and tailoring
      dietary strategies.

PMID- 30191203
TI  - Adaptive Visual Sort and Summary of Micrographic Images of Nanoparticles for
      Forensic Analysis.
AB  - Image classification of nanoparticles from scanning electron microscopes for
      nuclear forensic analysis is a long, time consuming process. Months of analyst
      time may initially be required to sift through images in order to categorize
      morphological characteristics associated with nanoparticle identification.
      Subsequent assessment of newly acquired images against identified characteristics
      can be equally time consuming. We present INStINCt, our Intelligent Signature
      Canvas, as a framework for quickly organizing image data in a web-based canvas
      framework that partitions images based on features derived from convolutional
      neural networks. This work is demonstrated using particle images from an aerosol
      study conducted by Pacific Northwest National Laboratory under the auspices of
      the U.S. Army Public Health Command to determine depleted uranium aerosol doses
      and risks.

PMID- 30191204
TI  - Using Wearable Activity Type Detection to Improve Physical Activity Energy
      Expenditure Estimation.
AB  - Accurate, real-time measurement of energy expended during everyday activities
      would enable development of novel health monitoring and wellness technologies. A
      technique using three miniature wearable accelerometers is presented that
      improves upon state-of-the-art energy expenditure (EE) estimation. On a dataset
      acquired from 24 subjects performing gym and household activities, we demonstrate
      how knowledge of activity type, which can be automatically inferred from the
      accelerometer data, can improve EE estimates by more than 15% when compared to
      the best estimates from other methods.

PMID- 30191202
TI  - Validity of the Food Insecurity Experience Scale for Use in Sub-Saharan Africa
      and Characteristics of Food-Insecure Individuals.
AB  - Background: The Food Insecurity Experience Scale (FIES) is a UN FAO-Voices of the
      Hungry project (FAO-VoH) metric of food insecurity (FI). The FAO-VoH tested the
      psychometric properties of FIES with the use of global 2014 Gallup World Poll
      (GWP) data. However, similarities in its psychometric structure in sub-Saharan
      Africa (SSA) to allow aggregation of SSA results were untested. Objectives: We
      aimed to 1) assess the validity of FIES for use in SSA, 2) determine the
      prevalence of FI by country, age group, and gender, and 3) examine the
      sociodemographic and economic characteristics of individuals with FI. Methods:
      The Rasch modeling procedure was applied to data collected by GWP in 2014 and
      2015 on 57,792 respondents aged >=19 y in SSA. Results: FIES largely met the
      Rasch model assumptions of equal discrimination and conditional independence.
      However, 34.3% of countries had high outfits (>=2.0) for the item "went without
      eating for a whole day." Four countries had significant correlations for the
      items "were hungry but did not eat" and "ran out of food." The overall prevalence
      of severe FI (SFI) was 36.4%, ranging from 6.0% in Mauritius to 87.3% in South
      Sudan. Older adults were at significantly higher risk of SFI than younger adults
      (38.6% and 35.8%, respectively, P < 0.0001), and women more than men (37.3% and
      35.4%, respectively, P < 0.0001). Higher proportions of individuals with SFI were
      rural residents, less educated, lower income, unemployed, and lived in households
      with many children under the age of 15 y. Conclusions: FIES has acceptable levels
      of internal validity for use in SSA. However, the item "went without eating for a
      whole day" may need cognitive testing in a few SSA countries. For countries with
      correlated items, 1 of the items may be excluded.

PMID- 30191205
TI  - Tuning core-shell interactions in tungsten carbide-Pt nanoparticles for the
      hydrogen evolution reaction.
AB  - Platinum (Pt) is among the best electrocatalysts for the hydrogen evolution
      reaction (HER), a potentially fossil-free route for hydrogen production.
      Reduction in Pt loading and overall catalyst cost, without sacrificing catalytic
      activity, can be achieved by the synthesis of stable core-shell nanoparticles of
      transition-metal carbides and Pt. We employ density-functional theory (DFT)
      calculations to study and contrast the suitability of the alpha and beta phases
      of tungsten carbide (WC) as support (core) materials for Pt shells. We examine
      the thermodynamic stability of 1-2 layers of Pt on alpha- and beta-WC surfaces,
      carefully accounting for the delicate balance between epitaxial mismatch strains
      and chemical bonding between cores and shells. We also study the effects of
      alloying beta-WC with Ti to modulate the stability and electronic structure of
      the core-shell structures. We compare the electronic structures of Pt overlayers
      supported on alpha-WC and beta-TixW1-xC surfaces and compare their activities for
      HER using the hydrogen binding energy as a descriptor of catalytic activity. Our
      studies reveal that moderate Ti doping of the metastable beta-WC phase
      significantly improves its stability and, with merely two layers of Pt loading,
      HER activity comparable or superior to Pt(111) can be attained. Overall, our
      results provide detailed insight into experimental observations of the excellent
      stability and high catalytic activity of beta-TixW1-xC@Pt core-shell
      nanoparticles.

PMID- 30191206
TI  - Improved charge carrier dynamics in polymer/perovskite nanocrystal based hybrid
      ternary solar cells.
AB  - Here, brand new ternary hybrid solar cells comprising perovskite nanocrystals
      (NCs) with a complementary absorption profile of the organic host matrix are
      reported. In particular, NH2CH[double bond, length as m-dash]NH2PbI3 (FAPbI3)
      perovskite NCs are implemented in bulk heterojunction organic solar cells based
      on the pDPP5T-2 electron donating polymer and a [6,6]-phenyl-C61-butyric acid
      methyl ester (PC61BM) acceptor at various loading amounts and the fabricated
      hybrid photovoltaics are thoroughly studied by employing different optoelectrical
      characterization methods. Current-voltage measurements and photoinduced charge
      carrier extraction by linear increasing voltage (photo-CELIV) reveal improved
      charge generation and charge transport properties upon incorporation of
      perovskite NCs into the photo-active layer of the hybrid solar cell. The power
      conversion efficiency (PCE) of the hybrid solar cell comprising 5% perovskite NCs
      is 10% enhanced compared to the organic reference, mainly due to the enlarged
      light harvesting and increased short circuit current density (Jsc). However,
      results suggest that introducing a higher amount of perovskite content induces
      bimolecular and trap-assisted recombination in the ternary devices. We perform a
      comprehensive transient absorption study of the charge transfer/transport
      mechanisms by employing femto-second pump-probe transient absorption spectroscopy
      (fs-TAS). fs-TAS measurements demonstrate a slower charge carrier recombination
      rate due to the introduction of perovskite NCs into the photoactive layer.
      Results reveal that DPP injects electrons from the singlet excited state into the
      perovskite NCs, which causes the desired cascading charge carrier transfer. In
      ternary blends, a small amount of FAPbI3 NCs provides an additional pathway in
      favor of the charge-separated state via the NCs, which, despite accelerating the
      depopulation of DPP's singlet excited state slightly slows down the charge
      separation process between DPP and PC61BM. Interestingly, the loss processes are
      slowed down; an effect that is more important and, hence, explains the improved
      solar cell efficiency.

PMID- 30191208
TI  - Double resonance rotational spectroscopy of He-HCO.
AB  - The ground state of He-HCO+ is investigated using a recently developed double
      resonance technique, consisting of a rotational transition followed by a
      vibrational transition into a dissociative state. In order to derive precise
      predictions for the rotational states, the high resolution infrared
      predissociation spectroscopy of the v1 C-H stretching mode is revisited. Eleven
      pure rotational transitions are measured via the double resonance method. A least
      squares fit of these transitions to a standard linear rotor Hamiltonian reveals
      that the semirigid rotor model cannot fully describe the loosely bound He-HCO+
      complex. The novel double resonance technique is compared with other action
      spectroscopic schemes, and some potential future applications are presented.

PMID- 30191209
TI  - Revealing the role of phosphoric acid in all-vanadium redox flow batteries with
      DFT calculations and in situ analysis.
AB  - The present work suggests the use of a mixed water-based electrolyte containing
      sulfuric and phosphoric acid for both negative and positive electrolytes of a
      vanadium redox flow battery. Computational and experimental investigations reveal
      insights on the possible interactions between the vanadium ions in all oxidation
      states and sulphate, bisulphate, dihydrogen phosphate ions and phosphoric acid.
      In situ cycling experiments and ion-specific electrochemical impedance
      measurements confirmed a significant lowering of the charge-transfer resistance
      for the reduction of V(iii) ions and, consequently, an increase of the voltaic
      efficiency associated with the negative side of the battery. This increase of
      performance is attributable to the complexation of this oxidation state by
      phosphoric acid. So far, mixed acids have mainly been discussed with the focus on
      V(v) solubility. In this work we rationalize the impact of the mixed acids on the
      electrochemical efficiency opening new strategies on how to improve the cycling
      performance with ionic additives.

PMID- 30191207
TI  - Electron transfer characteristics of 2'-deoxy-2'-fluoro-arabinonucleic acid, a
      nucleic acid with enhanced chemical stability.
AB  - The non-biological nucleic acid 2'-deoxy-2'-fluoro-arabinonucleic acid (2'F-ANA)
      may be of use because of its higher chemical stability than DNA in terms of
      resistance to hydrolysis and nuclease degradation. In order to investigate the
      charge transfer characteristics of 2'F-ANA, of relevance to applications in
      nucleic acid-based biosensors and chip technologies, we compare the electronic
      couplings for hole transfer between stacked nucleobase pairs in DNA and 2'F-ANA
      by carrying out density functional theory (DFT) calculations on geometries taken
      from molecular dynamics simulations. We find similar averages and distribution
      widths of the base-pair couplings in the two systems. On the basis of this
      result, 2'F-ANA is expected to have charge transfer properties similar to those
      of DNA, while offering the advantage of enhanced chemical stability. As such, 2'F
      ANA may serve as a possible alternative to DNA for use in a broad range of
      nanobiotechnological applications. Furthermore, we show that the (experimentally
      observed) enhanced chemical stability resulting from the backbone modifications
      does not cause reduced fluctuations of the base-pair electronic couplings around
      the values found for "ideal" B-DNA (with standard step parameter values). Our
      study also supports the use of a DFT implementation, with the M11 functional, of
      the wave function overlap method to compute effective electronic couplings in
      nucleic acid systems.

PMID- 30191210
TI  - Elemental tellurium mediated synthesis of 2-(trifluoromethyl)oxazoles using
      trifluoroacetic anhydride as reagent.
AB  - An elemental tellurium mediated synthesis of 2-(trifluoromethyl)oxazoles from the
      reaction of acetophenone oxime acetates with trifluoroacetic anhydride has been
      developed. This new tandem cyclization proceeds in good to excellent yields via a
      SET reduction followed by a 5-endo-trig pathway. Some of the title compounds
      showed fungicidal and insecticidal activities.

PMID- 30191211
TI  - Statistical thermodynamics for the unexpectedly large difference between
      disaccharide stereoisomers in terms of solubility in water.
AB  - We unravel the physical origins of the large difference between cellobiose and
      maltose, which consist of two beta-1,4 and alpha-1,4 linked d-glucose units,
      respectively, in terms of the solubility in water. We construct a thermodynamic
      theory where the chemical-potential difference between disaccharides in water and
      in vacuum is identified as the key free-energy function. Its energetic and
      entropic components are calculated for cellobiose and maltose by statistical
      mechanical theories for solute hydration. The disaccharide structures are taken
      into account at the atomic level and a molecular model is adopted for water.
      Molecular dynamics simulations are used to account for the conformational
      fluctuation of a disaccharide molecule, which also enables us to estimate the
      conformational entropy. We show that the cellobiose/maltose solubility ratio
      calculated is in good agreement with the experimental value. The solubility
      becomes much lower for cellobiose due to conformational-entropy and water-entropy
      effects. The former effect is relevant to higher stability of the intramolecular
      hydrogen bond between oxygen atoms in the six-membered ring and in the
      neighboring hydroxyl group: the hydration alters the fluctuation of a molecular
      conformation to a larger or less regular one, but the degree of this alteration
      is smaller. The latter effect is attributed to more separation of two
      hydroxymethyl groups in a molecule, causing lower probability of the overlap of
      excluded volumes generated by the groups for water molecules. We suggest that
      physicochemical properties of disaccharides in water become variable depending on
      the stereoisomerism through hydration effects and the origins of the variety are
      entropic.

PMID- 30191212
TI  - pi-Hole/n->pi* interactions with acetonitrile in crystal structures.
AB  - A thorough analysis of the Cambridge Structure Database shows that pi-hole/n->pi*
      interactions with acetonitrile are abundant in the solid state, particularly when
      acetonitrile is coordinated to a metal. The interaction is weakly directional (P
      <= 1.5) and high level computations suggest a complexation energy of about -5
      kcal mol-1.

PMID- 30191213
TI  - The prediction of far-infrared spectra for planetary nitrile ices using periodic
      density functional theory with comparison to thin film experiments.
AB  - Future spacecraft missions to planetary systems, Trans-Neptunian objects, and
      cometary bodies could implement far-infrared surveys to confirm the presence of
      condensed-phase species via their unique lattice features. For composite
      molecular ices of astrophysical significance, laboratory reference spectra are
      required to provide absorption coefficients used to quantify solid-state
      abundances. However, due to strong intermolecular interactions in polar ice
      systems, laboratory data of mixed-phase ices are difficult to interpret. In this
      study we have applied periodic density functional theory code to model bulk
      molecular crystals. This method allows for more accurate simulation of thin-film
      spectra than approaches simulating small clusters. For this proof-of-principle
      study on a series of pure nitrile ices of planetary interest, our simulated far
      infrared spectra show excellent agreement to data from thin film studies
      performed at the Australian Synchrotron (crystalline acetonitrile and
      propionitrile) and to previously published spectra (hydrogen cyanide,
      acrylonitrile, cyanoacetylene, and cyanogen). The combined theoretical and
      experimental approach has provided a new explanation for the asymmetric profile
      of the hydrogen cyanide lattice feature and a more systematic assignment of
      nitrile ice absorption bands to low-frequency lattice modes. We nominate
      prominent absorption features for the detection of crystalline nitrile carriers
      located on planetary surfaces.

PMID- 30191214
TI  - Stability of hydrolytic arsenic species in aqueous solutions: As3+vs. As5.
AB  - Notwithstanding the fact that arsenic compounds are ubiquitous in the As3+ and
      As5+ forms in aqueous solutions, most of the microscopic features underlying the
      conditions of the hydrolysis steps are completely unknown. This way, a first
      principles description of the fundamental behaviour of common arsenic species in
      natural waters and biological fluids is still lacking. Here we report on a
      synergistic computational and experimental investigation on As3+ and As5+
      speciation in aqueous solution under both standard and sizably different alkaline
      circumstances. If, on the one hand, ab initio molecular dynamics simulations have
      been used to microscopically trace the different hydrolysis steps of As3+ and
      As5+ by explicitly taking into account the solvent contribution, on the other
      hand, they have been able to identify - and predict - the most stable hydrolytic
      species. In addition, by means of potentiometric and calorimetric measurements,
      the thermodynamic parameters (log K, DeltaH, and TDeltaS) have been determined at
      different ionic strength values (0 < I <= 1 mol L-1). By comparing the
      computational and the experimental findings of the species distribution under
      conditions of some biological fluids, a qualitative agreement on the compounds
      formed by As3+ and As5+ is thoroughly recorded and, therefore, the stable
      hydrolytic arsenic species present in natural waters and other biosystems are
      fully characterised.

PMID- 30191215
TI  - Microfluidic affinity separation chip for selective capture and release of label
      free ovarian cancer exosomes.
AB  - Exosomes are nanoscale vesicles found in many bodily fluids which play a
      significant role in cell-to-cell signaling and contain biomolecules indicative of
      their cells of origin. Recently, microfluidic devices have provided the ability
      to efficiently capture exosomes based on specific membrane biomarkers, but
      releasing the captured exosomes intact and label-free for downstream
      characterization and experimentation remains a challenge. We present a
      herringbone-grooved microfluidic device which is covalently functionalized with
      antibodies against general and cancer exosome membrane biomarkers (CD9 and EpCAM)
      to isolate exosomes from small volumes of high-grade serous ovarian cancer
      (HGSOC) serum. Following capture, intact exosomes are released label-free using a
      low pH buffer and immediately neutralized downstream to ensure their stability.
      Characterization of captured and released exosomes was performed using
      fluorescence microscopy, nanoparticle tracking analysis, flow-cytometry, and SEM.
      Our results demonstrate the successful isolation of intact and label-free
      exosomes, indicate that the amount of both total and EpCAM+ exosomes increases
      with HGSOC disease progression, and demonstrate the downstream internalization of
      isolated exosomes by OVCAR8 cells. This device and approach can be utilized for a
      nearly limitless range of downstream exosome analytical and experimental
      techniques, both on and off-chip.

PMID- 30191216
TI  - Small volume method for drug release screening using ultrasonic agitation.
AB  - Drug release testing plays a major role along all parts of the dosage form
      development and manufacturing process. However, official methods to perform this
      type of testing are often resource intensive and require highly specialized
      facilities. Affordable and accessible methods for studying drug release behavior
      are currently lacking. This work presents a small volume approach to solid
      dissolution and drug release testing of solid dosage forms using ultrasonic
      agitation. Cavitation and acoustic streaming were generated by a microprobe horn
      delivering a 40 kHz acoustic signal into a 50 mL test vessel. These two phenomena
      resulted in breakdown of and release of drug from tablet samples. Prednisone
      Performance Verification Tablets were used as model tablets to study the effect
      of system parameters on the drug release process. The effects of these parameters
      on the acousto-hydrodynamic environment were studied using streak photography and
      hydrophone measurements. Drug release behavior showed a slow/fast threshold
      transition separated by a highly variable regime as a function of the system
      parameters. Observations from drug release experiments and results from acoust
      hydrodynamic characterization experiments suggested that this transition is
      dominated by acoustic streaming. This method represents a screening method to
      probe relative differences in dosage form composition and acts as a complimentary
      approach to official testing methods. The small volume format of this test has
      potential applications in the study of drug release properties from low-dose and
      novel solid dosage forms as well as reduced cost and increased accessibility of
      release testing for post-manufacturing tablet quality screening, a current need
      in low- and middle-income countries.

PMID- 30191219
TI  - A histidine-rich Pseudomonas metallothionein with a disordered tail displays
      higher binding capacity for cadmium than zinc.
AB  - Metallothioneins (MTs) are crucial players in metal-related physiological
      processes. They are characterized by a high cysteine content and unique metal
      binding properties resulting in specific metal-thiolate clusters formation. Here
      we present the first NMR solution structure of a Pseudomonas MT, PflQ2 MT, using
      the strain P. fluorescens Q2-87. It consists of a metal binding domain and an
      intrinsically disordered C-terminal tail, that was not observed in other MTs so
      far. While not influencing the structure or function of the metal binding domain,
      the tail contains a potential binding motif that might be important in so far
      undiscovered biological interactions. Unusual is the different metal binding
      capacity for three ZnIIversus four CdII ions that results in two novel metal
      cluster topologies. Nevertheless, the affinity for the fourth CdII ion is reduced
      due to transient coordination. PflQ2 MT contains an unusually large number of
      four histidine residues, of which only one is involved in metal ion binding. The
      three non-coordinating histidine residues influence neither the protein fold nor
      the stability in vitro. We demonstrate that reinstatement of a second
      coordinating histidine residue, observed for cyanobacterial MTs, in place of a
      non-coordinating residue in Pseudomonas MTs, decreases the kinetic lability of
      the cluster, while preserving the overall metal ion binding stability and the
      protein fold. Since high thermodynamic stability combined with high kinetic
      lability of metal binding are mechanistic features critical for the function of
      MTs, the observed replacement might be advantageous for Pseudomonas MTs with
      respect to metal ion handling in vivo.

PMID- 30191218
TI  - Copper-catalyzed tandem aerobic oxidative cyclization for the synthesis of 4
      cyanoalkylpyrrolo[1,2-a]quinoxalines from 1-(2-aminophenyl)pyrroles and
      cyclobutanone oxime esters.
AB  - A copper-catalyzed tandem ring-opening/cyclization reaction for the synthesis of
      4-cyanoalkylpyrrolo[1,2-a]quinoxalines from 1-(2-aminophenyl)pyrroles and
      cyclobutanone oxime esters has been developed. This reaction involves C-C bond
      cleavage and C-C and C-N bond constructions with good functional group tolerance.
      A wide range of products are obtained in moderate to good yields under mild
      conditions.

PMID- 30191217
TI  - Molecular dynamics modeling of Pseudomonas aeruginosa outer membranes.
AB  - Pseudomonas aeruginosa is a common Gram-negative bacterium and opportunistic
      human pathogen. The distinctive structure of its outer membrane (OM) and outer
      membrane vesicles (OMVs) plays a fundamental role in bacterial virulence,
      colonization ability, and antibiotic resistance. To provide critical insights
      into OM and OMV functionality, we conducted an all-atom molecular dynamics study
      of asymmetric membranes that are biologically relevant to P. aeruginosa. We
      hybridized a GLYCAM06-based lipopolysaccharides force field with the Stockholm
      lipids force field (Slipids) to model bilayer membranes with Lipid A molecules in
      one leaflet and physiologically relevant phospholipid molecules in the other,
      including 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE), 1,2-dioleoyl
      sn-glycero-3-phosphoethanolamine (DOPE), 1,2-dipalmitoyl-sn-glycero-3
      phosphoglycerol (DPPG), and 1,2-dioleoyl-sn-glycero-3-phosphoglycerol (DOPG). In
      particular, a membrane with phospholipid composition representing the P.
      aeruginosa OM was constructed and modeled by mixing the physiologically dominant
      components. The detailed structure of membranes was characterized by area per
      lipid, transmembrane mass and charge densities, radial distribution function
      (RDF), deuterium order parameter (SCD) of acyl chains, and inclination angles of
      phosphates and disaccharide in Lipid A. The membrane fluidity in equilibrium and
      the hydration of functional groups were probed and characterized quantitatively.
      The consistent properties of the Lipid A leaflets in different membranes
      demonstrate its compatibility with various phospholipids present in the P.
      aeruginosa OM. The more ordered acyl chains of Lipid A compared to the
      cytoplasmic cell membrane contribute to the low permeability of bacterial outer
      membrane. The findings of this computational investigation of P. aeruginosa OM
      will further the understanding of microbial pathogenesis and enable future study
      of OMV biogenesis.

PMID- 30191220
TI  - A simple fluorescent aptamer based assay coupled with fluorescence scanning
      capillary array for aflatoxin B1.
AB  - We developed a simple aptamer fluorescence assay for aflatoxin B1 (AFB1)
      detection by using an array of capillaries. The 34-nt aptamer having a single
      fluorescein (FAM) label on the 24th T nucleotide generated a remarkable
      fluorescence increase upon AFB1 binding. The use of fluorescence scanning
      capillary array allowed for the analysis of multiple samples with low sample
      consumption, showing advantages of simplicity, rapidity and high throughput
      analysis. The detection limit of AFB1 reached 0.5 nM. This assay has great
      potential for analysis in food safety and environmental monitoring.

PMID- 30191221
TI  - Crystal structures of ordered and plastic-crystalline phases of iso-butyllithium
      by X-ray powder diffraction.
AB  - Donor-unsupported iso-butyllithium consists of hexamers with an ordered triclinic
      structure at -80  degrees C (alpha-phase). At ambient temperature, the compound
      exists as an orthorhombic, remarkably stable, plastic-crystalline gamma-phase,
      which is built by disordered hexamers adopting a distorted face-centred cubic
      packing. Both structures were determined by X-ray powder diffraction.
      Additionally, an intermediate beta-phase is observed.

PMID- 30191222
TI  - Structure-property analysis of julolidine-based nonlinear optical chromophores
      for the optimization of microscopic and macroscopic nonlinearity.
AB  - Four NLO chromophores with different acceptors and modified julolidine donors
      were facilely synthesized to tune their intramolecular charge-transfer energy
      gaps for the investigation of the structure-property relationships. The
      photophysical properties of the UV-Vis absorption spectra, fluorescence spectra
      and solvatochromism were measured and analyzed to understand the effect of
      electron-donating strength and electron-withdrawing strength on intramolecular
      charge-transfer. Density functional theory calculations were carried out to
      investigate the electron density of the frontier orbitals, energy gap, molecular
      microscopic dipole moment and hyperpolarizability. The change tendency of the
      microscopic hyperpolarizability in different dielectric environments in
      association with the solvatochromism in absorption was analyzed. Meanwhile, the
      macroscopic electro-optic performance in relation to molecular structure
      variation and microscopic properties was further analyzed, revealing that
      chromophores with a larger solvatochromism exhibited higher microscopic
      hyperpolarizability and macroscopic electro-optic coefficients. Our investigation
      of the structure-property relationship gave a reliable insight into molecular
      design for high performance nonlinear optical chromophores.

PMID- 30191223
TI  - Studies toward the synthesis of strevertenes A and G: stereoselective
      construction of C1-C19 segments of the molecules.
AB  - Stereoselective synthesis of common C1-C19 skeletons of pentane macrolides
      strevertenes A and G possessing 10 stereogenic centers has been achieved using a
      flexible and convergent strategy. The salient features of this synthetic study
      include the Evans aldol reaction for the constructions of C2, C3, C13, and C14
      centers, CBS reduction for the generation of a C7 center, Hoveyda-Grubbs cross
      olefin metathesis for the synthesis of C8-C9 bond, and Wittig olefination for the
      installation of C16-C19 conjugated olefins.

PMID- 30191224
TI  - Borophene layers on an Al(111) surface - the finding of a borophene layer with
      hexagonal double chains and B9 nonagons using ab initio calculations.
AB  - We studied the stability of several borophene layers on an Al(111) surface and
      found a structure called 9R using ab initio calculations. This layer competes
      with chi3 and beta12 borophene layers and is made up of boron nonagons that form
      a network of hexagonal boron double chains. Remarkably, it has no B6 hexagon
      unlike other borophene layers. All three layers lie significantly lower in energy
      than the honeycomb layer recently reported on the Al(111) surface [W. Li, et al.,
      Sci. Bull., 2018, 63, 282]. We discuss the structural stability and electronic
      structures of different borophene layers in light of the role of the filling
      factor f of boron atoms in boron hexagons in a honeycomb layer as well as charge
      transfer from the Al substrate to the borophene layer as obtained from the Bader
      charge analysis. The electron localization function shows that the 9R layer has
      two-center bonding within the nonagon rings and three-center bonding between the
      rings. Calculations of the phonon spectra show that a free 9R layer is
      dynamically stable raising the hope of its isolation. The electronic structure
      shows that in all cases the borophene layer is metallic.

PMID- 30191225
TI  - Tailoring the interfacial structure of colloidal "giant" quantum dots for
      optoelectronic applications.
AB  - Colloidal semiconductor quantum dots (QDs) are promising building blocks for the
      realization of future optoelectronic technologies, thanks to their size-tunable
      electronic and optical properties. Among various types of QDs, colloidal "giant"
      QDs (g-QDs, core/thick-shell) have been widely used in different applications,
      such as solar cells, light emitting devices, luminescent solar concentrators and
      photoelectrochemical (PEC) hydrogen production. However, g-QDs have a thick-shell
      which serves as a physical barrier for electron and hole transfer, leading to a
      slow charge transfer rate. In this work, we synthesized CdSe/CdSexS1-x/CdS
      core/shell/shell g-QDs with an intermediate CdSexS1-x alloyed layer. The presence
      of this interfacial layer largely improves the absorption of CdSe/CdS QDs,
      particularly in the 300-650 nm range. By engineering the interfacial layer, the
      holes can leak more into the CdS shell region compared to that of CdSe/CdS QDs.
      PEC devices based on alloyed g-QDs exhibit a 20% higher saturated photocurrent
      density (11 +/- 0.5 mA cm-2) compared to CdSe/CdS QDs. In addition, after one
      hour illumination (100 mW cm-2), the PEC cell based on alloyed g-QDs still
      exhibits a photocurrent density of 7.5 mA cm-2, maintaining 70% of its initial
      value. Such alloyed g-QDs are very promising for several emerging optoelectronic
      applications, where charge separation, transfer and transport play a critical
      role for the realization of high performance devices.

PMID- 30191226
TI  - Continuum percolation-based tortuosity and thermal conductivity of soft superball
      systems: shape dependence from octahedra via spheres to cubes.
AB  - Understanding the effect of particle shape on the percolation threshold,
      tortuosity and thermal conductivity of soft (geometrical overlapping) particle
      systems is very crucial for the design and optimization of such materials,
      including colloids, polymers, and porous and fracture media. In this work, we
      first combine the excluded-volume theory with the Monte Carlo simulations to
      determine the percolation threshold for a family of soft superballs, the shape of
      which interpolates between octahedra and cubes via spheres. Then, we propose two
      continuum percolation-based models to respectively obtain the tortuosity and
      effective thermal conductivity of soft superball systems considering their
      percolation behavior, where monodisperse overlapping superballs are uniformly
      distributed in a homogeneous solid matrix. Specifically, both models cover the
      whole feasible range of superball volume fractions, including near the
      percolation threshold. Comparison with extensive experimental, numerical and
      theoretical results confirms that the present models are capable of precisely
      predicting the percolation threshold, tortuosity and thermal conductivity of such
      systems. Furthermore, we apply the proposed models to probe the influence of
      particle shape on these important parameters. Our results show that the
      decreasing percolation threshold and tortuosity as soft particles become more
      anisotropic is consistent with increasing conductivity. It suggests that the
      anisotropic-shaped inclusion phase is more conducting than the spherical
      inclusion phase. The present theoretical strategies and conclusions may provide
      sound guidance for the synthesis of colloidal and polymer superballs.

PMID- 30191227
TI  - Temperature-controlled sequential Suzuki-Miyaura reactions for preparing
      unsymmetrical terphenyls.
AB  - A one-pot protocol of double Suzuki-Miyaura reactions has been developed for the
      synthesis of unsymmetrical terphenyls. In the absence of a ligand, potassium
      bromophenyltrifluoroborate reacts with arylboronic acid and then sequentially
      with a hetero/aryl bromide by controlling the reaction temperature, providing
      unsymmetrical p- and m-terphenyl compounds in moderate to good overall yields.
      This protocol provides a convenient and practical approach to unsymmetrical
      terphenyls under ligand-free and aerobic conditions.

PMID- 30191228
TI  - Spider prey-wrapping silk is an alpha-helical coiled-coil/beta-sheet hybrid
      nanofiber.
AB  - Solid-State NMR results on 13C-Ala/Ser and 13C-Val enriched Argiope argentata
      prey-wrapping silk show that native, freshly spun aciniform silk nanofibers are
      dominated by alpha-helical (~50% total) and random-coil (~35% total) secondary
      structures, with minor beta-sheet nanocrystalline domains (~15% total). This is
      the most in-depth study to date characterizing the protein structural
      conformation of the toughest natural biopolymer: aciniform prey-wrapping silks.

PMID- 30191229
TI  - Grafting of porphyrin oligomers on single-walled carbon nanotubes by Hay
      coupling.
AB  - The fabrication of nanotube-based functional materials is still limited by the
      difficulty in incorporating highly engineered molecules onto the nanotube
      surface. To overcome this difficulty, the development of procedures involving two
      subsequent reaction steps on the nanotubes appeared particularly promising. It
      was previously demonstrated that "click chemistry" (CuAAC) permits efficiently
      functionalising nanotubes with a wide variety of materials (from inorganic to
      biological). In this work, we present an original strategy based on Hay coupling
      (i.e. the oxidative coupling between triple bonds) to fabricate nanotube
      porphyrin conjugates. Porphyrins containing ethynyl functional groups were
      attached on single-walled carbon nanotubes (SWNTs) bearing phenylacetylene groups
      and the resulting materials were fully characterised.

PMID- 30191230
TI  - Investigations of organic-inorganic hybrids based on homopiperidinium cation with
      haloantimonates(iii) and halobismuthates(iii). Crystal structures, reversible
      phase transitions, semiconducting and molecular dynamic properties.
AB  - A description of the thermal, structural, 1H NMR, electric and optical properties
      of four organic-inorganic hybrids, haloantimonates(iii) and halobismuthates(iii),
      based on homopiperidinium cation: (C6H14N)2SbCl5 (abbrev. HSC), (C6H14N)2SbBr5
      (HSB), (C6H14N)2BiCl6[H3O] (HBC), (C6H14N)2BiBr5 (HBB), is presented. The common
      feature of the crystal structures of the studied compounds is the 1D (one
      dimensional) chain for the anionic network in HSC, HSB and HBB, 1D hydrogen bond
      chain between 0D (zero-dimensional, isolated) BiCl6 octahedrons and hydronium
      moieties in HBC as well as a rich polymorphism in the solid state for all title
      compounds. The structures of the Sb(iii) and Bi(iii) derivatives are not
      isomorphous and they crystallize in the following space groups: HSC in P212121
      both at 280 and 150 K, HSB in Pmna and P212121 at 310 and 150 K, respectively,
      HBC in C2/m, C2/m and C2/c at 300, 260 and 200 K, respectively, and HBB in P21/n
      both at 280 and 200 K. The anionic networks are in the forms of either pseudo-
      and zig-zag chains or a chain of a hydrogen bond. The band gap values, using the
      Tauc plot as well as the ac and dc conductivity parameters, were estimated. On
      the basis of the 1H NMR spin-lattice relaxation times, T1, and second-moment, M2,
      measurements and the dielectric responses, the molecular mechanisms of the phase
      transitions (PTs) have been postulated. The structural PTs are discussed in terms
      of the changes in cationic dynamics and distortions of the anionic sublattice.
      The powder technique of SHG (Kurtz and Perry method) has been used to analyze the
      second-order nonlinear optical properties of HSC.

PMID- 30191231
TI  - Rapid diagnostics of liver steatosis by Raman spectroscopy via fiber optic probe:
      a pilot study.
AB  - Raman spectroscopy via fiber optic probes omits some of the major limitations
      related to ex vivo preparation of tissue samples (e.g. fixation, freezing,
      cutting) and enables rapid registration of spectra, therefore, this technique has
      the potential to become a useful diagnostic tool. In this work, we evaluated the
      applicability of Raman spectroscopy via fiber optic probe for rapid assessment of
      lipid content in the liver in the context of its potential application as a tool
      to verify the degree of liver steatosis. Non-alcoholic fatty liver disease
      (NAFLD) is a common liver disorder that is characterized by excessive lipid
      accumulation within hepatic tissue and is associated with insulin resistance and
      metabolic syndrome. Raman spectroscopy via fiber optic probe was applied to
      investigate the biochemical status of the liver in mild (mice fed a high-fat
      diet) and severe (db/db mice) models of NAFLD. A considerable increase in lipid
      content without substantial alterations in composition was observed in mild liver
      steatosis. In contrast, more severe liver steatosis caused not only a significant
      lipid content increase, but also hepatic cholesterol accumulation accompanied by
      significant loss of hepatic vitamin A content. Chemometric analysis based on
      average Raman spectra recorded via fiber optic probe provided discrimination of
      mild and severe liver steatosis and control livers with high sensitivity and
      specificity. In conclusion, our work demonstrates that a relatively simple Raman
      setup equipped with a commercial fiber optic probe combined with basic
      chemometric analysis enables rapid quantification of liver steatosis.

PMID- 30191232
TI  - Comparative study of the bioaccessibility of the colorless carotenoids phytoene
      and phytofluene in powders and pulps of tomato: microstructural analysis and
      effect of addition of sunflower oil.
AB  - The objective was to assess the potential bioavailability of phytoene (PT) and
      phytofluene (PTF) from tomato powders used as raw materials for supplements as
      compared to the pulp of a common tomato and a cherry tomato. PT and PTF are
      attracting much interest nowadays as they can provide health and cosmetic
      benefits. PT and PTF levels in the more concentrated powder were up to 1000 times
      higher than in the tomatoes. The bioaccessibility from the powders was lower as
      compared to the tomato fruits and increased markedly when sunflower oil was
      added. However, the best source of potentially absorbable PT and PTF (0.5 and 2
      mg g-1 respectively) was by far the powder with higher levels of them. This
      result could be due to the higher carotenoid concentration in the powder, the
      reduction of the particle sizes, and the rupture of cell structures compared to
      the pulps.

PMID- 30191233
TI  - Application of a quantum cascade laser aperture scanning near-field optical
      microscope to the study of a cancer cell.
AB  - This work reports the first images obtained by combining an infrared aperture
      scanning near-field optical microscope (SNOM) with a quantum cascade laser (QCL).
      The future potential of this set-up is demonstrated by a preliminary study on an
      OE33 human oesophageal adenocarcinoma cell in which the cell is imaged at 1751 cm
      1, 1651 cm-1, 1539 cm-1 and 1242 cm-1. In addition to the 1651 cm-1 image, three
      other images were acquired within the Amide I band (1689 cm-1, 1675 cm-1 and 1626
      cm-1) chosen to correspond to secondary structures of proteins. The four images
      obtained within the Amide I band show distinct differences demonstrating the
      potential of this approach to reveal subtle changes in the chemical composition
      of a cell.

PMID- 30191234
TI  - Self-assembled vertically aligned Ni nanopillars in CeO2 with anisotropic
      magnetic and transport properties for energy applications.
AB  - Self-assembled vertically aligned metal-oxide (Ni-CeO2) nanocomposite thin films
      with novel multifunctionalities have been successfully deposited by a one-step
      growth method. The novel nanocomposite structures presents high-density Ni
      nanopillars vertically aligned in a CeO2 matrix. Strong and anisotropic magnetic
      properties have been demonstrated, with a saturation magnetization (Ms) of ~175
      emu cm-3 and ~135 emu cm-3 for out-of-plane and in-plane directions,
      respectively. Such unique vertically aligned ferromagnetic Ni nanopillars in the
      CeO2 matrix have been successfully incorporated in high temperature
      superconductor YBa2Cu3O7 (YBCO) coated conductors as effective magnetic flux
      pinning centers. The highly anisotropic nanostructures with high density vertical
      interfaces between the Ni nanopillars and CeO2 matrix also promote the mixed
      electrical and ionic conductivities out-of-plane and thus demonstrate great
      potential as nanocomposite anode materials for solid oxide fuel cells and other
      potential applications requiring anisotropic ionic transport properties.

PMID- 30191235
TI  - Pathway driven self-assembly and living supramolecular polymerization in an
      amyloid-inspired peptide amphiphile.
AB  - Peptide 1 with an Abeta42 amyloid nucleating core demonstrates step-wise self
      assembly in water. Variation of temperature or solvent composition arrests the
      self-assembly to give metastable nanoparticles, which undergo self-assembly on
      gradual increase in temperature and eventually produce kinetically controlled
      nanofibers and thermodynamically stable twisted helical bundles. Mechanical
      agitation of the fibers provided access to short seeds with narrow polydispersity
      index, which by mediation of seeded supramolecular polymerization establishes
      perfect control over the length of the nanofibers. Such pathway dependence and
      the length control of the supramolecular peptide nanofibers is exploited to tune
      the mechanical strength of the resulting hydrogel materials.

PMID- 30191236
TI  - A novel fluorescent adhesive-assisted biomimetic mineralization.
AB  - We propose a novel fluorescent adhesive-assisted biomimetic mineralization
      strategy, based on which 1 wt% of sodium fluorescein and 25 wt% of polyacrylic
      acid stabilized amorphous calcium phosphate (PAA-ACP) nanoparticles were
      incorporated into a mild self-etch adhesive (Clearfil S3 Bond) as a fluorescent
      mineralizing adhesive. The characterization of the PAA-ACP nanoparticles
      indicates that they were spherical particles clustered together, each particle
      with a diameter of approximately 20-50 nm, in a metastable phase with two
      characteristic absorption peaks (1050 cm-1 and 580 cm-1). Our results suggest
      that the fluorescent mineralizing adhesive was non-cytotoxic with minimal
      esthetic interference and its fluorescence intensity did not significantly
      decrease within 6 months. Our data reveal that the fluorescent mineralizing
      adhesive could induce the extra- and intra-fibrillar remineralization of the
      reconstituted type I collagen, the demineralized enamel and dentin substrate. Our
      data demonstrate that a novel fluorescent adhesive-assisted biomimetic
      mineralization strategy will pave the way to design and produce anti-carious
      materials for the prevention of dental caries.

PMID- 30191238
TI  - Rational construction of a DNA nanomachine for HIV nucleic acid ultrasensitive
      sensing.
AB  - HIV nucleic acids, one kind of significant biomarker, play an important role in
      fundamental studies and clinical diagnosis. Importantly, the early accurate
      diagnosis for HIV nucleic acids at ultralow concentrations can potentially extend
      the life of patients. In the current work, we developed a DNA nanomachine on gold
      nanoparticles (AuNPs) coupling rolling circle amplification and DNA walker
      cascade amplification for ultrasensitive detection of HIV nucleic acids. This DNA
      nanomachine sensing strategy exhibits a significantly low detection limit down to
      1.46 fM. Furthermore, this DNA nanomachine biosensor is capable of detecting
      target DNA in real samples because of its high selectivity and sensitivity.
      Moreover, the DNA nanomachine biosensor is capable of discriminating single-base
      mismatch lower than 3.5 pM. The results showed that this DNA nanomachine
      biosensor has the potential for biomedical studies and clinical applications.

PMID- 30191239
TI  - A multi-signal mitochondria-targeted fluorescent probe for real-time
      visualization of cysteine metabolism in living cells and animals.
AB  - In this study, we developed a multi-signal mitochondria-targeted fluorescent
      probe (NIR-Cys) for simultaneous detection of Cys and its metabolite, SO2. In the
      design of the probe, the acrylate group and the C[double bond, length as m-dash]C
      of the coumarin ring were used as the recognizing moiety for Cys and SO2,
      respectively. The probe exhibited high sensitivity, excellent specificity, and
      fast response. NIR-Cys was found to precisely target and visualize Cys metabolism
      in mitochondria of living cells with a multi-fluorescence signal. This probe is
      expected to be a useful tool for understanding Cys metabolism.

PMID- 30191237
TI  - An all-in-one nanoparticle (AION) contrast agent for breast cancer screening with
      DEM-CT-MRI-NIRF imaging.
AB  - Conventional X-ray mammography has low diagnostic sensitivity for women with
      dense breasts. As a result, alternative contrast-enhanced screening tools such as
      dual energy mammography (DEM), computed tomography (CT), magnetic resonance
      imaging (MRI), and near-infrared fluorescence (NIRF) imaging are being used or
      investigated for these women. However, currently available contrast agents are
      non-ideal, have safety issues, and each imaging technique requires a different
      contrast agent. We therefore sought to develop a multimodal contrast agent that
      is functional for each breast imaging modality to simplify the diagnosis process
      and address the issues of existing contrast agents. Herein, we present a novel
      "all-in-one" nanoparticle (AION) multimodal imaging probe that has potent DEM,
      CT, MRI, and NIRF contrast properties and improved biocompatibility. AION were
      formed by co-encapsulation of a near-infrared fluorophore (DiR), silver sulfide
      nanoparticles (Ag2S-NP), and iron oxide nanoparticles (IO-NP) in PEGylated
      micelles. AION showed negligible cytotoxicity, which was in agreement with its
      minimal silver ion release profiles. AION generated strong contrast with all
      imaging modalities as demonstrated in phantom imaging. AION allowed in vivo tumor
      imaging as evidenced by the increase in contrast after injection. This study
      indicates the potential of AION as an effective multimodal contrast agent for
      breast cancer diagnosis with a range of imaging methods.

PMID- 30191240
TI  - Effect of ionic strength on the structure and elongational kinetics of vimentin
      filaments.
AB  - Intermediate filaments are a major structural element in the cytoskeleton of
      animal cells that mechanically integrate other cytoskeletal components and absorb
      externally applied stress. Their role is likely to be linked to their complex
      molecular architecture which is the product of a multi-step assembly pathway.
      Intermediate filaments form tetrameric subunits which assemble in the presence of
      monovalent salts to form unit length filaments that subsequently elongate by end
      to-end annealing. The present work characterizes this complex assembly process
      using reconstituted vimentin intermediate filaments with monovalent salts as an
      assembly trigger. A multi-scale approach is used, comprising static light
      scattering, dynamic light scattering and quantitative scanning transmission
      electron microscopy (STEM) mass measurements. Light scattering reveals the radius
      of gyration (Rg), molecular weight (Mw) and diffusion coefficient (D) of the
      assembling filaments as a function of time and salt concentration (cS) for the
      given protein concentration of 0.07 g L-1. At low cS (10 mM KCl) no lateral or
      elongational growth is observed, whereas at cS = 50-200 mM, the hydrodynamic
      cross-sectional radius and the elongation rate increases with cS. Rgversus Mw
      plots suggest that the mass per unit length increases with increasing salt
      content, which is confirmed by STEM mass measurements. A kinetic model based on
      rate equations for a two step process is able to accurately describe the
      variation of mass, length and diffusion coefficient of the filaments with time
      and provides a consistent description of the elongation accelerated by increasing
      cS.

PMID- 30191241
TI  - Two-component marangoni-contracted droplets: friction and shape.
AB  - When a mixture of propylene glycol and water is deposited on a clean glass slide,
      it forms a droplet of a given apparent contact angle rather than spreading as one
      would expect on such a high-energy surface. The droplet is stabilized by a
      Marangoni flow due to the non-uniformity of the components' concentrations
      between the border and the apex of the droplet, itself a result of evaporation.
      These self-contracting droplets have unusual properties such as absence of
      pinning and the ability to move under an external humidity gradient. The
      droplets' apparent contact angles are a function of their concentration and the
      external humidity. Here we study the motion of such droplets sliding down slopes
      and compare the results to normal non-volatile droplets. We precisely control the
      external humidity and explore the influence of the volume, viscosity, surface
      tension, and contact angle. We find that the droplets suffer a negligible pinning
      force so that for small velocities the capillary number (Ca) is directly
      proportional to the Bond number (Bo): Ca = Bo sin alpha with alpha the angle of
      the slope. Lastly we study the successive shapes the droplets take when sliding
      at larger and larger velocities.

PMID- 30191242
TI  - Diffusion mechanism of Na ion-polaron complex in potential cathode materials
      NaVOPO4 and VOPO4 for rechargeable sodium-ion batteries.
AB  - Using the density functional method, we investigated the crystal and electronic
      structures and the electrochemical properties of NaxVOPO4 (x = 0, 1) and explored
      the diffusion mechanism of Na ions in these materials. The van der Waals
      interaction was also taken into account to include the non-local electron
      correlation in the calculation of structural parameters and voltage. The
      diffusion of Na ions is treated as a process of the Na vacancy-positive small
      polaron complex in NaVOPO4 and the Na ion-negative small polaron complex in
      VOPO4, respectively. During the charging (discharging) process, the removal
      (insertion) of a Na ion would result in the formation of a positive (negative)
      small polaron at one of the two first nearest vanadium sites to the Na vacancy.
      Three elementary diffusion processes, including the single, crossing and parallel
      diffusion processes, are explored. It is found that the [010] direction is
      preferable for Na ion diffusion in both the charging and discharging processes.
      The influence of small polaron migration on Na ion diffusion in the charging
      state is negligible, whereas such effect is considerably strong in the
      discharging process. Moreover, while three elementary diffusion processes in
      NaVOPO4 require the same energy, the parallel diffusion process in VOPO4 is not
      preferred. The diffusion of Na vacancy accompanied by a positive polaron in the
      full charging process requires an activation energy of 395 meV, while the
      diffusion of Na ion accompanied by a negative polaron in the discharging state,
      VOPO4, has a higher activation energy of 627 meV. With a voltage and activation
      barrier similar to that of the olivine phosphate LiFePO4, these sodium-based
      materials are expected to be promising cathode materials for sodium ion
      batteries.

PMID- 30191243
TI  - Solid-state nanopore analysis on conformation change of p53TAD-MDM2 fusion
      protein induced by protein-protein interaction.
AB  - Although protein-protein interactions (PPIs) are emerging therapeutic targets for
      human diseases, development of high-throughput screening (HTS) technologies
      against PPI targets remains challenging. In this study, we propose a protein
      complex structure to effectively detect conformational changes of protein
      resulting from PPI using solid-state nanopore for a novel, widely-applicable drug
      screening method against various PPI targets. To effectively detect
      conformational changes resulting from PPI, we designed a fusion protein MLP (MDM2
      linker-p53TAD), where p53TAD and MDM2 are connected by a 16 amino acid linker.
      The globular conformation of MLP exhibited a single-peak translocation event,
      whereas the dumbbell-like conformation of nutlin-3-bound MLP revealed as a double
      peak signal. The proportion of double-peak to single-peak signals increased from
      9.3% to 23.0% as nutlin-3 concentration increased. The translocation kinetics of
      the two different MLP conformations with varied applied voltage were analyzed.
      Further, the fractional current of the intra-peak of the double-peak signal was
      analyzed, probing the structure of our designed protein complex. This approach of
      nanopore sensing may be extendedly employed in screening of PPI inhibitors and
      protein conformation studies.

PMID- 30191244
TI  - Measuring the internal quantum yield of upconversion luminescence for ytterbium
      sensitized upconversion phosphors using the ytterbium(iii) emission as an
      internal standard.
AB  - A method is presented for estimating the internal quantum yield (IQY) of NIR-to
      NIR and NIR-to-visible upconversion (UC) luminescence for Yb3+-sensitized energy
      transfer upconversion (ETU) phosphors. The method does not require an integrating
      sphere or a secondary standard, but rather uses the 1 MUm emission of the Yb3+
      sensitizer as an internal standard. The method requires the acquisition of the 1
      MUm emission decay curve of the UC phosphor using low pulse-energy density, an
      estimation of the radiative decay constant of the 1 MUm emission, and emission
      spectra corrected for instrument response. This method is valid for UC emission
      spectra acquired via pulsed or continuous wave (cw) excitation. The method is
      demonstrated for cw excitation to obtain IQY for UC and downshifted luminescence
      for beta-phase NaYF4: 0.5%Tm, 25%Yb and NaYF4: 2%Er, 18%Yb nanocrystals (with and
      without a passivating NaYF4 shell) over a range of excitation irradiance. The
      corresponding results are consistent with those obtained using integrating
      spheres and numerical simulations, respectively. For pulsed excitation, an
      additional alternative method is described which requires acquisition of the 1
      MUm emission decay curve at each excitation pulse-energy density for which the
      IQY is to be determined. The proposed methods should be particularly useful for
      samples having very low absorbance at the excitation wavelength, for which direct
      determination methods are impractical.

PMID- 30191245
TI  - Pressure-induced phase transition, metallization and superconductivity in ZrS2.
AB  - Zirconium disulfide (ZrS2) is an exemplary case among layered materials that
      exhibit unusual electronic and vibrational properties, with applications in
      potential photovoltaic and single-layer transistor materials. Here, we examine
      the effect of pressure on the structural stability, phonon dispersion, electronic
      properties and electron-phonon coupling of ZrS2 using first-principles
      calculations. Our results unravel that ZrS2 undergoes several pressure-induced
      phase transformations from the ambient-pressure P3[combining macron]m1 structure
      to a monoclinic P21/m structure at 2.0 GPa, to an orthorhombic Immm structure at
      5.6 GPa, and to a tetragonal I4/mmm structure at 25.0 GPa. The electronic band
      calculations indicate that the layered P3[combining macron]m1 and P21/m
      structures are narrow-gap semiconductors. The gaps of the above two phases, which
      are normal semiconductors, decrease with pressure. Our results show that ZrS2
      reaches the metallic state by a P21/m -> Immm phase transition and keeps its
      metallic state in the I4/mmm phase. A pressure-driven evolution of the
      topological Fermi surface has been uncovered. The electron-phonon coupling
      results identify superconducting states in both metallic Immm and I4/mmm
      structures. Our research shows that pressure is efficient in the modulation of
      the bonding states, crystal structures and electronic properties of ZrS2, which
      will stimulate further high-pressure structural and conductive measurements.

PMID- 30191246
TI  - Pore-filling contamination in metal-organic frameworks.
AB  - Tuneable pore sizes, ordered crystal structures, and large surface areas are some
      of the main attractive features of metal-organic frameworks (MOFs). To fully
      understand the structure-property relationships of these materials, accurate
      characterisation of their structural features is essential. The surface areas of
      MOFs are routinely estimated from the physical adsorption of gases. By applying
      the Brunauer, Emmett & Teller (BET) theory to an adsorption isotherm, the surface
      area is calculated from the amount of gas that forms a monolayer on the pore
      surface. While this technique is used ubiquitously within the porous solid
      community, its accuracy can be greatly affected by pore-filling contamination.
      This process causes an overestimation of the BET surface area from the overlap of
      surface and pore-filling adsorption as molecules that are not in contact with the
      surface are erroneously included into the surface area calculation.
      Experimentally, it is rather challenging to examine the effects of pore-filling
      contamination, which typically rely on accurate atomistic simulations to provide
      insight. In this work, we employ grand canonical Monte Carlo simulations and
      other theoretical approaches to assess the impact of pore-filling contamination
      on MOF surface areas. With a focus on the rht and nbo topologies, we show how
      experimental studies that suggest MOF surface areas can be increased by replacing
      phenyl rings for alkynes are largely influenced by the pore-filling contamination
      effect.

PMID- 30191247
TI  - Exchange equilibria of carboxylate-terminated ligands at PbS nanocrystal
      surfaces.
AB  - Ligand exchange reactions are commonly used to alter the surface chemistry of
      metal chalcogenide quantum dots; however, a lack of quantifiable data for these
      processes limits the rational functionalization of nanomaterials. Here, we
      quantify the X-type ligand exchange reaction between carboxylate-terminated
      ligands on PbS quantum dots via1H NMR spectroscopy. Using spectroscopic handles
      of both the native and exchange ligand, bound and free forms of each have been
      quantified as a function of exchange ligand concentration. We find that the
      equilibrium constants for the reaction between oleate-capped PbS quantum dots and
      undec-10-enoic acid are 2.23 +/- 0.50 and 2.14 +/- 0.42 for sets of nanocrystals
      prepared by two different synthetic methods. X-ray photoelectron, absorbance, and
      emission spectroscopies indicate that the carboxylate exchange reaction does not
      alter the lead ion coverage of the nanocrystal surface. The quantitative
      equilibrium constant determined herein can be used to improve control over
      partial ligand exchange reactions on PbS nanocrystals.

PMID- 30191248
TI  - Competing roles of interfaces and matrix grain size in the deformation and
      failure of polycrystalline Cu-graphene nanolayered composites under shear
      loading.
AB  - The roles of interfaces and matrix grain size in the deformation and failure of
      polycrystalline Cu-graphene nanolayered (PCuGNL) composites under shear loading
      are explored with molecular dynamics simulations for different repeat layer
      spacings (lambda), Cu grain sizes (D) and graphene chiralities, and an analytical
      model is proposed to describe the shear behavior. At the yield stage, the yield
      stress of the PCuGNL composites is mainly controlled by lambda for lambda <= 15
      nm but mainly by D for lambda > 15 nm; the yield strain of the composites is
      approximately a constant value of 0.056, weakly dependent on lambda, D and
      graphene chirality. The shear failure strain and failure stress are determined
      only by the Cu-graphene interfaces. Small lambda reduces the stability of the
      composites, while large lambda decreases their shear failure strength.
      Considering the yield, failure and interface stability, the optimum lambda value
      for the PCuGNL composites is 2-15 nm. In this optimum lambda range, PCuGNL
      composites can be designed by tailoring Cu-graphene interfaces, regardless of the
      microstructures of polycrystalline Cu.

PMID- 30191249
TI  - Randomized double-blind trial of short- versus long-acting analgesia at the
      sacrospinous ligament.
AB  - INTRODUCTION AND HYPOTHESIS: Pain control is a key component of postoperative
      care; our objective was to evaluate if use of long-acting local anesthesia at the
      sacrospinous ligament leads to decreased postoperative pain versus short-acting
      local anesthesia in patients undergoing sacrospinous ligament fixation. METHODS:
      Women >= 18 years old undergoing sacrospinous ligament fixation to treat pelvic
      organ prolapse were eligible to participate in this randomized trial. Enrolled
      patients were randomized 1:1 to one of two study arms: (1) lidocaine arm (LA) or
      (2) liposomal bupivacaine arm (LBA). Patients in the LA received 30 ml 0.5%
      lidocaine with 1:200,000 epinephrine local injection at the sacrospinous
      ligament. Patients in the LBA received 20 ml 1.3% bupivacaine liposomal mixed
      with 10 ml 0.5% bupivacaine at the sacrospinous ligament. All patients received
      50 ml 0.5% lidocaine with 1:200,000 epinephrine for anterior and/or posterior
      colporrhaphy. The primary outcome of this study was postoperative buttock pain.
      RESULTS: Of the 37 patients enrolled, 33 completed study procedures. Mean age (+/
      SD) was 62.3 years (+/- 11.6) in the LA and 66.8 years (+/- 14.4) in the LBA (p
      = 0.32). All participants underwent sacrospinous ligament fixation; the rate of
      concomitant procedures did not differ between study arms. Visual analog scale
      scores for buttock-specific pain were compared between arms at 1, 3, 6, 12, 24,
      36, 48, 72, 96, and 120 h postoperatively, and no differences were found.
      CONCLUSIONS: Use of long-acting local analgesia at the sacrospinous ligament at
      the time of sacrospinous ligament fixation does not provide any benefit over
      short-acting local analgesia.

PMID- 30191250
TI  - Validation of an educational simulation model for vaginal hysterectomy training:
      a pilot study.
AB  - INTRODUCTION AND HYPOTHESIS: The Miya Model TM (Miyazaki Enterprises, Winston
      Salem, NC, USA) was designed as a realistic vaginal surgery simulation model. Our
      aim was to describe this model and present pilot data on validity and reliability
      of the model as an assessment tool of vaginal hysterectomy skills. METHODS: We
      video recorded ten obstetrics and gynecology residents (novice group) and ten
      practicing gynecologists (expert group) performing vaginal hysterectomy using the
      Miya model. Blood loss and time taken to complete the procedure were documented.
      Participants evaluated the model using a postsimulation survey. In addition, two
      experienced gynecologic surgeons independently evaluated video recordings of each
      participant's performance using two previously validated global rating scales:
      Reznick's Objective Structured Assessment of Technical Skill (OSATS) and Vaginal
      Surgical Skills Index (VSSI). RESULTS: Most participants (80% of novice and 100%
      of expert group) rated the model as effective or highly effective for vaginal
      hysterectomy training and assessment. Median time to procedure completion was
      significantly higher in the novice group, whereas median estimated blood loss was
      no different between groups. No significant differences were observed in the
      composite median OSATS or VSSI scores between groups. The interrater reliability
      indices for subscales and composite scores of the OSATS and VSSI were high and
      ranged from 0.79 to 0.90 and 0.77 to 0.93, respectively. CONCLUSIONS: With
      further study, the Miya Model may be a useful tool for teaching and assessing
      vaginal surgical skills.

PMID- 30191252
TI  - Delivery Assist Catheters : A new Device Class and Initial Experience in
      Mechanical Thrombectomy in Acute Ischemic Stroke Patients.
AB  - PURPOSE: To report in vivo experience of a delivery assist catheter as ascending
      aid for a large-bore catheter for intracranial thromboaspiration. METHODS:
      Retrospective data collection and analysis of stroke databases of two
      comprehensive stroke centers focusing on technical and angiographic parameters -
      primary endpoint defined as reaching the occlusion with a large-bore reperfusion
      catheter - from patients receiving endovascular stroke treatment using an AXS
      OffsetTM delivery assist catheter (Stryker, Fremont, CA, USA) between May 2017
      and November 2017. RESULTS: Using the delivery assist catheter, a 6F catheter
      could be advanced to an intracranial occlusion for direct thromboaspiration in 30
      (88.2%) out of a total of 34 patients (male: n = 14 out of 34 [41.2%], age in
      years: mean [SD]: 75 [11], median baseline NIHSS [National Institutes of Health
      stroke scale]: 16 [interquartile range, IQR 12-21]). In 4 out of 34 (11.7%) cases
      the occlusion could not be reached with the aspiration catheter because of a
      preceding non-occlusive arteriosclerotic plaque (n = 1, 2.9%) or because of
      severe elongation and tortuosity of the arterial access route (n = 3, 8.8%).
      After thromboaspiration mTICI (modified thrombolysis in cerebral infarction) 2b-3
      was reached in 14 out of 30 (46.7%) patients. In 21 out of 34 (61.8%) patients
      stent-retriever-maneuvers (median: 1 [IQR: 0-2]) were needed. In 28 out of 34
      (82.3%) patients final mTICI 2b-3 could be achieved. CONCLUSION: Delivery assist
      catheters can be used as ascending aid for large-bore catheters for
      thromboaspiration in acute ischemic stroke, in particular to overcome vessel
      tortuosity and anatomic obstacles.

PMID- 30191251
TI  - Identification of a locus in maize controlling response to a host-selective toxin
      derived from Cochliobolus heterostrophus, causal agent of southern leaf blight.
AB  - KEY MESSAGE: A host-selective, proteinaceous maize toxin was identified from the
      culture filtrate of the maize pathogen Cochliobolus heterostrophus. A dominant
      gene for toxin susceptibility was identified on maize chromosome 4. A toxic
      activity was identified from the culture filtrate (CF) of the fungus Cochliobolus
      heterostrophus, causal agent of the maize disease southern leaf blight (SLB) with
      differential toxicity on maize lines. Two independent mapping populations; a 113
      line recombinant inbred line population and a 258-line association population,
      were used to map loci associated with sensitivity to the CF at the seedling
      stage. A major QTL on chromosome 4 was identified at the same locus using both
      populations. Mapping in the association population defined a 400 kb region that
      contained the sensitivity locus. By comparing CF-sensitivity of the parents of
      the RIL population with that of the F1 progeny, we determined that the
      sensitivity allele was dominant. No relationship was observed between CF
      sensitivity in seedlings and SLB susceptibility in mature plants; however, a
      significant correlation (- 0.58) was observed between SLB susceptibility and CF
      sensitivity in seedlings. The activity of the CF was light-dependent and was
      sensitive to pronase, indicating that the toxin was proteinaceous.

PMID- 30191253
TI  - [After the reform is before the reform : Results of the amendment processes of
      mental health law in German federal states].
AB  - BACKGROUND: On the basis of mental health law, which differs between the federal
      states in Germany, courts can order the involuntary commitment of people with
      severe mental disorders in psychiatric hospitals, if they present a danger to
      themselves or to others. Due to decisions of the highest courts, these laws have
      been subject to revision since 2011. The aim of this paper is to analyze and
      compare the results of the revision processes in order to define the need for
      action for federal and state legislature. MATERIAL AND METHODS: Research of the
      current status of the revision processes in the federal states and a comparative
      analysis. The state laws were compared on the basis of selected particularly
      relevant areas with respect to human rights and treatment. RESULTS: In spite of
      the revisions the state laws are extremely heterogeneous and in many states do
      not fully comply with the requirements of the United Nations Convention on the
      Rights of Persons with Disabilities (UN-CRPD) or the highest courts' decisions.
      CONCLUSION: The state laws should be harmonized, particularly where they restrict
      basic and human rights, e. g. regarding prerequisites and objectives of
      involuntary commitment and coercive measures.

PMID- 30191255
TI  - Shifts in the Skin-Associated Microbiota of Hatchery-Reared Common Snook
      Centropomus undecimalis During Acclimation to the Wild.
AB  - The skin-associated microbiota of fish competes against pathogens for space and
      nutrients, preventing colonization by harmful bacteria encountered during
      environmental transitions such as those faced during stock enhancement. Thus,
      alterations in bacterial community structure during release of cultured fish have
      important implications for health of these individuals. This study investigated
      microbiota structure during acclimation of juvenile hatchery-reared common snook
      Centropomus undecimalis to the wild by comparing skin-associated microflora among
      snook in captivity, after 48 h of acclimation at release sites, and from the
      wild. After two days of acclimation, the microbiota of hatchery-reared snook
      mirrored that observed on wild snook. Relative abundances of potential pathogens
      were higher in captive fish, whereas acclimated and wild fish harbored bacterial
      taxa influenced by geographical factors and water quality at release sites.
      Predicted microbiota function of acclimated and wild fish showed higher
      production of protective amino acids and antimicrobials, identifying a mechanism
      for microbial supplementation of the immune defense of these fish. The two-day
      transition to wild-type microbiota suggests a temporal scale of hours associated
      with bacterial succession indicating that the microbiota, whose structure is
      vital to fish health, aids in acclimation of fish to new environments during
      stock enhancement efforts.

PMID- 30191257
TI  - Variability in billing practices for whole-body magnetic resonance imaging: reply
      to Degnan et al.

PMID- 30191254
TI  - [Decreased professional performance and quality of life in patients with moderate
      to-severe atopic eczema : Results from the German atopic eczema registry
      TREATgermany].
AB  - BACKGROUND: Clinical registries may provide high-quality evidence on the use and
      effectiveness of therapeutic interventions under real-life conditions. Adults
      with moderate-to-severe atopic eczema (atopic dermatitis [AD]) are enrolled into
      TREATgermany and prospectively followed over at least 2 years. This paper
      analyses the association between dermatological quality of life and work
      limitations. MATERIALS AND METHODS: Treatment modalities and a broad set of
      physician- and patient-reported outcome measures are documented using validated
      instruments to assess clinical disease severity (EASI [Eczema Area and Severity
      Index], objective SCORAD [objective-SCORing Atopic Dermatitis]), quality of life
      (DLQI [Dermatology Life Quality Index]), symptoms (POEM [Patient-oriented Eczema
      Measure]), global disease severity, as well as patient satisfaction and work
      limitations including presenteeism (WLQ [Work Limitation Questionnaire]). From
      06/2016 until 12/2017, 241 individuals (mean age 43 +/- 15 years, 38.6% female)
      were enrolled at 19 recruitment centers; 69% of the patients were employed.
      RESULTS: Employed persons had DLQI and WLQ scores of 10.6 +/- 6.9 points and 17.7
      +/- 18.1%, respectively. Mean presenteeism was substantial accounting for 9.2%.
      With coefficients of 0.39 and 0.33 WLQ and presenteeism scores significantly
      correlate with DLQI (p < 0.000). Bootstrapped regression models showed that the
      limitations in coping with work requirements increase by 1.7% as DLQI increases
      by one point. Lower quality of life due to AD is most strongly associated with
      limitations in the area of physical and performance requirements in general.
      Presenteeism increases by 0.5% as DLQI increases by one point. CONCLUSION:
      Moderate-to-severe AD has substantial adverse economic impact with mean
      productivity loss of patients of almost 10%. Future analyses from TREATgermany
      will address the impact of innovative treatment modalities on quality of life and
      work productivity of patients with moderate-to-severe AD.

PMID- 30191256
TI  - Management of metastatic melanoma: improved survival in a national cohort
      following the approvals of checkpoint blockade immunotherapies and targeted
      therapies.
AB  - BACKGROUND: Immune checkpoint blockade (ICB) and BRAFV600-targeted therapy have
      demonstrated substantial clinical efficacy for patients with stage 4 melanoma in
      clinical trials; however, their impact on survival and barriers to treatment in
      the "real-life" setting remains unknown. METHODS: Patients who presented with
      cutaneous melanoma during 2004-2015 using the National Cancer Database, which
      comprises > 70% of all newly diagnosed cancers in the U.S., were evaluated for
      predictors of presenting with stage 4 disease and receiving ICB, and for their
      associated unadjusted and risk-adjusted overall survival (OS). RESULTS: 17,975
      patients presented with stage 4 metastatic cutaneous melanoma. Overall, patients
      who presented after the FDA's initial approvals (starting in 2011) for ICB and
      BRAFV600-targeted therapy demonstrated a 31% relative improvement in 4-year OS (p
      < 0.001), compared to pre-2011. Following the initial approvals in 2011, improved
      OS was associated in risk-adjusted analyses with ICB (HR 0.57, 95CI 0.52-0.63).
      ICB demonstrated improved median and 4-year OS of 16.9 months (95CI 15.6-19.3;
      vs. 7.7 months, 95CI 7.2-8.4) and 32.4% (95CI 29.5-35.3; vs. 21.0%, 95CI 19.6
      22.2, all p < 0.001), respectively; improved OS was persistent in unadjusted and
      risk-adjusted landmark survival analyses. Uninsured patients and management in
      the community setting were less likely to receive ICB in multivariable analyses.
      CONCLUSIONS: In a national "real-life" treatment population, we show that the
      wide availability of the novel treatment modalities ICB and BRAFV600-targeted
      therapy has significantly improved the survival of patients with stage 4
      melanoma. Our findings additionally suggest that there are opportunities for
      expanding coverage and access to these novel immunotherapies in community
      practice.

PMID- 30191259
TI  - Analysis of neurotransmitter levels in addiction-related brain regions during
      synthetic cathinone self-administration in male Sprague-Dawley rats.
AB  - RATIONALE: Synthetic cathinones are used as stimulants of abuse. Different
      stimulants may induce distinct rates of disease progression, yielding
      neurochemical changes that may vary across brain regions or neurotransmitter
      systems. OBJECTIVES: This research sought to behaviorally and chemically
      differentiate stages of synthetic cathinone abuse through rodent self
      administration and measurement of the neurotransmitter profile in multiple brain
      regions. METHODS: Male rats were trained to self-administer alpha-PVP, mephedrone
      (4MMC), or saline. Half of each drug group stopped self-administering after
      autoshaping; the other half self-administered for another 21 days. Brain tissue
      from amygdala, hippocampus, hypothalamus, PFC, striatum, and thalamus was
      profiled with electrochemical detection to assess neurotransmitter levels.
      RESULTS: During autoshaping, the majority of infusions were delivered
      noncontingently. In the self-administration phase, rats responded more for alpha
      PVP and 4MMC than for saline, demonstrating that both synthetic cathinones were
      reinforcing. Longer durations of exposure elevated 5-HIAA in hypothalamus, PFC,
      and hippocampus, indicating that learning may produce changes in addiction
      related brain regions. Both synthetic cathinones decreased norepinephrine in
      hippocampus, while alpha-PVP decreased glutamate in hippocampus and PFC, and 4MMC
      decreased glutamate in thalamus. Furthermore, alpha-PVP increased dopaminergic
      metabolites in striatum, whereas 4MMC decreased serotonin in the amygdala,
      hippocampus, and PFC. Interestingly, neither synthetic cathinone affected
      dopamine levels despite their functional effects on the dopaminergic system.
      CONCLUSIONS: In summary, the neurotransmitter changes observed here suggest that
      synthetic cathinone use likely produces sequential neurochemical changes during
      the transition from use to abuse. Consequently, treatment need may differ
      depending on the progression of synthetic cathinone abuse.

PMID- 30191258
TI  - Incorporating the patient perspective in the study of rare bone disease: insights
      from the osteogenesis imperfecta community.
AB  - : There is limited research which examines health concerns of individuals with
      osteogenesis imperfecta (OI). Discussion groups with leaders of the adult OI
      community identified a broad range of medical priorities beyond fractures and
      brittle bones. Our work underscores the need to include patient-reported outcomes
      in rare bone disease research. INTRODUCTION: Osteogenesis imperfecta (OI) is a
      rare genetic disorder affecting collagen protein leading to brittle bones and a
      number of other medical complications. To date, there is limited research which
      examines the life-long process of aging with this rare disease, much less the
      perspective of individuals with OI. METHODS: In order to explore and prioritize
      health concerns that adults with OI feel have been inadequately addressed in
      health care and research, investigators held discussions with leaders from the
      global adult OI community. The meetings were held in August 2017 at the 13th
      International Conference on OI in Oslo, Norway as part of the preconference
      seminar "Patient Participation in OI Research". Investigators were part of the
      Brittle Bone Disease Consortium (BBDC), a multicenter research program devoted to
      the study of OI, and their focus was on patient-reported outcomes (PRO). RESULTS:
      Participants noted that while fractures and brittle bones are the most common
      feature of OI, a number of body systems are under-studied in this disorder. They
      particularly emphasized breathing, hearing, and the effects of aging as primary
      concerns that researchers and physicians may not fully understand or address.
      Other areas included pain, gastrointestinal problems, mental health, nutrition,
      menopause/pregnancy, and basilar invagination. Participants also emphasized that
      they must be informed of study results. They underscored that outcome measures
      incorporated into future drug trials must look beyond fractures and consider the
      whole patient. CONCLUSIONS: This work will help guide the incorporation of PROs
      into the next phase of the BBDC Natural History Study of OI and underscores the
      importance of including PROs in the study of rare diseases.

PMID- 30191260
TI  - The role of bone SPECT/CT in patients with persistent or recurrent lumbar pain
      following lumbar spine stabilization surgery.
AB  - PURPOSE: Despite recent advances in lumbar spine stabilization surgery (LSSS), a
      high number of patients continue to complain of persistent/recurrent lumbar pain
      after LSSS. Conventional imaging (plain radiography, CT and MRI) is commonly
      performed to assess potential lumbar pain generators, but findings are equivocal
      in approximately 20% of patients. The purpose of this study was to assess the
      diagnostic performance of 99mTc-HDP bone SPECT/CT in identifying potential pain
      generators in patients with persistent/recurrent lumbar pain after LSSS but in
      whom conventional diagnostic imaging is inconclusive. METHODS: A total of 187
      patients (median age 56 years, 70 men) with persistent/recurrent lumbar pain
      following LSSS with inconclusive conventional imaging (plain radiography, CT
      and/or MRI) underwent 99mTc-HDP bone SPECT/CT and were included in the study.
      Tracer uptake on SPECT/CT, as an indicator of ongoing or altered osteoblastic
      activity, was assessed in the lumbar spine stabilization segment(s) and in
      adjacent segments. Uptake intensity was graded as (1) high (the same as or more
      than iliac crest uptake), (2) mild (the same as or more than nondiseased
      vertebral uptake but less than iliac crest uptake), or (3) negative (normal
      scan). Mild and high uptake were regarded as positive. RESULTS: In 160 of the 187
      patients (85.6%), SPECT/CT showed positive mild or high tracer uptake in the LSSS
      region. More than half of the patients had abnormal tracer uptake in the
      stabilized segments (56.7%) and/or in the adjacent segments (55.6%). Although
      positive stabilized segment findings were commonly seen at <2 years (70.3%) and
      the rate decreased with time after LSSS, they were seen at >6 years after surgery
      in 38.2% of patients. In 51.4% of patients, abnormal activity was seen in the
      adjacent segments <2 years after LSSS, suggesting early/accelerated degeneration
      after surgery. The proportion of patients with abnormal activity in the adjacent
      segments increased to 67.3% at >6 years after LSSS (p < 0.05). Positive SPECT/CT
      findings in the stabilized segments were more frequent in patients with three or
      more stabilized segments (p < 0.05), but were not more frequent in the adjacent
      segments. Overall, positive SPECT/CT guided therapy in 64% of patients, which
      included facet joint/nerve root injections or re-do surgery at active sites
      and/or adjacent sites. CONCLUSION: Bone SPECT/CT is a sensitive diagnostic tool
      for identifying altered osteoblastic activity, which might be a pain generator in
      patients with persistent/recurrent pain after lumbar surgery especially when
      conventional imaging is inconclusive.

PMID- 30191261
TI  - Adaptation to visual feedback delays on touchscreens with hand vision.
AB  - Direct touch finger interaction on a smartphone or a tablet is now ubiquitous.
      However, the latency inherent in digital computation produces an average feedback
      delay of ~ 75 ms between the action of the hand and its visible effect on digital
      content. This delay has been shown to affect users' performance, but it is
      unclear whether users adapt to this delay and whether it influences skill
      learning. Previous work studied adaptation to feedback delays but only for longer
      delays, with hidden hand or indirect devices. This paper addresses adaptation to
      touchscreen delay in two empirical studies involving the tracking of a target
      moving along an elliptical path. Participants were trained for the task either at
      the minimal delay the system allows (~ 9 ms) or at a longer delay equivalent to
      commercialized touch devices latencies (75 ms). After 10 training sessions over a
      minimum of 2 weeks (Experiment 1), participants adapt to the delay. They also
      display long-term retention 7 weeks after the last training session. This
      adaptation generalizes to a similar tracking path (e.g., infinity symbol). We
      also observed generalization of learning from the longer delay to the minimal
      delay condition (Experiment 2). The delay thus does not prevent the learning of
      tracking skill, which suggests that delay adaptation and tracking skill could be
      two separate components of learning.

PMID- 30191262
TI  - The effect of laquinimod, a novel immuno-modulator in development to treat
      Huntington disease, on the pharmacokinetics of ethinylestradiol and
      levonorgestrel in healthy young women.
AB  - PURPOSE: Laquinimod is an orally dosed immuno-modulator currently under
      development for Huntington's disease (HD). Preclinical findings suggest potential
      teratogenicity of laquinimod, thus the reproductive ability of females with HD
      treated with laquinimod needs to be closely managed. Because combined oral
      contraceptives (COC) are often used in this context, the pharmacokinetics of COC
      containing ethinylestradiol (EE) and levonorgestrel (LNG) in combination with
      laquinimod (0.6 mg/day) was evaluated. METHODS: In this randomized, phase-1
      single-center, double-blind, placebo-controlled, 2-way crossover drug-drug
      interaction (DDI) study in 48 healthy premenopausal women, COC were administered
      in a 28-day regimen of 21 days followed by 7 pill-free days for 4 cycles and
      laquinimod or placebo was administered for 28 days in cycle 1 and cycle 3
      starting 7 days prior to COC administration. Blood samples for pharmacokinetic
      profiling of laquinimod, EE and LNG were collected on day 21 and day 22 of Cycles
      1 and 3 pre-dose and multiple times post-dose. RESULTS: The ratio of geometric
      means and 90% confidence intervals for AUC0-24 and Cmax of EE and LNG with and
      without laquinimod were all within the bioequivalence range (80 to 125%).
      Laquinimod pharmacokinetics was consistent with those observed in previous
      studies. The adverse event profile was in line with the current knowledge on the
      safety profile of both drugs, with headache as the most frequently reported
      treatment-related adverse event. CONCLUSION: The combination of COC and
      laquinimod treatment was found to be safe, tolerable, and devoid of any
      noticeable pharmacokinetic interaction.

PMID- 30191263
TI  - Health-related quality of life in adult heart-transplant recipients-a systematic
      review.
AB  - BACKGROUND: Health-related quality of life is a multidimensional concept to
      assess the impact of medical interventions from an individual perspective. This
      concept is important to evaluate benefits of heart transplantation. This
      systematic review was conducted to determine (1) posttransplant health-related
      quality of life in heart transplantation patients and (2) influencing factors of
      health-related quality of life. METHODS: A systematic review of cross-sectional,
      prospective and mixed methods studies published from November 2007 to November
      2017 was conducted on PsycINFO, PSYNDEX and PubMed using a combination of the
      keywords heart transplantation, heart transplantation patient, quality of life,
      and health-related quality of life. RESULTS: A total of 14 studies with a cross
      sectional design, 6 studies with a prospective design and 2 mixed-methods studies
      were identified. The stability of health-related quality of life up to 10 years
      after transplantation has been reported. Most often generic scales, such as SF-36
      (8) and WHOQoL-BREF (7) were used for data collection. Demoralization,
      depression, pain, gastrointestinal symptoms, sexual dysfunction, and poor oral
      health influence health-related quality of life negatively, whereas social and
      family support have a positive impact. CONCLUSION: Although health-related
      quality of life is positively influenced by transplantation, further research
      regarding gender differences is needed. Disease-specific scales were rarely used.

PMID- 30191264
TI  - Optical coherence tomography-verified longer balloon inflation time may provide
      better stent apposition and optimal index parameters.
AB  - BACKGROUND: Incomplete stent expansion and inadequate apposition predispose to
      stent thrombosis following percutaneous coronary intervention. Recent studies
      have shown that increasing the duration of balloon inflation during stent
      employment was beneficial. Thus, the balloon inflation time required for optimal
      stent expansion and apposition in patients receiving second-generation drug
      eluting stents (DES) were determined using optical coherence tomography (OCT).
      PATIENTS AND METHODS: Between April 2014 and March 2015, 38 patients (28 men, 10
      women; mean age 60.5 +/- 11.4 years) with stable angina pectoris due to single
      significant de novo coronary artery stenosis were prospectively enrolled. All
      patients were administered aspirin and clopidogrel and received weight-adjusted
      intravenous unfractionated heparin. Images of basal lesions were obtained using
      the C7XR LightLab Dragonfly OCT catheter. RESULTS: Expansion and apposition
      parameters improved with increasing duration of balloon inflation (30 s or 60 s)
      with nominal pressure (12 atm). Mean lesion length was 19.8 +/- 7.6 mm. Mean
      stent diameter and length were 2.8 +/- 0.36 mm and 24.9 +/- 7.6 mm, respectively.
      CONCLUSION: With deployment of a stent at nominal pressure with conventional
      duration, inadequate stent expansion and malapposition frequently occurred as
      detected by OCT; however, a balloon inflation duration of 60 s markedly improved
      stent expansion and apposition parameters without significant complications.

PMID- 30191265
TI  - Cardiac rehabilitation therapy for coronary slow flow phenomenon.
AB  - OBJECTIVE: To evaluate the effectiveness of cardiac rehabilitation on coronary
      slow flow phenomenon. METHOD: Included were 30 consecutive patients from June
      2015 to June 2017. A thrombolysis in myocardial infarction (TIMI) frame
      evaluation was used to estimate coronary blood flow velocity. All coronary
      angiography diameters were normal, but blood flow levels did not reach the TIMI
      level 3. All patients were treated with aspirin and rosuvastatin. Patients were
      randomly assigned to an experimental group (cardiac rehabilitation treatment
      group, n = 15) or a control group (normal treatment without cardiac
      rehabilitation, n = 15). Plasma low density lipoprotein cholesterol (LDL-C),
      triglyceride (TG), high-sensitivity C reactive protein (hs-CRP), homocysteine
      (Hcy) and arginine (Arg) expression levels were collected after admission. These
      indices were reviewed again after 20-30 weeks, improved subjective symptoms were
      evaluated by multiple outcome criteria (MOCs), and coronary angiography was used
      to evaluate the velocity of coronary artery blood flow. RESULT: The expression
      levels of LDL-C and TG in the experimental group were significantly lower than
      those of the control group (both P < 0.01). The plasma levels of hs-CRP, Hcy and
      Arg were lower than those in the control group (all P < 0.01). In the
      experimental group, subjective symptoms of chest pain were significantly improved
      and the coronary artery blood flow velocity was significantly increased compared
      with the control group (P < 0.01). CONCLUSION: Cardiac rehabilitation can reduce
      the plasma levels of LDL-C, TG, hs-CRP, Hcy and Arg, significantly improve the
      symptoms of coronary slow flow phenomenon and accelerate the speed of coronary
      artery blood flow.

PMID- 30191266
TI  - ?

PMID- 30191267
TI  - [Is the school entrance examination a door opener for health sciences research? :
      Analyzing study participation of hard-to-reach groups].
AB  - BACKGROUND: Additional scientific surveys within the compulsory school entrance
      examination (SEE) have become increasingly popular, partly because the SEE
      potentially reaches all socioeconomic groups. However, it has not been
      sufficiently explored whether selective participation in voluntary supplementary
      surveys actually results in no selection bias along socioeconomic
      characteristics. Therefore, the aim of this study is to analyze the participation
      of potentially hard-to-reach families in a parent survey at the SEE. MATERIALS
      AND METHODS: The parent survey on the utilization of community prevention has
      been linked to the SEE in a community in North Rhine-Westphalia. We compared
      families with low and higher education (CASMIN classification), families with and
      without migration background (at least one parent was not born in Germany), as
      well as single-parent and two-parent families. Using logistic regression we
      analyzed whether survey participation (n = 3410) and non-participation (n = 346)
      was different along all three indicators. RESULTS: Families with low education
      were slightly more often among the group of participants compared to non
      participants (11.2 vs. 8.8%; odds ratio (OR) 1.29; 95% confidence interval (CI)
      0.85-1.95) and single-parent families slightly less often (14.1 vs. 17.7%; OR
      0.75; 95% CI 0.55-1.02). Families with migration background participated
      significantly more often (52.9 vs. 46.1%; OR 1.27; 95% CI 1.01-1.60).
      CONCLUSIONS: Hard-to-reach families could be recruited for a voluntary parent
      survey in the SEE to a satisfying degree. This illustrates the potential of the
      SEE for population-based basic and evaluation research.

PMID- 30191269
TI  - [Family-oriented health promotion : A user-oriented approach for health promotion
      with children and families in municipalities].
AB  - Community health promotion with children requires a conceptual framework to
      support children and families and sustainably improve their health
      opportunities.Family-oriented health promotion is an approach to implement this
      demanding task. It focuses in particular on the user perspective of families. It
      can be conceptually presented along the life-stage approach. Pregnancy, early
      childhood and adolescence as well as transitions between age-specific
      socialization institutions are highly vulnerable. Additionally, burdened life
      situations are presented along familial adversities such as poverty, isolation,
      single parenting, external placement or illnesses, and life-specific approaches
      to health promotion and prevention are named. Family-oriented health promotion
      should avoid stigmatization and support families through municipalities and other
      settings.

PMID- 30191270
TI  - [Hospitalizations and amputations for diabetes mellitus-trends and small-area
      variation in Germany].
AB  - BACKGROUND: Hospitalizations and lower limb amputations related to diabetes
      mellitus (DM) are considered to be potentially avoidable. Appropriate outpatient
      care of diabetes prevents complications. Rates on potentially avoidable
      hospitalizations for diabetes are core indicators of the German diabetes
      surveillance program. International comparisons showed high hospitalization rates
      in Germany for both indicators. OBJECTIVES: The objective of this analysis is to
      describe time trends on hospitalizations and inpatient lower limb amputations
      (major amputations) for DM. Furthermore, we analyze small area variations.
      MATERIALS AND METHODS: Based on the German diagnosis related groups (DRGs)
      dataset we calculated age-standardized rates covering 2005-2015. Calculations
      rely on the Organisation for Economic Co-operation and Development (OECD)
      indicator definitions. Time trends are obtained by linear regression modelling.
      We also stratified into age groups and analyzed 2015 small-area variations using
      age-adjusted rates. RESULTS: Crude hospitalization rates were 310 admissions per
      100,000 inhabitants in men (amputation rate: 15.6) and 216 admissions per 100,000
      inhabitants in women (amputation rate: 7.1) in 2015. Age-adjusted
      hospitalizations and amputations rates in women decreased over time (10.3 and 1.2
      cases per 100,000 inhabitants and year, respectively). In men, the amputation
      rate decreased significantly (1.5 cases per 100,000 inhabitants and year). We
      found higher rates for men than for women in almost all age categories. In
      eastern Germany and parts of Bavaria and North Rhine-Westphalia rates are
      particularly high. CONCLUSIONS: A decrease in hospitalization rates may indicate
      improvements in ambulatory diabetes care over time. Future studies should
      consider age-specific differences and small-area variations.

PMID- 30191268
TI  - National public health system responses to diabetes and other important
      noncommunicable diseases : Background, goals, and results of an international
      workshop at the Robert Koch Institute.
AB  - Diabetes mellitus and other noncommunicable diseases (NCDs) represent an emerging
      global public health challenge. In Germany, about 6.7 million adults are affected
      by diabetes according to national health surveys, including 1.3 million with
      undiagnosed diabetes. Complications of diabetes result in an increasing burden
      for individuals and society as well as enormous costs for the health care system.
      In response, the Federal Ministry of Health commissioned the Robert Koch
      Institute (RKI) to implement a diabetes surveillance system and the Federal
      Center for Health Education (BZgA) to develop a diabetes prevention strategy. In
      a two-day workshop jointly organized by the RKI and the BZgA, representatives
      from public health institutes in seven countries shared their expertise and
      knowledge on diabetes prevention and surveillance. Day one focused on NCD
      surveillance systems and emphasized both the strengthening of sustainable data
      sources and the timely and targeted dissemination of results using innovative
      formats. The second day focused on diabetes prevention strategies and highlighted
      the importance of involving all relevant stakeholders in the development process
      to facilitate its acceptance and implementation. Furthermore, the effective
      translation of prevention measures into real-world settings requires data from
      surveillance systems to identify high-risk groups and evaluate the effect of
      measures at the population level based on analyses of time trends in risk factors
      and disease outcomes. Overall, the workshop highlighted the close link between
      diabetes prevention strategies and surveillance systems. It was generally stated
      that only robust data enables effective prevention measures to encounter the
      increasing burden from diabetes and other NCDs.

PMID- 30191271
TI  - [Growing up mentally healthy : A question of origin, social participation
      opportunities or utilisation of community-based health promotion?]
AB  - This article addresses the question of children's mental health in the context of
      ethnic origin, different socioeconomic resources of the families and the
      utilisation of local health promotion. Collected data from the project "Gesund
      Aufwachsen" (Growing up healthy) were used for this contribution. Data of
      children of preschool and school age, parents and educational professionals from
      11 facilities were evaluated. Quantitative results are reported in aspects of
      resilience and strengths and difficulties of children. Results show that children
      with a migration background hardly differ from children without a migration
      background. Merely minor differences between school classes and gender could be
      identified. Also, with regards to socioeconomic characteristics, such as
      educational status, income and receiving governmental benefits, the coherences
      regarding the healthy mental development of children were lower than expected. In
      reference to community-based health opportunities it was clear that these were
      mostly utilised by parents who were not the primary target group of such offers.

PMID- 30191272
TI  - ?

PMID- 30191273
TI  - Microextraction combined with microderivatization for drug monitoring and protein
      modification analysis from limited blood volume using mass spectrometry.
AB  - In the clinic, ethosuximide is commonly used to treat generalized absence
      seizures but has recently been repurposed for other diseases. Because of adverse
      effects and drug interactions, high-throughput therapeutic drug monitoring of
      ethosuximide is necessary. Microextraction is a simple, effective, rapid, and low
      consumption of organic solvents method for sample preparation. In this study,
      microderivatization-increased detection (MDID)-combined microextraction was used
      to detect ethosuximide by mass spectrometry. Ethosuximide is a difficult to
      retain and ionize compound in the C18 nano-flow column and ionization interface,
      respectively. Hence, we developed a fast method for detecting ethosuximide in
      human plasma by using the MDID strategy (within 2 min). Chemical
      microderivatization parameters were studied and optimized to increase the
      sensitivity of ethosuximide detection at trace levels. The linear range for the
      analysis of ethosuximide in 10 MUL plasma was 5-500 MUg/mL with a coefficient of
      determination (r2) >= 0.995. The precision and accuracy of intraday and interday
      analyses of ethosuximide were below 13.0%. Furthermore, modifications of major
      proteins in plasma and blood cells, induced by ethosuximide, were identified. The
      proposed method effectively utilizes microliter samples to detect drug plasma
      concentrations under suitable microextraction procedures toward the eco-friendly
      goal of low consumption of organic solvents. Graphical abstract ?.

PMID- 30191275
TI  - Multiplex PCR Unyvero i60 ITI application improves detection of low-virulent
      microorganisms in periprosthetic joint infections.
AB  - PURPOSE: The aim of this study was to evaluate the pre-operative performance of
      an automated multiplex PCR (mPCR) system in patients with suspected
      periprosthetic joint infection (PJI). METHODS: Under sterile conditions, synovial
      fluid samples from patients with a suspected PJI were collected pre-operatively.
      One hundred eighty microliter of the aspirate was used for analysis in the mPCR.
      The remaining joint fluid was sent for microbiological analysis. PJI was
      diagnosed by using the Musculoskeletal Infection Society (MSIS) criteria. Total
      percentage agreement and Cohen's kappa coefficient were calculated to measure
      overall agreement. RESULTS: Overall, 90 patients with a suspected PJI were
      included. Using MSIS criteria, 38 (42%) patients were classified as septic. Total
      percent agreement between mPCR and synovial fluid culture was 86% with a Cohen's
      kappa of 0.68. The mPCR and synovial fluid culture showed sensitivities of 71%
      and 84%, respectively. Combined evaluation provided an even higher sensitivity of
      92%. While Cutibacterium spp. were detected five times by mPCR, it could only be
      cultured once. A higher detection rate of CoNS by mPCR (n = 7) compared to
      conventional culture (n = 5) was also demonstrated. In comparison to synovial
      fluid culture, the mPCR missed Staphylococcus aureus five times. CONCLUSION: With
      a moderate agreement between synovial fluid mPCR and culture, the mPCR system
      could be a useful adjunct in diagnosing a PJI pre-operatively. Due to faster
      availability of results and a higher detection rate of low-virulent
      microorganisms, it can complement conventional culture.

PMID- 30191274
TI  - Turn-on fluorescent detection of captopril in urine samples based on hydrophilic
      hydroxypropyl beta-cyclodextrin polymer.
AB  - Here, one kind of hydrophilic hydroxypropyl beta-cyclodextrin cross-linked
      polymer (HP-CDP) was prepared and used to establish a "turn-on" fluorescent probe
      for selective determination of captopril in biological samples. The HP-CDP has
      been synthesized in one step by cross-linking (2-hydroxypropyl)-beta-cyclodextrin
      (HP-beta-CD) with a rigid aromatic group linker tetrafluoroterephthalonitrile
      (TFT), and the synthesis parameters of HP-CDP were optimized with water
      solubility, yield, and adsorption capacity as indicators. When it was used as a
      luminescent material, we have found an interesting phenomenon that the
      fluorescence emission of HP-CDP was quenched after forming a coordination
      compound with ferric ions, and then recovered after adding a certain
      concentration of captopril, since captopril can reduce the ferric iron to ferrous
      ions and cause ligand replacement. Based on this observation, a novel turn-on
      fluorescent method was developed for the determination of captopril. The method
      exhibited good linearity in the range of 9.2 * 10-7 to 4.6 * 10-4 M (R2 = 0.9982)
      and a low detection limit of 1.8 * 10-7 M at optimum HP-CDP concentration, ferric
      ion concentration, pH, and incubation time. Moreover, interference experiments
      demonstrated that this fluorescence sensor had excellent selectivity that can
      commendably resist the interference from potential foreign substances. The
      proposed method has been successfully applied to determine captopril in human
      urine samples and may provide outstanding application potential in the future
      development of sensors. In addition, it is believed that HP-CDP also has a wide
      range of applications, for example, as a solubilizer, pollutant adsorbent, or
      drug carrier. Graphical abstract ?.

PMID- 30191276
TI  - Standards for external fixation application: national survey under the auspices
      of the German Trauma Society.
AB  - INTRODUCTION: External fixation is widely accepted as a provisional or sometimes
      definitive treatment for long-bone fractures. Indications include but are not
      limited to damage control surgery in poly-traumatized patients as well as
      provisional bridging to definite treatment with soft tissue at risk. As little is
      known about surgeon's habits in applying this treatment strategy, we performed a
      national survey. METHODS: We utilized the member database of the German Trauma
      Society (DGU). The questionnaire encompassed 15 questions that addresses topics
      including participants' position, experience, workplace, and questions regarding
      specifics of external fixation application in different anatomical regions.
      Furthermore, we compared differences between trauma centre levels and surgeon
      related factors. RESULTS: The participants predominantly worked in level 1 trauma
      centres (42.7%) and were employed as attendings (54.7%). There was widespread
      consensus for planning and intra-operative radiographical control of external
      fixation. Surgeons appointed at a level I trauma centre preferred significantly
      more often supra-acetabular pin placement in external fixation of the pelvis
      rather than the utilization of iliac pins (75.8%, p = 0.0001). Moreover, they
      were more likely to favor a mini-open approach to insert humeral pins (42.4%, p =
      0.003). Overall, blunt dissection and mini-open approaches seemed equally popular
      (38.2 and 34.1%). Department chairmen indicated more often than their colleagues
      to follow written pin-care protocols for minimization of infection (16.7%, p =
      0.003). CONCLUSION: Despite the fact that external fixation usage is widespread
      and well established among trauma surgeons in Germany, there are substantial
      differences in the method of application.

PMID- 30191277
TI  - Fading lemonade challenge.

PMID- 30191278
TI  - Solution to best food reference material challenge.

PMID- 30191280
TI  - Opinions on the "Trick" Technique to Reposition the NAC in Female-to-Male
      Transsexuals.

PMID- 30191279
TI  - Clinical Impact of Highly Condensed Stromal Vascular Fraction Injection in
      Surgical Management of Depressed and Contracted Scars.
AB  - BACKGROUND: Recent research on stromal vascular fraction (SVF) has demonstrated
      the presence of numerous growth factors that aid in tissue regeneration and
      suggest the potential for scar treatment. This study was conducted to clinically
      show that adding stem cells can improve the surgical outcomes of scar formation.
      METHODS: Between March 2014 and February 2016, 17 patients underwent injections
      of fat and highly condensed SVF simultaneously with scar reduction surgeries and
      15 patients received scar revision with or without simultaneous application of
      highly condensed SVF (4.90 * 107 stem cells/ml) at our institution. Clinical
      photographs were taken before and after surgery, and the scars were graded using
      the following standard scales: the Observer Scar Assessment Scale (OSAS), Stony
      Brook Scar Evaluation Scale (SBSES), Vancouver Scar Scale (VSS), and Visual
      Analog Scale (VAS). RESULTS: All patients showed improvement, registering
      significant increases in scar tissue scores (P < 0.05 in all four scoring
      systems). Patients in the SVF group showed more improved outcomes than patients
      in the non-SVF group for all scar tissue scores except the SBSES (OSAS, P =
      0.029; SBSES, P = 0.281; VSS, P = 0.001; VAS, P = 0.021). Subcategories of these
      scales reflected more favorable outcomes in terms of height and pliability;
      however, there was no significant change in vascularity. CONCLUSIONS: SVF
      injections enhance tissue regeneration by contributing stem cells and growth
      factors to improve outcomes in scar revisions or tissue grafts. Harvesting the
      SVF through liposuction also provides a cosmetic benefit. Significant SVF-related
      gains in the scoring of scars indicate the merit of SVF as an aspect of
      conventional scar management. 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- 30191281
TI  - Orbicularis-Tarsus Fixation Approach in Double-Eyelid Blepharoplasty: A
      Modification of Park's Technique.
AB  - BACKGROUND: Incisional double-eyelid blepharoplasty is widely applied because of
      its extensive indications and robust results. The orbicularis-levator fixation
      method is an incisional approach that provides stronger adhesion than traditional
      techniques. However, there remains the risk of postoperative relapse or suture
      spitting out. METHODS: The authors introduced a modified technique for
      supratarsal crease formation. When necessary soft tissue removal was completed,
      the orbicularis oculi muscle was anchored on the tarsus. Then the muscle edges
      near canthus were reattached to prevent muscle retraction. For skin closure, the
      skin-pretarsal fascia-skin maneuver was adopted to enhance cicatricial adhesion.
      RESULTS: Six hundred and fifty-nine patients underwent double eyelidplasty by the
      same surgeon using this modified technique. Patients were followed up from 2 to
      38 months, with a mean period of 15 months. Short-term complications included
      mild edema, bruising or reddish change of the upper eyelid, yet all gradually
      relieved in 6-8 weeks. Fourteen cases of palpebral fold asymmetry and nine cases
      of unsatisfactory fold formation near the inner canthus were encountered, and all
      the defects had been well improved by revision surgeries. Ninety-five percent of
      the patients were satisfied with the long-term outcomes, which showed as natural
      and well-defined palpebral folds without scar hypertrophy, suture spitting out or
      crease depression. Besides, no supratarsal crease drooping or disappearing was
      observed 3 years postoperatively. CONCLUSIONS: The authors introduced an
      orbicularis-tarsus fixation method for upper eyelid blepharoplasty. It is a
      reliable technique that enables high feasibility and long-lasting result, and
      with lower risk of suture spitting out. 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- 30191282
TI  - Irp2 Knockout Causes Osteoporosis by Inhibition of Bone Remodeling.
AB  - It has been found that iron disorder may lead to osteoporosis. However, the
      mechanism has been little explored. In the present study, we try to investigate
      the effects of iron disorder on bone metabolism using Irp2 knockout (Irp2-/-)
      mice. Female Irp2-/- mice were used in this study. Bone mineral density (BMD) was
      measured by Micro-CT. Serum markers for bone turnover were measured by enzyme
      linked immunosorbent assay. Content of iron was measured in bone and liver
      tissue, and Vitamin D 25-hydroxylase (CYP2R1) content was measured in liver
      tissue. Relative gene expression involved in iron export and uptake, and some
      genes involved in activities of osteoblast and osteoclast were all measured by
      real-time PCR and western blot. Compared to wild-type mice, Irp2-/- mice
      exhibited reduced BMD, bone iron deficiency, and hepatic iron overload. Serum
      levels of 25(OH)D3 and markers for bone formation such as bone alkaline
      phosphatase (Balp), bone-gla-protein (BGP), and type I collagen alpha1 chain (Col
      I alpha1) were decreased, while markers for bone resorption including cathepsin K
      (Ctsk) and tartrate-resistant acid phosphatase (Trap) were all significantly
      increased. Hepatic CYP2R1 level was decreased in Irp2-/- mice compared with wild
      type control mice. Compared to wild-type C57BL6 control mice, the expression of
      genes involved in osteoblast activity such as Balp, BGP, and Col I alpha1 were
      all significantly decreased in bone tissue, while genes for osteoclast activity
      such as Ctsk and Trap were all markedly increased in Irp2-/- mice at mRNA level.
      Genes involved in iron storage, uptake, and exporting were also measured in bone
      tissue. Posttranscriptionally decreased ferritin (FTL), ferroportin 1 (FPN1), and
      increased transferrin receptor 1 (TfR1) gene expressions have been unexpectedly
      found in bone tissue of Irp2-/- mice. Irp2-/- mice exhibit reduced bone iron
      content and osteoporosis. Decreased circulating 25(OH)D3 levels promoted activity
      of osteoclast, while impaired activity of osteoblast may contribute to
      pathogenesis of osteoporosis. And, reduced bone iron content may not be totally
      caused by TfR1-dependent pathways.

PMID- 30191283
TI  - Atrophic Gastritis as a Risk Factor for Bone Loss in Premenopausal Women in Their
      40s: A Retrospective Cohort Study.
AB  - This study assessed the effects of atrophic gastritis on bone mineral density
      (BMD) in premenopausal women in their 40s. We performed a retrospective analysis
      of medical records of premenopausal women in their 40s who underwent a health
      checkup, esophagogastroduodenoscopy, and bone densitometry at least thrice, 24
      months apart, between January 2006 and December 2016. Based on first-visit
      esophagogastroduodenoscopy results, patients were divided into atrophic and non
      atrophic gastritis groups; BMD changes over time were analyzed. Patients were
      further divided into subgroups depending on atrophic gastritis persistence;
      differences and absolute changes in BMD were assessed. BMD in both groups
      exhibited group-by-time interaction (p < 0.001). After adjusting for confounding
      factors, the mean BMD was significantly different at the 24-month and the 48
      month follow-up (p = 0.049, p < 0.001, respectively). Subgroup analysis after
      adjusting for confounding factors showed a mean BMD of 1.128 and 1.104 at
      baseline, 1.110 and 1.100 at the 24-month follow-up, and 1.106 and 1.065 at the
      48-month follow-up for persistent atrophic and non-atrophic gastritis groups,
      respectively. The difference between mean BMD was not significant at baseline (p
      = 0.171), but was significant at the 24-month and 48-month follow-ups (p = 0.044
      and p < 0.001, respectively). Absolute changes in BMD over 48 months were - 0.010
      and - 0.051 for the two subgroups, which was significantly different (p < 0.001).
      Atrophic gastritis reduces BMD in premenopausal women in their 40s. Patients with
      atrophic gastritis exhibited lower BMD than patients without, and patients with
      persistent atrophic gastritis exhibited a greater decrease in BMD.

PMID- 30191284
TI  - Heart-sparing volumetric modulated arc therapy for whole lung irradiation.
AB  - PURPOSE: Whole lung irradiation (WLI) is indicated for subgroups of patients with
      lung metastases from Wilms' tumor (nephroblastoma). WLI has traditionally been
      performed with an anterior/posterior field arrangement with poor potential for
      heart sparing; thus, new techniques are desirable to achieve a lower dose to the
      heart. MATERIALS AND METHODS: We utilized volumetric modulated arc therapy (VMAT)
      for WLI with 18 Gy in a patient with metastatic nephroblastoma. The planning
      results were compared against a three-dimensional (3D) conformal plan. RESULTS:
      VMAT resulted in adequate target volume coverage with the prescribed dose. Mean
      heart dose was 10.2 Gy. The dose to organs at risk (OAR) was generally more
      favorable with VMAT when compared with a 3D-conformal radiotherapy plan.
      DISCUSSION: WLI with VMAT provides superior sparing of OARs and especially a
      considerably lower dose to the heart.

PMID- 30191285
TI  - Comparison of relative and absolute rectal dose-volume parameters and clinical
      correlation with acute and late radiation proctitis in prostate cancer patients.
AB  - PURPOSE: To compare relative and absolute dose-volume parameters (DV) of the
      rectum and their clinical correlation with acute and late radiation proctitis
      (RP) after radiotherapy (RT) for prostate cancer (PCa). PATIENTS AND METHODS: 366
      patients received RT for PCa. In total, 49.2% received definitive RT, 20.2%
      received postoperative RT and 30.6% received salvage RT for biochemical
      recurrence. In 77.9% of patients, RT was delivered to the prostate or prostate
      bed, and additional whole pelvic RT was performed in 22.1%. 33.9% received 3D-RT,
      and 66.1% received IMRT. The median follow-up was 59.5 months (18.0-84.0 months).
      The relative (in %) and absolute (in ccm) rectal doses from 20-75 Gy including
      the receiver operating characteristics curves (rAUC) from 30-65 Gy (in % and ccm)
      and several other clinical parameters were analyzed in univariate and
      multivariate analyses. We performed the statistical analyses separately for the
      entire cohort (n = 366), patients with (n = 81) and without (n = 285) pelvic RT,
      comparing RP vs. RP >= grade I. RESULTS: With the exception of the V50Gyccm (p =
      0.02) in the univariate analyses for acute RP in the entire patient cohort, no
      absolute DV parameter (in ccm) was statistically significant associated with
      either acute or late RP. In the multivariate analyses, 3D-RT (p < 0.008) and
      rAUCV30-50 Gy% (p = 0.006) were significant parameters for acute RP for the
      entire cohort, and the V50Gy% (p = 0.01) was the significant parameter for
      patients with pelvic RT. The rAUCV40-50 Gy% (p = 0.004) was significant for RT to
      the prostate/prostate bed. Regarding the statistical analysis for late RP, the
      rAUCV30-65 Gy% (p = 0.001) was significant for the entire cohort, and rAUCV30-50
      Gy% (p = 0.001) was significant for RT of the prostate/prostate bed. No parameter
      was significant in patients with pelvic RT. CONCLUSION: Absolute DV parameters in
      ccm are not required for RT in PCa patients.

PMID- 30191286
TI  - Characterization of the tissue crossing the supratrochlear aperture of the
      humerus using histochemical techniques.
AB  - INTRODUCTION: The supratrochlear aperture (STA) is the opening observed in the
      septum that separates the olecranon from the coronoid fossae. Numerous studies
      have shown that there is considerable variation in the occurrence of this feature
      within and among populations. MATERIALS AND METHODS: Cadavers (n = 43) were
      assessed for the presence of the STA by means of X-ray. Ten samples of STA
      bearing bones and an equal number of controls without STA were obtained from
      cadavers using a hole saw. These samples were decalcified, fixed in formalin and
      processed for histological assessment in differing (ascending) grades of alcohol
      before being embedded in paraffin wax. Sections (10 um thick) were stained with
      haematoxylin and eosin (H&E) for general architecture as well as the rapid one
      step Mallory-Heidenhain stain for bone and connective tissue. RESULTS: The STA
      samples exhibited an abundance of connective tissue arranged in regular bundles
      of fibers across the STA. In contrast, the controls showed only bone tissue in
      the septum. DISCUSSION AND CONCLUSION: The arrangement of connective tissue
      fibers organized in regular bundles is a characteristic of strength, which may
      indicate that the STA is under sustained stress or pressure from the olecranon
      and coronoid processes of the ulna. It remains debatable whether the STA should
      continue to be considered as a foramen in life as we demonstrate that it is
      obliterated by connective tissue. It contains no neurovascular structures, making
      it unlike other structures defined as foramina.

PMID- 30191287
TI  - Investigation on the measurement sites of the cross-sectional areas of the
      gluteus maximus and gluteus medius.
AB  - PURPOSES: To verify the relationship between muscle volume and muscular strength
      of different cross-sectional areas (CSAs) of the gluteus maximus and medius, and
      to clarify the effective evaluation index. METHODS: Twenty healthy adults were
      enrolled in this cross-sectional study. Magnetic resonance images were evaluated,
      and CSAs of the gluteus maximus and medius were calculated. Calculation sites
      were the peak CSA, lowest end of the sacroiliac joint CSA, and just above the
      femoral head CSA. Muscle volume and muscular strength were measured. The
      correlation between muscular CSA, muscle volume, and muscular strength was
      verified using Pearson's correlation coefficient (p < 0.05). One-way analysis of
      variance and the Tukey-Kramer test were used to verify differences in each CSA (p
      < 0.05). RESULTS: A significantly positive correlation was found between muscular
      CSA, muscle volume, and muscular strength of both muscles (p < 0.05). For the
      gluteus maximus, the muscular CSA calculated just above the femoral head showed a
      significantly larger value than that calculated at the lowest end of the
      sacroiliac joint (p < 0.05). For the gluteus medius, the peak CSA and muscular
      CSA calculated at the lowest end of the sacroiliac joint were significantly
      larger than that calculated just above the femoral head (p < 0.05). CONCLUSIONS:
      The maximum CSA of the gluteus maximus was found just above the femoral head and
      that of the gluteus medius was near the lowest end of the sacroiliac joint;
      hence, CSAs should be calculated at these sites. The CSA reflected muscle volume
      and strength.

PMID- 30191288
TI  - Engineering recombinant Lactococcus lactis as a delivery vehicle for BPC-157
      peptide with antioxidant activities.
AB  - Lactic acid bacteria (LAB) are attractive hosts for the expression of
      heterologous proteins and can be engineered to deliver therapeutic proteins or
      peptides to mucosal surfaces. The gastric stable pentadecapeptide BPC-157 is able
      to prevent and treat gastrointestinal inflammation by reducing the production of
      reactive oxygen species (ROS). In this study, we used LAB Lactococcus lactis as a
      vector to deliver BPC-157 by surface display and trypsin shedding or by secretion
      to the growth medium. Surface display of BPC-157 was achieved by fusing it with
      basic membrane protein A (BmpA) or with the peptidoglycan binding domain of AcmA
      and Usp45 secretion signal. While the expression of BmpA-fusion proteins was
      higher than that of AcmA/Usp45-fusion protein, the surface display ability of BPC
      157 was approximately 14-fold higher with AcmA/Usp45-fusion protein. Release of
      BPC-157 from the bacterial surface or from isolated fusion proteins by
      trypsinization was demonstrated with anti-BPC-157 antibodies or by mass
      spectrometry. The concentration of BPC-157 delivered by surface display via
      AcmA/Usp45-fusion was 30 ng/ml. This increased to 117 ng/ml by Usp45 signal
      mediated secretion, making the latter the most effective lactococcal delivery
      approach for BPC-157. Secreted BPC-157 significantly decreased ROS production in
      149BR fibroblast cell model, suggesting its potential benefit in the treatment of
      intestinal inflammations. Additionally, a comparison of different modes of small
      peptide delivery by L. lactis, performed in the present study, will facilitate
      the future use of L. lactis as peptide delivery vehicle.

PMID- 30191289
TI  - Effects of hydraulic retention time on the performance of algal-bacterial-based
      aquaponics (AA): focusing on nitrogen and oxygen distribution.
AB  - The effects of hydraulic retention time (HRT) on the performance of algal
      bacterial-based aquaponics (AA) were investigated in this study. Both the highest
      fish growth and algal biomass increase were observed in the AA system at 2-day
      HRT, resulting in the highest nitrogen utilization efficiency (NUE) (39.28%) in
      this microcosm. On the contrary, ammonia oxidation bacteria (AOB) abundance at 4
      day HRT was approximately ten times higher than that at 2-day HRT, since longer
      HRT would benefit bacterial growth. The 15N labeling study showed that microalgae
      assimilation was the main pathway of NH4+ removal in the AA system, and oxygen
      produced by microalgae could in situ support complete nitrification, thus leading
      to much lower NH4+ concentrations at 2-day HRT. Accordingly, better water quality
      was achieved at 2-day HRT. Considering all the factors, HRT of 2-day was
      considered to be optimal for the AA system.

PMID- 30191290
TI  - The pSG5-based thermosensitive vector family for genome editing and gene
      expression in actinomycetes.
AB  - Actinomycetes are the most important producers of secondary metabolites for
      medical, agricultural and industrial applications. Efficient engineering of
      bacterial genomes to improve their biosynthetic capabilities largely depends on
      the available arsenal of tools and vectors. One of the most widely used vector
      systems for actinomycetes is derived from the Streptomyces ghanaensis DSM2932
      plasmid pSG5. pSG5 is a broad host range multicopy plasmid replicating via a
      rolling circle mechanism. The unique feature of pSG5, which distinguishes it from
      other Streptomyces plasmids, is its naturally thermosensitive mode of
      replication. This allows the efficient elimination of the plasmid from its host
      by simply shifting the incubation temperature to non-permissive 37-39  degrees C.
      This property makes pSG5 derivatives ideal facultative suicide vectors required
      for selection of gene disruption/gene replacement, transposon delivery or
      CRISPR/Cas9-mediated genome editing. Whereas these techniques depend on the fast
      elimination of the vector, stably replicating expression vectors for the
      production of recombinant proteins have been constructed more recently. This mini
      review describes the generation and application of the pSG5 vector family,
      highlighting the specific features of the distinct vector plasmids.

PMID- 30191292
TI  - Management of liver hydatid cyst with cystobiliary communication and acute
      cholangitis: a 27-year experience.
AB  - PURPOSE: The rupture of the hydatid cyst into the bile ducts is a common and
      serious complication. The rupture can be latent or revealed after a complication
      such as acute cholangitis. The objective of this study was to discuss the
      clinical features, radiographic findings, and surgical treatment of this rare
      complication. METHODS: A retrospective analysis of patients operated for acute
      cholangitis caused by hydatid cyst between January 1990 and May 2016 was
      conducted. RESULTS: Our study included 55 cases of acute cholangitis caused by
      ruptured hydatid cyst: 35 were men and 20 were women. Five patients had medical
      history of hydatid cyst. On imaging, all patients had a dilated bile duct. In 51
      cases, there was a single hydatid cyst. Hydatid cysts with fistula were located
      in the right lobe of the liver in 49 cases and in the left lobe in 6 cases. Seven
      patients underwent an emergency surgery after admission, while others were
      operated after 3-8 days. A conservative procedure associated with drainage was
      applied in 49 cases. Endoscopic treatment was performed in four cases which
      failed in two cases. Twenty-eight cases developed postoperative complications,
      among which the most common complication was biliary fistula (n - 17). There were
      eight cases of postoperative deaths (14.5%). CONCLUSIONS: Liver hydatid cyst with
      cystobiliary communication and superadded acute cholangitis is a serious clinical
      problem requiring the early diagnosis and surgery in the absence of endoscopic
      therapy.

PMID- 30191291
TI  - A hydroquinone-specific screening system for directed P450 evolution.
AB  - The direct hydroxylation of benzene to hydroquinone (HQ) under mild reaction
      conditions is a challenging task for chemical catalysts. Cytochrome P450 (CYP)
      monooxygenases are known to catalyze the oxidation of a variety of aromatic
      compounds with atmospheric dioxygen. Protein engineering campaigns led to the
      identification of novel P450 variants, which yielded improvements in respect to
      activity, specificity, and stability. An effective screening strategy is crucial
      for the identification of improved enzymes with desired characteristics in large
      mutant libraries. Here, we report a first screening system designed for screening
      of P450 variants capable to produce hydroquinones. The hydroquinone
      quantification assay is based on the interaction of 4-nitrophenylacetonitrile
      (NpCN) with hydroquinones under alkaline conditions. In the 96-well plate format,
      a low detection limit (5 MUM) and a broad linear detection range (5 to 250 MUM)
      were obtained. The NpCN assay can be used for the quantification of
      dihydroxylated aromatic compounds such as hydroquinones, catechols, and
      benzoquinones. We chose the hydroxylation of pseudocumene by P450 BM3 as a target
      reaction and screened for improved trimethylhydroquinone (TMHQ) formation. The
      new P450 BM3 variant AW2 (R47Q, Y51F, I401M, A330P) was identified by screening a
      saturation mutagenesis library of amino acid position A330 with the NpCN assay.
      In summary, a 70-fold improved TMHQ formation was achieved with P450 BM3 AW2 when
      compared to the wild type (WT) and a 1.8-fold improved TMHQ formation compared to
      the recently reported P450 BM3 M3 (R47S, Y51W, A330F, I401M).

PMID- 30191293
TI  - Unusual purpura fulminans after heart transplantation.

PMID- 30191295
TI  - What's new on emerging resistant Candida species.

PMID- 30191294
TI  - White paper: statement on conflicts of interest.
AB  - INTRODUCTION: Conflicts of interest are a normal part of human social
      intercourse. They become problematic when there is a power differential between
      participants in the setting of relationships requiring a high degree of trust, as
      in healthcare. In this white paper we consider how these conflicts may be
      detected and mitigated. METHODS: Following Medline search and reference chaining,
      we undertook a narrative review of the literature with iterative discussion.
      RESULTS: Conflicts of interest may be financial, professional or personal, and
      may operate at the level of the individual or the organisation. Unmanaged, they
      become a source of bias which places the interests of the professional or the
      organisation before those of the patient. Reported with increasing frequency,
      conflicts damage trust, harm patients, and defraud the health system. We make 15
      recommendations for minimising conflicts of interest. CONCLUSIONS: Nationally
      funded open-access registries should be established to permit complete disclosure
      of financial, professional, and personal relationships with the potential for
      driving bias in research, clinical practice, or health management. Governance of
      disclosure should be the responsibility of employing organisations through annual
      staff appraisals, audited by national research integrity committees. Research
      fraud should incur suspension of the license to practice. Organisations should
      monitor staff perceptions of ethical climate to enhance awareness of staff
      behaviours and the potential for misconduct driven by academic pressures. Clear
      separation of advisory and voting roles is needed in best practice guideline
      panels. Professional societies and scientific journals should display conflict of
      interest policies for their own staff and officers as well as for speakers and
      authors. Undergraduates should not be exposed to pharmaceutical promotions
      masquerading as education. Undergraduate and postgraduate training programmes
      should include teaching about managing conflicts of interest and identifying
      research misconduct.

PMID- 30191296
TI  - Invasive hemodynamics and cardiac biomarkers to predict outcomes after
      percutaneous edge-to-edge mitral valve repair in patients with severe heart
      failure.
AB  - BACKGROUND: Percutaneous mitral valve repair (PMVR) via MitraClip implantation is
      a therapeutic option for high-risk or non-surgical candidates with severe mitral
      regurgitation (MR) and advanced stages of heart failure (HF). However, these
      patients have a high mortality despite PMVR, and predictors for outcomes are not
      well established. Here, we evaluated invasive hemodynamics, echocardiography
      parameters, and biomarkers to predict outcomes after PMVR in severe HF patients.
      METHODS: Patients with reduced ejection fraction (EF) and severe and moderate-to
      severe MR undergoing PMVR at our centre between September 2009 and January 2016
      were analysed retrospectively. Inclusion criteria were: left ventricular EF <
      45%, preoperative right heart catheterization, successful MitraClip deployment
      ("technical success"), and follow-up for at least 1 year after the procedure.
      Data from preoperative right heart catheterization, echocardiography, and
      biomarkers were assessed. Primary endpoint was all-cause mortality at 1 year
      after PMVR. We performed univariate and multivariate Cox regression analyses and
      generated a risk score to predict outcomes. RESULTS: Of 174 patients with PMVR
      and severe HF, 79.9% had functional MR. Mean EF was 25% (17.2; 30.7) and advanced
      New York Heart Association functional class was prevalent (class II: 13%; class
      III: 70%; and class IV: 17%). The cumulative incidences of all-cause death were
      6.9% and 17.8% at 30 days and 1 year, respectively. In the Cox multivariate
      model, high-sensitive troponin T [hsTnT; hazard ratio (HR) 1.01; confidence
      interval (CI) 1.01-1.02; p < 0.0001] and mixed venous O2-saturation (HR 0.92; CI
      0.89-0.96; p < 0.0001) were found to significantly and independently predict
      outcomes. A simple risk score including these two parameters was sufficient to
      discriminate between low- and high-risk patients (HR 7.22; CI 3.4-15.5; p <
      0.001). CONCLUSION: In a cohort of patients with severe HF undergoing PMVR,
      patients with elevated hsTnT and reduced mixed venous O2-saturation carried the
      worst prognosis. A simple risk score including these two parameters may improve
      patient selection and outcomes after PMVR.

PMID- 30191297
TI  - Transfer of cyanobacterial carbon to a higher trophic-level fish community in a
      eutrophic lake food web: fatty acid and stable isotope analyses.
AB  - The dietary utilization of cyanobacterial carbon by fish communities is poorly
      understood. We examined the transfer of cyanobacterial carbon to fish in a
      eutrophic lake using fatty acid biomarkers and measuring the stable carbon
      isotope ratios of fatty acid and bulk nitrogen. We collected five species of fish
      (Hypomesus nipponensis, Carassius sp., Cyprinus carpio, Tridentiger brevispinis,
      and Gymnogobius castaneus) as well as the seston from June to November 2016 from
      Lake Hachiro, Japan. Cyanobacterial blooms were observed from August to October.
      From June to August, cyanobacterial fatty acid biomarkers (18:2omega6 and
      18:3omega3) accounted for only 1.4-4.3% of total fatty acids in these fish
      species, indicating a low contribution of cyanobacteria to fish diets during this
      period. However, the contribution of the cyanobacterial fatty acid biomarkers in
      these fish species increased sharply in September (10.5-17.1%), except in second
      year H. nipponensis. In September, the stable carbon isotope ratios of 18:3omega3
      in these fish species were almost equivalent to those in the seston, which was
      primarily composed of cyanobacteria. The trophic positions of the collected fish
      species ranged from 1.6 to 3.4, based on their stable nitrogen isotope values,
      indicating that some fish ingested cyanobacteria directly, while others acquired
      cyanobacteria indirectly, through the food chain. These findings indicate that
      cyanobacterial carbon is transferred up the food chain in eutrophic lake
      ecosystems with cyanobacterial blooms.

PMID- 30191298
TI  - The subfamily II catalytic subunits of protein phosphatase 2A (PP2A) are involved
      in cortical microtubule organization.
AB  - MAIN CONCLUSION: The subfamily II catalytic subunits of protein phosphatase 2A
      (PP2A) regulate the cortical microtubule dynamics in Arabidopsis, through
      interaction with TONNEAU2 (TON2)/FASS and modulation of alpha-tubulin
      dephosphorylation. Protein phosphatase 2A is a major protein phosphatase in
      eukaryotes that dephosphorylates many different substrates to regulate their
      function. PP2A is assembled into a heterotrimeric complex of scaffolding A
      subunit, regulatory B subunit, and catalytic C subunit. Plant PP2A catalytic C
      subunit (PP2AC) isoforms are classified into two subfamilies. In this study, we
      investigated the cellular functions of the Arabidopsis PP2AC subfamily II genes
      PP2AC-3 and PP2AC-4, particularly regarding the cortical microtubule (MT)
      organization. PP2AC-3 and PP2AC-4 strongly interacted with the B'' regulatory
      subunit TON2. Simultaneous silencing of PP2AC-3 and PP2AC-4 by virus-induced gene
      silencing (PP2AC-3,4 VIGS) significantly altered plant morphology in Arabidopsis,
      increasing cell numbers in leaves and stems. The leaf epidermis of PP2AC-3,4 VIGS
      plants largely lost its jigsaw-puzzle shape and exhibited reduced trichome branch
      numbers. VIGS of PP2AC-3,4 in Arabidopsis transgenic plants that expressed GFP
      fused beta-tubulin 6 isoform (GFP-TUB6) for the visualization of MTs caused a
      reduction in the cortical MT array density in the pavement cells. VIGS of TON2
      also led to similar cellular phenotypes and cortical MT patterns compared with
      those after VIGS of PP2AC-3,4, suggesting that PP2AC-3,4 and their interaction
      partner TON2 play a role in cortical MT organization in leaf epidermal cells.
      Furthermore, silencing of PP2AC-3,4 did not affect salt-induced phosphorylation
      of alpha-tubulin but delayed its dephosphorylation after salt removal. The
      reappearance of cortical MT arrays after salt removal was impaired in PP2AC-3,4
      VIGS plants. These results suggest an involvement of PP2AC subfamily II in the
      regulation of cortical MT dynamics under normal and salt-stress conditions in
      Arabidopsis.

PMID- 30191300
TI  - Response to: Choroidal thickness changes stratified by outcome in real-world
      treatment of diabetic macular edema.

PMID- 30191299
TI  - Retinal flow density by optical coherence tomography angiography is useful for
      detection of nonperfused areas in diabetic retinopathy.
AB  - PURPOSE: Fluorescein angiography (FA) has been conventionally used for detection
      of retinal nonperfused area (NPA) in diabetic retinopathy (DR) in spite of its
      qualitative evaluation. Optical coherence tomography angiography (OCTA) has been
      recently reported to be useful for the quantification of retinal vascular
      disorder in DR. In this study, we examined whether retinal flow density (FD)
      measurement in OCTA was useful for NPA detection in DR. METHODS: The study
      included 41 eyes from 29 patients with DR who underwent FA and OCTA. Regions
      surrounded by arteries or veins were extracted in the OCTA image, and the FDs in
      each region were measured by Image J. Furthermore, each region was classified as
      NPA or perfused area (PA) in FA. The receiver operating characteristic (ROC)
      curve was prepared by logistic regression analysis of the FD. The AUC (area under
      the ROC curve) and cutoff value of FD were also calculated. RESULTS: Two hundred
      fifty-two regions were analyzed and classified into 38 NPA regions and 214 PA
      regions using FA. FD of each capillary plexus in NPA was significantly smaller
      than in PA (p < 0.0001). The AUC of total capillary plexus layers (TCP),
      superficial capillary plexus layer (SCP), and deep capillary plexus layer (DCP)
      was 0.975, 0.974, and 0.971, respectively. All areas, where the FD was more than
      the cutoff value (0.07 in TCP), were diagnosed with PA. Three areas with
      intraretinal microvascular abnormalities (IRMA) were diagnosed as PA despite
      being below the cutoff value. CONCLUSIONS: FD measurement in OCTA is useful for
      NPA detection in DR.

PMID- 30191301
TI  - Outcomes of benign intraductal papillomas diagnosed on core biopsy: a review of
      104 cases with subsequent excision from a single institution.
AB  - A diagnosis of papilloma with atypia on core biopsy (CB) requires excision, as
      the risk of associated malignancy is high (average 36.9%). The management of
      benign intraductal papillomas (IP) diagnosed on CB is controversial due to
      varying upgradation rates (0-29%, average 7%) reported on excision. Our aim was
      to study the clinical, radiological, and pathological features associated with
      benign IP upgradation at our institution. An electronic data base search (keyword
      papilloma), from Jan. 2000-Aug. 2015 identified 258 CBs. After exclusions, 104
      CBs of benign IPs with subsequent excisions from 101 females were reviewed. The
      clinical, radiological, and pathological features between IPs that had upgrades
      (defined as malignancy or atypical ductal hyperplasia) and non-upgraded IPs were
      compared using descriptive statistics. Studies of benign IP on CB with at least
      50 follow-up excisions published between 2008 and 2016 were analyzed. Residual IP
      was present in 83.6% (87/104) of reviewed excisions. There were six upgrades
      (5.6%) (4 to malignancy (3.8%) and 2 to atypical ductal hyperplasia).Upgrades
      were associated with mass on imaging with a trend to significance (p = .05). Two
      cases with malignant upgrade had a history of contralateral cancer. An analysis
      of 25 published studies showed an average malignant upgrade of 5.7% (182/3164).
      The majority of benign IP are not upgraded on excision; thus, not all need to be
      excised. Those that may warrant excision are those with prior history of
      carcinoma, those with a mass on imaging, and/or suboptimal or imaging-discordant
      CB sampling.

PMID- 30191302
TI  - Elective replacement of intravenous cannula in neonates-a randomised trial.
AB  - Peripheral intravenous cannula (PIVC) insertion is one of the most common
      invasive procedures performed in neonates and is frequently associated with
      adverse events. There are no studies in the neonatal population looking at the
      possibility of reducing the risk of PIVC-related complications by elective
      replacement of PIVC. A randomised, non-blinded, control trial was conducted in a
      tertiary level neonatal unit in Melbourne, Australia, to examine rates of
      extravasation in neonates with elective replacement of PIVC as compared to
      standard practice. Neonates born at 32 weeks of gestation or more were randomly
      assigned to have their PIVC replaced electively (every 72-96 h) or when
      clinically indicated in a 1:1 allocation ratio after parental consent. Primary
      outcome studied was rate of extravasation. Secondary outcomes included rates of
      phlebitis, leakage or spontaneous dislodgement of PIVC. One hundred thirteen
      infants were enrolled. Extravasation was noted in 33 (60%) of standard practice
      group vs. 28 (48.3%) of elective replacement (RR 0.80, CI 0.57-1.13, p = 0.21)
      infants. Time to first extravasation was similar between the groups (hazard ratio
      0.69, CI 0.42-1.15). Extravasation events per 1000 IV hours were also similar
      between groups. Similar results were seen by both intention to treat and per
      protocol analyses. There was an increase in leaking rates (HR1.98, CI 1.03-3.81,
      p = 0.04) in the elective group, while phlebitis and spontaneous dislodgement
      rates were similar to standard group.Conclusion: Elective replacement of PIVC in
      neonates is not associated with reduction in extravasation rates.Trial
      registration: This trial has been registered with the Australian and New Zealand
      Clinical Trials Register. Identifier: ACTRN12615000827538. What is Known: * The
      reported incidence of extravasation injury is as high as 70% in the neonatal and
      paediatric population and has an association with cannula dwell time. * Adult
      studies have done to look at the possibility of reducing intravenous cannula
      related complications with routine replacement of the cannulas but no similar
      studies have been done in the neonatal population. What is New: * Routine
      replacement of intravenous cannula in neonates between 72 and 96 h of use does
      not reduce the rate of extravasation injuries. * There might be some added
      complications associated with such a practice.

PMID- 30191304
TI  - 3D fluid attenuated inversion recovery (FLAIR) magnetic resonance imaging at
      different stages of otosclerosis.
AB  - PURPOSE: The aim of this work is to study otosclerotic patients by 3D-FLAIR
      (fluid attenuated inversion recovery) sequence magnetic resonance imaging (MRI)
      with and without Gadolinium administration (-/+ Gd), to understand whether there
      is a direct relationship between radiological findings at 3D FLAIR MRI sequences
      and some clinical features of otosclerosis, such as the presence and entity of
      sensorineural involvement, duration of disease, patient gender, and other
      factors. METHODS: 38 patients affected by different stages of unilateral or
      bilateral otosclerosis underwent 3D FLAIR MRI+/- Gd. 11 subjects with normal
      hearing, previously submitted to 3T MRI for other minor diseases, unrelated with
      otosclerosis, had been retrospectively enrolled as control group. RESULTS: We
      found significant correlations between 3D FLAIR MRI findings and some clinical
      features of otosclerosis, such as severity of cochlear damage (in terms of entity
      of sensorineural loss) and duration of disease. These findings indicate that at
      3D-FLAIR MRI different patterns may depend on the level of blood labyrinth
      barrier damage in the cochlea, and be related to different stages of cochlear
      involvement in otosclerotic patients. CONCLUSIONS: We believe that our findings
      may contribute in understanding the pathogenesis of cochlear damage in
      otosclerosis and may have further prognostic value. Our results led us to
      consider the possible use of 3D-FLAIR sequences in monitoring the effectiveness
      of any medical therapy of otosclerosis and in selecting the patients eligible for
      treatment.

PMID- 30191303
TI  - Narrow band imaging endoscopy improves visualization of vessels of the perforated
      tympanic membrane.
AB  - PURPOSE: Because successful healing of a tympanic membrane perforation (TMP)
      depends upon the maintenance of blood supply to the injured area, we assessed the
      usefulness of narrow band imaging (NBI) video endoscopy to evaluate its
      vascularization. To our knowledge, the use of NBI to assess tympanic membrane
      (TM) vascular patterns has never been attempted. METHODS: Prospective
      observational study. NBI and cold white light (CWL) flexible videoendoscopy was
      used to explore perforated TMs of 100 patients. Main outcome measures were
      visualization of vessels among abnormal TM findings: monomeric areas (MA) (n =
      6), myringosclerosis plaques (MP) (n = 65) and perforation edges (n = 100). They
      were graded by a vascular otoendoscopic score (VOS) comparing both types of
      lights (Wilcoxon test). Location and vascularization patterns were analyzed
      (Fisher's test). RESULTS: NBI was better to observe vascularization of 32% of
      perforation edges and 75.4% of MP (p < 0.001). NBI displayed higher (better) VOS
      when evaluating TMP edges (1.05 vs. 0.73) and MP (1.56 vs. 0.81, p < 0.001). The
      majority of TMP edges showed a ring pattern (66%), followed by irregular (19%),
      avascular (12%) and radial patterns (3%). The avascular pattern was more frequent
      in posterior perforations (p = 0.003). The radial pattern was most frequently
      found in MP, especially at posterior quadrants (p = 0.048). MA presented an
      irregular pattern in 83.3% of TMs. CONCLUSIONS: NBI videoendoscopy is a promising
      non-invasive technique, superior to CWL for visualizing vessels among TMP edges
      and MP, based on further study, could become a supplementary diagnostic tool in
      the workup of TMP and the decision-making surgical field.

PMID- 30191305
TI  - Macular degeneration and occupational risk factors: a systematic review.
AB  - PURPOSE: Macular degeneration is a multi-factorial disease, leading cause of
      blindness for people over 50 years old in developed countries. To date, the
      knowledge on possible occupational factors involved in the development of the
      disease is scant. METHOD: We performed a systematic scientific literature search
      on the association between macular degeneration and occupational risk factors
      searching the MedLine and Scopus databases. RESULTS: We examined 158 articles
      and, according to the inclusion criteria, 13 peer-reviewed studies evaluating
      occupational risk factors for macular degeneration or reporting the frequency of
      the disease in specific groups of workers were included in the review. Ten on
      thirteen articles evaluated the presence of macular degeneration in workers
      exposed to solar radiation. Only one study found that non-specific history of
      occupational chemical exposure was associated with the disease. Two studies
      showed an association between macular degeneration and the general category of
      "blue-collar" workers, but they did not identify the specific risk factors
      involved. CONCLUSIONS: To date few studies have examined occupational risk
      factors for macular degeneration. Nevertheless, available data indicate that long
      term occupational solar radiation exposure, in particular for its blue-light
      component, is associated with macular degeneration in outdoor workers.

PMID- 30191306
TI  - Clinically significant radiographic parameter for thoracic myelopathy caused by
      ossification of the ligamentum flavum.
AB  - PURPOSE: To investigate radiographic parameters to improve the accuracy of
      radiologic diagnosis for ossification of ligamentum flavum (OLF)-induced thoracic
      myelopathy and thereby establish a useful diagnostic method for identifying the
      responsible segment. METHODS: We classified 101 patients who underwent surgical
      treatment for OLF-induced thoracic myelopathy as the myelopathy group and 102
      patients who had incidental OLF and were hospitalized with compression fracture
      as the non-myelopathy group between January 2009 and December 2016. We measured
      the thickness of OLF (TOLF), cross-sectional area of OLF (AOLF), anteroposterior
      canal diameter, and the ratio of each of these parameters. RESULTS: Most OLF
      cases with lateral-type axial morphology were in the non-myelopathy group and
      most with fused and tuberous type in the myelopathy group. Most grade-I and grade
      II cases were also in the non-myelopathy group, whereas grade-IV cases were
      mostly observed in the myelopathy group. The AOLF ratio was found to be the best
      radiologic parameter. The optimal cutoff point of the AOLF ratio was 33.00%, with
      87.1% sensitivity and 87.3% specificity. The AOLF ratio was significantly
      correlated with preoperative neurological status. CONCLUSIONS: An AOLF ratio
      greater than 33% is the most accurate diagnostic indicator of OLF-induced
      thoracic myelopathy. In cases of multiple-segment OLF, confirmation of cord
      signal change on MRI and an AOLF measurement will help determine the responsible
      segment. AOLF measurement will also improve the accuracy of diagnosis of OLF
      induced thoracic myelopathy in cases of grade III or extended-type axial
      morphology. These slides can be retrieved under Electronic Supplementary
      Material.

PMID- 30191307
TI  - Diverse roles of Tup1p and Cyc8p transcription regulators in the development of
      distinct types of yeast populations.
AB  - Yeasts create multicellular structures of varying complexity, such as more
      complex colonies and biofilms and less complex flocs, each of which develops via
      different mechanisms. Colony biofilms originate from one or more cells that,
      through growth and division, develop a complicated three-dimensional structure
      consisting of aerial parts, agar-embedded invasive parts and a central cavity,
      filled with extracellular matrix. In contrast, flocs arise relatively quickly by
      aggregation of planktonic cells growing in liquid cultures after they reach the
      appropriate growth phase and/or exhaust nutrients such as glucose. Creation of
      both types of structures is dependent on the presence of flocculins: Flo11p in
      the former case and Flo1p in the latter. We recently showed that formation of
      both types of structures by wild Saccharomyces cerevisiae strain BR-F is
      regulated via transcription regulators Tup1p and Cyc8p, but in a divergent
      manner. Biofilm formation is regulated by Cyc8p and Tup1p antagonistically: Cyc8p
      functions as a repressor of FLO11 gene expression and biofilm formation, whereas
      Tup1p counteracts the Cyc8p repressor function and positively regulates biofilm
      formation and Flo11p expression. In addition, Tup1p stabilizes Flo11p probably by
      repressing a gene coding for a cell wall or extracellular protease that is
      involved in Flo11p degradation. In contrast, formation of BR-F flocs is co
      repressed by the Cyc8p-Tup1p complex. These findings point to different
      mechanisms involved in yeast multicellularity.

PMID- 30191310
TI  - A systematic review and meta-analysis of metal versus plastic stents for drainage
      of pancreatic fluid collections: metal stents are advantageous.
AB  - BACKGROUND: The use of fully covered metal stents (FCSEMS) and specifically
      designed lumen apposing metal stents for transmural drainage of pancreatic fluid
      collections has become widespread. A systematic review published in 2015 did not
      support the routine use of metal stents for drainage of pancreatic fluid
      collections. However, recent studies have shown conflicting data; therefore a
      systematic review and meta-analysis was performed. METHOD: We conducted a
      database search for original comparative studies between plastic and metal
      stents. The random effects model was used to calculate pooled risk ratios (RR)
      with 95% confidence intervals (CI). Outcomes analysed were clinical success,
      adverse events and requirement of further intervention. RESULTS: The search
      identified 936 studies, 7 studies with 681 (340 metal, 341 plastic) patients met
      inclusion criteria and were included in the meta-analysis. Clinical success was
      achieved in 93.8% versus 86.2% in the metal and plastic groups, respectively, RR
      1.08 [95% CI 1.02-1.14]; p = 0.009. Adverse events were reduced for metal stents
      when compared with plastic (10.2% vs. 25.0%), RR 0.42 [95% CI 0.22-0.81]; p =
      0.010. Metal stent usage reduced bleeding (2.8% vs. 7.9%), RR 0.37; [95% CI 0.18
      0.75]; p = 0.006. Further intervention was required in 12.4% of patients in the
      metal stent group versus 26.7% for plastic stents, RR 0.54; [95% CI 0.22-1.29]; p
      = 0.165. CONCLUSIONS: The use of metal stents for drainage of pancreatic fluid
      collections is associated with improved clinical success, fewer adverse events
      and reduced bleeding compared to plastic stents.

PMID- 30191309
TI  - Identification of a perchloric acid-soluble protein (PSP)-like ribonuclease from
      Trichomonas vaginalis.
AB  - A perchloric acid-soluble protein (PSP), named here tv-psp1, was identified in
      Trichomonas vaginalis. It is expressed under normal culture conditions according
      to expressed sequence tag (EST) analysis. On the other hand, Tv-PSP1 protein was
      identified by mass spectrometry with a 40% of identity to human PSP (p14.1).
      Polyclonal antibodies against recombinant Tv-PSP1 (rTv-PSP1) recognized a single
      band at 13.5 kDa in total protein parasite extract by SDS-PAGE and a high
      molecular weight band analyzed by native PAGE. Structural analysis of Tv-PSP1,
      using dynamic light scattering, size exclusion chromatography, and circular
      dichroism spectroscopy, showed a trimeric structure stable at 7 M urea with 38%
      alpha-helix and 14% beta-sheet in solution and a molecular weight of 40.5 kD. Tv
      PSP1 models were used to perform dynamic simulations over 100 ns suggesting a
      stable homotrimeric structure. Tv-PSP1 was located in the nucleus, cytoplasm, and
      hydrogenosomes of T. vaginalis, and the in silico analysis by Search Tool for the
      Retrieval of Interacting Genes/Proteins (STRING) showed interactions with RNA
      binding proteins. The preliminary results of RNA degradation analysis with the
      recombinant Tv-PSP1 showed RNA partial deterioration suggesting a possible
      putative ribonuclease function.

PMID- 30191308
TI  - [Pain therapy for children and adolescents with hemophilia : Recommendations by
      an expert panel].
AB  - BACKGROUND: Children and adolescents with severe hemophilia commonly suffer from
      acute and chronic pain as a consequence of hemophilia-related bleeding.
      Intervention-related pain also plays a major role. Despite its high prevalence in
      this patient group, hemophilia-related pain is not always adequately addressed
      and sufficiently treated. OBJECTIVES: This paper discusses how to improve pain
      management for children and adolescents (0-18 years) with hemophilia and which
      specific features in this population should influence decisions in pain
      management. MATERIALS AND METHODS: An expert panel discussed challenges in pain
      treatment in children and adolescents with hemophilia. Recommendations are based
      on evidence and clinical experience. RESULT: Pain management in children with
      hemophilia needs improvement. Children with hemophilia are at risk of developing
      chronic pain and of suffering traumatization due to insufficient pain management.
      Pain therapy can be challenging in these children as both their age and the
      underlying disease limit the options in particular in pain medication. The expert
      panel developed recommendations to improve pain management in children with
      hemophilia.

PMID- 30191311
TI  - Comparative transcriptome analysis shows the defense response networks regulated
      by miR482b.
AB  - KEY MESSAGE: The transcriptomic profile in the leaves of miR482b-overexpressing
      tomato plants revealed that miR482b may suppress alpha-linolenic acid metabolism,
      cysteine and methionine metabolism, plant-pathogen interaction, and the MAPK
      pathway to reduce resistance to Phytophthora infestans. Our previous study showed
      that tomato miR482b acted as a negative regulator during tomato resistance to
      Phytophthora infestans by silencing NBS-LRR genes. To investigate pathways
      related to miR482b, the transcriptomic profile of tomato plants that
      overexpressed miR482b was constructed. A total of 47,124,670 raw sequence reads
      from the leaves of miR482b-overexpressing tomato plants were generated by
      Illumina sequencing. A total of 746 genes in miR482b-overexpressing tomato plants
      were found to show significantly differential expression relative to those in
      wild-type tomato plants, including 132 up-regulated genes and 614 down-regulated
      genes. GO and KEGG enrichment analyses showed that plant-pathogen interaction,
      the MAPK pathway, and the pathways related to JA and ET biosynthesis were
      affected by miR482b in tomato. qRT-PCR results showed that all the enriched genes
      in these pathways were down-regulated in tomato plants that overexpressed miR482b
      and up-regulated in tomato plants that overexpressed an NBS-LRR gene
      (Soly02g036270.2, the target gene of miR482b). After P. infestans infection, the
      expression of the enriched genes showed a time-dependent response, and the genes
      played different roles between resistant tomato (Solanum pimpinellifolium L3708)
      and tomato susceptible to P. infestans (S. lycopersicum Zaofen No. 2). Our
      results have, therefore, demonstrated that miR482b is an important component of
      defense response network. This will also help to identify candidate genes
      involved in plant-pathogen interaction.

PMID- 30191312
TI  - Correction to: Differences in gut microbiota associated with age, sex, and stool
      consistency in healthy Japanese subjects.
AB  - The authors would like to correct the errors in the publication of the original
      article. The correction details are given below for your reading.

PMID- 30191313
TI  - Recommendations by the DOG for the planning of clinical trials on behalf of third
      parties : March 2018.

PMID- 30191314
TI  - Multiplex analysis of genetic polymorphisms within UGT1A9, a gene involved in
      phase II of Delta9-THC metabolism.
AB  - We present a novel multiplex assay for the simultaneous detection of 12
      polymorphisms within the UGT1A9 sequence, which codes for enzymes involved in
      phase II biotransformation. The assay combines a multiplexed amplification step
      with single-base extension sequencing. The method described here is fast, cost
      effective, and easy-to-use, combining the relevant features of screening methods
      for research and diagnostics in pharmacogenetics. To validate the assay, we
      tested reproducibility and sensitivity and analysed allele frequencies of 110
      Caucasian individuals. Furthermore, we describe combining genetic information of
      individuals consuming Cannabis sativa products with respective plasma
      concentrations of a metabolite.

PMID- 30191315
TI  - The influence of threat on perceived spatial distance to out-group members.
AB  - A classic example of discriminatory behavior is keeping spatial distance from an
      out-group member. To explain this social behavior, the literature offers two
      alternative theoretical options that we label as the "threat hypothesis" and the
      "shared-experience hypothesis". The former relies on studies showing that out
      group members create a sense of alertness. Consequently, potentially threatening
      out-group members are represented as spatially close allowing the prevention of
      costly errors. The latter hypothesis suggests that the observation of out-group
      members reduces the sharing of somatosensory experiences and, thus, increases the
      perceived physical distance between oneself and others. In the present paper, we
      pitted the two hypotheses against each other. In Experiment 1, Caucasian
      participants expressed multiple implicit "Near/Far" spatial categorization
      judgments from a Black-African Avatar and a White-Caucasian Avatar located in a
      3D environment. Results indicate that the Black-African Avatar was categorized as
      closer to oneself, as compared with the White-Caucasian Avatar, providing support
      for "the threat hypothesis". In Experiment 2, we tested to which degree perceived
      threat contributes to this categorization bias by manipulating the avatar's
      perceived threat orthogonally to group membership. The results indicate that
      irrespective of group membership, threatening avatars were categorized as being
      closer to oneself as compared with no threatening avatars. This suggests that
      provided information about a person and not the mere group membership influences
      perceived distance to the person.

PMID- 30191316
TI  - Visuo-motor interference with a virtual partner is equally present in cooperative
      and competitive interactions.
AB  - Automatic imitation of observed actions is thought to be a powerful mechanism,
      one that may mediate the reward value of interpersonal interactions, but that
      could also generate visuo-motor interference when interactions involve
      complementary movements. Since interpersonal coordination seems to be crucial
      both when cooperating and competing with others, the questions arises as to
      whether imitation-and thus visuo-motor interference-occurs in both scenarios. To
      address this issue, we asked human participants to engage in high- or low
      interactive (Interactive or Cued condition, respectively), cooperative or
      competitive, joint reach-to-grasps with a virtual partner. More specifically,
      interactions occurred in: (i) a Cued condition, where participants simply adapted
      their movement timing to synchronize with (during cooperation) or anticipate
      (during competition) the virtual partner's grasp; (ii) an Interactive condition
      requiring the same adaptation, as well as a real-time selection of their action
      according to the virtual character's movement. To simulate a realistic human
      human interaction, the virtual character would change its movement speed in
      consecutive trials according to participants' behaviour. Results demonstrate that
      visuo-motor interference-as indexed by movement kinematics (higher maximum wrist
      height during complementary compared to imitative power grips)-emerge in both
      cooperative and competitive motor interactions only when predictions about the
      partner's movements are needed to perform one's own action (interactive
      condition). These results support the idea that simulative imitation is heavily
      present when individuals need to match their behaviours closely.

PMID- 30191317
TI  - Plaque erosion versus rupture characterization by optical frequency domain
      imaging before and after coronary stenting following successful fibrinolysis for
      ST-segment elevation myocardial infarction.
AB  - Intracoronary thrombus burden affects the quality of myocardial reperfusion in
      the setting of ST-elevation myocardial infarction (STEMI). We aimed to study the
      characteristics of the plaque and thrombus assessed by intracoronary optical
      frequency domain imaging (OFDI) according to the presence of plaque rupture or
      erosion in STEMI patients treated with successful fibrinolysis. Pre-stenting
      thrombus and post-stenting atherothrombotic burden were compared between plaque
      rupture and erosion. Twenty-seven consecutive patients were included: 17 (63%)
      had OFDI-plaque rupture and 10 (37%) had OFDI-erosion. Thrombus volume and burden
      were significantly higher in case of rupture compared to erosion at baseline
      (13.4 +/- 18.4 vs 2.8 +/- 2.3 mm3; p = 0.03 and 33.8 +/- 17.5 vs 17.5 +/- 9.9%; p
      = 0.007, respectively). In the rupture group, the core of the thrombus consisted
      dominantly of red thrombus evenly distributed along the entire culprit plaque. In
      the erosion group, it consisted dominantly of white thrombus with a focal
      distribution near the minimal lumen area zone. After stenting, the
      atherothrombotic volume, burden and its distribution, as well as angiographic
      estimators of myocardial reperfusion were similar between groups. Our study
      showed that pre-PCI thrombus amount, typesetting and distribution are mainly
      linked to the underlying mechanism of STEMI. After stenting, the atherothrombotic
      burden and its distribution were similar between the groups.

PMID- 30191318
TI  - Aortic remodeling with frozen elephant trunk technique for Stanford type A aortic
      dissection using Japanese J-graft open stent graft.
AB  - The frozen elephant trunk (FET) technique allows single-stage extended surgical
      repair of Stanford type A aortic dissection and has shown promotion of aortic
      remodeling by maintaining the true lumen flow and facilitating its expansion and
      by promoting false lumen thrombosis. However, few studies have compared the
      effectiveness of FET technique, in terms of the downstream aortic remodeling.
      Between 2005 and 2017, 50 patients underwent total arch replacement for Stanford
      type A aortic dissection, including that with (n = 22) and without FET technique
      (n = 28). We compared distal aortic remodeling in patients who underwent total
      arch replacement with (using a J-Graft open stent graft) or without the
      technique. The false lumen complete thrombosis rate and the ratio of true lumen
      area at three levels of the descending aorta were evaluated post operation. In
      FET group, the diameter and length of the stent graft were 29.0 +/- 3.9 mm and
      70.9 +/- 17.4 mm, respectively. The in-hospital death with and without the FET
      technique was 0 and 3, respectively, with no late death in both groups. Eight
      patients (28.6%) only in the non-FET group required additional surgical treatment
      for downstream aorta. In the FET group, the ratio of true lumen area at the level
      of bronchial carina and false lumen complete thrombosis rate at the levels of
      bronchial carina and aortic valve were significantly higher than non-FET group. A
      more favorable remodeling in the descending aorta was observed in patients who
      underwent FET associated with a total arch replacement compared to those who
      underwent total arch replacement alone.

PMID- 30191319
TI  - DIZZYNET 2018: visions and perspectives of future vestibular research.

PMID- 30191320
TI  - Quantitative muscle MRI and ultrasound for facioscapulohumeral muscular
      dystrophy: complementary imaging biomarkers.
AB  - OBJECTIVE: To assess the overlap of and differences between quantitative muscle
      MRI and ultrasound in characterizing structural changes in leg muscles of
      facioscapulohumeral muscular dystrophy (FSHD) patients. METHODS: We performed
      quantitative MRI and quantitative ultrasound of ten leg muscles in 27 FSHD
      patients and assessed images, both quantitatively and visually, for fatty
      infiltration, fibrosis and edema. RESULTS: The MRI fat fraction and ultrasound
      echogenicity z-score correlated strongly (CC 0.865, p < 0.05) and both correlated
      with clinical severity (MRI CC 0.828, ultrasound CC 0.767, p < 0.001). Ultrasound
      detected changes in muscle architecture in muscles that looked normal on MRI. MRI
      was better in detecting late stages of fatty infiltration and was more suitable
      to assess muscle edema. Correlations between quantitative and semi-quantitative
      scores were strong for MRI (CC 0.844-0.982, p < 0.05), and varied for ultrasound
      (CC 0.427-0.809, p = 0.026-p < 0.001). CONCLUSIONS: Quantitative muscle MRI and
      ultrasound are both promising imaging biomarkers for differentiating between
      degrees of structural muscle changes. As ultrasound is more sensitive to detect
      subtle structural changes and MRI is more accurate in end stage muscles and
      detecting edema, the techniques are complementary. Hence, the choice for a
      particular technique should be considered in light of the trial design.

PMID- 30191321
TI  - Toward sustainable solid waste minimization by manufacturing firms in Malaysia:
      strengths and weaknesses.
AB  - Malaysia is facing an increasing trend in industrial solid waste generation due
      to industrial development. Thus, there is a paramount need in taking practical
      actions and measurements to move toward sustainable industrial waste management.
      The main aim of this study is to assess practicing solid waste minimization by
      manufacturing firms. Analysis showed that majority of firms (92%) dispose of
      their wastes rather than utilize other sustainable waste management options.
      Also, waste minimization methods such as segregation of wastes, on-site recycle
      and reuse, improved housekeeping, and equipment modification were found to have
      significant contribution to waste reduction (p < 0.05). Lack of expertise (M =
      3.50), lack of enough information (M = 3.54), lack of equipment modification (M =
      3.16), and lack of specific waste minimization guidelines (M = 3.49) have higher
      mean score comparing with other barriers in different categories. These data were
      interpreted for elaborating on SWOT and TOWS (strengths, weaknesses, threats, and
      opportunities) matrix to highlight strengths, weaknesses, threats, and
      opportunities. Subsequently, ten policies were recommended for improvement of
      practicing waste minimization by manufacturing firms as the main objective of
      this research.

PMID- 30191323
TI  - Engineered 3D tumour model for study of glioblastoma aggressiveness and drug
      evaluation on a detachably assembled microfluidic device.
AB  - 3D models of tumours have emerged as an advanced technique in pharmacology and
      tumour cell biology, in particular for studying malignant tumours such as
      glioblastoma multiforme (GBM). Herein, we developed a 3D GBM model on a
      detachably assembled microfluidic device, which could be used to study GBM
      aggressiveness and for anti-GBM drug testing. Fundamental characteristics of the
      GBM microenvironment in terms of 3D tissue organisation, extracellular matrices
      and blood flow were reproduced in vitro by serial manipulations in the integrated
      microfluidic device, including GBM spheroid self-assembly, embedding in a
      collagen matrix, and continuous perfusion culture, respectively. We could realize
      multiple spheroids parallel manipulation, whilst, compartmentalized culture, in a
      highly flexible manner. This method facilitated investigations into the
      viability, proliferation, invasiveness and phenotype transition of GBM in a 3D
      microenvironment and under continuous stimulation by drugs. Anti-invasion effect
      of resveratrol, a naturally isolated polyphenol, was innovatively evaluated using
      this in vitro 3D GBM model. Temozolomide and the combination of resveratrol and
      temozolomide were also evaluated as control. This scalable model enables research
      into GBM in a more physiologically relevant microenvironment, which renders it
      promising for use in translational or personalised medicine to examine the impact
      of, or identify combinations of, therapeutic agents.

PMID- 30191322
TI  - Indicators of exposure to estrogenic compounds at Great Lakes Areas of Concern:
      species and site comparisons.
AB  - Adverse effects resulting from potential exposure of wild fishes to estrogenic
      endocrine disruptors were assessed at seven United States Great Lakes Areas of
      Concern using biomarkers ranging from organismal (gonadosomatic indices) to
      tissue/plasma (histology, plasma vitellogenin) and molecular (hepatic gene
      transcripts) levels. Biomonitoring was conducted on pelagic, top predator
      species, largemouth Micropterus salmoides and smallmouth M. dolomieu bass and
      benthic, omnivorous white sucker Catostomus commersonii. Seasonal (spring and
      fall) comparisons were conducted at select sites. Intersex (testicular oocytes),
      plasma vitellogenin, and hepatic vitellogenin transcripts were commonly observed
      in bass species. Testicular oocyte severity was positively, although weakly,
      correlated with plasma vitellogenin, hepatic transcripts of vitellogenin,
      estrogen receptor alpha, and estrogen receptor beta2, while negatively correlated
      with androgen receptor beta and phosphoenolpyruvate carboxykinase. No testicular
      oocytes were observed in white sucker; however, plasma vitellogenin and hepatic
      vitellogenin transcripts were commonly detected in the males. The results
      demonstrate the importance of utilizing multiple endpoints to assess exposure to
      estrogenic compounds as well as the importance of choosing sensitive species.

PMID- 30191324
TI  - The influence of correlation on (de)localization indices from a valence bond
      perspective.
AB  - When going beyond the Hartree-Fock level to correlated methods, one observes a
      significant reduction in the delocalization index. This is commonly interpreted
      as a weakening of electron sharing due to electron correlation, although this is
      rather counter-intuitive to the concomitant energy lowering. In this study, we
      use an analytical valence bond model and full CI calculations to show that this
      reduction in the delocalization index actually goes hand in hand with increased
      covalent contributions at the expense of ionic contributions. This suggests that
      we should be careful in formulating interpretations of these results in
      (de)localization indices. Graphical Abstract Variation of the localization
      Delta(OmegaA, OmegaA) and delocalization index Delta(OmegaA, OmegaB) as a
      function of the parameter omega. By adjusting this parameter omega from [Formula:
      see text] to 0, we can gradually change the underlying wave function from a
      Hartree-Fock to a Heitler-London description.

PMID- 30191325
TI  - Evaluation of different samplers and storage temperature effect on the methane
      carbon stable isotope analysis.
AB  - The present work evaluates the efficiency of some low-cost sampler container for
      a reliable carbon stable isotope analysis of methane. The procedure efficiency
      was evaluated for five containers, through 91 days, under two storage
      temperatures (4  degrees C and 25  degrees C) and the results are compared
      against a reference sampler by using univariate and multivariate statistical
      methods. Based on the univariate (ANOVA and comparison statistical methods) and
      multivariate (PCA and HCA) statistical methods, it was identified that (i) the
      isotopic value changes with time and, in this way, must be taken in account when
      choosing the appropriate sampler and (ii) the lower temperature reduces the
      isotopic fractionation process and is preferable for the gas sample storage.
      Among the storage systems, two options were found to be statistically equivalent
      to the reference container (IsoJar) for a time horizon of 91 days. We found that
      the exetainer (4  degrees C and 25  degrees C) storage systems are statistically
      equivalent to the reference container IsoJar and, in this way, it could be an
      alternative for the methane isotopic studies.

PMID- 30191326
TI  - Identification of saprophytic and allergenic fungi in indoor and outdoor
      environments.
AB  - The airborne spores of some saprophytic and allergenic fungi such as Aspergillus,
      Alternaria, and Cladosporium are found throughout the world and exposure to these
      agents may result in various types of allergic diseases. The aim of this study,
      therefore, was to investigate the frequency of different saprophytic, allergenic,
      and pathogenic fungi in indoor and outdoor environments. During a 6-month period,
      780 samples were obtained from a number of houses, mosques, parks, public
      restrooms, grocery stores, laboratories, and hospitals. An open-plate method was
      applied for air sampling by exposing 90-mm plates containing
      chloramphenicol/potato dextrose agar and malt extract agar were exposed to air
      for 30 min. Alternatively, the sampling from surfaces was performed using sterile
      wet swab and tape-stripe method. All samples were then inoculated in media and
      incubated at 28  degrees C for 2-3 weeks. The isolated fungi were purified in
      order to detect the genus, and if possible, species level of the targeted fungi
      based on morphological and microscopic features using standard methods. The
      findings revealed that the dominant indoor and outdoor fungal species were
      Aspergillus, Penicillium, and Cladosporium whose frequency values were 16.42%,
      16.17%, and 14.92% respectively. The lowest frequency was related to
      Acrophialophora and Madurella (0.25%). More notably, the results for air and
      surface were similar. It was also found out that the three dominant genera were
      Aspergillus (16.53%), Penicillium (15.50%), and Cladosporium (11.93%), with
      Basidiobolus and Acrophialophora having the lowest frequency. It was observed
      that different environmental spaces have a great bearing on the spreading of such
      allergic agents, especially in subtropical humid climates.

PMID- 30191327
TI  - Is depression associated with oral health outcomes in adults and elders? A
      systematic review and meta-analysis.
AB  - OBJECTIVES: To systematically review the literature in order to investigate
      association between depression and oral diseases. MATERIAL AND METHODS:
      Electronic searches were performed in five databases. Studies testing
      associations between depression and oral diseases as either exposure or outcome
      were included. Oral disease variable included any tooth loss or edentulism,
      periodontal disease, and dental caries. RESULTS: A total of 2504 articles were
      identified in the electronic database search. Sixteen studies were included in
      this systematic review being 14 included in the meta-analyses. Eleven studies
      considered oral health as outcome, whereas three studies considered depression as
      an outcome variable. Depression was associated to dental caries, tooth loss, and
      edentulism. Pooled estimates showed that depression increased the odds of dental
      caries (OR 1.27; 95% CI 1.13-1.44), tooth loss (OR 1.31; 95% CI 1.24-1.37), and
      edentulism (OR 1.17; 95% CI 1.02-1.34), respectively. When the oral diseases were
      tested as independent variable and depression as outcome, associations with both
      edentulism (OR 1.28; 95% CI 1.06-1.55) and periodontal disease (HR 1.73; 95% CI
      1.58-1.89) were found. CONCLUSIONS: The results of our systematic review and meta
      analyses show a positive association between depression and oral diseases,
      specifically dental caries, tooth loss, and edentulism, in adults and elders.
      More longitudinal studies are required to test causal and temporal relationship
      between depression and oral health status. CLINICAL RELEVANCE: Mental and oral
      health are among the main disabilities worldwide. This article helps to
      understand more about the relationship between both conditions, highlighting the
      importance for both clinicians and policy makers of considering individual's
      psychological status in management of oral health.

PMID- 30191329
TI  - Modeling Sex Differences in Anti-inflammatory Effects of Dexamethasone in
      Arthritic Rats.
AB  - PURPOSE: Collagen-induced arthritic (CIA) rats are used commonly for preclinical
      pharmacologic research into rheumatoid arthritis (RA). Dexamethasone (DEX), a
      potent corticosteroid (CS), remains an important component in combination therapy
      for RA. Although sex differences in RA and CS pharmacokinetics/pharmacodynamics
      (PK/PD) have been documented in humans, there has been no such comprehensive
      evaluation of sex differences in CIA rats. METHODS: Paw size measurements were
      obtained for males and females from four groups of animals: healthy controls, non
      drug treated arthritic animals, and both 0.225 and 2.25 mg/kg DEX-treated
      arthritic animals. A turnover model for disease progression, minimal PBPK model
      for drug concentrations, and inhibitory indirect response model were applied
      using population PK/PD modeling. RESULTS: The clearances of DEX were 43% greater
      in males, but other PK parameters were similar. The temporal profiles of paw
      swelling exhibited earlier progression, peak edema times, and disease remission
      in females. DEX suppressed paw edema well in both males and females with similar
      capacity (Imax) values (=1.0), but DEX potency was less in females with higher
      IC50 values (0.101 versus 0.015 ng/mL). CONCLUSIONS: The pharmacology of DEX was
      well characterized in CIA rats. This study addresses knowledge gaps about sex
      differences and can be a guide for more mechanistic assessment of sex, drug, and
      disease differences in RA.

PMID- 30191328
TI  - Selective Inhibition on Organic Cation Transporters by Carvedilol Protects Mice
      from Cisplatin-Induced Nephrotoxicity.
AB  - PURPOSE: The organic cation transporters (OCTs) and multidrug and toxin
      extrusions (MATEs), located in the basolateral and apical membrane of proximal
      tubular cells respectively, are crucial determinants of renal elimination and/or
      toxicity of cationic drugs such as cisplatin. The purpose of this study was to
      discover selective OCT inhibitors over MATEs, and explore their potential to
      protect against cisplatin-induced nephrotoxicity that is clinically common.
      METHODS: The inhibition by select compounds on the uptake of the probe substrate
      metformin was assessed in HEK293 cells overexpressing human OCT2, OCT1, MATE1,
      MATE2-K, and mouse Oct2, Oct1, and Mate1. Furthermore, the effects of carvedilol
      on organic cation transporter-mediated cellular and renal accumulation of
      metformin and cisplatin, and particularly the toxicity associated with cisplatin,
      were investigated in HEK293 cells and mice. RESULTS: Five selective OCT
      inhibitors were identified through the screening of forty-one drugs previously
      reported as the inhibitors of OCTs and/or MATEs. Among them, carvedilol showed
      the most selectivity on OCTs over MATEs (IC50: 3.6 MUM for human OCT2, 103 MUM
      for human MATE1 and 202 MUM for human MATE2-K) in the cellular assays in vitro,
      with the selectivity in mice as well. Moreover, carvedilol treatment could
      significantly decrease cisplatin accumulation and ameliorate its toxicity both in
      vitro in cells and in vivo in mouse kidney. CONCLUSIONS: Our data indicate that
      selective inhibition of OCTs by carvedilol may protect from cisplatin-induced
      nephrotoxicity by restraining the cellular entry of cisplatin via OCTs, while
      having no impact on its elimination through MATEs.

PMID- 30191330
TI  - Biochemical characterization of the catecholaldehyde reactivity of L-carnosine
      and its therapeutic potential in human myocardium.
AB  - Oxidative deamination of norepinephrine (NE) and dopamine (DA) by monoamine
      oxidase (MAO) generates the catecholaldehydes 3,4-dihydroxyphenylglycolaldehyde
      (DOPEGAL) and 3,4-dihydroxyphenylacetaldehyde (DOPAL), respectively, and H2O2.
      Catecholaldehydes are highly reactive electrophiles that have been implicated as
      causal factors in the etiology of neurodegenerative diseases and cardiac injury
      from ischemia and diabetes. The reactivity of both catechol and aldehyde groups
      enables the catecholaldehdyes to cross-link proteins and other biological
      molecules. Carnosine is a beta-alanyl-histidine dipeptide found in millimolar
      concentrations in brain and myocardium. It is well known to detoxify aldehydes
      formed from oxidized lipids and sugars, yet the reactivity of carnosine with
      catecholaldehydes has never been reported. Here, we investigated the ability of
      carnosine to form conjugates with DOPAL and DOPEGAL. Both catecholaldehydes were
      highly reactive towards L-cysteine (L-Cys), as well as carnosine; however,
      glutathione (GSH) showed essentially no reactivity towards DOPAL. In contrast,
      GSH readily reacted with the lipid peroxidation product 4-hydroxy-2-nonenal
      (4HNE), while carnosine showed low reactivity to 4HNE by comparison. To determine
      whether carnosine mitigates catecholaldehyde toxicity, samples of atrial
      myocardium were collected from patients undergoing elective cardiac surgery.
      Using permeabilized myofibers prepared from this tissue, mitochondrial
      respiration analysis revealed a concentration-dependent decrease in ADP
      stimulated respiration with DOPAL. Pre-incubation with carnosine, but not GSH or
      L-Cys, significantly reduced this effect (p < 0.05). Carnosine was also able to
      block formation of catecholaldehyde protein adducts in isolated human cardiac
      mitochondria treated with NE. These findings demonstrate the unique reactivity of
      carnosine towards catecholaldehydes and, therefore, suggest a novel and distinct
      biological role for histidine dipeptides in this detoxification reaction. The
      therapeutic potential of carnosine in diseases associated with catecholamine
      related toxicity is worthy of further examination.

PMID- 30191331
TI  - Dietary L-lysine supplementation altered the content of pancreatic polypeptide,
      enzymes involved in glutamine metabolism, and beta-actin in rats.
AB  - This study investigated the effects of Lys supplementation on serum pancreatic
      polypeptide (PP), glutamine (Gln) levels and the expression of PP, Gln synthetase
      (GlnS), glutaminase (Gls) and beta-actin in different tissues such as pancreas,
      skeletal muscle, liver and kidney in rats. Male Sprague-Dawley rats were fed
      diets containing 7% casein supplemented with either 0% (Control), 1%, 1.5%, 3%
      Lys or 3% Lys with 1.5% Arg for a week. All rats were necropsied for collection
      of blood and tissues. Expression of PP, GlnS, Gls, and beta-actin in tissues were
      determined using Western blotting. The results showed that the rats fed 3%
      supplemental Lys had significantly lower body weight gain (BWG) and food intake
      than the <= 1.5% Lys groups (P < 0.05). Supplementation with >= 1% Lys increased
      serum PP level (P < 0.05), but had no significant effect on pancreatic PP
      abundance (P > 0.05). GlnS expression was significantly lowered in skeletal
      muscle by >= 1.5% supplemental Lys compared to the Control (P < 0.05). The
      expression of Gls in the kidney was increased by the addition of 1.5% Arg to 3%
      Lys diet (P < 0.05). Liver beta-actin significantly increased with both Lys and
      Arg supplementation and muscle beta-actin significantly decreased (P < 0.05) with
      >= 1.5% supplemental Lys. Kidney beta-actin significantly increased with Arg
      supplementation vs 3% Lys alone (P < 0.05). These results showed that dietary
      supplementation with >= 1.5% Lys significantly suppressed GlnS expression in the
      skeletal muscle, which may contribute to the decreased serum Gln levels, and that
      increased serum PP by Lys may be due to suppressed catabolism rather than
      increased synthesis of PP. Lys-induced PP may play a role in reducing food intake
      and BWG.

PMID- 30191332
TI  - Exploring associations between perinatal depression, anxiety, and urinary
      oxytocin levels in Latinas.
AB  - Perinatal depression has been associated with lower oxytocin (OT) levels.
      However, few studies have explored this topic in relation to Latinas who are at
      high risk of perinatal depression. The objective of this study was to explore
      these associations in Latinas. A total of 108 Latinas in the third trimester of
      pregnancy participated in the study. Depression and urinary OT levels were
      assessed in pregnancy and 6 weeks postpartum. Nonparametric tests were
      implemented to test the proposed associations. Results revealed that 28% of the
      participants had probable depression in pregnancy, and 23% at 6 weeks postpartum.
      OT levels significantly decreased from prenatal to postpartum in the whole
      sample; however, participants with probable prenatal depression did not exhibit a
      significant change in OT levels. Participants who were depressed or anxious at 6
      weeks postpartum exhibited persistently higher mean OT levels over time. A
      distinct pattern of higher levels of OT in depressed Latinas suggests that OT
      levels may be an important neuroendocrine factor contributing to depressive and
      anxious symptoms.

PMID- 30191333
TI  - Moving Past the Routine Use of Macrolides-Reviewing the Role of Combination
      Therapy in Community-Acquired Pneumonia.
AB  - PURPOSE OF REVIEW: Despite advances in diagnostic microbiology and sepsis
      management, community-acquired pneumonia (CAP) remains a significant cause of
      morbidity and mortality. Current recommendations regarding the use of beta
      lactams in combination with macrolides published in clinical practice guidelines
      are variable and based on low-quality evidence that is frequently retrospective,
      observational, and heterogeneous in nature. While population-based studies have
      historically suggested improved clinical outcomes with the routine use of
      macrolide combination therapy in hospitalized patients with CAP, emerging
      evidence from recent randomized controlled trials has challenged this practice.
      In this article, we discuss the historical rationale and current evidence for
      combination macrolide therapy in the management of CAP. RECENT FINDINGS: Recent
      randomized controlled trials have assessed the non-inferiority of beta-lactam
      monotherapy compared to beta-lactam/macrolide combination therapy in adult
      patients hospitalized with CAP. Beta-lactam monotherapy was associated with
      equivalent clinical outcomes in patients with mild to moderate CAP. Patients with
      severe CAP managed with beta-lactam monotherapy have demonstrated worse clinical
      outcomes when compared to patients treated with combination therapy. In addition,
      previous beta-lactam exposure prior to hospitalization has not been shown to
      negatively impact outcomes in patients managed with beta-lactam monotherapy in
      the hospital. Current evidence supports the use of beta-lactam monotherapy in
      adult patients hospitalized with mild to moderate CAP. While existing evidence
      supports the use of combination therapy in patients with severe pneumonia,
      further large-scale randomized controlled trials are urgently needed to clarify
      the role of combination therapy in this population.

PMID- 30191334
TI  - Treatment satisfaction following routine outpatient cognitive-behavioral therapy
      of adolescents with mental disorders: a triple perspective of patients, parents
      and therapists.
AB  - The present study investigates treatment satisfaction (TS) rated by multiple
      informants (patient, parent, therapist) following routine outpatient cognitive
      behavioral therapy (CBT) within a large sample (n = 965) of clinically referred
      adolescents aged 11-20 years. Moreover, potential predictors of TS were analyzed
      (patient-related variables, mental disorder characteristics, socio-demographic
      factors and treatment variables). Overall, our results show a high treatment
      satisfaction in patient, parent and therapist ratings, with the therapists being
      the most critical raters (completely/predominantly satisfied: 87.8% in patient,
      92.0% in parent, and 64.0% in therapist ratings). Correlations between the three
      raters were only small to moderate, but statistically significant. Regression
      analysis examining differential effects found that mental disorder
      characteristics (parent- and patient-reported symptoms at post) and treatment
      variables (especially cooperation of patients and parents as rated by therapists)
      explained most of the variance in TS, whereas patient-related or socio
      demographic variables did not emerge as relevant predictors of TS. The amounts of
      explained variance were R adj.2  = 0.594 in therapist rating, R adj.2  = 0.322 in
      patient rating and R adj.2  = 0.203 in parent rating.

PMID- 30191335
TI  - Trajectories of behavior, attention, social and emotional problems from childhood
      to early adulthood following extremely preterm birth: a prospective cohort study.
AB  - To investigate trajectories of behavior, attention, social and emotional problems
      to early adulthood in extremely preterm survivors compared to a term-born
      comparison group. Longitudinal analysis of a prospective, population-based cohort
      of 315 surviving infants born < 26 completed weeks of gestation recruited at
      birth in 1995, from the UK/Republic of Ireland, and a term-born comparison group
      recruited at age 6. The parent-report Strengths and Difficulties Questionnaire
      was completed at age 6, 11, 16 and 19 years. The Total Behavioral Difficulties
      Score was 4.81 points higher in extremely preterm individuals compared to their
      term-born peers over the period (95% CI 3.76-5.87, p < 0.001) and trajectories
      were stable in both groups. The impact of difficulties on home life, friendships,
      school or work and/or leisure activities was greater in the EPT group (RR 4.28,
      95% CI 2.89-6.35, p < 0.001), and hyperactivity/inattention and peer problems
      accounted for the largest differences. A clinically significant behavioral screen
      at age 2.5 was associated with a higher Total Behavioral Difficulties Score from
      6 years onwards in extremely preterm participants (Mean difference 6.90, 95% CI
      5.01-8.70, p < 0.0.01), as was moderate/severe cognitive impairment at last
      assessment (Mean difference: 4.27, 95% CI 2.76-5.77, p < 0.001). Attention,
      social and emotional problems in extremely preterm individuals persist into early
      adulthood with significant impact on daily life. A positive behavioral screen in
      infancy and moderate/severe cognitive impairment are associated with early adult
      outcomes.

PMID- 30191336
TI  - Raf kinase inhibitor protein mediates myocardial fibrosis under conditions of
      enhanced myocardial oxidative stress.
AB  - Fibrosis is a hallmark of maladaptive cardiac remodelling. Here we report that
      genome-wide quantitative trait locus (QTL) analyses in recombinant inbred mouse
      lines of C57BL/6 J and DBA2/J strains identified Raf Kinase Inhibitor Protein
      (RKIP) as genetic marker of fibrosis progression. C57BL/6 N-RKIP-/- mice
      demonstrated diminished fibrosis induced by transverse aortic constriction (TAC)
      or CCl4 (carbon tetrachloride) treatment compared with wild-type controls. TAC
      induced expression of collagen Ialpha2 mRNA, Ki67+ fibroblasts and marker of
      oxidative stress 8-hydroxyguanosine (8-dOHG)+ fibroblasts as well as the number
      of fibrocytes in the peripheral blood and bone marrow were markedly reduced in
      C57BL/6 N-RKIP-/- mice. RKIP-deficient cardiac fibroblasts demonstrated decreased
      migration and fibronectin production. This was accompanied by a two-fold increase
      of the nuclear accumulation of nuclear factor erythroid 2-related factor 2
      (Nrf2), the main transcriptional activator of antioxidative proteins, and reduced
      expression of its inactivators. To test the importance of oxidative stress for
      this signaling, C57BL/6 J mice were studied. C57BL/6 J, but not the C57BL/6 N
      strain, is protected from TAC-induced oxidative stress due to mutation of the
      nicotinamide nucleotide transhydrogenase gene (Nnt). After TAC surgery, the
      hearts of Nnt-deficient C57BL/6 J-RKIP-/- mice revealed diminished oxidative
      stress, increased left ventricular (LV) fibrosis and collagen Ialpha2 as well as
      enhanced basal nuclear expression of Nrf2. In human LV myocardium from both non
      failing and failing hearts, RKIP-protein correlated negatively with the nuclear
      accumulation of Nrf2. In summary, under conditions of Nnt-dependent enhanced
      myocardial oxidative stress induced by TAC, RKIP plays a maladaptive role for
      fibrotic myocardial remodeling by suppressing the Nrf2-related beneficial
      effects.

PMID- 30191337
TI  - Structural and dynamic characterization of human Wnt2-Fzd7 complex using
      computational approaches.
AB  - Wnt and Frizzled (Fzd) family members play crucial roles in the self-renewal of
      tumor-initiating cells. Until now, only a few studies have addressed the distinct
      mechanism of Wnt-Fzd interactions. In this study, we suggest a possible
      interaction mode of Wnt2 with the Fzd7 cysteine-rich domain (CRD)-both of which
      are up-regulated in some types of cancer. A combination of homology modeling,
      molecular docking and molecular dynamics (MD) simulations was carried out to
      study this ligand-receptor complex in great detail. The results demonstrated the
      unique dynamic behavior of Wnt2 upon binding to Fzd7. Interestingly, the beta
      strand content of the C-terminal binding site of Wnt2 was obviously reduced when
      bound to Fzd7 CRD. Moreover, the N-terminal and C-terminal binding sites of Wnt2
      appeared to interact with the C-terminal and N-terminal binding sites of Fzd7,
      respectively. Calculation of the binding energies uncovered the pivotal role of
      electrostatic and hydrophobic interactions in the binding of Wnt2 to Fzd7 CRD. In
      conclusion, this study provides valuable insights into the mechanism of the Wnt2
      Fzd7 CRD interaction for application in colorectal cancer prevention programs.
      Graphical abstract Flowchart representation of different steps used in this
      study.

PMID- 30191339
TI  - A systematic review of randomised clinical trials for oral antibiotic treatment
      of acute pyelonephritis.
AB  - There is increasing resistance to the oral antibiotics currently recommended for
      the treatment of pyelonephritis, and increased healthcare costs are associated
      with the reliance on alternative intravenous agents. We, therefore, performed a
      systematic review of randomised controlled trials to determine the clinical
      efficacy and safety of oral antibiotics for the treatment of pyelonephritis in
      adults. A search of four major medical databases (MEDLINE, Embase+ Embase
      classic, CENTRAL and Cochrane Database for Systematic Reviews) in addition to
      manual reference searching of relevant reviews was conducted. Clinical cure and
      adverse event rates were reported, and trial quality and bias were assessed. A
      total of 277 studies were reviewed; five studies matched all eligibility criteria
      and were included. Antibiotics included were cefaclor, ciprofloxacin,
      gatifloxacin, levofloxacin, lomefloxacin, loracarbef, norfloxacin, rufloxacin and
      trimethoprim-sulfamethoxazole. In included studies, the clinical success of the
      outpatient treatment of pyelonephritis by cefaclor, ciprofloxacin and norfloxacin
      at 4 to 6 weeks was comparable at between 83 to 95%. Relatively high rates of
      adverse events were noted in a trial of ciprofloxacin (24%) and trimethoprim
      sulfamethoxazole (33%). Significant heterogeneity between all aspects of the
      trial designs was identified, with all studies having a potential for bias. This
      review demonstrates a need for high-quality clinical trials into the oral
      antibiotic treatment of pyelonephritis, with more consistent designs and
      reporting of outcomes. There are data to support further research into oral
      norfloxacin and cefaclor for the outpatient treatment of pyelonephritis in
      adults.

PMID- 30191338
TI  - Is conservative surgery a better choice for the solid/multicystic ameloblastoma
      than radical surgery regarding recurrence? A systematic review.
AB  - PURPOSE: Determine if conservative surgery of primary solid/multicystic
      ameloblastoma (SMA) is capable of decreasing the recurrence rate as effectively
      as radical surgery. METHODS: We searched in MEDLINE, Web of Science, Scopus and
      Cochrane Library for original studies reporting on the conservative or radical
      treatment of primary SMA and the related recurrence rate. All selected data were
      independently assessed. Meta-analysis was performed and the Relative Risk (RR) of
      recurrence with a confidence interval of 95% was the effect measure. P value for
      the summary effect of < 0.05 was considered statistically significant. RESULTS:
      The 2647 records retrieved were reduced to 7 studies to be qualitatively assessed
      and 4 studies were included in the meta-analysis. RR of 1.88 [0.59, 5.95] of the
      pooled values pointed that recurrence rate after the conservative surgery is
      neither comparable nor lower than the radical surgery (P = 0.28). CONCLUSIONS:
      Conservative surgery does not reduce the recurrence rate as efficiently as
      radical surgery for primary SMA. However, there is not enough evidence to support
      this statement.

PMID- 30191342
TI  - Impact of late and prolonged working life on subjective health: the Swedish
      experience.
AB  - This paper explores the relationship between the prolongation of working life and
      subjective health. Drawing on a unique combination of longitudinal data and the
      results of a postal survey in Sweden, we investigate the health consequences of
      extending working life beyond the normal retirement age of 65. To do this, we
      compare the health status of two groups of retired people: one group who left the
      labour market completely at the age of 65, and a second group who remained in
      employment after the age of 65. Using a standard linear probability model and
      controlling for a range of socio-economic variables as well as previous labour
      market experiences, perceived life expectancy, pre-retirement income and health,
      our estimations show that those continuing to work after 65 on average display a
      6.8% higher probability of reporting better health during retirement than those
      leaving at the age of 65. However, we find that this positive correlation between
      the extension of working life and health is only transitory. After 6 years of
      retirement, the health advantage of working after the normal retirement age
      disappears. Furthermore, we did not find any evidence that working after the age
      of 65 is positively correlated with physical fitness, self-reported depressive
      symptoms or well-being.

PMID- 30191340
TI  - A comparison of SensititreTM Anaerobe MIC plate with ATB ANA(r) test for the
      routine susceptibility testing of common anaerobe pathogens.
AB  - The accuracy of the Thermo ScientificTM SensititreTM Anaerobe MIC plate was
      assessed against the ATB ANA(r) test (bioMerieux) on 56 clinically relevant
      anaerobic strains collected at Geneva University Hospitals. The overall
      categorical agreement between both methods reached 95%. The SensititreTM Anaerobe
      MIC plate had excellent accuracy for most antibiotics tested. When the
      SensititreTM Anaerobe MIC plate disagreed with ATB ANA(r) test, the gradient
      strip method resolved the antimicrobial susceptibility categories of all the
      antibiotics tested, except for piperacillin, piperacillin-tazobactam, and
      penicillin, in favor of the SensititreTM Anaerobe MIC plate (58% [21 out of 36]).
      Several very major errors were observed for piperacillin (12.5% [7 out of 56]),
      piperacillin-tazobactam (12.5% [7 out of 56]), and penicillin (2% [1 out of 56]).
      The gradient strip method revealed that the categorical differences for
      piperacillin, piperacillin-tazobactam, and penicillin were at least partly
      explained by heterogeneity in resistance expression. The SensititreTM Anaerobe
      MIC plate offers therefore a useful alternative to the ATB ANA(r) test for the
      routine antimicrobial susceptibility testing of anaerobes in clinical
      microbiology laboratories.

PMID- 30191343
TI  - Blue laser imaging with acetic acid enhancement improved the detection rate of
      gastric intestinal metaplasia.
AB  - Our aim was to evaluate the ability of blue laser imaging (BLI) combined with
      acetic acid (BLI-AA) to detect gastric intestinal metaplasia (GIM). Participants
      undergoing gastroscopy from July 2017 to February 2018 in our hospital were
      enrolled prospectively. The abilities of white light imaging endoscopy, BLI
      endoscopy, and BLI-AA to detect GIM were compared. One hundred six patients
      undergoing gastroscopy met the inclusion criteria. GIM was diagnosed in 41
      patients. For BLI-AA, the sensitivity, specificity, positive predictive, and
      negative predictive values were 85.4%, 84.6%, 77.8%, and 90.2% respectively. The
      diagnostic accuracy rate for BLI-AA was 84.9%, which was higher than that of
      white light imaging endoscopy and BLI endoscopy. For target biopsy, the GIM
      detection rate for the BLI-AA mode was significantly higher (77.8%, 105/135) than
      that for the BLI mode (58.3%, 84/144) or the white light endoscopy mode (40.4%,
      57/141) (p < 0.05). BLI-AA is an efficient and simple method for the detection of
      GIM.

PMID- 30191341
TI  - In Vivo Predictive Dissolution and Simulation Workshop Report: Facilitating the
      Development of Oral Drug Formulation and the Prediction of Oral Bioperformance.

PMID- 30191344
TI  - Simultaneous slice excitation for accelerated passive marker tracking via phase
      only cross correlation (POCC) in MR-guided needle interventions.
AB  - OBJECTIVE: To accelerate a passive tracking sequence based on phase-only cross
      correlation (POCC) using simultaneous slice excitation. METHODS: For magnetic
      resonance (MR)-guided biopsy procedures, passive markers have been proposed that
      can be automatically localized online using a POCC-based tracking sequence. To
      accelerate the sequence, a phase-offset multiplanar (POMP) excitation technique
      was implemented to acquire tracking images. In a phantom experiment, the POMP
      POCC sequence was tested and compared with the sequential non-accelerated version
      in terms of duration and accuracy. Further, technical feasibility of the POMP
      POCC sequence was tested in a patient undergoing a prostate biopsy. RESULTS: The
      temporal resolution of the POMP-POCC tracking sequence is accelerated by 33%
      compared with the sequential approach. In phantom experiments, the POMP-POCC and
      sequential sequences yielded the same targeting accuracy of 1.6 +/- 0.7 mm.
      Technical proof of concept of the new sequence could be demonstrated in a
      successful in vivo prostate biopsy. CONCLUSION: POMP-POCC tracking can
      substantially reduce the duration of localization of passive markers in MR-guided
      needle interventions without compromising targeting accuracy.

PMID- 30191345
TI  - 3D SASHA myocardial T1 mapping with high accuracy and improved precision.
AB  - PURPOSE: To improve the precision of a free-breathing 3D saturation-recovery
      based myocardial T1 mapping sequence using a post-processing 3D denoising
      technique. METHODS: A T1 phantom and 15 healthy subjects were scanned on a 1.5 T
      MRI scanner using 3D saturation-recovery single-shot acquisition (SASHA) for
      myocardial T1 mapping. A 3D denoising technique was applied to the native T1
      weighted images before pixel-wise T1 fitting. The denoising technique imposes
      edge-preserving regularity and exploits the co-occurrence of 3D spatial gradients
      in the native T1-weighted images by incorporating a multi-contrast Beltrami
      regularization. Additionally, 2D modified Look-Locker inversion recovery (MOLLI)
      acquisitions were performed for comparison purposes. Accuracy and precision were
      measured in the myocardial septum of 2D MOLLI and 3D SASHA T1 maps and then
      compared. Furthermore, the accuracy and precision of the proposed approach were
      evaluated in a standardized phantom in comparison to an inversion-recovery spin
      echo sequence (IRSE). RESULTS: For the phantom study, Bland-Altman plots showed
      good agreement in terms of accuracy between IRSE and 3D SASHA, both on non
      denoised and denoised T1 maps (mean difference -1.4 +/- 18.9 ms and -4.4 +/- 21.2
      ms, respectively), while 2D MOLLI generally underestimated the T1 values (69.4 +/
      48.4 ms). For the in vivo study, there was a statistical difference between the
      precision measured on 2D MOLLI and on non-denoised 3D SASHA T1 maps (P = 0.005),
      while there was no statistical difference after denoising (P = 0.95). CONCLUSION:
      The precision of 3D SASHA myocardial T1 mapping was substantially improved using
      a 3D Beltrami regularization based denoising technique and was similar to that of
      2D MOLLI T1 mapping, while preserving the higher accuracy and whole-heart
      coverage of 3D SASHA.

PMID- 30191348
TI  - Novel applications of Machine Learning in cheminformatics.

PMID- 30191347
TI  - Alpha-fetoprotein-producing rectal cancer successfully responded to preoperative
      chemoradiotherapy: case report.
AB  - BACKGROUND: Alpha-fetoprotein (AFP) is produced by some tumors, such as
      hepatocellular carcinoma and yolk sac tumors, leading to an increase in serum AFP
      level. However, AFP in colorectal cancer is extremely rare. Treatment for AFP
      producing cancer is often performed according to conventional methods, but
      oncological outcomes of both surgery and chemotherapy are poor. We report a case
      of a patient with AFP-producing rectal cancer which successfully responded to
      preoperative chemoradiotherapy. CASE PRESENTATION: Rectal tumor was diagnosed in
      a 68-year-old man referred to our hospital. Colonoscopy showed a type 2 tumor in
      the lower rectum, and biopsy revealed an adenocarcinoma with enteroblastic
      differentiation. Serum tumor marker levels were 8.8 ng/ml in carcinoembryonic
      antigen (CEA) and 28.3 ng/ml in AFP. Clinical diagnosis was stage IIIB (T3N1M0),
      and preoperative chemoradiotherapy was performed to prevent local recurrence.
      Effective tumor reduction was observed, and serum tumor marker levels decreased
      to normal range. Low anterior resection with temporary diverting ileostomy was
      performed, and histology revealed residual adenocarcinoma. Pathological diagnosis
      was stage I (T2N0M0). The tumor was found to be an AFP-producing adenocarcinoma
      on further immunohistopathological examination. The postoperative course was
      uneventful, and the patient received adjuvant chemotherapy for 3 months.
      CONCLUSIONS: The outcomes of preoperative chemoradiotherapy against AFP-producing
      rectal cancer are reported here for the first time. Based on our experience with
      this patient, it appears preoperative chemoradiotherapy for patients with AFP
      producing advanced rectal cancer is feasible.

PMID- 30191346
TI  - Functional analysis and clinical significance of sodium iodide symporter
      expression in gastric cancer.
AB  - BACKGROUND: Recent studies have described important roles for the sodium iodide
      symporter (NIS) in tumor behavior. The objectives of the present study were to
      investigate the role of NIS in the regulation of genes involved in tumor
      progression and the clinicopathological significance of its expression in gastric
      cancer (GC). METHODS: In human GC cell lines, knockdown experiments were
      conducted using NIS siRNA, and the effects on proliferation, survival, and
      cellular movement were analyzed. The gene expression profiles of cells were
      examined using a microarray analysis. An immunohistochemical analysis was
      performed on 145 primary tumor samples obtained from GC patients. RESULTS: NIS
      was strongly expressed in MKN45 and MKN74 cells. The depletion of NIS inhibited
      cell proliferation, migration, and invasion and induced apoptosis. The results of
      the microarray analysis revealed that various interferon (IFN) signaling-related
      genes, such as STAT1, STAT2, IRF1, and IFIT1, were up-regulated in NIS-depleted
      MKN45 cells. Furthermore, the down-regulation of NIS affected the phosphorylation
      of MAPKs and NF-kB. Immunohistochemical staining showed that NIS was primarily
      located in the cytoplasm or cell membranes of carcinoma cells, and its expression
      was related to the histological type or venous invasion. Prognostic analyses
      revealed that the strong expression of NIS was associated with shorter
      postoperative survival. CONCLUSIONS: These results suggest that NIS regulates
      tumor progression by affecting IFN signaling, and that its strong expression is
      related to a worse prognosis in patients with GC. These results provide an
      insight into the role of NIS as a mediator and/or a biomarker for GC.

PMID- 30191349
TI  - Ex vivo modelling of the formation of inflammatory platelet-leucocyte aggregates
      and their adhesion on endothelial cells, an early event in sepsis.
AB  - Septicaemia is an acute inflammatory reaction in the bloodstream to the presence
      of pathogen-associated molecular patterns. Whole blood stimulation assays capture
      endotoxin-induced formation of aggregates between platelets and leucocytes using
      flow cytometry. We wanted to assess extent of spontaneous aggregate formation in
      whole blood stimulation assays and compare the effects of endotoxin and heat
      killed, clinically relevant, bacterial pathogens on aggregate formation and then
      on adhesion of aggregates to TNFalpha-stimulated endothelial cells. We found that
      endotoxin (from Escherichia coli or Salmonella enteritidis) was not a suitable
      stimulus to provoke platelet-leucocyte aggregates in vitro, as it did not further
      increase the extent of aggregates formed spontaneously in stasis of hirudin
      anticoagulated blood. Specifically, whole blood samples stimulated with or
      without LPS produced aggregates with a mean surface area of 140.97 and 117.68
      MUm2, respectively. By contrast, incubation of whole blood with heat-killed
      Klebsiella pneumoniae or Staphylococcus aureus produced significantly enhanced
      and complex cellular aggregates (with a mean surface area of 470.61 and 518.39
      MUm2, respectively) which adhered more frequently to TNFalpha (and free fatty
      acid)-stimulated endothelial cells. These were reliably captured by scanning
      electron microscopy. Adhesion of cellular aggregates could be blocked by
      incubation of endothelial cells with a commercial P-selectin antibody and an
      angiopoietin-2 ligand trap. In conclusion, we have developed an in vitro method
      that models the acute inflammatory reaction in whole blood in the presence of
      sepsis-relevant bacterial pathogen surfaces.

PMID- 30191350
TI  - Functional decline of sweet taste sensitivity of colobine monkeys.
AB  - For many primates, sweet taste is palatable and is an indicator that the food
      contains carbohydrates, such as sugars and starches, as energy sources. However,
      we have found that Asian colobine monkeys (lutungs and langurs) have low
      sensitivity to various natural sugars. Sweet tastes are recognized when compounds
      bind to the sweet taste receptor TAS1R2/TAS1R3 in the oral cavity; accordingly,
      we conducted a functional assay using a heterologous expression system to
      evaluate the responses of Javan lutung (Trachypithecus auratus) TAS1R2/TAS1R3 to
      various natural sugars. We found that Javan lutung TAS1R2/TAS1R3 did not respond
      to natural sugars such as sucrose and maltose. We also conducted a behavioral
      experiment using the silvery lutung (Trachypithecus cristatus) and Hanuman langur
      (Semnopithecus entellus) by measuring the consumption of sugar-flavored jellies.
      Consistent with the functional assay results for TAS1R2/TAS1R3, these Asian
      colobine monkeys showed no preference for sucrose or maltose jellies. These
      results demonstrate that sweet taste sensitivity to natural sugars is low in
      Asian colobine monkeys, and this may be related to the specific feeding habits of
      colobine monkeys.

PMID- 30191351
TI  - PET imaging of chemokine receptor CXCR4 in patients with primary and recurrent
      breast carcinoma.
AB  - BACKGROUND: CXCR4 is a chemokine receptor frequently overexpressed in invasive
      breast cancer that has been shown to play a major role in signaling pathways
      involved in metastasis. The aim of this retrospective analysis was to assess the
      diagnostic performance of CXCR4-directed PET imaging in patients with breast
      cancer using the recently introduced CXCR4-targeted PET probe 68Ga-Pentixafor.
      RESULTS: Thirteen patients with first diagnosis of breast cancer, four patients
      with recurrent disease after primary breast cancer, and one patient with axillary
      lymph node metastasis of unknown primary underwent CXCR4-targeted PET imaging
      using 68Ga-Pentixafor. Maximum standardized uptake values (SUVmax) and tumor-to
      background (T/B) ratios of tumor lesions were measured and compared with
      pathological prognostic factors and molecular subtypes. 18F-FDG PET/CT images
      were available in 8/18 cases and were compared semi-quantitatively. Comparison
      with CXCR4 expression determined by immunohistochemistry was performed in 7/18
      patients. Nine of 13 primary breast cancers were visually detectable on 68Ga
      Pentixafor PET images (mean SUVmax of 3.0). The visually undetectable lesions
      included both cases of invasive lobular carcinoma (ILC) and two cases of invasive
      carcinoma of no special type (NST) without any hormone receptor and HER2
      expression (triple negative). Metastases of recurrent breast cancer and unknown
      primary cancer were visually detectable in all five cases, exhibiting a mean
      SUVmax of 3.5. 18F-FDG PET demonstrated higher SUVmax in all patients compared to
      68Ga-Pentixafor PET. A correlation between SUVmax obtained from 68Ga-Pentixafor
      PET and prognostic factors including estrogen receptor (ER), progesterone
      receptor (PR), human epidermal growth factor receptor 2 (HER2) status,
      proliferation index, tumor grade, or molecular subtypes was not observed.
      CONCLUSIONS: CXCR4-directed PET imaging in patients with primary and recurrent
      breast cancer is feasible; however, tumor detectability is significantly lower
      compared to 18F-FDG PET. Moreover, we did not find any correlation between
      aforementioned prognostic factors of breast cancer and CXCR4-targeted tracer
      accumulation. Based on these results in a small patient cohort, CXCR4-targeted
      PET imaging does not seem to be suitable as a general diagnostic tool for imaging
      of breast cancer. Future CXCR4 imaging studies should investigate whether this
      modality might be useful in more specific applications, e.g., in therapeutic
      approaches especially under the view of current developments in targeted immune
      cell and immune checkpoint inhibitory therapy.

PMID- 30191353
TI  - Impact of commercial over-reimbursement on hospitals: the curious case of central
      Indiana.
AB  - An employer coalition in Indiana sponsored a study by the Rand Corporation
      examining commercial insurer payments as a percent of Medicare. The employers
      sought to understand why their health care costs were high and increasing. The
      study showed that, on average, their insurer was paying three times what Medicare
      pays for the same services. In this, a follow-up study, we demonstrate that these
      high payments resulted in very high profit margins for central Indiana's major
      health systems, along with elevated costs and poor performance on key efficiency
      measures. We also see indications that hospitals appear to be using aggressive
      revenue cycle management techniques. The paper concludes with a discussion of
      policy issues.

PMID- 30191352
TI  - Adjusted regularization of cortical covariance.
AB  - It is now common to record dozens to hundreds or more neurons simultaneously, and
      to ask how the network activity changes across experimental conditions. A natural
      framework for addressing questions of functional connectivity is to apply
      Gaussian graphical modeling to neural data, where each edge in the graph
      corresponds to a non-zero partial correlation between neurons. Because the number
      of possible edges is large, one strategy for estimating the graph has been to
      apply methods that aim to identify large sparse effects using an [Formula: see
      text] penalty. However, the partial correlations found in neural spike count data
      are neither large nor sparse, so techniques that perform well in sparse settings
      will typically perform poorly in the context of neural spike count data.
      Fortunately, the correlated firing for any pair of cortical neurons depends
      strongly on both their distance apart and the features for which they are tuned.
      We introduce a method that takes advantage of these known, strong effects by
      allowing the penalty to depend on them: thus, for example, the connection between
      pairs of neurons that are close together will be penalized less than pairs that
      are far apart. We show through simulations that this physiologically-motivated
      procedure performs substantially better than off-the-shelf generic tools, and we
      illustrate by applying the methodology to populations of neurons recorded with
      multielectrode arrays implanted in macaque visual cortex areas V1 and V4.

PMID- 30191354
TI  - Construction strategies for developing expression vectors for recombinant
      monoclonal antibody production in CHO cells.
AB  - Recent years have seen the use of recombinant proteins in the treatment of
      different diseases. Among them, monoclonal antibodies (mAbs) are currently the
      fastest growing class of bio-therapeutic recombinant proteins. Chinese hamster
      ovary (CHO) cells are the most commonly used host cells for production of these
      recombinant mAbs. Expression vectors determine the expression level and quality
      of recombinant mAbs. Currently, few construction strategies for recombinant mAbs
      expression vectors in CHO cells have been developed, including monocistronic
      vector, multiple-promoter expression vector, and tricistronic vector mediated by
      internal ribosome entry site (IRES) or Furin-2A element. Among them, Furin-2A
      mediated vector is an effective approach due to advantages of high "self
      cleavage" efficiency, and equal expression of light and heavy chains from a
      single open reading frame. Here, we have reviewed the progress in development of
      different strategies for constructing recombinant mAb expression vectors in CHO
      cells and its potential advantages and disadvantages.

PMID- 30191355
TI  - Synthesis of Symmetric Bridged Bis-Pyrazolone Based Metal Complex Acid Dyes and
      their Applications on Leather.
AB  - Our present investigation aims at the synthesis and application of new, symmetric
      bridged bis-pyrazolone based acid dyes. The bis-pyrazolone compounds were
      accomplished from bis- hydrazine of 4,4'-Diaminostilbene-2,2'-disulfonic acid and
      ethyl acetoacetate. The bis-pyrazolones have been coupled with diazonium salts of
      o-hydroxyl aromatic amines which resulted in ligand dyes. The intermediate ligand
      dyes were treated with 3d transition metals to achieve the targeted metal complex
      acid dyes. The structures of investigated compounds were confirmed with the help
      of spectroscopic techniques. Dyes were applied on leather and their application
      parameters including their light fastness, wash fastness and rubbing fastness
      were determined. Graphical Abstract Symmetric brymmetric Bridged bis-Pyrazolone
      based Metal Complex Acid.

PMID- 30191356
TI  - A Medical Sublime.
AB  - Inspired by a passage from Kate Chopin's The Awakening, this article considers
      the possibility of a "medical sublime." It works through a history of the sublime
      in theory and in the arts, from ancient times to the present. It articulates
      therapeutic dimensions of the sublime and gives contemporary examples of its
      medical relevance. In addition, it develops the concept of sublime-based stress
      reduction workshops and programs. These workshops bring the sublime out of the
      library and the museum into the lives of the healthcare community-patients,
      families, clinicians, staff, concerned others-in the service of better navigating
      human vulnerability and finitude. Opening the cannon of aesthetic theory and the
      arts as resources for the human condition is at the heart of health humanities.
      The sublime can be an invaluable tool in this task.

PMID- 30191357
TI  - Evaluation of direct oral anticoagulants for the treatment of venous
      thromboembolism in the oncology population.
AB  - Direct oral anticoagulants (DOACs) have become an attractive option for the
      treatment of venous thromboembolism (VTE) in cancer patients. However, their use
      is currently not recommended as first-line treatment by national guidelines due
      to limited data in this patient population. The objective of this study was to
      evaluate the practice and safety patterns of DOACs when used for VTE treatment in
      the oncology population. This study was a retrospective chart review of adult
      cancer patients treated at Hackensack University Medical Center from January 2013
      to October 2015 who received dabigatran, rivaroxaban, or apixaban for VTE
      treatment. Of 126 patients screened, 39 patients were included. Thirty-five
      patients received rivaroxaban and four patients received apixaban. Ten of 39
      patients (26%) were not receiving a DOAC dosage consistent with the package
      insert. No patients experienced clinically significant bleeding, while four
      patients experienced a minor bleed. Four of 14 thrombocytopenic patients (29%)
      did not have their DOAC dose held for thrombocytopenia. All patients had their
      DOACs appropriately held for procedures. Increased education on dosing DOACs
      according to the package insert is warranted for oncology prescribers. Despite
      the increased risk for bleeding in cancer patients, no clinically significant
      bleeding events were identified in our patient cohort. This data suggests that
      the use of DOACs may be safe to use for VTE treatment in cancer patients and may
      provide foundation for larger, randomized controlled trials to determine whether
      DOACs should be used for VTE treatment in cancer patients.

PMID- 30191358
TI  - Using a Polygraph System for Evaluation of the Social Desirability Response Bias
      in Self-Report Measures of Aggression.
AB  - Empirical evidence suggests that respondents systematically overreport socially
      desirable behaviors and systematically underreport socially undesirable
      behaviors. This "social desirability response bias (SDRB)" presents significant
      challenges for research that relies on self-report measures to assess behaviors
      that adhere to or violate social norms. The present study used a state-of-the-art
      polygraph system to examine SDRB in widely used aggression questionnaires,
      including the Buss-Perry Aggression Questionnaire-Short Form, the Indirect
      Aggression subscale of the Aggression Questionnaire by Western Psychological
      Services, and the Reactive-Proactive Questionnaire. Sixteen college students with
      no criminal record, no known prior history of aggressive behavior, and no
      reported drug abuse, responded to verbally administered forms of the instruments.
      Indirect aggression items produced the largest, statistically significant
      physiological response across the sampled channels. The magnitude of this
      response was negatively and significantly correlated with the self-report ratings
      of the frequency of such behaviors. The mean separation between physiological
      (skin conductance) and self-report responses for indirect aggression remained
      significant and consistent with correlational analyses when both types of
      responses were converted to the same scale and compared directly. Finally, the
      relative magnitude of skin conductance response for items assessing indirect
      aggression was significantly greater than the relative magnitude of skin
      conductance response for direct aggression. Overall, the study suggests that the
      use of automated state-of-the art polygraph systems may potentially identify
      sensitive items on self-report instruments where social responsibility response
      bias is possible. Implications for the use of this procedure with such
      instruments are discussed.

PMID- 30191360
TI  - Pazopanib may reduce bleeding in hereditary hemorrhagic telangiectasia.
AB  - Pazopanib (Votrient) is an orally administered tyrosine kinase inhibitor that
      blocks VEGF receptors potentially serving as anti-angiogenic treatment for
      hereditary hemorrhagic telangiectasia (HHT). We report a prospective, multi
      center, open-label, dose-escalating study [50 mg, 100 mg, 200 mg, and 400 mg],
      designed as a proof-of-concept study to demonstrate efficacy of pazopanib on HHT
      related bleeding, and to measure safety. Patients, recruited at 5 HHT Centers,
      required >= 2 Curacao criteria AND [anemia OR severe epistaxis with iron
      deficiency]. Co-primary outcomes, hemoglobin (Hgb) and epistaxis severity, were
      measured during and after treatment, and compared to baseline. Safety monitoring
      occurred every 1.5 weeks. Seven patients were treated with 50 mg pazopanib daily.
      Six/seven showed at least 50% decrease in epistaxis duration relative to baseline
      at some point during study; 3 showed at least 50% decrease in duration during
      Weeks 11 and 12. Six patients showed a decrease in ESS of > 0.71 (MID) relative
      to baseline at some point during study; 3/6 showed a sustained improvement. Four
      patients showed > 2 gm improvement in Hgb relative to baseline at one or more
      points during study. Health-related QOL scores improved on all SF-36 domains at
      Week 6 and/or Week 12, except general health (unchanged). There were 19 adverse
      events (AE) including one severe AE (elevated LFTs, withdrawn from dosing at 43
      days); with no serious AE. In conclusion, we observed an improvement in Hgb
      and/or epistaxis in all treated patients. This occurred at a dose much lower than
      typically used for oncologic indications, with no serious AE. Further studies of
      pazopanib efficacy are warranted.

PMID- 30191361
TI  - Gamma knife radiosurgery for recurrent gliomas.
AB  - OBJECTIVE: In recent years, gamma knife radiosurgery (GKRS) has become
      increasingly more popular as a salvage treatment modality for patients diagnosed
      with recurrent gliomas. The goal of GKRS for recurrent glioma patients is to
      improve survival rates with minimal burden for these patients. The emphasis of
      this report is on local tumor control (TC), clinical outcome and survival
      analysis. METHODS: We performed a retrospective analysis of prospectively
      collected data of all patients who underwent GKRS for gliomas at the Gamma Knife
      Center Tilburg between 23-09-2002 and 21-05-2015. In total, 94 patients with
      glioma were treated with GKRS. Two patients were excluded because GKRS was used
      as a first stage treatment. The other 92 patients were included for analysis.
      RESULTS: TC was 37% for all tumors (TC was 50% in LGGs and 27% in HGGs). Local
      progression (LP) was 46% for all tumors (LP was 31% in LGGs and 58% in HGGs). New
      distant lesions were seen in 18% of all patients (in 5% of LGG patients and 31%
      of HGG patients). Median progression-free and overall survival (PFS and OS) for
      all patients were 10.5 and 34.4 months, respectively. Median PFS was 50.1 and 5.7
      months for low and high grade tumors, respectively. Median OS was 86.6 and 12.8
      months for low and high grade tumors, respectively. No serious adverse events
      were noted post-GKRS. CONCLUSION: GKRS can safely be used as salvage treatment
      for recurrent glioma and seems to improve survival rates in (high grade) glioma
      patients with minimal burden.

PMID- 30191362
TI  - A population based pediatric oncology registry in Southern Sweden: the BORISS
      registry.
AB  - A population based registry, with the acronym BORISS, was established. It
      contains all individuals (0-18 years of age at diagnosis) diagnosed with cancer
      from 1970-01-01 until 2016-12-31 in Southern Sweden. The treatment data has been
      entered into the registry after confirmation of the diagnosis by the Swedish
      national cancer registry and updates on vital status from the Swedish population
      registry. The number of individuals with a pediatric cancer diagnosed during
      these 46 years are 2928. Of these, 2065 are currently alive and 1882 individuals
      are 5-year survivors. Data on treatment and malignancy of the 5-year survivors
      has been collected from medical records and entered into the database. Treatment
      data contains surgical procedure, target organ of radiation therapy including
      dose and fractionation, and cytostatic treatment with dose (mg) per body surface
      area (m2) for all cytostatic agents. Data on individuals receiving stem cell
      treatment is included. The database is unique in that it is population based,
      contains all individuals and detailed treatment data on all 5-year survivors
      after childhood cancer in Southern Sweden since 1970. The database has
      contributed to several academic theses in the field of late effects after
      childhood cancer. BORISS also supports the Late Effect Clinic at Skane University
      Hospital in Lund, Sweden with treatment details enabling a stratified
      surveillance.

PMID- 30191363
TI  - Functional and educational outcomes after treatment for intracranial
      arteriovenous malformations in children.
AB  - BACKGROUND: Arteriovenous malformations (AVMs) in the pediatric population are
      rare, yet they form the most frequent cause of hemorrhagic stroke in children.
      Compared to adults, children have been suggested to have beneficial neurological
      outcomes. However, few studies have focused on other variables than neurological
      outcomes. This study aims to assess the long-term functional and educational
      outcomes of children after multimodality approach of treatment for intracranial
      AVMs. METHODS: All children treated in our center between 1998 and 2016 for
      intracranial AVMs were reviewed. Patient characteristics, as well as AVM
      specifics, were collected. Functional outcomes were compared using the modified
      Rankin scale (mRs). Educational levels, using the International Standard
      Classification of Education (ISCED), were compared to the age-matched general
      population of the Netherlands. RESULTS: In total, 25 children were included at
      mean age of 10 years (range 2-16 years). Nineteen patients (76%) presented with
      intracranial bleeding. Mean follow-up was 11.5 +/- 5.3 years (range 4.1-24.4).
      Four (16%) of patients were treated with embolization, three (12%) with
      microsurgery, and 18 patients (72%) received a combination of different treatment
      modalities. Altogether, 21 (84%) were embolized, 14 (56%) were treated with
      microsurgery, and eight (32%) received stereotactic radiosurgery. One child had a
      worse mRs at discharge compared to admission; all others improved (n = 11) or
      were stable (n = 13). At follow-up, all patients scored a stable or improved mRs
      compared to discharge, with 23 children (92%) scoring mRs 0 or 1. These 23
      children followed regular education during follow-up without specialized or
      adapted schooling. No significant differences in educational level with the age
      matched general population were found. CONCLUSION: This retrospective review
      shows positive long-term results of both functional and educational outcomes
      after multidisciplinary treatment of pediatric brain AVMs.

PMID- 30191364
TI  - Temporal changes in outcome following intensive care unit treatment after
      traumatic brain injury: a 17-year experience in a large academic neurosurgical
      centre.
AB  - BACKGROUND: Traumatic brain injury (TBI) is a major cause of morbidity and
      mortality. However, it remains undetermined whether long-term outcomes after TBI
      have improved over the past two decades. METHODS: We conducted a retrospective
      analysis of consecutive TBI patients admitted to an academic neurosurgical ICU
      during 1999-2015. Primary outcomes of interest were 6-month all-cause mortality
      (available for all patients) and 6-month Glasgow Outcome Scale (GOS, available
      from 2005 onwards). GOS was dichotomized to favourable and unfavourable
      functional outcome. Temporal changes in outcome were assessed using multivariate
      logistic regression analysis, adjusting for age, sex, GCS motor score, pupillary
      light responsiveness, Marshall CT classification and major extracranial injury.
      RESULTS: Altogether, 3193 patients were included. During the study period,
      patient age and admission Glasgow Coma Scale score increased, while the overall
      TBI severity did not change. Overall unadjusted 6-month mortality was 25% and
      overall unadjusted unfavourable outcome (2005-2015) was 44%. There was no
      reduction in the adjusted odds of 6-month mortality (OR 0.98; 95% CI 0.96-1.00),
      but the adjusted odds of favourable functional outcome significantly increased
      (OR 1.08; 95% CI 1.04-1.11). Subgroup analysis showed outcome improvements only
      in specific subgroups (conservatively treated patients, moderate-to-severe TBI
      patients, middle-aged patients). CONCLUSIONS: During the past two decades,
      mortality after significant TBI has remained largely unchanged, but the odds of
      favourable functional outcome have increased significantly in specific subgroups,
      implying an improvement in quality of care. These developments have been
      paralleled by notable changes in patient characteristics, emphasizing the
      importance of continuous epidemiological monitoring.

PMID- 30191365
TI  - Quality-adjusted survival of nivolumab plus ipilimumab or nivolumab alone versus
      ipilimumab alone among treatment-naive patients with advanced melanoma: a quality
      adjusted time without symptoms or toxicity (Q-TWiST) analysis.
AB  - PURPOSE: To compare the quality-adjusted survival of nivolumab plus ipilimumab
      combination and nivolumab alone versus ipilimumab alone among treatment-naive
      patients with advanced melanoma based on a minimum 36-month follow-up from the
      CheckMate 067 trial. METHODS: Overall survival was partitioned into time without
      symptoms of progression or toxicity (TWiST), time with treatment-related grade >=
      3 adverse events after randomization but before progression (TOX), and time from
      progression until end of follow-up or death (REL). Mean quality-adjusted TWiST (Q
      TWiST) was calculated by multiplying the mean time spent in each health state by
      a utility of 1.0 for TWiST and 0.5 for TOX and REL. Sensitivity analyses included
      varying utilities of TOX and REL; Q-TWiST gains at different follow-up times were
      calculated using EQ-5D-3L utilities from the trial. Relative Q-TWiST gain of >=
      10% was considered clinically important. RESULTS: Compared with ipilimumab
      treated patients, those who received nivolumab + ipilimumab combination had
      significantly longer TWiST and TOX but shorter REL; nivolumab-treated patients
      had significantly longer TWiST, shorter REL, and shorter but statistically
      nonsignificant TOX. Mean Q-TWiST was highest for nivolumab + ipilimumab (23.5
      months; 95% CI 21.9-25.2), followed by nivolumab (21.8 months; 95% CI 20.2-23.4)
      and ipilimumab (15.3 months; 95% CI 13.9-16.6). Relative Q-TWiST gains were
      favorable and clinically important for nivolumab + ipilimumab combination (+
      36.81%) and nivolumab alone (+ 29.18%) versus ipilimumab alone. Relative gains
      increased with follow-up from 3 to 40 months for all comparisons. These gains
      remained consistent in magnitude and direction in the different sensitivity
      analyses. CONCLUSIONS: Nivolumab + ipilimumab combination and nivolumab alone
      resulted in a statistically significant and clinically important improvement in
      quality-adjusted survival compared with ipilimumab alone.

PMID- 30191366
TI  - An analysis of allele, genotype and phenotype frequencies, actionable
      pharmacogenomic (PGx) variants and phenoconversion in 5408 Australian patients
      genotyped for CYP2D6, CYP2C19, CYP2C9 and VKORC1 genes.
AB  - Common polymorphisms in the genes encoding CYP2D6, CYP2C19, CYP2C9 and VKORC1
      enzymes have an important role in predicting the occurrence of adverse effects
      and the efficacy of substrate medications. Drug-induced changes to the enzyme's
      phenotype, a process called phenoconversion, comprise another important factor
      contributing to interindividual variability in drug response. To date, there is
      lack of data on the frequency of these common polymorphisms and phenoconversion
      in the pan-ethnic Australian population. The aim of this study was to (1)
      describe allele, genotype and phenotype frequencies for CYP2D6, CYP2C19, CYP2C9
      and VKORC1 enzymes in the pan-ethnic Australian population and (2) evaluate the
      frequency of actionable pharmacogenomic (PGx) variants and phenoconversion.
      Frequencies were calculated using the records of 5408 Australian patients
      (obtained from myDNA's propriety database), who were consecutively tested with
      the DNAdose PGx test which included the CYP2D6, CYP2C19, CYP2C9 and VKORC1 genes.
      In 2509 patients with listed medications at the time of testing, phenoconversion
      frequencies were calculated for CYP2D6, CYP2C19 and CYP2C9 enzymes. Allele,
      genotype and phenotype frequencies in our Australian patients correlated with a
      Caucasian population. Approximately 96% of patients had at least one actionable
      PGx variant. A five-fold increase in the frequency of poor metabolisers (PMs) for
      CYP2D6 and CYP2C19 was predicted by phenoconversion. Our study results indicate a
      high frequency of actionable PGx variants in our Australian population. With the
      addition of drug-induced phenoconversion, our results provide further support for
      the utilisation of PGx testing in clinical practice as another tool assisting
      prescribers in the application of personalised medicine.

PMID- 30191367
TI  - Derivatization of common antidepressant drugs increases inhibition of acid
      sphingomyelinase and reduces induction of phospholipidosis.
AB  - In recent studies, major depressive disorder (MDD) was linked to an increase in
      acid sphingomyelinase (ASM) activity. Several drugs that are commonly used to
      treat MDD functionally inhibit the lysosomal enzyme ASM and are called functional
      inhibitors of ASM (FIASMAs). These drugs are classified as cationic amphiphilic
      drugs (CADs) that influence the catalytic activities of different lysosomal
      enzymes. This action results in the side effect of phospholipidosis (PLD), which
      describes a detrimental increase in the phospholipid content in lysosomes.
      FIASMAs differ only slightly in their physico-chemical properties, but their
      effects on ASM activity and induction of the lysosomal phospholipid content vary
      significantly. In this study, we systematically induced minor chemical
      modifications to the FIASMAs imipramine, desipramine and fluoxetine. We generated
      a library of 45 new CADs with slightly different log P (logarithmic partition
      coefficient) and pKa (logarithmic acid dissociation constant) values. The effects
      of the compounds on the ASM activity and lysosomal phospholipid content were
      assessed in cell culture assays. We identified four compounds with beneficial
      effects, i.e., increased ASM activity inhibition and reduced PLD induction
      compared with the original drugs. The compounds HT04, RH272B and RH272D
      outperformed the original imipramine, whereas RH281A performed better than
      desipramine. Thus, minor chemical variations of CADs impact lysosomal metabolism
      in a specific manner and can lead to antidepressant drugs with less deleterious
      side effects.

PMID- 30191368
TI  - A tandem duplication of BRCA1 exons 1-19 through DHX8 exon 2 in four families
      with hereditary breast and ovarian cancer syndrome.
AB  - PURPOSE: The purpose of this study is to characterize a novel structural variant,
      a large duplication involving exons 1-19 of the BRCA1 gene in four independent
      families, and to provide diagnostically valuable information including the
      position of the breakpoints as well as clues to its clinical significance.
      METHODS: The duplication of exons 1-19 of the BRCA1 gene was initially detected
      by routine laboratory testing including MLPA analysis and next generation
      sequencing. For detailed characterization we performed array-comparative genome
      hybridization analysis, fluorescent in situ hybridization, next generation
      mapping, and long-distance PCR for break-point sequencing. RESULTS: Our data
      revealed a tandem duplication on chromosome 17 that encompassed 357 kb and
      included exons 1-19 of the BRCA1 gene and the genes NBR2, NBR1, TMEM106A,
      LOC100130581, ARL4D, MIR2117 up to parts of the DHX8 gene. This structural
      variant appeared as a tandem duplication with breakpoints in intron 19 of the
      BRCA1 gene and in intron 3 of the DHX8 gene
      (HGVS:chr17(hg19):g.41210776_41568516dup). Segregation analysis indicated that
      this structural rearrangement is phased in trans with a known pathogenic exon
      deletion of the BRCA1 gene in one family. CONCLUSIONS: The copy number variation
      initially recognized as duplication of exon 1-19 of the BRCA1 gene by MLPA
      analysis is a structural variation with breakpoints in the BRCA1 and DHX8 genes.
      Although currently to be classified as a variant of unknown significance, our
      family data indicates that this duplication may be a benign variation or at least
      of markedly reduced penetrance since it occurs in trans with another known fully
      pathogenic variant in the BRCA1 gene.

PMID- 30191369
TI  - Short- and long-term outcomes of robotic-assisted laparoscopic surgery for rectal
      cancer: results of a single high-volume center in Japan.
AB  - PURPOSE: Scientific evidence supporting robotic-assisted laparoscopic surgery
      (RALS) for rectal cancer remains inconclusive because most previous reports were
      retrospective case series or case-control studies, with few reports focusing on
      long-term oncological outcomes with a large volume of patients. The aim of this
      study was to clarify the short- and long-term outcomes of a large number of
      consecutive patients with rectal cancer who underwent RALS in a single high
      volume center. METHODS: The records of 551 consecutive patients who underwent
      RALS for rectal adenocarcinoma between December 2011 and March 2017 were examined
      to reveal the short-term outcomes. The oncological outcomes of the 204 patients
      who underwent surgery between December 2011 and March 2014 were evaluated.
      RESULTS: Most patients had tumors located in the lower or mid-rectum (86.0%).
      Only 7.6% of patients underwent neoadjuvant chemoradiotherapy. Lateral lymph node
      dissection was performed for 191 patients (34.7%). The median operative time was
      257 min, median blood loss was 10 mL, and no transfusions were needed. No
      conversion to open surgery was necessary. Eighteen patients (3.3%) had Clavien
      Dindo grade III postoperative complications. Six patients (1.1%) had positive
      resection margins. The mean follow-up duration of the 204 patients was 43.6 +/-
      9.8 (months). The 5-year cancer-specific survival rate for stage I/II/III/IV was
      100%/100%/100%/not reached, respectively. The 5-year relapse-free survival rate
      for stage I/II/III/IV was 93.6%/75.0%/77.6%/ not reached, respectively. The rate
      of local recurrence was 0.5%. CONCLUSIONS: Our results suggest that RALS is
      technically feasible for rectal cancer and has good short- and long-term
      outcomes.

PMID- 30191370
TI  - Intracorporeal versus extracorporeal anastomosis in right hemicolectomy assisted
      by laparoscopy: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Colorectal cancer (CRC) is the third most frequent cancer diagnosed
      in men and the second in women. Laparoscopic surgery has been a technical
      revolution in colorectal surgery, facilitating a better recovery of patients with
      lower morbidity and better esthetic results, compared to traditional surgery via
      laparotomy, without compromising safety and long-term oncological results.
      PURPOSE: The trial is a randomized controlled trial indented to evaluate the two
      interventions with thorough measurements of the postoperative variables and
      complications to improve the evaluation of the surgical technique. The primary
      endpoint is to compare the hospital stay, which will be measured in days between
      both groups. The purpose of the study at secondary endpoints is to compare
      intraoperative and postoperative events between both groups in terms of operating
      time, anastomotic performance time, intraoperative complications, number of
      harvested lymph nodes, need for blood transfusion, length of the surgical wound,
      start and tolerance of oral intake, beginning of digestive functionality,
      postoperative pain, need for analgesic administration, surgical wound infection,
      paralytic ileus, anastomosis leakage or dehiscence, need for surgical
      reintervention, and hospital readmission within the first 30 days after surgery.
      METHODS: This trial is a prospective, randomized, single-blind, and single-center
      clinical trial comparing intracorporeal anastomosis versus extracorporeal
      anastomosis for right laparoscopic hemicolectomy. CONCLUSIONS: Nowadays, there
      are several retrospective trials comparing the benefits for extracorporeal
      anastomosis versus intracorporeal anastomosis in right colon cancer patients.
      Considering the impact for laparoscopic surgery, we think it is necessary to do a
      randomized trial comparing extracorporeal versus intracorporeal anastomosis
      modalities. TRIAL REGISTRATION: www.clinicaltrials.gov No. NCT02667860 and
      Hospital de la Santa Creu i Sant Pau Research Institute No. IIBSP-AIE-2015-01.

PMID- 30191371
TI  - Bottlenecks and complementation in the aphid transmission of citrus tristeza
      virus populations.
AB  - Aphid transmission is a major factor in the formation of citrus tristeza virus
      (CTV) populations. Here, we examined the effect of population interaction on
      aphid transmissibility of different CTV genotypes. We found that there was no
      correlation between the proportion of viral genotypes in the source population
      and what was transmitted. We next examined the transmission of a poorly
      transmitted infectious cDNA clone (T36) in mixture with other CTV genotypes. T36
      transmission increased from 0.5% alone, to up to 35.7%, depending on the
      coinfecting genotype. These results suggest that interaction between CTV
      genotypes affects the transmission of this virus.

PMID- 30191372
TI  - Molecular characterization of a novel picobirnavirus in a chicken.
AB  - Picobirnaviruses (PBVs) are bisegmented viruses with a wide geographical and host
      species distribution. The number of novel PBV sequences has been increasing with
      the help of the viral metagenomics. A novel picobirnavirus strain,
      pbv/CHK/M3841/HUN/2011, was identified by viral metagenomics; the complete
      segment 1 (MH327933) and 2 (MH327934) sequences were obtained by RT-PCR from a
      cloacal sample of a diseased broiler breeder pullet in Hungary. Although the
      conserved nucleotide (e.g., ribosome binding site) and amino acid motifs (e.g.,
      ExxRxNxxxE, S-domain of the viral capsid and motifs in the RNA-dependent RNA
      polymerase) were identifiable in the chicken picobirnavirus genome, the putative
      segment 1 showed low (< 30%) amino acid sequence identity to the corresponding
      proteins of marmot and dromedary PBVs, while segment 2 showed higher (< 70%)
      amino acid sequence identity to a wolf PBV protein sequence. This is the first
      full-genome picobirnavirus sequence from a broiler breeder chicken, but the
      pathogenicity of this virus is still questionable.

PMID- 30191373
TI  - Performance evaluation of a newly developed molecular assay for the accurate
      diagnosis of gastroenteritis associated with norovirus of genogroup II.
AB  - The performance of a newly proposed fully automated cassette-based sample-to
      results solution for norovirus (NoV) detection, InGenius Norovirus ELITe MGB(r),
      was evaluated. A total of 120 selected archival stool samples from children
      hospitalized for acute gastroenteritis were used to compare the results to a
      reference real-time RT-PCR. The InGenius NoV assay showed optimal diagnostic
      accuracy (sensitivity, 100%; specificity, 95.7%) and was able to correctly detect
      the entire wide panel of epidemiologically relevant genotypes tested. These
      preliminary results suggest that the InGenius NoV assay can be recommended as a
      valuable method for accurate diagnosis of NoV GII infection in epidemic and
      sporadic gastroenteritis.

PMID- 30191375
TI  - Identification of rehmannia virus 1, a novel putative member of the genus
      Closterovirus, from Rehmannia glutinosa.
AB  - Transcriptome sequencing analysis of a symptomatic Rehmannia glutinosa plant
      revealed a virome containing two known RNA viruses and one novel virus. In this
      study, we examined the molecular and biological characteristics of the novel
      virus. The complete genome of the novel virus is composed of monopartite single
      stranded RNA of 15,322 nucleotides with 69% nucleotide sequence identity (with
      68% coverage) to tobacco virus 1. Its genome organization is typical of the
      members of the genus Closterovirus, containing nine putative open reading frames.
      Molecular and phylogenetic analyses of the genome and encoded protein sequences
      strongly support that the identified virus is a new species of the genus
      Closterovirus in the family Closteroviridae. The name rehmannia virus 1 (ReV1) is
      proposed for this novel virus.

PMID- 30191376
TI  - Suicidal head impalement with a hydraulic press machine - occupation-related
      suicide in a psychiatric patient.
AB  - A 63-year-old mechanic, diagnosed with schizophrenia, was found next to a
      hydraulic press used for removing car wheel bearings. He was in a sitting
      position, bent towards the machine, with his head placed between the piston and
      the pressing plate. His flexed left arm was resting on the lever beneath the
      machine pedestal, and on the right side there was a power switch that was still
      in the "on" position. His right arm was beside his body, but away from the
      machine. On the pressing plate, beneath the decedents head, was a piece of bloody
      cloth. Blood spatters were present on the left hand and left trouser leg. At
      autopsy there was a gaping laceration in the right temporal area extending to the
      right ear lobe, where a piece of helix was missing. This missing tissue was found
      on the inner surface of the left temporal bone. The temporal lobes and brain-stem
      were destroyed along the wound trajectory but there were no brain contusions
      present. There was blood aspiration in both lungs, but all other findings were
      unremarkable. Death was attributed to the fatal head injury that resulted from
      the low-velocity penetration of the hydraulic press piston. While the cause of
      death was self-evident and undoubted, the manner of death required medico-legal
      investigation. The protective cloth that had been placed on the pressing plate, a
      medical history of schizophrenia, and the absence of any defensive injuries, all
      led to the conclusion that this was a case of a rather unusual suicide, which
      could be regarded as related to the decedents occupation.

PMID- 30191374
TI  - Development of a serosurveillance assay for detection of Necocli virus exposure.
AB  - Hantavirus cardiopulmonary syndrome (HPS) has gained importance in Latin America
      as an emerging disease, with reports of about 4000 HPS cases; however, this is
      probably an underestimate because of limited surveillance programs and diagnostic
      tools to confirm HPS. In order to address this issue and develop better
      serosurveillance capability, we evaluated three recombinant peptides from the
      Necocli virus (NECV) nucleocapsid in antibody-capture ELISA. We cloned and
      expressed antigens representing the whole NECV nucleocapsid protein (NECV-rN),
      the immunodominant domain (NECV-rN100), and a serospecific domain (NECV-rN428),
      and then we compared these antigens in ELISA to detect IgG antibodies to NECV in
      human sera. We evaluated human sera collected during two epidemiological studies
      from the area where NECV was discovered. The first group included 609 sera from
      healthy individuals, and the second one included 89 samples from patients with
      undifferentiated febrile illness. In these two groups, hantavirus infection had
      previously been determined by the presence of IgG to Maciel virus (MCLV), a
      hantavirus closely related to NECV. The number of IgG-positive sera was higher
      using the Necocli ELISA with the rN100 protein, which detected antibodies in a
      higher percentage of healthy individuals, 129/609 (21.2%), as well as in febrile
      patients, 11/89 (12.3%). In contrast, using MCLV ELISA, 8 of 609 (1.3%) and 4 of
      89 (4.5%) samples from healthy and febrile patients, respectively, were
      seropositive. The agreement between the NECV and MCLV ELISA assays was >= 82.3%;
      however, the kappa indices were weak but statistically significant for rN (0.251
      CI; 0.138-0.365) and rN100rN (0.153 CI; 0.084-0.223). The weak kappa indices were
      attributed to decreased MCLV ELISA assay sensitivity. These results suggest that
      NECV rN and rN100 have increased specificity and could be further validated for
      improved diagnosis of hantavirus infections.

PMID- 30191377
TI  - Rab23 Promotes Hepatocellular Carcinoma Cell Migration Via Rac1/TGF-beta
      Signaling.
AB  - Rab23 is a member of Ras-related small GTPase family, which plays a critical role
      in the progression of wide range of tumors. However, its biological function in
      hepatocellular carcinoma still remains unclear. Here, we investigated the effects
      of Rab23 on proliferation and migration in hepatocellular carcinoma cell and its
      potential mechanisms. We found over-expression of Rab23 promoted the Hep3B
      hepatocellular carcinoma cell migration, which could be reversed by Rab23
      silencing. Rab23 induced Rac1 activation and followed progression of epithelial
      mesenchymal transition (EMT) along with upregulation of N-cadherin, snail as well
      as vimentin and downregulation of E-cadherin via upregulating Transforming Growth
      Factor-beta (TGF-beta). Silencing Rac1 significantly attenuated Rab23-induced
      HepG2 migration and TGF-beta. Moreover, knockdown of TGF-beta effectively
      attenuated Rab23-induced EMT. Taken together, we demonstrated a mechanistic
      cascade of Rab23 enhangcing Rac1 activation and subsequent TGF-beta expression,
      leading to hepatocellular carcinoma cell migration.

PMID- 30191378
TI  - Sensitive Determination of Fentanyl in Low-Volume Serum Samples by LC-MS/MS.
AB  - Fentanyl is a widely used drug in the management of pain. Present LC-MS/MS
      methods for analysis of fentanyl require a large volume of serum, but yet the
      sensitivity was at about 50 pg/mL. Here, we report a modified liquid-liquid
      extraction method for the analysis of fentanyl in serum. The method is very
      sensitive with a LLOQ of 5 pg/mL while using only 0.175 mL of serum for analysis.
      The separation was performed on a Zorbax XDB-C18 column (4.6 * 50 mm, 1.8 MUm,
      600 bar) using a mobile phase of water: acetonitrile (70:30 v/v) with 0.1% formic
      acid that was pumped isocratically at a flow rate of 0.5 mL per minute. The
      calibration curve was found to be linear over a range of 5-10,000 pg/mL. The
      inter-day and intra-day accuracy and precision were tested using low (20 pg/mL),
      medium (1000 pg/mL), and high (5000 pg/mL) quality control samples of fentanyl
      prepared in blank human serum and were within +/- 15% of the nominal value.
      Fentanyl was also found to be stable in various storage and sample preparation
      conditions, including short-term bench-top storage (for 5 h), freeze-thaw cycling
      (three cycles), long-term frozen condition (4.5 months at - 70 degrees C), and
      post-preparative storage (for 48 h).

PMID- 30191379
TI  - Smartly Engineered PEGylated Di-Block Nanopolymeric Micelles: Duo Delivery of
      Isoniazid and Rifampicin Against Mycobacterium tuberculosis.
AB  - In an attempt to deliver multiple drugs through a nanoparticulate platform, the
      present study was designed to deliver isoniazid (INH) and rifampicin (RMP)
      together through conjugation/encapsulation approaches using PEG-PLA (polyethylene
      glycol-poly-L-lactic acid) polymeric micelles. The objective of this study is to
      identify the preparation and evaluation of PEGylated polymeric micelles with dual
      drug delivery of INH and RMP for the effective treatment of tuberculosis (TB).
      Synthesized PEG-PLA di-block-copolymer was further conjugated to INH-forming PEG
      PLA-INH (PPI) conjugate. Separately, these conjugates were loaded with RMP
      building the rifampicin-loaded PEG-PLA-INH polymeric micelles (PMC). The critical
      micelle concentration (CMC) for the PEG-PLA copolymer was found to be 8.9 +/-
      0.96 mg/L, and the size and zeta potential were observed to be 187.9 +/- 2.68 nm
      and - 8.15 +/- 1.24 mV (0.251 +/- 0.042 pdi), respectively. Percent drug loading
      of PMC was 16.66 +/- 1.52 and 23.07 +/- 1.05 with entrapment efficiency of 72.30
      +/- 3.49 and 78.60 +/- 2.67% for RMP and INH, respectively. RBC hemolysis
      capacity of PMC was significantly less than pure RMP and INH. Microplate Alamar
      blue assay (MABA) along with microscopy showed that the nanoconstructed PMC were
      more effective than the drugs, and approximately 8-fold reduction in overall
      minimum inhibitory concentration (MIC) was observed. The prepared duo drug-loaded
      nano-engineered polymeric micelles were highly effective against sensitive
      Mycobacterium tuberculosis strains and found to be less hemolytic in nature. The
      micelles could be further explored (in the future) for in vivo anti-TB studies to
      establish further to achieve better treatment for TB.

PMID- 30191380
TI  - Olfactory Dysfunction in CNS Neuroimmunological Disorders: a Review.
AB  - Olfactory dysfunction is deeply associated with quality of human life in the
      aging population. Olfactory dysfunction is an occasional presymptomatic sign of
      neuroimmunological multiple sclerosis, neuromyelitis optica, and systemic lupus
      erythematosus. Olfaction is initially processed by olfactory receptor cells that
      capture odor molecules, and the signals are transmitted to the glomeruli in the
      olfactory bulbs via olfactory nerves and processed in the primary olfactory
      cortex in the brain. Damage to either the olfactory receptor cells or the
      olfactory bulb and primary olfactory cortex may influence olfactory functioning.
      A close link between neuroimmunological disorders and olfactory dysfunction has
      been reported in patients and animal models. This review summarizes the
      literature data concerning olfactory dysfunction in autoimmune diseases including
      multiple sclerosis, neuromyelitis optica, and systemic lupus erythematosus;
      animal models thereof; and inflammation in the olfactory bulb.

PMID- 30191381
TI  - Ablation of Cytochrome c in Adult Forebrain Neurons Impairs Oxidative
      Phosphorylation Without Detectable Apoptosis.
AB  - Cytochrome c (Cyt c), a heme-containing mitochondrial protein, has a critical
      function in both respiration and apoptosis. Consistent with these vital
      functions, somatic Cyt c mouse knockout is embryonic lethal. In order to
      investigate the sensitivity of postnatal neurons to Cyt c depletion, we developed
      a neuron-specific conditional knockout model. Neuron-specific Cyt c KO mouse
      (nCytcKO) was created by crossing the floxed Cyt c mouse with a CamKIIalpha-cre
      transgenic mouse, which deletes the floxed alleles postnatally. nCytcKO mice were
      normal at birth but developed an abnormal phenotype starting at 8 weeks of age
      with weight loss, tremor, decreased sensorimotor coordination, and sudden death
      between 12 and 16 weeks. Histological analysis did not show major neuronal
      degeneration. Analyses of oxidative phosphorylation showed a specific reduction
      in complex IV levels. Markers of oxidative stress were also increased. This novel
      model showed that neuronal complex IV is destabilized in the absence of Cyt c. It
      also showed that ablation of Cyt c in neurons leads to severe behavioral
      abnormalities and premature death without detectable neuronal loss, suggesting
      that neurons have the potential to survive for extended periods of time without a
      functional OXPHOS.

PMID- 30191382
TI  - Polydatin protects against acute myocardial infarction-induced cardiac damage by
      activation of Nrf2/HO-1 signaling.
AB  - Polydatin is a traditional Chinese medicine that provides myocardial protection
      after acute myocardial infarction (AMI). The study aim was to investigate the
      myocardial protection polydatin in H9c2 myocardial cells cultured in a hypoxic
      atmosphere and in a rat AMI model induced by ligating the left anterior
      descending coronary artery and treated with polydatin 100 mg/kg/day for 30 days.
      The involvement of Nrf2 in mediating the effects of polydatin was investigated in
      H9c2 cells following Nrf2 knockdown by transfection of siRNA. Polydatin
      suppressed hypoxia-induced H9c2 cell apoptosis and reactive oxygen species (ROS)
      generation by promoting Nrf2/HO-1 signaling. Nrf2 knockdown reversed the
      protective effects of polydatin against hypoxia-induced myocardial cell injury.
      The in vivo results were consistent with polydatin suppression of apoptosis and
      ROS generation in myocardial tissue by promotion of Nrf2/HO-1 signaling. In
      conclusion, polydatin effectively inhibited hypoxia- and AMI-induced myocardial
      damage by promotion of Nrf2/HO-1 signaling.

PMID- 30191383
TI  - Executive Dysfunction Early Postnatal Biomarkers among Children Born Extremely
      Preterm.
AB  - We evaluated the relationship between blood levels of inflammatory and
      neurotrophic proteins during the first postnatal month in 692 children born
      before the 28th week of gestation and executive function limitations among those
      10-year olds who had an IQ >= 70. The measures of dysfunction were Z-scores <= -1
      on the Differential Ability Scales-II working memory (WM) assessment) (N = 164),
      the NEPSY-II (A Developmental NEuroPSYchological Assessment-II) Inhibition
      Inhibition assessment) (N = 350), the NEPSY-II Inhibition-Switching assessment)
      (N = 345), as well as a Z-score <= -1 on all three assessments (identified as the
      executive dysfunction composite (N = 104). Increased risks of the executive
      dysfunction composite associated with high concentrations of inflammatory
      proteins (IL-8, TNF-alpha, and ICAM-1) were modulated by high concentrations of
      neurotrophic proteins. This pattern of modulation by neurotrophins of increased
      risk associated with inflammation was also seen for the working memory
      limitation, but only with high concentrations of IL-8 and TNF-alpha, and the
      switching limitation, but only with high concentrations of ICAM-1. We infer that
      among children born extremely preterm, risks of executive function limitations
      might be explained by perinatal systemic inflammation in the absence of adequate
      neurotrophic capability.

PMID- 30191384
TI  - Islet-Like Structures Generated In Vitro from Adult Human Liver Stem Cells Revert
      Hyperglycemia in Diabetic SCID Mice.
AB  - A potential therapeutic strategy for diabetes is the transplantation of induced
      insulin secreting cells. Based on the common embryonic origin of liver and
      pancreas, we studied the potential of adult human liver stem-like cells (HLSC) to
      generate in vitro insulin-producing 3D spheroid structures (HLSC-ILS). HLSC-ILS
      were generated by a one-step protocol based on charge dependent aggregation of
      HLSC induced by protamine. 3D aggregation promoted the spontaneous
      differentiation into cells expressing insulin and several key markers of
      pancreatic beta cells. HLSC-ILS showed endocrine granules similar to those seen
      in human beta cells. In static and dynamic in vitro conditions, such structures
      produced C-peptide after stimulation with high glucose. HLSC-ILS significantly
      reduced hyperglycemia and restored a normo-glycemic profile when implanted in
      streptozotocin-diabetic SCID mice. Diabetic mice expressed human C-peptide and
      very low or undetectable levels of murine C-peptide. Hyperglycemia and a diabetic
      profile were restored after HLSC-ISL explant. The gene expression profile of in
      vitro generated HLSC-ILS showed a differentiation from HLSC profile and an
      endocrine commitment with the enhanced expression of several markers of beta cell
      differentiation. The comparative analysis of gene expression profiles after 2 and
      4 weeks of in vivo implantation showed a further beta-cell differentiation, with
      a genetic profile still immature but closer to that of human islets. In
      conclusion, protamine-induced spheroid aggregation of HLSC triggers a spontaneous
      differentiation to an endocrine phenotype. Although the in vitro differentiated
      HLSC-ILS were immature, they responded to high glucose with insulin secretion and
      in vivo reversed hyperglycemia in diabetic SCID mice.

PMID- 30191385
TI  - Correction to: Probabilistic risk assessment and risk mapping of metals in
      tropical estuarine sediments using the Aquarisk model.
AB  - The original version of this article unfortunately contained a mistake in the
      article title.

PMID- 30191386
TI  - Evaluation of a comprehensive geriatric assessment tool in geriatric cancer
      patients undergoing adjuvant chemotherapy: a pilot study.
AB  - PURPOSE: It is recommended to use comprehensive geriatric assessment (CGA) in
      clinical oncology practice to improve care for geriatric cancer patients and to
      identify medical and social issues that may need further intervention. The
      purpose of this pragmatic pilot study was to evaluate the effectiveness of the
      Hurria et al. CGA in cancer patients 70 years of age or older undergoing adjuvant
      chemotherapy, as well as the feasibility of integrating it into a busy clinic
      practice and the psychosocial impact on these patients. METHOD: Twenty-five
      patients were recruited. Descriptive analysis was performed via a geriatric
      assessment questionnaire completed by the participants prior to their first
      adjuvant chemotherapy treatment and during follow-up, 2 to 6 weeks after last
      treatment. Additionally, study staff performed a geriatric healthcare assessment
      at both time points. RESULTS: The results of this pilot study show that
      administration is feasible despite some challenges. Administration of a CGA in a
      clinic setting presented some logistical issues with regard to time and space
      available in clinic. Analysis of patient data indicated only minor variations in
      patient domains from pre-chemo to post-chemo confirming previous research.
      Participants expressed gratitude for the extra time spent with them at a
      stressful time in their lives. CONCLUSION: Further information regarding the
      usefulness of a comprehensive geriatric assessment with regard to improving
      treatment selection, identifying undetected medical problems, and avoiding
      toxicity will be obtained if the administration of comprehensive geriatric
      questionnaires is incorporated into the clinic setting and considered into the
      allocated time for staff workload.

PMID- 30191387
TI  - Patients and caregivers' unmet information needs in the field of patient
      education: results from an Italian multicenter exploratory survey.
AB  - Patient education and empowerment (PEE) is aimed at improving competence of
      patients during their clinical path and enabling healthcare providers with
      specific communication strategies. We investigated the interest of Italian Cancer
      Research & Care Centers (CRCI) users (patients and caregivers) in being involved
      in PEE activities. An anonymous questionnaire addressed to users was distributed
      between June 2013 and February 2014. The questionnaire gathered information on
      the following: health-related topics; 13 different PEE initiatives/modalities of
      learning already active at CRCI; personal demographic data; the willingness to be
      more involved in the organization of health services provided and in which
      context; and five preferred info-educational activities. Frequency distribution
      and chi-square analysis were computed. Statistical significance (p value) was set
      at < 0.05. A total of 875 (29%) users responded to the 3000 distributed
      questionnaires. The first three priorities of interest were "early diagnosis"
      (18%), "prevention" (17%), and "diagnosis explanation" (13%). The first three
      priorities on informational activity were as follows: "classes on cancer-related
      topics with healthcare professionals" (28%); "cancer information service" (22%);
      "drug information point" (7%). Forty-nine percent of the respondents stated that
      they would like to be involved in the organization of PEE activities,
      particularly caregivers and users older than 55 years of age. The preferred
      educational activities were "classes on cancer-related topics with healthcare
      professionals" and "cancer information service" on a face-to-face modality.
      Patients were more interested than caregivers in "prevention." The extension of
      PEE programs to all CRCI users into routine care will be the next step of the
      present research.

PMID- 30191388
TI  - [Change in rheumatic hip surgery].
AB  - There is a trend towards a reduction in joint-preserving hip surgery, such as
      synovectomy and total hip joint replacement in rheumatic patients. This is mostly
      due to the success of biological disease-modifying antirheumatic drugs (bDMARD)
      in systemic anti-rheumatic therapy. The results of hip surgery in rheumatic
      patients are comparable to those in non-rheumatic patients, except for prosthetic
      joint infections, which are higher in patients with rheumatoid arthritis.
      Especially in hip surgery there was a big evolution in the last few years
      including a broad range of minimally invasive surgical methods, such as hip
      arthroscopy, mini-open hip surgery and minimally invasive hip arthroplasty with
      bone preservation or short femoral shafts. These surgical methods also have an
      advantage in the treatment of typical rheumatoid pathologies and have the benefit
      of a rapid recovery.

PMID- 30191389
TI  - [Rheumatoid arthritis-mimics : When appearances are deceptive].
AB  - Rheumatology represents a discipline full of differential diagnoses. Even for
      classical diseases, such as rheumatoid arthritis as the most frequent chronic
      inflammatory joint disease and described so clearly in many textbooks, it is not
      uncommon that it can be a diagnostic challenge in daily practice. This applies to
      arthritic joint involvement and also to frequently associated extra-articular
      manifestations. The patient history and results of the clinical examination are
      essential; however, laboratory and imaging findings often make a significant
      contribution to confirming the diagnosis, especially in early phases of the
      disease. This article, which makes no claims to completeness, focuses on diseases
      that in the opinion of the authors can imitate rheumatoid arthritis due to
      similar joint and other organ manifestations. These include metabolic,
      inflammatory infective and non-infective as well as tumorous diseases. A
      misinterpretation as rheumatoid arthritis as a rule leads to long-term and severe
      consequences for affected patients. Thus, the diagnosis of rheumatoid arthritis
      should be questioned and re-evaluated in cases of unusual accompanying symptoms,
      atypical course of disease and a lack of response to standard treatment
      approaches.

PMID- 30191390
TI  - Comparison of the efficacy and safety of tofacitinib and baricitinib in patients
      with active rheumatoid arthritis: a Bayesian network meta-analysis of randomized
      controlled trials.
AB  - OBJECTIVES: The relative efficacy and safety of tofacitinib and baricitinib were
      assessed in patients with rheumatoid arthritis (RA) with an inadequate response
      to disease-modifying anti-rheumatic drugs (DMARDs) or biologics. METHODS: We
      performed a Bayesian network meta-analysis to combine direct and indirect
      evidence from randomized controlled trials (RCTs) to examine the efficacy and
      safety of tofacitinib and baricitinib in combination with DMARDs in RA patients
      with an inadequate DMARD or biologic response. RESULTS: Twelve RCTs including
      5883 patients met the inclusion criteria. There were 15 pairwise comparisons
      including 10 direct comparisons of 6 interventions. Tofacitinib 10 mg +
      methotrexate (MTX) and baricitinib 4 mg + MTX were among the most effective
      treatments for active RA with an inadequate DMARD or biologic response, followed
      by baricitinib 2 mg + MTX, tofacitinib 5 mg + MTX, and adalimumab + MTX. The
      ranking probability based on the surface under the cumulative ranking curve
      (SUCRA) indicated that tofacitinib 10 mg + MTX had the highest probability of
      being the best treatment to achieve the ACR20 response rate (SUCRA = 0.865),
      followed by baricitinib 4 mg + MTX (SUCRA = 0.774), baricitinib 2 mg + MTX (SUCRA
      = 0.552), tofacitinib 5 mg + MTX (SUCRA = 0.512), adalimumab + MTX (SUCRA =
      0.297), and placebo + MTX (SUCRA <0.001). No significant differences were
      observed in the incidence of serious adverse events after treatment with
      tofacitinib + MTX, baricitinib + MTX, adalimumab + MTX, or placebo + MTX.
      CONCLUSIONS: In RA patients with an inadequate response to DMARDs or biologics,
      tofacitinib 10 mg + MTX and baricitinib 4 mg + MTX were the most efficacious
      interventions and were not associated with a significant risk of serious adverse
      events.

PMID- 30191391
TI  - [Adolescent rheumatism : The same but different].
AB  - Between childhood and adulthood, there often exists a difficult period of coming
      of age. This phase frequently represents a significant challenge for adolescents
      and young adults at the physical, psychological, and social level. Having trouble
      with adolescence itself it puts an extra weight on young people with chronic
      rheumatic diseases. Thus, medical and interpersonal support can be multifaceted.
      In light of this, support from an interprofessional team in the form of a
      specialist transition clinic has proven to be of great value. In the outpatient
      clinic established at the Inselspital Bern (Bern University Hospital),
      specialists in pediatric and adult rheumatology work together with a team of
      nurses, physiotherapists, occupational therapists, social workers, and
      psychologists, who are called in on an individual-requirement basis. All
      personnel involved in the care of these young patients should understand that a
      rheumatic disease developing in childhood normally progresses differently than it
      does if first developed during adulthood.

PMID- 30191392
TI  - First case of pleural amyloidosis in systemic erythematosus: report and
      literature review.

PMID- 30191394
TI  - Analysis of a practical surgical skills laboratory for nerve sparing radical
      prostatectomy.
AB  - PURPOSE: With the rapidly expanding anatomical and technical knowledge
      surrounding nervesparing radical prostatectomy (NSRP), anatomical and operative
      textbooks have failed to keep pace with the literature. A surgical skill
      laboratory (SSL) was designed to educate urology trainees on surgical anatomy and
      techniques for NSRP. The objective was to assess the validity of a SSL program.
      METHODS: A low-fidelity, anatomically accurate prostate model with its
      appropriate fascial coverings and location of the neurovascular bundle was
      created. Participants were surveyed prior to a SSL workshop for their knowledge
      of NSRP focusing on clinical and anatomical considerations. An interactive 2-h
      tutorial and workshop was then undertaken outlining the clinical and anatomical
      nuances for NSRP, with participants then practising an intra and inter-fascial
      NSRP on the model. Participants were resurveyed immediately after the workshop
      and at 6 months. RESULTS: Thirty participants completed the NSRP workshop.
      Significant differences (p < 0.0001) in anatomical and clinical knowledge were
      noted after the workshop with improvements for both junior and senior trainees.
      The knowledge was retained at 6 months following the workshop. CONCLUSIONS: A low
      fidelity bench-top model is a feasible and reproducible technique for improving
      the understanding of periprostatic anatomy and the different surgical approaches
      for NSRP. The SSL is useful and knowledge gained appears to be retained by
      workshop participants. SSL workshops are a valid hands-on approach to teaching
      surgical skills and should remain an integral part of urology training.

PMID- 30191393
TI  - Efficacy of intra-arterial chemotherapy combined with intravesical chemotherapy
      in T1G3 bladder cancer when compared with intravesical chemotherapy alone after
      bladder-sparing surgery: a retrospective study.
AB  - PURPOSE: To assess the efficacy of intra-arterial chemotherapy (IAC) combined
      with intravesical chemotherapy (IVC) in T1G3 bladder cancer (Bca) after
      transurethral resection of bladder tumor (TURBT). METHODS: Our study
      retrospectively reviewed 200 patients with T1G3 BCa who had all undergone TURBT.
      The patients' medical records were divided into two groups, one group only had
      IVC with pirarubicin after surgery, and the other group had IAC (cisplatin and
      epirubicin) combined with IVC after surgery. The patients were monitored
      regularly by urine cytology and cystoscopy. Survival and recurrence curves were
      calculated using the Kaplan-Meier method. Tumor recurrence, progression and tumor
      specific death rate were compared with Chi-square test. A multivariate analysis
      was carried out to find out potential confounders. RESULTS: A total of 200
      medical record was analyzed, 131 patients received IVC, 69 IAC + IVC treatment,
      tumor-specific death rate between the combined IAC and IVC compared to IVC alone
      was 7.25 and 17.6%, respectively (p < 0.05); the tumor recurrence rate between
      the two groups was 31.8% (22/69) and 44.3%, respectively (58/131) (p < 0.05), and
      tumor recurred later in the IAC + IVC group (p < 0.05), tumor progression rate
      was 18.8% (13/69) and 28.2% (37/131), respectively, with p < 0.05. Overall
      survival was longer in IAC + IVC group (p < 0.05). Using the multivariable
      regression model, IAC was significantly related to disease recurrence (p < 0.05)
      and overall survival (p < 0.05). CONCLUSION: T1G3 BCa post-TURBT surgery patients
      who underwent IAC combined with IVC had a longer overall survival and increased
      time interval to first recurrence, lower tumor recurrence rate, progression rate
      and tumor-specific death rate than compared with those who only underwent IVC
      alone.

PMID- 30191395
TI  - A new checklist method enhances treatment compliance and response of behavioural
      therapy for primary monosymptomatic nocturnal enuresis: a prospective randomised
      controlled trial.
AB  - PURPOSE: The aim of the study was to demonstrate the benefits of a newly
      established written checklist of behavioural instructions for monosymptomatic
      nocturnal enuresis. METHODS: From a total of 96 parents with children who
      complain of bedwetting three or more nights per week for at least 14 days, 79
      were randomly divided into three groups. Group I (n = 27) were instructed to
      apply only behavioural therapy as a written guideline, Group II (n = 26) were
      instructed to apply behavioural therapy with a written checklist for parents to
      fully complete and Group III (n = 26) received desmopressin treatment plus verbal
      behavioural therapy. All participants were analysed in respect of compliance and
      the response rate to treatment over a time period of 8 weeks. RESULTS: A total of
      63 participants completed the study period. The participants in all three groups
      were similar in terms of the age of the child and the parents, number of
      siblings, and the educational and economic status of the parents (p > 0.05). High
      rates of treatment compliance were determined for the participants with the
      checklist compared to those with written guideline. No statistically significant
      difference was determined between Group II and III in respect of compliance rates
      (p = 0.12). The treatment response rates of the participants in Group I were
      significantly lower compared to those of Group II and III (p = 0.001) with no
      statistical difference determined between Groups II and III (p = 0.15).
      CONCLUSION: The success rate of behavioural therapy for MNE can be increased with
      the newly-designed method of a written checklist form of behavioural
      instructions.

PMID- 30191397
TI  - Chemotherapy and targeted therapy for breast cancer patients with hepatitis C
      virus infection.
AB  - BACKGROUND: Hepatitis C virus infection (HCV) is a major health problem in Egypt.
      Breast cancer is the most common cancer among Egyptian women. Considering that
      both diseases are frequent in the Egyptian population, it is likely that many
      women are affected by both. PURPOSE: To evaluate patient safety and applicability
      of chemotherapy in chronic hepatitis C virus-infected patients with breast
      cancer. SUBJECTS AND METHODS: We performed retrospective survey of 58 Egyptian
      patients diagnosed with both diseases. We retrospectively investigated the
      baseline patient and tumor characteristics, the toxicities of chemotherapy, and
      the changes in HCV viral load before and after chemotherapy, in addition to
      treatment received for HCV infection. RESULTS: Forty-four (75.9%) out of the 58
      patients received chemotherapy with or without trastuzumab and one patient
      received lapatinib. We reported 2 patients who had HCV viral reactivation.
      Treatment with trastuzumab or Lapatinib was not associated with elevation in
      liver enzymes or change in HCV RNA viral load. Treatment discontinuation occurred
      in 31.8% (14/44) of patients due to complications. Dose reductions and/or dose
      delays were common (27.2%). Elevated liver enzymes were developed in 20 out of 44
      (45.5%) patients who received chemotherapy. Three patients received antiviral
      treatment concomitant with chemotherapy with no significant complications.
      CONCLUSIONS: Greater attention should be paid to the possibility of complications
      including HCV reactivation, fulminant hepatitis, and interrupted chemotherapy
      treatments in breast cancer patients with chronic HCV infection receiving
      immunosuppressive drugs. Close monitoring of patients with breast cancer and HCV
      infection should be done.

PMID- 30191396
TI  - Stereotactic ablative radiation therapy for oligometastatic prostate cancer
      delays time-to-next systemic treatment.
AB  - PURPOSE: Local ablative treatment to oligometastatic patients can result in long
      term disease-free survival in some cancer patients. The importance of this
      treatment paradigm in prostate cancer is a rapidly evolving field. Herein, we
      report on the safety and preliminary clinical outcomes of a modern cohort of
      oligometastatic prostate cancer (OPC) patients treated with consolidative
      stereotactic ablative radiation (SABR). METHODS: Records of men with OPC who
      underwent consolidative SABR at our institution were reviewed. SABR was delivered
      in 1-5 fractions of 5-18 Gray. Kaplan-Meier estimates of local progression-free
      survival (LPFS), biochemical progression-free survival (bPFS; PSA nadir + 2),
      distant progression-free survival (DPFS), and time-to-next intervention (TTNI)
      were calculated. RESULTS: In total, 66 OPC patients were identified with
      consolidative SABR delivered to 134 metastases: 89 bone, 40 nodal, and 5 viscera.
      The majority of men (49/66) had hormone-sensitive prostate cancer (HSPC). Crude
      grade 1 and 2 acute toxicities were 36% and 11%, respectively, with no >= grade 3
      toxicity. At 1 year, LPFS was 92% and bPFS and DPFS were 69%. Of the 18 men with
      HSPC who had deferred hormone therapy , 11 (56%) remain disease free following
      SABR (1-year ADT-FS was 78%). In 17 castration-resistant men, 11 had > 50%
      prostate-specific antigen (PSA) declines with 1-year TTNI of 30%. CONCLUSIONS:
      Consolidative SABR in OPC is feasible and well tolerated. The heterogeneity and
      small size of our series limit extrapolation of clinically meaningful outcomes
      following consolidative SABR in OPC, but our preliminary data suggest that this
      approach warrants continued prospective study.

PMID- 30191399
TI  - Assessment of Human Health Risk of Toxic Elements Due to Cinnamon Ingestion in
      the Diet.
AB  - Recent studies highlighted the beneficial action of cinnamon on postprandial
      glycemia and LDL-cholesterol concentrations, both in healthy subjects and type 2
      diabetic patients. Inclusion of 3 to 6 g of cinnamon in diet revealed a
      beneficial effect on glucose metabolism control in non-diabetic adults during
      postprandial period. Given the levels of toxic elements present in cinnamon
      species from different countries, such large daily intakes of cinnamon can easily
      exceed their maximum permissible limits and, consequently, induce adverse health
      effects. This study aimed to investigate the elemental concentration profile in
      cinnamon powder products available in the Portuguese market and to assess the
      cumulative non-carcinogenic risk to human health due to the exposure to mixtures
      of such elements through the inclusion of 6 g of cinnamon in diet. Concentrations
      of Cu, Zn, Fe, Al, Cl, Mn, and Sr were determined by wavelength dispersive X-ray
      fluorescence spectroscopy in different lots of eight branded and one bulk
      cinnamon powder products. Linear mixed models have revealed significant
      differences in concentrations of Zn, Fe, Al, and Cl between brands. In
      particular, bulk cinnamon samples presented the highest contents of Fe (475.0
      490.0 mg kg-1) and Al (1139.0-1336.0 mg kg-1). The non-carcinogenic risk was
      assessed following EPA's guidelines through the hazard quotient (HQ). Estimated
      HQ values were lower than the USEPA guideline of 1. Additionally, the hazard
      index (HI), representing the combined non-carcinogenic effects of all toxic
      elements, revealed no potential human health risk for heavy consumers of cinnamon
      (HI = 0.660). AbstractGraphical ?.

PMID- 30191398
TI  - Comprehensive network map of interferon gamma signaling.
AB  - Interferon gamma (IFN-gamma), is a cytokine, which is an important regulator of
      host defense system by mediating both innate and adaptive immune responses. IFN
      gamma signaling is primarily associated with inflammation and cell-mediated
      immune responses. IFN-gamma is also represented as antitumor cytokine which
      facilitates immunosurveillance in tumor cells. In addition, IFN-gamma mediated
      signaling also elicits pro-tumorigenic transformations and promotes tumor
      progression. Impact of IFN-gamma signaling in mammalian cells has been widely
      studied which indicate that IFN-gamma orchestrates distinct cellular functions
      including immunomodulation, leukocyte trafficking, apoptosis, anti-microbial, and
      both anti- and pro-tumorigenic role. However, a detailed network of IFN-gamma
      signaling pathway is currently lacking. Therefore, we systematically curated the
      literature information pertaining to IFN-gamma signaling and develop a
      comprehensive signaling network to facilitate better understanding of IFN-gamma
      mediated signaling. A total of 124 proteins were catalogued that were
      experimentally proven to be involved in IFN-gamma signaling cascade. These 124
      proteins were found to participate in 81 protein-protein interactions, 94 post
      translational modifications, 20 translocation events, 54 activation/inhibiton
      reactions. Further, 236 differential expressed genes were also documented in IFN
      gamma mediated signaling. IFN-gamma signaling pathway is made freely available to
      scientific audience through NetPath at (
      http://www.netpath.org/pathways?path_id=NetPath_32 ). We believe that
      documentation of reactions pertaining to IFN-gamma signaling and development of
      pathway map will facilitate further research in IFN-gamma associated human
      diseases including cancer.

PMID- 30191400
TI  - Molecular Targets of the Hydrophobic Block of Pluronics in Cells: a Photo
      Affinity Labelling Approach.
AB  - PURPOSE: Pluronics are known as inhibitors of multidrug resistance thus making
      tumor cells sensitive to therapeutic doses of drugs. The purpose of our study
      consists in revealing molecular targets of the hydrophobic poly(propylene oxide)
      block of pluronics in living cells and the dependence of the polymers
      chemosensitizing efficiency upon targeting. METHODS: A photo sensitive tracer was
      attached to the hydrophobic poly(propylene oxide) block of 3H-labeled tert-Bu-EO
      PO copolymer. The conjugate was used for treatment cells in culture. We searched
      for its complexes with cellular lipids or proteins using RP TLC and SDS
      electrophoresis, respectively. The chemosensitizing efficiency of pluronics was
      evaluated by their least concentrations sufficient for MDR reversion (CMDR).
      RESULTS: The poly(propylene oxide) block inserts in the lipid core of plasma
      membrane. No preferential binding of the conjugate with any cellular protein,
      particularly P-gp, has been detected. FITC-labeled pluronic L61 bound to alcohol
      insoluble cellular targets did not participate in MDR reversion. CMDR values of
      13 block copolymers have been determined. These values inversely correlated with
      the polymers affinity toward lipids and the ability to accelerate flip-flop.
      CONCLUSION: Insertion of the hydrophobic poly(propylene oxide) block of
      amphiphiles in the lipid core of plasma membrane and acceleration of flip-flop of
      lipids underlie the mechanism of MDR reversion.

PMID- 30191401
TI  - Region-specific depletion of synaptic mitochondria in the brains of patients with
      Alzheimer's disease.
AB  - Of all of the neuropathological changes observed in Alzheimer's disease (AD), the
      loss of synapses correlates most strongly with cognitive decline. The precise
      mechanisms of synapse degeneration in AD remain unclear, although strong evidence
      indicates that pathological forms of both amyloid beta and tau contribute to
      synaptic dysfunction and loss. Synaptic mitochondria play a potentially important
      role in synapse degeneration in AD. Many studies in model systems indicate that
      amyloid beta and tau both impair mitochondrial function and impair transport of
      mitochondria to synapses. To date, much less is known about whether synaptic
      mitochondria are affected in human AD brain. Here, we used transmission electron
      microscopy to examine synapses and synaptic mitochondria in two cortical regions
      (BA41/42 and BA46) from eight AD and nine control cases. In this study, we
      observed 3000 synapses and find region-specific differences in synaptic
      mitochondria in AD cases compared to controls. In BA41/42, we observe a fourfold
      reduction in the proportion of presynaptic terminals that contain multiple
      mitochondria profiles in AD. We also observe ultrastructural changes including
      abnormal mitochondrial morphology, the presence of multivesicular bodies in
      synapses, and reduced synapse apposition length near plaques in AD. Together, our
      data show region-specific changes in synaptic mitochondria in AD and support the
      idea that the transport of mitochondria to presynaptic terminals or synaptic
      mitochondrial dynamics may be altered in AD.

PMID- 30191403
TI  - Ants Do Not Traverse the Silk of Adult Female Nephila clavipes (Linnaeus) Webs.
AB  - Many organisms use chemicals to deter enemies. Some spiders can modify the
      composition of their silk to deter predators from climbing onto their webs. The
      Malaysian golden orb-weaver Nephila antipodiana (Walckenaer) produces silk
      containing an alkaloid (2-pyrrolidinone) that functions as a defense against ant
      invasion-ants avoid silk containing this chemical. In the present study, we test
      the generality of ants' silk avoidance behavior in the field. We introduced three
      ant species to the orb webs of Nephila clavipes (Linnaeus) in the tropical
      rainforest of La Selva, Costa Rica. We found that predatory army ants (Eciton
      burchellii Westwood) as well as non-predatory leaf-cutting ants (Atta cephalotes
      Linnaeus and Acromyrmex volcanus Wheeler) avoided adult N. clavipes silk,
      suggesting that an additional species within genus Nephila may possess ant
      deterring silk. Our field assay also suggests that silk avoidance behavior is
      found in multiple ant species.

PMID- 30191402
TI  - Opposite development of short- and long-range anterior cingulate pathways in
      autism.
AB  - Autism has been linked with the changes in brain connectivity that disrupt neural
      communication, especially involving frontal networks. Pathological changes in
      white matter are evident in adults with autism, particularly affecting axons
      below the anterior cingulate cortices (ACC). It is still unknown whether axon
      pathology appears early or late in development and whether it changes or not from
      childhood through adulthood. To address these questions, we examined typical and
      pathological development of about 1 million axons in post-mortem brains of
      children, adolescents, and adults with and without autism (ages 3-67 years). We
      used high-resolution microscopy to systematically sample and study quantitatively
      the fine structure of myelinated axons in the white matter below ACC. We provide
      novel evidence of changes in the density, size and trajectories of ACC axons in
      typical postnatal development from childhood through adulthood. Against the
      normal profile of axon development, our data revealed lower density of myelinated
      axons that connect ACC with neighboring cortices in children with autism. In the
      course of development the proportion of thin axons, which form short-range
      pathways, increased significantly in individuals with autism, but remained flat
      in controls. In contrast, the relative proportion of thick axons, which form long
      range pathways, increased from childhood to adulthood in the control group, but
      decreased in autism. Our findings provide a timeline for profound changes in axon
      density and thickness below ACC that affect axon physiology in a direction
      suggesting bias in short over distant neural communication in autism.
      Importantly, measures of axon density, myelination, and orientation provide white
      matter anisotropy/diffusivity estimates at the level of single axons. The
      structural template established can be used to compare with measures obtained
      from imaging in living subjects, and guide analysis of functional and structural
      imaging data from humans for comparison with pathological states.

PMID- 30191404
TI  - Genetic Aspects of Keratoconus: A Literature Review Exploring Potential Genetic
      Contributions and Possible Genetic Relationships with Comorbidities.
AB  - INTRODUCTION: Keratoconus (KC) is a complex, genetically heterogeneous,
      multifactorial degenerative disorder that is accompanied by corneal ectasia which
      usually progresses asymmetrically. With an incidence of approximately 1 per 2000
      and 2 cases per 100,000 population presenting annually, KC follows an autosomal
      recessive or dominant pattern of inheritance and is, apparently, associated with
      genes that interact with environmental, genetic, and/or other factors. This is an
      important consideration in refractive surgery in the case of familial KC, given
      the association of KC with other genetic disorders and the imbalance between
      dizygotic twins. The present review attempts to identify the genetic loci
      contributing to the different KC clinical presentations and relate them to the
      common genetically determined comorbidities associated with KC. METHODS: The
      PubMed, MEDLINE, Google Scholar, and GeneCards databases were screened for KC
      related articles published in English between January 2006 and November 2017.
      Keyword combinations of "keratoconus," "risk factor(s)," "genetics," "genes,"
      "genetic association(s)," and "cornea" were used. In total, 217 articles were
      retrieved and analyzed, with greater weight placed on the more recent literature.
      Further bibliographic research based on the 217 articles revealed another 124
      relevant articles that were included in this review. Using the reviewed
      literature, an attempt was made to correlate genes and genetic risk factors with
      KC characteristics and genetically related comorbidities associated with KC based
      on genome-wide association studies, family-based linkage analysis, and candidate
      gene approaches. RESULTS: An association matrix between known KC-related genes
      and KC symptoms and/or clinical signs together with an association matrix between
      identified KC genes and genetically related KC comorbidities/syndromes were
      constructed. CONCLUSION: Twenty-four genes were identified as potential
      contributors to KC and 49 KC-related comorbidities/syndromes were found. More
      than 85% of the known KC-related genes are involved in glaucoma, Down syndrome,
      connective tissue disorders, endothelial dystrophy, posterior polymorphous
      corneal dystrophy, and cataract.

PMID- 30191405
TI  - [Urinary incontinence after radical prostatectomy : Possibilities of conservative
      management].

PMID- 30191406
TI  - Authors' Response to Comments on "A Retrospective Cross-Sectional Review of
      Resident Care-Seeking at a Physician Health Program".

PMID- 30191407
TI  - Visual attentional load affects the frequency of involuntary autobiographical
      memories and their level of meta-awareness.
AB  - Involuntary autobiographical memories (IAMs) are memories of past events that
      come to mind without deliberate retrieval attempts. Common in everyday life, IAMs
      have recently become a topic of experimental investigations with laboratory
      procedures. In the present study, we build on the recent methodological
      advancements in the study of IAMs, and we investigate the effects of manipulating
      the attentional load on the incidence of IAMs, as well as on the level of meta
      awareness of these memories. In two experiments, attentional load was manipulated
      by varying the demands of the focal vigilance task, and reports of IAMs were
      collected. In Experiment 1, participants were instructed to stop the vigilance
      task whenever mental contents unrelated to the task came to their minds (self
      caught method). In Experiment 2, participants were intermittently interrupted and
      probed regarding the contents of their experience (probe-caught method) and the
      level of meta-awareness for these contents. In both experiments, we found a
      reduction in the frequency of reported IAMs under increased attentional load.
      Moreover, in Experiment 2, IAMs were characterized by varied levels of meta
      awareness, which was reduced by increased attentional load. These results
      indicate that allocation of attentional resources toward a focal task reduces
      reporting of IAMs experienced while performing this task because attentional
      resources play a role in both retrieval of IAMs and the realization that one is
      experiencing a memory.

PMID- 30191408
TI  - The first, the least and the last: Spatial asymmetries in memory and their
      relation to script trajectory.
AB  - Serial positioning biases are well documented and generally take a U-shaped form,
      with better memory for first (primacy) and last items (recency). Here, we test
      the hypothesis that the relative strength of primacy and recency depends on
      script direction. When presented with large arrays of images, people are expected
      to first direct attention to the side where they usually start reading (in our
      case, left among Italian, and right among Arabic speakers) and to then scan the
      remaining images along the habitual text trajectory. Besides supporting the
      predicted scanning direction with an eye-tracker methodology, Study 1a (n = 56
      Italians) provides evidence for a spatial memory advantage for images positioned
      to the left. Study 1b (n = 34 Italians) shows that people are aware of the
      asymmetric scanning and the memory advantage deriving from it. Study 3 (n = 67
      Italian and n = 44 Arabic speakers) shows opposite memory biases in the two
      samples, with best performance for images on the left among Italian and for
      images on the right among Arabic speakers. Together these studies contribute to
      the growing literature showing that scanning habits due to script direction exert
      a subtle influence on basic cognitive processes.

PMID- 30191409
TI  - A close call: Interference from semantic neighbourhood density and similarity in
      language production.
AB  - The present study investigated how lexical selection is influenced by the number
      of semantically related representations (semantic neighbourhood density) and
      their similarity (semantic distance) to the target in a speeded picture-naming
      task. Semantic neighbourhood density and similarity as continuous variables were
      used to assess lexical selection for which competitive and noncompetitive
      mechanisms have been proposed. Previous studies found mixed effects of semantic
      neighbourhood variables, leaving this issue unresolved. Here, we demonstrate
      interference of semantic neighbourhood similarity with less accurate naming
      responses and a higher likelihood of producing semantic errors and omissions over
      accurate responses for words with semantically more similar (closer) neighbours.
      No main effect of semantic neighbourhood density and no interaction between
      semantic neighbourhood density and similarity was found. We assessed further
      whether semantic neighbourhood density can affect naming performance if semantic
      neighbours exceed a certain degree of semantic similarity. Semantic similarity
      between the target and each neighbour was used to split semantic neighbourhood
      density into two different density variables: The number of semantically close
      neighbours versus distant neighbours. The results showed a significant effect of
      close, but not of distant, semantic neighbourhood density: Naming pictures of
      targets with more close semantic neighbours led to longer naming latencies, less
      accurate responses, and a higher likelihood for the production of semantic errors
      and omissions over accurate responses. The results show that word inherent
      semantic attributes such as semantic neighbourhood similarity and the number of
      coactivated close semantic neighbours modulate lexical selection supporting
      theories of competitive lexical processing.

PMID- 30191410
TI  - Growth Behavior and Fatty Acid Production of Probiotics, Pediococcus acidilactici
      and Lactococcus lactis, at Different Concentrations of Fructooligosaccharide:
      Studies Validating Clinical Efficacy of Selected Synbiotics on Growth Performance
      of Caspian Roach (Rutilus frisii kutum) Fry.
AB  - Growth behavior and production of short-chain fatty acid (SCFA) of two
      probiotics, Pediococcus acidilactici and Lactococcus lactis, each at 107 cfu/g
      (P1, L1) and 1010 cfu/g (P2, L2) at different concentrations of
      fructooligosaccharide (FOS) [0.5% (F1), 1% (F2), and 2% (F3)] were assessed in
      vitro. The time to reach the maximum growth of the probiotics in all 12
      treatments was between 8 to 10 h, with the highest and the lowest growth rates
      obtained in F1L1P1 (0.34 +/- 0.02 OD) and F3L1P1 (0.31 +/- 0.05 OD) treatments,
      respectively. The shortest and the longest generation times were seen in F1L1P1
      (112 +/- 1.5 min) and F2L1P1 (231 +/- 0.5 min) treatments, respectively. The
      highest and the lowest levels of SCFA production were found in F1L1P1 (17.94 +/-
      0.74 mg/L) and F3L1P1 (12.98 +/- 0.85 mg/L) treatments, respectively. The three
      synbiotics with the highest SCFA production were then fed to Caspian roach
      (Rutilus frisii kutum) fry weighing 0.75 +/- 0.02 g at 28  degrees C for 60 days,
      to assess growth performance and enzymatic activity. The best growth performance
      in terms of weight gain (WG), protein efficiency ratio (PER), net protein
      utilization (NPU), and food conversion ratio (FCR) were seen with F1L1P1. In
      addition, the highest activity levels of the digestive enzymes chymotrypsin,
      lipase, and amylase were obtained with F1P1L1. The correlation of these in vitro
      and in vivo data demonstrated that oral application of these two probiotics each
      at 107 cfu/g feed plus 0.5% FOS can improve growth and gut enzyme activity of
      Caspian roach fry.

PMID- 30191411
TI  - Ivabradine preserves dynamic sympathetic control of heart rate despite inducing
      significant bradycardia in rats.
AB  - Ivabradine is a selective bradycardic agent that inhibits hyperpolarization
      activated cyclic nucleotide-gated (HCN) channels. HCN channels play a key role in
      mediating the positive chronotropic response to sympathetic nerve stimulation
      (SNS). We examined whether ivabradine would interfere with dynamic sympathetic
      control of heart rate (HR). The effect of intravenous ivabradine (2 mg/kg, n = 7)
      or metoprolol (10 mg/kg, n = 6) on the transfer function from SNS to HR was
      examined in anesthetized rats. Ivabradine preserved the asymptotic dynamic gain
      of the HR transfer function and nearly doubled the asymptotic dynamic gain of the
      transfer function from SNS to the R-R interval. In contrast, metoprolol abolished
      dynamic sympathetic control of HR. Preserved dynamic sympathetic control of HR,
      with coexisting bradycardia, may contribute to some of the beneficial effects of
      ivabradine previously reported in clinical application.

PMID- 30191412
TI  - Blood pressure-independent increase in the cortical cerebral blood flow induced
      by manual acupuncture of the auricular region in rats.
AB  - We aimed to determine whether acupuncture to the auricular region increases
      cortical regional cerebral blood flow (rCBF). The rCBF was measured using laser
      speckle contrast imaging in urethane-anesthetized rats. Acupuncture stimulation
      was performed manually at the auricular concha or abdomen. The former's
      stimulation significantly increased the rCBF of the bilateral cerebral cortex in
      the frontal, parietal, and occipital lobes without altering the systemic arterial
      pressure. In contrast, abdominal stimulation affected neither rCBF nor systemic
      arterial pressure. The increase in the rCBF was completely abolished by the
      severance of the somatic nerves that innervated the auricular region, comprising
      the trigeminal nerve, facial nerve, auricular branch of the vagal nerve,
      glossopharyngeal nerve, and great auricular nerve. Thus, application of
      acupuncture to the auricular region increases the rCBF without increasing
      arterial pressure.

PMID- 30191413
TI  - Ultrasound and color Doppler applications in chronic kidney disease.
AB  - Chronic kidney disease (CKD) includes all clinical features and complications
      during the progression of various kidney conditions towards end-stage renal
      disease (ESRD). These conditions include immune and inflammatory disease such as:
      primary and hepatitis C virus (HCV)-related glomerulonephritis; infectious
      disease such as pyelonephritis with or without reflux and tuberculosis; vascular
      disease such as chronic ischemic nephropathy; hereditary and congenital disease
      such as polycystic disease and congenital cystic dysplasia; metabolic disease
      including diabetes and hyperuricemia; and systemic disease (collagen disease,
      vasculitis, myeloma). During the progression of CKD, ultrasound imaging and color
      Doppler imaging (US-CDI) can differentiate the etiology of the renal damage in
      only 50-70% of cases. Indeed, the end-stage kidney appears shrunken, reduced in
      volume (O < 9 cm), unstructured, amorphous, and with acquired cystic degeneration
      (small and multiple cysts involving the cortex and medulla) or nephrocalcinosis,
      but there are rare exceptions, such as polycystic kidney disease, diabetic
      nephropathy, and secondary inflammatory nephropathies. The main difficulties in
      the differential diagnosis are encountered in multifactorial CKD, which is
      commonly presented to the nephrologist at stage 4-5, when the kidney is shrunken,
      unstructured and amorphous. As in acute renal injury and despite the lack of
      sensitivity, US-CDI is essential for assessing the progression of renal damage
      and related complications, and for evaluating all conditions that increase the
      risk of CKD, such as lithiasis, recurrent urinary tract infections,
      vesicoureteral reflux, polycystic kidney disease and obstructive nephropathy. The
      timing and frequency of ultrasound scans in CKD patients should be evaluated case
      by case. In this review, we will consider the morpho-functional features of the
      kidney in all nephropathies that may lead to progressive CKD.

PMID- 30191415
TI  - Nodule Size After Chemotherapy and Primary-Tumor Teratoma Components Predict
      Malignancy of Residual Pulmonary Nodules in Metastatic Nonseminomatous Germ Cell
      Tumor.
AB  - BACKGROUND: The treatment goal for visceral metastatic nonseminomatous germ cell
      tumor (NSGCT) is to remove any residual teratoma or viable NSGCT after
      chemotherapy. However, this provides no therapeutic benefit to patients whose
      metastases necrotize on their own. This study therefore analyzed NSGCTs with
      pulmonary metastases to determine preoperative factors that predict necrosis and
      could help identify patients who might be treated with monitoring rather than
      surgery. METHODS: The study retrospectively analyzed 41 patients (135 metastatic
      pulmonary nodules) treated from 1997 to 2016 for NSGCT who showed tumor marker
      normalization after chemotherapy. Relationships between clinicopathologic
      characteristics and necrosis in resected pulmonary specimens were analyzed.
      RESULTS: Receiver operating characteristic analysis of the pulmonary nodules
      showed 9 mm to be the optimal cutoff length for predicting necrosis. The logistic
      regression model showed that absence of teratoma components in the primary tumor
      and all pulmonary nodules shorter than 10 mm after chemotherapy both were
      independent predictors of pathologic necrosis in pulmonary specimens. No patients
      experienced late recurrence (i.e., > 2 years afterward). CONCLUSIONS: The
      presence of teratoma components in primary tumors and nodular size after
      chemotherapy predict the pathology of residual pulmonary nodules. Patients whose
      residual nodules all are shorter than 10 mm and who have no primary-tumor
      teratoma components might be candidates for careful monitoring before pulmonary
      resection.

PMID- 30191414
TI  - Clinical impact of abdominal fat distribution measured by 3-D computed tomography
      volumetry on post-transplant renal function in recipients after living kidney
      transplantation: a retrospective study.
AB  - BACKGROUND: Excessive visceral fat may decrease renal function because of
      metabolic derangements. The aim of this study was to evaluate the impact of
      abdominal fat distribution on renal function of recipients after kidney
      transplantation using the visceral adipose tissue (VAT)/subcutaneous adipose
      tissue (SAT) ratio. METHODS: Seventy-nine patients underwent living kidney
      transplantation from 2009 to 2017. Patients without a correct measurement of VAT
      and SAT, follow-up of < 6 months, or with kidney transplant rejection or a virus
      infection were excluded. VAT and SAT were calculated automatically by 3-D volume
      analyzer software in recipients prior to living kidney transplantation. Our
      primary aim was to identify abdominal fat distribution measured by CT associated
      with renal dysfunction (estimate glomerular filtration rate; eGFR < 45) at 6
      month post renal transplantation in recipient. RESULTS: Fifty-eight living kidney
      recipients were included in this retrospective study: 30 for the high VAT/SAT
      ratio group; 28 for the VAT/SAT low group. Multiple logistic regression analysis
      showed the VAT/SAT ratio and pre-donor eGFR were associated with eGFR < 45
      ml/min/1.73 m2. An increase in VAT/SAT ratio was associated independently with
      the incidence of decreased renal function. CONCLUSION: This finding indicates
      that adipose tissue distribution is an important predictor of the outcome of
      living kidney transplantation in recipients.

PMID- 30191416
TI  - Advanced Imaging for the Diagnosis and Treatment of Coexistent Renal and
      Mullerian Abnormalities.
AB  - PURPOSE OF REVIEW: Abnormal development of the uterus, cervix, and proximal 2/3
      of the vagina results in Mullerian duct anomalies. Because of the close
      embryologic relationship between the developing female genital and urinary
      tracts, abnormalities of the urinary tract often accompany Mullerian duct
      anomalies. Magnetic resonance imaging (MRI) is the current gold standard-imaging
      modality in the evaluation of the anomalies of the female reproductive tract.
      This article discusses the imaging evaluation of Mullerian duct and accompanying
      urinary tract anomalies with a particular focus on the MRI findings. RECENT
      FINDINGS: Several studies have shown high concordance between MRI and three
      dimensional ultrasound (3D US) in the evaluation of Mullerian duct abnormalities.
      3D US is more cost effective than MRI but has not yet been fully substantiated as
      a comparable modality to MRI. Additionally, 3D US does not help elucidate
      concomitant anomalies of the urologic system. Mullerian duct anomalies are often
      associated with abnormalities of the urinary tract. Evaluation with MRI is
      important for the diagnosis of Mullerian duct anomalies and also helps with
      potential surgical planning.

PMID- 30191417
TI  - Immune-Related Adverse Events in Cancer Patients Treated With Immune Checkpoint
      Inhibitors.
AB  - PURPOSE OF REVIEW: With the advent of cancer immunotherapy and immune checkpoint
      inhibitors, patients with malignancies can now achieve durable remissions for
      conditions previously described as terminal. However, immune-related adverse
      events (irAEs) associated with cancer immunotherapy have become an anticipated
      consequence of enhanced T cell activation. Through an extensive literature
      review, we assess the most recent clinical and basic research data concerning
      immune checkpoint blockade and describe the spectrum of associated irAEs as well
      as their management. RECENT FINDINGS: Anti-PD-1, anti-PD-L1, and anti-CTLA-4
      antibodies are widely used in the management of an array of tumors with
      incredible clinical remissions. However, irAEs cause significant morbidity and
      mortality and in some cases, result in withdrawal of cancer therapy and
      initiation of immunosuppression. While this is an exciting time in oncology,
      irAEs are a barrier to adequate care and therefore deserve close attention and
      improved capacity to predict and prevent toxicity. Rheumatologists should be
      familiar with these topics in the eventuality of patient evaluation and
      management.

PMID- 30191418
TI  - Infection of endotheliotropic human cytomegalovirus of trabecular meshwork cells.
AB  - PURPOSE: Human cytomegalovirus (HCMV) infections can cause endotheliitis which is
      associated with an elevation in the intraocular pressure (IOP). However, the
      mechanism of the IOP elevation has not been established. The purpose of this
      study was to determine whether HCMV strains which are capable of infecting
      corneal endothelial cells can also replicate and induce anti-viral responses, and
      can reorganize the actin cytoskeleton in trabecular meshwork cells. STUDY DESIGN:
      Experimental study design. METHODS: Cultured primary human trabecular meshwork
      cells (HTMCs) were infected with the Towne or TB40/E strains of HCMV. TB40/E is
      trophic for vascular endothelial and corneal endothelial cells. Real-time PCR,
      western blot, and fluorescent immunostaining have been used to determine whether
      HCMV-infected HTMCs will support the expression of viral mRNA and protein, allow
      viral replication, and elicit anti-viral host responses. We also determined
      whether lytic replication was present after HCMV infection. RESULTS: HCMV
      infection led to the expression of viral mRNA and proteins of IE1, glycoprotein
      B(gB), and pp65. TB40/E infection induced interferon-beta, a sign of host anti
      viral immune response and monocyte chemotactic protein-1 (MCP-1) as IOP-related
      chemokine. Together with the induction of the regulators of actin cytoskeleton,
      myosin phosphatase Rho interacting protein (MPRIP) and MCP-1, TB40/E induced a
      high level of expression of viral proteins, including IE1, gB, and pp65 as well
      as actin stress fiber formation, and achieved pathogenically high viral titers.
      CONCLUSIONS: Human trabecular meshwork cells support the replication of
      endotheliotropic TB40/E strain of HCMV which indicates that this strain may have
      high virulence for trabecular meshwork.

PMID- 30191419
TI  - Major and minor complications after resection without bowel resection for deeply
      infiltrating endometriosis.
AB  - PURPOSE: To analyze major and minor complications following surgery for deeply
      infiltrating endometriosis including long-term impairment of intestinal, bladder,
      and sexual function. METHODS: Patients who had undergone resection for deeply
      infiltrating endometriosis without anterior rectal resection between 2001 and
      2011 were included (n = 134). Clinical and surgical data, as well as minor and
      major complications, were recorded. A questionnaire was sent to the patients and
      to a healthy control group (n = 100). RESULTS: Major complications occurred in
      3.7% and minor complications in 12.7% of the patients. Surgical revision was
      necessary in five cases. The questionnaire response rate was 66.4%, with a mean
      follow-up period of 75.6 months. Weak urinary flow was reported by 26.4% of the
      patients; a feeling of residual urine by 16.1%; constipation by 13.5%; more than
      one bowel movement/day by 16.9%; insufficient lubrication during intercourse by
      30.3%. The findings for weak urinary flow, feeling of residual urine, and
      insufficient lubrication differed significantly from the control group. Subgroup
      analysis did not identify any statistical associations between questionnaire
      responses and dyspareunia or dysmenorrhea as reasons for surgery, or previous
      endometriosis surgery in the patient's history. CONCLUSIONS: The major and minor
      complication rates were consistent with or lower than the literature data. Few
      studies have investigated complication rates associated with treatment for
      endometriosis in the sacrouterine ligaments and/or the rectovaginal septum. The
      high rates of impaired bladder function and sexual function after endometriosis
      surgery, as well as inadequate data, make further prospective studies on this
      topic necessary.

PMID- 30191420
TI  - Correction to: Recommendations for the management of rheumatoid arthritis in the
      Eastern Mediterranean region: an adolopment of the 2015 American College of
      Rheumatology guidelines.
AB  - In the original version of this article the first name of the co-author was
      incorrectly spelled as "Khaled A. Alnaqbi". The correct spelling should have been
      "Khalid A. Alnaqbi". This is now presented correctly in this article.

PMID- 30191422
TI  - Porcine epidemic diarrhea: an emerging disease in Tibetan pigs in Tibet, China.
AB  - Porcine epidemic diarrhea virus (PEDV) is a devastating cause of diarrhea in pigs
      worldwide, and has caused enormous economic losses in the pork industry. To date,
      however, it is still unclear whether Tibetan pigs from the Tibetan Plateau of
      China are exposed to PED. This study was to investigate the seroprevalence of PED
      in Tibetan pigs in Tibet, China. A total of 364 serum samples were collected from
      Tibetan pigs in Nyingchi in 2014 and 2015. Each sample was assayed for PED
      antibodies by commercial enzyme-linked immunosorbent assay (ELISA) kits. Our
      results showed that the seroprevalence of PED in Tibetan pigs was 39.56% with the
      further distribution of 26.37% and 52.75% in Nyingchi and Mainling (odds ratio
      was more commonly affected in Mainling than Nyingchi), respectively. Moreover,
      the seroprevalence of PED was 65.28%, 35.83%, and 28.57% in juveniles, sub
      adults, and adults, respectively. The prevalence was found as 40.63% in males and
      38.37% in females. The present survey indicated that the infection of PED in
      Tibetan pigs was widely spread in Tibet, which should arouse public concern of
      the threat to the health of Tibetan pigs and the development of breeding industry
      in this unique region of the world.

PMID- 30191421
TI  - Efficacy of certolizumab pegol with and without concomitant use of disease
      modifying anti-rheumatic drugs over 4 years in psoriatic arthritis patients:
      results from the RAPID-PsA randomized controlled trial.
AB  - To report long-term efficacy of certolizumab pegol (CZP) treatment with and
      without concomitant DMARDs in patients with psoriatic arthritis (PsA). RAPID-PsA
      (NCT01087788) was double-blind and placebo-controlled to week 24, dose-blind to
      week 48, and open-label to week 216. Patients had active PsA with >= 1 failed
      DMARD. At baseline, patients were randomized 1:1:1 to CZP 200 mg every 2 weeks:
      CZP 400 mg every 4 weeks: placebo. CZP-randomized patients continued their dose
      into open-label. Observed case efficacy data are reported to week 216 for week 0
      CZP-randomized patients (dose combined) with and without baseline DMARD use
      (DMARD+/DMARD-). Dactylitis (tenderness and >= 10% difference in swelling between
      affected and opposite digits) and enthesitis were measured using Leeds Dactylitis
      Index (LDI) and Leeds Enthesitis Index (LEI). 273/409 randomized patients
      received CZP from baseline: 199/273 (72.9%) DMARD+ and 74/273 (27.1%) DMARD-
      patients. 141/199 (70.9%) DMARD+ and 42/74 (56.8%) DMARD- patients completed Week
      216. DMARD+ (79.7%) and 83.3% of DMARD- patients achieved ACR20 response at week
      216; 79.2 and 78.1% achieved 75% improvement from baseline in Psoriasis Area and
      Severity Index (PASI75). High proportions of DMARD+/DMARD- patients with extra
      articular manifestations at baseline reported total resolution at week 216;
      dactylitis 91.4% of DMARD+ and 93.3% of DMARD- patients, enthesitis 74.4% of
      DMARD+ and 87.5% of DMARD- patients. Long-term improvements in PsA symptoms were
      observed with CZP monotherapy or concomitant DMARDs, across important psoriatic
      disease domains, including joint disease, psoriasis, nail disease, dactylitis,
      and enthesitis.Trial registration: NCT01087788.

PMID- 30191423
TI  - Improved Neural Coding of ITD with Bilateral Cochlear Implants by Introducing
      Short Inter-pulse Intervals.
AB  - Bilateral cochlear implant (CI) users have poor perceptual sensitivity to
      interaural time differences (ITDs), which limits their ability to localize sounds
      and understand speech in noisy environments. This is especially true for high
      rate (> 300 pps) periodic pulse trains, which are used as carriers in CI
      processors. Here, we investigate a novel stimulation strategy in which extra
      pulses are added to high-rate periodic pulse trains to introduce short inter
      pulse intervals (SIPIs). We hypothesized that SIPIs can improve neural ITD
      sensitivity similarly to the effect observed by randomly jittering IPIs (Hancock
      et al., J. Neurophysiol. 108:714-28, 2012). To test this hypothesis, we measured
      ITD sensitivity of single units in the inferior colliculus (IC) of unanesthetized
      rabbits with bilateral CIs. Introducing SIPIs into high-rate pulse trains
      significantly increased firing rates for ~ 60 % of IC neurons, and the extra
      spikes tended to be synchronized to the SIPIs. The additional firings produced by
      SIPIs uncovered latent ITD sensitivity that was comparable to that observed with
      low-rate pulse trains. In some neurons, high spontaneous firing rates masked the
      ITD sensitivity introduced by SIPIs. ITD sensitivity in these neurons could be
      revealed by emphasizing stimulus-synchronized spikes with a coincidence detection
      analysis. Overall, these results with SIPIs are consistent with the effects
      observed previously with jittered pulse trains, with the added benefit of
      retaining control over the timing and number of SIPIs. A novel CI processing
      strategy could incorporate SIPIs by inserting them at selected times to high-rate
      pulse train carriers. Such a strategy could potentially improve ITD perception
      without degrading speech intelligibility and thereby improve outcomes for
      bilateral CI users.

PMID- 30191424
TI  - Surface Motion of Tympanic Membrane in a Chinchilla Model of Acute Otitis Media.
AB  - The conductive hearing loss caused by acute otitis media (AOM) is commonly
      related to a reduction of the tympanic membrane (TM) mobility in response to
      sound stimuli. However, spatial alterations of the TM surface motion associated
      with AOM have rarely been addressed. In this study, the TM surface motion was
      determined using scanning laser Doppler vibrometry (SLDV) in a chinchilla model
      of AOM. The AOM was established by transbullar injection of nontypeable
      Haemophilus influenzae. The TM surface vibration was measured in control
      (uninfected) animals and two AOM groups of animals: 4 days (4D) and 8 days (8D)
      post inoculation. To quantify the effect of middle ear pressure in those infected
      ears, the SLDV measurement was first conducted in unopened AOM ears and then in
      middle ear pressure released ears. Results showed that middle ear infection
      generally reduced the TM displacement across the entire surface, but the
      reduction in the umbo displacement over the time course, from 4 to 8 days post
      inoculation, was less than the reduction in the displacement at the center of
      each quadrant. The presence of middle ear fluid shifted the occurrence of
      traveling-wave-like motion on the TM surface to lower frequencies. The
      observation of the spatial variations of TM surface motion from this study will
      help refine our understanding of the middle ear sound transmission
      characteristics in relation to AOM.

PMID- 30191425
TI  - Noise-Induced Hypersensitization of the Acoustic Startle Response in Larval
      Zebrafish.
AB  - Overexposure to loud noise is known to lead to deficits in auditory sensitivity
      and perception. We studied the effects of noise exposure on sensorimotor
      behaviors of larval (5-7 days post-fertilization) zebrafish (Danio rerio),
      particularly the auditory-evoked startle response and hearing sensitivity to
      acoustic startle stimuli. We observed a temporary 10-15 dB decrease in startle
      response threshold after 18 h of flat-spectrum noise exposure at 20 dB re.1 ms-2.
      Larval zebrafish also exhibited decreased habituation to startle-inducing stimuli
      following noise exposure. The noise-induced sensitization was not due to changes
      in absolute hearing thresholds, but was specific to the auditory-evoked escape
      responses. The observed noise-induced sensitization was disrupted by AMPA
      receptor blockade using DNQX, but not NMDA receptor blockade. Together, these
      experiments suggest a complex effect of noise exposure on the neural circuits
      mediating auditory-evoked behaviors in larval zebrafish.

PMID- 30191426
TI  - The Stress Response in the Non-sensory Cells of the Cochlea Under Pathological
      Conditions-Possible Role in Mediating Noise Vulnerability.
AB  - Various stressors, such as loud sounds and the effects of aging, impair the
      function and viability of the cochlear sensory cells, the hair cells. Stressors
      trigger pathophysiological changes in the cochlear non-sensory cells as well. We
      have here studied the stress response mounted in the lateral wall of the cochlea
      during acute noise stress and during age-related chronic stress. We have used the
      activation of JNK/c-Jun, ERK, and NF-kappaB pathways as a readout of the stress
      response, and the expression of the FoxO3 transcription factor as a possible
      additional player in cellular stress. In the aging cochlea, NF-kappaB
      transcriptional activity was strongly induced in the stria vascularis of the
      lateral wall. This induction was linked with the atrophy of the stria vascularis,
      suggesting a role for NF-kappaB signaling in mediating age-related strial
      degeneration. Acutely following noise exposure, the JNK/c-Jun, ERK, and NF-kappaB
      pathways were activated in the spiral ligament of the lateral wall of CBA/Ca
      mice. This activation was concomitant with the morphological transformation of
      macrophages, suggesting that the upregulation of stress signaling leads to
      macrophage activation. In contrast, C57BL/6J mice lacked these responses. Only
      the combination of noise exposure and a systemic stressor, lipopolysaccharide,
      exceeded the threshold for the activation of stress signaling in the lateral wall
      of C57BL/6J mice. In addition, we found that, at the young adult age, outer hair
      cells of CBA/Ca mice are much more vulnerable to loud sounds compared to these
      cells of C57BL/6J mice. These results suggest that the differential stress
      response in the lateral wall of the two mouse strains underlies, in part, the
      differential noise vulnerability of their outer hair cells. Together, we propose
      that the molecular stress response in the lateral wall modulates the outcome of
      the stressed cochlea.

PMID- 30191427
TI  - Diffuse double-layer structure in mixed electrolytes considering ions as
      dielectric spheres.
AB  - The structure of the diffuse part of the electric double layer at solid
      electrolyte solution interfaces is examined using a theoretical model that takes
      into account the finite ion size by modeling the solution as a suspension of
      polarizable insulating spheres in water. This formalism is applied to mixed
      electrolyte solutions using the "Boublik-Mansoori-Carnahan-Starling-Leland"
      (BMCSL) theory for the steric interactions among ions. It is shown that the ionic
      size differences have a strong bearing on the diffuse part of the electric double
      layer structure of these systems. Moreover, for strong potential values, the
      different size-related effects become important even for binary electrolyte
      solutions due to the presence of H+ and OH- ions that are substantially smaller
      than hydrated ions originated from salt dissociation. The obtained results
      display some of the qualitative features observed in experiments on aqueous
      systems that are generally interpreted in terms of totally different mechanisms.

PMID- 30191428
TI  - Electrochemical skin conductance to measure sudomotor function: the importance of
      not misinterpreting the evidence.

PMID- 30191429
TI  - Bacteriophage-resistant industrial fermentation strains: from the cradle to
      CRISPR/Cas9.
AB  - Bacteriophage contamination and cell lysis have been recurring issues with some
      actinomycetes used in the pharmaceutical fermentation industry since the
      commercialization of streptomycin in the 1940s. In the early years, spontaneous
      phage-resistant mutants or lysogens were isolated to address the problem. In some
      cases, multiple phages were isolated from different contaminated fermentors, so
      strains resistant to multiple phages were isolated to stabilize the fermentation
      processes. With the advent of recombinant DNA technology, the early scaleup of
      the Escherichia coli fermentation process for the production of human insulin A
      and B chains encountered contamination with multiple coliphages. A genetic
      engineering solution was to clone and express a potent restriction/modification
      system in the production strains. Very recently, an E. coli fermentation of 1,3
      propanediol was contaminated by a coliphage related to T1. CRISPR/Cas9 technology
      was applied to block future contamination by targeting seven different phage
      genes for double-strand cleavage. These approaches employing spontaneous
      mutation, genetic engineering, and synthetic biology can be applied to many
      current and future microorganisms used in the biotechnology industry.

PMID- 30191431
TI  - Adverse Reactions in Antifolate-Treated Toxoplasmic Retinochoroiditis.
AB  - This study seeks to define factors affecting the development of adverse reactions
      to intensive therapy of toxoplasmic retinochoroiditis with antifolate agents
      (pyrimethamine/sulfadoxine) and antibiotics followed by secondary antifolate
      prophylaxis. The study was of retrospective and observational nature. Medical
      files were reviewed of 551 patients suffering from ocular toxoplasmosis during
      1994-2013. All patients were treated with the same protocol: 3-week intensive
      pyrimethamine/sulfadoxine plus antibiotic/steroid therapy. Three hundred and
      fourteen out of the 551 patients qualified for the subsequent 6-month long
      secondary antifolate prophylaxis. The type and occurrence rate of adverse
      reactions were taken into account. The probability of an adverse reaction during
      the intensive therapy phase was 33.4%. Hypertransaminasemia was the most common
      event observed in 24.6% of the patients, but it assumed a severe character in
      just 0.9%, with male gender and age over 25 years being the predisposing factors.
      Less common adverse effects included thrombocytopenia (8.3%), hypersensitivity
      skin reactions (3.0%), and abdominal pain (1.4%). The adverse effects of
      secondary antifolate prophylaxis, most commonly hypersensitivity skin reactions
      and hypertransaminasemia, followed by thrombocytopenia and abdominal pain, were
      observed in 4.9% of the patients. Ten of them (2.7%) had to discontinue the
      treatment while eight others continued with pyrimethamine alone without further
      adverse effects, which suggests that discontinuation of the sulfonamide decreased
      the propensity for adverse reactions. The treatment strategy in these patients
      differed from previous reports in that it used lower doses of
      pyrimethamine/sulfonamide, with no folinic acid supplementation. Nonetheless, the
      rate and severity of adverse events were no greater than those noticed with
      traditional regimens, with higher antifolate doses and folinic acid
      supplementation. We conclude that the dose and drug-mitigated treatment strategy
      we employed deserves consideration as a promising alternative to traditional
      treatments for ocular toxoplasmosis.

PMID- 30191430
TI  - Heterologous production of a new lasso peptide brevunsin in Sphingomonas
      subterranea.
AB  - A shuttle vector pHSG396Sp was constructed to perform gene expression using
      Sphingomonas subterranea as a host. A new lasso peptide biosynthetic gene
      cluster, derived from Brevundimonas diminuta, was amplified by PCR and integrated
      to afford a expression vector pHSG396Sp-12697L. The new lasso peptide brevunsin
      was successfully produced by S. subterranea, harboring the expression vector,
      with a high production yield (10.2 mg from 1 L culture). The chemical structure
      of brevunsin was established by NMR and MS/MS experiments. Based on the
      information obtained from the NOE experiment, the three-dimensional structure of
      brevunsin was determined, which indicated that brevunsin possessed a typical
      lasso structure. This expression vector system provides a new heterologous
      production method for unexplored lasso peptides that are encoded by bacterial
      genomes.

PMID- 30191432
TI  - The effects of land cover change on carbon stock dynamics in a dry Afromontane
      forest in northern Ethiopia.
AB  - BACKGROUND: Forests play an important role in mitigating global climate change by
      capturing and sequestering atmospheric carbon. Quantitative estimation of the
      temporal and spatial pattern of carbon storage in forest ecosystems is critical
      for formulating forest management policies to combat climate change. This study
      explored the effects of land cover change on carbon stock dynamics in the Wujig
      Mahgo Waren forest, a dry Afromontane forest that covers an area of 17,000 ha in
      northern Ethiopia. RESULTS: The total carbon stocks of the Wujig Mahgo Waren
      forest ecosystems estimated using a multi-disciplinary approach that combined
      remote sensing with a ground survey were 1951, 1999, and 1955 GgC in 1985, 2000
      and 2016 years respectively. The mean carbon stocks in the dense forests, open
      forests, grasslands, cultivated lands and bare lands were estimated at 181.78 +/-
      27.06, 104.83 +/- 12.35, 108.77 +/- 6.77, 76.54 +/- 7.84 and 83.11 +/- 8.53 MgC
      ha-1 respectively. The aboveground vegetation parameters (tree density, DBH and
      height) explain 59% of the variance in soil organic carbon. CONCLUSIONS: The
      obtained estimates of mean carbon stocks in ecosystems representing the major
      land cover types are of importance in the development of forest management plan
      aimed at enhancing mitigation potential of dry Afromontane forests in northern
      Ethiopia.

PMID- 30191433
TI  - Antennal Olfactory Physiology and Behavior of Males of the Ponerine Ant
      Harpegnathos saltator.
AB  - In comparison to the large amount of study on the communication abilities of
      females in ant societies and their associated chemical ecology and sensory
      physiology, such study of male ants has been largely ignored; accordingly, little
      is known about their olfactory sensory capabilities. To address this, we explored
      peripheral odor sensitivities in male Harpegnathos saltator by measuring the
      electrophysiological activity of olfactory sensory neurons within antennal
      trichoid and coeloconic sensilla using an extracellular recording technique. In
      an initial trial of 46 compounds, sensilla trichodea responded strongly to two
      alarm pheromone components, while a limited number of non-hydrocarbon odorants
      elicited strong responses in sensilla coeloconica. Both sensillar types responded
      indifferently to 31 cuticular hydrocarbons (CHCs) and synthetic long-chain
      hydrocarbons (HCs) typically found on insect cuticle. In a search for sensilla
      responding to CHCs and other compounds, we found some sensilla that responded to
      synthetic HCs and CHCs from virgin queen postpharyngeal glands that are
      potentially used in close range mate recognition. Olfactometer bioassays of male
      ants to 15 non-HCs correlated sensory responsiveness to the respective behavioral
      responses. Comparing olfactory responses between H. saltator males and females,
      we found that sensilla coeloconica and basiconica of workers showed greater
      responses and broader selectivity to all compounds. The rarity of CHC-responding
      trichoid sensilla in Harpegnathos males suggests a more specific role in sexual
      communication compared to that in females, which use CHCs in a broader
      communication context.

PMID- 30191434
TI  - Pollinator Preferences for Floral Volatiles Emitted by Dimorphic Anthers of a
      Buzz-Pollinated Herb.
AB  - Floral scents attract pollinators to plant rewards; in nectarless flowers, pollen
      grains are the only reward. Thus, pollen not only fertilizes ovules, but also
      feeds pollinators. This dilemma is resolved by specialization of anthers (i.e.,
      heteranthery): feeding anthers that feed pollinators and pollinating anthers for
      fertilization. We hypothesized that the chemical composition of floral volatiles
      differs between the two types of anther and influences pollination preference for
      feeding anthers. We used Solanum rostratum as a study model because its
      heterantherous flowers produce a floral scent that suggests a close association
      with their pollinators. The main aim of this study was to determine the chemical
      composition of the two types of anther and to investigate how they influence
      foraging behaviour of pollinators. To characterize this composition, we used
      solid phase microextraction and hexane extraction followed by gas chromatography
      mass spectrometry. We registered 12 volatile compounds in S. rostratum floral
      extracts, mainly aromatic and sesquiterpene compounds. The proportion of these
      compounds differed between feeding and pollinating anthers. Some of these
      compounds were probably emitted by osmophores located in both anther types. Also,
      we used electroantennography to investigate Melipona solani antennal response to
      floral volatiles. The M. solani antennae are receptive to the highest floral
      extract dose tested. Finally, we conducted two behavioural bioassays to test bee
      attraction for each type of floral extract: a) multiple-choice in a feeding arena
      using M. solani and b) Y-olfactometer bioassay using Bombus impatiens. Both bee
      species preferred feeding anthers in bioassays. In conclusion, heteranthery
      involves chemical differentiation (i.e., proportion of volatiles compounds) in
      anther specialization that influences bee preference for feeding anthers over
      pollinating anthers.

PMID- 30191437
TI  - Is having a sweetheart enough to survive?

PMID- 30191435
TI  - Sleep quality buffers the effects of negative social interactions on maternal
      mood in the 3-6 month postpartum period: a daily diary study.
AB  - Sleep and social relationships are two key determinants of psychosocial health
      that undergo considerable change across the transition to motherhood. The current
      study investigated the bidirectional relationship between daytime Positive and
      Negative Social Interactions (PSIs & NSIs) and nighttime sleep quality on
      maternal mood across 1 week in the 3-6 month postpartum period. Sixty healthy,
      non-depressed first-time mothers completed 7-consecutive days of daily social
      interaction and sleep diaries. Results indicated that higher than average sleep
      quality buffered the effect of higher than average NSIs on maternal mood (i.e.,
      buffered mood reactivity) and appeared to promote mood recovery following a
      particularly "bad day" (i.e., higher than average NSIs). In addition, although
      PSIs were more common than NSIs overall, the most frequent and positively rated
      PSIs were with baby as were the most frequent and negatively rated NSIs. To our
      knowledge, our results are the first to characterize the impact of PSIs on
      postpartum maternal mood, assess maternal-infant social interactions in daily
      diary study of postpartum social relationships, and demonstrate the role that
      maternal sleep quality plays in social discord-related mood reactivity and mood
      recovery processes in the 3-6 month postpartum period.

PMID- 30191436
TI  - Unequal misses during the flash-induced advancement of photosystem II: effects of
      the S state and acceptor side cycles.
AB  - Photosynthetic water oxidation is catalyzed by the oxygen-evolving complex (OEC)
      in photosystem II (PSII). This process is energetically driven by light-induced
      charge separation in the reaction center of PSII, which leads to a stepwise
      accumulation of oxidizing equivalents in the OEC (Si states, i = 0-4) resulting
      in O2 evolution after each fourth flash, and to the reduction of plastoquinone to
      plastoquinol on the acceptor side of PSII. However, the Si-state advancement is
      not perfect, which according to the Kok model is described by miss-hits (misses).
      These may be caused by redox equilibria or kinetic limitations on the donor (OEC)
      or the acceptor side. In this study, we investigate the effects of individual S
      state transitions and of the quinone acceptor side on the miss parameter by
      analyzing the flash-induced oxygen evolution patterns and the S2, S3 and S0 state
      lifetimes in thylakoid samples of the extremophilic red alga Cyanidioschyzon
      merolae. The data are analyzed employing a global fit analysis and the results
      are compared to the data obtained previously for spinach thylakoids. These two
      organisms were selected, because the redox potential of QA/QA- in PSII is
      significantly less negative in C. merolae (Em = - 104 mV) than in spinach (Em = -
      163 mV). This significant difference in redox potential was expected to allow the
      disentanglement of acceptor and donor side effects on the miss parameter. Our
      data indicate that, at slightly acidic and neutral pH values, the Em of QA-/QA
      plays only a minor role for the miss parameter. By contrast, the increased energy
      gap for the backward electron transfer from QA- to Pheo slows down the charge
      recombination reaction with the S3 and S2 states considerably. In addition, our
      data support the concept that the S2 -> S3 transition is the least efficient step
      during the oxidation of water to molecular oxygen in the Kok cycle of PSII.

PMID- 30191438
TI  - Multiparametric assessment of left atrial remodeling using 18F-FDG PET/CT cardiac
      imaging: A pilot study.
AB  - BACKGROUND: Left atrial (LA) remodeling is associated with structural, electric,
      and metabolic LA changes. Integrated evaluation of these features in vivo is
      lacking. METHODS: Patients undergoing 18F-fluorodeoxyglucose (FDG) PET-CT during
      a hyperinsulinemic-euglycemic clamp were classified into sinus rhythm (SR),
      paroxysmal AF (PAF), and persistent AF (PerAF). The LA was semiautomatically
      segmented, and global FDG uptake was quantified using standardized uptake values
      (SUVmax and SUVmean) in gated, attenuation-corrected images and normalized to LA
      blood pool activity. Regression was used to relate FDG data to AF burden and
      critical patient factors. Continuous variables were compared using t-tests or
      Mann-Whitney tests. RESULTS: 117 patients were included (76% men, age 66.4 +/-
      11.0, ejection fraction (EF) 25[22-35]%) including those with SR (n = 48), PAF (n
      = 55), and PerAF (n = 14). Patients with any AF had increased SUVmean (2.3[1.5
      2.4] vs 2.0[1.5-2.5], P = 0.006), SUVmax (4.4[2.8-6.7] vs 3.2[2.3-4.3], P <
      0.001), uptake coefficient of variation (CoV) 0.28[0.22-0.40] vs 0.25[0.2-0.33],
      P < 0.001), and hypometabolic scar (32%[14%-53%] vs 16.5%[0%-38.5%], P = 0.01).
      AF burden correlated with increased SUVmean, SUVmax, CoV, and scar independent of
      age, gender, EF, or LA size (P < 0.03 for all). CONCLUSIONS: LA structure and
      metabolism can be assessed using FDG PET/CT. Greater AF burden correlates with
      the increased LA metabolism and scar.

PMID- 30191439
TI  - Mycoplasma contamination of leukemic cell lines alters protein expression
      determined by reverse phase protein arrays.
AB  - Mycoplasma contamination is a major problem in cell culturing, potentially
      altering the results of cell line-based experiments in largely uncharacterized
      ways. To define the consequences of mycoplasma infection at the level of protein
      expression we utilized the reverse phase protein array technology to analyze the
      expression of 235 proteins in mycoplasma infected, uninfected post treatment, and
      never-infected leukemic cell lines. Overall, protein profiles of cultured cells
      remained relatively stable after mycoplasma infection. However, paired
      comparisons for individual proteins identified that 18.7% of the proteins
      significantly changed between the infected and the never-infected cell line
      samples, and that 14.0% of the proteins significantly altered between the
      infected and the post treatment samples. Six percent of the proteins were
      affected in the post treatment samples compared to the never-infected samples,
      and 7.2% compared to treated cells that had never had mycoplasma infection
      before. Proteins that were significantly altered in the infected cells were
      enriched for apoptotic signaling processes and auto-phosphorylation, suggesting
      an increased cellular stress and a decreased growth rate. In conclusion, this
      study shows that mycoplasma infection of leukemic cell lines alters the proteins
      expression levels, potentially confounding experimental results. This reinforces
      the need for regular testing of mycoplasma.

PMID- 30191440
TI  - Sequence-guided approach to genotyping plant clones and species using polymorphic
      NB-ARC-related genes.
AB  - KEY MESSAGE: Leveraging the heightened levels of polymorphism in NB-ARC-related
      protein encoding genes in higher plants, a bioinformatic pipeline was created to
      identify regions in this gene family from sequenced plant genomes that exhibit
      fragment length or single nucleotide differences in different accessions of the
      same species. Testing this approach with the aquatic plant Spirodela polyrhiza
      demonstrated its superior performance in comparison with currently available
      genotyping technologies based on PCR amplification. Rapid and economical
      genotyping tools that can reliably distinguish species and intraspecific
      variations in plants can be powerful tools for biogeographical and ecological
      studies. Clones of the cosmopolitan duckweed species, Spirodela polyrhiza, are
      difficult to distinguish morphologically due to their highly abbreviated
      architecture and inherently low levels of sequence variation. The use of
      plastidic markers and generic Amplification Fragment Length Polymorphism
      approaches have met with limited success in resolving clones of S. polyrhiza from
      diverse geographical locales. Using whole genome sequencing data from nine S.
      polyrhiza clones as a training set, we created an informatic pipeline to identify
      and rank polymorphic regions from nuclear-encoded NB-ARC-related genes to design
      markers for PCR, Sanger sequencing (barcoding), and fragment length analysis.
      With seven primer sets, we found 21 unique fingerprints from a set of 23 S.
      polyrhiza clones. However, three of these clones share the same fingerprint and
      are indistinguishable by these markers. These primer sets can also be used as
      interspecific barcoding tools to rapidly resolve S. polyrhiza from the closely
      related S. intermedia species without the need for DNA sequencing. Our work
      demonstrates a general approach of using hyper-polymorphic loci within genomes as
      a resource to produce facile tools that can have high resolving power for
      genotyping applications.

PMID- 30191442
TI  - Assessment of hair cortisol in euthyroid, hypothyroid, and subclinical
      hypothyroid subjects.
AB  - PURPOSE: Hypothyroidism is associated with an increase in serum cortisol level
      while the long-term activity of hypothalamic-pituitary-adrenal (HPA) axis in
      hypothyroid, and subclinical hypothyroid (SCH) subjects has not been studied.
      This study aimed to assess the hair cortisol levels as a long-term activity of
      HPA axis in hypothyroid, SCH and a group of healthy adult subjects. Also, it
      aimed to examine the correlation of hair cortisol levels with hypothalamic
      pituitary-thyroid (HPT) axis and anthropometric measures. METHODS: We
      prospectively evaluated a group of normal, SCH and hypothyroid subjects. Serum
      TSH, FT4, and FT3 were measured as a component of the HPT axis. Hair samples were
      collected, prepared, followed by extraction of hair cortisol and measurement in
      pg/mg of hair. Hair cortisol levels were compared in normal, SCH and hypothyroid
      groups and correlated with HPT axis and anthropometric data. RESULTS: A total of
      65 healthy volunteers were analyzed, and the mean hair cortisol level was
      reported to be 17.38 pg/mg of hair. Hair cortisol level was slightly higher in
      the SCH subjects, 18.19 pg/mg of hair; however the difference was not
      significant. Compared to the euthyroid subject, a significantly higher hair
      cortisol level was recorded in the hypothyroid subjects, 24.17 pg/mg hair, p <
      .05. Hair cortisol was significantly and positively associated with each of the
      serum TSH, age, weight and BMI (p < .05). CONCLUSIONS: Overt hypothyroidism but
      not SCH is significantly associated with higher hair cortisol levels compared to
      normal subjects, and a significant relation between hair cortisol with HPT axis
      was found. Also, weight and BMI were positively correlated with hair cortisol
      level.

PMID- 30191441
TI  - Oral glucose load and mixed meal feeding lowers testosterone levels in healthy
      eugonadal men.
AB  - PURPOSE: Precise evaluation of serum testosterone levels is important in making
      an accurate diagnosis of androgen deficiency. Recent practice guidelines on male
      androgen deficiency recommend that testosterone be measured in the morning while
      fasting. Although there is ample evidence regarding morning measurement of
      testosterone, studies that evaluated the effect of glucose load or meals were
      limited by inclusion of hypogonadal or diabetic men, and measurement of
      testosterone was not performed using mass spectrometry. METHODS: Sixty men (23-97
      years) without pre-diabetes or diabetes who had normal total testosterone (TT)
      levels underwent either an oral glucose tolerance test (OGTT) or a mixed meal
      tolerance test (MMTT) after an overnight fast. Serum samples were collected
      before and at regular intervals for 2 h (OGTT cohort) or 3 h (MMTT cohort). TT
      was measured by LC-MS/MS. LH and prolactin were also measured. RESULTS: TT
      decreased after a glucose load (mean drop at nadir = 100 ng/dL) and after a mixed
      meal (drop at nadir = 123 ng/dL). Approximately 11% of men undergoing OGTT and
      56% undergoing MMTT experienced a transient decrease in TT below 300 ng/dL, the
      lower normal limit. Testosterone started declining 20 min into the tests, with
      average maximum decline at 60 min. Most men still had TT lower than baseline at
      120 min. This effect was independent of changes in LH or prolactin. CONCLUSION: A
      glucose load or a mixed meal transiently, but significantly, lowers TT levels in
      healthy, non-diabetic eugonadal men. These findings support the recommendations
      that measurement of serum testosterone to diagnose androgen deficiency should be
      performed while fasting.

PMID- 30191443
TI  - Interactions between hypothalamic pituitary thyroid axis and other pituitary
      dysfunctions.
AB  - Central hypothyroidism is defined as low circulating free thyroxine (free T4)
      with inappropriately low circulating thyrotropin (TSH), in context of a
      hypothalamic pituitary pathology. Rare cases of idiopathic central hypothyroidism
      caused by a functional defect may occur, and the condition is often overlooked
      due to difficulty in achieving the correct diagnosis, sparse symptomatology of
      the condition and a high risk of misinterpretion of the biochemical changes in
      central hypothyroidism. Central hypothyroidism is mainly seen in patients with
      hypothalamic-pituitary pathology due to one of many possible aetiologies, where
      other hormone deficiencies often co-exist, and both the presence of other
      deficiencies and their replacement have a strong influence on the measurement of
      the thyroid-related hormones and thereby interpretation of the thyroid function
      variables in relation to the clinical impact of thyroid hormone substitution
      therapy. Conversely, lack of thyroid hormone has a similar strong influence on
      the interpretation of other pituitary hormone axes, as well as their replacement.
      Undertreating patients with central hypothyroidism may have serious metabolic
      consequences with a potentially increased risk of cardiovascular morbidity. The
      present review thus aims at describing central hypothyroidism, by an overview of
      interactions of hypothyroidism with other pituitary hormones, diagnosing/testing
      for central hypothyroidism, and focusing on consequences of undertreatment.
      Finally, it is mentioned how to deal with new diagnostic settings with lower a
      priori likelihood of hypopituitarism, particularly in view of the importance of
      stringent diagnostic testing in order to avoid overdiagnosing central
      hypothyroidism.

PMID- 30191444
TI  - Ambient particulate matter concentration levels of Ahvaz, Iran, in 2017.
AB  - Dust storm in Khuzestan region is strongly influenced by transportation and
      influx of large amount of particulate matter from internal sources (Hawizeh
      Marshes and East Ahwaz) and external sources (the Arabian Desert in Saudi Arabia,
      Jordan, Syria and the Sahara Desert). Particulate matter is one of the main
      components of indoor and outdoor air quality that can be very dangerous for
      human. The principal objective of this study was the pinpoint of the source of
      airborne particulate matter by the NOAA HYSPLIT model in Ahvaz City, southwest of
      Iran. The investigation of dust storm and their origin was performed by the GFSG
      Meteorological Data (backward trajectories ending analysis of the NOAA HYSPLIT
      model) and collecting particulate samples with high-volume air samplers during
      the fall and winter seasons. The results showed the average ambient particulate
      matter concentration in the cold and warm seasons was 158 and 161 ug/m3,
      respectively. Moreover, the average particulate matter concentration in the cold
      season was significantly higher than the standard level as presented in the
      National Ambient Air Quality Standard. Consequently, it seems essential to
      develop green space, decrease particulate emission from source and make
      determined efforts to control dust at governmental and international scales.

PMID- 30191446
TI  - Incidence rate of physical and verbal violence inflicted by patient and their
      companions on the radiology department staff of educational hospitals of medical
      university, Kermanshah, 2017.
AB  - INTRODUCTION: Regarding the increasing risk of violence toward employees in
      diagnostic and therapeutic centers, radiology staff members are often exposed to
      forms of violence through direct contact with patients and with many professional
      stresses. The aim of this study is to investigate the causes and incidence of
      violence against radiographers in radiology departments of educational centers
      and hospitals. MATERIALS AND METHODS: In this descriptive-analytic study,
      violence incidence was investigated in all 121 radiographers working in radiology
      departments of educational centers of Kermanshah in 2016. Data were collected by
      a reliable and stable researcher-made questionnaire. Data analysis was also
      performed using descriptive statistics and T test and Chi-square tests by STATA
      11 software. RESULTS: The results showed that 72.7% of radiographers had
      experienced violence in their work environment. Verbal violence (77.3%) was the
      most prevalent type where patient accompaniments were the most frequent cause of
      violence (54.7%), most of the violence incidents were at night shift (43.6%) and
      over-crowdedness was the most common cause of violence in the radiology
      department (21.0%). The verbal violence against radiographers younger than 40 was
      significantly higher (P = 0.04) than the age group above 40 years. CONCLUSION:
      The incidence of verbal violence against radiographers in radiology departments
      is high which can be reduced by providing adequate human resource and equipment
      in radiology departments, re-training courses on the prevention and management of
      violent behavior and the suing the violent events against radiologists.

PMID- 30191445
TI  - Identification of the most significant magnetic resonance imaging (MRI) radiomic
      features in oncological patients with vertebral bone marrow metastatic disease: a
      feasibility study.
AB  - OBJECTIVES: Recently, radiomic analysis has gained attention as a valuable
      instrument for the management of oncological patients. The aim of the study is to
      isolate which features of magnetic resonance imaging (MRI)-based radiomic
      analysis have to be considered the most significant predictors of metastasis in
      oncological patients with spinal bone marrow metastatic disease. MATERIALS AND
      METHODS: Eight oncological patients (3 lung cancer; 1 prostatic cancer; 1
      esophageal cancer; 1 nasopharyngeal cancer; 1 hepatocarcinoma; 1 breast cancer)
      with pre-radiotherapy MR imaging for a total of 58 dorsal vertebral bodies, 29
      metastatic and 29 non-metastatic were included. Each vertebral body was contoured
      in T1 and T2 weighted images at a radiotherapy delineation console. The obtained
      data were transferred to an automated data extraction system for morphological,
      statistical and textural analysis. Eighty-nine features for each lesion in both
      T1 and T2 images were computed as the median of by-slice values. A Wilcoxon test
      was applied to the 89 features and the most statistically significant of them
      underwent to a stepwise feature selection, to find the best performing predictors
      of metastasis in a logistic regression model. An internal cross-validation via
      bootstrap was conducted for estimating the model performance in terms of the area
      under the curve (AUC) of the receiver operating characteristic. RESULTS: Of the
      89 textural features tested, 16 were found to differ with statistical
      significance in the metastatic vs non-metastatic group. The best performing model
      was constituted by two predictors for T1 and T2 images, namely one morphological
      feature (center of mass shift) (p value < 0.01) for both datasets and one
      histogram feature minimum grey level (p value < 0.01) for T1 images and one
      textural feature (grey-level co-occurrence matrix joint variance (p value < 0.01)
      for T2 images. The internal cross-validation showed an AUC of 0.8141 (95% CI
      0.6854-0.9427) in T1 images and 0.9116 (95% CI 0.8294-0.9937) in T2 images.
      CONCLUSIONS: The results suggest that MRI-based radiomic analysis on oncological
      patients with bone marrow metastatic disease is able to differentiate between
      metastatic and non-metastatic vertebral bodies. The most significant predictors
      of metastasis were found to be based on T2 sequence and were one morphological
      and one textural feature.

PMID- 30191447
TI  - Contrast analysis of the relationship between the HRCT sign and new pathologic
      classification in small ground glass nodule-like lung adenocarcinoma.
AB  - PURPOSE: To perform contrast analysis of the relationship between high-resolution
      computed tomography (HRCT) signs and new pathologic classification of small GGNs
      like lung adenocarcinoma. MATERIALS AND METHODS: The HRCT data from 145
      pathologically confirmed cases of small GGNs of lung adenocarcinoma were analysed
      retrospectively. The 145 cases of GGNs were divided into pre-invasive (PI) group
      (n = 46), micro-invasive adenocarcinoma (MIA) group (n = 48), and invasive
      adenocarcinoma (IAC) group (n = 51). HRCT imaging sign of GGNs in each group was
      assessed and compared. RESULTS: Significant differences in GGN size were found
      among the three groups (P < 0.05). The presence of a tumour-lung interface in the
      MIA and IAC groups was significantly higher than that in the PI group (P < 0.05),
      but no significant difference was found between the MIA and IAC groups. The
      presence of a pleural indentation sign in the IAC group was significantly higher
      than that in the other two groups (P < 0.05), but no significant difference was
      noted between the latter two groups. Significant differences were found in the
      lobulated and spicule signs among the three groups (P < 0.05). The presence of a
      microvascular sign in the MIA and IAC groups was significantly higher than that
      in the PI group (P < 0.05). No significant difference was found in the GGN
      density, vacuole sign, air bronchus sign and notch sign among the three groups.
      CONCLUSIONS: The HRCT signs of GGNs could be used to differentiate among pre
      invasive lesions, micro-invasive lesions and invasive lung adenocarcinoma.

PMID- 30191449
TI  - Noninvasive Monitoring of Dynamic Cerebrovascular Autoregulation and 'Optimal
      Blood Pressure' in Normal Adult Subjects.
AB  - BACKGROUND: Cerebrovascular autoregulation can be continuously monitored from
      slow fluctuations of arterial blood pressure (ABP) and regional cerebral oxygen
      saturation (rSO2). The purpose of this study was to evaluate the index of dynamic
      cerebrovascular autoregulation (TOx) and the associated 'optimal' ABP in normal
      adult healthy subjects. METHODS: Twenty-eight healthy volunteers were studied.
      TOx was calculated as the moving correlation coefficient between spontaneous
      fluctuations of ABP and rSO2. ABP was measured with the Finometer
      photoplethysmograph. The ABP with optimal autoregulation (ABPOPT) was also
      determined as the ABP level with the lowest associated TOx (opt-TOx). RESULTS:
      Average rSO2 and TOx was 72.3 +/- 2.9% and 0.05 +/- 0.18, respectively. Two
      subjects had impaired autoregulation with a TOx > 0.3. The opt-TOx was - 0.1 +/-
      0.26. ABPOPT was 87.0 +/- 16.7 mmHg. The difference between ABP and ABPOPT was -
      0.3 +/- 7.5 mmHg. In total, 44% of subjects had a deviation of ABP from ABPOPT
      exceeding 5 mmHg. ABPOPT ranged from 57 to 117 mmHg. CONCLUSIONS: TOx in healthy
      volunteers on average displays intact autoregulation and ABP close to ABPOPT.
      However, some subjects have possible autoregulatory dysfunction or a significant
      deviation of ABP from ABPOPT, which may confer a susceptibility to neurological
      injury.

PMID- 30191450
TI  - Methodological Reasons for the Association Between Hypocalcemia and Worse
      Outcomes in Intracranial Hemorrhage.

PMID- 30191448
TI  - Percutaneous management of bone metastases: state of the art, interventional
      strategies and joint position statement of the Italian College of MSK Radiology
      (ICoMSKR) and the Italian College of Interventional Radiology (ICIR).
AB  - Interventional radiology provides local management of bone metastases (BM) with a
      palliative intent in most cases, or with a curative intent in selected patients.
      Its role has rapidly expanded in the last decade, offering new treatment
      solutions often in combination with surgery, radiation therapy and medical
      treatments. The aim of the present paper is to increase awareness, acceptance and
      adoption of interventional radiology procedures for the treatment of BM; and to
      present the joint position of the Italian College of Musculoskeletal Radiology
      and the Italian College of Interventional Radiology.

PMID- 30191451
TI  - Can Macromolecular Nitroxide Work as Extracellular Superoxide Dismutase Mimetic
      in Cancer and Stroke Therapy?

PMID- 30191452
TI  - The Iron State in Spleen and Liver Tissues from Patients with Hematological
      Malignancies Studied Using Magnetization Measurements and Mossbauer Spectroscopy.
AB  - In this overview, we present the results of the study of spleen and liver tissues
      taken from healthy donors in comparison with those from patients with (i) non
      Hodgkin B-cell lymphomas, namely, mantle cell lymphoma and marginal zone B-cell
      lymphoma, (ii) acute myeloid leukemia, and (iii) primary myelofibrosis. The study
      was carried out using Mossbauer spectroscopy and magnetization measurements for
      the analysis of ferritin-like iron in spleen and liver tissues. Magnetization
      measurements demonstrated small differences in the saturation magnetic moments
      and revealed additional paramagnetic components. Two liver samples demonstrated
      unusual behavior of the magnetic moment when the zero-field-cooled curve was over
      the field-cooled curve in the temperature range between ~40 and ~70 K. Relative
      iron content variations in the tissue cells as well as small variations in the
      57Fe hyperfine parameters were demonstrated for healthy and patients' spleen and
      liver tissues on the base of measured Mossbauer spectra. The results obtained
      permit us to suggest small differences in the ferritin iron core structure in
      spleen and liver tissues from healthy donors and patients with hematological
      malignancies.

PMID- 30191453
TI  - Activities of daily living in older community-dwelling persons: a systematic
      review of psychometric properties of instruments.
AB  - BACKGROUND: Activities of daily living (ADL) are often used as predictors of
      health and function in older persons. This systematic review is part of a series
      initiated by the European Network for Action on Ageing and Physical Activity
      (EUNAAPA). AIM: To assess psychometric properties of ADL instruments for use in
      older populations. METHODS: Electronic databases (Medline, EMBASE, AMED,
      Psycinfo, CINAHL) were searched, using MeSH terms and relevant keywords. Studies,
      published in English, were included if they evaluated one or more psychometric
      properties of ADL instruments in community-dwelling older persons aged 60 years
      and older. Combination scales with IADL were excluded. This systematic review
      adhered to a pre-specified protocol regarding reliability, validity, and
      responsiveness. RESULTS: In total, 140 articles describing more than 50 different
      ADL instruments were included. Ten instruments which were applied in minimally
      three different articles of good quality (clear descriptions and adequate design
      according to the protocol), were evaluated for reliability, validity and
      responsiveness; each received a summary score. The four instruments with the
      highest scores were the Functional Autonomy Measurement System (SMAF), 5-items
      Katz list (although content and wording are often inconsistent across studies),
      Functional Independence and Difficulty Scale (FIDS) and the Barthel Index.
      DISCUSSION: Critical reflection is essential to avoid unnecessary modifications
      and use of instruments that have not been documented to be valid or reliable.
      CONCLUSION: Based on this systematic review, we recommend the SMAF, 5-item Katz,
      FIDS and Barthel index as ADL measures for research and care practice in older
      populations.

PMID- 30191454
TI  - Possible association between circulating CTRP3 and knee osteoarthritis in
      postmenopausal women.
AB  - BACKGROUND: Osteoarthritis (OA) is considered as one of the most common cause of
      chronic pain and functional disabilities in the elderly. AIM: To examine serum
      levels of complement-C1q TNF-related protein 3 (CTRP3) in postmenopausal women
      with knee OA. METHODS: A population-based cross-sectional study was performed in
      women who complained of chronic knee pain. All subjects were followed by clinical
      and weight-bearing bilateral anteroposterior radiographical examinations. The
      Kellgren and Lawrence (K&L) score was used for knee OA classification. Two groups
      of postmenopausal women were chosen to investigate CTRP3 as an OA marker who had
      the K&L score >= 3 as a case group and K&L <= 1 as a control group. Serum levels
      of CTRP3 were measured in two groups. RESULTS: According to K&L classification,
      36 subjects with knee OA and 54 age-matched without or mild OA were selected.
      After adjusting the obtained data for taking NSAID drugs, the concentration of Ln
      CTRP3 in serum of patients with OA was lower compared to control group [mean +/-
      SE, (0.39 +/- 0.05 ng/ml vs. 0.48 +/- 0.03 ng/ml, respectively, p = 0.04)].
      DISCUSSION: There is a possible role for CTRP3 as an anti-inflammatory mediator
      in knee OA in postmenopausal women. CONCLUSIONS: Our results indicate an
      association between CTRP3 and knee OA. However, a much more robust study is
      required to draw that circulating CTRP3 could be a clinical marker for
      osteoarthritis.

PMID- 30191455
TI  - Predictive model of length of stay in hospital among older patients.
AB  - BACKGROUND: Most National Health Service (NHS) hospital bed occupants are older
      patients because of their frequent admissions and prolonged length of stay (LOS).
      We evaluated demographic and clinical factors as predictors of LOS in a single
      NHS Trust and derived an equation to estimate LOS. METHODS: Stepwise logistic and
      linear regressions were used to predict prolonged LOS (upper-quintile LOS > 17
      days) and LOS respectively, from demographic factors and acute and pre-existing
      conditions. RESULTS: Of 374 (men:women = 127:247) admitted patients (20% to
      orthogeriatric, 69% to general medical and 11% to surgical wards), median age of
      85 years (IQR = 78-90), 77 had acute first hip fracture; 297 had previous hip
      fracture (median time since previous fracture = 2.4 years) and 21 (7.1%) had
      recurrent hip fracture, with median time since first fracture = 2.4 years. Median
      LOS was 6.5 days (IQR = 1.8-14.8), and 38 (10.2%) died after 4.8 days (IQR = 1.6
      14.3). Prolonged LOS was associated with discharge to places other than usual
      residence: OR = 3.1 (95% CI 1.7-5.7), acute stroke: OR = 10.1 (3.7-26.7), acute
      first hip fractures: OR = 6.8 (3.1-14.8), recurrent hip fractures: OR = 9.5 (3.2
      28.7), urinary tract infection/pneumonia: OR = 4.0 (2.1-8.0), other acute
      fractures: OR = 9.8 (3.0-32.3) and malignancy: OR = 15.0 (3.1-71.8). Predictive
      equation showed estimated LOS was 11.6 days for discharge to places other than
      usual residence, 15 days for pre-existing or acute stroke, 9-14 days for acute
      and recurrent hip fractures, infections, other acute fractures and malignancy;
      these factors together explained 32% of variability in LOS. CONCLUSIONS: A useful
      estimate of outcome and LOS can be made by constructing a predictive equation
      from information on hospital admission, to provide evidence-based guidance for
      resource requirements and discharge planning.

PMID- 30191456
TI  - Osteoporosis and vertebral fracture are associated with deterioration of
      activities of daily living and quality of life in patients with type 2 diabetes
      mellitus.
AB  - Patients with type 2 diabetes mellitus (T2DM) have an increased risk of fragility
      fracture. However, whether diabetes-related osteoporosis independently
      contributes to the deterioration of activities of daily living (ADLs) and quality
      of life (QOL) is unclear. This cross-sectional study investigated the association
      between osteoporosis, ADLs, and QOL in 309 patients with T2DM. ADLs and QOL were
      assessed using Barthel Index (BI) and a SF-36 questionnaire. Multiple logistic
      regression analyses adjusted for age, gender, T2DM duration, body mass index,
      hemoglobin A1c, estimated GFR, diabetic neuropathy, retinopathy, nephropathy,
      cardiovascular disease, cerebrovascular disease, peripheral artery disease, and
      anti-diabetic treatments were conducted. The number of patients with osteoporosis
      or vertebral fracture was 166 (53.7%) and 118 (38.2%), respectively. Osteoporosis
      was significantly associated with lower general health (GH), social functioning
      (SF), and role emotional (RE) (OR 2.56, 1.79, and 1.92, respectively; all p
      values < 0.05 at least) and marginally associated with lower BI (OR 2.39, p =
      0.068). Moreover, the presence of vertebral fracture grade 2 or 3 was
      significantly associated with lower BI, bodily pain (BP), GH, vitality, SF, and
      RE (OR 2.58, 2.01, 3.64, 1.99, 2.18, and 1.97, respectively; all p values < 0.05
      at least). Osteoporosis and severe vertebral fracture were associated with the
      deterioration of ADLs and QOL independently of other diabetic complications.
      Therefore, the management of diabetes-related osteoporosis is an important
      strategy to avoid the deterioration of ADLs and QOL in T2DM.

PMID- 30191457
TI  - Bone mineral density loss in ambulatory children with epilepsy in spite of using
      supplemental vitamin D in Southern Iran: a case-control study.
AB  - Epilepsy might have adverse effect on bone density due to underlying disease,
      drugs, vitamin D deficiency, immobilization and malnutrition. We investigated the
      bone mineral density in ambulatory vitamin-D supplemented children with epilepsy.
      This case-control study was conducted on 90 epileptic children aged 11.4 +/- 3.3
      years, and age and gender matched controls in pediatric neurology clinics of
      Shiraz, in Southern Iran, 2016. Anthropometric measurements, puberty, sun
      exposure, physical activity and biochemical variables were assessed. Bone mineral
      density was evaluated by dual-energy X-ray absorptiometry method. Data were
      analyzed by SPSS.v21. Prevalence of low bone mass in femur was more in patients
      (27%) than the controls (9%) (P value = 0.002). Age, weight Z score and height Z
      score were the most significant associated factors on lumbar BMD, BMAD, and femur
      BMD. Seizure duration and how it responded to anticonvulsants were the most
      associated factors with both lumbar and femur bone density. Sodium valproate and
      carbomazepin usage had negative association with lumbar Z score (beta = - 0.216,
      P = 0.017 and beta = - 0.336, P = 0.027, respectively). We hypothesized that
      epilepsy per se could affect bone density by an unknown pathophysiology, which
      was independent from vitamin D deficiency, effects of anticonvulsant and physical
      activity.

PMID- 30191458
TI  - The relationships between bone variables and physical fitness across the BMI
      spectrum in young adult women.
AB  - In this cross-sectional study we aimed to evaluate the relationship between
      physical fitness and bone variables across the body mass index (BMI) spectrum in
      women aged 20-35 years. The study included 13 underweight women (BMI < 18.5
      kg/m2), 24 normal weight women (BMI 18.5-24.9 kg/m2), and 20 overweight/obese
      women (BMI >= 25 kg/m2) aged between 20 and 35 years. Bone mineral density (BMD)
      and content (BMC) at the whole body, lumbar spine, and femoral neck, lumbar spine
      trabecular bone score, femoral neck geometry were assessed using dual-energy X
      ray absorptiometry. Cardiorespiratory fitness and lower limb muscle power were
      estimated using the 20-m shuttle run test and the Sargent jump test,
      respectively. The associations between bone variables and physical fitness were
      different according to BMI categories. Correlations between physical fitness and
      bone parameters are particularly significant in normal BMI and less significant
      in low and high BMI. Multivariate ANCOVA regression models demonstrated that
      absolute VO2max (L/min) is a strong determinant of all the bone parameters
      regardless of BMI. Implementing strategies for increasing VO2max (L/min) by
      increasing lean mass and promoting resistance and/or high-intensity interval
      training could be effective to optimize bone health in underweight and overweight
      young adult women.

PMID- 30191459
TI  - Brain-Derived Glia Maturation Factor beta Participates in Lung Injury Induced by
      Acute Cerebral Ischemia by Increasing ROS in Endothelial Cells.
AB  - Brain damage can cause lung injury. To explore the mechanism underlying the lung
      injury induced by acute cerebral ischemia (ACI), we established a middle cerebral
      artery occlusion (MCAO) model in male Sprague-Dawley rats. We focused on glia
      maturation factor beta (GMFB) based on quantitative analysis of the global rat
      serum proteome. Polymerase chain reaction, western blotting, and
      immunofluorescence revealed that GMFB was over-expressed in astrocytes in the
      brains of rats subjected to MCAO. We cultured rat primary astrocytes and
      confirmed that GMFB was also up-regulated in primary astrocytes after oxygen
      glucose deprivation (OGD). We subjected the primary astrocytes to Gmfb RNA
      interference before OGD and collected the conditioned medium (CM) after OGD. We
      then used the CM to culture pulmonary microvascular endothelial cells (PMVECs)
      acquired in advance and assessed their status. The viability of the PMVECs
      improved significantly when Gmfb was blocked. Moreover, ELISA assays revealed an
      elevation in GMFB concentration in the medium after OGD. Cell cultures containing
      recombinant GMFB showed increased levels of reactive oxygen species and a
      deterioration in the state of the cells. In conclusion, GMFB is up-regulated in
      astrocytes after ACI, and brain-derived GMFB damages PMVECs by increasing
      reactive oxygen species. GMFB might thus be an initiator of the lung injury
      induced by ACI.

PMID- 30191460
TI  - CYP2D6 allele frequencies in Korean population, comparison with East Asian,
      Caucasian and African populations, and the comparison of metabolic activity of
      CYP2D6 genotypes.
AB  - Cytochrome P450 (CYP) 2D6 is present in less than about 2% of all CYP enzymes in
      the liver, but it is involved in the metabolism of about 25% of currently used
      drugs. CYP2D6 is the most polymorphic among the CYP enzymes. We determined
      alleles and genotypes of CYP2D6 in 3417 Koreans, compared the frequencies of
      CYP2D6 alleles with other populations, and observed the differences in
      pharmacokinetics of metoprolol, a prototype CYP2D6 substrate, depending on CYP2D6
      genotype. A total of 3417 unrelated healthy subjects were recruited for the
      genotyping of CYP2D6 gene. Among them, 42 subjects with different CYP2D6
      genotypes were enrolled in the pharmacokinetic study of metoprolol. The
      functional allele *1 and *2 were present in frequencies of 34.6 and 11.8%,
      respectively. In decreased functional alleles, *10 was the most frequent with
      46.2% and *41 allele was present in 1.4%. The nonfunctional alleles *5 and *14
      were present at 4.5 and 0.5% frequency, respectively. The *X * N allele was
      present at a frequency of 1.0%. CYP2D6*1/*1, *1/*2 and *2/*2 genotypes with
      normal enzyme activity were present in 12.1%, 8.6% and 1.4% of the subjects,
      respectively. CYP2D6*5/*5, *5/*14, and *14/*14 genotypes classified as poor
      metabolizer were only present in 4, 2, and 1 subjects, respectively. Mutant
      genotypes with frequencies of more than 1% were CYP2D6*1/*10 (32.0%), *10/*10
      (22.3%), *2/*10 (11.7%), *5/*10 (3.7%), *1/*5 (2.5%), and *10/*41 (1.2%). The
      relative clearance of metoprolol in CYP2D6*1/*10, *1/*5, *10/*10, *5/*10, and
      *5/*5 genotypes were 69%, 57%, 24%, 14% and 9% of CYP2D6*wt/*wt genotype,
      respectively. These results will be very useful in establishing a strategy for
      precision medicine related to the genetic polymorphism of CYP2D6.

PMID- 30191461
TI  - Canadian mining and ill health in Latin America: a call to action.
AB  - This commentary argues that Canada's public and global health communities have a
      special ethical and political responsibility to act to reverse the harms
      associated with Canadian mining activities in Latin America and beyond through
      advocacy, research, and using their public voice. We begin with an overview of
      the direct and indirect health effects of mining, drawing especially on Latin
      America where 50-70% of mining activity involves Canadian companies. Then we
      examine the judicial, legislative, financial, and diplomatic contexts that make
      Canada such a welcome host and champion of the mining sector. Finally, we turn to
      the responsibility of the public and global health communities, offering concrete
      recommendations for using research, practical expertise public health solidarity
      networks, and political clout to speak out and advocate for policies that redress
      the harms caused by mining.

PMID- 30191462
TI  - Interprovincial variation in pre-pregnancy body mass index and gestational weight
      gain and their impact on neonatal birth weight with respect to small and large
      for gestational age.
AB  - OBJECTIVES: To explore provincial variation in both excess and inadequate pre
      pregnancy body mass index (BMI) and gestational weight gain (GWG) and their
      impact on small- and large-for-gestational-age (SGA, LGA) infants. METHODS: Four
      provinces with a perinatal database capturing the required exposures
      participated: British Columbia (BC), Ontario (ON), Nova Scotia (NS), and
      Newfoundland and Labrador (NL). In multiple, concurrent retrospective studies, we
      included women >= 19 years, who gave birth from 22+0 to 42+6 weeks' gestation, to
      a live singleton from April 2013-March 2014. From adjusted odds ratios, we
      calculated population attributable fractions (PAF) of SGA and LGA for BMI and
      GWG. RESULTS: The proportion of overweight and obese women increased from western
      to eastern Canada. In BC, ON, NS, and NL, the proportions of women who were
      overweight were 21.1%, 24.0%, 23.7%, and 25.4%, while obesity proportions were
      14.2%, 18.1%, 24.2%, and 29.8%, respectively. Excess GWG affected 53.9%, 49.9%,
      57.6%, and 65.6% of women, respectively. Excess GWG contributed to 29.5-42.5% of
      LGA, compared with the PAFs for overweight (6.8-12.0%) and obesity (13.2-20.6%).
      Inadequate GWG's contribution to SGA (4.8-12.3%) was higher than underweight
      BMI's (2.9-6.2%). CONCLUSION: In this interprovincial study, high and increasing
      proportions of women from west to east had excess pre-pregnancy BMI, and between
      half to two thirds had excess GWG. The contributions of GWG outside of
      recommendations to SGA and LGA were greater than that of low or high BMI. GWG is
      a potentially modifiable determinant of SGA and LGA across Canada.

PMID- 30191463
TI  - Treatment Duration, Healthcare Resource Utilization, and Costs Among Chemotherapy
      Naive Patients with Metastatic Castration-Resistant Prostate Cancer Treated with
      Enzalutamide or Abiraterone Acetate: A Retrospective Claims Analysis.
AB  - INTRODUCTION: Enzalutamide and abiraterone acetate (plus prednisone) are new
      hormonal treatments for metastatic castration-resistant prostate cancer (mCRPC).
      This study compared treatment duration, healthcare resource utilization (HRU),
      and treatment costs for chemotherapy-naive mCRPC patients treated with
      enzalutamide or abiraterone acetate in the USA. METHODS: Chemotherapy-naive mCRPC
      patients initiating treatment with enzalutamide or abiraterone acetate were
      identified from administrative claims. Continuous enrollment >= 6 months before
      and >= 3 months after the index date (initiation date of enzalutamide or
      abiraterone acetate) was required. Treatment duration, all-cause and prostate
      cancer-related HRU, and costs were estimated during the post-index period.
      Multivariable analyses compared HRU and costs between cohorts, adjusting for
      baseline characteristics. RESULTS: Overall, 920 chemotherapy-naive patients
      initiated enzalutamide and 2310 initiated abiraterone acetate (median follow-up,
      10.7 and 13.5 months, respectively). More enzalutamide-treated patients had
      corticosteroid-sensitive comorbidities at baseline. Treatment duration was longer
      with enzalutamide versus abiraterone acetate (median, 10.7 vs. 8.8 months; P =
      0.008). Enzalutamide was associated with fewer all-cause inpatient admissions
      [adjusted incidence rate ratio (95% confidence interval) 0.87 (0.76, 0.99)], days
      of hospitalization [0.84 (0.70, 1.02)], and outpatient visits [0.94 (0.90,
      0.98)], and fewer prostate cancer-related outpatient visits [0.92 (0.87, 0.96)]
      compared with abiraterone acetate. Enzalutamide was also associated with lower
      prostate cancer-related inpatient and emergency department costs [adjusted
      differences, $122 (P = 0.024) and $28 (P = 0.009), respectively]. CONCLUSION:
      Chemotherapy-naive mCRPC patients treated with enzalutamide versus abiraterone
      acetate had longer treatment duration and incurred lower HRU and prostate cancer
      related inpatient and emergency department costs. FUNDING: Astellas Pharma Inc.

PMID- 30191464
TI  - Preventing Clinically Important Deterioration of COPD with Addition of
      Umeclidinium to Inhaled Corticosteroid/Long-Acting beta2-Agonist Therapy: An
      Integrated Post Hoc Analysis.
AB  - INTRODUCTION: Assessing clinically important measures of disease progression is
      essential for evaluating therapeutic effects on disease stability in chronic
      obstructive pulmonary disease (COPD). This analysis assessed whether providing
      additional bronchodilation with the long-acting muscarinic antagonist
      umeclidinium (UMEC) to patients treated with inhaled corticosteroid (ICS)/long
      acting beta2-agonist (LABA) therapy would improve disease stability compared with
      ICS/LABA therapy alone. METHODS: This integrated post hoc analysis of four 12
      week, randomized, double-blind trials (NCT01772134, NCT01772147, NCT01957163,
      NCT02119286) compared UMEC 62.5 ug with placebo added to open-label ICS/LABA in
      symptomatic patients with COPD (modified Medical Research Council dyspnea scale
      score >= 2). A clinically important deterioration (CID) was defined as: a
      decrease from baseline of >= 100 mL in trough forced expiratory volume in 1 s
      (FEV1), an increase from baseline of >= 4 units in St George's Respiratory
      Questionnaire (SGRQ) total score, or a moderate/severe exacerbation. Risk of a
      first CID was evaluated in the intent-to-treat (ITT) population and in patients
      stratified by Global initiative for chronic Obstructive Lung Disease (GOLD)
      classification, exacerbation history and type of ICS/LABA therapy. Adverse events
      (AEs) were also assessed. RESULTS: Overall, 1637 patients included in the ITT
      population received UMEC + ICS/LABA (n = 819) or placebo + ICS/LABA (n = 818).
      Additional bronchodilation with UMEC reduced the risk of a first CID by 45-58% in
      the ITT population and all subgroups analyzed compared with placebo (all p <
      0.001). Improvements were observed in reducing FEV1 (69% risk reduction; p <
      0.001) and exacerbation (47% risk reduction; p = 0.004) events in the ITT
      population. No significant reduction in risk of a SGRQ CID was observed. AE
      incidence was similar between treatment groups. CONCLUSION: Symptomatic patients
      with COPD receiving ICS/LABA experience frequent deteriorations. Additional
      bronchodilation with UMEC significantly reduced the risk of CID and provided
      greater short-term stability versus continued ICS/LABA therapy in these patients.
      FUNDING: GlaxoSmithKline (study number: 202067). Plain language summary available
      for this article.

PMID- 30191466
TI  - Overexpression of StGA2ox1 Gene Increases the Tolerance to Abiotic Stress in
      Transgenic Potato (Solanum tuberosum L.) Plants.
AB  - It has been known that GA2ox is one kind of key enzyme gene in the gibberellin
      synthesis pathway, which plays important regulatory roles throughout plant whole
      growth and development. In this article, one of the GA2ox family genes,
      designated StGA2ox1, was isolated from potato (Solanum tuberosum L.). The full
      length of cDNA is 1005 bp, and the cDNA corresponds to a protein of 334 amino
      acids; this protein was classified in a group with NtGA2ox3 based on multiple
      sequence alignments and phylogenetic characterization. A plant expression vector
      pCAEZ1383-StGA2ox1 was established. qRT-PCR showed that the expression of RD28,
      DREB1, WRKY1, and SnRK2 genes in StGA2ox1 transgenic plant is higher than that in
      non-transformed control under dehydration, low temperature conditions, and
      abscisic acid treatments. Overexpression of StGA2ox1 cDNA in transgenic potato
      plants exhibited an improved salt, drought, exogenous hormone, and low
      temperature stress tolerance in comparison to the non-transformed plant. The
      enhanced stress tolerance may be associated with the subsequent accumulation of
      proline osmoprotectant in addition to a better control of chlorophyll,
      carotenoids, and water loss. These data suggest that the StGA2ox1 is involved in
      the regulation of plant growth and tolerance in potato by regulating the
      synthesis of gibberellin.

PMID- 30191465
TI  - Real-world Management of Women with Postmenopausal Osteoporosis Treated with
      Denosumab: A Prospective Observational Study in the Czech Republic and Slovakia.
AB  - INTRODUCTION: Osteoporosis is characterized by low bone mineral density (BMD) and
      an increased risk of fracture. In randomized controlled trials, denosumab has
      been shown to significantly reduce the fracture risk in women with osteoporosis.
      However, little is known about the real-world management of women who are
      prescribed denosumab. METHODS: This multicenter, prospective, observational real
      world study in the Czech Republic and Slovakia evaluated the baseline
      characteristics and clinical management of women with postmenopausal osteoporosis
      prescribed denosumab for 24 months. RESULTS: A total of 600 women were included
      (300 in each country). In the Czech Republic and Slovakia, respectively, mean age
      at enrollment was 69.0 and 64.3 years, 67.7% and 30.0% of patients had a previous
      osteoporotic fracture, and 85.0% and 48.7% had previously received osteoporosis
      medication. In both countries, 'low BMD T score' and 'a history of osteoporotic
      fracture' were the main reasons for prescribing denosumab. Most patients received
      all four post-baseline denosumab injections (Czech Republic, 82.0%; Slovakia,
      81.0%), and more than 98% of patients in both countries received all injections
      at the prescribing center. At 24 months, most patients experienced an increase in
      BMD T score for the lumbar spine, total hip, or femoral neck (Czech Republic,
      69.7-91.7%; Slovakia, 67.1-92.9%). Adverse drug reactions were consistent with
      the known safety profile of denosumab. CONCLUSION: Baseline characteristics of
      patients receiving denosumab in the Czech Republic and Slovakia reflect the
      reimbursement criteria for this agent in each country. The findings of our study
      in patients who are at high risk for fracture are consistent with the growing
      body of evidence demonstrating the effectiveness of denosumab in real-world
      clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov identifier,
      NCT01652690. FUNDING: Amgen Inc.

PMID- 30191467
TI  - Parental Investments in College and Later Cash Transfers.
AB  - Parents often provide generous financial transfers to their adult children,
      perhaps assisting with college expenses, recognizing major life course events, or
      cushioning against negative financial shocks. Because resources are limited, a
      transfer made to one child likely affects transfers made to others in the family.
      Despite such possibilities, data limitations have led previous authors to focus
      almost exclusively on a single type of transfer made at a single point in time.
      Using data from the Health and Retirement Study, we examine the relationships
      among parental transfers for college and later cash transfers to all children
      within a family. We find that parents typically spend differentially on the
      postsecondary schooling of their children but find no evidence that this
      differential spending is offset by later cash transfers.

PMID- 30191468
TI  - Inhibition of Neointima Hyperplasia, Inflammation, and Reactive Oxygen Species in
      Balloon-Injured Arteries by HVJ Envelope Vector-Mediated Delivery of Superoxide
      Dismutase Gene.
AB  - Extracellular superoxide dismutase (EC-SOD) has been implicated in regulation of
      vascular function but its underlying molecular mechanism is largely unknown.
      These two-step experiments investigate whether hemagglutinating virus of Japan
      envelope (HVJ-E) vector-mediated EC-SOD gene delivery might protect against
      neointima formation, vascular inflammation, and reactive oxygen species (ROS)
      generation, and also explore cell growth signaling pathways. The first in-vitro
      experiment was performed to assess the transfection efficacy and safety of HVJ-E
      compared to lipofectamine(r). Results revealed that HVJ-E has higher transfection
      efficiency and lower cytotoxicity than those of lipofectamine(r). Another in-vivo
      study initially used balloon denudation to rat carotid artery, then delivered EC
      SOD cDNA through the vector of HVJ-E. Arterial section with H&E staining from the
      animals 14 days after balloon injury showed a significant reduction of intima-to
      media area ratio in EC-SOD transfected arteries when compared with control (empty
      vector-transfected arteries) (p < 0.05). Arterial tissue with EC-SOD gene
      delivery also exhibited lower levels of ROS, as assessed by fluorescent
      microphotography with dihydroethidium staining. Quantitative RT-PCR revealed that
      EC-SOD gene delivery significantly diminished mRNA expression of tumor necrosis
      factor (TNF)-alpha and interleukin (IL)-1beta (p < 0.05 in all comparisons). An
      immunoblotting assay from vascular smooth muscle cell (VSMC) cultures showed that
      the EC-SOD transfected group attenuated the activation of MEK1/2, ERK1/2, and Akt
      signaling significantly. In conclusion, EC-SOD overexpression by HVJ-E vector
      inhibits neointima hyperplasia, inflammation, and ROS level triggered by balloon
      injury. The modulation of cell growth-signaling pathways by EC-SOD in VSMCs might
      play an important role in these inhibitory effects.

PMID- 30191469
TI  - Risk of Hospitalization for Cardiovascular Events with beta-Blockers in
      Hypertensive Patients: A Retrospective Cohort Study.
AB  - INTRODUCTION: beta-Blockers are a heterogenous class of drugs that are no longer
      recommended for initial antihypertension monotherapy due to unfavorable long-term
      cardiovascular events observed with non-vasodilatory beta-blockers. However, the
      comparative cardiovascular event risk between the vasodilatory beta1-selective
      antagonist/beta3 agonist nebivolol and non-vasodilatory beta1-blockers, atenolol
      and metoprolol, is unknown. METHODS: Incident nebivolol, atenolol, or metoprolol
      monotherapy users with hypertension were identified using US claims data (2007
      2014). The first beta-blocker claim on/after 1/1/2008 defined the index
      drug/date. Hypertensive patients without pre-index cardiovascular history were
      followed until index drug discontinuation (> 90 day supply gap), use of other
      beta-blockers, or end of continuous plan enrollment. Patients were pair-wise
      propensity score-matched using logistic regression, adjusted for baseline
      demographics, Charlson Comorbidity Index score, comorbid chronic pulmonary
      disease, rheumatic disease, renal disease, and diabetes, and use of other
      antihypertensive drugs during baseline. Time to first hospital claim for a
      cardiovascular event was assessed via Cox proportional hazards regression,
      adjusted for the variables above. RESULTS: Inclusion criteria were met by 81,402
      patients (n = 27,134 in each matched treatment cohort), with no between-cohort
      differences in baseline characteristics, comorbid conditions, or average follow
      up duration. Atenolol and metoprolol cohorts had greater risk of hospitalization
      for a composite event (myocardial infarction, angina, congestive heart failure,
      stroke) than nebivolol users (adjusted hazard ratios [95% confidence interval]
      atenolol: 1.68 [1.29, 2.17]; metoprolol: 2.05 [1.59, 2.63]; P < 0.001, both).
      Risks of most individual cardiovascular events were also lower with nebivolol,
      including myocardial infarction and angina versus atenolol, and myocardial
      infarction, congestive heart failure, and angina versus metoprolol (P < 0.05,
      all). CONCLUSIONS: Nebivolol was associated with significantly lower risk of
      hospitalization due to composite cardiovascular events than atenolol or
      metoprolol in this large retrospective cohort study of monotherapy with three
      different beta1-selective blockers in hypertensive patients. FUNDING: Allergan
      plc, Madison, NJ, USA.

PMID- 30191471
TI  - Issues in Reproducible Simulation Research.
AB  - In recent years, serious concerns have arisen about reproducibility in science.
      Estimates of the cost of irreproducible preclinical studies range from 28 billion
      USD per year in the USA alone (Freedman et al. in PLoS Biol 13(6):e1002165, 2015)
      to over 200 billion USD per year worldwide (Chalmers and Glasziou in Lancet
      374:86-89, 2009). The situation in the social sciences is not very different:
      Reproducibility in psychological research, for example, has been estimated to be
      below 50% as well (Open Science Collaboration in Science 349:6251, 2015). Less
      well studied is the issue of reproducibility of simulation research. A few
      replication studies of agent-based models, however, suggest the problem for
      computational modeling may be more severe than for laboratory experiments
      (Willensky and Rand in JASSS 10(4):2, 2007; Donkin et al. in Environ Model Softw
      92:142-151, 2017; Bajracharya and Duboz in: Proceedings of the symposium on
      theory of modeling and simulation-DEVS integrative M&S symposium, pp 6-11, 2013).
      In this perspective, we discuss problems of reproducibility in agent-based
      simulations of life and social science problems, drawing on best practices
      research in computer science and in wet-lab experiment design and execution to
      suggest some ways to improve simulation research practice.

PMID- 30191470
TI  - Social feedback interferes with implicit rule learning: Evidence from event
      related brain potentials.
AB  - The human brain can learn contingencies built into stimulus sequences
      unconsciously. The quality of such implicit learning has been connected to
      stimulus social relevance, but results so far are inconsistent. We engaged
      participants in an implicit-intentional learning task in which they learned to
      discriminate between legal and illegal card triads on the sole basis of feedback
      provided within a staircase procedure. Half of the participants received feedback
      from pictures of faces with a happy or sad expression (social group) and the
      other half based on traffic light icons (symbolic group). We hypothesised that
      feedback from faces would have a greater impact on learning than that from
      traffic lights. Although performance during learning did not differ between
      groups, the feedback error-related negativity (fERN) was delayed by ~20 ms for
      social relative to symbolic feedback, and the P3b modulation elicited by
      infrequent legal card triads within a stream of illegal ones during the test
      phase was significantly larger in the symbolic than the social feedback group.
      Furthermore, the P3b mean amplitude recorded at test negatively correlated with
      the latency of the fERN recorded during learning. These results
      counterintuitively suggest that, relative to symbolic feedback, socially salient
      feedback interferes with implicit learning.

PMID- 30191472
TI  - Reproducible Research Using Biomodels.
AB  - Like other types of computational research, modeling and simulation of biological
      processes (biomodels) is still largely communicated without sufficient detail to
      allow independent reproduction of results. But reproducibility in this area of
      research could easily be achieved by making use of existing resources, such as
      supplying models in standard formats and depositing code, models, and results in
      public repositories.

PMID- 30191474
TI  - The efficacy of HRAS and CDK4/6 inhibitors in anaplastic thyroid cancer cell
      lines.
AB  - PURPOSE: Anaplastic thyroid carcinomas (ATCs) are non-responsive to multimodal
      therapy, representing one of the major challenges in thyroid cancer. Previously,
      our group has shown that genes involved in cell cycle are deregulated in ATCs,
      and the most common mutations in these tumours occurred in cell proliferation and
      cell cycle related genes, namely TP53, RAS, CDKN2A and CDKN2B, making these genes
      potential targets for ATCs treatment. Here, we investigated the inhibition of
      HRAS by tipifarnib (TIP) and cyclin D-cyclin-dependent kinase 4/6 (CDK4/6) by
      palbociclib (PD), in ATC cells. METHODS: ATC cell lines, mutated or wild type for
      HRAS, CDKN2A and CDKN2B genes, were used and the cytotoxic effects of PD and TIP
      in each cell line were evaluated. Half maximal inhibitory concentration (IC50)
      values were determined for these drugs and its effects on cell cycle, cell death
      and cell proliferation were subsequently analysed. RESULTS: Cell culture studies
      demonstrated that 0.1 uM TIP induced cell cycle arrest in the G2/M phase (50%, p
      < 0.01), cell death, and inhibition of cell viability (p < 0.001), only in the
      HRAS mutated cell line. PD lowest concentration (0.1 uM) increased significantly
      cell cycle arrest in the G0/G1 phase (80%, p < 0.05), but only in ATC cell lines
      with alterations in CDKN2A/CDKN2B genes; additionally, 0.5 uM PD induced cell
      death. The inhibition of cell viability by PD was more pronounced in cells with
      alterations in CDKN2A/CDKN2B genes (p < 0.05) and/or cyclin D1 overexpression.
      CONCLUSIONS: This study suggests that TIP and PD, which are currently in clinical
      trials for other types of cancer, may play a relevant role in ATC treatment,
      depending on the specific tumour molecular profile.

PMID- 30191475
TI  - Gradual formation of visual working memory representations of motion directions.
AB  - Although it is well accepted that the formation of visual working memory (VWM)
      representations from simple static features is a rapid and effortless process
      that completes within several hundred milliseconds, the storage of motion
      information in VWM within that time scale can be challenging due to the limited
      processing capacity of the visual system. Memory formation can also be demanding
      especially when motion stimuli are visually complex. Here, we investigated
      whether the formation of VWM representations of motion direction is more gradual
      than that of static orientation and examined the effects of stimulus complexity
      on that process. To address these issues, we examined how the number and the
      precision of stored items in VWM develop over time by using a continuous report
      procedure. Results showed that while a viewing duration of several seconds was
      required for the successful storage of multiple motion directions in VWM
      regardless of motion complexity, the accumulation of memory precision was much
      slower when the motion stimulus was visually complex (Experiments 1 & 2).
      Additional experiments showed that the difference in memory performance for
      simple and complex motion stimuli cannot be explained by differences in signal-to
      noise levels of the stimulus (Experiment 3). These results demonstrate remarkable
      temporal limitations in the formation of VWM representations for dynamic objects,
      and further show how this process is affected by stimulus properties such as
      visual complexity and signal-to-noise levels.

PMID- 30191473
TI  - Public Health Agency Responses and Opportunities to Protect Against Health
      Impacts of Climate Change Among US Populations with Multiple Vulnerabilities.
AB  - During the past several decades, unprecedented global changes in climate have
      given rise to an increase in extreme weather and other climate events and their
      consequences such as heavy rainfall, hurricanes, flooding, heat waves, wildfires,
      and air pollution. These climate effects have direct impacts on human health such
      as premature death, injuries, exacerbation of health conditions, disruption of
      mental well-being, as well as indirect impacts through food- and water-related
      infections and illnesses. While all populations are at risk for these adverse
      health outcomes, some populations are at greater risk because of multiple
      vulnerabilities resulting from increased exposure to risk-prone areas, increased
      sensitivity due to underlying health conditions, and limited adaptive capacity
      primarily because of a lack of economic resources to respond adequately. We
      discuss current governmental public health responses and their future
      opportunities to improve resilience of special populations at greatest risk for
      adverse health outcomes. Vulnerability assessment, adaptation plans, public
      health emergency response, and public health agency accreditation are all current
      governmental public health actions. Governmental public health opportunities
      include integration of these current responses with health equity initiatives and
      programs in communities.

PMID- 30191476
TI  - Mid-level feature contributions to category-specific gaze guidance.
AB  - Our research has previously shown that scene categories can be predicted from
      observers' eye movements when they view photographs of real-world scenes. The
      time course of category predictions reveals the differential influences of bottom
      up and top-down information. Here we used these known differences to determine to
      what extent image features at different representational levels contribute toward
      guiding gaze in a category-specific manner. Participants viewed grayscale
      photographs and line drawings of real-world scenes while their gaze was tracked.
      Scene categories could be predicted from fixation density at all times over a 2-s
      time course in both photographs and line drawings. We replicated the shape of the
      prediction curve found previously, with an initial steep decrease in prediction
      accuracy from 300 to 500 ms, representing the contribution of bottom-up
      information, followed by a steady increase, representing top-down knowledge of
      category-specific information. We then computed the low-level features (luminance
      contrasts and orientation statistics), mid-level features (local symmetry and
      contour junctions), and Deep Gaze II output from the images, and used that
      information as a reference in our category predictions in order to assess their
      respective contributions to category-specific guidance of gaze. We observed that,
      as expected, low-level salience contributes mostly to the initial bottom-up peak
      of gaze guidance. Conversely, the mid-level features that describe scene
      structure (i.e., local symmetry and junctions) split their contributions between
      bottom-up and top-down attentional guidance, with symmetry contributing to both
      bottom-up and top-down guidance, while junctions play a more prominent role in
      the top-down guidance of gaze.

PMID- 30191477
TI  - Competition between color and luminance in motion correspondence.
AB  - The visual system needs to solve the correspondence problem (i.e., which elements
      belong together across space and time) to allow stable representations of
      objects. It has been shown that spatiotemporal and feature information can
      influence this correspondence process, but it is unclear how these factors
      interact with each other, especially when they are more or less prominent due to
      changes in contrast magnitude. We investigated this question using a variation of
      the Ternus display, an ambiguous apparent motion display, in which three elements
      can either be perceived as moving together (group motion) or as one element
      jumping across the others (element motion). In the first experiment, we biased
      the percept by presenting some of the elements with the same feature (isoluminant
      color or luminance), such that they were either compatible with group motion or
      with element motion (simple feature biases). To change the strength of the
      feature bias, we manipulated the contrast magnitude of the feature. In three more
      experiments we introduced competitive displays, in which some of the elements
      showed a color/luminance based element bias of varying contrast magnitude, while
      other elements showed a luminance/color based group bias of varying contrast
      magnitude (competing feature bias). We found that for a simple feature bias the
      contrast magnitude did not affect the strength of the bias. For competing feature
      biases, however, the contrast magnitude did influence correspondence, as the bias
      strength increased with contrast. The implications of our results for current
      motion and feature-based theories of correspondence are discussed.

PMID- 30191478
TI  - Correction to: Tension band wiring for simple olecranon fractures: evaluation of
      surgical technique.
AB  - Unfortunately, after publication of this article [1], it was noticed that the
      author J. Carel Goslings was tagged incorrectly during the production process.
      This resulted in the PubMed display of the author name as 'J Carel Goslings'. The
      correct display is 'Goslings JC'. This correction contains the correct tagging.

PMID- 30191479
TI  - Enhanced Photovoltaic Properties in Sb2S3 Planar Heterojunction Solar Cell with a
      Fast Selenylation Approach.
AB  - Poor thermostability of Sb2S3 in vacuum hinders the possibility of achieving high
      quality crystalline films. In order to enhance the photovoltaic properties of
      Sb2S3 planar heterojunction solar cells, a selenylation-based post-treatment
      approach has been employed. Selenylation performed over 15 min on the Sb2S3 film
      resulted in an enhancement in the conversion efficiency from ~ 0.01 to 2.20%.
      Effect of the selenylation on the evolution of morphology, crystal structure,
      composition distributions, and photovoltaic behavior has been investigated. The
      variation in the energy levels of Sb2S3/CdS junction has been also been
      discussed. Results show that selenylation not only enhanced the crystallinity of
      Sb2S3 film but also provided a suitable energy level which facilitated charge
      transport from absorber to the buffer layer.

PMID- 30191480
TI  - The mitochondrial Nod-like receptor NLRX1 modifies apoptosis through SARM1.
AB  - NLRX1, the mitochondrial NOD-like receptor (NLR), modulates apoptosis in response
      to both intrinsic and extrinsic cues. Insights into the mechanism of how NLRX1
      influences apoptosis remain to be determined. Here, we demonstrate that NLRX1
      associates with SARM1, a protein with a toll/interleukin-1 receptor (TIR)
      containing domain also found in adaptor proteins downstream of toll-like
      receptors, such as MyD88. While a direct role of SARM1 in innate immunity is
      unclear, the protein plays essential roles in Wallerian degeneration (WD), a type
      of neuronal catabolism occurring following axonal severing or damage. In non
      neuronal cells, we found that endogenous SARM1 was equally distributed in the
      cytosol and the mitochondrial matrix, where association with NLRX1 occurred. In
      these cells, the apoptotic role of NLRX1 was fully dependent on SARM1, indicating
      that SARM1 was downstream of NLRX1 in apoptosis regulation. In primary murine
      neurons, however, Wallerian degeneration induced by vinblastine or NGF
      deprivation occurred in SARM1- yet NLRX1-independent manner, suggesting that WD
      requires the cytosolic pool of SARM1 or that NLRX1 levels in neurons are too low
      to contribute to WD regulation. Together, these results shed new light into the
      mechanisms through which NLRX1 controls apoptosis and provides evidence of a new
      link between NLR and TIR-containing proteins.

PMID- 30191481
TI  - Lasalocid immediately and completely prevents the myocardial damage caused by
      coronary ischemia reperfusion in rat heart.
AB  - Lasalocid, a specific mobile membrane ionophore for calcium, dopamine and
      norepinephrine was assayed in its capacity to reduce or maintain unaltered the
      cardiovascular function in conditions of imminent myocardial injury. In
      experiments of coronary blockade and reperfusion carried out in rat heart, it was
      found that when administered from 5 to 30 minutes prior to the induction of
      coronary blockade, at a concentration of 2 mg/kg of body weight, the ionophore
      immediately, simultaneously, and completely interrupts the blood pressure decay,
      cardiac frequency increase, electrical ventricular tachycardia and fibrillation,
      as well as the fall of mitochondrial oxidative phosphorylation and decay of
      mitochondrial oxygen uptake provoked by the induced myocardial injury. It appears
      that the molecular mode of action of the lasalocid is associated with its unique
      ability to transport both calcium and the catecholamines, dopamine and
      norepinephrine, across mitochondrial and bimolecular lipid membranes, as well as
      through synaptic cell membrane terminals from rat heart, myocardial fibers of the
      heart and heart chromaffin membrane vesicles. It is suggested that for the
      potential medical use of lasalocid to detain incoming ischemic myocardial damage,
      there exists a need to develop a personal electronic device able to
      simultaneously monitor, detect, and inform on the very early and simultaneous
      signs of cardiac alterations of electrical, mechano-chemical, metabolic and
      hydraulic nature, all which precede heart failure and to administer the
      lasalocid.

PMID- 30191482
TI  - Non-coding RNA Resources.
AB  - Non-coding RNAs (ncRNAs) are a kind of functional RNA molecules that are not
      translated into proteins. There is now a large number of evidence suggests that
      ncRNAs are associated with various disease processes including cancer. Follow the
      rapid development of next-generation sequencing (NGS) technologies, a large
      amount of ncRNAs has accumulated in a short period of time. To date, many ncRNA
      related databases have already been developed. Here we systematically reviewed
      these specialized ncRNA-related databases, and we expect these databases could
      serve as useful resources for researchers to further investigate and explore the
      associations between ncRNAs and human diseases.

PMID- 30191483
TI  - Systematic Identification of Non-coding RNAs.
AB  - Non-coding RNAs (ncRNAs) are biologically significant in variable ways. They
      modulate gene expression at the levels of transcription and post-transcription.
      MiRNAs and lncRNAs are two major classes of non-coding RNAs and have been
      extensively characterized. They are implicated in various biological processes
      and diseases. Thus, identification of miRNAs and lncRNAs are fundamental to
      further understand their roles and dissect their mechanisms. Here, we overviewed
      pipelines of identifying miRNAs and lncRNAs based on next-generation sequencing
      technologies. We applied the pipelines to identify miRNAs in multiple cell lines
      and perform expression quantification of mature, precursor and primary miRNAs. In
      addition, we provided an alternative way to re-annotate lncRNAs from microarray
      data. We summarized multiple resources and databases for lncRNA annotation and
      compared their annotation processes and specific parameters. Finally, we utilized
      RNA-seq and miRNA-seq data to construct a comprehensive transcriptome containing
      miRNAs, lncRNAs and protein-coding genes in heart failure.

PMID- 30191484
TI  - Functional Characterization of Non-coding RNAs Through Genomic Data Fusion.
AB  - Acting as a class of regulators of gene expression, miRNAs play crucial roles in
      various biological processes, such as cell proliferation, differentiation, and
      apoptosis. Increasing evidence indicates that dysregulation of miRNA expression
      and function is related to the pathogenesis of many human diseases. Here, we
      applied an integration strategy to identify conserved miRNA co-expression
      relationships and constructed a miRNA co-expression network based on human and
      mouse miRNA expression data. We performed large-scale bioinformatics analyses of
      conserved miRNA co-expression relationships and their functional links and
      confirmed that these conserved co-expressed miRNA relationships in the network
      tend to be functionally relevant. Co-expressed miRNA pairs regulated by common
      TFs are significantly enriched within the same miRNA clusters and/or miRNA
      families. Mapping well-known disease miRNAs to the network, we identified three
      miRNA sub-networks that are highly related to cancer risk. Furthermore, we
      observed that these conserved co-expressed miRNA sub-networks cooperatively
      regulate cancer-related functions through synergistically repressing crucial
      components of these processes. Our results suggest that co-expressed miRNAs
      assist to drive the initiation and progression of cancer in a cooperative manner.

PMID- 30191485
TI  - Genomic-Scale Prioritization of Disease-Related Non-coding RNAs.
AB  - The recent explosion in the number and diversity of non-coding RNAs (ncRNAs)
      identified by the large-scale technologies brings new challenges to the
      biomedical researchers - What are all these non-coding RNAs, how did they work,
      and most importantly, what is the relationship between them and complex diseases?
      Although some ncRNAs have been clearly characterized as risk biomarkers through
      biological experiments, there are still a limit number of known disease
      associated ncRNAs. Thus, bioinformatics methods have been widely used to predict
      candidate ncRNAs and disease associations. In this chapter, we will discuss
      several bioinformatics methods which have been developed to predict novel non
      coding biomarkers. With such methods and tools, the prioritization and
      identification of complex-implicated ncRNAs is becoming a reality.

PMID- 30191486
TI  - Genome-Wide Mapping of SNPs in Non-coding RNAs.
AB  - Non-coding RNAs (ncRNAs) are essential players that participate in multiple
      cellular processes. Cumulative evidence has linked ncRNA-related single
      nucleotide polymorphisms (SNPs) to various human diseases. However, the knowledge
      of ncRNA-related SNPs and their potential functional mechanisms in human disease
      need to be further discovered. Here, we reviewed related studies on functional
      SNPs in two main types of ncRNA, microRNAs (miRNAs) and long non-coding RNAs
      (lncRNAs), with a particular focus on these ncRNA-related SNPs as novel risk
      factor of disease etiology. These studies will gain global insights into the
      relationship between ncRNAs and their functions.

PMID- 30191487
TI  - Profiling DNA Methylation Patterns of Non-coding RNAs (ncRNAs) in Human Disease.
AB  - Although non-coding RNAs (ncRNAs) are commonly considered modulators in human
      disease, revealing the methylation pattern of ncRNA is still a challenging task.
      In this chapter, we (1) introduced a strategy of constructing DNA methylation
      profiles for ncRNAs by reannotating data of DNA methylation arrays; (2)
      identified methylation patterns of ncRNAs in cancers by classifying ncRNAs into
      two categories and three subcategories, according to their promoter methylation
      patterns in tumors; (3) identified lncRNAs with promoter methylation patterns
      that were associated with cancer status, subtype, or prognosis for several
      cancers by integrating cancer subtype data and patient clinical information;
      Furthermore, a panel of ncRNAs were identified as biomarkers that discriminated
      between disease phenotypes. The potential functions of aberrantly methylated
      ncRNAs were predicted, suggesting that ncRNAs and coding genes cooperatively
      mediate pathway dysregulation during the development and progression of breast
      cancer.

PMID- 30191488
TI  - Aberrant Epigenetic Modifications of Non-coding RNAs in Human Disease.
AB  - Non-coding RNAs, especially lncRNAs, have emerged as key components in histone
      modification. The alterations in the epigenetic modifications of lncRNAs underlie
      some human disorders ranging from neurodegeneration to cancer. To characterize
      the epigenetic modifications of lncRNAs, we first constructed the histone
      modification maps of various epigenetic markers across different cell lines.
      Then, we developed a method to identify epigenetically regulated lncRNAs and
      their response genes by integrating large scale epigenetic and transcriptional
      profiles. Our results showed that epigenetic alterations at the promoters of
      lncRNAs can influence their expression and the negative response genes of most
      epigenetically regulated lncRNAs were enriched for PRC2-binding genes. At last,
      we inferred some lncRNAs with aberrant epigenetic modifications in glioblastoma
      and Alzheimer's disease, and proved that theses lncRNAs may contribute to the
      initiation of human diseases.

PMID- 30191489
TI  - Computationally Modeling ncRNA-ncRNA Crosstalk.
AB  - Our understanding of complex gene regulatory networks have been improved by the
      discovery of ncRNA-ncRNA crosstalk in normal and disease-specific physiological
      conditions. Previous studies have proposed numerous approaches for constructing
      ncRNA-ncRNA networks via ncRNA-mRNA regulation, functional information, or
      phenomics alone, or by combining heterogeneous data. Furthermore, it has been
      shown that ncRNA-ncRNA crosstalk can be rewired in different tissues or specific
      diseases. Therefore, it is necessary to integrate transcriptome data to construct
      context-specific ncRNA-ncRNA networks. In this chapter, we elucidated the
      commonly used ncRNA-ncRNA network modeling methods, and highlighted the need to
      integrate heterogeneous multi-mics data. Finally, we suggest future directions
      for studies of ncRNAs crosstalk. This comprehensive description and discussion
      elucidated in this chapter will provide constructive insights into ncRNA-ncRNA
      crosstalk.

PMID- 30191490
TI  - Computational Inferring of Risk Subpathways Mediated by Dysfunctional Non-coding
      RNAs.
AB  - Non-coding RNAs mediated core elements of pathways contributes to the disorder of
      biological function in diseases. Identification of non-coding RNAs mediated
      subpathways not only can help for deciphering the pathogenic mechanism of complex
      diseases, but also can gain insight into the functional roles of non-coding RNAs
      in human diseases. Here, we summarized the general steps for identifying non
      coding RNA mediated subpathways and overviewed two of our previously developed
      methods, Subpathway-GMir and Subpathway-LNCE, which were designed to identify
      miRNAs and lncRNAs mediated risk subpathways respectively. We identified the key
      subpathway regions by integrating non-coding RNA-target gene associations,
      interesting genes and non-coding RNAs and pathway topologies. By applying methods
      to several disease datasets, we confirmed that our methods is effective in
      identifying risk subpathways and also can help uncover key non-coding RNAs in
      diseases. Additionally, reproducibility and robustness analysis demonstrated our
      methods are reliable.

PMID- 30191491
TI  - Computational Identification of Cross-Talking ceRNAs.
AB  - Competing endogenous RNAs (ceRNAs) are kinds of RNAs that regulate each other at
      post-transcription level through competing for miRNA regulators. CeRNA-ceRNA
      networks provide another type of function for protein-coding mRNAs, which link
      non-coding RNAs such as miRNA, long non-coding RNA, pseudogenes and circular
      RNAs. In this chapter, we will introduce the definition of ceRNAs, mainly provide
      the computational method to predict ceRNA interactions in general condition and
      complex diseases. In addition, we also illustrated several computational methods
      that are commonly used to identify the perturbed ceRNA networks in human diseases
      compared to normal conditions. Finally, we also summarized the principles of
      methods that integrated ceRNA theory to identify human disease biomarkers.
      Understanding of RNA-RNA crosstalk will provide significant insights into gene
      regulatory network that has been implicated in human development and/or diseases.

PMID- 30191492
TI  - Prediction of Non-coding RNAs as Drug Targets.
AB  - MiRNA is a class of small non-coding RNA molecule that regulates gene expression
      at post-transcriptional level. Increasing evidences show aberrant expression of
      miRNAs in a variety of diseases. Targeting the dysregulated miRNAs with small
      molecule drugs has become a novel therapeutics for many human diseases,
      especially cancers. In this chapter, we introduced a series of computational
      studies for prediction of small molecule and miRNA associations. Based on
      different hypotheses, such as transcriptional response similarity, functional
      consistence or network closeness, the small molecule-miRNA networks were
      constructed and further analyzed. In addition, several resources that collected
      experimentally validated relationships or computational predicted associations
      between small molecules and miRNAs were provided. Collectively, these
      computational frameworks and databases pave a new way for miRNA-targeted therapy
      and drug repositioning.

PMID- 30191493
TI  - Methods for Identification of Protein-RNA Interaction.
AB  - The importance of RNA-protein interactions in regulation of mRNA and non-coding
      RNA function is increasingly appreciated. With the development of next generation
      high-throughput sequencing technologies, a variety of methods have been proposed
      to comprehensively identify RNA-protein interactions. In this chapter, we
      discussed the traditional and state-of-the-art technologies that were used to
      study RNA-protein interaction, including experimental and computational methods.
      To help highlight the biological significance of RNA-protein interaction in
      complex diseases, online resources on RNA-protein interactions were briefly
      discussed. Finally, we discussed the interaction among noncoding RNAs (such as
      long noncoding RNAs and microRNAs) and proteins, as well as the dysregulation of
      RNA-protein interaction in complex diseases. These summarization will ultimately
      provide a more complete picture for understanding of the function of RNA-protein
      interactions, including how these interaction assembled and how they modulate
      cellular function in complex diseases.

PMID- 30191494
TI  - The association of PRECISE-DAPT score with development of contrast-induced
      nephropathy in patients with ST-elevation myocardial infarction undergoing
      primary percutaneous coronary intervention.
AB  - Given that parameters used in the calculation of the PRECISE-DAPT risk score are
      important contributors to contrast-induced nephropathy (CIN) development, we
      hypothesized that the PRECISE-DAPT risk score would show good accuracy for
      predicting CIN in patients with ST-elevation myocardial infarction (STEMI)
      undergoing primary percutaneous coronary intervention (PCI). Therefore, in this
      study, we aimed to determine the predictive value of the admission PRECISE-DAPT
      score for the occurrence of CIN in patients with STEMI treated with primary PCI.
      After evaluation regarding with exclusion criteria, 1280 patients were,
      respectively, enrolled in the study. The primary end-point was the incidence of
      CIN. The PRECISE-DAPT score of CIN group was higher than the non-CIN group [31
      (24-41) vs. 14 (9-23), p < 0.001, respectively]. In multivariate logistic
      regression analysis, PRECISE-DAPT score was independently associated with the
      development of CIN [odds ratio (OR) 1.090, 95% confidence interval (CI) 1.066
      1.114, p < 0.001]. A receiver-operating characteristic (ROC) analysis was drawn
      to show the best cut-off value of the PRECISE-DAPT score to predict CIN was >= 21
      with 81.3% sensitivity and 72.7% specificity [area under curve (AUC): 0.834; 95%
      CI 0.812-0.854; p = 0.017]. The PRECISE-DAPT score may be a significant
      independent predictor of CIN in patients with STEMI treated with primary PCI.
      Therefore, follow-up of patients with higher PRECISE-DAPT score should be
      performed more cautiously, and it should be noted that the development of CIN
      risk of these patients group is high.

PMID- 30191496
TI  - Diagnosis of Riga-Fede Disease.

PMID- 30191495
TI  - Taurine and Neonatal Nutrition.

PMID- 30191497
TI  - Efficient isolation and observation of the most complex human commensal, Demodex
      spp.
AB  - Demodex spp. mites are an often neglected member of the human skin microbiome.
      Mostly they are commensals, although their pathophysiological role in rosacea,
      spinulosis folliculorum, and other skin diseases is recognized. Little is known
      about their life cycle, biology, and physiology. Demodex mites cannot be
      cultivated in vitro, thereby complicating research immensely. The manual
      extraction from human sebum is laborious and death can only be detected by
      surrogate markers like ceased movement or loss of fluorescence. Here we present a
      new approach for the extraction of larger mite numbers and the hitherto most
      precise way to detect death. The extraction of mites from sebum and debris by
      hand can be accelerated by a factor 10 using sucrose gradient centrifugation,
      which is well tolerated by the mites. Staining with propidium iodide allows for
      easy identification of dead mites, excluding frail mites that stopped moving, and
      has no negative effect on overall mite survival. We anticipate our methods to be
      a starting point for more sophisticated research and ultimately in vitro
      cultivation of Demodex spp. mites.

PMID- 30191498
TI  - Homocysteine and Folate in Inflammatory Bowel Disease: Can Reducing Sulfur Reduce
      Suffering?

PMID- 30191500
TI  - Sharing lives, sharing bodies: partners negotiating breast cancer experiences.
AB  - By drawing on Jean-Luc Nancy's philosophy of ontological relationality, this
      article explores what it means to be a 'we' in breast cancer. What are the
      characteristics-the extent and diversity-of couples' relationally lived
      experiences of bodily changes in breast cancer? Through analyzing duo interviews
      with diagnosed women and their partners, four ways of sharing an embodied life
      are identified. (1) While 'being different together', partners have different,
      albeit connected kinds of experiences of breast cancer. (2) While 'being there
      for you', partners take care of each other in mutually dependent ways. (3) While
      'being reconnected to you', partners (re-)relate to each other through intimacy
      and sexuality. (4) While 'being like you', partners synchronize their embodied
      daily lives to one another, sometimes up to the point that the self cannot be
      distinguished from the other anymore. These ways reveal that being a 'we'
      involves complex affective, bodily encounters in which the many fault lines that
      both separate partners into individual selves and join them together as a unity
      are continuously reshaped and negotiated. Being a 'we' may be understood as
      something we have to do. Therefore, in being true to the legacy of Nancy, we
      argue at the end of this article for a sensible praxis of sharing a life and
      body, particularly in breast cancer.

PMID- 30191499
TI  - Silybin Alleviates Hepatic Steatosis and Fibrosis in NASH Mice by Inhibiting
      Oxidative Stress and Involvement with the Nf-kappaB Pathway.
AB  - BACKGROUND AND AIM: Silybin is the major biologically active compound of
      silymarin, the standardized extract of the milk thistle (Silybum marianum).
      Increasing numbers of studies have shown that silybin can improve nonalcoholic
      steatohepatitis (NASH) in animal models and patients; however, the mechanisms
      underlying silybin's actions remain unclear. METHODS: Male C57BL/6 mice were fed
      a methionine-choline deficient (MCD) diet for 8 weeks to induce the NASH model,
      and silybin was orally administered to the NASH mice. The effects of silybin on
      lipid accumulation, hepatic fibrosis, oxidative stress, inflammation-related gene
      expression and nuclear factor kappa B (NF-kappaB) activities were evaluated by
      biochemical analysis, immunohistochemistry, immunofluorescence, quantitative real
      time PCR and western blot. RESULTS: Silybin treatment significantly alleviated
      hepatic steatosis, fibrosis and inflammation in MCD-induced NASH mice. Moreover,
      silybin inhibited HSC activation and hepatic apoptosis and prevented the
      formation of MDBs in the NASH liver. Additionally, silybin partly reversed the
      abnormal expression of lipid metabolism-related genes in NASH. Further study
      showed that the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling
      pathway played important roles in the silybin-derived antioxidant effect, as
      evidenced by the upregulation of Nrf2 target genes in the silybin treatment
      group. In addition, silybin significantly downregulated the expression of
      inflammation-related genes and suppressed the activity of NF-kappaB signaling.
      CONCLUSIONS: Silybin was effective in preventing the MCD-induced increases in
      hepatic steatosis, fibrosis and inflammation. The effect was related to
      alteration of lipid metabolism-related gene expression, activation of the Nrf2
      pathway and inhibition of the NF-kappaB signaling pathway in the NASH liver.

PMID- 30191501
TI  - Behavioral adjustment to asymmetric reward availability among children with and
      without ADHD: effects of past and current reinforcement contingencies.
AB  - Altered reinforcement sensitivity is hypothesized to underlie symptoms of
      attention deficit hyperactivity disorder (ADHD). Here we evaluate the behavioral
      sensitivity of Brazilian children with and without ADHD to a change in reward
      availability. Forty typically developing children and 32 diagnosed with DSM-IV
      ADHD completed a signal-detection task in which correct discriminations between
      two stimuli were associated with different frequencies of reinforcement. The
      response alternative associated with the higher rate of reinforcement switched,
      without warning, after 30 rewards were delivered. The task continued until
      another 30 rewards were delivered. Both groups of children developed a response
      bias toward the initially more frequently reinforced alternative. This effect was
      larger in the control group. The response allocation of the two groups changed
      following the shift in reward availability. Over time the ADHD group developed a
      significant response bias toward the now more frequently reinforced alternative.
      In contrast, the bias of the control group stayed near zero after an initial
      decline following the contingency change. The overall shift in bias was similar
      for the two groups. The behavior of both groups of children was sensitive to the
      asymmetric reward distribution and to the change in reward availability. Subtle
      group differences in response patterns emerged, possibly reflecting differences
      in the time frame of reward effects and sensitivity to reward exposure.

PMID- 30191502
TI  - Causal Attributions for Obesity Among Patients Seeking Surgical Versus
      Behavioral/Pharmacological Weight Loss Treatment.
AB  - : Obesity is frequently attributed to causes such as laziness and lack of
      willpower and personal responsibility. The current study identified causal
      attributions for obesity among patients seeking bariatric surgery and compared
      them to those among patients seeking less invasive weight loss treatment
      (behavioral/pharmacological). The 16-item Causal Attributions for Obesity scale
      (CAO; rated 1-7) was administered to 102 patients seeking bariatric surgery
      (sample 1) and 178 patients seeking behavioral/pharmacological weight loss
      treatment (sample 2). Between-subjects analyses compared CAO ratings for the two
      samples. Results showed that behavioral factors were the highest-rated
      attributions in both samples. Sample 1 had higher ratings of biological and
      environmental factors than did sample 2. Overall, patients seeking bariatric
      surgery had a more complex conceptualization of obesity than did patients seeking
      behavioral/pharmacological treatment. TRIAL REGISTRATION: NCT02388568.

PMID- 30191503
TI  - Comprehensive Assessment of the Effects of Sleeve Gastrectomy on Glucose, Lipid,
      and Amino Acid Metabolism in Asian Individuals with Morbid Obesity.
AB  - BACKGROUND: Obesity-induced insulin resistance leads to abnormalities in glucose,
      lipid, and amino acid metabolism. Our study examined the differences in insulin
      mediated glucose, amino acid, and lipid metabolism between morbidly obese
      subjects with non-obese controls and the associated changes following sleeve
      gastrectomy (SG). METHODS: Non-obese controls and individuals with morbid obesity
      and scheduled for SG were recruited. Metabolic assessments were performed for all
      subjects at baseline and at 6 months after SG for eight subjects. The
      hyperinsulinemic-euglycemic clamp technique together with comprehensive
      metabolomic profiling was used to quantify insulin-mediated glucose, amino acid,
      and lipid metabolism. RESULTS: Eleven morbidly obese non-diabetic subjects
      scheduled for SG and nine non-obese controls were recruited. Compared to
      controls, obese subjects had significantly lower glucose uptake (4.4 +/- 0.6 vs.
      17.3 +/- 2.4 mg/kg FFM/min per MUU/mL.100) and higher concentration of branched
      chain amino acids (BCAAs, 332.5 +/- 26.8 vs. 235.3 +/- 11.0 MUM), non-esterified
      fatty acid (52.9 +/- 9.9 vs. 25.6 +/- 6.7 MUM), and lipid-related acylcarnitines
      (intermediate chain 389.8 +/- 32.5 vs. 285.9 +/- 20.5; long chain 301.7 +/- 22.1
      vs. 236.0 +/- 13.3 nM) during insulin clamp. Body weight significantly reduced at
      6 months after bariatric surgery (92.5 +/- 6.3 vs. 115.2 +/- 6.9 kg), together
      with improvements in insulin-mediated glucose uptake, and suppression of BCAAs,
      non-esterified fatty acids, and lipid-related metabolites. CONCLUSIONS: Morbid
      obesity in Asian individuals was associated with impairment in the regulatory
      actions of insulin on glucose, amino acid, and lipid metabolism, and these
      obesity-induced regulatory dysfunctions improved significantly 6 months after SG.

PMID- 30191504
TI  - Nutritional Deficiencies in Severe Obesity: a Multiethnic Asian Cohort.
AB  - BACKGROUND: Micronutrient deficiencies are highly prevalent in patients seeking
      metabolic-bariatric surgery (MBS), although literature remains scant in Asia. In
      this study, we assess the prevalence of nutritional deficiencies in patients with
      clinically severe obesity in Singapore and examine factors associated with the
      deficiencies. METHODS: This is a prospective, observational study of 577
      consecutive patients scheduled to undergo MBS. Nutritional profile including
      renal panel, calcium, phosphate, intact parathyroid hormone (iPTH), 25
      hydroxyvitamin D (25(OH)D), vitamin B12, folate, ferritin, iron studies,
      hemoglobin, albumin, and alkaline phosphatase were analyzed. RESULTS: Mean age
      was 40.6 +/- 10.3 years, 61.2% female, and mean BMI 42.4 +/- 8.4 kg/m2. 92.9% had
      suboptimal vitamin D levels; of which 25.6% had vitamin D insufficiency (25(OH)D
      < 30 mcg/L), 57.5% had vitamin D deficiency (25(OH)D < 20 mcg/L), and 9.8% had
      severe vitamin D deficiency (25(OH)D < 10 mcg/L). Younger age, female gender, and
      higher BMI were independent factors associated with lower 25(OH)D. There was an
      inverse relationship between iPTH and 25(OH)D, with an inflection point at
      25(OH)D of approximately 20 mcg/L. Folate deficiency was present in 31% and
      vitamin B12 deficiency in 9.5% of the cohort. Serum ferritin levels were low in
      29.3%. 25(OH)D, ferritin, serum iron, and albumin were also significantly higher
      in Chinese compared to Malay and Indian patients. CONCLUSION: Vitamin D
      deficiency was the most common micronutrient deficiency observed in this multi
      ethnic Asian cohort presenting for MBS. Ethnic differences in nutritional status
      were observed.

PMID- 30191505
TI  - Interleukin-6/STAT3 Signaling is Prominent and Associated with Reduced Overall
      Survival in p16 Negative Oropharyngeal Squamous Cell Carcinoma.
AB  - This study addresses the hypothesis that IL-6/STAT3 signaling is of clinical
      relevance in oropharyngeal squamous cell carcinoma (OPSCC). We evaluated
      relationships between key components of this pathway in tumors from a unique
      cohort of n = 59 fully annotated, treatment-naive patients with OPSCC. The
      multiplex Opal platform was utilized for immunofluorescence (IF) analysis of
      tissues to detect IL-6 and phosphorylated STAT3 (pSTAT3), taking into
      consideration its nuclear versus cytoplasmic localization. Abundant staining for
      both IL-6 and pSTAT3 was evident in tumor-rich regions of each specimen. IL-6
      correlated with cytoplasmic pSTAT3 but not nuclear or total pSTAT3 in this cohort
      of OPSCC tumors, regardless of p16 status (r = 0.682, p < 0.0001). There was a
      significant association between increased total pSTAT3, nuclear pSTAT3,
      cytoplasmic pSTAT3 and IL-6 in p16 negative tumors. Our data indicate STAT3
      phosphorylation was a key feature in p16-negative OPSCC tumors. When IL-6 data
      was stratified by median expression in tumors, there was no association with
      overall survival. In contrast, both total and nuclear pSTAT3 were significant
      predictors of poor overall and disease free survival. This strong inverse
      relationship with overall survival was present in p16 negative tumors for both
      total and nuclear pSTAT3, but not in p16 positive OPSCC tumors. Together these
      data indicate that activation of the STAT3 signaling pathway is a marker of p16
      negative tumors and relevant to OPSCC prognosis and a potential target for
      treatment of this more aggressive OPSCC sub-population.

PMID- 30191506
TI  - Epstein-Barr Virus-Positive Large Cell Neuroendocrine Carcinoma of the
      Nasopharynx: Report of One Case and Review of the Literature.
AB  - Epstein-Barr Virus (EBV)-positive neuroendocrine carcinoma (NEC) of the
      nasopharynx is exceedingly rare, only two cases have been reported in the
      literature. While EBV infection is strongly associated with nasopharyngeal
      carcinoma, which is carcinoma with squamous differentiation, the link between EBV
      and NEC is not well known, and can be diagnostically challenging. In this study,
      we report the third case of EBV-positive large cell NEC of nasopharynx with neck
      lymph node metastasis. The patient was treated with combined radiation and
      chemotherapy and showed complete clinical and radiological response. Similar
      treatment response has been reported in another patient with high stage EBV
      positive large cell NEC, suggesting that EBV status is an important prognostic
      factor. Recognition of this rare tumor is important for disease management and
      patient prognosis. We also review the literature about the clinical and
      pathologic presentation of neuroendocrine tumors of nasopharynx.

PMID- 30191507
TI  - Echocardiographic assessment of right ventricular function: current clinical
      practice.
AB  - Echocardiographic evaluation of right ventricular (RV) function is a challenge
      due to the complex anatomy of the RV. Several transthoracic echocardiographic
      methods have been suggested for the quantification of RV function. However, many
      of the parameters are time consuming and need dedicated hardware and software. We
      suspected that the majority of the established markers are not used on a wide
      basis. In a multinational online survey, we evaluated the use of current clinical
      standards for the quantification of RV function in clinical practice. Through the
      network of an Ultrasound Online Teaching Platform, echocardiographers were
      invited to participate in an open online survey. The participants were asked
      about the parameters (eyeballing, TAPSE, S', fractional area change, RIMP, 3D-EF,
      dp/dt, longitudinal strain) they used in clinical practice. A total of 1150
      participants from 109 countries completed the survey. Only eyeballing (72%),
      TAPSE (69%), and S' (31%) were commonly used in clinical routine. These methods
      were applied significantly less common in low-income economies when compared to
      high-income economies. Twenty-three percent of all participants stated to rely on
      eyeballing only, when evaluating RV function in clinical routine. New
      technologies, such as global longitudinal strain (3%) and 3D echocardiography
      (1%) were rarely applied independent of region and economic strength. Eyeballing
      and TAPSE are the most widely used methods in echocardiography for the assessment
      of RV function. Although advanced parameters such as longitudinal strain and 3D
      echocardiography were shown to be highly accurate, they are rarely used in
      clinical routine.

PMID- 30191509
TI  - Safety of Edoxaban 30 mg in Elderly Patients with Severe Renal Impairment.
AB  - BACKGROUND AND OBJECTIVE: Patients with atrial fibrillation (AF) and advanced
      chronic kidney disease (CKD) are at high risk of adverse events and are
      complicated to manage. There is little evidence on the effects of non-vitamin K
      oral anticoagulants in patients with severe CKD. Preliminary data in patients
      taking edoxaban whose creatinine clearance fell below 30 mL/min showed a low risk
      of stroke and major bleeding. The aim of our study is to test the safety of
      edoxaban 30 mg/day in patients with severe renal impairment with an estimated
      glomerular filtration rate (eGFR) of 15-29 mL/min. METHODS: We analyzed
      retrospective data from 46 patients who had documented AF with severe renal
      impairment (eGFR between 15 and 29 mL/min). The follow-up, characterized by
      clinical examination and blood analysis, was performed at 3, 6, and 12 months.
      The main endpoint was the incidence of major bleedings or clinically relevant non
      major (CRNM) bleedings or thromboembolic events. RESULTS: At the time of the data
      collection, the average follow-up was 9.13 +/- 3.0 months. There were no major
      bleedings, strokes, systemic embolisms, or cardiovascular deaths reported: one
      non-cardiac death and five minor hemorrhages occurred. No differences related to
      the severity of CKD were observed in the left ventricular ejection fraction at
      echocardiography and in the thrombotic and hemorrhagic risk profile. CONCLUSION:
      In this explorative study analyzing patients with severe CKD treated with
      edoxaban 30 mg once daily, no major bleeding or thrombotic events were observed.
      Some minor bleedings were observed. While additional studies are necessary to
      confirm the results of this exploratory study, edoxaban 30 mg once daily appears
      to be safe in patients with severe CKD.

PMID- 30191508
TI  - Direct and Indirect Costs of Immunoglobulin Replacement Therapy in Patients with
      Common Variable Immunodeficiency (CVID) and X-Linked Agammaglobulinemia (XLA) in
      Italy.
AB  - BACKGROUND: In Italy, there is scarce evidence on the epidemiological and
      economic burden induced by primary antibody deficiencies. OBJECTIVE: The aim of
      this study was to elaborate the available epidemiological and cost data in order
      to estimate the annual expenditure induced by the management of patients affected
      by the common variable immunodeficiency (CVID) and X-linked agammaglobulinemia
      (XLA) requiring immunoglobulin (Ig) replacement therapy. METHODS: A probabilistic
      cost-of-illness model was developed to estimate the number of patients with CVID
      and XLA, and the economic burden associated with their therapy in terms of direct
      or indirect costs. A systematic literature review was carried out to reveal both
      epidemiological and economic data. Furthermore, a probabilistic sensitivity
      analysis with 5000 Monte Carlo simulations was performed. RESULTS: The
      epidemiological model allowed us to estimate the number of prevalent patients
      affected by XLA and CVID in Italy in 2017, corresponding to 1885 (95% confidence
      interval [CI] 944-3145) and 133 (95% CI 115-152) patients, respectively. The
      estimated total expenditure for the treatment and management of patients with
      CVID and XLA requiring Ig replacement therapy amounts to ?42.68 million (95% CI
      ?14.38-?86.1 million). CONCLUSIONS: This information provides a comprehensive
      perspective of the economic issues, and facilitates better-informed public health
      decision making, in the management of CVID and XLA in Italy.

PMID- 30191510
TI  - Lymphadenopathy with coexisting normal architecture in malignant lymphoma.

PMID- 30191512
TI  - Infectious endocarditis with jump rope-like vegetations.

PMID- 30191511
TI  - Drug Treatment Accessed through the Criminal Justice System: Participants'
      Perspectives and Uses.
AB  - The criminal justice system has become a major pathway to drug treatment across
      the USA. Millions of criminal justice dollars are spent on an array of treatment
      programs for justice-involved populations, from pre-sentence diversionary
      programs to outpatient services for those on community supervision. This study
      uses 235 qualitative, longitudinal interviews with 45 people convicted of drug
      offenses to describe participants' perspectives on criminal justice-related drug
      treatment (programs within correctional facilities; court, probation, or parole
      ordered mandates and referrals; and self-referrals made with the goal of reducing
      criminal justice involvement), beyond discourses about help with addiction.
      Interviews took place in New Haven, CT, between 2011 and 2014 every 6 months, for
      a maximum of five interviews with each participant. Many participants who were
      referred to drug treatment did not consider these programs appropriate for their
      needs, as many did not perceive themselves to have a drug problem, or did not
      consider substance use to be their primary problem. Frustrations regarding the
      ill-fitting nature of mandated programs were coupled with theories about non
      health-related policy goals of criminal justice-mandated drug treatment, such as
      prison overflow management and increased profit for the state. Nonetheless,
      participants used drug treatment to advance their own goals of coping with life's
      challenges, reducing their criminal justice system involvement, proving
      worthiness through rehabilitation, and accessing other resources. These
      participants' perspectives offer a wide lens through which to view the system of
      criminal justice-related drug treatment, a view that can guide us in critically
      evaluating provision of drug treatment and developing more effective systems of
      appropriate rehabilitative services for people who are justice involved.

PMID- 30191513
TI  - Clinical and microbiological characteristics of adult invasive Haemophilus
      influenzae infections: results of a 14-year single-center experience from
      Hungary.
AB  - To describe the characteristics of adult invasive H. influenzae disease, 34
      patients diagnosed at a single tertiary center between 2004 and 2017 were
      analyzed in a retrospective case series study. The annual estimated incidence was
      0.1 cases/100.000 inhabitants. Dominant source of infection was pneumonia
      accompanied by sepsis (62%) and caused by nontypeable strains (74%) with low
      ampicillin resistance (14%). Survival (94%) and complication rates were high
      (35%). Main empirical treatments were ceftriaxone or levofloxacine.

PMID- 30191514
TI  - A resting state fMRI analysis pipeline for pooling inference across diverse
      cohorts: an ENIGMA rs-fMRI protocol.
AB  - Large-scale consortium efforts such as Enhancing NeuroImaging Genetics through
      Meta-Analysis (ENIGMA) and other collaborative efforts show that combining
      statistical data from multiple independent studies can boost statistical power
      and achieve more accurate estimates of effect sizes, contributing to more
      reliable and reproducible research. A meta- analysis would pool effects from
      studies conducted in a similar manner, yet to date, no such harmonized protocol
      exists for resting state fMRI (rsfMRI) data. Here, we propose an initial pipeline
      for multi-site rsfMRI analysis to allow research groups around the world to
      analyze scans in a harmonized way, and to perform coordinated statistical tests.
      The challenge lies in the fact that resting state fMRI measurements collected by
      researchers over the last decade vary widely, with variable quality and differing
      spatial or temporal signal-to-noise ratio (tSNR). An effective harmonization must
      provide optimal measures for all quality data. Here we used rsfMRI data from
      twenty-two independent studies with approximately fifty corresponding T1-weighted
      and rsfMRI datasets each, to (A) review and aggregate the state of existing
      rsfMRI data, (B) demonstrate utility of principal component analysis (PCA)-based
      denoising and (C) develop a deformable ENIGMA EPI template based on the
      representative anatomy that incorporates spatial distortion patterns from various
      protocols and populations.

PMID- 30191515
TI  - Antiproliferative and Apoptosis Triggering Potential of Paclitaxel-Based Targeted
      Lipid Nanoparticles with Enhanced Cellular Internalization by Transferrin
      Receptors-a Study in Leukemia Cells.
AB  - Leukemia is a typical blood cancer that is characterized by the numerous
      duplication and proliferation of white blood cells. The main aim of this study
      was to develop PTX-loaded multifunctional nanoparticles and target to leukemia
      cells. In this study, transferrin-decorated paclitaxel-loaded lipid nanoparticle
      (TPLN) was prepared with an aim to increase the chemotherapeutic efficacy in the
      leukemia cells. Results clearly showed the superior targeting potential of TPLN
      to the HL-60 cancer cells compared to that of the paclitaxel-loaded nanoparticles
      (PLN). To be specific, TPLN showed a significantly higher cytotoxic effect in the
      cancer cells compared to that of the PLN indicating the superior targeting
      efficiency of the Tf-decorated nanoparticle system. The IC50 value of TPLN was
      0.45 MUg/ml compared to 2.8 MUg/ml for PLN. TPLN induced a most remarkable
      apoptosis of the cancer cells and much of the cells were distorted with huge
      presence of the apoptotic body formation. Importantly, TPLN showed a remarkable
      reduction in the viable cells proportion to ~ 65% with around ~ 30% apoptosis
      cells (early and late apoptosis). Overall, results clearly showed the targeting
      potential of ligand-conjugated lipid nanoparticle system to the leukemia cells
      that might pave the way for the successful cancer treatment.

PMID- 30191517
TI  - Treating Fatigue in Rheumatoid Arthritis: Does Patient Age Matter?
AB  - Clinically relevant fatigue is common in patients with rheumatoid arthritis (RA)
      and might be expected to be related to patient age and disease severity. This
      review provides a brief introduction to fatigue as a patient-reported outcome
      that contributes significantly to burden of disease, with a focus on the evidence
      in elderly patients, and gives an overview of our current understanding of the
      factors that contribute to fatigue. We summarize the evidence for the effects of
      pharmacological (disease-modifying anti-rheumatic drugs, DMARDs) and non
      pharmacological interventions for fatigue. The underlying pathophysiology of
      fatigue is complex and often multifactorial. The experience of fatigue varies
      between individuals, and subtypes of fatigue are increasingly being recognized.
      Fatigue can therefore be challenging to recognize and quantify. Recent systematic
      reviews have shown that fatigue can be improved as a result of treatment with
      traditional and biological anti-rheumatic drugs, and also with non
      pharmacological approaches (physical activity, psychosocial interventions). Age
      does not appear to be of major importance for fatigue in RA, and similar
      strategies for treating fatigue apply to all age groups, including the elderly.

PMID- 30191518
TI  - Viscoelastic testing: It's not the measurement, it's what you do with it!

PMID- 30191516
TI  - Association of Anticholinergic Drug Burden with Cognitive and Functional Decline
      Over Time in Older Inpatients: Results from the CRIME Project.
AB  - BACKGROUND: Medications with anticholinergic properties, although widely used,
      may negatively affect cognitive and functional status in older patients. To date
      there is still no standardized method to quantify anticholinergic exposure. We
      analyzed the relationship of two different tools for the evaluation of the
      anticholinergic drug burden with cognitive and functional impairment in a sample
      of older hospitalized patients. METHODS: A retrospective and longitudinal
      analysis with 1-year follow-up of 1123 older hospitalized patients enrolled in
      seven Italian acute care wards was conducted. We assessed anticholinergic burden
      with the Anticholinergic Cognitive Burden (ACB) and Anticholinergic Risk Scale
      (ARS). Cognitive and functional status were evaluated at hospital discharge and
      during follow-up (3, 6, 12 months) using the Mini Mental State Examination (MMSE)
      and five basic activities of daily living (ADLs). Associations between
      anticholinergic burden and cognitive decline and incident disability were
      estimated using linear regression models for repeated measures and logistic
      models, respectively. RESULTS: The mean age of the study population was 81 +/-
      7.5 years. ACB and ARS classifications showed low correlation (Spearman's rho =
      0.39-0.43). Anticholinergic burden increased during hospitalization and was
      associated with cognitive and functional status. Patients with an ARS of >= 1 at
      discharge had  significantly lower baseline MMSE scores (ARS = 0: 23.1; ARS >= 1:
      20.8; p = 0.002) and during follow-up presented a  significantly steeper MMSE
      score decline (- 0.15/month). Moreover, patients with an ACB of >= 1 at discharge
      had an almost threefold increased risk of developing disability (odds ratio 2.77,
      95% confidence interval 1.39-5.54). CONCLUSIONS: ACB and ARS have only a moderate
      degree of correlation. Use of drugs with anticholinergic properties in elderly
      patients is independently associated with cognitive and functional decline.

PMID- 30191519
TI  - Knowledge, Attitudes, and Practices of Breast Cancer Screening Methods Among
      Female Patients in Primary Healthcare Centers in Najran, Saudi Arabia.
AB  - The aim of the present study was to evaluate the knowledge, attitude, and
      practice of breast cancer screening methods among female patients attending five
      primary healthcare centers in Najran, Saudi Arabia. A cross-sectional survey was
      conducted on 500 female patients, and a direct interview questionnaire was used
      to collect data. Our results indicated a low knowledge about breast cancer,
      breast self-examination, mammogram and clinical breast examination was 54.4%,
      56%, 90.4%, and 83.8%, respectively. Nineteen percent of patients demonstrated a
      high knowledge of breast self-examination. Breast self-examination was performed
      by 35% of patients, whereas 15% of patients received mammograms and 19.8%
      clinical breast examinations. The most common barrier for screening methods of
      breast cancer was that patients were unaware of half of the screening methods. A
      total of 20.6% of women did not perform breast self-examinations because they
      were not well trained, and 26.4% of women did not receive clinical breast
      examinations because there was no female doctor available. The main source of
      information among the women patients was social media (52.4%), whereas 8.8%
      received information through their healthcare provider. In summary, the majority
      of women demonstrated poor knowledge about breast cancer and screening methods.
      Additional effort should be put forth through women's healthcare providers to
      increase the awareness of breast cancer screening. That means we need to continue
      emphasizing the importance of primary healthcare for early detection of breast
      cancer in the early stages.

PMID- 30191520
TI  - Effects of the herbicide Roundup(r) on the metabolic activity of Gammarus
      fossarum Koch, 1836 (Crustacea; Amphipoda).
AB  - Pesticides can easily reach surface waters via runoff and their potential to have
      detrimental impacts on freshwater organisms is high. Not much is known about how
      macroinvertebrates react to glyphosate contamination. In this study we
      investigated lethal and sublethal effects of the exposure of Gammarus fossarum to
      Roundup(r), a glyphosate-based herbicide. The LC10 and LC50 values after 96 h
      were determined to be 0.65 ml/L Roundup(r) (230 mg/L glyphosate) and 0.96 ml/L
      Roundup(r) (340 mg/L glyphosate), respectively. As a sublethal measure of
      toxicity we conducted eight experiments with the feeding activity and the
      respiratory electron transport system (ETS) activity as endpoints. All
      experiments lasted seven days. Although the LC10 concentration of Roundup(r) was
      used for the feeding activity tests, 49% of the gammarids died before the end of
      the experiments, which is inconsistent with the calculated LC10-values. The
      feeding activity was significantly higher in Roundup(r)-enriched water (mean =
      0.18 mg/mg x d) in comparison to pure spring water (mean = 0.079 mg/mg x d). No
      significant difference was observed between the ETS activity, which was
      determined after 24, 48 or 96 h after the start of the experiment, of the
      gammarids in Roundup(r) solution and in the control. The LC-values determined
      here are rather high, and exceed background glyphosate concentrations in most
      anthropogenically influenced surface waters. The increased feeding activity when
      exposed to Roundup(r) in combination with an unchanged ETS activity suggests
      effects on the metabolic efficiency of G. fossarum. We argue that Roundup(r)
      enhances the anabolic activity (feeding activity) in order to maintain the
      catabolic activity (ETS activity).

PMID- 30191521
TI  - Assessment of whole-sediment chronic toxicity using sub-lethal endpoints with
      Monocorophium insidiosum.
AB  - A whole-sediment test with the infaunal amphipod Monocorophium insidiosum has
      been developed to assess the long-term effects exerted by sediment contamination
      on survival, growth rates and attainment of sexual maturity. Juvenile amphipods
      were exposed for 28 days to a control sediment (native sediment) and three
      sediment samples collected in sites of the Venice Lagoon, characterized by
      contamination levels ranging from low to moderate, and absence of acute toxicity
      toward amphipods. Growth rate was estimated as daily length (MUm d-1) and weight
      increments (MUg d-1). The long-term exposure to the test sediments affected
      significantly both growth rate and attainment of sexual maturity of the females
      of M. insidiosum. In contrast, survival was high and uniform among all the
      samples, despite the contamination gradient. The results suggest growth to be the
      more reliable and statistically relevant endpoint. Attainment of sexual maturity,
      although allowed the identification of detrimental effects, was affected by a
      higher among-replicates variance as compared with growth rates, and thus less
      reliable than growth for the identification of impairments. The significant
      impairments observed both on growth and attainment of maturity evidenced the need
      to address the monitoring, also in the Lagoon of Venice, towards the assessment
      of the long-term effects on benthic species.

PMID- 30191522
TI  - Phase I study combining the aurora kinase a inhibitor alisertib with mFOLFOX in
      gastrointestinal cancer.
AB  - Overexpression and cellular mis-localization of aurora kinase A (AURKA) in
      gastrointestinal cancers results in chromosomal instability, activation of
      multiple oncogenic pathways, and inhibition of pro-apoptotic signaling.
      Inhibition of AURKA causes mitotic delays, severe chromosome congression, and
      activation of p53/p73 leading to cell death. Our preclinical data showed
      cooperative activity with the AURKA inhibitor alisertib and platinum agents in
      cell lines and xenografts, and suggested an optimal treatment window. Therefore,
      this study was designed to determine the maximum-tolerated dose (MTD) of
      alisertib in combination with modified FOLFOX (mFOLFOX), as this is a standard
      platinum-based therapy for gastrointestinal cancers. Standard 3 + 3 dose
      escalation was used, where the starting dose of alisertib was 10 mg twice daily
      (Days 1-3), with leucovorin (400 mg/m2) and oxaliplatin (85 mg/m2) on Day 2
      followed by continuous 46-h 5-FU (2400 mg/m2) infusion on Days 2-4 in 14-day
      cycles. Fourteen patients with advanced gastrointestinal cancers were enrolled
      and two doses explored; two patients were not evaluable for dose-limiting
      toxicity (DLT) and replaced. Two patients experienced DLTs at 20 mg of alisertib
      (Grade 3 fatigue (n = 2); Grade 3 nausea, vomiting, dehydration with
      hospitalization (n = 1)). MTD was 10 mg alisertib with 85 mg/m2 oxaliplatin and
      2400 mg/m2 5-FU. Most frequent toxicities were nausea (57%), diarrhea, fatigue,
      neuropathy, and vomiting (43%), and anorexia and anemia (36%); most were Grade 1
      2. One patient with colorectal cancer had a partial response of 12 evaluable
      patients, and four patients had stable disease. Alisertib in combination with
      mFOLFOX did not demonstrate unexpected side effects, but the regimen was only
      tolerable at the lowest dose investigated.

PMID- 30191523
TI  - Ketoconazole plus Lenalidomide in patients with Castration-Resistant Prostate
      Cancer (CRPC): results of an open-label phase II study.
AB  - Introduction Ketoconazole is CYP-17 inhibitor with demonstrated activity in men
      with castration-resistant prostate cancer (CRPC). Lenalidomide is an
      antiangiogenic and immunomodulatory agent with broad antitumor activity. We
      hypothesized that the modulation of the cellular immune response to apoptosis
      caused by ketoconazole may be increased with the addition of lenalidomide.
      Methods This is an open-label, non-randomized, single-arm phase II study
      evaluating the efficacy and safety of the combination of ketoconazole and
      lenalidomide in patients with CRPC. Treatment schema included standard
      ketoconazole 400 mg orally three times daily plus hydrocortisone orally (20 mg in
      the morning and 10 mg at night) in combination with lenalidomide 25 mg orally
      daily for 21 days in a 28-day cycle and aspirin 75 mg daily. The primary endpoint
      of this study was response (either by >= 50% PSA decline or objective disease
      assessed by RECIST v1.0). Exploratory endpoints included changes in T cell,
      dendritic cell (DC) marker counts, and their correlation with PSA response to
      treatment. Results A total of 34 CRPC patients, median age 69 years, 76% ECOG 0
      and 76% with metastases participated in the study. Patients received a median of
      2 cycles (range 1-35); nine patients (26%) received >10 cycles of treatment. PSA
      responses were observed in 17 patients (50%) with 11 patients (32%) achieving a
      PSA decline of >90%. Among the 9 patients with measurable disease, 2 patients
      (22%) had PR and 2 other (22%) had SD as best response. Median time to failure
      (TTF) was 2.7 months (range 0.2-32.8); and 8 patients were treated for >= 15
      months. Most common adverse events included fatigue (76%), skin reactions (62%),
      lymphopenia (44%) and anemia (44%). One possible treatment-related death was
      noted. For 16 patients with available serial correlative data, there was a
      significant increase in the dendritic cells subsets BDCA-1 (+146.7, -20.1 to
      +501.1%, p = 0.018) and BDCA-3 (39.8%, -100 to 282.6%, p = 0.001) after 8 weeks
      of treatment. No association between immune cell counts and PSA response at 8
      weeks was observed. Conclusion The combination of ketoconazole and lenalidomide
      was well tolerated but did not meet the primary endpoint of response, despite
      durable responses were observed in a selected group of patients. Although
      ketoconazole has now been replaced with more active novel agents, the combination
      of novel CYP-17 inhibitors with agents capable of modulating the immune system
      warrants further prospective investigation. NCT00460031.

PMID- 30191524
TI  - The effect of comorbidities on outcomes in colorectal cancer survivors: a
      population-based cohort study.
AB  - PURPOSE: To examine the prevalence of comorbidities and the association of these
      comorbidities with demographics, tumor characteristics, treatments received,
      overall survival, and causes of death in a population-based cohort of colorectal
      cancer (CRC) patients. METHODS: Adult patients with stage I-III CRC diagnosed
      between 2004 and 2015 were included. Comorbidities were captured using Charlson
      comorbidity index. Causes of death were categorized using International
      Classification of Diseases, tenth revision codes. Patients were categorized into
      five mutually exclusive comorbid groups (cardiovascular disease alone, diabetes
      alone, cardiovascular disease plus diabetes, other comorbidities, or no
      comorbidities). Data were analyzed using descriptive statistics, Kaplan-Meier
      survival analyses, and Cox proportional hazards models. RESULTS: There were
      12,265 patients. Mean follow-up was 3.8 years. Approximately one third of
      patients had a least one comorbidity, with cardiovascular disease and diabetes
      being most common. There were statistically significant differences across
      comorbid groups on treatments received and overall survival. Those with
      comorbidity had lower odds of treatment and greater risk of death than those with
      no comorbidity. Those with cardiovascular disease plus diabetes fared the worst
      for prognosis (median overall survival 3.3 [2.8-3.7] years; adjusted HR for
      death, 2.27, 95% CI 2.0-2.6, p < .001). Cardiovascular disease was the most
      common cause of non-CRC death. CONCLUSIONS: CRC patients with comorbidity
      received curative intent treatment less frequently and experienced worse outcomes
      than patients with no comorbidity. Cardiovascular disease was the most common
      cause of non-cancer death. IMPLICATIONS FOR CANCER SURVIVORS: Management of
      comorbidities, including healthy lifestyle coaching, at diagnosis and into
      survivorship is an important component of cancer care.

PMID- 30191526
TI  - Analysis of the results of empirical research and surveys of perceived indoor
      temperature depending on gender and seasons.
AB  - The indoor thermal condition tests were conducted as real and declared by the
      respondents. The tests were carried out in the laboratory room in Bialystok. The
      object is a detached, two-storey building with a cellar. The tests were carried
      out from February to May 2015. In 1 week, on average, ten measurement series were
      carried out. During one experiment series, there were between 10 and 15 students
      present in the room. The aim of the publication is to analyze the results of
      declared perceived temperature tests in the room depending on the gender, the
      season and indoor and outdoor temperature conditions. On the basis of statistical
      analysis of the test results, it was found that in the analyzed age group, the
      perceived temperature declared in the room is not affected by the respondent's
      gender. The conclusion is that the temperature sensations of young (and probably
      healthy) people who do not do physical work are similar, regardless of gender.
      Differences between the average perceived temperature in the room, declared by
      all respondents in winter and declared in spring are statistically significant.
      The indoor perceived temperature declared in the winter is almost constant and
      does not depend on the temperature of the perceived temperature of outdoor air.

PMID- 30191525
TI  - Water quality modeling of a prairie river-lake system.
AB  - Eutrophication of an under-ice river-lake system in Canada has been modeled using
      the Water Quality Analysis Simulation Program (WASP7). The model was used to
      assess the potential effect on water quality of increasing inter-basin transfer
      of water from an upstream reservoir into the Qu'Appelle River system. Although
      water is currently transferred, the need for increased transfer is a possibility
      under future water management scenarios to meet water demands in the region.
      Output from the model indicated that flow augmentation could decrease total
      ammonia and orthophosphate concentrations especially at Buffalo Pound Lake
      throughout the year. This is because the water being transferred has lower
      concentrations of these nutrients than the Qu'Appelle River system, although
      there is complex interplay between the more dilute chemistry, and the potential
      to increase loads by increasing flows. A global sensitivity analysis indicated
      that the model output for the lake component was more sensitive to input
      parameters than was the model output of the river component. Sensitive parameters
      included dissolved organic nitrogen mineralization rate, phytoplankton nitrogen
      to carbon ratio, phosphorus-to-carbon ratio, maximum phytoplankton growth rate,
      and phytoplankton death rate. Parameter sensitivities on output variables for the
      lake component were similar for both summer (open water) and winter (ice
      covered), whereas those for the river component were different. The complex
      interplay of water quality, ice behaviors, and hydrodynamics of the chained river
      lake system was all coupled in WASP7. Mean absolute error varied from 0.03-0.08
      NH4-N/L for ammonium to 0.5 to1.7 mg/L for oxygen, and 0.04-0.13 NO3-N/L for
      nitrate.

PMID- 30191527
TI  - Remediation potential of caffeine, oxybenzone, and triclosan by the salt marsh
      plants Spartina maritima and Halimione portulacoides.
AB  - Pharmaceuticals and personal care products (PPCPs) have attracted increasing
      concern during the last decade because of their widespread uses and continuous
      release to the aquatic environment. This work aimed to study the distribution of
      caffeine (CAF), oxybenzone (MBPh), and triclosan (TCS) when they arrive in salt
      marsh areas and to assess their remediation potential by two different species of
      salt marsh plants: Spartina maritima and Halimione portulacoides. Experiments
      were carried out in the laboratory either in hydroponics (sediment elutriate) or
      in sediment soaked in elutriate, for 10 days. Controls without plants were also
      carried out. CAF, MBPh, and TCS were added to the media. In unvegetated sediment
      soaked in elutriate, CAF was mainly in the liquid phase (83%), whereas MBPh and
      TCS were in the solid phase (90% and 56%, respectively); the highest remediation
      was achieved for TCS (40%) and mainly attributed to bioremediation. The presence
      of plants in sediment soaked in elutriate-enhanced PPCPs remediation, decreasing
      CAF and TCS levels between approximately 20-30% and MBPh by 40%.. Plant uptake,
      adsorption to plant roots/sediments, and bio/rhizoremediation are strong
      hypothesis to explain the decrease of contaminants either in water or sediment
      fractions, according to PPCPs characteristics.

PMID- 30191528
TI  - Adsorption behavior of chloroform, carbon disulfide, and acetone on coconut shell
      derived carbon: experimental investigation, simulation, and model study.
AB  - The adsorption performances of chloroform (TCM), carbon disulfide (CDS), and
      acetone (CP) were investigated and compared over self-prepared coconut shell
      derived carbon (CDC) to study the adsorption behavior and mechanism of heteroatom
      (Cl, S, O)-containing volatile organic compounds (VOCs). The result indicates
      that the adsorption capacity of three typical VOCs obeys the sequence: TCM (361
      mg/g) > CDS (194 mg/g) > CP (37 mg/g). However, desorption experiments show that
      adsorption intensity follows the order: CDS (165  degrees C) > TCM (147  degrees
      C) > CP (130  degrees C). The influence of surface oxygen-containing functional
      groups over CDC on adsorption performance was also studied by temperature
      programmed desorption (TPD) and in situ DRIFT spectra. It is implied that
      carbonyl in lactone and benzoquinonyl of CDC could affect VOC adsorption
      intensity by conjugation effect. Furthermore, adsorption isotherms of three VOCs
      were obtained through Grand Canonical Monte Carlo (GCMC) simulation and then
      fitted by classical isothermal models. Furthermore, the total adsorption
      potentials are calculated by potential theory, and the result follows the order:
      TCM (- 2.18 kJ/mol) > CDS (- 2.1 kJ/mol) > CP (- 1.5 kJ/mol). It is believed that
      the effect of magnetic susceptibility (chi) is more crucial than polarizability
      (?) and the distance r between the interacting molecules for the potential
      difference.

PMID- 30191529
TI  - Transcriptome analysis to identify the Ras and Rap1 signal pathway genes involved
      in the response of TM3 Leydig cells exposed to zearalenone.
AB  - The mechanism of action of zearalenone (ZEA) in inducing germ cell tumors is
      unclear, and little is known about the change in the transcriptome of germ cells
      after ZEA exposure. To explore the molecular basis of the ZEA oncogene, we
      examined the median lethal concentration (50 MUmol/L) and pro-apoptotic effect of
      ZEA on TM3 Leydig cells by MTT and TUNEL assay. Subsequently, we investigated the
      genetic changes in the transcriptome of TM3 Leydig cells exposed to 50 MUmol/L
      ZEA. The transcriptome sequencing results show that 772 genes are significantly
      down-regulated, while 204 genes are significantly up-regulated. Gene ontology
      (GO) enrichment analysis shows that ZEA has a major effect on the connective
      function, cell composition, cell cycle, and energy metabolism of the TM3 Leydig
      cells. Using the results of the GO and Kyoto Encyclopedia of Genes and Genomes
      (KEGG) enrichment analyses, we select the Ras and Rap1 signaling pathways that
      are closely related to the occurrence of cancer. The differentially expressed
      genes visualized in the KEGG pathway were selected for RT-qPCR differential gene
      expression validation. The results show that the gene expression results are
      consistent with the transcriptome sequencing results. This study thus provides a
      theoretical molecular basis for the mechanism of ZEA carcinogenesis.

PMID- 30191531
TI  - Living-donor lung transplantation after surgical repair of transposition of the
      great arteries.
AB  - Pediatric pulmonary hypertension after surgery for congenital heart disease is a
      significant complication. We present a case of living-donor lung transplantation
      for a 12-year-old girl with pulmonary hypertension after surgical repair of
      transposition of great arteries. Despite repairing the transposition of great
      arteries, her growth was severely restricted because of progressive pulmonary
      hypertension; thus, lung transplantation was discussed. Standard bilateral lobar
      transplantation seemed unfeasible due to oversized grafts, so we performed a
      single lobar transplantation. Unexpectedly, she developed complications and died
      3 months postoperatively despite another emergent lobar transplantation. We
      discussed the challenges and potential solutions regarding lobar size
      mismatching.

PMID- 30191530
TI  - Aggregation, sedimentation, and dissolution of CuO and ZnO nanoparticles in five
      waters.
AB  - With the accelerated application of copper oxide (CuO) and zinc oxide (ZnO)
      nanoparticles (NPs) in commercial products, concerns about the potential impacts
      on the environment have been growing. Environmental behaviors of NPs are expected
      to significantly influence their fate and ecological risk in the aquatic
      environment. In this study, the environmental behaviors of two metallic NPs (CuO
      and ZnO NPs), including aggregation, sedimentation, and dissolution, were
      systematically evaluated in five representative waters (pool water, lake water,
      rainwater, tap water, and wastewater) with varying properties. Remarkable
      aggregation, sedimentation, and dissolution were observed for both metallic NPs,
      among which ZnO NPs exhibited greater influence. CuO (ZnO) NPs aggregated to 400
      (500) nm, 500 (900) nm, and 800 (1500) nm in lake water, wastewater, and tap
      water, respectively. The sedimentation rates of CuO and ZnO NPs in the five
      waters were ranked as tap water > wastewater > lake water > pool water >
      rainwater. The dissolution of CuO and ZnO NPs in waters follows a first-order
      reaction rate model and is affected by ionic type, ionic strength (IS), and NOM
      (natural organic matter) concentrations. Redundancy analysis (RDA) indicated that
      the aggregation and sedimentation of NPs have a strong correlation, insofar as
      the sedimentation rates increase with increasing aggregation rates. The
      aggregation and dissolution of NPs have a negative correlation, insofar as the
      dissolution rates reduce with increasing aggregation rates. The aggregation,
      sedimentation, and dissolution of NPs can be influenced by ionic types, IS, and
      TOC in waters, among which, TOC may the dominant factor.

PMID- 30191532
TI  - Palliation with a multimodality treatment including hypoxic pelvic perfusion for
      unresectable recurrent rectal cancer: outcomes based on a retrospective study.
AB  - Patients with unresectable recurrent rectal cancer that progresses after systemic
      chemotherapy and radiotherapy are candidates for palliation with hypoxic pelvic
      perfusion (HPP). The aim of this observational retrospective study was to
      evaluate if a multimodality treatment including HPP and targeted-therapy may be
      useful to prolong clinical responses and survival of these patients. From a
      cohort of 77 patients with unresectable recurrent rectal cancer in progression
      after standard treatments and submitted to HPP, 21 patients underwent repeat HPP
      using mitomycin C (MMC) at the dose of 25 mg/m2. After the last HPP, 7 patients
      received a targeted-therapy with cetuximab according to overexpression of
      epidermal growth factor receptor in recurrence cancer cells. The median overall
      survival of these 21 patients from the diagnosis of unresectable recurrent rectal
      cancer was 23 months (iqr 18-24). After the first HPP, the median survival of the
      21 patients until death or end of follow-up was 10 months (iqr 9-13). The 1-year
      and 2-year survival rates were 71.4%, and 4.8%, respectively. From the first HPP,
      age > 60 years, a recurrence shrinkage of at least 30% (partial response), and
      the addition of a post-HPP targeted-therapy with cetuximab significantly affected
      survival (P < 0.04). In conclusion, repeated MMC-HPP followed by targeted-therapy
      seems to be an effective palliative treatment for patients with unresectable
      recurrent rectal cancer in progression after systemic chemotherapy and radiation
      but the results of this study have to be confirmed by a larger phase III trial.

PMID- 30191533
TI  - Barbed vs conventional sutures in bariatric surgery: a propensity score analysis
      from a high-volume center.
AB  - The use of barbed sutures for constructing an anastomosis is favoured by a few
      bariatric surgeons as compared to conventional sutures. The aim of this study is
      to assess safety and efficacy of barbed sutures to close the gastric pouch
      jejunal anastomosis (GPJA) in laparoscopic gastric bypass (Roux-en-Y gastric
      bypass-RYGB, and One-Anastomosis gastric bypass-OAGB) using propensity score
      matching (PSM) analysis. A retrospective analysis of patients who underwent
      primary laparoscopic gastric bypasses between January 2012 and December 2017 was
      performed. Patients were divided into two different groups (RYGB-G and OAGB-G).
      PSM analysis was performed to minimize patient selection bias between the two
      types of sutures (barbed-BS and conventional-CS) in each group. A total of 808
      patients were reviewed. After PSM, 488 (244 BS vs 244 CS) patients in RYGB-G and
      48 in OAGB-G (24 BS vs 24 CS) patients were compared. Median operative time was
      significantly shorter (p < 0.001) for BS in RYGB-G. In OAGB-G, BS were associated
      with a shorter operative time, although no significant difference was observed (p
      = 0.183). Post-operative hospital stay was significantly shorter for BS in both
      the groups (p < 0.001). Post-operative 30th-day complications were comparable: no
      leakage or bleeding of GPJA was observed in BS groups. At median follow-up of
      28.78 months, no late complications were observed. Barbed sutures appear to be
      effective to close GPJA during gastric bypass and as safe as conventional suture.
      Further studies are necessary to draw definitive conclusions.

PMID- 30191534
TI  - May nutritional status worsen during hospital stay? A sub-group analysis from a
      cross-sectional study.
AB  - Hospital malnutrition is a detrimental prognostic factor regarding hospital
      mortality, complications, and length of stay. However, the role of
      hospitalization itself on nutritional status has not been fully elucidated. We
      report the results of a secondary analysis from the dataset of a recent cross
      sectional study at Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome,
      Italy. Data from patients evaluated at admission and discharge were collected and
      compared. One hundred thirty-nine patients were evaluated. Mean length of stay
      was 13.6 (+/- 7.7) days. Patients at risk of malnutrition, according to NRS-2002,
      were 75 (53.9%), while 63 (45.3%) were malnourished according to ESPEN Criteria.
      Compared to admission, at discharge, patients reported a significant decrease in
      Mid-Upper Arm Circumference (MUAC)-from 26.5 cm (+/- 3.6) to 25.9 cm (+/- 3.7) (p
      = 0.016), a reduction in Phase angle (PhA)-from 4.25 degrees  (+/- 1.20) to 4.01
      degrees  (+/- 1.15) (p = 0.005), fat-free mass (FFM)-from 47.5 kg (+/- 9.19) to
      44.9 kg (+/- 9.4) (p = 0.03) and fat-free mass index (FFMI)-from 16.9 kg/m2 (+/-
      2.3) to 15.8 kg/m2 (+/- 2.7) (p = 0.04). Laboratory data showed a reduction of
      albumin-from 29.2 (+/- 5.7) to 28.0 (+/- 5.9) (p = 0.01) and Onodera's PNI- from
      29.1 (+/- 5.6) to 27.6 kg (+/- 5.6) (p = 0.039). At the multivariate linear
      regression analysis, the variables significantly associated with a worsening of
      PhA at discharge are the PhA value at admission and the diagnosis of malnutrition
      according to ESPEN Criteria. Hospitalization leads to significative changes in
      nutritional status. A clinical concern should be raised about the quality of
      hospital food and meal times and on the need for a clinical nutritionist on the
      ward.

PMID- 30191536
TI  - Recovery after cardiac arrest: the brain is the heart of the matter.

PMID- 30191535
TI  - Influence of frailty on anticoagulant prescription and clinical outcomes after 1
      year follow-up in hospitalised older patients with atrial fibrillation.
AB  - Frailty is an important prognostic factor in older adults with cardiovascular
      diseases. We aim to describe the characteristics of elderly hospitalised frail
      patients with non-valvular atrial fibrillation (NVAF) and to assess the influence
      of frailty, along with other functional and health status variables on
      anticoagulation prescription, 1-year all-cause mortality, and the incidence of
      ischemic and bleeding complications. An observational, prospective multicentre
      study was carried out on patients with NVAF over the age of 75, who were admitted
      to the Internal Medicine departments in Spain. A total of 615 patients were
      evaluated (mean age 85.23 +/- 5.16 years, 54.3% females, 48.3% frail). Frail
      patients had higher CHA2DS2-VASc and HAS-BLED scores, more comorbidities and
      worse functional status and cognitive impairment compared to non-frail. During
      hospitalisation, 58 (9.4%) patients died (12.5% frail, 6.6% non-frail, p = 0.01).
      Among the participants discharged, 69.8% received anticoagulants, 13% anti
      platelets only and 16.9% no anti-thrombotics, with no difference by frailty
      status. Frailty is not a predictor of anticoagulant prescription at discharge (OR
      0.93, 95% CI 0.55-1.57), while functional dependency remains significantly
      associated (OR for severe dependency 0.44, 95% CI 0.23-0.82). After the 1-year
      follow-up, frail patients have a higher risk of death (HR 1.99, 95% CI 1.43
      2.76). Among patients taking anticoagulants, the incidence of stroke and major
      bleeding is similar between frailty groups. In our study, frailty is related to
      worse global health status. It has no impact on antithrombotic prescription, nor
      is a predictor of AF complications, even though frail subjects have a higher
      mortality during hospitalisation and after 1-year follow-up.

PMID- 30191537
TI  - Living with Type 2 Diabetes: Patient Commentary in Response to the Paper 'SGLT2
      Inhibitors in Type 2 Diabetes Management: Key Evidence and Implications for
      Clinical Practice'.
AB  - : This article, co-authored by a patient living with type 2 diabetes and a
      diabetes specialist physician, discusses the patient's experience of living with
      type 2 diabetes, including their experience of diagnosis and self-management,
      education and adoption of SGLT2 inhibitors to treat the disease. The physician
      discusses the therapeutic challenges of SGLT2 inhibitors and the importance of
      education. FUNDING: Napp Pharmaceuticals, Ltd.

PMID- 30191539
TI  - Variational mode decomposition based ECG denoising using non-local means and
      wavelet domain filtering.
AB  - This paper presents a novel electrocardiogram (ECG) denoising approach based on
      variational mode decomposition (VMD). This work also incorporates the efficacy of
      the non-local means (NLM) estimation and the discrete wavelet transform (DWT)
      filtering technique. Current ECG denoising methods fail to remove noise from the
      entire frequency range of the ECG signal. To achieve the effective ECG denoising
      goal, the noisy ECG signal is decomposed into narrow-band variational mode
      functions (VMFs) using VMD method. The idea is to filter out noise from these
      narrow-band VMFs. To achieve that, the center frequency information associated
      with each VMFs is used to exclusively divide them into lower- and higher
      frequency signal groups. The higher frequency VMFs were filtered out using DWT
      thresholding technique. The lower frequency VMFs are denoised through NLM
      estimation technique. The non-recursive nature of VMD enables the parallel
      processing of NLM estimation and DWT filtering. The traditional DWT-based
      approaches need large decomposition levels to filter low frequency noises and at
      the same time NLM technique suffers from the rare-patch effect in high-frequency
      region. On the contrary, in the proposed framework both NLM and DWT approaches
      complement each other to overcome their individual ill-effects. The signal
      reconstruction is performed using the denoised high frequency and low frequency
      VMFs. The simulation performed on the MIT-BIH Arrhythmia database shows that the
      proposed method outperforms the existing state-of-the-art ECG denoising
      techniques.

PMID- 30191540
TI  - Recurrent Small Cell Carcinoma of the Uterine Cervix Responding to Combined
      Therapy with Paclitaxel, Cisplatin, and Bevacizumab: A Case Report.
AB  - We report a patient with recurrent refractory small cell carcinoma of the uterine
      cervix, in whom combined therapy with paclitaxel, cisplatin, and bevacizumab
      (TP+Bev) was effective. Small cell cervical carcinoma is a rare malignancy and
      its outcome is reported to be poor. The patient was a 45-year-old woman who
      visited a local hospital with the chief complaint of irregular vaginal bleeding
      and was referred to our department. The results of a smear test and examination
      of a tissue biopsy specimen suggested small cell carcinoma. FIGO stage II A
      disease was diagnosed by MRI and CT. She underwent radical hysterectomy with
      bilateral adnexectomy, and pelvic and para-aortic lymph node dissection. Although
      postoperative adjuvant chemotherapy was performed, local recurrence was found at
      three years after surgery. She received radiation therapy to the whole pelvis,
      bilateral inguinal regions, and site of recurrence. However, multiple liver
      metastases were detected and the tumor was considered to be refractory.
      Subsequently, she received TP+Bev as systemic chemotherapy, after which the local
      recurrence disappeared and the liver metastases became smaller.

PMID- 30191538
TI  - Multiple Aneurysms AnaTomy CHallenge 2018 (MATCH): Phase I: Segmentation.
AB  - PURPOSE: Advanced morphology analysis and image-based hemodynamic simulations are
      increasingly used to assess the rupture risk of intracranial aneurysms (IAs).
      However, the accuracy of those results strongly depends on the quality of the
      vessel wall segmentation. METHODS: To evaluate state-of-the-art segmentation
      approaches, the Multiple Aneurysms AnaTomy CHallenge (MATCH) was announced.
      Participants carried out segmentation in three anonymized 3D DSA datasets (left
      and right anterior, posterior circulation) of a patient harboring five IAs.
      Qualitative and quantitative inter-group comparisons were carried out with
      respect to aneurysm volumes and ostia. Further, over- and undersegmentation were
      evaluated based on highly resolved 2D images. Finally, clinically relevant
      morphological parameters were calculated. RESULTS: Based on the contributions of
      26 participating groups, the findings reveal that no consensus regarding
      segmentation software or underlying algorithms exists. Qualitative similarity of
      the aneurysm representations was obtained. However, inter-group differences
      occurred regarding the luminal surface quality, number of vessel branches
      considered, aneurysm volumes (up to 20%) and ostium surface areas (up to 30%).
      Further, a systematic oversegmentation of the 3D surfaces was observed with a
      difference of approximately 10% to the highly resolved 2D reference image.
      Particularly, the neck of the ruptured aneurysm was overrepresented by all groups
      except for one. Finally, morphology parameters (e.g., undulation and non
      sphericity) varied up to 25%. CONCLUSIONS: MATCH provides an overview of
      segmentation methodologies for IAs and highlights the variability of surface
      reconstruction. Further, the study emphasizes the need for careful processing of
      initial segmentation results for a realistic assessment of clinically relevant
      morphological parameters.

PMID- 30191541
TI  - Impact of Adding Bevacizumab to Paclitaxel + Carboplatin for Platinum-Sensitive
      Recurrent Epithelial Ovarian Cancer: A Propensity Score Matching Analysis.
AB  - PURPOSE: We evaluated whether adding bevacizumab (Bev) to paclitaxel+carboplatin
      (TC) could improve outcomes, especially progression-free survival (PFS), in
      patients with platinum-sensitive recurrent ovarian cancer. PATIENTS AND METHODS:
      Among patients with platinum-sensitive recurrent ovarian cancer treated at our
      hospital from May 2008 to March 2017, PFS was compared between those receiving
      platinum-based chemotherapy or TC+Bev therapy by propensity score matching
      analysis. RESULTS: Nineteen patients received platinum-based chemotherapy and 13
      patients received TC+Bev therapy. PFS (the primary endpoint) was 6.31 months in
      the platinum-based chemotherapy group versus 14.71 months in the TC+Bev group
      (hazard ratio: 0.304; 95% confidence interval: 0.114-0.8121; p=0.01752). The
      safety profile was similar to that expected. CONCLUSION: Adding Bev to TC
      prolonged PFS in patients with platinum-sensitive recurrent ovarian cancer and
      adverse effects were tolerable.

PMID- 30191542
TI  - Effects of Cysteine-stabilized Peptide Fraction of Morinda lucida Leaf on
      Selected Kidney Function Indices in Mice.
AB  - OBJECTIVE: This study evaluated the effect of cysteine-stabilized peptide
      fraction (CSPF) of Morinda lucida leaf on selected kidney function indices in
      mice. METHODS: Sixty mice were assigned into six groups. Group A served as the
      control while groups B, C, D, E and F received 31.25, 61.5, 125, 250, and 500
      mg/kg body weight of CSPF respectively for 7 or 28 days. RESULTS: Administration
      of CSPF for 7 and 28 days caused no significant (p>0.05) alteration in kidney
      body weight ratio, plasma concentrations of the selected electrolytes, urea and
      creatinine at all doses compared to controls. However, plasma uric acid
      concentration was significantly increased (p<0.05) after administration of CSPF
      for 7 days at doses of 125 and 500 mg/kg body weight while it was significantly
      reduced (p<0.05) after administration for 28 days at doses higher than 31.25
      mg/Kg body weight compared to controls. The activities of Ca2+, Mg2+-ATPase and
      Na+, K+-ATPases in the kidney and the histology of the kidney remained unaltered
      (p>0.05) throughout the experimental period compared to controls. CONCLUSION:
      CSPF may adversely affect uric acid metabolism after prolonged administration.

PMID- 30191543
TI  - Detection of Autonomic Nervous System Abnormalities in Diabetic Patients by 24
      hour Ambulatory Blood Pressure Monitoring.
AB  - OBJECTIVE: To determine the relationship between 24-hr blood pressure (BP)
      fluctuations and autonomic nervous system dysfunction in diabetic patients using
      non-invasive ambulatory blood-pressure monitoring (ABPM) system. METHODS: The
      subjects were 39 diabetic patients free of cardiovascular diseases. 24-hr BP was
      monitored by a non-invasive ABPM system. The relationships among 24-hr BP
      fluctuations and various clinical parameters relevant to diabetes and
      hypertension were analyzed. RESULTS: Patients were divided into the diurnal
      hypertension (DH, n=4), diurnal and nocturnal hypertension (DNH, n=9),
      normotension (N, n=14), and nocturnal hypertension (NH, n=12) groups. DH and/or
      NH was observed in 25 (64%) patients: 13 had DH (>=135/85 mmHg), 21 had NH
      (>=120/70 mmHg), and 9 had both. Furthermore, 4 patients with DH but no NH
      (diurnal/nocturnal+/ - ); 9 (+/+); 14 ( - / - ); and 12 ( - /+). The R-R interval
      coefficient of variation on the EKG (CV-RR) was significantly different among the
      groups (N>NH>DNH>DH). CONCLUSION: Autonomic nervous system dysfunction in
      diabetic patients had a negative influence on 24-hr fluctuations in BP.
      Monitoring nighttime hypertension and daily BP variation using ABPM diabetic is a
      potentially useful approach for identifying autonomic nervous system dysfunction
      and associated abnormal BP patterns that cannot be detected by routine check-ups.

PMID- 30191544
TI  - A Young Patient with Emery-Dreifuss Muscular Dystrophy Treated with Endovascular
      Therapy for Cardioembolic Stroke: A Case Report.
AB  - We had a case of Emery-Dreifuss muscular dystrophy (EDMD) in an 18-year-old woman
      who underwent endovascular therapy for a cardioembolic stroke. At 5 years old,
      she showed a high creatine kinase level and atrial fibrillation on
      electrocardiography in our hospital. Finally, she was diagnosed as having EDMD by
      genetic screening that revealed mutations in the LMNA gene (c.810+1G>T). Before
      this event, she received no medications. At 18 years old, she was admitted to our
      hospital>8 hours after the onset of sudden consciousness disturbance.
      Neurological examination on admission revealed consciousness disturbance and
      right hemiplegia. Magnetic resonance imaging revealed a cerebral infarction in
      the left insular cortex and putamen with left internal carotid artery occlusion.
      We performed endovascular therapy and completely recanalized her left internal
      carotid artery. Thereafter, her neurological symptoms improved. She was
      subsequently transferred to a rehabilitation hospital. EDMD is a rare genetic
      muscular disease that mainly presents with contractures, weakness, and cardiac
      conduction abnormalities. Although patients with EDMD are young with low CHADS2
      score, they have a disease-specific cardiovascular pathogenesis caused by a fatal
      risk factor. Therefore, we consider anticoagulant therapy necessary to prevent
      thrombotic events, even if the CHADS2 score is low, in patients with EDMD.

PMID- 30191546
TI  - A Case-control Study on the Risk Factors for Ischemic Colitis.
AB  - OBJECTIVE: Ischemic colitis (IC) is a relatively common acute inflammation
      disorder of the intestine. It was considered to be a disorder of elderly people
      with risk factors for arteriosclerosis; however, a considerable number of young
      people with IC have been reported recently. We performed a case-control study to
      determine the risk factors for IC and compare the risk factors between elderly
      and non-elderly people. METHODS: The study included 209 consecutive patients
      diagnosed with IC between December 2004 and March 2017 at Tokai University
      Hospital. The study also included 209 randomly selected controls in the same
      calendar year so as to match age and sex. Possible risk factors for IC were
      identified and compared between age groups. RESULTS: The mean age of IC group was
      64.9 with 60 males and 115 elderly patients aged 65 or more in each group. On
      multivariable conditional logistic regression analysis, drinking, abdominal
      surgery, hypertension, and malignant diseases were risk factors for IC in all
      ages. In non-elderly patients, only hypertension and laxative/enema use were
      significant factors, while in elderly, abdominal surgery, hypertension, COPD,
      malignant disease and antiplatelet drugs were significant. CONCLUSION: The risk
      factors in elderly people might be quite different from younger ones, while
      hypertension seemed to be a common risk in all ages.

PMID- 30191545
TI  - A Case of Acute Respiratory Distress Syndrome Caused by Waterproofing Spray
      Inhalation.
AB  - We report the case of a 62-year-old man who used approximately one can of
      waterproofing spray in an enclosed room and, then, smoked a cigarette. He
      developed a fever of 39 degrees C with respiratory distress and was transported
      by ambulance to his usual doctor. Since his respiratory state was very severe, he
      was transferred to our hospital. The patient had a smoking habit of 20 cigarettes
      per day for approximately 42 years. Chest computed tomography (CT) on arrival
      showed ground glass opacity (GGO) in the bilateral lungs with emphysematous
      change. We diagnosed the patient with acute respiratory distress syndrome (ARDS)
      because of severe hypoxemia. Based on the symptoms' progress, the cause of ARDS
      was thought to be lung injury due to waterproofing spray inhalation, and
      treatment was accordingly initiated. Several reports have described lung injury
      caused by waterproofing spray inhalation; however, severe cases that progress to
      ARDS are rare. We believe that the aggravation was caused by smoking after
      inhaling the waterproofing spray and pre-existing pulmonary lesions, such as
      emphysema. Education regarding the precautions to be taken when using
      waterproofing spray is necessary.

PMID- 30191547
TI  - Comparison between Endoscopic Treatment and Surgical Drainage of the Pancreatic
      Duct in Chronic Pancreatitis.
AB  - BACKGROUND: Treatment of recurrent chronic obstructive pancreatitis is pancreatic
      duct decompression with endoscopic drainage (endoscopic pancreatic stenting [EPS]
      with extracorporeal shockwave lithotripsy [ESWL]) or surgical drainage. Despite
      the recent popularization of endoscopic drainage, treatment or stent removal is
      difficult in many patients. We compared the efficacy, safety, and medical cost of
      endoscopic and surgical treatments. PATIENTS AND METHODS: We retrospectively
      compared the treatment course and medical cost of hospitalization between 41
      patients who had undergone pancreatic stenting between 2006 and 2010 (EPS group)
      and 10 patients who had undergone surgery for poor control of pancreatitis
      between 2001 and 2005 (surgical drainage group). RESULTS: No intergroup
      differences were observed in causes, symptoms, disease duration, smoking history,
      or endocrine and exocrine functions. The technical success rate was 100% in both
      groups, and pain had improved in all of the patients in both groups. The
      incidences of complications did not differ significantly, and the mortality rate
      was 0% in both groups. The rehospitalization rate was significantly higher in the
      EPS group (78%) than that in the surgical drainage group (20%; P<0.01). This was
      considered attributable to rehospitalization for stent replacement. The effects
      to improve endocrine and exocrine functions were not different between the two
      groups before and after treatment, and the current condition was maintained in
      80% or more of the patients. For the entire EPS group, the mean hospitalization
      period was 18 days and the mean medical cost of hospitalization was 2,133,330
      yen. For the entire surgical drainage group, the mean hospitalization period was
      23 days and the mean medical cost of hospitalization was 2,246,548 yen, thus
      indicating no significant differences between the two groups. CONCLUSIONS:
      Although both endoscopic and surgical treatments achieved high symptom control
      and safety rates, re-hospitalization is required for stent replacement, which
      leads to poor cost-effectiveness, particularly in patients in whom stent removal
      is difficult. Endoscopic treatment for severe pancreatic duct stenosis will need
      to be advanced and evaluated in the future.

PMID- 30191548
TI  - Using Artificial DNA Sequence to Suppress Non-specific Bindings in Crude Nuclear
      Extract During Surface Plasmon Resonance Assay.
AB  - OBJECTIVE: Surface plasmon resonance (SPR) has been extensively used to
      characterize the interactions between molecules in terms of their binding
      specificity, affinity, and kinetics. Practical procedures, however, for
      measurement of the protein-DNA association in crude nuclear extract are yet to be
      defined. METHODS: Crude nuclear extract was obtained from MCF-7 cells or
      recombinant estrogen receptor alpha (ERalpha) was used for analysis. To suppress
      signal from non-specific bindings in SPR assay using Biacore, DNA fragments with
      minimal protein binding activity were identified in a database for transcription
      factors and included in the study. RESULTS: It is known that when analytes were
      purified transcription factors, the dissociation curves in Biacore sensorgrams
      exhibit exponential tendency. Based on statistical analysis, the dissociation
      phase between the ERalpha complex from crude nuclear extract and DNA
      oligonucleotides could be fitted exponentially. Following extrapolation of the
      dissociation phase, theoretical amount of bound antibodies could be estimated and
      compared for significant difference. CONCLUSION: Our procedures made SPR
      technique such as Biacore a practical technique for measurement of protein-DNA
      associations in crude nuclear extract with reproducible and reliable results.

PMID- 30191549
TI  - Rational design of a hexameric protein assembly stabilized by metal chelation.
AB  - Protein-based self-assembled nanostructures hold tremendous promise as smart
      materials. One strategy to control the assembly of individual protein modules
      takes advantage of the directionality and high affinity bonding afforded by metal
      chelation. Here, we describe the use of 2,2'-bipyridine units (Bpy) as side
      chains to template the assembly of large structures (MW approx. 35 000 Da) in a
      metal-dependent manner. The structures are trimers of independently folded 3
      helix bundles, and are held together by 2 Me(Bpy)3 complexes. The assemblies are
      stable to thermal denaturation, and are more than 90% helical at 90 degrees C.
      Circular dichroism spectroscopy shows that one of the 2 possible (Bpy)3
      enantiomers is favored over the other. Because of the sequence pliability of the
      starting peptides, these constructs could find use to organize functional groups
      at controlled positions within a supramolecular assembly.

PMID- 30191550
TI  - "Over the Internet" sale of prescription-level topical corticosteroids and
      dilemma of dermatologists.

PMID- 30191551
TI  - Storage stability of electrospun pure gelatin stabilized with EDC/Sulfo-NHS.
AB  - With the rapid development of biomimetic polymers for cell-based assays and
      tissue engineering, crosslinking electrospun nanofibrous biopolymer constructs is
      of great importance for achieving sustainable and efficient three-dimensional
      scaffold constructs. Uncrosslinked electrospun gelatin nanofibrous constructs
      immediately and completely dissolved in aqueous solutions due to their aqueous
      solubility and poor storage stability. Here, a novel and versatile approach for
      the fabrication and crosslinking of electrospun gelatin construct with tunable
      porosity and high aspect ratio nanofibers is presented. Uncrosslinked electrospun
      gelatin/genipin nanofibrous and pure gelatin nanofibrous constructs exhibited
      smooth surfaces that were well-defined, with a diameter in the range of 448 +/-
      364 nm and 257 +/- 57 nm, respectively. Dehydrothermal, genipin-EDC/Sulfo-NHS,
      and EDC/Sulfo-NHS crosslinking approaches were examined to achieve insoluble
      gelatin nanofibrous constructs that were suitable for cell-based assays.
      Mechanical characterization demonstrated that the pure gelatin nanofibrous
      construct crosslinked via EDC/Sulfo-NHS exhibited an increased mechanical
      strength and stiffness and showed no dissolution in aqueous solutions and
      retained its fiber morphology. An excellent 1 month storage stability was
      demonstrated at 22, 4, -20, and -80 degrees C (dehydrated) and at 4 degrees C
      (hydrated). The as-crosslinked gelatin nanofibrous construct was highly
      biocompatible (90% cell viability), as demonstrated by the promoted proliferation
      of PC12 cells.

PMID- 30191552
TI  - A study comparing the practice of Australian maternity care providers in relation
      to maternal immunisation.
AB  - BACKGROUND: Women's decisions regarding vaccination during pregnancy are heavily
      influenced by maternity care provider (MCP) recommendations. Understanding why
      MCPs may not recommend vaccination is central to improving vaccination rates.
      AIMS: To examine the knowledge, attitudes and practice of Australian MCPs to
      maternal vaccination. METHODS: We surveyed obstetricians, midwives and general
      practitioners (GPs) between September and November 2016. Providers were asked
      about their knowledge and current practice, and about their perceived roles in
      discussing and administering maternal vaccinations. RESULTS: Eight hundred and
      seventy surveys were completed. Each MCP group believed they had the primary
      responsibility for discussing vaccinations but all groups perceived GPs as
      primarily responsible for administering vaccines. More midwives had concerns
      about safety (21/129, 16%) than obstetricians (9/359, 3%) and GPs (7/326, 2%) (P
      < 0.001). Overall, 83% of MCPs recommended diphtheria-tetanus-acellular pertussis
      vaccination (dTpa) and 78% inactivated influenza vaccination (IIV) according to
      guidelines, with no differences between groups. Overall 77% provided dTpa onsite
      (GPs 99%, midwives 70%, obstetricians 60%, P < 0.001) and 71% provided IIV (GPs
      99%, midwives 48%, obstetricians 54%, P < 0.001). Factors associated with
      recommending vaccination in accordance with guidelines and providing vaccination
      onsite were similar across groups: personal history of vaccination, confidence in
      vaccine knowledge, and awareness of recommendations for and belief in the safety
      of maternal dTpa. CONCLUSIONS: Among MCPs, the rates of recommending and
      providing maternal vaccination were higher than previously reported. Further
      improvements might be expected with increased awareness of guidelines, further
      education around vaccine safety, and by changing perceptions of the role of
      obstetricians and midwives in providing maternal vaccinations.

PMID- 30191553
TI  - Erratum.

PMID- 30191555
TI  - Aggressive primary cutaneous CD30+ lymphoproliferative disorder in an organ
      transplant recipient in sustained complete remission with brentuximab vedotin.

PMID- 30191556
TI  - Nodular fasciitis, a forgotten entity.
AB  - BACKGROUND: Nodular fasciitis is a benign pseudosarcomatous, self-limited, and
      reactive process. Based on its clinical and histological features - a fast
      growing, solitary tumor with high cellularity and mitotic count - nodular
      fasciitis is considered to be a benign mimic of sarcoma. METHODS: We present four
      cases of nodular fasciitis and a review of the literature. RESULTS: The cases we
      present were initially misdiagnosed as sarcoma; two as dermatofibrosarcoma
      protuberans, one as atypical fibroxanthoma, and one as leiomyosarcoma.
      CONCLUSION: Awareness of this entity among dermatologists is important as
      misdiagnosis may lead to unnecessary treatments associated with increased
      morbidity.

PMID- 30191557
TI  - Cytomegalovirus ulcers following radiotherapy for a Marjolin ulcer in a renal
      transplant recipient.
AB  - Cytomegalovirus (CMV) infection represents a major cause of morbidity and
      mortality in immunocompromised hosts. Skin ulceration is a rare manifestation of
      tissue-invasive disease, with the anogenital region being the most typical site
      of involvement. We present a case of CMV ulceration on the right leg occurring 16
      years following renal transplantation and 1 year after adjuvant radiotherapy for
      a Marjolin ulcer at this site. We suggest radiotherapy may provide a mechanism
      for local reactivation of the virus in the skin of seropositive patients.

PMID- 30191558
TI  - Zika virus exposure in pregnancy and its association with newborn visual
      anomalies and hearing loss.
AB  - Exposure to Zika virus (ZIKV) in pregnancy leads to a spectrum of congenital
      effects in the newborn. Recent studies have begun to evaluate the impact of ZIKV
      during pregnancy. Among 39 relevant studies, nine were related specifically to
      clinical studies of ophthalmologic disorders and one was related to hearing loss
      impairment; most of these studies were case reports and case series reports.
      Importantly, congenital toxoplasmosis was ruled out in all studies. The data show
      that, in addition to microcephaly, ZIKV exposure in pregnancy may result in
      subtle ocular impairments in the newborn. The most common anomalies are macular
      pigment mottling and/or chorioretinal atrophy, and optic nerve disorders.
      Sensorineural hearing loss has also been noted in 5.8% of infants with
      microcephaly. The effects of ZIKV infection during pregnancy are potentially
      devastating to the fetus and newborn. Although microcephaly is an important
      signal, the current information emphasizes the importance of ocular and auditory
      screenings, otherwise sight and hearing anomalies may be underestimated.
      Healthcare providers should fully understand the spectrum of anomalies related to
      ZIKV exposure in pregnancy in order to counsel pregnant women living in high-risk
      areas, in addition to those wanting to become pregnant.

PMID- 30191559
TI  - Transplanted enteric neural stem cells integrate within the developing chick
      spinal cord: implications for spinal cord repair.
AB  - Spinal cord injury (SCI) causes paralysis, multisystem impairment and reduced
      life expectancy, as yet with no cure. Stem cell therapy can potentially replace
      lost neurons, promote axonal regeneration and limit scar formation, but an
      optimal stem cell source has yet to be found. Enteric neural stem cells (ENSC)
      isolated from the enteric nervous system (ENS) of the gastrointestinal (GI) tract
      are an attractive source. Here, we used the chick embryo to assess the potential
      of ENSC to integrate within the developing spinal cord. In vitro, isolated ENSC
      formed extensive cell connections when co-cultured with spinal cord (SC)-derived
      cells. Further, qRT-PCR analysis revealed the presence of TuJ1+ neurons, S100+
      glia and Sox10+ stem cells within ENSC neurospheres, as well as expression of key
      neuronal subtype genes, at levels comparable to SC tissue. Following ENSC
      transplantation to an ablated region of chick embryo SC, donor neurons were found
      up to 12 days later. These neurons formed bridging connections within the SC
      injury zone, aligned along the anterior/posterior axis, and were immunopositive
      for TuJ1. These data provide early proof of principle support for the use of
      ENSCs for SCI, and encourage further research into their potential for repair.

PMID- 30191560
TI  - Activation of melanoblasts and melanocytes after treatment with monochromatic
      excimer light and narrowband-ultraviolet B of skin of vitiligo patients.
AB  - BACKGROUND: Vitiligo is a hypopigmentation disease characterized by achromatic or
      hypochromatic macules in several sites of human skin. Although monochromatic
      excimer light (MEL) and narrowband-ultraviolet B (NB-UVB) have recently been used
      for efficacious treatment of vitiligo, the repigmentation process and role of
      melanocytes/melanoblasts are not well known. METHODS: White macules of 28
      vitiligo patients were repeatedly exposed with MEL/NB-UVB. After the exposures,
      punch biopsies of the center and edge of the lesional skin in addition to normal
      skin were fixed and processed to dopa and combined dopa-premelanin reactions.
      Melanocytes positive to the dopa reaction and melanoblasts/melanocytes positive
      to the combined dopa-premelanin reaction were surveyed. RESULTS: Two
      repigmentation patterns were observed; one was "marginal" and the other was
      "perifollicular." Although the frequency of the former pattern was much lower
      than that of the latter pattern, no differences were observed in average
      percentage of repigmentation and the number of melanocytes and melanoblasts
      observed at the center and edge of the lesional epidermis. CONCLUSIONS: These
      results suggest that exposures with MEL/NB-UVB induce the marginal or
      perifollicular repigmentation pattern in the white macules, though the two
      patterns produce no differences in the distribution and density of
      melanoblasts/melanocytes in the lesional epidermis.

PMID- 30191562
TI  - World Congress on Cancers of the Skin(r) 2018, International Convention Centre,
      Sydney, 15-18 August 2018.

PMID- 30191561
TI  - Systemic treatments for alopecia areata: A systematic review.
AB  - A range of systemic treatments are used for alopecia areata with variable
      evidence supporting efficacy. In this systematic review, we evaluated the
      evidence surrounding systemic treatments for alopecia areata, alopecia totalis
      and alopecia universalis. A systematic search was conducted of the peer-reviewed
      literature published between 1946 and March 2018 via Medline, Embase, Amed, the
      Cochrane Central Register of Controlled Trials, PsychINFO and Lilacs. All
      randomised controlled trials (RCTs) that evaluated the effectiveness of systemic
      treatments for individuals with alopecia areata, totalis or universalis were
      included. Sixteen studies were included with a total of 768 participants. We
      found eight placebo-controlled RCTs, three RCTs comparing two systemic treatments
      and five RCTs comparing three treatments. A total of 15 different systemic
      therapies were investigated. The most frequently investigated therapy was oral
      prednisolone pulse therapy and oral inosiplex. There was significant variability
      in the definition of treatment success. No study evaluated the impact of
      pharmacotherapy on quality of life using complete quantitative quality of life
      instruments. Adverse events were reported in 13 studies and were corticosteroid
      related or otherwise well tolerated. Relapse rates were considerable in the four
      studies that reported this outcome. There is currently no specific systemic
      therapy that is supported by robust body of evidence from RCTs. The current
      evidence suggests efficacy of oral prednisolone pulse therapy and oral inosiplex.
      Evidence does not support the use of oral zinc sulphate, alefacept and
      efalizumab. Future RCTs should be adequately powered and employ clearly defined
      clinical response endpoints to allow future meta-analyses.

PMID- 30191563
TI  - Bone marrow harvest in donors with anaemia.
AB  - BACKGROUND: Bone marrow harvest (BMH) for haematopoietic stem cell
      transplantation is a well-established procedure. The guidelines of World Marrow
      Donor Association provide information on donor selection. However, some of the
      guidelines regarding donors with anaemia prior to harvest lack in supporting data
      from clinical studies. With this study, we aimed to provide such data. MATERIAL
      AND METHODS: In this retrospective, single-centre study, we analysed the
      interplay between haemoglobin levels and BMH and BMH impact on haemoglobin levels
      in a cohort of 149 unrelated BM donors, including 13 subjects with mild anaemia.
      RESULTS: The BMH led to significantly lower decrease in haemoglobin levels in
      donors with anaemia than in control group (1.79 g/dl vs. 2.56 g/dl, P < 0.0001).
      The following parameters: BMH volume (ml), BMH volume/donor body weight (ml/kg),
      total nucleated cells (TNC) in product (*108 ) and TNC/kg recipient body weight
      in product (*108 /kg) did not differ significantly between those two analysed
      groups (P > 0.05). Median BM volume harvested from anaemic donors was 16.34
      ml/kg; none of them required blood transfusion after BMH. CONCLUSION: Mild
      anaemia prior to BMH does not significantly impact the collection results. The
      BMH is safe and feasible in donors with mild anaemia.

PMID- 30191564
TI  - Sustainable control strategies for plant protection and food packaging sectors by
      natural substances and novel nanotechnological approaches.
AB  - An overview is provided of the current technological strategies (also at the
      nanoscale level) recently involved in plant and/or food protection. In addition,
      the potential use of natural and sustainable substances, instead of traditional
      synthesized molecules or chemical-based compounds, is addressed both with respect
      to packaging systems and novel pesticide formulations. In this context,
      nanotechnological approaches represent promising strategies for the entire
      agriculture industry chain, from the field to consumers. Traditional plant
      protection strategies are often insufficient and the application of chemical
      based pesticides has negative effects on animals, humans and the environment.
      Novel greener tools could represent efficient alternatives for the management of
      plant diseases using promising strategies; the use of nanotechnologies allows the
      promotion of the more efficient assembly and subsequent release of
      environmentally sustainable active principles, limiting the use of chemicals in
      terms of economic losses. At the same time, new sustainable, antimicrobial and
      antioxidant systems have been rapidly promoted and investigated in the food
      packaging sector as a valid eco-friendly possibility for improving the safety and
      quality of food products and reducing and/or limiting the environmental impact
      with respect to traditional materials. Together, the scientific community and the
      growing interest of consumers have promoted the development of new edible and eco
      friendly packaging that reduces waste and any environmental impact. In this
      context, the aim is to provide evidence of the usefulness of strategies aiming to
      limit agrochemicals, as well as the potential of nanomaterials, in sustainable
      plant and food protection for agriculture management and the packaging sector.
      (c) 2018 Society of Chemical Industry.

PMID- 30191565
TI  - Quality evaluation and traceability of Bletilla striata by fluorescence
      fingerprint coupled with multiway chemometrics analysis.
AB  - BACKGROUND: Traditional methods of evaluating herbs were mainly based on
      chromatographic techniques. They usually included tedious sample preparation
      procedures, taking tens of minutes to hours, and consume solvents as well as
      standards for external calibration. In this paper, the feasibility of employing a
      fluorescence fingerprint coupled with multi-way chemometrics analysis for quality
      evaluation and traceability of Bletilla striata were investigated. RESULTS:
      Relative concentrations of four markers presented in B. striata were determined
      by using a four-component self-weighted alternating trilinear decomposition
      (SWATLD) model. These markers could be applied to accurate classification and
      quality control of B. striata samples from different regions. Furthermore,
      multiway principal component analysis, multilinear partial least squares
      discriminant analysis (PLS-DA), unfolded PLS-DA, and SWATLD-PLS-DA models were
      applied to classify the B. striata samples according to their geographic origins.
      Consistent results were obtained showing that B. striata samples could be
      successfully grouped based on their geographical origins and quality. CONCLUSION:
      Our results revealed that the method developed can be used for quality evaluation
      and traceability of B. striata. Compared with the chromatographic methods, the
      method employed in this study was more convenient, simpler, and more sensitive.
      (c) 2018 Society of Chemical Industry.

PMID- 30191566
TI  - The effect of statins on the recurrence rate of atrial fibrillation after
      catheter ablation: A meta-analysis.
AB  - BACKGROUND: To more precisely evaluate the effect of statins on patients with
      atrial fibrillation (AF) after catheter ablation, we performed a meta-analysis of
      published studies. METHODS: We searched PubMed, EMBASE, and Cochrane Library for
      all relevant published articles from the date of inception to April 2017. Odds
      ratios (OR) and 95% confidence intervals (CIs) were then calculated and pooled
      using a random-effects model. Statistical heterogeneity was evaluated using the
      I2 statistic. RESULTS: Nine studies with a total of 1,607 patients were included
      in the analysis. Overall, statins did not reduce the recurrence rate of AF after
      catheter ablation (OR 0.81, 95% CI 0.59-1.10, P = 0.18). However, in the subgroup
      analysis, the randomized control trial (RCT) group significantly reduced the
      recurrence of AF (OR 0.47, 95% CI 0.30-0.75, P = 0.001). Conversely, the
      retrospective cohort study subgroup also had a negative result (OR 1.03, 95% CI
      0.78-1.36, P = 0.82). CONCLUSIONS: Statin use was associated with a significantly
      lower AF recurrence rate in RCTs but not in the whole analysis and the
      observational studies.

PMID- 30191554
TI  - Interventions for preventing falls in older people in care facilities and
      hospitals.
AB  - BACKGROUND: Falls in care facilities and hospitals are common events that cause
      considerable morbidity and mortality for older people. This is an update of a
      review first published in 2010 and updated in 2012. OBJECTIVES: To assess the
      effects of interventions designed to reduce the incidence of falls in older
      people in care facilities and hospitals. SEARCH METHODS: We searched the Cochrane
      Bone, Joint and Muscle Trauma Group Specialised Register (August 2017); Cochrane
      Central Register of Controlled Trials (2017, Issue 8); and MEDLINE, Embase,
      CINAHL and trial registers to August 2017. SELECTION CRITERIA: Randomised
      controlled trials of interventions for preventing falls in older people in
      residential or nursing care facilities, or hospitals. DATA COLLECTION AND
      ANALYSIS: One review author screened abstracts; two review authors screened full
      text articles for inclusion. Two review authors independently performed study
      selection, 'Risk of bias' assessment and data extraction. We calculated rate
      ratios (RaR) with 95% confidence intervals (CIs) for rate of falls and risk
      ratios (RRs) and 95% CIs for outcomes such as risk of falling (number of people
      falling). We pooled results where appropriate. We used GRADE to assess the
      quality of evidence. MAIN RESULTS: Thirty-five new trials (77,869 participants)
      were included in this update. Overall, we included 95 trials (138,164
      participants), 71 (40,374 participants; mean age 84 years; 75% women) in care
      facilities and 24 (97,790 participants; mean age 78 years; 52% women) in
      hospitals. The majority of trials were at high risk of bias in one or more
      domains, mostly relating to lack of blinding. With few exceptions, the quality of
      evidence for individual interventions in either setting was generally rated as
      low or very low. Risk of fracture and adverse events were generally poorly
      reported and, where reported, the evidence was very low-quality, which means that
      we are uncertain of the estimates. Only the falls outcomes for the main
      comparisons are reported here.Care facilitiesSeventeen trials compared exercise
      with control (typically usual care alone). We are uncertain of the effect of
      exercise on rate of falls (RaR 0.93, 95% CI 0.72 to 1.20; 2002 participants, 10
      studies; I2 = 76%; very low-quality evidence). Exercise may make little or no
      difference to the risk of falling (RR 1.02, 95% CI 0.88 to 1.18; 2090
      participants, 10 studies; I2 = 23%; low-quality evidence).There is low-quality
      evidence that general medication review (tested in 12 trials) may make little or
      no difference to the rate of falls (RaR 0.93, 95% CI 0.64 to 1.35; 2409
      participants, 6 studies; I2 = 93%) or the risk of falling (RR 0.93, 95% CI 0.80
      to 1.09; 5139 participants, 6 studies; I2 = 48%).There is moderate-quality
      evidence that vitamin D supplementation (4512 participants, 4 studies) probably
      reduces the rate of falls (RaR 0.72, 95% CI 0.55 to 0.95; I2 = 62%), but probably
      makes little or no difference to the risk of falling (RR 0.92, 95% CI 0.76 to
      1.12; I2 = 42%). The population included in these studies had low vitamin D
      levels.Multifactorial interventions were tested in 13 trials. We are uncertain of
      the effect of multifactorial interventions on the rate of falls (RaR 0.88, 95% CI
      0.66 to 1.18; 3439 participants, 10 studies; I2 = 84%; very low-quality
      evidence). They may make little or no difference to the risk of falling (RR 0.92,
      95% CI 0.81 to 1.05; 3153 participants, 9 studies; I2 = 42%; low-quality
      evidence).HospitalsThree trials tested the effect of additional physiotherapy
      (supervised exercises) in rehabilitation wards (subacute setting). The very low
      quality evidence means we are uncertain of the effect of additional physiotherapy
      on the rate of falls (RaR 0.59, 95% CI 0.26 to 1.34; 215 participants, 2 studies;
      I2 = 0%), or whether it reduces the risk of falling (RR 0.36, 95% CI 0.14 to
      0.93; 83 participants, 2 studies; I2 = 0%).We are uncertain of the effects of bed
      and chair sensor alarms in hospitals, tested in two trials (28,649 participants)
      on rate of falls (RaR 0.60, 95% CI 0.27 to 1.34; I2 = 0%; very low-quality
      evidence) or risk of falling (RR 0.93, 95% CI 0.38 to 2.24; I2 = 0%; very low
      quality evidence).Multifactorial interventions in hospitals may reduce rate of
      falls in hospitals (RaR 0.80, 95% CI 0.64 to 1.01; 44,664 participants, 5
      studies; I2 = 52%). A subgroup analysis by setting suggests the reduction may be
      more likely in a subacute setting (RaR 0.67, 95% CI 0.54 to 0.83; 3747
      participants, 2 studies; I2 = 0%; low-quality evidence). We are uncertain of the
      effect of multifactorial interventions on the risk of falling (RR 0.82, 95% CI
      0.62 to 1.09; 39,889 participants; 3 studies; I2 = 0%; very low-quality
      evidence). AUTHORS' CONCLUSIONS: In care facilities: we are uncertain of the
      effect of exercise on rate of falls and it may make little or no difference to
      the risk of falling. General medication review may make little or no difference
      to the rate of falls or risk of falling. Vitamin D supplementation probably
      reduces the rate of falls but not risk of falling. We are uncertain of the effect
      of multifactorial interventions on the rate of falls; they may make little or no
      difference to the risk of falling.In hospitals: we are uncertain of the effect of
      additional physiotherapy on the rate of falls or whether it reduces the risk of
      falling. We are uncertain of the effect of providing bed sensor alarms on the
      rate of falls or risk of falling. Multifactorial interventions may reduce rate of
      falls, although subgroup analysis suggests this may apply mostly to a subacute
      setting; we are uncertain of the effect of these interventions on risk of
      falling.

PMID- 30191567
TI  - Impact of polyphenols on the headspace concentration of aroma compounds in apple
      cider.
AB  - BACKGROUND: To study the effect of polyphenols on the release of aroma compounds
      in apple cider, the impact of (-)-epicatechin, hydrocaffeic acid and phloridzin
      on volatility of 12 typical aroma compounds was investigated by headspace solid
      phase microextraction and gas chromatography-mass spectrometry. RESULTS: Analysis
      of variance results showed that increased concentrations of the phenolic
      compounds significantly affected the headspace concentration of most aroma
      compounds. The three polyphenols induced a volatility decrease for the majority
      of hydrophobic aroma compounds, while they exhibited an opposite behavior by
      salting out some hydrophilic alcohols. (-)-Epicatechin and hydrocaffeic acid
      showed a higher retention effect on most hydrophobic aroma compounds than
      phloridzin did. CONCLUSION: This study showed that the polyphenols had varying
      effects on aroma compound volatility in apple cider. The physicochemical
      characteristics and spatial conformation of polyphenols and aroma compounds
      influenced the magnitude of aroma-polyphenol interaction in apple cider.
      Understanding the effects of polyphenols on aroma release can improve the
      prediction of aroma profiles through chemical analysis, which assists cidermakers
      in improving the aroma quality of apple cider. (c) 2018 Society of Chemical
      Industry.

PMID- 30191568
TI  - Misdiagnosis of mycorrhizas and inappropriate recycling of data can lead to false
      conclusions.
AB  - We draw attention to a worrying trend for the uncritical use of 'recycled'
      mycorrhizal data to compile host species lists that include obvious errors or
      undertake risky analyses that correlate mycorrhizal colonisation levels with
      environmental or physiological factors despite inherent limitations in datasets.
      We are not suggesting that all meta-studies are wrong, only that more care should
      be taken to resolve what can safely be done with recycled mycorrhizal data in the
      future. We also recommend that mycorrhizal species lists should be checked
      against standard references since the majority of EM hosts and NM plant belong to
      families that are well resolved. However, additional research is required in
      cases where plant families have multiple root types within genera or occur in
      habitats where mycorrhizal associations are often suppressed (see Brundrett &
      Tedersoo, 2018). We hope that the mycorrhizal science community will work
      together more closely in the future to develop and enforce standards for
      mycorrhizal diagnosis and to share carefully corrected datasets for realistic
      meta-studies.

PMID- 30191569
TI  - The evolution of surgical approach for esophageal cancer.
AB  - Esophageal surgery for esophageal cancer has been performed for over a century
      now. Minimally invasive esophagectomy (MIE) was first described in 1992, and it
      is now a standard approach in many countries. However, MIE is technically
      difficult and requires a long learning curve. It takes >100 cases to train for
      MIE with gastric tube reconstruction with an intrathoracic anastomosis. A
      possible option to overcome several challenges of MIE might be the use of a
      robotic system. A robot-assisted MIE was first described in 2005, and long-term
      results have shown its feasibility and safety. Over the years, different
      approaches for esophagectomy have been established. Our review discusses these
      developments and recent literature on open, minimally invasive and robotic
      esophageal surgery.

PMID- 30191570
TI  - Priorities for science to overcome hurdles thwarting the full promise of the
      'digital agriculture' revolution.
AB  - The world needs to produce more food, more sustainably, on a planet with scarce
      resources and under changing climate. The advancement of technologies, computing
      power and analytics offers the possibility that 'digitalisation of agriculture'
      can provide new solutions to these complex challenges. The role of science is to
      evidence and support the design and use of digital technologies to realise these
      beneficial outcomes and avoid unintended consequences. This requires
      consideration of data governance design to enable the benefits of digital
      agriculture to be shared equitably and how digital agriculture could change
      agricultural business models; that is, farm structures, the value chain and
      stakeholder roles, networks and power relations, and governance. We argue that
      this requires transdisciplinary research (at pace), including explicit
      consideration of the aforementioned socio-ethical issues, data governance and
      business models, alongside addressing technical issues, as we now have to
      simultaneously deal with multiple interacting outcomes in complex technical,
      social, economic and governance systems. The exciting prospect is that
      digitalisation of science can enable this new, and more effective, way of
      working. The question then becomes: how can we effectively accelerate this shift
      to a new way of working in agricultural science? As well as identifying key
      research areas, we suggest organisational changes will be required: new research
      business models, agile project management; new skills and capabilities; and
      collaborations with new partners to develop 'technology ecosystems'. (c) 2018 The
      Authors. Journal of The Science of Food and Agriculture published by John Wiley &
      Sons Ltd on behalf of Society of Chemical Industry.

PMID- 30191572
TI  - A case of bidirectional conduction block within the superior vena cava induced by
      cryoballoon pulmonary vein isolation.
AB  - A 53-year-old male underwent a pulmonary vein isolation (PVI) of atrial
      fibrillation (AF) with a second-generation cryoballoon (CB). Although the patient
      maintained sinus rhythm after the PVI, a superior vena cava (SVC) fibrillation
      was recorded by a circular-multipolar-electrode catheter positioned inside the
      SVC that suggested conduction block between the right atrium (RA)-SVC connection.
      An adenosine triphosphate intravenous injection induced a dormant reconnection of
      the SVC myocardial sleeve and converted sinus rhythm to an AF rhythm. This case
      demonstrated that a CB application for the isolation of a right superior
      pulmonary vein could induce an electrical conduction block between the RA-SVC
      connection.

PMID- 30191571
TI  - A framework for performance characterization of energy-resolving photon-counting
      detectors.
AB  - PURPOSE: Photon-counting, energy-resolving detectors are subject to intense
      research interest, and there is a need for a general framework for performance
      assessment of these detectors. The commonly used linear-systems theory framework,
      which measures detector performance in terms of noise-equivalent quanta (NEQ) and
      detective quantum efficiency (DQE) is widely used for characterizing conventional
      x-ray detectors but does not take energy-resolving capabilities into account. The
      purpose of this work is to extend this framework to encompass energy-resolving
      photon-counting detectors and elucidate how the imperfect energy response and
      other imperfections in real-world detectors affect imaging performance, both for
      feature detection and for material quantification tasks. METHOD: We generalize
      NEQ and DQE to matrix-valued quantities as functions of spatial frequency, and
      show how these matrices can be calculated from simple Monte Carlo simulations. To
      demonstrate how the new metrics can be interpreted, we compute them for
      simplified models of fluorescence and Compton scatter in a photon-counting
      detector and for a Monte Carlo model of a CdTe detector with  RESULTS: Our
      results show that the ideal-linear-observer performance for any detection or
      material quantification task can be calculated from the proposed generalized NEQ
      and DQE metrics. We also demonstrate that the proposed NEQ metric is closely
      related to a generalized version of the Cramer-Rao lower bound commonly used for
      assessing material quantification performance. Off-diagonal elements in the NEQ
      and DQE matrices are shown to be related to loss of energy information due to
      imperfect energy resolution. The Monte Carlo model of the CdTe detector predicts
      a zero-frequency dose efficiency relative to an ideal detector of 0.86 and 0.65
      for detecting water and bone, respectively. When the task instead is to quantify
      these materials, the corresponding values are 0.34 for water and 0.26 for bone.
      CONCLUSIONS: We have developed a framework for assessing the performance of
      photon-counting energy-resolving detectors and shown that the matrix-valued NEQ
      and DQE metrics contain sufficient information for calculating the dose
      efficiency for both detection and quantification tasks, the task having any
      spatial and energy dependence. This framework will be beneficial for the
      development and optimization of photon-counting x-ray detectors.

PMID- 30191574
TI  - Carotenoids retention in biofortified yellow cassava processed with traditional
      African methods.
AB  - BACKGROUND: Biofortified yellow cassava is being cultivated in countries with
      high cassava consumption to improve its population's vitamin A status. The
      carotenoid retention in biofortified cassava when processed as boiled, fufu, and
      chikwangue was evaluated in this study. Commercial biofortified varieties Kindisa
      and Vuvu and the experimental genotypes MVZ2011B/360 and MVZ2012/044 were used.
      Fresh cassava roots were processed as boiled, fufu, and chikwangue. Provitamin A
      carotenoids (pVACs) content of fresh and processed cassava was measured by high
      performance liquid chromatography, and total carotenoids was measured by
      spectrophotometer. RESULTS: pVACs content of fresh peeled cassava was 1.79-6.65
      ug g-1 on a fresh weight basis, whereas in boiled cassava, fufu, and chikwangue
      the pVACs content was 1.71-6.91 ug g-1 , 0.04-0.37 ug g-1 , and 0.52-1.75 ug g-1
      respectively. True retention of carotenoids after cooking was 93.2-96.8%, 0.8
      3.1%, and 4.0-18.1% for boiled cassava, fufu, and chikwangue respectively.
      Significant total carotenoids loss was observed during storage. CONCLUSION: The
      results indicated that biofortified boiled cassava could be an effective food
      product to improve pVACs intake in areas where vitamin A deficiency exists, and
      processing of chikwangue and fufu should be improved before promoting
      biofortified cassava in vitamin-A-deficient areas with high cassava consumption.
      (c) 2018 The Authors. Journal of the Science of Food and Agriculture published by
      John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

PMID- 30191575
TI  - Rapid, simultaneous, and in situ authentication and quality assessment of intact
      bell peppers using near-infrared spectroscopy technology.
AB  - BACKGROUND: The ability of near-infrared (NIR) spectroscopy to authenticate
      individual bell peppers as a function of the growing system (outdoor or
      greenhouse) was tested using partial least squares discriminant analysis. Bell
      peppers grown outdoors (130 samples) or in a greenhouse (264 samples) during the
      2015 and 2016 seasons were selected for this purpose and analysed using a
      portable, handheld, microelectromechanical system (MEMS) instrument MicroPhazir
      (spectral range 1600-2400 nm), working in reflectance. Subsequently, the
      potential of NIR spectroscopy as a non-destructive sensor for in situ quality
      (dry matter and soluble solid content) measurements, was investigated. RESULTS:
      The models correctly classified 89.73% and 88.00% of the samples by growing
      system, when trained with unbalanced and balanced sets respectively, mainly due
      to the differences in physical-chemical attributes between bell peppers
      cultivated in the two growing systems. Separate classification models for bell
      peppers grouped by ripeness (judged by the colour), allowed the classification of
      88.28-91.37% of the samples correctly. The standard error of cross-validation
      values for the quantitative models were 0.66% fresh weight and 0.75  degrees Brix
      for dry matter and soluble solid content, respectively. CONCLUSIONS: The results
      showed that NIR spectroscopy can be used successfully for predicting the growing
      systems used in bell pepper production, which is of particular value to guarantee
      the authentication of outdoor-grown peppers. Additionally, the results showed
      that NIR spectroscopy can be used simultaneously as a rapid preliminary screening
      technique to measure quality. (c) 2018 Society of Chemical Industry.

PMID- 30191573
TI  - Theoretical and experimental analysis of photon counting detector CT for proton
      stopping power prediction.
AB  - PURPOSE: Photon counting detectors (PCDs) are being introduced in advanced x-ray
      computed tomography (CT) scanners. From a single PCD-CT acquisition, multiple
      images can be reconstructed, each based on only a part of the original x-ray
      spectrum. In this study, we investigated whether PCD-CT can be used to estimate
      stopping power ratios (SPRs) for proton therapy treatment planning, both by
      comparing to other SPR methods proposed for single energy CT (SECT) and dual
      energy CT (DECT) as well as to experimental measurements. METHODS: A previously
      developed DECT-based SPR estimation method was adapted to PCD-CT data, by
      adjusting the estimation equations to allow for more energy spectra. The method
      was calibrated directly on noisy data to increase the robustness toward image
      noise. The new PCD SPR estimation method was tested in theoretical calculations
      as well as in an experimental setup, using both four and two energy bin PCD-CT
      images, and through comparison to two other SPR methods proposed for SECT and
      DECT. These two methods were also evaluated on PCD-CT images, full spectrum (one
      bin) or two-bin images, respectively. In a theoretical framework, we evaluated
      the effect of patient-specific tissue variations (density and elemental
      composition) and image noise on the SPR accuracy; the latter effect was assessed
      by applying three different noise levels (low, medium, and high noise). SPR
      estimates derived using real PCD-CT images were compared to experimentally
      measured SPRs in nine organic tissue samples, including fat, muscle, and bone
      tissues. RESULTS: For the theoretical calculations, the root-mean-square error
      (RMSE) of the SPR estimation was 0.1% for the new PCD method using both two and
      four energy bins, compared to 0.2% and 0.7% for the DECT- and SECT-based method,
      respectively. The PCD method was found to be very robust toward CT image noise,
      with a RMSE of 2.7% when high noise was added to the CT numbers. Introducing
      tissue variations, the RMSE only increased to 0.5%; even when adding high image
      noise to the changed tissues, the RMSE stayed within 3.1%. In the experimental
      measurements, the RMSE over the nine tissue samples was 0.8% when using two
      energy bins, and 1.0% for the four-bin images. CONCLUSIONS: In all tested cases,
      the new PCD method produced similar or better results than the SECT- and DECT
      based methods, showing an overall improvement of the SPR accuracy. This study
      thus demonstrated that PCD-CT scans will be a qualified candidate for SPR
      estimations.

PMID- 30191576
TI  - Circadian control of abscisic acid biosynthesis and signalling pathways revealed
      by genome-wide analysis of LHY binding targets.
AB  - The LATE ELONGATED HYPOCOTYL (LHY) transcription factor functions as part of the
      oscillatory mechanism of the Arabidopsis circadian clock. This paper reports the
      genome-wide analysis of its binding targets and reveals a role in the control of
      abscisic acid (ABA) biosynthesis and downstream responses. LHY directly repressed
      expression of 9-cis-epoxycarotenoid dioxygenase enzymes, which catalyse the rate
      limiting step of ABA biosynthesis. This suggested a mechanism for the circadian
      control of ABA accumulation in wild-type plants. Consistent with this hypothesis,
      ABA accumulated rhythmically in wild-type plants, peaking in the evening. LHY
      overexpressing plants had reduced levels of ABA under drought stress, whereas
      loss-of-function mutants exhibited an altered rhythm of ABA accumulation. LHY
      also bound the promoter of multiple components of ABA signalling pathways,
      suggesting that it may also act to regulate responses downstream of the hormone.
      LHY promoted expression of ABA-responsive genes responsible for increased
      tolerance to drought and osmotic stress but alleviated the inhibitory effect of
      ABA on seed germination and plant growth. This study reveals a complex
      interaction between the circadian clock and ABA pathways, which is likely to make
      an important contribution to plant performance under drought and osmotic stress
      conditions.

PMID- 30191577
TI  - Let go to grow: Reconciling your dependence on fluoroscopy for atrial
      fibrillation ablations.

PMID- 30191578
TI  - Nonparametric adaptive enrichment designs using categorical surrogate data.
AB  - Adaptive survival trials are particularly important for enrichment designs in
      oncology and other life-threatening diseases. Current statistical methodology for
      adaptive survival trials provide type I error rate control only under
      restrictions. For instance, if we use stage-wise P values based on increments of
      the log-rank test, then the information used for the interim decisions need to be
      restricted to the primary survival endpoint. However, it is often desirable to
      base interim decisions also on correlated short-term endpoints like tumor
      response. Alternative statistical approaches based on a patient-wise splitting of
      the data require unnatural restrictions on the follow-up times and do not permit
      to efficiently account for an early rejection of the primary null hypothesis. We
      therefore suggest new approaches that enable us to use discrete surrogate
      endpoints (like tumor response status) and also to incorporate interim rejection
      boundaries. The new approaches are based on weighted Kaplan-Meier estimates and
      thereby have additional advantages. They permit us to account for nonproportional
      hazards and are robust against informative censoring based on the surrogate
      endpoint. We will show that nonproportionality is an intrinsic and relevant issue
      in enrichment designs. Moreover, informative censoring based on the surrogate
      endpoint is likely because of withdrawals and treatment switches after
      insufficient treatment response. It is shown and illustrated how nonparametric
      tests based on weighted Kaplan-Meier estimates can be used in closed combination
      tests for adaptive enrichment designs, such that type I error rate control is
      achieved and justified asymptotically.

PMID- 30191579
TI  - Liver disease in cystic fibrosis: illuminating the black box.
AB  - Cystic fibrosis-associated liver disease (CFLD) has received increasing attention
      over the last three decades and has been recognized as a major comorbidity of CF,
      with potential impact on morbidity and survival of affected patients. This
      article is protected by copyright. All rights reserved.

PMID- 30191581
TI  - Pacemaker-mediated tachycardia: What is the mechanism?

PMID- 30191580
TI  - Worldwide pacemaker and defibrillator reuse: Systematic review and meta-analysis
      of contemporary trials.
AB  - BACKGROUND: Patients go without pacemaker, defibrillator, and cardiac
      resynchronization therapies (devices) each year due to the prohibitive costs of
      devices. OBJECTIVE: We sought to examine data available from studies regarding
      contemporary risks of reused devices in comparison with new devices. METHODS: We
      searched online indexing sites to identify recent studies. Peer-reviewed
      manuscripts reporting infection, malfunction, premature battery depletion, and
      device-related death with reused devices were included. The primary study outcome
      was the composite risk of infection, malfunction, premature battery depletion,
      and death. Secondary outcomes were the individual risks. RESULTS: Nine
      observational studies (published 2009-2017) were identified totaling 2,302
      devices (2,017 pacemakers, 285 defibrillators). Five controlled trials were
      included in meta-analysis (2,114 devices; 1,258 new vs 856 reused). All device
      reuse protocols employed interrogation to confirm longevity and functionality,
      disinfectant therapy, and, usually, additional biocidal agents, packaging, and
      ethylene oxide gas sterilization. Demographic characteristics, indications for
      pacing, and median follow-up were similar. There were no device-related deaths
      reported and no statistically significant difference in risk between new versus
      reused devices for the primary outcome (2.23% vs 3.86% respectively, P = 0.807,
      odds ratio = 0.76). There were no significant differences seen in the secondary
      outcomes for the individual risks of infection, malfunction, and premature
      battery depletion. CONCLUSIONS: Device reuse utilizing modern protocols did not
      significantly increase risk of infection, malfunction, premature battery
      depletion, or device-related death in observational studies. These data provide
      rationale for proceeding with a prospective multicenter noninferiority randomized
      control trial.

PMID- 30191582
TI  - Clinical experience with wearable cardioverter defibrillators at a tertiary
      electrophysiology program.
AB  - BACKGROUND: A wearable cardioverter defibrillator (WCD) is an alternative for
      patients who are not immediate candidates for an implantable cardioverter
      defibrillator (ICD). METHODS: Retrospective analysis of 242 patients prescribed a
      WCD from January 2014 through March 2015 with 1-year follow-up. RESULTS: A WCD
      was prescribed to 242 patients during the 15-month period. Forty-one patients
      were excluded due to lack of complete follow-up. The remaining 201 patients
      received a WCD for primary or secondary prevention of SCD. Seventy-nine percent
      of WCDs were prescribed by nonelectrophysiologists. Underlying etiologies for the
      WCD prescription included: 38% nonischemic cardiomyopathy, 25% recent myocardial
      infarction, 16% newly diagnosed ischemic cardiomyopathy, 12% documented
      ventricular arrhythmia, 6% ICD lead extraction, and 3% had high risk conditions
      for sudden cardiac death. During 1-year follow-up, 96 patients (48%) received an
      ICD and five patients (2.5%) received appropriate shocks and one patient (0.5 %)
      received an inappropriate shock. Other 105 (52%) patients subsequently did not
      require an ICD due to either improvement in ejection fraction, refusal of ICD
      therapy, or death. CONCLUSIONS: About half of patients prescribed a WCD
      subsequently receive an ICD and the rate of appropriate shock therapy from the
      WCD is 2.5%.

PMID- 30191583
TI  - Effect of pharmacological doses of niacin on testicular structure and function in
      normal and diabetic rats.
AB  - Male diabetic patients may experience adverse changes in testicular functions or
      structure. Niacin has antidyslipidemic properties in diabetic patients. We aimed
      to clarify the effect of pharmacological doses of niacin on testicular structure
      and function of normal and diabetic rats. Sixty adult male rats were treated as
      follows. Healthy control (HC); diabetic control (DC); NL and NH groups: normal
      rats that received niacin at 800 and 4,000 mg/kg of diet; DL and DH groups:
      diabetic rats that received niacin at 800 and 4,000 mg/kg diet for 50 days. In
      normal rats, obvious increase in serum testosterone especially in NL group
      associated with improved antioxidant status of testicular tissue was observed. In
      diabetic rats, niacin resulted in higher testicular weight/body weight and
      improved some histological parameters without affecting blood glucose,
      testosterone and sperm count. Testicular MDA content decreased. In conclusion,
      niacin especially at 800 mg/kg diet improves serum testosterone levels and
      antioxidant status of testes in normal rats. In diabetic rats, despite positive
      changes in histological features and antioxidant status of testes reproductive
      outcome including sperm count or testosterone levels were not improved. This
      study set the scene for further investigations on the effect of niacin on male
      reproductive system.

PMID- 30191584
TI  - Morphology of the vaginal complex in the white-eared opossum (Didelphis
      albiventris): Gross anatomy and light microscopy.
AB  - Opossums, the largest marsupials found in Brazil, are animals of great interest
      due to their commonality in large urban centres and their frequent use as
      laboratory animals. Thus, this study was designed to describe the vaginal complex
      in ten female opossums by gross anatomy and light microscopy. The vaginal complex
      comprises two lateral vaginae, a vaginal cul-de-sac and a urogenital sinus. No
      marked morphological contrast of the vaginal complex was observed in the
      proestrus and metestrus phases of the females studied. The epithelium lining of
      cul-de-sac was simple columnar and folded. The lateral vagina was lined by a
      stratified squamous epithelium that was keratinised in its cranial portion and
      nonkeratinised in the caudal region. The urogenital sinus was also lined by a
      stratified squamous epithelium. The morphology of vaginal complex of white-eared
      opossum is similar to those reported for other marsupials, showing similar
      histological features.

PMID- 30191586
TI  - The Implementation of Functional Family Therapy (FFT) as an Intervention for
      Youth Probationers in Singapore.
AB  - Family functioning is predictive of youth recidivism in Singapore. However, there
      is a lack of family based interventions for youth offenders on community
      probation. Evidence-based family interventions developed in Western populations,
      such as Functional Family Therapy (FFT), have been found to be effective in
      mitigating subsequent youth criminal behavior. However, no study has examined
      whether such interventions can be implemented and adapted for use in Eastern
      cultures. Thus, this paper sought to detail the implementation of FFT in
      Singapore. Rationale for the adoption of FFT is discussed, and key activities
      undertaken during the first 18 months of implementation are described.
      Preliminary data suggest that initial implementation efforts were successful.
      Challenges encountered, and implications in relation to the broader literature
      are discussed.

PMID- 30191587
TI  - A qualitative study of trainee experiences in Family Medicine-Obstetrics
      fellowships.
AB  - BACKGROUND: Family Medicine-Obstetrics fellowships provide family physicians with
      advanced obstetrics training. No accreditation system exists for these
      fellowships, which leads to variable training. Variation of fellows' experiences
      is not well understood. Our objective is to understand the motivations, training,
      and overall experiences of fellows in Family Medicine-Obstetrics fellowships,
      which may inform opportunities for improvement in fellowship design and suggest
      how Family Medicine-Obstetrics fellowship-trained physicians are prepared to
      practice among other obstetrics providers postgraduation. METHODS: We conducted
      semistructured interviews with current and past Family Medicine-Obstetrics
      fellows between Spring 2014 and Winter 2015. We used a snowball sampling
      approach. Interviews were recorded, transcribed, and coded following an inductive
      approach to content analysis. RESULTS: We contacted 47 and interviewed 21 current
      and past Family Medicine-Obstetrics fellows from 15 programs from across the
      country. Fellowships varied in cohort size, length, co-occurring presence of
      obstetrics and gynecology training programs, and structure and curriculum.
      Interviewees were motivated to complete a fellowship because of inadequate
      obstetrics training in residency, or because of an interest in rural or urban
      underserved practice. Fellowship experiences were shaped by fellowship
      leadership, program structure and curriculum, and relationships with
      obstetricians. Some felt prepared to forge collaborative professional
      relationships with obstetricians. CONCLUSIONS: The diversity of fellows'
      experiences suggests possible avenues of improvement for Family Medicine
      Obstetrics fellowships. These fellowships can prepare physicians to provide
      obstetric services in a variety of settings, including working in multispecialty
      integrated maternity care systems.

PMID- 30191588
TI  - Association between rs2278426 (C/T) and rs892066 (C/G) variants of ANGPTL8
      (betatrophin) and susceptibility to type2 diabetes mellitus.
AB  - BACKGROUND: Angiopoietin-like protein 8 (ANGPTL8) is a hormone that mainly
      secreted from the liver and adipose tissue and plays an important role in the
      proliferation of pancreatic beta cells and lipid metabolism. Therefore, we
      studied the association of ANGPTL8 rs2278426 (C/T) and rs892066 (C/G)
      polymorphisms with the risk of type 2 diabetes mellitus (T2DM) and their
      association with biochemical parameters. METHODS: Two hundred and eighty-eight
      subjects (controls; n = 138 and type 2 diabetic patients; n = 150) were enrolled
      in this study. Direct haplotyping was performed using amplification-refractory
      mutation system (ARMS)-RFLP-PCR. RESULTS: The CT genotype frequency of rs2278426
      (C/T) variant was significantly higher in T2DM patients compared to the controls
      group (P = 0.02), and there was a significant association between this genotype
      and increased risk of T2DM (OR: 2.41, CI: 1.26-4.59, P = 0.007). In addition,
      there was a significant relationship between CT genotype of this variant and high
      density lipoprotein cholesterol (HDL-C), fasting blood sugar (FBS), insulin,
      insulin resistance and glycated hemoglobin (P < 0.05). Furthermore,
      bioinformatics analysis revealed that arginine (Arg) to tryptophan (Trp)
      substitution at rs2278426 position causes structural instability of ANGPTL8
      protein. Genotype and allele distribution of rs892066 (C/G) was not statistically
      significant in T2DM patients compared to the control group. The distribution of
      haplotypes had no significant difference between controls and T2DM patients (P =
      0.24). CONCLUSION: Our results suggest that the rs2278426 (C/T) variant is
      associated with increased risk of T2DM and may cause dyslipidemia due to its
      effect on decreasing HDL-C levels.

PMID- 30191589
TI  - Pharmacophore modeling and molecular dynamics approach to identify putative DNA
      Gyrase B inhibitors for resistant tuberculosis.
AB  - One of the major mechanisms followed by the therapeutic agents to target the
      causative organism of TB, mycobacterium tuberculosis (Mtb), involves disruption
      of the replication cycle of the pathogen DNA. The process involves two steps that
      occur simultaneously, ie, breakage and reunion of DNA at gyrase A (GyrA) domain
      and ATP hydrolysis at gyrase B (GyrB) domain. Current therapy for multi-drug
      resistant TB involves FDA approved, Fluoroquinolone-based antibiotics, which act
      by targeting the replication process at GyrA domain. However, resistance against
      fluoroquinolones due to mutations in the GyrA domain has limited the use of this
      therapy and shifted the focus of the research community on the GyrB domain. Thus,
      this study involves in silico designing of chemotherapeutic agents for resistant
      TB by targeting GyrB domain. In the current study, a pharmacophore model for GyrB
      domain was generated using reported inhibitors. It was utilized as a query search
      against three commercial databases to identify GyrB domain inhibitors.
      Additionally, a qualitative Hip-Hop pharmacophore model for GyrA was also
      developed on the basis of some marketed fluoroquinolone-based GyrA inhibitors, to
      remove non-selective gyrase inhibitors obtained in virtual screening. Further,
      molecular dynamic simulations were carried out to determine the stability of the
      obtained molecules in complex with both the domains. Finally, Molecular mechanics
      with generalized Born and surface area solvation score was calculated to
      determine the binding affinity of obtained molecule with both domains to
      determine the selectivity of the obtained molecules that resulted in seven
      putative specific inhibitors of GyrB domain.

PMID- 30191590
TI  - Tributyltin oxide exposure impairs mouse oocyte maturation and its possible
      mechanisms.
AB  - Tributyltin oxide (TBTO) has been widely used as marine antifouling composition,
      preservative, biocide, and a stabilizer in plastic industry. Previous studies
      have indicated that TBTO can cause immunotoxicity as an environmental pollutant.
      However, little is known about its reproductive toxicity, especially on female
      oocyte maturation and the underlying mechanisms. In this study, mouse oocytes
      were cultured with different concentrations of TBTO in vitro, and several crucial
      events during meiotic maturation were evaluated. We found that the first polar
      body extrusion rate was significantly reduced, which reflected the disruption of
      meiotic maturation. The rate of abnormal spindle organization increased
      significantly, accompanied with a higher rate of chromosome misalignment. In
      addition, TBTO treatment increased reactive oxygen species generation markedly,
      which also accelerated the early-stage apoptosis. Moreover, heterogeneous
      mitochondrial distribution, mitochondrial dysfunction, and higher rate of
      aneuploidy were detected, which consequently disrupted in vitro fertilization. In
      conclusion, our results indicated that TBTO exposure could impair mouse oocyte
      maturation by affecting spindle organization, chromosome alignment, mitochondria
      functions, oxidative stress, and apoptosis.

PMID- 30191591
TI  - Evaluation of Ready, Set, BABY: A prenatal breastfeeding education and counseling
      approach.
AB  - BACKGROUND: Comprehensive prenatal education on infant feeding is recommended by
      many United States health organizations because of the need to maximize maternal
      preparedness for managing lactation physiology. Ready, Set, BABY (RSB) is a
      curriculum developed for counseling women about breastfeeding benefits and
      management including education on optimal maternity care practices. We
      hypothesized that RSB would be acceptable to mothers and that mothers' strength
      of breastfeeding intentions would increase, and their comfort with the idea of
      formula feeding would decrease after educational counseling using the materials.
      We also hypothesized that mothers' knowledge of optimal maternity care practices
      would increase after participation. METHODS: Materials were sent to a total of
      seven sites in the United States and Puerto Rico. Local health care practitioners
      completed training before counseling mothers with the curriculum. A pre- and
      postintervention questionnaire was administered to participants. Statistical
      analysis of results included paired t tests, Wilcoxon signed-rank tests, and
      McNemar's tests. RESULTS: Four hundred and sixteen expectant women participated.
      In the pre- and postintervention comparison, maternal participation in RSB
      significantly improved Infant Feeding Intentions Scale scores (P < 0.001) and
      knowledge of Baby-Friendly recommended maternity care practices (P < 0.001),
      while significantly decreasing comfort with the idea of formula feeding (P <
      0.001). The education materials were positively rated by participants.
      CONCLUSIONS: The findings indicate that the approach of using RSB in prenatal
      counseling group classes or individual sessions improves breastfeeding
      intentions. Future testing is needed to determine the effectiveness of the
      materials for impacting breastfeeding outcomes.

PMID- 30191592
TI  - Bone marrow-derived mesenchymal stem cells-derived exosomes prevent
      oligodendrocyte apoptosis through exosomal miR-134 by targeting caspase-8.
AB  - Ischemic stroke causes severe brain damage and remains one of the leading causes
      of morbidity and mortality worldwide. The microRNA-134 (miR-134) is involved in
      regulating the process of ischemia injury in neural cells and brain with ischemia
      stroke. The role of miR-134 in ischemic stroke remains poorly understood. The
      purpose of the current study was to investigate the effect of bone marrow-derived
      mesenchymal stem cells (BMSCs)-derived exosomal miR-134 on rat oligodendrocytes
      (OLs) apoptosis and its underlying mechanism of action. The results demonstrated
      that levels of miR-134 in BMSCs-exosome decreased but increased incaspase-8 after
      oxygen-glucose deprivation (OGD) treatment. Exosomal miR-134 significantly
      inhibited apoptosis by decreasing caspase-8 expression and activity in OGD
      treated group cultured with BMSCs-exosome and OLs. In addition, the miR-134
      mimics decreased caspase-8 expression in OGD-treated OLs, whereas miR-134
      inhibitors exacerbated the changes in the expression of the procaspase-8 and
      caspase-8 cleaved product proteins caused by OGD. The caspase-8 knockdown using
      caspase-8 small interfering RNA decreased OLs apoptosis, reversing the
      improvements that the miR-134 inhibited cells apoptosis by targeting caspase-8.
      Taken together, these results demonstrated that BMSCs-derived exosomes suppressed
      OLs apoptosis through exosomal miR-134 by negatively regulating the caspase-8
      dependent apoptosis pathway and may, therefore, be a novel potential therapeutic
      target for ischemic stroke treatment.

PMID- 30191593
TI  - Animal hoarding: The challenge for mental health, law enforcement, and animal
      welfare professionals.
AB  - Animal hoarding has been considered a significant problem by animal welfare and
      law enforcement professionals for over a century. However, it has only been
      recognized as an indication of a mental disorder in the last decade. I review the
      different forms that animal hoarding can take and the current understanding of
      the prevalence, demographics and possible etiology of this disorder. Conventional
      animal cruelty laws have often been inadequate to respond to animal hoarding
      cases until they reach levels that may involve serious harm to animals and
      people. I document how prosecution of such cases can be difficult and often does
      not adequately consider the mental health issues underlying the problem or the
      high likelihood of recidivism. Attempts to solve these problems by enacting new
      laws specifically addressing animal hoarding have been controversial and
      ineffective. I explore new approaches that coordinate a variety of community
      resources in response to hoarding cases that offer the best opportunity to
      respond to both the human and animal problems associated with animal hoarding.

PMID- 30191594
TI  - Performance comparison of blood collection tubes as liquid biopsy storage system
      for minimizing cfDNA contamination from genomic DNA.
AB  - BACKGROUND: The ratio of target cfDNA in total plasma is low. The abundant gDNA
      background resulting from blood cell lysis caused by improper operation has
      become a major obstacle to accurately measure cfDNA. In this study, we
      investigated the storage capacity of three blood cell collection tubes (BCTs) in
      the prevention of genomic DNA contamination caused by white blood cell rupture
      and evaluated their performance when they were utilized combining with highly
      sensitive mutation detection technology. METHODS: Blood samples were drawn from
      six healthy blood donors and stored in three types of BCTs (BD K2 -EDTA tube,
      Roche tube, and Streck tube). Plasma samples were isolated at specific time
      points (day 0, day 3, day 7, and day 14) for content analysis. RESULTS: Roche BCT
      was more capable for preventing cfDNA contamination caused by white blood cell
      disruption within 14 days, comparing with BD K2 -EDTA tube and Streck tube.
      Severe white blood cell lysis and gDNA contamination were found in the BD tube.
      The impacts of Roche and Streck tubes on the quantity and complexity of next
      generation sequencing (NGS) libraries did not differ significantly within 3 days,
      satisfying most of our daily demands. In addition, the rupture of WBC was not
      synchronized with hemolysis in BCTs. CONCLUSION: This study showed that
      capacities of blood collection tubes differed considerably in preservation of
      blood samples. Therefore, suitable blood collection devices should be selected to
      minimize gDNA contamination and to standardize blood samples processing for
      achieving more accurate and reliable clinical analysis of cfDNA.

PMID- 30191595
TI  - Free latissimus dorsi musculocutaneous flap for external hemipelvectomy
      reconstruction.
AB  - INTRODUCTION: External hemipelvectomy is one of the most extensive surgical
      procedures for locally advanced pelvic tumors. Stump coverage with the local
      tissues can be difficult in recurrent cases. Herein, we report our experience
      with immediate stump coverage using a free latissimus dorsi musculocutaneous
      (LDMC) flap after external hemipelvectomy for recurrent pelvic malignancies.
      METHODS: Six patients underwent external hemipelvectomy and immediate
      reconstruction using a free LDMC flap between November 2012 and June 2017. The
      mean age of the patients was 65 years (range: 63-69 years). The primary tumors
      were myxoid liposarcoma, chondrosarcoma, osteosarcoma, squamous cell carcinoma,
      and pleomorphic liposarcoma. A free LDMC flap was harvested from the ipsilateral
      back and transferred to the defect. When an intercostal nerve was found at the
      recipient site, the thoracodorsal nerve was coaptated with the intercostal nerve
      to reinnervate the muscle. RESULTS: The mean flap size was 23 * 10 cm and the
      range was 20 * 8-27 * 13.5 cm. The contralateral deep inferior epigastric vessels
      were used as recipient vessels in all patients. Thoracodorsal-intercostal nerve
      coaptation was performed in 2 patients. The flap survived in all patients. Three
      patients had complications of abscess formation. No patient developed
      postoperative hernia. CONCLUSION: Although it is challenging to do reconstruction
      after external hemipelvectomy, a free LDMC flap has several advantages, including
      a large coverage area, stability of circulation, ease of elevation, and
      preservation of the strength of the remaining abdominal wall. Technical tips for
      selecting anastomosis vessels are important and nerve coaptation could be
      effective.

PMID- 30191596
TI  - Molecular inhibitory mechanism study on the potent inhibitor brigatinib against
      four crizotinib-resistant ALK mutations.
AB  - As a potent and selective drug, brigatinib exhibits high efficacy against wild
      type and mutant anaplastic lymphoma kinase (ALK) proteins to treat non-small cell
      lung cancer. In this work, the mechanisms of brigatinib binding to wild type and
      four mutant ALKs were investigated to gain insight into the dynamic energetic and
      structural information with respect to the design of novel inhibitors. Comparison
      between ALK-brigatinib and ALK-crizotinib suggests that the scaffold of
      brigatinib is well anchored to the residue Met1199 of hinge region by two
      hydrogen bonds, and the residue Lys1150 has the strong electrostatic interaction
      with the dimethylphosphine oxide moiety in brigatinib. These ALK mutations have
      significant influences on the flexibility of P-loop region and DFG sequences, but
      do not impair the hydrogen bonds between brigatinib and the residue Met1199 of
      hinge region. And mutations (L1196M, G1269A, F1174L, and R1275Q) induce diverse
      conformational changes of brigatinib and the obvious energy variation of residues
      Glu1167, Arg1209, Asp1270, and Asp1203. Together, the detailed explanation of
      mechanisms of those mutations with brigatinib further provide several guidelines
      for the development of more effective ALK inhibitors.

PMID- 30191598
TI  - Corrigendum.

PMID- 30191597
TI  - Mesenchymal stem cell and bone marrow mononuclear cell therapy for
      cardiomyopathy: From bench to bedside.
AB  - To date, stem cell-based therapies for cardiac diseases have not achieved any
      significant clinical accomplishment. Globally, numerous patients are currently
      treated with autologous stem cells. The safety and practicality of this technique
      have been well-examined, its disadvantages have been recognized, and many trials
      have been proposed. Inadequate description of the implemented cell types, a
      variety of cell-handling proficiencies, and concerning factors related to
      autologous stem cells have been known as the central elements restricting the
      approval of cell-based therapies. The idea that bone marrow (BM)-derived cells
      could be applied to regenerate and cure damage in various organs is the basis for
      bone marrow mononuclear cell (BMMNC) therapy for heart disease. Mesenchymal stem
      cells (MSCs) are a part of the BMMNCs; on one hand, they have the capability to
      differentiate into various tissues, and, on the other, their immunomodulatory
      effects have been considered and clinically confirmed in different experiments.
      In this review, we summarize the knowledge obtained by trials in which
      mesenchymal cell-based therapy has been practiced. Furthermore, we accentuate the
      developments in the purification and lineage specification of MSCs as well as
      BMMNCs that have influenced the progress of future stem cell-based therapies with
      special attention on cardiovascular disease.

PMID- 30191599
TI  - Reply to the editor.

PMID- 30191600
TI  - A new system for classifying root and root canal morphology.

PMID- 30191601
TI  - Hairless regulates p53 target genes to exert tumor suppressive functions in
      glioblastoma.
AB  - Glioblastoma (GBM) is the most common malignant brain tumor and is associated
      with a poor prognosis, with most patients living less than a year after
      diagnosis. Given that GBM nearly always recurs after conventional treatments,
      there is an urgent need to identify novel molecular targets. Hairless (HR) is a
      nuclear factor enriched in the skin and has been previously implicated in hair
      cycling. HR is also highly expressed in the brain, but its significance is
      unknown. We found that human hairless gene (HR) expression is significantly
      decreased in all GBM subtypes compared with normal brain tissue and is predictive
      of prognosis, which suggests that loss of HR expression can contribute to GBM
      pathogenesis. HR was recently discovered to bind to and regulate p53 responsive
      elements, and thus we hypothesized that HR may have a tumor suppressive function
      in GBM by modulating p53 target gene expression. We found that HR indeed
      regulates p53 target genes, including those implicated in cell cycle progression
      and apoptosis in the GBM-derived U87 cell line, and restoring HR expression
      triggered G2/M arrest and apoptosis. An analysis of sequenced genomes from
      patients with GBM revealed 10 HR somatic mutations in patients with glioma, two
      of which are located in the histone demethylase domain of HR. These two
      mutations, P996S and K1004N, were reconstructed and found to have impaired p53
      transactivating properties. Collectively, the results of our study suggest that
      HR has tumor suppressive functions in GBM, which may be clinically relevant and a
      potential avenue for therapeutic intervention.

PMID- 30191602
TI  - Epigenetic silencing of sonic hedgehog elicits antitumor immune response and
      suppresses tumor growth by inhibiting the hedgehog signaling pathway in
      metastatic spine tumors in Sprague-Dawley rats.
AB  - BACKGROUND: Patients with metastatic spine tumors may suffer from pain or
      neurologic deficit, and the disease may be detected in patients with a known
      malignancy. Sonic hedgehog (SHH) has received special attention due to its role
      in cancers. Therefore, this study investigated the effects of epigenetic
      silencing of SHH on antitumor immune response and tumor growth by regulating the
      hedgehog (Hh) signaling pathway in metastatic spine tumors. METHODS: Rat models
      of metastatic spine tumors were successfully established. We first calculated the
      tumor volume and the inhibition rate of tumor growth to investigate the effect of
      SHH on tumor growth. Afterwards, immunohistochemistry was used to determine
      whether proliferation was delayed by SHH depletion, and the 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was conducted to test
      the changes in the lymphocyte transformation rate in the spleen triggered by SHH
      silencing. Then, the influence of SHH depletion on immune function was
      investigated. Later, quantitative reverse transcription polymerase chain reaction
      and Western blot assay were performed to explore the Hh signaling pathway-related
      factors. Finally, we added the Hh signaling pathway inhibitor, GDC-0449, to
      confirm the role of the pathway in tumor progression. RESULTS: Initially, we
      observed that SHH depletion was a negative factor for tumor growth. Afterwards,
      it was revealed that epigenetic silencing of SHH served as an inhibitor factor
      for the function of spleen lymphocyte transformation and inflammation while
      promoting antitumor immune function. CONCLUSION: Our preliminary results indicate
      that epigenetic silencing of SHH elicits an antitumor immune response and
      suppresses tumor growth by inhibiting the Hh signaling pathway in metastatic
      spine tumors.

PMID- 30191603
TI  - Novel mechanisms of regulation of the expression and transcriptional activity of
      hepatocyte nuclear factor 4alpha.
AB  - Hepatocyte nuclear factor 4alpha (HNF4alpha) is a master regulator of development
      and function of digestive tissues. The HNF4A gene uses two separate promoters P1
      and P2, with P1 products predominant in adult liver, whereas P2 products
      prevalent in fetal liver, pancreas, and liver/colon cancer. To date, the
      mechanisms for the regulation of HNF4A and the dynamic switch of P1-HNF4alpha and
      P2-HNF4alpha during ontogenesis and carcinogenesis are still obscure. Our study
      validated the previously reported self-stimulation of P1-HNF4alpha but
      invalidated the reported synergism between HNF4alpha and HNF1alpha. HNF4A-AS1, a
      long noncoding RNA, is localized between the P2 and P1 promoters of HNF4A. We
      identified critical roles of P1-HNF4alpha in regulating the expression of HNF4A
      AS1 and its mouse ortholog Hnf4a-os. Paired box 6 (PAX6), a master regulator of
      pancreas development overexpressed in colon cancer, cooperated with HNF1alpha to
      induce P2-HNF4alpha but antagonized HNF4alpha in HNF4A-AS1 expression. Thus, PAX6
      may be important in determining ontogenic and carcinogenic changes of P2
      HNF4alpha and HNF4A-AS1 in the pancreas and intestine. We also interrogated
      transactivation activities on multiple gene targets by multiple known and novel
      HNF4alpha mutants identified in patients with maturity onset diabetes of the
      young 1 (MODY1) and liver cancer. Particularly, HNF4alpha-D78A and HNF4alpha
      G79S, two mutants found in liver cancer with mutations in DNA-binding domain,
      displayed highly gene-specific transactivation activities. Interestingly,
      HNF4alpha-Q277X, a MODY1 truncation mutant, antagonized the transactivation
      activities of HNF1alpha and farnesoid X receptor, key regulators of insulin
      secretion. Taken together, our study provides novel mechanistic insights
      regarding the transcriptional regulation and transactivation activity of
      HNF4alpha in digestive tissues.

PMID- 30191604
TI  - Association of serum neuron-specific enolase and bilirubin levels with cerebral
      dysfunction and prognosis in large-artery atherosclerotic strokes.
AB  - PURPOSE: To explore the association of serum neuron-specific enolase (NSE) and
      bilirubin levels with cerebral dysfunction in the prognosis of large-artery
      atherosclerotic (LAA) stroke cases. METHODS: This study included 73 patients who
      suffered from LAA stroke and were divided into experimental group (n = 41) that
      had an increased serum NSE and bilirubin level, and control group (n = 32). At
      day 1, 7, and 14, the National Institutes of Health Stroke Scale (NIHSS) score,
      serum NSE, and bilirubin levels were measured. The modified Rankin Scale (mRS)
      was used to assess neurological functional recovery at 30 days. The good outcome
      rate was analyzed and tested using the Kaplan-Meier product-limit method and the
      log-rank test one year afterwards as a follow-up. RESULTS: The NIHSS scores,
      serum bilirubin, and NSE levels in the experimental group were significantly
      increased than that of control group at days 1, 7, and 14. There was a remarkable
      difference in the mRS scores and the good outcome rates between the two groups.
      Furthermore, the computed tomography detection rate of large-area cerebral
      infarctions was higher in the experimental group than that of control group.
      CONCLUSION: High serum NSE levels and hyperbilirubinemia might be biomarkers for
      a poor prognosis in the early identification of LAA strokes.

PMID- 30191605
TI  - Metabolic changes in adipose tissues in response to beta3 -adrenergic receptor
      activation in mice.
AB  - Brown and beige adipocytes dissipate energy as heat. Thus, the activation of
      brown adipocytes and the emergence of beige adipocytes in white adipose tissue
      (WAT) are suggested to be useful for preventing and treating obesity. Although
      beta3 -adrenergic receptor activation is known to stimulate lipolysis and
      activation of brown and beige adipocytes, fat depot-dependent changes in
      metabolite concentrations are not fully elucidated. The current study examined
      the effect of treatment with CL-316,243, a beta3 -adrenergic receptor agonist, on
      the relative abundance of metabolites in interscapular brown adipose tissue
      (iBAT), inguinal WAT (ingWAT), and epididymal WAT (epiWAT). Intraperitoneal
      injection of CL-316,243 (1 mg/kg) for 3 consecutive days increased the relative
      abundance of several glycolysis-related metabolites in all examined fat depots.
      The cellular concentrations of metabolites involved in the citric acid cycle and
      of free amino acids were also increased in epiWAT by CL-316,243. CL-316,243
      increased the expression levels of several enzymes and transporters related to
      glucose metabolism and amino acid catabolism in ingWAT and iBAT but not in
      epiWAT. CL-316,243 also induced the emergence of more beige adipocytes in ingWAT
      than in epiWAT. Furthermore, adipocytes surrounded by macrophages were detected
      in the epiWAT of mice given CL-316,243. The current study reveals the fat depot
      dependent modulation of cellular metabolites in CL-316,243-treated mice,
      presumably resulting from differential regulation of cell metabolism in different
      cell populations.

PMID- 30191606
TI  - Hepatobiliary and Pancreatic: Tumor to tumor metastasis from a primary insulinoma
      to a hepatic adenoma.

PMID- 30191607
TI  - Taxifolin prevents postprandial hyperglycemia by regulating the activity of alpha
      amylase: Evidence from an in vivo and in silico studies.
AB  - There has been a dramatic increase in the prevalence of diabetes mellitus (DM)
      and its associated complications globally. The postprandial stage of DM involves
      prompt elevation in the levels of blood glucose and alpha-amylase, a carbohydrate
      metabolizing enzyme is mainly involved in the regulation of postprandial
      hyperglycemia. This study was designed to assess the ability of a well-known
      flavonoid, taxifolin (TFN), against postprandial hyperglycemia and its inhibitory
      effects on alpha-amylase activity through the assessment of therapeutic
      potentials of TFN in an alloxan-induced diabetic animal model. The binding
      potential TFN with an alpha-amylase receptor was also investigated through
      molecular dynamics (MD) simulation and docking of to compare the binding
      affinities and energies of TFN and standard drug acarbose (ACB) with target
      enzyme. TFN significantly improved the postprandial hyperglycemia, lipid profile,
      and serum levels of alpha-amylase, lipase, and C-reactive protein in a dose
      dependent manner when compared with that of either DM-induced and ACB-treated
      alloxan-induced diabetic rats. Moreover, TFN also enhanced the anti-oxidant
      status and normal functioning of the liver in alloxan-induced diabetic rats more
      efficiently as compared to that of ACB-treated alloxan-induced diabetic rats.
      Therapeutic potentials of TFN were also verified by MD simulation and docking
      results, which exhibited that the binding energy and affinity of TFN to bind with
      receptor was significantly higher as compared to that of ACB. Hence, the results
      of this study signify that TFN might be a potent inhibitor of alpha-amylase that
      has the potential to regulate the postprandial hyperglycemia along with its anti
      inflammatory and anti-oxidant properties during the treatment of DM.

PMID- 30191608
TI  - miR-145 eliminates lipopolysaccharides-induced inflammatory injury in human
      fibroblast-like synoviocyte MH7A cells.
AB  - Recently, it has been accepted that miR-based therapy may be beneficial for
      rheumatoid arthritis (RA). This study aimed to evaluate the potential involvement
      of miR-145 in RA in vitro. The expression of miR-145 in the human fibroblast-like
      synoviocyte line MH7A was overexpressed by miR-mimic transfection, after which
      cells were subjected to lipopolysaccharides (LPS). Cell viability, apoptosis, and
      the release of pro-inflammatory cytokines were measured. The result showed that
      the apoptosis and the release of IL-1beta, IL-6, IL-8, and TNF-alpha were
      significantly induced by LPS. Meanwhile, LPS treatment led to downregulation of
      miR-145. miR-145 overexpression in LPS-untreated MH7A cells had no impacts on
      cell apoptosis and inflammation. But, restoring miR-145 expression in LPS
      stimulated cells by supplementation of a miR-145 mimic protected MH7A cells
      against LPS-induced apoptosis and inflammation. Furthermore, miR-145
      overexpression in LPS-untreated MH7A cells slightly blocked the PI3K/ATK and mTOR
      pathways, whereas miR-145 overexpression in LPS-stimulated cells notably
      repressed the LPS-induced activation of PI3K/ATK and MAPK/mTOR pathways. Our
      study suggested that miR-145 protected MH7A cells against LPS-induced apoptosis
      and inflammation by inhibiting the PI3K/AKT and MAPK/mTOR pathways.

PMID- 30191609
TI  - Structural insights of resveratrol with its binding partners in the toll-like
      receptor 4 pathway.
AB  - The benefits associated with resveratrol (Resv; 3,4',5-trihydroxy-trans-stilbene)
      are known for a long time. The therapeutic properties of Resv are observed in
      diseases like cancer, neurological disorders, atherosclerosis, aging,
      inflammation, etc. Multiple studies suggest that the beneficial properties of
      Resv are due to its binding to targets in multiple pathways. The same has been
      reflected in inflammation, where Resv has been shown to inhibit nuclear factor
      kappa light-chain enhancer of activated B cells in the toll-like receptor 4
      (TLR4) pathway. There are multiple cellular targets which bind to Resv, however
      the mode and the key interactions involved remain elusive for many of them. In
      the current work, we have investigated the structural insights of Resv with three
      of its binding partners involved in the inflammatory TLR4 signaling pathway.
      Through a structure-based modelling and molecular dynamics study, we have
      unraveled the molecular and atomic interactions involved in the Resv-binary
      complexes of inhibitor of kappaB kinase, cyclooxygeanse-2, and tank-binding
      kinase I, all three of which are key players in TLR4 inflammatory signaling. This
      study is the latest addition to the investigations of the structural partners of
      Resv and its molecular interactions.

PMID- 30191610
TI  - Lipophilic statins antagonistically alter the major epithelial-to-mesenchymal
      transition signaling pathways in breast cancer stem-like cells via inhibition of
      the mevalonate pathway.
AB  - Resistance to therapies, recurrence, and metastasis remain challenging issues for
      breast cancer patients, particularly for triple-negative and breast cancer stem
      cells. The activation of the epithelial-to-mesenchymal transition (EMT) plays an
      indispensable role in the poor prognosis of those types. The accumulating proofs
      indicated that the mevalonate pathway crucially mediates a poor prognosis. Here,
      the effects of lipophilic 3-hydroxy-3-methyl-glutaryl-coenzyme A inhibitors,
      atorvastatin, lovastatin, and simvastatin, were investigated on expression and
      function of a selected profile of EMT-related genes in breast cancer stem-like
      cells. A nontoxic dose of statins (5 MUM for 4 days) significantly (P < 0.05 and
      >2-fold change) altered expression of 50 of 71 studied genes with a shared
      cluster of 37 genes that are coding chief operator of signaling pathways in
      Hippo, Notch, Wnt, proliferation, invasion, angiogenesis, and cell death. They
      also significantly decreased the levels of Yap/Taz proteins and shifted the
      expression of vimentin/E-cadherin in favor of induction of differentiation.
      Statins significantly chemosensitized the treated cells to doxorubicin and also
      reduced in vitro migration of the cells. Whereas lovastatin and simvastatin
      significantly decreased the expression of CD44, atorvastatin drastically
      increased CD24 and caused more wide-ranging impacts. In summary, the statins hold
      back the process of EMT by the antagonizing of EMT-promoting pathways. High
      degree of overlapping findings is supportive of the central role of the
      mevalonate pathway in cancer stem-like cells, but further studies are required to
      find the optimized chemical structure for the maximum abrogation of orchestrated
      EMT pathways.

PMID- 30191611
TI  - Early-life exposure to gut microbiota from disease-protected mice does not impact
      disease outcome in type 1 diabetes susceptible NOD mice.
AB  - The microbial community making up the gut microbiota can profoundly influence
      intestinal homeostasis and immune system development, and is believed to
      influence the development of complex diseases including type 1 diabetes (T1D).
      T1D susceptible nonobese diabetic (NOD) mice have been shown to harbor a distinct
      microbiota to disease-protected mice. We hypothesized that the T1D susceptible
      genetic background of NOD mice would be resistant to the introduction of a
      C57BL/6-derived microbiota. NOD and C57BL/6 mice were cohoused either continually
      from birth, from birth until weaning or from weaning onwards, allowing transfer
      of microbiota between the mice. Cohousing NOD with C57BL/6 mice from before
      birth, resulted in moderate changes to the gut microbiota, whereas initiating
      cohousing at weaning only led to minimal changes. Terminating cohousing at
      weaning reduced the changes in the microbiota composition. However, diabetes
      onset was not significantly delayed and there was no reduction in intestinal
      inflammation or the proportion of regulatory T cells in the cohoused NOD mice.
      However, insulin but not islet-specific glucose-6-phosphatase catalytic subunit
      related protein-specific CD8+ T cells were reduced by cohousing suggesting an
      epitope-specific modulation of the autoreactive response by the gut microbiota.
      These results suggest that the T1D susceptible genetic background of the NOD
      mouse was resistant to the introduction of a C57BL/6-derived microbiota.

PMID- 30191612
TI  - A rare case of intravascular schwannoma.

PMID- 30191613
TI  - Exploration and validation of diphosphate-based Plasmodium LytB inhibitors using
      computational approaches.
AB  - LytB or IspH is an indispensable enzyme and a suitable drug target of Plasmodium
      falciparum that participate in isoprenoid biosynthesis of nonmevalonate pathway
      (MEP). Recently, we have investigated the structural dynamics of Plasmodium LytB
      and proposed some novel diphosphate-based inhibitors using molecular modeling and
      docking studies. Here, we have tried to characterize those previously screened
      molecules by quantitative structure activity relationships and pharmacophore
      based analyses, as well as validated the dynamics of their interactions with LytB
      protein. Five total compounds having PubChem CID 516, 125696, 165275, 448012, and
      9921431 were predicted with significant inhibitory activity by quantitative
      structure activity relationships and pharmacophore models. Again, the molecular
      dynamics simulation results showed that these five compounds are able to form
      stable complexes with the receptor through many direct and water mediated
      interactions. The binding free energies calculated by Poisson-Boltzmann surface
      area method resulted within the range between -99.77 and - 43.74 kcal/mol, which
      favoured their profound inhibitory affinity. Residues of LytB like His41, His74,
      Ser222, Ser223, and Asn224 in LytB were the main protagonists in contributing the
      majority of interaction energies to the ligands. Finally, the ADMET, toxicity,
      and drug-likeness scores also affirm these compounds to be considered for further
      development of new antimalarial inhibitor in the future.

PMID- 30191614
TI  - Prevalence and zoonotic risk of tropical rat mite (Ornithonyssus bacoti) in
      exotic companion mammals in southern Italy.
AB  - BACKGROUND: Exotic companion mammals are popular pets worldwide. They are a
      potential source of zoonotic infections transmissible to their owners.
      HYPOTHESIS/OBJECTIVES: To determine the prevalence and zoonotic risks of tropical
      rat mite (Ornithonyssus bacoti) in exotic companion mammals in Italy. ANIMALS:
      The records of 782 exotic pet mammals seen in multiple veterinary clinics (n =
      20), pet shops (n = 10) and private breeders (n = 2) around Naples (Italy) were
      searched. METHODS AND RESULTS: The isolation of O. bacoti was the only inclusion
      criterion. Relative (in the subgroups) and absolute prevalence (in the entire
      population sampled) of clinical signs in pets and owners were calculated. The
      prevalence of clinical signs in pets and their owners was also calculated based
      on their housing (pet shops versus private housing) using Fisher's exact test. A
      P-value < 0.05 was considered significant. Seventy seven records (9.8%) of
      animals infested were identified. Of those, 33.8% (26 of 77) were hamsters, 25.9%
      (20 of 77) gerbils, 11.7% (nine of 77) guinea pigs, 7.8% (six of 77) rabbits,
      7.8% (six of 77) degus, 5.2% (four of 77) kangaroo mice, 2.6% (two of 77)
      hedgehogs, 2.6% (two of 77) squirrels and 2.6% (two of 77) were sugar gliders.
      The frequency of owners affected by the rat mite dermatitis was very high in
      gerbils (20 of 20), hamsters (21 of 26) and guinea pigs (seven of nine).
      CONCLUSIONS AND CLINICAL IMPORTANCE: The results of the present survey indicate
      that exotic pet mammals may serve as an active reservoir for O. bacoti
      infestation. The results of this study also suggest a lack of species specificity
      for O. bacoti when favourable conditions are present (overcrowding).

PMID- 30191615
TI  - The use of fluorescent staining techniques for microscopic investigation of
      polymorphonuclear leukocytes and bacteria.
AB  - The use of fluorescent stains to visually investigate eukaryotic and/or
      prokaryotic cells is increasing quickly and manuscripts within all areas of
      research publish results using fluorescent staining techniques. However, in
      contrast to literature on traditional histological staining techniques, the
      literature on fluorescent stains and staining techniques does not offer as good
      an illustration of cellular morphology. The aim of this guideline is to
      illustrate different fluorescent stains and staining techniques for imaging
      immune cells, in particular the polymorphonuclear leukocytes (PMNs), in
      combination with infecting bacteria as seen in chronic bacterial infections.
      Thereby providing the first guideline for the morphology and identification of
      fluorescently stained PMNs, bacteria and biofilm.

PMID- 30191616
TI  - Potential clinical implications of HPV status and expressions of p53 and cyclin
      D1 among oropharyngeal cancer patients.
AB  - BACKGROUND: There is increasing evidence that high-risk human papillomavirus
      plays significant role in oropharyngeal cancer; however, there is lack of
      knowledge on the interplay between the virus and its downstream-related molecules
      and their possible prognostic values. The objectives of the study are to better
      understand the interplay of the HR-HPV and its associated downstream molecules
      and to evaluate potential biomarkers for patient outcomes. METHODS: We conducted
      a retrospective study with available formalin-fixed, paraffin-embedded tissue
      from 244 oropharyngeal cancer patients that received curative radiotherapy or
      concurrent chemoradiotherapy from 2000 to 2008. In addition to chart review, we
      performed HPV DNA and RNA in situ hybridization and immunohistochemistry for p53,
      the retinoblastoma protein, p16, and cyclin D1 analysis. Cox proportional hazard
      and Kaplan-Meier survival analysis were used to determine the prognostic markers
      for clinical outcomes. RESULTS: Patients averaged 57.3 +/- 9.4 year-old and were
      mostly males (76.2%) and ever-smokers (76.2%). All patients received curative
      radiotherapy, and 44.3% received concurrent chemoradiotherapy. We detected the
      human papillomavirus in 77.9% of study patients. Ever-smokers, more advanced
      tumor stage, and receiving radiotherapy only had poorer 5-year overall survival,
      disease-specific survival, and loco-regional recurrence. Cases with positive
      human papillomavirus and p53 overexpression had poorer disease-specific survival.
      Cases without human papillomavirus, but cyclin D1 overexpression, were associated
      with poorer 5-year overall survival. CONCLUSIONS: Our data suggest that
      additional p53 and cyclin D1 testing may benefit oropharyngeal cancer patients
      with known human papillomavirus status.

PMID- 30191617
TI  - C3-C3' and C6-C6' Oxidative Couplings of Carbazoles.
AB  - 9-Substituted carbazoles are widely used units in materials science, and their
      oxidative reactions have been utilized for the synthesis and characterization of
      polymers. Though the oxidative mechanism of carbazoles has been known for a few
      decades, structural definition has remained difficult, because their polymers are
      generally insoluble with incomplete characterization and unknown dependence of
      the electrochemical potentials. The oxidative reactions of 9-substituted
      carbazoles should be carefully considered under specific oxidative conditions;
      otherwise, structure definitions could be wrong, because the IR and NMR spectra
      used previously cannot quantitatively analyze 3,3'-coupling and 6,6'-coupling of
      carbazoles. In this review, the best understanding of the C3-C3' and C6-C6'
      oxidative couplings of 9-substituted carbazoles is presented, and the benefit of
      these oxidative reactions from the viewpoints of electrochemical synthesis, film
      engineering, and the synthesis and processing of polymers is highlighted.

PMID- 30191618
TI  - Performance characteristics of newer MIC gradient strip tests compared with the
      Etest for antimicrobial susceptibility testing of Neisseria gonorrhoeae.
AB  - For Neisseria gonorrhoeae susceptibility testing, Etest, comparable to agar
      dilution, is frequently used. In recent years, newer MIC gradient strip tests
      have been commercialized. However, these tests have not been appropriately
      evaluated for gonococci. We evaluated the sensitivity, specificity, accuracy,
      quality, availability of antimicrobials and cost of the MIC Test Strip
      (Liofilchem), M.I.C.Evaluator (Oxoid) and Ezy MIC Strip (HiMedia), compared to
      the reference Etest (bioMerieux), for gonococcal susceptibility testing. The MICs
      of eight antimicrobials in 103 gonococcal international reference strains (n =
      29) and clinical isolates (n = 74) were examined. Coefficient of determination
      (R2 ), complete agreement, essential agreement, SIR categorical agreement,
      sensitivity, specificity and accuracy were calculated. R2 of the MICs for the
      antimicrobials ranged between 0.674-0.996, 0.617-0.993, and 0.643-0.994 for the
      MIC Test Strip, M.I.C.Evaluator strips and Ezy MIC Strips respectively. The
      essential agreement (SIR categorical agreement) was 99.6% (88.6%), 100% (87.1%)
      and 93.0% (83.1%) respectively. M.I.C.Evaluator strips for gonococcal key
      antimicrobials were lacking and the Ezy MIC Strips showed an inconsistent
      accuracy, quality and some strips were contaminated. The Liofilchem MIC Test
      Strips had limitations, but might be relatively accurate alternatives to Etest
      for gonococci. Strict quality assurance (at manufacturing and testing
      laboratory), including quality controls, are required.

PMID- 30191619
TI  - Performance of Semiconductor sequencing platform for non-invasive prenatal
      genetic screening for fetal aneuploidies: results from a multicenter prospective
      cohort study in a clinical setting.
AB  - OBJECTIVES: To validate and evaluate an integrated protocol for non-invasive
      prenatal genetic screening (NIPS) for common fetal aneuploidies in a clinical
      setting, using the semiconductor sequencing technology, Ion Proton. METHODS: This
      prospective cohort study included 2505 pregnant women from seven academic genetic
      laboratories (695 high risk pregnancies in a validation study and 1810
      pregnancies with a risk higher than 1/250 without ultrasound anomalies, in a real
      NIPS clinical setting). Cell free DNA from plasma samples was sequenced using Ion
      Proton sequencer, and sequencing data were analyzed using the open-access
      software WISECONDOR. Performance metrics for detection of trisomies 21, 18 and
      13, were calculated based on either fetal karyotype result or clinical data
      collected at birth. We also evaluated the failure rate and compared three methods
      of fetal fraction quantification (RASSF1A assay, DEFRAG and SANEFALCON software).
      RESULTS: Sensitivities and specificities were: 98.3% (95%CI: 93.5 - 99.7) and
      99.9% (95%CI: 99.4 - 100) for T21, 96.7% (95%CI: 80.9 - 99.8) and 100% (95%CI:
      99.6 - 100) for T18, 94.1% (95%CI: 69.2 - 99.7) and 100% (95%CI: 99.6 - 100) for
      T13. Our failure rate was 1.2% at first and as low as 0.6% after re-testing some
      of the failed samples. Fetal fraction estimation by RASSF1A assay was consistent
      with DEFRAG results, both of which are adequate for routine diagnosis.
      CONCLUSIONS: We describe one of the largest studies evaluating the Ion Proton
      based NIPS and the first clinical study reporting pregnancy outcome in a large
      set of patients. We demonstrate that this platform is highly efficient in
      detecting the three most common trisomies. Our protocol is robust and can be
      easily implemented in any medical genetics laboratory. This article is protected
      by copyright. All rights reserved.

PMID- 30191620
TI  - Mechanistic Variants in Methane Activation Mediated by Gold(I) Supported on
      Silicon Oxide Clusters.
AB  - Cationic gold has been frequently identified as a suitable reactive species for
      activating methane in condensed-phase studies. However, it is far from clear how
      the coordination site manipulates the activity of such species. Herein, by
      anchoring AuI on silicon oxide cluster supports of variable sizes, the site
      specific methane activation by AuI -Ox has been clarified by mass spectrometry in
      conjunction with quantum chemistry calculations. An unexpected mechanistic switch
      in C-H activation was identified for the cluster anions Au(SiO2 )n O- (n=1-3)
      that selectively activate one of the four C-H bonds of methane with different
      reaction efficiencies: a low efficiency was observed for the two-fold-coordinated
      gold ion (AuI, 2f ), which was anchored on an AuSiO3 - or AuSi2 O5 - cluster,
      through an oxidative addition mechanism (a homolytic process), and high
      efficiency was observed for the one-fold-coordinated gold ion (AuI, 1f ), which
      was supported on an AuSi3 O7 - cluster, through Lewis acid/base pairs mechanism
      (AuI, 1f ???O2- , a heterolytic process). Fine regulation of the 5d orbital level
      of the Au atom by the oxygen ligands accounted for the mechanistic difference
      between AuI, 2f and AuI, 1f species. The mechanistic understanding of the
      reactivity of AuI -Ox at a strictly molecular level can be used to clarify the
      dissimilar activity of gold anchored on different oxide supports.

PMID- 30191622
TI  - The efficacy of coronary sinus reducer in patients with refractory angina-A
      systematic review of the literature.
AB  - OBJECTIVES: The aim of our systematic review was to investigate the efficacy of
      coronary sinus (CS) reducer device in patients with refractory angina.
      BACKGROUND: The CS reducer device provides a therapeutic option for patients with
      coronary artery disease who are not suitable for revascularization. METHODS: Two
      independent investigators (GB and GT) systematically searched the Medline and
      Cochrane library databases for studies describing the efficacy and safety of the
      CS reducer in patients with refractory angina from January 1, 2000 until May 12,
      2018 using the following terms: "coronary sinus (reducer OR reducing) device."
      Efficacy was defined as >=1 unit improvement in the Canadian cardiovascular
      society (CCS) score. RESULTS: Our search strategy provided six studies (five
      observational studies and one randomized clinical trial) with 196 patients. The
      CS reducer device was effective in 146/186 (78.5%) patients. CCS score improved
      from 3.2 at baseline to 1.9 after 8.6 months of follow-up. The efficacy of CS
      reducer device was also demonstrated as an improvement in Seattle Angina
      Questionnaire score, dobutamine echocardiography, thalium single-photon emission
      computed tomography perfusion studies, 6-min-walk test and myocardial perfusion
      reserve index. Implantation failed in 4 of 196 (2%) patients and 5 patients
      (2.5%) had a complication during 30-day follow-up. CONCLUSIONS: The CS reducer is
      a promising treatment option for patients with refractory angina who are not
      candidates for revascularization. However, larger randomized control trials with
      long-term follow-up are needed to elucidate its role.

PMID- 30191621
TI  - Predictive value of combined analysis of pro-NPY and ERG in localized prostate
      cancer.
AB  - This study aimed to investigate if combined analysis of pro-Neuropeptide Y (NPY)
      and ERG expression in tumor tissue are associated with biochemical failure (BF),
      castration-based treatment, castration-resistant prostate cancer (CRPC), and
      prostate cancer (PCa)-specific death for men undergoing radical prostatectomy
      (RP) for PCa. This study included 315 patients, who underwent RP from 2002 to
      2005. Both pro-NPY and ERG expression were analyzed using immunohistochemistry
      and were scored as low or high and negative or positive, respectively. Risk of
      BF, castration-based treatment, CRPC, and PCa-specific death were analyzed with
      multiple cause-specific Cox regression analyses and stratified cumulative
      incidences using competing risk assessment. Median follow-up was 13.0 years (95%
      CI: 12.7-13.2). In total, 85.7% were pro-NPY high and 14.3% were pro-NPY low. The
      combined analyses of pro-NPY and ERG expression was not associated with risk of
      BF (p = 0.7), castration-based treatment (p = 0.8), CRPC (p = 0.4) or PCa
      specific death (p = 0.5). In the multiple cause-specific Cox regression analysis,
      pro-NPY high and ERG positivity was not associated with BF (HR: 1.02; 95% CI 0.6
      1.7; p = 0.94). In conclusion the combination of pro-NPY and ERG expression did
      not show association with risk of BF, castration-based treatment, CRPC, and PCa
      specific death following RP.

PMID- 30191623
TI  - Daidzein, its effects on impaired glucose and lipid metabolism and vascular
      inflammation associated with type 2 diabetes.
AB  - Over the last decades, the incidence of type 2 diabetes (T2D) is increasing
      substantially. Emerging evidences from epidemiological studies have shown the
      association between higher intake of soy isoflavones and reduced risk of T2D and
      its associated health risks. Daidzein, a soy isoflavone, has been found to have a
      promising therapeutic potential in managing T2D pathophysiology. Fermented
      soybean is the major source of daidzein; however, it can also be formed via the
      consumption of its glycosylated moiety, daidzin with subsequent hydrolysis by
      intestinal bacterial enzyme. Many studies reported the prophylactic effect of
      daidzein on the improvement of hyperglycemia, insulin resistance, dislipidemia,
      obesity, inflammation, and other complications associated with T2D. The molecular
      mechanisms underlying the action of daidzein include diverged pathways where
      daidzein has been shown to interact with several signaling molecules and
      receptors to achieve desirable effect. Although the specific molecular mechanism
      is still elusive, further studies are thus needed to understand it in detail. In
      this review, we discuss the antidiabetic potential of daidzein with respect to
      the evidences from various clinical, preclinical, and cell culture studies and
      the underlying molecular mechanism in a precise way to have a comprehensive
      account on this isoflavone with promising therapeutic potential. (c) 2018
      BioFactors, 44(5):407-417, 2018.

PMID- 30191624
TI  - Comprehensive characterisation of polyphenols in leaves and stems of three anti
      dengue virus type-2 active Brazilian Faramea species (Rubiaceae) by HPLC-DAD-ESI
      MS/MS.
AB  - INTRODUCTION: The methanol (MeOH) leaf extracts of the species Faramea bahiensis,
      F. hyacinthina and F. truncata (Rubiaceae) have previously shown in vitro non
      cytotoxic and anti-dengue virus serotype 2 (DENV2) activities in human
      hepatocarcinoma cell lineage (HepG2). Chemical studies have led to the isolation
      of major flavonoids, but quite complex fractions of phenolic compounds still
      remain. OBJECTIVE: To complete the study of phenolic compounds in the leaves and
      to access the presence of these compounds in the stems of these Faramea spp. by
      online high-performance liquid chromatography-diode array detector-electrospray
      ionisation tandem mass spectrometry (HPLC-DAD-ESI-MS/MS), as well as to evaluate
      the in vitro cytotoxic and anti-DENV2 activities of their MeOH stem extracts.
      METHODOLOGY: The identification was performed by comparing retention times, UV
      and mass spectra with those of available standards and by using the mechanisms
      and fragmentation patterns established in previous studies. The effects of the
      extracts in DENV2 infected HepG2 cell viability was determined by 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The virus
      titer was quantified by plaque assay. RESULTS: The study led to the
      characterisation of 31 phenolic compounds including flavonoid O- and C
      glycosides, phenolic acids and one coumarin. The stem extracts from F.
      hyacinthina and F. bahiensis presented a similar bioactivity to those of their
      leaves but a loss of cytoprotective activity of F. bahiensis and a higher
      cytotoxicity of F. truncata were observed. CONCLUSIONS: This research allowed a
      detailed phenolic composition of three bioactive Faramea species to be achieved,
      thus contributing to the study of this genus and providing valuable information
      for further phytotherapeutic applications.

PMID- 30191625
TI  - Quadratic and Cubic Optical Nonlinearities of Y-Shaped and Distorted-H-Shaped
      Arylalkynylruthenium Complexes.
AB  - Straightforward syntheses of bis[bis{1,2-bis(diphenylphosphino)ethane}ruthenium]
      functionalized 1,3,5-triethynylbenzene-cored complexes via a methodology
      employing "steric control" permit facile formation of Y-shaped Sonogashira
      coupling products and distorted-H-shaped homo-coupled quadrupolar products.
      Cyclic voltammetric data from these products reveal two reversible metal alkynyl
      localized oxidation processes for all complexes. The wavelengths of the linear
      optical absorption maxima are dominated by the nature of the peripheral alkynyl
      ligand rather than the substituent at the unique arm of the "Y" or at the
      quadrupolar complex "core". The quadratic optical nonlinearities of the Y-shaped
      complexes were assessed by the hyper-Rayleigh scattering technique at 800 nm and
      employing 100 fs light pulses; introduction of donor NEt2 and/or acceptor NO2 to
      the wedge periphery resulted in non-zero nonlinearities, with the largest
      betaHRS,800 values being observed for the complexes containing the 4
      nitrophenylalkynyl ligands. Depolarization ratios are consistent with substantial
      off-diagonal first hyperpolarizability tensor components and 2D nonlinear
      character. Computational studies employing time-dependent density functional
      theory have been employed to assign the key low-energy transitions in the linear
      optical spectra and to compute the quadratic nonlinear optical tensorial
      components. Cubic optical nonlinearities of the quadrupolar complexes were
      assessed by the Z-scan technique over the range 500-1600 nm and employing 130 fs
      light pulses; two-photon absorption cross-sections for these distorted-H-shaped
      complexes are moderate to large in value (up to 5500 GM at 880 nm), while one
      example displays significant three-photon absorption (1300*10-80  cm6  s2 at 1200
      nm).

PMID- 30191626
TI  - Effects of calpain inhibitor on the apoptosis of hepatic stellate cells induced
      by calcium ionophore A23187.
AB  - We previously showed that changes in calcium concentrations were related to cell
      apoptosis in vitro. The endoplasmic reticulum (ER) is the main component of
      calcium storage and signal transduction, and disrupting the balance of
      intracellular Ca2+ can cause endoplasmic reticulum stress (ERS). In this process,
      the ER releases stored Ca 2+ into the cytoplasm and activates calpain-2. To
      further investigate the effect of calpain in hepatic stellate cells (HSCs), in
      the current study, we examine the effect of N-acetyl-leu-leu-norleucinal (ALLN)
      on apoptosis resulting from calcium ionophore A23187-induced ERS. Our findings
      indicate that calpain inhibition reduces calcium ionophore A23187-induced
      apoptosis of HSCs and decreases the expression of ER stress proteins that may be
      related to the calpain/caspase signaling pathway.

PMID- 30191628
TI  - Surgical approaches in women with endometrial cancer with a body mass index
      greater than 35 kg/m2.
AB  - AIM: Endometrial cancer is often associated with obesity. We want to compare the
      outcomes of surgical staging according to the surgical approach in patients with
      a body mass index >=35 kg/m2 . METHODS: A retrospective cohort study with 138
      patients with endometrial cancer and body mass index >=35 kg/m2 with different
      surgical staging routes: laparotomy (LPT; n = 94) and minimally invasive surgery
      (MIS): laparoscopy (LPC; n = 18) + robotic assisted laparoscopy (n = 26).
      RESULTS: Lymphadenectomy rate was similar in the three groups; there were no
      differences in the number of nodes removed. Decreased bleeding (P = 0.002) and
      hospital admission length (P < 0.001) was observed in the endoscopic group. Less
      early-postoperative complications were observed in the robotic approach (P =
      0.007). Significant differences were not observed in recurrence-free survival or
      in overall survival. CONCLUSION: Minimal invasive surgical staging in obese women
      with endometrial cancer could represent the surgical route of choice because it
      decreases operative bleeding, hospital admission length and the early
      postoperative complication rate without compromising recurrence-free survival or
      overall survival.

PMID- 30191627
TI  - Postnatal deficiency of ADAMTS1 ameliorates thoracic aortic aneurysm and
      dissection in mice.
AB  - NEW FINDINGS: What is the central question of this study? Thoracic aortic
      aneurysm and dissection (TAAD) is characterized by extracellular matrix
      remodelling and an inflammatory response. Evidence suggests that ADAMTS1 is
      closely associated with TAAD development, but whether it contributes to the
      pathophysiology of TAAD remains unknown. What is the main finding and its
      importance? We generated inducible postnatal ADAMTS1 knockout mice and found that
      ADAMTS1 deficiency attenuated beta-aminopropionitrile-dependent TAAD formation
      and rupture. Furthermore, ADAMTS1 deficiency suppressed neutrophil and macrophage
      infiltration by inhibiting inflammatory cytokine levels and macrophage migration
      during the early stage of beta-aminopropionitrile-induced TAAD. ADAMTS1 could be
      a new therapeutic target for TAAD. ABSTRACT: Thoracic aortic aneurysm and
      dissection (TAAD), as a life-threatening cardiovascular disease, is characterized
      by extracellular matrix remodelling and an inflammatory response. A disintegrin
      and metalloproteinase with thrombospondin motifs 1 (ADAMTS1) is an inflammation
      related protein that is able to degrade extracellular matrix proteins in
      arteries. Herein, we investigated whether ADAMTS1 contributes to the
      pathophysiology of TAAD in mice. Using the mouse model of beta-aminopropionitrile
      (BAPN)-induced TAAD, we found that ADAMTS1 expression was upregulated beginning
      in the early stage of TAAD development and localized predominantly in the aortic
      adventitia. ADAMTS1-floxed mice and whole-body tamoxifen-inducible ADAMTS1
      knockout mice (ADAMTS1flox/flox Ubc-CreERT2+ , ADAMTS1 KO) were generated to
      investigate the direct causal role of ADAMTS1 in TAAD development. The incidence
      and rupture rates of BAPN-induced TAAD in ADAMTS1 KO mice were significantly
      lower than those in ADAMTS1flox/flox mice (45.5 versus 81.8% and 18.2 versus
      42.4%, respectively). Aortas from BAPN-treated ADAMTS1flox/flox mice displayed
      profound destruction of the elastic lamellae, abundant neutrophil and macrophage
      accumulation in the adventitia, obviously increased neutrophil proportions in
      peripheral blood and significantly increased expression of inflammatory factors
      in the early stage of TAAD induction, all of which were markedly suppressed in
      ADAMTS1 KO mice. Furthermore, ADAMTS1-deficient macrophages exhibited abrogated
      migration capacity both in vivo and in vitro. In conclusion, ADAMTS1 plays a
      crucial role in postnatal TAAD formation and rupture by regulating inflammatory
      responses, suggesting that ADAMTS1 might be a new therapeutic target for TAAD.

PMID- 30191629
TI  - Reliability and validity of last menstrual period for gestational age estimation
      in a low-to-middle-income setting.
AB  - AIM: Gestational age estimation by ultrasonography is the gold standard for
      dating pregnancies. However, the availability of prenatal ultrasonography in low
      to-middle-income countries is limited. This study aimed to assess the reliability
      and validity of last menstrual period (LMP) as a gestational age dating method
      among women in Johannesburg, South Africa. METHODS: A total of 741 pregnant women
      were enrolled into a longitudinal study (June 2013 to July 2016). Gestational age
      was determined by LMP and ultrasonography. Differences in ultrasound-based and
      LMP-based gestational age estimates were assessed according to the American
      College of Obstetrics and Gynecologists' guidelines and women were classified as
      having discrepant results or not. Multiple statistical analyses determined the
      level of agreement between the two methods and validity of LMP estimates.
      RESULTS: Compared to ultrasound, dating by LMP assessed gestational age as 0.2
      days longer. Women with discrepant results were of significantly lower weight and
      household socioeconomic status than those without discrepancies. While there was
      a substantial agreement (k = 0.64; 95% confidence interval, CI: 0.54, 0.71, P <
      0.001) between the two methods, LMP only had a 29.0% (95% CI: 14.2, 48.0)
      sensitivity in identifying late-term neonates and a 33.3% (95% CI: 4.33, 77.7)
      sensitivity in identifying post-term neonates. CONCLUSION: In the absence of
      ultrasound, LMP is a reliable alternative for gestational age dating during early
      pregnancy. However, it is not sensitive in identifying late- and post-term
      pregnancies and should not be relied upon to make clinical decisions regarding
      elective cesarean section or induction of labor for supposed prolonged
      pregnancies.

PMID- 30191631
TI  - New terminology for adverse events of fetal therapy: Re-evaluation of the thoraco
      amniotic shunting in a Japanese study.
AB  - AIM: Since fetal therapy has been newly developed, objective evaluation of
      adverse events (AE), all harmful events that are not always related to the
      procedures, has not yet been adequately reported. We established new terminology
      and tried to re-evaluate it based on the Japanese prospective thoraco-amniotic
      shunting (TAS) study. METHODS: From the literature, all complications that
      occurred with all fetal therapies were identified as a basis for developing the
      terminology. Grading was set from 0 to 5. Grade 3 was defined as the need for
      invasive treatment, such as surgery. Grade 4 was defined as life-threatening, and
      Grade 5 was defined as death of the mother or fetus. Then, one series of TAS that
      we had already reported was re-evaluated, including 24 cases with 37 procedures
      and 200 opportunities those could be evaluated AE after procedures. RESULTS:
      Grade 4 preterm rupture of the membranes was reported in only 1 of 24 cases.
      Catheter displacement was reported in 7, 2 and 11 cases, of Grades 1, 2 and 3,
      respectively. It was found that the double-basket catheter had some association
      with catheter displacement, but it was clear that there were no life-threatening
      AE. CONCLUSION: Newly developed AE criteria are now available for fetal therapy.
      They will contribute to the objective evaluation of AE of new fetal therapies in
      the future.

PMID- 30191633
TI  - Transvaginal cervicoisthmic cerclage for patients with extremely high-risk
      history of preterm delivery.
AB  - Transvaginal cervicoisthmic cerclage was carried out in 12 such patients who were
      at high-risk of premature delivery. Patients who underwent transvaginal
      cervicoisthmic cerclage had undergone conization, cervical radical hysterectomy
      or another form of extensive cervical resection, or had a history of third
      trimester miscarriage or premature delivery despite having previously undergone
      cervical cerclage several times for cervical incompetence. There were seven cases
      of pregnancy after extensive conization, and four had a history of failed
      cervical cerclage. Two of these cases were the same individual, who became
      pregnant twice after extensive conization and gave birth to a live infant each
      time. The mean age at surgery was 35.7 years, and cerclage was performed at 11-19
      weeks' gestation. All of the infants survived to hospital discharge. Transvaginal
      cervicoisthmic cerclage may be considered effective for patients with the history
      of recurring pregnancy loss due to previous failure of prophylactic cerclage.

PMID- 30191632
TI  - Comparison of the prognostic role of Q waves and inverted T waves in the
      presenting ECG of STEMI patients.
AB  - BACKGROUND: Both Q waves and T-wave inversion (TWI) in the presenting ECG are
      associated with a progressed stage of myocardial infarction, possibly with less
      potential for myocardial salvage with reperfusion therapy. Combining the
      diagnostic information from the Q- and T-wave analyses could improve the
      prognostic work-up in ST-elevation myocardial infarction (STEMI) patients.
      METHODS: We sought to determine the prognostic impact of Q waves and TWI in the
      admission ECG on patient outcome in STEMI. We formed four groups according to the
      presence of Q waves and/or TWI (Q+TWI+; Q-TWI+; Q+TWI-; Q-TWI-). We studied 627
      all-comers with STEMI derived from two patient cohorts. RESULTS: The patients
      with Q+TWI+ had the highest and those with Q-TWI- the lowest 30-day and one-year
      mortality. One-year mortality was similar between Q-TWI+ and Q+TWI-. The survival
      analysis showed higher early mortality in Q+TWI- but the higher late mortality in
      Q-TWI+ compensated for the difference at 1 year. The highest peak troponin level
      was found in the patients with Q+TWI-. CONCLUSION: Q waves and TWI predict
      adverse outcome, especially if both ECG features are present. Q waves and TWI
      predict similar one-year mortality. Extending the ECG analysis in STEMI patients
      to include both Q waves and TWI improves risk stratification.

PMID- 30191630
TI  - FGF9/FGFR2 increase cell proliferation by activating ERK1/2, Rb/E2F1, and cell
      cycle pathways in mouse Leydig tumor cells.
AB  - Fibroblast growth factor 9 (FGF9) promotes cancer progression; however, its role
      in cell proliferation related to tumorigenesis remains elusive. We investigated
      how FGF9 affected MA-10 mouse Leydig tumor cell proliferation and found that FGF9
      significantly induced cell proliferation by activating ERK1/2 and retinoblastoma
      (Rb) phosphorylations within 15 minutes. Subsequently, the expressions of E2F1
      and the cell cycle regulators: cyclin D1, cyclin E1 and cyclin-dependent kinase 4
      (CDK4) in G1 phase and cyclin A1, CDK2 and CDK1 in S-G2 /M phases were increased
      at 12 hours after FGF9 treatment; and cyclin B1 in G2 /M phases were induced at
      24 hours after FGF9 stimulation, whereas the phosphorylations of p53, p21 and p27
      were not affected by FGF9. Moreover, FGF9-induced effects were inhibited by MEK
      inhibitor PD98059, indicating FGF9 activated the Rb/E2F pathway to accelerate MA
      10 cell proliferation by activating ERK1/2. Immunoprecipitation assay and ChIP
      quantitative PCR results showed that FGF9-induced Rb phosphorylation led to the
      dissociation of Rb-E2F1 complexes and thereby enhanced the transactivations of
      E2F1 target genes, Cyclin D1, Cyclin E1 and Cyclin A1. Silencing of FGF receptor
      2 (FGFR2) using lentiviral shRNA inhibited FGF9-induced ERK1/2 phosphorylation
      and cell proliferation, indicating that FGFR2 is the obligate receptor for FGF9
      to bind and activate the signaling pathway in MA-10 cells. Furthermore, in a
      severe combined immunodeficiency mouse xenograft model, FGF9 significantly
      promoted MA-10 tumor growth, a consequence of increased cell proliferation and
      decreased apoptosis. Conclusively, FGF9 interacts with FGFR2 to activate ERK1/2,
      Rb/E2F1 and cell cycle pathways to induce MA-10 cell proliferation in vitro and
      tumor growth in vivo.

PMID- 30191634
TI  - Variations in fatty acid composition of Laoshan goat milk from partum to 135 days
      postpartum.
AB  - The objective of this study was to characterize the variations in fatty acid (FA)
      profile during 7 days of colostrum production and 5 months of mature milk
      production in Laoshan goats. The individual FA profiles of each sample were
      investigated by gas chromatography-mass spectrometry. Significant differences in
      FAs were found between colostrum and mature milk. The contents of saturated fatty
      acids (SFA), unsaturated fatty acids (UFA), monounsaturated fatty acids (MUFA),
      and polyunsaturated fatty acids (PUFA), and sum of C6, C8, and C10 (SC6+C8+C10 )
      were all significantly affected by lactation period. Furthermore, there was no
      significant difference in the ratio of UFA/SFA or C18:2 (cis9, cis12
      octadecadienoic acid)/C18:3 (all cis-9,12,15-octadecatrienoic acid) during the
      lactation period. The highest concentrations of SC6+C8+C10 , UFA, MUFA, and PUFA
      appeared in colostrum, but the highest SFA content was in mature milk. The
      highest proportions of SC6+C8+C10 and SFA were 11.32% and 79.55% on 5th day and
      135th day respectively. By contrast, the lowest proportion of UFA was 20.45% on
      the 135th day. C14:0 (10.93%-12.87%), C16:0 (27.54%-36.65%), C18:0 (10.47%
      14.59%), and C18:1 (18.80%-30.61%) were the most predominant FAs in goat milk
      with significant differences during the 135 days lactation period except C18:0.
      In conclusion, the results of this study suggest that the lactation time has a
      pronounced effect on the FA compositions of goat milk.

PMID- 30191635
TI  - The effect of antioxidants on Helicobacter pylori eradication: A systematic
      review with meta-analysis.
AB  - BACKGROUND: The efficacy and safety of the addition of antioxidants to triple or
      quadruple therapy were unclear. MATERIALS AND METHODS: This systematic review was
      performed in accordance with the PRISMA 2009 guidelines. A systematic search of
      PubMed, EMBASE, and the Cochrane Library databases was conducted to identify
      potentially relevant publications using the following keywords: ([Helicobacter
      pylori] or [H. pylori] or [Hp]) and ([antioxidant] or [vitamin] or [N
      acetylcysteine] or [curcumin] or [cranberry]). The primary end-point of this
      study was to evaluate the efficacy of the addition of antioxidants to triple or
      quadruple therapy according to ITT and PP analysis. The second end-points were
      side effects and the comparative efficacy in terms of H. pylori eradication
      according to different antioxidant and antibiotic combinations. RESULTS: We
      included 9 studies with 1260 participants. The total eradication rate of H.
      pylori in the group combining eradication therapy with antioxidants was not
      superior to that without antioxidants according to the ITT (pooled RR [95% CI] =
      1.17 [0.99-1.38]; P = 0.07) and PP analysis (pooled RR [95% CI] = 1.15 [0.99
      1.34; P = 0.07]. There were no differences regarding side effects between the two
      groups (pooled RR [95% CI], 1.36 [0.81-2.28]; P = 0.24). However, the eradication
      regimen with vitamin supplementation (1400 mg/day) showed a significant, superior
      efficacy in eradication relative to those without supplementation (pooled RR [95%
      CI] = 1.57 [1.35, 1.84]; P < 0.01). In particular, in the amoxicillin
      clarithromycin-based subgroup, the crude H. pylori eradication rate determined by
      ITT analysis was 81.3% and 68.6% for eradication therapy with and without
      antioxidant supplementation, respectively, which was a statistically significant
      difference (pooled RR [95% CI] = 1.23 [1.02-1.49]; P = 0.03). CONCLUSIONS: The
      addition of antioxidants (vitamin, N-acetylcysteine, curcumin, cranberry) to
      amoxicillin-clarithromycin-based therapy could improve the eradication rate, and
      vitamin supplementation might be effective at a high dosage. However, antioxidant
      supplements have no impact on improving side effects.

PMID- 30191637
TI  - Differences in use of electronic nicotine delivery systems by smoking status and
      demographic characteristics among Australian young adults.
AB  - ISSUE ADDRESSED: Electronic nicotine delivery systems (ENDS) continue to grow in
      popularity, particularly among young adults. Understanding by whom various ENDS
      are being used and why within this population segment can assist the development
      of appropriate interventions targeting those most vulnerable to use and inform
      policy decisions in this area. Accordingly, this study assessed the demographic
      characteristics associated with ENDS use among Australian young adults, and
      reasons for current e-cigarette use. METHODS: An online survey was administered
      to 1116 Australians aged 18-25 years (59% female). RESULTS: Smokers were more
      likely than non-smokers to report (a) ever use of ENDS (67% vs 28%), (b) ever use
      of an e-cigarette (64% vs 24%), e-cigar (17% vs 8%) or e-hookah (15% vs 8%) and
      (c) current use of e-cigarettes (19% vs 6%). Male smokers were more likely than
      female smokers to be current e-cigarette users. The most common reason for
      current e-cigarette use was enjoyment. CONCLUSIONS: Young male adults appear to
      be particularly vulnerable to becoming regular e-cigarette users. This
      demographic group may need to be a primary focus of prevention and intervention
      efforts. Contrary to popular belief, smoking cessation was not a primary reason
      for e-cigarette use. SO WHAT?: Greater efforts are needed to educate young adults
      on the harms associated with ENDS use, especially if use is being driven by the
      perception that they are a harmless means of amusement. Maintaining existing
      regulations limiting the accessibility of these products is crucial to ensuring
      widespread use is minimised.

PMID- 30191638
TI  - Value of top-hat procedure in management of squamous intraepithelial lesion.
AB  - AIM: To investigate the features of skip lesions and evaluate value of top-hat
      procedure in management of squamous intraepithelial lesion. METHODS: We reviewed
      the records of patients who underwent loop electrosurgical excision procedure
      (LEEP) in Peking University First Hospital between 2011 and 2016. Patients were
      confirmed to have CIN1-3. The term 'skip lesion' refers to lesion lying deep in
      cervical canal discontiguous with other lesions in transformation zone and was
      confirmed by top-hat. We compared their lesion grade in patients with or without
      skip lesion using logistic regression. We further reviewed patients who underwent
      subsequent hysterectomy within 6 months following LEEP and evaluated if top-hat
      procedure led to less residual lesions or was able to predict residual lesions.
      RESULTS: A total of 2260 patients were included and 595 underwent top-hat
      procedure. Thirty-nine out of 595 patients had skip lesions (6.5%), among whom
      two patients had CIN1 (5.1%), eight had CIN2 (20.5%) and 29 had CIN3 (74.4%).
      Logistical regression showed CIN3 was associated with higher risk of skip lesions
      compared to CIN1 (OR = 4.433, 95%CI: 1.036-18.964), while CIN2 was not (OR =
      1.762, 95%CI: 0.366-8.471). Sixty-two patients underwent hysterectomy within 6
      months following LEEP (CIN1-3), 24 underwent top-hat. Analysis revealed top-hat
      procedure did not result in less residual lesions. Colposcopy impression or prior
      HPV test was unable to predict skip lesions. CONCLUSION: About 9.4% patients with
      CIN3 had skip lesions in the study, which is associated with elevated risk for
      residual lesion. Top-hat procedure is able to detect skip lesions, but should not
      be performed on routinely because its prognostic value is not proved.

PMID- 30191636
TI  - Inhibition of kinesin family member 20B sensitizes hepatocellular carcinoma cell
      to microtubule-targeting agents by blocking cytokinesis.
AB  - Kinesin family member 20B (KIF20B, also known as MPHOSPH1) is a kinesin protein
      that plays a critical role in cytokinesis. Previously, we and others have
      demonstrated the oncogenic role of KIF20B in several cancers; however, the exact
      mechanisms underlying its tumorigenic effects remain unclear. Herein, we showed
      overexpression of KIF20B in human hepatocellular carcinoma (HCC) and reported a
      negative correlation between KIF20B level and prognosis of patients.
      Mechanistically, reducing KIF20B blockades mitotic exit of HCC cells at telophase
      in a spindle assembly checkpoint independent way. Importantly, reducing KIF20B
      acts synergistically with three microtubule-associated agents (MTA) to p53- or
      p14ARF-dependently suppress p53-wt or p53-null HCC cells. In addition to taxol,
      reducing KIF20B also enhanced the toxicity of two chemotherapeutic drugs,
      hydroxycamptothecin and mitomycin C. In conclusion, we found a novel mechanism in
      that blocking cytokinesis by KIF20B inhibition increases the efficacy of MTA; our
      results thus suggested a dual-mitotic suppression approach against HCC by
      combining MTA with KIF20B inhibition, which simultaneously blocks mitosis at both
      metaphase and telophase.

PMID- 30191641
TI  - Total Syntheses of Asperchalasines A-E.
AB  - The first total syntheses of asperchalasines A-E, a collection of unprecedented
      merocytochalasans, are reported. Aspochalasin B, a key tricyclic cytochalasan
      monomer, was first synthesized through a unified approach that hinges on a Diels
      Alder reaction and a ring-closing metathesis reaction. The bioinspired Diels
      Alder reactions of aspochalasin B with different epicoccine precursors were then
      explored, which enabled the divergent access of the heterodimers asperchalasines
      B-E as well as related congeners. Furthermore, the heterotrimer asperchalasine A
      was obtained from one epicoccine unit and two aspochalasin B units through a
      biomimetic Diels-Alder reaction followed by an oxidative [5+2]-cycloaddition.

PMID- 30191642
TI  - Enantioselective Functionalization of Enamides at the beta-Carbon Center with
      Indoles.
AB  - We report an enantioconvergent approach for the functionalization of enamides at
      the beta-carbon atom, which involves a chiral Bronsted acid induced
      tautomerization of 2-amidoallyl into 1-amidoallyl cations. These putative
      reactive intermediates were produced by ionization of racemic alpha-hydroxy
      enamides with a chiral Bronsted acid and captured with substituted indoles in a
      highly regio- and enantioselective manner.

PMID- 30191639
TI  - Hypoxia-inducible transgelin 2 selects epithelial-to-mesenchymal transition and
      gamma-radiation-resistant subtypes by focal adhesion kinase-associated insulin
      like growth factor 1 receptor activation in non-small-cell lung cancer cells.
AB  - Microenvironment, such as hypoxia common to cancer, plays a critical role in the
      epithelial-to-mesenchymal transition (EMT) program, which is a major route of
      cancer metastasis and confers gamma-radiation resistance to cells. Herein, we
      showed that transgelin 2 (TAGLN2), an actin-binding protein, is significantly
      induced in hypoxic lung cancer cells and that Snail1 is simultaneously increased,
      which induces EMT by downregulating E-cadherin expression. Forced TAGLN2
      expression induced severe cell death; however, a small population of cells
      surviving after forced TAGLN2 overexpression showed gamma-radiation resistance,
      which might promote tumor relapse and recurrence. These surviving cells showed
      high metastatic activity with an increase of EMT markers including Snail1. In
      these cells, TAGLN2 activated the insulin-like growth factor 1 receptor beta
      (IGF1Rbeta)/PI3K/AKT pathway by recruitment of focal adhesion kinase to the IGF1R
      signaling complex. Activation of the IGF1Rbeta/PI3K/AKT pathway also induced
      inactivation of glycogen synthase kinase 3beta (GSK3beta), which is involved in
      Snail1 stabilization. Therefore, both the IGF1Rbeta inhibitor (AG1024) and the
      PI3K inhibitor (LY294002) or AKT inactivation with MK2206 lower the cellular
      level of Snail1. Involvement of GSK3beta was also confirmed by treatment with
      lithium chloride, the inducer of GSK3beta phosphorylation, or MG132, the 26S
      proteasomal inhibitor, which also stabilized Snail1. In conclusion, the present
      study provides important evidence that hypoxia-inducible TAGLN2 is involved in
      the selection of cancer cells with enhanced EMT properties to overcome the
      detrimental environment of cancer cells.

PMID- 30191643
TI  - A Modular Approach to Sensitized Two-Photon Patterning of Photodegradable
      Hydrogels.
AB  - Photodegradable hydrogels have emerged as useful platforms for research on cell
      function, tissue engineering, and cell delivery as their physical and chemical
      properties can be dynamically controlled by the use of light. The photo-induced
      degradation of such hydrogel systems is commonly based on the integration of
      photolabile o-nitrobenzyl derivatives to the hydrogel backbone, because such
      linkers can be cleaved by means of one- and two-photon absorption. Herein we
      describe a cytocompatible click-based hydrogel containing o-nitrobenzyl ester
      linkages between a hyaluronic acid backbone, which is photodegradable in the
      presence of cells. It is demonstrated for the first time that by using a cyclic
      benzylidene ketone-based small molecule as photosensitizer the efficiency of the
      two-photon degradation process can be improved significantly. Biocompatibility of
      both the improved two-photon micropatterning process as well as the hydrogel
      itself is confirmed by cell culture studies.

PMID- 30191640
TI  - Tumor suppressive role for kinases phosphorylating p53 in DNA damage-induced
      apoptosis.
AB  - Tumor suppressor p53 plays an important role in cancer prevention. Under normal
      conditions, p53 is maintained at a low level. However, in response to various
      cellular stresses, p53 is stabilized and activated, which, in turn, initiates DNA
      repair, cell-cycle arrest, senescence and apoptosis. Post-translational
      modifications of p53 including phosphorylation, ubiquitination, and acetylation
      at multiple sites are important to regulate its activation and subsequent
      transcriptional gene expression. Particularly, phosphorylation of p53 plays a
      critical role in modulating its activation to induce apoptosis in cancer cells.
      In this context, previous studies show that several serine/threonine kinases
      regulate p53 phosphorylation and downstream gene expression. The molecular basis
      by which p53 and its kinases induce apoptosis for cancer prevention has been
      extensively studied. However, the relationship between p53 phosphorylation and
      its kinases and how the activity of kinases is controlled are still largely
      unclear; hence, they need to be investigated. In this review, we discuss various
      roles for p53 phosphorylation and its responsible kinases to induce apoptosis and
      a new therapeutic approach in a broad range of cancers.

PMID- 30191644
TI  - Comprehensive genetic screening: The prevalence of maturity-onset diabetes of the
      young gene variants in a population-based childhood diabetes cohort.
AB  - BACKGROUND: Maturity-onset diabetes of the young (MODY) is caused by autosomal
      dominant mutations in one of 13 confirmed genes. Estimates of MODY prevalence
      vary widely, as genetic screening is usually restricted based on clinical
      features, even in population studies. We aimed to determine prevalence of MODY
      variants in a large and unselected pediatric diabetes cohort. METHODS: MODY
      variants were assessed using massively parallel sequencing in the population
      based diabetes cohort (n = 1363) of the sole tertiary pediatric diabetes service
      for Western Australia (population 2.6 million). All individuals were screened,
      irrespective of clinical features. MODY variants were also assessed in a control
      cohort (n = 993). RESULTS: DNA and signed consent were available for 821
      children. Seventeen children had pathogenic/likely pathogenic variants in MODY
      genes, two diagnosed with type 2 diabetes, four diagnosed with antibody-negative
      type 1 diabetes (T1DM), three diagnosed with antibody-positive T1DM, and eight
      previously diagnosed with MODY. Prevalence of MODY variants in the sequenced
      cohort was 2.1%, compared to 0.3% of controls. CONCLUSIONS: This is the first
      comprehensive study of MODY variants in an unselected population-based pediatric
      diabetes cohort. The observed prevalence, increasing access to rapid and
      affordable genetic screening, and significant clinical implications suggest that
      genetic screening for MODY could be considered for all children with diabetes,
      irrespective of other clinical features.

PMID- 30191645
TI  - Dynamic Kinetic Asymmetric Reductive Amination: Synthesis of Chiral Primary beta
      Amino Lactams.
AB  - A highly efficient ruthenium-catalyzed asymmetric reductive amination (ARA) of
      racemic beta-keto lactams with molecular hydrogen and ammonium salts is disclosed
      for the synthesis of enantiomerically pure primary amino lactams through dynamic
      kinetic resolution (DKR). By this approach, a range of syn primary beta-amino
      lactams were obtained in high yields with high chemo-, enantio-, and
      diastereoselectivity (up to 98 % yield, 99 % ee, >20:1 d.r., syn products). The
      utility of the products has been demonstrated by rapid access to a key synthetic
      intermediate towards biologically active drug molecules. Meanwhile, mechanistic
      studies and control experiments indicate that the reaction may proceed through
      the hydrogenation of an iminium intermediate.

PMID- 30191646
TI  - Systemic bevacizumab for the treatment of chronic bleeding in hereditary
      haemorrhagic telangiectasia.
AB  - BACKGROUND: Hereditary haemorrhagic telangiectasia (HHT) is a rare hereditary
      multisystem vascular disorder causing visceral arteriovenous malformations and
      mucocutaneous bleeding. Chronic gastrointestinal bleeding and epistaxis often
      produce profound anaemia refractory to conventional treatment. Bevacizumab, an
      anti-vascular endothelial growth factor monoclonal antibody, may be effective in
      treatment of bleeding in HHT. METHODS: All HHT patients treated with systemic
      bevacizumab for chronic bleeding were selected for retrospective analysis. Data
      collected included demographics, baseline HHT characteristics, epistaxis grade,
      surgical interventions, bevacizumab dosing, adverse events, haemoglobin, red cell
      transfusions, intravenous iron infusions, and other anaemia and/or bleeding
      directed therapies. RESULTS: Thirteen HHT patients were treated with bevacizumab
      for a median of 13.9 (range 4.9-30.1) months. Compared with pretreatment values,
      bevacizumab treatment increased the mean haemoglobin by 4.0 g dL-1 (95% CI, 2.6
      5.3 g dL-1 ) [mean (95% CI) haemoglobin 8.5 (7.8, 9.9) g dL-1 vs. 12.5 (11.2,
      13.7) g dL-1 , P < 0.001)], reduced red cell units transfused by 92% [median of 6
      (range 0-59) units vs. 0 (range 0-15) units, P = 0.004] and reduced quantity of
      iron infused by 73% [mean (95% CI) 462 (257, 668) mg month-1 vs. 126 (75, 178) mg
      month-1 , P = 0.002]. Epistaxis control was achieved in 85% with bevacizumab
      versus 0% before treatment (P < 0.001). No patient required nasal or GI
      procedures during the maintenance period. Two patients (15%) developed grade 3
      hypertension requiring medical management. CONCLUSION: Systemic bevacizumab was
      highly effective to treat chronic bleeding in HHT. Further study is needed to
      confirm the magnitude of benefit and further define optimal dosing, treatment
      duration and long-term safety.

PMID- 30191647
TI  - Assessment of baroreflex sensitivity has no prognostic value in contemporary,
      optimally managed patients with mild-to-moderate heart failure with reduced
      ejection fraction: a retrospective analysis of 5-year survival.
AB  - OBJECTIVES: We evaluated the prognostic value of cardiac baroreflex sensitivity
      (BRS) in contemporary, optimally treated patients with mild-to-moderate heart
      failure with reduced ejection fraction (HFrEF). METHODS AND RESULTS: Data from 97
      patients with HFrEF (left ventricular ejection fraction 32 +/- 6%, all receiving
      angiotensin-converting enzyme inhibitor/angiotensin receptor blocker and beta
      blocker, 85% receiving aldosterone antagonist) were analysed retrospectively. All
      patients underwent standard clinical assessment, cardiopulmonary exercise testing
      and BRS evaluation with three methods: the phenylephrine (BRS-Phe), the sequence
      (BRS-Seq) and the controlled breathing (BRS-CtrBr) method. Data on 5-year all
      cause mortality and appropriate and documented implantable cardioverter
      defibrillator (ICD) discharges were collected. During a mean follow-up of 53 +/-
      15 months, the composite endpoint of all-cause death and appropriate and
      documented ICD discharge occurred in 31 (32%) patients. BRS measures assessed
      using all three methods were not related to survival in univariate Cox
      proportional hazards analyses (all P >0.25). There were also no differences in
      survival between low vs. preserved BRS groups, irrespective of the method used
      for BRS assessment (all P >=0.15). BRS-Phe correlated with several clinically
      important variables (including left ventricular ejection fraction: rS  = 0.27,
      and peak oxygen consumption: rS  = 0.32, both P < 0.05), while clinical
      associations of BRS-Seq and BRS-CtrBr were sparse. CONCLUSIONS: Assessment of
      cardiac BRS provides no prognostic information in the contemporary mild-to
      moderate HFrEF population receiving optimal management.

PMID- 30191648
TI  - Activation of protein phosphatase 1 by a selective phosphatase disrupting peptide
      reduces sarcoplasmic reticulum Ca2+ leak in human heart failure.
AB  - BACKGROUND: Disruption of Ca2+ homeostasis is a key pathomechanism in heart
      failure. CaMKII-dependent hyperphosphorylation of ryanodine receptors in the
      sarcoplasmic reticulum (SR) increases the arrhythmogenic SR Ca2+ leak and
      depletes SR Ca2+ stores. The contribution of conversely acting serine/threonine
      phosphatases [protein phosphatase 1 (PP1) and 2A (PP2A)] is largely unknown.
      METHODS AND RESULTS: Human myocardium from three groups of patients was
      investigated: (i) healthy controls (non-failing, NF, n = 8), (ii) compensated
      hypertrophy (Hy, n = 16), and (iii) end-stage heart failure (HF, n = 52).
      Expression of PP1 was unchanged in Hy but greater in HF compared to NF while its
      endogenous inhibitor-1 (I-1) was markedly lower expressed in both compared to NF,
      suggesting increased total PP1 activity. In contrast, PP2A expression was lower
      in Hy and HF compared to NF. Ca2+ homeostasis was severely disturbed in HF
      compared to Hy signified by a higher SR Ca2+ leak, lower systolic Ca2+ transients
      as well as a decreased SR Ca2+ load. Inhibition of PP1/PP2A by okadaic acid
      increased SR Ca2+ load and systolic Ca2+ transients but severely aggravated
      diastolic SR Ca2+ leak and cellular arrhythmias in Hy. Conversely, selective
      activation of PP1 by a PP1-disrupting peptide (PDP3) in HF potently reduced SR
      Ca2+ leak as well as cellular arrhythmias and, importantly, did not compromise
      systolic Ca2+ release and SR Ca2+ load. CONCLUSION: This study is the first to
      functionally investigate the role of PP1/PP2A for Ca2+ homeostasis in diseased
      human myocardium. Our data indicate that a modulation of phosphatase activity
      potently impacts Ca2+ cycling properties. An activation of PP1 counteracts
      increased kinase activity in heart failure and successfully seals the
      arrhythmogenic SR Ca2+ leak. It may thus represent a promising future
      antiarrhythmic therapeutic approach.

PMID- 30191649
TI  - Activity and outcomes of a cardio-oncology service in the United Kingdom-a five
      year experience.
AB  - AIMS: Cardio-oncology clinics optimise the cardiovascular status of cancer
      patients but there is a limited description of their structure, case mix,
      activity and results. The purpose of this paper is to describe the activity and
      outcomes of a cardio-oncology service, particularly with respect to supporting
      optimal cancer treatment and survival. METHODS AND RESULTS: We prospectively
      studied patients referred to our service from February 2011 to February 2016. New
      York Heart Association (NYHA) class and parameters of cardiac function were
      measured at baseline and after optimisation by our service. Up-titration of
      cardiac treatment, continuation of cancer therapy and mortality were used as
      outcome measures. Of the 535 patients (55.8% females) referred, rates of
      cardiotoxicity for anthracyclines, anti-HER2 agents and tyrosine kinase
      inhibitors were 75.8%, 69.8% and 62.1%, respectively. Patients with left
      ventricular systolic dysfunction (LVSD) (n =128) were younger, had higher rates
      of hypertension and previous exposure to chemotherapy/radiotherapy (P < 0.001).
      At a median follow-up of 360 days, 93.8% of the patients with LVSD showed
      improvement in left ventricular ejection fraction (45% pre vs. 53% post; P <
      0.001) and NYHA class (NYHA III-IV in 22% pre vs. 10% post; P = 0.01). All
      patients with normal left ventricular ejection fraction and biochemical or
      functional myocardial toxicity and 88% of patients with LVSD were deemed fit for
      continuation of cancer therapy after cardiovascular optimisation. CONCLUSIONS:
      Through the establishment of a cardio-oncology service, it is feasible to achieve
      high rates of cardiac optimisation and cancer treatment continuation.

PMID- 30191651
TI  - Recent changes to the Editorial Board.

PMID- 30191650
TI  - Family-focused practice with EASE: A practice framework for strengthening
      recovery when mental health consumers are parents.
AB  - This paper provides a framework for essential family-focused practices (EASE:
      Engage, Assess, Support, Educate) for clinicians to support parents with mental
      illness in the context of their family. The framework is underpinned by
      relational recovery as the parent/consumer's recovery is considered within the
      context of their relationships, including the relationship between clinician and
      parent/consumer. The central aim is to strengthen nurses' and other clinicians'
      capacity to address key psychosocial needs of parents and to strengthen
      relational recovery in families where parents have mental illness. The EASE
      framework is a theory and evidence-informed family practice approach to
      relational recovery within healthcare provision. The EASE practice components are
      defined and illustrated with practice exemplars that operationalize the framework
      within adult service settings. Potential applications and outcomes of using EASE
      are also described. The framework is intended as a practical guide for working
      with parents and families in inpatient and community mental health settings and
      may also be relevant for clinicians in a range of contexts including child
      welfare and primary health care.

PMID- 30191653
TI  - WEO Newsletter.

PMID- 30191652
TI  - Use of acetazolamide in the treatment of patients with refractory congestive
      heart failure.
AB  - AIMS: Optimal diuretic treatment of patients with refractory congestive heart
      failure (CHF) remains to be elucidated. In this work, we aimed to evaluate the
      serial changes of functional class and surrogates of fluid overload (weight and
      antigen carbohydrate 125) after addition of oral acetazolamide in patients with
      refractory CHF. Likewise, serial changes in renal function, serum electrolytes
      and pH were evaluated. METHOD: This is an observational retrospective study in
      which 25 ambulatory patients with refractory CHF that received acetazolamide in
      addition to standard intensive diuretic strategy were evaluated. Longitudinal
      assessment of New York Heart Association (NYHA) functional class and biomarkers
      was analyzed using joint modelling of longitudinal and survival data. RESULTS:
      All patients showed NYHA class III/IV at baseline. After prescription of
      acetazolamide, a total of 125 outpatient visits were recorded [median visits per
      patient: 6 (IQR = 3-7)] during a median follow-up of 152 days (IQR = 80-353). A
      significant decrease in NYHA class, weight, and antigen carbohydrate 125 was
      observed. On the other hand, estimated glomerular filtration rate increased over
      time. No significant changes in systolic blood pressure, serum sodium, potassium,
      amino-terminal pro-brain natriuretic peptide, and pH occurred. CONCLUSION: In a
      cohort of patients with refractory CHF treated with an intensive diuretic
      treatment, the addition of acetazolamide was associated with improvement in
      functional class and surrogates of fluid overload.

PMID- 30191654
TI  - Comparison of wounds' infection rate between tap water and normal saline
      cleansing: A meta-analysis of randomised control trials.

PMID- 30191655
TI  - Swedish translation and validation of the international skin tear advisory panel
      skin tear classification system.
AB  - The aims of this study were to translate the International Skin Tear Advisory
      Panel (ISTAP) classification system for skin tears into Swedish and to validate
      the translated system. The research process consisted of two phases. Phase I
      involved the translation of the classification system, using the forward-back
      translation method, and a consensus survey. The survey dictated that the best
      Swedish translation for "skin tear" was "hudfliksskada." In Phase 2, the
      classification system was validated by health care professionals attending a
      wound care conference held in the spring of 2017 in Sweden. Thirty photographs
      representing three types of skin tear were presented to participants in random
      order. Participants were directed to classify the skin tear types in a data
      collection sheet. The results indicated a moderate level of agreement on
      classification of skin tears by type. Achieving moderate agreement for the ISTAP
      skin tear tool is an important milestone as it demonstrates the validity and
      reliability of the tool. Skin tear classification typing is a complex skill that
      requires training and time to develop. More education is required for all health
      care specialists on the classification of skin tears.

PMID- 30191657
TI  - Maternal control of seed weight in rapeseed (Brassica napus L.): the causal link
      between the size of pod (mother, source) and seed (offspring, sink).
AB  - Seed size/weight is one of the key traits related to plant domestication and crop
      improvement. In rapeseed (Brassica napus L.) germplasm, seed weight shows
      extensive variation, but its regulatory mechanism is poorly understood. To
      identify the key mechanism of seed weight regulation, a systematic comparative
      study was performed. Genetic, morphological and cytological evidence showed that
      seed weight was controlled by maternal genotype, through the regulation of seed
      size mainly via cell number. The physiological evidence indicated that
      differences in the pod length might result in differences in pod wall
      photosynthetic area, carbohydrates and the final seed weight. We also identified
      two pleiotropic major quantitative trait loci that acted indirectly on seed
      weight via their effects on pod length. RNA-seq results showed that genes related
      to pod development and hormones were significantly differentially expressed in
      the pod wall; genes related to development, cell division, nutrient reservoir and
      ribosomal proteins were all up-regulated in the seeds of the large-seed pool.
      Finally, we proposed a potential seed weight regulatory mechanism that is
      specific to rapeseed and novel in plants. The results demonstrate a causal link
      between the size of the pod (mother, source) and the seed (offspring, sink) in
      rapeseed, which provides novel insight into the maternal control of seed weight
      and will open a new research field in plants.

PMID- 30191656
TI  - Expression of interferon-stimulated gene 15-kDa protein, cyclooxygenase (COX) 1,
      COX-2, aldo-keto reductase family 1, member B1, and prostaglandin E synthase in
      the spleen during early pregnancy in sheep.
AB  - The spleen is a unique lymphoid organ that plays a key role in immune regulation.
      Interferon-tau induces upregulation of interferon-stimulated gene 15-kDa protein
      (ISG15) in the uterus during early pregnancy in sheep. Prostaglandins (PGs) have
      important effects in both the activation and the inhibition of immune response
      through an autocrine and paracrine manner. In this study, splenic samples were
      obtained at Day 16 of the estrous cycle, and Days 13, 16, and 25 of pregnancy
      from ewes, and the expression of ISG15 and PG synthases, including cyclooxygenase
      1 (COX-1), COX-2, PGE synthase (PTGES), and PGF synthase (aldo-keto reductase
      family 1, member B1, AKR1B1), was detected through quantitative real-time PCR,
      western blot, and immunohistochemistry analysis. Our results showed that there
      was upregulation of COX-2 mRNA and protein at Day 25 of pregnancy, and ISG15 mRNA
      and conjugated proteins, and AKR1B1 mRNA and dimer at Days 16 and 25 of
      pregnancy. COX-2 and AKR1B1 proteins were limited to the capsule, trabeculae, and
      splenic cords. However, the expression of COX-1 and PTGES was not affected by
      early pregnancy. In conclusion, ISG15-conjugated proteins, COX-2 and AKR1B1
      upregulated in maternal spleen during early pregnancy, which may be beneficial
      for the placentation in sheep.

PMID- 30191658
TI  - Rational Design Principles for the Transport and Subcellular Distribution of
      Nanomaterials into Plant Protoplasts.
AB  - The ability to control the subcellular localization of nanoparticles within
      living plants offers unique advantages for targeted biomolecule delivery and
      enables important applications in plant bioengineering. However, the mechanism of
      nanoparticle transport past plant biological membranes is poorly understood.
      Here, a mechanistic study of nanoparticle cellular uptake into plant protoplasts
      is presented. An experimentally validated mathematical model of lipid exchange
      envelope penetration mechanism for protoplasts, which predicts that the
      subcellular distribution of nanoparticles in plant cells is dictated by the
      particle size and the magnitude of the zeta potential, is advanced. The mechanism
      is completely generic, describing nanoparticles ranging from quantum dots, gold
      and silica nanoparticles, nanoceria, and single-walled carbon nanotubes (SWNTs).
      In addition, the use of imaging flow cytometry to investigate the influence of
      protoplasts' morphological characteristics on nanoparticle uptake efficiency is
      demonstrated. Using DNA-wrapped SWNTs as model nanoparticles, it is found that
      glycerolipids, the predominant lipids in chloroplast membranes, exhibit stronger
      lipid-nanoparticle interaction than phospholipids, the major constituent in
      protoplast membrane. This work can guide the rational design of nanoparticles for
      targeted delivery into specific compartments within plant cells without the use
      of chemical or mechanical aid, potentially enabling various plant engineering
      applications.

PMID- 30191660
TI  - A novel method for assessing patients with schizophrenia and their first-degree
      relatives by increasing cognitive load of visuo-spatial working memory.
AB  - INTRODUCTION: In patients with schizophrenia, social and functional outcome is
      determined by the cognitive impairment. Assessment of visuo-spatial working
      memory (VSWM) which can simulate the day-to-day activities by simultaneous
      involvement of various elements of working memory may reflect disorganized
      thinking and fragmentation of thoughts in schizophrenia. METHODS: Thirty-six
      patients with schizophrenia, 29 first-degree relatives of patients, and 25
      healthy controls performed a VSWM task with three memory loads (comprising three
      pairs, six pairs, and eight pairs of abstract pictures). They were administered
      Hindi version of the Mini Mental State Examination, Scale for the Assessment of
      Negative Symptoms and Scale for the Assessment of Positive Symptoms, and
      Edinburgh handedness inventory. RESULTS: Patients (mean age 27.29(5.98) years)
      committed significantly higher number of errors than healthy controls (mean age
      26.76(6.08) years) in load 3 (P = 0.012) and total errors (P = 0.018). Within all
      the groups, errors in load 3 were significantly higher than in load 2.
      Significant correlation was observed between years of education (r = -0.388, P =
      0.021), treatment duration (r = -0.880, P < 0.001), negative symptoms scores (r =
      0.345, P = 0.039), and the total errors committed by patients. DISCUSSION: Visuo
      spatial working memory was impaired in schizophrenia with increasing cognitive
      load with no difference in search time between the groups.

PMID- 30191659
TI  - Cardiovascular, cancer and mortality events after bariatric surgery in people
      with and without pre-existing diabetes: A nationwide study.
AB  - BACKGROUND: Bariatric surgery reduces cardiovascular events and mortality risk in
      obese individuals. However, it is unclear whether diabetes modifies this effect.
      This study examined mortality, cardiovascular, and cancer risk following
      bariatric surgery in adults with and without pre-existing diabetes. METHODS:
      Using mortality-linked Hospital Episodes Statistics (2006-14) from England, the
      risk of death, myocardial infarction, stroke, unstable angina, heart failure, and
      cancer following bariatric surgery was examined; the risk of death in people
      undergoing surgery was also compared with mortality rates of the general
      population. RESULTS: Of the 35 887 people undergoing bariatric surgery, 9175
      (25.6%) had pre-existing diabetes. During a mean follow-up of 5.3 years, 801
      people died, of whom 293 (36.6%) had pre-existing diabetes. The risk of all-cause
      mortality was 26% higher in people with than without diabetes (adjusted hazard
      ratio [aHR] 1.26, 95% confidence interval [CI] 1.08-1.46), whereas the risk of
      cancer was 21% higher (aHR 1.21; 95% CI 1.14-1.77). The risk of cardiovascular
      events was higher for patients with than without diabetes (aHRs [95% CIs] 2.08
      [1.42-3.05], 1.80 [1.29-2.52], 1.61 [1.18-2.19], and 1.42 [1.14-1.77] for
      myocardial infarction, unstable angina, stroke, and heart failure, respectively).
      Compared with the general population, the age-standardized mortality rate ratio
      was 1.70 (1.52-1.91) and 1.35 (1.23-1.48) in people with and without pre-existing
      diabetes, respectively. CONCLUSIONS: For patients with pre-existing diabetes, the
      risk of death, cardiovascular events, and cancer after bariatric surgery was
      higher than for those without diabetes, whose mortality risk after surgery
      remains 35% higher than that of the general population.

PMID- 30191662
TI  - The developmental and genetic trajectory of coloration in the guppy (Poecilia
      reticulata).
AB  - Examining the association between trait variation and development is crucial for
      understanding the evolution of phenotypic differences. Male guppy ornamental
      caudal fin coloration is one trait that shows a striking degree of variation
      within and between guppy populations. Males initially have no caudal fin
      coloration, then gradually develop it as they reach sexual maturity. For males,
      there is a trade-off between female preference for caudal fin coloration and
      increased visibility to predators. This trade-off may reach unique endpoints in
      males from different predation regimes. Caudal fin coloration includes black
      melanin, orange/yellow pteridines or carotenoids, and shimmering iridescence.
      This study examined the phenotypic trajectory and genetics associated with color
      development. We found that black coloration always developed first, followed by
      orange/yellow, then iridescence. The ordering and timing of color appearance was
      the same regardless of predation regime. The increased expression of melanin
      synthesis genes correlated well with the visual appearance of black coloration,
      but there was no correlation between carotenoids or pteridine synthesis gene
      expression and the appearance of orange/yellow. The lack of orange/yellow
      coloration in earlier male caudal fin developmental stages may be due to reduced
      expression of genes underlying the development of orange/yellow xanthophores.

PMID- 30191661
TI  - Chronic simian immunodeficiency virus infection is associated with contrasting
      phenotypes of dysfunctional Bcl6+ germinal center B cells or Bcl6- Bcl2+ non
      germinal center B cells.
AB  - Human immunodeficiency virus (HIV) infection is characterized by dysfunctional B
      cell responses. Here we show that chronic simian immunodeficiency virus (SIV)
      infection is characterized by an expansion of either lymph node germinal center
      (GC) B cells that co-express Bcl6, Ki-67 and IL-21R and correlate with expanded T
      follicular helper (Tfh) cells or B cells that lack Bcl6, Ki-67 and IL-21R but
      express high levels of anti-apoptotic Bcl2 that negatively correlate with Tfh
      cells. The lack of Tfh cells likely contributes to persistence of dysfunctional
      non-proliferating B cells during chronic infection. These findings have
      implications for protective immunity in HIV-infected individuals who harbour low
      frequencies of Tfh cells.

PMID- 30191663
TI  - Neurodevelopmental outcomes at 2 and 4 years in children with congenital heart
      disease.
AB  - BACKGROUND AND OBJECTIVES: Children with congenital heart disease (CHD) are at
      risk for neurodevelopmental (ND) delays. The purpose of this study is to compare
      the ND testing results of children with CHD at 2 and 4 years of age and determine
      if rates of ND delays change over time. METHODS: Children with CHD completed the
      Bayley Scales of Infant Development-III (BSID-III) at 2 years of age, and
      standardized neuropsychological measures at 4 years. Scores were compared with
      test norms and were classified as: average (within one SD of test mean); at risk
      (1-2 SDs from the test mean); and delayed (>2 SD from test mean). Pearson
      correlations and McNemar's exact tests were performed to determine the
      relationship between test scores at the two times of assessment. RESULTS: Sixty
      four patients completed evaluations at 24 +/- 3 months of age and 4 years of age.
      BSID-III cognitive and fine motor scores were correlated with preschool IQ and
      fine motor scores, r = .75 to .87, P < .0001. Agreement in score categories was
      79% for cognitive and 61% for fine motor. More patients had at risk or delayed
      scores at age 4 vs age 2 (P <= .01). CONCLUSION(S): Despite significant
      correlations between 2- and 4-year-old test scores, many patients who scored in
      the average range at age 2 showed deficits at age 4. BSID-III scores at age 2 may
      underestimate delays. Therefore, longitudinal ND assessment is recommended.

PMID- 30191664
TI  - Metformin administration attenuates dipeptidyl peptidase-4 inhibitor-induced
      increases in Krebs von den Lungen-6 (KL-6) levels.

PMID- 30191665
TI  - Repeated assessments of physical activity and risk of incident venous
      thromboembolism.
AB  - Essentials It is debated whether physical activity influences the risk of venous
      thromboembolism. The association was explored accounting for fluctuations in
      physical activity over time. Overall and in the elderly, physical activity was
      associated with 23% and 30% lower risk. A moderate proportion of the association
      (14-36%) was mediated via body mass index. SUMMARY: Background Whether physical
      activity influences the risk of incident venous thromboembolism (VTE) remains
      controversial, potentially because of methodological challenges, such as
      regression dilution bias. Objectives To investigate whether physical activity was
      associated with VTE risk, and explore the role of body mass index (BMI) as a
      mediator in a population-based cohort with repeated assessments of physical
      activity. Methods Participants (n = 30 002) attending one or more surveys of the
      Tromso Study 4-6 (1994-1995, 2001-2002, and 2007-2008) were included and
      categorized on the basis of weekly physical activity. Incident VTE was registered
      until 31 December 2016. Hazard ratios (HRs) were calculated by the use of time
      varying Cox regression models. The Aalen additive hazard model was used to
      quantify the total, direct and indirect effects of physical activity. Results
      There were 531 incident VTEs during follow-up. Physical activity (>= 1 per week)
      was associated with a lower risk of VTE (HR 0.77, 95% confidence interval [CI]
      0.64-0.92) than being inactive. The effect was most pronounced for those aged >=
      65 years (HR 0.70, 95% CI 0.55-0.88) and for provoked events (HR 0.66, 95% CI
      0.50-0.89). The differences in absolute risk between active and inactive
      individuals were - 0.42 (95% CI - 0.73 to - 0.14) and - 1.59 (95% CI - 2.74 to -
      0.52) events annually per 1000 individuals in the total and elderly populations,
      respectively. A moderate proportion of the association (14-36%) was mediated via
      BMI. Conclusion Our findings suggest that regular physical activity is associated
      with a lower risk of VTE, particularly in the elderly. The association occurred
      at a low weekly amount of physical activity, and was only partly mediated by BMI.

PMID- 30191667
TI  - MicroRNA-130a inhibits spermatogenesis by directly targeting androgen receptor in
      mouse Sertoli cells.
AB  - MicroRNAs (miRNAs) have been shown to play a key role in spermatogenesis.
      However, whether the miRNAs influence androgen/androgen receptor (AR) signaling
      during spermatogenesis remains unclear. Using a bioinformatic approach, a
      potential miRNA, miR-130a, which could bind to Ar-3'untranslated region directly
      was identified. The expression pattern of miR-130a was further characterized by
      quantitative real-time polymerase chain reaction. It was found that miR-130a was
      abundant in testis and its expression level was negatively correlated with age.
      Overexpression of miR-130a could inhibit AR expression both in vitro and in vivo.
      Moreover, the mice with an intratesticular injection of miR-130a showed defects
      in spermatogenesis and increased germ cell apoptosis. Taken together, these
      results suggest that miR-130a could negatively regulate AR expression in mouse
      Sertoli cell, which further cause defects in spermatogenesis.

PMID- 30191666
TI  - A meta-analysis of MitraClip combined with medical therapy vs. medical therapy
      alone for treatment of mitral regurgitation in heart failure patients.
AB  - AIMS: Survival benefit of percutaneous mitral valve repair with the MitraClip
      over conservative treatment of functional mitral regurgitation (MR) remains
      unclear. The purpose of this meta-analysis is to compare survival outcomes of
      MitraClip with those of medical therapy in patients with functional MR. METHODS
      AND RESULTS: A comprehensive literature search of PubMed, MEDLINE, and Google
      Scholar was conducted including studies evaluating MitraClip vs. medical therapy
      with multivariate adjustment and with >80% of patients with functional MR. Death
      from any cause was the primary endpoint, while freedom from readmission was the
      secondary one, evaluated with random effects. These analyses were performed at
      study level and at patient level including only functional MR when available,
      evaluating the effect of MitraClip in different subgroups according to age,
      ischaemic aetiology, presence of implantable cardioverter defibrillator/cardiac
      resynchronization therapy, and left ventricular ejection fraction and volumes. We
      identified six eligible observational studies including 2121 participants who
      were treated with MitraClip (n = 833) or conservative therapy (n = 1288).
      Clinical follow-up was documented at a median of 400 days. At study-level
      analysis, MitraClip, when compared with medical therapy (P = 0.005), was
      associated with significant reduction of death (P = 0.002) and of readmission due
      to cardiac disease. At patient-level analysis, including 344 patients, MitraClip
      confirmed robust survival benefit over medical therapy for all patients with
      functional MR and among the most important subgroups. CONCLUSIONS: Compared with
      conservative treatment, MitraClip is associated with a significant survival
      benefit. Importantly, this superiority is particularly pronounced among patients
      with functional MR and across all the main subgroups.

PMID- 30191668
TI  - A Comparative Evaluation of Stress Distribution with Two Attachment Systems of
      Varying Heights in a Mandibular Implant-Supported Overdenture: A Three
      Dimensional Finite Element Analysis.
AB  - PURPOSE: To analyze and compare the stress distribution in an implant-retained
      overdenture complex using ball and Locator attachments of three heights by means
      of a 3D finite element analysis (FEA). MATERIALS AND METHODS: Six finite element
      models comprising an edentulous mandible with two interforaminal bone-level
      implants and ball attachments of heights 1 mm (A1), 3 mm (A3), and 5 mm (A5), and
      Locator attachments of heights 1 mm (B1), 3 mm (B3), and 5 mm (B5), were designed
      using ANSYS Workbench Software. Unilateral vertical (100 N) and oblique loads
      (100 N at 30 degrees  to the longitudinal axis of the implant in buccolingual
      direction) were applied. Average von Mises stress values were evaluated
      quantitatively and qualitatively. RESULTS: Locator attachments showed lower
      stress values as compared to the ball attachments in all examined areas. The
      increase in the height of both resulted in increased stress values. Higher values
      were observed at the implant neck in all models, as compared to the body and the
      apex. The recorded stress was higher in the cortical bone as compared to the
      cancellous bone. CONCLUSIONS: Within the limitations of the study, Locator
      attachments demonstrated lesser and more homogenous stress distribution in the
      implant-overdenture complex in comparison to ball attachments. The stresses
      generated within the tissues increase with an increase in collar height of the
      attachment system and therefore, attachments should be as short as possible for
      more favorable stress transmission.

PMID- 30191669
TI  - Motivators of adherence to integrated management among patients with chronic
      kidney disease: A qualitative study.
AB  - The integrated management of chronic kidney disease (CKD) demands significant
      changes, as patients need to adhere to dialysis, medication, and dietary and
      fluid restrictions. Therefore, there is a need to identify the motivators of
      adherence to improve the quality of life of these patients. The aim of the
      present study was to explore the motivators of adherence to integrated management
      among patients with CKD in South Africa. A phenomenological design was used. A
      sample size of 12 participants was selected according to data saturation. The
      purposive sampling method was used to select the participants. Data were
      collected with the help of a semistructured interview schedule developed from the
      literature. A thematic framework analysis was conducted to identify the
      motivators of adherence to integrated management; these were found to be family
      support, anxiety about eligibility for kidney transplant, support of other
      patients, awareness of complications associated with non-adherence to integrated
      management, and fear of being removed from the CKD program. Identified motivators
      could be used to develop specific interventions that address or foster adherence
      behavior as a requirement for integrated management.

PMID- 30191670
TI  - Nebulization as a Tool for Photosensitizer Delivery to the Respiratory Tract.
AB  - To this day, any photosensitizers for the photodynamic treatment of pulmonary
      illnesses have been administered intravenously. There is, however, an intrinsic
      difficulty in reaching the target cells or bacteria in the respiratory system.
      Nebulization could overcome distribution problems and alleviate side effects by
      delivering the photosensitizers directly to the lungs. In this study, we
      evaluated the viability of three photosensitizers (indocyanine green, the
      chlorine Photodithazine(r), and the porphyrin Photogem(r)) was evaluated
      comparatively in a jet nebulizer. Quantitative analysis was performed by looking
      at the droplet size, extent of nebulization, output over time, and stability of
      the solutions. All of the tested photosensitizers were found to be adequately
      nebulized. We also demonstrated the delivery of indocyanine green to the
      pulmonary tract and its activation with infrared light in a murine model using
      extracorporeal detection of fluorescence. This was an important step towards
      clinical implementation of the extracorporeally-illuminated photodynamic
      inactivation of pneumonia, recently demonstrated in vivo by this research group.
      This article is protected by copyright. All rights reserved.

PMID- 30191672
TI  - Eliciting imitation in early infancy.

PMID- 30191671
TI  - Restraint interventions in people with moderate to profound intellectual
      disabilities: Perspectives of support staff and family members.
AB  - BACKGROUND: Due to incompatibilities in communication, it is key that family
      members and support staff can take the perspective of people with moderate to
      profound intellectual disabilities (ID) whilst putting aside their own
      perspectives. METHOD: Ten vignettes describing types of restraint interventions
      (RIs) were presented to 20 unique pairs of support staff and family members
      related to individuals with moderate to profound ID. RESULTS: In taking their own
      perspective, more than half of the support staff and family members perceived all
      RIs as involuntary and severe. In contrast, when asked to put themselves in the
      position of the client/family member, only three RIs were considered involuntary
      by a majority of support staff and family members. CONCLUSIONS: These results
      indicate that support staff and family members can take into account the
      perspective of people with moderate to profound ID in the evaluation and
      consideration of involuntary care.

PMID- 30191673
TI  - Evaluation of a quantitative serum Aspergillus fumigatus-specific IgM assay for
      diagnosis of chronic pulmonary aspergillosis.
AB  - BACKGROUND: The early diagnosis of chronic pulmonary aspergillosis (CPA) remains
      challenging. Currently, a new quantitative IgM antibody assay that enveloped
      purified galactomannan extracted from Aspergillus fumigatus as antigen was
      commercially available in China, but its diagnostic value remains to be
      established. METHODS: To evaluate the role of this commercial IgM assay for
      diagnosis of CPA, a multi-center prospective study was performed in 12 hospitals
      in Zhejiang Province, from January 1 to December 31, 2016. Adult inpatients
      without severe immunocompromised condition and those with persistent clinical
      symptoms/radiological findings >=3 months or a consistent appearance in chest CT
      that was suggestive of CPA were included. The clinical data were compiled using a
      structured questionnaire. RESULTS: A total of 87 cases were enrolled, including
      43 CPA. The sensitivity ranged from 16.3% to 46.5%, and the specificity from
      77.3% to 95.5% when cutoffs were from 50 to 80 arbitrary unit (AU)/mL. The
      receiver operating characteristic analysis revealed an area under the curve of
      0.627. When a cutoff of 38.12 AU/mL was applied, the sensitivity and specificity
      were 69.8% and 56.8%, respectively, which represents the best performance.
      CONCLUSIONS: To our knowledge, this study was the first to evaluate this
      commercial A. fumigatus-specific IgM antibody assay in CPA patients in China and
      indicates that this IgM assay has a limited value and should not be a prior
      recommendation for CPA diagnosis.

PMID- 30191674
TI  - The Potential Role of Synanthropic Rodents and Flies in the Transmission of
      Enterocytozoon bieneusi on a Dairy Cattle farm in China.
AB  - Enterocytozoon bieneusi causes microsporidiosis, a condition with complex
      epidemiology involving both direct and indirect transmission routes. To assess
      the potential role of synanthropic rodents and flies in the transmission of this
      pathogen, a total of 277 cattle fecal samples, 199 synanthropic rodents, and 50
      batches of 20 flies were collected from a cattle farm. These samples were
      screened for the presence of E. bieneusi by PCR and sequencing of the internal
      transcribed spacer (ITS) region of the rRNA gene. The positive rates of cattle,
      synanthropic rodents, and flies were 11.9% (33/277), 4.0% (8/199) and 12.0%
      (6/50), respectively. Nineteen genotypes were identified, including 11 known
      genotypes (BEB6, I, COS-I, EbpC, D, J, CHS5, CHG1 to CHG3 and CHG14) and eight
      novel genotypes (named CHC9 to CHC16). The dominant genotype detected in the
      present study, BEB6, was found in all three categories of hosts. Moreover, human
      pathogenic genotypes D and EbpC were also observed in both synanthropic rodents
      and flies. These results demonstrate that synanthropic rodents and flies may act
      as biological disseminator or mechanical vector in the transmission of
      microsporidiosis to humans. Efforts should be made to minimize threats from these
      commensal animals to public health.

PMID- 30191675
TI  - Changes to the core and flanking sequences of G-box elements lead to increases
      and decreases in gene expression in both native and synthetic soybean promoters.
AB  - Cis-regulatory elements in promoters are major determinants of binding
      specificity of transcription factors (TFs) for transcriptional regulation. To
      improve our understanding of how these short DNA sequences regulate gene
      expression, synthetic promoters consisting of both classical (CACGTG) and variant
      G-box core sequences along with different flanking sequences derived from the
      promoters of three different highly expressing soybean genes, were constructed
      and used to regulate a green fluorescent protein (gfp) gene. Use of the classical
      6-bp G-box provided information on the base level of GFP expression while
      modifications to the 2-4 flanking bases on either side of the G-box influenced
      the intensity of gene expression in both transiently transformed lima bean
      cotyledons and stably transformed soybean hairy roots. The proximal 2-bp
      sequences on either flank of the G-box significantly affected G-box activity,
      while the distal 2-bp flanking nucleotides also influenced gene expression albeit
      with a decreasing effect. Manipulation of the upstream 2- to 4-bp flanking
      sequence of a G-box variant (GACGTG), found in the proximal region of a
      relatively weak soybean glycinin promoter, significantly enhanced promoter
      activity using both transient and stable expression assays, if the G-box variant
      was first converted into a classical G-box (CACGTG). In addition to increasing
      our understanding of regulatory element composition and structure, this study
      shows that minimal targeted changes in native promoter sequences can lead to
      enhanced gene expression, and suggests that genome editing of the promoter region
      can result in useful and predictable changes in native gene expression.

PMID- 30191676
TI  - Optimizing band selection for spectral detection of Aphis glycines Matsumura in
      soybean.
AB  - BACKGROUND: Soybean aphid, Aphis glycines Matsumura (Hemiptera: Aphididae), is a
      significant insect pest of soybean in North America. Accurate estimation of A.
      glycines densities requires costly, time-intensive weekly counts of adults and
      nymphs on plants. Field studies were conducted in 2013 and 2014 to assess the
      potential for spectral-based remote sensing to more efficiently quantify
      cumulative aphid-days (CADs) using soybean canopy reflectance. RESULTS: Narrow
      band wavelengths in the near-infrared spectral range were associated with CAD,
      but those in the visible spectral range were not associated with CAD. Simple
      linear regression models of CAD on reflectance were generally better than
      quadratic and cubic regression models. Simulated wide-band sensors centered at
      740-1100 nm yielded better regression models than ones centered at 600-740 nm,
      regardless of bandwidth. Among the simulated wide-band sensors, increasing sensor
      bandwidth worsened CAD estimation or required more simulated sensors to optimize
      CAD estimation. Optimal combinations of spectral bands explained 83-96% of the
      experimentally manipulated variation in CAD. CONCLUSION: Near-infrared
      wavelengths at 780 +/- 50 nm can effectively estimate A. glycines abundance on
      soybean. Our approach of simulating wide-band multispectral sensors from ground
      based hyperspectral data helped to refine spectral sensors and holds potential to
      reduce the cost and complexity of treat/no-treat classification tasks. This study
      will contribute to future research aiming to quantify insect injury using
      customized commercial-grade sensors for detection, quantification, and
      differentiation of A. glycines from other stressors. (c) 2018 Society of Chemical
      Industry.

PMID- 30191677
TI  - High frequency of CD74 expression in lymphomas: implications for targeted therapy
      using a novel anti-CD74-drug conjugate.
AB  - CD74 is a type II transmembrane glycoprotein that functions as an MHC class II
      chaperone and displays diverse roles in immune responses. Recently, anti-CD74
      immunotherapy has shown promise as an effective treatment strategy for lymphoid
      neoplasms in preclinical models. Using a human anti-CD74 antibody (SP7219), we
      defined the expression of CD74 protein in both normal and over 790 neoplastic
      hematolymphoid tissue samples. We found that CD74 is expressed broadly in normal
      B-cell compartments including primary and secondary lymphoid follicles and in the
      thymic medulla. The vast majority of lymphomas expressed CD74, including Hodgkin
      lymphomas (98%), B-cell lymphomas (96%), extranodal NK/T-cell lymphomas (88%),
      mature T-cell lymphomas (80%), and plasma cell myeloma (75%). Our findings
      confirm and expand previous observations regarding the expression of CD74 and
      suggest that CD74 expression on tumor cells may be directly targeted for
      immunomodulatory therapy for lymphoid and plasma cell malignancies.

PMID- 30191678
TI  - Do Calcium-based Phosphate binders Accelerate or Prevent Coronary Artery
      Calcification in Dialysis Patients?

PMID- 30191679
TI  - Gallic acid attenuates allergic airway inflammation via suppressed interleukin-33
      and group 2 innate lymphoid cells in ovalbumin-induced asthma in mice.
AB  - BACKGROUND: Asthma is an inflammatory disease characterized by airway
      hyperresponsiveness. Gallic acid is a powerful anti-inflammatory agent. In this
      study we aimed to investigate the efficacy of gallic acid in asthma treatment and
      its mechanisms. METHODS: An ovalbumin-induced asthma mouse model was generated.
      Pro-inflammatory cell infiltration and T helper (Th2)-associated cytokine release
      in the bronchoalveolar lavage fluid (BALF) were analyzed to reflect the severity
      of asthma in mice. An interleukin-33 (IL-33)-induced asthma mouse model was also
      generated to study the mechanism by which gallic acid could improve asthma. Group
      2 lymphoid cells (ILC2s) were identified using flow cytometry. Proteins were
      detected using Western blotting. RESULTS: Ovalbumin significantly increased the
      infiltration of pro-inflammatory cells, including eosinophils, macrophages,
      lymphocytes, and neutrophils, accompanied by enhanced airway hyperesponsiveness.
      Gallic acid reduced pro-inflammatory cell infiltration and improved airway
      hyperresponsiveness. Meanwhile, gallic acid reduced IL-5 and IL-13 levels in BALF
      and decreased expression of IL-33 in the lungs. Mechanistically, gallic acid
      inhibited MyD88 expression and downregulated nuclear factor (NF)-kappaB signaling
      to decrease IL-33 expression. CONCLUSIONS: Gallic acid can mollify ovalbumin
      induced asthma in mice, possibly by inhibiting IL-33-mediated ILC2 activation and
      subsequent Th2 cytokine release via downregulation of the MyD88/NF-kappaB
      signaling pathway. (c)2018 ARSAAOA, LLC.

PMID- 30191680
TI  - Corneal tomographic features of postrefractive surgery ectasia.
AB  - The purpose of this study was to evaluate the tomographic features of
      postrefractive surgery eyes. This was a retrospective evaluation of clinical
      data. Three patients with post-LASIK (laser-assisted in situ keratomileusis) and
      two patients with post-SMILE (small incision lenticule extraction) ectasia were
      imaged with Scheimpflug imaging (SI, Pentacam) and optical coherence tomography
      (OCT, RTVue). Curvature and wavefront aberrations of the air-epithelium interface
      (A-E) and epithelium-Bowman's layer interface (E-B) were derived. OCT of normal
      and keratoconic eyes from an earlier study were compared with the data of the
      ectasia eyes. Curvature and aberrometry of the A-E interfaces were statistically
      similar between SI and OCT. However, OCT revealed a steeper and more aberrated E
      B interface than A-E though correlation between them was inferior to the
      correlation for keratoconic eyes. Furthermore, the magnitude of differences
      between the A-E and E-B interfaces was greater in the ectasia eyes than the
      keratoconic eyes. OCT could possibly assist better in selecting appropriate
      treatment plan for postrefractive surgery ectasia eyes than conventional
      tomographers.

PMID- 30191682
TI  - Mechanistic Study of the Synergy between Iron and Transition Metals for the
      Catalysis of the Oxygen Evolution Reaction.
AB  - A comprehensive study of the synergy between Fe and six transition metals (M=Ti,
      Co, Ni, Cu, Ag, Au), and how their M-Fe oxides electrocatalyze the oxygen
      evolution reaction (OER) was undertaken. Measurements were made using metal disks
      as the working electrodes and the addition of Fe3+ ions to the 1 m KOH
      electrolyte. The surfaces of the metal disks were oxidized after the OER.
      Interestingly, Fe interacted synergistically with all metal oxide layers except
      for that of Ti, resulting in enhanced catalytic activity for the OER. At an
      overpotential (eta) of 400 mV, the current densities of the Ni and Ag disks in
      the Fe3+ ions-spiked electrolyte increased by 253 and 132 times, respectively,
      whereas it was only 20-30 times for the Co and Cu disks (compared with the OER in
      pure KOH at eta=400 mV). The Tafel slopes of the Fe, Co, Ni, Cu, and Ag disks in
      1 m KOH+Fe3+ electrolyte were in the range of 29-42 mV dec-1 . The surface
      morphology and post-OER concentration of Fe in the catalysts could not be used to
      account for differences in the OER activities. Cyclic voltammetry showed that
      improvements in the OER performance were accompanied by changes in the redox
      features of the metal disk electrodes, which indicated the presence of electronic
      interactions between them and the Fe3+ . Strikingly, this was not observed
      between Ti and the Fe3+ ions, which could explain the lack of synergy between Ti
      and Fe3+ towards the OER catalysis. Electrochemical impedance spectroscopy
      indicated that the charge-transfer resistances of all the electrodes (except Ti)
      decreased after the addition of Fe3+ ions. Fe plays an important role in all
      these observed phenomena and we propose that the surface-adsorbed Fe species
      serve as the main active sites for OER in these synergistic M-Fe combinations.

PMID- 30191683
TI  - Cancer immunophenotyping by seven-colour multispectral imaging without tyramide
      signal amplification.
AB  - Checkpoint blockade immunotherapies have revolutionised cancer treatment in the
      last decade. Nevertheless, these are only beneficial for a small proportion of
      cancer patients. Important prognosticators for response to immunotherapy are the
      mutation burden of tumours as well as the quality and quantity of tumour
      infiltrating immune cells. High-throughput multiplex immunophenotyping
      technologies have a central role in deciphering the complexity of anti-tumour
      immune responses. Current techniques for the immunophenotyping of solid tumours
      are held back by the lack of spatial context, limitations in the number of
      targets that can be visualised simultaneously, and/or cumbersome protocols. We
      developed a tyramide signal amplification-free method for the simultaneous
      detection of seven cellular targets by immunofluorescence. This method overcomes
      limitations posed by most widespread techniques and provides a unique tool for
      extensive phenotyping by multispectral fluorescence microscopy. Furthermore, it
      can be easily implemented as a high-throughput technology for validation of
      discovery sets generated by RNA sequencing or mass cytometry and may serve in the
      future as a complementary diagnostic tool.

PMID- 30191684
TI  - Superparamagnetic graphene quantum dot as a dual-modality contrast agent for
      confocal fluorescence microscopy and magnetomotive optical coherence tomography.
AB  - A magnetic graphene quantum dot (MGQD) nanoparticle, synthesized by
      hydrothermally reducing and cutting graphene oxide-iron oxide sheet, was
      demonstrated to possess the capabilities of simultaneous confocal fluorescence
      and magnetomotive optical coherence tomography (MMOCT) imaging. This MGQD shows
      low toxicity, significant tunable blue fluorescence and superparamagnetism, which
      can thus be used as a dual-modality contrast agent for confocal fluorescence
      microscopy (CFM) and MMOCT. The feasibility of applying MGQD as a tracer of cells
      is shown by imaging and visualizing MGQD labeled cells using CFM and our in-house
      MMOCT. Since MMOCT and CFM can offer anatomical structure and intracellular
      details, respectively, the MGQD for cell tracking could provide a more
      comprehensive diagnosis.

PMID- 30191685
TI  - Polarization-resolved second-harmonic-generation imaging of dermal collagen fiber
      in prewrinkled and wrinkled skins of ultraviolet-B-exposed mouse.
AB  - Skin wrinkling is a typical symptom of cutaneous photoaging; however, the skin
      wrinkling depends on not only the actual age but also exposure history to
      ultraviolet B (UVB) rays in individuals. Therefore, there is considerable need
      for its assessment technique in vivo in skin cosmetics and antiaging dermatology.
      Wrinkles always appear as linear grooves in the skin, and dermal collagen fibers
      play an important role to determine the morphology and mechanical properties of
      the skin. Therefore, an optical probe sensitive to dermal collagen fiber and its
      orientation will be useful. Polarization-resolved second-harmonic-generation
      (SHG) microscopy is a promising approach for in vivo evaluation of collagen fiber
      orientation because the efficiency of SHG light is sensitive to collagen fiber
      orientation when the incident light is linearly polarized. We investigate
      orientation change of dermal collagen fiber in prewrinkled and wrinkled skins of
      the UVB-exposed mouse model using polarization-resolved SHG microscopy. A
      polarization anisotropic image of the SHG light indicates that the change of
      collagen fiber orientation starts in the prewrinkled skin of UVB-exposed mice,
      then the wrinkle appears. Furthermore, the dominant direction of collagen fiber
      orientation in the prewrinkled skin is significantly parallel to the wrinkle
      direction in the wrinkled skin. This result implies that the change of collagen
      fiber orientation is a trigger of wrinkling in cutaneous photoaging.

PMID- 30191686
TI  - Exploring the characteristics of effective communicators in healthcare.
AB  - Nurses require effective communication and interpersonal skills to provide
      optimal care, and to ensure that patients and their families and carers have a
      positive experience of receiving care. The new Nursing and Midwifery Council
      standards of proficiency for registered nurses, and for nurse education and
      training, published in May 2018, recognise that future nurses will be practising
      in increasingly complex roles and environments. This article identifies the
      essential communication skills that will be required by nurses in the future,
      summarising the characteristics of a modern nurse communicator. It also suggests
      various approaches that nurses can use to develop their communication skills.

PMID- 30191687
TI  - Combined antegrade-retrograde approach to facilitate the endovascular stent-graft
      repair of a ruptured superficial femoral artery pseudoaneurysm.

PMID- 30191681
TI  - Evidence for PTGER4, PSCA, and MBOAT7 as risk genes for gastric cancer on the
      genome and transcriptome level.
AB  - Genetic associations between variants on chromosome 5p13 and 8q24 and gastric
      cancer (GC) have been previously reported in the Asian population. We aimed to
      replicate these findings and to characterize the associations at the genome and
      transcriptome level. We performed a fine-mapping association study in 1926 GC
      patients and 2012 controls of European descent using high dense SNP marker sets
      on both chromosomal regions. Next, we performed expression quantitative trait
      locus (eQTL) analyses using gastric transcriptome data from 143 individuals
      focusing on the GC associated variants. On chromosome 5p13 the strongest
      association was observed at rs6872282 (P = 2.53 * 10-04 ) and on chromosome 8q24
      at rs2585176 (P = 1.09 * 10-09 ). On chromosome 5p13 we found cis-eQTL effects
      with an upregulation of PTGER4 expression in GC risk allele carrier (P = 9.27 *
      10-11 ). On chromosome 8q24 we observed cis-eQTL effects with an upregulation of
      PSCA expression in GC risk allele carrier (P = 2.17 * 10-47 ). In addition, we
      found trans-eQTL effects for the same variants on 8q24 with a downregulation of
      MBOAT7 expression in GC risk allele carrier (P = 3.11 * 10-09 ). In summary, we
      confirmed and refined the previously reported GC associations at both chromosomal
      regions. Our data point to shared etiological factors between Asians and
      Europeans. Furthermore, our data imply an upregulated expression of PTGER4 and
      PSCA as well as a downregulated expression of MBOAT7 in gastric tissue as risk
      conferring GC pathomechanisms.

PMID- 30191688
TI  - CHARACTERISTIC OF THE CHROMATIN TYPE CORRESPONDING TO THIN "GREY" BANDS IN
      POLYTHENE CHROMOSOMES OF DROSOPHILA MELANOGASTER.
AB  - Recently, we developed a bioinformatic algorithm dividing drosophila genome into
      4 types of chromatin which differ in protein composition. This allows us to
      propose a model of structural and functional organization of interphase
      chromosomes which postulates an existence of correlation between the chromatin
      types and morphological structures of polytene chromosomes. So, constantly and
      everywhere open chromatin type named "aquamarine" is characteristic of
      interbands, while the combinations of the other three types ("lazurite",
      "malachite" and "ruby") form the bands. In this study, we characterized protein
      composition, genetic organization and morphological features of 39 "lazurite"
      chromatin regions in polytene chromosomes. We found out that "lazurite"-chromatin
      usually form thin "grey" bands and more rarely - boundary portions of large
      bands. This type of chromatin contains coding parts and 3R-ends of genes and is
      enriched with proteins and histone modifications associated with active
      transcription at the stage of elongation. The expression patterns of these genes
      differ greatly depending on the type of chromatin in their 5R-regions.

PMID- 30191689
TI  - A COMBINED METHOD FOR MAPPING POLYTHENE CHROMOSOMES ON THE EXAMPLE OF THE FOURTH
      MICROCHROMOSOME OF DROSOPHILA MELANOGASTER.
AB  - Genetic activity of interphase chromosomes is associated with their structural
      organization, but the mechanism of these relations is still unclear. Classic
      polythene chromosomes of dipteran insects are a convenient model for such
      investigations. Despite intensive study of polythene chromosomes of Drosophila
      melanogaster is carried out, an exact conformity of bands and interbands to the
      molecular map of the genome remains unknown in most cases. For addressing this
      issue, the genetic map and molecular characteristics of chromatin have been
      compared with the banding pattern of the fourth chromosome, which is the smallest
      chromosome in the D. melanogaster genome and is different in many ways from other
      chromosomes. This is a unique chromatin domain of D. melanogaster, which is
      characterized by specific proteins, including HP1, POF and EGG. Matching of
      cytological and physical maps of the fourth chromosome has been carried out by
      FISH. Genomic coordinates of bands and interbands have been determined. This
      result makes it possible to investigate the regulation of gene activity of the
      fourth chromosome in the context of molecular characteristics of cytological
      structures in which these genes are located.

PMID- 30191690
TI  - LOCALIZATION OF MOBILE P-ELEMENT INSERTIONS IN DOMAINS OF ACTIVE AND REPRESSED
      CHROMATIN IN DROSOPHILA MELANOGASTER'S GENOME.
AB  - Classic polythene chromosomes from dipteran insects are extensively used as a
      model for interphase chromosomes. The peculiar morphology of polythene
      chromosomes is formed by the alternating densely packed chromatin of bands and
      less compact interbands. In recent years numerous data have been obtained on the
      precise localization of different proteins on the molecular map in the interphase
      chromosomes. A special algorithm has been developed based on the interband
      specific protein composition. This algorithm allows us to detect the positions of
      bands and interbands in the whole Drosophila's genome. The goal of our
      investigation is to analyse of P-elements distribution in localized bands and
      interbands. We have found that P-elements distribution is not random in
      Drosophila's genome. Insertions of P-elements predominantly take place in regions
      of genome predicted by algorithm as interbands. The density of P-element
      insertions in compacted bands is notably lower.

PMID- 30191691
TI  - COMPREHENSIVE APPROACH TO MAPPING LATE-REPLICATING BANDS IN POLYTHENE CHROMOSOMES
      OF DROSOPHILA MELANOGASTER.
AB  - Heterogeneity of chromatin structure underlies the banding pattern of Drosophila
      polythene chromosomes. Recently, a four-color model of chromatin has been
      proposed, with one chromatin type, aquamarine, largely corresponding to
      interbands (Zhimulev et al., 2014). In this model, most of the previously mapped
      regions of intercalary heterochromatin are represented by the ruby chromatin
      type. In the present report, we used the distal part of the chromosome arm 2R to
      show that all dense late-replicating bands in this region invariably encompass
      ruby chromatin type. We propose a comprehensive approach that combines cytology
      mapping data of the FlyBase-annotated genes, novel tools for predicting
      cytogenetic features of chromosomes based on their prothein composition and data
      on the sequence of replication in polythene chromosome bands. This approach
      allows to establish accurately the correspondence between reference late
      replicating bands visible on cytology maps and the molecular map.

PMID- 30191692
TI  - PECULIARITIES OF THE STRUCTURE AND EXPRESSION OF HUMAN SPHINGOMYELIN SYNTHASE 1
      GENE (SGMS1).
AB  - The article is a review of the results of the study of the structural and
      functional organization of the human sphingomyelin synthase 1 gene (SGMS1) in
      Human Molecular Genetics Department of Institute of Molecular Genetics RAS. SGMS1
      gene encodes an essential enzyme which is involved in the synthesis of
      sphingomyelin and diacylglycerol from phosphatidylcholine and ceramide, wich
      determines its participation in the regulation of intracellular vesicular
      transport, cholesterol metabolism, cell proliferation, apoptosis and other
      significant processes. Our research has shown that the SGMS1 gene is located on
      the chromosome 10, has a size of 320 kb and contains more than 20 exons. A
      detailed study of the SGMS1 gene's structure allowed us to identify the variety
      of its transcripts. mRNA isoforms with different fragments of 5R untranslated
      region (5R UTR) and encoding the full length protein, as well as transcripts
      resulting from alternative combinations of exons and containing the coding region
      of the gene and 3R UTR have been discovered. We have found new transcripts among
      the products of SGMS1 gene - circular RNAs, which mostly contained sequences of
      multi-exon 5R UTR of the gene. They are conservative and predominantly expressed
      in the brain. Circular RNAs of SGMS1 gene had a large number of binding sites for
      a microRNA that may determine the functional significance of these molecules. The
      review describes the latest information about the structural and functional
      organization of the human gene SGMS1 as well as the features of its expression.

PMID- 30191693
TI  - THE FUNCTIONAL ROLE OF SMALL HEAT SHOCK PROTEIN Hsp67Bc IN DROSOPHILA
      MELANOGASTER.
AB  - Heat shock proteins are universal agents protecting all known organisms from
      environmental stresses. These proteins are classified into six families differing
      in their structure and function, yet having a common purpose of maintaining
      cellular proteins in operating condition. The small heat shock protein family has
      the most diversified set of effects on the organism's vital activity with a great
      number of its members' features studied thoroughly in a fruit fly Drosophila
      melanogaster, which is regarded as a convenient model object. In this review, we
      represent and discuss data on the role of Drosophila melanogaster Hsp67Bc
      protein, which was earlier identified as the closest functional ortholog of human
      HSPB8 small heat shock protein.

PMID- 30191694
TI  - LAMPBRUSH CHROMOSOMES AS A MODEL FOR EXPLORATION INTO LOCI OF NUCLEAR DOMAINS
      FORMATION.
AB  - Nuclear domains can be divided into two major groups: those arising freely in
      nucleoplasm and those forming at specific chromosomal loci as a result of their
      activity. The advantages of giant transcriptionally active lampbrush chromosomes
      for the investigation of nuclear bodies formed in particular chromosomal regions
      have been demonstrated in a series of studies. We propose to use two strategies
      to analyze the loci of nuclear domains formation on lampbrush chromosomes typical
      for avian and amphibian oocytes. The first approach implies consecutive mapping
      of BAC-clones, containing the fragments of DNA assigned to genomic coordinates,
      in close proximity to the nuclear domains. The second approach is based on
      mechanical microdissection of chromosomal regions adjacent to a particular
      nuclear structure. DNA of dissected material can be amplified by PCR with
      degenerate primers and mapped by fluorescent in situ hybridization (FISH) on
      chromosomal spreads. Utilization of high-throughput sequencing (next generation
      sequencing, NGS) technologies also proves to be prospective for subsequent
      deciphering of regions underlying nuclear structures formation. Deciphered
      fragments can be aligned against reference genome assembly to define precisely
      the loci responsible for nuclear domains assembly. In this review, the
      possibilities of using two complementary strategies for investigation of nuclear
      domains associated with lampbrush chromosomes are demonstrated.

PMID- 30191695
TI  - THE INFLUENCE OF THE Chd1 CHROMATIN ASSEMBLY AND REMODELING FACTOR MUTATIONS ON
      DROSOPHILA POLYTHENE CHROMOSOME ORGANIZATION.
AB  - Chromatin assembly is a fundamental process that is essential for chromosome
      duplication subsequent to DNA replication. In addition, histone removal and
      incorporation take place constantly throughout the cell cycle in the course of
      DNA-utilizing processes, such as transcription, damage repair or recombination.
      In vitro chromatin assembly requires the concerned action of histone chaperones
      and ATP-utilizing chromatin assembly factors. ATP-dependent chromatin assembly
      and remodeling factor CHD1 (Chromo-ATPase/Helicase-DNA-binding protein 1) is
      involved in multiple cellular processes, such as the replication independent
      assembly of nucleosomes containing the variant histone H3.3, regulation of
      transcription initiation, elongation and termination; determination of steam cell
      pluripotency and in cancer development. We have shown that mutations in
      Drosophila Chd1 gene induce a decondensation of the male X chromosome, similar to
      that induced by mutations in the iswi nucleosome remodeling factor. An effect of
      Chd1 null mutation can be increased by deficiency of one of the genes, encoding
      variant histone H3.3, His 3.3 B, suggesting that the role of CHD1 in the control
      of male X chromosome organization can be mediated by CHD1 activity in H3.3
      histone deposition and exchange.

PMID- 30191696
TI  - THE COMPOSITION OF SWI/SNF CHROMATIN REMODELING COMPLEX IS STABLE DURING GENE
      TRANSCRIPTION.
AB  - SWI/SNF protein complex is a unique transcription activator, which takes part in
      almost all stages of transcription regulation including preinitiation complex
      formation, transition of RNA polymerase II to transcription elongation, enhancer
      and insulator action. Recently it was found that particular subunits of SWI/SNF
      become involved in gene transcription on distinct stages. In the current work we
      investigate subunit composition of complexes formed with Brahma protein (ATPase
      of SWI/SNF complex) on the sages of initiation and elongation of gene
      transcription. As the result we have demonstrated the composition stability of
      SWI/SNF complex during gene transcription. We suppose that differences in
      recruitment of particular SWI/SNF subunits, that were distinguished earlier, are
      due to formation of complexes distinct from SWI/SNF and not including Brahma
      ATPase. Functioning of non-enzymatic subunits independently of the main complex
      had not been shown earlier. This finding extend our knowledge concerning
      functional properties of the proteins, involved in chromatin remodeling process.

PMID- 30191697
TI  - PATHWAYS OF SPINDLE FORMATION IN DROSOPHILA MITOTIC AND MEIOTIC CELLS.
AB  - Spindle assembly relies on three main classes of microtubules (MTs): MTs
      nucleated by the centrosomes, MTs nucleated near the chromosomes/kinetochores and
      MTs nucleated from preexisting MTs through the augmin-based pathway. Here, we
      review the roles of these microtubule generation pathways in Drosophila spindle
      assembly. The extant results indicate that female meiotic cells, male meiotic
      cells, larval brain cells and S2 tissue culture cells exploit specific pathway
      combinations for generating the MTs necessary for spindle formation. Thus,
      different Drosophila cell types have specific modes of spindle assembly, which
      might be related to specific functional and developmental requirements.

PMID- 30191698
TI  - GENOTYPING AND COAT COLOUR DETECTION OF ANCIENT HORSES FROM BURYATIA.
AB  - From genetic point of view, differences between ancient and modern horses can be
      reconstructed by using the phylogeographic analysis of mitochondrial genomes and
      by studying phenotypically important nuclear loci. The variety of modern horse
      coat colors resulted from artificial selection indicates a high degree of
      domestication. We have conducted the phylogenetic analysis of mitochondrial DNA
      extracted from bone samples of six ancient horses from Tsaramburial in the
      Republic of Buryatia, and established that they belong to a haplogroup E by
      Achilli's classification. This haplogroup is found among modern horses of the
      Maremmano breed from Italy. Gray coat color different from wild type have been
      detected in two ancient horses, which demonstrates a sufficiently high
      domestication level of Buryat horses during the period I century BC to I century
      AD. The analysis of the mitochondrial genome hypervariable region fragments
      revealed that ancient Buryat horses belong to a haplotype X3 by Cieslak's
      classification, which is ancestral to the haplogroup X3 of modern horses in
      Mongolia, Tuva, and Buryatia.

PMID- 30191699
TI  - ROLE OF TELOMERIC PROTEIN COMPLEX AND TELOMERIC RNA IN EARLY DEVELOPMENT OF
      DROSOPHILA.
AB  - Investigation of the role of the telomeric complex during oogenesis and early
      development is important for understanding the mechanisms controlling the
      integrity of the genetic information. Using Drosophila, as a model, we examine
      the features of the telomeres in the female germ cells and early embryonic
      development. Similarities and differences between telomeric factors, forming a
      protective telomeric complex in somatic and germ tissues will be discussed in
      this review. Germline knockdown of telomeric proteins led to chromosome fusions
      and different mitotic chromosome defects in the early stages of embryogenesis. It
      was found that depletion of telomeric factors caused accumulation of abundant
      telomeric RNA that was localized near the centrosome, microtubule organizing
      center, during syncytial stage of early embryogenesis. We suggest that telomeric
      transcripts may play a role in the destruction of the mitotic apparatus upon
      telomere dysfunction condition. Our data allow us to take a new look at the
      possible functions of telomeric RNA.

PMID- 30191700
TI  - SYNAPTONEMAL COMPLEX CONFIGURATIONS IN ROBERTSONIAN HETEROZYGOTES.
AB  - We present here the classification of synaptonemal complex (SC) configurations in
      meiotic prophase I in animals heterozygous for Robertsonian (Rb) translocations
      on the basis of own studies and literature data. Configurations of SC
      multivalents, due to the homology of Rb metacentrics on one or both arms, as well
      as the ability of multivalents to form a temporary association, led to the
      formation of chromosome chains.

PMID- 30191701
TI  - SPATIAL ORGANIZATION OF CHROMOSOMES IN MALARIA MOSQUITOES.
AB  - Malaria mosquitoes are vectors of dangerous human diseases and a model system for
      investigations of chromosome evolution, heterochromatin organization, and nuclei
      architecture in the cells of the reproductive system. Investigations of nurse
      cells chromosomes are aimed at understanding of mechanisms that cause
      interspecies differences in the nuclear spatial organization in these cells. One
      of the most important tasks of this research is the undestanding of molecular
      organization of the chromosome regions that are attached to the nuclear envelope.
      In the present review, the recent achievements in this field of research are
      described and unsolved problems of the spatial chromosome organization are
      identified.

PMID- 30191702
TI  - VARIABILITY OF CENTROMERIC HISTONE H3 VARIANTS AND PHYLOGENETIC RELATIONSHIPS IN
      SECALE.
AB  - We examined nucleotide sequence variation in centromeric histone H3 (CENH3) in
      fifteen rye species and subspecies, including annuals, perennials, self
      pollinating and cross-pollinated plants. Levels of genetic variation within N
      terminal tail (NTT) and histone fold domain (HFD) were estimated as average per
      site pairwise nucleotide diversity (p) and as the number of segregating
      polymorphic sites (S). A comparison of nucleotide diversity (ptot) for NTT and
      HFD showed that estimates of diversity are consistently greater in NTT. Our
      estimates of NTT nucleotide diversity for perennial Secale strictum C. Presl were
      similar to those observed in annual S. cereale L., elevating those estimates for
      ancient species S. silvestre. A similar pattern of nucleotide polymorthism was
      observed between the self-pollinating and cross-pollinated subspecies. These
      results suggest that lower nucleotide diversity within CENH3 for some wild and
      cultivated subspecies of Secale may be attributable to narrow ecological niche,
      either evolutionary age or breeding.

PMID- 30191703
TI  - CHARACTERIZATION OF CENTROMERIC HISTONE H3 VARIANTS IN ALLOPOLYPLOIDS OF WHEAT
      AND RYE.
AB  - Chromosome elimination of one parental species in hybrid cell observed even after
      successful fertilization is one of a common phenomenon and the main problems of
      remote hybridization. Centromeres regulate the process of faithful segregation of
      chromosomes during cell division. Constant component of the centromeric chromatin
      is a specialized histone H3 modification (CENH3). CENH3 consists of a conserved C
      terminal domain (HFD) and a more variable N-terminal tail (NTT), which plays an
      important role for CENH3 loading in centromeric chromatin during cell division.
      In the present study, we performed comparative analysis of CENH3 variants
      expression in allopolyploids, as well as in different parental varieties of rye
      (Secale cereale L.) and wheat (Triticum aestivum L.). The varieties of both
      genera were used as maternal plants. In the coding sequences of the NTT CENH3 we
      identified the full-length copies of 216 bp with characteristic single nucleotide
      polymorphisms (SNPs), and copies with 21 bp or 66 bp deletions. The wheat and rye
      NTT CENH3 copies with 21 bp deletion have not differences in the nucleotide
      sequences, the rye copies with 66 bp deletion reveal two specific SNPs, which
      were also found in plant of wheat-rye allopolyploids having 57 chromosomes. The
      full-length sequences of rye NTT CENH3 show specific SNPs, which were also
      detected in the full-length sequences of all analyzed plants of wheat-rye
      allopolyploids. These results indicate that expression of CENH3 copies belonging
      to each parent was observed in hybrid genomes of aneuploids which arose from
      octoploid triticale. The NTT CENH3 copies with deletions were not found in
      secalotriticum (Secalotriticum). The full-length sequences show two rye specific
      SNPs. Their frequency in secalotriticum significantly exceeds that in hexaploid
      triticale Mikhas. This fact points to the preferential synthesis of the full NTT
      CENH3 copies of the rye parental variety in the secalotriticum genome.

PMID- 30191704
TI  - FACTORS GOVERNING THE PATTERN OF SPINDLE MICROTUBULE REGROWTH AFTER TUBULIN
      DEPOLYMERIZATION.
AB  - We analyzed the pattern of spindle microtubule (MT) regrowth after cold- or
      colcemid-induced MT depolymerization in Drosophila S2 cells. Cold-induced MT
      disassembly at low temperature (-2  degrees C) destroyed kinetochore-driven MT
      regrowth without affecting astral MT formation. Conversely, colcemid-induced MT
      depolymerization strongly impaired centrosome-dependent MT nucleation, allowing
      kinetochore-driven MT regrowth. Collectively, these results indicate that the
      kinetochore- and the centrosome-mediated MT assembly pathways exploit molecular
      mechanisms that are at least in part different.

PMID- 30191705
TI  - Highly Surface-Embossed Polydimethylsiloxane-Based Triboelectric Nanogenerators
      with Hierarchically Nanostructured Conductive Ni-Cu Fabrics.
AB  - Wearable fabric-based energy harvesters have continued to gain importance for use
      in portable consumer electronics as an ecofriendly energy source that is
      independently self-powered by various activities. Herein, we address the output
      features of highly flexible Ni-Cu fabric-based triboelectric nanogenerators (F
      TENG) employing surface-embossed polydimethylsiloxane (SE-PDMS) layers, as a
      crucial approach for enhancing power generation. Such SE-PDMS configurations were
      achieved via control of the ZnO nanowire (NW) and nanoflake (NF) frames initially
      prepared on bare Ni-Cu fabrics by a hydrothermal approach. The wearable SE-PDMS
      and Al-evaporated fabrics, respectively, served as triboelectric bottom and top
      materials in F-TENGs. Along with the structural analyses of the F-TENGs, the
      enhanced power generation of the F-TENGs was illustrated via the application of
      periodic mechanical stress using an adjustable bending machine. The present
      approach may provide a useful and simple route for developing self-powered,
      wearable, and smart electronics based on fabric substrates.

PMID- 30191706
TI  - Black GaAs by Metal-Assisted Chemical Etching.
AB  - Large area surface microstructuring is commonly employed to suppress light
      reflection and enhance light absorption in silicon photovoltaic devices,
      photodetectors, and image sensors. To date, however, there are no simple means to
      control the surface roughness of III-V semiconductors by chemical processes
      similar to the metal-assisted chemical etching of black Si. Here, we demonstrate
      the anisotropic metal-assisted chemical etching of GaAs wafers exploiting the
      lower etching rate of the monoatomic Ga<111> and <311> planes. By studying the
      dependence of this process on different crystal orientations, we propose a
      qualitative reaction mechanism responsible for the self-limiting anisotropic
      etching and show that the reflectance of the roughened surface of black GaAs
      reduces up to ~50 times compared to polished wafers, nearly doubling its
      absorption. This method provides a new, simple, and scalable way to enhance light
      absorption and power conversion efficiency of GaAs solar cells and
      photodetectors.

PMID- 30191707
TI  - Flexible Porous Polydimethylsiloxane/Lead Zirconate Titanate-Based Nanogenerator
      Enabled by the Dual Effect of Ferroelectricity and Piezoelectricity.
AB  - Flexible piezoelectric nanogenerators have drawn considerable attention for their
      wide applications in harvesting ambient mechanical energy. Here, we report a
      flexible porous nanogenerator (FPNG) based on the dual effect of ferroelectricity
      and piezoelectricity. The electric output originated from the combination of the
      above two effects can be constructively added up, resulting in an enhancement of
      the electric output. With dimensions of 2 * 2 * 0.3 cm3, the FPNG can generate an
      open-circuit voltage ( Voc) of 29 V and a short-circuit current ( Isc) of 116 nA
      under a compressive force of 30 N. Besides, the FPNG is applicable to other forms
      of mechanical stimuli, including twisting and bending. Harvesting energy from a
      rowing bicycle tire is demonstrated in this report. This work provides a new
      route to promoting the electric output of piezoelectric nanogenerators.

PMID- 30191708
TI  - Thermal and Plasmonic Stabilization of Silver Nanostructures Using a Bilayer
      Anchoring Technique.
AB  - In this work, we demonstrate how to suppress the shape instability of silver (Ag)
      nanotriangular pyramids following high-temperature annealing without a coating or
      encapsulation, thus producing a more stable optical plasmonic system. Nanosphere
      lithography (NSL) was used to fabricate large-area arrays of nanotriangular
      pyramids of Ag on glass substrates. By using a combination of morphology and
      spectroscopic studies it was found that exposure of this system to high
      temperatures of 473 K and beyond in air led to a rapid change in nanostructure
      shape, and thus, the surface area, with a substantial change to the original
      plasmonic character. On the other hand, NSL nanotriangular pyramids made from
      bilayers of Ag on Co or Co on Ag showed much smaller changes in shape and area
      following annealing up to 573 K in air. In the case of pure Ag, the NSL
      nanotriangular pyramid changed into a more spherical shape with an overall
      decrease of ~24% in its surface area following annealing at 573 K. This lead to a
      large blue shift of over ~287 nm or ~39% in the location of the dipolar plasmonic
      resonance. On the other hand, the triangular shape of Ag was retained in both the
      metal bilayer cases, with much smaller area changes of ~10 and ~9%, for the Ag
      deposit when on Co and when under Co, respectively. Consequently, the plasmonic
      shifts were substantially smaller, of ~65 nm or about 9%, in these bilayer
      systems. The mechanism for this stabilization was attributed to the higher
      surface energy of Co and much lower diffusivity of Co as well as Ag on Co that
      resulted in an anchoring of the Ag shape to its original state. The plasmonic
      quality factor for the bimetal NSL nanotriangular pyramids also showed
      substantially improved stability over pure Ag, further indicating that this
      anchoring approach is a viable pathway to produce pristine Ag surfaces for high
      temperature plasmonic applications.

PMID- 30191709
TI  - High-Performance InSe Transistors with Ohmic Contact Enabled by Nonrectifying
      Barrier-Type Indium Electrodes.
AB  - The electrical contact to two-dimensional (2D) semiconductor materials is
      decisive to the electronic performance of 2D semiconductor field-effect devices
      (FEDs). The presence of a Schottky barrier often leads to a large contact
      resistance, which seriously limits the channel conductance and carrier mobility
      measured in a two-terminal geometry. In contrast, Ohmic contact is desirable and
      can be achieved by the presence of a nonrectifying or tunneling barrier. Here, we
      demonstrate that a nonrectifying barrier can be realized by contacting indium
      (In), a low work function metal, with layered InSe because of a favorable band
      alignment at the In-InSe interface. The nonrectifying barrier is manifested by
      Ohmic contact behavior at T = 2 K and a low barrier height, PhiB = 50 meV. This
      Ohmic contact enables demonstration of an on-current as large as 410 MUA/MUm,
      which is among the highest values achieved in FEDs based on layered
      semiconductors. A high electron mobility of 3700 and 1000 cm2/V.s is achieved
      with the two-terminal In-InSe FEDs at T = 2 K and room temperature, respectively,
      which can be attributed to enhanced quality of both conduction channel and the
      contacts. The improvement in the contact quality is further proven by an X-ray
      photoelectron spectroscopy study, which suggests that a reduction effect occurs
      at the In-InSe interface. The demonstration of high-performance In-InSe FEDs
      indicates a viable interface engineering method for next-generation, 2D
      semiconductor-based electronics.

PMID- 30191710
TI  - Detection of Enzymes, Viruses, and Bacteria Using Glucose Meters.
AB  - We have developed innovative assays that can detect enzymes rapidly. Paracetamol-
      or catechol-bearing compounds, when exposed to their respective enzymes, released
      paracetamol or catechol, which can be detected using a standard glucose meter.
      This approach was used to detect a number of diverse analytes that include
      enzymes such as beta-galactosidase and alpha-mannosidase and pathogens such as
      influenza viruses, Streptococcus pneumoniae, and E. coli rapidly. The limit of
      detection for all analytes was extremely low and clinically relevant for
      influenza viruses. We also demonstrate that glucose oxidase or glucose
      dehydrogenase is not required because the paracetamol gets oxidized directly on
      the electrode surface. This indicates that test strips without glucose oxidase or
      dehydrogenase can be used, and we can detect analytes in the presence of high
      levels of background glucose. We demonstrate this unique nature of the assay to
      detect paracetamol in simulated urine and sheep blood without background
      interference of intrinsic glucose, indicating that glucose meters can be used to
      detect nonglucose analytes without background glucose interference.

PMID- 30191711
TI  - In Situ Imaging of Furin Activity with a Highly Stable Probe by Releasing of
      Precipitating Fluorochrome.
AB  - Furin, a kind of trans-Golgi proprotein convertases, plays important role in
      various physiological processes. It is overexpressed in many cancers and relates
      to tumor growth and migration. In situ detection and imaging of furin is of great
      significance for obtaining real-time information about its activity. However, the
      previously reported fluorescent probes for furin usually failed to realize in
      situ detection and long-term bioimaging, because these probes are based on water
      soluble fluorophores, which tend to diffuse away from the reaction sites after
      converted by furin. Such a problem can be addressed by designing a probe, which
      releases a precipitating fluorophore upon furin conversion. Herein, we developed
      a probe HPQF for in situ detection of endogenous furin activity and long-term
      bioimaging by integrating a strictly insoluble solid-state fluorophore 6-chloro-2
      (2-hydroxyphenyl) quinazolin-4(3H)-one (Cl-HPQ) with a furin specific peptide
      substrate (RVRR) through a self-immolative linker. The HPQF probe shows high
      selectivity and sensitivity to furin. Upon converted by furin, HPQF releases free
      Cl-HPQ, which precipitates near the enzyme active site. The precipitates emit
      bright solid-state fluorescence for in situ imaging. HPQF could truly visualize
      the location of intracellular furin, which was further confirmed by
      colocalization and immunofluorescence experiments. Excitingly, the long-term
      bioimaging was also achieved benefiting from its outstanding signal-stability and
      antidiffusion ability. HPQF was further utilized to monitor the level change of
      furin under stabilizing of hypoxia-inducible factor (HIF) regulated by cobalt
      chloride (CoCl2) as well as visualization of furin in MDA-MB-468 cell tumor
      tissues.

PMID- 30191712
TI  - Chemistry and Properties of Indolocarbazoles.
AB  - The indolocarbazoles are an important class of nitrogen heterocycles which has
      evolved significantly in recent years, with numerous studies focusing on their
      diverse biological effects, or targeting new materials with potential
      applications in organic electronics. This review aims at providing a broad survey
      of the chemistry and properties of indolocarbazoles from an interdisciplinary
      point of view, with particular emphasis on practical synthetic aspects, as well
      as certain topics which have not been previously accounted for in detail, such as
      the occurrence, formation, biological activities, and metabolism of indolo[3,2-
      b]carbazoles. The literature of the past decade forms the basis of the text,
      which is further supplemented with older key references.

PMID- 30191713
TI  - Water-Stable Metal-Organic Framework for Effective and Selective Cr2O72- Capture
      through Single-Crystal to Single-Crystal Anion Exchange.
AB  - Effective and selective capture of environmentally toxic Cr2O72- from water is
      desirable for both environment protection and human health, but it still remains
      a significant challenge. We present a water-stable cationic metal-organic
      framework (MOF) with large nanotubular channels ( ca. 1.4 * 1.4 nm2), (1-Cl).
      Remarkably, the resulting porous material exhibits rapid aqueous-phase removal of
      Cr2O72- via an anion-exchange manner. Meaningfully, the capture and separation of
      aqueous Cr2O72- are highly selective even in the presence of other disturbing
      anions. More importantly, the crystal structure of 1-Cl after anion exchange (1
      Cr2O7) could be determined by single crystal X-ray diffraction, elaborating the
      single-crystal-to-single-crystal (SC-SC) transformation. The Cr2O72- removal
      process by 1-Cl thus was directly uncovered by the crystal structure of Cr2O72-
      incorporated 1-Cr2O7.

PMID- 30191714
TI  - Exploring the Uncharacterized Human Proteome Using neXtProt.
AB  - 20,230 protein-coding genes have been predicted from the analysis of the human
      genome (neXtProt release 2018-01-17), and about 10% of them are still lacking
      functional annotation, either predicted by bioinformatics tools or captured from
      experimental reports. A systematic exploration of the available literature on
      uncharacterized human genes/proteins led to proposal of functional annotations
      for 113 proteins and to consolidation of a list of 1,862 uncharacterized human
      proteins. The advanced search functionality of neXtProt was used extensively in
      order to examine the landscape of the uncharacterized human proteome in terms of
      subcellular locations, protein-protein interactions, tissue expression,
      association with diseases, and 3D structure. Finally, a deep data mining in
      various publicly available resources allowed building functional hypotheses for
      26 uncharacterized human proteins validated at protein level (uPE1). These
      hypotheses cover the fields of cilia biology, male reproduction, metabolism,
      nervous system, immunity, inflammation, RNA metabolism, and chromatin biology.
      They will require experimental validation before they can be considered for
      annotation. Despite technological progresses, the pace of human protein
      characterization studies is still slow. It could be accelerated by a better
      integration of existing knowledge resources and by initiating large collaborative
      projects involving specialists of different biology fields. We hope that our
      analysis will contribute to set up the ground for such collaborative approaches
      and will be exploited by the HUPO Human Proteome Project teams committed to
      characterize uPE1 proteins.

PMID- 30191715
TI  - Organocatalytic Aza-Friedel-Crafts/Lactonization Domino Reaction of Naphthols and
      Phenols with 2-Acetamidoacrylate to Naphtho- and Benzofuranones Bearing a
      Quaternary Center at the C3 Position.
AB  - N-Acetyl ketimine generated from methyl 2-acetamidoacrylate was explored to
      develop an unprecedented domino aza-Friedel-Crafts/lactonization reaction with
      naphthols and phenols (including 5-hydroxyindoles). This novel method requires a
      catalyst loading of only 5 mol % of a phosphoric acid catalyst and provides a new
      series of 3-NHAc-naphtho- and benzofuranone derivatives bearing tetra-substituted
      stereogenic centers in moderate-to-good yields. The enantioselective variant
      using BINOL-derived phosphoric acids was also explored with 1-naphthol, providing
      the desired product with moderate enantioselectivities (up to 99:1 following
      recrystallization).

PMID- 30191716
TI  - Diastereoselective Synthesis of Unnatural Amino Acids by Alkylation of alpha-
      tert-Butanesulfinamide Auxiliary-Bound Enolates.
AB  - A new chiral auxiliary for the diastereoselective alkylation of amino ester
      enolates that takes advantage of chiral information stored on the enolate side of
      the amino ester substrate has been developed. Chiral alpha-sulfinamido esters
      were alkylated under basic conditions in good yields (up to 90%) and good to high
      diastereoselectivities (generally >6:1) to provide unnatural mono- and
      alpha,alpha-disubstituted amino acid derivatives. This auxiliary allowed for the
      ready conversion of ester functionality without the need for esoteric reagents.
      Furthermore, the auxiliary is easily removed to provide enantiopure amino acids.
      Computational studies revealed that a chelated transition state governs
      electrophile addition from the convex face of a transient bicyclic intermediate.
      This method allows ready access to enantioenriched natural and unnatural amino
      acids.

PMID- 30191717
TI  - Synthesis of Heteroleptic Phosphorus(I) Cations by P+ Transfer.
AB  - Reported are general synthetic approaches for the syntheses of asymmetrically
      substituted phosphorus(I) cations by P+ transfer from [dppeP]+ (dppe = 1,2
      bis(diphenylphosphino)ethane). The first method grants access to acyclic
      derivatives and is accomplished by the sequential substitution of dppe using
      first a sterically encumbered ligand which cannot form a stable homoleptic
      complex, followed by a second equivalent of a less sterically demanding ligand.
      The second method grants access to cyclic derivatives and utilizes asymmetric
      hybrid phosphine/N-heterocyclic carbene ligands. Interplay between the different
      ligand types and their stoichiometries relative to those of [dppeP]+ also allows
      for the isolation of symmetrical derivatives with pendant phosphines.

PMID- 30191718
TI  - Hydrogels Incorporating Au@Polydopamine Nanoparticles: Robust Performance for
      Optical Sensing.
AB  - Stimuli-responsive hydrogels (SRhG) that undergo response to physicochemical
      stimuli have been broadly applied in separation, biosensing, and drug delivery.
      Since, most of the SRhG are based on the structural behaviors (swelling or
      collapse). Herein, we describe a more simple and convenient colorimetric SRhG of
      polydopamine-coated gold nanoparticles (Au@PDA NPs) hydrogel. The newly developed
      SRhG is based on the in situ surface chemistry of Au@PDA NPs with core-shell
      structure embedding in agarose hydrogel. Silver ions can in situ form Ag NPs on
      surfaces of Au@PDA NPs (Ag_Au@PDA NPs with core-satellites like structure) at
      ambient conditions, which shift the localized surface plasmon resonance (LSPR)
      absorption peak and result in color change. The solid sensing phase of SRhG shows
      greatly improved stability and anti-interference ability comparing to that of
      solution phase sensing. With rational designs, Au@PDA NPs hydrogel shows great
      potential in optical sensing, for example, biothiol detection, and coupled with
      enzyme-cascade reaction for acetylcholinesterase activity detection and inhibitor
      assays with excellent sensitivity and selectivity.

PMID- 30191720
TI  - Making delusions of infestation understandable: A worthy goal?

PMID- 30191719
TI  - Peroxiredoxin5 Controls Vertebrate Ciliogenesis by Modulating Mitochondrial
      Reactive Oxygen Species.
AB  - AIMS: Peroxiredoxin5 (Prdx5), a thioredoxin peroxidase, is an antioxidant enzyme
      that is widely studied for its antioxidant properties and protective roles in
      neurological and cardiovascular disorders. This study is aimed at investigating
      the functional significance of Prdx5 in mitochondria and at analyzing its roles
      in ciliogenesis during the process of vertebrate development. RESULTS: We found
      that several Prdx genes were strongly expressed in multiciliated cells in
      developing Xenopus embryos, and their peroxidatic functions were crucial for
      normal cilia development. Depletion of Prdx5 increased levels of cellular
      reactive oxygen species (ROS), consequently leading to mitochondrial dysfunction
      and abnormal cilia formation. Proteomic and transcriptomic approaches revealed
      that excessive ROS accumulation on Prdx5 depletion subsequently reduced the
      expression level of pyruvate kinase (PK), a key metabolic enzyme in energy
      production. We further confirmed that the promotor activity of PK was
      significantly reduced on Prdx5 depletion and that the reduction in PK expression
      and its promoter activity led to ciliary defects observed in Prdx5-depleted
      cells. INNOVATION: Our data revealed the novel relationship between ROS and Prdx5
      and the consequent effects of this interaction on vertebrate ciliogenesis. The
      normal process of ciliogenesis is interrupted by the Prdx5 depletion, resulting
      in excessive ROS levels and suggesting cilia as vulnerable targets of ROS.
      CONCLUSION: Prdx5 plays protective roles in mitochondria and is critical for
      normal cilia development by regulating the levels of ROS. The loss of Prdx5 is
      associated with excessive production of ROS, resulting in mitochondrial
      dysfunction and aberrant ciliogenesis.

PMID- 30191721
TI  - Predictive relevance of ncRNAs in non-small-cell lung cancer patients with
      radiotherapy: a review of the published data.
AB  - Radiotherapy is one of the most commonly used methods to treat non-small-cell
      lung cancer. However, radiotherapy, especially thoracic radiotherapy, is always
      accompanied by radiation-induced complications or radioresistance. In this
      regard, ncRNAs, including miRNAs and lncRNAs, have received considerable interest
      for their predictive relevance. This review article illustrates the recent
      findings about the possible involvement of ncRNAs, mainly miRNAs and lncRNAs, in
      radioresistance and radiation-induced complications and their potential use for
      predicting radiation-induced complications and radiotherapy response.

PMID- 30191722
TI  - Adjunctive Internet-delivered cognitive behavioural therapy for insomnia in men
      with depression: A randomised controlled trial.
AB  - OBJECTIVE: Internet-delivered cognitive behavioural therapy for insomnia is
      efficacious for insomnia, and post hoc analyses suggest mood improvements. We
      undertook the first clinical trial evaluating the efficacy of Internet-delivered
      cognitive behavioural therapy for insomnia on depressive symptoms as an adjunct
      to guideline-based treatment of depressive disorders. METHODS: Older men
      undergoing psychiatrist-coordinated treatment for major depressive disorder or
      dysthymia and who had significant insomnia symptoms were randomised to either
      adjunctive Internet-delivered cognitive behavioural therapy for insomnia (Sleep
      Healthy Using The Internet) or online sleep psychoeducation. The primary outcome
      was change in depressive symptoms (Centre for Epidemiological Studies Depression
      scale) from baseline to week 12 (post intervention). Secondary outcomes were
      insomnia and anxiety symptoms. RESULTS: In all, 87 men were randomised (Internet
      delivered cognitive behavioural therapy for insomnia = 45; psychoeducation = 42).
      The mean observed Centre for Epidemiological Studies Depression scale changes by
      week 12 were 8.2 (standard deviation = 11.5) and 3.9 (standard deviation = 12.8)
      for Internet-delivered cognitive behavioural therapy for insomnia and
      psychoeducation, respectively. The adjunctive effect size of 0.35 in favour of
      Sleep Healthy Using The Internet programme was not statistically significant
      (group * time difference in the Mixed effect Model Repeat Measurement analysis
      difference 4.3; 95% confidence interval = [-1.2, 9.8]; p = 0.15). There was a
      statistically significant effect on insomnia symptoms (group * time p = 0.02,
      difference 2.7; 95% confidence interval = [0.2, 5.3]; effect size = 0.62). There
      were no differences in insomnia or depression at 6 months or differential effects
      on anxiety at any time point. There were no reported adverse trial-related events
      in the intervention arm. CONCLUSION: Adjunctive Internet-delivered cognitive
      behavioural therapy for insomnia for older men being treated for depression can
      improve insomnia in the short term, without apparent harm. The short-term
      depressive symptom effect size in this pilot trial was comparable to other
      adjunctive interventions and may warrant a larger, definitive trial.

PMID- 30191723
TI  - Selfitis and behavioural addiction: A plea for terminological and conceptual
      rigour.

PMID- 30191724
TI  - Can antipsychotic medication administered for paediatric emotional and
      behavioural disorders lead to brain atrophy?

PMID- 30191725
TI  - An attempt to discontinue clozapine - Worth a try?

PMID- 30191726
TI  - Biomarkers for diagnosis of pre-eclampsia and endometriosis.
AB  - Gynecological disorders are leading public health problems in developing
      countries with substantial impact on women's quality of life. Significant
      proportion of maternal mortality and reproductive morbidity is attributed to
      misdiagnosis and mismanagement of pregnancy related lethal pathological
      conditions and affect women's health. Timely diagnosis is necessary to prevent
      maternal deaths and to manage complications. Biomarker development will create a
      wide window of opportunity for early diagnosis. This review discusses the current
      status of biomarkers and recent advances in 'omics' technology for early
      screening of endometriosis and pre-eclampsia because of significant global
      bioburden associated with these disorders. This review will also give baseline
      data for future biomarker development strategies.

PMID- 30191727
TI  - A meta-analysis of Italian and Estonian individuals shows an effect of common
      variants in HMGCR on blood apoB levels.
AB  - AIM: The aim of the study was to explore the effects of variants at 3-hydroxy-3
      methylglutaryl-CoA reductase (HMGCR) and kinesin family member 6 (KIF6) loci on a
      range of cardio-metabolic phenotypes. METHODS: We analyzed the range of variants
      within Genetics in Brisighella Health Study and KIF6 genes using an additive
      genetic model on 18 cardiometabolic phenotypes in a sample of 1645 individuals
      from the Genetics in Brisighella Health Study and replicated in 10,662
      individuals from the Estonian Genome Center University of Tartu. RESULTS: We
      defined directly the effects of rs3846662:C>A at HMGCR on apoB levels. The
      analysis also confirmed effects of on low-density lipoprotein-cholesterol and
      total cholesterol levels. Variants in KIF6 gene did not reveal any associations
      with cardiometabolic phenotypes. CONCLUSION: This study highlights effect of
      HMGCR locus on assay-determined apoB levels, an infrequent measure of blood
      lipids in large studies.

PMID- 30191729
TI  - Clinical significance of microRNA-21 expression in disease progression of
      patients with hepatocellular carcinoma.
AB  - AIM: Aberrant microRNA (miR) expression is associated with hepatocellular
      carcinoma (HCC). MATERIALS & METHODS: Here, we investigated the clinical
      significance of miR-21 and miR-31 for HCC-specific prognostic effect. HCC
      patients (n = 93) who underwent liver biopsy or surgical resection were enrolled,
      and HCC tissues and paired adjacent nontumor liver tissues were collected and
      analyzed for miRs expression. RESULTS: MiR-21 expression was significantly
      upregulated in HCC tissues relative to nontumor tissues. Both miR-21 and miR-31
      expression in HCC tissues did not predict overall survival; however, miR-21 was
      considered an independent predictor of disease progression together with portal
      vein thrombosis and higher Barcelona Clinical Liver Cancer stage. CONCLUSION:
      Elevated miR-21 expression might represent a biomarker for HCC prognosis.

PMID- 30191730
TI  - Effect of Nasal Valve Shape on Downstream Volume, Airflow, and Pressure Drop:
      Importance of the Nasal Valve Revisited.
AB  - OBJECTIVES: The relative importance of the nasal valve relative to the remainder
      of the nasal airway remains unknown. The goal of this article was to objectively
      measure the shape of the nasal inlet and its effect on downstream airflow and
      nasal cavity volume using a physical model and a physiologic flow model. METHODS:
      A patient who had isolated nasal valve surgery and had pre- and postoperative
      computed tomography scans available for analysis was studied. Nasal inlet shape
      measurements, computational fluid dynamics, and nasal volume analysis were
      performed using the computed tomography data. In addition, a physical model was
      used to determine the effect of nasal obstruction on downstream soft tissue.
      RESULTS: The postoperative shape of the nasal inlet was improved in terms of
      length and degree of tortuosity. Whereas the operated-on region at the nasal
      inlet showed an only 25% increase in cross-sectional area postoperatively,
      downstream nonoperated sites in the nasal cavity revealed increases in area
      ranging from 33% to 51%. Computational fluid dynamics analysis showed that airway
      resistance decreased by 42%, and pressure drop was reduced by 43%. Intraluminal
      mucosal expansion was found with nasal obstruction in the physical model.
      CONCLUSION: By decreasing the degree of bending and length at the nasal valve,
      inspiratory downstream nonoperated sites of the nasal cavity showed improvement
      in volume and airflow, suggesting that the nasal valve could play an oversized
      role in modulating the aerodynamics of the airway. This was confirmed with the
      physical model of nasal obstruction on downstream mucosa.

PMID- 30191731
TI  - The diagnostic role of circulating inflammation-based biomarker in gallbladder
      carcinoma.
AB  - AIM: To investigate the diagnostic roles of circulating inflammatory biomarkers
      in gallbladder carcinoma (GBC). PATIENTS & METHODS: Circulating inflammatory cell
      count, fibrinogen, albumin, carcinoembryonic antigen (CEA) and CA199 were
      measured, neutrophil-to-lymphocyte ratio (NLR), dNLR, PLR, LMR and Alb-to-fib
      (AFR) were calculated in 306 GBC patients, 306 healthy and 305 benign controls.
      The reciever operating characteristic curve was used to determine diagnostic
      accuracy of them. RESULTS: The area under curves of combined AFR, dNLR and
      lymphocyte were 0.943 and 0.985 for diagnosis of GBC from healthy and polyp
      controls, area under curve of combined AFR, CEA and CA199 was 0.90 for diagnosis
      of GBC from the cholecystitis patients. CONCLUSION: Circulating AFR combined with
      lymphocyte and dNLR or CEA and CA199 could effectively distinguish GBC from the
      healthy and benign controls.

PMID- 30191732
TI  - Response to Johnston re: MRI Displays the Prostatic Cancer Anatomy and Improves
      the Bundles Management Before Robot-Assisted Radical Prostatectomy by Bianchi et
      al. (From: Johnston WK, III. J Endourol 2018;32:322-323).

PMID- 30191728
TI  - Coptisine-induced inhibition of Helicobacter pylori: elucidation of specific
      mechanisms by probing urease active site and its maturation process.
AB  - In this study, we examined the anti-Helicobactor pylori effects of the main
      protoberberine-type alkaloids in Rhizoma Coptidis. Coptisine exerted varying
      antibacterial and bactericidal effects against three standard H. pylori strains
      and eleven clinical isolates, including four drug-resistant strains, with minimum
      inhibitory concentrations ranging from 25 to 50 MUg/mL and minimal bactericidal
      concentrations ranging from 37.5 to 125 MUg/mL. Coptisine's anti-H. pylori
      effects derived from specific inhibition of urease in vivo. In vitro, coptisine
      inactivated urease in a concentration-dependent manner through slow-binding
      inhibition and involved binding to the urease active site sulfhydryl group.
      Coptisine inhibition of H. pylori urease (HPU) was mixed type, while inhibition
      of jack bean urease was non-competitive. Importantly, coptisine also inhibited
      HPU by binding to its nickel metallocentre. Besides, coptisine interfered with
      urease maturation by inhibiting activity of prototypical urease accessory protein
      UreG and formation of UreG dimers and by promoting dissociation of nickel from
      UreG dimers. These findings demonstrate that coptisine inhibits urease activity
      by targeting its active site and inhibiting its maturation, thereby effectively
      inhibiting H. pylori. Coptisine may thus be an effective anti-H. pylori agent.

PMID- 30191733
TI  - Is there a role for biomarkers in pulmonary rehabilitation?

PMID- 30191735
TI  - Sniffing out causes of gastrointestinal disorders: a review of volatile
      metabolomic biomarkers.
AB  - Distinct changes can be observed in the odor of human excretions during health
      and disease. Identifying underlying volatile metabolites responsible for these
      odorous changes can be correlated with the pathological process within the body.
      Advances in the technology have enabled us to interpret the volatile signature of
      these changes in the odor. This has opened a promising area to lay the
      foundations of a rapid, noninvasive and point of care diagnostic tool. This
      review explores the diagnostic potential of volatile organic metabolites as novel
      biomarkers and extends the discussion on the clinical applications of these
      biomarkers in gastrointestinal disorders.

PMID- 30191736
TI  - Screening circular RNA related to chemotherapeutic resistance in osteosarcoma by
      RNA sequencing.
AB  - AIM: To identify circular RNAs (circRNAs) related to osteosarcoma (OS)
      chemoresistance. MATERIALS & METHODS: CircRNA expression profile was performed in
      three paired human chemoresistant and chemosensitive OS cell lines by next
      generation sequencing. Quantitative real-time-PCR (qRT-PCR) was used to confirm
      next-generation sequencing data. Bioinformatics analysis was conducted to predict
      their functions. RESULTS: Eighty circRNAs were dysregulated in the chemoresistant
      OS cells compared with the control, after validated by qRT-PCR. Bioinformatics
      analysis showed that some pathways related to drug metabolism were significantly
      enriched. Additionally, hsa_circ_0004674 was distinctly increased in OS
      chemoresistant cells and tissues, related to poor prognosis. CircRNA-miRNA-mRNA
      pathways related to hsa_circ_0004674 were constructed by TargetScan and miRanda.
      CONCLUSION: CircRNAs may play a role in OS chemoresistance and hsa_circ_0004674
      might be a candidate target.

PMID- 30191734
TI  - In the quest for new targets for pathogen eradication: the adenylosuccinate
      synthetase from the bacterium Helicobacter pylori.
AB  - Adenylosuccinate synthetase (AdSS) is an enzyme at regulatory point of purine
      metabolism. In pathogenic organisms which utilise only the purine salvage
      pathway, AdSS asserts itself as a promising drug target. One of these organisms
      is Helicobacter pylori, a wide-spread human pathogen involved in the development
      of many diseases. The rate of H. pylori antibiotic resistance is on the increase,
      making the quest for new drugs against this pathogen more important than ever. In
      this context, we describe here the properties of H. pylori AdSS. This enzyme
      exists in a dimeric active form independently of the presence of its ligands. Its
      narrow stability range and pH-neutral optimal working conditions reflect the
      bacterium's high level of adaptation to its living environment. Efficient
      inhibition of H. pylori AdSS with hadacidin and adenylosuccinate gives hope of
      finding novel drugs that aim at eradicating this dangerous pathogen.

PMID- 30191737
TI  - Autoantibody against new gene expressed in prostate protein is traceable in
      prostate cancer patients.
AB  - AIM: We assessed an autoantibody against new gene expressed in prostate (NGEP)
      protein for prostate cancer (PCa) that may better diagnosis and prognosis
      approaches in the patients with PCa. METHODS: Autoantibodies against NGEP were
      measured in sera of PCa patients by ELISA. RESULTS: The autoantibody against NGEP
      is present in a significantly higher proportion in the sera of PCa patients as
      compared with healthy controls (p < 0.001). An inverse significant correlation
      was found between seropositive patients and Gleason score (p < 0.05) and serum
      prostate-specific antigen (recombinant NGEP; p < 0.05). CONCLUSION: The data
      showed that measurement of autoantibody against NGEP as a novel prostate-specific
      antigen in sera can be used as a potential biomarker to discriminate well
      differentiated PCa patients from normal subjects.

PMID- 30191739
TI  - Survival strategies of cancerous cells: a novel perspective.

PMID- 30191740
TI  - Decoding the LncRNA transcriptome of esophageal cancer: identification of
      clinically relevant LncRNAs.
AB  - AIM: LncRNAs may act as promising biomarkers in esophageal cancer (EC). Here, we
      illustrate the LncRNA profile and their clinical relevance in EC. PATIENTS &
      METHODS: In this study, we utilized the Cancer Genome Atlas RNA-sequencing and
      clinical data from 186 patients and 13 normal samples. Various statistical and
      gene set enrichment analysis (GSEA) were performed to identify the biomarkers.
      RESULTS: In a differential expression analysis, we identified a total of 127
      LncRNAs with more differentially expressed in EC compared with normal and showed
      their function using guilt-by-association analysis. We generated a LncRNAs
      prognostic signature for EC. Using Cox regression analysis, we showed the
      prognostic ability of LncRNAs' prognostic signature in training and test-cohort
      (p-value < 0.01). CONCLUSION: In summary, we explored the LncRNA expression
      profile and their clinical utility in EC patients.

PMID- 30191738
TI  - Novel group of tyrosyl-DNA-phosphodiesterase 1 inhibitors based on disaccharide
      nucleosides as drug prototypes for anti-cancer therapy.
AB  - A new class of tyrosyl-DNA phosphodiesterase 1 (TDP1) inhibitors based on
      disaccharide nucleosides was identified. TDP1 plays an essential role in the
      resistance of cancer cells to currently used antitumour drugs based on Top1
      inhibitors such as topotecan and irinotecan. The most effective inhibitors
      investigated in this study have IC50 values (half-maximal inhibitory
      concentration) in 0.4-18.5 uM range and demonstrate relatively low own
      cytotoxicity along with significant synergistic effect in combination with anti
      cancer drug topotecan. Moreover, kinetic parameters of the enzymatic reaction and
      fluorescence anisotropy were measured using different types of DNA-biosensors to
      give a sufficient insight into the mechanism of inhibitor's action.

PMID- 30191741
TI  - A Novel Endoluminal Ultrasound Imaging Technique to Determine Urethral Luminal
      Cross-sectional Area.
AB  - INTRODUCTION AND OBJECTIVES: Retrograde urethrogram (RUG) and voiding
      cystourethrogram (VCUG) are currently the gold standard imaging technique for
      diagnosis of urethral stricture and determination of stricture location. However,
      RUG and VCUG have multiple limitations. These techniques require exposure to
      ionizing radiation, the quality is operator and patient dependent, there is a
      moderate degree of invasiveness with urethral catheterization, can have artifacts
      because of patient positioning that underestimates stricture length. The
      development of novel imaging modalities without ionizing radiation to accurately
      evaluate the presence, location, length, and lumen cross-sectional area (CSA) of
      the urethral stricture would be of great value. The objective of this study was
      to develop a novel endoluminal ultrasound (ELUS) imaging technique that permits
      the accurate quantitation of urethral stricture. METHODS: Urethral strictures
      were created in rabbits (n = 5) by electrocautery and an ELUS technique was
      developed for subsequent luminal imaging. A 3.2F 40 MHz ultrasound (US) probe was
      introduced transurethrally and infused with US contrast agent. Images were
      recorded as the catheter was pulled back at a constant speed to acquire
      tomographic images. Lumen CSA over the entire urethral length was calculated
      using a custom methodology and validated in our laboratory. RESULTS: Urethral
      luminal CSA over the entire length of urethra before and after experimental
      stricture development was quantified including the length of stenosis. Intra- and
      interobserver variability (r = 0.99 for both) was excellent. CONCLUSIONS:
      Feasibility of ELUS as a quantitative technique to determine healthy urethral
      lumen and stricture CSA was demonstrated. The translational potential for a
      nonionizing imaging modality to better describe CSA, length, location, and
      uninvolved urethral CSA of the stricture is a significant improvement over
      current methodology.

PMID- 30191742
TI  - NT-proBNP levels and mortality in a general population-based cohort from Turkey:
      a long-term follow-up study.
AB  - AIM: We investigated the relationship between NT-ProBNP and mortality in a
      general population-based cohort. METHODS & RESULTS: A total of 2021 out of 4650
      participants from previously published HAPPY study were included. Mean follow-up
      was 84.5 +/- 10.4 months. After adjusting for risk factors, high levels of LogNT
      proBNP predicted all-cause death (HR: 3.23; 95% CI: 2.20-4.75; p < 0.001) and
      cardiovascular death (HR: 3.85; 95% CI: 2.37-6.26; p < 0.001). Regression
      analysis revealed that LogNT-proBNP was an independent predictor of all-cause
      death (HR: 2.85; 95% CI: 1.91-4.24; p < 0.001) and cardiovascular death (HR:
      3.02; 95% CI: 1.84-4.95; p < 0.001). Conclusion: Our study showed that in long
      term follow-up, NT-proBNP is associated with increased all-cause and
      cardiovascular mortality.

PMID- 30191743
TI  - Targeting of Influenza Viral Epitopes to Antigen-Presenting Cells by Genetically
      Engineered Chimeric Molecules in a Humanized NOD SCID Gamma Transfer Model.
AB  - Antiviral DNA vaccines are a novel strategy in the vaccine development field,
      which basically consists of the administration of expression vectors coding viral
      antigen sequences into the host's cells. Targeting of conserved viral epitopes by
      antibody fragments specific to activating cell surface co-receptor molecules on
      antigen-presenting cells could be an alternative approach for inducing protective
      immunity. It has been shown that FcgammaRI on human monocytes enhances antigen
      presentation in vivo. Various DNA constructs, encoding a Single-chain variable
      antibodies (scFv) from mouse anti-human FcgammaRI monoclonal antibody, coupled to
      a sequence encoding a T- and B-cell epitope-containing influenza A virus
      hemagglutinin inter-subunit peptide were inserted into the eukaryotic expression
      vector system pTriEx-3 Neo. The constructed chimeric DNA molecules were expressed
      by transfected Chinese hamster ovary cells and the ability of the engineered
      proteins to interact with FcgammaRI-expressing cells was confirmed by flow
      cytometry. The fusion protein induced a strong signal transduction on human
      monocytes via FcgammaRI. The expression vector pTriEx-3 Neo containing the
      described construct was used as a naked DNA vaccine and introduced directly to
      experimental humanized NOD SCID gamma mice with or without boosting with the
      expressed fusion protein. Immunization with the generated DNA chimeric molecules
      and prime-boost with the expressed recombinant proteins induced significant serum
      levels of anti-influenza immunoglobulin G antibodies and strong cytotoxic T
      lymphocyte activity against influenza virus-infected cells in humanized animals.

PMID- 30191745
TI  - Oxidative stress-linked biomarkers in idiopathic pulmonary fibrosis: a systematic
      review and meta-analysis.
AB  - AIM: The aim of this meta-analysis was to investigate associations between
      idiopathic pulmonary fibrosis (IPF) and markers of oxidative stress (OS) measured
      in different biological samples. METHODS: A systematic search of publications
      listed in PubMed, Web of Science, Scopus and Google Scholar from inception to
      December 2017 was conducted. RESULTS: Significant differences between IPF
      patients and controls were observed for all biomarkers (thiobarbituric acid
      reactive substances, hydroperoxides and glutathione), barring systemic
      isoprostanes. CONCLUSION: This meta-analysis showed a consistent increase in the
      concentrations of OS markers or a reduction in antioxidant markers, in patients
      with IPF, independent of the type of biological sample. Pending the results of
      further studies, OS biomarkers might be useful for the diagnosis and monitoring
      of IPF.

PMID- 30191744
TI  - Design, synthesis, and screening of ortho-amino thiophene carboxamide derivatives
      on hepatocellular carcinomaas VEGFR-2Inhibitors.
AB  - In this work, design, synthesis, and screening of thiophene carboxamides 4-13 and
      16-23 as dual vascular endothelial growth factor receptors (VEGFRs) and mitotic
      inhibitors was reported. All compounds were screened against two gastrointestinal
      solid cancer cells, HepG-2 and HCT-116 cell lines. The most active cytotoxic
      derivatives 5 and 21 displayed 2.3- and 1.7-fold higher cytotoxicity than
      Sorafenib against HepG-2 cells. Cell cycle and apoptosis analyses for compounds 5
      and 21 showed cells accumulation in the sub-G1 phase, and cell cycle arrest at
      G2/M phase. The apoptotic inducing activities of compounds 5 and 21were
      correlated to the elevation of p53, increase in Bax/Bcl-2 ratio, and increase in
      caspase-3/7.Compounds 5 and 21 showed potent inhibition againstVEGFR-2 (IC50 =
      0.59 and 1.29 MUM) and beta-tubulin polymerization (73% and 86% inhibition at
      their IC50 values).Molecular docking was performed with VEGFR-2 and tubulin
      binding sites to explain the displayed inhibitory activities.

PMID- 30191746
TI  - Light, Alertness, and Alerting Effects of White Light: A Literature Overview.
AB  - Light is known to elicit non-image-forming responses, such as effects on
      alertness. This has been reported especially during light exposure at night.
      Nighttime results might not be translatable to the day. This article aims to
      provide an overview of (1) neural mechanisms regulating alertness, (2) ways of
      measuring and quantifying alertness, and (3) the current literature specifically
      regarding effects of different intensities of white light on various measures and
      correlates of alertness during the daytime. In general, the present literature
      provides inconclusive results on alerting effects of the intensity of white light
      during daytime, particularly for objective measures and correlates of alertness.
      However, the various research paradigms employed in earlier studies differed
      substantially, and most studies tested only a limited set of lighting conditions.
      Therefore, the alerting potential of exposure to more intense white light should
      be investigated in a systematic, dose-dependent manner with multiple correlates
      of alertness and within one experimental paradigm over the course of day.

PMID- 30191747
TI  - Patient-specific mobility assessment to monitor recovery after total hip
      arthroplasty.
AB  - Total hip arthroplasty is a ubiquitously successful orthopedic surgical
      procedure, whose prevalence is rising worldwide. While many investigations focus
      on characterizing periprosthetic pathophysiology, the objective of our research
      is to develop and describe multi-metric assemblies as a first step toward
      creating a patient-specific mobility index that rehabilitators and orthopedic
      surgeons can utilize for prescribing their respective procedures. In total, 48
      total hip arthroplasty patients (both cemented and uncemented) undergoing
      unilateral, primary surgery went through computed tomographic scans and gait
      analysis measurements both before and 1 year following their surgery. Altogether,
      the reported quantitative metrics include 11 spatial and temporal gait
      parameters, muscle density, and electromyography signals from the rectus femoris,
      vastus lateralis, and vastus medialis, and bone mineral density values from
      bioimage analysis around the implant stem. We found that measured parameters from
      a subgroup were sensitive to changes observed during patient recovery,
      implicating the predictive sensitivity of these patient conditions. Most post
      operative gait parameters changed significantly, while electromyography data
      indicated few significant differences. Moreover, results from bioimage analyses
      indicate a general reduction of periprosthetic bone mineral density after 1 year,
      in association with increasing density of the quadriceps muscles. Furthermore,
      this work identifies which quantitative metrics undergo the greatest variation
      after total hip arthroplasty and demonstrates the clinical feasibility of a
      multimodal approach to mobility assessment that may ultimately support decision
      making for post-surgical rehabilitation protocols.

PMID- 30191748
TI  - Validation of the French Version of the Weiss Functional Impairment Rating Scale
      Self-Report in a Large Cohort of Adult Patients With ADHD.
AB  - OBJECTIVE: To analyze the psychometric properties of the French version of the
      Weiss Functional Impairment Rating Scale-Self Report (WFIRS-S) in a large
      clinical sample of adults with ADHD. METHOD: Patients ( N = 363) were diagnosed
      with ADHD according to the Diagnostic and Statistical Manual of Mental Disorders
      (5th ed.; DSM-5) criteria. Psychometric properties of the French version of the
      WFIRS-S were tested including construct validity with a confirmatory factor
      analysis, internal structural validity with Cronbach's alpha coefficient,
      external validity by correlations with the Beck Depression Inventory-II (BDI-II),
      and the EuroQol five-dimension (EQ-5D) questionnaire. RESULTS: The confirmatory
      factor analysis found the following: root mean square error of approximation
      (RMSEA) = 0.061, 90% confidence interval (CI) = [0.058, 0.063]; comparative fit
      index (CFI) = 0.67. Cronbach's alpha coefficient was .91. Correlations with EQ-5D
      descriptive index, visual analogue scale (VAS) scores, and BDI-II scores were 
      0.48, -0.55, and 0.53, respectively. CONCLUSION: The French version of the WFIRS
      S is a psychometrically acceptable self-reported questionnaire for the multi
      domain evaluation of functional impairments in adults with ADHD, for research and
      clinical purposes.

PMID- 30191749
TI  - Attrition among HIV positive children enrolled under integrated HIV care
      programme in Myanmar: 12 years cohort analysis.
AB  - BACKGROUND: In Myanmar, HIV seropositive children are being enrolled in an
      integrated HIV care (IHC) Program for HIV treatment and care since 2005.
      OBJECTIVES: To assess the: (a) attrition (death or loss-to-follow-up) rates among
      children (aged >= 18 months to < 15 years) enrolled into the programme before and
      after initiation of anti-retroviral therapy (ART) (pre-ART and ART periods); (b)
      demographic and clinical factors associated with attrition during these two
      periods. METHODS: Children enrolled in IHC Programme and their status (death,
      lost to follow-up, regular follow-up or transferred out) was assessed as on 30
      June 2017. Attrition rates (per 100 person-years) at pre - ART and ART periods
      were calculated and the association between demographic and clinical
      characteristics with attrition was assessed using Cox proportional hazards model.
      RESULTS: Among 2,736 children enrolled, pre-ART attrition rate was 19 per 100
      person-years of follow-up (95% CI: 17-21) and ART attrition rate was 4 per 100
      person-years of follow-up (95% CI: 3-4) with higher levels during the initial few
      months of enrolment. The 36-month retention rates during pre-ART period was 75%
      (95% CI: 72-78) and during ART period was 87% (95% CI: 86-88). The children 'at
      enrolment' with relatively lower levels of haemoglobin, immune deficiency,
      underweight for age, higher WHO clinical stages, presence of hepatitis B
      infection had higher hazards of attrition in both periods. CONCLUSION: The
      attrition rates are high particularly among children with relatively poorer
      clinical, nutritional profiles at enrolment. The study suggests the urgent need
      for improving adherence counselling especially during the initial few months of
      enrolment and early ART initiation.

PMID- 30191750
TI  - Parks, Playgrounds, and Incidents of Sexual Assault.
AB  - In the United States, certain laws restrict those convicted of sexually offending
      from accessing social spaces where youth congregate such as parks and
      playgrounds. However, empirical work to date has rarely described sexual assaults
      in these locations or tested the assumptions of these laws explicitly. To address
      these gaps in the literature, we drew on the National Incident-Based Reporting
      System (NIBRS) to analyze offender, victim, and crime characteristics of sexual
      assaults that occurred at parks and playgrounds over a 5-year period (2010-2015).
      Estimated via multivariate logistic regression, results showed support for these
      law's assumptions when analyzing this particular location. However, stranger
      perpetrators were significantly more likely to sexually assault adult victims
      versus youth victims. Several other offense features distinguished youth versus
      adult victim sexual assault incidents at parks and playgrounds, such as the
      offender age, the use of force, and the injuries sustained by the victim.
      Collectively, these findings both support and challenge these types of social
      space restriction laws.

PMID- 30191751
TI  - Peer Victimization in Children With ADHD: A Community-Based Longitudinal Study.
AB  - OBJECTIVES: To investigate (a) whether children with ADHD experience higher
      levels of overt and relational peer victimization (PV) than children without ADHD
      and (b) child, family, and school predictors of PV in children with ADHD. METHOD:
      173 children with ADHD and 199 non-ADHD controls were recruited through 43
      Melbourne schools at mean age 7.3 years. Parent- and teacher-reported PV (Social
      Experience Questionnaire) data were collected at mean age 8.9 years. Potential
      child, family, and school predictors of PV were measured at baseline. RESULTS:
      Children with ADHD experienced higher levels of PV than children without ADHD by
      both parent- and teacher-report. Child predictors accounted for the greatest
      variance in PV, and the strongest predictors of PV were teacher-reported conduct
      problems, and medication use. CONCLUSION: Children with ADHD are at higher risk
      of PV compared with non-ADHD controls. Recognizing and addressing PV is important
      to reduce additional impairment in children with ADHD.

PMID- 30191752
TI  - MicroRNA-520a suppresses HBV replication in HepG2.2.15 cells by inactivating AKT.
AB  - OBJECTIVE: To investigate whether the mechanism by which a microRNA, miR-520a,
      suppresses the replication of hepatitis B virus (HBV) involves the regulation of
      the serine/threonine kinase ( AKT) gene. METHODS: The effects of miR-520a on the
      proliferation, mitotic index and apoptosis of the HBV-replicating human
      hepatocellular carcinoma cell line HepG2.2.15 were measured using standard
      laboratory methods including flow cytometry. The effects of miR-520a on HBV
      transcription and replication were assessed using methods including immunoassays
      and reverse transcription-polymerase chain reaction. The effect of small
      interfering RNA (siRNA) to AKT on the levels of AKT mRNA and protein were also
      evaluated. RESULTS: In HepG2.2.15 cells, miRNA-520a reduced HBV transcription and
      replication by reducing AKT levels. MiRNA-520a decreased cell proliferation and
      mitosis entry of cells and increased apoptosis in HepG2.2.15 cells. AKT levels
      were reduced significantly by its siRNA, which resulted in suppression of HBV
      replication in HepG2.2.15 cells. CONCLUSIONS: MiRNA-520a inhibited AKT gene
      expression and suppressed HBV transcription and replication. These findings
      suggest that miRNA-520a may be a novel target for the treatment of HBV infection
      because miRNA-520a reduced HepG2.2.15 cell survival and inhibited HBV replication
      associated with the AKT signalling pathway.

PMID- 30191753
TI  - The Social Determinants of Nursing Retention in a Pediatric Hematology/Oncology
      Unit.
AB  - Pediatric hematology/oncology units (PHOUs) are highly paced, stressful
      environments and can be difficult areas to work. Thus, these units can present
      issues when it comes to both recruiting and retaining health care professionals
      (HCPs). There is scant research addressing how the environment of a PHOU
      contribute to a HCP's desire to stay or leave this environment. To conduct this
      project, a critical ethnographic approach was used. The researcher conducted
      semistructured interviews ( n = 29), which included nurses ( n = 21), physicians
      ( n = 4), and allied health care staff ( n = 4). This sample represented
      approximately one third of staff in each category. Participants identified that
      their ability to develop long-term relationships with children and families as a
      significant source of satisfaction. Belonging to the oncology team was seen as
      extraordinarily important to all the participants. The majority of the
      participants also felt that working in this ever-evolving dynamic medical field
      afforded them with ongoing learning opportunities. The main frustration described
      by participants pertained to administrative involvement in the everyday workings
      of the PHOU, potentially leading to attrition. It is important to note that there
      was also diversity among and between the categories of HCPs when describing the
      work environment and the issues that most influence them. While similarities
      among participants were found between satisfaction and dissatisfaction,
      significant differences between them led us to believe it would be unreasonable
      to attempt to compare the three groups here. Thus, in this article the author
      focused primarily on nursing while noting related observations from physicians
      and allied health professions.

PMID- 30191754
TI  - In vitro study of antimicrobial and cell viability on newly synthesized bioglass
      based bone grafts: Effects of selenium and silver additions.
AB  - Selenium (Se)- and Silver (Ag)-doped Bioglass(r)-based biografts were synthesized
      using the sol-gel method. Fourier-transform infrared spectroscopy, inductively
      coupled plasma mass spectrometry, scanning electron microscopy and energy
      dispersive X-ray analyses were carried out in order to examine mechanostructure
      of synthesized bioglass-based bioceramics. The effects of Se and Ag additions on
      cell viability were investigated via cytotoxicity and antibacterial activity
      analysis, respectively. The bacteria of Escherichia coli ( E. coli, JM103) and
      Gram-positive Staphylococcus aureus ( S. aureus, ATCC29293) were used to perform
      the antibacterial tests. Moreover, cell viability studies were conducted using
      the Saos-2 osteoblast cells by performing dimethylthiazol diphenyltetrazolium
      bromide assay. It was observed that while (PO4)3- and (CO3)2- peaks were observed
      in Fourier-transform infrared spectroscopy analyses, crystallinity also increased
      with increasing amount of AgNO3 addition into the Bioglass(r). In addition, it
      was determined from scanning electron microscopy images that small irregular thin
      lamellar grain distribution was formed in synthesized B45Ag5Se20 and B30Ag10Se15
      biografts. From antibacterial activity tests, it was determined that while some
      grafts was affected by E. coli, which is a Gram-negative, however, some did not
      affect the Gram-positive S. aureus and had antimicrobial activity on E. coli and
      S. aureus. According to the cell viability tests, it was found that the
      synthesized grafts did not have toxic effect on living cells. While the cell
      growth was greater for some grafts, however, some others had lower growth.

PMID- 30191759
TI  - Late stent thrombosis in a patient with CYP2C19*3/*17 genotype and clopidogrel
      high on-treatment platelet reactivity.
AB  - AIM: Recurrent thrombotic events still occur despite dual antiplatelet therapy in
      patient's post percutaneous coronary intervention (PCI) could be attributed to
      high on-treatment platelet reactivity. METHODS: A 44-year-old male, who had
      staged PCI to left anterior descending (LAD) 2 weeks after an anterior MI, with a
      drug-coated stent was readmitted with new anterior STEMI 35 days later. Coronary
      angiogram revealed mid-stent thrombus in situ. He had further uncomplicated PCI.
      Platelet function testing and genotyping showed clopidogrel high on-treatment
      platelet reactivity and CYP2C19*3/*17 genotype. Ticagrelor was commenced. RESULTS
      & CONCLUSION: This case study is the first reported in Malaysia to document a
      patient with a CYP2C19*3/*17 genotype presenting with a stent thrombosis after an
      uncomplicated index PCI procedure.

PMID- 30191755
TI  - Comparison of Short-Term Outcomes Between Robotic-Assisted and Laparoscopic
      Surgery in Colorectal Cancer.
AB  - AIM: The robotic technique has been established as an alternative approach to
      laparoscopy in colorectal surgery. The aim of this study was to compare short
      term outcomes of robot-assisted and laparoscopic surgery in colorectal cancer.
      METHODS: The cases of robot-assisted or laparoscopic colorectal resection were
      collected retrospectively between July 2015 and October 2017. We evaluated
      patient demographics, perioperative characteristics, and pathologic examination.
      A multivariable linear regression model was used to assess short-term outcomes
      between robot-assisted and laparoscopic surgery. Short-term outcomes included
      time to passage of flatus and postoperative hospital stay. RESULTS: A total of
      284 patients were included in the study. There were 104 patients in the robotic
      colorectal surgery (RCS) group and 180 in the laparoscopic colorectal surgery
      (LCS) group. The mean age was 60.5 +/- 10.8 years, and 62.0% of the patients were
      male. We controlled for confounding factors, and then the multiple linear model
      regression indicated that the time to passage of flatus in the RCS group was 3.45
      days shorter than the LCS group (coefficient = -3.45, 95% confidence interval
      [CI] = -5.19 to -1.71; P < .001). Additionally, the drainage of tube duration
      (coefficient = 0.59, 95% CI = 0.3 to 0.87; P < .001) and transfers to the
      intensive care unit (coefficient = 7.34, 95% CI = 3.17 to 11.5; P = .001)
      influenced the postoperative hospital stay. The total costs increased by 15501.48
      CNY in the RCS group compared with the LCS group ( P = .008). CONCLUSIONS: The
      present study suggests that colorectal cancer robotic surgery was more beneficial
      to patients because of shorter postoperative recovery time of bowel function and
      shorter hospital stays.

PMID- 30191760
TI  - A new era for stroke therapy: Integrating neurovascular protection with optimal
      reperfusion.
AB  - Recent advances in stroke reperfusion therapies have led to remarkable
      improvement in clinical outcomes, but many patients remain severely disabled, due
      in part to the lack of effective neuroprotective strategies. In this review, we
      show that 95% of published preclinical studies on "neuroprotectants" (1990-2018)
      reported positive outcomes in animal models of ischemic stroke, while none
      translated to successful Phase III trials. There are many complex reasons for
      this failure in translational research, including that the majority of clinical
      trials did not test early delivery of neuroprotectants in combination with
      successful reperfusion. In contrast to the clinical trials, >80% of recent
      preclinical studies examined the neuroprotectant in animal models of transient
      ischemia with complete reperfusion. Furthermore, only a small fraction of
      preclinical studies included long-term functional assessments, aged animals of
      both genders, and models with stroke comorbidities. Recent clinical trials
      demonstrate that 70%-80% of patients treated with endovascular thrombectomy
      achieve successful reperfusion. These successes revive the opportunity to retest
      previously failed approaches, including cocktail drugs that target multiple
      injury phases and different cell types. It is our hope that neurovascular
      protectants can be retested in future stroke research studies with specific
      criteria outlined in this review to increase translational successes.

PMID- 30191761
TI  - White Light During Daytime Does Not Improve Alertness in Well-rested Individuals.
AB  - Broad-spectrum light applied during the night has been shown to affect alertness
      in a dose-dependent manner. The goal of this experiment was to investigate
      whether a similar relationship could be established for light exposure during
      daytime. Fifty healthy participants were subjected to a paradigm (0730-1730 h) in
      which they were intermittently exposed to 1.5 h of dim light (<10 lux) and 1 h of
      experimental light (24-2000 lux). The same intensity of experimental light was
      used throughout the day, resulting in groups of 10 subjects per intensity.
      Alertness was assessed with subjective and multiple objective measures. A
      significant effect of time of day was found in all parameters of alertness ( p <
      0.05). Significant dose-response relationships between light intensity and
      alertness during the day could be determined in a few of the parameters of
      alertness at some times of the day; however, none survived correction for
      multiple testing. We conclude that artificial light applied during daytime at
      intensities up to 2000 lux does not elicit significant improvements in alertness
      in non-sleep-deprived subjects.

PMID- 30191762
TI  - Augmentation Cystoplasty of Diseased Porcine Bladders with Bi-Layer Silk Fibroin
      Grafts.
AB  - The ability of bi-layer silk fibroin (BLSF) matrices to mediate functional tissue
      formation in porcine bladders subjected to acute partial bladder outlet
      obstruction (pBOO) was investigated. Sixteen female swine were fitted with a
      transient urinary catheter containing controlled release valves capable of
      producing either mild (m-pBOO, 35 +/- 10 cmH2O, N = 5) or severe (s-pBOO, 70 +/-
      15 cmH2O, N = 11) urinary outlet resistance for 2 or 4 weeks, respectively. After
      obstructive insults, augmentation cystoplasty was performed with BLSF grafts and
      animals were harvested up to 3 months postrepair. Urodynamic evaluations of swine
      after m-pBOO and s-pBOO injury displayed significant reductions in bladder
      capacity reflecting 63% +/- 19% and 39% +/- 13% of noninjured levels, while the s
      pBOO cohort demonstrated a 61% decline in bladder compliance from baseline. By 3
      months postreconstruction, bladder capacity and compliance in the augmented s
      pBOO group were significantly increased over post-pBOO values reflecting 79% +/-
      19% and 171% +/- 75% of baseline quantities, respectively. Neotissues with
      contractile properties were present at graft sites in both injury groups and
      displayed SM22alpha+ smooth muscle, pan-cytokeratin+ epithelia, vessels lined
      with CD31+ endothelial cells, and neurofilament 200+ nerve trunks. We demonstrate
      that BLSF scaffolds can support improvements in bladder capacity and compliance
      and promote the formation of neotissues in diseased bladders.

PMID- 30191763
TI  - Factor VII deficiency - an enigma; clinicohematological profile in 12 cases.
AB  - OBJECTIVE: Factor VII deficiency is the commonest of the rare bleeding disorders
      with limited knowledge on clinical profile. The objective of this study was to
      study the prevalence and clinico-hematological profile of factor VII-deficient
      patients. METHODS: It is a retrospective observational study of probable
      inherited factor VII deficiency covering 18 months. Their clinical profile,
      family history, investigation and treatment records were studied in detail.
      RESULTS: The study group comprised of total 12 factor VII deficiency cases with
      mean age of 17.5 years of onset of symptoms. The commonest symptom was
      menorrhagia (41.6%) followed by epistaxis (25%) and easy bruisability (16.6%).
      These 12 patients when categorized according to bleeding severity: severe
      bleeding - 2, moderate bleeding - 3, mild bleeding - 6 and asymptomatic - 1. All
      cases had prolonged prothrombin time (PT) with mean PT of 35.4 seconds (range 18
      50 seconds) and mean prolongation of PT from upper limit of normal - 19.4 seconds
      (range 2-34 seconds). Factor VII levels ranged from < 1-40% in these patients.
      Clinical symptoms were not in concordance with factor levels. Of 12 patients,
      required treatment other than local measures. DISCUSSION AND CONCLUSION:
      Inherited factor VII deficiency is the commonest autosomally inherited factor
      deficiency with marked variation in the age of presentation and clinical
      symptoms. The laboratory results in form of PT and factor VII levels do not
      correlate with the severity of clinical presentation. A comprehensive evaluation
      to exclude acquired causes of factor VII deficiency, e.g. obesity, liver
      diseases, vitamin K deficiency and acquired inhibitors is required before
      labeling it as inherited in the absence of family history and molecular studies.

PMID- 30191764
TI  - Inhalable lactoferrin-chondroitin nanocomposites for combined delivery of
      doxorubicin and ellagic acid to lung carcinoma.
AB  - AIM: The use of inhalable nanomedicines can overcome the Enhanced permeation and
      retention effect (EPR)-associated drawbacks in lung cancer therapy via systemic
      nanomedicines. METHODS: We developed a lactoferrin-chondroitin sulfate
      nanocomplex for the co-delivery of doxorubicin and ellagic acid nanocrystals to
      lung cancer cells. Then, the nanocomplex was converted into inhalable
      nanocomposites via spray drying. RESULTS: The resulting 192.3 nm nanocomplex
      exhibited a sequential faster release of ellagic acid, followed by doxorubicin.
      Furthermore, the nanocomplex demonstrated superior cytotoxicity and
      internalization into A549 lung cancer cells mediated via Tf and CD44 receptors.
      The inhalable nanocomposites exhibited deep lung deposition (89.58% fine particle
      fraction [FPF]) with powerful antitumor efficacy in lung cancer bearing mice.
      CONCLUSION: Overall, inhalable lactoferrin-chondroitin sulfate nanocomposites
      would be a promising carrier for targeted drug delivery to lung cancer.

PMID- 30191765
TI  - Temporary Reversal of Blood Flow During Transcarotid Artery Revascularization
      Does Not Change Brain Electrical Activity in Lead-In Cases of the ROADSTER 1
      Multicenter Trial.
AB  - PURPOSE: To evaluate any intraoperative electroencephalographic (EEG) changes
      accompanying reversed flow with the ENROUTE Transcarotid Neuroprotection System
      during transcarotid artery revascularization (TCAR). METHODS: A post hoc analysis
      was performed of the first 81 consecutive lead-in patients (mean age 72.8+/-8
      years; 61 men) enrolled in the ROADSTER 1 trial at 5 participating institutions.
      All patients had high-grade carotid artery stenosis [53 (59.3%) left sided; 12
      (14.8%) contralateral occlusions] and high-risk criteria for carotid
      endarterectomy. A third had symptoms of either stroke (13, 16.0%) or transient
      ischemic attack (14, 17.3%). This subset of early patients underwent EEG
      monitoring to detect any cerebral changes during reversed flow as an added safety
      measure mandated by the ROADSTER 1 trial protocol. RESULTS: Mean flow reversal
      time was 12.9+/-8.2 minutes. The goal mean arterial pressure during reversed flow
      was 100 mm Hg, but 7 (8.6%) patients suffered hypotension. One (1.2%) patient had
      slight EEG changes secondary to blood pressure fluctuation; these resolved with
      blood pressure elevation. No other EEG changes were noted. One (1.2%) patient had
      a postoperative stroke and another (1.2%) had postoperative myocardial infarction
      (MI), leading to 2.5% 30-day stroke/death/MI rate. CONCLUSION: Temporary reversal
      of blood flow during TCAR is a safe maneuver and does not cause cerebral ischemia
      in the vast majority of patients, including those with contralateral carotid
      occlusion. Carotid stenting performed with reversed blood flow mitigates cerebral
      embolization and periprocedural stroke without concern for brain ischemia.

PMID- 30191766
TI  - Genetic risk factors for VIPN in childhood acute lymphoblastic leukemia patients
      identified using whole-exome sequencing.
AB  - AIM: To identify genetic markers associated with vincristine-induced peripheral
      neuropathy (VIPN) in childhood acute lymphoblastic leukemia. PATIENTS & METHODS:
      Whole-exome sequencing data were combined with exome-wide association study to
      identify predicted-functional germline variants associated with high-grade VIPN.
      Genotyping was then performed for top-ranked signals (n = 237), followed by
      validation in independent replication group (n = 405). RESULTS: Minor alleles of
      rs2781377/SYNE2 (p = 0.01) and rs10513762/MRPL47 (p = 0.01) showed increased
      risk, whereas that of rs3803357/BAHD1 had a protective effect (p = 0.007). Using
      a genetic model based on weighted genetic risk scores, an additive effect of
      combining these loci was observed (p = 0.003). The addition of rs1135989/ACTG1
      further enhanced model performance (p = 0.0001). CONCLUSION: Variants in SYNE2,
      MRPL47 and BAHD1 genes are putative new risk factors for VIPN in childhood acute
      lymphoblastic leukemia.

PMID- 30191768
TI  - A Concealed "Natural Orifice": Umbilicus Anatomy for Minimally Invasive Surgery.
AB  - INTRODUCTION: A recent development in minimally invasive surgery (MIS) is single
      port surgery, where a single large multiport trocar is placed in the umbilicus.
      All medical schools require that students complete an anatomy course as part of
      the medical curriculum. However, there is limited instruction regarding the
      detailed parts of the "umbilicus." In several famous anatomy atlases, the
      umbilicus is not dissected at all and is merely represented as a button. Until
      now, the true nature of the umbilicus has not been anatomically demonstrated.
      METHODS: Five cadavers were obtained from the Osaka Medical College medical
      student anatomy class. The umbilicus was dissected in the anatomy laboratory, to
      demonstrate all the layers. A detailed dissection was performed, focusing on the
      exact center of the umbilicus, in order to ascertain whether there exists a
      "natural orifice" or a fascial defect. RESULTS: In all cadavers, a small defect
      of fascia was identified just below the center of the umbilicus. Yellow fatty
      tissue was present just below the skin in the exact center of the umbilicus. A
      probe placed exactly in the middle of this defect passes easily through into the
      abdominal cavity. CONCLUSIONS: With the widespread use of MIS, umbilical incision
      is commonly used to reduce pain and improve cosmetic results. This study
      consistently revealed a natural defect of fascia in the center of the umbilicus.
      Therefore, the umbilicus can be called a concealed "natural orifice." It is
      important to recognize and utilize this defect effectively to minimize
      unnecessary tissue trauma during MIS.

PMID- 30191769
TI  - Do Developmental and Life-Course Theory Risk Factors Equally Predict Age of Onset
      Among Juvenile Sexual and Nonsexual Offenders?
AB  - Previous empirical inquiries into the etiology of juvenile sex offending have
      been largely atheoretical. Consequently, a call for studies conducted utilizing
      developmental and life-course (DLC) criminological theory has been made to better
      understand the onset, development, risk, and protective factors of juvenile sex
      offending. Therefore, this study contributes to the discussion by testing key
      predictions proposed by the DLC framework regarding the theoretical correlates of
      early onset offending, as applied to juvenile sex offenders (JSOs) and juvenile
      nonsex offenders (JNSOs). Drawing on a data set of more than 64,000 youth
      referred to the Florida Department of Juvenile Justice, results indicate that
      although the number and severity of risk factors for early age of onset differ
      between the JSOs and JNSOs, the specific type of risk factors that emerged align
      with DLC theory predictions. The implications of these findings and contributions
      for DLC theory are also discussed.

PMID- 30191767
TI  - Self-Adjusted Amplification Parameters Produce Large Between-Subject Variability
      and Preserve Speech Intelligibility.
AB  - The current study used the self-fitting algorithm to allow listeners to self
      adjust hearing-aid gain or compression parameters to select gain for speech
      understanding in a variety of quiet and noise conditions. Thirty listeners with
      mild to moderate sensorineural hearing loss adjusted gain parameters in quiet and
      in several types of noise. Outcomes from self-adjusted gain and audiologist-fit
      gain indicated consistent within-subject performance but a great deal of between
      subject variability. Gain selection did not strongly affect intelligibility
      within the range of signal-to-noise ratios tested. Implications from the findings
      are that individual listeners have consistent preferences for gain and may prefer
      gain configurations that differ greatly from National Acoustic Laboratories-based
      prescriptions in quiet and in noise.

PMID- 30191770
TI  - Lupus enteritis as the sole presenting feature of systemic lupus erythematosus:
      case report and review of the literature.
AB  - Systemic lupus erythematosus (SLE) is a multisystem, autoimmune inflammatory
      disease which can affect any organ, including the gastrointestinal tract. Lupus
      enteritis is one of the manifestations of gastrointestinal involvement in SLE
      patients. However, it is exceedingly rare that lupus enteritis is the sole
      initial presentation of SLE. A 12-year-old Thai girl who had had recurrent
      abdominal pain for 2 months with no other signs of SLE on initial presentation is
      described. A single-balloon enteroscopy demonstrated segmental erythema of the
      proximal and mid-jejunum. Histopathology demonstrated active enteritis and
      submucosal vasculitis. On the basis of evidence of intestinal vasculitis,
      autoimmune profiles were performed; the results supported the possibility of SLE.
      She subsequently developed leucopenia, lymphopenia and an oral ulcer, leading to
      a robust diagnosis of SLE. Her clinical condition improved dramatically with
      prednisolone. Even though lupus enteritis is rare, it can be the initial
      presentation of SLE. In young adolescent girls with recurrent abdominal pain, the
      possibility of lupus enteritis should be borne in mind.

PMID- 30191771
TI  - Evaluation of setting time and compressive strength of a new bone cement
      precursor powder containing Mg-Na-Ca.
AB  - Taking the advantage of a novel magnesium phosphate precursor containing Na and
      Ca, the cementation rate of the cement, including only Mg/Mg-Na-Ca, was studied.
      Besides, two effective parameters, that is, calcination temperature, 650  degrees
      C and 800  degrees C, and powder-to-cement liquid ratio, 1 and 1.5 g/mL, were
      assessed. X-ray diffraction, scanning electron microscopy, ion chromatography,
      particle size analyser, Vicat needle and compression test were used to
      characterize the powders and obtained cements. The sample containing Mg-Na-Ca,
      calcined at 800  degrees C with powder-to-cement liquid ratio of 1.5, obtained
      the highest compressive strength, 20 MPa, but set fast. To control the kinetics
      of cementation, the powder containing Mg-Na-Ca calcined at 950  degrees C with
      powder-to-cement liquid ratio of 1.5 and 2 g/mL was assessed and the one with 2
      g/mL set in 9 min possessing 22 MPa compressive strength was selected as optimal
      condition to be used as a candidate, injectable bone cement.

PMID- 30191772
TI  - Antiosteoporotic Drugs to Promote Bone Regeneration Related to Titanium Implants:
      A Systematic Review and Meta-analysis.
AB  - This meta-analysis was to systematically investigate all preclinical researches
      on the possible benefits of antiosteoporotic drugs on titanium implants. Also, we
      performed a subgroup analysis to examine if the methods of drug delivery
      (systemic vs. local vs. surface coatings) or the types of antiosteoporotic drug
      (anticatabolic vs. anabolic) have more effect on bone-to-implant regeneration. A
      total of 116 articles (animal studies) were included. Poor reporting was assessed
      in the majority of the included studies. Then, results of meta-analysis showed
      that the use of osteoporotic medications significantly increased the overall
      values of micro-CT bone volume (BV) (mean differences [MD]: 21.7%, confidence
      interval [CI]: 17.8-25.7), bone-to-implant contact (BIC) (MD: 12.1%, CI: 10.6
      13.7), torque-out (MD: 5.7N.cm, CI: 4.6-6.8), and push-out (MD: 67.3N, CI: 54.6
      79.9) compared with the values of implants without osteoporotic medications.
      Also, implants coated with drugs showed higher values of BIC (MD: 16.8%, CI: 12.4
      21.3) compared with implants received drugs through systemic administration (MD:
      12.2%, CI: 10.1-14.3) or local administration (MD: 8.6%, CI: 5.8-11.4). A
      positive effect of local delivery of antiosteoporotic drugs was significant on
      push-out testing (MD: 169.8N, CI: 120.1-219.6) compared with the use of drugs
      through systemic route (MD: 51.6N, CI: 38.7-64.6) or as surface coatings (MD:
      24.1N, CI: 15.4-32.7). Finally, anabolic drugs showed a significant effect on
      push-out forces (MD: 125.5N, CI: 95.5-155.5) compared with the use of
      anticatabolic drugs (MD: 51.9N, CI: 39.5-64.5). In conclusion, the positive
      effect of antiosteoporotic drugs on osseointegration is observed in the present
      meta-analysis. Mainly, antiosteoporotic drug-coated implant surfaces showed an
      increase of BIC% compared with implants received drugs through local routes, but
      not with systemic routes. Also, the positive effect of anabolic drugs seems
      beyond the effect of anticatabolic drugs in terms of mechanical stability of
      implants as tested by push-out.

PMID- 30191773
TI  - Problems and Perspectives of Abdominal Aortic Aneurysm Research.

PMID- 30191774
TI  - Cancer Imaging, Therapy and Theranostics Based on Different Types of Functional
      Materials.

PMID- 30191775
TI  - The Therapeutic and Psychosocial Interaction in Enhancing Drug Targets.

PMID- 30191776
TI  - Brain Imaging with Positron Emission Tomography: Novel Radiopharmaceuticals.

PMID- 30191777
TI  - Alzheimer's Disease: A Review from the Pathophysiology to Diagnosis, New
      Perspectives for Pharmacological Treatment.
AB  - Dementia is characterized by the impairment of cognition and behavior of people
      over 65 years. Alzheimer's disease (AD) is the most prevalent neurodegenerative
      disorder in the world, as approximately 47 million people are affected by this
      disease and the tendency is that this number will increase to 62% by 2030. Two
      microscopic features assist in the characterization of the disease, the amyloid
      plaques and neurofibrillary agglomerates. All these factors are responsible for
      the slow and gradual deterioration of memory that affect language, personality or
      cognitive control. For the AD diagnosis, neuropsychological tests are performed
      in different spheres of cognitive functions but since not all cognitive functions
      may be affected, cerebrospinal fluid biomarkers are used along with these tests.
      To date, cholinesterase inhibitors are used as treatment, they are the only drugs
      that have shown significant improvements in the cognitive functions of AD
      patients. Despite the proven effectiveness of cholinesterase inhibitors, an AD
      carrier, even while being treated, is continually subjected to progressive
      degeneration of the neuronal tissue. For this reason, other biochemical pathways
      associated with the pathophysiology of AD have been explored as alternatives to
      the treatment of this condition such as inhibition of beta-secretase and glycogen
      synthase kinase-3beta. The present study aims to conduct a review of the
      epidemiology, pathophysiology, symptoms, diagnosis and treatment of Alzheimer's
      disease, emphasizing the research and development of new therapeutic approaches.

PMID- 30191778
TI  - Genetic and environmental contribution to the overlap between ADHD and ASD trait
      dimensions in young adults: a twin study.
AB  - BACKGROUND: Traits of attention-deficit/hyperactivity disorder (ADHD) and autism
      spectrum disorder (ASD) are strongly associated in children and adolescents,
      largely due to genetic factors. Less is known about the phenotypic and
      aetiological overlap between ADHD and ASD traits in adults. METHODS: We studied
      6866 individuals aged 20-28 years from the Swedish Study of Young Adult Twins.
      Inattention (IA) and hyperactivity/impulsivity (HI) were assessed using the WHO
      Adult ADHD Self-Report Scale-V1.1. Repetitive and restricted behaviours (RRB) and
      social interaction and communication (SIC) were assessed using the Autism-Tics,
      ADHD, and other Comorbidities inventory. We used structural equation modelling to
      decompose covariance between these ADHD and ASD trait dimensions into genetic and
      shared/non-shared environmental components. RESULTS: At the phenotypic level, IA
      was similarly correlated with RRB (r = 0.33; 95% Confidence Interval (CI) 0.31
      0.36) and with SIC (r = 0.32; 95% CI 0.29-0.34), whereas HI was more strongly
      associated with RRB (r = 0.38; 95% CI 0.35-0.40) than with SIC (r = 0.24; 95% CI
      0.21-0.26). Genetic and non-shared environmental effects accounted for similar
      proportions of the phenotypic correlations, whereas shared environmental effects
      were of minimal importance. The highest genetic correlation was between HI and
      RRB (r = 0.56; 95% 0.46-0.65), and the lowest was between HI and SIC (r = 0.33;
      95% CI 0.23-0.43). CONCLUSIONS: We found evidence for dimension-specific
      phenotypic and aetiological overlap between ADHD and ASD traits in adults. Future
      studies investigating mechanisms underlying comorbidity between ADHD and ASD may
      benefit from exploring several symptom-dimensions, rather than considering only
      broad diagnostic categories.

PMID- 30191779
TI  - Mamma Mia - A randomized controlled trial of an internet-based intervention for
      perinatal depression.
AB  - BACKGROUND: Studies suggest that 10-15% of perinatal women experience depressive
      symptoms. Due to the risks, problems with detection, and barriers to treatment,
      effective universal preventive interventions are needed. The aim of this study
      was to assess the effectiveness of an automated internet intervention ('Mamma
      Mia') on perinatal depressive symptoms. Mamma Mia is tailored specifically to the
      perinatal phase and targets risk and protective factors for perinatal depressive
      symptoms. METHODS: A total of 1342 pregnant women were randomized to an
      intervention ('Mamma Mia') and control group. Data were collected at gestational
      week (gw) 21-25, gw37, 6 weeks after birth, and 3 and 6 months after birth. We
      investigated whether (1) the intervention group displayed lower levels of
      depressive symptoms compared with the control group, (2) the effect of Mamma Mia
      changed over time, (3) the effect on depressive symptoms was moderated by
      baseline depressive symptoms, previous depression, and parity, and (4) this
      moderation changed by time. Finally, we examined if the prevalence of mothers
      with possible depression [i.e. Edinburgh Postnatal Depression Scale (EPDS)-score
      ?10] differed between the intervention and control group. RESULTS: Participants
      in the Mamma Mia group displayed less depressive symptoms than participants in
      the control group during follow-up [F(1) = 7.03, p = 0.008]. There were
      indications that the effect of Mamma Mia was moderated by EPDS score at baseline.
      The prevalence of women with EPDS-score ?10 was lower in the Mamma Mia group at
      all follow-up measurements. CONCLUSIONS: The study demonstrated the effects of
      the automated web-based universal intervention Mamma Mia on perinatal depressive
      symptoms.

PMID- 30191780
TI  - The use of thalidomide therapy for refractory epistaxis in hereditary
      haemorrhagic telangiectasia: systematic review.
AB  - BACKGROUND: Hereditary haemorrhagic telangiectasia is an autosomal dominant
      condition, characterised by mucocutaneous telangiectasia, aneurysm and
      arteriovenous malformations. Thalidomide has been used as a therapeutic strategy
      for refractory epistaxis in hereditary haemorrhagic telangiectasia patients. This
      review set out to examine the evidence for using thalidomide in the management of
      refractory epistaxis in hereditary haemorrhagic telangiectasia patients. METHODS:
      A systematic search of the available literature was performed using Medline,
      Embase, Cochrane Library and NHS Evidence databases, from inception to December
      2017. The search terms used included: hereditary haemorrhagic telangiectasia
      (HHT), Osler-Weber-Rendu syndrome, epistaxis, haemorrhage and thalidomide.
      RESULTS: All studies using thalidomide therapy showed a reduction in the
      frequency and duration of epistaxis, as early as four weeks post-therapy. In
      addition, thalidomide therapy was shown to increase median haemoglobin levels and
      reduce blood transfusion dependence. CONCLUSION: Current available evidence
      suggests that low-dose thalidomide is effective in transiently reducing epistaxis
      frequency and duration. Further studies are required to establish a treatment
      regimen to prevent side effects.

PMID- 30191781
TI  - Peroxisome proliferator-activated receptor gamma co-activator-1 alpha in
      depression and the response to electroconvulsive therapy.
AB  - BACKGROUND: The transcriptional coactivator peroxisome proliferator-activated
      receptor-gamma coactivator (PGC-1alpha), termed the 'master regulator of
      mitochondrial biogenesis', has been implicated in stress and resilience to stress
      induced depressive-like behaviours in animal models. However, there has been no
      study conducted to date to examine PGC-1alpha levels in patients with depression
      or in response to antidepressant treatment. Our aim was to assess PGC-1alpha mRNA
      levels in blood from healthy controls and patients with depression pre-/post
      electroconvulsive therapy (ECT), and to examine the relationship between blood
      PGC-1alpha mRNA levels and clinical symptoms and outcomes with ECT. METHODS:
      Whole blood PGC-1alpha mRNA levels were analysed in samples from 67 patients with
      a major depressive episode and 70 healthy controls, and in patient samples
      following a course of ECT using quantitative real-time polymerase chain reaction
      (qRT-PCR). Exploratory subgroup correlational analyses were carried out to
      determine the relationship between PGC-1alpha and mood scores. RESULTS: PGC
      1alpha levels were lower in patients with depression compared with healthy
      controls (p = 0.03). This lower level was predominantly accounted for by patients
      with psychotic unipolar depression (p = 0.004). ECT did not alter PGC-1alpha
      levels in the depressed group as a whole, though exploratory analyses revealed a
      significant increase in PGC-1alpha in patients with psychotic unipolar depression
      post-ECT (p = 0.045). We found no relationship between PGC-1alpha mRNA levels and
      depression severity or the clinical response to ECT. CONCLUSIONS: PGC-1alpha may
      represent a novel therapeutic target for the treatment of depression, and be a
      common link between various pathophysiological processes implicated in
      depression.

PMID- 30191783
TI  - The Place of Post-Traumatic Amnesia in the Assessment of Blunt Head Trauma: The
      Epistemic, Professional and Material Factors Shaping British Neurology, circa
      1920-40.
AB  - The increase in road traffic accidents in twentieth-century Britain brought with
      it a rise in the number of patients admitted to hospital with blunt, non
      penetrating head injuries. Patients who had suffered mild to moderate trauma
      typically complained of a variety of problems, including headaches, dizziness and
      giddiness. For the neurologists tasked with diagnosing and treating these
      patients, such symptoms proved difficult to assess and liable to obscure the
      clinical picture. This article focuses on why neurologists turned to time as a
      diagnostic-tool in helping to resolve these issues, specifically the measurement
      of post-traumatic amnesia (PTA). This article argues that PTA became so central
      to neurological diagnosis owing to a set of epistemic, professional and material
      factors in the decades prior to the Second World War. It concludes with a call
      for deeper appreciation of the range of issues that contribute to the shaping of
      medical theories of head trauma.

PMID- 30191784
TI  - Public Health, Social Medicine and Disease Control: Medical Services, Maternal
      Care and Sexually Transmitted Diseases in Former Portuguese West Africa (1920
      63).

PMID- 30191782
TI  - Visualising Primary Health Care: World Health Organization Representations of
      Community Health Workers, 1970-89.
AB  - For the World Health Organization (WHO), the 1978 Alma-Ata Declaration marked a
      move away from the disease-specific and technologically-focused programmes of the
      1950s and 1960s towards a reimagined strategy to provide 'Health for All by the
      Year 2000'. This new approach was centred on primary health care, a vision based
      on acceptable methods and appropriate technologies, devised in collaboration with
      communities and dependent on their full participation. Since 1948, the WHO had
      used mass communications strategies to publicise its initiatives and shape public
      attitudes, and the policy shift in the 1970s required a new visual strategy. In
      this context, community health workers (CHWs) played a central role as key visual
      identifiers of Health for All. This article examines a period of picturing and
      public information work on the part of the WHO regarding CHWs. It sets out to
      understand how the visual politics of the WHO changed to accommodate PHC as a new
      priority programme from the 1970s onwards. The argument tracks attempts to define
      CHWs and examines the techniques employed by the WHO during the 1970s and early
      1980s to promote the concept to different audiences around the world. It then
      moves to explore how the process was evaluated, as well as the difficulties in
      procuring fresh imagery. Finally, the article traces these representations
      through the 1980s, when community approaches came under sustained pressure from
      external and internal factors and imagery took on the supplementary role of
      defending the concept.

PMID- 30191785
TI  - Health Planning in 1960s Africa: International Health Organisations and the Post
      Colonial State.
AB  - This article explores the programme of national health planning carried out in
      the 1960s in West and Central Africa by the World Health Organization (WHO), in
      collaboration with the United States Agency for International Development
      (USAID). Health plans were intended as integral aspects of economic development
      planning in five newly independent countries: Gabon, Liberia, Mali, Niger and
      Sierra Leone. We begin by showing that this episode is treated only superficially
      in the existing WHO historiography, then introduce some relevant critical
      literature on the history of development planning. Next we outline the context
      for health planning, noting: the opportunities which independence from colonial
      control offered to international development agencies; the WHO's limited capacity
      in Africa; and its preliminary efforts to avoid imposing Western values or
      partisan views of health system organisation. Our analysis of the plans
      themselves suggests they lacked the necessary administrative and statistical
      capacity properly to gauge local needs, while the absence of significant
      financial resources meant that they proposed little more than augmentation of
      existing structures. By the late 1960s optimism gave way to disappointment as it
      became apparent that implementation had been minimal. We describe the ensuing
      conflict within WHO over programme evaluation and ongoing expenditure, which
      exposed differences of opinion between African and American officials over
      approaches to international health aid. We conclude with a discussion of how the
      plans set in train longer processes of development planning, and, perhaps less
      desirably, gave bureaucratic shape to the post-colonial state.

PMID- 30191786
TI  - 'Tolerable Intolerance': Protestantism, Sectarianism and Voluntary Hospitals in
      Late-nineteenth-century London.
AB  - This article interrogates the complicated understanding of sectarianism in
      institutional cultures in late-nineteenth-century England through an examination
      of the practice of religion in the daily life of hospital wards in voluntary
      hospitals. Voluntary hospitals prided themselves on their identity as
      philanthropic institutions free from sectarian practices. The public accusation
      of sectarianism against University College Hospital triggered a series of
      responses that suggests that hospital practices reflected and reinforced an
      acceptable degree of 'tolerable intolerance'. The debates this incident prompted
      help us to interrogate the meaning of sectarianism in late nineteenth-century
      England. How was sectarianism understood? Why was it so important for voluntary
      institutions to appear free from sectarian influences? How did the responses to
      claims of sectarian attitudes influence the actions of the male governors,
      administrators and medical staff of voluntary hospitals? The contradictory
      meanings of sectarianism are examined in three interrelated themes: the patient,
      daily life on the wards and hospital funding. The broader debates that arose from
      the threat of 'sectarianism in hospital' uncovers the extent to which religious
      practices were ingrained in hospital spaces throughout England and remained so
      long afterwards. Despite the increasing medicalisation and secularisation of
      hospital spaces, religious practices and symbols were embedded in the daily life
      of voluntary hospitals.

PMID- 30191799
TI  - MDH volume 62 Issue 4 Cover and Front matter.

PMID- 30191801
TI  - MDH volume 62 Issue 4 Cover and Back matter.

PMID- 30191800
TI  - Medicamenta: A Virtual Exhibition with Stories of Diseases and Remedies in
      Antique Books at the University of Padua (Italy).

PMID- 30191802
TI  - Molecular Epidemiology, Ecology, and Evolution of Group A Streptococci.
AB  - The clinico-epidemiological features of diseases caused by group A streptococci
      (GAS) is presented through the lens of the ecology, population genetics, and
      evolution of the organism. The serological targets of three typing schemes (M, T,
      SOF) are themselves GAS cell surface proteins that have a myriad of virulence
      functions and a diverse array of structural forms. Horizontal gene transfer
      expands the GAS antigenic cell surface repertoire by generating numerous
      combinations of M, T, and SOF antigens. However, horizontal gene transfer of the
      serotype determinant genes is not unconstrained, and therein lies a genetic
      organization that may signify adaptations to a narrow ecological niche, such as
      the primary tissue reservoirs of the human host. Adaptations may be further
      shaped by selection pressures such as herd immunity. Understanding the molecular
      evolution of GAS on multiple levels-short, intermediate, and long term-sheds
      insight on mechanisms of host-pathogen interactions, the emergence and spread of
      new clones, rational vaccine design, and public health interventions.

PMID- 30191803
TI  - Processive Antitermination.
AB  - Transcription is a discontinuous process, where each nucleotide incorporation
      cycle offers a decision between elongation, pausing, halting, or termination.
      Many cis-acting regulatory RNAs, such as riboswitches, exert their influence over
      transcription elongation. Through such mechanisms, certain RNA elements can
      couple physiological or environmental signals to transcription attenuation, a
      process where cis-acting regulatory RNAs directly influence formation of
      transcription termination signals. However, through another regulatory mechanism
      called processive antitermination (PA), RNA polymerase can bypass termination
      sites over much greater distances than transcription attenuation. PA mechanisms
      are widespread in bacteria, although only a few classes have been discovered
      overall. Also, although traditional, signal-responsive riboswitches have not yet
      been discovered to promote PA, it is increasingly clear that small RNA elements
      are still oftentimes required. In some instances, small RNA elements serve as
      loading sites for cellular factors that promote PA. In other instances, larger,
      more complicated RNA elements participate in PA in unknown ways, perhaps even
      acting alone to trigger PA activity. These discoveries suggest that what is now
      needed is a systematic exploration of PA in bacteria, to determine how broadly
      these transcription elongation mechanisms are utilized, to reveal the diversity
      in their molecular mechanisms, and to understand the general logic behind their
      cellular applications. This review covers the known examples of PA regulatory
      mechanisms and speculates that they may be broadly important to bacteria.

PMID- 30191805
TI  - Transmission Surveillance for Antimicrobial-Resistant Organisms in the Health
      System.
AB  - Surveillance of antibiotic resistance involves the collection of antibiotic
      susceptibility patterns undertaken by clinical microbiology laboratories on
      bacteria isolated from clinical specimens. Global surveillance programs have
      shown that antibiotic resistance is a major threat to the public at large and
      play a crucial role in the development of enhanced diagnostics as well as
      potential vaccines and novel antibiotics with activity against antimicrobial
      resistant organisms. This review focuses primarily on examples of global
      surveillance systems. Local, national, and global integrated surveillance
      programs with sufficient data linkage between these schemes, accompanied by
      enhanced genomics and user-friendly bioinformatics systems, promise to overcome
      some of the stumbling blocks encountered in the understanding, emergence, and
      transmission of antimicrobial-resistant organisms.

PMID- 30191806
TI  - Causality in Biological Transmission: Forces and Energies.
AB  - Transmission is a basic process in biology that can be analyzed in accordance
      with information theory. A sender or transmitter located in a particular patch of
      space is the source of the transmitted object, the message. A receiver patch
      interacts to receive the message. The "messages" that are transmitted between
      patches (eventually located in different hierarchical biological levels) are
      "meaningful" biological entities (biosemiotics). cis-acting transmission occurs
      when unenclosed patches acting as emitter and receiver entities of the same
      hierarchical level are linked (frequently by a vehicle) across an unfit space;
      trans-acting transmission occurs between biological individuals of different
      hierarchical levels, embedded within a close external common limit. To understand
      the causal frame of transmission events, we analyze the ultimate, but most
      importantly also the proximate, causes of transmission. These include the
      repelling, centrifugal "forces" influencing the transmission (emigration) and the
      attractive, centripetal "energies" involved in the reception (immigration). As
      transmission is a key process in evolution, creating both genetic-embedded
      complexity-diversity (trans-acting transmission, as introgression), and exposure
      to novel and alternative patches-environments (cis-acting transmission, as
      migration), the causal frame of transmission shows the cis-evolutionary and trans
      evolutionary dimensions of evolution.

PMID- 30191808
TI  - PCD Advances Recommendations From First-Ever External Review.

PMID- 30191804
TI  - RNA Localization in Bacteria.
AB  - Diverse mechanisms and functions of posttranscriptional regulation by small
      regulatory RNAs and RNA-binding proteins have been described in bacteria. In
      contrast, little is known about the spatial organization of RNAs in bacterial
      cells. In eukaryotes, subcellular localization and transport of RNAs play
      important roles in diverse physiological processes, such as embryonic patterning,
      asymmetric cell division, epithelial polarity, and neuronal plasticity. It is now
      clear that bacterial RNAs also can accumulate at distinct sites in the cell.
      However, due to the small size of bacterial cells, RNA localization and
      localization-associated functions are more challenging to study in bacterial
      cells, and the underlying molecular mechanisms of transcript localization are
      less understood. Here, we review the emerging examples of RNAs localized to
      specific subcellular locations in bacteria, with indications that subcellular
      localization of transcripts might be important for gene expression and regulatory
      processes. Diverse mechanisms for bacterial RNA localization have been suggested,
      including close association to their genomic site of transcription, or to the
      localizations of their protein products in translation-dependent or -independent
      processes. We also provide an overview of the state of the art of technologies to
      visualize and track bacterial RNAs, ranging from hybridization-based approaches
      in fixed cells to in vivo imaging approaches using fluorescent protein reporters
      and/or RNA aptamers in single living bacterial cells. We conclude with a
      discussion of open questions in the field and ongoing technological developments
      regarding RNA imaging in eukaryotic systems that might likewise provide novel
      insights into RNA localization in bacteria.

PMID- 30191807
TI  - Dual-Function RNAs.
AB  - Bacteria are known to use RNA, either as mRNAs encoding proteins or as noncoding
      small RNAs (sRNAs), to regulate numerous biological processes. However, a few
      sRNAs have two functions: they act as base-pairing RNAs and encode a small
      protein with additional regulatory functions. Thus, these so called "dual
      function" sRNAs can serve as both a riboregulator and an mRNA. In some cases,
      these two functions can act independently within the same pathway, while in other
      cases, the base-pairing function and protein function act in different pathways.
      Here, we discuss the five known dual-function sRNAs-SgrS from enteric species,
      RNAIII and Psm-mec from Staphylococcus aureus, Pel RNA from Streptococcus
      pyogenes, and SR1 from Bacillus subtilis-and review their mechanisms of action
      and roles in regulating diverse biological processes. We also discuss the
      prospect of finding additional dual-function sRNAs and future challenges in
      studying the overlap and competition between the functions.

PMID- 30191809
TI  - Medicaid Coverage of Guidelines-Based Asthma Care Across 50 States, the District
      of Columbia, and Puerto Rico, 2016-2017.
AB  - Asthma affects more than 24 million Americans, including 6.2 million children.
      Although asthma cannot be cured, it can be effectively managed with care based on
      nationally recognized guidelines. Ensuring the availability and accessibility of
      guidelines-recommended treatments and services can help patients receive the most
      appropriate care. In this article, we describe the American Lung Association's
      Asthma Guidelines-Based Care Coverage Project (the Project) to determine the
      extent of asthma care coverage and associated barriers in state Medicaid programs
      - information that has been previously unavailable. The Project tracked coverage
      for 7 areas of guidelines-based asthma care and 9 barriers related to accessing
      care in Medicaid programs for all 50 states, the District of Columbia, and Puerto
      Rico. Results from the Project show a lack of consistent and comprehensive
      coverage across states, as well as coverage-related challenges to accessing
      asthma care within states.

PMID- 30191810
TI  - Availability of the National Diabetes Prevention Program in United States
      Counties, March 2017.

PMID- 30191811
TI  - Acute polyradiculopathy secondary to idelalisib in Relapsed Classical Hodgkin's
      lymphoma.
AB  - Patients with relapsed or refractory Hodgkin's lymphoma are likely incurable with
      standard treatment. Idelalisib, a delta-isoform specific Phosphatidyl-inositol-3
      kinase (PI3K) inhibitor has shown its efficacy in other hematopoietic B
      malignancies. We report the case of a 51-years old patient with relapsed and
      refractory Hodgkin's Lymphoma receiving idelalisib after several regimens of
      chemotherapy. He achieved a good partial response for several months,
      unfortunately, idelalisib had to be stopped because of the onset of a severe
      polyradiculoneuritis attributed to this treatment. We assume here that the
      polyradiculoneuritis could be caused by T cell mediated autoimmunity to myelin
      proteins. To our knowledge, this adverse event has never been described so far
      with idelalisib.

PMID- 30191812
TI  - Measles, war, and health-care reforms in Ukraine.

PMID- 30191813
TI  - Does a spoonful of honey make the medicine go down?

PMID- 30191814
TI  - A surrender to dirty energy.

PMID- 30191815
TI  - Ending HIV epidemics among people who inject drugs in LMICs.

PMID- 30191816
TI  - Improving observational studies in the era of big data.

PMID- 30191817
TI  - Pneumonia: a global cause without champions.

PMID- 30191818
TI  - Offline: Frantz Fanon and the origins of global health.

PMID- 30191819
TI  - Health in the UK in a no-deal Brexit.

PMID- 30191820
TI  - Prospects for US single-payer national health care.

PMID- 30191821
TI  - 41 000 measles cases in Europe since the beginning of 2018.

PMID- 30191822
TI  - Ulana Suprun: the accidental reformer.

PMID- 30191823
TI  - CDC autism rate: misplaced reliance on passive sampling?

PMID- 30191824
TI  - Women's work in UK clinical trials is undervalued.

PMID- 30191825
TI  - Sirolimus for systemic lupus erythematosus.

PMID- 30191826
TI  - Sirolimus for systemic lupus erythematosus - Authors' reply.

PMID- 30191827
TI  - GBD 2016 estimates problematic for South Africa.

PMID- 30191828
TI  - Evidence-based psychological therapies for insomnia.

PMID- 30191829
TI  - Young Frankenstein and The Lancet.

PMID- 30191831
TI  - An ominous sign from Sister Mary Joseph.

PMID- 30191833
TI  - Red light on Chengdu air pollution.

PMID- 30191830
TI  - A scalable, integrated intervention to engage people who inject drugs in HIV care
      and medication-assisted treatment (HPTN 074): a randomised, controlled phase 3
      feasibility and efficacy study.
AB  - BACKGROUND: People who inject drugs (PWID) have a high incidence of HIV, little
      access to antiretroviral therapy (ART) and medication-assisted treatment (MAT),
      and high mortality. We aimed to assess the feasibility of a future controlled
      trial based on the incidence of HIV, enrolment, retention, and uptake of the
      intervention, and the efficacy of an integrated and flexible intervention on ART
      use, viral suppression, and MAT use. METHODS: This randomised, controlled
      vanguard study was run in Kyiv, Ukraine (one community site), Thai Nguyen,
      Vietnam (two district health centre sites), and Jakarta, Indonesia (one hospital
      site). PWID who were HIV infected (index participants) and non-infected injection
      partners were recruited as PWID network units and were eligible for screening if
      they were aged 18-45 years (updated to 18-60 years 8 months into study), and
      active injection drug users. Further eligibility criteria for index participants
      included a viral load of 1000 copies per mL or higher, willingness and ability to
      recruit at least one injection partner who would be willing to participate. Index
      participants were randomly assigned via a computer generated sequence accessed
      through a secure web portal (3:1) to standard of care or intervention, stratified
      by site. Masking of assignment was not possible due to the nature of
      intervention. The intervention comprised systems navigation, psychosocial
      counselling, and ART at any CD4 count. Local ART and MAT services were used.
      Participants were followed up for 12-24 months. The primary objective was to
      assess the feasibility of a future randomised controlled trial. To achieve this
      aim we looked at the following endpoints: HIV incidence among injection partners
      in the standard of care group, and enrolment and retention of HIV-infected PWID
      and their injection partners and the uptake of the integrated intervention. The
      study was also designed to assess the feasibility, barriers, and uptake of the
      integrated intervention. Endpoints were assessed in a modified intention-to-treat
      popualtion after exclusion of ineligible participants. This trial is registered
      on ClinicalTrials.gov, NCT02935296, and is active but not recruiting new
      participants. FINDINGS: Between Feb 5, 2015, and June 3, 2016, 3343 potential
      index participants were screened, of whom 502 (15%) were eligible and enrolled.
      1171 injection partners were referred, and 806 (69%) were eligible and enrolled.
      Index participants were randomly assigned to intervention (126 [25%]) and
      standard of care (376 [75%]) groups. At week 52, most living index participants
      (389 [86%] of 451) and partners (567 [80%] of 710) were retained, and self
      reported ART use was higher among index participants in the intervention group
      than those in the standard of care group (probability ratio [PR] 1.7, 95% CI 1.4
      1.9). Viral suppression was also higher in the intervention group than in the
      standard of care group (PR 1.7, 95% CI 1.3-2.2). Index participants in the
      intervention group reported more MAT use at 52 weeks than those in the standard
      of care group (PR 1.7, 95% CI 1.3-2.2). Seven incident HIV infections occurred,
      and all in injection partners in the standard of care group (intervention
      incidence 0.0 per 100 person-years, 95% CI 0.0-1.7; standard of care incidence
      1.0 per 100 person-years, 95% CI 0.4-2.1; incidence rate difference -1.0 per 100
      person-years, 95% CI -2.1 to 1.1). No severe adverse events due to the
      intervention were recorded. INTERPRETATION: This vanguard study provides evidence
      that a flexible, scalable intervention increases ART and MAT use and reduces
      mortality among PWID. The low incidence of HIV in both groups impedes a future
      randomised, controlled trial, but given the strength of the effect of the
      intervention, its implementation among HIV-infected PWID should be considered.
      FUNDING: US National Institutes of Health.

PMID- 30191832
TI  - Time to act on injectable-free regimens for children with multidrug-resistant
      tuberculosis.

PMID- 30191834
TI  - Corrections.

PMID- 30191835
TI  - Oncology, "fake" news, and legal liability.

PMID- 30191836
TI  - Choice of control group in randomised trials of cancer medicine: are we testing
      trivialities?

PMID- 30191837
TI  - A new model for training in hybrid imaging.

PMID- 30191838
TI  - Meeting junior oncologists where they are: on their phones.

PMID- 30191839
TI  - A physician's hand tumour induced by the first X-ray procedures.

PMID- 30191840
TI  - Oesophageal preservation in locally advanced oesophageal cancer.

PMID- 30191841
TI  - Oesophageal preservation in locally advanced oesophageal cancer - Authors' reply.

PMID- 30191843
TI  - Exercise as part of routine cancer care.

PMID- 30191842
TI  - Exercise as part of routine cancer care.

PMID- 30191844
TI  - Is combining PARP and androgen receptor inhibition really a winning strategy in
      metastatic castration-resistant prostate cancer?

PMID- 30191845
TI  - Is combining PARP and androgen receptor inhibition really a winning strategy in
      metastatic castration-resistant prostate cancer? - Authors' reply.

PMID- 30191846
TI  - Targeted therapy: a potential oversight in trial protocol.

PMID- 30191847
TI  - Correction to Lancet Oncol 2018; 19: 1239-46.

PMID- 30191848
TI  - Correction to Lancet Oncol 2018; 19: 940-52.

PMID- 30191849
TI  - Immune checkpoint inhibitors and cardiovascular toxicity.
AB  - Immune checkpoint inhibitors are a new class of anticancer therapies that amplify
      T-cell-mediated immune responses against cancer cells. Immune checkpoint
      inhibitors have shown important benefits in phase 3 trials, and several agents
      have been approved for specific malignancies. Although adverse events from immune
      checkpoint inhibitors are a common occurrence, cardiotoxic effects are uncommon,
      but are often serious complications with a relatively high mortality. Most
      cardiotoxic effects appear to be inflammatory in nature. Clinical assessment of a
      combination of biomarkers, electrocardiography, cardiac imaging, and
      endomyocardial biopsy can be used to confirm a possible diagnosis. In this
      Review, we discuss the epidemiology of immune checkpoint inhibitor-mediated
      cardiotoxic effects, as well as their clinical presentation, subtypes, risk
      factors, pathophysiology, and clinical management, including the introduction of
      a new surveillance strategy.

PMID- 30191851
TI  - Will liquid biopsies improve outcomes for patients with small-cell lung cancer?
AB  - Small-cell lung cancer (SCLC) is an aggressive tumour that seeds metastases early
      with dismal outcomes. As expected from a disease that is closely associated with
      smoking, mutation burden in SCLC is high. Intratumoral and intertumoral
      heterogeneity is a substantial obstacle to successful treatment and the SCLC
      genomic landscape reveals few targets that are readily druggable. Chemotherapy
      elicits responses in most patients with SCLC, but their effects are short lived.
      Multiple clinical trials have been unsuccessful in showing positive survival
      outcomes and biomarkers to select patients and monitor responses to novel
      targeted treatments have been lacking, not least because acquisition of tumour
      biopsies, especially during relapse after chemotherapy, is a substantial
      challenge. Liquid biopsies via blood sampling in SCLC, notably circulating tumour
      cells and circulating free tumour DNA can be readily and repeatedly accessed, and
      are beginning to yield promising data to inform SCLC biology and patient
      treatment. Primary cell cultures and preclinical mouse models can also be derived
      from the relatively plentiful SCLC circulating tumour cells providing a tractable
      platform for SCLC translational research and drug development.

PMID- 30191850
TI  - Statistical analysis of patient-reported outcome data in randomised controlled
      trials of locally advanced and metastatic breast cancer: a systematic review.
AB  - Although patient-reported outcomes (PROs), such as health-related quality of
      life, are important endpoints in randomised controlled trials (RCTs), there is
      little consensus about the analysis, interpretation, and reporting of these data.
      We did a systematic review to assess the variability, quality, and standards of
      PRO data analyses in advanced breast cancer RCTs. We searched PubMed for English
      language articles published in peer-reviewed journals between Jan 1, 2001, and
      Oct 30, 2017. Eligible articles were those that reported PRO results from RCTs of
      adult patients with advanced breast cancer receiving anti-cancer treatments with
      reported sample sizes of at least 50 patients-66 RCTs met the selection criteria.
      Only eight (12%) RCTs reported a specific PRO research hypothesis. Heterogeneity
      in the statistical methods used to assess PRO data was observed, with a mixture
      of longitudinal and cross-sectional techniques. Not all articles addressed the
      problem of multiple testing. Fewer than half of RCTs (28 [42%]) reported the
      clinical significance of their findings. 48 (73%) did not report how missing data
      were handled. Our systematic review shows a need to improve standards in the
      analysis, interpretation, and reporting of PRO data in cancer RCTs. Lack of
      standardisation makes it difficult to draw robust conclusions and compare
      findings across trials. The Setting International Standards in the Analyzing
      Patient-Reported Outcomes and Quality of Life Data Consortium was set up to
      address this need and develop recommendations on the analysis of PRO data in
      RCTs.

PMID- 30191852
TI  - The effect of natural disasters on cancer care: a systematic review.
AB  - As the incidence of cancer and the frequency of extreme weather events rise,
      disaster mitigation is becoming increasingly relevant to oncology care. In this
      systematic Review, we aimed to investigate the effect of natural disasters on
      cancer care and the associated health effects on patients with cancer. We
      searched MEDLINE, Embase, Scopus, CINAHL, PsycINFO, Web of Science, and
      ScienceDirect for articles published between database inception and November 12,
      2016. Articles identifying the effect of natural disasters on oncology services
      or the associated health implications for patients with cancer were included.
      Only articles published in English were included. Data extraction was done by two
      authors independently and then verified by all authors. The effects of disaster
      events on oncology services, survival outcomes, and psychological issues were
      assessed. Of the 4593 studies identified, only 85 articles met all the
      eligibility criteria. Damage to infrastructure, communication systems and
      medication, and medical record losses substantially disrupt oncology care. The
      effect of extreme weather events on survival outcomes is limited to only a small
      number of studies, often with inadequate follow-up periods. Natural disasters
      cause substantial interruption to the provision of oncology care. To the best of
      our knowledge, this is the first systematic Review to assess the existing
      evidence base on the health effects of natural disaster events on cancer care. We
      advocate for the consideration of patients with cancer during disaster planning.

PMID- 30191853
TI  - Blistering Langerhans cell histiocytosis.

PMID- 30191854
TI  - Gastrointestinal Cancers-Carving Out the Optimal Local Therapies in the
      Gastrointestinal Tract.

PMID- 30191855
TI  - Radiation Safety and Cardiovascular Implantable Electronic Devices.

PMID- 30191856
TI  - The Future of Artificial Intelligence in Radiation Oncology.

PMID- 30191857
TI  - Update on Requirements for Medical Dosimetry Certification in the United States.

PMID- 30191858
TI  - Physician Leadership Development: A Pilot Program for Radiation Oncology
      Residents.

PMID- 30191860
TI  - To Treat or Not to Treat? A Postmastectomy Question.

PMID- 30191859
TI  - Simulation as More Than a Treatment-Planning Tool: A Systematic Review of the
      Literature on Radiation Oncology Simulation-Based Medical Education.
AB  - PURPOSE: Simulation-based medical education (SBME) is gaining prominence as a
      tool to meet Accreditation Council for Graduate Medical Education-mandated
      competency-based assessment educational goals. SBME is used in radiation
      oncology, although the type and extent are not clear. This study reports a
      systematic literature review designed to clarify the type and extent of radiation
      oncology SBME. METHODS AND MATERIALS: The systematic review focused on radiation
      oncology SBME literature. The methods followed Preferred Reporting Items for
      Systematic Reviews and Meta-Analyses guidelines. The inclusion criteria were
      identified according to the PICOS (population, intervention, comparison, outcome,
      and setting) framework. The population included undergraduate, graduate, and
      continuing medical education learners. Studies were limited to English-language
      studies published on or after January 1, 1990, in peer-reviewed journals. PubMed,
      MedEdPORTAL, and in-press articles were searched. The PubMed search was conducted
      using predefined search terms. References and similar articles were examined.
      Medical Subject Headings terms in selected articles were reviewed to ensure
      relevant terms were included. RESULTS: Fifty-four SBME publications met the
      inclusion criteria. Only 9 of 54 studies (17%) self-identified as SBME. SBME
      types included screen-based simulators (56%), simulated environments (13%),
      virtual reality and haptic systems (13%), simulated patients (11%), part-task
      trainers (6%), and computer-based systems with mannequins (2%). A variety of
      radiation oncology skill sets were addressed, including contouring (54%),
      treatment planning (20%), clinical decision making (17%), anatomy and/or
      radiology (13%), radiation biology and/or physics (13%), communication skills
      and/or patient education (13%), brachytherapy (13%), and immobilization (11%). A
      target learning population was defined in 47 studies, including residents (53%),
      attending physicians (36%), medical students (21%), medical physicists (11%),
      radiation therapists (9%), nurses (6%), administrative staff (4%), and
      dosimetrists (4%). Learner feedback was reported in 32 studies. CONCLUSIONS:
      Overall, this systematic literature review provides context and guidance for
      future radiation oncology SBME development. Appropriately framing SBME reports in
      the radiation oncology literature will facilitate development, implementation,
      and evaluation of SBME interventions. SBME resources should be centralized to
      facilitate dissemination and share resources.

PMID- 30191861
TI  - Post-mastectomy Radiation Yes but Internal Mammary Nodes No.

PMID- 30191862
TI  - Radiation but With Delayed Reconstruction.

PMID- 30191863
TI  - Post-mastectomy Radiation, All in.

PMID- 30191864
TI  - Multicenter Trial of Stereotactic Body Radiation Therapy for Low- and
      Intermediate-Risk Prostate Cancer: Survival and Toxicity Endpoints.
AB  - PURPOSE: The radiobiology of prostate cancer may favor the extreme
      hypofractionation inherent in stereotactic body radiation therapy (SBRT);
      however, data from a large multicenter study are lacking. We therefore examined
      the hypothesis that dose-escalated SBRT can be safely administered across
      multiple institutions, with favorable 5-year disease-free survival (DFS) rates
      compared with historical controls. METHODS AND MATERIALS: Twenty-one centers
      enrolled 309 patients with prostate adenocarcinoma: 172 with low-risk (LR) and
      137 with intermediate-risk (IR) disease. All were treated with a non-coplanar
      robotic SBRT platform using real-time tracking of implanted fiducials. The
      prostate was prescribed 40 Gy in 5 fractions of 8 Gy. We assessed toxicities
      using Common Terminology Criteria for Adverse Events (CTCAE) version 3 and
      biochemical failure using the "nadir + 2" definition. The study population
      yielded 90% power to identify excessive (>10%) rates of grade >=3 genitourinary
      (GU) or gastrointestinal toxicities and, in the LR group, 80% power to show
      superiority in DFS over a 93% historical comparison rate. RESULTS: At a median
      follow-up of 61 months, 2 LR patients (1.2%) and 2 IR patients (1.5%) experienced
      grade 3 GU toxicities, far below the 10% toxicity rate deemed excessive (upper
      limits of 95% confidence interval, 3.5% and 4.3%, respectively). No grade 4 or 5
      toxicities occurred. All grade 3 toxicities were GU, occurring 11 to 51 months
      after treatment. For the entire group, the actuarial 5-year overall survival rate
      was 95.6% and the DFS rate was 97.1%. The 5-year DFS rate was 97.3% for LR
      patients (superior to the 93% DFS rate for historical controls; P = .0008; lower
      limit of 95% confidence interval, 94.6%) and 97.1% for IR patients. CONCLUSIONS:
      Dose-escalated prostate SBRT was administered with minimal toxicity in this multi
      institutional study. Relapse rates compared favorably with historical controls.
      SBRT is a suitable option for LR and IR prostate cancer.

PMID- 30191865
TI  - Use of Radiation in Extramedullary Leukemia/Chloroma: Guidelines From the
      International Lymphoma Radiation Oncology Group.
AB  - Survival times for patients with leukemia generally have improved in recent
      decades, and this improvement has been attributed to an enhanced understanding of
      the genetics driving the cause of the disease and improved combinations of
      chemotherapy and targeted therapy. Durable control of systemic disease in blood
      and bone marrow has significantly improved survival, but extramedullary relapse
      can pose therapeutic challenges for which radiation therapy can have an important
      role. This report discusses the current role of radiation therapy for patients
      with leukemia, specifically the extramedullary manifestations of leukemia.

PMID- 30191866
TI  - Choosing Wisely at the End of Life: Use of Shorter Courses of Palliative
      Radiation Therapy for Bone Metastasis.
AB  - PURPOSE: American Society for Radiation Choosing Wisely guidelines recommend <=10
      fractions of radiation therapy (RT) for bone metastasis, with consideration for 1
      fraction in patients with a poor prognosis. The purpose of this analysis was to
      evaluate characteristic differences in guideline concordance to fractionation
      regimens in a modern cohort of older patients with a diagnosis of bone
      metastasis. METHODS AND MATERIALS: Medicare beneficiaries aged >=65 years treated
      with RT for bone metastasis from 2012 to 2015 were identified. Guideline
      concordant RT fractionation was defined in the entire cohort as <=10 fractions.
      Utilization of 1 fraction versus >=2 fractions was analyzed in deceased patients.
      Patient demographic, disease, and facility characteristics associated with
      shorter fractionation were analyzed. RESULTS: In 569 patients treated with RT,
      the median age at diagnosis was 73 years. The most common cancer types were lung
      (37%), genitourinary (26%), breast (15%), and gastrointestinal (10%). Among all
      patients, 34%, 30%, and 36% received 1 fraction, 2 to 10 fractions, and >=11
      fractions, respectively. In comparison with receipt of 1 to 10 fractions, receipt
      of >=11 fractions was associated with a $1467 increase in per-patient cost to
      Medicare during the calendar quarter of RT. Almost two-thirds of patients who
      died within 30 days of RT completion were treated with >1 fraction. CONCLUSIONS:
      Although guideline concordance was high overall, a large number of patients
      received longer courses of RT at the end of life. Strong consideration should be
      made for utilization of shorter courses, particularly in patients with a limited
      prognosis.

PMID- 30191867
TI  - Effect of Patient Immune Status on the Efficacy of Radiation Therapy and
      Recurrence-Free Survival Among 805 Patients With Merkel Cell Carcinoma.
AB  - PURPOSE: Patients with Merkel cell carcinoma (MCC) with chronic immunosuppression
      (IS) have worse outcomes, but the mechanisms are not well understood. We
      hypothesized that these differences may be mediated in part by differential
      response to treatment, and we evaluated whether radiation therapy (RT) efficacy
      is altered among IS compared with immune-competent (IC) patients with MCC.
      METHODS AND MATERIALS: Among 805 patients with MCC, recurrence-free survival
      (RFS) and patterns of first recurrence were compared between 89 IS and 716 IC
      patients with stage I to III MCC treated with curative intent. We used a Fine and
      Gray's competing risk multivariable analysis to estimate associations with RFS.
      RESULTS: IS and IC patients with MCC had similar demographic and disease
      characteristics. Most (77% IC, 86% IS) were irradiated (median, 50.4 Gy IC, 50.3
      Gy IS), although more IS patients were irradiated to the primary site (97% vs
      81%). With a median follow-up of 54.4 months, IS patients had inferior RFS (2
      year: 30% vs 57%; P < .0001) and higher rates of local recurrence as the first
      site of relapse (25% vs 12%; P = .0002). The association between RT and RFS
      differed by immune status (interaction P = .01). Although RT was associated with
      significantly improved RFS among IC patients (hazard ratio 0.56, 95% confidence
      interval 0.44-0.72), no difference in RFS was observed with RT among IS patients
      (hazard ratio 1.49, 95% confidence interval 0.70-3.17). CONCLUSIONS: Radiation
      therapy efficacy at current standard RT doses for MCC is impaired among
      immunosuppressed patients with MCC. Although a strong link between durability of
      RT response and immune function does not appear to be evident in most cancers,
      our results may reflect an especially dynamic interaction between immune status
      and RT efficacy in MCC.

PMID- 30191868
TI  - Long-Term Late Toxicity, Quality of Life, and Emotional Distress in Patients With
      Nasopharyngeal Carcinoma Treated With Intensity Modulated Radiation Therapy.
AB  - PURPOSE: To report long-term (>4 years) toxicity and quality of life (QoL) among
      patients with nasopharyngeal carcinoma (NPC) treated with intensity modulated
      radiation therapy (IMRT) in a nonendemic center. METHODS AND MATERIALS: A cross
      sectional cohort study enrolled patients with NPC who were disease-free and >=4
      years after IMRT +/- chemotherapy. Physician-reported adverse events (Common
      Terminology Criteria for Adverse Events, version 4.03) and patient-reported QoL
      (Functional Assessment of Cancer Therapy-Head and Neck, Functional Assessment of
      Chronic Illness Therapy-Fatigue), utilities (EuroQOL-5D), head and neck symptoms
      (MD Anderson Symptom Inventory-Head and Neck), and emotional distress (Hospital
      Anxiety and Depression Scale) were collected. Consenting patients also underwent
      endocrine screening and audiometry. RESULTS: Among 107 patients enrolled, median
      age at enrollment and time since treatment were 57 (32-81) and 7.5 years (4.2
      11.1), respectively. Most patients (99%) received 70 Gy in 35 fractions; the
      majority (93%) received concurrent chemotherapy. Mean scores for the Functional
      Assessment of Cancer Therapy-Head and Neck, Functional Assessment of Chronic
      Illness Therapy-Fatigue, and EuroQOL-5D were 105.0 (46-148), 116.6 (44-160), and
      0.85 (0.29-1.00), respectively. Dry mouth, mucus, swallowing/chewing, memory, and
      teeth/gum problems were scored highest on the MD Anderson Symptom Inventory-Head
      and Neck; mean symptom severity and symptom interference scores were 2.3 and 2.4,
      respectively. Grade 3 or higher physician-reported adverse events were noted in
      50 patients (47%), most frequently hearing problems (46, 43%). Audiometry
      revealed significant bilateral hearing loss (grade >=3) in 68 patients (72%).
      Depression (25%), anxiety (37%), and fatigue (28%) were common and strongly
      correlated with QoL. Most patients (69%) developed hypothyroidism; 1 patient (1%)
      developed pituitary dysfunction requiring hormone replacement. V50 >90 and V45
      >99 to the thyroid correlated with significantly higher rates of hypothyroidism.
      CONCLUSIONS: Despite the implementation of IMRT, survivors of NPC still
      experience many physical symptoms that affect long-term QoL many years after
      treatment. Depression, anxiety, and fatigue remain common in long-term survivors
      and are highly correlated with QoL.

PMID- 30191869
TI  - Definitive Carbon-Ion Radiation Therapy for Locally Advanced Sinonasal Malignant
      Tumors: Subgroup Analysis of a Multicenter Study by the Japan Carbon-Ion
      Radiation Oncology Study Group (J-CROS).
AB  - PURPOSE: To evaluate the safety and efficacy of carbon-ion radiation therapy (C
      ion RT) for locally advanced sinonasal malignant tumors in a multicenter
      retrospective study (J-CROS 1402 HN). METHODS AND MATERIALS: Clinical data were
      collected for patients who had sinonasal malignant tumors of stage N0-1M0 and
      received C-ion RT at 4 institutions in Japan between November 2003 and December
      2014. Of the 458 patients, 393 had naive tumors and 65 had recurrent tumors. The
      tumors were located in the nasal cavity (n = 263), maxillary sinus (n = 109),
      ethmoid sinus (n = 71), and other locations (n = 15). The histologic types were
      mucosal melanoma (n = 221, 48%), adenoid cystic carcinoma (n = 122, 27%),
      squamous cell carcinoma (n = 31, 7%), olfactory neuroblastoma (n = 30, 7%),
      adenocarcinoma (n = 21, 5%), and other types (n = 33, 7%). Of the 458 patients,
      300 (66%) had T4 tumors. All patients received definitive C-ion RT. RESULTS: The
      median follow-up period was 25.2 months for all patients (range, 1.4-132.3
      months). The 2-year overall survival and local control rates were 79.6% and
      84.1%, respectively. As analyzed according to histology, the 2-year overall
      survival rate was 68.0% for mucosal melanoma, 96.8% for adenoid cystic carcinoma,
      70.0% for squamous cell carcinoma, 96.7% for olfactory neuroblastoma, and 89.7%
      for adenocarcinoma. Regarding late toxicities, 17% of patients developed grade 3
      and 4 toxicities, of which visual impairment was the most common. CONCLUSION: The
      results of our multicenter study have demonstrated that C-ion RT can provide
      excellent clinical outcomes with acceptable late toxicities in patients who have
      locally advanced sinonasal malignant tumors.

PMID- 30191870
TI  - Radiation Therapy Is Associated With an Increased Incidence of Cardiac Events in
      Patients with Small Cell Lung Cancer.
AB  - PURPOSE: Cardiac radiation dose was a predictor of inferior overall survival in
      the Radiation Therapy Oncology Group 0617 non-small cell lung cancer trial. We
      examined the association between radiation therapy (RT) and cardiac events (CE)
      for patients with small cell lung cancer (SCLC). METHODS AND MATERIALS: The US
      population-based Surveillance, Epidemiology, and End Results Program and Medicare
      claims databases were queried for rates of CE among patients with SCLC treated
      with chemotherapy (CTX) +/- RT. Propensity score matching (PSM) and multivariate
      analysis were conducted. Patients were matched for actual/theoretical RT start
      date (to prevent immortal time bias) and then full PSM balanced clinical
      characteristics. Cumulative incidence function curves were generated. RESULTS:
      From 2000 to 2011, 7060 patients were included: 2892 limited-stage SCLC (LS-SCLC)
      and 4168 extensive-stage SCLC. Grouping LS-SCLC and extensive-stage SCLC
      together, the incidence of CE for the CTX + RT and CTX-only groups was 44.1%
      versus 39% at 60 months (P = .008). After PSM (5286 patients), the incidence of
      CE for the CTX + RT and CTX-only groups was 43% versus 38.6% at 60 months (P =
      .033). Analysis of only LS-SCLC (2016 patients) demonstrated that the incidence
      of CE for CTX + RT versus CTX-only groups was 50.3% versus 42% at 60 months (P =
      .0231). Multivariate analysis again demonstrated an association between CE and RT
      (hazard ratio 1.20; 95% confidence interval 1.06-1.37; P = .005). After PSM (1614
      patients), the incidence of CE for CTX + RT versus CTX-only groups was 51.7%
      versus 41.6% at 60 months (P = .0042). CONCLUSIONS: Patients with SCLC are at
      significant risk of developing CE posttreatment; RT is associated with an
      absolute increase in the rate of CE at 5 years of approximately 5% for all
      patients with SCLC and up to 10% for patients with LS-SCLC. Cardiac risk
      management and cardiac-sparing RT techniques should be further evaluated for
      patients with SCLC.

PMID- 30191871
TI  - Localized Myxofibrosarcomas: Roles of Surgical Margins and Adjuvant Radiation
      Therapy.
AB  - PURPOSE: The objective of this study was to describe the outcome and prognostic
      factors for adults treated for localized myxofibrosarcoma. METHODS AND MATERIALS:
      We conducted a retrospective multicenter study of 425 nonmetastatic patients who
      underwent surgery between January 1996 and December 2015 in French National Group
      and were enrolled in the Conticabase. Pathologic diagnosis was systematically
      reviewed by expert pathologists. The endpoints were relapse-free and metastasis
      free survival. Log-rank tests and Cox models have been used to identified
      prognostic factors. RESULTS: Median age was 66 years; 53% were males; 85% of
      cases occurred in limbs or superficial trunk; median size was 60 mm; 47% and 39%
      were grades 2 and 3, respectively; 66% had R0 resection and 34% R1 resection.
      Adjuvant radiation therapy was given to 65% of patients, neoadjuvant radiation
      therapy to 3%, neoadjuvant chemotherapy to 7%, and adjuvant chemotherapy to 13%.
      The median follow-up was 51 months. The 5-year local relapse-free survival was
      67%; independent prognostic factors for local relapse were R1 resection (hazard
      ratio [HR] = 1.26; P = .001) and adjuvant radiation therapy (HR = 0.35; P =
      .0001) (ie, R1 resection and no adjuvant radiation therapy increase the hazard
      ratio). In stratified analysis, adjuvant radiation therapy was beneficial after
      R0 resection (P = .0020) and after R1 resection (P = .0001). The 5-year overall
      survival was 80%. The 5-year metastasis-free survival was 83%. Independent
      prognostic factors for metastatic relapse were grade 3 disease (HR = 1.975; P =
      .0001) and tumor size (HR = 1.006; P = .001). CONCLUSIONS: This large series of
      myxofibrosarcoma confirms the high rate of local relapse. Combination of R0
      resection and adjuvant radiation therapy provided the best local control. In
      parallel with an increasing rate of R0 resection and adjuvant radiation therapy,
      we observed a constant improvement in both metastatic and local relapse-free
      survival during the study.

PMID- 30191872
TI  - Therapeutic Effects of Human Umbilical Cord-Derived Mesenchymal Stem Cells on
      Canine Radiation-Induced Lung Injury.
AB  - PURPOSE: To investigate the effect of human umbilical cord-derived mesenchymal
      stem cell (MSC) transplantation on canine radiation-induced lung injury. METHODS
      AND MATERIALS: Beagle dogs received localized 15-Gy x-ray radiation to the right
      lower lung to establish the model of radiation-induced lung injury. After 180
      days, dogs were divided into 2 groups (4 per group). The MSC group received
      intratracheal MSC transplantation, and the saline group received the same volume
      of normal saline by lavage. The effect of MSC transplantation on lung injury was
      then evaluated 180 days after transplantation. RESULTS: At 180 days after 15-Gy
      radiation, canine arterial blood oxygen partial pressure was significantly
      decreased, and the levels of hydroxyproline and transforming growth factor (TGF)
      beta in peripheral blood were significantly increased, whereas that of TGF-alpha
      was significantly decreased. Computed tomography evaluation revealed visible
      honeycomb shadows in the right middle and lower pulmonary pleurae. Blood oxygen
      partial pressure of the MSC group gradually increased over time, whereas the
      levels of hydroxyproline and TGF-beta in the peripheral blood showed a decreasing
      trend; TGF-alpha levels gradually increased, which differed significantly from
      the results observed in the saline group. In addition, computed tomography and
      pathologic examination showed that the degree of lung injury in the MSC group was
      milder. The MSC group also showed significantly increased pulmonary superoxide
      dismutase levels and significantly decreased tumor necrosis factor-alpha,
      Interleukein-1, and hyaluronic acid levels. Further study confirmed that MSC
      transplantation inhibited the activation of TGF-beta-Smad2/3 in lung tissues, and
      in vitro experiments showed that medium conditioned with MSCs effectively
      inhibited the increase in Smad2 and 3 levels induced by TGF-beta1. CONCLUSION:
      Canine radiation-induced lung injury could be observed at 180 days after
      radiation at 15 Gy. MSC transplantation can reduce oxidative stress, inflammatory
      reactions, and TGF-beta-Smad2/3 pathway activation, thereby reducing lung injury.

PMID- 30191873
TI  - Severe PATCHED1 Deficiency in Cancer-Prone Gorlin Patient Cells Results in
      Intrinsic Radiosensitivity.
AB  - PURPOSE: Gorlin syndrome (or basal-cell nevus syndrome) is a cancer-prone genetic
      disease in which hypersusceptibility to secondary cancer and tissue reaction
      after radiation therapy is debated, as is increased radiosensitivity at cellular
      level. Gorlin syndrome results from heterozygous mutations in the PTCH1 gene for
      60% of patients, and we therefore aimed to highlight correlations between
      intrinsic radiosensitivity and PTCH1 gene expression in fibroblasts from adult
      patients with Gorlin syndrome. METHODS AND MATERIALS: The radiosensitivity of
      fibroblasts from 6 patients with Gorlin syndrome was determined by cell-survival
      assay after high (0.5-3.5 Gy) and low (50-250 mGy) gamma-ray doses. PTCH1 and DNA
      damage response gene expression was characterized by real-time polymerase chain
      reaction and Western blotting. DNA damage and repair were investigated by
      gammaH2AX and 53BP1 foci assay. PTCH1 knockdown was performed in cells from
      healthy donors by using stable RNA interference. Gorlin cells were genotyped by 2
      complementary sequencing methods. RESULTS: Only cells from patients with Gorlin
      syndrome who presented severe deficiency in PATCHED1 protein exhibited a
      significant increase in cellular radiosensitivity, affecting cell responses to
      both high and low radiation doses. For 2 of the radiosensitive cell strains,
      heterozygous mutations in the 5' end of PTCH1 gene explain PATCHED1 protein
      deficiency. In all sensitive cells, DNA damage response pathways (ATM, CHK2, and
      P53 levels and activation by phosphorylation) were deregulated after irradiation,
      whereas DSB repair recognition was unimpaired. Furthermore, normal cells with RNA
      interference-mediated PTCH1 deficiency showed reduced survival after irradiation,
      directly linking this gene to high- and low-dose radiosensitivity. CONCLUSIONS:
      In the present study, we show an inverse correlation between PTCH1 expression
      level and cellular radiosensitivity, suggesting an explanation for the
      conflicting results previously reported for Gorlin syndrome and possibly
      providing a basis for prognostic screens for radiosensitive patients with Gorlin
      syndrome and PTCH1 mutations.

PMID- 30191874
TI  - Automated Instead of Manual Treatment Planning? A Plan Comparison Based on Dose
      Volume Statistics and Clinical Preference.
AB  - PURPOSE: Automated planning aims to speed up treatment planning and improve plan
      quality. We compared manual planning with automated planning for lung
      stereotactic body radiation therapy based on dose-volume histogram statistics and
      clinical preference. METHODS AND MATERIALS: Manual and automated intensity
      modulated radiation therapy plans were generated for 56 patients by use of
      software developed in-house and Pinnacle 9.10 Auto-Planning, respectively.
      Optimization times were measured in 10 patients, and the impact of the automated
      plan (AP) on the total treatment cost was estimated. For the remaining 46
      patients, each plan was checked against our clinical objectives, and a pair-wise
      dose-volume histogram comparison was performed. Three experienced radiation
      oncologists evaluated each plan and indicated their preference. RESULTS: APs
      reduced the average optimization time by 77.3% but only affected the total
      treatment cost by 3.6%. Three APs and 0 manual plans failed our clinical
      objectives, and 13 APs and 9 manual plans showed a minor deviation. APs
      significantly reduced D2% (2% of the volume receives a dose of at least D2%) for
      the spinal cord, esophagus, heart, aorta, and main stem bronchus (P < .05) while
      preserving target coverage. The radiation oncologists found >75% of the APs
      clinically acceptable without any further fine-tuning. CONCLUSIONS: APs may help
      to create satisfactory treatment plans quickly and effectively. Because critical
      appraisal by qualified professionals remains necessary, there is no such thing as
      "fully automated" planning yet.

PMID- 30191875
TI  - Hepatocellular Carcinoma Tumor Dose Response After 90Y-radioembolization With
      Glass Microspheres Using 90Y-SPECT/CT-Based Voxel Dosimetry.
AB  - PURPOSE: To investigate hepatocellular carcinoma tumor dose-response
      characteristics based on voxel-level absorbed doses (D) and biological effective
      doses (BED) using quantitative 90Y-single-photon emission computed tomography
      (SPECT)/computed tomography (CT) after 90Y-radioembilization with glass
      microspheres. We also investigated the relationship between normal liver D and
      toxicities. METHODS AND MATERIALS: 90Y-radioembolization activity distributions
      for 34 patients were based on quantitative 90Y-bremsstrahlung SPECT/CT. D maps
      were generated using a local-deposition algorithm. Contrast-enhanced CT or
      magnetic resonance imaging scans of the liver were registered to 90Y-SPECT/CT,
      and all tumors larger than 2.5 cm diameter (53 tumors) were segmented. Tumor mean
      D and BED (Dmean and BEDmean) and dose volume coverage from 0% to 100% in 10%
      steps (D0-D100 and BED0-BED100) were extracted. Tumor response was evaluated on
      follow-up using World Health Organization (WHO), Response Evaluation Criteria in
      Solid Tumors (RECIST), and modified RECIST (mRECIST) criteria. Differences in
      dose metrics for responders and nonresponders were assessed using the Mann
      Whitney U test. A univariate logistic regression model was used to determine
      tumor dose metrics that correlated with tumor response. Correlations among tumor
      size, tumor Dmean, and tumor dose heterogeneity (defined as the coefficient of
      variation) were assessed. RESULTS: The objective response rates were 14 of 53, 15
      of 53, and 30 of 53 for WHO, RECIST, and mRECIST criteria, respectively. WHO and
      RECIST response statuses did not correlate with D or BED. For mRECIST responders
      and nonresponders, D and BED were significantly different for Dmean, D20 to D80,
      BEDmean, and BED0 to BED80. Threshold doses (and the 95% confidence interval) for
      50% probability of mRECIST response (D50%) were 160 Gy (123-196 Gy) for Dmean and
      214 Gy (146-280 Gy) for BEDmean. Tumor dose heterogeneity significantly
      correlated with tumor volume. No statistically significant association between
      Dmean to normal liver and complications related to bilirubin, albumin, or ascites
      was observed. CONCLUSIONS: Hepatocellular carcinoma tumor dose-response curves
      after 90Y-radioembolization with glass microspheres showed Dmean of 160 Gy and
      BEDmean of 214 Gy for D50% with a positive predictive value of ~70% and a
      negative predictive value of ~62%. No complications were observed in our patient
      cohort for normal liver Dmean less than 44 Gy.

PMID- 30191876
TI  - In Regard to United Nations.

PMID- 30191878
TI  - In Regard to You et al and Teixido et al.

PMID- 30191877
TI  - Expanding Access to Radiation Therapy: An Update on Brazil's Current Challenges
      and Opportunities.

PMID- 30191879
TI  - In Regard to Zeidan et al.

PMID- 30191880
TI  - In Reply to Belkacemi and Tsoutsou.

PMID- 30191881
TI  - In Regard to Sura et al.

PMID- 30191882
TI  - In Reply to McClelland and Jaboin.

PMID- 30191883
TI  - Erratum to: Comparison of Adjuvant Versus Salvage Radiotherapy Policies for
      Postprostatectomy Radiotherapy. Int J Radiat Oncol Biol Phys 2004;59:329-340.

PMID- 30191884
TI  - Study of direct bandgap type-I GeSn/GeSn double quantum well with improved
      carrier confinement.
AB  - The GeSn-based quantum wells (QWs) have been investigated recently for the
      development of efficient GeSn emitters. Although our previous study indicated
      that the direct bandgap well with type-I band alignment was achieved, the
      demonstrated QW still has insufficient carrier confinement. In this work, we
      report the systematic study of light emission from the
      Ge0.91Sn0.09/Ge0.85Sn0.15/Ge0.91Sn0.09 double QW structure. Two double QW
      samples, with the thicknesses of Ge0.85Sn0.15 well of 6 and 19 nm, were
      investigated. Band structure calculations revealed that both samples feature type
      I band alignment. Compared with our previous study, by increasing the Sn
      composition in GeSn barrier and well, the QW layer featured increased energy
      separation between the indirect and direct bandgaps towards a better direct gap
      semiconductor. Moreover, the thicker well sample exhibited improved carrier
      confinement compared to the thinner well sample due to lowered first quantized
      energy level in the Gamma valley. To identify the optical transition
      characteristics, photoluminescence (PL) study using three pump lasers with
      different penetration depths and photon energies was performed. The PL spectra
      confirmed the direct bandgap well feature and the improved carrier confinement,
      as significantly enhanced QW emission from the thicker well sample was observed.

PMID- 30191885
TI  - The Kondo resonance line shape in scanning tunnelling spectroscopy: instrumental
      aspects.
AB  - In the scanning tunnelling microscope, the many-body Kondo effect leads to a zero
      bias feature of the differential conductance spectra of magnetic adsorbates on
      surfaces. The intrinsic line shape of this Kondo resonance and its temperature
      dependence in principle contain valuable information. We use measurements on a
      molecular Kondo system, all- trans retinoic acid on Au(1 1 1), and model
      calculations to discuss the role of instrumental broadening. The modulation
      voltage used for the lock-in detection, noise on the sample voltage, and the
      temperature of the microscope tip are considered. These sources of broadening
      affect the apparent line shapes and render difficult a determination of the
      intrinsic line width, in particular when variable temperatures are involved.

PMID- 30191886
TI  - Manipulation of random telegraph signals in a silicon nanowire transistor with a
      triple gate.
AB  - Manipulation of carrier densities at the single electron level is inevitable in
      modern silicon based transistors to ensure reliable circuit operation with
      sufficiently low threshold-voltage variations. However, previous methods required
      statistical analysis to identify devices which exhibit random telegraph signals
      (RTSs), caused by trapping and de-trapping of a single electron. Here, we show
      that we can deliberately introduce an RTS in a silicon nanowire transistor, with
      its probability distribution perfectly controlled by a triple gate. A quantum dot
      (QD) was electrically defined in a silicon nanowire transistor with a triple
      gate, and an RTS was observed when two barrier gates were negatively biased to
      form potential barriers, while the entire nanowire channel was weakly inverted by
      the top gate. We could successfully derive the energy levels in the QD from the
      quantum mechanical probability distributions and the average lifetimes of RTSs.
      This study reveals that we can manipulate individual electrons electrically, even
      at room temperature, and paves the way to use a charged state for quantum
      technologies in the future.

PMID- 30191887
TI  - Nanofibrous yarn reinforced HA-gelatin composite scaffolds promote bone formation
      in critical sized alveolar defects in rabbit model.
AB  - Alveolar ridge resorption and crestal bone loss necessitate the use of bone graft
      substitutes for dental rehabilitation. The aim of this study was to compare the
      bone regenerative property of nanofibre incorporated two composite matrices
      (nanofibrous sheet layered matrix (CS-S) and nanofibrous yarn reinforced matrix
      (CS-Y)) in critical sized mandibular defect in a rabbit model (under load bearing
      scenario). Histological evaluation revealed continuous bone formation in the
      defect implanted with fibre reinforced scaffolds than those without fibres as
      well as commercial nanoHA-collagen graft. Interestingly, the mineralisation and
      the mineral density were significantly higher with nanoyarn reinforced scaffolds.
      Moreover, the compressive strength of new bone formed from CS-Y scaffolds was
      almost similar to that of native rabbit mandible. It can be concluded that the
      mechanical strength provided by three-dimensionally reinforced nanoyarns in the
      matrix could promote bone formation in load bearing mandibular region, and these
      can be proposed as a scaffold of choice for alveolar bone augmentation and dental
      rehabilitation.

PMID- 30191889
TI  - Synthesis of biologically-active reduced graphene oxide by using fucoidan as a
      multifunctional agent for combination cancer therapy.
AB  - A therapeutic reduced graphene oxide (RGO) is synthesized by using fucoidan (Fu)
      as the reducing and surface functionalizing agent. The synthesized Fu-RGO
      exhibits promising characteristics for therapeutic applications such as high
      dispersity in aqueous media, biocompatibility, selective cytotoxicity to cancer
      cells, high loading capacity of the anticancer drug, and photothermal conversion
      effect. Therefore, Fu-GO is successfully harnessed as a combinatorial cancer
      treatment platform through bio-functional (Fu), chemo (doxorubicin (Dox)) and
      photothermal (RGO with near-infrared irradiation) modalities.

PMID- 30191888
TI  - Comparative cytocompatibility of multiple candidate cell types to
      photoencapsulation in PEGNB/PEGDA macroscale or microscale hydrogels.
AB  - The encapsulation of live cells into photopolymerized hydrogel scaffolds has the
      potential to augment or repair tissue defects, establish versatile regenerative
      medicine strategies, and be developed as well-defined, yet tunable
      microenvironments to study fundamental cellular behavior. However, hydrogel
      fabrication limitations constrain most studies to macroscale hydrogel scaffolds
      encapsulating millions of cells. These macroscale materials possess regions of
      heterogeneous photopolymerization conditions and are therefore poor platforms to
      identify the response of individual cells to encapsulation. Recently,
      microfluidic droplet-based hydrogel miniaturization and cell encapsulation offers
      high-throughput, reproducible, and continuous fabrication. Reports of post
      encapsulation cell viability, however, vary widely among specific techniques.
      Furthermore, different cell types often exhibit different level of tolerance to
      photoencapsulation-induced toxicity. Accordingly, we evaluate the cellular
      tolerance of various encapsulation techniques and photopolymerization parameters
      for four mammalian cell types, with potential applications in tissue
      regeneration, using polyethylene glycol diacrylate or polyethylene glycol
      norbornene (PEGNB) hydrogels on micro- and macro-length scales. We found PEGNB
      provides excellent cellular tolerance and supports long-term cell survival by
      mitigating the deleterious effects of acrylate photopolymerization, which are
      exacerbated at diminishing volumes. PEGNB, therefore, is an excellent candidate
      for hydrogel miniaturization. PEGNB hydrogel properties, however, were found to
      have variable effects on encapsulating different cell candidates. This study
      could provide guidance for cell encapsulation practices in tissue engineering and
      regenerative medicine research.

PMID- 30191890
TI  - Tb3Pd2, Er3Pd2 and Er6Co5-x: structural variations and bonding in rare-earth
      richer binary intermetallics.
AB  - The three binary Tb/Er-rich transition metal compounds Tb3Pd2 (triterbium
      dipalladium), Er3Pd2 (trierbium dipalladium) and Er6Co5-x (hexaerbium
      pentacobalt) crystallize in the space groups Pbam (Pearson symbol oP20), P4/mbm
      (tP10) and P63/m (hP22), respectively. Single crystals of Tb3Pd2 and Er6Co5-x
      suitable for X-ray structure analysis were obtained using rare-earth halides as a
      flux. Tb3Pd2 adopts its own structure type, which can be described as a
      superstructural derivative of the U3Si2 type, which is the type adopted by
      Er3Pd2. Compound Er6Co5-x belongs to the Ce6Co2-xSi3 family. All three compounds
      feature fused tricapped {TR6} (R = rare-earth metal and T = transition metal)
      trigonal prismatic heterometallic clusters. R3Pd2 is reported to crystallize in
      the U3Si2 type; however, our more detailed structure analysis reveals that
      deviations occur with heavier R elements. Similarly, Er6Co5-x was assumed to be
      stoichiometric Er4Co3 = Er6Co4.5. Our studies reveal that it has a single
      defective transition-metal site leading to the composition Er6Co4.72(2). LMTO
      (linear muffin-tin orbital)-based electronic structure calculations suggest the
      strong domination of heteroatomic bonding in all three structures.

PMID- 30191891
TI  - Supramolecular structures of rhenium(I) complexes mediated by ligand planarity
      via the interplay of substituents.
AB  - The crystal and molecular structures of two ReI tricarbonyl complexes, namely fac
      tricarbonylchlorido[1-(4-fluorocinnamoyl)-3-(pyridin-2-yl-kappaN)pyrazole
      kappaN2]rhenium(I), [ReCl(C17H12FN3O)(CO)3], (I), and fac-tricarbonylchlorido[1
      (4-nitrocinnamoyl)-3-(pyridin-2-yl-kappaN)pyrazole-kappaN2]rhenium(I) acetone
      monosolvate, [ReCl(C17H12ClN4O3)(CO)3].C3H6O, (II), are reported. The complexes
      form centrosymmetric dimers that are linked into one-dimensional columns by C
      H...Cl and N-O...H interactions in (I) and (II), respectively. C-H...Cl
      interactions in (II) generate two R21(7) loops that merge into a single R21(10)
      loop. These interactions involve the alkene, pyrazole and benzene rings, hence
      restricting the ligand rotation and giving rise to a planar conformation. Unlike
      (II), complex (I) exhibits a twisted conformation of the ligand and a pair of
      molecules forms a centrosymmetric dimer with an R22(10) loop via C-H...O
      interactions. The unique supramolecular structures of (I) and (II) are determined
      by their planarity and weak interactions. The planar conformation of (II)
      provides a base for appreciable pi-pi stacking interactions compared to (I). In
      addition, an N-O...pi interaction stabilizes the supramolecular structure of
      (II). We report herein the first n->pi* interactions of ReI tricarbonyl
      complexes, which account for 0.33 kJ mol-1. Intermolecular C-H...Cl and C-H...O
      interactions are present in both complexes, with (II) showing a greater
      preference for these interactions compared to (I), with cumulative contributions
      of 48.7 and 41.5%, respectively. The influence of inductive (fluoro) and/or
      resonance (nitro) effects on the pi-stacking ability was further supported by
      LOLIPOP (localized orbital locator-integrated pi over plane) analysis. The
      benzene ring of (II) demonstrated a higher pi-stacking ability compared to that
      of (I), which is supported by the intrinsic planar geometry. The HOMA (harmonic
      oscillator model of aromaticity) index of (I) revealed more aromaticity with
      respect to (II), suggesting that NO2 greatly perturbed the aromaticity. The
      Hirshfeld fingerprint (FP) plots revealed the preference of (II) over (I) for pi
      pi contacts, with contributions of 6.8 and 4.4%, respectively.

PMID- 30191892
TI  - Design of two series of 1:1 cocrystals involving 4-amino-5-chloro-2,6
      dimethylpyrimidine and carboxylic acids.
AB  - Two series of a total of ten cocrystals involving 4-amino-5-chloro-2,6
      dimethylpyrimidine with various carboxylic acids have been prepared and
      characterized by single-crystal X-ray diffraction. The pyrimidine unit used for
      the cocrystals offers two ring N atoms (positions N1 and N3) as proton-accepting
      sites. Depending upon the site of protonation, two types of cations are possible
      [Rajam et al. (2017). Acta Cryst. C73, 862-868]. In a parallel arrangement, two
      series of cocrystals are possible depending upon the hydrogen bonding of the
      carboxyl group with position N1 or N3. In one series of cocrystals, i.e. 4-amino
      5-chloro-2,6-dimethylpyrimidine-3-bromothiophene-2-carboxylic acid (1/1), 1, 4
      amino-5-chloro-2,6-dimethylpyrimidine-5-chlorothiophene-2-carboxylic acid (1/1),
      2, 4-amino-5-chloro-2,6-dimethylpyrimidine-2,4-dichlorobenzoic acid (1/1), 3, and
      4-amino-5-chloro-2,6-dimethylpyrimidine-2-aminobenzoic acid (1/1), 4, the
      carboxyl hydroxy group (-OH) is hydrogen bonded to position N1 (O-H...N1) of the
      corresponding pyrimidine unit (single point supramolecular synthon). The
      inversion-related stacked pyrimidines are doubly bridged by the carboxyl groups
      via N-H...O and O-H...N hydrogen bonds to form a large cage-like tetrameric unit
      with an R42(20) graph-set ring motif. These tetrameric units are further
      connected via base pairing through a pair of N-H...N hydrogen bonds, generating
      R22(8) motifs (supramolecular homosynthon). In the other series of cocrystals,
      i.e. 4-amino-5-chloro-2,6-dimethylpyrimidine-5-methylthiophene-2-carboxylic acid
      (1/1), 5, 4-amino-5-chloro-2,6-dimethylpyrimidine-benzoic acid (1/1), 6, 4-amino
      5-chloro-2,6-dimethylpyrimidine-2-methylbenzoic acid (1/1), 7, 4-amino-5-chloro
      2,6-dimethylpyrimidine-3-methylbenzoic acid (1/1), 8, 4-amino-5-chloro-2,6
      dimethylpyrimidine-4-methylbenzoic acid (1/1), 9, and 4-amino-5-chloro-2,6
      dimethylpyrimidine-4-aminobenzoic acid (1/1), 10, the carboxyl group interacts
      with position N3 and the adjacent 4-amino group of the corresponding pyrimidine
      ring via O-H...N and N-H...O hydrogen bonds to generate the robust R22(8)
      supramolecular heterosynthon. These heterosynthons are further connected by N
      H...N hydrogen-bond interactions in a linear fashion to form a chain-like
      arrangement. In cocrystal 1, a Br...Br halogen bond is present, in cocrystals 2
      and 3, Cl...Cl halogen bonds are present, and in cocrystals 5, 6 and 7, Cl...O
      halogen bonds are present. In all of the ten cocrystals, pi-pi stacking
      interactions are observed.

PMID- 30191893
TI  - Thermal stability of the layered modification of Cu0.5ZrTe2 in the temperature
      range 25-900  degrees C.
AB  - The thermal stability of the layered modification of the Cu0.5ZrTe2
      polycrystalline intercalation compound, synthesized at room temperature, has been
      studied in the temperature range 25-900  degrees C. A change in the occupation of
      the octahedral and tetrahedral coordinated sites in the interlayer space of the
      zirconium ditelluride was observed using in-situ time-resolved synchrotron X-ray
      powder diffraction experiments. The formation of the rhombohedral CuZr2Te4 phase,
      which is stable in the temperature range 300-700  degrees C, has been observed.
      The copper intercalation at room temperature leads to the formation of a phase in
      which the Cu atoms occupy only octahedral sites in the interlayer space. At
      temperatures above the decay temperature of the rhombohedral CuZr2Te4, a layered
      phase with Cu atoms uniformly distributed between octahedral and tetrahedral
      sites in the interlayer space is stable. The changes in the crystal structure
      independent of temperature are in agreement with the previously proposed model,
      according to which the stability of the layered or the rhombohedral phase is
      determined by the entropy factor associated with the distribution of the
      intercalated atoms between the octahedral and tetrahedral sites in the interlayer
      space.

PMID- 30191894
TI  - Composite host lattices of 4,4'-sulfonyldibenzoate water/boric acid in two
      tetrapropylammonium inclusion compounds.
AB  - Two novel inclusion compounds of 4,4'-sulfonyldibenzoate anions and
      tetrapropylammonium cations with different ancillary molecules of water and boric
      acid, namely bis(tetrapropylammonium) 4,4'-sulfonyldibenzoate dihydrate,
      2C12H28N+.C14H8O6S2-.H2O (1), and bis(tetrapropylammonium) 4,4'
      sulfonyldibenzoate bis(boric acid), 2C12H28N+.C14H8O6S2-.2H3BO3 (2), were
      prepared and characterized using single-crystal X-ray diffraction. In the two
      salts, the host 4,4'-sulfonyldibenzoic acid molecules, which are converted to the
      corresponding anions under basic conditions, can be regarded as proton acceptors
      which link different proton donors of the ancillary molecules of water or boric
      acid. In this way, an isolated hydrogen-bonded tetramer is constructed in salt 1
      and a ribbon is constructed in salt 2. The tetramers and ribbons are then packed
      in a repeating manner to generate various host frameworks, and the
      tetrapropylammonium guest counter-ions are contained in the cavities of the host
      lattices to give the final stable crystal structures. In these two salts,
      although the host anion and guest cation are the same, the difference in the
      ancillary small molecules results in different structures, indicating the
      significance of ancillary molecules in the formation of crystal structures.

PMID- 30191895
TI  - A thermally stable three-dimensional cobalt(II) coordination polymer based on the
      V-shaped ligand 4-(4-carboxyphenoxy)isophthalate.
AB  - A new cobalt(II) coordination polymer (CP), poly[[bis[MU6-4-(4
      carboxylatophenoxy)benzene-1,3-dicarboxylato-kappa6O1:O1:O3:O3':O4:O4']bis(1,10
      phenanthroline-kappa2N,N')tricobalt(II)] 0.72-hydrate],
      {[Co3(C15H7O7)2(C12H8N2)2].0.72H2O}n, (I), is constructed from CoII ions and 4-(4
      carboxyphenoxy)isophthalate (cpoia3-) and 1,10-phenanthroline (phen) ligands.
      Based on centrosymmetric trinuclear [Co3(phen)2(COO)6] secondary building units
      (SBUs), the structure of (I) is a three-dimensional CP with a (3,6)-connected net
      and point symbol (42.6)2(44.62.87.102). The positions of four [Co3(phen)2(COO)6]
      SBUs and four cpoia3- ligands reproduce a Chinese-knot-shaped arrangement along
      the ab plane. (I) has been characterized by single-crystal X-ray diffraction, IR
      spectroscopy, powder X-ray diffraction (PXRD) and thermostability analysis. It
      shows a good thermal stability from room temperature to 673 K. In addition, the
      temperature dependence of the magnetic properties was measured.

PMID- 30191896
TI  - Models for potential dendritic nitric oxide donors: crystal structures of two 2
      nitroanilino precursors and nitric oxide-release behavior of the nitrosated
      derivatives.
AB  - Two molecular precursors to dendrimeric materials that could serve as slow and
      sustained NO-releasing therapeutic agents have been synthesized and
      characterized. N1,N4-Bis(2-nitrophenyl)butane-1,4-diamine, C16H18N4O4, (I),
      crystallizes in a lattice with equal populations of two molecules of different
      conformations, both of which possess inversion symmetry through the central C-C
      bond. One molecule has exclusively anti conformations along the butyl chain,
      while the other has a gauche conformation of the substituents on the first C-C
      bond. N2,N2-Bis[2-(2-nitroanilino)ethyl]-N1-(2-nitrophenyl)ethane-1,2-diamine,
      C24H27N7O6, (II), crystallizes with one unique molecule in the asymmetric unit.
      Neighboring pairs of molecules are linked into dimers via N-H...O amine-nitro
      hydrogen bonds. The dimers are assembled into layers that stack in an A-B-A-B
      sequence such that the repeat distance in the stacking direction is over 46 A.
      Molecular NO-release agents N1,N4-bis(2-nitrophenyl)-N1,N4-dinitrosobutane-1,4
      diamine, C16H16N6O6, (III), and N1-(2-nitrophenyl)-N2,N2-bis{2-[(2
      nitrophenyl)(nitroso)amino]ethyl}-N1-nitrosoethane-1,2-diamine, C24H24N10O9,
      (IV), were prepared via treatment of (I) and (II), respectively, with NaNO2 and
      acetic acid. The release of NO from solid-phase samples of (III) and (IV)
      suspended in phosphate buffer was monitored spectroscopically over a period of 21
      days. Although (IV) released a greater amount of NO, as expected due to it having
      three NO moieties for every two in (III), the (IV):(III) ratio of the rate and
      extent of NO release was significantly less than 1.5:1, suggesting that some
      combination of electronic, chemical, and/or steric factors may be affecting the
      release process.

PMID- 30191898
TI  - Construction and photoluminescence properties of a three-dimensional ZnII
      coordination network based on naphthalene-1,4-dicarboxylic acid and 1,6
      bis(pyridin-3-yl)-1,3,5-hexatriene.
AB  - In recent years, coordination polymers constructed from multidentate carboxylate
      and pyridyl ligands have attracted much attention because these ligands can adopt
      a rich variety of coordination modes and thus lead to the formation of
      crystalline products with intriguing structures and interesting properties. A new
      coordination polymer, namely poly[[MU2-1,6-bis(pyridin-3-yl)-1,3,5-hexatriene
      kappa2N:N'](MU3-naphthalene-1,4-dicarboxylato-kappa4O1,O1':O4:O4')zinc(II)],
      [Zn(C12H6O4)(C16H14N2)]n, has been prepared by the self-assembly of
      Zn(NO3)2.6H2O, naphthalene-1,4-dicarboxylic acid (1,4-H2ndc) and 1,6-bis(pyridin
      3-yl)-1,3,5-hexatriene (3,3'-bphte) under hydrothermal conditions. The title
      compound has been structurally characterized by IR spectroscopy, elemental
      analysis, powder X-ray diffraction and single-crystal X-ray diffraction analysis.
      Each ZnII ion is six-coordinated by four O atoms from three 1,4-ndc2- ligands and
      by two N atoms from two 3,3'-bphte ligands, forming a distorted octahedral ZnO4N2
      coordination geometry. Pairs of ZnII ions are linked by 1,4-ndc2- ligands,
      leading to the formation of a two-dimensional square lattice (sql) layer
      extending in the ab plane. In the crystal, adjacent layers are further connected
      by 3,3'-bphte bridges, generating a three-dimensional architecture. From a
      topological viewpoint, if each dinuclear zinc unit is considered as a 6-connected
      node and the 1,4-ndc2- and 3,3'-bphte ligands are regarded as linkers, the
      structure can be simplified as a unique three-dimensional 6-connected framework
      with the point symbol 446108. The thermal stability and solid-state
      photoluminescence properties have also been investigated.

PMID- 30191897
TI  - Novel tantalum phosphate Na13Sr2Ta2(PO4)9: synthesis, crystal structure, DFT
      calculations and Dy3+-activated fluorescence performance.
AB  - A new tantalum phosphate, tridecasodium distrontium ditantalum nonaphosphate,
      Na13Sr2Ta2(PO4)9, was prepared using the high-temperature flux method. The
      structure can be described as a three-dimensional open framework containing
      isolated [TaV2(PO4)9]17- units that are interlocked by Na and Sr ions. Band
      structure studies by the first-principles method revealed that Na13Sr2Ta2(PO4)9
      is an insulator with an indirect band gap of 4.78 eV, which makes it suitable as
      a luminescent host matrix. A series of solid solutions, i.e. Na13Sr2
      xTa2(PO4)9:xDy3+ (x = 0.01, 0.02, 0.04, 0.06, 0.08, 0.1, 0.12 and 0.14), were
      prepared and their photoluminescence properties studied. Under 350 nm light
      excitation, these emit two typical emissions of the Dy3+ ion, i.e. the 4F9/2
      >6H15/2 transition centred at 476 nm and the 4F9/2->6H13/2 transition centred at
      570 nm.

PMID- 30191899
TI  - Theoretical insight into the disordered structure of (Z)-2-[(E)-(4
      methoxybenzylidene)hydrazinylidene]-1,2-diphenylethanone: the role of noncovalent
      interactions.
AB  - A global glide disorder has been discovered during an X-ray investigation of the
      crystal structure of (Z)-2-[(E)-(4-methoxybenzylidene)hydrazinylidene]-1,2
      diphenylethanone (MHDE, C22H18N2O2) at room temperature. In another crystal,
      however, such disorder disappears (still at room temperature). Even though the
      disorder may be partly due to the poor quality of the harvested crystal, the
      structure can shed light on the nature of disorder. With the help of quantum
      chemical calculations, it is found that the global disorder seems to be connected
      with the need for stabilization of the somewhat rigid but mobile and unstable
      molecular structure. The most relevant feature driving the packing of the
      disordered structure concerns the slight perturbations (such as glide) of two or
      more disorder components (fractional occupancies) distributed throughout the
      crystal.

PMID- 30191901
TI  - Blended learning and an exploration of student expectations on a Master's
      prosthodontics programme with reassessment at five years.

PMID- 30191900
TI  - Hyperglycemia Predicts Blend Sign in Patients with Intracerebral Hemorrhage.
AB  - BACKGROUND Predictive values of admission blood glucose for early hematoma
      expansion in patients with intracranial hemorrhage (ICH) remain controversial.
      Blend sign is a novel image predictor for early hematoma growth that suggests
      presence of active bleeding. We investigated the association between
      hyperglycemia and blend sign in predicting early hematoma growth in ICH patients.
      MATERIAL AND METHODS All patients with intracranial hemorrhage were
      retrospectively reviewed. Clinical characteristics and radiological parameters
      were collected. Blood glucose was measured within 24 h after onset. CT scan
      results for hematoma expansion and blend sign were evaluated by 2 readers.
      Multivariate logistic regression analyses were applied to reveal the associations
      between hematoma growth and blend sign, as well as other variables. RESULTS Out
      of 164 patients with ICH, 52 exhibited early hematoma growth and 18 of these were
      diagnosed with blend sign. Average blood glucose was 7.53 mmol/L among all
      patients. By using multivariate analyses, the time of CT scan baseline, GCS
      score, hematoma size, blend sign, and blood glucose were associated with hematoma
      expansion, whereas only hyperglycemia was associated with blend sign. CONCLUSIONS
      Admission hyperglycemia is associated with hematoma expansion in the presence of
      blend sign. These findings suggest that elevated blood glucose is a possible
      factor predicting continuous bleeding. Strategies to control blood glucose and
      ameliorate hematoma growth are urgently needed and will be investigated in our
      future studies.

PMID- 30191902
TI  - Prepared for practice and equipped for employment: what do dental foundation
      trainers think of their trainees?

PMID- 30191904
TI  - Corrigendum.
AB  - [This corrects the article DOI: 10.2217/hep.14.7.].

PMID- 30191903
TI  - Professionalism by proxy: a case for the formal regulation of dental assistants
      in Australia.
AB  - Dental assistants are the most numerous member of the dental team in Australia,
      responsible for many clinical and non-clinical duties. Despite this, dental
      assistants are not registered and regulated in the same manner as their clinical
      colleagues within the dental profession. In this article, the authors argue that
      this is an unacceptable situation within the Australian dental context. In the
      examination of events within the profession both within Australia and overseas,
      it becomes apparent that this is an untenable position with regards to promoting
      the safety of the public. The current stance towards dental assistants is often
      perpetuated by a dental profession whose motives would not seem to be free from
      issues of professional dominance. Dental assistants may also be an essential
      division of the dental profession in providing culturally competent, economically
      viable and sustainable oral healthcare to those communities that are
      traditionally difficult to access.

PMID- 30191905
TI  - Quality governance - a call to arms.

PMID- 30191907
TI  - Care home residents admitted to hospital through the emergency pathway:
      characteristics and associations with inpatient mortality.
AB  - BACKGROUND: Routinely collected hospital information could help to understand the
      characteristics and outcomes of care home residents admitted to hospital as an
      emergency. METHODS: This retrospective 2-year service evaluation included first
      emergency admissions of any older adult (>=75 years) presenting to Cambridge
      University Hospital. Routinely collected patient variables were captured by an
      electronic patient record system. Care home status was established using an
      official register of care homes. RESULTS: 7.7% of 14,777 admissions were care
      home residents. They were older, frailer, more likely to be women and have
      cognitive impairment than those admitted from their own homes. Additionally, 42%
      presented with an Emergency Department Modified Early Warning Score above the
      threshold triggering urgent review, compared to 26% of older adults from their
      own homes. Admission from a care home was associated with higher 30-day inpatient
      mortality (11.1 vs 5.7%), which persisted after multivariable adjustment (hazard
      ratio: 1.42; 95% confidence interval: 1.09-1.83; p = 0.008). CONCLUSION: Care
      home residents admitted to hospital as an emergency have high illness acuity and
      inpatient mortality.

PMID- 30191906
TI  - Neurological complications in patients with Plasmodium vivax malaria from
      Karachi, Pakistan.
AB  - BACKGROUND: Malaria remains an endemic disease in Pakistan with an estimated
      healthcare burden of 1.6 million cases annually, with Plasmodium vivax accounting
      for 67% of reported cases. P. vivax is the most common species causing malaria
      outside of Africa, with approximately 13.8 million reported cases worldwide.
      METHOD: We report a series of P. vivax cases with cerebral involvement that
      presented at Aga Khan University Hospital, Karachi, Pakistan. RESULTS: The
      majority of the patients presented with high-grade fever accompanied by
      projectile vomiting and abnormal behaviour, seizures, shock and unconsciousness.
      Seven of 801 patients with P. vivax monoinfection presented or developed cerebral
      complications. P. vivax infections were diagnosed based on peripheral smears and
      rapid diagnostic testing. CONCLUSION: P. vivax infection can lead to severe
      complications, although not with the frequency of Plasmodium falciparum
      infection. Current cases highlight an increasing trend of cerebral complications
      caused by P. vivax.

PMID- 30191908
TI  - Does dermatoscopy facilitate the detection and diagnosis of vascular skin
      lesions? A case-control study.
AB  - BACKGROUND: During dermatoscope-guided surgical procedures, we noticed that
      vasculature was easily identified. This study investigated the use of
      dermatoscopy in detecting and diagnosing vascular skin lesions. METHODS: We
      retrieved records of patients with vascular skin lesions who underwent
      dermatoscopy over a 3 month period, in two outpatient clinics affiliated with a
      university teaching hospital. Our controls were similar patients where
      dermatoscopy was not performed. RESULTS: Our new findings are: 1, clinical and
      dermatoscopic examinations diagnosed significantly more patients with vascular
      skin lesions than clinical examinations alone (risk ratio: 1.36; 95% confidence
      interval: 1.10-1.67); 2, the detection rate increase was significant for cherry
      angiomas (p < 0.001), telangiectasias (p < 0.01) and spider angiomas (p < 0.01);
      3, qualitatively, dermatoscopy revealed characteristic configurations, hues and
      colour saturations of the vascular skin lesions; and 4, the first reported
      dermatoscopic images of focal essential telangiectasia and petechial angioma.
      CONCLUSION: In our setting, clinical and dermatoscopic examinations significantly
      facilitated detecting and diagnosing vascular skin lesions, compared to clinical
      examination alone.

PMID- 30191909
TI  - The key challenges of discussing end-of-life stroke care with patients and
      families: a mixed-methods electronic survey of hospital and community healthcare
      professionals.
AB  - BACKGROUND: Communication between professionals, patients and families about
      palliative and end-of-life care after stroke is complex and there is a need for
      educational resources in this area. METHODS: To explore the key learning needs of
      healthcare professionals, a multidisciplinary, expert group developed a short
      electronic survey with open and closed questions, and then distributed it to six
      UK multiprofessional networks and two groups of local clinicians. RESULTS: A
      total of 599 healthcare professionals responded. Educational topics that were
      either definitely or probably needed were: ensuring consistent messages to
      families and patients (88%); resolving conflicts among family members (83%);
      handling unrealistic expectations (88%); involving families in discussions
      without them feeling responsible for decisions (82%); discussion of prognostic
      uncertainties (79%); likely mode of death (72%); and oral feeding for 'comfort'
      in patients at risk of aspiration (71%). The free-text responses (n = 489) and 82
      'memorable' cases identified similar themes. CONCLUSION: Key topics of unmet need
      for education in end-of-life care in stroke have been identified and these have
      influenced the content of an open access, web-based educational resource.

PMID- 30191910
TI  - Cognitive bias in clinical medicine.
AB  - Cognitive bias is increasingly recognised as an important source of medical
      error, and is both ubiquitous across clinical practice yet incompletely
      understood. This increasing awareness of bias has resulted in a surge in clinical
      and psychological research in the area and development of various 'debiasing
      strategies'. This paper describes the potential origins of bias based on 'dual
      process thinking', discusses and illustrates a number of the important biases
      that occur in clinical practice, and considers potential strategies that might be
      used to mitigate their effect.

PMID- 30191911
TI  - Haemochromatosis arthropathy - a conundrum of the Celtic curse.
AB  - Genetic haemochromatosis is an autosomal recessive disorder, mostly due to HFE
      gene mutation, leading to loss of hepcidin and unregulated iron loading. The
      consequences include hepatic fibrosis, cardiomyopathy and skin pigmentation, and
      these sequelae along with fatigue may be prevented by 'de-ironing'. Joint pain is
      frequently reported at diagnosis and an arthropathy that is essentially
      accelerated osteoarthritis may develop, with onset at a younger than expected
      age, involvement of typical and atypical joints, such as metacarpophalangeal and
      ankle, exuberant osteophytes and rapid progression to cartilage loss and the need
      for arthroplasty. The arthropathy differs from the other features in not
      responding to de-ironing, new joints becoming affected once patients are in
      maintenance, and, intriguingly, classic cases occur in the absence of iron
      overload with major and minor HFE mutations. These anomalies present a conundrum
      that raise the question whether HFE mutations have an arthritogenic consequence
      independent of hepcidin and iron.

PMID- 30191912
TI  - Successful intravenous thrombolysis of a wake-up stroke with underlying valvular
      atrial fibrillation.
AB  - A 42-year-old female admitted with new-onset atrial fibrillation had a wake-up
      stroke on the high-dependency unit and the time last seen well (TLSW) was 6.5 h.
      She suffered left-sided body weakness and her National Institutes of Health
      Stroke Scale (NIHSS) score was 17. An emergency CT perfusion showed right M1
      segment occlusion with more than 50% penumbra. She was given recombinant tissue
      plasminogen activator (r-tPA) at 9 h from TLSW. An immediate diagnostic angiogram
      with intention to treat, owing to the presence of large vessel occlusion, showed
      complete reperfusion after intravenous r-tPA. She was discharged with NIHSS of 2,
      and at 3-month follow up her Modified Rankin Scale was 0. We demonstrated a
      successful reperfusion and excellent clinical recovery with intravenous
      thrombolysis in a patient who presented with a wake-up stroke with underlying
      valvular atrial fibrillation despite evidence of large vessel occlusion.

PMID- 30191913
TI  - Possible modulation of concurrent Parkinson's disease in the management of
      metastatic GIST: a review of two cases.
AB  - Imatinib, a tyrosine kinase inhibitor, is the mainstay of treatment for resected
      high-risk (adjuvant and metastatic) gastrointestinal stromal tumour (GIST) - a
      rare form of sarcoma. There has been recent research into the neuroprotective
      role and modulation of dopaminergic neurones by imatinib through the abl pathway
      in Parkinson's disease (PD). We describe two patients from a single cancer centre
      with concurrent diagnoses of PD and metastatic GIST receiving imatinib and
      standard PD management. The cases highlight a potential reduction in PD
      progression using Unified Parkinson's Disease Rating Scale. Further research into
      repurposing of imatinib for PD may provide additional management options for this
      neurodegenerative illness.

PMID- 30191914
TI  - CANTOS - is selective targeting of inflammation in atherosclerosis enough?

PMID- 30191915
TI  - Penetrating aortic ulcer causing intramural haematoma presenting as pericarditis.

PMID- 30191916
TI  - It must be true ... I read it in the tabloids.
AB  - BACKGROUND: Previous attempts to improve the quality of health journalism have
      not led to more responsible reporting of health news. METHOD: We reviewed the
      front pages of three daily tabloid and three daily broadsheet UK newspapers
      during a 1 month period in 2017 for medical headlines in which claims were made
      for diets, lifestyle behaviours or drug therapies that influence health. RESULTS:
      Front page medical headlines were carried by the Daily Express (11), Daily Mail
      (two), Daily Mirror (one) and Daily Telegraph (one). Neither the Guardian nor the
      Independent carried medical stories on their front pages during the period of
      study. Eleven headlines suggested benefits and three suggested harm. One headline
      accurately reflected its source material, but in this instance the source
      material was of doubtful clinical relevance. The remaining 13 headlines either
      exaggerated benefit (seven), exaggerated harm (two) or made false claims (four).
      CONCLUSIONS: The cumulative effect of everyday misreporting of medical stories in
      UK newspapers may not only serve to confuse the public but also have serious
      consequences for public health.

PMID- 30191917
TI  - The last apothecary: Eric Knott (1896-1993) and 20th-century pharmacy in
      Scotland.
AB  - Eric Knott was the last Apothecary at the Royal Public Dispensary and the last
      Principal of the Duncan School of Pharmacy. He linked pre-war apothecary practice
      to post-war chemist dispensing. This paper tracks his career from the Duncan
      School of Pharmacy, transfer to Heriot-Watt College in 1936, to the close of the
      Royal Public Dispensary in 1963, when the premises were transferred to the
      University of Edinburgh. It draws on unpublished archival material and long
      unseen collections from National Museums Scotland to explore what Knott's career
      can tell us about the impact of new legislation and the introduction of the NHS
      on pharmacy in Scotland.

PMID- 30191918
TI  - George Riddoch (1888-1947): the driving force behind the treatment of spinal
      injuries in the UK during the Second World War.
AB  - The development of the successful treatment of spinal injuries has been
      inextricably linked to Sir Ludwig Guttmann and Stoke Mandeville Hospital. The
      role of George Riddoch has largely been ignored or mentioned merely in relation
      to Ludwig Guttmann and his appointment as the first Resident Medical Officer at
      Stoke Mandeville Hospital. Riddoch's contribution was far more significant. New
      material, comprising Riddoch's letters and memoranda written between 1939 and
      1944, reveals his paramount involvement in the setting up of spinal injury units
      across the UK between 1941 and 1944, and his skill as an administrator and a
      clinician. Riddoch must be given credit for finding and appointing Ludwig
      Guttmann.

PMID- 30191919
TI  - Sir Alexander Morison and The Physiognomy of Mental Diseases: Part 1.
AB  - Sir Alexander Morison's The Physiognomy of Mental Diseases and the original art
      work that formed the basis of the book have not had the scholarly attention they
      deserve. The published book and the commissioned portraits have not been studied
      in any detail. Historians have tended to offer cursory assessments that have
      reflected their own preconceived ideas rather than properly engaging with the
      material. This is a pity because Morison's work is a rich source that tells us
      much about the history of psychiatry. The pictures and text give us a glimpse
      into the world of the asylum and that of the patient. Although we see the patient
      through the eyes of the artist and Dr Morison, they do emerge as individuals. The
      accompanying texts reflect the psychiatric approach of the time and reveal
      contemporary notions of diagnosis, aetiology and treatment. Morison's work can
      also be located in the history of ideas about physiognomy. He himself was
      particularly influenced by Jean-Etienne-Dominique Esquirol, and Morison's work,
      in turn, influenced WAF Browne. These papers will outline Morison's career and
      consider in detail his book on The Physiognomy of Mental Diseases.

PMID- 30191920
TI  - Ebola, selective memory and educational costs.

PMID- 30191921
TI  - More on IgG4-related pulmonary disease.

PMID- 30191922
TI  - Author's reply to More on IgG4-related pulmonary disease.

PMID- 30191923
TI  - Treatable alternative causes of extreme hyperferritinaemia.

PMID- 30191924
TI  - Communication through the furan ring: the conformational effect on the internal
      rotation of 5-methyl furfural studied by microwave spectroscopy.
AB  - Internal rotation is a fundamental motion of methyl groups that provides
      important insights into the molecular physics of isolated molecules. The barrier
      heights of such large amplitude motions are highly sensitive to their molecular
      and electronic environment. To date, it is still not possible to accurately
      determine these values using quantum chemical calculations. To probe the effect
      of molecular conformations on the barrier heights of substituted furan rings, the
      molecular jet Fourier transform microwave spectrum of 5-methyl furfural was
      recorded in the frequency range from 2.0 to 40.0 GHz. Quantum chemical
      calculations yielded two conformers with a trans and a cis orientation of the
      formyl group, which were both observed in the experimental spectrum. Torsional
      splittings due to the internal rotation of the methyl group were resolved and
      analyzed. The experimental spectrum is reproduced with standard deviations close
      to the experimental accuracy, yielding sets of highly accurate rotational and
      internal rotation parameters. The results, especially the V3 potentials, are
      compared to quantum chemical calculations and discussed within the scope of the
      current literature of other methyl substituted furans, where the methyl group is
      in close proximity of the furan oxygen atom. The present work provides an
      accurate evaluation of the different case studies and highlights the bottlenecks
      and future options of the currently available theoretical techniques.

PMID- 30191926
TI  - Ab initio molecular dynamics studies of formic acid dimer colliding with liquid
      water.
AB  - Ab initio molecular dynamics simulations of formic acid (FA) dimer colliding with
      liquid water at 300 K have been performed using density functional theory. The
      two energetically lowest FA dimer isomers were collided with a water slab at
      thermal and high kinetic energies up to 68kBT. Our simulations agree with recent
      experimental observations of nearly a complete uptake of gas-phase FA dimer: the
      calculated average kinetic energy of the dimers immediately after collision is 5
      +/- 4% of the incoming kinetic energy, which compares well with the experimental
      value of 10%. Simulations support the experimental observation of no delayed
      desorption of FA dimers following initial adsorption. Our analysis shows that the
      FA dimer forms hydrogen bonds with surface water molecules, where the hydrogen
      bond order depends on the dimer structure, such that the most stable isomer
      possesses fewer FA-water hydrogen bonds than the higher energy isomer.
      Nevertheless, even the most stable isomer can attach to the surface through one
      hydrogen bond despite its reduced hydrophilicity. Our simulations further show
      that the probability of FA dimer dissociation is increased by high collision
      energies, the dimer undergoes isomerization from the higher energy to the lowest
      energy isomer, and concerted double-proton transfer occurs between the FA
      monomers. Interestingly, proton transfer appears to be driven by the release of
      energy arising from such isomerization, which stimulates those internal
      vibrational degrees of freedom that overcome the barrier of a proton transfer.

PMID- 30191925
TI  - Synthesis and molecular structure of pentadienyl complexes of the rare-earth
      metals.
AB  - The coordination chemistry of the sterically encumbered pentadienyl ligand pdl'
      (pdl' = 2,4-(Me3C)2C5H5) towards a series of rare-earth metals was systematically
      explored and the resulting metal complexes were fully characterized by several
      techniques including X-ray diffraction, elemental analysis, NMR spectroscopy and
      solid-state magnetic susceptibility studies. Three different reaction products
      were isolated depending on the redox-potentials and ionic radii of the metal
      atoms. They can be classified as (a) salt-metathesis, (b) metal reduction-ligand
      oxidation and (c) ligand deprotonation products. While for the larger and
      difficult to reduce metal ions, M = La, Ce, Pr and Nd, trivalent compounds [(eta5
      pdl')3M] (1-M) were isolated, for the more readily reduced metal ions the
      corresponding divalent compounds [[(eta5-pdl')2M(thf)n] (2-M; with M = Sm (n =
      2); Eu, Yb (n = 1)) were formed. A more complex structural motif was observed for
      the smaller and also difficult to reduce metal ions, M = Sc, Y, Gd, Tb, Dy, Ho,
      Er, Tm and Lu, which yielded the bimetallic complexes of the type [(pdl')(pdl'
      1H)(pdl'-2H)M2(thf)2] (3-M). In these dimeric complexes the pdl' ligand acts as a
      result of deprotonation reactions not only as a monoanionic [pdl']-, but also as
      a dianionic [pdl'-1H]2- and a trianionic [pdl'-2H]3- ligand scaffold, which form
      unusual structural motifs including a six-membered metallacycle. Solid-state
      magnetic susceptibility studies revealed the expected free-ion magnetic moments
      at T = 300 K for all investigated compounds, whereas at lower temperatures
      crystal-field effects dominate. Furthermore, for 3-Gd, 3-Tb, 3-Dy and 3-Er weak
      ferromagnetic exchange interactions were observed at low temperature.

PMID- 30191927
TI  - Atomically-defined model catalysts in ultrahigh vacuum and in liquid
      electrolytes: particle size-dependent CO adsorption on Pt nanoparticles on
      ordered Co3O4(111) films.
AB  - We have studied particle size effects on atomically-defined model catalysts both
      in ultrahigh vacuum (UHV) and under electrochemical (EC) conditions in liquid
      electrolytes. The model catalysts were prepared in UHV by physical vapour
      deposition (PVD) of Pt onto an ordered Co3O4(111) film on Ir(100), yielding
      nanoparticles (NPs) with an average size from 10 to 500 atoms per particle (0.8
      to 3 nm). The model systems were characterized in UHV using surface science
      methods including scanning tunnelling microscopy (STM), before transferring them
      out of the UHV and into the electrolyte without contact to ambient conditions. By
      X-ray photoelectron spectroscopy (XPS) we show that the model surfaces are stable
      in the EC environment under the applied conditions (0.1 to 1 M phosphate buffer,
      pH 10, 0.33 to 1.03 VRHE). As a reference, we study Pt(111) under identical
      conditions. In UHV, we also investigated the adsorption of CO using infrared
      reflection absorption spectroscopy (IRRAS). Under EC conditions, we performed
      equivalent experiments using EC infrared reflection absorption spectroscopy (EC
      IRRAS) in combination with cyclic voltammetry (CV). Characteristic differences
      were observed between the IR spectra under EC conditions and in UHV. Besides the
      red-shift induced by the interfacial electric field (Stark effect), the EC IR
      bands of CO on Pt(111) show a larger width (by a factor of 2) as a result of
      local variations in the CO environment and coupling to the electrolyte. The CO IR
      bands of the Pt NPs are even broader (by a factor of 5), which is attributed to
      local variations of the interfacial electric field at the NP surface. Further
      pronounced differences are observed between the spectra taken in UHV and in the
      electrolyte regarding the site occupation and its dependence on particle size. In
      UHV, adsorption at on-top sites is preferred on Pt(111) at low coverage and
      similar adsorption ratios of on-top and bridge-bonded CO are formed at saturation
      coverage. In sharp contrast, on-top adsorption of CO on Pt(111) is partially
      suppressed under EC conditions. This effect is attributed to the competitive
      adsorption of anions from the electrolyte and leads to a clear preference for
      bridge sites at higher potentials (>0.5 VRHE). For the Pt NPs, the situation is
      different and an increasing fraction of on-top CO is observed with decreasing
      particle size, both under EC conditions and in UHV. For the smallest particles
      (10-20 atoms) we do not detect any bridge-bonded CO. This change in site
      preference as a function of particle size is attributed to stronger on-top
      adsorption on low-coordinated Pt atoms of small Pt NPs. The effect leads to a
      clear preference for on-top adsorption in the electrolyte even at low CO coverage
      and over the full potential range studied.

PMID- 30191928
TI  - Dispersion-aggregation-dispersion colorimetric detection for mercury ions based
      on an assembly of gold nanoparticles and carbon nanodots.
AB  - Mercury is a common heavy metal element in natural systems and is highly toxic to
      the human body. Herein, a novel colorimetric detection of Hg2+ ions is proposed
      based on the aggregation of gold nanoparticles (AuNPs) induced by carbon quantum
      dots (CDs) with the assistance of glutathione (GSH). In this sensing system, the
      AuNP/CDs composite forms through Au-N bonds. Simultaneously, the color of the
      solution turns from wine red to blue. The well-dispersed AuNPs can be restored
      after the addition of GSH, because GSH competes with CDs to bind onto the surface
      of AuNPs and protect AuNPs from aggregation. In the presence of Hg2+ ions, GSH
      can chelate with Hg2+ to form a complex, which subsequently enables CDs to
      facilitate the aggregation of the AuNPs again. Therefore, according to the red-to
      blue color change, a colorimetric sensor is established for the sensitive and
      selective detection of Hg2+ with a detection limit of 7.5 nM. Moreover, this
      sensor is successfully used to detect Hg2+ spiked in environmental water. This
      very simple and cost-effective strategy will promote the development of a
      colorimetric sensor for the determination of other metal ions in biological and
      environmental fields.

PMID- 30191929
TI  - Fluorine-18: an untapped resource in inorganic chemistry.
AB  - Advances in the field of fluorine chemistry have been applied extensively to the
      syntheses of 18F-labelled organic compounds and radiopharmaceuticals. However,
      18F has sparely been used as a tool to explore inorganic chemistry and can be
      viewed as a research area worthy of further development. This review highlights
      the application of 18F in development of inorganic fluorinating agents,
      mechanistic studies and imaging tools.

PMID- 30191930
TI  - Reduction of PCE and TCE by magnetite revisited.
AB  - Here we revisit whether the common mixed-valent Fe mineral, magnetite, is a
      viable reductant for the abiotic natural attenuation of perchloroethylene (PCE)
      and trichloroethylene (TCE) in anoxic groundwater plumes. We measured PCE and TCE
      reduction by stoichiometric magnetite as a function of pH and Fe(ii)
      concentration. In the absence of added Fe(ii), stoichiometric magnetite does not
      reduce PCE and TCE over a three month period under anoxic conditions. When Fe(ii)
      is added to magnetite suspensions, PCE and TCE are reduced under Fe(ii) and pH
      conditions that appear to be controlled by the solubility of ferrous hydroxide,
      Fe(OH)2(s). Reduction rates are slow with only 1 to 30% carbon products
      (primarily acetylene) accumulating over several months. We conducted a similar
      set of experiments with Fe(OH)2(s) alone and found that, compared to in the
      presence of magnetite, Fe(OH)2(s) reduces PCE and TCE only at Fe(ii)
      concentrations that are too high (>=13 mM, 726 mg L-1) to be representative of
      natural aquifer conditions. Our results suggest that magnetite present in aquifer
      sediments alone is unlikely to reduce PCE and TCE sufficiently fast to contribute
      to natural attenuation of PCE and TCE. The lack of compelling evidence for PCE
      and TCE reduction by magnetite raises important questions regarding the current
      application of using magnetic susceptibility as a potential indicator for abiotic
      natural attenuation. Dynamic conditions and high Fe(ii) concentrations that favor
      active precipitation of minerals, such as Fe(OH)2(s) in the presence of magnetite
      (or other Fe minerals), however, may lead to PCE and TCE reduction that could
      help attenuate PCE and TCE plumes.

PMID- 30191931
TI  - Photochromic and luminescence properties of a hybrid compound based on indoline
      spiropyran of the coumarin type and azomethinocoumarin.
AB  - A novel hybrid compound whose molecule includes the photochromic spiropyran
      fragment and two fluorophores - coumarin and salicylideneimine - was synthesized
      by the reaction of two equivalents of 8-formyl-7-hydroxy-4-methylcoumarin with 5
      amino-1,3,3-trimethyl-2-methyleneindoline. Its spectral-kinetic and fluorescence
      properties were studied in comparison with model compounds - 7-hydroxy-4-methyl
      coumarin, spiropyran of the coumarin type, and azomethinocoumarin in toluene and
      ethanol. It was shown that the hybrid compound exhibited photochromic
      transformations in both solvents. Different fluorescence emissions of the initial
      spirocycle and UV irradiation-induced merocyanine forms were observed. One green
      fluorescence emission with a maximum at 545 nm was observed for the initial
      closed form in toluene, and several emissions with maxima at 390 nm, 440 nm, 450
      nm (violet), and 530 nm (green) appeared in ethanol. An additional red emission
      of the open merocyanine form in the region of 665 nm appeared after UV
      irradiation in both solvents. Reversible modulation of fluorescence in both the
      initial and photoinduced merocyanine forms in the process of photochromic
      transformations was discovered. It was shown that the fluorescence modulation of
      the hybrid compound in weakly polar toluene was caused by resonance energy
      transfer from the fluorescent fragment of the photochromic compound to the
      photoinduced merocyanine form, leading to the process of photochromic
      transformations. Reversible modulation of fluorescence in ethanol solutions was
      achieved through a photoinduced change in the ratio of the concentrations of
      conformers.

PMID- 30191932
TI  - Unusual anti-inflammatory meroterpenoids from the marine sponge Dactylospongia
      sp.
AB  - Five new sesquiterpene hydroquinones, dactylospongins A-D (1-4) and 19-O
      methylpelorol (10), as well as four new sesquiterpene quinones, melemeleones C-E
      (6-8) and dysidaminone N (9), were isolated from the marine sponge Dactylospongia
      sp. collected from the South China Sea, along with five known analogues, ent
      melemeleone B (5), pelorol (11), 17-O-acetylavarol (12), 20-O-acetylavarol (13),
      and 20-O-acetylneoavarol (14). The structures were elucidated by spectroscopic
      data analyses and comparison with the published NMR data, while the absolute
      configurations of new structures were assigned by comparison between the
      experimental and calculated ECD spectra. Dactylospongins A (1) and B (2) are the
      first sesquiterpenoids with a benzothiazole ring from the marine environment.
      Anti-inflammatory evaluation showed that 1, 2, 4, 5, 9, and 10 showed potent
      inhibitory effects on the production of inflammatory cytokines (IL-6, IL-1beta,
      IL-8, and PEG2) in LPS-induced THP-1 cells with IC50 values of 5.1-9.2 MUM;
      however, none of them showed significant effects on the production of MCP-1 and
      TNF-alpha. Additionally, 19-O-methylpelorol (10) exhibited cytotoxicity against
      lung cancer PC-9 cell lines with an IC50 value of 9.2 MUM.

PMID- 30191933
TI  - Experimental evidence for the formation of cationic intermediates during
      iodine(iii)-mediated oxidative dearomatization of phenols.
AB  - Iodine(iii)-based oxidants are commonly used reagents for the oxidative
      dearomatization of phenols. Having a better understanding of the mechanism
      through which these reactions proceed is important for designing new iodine(iii)
      based reagents, catalysts, and reactions. We have performed a Hammett analysis of
      the oxidative dearomatization of substituted 4-phenylphenols. This study confirms
      that iodine(iii)-mediated oxidative dearomatizations likely proceed through
      cationic phenoxenium ions and not the direct addition of a nucleophile to an
      iodine-bound phenol intermediate.

PMID- 30191934
TI  - An integrated nanocatalyst combining enzymatic and metal-organic framework
      catalysts for cascade degradation of organophosphate nerve agents.
AB  - An integrated nanocatalyst (INC), denoted OPH@MIL-100(Fe), was synthesized by
      immobilizing a biocatalyst onto a metal-organic framework (MOF)-based catalyst,
      which can cascadingly degrade organophosphate nerve agents to 4-aminophenol (4
      AP) and result in a sharp decrease of their toxicity up to 208-fold.

PMID- 30191935
TI  - Primer dephosphorylation-initiated circular exponential amplification for
      ultrasensitive detection of alkaline phosphatase.
AB  - Alkaline phosphatase (ALP) is an important diagnostic indicator for various human
      diseases including bone diseases, liver dysfunction, diabetes, breast and
      prostatic cancers. However, the conventional methods for ALP assay are usually
      cumbersome and time-consuming with low sensitivity. Here, we develop a new
      fluorescent method for ultrasensitive detection of ALP activity on the basis of
      primer dephosphorylation-initiated isothermal circular exponential amplification.
      We design two dual-functional hairpin probes (HP1 and HP2), which function as
      both the templates for exponential amplification reaction (EXPAR) and the
      generators for signal output. In the presence of ALP, the 3'-phosphorylated
      primer is dephosphorylated and subsequently hybridizes with the 3' protruding end
      of HP1 to initiate the first strand displacement amplification (SDA), producing
      trigger 1 and fluorescence signal. The released trigger 1 is complementary to the
      3' protruding end of HP2 for the initiation of the second SDA, producing trigger
      2 and fluorescence signal. Notably, trigger 2 is complementary to the 3'
      protruding end of HP1 and may subsequently initiate two consecutive SDAs,
      enabling circular EXPAR to generate an amplified fluorescence signal. This method
      exhibits high sensitivity with a detection limit of 2.0 * 10-10 U MUL-1 and a
      large dynamic range of 5 orders of magnitude from 1.0 * 10-9 to 1.0 * 10-4 U MUL
      1, and it can measure ALP at the single-cell level. Importantly, this method can
      be applied for the measurement of kinetic parameters and the screening of
      potential inhibitors, providing a powerful tool for ALP-related biomedical
      research and clinical diagnosis.

PMID- 30191936
TI  - Shifted equilibria of organic acids and bases in the aqueous surface region.
AB  - Acid-base equilibria of carboxylic acids and alkyl amines in the aqueous surface
      region were studied using surface-sensitive X-ray photoelectron spectroscopy and
      molecular dynamics simulations. Solutions of these organic compounds were
      examined as a function of pH, concentration and chain length to investigate the
      distribution of acid and base form in the surface region as compared to the
      aqueous bulk. Results from these experiments show that the neutral forms of the
      studied acid-base pairs are strongly enriched in the aqueous surface region.
      Moreover, we show that for species with at least four carbon atoms in their alkyl
      chain, their charged forms are also found to be abundant in the surface region.
      Using a combination of XPS and MD results, a model is proposed that effectively
      describes the surface composition. Resulting absolute surface concentration
      estimations show clearly that the total organic mole fractions in the surface
      region change drastically as a function of solution pH. The origin of the
      observed surface phenomena, hydronium/hydroxide concentrations in the aqueous
      surface region and why standard chemical equations, used to describe equilibria
      in dilute bulk solution are not valid in the aqueous surface region, are
      discussed in detail. The reported results are of considerable importance
      especially for the detailed understanding of properties of small aqueous droplets
      that can be found in the atmosphere.

PMID- 30191937
TI  - Role of Stefan-Maxwell fluxes in the dynamics of concentrated electrolytes.
AB  - This theoretical analysis quantifies the effect of coupled ionic fluxes on the
      charging dynamics of an electrochemical cell. We consider a model cell consisting
      of a concentrated, binary electrolyte between parallel, blocking electrodes,
      under a suddenly applied DC voltage. It is assumed that the magnitude of the
      applied voltage is small compared to the thermal voltage scale, RT/F, where R is
      the universal gas constant, T is the temperature and F is the Faraday's constant.
      We employ the Stefan-Maxwell equations to describe the hydrodynamic coupling of
      ionic fluxes that arise in concentrated electrolytes. These equations inherently
      account for asymmetry in the mobilities of the ions in the electrolyte. A
      modified set of Poisson-Nernst-Planck equations, obtained by incorporating Stefan
      Maxwell fluxes into the species balances, are formulated and solved in the limit
      of weak applied voltages. A long-time asymptotic analysis reveals that the
      electrolyte dynamics occur on two distinct time scales. The first is a faster
      "RC" time, tauRC = kappa-1L/DE, where kappa-1 is the Debye length, L is the
      length of the half-cell, and DE is an effective diffusivity, which characterizes
      the evolution of charge density at the electrode. The effective diffusivity, DE,
      is a function of the ambi-polar diffusivity of the salt, Da, as well as a cross
      diffusivity, D+-, of the ions. This time scale also dictates the initial
      exponential decay of current in the external circuit. At times longer than tauRC,
      the external current again decays exponentially on a slower, diffusive time
      scale, tauD~L2/Da, where Da is the ambi-polar diffusivity of the salt. This
      diffusive time scale is due to the unequal ion mobilities that result in a non
      uniform bulk concentration of the salt during the charging process. Finally, we
      propose an approach by which our theory may be used to measure the cross
      diffusivity in concentrated electrolytes.

PMID- 30191938
TI  - The importance of N-heterocyclic carbene basicity in organocatalysis.
AB  - N-Heterocyclic carbenes (NHCs) are versatile species that figure prominently as
      catalysts. Despite their widespread use in organocatalysis, studies of the
      relationship between the basicity of NHCs and their catalytic ability are
      limited. Herein we review work on both the examination of NHC basicity as well as
      its impact on organocatalysis. The review is divided into three main parts: an
      overview of NHC basicity studies, both in solution and in the gas phase; the role
      of basicity in Umpolung-type catalysis; and the relationship between NHC basicity
      and its growing role as a Bronsted base catalyst. This review is not an
      exhaustive catalog of all NHC catalysis, but rather focuses on work that
      specifically examines and discusses the effect of NHC basicity on catalyst
      function.

PMID- 30191939
TI  - Laser-induced remote release in vivo in C. elegans from novel silver
      nanoparticles-alginate hydrogel shells.
AB  - Non-destructive, controllable, remote light-induced release inside cells enables
      studying time- and space-specific processes in biology. In this work we
      demonstrate the remote release of tagged proteins in Caenorhabditis elegans (C.
      elegans) worms using a near-infrared laser light as a trigger from novel hydrogel
      shells functionalized with silver nanoparticles responsive to laser light. A new
      type of hydrogel shells was developed capable of withstanding prolonged storage
      in the lyophilized state to enable the uptake of the shell by worms, which takes
      place on an agar plate under standard culture conditions. Uptake of the shells by
      C. elegans was confirmed using confocal laser scanning microscopy, while release
      from alginate shells in C. elegans and the laser effect on the shells on a
      substrate in air was followed using fluorescence microscopy. In addition, Raman
      microscopy was used to track the localization of particles to avoid the influence
      of autofluorescence. Hierarchical cluster spectral analysis is used to extract
      information about the biochemical composition of an area of a nematode containing
      the hydrogel shells, whose Raman signal is enhanced by the SERS (Surface Enhanced
      Raman Scattering) effect due to hot spots formed by silver nanoparticles present
      in the shells. The in vivo release demonstrated here can be used to study
      intestinal microbiota and probiotic compounds as well as a possible future
      strategy for gene delivery in the worms, other insects and other organisms.

PMID- 30191940
TI  - Biosynthesis and chemical diversity of beta-lactone natural products.
AB  - Covering: up to 2018beta-Lactones are strained rings that are useful organic
      synthons and pharmaceutical warheads. Over 30 core scaffolds of beta-lactone
      natural products have been described to date, many with potent bioactivity
      against bacteria, fungi, or human cancer cell lines. beta-Lactone natural
      products are chemically diverse and have high clinical potential, but production
      of derivatized drug leads has been largely restricted to chemical synthesis
      partly due to gaps in biochemical knowledge about beta-lactone biosynthesis. Here
      we review recent discoveries in enzymatic beta-lactone ring closure via ATP
      dependent synthetases, intramolecular cyclization from seven-membered rings, and
      thioesterase-mediated cyclization during release from nonribosomal peptide
      synthetase assembly lines. We also comprehensively cover the diversity and
      taxonomy of source organisms for beta-lactone natural products including their
      isolation from bacteria, fungi, plants, insects, and marine sponges. This work
      identifies computational and experimental bottlenecks and highlights future
      directions for genome-based discovery of biosynthetic gene clusters that may
      produce novel compounds with beta-lactone rings.

PMID- 30191941
TI  - Anisotropic contraction of fiber-reinforced hydrogels.
AB  - Hydrogels reinforced by fibers can undergo remarkable anisotropic contraction
      triggered by external stimuli, which has a broad appeal for various applications.
      However, little is known about how to optimize the contraction anisotropy by
      tuning the microstructures of fiber-reinforced hydrogels. Here, we investigate
      the underlying mechanisms controlling the anisotropic contraction of fiber
      reinforced hydrogels. Using a simplified model incorporating the directional
      constraint of the fibers, we show that the contraction anisotropy can be
      substantially enhanced if the hydrogel is prestretched along the fiber direction.
      We further explicitly model fibers as periodically distributed cylindrical rods
      in the finite element simulations, and find that the contraction anisotropy can
      be maximized by varying the transverse fiber-fiber distance; this maximum
      anisotropy can be improved by reducing the longitudinal fiber-fiber distance and
      increasing the fiber length. Our study provides insights into designing novel
      fiber-reinforced hydrogels, suggesting possible applications in soft robotics,
      tissue engineering and beyond.

PMID- 30191942
TI  - In silico identification and characterization of sensory motifs in the
      transcriptional regulators of the ArsR-SmtB family.
AB  - The ArsR-SmtB family of proteins displays the greatest diversity among the
      bacterial metal-binding transcriptional regulators with regard to the variety of
      metal ions that they can sense. In the presence of increased levels of toxic
      heavy metals, these proteins dissociate from their cognate DNA upon the direct
      binding of metal ions to the appropriate sites, designated motifs on the
      proteins, either at the interface of the dimers or at the intra-subunit
      locations. In addition to the metal-mediated regulation, some proteins were also
      found to control transcription via redox reactions. In the present work, we have
      identified several new sequence motifs and expanded the knowledge base of metal
      binding sites in the ArsR-SmtB family of transcriptional repressors, and
      characterized them in terms of the ligands to the metal, distribution among
      different phyla of bacteria and archaea, amino acid propensities, protein length
      distributions and evolutionary interrelationships. We built structural models of
      the motifs to show the importance of specific residues in an individual motif.
      The wide abundance of these motifs in sequences of bacteria and archaea indicates
      the importance of these regulators in combating metal-toxicity within and outside
      of the hosts. We also show that by using residue composition, one can distinguish
      the ArsR-SmtB proteins from other metalloregulatory families. In addition, we
      show the importance of horizontal gene transfer in microorganisms, residing in
      similar habitats, on the evolution of the structural motifs in the family.
      Knowledge of the diverse metalloregulatory systems in microorganisms could enable
      us to manipulate specific genes that may result in a toxic metal-free
      environment.

PMID- 30191944
TI  - Organometallic and coordination chemistry of the s-block metals.

PMID- 30191943
TI  - Self-assembly of folic acid dextran conjugates for cancer chemotherapy.
AB  - Folic acid (FA) has long been used as a specific targeting agent since many
      cancer cells overexpress folate receptors (FRs). Herein, novel functionalities of
      FA will be explored: directed self-assembly of nanoparticles for drug delivery
      together with pH responsive release. By conjugating with dextran (DEX), DEX-FA
      exerts a pH dependent self-assembly behavior: it self-associates into
      nanoparticles (NPs) around physiological pH (pH 7) and disassembles at higher pH
      (pH > 9). Doxorubicin (DOX), a model antitumor drug, has been successfully
      encapsulated via electrostatic interactions between DOX and FA. Moreover, the pH
      responsive release behaviors of DOX are controlled by FA. The DOX@DEX-FA NPs
      exhibit typical FA-FRs-mediated endocytosis in vitro and targeted delivery in
      vivo, altogether contributing to an enhanced antitumor efficacy, alleviated side
      effects, and elongated overall survival in a 4T1 subcutaneous tumor-bearing mouse
      model. The DOX@DEX-FA NPs have been demonstrated to be a simple, safe and
      efficient nanoplatform, holding significant translation potential for treating FR
      overexpressing cancers. This study may present novel functionalities of FA in
      cancer-targeted nanotherapeutics.

PMID- 30191945
TI  - Artificial lithium fluoride surface coating on silicon negative electrodes for
      the inhibition of electrolyte decomposition in lithium-ion batteries:
      visualization of a solid electrolyte interphase using in situ AFM.
AB  - The solid electrolyte interphase (SEI), which is a surface layer formed on the
      negative electrode, plays an important role in inhibiting the reductive
      decomposition of the electrolyte solution in a lithium-ion battery. However, it
      has not been understood well which components are important for the SEI to
      prevent the electrolyte decomposition. Lithium fluoride (LiF), as an artificial
      SEI, was formed on an amorphous-Si thin film by physical vapor deposition.
      Changes in the surface morphology of the Si electrode with potential sweeping
      were investigated using in situ atomic force microscopy (AFM). Although large
      amounts of non-uniform surface deposits that originate from electrolyte
      decomposition emerged on the bare Si-film electrode during the first lithiation
      process, few surface deposits were observed on the LiF-coated Si-film electrode
      even after two cycles in an ethylene carbonate-based electrolyte solution without
      additives. It is clear that LiF is a required SEI component that inhibits
      electrolyte decomposition on Si negative electrodes.

PMID- 30191946
TI  - To study surface and sub-surface nanomechanical properties of electrospun
      polyacrylonitrile (PAN) nanofibers/polydimethylsiloxane (PDMS) composites.
AB  - We investigate surface and sub-surface nanomechanical properties of
      nanocomposites based on a crosslinked polydimethylsiloxane (PDMS) elastomer and
      electrospun polyacrylonitrile (PAN) nanofibers. Fabrication of PDMS substrates
      with anisotropy with respect to surface elasticity and their characterization in
      terms of local nanomechanical properties are important for many areas of adhesion
      applications. PDMS nanocomposite substrates with variations in surface elasticity
      over large areas are prepared by controllably embedding electrospun PAN
      nanofibers (~600 nm) in a PDMS matrix using the solution casting technique.
      Variations of local surface stiffness properties of prepared composites are
      measured using force spectroscopy and force mapping modes of atomic force
      microscopy and compared with their macroscopic (bulk) mechanical properties.
      Since the surface of the prepared nanocomposite is elastically non-homogeneous,
      our studies are mainly focused on the investigation of the hysteresis (plasticity
      index) between loading and unloading curves which is a measure of energy
      dissipation in AFM indentation experiments. The distribution of the local
      plasticity index in the PAN/PDMS composites is related to the specific
      organization of electrospun nanofibers at the surface and sub-surface layers of
      the PDMS matrix. We observed that embedding 0.1-1% PAN nanofibers induces anti
      plasticization effects for lower (0.1%) and higher (1%) concentrations of PAN
      nanofibers which represent the formation of interpenetrating networks and mat
      like blended structures of PAN nanofibers within the PDMS matrix.

PMID- 30191947
TI  - Expression of glutamine metabolism-related proteins in Hurthle cell neoplasm of
      thyroid: Comparison with follicular neoplasm.
AB  - PURPOSE: We evaluated the expression of glutaminolysis-related proteins in
      Hurthle cell neoplasms (HCN) and follicular neoplasms (FN) of the thyroid, and
      investigated its clinical implication. METHODS: Tissue microarrays were
      constructed from 264 FNs (112 follicular carcinomas [FCs] and 152 follicular
      adenomas [FAs]) and 108 HCNs (27 Hurthle cell carcinomas [HCCs] and 81 Hurthle
      cell adenomas [HCAs]. The immunohistochemical staining result of 3 glutaminolysis
      related proteins (Glutaminase 1 [GLS1], glutaminate dehydrogenase [GDH] and
      alanine- serine, cysteine-preferring transporter 2 [ASCT2]) was analyzed.
      RESULTS: GLS1 and GDH showed significantly higher expression rates in HCN
      compared to FN (P<0.001). More HCN cases showed co-positivity of multiple
      glutaminolysis-related proteins than those of FN cases (P<0.001). In silico
      analysis, both GLUD1 and GLUD2 showed higher expression rate in HCA compared to
      FA (P=0.027 and P=0.018, respectively). SLC1A5 expression was highest in HCA,
      followed by FC and FA (HCA vs FC, P=0.023; FC vs FA, P=0.002). CONCLUSION: FN and
      HCN exhibit a different expression pattern for glutaminolysis-related proteins,
      and GLS1 and GDH have higher expression rates in HCN and FN.

PMID- 30191948
TI  - MicroRNA-384-3p inhibits retinal neovascularization through targeting hexokinase
      2 in mice with diabetic retinopathy.
AB  - Diabetic retinopathy (DR) presents a microvascular complication of diabetes,
      which may contribute to visual impairment. The treatment of DR is still
      controversial. Accumulating studies have reported the role of microRNAs (miRs) in
      DR. This study aims to explore the functions of microRNA-384-3p (miR-384-3p) in
      retinal neovascularization by targeting hexokinase 2 (HK2) in mice with DR. A
      total of 43 C57BL/6 male mice were selected and divided into normal ( n = 16) and
      DR ( n = 27) groups. Retinal microvascular endothelial cells (RMECs) were
      collected from the normal and DR mice and mainly treated with a miR-384-3p mimic,
      a miR-384-3p inhibitor, small interfering RNA (siRNA) against HK2 and HK2
      overexpression plasmids to understand the underlying regulatory mechanisms of miR
      384-3p. The relationship between miR-384-3p and HK2 was determined by dual
      luciferase reporter assay. The miR-384-3p expression and the mRNA and the protein
      expressions of HK2 and CD31 in retinal tissues and cells were evaluated using
      reverse transcription quantitative polymerase chain reaction (RT-qPCR) and
      western blot assay. Cell proliferation was assessed by 3-(4,5-dimethylthiazol-2
      yl)-2,5-diphenyltetrazolium bromide assay. Tube formation was observed by
      conducting a tube formation experiment. HK2 is a target gene of miR-384-3p. The
      DR mice showed higher expression of HK2 and CD31 but lower expression of miR-384
      3p. The miR-384-3p mimic and siRNA-HK2 reduced the expression of HK2, decreased
      cell proliferation and tube formation of RMECs, whereas the miR-384-3p inhibitor
      could reverse these trends. Our study demonstrates that overexpression of miR-384
      3p inhibits retinal neovascularization in DR mice via inhibition of HK2.

PMID- 30191949
TI  - MicroRNA-590-5p functions as a tumor suppressor in breast cancer conferring
      inhibitory effects on cell migration, invasion, and epithelial-mesenchymal
      transition by downregulating the Wnt-beta-catenin signaling pathway.
AB  - Breast cancer remains one of the foremost primary causes of female morbidity and
      mortality worldwide. During the current study, the effect of miR-590-5p and
      paired-like homeodomain transcription factor 2 (PITX2) on proliferation,
      invasion, migration, and epithelial-mesenchymal transition (EMT) of human breast
      cancer via the Wnt-beta-catenin signaling pathway was investigated. Breast cancer
      related genes and related signaling pathways were obtained from KEGG database.
      The PITX2 regulatory microRNA was predicted. To define the contributory role by
      which miR-590-5p influences the progression of breast cancer, the interaction
      between miR-590-5p and PITX2 was explored; the proliferation, invasion, and
      migration abilities as well as the tumor growth and metastasis in nude mice were
      detected following the overexpression or silencing of miR-590-5p. PITX2 was
      determined to share a correlation with breast cancer and miR-590-5p was selected
      for further analysis. PITX2, Wnt-1, beta-catenin, N-cadherin, and vimentin all
      displayed higher levels, while miR-590-5p and E-cadherin expression were lower
      among breast cancer tissues than in the adjacent normal tissue. After
      overexpression of miR-590-5p or si-PITX2, the expression of E-cadherin was
      markedly increased, decreases in the expression of Wnt-1, beta-catenin, N
      cadherin, and vimentin, as well as inhibited cell proliferation, invasion,
      migration, metastasis, and EMT were observed. This study provides evidence
      suggesting that the transfection of overexpressed miR-590-5p can act to alleviate
      the effects of breast cancer demonstrating an ability to inhibit the processes of
      cell proliferation, migration, and invasion as well as EMT by suppressing the
      expression of PITX2 and activation of the Wnt-beta-catenin pathway.

PMID- 30191950
TI  - A novel SOCS5/miR-18/miR-25 axis promotes tumorigenesis in liver cancer.
AB  - The role of miRNAs with tumor suppressive activity in liver cancer has been well
      studied. However, little is known about potential oncomiRs in HCC. In our study,
      we conducted a systematic evaluation of candidate oncomiRs and found that
      upregulation of miR-18a and miR-25 in HCC was associated with poor patient
      survival and promoted proliferation in HCC cell lines. These two miRNAs belong to
      the polycistronic paralogous miR-17-92 and miR-25-106b clusters respectively.
      Although the members of both clusters are often upregulated in HCC, the
      contribution of individual miRNAs in these clusters to HCC tumorigenesis is not
      fully understood. We validated SOCS5 as a bona fide target of both miRNAs, and
      established, for the first time, the tumor suppressive role of SOCS5 in liver
      cancer. We further investigated the mechanism by which SOCS5 contributes to
      tumorigenesis, demonstrated that this SOCS5/miR-18a/miR-25 axis regulates the
      tumor suppressor TSC1 and downstream mTOR signaling, and highlighted the
      potential therapeutic use of miR-18a and miR-25 inhibition in restoring SOCS5
      levels in HCC.

PMID- 30191951
TI  - Diagnosing intellectual disability: detecting big concerns with small
      instruments.

PMID- 30191952
TI  - Families' and health care professionals' attitudes towards Li-Fraumeni syndrome
      testing in children: A systematic review.
AB  - Li-Fraumeni syndrome (LFS) is a highly penetrant cancer predisposition syndrome
      caused by germline TP53 mutations. Genetic testing is not routinely offered in
      asymptomatic children at risk of the condition as the benefits are debatable and
      the attitudes of families and health care professionals (HCPs) may vary. This
      review assessed the attitudes of families and HCPs towards offering genetic
      testing to children for LFS, with a focus on perceived advantages and
      disadvantages and involvement of children in the decision-making process. We
      searched three key databases (Medline, PsycINFO and EMBASE) to identify
      quantitative and qualitative studies. We screened 729 articles identifying eight
      studies for detailed review. Most parents perceived TP53 genetic testing to be
      beneficial in childhood, despite previous lack of surveillance guidelines.
      Parents raised some concerns, including decreased insurability and diminishing
      the child's autonomy. Most children tested reported no negative emotional
      concerns after testing, even if tested positive. Despite generally positive
      interest clinicians remain hesitant. Most families saw the value in involving
      children in decision-making. Families' acceptance of TP53 testing in childhood
      was high. This review highlights the need for research on the long-term
      psychosocial impacts of testing and the attitudes of families to be reflected in
      professional guidelines.

PMID- 30191953
TI  - Vitamin C counteracts miR-302/367-induced reprogramming of human breast cancer
      cells and restores their invasive and proliferative capacity.
AB  - Epigenetic reprogramming by embryonic stem cell-specific miR-302/367 cluster has
      shown some tumor suppressive effects in cancer cells of different tissues such as
      skin, colon, and cervix. Vitamin C has been known as a reprogramming enhancer of
      human and mouse somatic cells. In this study, first we aimed to investigate
      whether exogenous induction of miR-302/367 in breast cancer cells shows the same
      tumor suppressive effects previously observed in other cancer cells lines, and
      whether vitamin C can enhance reprogramming of breast cancer cells and also
      improve the tumor suppressive function of miR-302/367 cluster. Overexpression of
      miR-302/367 cluster in MDA-MB-231 and SK-BR-3 breast cancer cells upregulated
      expression of miR-302/367 members and also some core pluripotency factors
      including OCT4A, SOX2 and NANOG, induced mesenchymal to epithelial transition,
      suppressed invasion, proliferation, and induced apoptosis in the both cell lines.
      However, treatment of the miR-302/367 transfected cells with vitamin C suppressed
      the expression of pluripotency factors and augmented the tumorigenicity of the
      breast cancer cells by restoring their proliferative and invasive capacity and
      compromising the apoptotic effect of miR-302/367. Supplementing the culture
      medium with vitamin C downregulated expression of TET1 gene which seems to be the
      reason behind the negative impact of vitamin C on the reprogramming efficiency of
      miR-302/367 cluster and its anti-tumor effects. Therefore application of vitamin
      C may not always serve as a reprogramming enhancer depending on its switching
      function on TET1. This phenomenon should be carefully considered when considering
      a reprogramming strategy for tumor suppression.

PMID- 30191954
TI  - Therapeutic potency of Wnt signaling antagonists in the pathogenesis of prostate
      cancer, current status and perspectives.
AB  - Prostate cancer is a major cause of cancer-related death in males. Wnt/beta
      catenin signaling plays a critical role in the pathogenesis of this disease by
      regulating angiogenesis, drug resistance, cell proliferation, and apoptosis.
      Suppression of Wnt canonical or noncanonical signaling pathways via Wnt
      biological or pharmacological antagonists is a potentially novel therapeutic
      approach for patients with prostate cancer. This review summarizes the role of
      Wnt signaling inhibitors in the pathogenesis of prostate cancer for a better
      understanding and hence a better management of this disease.

PMID- 30191955
TI  - Association of polymorphisms in genes coding for antioxidant enzymes and human
      male infertility.
AB  - PURPOSE: Although oxidative stress is thought to be an important cause of male
      infertility, primarily due to DNA and cell membrane damage, little is known about
      the genetic causes underlying suboptimal function of the seminal enzymatic
      antioxidant system. The aim of this study was to investigate the relationship of
      four potentially functional polymorphisms associated with oxidative stress
      pathway genes (superoxide dismutase-SOD2 lle58Thr and SOD2 rs4880, catalase-CAT C
      262T, glutathione peroxidase 1-GPX1 Pro200Leu) and two null variants of the
      glutathione S transferase (GSTT and GSTM) genes and infertility risk. METHODS: A
      case control study was conducted on 313 infertile patients and 80 fertile donors.
      Each ejaculate was subjected to a seminal analysis that included the classical
      parameters seminal volume, sperm concentration, sperm motility, and sperm
      morphology, as well as sperm DNA fragmentation (patients only). Polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP) and PCR multiplex
      methods were carried out for genotyping. RESULTS: Statistically significant
      differences were found between fertile donors and infertile patients for SNP CAT
      C-262T; the CC genotype was related with a twofold increased risk of infertility
      (odds ratio [OR] = 2.262; 95% confidence interval [CI] = 1.369-3.733; P = 0.001),
      whereas the CT genotype was associated with a protective effect (OR = 0.401; 95%
      CI = 0.241-0.667; P = 0.001). Surprisingly, the SOD2 Ile58ssThr SNP was not
      represented in the sample population, so its frequency in the current population
      frequenting fertility clinics in Madrid may be very low. CONCLUSIONS: Our results
      suggest that the CAT SNP C-262T is potentially associated with an increased risk
      of male infertility.

PMID- 30191957
TI  - First-ever convulsive seizures in children presenting to the emergency
      department: risk factors for seizure recurrence and diagnosis of epilepsy.
AB  - AIM: Aetiologies of first-ever convulsive seizures may be diverse, not all
      leading to recurrence or epilepsy diagnosis. We aimed to describe the
      epidemiology of first-ever convulsive seizures in children, investigating risk
      factors for recurrence and epilepsy diagnosis. METHOD: This was a retrospective
      study of children presenting with a first-ever convulsive seizure to a tertiary
      care paediatric emergency department (PED) in Italy, in a 12-month period (2011
      2012). RESULTS: One hundred and eight children (57 males, 51 females) presented
      to the PED for a first-ever convulsive seizure; 90.7% were 6 months to 6 years
      old (median age 1y 10mo, mean 2y 7mo, range 0mo-14y 4mo). Seizure duration was
      less than 5 minutes in 76.8%. Seizures were 'unprovoked' in 19.4% and 'provoked'
      in 80.6%. At 4-year follow-up, 37.9% of patients experienced recurrence and 13.6%
      received a diagnosis of epilepsy. Factors significantly associated with
      recurrence were the 'unprovoked' nature of the first seizure, multiple seizures
      in the first 24 hours, positive family history of febrile seizures or epilepsy,
      and pre-existing neurological conditions/problems. Factors significantly
      associated with a diagnosis of epilepsy were the 'unprovoked' nature of the first
      seizure, age older than 6 years, pre-existing neurological conditions/problems,
      and focal onset of first seizure. INTERPRETATION: Children presenting to the PED
      with first-ever convulsive seizures represent a heterogeneous group. The
      identification of prognostic factors for recurrence and epilepsy diagnosis may
      help provide tailored counselling and follow-up. WHAT THIS PAPER ADDS: Seizures
      were 'unprovoked' in 19.4% and 'provoked' in 80.6% of children presenting to the
      emergency department. At 4-year follow-up, 37.9% relapsed, and 13.6% received a
      diagnosis of epilepsy. 'Unprovoked' first seizure, family history of febrile
      seizures, and pre-existing neurological conditions were associated with
      recurrence. 'Unprovoked' first seizure, age younger than 6 years, and pre
      existing neurological conditions were associated with epilepsy diagnosis.

PMID- 30191956
TI  - Circulating insulin-like growth factor I in relation to melanoma risk in the
      European Prospective Investigation into Cancer and Nutrition.
AB  - Insulin-like growth factor (IGF-I) regulates cell proliferation and apoptosis,
      and is thought to play a role in tumour development. Previous prospective studies
      have shown that higher circulating concentrations of IGF-I are associated with a
      higher risk of cancers at specific sites, including breast and prostate. No
      prospective study has examined the association between circulating IGF-I
      concentrations and melanoma risk. A nested case-control study of 1221 melanoma
      cases and 1221 controls was performed in the European Prospective Investigation
      into Cancer and Nutrition cohort, a prospective cohort of 520,000 participants
      recruited from 10 European countries. Conditional logistic regression was used to
      estimate odds ratios (ORs) for incident melanoma in relation to circulating IGF-I
      concentrations, measured by immunoassay. Analyses were conditioned on the
      matching factors and further adjusted for age at blood collection, education,
      height, BMI, smoking status, alcohol intake, marital status, physical activity,
      and in women only, use of menopausal hormone therapy. There was no significant
      association between circulating IGF-I concentration and melanoma risk (OR for
      highest vs lowest fifth=0.93 (95% confidence interval (CI): 0.71 to 1.22)). There
      was no significant heterogeneity in the association between IGF-I concentrations
      and melanoma risk when subdivided by sex, age at blood collection, BMI, height,
      age at diagnosis, time between blood collection and diagnosis, or by anatomical
      site or histological subtype of the tumour (Pheterogeneity>=0.078). We found no
      evidence for an association between circulating concentrations of IGF-I measured
      in adulthood and the risk of melanoma. This article is protected by copyright.
      All rights reserved.

PMID- 30191959
TI  - MicroRNA-10b expression predicts long-term survival in patients with solid tumor.
AB  - BACKGROUND: Numerous studies have evaluated the significance of the microRNA-10b
      (miR-10b) in the development and progression of many cancers. Their findings
      revealed that increased expression of miR-10b is associated with unfavorable
      prognosis in patients with cancer. RESULTS: A total of 1,834 patients from 19
      studies were included in this study. A significantly shorter overall survival was
      observed in patients with increased expression of miR-10b (hazard ratio [HR] =
      1.99, 95% confidence interval [CI]: 1.51-2.61). Statistical significance was also
      observed in subgroup meta-analysis stratified by the cancer type, cutoff value,
      analysis type, and sample size. Also, patients with a high expression level of
      miR-10b had a poorer disease-free survival rate (HR = 1.18, 95% CI: 1.05-1.33).
      In addition, the pooled odds ratios (ORs) showed that increased miR-10b was also
      associated with positive lymph node metastasis (OR = 2.09, 95% CI: 1.45-3.03),
      distant metastasis (OR = 2.40, 95% CI: 1.57-3.67), tumor size (OR = 3.86, 95% CI:
      2.25-6.64), and poor clinical stage (OR = 5.02, 95% CI: 3.37-7.47). MATERIALS AND
      METHODS: A systematic literature search was conducted on a number of electronic
      databases, including PubMed, Embase, Web of Science, China National Knowledge
      Infrastructure, Springer, Google Scholar, and Gene expression omnibus. We
      retrieved the relevant articles to examine the association between the miR-10b
      expression levels and patients' prognosis. The meta-analysis was conducted using
      the RevMan 5.2 software and Stata SE12.0 software. CONCLUSIONS: High miR-10b
      expression was correlated with poor clinical outcome, which indicated the
      potential clinical use of miR-10b as a molecular biomarker for cancer,
      particularly in assessing prognosis for patients with cancers. Further studies
      should be performed to verify the clinical utility of miR-10b in human solid
      tumors.

PMID- 30191960
TI  - The IL-1/IL-1R axis induces greater fibroblast-derived chemokine release in human
      papillomavirus-negative compared to positive oropharyngeal cancer.
AB  - Human papillomavirus (HPV) is now recognised as a major aetiological agent in the
      pathogenesis of oropharyngeal carcinoma (OPC). HPV-positive tumours are
      associated with better outcomes compared to HPV-negative tumours, possibly due to
      differences in their aetiology and/or the tumour microenvironment. Increased
      numbers of tumour-associated leukocytes have been observed in many cancers
      including OPC, with variable influence on prognosis depending on the leukocyte
      subpopulation investigated. Whether HPV status influences leukocyte recruitment
      to OPC remains unknown. This in-vitro study examined differences in the
      chemoattractant capacity of HPV-positive and HPV-negative OPC cell lines. Gene
      and protein expression analysis demonstrated that whilst both monocultures of HPV
      positive and HPV-negative cell lines, along with normal tonsillar fibroblasts
      (NTF), expressed low chemokine levels, NTF cultured with conditioned medium from
      HPV-negative OPC cells expressed significantly higher levels of all chemokines
      tested compared to NTF incubated with the medium from HPV-positive OPC cell
      lines. HPV-negative OPC lines expressed IL-1beta mRNA whereas HPV-positive cells
      did not, and NTF constitutively expressed IL-1R1. Pre-treatment with the IL-R
      antagonist, anakinra or siRNA to IL-1R1 significantly reduced chemokine secretion
      from NTF stimulated with conditioned medium from HPV-negative tumour cells or
      recombinant IL-1beta (p < 0.05). These data suggest that secretion of chemokines
      is driven by the interaction between HPV-negative OPC cells and stromal
      fibroblasts through an IL-1/IL-1R-mediated mechanism that is less prominent
      within the HPV-positive tumour microenvironment. These observations may explain
      differences in leukocyte sub-populations recruited to HPV-positive versus
      negative OPC and indicate that HPV status is a key determinant in controlling the
      inflammatory tumour microenvironment.

PMID- 30191958
TI  - Aberrant expression of SETD1A promotes survival and migration of estrogen
      receptor alpha-positive breast cancer cells.
AB  - The histone H3 lysine 4-specific methyltransferase SETD1A is associated with
      transcription activation and is considered a key epigenetic regulator that
      modulates the cell cycle and metastasis in triple-negative breast cancer cells.
      However, the clinical role of SETD1A in estrogen receptor (ER)-positive breast
      cancer cells remains unclear. Here, we examined whether SETD1A is a potential
      target for ERalpha-positive breast cancer therapy. SETD1A expression was
      upregulated in breast tumor tissue compared to that in normal breast tissue.
      Moreover, ER-target genes regulated by SETD1A were particularly enriched in cell
      cycle and cancer pathways. SETD1A is involved in histone H3K4 methylation,
      subsequent recruitment of ERalpha, and the establishment of accessible chromatin
      structure at the enhancer region of ERalpha target genes. In addition to ERalpha
      target genes, other cell survival genes were also downregulated by SETD1A
      depletion in MCF-7 cells, leading to significant decrease in cell proliferation
      and migration, and spontaneous induction of apoptosis. We also found that miR
      1915-3p functioned as a novel regulator of SETD1A expression in breast cells.
      Importantly, the growth of tamoxifen-resistant MCF-7 cells was effectively
      repressed by SETD1A knockdown. These results indicate that SETD1A may serve as a
      molecular target and prognostic indicator in ERalpha-positive breast cancer.

PMID- 30191961
TI  - Oropharyngeal colostrum in preventing mortality and morbidity in preterm infants.
AB  - BACKGROUND: Placing a small volume of colostrum directly onto the buccal mucosa
      of preterm infants during the early neonatal period may provide immunological and
      growth factors that stimulate the immune system and enhance intestinal growth.
      These benefits could potentially reduce the risk of infection and necrotising
      enterocolitis (NEC) and improve survival and long-term outcome. OBJECTIVES: To
      determine if early (within the first 48 hours of life) oropharyngeal
      administration of mother's own fresh or frozen/thawed colostrum can reduce rates
      of NEC, late-onset invasive infection, and/or mortality in preterm infants
      compared with controls. To assess trials for evidence of safety and harm (e.g.
      aspiration pneumonia). To compare effects of early oropharyngeal colostrum (OPC)
      versus no OPC, placebo, late OPC, and nasogastric colostrum. SEARCH METHODS: We
      used the standard search strategy of the Cochrane Neonatal Review Group to search
      the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 8),
      MEDLINE via PubMed (1966 to August 2017), Embase (1980 to August 2017), and the
      Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to August
      2017). We also searched clinical trials registries for ongoing and recently
      completed trials (clinicaltrials.gov; the World Health Organization International
      Trials Registry (www.whoint/ictrp/search/en/), and the ISRCTN Registry),
      conference proceedings, and the reference lists of retrieved articles for
      randomised controlled trials and quasi-randomised trials. We performed the last
      search in August 2017. We contacted trial investigators regarding unpublished
      studies and data. SELECTION CRITERIA: We searched for published and unpublished
      randomised controlled trials comparing early administration of oropharyngeal
      colostrum (OPC) versus sham administration of water, oral formula, or donor
      breast milk, or versus no intervention. We also searched for studies comparing
      early OPC versus early nasogastric or nasojejunal administration of colostrum. We
      considered only trials that included preterm infants at < 37 weeks' gestation. We
      did not limit the review to any particular region or language. DATA COLLECTION
      AND ANALYSIS: Two review authors independently screened retrieved articles for
      inclusion and independently conducted data extraction, data analysis, and
      assessments of 'Risk of bias' and quality of evidence. We graded evidence quality
      using the Grading of Recommendations Assessment, Development and Evaluation
      (GRADE) approach. We contacted study authors for additional information or
      clarification when necessary. MAIN RESULTS: We included six studies that compared
      early oropharyngeal colostrum versus water, saline, placebo, or donor, or versus
      no intervention, enrolling 335 preterm infants with gestational ages ranging from
      25 to 32 weeks' gestation and birth weights of 410 to 2500 grams. Researchers
      found no significant differences between OPC and control for primary outcomes -
      incidence of NEC (typical risk ratio (RR) 1.42, 95% confidence interval (CI) 0.50
      to 4.02; six studies, 335 infants; P = 0.51; I2 = 0%; very low-quality evidence),
      incidence of late-onset infection (typical RR 0.86, 95% CI 0.56 to 1.33; six
      studies, 335 infants; P = 0.50; I2 = 0%; very low-quality evidence), and death
      before hospital discharge (typical RR 0.76, 95% CI 0.34 to 1.71; six studies, 335
      infants; P = 0.51; I2 = 0%; very low-quality evidence). Similarly, meta-analysis
      showed no difference in length of hospital stay between OPC and control groups
      (mean difference (MD) 0.81, 95% CI -5.87 to 7.5; four studies, 293 infants; P =
      0.65; I2 = 49%). Days to full enteral feeds were reduced in the OPC group with MD
      of -2.58 days (95% CI -4.01 to -1.14; six studies, 335 infants; P = 0.0004; I2 =
      28%; very low-quality evidence).The effect of OPC was uncertain because of small
      sample sizes and imprecision in study results (very low-quality evidence).No
      adverse effects were associated with OPC; however, data on adverse effects were
      insufficient, and no numerical data were available from the included
      studies.Overall the quality of included studies was low to very low across all
      outcomes. We downgraded GRADE outcomes because of concerns about allocation
      concealment and blinding, reporting bias, small sample sizes with few events, and
      wide confidence intervals. AUTHORS' CONCLUSIONS: Large, well-designed trials
      would be required to evaluate more precisely and reliably the effects of
      oropharyngeal colostrum on important outcomes for preterm infants.

PMID- 30191962
TI  - Mesenchymal stem cells as the game-changing tools in the treatment of various
      organs disorders: Mirage or reality?
AB  - Recently a growing attention in scientific community has been gathered on
      potential application of mesenchymal stem cells (MSCs) in various fields of
      medicine. Owing to the fact that they can be easily isolated from different
      sources, and simply proliferated in large quantities while keeping their original
      biological characteristics, they can be successfully used as cell-based
      therapeutics. Engineering MSCs and other type of stem cells to be carriers of
      therapeutic agents is a new tactic in the targeted gene and cell therapy of
      cancers and degenerative diseases. Various useful properties of MSCs including
      tropism toward tumor/injury site(s), weakly immunogenic, production of anti
      inflammatory molecules, and safety against normal tissues have made them prone
      for regenerative medicine, targeted therapy and treating injured tissues, and
      immunological abnormalities. In this review, we introduce latest advances,
      methods, and applications of MSCs in gene therapy of various malignant organ
      disorders. Additionally, we will cover the problems and challenges which
      researchers have faced with when trying to translate their basic experimental
      findings in MSCs research to clinically applicable therapeutics.

PMID- 30191963
TI  - Cell shape alteration during adipogenesis is associated with coordinated matrix
      cues.
AB  - Obesity has become one of the leading pathophysiologic disorders in recent years.
      Adipose tissue is the main tissue related to obesity and is known to play a role
      in various physiological complications, including type 2 diabetes. To better
      understand how the fat tissue develops, we used an in vitro live cell imaging
      system to quantify the adipogenesis by means of nondestructive digital imaging to
      monitor the accumulation of intracellular lipid droplets (LDs), a hallmark of
      adipogenesis, from the macro- to the micro-scale. Analyzing the cells' shape at
      the single-cell level allows to quantify the cells' shape change from a
      fibroblast to spherical morphology, indicating the start of adipogenesis. To
      reveal the molecular alterations, we applied a proteomic approach using high
      resolution mass spectrometry of the proliferation, confluent fibroblasts and of
      adipocytes. During this process, we noted the reorganization of the cells'
      extracellular matrix (ECM) network microenvironment from fibrillary collagen
      types I, III and V to collagens IV and VI, which affected the cells niche. The
      changes in ECM are translated for cytoskeleton remodeling according to cell fate
      determining mechanisms. We quantified the cytoskeleton rearrangement of long
      oriented actin fibers or short cortical and disorganized fibers, associated with
      LDs accumulation in adipocytes. Developing in vitro models and analytical methods
      enable us to study differentiation into adipocytes that will advance our
      understanding regarding the niche conditions that affect adipogenesis.
      Consequently, this will enable the development of new modalities to prevent
      obesity and its deleterious outcomes and to develop potential treatments to
      battle pathophysiology-related diseases.

PMID- 30191964
TI  - An assessment of progress in cancer control.
AB  - This article summarizes cancer mortality trends and disparities based on data
      from the National Center for Health Statistics. It is the first in a series of
      articles that will describe the American Cancer Society's vision for how cancer
      prevention, early detection, and treatment can be transformed to lower the cancer
      burden in the United States, and sets the stage for a national cancer control
      plan, or blueprint, for the American Cancer Society goals for reducing cancer
      mortality by the year 2035. Although steady progress in reducing cancer mortality
      has been made over the past few decades, it is clear that much more could, and
      should, be done to save lives through the comprehensive application of currently
      available evidence-based public health and clinical interventions to all segments
      of the population. CA Cancer J Clin 2018;000:000-000. (c) 2018 American Cancer
      Society.

PMID- 30191965
TI  - Genetic polymorphisms, forensic efficiency, and phylogenetic analysis of 15
      autosomal STR loci in the Uygur population of Ili Kazakh Autonomous Prefecture,
      Northwestern China.
AB  - The genetic polymorphisms of 15 autosomal short tandem repeat (STR) loci were
      analyzed in 449 individuals of the Uygur population from Ili Kazakh Autonomous
      Prefecture, Northwestern China. Phylogenetic analysis was performed among the Ili
      Uygur population and other relevant populations. The neighbor-joining tree and
      multidimensional scaling plot were generated based on the Nei's standard genetic
      distance. We found a total of 173 alleles with corresponding frequencies ranging
      from 0.5022 to 0.0011. The combined powers of discrimination and exclusion for
      the 15 autosomal STR loci were 0.99999999985 and 0.99999880065, respectively.
      Population comparisons indicated that the Ili Uygur population had a relatively
      close genetic relationship with the Uygur populations from other regions of
      China. The pairwise genetic distance and P-values between Ili Uygur and 10
      published populations showed that no statistically significant differences
      existed between the Ili Uygur population and the Kashi, Kashgar, and Kotan Uygur.
      Therefore, the Ili Uygur population has its own unique Uygur genetic
      characteristics that were different from the other ethnic populations of China.

PMID- 30191967
TI  - DUSP1 recuses diabetic nephropathy via repressing JNK-Mff-mitochondrial fission
      pathways.
AB  - Excessive mitochondrial fission has been identified as the pathogenesis of
      diabetic nephropathy (DN), although the upstream regulatory signal for
      mitochondrial fission activation in the setting of DN remains unknown. In the
      current study, we found that dual-specificity protein phosphatase-1 (DUSP1) was
      actually downregulated by chronic hyperglycemia stimulus. Lower DUSP1 expression
      was associated with glucose metabolism disorder, renal dysfunction, kidney
      hypertrophy, renal fibrosis, and glomerular apoptosis. At the molecular level,
      defective DUSP1 expression activated JNK pathway, and the latter selectively
      opened mitochondrial fission by modulating mitochondrial fission factor (Mff)
      phosphorylation. Excessive Mff-related mitochondrial fission evoked mitochondrial
      oxidative stress, promoted mPTP opening, exacerbated proapoptotic protein leakage
      into the cytoplasm, and finally initiated mitochondria-dependent cellular
      apoptosis in the setting of diabetes. However, overexpression of DUSP1
      interrupted Mff-related mitochondrial fission, reducing hyperglycemia-mediated
      mitochondrial damage and thus improving renal function. Overall, we have shown
      that DUSP1 functions as a novel malefactor in diabetic renal damage that mediates
      via modifying Mff-related mitochondrial fission. Thus, finding strategies to
      regulate the balance of the DUSP1-JNK-Mff signaling pathway and mitochondrial
      homeostasis may be a therapeutic target for treating diabetic nephropathy in
      clinical practice.

PMID- 30191966
TI  - Defective bone repair in diclofenac treated C57Bl6 mice with and without
      lipopolysaccharide induced systemic inflammation.
AB  - Bone repair after trauma or surgical intervention involves a tightly regulated
      cascade of events that starts with hemostasis and an inflammatory response, which
      are critical for successful healing. Nonsteroidal anti-inflammatory drugs (NSAID)
      are routinely prescribed for pain relief despite their potential inhibitory
      effect on bone repair. The goal of this study was to determine the impact of
      administration of the non-selective NSAID diclofenac in the inflammatory phase of
      bone repair in mice with or without lipopolysaccharide-induced systemic
      inflammation. Repair of femoral window defects was characterized using micro
      computed tomography imaging and histological analyses at 2 weeks postoperative.
      The data indicate (a) impaired bone regeneration associated with reduced
      osteoblast, osteoclast, and macrophage activity; (b) changes in the number,
      activity, and distribution of mast cells in regenerating bone; and (c) impaired
      angiogenesis due to a direct toxic effect of diclofenac on vascular endothelial
      cells. The results of this study provide strong evidence to support the
      conjecture that administration of NSAIDs in the first 2 weeks after orthopaedic
      surgery disrupts the healing cascade and exacerbates the negative effects of
      systemic inflammation on the repair process.

PMID- 30191968
TI  - KRT1 gene silencing ameliorates myocardial ischemia-reperfusion injury via the
      activation of the Notch signaling pathway in mouse models.
AB  - Myocardial ischemia and reperfusion injury (MIRI) includes major drawbacks, such
      as excessive formation of free radicals and also overload of calcium, which lead
      to cell death, tissue scarring, and remodeling. The current study aims to explore
      whether KRT1 silencing may ameliorate MIRI via the Notch signaling pathway in
      mouse models. Myocardial tissues were used for the determination of the positive
      rate of KRT1 protein expression, apoptosis of myocardial cells, creatine kinase
      (CK) and lactate dehydrogenase (LDH) expression, expression of related biomarkers
      as well as myocardial infarction area. The transfected myocardial cells were
      treated with KRT1-siRNA, Jagged1, and DAPT (inhibitor of Notch-1 signaling
      pathway). The expression of KRT1, NICD, Hes1, Bcl-2, and Bax protein was
      detected. The MTT assay was applied for cell proliferation and flow cytometry was
      used for cell apoptosis. Mice with MIRI had a higher positive rate of KRT1
      protein expression, apoptosis of myocardial cells, CK and LDH expression,
      myocardial infarction area, increased expression of MDA, NO, SDH, IL-1, IL-6, TNF
      alpha, CRP, KRT1, Bax protein, CK, and LDH, and decreased expression of SOD,
      NICD, Hes1, and Bcl-2. The downregulation of KRT1 led to decreased expression of
      KRT1 and Bax protein, increased expression of NICD, Hes1, and Bcl-2, decreased
      cell apoptosis, and improved cell proliferation. The inhibition of the Notch
      signaling pathway leads to reduced expression of Bax, increased expression of
      NICD, Hes1, and Bcl 2, and also decreased cell apoptosis and increased cell
      proliferation. Our data conclude that KRT1 silencing is able to make MIRI better
      by activating the Notch signaling pathway in mice.

PMID- 30191970
TI  - Methylation of CLEC14A is associated with its expression and lung adenocarcinoma
      progression.
AB  - Our main objective is probing the effect of methylation of CLEC14A on its
      expression and lung adenocarcinoma (LUAD) progression. Microarray analysis was
      utilized to screen out differentially downregulated genes with hypermethylation
      in LUAD tissues. The CLEC14A expression level was measured by western blot
      analysis and qRT-PCR. Methylation-specific-PCR was performed to evaluate
      methylation status of CLEC14A. The 3-(4,5-Dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromid (MTT) assay was used to check the relation between
      CLEC14A expression and cell proliferation. Cell cycle, cell apoptosis, migration,
      and invasion were respectively detected by the flow cytometry assay, wound
      healing assay, and transwell assay. Tumor xenograft models were established for
      investigating the effect of CLEC14A on tumor formation. CLEC14A expression in
      LUAD tissues was impaired compared with that in adjacent tissues, and CLEC14A
      promoter was highly methylated in LUAD. Overexpressing CLEC14A or inhibiting the
      methylation level of CLEC14A in A549 and LTEP-a-2 cells impeded the duplication
      of LUAD cells, promoted apoptosis, attenuated cell migration, and invasion
      ability, and arrested cell cycle at the G0/G1 phase. Overexpression of CLEC14A
      inhibited tumorigenesis of LUAD cells in nude mice. The promoter of CLEC14A is
      methylated in LUAD, leading to downregulation of CLEC14A in LUAD. CLEC14A acts as
      an antitumor role in LUAD by suppressing cell proliferation, migration, invasion,
      promoting cell apoptosis, and reducing tumorigenicity in nude mice. Thus, the
      inhibition of CLEC14A methylation is a novel strategy for the clinic treatment of
      LUAD.

PMID- 30191969
TI  - PP-22 promotes autophagy and apoptosis in the nasopharyngeal carcinoma cell line
      CNE-2 by inducing endoplasmic reticulum stress, downregulating STAT3 signaling,
      and modulating the MAPK pathway.
AB  - Paris polyphylla var. yunnanensis, named Chong Lou, is considered an antitumor
      substance. In this study, we investigated the effect of PP-22, a monomer purified
      from P. polyphylla var. yunnanensis, on the nasopharyngeal carcinoma cell line
      CNE-2 in vitro. The results showed that PP-22 could inhibit the proliferation of
      CNE-2 cells via the induction of apoptosis, with evidence of the characteristic
      morphological changes in the apoptosis in the nucleus and an increase in Annexin
      V-positive cells. In addition, we found that PP-22 could activate the p38 mitogen
      activated protein kinase (MAPK) pathway and that this activation was reversed by
      SB203580, a specific inhibitor of the p38 MAPK pathway. In contrast, PP-22
      promoted apoptosis via an intrinsic pathway, including the endoplasmic reticulum
      stress pathway, in a caspase-dependent manner. A further study showed that PP-22
      also induced apoptosis by downregulating the signal transducers and activators of
      transcription 3 (STAT3) pathway, and the inhibitory effect was also confirmed by
      STAT3 small interfering RNA. In addition, PP-22 could promote autophagy by
      inhibiting the extracellular regulated protein kinases (ERK) pathway. And
      autophagy plays a protective role against apoptosis. Together, these data show
      that PP-22 promotes autophagy and apoptosis in the nasopharyngeal carcinoma CNE-2
      cell line.

PMID- 30191971
TI  - The prognostic and therapeutic values of long noncoding RNA PANDAR in colorectal
      cancer.
AB  - Long noncoding RNAs (lncRNAs) consist of 200 nucleotide sequences that play
      essential roles in different processes, including cell proliferation, and
      differentiation. There is evidence showing that the dysregulation of lncRNAs
      promoter of CDKN1A antisense DNA damage-activated RNA (PANDAR) leads to the
      development and progression in several cancers including colorectal cancer, via
      p53-dependent manner. This suggests that these lncRNAs may be of value as
      prognostic indices and a therapeutic target, as a high expression of lncRNAs
      PANDAR is associated with poor prognosis. Furthermore, modulating lncRNAs PANDAR
      has been reported to induce apoptosis and inhibit the tumor growth through
      modulation of cell cycle and epithelial-mesenchymal transition (EMT) pathway. The
      aim of the current review was to provide an overview of the prognostic and
      therapeutic values of lncRNAs PANDAR in colorectal cancer.

PMID- 30191972
TI  - Phase 3 randomised study of avatrombopag, a novel thrombopoietin receptor agonist
      for the treatment of chronic immune thrombocytopenia.
AB  - Avatrombopag, an oral thrombopoietin receptor agonist, was compared with placebo
      in a 6-month, multicentre, randomised, double-blind, parallel-group Phase 3
      study, with an open-label extension phase, to assess the efficacy and safety of
      avatrombopag (20 mg/day) in adults with chronic immune thrombocytopenia (ITP) and
      a platelet count <30 * 109 /l (ClinicalTrials.gov identifier NCT01438840). The
      primary endpoint was the cumulative number of weeks of platelet response
      (platelet count >=50 * 109 /l) without rescue therapy for bleeding; secondary
      endpoints included platelet response rate at day 8 and reductions in the use of
      concomitant medications. Amongst the 49 patients randomised, avatrombopag (N =
      32) was superior to placebo (N = 17) in the median cumulative number of weeks of
      platelet response (12.4 vs. 0.0 weeks, respectively; P < 0.0001). At day 8, a
      greater platelet response rate was also observed for patients treated with
      avatrombopag compared with placebo (65.63% vs. 0.0%; P < 0.0001), and use of
      concomitant ITP medications was also reduced amongst patients receiving
      avatrombopag. The safety profile of avatrombopag was consistent with Phase 2
      studies; the most common adverse events were headache and contusion. Overall,
      avatrombopag was well tolerated and efficacious for the treatment of chronic ITP.

PMID- 30191973
TI  - The role of microRNAs in 5-FU resistance of colorectal cancer: Possible
      mechanisms.
AB  - Colorectal cancer (CRC) is one of the most common cancers globally. Despite
      recent advances in therapeutic approaches, this cancer continues to have a poor
      prognosis, particularly when diagnosed late. 5-Fluorouracil (5-FU) has been
      commonly prescribed for patients with CRC, but resistance to 5-FU is one of the
      main reasons for failure in the treatment of this condition. Recently, microRNAs
      (miRNAs) have been established as a means of modifying the signaling pathways
      involved in initiation and progression of CRC and their role as oncogene or tumor
      suppressor have been investigated in various studies. Moreover, miRNAs through
      various mechanisms play an important role in inducing tumor resistance or
      sensitivity to anticancer drugs. Detecting and targeting these mechanisms may be
      a new therapeutic approach. This review summarizes the current knowledge about
      the potential roles of miRNAs in 5-FU resistance, with particular emphasis on
      molecular mechanism involved.

PMID- 30191974
TI  - Streptozotocin-induced type II diabetic rat administered with nonobesogenic high
      fat diet is highly susceptible to myocardial ischemia-reperfusion injury: An
      insight into the function of mitochondria.
AB  - RATIONALE: Our recent study suggested that ischemia-reperfusion (I/R) induced
      oxidative stress was minimal in the rat heart during initial stage of diabetes
      and the one that progressed to diabetic cardiomyopathy (DCM), despite having
      higher infarct and low cardiac performance. Mitochondrial dysfunction is an
      important mediator for adverse outcome in rat heart affected with diabetes, which
      is also a potential contributor for the cardiac reperfusion injury. OBJECTIVE:
      The current study aims to evaluate the susceptibility of diabetes heart with or
      without myopathy to I/R injury and its influence on cardiac mitochondrial
      function. METHODS AND RESULTS: Male Wistar rats (3 weeks old) were fed with high
      fat diet for 8 weeks followed by diabetes mellitus (DM) induction via
      streptozotocin (35 mg/kg body weight) and maintained for further 4 weeks. The
      animal displayed cardiomyopathy characteristics like hypertrophy, fibrosis, and
      insulin resistance-termed diabetic cardiomyopathy (DCM). To study the specific
      effect of DCM on I/R, we included diabetic rats without cardiomyopathy. Induction
      of I/R in different groups suggested higher vulnerability to injury in DCM rat
      hearts than DM and normal (measured via hemodynamics, triphenyltetrazolium
      chloride stain, and apoptotic markers). Mitochondrial function at the
      subpopulation level was evaluated with respect to adenosine triphosphate (ATP)
      concentration, membrane potential, swelling behavior, and oxidative stress,
      wherein the results confirmed I/R-induced mitochondrial dysfunction. Unlike
      normal heart, DM, and DCM heart challenged to I/R exhibited altered ATP producing
      capacity among subsarcolemmal and interfibrillar mitochondria. CONCLUSION: The
      above results suggest that mitochondrial changes associated with diabetes and
      cardiomyopathy significantly contribute to the adverse outcome of I/R injury.

PMID- 30191975
TI  - Exosomes and microRNAs: New potential therapeutic candidates in Alzheimer disease
      therapy.
AB  - Exosomes are biological nanocarriers which could be involved in a variety of
      basic physiological events. They exert their effects via targeting their cargos
      (i.e., DNAs, messenger RNAs, microRNAs [miRNAs], and proteins) to host cells,
      which led to change behaviors of recipient cells. One of the important aspects of
      exosomes is the roles of them in disease conditions. Increasing evidence
      indicated that exosomes are one of the main players in Alzheimer's disease (AD)
      pathogenesis. Hence, it seems that these nanocarriers could be used as diagnostic
      and therapeutic biomarkers in AD treatment. Another important player in AD
      pathogenesis is miRNA. MiRNAs are short noncoding RNAs which exert their effects
      as epigenetic regulators. These molecules involved in different stages of AD.
      Therefore, miRNAs could be used as prognostic, diagnostic, and therapeutic
      biomarkers in AD. Here, we summarized various roles of exosomes and application
      of them in AD pathogenesis. Moreover, we highlighted the utilization of miRNAs as
      a therapeutic option in AD therapy.

PMID- 30191976
TI  - Nicotinamide phosphoribosyl transferase regulates cell growth via the Sirt1/P53
      signaling pathway and is a prognosis marker in colorectal cancer.
AB  - Colorectal cancer (CRC) is the third most common malignancy, and the metabolic
      properties of CRC cells include enhanced aerobic glycolysis (the Warburg effect).
      Nicotinamide phosphoribosyl transferase (NAMPT) is one of the crucial enzymes
      that regulate the activity of nicotinamide adenine dinucleodinucleotide dependent
      enzymes. Targeting NAMPT is a potential method of CRC therapy. Nevertheless, the
      underlying clinical implications and regulatory mechanisms of NAMPT in CRC remain
      unclear. In this study, we showed that NAMPT protein expression was increased in
      subjects with rectal localization compared with those with colon localization,
      and NAMPT was a poor prognostic marker for the overall survival rate in patients
      with CRC. In addition, the NAMPT inhibitor FK866 or lentivirus-mediated silencing
      induced CRC cell growth inhibition. Mechanistically, NAMPT regulated Sirt1 and
      P53 expression and induced G0/G1 cell cycle arrest, along with the upregulation
      of downstream p21 and downregulation of cyclin D1, cyclin E1, and cyclin E2
      expression. FK866 administration or knockdown of NAMPT induced CRC cell apoptosis
      via upregulation of caspase-3. In conclusion, NAMPT regulated Sirt1/P53 signaling
      during CRC cell growth and warrants further investigation for clinical
      administration in CRC.

PMID- 30191977
TI  - Nanostructured lipid carriers containing rapamycin for prevention of corneal
      fibroblasts proliferation and haze propagation after burn injuries: In vitro and
      in vivo.
AB  - Chemical burns are a major cause of corneal haze and blindness. Corticosteroids
      are commonly used after corneal burns to attenuate the severity of the
      inflammation-related fibrosis. While research efforts have been aimed toward
      application of novel therapeutics. In the current study, a novel drug delivery
      system based nanostructured lipid carriers (NLCs) were designed to treat corneal
      alkaline burn injury. Rapamycin, a potent inhibitor of mammalian target of
      rapamycin pathway, was loaded in NLCs (rapa-NLCs), and the NLCs were
      characterized. Cell viability assay, cellular uptake of NLCs, and in vitro
      evaluation of the fibrotic/angiogenic genes suppression by rapa-NLCs were carried
      out on human isolated corneal fibroblasts. Immunohistochemistry (IHC) assays were
      also performed after treatment of murine model of corneal alkaline burn with rapa
      NLCs. According to the results, rapamycin was efficiently loaded in NLCs. NLCs
      could enhance coumarin-6 fibroblast uptake by 1.5 times. Rapa-NLCs efficiently
      downregulated platelet-derived growth factor and transforming growth factor beta
      genes in vitro. Furthermore, proliferation of fibroblasts, a major cause of
      corneal haze after injury, reduced. IHC staining of treated cornea with alpha
      smooth muscle actin and CD34 + antibodies showed efficient prevention of
      myofibroblasts differentiation and angiogenesis, respectively. In conclusion,
      ocular delivery of rapamycin using NLCs after corneal injury may be considered as
      a promising antifibrotic/angiogenic treatment approach to preserve patient
      eyesight.

PMID- 30191978
TI  - Chemoresistance of cancer floating cells is independent of their ability to form
      3D structures: Implications for anticancer drug screening.
AB  - Three-dimensional (3D) culture systems such as floating spheroids (FSs) and
      floating tumorspheres (FTs) are widely used as tumor models of chemoresistance.
      FTs are considered to be enriched in cancer stem-like cells (CS-LCs). In this
      study, we used cancer cell lines (lung H460, prostate LnCAP, and breast MCF-7)
      able to form FSs under anchorage-independent conditions and compared with cell
      lines (prostate PC3 and breast MDA-MB-231) that cannot form FSs under similar
      conditions. Independent of their ability to form FTs all cell lines growing under
      anchorage-independent conditions become highly resistant to obatoclax,
      colchicine, and hydroxyurea. We used anti-E-cadherin antibody (that blocked the
      formation of FSs) and demonstrated that floating LnCAP cells showed similar
      chemoresistance regardless of the formation of spheroids. Our results demonstrate
      that the development of chemoresistance is not because of the formation of a
      complex 3D structure and/or enrichment of CS-LCs but is likely the result of cell
      detachment per se and their ability to survive under anchorage-independent
      conditions. We propose that FSs and FTs could be useful models to study
      chemoresistance of cancer cells associated with cell detachment (e.g.,
      circulating tumor cells) but they may not be representative of other types of
      chemoresistance that arise in vivo in attached cells.

PMID- 30191979
TI  - Endotoxin regulates matrix genes increasing reactive oxygen species generation by
      intercellular communication between palmitate-treated hepatocyte and stellate
      cell.
AB  - Previous studies have shown that gut-derived bacterial endotoxins contribute in
      the progression of simple steatosis to steatohepatitis, although the mechanism(s)
      remains inaccurate to date. As hepatic stellate cells (HSC) play a pivotal role
      in the accumulation of excessive extracellular matrix (ECM), leading to collagen
      deposition, fibrosis, and perpetuation of inflammatory response, an in vitro
      model was developed to investigate the crosstalk between HSC and hepatocytes
      (human hepatoma cell) pretreated with palmitate. Bacterial lipopolysaccharide
      (LPS) stimulated HSC with phosphorylation of the p38 mitogen-activated protein
      kinase/NF-kappaB pathway, while several important pro-inflammatory cytokines were
      upregulated in the presence of hepatocyte-HSC. Concurrently, fibrosis-related
      genes were regulated by palmitate and the inflammatory effect of endotoxin where
      cells were more exposed or sensitive to reactive oxygen species (ROS). This
      interaction was accompanied by increased expression of the mitochondrial master
      regulator, proliferator-activated receptor gamma coactivator alpha, and a
      cytoprotective effect of the agent N-acetylcysteine suppressing ROS production,
      transforming growth factor-beta1, and tissue inhibitor of metalloproteinase-1. In
      summary, our results demonstrate that pro-inflammatory mediators LPS-induced
      promote ECM rearrangement in hepatic cells transcriptionally committed to the
      regulation of genes encoding enzymes for fatty acid metabolism in light of
      differences that might require an alternative therapeutic approach targeting ROS
      regulation.

PMID- 30191980
TI  - Sevoflurane anesthesia represses neurogenesis of hippocampus neural stem cells
      via regulating microRNA-183-mediated NR4A2 in newborn rats.
AB  - Sevoflurane has been commonly utilized in nonobstetric surgeries in pregnant
      women, and its impacts on fetal brain are still not completely known. Ectopic
      NR4A2 expression has been reported to be related with familial Parkinson disease,
      and through dual luciferase we found that NR4A2 is a target gene of microRNA-183
      (miR-183). We proposed a hypothesis that miR-183 may participate in the process
      by targeting NR4A2 in neurons after sevoflurane anesthesia. To verify the effect
      of sevoflurane on hippocampal neural stem cells (NSCs) proliferation and
      differentiation, we conducted EdU assay and immunofluorescence staining. Next,
      for better understanding of the impact of miR-183, we altered the miR-183
      expression using mimic and inhibitor. Meanwhile, the targeting relationship
      between miR-183 and NR4A2 was validated by a bioinformatics website and dual
      luciferase reporter gene assay. Finally, expressions of miR-184, NR4A2, SRY (sex
      determining region Y)-box 2 (Sox2), and brain-derived neurotrophic factor (BDNF)
      were determined and evaluated by reverse transcription quantitative polymerase
      chain reaction and western blot analysis. First, sevoflurane was determined a
      crucial factor in biological behaviors of hippocampal NSCs. Moreover, upregulated
      miR-183 expression by mimic inhibited the proliferation and differentiation of
      NSCs. Sevoflurane negatively regulated NR4A2 and Sox2 expressions but positively
      regulated miR-183 and BDNF expressions. Our findings revealed the underlying
      novel mechanism by which sevoflurane inhibits hippocampal NSC proliferation and
      differentiation through interaction with miR-183 and NR4A2. The study provides
      reliable reference for safe application of sevoflurane anesthesia in neonates.

PMID- 30191981
TI  - Heme oxygenase 1 regulates apoptosis induced by heat stress in bovine ovarian
      granulosa cells via the ERK1/2 pathway.
AB  - Heat stress can inhibit follicular development in dairy cows, and thus can affect
      their reproductive performance. Follicular granulosa cells can synthesize
      estrogen, that affects the development and differentiation of follicles by
      apoptosis. Heme oxygenase 1 (HO-1/heat shock protein 32) plays an antiapoptotic
      and cytoprotective role in various cells during stress-induced apoptosis, but
      little is known about its definitive function in bovine (ovarian) granulosa cells
      (bGCs). In our study, the roles and mechanism of HO-1 on the heat stress-induced
      apoptosis of bGCs were studied. Our results show that the expression of HO-1 was
      significantly increased under heat stress. Moreover, HO-1 silencing increased
      apoptosis, whereas its overexpression dampened apoptosis by regulating the
      expression of Bax/Bcl-2 and the levels of cleaved caspase-3. In addition, HO-1
      can also play a cytoprotective role by affecting estrogen levels and decomposing
      heme to produce biologically active metabolite carbon monoxide (CO). Meanwhile,
      CO significantly increased the level of HO-1, decreased Bax/Bcl-2 levels, and
      inhibited the activation of extracellular signal-regulated kinase 1/2 (ERK1/2)
      signaling pathway. The apoptosis of ovarian GCs can affect the secretion of
      estrogen and lead to disorder of the ovarian microenvironment, thus affecting the
      normal function of the ovary. Our results indicate that HO-1 acts as a
      cytoprotective enzyme and plays a protective role in heat-induced apoptosis of
      bGCs. In conclusion, HO-1 and its metabolite CO inhibit the apoptosis of bGCs
      induced by heat stress through the ERK1/2 pathway. The results of this study
      provide a valuable clue for improving the fertility of heat stressed cows in
      summer.

PMID- 30191982
TI  - Clinicopathological and prognostic value of lncRNA PANDAR expression in solid
      tumors: Evidence from a systematic review and meta-analysis.
AB  - PANDAR (promoter of CDKN1A antisense DNA damage activated RNA) has been shown to
      be aberrantly expressed in many types of cancer. Considering conflicting data,
      the current study was aimed to assess its potential role as a prognostic marker
      in malignant tumors. A comprehensive literature search of PubMed, Medline, and
      Web of Science was performed to identify all eligible studies describing the use
      of PANDAR as a prognostic factor for different types of cancer. Data related to
      overall survival (OS) and clinicopathologic features were collected and analyzed.
      The pooled hazard ratio (HR) and odds radio (OR) with a 95% confidence interval
      (CI) were used to estimate associations. Ten original studies containing 1,231
      patients were included. The results showed that in patients with cancer, high
      PANDAR expression is correlated with lymph node metastasis (LNM; OR = 2.57; 95%
      CI, 1.76-3.81; p < 0.001), tumor stage (OR = 2.90; 95% CI, 1.25-6.75; p = 0.013),
      and tumor size (OR = 1.79; 95% CI, 1.11-2.91; p = 0.018). However, sensitivity
      analysis further demonstrated a significant association between high PANDAR
      expression and OS, both in multivariate and univariate analysis models (pooled HR
      2.01; 95% CI, 1.17-3.44 and pooled HR 2.62; 95% CI, 1.98-3.47, respectively),
      after omitting one study. These results suggested that PANDAR expression might be
      indicative of advanced disease and poor prognosis in patients with cancer.
      Further studies are necessary to determine the value of this risk stratification
      biomarker in clinical management of patients with cancer.

PMID- 30191983
TI  - Hepatocyte growth factor promotes the proliferation of human embryonic stem cell
      derived retinal pigment epithelial cells.
AB  - Research that pertains to the molecular mechanisms involved in retinal pigment
      epithelial (RPE) development can significantly contribute to cell therapy
      studies. The effects of periocular mesenchymal cells on the expansion of RPE
      cells remain elusive. We have examined the possible proliferative role of
      hepatocyte growth factor (HGF) as a mesenchymal cell secretory factor against
      human embryonic stem cell derived RPE (hESC-RPE). We found that the conditioned
      medium of human mesenchymal stem cells from apical papilla and/or exogenous HGF
      promoted proliferation of the hESC-RPE cells as single cells and cell sheets, in
      addition to rabbit RPE sheets in vitro. Blockage of HGF signaling by HGF receptor
      inhibitor, PHA-665752, inhibited proliferation of hESC-RPE cells. However,
      differentiation of hESCs and human-induced pluripotent stem cells to a rostral
      fate and eye-field specification was unaffected by HGF. Our in vivo analysis
      showed HGF expression in periocular mesenchymal cells after optic cup formation
      in chicken embryos. Administration of HGF receptor inhibitor at this
      developmental stage in chicken embryos led to reduced eye size and
      disorganization of the RPE sheet. These findings suggested that HGF
      administration could be beneficial for obtaining higher numbers of hESC-RPE cells
      in human preclinical and clinical trials.

PMID- 30191984
TI  - Fusobacterium nucleatum and colorectal cancer: A mechanistic overview.
AB  - Colorectal cancer (CRC) is the third most prevalent cancer in the world. There
      are many risk factors involved in CRC. According to recent findings, the tumor
      microenvironment and feces samples of patients with CRC are enriched by
      Fusobacterium nucleatum. Thus, F. nucleatum is proposed as one of the risk
      factors in the initiation and progression of CRC. The most important mechanisms
      of Fusobacterium nucleatum involved in CRC carcinogenesis are immune modulation
      (such as increasing myeloid-derived suppressor cells and inhibitory receptors of
      natural killer cells), virulence factors (such as FadA and Fap2), microRNAs (such
      as miR-21), and bacteria metabolism. The aim of this review was to evaluate the
      mechanisms underlying the action of F. nucleatum in CRC.

PMID- 30191985
TI  - The potential therapeutic use of renin-angiotensin system inhibitors in the
      treatment of inflammatory diseases.
AB  - Inflammation is a normal part of the immune response to injury or infection but
      its dysregulation promotes the development of inflammatory diseases, which cause
      considerable human suffering. Nonsteroidal anti-inflammatory agents are the most
      commonly prescribed agents for the treatment of inflammatory diseases, but they
      are accompanied by a broad range of side effects, including gastrointestinal and
      cardiovascular events. The renin-angiotensin system (RAS) is traditionally known
      for its role in blood pressure regulation. However, there is increasing evidence
      that RAS signaling is also involved in the inflammatory response associated with
      several disease states. Angiotensin II increases blood pressure by binding to
      angiotensin type 1 (AT1 ) receptor, and direct renin inhibitors, angiotensin
      converting enzyme (ACE) inhibitors and AT1 receptor blockers (ARBs) are
      clinically used as antihypertensive agents. Recent data suggest that these drugs
      also have anti-inflammatory effects. Therefore, this review summarizes these
      recent findings for the efficacy of two of the most widely used antihypertensive
      drug classes, ACE inhibitors and ARBs, to reduce or treat inflammatory diseases
      such as atherosclerosis, arthritis, steatohepatitis, colitis, pancreatitis, and
      nephritis.

PMID- 30191986
TI  - Arsenic induces fibrogenic changes in human kidney epithelial cells potentially
      through epigenetic alterations in DNA methylation.
AB  - Arsenic contamination is a significant public health issue, and kidney is one of
      the target organ for arsenic-induced adverse effects. Renal fibrosis is a well
      known pathological stage frequently observed in progressive chronic kidney
      disease (CKD). Epidemiological studies implicate arsenic exposure to CKD, but the
      role of arsenic in kidney fibrosis and the underlying mechanism is still unclear.
      It is in this context that the current study evaluated the effects of long-term
      arsenic exposure on the cellular response in morphology, and marker genes
      expression with respect to fibrosis using human kidney 2 (HK-2) epithelial cells.
      Results of this study revealed that in addition to increased growth, HK-2 cells
      underwent phenotypic, biochemical and molecular changes indicative of epithelial
      mesenchymal transition (EMT) in response to the exposure to arsenic. Most
      importantly, the arsenic-exposed cells acquired the pathogenic features of
      fibrosis as supported by increased expression of markers for fibrosis, such as
      Collagen I, Fibronectin, transforming growth factor beta, and alpha-smooth muscle
      actin. Upregulation of fibrosis associated signaling molecules such as tissue
      inhibitor of metalloproteinases-3 and matrix metalloproteinase-2 as well as
      activation of AKT was also observed. Additionally, the expression of epigenetic
      genes (DNA methyltransferases 3a and 3b; methyl-CpG binding domain 4) was
      increased in arsenic-exposed cells. Treatment with DNA methylation inhibitor 5
      Aza-2'-dC reversed the EMT properties and restored the level of phospho-AKT.
      Together, these data for the first time suggest that long-term exposure to
      arsenic can increase the risk of kidney fibrosis. Additionally, our data suggest
      that the arsenic-induced fibrotic changes are, at least in part, mediated by DNA
      methylation and therefore potentially can be reversed by epigenetic therapeutics.

PMID- 30191987
TI  - Role of CXCL12-CXCR4 axis in ovarian cancer metastasis and CXCL12-CXCR4 blockade
      with AMD3100 suppresses tumor cell migration and invasion in vitro.
AB  - Ovarian cancer (OC) is a lethal gynecologic tumor, which brings its mortality to
      the head. CXCL12 and its receptor chemokine receptor 4 ( CXCR4) have been found
      to be highly expressed in OC and contribute to the disease progression by
      affecting tumor cell proliferation and invasion. Here, in this study, we aim to
      explore whether the blockade of CXCL12-CXCR4 axis with AMD3100 (a selective CXCR4
      antagonist) has effects on the progression of OC. On the basis of the gene
      expression omnibus database of OC gene expression chips, the OC differentially
      expressed genes were screened by microarray analysis. OC (nonmetastatic and
      metastatic) and normal ovarian tissues were collected to determine the
      expressions of CXCL12 and CXCR4. A series of AMD3100, shRNA against CXCR4, and
      pCNS-CXCR4 were introduced to treat CAOV3 cells with the highest CXCR4 was
      assessed. Cell viability, apoptosis, migration, and invasion were all evaluated.
      The microarray analysis screened out the differential expression of CXCL12-CXCR4
      in OC. CXCL12 and CXCR4 expressions were increased in OC tissues, particularly in
      the metastatic OC tissues. Downregulation of CXCR4 by AMD3100 or shRNA was
      observed to have a critical role in inhibiting cell proliferation, migration, and
      invasion of the CAOV3 OC cell line while promoting cell apoptosis. Overexpressed
      CXCR4 brought significantly promoting effects on the proliferation and
      invasiveness of OC cells. These results reinforce that the blockade of CXCL12
      CXCR4 axis with AMD3100 inhibits the growth of OC cells. The antitumor role of
      the inhibition of CXCL12-CXCR4 axis offers a preclinical validation of CXCL12
      CXCR4 axis as a therapeutic target in OC.

PMID- 30191988
TI  - The potential prognostic and therapeutic application of tissue and circulating
      microRNAs in cervical cancer.
AB  - Cervical cancer (CC) is a common malignancy in women and a major cause of cancer
      related mortality globally. Some novel biomarkers may enable the early diagnosis
      and monitoring of CC. MicroRNAs (miRNAs) are small noncoding RNAs that control
      gene translation at a posttranscriptional level. Hence the deregulation of these
      molecules can cause many diseases. There appears to be an association between
      aberrant miRNA expression and CC, but the molecular mechanisms involved in the
      development of CC remain unknown. The upregulation of some circulating miRNAs,
      for example, miRNA-20a, miRNA-203, miRNA-21, miRNA-205, miRNA-218, and miR-485-5,
      as well as tissue-specific miRNAs, for example, miR-7, miR-10a, miR-17-5p, miR
      135b, miR-149, and miR-203 have been found in patients with CC. There is also
      growing evidence for the importance of miRNAs in the development of drug
      resistance. This review therefore highlights recently published preclinical and
      clinical investigation performed on tissue specific and circulating miRNAs, as
      potential biomarkers for the detection of patients at early stages of CC, in the
      prediction of prognosis, and monitoring of their response to therapy.

PMID- 30191989
TI  - Muscarinic M5 receptors trigger acetylcholine-induced Ca2+ signals and nitric
      oxide release in human brain microvascular endothelial cells.
AB  - Basal forebrain neurons control cerebral blood flow (CBF) by releasing
      acetylcholine (Ach), which binds to endothelial muscarinic receptors to induce
      nitric (NO) release and vasodilation in intraparenchymal arterioles.
      Nevertheless, the mechanism whereby Ach stimulates human brain microvascular
      endothelial cells to produce NO is still unknown. Herein, we sought to assess
      whether Ach stimulates NO production in a Ca2+ -dependent manner in hCMEC/D3
      cells, a widespread model of human brain microvascular endothelial cells. Ach
      induced a dose-dependent increase in intracellular Ca2+ concentration ([Ca2+ ]i )
      that was prevented by the genetic blockade of M5 muscarinic receptors (M5
      mAchRs), which was the only mAchR isoform coupled to phospholipase Cbeta
      (PLCbeta) present in hCMEC/D3 cells. A comprehensive real-time polymerase chain
      reaction analysis revealed the expression of the transcripts encoding for type 3
      inositol-1,4,5-trisphosphate receptors (InsP3 R3), two-pore channels 1 and 2
      (TPC1-2), Stim2, Orai1-3. Pharmacological manipulation showed that the Ca2+
      response to Ach was mediated by InsP3 R3, TPC1-2, and store-operated Ca2+ entry
      (SOCE). Ach-induced NO release, in turn, was inhibited in cells deficient of M5
      mAchRs. Likewise, Ach failed to increase NO levels in the presence of l-NAME, a
      selective NOS inhibitor, or BAPTA, a membrane-permeant intracellular Ca2+ buffer.
      Moreover, the pharmacological blockade of the Ca2+ response to Ach also inhibited
      the accompanying NO production. These data demonstrate for the first time that
      synaptically released Ach may trigger NO release in human brain microvascular
      endothelial cells by stimulating a Ca2+ signal via M5-mAchRs.

PMID- 30191990
TI  - Immune responsive resolvin D1 programs peritoneal macrophages and cardiac
      fibroblast phenotypes in diversified metabolic microenvironment.
AB  - Bioactive lipid mediators derived from n-3 and n-6 fatty acids are known to
      modulate leukocytes. Metabolic transformation of essential fatty acids to
      endogenous bioactive molecules plays a major role in human health. Here we tested
      the potential of substrates; linoleic acid (LA) and docosahexaenoic acid (DHA)
      and their bioactive products; resolvin D1 (RvD1) and 12- S
      hydroxyeicosatetraenoic acids (HETE) to modulate macrophage plasticity and
      cardiac fibroblast phenotype in presence or absence of lipid metabolizing enzyme
      12/15-lipoxygenase (LOX). Peritoneal macrophages and cardiac fibroblasts were
      isolated from wild-type (C57BL/6J) and 12/15LOX -/- mice and treated with DHA,
      LA, 12(S)-HETE, and RvD1 for 4, 8, 12, and 24 hr. LA, DHA, 12(S)-HETE, and RvD1
      elicited mRNA expression of proinflammatory markers; tumor necrosis factor-alpha
      ( Tnf-alpha), interleukin 6 ( IL-6), chemokine (C-C motif) ligand 2  (Ccl2), and
      IL-1beta in wild type (WT) and in 12/15LOX -/- macrophages at early time point (4
      hr). Bioactive immunoresolvent RvD1 lowered the levels of Tnf-alpha, IL-6, and IL
      1beta at 24 hr time point. Both DHA and RvD1 stimulated the proresolving markers
      such as arginase 1 ( Arg-1), chitinase-like protein 3 ( Ym-1), and mannose
      receptor C-type 1 in WT macrophage. RvD1 induced proresolving phenotype Arg-1
      expression in both WT 12/15LOX -/- macrophages even in presence of 12(S)-HETE.
      RvD1 peaked 5LOX expression in both WT and 12/15LOX -/- at 24 hr time point
      compared with DHA. RvD1 diminished cyclooxygenase-2 but upregulated 5LOX
      expression in fibroblast compared with DHA. In summary, the feed-forward
      enzymatic interaction with fatty acids substrates and direct mediators (RvD1 and
      12(S)-HETE) are responsive in determining macrophages phenotype and cardiac
      fibroblast plasticity. Particularly, macrophages and fibroblast phenotypes are
      responsive to milieu and RvD1 governs the milieu-dependent chemokine signaling in
      presence or absence of 12/15LOX enzyme to resolve inflammation.

PMID- 30191991
TI  - Potential therapeutic effects of curcumin in gastric cancer.
AB  - Despite recent advancements in understanding of the biology of gastric cancer,
      treatment of patients with advanced gastric cancer remains a major problem. Among
      different type of phytochemicals, curcumin, a welltable -known phytochemical, has
      been shown to be a promising cancer chemopreventive agent. Pharmacokinetics,
      safety, and efficacy of curcumin have been evaluated in several clinical trials
      against numerous diseases, and for the treatment of human cancer. In the present
      review, we have collected in vitro and in vivo investigations and studied the
      chemosensitizing and anticancer effects of curcumin against the gastric cancer
      cells. In summary, curcumin has been found to have efficient chemosensitizing
      effect and also inhibits viability, proliferation, and migration of gastric
      cancer cells mainly via cell cycle arrest and induction of apoptosis by both
      mitochondrial-dependent and -independent pathways.

PMID- 30191992
TI  - Matrix metalloproteinase-13 is a target gene of high-mobility group box
      containing protein 1 in modulating oral cancer cell invasion.
AB  - Transcription factor high-mobility group box-containing protein 1 (HBP1) may
      function as a tumor suppressor in various types of cancer. In a previous study,
      we demonstrated that HBP1 suppressed cell invasion in oral cancer. To further
      understand the underlying mechanism, the current study is aimed at investigating
      how HBP1 exerts its antimetastatic potential in oral cancer. In a cell model,
      ectopic expression of HBP1 potently suppressed epithelial-mesenchymal transition,
      cellular migration, and invasion; conversely, HBP1 knockdown promoted these
      malignant phenotypes. The matrix metalloproteinase (MMP) family is highly
      implicated in tumor metastasis. Therefore, we examined the effect of HBP1 on the
      activation of the MMP members, MMP-2, -9, and -13 that are highly associated with
      the aggressiveness of oral cancer. Ectopic expression of HBP1 resulted in a mild
      reduction in the expression and activity of MMP-2 and -9, yet it had a potent
      inhibitory effect on MMP-13. In contrast, HBP1 knockdown strongly enhanced the
      activation of MMP-13. Further, we demonstrated that MMP-13 is a target of HBP1
      transcription repression as evidenced by the identification of an HBP1 binding
      site in the cis proximal region of the MMP-13 promoter. More important, MMP-13
      knockdown significantly alleviated HBP1 small interfering RNA-mediated promotion
      in cell invasion. Analysis of oral tumor specimens revealed that the low HBP1
      (<0.3-fold)/high MMP-13 (>3-fold) status was associated with metastatic
      potential. All told, our study provides evidence supporting the idea that the
      HBP1-MMP-13 axis is a key regulator of the aggressiveness in oral cancer.

PMID- 30191993
TI  - 8-Br-cADPR, a TRPM2 ion channel antagonist, inhibits renal ischemia-reperfusion
      injury.
AB  - The transient receptor potential melastatin-2 (TRPM2) channel belongs to the
      transient receptor potential channel superfamily and is a cation channel
      permeable to Na+ and Ca 2+ . The TRPM2 ion channel is expressed in the kidney and
      can be activated by various molecules such as hydrogen peroxide, calcium, and
      cyclic adenosine diphosphate (ADP)-ribose (cADPR) that are produced during acute
      kidney injury. In this study, we investigated the role of 8-bromo-cyclic ADP
      ribose (8-Br-cADPR; a cADPR antagonist) in renal ischemia-reperfusion injury
      using biochemical and histopathological parameters. CD38, cADPR, tumor necrosis
      factor-alpha, interleukin-1beta, and myeloperoxidase (inflammatory markers), urea
      and creatinine, hydrogen peroxide (oxidant), and catalase (antioxidant enzyme)
      levels that increase with ischemia-reperfusion injury decreased in the groups
      treated with 8-Br-cADPR. In addition, renin levels were elevated in the groups
      treated with 8-Br-cADPR. Histopathological examination revealed that 8-Br-cADPR
      reduced renal damage and the expression of caspase-3 and TRPM2. Our results
      suggest that the inhibition of TRPM2 ion channel may be a new treatment modality
      for ischemic acute kidney injury.

PMID- 30191994
TI  - Therapeutic potency of pharmacological adenosine receptors agonist/antagonist on
      cancer cell apoptosis in tumor microenvironment, current status, and
      perspectives.
AB  - The hypoxic niche of tumor leads to a tremendous increase in the extracellular
      adenosine concentration through alteration of adenosine metabolism in the tumor
      microenvironment (TME). This consequently affects cancer progression, local
      immune responses, and apoptosis of tumor cells. Regulatory effect of adenosine on
      apoptosis in TME depends on the cancer cell type, pharmacological characteristics
      of adenosine receptor subtypes, and the adenosine concentration in the tumor
      niche. Exploiting specific pharmacological adenosine receptor agonist and
      antagonist inducing apoptosis in cancer cells can be considered as a proper
      procedure to control cancer progression. This review summarizes the regulatory
      role of adenosine in cancer cell apoptosis for a better understanding, and hence
      better management of the disease.

PMID- 30191995
TI  - The efficacy of metformin compared with insulin in regulating blood glucose
      levels during gestational diabetes mellitus: A randomized clinical trial.
AB  - BACKGROUND: Insulin has been a conventional medication in the treatment of female
      patients suffering from gestational diabetes mellitus (GDM). However, the need
      for a large number of insulin injections in these patients causes them a lot of
      discomforts. Recently, an alternative medication, metformin, has received
      considerable attention in the treatment of GDM. The aim of this study was to
      compare the efficacy of metformin and insulin in regulating blood glucose levels
      and fetal outcomes in GDM. METHODS: This randomized clinical trial included 286
      pregnant women diagnosed with positive GDM at 24-28 weeks of pregnancy. The
      subjects were randomly divided into two groups of 143 patients, with one group
      receiving insulin and the other undergoing a treatment plan using metformin.
      Fasting plasma glucose (FPG), 2-hr plasma glucose (PG) and glycated hemoglobin
      (HbA1c) were recorded twice a month until delivery. Other variables, including
      birth delivery method, cause of cesarean section, gestational age at the delivery
      time, birth trauma, Apgar score, birth weight, admission at neonatal intensive
      care unit (NICU), and neonatal hypoglycemia were also registered. RESULTS: Age of
      mother, body mass index, history of diabetes in the family, previous history of
      GDM, parity, FPG, 1- and 2-hr PG after meals, and 75-g glucose tolerance test
      before treatment were not statistically different between the two groups. FPG,
      PG, and HbA1c did not show significant differences between the two groups after
      completing the course of treatment. There was also no significant difference
      between two groups regarding the birth delivery method, the cause of cesarean
      section, birth trauma, Apgar score, birth weight, admission at NICU, and neonatal
      hypoglycemia. CONCLUSION: As mean FPG and 2-hr PG were not significantly
      different between the two groups, it seems that metformin can be recommended as
      an effective substitute for insulin in the treatment of GDM. However, there are
      still some undesirable risk factors with both treatments that may threaten the
      mother and the newborn.

PMID- 30191996
TI  - PD-1/PD-L1 immune checkpoint: Potential target for cancer therapy.
AB  - Recent studies show that cancer cells are sometimes able to evade the host
      immunity in the tumor microenvironment. Cancer cells can express high levels of
      immune inhibitory signaling proteins. One of the most critical checkpoint
      pathways in this system is a tumor-induced immune suppression (immune checkpoint)
      mediated by the programmed cell death protein 1 (PD-1) and its ligand, programmed
      death ligand 1 (PD-L1). PD-1 is highly expressed by activated T cells, B cells,
      dendritic cells, and natural killer cells, whereas PD-L1 is expressed on several
      types of tumor cells. Many studies have shown that blocking the interaction
      between PD-1 and PD-L1 enhances the T-cell response and mediates antitumor
      activity. In this review, we highlight a brief overview of the molecular and
      biochemical events that are regulated by the PD-1 and PD-L1 interaction in
      various cancers.

PMID- 30191997
TI  - Antioxidative potential of antidiabetic agents: A possible protective mechanism
      against vascular complications in diabetic patients.
AB  - Many vascular complications are related to exposure of tissues to elevated levels
      of glucose, a condition that promotes oxidative stress. The primary goal of
      antidiabetic medication is for normalization of blood glucose. However,
      antidiabetic medications may have antioxidant effects that go beyond their
      hypoglycemic influences. Therefore, antidiabetic drugs may be doubly beneficial
      in preventing diabetic complications. Vascular dysfunction due to uncontrolled
      diabetes is a serious complication of the disease and one which has a severe
      impact on quality of life. Readjustment of the oxidative balance in subjects with
      diabetes, and the positive effects thereof is a topic of intense interest at
      present. In the current review, we highlight the antioxidant effects of
      antidiabetic medications which may prevent or delay the onset of vascular
      dysfunction.

PMID- 30191998
TI  - Recovery from hypoxia-induced internalization of cardiac Na+ /H + exchanger 1
      requires an adequate intracellular store of antioxidants.
AB  - The heart is highly active metabolically but relatively underperfused and,
      therefore, vulnerable to ischemia. In addition to acidosis, a key component of
      ischemia is hypoxia that can modulate gene expression and protein function as
      part of an adaptive or even maladaptive response. Here, using cardiac-derived HL
      1 cells, we investigate the effect of various hypoxic stimuli on the expression
      and activity of Na+ /H + exchanger 1 (NHE1), a principal regulator of
      intracellular pH. Acute (10 min) anoxia produced a reversible decrease in the
      sarcolemmal NHE1 activity attributable to NHE1 internalization. Treatment with
      either 1% O 2 or dimethyloxaloylglycine (DMOG; 1 mM) for 48-hr stabilized hypoxia
      inducible factor 1 and reduced the sarcolemmal NHE1 activity by internalization,
      but without a change in total NHE1 immunoreactivity or message levels of the
      coding gene ( SLC9A1) determined in whole-cell lysates. Unlike the effect of
      DMOG, which was rapidly reversed on washout, reoxygenation after a prolonged
      period of hypoxia did not reverse the effects on NHE1, unless media were also
      supplemented with a membrane-permeant derivative of glutathione (GSH). Without a
      prior hypoxic episode, GSH supplementation had no effect on the NHE1 activity.
      Thus, posthypoxic NHE1 reinsertion can only take place if cells have a sufficient
      reservoir of a reducing agent. We propose that oxidative stress under prolonged
      hypoxia depletes intracellular GSH to an extent that curtails NHE1 reinsertion
      once the hypoxic stimulus is withdrawn. This effect may be cardioprotective, as
      rapid postischaemic restoration of the NHE1 activity is known to trigger
      reperfusion injury by producing an intracellular Na + -overload, which is
      proarrhythmogenic.

PMID- 30191999
TI  - Photophysical properties of Na+ -indicator dyes suitable for quantitative two
      photon fluorescence-lifetime measurements.
AB  - : Two-photon microscopy (2PM) offers great potential in fluorescence imaging of
      intracellular Na+ dynamics of live cells. A severe drawback, however, is that
      quantitative ratioing of fluorescence intensities at different wavelengths
      [possible in one-photon imaging with the classical Na+ -indicator dye sodium
      binding benzofuran isophtalate (SBFI)] is not practical in 2PM. We aimed at
      establishing 2PM-based time-correlated fluorescence lifetime measurements as an
      alternative method for quantifying Na+ dynamics. We compared the photophysical
      properties of the four Na+ -sensitive fluorescent indicator dyes SBFI, CoroNa
      Green, Sodium Green and Asante NaTRIUM Green-2 (ANG-2) in cuvette calibrations.
      All four dyes showed Na+ -dependent intensity changes, with ANG-2 having the most
      favourable properties for 2PM. All dyes but SBFI showed significant changes in
      their fluorescence lifetime upon Na+ binding, again with ANG-2 being the most
      promising dye. We found that, unfortunately, the fluorescence lifetime of ANG-2
      is not only affected by Na+ but also by protons, K+ and dye impurities, rendering
      a quantitative description of the individual lifetime components impractical.
      However, a simplified calibration procedure, based on a published approach for
      Ca2+ imaging, allowed relating lifetimes to Na+ concentration. Using ANG-2 and
      the simplified calibration will allow quantitative two-photon Na+ imaging with
      millimolar sensitivity. LAY DESCRIPTION: Dynamic changes of ion concentrations,
      which play crucial roles in cellular physiology, can be monitored with
      appropriate fluorescent indicator dyes. For intracellular sodium ions (Na+ ),
      certain dyes even allow quantitative measurements with standard microscopic
      techniques. However, for two-photon microscopy, which allows resolving cells deep
      in intact tissue, imaging solutions that are fully quantitative are lacking. For
      the four commercially available Na+ dyes 'SBFI', 'CoroNa Green', 'Sodium Green',
      and 'Asante NaTRIUM Green-2' (ANG2) we analyzed whether their fluorescent
      lifetime (LT), i.e., the nanosecond decay of emission of photons after a pulsed
      excitation, could serve as a quantitative measure of intracellular Na+ . Pulsed
      excitation in the femtosecond range is an inherent feature of two-photon
      microscopy and, in combination with fast, single-photon counting microscopes,
      allows for easy-to-implement LT microscopy. We found that Sodium Green and ANG2
      showed strong Na+ -dependent changes in the fluorescence LT, while SBFI showed
      no, and CoroNa Green only small changes. ANG2, as the brightest dye, was further
      characterized regarding effects of protons and potassium ions (K+ ), both also
      present in cells at significant concentrations, on the fluorescence LT. We found
      that the LT of ANG2 is affected in a predictable manner by Na+ , K+ , and
      protons. However, our data reveal that the commercial dye must also contain
      impurities with unexpected Na+ - and K+ -binding characteristics, rendering a
      quantitative description of the individual lifetime components impractical. We,
      therefore, adapted a simplified calibration procedure, based on a published
      approach for Ca2+ imaging, that allows relating the average lifetime to Na+
      concentration. With this simplified calibration procedure, ANG2 is well suited
      for quantitative two-photon Na+ imaging with millimolar sensitivity.

PMID- 30192000
TI  - The essential chloroplast ribosomal protein uL15c interacts with the chloroplast
      RNA helicase ISE2 and affects intercellular trafficking through plasmodesmata.
AB  - Chloroplasts retain part of their ancestral genomes and the machinery for
      expression of those genomes. The nucleus-encoded chloroplast RNA helicase
      INCREASED SIZE EXCLUSION LIMIT2 (ISE2) is required for chloroplast ribosomal RNA
      processing and chloro-ribosome assembly. To further elucidate ISE2's role in
      chloroplast translation, two independent approaches were used to identify its
      potential protein partners. Both a yeast two-hybrid screen and a pull-down assay
      identified plastid ribosomal protein L15, uL15c (formerly RPL15), as interacting
      with ISE2. The interaction was confirmed in vivo by co-immunoprecipitation.
      Interestingly, we found that rpl15 null mutants do not complete embryogenesis,
      indicating that RPL15 is an essential gene for autotrophic growth of Arabidopsis
      thaliana. Arabidopsis and Nicotiana benthamiana plants with reduced expression of
      RPL15 developed chlorotic leaves, had reduced photosynthetic capacity and
      exhibited defective chloroplast development. Processing of chloroplast ribosomal
      RNAs and assembly of ribosomal subunits were disrupted by reduced expression of
      RPL15. Chloroplast translation was also decreased, reducing accumulation of
      chloroplast-encoded proteins, in such plants compared to wild-type plants.
      Notably, knockdown of RPL15 expression increased intercellular trafficking, a
      phenotype also observed in plants with reduced ISE2 expression. This finding
      provides further evidence for chloroplast function in modulating intercellular
      trafficking via plasmodesmata.

PMID- 30192001
TI  - Adjuvant chemotherapy with melatonin for targeting human cancers: A review.
AB  - Melatonin is a multifunctional hormone that has long been known for its
      antitumoral effects. An advantage of the application of melatonin in cancer
      therapy is its ability to differentially influence tumors from normal cells. In
      this review, the roles of melatonin adjuvant therapy in human cancer are
      discussed. Combination of melatonin with chemotherapy could provide synergistic
      antitumoral outcomes and resolve drug resistance in affected patients. This
      combination reduces the dosage for chemotherapeutic agents with the subsequent
      attenuation of side effects related to these drugs on normal cells around tumor
      and on healthy organs. The combination therapy increases the rate of survival and
      improves the quality of life in affected patients. Cancer cell viability is
      reduced after application of the combinational melatonin therapy. Melatonin does
      all these functions by adjusting the signals involved in cancer progression, re
      establishing the dark/light circadian rhythm, and disrupting the redox system for
      cancer cells. To achieve effective therapeutic outcomes, melatonin concentration
      along with the time of incubation for this indoleamine needs to be adjusted.
      Importantly, a special focus is required to be made on choosing an appropriate
      chemotherapy agent for using in combination with melatonin. Because of different
      sensitivities of cancer cells for melatonin combination therapy, cancer-specific
      targeted therapy is also needed to be considered. For this review, the PubMed
      database was searched for relevant articles based on the quality of journals, the
      novelty of articles published by the journals, and the number of citations per
      year focusing only on human cancers.

PMID- 30192002
TI  - The immunomodulatory role of probiotics in allergy therapy.
AB  - The increased incidence of allergic disorders may be the result of a relative
      fall in microbial induction in the intestinal immune system during infancy and
      early childhood. Probiotics have recently been proposed as viable microorganisms
      for the prevention and treatment of specific allergic diseases. Different
      mechanisms have been considered for this probiotic property, such as generation
      of cytokines from activated pro-T-helper type 1 after bacterial contact. However,
      the effects of its immunomodulatory potential require validation for clinical
      applications. This review will focus on the currently available data on the
      benefits of probiotics in allergy disease.

PMID- 30192003
TI  - Long noncoding RNA H19 participates in metformin-mediated inhibition of gastric
      cancer cell invasion.
AB  - Recent research suggests that the first-line oral antidiabetes drug metformin may
      prevent gastric cancer progression and improve prognosis. Many studies have also
      shown that long noncoding RNAs (lncRNAs) play important roles in many biological
      processes. Therefore, we aimed to explore whether lncRNAs participate in the
      mechanisms by which metformin affects gastric cancer cells. In the current study,
      we found that metformin significantly inhibited the cellular functions of gastric
      cancer cells through Cell Counting Kit-8 and invasion assays. We found that
      lncRNA H19 was greatly downregulated in gastric cancer cells treated with
      metformin using lncRNA microassays. Based on bioinformatics analyses of the
      Oncomine and The Cancer Genome Atlas databases, H19 is shown to be overexpressed
      in gastric cancer tissues, with increased expression of H19 relating to advanced
      pathological tumor stage and pathological tumor node metastasis stage, indicating
      that H19 may be associated with the invasive ability of gastric cancer. We
      knocked down H19 in AGS and SGC7901 cell lines and found that knocked-down H19
      could decrease gastric cancer cell invasion and that metformin could not further
      decrease invasion after the knock down. Moreover, H19 depletion increased AMPK
      activation and decreased MMP9 expression, and metformin could not further
      activate AMPK or decrease MMP9 in H19 knocked-down gastric cancer cells. In
      summary, metformin has a profound antitumor effect on gastric cancer cells, and
      H19 is a key component in the process of metformin suppressing gastric cancer
      cell invasion.

PMID- 30192004
TI  - Adipocyte biology: It is time to upgrade to a new model.
AB  - Globally, the obesity pandemic is profoundly affecting quality of life and
      economic productivity, but efforts to address this, especially on a
      pharmacological level, have generally proven unsuccessful to date, serving as a
      stark demonstration that our understanding of adipocyte biology and
      pathophysiology is incomplete. To deliver better insight into adipocyte function
      and obesity, we need improved adipocyte models with a high degree of fidelity in
      representing the in vivo state and with a diverse range of experimental
      applications. Adipocyte cell lines, especially 3T3-L1 cells, have been used
      extensively over many years, but these are limited in terms of relevance and
      versatility. In this review, I propose that primary adipose-derived stromal/stem
      cells (ASCs) present a superior model with which to study adipocyte biology ex
      vivo. In particular, ASCs afford us the opportunity to study adipocytes from
      different, functionally distinct, adipose depots and to investigate, by means of
      in vivo/ex vivo studies, the effects of many different physiological and
      pathophysiological factors, such as age, body weight, hormonal status, diet and
      nutraceuticals, as well as disease and pharmacological treatments, on the biology
      of adipocytes and their precursors. This study will give an overview of the
      characteristics of ASCs and published studies utilizing ASCs, to highlight the
      areas where our knowledge is lacking. More comprehensive studies in primary ASCs
      will contribute to an improved understanding of adipose tissue, in healthy and
      dysfunctional states, which will enhance our efforts to more successfully manage
      and treat obesity.

PMID- 30192005
TI  - His-bundle pacing as a standard approach in patients with permanent atrial
      fibrillation and bradycardia.
AB  - BACKGROUND: His-bundle (HB) pacing is the most physiological method of
      ventricular pacing. However, it is also considered a demanding procedure with a
      low success rate and has suboptimal pacing parameters. There is a scarcity of
      data concerning HB pacing as a standard approach in patients with symptomatic
      bradycardia. Our goal was to compare acute and chronic results of two approaches
      to pacing in patients with permanent atrial fibrillation, narrow QRS complexes,
      and symptomatic bradycardia: right ventricular myocardial pacing versus HB
      pacing. METHODS: Consecutive patients who received HB pacemakers were compared
      with historical controls-i.e., consecutive patients with classic VVI pacemaker
      implantations, performed by the same operator before 2014 (commencement of
      routine HB implantations). Acute and long-term capture threshold, sensing,
      battery current drain, as well as procedure and fluoroscopy duration,
      complications, and success rate were compared. RESULTS: One hundred and twenty
      five patients were analyzed (including 65 patients with HB pacing): age 73.0 +/-
      10.5 years, left ventricular ejection fraction of 48.2 +/- 13.5%. HB pacing was
      inferior to right ventricular myocardial pacing in terms of higher threshold,
      lower sensing amplitude, higher current drain, lower success rate, longer
      procedure, and fluoroscopy times. However, despite this, HB procedure and
      fluoroscopy times of 64.4 +/- 30.0 and 11.0 +/- 10.7 minutes, respectively, long
      term successful HB pacing in 87.9% of patients, a chronic threshold of 1.5 +/-
      1.1 V, chronic sensing of 3.6 +/- 2.5 mV, and chronic current drain per pulse of
      3.4 +/- 4.4 MUAh seem acceptable. CONCLUSIONS: HB pacing can be used as an
      alternative standard method of pacing in atrial fibrillation patients.

PMID- 30192006
TI  - Comparative study of interruption of signaling pathways in lung epithelial cell
      by two different Mycobacterium tuberculosis lineages.
AB  - Alveolar epithelial cell (AEC) provides a replication niche for Mycobacterium
      tuberculosis. Based on the role of AEC in M. tuberculosis pathogenesis and
      existence of genetic diversity within this bacterium, we investigated
      interactions between AEC II and two different M. tuberculosis lineages. We have
      compared the transcriptome and cytokines/chemokines levels of A549 infected by M.
      tuberculosis lineage three and four using qRT-PCR and ELISA arrays, respectively.
      We showed different M.  tuberculosis strains induced changes in different
      effectors that involved in TLRs and NF-kappaB signaling pathways. We observed
      different reaction of the studied lineages specifically in pathogenesis, immune
      evasion mechanism, IL-12/IFN-gamma axis, and autophagy. Similar behavior was
      detected in regarding to apoptosis, necroptosis, anti-inflammatory responses, and
      canonical inflammasome. Our findings contribute to elucidate more details in
      pathogenesis, immune evasion strategies, novel target and druggable pathway for
      therapeutic intervention, and host directed therapy in tuberculosis infection.
      Also, different M.  tuberculosis lineages-dependent host-pathogen interactions
      suggested using only one strain for this kind of research will be controversial.

PMID- 30192008
TI  - PI3k/AKT signaling pathway: Erythropoiesis and beyond.
AB  - Erythropoiesis is a multi-step process that involves the differentiation of
      hematopoietic stem cells into mature red blood cells (RBCs). This process is
      regulated by several signaling pathways, transcription factors and microRNAs
      (miRNAs). Many studies have shown that dysregulation of this process can lead to
      hematologic disorders. PI3K/AKT is one of the most important pathways that
      control many cellular processes including, cell division, autophagy, survival,
      and differentiation. In this review, we focus on the role of PI3K/AKT pathway in
      erythropoiesis and discuss the function of some of the most important genes,
      transcription factors, and miRNAs that regulate different stages of
      erythropoiesis which play roles in differentiation and maturation of RBCs,
      prevention of apoptosis, and autophagy induction. Understanding the role of the
      PI3K pathway in erythropoiesis may provide new insights into diagnosing
      erythrocyte disorders.

PMID- 30192009
TI  - Withdrawal of oral anticoagulants 3 months after successful radiofrequency
      catheter ablation in patients with atrial fibrillation: A meta-analysis.
AB  - BACKGROUND: The best anticoagulation therapy for atrial fibrillation (AF) after
      radiofrequency catheter ablation (RFCA) remains a challenge. METHODS: A
      systematic search of PubMed, Ovid, and Cochrane Library was conducted identifying
      at clinical trials which evaluated the differences between thromboembolism (TE)
      and hemorrhage in an off-oral anticoagulants (OACs) treatment group (the
      observation group) and an on-OACs treatment group (the control group), at 3
      months after successful RFCA. Meta-analysis was performed using RevMan 5.3
      software, and the fixed effect model was used as a relevant statistical model.
      chi2 test and I2 were used to test for the presence of heterogeneity. Subgroup
      analysis and sensitivity analysis were also performed. RESULTS: The results
      showed no significant differences between two groups in TE (relative risk [RR]
      0.82, 95% confidence interval [CI], 0.51-1.33, P = 0.42), and only mild
      heterogeneity (P = 0.22, I2  = 29%). No significant differences in TE between two
      subgroups were found according to < 3 years and >= 3 years follow-up analyses (RR
      0.58, 95% CI, 0.26-1.28, P = 0.18; RR 1.00, 95% CI, 0.54-1.85, P = 1.00).
      Furthermore, there was a lower risk of TE in the observation subgroup (< 60
      years) compared to the control group (RR 0.31, 95% CI, 0.12-0.78, P = 0.01).
      Also, there were no significant differences in TE between two subgroups (>= 60
      years, RR 1.24, 95% CI, 0.67-2.28, P = 0.49). The risk of hemorrhage in the
      observation group was significantly lower compared to the control group (RR 0.05,
      95%CI, 0.02-0.14, P < 0.00001). CONCLUSIONS: The withdrawal of OACs 3 months
      after successful radiofrequency catheter ablation for patients with AF may be
      safe and feasible. It needs to be tested by randomized controlled trial.

PMID- 30192010
TI  - Structural basis of urea-induced unfolding of Fasciola gigantica glutathione S
      transferase.
AB  - Glutathione S-transferases (GSTs) are enzymes that are involved in the
      detoxification of harmful electrophilic endogenous and exogenous compounds by
      conjugating with glutathione (GSH). The liver fluke GSTs have multifunctional
      roles in the host-parasite interaction, such as general detoxification and bile
      acid sequestration to synthase activity. The GSTs have been highlighted as
      vaccine candidates towards parasitic flukes. In this study, we have thoroughly
      examined the urea-induced unfolding of a mu-class Fasciola gigantica GST1
      (FgGST1) using spectroscopic techniques and molecular dynamic simulations. FgGST1
      is a highly cooperative molecule, because during urea-induced equilibrium
      unfolding, a concurrent unfolding of the protein without stabilization of any
      folded intermediate was observed. The protein was stabilized with conformational
      free energy of about ~12.36 kcal/mol. The protein loses its activity with
      increasing urea concentration, as the GSH molecule is not able to bind to the
      protein. We also studied the fluorescence quenching of Trp residues and the
      obtained K SV data that provided additional information on the unfolding of
      FgGST1. Molecular dynamic trajectories simulated in different urea concentrations
      and temperatures indicated that urea destabilizes FgGST1 structure by weakening
      hydrophobic interactions and the hydrogen bond network. We observed a precise
      correlation between the in vitro and in silico studies.

PMID- 30192007
TI  - Rasagiline for amyotrophic lateral sclerosis: A randomized, controlled trial.
AB  - INTRODUCTION: Rasagiline is a monoamine oxidase B (MAO-B) inhibitor with possible
      neuroprotective effects in patients with amyotrophic lateral sclerosis (ALS).
      METHODS: We performed a randomized, double-blind, placebo-controlled trial of 80
      ALS participants with enrichment of the placebo group with historical controls (n
      = 177) at 10 centers in the United States. Participants were randomized in a 3:1
      ratio to 2 mg/day rasagiline or placebo. The primary outcome was average slope of
      decline on the ALS Functional Rating Scale-Revised (ALSFRS-R). Secondary measures
      included slow vital capacity, survival, mitochondrial and molecular biomarkers,
      and adverse-event reporting. RESULTS: There was no difference in the average 12
      month ALSFRS-R slope between rasagiline and the mixed placebo and historical
      control cohorts. Rasagiline did not show signs of drug-target engagement in urine
      and blood biomarkers. Rasagiline was well tolerated with no serious adverse
      events. DISCUSSION: Rasagiline did not alter disease progression compared with
      controls over 12 months of treatment. Muscle Nerve, 2017.

PMID- 30192011
TI  - Using Ethylcellulose to Structure Oil Droplets in Ice Cream Made with High Oleic
      Sunflower Oil.
AB  - : In order to mimic physical characteristics of solid fat, ethylcellulose (EC)
      was used as an oleogelator in ice creams made with high oleic sunflower oil
      (HOSO). The aim was to improve structure of ice cream made with fully liquid
      vegetable oil by inhibiting droplet coalescence and to enable a colloidal fat
      network by making the oil droplets solid-like. Two different methods for
      incorporating EC into emulsions were developed, both designed to involve high
      pressure homogenization of ice cream mixes as in traditional ice cream
      production. Ice creams based on 10% HOSO and 1% EC (cP10 or cP20) were
      successfully made. Two types of emulsifiers in the ice cream formulations were
      tested: unsaturated monoglyceride (GMU) or saturated mono-diglyceride. GMU
      enhanced fat destabilization of ice cream resulting in coalescence of
      unstructured HOSO droplets. Presence of EC in HOSO based ice cream inhibited
      coalescence of oil droplets and the structure of the lipid phase resembled the
      small, evenly distributed fat globules in the reference ice cream made with
      saturated coconut fat. The resisting effect toward coalescence increased with
      higher molecular weight of EC, accordingly oil droplets made with EC cP20 were
      smaller compared to oil droplets containing EC cP10. EC did not increase the
      amount of air that was incorporated in ice creams based on HOSO, irrespective of
      the type of emulsifier. In general the overrun in HOSO-based ice creams (with and
      without EC) was considerably lower compared to ice cream made with coconut fat.
      PRACTICAL APPLICATION: Interest for product development of ice cream based on
      unsaturated liquid oil is increasing. To compensate for the lacking fat crystals
      that provide structure and stability in traditional ice cream, the liquid oil is
      transformed into solid-like material by ethylcellulose (EC). The process of ice
      cream includes high pressure homogenization, and in order to adapt to this
      process step, two new methods of incorporation of EC into the oil of ice cream
      mixes were developed.

PMID- 30192012
TI  - Luteolin attenuates glucocorticoid-induced osteoporosis by regulating ERK/Lrp
      5/GSK-3beta signaling pathway in vivo and in vitro.
AB  - Glucocorticoid-induced osteoporosis (GIO) is a secondary osteoporosis with
      extensive use of glucocorticoids (GCs). GCs can increase bone fragility and
      fracture via inhibiting osteoblastic proliferation and differentiation. Luteolin
      (LUT), a kind of plant flavonoid, has been reported to exhibit the antioxidant
      activity, but the effects of LUT on GIO still remain unclear. This study aimed to
      investigate the effects of LUT on GIO both in vivo and in vitro and elaborate the
      potential molecular mechanisms. LUT increased the superoxide dismutase activity,
      glutathione level and decreased reactive oxygen species (ROS) level and lactate
      dehydrogenase release in GIO. Meanwhile, LUT decreased caspase-3, caspase-9, and
      Bax protein expressions and increased Bcl-2 protein expression in GIO. LUT
      increased the ratio of osteoprotegerin (OPG)/receptor activator of nuclear factor
      kappaB Ligand (RANKL) messenger RNA (mRNA) expression and mRNA expression levels
      of osteogenic markers, including runt-related transcription factor 2, osterix,
      collagen type I, and osteocalcin. LUT also enhanced the extracellular signal
      regulated kinases (ERK) phosphorylation, glycogen synthase kinase 3beta (GSK
      3beta) phosphorylation, mRNA expression levels of lipoprotein-receptor-related
      protein 5 (Lrp-5) and beta-catenin. Further study revealed that Lrp-5 small
      interfering RNA (siRNA )and ERK-siRNA reduced the effects of LUT on GSK-3beta
      phosphorylation, alkaline phosphatase (ALP) activity and the ratio of OPG/RANKL
      mRNA expression. Moreover, ERK-siRNA decreased Lrp-5 mRNA expression in vitro.
      These results indicated that LUT promoted proliferation by attenuating oxidative
      stress and promoted osteoblastic differentiation by regulating the ERK/Lrp-5/GSK
      3beta pathway in GIO. This study may bring to light the possible mechanisms
      involved in the action of LUT in GIO treatment, and benefit for further research
      on GIO.

PMID- 30192013
TI  - Aplysin Protects Against Alcohol-Induced Liver Injury Via Alleviating Oxidative
      Damage and Modulating Endogenous Apoptosis-Related Genes Expression in Rats.
AB  - : We investigated the protective effects and possible mechanisms of Aplysin
      against alcohol-induced liver injury. Rats were given daily either alcohol only
      (alcohol model group; 8 to 12 mL/kg body weight), one of three doses of Aplysin
      (50, 100, or 150 mg/kg Aplysin) plus alcohol, or volume-matched saline. After 6
      weeks, the effects of Aplysin were assessed in terms of changes in histology,
      biochemical indices, and DNA oxidative damage. Potential mechanisms were analyzed
      through measurements of lipid peroxidation, antioxidant defense systems,
      expression of cytochrome P450 2E1, and expression of apoptosis-related genes. We
      found that Aplysin significantly protected the liver against alcohol-induced
      oxidative injury, evidenced by improved hepatic histological structure, inhibited
      alcohol-induced elevation of serum biochemical indices, attenuated extents of
      hepatocellular DNA damage. At a mechanistic level, Aplysin alleviated alcohol
      induced oxidative stress as illustrated by the revivification of erythrocyte
      membrane fluidity, the attenuation of glutathione depletion, the restoration of
      antioxidase activities, and reduced malondialdehyde overproduction. Furthermore,
      the mRNA levels of Bax, cytochrome c, and cytochrome P450 2E1 were significantly
      down-regulated, whereas those of Bcl-2 and caspase-9 and caspase-3 were markedly
      up-regulated. These findings suggest that Aplysin provides significant protection
      against alcohol-induced liver injury, possibly through alleviating oxidative
      damage and modulating endogenous apoptosis-related genes expression. PRACTICAL
      APPLICATION: Many natural components derived from alga have been used in the
      food, cosmetics, and biomedicine industries. Aplysin, a marine
      bromosesquiterpene, was extracted from the red alga Laurencia tristicha, which
      could effectively protect against alcohol-induced liver injury, might be a
      potential natural sources for preventing alcoholic liver damage.

PMID- 30192014
TI  - Timed function tests have withstood the test of time as clinically meaningful and
      responsive endpoints in duchenne muscular dystrophy.

PMID- 30192015
TI  - Iron Fortification of Spiced Vinegar in the Philippines.
AB  - : Despite existent fortification initiatives in the Philippines, approximately
      50% of the population still suffers from iron deficiency anemia (IDA), mainly in
      rural areas. Fortification of staple foods has been proved successful in China
      and Vietnam. Coconut spiced vinegar (SV) is an inexpensive, widely available, and
      culturally acceptable condiment in Filipino households; however, no technical
      evidence exists on its potential as fortification vehicle. This study aimed to
      physicochemically characterize and evaluate the consumer acceptability of SV
      fortified with ferrous sulfate (FS), ferrous fumarate (FF), or sodium iron
      ethylenediaminetetraacetate (NaFeEDTA) at 0.2 mg Fe/mL. Iron fortificants were
      added directly to SV, vortexed, and stored for analysis. A nonfortified SV served
      as a control. Physicochemical analyses (pH, titratable acidity, color, turbidity,
      and iron recovery) were conducted from 0 to 6 months postfortification. Consumer
      acceptability (9-point hedonic scale: color, appearance, aroma, sourness, and
      overall acceptability) was conducted using 1-month fortified vinegar in 96
      students and 27 women. Iron recovery of fortified samples was high and similar
      (>97%) after 3 days of fortification and remained >87% at 6 months
      postfortification. All samples had minimum acidity of 5.31% and pH between 3.12
      and 3.3. Color difference against the control followed the next order: SV
      NaFeEDTA < SV-FS = SV-FF. Among students, acceptability of SV-FS and SV-FF were
      lower than the control and SV-NaFeEDTA for all attributes (P < 0.05) except
      aroma. In women, overall acceptability and aroma were not different among samples
      (P > 0.05). Overall, SV-NaFeEDTA had similar acceptability to the control, and
      was the most accepted fortified vinegar. SV-NaFeEDTA shows potential (in terms of
      physicochemical stability and consumer acceptability) to be used as an iron
      delivery vehicle to address IDA. PRACTICAL APPLICATION: The present study
      addresses the technical and organoleptic challenges of fortifying Filipino spiced
      vinegar with three iron sources. About 50% of the Filipino population (especially
      women and children) still suffers from iron deficiency, thus, more effective ways
      to deliver iron are needed. If successful, our study could pose as the base
      milestone for implementing mass iron fortification of spiced vinegar, given its
      frequent consumption and reach of all socioeconomic pockets of the Filipino
      population. Our aim is to improve the overall nutritional health of at-risk
      populations, and our study is one step closer to achieve this goal.

PMID- 30192016
TI  - Nonmechanical and multiview 3D measurement microscope for workpiece with large
      slope and complex geometry.
AB  - : Due to the large slope and complex geometry, it is difficult to measure the
      three-dimensional parameters of cutting tools and drill bits by using general
      optical measurement method. A method that combines the multiview rotation
      scanning and nonmechanical focus variation by using a liquid lens is proposed in
      this paper. Firstly, the workpiece is rotated by using a rotation unit, and in
      every rotation position, a sequence of images of the workpiece are captured in
      the axial direction. Secondly, the relative degree of focus is measured for all
      pixels by using focus measure operators to obtain the depth value corresponding
      to each pixel. Thirdly, a multiview registration algorithm is designed to combine
      all the individual data sets at each rotation position into a whole three
      dimensional point cloud. Finally, the three-dimensional parameters of the rake
      angle and clearance angle of the gear, screw tap and drills are measured. The
      proposed method is lateral shift-free and no light intensity variation, so it can
      obtain better accuracy. The experimental results show that the accuracy of the
      axial measurement reaches 2.4 MUm (2sigma, Nikon 5*/0.1). LAY DESCRIPTION: This
      article is about a method that combines the multi-view rotation scanning and non
      mechanical focus variation by using a liquid lens.

PMID- 30192017
TI  - Optical coherence tomography evaluation of the optic nerve head neuro-retinal rim
      in glaucoma.
AB  - Clinical examination of the optic disc is a fundamental component of any
      ophthalmic evaluation, but it is especially important for diagnosis and
      management of glaucoma. The purpose of this article is to: (1) review the
      limitations inherent to clinical examination; (2) outline the rationale for
      adopting into clinical practice quantitative measures of the optic nerve head
      neuro-retinal rim tissue integrity derived from current optical coherence
      tomography imaging approaches; (3) describe recent developments in this area; and
      (4) highlight a few avenues of active research that hold promise for future
      translation to clinical practice.

PMID- 30192018
TI  - Ecopipam, a D1 receptor antagonist, for treatment of tourette syndrome in
      children: A randomized, placebo-controlled crossover study.
AB  - BACKGROUND: Dopamine D2 receptor antagonists used to treat Tourette syndrome may
      have inadequate responses or intolerable side effects. We present results of a 4
      week randomized, double-blind, placebo-controlled crossover study evaluating the
      safety, tolerability, and efficacy of the D1 receptor antagonist ecopipam in
      children and adolescents with Tourette syndrome. METHODS: Forty youth aged 7 to
      17 years with Tourette syndrome and a Yale Global Tic Severity Scale - total tic
      score of >=20 were enrolled and randomized to either ecopipam (50 mg/day for
      weight of <34 kg, 100 mg/day for weight of >34 kg) or placebo for 30 days,
      followed by a 2-week washout and then crossed to the alternative treatment for 30
      days. Stimulants and tic-suppressing medications were excluded. The primary
      outcome measure was the total tic score. Secondary outcomes included obsessive
      compulsive and attention deficit/hyperactivity disorder scales. RESULTS: Relative
      to changes in placebo, reduction in total tic score was greater for ecopipam at
      16 days (mean difference, -3.7; 95% CI, -6.5 to -0.9; P = 0.011) and 30 days
      (mean difference, -3.2; 95% CI, -6.1 to -0.3; P = 0.033). There were no weight
      gain, drug-induced dyskinesias, or changes in laboratory tests,
      electrocardiograms, vital signs, or comorbid symptoms. Dropout rate was 5% (2 of
      40). Adverse events reported for both treatments were rated predominantly mild to
      moderate, with only 5 rated severe (2 for ecopipam and 3 for placebo).
      CONCLUSIONS: Ecopipam reduced tics and was well tolerated. This placebo
      controlled study of ecopipam supports further clinical trials in children and
      adolescents with Tourette syndrome. (c) 2018 International Parkinson and Movement
      Disorder Society.

PMID- 30192019
TI  - Statins after intracranial haemorrhage: seizing a new opportunity?

PMID- 30192020
TI  - The fibronectin-binding protein homologue Fbp62 of Streptococcus anginosus is a
      potent virulence factor.
AB  - Streptococcus anginosus appears to be able to adhere to cultured epithelial cells
      or fibronectin and this may be associated with bacterial pathogenicity. In the
      present study, the molecular characteristics and virulence of the fibronectin
      binding protein (FBP), Fbp62, of S. anginosus were investigated in animal models
      to determine the role of the molecule in bacterial infection. fbp62 encodes a 549
      amino acid residue with an apparent molecular mass of 62.8 kDa that lacks a
      membrane anchor motif and a leader peptide, suggesting that fbp62 codes for an
      atypical FBP. It has been observed that the S. anginosus Fbp62 is very similar to
      the FbpA of Streptococcus gordonii, PavA of Streptococcus pneumoniae, SmFnB of
      Streptococcus mutans and Fbp54 of Streptococcus pyogenes. Recombinant Fbp62
      prepared from pGEX-4T-2 was found to bind to fibronectin in a dose-dependent
      manner and competitively inhibit the binding of S. anginosus to fibronectin.
      Furthermore, anti-Fbp62 antiserum abrogated the binding of S. anginosus to
      fibronectin. Adhesion of the isogenic mutant, Deltafbp62, constructed from S.
      anginosus NCTC 10713 (wild-type, WT) by homologous recombination to HEp-2 cells
      and DOK cells was significantly weaker than that of S. anginosus WT. In addition,
      Deltafbp62's lethality and ability to form abscesses were weaker in a mouse model
      of infection than in the WT strain. Taken together, these results suggest that
      Fbp62 is an important pathogenic factor of S. anginosus.

PMID- 30192021
TI  - Thinking of selection and widening access as complex and wicked problems.
AB  - OBJECTIVES: 'Wicked problems' are complex in nature, have innumerable causes
      associated with multiple social environments and actors with unpredictable
      behaviour and outcomes, and are difficult to define or even resolve. This paper
      considers why and how the frameworks of complexity theory and wicked problems can
      help medical educators consider selection and widening access (WA) to medicine
      through fresh eyes to guide future policy and practice. We illustrate how
      'wickedity' can frame the key issues in this area, and then address steps that
      education stakeholders might take to respond to and act on these issues. METHODS:
      We used the 10 properties of a wicked problem to frame common issues in the broad
      field of selection and WA in medicine. We drew heavily on literature from
      different disciplines, particularly education, and, through debate and
      reflection, agreed on the applicability of the theory for illuminating and
      potentially addressing outstanding issues in selection and WA. RESULTS: Framing
      medical school selection using the 10 properties of wicked problems is a means of
      shifting thinking from erroneous 'simple' solutions to thinking more contextually
      and receptively. The wicked problem framework positions selection as a multi
      causal, complex, dynamic, social problem and foregrounds stakeholders' views and
      context as being highly relevant in medical school selection. CONCLUSIONS: The
      wicked problem lens shifts thinking and action from seeking one elusive,
      objective truth to recognising the complexity of medical school selection,
      managing uncertainty, questioning and considering 'issues' associated with
      medical school selection more productively. Although there are criticisms of this
      framework, labelling medical selection as 'wicked' provides original insights and
      genuine reframing of the challenges of this important, and high profile, aspect
      of medical education. Doing so, in turn, opens the door to different responses
      than would be the case if selection and WA were simple and readily tamed.

PMID- 30192022
TI  - Proton pump inhibitors are not associated with inflammatory myopathies: A case
      control study.
AB  - INTRODUCTION: A rare association of proton pump inhibitor (PPI) use with the
      development of inflammatory myopathies (IM) has been reported, but, unlike with
      statin medications, there is limited data supporting or refuting this
      observation. METHODS: A case-control study was conducted on patients with IM.
      Clinical information, medications, and demographics were recorded. Controls were
      matched 3:1 for age and gender. RESULTS: Two hundred twenty-one cases of IM were
      identified. No association of PPI use with IM was observed when compared with
      controls (odds ratio 1.04 [95% confidence interval 0.68-1.58]) and similar
      results were observed after adjusting for diabetes, cardiovascular disease, and
      statin exposure (adjusted odds ratio 1.084 [95% confidence interval 0.69-1.70]).
      There was no association of any histologic subtype of IM with PPI exposure.
      DISCUSSION: Our findings do not support an association of PPI exposure with IM.
      Co-prescription of PPI with other medications was not considered and could be
      further investigated with larger cohorts. Muscle Nerve, 2018.

PMID- 30192023
TI  - Diagnostic framing of IgM monoclonal gammopathy: Focus on Waldenstrom
      macroglobulinemia.
AB  - The finding of an IgM monoclonal gammopathy often represents a diagnostic
      challenge. In fact, there are many pathological disorders associated with this
      condition, each of which has distinctive characteristics and requires specific
      clinical, instrumental, and laboratory assessments to set the appropriate
      treatment. This review has two aims. Firstly, to provide a framework of the broad
      spectrum of IgM-associated disorders: (1) monoclonal gammopathy of undetermined
      significance (MGUS); (2) Waldenstrom macroglobulinemia (WM); (3) IgM-related
      disorders (among which hyperviscosity syndrome, light chain amyloidosis, cold
      agglutinin disease, cryoglobulinaemia, IgM neuropathy, Polyneuropathy,
      organomegaly, endocrinopathy, monoclonal gammopathy, skin changes (POEMS)
      syndrome, Castleman disease); (4) IgM-secreting multiple myeloma (IgM-MM); and
      (5) other lymphoproliferative disorders which may be associated with IgM (such as
      chronic lymphocytic leukemia, small lymphocytic lymphoma, and B-cell non Hodgkin
      lymphoma). Secondly, to give a detailed insight regarding diagnosis and treatment
      of WM.

PMID- 30192024
TI  - Embracing the tension between vulnerability and credibility: 'intellectual
      candour' in health professions education.
AB  - The tension between expressing vulnerability and seeking credibility creates
      challenges for learning and teaching. This is particularly true in health care,
      in which practitioners are regarded as highly credible and making errors can
      often lead to dire consequences and blame. From a transformative learning
      perspective, expressing vulnerability may help individuals to access different
      ways of knowing. By contrast, from a sociological perspective, seeking to
      maintain credibility results in ritualised interactions and these ritualised
      encounters can reinforce credibility. One means of embracing this tension between
      expressing vulnerability and appearing credible is 'intellectual candour', an
      improvisational expression of doubts, thoughts and problems with the dual purpose
      of learning and promoting others' learning. Educators' revelations of inner
      struggles are proposed as a means of inviting reciprocal vulnerability. This
      builds trust and a platform for learning, particularly of the transformative
      nature. It also allows modelling of how to balance the vulnerability-credibility
      tension, which may provide a template for professional practice.

PMID- 30192026
TI  - Side effects of drugs for osteoporosis and metastatic bone disease.
AB  - Osteoporosis is a common condition that leads to substantial morbidity and
      mortality and affects an increasing number of persons worldwide. Several
      pharmacological therapies that inhibit bone resorption, promote bone formation,
      or both, are available for the treatment of osteoporosis. The osteoanabolic
      treatment spectrum was recently expanded by the introduction of a novel bone
      forming agent in the United States, and clinical trials indicate that a new class
      of bone anabolic therapy may become available. Both antiresorptive and bone
      anabolic therapies are associated with common and rare adverse effects, which are
      particularly important to address as these drugs are used for long-term treatment
      in numerous patients with a large proportion being elderly and/or having
      multimorbidity. In addition, antiresorptive drugs are used to inhibit bone
      resorption in patients with malignant hypercalcaemia or to prevent skeletal
      events in cancer patients, and bisphosphonates have been repurposed as a cancer
      preventive therapy. However, therapeutic doses are generally higher when
      antiresorptive drugs are used in the oncological setting, which influence the
      prevalence of adverse effects significantly. This review highlights key issues
      and controversies regarding adverse effects of currently available and emerging
      drugs used for osteoporosis and metastatic bone diseases.

PMID- 30192027
TI  - Stiff person syndrome with Anti-GAD65 antibodies within the national veterans
      affairs health administration.
AB  - INTRODUCTION: Stiff person syndrome (SPS) is a neurological disorder
      characterized by muscle rigidity primarily in the truncal muscles, commonly
      associated with autoantibodies to the glutamic acid-decarboxylase 65 kD receptor
      (GAD65). There is limited epidemiological information on patients with SPS.
      METHODS: We performed a retrospective case review using the National United
      States Veterans Affairs Health Administration electronic medical record system.
      We analyzed prevalence, demographics, disease characteristics, and treatment
      outcomes in SPS patients who were anti-GAD65 antibody positive. RESULTS: Fifteen
      patients met our criteria. Point prevalence was 2.06 per million, and period
      prevalence was 2.71 per million. Men to women ratio was 14:1. All patients
      benefitted from treatment with symptomatic antispasmodic agents. Ten of 15
      patients received intravenous immunoglobulin, with a majority demonstrating
      stable or improved modified Rankin scores. DISCUSSION: This investigation was a
      large North American epidemiological study of SPS with predominantly male
      patients. Symptomatic therapy was beneficial for most patients, with less clear
      sustained benefit of immunotherapy. Muscle Nerve, 2018.

PMID- 30192025
TI  - Rivaroxaban and macitentan can be coadministered without dose adjustment but the
      combination of rivaroxaban and St John's wort should be avoided.
AB  - AIMS: We assessed the potential mutual interaction of oral macitentan (cytochrome
      P450 (CYP) 3A4 substrate) at steady-state with single-dose oral rivaroxaban
      (CYP3A4 and P-glycoprotein substrate) and evaluated the effect of the CYP3A and P
      glycoprotein inducer St John's wort (SJW) on the pharmacokinetics of these drugs
      in healthy volunteers. METHODS: Twelve healthy volunteers completed this open
      label, monocentre, two-period, one-sequence phase I clinical trial. The
      pharmacokinetics of macitentan (10 mg) was assessed on study days 3 (single
      dose), 15 (steady-state), 16 (impact of rivaroxaban) and 29 (after induction by
      oral SJW), and of rivaroxaban on days 2 (single dose), 16 (impact of macitentan
      at steady-state) and 29 (after induction by SJW). Concurrently, we quantified
      changes of CYP3A activity using oral microdoses of midazolam (30 MUg). RESULTS:
      Rivaroxaban and macitentan did not significantly change the pharmacokinetics of
      each other. After induction with SJW, CYP3A activity increased by 272% and
      geometric mean ratios of macitentan AUC decreased by 48% and of Cmax by 45%.
      Concurrently, also geometric mean ratios of rivaroxaban AUC and Cmax decreased by
      25%. CONCLUSIONS: There is no evidence for a relevant pharmacokinetic interaction
      between macitentan and rivaroxaban suggesting that these two drugs can be
      combined without dose adjustment. SJW strongly increased CYP3A activity and
      substantially reduced rivaroxaban and macitentan exposure while estimated net
      endothelin antagonism only decreased by 20%, which is considered clinically
      irrelevant. The combination of SJW with rivaroxaban should be avoided.

PMID- 30192028
TI  - Pre- and post-puberty expression of genes and proteins in the uterus of Bos
      indicus heifers: the luteal phase effect post-puberty.
AB  - Progesterone signaling and uterine function are crucial in terms of pregnancy
      establishment. To investigate how the uterine tissue and its secretion changes in
      relation to puberty, we sampled tissue and uterine fluid from six pre- and six
      post-pubertal Brahman heifers. Post-pubertal heifers were sampled in the luteal
      phase. Gene expression of the uterine tissue was investigated with RNA
      sequencing, whereas the uterine fluid was used for protein profiling with mass
      spectrometry. A total of 4034 genes were differentially expressed (DE) at a
      nominal P-value of 0.05, and 26 genes were significantly DE after Bonferroni
      correction (P < 3.1 * 10-6 ). We also identified 79 proteins (out of 230
      proteins) that were DE (P < 1 * 10-5 ) in the uterine fluid. When we compared
      proteomics and transcriptome results, four DE proteins were identified as being
      encoded by DE genes: OVGP1, GRP, CAP1 and HBA. Except for CAP1, the other three
      had lower expression post-puberty. The function of these four genes
      hypothetically related to preparation of the uterus for a potential pregnancy is
      discussed in the context of puberty. All DE genes and proteins were also used in
      pathway and ontology enrichment analyses to investigate overall function. The DE
      genes were enriched for terms related to ribosomal activity. Transcription
      factors that were deemed key regulators of DE genes are also reported.
      Transcription factors ZNF567, ZNF775, RELA, PIAS2, LHX4, SOX2, MEF2C, ZNF354C,
      HMG20A, TCF7L2, ZNF420, HIC1, GTF3A and two novel genes had the highest
      regulatory impact factor scores. These data can help to understand how puberty
      influences uterine function.

PMID- 30192029
TI  - Association of methacholine challenge test with diagnosis of chronic lung
      allograft dysfunction in lung transplant patients.
AB  - BACKGROUND: Chronic lung allograft dysfunction (CLAD) is a complication of lung
      transplantation. We sought to determine whether bronchial hyperresponsiveness
      detected by the methacholine challenge test (MCT) at 3 months after lung
      transplant (LT) predicts the development of CLAD. METHODS: We performed a
      retrospective cohort study of 140 LT patients between 1/2008 and 6/2014 who
      underwent MCT at 3 months after LT. Pearson's chi-squared test and Kruskal-Wallis
      test were used to compare categorical and continuous variables, respectively. Cox
      proportional hazards modeling was used to evaluate the association between CLAD
      and MCT. RESULTS: Methacholine challenge test+ was associated with the
      development of overall CLAD (adjusted hazards ratio [aHR]: 3.47; 95% confidence
      interval [95% CI]: 1.71, 7.03; P = 0.001) and CLAD within 3 years (aHR: 4.98;
      95%CI: 1.84, 13.48; P = 0.002). Subgroup analysis showed that MCT (+) is
      associated with overall CLAD in single lung transplant (SLT) (aHR: 8.18; 95% CI:
      2.22, 30.09; P = 0.002), double lung transplant (DLT) (aHR: 3.27; 95% CI: 1.22,
      8.78; P = 0.02) and CLAD within 3 years in DLT patients (aHR: 6.76; 95% CI: 1.71,
      26.74; P = 0.01). CONCLUSION: Methacholine challenge test+ at 3 months after LT
      is associated with the development of overall CLAD. Positive MCT could predict
      the development of early CLAD within 3 years in DLT patients.

PMID- 30192030
TI  - GNE myopathy in the bedouin population of Kuwait: Genetics, prevalence, and
      clinical description.
AB  - INTRODUCTION: GNE myopathy is a rare recessive myopathy caused by mutations in
      the GNE gene. It is mainly a distal myopathy with relative sparing of the
      quadriceps muscle. METHODS: Patients with distal myopathies from Kuwait were
      examined and tested for the Middle Eastern GNE gene founder mutation, p.M743T.
      Patients were further studied for disease-associated features. RESULTS: GNE
      myopathy was confirmed in 14 of the 37 patients (37.8%) screened. All cases were
      caused by the p.M743T mutation. Age of onset and time from disease onset to loss
      of ambulation were variable. Both wasted and hypertrophied calf muscles were
      noted. Severely affected quadriceps were present in 1 patient, and ptosis,
      ophthalmoplegia, and tongue wasting in another. DISCUSSION: The scope of the
      p.M743T mutation now includes the Arabian Peninsula. Variations in age of onset,
      disease progression, and distribution in patients harboring the same mutation
      suggest the role of other genetic- and environment-modifying factors. Muscle
      Nerve 58: 700-707, 2018.

PMID- 30192031
TI  - Blood lysosphingolipids accumulation in patients with parkinson's disease with
      glucocerebrosidase 1 mutations.
AB  - INTRODUCTION: Glucocerebrosidase 1 mutations, the most common genetic contributor
      to Parkinson's disease (PD), have been associated with decreased
      glucocerebrosidase enzymatic activity in PD patients with glucocerebrosidase 1
      mutations (glucocerebrosidase 1-PD). However, it is unknown whether this decrease
      in enzymatic activity leads to lysosphingolipid accumulations. METHODS: The
      levels of hexosylsphingosines, globotriaosylsphingosine, sphingomyelin, and
      sphingomyelin-509 were measured in dried blood spots from glucocerebrosidase 1-PD
      patients (n = 23), sporadic PD patients (n = 105), Gaucher disease patients (n =
      32), and controls (n = 88) by liquid chromatography-tandem mass spectrometry.
      RESULTS: Glucocerebrosidase 1-PD patients had increased hexosylsphingosine levels
      when compared with sporadic PD patients (P < .001) and controls (P < .0001).
      Hexosylsphingosine levels were increased in glucocerebrosidase 1 mutation
      carriers of glucocerebrosidase 1 (L444P; N370S; n = 11, P = .001) and
      glucocerebrosidase 1 polymorphic variants (E326K, T369M) associated with PD (n =
      12, P = .04) when compared with controls. CONCLUSIONS: Lysosphingolipid
      accumulations in PD patients who bear glucocerebrosidase 1 mutations suggest that
      substrate reduction therapy might be viewed as a possible strategy for
      glucocerebrosidase 1-PD treatment. (c) 2018 International Parkinson and Movement
      Disorder Society.

PMID- 30192032
TI  - Reply to "The paper that wrote itself-a ghost story".

PMID- 30192033
TI  - Arrhythmia induction using isoproterenol or epinephrine during electrophysiology
      study for supraventricular tachycardia.
AB  - BACKGROUND: Electrophysiology study (EPS) is an important part of the diagnosis
      and workup for supraventricular tachycardia (SVT). Provocative medications are
      used to induce arrhythmias, when they are not inducible at baseline. The most
      common medication is the beta1-specific agonist, isoproterenol, but recent price
      increases have resulted in a shift toward the nonspecific agonist, epinephrine.
      OBJECTIVE: We hypothesize that isoproterenol is a better induction agent for SVT
      during EPS than epinephrine. METHODS: We created a retrospective cohort of 131
      patients, who underwent EPS and required medication infusion with either
      isoproterenol or epinephrine for SVT induction. The primary outcome was
      arrhythmia induction. RESULTS: Successful induction was achieved in 71% of
      isoproterenol cases and 53% of epinephrine cases (P = 0.020). Isoproterenol was
      significantly better than epinephrine for SVT induction during EPS (odds ratio
      [OR], 2.35; 95% confidence interval [CI], 1.14-4.85; P = 0.021). There was no
      difference in baseline variables or complications between the two groups. Other
      variables associated with successful arrhythmia induction included a longer
      procedure duration and atrioventricular nodal re-entry tachycardia as the
      clinical arrhythmia. In a multivariable model, isoproterenol remained
      significantly associated with successful induction (OR, 2.57; 95% CI, 1.002-6.59;
      P = 0.05). CONCLUSIONS: Isoproterenol was significantly better than epinephrine
      for SVT arrhythmia induction. However, epinephrine was safe and successfully
      induced arrhythmias in the majority of patients who received it. Furthermore,
      when atropine was added in epinephrine-refractory cases, in a post hoc analysis
      there was no difference in arrhythmia induction between medications. Cost savings
      could thus be significant without compromising safety.

PMID- 30192034
TI  - Acral pseudolymphomatous angiokeratoma of children (APACHE): Dermoscopic features
      and successful treatment with CO2 laser.

PMID- 30192035
TI  - Light-Induced Spin Transitions in Copper-Nitroxide-Based Switchable Molecular
      Magnets: Insights from Periodic DFT+U Calculations.
AB  - The electronic structure and magnetic interactions of three members of the
      breathing crystal Cu(hfac)2 LR family (hfac=hexafluoroacetylacetonato, LR
      =pyrazole-substituted nitronyl nitroxides with R=Me, Et, Pr, iPr, Bu ), mainly
      Cu(hfac)2 LPr (1), Cu(hfac)2 LBu ?0.5 C8 H18 (2) and Cu(hfac)2 LBu ?0.5 C8 H10
      (3), have been analyzed by means of periodic plane-wave based DFT+U calculations.
      These CuII -nitroxide based molecular magnets display thermally and optically
      induced switchable behavior and light-induced excited spin state trapping
      phenomena. The calculations confirm the presence of temperature-dependent
      exchange interaction within the spin triads formed by the nitroxide-copper(II)
      nitroxide units, in line with the changes observed in the effective magnetic
      moment. Moreover, they quantify the interchain interaction mediated by the
      terminal nitroxide group of two spin triads in neighboring polymer chains. This
      interaction competes with the exchange interaction within the spin triads at high
      temperature, and introduces 1D exchange channels that do not coincide with the
      polymeric chains. The density of states reveal that the low-lying conduction
      states potentially involved in the UV/Vis transitions are located on the
      nitroxide radicals, the hfac groups and the Cu atoms. Then, the density of states
      is almost independent of the solvent and the R group. This suggests the
      possibility of light-induced spin switching for other members of this family. The
      500 nm band of the low-temperature phase can be ascribed to a ligand-to-metal
      charge transfer transition between the nitroxide and Cu bands.

PMID- 30192036
TI  - Gait pattern changes after six-minute walk test in persons with multiple
      sclerosis.
AB  - OBJECTIVE: To examine the effect of induced fatigue on spatiotemporal gait
      parameters in persons with multiple sclerosis (PwMS) by using 6-min walk test
      (6MWT). METHODS: A cross-sectional study with a control group (25 healthy
      persons) was performed. Fifty-six PwMS (37 female) were divided into three groups
      according to their level of disability, as measured by the expanded disability
      status scale (EDSS): mild (n = 23, EDSS = 1.0-3.5), moderate (n = 19, EDSS = 4.0
      5.5), and severe (n = 12, EDSS = 6.0-6.5). Spatiotemporal gait parameters were
      measured by the GAITRite electronic walkway before and after 6MWT performance. In
      addition, to determine the level of fatigue in PwMS, the participants completed
      the questionnaire modified fatigue impact scale (MFIS) before performing the
      6MWT. Statistical analyses were performed to compare intragroup and intergroup
      differences. RESULTS: Fatigue level was lower in the mild (37.6 +/- 20.5) versus
      moderate (54.3 +/- 17.2) versus severe (53.6 +/- 12.9) groups (p < 0.05).
      Significant differences were found among all the groups in terms of the distance
      walked during the 6MWT (p = 0.001) and of the spatiotemporal gait parameters:
      gait velocity (cm/s), cadence (steps/min), and step length (cm) decreased and, on
      the contrary, step time (sec), stance, and double support time (% gait cycle)
      increased when EDSS scores were higher (p < 0.05). The percentage of change (%)
      in the spatiotemporal gait parameters, after 6MWT performance, was statistically
      significant in the moderate and severe groups: gait velocity (-8.8%, -25.9%) and
      step length (-6.5%, -13.4%) decreased, whereas step time (3.0%, 15.0%), double
      support time (8.8%, 19.1%), step time asymmetry (32.1%, 64.0%), and single
      support asymmetry (60.0%, 74.7%) increased (p < 0.05). CONCLUSIONS: Gait pattern
      worsen after performing a walking-induced fatigue test, such as 6MWT, in moderate
      severe PwMS (EDSS >= 4.0). Identifying these gait alterations will allow
      physiotherapists to determine specific therapeutic objectives.

PMID- 30192037
TI  - A novel method to measure steroid hormone concentrations in walrus bone from
      archaeological, historical, and modern time periods using liquid
      chromatography/tandem mass spectrometry.
AB  - RATIONALE: A liquid chromatography/tandem mass spectrometry (LC/MS/MS) method was
      validated and utilized to measure and analyze four steroid hormones related to
      stress and reproduction in individual samples from a novel tissue, Pacific walrus
      (Odobenus rosmarus divergens, herein walrus) bone. This method determines steroid
      hormone concentrations in the remote walrus population over millennia from
      archaeological (>200 bp), historical (200-20 bp), and modern (2014-2016) time
      periods. METHODS: Lipids were extracted from walrus bone collected from these
      periods using methanol before LC/MS/MS analysis. Isotopically labeled internal
      standards for each target hormone were added to every sample. Analytical and
      physiological validations were performed. Additionally, a tissue comparison was
      done among paired walrus bone, serum, and blubber samples. A rapid resolution
      liquid chromatography system coupled to a QqQ mass spectrometer was used to
      analyze all samples after derivatization for progesterone, testosterone,
      cortisol, and estradiol concentrations. Multiple reaction monitoring was used for
      MS analysis and data were acquired in positive electrospray ionization mode.
      RESULTS: Progesterone, testosterone, cortisol, and estradiol were linear along
      their respective standard calibration curves based on their R2 values (all >
      0.99). Accuracy ranged from 93-111% for all hormones. The recovery of extraction,
      recovery of hormones without matrix effect, was 92-101%. The overall process
      efficiency of our method for measuring hormones in walrus bone was 93-112%.
      Progesterone and testosterone concentrations were not affected by reproductive
      status among adult females and males, respectively. However, estradiol was
      different among pregnant and non-pregnant adult females. Overall, steroid
      hormones reflect a long-term reservoir in cortical bone. This method was also
      successfully applied to walrus bone as old as 3585 bp. CONCLUSIONS: LC/MS/MS
      analysis of bone tissue (0.2-0.3 g) provides stress and reproductive data from
      elusive walruses that were alive thousands of years ago. Based on physiological
      validations, tissue comparison, and published literature, steroid hormone
      concentrations measured in walrus cortical bone could represent an accumulated
      average around a 10-20-year time span. By investigating how stress and
      reproductive physiology may have changed over the past ~3000 years based on bone
      steroid hormone concentrations, this method will help answer how physiologically
      resilient walruses are to climate change in the Arctic.

PMID- 30192038
TI  - Vascular conspicuity differs among injection protocols and scanner types for
      canine multiphasic abdominal computed tomographic angiography.
AB  - Multiphasic multidetector computed tomographic angiography is a standard
      diagnostic test for canine abdominal vascular disorders. Three imaging protocols
      have been previously described. The test-bolus protocol allows precise timing but
      can be time consuming to perform. Bolus-tracking software is fast and easy to use
      but can be problematic for exact timing of vascular phases. A recently described
      fixed-injection-duration protocol is not influenced by body weight and provides a
      wider temporal window for arterial acquisitions. Objectives of this retrospective
      and prospective, multicentric, method comparison study were to determine which of
      the three multidetector computed tomographic angiography protocols allows best
      vascular conspicuity of the canine abdomen and to assess the influence of
      different multidetector computed tomography (CT) scanners on study quality.
      Triple-phase multidetector computed tomographic angiography canine abdominal
      studies from 30 dogs were retrospectively retrieved from three different
      institutions. Each institution performed one of the three computed tomographic
      angiography protocols (4-row and 16-row multidetector CT). Prospectively, the
      three protocols were also acquired with similar conditions on a 64-row MDCT in 21
      dogs. Main abdominal vessels were scored by blinded readers for each phase. The
      fixed-injection-duration protocol had the best combined arterial and portal
      vascular conspicuity on scanners of limited speed, while the test-bolus protocol
      provided the best overall vascular conspicuity on 64-row multidetector CT
      scanner. The quality of arterial studies performed on 64-row MDCT scanner was
      improved compared to the ones performed on four- to 16-row multidetector CT
      scanners. Findings supported the fixed-injection-duration protocol as the best
      compromise between an ideal portal vascular enhancement and an easily
      reproducible protocol on scanners with low and high number of detector rows.

PMID- 30192039
TI  - Body mass index, peer victimization, and body dissatisfaction across 7 years of
      childhood and adolescence: Evidence of moderated and mediated pathways.
AB  - Numerous studies have reported that children and adolescents who are overweight
      are more likely to get bullied, yet the literature is replete with methodological
      limitations. We examined the transactional associations between peer
      victimization and body mass index (BMI), considering potential mediating (body
      dissatisfaction) and moderating (biological sex) factors. Participants (n = 631)
      came from the McMaster Teen Study, where students were assessed annually between
      Grades 5-11, approximately half were girls (53.9%), and the majority were white
      (76.4%). Peer victimization (from Grade 5) and body dissatisfaction (from Grade
      6) were self-reported by students, while parents reported their child's height
      and weight (from Grade 5). Cascade models were built up sequentially using path
      analysis across 2-year increments (Grades 5, 7, 9, and 11). The final model had
      excellent fit to the data (chi2  = 73.961, df = 66, p = 0.234). Grade 5 peer
      victimization had a direct effect on BMI across a 2-year period in girls (b =
      0.59, SE = 0.21, p = 0.005) and boys (b = 0.82, SE = 0.30, p = 0.006), and an
      indirect effect on BMI via body dissatisfaction across a 4-year period (b =
      0.074, 95% CI = 0.012-0.152, p = 0.036). At no point did BMI directly increase
      risk for peer victimization, yet there were indirect effects via body
      dissatisfaction among girls but not boys. Peer victimization and body
      dissatisfaction were proximally and longitudinally related at every time point
      and there was a transactional association in late-adolescence among girls but not
      boys. Targeting modifiable factors in the social (peer victimization) and
      psychological (body dissatisfaction) domains may limit accelerated weight gain
      and the health risks associated with excess adiposity.

PMID- 30192041
TI  - Adherence trajectories of buprenorphine therapy among pregnant women in a large
      state Medicaid program in the United States.
AB  - PURPOSE: Little is known about the longitudinal patterns of buprenorphine
      adherence among pregnant women with opioid use disorder, especially when late
      initiation, nonadherence, or early discontinuation of buprenorphine during
      pregnancy may increase the risk of adverse outcomes. We aimed to identify
      distinct trajectories of buprenorphine use during pregnancy, and factors
      associated with these trajectories in Medicaid-enrolled pregnant women. METHODS:
      A retrospective cohort study included 2361 Pennsylvania Medicaid enrollees aged
      15 to 46 having buprenorphine therapy during pregnancy and a live birth between
      2008 and 2015. We used group-based trajectory models to identify buprenorphine
      use patterns in the 40 weeks prior to delivery and 12 weeks postdelivery.
      Multivariable multinomial logistic regression models were used to identify
      factors associated with specific trajectories. RESULTS: Six distinct trajectories
      were identified. Four groups initiated buprenorphine during the first trimester
      of the pregnancy (early initiators): 31.6% with persistently high adherence,
      15.1% with moderate-to-high adherence, 10.5% with declining adherence, and 16.7%
      with early discontinuation. Two groups did not initiate buprenorphine until
      midsecond or third trimester (late initiators): 13.5% had moderate-to-high
      adherence and 12.6% had low-to-moderate adherence. Factors significantly
      associated with late initiation and discontinuation were younger age, non-white
      race, residents of rural counties, fewer outpatient visits, more frequent
      emergency department visits and hospitalizations, and lower buprenorphine daily
      dose. CONCLUSIONS: Six buprenorphine treatment trajectories during pregnancy were
      identified in this population-based Medicaid cohort, with 25% of women initiating
      buprenorphine late during pregnancy. Understanding trajectories of buprenorphine
      use and factors associated with discontinuation/nonadherence may guide
      integration of behavioral treatment with obstetrical/gynecological care to
      improve buprenorphine treatment during pregnancy.

PMID- 30192040
TI  - Impact of electrical connections between ipsilateral pulmonary veins on the
      second-generation cryoballoon ablation procedure.
AB  - BACKGROUND: Electrical connections between ipsilateral pulmonary veins (PVs) have
      been reported histologically and electrophysiologically. This study investigated
      the impact of electrical connections between ipsilateral PVs on PV isolation
      using second-generation cryoballoons (CB2-PVI). METHODS: Five hundred eleven
      atrial fibrillation patients, without any PV anomalies, underwent CB2-PVI using
      one 28-mm balloon and a single 3-minute freeze strategy without any bonus
      applications. RESULTS: Overall, 1966 of 2044 (96.2%) PVs were isolated
      exclusively by using 28-mm cryoballoons. Among them, 13 left superior PV (LSPVs)
      and two right superior PV were not persistently isolated by the first application
      despite a complete vein occlusion, but were isolated by subsequent applications
      targeting other ipsilateral PVs. Among the 13 LSPVs, six were transiently
      isolated by 87 (62-146) second time-to-isolation LSPV applications, but were
      immediately reconnected after the application. The nadir balloon temperature
      during the LSPV application was similar between the 13 LSPVs not isolated by the
      LSPV application but were not so by subsequent left inferior PV (LIPV)
      applications and the 488 LSPVs persistently isolated by LSPV applications (-49.4C
      +/- 4.3C vs -50.8C +/- 5.1C; P = 0.328). In 59 patients in whom the initial LSPV
      application failed despite a complete occlusion, LIPVs were targeted for the
      second applications in 31 patients, and both the LSPV and LIPV were
      simultaneously isolated in 13 of 31 (41.9%). CONCLUSIONS: Electrical connections
      between ipsilateral PVs could have an impact on the CB2-PVI procedure. When the
      vein isolation failed despite a complete occlusion, especially for left
      ipsilateral PVs, it was reasonable to target the other ipsilateral PV instead of
      repeatedly targeting the same vein.

PMID- 30192042
TI  - Recommendations for interpreting the loss of function PVS1 ACMG/AMP variant
      criterion.
AB  - The 2015 ACMG/AMP sequence variant interpretation guideline provided a framework
      for classifying variants based on several benign and pathogenic evidence
      criteria, including a pathogenic criterion (PVS1) for predicted loss of function
      variants. However, the guideline did not elaborate on specific considerations for
      the different types of loss of function variants, nor did it provide decision
      making pathways assimilating information about variant type, its location, or any
      additional evidence for the likelihood of a true null effect. Furthermore, this
      guideline did not take into account the relative strengths for each evidence type
      and the final outcome of their combinations with respect to PVS1 strength.
      Finally, criteria specifying the genes for which PVS1 can be applied are still
      missing. Here, as part of the ClinGen Sequence Variant Interpretation (SVI)
      Workgroup's goal of refining ACMG/AMP criteria, we provide recommendations for
      applying the PVS1 criterion using detailed guidance addressing the above
      mentioned gaps. Evaluation of the refined criterion by seven disease-specific
      groups using heterogeneous types of loss of function variants (n = 56) showed 89%
      agreement with the new recommendation, while discrepancies in six variants (11%)
      were appropriately due to disease-specific refinements. Our recommendations will
      facilitate consistent and accurate interpretation of predicted loss of function
      variants.

PMID- 30192043
TI  - Modular Enzymatic Cascade Synthesis of Vitamin B5 and Its Derivatives.
AB  - Access to vitamin B5 [(R)-pantothenic acid] and both diastereoisomers of alpha
      methyl-substituted vitamin B5 [(R)- and (S)-3-((R)-2,4-dihydroxy-3,3
      dimethylbutanamido)-2-methylpropanoic acid] was achieved using a modular three
      step biocatalytic cascade involving 3-methylaspartate ammonia lyase (MAL),
      aspartate-alpha-decarboxylase (ADC), beta-methylaspartate-alpha-decarboxylase
      (CrpG) or glutamate decarboxylase (GAD), and pantothenate synthetase (PS)
      enzymes. Starting from simple non-chiral dicarboxylic acids (either fumaric acid
      or mesaconic acid), vitamin B5 and both diastereoisomers of alpha-methyl
      substituted vitamin B5 , which are valuable precursors for promising
      antimicrobials against Plasmodium falciparum and multidrug-resistant
      Staphylococcus aureus, can be generated in good yields (up to 70 %) and excellent
      enantiopurity (>99 % ee). This newly developed cascade process may be tailored
      and used for the biocatalytic production of various vitamin B5 derivatives by
      modifying the pantoyl or beta-alanine moiety.

PMID- 30192044
TI  - Course of major depressive disorder after pregnancy and the postpartum period.
AB  - BACKGROUND: Maternal major depressive disorder (MDD) has an adverse effect on
      child development and increases risk for child psychopathology. It is paramount
      to understand the course of maternal depression during the childhood years
      particularly before, during, and after pregnancy. OBJECTIVE: To follow the course
      of MDD in women with prior histories of depression followed during an index
      pregnancy. METHODS: Subjects were women with histories of MDD who had
      participated in prior prospective, observational studies during pregnancy. In the
      follow-up, participants completed a structured interview that addressed (1) the
      course of MDD since their index pregnancy, (2) new psychiatric diagnoses, and (3)
      the course of MDD and treatment across subsequent pregnancies. RESULTS: Out of
      129 eligible women, 48.8% participated (N = 63) with an average/mean time of 12.9
      years (SD = 1.9, 8.8-16.7) elapsed since participation in the prior pregnancy
      studies. Although approximately one third reported sustained remission from MDD
      since the pregnancy during which they had been originally followed, of the
      remaining two thirds of women who reported subsequent depressive episodes, almost
      one fifth (~12% of the total sample) endorsed depression more than 50% of the
      time following their index pregnancy. A total of 6.3% of the women with previous
      validated diagnoses of MDD reported new diagnoses of bipolar disorder. Women
      reported similar treatment choices regarding the use of antidepressants during
      pregnancies subsequent to the one followed in the previous study. CONCLUSION:
      Women with MDD experienced high rates of recurrent depression across the
      childbearing years. This represents a critical variable for clinical care and
      research.

PMID- 30192045
TI  - Effects of clothianidin-treated seed on the arthropod community in a mid-Atlantic
      no-till corn agroecosystem.
AB  - BACKGROUND: Nearly all corn seed in the US is coated with neonicotinoid
      insecticides to protect against soil and foliar arthropod pests. Exposure in the
      soil and the systemic activity in the plant can pose non-target risks. We
      assessed the community-level effects of clothianidin-treated seed on the
      diversity and abundance of arthropod communities in a no-till corn agroecosystem
      over a single growing season. RESULTS: Epigeal and foliage-dwelling communities
      were disturbed by the clothianidin seed treatment, with significant negative and
      positive changes in taxa abundances. Clothianidin reduced the abundance of minute
      pirate bugs by 66.2%, lady beetles by 44.7%, ants by 43.4%, ground beetle adults
      and larvae by 31.7%, and rove beetles by 44.1% during the early corn growth
      stages. Herbivores, particularly thrips, were more negatively affected by
      clothianidin than other trophic groups. In contrast, some groups, such as
      collembolans and leafhoppers, exhibited significantly higher abundances in the
      seed treated plots. CONCLUSION: Clothianidin primarily influenced arthropod
      communities during the 4 weeks following planting, with disruptions to major
      natural enemy taxa, but communities showed trends toward recovery at the later
      corn stages. While the insecticide suppressed multiple herbivores, none were
      economically damaging to corn; thus, the pest suppression benefits of
      clothianidin observed in this study did not justify the non-target impacts. (c)
      2018 Society of Chemical Industry.

PMID- 30192046
TI  - Evolution of the biocontrol active substances in the framework of the European
      Pesticide Regulation (EC) No. 1107/2009.
AB  - BACKGROUND: The use of biocontrol agents (BCA) is growing strongly with a market
      of ?1.9 billion worldwide and ?542 million in Europe, and an estimated annual
      growth of between 15% and 20%. Biocontrol substances use natural mechanisms as
      part of integrated pest management. With the exception of macro-organisms,
      substances or products comprising microorganisms, semiochemicals and natural
      substances depend on plant protection Regulation (EC) No. 1107/2009. RESULTS:
      When this regulation came into force, a number of BCA had already been approved.
      The total number of BCA rose during the period 2011-2018 to ~ 60 substances in
      line with global growth in approved substances. This growth was not smooth or
      equal between biocontrol categories; the microorganisms category increased the
      most, with a doubling of the number of approved substances in use, followed by
      natural substances and semiochemicals. CONCLUSION: This positive development has
      been influenced by many factors such as scientific advances and environmental
      characteristics. However, some obstacles remain that limit the development of BCA
      (market size, variability in effectiveness, etc.). Regulatory measures could be a
      key to enhancing the development of biocontrol registrations. (c) 2018 Society of
      Chemical Industry.

PMID- 30192048
TI  - Teaching human factors: a near-peer approach.
AB  - BACKGROUND: An understanding of human factors and ergonomics (HFE) is critical
      for optimal team performance, and is an important component of the postgraduate
      medical curriculum. This training is often delivered by senior clinicians with
      experience of using and teaching HFE concepts. A lack of availability of these
      experienced tutors can be a constraint on training provision. CONTEXT: A near
      peer tutor (NPT) approach was used to deliver a classroom-based HFE course to
      postgraduate doctors, supported by a tutor handbook. We aimed to compare feedback
      from this course with a previous course taught by experienced tutors. METHODS:
      Learners (n = 21) attending this course were divided into small groups, with one
      NPT per group. Each group viewed three video reconstructions of incidents from
      health care and other industries, followed by a structured discussion. Learners
      were encouraged to recognise concepts from HFE, and to develop changes to their
      own practice. The NPTs were guided through the session by a tutor handbook, which
      they received in advance. Human factors and ergonomics training is associated
      with a significant decrease in error RESULTS: Initial and 2-month feedback was
      extremely positive, with Likert scores of 5/5 for Organisation, Content, Teaching
      Methods and Overall Impression. This was significantly (p < 0.05) better than
      feedback from a previous HFE course with senior tutors. Median NPT confidence
      ratings before and after receiving the handbook were 4/10 and 8/10, respectively.
      CONCLUSIONS: These results support the use of NPTs in delivering HFE training to
      postgraduate doctors. Self-reported confidence is increased by providing a
      handbook with discussion prompts. Training in HFE does not require senior tutors
      with significant clinical commitments, and can be provided to a high standard by
      NPTs.

PMID- 30192047
TI  - Phytoene and Phytofluene Isolated from a Tomato Extract are Readily Incorporated
      in Mixed Micelles and Absorbed by Caco-2 Cells, as Compared to Lycopene, and SR
      BI is Involved in their Cellular Uptake.
AB  - SCOPE: Absorption mechanisms of phytoene (PT) and phytofluene (PTF) are poorly
      known. The main objectives of the study are to measure their micellization and
      intestinal cell uptake efficiencies and to compare them to those of commonly
      consumed carotenoids. Other objectives are to assess the involvement of
      protein(s) in their cellular uptake and whether they compete with other
      carotenoids for micellization and cellular uptake. METHODS AND RESULTS: Tomato
      extract-purified PT and PTF, mainly present as cis-isomers, are much better
      incorporated in synthetic mixed micelles than pure all-trans lycopene. PT impairs
      lycopene micellization (-56%, P < 0.05) while PT and PTF do not significantly
      affect the micellization of other carotenoids, and vice versa. At low
      concentration, Caco-2 PTF uptake is higher (P < 0.05) than that of PT and
      lycopene (29%, 21%, and not detectable). SR-BI, but not CD36 neither NPC1L1, is
      involved in PT and PTF uptake. PT and PTF impair (p < 0.05) beta-carotene uptake
      (-13 and -22%, respectively). CONCLUSIONS: The high bioaccessibility of PT and
      PTF can be partly explained by their high micellization efficiency, which is
      likely due to their natural cis isomerization and/or to their high molecular
      flexibility. SR-BI is involved in their cellular uptake, which can explain
      competitions with other carotenoids.

PMID- 30192049
TI  - Examination of the Deubiquitylation Site Selectivity of USP51 by Using Chemically
      Synthesized Ubiquitylated Histones.
AB  - Histone ubiquitylation and deubiquitylation processes and the mechanisms of their
      regulation are closely relevant to the field of epigenetics. Recently, the
      deubiquitylating enzyme USP51 was reported to selectively cleave ubiquitylation
      on histone H2A at K13 or K15 (i.e., H2AK13Ub and H2AK15Ub), but not at K119
      (i.e., H2AK119Ub), in nucleosomes in vivo. To elucidate the mechanism for the
      selectivity of USP51, we constructed structurally well-defined in vitro protein
      systems with a ubiquitin modification at precise sites. A total chemical protein
      synthesis procedure was developed, wherein hydrazide-based native chemical
      ligation was used to efficiently generate five ubiquitylated histones (H2AK13Ub,
      H2AK15Ub, H2AK119Ub, H2BK34Ub, and H2BK120Ub). These synthetic ubiquitylated
      histones were assembled into nucleosomes and subjected to in vitro USP51
      deubiquitylation assays. Surprisingly, USP51 did not show preference between
      H2AK13/15Ub and H2AK119Ub, in contrast to previous in vivo observations.
      Accordingly, an understanding of the selectivity of USP51 may require
      consideration of other factors, such as alternative pre-existing histone
      modifications, competitive reader proteins, or different nucleosome quality among
      the in vivo extraction nucleosome and the in vitro reconstitution one. Further
      experiments established that USP51 in vitro could deubiquitylate a nucleosome
      carrying H2BK120Ub, but not H2BK34Ub. Molecular dynamics simulations suggested
      that USP51-catalyzed hydrolysis of ubiquitylated nucleosomes was affected by
      steric hindrance of the isopeptide bond.

PMID- 30192050
TI  - Novel film-forming formulations of the biocontrol agent Candida sake CPA-1:
      biocontrol efficacy and performance at field conditions in organic wine grapes.
AB  - BACKGROUND: The biocontrol agent (BCA) Candida sake CPA-1 has previously
      effectively reduced Botrytis bunch rot (BBR) and it was also suggested as a
      promising strategy to control sour rot in grapes under field conditions. However,
      biocontrol efficacy of solid formulations of CPA-1 has never been tested in field
      trials. The present study aims to confirm the efficacy against BBR and sour rot
      in grapes under field conditions of two novel formulations recently developed by
      the addition of biodegradable coatings using a fluidized-bed spray-drying system.
      RESULTS: Novel film-forming formulations of the BCA C. sake CPA-1 controlled B.
      cinerea as well as liquid formulation. Sour rot control resulted better in the
      second season and severity reductions were more satisfactory than incidence
      control. Visual and cryoSEM observations revealed that film-forming treatments
      were uniformly distributed on plant surfaces. CPA-1 coating could be observed on
      grapes at harvest time. CONCLUSION: The results of this work suggest that solid
      formulations would be a competitive alternative to conventional fungicides
      because they were easy to package and transport, and cell viability could be
      maintained for a long period of time. (c) 2018 Society of Chemical Industry.

PMID- 30192052
TI  - Gastric obstruction secondary to a band adhesion post-Nissen fundoplication: a
      rare entity.

PMID- 30192051
TI  - A salicylic acid derivative extends the lifespan of Caenorhabditis elegans by
      activating autophagy and the mitochondrial unfolded protein response.
AB  - Plant extracts containing salicylates are probably the most ancient remedies to
      reduce fever and ease aches of all kind. Recently, it has been shown that
      salicylates activate adenosine monophosphate-activated kinase (AMPK), which is
      now considered as a promising target to slow down aging and prevent age-related
      diseases in humans. Beneficial effects of AMPK activation on lifespan have been
      discovered in the model organism Caenorhabditis elegans (C. elegans). Indeed,
      salicylic acid and acetylsalicylic acid extend lifespan in worms by activating
      AMPK and the forkhead transcription factor DAF-16/FOXO. Here, we investigated
      whether another salicylic acid derivative 5-octanoyl salicylic acid (C8-SA),
      developed as a controlled skin exfoliating ingredient, had similar properties
      using C. elegans as a model. We show that C8-SA increases lifespan of C. elegans
      and that a variety of pathways and genes are required for C8-SA-mediated lifespan
      extension. C8-SA activates AMPK and inhibits TOR both in nematodes and in primary
      human keratinocytes. We also show that C8-SA can induce both autophagy and the
      mitochondrial unfolded protein response (UPRmit ) in nematodes. This induction of
      both processes is fully required for lifespan extension in the worm. In addition,
      we found that the activation of autophagy by C8-SA fails to occur in worms with
      compromised UPRmit , suggesting a mechanistic link between these two processes.
      Mutants that are defective in the mitochondrial unfolded protein response exhibit
      constitutive high autophagy levels. Taken together, these data therefore suggest
      that C8-SA positively impacts longevity in worms through induction of autophagy
      and the UPRmit .

PMID- 30192054
TI  - The pursuit of excellence.

PMID- 30192053
TI  - Cell death triggered by the P25 protein in Potato virus X-associated synergisms
      results from endoplasmic reticulum stress in Nicotiana benthamiana.
AB  - The synergistic interaction of Potato virus X (PVX) with a number of potyviruses
      results in systemic necrosis in Nicotiana spp. Previous investigations have
      indicated that the viral suppressor of RNA silencing (VSR) protein P25 of PVX
      triggers systemic necrosis in PVX-associated synergisms in a threshold-dependent
      manner. However, little is still known about the cellular processes that lead to
      this necrosis, and whether the VSR activity of P25 is involved in its
      elicitation. Here, we show that transient expression of P25 in the presence of
      VSRs from different viruses, including the helper component-proteinase (HC-Pro)
      of potyviruses, induces endoplasmic reticulum (ER) stress and the unfolded
      protein response (UPR), which ultimately lead to ER collapse. However, the host
      RNA silencing pathway was dispensable for the elicitation of cell death by P25.
      Confocal microscopy studies in leaf patches co-expressing P25 and HC-Pro showed
      dramatic alterations in ER membrane structures, which correlated with the up
      regulation of bZIP60 and several ER-resident chaperones, including the ER luminal
      binding protein (BiP). Overexpression of BiP alleviated the cell death induced by
      the potexviral P25 protein when expressed together with VSRs derived from
      different viruses. Conversely, silencing of the UPR master regulator, bZIP60, led
      to an increase in cell death elicited by the P25/HC-Pro combination as well as by
      PVX-associated synergism. In addition to its role as a negative regulator of P25
      induced cell death, UPR partially restricted PVX infection. Thus, systemic
      necrosis caused by PVX-associated synergistic infections is probably the effect
      of an unmitigated ER stress following the overaccumulation of a viral protein,
      P25, with ER remodelling activity.

PMID- 30192055
TI  - Bioinspired Multi-Activities 4D Printing Objects: A New Approach Toward Complex
      Tissue Engineering.
AB  - 4D printing is an innovative approach which might in a near future lead to the
      achievement of highly complex smart materials. The authors describe a new
      strategy for the achievement of 4D printed objects with multiple biological
      activities. These activities are generated through the entrapment, during 3D
      printing, of two distinct enzymes (alkaline phosphatase and thrombin). These two
      enzymes give then the ability to the 4D printed object to generate bioactivities
      useful for in vitro tissue engineering. Indeed, it is shown that the entrapped
      alkaline phosphatase enables the localized and pre-programmed calcification of
      some 3D object parts while the diffusion of thrombin from the object permits the
      formation of fibrin biofilm (including living cells) directly at the surface of
      3D object. Both activities and enzyme behavior within the 4D printed hydrogel are
      characterized through enzymatic measurements, microscopy, magnetic resonance
      imaging (MRI), and cell seeding.

PMID- 30192056
TI  - Utility of magnetic resonance imaging in differentiating renal infection from
      tumour: a not uncommon clinical conundrum.

PMID- 30192057
TI  - Teaching in longitudinal integrated clerkships: the seven 'C's.

PMID- 30192058
TI  - Incomplete reproductive isolation between Rhododendron taxa enables hybrid
      formation and persistence.
AB  - The evolutionary consequences of hybridization ultimately depend on the magnitude
      of reproductive isolation between hybrids and their parents. We evaluated the
      relative contributions of pre- and post-zygotic barriers to reproduction for
      hybrid formation, hybrid persistence and potential for reproductive isolation of
      hybrids formed between two Rhododendron species, R. spiciferum and R.
      spinuliferum. Our study established that incomplete reproductive isolation
      promotes hybrid formation and persistence and delays hybrid speciation. All pre
      zygotic barriers to reproduction leading to hybrid formation are incomplete:
      parental species have overlapping flowering; they share the same pollinators;
      reciprocal assessments of pollen tube germination and growth do not differ among
      parents. The absence of post-zygotic barriers between parental taxa indicates
      that the persistence of hybrids is likely. Reproductive isolation was incomplete
      between hybrids and parents in all cases studied, although asymmetric differences
      in reproductive fitness were prevalent and possibly explain the genetic structure
      of natural hybrid swarms where hybridization is known to be bidirectional but
      asymmetric. Introgression, rather than speciation, is a probable evolutionary
      outcome of hybridization between the two Rhododendron taxa. Our study provides
      insights into understanding the evolutionary implications of natural
      hybridization in woody plants.

PMID- 30192059
TI  - Hidden Dicarbene Nature of Acetylenes and Captodative Bonding on Carbon.
AB  - DFT derived molecular electrostatic potential (MESP), 13C NMR chemical shift
      (delta), bond order and coordination reactions show that alkynes (RCCR) attain
      1,2-dicarbene nature during CCR angle bending. Alkyne carbon atoms of bent
      structures exhibit MESP features unique to lone-pair bearing atoms, delta around
      200 ppm typical for carbene centers and large reduction in CC triple bond
      character. Lone pair bearing atoms of R substituents enhance the carbene
      character. The bent alkynes can be trapped with Lewis acids (BH3, BF3, AlF3 and
      AlCl3) as the lone pairs developed on carbon centers provide strong donor type
      dative bonding. The dative bond gives a formal valence electron count six on
      carbon and suggests the for-mation of acceptor type dative bonding to carbon from
      Lewis base (NH3). Reaction of alkynes with (Lewis acid-Lewis base) systems yield
      (Lewis acid)2-Alkyne-Lewis base)2 complexes which are exothermic and exergonic
      for many cases. These complexes are examples of captodative carbon(II) compounds.

PMID- 30192060
TI  - Video-assisted thorascopic lobectomy for pulmonary arteriovenous malformations to
      prevent cerebral abscess.

PMID- 30192061
TI  - Disease progression in a pre-symptomatically treated patient with juvenile-onset
      Pompe disease - need for an earlier treatment?

PMID- 30192063
TI  - Erratum.

PMID- 30192062
TI  - Heterozygous KIDINS220 mutation leads to spastic paraplegia and obesity in an
      Asian girl.

PMID- 30192064
TI  - Multifunctional effects of a modification of SLA titanium implant surface with
      strontium-containing nanostructures on immunoinflammatory and osteogenic cell
      function.
AB  - This study investigated the effects of surface modification of clinically
      available sandblasted/acid-etched (SLA) titanium oral implants with strontium
      (Sr)-containing nanostructures on both early immunoinflammatory macrophage cell
      functions and osteogenic stem cell functions. The goal was to provide insight for
      future surface engineering of titanium implants with multifunctional effects,
      that is, tissue healing capacity at both the nonosteogenic cell centered initial
      stage and the subsequent osteogenic cell-governed later stage-osseointegration
      process. The Sr-containing nanostructure was prepared in on the SLA-type implant
      surface by wet chemical treatment. The results showed that Sr modification is
      favorable for early macrophage cell functions and increases osteogenic capacity
      of the SLA surface. Surface Sr modification notably upregulated regenerative
      macrophage phenotype expression and anti-inflammatory cytokine IL10 production
      while suppressing inflammatory cytokine TNFalpha. Sr incorporation enhanced
      certain early cellular events of ST2 stem cells such as early cellular spreading
      and critical integrin gene expression, which in turn notably increased osteogenic
      differentiation (osteogenesis-related phenotype gene expression and osteocalcin
      production) when combined with the microstructured SLA implant surface. Surface
      modification of SLA-type implants with Sr-containing nanostructures demonstrated
      the ability to favorably influence early immunoinflammatory macrophage cell
      functions and the functionality of osteogenesis cells, resulting in an enhanced
      osseointegration outcome. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res
      Part A: 106A: 3009-3020, 2018.

PMID- 30192065
TI  - Chemical Probes for Human UDP-Glucuronosyltransferases: A Comprehensive Review.
AB  - UGTs play crucial roles in the metabolism and detoxification of both endogenous
      and xenobiotic compounds. The key roles of UGTs in human health have garnered
      great interest in the design and development of specific probes for human UGTs.
      However, in contrast to other human enzymes, the probe substrates for human UGTs
      are rarely reported, owing to the highly overlapping substrate specificities of
      UGTs and the lack of the integrated crystal structures of UGTs. Over the past
      decades, many efforts are made to develop specific probe substrates for UGTs and
      use them in both basic research and drug discovery. This review focuses on recent
      progress in the development of probe substrates for UGTs and their biomedical
      applications. A long list of chemical probes for UGTs, including non-fluorescent
      and fluorescent probes along with their structural information and kinetic
      parameters, are prepared and analyzed. Additionally, challenges and future
      directions in this field are highlighted in the final section. All information
      and knowledge presented in this review provide practical tools/methods for
      measuring UGT activities in complex biological samples, which will be very
      helpful for rapid screening and characterization of UGT modulators, and for
      exploring the relevance of UGT enzymes to human diseases.

PMID- 30192066
TI  - Maternal Red Blood Cell Folate and Infant Vitamin B12 Status Influence
      Methylation of Genes Associated with Childhood Acute Lymphoblastic Leukemia.
AB  - SCOPE: Inadequate maternal folate intake is associated with increased childhood
      acute lymphoblastic leukemia (ALL) risk. Folate provides methyl groups for DNA
      methylation, which is dramatically disrupted in ALL. Whether or not maternal
      folate (and related B-vitamin) intake during pregnancy may affect ALL risk via
      influencing DNA methylation is investigated. METHODS AND RESULTS: Genes in which
      methylation changes are reported both in response to folate status and in ALL are
      investigated. Folate-responsive genes (n = 526) are identified from mouse models
      of maternal folate depletion during pregnancy. Using published data, 2621 genes
      with persistently altered methylation in ALL are identified. Overall 25
      overlapping genes are found, with the same directional methylation change in
      response to folate depletion and in ALL. Hypermethylation of a subset of genes
      (ASCL2, KCNA1, SH3GL3, SRD5A2) in ALL is confirmed by measuring 20 patient
      samples using pyrosequencing. In a nested cohort of cord blood samples (n = 148),
      SH3GL3 methylation is inversely related to maternal RBC folate concentrations (p
      = 0.008). Furthermore, ASCL2 methylation is inversely related to infant vitamin
      B12 levels. (p = 0.016). CONCLUSION: Findings demonstrate proof of concept for a
      plausible mechanism, i.e., variation in DNA methylation, by which low intake of
      folate, and related B-vitamins during pregnancy may influence ALL risk.

PMID- 30192067
TI  - Bilateral chylothorax and pericardial effusion following subtotal gastrectomy in
      a patient with situs inversus totalis.

PMID- 30192068
TI  - Outpatient Engagement Lowers Predicted Risk of Suicide Attempts in Fibromyalgia.
AB  - OBJECTIVE: Fibromyalgia (FM) patients are 10x more likely to die by suicide than
      the general population. The purpose of this study was to externally validate
      published models predicting suicidal ideation and attempts in FM and identify
      interpretable risk and protective factors for suicidality unique to FM. METHODS:
      This is a case-control study of large-scale EHR data collected from 1998-2017,
      identifying FM cases with validated PheKB criteria. Model performance was
      measured through discrimination including area under the receiver operating
      characteristic (AUC), sensitivity, specificity, and through calibration including
      calibration plots. Risk factors were selected by L1-penalized regression with
      bootstrapping for both outcomes. Secondary utilization analyses converted time
      based-billing codes to equivalent minutes to estimate face-to-face provider
      contact. RESULTS: We identified 8,879 individuals with FM, with 34 known suicide
      attempts and 96 documented cases of suicidal ideation. External validity was good
      for both suicidal ideation (AUC=0.80) and attempts (AUC=0.82) and excellent
      calibration. Risk factors specific to suicidal ideation included polysomatic
      complaints such as fatigue (OR=1.29, 95%CI 1.25-1.32), dizziness (OR=1.25, 95%CI
      1.22-1.28), and weakness (OR=1.17, 95%CI 1.15-1.19). Risk factors specific to
      suicide attempt included obesity (OR=1.18, 95%CI 1.10-1.27) and drug dependence
      (OR=1.15, 95%CI 1.12-1.18). Per utilization analyses, those with FM and no
      suicidal ideation spent 3.5x more time in follow-up annually, and those without
      documented suicide attempts spent over 40x more time face-to-face with providers
      annually. CONCLUSION: This is the first study to successfully apply machine
      learning to reliably detect suicidality in FM, identifying novel risk factors for
      suicidality and highlighting outpatient engagement as a protective factor against
      suicide. This article is protected by copyright. All rights reserved.

PMID- 30192069
TI  - A Novel Ultrasound Image Acquisition Protocol and Scoring System for the
      Pediatric Knee.
AB  - OBJECTIVE: The use of musculoskeletal ultrasound is increasing among pediatric
      rheumatologists. Reliable scoring systems are needed for the objective assessment
      of synovitis. The aims of this study were: 1) to create a standardized and
      reproducible image acquisition protocol for B-Mode and Doppler ultrasound of the
      pediatric knee; and 2) to develop a standardized scoring system and determine its
      reliability for pediatric knee synovitis. METHODS: Six pediatric rheumatologists
      developed a set of standard views for knee assessment in children with juvenile
      arthritis. After a comprehensive literature review, practical exercises and a
      consensus process were performed. A scoring system for both B-Mode and Doppler
      was then developed and assessed for reliability. Inter-reader reliability or
      agreement among a total of 16 raters was determined using two-way single-score
      intraclass correlation coefficients analysis (ICC). RESULTS: Twenty-one views to
      assess knee arthritis were initially identified. Following completion of
      practical exercises and subsequent consensus processes, a total of 3 views in
      both B-mode and Doppler were selected: suprapatellar longitudinal and
      medial/lateral parapatellar transverse views. Several rounds of scoring and
      modifications resulted in a final ICC of: suprapatellar view B-mode 0.89 (95% CI
      0.86-0.92), Doppler 0.55 (0.41-0.69); medial parapatellar view B-mode 0.76 (0.68
      0.83), Doppler 0.75 (0.66-0.83); and lateral parapatellar view B-mode 0.82 (0.75
      0.88), Doppler 0.76 (0.66-0.84). CONCLUSION: A novel B-Mode and Doppler image
      acquisition and scoring system for assessing synovitis in the pediatric knee was
      successfully developed through practical exercises and consensus process. Study
      results demonstrate overall good to excellent reliability. This article is
      protected by copyright. All rights reserved.

PMID- 30192070
TI  - Mobile phone text messages improve treatment adherence in patients taking
      methotrexate for rheumatoid arthritis: a randomized pilot study.
AB  - OBJECTIVES: To assess the impact of weekly text messages on adherence in patients
      taking methotrexate (MTX) for rheumatoid arthritis (RA). METHODS: This
      prospective, randomized pilot, single-site study included RA patients stabilized
      on MTX combined or not with biologics. Participants were randomized to three
      interventions: a standard consultation (controls), a 15-min pharmacist-led
      counselling session or the receipt of text message reminders. The change over
      time in the Compliance Questionnaire Rheumatology (CQR-19) score between baseline
      and 6 months was defined as the primary outcome for adherence. Multivariable
      analyses and final adherence (as a composite outcome of the CQR-19 score, the
      Girerd score and the medication possession ratio) were probed in sensitivity
      tests. Rheumatologic scales, inflammation, and patient satisfaction were also
      analyzed. RESULTS: 96 patients (mean+/-standard deviation DAS-28: 2.42+/-1.03)
      were monitored. The change over time in the CQR-19 score was significantly higher
      in the text message group (3.32+/-5.66; p=0.02) than in the control (0.22+/-6.56)
      and the pharmacist-led counselling group (-0.14+/-7.56). Multivariable logistic
      regression showed that text messages remained associated with an increase in the
      CQR-19 score, independently of the baseline CQR-19 score (odds ratio [95%
      confidence interval]: 3.63 [1.26-10.49]; p=0.017). In the text message group, the
      increase in the CQR-19 score was correlated with the Health Assessment
      Questionnaire score (r = -0.405; p=0.021), and patient satisfaction was
      significantly higher (p<0.01) than in control group. CONCLUSION: Our results
      evidenced a positive impact of text messages on adherence to MTX treatment for
      RA. The clinical benefit and the ideal target patient remain to be determined.
      This article is protected by copyright. All rights reserved.

PMID- 30192071
TI  - Disease activity of psoriatic arthritis during and after pregnancy: A prospective
      multicenter study.
AB  - OBJECTIVE: To study disease activity in women with peripheral psoriatic arthritis
      (PsA) during and after pregnancy. Previous knowledge on this topic is sparse.
      METHODS: The study included 108 pregnancies in 103 women with PsA from a
      Norwegian nationwide register. Disease activity was assessed prospectively at
      seven time points before, throughout and after pregnancy with the disease
      activity scores DAS28-CRP-3 and BASDAI. Scores assessed at each time point were
      analyzed in a linear mixed model. We did additional analyses with "tumor necrosis
      factor inhibitor (TNFi) in pregnancy" as covariate. The same statistical method
      was used to study self-reported physical function, pain and mental health.
      RESULTS: About 75% of the women were in remission or had low disease activity
      during and after pregnancy according to DAS28. Although altogether stable, we
      found that disease activity decreased in pregnancy and increased within six
      months postpartum. Disease activity six months postpartum was significantly
      higher than six weeks postpartum (mean DAS28 2.71 vs. 2.45, p=0.016). Women using
      TNFi in pregnancy had significantly lower disease activity than women not using
      TNFi (mean DAS28 six months postpartum 2.22 vs. 2.72, p=0.043). BASDAI-scores
      were also low and stable, but significantly higher six months postpartum than six
      weeks postpartum (mean BASDAI 3.69 vs. 2.95, p=0.013). CONCLUSION: Studying women
      with PsA, we found that disease activity was highest six months postpartum, but
      altogether low and stable in the period from planning pregnancy to one year after
      delivery. Women using TNFi in pregnancy had significantly lower disease activity.
      This article is protected by copyright. All rights reserved.

PMID- 30192072
TI  - Diffuse Idiopathic Skeletal Hyperostosis and Ankylosing Spondylitis. Comment on
      the article by Latourte et al.
AB  - We read with great interest the article by Latourte et al about axial
      spondyloarthritis (SpA) like imaging in Diffuse Idiopathic Skeletal Hyperostosis
      (DISH) (1). On the spine magnetic resonance imaging, 76.9% of their cohort of
      patients with symptomatic DISH had at least 1 inflammatory lesion, as assessed by
      bone medullar edema (BME). As soft tissue edema, BME may be caused by mechanical
      stress or by inflammation (2). Mechanical stress is implicated in the
      pathogenesis of DISH. This article is protected by copyright. All rights
      reserved.

PMID- 30192074
TI  - The Robot: a big disappointment, or just early days?

PMID- 30192076
TI  - Commentary: Reply to 'Accrediting colonoscopy services and colonoscopists for
      screening makes a difference'.

PMID- 30192079
TI  - Commentary: Accrediting colonoscopy services and colonoscopists for screening
      makes a difference.

PMID- 30192080
TI  - Response to: "Diffuse Idiopathic Skeletal Hyperostosis and Ankylosing
      Spondylitis. Comment on the article by Latourte et al" by Olmedo-Garzon and Ruiz
      Ollero.
AB  - We would like to thank F.J. Olmedo-Garzon and A. Ruiz-Ollero for their interest
      in our article examining the presence of imaging features suggestive of axial
      spondyloarthritis (axSpA) in patients with diffuse idiopathic skeletal
      hyperostosis (DISH) (1). We have read with great interest their comments on our
      results indicating a high prevalence of inflammatory lesions (especially bone
      marrow edema [BME]) at the spine but not at the sacro-iliac joints (SIJ) (2).
      Similar findings have been observed recently in the ILOS-DESIR study, comparing
      age-matched patients with recent onset chronic back pain (n=97) vs. recent onset
      axSpA (n=100). This article is protected by copyright. All rights reserved.

PMID- 30192081
TI  - HiTOP must meet the use requirements of the ICD before it can aspire to replace
      it.

PMID- 30192082
TI  - Diet as a hot topic in psychiatry: a population-scale study of nutritional intake
      and inflammatory potential in severe mental illness.

PMID- 30192083
TI  - Strengthening the scientific backbone of the WPA.

PMID- 30192084
TI  - The brain's center of gravity: how the default mode network helps us to
      understand the self.

PMID- 30192085
TI  - Internalizing disorders: the whole is greater than the sum of the parts.

PMID- 30192086
TI  - Conditioned hallucinations: historic insights and future directions.

PMID- 30192089
TI  - Balancing validity, utility and public health considerations in disorders due to
      addictive behaviours.

PMID- 30192088
TI  - Tardive dyskinesia risk with first- and second-generation antipsychotics in
      comparative randomized controlled trials: a meta-analysis.
AB  - Tardive dyskinesia (TD) risk with D2/serotonin receptor antagonists or D2
      receptor partial agonists (second-generation antipsychotics, SGAs) is considered
      significantly lower than with D2 antagonists (first-generation antipsychotics,
      FGAs). As some reports questioned this notion, we meta-analyzed randomized
      controlled studies (RCTs) to estimate the risk ratio (RR) and annualized rate
      ratio (RaR) of TD comparing SGAs vs. FGAs and SGAs vs. SGAs. Additionally, we
      calculated raw and annualized pooled TD rates for each antipsychotic. Data from
      57 head-to-head RCTs, including 32 FGA and 86 SGA arms, were meta-analyzed,
      yielding 32 FGA-SGA pairs and 35 SGA-SGA pairs. The annualized TD incidence
      across FGA arms was 6.5% (95% CI: 5.3-7.8%) vs. 2.6% (95% CI: 2.0-3.1%) across
      SGA arms. TD risk and annualized rates were lower with SGAs vs. FGAs (RR=0.47,
      95% CI: 0.39-0.57, p<0.0001, k=28; RaR=0.35, 95% CI: 0.28-0.45, p<0.0001, number
      needed-to-treat, NNT=20). Meta-regression showed no FGA dose effect on FGA-SGA
      comparisons (Z=-1.03, p=0.30). FGA-SGA TD RaRs differed by SGA comparator
      (Q=21.8, df=7, p=0.003), with a significant advantage of olanzapine and
      aripiprazole over other non-clozapine SGAs in exploratory pairwise comparisons.
      SGA-SGA comparisons confirmed the olanzapine advantage vs. non-clozapine SGAs
      (RaR=0.66, 95% CI: 0.49-0.88, p=0.006, k=17, NNT=100). This meta-analysis
      confirms a clinically meaningfully lower TD risk with SGAs vs. FGAs, which is not
      driven by high dose FGA comparators, and documents significant differences with
      respect to this risk between individual SGAs.

PMID- 30192091
TI  - Why are savant skills and special talents associated with autism?

PMID- 30192092
TI  - After the failure of DSM: clinical research on psychiatric diagnosis.

PMID- 30192087
TI  - Intergenerational transmission of trauma effects: putative role of epigenetic
      mechanisms.
AB  - This paper reviews the research evidence concerning the intergenerational
      transmission of trauma effects and the possible role of epigenetic mechanisms in
      this transmission. Two broad categories of epigenetically mediated effects are
      highlighted. The first involves developmentally programmed effects. These can
      result from the influence of the offspring's early environmental exposures,
      including postnatal maternal care as well as in utero exposure reflecting
      maternal stress during pregnancy. The second includes epigenetic changes
      associated with a preconception trauma in parents that may affect the germline,
      and impact fetoplacental interactions. Several factors, such as sex-specific
      epigenetic effects following trauma exposure and parental developmental stage at
      the time of exposure, explain different effects of maternal and paternal trauma.
      The most compelling work to date has been done in animal models, where the
      opportunity for controlled designs enables clear interpretations of transmissible
      effects. Given the paucity of human studies and the methodological challenges in
      conducting such studies, it is not possible to attribute intergenerational
      effects in humans to a single set of biological or other determinants at this
      time. Elucidating the role of epigenetic mechanisms in intergenerational effects
      through prospective, multi-generational studies may ultimately yield a cogent
      understanding of how individual, cultural and societal experiences permeate our
      biology.

PMID- 30192093
TI  - Mental health initiatives in the workplace: models, methods and results from the
      Mental Health Commission of Canada.

PMID- 30192090
TI  - Clinical utility of ICD-11 diagnostic guidelines for high-burden mental
      disorders: results from mental health settings in 13 countries.
AB  - In this paper we report the clinical utility of the diagnostic guidelines for ICD
      11 mental, behavioural and neurodevelopmental disorders as assessed by 339
      clinicians in 1,806 patients in 28 mental health settings in 13 countries.
      Clinician raters applied the guidelines for schizophrenia and other primary
      psychotic disorders, mood disorders (depressive and bipolar disorders), anxiety
      and fear-related disorders, and disorders specifically associated with stress.
      Clinician ratings of the clinical utility of the proposed ICD-11 diagnostic
      guidelines were very positive overall. The guidelines were perceived as easy to
      use, corresponding accurately to patients' presentations (i.e., goodness of fit),
      clear and understandable, providing an appropriate level of detail, taking about
      the same or less time than clinicians' usual practice, and providing useful
      guidance about distinguishing disorder from normality and from other disorders.
      Clinicians evaluated the guidelines as less useful for treatment selection and
      assessing prognosis than for communicating with other health professionals,
      though the former ratings were still positive overall. Field studies that assess
      perceived clinical utility of the proposed ICD-11 diagnostic guidelines among
      their intended users have very important implications. Classification is the
      interface between health encounters and health information; if clinicians do not
      find that a new diagnostic system provides clinically useful information, they
      are unlikely to apply it consistently and faithfully. This would have a major
      impact on the validity of aggregated health encounter data used for health policy
      and decision making. Overall, the results of this study provide considerable
      reason to be optimistic about the perceived clinical utility of the ICD-11 among
      global clinicians.

PMID- 30192095
TI  - Action Plan of the WPA Secretary for Publications.

PMID- 30192096
TI  - Classification of psychopathology: conceptual and historical background.

PMID- 30192097
TI  - Telemental health: why the revolution has not arrived.

PMID- 30192098
TI  - The dialectic of quantity and quality in psychopathology.

PMID- 30192099
TI  - Global trends in high impact psychiatry research.

PMID- 30192100
TI  - Serotonin, psychedelics and psychiatry.

PMID- 30192094
TI  - Management of common adverse effects of antipsychotic medications.
AB  - The benefits of antipsychotic medications are sometimes obscured by their adverse
      effects. These effects range from relatively minor tolerability issues (e.g.,
      mild sedation or dry mouth) to very unpleasant (e.g., constipation, akathisia,
      sexual dysfunction) to painful (e.g., acute dystonias) to disfiguring (e.g.,
      weight gain, tardive dyskinesia) to life-threatening (e.g., myocarditis,
      agranulocytosis). Importantly, adverse effect profiles are specific to each
      antipsychotic medication and do not neatly fit into first- and second-generation
      classifications. This paper reviews management strategies for the most frequent
      side effects and identifies common principles intended to optimize net
      antipsychotic benefits. Only use antipsychotics if the indication is clear; only
      continue antipsychotics if a benefit is discernible. If an antipsychotic is
      providing substantial benefit, and the adverse effect is not life-threatening,
      then the first management choice is to lower the dose or adjust the dosing
      schedule. The next option is to change the antipsychotic; this is often
      reasonable unless the risk of relapse is high. In some instances, behavioral
      interventions can be tried. Finally, concomitant medications, though generally
      not desirable, are necessary in many instances and can provide considerable
      relief. Among concomitant medication strategies, anticholinergic medications for
      dystonias and parkinsonism are often effective; beta-blockers and anticholinergic
      medications are useful for akathisia; and metformin may lead to slight to
      moderate weight loss. Anticholinergic drops applied sublingually reduce
      sialorrhea. Usual medications are effective for constipation or dyslipidemias.
      The clinical utility of recently approved treatments for tardive dyskinesia,
      valbenazine and deutetrabenazine, is unclear.

PMID- 30192103
TI  - Digital phenotyping: a global tool for psychiatry.

PMID- 30192102
TI  - Dimensions fit the data, but can clinicians fit the dimensions?

PMID- 30192101
TI  - Psychological interventions to reduce positive symptoms in schizophrenia:
      systematic review and network meta-analysis.
AB  - Psychological treatments are increasingly regarded as useful interventions for
      schizophrenia. However, a comprehensive evaluation of the available evidence is
      lacking and the benefit of psychological interventions for patients with current
      positive symptoms is still debated. The present study aimed to evaluate the
      efficacy, acceptability and tolerability of psychological treatments for positive
      symptoms of schizophrenia by applying a network meta-analysis approach, that can
      integrate direct and indirect comparisons. We searched EMBASE, MEDLINE, PsycINFO,
      PubMed, BIOSIS, Cochrane Library, World Health Organization's International
      Clinical Trials Registry Platform and ClinicalTrials.gov for randomized
      controlled trials of psychological treatments for positive symptoms of
      schizophrenia, published up to January 10, 2018. We included studies on adults
      with a diagnosis of schizophrenia or a related disorder presenting positive
      symptoms. The primary outcome was change in positive symptoms measured with
      validated rating scales. We included 53 randomized controlled trials of seven
      psychological interventions, for a total of 4,068 participants receiving the
      psychological treatment as add-on to antipsychotics. On average, patients were
      moderately ill at baseline. The network meta-analysis showed that cognitive
      behavioural therapy (40 studies) reduced positive symptoms more than inactive
      control (standardized mean difference, SMD=-0.29; 95% CI: -0.55 to -0.03),
      treatment as usual (SMD=-0.30; 95% CI: -0.45 to -0.14) and supportive therapy
      (SMD=-0.47; 95% CI: -0.91 to -0.03). Cognitive behavioural therapy was associated
      with a higher dropout rate compared with treatment as usual (risk ratio, RR=0.74;
      95% CI: 0.58 to 0.95). Confidence in the estimates ranged from moderate to very
      low. The other treatments contributed to the network with a lower number of
      studies. Results were overall consistent in sensitivity analyses controlling for
      several factors, including the role of researchers' allegiance and blinding of
      outcome assessor. Cognitive behavior therapy seems to be effective on positive
      symptoms in moderately ill patients with schizophrenia, with effect sizes in the
      lower to medium range, depending on the control condition.

PMID- 30192104
TI  - "Throwing out the baby with the bathwater"? Conceptual and methodological
      limitations of the HiTOP approach.

PMID- 30192106
TI  - Healthy pregnancy and prevention of psychosis.

PMID- 30192105
TI  - Global mental health: how are we doing?

PMID- 30192107
TI  - Categorical and/or continuous? Learning from vascular surgery.

PMID- 30192108
TI  - WPA Secretary for Education work plan.

PMID- 30192109
TI  - Quantitative classification as (re-)descriptive psychopathology.

PMID- 30192111
TI  - Advocacy 101: Engaging Rheumatology Fellows in Health Policy and Advocacy.
AB  - OBJECTIVE: Rheumatology fellowship programs lack formal curricular content to
      educate trainees about legislative and regulatory healthcare policies that have a
      profound impact on academic and community practices. Advocacy 101 was created as
      a program to address this gap and engage fellows-in-training (FIT) in health
      advocacy efforts. METHODS: A web-based survey was sent via the American College
      of Rheumatology (ACR) FIT listserve in July 2015 and April 2016. The survey
      queried respondents about their knowledge of and participation in health policy
      and advocacy. Survey results guided the design of an educational program called
      Advocacy 101 for FIT and program directors in conjunction with the ACR Advocates
      for Arthritis fly-in. RESULTS: The survey response rate increased from 19% (95 of
      500) to 39% (231 of 595) of FIT between 2015 and 2016. In 2015 the top reason
      (64%) for non-participation in health policy and advocacy efforts was lack of
      knowledge on how to get involved. This decreased to 39% of respondents in 2016.
      Other barriers to participation included lack of time and familiarity with the
      issues. Over the two years, FIT identified patient access to medication and
      insurance and physician reimbursement as important advocacy issues. All
      participants of Advocacy 101 reported an increase in knowledge of health policy
      and the intent to stay involved. CONCLUSION: FIT regard health policy issues as
      important, however many are uncertain of how to participate in advocacy. Advocacy
      101 is the first program designed to educate and engage rheumatology FIT in
      health policy and advocacy endeavors. This article is protected by copyright. All
      rights reserved.

PMID- 30192112
TI  - ENDOPLASMIC RETICULUM STRESS IN DIABETIC RETINOPATHY AND THE APPROACHES TO ITS
      CORRECTION.
AB  - Diabetic retinopathy (DR) is one of the most common complications of diabetes
      mellitus (DM). Among the molecular mechanisms leading to the development of DR,
      the endoplasmic reticulum (ER) stress that is identified in DM in retinal neurons
      and in pericytes of retinal capillaries plays an important role. Abnormalities in
      the folding and maturation of proteins in ER trigger the ER specific response,
      referred as the unfolded protein response (UPR), which induces protein refolding
      or degradation. Currently, there are three main UPR-pathways that include
      inositol-requiring enzyme-1 (IRE1), transcription factor-6 (ATF6) and sensory
      kinase PERK as the sensor components, all of which are involved in the
      pathological changes in the retina at DR, inducing the inflammation, apoptosis
      and vascular impairment therein. In the review, the functional changes in IRE1-,
      ATF6and PERK-dependent UPR-pathways in diabetic retina, as well as factors that
      contribute to the development of ER stress in retinal cells including pro
      inflammatory factors, vascular endothelial growth factor and intercellular
      adhesion molecules are considered. The approaches to ER stress correction in
      diabetic retina, which include the use of low-molecular chaperones, such as
      fenofibric acid, increased activity of chaperone-like p58IPK protein, and the
      restoration of activity of retinal hormonal signaling systems, whose functions
      are violated in DR, are discussed.

PMID- 30192113
TI  - ROLE OF P38 MAP-KINASE IN THE STRESS-INDUCED SENESCENCE PROGRESSION OF HUMAN
      ENDOMETRIUM-DERIVED MESENCHYMAL STEM CELLS.
AB  - Our recent findings clearly demonstrate that human endometrium-derived
      mesenchymal stem cells (hMESCs) respond to the sublethal oxidative stress by the
      premature senescence induction via AOI/Chk2/p53/ p21/Rb pathway. Furthermore,
      based on the application of the SB203580 (SB) we suggested p38 MAP-kinase
      involvement in senescence progression. However, there are several disadvantages
      concerning this inhibitor: 1) using SB would not be suitable for in vivo
      experiments due to toxicity issue; 2) the poor kinase selectivity profile of SB
      complicates interpretation of the obtained data. Here, in order to confirm the
      implication of p38 in the H2O2-induced senescence of hMESCs, we applied another
      highly specific inhibitor of p38 - BIRB796 (BIRB). In presence of BIRB we
      revealed cell size decrease, reduction in the levels of reactive oxygen species,
      partial restoration of proliferation and increase in Rb phosphorylation levels in
      comparison to H2O2-treated hMESCs. Summarizing the obtained results we can
      postulate p38 implication in H2O2-induced senescence of hMESCs, and suggest p38
      inhibition as a promising approach in prevention of premature senescence.

PMID- 30192114
TI  - REGULATION OF VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF) PRODUCTION BY MOUSE
      THYMIC EPITHELIAL CELL LINES.
AB  - Vascular endothelial growth factor (VEGF) is synthesized in small amounts by
      thymus epithelial cells in adults and plays a role in supporting vascular
      homeostasis. However its role becomes dramatically important during the process
      of thymus reparation after involution caused by chemo-, x-ray or hormonal
      therapy. The aim of the study was to evaluate the influence of different factors
      on VEGF production by mouse thymic epithelial cells in vitro. As a model two cell
      lines were used: cortical cTEC1-2 and medullar mTEC3-10 cells. These cells were
      characterized by their ability to synthesize VEGF mRNA and protein as well as by
      their expression of VEGF receptors. VEGFR1 and VEGFR2 mRNA expression in these
      cells were absent while NRP-1 mRNA revealed low level of expression. It was shown
      by ELISA that cTEC1-2 cells produced VEGF about 30 times more than mTEC3-10. When
      cultivated in the presence of cytokines, hormonal factors or thymocytes, both
      cell lines responded differently. Introduction of keratinocyte growth factor
      (KGF) induced VEGF mRNA expression as well as VEGF production in medullar cells
      but simultaneously down-regulated VEGF mRNA expression in cortical cells.
      Dexamethasone suppressed mRNA VEGF expression and VEGF production in cortical
      cells while in medullar cells only VEGF production was reduced. Introduction of
      IL-7, IL-1b or murine thymocytes increased while addition of Semaphorin 3A, SDF
      1a or ACTH decreased VEGF production by cortical epithelial cells with no
      influence on medullar cells. We suggest that our data obtained in vitro can be
      used for further development of special programs for directed regulation of VEGF
      synthesis in the thymus epithelial cells in the vivo.

PMID- 30192115
TI  - FLUORESCENT MICROSCOPY IDENTIFICATION OF THE EXPRESSION OF a2 AND b1 NA +/K+
      ATPase, a1S (L-TYPE), NA2+-CHANNEL, SERCA 1/2/3 CA2+-ATPase SUBUNITS AT FAST AND
      SLOW MUSCLES IN THE HYPOGRAVITY MODELING EXPERIMENTS IN RATS
AB  - The experiments of modeling hypogravity using fluorescent microscopy have shown a
      decrease of expression of b1 of Na +/K+-ATPase and Ca2+-ATPase subunits and the
      increase in the insensitivity of synthesis of a1S subunit of the L-type Ca2+
      channel of the plasmatic membrane, whereas the synthesis of a2 subunit of Na+/K+
      ATPase does not change. In "fast" muscle only observed similar for "slow" muscle
      decrease in the expression of b1 subunit without changing other parameters were
      studied. However, the decrease in fluorescence b1 subunit due to spread of data
      was not statistically significant. Thus hypogravity adversely affects the
      functioning primarily skeletal muscles, providing static load.

PMID- 30192110
TI  - The severity of psychiatric disorders.
AB  - The issue of the severity of psychiatric disorders has great clinical importance.
      For example, severity influences decisions about level of care, and affects
      decisions to seek government assistance due to psychiatric disability.
      Controversy exists as to the efficacy of antidepressants across the spectrum of
      depression severity, and whether patients with severe depression should be
      preferentially treated with medication rather than psychotherapy. Measures of
      severity are used to evaluate outcome in treatment studies and may be used as
      meaningful endpoints in clinical practice. But, what does it mean to say that
      someone has a severe illness? Does severity refer to the number of symptoms a
      patient is experiencing? To the intensity of the symptoms? To symptom frequency
      or persistence? To the impact of symptoms on functioning or on quality of life?
      To the likelihood of the illness resulting in permanent disability or death?
      Putting aside the issue of how severity should be operationalized, another
      consideration is whether severity should be conceptualized similarly for all
      illnesses or be disorder specific. In this paper, we examine how severity is
      characterized in research and contemporary psychiatric diagnostic systems, with a
      special focus on depression and personality disorders. Our review shows that the
      DSM-5 has defined the severity of various disorders in different ways, and that
      researchers have adopted a myriad of ways of defining severity for both
      depression and personality disorders, although the severity of the former was
      predominantly defined according to scores on symptom rating scales, whereas the
      severity of the latter was often linked with impairments in functioning. Because
      the functional impact of symptom-defined disorders depends on factors extrinsic
      to those disorders, such as self-efficacy, resilience, coping ability, social
      support, cultural and social expectations, as well as the responsibilities
      related to one's primary role function and the availability of others to assume
      those responsibilities, we argue that the severity of such disorders should be
      defined independently from functional impairment.

PMID- 30192116
TI  - THE KARYOSPHERE CAPSULE IN OOCYTES OF HIBERNATING FROGS RANA TEMPORARIA CONTAINS
      ACTIN, LAMINS AND SMALL NUCLEAR RNP.
AB  - The nuclei of late vitellogenic oocytes of hibernating frogs Rana temporaria were
      studied. During the studied period of oogenesis, chromosomes are significantly
      inactivated and surrounded by a fibrillar karyosphere capsule. Formation of the
      karyosphere capsule in the grass frog oocytes was previously investigated in
      detail at the light and electron microscopic levels, but the molecular
      composition of the capsule still remains uncertain. Immunofluorescent staining of
      whole-mount preparations of oocyte nuclei revealed the following proteins in the
      karyosphere capsule: actin, lamins A, C and B, and the Sm proteins of snRNPs. A
      putative role of these proteins in formation of the karyosphere capsule is
      discussed.

PMID- 30192117
TI  - BIORESORBABLE PROPERTIES OF CHITOSAN FIBERS IN ENDOMYSIUM AND PERIMYSIUM MUSCLE
      TISSUE
AB  - Scanning electron microscopy and histologic analysis were used in the comparative
      in vivo study of resorption of chitosan fibers implanted into endomysium and
      perimysium of a rat latissimus dorsi muscle. It was demonstrated that the
      mechanism and rate of chitosan fiber resorption depend on the position of fibers
      in muscular tissue. After implantation of chitosan fibers into endomysium (when
      chitosan was in direct contact with muscle fibers), the formation of cross
      sectional cracks, fragmentation of implanted fibers and its partial resorption
      were observed in 14 days. Complete chitosan resorption in endomysium occurred
      after 30 days only. Chitosan fibers implanted into perimysium preserved integrity
      for 7 days, and fibrous tissue was formed around implants. After 45 days of
      exposure, no signs of chitosan fiber destruction were registered in this case.
      Biocompatibility of chitosan fibers proved by effective adhesion and
      proliferation of mesenchymal stem cells on their surface.

PMID- 30192118
TI  - STABILITY OF THE GELS BASED ON TYPE I COLLAGEN AND HYALURONIC ACID.
AB  - Development of hyaluronic acid (HA) supplemented biomaterials for regenerative
      medicine is complicated with easy water solubility of HA. It results in decreased
      stability of HA-based scaffolds that, consequently, initiated search for
      crosslinking techniques intended to retain HA within a scaffold. In this study,
      gels composed of type I collagen and native high molecular weight HA were
      prepared and their stability in buffer solutions has been evaluated. Fibronectin
      and human dermal fibroblasts were incorporated into gels as biological linkages
      for HA instead of chemical agents. Gel stability was estimated based on HA
      diffusion toward a buffer solution. In addition, HA and HA-supplemented gels
      resistance to fetal calf serum (FSC) as a part of cultural media for fibroblasts
      has been studied and no degradation of HA by serum hyaluronidase has been
      detected under the experimental conditions. The results showed that HA diffuses
      from collagen gels within 1-3 days. Neither fibronectin nor fibroblasts added
      separately prevent HA diffusion. But if gels were inoculated with fibroblasts
      together with fibronectin, more HA was left in the gels according to alcian blue
      staining. Agarose gel electrophoresis has shown that conditioned media collected
      from such gels are enriched with HA that differs from the initial one in that it
      contains a new portion of HA with higher molecular weight. It is concluded that
      HA-supplemented collagen gels are not stable in buffer solutions but fibroblasts
      incorporated into such gels synthesize significant amount of HA under the
      influence of fibronectin and partly compensate the loss of HA due to diffusion.

PMID- 30192119
TI  - BENIGN AND PATHOLOGICAL GAIN OR LOSS OF GENETIC MATERIAL - ABOUT MICROSCOPIC AND
      SUBMICROSCOPIC COPY NUMBER VARIATIONS (CNVs) IN HUMAN GENETICS.
AB  - Submicroscopic gains or losses of chromosomal material are known as copy number
      variations (CNVs). Such CNVs are either connected with a disease or can also be
      (much more frequently) just a manifestation of human's genetic range of
      variation. Besides cytogenetic visible copy number variations (CG-CNVs) first
      discovered as chromosomal heteromorphisms, and later e. g. as euchromatic
      variants (EVs), there are also submicroscopic CNVs (MG-CNVs). Especially the
      latter may be a headache for diagnostics as the same MG-CNV may be found in
      clinically healthy and diseased persons. A so-called two-hit model has been
      introduced to solve this puzzle. As this considers the number of CNVs present
      overall in a genome the question arises if CG-CNVs are considered enough in
      routine cytogenetic as well as MG-CNVs in array-comparative genomic hybridization
      analysis.

PMID- 30192120
TI  - NEUROGENIC NICHE OF THE ADULT MAMMALIAN BRAIN.
AB  - At the moment, the main location of the regional areas of neural stem cells in
      the adult brain is considered to be subventricular zone of the lateral ventricles
      and the dentate gyrus of the hippocampal formation. However, the neural stem
      cells are not located chaotic in these areas, and they are localized in special
      niches - structural microenvironment that enables them to maintain identity,
      affect its proliferation and the fate of her descendants. The components of this
      microenvironment are intercellular interactions, the relationship with the blood
      vessels, extracellular matrix and specialized areas of basement membrane. The
      article describes of the neurogenic niches and the mechanisms controlling cell
      division and differentiation of progenitor cells.

PMID- 30192121
TI  - HUMAN KARYOTYPE ANALYSIS IN DIAGNOSIS VERIFICATION.
AB  - When analyzing a patient's karyotype using classic cytogenetic tools, clinical
      cytogeneticists frequently face a problem of whether the observed morphological
      variant of a chromosome is the norm or pathology. Here we present three cases,
      when the use of additional approaches allowed us to accurately and reliably
      describe the chromosomal abnormalities and to provide a substantiated medical and
      genetic prognosis. Translocations were preliminary diagnosed in the first two
      patients. This opinion was subsequently challenged, as these patients were the
      carriers of rare variants of normal chromosome polymorphisms (21pstkstkpss and
      20cenh+). Thus, these diagnostic measures helped the wife of the first patient to
      maintain the pregnancy, whereas the second patient was referred for IVF. In the
      third case, the preliminary diagnosis trisomy of chromosome 22 has not been
      confirmed. This patient turned out to be a carrier of a supernumerary marker
      chromosome invdup(15)(q13), which offers a much more favorable medical prognosis.

PMID- 30192122
TI  - MOLECULAR KARYOTYPING BY USING CELL-FREE DNA FROM HUMAN BLASTOCOELE FLUID,
      EMBRYOBLAST AND TROPHOBLAST CELLS.
AB  - In the present study, we have carried out a comparative analysis of molecular
      karyotypes of cell free DNA from blastocoele fluid, trophectoderm and inner cell
      mass of human blastocysts at the preimplantation stages of development, using the
      comparative genomic hybridization. Different types of chromosomal abnormalities
      distribution between trophectoderm, inner cell mass and blastocoele fluid were
      identified. It was first shown that the source of cell free DNA in the
      blastocoele fluid may arise from the cells of inner cell mass in addition to the
      trophectoderm cells, which are traditionally used in preimplantation genetic
      diagnosis of chromosomal aberrations. These results support the promising of
      blastocentesis as a new technology of preimplantation genetic diagnosis, which
      provides the possibility of integral analysis of chromosome abnormalities in
      different cells of the blastocyst.

PMID- 30192123
TI  - ECTOPIC TETHERING OF THE CHROMATOR PROTEIN IN UASDBD(GAL4) SYSTEM AS APPROACH FOR
      STUDYING OF THE INSULATOR PROTEINS IN DROSOPHILA MELANOGASTER POLYTENE
      CHROMOSOMES.
AB  - Chromatin insulator proteins are one of the major components that determine the
      domain organization of the genome. According to the latest data, they can mark
      the boundaries of topological domains and prevent the spread of silent chromatin
      to adjacent areas. One approach to the analysis of the actions of these proteins
      is to use the ectopic involvement in the UAS>DBD(GAL4). The method allows to
      evaluate the effect of selected protein in chromatin organization, to establish
      its association with other insulator proteins and influence on the processes of
      transcription and replication. and influence the processes of transcription and
      replication. In this study, we have developed and tested the functionality of the
      system components in ectopic tethering of the Chromator (Chriz) to the region of
      intercalary heterochromatin 10A1-2. Preliminary data have been obtained showing
      that ectopically tethered Chromator to the band 10A1-2 can induce a partial
      decompactization of the band chromatin. Further use of this experimental model
      provides the opportunity to investigate the effect of insulator proteins on the
      chromatin structure.

PMID- 30192124
TI  - Photoluminescence Lifetime of Black Phosphorus Nanoparticles and Their
      Applications in Live Cell Imaging.
AB  - Black phosphorus (BP) has attracted much attention as a new member of 2D
      materials due to its unique electronic and optical properties and a wide range of
      promising applications. Here, for the first time, we report the photoluminescence
      lifetime of BP nanomaterial and its applications as an efficient agent for live
      cell imaging. With a lateral size of ~35 nm and a thickness of ~6 nm, the
      fabricated BP nanoparticles (BPNPs) exhibited a unique photoluminescent (PL)
      emission at ~690 nm. The photoluminescence lifetime (PLT) of BPNPs was determined
      to be 110.5 ps. Coating a layer of mesoporous silica on the surface of BPNPs
      (BPNPs@mSiO2) extended the lifetime to 267 ps, suggesting a change in the
      microenvironment. The lifetime was also influenced by ionic strength and
      intracellular microenvironment, which implies BPNPs as valuable probes for
      sensing variations in the microenvironment. Live cell imaging was achieved via
      directly probing the photoluminescence intensity or the photoluminescence
      lifetime. Our findings are significant, implying that BPNPs can be of large value
      in sensing variations of the cellular microenvironment and in probing cells with
      distinct cytosolic contents. This research leads to promising prospects for BPNPs
      in multiple biomedical applications.

PMID- 30192125
TI  - Wearable Thermoelectric Devices Based on Au-Decorated Two-Dimensional MoS2.
AB  - Two-dimensional (2D) materials have recently opened a new avenue to flexible
      thermoelectric materials with enhanced performance because of their unique
      electronic transport properties. Here, we report a feasible approach to improve
      the thermoelectric performance of transition-metal dichalcogenides by effectively
      decorating 2D MoS2 with Au nanoparticles using in situ growth. The present Au
      decorated MoS2-assembled heterojunction system shows a certain decoupled
      phenomenon, that is, the Seebeck coefficient and conductivity increased
      simultaneously. This is due to the occurrence of p-type doping of the MoS2 2H
      phase and injection energy filtering of dopant-originated carriers around the
      local band bending at the interface. The composite flexible films can achieve a
      power factor value of 166.3 MUW m-1 K-2 at room temperature, which have great
      potential for harvesting human body heat.

PMID- 30192126
TI  - Ultrasound-Excited Protoporphyrin IX-Modified Multifunctional Nanoparticles as a
      Strong Inhibitor of Tau Phosphorylation and beta-Amyloid Aggregation.
AB  - Alzheimer's disease (AD) has become one of the most serious societal problems
      globally, with no effective treatments. Parenchymal accumulation of amyloid beta
      (Abeta) plaques and the formation of neurofibrillary tangles are the hallmarks of
      AD. Their possible interactions and synergistic effects in AD have been gradually
      elucidated. The failure of many clinical trials suggests that it is difficult to
      treat AD with a focus on a single target. Instead, multiple targets may be an
      important direction for AD drug research. In this study, we used protoporphyrin
      IX (PX)-modified oxidized mesoporous carbon nanospheres (OMCN)
      (PX@OMCN@PEG(OP)@RVGs) as a novel AD multifunctional nanodrug having multiple
      targets. The nanodrug efficiently inhibits tau phosphorylation. In addition, the
      use of PX with focused ultrasound triggered the production of reactive oxygen
      species that significantly inhibited Abeta aggregation. Both approaches notably
      increased the cognitive level of APP/PS1 transgenic (Tg) mice and ultimately
      achieved dual-target inhibition of AD. Furthermore, the safe and effective
      delivery of PX across the blood-brain barrier (BBB) due to modification of the
      RVG peptide was demonstrated in vivo and in vitro. The favorable photothermal
      effect of the nanoparticles improved the BBB permeability of PX@OP@RVGs under
      near-infrared irradiation. The results demonstrated that the novel PX@OP@RVG
      multifunctional nanomedicine has a dual-target treatment capability for AD and
      can traverse the BBB, indicating the potential for the effective treatment of AD.

PMID- 30192127
TI  - Ultrasmall Grained Pd Nanopattern H2 Sensor.
AB  - Precise control of the size and interfaces of Pd grains is very important for
      designing a high-performance H2 sensing channel because the transition of the Pd
      phase from alpha to beta occurs through units of single grains. However,
      unfortunately, the grain controllability of previous approaches has been limited
      to grains exceeding 10 nm in size and simple macroscopic channel structures have
      only shown monotonic response behavior for a wide concentration range of H2. In
      this work, for the first time, we found that Pd channels that are precisely grain
      controlled show very different H2 sensing behavior. They display dual-switching
      response behavior with simultaneous variation of the positive and negative
      response direction within single sensor. The Pd nanopattern channel having
      smallest grain size/interface among previous works could be fabricated via unique
      lithographic approaches involving low-energy plasma (Ar+) bombardment. The
      ultrasmall grain size (5 nm) and narrow interface gap (<2 nm) controlled by Ar+
      plasma bombardment enabled both the hydrogen-induced lattice expansion (HILE)
      (Delta RH2 < 0) and surface electron scattering (Delta RH2 > 0) mechanisms to be
      simultaneously applied to the single Pd channel, thereby inducing dual-switching
      response according to the H2 concentration range. In addition, the unique high
      aspect-ratio high-resolution morphological characteristics made it possible to
      achieve highly sensitive H2 detecting performance (limit of detection: 2.5 ppm)
      without any hysteresis and irreversible performance degradation. These noteworthy
      new insights are attributed to high-resolution control of the grain size and the
      interfaces with the Pd nanostructure channel.

PMID- 30192128
TI  - MicroPlate Sialyltransferase Assay: A Rapid and Sensitive Assay Based on an
      Unnatural Sialic Acid Donor and Bioorthogonal Chemistry.
AB  - Mammalian sialyltransferases transfer sialic acids onto glycoproteins and
      glycolipids within the Golgi apparatus. Despite their key role in glycosylation,
      the study of their enzymatic activities is limited by the lack of appropriate
      tools. Herein, we developed a quick and sensitive sialyltransferase microplate
      assay based on the use of the unnatural CMP-SiaNAl donor substrate. In this
      assay, an appropriate acceptor glycoprotein is coated on the bottom of 96-well
      plate and the sialyltransferase activity is assessed using CMP-SiaNAl. The alkyne
      tag of SiaNAl enables subsequent covalent ligation of an azido-biotin probe via
      CuAAC and an antibiotin-HRP conjugated antibody is then used to quantify the
      amount of transferred SiaNAl by a colorimetric titration. With this test, we
      evaluated the kinetic characteristics and substrate preferences of two human
      sialyltransferases, ST6Gal I and ST3Gal I toward a panel of asialoglycoprotein
      acceptors, and identified cations that display a sialyltransferase inhibitory
      effect.

PMID- 30192129
TI  - Using High-Resolution Mass Spectrometry to Identify Organic Contaminants Linked
      to Urban Stormwater Mortality Syndrome in Coho Salmon.
AB  - Urban stormwater is a major threat to ecological health, causing a range of
      adverse, mostly sublethal effects. In western North America, urban runoff is
      acutely lethal to adult coho salmon ( Oncorhynchus kisutch) that spawn each fall
      in freshwater creeks. Although the mortality syndrome is correlated to
      urbanization and attributed to road runoff contaminant(s), the causal agent(s)
      remain unknown. We applied high-resolution mass spectrometry to isolate a coho
      mortality chemical signature: a list of nontarget and identified features that co
      occurred in waters lethal to coho spawners (road runoff from controlled exposures
      and urban receiving waters from two field observations of symptomatic coho).
      Hierarchical cluster analysis indicated that tire wear particle (TWP) leachates
      were most chemically similar to the waters with observed toxicity, relative to
      other vehicle-derived sources. Prominent road runoff contaminants in the
      signature included two groups of nitrogen-containing compounds derived from TWP,
      polyethylene glycols, octylphenol ethoxylates, and polypropylene glycols. A
      (methoxymethyl)melamine compound family, previously unreported in North America,
      was detected in road runoff and urban creeks at concentrations up to ~9 and ~0.3
      MUg/L, respectively. The results indicate TWPs are an under-appreciated
      contaminant source in urban watersheds and should be prioritized for fate and
      toxicity assessment.

PMID- 30192130
TI  - New Chemistry for New Material: Highly Dense Mesoporous Carbon Electrode for
      Supercapacitors with High Areal Capacitance.
AB  - The discovery of new chemical reactions plays an important role in new material
      synthesis. For electric double-layer capacitors, a high packing density and a
      large surface area are required, but contradiction for current porous carbon
      electrodes. This causes a critical trade-off issue among gravimetric, areal, and
      volumetric capacitances. Herein, a new chemistry was found to synthesize a new
      type of carbon material, namely, a new reaction between CO and Li directly
      produces three-dimensional dense mesoporous carbon (DMPC). Its high packing
      density of 1.94 g/cm3 is much larger than those (0.05-0.7 g/cm3) of other porous
      carbon materials. Consequently, the aqueous electric double-layer capacitors with
      DMPC electrodes, which have 11.5 mg/cm2 mass loading, can reach high areal
      capacitance (2.15 F/cm2 at 1 A/g). It also exhibited large volumetric and
      gravimetric capacitances (220.5 F/cm3 and 205.2 F/g) without sacrificing areal
      capacitance. Furthermore, after 5000 charge/discharge cycles, capacitance
      retention is as large as 98.4%, indicating a high stability of the electrode.
      Therefore, DMPC is an excellent material for the electrodes of practical electric
      double-layer capacitors.

PMID- 30192131
TI  - High-Vacuum Particulate-Free Deposition of Wafer-Scale Mono-, Bi-, and Trilayer
      Molybdenum Disulfide with Superior Transport Properties.
AB  - Wafer-scale MoS2 growth at arbitrary integer layer number is demonstrated by a
      technique based on the decomposition of carbon disulfide on a hot molybdenum
      filament, which yields volatile MoS x precursors that precipitate onto a heated
      wafer substrate. Colorimetric control of the growth process allows precise
      targeting of any integer layer number. The method is inherently free of
      particulate contamination, uses inexpensive reactants without the pyrophoricity
      common to metal-organic precursors, and does not rely on particular gas-flow
      profiles. Raman mapping and photoluminescence mapping, as well as imaging by
      electron microscopy, confirm the layer homogeneity and crystalline quality of the
      resultant material. Electrical characterization revealed microampere output
      current, outstanding device-to-device consistency, and exceptionally low noise
      level unparalleled even by the exfoliated material, while other transport
      properties are obscured by high-resistance contacts typical to MoS2 devices.

PMID- 30192132
TI  - Hypoxia-Activated Anticancer Prodrug for Bioimaging, Tracking Drug Release, and
      Anticancer Application.
AB  - A novel anticancer theranostic prodrug, FDU-DB-NO2, specifically activated by
      hypoxia for selective two-photon imaging hypoxia status, real-time tracking drug
      release, and solid tumor therapy was designed. The devised prodrug consists of an
      anticancer drug floxuridine (FDU), a fluorescence dye precursor 4'-(diethylamino)
      1,1'-biphenyl-2-carboxylate (DB), and a hypoxic trigger 4-nitrobenzyl group. In
      normal cells, FDU-DB-NO2 is "locked". Whereas in tumor cells, the prodrug is
      "unlocked" by hypoxia and results in fluorescent dye 7-(diethylamino)coumarin
      (CM) generation along with FDU release. The amounts and rates of CM formation and
      FDU release were controlled by hypoxic status and increased with the decreasing
      of the O2 concentration. The hypoxic status, distribution of oxygen, and amount
      of FDU release in tumor cells, spheroids, and tumor tissue could be visualized by
      fluorescence. FDU-DB-NO2 showed high cytotoxicity against hypoxic MCF-7 and MCG
      803 cell lines and no cytotoxicity against normoxic BRL-3A cells and exhibited
      effective inhibition on tumor growth of MCF-7-cell-inoculated xenograft nude
      mice. This strategy may provide a promising platform for selective two-photon
      imaging hypoxia status, real-time tracking drug release, and personalized solid
      tumor treatment.

PMID- 30192133
TI  - Larch Tree Rings as a Tool for Reconstructing 20th Century Central European
      Atmospheric Mercury Trends.
AB  - We propose the tree rings of European Larch ( Larix decidua) as a widely
      available and reliable geochemical archive of local and regional changes in
      atmospheric mercury (Hg). Mean Hg concentrations in larch tree rings from 8
      background sites across the Czech Republic ranged from 2.2 to 4.8 MUg kg-1; the
      maximum concentrations occurred in the period 1951-1970. At 3 sites impacted by
      Hg-emission sources [gold amalgamation processing, caustic soda production, and
      lead (Pb) ore smelting] mean larch tree ring Hg concentrations were significantly
      elevated relative to background sites. Changes in larch tree ring Hg
      concentrations were temporally coherent with known activities at the sites that
      would alter Hg emissions; the nearly simultaneous response in tree rings
      indicated little or no translocation of Hg within the larch bole. Based on the
      present-day atmospheric Hg concentration of 1.63 ng m-3 at the intensively
      monitored Czech Global Mercury Observation System site and the most recent mean
      tree ring Hg concentration of 2.8 MUg kg-1 in co-located larch trees, we
      developed a simple distribution model of Hg between the atmosphere and larch tree
      rings. We applied the model using observed changes of Hg in larch tree rings from
      the countrywide background sites to reconstruct past atmospheric Hg
      concentrations in central Europe. Modeled Hg concentrations were in agreement
      with annual means from the European Monitoring and Evaluation Programme
      observatories.

PMID- 30192134
TI  - Surface-Engineered Paper Hanging Drop Chip for 3D Spheroid Culture and Analysis.
AB  - Protein corona coated onto the hydrophilic cellulose fiber turns into hydrophobic
      upon UV irradiation without hindering the porosity of the paper while
      simultaneously reducing nonspecific adsorption. Taking advantage of the
      biofouling-resistant, hydrophobic, and fluid transport through property, we
      demonstrated hanging drop three-dimensional (3D) spheroid culture and in-site
      analysis, including drug testing, time-dependent detection of secreted protein,
      and fluorescence staining without disturbing the spheroids. This single hanging
      drop system can also be extended to a networked hanging drop chip to mimic in
      vivo microphysiology by combining with wax-patterned microfluidic channels, where
      well-to-well interaction can be accurately controlled in a passive manner. As a
      proof of concept, the effects of a concentration gradient of nutrient and
      variable dosage of anticancer drugs were studied in the 3D spheroids cultured on
      paper. The experimental results suggested that a complex network device could be
      fabricated on a large scale on demand at a minimal cost for 3D spheroid culture.
      Our method demonstrates a future possibility for paper as a low cost, high
      throughput 3D spheroid-based "body-on-a-chip" platform material.

PMID- 30192136
TI  - Electrically Conductive Polydopamine-Polypyrrole as High Performance Biomaterials
      for Cell Stimulation in Vitro and Electrical Signal Recording in Vivo.
AB  - Conductive polymers (CPs) such as polypyrrole (PPY) are emerging biomaterials for
      use as scaffolds and bioelectrodes which interact with biological systems
      electrically. Still, more electrically conductive and biologically interactive
      CPs are required to develop high performance biomaterials and medical devices. In
      this study, in situ electrochemical copolymerization of polydopamine (PDA) and
      PPY were performed for electrode modification. Their material and biological
      properties were characterized using multiple techniques. The electrical
      properties of electrodes coated with PDA/PPY were superior to electrodes coated
      with PPY alone. The growth and differentiation of C2C12 myoblasts and PC12
      neuronal cells on PDA/PPY was enhanced compared to PPY. Electrical stimulation of
      PC12 cells on PDA/PPY further promoted neuritogenesis. In vivo electromyography
      signal measurements demonstrated more sensitive signals from tibia muscles when
      using PDA/PPY-coated electrodes than bare or PPY-coated electrodes, revealing
      PDA/PPY to be a high-performance biomaterial with potential for various
      biomedical applications.

PMID- 30192137
TI  - Unraveling the Operational Mechanisms of Chemically Propelled Motors with
      Micropumps.
AB  - The development of effective autonomous micro- and nanomotors relies on
      controlling fluid motion at interfaces. One of the main challenges in the
      engineering of such artificial machines is the quest for efficient mechanisms to
      power them without using external driving forces. In the past decade, there has
      been an important increase of man-made micro- and nanomotors fueled by self
      generated physicochemical gradients. Impressive proofs of concept of multitasking
      machines have been reported demonstrating their capabilities for a plethora of
      applications. While the progress toward applications is promising, there are
      still open questions on fundamental physicochemical aspects behind the mechanical
      actuation, which require more experimental and theoretical efforts. These efforts
      are not merely academic but will open the door for an efficient and practical
      implementation of such promising devices. In this Account, we focus on chemically
      driven motors whose motion is the result of a complex interplay of chemical
      reactions and (electro)hydrodynamic phenomena. A reliable study of these
      processes is rather difficult with mobile objects like swimming motors. However,
      pumps, which are the immobilized motor counterparts, emerge as simple
      manufacturing and well-defined platforms for a better experimental probing of the
      mechanisms and key parameters controlling the actuation. Here we review some
      recent studies using a new methodology that has turned out to be very helpful to
      characterize micropump chemomechanics. The aim was to identify the redox role of
      the motor components, to map the chemical reaction, and to quantify the relevant
      electrokinetic parameters (e.g., electric field and fluid flow). This was
      achieved by monitoring the velocity of differently charged tracers and by
      fluorescence imaging of the chemical species involved in the chemical reaction,
      for example, proton gradients. We applied these techniques to different systems
      of interest. First, we probed bimetallic pumps as counterparts of the pioneering
      bimetallic swimmers. We corroborated that fluid motion was due to a self
      generated electro-osmotic mechanism driven by the redox decomposition of H2O2. In
      addition, we analyzed by simulations the key parameters that yield an optimized
      operation. Moreover, we accomplished a better assessment of the importance of
      surface chemistry on the metal electrochemical response, highlighting its
      relevance in controlling the redox role of the metals and motion direction.
      Second, we focused on metallic and semiconductor micropumps to analyze light
      controlled motion mechanisms through photoelectrochemical decomposition of fuels.
      These pumps were driven by visible light and could operate using just water as
      fuel. In these systems, we found a very interesting competition between two
      different mechanisms for fluid propulsion, namely, light-activated electro
      osmosis and light-insensitive diffusio-osmosis, stemming from different chemical
      pathways in the fuel decomposition. In this case, surface roughness becomes a
      pivotal parameter to enhance or depress one mechanism over the other. These
      examples demonstrate that pumps are practical platforms to explore operating
      mechanisms and to quantify their performance. Additionally, they are suitable
      systems to test novel fuels or motor materials. This knowledge is extensible to
      swimmers providing not only fundamental understanding of their locomotion
      mechanisms but also useful clues for their design and optimization.

PMID- 30192139
TI  - Differential Proteome Analysis of Chikungunya Virus and Dengue Virus Coinfection
      in Aedes Mosquitoes.
AB  - Chikungunya virus (CHIKV) and dengue virus (DENV) are important arboviruses
      transmitted by Aedes mosquitoes. These viruses are known to coexist within the
      same vector and coinfect the same host. Although information is available on the
      mechanism of replication of CHIKV and DENV when present independently in a
      vector, reports are lacking on the dynamics of virus-vector interactions when
      these viruses coexist in a mosquito. The current study attempts to understand the
      perturbations in the proteome of Aedes mosquitoes when infected with CHIKV and
      DENV either independently or together. Global proteome profiling of chikungunya
      and dengue mono- and coinfection revealed 28 proteins to be significantly
      regulated. Validation of the transcripts of these proteins using qRT-PCR
      indicated differences in the expression patterns between transcript profiling and
      quantitative proteome analyses. Pathway analysis of the 28 differentially
      regulated proteins revealed 11 significant pathways, which include oxidative
      phosphorylation, carbon metabolism, and glycolysis/gluconeogenesis.

PMID- 30192138
TI  - Ultralight MXene-Coated, Interconnected SiCnws Three-Dimensional Lamellar Foams
      for Efficient Microwave Absorption in the X-Band.
AB  - Two-dimensional (2D) few-layered Ti3C2T X MXene (f-Ti3C2T X) has been proved to
      be one of the most promising electromagnetic interference (EMI) materials, but
      its electromagnetic (EM) absorption properties and loss mechanism have not been
      studied so far. Herein, for the first time, ordered lamellar f-Ti3C2T X/SiCnws
      hybrid foams with ultralow density are synthesized by a combination of self
      assembly and bidirectional freezing processes. The freestanding foams exhibit
      excellent EM absorption properties superior to most of the current foam-based
      counterparts. The effective absorption bandwidth is always able to cover the
      whole X-band, when the sample thicknesses of f-Ti3C2T X/SiCnws hybrid foams
      distribute in any value between 3.5 and 3.8 mm, and the minimum reflection
      coefficient reaches -55.7 dB at an ultralow density of only about 0.029 g.cm-3.
      The fundamental mechanism associated with optimized impedance matching, enhanced
      polarization loss, and conductive loss is discussed in detail. Our results
      evidence that 2D flexible f-Ti3C2T X MXene has great potential in EM absorption
      field like graphene.

PMID- 30192141
TI  - Effects of Positive and Negative Ionization on Prototropy in Pyrimidine Bases: An
      Unusual Case of Isocytosine.
AB  - Intramolecular proton-transfers (prototropic conversions) have been studied for
      the guanine building block isocytosine (iC), and effects of positive ionization,
      called one-electron oxidation (iC - e -> iC+*), and negative ionization, called
      one-electron reduction (iC + e -> iC-*), on tautomeric conversions when
      proceeding from neutral to ionized isocytosine have been discussed. Although
      radical cations and radical anions are very short-lived species, the ionization
      effects could be investigated by quantum-chemical methods. Such kind of studies
      gives some information about the labile protons and the most basic positions in
      the neutral and radical forms of the tautomeric system. For investigations, the
      complete isomeric mixture of isocytosine has been considered and calculations
      performed in two extreme environments, apolar {DFT(B3LYP)/6-311+G(d,p)} and polar
      {PCM(water)//DFT(B3LYP)/6-311+G(d,p)}. For selected isomers, the G4 theory has
      also been applied. There are no good relations for energetic parameters of
      neutral and ionized forms. Ionization energies depend on localization of labile
      protons. Tautomeric equilibria for neutral and ionized isocytosine, favored sites
      of protonation and deprotonation, and favored structures of protonated and
      deprotonated forms strongly depend on environment. Acidity of iC+* is close to
      that of the iC conjugate acid, and basicity of iC-* is close to that of the iC
      conjugate base. This increase of acid-base properties of charged radicals
      explains the proton-transfer in ionized pairs of nucleobases. When compared to
      other pyrimidine bases such as uracil (U) and cytosine (C), which exhibit
      analogous tautomeric equilibria between nine prototropic tautomers as
      isocytosine, the tautomeric preferences for iC, iC+*, iC-*, U, U+*, U-*, C, C+*,
      and C-* are completely different. The differences suggest that acid-base
      properties of functional groups, their stabilities, and ionization energies play
      a principal role in proton-transfers for pyrimidine bases and influence
      compositions of tautomeric mixtures.

PMID- 30192140
TI  - Concentrations and Distribution Patterns of Perfluoroalkyl Acids in Sewage Sludge
      and in Biowaste in Hesse, Germany.
AB  - A total of 201 sewage sludge and 45 biowaste samples were examined for 14
      different perfluoroalkyl acids (PFAA). For perfluorooctanesulfonic acid, maximum
      concentrations of 698 MUg/kg dry weight were measured in sewage sludge and for
      perfluorohexanesulfonic acid 29.0 MUg/kg dry weight were found in biowaste.
      Looking at the fingerprints of both these matrixes it can be see that long-chain
      PFAA make up 85.9% of the total concentration in sewage sludge whereas short
      chain PFAA only account for 14.1%. In contrast, the trend in biowaste is just the
      opposite, with 53.2% long-chain and 46.8% short-chain PFAA. These results lead to
      the conclusion that sewage sludge functions as a sink for long-chain PFAA, and
      the plants preferentially take up short-chain PFAA from the sludge/soil, as seen
      by the concentrations found in biowaste. It can be calculated that the total
      yearly amount of PFAA spread onto agricultural lands amount to 15.3 kg.

PMID- 30192142
TI  - Time-Resolved Protein Side-Chain Motions Unraveled by High-Resolution Relaxometry
      and Molecular Dynamics Simulations.
AB  - Motions of proteins are essential for the performance of their functions.
      Aliphatic protein side chains and their motions play critical roles in protein
      interactions: for recognition and binding of partner molecules at the surface or
      serving as an entropy reservoir within the hydrophobic core. Here, we present a
      new NMR method based on high-resolution relaxometry and high-field relaxation to
      determine quantitatively both motional amplitudes and time scales of methyl
      bearing side chains in the picosecond-to-nanosecond range. We detect a wide
      variety of motions in isoleucine side chains in the protein ubiquitin. We
      unambiguously identify slow motions in the low nanosecond range, which, in
      conjunction with molecular dynamics computer simulations, could be assigned to
      transitions between rotamers. Our approach provides unmatched detailed insight
      into the motions of aliphatic side chains in proteins and provides a better
      understanding of the nature and functional role of protein side-chain motions.

PMID- 30192143
TI  - Quantum Design for Ultrafast Probing of Molecular Chirality through Enantiomer
      Specific Coherent pi-Electron Angular Momentum.
AB  - Probing molecular chirality, right-handed or left-handed chiral molecules, is one
      of the central issues in chemistry and biochemistry. The conventional theory of
      optical activity measurements such as circular dichroism has been derived in the
      second-order processes involving electric and magnetic dipole moments, and the
      signals are very weak. We propose an efficient enantiomer-probing scenario for
      chiral aromatic ring molecules based on photoinduced coherent pi-electron
      rotations. In our model, the resultant laser-induced currents themselves produce
      a strong magnetic field. The principle for probing molecular chirality is a
      utilization of dynamic Stark effects of two electronic excited states. These
      electronic states subjected to strong nonresonant linearly polarized UV lasers
      become degenerate to create enantiomer-specific electronic angular momentum. A
      pair of enantiomers of phenylalanine was taken as an example. Enantiomer-specific
      coherent magnetic fluxes on the order of a few teslas can be generated in several
      tens of femtoseconds. The direct detection of strong coherent magnetic fluxes
      could be carried out by time-resolved magnetic force microscopy experiments. The
      results provide important implications for the measurement of effective probing
      of chiral aromatic molecules.

PMID- 30192144
TI  - Synthesis of Nonaromatic and Aromatic Dithia Benzisapphyrins.
AB  - A series of [24pi] dithia meta-benzisapphyrins and [22pi] dithia para
      benzisapphyrins were synthesized by 3 + 2 condensation of appropriate
      benzitripyrrane with bithiophene diol under mild acid catalyzed conditions. The
      dithia m-benzisapphyrins and dithia p-benzisapphyrins were thoroughly
      characterized by HR-MS, 1D and 2D NMR, absorption, and electrochemical
      techniques. Our studies showed that dithia m-benzisapphyrins are nonaromatic,
      whereas the dithia p-benzisapphyrins are aromatic in nature. Thus, we
      demonstrated here that the dithiabenzisapphyrins can be made aromatic by
      replacing the m-phenylene moiety of the benzisapphyrin macrocycle with a p
      phenylene unit. Furthermore, the studies also indicated that the aromaticity of
      the dithia p-benzisapphyrins was relatively more compared to the reported
      heterosapphyrins. The structural and spectral characteristics including
      aromaticity of the m-benzisapphyrins and p-benzisapphyrins were also discussed
      with the help of DFT, NICS, and TD-DFT studies.

PMID- 30192146
TI  - Correction to Food Bioactives and Their Effects on Obesity-Accelerated
      Inflammatory Bowel Disease.

PMID- 30192145
TI  - Direct N-H/ N-Me Aziridination of Unactivated Olefins Using O
      (Sulfonyl)hydroxylamines as Aminating Agents.
AB  - Unactivated aziridines are the core substructures in a plethora of bioactive
      natural products and serve as building blocks in organic synthesis. Despite this,
      very limited methods are available to access them directly from olefins, as most
      of the known methods are devoted to their activated counterparts. Herein, we have
      developed a highly efficient Rh(II)-catalyzed method for the direct preparation
      of unactivated aziridines from olefins using O-(sulfonyl)hydroxylamines as the
      aminating agent. The reactions proceed with a high stereospecificity.

PMID- 30192148
TI  - Microwave-Enhanced On-Water Amination of 2-Mercaptobenzoxazoles To Prepare 2
      Aminobenzoxazoles.
AB  - In this work, we developed a catalyst-free amination of 2-mercaptobenzoxazoles on
      water under microwave irradiation. The product, 2-aminobenzoxazoles, was
      successfully produced via direct amination with various amines in moderate to
      high yields. The formal synthesis of Suvorexant, a medication for the treatment
      of insomnia, was accomplished using a developed amination process. The reaction
      was completed in an hour at 100-150  degrees C in a microwave reactor without the
      use of external catalyst or additive. Key benefits of this process include an on
      water reaction, short reaction time, being scalable and catalyst-free, and use of
      2-mercaptobenzoxazoles as an inexpensive starting material having low
      environmental impact in its preparation.

PMID- 30192147
TI  - Spin-Orbit Interaction and Induced Superconductivity in a One-Dimensional Hole
      Gas.
AB  - Low dimensional semiconducting structures with strong spin-orbit interaction
      (SOI) and induced superconductivity attracted great interest in the search for
      topological superconductors. Both the strong SOI and hard superconducting gap are
      directly related to the topological protection of the predicted Majorana bound
      states. Here we explore the one-dimensional hole gas in germanium silicon (Ge-Si)
      core-shell nanowires (NWs) as a new material candidate for creating a topological
      superconductor. Fitting multiple Andreev reflection measurements shows that the
      NW has two transport channels only, underlining its one-dimensionality.
      Furthermore, we find anisotropy of the Lande g-factor that, combined with band
      structure calculations, provides us qualitative evidence for the direct Rashba
      SOI and a strong orbital effect of the magnetic field. Finally, a hard
      superconducting gap is found in the tunneling regime and the open regime, where
      we use the Kondo peak as a new tool to gauge the quality of the superconducting
      gap.

PMID- 30192149
TI  - Biosynthesis-Inspired Approach to Kujounin A2 Using a Stereoselective Tsuji-Trost
      Alkylation.
AB  - A new biosynthesis was proposed for the kujounins A1 and A2 beginning from
      ascorbic acid, which in turn inspired a synthetic approach to kujounin A2. The
      ring system was assembled in two steps using a stereoselective Tsuji-Trost
      reaction followed by ozonolysis. The chemically labile disulfide was introduced
      in several more steps. These results will make kujounin and its analogues
      available for further evaluation.

PMID- 30192150
TI  - Intramolecular Diels-Alder Reaction of a Silyl-Substituted Vinylimidazole en
      Route to the Fully Substituted Cyclopentane Core of Oroidin Dimers.
AB  - An intramolecular Diels-Alder reaction of a silyl-substituted vinylimidazole
      delivers a diastereomeric mixture of C4-silyl functionalized
      dihydrobenzimidazoles. Subsequent diastereoselective reduction and elaboration of
      the lactone gives rise to a polysubstituted tetrahydrobenzimidazole, which, upon
      oxidative rearrangement, affords a single spirofused imidazolone containing all
      of the relevant functionality for an approach to the oroidin dimers axinellamine,
      massadine, and palau'amine.

PMID- 30192151
TI  - Visible Light-Mediated Photocatalytic Metal-Free Cross-Coupling Reaction of
      Alkenyl Carboxylic Acids with Diarylphosphine Oxides Leading to beta
      Ketophosphine Oxides.
AB  - A new visible light-mediated photocatalytic decarboxylative oxyphosphorylation of
      cinnamic acids with diarylphosphine oxides is described. This reaction is
      performed under mild conditions to afford the corresponding beta-ketophosphine
      oxides.

PMID- 30192152
TI  - Synthesis of beta-Alkyl 2-Hydroxychalcones by Rhodium-Catalyzed Coupling of N
      Phenoxyacetamides and Nonterminal Propargyl Alcohols.
AB  - An efficient rhodium-catalyzed coupling of N-phenoxyacetamides and nonterminal
      propargyl alcohols has been developed. A series of beta-Alkyl 2-hydroxychalcones
      bearing diverse functional groups were obtained with excellent regio- and
      stereoselectivity, and the desired chalcones could then be converted to triazole
      and chromene smoothly.

PMID- 30192153
TI  - Cu-Catalyzed Enantioselective Atropisomer Synthesis via Thiolative Ring Opening
      of Five-Membered Cyclic Diaryliodoniums.
AB  - A Cu-catalyzed asymmetric thiolative ring opening reaction of five-membered
      diaryliodonium salts and potassium thioates for the synthesis of atropisomeric 2'
      iodo-[1,1'-biphenyl]-2-yl thioates was realized. The optimal catalytic system,
      Cu(CH3CN)4PF6/(Ph)-bis(oxazoline), showed the best performance with respect to
      both yields and stereocontrol. Finally, the utility of these products was briefly
      demonstrated by the synthesis of an axially chiral P,S-ligand.

PMID- 30192154
TI  - Visible-Light-Induced Intermolecular Dearomative Cyclization of 2-Bromo-1,3
      dicarbonyl Compounds and Alkynes: Synthesis of Spiro[4.5]deca-1,6,9-trien-8-ones.
AB  - A visible-light-induced photocatalytic intermolecular dearomative cyclization of
      2-bromo-1,3-dicarbonyl compounds and alkynes afforded biologically important
      spirocarbocycle structures in moderate to good yields via a 5-exo-dig radical
      cyclization under mild reaction conditions. A 5.0 mmol scale dearomatization
      reaction proceeded smoothly with 95% yield even when the catalyst loading was
      reduced to 0.1 mol %, suggesting that this method was suitable for large-scale
      synthesis.

PMID- 30192155
TI  - Costs associated with adverse events for systemic therapies in metastatic
      melanoma.
AB  - AIM: To determine the costs of adverse events (AEs) associated with current
      metastatic melanoma (MM) therapies. MATERIALS & METHODS: Two retrospective cohort
      studies were independently conducted using the PharMetrics and MarketScan
      databases. Included patients were aged >=18 years, and had >=1 MM diagnosis and
      >=1 claim for systemic therapy from 2004 to 2015. RESULTS: A total of 1654 and
      1329 patients were identified in PharMetrics and MarketScan, respectively. The
      corresponding adjusted 30-day incremental costs of AEs by category were highest
      for CNS/psychiatric (US$21,277 and $18,739), gastrointestinal ($18,534 and
      $15,648), respiratory ($17,338 and $17,064), cardiovascular ($16,083 and
      $15,430), hematological/lymphatic ($14,997 and $15,538) and metabolic/nutritional
      AEs ($12,340 and $17,251). CONCLUSION: The costs of AEs associated with systemic
      therapies for MM are substantial.

PMID- 30192157
TI  - M-bioscore: proposing a new statistical model for prognostic factors in
      metastatic breast cancer patients.
AB  - AIM: The current study aims to propose and internally validate 'M-bioscore',
      which is a model to help predict the outcomes of untreated metastatic breast
      cancer patients. METHODOLOGY: Surveillance, epidemiology and end results (SEER)
      database (2010-2013) was accessed. Patients were divided into two groups: a
      training set and a validation set. Through a Cox proportional model, multivariate
      analysis for potential prognostic factors was performed. M-bioscore was
      calculated for all patients. Survival analyses were conducted through Kaplan
      Meier analysis/log-rank testing. RESULTS: A total of 6655 metastatic breast
      cancer patients were analyzed. In the training set, the following factors were
      linked to better cancer-specific survival in multivariate analysis: estrogen
      receptor positivity, isolated distant nodal metastases, progesterone receptor
      positivity, lower nuclear grade and HER2 neu positivity (p < 0.01). Cancer
      specific survival was then assessed according to M-bioscore. Adjusted Cox
      regression cause-specific hazard (using breast cancer death as the event of
      interest) was evaluated in the validation cohort. Pairwise hazard ratio
      comparisons between different scores were significant (p < 0.05) except for the
      comparison between score 6 and 7. C-index for the validation cohort was 0.665
      (Standard error (SE): 0.010; 95% CI: 0.646- 0.685). CONCLUSION: M-bioscore can
      predict the outcomes of untreated metastatic breast cancer patients. Validation
      of external datasets is needed.

PMID- 30192156
TI  - The Diurnal and Nocturnal Effects of Pilocarpine on Intraocular Pressure in
      Patients Receiving Prostaglandin Analog Monotherapy.
AB  - PURPOSE: The purpose of the study was to determine the 24-h effects of
      pilocarpine 2% ophthalmic solution on intraocular pressure (IOP) and ocular
      perfusion pressure (OPP) when used in addition to prostaglandin analog (PGA)
      therapy. METHODS: Twenty-seven patients with ocular hypertension (OHTN) or open
      angle glaucoma who were receiving stable monotherapy with a PGA were admitted to
      an inpatient sleep laboratory for 24-h monitoring of IOP, blood pressure (BP),
      and heart rate over 2 separate visits. The first baseline visit was performed
      under PGA monotherapy only. During the second 24-h visit, pilocarpine 2% was
      administered four times daily in addition to their normal PGA dosing. For each
      study visit, measurements of all study metrics were performed every 2 h in the
      habitual position. OPP was calculated as 2/3[diastolic BP +1/3(systolic BP -
      diastolic BP)] - IOP. RESULTS: During the diurnal period, pilocarpine
      significantly reduced IOP from a baseline of 18.2 +/- 0.5 mmHg on PGA monotherapy
      to 17.1 +/- 0.4 mmHg, P < 0.01. Similarly, pilocarpine significantly lowered IOP
      during the nocturnal period from 21.1 +/- 0.7 to 20.0 +/- 0.6 mmHg, P < 0.01.
      Mean OPP was unchanged from baseline levels after the addition of pilocarpine in
      both the diurnal and nocturnal periods. Mean systolic BP was significantly
      reduced during the nocturnal period only (-3.16 +/- 1.5 mmHg, P = 0.03).
      CONCLUSIONS: In patients taking PGA monotherapy, the addition of pilocarpine can
      significantly lower IOP throughout the diurnal and nocturnal periods, but has no
      effect on OPP.

PMID- 30192158
TI  - Interferon Gamma Inhibits CXCL8-Induced Proliferation and Migration of Pancreatic
      Cancer BxPC-3 Cell Line via a RhoGDI2/Rac1/NF-kappaB Signaling Pathway.
AB  - Interferon gamma (IFN-gamma) is a dimeric soluble cytokine and the only type II
      interferon. Accumulated evidence suggests that IFN-gamma inhibits tumor
      progression. This study investigated the effects of IFN-gamma on the
      proliferation and migration of pancreatic cancer (PC) cells and the underlying
      mechanism. IFN-gamma treatment decreased the expression and secretion of CXCL8 in
      BxPC-3 PC cells, suppressed the proliferation and migration of these cells, and
      enhanced their apoptosis, as determined by increased levels of cleaved Caspase-8
      and Bax together with reduced expression of Bcl-2. These effects were abolished
      by overexpression of CXCL8. Moreover, IFN-gamma treatment downregulated RhoGDI2
      expression. Depletion of RhoGDI2 and Rac1 by using small interfering RNAs and
      inhibition of NF-kappaB by BMS-345541 (an IkappaB kinase [IKK] inhibitor)
      suppressed expression of CXCL8. Our results indicate that IFN-gamma inhibits the
      proliferation and migration of PC cells by suppressing CXCL8 expression via a
      RhoGDI2/Rac1/NF-kappaB signaling pathway.

PMID- 30192159
TI  - Some issues for the evaluation of noninferiority trials.
AB  - Although published noninferiority trials (NITs) generally conclude that the
      experimental intervention being studied is noninferior compared with standard
      therapy or active control, NIT quality is often not satisfactory. We have
      proposed 14 questions to assist in evaluating the clinical evidence of the
      experimental versus standard therapy. The aim of these questions is to critically
      appraise NITs and support proper interpretation of study results. Readers should
      not only consider whether the confidence interval of the primary effect measure
      falls within the prespecified noninferiority margin (thus concluding
      noninferiority), but also assess the similarities between primary and secondary
      outcomes for the experimental and standard therapy. To conclude noninferiority
      conceptually is to synthesize evidence from both the current NIT comparing
      experimental therapy with standard therapy and historical data comparing standard
      therapy with placebo control. Therefore, readers should use external data sources
      (e.g., historical data) to validate the study design (e.g., selection of standard
      therapy, effect measure and the noninferiority margin), and assess the
      uncertainty of findings due to differences between the observed and expected
      incidence rates, follow-up time, effects of adjuvant therapy and the secondary
      outcomes of therapies. Following an explanation of the 14 questions, we then
      apply the questions to a NIT on intraoperative radiation therapy for early stage
      breast cancer, as an example.

PMID- 30192160
TI  - Atmospheric Dust, Early Cases, and Localized Meningitis Epidemics in the African
      Meningitis Belt: An Analysis Using High Spatial Resolution Data.
AB  - BACKGROUND: Bacterial meningitis causes a high burden of disease in the African
      meningitis belt, with regular seasonal hyperendemicity and sporadic short, but
      intense, localized epidemics during the late dry season occurring at a small
      spatial scale [i.e., below the district level, in individual health centers
      (HCs)]. In addition, epidemic waves with larger geographic extent occur every 7
      10 y. Although atmospheric dust load is thought to be an essential factor for
      hyperendemicity, its role for localized epidemics remains hypothetic. OBJECTIVES:
      Our goal was to evaluate the association of localized meningitis epidemics in HC
      catchment areas with the dust load and the occurrence of cases in the same
      population early in the dry season. METHODS: We compiled weekly reported cases of
      suspected bacterial meningitis at the HC resolution for 14 districts of Burkina
      Faso for the period 2004-2014. Using logistic regression, we evaluated the
      association of epidemic HC-weeks with atmospheric dust [approximated by the
      aerosol optical thickness (AOT) satellite product] and with the observation of
      early meningitis cases during October-December. RESULTS: Although AOT was
      strongly associated with epidemic HC-weeks in crude analyses across all HC-weeks
      during the meningitis season [odds ratio (OR) [Formula: see text]; 95% CI: 4.90,
      9.50], the association was no longer apparent when controlling for calendar week
      (OR [Formula: see text]; 95% CI: 0.60, 1.50). The number of early meningitis
      cases reported during October-December was associated with epidemic HC-weeks in
      the same HC catchment area during January-May of the following year (OR for each
      additional early case [Formula: see text]; 95% CI: 1.06, 1.21). CONCLUSIONS:
      Spatial variations of atmospheric dust load do not seem to be a factor in the
      occurrence of localized meningitis epidemics, and the factor triggering them
      remains to be identified. The pathophysiological mechanism linking early cases to
      localized epidemics is not understood, but their occurrence and number of early
      cases could be an indicator for epidemic risk. https://doi.org/10.1289/EHP2752.

PMID- 30192161
TI  - Evaluation and Optimization of Pharmacokinetic Models for in Vitro to in Vivo
      Extrapolation of Estrogenic Activity for Environmental Chemicals.
AB  - BACKGROUND: To effectively incorporate in vitro data into regulatory use,
      confidence must be established in the quantitative extrapolation of in vitro
      activity to relevant end points in animals or humans. OBJECTIVE: Our goal was to
      evaluate and optimize in vitro to in vivo extrapolation (IVIVE) approaches using
      in vitro estrogen receptor (ER) activity to predict estrogenic effects measured
      in rodent uterotrophic studies. METHODS: We evaluated three pharmacokinetic (PK)
      models with varying complexities to extrapolate in vitro to in vivo dosimetry for
      a group of 29 ER agonists, using data from validated in vitro [U.S. Environmental
      Protection Agency (U.S. EPA) ToxCastTM ER model] and in vivo (uterotrophic)
      methods. In vitro activity values were adjusted using mass-balance equations to
      estimate intracellular exposure via an enrichment factor (EF), and steady-state
      model calculations were adjusted using fraction of unbound chemical in the plasma
      ([Formula: see text]) to approximate bioavailability. Accuracy of each model
      adjustment combination was assessed by comparing model predictions with lowest
      effect levels (LELs) from guideline uterotrophic studies. RESULTS: We found
      little difference in model predictive performance based on complexity or route
      specific modifications. Simple adjustments, applied to account for in vitro
      intracellular exposure (EF) or chemical bioavailability ([Formula: see text]),
      resulted in significant improvements in the predictive performance of all models.
      CONCLUSION: Computational IVIVE approaches accurately estimate chemical exposure
      levels that elicit positive responses in the rodent uterotrophic bioassay. The
      simplest model had the best overall performance for predicting both oral (PPK_EF)
      and injection (PPK_[Formula: see text]) LELs from guideline uterotrophic studies,
      is freely available, and can be parameterized entirely using freely available in
      silico tools. https://doi.org/10.1289/EHP1655.

PMID- 30192163
TI  - Radiation Therapy for Treatment of Adolescent and Young Adult Hodgkin Lymphoma
      and Risk for Cardiovascular Disease and Cancer.
AB  - PURPOSE: To estimate the risk for hospitalizations among survivors of Hodgkin
      lymphoma diagnosed in adolescence or young adulthood according to exposure to
      treatment with radiation therapy. METHODS: Through the files of the Danish Cancer
      Registry, we identified 1684 five-year survivors of Hodgkin lymphoma, diagnosed
      at age 15-39 years during the period 1943-2004, and for whom information on
      radiation therapy was available in the Cancer Registry. Population-based
      comparisons were identified through the Danish Civil Registration System and
      matched to the survivors on year of birth and sex. Survivors of Hodgkin lymphoma
      and comparisons were linked to the Danish National Patient Register for
      information on hospitalizations. Standardized hospitalization rate ratios (RR)
      and absolute excess rates (AERs) were estimated for total number of
      hospitalizations and for hospitalizations for cardiovascular disease, cancer and
      several other disease groups. RESULTS: Overall, survivors of Hodgkin lymphoma who
      received radiation therapy had higher risk (RR 2.0) and AER (AER 588) of
      hospitalization than survivors not treated with radiation therapy (RR 1.8; AER
      399). Especially, the risk for cardiovascular disease and cancer was high among
      survivors who received radiation therapy (RR 2.8 and 3.6) compared with survivors
      who did not receive this type of treatment (RR 2.2 and 2.3). CONCLUSION:
      Survivors of adolescent and young adult Hodgkin lymphoma treated with radiation
      therapy had a higher risk of diseases requiring hospitalization than survivors
      not treated with radiation therapy. Irrespective of the type of treatment
      received, initiatives that prevent and minimize hospital-requiring late effects
      in survivors of Hodgkin lymphoma are needed.

PMID- 30192165
TI  - SATB2 and Hep Par 1 Immunohistochemistry Is Helpful in Distinguishing Between
      Inflamed and Architecturally Altered Ileal Pouch and Rectal Cuff Mucosa.
AB  - The management of patients with ulcerative colitis after proctocolectomy with
      ileal pouch-anal anastomosis includes independent histological assessments of
      inflammation in the ileal pouch and the rectal cuff. However, the distinction
      between pouchitis and cuffitis can be impeded both endoscopically and
      histologically by the combined effects of inflammation and regeneration. We
      investigated the use of 2 markers, hepatocyte paraffin 1 (Hep) and SATB2 (special
      AT-rich sequence-binding protein 2), which are expressed immunohistochemically in
      the small and large bowel epithelium, respectively, as ancillary methods to deal
      with this problem. Immunohistochemical staining was performed retrospectively on
      20 consecutive pairs of post-ileal pouch-anal anastomosis biopsies with varying
      degrees of histological inflammation and architectural distortion, which had each
      been designated as "ileal pouch" or "rectal cuff" by the referring endoscopists.
      Expression was graded as focal (10% to 74% stained cells) or diffuse (75% to
      100%). Among the ileal pouch biopsies, 20 (100%) expressed Hep either diffusely
      (75%) or focally (25%), whereas SATB2 staining was either negative in 15 (75%) or
      focal in 5 (25%), the latter group all expressing Hep diffusely. Among the rectal
      cuff biopsies, 14 expressed SATB2 diffusely. Of these, Hep was either negative in
      11 (79%) or focally positive in 3 (21%), the latter group all expressing SATB2
      diffusely. Six ostensibly rectal cuff biopsies (30%) expressed Hep diffusely and
      were negative for SATB2, suggesting endoscopic misidentification. None of the 40
      biopsies expressed both markers diffusely. We conclude that in doubtful cases,
      diffuse expression of either Hep or SATB2 can be helpful in discriminating
      between ileal pouch and rectal cuff mucosa, respectively.

PMID- 30192164
TI  - Chicken Liver-Associated Outbreaks of Campylobacteriosis and Salmonellosis,
      United States, 2000-2016: Identifying Opportunities for Prevention.
AB  - Chicken liver has been implicated in several reported U.S. illness outbreaks,
      probably caused by inadequate cooking and pathogen contamination. To identify
      commonalities among these outbreaks that could represent targets for prevention,
      we describe chicken liver-associated U.S. outbreaks during 2000-2016 reported to
      the Food Safety and Inspection Service, to the Centers for Disease Control and
      Prevention, and in published literature. We identified 28 outbreaks (23 [82.1%]
      were campylobacteriosis only, 3 [10.7%] were salmonellosis only, and 2 [7.1%]
      were caused by both pathogens), with 18 (64.3%) occurring during 2014-2016.
      Common outbreak features included blended chicken liver dishes (e.g., pate; 24
      [85.7%]), inadequate cooking (26 [92.8%]), and preparation in foodservice
      settings (e.g., sit-down restaurants; 25 [89.3%]). The increasing frequency of
      reported outbreaks highlights chicken liver as an important food safety problem.
      Public health partners should collaborate on prevention measures, including
      education on proper foodservice preparation of blended chicken liver dishes.

PMID- 30192166
TI  - Meropenem/colistin versus meropenem/ampicillin-sulbactam in the treatment of
      carbapenem-resistant pneumonia.
AB  - AIM: Efficacy of colistin and ampicillin-sulbactam have not been compared in
      treatment of ventilator-associated pneumonia due to A. baumannii. Efficacy of
      colistin and ampicillin-sulbactam in combination with meropenem were compared in
      treatment of ventilator-associated pneumonia due to carbapenem-resistant A.
      baumannii. METHOD: 47 patients with ventilator-associated pneumonia due to
      carbapenem-resistant A. baumannii were randomized to receive meropenem/colistin
      or meropenem/ampicillin-sulbactam for 14 days. Clinical and microbiological
      responses and 28-day mortality were considered as outcomes. RESULTS: Clinical
      response (75 vs 69.6%; p = 0.75) and microbial eradication (87.50 vs 91.3%; p =
      0.59) were comparable between meropenem/colistin and meropenem/ampicillin
      sulbactam groups, respectively. CONCLUSION: In this study, clinical and
      microbiological response were comparable between the meropenem/colistin and
      meropenem/ampicillin-sulbactam groups.

PMID- 30192167
TI  - Pancreatic cancer: let us focus on cachexia, not just sarcopenia!

PMID- 30192168
TI  - The Oncologic Outcomes of Inferior Mesenteric Artery-Preserving Laparoscopic
      Lymph Node Dissection for Upper-Rectal or Sigmoid Colon Cancer.
AB  - BACKGROUND: The standard procedure of lymph node (LN) dissection for rectal or
      sigmoid colon cancer remains controversial. Many laparoscopic surgeons cut the
      inferior mesenteric artery (IMA) at the root; however, this may cause bowel
      ischemia around the site of anastomosis. We performed D3 or D2 LN dissection with
      the preservation of the IMA. The aim of this study was to evaluate the oncologic
      outcomes of IMA-preserving LN dissection. PATIENTS AND METHODS: We
      retrospectively analyzed 142 consecutive patients with upper-rectal or sigmoid
      colon cancer who underwent laparoscopic LN dissection with the preservation of
      the IMA. The number of LNs dissected and the overall and disease-free survival
      rates were retrospectively evaluated. RESULTS: Laparoscopic D3 (n = 92) or D2 (n
      = 50) LN dissection were performed with the preservation of the IMA. The left
      colic artery was preserved in all cases, the superior rectal artery was also
      preserved in 30 cases. The mean number of LNs dissected was 19.6 in the D3 group
      and 12.9 in the D2 group. The median operative time was 230 minutes, and the
      median volume of blood loss was 17 mL. There was no treatment-related mortality.
      The estimated 5-year disease-free survival rates of the stage I, II, and III
      patients were 93%, 83%, and 74%, respectively. No patients developed LN
      recurrence. CONCLUSIONS: Laparoscopic surgery with IMA-preserving LN dissection
      is an oncologically acceptable treatment strategy in patients with upper-rectal
      or sigmoid colon cancer.

PMID- 30192169
TI  - Comparison of Polymeric Clips and Endoscopic Staplers for Laparoscopic
      Appendectomy.
AB  - INTRODUCTION: Appendectomy is the most common pediatric surgical procedure. To
      decrease the cost and environmental impact of single incision pediatric
      endosurgery (SIPES) appendectomy, we switched from using endoscopic staplers to
      polymeric clips placed with nondisposable laparoscopic appliers. The aim of this
      study was to compare the resulting reduction in cost and amount of waste
      generated per case, as well as to compare the perioperative variables and
      outcomes in patients in whom clips were used, with those of historical patients
      in whom staplers were used. MATERIALS AND METHODS: Retrospective chart review of
      SIPES appendectomies was performed and patients in whom clips were used were
      compared with patients in whom staplers were used. Demographic, operative, and
      clinical data were collected. t-Test, Mann-Whitney test, and chi squared test
      were used to analyze the data as appropriate. The cost to the hospital of the
      clips and staplers was compared. The disposable waste generated from clips and
      the staplers was weighed. RESULTS: A total of 246 patients were included: 111 in
      stapler group and 135 in clip group. There were no statistically significant
      differences between the groups in operative time, estimated blood loss, length of
      stay, and complications. There were no complications related to use of clips. In
      the clip group, staplers were used in 10% because base of appendix was too large,
      gangrenous, or perforated and could not be clipped. Use of polymeric clips was
      less expensive and generated less waste. CONCLUSIONS: Use of polymeric clips for
      appendectomy is safe and effective, and results are comparable with those of
      stapling. Based on our data, in 90% of appendectomies, the base of appendix is
      amenable to clipping. This study supports use of clips over staplers to decrease
      cost and environmental impact.

PMID- 30192170
TI  - Evaluation of Biomarkers in Multiple Ipsilateral Synchronous Invasive Breast
      Carcinomas.
AB  - CONTEXT: - The College of American Pathologists guidelines recommend testing
      additional tumor foci in multifocal invasive breast carcinomas for the biomarkers
      estrogen receptor (ER), progesterone receptor, and HER2, only if the carcinomas
      show different morphologies or grades. OBJECTIVE: - To assess clinical
      significance of testing for biomarkers in additional tumor foci in multifocal
      invasive breast tumors. DESIGN: - Retrospective analysis of 118 patients
      diagnosed with ipsilateral synchronous multifocal breast carcinomas from January
      2015 through March 2016 at Mount Sinai Hospital (New York, New York). RESULTS: -
      Eighty-six cases were tested for at least 1 of the 3 biomarkers in additional
      tumor foci. Fifteen cases (17%) showed discordant staining between the two foci
      for at least one biomarker. Of the 7 of 67 ER-discordant cases (10%), 4 (57%)
      showed major variation from negative to positive expression, including 3 cases in
      which a smaller tumor focus was strongly positive for ER whereas the index tumor
      was negative. Similarly, within the 7 of 67 progesterone receptor-discordant
      cases (10%), 4 (57%) showed major variation from negative to positive; and in 3
      cases with major discordance, the index tumor was negative for progesterone
      receptor, whereas a smaller focus was positive. A difference in HER2 expression
      was noted in 5 of 86 cases (6%). In only 5 of the 15 patients (33%) with
      discordant results, biomarker testing on additional foci would have been offered
      per the College of American Pathologists recommendations because of differences
      in histology or grading. Of the remaining 10 patients, 7 (70%) with positive
      results on smaller foci would have been deprived of appropriate adjuvant systemic
      treatment if the smaller focus had not been tested. CONCLUSIONS: - We propose
      that negative values expressed in the primary tumor be repeated routinely on
      additional ipsilateral synchronous tumors.

PMID- 30192171
TI  - Clinical Validation of Coexisting Activating Mutations Within EGFR, Mitogen
      Activated Protein Kinase, and Phosphatidylinositol 3-Kinase Pathways in Lung
      Cancers.
AB  - CONTEXT: - Mutations within the same signature transduction pathway are redundant
      and, therefore, most are mutually exclusive. Laboratory errors, however, may
      introduce unexpected coexisting mutations. OBJECTIVE: - To validate coexisting
      mutations within epidermal growth factor receptor (EGFR), mitogen-activated
      protein kinase, and phosphatidylinositol 3-kinase pathways. DESIGN: - In this
      retrospective study for quality assessment of next-generation sequencing in a
      clinical diagnostics setting, coexisting mutations within EGFR, KRAS, NRAS, BRAF,
      AKT1, and PIK3CA genes were examined in 1208 non-small cell lung cancers.
      RESULTS: - EGFR mutations did not coexist with BRAF mutations, neither kinase
      activated nor kinase-impaired mutations. There was a low but similar incidence
      (3.3%-5.1%) of PIK3CA mutations in BRAF-, EGFR-, and KRAS-mutated lung cancers
      and a rare incidence of coexisting KRAS and EGFR mutations detected in 1 of 1208
      lung cancers (0.08%) or 1 of 226 EGFR-mutated lung cancers (0.4%). Coexisting
      BRAF p.V600E mutation was observed in 3 of 4 AKT1 p.E17K-mutated lung cancers.
      Mutational profiling of DNA reisolated from subareas with the same or different
      histomorphology, using an alternative assay, confirmed that coexisting mutations
      might present within the same (whole or subclonal) population or different
      populations and clarified that the so-called coexisting activating KRAS and BRAF
      mutations originally reported in a specimen were indeed present in separate lung
      nodules submitted in the same block. CONCLUSIONS: - The results supported that
      EGFR and BRAF mutations are early driver mutations in lung cancers. Guidelines
      from official organizations to establish standard operating procedures are
      warranted to validate unexpected coexisting mutations and, if clinically
      indicated, to determine their presence in the same or different tumor
      populations.

PMID- 30192173
TI  - First Report of Boxwood Blight Caused by Calonectria pseudonaviculata in
      California.

PMID- 30192172
TI  - Laparoscopic Liver Resection with Augmented Reality: A Preclinical Experience.
AB  - INTRODUCTION: Intraoperative imaging, such as ultrasound, provides subsurface
      anatomical information not seen by standard laparoscopy. Currently, information
      from the two modalities may only be integrated in the surgeon's mind, an often
      distracting and inefficient task. The desire to improve intraoperative efficiency
      has guided the development of a novel, augmented reality (AR) laparoscopic system
      that integrates, in real time, laparoscopic ultrasound (LUS) images with the
      laparoscopic video. This study shows the initial application of this system for
      laparoscopic hepatic wedge resection in a porcine model. MATERIALS AND METHODS:
      The AR system consists of a standard laparoscopy setup, LUS scanner,
      electromagnetic tracking system, and a laptop computer for image fusion. Two
      liver lesions created in a 40-kg swine by radiofrequency ablation (RFA) were
      resected using the novel AR system and under standard laparoscopy. RESULTS:
      Anatomical details from the LUS were successfully fused with the laparoscopic
      video in real time and presented on a single screen for the surgeons. The RFA
      lesions created were 2.5 and 1 cm in diameter. The 2.5 cm lesion was resected
      under AR guidance, taking about 7 minutes until completion, while the 1 cm lesion
      required 3 minutes using standard laparoscopy and ultrasound. Resection margins
      of both lesions grossly showed noncoagulated liver parenchyma, indicating a
      negative-margin resection. CONCLUSIONS: The use of our AR system in laparoscopic
      hepatic wedge resection in a swine provided real-time integration of ultrasound
      image with standard laparoscopy. With more experience and testing, this system
      can be used for other laparoscopic procedures.

PMID- 30192174
TI  - Occurrence of Potato virus Y Recombinants, Strain PVYNTN, Infecting Tobacco in
      Pakistan.

PMID- 30192175
TI  - First Report of Root Rot of Nepeta cataria Caused by Macrophomina phaseolina in
      India.

PMID- 30192176
TI  - First Report of Root Rot of Aloe barbadensis Caused by Pythium spinosum in China.

PMID- 30192177
TI  - New Records of Rust Disease Caused by Uromyces halstedii in North America.

PMID- 30192178
TI  - First Report of Powdery Mildew Caused by Podosphaera xanthii on Lagenaria
      siceraria in China.

PMID- 30192180
TI  - First Report of Stemphylium lycopersici Causing Gray Leaf Spot on Potato in
      China.

PMID- 30192179
TI  - First Report of Ilyonectria robusta Causing Black Foot Disease of Grapevine in
      Spain.

PMID- 30192181
TI  - First Report of Charcoal Rot on Zebra Plant (Aphelandra squarrosa) Caused by
      Macrophomina phaseolina.

PMID- 30192182
TI  - First Report of Yerba Mate Wilt Caused by Ceratocystis fimbriata in Brazil.

PMID- 30192183
TI  - Effect of arteriovenous graft flow rate on vascular access hemodynamics in a
      novel modular anastomotic valve device.
AB  - PURPOSE: Perturbed vascular access hemodynamics is considered a potential driver
      of intimal hyperplasia, the leading cause of vascular access failure. To improve
      vascular access patency, a modular anastomotic valve device has been designed to
      normalize venous flow between hemodialysis periods while providing normal
      vascular access during hemodialysis. The objective of this study was to quantify
      the effects of arteriovenous graft flow rate on modular anastomotic valve device
      vascular access hemodynamics under realistic hemodialysis conditions. METHODS:
      Modular anastomotic valve device inlet and outlet flow conditions and velocity
      profiles were measured by ultrasound Doppler in a vascular access flow loop
      replicating arteriovenous graft flow rates of 800, 1000, and 1500 mL/min. Fluid
      structure interaction simulations were performed to identify low wall shear
      stress regions on the vein wall and to characterize them in terms of temporal
      shear magnitude, oscillatory shear index, and relative residence time. The model
      was validated with respect to the Doppler measurements. RESULTS: The low wall
      shear stress region generated downstream of the anastomosis under low and
      moderate arteriovenous graft flow rates was eliminated under the highest
      arteriovenous graft flow rate. Increase in arteriovenous graft flow rate from 800
      to 1500 mL/min resulted in a substantial increase in wall shear stress magnitude
      (27-fold increase in temporal shear magnitude), the elimination of wall shear
      stress bidirectionality (0.20-point reduction in oscillatory shear index), and a
      reduction in flow stagnation (98% decrease in relative residence time). While the
      results suggest the ability of high arteriovenous graft flow rates to protect the
      venous wall from intimal hyperplasia-prone hemodynamics, they indicate their
      adverse impact on the degree of venous hemodynamic abnormality.

PMID- 30192184
TI  - Efforts and Opportunities to Understand Women's Mortality Due to Suicide and
      Homicide Using the National Violent Death Reporting System.
AB  - Women's mortality due to violent deaths is a public health issue that has
      received national attention. Many data systems only collect death certificate
      data, which provide very limited information about the circumstances surrounding
      a violent death. The Centers for Disease Control and Prevention's (CDC's)
      National Violent Death Reporting System (NVDRS) is the first and only
      surveillance system to capture data from death certificates, coroner/medical
      examiner reports, and law enforcement reports allowing for a more comprehensive
      picture and targeted prevention efforts. The system currently operates in 40
      states, the District of Columbia, and Puerto Rico; however, with additional
      funding from the Consolidated Appropriations Act of 2018, this surveillance
      system will fully expand to cover all 50 states. A number of analyses have been
      conducted using NVDRS data to compare suicide and homicide among women with men;
      however, only a handful of studies have been conducted among subgroups of women.
      The present study provides an overview of NVDRS while highlighting a few key
      analytic studies with implications for suicide and homicide
      prevention/intervention among women. Data from the 2014 NVDRS Surveillance
      Summary are also presented to emphasize the unique opportunity to use NVDRS data
      to study the characteristics of suicide and homicide among women. The summary
      includes data from 18 states that were collected statewide. This information can
      provide state and local public health experts with essential data on female
      suicide and homicide, not provided in other surveillance systems, to help shape
      prevention and intervention efforts.

PMID- 30192185
TI  - Item statistics derived from three-option versions of multiple-choice questions
      are usually as robust as four- or five-option versions: implications for exam
      design.
AB  - Different versions of multiple-choice exams were administered to an undergraduate
      class in human physiology as part of normal testing in the classroom. The goal
      was to evaluate whether the number of options (possible answers) per question
      influenced the effectiveness of this assessment. Three exams (each with three
      versions) were given to each of two sections during an academic quarter. All
      versions were equally long, with 30 questions: 10 questions with 3 options, 10
      questions with 4, and 10 questions with 5 (always one correct answer plus
      distractors). Each question appeared in all three versions of an exam, with a
      different number of options in each version (three, four, or five).
      Discrimination (point biserial and upper-lower discrimination indexes) and
      difficulty were evaluated for each question. There was a small increase in
      difficulty (a lower average score on a question) when more options were provided.
      The upper-lower discrimination index indicated a small improvement in assessment
      of student learning with more options, although the point biserial did not. The
      total length of a question (number of words) was associated with a small increase
      in discrimination and difficulty, independent of the number of options.
      Quantitative questions were more likely to show an increase in discrimination
      with more options than nonquantitative questions, but this effect was very small.
      Therefore, for these testing conditions, there appears to be little advantage in
      providing more than three options per multiple-choice question, and there are
      disadvantages, such as needing more time for an exam.

PMID- 30192186
TI  - Status of research on physiology education in Brazil.
AB  - Physiology education research aims to investigate teaching-learning aspects and
      methods specifically applied to physiology teaching and learning. In this paper
      exploring Brazilian research public data and information from the Brazilian
      Physiological Society Teaching Committee, we investigated the status of this
      research topic (physiology education) in Brazil. The data showed that physiology
      education research needs to be more recognized and supported in Brazil, and more
      physiologists may become interested in research in this field. Thus this field
      will become more developed during the physiologists' education.

PMID- 30192187
TI  - Recall of physiology knowledge among medical interns: an exploratory study in
      Riyadh, Saudi Arabia.
AB  - The aim of the study was to explore the factors associated with the recall of
      basic medical physiology knowledge among medical interns and to determine the
      level of retained basic science knowledge. Two hundred and four interns, 114
      women and 90 men, working in two major tertiary medical care centers, King Fahad
      Medical City (KFMC; 29 students) and King Khalid University Hospital (KKUH; 117
      students), in Riyadh city, participated in the study. An anonymous knowledge test
      with 10 validated multiple-choice questions was developed specifically for this
      purpose. One hundred and forty-six interns (117 working at KKUH and 29 at KFMC)
      had graduated from medical schools adopting a conventional instructional system,
      whereas 58 (3 from KKUH and 55 from KFMC had graduated from schools adopting an
      integrated system (hybrid problem-based learning). Fifty-two students (26%)
      gained a score >=60%, whereas 152 students (74%) obtained <60% of the score.
      Higher scores were associated with younger age ( P < 0.01), traditional
      curriculum ( P < 0.001), interns from KKUH ( P < 0.001), and candidates for
      postgraduate studies ( P < 0.02). There was no significant association between
      recall of physiology knowledge and all other variables studied, including sex.
      Multivariate analyses show that age and traditional curriculum are the only
      significant predictors of knowledge retention. Almost three-fourths of the
      interns scored <60%, and higher scores were significantly associated with younger
      interns, traditional curriculum, working in KKUH, and interns preparing for
      graduate studies. However, the difference between the two curricula disappears
      when the influence of hospital training is considered.

PMID- 30192188
TI  - The physiology of impenetrable skin: Colossus of the X-Men.
AB  - The X-Men are an ensemble of superheroes whose powers are associated with the X
      Gene, a mutant genetic factor. The powers exhibited by each character differ and
      are dependent on how the X-Gene has modified their individual genomes. For
      instance, Wolverine possesses regenerative healing, Storm can control local
      weather systems, and Colossus can create an impenetrable "organic steel" layer
      around his body. Thanks to the establishment of the superhero genre in modern
      cinema, audiences are familiar with Colossus from films such as X-Men: Days of
      Future Past and Deadpool. While attaining this power might be attractive to many
      people, there are innumerate scientific obstacles to be overcome to replicate
      this "organic steel" layer. Due to its unique combination of high strength and
      flexibility, a graphene-based layer might be a more realistic material for
      Colossus' impenetrable skin and would also address a number of physiological
      issues associated with an "organic steel" layer. The actualization of this layer
      would depend on complex processes associated with protein folding, protein self
      assembly, and changing the structure of his skin. In the classroom, Colossus can
      foster a multidisciplinary learning environment where concepts in physiology can
      overlap with topics in physics, engineering, and materials science. Just like
      other superheroes, Colossus can also be used to promote scientific content in
      outreach for the general public.

PMID- 30192189
TI  - How do students deal with difficult physiological knowledge?
AB  - Physiology courses are considered to be challenging for students to master due to
      the highly conceptual nature of the discipline and the substantial cognitive
      effort required to understand disciplinary knowledge. Students must choose
      appropriate learning strategies to develop their understanding, as their choices
      may influence both their understanding and their academic achievement. The
      primary aim of this study was to develop an understanding of why students
      experience difficulties with physiology and how they respond when facing the
      challenge of learning this discipline. Undergraduate allied health students ( n =
      231) studying physiology were asked to identify the topics they had difficulty
      understanding, the strategies they used to deal with that difficult knowledge,
      and the reasons for their difficulties. Consenting students' responses were
      subjected to inductive and deductive thematic analyses, and their performance on
      examinations were collated. Students reported that they found physiology
      difficult due to their lack of familiarity with it and the level of detail
      required. To aid their understanding of difficult topics, students commonly
      reported reviewing information, seeking further information, and seeking social
      assistance, with more high-achieving students reporting reviewing records, and
      fewer reporting seeking social assistance than poor-achieving students. Most
      notably, a disconnect was found between students' reporting of difficult modules
      and their academic achievement on those modules, with students who cited
      difficulties performing equally well, if not better, than those who do not.
      Importantly, these findings suggest that students, in recognizing their
      difficulties and the reasons for them, can implement effective learning
      strategies to overcome them.

PMID- 30192190
TI  - Limitations of median nerve somatosensory evoked potential monitoring during
      carotid endarterectomy.
AB  - OBJECTIVE Hypoperfusion during carotid artery cross-clamping (CC) for carotid
      endarterectomy (CEA) may result in the major complication of perioperative
      stroke. Median nerve somatosensory evoked potential (MNSSEP) monitoring, which is
      an established method for the prediction of cerebral ischemia, has low
      sensitivity in detecting such hypoperfusion. In this study the authors sought to
      explore the limitations of MNSSEP monitoring compared to tibial nerve
      somatosensory evoked potential (TNSSEP) monitoring for the detection of CC
      related hypoperfusion. METHODS The authors retrospectively analyzed data from
      patients who underwent unilateral CEA with routine shunt use. All patients
      underwent preoperative magnetic resonance angiography and were monitored for
      intraoperative cerebral ischemia by using MNSSEP, TNSSEP, and carotid stump
      pressure during CC. First, the frequency of MNSSEP and TNSSEP changes during CC
      were analyzed. Subsequently, variables related to stump pressure were determined
      by using linear analysis and those related to each of the somatosensory evoked
      potential (SSEP) changes were determined by using logistic regression analysis.
      RESULTS A total of 94 patients (mean age 74 years) were included in the study.
      TNSSEP identified a greater number of SSEP changes during CC than MNSSEP (20.2%
      vs 11.7%; p < 0.05). Linear regression analysis demonstrated that hypoplasia of
      the contralateral proximal segment of the anterior cerebral artery (A1
      hypoplasia) (p < 0.01) and hypoplasia of the ipsilateral precommunicating segment
      of the posterior cerebral artery (P1 hypoplasia) (p = 0.02) independently and
      negatively correlated with stump pressure. Both contralateral A1 hypoplasia (OR
      26.25, 95% CI 4.52-152.51) and ipsilateral P1 hypoplasia (OR 8.75, 95% CI 1.83
      41.94) were independently related to the TNSSEP changes. However, only
      ipsilateral P1 hypoplasia (OR 8.76, 95% CI 1.61-47.67) was independently related
      to MNSSEP changes. CONCLUSIONS TNSSEP monitoring appears to be superior to MNSSEP
      in detecting CC-related hypoperfusion. Correlation with stump pressure and SSEP
      changes indicates that TNSSEP, and not MNSSEP monitoring, is a reliable indicator
      of cerebral ischemia in the territory of the anterior cerebral artery.

PMID- 30192191
TI  - The medial wall of the cavernous sinus. Part 2: Selective medial wall resection
      in 50 pituitary adenoma patients.
AB  - OBJECTIVE Pituitary adenomas often invade the medial wall of the cavernous sinus
      (CS), but this structure is generally not surgically removed because of the risk
      of vascular and cranial nerve injury. The purpose of this study was to report the
      surgical outcomes in a large series of cases of invasive pituitary adenoma in
      which the medial wall of the CS was selectively removed following an anatomically
      based, stepwise surgical technique. METHODS The authors' institutional database
      was reviewed to identify cases of pituitary adenoma with isolated invasion of the
      medial wall, based on an intraoperative evaluation, in which patients underwent
      an endoscopic endonasal approach with selective resection of the medial wall of
      the CS. Cases with CS invasion beyond the medial wall were excluded. Patient
      complications, resection, and remission rates were assessed. RESULTS Fifty
      patients were eligible for this study, 15 (30%) with nonfunctional adenomas and
      35 (70%) with functional adenomas, including 16 growth hormone-, 10 prolactin-,
      and 9 adrenocorticotropic hormone (ACTH)-secreting tumors. The average tumor size
      was 2.3 cm for nonfunctional and 1.3 cm for functional adenomas.
      Radiographically, 11 cases (22%) were Knosp grade 1, 23 (46%) Knosp grade 2, and
      16 (32%) Knosp grade 3. Complete tumor resection, based on intraoperative
      impression and postoperative MRI, was achieved in all cases. The mean follow-up
      was 30 months (range 4-64 months) for patients with functional adenomas and 16
      months (range 4-30 months) for those with nonfunctional adenomas. At last follow
      up, complete biochemical remission (using current criteria) without adjuvant
      treatment was seen in 34 cases (97%) of functional adenoma. No imaging
      recurrences were seen in patients who had nonfunctional adenomas. A total of 57
      medial walls were removed in 50 patients. Medial wall invasion was histologically
      confirmed in 93% of nonfunctional adenomas and 83% of functional adenomas. There
      were no deaths or internal carotid artery injuries, and the average blood loss
      was 378 ml. Four patients (8%) developed a new, transient cranial nerve palsy,
      and 2 of these patients required reoperation for blood clot evacuation and fat
      graft removal. There were no permanent cranial nerve palsies. CONCLUSIONS The
      medial wall of the CS can be removed safely and effectively, with minimal
      morbidity and excellent resection and remission rates. Further follow-up is
      needed to determine the long-term results of this anatomically based technique,
      which should only be performed by very experienced endonasal skull base teams.

PMID- 30192192
TI  - The medial wall of the cavernous sinus. Part 1: Surgical anatomy, ligaments, and
      surgical technique for its mobilization and/or resection.
AB  - OBJECTIVE The medial wall of the cavernous sinus (CS) is often invaded by
      pituitary adenomas. Surgical mobilization and/or removal of the medial wall
      remains a challenge. METHODS Endoscopic endonasal dissection was performed in 20
      human cadaver heads. The configuration of the medial wall, its relationship to
      the internal carotid artery (ICA), and the ligamentous connections in between
      them were investigated in 40 CSs. RESULTS The medial wall of the CS was confirmed
      to be an intact single layer of dura that is distinct from the capsule of the
      pituitary gland and the periosteal layer that forms the anterior wall of the CS.
      In 32.5% of hemispheres, the medial wall was indented by and/or well adhered to
      the cavernous ICA. The authors identified multiple ligamentous fibers that
      anchored the medial wall to other walls of the CS and/or to specific ICA
      segments. These parasellar ligaments were classified into 4 groups: 1)
      caroticoclinoid ligament, spanning from the medial wall and the middle clinoid
      toward the clinoid ICA segment and anterior clinoid process; 2) superior
      parasellar ligament, connecting the medial wall to the horizontal cavernous ICA
      and/or lateral wall of the CS; 3) inferior parasellar ligament, bridging the
      medial wall to the anterior wall of the CS or anterior surface of the short
      vertical segment of the cavernous ICA; and 4) posterior parasellar ligament,
      which anchors the medial wall to the short vertical segment of the cavernous ICA
      and/or the posterior carotid sulcus. The caroticoclinoid ligament and inferior
      parasellar ligament were present in most CSs (97.7% and 95%, respectively), while
      the superior and posterior parasellar ligaments were identified in approximately
      half of the CSs (57.5% and 45%, respectively). The caroticoclinoid ligament was
      the strongest and largest ligament, and it was typically assembled as a group of
      ligaments with a fan-like arrangement. The inferior parasellar ligament was the
      first to be encountered after opening the anterior wall of the CS during an
      interdural transcavernous approach. CONCLUSIONS The authors introduce a
      classification of the parasellar ligaments and their role in anchoring the medial
      wall of the CS. These ligaments should be identified and transected to safely
      mobilize the medial wall away from the cavernous ICA during a transcavernous
      approach and for safe and complete resection of adenomas that selectively invade
      the medial wall.

PMID- 30192193
TI  - Nervus intermedius dysfunctions after vestibular schwannoma surgery: a
      prospective clinical study.
AB  - OBJECTIVE The purpose of this prospective study was to evaluate the dysfunction
      of the nervus intermedius (NI) after vestibular schwannoma (VS) surgery. The
      authors present a clinically feasible method for this purpose. METHODS In this
      prospective study, the authors included 30 patients who underwent surgery at the
      International Neuroscience Institute between May 2014 and February 2017 for
      resection of VS. The patients' taste sensation was examined using taste strips.
      Lacrimation was tested using the Schirmer I test. The clinical evaluation was
      performed before surgery and repeated at 2 weeks and at 6 months after surgery as
      well as during the follow-up, which extended up to 2 years. The authors tested
      the correlation between the NI dysfunctions and the House-Brackmann grade of
      facial nerve palsy. RESULTS The taste sensation was lost on the side of surgery
      in 2 patients (6.6%) and decreased in 4 patients (13.3%). The disturbance of
      taste sensation was not statistically correlated with dysfunctions of the motor
      portion of the facial nerve. The taste impairment resolved in 4 patients within 6
      months, but 2 patients suffered from persistent loss of the taste sensation on
      the side of surgery during the follow-up. In 23 patients (76.6%), the baseline
      lacrimation was lower on the side of surgery, and it was significantly correlated
      with outcome for dysfunctions of the motor portion of the facial nerve. During
      the follow-up, baseline lacrimation improved in correlation with the improvement
      in the dysfunctions of the motor portion of the facial nerve. None of the
      patients reported change in salivation or nasal secretion. CONCLUSIONS The NI can
      be affected after VS surgery. The disturbance of baseline lacrimal secretion was
      correlated with dysfunctions of the motor portion of the facial nerve. However,
      the disturbance of the taste sensation was not correlated with the grade of
      facial nerve palsy. Dysfunctions of the NI should be evaluated and separately
      reported while analyzing facial nerve outcome after VS surgery.

PMID- 30192194
TI  - Letter to the Editor. Middle cerebral artery tortuosity associated with aneurysm
      development.

PMID- 30192195
TI  - Comparison of treatment results between 3- and 2-stage Gamma Knife radiosurgery
      for large brain metastases: a retrospective multi-institutional study.
AB  - OBJECTIVE In order to obtain better local tumor control for large (i.e., > 3 cm
      in diameter or > 10 cm3 in volume) brain metastases (BMs), 3-stage and 2-stage
      Gamma Knife surgery (GKS) procedures, rather than a palliative dose of
      stereotactic radiosurgery, have been proposed. Here, authors conducted a
      retrospective multi-institutional study to compare treatment results between 3
      stage and 2-stage GKS for large BMs. METHODS This retrospective multi
      institutional study involved 335 patients from 19 Gamma Knife facilities in
      Japan. Major inclusion criteria were 1) newly diagnosed BMs, 2) largest tumor
      volume of 10.0-33.5 cm3, 3) cumulative intracranial tumor volume <= 50 cm3, 4) no
      leptomeningeal dissemination, 5) no more than 10 tumors, and 6) Karnofsky
      Performance Status 70% or better. Prescription doses were restricted to between
      9.0 and 11.0 Gy in 3-stage GKS and between 11.8 and 14.2 Gy in 2-stage GKS. The
      total treatment interval had to be within 6 weeks, with at least 12 days between
      procedures. There were 114 cases in the 3-stage group and 221 in the 2-stage
      group. Because of the disproportion in patient numbers and the pre-GKS clinical
      factors between these two GKS groups, a case-matched study was performed using
      the propensity score matching method. Ultimately, 212 patients (106 from each
      group) were selected for the case-matched study. Overall survival, tumor
      progression, neurological death, and radiation-related adverse events were
      analyzed. RESULTS In the case-matched cohort, post-GKS median survival time
      tended to be longer in the 3-stage group (15.9 months) than in the 2-stage group
      (11.7 months), but the difference was not statistically significant (p = 0.65).
      The cumulative incidences of tumor progression (21.6% vs 16.7% at 1 year, p =
      0.31), neurological death (5.1% vs 6.0% at 1 year, p = 0.58), or serious
      radiation-related adverse events (3.0% vs 4.0% at 1 year, p = 0.49) did not
      differ significantly. CONCLUSIONS This retrospective multi-institutional study
      showed no differences between 3-stage and 2-stage GKS in terms of overall
      survival, tumor progression, neurological death, and radiation-related adverse
      events. Both 3-stage and 2-stage GKS performed according to the aforementioned
      protocols are good treatment options in selected patients with large BMs.

PMID- 30192196
TI  - A refined model of chronic cerebral hypoperfusion resulting in cognitive
      impairment and a low mortality rate in rats.
AB  - OBJECTIVE The cognitive deficits of vascular dementia and the vasoocclusive state
      of moyamoya disease have often been mimicked with bilateral stenosis/occlusion of
      the common carotid artery (CCA) or internal carotid artery. However, the cerebral
      blood flow (CBF) declines abruptly in these models after ligation of the CCA,
      which differs from "chronic" cerebral hypoperfusion. While some modified but time
      consuming techniques have used staged occlusion of both CCAs, others used
      microcoils for CCA stenosis, producing an adverse effect on the arterial
      endothelium. Thus, the authors developed a new chronic cerebral hypoperfusion
      (CCH) model with cognitive impairment and a low mortality rate in rats. METHODS
      Male Sprague-Dawley rats were subjected to unilateral CCA occlusion and
      contralateral induction of CCA stenosis (modified CCA occlusion [mCCAO]) or a
      sham operation. Cortical regional CBF (rCBF) was measured using laser speckle
      flowmetry. Cognitive function was assessed using a Barnes circular maze (BCM).
      MRI studies were performed 4 weeks after the operation to evaluate cervical and
      intracranial arteries and parenchymal injury. Behavioral and histological studies
      were performed at 4 and 8 weeks after surgery. RESULTS The mCCAO group revealed a
      gradual CBF reduction with a low mortality rate (2.3%). White matter degeneration
      was evident in the corpus callosum and corpus striatum. Although the cellular
      density declined in the hippocampus, MRI revealed no cerebral infarctions after
      mCCAO. Immunohistochemistry revealed upregulated inflammatory cells and
      angiogenesis in the hippocampus and cerebral cortex. Results of the BCM
      assessment indicated significant impairment in spatial learning and memory in the
      mCCAO group. Although some resolution of white matter injury was observed at 8
      weeks, the animals still had cognitive impairment. CONCLUSIONS The mCCAO is a
      straightforward method of producing a CCH model in rats. It is associated with a
      low mortality rate and could potentially be used to investigate vascular disease,
      moyamoya disease, and CCH. This model was verified for an extended time point of
      8 weeks after surgery.

PMID- 30192197
TI  - Utility and safety of depth electrodes within the supratemporal plane for
      intracranial EEG.
AB  - OBJECTIVE The epileptogenic zones in some patients with temporal lobe epilepsy
      (TLE) involve regions outside the typical extent of anterior temporal lobectomy
      (i.e., "temporal plus epilepsy"), including portions of the supratemporal plane
      (STP). Failure to identify this subset of patients and adjust the surgical plan
      accordingly results in suboptimum surgical outcomes. There are unique technical
      challenges associated with obtaining recordings from the STP. The authors sought
      to examine the clinical utility and safety of placing depth electrodes within the
      STP in patients with TLE. METHODS This study is a retrospective review and
      analysis of all cases in which patients underwent intracranial
      electroencephalography (iEEG) with use of at least one STP depth electrode over
      the 10 years from January 2006 through December 2015 at University of Iowa
      Hospitals and Clinics. Basic clinical information was collected, including the
      presence of ictal auditory symptoms, electrode coverage, monitoring results,
      resection extent, outcomes, and complications. Additionally, cases in which the
      temporal lobe was primarily or secondarily involved in seizure onset and
      propagation were categorized based upon how rapidly epileptic activity was
      observed within the STP following seizure onsets: within 1 second, between 1 and
      15 seconds, after 15 seconds, and not involved. RESULTS Fifty-two patients
      underwent iEEG with STP coverage, with 1 STP electrode used in 45 (86.5%) cases
      and 2 STP electrodes in the other cases. There were no complications related to
      STP electrode placement. Of 42 cases in which the temporal lobe was primarily or
      secondarily involved, seizure activity was recorded from the STP in 36 cases
      (85.7%): in 5 cases (11.9%) within 1 second, in 5 (11.9%) between 1 and 15
      seconds, and in 26 (61.9%) more than 15 seconds following seizure onset. Seizure
      outcomes inversely correlated with rapid ictal involvement of the STP (Engel
      class I achieved in 25%, 67%, and 82% of patients in the above categories,
      respectively). All patients without ictal STP involvement achieved seizure
      freedom. Only 4 (11.1%) patients with STP ictal involvement reported auditory
      symptoms. CONCLUSIONS Ictal involvement of the STP is common even in the absence
      of auditory symptoms and can be effectively detected by the STP electrodes. These
      electrodes are safe to implant and provide useful prognostic information.

PMID- 30192198
TI  - Letter to the Editor. Gamma Knife surgery for trigeminal pain due to benign and
      malignant skull base tumors.

PMID- 30192199
TI  - A comparison between threshold criterion and amplitude criterion in transcranial
      motor evoked potentials during surgery for supratentorial lesions.
AB  - OBJECTIVE The aim of this study was to compare sensitivity and specificity
      between the novel threshold and amplitude criteria for motor evoked potentials
      (MEPs) monitoring after transcranial electrical stimulation (TES) during surgery
      for supratentorial lesions in the same patient cohort. METHODS One hundred twenty
      six patients were included. All procedures were performed under general
      anesthesia. Craniotomies did not expose motor cortex, so that direct mapping was
      less suitable. After TES, MEPs were recorded bilaterally from abductor pollicis
      brevis (APB), from orbicularis oris (OO), and/or from tibialis anterior (TA). The
      percentage increase in the threshold level was assessed and considered
      significant if it exceeded by more than 20% on the affected side the percentage
      increase on the unaffected side. Amplitude on the affected side was measured with
      a stimulus intensity of 150% of the threshold level set for each muscle. RESULTS
      Eighteen of 126 patients showed a significant change in the threshold level as
      well as an amplitude reduction of more than 50% in MEPs recorded from APB, and 15
      of the patients had postoperative deterioration of motor function of the arm
      (temporary in 8 cases and permanent in 7 [true-positive and false-negative
      results]). Recording from TA was performed in 66 patients; 4 developed
      postoperative deterioration of motor function of the leg (temporary in 3 cases
      and permanent in 1), and showed a significant change in the threshold level, and
      an amplitude reduction of more than 50% occurred in 1 patient. An amplitude
      reduction of more than 50% occurred in another 10 patients, without a significant
      change in the threshold level or postoperative deterioration. Recording from OO
      was performed in 61 patients; 3 developed postoperative deterioration of motor
      function of facial muscles (temporary in 2 cases and permanent in 1) and had a
      significant change in the threshold level, and 2 of the patients had an amplitude
      reduction of more than 50%. Another 6 patients had an amplitude reduction of more
      than 50% but no significant change in the threshold level or postoperative
      deterioration. Sensitivity of the threshold criterion was 100% when MEPs were
      recorded from APB, OO, or TA, and its specificity was 97%, 100%, and 100%,
      respectively. Sensitivity of the amplitude criterion was 100%, 67%, and 25%, with
      a specificity of 97%, 90%, and 84%, respectively. CONCLUSIONS The threshold
      criterion was comparable to the amplitude criterion with a stimulus intensity set
      at 150% of the threshold level regarding sensitivity and specificity when
      recording MEPs from APB, and superior to it when recording from TA or OO.

PMID- 30192200
TI  - Elucidating the kinetics of sodium fluorescein for fluorescence-guided surgery of
      glioma.
AB  - OBJECTIVE The use of the optical contrast agent sodium fluorescein (NaFl) to
      guide resection of gliomas has been under investigation for decades. Although
      this imaging strategy assumes the agent remains confined to the vasculature
      except in regions of blood-brain barrier (BBB) disruption, clinical studies have
      reported significant NaFl signal in normal brain tissue, limiting tumor-to-normal
      contrast. A possible explanation arises from earlier studies, which reported that
      NaFl exists in both pure and protein-bound forms in the blood, the former being
      small enough to cross the BBB. This study aims to elucidate the kinetic binding
      behavior of NaFl in circulating blood and its effect on NaFl accumulation in
      brain tissue and tumor contrast. Additionally, the authors examined the blood and
      tissue kinetics, as well as tumor uptake, of a pegylated form of fluorescein
      selected as a potential optical analog of gadolinium-based MRI contrast agents.
      METHODS Cohorts of mice were administered one of the following doses/forms of
      NaFl: 1) high human equivalent dose (HED) of NaFl, 2) low HED of NaFl, or 3)
      pegylated form of fluorescein. In each cohort, groups of animals were euthanized
      15, 30, 60, and 120 minutes after administration for ex vivo analysis of
      fluorescein fluorescence. Using gel electrophoresis and fluorescence imaging of
      blood and brain specimens, the authors quantified the temporal kinetics of bound
      NaFl, unbound NaFl, and pegylated fluorescein in the blood and normal brain
      tissue. Finally, they compared tumor-to-normal contrast for NaFl and pegylated
      fluorescein in U251 glioma xenografts. RESULTS Administration of NaFl resulted in
      the presence of unbound and protein-bound NaFl in the circulation, with unbound
      NaFl constituting up to 70% of the signal. While protein-bound NaFl was
      undetectable in brain tissue, unbound NaFl was observed throughout the brain. The
      observed behavior was time and dose dependent. The pegylated form of fluorescein
      showed minimal uptake in brain tissue and improved tumor-to-normal contrast by
      38%. CONCLUSIONS Unbound NaFl in the blood crosses the BBB, limiting the
      achievable tumor-to-normal contrast and undermining the inherent advantage of
      tumor imaging in the brain. Dosing and incubation time should be considered
      carefully for NaFl-based fluorescence-guided surgery (FGS) of glioma. A pegylated
      form of fluorescein showed more favorable normal tissue kinetics that translated
      to higher tumor-to-normal contrast. These results warrant further development of
      pegylated-fluorescein for FGS of glioma.

PMID- 30192202
TI  - Big Data Based m-Health Application to Prevent Health Hazards: A Design Science
      Framework.
AB  - BACKGROUND: Every year about three million Muslims visit the Holy City of Makkah
      in Saudi Arabia to perform the Hajj. Because of the large number of people
      present during this period, pilgrims can be subjected to many health hazards. An
      adequate system to minimize these health hazards is needed to support the
      pilgrims who attend the Hajj. This study justifies the need for developing a
      large data-based m-Health application to identify the health hazards encountered
      during the Hajj. MATERIALS AND METHODS: In developing a big data-based m-Health
      application, this study follows the framework suggested by Hevner. The design of
      the science framework allows the development of a technological solution (i.e.,
      design artifact) of the problem through a series of actions. The design involves
      rigorous knowledge of the environmental factors, including knowledge of the
      construction and evaluation of technological solutions, that are important and
      relevant to an existing problem. RESULTS: Based on the design science framework,
      the process of artifact development can be classified into Artifact Design,
      Artifact Implementation, and Artifact Evaluation. This paper presents the
      Artifact Design step for the design of the big data-based m-Health application,
      which has an Environmental Relevance Cycle, a Knowledge-based rigor Cycle, and an
      Artifice development and design cycle. The big data-based m-Health application is
      a prototype and must be evaluated using the evaluation-and-feedback loop process
      until the optimum artifact is completely built and integrated into the system.
      CONCLUSION: Development of a big data-based m-Health application using a design
      science framework can support the effective and comprehensive plan of the
      government of Saudi Arabia for preventing and managing Hajj-related health
      issues. Our proposed model for developing and designing a big data-based m-Health
      application could provide direction for developing the most advanced solution for
      dealing with the Hajj-related health issues in the future.

PMID- 30192201
TI  - Prevalence and Perceived Acceptability of Nongenital Sexually Transmitted
      Infection Testing in a Cohort of Young Transgender Women.
AB  - PURPOSE: This study documents the prevalence and acceptability of self-reported
      nongenital sexually transmitted infection (STI) testing among young transgender
      women (n = 72). METHODS: Bivariate analyses assessed differences in outcomes by
      demographic and behavioral characteristics. RESULTS: Less than half of
      participants self-reported nongenital STI testing (43% rectal; 44% pharyngeal).
      More than half of the sample reported that they would not find self-collection of
      specimens uncomfortable/unpleasant (53% rectal; 62% pharyngeal). No differences
      were found between demographics and prevalence of nongenital STI testing; those
      reporting condomless receptive anal sex were more likely to report previous
      pharyngeal testing. CONCLUSION: Future studies should document prevalence of
      nongenital STIs among transgender women.

PMID- 30192203
TI  - Use of Physician-Guided Patient Self-Examination to Diagnose Appendicitis: A
      Telemedicine Case Report.
AB  - BACKGROUND: Direct-to-consumer (DTC) telemedicine platforms have been
      increasingly implemented by large hospital systems. This care delivery mechanism
      shares similarities with bedside medical care, but also differs in key attributes
      such as the inability to perform a "hands-on" physical examination. METHODS: We
      present a case of DTC telehealth evaluation that resulted in the diagnosis of
      acute appendicitis. The case of one female patient presenting to our urgent care
      mobile application and subsequently to the emergency department (ED) is
      discussed. RESULTS: Physician-guided patient self-examination of the abdomen
      demonstrated concordance with findings on bedside physical examination in the ED,
      leading to the correct diagnosis of acute appendicitis. CONCLUSIONS: For the
      patient presented here, physician-guided patient self-examination resulted in
      appropriate referral to the ED and diagnosis of appendicitis. Additional research
      on the reproducibility of virtual physical examination findings and potential
      cost savings of telemedicine visits is warranted.

PMID- 30192204
TI  - Impact of diabetes mellitus on early outcome of carotid endarterectomy.
AB  - BACKGROUND: Diabetes mellitus increases the risk of ischaemic stroke in the
      general population but its impact on early outcome after the carotid
      endarterectomy (CEA) is controversial with conflicting results. PATIENTS AND
      METHODS: This prospective study includes 902 consecutive CEAs. Patients were
      divided into non-diabetic and diabetic groups and subsequently analysed. Early
      outcomes in terms of 30-day stroke and death rates were then analysed and
      compared. RESULTS: There were 606 non-diabetic patients. Among 296 diabetic
      patients, 83 were insulin-dependent. The cumulative TIA/stroke rate was
      statistically higher in the diabetic group (2.6 vs. 5.7 %, P = 0.02). Stroke was
      more frequent in the diabetic group (2.0 vs. 4.4 %, P = 0.04) comparedto TIA (0.7
      vs. 1.4 %, P = 0.45). Mortality was statistically more frequent in diabetic
      patients (0.2 vs. 1.7 %, P = 0.01). The 30-day stroke/death rate (2.6 vs. 5.7 %,
      P = 0.02) was also statistically higher in the diabetic group. Factors that were
      identified to increase risk of death and stroke in multivariate analysis were:
      use of insulin for blood glucose control (OR = 2.47, 95 % CI 1.61-4.68, P =
      0.01), higher low-density lipoprotein cholesterol value (OR = 1.52, 95 % CI 1.15
      2.22, P < 0.01), presence of coronary disease (OR = 2.04, 95 % CI 1.40-3.31, P =
      0.03), peripheral artery disease (OR = 2.14, 95 % CI 1.34-3.65, P = 0.02),
      complicated plaque (OR = 1.77, 95 % CI 1.11-3.68, P = 0.03), contralateral
      carotid artery occlusion (OR = 2.37, 95 % CI 1.25-4.74, P = 0.02), shunt use (OR
      = 3.46, 95 % CI 1.18-7.10, P < 0.01), and among diabetic patients higher HbA1c
      levels (OR = 1.28, 95 % CI 1.05-1.66, P = 0.03). Clamp toleration was associated
      with lower risk of death and stroke rates (OR = 0.43, 95 % CI 0.23-0.76, P <
      0.01). CONCLUSIONS: In our study, perioperative neurological complications and
      mortality were statistically higher in diabetic patients compared to non-diabetic
      patients during CEA. Further research will have to show whether other treatment
      modalities of carotid artery stenosis and better glycaemia and dyslipidaemia
      controlling in diabetics can reduce this risk.

PMID- 30192205
TI  - Serum MMP-8 and TIMP-1 as prognostic biomarkers in gastric cancer.
AB  - Despite gastric cancer being rare nowadays in Western countries, it remains one
      of the leading causes of cancer death worldwide. The course of the disease
      varies, so the individual gastric cancer patient's prognosis is difficult to
      determine. The need for new biomarkers is crucial. The aim of this study was to
      evaluate the prognostic value of serum matrix metalloproteinase-8, serum tissue
      inhibitor of metalloproteinase-1, and tissue matrix metalloproteinase-8 in
      patients with gastric cancer. Preoperative serum samples from 233 patients with
      gastric cancer were retrospectively analyzed. Serum levels of matrix
      metalloproteinase-8 were analyzed with immunofluorometric assay, and tissue
      inhibitor of metalloproteinase-1 levels were determined by enzyme-linked
      immunosorbent assay. We also determined the tissue expression of matrix
      metalloproteinase-8 in 276 gastric cancer samples by immunohistochemistry.
      Survival data and death causes came from patient records, the Population Register
      Center of Finland, and Statistics Finland. Patients with a low (<31 ng/mL) or
      high (>131 ng/mL) serum matrix metalloproteinase-8 level had a considerably
      unfavorable prognosis (p = 0.002). Those patients with a high (>=170 ng/mL) serum
      tissue inhibitor of metalloproteinase-1 level also had a poor prognosis (p <
      0.001), and the latter remained significant in multivariable analysis (hazard
      ratio = 1.85; 95% confidence interval: 1.26-2.72; p = 0.002). The molar ratio of
      serum matrix metalloproteinase-8 and tissue inhibitor of metalloproteinase-1
      levels with low (<0.07) or high (>0.30) molar ratios predicted a worse prognosis
      (p = 0.020). Tissue matrix metalloproteinase-8 did not influence prognosis. These
      results suggest that serum matrix metalloproteinase-8, tissue inhibitor of
      metalloproteinase-1, and the ratio of matrix metalloproteinase-8/ tissue
      inhibitor of metalloproteinase-1 may prove useful biomarkers for prediction of
      prognosis in patients with gastric cancer.

PMID- 30192206
TI  - Implementation Strategies for Telestroke: A Qualitative Study of Telestroke
      Networks in North Carolina.
AB  - BACKGROUND: Telestroke services allow under-resourced hospitals to gain access to
      stroke specialists to improve the timeliness and quality of stroke care. However,
      limited research is available on how telestroke networks are developed,
      implemented, and sustained. Understanding the process of telestroke network
      implementation is critical for developing implementation guidance and for
      evaluating determinants of implementation effectiveness. OBJECTIVE: This study
      examines the adoption decision process and strategies employed during telestroke
      network development, implementation, and sustainability. RESEARCH DESIGN: We
      interviewed representatives from five telestroke networks in North Carolina. Each
      network consisted of a distant site from which stroke consultation was provided
      and multiple originating sites at which the patient presented. SUBJECTS: The
      sample included 24 telestroke representatives (i.e., 5 network representatives
      and 19 hospital representatives) and 4 hospital representatives who do not
      participate in telestroke (i.e., nonadopters). MEASURES: The qualitative measures
      used in this study were based on Roger's stages of the innovation process in
      organizations. Stages included agenda setting and matching (pre-implementation),
      restructuring, redefining, and clarifying (implementation), and routinizing
      (sustainability). RESULTS: Distant and originating sites employed various
      strategies in the pre-implementation, implementation, and sustainability stages.
      Although there are many commonalities across networks, there are also important
      differences, for example in terms of network structure, quality monitoring, and
      performance feedback. Some nonadopter hospitals reported difficulty accessing
      information about telestroke, suggesting that some hospitals are not reached by
      telestroke network marketing efforts. CONCLUSIONS: Identifying and/or tailoring
      strategies to support the needs of hospitals in different telestroke network
      models should be a priority for future research.

PMID- 30192207
TI  - Evaluation of a Telehealth Counseling Program for Expatriates.
AB  - BACKGROUND: Health problems for expatriates are common due to their vulnerability
      to local infectious diseases, psychosocial problems, and chronic diseases, but
      many problems go largely unmet in this unique population. INTRODUCTION:
      Telehealth counseling was developed and tested for Korean expatriates. We
      explored the current status of using telehealth counseling systems and showed its
      feasibility and acceptability in three countries. MATERIALS AND METHODS: This
      retrospective study was based on the "Development and demonstration of telehealth
      counseling program for overseas Koreans" project funded by the Korea Health
      Industry Development Institute. In this project, we established five Digital
      Healthcare Centers (DHCs): 3 in Vietnam and 1 each in Uzbekistan and Cambodia. We
      used data from October 2016 to September 2017; descriptive analysis and one-way
      ANOVA were used to present detailed information. RESULTS: A total of 442 patients
      made an appointment for telehealth counseling services. Overall user satisfaction
      rates were 96.1%. Over two thirds of patients (302/442, 68.3%) completed one-time
      telehealth counseling. About 13% were referred to primary care, and 17 (3.8%)
      were referred to specialists or tertiary hospital. The most common diagnostic
      category was endocrine, nutritional, and metabolic diseases (14%), followed by
      diseases of the circulatory system (12.3%) for one-time visit patients.
      DISCUSSION: Our telehealth counseling program for expatriates was feasible and
      acceptable in three countries. It also has the potential to minimize language
      barriers and the cost of healthcare usage. CONCLUSION: Further research for
      sustainable effective telehealth systems for expatriates will be needed.

PMID- 30192210
TI  - Innovative Application of a Home-Based and Remote Sensing Cardiac Rehabilitation
      Protocol in Chinese Patients After Percutaneous Coronary Intervention.
AB  - BACKGROUND: Medical care for the Chinese population has been focused on first
      line activities, that is, therapy, but with little follow-up on treated patients.
      However, efficacy of therapy is highly dependent upon post-therapy recovery. For
      coronary heart disease (CHD), home-based cardiac telerehabilitation (HBCTR) is an
      alternative to hospital-based or center-based cardiac rehabilitation, and is an
      innovative approach to enhance recovery, but the approach is seldom used in
      China. Our preliminary survey in Shantou, China, indicated that most CHD patients
      showed a positive attitude toward the HBCTR technology. Our follow-up study was
      focused on assessing the effect of the HBCTR program in low-risk patients after
      percutaneous coronary intervention (PCI). MATERIALS AND METHODS: A two-arm
      randomized controlled trial was conducted at the First Affiliated Hospital of the
      Shantou University Medical College, China. The effectiveness of this program was
      measured by using blood pressure, Six-Minute Walking Test (6MWT), Fagerstrom Test
      for Nicotine Dependence (FTND), Cardiac Depression Scale (CDS), and SF-36 Health
      Survey (SF36). RESULTS: A total of 80 post-PCI patients were recruited and
      randomly divided into two equal groups. Based upon our effort, the usual care
      (UC) group received paper-based CHD educational booklets and biweekly outpatient
      review. The HBCTR group carried out outdoor walking/jogging exercise with real
      time physiological monitoring along with CHD education materials. After the 6
      week intervention, the 6MWT, SF36 (PCS, MCS), FTND and CDS in both groups were
      found to have significantly improved compared with baseline. In addition, the
      improvements in SF36, FTND scores, and 6MWT distance in the HBCTR group were
      significantly better than those in the UC group (p < 0.05). CONCLUSION: Our
      observations indicated that the HBCTR program may be applied successfully in
      Chinese patients who had very little technical skills and its application may be
      highly cost-effective.

PMID- 30192209
TI  - Patient Engagement and Cost Savings Achieved by Automated Telemonitoring Systems
      Designed to Prevent and Identify Surgical Site Infections After Joint
      Replacement.
AB  - BACKGROUND: We designed two telemonitoring text and voice messaging
      interventions, EpxDecolonization (EpxDecol) and EpxWound, to improve management
      of orthopedic joint replacement patients at Washington University. We reviewed
      the use of these tools for a period of 88 weeks. METHODS: Cohorts of 1,392 and
      1,753 participants completed EpxDecol and EpxWound, respectively. All patients
      who completed EpxDecol also completed EpxWound. We assessed patient use of and
      satisfaction with these interventions. A return on investment (ROI) analysis was
      conducted to determine the cost savings generated by EpxWound and EpxDecol.
      RESULTS: The proportions of patients who responded daily to EpxDecol and EpxWound
      were 91.9% and 77.7%, respectively, over the lengths of each intervention. The
      percent of daily responders declined <5% during each intervention. Ultimately,
      88.4% of EpxDecol patients and 67.8% of EpxWound patients responded to >=80% of
      all messages. Median patient survey responses (n = 1,246) were 9/9 (best
      possible) for care, 8/9 for improved communication, and 5/9 (perfect number) for
      number of messages received. ROI analysis for this 88-week period showed that
      using EpxDecol and EpxWound to engage patients (instead of nurses calling
      patients) saved the equivalent of 2.275 full-time nursing equivalents per week.
      We calculated net savings of $260,348 with an ROI of 14.85x for 1,753 patients
      over 88 weeks. One-year cost savings from these interventions were $153,800 with
      an ROI of 14.79x. CONCLUSIONS: EpxDecol and EpxWound may serve important roles in
      the perioperative process for orthopedic joint reconstruction surgery given high
      patient usage of and satisfaction with these interventions. Implementing EpxDecol
      and EpxWound for a large patient population could yield substantial cost savings
      and ROI.

PMID- 30192211
TI  - Healthcare Service Utilization under a New Virtual Primary Care Delivery Model.
AB  - BACKGROUND: Telemedicine holds great promise for changing healthcare delivery.
      While telemedicine has been used significantly in the direct-to-consumer setting,
      the use of telemedicine in a preventive primary care setting is not well studied.
      INTRODUCTION: ClickWell Care (CWC) is the first known implementation of a
      technology-enabled primary care model. We wanted to quantify healthcare
      utilization of primary care by patient characteristics and modality of care
      delivery. MATERIALS AND METHODS: Our study population included those who
      completed a visit to a CWC clinic between January 1, 2015 and September 30, 2015.
      We compared patients based on utilization of CWCs in-person and virtual visits
      across the following domains: patient demographics, distance from clinic,
      responses to a Health Risk Assessment, and top 10 conditions treated. RESULTS:
      Thousand two hundred seven patients completed a visit with a CWC physician in
      2015. Nearly three-quarters of our patients were <=40 years and sex was
      significantly different (p = 0.015) between visit cohorts. The greatest
      representation of men (47%) was seen in the virtual-only cohort. Patients'
      proximity to the clinic was also significantly different across visit cohorts (p
      = 0.018) with 44% of in-person-only and 34% of virtual-only patients living
      within 5 miles of Stanford Hospital. DISCUSSION: We found men were more likely to
      engage in virtual-only care. Young patients are willing to accept virtual care
      although many prefer to complete an in-person visit first. CONCLUSIONS: Our
      findings suggest that a "bricks-and-clicks" care model where telemedicine is
      supported by a brick-and-mortar location may be an effective way to leverage
      telemedicine to deliver primary care.

PMID- 30192212
TI  - Postoperative translation of the upper instrumented vertebra in thoracic
      adolescent idiopathic scoliosis.
AB  - OBJECTIVE The aim of this retrospective study was to analyze the influence of
      upper instrumented vertebra (UIV) translation from the C7 plumb line (C7PL) on
      the long-term postoperative results of patients with main thoracic (MT)
      adolescent idiopathic scoliosis (AIS). METHODS Twenty-five patients had been
      treated surgically for AIS with a Lenke type 1 curve and had been followed up for
      a mean period of 18.2 years. Radiographic parameters, pulmonary function
      measurements, and clinical outcomes were compared between the patients (n = 15)
      with UIV translation < 20 mm and those (n = 10) with UIV translation >= 20 mm at
      the final follow-up. Correlations between UIV translation and radiographic or
      pulmonary function parameters were analyzed. RESULTS Patients with >= 20 mm UIV
      translation at the final follow-up had a significantly larger preoperative UIV
      translation than that in the patients with < 20 mm UIV translation at follow-up.
      The former group also had a significantly lower correction rate of the MT curve,
      higher chest cage ratio, and lower radiographic shoulder height (p = 0.01, 0.005,
      and 0.025, respectively) at the final follow-up. The Scoliosis Research Society
      (SRS)-30 Questionnaire scores were equivalent between the two groups. Correlation
      analysis showed that the following parameters were significantly associated with
      UIV translation: MT curve correction rate (r = -0.481, p = 0.015), chest cage
      ratio (r = 0.673, p < 0.001), and percent-predicted forced expiratory volume in 1
      second (r = -0.455, p = 0.033). CONCLUSIONS The UIV translation should be
      considered an important factor that influences postoperative results. In MT AIS
      patients whose preoperative upper end vertebra (UEV) is distant from the C7PL,
      the UIV should be selected above the UEV to prevent large UIV translation at the
      postoperative follow-up.

PMID- 30192208
TI  - Clinically relevant radioresistant cells exhibit resistance to H2O2 by decreasing
      internal H2O2 and lipid peroxidation.
AB  - Radiation therapy is one of the choices to treat malignant tumors. In radiation
      therapy, existence of radiation-resistant cell is a major problem to overcome. We
      established clinically relevant radioresistant cells that had been obtained by
      exposing to 2 Gy/day X-rays for more than 30 days. These cells are resistant to 2
      Gy/day X-ray exposure and anticancer agents. However, the underlying resistance
      mechanism remains unclear. We investigated the resistance of clinically relevant
      radioresistant cells to hydrogen peroxide (H2O2), confirming a degree of
      resistance. Neither catalase enzyme activity nor aquaporins appeared to be
      involved in H2O2 resistance. Mitochondrial DNA copy number, adenosine
      triphosphate (ATP) concentration, and plasma membrane potential were decreased.
      The timing of H2O2 intake was delayed and lipid peroxidation was decreased.
      Sensitivity of clinically relevant radioresistant cells to H2O2 was enhanced by 1
      palmitoyl-2-(5'-oxo-valeroyl)-sn-glycero-3-phosphocholine administration. These
      results suggest that the membrane status is a major factor conferring H2O2
      resistance in clinically relevant radioresistant cells, and we should further
      investigate how membrane status could be used to enhance the therapeutic effect
      on cancer.

PMID- 30192213
TI  - Letter to the Editor. Reappraisal of nuchal ligament as a dura substitute for
      Chiari malformation type I.

PMID- 30192214
TI  - Letter to the Editor. Surgery for pediatric thalamic tumors: using DTI to improve
      neurological outcome.

PMID- 30192215
TI  - Tumor dissemination through surgical tracts in diffuse intrinsic pontine glioma.
AB  - OBJECTIVE Diffuse intrinsic pontine glioma (DIPG) is a highly aggressive and
      lethal brainstem tumor in children. In the 1980s, routine biopsy at presentation
      was abandoned since it was claimed "unnecessary" for diagnosis. In the last
      decade, however, several groups have reincorporated this procedure as standard of
      care or in the context of clinical trials. Expert neurosurgical teams report no
      mortality and acceptable morbidity, and no relevant complications have been
      previously described. The aim of this study was to review needle tract
      dissemination as a potential complication in DIPG. METHODS The authors
      retrospectively analyzed the incidence of dissemination through surgical tracts
      in DIPG patients who underwent biopsy procedures at diagnosis in 3 dedicated
      centers. Clinical records and images as well as radiation dosimetry from
      diagnosis to relapse were reviewed. RESULTS Four patients (2 boys and 2 girls,
      age range 6-12 years) had surgical tract dissemination: in 3 cases in the needle
      tract and in 1 case in the Ommaya catheter tract. The median time from biopsy to
      identification of dissemination was 5 months (range 4-6 months). The median
      overall survival was 11 months (range 7-12 months). Disseminated lesions were in
      the marginal radiotherapy field (n = 2), out of the field (n = 1), and in the
      radiotherapy field (n = 1). CONCLUSIONS Although surgical tract dissemination in
      DIPG is a rare complication (associated with 2.4% of procedures in this study),
      it should be mentioned to patients and family when procedures involving a
      surgical tract are proposed. The inclusion of the needle tract in the
      radiotherapy field may have only limited benefit. Future studies are warranted to
      explore the benefit of larger radiotherapy fields in patients with DIPG.

PMID- 30192217
TI  - Letter to the Editor. Considerations about the use of negative-pressure dressing
      therapy after spine surgery.

PMID- 30192216
TI  - The full-endoscopic uniportal technique for decompression of the anterior
      craniocervical junction using the retropharyngeal approach: an anatomical
      feasibility study in human cadavers and review of the literature.
AB  - OBJECTIVE Acute or progressive myelopathy may necessitate direct anterior
      decompression of the craniocervical junction and odontoidectomy. Different
      techniques with individual advantages and disadvantages can be used. In addition
      to the gold standard-the transoral approach-there is also increasing experience
      with the endoscopic transnasal technique. Other alternative methods are also
      being developed to reduce technical and perioperative problems. The aim of this
      anatomical study was to investigate the feasibility of the full-endoscopic
      uniportal technique with a retropharyngeal approach for decompression of the
      craniocervical junction, taking into consideration the specific advantages and
      disadvantages compared with conventional methods and the currently available data
      in the literature. METHODS Five fresh adult cadavers were operated on. The
      endoscope used has a shaft cross-section of 6.9 * 5.9 mm and a 25 degrees 
      viewing angle. It contains an eccentric intraendoscopic working channel with a
      diameter of 4.1 mm. An anterior retropharyngeal approach was used. The anatomical
      structures of the anterior craniocervical junction were dissected and the
      bulbomedullary junction was decompressed. RESULTS The planned steps of the
      operation were performed in all cadavers. The retropharyngeal approach allowed
      the target region to be accessed easily. The anatomical structures of the
      anterior craniocervical junction could be identified and dissected. The
      bulbomedullary junction could be adequately decompressed. No resections of the
      anterior arch of the atlas were necessary in the odontoidectomy. CONCLUSIONS
      Using the full-endoscopic uniportal technique with an anterior retropharyngeal
      approach, the craniocervical region can be adequately reached, dissected, and
      decompressed. This is a minimally invasive technique with the known advantages of
      an endoscopic procedure under continuous irrigation. The retropharyngeal approach
      allows direct, sterile access. The instruments are available for clinical use and
      have been established for years in other operations of the entire spine.

PMID- 30192218
TI  - Traumatic lumbar spondylolisthesis resulting in complete thoracic spinal cord
      avulsion: an unusual presentation.
AB  - Traumatic spondylolisthesis is a known occurrence in trauma, but complete cord
      transection is relatively rare. Moreover, complete cord transection at a site
      distant from the traumatic spondylolisthesis without spondyloptosis is
      exceedingly rare. In this report, authors describe the first case of thoracic
      cord avulsion following a traumatic grade II lumbar spondylolisthesis. The
      unusual presentation of this case highlights the importance of further evaluating
      patients with neurological symptoms out of proportion with the injuries seen on
      initial imaging. Magnetic resonance imaging performed after initial imaging
      studies demonstrated T11 cord transection with the distal cord herniating into
      the lumbar paraspinal soft tissues, thus allowing for preoperative planning to
      prepare for a more significant intervention including complex dural repair and
      lumbar drain placement, in addition to instrumented fusion to stabilize the
      traumatic spondylolisthesis.

PMID- 30192219
TI  - Direct puncture for diagnosis of intradural spinal arachnoid cyst and
      fenestration using 3D rotational fluoroscopy: technical note and the "jellyfish
      sign".
AB  - The authors report on a 47-year-old woman with a symptomatic thoracic spinal
      arachnoid cyst (SAC) who underwent a novel procedure that involves direct
      puncture of the SAC to visualize, diagnose, and potentially treat these rare
      spinal lesions. The method described utilizes 3D fluoroscopy to gain access to
      the SAC, followed by injection of myelographic contrast into the cyst. A
      characteristic "jellyfish sign" was observed that represents the containment of
      the contrast within the superior aspect of the cyst and a clear block of cranial
      flow of contrast, resulting in an undulating pattern of movement of contrast
      within the cyst. Following balloon fenestration of the cyst, unimpeded flow of
      contrast was visualized cranially throughout the thoracic subarachnoid space. The
      patient was discharged the following day in good condition, and subsequently
      experienced 1 year free from symptoms. This is the first reported case of a
      successful direct puncture of an SAC with balloon fenestration, and the first
      noted real-time fluoroscopic "behavior" of CSF within an arachnoid cyst.

PMID- 30192220
TI  - Biomechanical study of injectable hollow pedicle screws for PMMA augmentation in
      severely osteoporotic lumbar vertebrae: effect of PMMA distribution and volume on
      screw stability.
AB  - OBJECTIVE The purpose of this study was to compare stability of injectable hollow
      pedicle screws with different numbers of holes using different volumes of
      polymethylmethacrylate (PMMA) in severely osteoporotic lumbar vertebrae and
      analyze the relationship between screw stability and distribution and volume of
      PMMA. METHODS Forty-eight severely osteoporotic cadaveric lumbar vertebrae were
      randomly divided into 3 groups-groups A, B, and C (16 vertebrae per group). The
      screws used in group A had 4 holes (2 pairs of holes, with the second hole of
      each pair placed 180 degrees  further along the thread than the first). The
      screws used in group B had 6 holes (3 pairs of holes, placed with the same 180
      degrees  difference in position). Unmodified conventional screws were used in
      group C. Each group was randomly divided into subgroups 0, 1, 2, and 3, with
      different volumes of PMMA used in each subgroup. Type A and B pedicle screws were
      directly inserted into the vertebrae in groups A and B, respectively, and then
      different volumes of PMMA were injected through the screws into the vertebrae in
      subgroups 0, 1, 2, and 3. The pilot hole was filled with different volumes of
      PMMA followed by insertion of screws in groups C0, C1, C2, and C3. Distributions
      of PMMA were evaluated radiographically, and axial pull-out tests were performed
      to measure the maximum axial pullout strength (Fmax). RESULTS Radiographic
      examination revealed that PMMA surrounded the anterior third of the screws in the
      vertebral bodies (VBs) in groups A1, A2, and A3; the middle third of screws in
      the junction area of the vertebral body (VB) and pedicle in groups B1, B2, and
      B3; and the full length of screws evenly in both VB and pedicle in groups C1, C2,
      and C3. In addition, in groups A3 and B3, PMMA from each of the screws (left and
      right) was in contact with PMMA from the other screw and the PMMA was closer to
      the posterior wall and pedicle than in groups A1, A2, B1, and B2. One instance of
      PMMA leakage was found (in group B3). Two-way analysis of variance revealed that
      2 factors-distribution and volume of PMMA-significantly influenced Fmax (p <
      0.05) but that they were not significantly correlated (p = 0.078). The Fmax
      values in groups in which screws were augmented with PMMA were significantly
      better than those in groups in which no PMMA was used (p < 0.05). CONCLUSIONS
      PMMA can significantly improve stability of different injectable pedicle screws
      in severely osteoporotic lumbar vertebrae, and screw stability is significantly
      correlated with distribution and volume of PMMA. The closer the PMMA is to the
      pedicle and the greater the quantity of injected PMMA used, the greater the
      pedicle screw stability is. Injection of 3.0 mL PMMA through screws with 4 holes
      (2 pair of holes, with the screws in each pair placed on opposite sides of the
      screw) produces optimal stability in severely osteoporotic lumbar vertebrae.

PMID- 30192221
TI  - Thoracogenic spinal deformity: a rare cause of early-onset scoliosis.
AB  - OBJECTIVE Surgery for severe congenital defects, such as congenital diaphragmatic
      hernia, congenital heart defects, and tracheoesophageal disorders, are life
      saving treatments for many infants. However, the incidence of scoliosis following
      thoracoabdominal surgery has been reported to range from 8% to 50%. Little is
      known about severe scoliosis that occurs after chest wall procedures in infants.
      The authors sought to determine the prevalence of thoracogenic scoliosis, disease
      severity, and need for scoliosis surgery in patients who underwent chest wall
      procedures in early childhood. METHODS A multicenter database of patients with
      early-onset scoliosis was queried to identify patients with a history of
      thoracogenic or acquired iatrogenic scoliosis. Patients with significant
      congenital spine deformities were excluded. Forty-one patients (1.6%) were noted
      to have thoracogenic scoliosis. Of these patients, 14 patients were observed; 10
      received casts and/or braces; and 17 underwent treatment with rib-based
      distraction rods, Shilla procedures, or spine-based growing rod devices.
      Radiographs, complications, and patient characteristics were reviewed. RESULTS
      The mean age at scoliosis diagnosis for the 41 patients was 6.0 years. The mean
      time to follow-up was 2.9 years (4.5 years in the 17 surgical patients). The mean
      preoperative coronal Cobb angle in the surgical group was 65 degrees  and
      improved to 47 degrees  postoperatively (p = 0.01). The mean Cobb angle for the
      nonoperative group was 31 degrees  initially and 32 degrees  at follow-up (p =
      0.44). Among the 17 patients undergoing surgery for scoliosis, there were 13
      complications in 7 patients, including a brachial plexus palsy following rib
      based distraction rod placement. This resolved with revision of the rib hooks.
      There were no known complications in the nonoperative cohort. CONCLUSIONS Severe
      scoliosis can develop after thoracoabdominal surgeries during infancy. Further
      work is needed to understand the pathogenesis of scoliosis in this population so
      as to implement measures for prevention and early diagnosis and to guide
      appropriate treatment.

PMID- 30192222
TI  - International Committee on Systematics of Prokaryotes Subcommittee on the
      taxonomy of rhizobia and agrobacteria Minutes of the closed meeting, Granada, 4
      September 2017.

PMID- 30192223
TI  - International Committee on Systematics of Prokaryotes Subcommittee on the
      taxonomy of Chlamydiae. Minutes of the closed meeting, 9 April 2017, Charlotte,
      USA.

PMID- 30192224
TI  - Paradiplozoon yunnanensis n. sp. (Monogenea, Diplozoidae) from Sikukia gudgeri
      (Cyprinidae, Barbinae) in southwest China.
AB  - Paradiplozoon yunnanensis n. sp. (Monogenea, Diplozoidae) is described from the
      gills of Sikukia gudgeri Smith, 1931 (Cyprinidae) collected from Jinghong Basin,
      a tributary of the international Lancang-Mekong River. This is the first
      diplozoid species from S. gudgeri and its description increases the number of
      Paradiplozoon species recorded in China to 25. The new species is distinguished
      from congeners by a combination of morphological and molecular features. The
      anterior end of the median plate is thickened in the marginal area and a narrow
      rectangular trapeze spur connects to the anterior jaw through two separate
      anterior joining sclerites. The posterior end of the median plate sclerite is
      invaginated with a smooth strip-shaped posterior joining sclerite. Comparison of
      a newly obtained sequence of rRNA ITS2 with 18 other congeneric sequences from
      GenBank provides support for separation of the new species.

PMID- 30192225
TI  - Biomechanical evaluation of annulus fibrosus repair with scaffold and soft
      anchors in an ex vivo porcine model.
AB  - INTRODUCTION: Altered biomechanical properties, due to intervertebral disc (IVD)
      degeneration and missing nucleus fibrosus, could be thought as one of the reasons
      for the back pain many herniation patients experience after surgery. It has been
      suggested to repair annulus fibrosus (AF) to restore stability and allow nucleus
      pulposus (NP) replacement and furthermore prevent reherniation. The aim of this
      study was to evaluate a new method for closing a defect in AF for use in
      herniation surgery. METHODS: Our repair method combines a polycaprolactone (PCL)
      scaffold plugging herniation and soft anchors to secure the plug. Ex vivo
      biomechanical testing was carried out in nine porcine lumbar motion segments.
      Flexion-extension, lateral bending and rotation were repeated three times: first
      in healthy specimens, second with a full thickness circular defect applied, and
      third time with the specimens repaired. Finally push out tests were performed to
      check whether the plug would remain in. RESULTS: Tests showed that applying a
      defect to the AF increases the range of motion (ROM), neutral zone (NZ) and
      neutral zone stiffness (NZS). In flexion/extension it was found significant for
      ROM, NZ, and NZS. For lateral bending and rotation a significant increase in ROM
      occurred. After AF repair ROM, NZ and NZS were normalized. All plugs remained in
      the AF during push out test up until 4000 N, but NP was squeezed out through the
      pores of the scaffold. DISCUSSION: A defect in the AF changes the biomechanical
      properties in the motion segment, changes that point to instability. Repairing
      the defect with a PCL plug and soft anchors brought the biomechanical behavior
      back to native state. This concept is promising and might be a viable way to
      repair the IVD after surgery.

PMID- 30192226
TI  - Sequential management of tibial fractures using a temporary unicortical external
      fixator.
AB  - INTRODUCTION: The development of damage control orthopedics (DCO) procedures has
      led to the development of temporary unicortical external fixators (TUEFs)
      intended to limit deep infectious complications and facilitate early conversion
      to internal fixation. METHODS: A retrospective study was conducted in two French
      military trauma centers, including on patients being treated for tibial fractures
      with a TUEF (UNYCO(r) - Orthofix(r)) followed by an early conversion to
      intramedullary nailing. RESULTS: Eleven patients with an average age of 41 were
      included between September 2015 and June 2017. A total of 12 TUEFs were implanted
      for one closed fracture and 11 open fractures, including one type I, eight types
      II, and two Gustilo types IIIB. The indication of DCO was related to hemodynamic
      instability in three cases, to the severity of soft tissue lesions in eight
      cases, and to the context of treatment in one case. The conversion to IM nailing
      was made after an average of 7.6 days. No significant loss of reduction was
      observed until internal osteosynthesis, which was performed with "fixator in
      place" in ten cases. The coverage of Gustilo type III injuries was performed by
      free flap transfers at the same time as IM nailing. All the patients were
      reviewed with an average follow-up of 16.5 months. Bone union was achieved in all
      cases. Two IM nailing dynamizations were carried out, but no bone grafting was
      required. Two cases of pandiaphysitis were observed and treated without
      functional complications. DISCUSSION: Despite a limited number of patients, this
      study demonstrates the reliability of the TUEF to maintain the reduction of
      tibial fractures and facilitate early conversion to IM nailing. Unicortical
      fixation does not prevent septic complications related to the severity of soft
      tissue injuries.

PMID- 30192227
TI  - Non-invasive measurement of mRNA decay reveals translation initiation as the
      major determinant of mRNA stability.
AB  - The cytoplasmic abundance of mRNAs is strictly controlled through a balance of
      production and degradation. Whereas the control of mRNA synthesis through
      transcription has been well characterized, less is known about the regulation of
      mRNA turnover, and a consensus model explaining the wide variations in mRNA decay
      rates remains elusive. Here, we combine non-invasive transcriptome-wide mRNA
      production and stability measurements with selective and acute perturbations to
      demonstrate that mRNA degradation is tightly coupled to the regulation of
      translation, and that a competition between translation initiation and mRNA decay
      -but not codon optimality or elongation- is the major determinant of mRNA
      stability in yeast. Our refined measurements also reveal a remarkably dynamic
      transcriptome with an average mRNA half-life of only 4.8 min - much shorter than
      previously thought. Furthermore, global mRNA destabilization by inhibition of
      translation initiation induces a dose-dependent formation of processing bodies in
      which mRNAs can decay over time.

PMID- 30192228
TI  - Defective RNA polymerase III is negatively regulated by the SUMO-Ubiquitin-Cdc48
      pathway.
AB  - Transcription by RNA polymerase III (Pol III) is an essential cellular process,
      and mutations in Pol III can cause neurodegenerative disease in humans. However,
      in contrast to Pol II transcription, which has been extensively studied, the
      knowledge of how Pol III is regulated is very limited. We report here that in
      budding yeast, Saccharomyces cerevisiae, Pol III is negatively regulated by the
      Small Ubiquitin-like MOdifier (SUMO), an essential post-translational
      modification pathway. Besides sumoylation, Pol III is also targeted by
      ubiquitylation and the Cdc48/p97 segregase; these three processes likely act in a
      sequential manner and eventually lead to proteasomal degradation of Pol III
      subunits, thereby repressing Pol III transcription. This study not only uncovered
      a regulatory mechanism for Pol III, but also suggests that the SUMO and ubiquitin
      modification pathways and the Cdc48/p97 segregase can be potential therapeutic
      targets for Pol III-related human diseases.

PMID- 30192231
TI  - Effectiveness of 8 weeks of ledipasvir/sofosbuvir for hepatitis C in HCV-HIV
      coinfected patients.
AB  - BACKGROUND: Data is limited on the use of 8 weeks of therapy with
      Ledipasvir/Sofosbuvir (LDV/SOF) for special populations such as HCV/HIV
      coinfected patients. The primary objective of this analysis was to compare SVR12
      rates among HCV-monoinfected and HCV/HIV-coinfected patients in a real-world
      clinical setting. Additionally, we compared SVR12 rates among patients receiving
      8 versus 12 weeks of therapy. METHODS: This was a single-center, retrospective
      study of HCV-infected patients prescribed LDV/SOF at ambulatory clinics
      associated with the University of Maryland Medical Center (UMMC) from May 2015 to
      May 2016. Data were obtained from UMMC electronic medical record and outpatient
      pharmacy claims database. Comparisons between groups were made using Chi-squared
      or Fisher's exact test for categorical variables and Student's t-test or Wilcoxon
      rank-sum for continuous variables. All analyses were per-protocol; patients
      missing SVR12 data (25.2%) could not be evaluated for our stated objectives.
      RESULTS: A total of 274 patients were included. Median age was 58 years; 62.8%
      were male; 82.5% were black. SVR12 data was available for 65 HCV/HIV-coinfected
      patients, of which 62 (95.4%) achieved SVR12. There was no difference in SVR12
      rate between HCV/HIV-coinfected patients and HCV-monoinfected patients (86/90;
      95.6%) (p = 0.959). Additionally, there was no difference in SVR12 attainment
      between HIV/HCV-coinfected patients who received 8 versus 12 weeks of therapy (p
      = 0.101). CONCLUSIONS: Eight weeks of LDV/SOF was effective for treatment-naive,
      non-cirrhotic, HCV-genotype 1 patients in this real-world setting, regardless of
      HIV status. Increased uptake of the 8-week regimen can decrease costs for
      patients and payers without compromising outcomes.

PMID- 30192232
TI  - Estimation of the infinitesimal generator by square-root approximation.
AB  - In recent years, for the analysis of molecular processes, the estimation of time
      scales and transition rates has become fundamental. Estimating the transition
      rates between molecular conformations is-from a mathematical point of view-an
      invariant subspace projection problem. We present a method to project the
      infinitesimal generator acting on function space to a low-dimensional rate
      matrix. This projection can be performed in two steps. First, we discretize the
      conformational space in a Voronoi tessellation, then the transition rates between
      adjacent cells is approximated by the geometric average of the Boltzmann weights
      of the Voronoi cells. This method demonstrates that there is a direct relation
      between the potential energy surface of molecular structures and the transition
      rates of conformational changes. We will show also that this approximation is
      correct and converges to the generator of the Smoluchowski equation in the limit
      of infinitely small Voronoi cells. We present results for a two dimensional
      diffusion process and alanine dipeptide as a high-dimensional system.

PMID- 30192229
TI  - BDNF-TrkB signaling in oxytocin neurons contributes to maternal behavior.
AB  - Brain-derived neurotrophic factor (Bdnf) transcription is controlled by several
      promoters, which drive expression of multiple transcripts encoding an identical
      protein. We previously reported that BDNF derived from promoters I and II is
      highly expressed in hypothalamus and is critical for regulating aggression in
      male mice. Here we report that BDNF loss from these promoters causes reduced
      sexual receptivity and impaired maternal care in female mice, which is
      concomitant with decreased oxytocin (Oxt) expression during development. We
      identify a novel link between BDNF signaling, oxytocin, and maternal behavior by
      demonstrating that ablation of TrkB selectively in OXT neurons partially
      recapitulates maternal care impairments observed in BDNF-deficient females. Using
      translating ribosome affinity purification and RNA-sequencing we define a
      molecular profile for OXT neurons and delineate how BDNF signaling impacts gene
      pathways critical for structural and functional plasticity. Our findings
      highlight BDNF as a modulator of sexually-dimorphic hypothalamic circuits that
      govern female-typical behaviors.

PMID- 30192233
TI  - Formation of n- and p-type regions in individual Si/SiO2 core/shell nanowires by
      ion beam doping.
AB  - A method for cross-sectional doping of individual Si/SiO2 core/shell nanowires
      (NWs) is presented. P and B atoms are laterally implanted at different depths in
      the Si core. The healing of the implantation-related damage together with the
      electrical activation of the dopants takes place via solid phase epitaxy driven
      by millisecond-range flash lamp annealing. Electrical measurements through a
      bevel formed along the NW enabled us to demonstrate the concurrent formation of n
      and p-type regions in individual Si/SiO2 core/shell NWs. These results might
      pave the way for ion beam doping of nanostructured semiconductors produced by
      using either top-down or bottom-up approaches.

PMID- 30192234
TI  - Dielectric properties of ferroelectric nanocomposites: effects of thermal
      stresses and filler shape anisotropy.
AB  - Ferroelectric nanocomposites are intriguing nonhomogeneous materials, which may
      have unusual phase states and specific physical properties useful for practical
      applications. Here we theoretically describe dielectric properties of
      nanocomposites comprising single-domain ferroelectric nanocrystals embedded into
      a linear dielectric medium. First, small-signal intrinsic permittivities of
      spheroidal PbTiO3 and BaTiO3 crystallites surrounded by an isotropic matrix with
      linear elastic properties are calculated with the aid of a nonlinear
      thermodynamic theory. It is shown that thermal stresses caused by differences in
      thermal expansion between the inclusions and the matrix may strongly influence
      the intrinsic permittivities of ferroelectric nanocrystals. Second, macroscopic
      dielectric responses of ferroelectric-dielectric composites are evaluated in the
      Maxwell Garnett approximation. For effective permittivities of such composites,
      generalized relations are derived, which allow for both the shape and dielectric
      anisotropies of ferroelectric nanocrystals. Numerical calculations of the
      effective permittivities are performed for composites comprising PbTiO3 and
      BaTiO3 nanocrystals embedded into representative dielectric matrices generating
      tensile (silica glass) or compressive (potassium silicate glass) thermal stresses
      inside ferroelectric inclusions. For nanocomposites involving randomly oriented
      and similarly aligned spheroidal inclusions, temperature dependences of the
      effective permittivities are determined with the account of phase transitions
      occurring in strained ferroelectric nanocrystals and suppression of their
      dielectric responses due to the depolarizing-field effect created by low
      permittivity matrix. Our theoretical calculations show that effective
      permittivities of composites comprising needle-like or disc-shaped ferroelectric
      inclusions could strongly exceed the permittivity of the matrix. Most
      importantly, we predict that BaTiO3-K2O-SiO2 composites with such inclusions
      should exhibit a broad dielectric peak around the room temperature, which is
      associated with shifted structural transitions in strained BaTiO3 nanocrystals.
      The presented theory provides guidelines for the development of ferroelectric
      nanocomposites with enhanced dielectric responses, which could be suitable for
      applications in supercapacitors and other advanced electronic devices.

PMID- 30192230
TI  - tp53 deficiency causes a wide tumor spectrum and increases embryonal
      rhabdomyosarcoma metastasis in zebrafish.
AB  - The TP53 tumor-suppressor gene is mutated in >50% of human tumors and Li-Fraumeni
      patients with germ line inactivation are predisposed to developing cancer. Here,
      we generated tp53 deleted zebrafish that spontaneously develop malignant
      peripheral nerve-sheath tumors, angiosarcomas, germ cell tumors, and an
      aggressive Natural Killer cell-like leukemia for which no animal model has been
      developed. Because the tp53 deletion was generated in syngeneic zebrafish,
      engraftment of fluorescent-labeled tumors could be dynamically visualized over
      time. Importantly, engrafted tumors shared gene expression signatures with
      predicted cells of origin in human tissue. Finally, we showed that tp53del/del
      enhanced invasion and metastasis in kRASG12D-induced embryonal rhabdomyosarcoma
      (ERMS), but did not alter the overall frequency of cancer stem cells, suggesting
      novel pro-metastatic roles for TP53 loss-of-function in human muscle tumors. In
      summary, we have developed a Li-Fraumeni zebrafish model that is amenable to
      large-scale transplantation and direct visualization of tumor growth in live
      animals.

PMID- 30192235
TI  - Wave intensity analysis in the internal carotid artery of hypertensive subjects
      using phase-contrast MR angiography and preliminary assessment of the effect of
      vessel morphology on wave dynamics.
AB  - OBJECTIVE: Hypertension is associated with reduced cerebral blood flow, but it is
      not known how this impacts on wave dynamics or potentially relates to arterial
      morphology. Given the location of the internal carotid artery (ICA) and risks
      associated with invasive measurements, wave dynamics in this artery have not been
      extensively assessed in vivo. This study explores the feasibility of studying
      wave dynamics in the internal carotid artery non-invasively. APPROACH:
      Normotensive, uncontrolled and controlled hypertensive participants were
      recruited (daytime ambulatory blood pressure  <135/85 mmHg and  >135/85 mmHg,
      respectively; n  =  38). Wave intensity, reservoir pressure and statistical shape
      analyses were performed on the right ICA and ascending aorta high-resolution
      phase-contrast magnetic resonance angiography data. MAIN RESULTS: Wave speed in
      the aorta was significantly lower in normotensive compared to hypertensive
      participants (6.7  +/-  1.8 versus 11.2  +/-  6.2 m s-1 for uncontrolled and 11.8
      +/-  4.6 m s-1 for controlled hypertensives, p  =  0.02), whilst there were no
      differences in wave speed in the ICA. There were no significant differences
      between the groups for the wave intensity or reservoir pressure. Interestingly, a
      significant association between the anatomy of the ICA and wave energy (FCW and
      size, r 2  =  0.12, p  =  0.04) was found. SIGNIFICANCE: This study shows it is
      feasible to study wave dynamics in the ICA non-invasively. Whilst changes in
      aortic wave speed confirmed an expected increase in arterial stiffness, this was
      not observed in the ICA. This might suggest a protective mechanism in the
      cerebral circulation, in conjunction with the effect of vessel tortuosity.
      Furthermore, it was observed that ICA shape correlated with wave energy but not
      wave speed.

PMID- 30192236
TI  - Intrinsically absorbing photoacoustic and ultrasound contrast agents for cancer
      therapy and imaging.
AB  - Nanoparticles are submicrometer in size and are used in a variety of ways in the
      biomedical field. They can carry therapeutic drugs, either in the particle core
      or surface to target cancer sites in the body. Additionally they can contain
      imaging agents to diagnose and monitor the tumor size using different imaging
      modalities, such as fluorescence and nuclear magnetic resonance imaging. Novel
      theranostic nanoparticle agents, called perfluorohexane nanoemulsions (PFH-NEs)
      were synthesized whose intrinsic properties could be used for both imaging
      (ultrasound and photoacoustic) and therapy. Compared to other theranostic agents,
      our PFH-NEs can absorb sufficient near-infrared light to enhance contrast and
      provide deeper penetration imaging at laser fluences causing minimal damage to
      healthy tissue. One contrast mechanism (optical absorption/photoacoustics) allows
      us to validate localization of the agent and another (acoustic
      impedance/ultrasound) allows the imaging of therapeutic delivery after particle
      activation. In this work, we show the potential of these PFH-NEs to be used as
      multimodal imaging agents and for therapy.

PMID- 30192237
TI  - Nanohybrid structured RuO2/Mn2O3/CNF as a catalyst for Na-O2 batteries.
AB  - A 3D RuO2/Mn2O3/carbon nanofiber (CNF) composite has been prepared in this study
      by a facile two step microwave synthesis, as a bi-functional electrocatalyst
      towards oxygen reduction reaction (ORR) and oxygen evolution reaction (OER). RuO2
      nanoparticles with the mean size of 1.57 nm are uniformly distributed on Mn2O3
      nano-rods grown on electrospun CNFs. The electrocatalytic activity of the
      composites are investigated towards ORR/OER under alkaline condition. The ternary
      RuO2/Mn2O3/CNF composite showed superior ORR activity in terms of onset potential
      (0.95 V versus RHE) and Tafel slope (121 mV dec-1) compared to its RuO2/CNF and
      Mn2O3/CNF counterparts. In the case of OER, the RuO2/Mn2O3/CNF exhibited 0.34 V
      over-potential value measured at 10 mA cm-2 and 52 mV dec-1 Tafel slope which are
      lower than those of the other synthesized samples and as compared to state of the
      art RuO2 and IrO x type materials. RuO2/Mn2O3/CNF also exhibited higher specific
      capacity (9352 mAh [Formula: see text]) than CNF (1395 mAh [Formula: see text]),
      Mn2O3/CNF (3108 mAh [Formula: see text]) and RuO2/CNF (4859 mAh g carbon -1) as
      the cathode material in Na-O2 battery, which indicates the validity of the
      results in non-aqueous medium. Taking the benefit of RuO2 and Mn2O3 synergistic
      effect, the decomposition of inevitable side products at the end of charge occurs
      at 3.838 V versus Na/Na+ by using RuO2/Mn2O3/CNF, which is 388 mV more cathodic
      compared with CNF.

PMID- 30192238
TI  - Evolving Use of Biomarkers in the Management of Heart Failure.
AB  - Objective, noninvasive, clinical assessment of patients with heart failure can be
      made using biomarker measurements, including natriuretic peptides, cardiac
      troponins, soluble suppression of tumorigenicity-2, and galectin-3. The aim of
      this review is to provide clinicians with guidance on the use of heart failure
      biomarkers in clinical practice. The authors provide a didactic narrative based
      on current literature, an exemplary case study, and their clinical
      experience.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- 30192239
TI  - Double-chambered Right Ventricle.

PMID- 30192240
TI  - Preoperative Cardiac Evaluation before Noncardiac Surgery: Reverend Bayes's Risk
      Indices and Optimal Variables.

PMID- 30192241
TI  - Blue Rubber Bleb Nevus Syndrome.

PMID- 30192242
TI  - Repair of a Giant Ascending Aortic Pseudoaneurysm Requiring Awake Institution of
      Cardiopulmonary Bypass.

PMID- 30192244
TI  - Physical Therapy After Lumbar Spinal Fusion is Necessary to Optimize Patient
      Outcomes.

PMID- 30192243
TI  - Patterns of Immunohistochemistry Utilization in Metastases to the Liver.
AB  - Immunohistochemistry (IHC) is a well-established morphology adjunct enabling
      pathologists to make accurate diagnoses. Metastases to the liver is a common
      scenario where pathologists may rely heavily on IHC in their interpretation. We
      conducted this study to audit the patterns of IHC utilization in malignant liver
      biopsies in 3 practice types (academic, community, and expert) as an initial step
      toward developing best practice guidelines. A total of 1100 specimens were
      analyzed and the association between the availability of history of other
      malignancies and the practice type on IHC utilization was studied. Community
      pathologists were twice as likely to use IHC and to use more markers per case
      than academic pathologists or the expert pathologist. When history of another
      malignancy was available, pathologists were not only 1.5 times more likely to use
      IHC but they also used more markers per case. IHC was still deemed necessary to
      reach the diagnosis in 67% of cases with a given history of other malignancy.
      This study described several variables for consideration in our effort to develop
      IHC utilization guidelines and its results quantify the variance noted among
      practice types.

PMID- 30192246
TI  - Not throwing away my shot.

PMID- 30192245
TI  - Investing in workability of patients with inflammatory bowel disease: results of
      a pilot project Activ84worK (Activate for work).
AB  - OBJECTIVES: Inflammatory bowel diseases (IBD) are chronic gastrointestinal
      conditions mainly affecting young people. Disease symptoms often make it
      difficult to actively participate in the workplace. The aim of Activ84worK was to
      stimulate professional activity and reduce absenteeism by removing work-related
      stress factors and providing patients with more flexible working conditions.
      PATIENTS AND METHODS: Activ84worK was a collaboration between Abbvie, Mensura,
      Proximus, SD Worx, and University Hospitals Leuven (UZ Leuven) with the support
      of the patient association 'Crohn-en Colitis Ulcerosa Vereniging (CCV vzw)' in
      Flanders, Belgium. Since March 2015, IBD patients whose employer was also willing
      to participate, were recruited. Informed consent was signed and both the employee
      and the employer were followed for 6 months. RESULTS: Between March 2015 and
      October 2016, 70 patients showed interest in the Activ84worK program, 18 were
      eligible to participate, and 14 completed the program (29% male, 29% private
      companies). The case studies, based on interviews conducted with participating
      employees, indicated that removing work-related stress factors resulted in
      employees feeling much more at ease. Concretely, this led to absence of sick
      leave for more than 50% of the included patients. A higher degree of workability
      and focus of employees was achieved, and a decrease in costs of absenteeism was
      associated with this. CONCLUSION: This pilot project shows that teleworking and
      flexible working conditions improve labor participation of IBD patients. The
      results of this project are now used to inspire policy-makers and employers. This
      initiative should be extended to a larger cohort and tested in other chronic
      diseases.

PMID- 30192247
TI  - Preoperative Narcotic Use and Inferior Outcomes After Anatomic Total Shoulder
      Arthroplasty: A Clinical and Radiographic Analysis.
AB  - INTRODUCTION: Our purpose was to determine whether the chronic use of
      preoperative narcotics adversely affected clinical and/or radiographic outcomes.
      METHODS: Seventy-three patients (79 shoulders) with primary total shoulder
      arthroplasty for osteoarthritis were evaluated clinically and radiographically at
      preoperative visits and postoperatively at a minimum follow-up of 2 years: 26
      patients (28 shoulders) taking chronic narcotic pain medication for at least 3
      months before surgery and 47 patients (51 shoulders) who were not taking
      narcotics preoperatively. RESULTS: Postoperatively, significant differences were
      noted between the narcotic and nonnarcotic groups regarding American Shoulder and
      Elbow Surgeons scores and visual analog scale scores, as well as forward
      elevation, external rotation, and all strength measurements (P < 0.01). The
      nonnarcotic group had markedly higher American Shoulder and Elbow Surgeons
      scores, better overall range of motion and strength, and markedly lower visual
      analog scale scores than the narcotic group. CONCLUSION: Chronic preoperative
      narcotic use seems to be a notable indicator of poor outcomes of anatomic total
      shoulder arthroplasty for glenohumeral osteoarthritis.

PMID- 30192248
TI  - Cost Comparison of Surgically Treated Ankle Fractures Managed in an Inpatient
      Versus Outpatient Setting.
AB  - INTRODUCTION: Although choices physicians make profoundly affect the cost of
      health care, few surgeons know relative costs associated with the setting in
      which care is provided. Without valid cost information, surgeons cannot
      understand how their choices affect the total cost of care. METHODS: Actual costs
      for all isolated, surgically treated ankle fractures at a level I trauma hospital
      and affiliated outpatient surgery center were determined using a validated
      episode of care costing system and analyzed using multivariate regression
      analysis in this retrospective cohort study. RESULTS: One hundred forty-eight
      patients (ie, 61 inpatients and 87 outpatients) with isolated, surgically treated
      ankle fractures were included. After controlling for confounding variables,
      outpatient care was associated with 31.6% lower costs compared with inpatient
      care. Obese patients had 21.6% higher costs compared with patients who were not
      obese. No difference was noted in revision surgery, readmission, or return visits
      to the emergency department for patients treated on an inpatient or outpatient
      basis. CONCLUSION: Where medically/socially appropriate, this analysis suggests
      that ankle fracture surgery should be provided in an outpatient surgical facility
      to provide the greatest value to the patient and society. LEVEL OF EVIDENCE:
      Level III.

PMID- 30192249
TI  - Lipomatous Soft-tissue Tumors.
AB  - Lipomatous soft-tissue tumors are the most common neoplasms encountered by
      physicians. They range from benign lipomas to high-grade liposarcomas. Unplanned
      excisions of sarcomas are commonly due to the presumptive diagnosis of lipoma and
      can be avoided by understanding their diagnostic magnetic resonance imaging
      appearance. Magnetic resonance images should be obtained for all soft-tissue
      masses that are deep to fascia or those >5 cm in subcutaneous tissue. Atypical
      lipomatous tumors present as large deep fatty masses and have a propensity for
      local recurrence and a small risk of malignant transformation. Well
      differentiated liposarcomas are histologically identical to atypical lipomatous
      tumors but have a markedly worse prognosis secondary to their anatomic location.
      Masses that lack isointense signal to subcutaneous fat on MRI may represent a
      sarcoma and require a biopsy before definitive treatment. Large deep lipomatous
      masses and liposarcomas should be sent to a sarcoma referral center for
      definitive treatment.

PMID- 30192250
TI  - Outcomes of Arthroscopic Posterior Medial Meniscus Root Repair: Association With
      Body Mass Index.
AB  - INTRODUCTION: The purpose of this study was to assess the association of outcomes
      from posterior medial meniscus root repairs with patient age, sex, and body mass
      index (BMI). METHODS: Patients who underwent arthroscopic posterior medial
      meniscus root repair completed the Knee Injury and Osteoarthritis Outcome Score
      (KOOS) and reported subsequent surgeries. The association of patient factors with
      subsequent surgery and clinical osteoarthritis (OA) based on the KOOS score was
      evaluated. RESULTS: Minimum 2-year follow-up was available on 22/25 patients
      (88%). Two patients (9.1%) had subsequent surgeries, and 10 (45.5%) met the KOOS
      criteria for OA. A BMI over 35 kg/m was associated with repeat surgery (25%
      versus 0%; P = 0.049) and clinical OA (75% versus 28.6%; P = 0.035). CONCLUSION:
      Although arthroscopic repair of posterior medial root tears has good clinical
      outcomes and a low rate of subsequent surgery, an elevated BMI level is
      associated with worse clinical outcomes and a higher rate of subsequent surgery.

PMID- 30192251
TI  - Perioperative Protocol for Elective Spine Surgery Is Associated With Reduced
      Length of Stay and Complications.
AB  - INTRODUCTION: Healthcare reform places emphasis on maximizing the value of care.
      METHODS: A prospective registry was used to analyze outcomes before (1,596
      patients) and after (151 patients) implementation of standardized, evidence-based
      order sets for six high-impact dimensions of perioperative care for all patients
      who underwent elective surgery for degenerative spine disease after July 1, 2015.
      RESULTS: Apart from symptom duration, chronic obstructive pulmonary disease
      prevalence, estimated blood loss, and baseline Oswestry Disability Index, no
      significant differences existed between pre- and post-protocol cohorts. No
      differences in readmissions, discharge status, or 3-month patient-reported
      outcomes were seen. Multivariate regression analyses demonstrated reduced length
      of stay (P = 0.013) and odds of 90-day complications (P = 0.009) for postprotocol
      patients. CONCLUSION: Length of stay and 90-day complications for elective spine
      surgery improved after implementation of an evidence-based perioperative
      protocol. Standardization efforts can improve quality and reduce costs, thereby
      improving the value of spine care. LEVEL OF EVIDENCE: Level III (retrospective
      review of prospectively collected data).

PMID- 30192252
TI  - Reporting the Influence of Sex in Research: Trends at AAOS Annual Meetings.
AB  - BACKGROUND: Several initiatives have urged the inclusion of sex in data analysis,
      but few studies have examined the prevalence of sex-specific reporting in
      musculoskeletal research. This study aims at determining the presence of sex
      specific analyses reported in research at American Academy of Orthopaedic
      Surgeons Annual Meetings. METHODS: Abstracts listed in the American Academy of
      Orthopaedic Surgeons Annual Meeting programs from 2006 to 2013 were
      retrospectively reviewed for the presence of research reporting the results of a
      sex-specific analysis. RESULTS: The number of abstracts reporting a sex-specific
      analysis increased from 48 (2006) to 117 (2013) but accounts for 5.4% of research
      presented from 2006 to 2013. Hip and knee arthroplasty literature accounted for
      37% of included abstracts. CONCLUSIONS: The reporting of sex-specific analyses
      has improved over time but accounts for 5.4% of research presented at annual
      meetings from 2006 to 2013. The inclusion of sex-specific analyses should be
      required for future research publications to better understand the influence of
      sex in musculoskeletal medicine.

PMID- 30192253
TI  - Disparities in Total Hip Arthroplasty Outcomes: Census Tract Data Show
      Interactions Between Race and Community Deprivation.
AB  - INTRODUCTION: Socioeconomic factors such as poverty may mediate racial
      disparities in health outcomes after total hip arthroplasty (THA) and confound
      analyses of differences between blacks and whites. METHODS: Using a large
      institutional THA registry, we built models incorporating individual and census
      tract data and analyzed interactions between race and percent of population with
      Medicaid coverage and its association with 2-year patient-reported outcomes.
      RESULTS: Black patients undergoing THA had worse baseline and 2-year pain and
      function scores compared with whites. We observed strong positive correlations
      between census tract Medicaid coverage and percent living below poverty (rho =
      0.69; P < 0.001). Disparities in 2-year Western Ontario and McMaster Universities
      Osteoarthritis Index (WOMAC) pain and function were magnified in communities with
      high census tract Medicaid coverage. For blacks in these communities, 2-year
      WOMAC function scores were predicted to be -5.54 points lower (80.42 versus
      85.96) compared with blacks in less deprived communities, a difference not
      observed among whites. CONCLUSION: WOMAC pain and function 2 years after THA are
      similar among blacks and whites in communities with little deprivation (low
      percent census tract Medicaid coverage). WOMAC function at 2 years is worse among
      blacks in areas of higher deprivation but is not seen among whites. LEVEL OF
      EVIDENCE: Level II - Cohort Study.

PMID- 30192254
TI  - Novel Surgical Approach to Segmental Bone Transport Using a Magnetic
      Intramedullary Limb Lengthening System.
AB  - Posttraumatic bone defects (BDs) remain a difficult complication for orthopaedic
      surgeons. Surgical goals in these reconstructive cases are to create stable limb
      fixation, maintain limb length, and provide adequate soft-tissue coverage.
      Historically, surgical approaches in these cases have required the use of an
      external fixator, which is associated with several postoperative complications. A
      plate-assisted bone segment transport (PABST) technique using a magnetic limb
      lengthening system eliminates the need for an external fixator and is effective
      for these reconstructive cases. A 51-year-old male patient presented as a
      category I trauma after a motorcycle collision. Osseous injury was defined as
      Gustilo-Anderson type IIIB distal tibia and fibula fracture (AO 42-C2). After
      fixation failure, the PABST technique was performed using a magnetic
      intramedullary limb lengthening system. Radiographic union was achieved 18 months
      postoperatively. This innovative surgical technique is effective in treating
      posttraumatic BDs without the need for limb shortening or the use of an external
      fixator. PABST has the potential to decrease postoperative complications in BD
      reconstructive cases using all-internal technology designed for limb lengthening.
      PABST, in this instance, uses a magnetic intramedullary nail that is controlled
      with a hand-held external remote to allow for precise, adjustable, and
      bidirectional bone segment transport.

PMID- 30192255
TI  - Acetazolamide for Antipsychotic-Associated Weight Gain in Schizophrenia.

PMID- 30192256
TI  - Female Urology and Urogynecology: The Outcome of Patients Participating in Live
      Surgical Broadcasts.
AB  - INTRODUCTION: The aims of this study were to assess the complications and short-
      and long-term outcomes of patients involved in live surgical broadcasts (LSBs) of
      female urology and urogynecological surgery and compare the surgical success with
      operations performed outside this setting by the same surgeons. METHODS: We
      reviewed our prospectively collected database of all patients who had taken part
      in LSBs between 2008 and 2015 for the annual female urology and urogynecology
      course. Data on intraoperative and 30- and 90-day complications and primary
      outcomes from surgery were collected. Procedure-specific success rates were
      determined and compared with the center's previously published success rate for
      these procedures. RESULTS: Overall, 53 females with a median age of 50 years
      (range, 23-77 years) underwent 62 procedures during these LSBs. There were no
      intraoperative complications. There was 1 Clavien-Dindo grade II complication
      within 30 days of surgery. Within 90 days of surgery, there was 1 Clavien-Dindo
      grade III complication, which occurred in a patient having removal of anterior
      pelvic organ prolapse mesh for urethral erosion and simultaneous colposuspension.
      The majority of operations, 57 (92%) of 62, achieved their intended primary
      outcome. CONCLUSIONS: With careful planning, LSB can offer a safe way of sharing
      current operative techniques and decision making with similar 30- and 90-day
      complication rates to standard practices and comparable functional outcomes to
      standard practice.

PMID- 30192257
TI  - Does gestational age affect ultrasonographic findings of the hip in preterm
      newborns? a sonographic study of the early neonatal period.
AB  - There are only a few studies in the literature investigating the effects of
      gestational age on developmental dysplasia of the hip. The aim of this study was
      to investigate the effects of gestational age on hip ultrasound findings in the
      early neonatal period in preterm newborns born between 30th and 36th weeks of
      gestational age. Between January 2008 and December 2013, a total of 788 hips of
      394 premature newborns with a gestational age of up to 36th weeks who underwent
      hip ultrasonography in the first week of their life were retrospectively
      examined. The distribution of roof angles and hip types in terms of sexes was
      compared between groups. Birth weight, birth height, alpha, and beta angles were
      analyzed in terms of the gestational age. The mean gestational age was 33.07
      weeks (SD 2.09; between 30th and 36th). Six hundred and seven hips were
      classified as type I, 154 as type IIa, 21 as type IIc, and 6 as type III. In the
      30th week, type IIc hips in females and type III hips in males were statistically
      significantly higher (P=0.001). In the 34th week, type IIc hips in males were
      statistically significantly higher than the females (P=0.013). In the 35th week,
      type IIa hips in females hips were statistically significantly higher than the
      males (P=0.008). Among all preterm infants, type IIc hips were more common in the
      30th, 31st, 32nd, and 34th weeks, whereas type III hips were statistically
      significantly more common in the 30th week (P=0.0001). The 30th, 31st, 32nd, and
      34th weeks of age are gestational ages that should be considered in terms of
      dysplastic and subluxed hips in premature newborns.

PMID- 30192258
TI  - Hearing and Auditory Processing Abilities in Primary School Children with
      Learning Difficulties.
AB  - OBJECTIVES: This study aimed to investigate hearing and auditory processing
      ability in primary school children with learning difficulties (LD). DESIGN: A
      nonrandomized, cross-sectional single measure research design was used. A total
      of 486 children, aged 7.7 to 10.8 years and attending years 3 and 4 in six
      primary schools, were classified as having an LD (n = 67) or being typically
      developing (TD, n = 419). This classification was based on a Learning Score
      generated from their school report results and National Assessment Program -
      Literacy and Numeracy scores. All children attempted a conventional hearing
      assessment (CHA) involving pure-tone audiometry, tympanometry, acoustic reflexes
      (AR), and otoacoustic emissions (OAEs). Children returning pure-tone audiometry
      results within normal limits also attempted an auditory processing assessment
      (APA) including dichotic digits (DD) and low-pass filtered speech (LPFS) tests.
      RESULTS: In children with LD, 21/67 (31.4%) failed the CHA, 20/58 (34.5%) failed
      the APA, and 32/58 (55.2%) failed the overall hearing assessment (OHA) if they
      failed either or both CHA and APA. In comparison, in TD children, 55/413 (13.3%)
      failed the CHA, 52/314 (16.6%) failed the APA, and 86/313 (27.5%) failed the OHA.
      Proportionally, children with LD were 2.4 times more likely than TD children to
      fail the CHA, 2.1 times more likely to fail the APA, and 2.0 times more likely to
      fail the OHA. In children who had completed the OHA, multiple linear regressions
      showed average AR thresholds, DD scores, and LPFS scores explained 13 to 18% of
      the variance in the Learning Score. CONCLUSION: The potential for hearing
      impairment should be investigated in children with LD. These investigations
      should begin with CHA, and for children returning normal-hearing thresholds,
      should continue with measures of AR, DD, and LPFS, to ensure these children
      receive the appropriate auditory support needed to enhance their learning.

PMID- 30192259
TI  - Neurohumoral and ambulatory haemodynamic adaptations following isometric exercise
      training in unmedicated hypertensive patients.
AB  - OBJECTIVE: Hypertension remains the leading modifiable risk factor for
      cardiovascular disease. Isometric exercise training (IET) has been shown to be a
      useful nonpharmacological intervention for reducing resting blood pressure (BP).
      This study aimed to measure alterations in office BP, ambulatory BP, cardiac
      autonomic modulation and inflammatory and vascular biomarkers following a
      programme of IET in unmedicated hypertensive patients. METHODS: Twenty-four
      unmedicated stage 1 hypertensive patients (age 43.8 +/- 7.3 years; height, 178.1
      +/- 7 cm; weight 89.7 +/- 12.8 kg) were randomly assigned in a cross-over study
      design, to 4-weeks of home-based IET and control period, separated by a 3-week
      washout period. Office and ambulatory BP, cardiac autonomic modulation, and
      inflammatory and vascular biomarkers were recorded pre and post-IET and control
      periods. RESULTS: Clinic and 24-h ambulatory BP significantly reduced following
      IET by 12.4/6.2 and 11.8/5.6 mmHg in SBP/DBP, respectively (P < 0.001 for both),
      compared with the control. The BP adaptations were associated with a significant
      (P = 0.018) reduction in the average real variability of 24-h ambulatory BP
      following IET, compared with control. Cardiac autonomic modulation improved by
      11% (P < 0.001), baroreceptor reflex sensitivity improved by 47% (P < 0.001), and
      IL-6 and asymmetric dimethylarginine reduced by 10% (P = 0.022) and 19% (P =
      0.023), respectively, which differed significantly to the control period.
      CONCLUSION: This is the first evidence of durable BP reduction and wider
      cardiovascular disease risk benefits of IET in a relevant patient population. Our
      findings support the role of IET as a safe and viable therapeutic and preventive
      intervention in the treatment of hypertension.

PMID- 30192260
TI  - Does Free-Text Information in Falls Incident Reports Assist to Explain How and
      Why the Falls Occurred in a Hospital Setting?
AB  - OBJECTIVE: The aim of this study was to explore whether information captured in
      falls reports in incident management systems could be used to explain how and why
      the falls occurred, with a view to identifying whether such reports can be a
      source of subsequent learnings that inform practice change. METHODS: An analysis
      of prospectively collected falls incident reports found in the incident
      management systems from eight Western Australian hospitals during a stepped-wedge
      cluster-randomized controlled trial. The falls reported occurred in a cohort of
      older hospital patients (mean age = 82 y) on rehabilitation wards. Data coded
      from free-text comments in the incident reports were analyzed using deductive
      content analysis. RESULTS: In the 493 analyzed falls incident reports,
      qualitative information describing aspects of the fall that clarified the
      patient, staff, and environment-related contributory factors was consistently
      low. Reports infrequently contained information about patients' and staff's call
      bell use behaviors (13%-19% of reports), fidelity of implementation of the care
      plan (8%) or environment-related factors such as bed settings (20%), and presence
      of clutter at the fall location (1%). The patients' account of the fall was
      present in less than 50% of reports, with an absence of concurrent text, which
      explained whether patient cognitive impairment was the reason for not obtaining
      this first-person account of the incident. CONCLUSIONS: Falls reports in hospital
      incident management systems may not capture adequate information to explain how
      and why falls occur. This could limit creation of effective feedback loops to
      drive quality improvement efforts and targeted practice change.

PMID- 30192261
TI  - Lung protection during one-lung ventilation: Another piece in the puzzle.

PMID- 30192262
TI  - Removal of entrapped epidural catheter: role of muscle relaxation.

PMID- 30192263
TI  - An observational study of skill retention and practice adoption after a workshop
      on ultrasound-guided neuraxial anaesthesia.

PMID- 30192264
TI  - Modified half-the-air technique for continuous pressure monitoring during lumbar
      plexus block.

PMID- 30192265
TI  - The feasibility of pressure measurement during an ultrasound-guided thoracic
      paravertebral block.

PMID- 30192266
TI  - A case for civility in publishing.

PMID- 30192267
TI  - Keeping up-to-date with diabetes care and education.
AB  - The American Diabetes Association publishes standards of care that are updated
      annually by a panel of experts in nursing, education, behavior, psychology,
      nutrition, pharmacology, and medicine. This article describes current evidence
      based approaches to care and education for adults and highlights revisions in the
      2018 Standards of Care that are relevant to nurses and patients with type 2
      diabetes.

PMID- 30192269
TI  - Specialty Focus: Trauma Issue.

PMID- 30192268
TI  - New Drugs 2018, part 3.
AB  - This article discusses eight drugs recently approved by the FDA, including their
      indications and contraindications, precautions, dosage, and nursing
      considerations. The article also includes summary charts on 14 recently approved
      antineoplastic drugs and four drugs approved for rare disorders.

PMID- 30192270
TI  - Autumn Reflections.

PMID- 30192272
TI  - Hidden in Plain Sight: A Guide to Human Trafficking for Home Healthcare
      Clinicians.
AB  - Human trafficking is a global problem reaping $150 billion annually, mainly from
      commercial sex or forced labor activities involving adult and child victims.
      Eighty-seven percent of human trafficking victims are known to have been seen by
      a healthcare provider at least once during the time held captive, but due to lack
      of awareness, this opportunity to identify and aid victims is often missed. Home
      healthcare providers have access to homes where human trafficking victims may be
      hidden in plain sight. It is critical that home healthcare providers know the
      signs of human trafficking, how to screen a potential victim, how to report any
      suspicious activities, and ways to remain safe while working in the community. If
      a human trafficking victim or perpetrator is identified or even suspected, home
      healthcare providers should move to a safe location and call the 24/7 National
      Human Trafficking Hotline (1-888-373-7888).

PMID- 30192273
TI  - Lice Update: Management and Treatment in the Home.
AB  - Lice infestation is a common health issue affecting 6 to 12 million school-age
      children in the United States each year, impacting all members of the household.
      The home care nurse can be a valuable resource in the management of lice in the
      home and can assist the family in understanding the various myths and
      misconceptions about lice. This article provides an overview of lice management,
      including identification and treatment of a lice infestation as well as
      recommendations for environmental control strategies in the home. It includes an
      overview of the various over-the-counter and prescription treatment options and
      highlights the social stigma that is often associated with a lice infestation.

PMID- 30192274
TI  - Medication Literacy and Somali Older Adults Receiving Home Care.
AB  - Medication literacy is the ability of individuals to access and understand
      medication information and then use that information to act and take their
      medication in a safe and appropriate way. The purpose of this study was to
      explore medication literacy in a group of Somali older adults and their families
      using qualitative secondary analysis. We conducted an analytic expansion of an
      existing qualitative study that explored the home healthcare perceptions of
      Somali older adults and their families. Qualitative data collected from 14 Somali
      families about home healthcare were reviewed and analyzed for material related to
      medication literacy. Data analysis revealed a number of important findings
      related to medication literacy and resulted in the discovery of four themes:
      Medication literacy is needed among Somali older adults and their families, Using
      home healthcare (HHC) to improve medication literacy, Better communication is
      essential to improving medication literacy, and Medication literacy is an
      intersecting family and social issue. The results of this study indicate that HHC
      has a role to play in improving the health and medication literacy of these
      families. They also highlight the need to further explore what techniques, tools,
      and/or supports HHC professionals need to care for non-English speaking
      populations. Future research needs to address how to meet the needs of diverse
      and vulnerable patients like Somali older adults, and how best to prepare HHC
      providers to do this.

PMID- 30192275
TI  - Physical Therapy Self-Management Strategies for a Patient With a Total Hip
      Replacement and Heart Failure: A Case Report.
AB  - : Heart failure (HF) is the most common reason for admission to the hospital in
      people over the age of 65 and has been found to be a possible complication
      following a joint replacement. Self-management education has been shown to reduce
      hospital readmissions rates among patients with HF and to cause significant
      improvements. The purpose of this case report was to describe physical therapy
      (PT) self-management education in the care of a patient with both a recent hip
      replacement (THR) surgery and HF. CASE DESCRIPTION: 85-year-old female with a THR
      and HF. Objective measurements included Timed Up and Go Test (TUG); 10-meter walk
      test (10MWT) and the 6-minute walk test (6MWT). Standard PT care for THR and self
      management education strategies was provided. The patient was seen two times per
      week for nine weeks. Improvements were noted in all outcome measures: (TUG,
      10MWT, 6MWT). The patient was able to meet all ambulation goals and become
      independent in transfers. In this case, self-management education was shown to
      provide positive benefits by increasing functional mobility and helping prevent
      further complications from HF. Self- management education in the home health
      setting is important for older adult patients who had a THR.

PMID- 30192276
TI  - Older Adults With Unintended Weight Loss: The Role of Appetite Stimulants.
AB  - The increasing older adult population guarantees that healthcare providers are
      more likely to encounter patients requiring treatment for unintended weight loss.
      Due to physiologic changes that occur in the older adult, it is important to know
      how to assess for, and diagnose unintended weight loss, as well as understand the
      treatment options. In addition to the use of enteral and parenteral nutrition,
      appetite stimulants have been used in older adults. Understanding the dosage,
      side effects, and proper usage of appetite stimulants, such megestrol acetate,
      mirtazapine, and dronabinol, is crucial in order to provide safe and effective
      patient care.

PMID- 30192277
TI  - Red Flags and Off Ramps: Providing Community Education About Driving and
      Dementia.
AB  - Driving safety for older adults with dementia presents a continuing complex
      challenge in the community. More than 5 million people in the United States
      suffer from dementia, and their numbers are expected to grow. Evidence-based
      resources to identify and manage driving risks in older adults with dementia do
      exist, but the challenges of limited time in primary care and outpatient settings
      can make application difficult. This innovative project, funded by a Hartford
      Foundation Change Agents Action grant award, focused on interprofessional work to
      address the educational need for primary care professionals and family caregivers
      to manage driving safety for their loved ones with dementia. An interactive
      theater performance with development of an educational DVD was tested in a sample
      of professional and family caregivers. This project also forged new sustainable
      interprofessional community partnerships among educators/researchers and
      healthcare providers caring for this vulnerable community population.

PMID- 30192278
TI  - African American Spirituality and Diabetes Self-Care.

PMID- 30192280
TI  - Function at the Heart of Therapy.

PMID- 30192281
TI  - Possible Reason for Hyperglycemia in Patients Using an Insulin Pen.

PMID- 30192279
TI  - Healthy Aging: How It's Done.

PMID- 30192282
TI  - Trump Labor Department Breathes New Life Into Obama-Era Wage Regulation.

PMID- 30192283
TI  - Evolving Threat of Candida Resistance.

PMID- 30192284
TI  - A Day in the Life of Hunter the Therapy Dog.

PMID- 30192286
TI  - Are You Being Watched?

PMID- 30192285
TI  - Widely Fluctuating International Normalized Ratios (INRs).

PMID- 30192287
TI  - An Encounter That Changed My Perspective on Spiritual Care.

PMID- 30192288
TI  - Hidden in Plain Sight: A Guide to Human Trafficking for Home Healthcare
      Clinicians.

PMID- 30192289
TI  - Intraoral Anastomosis of Deep Circumflex Iliac Artery Perforator Flap for
      Maxillary Reconstruction.
AB  - Maxillary reconstruction is one of the most challenging areas of reconstructive
      surgery. This report describes a case of a 33-year-old male with osteoblastic
      osteosarcoma of the maxillary. The patient received radical resection and
      reconstruction with a deep circumflex iliac artery perforator flap (DCIAPF). The
      flap was harvested with a 4 * 2 cm osseous flap and a 6 * 8 cm skin island
      supplied by terminal perforators from the deep circumflex iliac artery.
      Anastomosis was accomplished on the ipsilateral facial vessels with deep
      circumflex iliac vessels through an intraoral approach. The donor site and the
      flap were observed to have completed primary healing 2 weeks after the surgery.
      The DCIAPF may be a satisfactory single-flap option for maxillary reconstruction
      with less donor-site complications.

PMID- 30192290
TI  - Evaluation the Efficacy of Hilotherm Cooling System in Reducing Postoperative
      Pain and Edema in Maxillofacial Traumatized Patients and Orthognathic Surgeries.
AB  - Surgical treatment in patients with facial bone surgeries governs a meaningful
      extent of tissue trauma prompting prevalent postoperative portents of pain,
      facial swelling, and inconvenience. Beneficial effects of local cold therapy
      following surgery, facial swelling, pain, and inflammation have been discussed.
      The aim of study is to evaluate the efficacy of hilotherm cooling system in
      reducing postoperative pain and edema in patients following maxillofacial trauma
      and orthognathic surgeries.A clinical prospective study was done in the
      postoperative period for patients with facial trauma or those subjected to
      orthognathic surgery, 34 patients divided randomly into 2 groups; study group
      treated with the hilotherm cooling system and control group without. Facial
      swelling was quantified by 5 linear distances (A, B, C, D, and E). Pain was
      reported on day 1, 2, and 7 postoperatively. Satisfaction with cooling therapy at
      day 7 following surgery was recorded. The means of swelling variation in study
      group were less than in control group with highly significant difference (P <
      0.01) except in (line D) which is from tragus to the chin most prominent point
      where it was significant. Pain scores in control group were higher than in study
      group with highly significant difference (P < 0.01) except at 7th day which was
      not significant (P > 0.05). All patients in the study group were very satisfied.

PMID- 30192291
TI  - Effect of Septoplasty on Cardiopulmonary Functions in the Patients With Nasal
      Obstruction.
AB  - OBJECTIVE: In this study, the authors aimed to investigate whether septoplasty
      has an effect on cardiopulmonary functions in the patients with nasal
      obstruction. METHODS: A total of 53 patients with nasal obstruction due to septum
      deviation were included in the study. All the patients were performed septoplasty
      operation. Echocardiography and spirometric analysis were performed to assess
      cardiopulmonary functions before and after the operation (6 months
      postoperatively). The same evaluation was done for the degree of nasal
      obstruction by visual analogue scale. The preoperative and postoperative values
      were compared with each other. RESULTS: Of the total 53 patients, 44 were males
      (83%) and 9 were female (17%). The mean age was 31.71 +/- 9.46. The preoperative
      and postoperative mean right ventricular volumes were 2.0736 and 2.0906,
      respectively. The preoperative and postoperative mean left ventricular volumes
      were 4.4264 and 4.3528, respectively. The preoperative and postoperative mean
      cardiac septal thicknesses were 0.9642 and 0.9358, respectively. The mean value
      of preoperative cardiac posterior wall thicknesses was 0.8849, whereas the
      postoperative value was measured as 0.8340. The preoperative and postoperative
      mean pulmonary artery pressures were 27.8302 mmHg and 23.6415, respectively, and
      this was statistically significant (P < 0.001). The preoperative and
      postoperative mean forced vital capacities (FVC) were 4.3221 and 4.5564,
      respectively, and this was statistically significant (P < 0.001). The
      preoperative and postoperative mean 1st second forced expiratory volumes (FEV1)
      were 3.6698 and 3.8085, respectively, and this was statistically significant (P <
      0.001). The mean value of preoperative FEV1/FVC was 84.9811, whereas
      postoperative mean value was measured as 83.8019 and this was statistically
      significant (P < 0.001). CONCLUSION: In this study, the authors observed that
      septoplasty has positive effect on cardiopulmonary functions in the patients with
      nasal obstruction due to nasal septum deviation. The authors also claim that
      septoplasty may be a preventive procedure for future pathologies of
      cardiopulmonary functions.

PMID- 30192293
TI  - Microvascular Replantation of the Avulsed Lip.
AB  - Traumatic facial soft tissue injury often creates both aesthetic and functional
      deficits. In complete lip avulsions, microvascular replantation is a
      reconstructive option that has the potential to fulfill both of these goals.
      However, lip replantations remain rare and there are few reports in the
      literature. The authors aim to present a clinical report of a young male who
      sustained a human bite injury and underwent microvascular replantation of a
      completely avulsed lower lip and to review the literature and management of these
      complex injuries.

PMID- 30192292
TI  - Do Mandibular Third Molars Play a Role in Fractures of the Mandibular Angle and
      Condyle?
AB  - INTRODUCTION: The relationship between impacted mandibular third molars with
      angle and condylar fractures is subject of many publications, yet their
      conclusions differ widely, hence the authors wanted to investigate this topic in
      their patients. METHODS: The authors designed a retrospective study including 241
      patients who presented with angle and/or mandibular condyle fractures over a 13
      year period at the authors' institution. The study variable was the
      presence/absence of third molars. The authors used the Pell and Gregory system to
      classify their position, whereas the angulation was classified using Archer
      classification. The outcome variables were the presence of angle and condylar
      fractures. Other study variables included fracture etiology. RESULTS: Assaults
      were the most frequent cause of angle fractures (62.7%), whereas falls were
      mostly responsible for condylar fractures (79.6%). Angle fractures were mostly
      isolated (66.3%), whereas condylar fractures were mostly associated with other
      fractures (62.6%). The majority of the angle fractures occurred in patients with
      third molars (63.6%), on the contrary the majority of the condylar fractures
      occurred in patients without mandibular third molars (78.3%). Angle fractures
      were mostly associated with fully erupted or superficially impacted third molars
      (90,9%). Finally in the presence of mesioangulated third molars, condylar
      fractures did not happen in 83.8% of patients. CONCLUSIONS: According to the
      authors' findings, fully erupted or superficially impacted mandibular third
      molars are a risk factor for angle fractures but at the same time a protective
      factor for the condyle. On the contrary, the absence of mandibular third molars
      "strengthens" the angle and represents a risk factor for condylar fractures.

PMID- 30192294
TI  - Ophthalmic Injuries Related to Maxillofacial Trauma Due to Urban Warfare.
AB  - : : Midfacial trauma commonly causes ocular injuries of varying degrees. Eye
      injuries account for approximately 10% of all battle injuries. Severity of
      injuries may range from a subconjunctival haemorrhage to optic nerve injury and
      globe laceration and rupture. AIM OF STUDY: Is to evaluate the associated
      ophthalmic injuries in maxillofacial trauma due to war and to emphasize the need
      for proper ophthalmic examination to exclude and manage any associated ophthalmic
      injuries. MATERIALS AND METHODS: A total of 66 patients with maxillofacial trauma
      due to war were considered in this study and underwent classification of the
      fractures to know patterns of fractures and to specify the ophthalmic injuries
      which might be associated with each fracture. Referral to ophthalmologist was
      considered to determine the exact nature of ophthalmic injuries. Results by a
      maxillofacial surgeon and ophthalmologist were evaluated. RESULTS: Midfacial
      trauma particularly those associated with zygomatic bone fracture was highly
      significant due to blast and bullets can lead to serious ophthalmic injuries.
      This was related to 57% of ophthalmic injuries. The related ocular injuries which
      were subconjunctival hemorrhage and the rupture or lacerated eye globe found to
      be highly significant war injuries while the preretinal hemorrhage and diplopia
      were significant. CONCLUSION: A thorough proper ophthalmic examination should be
      carried out for every patient with these fractures and suspected cases should be
      placed under close observation so that immediate and active treatment can be
      taken if necessary.

PMID- 30192295
TI  - Oculocardiac Reflex as a Late Presentation of Orbital Floor Fracture.
AB  - Delayed repair of orbital trapdoor fractures can jeopardize the viability of
      entrapped contents and prolong recovery. Variation in presentations, both
      clinically and radiographically, complicate prompt diagnosis. The oculocardiac
      reflex may be the only indication of fracture with entrapped orbital contents,
      but, unfortunately, the reflex has variable onset patterns and can mimic common
      diagnoses. Therefore, the authors present the case of a 14-year-old male with a
      right orbital floor fracture, who presented with delayed symptoms secondary to an
      oculocardiac reflex. The vagal sequelae of the reflex, including gastric
      hyperactivity and headache, were experienced approximately 1 week after the
      injury and caused the patient to be misdiagnosed with gastroenteritis and status
      migrainosus, on 2 separate hospital visits. After admission to the hospital due
      to progressive symptoms, a CT scan showed concerns for a subacute orbital blowout
      fracture. The patient underwent orbital floor exploration with findings of
      scarred orbital fat herniating into a healing fracture site. Repositioning of the
      fat into the orbit resulted in immediate resolution of the patient's symptoms.
      Awareness of the presenting characteristics of the oculocardiac reflex can lead
      to prompt diagnosis and maximize clinical outcomes.

PMID- 30192296
TI  - Porous Polyethylene Implant Associated With Delayed Orbital Complications and
      Osteomyelitis After Orbital Reconstruction.
AB  - Orbital implants are commonly used to repair orbital blowout fractures, to
      restore the functional and anatomical structure of the orbit. Porous polyethylene
      implants are a type of alloplastic implant and are widely used for orbital
      reconstruction as micropores facilitate the growth of fibers and blood vessels
      through the material. Rare complications associated with porous polyethylene
      implants used to treat blowout fractures include delayed orbital inflammation and
      osteomyelitis. The authors describe a 68-year-old man who presented with a 5-year
      delayed porous polyethylene implant infection and cicatricial ectropion with
      osteomyelitis after an orbital blowout fracture repair. The patient underwent
      surgery to incision and drainage of orbital abscess with ectropion correction
      surgery. He was treated with intravenous antibiotics for 6 weeks due to
      osteomyelitis and made a good recovery.

PMID- 30192297
TI  - Epineurial Nerve Coaptation: A Biological Nonliving Training Model Using
      Gradually Thawed Cryopreserved Sciatic Nerves.
AB  - The authors present a novel biological nonliving epineurial nerve coaptation
      training model, which allows cost-efficient practicing on organic mammal nerves
      and offers an objective performance control on the basis of successful suturing
      and respecting the 3R model.Anatomic dissection of 40 rat cadavers was performed.
      Four residents without prior microneurosurgical experience were included. Each
      trainee performed 20 epineurial nerve coaptations. The number of successful
      sutures served as qualitative variable and operation time as a quantitative
      variable for efficiency control.The rate for successful sutures was 51.9% in the
      first half of trials and improved to 94.4% in the second half. Whereas, the
      trainees needed a mean time of 34 minutes for the first 10 coaptations, the last
      10 coaptations were performed within 24.5 minutes.The authors' presented model is
      an easily accessible, low-cost microneurosurgical simulation model, allowing a
      realistic and instructive performance of epineurial nerve coaptation. Because
      cadaveric nerves are used, an approval of the local ethics committee is not
      needed. Furthermore, anatomic knowledge about the topography related to the
      harvest of the sciatic nerve of rats is provided in this study.

PMID- 30192298
TI  - The Boomerang Epicanthoplasty: A Technique That Avoids Hooding.
AB  - Redraping is an increasingly common epicanthoplasty method. However, hooding
      usually remains at the medial part of the upper eyelid. The authors innovated a
      modification of redraping epicanthoplasty using excision, resulting in a
      boomerang-shaped defect that does not lead to hooding of the medial upper
      eyelid.Medial line (M-line) was drawn at the most medial point of the palpebral
      fissure. The canthus point (C-point) was marked approximately 1 to 3 mm laterally
      from the M-point, depending on the amount of widening needed. From the C-point,
      upper incision was designed to meet the double eyelid line. A V-shaped lower
      incision was designed 3 to 4 mm below the ciliary margin. A flap was elevated
      about 7 mm superiorly, 10 mm medially, and 5 mm inferiorly. The elevated skin
      flap was redraped and the M'-point, which reflected the M-point on the redraped
      skin, was marked. A curvilinear incision line reflecting previous incision lines
      was drawn. The crescent-shaped excess skin was excised and the medial canthus was
      retracted medially, and then the boomerang-shaped defect was observed. The M
      point and M'-point were coapted with a suture. The dog-ear at the lower side was
      trimmed.The 525 patients were followed up for >=3 months postoperatively. The
      average increase in the palpebral fissure length was 1.2 +/- 0.5 mm. The average
      decrease in the interepicanthal distance was 2.4 +/- 0.9 mm. The average
      satisfaction score was 4.6 +/- 0.6.Boomerang epicanthoplasty can prevent hooding
      on the medial aspect of the upper eyelid. It is easy to design, requires marking
      only 1 point, and is tension-free, thereby reducing scar widening.

PMID- 30192299
TI  - Respiratory Pathway and Swallowing Management in a Patient With Epiglottis Loss
      After Life-Threatening Penetrating Laryngeal Trauma.
AB  - Laryngeal trauma is a rare but potentially life-threatening injury. Damage to
      larynx structures may occur in forms of a simple contusion, fractures of the
      laryngeal cartilage, and may even result in laryngotracheal disjunction depending
      on the ossification level of the larynx and the severity of the trauma. However,
      in almost all cases, damaged laryngeal tissue is also observed in the trauma
      area. Because thyroid cartilage protects the endolaryngeal tissues like a shield
      against trauma. Epiglottis prevents escape of the food to respiratory tract and
      directs food to digestive system. In this article, a case of knife attack
      resulted in deep neck incision with loss of epiglottis in the incision area, the
      surgical operation, and the postoperative recovery period which had a clinical
      significance due to loss of epiglottis were presented. To the best of our
      knowledge, this is the first laryngeal trauma case with loss of epiglottis.

PMID- 30192301
TI  - Optical measurement of neuronal activity in the developing cerebellum of
      zebrafish using voltage-sensitive dye imaging.
AB  - Voltage-sensitive dye (VSD) imaging enables fast, direct, and simultaneous
      detection of membrane potentials from a population of neurons forming neuronal
      circuits. This enables the detection of hyperpolarization together with
      depolarization, whose balance plays a pivotal role in the function of many brain
      regions. Among these is the cerebellum, which contains a significant number of
      inhibitory neurons. However, the mechanism underlying the functional development
      remains unclear. In this study, we used a model system ideal to study
      neurogenesis by applying VSD imaging to the cerebellum of zebrafish larvae to
      analyze the neuronal activity of the developing cerebellum, focusing on both
      excitation and inhibition. We performed in-vivo high-speed imaging of the entire
      cerebellum of the zebrafish, which was stained using Di-4-ANEPPS, a widely used
      VSD. To examine whether neuronal activity in the zebrafish cerebellum could be
      detected by this VSD, we applied electrical stimulation during VSD imaging, which
      showed that depolarization was detected widely in the cerebellum upon
      stimulation. These responses mostly disappeared following treatment with
      tetrodotoxin, indicating that Di-4-ANEPPS enabled optical measurement of neuronal
      activity in the developing cerebellum of zebrafish. Moreover, hyperpolarizing
      signals were also detected upon stimulation, but these were significantly reduced
      by treatment with picrotoxin, a GABAA receptor inhibitor, indicating that these
      responses represent inhibitory signals. This approach will enable a detailed
      analysis of the spatiotemporal dynamics of the excitation and inhibition in the
      cerebellum along its developmental stages, leading to a deeper understanding of
      the functional development of the cerebellum in vertebrates.

PMID- 30192300
TI  - Role of receptor-interacting protein 1/receptor-interacting protein 3 in
      inflammation and necrosis following chronic constriction injury of the sciatic
      nerve.
AB  - Nerve damage often leads to nervous system dysfunction and neuropathic pain. The
      serine-threonine kinases receptor-interacting protein 1 (RIP1) and 3 (RIP3) are
      associated with inflammation and cell necrosis. This study aimed to explore the
      role of RIP1 and RIP3 in sciatic nerve chronic constriction injury (CCI) in mice.
      On a total of thirty mice, sciatic nerve CCI was performed. The paw withdrawal
      threshold was measured using Von Frey filaments. The mRNA expression and protein
      levels of inflammatory factors RIP1 and RIP3 in the dorsal root ganglion (DRG),
      spinal cord (SC) and hippocampus (HIP) were also determined. We found that paw
      withdrawal threshold was significantly reduced from the second day after the
      operation, and the levels of tumour necrosis factor-alpha and interferon-gamma in
      DRG, SC and HIP were significantly increased on the eighth and 14th days in CCI
      mice. Furthermore, the downstream signalling molecules of RIP1 and RIP3, GTPase
      dynamin-related protein-1, NLR family pyrin domain containing-3 (NLRP3) and
      nuclear factor kappaB-p65 were upregulated. Increased protein levels of
      programmed cell death protein 1, which indicate cell death of peripheral and
      central nervous tissue, were induced by CCI of the sciatic nerve. Overall, this
      study showed that RIP1 and RIP3 were highly expressed in DRG, SC and HIP of the
      sciatic nerve in CCI mice and may be involved in chronic neuroinflammation and
      neuronecrosis.

PMID- 30192302
TI  - Melanoma diagnosis: predictive value of macroscopic changes observed by the
      patient.
AB  - About half of the melanomas are detected by patients but the mean thickness of
      such melanomas is higher than when diagnosed by physicians. Symptoms and signs
      described by patients are dynamic changes and pruritus, the appearance of a new
      lesion having been rarely investigated. These observations are documented for
      melanomas but not for benign naevi. To the best of our knowledge, this is the
      first study in which both melanomas and suspected excised naevi were included.
      The main objectives were to (a) analyse the value of the anamnestic predictors
      for melanoma versus non-melanoma and (b) calculate the influence of age on the
      most significant anamnestic predictors. In order to reach these objectives, we
      prospectively collected data on symptoms (pruritus, anxiety) and signs (de novo
      appearance, dynamic changes and bleeding) described by patients undergoing the
      excision of lesions clinically diagnosed as melanocytic and considered as
      suspicious by 46 Belgian dermatologists. Among 1865 lesions, dynamic changes and
      de novo appearance were significant predictors for melanoma versus non-melanoma
      diagnosis in all patients and patients older than 50, respectively. More
      precisely, dynamic changes and de novo appearance occurred to be strong
      predictors for melanoma diagnosis in patients greater than 41.5 and greater than
      44.5 years, respectively. Pruritus was not significant for melanoma diagnosis. As
      a conclusion, when mid-age or older patients observe melanocytic lesions as
      recently changed or newly appeared, such lesions should be considered more
      carefully than when observed by young patients.

PMID- 30192305
TI  - Blood pressure response to bicycle exercise testing in athletes: what is
      'normal'?

PMID- 30192304
TI  - The Impact of Tobacco Cigarette Smoking on Spinal Cord Stimulation Effectiveness
      in Chronic Spine-Related Pain Patients.
AB  - BACKGROUND AND OBJECTIVES: Despite the observation that select nicotine receptor
      agonists have analgesic effects, smokers report higher pain scores and more
      functional impairments than lifelong nonsmokers, attributable to exaggerated
      stress responses, receptor desensitization, and altered pharmacokinetics
      compounded by accelerated structural damage resulting from impaired bone healing,
      osteoporosis, and advancement of disk disease. We hypothesized that smoking
      diminishes the analgesic response to spinal cord stimulation (SCS) in patients
      with chronic spine-related pain conditions. METHODS: A retrospective cohort study
      was performed at Cleveland Clinic by collecting and assessing data of 213
      patients who had been implanted with SCS for spine-pain indications. History of
      tobacco smoking was subcategorized into 3 categories: past (former smoker),
      present (current smoker), or those who had never previously smoked (lifelong
      nonsmokers), and a multivariable linear regression was run to measure the
      correlation, if any, between smoking status and numerical rating scale pain
      score. In addition, opioid consumption at baseline and 12-month follow-up,
      expressed in milligram oral morphine equivalents, was collected and compared.
      RESULTS: Adjusted for differences, at 1-year follow-up, current smokers (n = 62)
      reported numerical rating scale pain score of 7.0, which is 1.93 (P < 0.001) and
      1.32 (P = 0.001) points higher than those of lifelong nonsmokers (n = 77) and
      former smokers (n = 74), respectively. Opioid intake was 2.4 times higher (P =
      0.004) in smokers than in lifelong nonsmokers. CONCLUSIONS: Among our SCS
      implanted sample, a positive correlation was observed between tobacco use and
      degree of pain reduction as early as 12 months postimplant; this was evident by
      the reported higher pain scores and opioid use in current smokers in comparison
      with former smokers and lifelong nonsmokers.

PMID- 30192303
TI  - The BET-bromodomain inhibitor JQ1 mitigates vemurafenib drug resistance in
      melanoma.
AB  - Inhibition of BRAF improves therapeutic efficacy of BRAF-mutant melanoma.
      However, drug resistance to BRAF inhibitor is inevitable, and the drug resistance
      mechanisms still remain to be elucidated. Here, BRAF mutant cells A375 and SK-MEL
      28 were chosen and treated with BRAF inhibitor vemurafenib, and the results
      showed that the ERK signaling pathway was blocked in these cells. Then,
      vemurafenib-resistant cells were constructed, and we found that drug resistance
      related gene P-gp was overexpressed in the two cell lines. In addition, the
      histone acetylation was significantly increased on the P-gp promoter region,
      which suggested that the epigenetic modification participated in the P-gp
      overexpression. Furthermore, JQ1, a bromodomain inhibitor, was added to the
      vemurafenib-resistant cells and sensitizes the vemurafenib-induced melanoma cell
      apoptosis. In C57BL/6 mice intravenously injected with vemurafenib-resistant
      melanoma cells, cotreatment of vemurafenib and JQ1 also severely suppressed
      melanoma lung metastasis. Taken together, our findings may have important
      implications for the combined use of vemurafenib and JQ1 in the therapy for
      melanoma treatment.

PMID- 30192306
TI  - Isolated systolic hypertension in young adults: a heterogeneous finding.

PMID- 30192308
TI  - Short-term blood pressure variability: does its prognostic value increase with
      ageing?

PMID- 30192307
TI  - Does ECG have additive benefit for predicting atrial fibrillation in patients
      with or without hypertension?

PMID- 30192310
TI  - Evaluation of the impact of aortic root dimension on arterial stiffness in the
      general population: insights from a large Asian population.

PMID- 30192309
TI  - Adrenal venous sampling in dye-allergic primary aldosteronism patients:
      prevalence, pitfalls and a possible solution.

PMID- 30192311
TI  - Reply.

PMID- 30192312
TI  - A possible role of decreased human serum albumin in the endothelial dysfunction
      caused by albuminuria.

PMID- 30192313
TI  - Reply.

PMID- 30192314
TI  - Individualized Medication of Voriconazole: A Practice Guideline of the Division
      of Therapeutic Drug Monitoring, Chinese Pharmacological Society.
AB  - BACKGROUND: Voriconazole (VRZ) is a second-generation triazole antifungal agent
      with broad-spectrum activity. It is available in both intravenous and oral
      formulations, and is primarily indicated for treating invasive aspergillosis. The
      most commonly used dose for adults is 4 mg/kg or 200 mg twice daily. VRZ presents
      nonlinear pharmacokinetics in adults, whereas drug-drug interactions and
      cytochrome P450 2C19 (CYP2C19) polymorphism are of great concern for VRZ. Because
      the liquid chromatography method has been widely used for measuring VRZ blood
      concentration, and target VRZ blood concentration has been recommended in some
      guidelines regarding efficacy and safety, therapeutic drug monitoring is
      considered as a useful tool for VRZ-individualized medication. Also, the CYP2C19
      genotype test is available for guiding relevant drugs use in some health care
      facilities. Our objective was to develop an evidence-based practice guideline for
      VRZ-individualized medication. METHODS: We followed the latest guideline
      definition from the Institute of Medicine and referred to the World Health
      Organization handbook for guideline development. The guideline was initially
      registered in the International Practice Guidelines Registry Platform (IPGRP
      2015CN001). The guideline is, in principle, targeted at all Chinese health care
      providers. The quality of evidence and strength of the recommendations were
      assessed using the Grading of Recommendations Assessment, Development and
      Evaluation (GRADE) method. RESULTS: Twenty-six recommendations were formulated
      regarding therapeutic drug monitoring, special groups of patients, drug safety,
      off-indication use, and drug-drug interactions. Of them, 12 were strong
      recommendations. Most quality of evidence was low, very low, or expert opinions.
      CONCLUSIONS: We developed an evidence-based practice guideline for VRZ
      individualized medication, which provided comprehensive and practical
      recommendations for health care providers. The development of the guideline
      exposed several research gaps to improve VRZ use.

PMID- 30192316
TI  - Histidine-Rich Glycoprotein Suppresses Hyperinflammatory Responses of Lung in a
      Severe Acute Pancreatitis Mouse Model.
AB  - OBJECTIVES: Severe acute pancreatitis is a highly lethal disease caused by
      systemic inflammatory response syndrome, leading to multiple organ failure. We
      recently showed that histidine-rich glycoprotein (HRG) supplemental therapy
      ameliorated septic acute respiratory distress syndrome due to unnecessary
      neutrophil activation and immunothrombosis formation. Here, we evaluated the
      effect of HRG on lung inflammation followed by pancreatitis in a severe acute
      pancreatitis mouse model. METHODS: Mice received intraperitoneal injections of
      cerulein 7 times (100 MUg/kg each) at 1-hour intervals to induce acute
      pancreatitis. Immediately after the first cerulein injection, phosphate-buffered
      saline, human serum albumin (20 mg/kg), or HRG (20 mg/kg) was intravenously
      injected. One hour after the last cerulein injection, phosphate-buffered saline
      or lipopolysaccharide (5 mg/kg) was intravenously injected into the tail vein. We
      evaluated lung inflammatory level after pancreatitis. RESULTS: We observed
      significantly decreased plasma HRG levels in an acute pancreatitis mouse model.
      Histidine-rich glycoprotein treatment inhibited lung edema and the accumulation
      of neutrophil in severe acute pancreatitis, but HRG did not directly affect
      pancreatitis. Moreover, HRG suppressed tumor necrosis factor alpha, inducible
      nitric oxide synthase, interleukin 6, and neutrophil elastase mRNA expression and
      myeloperoxidase activity in the lung. CONCLUSIONS: These data suggested that HRG
      ameliorated lung inflammation secondary to pancreatitis.

PMID- 30192315
TI  - Distinct Inflammatory Changes of the Pancreas of Slowly Progressive Insulin
      dependent (Type 1) Diabetes.
AB  - OBJECTIVE: The aim of this study was to identify the distinct pathological
      changes on the endocrine and exocrine pancreas of slowly progressive insulin
      dependent diabetes mellitus (SPIDDM) or latent autoimmune diabetes in adults.
      METHODS: The pancreases from 12 islet autoantibody-positive SPIDDM patients and
      19 age-matched subjects with no diabetes were examined histologically for islet
      inflammation/insulitis, expressions of cytokines, and enterovirus VP1 protein,
      exocrine pancreatic inflammation, pancreatic ductal changes, major
      histocompatibility complex class I hyperexpression, and amylin-positive amyloid
      in the islets. RESULTS: Insulitis dominant for CD8 T-cells and CD68 macrophages
      was observed in all SPIDDM cases irrespective of duration of diabetes and weight
      of residual beta cells. Major histocompatibility complex class I hyperexpression
      on residual beta cells was observed in SPIDDM. All SPIDDM exocrine pancreases
      showed extensive inflammation, dilated pancreatic ducts, and periductal fibrosis.
      As many as 75% (9/12) of pancreases had pancreatic intraepithelial neoplasia,
      which is assumed to be associated with ductal obstruction/narrowing and exocrine
      pancreatic inflammation, in SPIDDM. Amylin-positive amyloid deposition was not
      detected in SPIDDM. CONCLUSIONS: Persistent insulitis with preserved beta cells
      and major histocompatibility complex class I hyperexpression and exocrine
      pancreatic inflammation with pancreatic intraepithelial neoplasia are distinct
      histological features of SPIDDM pancreas.

PMID- 30192317
TI  - A Meta-Analytic and Scoping Study on Strength Training in People with Multiple
      Sclerosis.
AB  - Aim of the study was to determine a pooled estimate of effect on muscle strength
      and functional capacity induced by strength training in people with multiple
      sclerosis (PwMS).Five databases and 2 public registries were searched from
      inception to May 2017. Indexing terms employed were: "multiple sclerosis",
      "resistance training" and "strength training".Following title/abstract screening,
      two independent reviewers evaluated the studies' eligibility, which were retained
      if PwMS were randomly assigned to strength training or to a no-intervention
      group. Of the 1467 items retrieved, 30 randomized controlled trials (RCTs) formed
      the initial database with 11 trials (426 subjects) entering the final meta
      analysis.The quality of the included studies was assessed by the PEDro scale and
      the risk of bias using the Cochrane Risk-of-Bias tool. All meta-analyses were
      conducted using a random-effects model.Following interventions PwMS increased
      strength by 23.1% (CI 11.8-34.4; +12.1 N; CI 4.5-19.8; p=0.002; n= 366 subjects)
      at a small to moderate effect size (0.37; CI 0.2-0.6). Walking speed increased by
      16.3+/-10.7% (p=0.0002; effect size 0.54; n=275 subjects), distance covered in
      the 2-Minute Walking Test by 6.7+/-6.4% (p=0.04; effect size 0.50; n=111
      subjects.PwMS respond to resistance training with consistent strength gains.
      Methodological inconsistencies among studies and inadequate reporting of the
      findings limited a comprehensive determination of the impact of strength
      improvements on patient functioning, except for walking performance which
      appeared significantly improved. Methodological steps and scoping lines are
      provided to establish a common platform for future trials.

PMID- 30192318
TI  - Diuretics and the Perioperative Fluid Balance.

PMID- 30192319
TI  - Benefits and Early Outcomes of a New Mock Oral Examination for Colorectal
      Surgery.

PMID- 30192320
TI  - The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines
      for the Treatment of Chronic Radiation Proctitis.

PMID- 30192321
TI  - Uncomplicated Sigmoid Diverticulitis.

PMID- 30192322
TI  - Expert Commentary on Uncomplicated Sigmoid Diverticulitis.

PMID- 30192324
TI  - The ALCCaS Trial: A Randomized Controlled Trial Comparing Quality of Life
      Following Laparoscopic Versus Open Colectomy for Colon Cancer.
AB  - BACKGROUND: This study reports the quality-of-life assessment of the ALCCaS
      trial. The ALCCaS trial compared laparoscopic and open resection for colon
      cancer. It reported equivalence of survival at 5 years. Quality of life was
      measured as a secondary outcome. OBJECTIVE: This study aimed to report on the
      quality of life data of the ALCCaS Trial. DESIGN: This study reports a randomized
      controlled trial comparing laparoscopic with open colonic resection. SETTINGS:
      The study was conducted in Australasia. PATIENTS: Patients with a single
      adenocarcinoma of the right, left, or sigmoid colon, presenting for elective
      treatment, were eligible for randomization. INTERVENTIONS: Open and laparoscopic
      colonic resections were performed. MAIN OUTCOME MEASURES: Patient symptoms and
      quality of life were measured using the Symptoms Distress Scale, the Quality of
      Life Index, and the Global Quality of Life Score preoperatively, and at 2 days, 2
      weeks, and 2 months postoperatively. RESULTS: Of the 592 patients enrolled in
      ALCCaS, 425 completed at least 1 quality-of-life measure at 4 time points (71.8%
      of cohort). Those who received the laparoscopic intervention had better quality
      of life postoperatively in terms of the Symptoms Distress Scale (p < 0.01),
      Quality of Life Index (p < 0.01), and Global Quality of Life (p < 0.01). In
      intention-to-treat analyses, those assigned to laparoscopic surgery had a better
      quality of life postoperatively in terms of the Symptoms Distress Scale (p <
      0.01) and Quality of Life Index (p < 0.01), whereas Global Quality of Life was
      not significant (p = 0.056). The subscales better for laparoscopic resection at
      all 3 postoperative time points were appetite, insomnia, pain, fatigue, bowel,
      daily living, and health (p < 0.05). LIMITATIONS: The primary limitation was the
      different response rates for the 3 quality-of-life measures. CONCLUSIONS: There
      was a short-term gain in quality of life maintained at 2 months postsurgery for
      those who received laparoscopic relative to open colonic resection. See Video
      Abstract at http://links.lww.com/DCR/A691.

PMID- 30192323
TI  - Consolidation mFOLFOX6 Chemotherapy After Chemoradiotherapy Improves Survival in
      Patients With Locally Advanced Rectal Cancer: Final Results of a Multicenter
      Phase II Trial.
AB  - BACKGROUND: Adding modified FOLFOX6 (folinic acid, fluorouracil, and oxaliplatin)
      after chemoradiotherapy and lengthening the chemoradiotherapy-to-surgery interval
      is associated with an increase in the proportion of rectal cancer patients with a
      pathological complete response. OBJECTIVE: The purpose of this study was to
      analyze disease-free and overall survival. DESIGN: This was a nonrandomized phase
      II trial. SETTINGS: The study was conducted at multiple institutions. PATIENTS:
      Four sequential study groups with stage II or III rectal cancer were included.
      INTERVENTION: All of the patients received 50 Gy of radiation with concurrent
      continuous infusion of fluorouracil for 5 weeks. Patients in each group received
      0, 2, 4, or 6 cycles of modified FOLFOX6 after chemoradiation and before total
      mesorectal excision. Patients were recommended to receive adjuvant chemotherapy
      after surgery to complete a total of 8 cycles of modified FOLFOX6. MAIN OUTCOME
      MEASURES: The trial was powered to detect differences in pathological complete
      response, which was reported previously. Disease-free and overall survival are
      the main outcomes for the current study. RESULTS: Of 259 patients, 211 had a
      complete follow-up. Median follow-up was 59 months (range, 9-125 mo). The mean
      number of total chemotherapy cycles differed among the 4 groups (p = 0.002),
      because one third of patients in the group assigned to no preoperative FOLFOX did
      not receive any adjuvant chemotherapy. Disease-free survival was significantly
      associated with study group, ypTNM stage, and pathological complete response (p =
      0.004, <0.001, and 0.001). A secondary analysis including only patients who
      received >=1 cycle of FOLFOX still showed differences in survival between study
      groups (p = 0.03). LIMITATIONS: The trial was not randomized and was not powered
      to show differences in survival. Survival data were not available for 19% of the
      patients. CONCLUSIONS: Adding modified FOLFOX6 after chemoradiotherapy and before
      total mesorectal excision increases compliance with systemic chemotherapy and
      disease-free survival in patients with locally advanced rectal cancer.
      Neoadjuvant consolidation chemotherapy may have benefits beyond increasing
      pathological complete response rates. See Video Abstract at
      http://links.lww.com/DCR/A739.

PMID- 30192325
TI  - Extended Venous Thromboembolism Prophylaxis After Elective Surgery for IBD
      Patients: Nomogram-Based Risk Assessment and Prediction from Nationwide Cohort.
AB  - BACKGROUND: Identification of risk factors for postoperative venous
      thromboembolism is an important step to reduce the morbidity associated with this
      potentially preventable complication after elective surgery for patients with
      IBD. OBJECTIVE: This study aimed to determine the risk factors for 30-day venous
      thromboembolism after abdominal surgery for patients with venous thromboembolism,
      identify potential indications for extended thromboprophylaxis, and develop a
      nomogram for prediction of risk. DESIGN: This is a retrospective cohort study
      from a prospectively collected database. SETTING: The American College of
      Surgeons National Surgical Quality Improvement Program Participant User File from
      2005 to 2016 was used for data analysis. PATIENTS: All patients with IBD
      undergoing elective abdominopelvic bowel surgery were included. MAIN OUTCOME
      MEASURES: The primary outcomes were the incidence of in-hospital and
      postdischarge venous thromboembolism within 30 days of the index abdominopelvic
      surgery. RESULTS: A total of 24,182 patients met the inclusion criteria. Thirty
      day total and postdischarge rates of venous thromboembolism were 2.5% (n = 614)
      and 1% (n =252). Forty-one percent (252/614) of venous thromboembolism events
      occurred after hospital discharge. Univariate analysis assessed 37 variables for
      association with study outcomes. On multivariate logistic regression analysis,
      older age, steroid use, bleeding disorders, open surgery, hypertension, longer
      operative time, and preoperative hospitalization were associated with venous
      thromboembolism before discharge and also postoperative transfusion, steroid use,
      pelvic and enterocutaneous fistula surgery, and longer operative time were
      associated with venous thromboembolism after discharge. A nomogram was
      constructed for each outcome, translating multivariate model parameter estimates
      into a visual scoring system where the estimated probability of venous
      thromboembolism can be calculated. LIMITATIONS: This study was limited by its
      retrospective nature and the limitations inherent to a database. CONCLUSION:
      Given the higher risk of venous thromboembolism in patients with IBD after
      elective abdominopelvic surgery compared with other indications, an accurate
      prediction of venous thromboembolism before and after discharge using the
      proposed nomogram can facilitate decision making for individualized extended
      thromboprophylaxis in the preoperative setting as a screening tool. See Video
      Abstract at http://links.lww.com/DCR/A711.

PMID- 30192326
TI  - Early Urinary Catheter Removal Following Pelvic Colorectal Surgery: A
      Prospective, Randomized, Noninferiority Trial.
AB  - BACKGROUND: Because of the potential increased incidence of acute urinary
      retention, optimal timing of urinary catheter removal after major pelvic
      colorectal surgery remains unclear. OBJECTIVE: This study aims to compare the
      incidence of urinary retention following early catheter removal on postoperative
      day 1 vs standard catheter removal on day 3. DESIGN: This is a randomized,
      noninferiority trial. SETTING: This study was conducted at an urban teaching
      hospital. PATIENTS: Patients undergoing colorectal surgery below the peritoneal
      reflection were selected. INTERVENTIONS: A 1:1 randomization to early or standard
      catheter removal was performed. Patients in the early arm were administered an
      alpha-antagonist (prazosin 1 mg oral) 6 hours before catheter removal. MAIN
      OUTCOME MEASURES: The primary outcome measured was the incidence of acute urinary
      retention. RESULTS: One hundred forty-two patients were randomly assigned to
      early (n = 71) or standard (n = 71) catheter removal. Mean age was 44.8 +/- 16.9
      years, and the study cohort included 54% men. The most common operations were
      IPAA (66%) and low anterior resection (18%). The overall rate of retention was
      9.2% (n = 13), with no difference between early (n = 6; 8.5%) or standard (n = 7;
      9.9%) catheter removal (RR, 0.86; 95% CI, 0.30-2.42). The risk difference was 
      1.4% (95% CI, -8.3 to 11.1), confirming noninferiority. The rate of infection was
      significantly lower in early vs standard catheter removal (0% vs 11.3%; p =
      0.01). Length of stay was significantly shorter after early vs standard catheter
      removal (4 days, interquartile range = 3-6 vs 5 days, interquartile range = 4-7;
      p = 0.03). LIMITATIONS: Patients and investigators were not blinded; a
      nonselective oral alpha-antagonist was used. CONCLUSIONS: Following pelvic
      colorectal surgery, early urinary catheter removal, when combined with the
      addition of an oral alpha-antagonist, is noninferior to standard urinary catheter
      removal and carries a lower risk of symptomatic infection and shorter hospital
      stay. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov (NCT01923129).
      See Video Abstract at http://links.lww.com/DCR/A738.

PMID- 30192328
TI  - Liposomal Bupivacaine Transversus Abdominis Plane Block Versus Epidural Analgesia
      in a Colon and Rectal Surgery Enhanced Recovery Pathway: A Randomized Clinical
      Trial.
AB  - BACKGROUND: Multimodal pain management is an integral part of enhanced recovery
      pathways. The most effective pain management strategies have not been determined.
      OBJECTIVE: The purpose of this study was to compare liposomal bupivacaine
      transversus abdominis plane block with epidural analgesia in patients undergoing
      colorectal surgery. DESIGN: This is a single-institution, open-label randomized
      (1:1) trial. SETTING: This study compared liposomal bupivacaine transversus
      abdominis plane block with epidural analgesia in patients undergoing elective
      open and minimally invasive colorectal surgery in an enhanced recovery pathway.
      PATIENTS: Two hundred were enrolled. Following randomization, allocation, and
      follow-up, there were 92 patients with transversus abdominis plane block and 87
      patients with epidural analgesia available for analysis. INTERVENTIONS: The
      interventions comprised liposomal bupivacaine transversus abdominis plane block
      versus epidural analgesia. MAIN OUTCOME MEASURES: The primary outcomes measured
      were numeric pain scores and the overall benefit of analgesia scores. RESULTS:
      There were no significant differences in the Numeric Pain Scale and Overall
      Benefit of Analgesia Score between groups. Time trend analysis revealed that
      patients with transversus abdominis plane block had higher numeric pain scores on
      the day of surgery, but that the relationship was reversed later in the
      postoperative period. Opioid use was significantly less in the transversus
      abdominis plane block group (206.84 mg vs 98.29 mg, p < 0.001). There were no
      significant differences in time to GI recovery, hospital length of stay, and
      postoperative complications. Cost was considerably more for the epidural
      analgesia group. LIMITATIONS: This study was conducted at a single institution.
      CONCLUSIONS: This randomized trial shows that perioperative pain management with
      liposomal bupivacaine transversus abdominis plane block is as effective as
      epidural analgesia and is associated with less opioid use and less cost. These
      data and the more favorable risk profile suggest that liposomal bupivacaine
      transversus abdominis plane block is a viable multimodal perioperative pain
      management option for this patient population in an established enhanced recovery
      pathway. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov
      (NCT02591407). See Video Abstract at http://links.lww.com/DCR/A737.

PMID- 30192327
TI  - Early Diuresis After Colon and Rectal Surgery Does Not Reduce Length of Hospital
      Stay: Results of a Randomized Trial.
AB  - BACKGROUND: Excessive perioperative fluid administration likely increases
      postoperative cardiovascular, infectious, and GI complications. Early
      administration of diuretics after elective surgery facilitates rapid mobilization
      of excess fluid, potentially leading to decreased bowel edema, more rapid return
      of bowel function, and reduced length of hospital stay. OBJECTIVE: This study
      aimed to evaluate the benefit of early diuresis after elective colon and rectal
      surgery in the setting of an enhanced recovery after surgery practice. DESIGN:
      This was a prospective study. SETTINGS: The study was conducted at a quaternary
      referral center. PATIENTS: A randomized, open-label, parallel-group trial was
      conducted in patients undergoing elective colon and rectal surgery at a single
      quaternary referral center. INTERVENTION: The primary intervention was
      administration of intravenous furosemide plus enhanced recovery after surgery on
      postoperative day 1 and 2 versus enhanced recovery after surgery alone. MAIN
      OUTCOME MEASURES: The primary outcome was length of hospital stay. Secondary
      outcomes included 30-day readmission rate, time to stool output during
      hospitalization after surgery, and incidence of various complications within the
      first 48 hours of hospital stay. RESULTS: In total, 123 patients were randomly
      assigned to receive either furosemide plus enhanced recovery after surgery (n =
      62) or enhanced recovery after surgery alone (n = 61). Groups were evenly matched
      at baseline. At interim analysis, length of hospital stay was not superior in the
      intervention group (80.6 vs 99.6 hours, p = 0.564). No significant difference was
      identified in the rates of nasogastric tube replacement (1.6% vs 9.7%, p =
      0.125). Time to return of bowel function was significantly longer in the
      intervention group (45.4 vs 48.8 hours, p = 0.048). The decision was made to end
      the study early because the conditional power of the study favored futility.
      LIMITATIONS: This was a single-center study. CONCLUSIONS: Early administration of
      furosemide does not significantly reduce the length of hospital stay after
      elective colon and rectal surgery in the setting of enhanced recovery after
      surgery practice. See Video Abstract at http://links.lww.com/DCR/A714.

PMID- 30192330
TI  - Life After Surgery: Surgeon Assessments of Quality of Life Among Patients With
      Familial Adenomatous Polyposis.
AB  - BACKGROUND: Without prophylactic surgery, patients with familial adenomatous
      polyposis are at high risk for colorectal cancer development. Various surgical
      options for prophylaxis are available. Patient decision-making for preventative
      treatments is often influenced by the preferences of healthcare providers.
      OBJECTIVE: We determined surgeon preferences for the surgical options available
      to patients with familial adenomatous polyposis. DESIGN: We obtained preference
      estimates for postoperative health states from colorectal surgeons who had
      treated >=10 patients with familial adenomatous polyposis. SETTINGS: Assessments
      were made at an annual meeting of the American Society of Colon and Rectal
      Surgeons. MAIN OUTCOME MEASURES: Utilities were measured through the time trade
      off method. We determined utilities for 3 procedures used for prophylaxis,
      including total proctocolectomy with permanent ileostomy, colectomy with
      ileorectal anastomosis, and total proctocolectomy with IPAA. We also assessed
      utilities for 2 short-term health states: 90 days with a temporary ileostomy and
      2 years with a poorly functioning ileoanal pouch. RESULTS: Twenty-seven surgeons
      who had cared for >1700 patients with familial adenomatous polyposis participated
      in this study. The highest utility scores were provided for colectomy with
      ileorectal anastomosis (0.98). Lower utility scores were provided for total
      proctocolectomy with permanent ileostomy (0.87) and IPAA (0.89). The number of
      patients with familial adenomatous polyposis who were treated by participating
      surgeons did not influence these estimates; however, more-experienced surgeons
      gave lower utility scores for a poorly functioning ileoanal pouch than less
      experienced surgeons (0.15, 0.50, and 0.25 for high-, medium-, and low-volume
      surgeons; p = 0.02). LIMITATIONS: This study was limited by the sample size.
      CONCLUSIONS: For patients with familial adenomatous polyposis and relative rectal
      sparing, surgeon preferences are greatest for colectomy with ileorectal
      anastomosis. Utility estimates provided by this study are important for
      understanding surgical decision-making and suggest a role for ileorectal
      anastomosis in appropriately selected patients. See Video Abstract at
      http://links.lww.com/DCR/A656.

PMID- 30192329
TI  - Intraperitoneal Local Anesthetic Instillation and Postoperative Infusion Improves
      Functional Recovery Following Colectomy: A Randomized Controlled Trial.
AB  - BACKGROUND: Intraperitoneal local anesthetic is an analgesic technique for
      inclusion in the polypharmacy approach to postoperative pain management in
      enhanced recovery after surgery programs. Previously, augmentation of epidural
      analgesia with intraperitoneal local anesthetic was shown to improve functional
      postoperative recovery following colectomy. OBJECTIVE: This study determines
      whether intraperitoneal local anesthetic improves postoperative recovery in
      patients undergoing colectomy, in the absence of epidural analgesia, with
      standardized enhanced recovery after surgery perioperative care. DESIGN: This is
      a multisite, double-blinded, randomized, placebo-controlled trial
      (ClinicalTrials.gov Identifier NCT02449720). SETTINGS: This study was conducted
      at 3 hospital sites in South Australia. PATIENTS: Eighty-six adults undergoing
      colectomy were stratified by approach (35 open; 51 laparoscopic), then randomly
      assigned to intraperitoneal local anesthetic (n = 44) and control (n = 42)
      groups. INTERVENTIONS: Patients in the intraperitoneal local anesthetic group
      received an intraoperative intraperitoneal ropivacaine 100-mg bolus both pre- and
      postdissection and 20 mg/h continuous postoperative infusion for 48 hours.
      Patients in the control group received a normal saline equivalent. MAIN OUTCOME
      MEASURES: Functional postoperative recovery was assessed by using the surgical
      recovery scale for 45 days; postoperative pain was assessed by using a visual
      analog scale; and opioid consumption, use of rescue ketamine, recovery of bowel
      function, time to readiness for discharge, and perioperative complications were
      recorded. RESULTS: The intraperitoneal local anesthetic group reported improved
      surgical recovery scale scores at day 1 and 7, lower pain scores, required less
      rescue ketamine, and passed flatus earlier than the control group (p < 0.05). The
      improvement in surgical recovery scale at day 7 and pain scores remained when
      laparoscopic colectomy was considered separately. Opioid consumption and time to
      readiness for discharge were equivalent. LIMITATIONS: This study was powered to
      detect a difference in surgical recovery scale, but not the other domains of
      recovery, when the intraperitoneal local anesthetic group was compared with
      control. CONCLUSIONS: We conclude that instillation and infusion of
      intraperitoneal ropivacaine for patients undergoing colectomy, including by the
      laparoscopic approach, decreases postoperative pain and improves functional
      postoperative recovery. We recommend routine inclusion of intraperitoneal local
      anesthetic into the multimodal analgesia component of enhanced recovery after
      surgery programs for laparoscopic colectomy. See Video Abstract at
      http://links.lww.com/DCR/A698.

PMID- 30192331
TI  - The Effect of Nonoperative Management of Chronic Anal Fissure and Hemorrhoid
      Disease on Bowel Function Patient-Reported Outcomes.
AB  - BACKGROUND: Nonoperative management has been reported to decrease symptoms from
      common anorectal conditions such as chronic anal fissures and hemorrhoids. The
      effects of these interventions on bowel function are unknown. OBJECTIVE: This
      study aims to perform a prospective evaluation of patient-reported outcomes of
      bowel function on nonoperative management for chronic anal fissures and
      hemorrhoid disease. DESIGN: This is a prospective, observational study. SETTINGS:
      Patient-reported outcome measures were collected from the clinical practice of
      the division of colon and rectal surgery at a tertiary colon and rectal surgery
      referral center. INTERVENTION: All patients received standardized dietary
      counseling including fiber supplementation as well as toileting strategies. Those
      with chronic anal fissures were also prescribed topical calcium channel blockers.
      The Colorectal Functional Outcome questionnaire was administered at baseline and
      at first follow-up visit. MAIN OUTCOME MEASURES: The primary outcomes measured
      were the mean change in patient-reported bowel function scores after nonoperative
      management for each disease and in aggregate. RESULTS: A cohort of 64 patients
      was included, 37 patients (58%) with chronic anal fissure and 27 patients with
      hemorrhoid disease. Incontinence, social impact, stool-related aspects, and the
      global score were observed to have statistically significant improvement in the
      aggregate group. When analyzed by diagnosis, hemorrhoid disease demonstrated a
      statistically significant improvement in incontinence and stool-related aspects,
      whereas chronic anal fissure was associated with a statistically significant
      change in social impact, stool-related aspects, and the global score.
      LIMITATIONS: This study was limited by the small cohort size and unclear patient
      adherence to medical management. CONCLUSIONS: Nonoperative management of chronic
      anal fissures and hemorrhoid disease is associated with significant improvement
      in patient-reported outcome scores in several domains, suggesting that dietary
      counseling and medical therapy should be the first-line outpatient therapy for
      these diseases. See Video Abstract at http://links.lww.com/DCR/A726.

PMID- 30192332
TI  - Indocyanine Green Fluorescence Angiography and the Incidence of Anastomotic Leak
      After Colorectal Resection for Colorectal Cancer: A Meta-analysis.
AB  - BACKGROUND: Anastomotic leak is a life-threatening complication of colorectal
      surgery. Recent studies showed that indocyanine green fluorescence angiography
      might be a method to prevent anastomotic leak. OBJECTIVE: The purpose of this
      study was to investigate whether intraoperative indocyanine green fluorescence
      angiography can reduce the incidence of anastomotic leak. DATA SOURCES: Potential
      relevant studies were identified from the following databases: PubMed, Embase,
      Web of Science, Cochrane Library, and China National Knowledge Infrastructure.
      STUDY SELECTION: This meta-analysis included comparative studies investigating
      the association between indocyanine green fluorescence angiography and
      anastomotic leak in patients undergoing surgery for colorectal cancer where the
      diagnosis of anastomotic leak was confirmed by CT and the outcomes of the
      indocyanine green group were compared with a control group. INTERVENTION:
      Indocyanine green was injected intravenously after the division of the mesentery
      and colon but before anastomosis. MAIN OUTCOME MEASURES: The Newcastle-Ottawa
      Scale was used to assess methodologic quality of the studies. ORs and 95% CIs
      were used to assess the association between indocyanine green and anastomotic
      leak. RESULTS: In 4 studies with a total sample size of 1177, comparing the
      number of anastomotic leaks in the indocyanine green and control groups, the ORs
      were 0.45 (95% CI, 0.18-1.12), 0.30 (95% CI, 0.03-2.98), 0.17 (95% CI, 0.01
      3.69), and 0.12 (95% CI, 0.03-0.52). The combined OR was 0.27 (95% CI, 0.13
      0.53). The difference was statistically significant (p < 0.001), and there was no
      significant heterogeneity (p = 0.48; I = 0). LIMITATIONS: Data could not be
      pooled because of the small number of studies; some differences between studies
      may influence the results. Also, the pooled data were not randomized.
      CONCLUSIONS: The result revealed that indocyanine green was associated with a
      lower anastomotic leakage rate after colorectal resection. However, larger,
      multicentered, high-quality randomized controlled trials are needed to confirm
      the benefit of indocyanine green fluorescence angiography.

PMID- 30192333
TI  - Robotic Complete Mesocolic Excision and Para-Aortic Lymph Node Dissection for
      Cecal Cancer and Paraganglioma.

PMID- 30192334
TI  - Lateral Node Dissection in Rectal Cancer in the Era of Minimally Invasive
      Surgery: A Step-by-Step Description for the Surgeon Unacquainted with This
      Complex Procedure with the Use of the Laparoscopic Approach.
AB  - INTRODUCTION: Lateral node dissection in rectal cancer has been routinely
      performed in Eastern countries. Technical and anatomical challenges and potential
      significant postoperative morbidity associated with the procedure have prevented
      its implementation into clinical practice in Western countries. However, the
      minimally invasive approach may offer the opportunity of performing this complex
      procedure with precise anatomical dissection and minimal intraoperative blood
      loss. In this setting, proper training and standardization of technical steps is
      highly warranted for surgeons not fully acquainted with the procedure. TECHNIQUE:
      Access to the lateral nodes along the obturator and internal iliac vessels is
      described by using specific anatomical landmarks. Opening of the peritoneum along
      the ureter provides access to the region of interest. Dissection of the medial
      limit is performed preserving the neurovascular bundle and ureter. The lateral
      dissection is performed along the external iliac vein to provide access to the
      obturator muscle. Identification of the obturator nerve with blunt dissection of
      the fat is a critical part of the procedure. Once the lymphatic connections
      between the inguinal and iliac nodes are transected, dissection is performed
      along the internal iliac vessels, and branches are separated from the
      lymphadenectomy specimen. RESULTS: Evidence supports that lateral node dissection
      performed for highly selected patients with minimally invasive access leads to
      less intraoperative blood loss and similar oncological outcomes. Technical steps
      illustrated in the present video may aid surgeons in performing this procedure
      with precise anatomical landmarks and minimal risk for intraoperative
      complications. CONCLUSIONS: Lateral node dissection for rectal cancer is a
      procedure that may follow standardized technical steps by using precise
      anatomical landmarks with the use of minimally invasive approach.

PMID- 30192335
TI  - Instead of a Sitz Bath, Use a Detachable Shower Head.

PMID- 30192338
TI  - Aging, Women, Poverty, and Health.

PMID- 30192336
TI  - Sitz Baths, Bath Tubs, and Plastic.

PMID- 30192339
TI  - Letter to the Editor And response Letter to the Editor and Author Response of
      Assessment of a Health Promotion Model on Obese Turkish Children. The Journal of
      Nursing Research, 25(6), 436-446.

PMID- 30192340
TI  - The IL-33-ST2 Pathway Contributes to Ventilator-Induced Lung Injury in Septic
      Mice in a Tidal Volume-Dependent Manner.
AB  - Mechanical ventilation (MV) is frequently employed to manage respiratory failure
      in sepsis patients and is required for the surgical management of intra-abdominal
      sepsis. The impact of MV varies dramatically depending on tidal volume, with even
      moderate tidal volume (MTV) ventilation leading to ventilator-induced lung
      injury, whereas low tidal volume (LTV) ventilation protects against sepsis
      induced ARDS. IL-33 is known to contribute to lung injury in sepsis and its
      release can be induced by mechanical stress. To determine the relationship
      between the IL-33-ST2 pathway and patterns of lung injury associated with MV in
      sepsis, mice were subjected to cecal ligation and puncture (CLP) followed six
      hours later by either MTV (10 ml/kg) or LTV (6 ml/kg) ventilation for four hours.
      MTV and LTV ventilation alone for four hours had no impact on lung injury. MTV
      markedly exacerbated lung injury and inflammation, while LTV significantly
      suppressed these parameters in septic mice. Lung and plasma levels of IL-33 ST2
      were significantly elevated by CLP alone at 10 hours. MTV caused further and
      significant increases in IL-33 and sST2 levels, while LTV significantly
      suppressed levels induced by CLP. Deletion of IL-33 or ST2 prevented the increase
      in lung injury and inflammation induced by MTV in septic mice, while
      administration of recombinant IL-33 in the airway reversed the protection seen
      with LTV. Taken together, these findings implicate the IL-33-ST2 pathway in the
      pro-inflammatory changes induced by the mechanical ventilation that leads to lung
      injury in the setting of intra-abdominal sepsis in a tidal volume-dependent
      manner.

PMID- 30192341
TI  - The Effectiveness of Olive Oil in Controlling Morning Inflammatory Pain of
      Phalanges and Knees Among Women With Rheumatoid Arthritis: A Randomized Clinical
      Trial.
AB  - PURPOSE: This study aimed to determine the effectiveness of olive oil in
      controlling morning inflammatory pain of phalanges and knees among women with
      rheumatoid arthritis. DESIGN: This is a randomized clinical trial, which was done
      in Arak, Iran. METHOD: After selecting 60 women based on a convenience sampling
      method, they were randomly allocated into five groups. A demographic
      questionnaire, the Visual Analogue Scale, and the Disease Activity Score 28 were
      completed. After 12 weeks of interventions, the last two scales were again
      completed. All data were analyzed using t test, Kruskal-Wallis test, and Friedman
      test. RESULTS: The mean age of the women was 40 +/- 10.5 years. The result of the
      Friedman test showed a significant difference (p <= .001) among the total mean of
      groups before and after interventions. The post hoc test (least significant
      difference [LSD]) showed a significant difference (p <= .001) between the mean of
      Disease Activity Score 28 in the group using olive oil for massaging. Results
      also showed that there are significant differences (p <= .001) among the mean of
      Visual Analogue Scale rates, among the mean of the number of painful joints, and
      among the mean of the number of swollen joints after intervention in the five
      groups. CONCLUSION: Applying topical extra virgin olive oil, Piroxicam gel, and
      paraffin oil; dry massaging; and taking routine drugs alone were all effective on
      controlling rheumatic arthritis manifestations, respectively. Therefore, applying
      topical extra virgin olive oil for controlling of inflammatory pain of joints in
      rheumatic arthritis is recommended. CLINICAL RELEVANCE: In comparison with other
      medical ointments for RA, olive oil has lower expenditure and is findable in many
      homes.

PMID- 30192342
TI  - Introduction.

PMID- 30192343
TI  - Current Concepts in Acne Pathogenesis: Pathways to Inflammation.
AB  - Acne is a disease of pilosebaceous inflammation. Pivotal in pathogenesis are the
      roles of hormones (insulin, insulin-like growth factor-1, androgens),
      Propionibacterium acnes, lipogenesis, and a proinflammatory lipid profile. Innate
      immune responses are induced through interaction with toll-like receptors and
      inflammasome activation initially and subsequently through adaptive immune
      activation. These insights into pathogenic inflammatory pathways can translate
      into novel therapeutic approaches for acne. Semin Cutan Med Surg 37(supp3):S60
      S62 (c)2018 published by Frontline Medical Communication.

PMID- 30192344
TI  - Advances in Acne and Rosacea Therapy.
AB  - New topical therapies have demonstrated efficacy in patients with moderate or
      severe acne who might otherwise have required therapy with systemic antibiotics
      or isotretinoin. Increasing knowledge about the pathogenesis of acne has
      facilitated the development of therapies with novel modes of action. New and
      investigational therapies also are available or in development for the treatment
      of both the papulopustular and erythematous manifestations of rosacea. Semin
      Cutan Med Surg 37(supp3):S63-S66 (c) 2018 published by Frontline Medical
      Communications.

PMID- 30192345
TI  - Treating Acne in Adult Women.
AB  - Acne can persist into adulthood or erupt de novo at any point after adolescence.
      Adult acne is more common in women than in men. Considerations for treating acne
      in adult women include childbearing potential, pregnancy, lactation, and
      concomitant skin conditions. Semin Cutan Med Surg 37(supp3):S67-S70 (c) 2018
      published by Frontline Medical Communications.

PMID- 30192346
TI  - Treating Acne in Patients With Skin of Color.
AB  - Patients with skin of color are more likely to develop acne and postinflammatory
      hyperpigmentation (PIH). Many therapies for acne have demonstrated efficacy in
      darker skin types and in the treatment of PIH. Semin Cutan Med Surg 37(supp3):S71
      S73 (c) 2018 published by Frontline Medical Communications.

PMID- 30192347
TI  - Dental Management and Prosthetic Rehabilitation of Patients Suffering from
      Hypohidrotic Ectodermal Dysplasia: A Report of Two Case Histories.
AB  - The prosthetic restoration and dental long-term care of two oligodont male
      cousins suffering from X-linked hypohidrotic ectodermal dysplasia is described in
      two case histories. The first patient was three times supplied with removable
      dentures at an age from 5 to 12 years, and the second patient was restored twice
      by tooth- and implant-supported dentures within an observation period of 10
      years. In both patients, implants were placed in the growing jaw (both arches) in
      order to enhance denture retention by single attachments and/or a palatinal bar.
      In one patient, loss of one maxillary implant occurred 3 years after implant
      exposure and 2 years after the provision of the implant-supported denture. In the
      second patient, after completion of growth and preceding bone augmentation,
      further implants facilitated an improved removable maxillary restoration. In both
      patients, an orthodontic alignment and reshaping of the conical anterior teeth by
      means of resin or full-ceramic crowns was applied to improve the esthetic
      appearance. Patients with HED require a consistent lifelong attendance comprised
      of oral hygiene, denture maintenance, and refitting. In oligo-/anodont children,
      the placement of implants in selected regions may be useful for the enhancement
      of denture retention. However, due to poor bone quality and volume, implant
      failure may occur.

PMID- 30192348
TI  - Full-Mouth Rehabilitation with Bone-Level Implant Guide and Monolithic Zirconia
      Prosthesis for Fibular Free Flap Reconstruction: A Case History Report.
AB  - The fibular free flap (FFF) approach is the preferred option for reconstruction
      of segmental mandibular deficiencies. Fixed dental prostheses are recommended for
      patients who have undergone FFF jaw surgery to improve quality of life, but
      treatment of these patients with an implant-supported prosthesis is challenging
      because of the thin bone and thick soft tissue in the fibula. This case history
      reports the use of a bone-level implant guide fabricated with a computer-aided
      system and milled customized long abutments for implant placement and
      prosthodontic procedures. Advanced digital technologies can facilitate jaw
      rehabilitation in patients with bone flap.

PMID- 30192349
TI  - Evolution of Topics in Maxillofacial Prosthetics Publications.
AB  - PURPOSE: To study the evolution of recent topics in maxillofacial prosthetics
      (MP) research. MATERIALS AND METHODS: Science mapping analyses were used to
      measure bibliometric similarities among articles extracted from the Web of
      Science from the last three decades. RESULTS AND CONCLUSION: Keyword co
      occurrence highlighted the rise of computer-aided design/computer-assisted
      manufacturing, mandibular reconstruction, and extraoral prostheses during the
      last decade. Citation analysis showed that surgery journals kept the leadership
      on MP publications, but that prosthodontics journals were closing the gap. The
      United States was the leading country in MP publications over the last three
      decades, but their lead is fast dissolving worldwide.

PMID- 30192350
TI  - Mechanical Study of Optimal Implant Position for Maxillary Implant-Supported
      Overdentures Using Three-Dimensional Simulation Software.
AB  - PURPOSE: The purpose of this study was to determine the optimal positioning of
      implants for maxillary implant-supported overdentures (MIODs) using finite
      element analysis (FEA). MATERIALS AND METHODS: Three-dimensional (3D) finite
      element models were built incorporating the maxilla, mucous membrane, removable
      denture, and artificial teeth using FEA software. Four models were prepared: one
      without an implant; one with two implants in the region of the lateral incisor;
      one with two implants in the first premolar region; and one with four implants in
      the lateral incisor and first premolar regions. Occlusal load was applied to the
      model, and denture displacement and the distribution of stress in the surrounding
      bone and mucous membrane were observed and measured. RESULTS: The maximum
      equivalent stresses to the bone and mucous membrane were highest in the premolar
      and anterior areas, respectively. Stress to the bone was concentrated around the
      implants, whereas stress in the mucous membrane was concentrated along the
      posterior margin. Denture displacement in the anterior direction was highest in
      the model without implants, while denture displacement in the posterior direction
      was less affected by the presence of implants. Overall, denture displacement in
      the four-implant model was smaller than that in the other models. Implant angle
      affected the stress distribution, with highest stress to the bone when the
      implant was positioned in a palatal direction and highest stress to the mucous
      membrane when placed mesially. However, implant angle had little impact on
      denture displacement, with almost the same stress for implants at all tested
      angles. CONCLUSION: Optimal implant position can stabilize overdentures and
      reduce stress to the bone and mucous membrane. Stress is reduced when implants
      are inserted in the premolar area and when the direction of the implant is
      perpendicular to the occlusal plane.

PMID- 30192351
TI  - Evaluation of Sexual, Physical, and Emotional Abuse in Women Diagnosed with
      Temporomandibular Disorders: A Case-Control Study.
AB  - PURPOSE: To compare the prevalence of physical and sexual abuse in women with
      temporomandibular disorders (TMD) vs women without TMD. METHODS: Forty women (age
      range 16-45 years) with idiopathic TMD were selected from the Occlusion Clinic at
      the Pontifical Catholic University of Rio Grande do Sul Faculty of Dentistry and
      were compared to 40 TMD-free women within the same age range. The Research
      Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) Axes I and II and
      the Sexual Abuse History Questionnaire (S/PAHQ) were used to collect data.
      RESULTS: Women with TMD diagnosed with myofascial pain had higher levels of
      chronic pain grade, disability points, chronic pain intensity, depression, and
      nonspecific physical symptoms with and without pain (ie, somatization). Women
      with TMD were significantly less educated, had lower family income, and were
      older than women without TMD. They also had significantly older partners, but
      there were no differences in the partners' occupation or education levels.
      Regarding emotional abuse, women with TMD reported significantly more insults and
      diminishing/humiliation in front of other people than the controls. The
      prevalence of physical and sexual abuse was higher in the TMD group, but this
      difference was nonsignificant. CONCLUSION: Emotional abuse, more than physical
      and sexual abuse, is an important risk factor for the development of TMD, even
      when controlling for education level, income, age, ethnicity, marital status, and
      occupation. Emotional abuse, as well as physical and sexual violence, should be
      assessed routinely in women suffering from chronic TMD.

PMID- 30192352
TI  - Polymer-Infiltrated-Ceramic-Network, CAD/CAM Restorations for Oral Rehabilitation
      of Pediatric Patients with X-Linked Ectodermal Dysplasia.
AB  - Functional and esthetic oral rehabilitation of young patients affected by
      ectodermal dysplasia is traditionally performed with direct composite
      restorations, which encounter various limitations. However, recent advances in
      computer-aided design/computer-assisted manufacturing (CAD/CAM) composites have
      led to the introduction of high-performance materials. In the present case
      report, a 9-year-old patient was treated with 20 CAD/CAM partial and peripheral
      restorations in polymer-infiltrated-ceramic-network material to restore deciduous
      and permanent teeth. The restorations were minimally invasive, since they did not
      require any tooth tissue preparation. Appropriate occlusal relationships with
      increased vertical dimension of occlusion were obtained. Tooth anatomy and
      esthetics were significantly improved, and chairtime was reduced.

PMID- 30192354
TI  - Digital Impression-Taking Facilitates Prosthetic Rehabilitation of Microstomia
      Patients: A Case History Report.
AB  - In most cases, prosthetic rehabilitation of patients suffering from microstomia
      is inconvenient for the patient and challenging for both the dentist and dental
      technician. In such cases, conventional impression-taking requires an
      individualized tray design and modified impression techniques, amplifying the
      risk for impression and cast deformation and thereby compromising the final
      outcome. An intraoral scanner (IOS) might overcome these limitations due to its
      reduced size compared to an impression tray. In the present case history report,
      a microstomia patient was successfully restored with a telescopic prosthesis by
      digitizing both retaining teeth and the palate with an IOS.

PMID- 30192353
TI  - Metamerism of Three Different Pigments for Facial Prostheses and a Method to
      Improve Shade Evaluation.
AB  - PURPOSE: To assess the illuminant metamerism of three different pigments used for
      maxillofacial prostheses under three different illumination sources and to
      standardize subjective shade-matching and observation protocols. MATERIALS AND
      METHODS: Nine silicone shade tabs were constructed for three volunteers who had
      light, medium, and dark skin tones using make-up, oil paint, or silicone pigments
      (three shade tabs per volunteer). A shade recipe was recorded during session one,
      and further tabs were constructed by following the recipe at two subsequent
      sessions. Using an observation protocol, expert examiners rated the shade match
      under three different illuminants. RESULTS: The intra-rater and inter-rater
      reliability revealed acceptable reliability (ICC > 0.6). Two-way analysis of
      variance revealed significant differences (P < .05) for pigments and illuminants
      and for the interaction of pigments with illuminant on the raters' scores.
      CONCLUSION: Illuminant metamerism affected the appearance of the silicone shade
      tabs. Oil paint with fluorescent or incandescent illumination had the worst
      effect. It was found possible to construct a consistent shade guide and to
      recommend an observation protocol, which should be repeatable if similarly
      experienced examiners are used.

PMID- 30192355
TI  - Light-activatable Chlorin e6 (Ce6)-imbedded erythrocyte membrane vesicles
      camouflaged Prussian blue nanoparticles for synergistic photothermal and
      photodynamic therapies of cancer.
AB  - Multiple therapeutic modalities, such as photodynamic (PDT) and photothermal
      (PTT) therapies, have been jointly applied to produce a synergistic effect for
      tumor eradication based on the hyperthermia and generation of reactive oxygen
      species (ROS) mediated by photoactive agents. Effective delivery of highly
      efficient photosensitizers and photothermal agents is the key for combination of
      PDT/PTT. Herein, we propose a strategy to functionalize Prussian blue (PB)
      nanoparticles (NPs) with Chlorin e6 (Ce6)-imbedded erythrocyte membrane vesicles.
      This nanoplatform can address the major issues of these two capable photoactive
      agents, such as limited biocompatibility, lack of functional chemical groups, and
      poor bioavailability due to rapid blood clearance or self-aggregation.
      Specifically, PB NPs were packaged within Ce6-imbedded erythrocyte membrane
      vesicles, named as PB@RBC/Ce6 NPs, to take advantage of both biological functions
      of natural erythrocyte membranes and the unique physicochemical properties of
      synthetic nanoagents. Compared to bare PB NPs or free Ce6, PB@RBC/Ce6 NPs
      exhibited considerably enhanced cellular uptake and accumulation in tumoral
      tissues. Moreover, the PB@RBC/Ce6 NP-mediated PDT/PTT combination therapies
      produced a notable effect in boosting the necrosis and late apoptosis of tumor
      cells in vitro, and further showed a synergistic therapeutic effect against an
      orthotopic tumor model in vivo.

PMID- 30192356
TI  - Deprotonation of a formato ligand by a cis-coordinated carbyne ligand within a
      bis(phenolate) tungsten complex.
AB  - Deprotonation of a formato ligand by a cis-coordinated propylidyne ligand in a
      tungsten(vi) complex [(OSSO)W([triple bond, length as m-dash]CEt)(OCHO)] (3) that
      contains a tetradentate bis(phenolato) ligand (OSSO = {1,4-dithiabutanediyl-2,2'
      bis(4,6-di-tert-butyl-phenolato)}) gave the dioxo complex [(OSSO)WO2] (4) along
      with CO, ethylene and propylene as major products of decomposition.

PMID- 30192357
TI  - A microfluidic platform for lifelong high-resolution and high throughput imaging
      of subtle aging phenotypes in C. elegans.
AB  - Aging produces a number of changes in the neuronal structure and function
      throughout a variety of organisms. These aging-induced changes encompass a wide
      range of phenotypes, from loss of locomotion ability to defective production of
      synaptic vesicles. C. elegans is one of the primary systems used to elucidate
      phenotypes associated with aging processes. Conventional aging studies in C.
      elegans are typically labor-intensive, low-throughput, and incorporate
      fluorodeoxyuridine (FUdR) as a sterilizing agent to keep the population age
      synchronized throughout the assay. However, FUdR exposure induces lifespan
      extension, and can potentially mask the phenotypes associated with the natural
      aging process. In addition, studying cellular or subcellular structures requires
      anesthetics or adhesives to immobilize nematodes while acquiring high-resolution
      images. In this platform, we are able to maintain a population (~1000 worms) age
      synchronized throughout its lifespan and perform a series of high-resolution
      microscopy studies in a drug-free environment. The device is composed of two main
      interconnected sections, one with the purpose of filtering progeny while keeping
      the parent population intact, and one for trapping nematodes in individual
      compartments for microscopy. Immobilization is carried out by decreasing the
      temperature of the device where nematodes are trapped by placing a heat sink on
      top of the chip. We were able to perform periodic high-resolution microscopy of
      fluorescently tagged synapses located at the dorsal side of the nematode's tail
      throughout the worms' lifespan. To characterize the subtle phenotypes that emerge
      as nematodes age, computer vision was implemented to perform automated unbiased
      detection of synapses and quantitative analysis of aging-induced synaptic
      changes.

PMID- 30192358
TI  - A rapidly recoverable shape memory polymer with a topologically well-controlled
      poly(ethyl methacrylate) structure.
AB  - Many of the unique properties of a conventionally crosslinked shape memory
      network are not found at the same time, and this is a large challenge for the
      development of advanced shape memory functional materials. In this work, a
      topologically well-controlled network shape memory poly(ethyl methacrylate) (CN
      SMPEMA) is designed and fabricated by introducing two tetra-armed functional
      structures simultaneously as well-defined structure units to promote switch
      segment and net-point uniform distribution via the combined technology of the
      unique controllable atom transfer radical polymerization (ATRP) and copper(i)
      catalyzed azide-alkyne cycloaddition (CuAAC). Compared with conventionally
      crosslinked networks, the as-prepared CN-SMPEMA not only exhibits a combination
      of excellent mechanical properties, shape fixity, shape recovery ratios and
      outstanding cycling stability, but also displays rapid recoverability.
      Additionally, a feasible molecular mechanism for the shape memory effect of the
      CN-SMPEMA system is analyzed and proposed. We anticipate that such a
      topologically well-defined network shape memory material with multiple excellent
      properties will broaden the practical application range of acrylate-based shape
      memory polymer materials.

PMID- 30192359
TI  - The Role of the Telovelar Approach in Fourth Ventricular Surgery: A New
      Perspective.
AB  - AIM: To evaluate the efficiency of the telovelar approach for fourth ventricular
      lesions through identifying and preserving neurovascular structures. MATERIAL AND
      METHODS: A total of 40 patients with fourth ventricular tumors were treated via
      the telovelar approach between 2005 and 2014. RESULTS: The telovelar approach
      provided adequate exposure in all patients. The brainstem and posterior inferior
      cerebellar artery (PICA) were identified early and preserved in all patients.
      Potential tumor attachment was observed at the floor of the fourth ventricle in
      22 (55%) patients: five had brainstem glioma, while 16 of the remaining 17 (94%)
      had focal attachments at any area of the caudal fourth ventricular floor, and two
      (11.7%) had attachments at any area of the lateral aspect of the rostral fourth
      ventricular floor, which was the only point of attachment in one. None of these
      tumors infiltrated the area of the cerebral aqueduct. Gross total excision was
      achieved in 45% of patients and near total excision was possible in 25% due to
      focal tumor attachment at one or more of the previously mentioned areas. However,
      debulking was possible in 30%. CONCLUSION: The telovelar approach provides the
      advantages of early identification and preservation of the brainstem and PICA,
      and allows for assessment of potential tumor attachment at the aforementioned
      areas. This is in contrast to the traditional consideration of vermian
      preservation, which is impossible to achieve regardless of the approach in
      patients with large tumors infiltrating the vermis. The pathological nature of
      the tumor and the degree of brainstem infiltration were key factors that
      determined the degree of tumor excision.

PMID- 30192360
TI  - Evaluation of Morphologic and Morphometric Characteristic of Foramen
      Transversarium on 3-Dimensional Multidetector Computed Tomography Angiography.
AB  - AIM: To investigate the size and variations of the foramen transversarium (TF).
      In addition, to study the anatomical variations of the vertebral artery entering
      the transverse foramen of the cervical vertebrae. MATERIAL AND METHODS: The
      images of 141 (90 males, 51 females) patients aged 18-79 years (mean: 52.7 years)
      were analyzed. As a result, 987 cervical spines (C1-C7) and 1974 foramina
      transversaria were individually evaluated. Each TF"s anterior-posterior (AP) and
      transverse diameter (T) was measured bilaterally from multidetector computed
      tomography (CT) images. The absence of TF was considered as agenesis and a
      diameter of less than 2 mm as hypoplastic. Double foramina and incomplete double
      foramina were also noted. We evaluated the levels at which the vertebral arteries
      entered the transverse foramina. RESULTS: The most frequent variation was
      duplication of TF, which was noted in a total of 88 (8.91%) cervical vertebrae.
      Agenesis of TF was seen in 37 (3.74%), and hypoplasia of TF in 26 (2.63%)
      cervical vertebrae. The vertebral artery entered into the transverse foramen of
      the 5th cervical vertebra from both sides in 4 (1.84%) patients. The vertebral
      artery entered into the transverse foramen of the 7th cervical vertebra in 4
      (1.84%) patients. The vertebral artery entered into the transverse foramen of the
      4th cervical vertebra in only 1 (0.45%) patient. CONCLUSION: We believe that the
      determination of foraminal variations could be an important guide for
      neurosurgeons and radiologists in the diagnosis and treatment of diseases in this
      area.

PMID- 30192361
TI  - Assessment of the MRI and Behavioral Test Results in a Focal Cerebral Ischemia
      Reperfusion Model in the Rat after Separate and Combined Use of Mouse-Derived
      Neural Progenitor Cells, Human-Derived Neural Progenitor Cells and Atorvastatin.
AB  - AIM: To assess the efficacy of Neural progenitor cell (NPC) transplantation in
      ischemic stroke, and to investigate whether atorvastatin enhances therapeutic
      potency of NPC after stroke. MATERIAL AND METHODS: The focal cerebral ischemia
      reperfusion model was performed by transient occlusion of middle cerebral artery.
      Rats were assigned randomly to receive intracerebral transplantation of mouse NPC
      alone (mNPC), human NPC alone (hNPC), mouse NPC plus oral atorvastatin (mNPC+A),
      human NPC plus oral atorvastatin (hNPC+A), oral atorvastatin alone, or
      intracerebral Dulbecco"s Modified Eagle"s medium injection (control group).
      Adhesive removal, rotarod, cylinder tests, and magnetic resonance imaging (MRI)
      were used for assessment of rats during 4 weeks. After sacrification on 28th day,
      rats were investigated by immunofluorescent staining. RESULTS: The hNPC and mNPC
      groups showed significantly improved functional outcome and reduced infarct area
      ratio compared with the control group. The hNPC group had significantly better
      performance and lower infarct area ratio than the mNPC group. Addition of
      atorvastatin to stem cell therapy significantly improved functional outcome,
      although it did not affect the infarct area ratio on MRI. Anti-inflammatory
      response in the infarct area was higher in the mNPC group. NPC transplantation
      significantly reduced the amount of microglia and a significant increase in the
      amount of astrocytes. CD8a+ T lymphocyte and granzyme B activities were not
      detected in any of the subjects. CONCLUSION: Both hNPC and mNPC treatments
      significantly improved functional outcome, and reduced infarct area ratio after
      stroke. Atorvastatin enhanced the therapeutic potency of NPCs, including
      neurological improvement.

PMID- 30192362
TI  - The Causes of Postoperative Meningitis: The Comparison of Gram-Negative and Gram
      Positive Pathogens.
AB  - AIM: To determine the microbiological etiology in critically ill neurosurgical
      patients with nosocomial meningitis (NM) and to show the impact of Gram-negative
      rods and the differences between patient characteristics and the clinical and
      prognostic measures in Gram-negative and Gram-positive meningitis. MATERIAL AND
      METHODS: In this prospective, single-center study, we reviewed all adult patients
      hospitalized during a 12-year period and identified pathogens isolated from post
      neurosurgical cases of NM. Demographic, clinical, and treatment characteristics
      were noted from the medical records. RESULTS: Of the 134 bacterial NM patients,
      78 were male and 56 were female, with a mean age of 46+/-15.9 and a median age of
      50 (18-80) years. One hundred and forty-one strains were isolated; 82 (58.2%)
      were Gram-negative, 59 (41.8%) were Grampositive. The most commonly isolated
      microorganism was Acinetobacter baumannii (34.8%). Comparison of mortality data
      shows that the patients who have meningitis with Gram-negative pathogens have
      higher mortality than with Gram-positives (p=0.034). The duration between surgery
      and meningitis was shorter in Gram-negative meningitis cases compared to others
      (p=0.045) but the duration between the diagnosis and death was shorter in Gram
      positive meningitis cases compared to Gram-negatives (p=0.017). Cerebrospinal
      fluid protein and lactate levels were higher and glucose level was lower in cases
      of NM with Gram-negatives (p values were respectively, 0.022, 0.039 and 0.049).
      CONCLUSION: In NM, Gram-negative pathogens were seen more frequently; A. baumanni
      was the predominant pathogen; and NM caused by Gram-negatives had worse clinical
      and laboratory characteristic and prognostic outcome than Gram-positives.

PMID- 30192363
TI  - Clinical Comparison Between Patients Operated for Unilateral Radiculopathy via a
      Contralateral (Facet-Sparing) and Ipsilateral Side Approach.
AB  - AIM: To compare clinical outcomes of the patients operated from the contralateral
      or ipsilateral side for unilateral radiculopathy in spinal stenosis. MATERIAL AND
      METHODS: This was a retrospective study. Twenty patients were listed as Group 1
      (Contralateral) with unilateral radiculopathy and spinal stenosis with/without
      lateral recess syndrome or foraminal stenosis. Decompression from opposite side
      of radiculopathy was performed to Group 1 patients. Decompression from the
      radiculopathy side was performed to the patients in Group 2 (Ipsilateral). Twenty
      eight patients were listed as Group 2. Back pain visual analogue scale (VAS)
      score and leg pain VAS score were assessed at preoperative, postoperative 1st
      month and postoperative 12th month. The results were compared statistically.
      RESULTS: Two patients were excluded because of reoperation at the 2nd month from
      the Group 2 to assessment 12th month VAS score. There was no significant
      difference between two groups at 1st month back pain VAS and leg pain VAS scores.
      There was no significant difference between two groups at 12th month back pain
      VAS and leg pain VAS scores. Dynamic stabilization was performed at 2nd month to
      two patients after the first operations for instability. So, there was no
      difference in clinical outcomes between the patients treated by contralateral
      approach and ipsilateral approach when instability did not occur. However, there
      is a risk of instability of the same side approach and surgery owing to shaving
      of the facet joint. CONCLUSION: In the contralateral approach, the recess of the
      contralateral side and foramen can be better seen than in the ipsilateral
      approach. So, this is a facet-sparing approach to spinal stenosis with/without
      lateral recess syndrome or foraminal stenosis with unilateral radiculopathy. The
      contralateral approach to unilateral radicular complaints is quite effective.
      With this approach, facet joints are protected from possible instability.

PMID- 30192364
TI  - Effects of Intrathecal Caffeic Acid Phenethyl Ester (CAPE) on IL-6 and TNF
      &alpha; Levels and Local Inflammatory Responses in Spinal Cord Injuries.
AB  - AIM: To investigate the effects of intrathecal caffeic acid phenethyl ester
      (CAPE) on tissue and serum interleukin-6 (IL-6) and tumor necrosis factor-alpha
      (TNF-?) levels following spinal cord injury (SCI) as well as its effects on edema
      and microhemorrhage. MATERIAL AND METHODS: Forty rats were divided into four
      groups. The sham group underwent single-level laminectomy and then received an
      intrathecal injection of isotonic saline. The control group received an
      intrathecal injection of isotonic saline following SCI induction. The
      methylprednisolone (MP) group received a single dose of MP intrathecally
      following SCI. The CAPE group received a single dose of CAPE intrathecally
      following SCI. IL-6 and TNF-? levels were determined using the enzyme-linked
      immunosorbent assay (ELISA) method. Spinal cord samples were evaluated
      histopathologically. RESULTS: The decrease in IL-6 levels in the CAPE group was
      significantly higher than that in the sham and control groups. However, this
      decrease was not as significant as that in the MP group. No significant decrease
      was identified in TNF-? levels. A significant decrease was observed in spinal
      cord edema and microhemorrhage in the CAPE group. A decrease in edema was
      observed in the MP group, but no effect was observed on microhemorrhage.
      CONCLUSION: Intrathecal CAPE administration following SCI decreases tissue and
      serum IL-6 levels as well as decreases spinal cord edema and microhemorrhage.

PMID- 30192365
TI  - Nerve Grafting versus Common Infraclavicular Intraplexal Nerve Transfer in Elbow
      Flexion Restoration.
AB  - AIM: To compare the results of nerve grafting versus common infraclavicular
      intraplexal nerve transfer in elbow flexion restoration. MATERIAL AND METHODS:
      The study included 39 patients with upper brachial plexus palsy who were operated
      using common intraplexal nerve transfer (Oberlin procedure) and the thoracodorsal
      and medial pectoral nerve transfer to the musculocutaneous nerve or grafting of
      C5 to the musculocutaneous nerve, for elbow flexion restoration. All patients
      underwent detailed preoperative evaluation, which included clinical and
      neurological examinations, electrophysiological investigation and
      neuroradiological studies. The final evaluation of achieved recovery of elbow
      flexion was done two years after surgery, using the British Medical Council
      scale. RESULTS: We achieved functional satisfactory recovery (M3, M4, M5) in 29
      of 30 patients (96.7%) in the common intraplexal nerve transfer group, and in 4
      of 9 patients in the nerve grafting group (44.4.%). There was a significant
      statistical difference between these two groups in favor of common intraplexal
      nerve transfers over C5 grafting to the musculocutaneous nerve regarding
      functional recovery. CONCLUSION: The results of our study concur with the
      findings of previous studies favoring intraplexal nerve transfers over nerve
      grafting in the restoration of elbow flexion in upper brachial plexus palsy. They
      reveal that intraplexal nerve transfers are clearly the primary treatment
      modality in cases of upper brachial plexus palsy without any sign of viable
      proximal C5 stump presence, while in cases of upper brachial plexus palsy with
      signs of viable proximal C5 stump the choice of the best treatment modality is
      still controversial.

PMID- 30192366
TI  - The Effects of Proanthocyanidin on Vasospasm After Experimental Subarachnoidal
      Hemorrhage in Rats.
AB  - AIM: Delayed ischemic neurological deficit (DIND) and cerebral vasospasm (CV)
      remain the most common and debilitating neurological complications following
      aneurysmal subarachnoidal hemorrhage (SAH). Many reports demonstrate the
      importance of proanthocyanidins (PR) on the vascular system, including
      endothelium-dependent relaxation of blood vessels. These effects of PR on the
      cerebral vascular system were examined in this study. < p < MATERIAL and METHODS:
      Fifty-two adult Sprague-Dawley male rats were used for the experimental double
      hemorrhage model. They were divided to control, sham, pre- and post
      interventional treatment groups. 100 mg/kg PR was administered for the treatment
      for respect to groups. Basilar artery diameter (BAD) and arterial wall thickness
      were measured and the apoptosis ratio of the endothelial cells was calculated.
      Arterial walls were examined electron microscopically (EM). RESULTS: There were
      significant differences between the groups except control and pre-SAH (p=0.37)
      and post-SAH and pre- SAH groups (p=0.15) with respect to BAD. According to
      arterial wall thickness, apoptosis ratio, and grading, there were significant
      differences between the groups except control and pre-SAH (p=0.85, p=0.49 and
      p=0.18 respectively) and SAH and post-SAH (p=0.08, p=0.21 and p=0.24
      respectively) groups. EM findings revealed that pro-apoptotic and pro-necrotic
      degenerated endothelial cells with seldom vacuolization in post-SAH treatment
      group which were more serious in SAH group. CONCLUSION: Pre-SAH administration of
      PR induces better vasodilatation and protection of basilar artery (BA) from
      vasospasm (VS), which could yield neuroprotective and vasodilatator effects. In
      addition, PR appears to be involved in relieving oxidative damage, with an
      antioxidant-antiapoptotic-antinecrotic effect that may contribute to vascular
      dilation.

PMID- 30192367
TI  - Ligamentum Flavum Buckling Causing Immediate Post-Operative Neurological
      Deterioration After an Anterior Cervical Discectomy: Case Report.
AB  - Neurological injury is a potential complication of anterior cervical discectomy
      (ACDF). Iatrogenic trauma, hypoxic-ischemic damage during surgery or epidural
      hematoma could cause neurological deterioration after surgery. This is the first
      case being reported of neurological deterioration after an anterior cervical
      discectomy due to ligamentum flavum buckling. The case illustrated an uncommon
      cause of cord compression after ACDF. Therefore, ligamentum flavum buckling
      should be considered as one of the potential causes for acute neurologic
      deterioration after an anterior cervical discectomy. While keeping this rare
      complication in mind, obtaining a quick post-operative imaging seems mandatory in
      early detection and establishing an appropriate management.

PMID- 30192368
TI  - Complications of 2-Level Dynamic Stabilization: A Correlative Clinical and
      Radiological Analysis at Two-Year Follow-up on 103 Patients.
AB  - AIM: To investigate the postoperative complications, such as screw loosening,
      screw breakage and adjacent segment disease (ASD), in patients who underwent
      surgery with 2-level dynamic stabilization systems. MATERIAL AND METHODS:
      Postoperative complications, clinical improvements and radiological parameters in
      patients who underwent surgery using a dynamic system for 2-level lumbar
      stabilization were retrospectively reviewed. A total of 103 patients with lumbar
      degenerative spinal instability underwent 2-level dynamic stabilization. Clinical
      findings were reviewed at 2-year followup. Screw breakage and loosening were
      evaluated during this duration together with clinical findings. RESULTS: Visual
      analog scale (VAS) and Oswestry Disability Index (ODI) scores were significantly
      decreased at the four-month evaluation, and they were also decreased at the 1
      year follow up and at the 24th postoperative month. ASD was diagnosed in twelve
      (8 females, 4 males) of the 103 patients in the follow-up radiological and
      clinical controls. There were 9 screw breakages and 4 screw loosening cases. The
      complication rate of 2-level dynamic stabilization was high in this study.
      CONCLUSION: Our results showed that complications (screw loosening or breakage
      and adjacent segment disease) are not rare after 2-level dynamic stabilization,
      unlike the acceptable results with the single-level dynamic system. The most
      probable explanation is that the instrument system behaves more rigidly with
      every additional segment.

PMID- 30192369
TI  - There is No Remarkable Difference Between Pedicle Screw and Hybrid Construct in
      the Correction of Lenke Type-1 Curves.
AB  - AIM: To compare the deformity correction success of segmental pedicle screw and
      hybrid instrumentation for the treatment of Lenke type-1 adolescent idiopathic
      scoliosis (AIS) curves. MATERIAL AND METHODS: Surgically treated Lenke type-1
      scoliosis patients were retrospectively evaluated and data of 26 patients treated
      with hybrid instrumentation were included in the first group. In this group, all
      patients had been operated with hooks at the thoracic part and transpedicular
      screws at the lumbar part. The second group included 26 patients operated with
      all segment transpedicular screws. Cobb angles of curves, flexibility, apical
      vertebral translation (AVT), coronal body balance, kyphosis and lordosis were
      measured. All measurements and correction ratios were compared between the
      groups. RESULTS: There were no significant differences between the two groups for
      preoperative thoracic and lumbar Cobb angles, thoracic and lumbar curve
      flexibility, coronal balance, AVT, kyphosis and lordosis. However, the
      postoperative thoracic correction ratio was significantly different between the
      two groups. CONCLUSION: Segmental screw instrumentation had better results for
      thoracic curve correction than hybrid instrumentation for the treatment of Lenke
      type-1 curves. Good results may be achieved with both techniques to provide
      sagittal balance.

PMID- 30192370
TI  - Genetic structure and sex-biased gene flow in the history of southern African
      populations.
AB  - OBJECTIVES: We investigated the genetic history of southern African populations
      with a special focus on their paternal history. We reexamined previous claims
      that the Y-chromosome haplogroup E1b1b (E-M293) was brought to southern Africa by
      pastoralists from eastern Africa, and investigated patterns of sex-biased gene
      flow in southern Africa. MATERIALS AND METHODS: We analyzed previously published
      complete mtDNA genome sequences and ~900 kb of NRY sequences from 23 populations
      from Namibia, Botswana, and Zambia, as well as haplogroup frequencies from a
      large sample of southern African populations and 23 newly genotyped Y-linked STR
      loci for samples assigned to haplogroup E1b1b. RESULTS: Our results support an
      eastern African origin for Y-chromosome haplogroup E1b1b (E-M293); however, its
      current distribution in southern Africa is not strongly associated with
      pastoralism, suggesting more complex demographic events and/or changes in
      subsistence practices in this region. The Bantu expansion in southern Africa had
      a notable genetic impact and was probably a rapid, male-dominated expansion. Our
      finding of a significant increase in the intensity of the sex-biased gene flow
      from north to south may reflect changes in the social dynamics between Khoisan
      and Bantu groups over time. CONCLUSIONS: Our study shows that the population
      history of southern Africa has been complex, with different immigrating groups
      mixing to different degrees with the autochthonous populations. The Bantu
      expansion led to heavily sex-biased admixture as a result of interactions between
      Khoisan females and Bantu males, with a geographic gradient which may reflect
      changes in the social dynamics between Khoisan and Bantu groups over time.

PMID- 30192371
TI  - The daily grind: Sex- and age-related activity patterns inferred from cross
      sectional geometry of long bones in a pre-Columbian muisca population from
      Tibanica, Colombia.
AB  - OBJECTIVES: Daily activities involve biomechanical strains acting on skeletal
      structures. This study identifies differences in activity patterns between males
      and females, and between young, middle, and older aged individuals within an
      excavated Muisca skeletal sample from the Eastern Andes region of Northern South
      America. MATERIALS AND METHODS: The Tibanica archaeological site (AD 1000-1400)
      is located at 2600 masl on the Sabana de Bogota, Colombia. Cross-sectional
      geometric analysis of femurs from 63 individuals and paired-humerii from 33
      individuals was used to examine bone size (TA), strength (J) and diaphyseal shape
      (Imax /Imin , Ix /Iy ). RESULTS: The findings indicate both age- and sex-related
      differences in activity patterns. An emphasis on upper body strength and
      robusticity was observed in the females, while males performed more strenuous
      work using their lower bodies, suggesting gender-based differences in labor. Men
      showed significant asymmetry in their humerii, with most showing right-hand
      dominance for upper body activities, while females showed high levels of humeral
      symmetry indicating similar levels of biomechanical stress for both arms. Female
      femoral diaphyseal shape changes with age, suggesting more mobility in youth and
      decreased mobility in middle and older ages. DISCUSSION: These results suggest
      that daily life may have been structured through patterns of routine labor that
      united and divided particular age and sex groups. Cross-sectional geometry data
      indicate women likely spent significant time and energy preparing food,
      especially grinding maize or other foods, while men may have done more long
      distance walking potentially to work in agricultural fields or procure other
      resources.

PMID- 30192372
TI  - Predicting the risk for aberrant opioid use behavior in patients receiving
      outpatient supportive care consultation at a comprehensive cancer center.
AB  - BACKGROUND: Opioid misuse is a growing crisis. Patients with cancer who are at
      risk of aberrant drug behaviors are frequently underdiagnosed. The primary
      objective of this study was to determine the frequency and factors predicting a
      risk for aberrant opioid and drug use behaviors (ADB) among patients who received
      an outpatient supportive care consultation at a comprehensive cancer center. In
      addition, the screening performance of the Cut Down-Annoyed-Guilty-Eye Opener
      (CAGE) questionnaire adapted to include drug use (CAGE-AID) was compared with
      that of the 14-item Screener and Opioid Assessment for Patients With Pain (SOAPP
      14) tool as instruments for identifying patients at risk for ADB. METHODS: In
      total, 751 consecutive patients with cancer who were referred to a supportive
      care clinic were reviewed. Patients were eligible if they had diagnosis of cancer
      and had received opioids for pain for at least 1 week. All patients were assessed
      using the Edmonton Symptom Assessment Scale (ESAS), the SOAPP-14, and the CAGE
      AID. SOAPP scores >=7 (SOAPP-positive) were used to identify patients who were at
      risk of ADB. RESULTS: Among the 729 of 751 (97%) evaluable consults, 143 (19.6%)
      were SOAPP-positive, and 73 (10.5%) were CAGE-AID-positive. Multivariate analysis
      revealed that the odds ratio of a positive SOAPP score was 2.3 for patients who
      had positive CAGE-AID scores (P < .0001), 2.08 for men (P = .0013), 1.10 per
      point for ESAS pain (P = .014), 1.13 per point for ESAS anxiety (P = .0015), and
      1.09 per point for ESAS financial distress (P = .012). A CAGE-AID cutoff score of
      1 in 4 had 43.3% sensitivity and 90.93% specificity for screening patients with a
      high risk of ADB. CONCLUSIONS: The current results indicate a high frequency of
      an elevated risk of ADB among patients with cancer. Men and patients who have
      anxiety, financial distress, and a prior history of alcoholism/illicit drug use
      are at increased risk of ADB.

PMID- 30192373
TI  - A Comparative Study Between Allometric Scaling and Physiologically Based
      Pharmacokinetic Modeling for the Prediction of Drug Clearance From Neonates to
      Adolescents.
AB  - The objective of this study was to compare the predictive performance of an
      allometric model with that of a physiologically based pharmacokinetic (PBPK)
      model to predict clearance or area under the concentration-time curve (AUC) of
      drugs in subjects from neonates to adolescents. From the literature, 10 studies
      were identified in which clearance or AUC of drugs from neonates to adolescents
      was predicted by PBPK models. In these published studies, drugs were given to
      children either by intravenous or oral route. The allometric model was an age
      dependent exponent (ADE) model for the prediction of clearance across the age
      groups. The predicted clearance or AUC values from the PBPK and ADE models were
      compared with the experimental values. The acceptable prediction error was the
      percentage of subjects within an 0.5- to 2-fold or 0.5- to 1.5-fold prediction
      error. There were 73 drugs with a total of 372 observations. From PBPK and
      allometric models, 91.1% and 90.6% of observations were within 0.5- to 2-fold
      prediction error, respectively. For children <=2 years old (n = 130), PBPK and
      allometric models had 89% and 87% of observations within the 0.5- to 2-fold
      prediction error, respectively. This study indicates that the predictive power of
      PBPK and allometric models was essentially similar for the prediction of
      clearance or AUC in pediatric subjects ranging from neonates to adolescents.

PMID- 30192374
TI  - Castration remains despite decreasing definitive treatment of localized prostate
      cancer in the elderly: A case for de-implementation.

PMID- 30192376
TI  - Evaluating age-related changes of some facial signs among men of four different
      ethnic groups.
AB  - BACKGROUND: The alterations of some facial characteristics, with age, in men of
      different ethnic groups are a scarcely studied topic. OBJECTIVE: To illustrate
      and grade, among men of four different ethnic descents (Asians, African
      Americans, Caucasians, Indians), aged 18-80 year, the changes in the severity of
      some facial signs occurring with age. METHODS: Digital Photographs (full face,
      profile, 45 degrees ) of 1058 subjects were taken under standard conditions of
      lightning. These allowed us to zoom in on 15-20 different facial signs on all
      subjects. Their observations by 15 trained experts, under calibrated screens,
      allowed these signs to be graded, with the help of four referential skin Atlases,
      specific to the gender and ethnic groups studied. RESULTS: Most facial signs show
      a rather regular increase with age, with different kinetics according to the
      ethnic group. The major changes, in all four ethnic groups, mostly concern skin
      structural alterations (wrinkles, neck sagging or texture). The changes in the
      severity of some wrinkles (forehead, inter-ocular...) may be viewed as ethnic
      signatures. The modifications in pigmentation disorders seem more closely linked
      to the constitutive skin pigmentation (photo-types), among which pigmentary spots
      are confirmed as a more specific Asian trait. CONCLUSION: Men of four different
      ethnic origins present different and ethnic-related facial alterations with
      increasing age, of different amplitudes.

PMID- 30192375
TI  - Genome-wide microRNA analysis of HPV-positive self-samples yields novel triage
      markers for early detection of cervical cancer.
AB  - Offering self-sampling for HPV testing improves the effectiveness of current
      cervical screening programs by increasing population coverage. Molecular markers
      directly applicable on self-samples are needed to stratify HPV-positive women at
      risk of cervical cancer (so-called triage) and to avoid over-referral and
      overtreatment. Deregulated microRNAs (miRNAs) have been implicated in the
      development of cervical cancer, and represent potential triage markers. However,
      it is unknown whether deregulated miRNA expression is reflected in self-samples.
      Our study is the first to establish genome-wide miRNA profiles in HPV-positive
      self-samples to identify miRNAs that can predict the presence of CIN3 and
      cervical cancer in self-samples. Small RNA sequencing (sRNA-Seq) was conducted to
      determine genome-wide miRNA expression profiles in 74 HPV-positive self-samples
      of women with and without cervical precancer (CIN3). The optimal miRNA marker
      panel for CIN3 detection was determined by GRridge, a penalized method on
      logistic regression. Six miRNAs were validated by qPCR in 191 independent HPV
      positive self-samples. Classification of sRNA-Seq data yielded a 9-miRNA marker
      panel with a combined area under the curve (AUC) of 0.89 for CIN3 detection.
      Validation by qPCR resulted in a combined AUC of 0.78 for CIN3+ detection. Our
      study shows that deregulated miRNA expression associated with CIN3 and cervical
      cancer development can be detected by sRNA-Seq in HPV-positive self-samples.
      Validation by qPCR indicates that miRNA expression analysis offers a promising
      novel molecular triage strategy for CIN3 and cervical cancer detection applicable
      to self-samples.

PMID- 30192377
TI  - Cost-savings of adalimumab in hidradenitis suppurativa: a retrospective analysis
      of a real-world cohort.
AB  - BACKGROUND: The introduction of adalimumab in the management of hidradenitis
      suppurativa (HS) raises questions regarding the cost-efficacy of treatment.
      OBJECTIVES: To explore cost-efficacy of treatment with anti-tumour necrosis
      factor (TNF) agents in a real-world cohort. METHODS: Patients with Hurley stage
      II and III HS with >= 1 year of follow-up and at least three visits per year from
      September 2003 to December 2016 were analysed. Patient visits were divided into
      two categories - visits for treatment with agents blocking TNF or visits for
      other therapies. The cost of exacerbations was calculated based on the cost of
      items provided in current price lists or by the national health insurance agency
      in cases of hospitalization. Effectiveness of anti-TNF agents was calculated by
      assessing containment of exacerbations. The primary study end point was the cost
      savings achieved using anti-TNF agents. RESULTS: Overall, 1211 patient visits for
      250 patients were analysed. Total containment of exacerbations was found in 25.1%
      of visits involving other therapies and in 63.4% of visits involving anti-TNF
      agents. The cost-savings per patient visit for patients receiving anti-TNF agents
      vs. other therapies was ?178.92. The odds ratio for the total containment of
      exacerbations among patients with Hurley stage II and III was 4.86 and 6.03,
      respectively (P = 0.466). Treatment with anti-TNF agents was an independent
      variable affecting annual cost as shown by two-way analysis of variance. In
      Hurley stage III HS, mean annual cost was ?8309.60 under other therapies compared
      with ?3264.20 using anti-TNF agents (P = 0.004). CONCLUSIONS: Treatment with anti
      TNF agents achieves significant cost-benefit through containment of HS
      exacerbations. The efficacy of anti-TNF agents was similar for both disease
      stages.

PMID- 30192378
TI  - A Phase 1, Multiple-Dose Study of Vedolizumab in Japanese Patients With
      Ulcerative Colitis.
AB  - Although previous studies have shown that patients with ulcerative colitis may
      benefit from treatment with vedolizumab, a humanized monoclonal antibody
      targeting the alpha4 beta7 integrin heterodimer, no data exist in Japanese
      populations. The aim of this phase 1, open-label, multicenter study was to assess
      the pharmacokinetics, pharmacodynamics, efficacy, and safety of vedolizumab in
      Japanese patients with ulcerative colitis. Adult patients with confirmed
      ulcerative colitis received either 150 mg (step 1) or 300 mg (step 2) of
      intravenous (IV) vedolizumab on days 1, 15, and 43 of the study protocol.
      Pharmacokinetic, pharmacodynamic, safety, and efficacy parameters were all
      assessed through study end (day 239). Nine patients were enrolled in this study
      (150 mg, n = 3; 300 mg, n = 6). Patients who received vedolizumab IV 300 mg had
      approximately twice the drug exposure of those receiving vedolizumab IV 150 mg
      (day 1 AUCday14 744 vs 408 MUg.d/mL) and a longer-lasting maximal saturation of
      alpha4 beta7 integrin (155 vs 99 days). The number of treatment-emergent adverse
      events, all of which were mild or moderate in intensity, was similar between the
      150-mg (15 events) and 300-mg (20 events) groups. The 2 patients (150 mg group)
      not in clinical remission by partial Mayo score at the start of the study met the
      criteria for clinical remission on days 15 and 155 of the study, respectively. In
      conclusion, in Japanese patients with ulcerative colitis, vedolizumab showed
      similar pharmacokinetic and pharmacodynamic results to those seen in non-Japanese
      patients. Vedolizumab was well tolerated and demonstrated clinical activity
      consistent with previous studies.

PMID- 30192379
TI  - A Pilot Observational Study of Environmental Summertime Health Risk Behavior in
      Central Brisbane, Queensland: Opportunities to Raise Sun Protection Awareness in
      Australia's Sunshine State.
AB  - Melanoma skin cancer rates in Queensland exceed the national Australian incidence
      rate, which together with New Zealand are recognized as the world's highest.
      Incidence is especially high among younger members of the population. In this
      study, the sun-protective behaviors of urban Queenslanders (n = 752) going about
      their day-to-day activities during a midweek noon time hourly period were
      observed on a summer's day in central Brisbane (27.47 degrees S, 153.03 degrees
      E), Australia. Observed sun protection practices were poor, given the time of
      year and peak solar noon period of the study. More individuals (n = 249; 33.1%)
      were seen wearing sunglasses than a hat (n = 101; 13.4%). Ninety-three
      individuals were actively engaging with mobile phones (phone in hand). A further
      231 individuals (30.7%) were observed with a mobile phone on them. Opportunities
      to modify group behavior based on mobile phone sun protection notifications and
      to engage with "at risk" members of the Queensland population are considered from
      the variable codependencies examined in this study, including the influence of
      social group size, observed sun protection and mobile phone use. Our preliminary
      findings suggest that mobile phones provide an underutilized opportunity for
      delivering tailored skin cancer prevention messaging.

PMID- 30192380
TI  - Glucose metabolism in the brain in LMNB1-related autosomal dominant
      leukodystrophy.
AB  - OBJECTIVE: LMNB1-related autosomal dominant leukodystrophy is caused by an
      overexpression of the protein lamin B1, usually due to a duplication of the LMNB1
      gene. Symptoms start in 5th to 6th decade. This slowly progressive disease
      terminates with death. We studied brain glucose metabolism in this disease using
      18 F-fluorodeoxyglucose positron emission tomography (PET). METHODS: We examined
      8 patients, aged 48-64 years, in varying stages of clinical symptomatology. Two
      patients were investigated with quantitative PET on clinical indications after
      which six more patients were recruited. Absolute glucose metabolism was analyzed
      with the PVElab software in 6 patients and 18 healthy controls. A
      semiquantitative analysis using the CortexID software was performed in seven
      investigations, relating local metabolism levels to global glucose metabolism.
      RESULTS: The clinical quantitative PET revealed low global glucose metabolism,
      with the most marked reduction in the cerebellum. In the PVElab analysis,
      patients presented low mean glucose metabolism in the cerebellum, brainstem and
      global grey matter. In the semiquantitative analysis, 2 patients showed a
      decreased metabolism in the cerebellum and 4 patients a relatively higher
      metabolism in parts of the temporal lobes. Since none of the patients showed an
      increased metabolism in the quantitative analysis, we interpret these increases
      as "pseudo-increases" related to a globally reduced metabolism. CONCLUSIONS:
      Global reduction of grey matter glucose metabolism in this white matter disease
      most likely depends on a combination of cortical afferent dysfunction and, in
      later stages, neuronal loss. The lowest metabolism in the cerebellum is
      consistent with histopathological findings and prominent cerebellar symptoms.

PMID- 30192381
TI  - Proposition of a Minimal Effective Dose of Vigabatrin for the Treatment of
      Infantile Spasms Using Pediatric and Adult Pharmacokinetic Data.
AB  - Vigabatrin is an antiepileptic drug indicated as monotherapy in infantile spasms.
      However, the pharmacokinetic profile of this compound in infants and young
      children is still poorly understood, as is the minimal effective dose, critical
      information given the risk of exposure-related retinal toxicity with vigabatrin.
      A reasonable approach to determining this minimal dose would be to identify the
      lowest dose providing a low risk of exposure overlap with the 36-mg/kg dose,
      which is the highest dose associated with an increased risk for treatment
      failure, based on randomized dose-ranging data. A population pharmacokinetic
      model was consequently developed from 28 children (aged 0.4-5.7 years) for the
      active S(+)-enantiomer, using Monolix software. In parallel, a population model
      was developed from published adult data and scaled to children using theoretical
      allometry and maturation of the renal function. A one-compartment model with zero
      order absorption and first-order elimination described the pediatric data. Mean
      population estimates (percentage interindividual variability) for the apparent
      clearance, apparent distribution volume, and absorption duration were 2.36 L/h
      (24.5%), 17 L (38%), and 0.682 hours, respectively. Apparent clearance and
      apparent distribution volume were related to body weight by empirical allometric
      equations. Monte Carlo simulations evidenced that a daily dose of 80 mg/kg should
      minimize exposure overlap with the 36-mg/kg dose. Similar results were obtained
      for the adult model scaled to children. Consequently, a minimal effective dose of
      80 mg/kg/day could be considered for patients with infantile spasms.

PMID- 30192382
TI  - The incidence and outcomes of nurse bullying in the Russian Federation.
AB  - AIM: The aim of this study was to describe bullying experienced by professional
      nurses working in the Russian Federation. The frequency and type of bullying
      behaviours experienced, the personal and professional consequences of bullying
      and the actions taken to address bullying were all examined.
      BACKGROUND/INTRODUCTION: Workplace bullying negatively affects nurses, patients
      and healthcare organizations. To date, no research has been conducted on
      workplace bullying among nurses in the Russian Federation. METHODS: This was a
      descriptive study using survey methodology. Members of the Russian Nurses
      Association were invited to participate via email and social media. Participants
      completed the 26-item, web-based Bullying in the Workplace Survey. Data were
      analysed using descriptive statistics. RESULTS: Of the 438 participants, 63%
      reported being bullied at some point during their career. The majority were
      female and worked fulltime for an average of 20 years. Over half the nurses were
      working in staff positions when bullying occurred, and administrators were most
      commonly identified as the bully. Bullying caused moderate to severe distress in
      73.5%. Half of the nurses reported that bullying affected their work, and 83.3%
      reported that it affected their health. Just over 70% took action to address the
      bullying situation; 59% of those who did were dissatisfied with the outcome.
      CONCLUSION: Bullying is prevalent in the nursing workplace in the Russian
      Federation. The perpetrators were most frequently the nurse administrator or
      physician administrator. Workplace bullying negatively affects nurses' ability to
      function and subsequently impacts nursing teamwork and patient care. IMPLICATIONS
      FOR NURSING AND HEALTH POLICY: Identifying bullying, its antecedents and
      consequences in the Russian Federation are a requisite for developing meaningful
      interventions and contributing to shaping local and international policy.

PMID- 30192383
TI  - Afatinib plus bevacizumab combination after acquired resistance to EGFR tyrosine
      kinase inhibitors in EGFR-mutant non-small cell lung cancer: Multicenter, single
      arm, phase 2 trial (ABC Study).
AB  - BACKGROUND: Preclinical studies suggested that the addition of bevacizumab could
      overcome acquired resistance (AR) to epidermal growth factor receptor (EGFR)
      tyrosine kinase inhibitors (TKIs). The aim of this study was to evaluate the
      clinical efficacy and safety of a combination of afatinib and bevacizumab after
      AR. METHODS: Patients with EGFR-mutant non-small cell lung cancer after AR were
      enrolled during any line of therapy. Afatinib was prescribed at 30 mg, and 15
      mg/kg bevacizumab was administered every 3 weeks until progression. RESULTS:
      Between October 2014 and May 2017, 32 eligible patients were evaluated. The
      mutation subtypes were Del-19 (20 [63%]), L858R (11 [34%]), and L861Q (1 [3%]).
      T790M was detected in 14 patients (44%). The median number of prior regimens was
      4 (range, 1-10). Six patients obtained a partial response, and 23 had stable
      disease; this resulted in an objective response rate (ORR) of 18.8% (95%
      confidence interval [CI], 7.2%-36.4%) and a disease control rate of 90.7% (95%
      CI, 75.0%-98.0%). The median progression-free survival (PFS) was 6.3 months (95%
      CI, 3.9-8.7 months). The ORRs and median PFS times of T790M+ and T790M- patients
      were 14.3% and 22.2%, respectively, and 6.3 and 7.1 months, respectively; those
      of Del-19 and L858R patients were 20.0% and 11.1%, respectively, and 6.3 and 5.1
      months, respectively. Grade 3 or higher adverse events (incidence >= 10%)
      included paronychia (25%), hypertension (41%), and proteinuria (19%). There were
      no treatment-related deaths, interstitial lung disease, or bevacizumab-associated
      severe bleeding. CONCLUSIONS: Afatinib plus bevacizumab demonstrated clinical
      efficacy and safety after AR to EGFR TKIs and could be a therapeutic salvage
      option for T790M- populations.

PMID- 30192384
TI  - Optimistic, realistic, and pessimistic illness perceptions; quality of life; and
      survival among 2457 cancer survivors: the population-based PROFILES registry.
AB  - BACKGROUND: Threatening illness perceptions (IPs) have been associated with
      poorer health outcomes. However, to the authors' knowledge, it remains unclear
      whether threatening IPs that are consistent with disease severity are equally
      harmful. The aim of the current study was to: 1) identify subgroups of cancer
      survivors based on IPs and prognosis; and 2) assess the health-related quality of
      life (HRQOL) and survival associated with these subgroups. METHODS: The authors
      used survey data from the population-based Patient Reported Outcomes Following
      Initial treatment and Long term Evaluation of Survivorship (PROFILES) registry,
      which were collected between 2008 and 2015 and included 2457 cancer survivors who
      were <5 years after their cancer diagnosis (colon, rectal, prostate, endometrial,
      or ovarian cancer or non-Hodgkin lymphoma). Clinical and survival data were
      collected through the Netherlands Cancer Registry. Subgroups were defined by IPs
      (Brief Illness Perception Questionnaire) and prognosis (conditional 5-year
      relative survival) into survivors with 1) IPs consistent with prognosis
      ("realistic"); 2) less threatening IPs than expected based on prognosis
      ("optimistic"); and 3) more threatening IPs than expected based on prognosis
      ("pessimistic"). RESULTS: Compared with survivors with realistic IPs (1230
      survivors), those with optimistic IPs (582 survivors) were found to have a higher
      HRQOL (P < .01 on all European Organization for the Research and Treatment of
      Cancer Quality of Life Questionnaire Core 30 [EORTC QLQ-C30] scales) and a lower
      all-cause mortality (hazard ratio, 0.72; P < .01), whereas those with pessimistic
      IPs (645 survivors) had a lower HRQOL (P < .01 on all scales) and a higher all
      cause mortality (hazard ratio, 1.52; P < .01). CONCLUSIONS: Optimistic IPs are
      associated with better HRQOL and survival, even if they may appear to be
      unrealistic with respect to cancer survivors' prognosis. Survivors with
      pessimistic IPs appear to have the worst outcomes. Therefore, efforts are needed
      to provide better support to patients with pessimistic IPs to improve their
      outcomes. Cancer 2018;124:3609-17. (c) 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- 30192385
TI  - The addition of pretreatment plasma Epstein-Barr virus DNA into the 8th edition
      of nasopharyngeal cancer TNM stage classification.
AB  - The 8th edition of the American Joint Committee on Cancer (AJCC)/Union for
      International Cancer Control (UICC) stage classification (TNM) for nasopharyngeal
      carcinoma (NPC) was launched. It remains unknown if incorporation of non-anatomic
      factors into the stage classification would better predict survival. We
      prospectively recruited 518 patients with non-metastatic NPC treated with radical
      IMRT +/- chemotherapy based on the 8th edition TNM. Recursive partitioning
      analysis (RPA) incorporating pretreatment plasma EBV DNA derived new stage
      groups. Multivariable analyses to calculate adjusted hazard ratios (AHRs) derived
      another set of stage groups. 5-year progression-free survival (PFS), overall
      survival (OS) and cancer-specific survival (CSS) were: stage I (PFS 100%, OS 90%,
      CSS 100%), II (PFS 88%, OS 84%, CSS 95%), III (PFS 84%, OS 84%, CSS 90%) and IVA
      (PFS 71%, OS 75%, CSS 80%) (p < 0.001, p = 0.066, and p = 0.002 respectively).
      RPA derived 4 new stages: RPA-I (T1-T4N0-N2 & EBV DNA <500 copies/ml) (PFS 94%,
      OS 89%, CSS 96%), RPA-II (T1-T4N0-N2 & EBV DNA >=500 copies/ml) (PFS 80%, OS 83%,
      CSS 89%), RPA-III (T1-T2N3) (PFS 64%, OS 83%, CSS 83%) and RPA-IVA (T3-T4N3) (PFS
      63%, OS 60% and CSS 68%) (all with p < 0.001). AHR using covariate adjustment
      also yielded a valid classification (I: T1-T2N0-N2; II: T3-T4N0-N2 or T1-T2N3,
      and III: T3-T4N3) (all with p < 0.001). However, RPA stages better predicted
      survival for PS and CSS after bootstrapping replications. Our RPA-based stage
      groups revealed better survival prediction compared to the 8th edition TNM and
      the AHR stage groups. This article is protected by copyright. All rights
      reserved.

PMID- 30192386
TI  - Dose-Finding Studies Among Orphan Drugs Approved in the EU: A Retrospective
      Analysis.
AB  - In the development process for new drugs, dose-finding studies are of major
      importance. Absence of these studies may lead to failed phase 3 trials and
      delayed marketing authorization. In our study we investigated to what extent dose
      finding studies are performed in the case of orphan drugs for metabolic and
      oncologic indications. We identified all orphan drugs that were authorized until
      August 1, 2017. European Public Assessment Reports were used to extract the final
      dose used in the summary of product characteristics, involvement of healthy
      volunteers, study type, end points used, number of patients, number of doses,
      studies in special populations, and dose used for phase 3 studies. Each drug was
      checked for major objections and dose changes postmarketing. We included 49
      orphan drugs, of which 28 were indicated for metabolic disorders and 21 for
      oncologic indications. Dose-finding studies were performed in 32 orphan drugs,
      and studies in healthy volunteers in 26. The absence of dose-finding studies was
      mostly due to the rarity of the disease. In this case the dose was determined
      based on factors such as animal studies or clinical experience. Dose-related
      major objections were raised for 9 orphan drugs. Postmarketing dose-finding
      studies were conducted in 18 orphan drugs, but dose changes were applied in only
      2 drugs. In conclusion, dose-finding studies in the case of metabolic and
      oncologic orphan drugs were conducted in the development programs of two thirds
      of orphan drugs. Dose-finding studies performed postmarketing suggest that
      registered doses are not always optimal. It is thus important to perform more
      robust dose-finding studies both pre- and postmarketing.

PMID- 30192387
TI  - Evolution of parental activity at the nest is shaped by the risk of nest
      predation and ambient temperature across bird species.
AB  - Incubation is an important component of parental care in birds, and species
      differ widely in their incubation rhythm. In this comparative study, we focused
      on factors responsible for those differences. As hypothesized by A. Skutch,
      increased parental activity at the nest increases the probability of nest
      depredation. High risk of nest predation should therefore lead to the evolution
      of lower frequency of parental activity at the nest. We thus expected to find a
      negative relationship between frequency of nest visits and the risk of nest
      depredation. Using a large dataset of 256 species of passerines breeding
      worldwide, we found that the frequency of nest visits decreased as the risk of
      nest depredation increased and that this effect was strongest in tropical
      species. Further, foraging bouts were longer in species experiencing warmer
      ambient temperatures during incubation and those with domed nests. Incubation
      bouts were longer and frequency of nest visits was lower in species with higher
      body mass. Our results support the view that natural selection favors lower
      frequency of nests visits in species under higher risk of nest predation and
      demonstrate the importance of other factors (temperature, geographic space, nest
      type, and body mass) in shaping the evolution of incubation rhythm.

PMID- 30192389
TI  - Photodynamic inactivation of bacteria to decolonize meticillin-resistant
      Staphylococcus aureus from human skin.
AB  - BACKGROUND: To prevent infections that arise from the skin surface it is
      necessary to decolonize human skin prior to any proposed treatment or surgical
      intervention. Photodynamic inactivation of bacteria (PIB) uses cationic
      photosensitizers that attach to the surface of bacteria, generate reactive oxygen
      species on light irradiation and thereby kill bacteria via oxidative mechanisms.
      OBJECTIVES: To evaluate the potential and the safety of PIB for decolonization of
      bacteria from skin. METHODS: PIB with the new photosensitizer SAPYR [2-((4
      pyridinyl)methyl)-1H-phenalen-1-one chloride] was initially tested against
      different bacterial species in vitro. Then, ex vivo porcine skin samples were
      used as a model for decolonization of different bacteria species. The numbers of
      viable bacteria were quantified and the mitochondrial activity of skin cells was
      histologically analysed (using nitroblue tetrazolium chloride, NBTC). The same
      procedure was performed for human skin and meticillin-resistant Staphylococcus
      aureus (MRSA). RESULTS: The in vitro studies showed a 5 log10 reduction of all
      tested bacterial species. On ex vivo porcine skin samples, PIB reduced the
      viability of all tested bacterial species by at least 3 log10 steps. On human
      skin samples ex vivo, PIB reduced the number of viable MRSA by maximal 4.4 log10
      steps (1000 MUmol L-1 SAPYR, incubation time 10 min, 60 J cm-2 ). NBTC staining
      showed normal mitochondrial activity in skin cells after all PIB modalities.
      CONCLUSIONS: The results of this study show that PIB can effectively and safely
      kill bacteria like MRSA on the skin surface and might have the potential of skin
      decolonization in vivo.

PMID- 30192390
TI  - No Clinical Impact of CYP3A5 Gene Polymorphisms on the Pharmacokinetics and/or
      Efficacy of Maraviroc in Healthy Volunteers and HIV-1-Infected Subjects.
AB  - Maraviroc is a C-C chemokine receptor type-5 antagonist approved for the
      treatment of HIV-1. Previous studies show that cytochrome P450 3A5 (CYP3A5) plays
      a role in maraviroc metabolism. CYP3A5 is subject to a genetic polymorphism. The
      presence of 2 functional alleles (CYP3A5*1/*1) confers the extensive metabolism
      phenotype, which is rare in whites but common in blacks. The effect of CYP3A5
      genotype on maraviroc and/or metabolite pharmacokinetics was evaluated in 2
      clinical studies: a post hoc analysis from a phase 2b/3 study (NCT00098293)
      conducted in 494 HIV-1-infected subjects (study 1) in which the impact on
      maraviroc efficacy in 303 subjects was also assessed, and a study conducted in 47
      healthy volunteers (study 2). In study 2 (NCT02625207), extensive metabolizers
      had 26% to 37% lower mean area under the concentration-time curve compared with
      poor metabolizers (no CYP3A5*1 alleles). This effect diminished to 17% in the
      presence of potent CYP3A inhibition. The effect of CYP3A5 genotype was greatest
      in the formation of the metabolite (1S,2S)-2-hydroxymaraviroc. In study 1, the
      CYP3A5*1/*1 genotype unexpectedly had higher maraviroc area under the curve
      predictions (20%) compared with those with no CYP3A5*1 alleles. The reason for
      this disparity remains unclear. The proportions of subjects with viral loads <50
      and <400 copies/mL for maraviroc were comparable among all 3 CYP3A5 genotypes. In
      both studies maraviroc exposures were in the range of near-maximal viral
      inhibition in the majority of subjects. These results demonstrate that although
      CYP3A5 contributes to the metabolism of maraviroc, CYP3A5 genotype does not
      affect the clinical response to maraviroc in combination treatment of HIV-1
      infection at approved doses.

PMID- 30192391
TI  - Volume dependence in hypoxia-targeted dose escalation.
AB  - PURPOSE: Dose painting techniques based on dose escalation to hypoxic regions are
      usually governed by the spatial distribution of Oxygen Enhancement Ratio (OER)
      derived from PET or MRI images. The goal of this article is to show that the
      volume of the hypoxic region is also a parameter which may affect the
      radiobiological effectiveness of hypoxia-targeted dose escalation. METHODS: Our
      analysis is performed using the equation for Tumor Control Probability (TCP)
      derived from Poisson statistics. A tumor response model based on two levels of
      oxygenated and hypoxic cells with the survival curves described by the Linear
      Quadratic (LQ) model was used in the calculations. The model allows for
      analytical solutions which can be used for additional validation of our numerical
      simulations. The model was used to compute the average tumor cell survival that
      defines TCP. Dependence of average tumor cell survival on the relative hypoxic
      volume and dose escalation was computed for the conventional 30 * 2 Gy and
      hypofractionated 4 * 12 Gy dose regimens in a model problem with radiobiological
      parameters for nonsmall cell lung cancer. RESULTS: We show that equal average
      tumor cell survival and TCP can be achieved with smaller hypoxia-targeted dose
      escalation for smaller relative hypoxic volumes if the dose escalation does not
      exceed 50% of dose in the oxygenated region. This effect is explained by the
      dependence of average tumor cell survival and TCP mostly on the hypoxic tumor
      volume in this dose escalation range. Assuming a linear relationship between the
      number of clonogens and the hypoxic volume, smaller hypoxic volumes have smaller
      number of clonogens, therefore, smaller doses are needed to eradicate them.
      CONCLUSIONS: The theoretical analysis performed in this article predicts that
      tumors with smaller relative hypoxic volumes may require smaller hypoxia-targeted
      dose escalation to maintain equal TCP. The results of this research can be used
      for dose de-escalation strategies in dose painting techniques which may reduce
      dose to normal tissue and normal tissue complications without deterioration of
      TCP.

PMID- 30192388
TI  - Effects of lorazepam and baclofen on short- and long-latency afferent inhibition.
AB  - KEY POINTS: Short-latency afferent inhibition (SAI) is modulated by GABAA
      receptor activity, whereas the pharmacological origin of long-latency afferent
      inhibition remains unknown. This is the first study to report that long-latency
      afferent inhibition (LAI) is reduced by the GABAA positive allosteric modulator
      lorazepam, and that both SAI and LAI are not modulated by the GABAB agonist
      baclofen. These findings advance our understanding of the neural mechanisms
      underlying afferent inhibition. ABSTRACT: The afferent volley evoked by
      peripheral nerve stimulation has an inhibitory influence on transcranial magnetic
      stimulation induced motor evoked potentials. This phenomenon, known as afferent
      inhibition, occurs in two phases: short-latency afferent inhibition (SAI) and
      long-latency afferent inhibition (LAI). SAI exerts its inhibitory influence via
      cholinergic and GABAergic activity. The neurotransmitter receptors that mediate
      LAI remain unclear. The present study aimed to determine whether LAI is
      contributed by GABAA and/or GABAB receptor activity. In a double-blinded, placebo
      controlled study, 2.5 mg of lorazepam (GABAA agonist), 20 mg of baclofen (GABAB
      agonist) and placebo were administered to 14 males (mean age 22.7 +/- 1.9 years)
      in three separate sessions. SAI and LAI, evoked by stimulation of the median
      nerve and recorded from the first dorsal interosseous muscle, were quantified
      before and at the peak plasma concentration following drug ingestion. Results
      indicate that lorazepam reduced LAI by ~40% and, in support of previous work,
      reduced SAI by ~19%. However, neither SAI, nor LAI were altered by baclofen. In a
      follow-up double-blinded, placebo-controlled study, 10 returning participants
      received placebo or 40 mg of baclofen (double the dosage used in Experiment 1).
      The results obtained indicate that SAI and LAI were unchanged by baclofen. This
      is the first study to show that LAI is modulated by GABAA receptor activity,
      similar to SAI, and that afferent inhibition does not appear to be a GABAB
      mediated process.

PMID- 30192392
TI  - Rapid hepatitis C virus clearance by antivirals correlates with immune status of
      infected patients.
AB  - Altered immune parameters associated with hepatitis C virus (HCV) genotype 1b
      infection and their correlation with virus eradication in direct-acting
      antivirals (DAA)-treated patients were examined. Thirty-one HCV-infected patients
      were treated with DAAs for 12 weeks. Pre-DAA-treatment and post-DAA-treatment
      sera were analyzed for cytokines/chemokines using MILLIPLEX MAP. Serum complement
      level and antibody neutralization activity were measured separately. Sera from 11
      spontaneously cleared HCV subjects were included for comparison. Rapid
      virological responders (RVR) or end-of-treatment responders (EOTR) were defined
      as patients with HCV RNA negative at week 4 or positive at week 4 and negative at
      week 12, respectively. HCV RNA eradication and a decrease in liver fibrosis
      related cytokines after treatment were observed when compared with pretreatment
      sera from RVR and EOTR. In pretreatment sera, interferons and T-helper 1 or 2
      cell-associated cytokines/chemokines were significantly higher among RVR as
      compared with EOTR. Furthermore, serum complement and virus neutralizing antibody
      levels were higher in pretreatment RVR sera. Eradication of HCV RNA by DAA
      decreased liver fibrosis-related cytokines. Pretreatment sera from RVR displayed
      an enhanced cytokine/chemokine, complement and virus neutralizing antibody
      response as compared with EOTR sera. Our results suggested that enhanced host
      immune status may play an additive role on HCV RNA clearance by DAA.

PMID- 30192393
TI  - The nationwide distribution and trends of hepatitis C virus genotypes in mainland
      China.
AB  - Comprehensive data on hepatitis C virus (HCV) genotypes distribution is critical
      for treatment regimen selection, vaccine design, and drug development. This study
      aimed to understand the dynamic distribution of HCV genotypes in Mainland China.
      Three hundred sixty-two studies published from January 1993 to December 2017
      involving 64 891 samples (5133 injecting drug users, 2748 volunteer blood donors,
      1509 former paid plasma donors, 160 sexually encounters, and 1992 human
      immunodeficiency virus (HIV)/HCV coinfection patients) were eligible for the
      quantitative synthesis estimation. Pooled proportion of HCV genotypes (and 95%
      confidence intervals [CIs]) was estimated through the Freeman-Tukey double
      arcsine transformation by period, region, and risk group. A sharp decline of the
      subtype 1b was observed in all regions except in northwestern and central
      regions. The genotypes 3 and 6 showed an obvious increase in southern and
      southwestern regions and have already spread nationwide. After 2010, subtype 1b
      was the most dominant variant in all regions and risk groups, accounting for
      54.0% (95% CI, 51.9-56.1) of all national infections. Subtype 2a was the second
      most prevalent strain in all regions except in the south and southwest, with
      15.4% (95% CI, 13.1-17.8) national infections. The subtype 6a in southern region
      and 3b and 3a in southwestern region had a higher proportion of infections than
      that in other regions. In addition, the genotypes 3 and 6 are already prevalent
      in almost all risk groups. The distribution of HCV genotypes were sharply
      shifting in China in the past three decades. The HCV subtype 1b posed a sharp
      decline, whereas genotypes 3 and 6 played an increasing role in the regional and
      populational HCV pandemic.

PMID- 30192394
TI  - Dietary Macronutrient Composition Determines the Contribution of DGAT1 to
      Alcoholic Steatosis.
AB  - BACKGROUND: The first stage of alcoholic liver disease is hepatic steatosis.
      While alcohol is known to profoundly impact hepatic lipid metabolism, gaps in our
      knowledge remain regarding the mechanisms leading to alcohol-induced hepatic
      triglyceride (TG) accumulation. As the sole enzymes catalyzing the final step in
      TG synthesis, diacylglycerol O-acyltransferase (DGAT) 1 and 2 are potentially
      important contributors to alcoholic steatosis. Our goal was to study the effects
      of dietary fat content on alcohol-induced hepatic TG accumulation, and the
      relative contribution of DGAT1 and DGAT2 to alcoholic steatosis. METHODS: These
      studies were carried out in wild-type (WT) mice fed alcohol-containing high-fat
      or low-fat formulations of Lieber-DeCarli liquid diets, as well as follow-up
      studies in Dgat1-/- mice. RESULTS: A direct comparison of the low-fat and high
      fat liquid diet in WT mice revealed surprisingly similar levels of alcoholic
      steatosis, although there were underlying differences in the pattern of hepatic
      lipid accumulation and expression of genes involved in hepatic lipid metabolism.
      Follow-up studies in Dgat1-/- mice revealed that these animals are protected from
      alcoholic steatosis when consumed as part of a high-fat diet, but not a low-fat
      diet. CONCLUSIONS: Dietary macronutrient composition influences the relative
      contribution of DGAT1 and DGAT2 to alcoholic steatosis, such that in the context
      of alcohol and a high-fat diet, DGAT1 predominates.

PMID- 30192395
TI  - Oral immunization with recombinant Lactococcus lactis NZ9000 expressing human
      papillomavirus type 16 E7 antigen and evaluation of its immune effects in female
      C57BL/6 mice.
AB  - The ORFs of both native and codon-optimized E7 genes were successfully fused to
      SPusp45 signal peptide and expressed by a nisin-controlled gene expression system
      in the NZ9000 strains of Lactococcus lactis. Recombinant strains were confirmed
      by Western blot analysis. To measure immune responses against the E7 antigen,
      specific-pathogen-free C57BL/6 mice were inoculated with L lactis harboring
      pNZ8123-rE7 by oral gavage. Then, specific antibodies and cytokines were measured
      by enzyme-linked immunosorbent assay and enzyme-linked immunospot assay,
      respectively. Oral administration of L lactis strains expressing rE7 elicited the
      highest levels of E7-specific antibody and greatest numbers of E7-specific CD4+ T
      helper and CD8+ T cell precursors. Our outcomes indicated that the HPV-16 E7
      specific IL-2- and IFN-gamma-secreting T cells in antigen-stimulated splenocytes
      and intestinal mucosal lymphocytes were significantly higher than the control
      groups. Our data also demonstrated that mice vaccinated with recombinant L lactis
      were able to generate potent protective effects against challenge with the E7
      expressing tumor cell line (TC-1). Moreover, L lactis containing pNZ8123-HPV16
      optiE7 showed strong therapeutic antitumor effects against established tumors in
      vivo. These findings demonstrate that recombinant L lactis induce both humoral
      and cellular immune responses in mice and are therefore recommended for
      therapeutic treatments in humans after oral administration.

PMID- 30192396
TI  - Epidemiological trends and molecular dynamics of dengue, chikungunya virus
      infection, coinfection, and other undifferentiated fever during 2015-2016 in
      Odisha, India.
AB  - Chikungunya virus (CHIKV) infection is spatiotemporally related to dengue virus
      (DENV) infection and mostly undiagnosed due to similar primary symptoms. In 2013,
      a high rate (36%) of coinfection of DENV and CHIKV was reported in Odisha. Hence,
      the hospital-based study was continued to synthesis current epidemiological
      understanding of their single distribution or coinfection. Suspected DENV
      patients serum samples were tested for DENV and CHIKV by serology and reverse
      transcription polymerase chain reaction. The positive samples were used for
      analysis of mutation, selection pressure, and phylogenetic relationship. Clinical
      information was also analyzed. Among 648 (2015 and 2016) suspected DENV patients,
      141 (21.7%) were positive for DENV (serotypes 1-3), 22 (3.4%) were positive for
      CHIKV (ECSA) and 4 (2.8%) were coinfected with both. Sequence analysis showed
      four consistent mutations (M104V, V112A, K166N, and F169L) in CprM gene of DENV 2
      and two consistent mutations (M269V, D284E) in E1 gene of CHIKV. Interestingly,
      the CHIKV- E1 A226V mutation was absent in the studied population. It was also
      noticed that the peak incidence of both the infections occurs in August-September
      in 2015-16. Moreover, Plasmodium species, Salmonella typhi, and Rickettsial typhi
      infections were also observed in DENV patients. Different etiology was also
      detected in other undifferentiated fever patients as mixed infections (malaria,
      S. typhi, and R. typhi ). Hence, this investigation shows the significant
      reduction of DENV-CHIKV coinfection as compared with previous report, the burden
      of arboviruses and acute undifferentiated fever in Odisha in 2015-2016,
      highlighting the importance of epidemiological picture of febrile patients for
      appropriate patient management.

PMID- 30192397
TI  - Respiratory viral infections in infants with possible sepsis.
AB  - BACKGROUND: Knowledge of infections leading to sepsis is needed to develop
      comprehensive infection prevention and sepsis, as well as early recognition and
      treatment strategies.The aim of this study was to investigate the etiology of
      sepsis and evaluate the proportion of respiratory viral pathogens in infants
      under two years of age with possible sepsis. METHODS: The prospective study was
      performed in two years. Multiplex reverse transcriptase polymerase chain reaction
      (RT-PCR) was performed to detect viral pathogens. All patients who were included
      in this study had sepsis symptoms as defined by the Surviving Sepsis Campaign.
      RESULTS: We compared 90 patients with sepsis into three groups as patients (n =
      33) who had only viral positivity in nasopharyngeal swab, patients (17) had
      proven bacterial infection with or without viral infection, and patients (40)
      without the pathogen detection. Human rhinovirus (16.7%) and influenza (7.8%)
      were the most commonly seen viruses. A cough was more common in the viral
      infection group than other groups ( P = 0.02) and median thrombocyte count was
      lower in the bacterial infection group than the others ( P = 0.01). Patients
      having bacterial sepsis had the longest duration of hospitalization than the
      other groups ( P = 0.04). During winter and spring seaons, patients with sepsis
      had more viral infection; however, in summer and autumn period, patients were
      mostly in a state that we could not prove infection agents ( P = 0.02).
      CONCLUSIONS: Our results suggest that respiratory tract viruses may play an
      important role in patients with sepsis and they should be kept in mind,
      especially during winter and spring seasons. In overall infection, viral
      respiratory viruses as a single pathogen with a detection rate of 36.6% in sepsis
      etiology.

PMID- 30192398
TI  - Epidemiology of human astroviruses among children younger than 5 years:
      Prospective hospital-based sentinel surveillance in South Africa, 2009-2014.
AB  - BACKGROUND: The epidemiology of human astroviruses (HAstVs) in hospitalised
      patients less than 5 years of age from selected sites in South Africa was
      investigated. Diarrheagenic stool specimens collected from April 2009 to May 2014
      were screened retrospectively for selected viruses, bacteria and parasites.
      METHOD: Patient data were analysed to identify epidemiologic factors most
      frequently detected with HAstV infections. The following case-comparisons were
      investigated; HAstV-positive and HAstV-negative children, human immunodeficiency
      virus (HIV)-infected and HIV-uninfected (HAstV-positive) children and HIV-exposed
      and unexposed (HAstV-positive HIV-uninfected) children. RESULTS: Astrovirus was
      identified in 7.0% (234/3340) of cases and most frequently in ages 7 to 12 months
      (9.2%; 90/975) compared with 5.8% to 6.6% in other 6-month age groups. No
      seasonal trends were observed. More HAstVs were detected in children from homes
      that used outdoor water sources (7.6%) compared to indoor sources [5.7%; adjusted
      odds ratio (aOR), 1.5; 95% CI, 1.1-2.1; P = 0.009]. Astroviruses were detected in
      8.4% (67/799) of HIV-uninfected patients that were exposed to HIV compared with
      5.9% (74/1257) of HIV-unexposed patients ( P = 0.032). CONCLUSION: Astroviruses
      were most prevalent in children aged 7 to 12 months and were detected throughout
      the study period. The study was limited as only hospitalised patients were
      investigated and no comparisons were made to diarrhoea-free control groups.
      Future HAstV surveillance should include community-based studies and children
      presenting at outpatient facilities.

PMID- 30192400
TI  - Pyoderma gangrenosum triggered by switching from adalimumab to secukinumab.

PMID- 30192399
TI  - Efficiencies and kinetics of infection in different cell types/lines by African
      and Asian strains of Zika virus.
AB  - After recent outbreaks, Zika virus (ZIKV) was linked to severe neurological
      diseases including Guillain-Barre syndrome in adults and microcephaly in
      newborns. The severities of pathological manifestations have been associated with
      different ZIKV strains. To better understand the tropism of ZIKV, we infected 10
      human and four nonhuman cell lines (types) with two African (IbH30656 and MR766)
      and two Asian (PRVABC59 and H/FP/2013) ZIKV strains. Cell susceptibility to ZIKV
      infection was determined by examining viral titers, synthesis of viral proteins,
      and replication of positive and negative strands of viral genome. Among nonhuman
      cell lines, only Vero cells were efficiently infected by ZIKV. Among human cell
      lines, all were permissive to ZIKV infection. However, 293T and HeLa cells showed
      differential susceptibility towards African strains. In 293T cells, the NS1
      protein was expressed at the high level by African strains but was almost not
      expressed by Asian strains though there was no obvious difference in viral genome
      replication, suggesting that the differential susceptibility might be controlled
      at the stage of viral protein translation. This study provides comprehensive
      results of the permissiveness of different cell types to both African and Asian
      ZIKV strains, which might help clarify their different pathogenesis.

PMID- 30192401
TI  - Anticoagulation after successful atrial fibrillation ablation: Brushing your
      teeth may keep you off of blood thinners.

PMID- 30192402
TI  - Impact of air-handling system exhaust failure on dissemination pattern of
      simulant pathogen particles in a clinical biocontainment unit.
AB  - Biocontainment units (BCUs) are facilities used to care for patients with highly
      infectious diseases. However, there is limited guidance on BCU protocols and
      design. This study presents the first investigation of how HVAC (heating,
      ventilation, air-conditioning) operating conditions influence the dissemination
      of fluorescent tracer particles released in a BCU. Test conditions included
      normal HVAC operation and exhaust failure resulting in loss of negative pressure.
      A suspension of optical brightener powder and water was nebulized to produce
      fluorescent particles simulating droplet nuclei (0.5-5 MUm). Airborne particle
      number concentrations were monitored by Instantaneous Biological Analyzers and
      Collectors (FLIR Systems). During normal HVAC operation, fluorescent tracer
      particles were contained in the isolation room (average concentration = 1 * 104
      +/- 3 * 103 /Lair ). Under exhaust failure, the automated HVAC system maximizes
      airflow into areas adjacent to isolation rooms to attempt to maintain negative
      pressure differential. However, 6% of the fluorescent particles were transported
      through cracks around doors/door handles out of the isolation room via airflow
      alone and not by movement of personnel or doors. Overall, this study provides a
      systematic method for evaluating capabilities to contain aerosolized particles
      during various HVAC scenarios. Recommendations are provided to improve situation
      specific BCU safety.

PMID- 30192403
TI  - Further evidence for sustainable alternatives to replace threatened animal horn
      based on quantitative proteomic analysis.
AB  - In the present study, a quantitative proteomic approach was used to analyze and
      compare the proteome in horns from endangered species (rhinoceros, Saiga
      antelope, and Tibetan antelope) and common species (yak, water buffalo, and goat)
      based on the isobaric tag for relative and absolute quantification techniques. In
      total, 591 proteins were identified, and 321 were quantified and categorized
      based on molecular function, cellular component, and biological process.
      Principal component analysis and hierarchical clustering analysis results based
      on differences in the amount of protein identified three major clusters, and
      proteins including transglutaminase, desmocollin, and elongation factors were
      selected as trait components from proteomic patterns of horn samples from
      different species. Quantitative proteomic analysis based strategies can therefore
      provide further evidence for sustainable alternatives to replace animal horn from
      threatened species.

PMID- 30192404
TI  - miR-330-3p promotes lung cancer cells invasion, migration, and metastasis by
      directly targeting hSOD2b.
AB  - Lung cancer is a serious threat to human health. Studies have revealed that human
      manganese superoxide dismutase (hSOD2) and miRNAs play an essential role in the
      metastasis process of lung cancer. However, the miRNAs that associated with hSOD2
      and involved in metastasis, remain elusive. After databases analysis and dual
      luciferase reporter validation, we demonstrated that miR-330-3p expression
      inversely correlated with hSOD2b expression level, and that miR-330-3p directly
      targeted the 3'untranslated region (3'UTR) of hSOD2b. Furthermore, overexpression
      of miR-330-3p promoted whereas knockdown of miR-330-3p inhibited
      invasion/migration and the epithelial-mesenchymal transition (EMT) process of
      lung cancer cells in vitro. Knockdown of miR-330-3p inhibited metastasis of lung
      cancer cells in vivo. Moreover, miR-330-3p-mediated enhancement of
      invasion/migration in 95-D cells could be rescued by over-expression of hSOD2. In
      conclusion, we demonstrated that miR-330-3p promoted metastasis of lung cancer
      cells by suppressing hSOD2b expression and unveiled a new clinical application of
      miR-330-3p in the therapy of lung cancer.

PMID- 30192405
TI  - Corrective ventilation strategies in delivery room resuscitation of preterm
      infants.
AB  - AIM: Corrective ventilation strategies (CVS) during neonatal resuscitation and
      stabilisation (R&S) are taught through the MRSOPA mnemonic: Mask adjustment,
      Repositioning airway, Suctioning, Opening the mouth, Increasing inspiratory
      Pressure, and Alternative airway. The aim was to examine the use of CVS and to
      investigate the relationship between MRSOPA strategies and intubation of very
      preterm infants <32 weeks' gestation in the delivery room. METHODS: Retrospective
      review of video recordings of R&S of preterm infants born in Cork University
      Maternity Hospital, Ireland. RESULTS: In 46 resuscitation recordings, mask
      adjustment was observed in almost all (95.6%), followed by suctioning, (23.9%),
      opening the mouth (100%), increasing inspiratory pressure (81.0%) and intubation
      (32.6%). The most frequently used mask holds were: one-handed (95.6%), two-handed
      (63.0%), stem hold (23.8%), and modified spider hold (6.5%). There were no
      significant associations between individual mask holds and intubation. The more
      CVS employed the greater the need for intubation. CONCLUSION: The greater the
      number of MRSOPA strategies used in the delivery room, the more likely intubation
      occurred. Further studies may identify the effect of these CVS on short- and long
      term outcomes, in order to enhance R&S training and clinical practice.

PMID- 30192406
TI  - Detection of regulatory T cell phenotypic markers and cytokines in patients with
      human papillomavirus infection.
AB  - Infection with human papillomavirus (HPV) is the main cause of cervical cancer.
      Viral persistence is considered the main risk factor for neoplastic progression
      and evidence suggests that regulatory T cells (Treg) play an important role in
      the failure of viral elimination. The aim of this study was to detect phenotypic
      markers of Treg and cytokines interleukin (IL)-10 and transforming growth factor
      (TGF)-beta, in the cervical microenvironment of HPV-infected patients. One
      hundred and one samples of uterine cervix embedded in paraffin were analyzed. We
      used immunohistochemistry to examine the coexpression of the CD25/FOXP3 and
      CD4/TGF-beta markers, and the expression of GITR and IL-10 in cells present in
      the cervical stroma. We detected a microenvironment composed of high proportions
      of CD25+ FOXP3+ , CD4+ TGFbeta+ , IL-10+ , and GITR+ cells in samples with high
      viral loads and severe lesions of HPV-infected patients. The abundance of these
      markers, indicative of the presence of Treg cells and immunosuppressive
      cytokines, was significantly associated with severe lesions and elevated viral
      loads in the examined samples. These results suggest that Treg cells may be
      involved in maintaining a microenvironment favorable for viral persistence and
      neoplastic progression. Our findings support those of previous studies that
      suggested that these markers could be used to predict HPV persistence and
      neoplastic progression, and as potential targets for immune response modulation.

PMID- 30192407
TI  - The prenatal diagnosis of aortopulmonary window by fetal echocardiography.
AB  - OBJECTIVE: The purpose of this study was to analyze the fetal echocardiographic
      features and the associated anomalies of prenatal aortopulmonary window (APW).
      METHODS: We retrospectively reviewed the fetal echocardiographic database (n = 24
      000) in our hospital between May 2012 and December 2017. The general clinical
      information, fetal echocardiographic features, and the associated anomalies in
      patients with APW were analyzed. Four patients had undergone whole genome
      sequencing using fetal tissues. RESULTS: Six cases of APW confirmed by autopsy
      were identified in our fetal echocardiographic database. On the three-vessel
      view, a communication between the pulmonary artery trunk and ascending aorta was
      noted above the two semilunar valves in all cases. The most frequent type of APW
      among the cases was type II, and all cases were associated with other cardiac
      anomalies. No pathogenic or suspected pathogenic copy number variation or
      insertion-deletions were detected in this series. CONCLUSION: Prenatal diagnosis
      of APW is feasible, which is helpful during prenatal consultations, so that
      parents can make better decisions regarding postpartum treatment options and
      pregnancy outcomes.

PMID- 30192408
TI  - Evaluation of right atrial volumes and functions by real-time three-dimensional
      echocardiography in patients after acute inferior myocardial infarction.
AB  - BACKGROUND: Right ventricle (RV) involvement causes acute systolic and diastolic
      functional alterations in the RV in patients after inferior myocardial infarction
      (IMI), which may result in an increase in left ventricle (LV) end-diastolic and
      right atrial (RA) pressure. In our study, we sought to evaluate RA volumes and
      mechanical functions using real-time three-dimensional echocardiography (RT3DE)
      in IMI patients with or without RV involvement. METHODS: Ninety-six consecutive
      patients with IMI (mean age: 59.7 +/- 10.2 years, 60 female) were included. RV
      myocardial involvement (RVMI) was defined as the presence of a culprit lesion at
      the proximal portion of the first RV marginal branch in coronary angiography. The
      study population was divided into two groups: IMI (58.3%) and IMI + RVMI (41.7%).
      Patients were evaluated using conventional two-dimensional echocardiography (2DE)
      and RT3DE. RESULTS: In RT3DE measurements, IMI + RVMI patients had significantly
      higher RA phasic volumes and worse conduit mechanical function. A receiver
      operating characteristic (ROC) curve analysis revealed that an RT3DE RA maximum
      volume (Vmax) index > 27.9 mL/m2 was an independent predictor of RV involvement
      in patients after acute IMI, with a sensitivity of 80.0% and a specificity of
      89.3%. CONCLUSIONS: Right ventricle involvement may cause an increase in RA
      phasic volumes and deterioration of conduit function in patients with acute IMI.

PMID- 30192409
TI  - Patient, parent and professional perception of the use of maintenance enteral
      nutrition in Paediatric Crohn's Disease.
AB  - AIM: Maintenance enteral nutrition (MEN) is routinely used in Paediatric Crohn's
      Disease (CD) to prolong remission although there is limited evidence for efficacy
      and a lack of formal guidelines. This study surveyed patients', parents' and
      professional experience with MEN. METHODS: Two questionnaires were developed to
      survey the experience of MEN; (i) Patients/Parents (children >10 years of age
      aimed to complete independently) and (ii) Dietitians. Questionnaires were sent to
      families prescribed MEN after exclusive enteral nutrition (EEN) between 2015-17
      (n = 77) and dietitians working in paediatric regional centres in UK (n = 23).
      RESULTS: Response rate to the questionnaires was 53% patients, 62% parents and
      83% dietitians. Patients/parents reported medical/dietetic advice to be the
      primary factor affecting compliance, 30% patients reported side effects. Fifty
      six per cent of patients/58% parents stated a preference for dietary advice
      rather than MEN. Dietetic responses indicated 79% used MEN after EEN as standard
      procedure and 79% did not have exit criteria for MEN. Sixty-eight per cent
      perceived the taste was the primary factor affecting patient compliance.
      CONCLUSION: Patients' perception of the usefulness of MEN differs to
      professionals. This study highlights the extensive practice of MEN after EEN in
      clinical remission, which may not be nutritionally indicated. Patient preference
      is for dietary advice rather than MEN.

PMID- 30192410
TI  - Infant body mass index growth patterns predicted overweight at five years, waist
      to-height ratio did not add to this predictivity.
AB  - AIM: The aim of the present study was to examine body mass index (BMI) and waist
      to-height ratio (WHtR) growth patterns from birth until five years regarding
      their ability to predict overweight or obesity in children at five years of age.
      METHODS: Population-based longitudinal birth cohort study of 1540 children from
      the south-west region of Sweden, recruited at the first visit to the child health
      care centres in 2007-2008. The children were followed for five years and
      classified into two weight groups according to the 2012 International Obesity
      Task Force criteria. BMI and WHtR standard deviation scores (SDS) were analysed
      with Student's t-tests and multiple logistic regression models. RESULTS: BMI-SDS
      and WHtR-SDS growth patterns were from an early age different in children with
      overweight or obesity, compared to in children with normal weight or underweight.
      Overweight or obesity was significantly predicted by BMI-SDS at 0-1 month (p <
      0.001), DeltaBMI-SDS between 0-1 and 12 months (p < 0.001) and between 18 and 48
      months (p < 0.001), but not by WHtR-SDS, except for a negative association
      between 18 and 48 months in the boys (p = 0.040). CONCLUSION: Overweight or
      obesity at five years could be predicted by early BMI-SDS growth patterns, and
      WHtR-SDS did not add to the predictivity with regard to BMI-SDS.

PMID- 30192411
TI  - Determination of kinetic parameters of redox reactions using CE-ICP-MS: A case
      study for the reduction of Np(V) by hydroxylamine hydrochloride.
AB  - The rate constants k of the reduction of 5 * 10-5  M Np(V) to Np(IV) by
      hydroxylamine hydrochloride (HAHCl) in 1 M HCl have been determined by CE-ICP-MS
      in the temperature range of theta = 30-70 degrees C and with varying
      concentrations of HAHCl from 1 to 7.2 M. The reaction was found to have
      (pseudo)first order kinetics with respect to HAHCl. The experimental results for
      k ranged from 0.0029(1) min-1 (theta = 40 degrees C, c(HAHCl) = 3 M) to 0.039(7)
      min-1 (theta = 60 degrees C, c(HAHCl) = 7.2 M). The activation energy of the
      reaction was determined as EA  = (72 +/- 10) kJ/mol. These results and a
      comparison with literature data show that the coupling of CE to ICP-MS provides a
      powerful analytical tool for the investigation of the kinetic aspects of redox
      reactions of actinides at low concentrations. On the basis of this proof-of
      principle study, the method presented here can be extended to the investigation
      of the kinetic parameters of other redox systems containing different actinides
      (or transition metals) and oxidants/reductants.

PMID- 30192412
TI  - Retrospective time estimation following damage to the prefrontal cortex.
AB  - Time estimation in patients with prefrontal cortex (PFC) damage is often
      inaccurate. The relationship between PFC and estimation of short time intervals
      has been examined. However, it remains unclear whether PFC damage affects
      estimation of longer time intervals. Here, we investigated the ability of
      patients and healthy subjects to verbally estimate a period of 30 min, using a
      method easily applied in clinical settings. In 99 patients with brain damage, we
      compared under and normal ranges of time in patients with PFC damage or damage to
      other brain areas with the chi-squared test. Subsequently, we conducted a
      discriminant analysis and a multiple linear regression analysis to identify
      specific brain areas affecting time estimation. We observed a significantly
      larger number of patients who overestimated 30 min in the group with bilateral
      PFC damage compared to patients with damage to other regions. Discriminant
      analysis revealed that damage of right lateral PFC and left medial PFC
      contributed to discrimination between the normal range and overestimation groups.
      Multiple linear regression analysis indicated that right lateral PFC damage
      strongly affected overestimation of a 30-min interval. Neuropsychological test
      results revealed lower general cognitive function scores and orientation scores
      in overestimation group. The length of estimated time and the score of delayed
      word recall were negatively correlated. We propose that these may require
      encoding, maintenance, and updating of memory and are indirectly related to
      contextual memory. We discuss hypotheses on contextual memory segmentation and
      reconstruction to clarify the mechanism of impaired time overestimation in PFC
      damaged patients.

PMID- 30192413
TI  - Chemical space of Escherichia coli dihydrofolate reductase inhibitors: New
      approaches for discovering novel drugs for old bugs.
AB  - Escherichia coli Dihydrofolate reductase is an important enzyme that is essential
      for the survival of the Gram-negative microorganism. Inhibitors designed against
      this enzyme have demonstrated application as antibiotics. However, either because
      of poor bioavailability of the small-molecules resulting from their inability to
      cross the double membrane in Gram-negative bacteria or because the microorganism
      develops resistance to the antibiotics by mutating the DHFR target, discovery of
      new antibiotics against the enzyme is mandatory to overcome drug-resistance. This
      review summarizes the field of DHFR inhibition with special focus on recent
      efforts to effectively interface computational and experimental efforts to
      discover novel classes of inhibitors that target allosteric and active-sites in
      drug-resistant variants of EcDHFR.

PMID- 30192414
TI  - Palatability of Hypoallergenic Formulas for Cow's Milk Allergy and Healthcare
      Professional Recommendation.
AB  - BACKGROUND: Cows' milk protein allergy (CMPA) is the most common food allergy in
      infants in the United Kingdom. Infants with CMPA who are not exclusively
      breastfed require a substitute hypoallergenic formula, which are perceived as
      having a poor palatability. This study compares the palatability of different
      extensively hydrolysed formulas (EHFs) and explores healthcare professional (HCP)
      expectations of how palatability impacts infants and their families. METHODS:
      HCPs with experience of CMPA were recruited to take part in a home palatability
      test of four EHFs [Aptamil Pepti 1,Nutricia Ltd. (EHF W1), Althera, Nestle Health
      Science (EHF W2), Similac Alimentum, Abbott (EHF C1), Nutramigen LGG 1, Mead
      Johnson (EHF C2)] using a blind taste procedure. A randomised, complete block
      design was used to minimise order and carry-over biases. Participants completed a
      questionnaire about the impact of formula palatability on infants and their
      families. RESULTS: 100 HCPs took part (51 dietitians and 49 general
      practitioners). Overall whey-based lactose-containing EHFs were ranked the most
      palatable: EHF W1 by 77% of participants, EHF W2 by 20%. EHF W1 was liked
      significantly more (p < 0.0001) than the other formulas. The vast majority of
      participants agreed that better palatability would result in an increased chance
      of non-rejection (96%), more content families (92%) and decreased healthcare
      costs (90%). CONCLUSION: Amongst HCPs who manage infants with CMPA, whey-based
      lactose-containing EHFs were ranked the most palatable. HCPs expected that good
      palatability would result in better acceptance, more content infants and
      families, alongside decreased wastage and health care costs. This article is
      protected by copyright. All rights reserved.

PMID- 30192415
TI  - Minocycline decreases Th2 chemokines from M2 macrophages: Possible mechanisms for
      the suppression of bullous pemphigoid by traditional bullous disease drugs.
AB  - Minocycline/tetracycline is clinically used for the treatment of bullous
      pemphigoid (BP), and its clinical benefits are superior to those of prednisolone
      when considering adverse events. Although the clinical benefits of
      minocycline/tetracycline are well known, its immunosuppressive mechanisms are
      still unclear. In this study, we investigated the immunomodulatory effects of
      traditional anti-BP drugs (minocycline, nicotinic acid amide, dexamethasone and
      cyclosporine) on CD163+ M2 macrophages in vitro, with special focus on the
      production of CCL18 and CCL22, both of which are produced by CD163+ M2
      macrophages in the lesional skin of BP and are increased in the serum of BP
      patients. Minocycline decreased the production of CCL22, CCL24 and CCL26 as well
      as CCL2 from M2 macrophages. CCL18 from M2 macrophages was decreased by
      dexamethasone and cyclosporine, but not decreased by minocycline. These data
      suggest that the clinical benefit of minocycline is partially explained by its
      suppressive effects against the production of specific Th2 chemokines from M2
      macrophages, which should contribute to the recruitment of Th2 cells and
      eosinophils in the lesional skin of BP patients.

PMID- 30192417
TI  - Endoscopic purse-string suture technique: An effective remedy for a large
      iatrogenic rectal perforation.

PMID- 30192416
TI  - The association between ST18 gene polymorphism and severe pemphigus disease among
      Iranian population.
AB  - Recently, ST18 polymorphism has played a role in increasing the risk of pemphigus
      among some populations such as Egyptian and Jewish. In addition, a variant within
      the ST18 promoter gene was shown to induce ST18 upregulation and cytokine
      secretion leading to keratinocyte susceptibility to anti-desmoglein antibodies.
      Thus, the present study aimed to assess the ST18 single nucleotide polymorphisms
      (SNP) relationship with pemphigus, disease severity and family history among
      Iranian population. A total of 111 pemphigus patients and 201 healthy controls
      were genotyped for three ST18 SNPs rs2304365, rs10504140 and rs4074067 by using
      TETRA-ARMS PCR method. The results indicated that risk allele A in rs2304365 was
      significantly higher in pemphigus patients, compared with the amount in the
      control group (OR = 2.43 CI = 1.49-3.975, P < 0.001). Thus, A allele represents a
      risk factor for pemphigus. Further, the patients carrying the risk allele had a
      more severe disease and a higher age of disease onset while no relationship was
      observed between the number of relapses and positive family history of pemphigus
      with the risk allele. Finally, dominant model was regarded as the strongest
      inheritance model for the associated risk. The present study confirmed the
      relationship between ST18 gene with pemphigus disease, a more severe disease, and
      a higher age of disease onset.

PMID- 30192418
TI  - Genome-wide identification of genes directly regulated by ChvI and a consensus
      sequence for ChvI binding in Sinorhizobium meliloti.
AB  - ExoS/ChvI two-component signaling in the nitrogen-fixing alpha-proteobacterium
      Sinorhizobium meliloti is required for symbiosis and regulates exopolysaccharide
      production, motility, cell envelope integrity and nutrient utilization in free
      living bacteria. However, identification of many ExoS/ChvI direct transcriptional
      target genes has remained elusive. Here, we performed chromatin
      immunoprecipitation followed by microarray analysis (chIP-chip) to globally
      identify DNA regions bound by ChvI protein in S. meliloti. We then performed qRT
      PCR with chvI mutant strains to test ChvI-dependent expression of genes
      downstream of the ChvI-bound DNA regions. We identified 64 direct target genes of
      ChvI, including exoY, rem and chvI itself. We also identified ChvI direct target
      candidates, like exoR, that are likely controlled by additional regulators.
      Analysis of upstream sequences from the 64 ChvI direct target genes identified a
      15 bp-long consensus sequence. Using electrophoretic mobility shift assays and
      transcriptional fusions with exoY, SMb21440, SMc00084, SMc01580, chvI, and ropB1,
      we demonstrated this consensus sequence is important for ChvI binding to DNA and
      transcription of ChvI direct target genes. Thus, we have comprehensively
      identified ChvI regulon genes and a 'ChvI box' bound by ChvI. Many ChvI direct
      target genes may influence the cell envelope, consistent with the critical role
      of ExoS/ChvI in growth and microbe-host interactions.

PMID- 30192419
TI  - Investigation of serum amino acids involved in gallic acid detoxification of
      formaldehyde by liquid chromatography/tandem mass spectrometry and neutral loss
      scan.
AB  - RATIONALE: Gallic acid is one of the most common polyphenols in natural products
      and human diet. The consumption of gallic acid reduces the incidence of
      cardiovascular diseases, chronic metabolic disorders and cancers. Most previous
      publications focused on the antioxidative or prooxidative properties of gallic
      acid. In the present work, gallic acid as a trapping agent of blood formaldehyde
      was investigated by liquid chromatography/tandem mass spectrometry (LC/MS/MS) and
      neutral loss scan. METHODS: Serum samples incubated with gallic acid were
      subjected to LC/MS/MS analysis using an LTQ XL ion trap mass spectrometer. The
      adduct ions of gallic acid-formaldehyde-amino acids were explored by
      investigation of their fragmentation patterns and neutral loss scan experiments.
      RESULTS: A series of Mannich adducts (namely, gallic acid-formaldehyde-alanine,
      gallic acid-formaldehyde-proline, gallic acid-formaldehyde-leucine or gallic acid
      formaldehyde-isoleucine and gallic acid-formaldehyde-phenylalanine) were
      identified as metabolites by neutral loss scan experiments. CONCLUSIONS: This
      work demonstrated that serum amino acids are involved in gallic acid
      detoxification of formaldehyde. Because excessive formaldehyde in blood is
      implicated in a variety of disease pathologies, detoxification of formaldehyde,
      especially endogenous formaldehyde, may be another health beneficial effect of
      gallic acid. It also suggested that more attention should be paid to Mannich-type
      metabolites of polyphenol-formaldehyde-amino acids in research into the
      pharmacokinetics and bioavailability of polyphenols.

PMID- 30192420
TI  - Aortic Versus Dual Perfusion for Retrieval of the Liver After Brain Death: A
      National Registry Analysis.
AB  - There is lack of consensus in the literature regarding the comparative efficacy
      of in situ aortic-only compared with dual (aortic and portal venous) perfusion
      for retrieval and transplantation of the liver. Recipient outcomes from the
      Australia/New Zealand Liver Transplant Registry (2007-2016), including patient
      and graft survival and causes of graft loss, were stratified by perfusion route.
      Subgroup analyses were conducted for higher-risk donors. A total of 1382 liver
      transplantation recipients were analyzed (957 aortic-only; 425 dual perfusion).
      There were no significant differences in 5-year graft and patient survivals
      between the aortic-only and dual cohorts (80.1% versus 84.6% and 82.6% versus
      87.8%, respectively) or in the odds ratios of primary nonfunction, thrombotic
      graft loss, or graft loss secondary to biliary complications or acute rejection.
      When analyzing only higher-risk donors (n = 369), multivariate graft survival was
      significantly less in the aortic-only cohort (hazard ratio, 0.49; 95% confidence
      interval, 0.26-0.92). Overall, there was a trend toward improved outcomes when
      dual perfusion was used, which became significant when considering higher-risk
      donors alone. Inferences into the ideal perfusion technique in multiorgan
      procurement will require further investigation by way of a randomized controlled
      trial, and outcomes after the transplantation of other organs will also need to
      be considered.

PMID- 30192421
TI  - Plate Design for and Cherry Picking of Bacterial RNAi Clones for Systematic Error
      Detection in High-Throughput Caenorhabditis elegans RNAi Screens.
AB  - Automated or semi-automated high-throughput RNAi screens are highly prone to
      systematic errors because of multistep repetitive protocols and extensive use of
      automated instruments. A well-designed RNAi library can help detect and minimize
      systematic human and robotic errors. In this unit, we describe how to design an
      RNAi bacterial library for use in conjunction with the well-studied nematode
      Caenorhabditis elegans for automated phenotypic screens. We provide strategies to
      design and assemble RNAi libraries to reduce or eliminate systematic errors.
      These strategies serve as a good quality-control check and facilitate obtaining
      high-quality data from a genome-wide and sub-library RNAi screen. (c) 2018 by
      John Wiley & Sons, Inc.

PMID- 30192422
TI  - Alternative lengthening of telomeres, ATRX loss and H3-K27M mutations in
      histologically defined pilocytic astrocytoma with anaplasia.
AB  - Anaplasia may be identified in a subset of tumors with a presumed pilocytic
      astrocytoma (PA) component or piloid features, which may be associated with
      aggressive behavior, but the biologic basis of this change remains unclear. Fifty
      seven resections from 36 patients (23 M, 13 F, mean age 32 years, range 3-75)
      were included. A clinical diagnosis of NF1 was present in 8 (22%). Alternative
      lengthening of telomeres (ALT) was assessed by telomere-specific FISH and/or
      CISH. A combination of immunohistochemistry, DNA sequencing and FISH were used to
      study BRAF, ATRX, CDKN2A/p16, mutant IDH1 p.R132H and H3-K27M proteins. ALT was
      present in 25 (69%) cases and ATRX loss in 20 (57%), mostly in the expected
      association of ALT+/ATRX- (20/24, 83%) or ALT-/ATRX+ (11/11, 100%). BRAF
      duplication was present in 8 (of 26) (31%). H3-K27M was present in 5 of 32 (16%)
      cases, all with concurrent ATRX loss and ALT. ALT was also present in 9 (of 11)
      cases in the benign PA precursor, 7 of which also had ATRX loss in both the
      precursor and the anaplastic tumor. In a single pediatric case, ALT and ATRX loss
      developed in the anaplastic component only, and in another adult case, ALT was
      present in the PA-A component only, but ATRX was not tested. Features associated
      with worse prognosis included subtotal resection, adult vs. pediatric, presence
      of a PA precursor preceding a diagnosis of anaplasia, necrosis, presence of ALT
      and ATRX expression loss. ALT and ATRX loss, as well as alterations involving the
      MAPK pathway, are frequent in PA with anaplasia at the time of development of
      anaplasia or in their precursors. Additionally, a small subset of PA with
      anaplasia have H3-K27M mutations. These findings further support the concept that
      PA with anaplasia is a neoplasm with heterogeneous genetic features and
      alterations typical of both PA and diffuse gliomas.

PMID- 30192423
TI  - A new complimentary web-based tool for manual analysis of microcirculation
      videos: Validation of the Capillary Mapper against the current gold standard AVA
      3.2.
AB  - OBJECTIVE: The aim of the current study was to compare a newly developed web
      based freely accessible software program for manual analysis of the
      microcirculation, the Capillary Mapper (CM), with AVA 3.2 software (AVA;
      MicroVision Medical B.V., Amsterdam, The Netherlands), which is the current gold
      standard for analysis of microcirculation videos. METHODS: A web-based software
      program was developed, which enables manual analysis of videos of the
      microcirculation to be carried out according to recommendations of the 2018
      consensus conference. A set of 50 high quality microcirculation videos was
      analyzed with AVA and CM with respect to total vessel density, perfused vessel
      density, proportion of perfused vessels, and the microvascular flow index.
      RESULTS: Comparison of the mean values derived from manual analysis with CM and
      AVA revealed no significant differences in microcirculatory variables. Analysis
      according to Bland and Altman revealed an acceptable bias between manual analysis
      with the CM and AVA for all variables tested with sufficient limits of agreement.
      The analysis of intraclass correlation showed "excellent" agreement for all
      microcirculatory variables analyzed. CONCLUSIONS: The newly developed CM was
      successfully validated for manual analyses of microcirculation videos against the
      current gold standard, the software AVA 3.2.

PMID- 30192424
TI  - PE_PGRS3 of Mycobacterium tuberculosis is specifically expressed at low phosphate
      concentration, and its arginine-rich C-terminal domain mediates adhesion and
      persistence in host tissues when expressed in Mycobacterium smegmatis.
AB  - PE_PGRSs of Mycobacterium tuberculosis (Mtb) represent a family of complex and
      peculiar proteins whose role and function remain elusive. In this study, we
      investigated PE_PGRS3 and PE_PGRS4, two highly homologous PE_PGRSs encoded by two
      contiguous genes in the Mtb genome. Using a gene-reporter system in Mycobacterium
      smegmatis (Ms) and transcriptional analysis in Mtb, we show that PE_PGRS3, but
      not PE_PGRS4, is specifically expressed under low phosphate concentrations.
      Interestingly, PE_PGRS3, but not PE_PGRS4, has a unique, arginine-rich C-terminal
      domain of unknown function. Heterologous expression of PE_PGRS3 in Ms was used to
      demonstrate cellular localisation of the protein on the mycobacterial surface,
      where it significantly affects net surface charge. Moreover, expression of full
      length PE_PGRS3 enhanced adhesion of Ms to murine macrophages and human
      epithelial cells and improved bacterial persistence in spleen tissue following
      infection in mice. Expression of the PE_PGRS3 functional deletion mutant lacking
      the C-terminal domain in Ms did not enhance adhesion to host cells, showing a
      phenotype similar to the Ms parental strain. Interestingly, enhanced persistence
      of Ms expressing PE_PGRS3 did not correlate with increased concentrations of
      inflammatory cytokines. These results point to a critical role for the ~ 80 amino
      acids long, arginine-rich C-terminal domain of PE_PGRS3 in tuberculosis
      pathogenesis.

PMID- 30192426
TI  - Predation-mediated ecosystem services and disservices in agricultural landscapes.
AB  - Ecological intensification may reduce environmental externalities of agriculture
      by harnessing biodiversity to benefit regulating ecosystem services. However, to
      propose management options for the production of such services, there is a need
      to understand the spatiotemporal dynamics of net effects between ecosystem
      services and disservices provided by wild organisms across taxonomic groups in
      relation to habitat and landscape management. We studied the contribution of
      predatory vertebrates and invertebrates (including both carnivores and seed
      herbivores) to regulating ecosystem services and disservices in 16 cereal fields
      in response to a local habitat contrast and a landscape complexity gradient. From
      May to November 2016, we provided weed (predation reflects an ecosystem service)
      and crop (predation reflects a disservice) seeds, as well as pest (predation
      reflects an ecosystem service) and beneficial (predation reflects a disservice)
      invertebrate prey to predators. Seed predation was dominated by vertebrates,
      while vertebrates and invertebrates contributed equally to predation of animal
      prey. Before harvest, predation steadily increased from very low levels in May to
      high levels in July independent of the resource type. After harvest, ecosystem
      services declined more rapidly than disservices. The presence of adjacent
      seminatural grasslands promoted crop seed predation, but reduced pest prey
      predation. Predation on beneficial prey decreased with increasing proportions of
      seminatural grassland in the landscape. Predatory vertebrates and invertebrates
      provide important ecosystem services due to the consumption of pests. However,
      beneficial invertebrates and crop seeds were often consumed to a similar or even
      higher extent than harmful invertebrates or weed seeds. Our results therefore
      raise concerns that management options aimed at enhancing service providers may
      simultaneously increase levels of disservices. By considering positive and
      negative effects simultaneously, this study addresses an important knowledge gap
      and highlights the importance of interactions between local management, landscape
      composition, and service and disservice provision across taxa and over time.
      Considering trade-offs between ecosystem services and disservices when evaluating
      the net effects of biodiversity conservation measures on ecosystem service
      provision is crucial. Future agri-environment schemes that offer payments for
      seminatural habitats may need to provide higher compensation for farmers in cases
      where net effects are likely to be negative.

PMID- 30192425
TI  - Posttraumatic stress disorder and cigarette smoking: A systematic review.
AB  - BACKGROUND: Previous reviews of the PTSD and cigarette smoking literature showed
      high PTSD-smoking comorbidity and problematic smoking outcomes (Feldner et al.,
      2007, Clinical Psychology Review, 27, 14-45; Fu et al., 2007, Nicotine & Tobacco
      Research, 9, 1071-1084). However, past reviews also noted several prominent gaps
      in the literature, including a lack of etiological work examining underlying
      mechanisms and research on specialized PTSD-smoking treatments. The present
      review summarizes an extensive body of research conducted since the previous
      reviews targeting these areas of need. METHODS: Literature searches identified 66
      empirical studies specific to smoking and PTSD. RESULTS: Smokers were
      approximately twice more likely to have PTSD than nonsmokers in the general
      population, and individuals with PTSD were approximately twice as likely to be
      current smokers. Smokers with PTSD evidenced more negative affect, trauma
      history, and comorbid psychiatric history, as well as quit attempts and higher
      relapse rates. PTSD symptoms were associated with expectations that smoking would
      reduce negative affect, which, in turn, was associated with increased smoking
      rate and nicotine dependence. Male sex was associated with nicotine dependence
      and PTSD avoidance, while the relationship between PTSD and smoking relapse due
      to withdrawal was stronger in females. Specialized, integrated PTSD and smoking
      cessation treatments showed promise in increasing quit success relative to
      standard care in randomized trials. CONCLUSIONS: Rates of PTSD-smoking co
      occurrence remain high. Notable gains have been made in relevant epidemiological
      and etiological research, although more work is needed in trauma-specific
      subpopulations. Several promising specialized treatments for comorbid smoking
      PTSD have been developed and empirically tested but require replication.

PMID- 30192427
TI  - Catalytic isofunctional reactions - expanding the repertoire of shuttle and
      metathesis reactions.
AB  - Transfer hydrogenation, alkene metathesis and alkyne metathesis possess great
      value to the synthetic chemistry community. One of the key features of these
      processes is their reversibility which can be attributed to the presence of the
      same number and type of functional groups in both the reactants and products,
      making these reactions isofunctional. These classic reactions have recently
      inspired the development of novel shuttle and metathesis reactions that offer
      great promise for synthetic chemistry. This review describes and systematically
      categorizes both recent and older examples of shuttle and metathesis reactions
      other than transfer hydrogenation and alkene/alkyne metathesis.

PMID- 30192428
TI  - Voluntary Corn Oil Ingestion Increases Energy Expenditure and Interscapular UCP1
      Expression Through the Sympathetic Nerve in C57BL/6 Mice.
AB  - SCOPE: Previously, it has been found that corn oil ingestion activates both the
      gustatory system and brain reward system, stimulating motivation for eating. In
      the present study, the effect of voluntary corn oil ingestion on body weight gain
      and energy metabolism in mice is investigated. METHODS AND RESULTS: Voluntary
      corn oil ingestion with normal chow feeding does not lead to higher body weight
      than that of only the chow-fed control group. Mice that ingested corn oil have a
      higher total caloric intake and energy expenditure than did mice in the control
      group. Further, voluntary corn oil ingestion significantly upregulates Ucp1 mRNA
      and protein in interscapular brown adipose tissue (IBAT). Finally, the
      sympathetic nerve connected to IBAT was surgically transacted, then the body
      weight is measured for 8 weeks. IBAT sympathetic nerve transection surgery does
      not affect the body weight gain and food intake; however, when mice ingested corn
      oil, it induces significant body weight gain without changing the total caloric
      intake. IBAT sympathetic nerve transection surgery significantly suppresses UCP1
      upregulation by corn oil ingestion. CONCLUSION: The present data suggest that
      corn oil ingestion activates IBAT through the sympathetic nerve, upregulating
      UCP1 expression and increasing energy expenditure.

PMID- 30192429
TI  - Pharmacogenetics-based population pharmacokinetic analysis of gabapentin in
      patients with chronic pain: Effect of OCT2 and OCTN1 gene polymorphisms.
AB  - Gabapentin (GAB) is eliminated unchanged in urine, and organic cation
      transporters (OCT2 and OCTN1) have been shown to play a role in GAB renal
      excretion. This prospective clinical study aimed to evaluate the genetic
      polymorphisms effect on GAB pharmacokinetic (PK) variability using a population
      pharmacokinetic approach. Data were collected from 53 patients with chronic pain
      receiving multiple doses of GAB. Patients were genotyped for SLC22A2 c.808G>T and
      SLC22A4 c.1507C>T polymorphisms. Both polymorphisms' distribution followed the
      Hardy-Weinberg equilibrium. An one-compartment model with first-order absorption
      and linear elimination best described the data. The absorption rate constant,
      volume of distribution, and clearance estimated were 0.44 h-1 , 86 L, and 17.3 *
      (estimated glomerular filtration ratio/89.58)1.04  L/h, respectively. The genetic
      polymorphism SLC22A4 c.1507C>T did not have a significant influence on GAB
      absorption, distribution or elimination. Due to the low minor allelic frequency
      of SLC22A2 c.808G>T, further studies require higher number of participants to
      confirm its effect on GAB renal elimination. In conclusion, GAB clinical
      pharmacokinetics are strongly influenced by renal function and absorption
      process, but not by the OCTN1 (SLC22A4 c.1507C>T) polymorphism.

PMID- 30192430
TI  - Relationship between the endothelial glycocalyx and the extent of coronary
      atherosclerosis.
AB  - OBJECTIVE: To investigate the correlation between the EG and the severity of
      coronary atherosclerosis. METHODS: A total of193 subjects were divided into two
      groups. A SDF video microscope with a glycocalyx thickness measurement system was
      used to visualize the sublingual microcirculation. The levels of HA in the
      peripheral circulation and coronary circulation were determined via enzyme-linked
      immunosorbent assay. The number of coronary artery lesions and the Gensini score
      were used to evaluate the severity of the coronary atherosclerosis. RESULTS: EG
      thickness in the coronary heart disease (CHD) group (242.18 +/- 10.10 nm) was
      lower than that in the NON-CHD group (251.78 +/- 10.59 nm, P < 0.001). There was
      a negative correlation between the EG thickness and the number of coronary
      lesions and the Gensini score. The level of intracoronary HA in the CHD group
      (48.60, 126.27) was higher than that in the NON-CHD group (20.60, 34.45, P <
      0.001), and it was positively correlated with the number of coronary lesions and
      the Gensini score. CONCLUSIONS: EG damage was correlated with the occurrence and
      development of coronary atherosclerosis. The EG thickness in the capillaries of
      the oral submucosa and the intracoronary HA level can be used as auxiliary
      indexes to assess the severity of coronary atherosclerosis.

PMID- 30192432
TI  - Personal viewpoint on opioid agonist therapy and transplantation.
AB  - Opioid use disorder (OUD) is an increasing public health problem. Transplant
      centers worldwide are being confronted with increasing numbers of patients with
      opioid use disorder and end stage organ disease. Opioid agonist therapy (OAT; ie,
      methadone, buprenorphine, and buprenorphine/naloxone) is a scientifically proven,
      effective, physician-prescribed treatment for OUD. Although data in transplant
      populations remain limited, studies suggest that OAT does not appear to
      negatively affect graft or patient survival. Policies that require
      discontinuation of OAT for purposes of listing or transplantation contradict the
      evidence base for efficacy of OAT. Additional prospective outcomes studies on OAT
      and transplantation are needed. In the meantime, centers should not be asking
      patients to come off these effective treatments.

PMID- 30192431
TI  - Outcomes of treatment of faecal incontinence with sacral nerve stimulation - a
      Finnish multicentre study.
AB  - AIM: The aim of this multicentre study is to report the results of sacral nerve
      stimulation (SNS) treatment for faecal incontinence (FI) in Finland and determine
      factors that could influence SNS treatment outcomes. METHOD: This is a national
      multicentre study, involving all patients tested for SNS implantation in Finland
      from 1999 to 2017. Data were collected retrospectively from electronic patient
      archives and analysed for possible effects on treatment outcome. RESULTS: Of the
      432 patients with FI tested for SNS, 365 were women. Three hundred and thirteen
      (72.5%) of the tested patients advanced to permanent implantation of a
      stimulator. A successful final treatment outcome, with subjective alleviation of
      FI, was reported by 59.3% of the patients at the end of follow-up (mean 2.4
      years, range 8 days to 13.3 years). Patients with obstetric sphincter injury and
      idiopathic FI had more permanent stimulator implantations than patients with
      iatrogenic injury (P = 0.012). Male patients had significantly worse test phase
      outcomes than female patients (P < 0.001). Age did not influence treatment
      outcome (P = 0.446) CONCLUSION: Subjective final success of SNS treatment for FI
      was achieved in 59.3% of patients at a mean of 2.4 years. Gender and the
      aetiology of FI influenced the test phase and final treatment outcome of SNS
      treatment.

PMID- 30192433
TI  - Differential use of winter precipitation by upper and lower elevation Douglas fir
      in the Northern Rockies.
AB  - In temperate regions such as the American west, forest trees often exhibit growth
      sensitivity to climatic conditions of a particular season. For example, annual
      tree ring growth increments may correlate well with winter precipitation, but not
      with summer rainfall, suggesting that trees rely more on winter snow than summer
      rain. Because both the timing and character of seasonal western climate patterns
      are expected to change considerably over coming decades, variation in the
      importance of different seasonal moisture sources for trees can be expected to
      influence how different forest trees respond to climate change as a whole, with
      shifts in seasonality potentially benefitting some trees while challenging
      others. In this study, we inferred patterns of tree water use in Douglas fir
      trees from the Northern Rockies for 2 years using stable water isotopes, while
      simultaneously quantifying and tracking precipitation inputs to soil moisture
      across a vertical soil profile. We then coupled water source use with daily
      measurements of radial growth to demonstrate that soil moisture from winter
      precipitation accounted for 87.5% and 84% of tree growth at low and high
      elevations, respectively. We found that prevailing soil moisture conditions drive
      variation in the depth at which trees access soil water, which in turn determines
      which seasonal precipitation inputs are available to support tree growth and
      function. In general, trees at lower elevations relied more on winter
      precipitation sourced from deep soils while trees at higher elevations made
      better use of summer rains sourced from near-surface soil layers. As both the
      timing of seasons and phase of precipitation (rain vs. snow) are likely to change
      considerably across much of the west, such patterns in tree water use are likely
      to play a role in determining the evolution of forest composition and structure
      in a warming climate.

PMID- 30192434
TI  - Genotype-sensitive reversible and time-dependent CYP2D6 inhibition in human liver
      microsomes.
AB  - Cytochrome P450 (CYP) 2D6 metabolizes a wide range of xenobiotics and is
      characterized by a huge interindividual variability. A recent clinical study
      highlighted differential magnitude of CYP inhibition as a function of CYP2D6
      genotype. The aim of this study was to investigate the effect of CYP2D6 genotype
      on the inhibition of dextromethorphan O-demethylation by duloxetine and
      paroxetine in human liver microsomes (HLMs). The study focused on genotypes
      defined by the combination of two fully functional alleles (activity score 2, AS
      2, n = 6), of one fully functional and one reduced allele (activity score 1.5, AS
      1.5, n = 4) and of one fully functional and one non-functional allele (activity
      score 1, AS 1, n = 6), which all predict extensive metabolizer phenotype. Kinetic
      experiments showed that maximal reaction velocity was affected by CYP2D6
      genotype, with a decrease in 33% of Vmax in AS 1 HLMs compared to AS 2 (P =
      0.06). No difference in inhibition parameters Ki , KI and kinact was observed
      neither with the competitive inhibitor duloxetine nor with the time-dependent
      inhibitor paroxetine. Among the genotypes tested, we found no difference in
      absolute CYP2D6 microsomal levels with ELISA immunoquantification. Therefore, our
      results suggest that genotype-sensitive magnitude of drug-drug interactions
      recently observed in vivo is likely to be due to differential amounts of
      functional enzymes at the microsomal level rather than to a difference in
      inhibition potencies across genotypes, which motivates for further quantitative
      proteomic investigations of functional and variant CYP2D6 alleles.

PMID- 30192435
TI  - Program & Papers.

PMID- 30192437
TI  - Poster Session Abstracts.

PMID- 30192438
TI  - Symposium Summaries.

PMID- 30192439
TI  - Ectonucleotidase Inhibitory and Redox Activity of Imidazole-Based Organic Salts
      and Ionic Liquids.
AB  - Cytotoxicity against cancer and normal cells, inhibition of ectonucleotidase, and
      redox properties of a new group of imidazole-based organic salts and ionic
      liquids were studied. The tetrachloroferrate salt of a 1-methylimidazole
      derivative of salicylic aldehyde had most prominent inhibitory activity against
      ectonucleotidase as well as a higher cytotoxicity against HeLa cells and lower
      cytotoxicity against BHK-21 cells than the reference compound carboplatin. The
      studied compounds exhibited a moderate level of antioxidant activity with better
      results for the salicylic aldehyde derivatives than for spiropyrans. Moreover,
      these compounds did not generate singlet oxygen.

PMID- 30192440
TI  - Environmentally induced phenotypic plasticity explains hatching synchrony in the
      freshwater turtle Chrysemys picta.
AB  - Environmentally cued hatching allows embryos to alter the time of hatching in
      relation to environment through phenotypic plasticity. Spatially variable
      temperatures within shallow nests of many freshwater turtles cause asynchronous
      development of embryos within clutches, yet neonates still hatch synchronously
      either by hatching early or via metabolic compensation. Metabolic compensation
      and changes in circadian rhythms presumably enable embryos to adjust their
      developmental rates to catch up to more advanced embryos within the nest.
      Hatchlings of the North American freshwater turtle Chrysemys picta usually
      overwinter within the nest and emerge the following spring, but still hatch
      synchronously via hatching early. Here, we used rates of oxygen consumption and
      heart rate profiles to investigate the metabolic rates of clutches of C. picta
      developing in conditions that result in asynchronous development to determine if
      compensatory changes in metabolism occur during incubation. Embryos hatched
      synchronously and displayed circadian rhythms throughout incubation, but
      exhibited no evidence of metabolic compensation. Phenotypic traits of hatchlings,
      including body size and righting performance, were also not affected by
      asynchronous development. We conclude that less developed embryos of C. picta
      hatch synchronously with their clutch-mates by hatching early, which does not
      appear to inflict a fitness cost to individuals. The ultimate mechanism for
      synchronous hatching in C. picta could be for hatchlings to ensure an optimal
      overwintering position within the center of the nest. Consequently, immediate
      fitness costs will not hinder hatchling survival. The geographic location, as
      well as environmental and genetic factors unique to populations, can all
      influence hatching behavior in turtles through phenotypic plasticity. Hence,
      synchronous hatching is an adaptive bet-hedging strategy in turtles, but the
      mechanisms to achieve it are diverse.

PMID- 30192441
TI  - Pancreatic Beta Cell Differentiation From Human Pluripotent Stem Cells.
AB  - Insulin-expressing beta cells are crucial for the maintenance of systemic glucose
      homeostasis. Elucidation of the molecular and cellular mechanisms of beta cell
      development, expansion, survival, and function are required for full
      understanding of the molecular pathogenesis of diabetes. However, access to human
      beta cells for such studies is limited by virtue of the logistics of acquisition,
      prior medical status of donor, and imperfect culture systems for maintaining beta
      cell identity and function after isolation from human pancreas. Here, a technique
      for generation of beta cells from human pluripotent stem cells (hPSCs) by
      modification of key signaling pathways during islet development is described. Up
      to 70% C-peptide-positive beta cells can be obtained from endodermal anlagen
      after 27 days of differentiation with specific growth factors and small
      molecules. Although 50% of them are monohormonal C-peptide-positive cells and
      have molecular and cellular characteristics consistent with human beta cells in
      the Islets of Langerhans, a sub-population co-expressing other endocrine markers
      are also generated, indicating the immaturity of these cells. (c) 2018 by John
      Wiley & Sons, Inc.

PMID- 30192442
TI  - Schizophrenia in a Man With Probable Marfan Syndrome.

PMID- 30192443
TI  - QTc Prolongation in a Young Healthy Patient Receiving Citalopram 40 mg.

PMID- 30192445
TI  - Impact of Drug Adherence on Oppositional Defiant Disorder and Conduct Disorder
      Among Patients With Attention-Deficit/Hyperactivity Disorder.
AB  - OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) may be a predecessor
      of oppositional defiant disorder (ODD) and conduct disorder (CD), and medication
      is an effective treatment option for ADHD. This study aims to examine whether
      adherence to medication treatment is associated with developing ODD and CD among
      youths with ADHD. METHODS: A total of 33,835 youths (4 years <= age of diagnosis
      <= 18 years) with ADHD (ICD-9-CM code 314.X) undergoing medication treatment for
      at least 90 days were selected from Taiwan's National Health Insurance Research
      Database during the period of January 2000 through December 2009. Patients'
      medical records were monitored through December 31, 2011, or until they had a
      diagnosis of ODD or CD. We categorized participants as compliant or noncompliant
      on the basis of a medication possession ratio (MPR) of 50%. RESULTS: The patients
      with better drug adherence (MPR >= 50%) exhibited a significantly decreased
      probability of developing ODD (53% reduction, P < .001) or CD (58% reduction, P <
      .001) when compared to the patients with poor drug adherence (MPR < 50%). The
      results in our sensitivity analyses showed that good drug adherence consistently
      exerted protective effects on ODD or CD, irrespective of patients'
      characteristics. Moreover, the patients with the best drug adherence (MPR >= 75%)
      had the lowest risks of developing ODD or CD. CONCLUSION: Among patients with
      ADHD undergoing drug therapy, a better drug adherence is associated with a lower
      likelihood of their developing ODD or CD in later life.

PMID- 30192446
TI  - Cost-Effectiveness of Behavioral Activation for Depression in Older Adult
      Veterans: In-Person Care Versus Telehealth.
AB  - BACKGROUND: This study examined whether delivering behavioral activation for
      depression through telehealth is cost-effective compared to in-person care.
      METHODS: This was a randomized, noninferiority trial, with participants assigned
      to 1 of 2 arms of 8-week behavioral activation therapy: in-person or via
      telehealth. Primary clinical outcomes included measures of depression (Geriatric
      Depression Scale, Beck Depression Inventory, and Structured Clinical Interview
      for DSM-IV) at 12 months follow-up. Quality of life was assessed using the 36
      Item Short Form Health Survey. Economic outcomes included the difference in
      health services utilization costs between 1 year post-intervention and 1 year pre
      intervention, as quality-adjusted life-years (QALYs), and incremental cost
      effectiveness ratios for differences in cost based on mean travel and median
      travel relative to the 3 primary outcomes and QALYs. RESULTS: 241 participants
      were enrolled and completed study procedures between April 2007 and July 2012.
      Post-intervention, veterans treated in-person had a mean of $2,998 higher VA
      health care utilization costs relative to their pre-intervention utilization
      costs, while veterans treated via telehealth had a mean of $870.91 higher costs
      post-intervention relative to pre-intervention. The difference between bootstrap
      mean and median QALYs was not significantly different from zero. CONCLUSIONS:
      Although the intervention costs for telehealth were higher relative to in-person
      care, veterans receiving behavioral activation via telehealth had lower health
      utilization costs 1 year after the intervention than those receiving care in
      person while QALYs were approximately the same. These results demonstrate the
      noninferiority of telehealth in treating depression in veterans with respect to
      QALYs and a large and significant cost benefit of using telehealth in terms of
      health services utilization post-intervention. TRIAL REGISTRATION:
      ClinicalTrials.gov identifier: NCT00324701.

PMID- 30192444
TI  - Transdermal Nicotine for the Treatment of Mood and Cognitive Symptoms in
      Nonsmokers With Late-Life Depression.
AB  - OBJECTIVE: Late-life depression (LLD) is characterized by poor antidepressant
      response and cognitive dysfunction. This study examined whether transdermal
      nicotine benefits mood symptoms and cognitive performance in LLD. METHODS: In a
      12-week open-label outpatient study conducted between November 2016 and August
      2017, transdermal nicotine was given to 15 nonsmoking older adults (>= 60 years
      of age). Eligible participants met DSM-IV-TR criteria for major depressive
      disorder with >= 15 on the Montgomery-Asberg Depression Rating scale (MADRS) and
      endorsed subjective cognitive impairment. Transdermal nicotine patches were
      applied daily and titrated in a rigid dose escalation strategy to a maximum dose
      of 21.0 mg/d, allowing dose reductions for tolerability. The primary mood outcome
      was MADRS change measured every 3 weeks, with response defined as >= 50%
      improvement from baseline and remission as MADRS score <= 8. The primary
      cognitive outcome was the Conners Continuous Performance Test (CPT), a test of
      attention. RESULTS: Robust rates of response (86.7%; 13/15 subjects) and
      remission (53.3%; 8/15 subjects) were observed. There was a significant decrease
      in MADRS scores over the study (beta = -1.51, P < .001), with improvement seen as
      early as 3 weeks (Bonferroni-adjusted P value = .004). We also observed
      improvement in apathy and rumination. We did not observe improvement on the CPT
      but did observe improvement in subjective cognitive performance and signals of
      potential drug effects on secondary cognitive measures of working memory,
      episodic memory, and self-referential emotional processing. Overall, transdermal
      nicotine was well tolerated, although 6 participants could not reach the maximum
      targeted dose. CONCLUSIONS: Nicotine may be a promising therapy for depressed
      mood and cognitive performance in LLD. A definitive placebo-controlled trial and
      establishment of longer-term safety are necessary before clinical usage. TRIAL
      REGISTRATION: ClinicalTrials.gov identifier: NCT02816138.

PMID- 30192447
TI  - Suicidality 6 Years After Occupational Injury.
AB  - OBJECTIVE: Suicide attempts can result from traumatic events, including those
      caused by occupational injury. However, literature on the long-term prevalence
      rates of suicidality after occupational injury is relatively lacking. This study
      investigated the long-term prevalence of suicidality after occupational injury.
      METHODS: Between February 1 and August 31, 2009, 4,403 workers in Taiwan
      sustained occupational injuries and were hospitalized for 3 days or longer.
      Surveys were conducted at 3 and 12 months after occupational injury, and 2,308
      workers responded to either survey. They were invited to join the follow-up at 6
      years after occupational injury, using the Brief Symptom Rating Scale (BSRS-5),
      Posttraumatic Symptom Checklist (PTSC), and 1 question on suicidal ideation.
      Workers with a high score on the BSRS-5 or PTSC were invited to participate in an
      in-depth psychiatric evaluation using the Chinese version of the Mini
      International Neuropsychiatric Interview (MINI). RESULTS: The estimated MINI
      diagnosed suicidality rates at 3 months, 12 months, and 6 years after
      occupational injury were 5.4%, 4.8%, and 9.5%, respectively. Injured workers who
      reported that the injury majorly affected their physical appearance, experienced
      additional occupational injury requiring hospitalization for > 3 days, had
      unstable employment, and had lower income in the past 1 year than that before
      occupational injury had a higher risk of suicidal ideation. Injury majorly
      affecting the physical appearance, unstable employment, and lower income than
      that before occupational injury were the most crucial factors. These factors
      accounted for 12.7%, 13.2%, and 19.0% of suicidal ideation among the injured
      workers. CONCLUSIONS: The suicidality rate increased at 6 years after
      occupational injury. The relevant factors for suicidal ideation were injury
      severity and work instability. Periodic monitoring of psychological and physical
      health and economic stability are warranted.

PMID- 30192448
TI  - Depression Plays a Moderating Role in the Cognitive Decline Associated With
      Changes of Brain White Matter Hyperintensities.
AB  - OBJECTIVE: In the elderly, depression and white matter hyperintensities (WMH) are
      common and associated with cognitive impairment. This study investigated the
      possible interactions between depression and WMH in their influences on cognition
      of the elderly. METHODS: Using multiple neuropsychological tests, we evaluated
      the cognitive function of 122 community-dwelling elders with depression at
      baseline between November 2008 and February 2009. Major depressive disorder,
      dysthymic disorder, and minor depressive disorder were diagnosed according to DSM
      IV criteria. Subsyndromal depressive disorder was operationally defined using a
      modification of DSM-IV criteria. We visually rated WMH severity according to the
      modified Fazekas scale and calculated WMH volume using an automated method. We
      defined WMH (+) as having a score of 2 or higher on the modified Fazekas scale.
      In the 3-year follow-up study, baseline participants were reassessed between
      November 2011 and February 2013 with the same methodology. RESULTS: Baseline
      depression was associated with a decline over 3 years in the Categorical Verbal
      Fluency Test (VFT) (P = .001), Word List Memory Test (WLMT) (P = .019), Trail
      Making Test A (TMT-A) (P = .018), and Mini-Mental State Examination (MMSE) (P =
      .017), while baseline WMH (+) was associated with a decline in WLMT (P = .039)
      only. An increase of WMH volume over 3 years was associated with a decline in the
      performances of VFT (P = .044), WLMT (P = .044), Word List Recall Test (P =
      .040), Word List Recognition Test (P = .036), and TMT-A (P = .001) over the same
      period only in the subjects with depression at baseline. CONCLUSIONS: Depressive
      disorder and WMH are interactively associated with the poor performance of
      multiple cognitive functions. Depressive disorder may moderate the cognitive
      decline associated with the changes of brain WMH.

PMID- 30192449
TI  - Maternal Anxiety During Pregnancy and the Association With Adverse Perinatal
      Outcomes: Systematic Review and Meta-Analysis.
AB  - OBJECTIVE: This systematic review and meta-analysis examined the association
      between maternal antenatal anxiety (AA) and a range of perinatal outcomes. DATA
      SOURCES: Ovid MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations,
      PsycINFO, CINAHL, Embase, and the Cochrane Library were searched to May 31, 2016,
      using controlled vocabulary and keywords (eg, prenatal, anxiety, preterm). STUDY
      SELECTION: Perinatal outcomes of women with and without AA (diagnosed or self
      reported using validated scale) derived from English language, prospectively
      collected data were included. 1,458 abstracts were reviewed, 306 articles were
      retrieved, and 29 articles were included. DATA EXTRACTION: Two independent
      reviewers extracted data and assessed quality. Random-effects models were
      utilized for outcomes (>= 3 studies). Subanalyses examined potential effect
      moderators including study quality and diagnostic versus self-reported anxiety
      among others. RESULTS: Antenatal anxiety was associated with increased odds for
      preterm birth (pooled odds ratio [OR] = 1.54; 95% confidence interval [CI], 1.39
      to 1.70, 16 studies) and spontaneous preterm birth (OR = 1.41; 95% CI, 1.13 to
      1.75), lower mean birth weight (mean difference = -55.96 g; 95% CI, -93.62 to 
      18.31 g), increased odds for low birth weight (OR = 1.80; 95% CI, 1.48 to 2.18),
      earlier gestational age (mean difference = -0.13 wk; 95% CI, -0.22 to -0.04 wk),
      increased odds for being small for gestational age (OR = 1.48; 95% CI, 1.26 to
      1.74), and smaller head circumference (mean difference = -0.25 cm; 95% CI, -0.45
      to -0.06 cm). Heterogeneity between studies was not significant for most
      outcomes. Subanalyses for birth weight found women with diagnosed anxiety had
      infants with significantly lower birth weight (P < .03) compared to those
      identified with rating scales (although both subanalyses were significant [P <
      .01]). Associations between anxiety and preeclampsia, cesarean delivery, and
      Apgar scores were nonsignificant. CONCLUSIONS: Antenatal anxiety is associated
      with multiple adverse perinatal outcomes and is not benign. The impact of
      treating anxiety on these associations is unknown.

PMID- 30192450
TI  - Differences in Duloxetine Dosing Strategies in Smoking and Nonsmoking Patients:
      Therapeutic Drug Monitoring Uncovers the Impact on Drug Metabolism.
AB  - BACKGROUND: For certain psychotropic drugs, such as clozapine or olanzapine, the
      influence of smoking on drug metabolism is well studied. Tobacco smoke increases
      the metabolism of drugs that are substrates for cytochrome P450 (CYP) 1A2 due to
      CYP induction. The antidepressant duloxetine, acting as a serotonin
      norepinephrine reuptake inhibitor, is mainly metabolized via CYP1A2. To date,
      little is known about the influence of smoking on serum duloxetine
      concentrations. METHODS: A therapeutic drug monitoring database consisting of
      plasma concentrations of duloxetine collected from January 2013 to June 2017 was
      analyzed. A group of nonsmoking patients undergoing treatment with duloxetine (n
      = 89) was compared to a group of active smokers also receiving duloxetine (n =
      36). Serum concentrations of duloxetine and dose-adjusted serum concentrations
      were compared using non-parametric tests. RESULTS: Groups did not differ
      concerning sex (P = .063), but the group of active smokers was younger (P < .001)
      and received higher daily doses of duloxetine (P = .001). Smokers showed
      significantly lower median serum duloxetine concentrations (38.4% lower, P =
      .002) and 53.6% lower dose-adjusted serum concentrations (0.325 [ng/mL]/[mg/d] in
      smokers vs 0.7 [ng/mL]/[mg/d] in nonsmokers, P < .001). CONCLUSIONS: Despite
      higher daily doses, smokers had considerably lower serum duloxetine
      concentrations. The induction of CYP1A2 by tobacco smoke is a clinically relevant
      factor for drugs that are substrates for CYP1A2. Clinicians should actively
      assess smoking status, inform patients about the effect of smoking on duloxetine
      metabolism, and anticipate higher serum concentrations in the case of smoking
      cessation. Therapeutic drug monitoring ensures treatment efficacy by enabling the
      personalizing of treatment, as smokers need higher duloxetine doses to target
      serum concentrations within the therapeutic reference range.

PMID- 30192451
TI  - Suturing map for endoscopic mitral valve repair developed on high-fidelity
      endoscopic simulator.
AB  - Minimally invasive mitral valve surgery demands a different mind-set from
      surgeons due to its high complexity and steep learning curve, especially in a
      fully endoscopic approach. Smaller incisions, working with long-shafted
      instruments, and a relatively fixed camera position in a limited working space
      necessitate the development of new surgical routines.  We used a high-fidelity
      mitral valve simulator to develop a suturing map for placement of the
      annuloplasty ring with minimal tissue manipulation and maximal visual exposure.
      The suturing map could be helpful for less experienced surgeons who are starting
      to learn the techniques of minimally invasive mitral valve surgery.

PMID- 30192452
TI  - Thoracoscopic thymectomy using a left-side approach.
AB  - The surgical treatment of myasthenia gravis involves the complete resection of
      the thymus and the mediastinal fat between the two phrenic nerves. This procedure
      has been shown to have a positive impact on the rate of remission. In this video
      tutorial we illustrate the technical aspects of radical thymectomy using a left
      thoracoscopic approach.

PMID- 30192453
TI  - Transapical valve-in-ring mitral valve implantation through the anterior mitral
      valve leaflet.
AB  - Transcatheter mitral valve implantation (TMVI) is a relatively novel intervention
      used to replace the mitral valve of individuals deemed too high risk or
      unsuitable for surgery. It is associated with a number of specific risks,
      including left ventricular outflow tract obstruction (LVOTO).  In this video
      tutorial we present the case of a 75-year-old man who was unable to undergo redo
      surgical repair and had a number of risk factors for LVOTO. To minimize these
      risks, we deployed the TMVI within the anterior mitral valve leaflet. The
      postoperative result was mild mitral valve regurgitation and no LVOTO.  The long
      term outcome of this approach is yet to be determined but we believe this
      technique offers a novel method to manage a select group of patients suffering
      with mitral valve disease and at risk of LVOTO.

PMID- 30192454
TI  - [THE ROLE OF CORTICAL AND HIPPOCAMPAL GABAERGIC INTERNEURONS IN EPILEPSY].
AB  - The role of various classes of cortical and hippocampal interneurons in the
      pathogenesis of the temporal lobe epilepsy, which is among the most common forms
      of epilepsy, is discussed in this paper. The results of the morphological studies
      in postmortem brain tissue and electrophysiological experiments on brain slices
      of patients taken in neurosurgical operations as well as the results of in vivo
      and in vitro studies in animal models are critically reviewed. The selective
      elimination of the specific groups of interneurons and the functional disorders
      of the surviving interneurons causes the dysfunction of inhibitory processes in
      epileptic brain. The understanding of the specific role of different classes of
      interneurons in epileptic brain is a basis for the development of new effective
      treatment strategies.

PMID- 30192455
TI  - [Recent Progress at Atomic Spectrum Field for DBD Research and Development].
AB  - Because of its small volume, simple structure, low energy consumption, low
      working temperature, strong ability of sample dissociation/excitation and other
      significant characteristics, the dielectric barrier discharge is especially
      suitable for the miniaturization and portable analytical instruments. By now,
      atomizer or excitation source based on dielectric barrier discharge has applied
      in atomic absorption spectrometer, atomic fluorescence spectrometer and atomic
      emission spectrometer successfully, which promoted the development of
      miniaturization atomic spectrum instrument. This paper reviews DBD's recent
      progress in atomic spectrum field, emphatically introduces the applications of
      the DBD-AFS system in different sampling modes and analyses, along with their
      respective merits and demerits. This paper also introduces the new applications
      of DBD in vapor generation and direct solid sampling. Due to the DBD's reaction
      mechanism is still unclear; the study of its subsequent development may be
      restricted.

PMID- 30192456
TI  - [Preparation of Au Nanoparticles with Different Morphologies and Study of Their
      Property as Surface Enhanced Raman Scattering Substrates].
AB  - Different shapes of gold nanoparticles (NPs) have different enhancement effect in
      Surface Enhanced Raman Scattering (SERS). The polyhedral Au NPs have multiple
      angular structures, which show stronger enhancement effect than Au nanoplatelets.
      In recent years, the research on synthesis and properties of polyhedral Au NPs
      has attracted much attention. In this study the enhancement effect of the Au NPs
      in SERS was observed in Au NPs with the shape of dodecahedron, icosahedron,
      triangular plate and spherosome. Triangular Au NP films were prepared through a
      chemical reduction method using sodium borohydride as the reductant. As for
      synthesizing icosahedral Au NPs, Poly (vinyl pyrrolidone) is used as a capping
      agent and diethylene glycol is used as a reducing agent. Dodecahedral Au NPs were
      synthesized using icosahedral Au NPs as seeds. SERS spectra were detected for
      these three Au NPs as well as the traditional colloidal Au by using 4
      mercaptopyridine and 4-mercaptobenzoic as probing molecules. Triangular Au NP
      films, icosahedral Au NPs and dodecahedral Au NPs were with average diameters of
      about 130, 100 and 120 nm. UV/Vis spectroscopy indicated that these three Au NPs
      had typical absorbance bands at 589, 598 and 544 nm. The results show that the Au
      polyhedron has better enhancement ability than the Triangular NPs.

PMID- 30192457
TI  - [Fluorescence Anisotropy and Applications Based on Functional Nucleic Acid
      Recognition].
AB  - Based on the difference of the depolarization of the emitted light before and
      after the interaction of molecules, fluorescence anisotropy, also known as
      fluorescence polarization, can be beneficial for the study of interactions and
      the detection of the targets. In 1950s, Gregorio Weber first studied the
      interactions between dansyl chloride and bovine serum albumin or ovalbumin with
      fluorescence anisotropy method, which paved the way for fluorescence anisotropy
      in biochemical applications. Since the early 1990s, functional nucleic acids
      (FNAs, including aptamers, and nucleic acid enzymes) were discovered and
      synthesized, which have been widely used in functional nucleic acid-based
      sensing. Aptamers are oligonucleotides that can recognize and bind specifically
      to various molecular targets. The fluorescence anisotropy methods which are based
      on aptamer recognition have the advantages of high selectivity, sensitivity and
      through-put. They play an important role in the study of interaction with
      protein, nucleic acids and small molecules. However, the way of enhancing the
      fluorescence anisotropy change of small molecules associated with the binding
      events is challenging. This paper reviews the basic principles and designs of
      fluorescence anisotropy methods bases on functional nucleic acid recognition for
      study and detection of proteins, nucleic acids and small molecules that play an
      important role in the life activity.

PMID- 30192458
TI  - [Progress in the Analysis and Conservation of Cultural Relics and Artworks with
      Fiber Optic Reflectance Spectroscopy].
AB  - Cultural relics are non-renewable precious heritages, while artworks are limited
      cultural fortune. Therefore, it cannot afford any damage when cultural relics and
      artworks are analyzed. Fiber optic reflectance spectroscopy (FORS) has features
      of non-destructive testing, direct measurement and remote analysis and has its
      unique advantages in the research of cultural relics and artworks. This paper
      introduced the application of FORS in the identification pigments and dyes, the
      analysis of binders and the research of conservation results and preservation
      environments. Detection limits, reproducibility and signal characterization
      method were discussed. The future development of FORS in the research of cultural
      relics and artworks was summarized.

PMID- 30192459
TI  - [INTERACTION OF GLUTAMATE AND GABA RECEPTORS IN THE CENTRAL NERVOUS SYSTEM].
AB  - The article provides an overview of postsynaptic interaction of GABA and
      glutamate receptors in central neurons. Co-localization of GABA and glutamate in
      synapses, structure and function of their receptors and interaction of both
      ionotropic and metabotropic glutamate and GABA receptors are being discussed.

PMID- 30192460
TI  - [LONG-TERM EFFECTS OF STRESSFUL IMPACTS DURING NEONATAL PERIOD OF DEVELOPMENT ON
      NOCICEPTIVE SYSTEM AND PSYCHOEMOTIONAL BEHAVIOR].
AB  - Long-term effects of peripheral pain, brief stress of maternal isolation and
      their combination in one-day- and repeatedly two-day-old rat pups or seven-day-
      and repeatedly eight-day-old pups were investigated on indices of basal pain (in
      the absence of inflammation), a prolonged response to again evoked inflammation
      in the formalin test, the level of anxiety and depression and of spatial learning
      ability in the animals as adults (90-day-olds). Changes in the indices under
      investigation were revealed in adult rats depending on the type of early life
      impact and age during which it occurred: inflammatory pain induced hypoalgesia in
      the test of hot plate and deterioration in spatial learning ability in the Morris
      test; the stress of maternal isolation on the first and second days, but not
      seventh and eighth days of life caused a strengthening of formalin-induced pain
      response. Regardless of the age when rat pups were exposed to impact, again
      induced inflammation evoked strengthening of pain response when the animals
      reached adulthood. In the forced swim test the time of immobility was increased
      in rats exposed early to any from impacts investigated. The effect of combination
      pain with stress did not exceed the effect of each impact separately. The new
      data contribute to the urgent problem of the long-term effects of the damaging
      impacts of pain and stress during the neonatal period on the functional activity
      of the tonic nociceptive system and behavior.

PMID- 30192461
TI  - [Study on Pressure Characteristics of Photoacoustic Spectroscopy and TDLAS].
AB  - Based on priciples of PAS and TDLAS, relevance between them was dicussed, while
      the relationships of PAS and TDLAS signal with pressure were derived. A contrast
      device for making PAS and TDLAS gas detection simultaneously was designed and
      constructed to test different pressure and provide a reference for the gas
      measurement technology selection under different pressure conditions.
      Experimental studies show that: as the pressure rises, PAS and TDLAS signals
      become larger, and limit detection sensitivity are improved; with the rising
      pressure, conversion efficiency from energy absorbed by gas to PAS signals
      becomes low; at low pressure condiction, PAS is a better choice.

PMID- 30192462
TI  - [Synthesis and Fluorescence Properties of Rare Earth Ions Co-Doped CaMoO(4)].
AB  - In this paper, a series of CaMoO4 phosphor co-doped rare earth ions were prepared
      with chemistry co-precipitation method. The concentration of Pr(3+)/Tb(3+) and
      temperature had obvious influence on the luminescent properties. The crystal
      structures and spectrum characteristics of the samples were identified with X-ray
      powder diffraction (XRD) and fluorescence spectrophotometer (PL). According to
      XRD analysis, the main diffraction peaks of samples are consistent with the
      standard card (JCPDS 29-0351) of the diffraction peak data. This showed doped
      rare earth ions did not change matrix lattice structure. The emission spectrum
      excited by 275 nm exhibit sharp lines peaking at 488, 560, 621 and 560 nm
      assigned to the (3)P(0)-(3)H(4), (3)P(0)-(3)H(5),(1)D(2)-(3)H(4) and (3)P(0)
      (3)F(2) transitions of the Pr(3+) ions. The intensity of fluorescence reached the
      strongest when the concentration of the doping amount was 3%. The optimum
      calcination temperatures of CaMoO(4)?0.03Pr(3+) and CaMoO(4)?0.05Tb(3+) were 800
      and 600 C. Furthermore, the intensity of excitation spectra and emission spectra
      are dependent on the concentration of the doping amount. The emission spectra
      intensities of CaMoO(4)?Pr(3+) phosphors decrease and CaMoO(4)?Tb(3+) phosphors
      firstly increase and then decrease because of concentration quenching effect with
      increasing Pr(3+) and Tb(3+) concentration. In addition, the luminescence
      properties of Pr(3+) ion in CaMoO(4)?0.03Pr(3+), yTb(3+) system could be
      evidently improved with co-doping of Tb(3+) ions which was due to the efficient
      energy transfer process from Tb(3+) to Pr(3+) ions.

PMID- 30192463
TI  - Expanding Enrollment Without the Individual Mandate: Options to Bring More People
      into the Individual Market.
AB  - Issue: Recent changes to the Affordable Care Act, including elimination of the
      individual mandate penalty, the halting of federal payments for cost-sharing
      reductions, and expanded access to short-term plans, may reduce enrollment in the
      individual market. Goal: Analyze options to increase enrollment, accounting for
      recent policy changes. Methods: RAND's COMPARE microsimulation model is used to
      analyze six policies that would expand access to tax credits, increase their
      generosity, and fund a reinsurance program. Key Findings and Conclusions: The
      options would increase individual market enrollment by 400,000 to 3.2 million in
      2020. Net increases in total enrollment (300,000 to 2.4 million) are smaller
      because of offsetting decreases in employer-sponsored insurance. The largest
      gains are possible through two options: large-scale investment in reinsurance,
      and extension of tax credits to higher-income people combined with increases in
      the generosity of existing tax credits. If funded through a fee on health plans,
      reinsurance could be implemented without increasing the federal deficit.
      Additional taxpayer costs would increase by $1 billion to $23 billion, depending
      on the policy. While enhanced tax credits for young adults would lead to small
      coverage gains, they would entail the lowest costs to taxpayers among the six
      options.

PMID- 30192464
TI  - [Effect of Junction Temperature on EL Spectra of GaN-Based White High Voltage
      LEDs].
AB  - High voltage light emitting diodes (HV-LEDs) have potential advantages on general
      lighting application for their special features. But as novel power LEDs, their
      optical, electrical and thermal characteristics still need to be further studied.
      In this paper, 6 and 9 V GaN-based HV-LEDs were packaged in the same package
      structure and process conditions. The optical characteristics of two samples were
      investigated under different temperatures range from 10 to 70 C which were
      calibrated to junction temperatures using thermal impedance measurement. To
      ensure the same current density, working current was set to 150 mA for 6 V sample
      and 100 mA for 9 V sample respectively. Results show that the increasing junction
      temperature has a great effect on EL spectra of two samples, such as peak
      wavelength red-shifting, full width at half maximum (FWHM) broadening, luminous
      efficiency reducing and color rendering index (CRI) increasing. The junction
      temperature of 9V sample is lower than that of 6 V sample in the same platform
      temperature and injection power. With temperature increasing, the extended
      quantitative value of FWHM for 9 V sample is 1.3 nm less than that of 6 V sample,
      the reduced quantitative value of luminous efficiency is 1.13 lm.W(-1) less than
      that of 6 V sample, while the increased quantitative value of CRI is 0.28 less
      than that of 6 V sample. Those data suggest that EL spectra of HV-LEDs is less
      affected by junction temperature than traditional LEDs. It is because HV-LEDs
      perform better in current spreading and generate less heat. This conclusion has
      reference value for study, development and applications of GaN-based HV-LEDs. In
      addition, peak wavelength still has a good linear relationship with junction
      temperature and it can be a temperature-sensitive parameter when the spectra
      measurement accuracy is enough.

PMID- 30192465
TI  - [Spectral Matching Algorithm Applied to Identify the Terahertz Spectrum of Caulis
      Spatholobi and Caulis Sargentodoxae].
AB  - Caulis spatholobi and caulis sargentodoxae are two different kinds of traditional
      Chinese medicine, which are similar to each other in appearance, but they are
      from differ sources with different functions.. This paper presents their spectrum
      using terahertz time-domain spectroscopy technology combines spectral matching
      algorithm to identify five different kinds of these samples. Due to the complex
      chemical composition of traditional Chinese medicine, different components of the
      characteristic absorption peak occurred easily mutually overlapping, therefore,
      it's very difficult to find obvious characteristic absorption peak in terahertz
      range, caulis spatholobi and caulis like this. Every sample was measured 10 times
      in some position. These standard spectral data have been calculated in different
      frequency, data show good stability in range of 0.2~1.3 THz. The second order
      differential method is used to process the THz spectrum data from 0.2~1.3 THz.
      These tiny differences of absorption coefficient have been hemerged between
      caulis sargentodoxae and caulis spatholobi and compare with these data using the
      method of correlation coefficient block coding method, spectral angle method and
      information divergence method, respectively. The analysis results, the spectral
      angle method is the best algorithm, the discriminate accuracy of a total of 100
      sets of data is 95%. It is a new way to distinguish difference of traditional
      Chinese medicine.

PMID- 30192466
TI  - [THE PERMEABILITY OF DURA MATER OF SPINAL CORD CANINE FOR LOW-MOLECULAR AGENTS OF
      BLOOD SERUM].
AB  - We studied dura mater (DM) permeability of spinal cord canine in vitro for the
      low-molecular components of blood serum - urea, creatinine, glucose, lactate,
      cholesterol, calcium, and inorganic phosphate. We evaluated DM permeability for
      high-molecular compound of blood serum - albumin as a comparison marker. As
      established, most of the studied components had the permeability within 8-15 %.
      Maximum DM permeability was found for lactate (33.6 %), minimum one - for
      cholesterol (1.3 %). The permeability for urea and for creatinine was 8.0 and 7.5
      %, respectively; and herewith the permeability non-linear dependence on the
      initial substrate concentration in blood serum was observed. DM threshold
      permeability for urea was 4.83 mmol/L, for creatinine - 97 MUmol/L. The
      functional characteristics of DM permeability can be determined by its structural
      features - close packing of fibrillar structures connective tissue, high content
      of sulfated glycosaminoglycans, and the absence of non-sulfated ones.

PMID- 30192467
TI  - [Quality Optimization Method for Ambient CO(2) Inversion of High Resolution
      Fourier Transform Infrared Spectrum].
AB  - CO(2) retrievals with high quality facilitate resolving the sources and sinks of
      CO(2) are helpful in predicting the trend in climate change and understanding the
      global carbon cycle. Based on a nonlinear least squares spectral fitting
      algorithm, we investigate the optimization method for CO2 products derived from
      ground-based high resolution Fourier transform infrared spectra. The CO(2)
      vertical column densities (VCDs) are converted into column-averaged dry air mole
      fraction XCO(2) by using the fitted O(2) VCDs, and thus the system errors (e. g.
      pointing errors, ILS errors, zero-level offset) are corrected greatly. The
      virtual daily variation which is related to air mass factor is corrected with an
      empirical model. The spectra screening rule proposed in this paper can greatly
      improve the XCO2 quality. The CO(2) retrievals before and after the optimized
      method are compared using a typical CO(2) daily time series. After using the
      optimized method, the fitting error is reduced by 60%, and the two-hours-averaged
      precision is ~0.071% (equals to ~0.28 ppm), which is perfectly in line with the
      TCCON (the total carbon column observing network) threshold, i. e., less than
      0.1%.

PMID- 30192468
TI  - Incidental Bequests and the Choice to Self-Insure Late-Life Risks.
AB  - Despite facing significant uncertainty about their lifespans and health care
      costs, most retirees do not buy annuities or long-term care insurance. In this
      paper, I find that retirees' saving and insurance choices are highly inconsistent
      with standard life-cycle models in which people care only about their own
      consumption but match well models in which bequests are luxury goods. Bequest
      motives tend to reduce the value of insurance by reducing the opportunity cost of
      precautionary saving. The results suggest that bequest motives significantly
      increase saving and significantly decrease purchases of long-term care insurance
      and annuities.

PMID- 30192469
TI  - [The Research Development of FTIR in Analyzing Material Structures].
AB  - Safety issues of animal derived food have been emerging one after another, and
      the using of the illegal addictives and abuse of high-risk chemicals bred for
      livestock have been increasingly serious from melamine, lean meat powder, Sudan
      Red, plasticizing agent, waste oils to leather milk. How to determine these
      chemicals faces severe challenges. Infrared spectroscopy is the same powerful for
      material structures as nuclear magnetic resonance spectroscopy, mass spectrometry
      and ultraviolet spectrum. There are few researches about quality and safety of
      livestocks products. In this article, some researches in analyzing structures has
      been reviewed, including studies of spectral features, molecular conformation,
      stability, homologous series, derivative and reaction products, inferring
      functional groups of macromolecular compounds and molecular structural formula
      and distinguishing complex biological samples. Forming the new thought screening
      contaminants maybe used for animals is expected to early warning addictives
      causing serious food safety problems that is to build the comprehensive analysis
      methods for these matters on the basis of creating spectrum or functional groups
      databases designed for animal products.

PMID- 30192470
TI  - [PARAMETERS OF CEREBRAL CORTEX CAPILLARY NETWORK IN SHR RATS DURING THE
      DEVELOPMENT OF ARTERIAL HYPERTENSION AND STABLE HIGH BLOOD PRESSURE].
AB  - The studies were performed in hypertensive rats (SHR strain) during the period of
      hypertension development (7-8 weeks) and stable high blood pressure (16-17 weeks)
      and in normotensive rats (WKY strain) of corresponding ages. The average number
      of capillaries per square millimeter, the average capillaries diameter, and the
      capillary network structure following the estimation of capillaries distribution
      based on capillaries diameter within the following ranges (up to 3, from 3 to 5,
      from 5 to 7 and from 7 to 9 MUm) were investigated using the morphological
      approach. The average diameter of capillaries and capillary network structure in
      SHRs during the development of hypertension did not differ from the respective
      values in WKY rats of the same age. SHR rats showed disturbed
      microvascularisation by structural and functional rarefaction in the stable high
      blood pressure period, which was manifested in lower average capillaries density
      and average capillaries diameter as well as in substantial (2.5 times) increase
      in plasmatic capillaries as compared to WKY rats of the same age.

PMID- 30192472
TI  - [METABOLIC ACTIVITY OF LUNG AT EXPERIMENTAL BRAIN ISCHEMIA IN CONDITION OF
      CAPSAICIN BLOCKADE OF VAGUS NERVE].
AB  - In rats with ligation of both common carotid arteries in condition of bilateral
      capsaicin blockade of vagus nerve the metabolic functions of the lungs associated
      with their participation in the regulation of hemostasis, lipid composition of
      blood plasma and lung surfactant were investigated. It is shown that cerebral
      ischemia is accompanied by changes in the fractional composition of phospholipids
      in both arterial and venous blood, as well as in pulmonary surfactant, and the
      decrease of the lung hypocoagulation effect. The phagocytic activity of alveolar
      macrophages (as one of the factors involved in surfactant lipids metabolism) in
      brain ischemia is reduced. After the blockade of capsaicin-sensitive vagal
      afferents the changes in surfactant and plasma phospholipids caused by cerebral
      ischemia, are abolished, hypocoagulation effect of lung restores, but the
      functional activity of macrophages remains decreased. These findings suggest that
      capsaicin-sensitive vagal afferents are involved in the development of
      disregulatory disorders of lung metabolic function in cerebral ischemia.

PMID- 30192471
TI  - Medical Devices and Device-Led Combination Products; Voluntary Malfunction
      Summary Reporting Program for Manufacturers. Notification; order
      grantingalternative.
AB  - The Food and Drug Administration's (FDA, Agency, or we) Center for Devices and
      Radiological Health and Center for Biologics Evaluation and Research are
      announcing that the Agency is granting an alternative that permits manufacturer
      reporting of certain device malfunction medical device reports (MDRs) in summary
      form on a quarterly basis. We refer to this alternative as the "Voluntary
      Malfunction Summary Reporting Program." This voluntary program reflects goals for
      streamlining malfunction reporting outlined in the commitment letter agreed to by
      FDA and industry and submitted to Congress, as referenced in the Medical Device
      User Fee Amendments of 2017 (MDUFA IV Commitment Letter).

PMID- 30192473
TI  - [SEASONAL DIFFERENCES IN THE EFFECT OF MELATONIN ON THE MORPHO-FUNCTIONAL STATE
      OF THE THYROID GLAND SPONTANEOUSLY HYPERTENSIVE RATS].
AB  - We studied the effect of exogenous melatonin on the indicators of thyroid gland
      condition of the young spontaneously hypertensive rats in spring and autumn.
      These data suggested that after 28-day of melatonin administration (5 mg/kg) in
      different seasons of the year there were divergent effects on the state of the
      thyroid gland. So, melatonin increased synthetic activity of the gland in the
      spring. It was indicated by a reduction in the area of the follicular colloid,
      the inner diameter of the follicles, the number of connective tissue elements,
      increasing the height of thyrocytes, follicular colloidal index and reduced index
      accumulation colloid. Spontaneously hypertensive rats were less sensitive to the
      effects of melatonin in autumn. A significant increase in the number of the
      connective tissue elements, reduction of the follicular epithelium area and
      follicular colloidal index showed a decline in the functional activity of the
      thyroid gland after of melatonin administration in the autumn.

PMID- 30192474
TI  - [EFFECTS OF LIGHT OR DARK DEPRIVATION ON PERFORMANCE AND LACTATE LEVELS IN RAT
      BLOOD].
AB  - The dynamics of rat's swimming test with a load after 10 daily deprivation of
      light or dark were investigated. It was established that in the control group in
      nature illumination daily physical swimming with a load to full exhaustion from
      the first to the third day of the experiment, there was an increase of active
      swimming time indicator followed by stabilization. In groups of animals kept
      before bringing swimming test in a day and night lighting or darkening around the
      clock, there was an increase in swimming time only on the first day of the
      experiment, and the next days there was a decrease of efficiency. After a five
      day cycle of the swimming load the level of lactate in the blood of control
      animals was increased, and experienced - has not changed in comparison with the
      intact, not subjected to any stress.

PMID- 30192475
TI  - Medicare Program; Hospital Inpatient Prospective Payment Systems for Acute Care
      Hospitals and the Long-Term Care Hospital Prospective Payment System and Policy
      Changes and Fiscal Year 2019 Rates; Quality Reporting Requirements for Specific
      Providers; Medicare and Medicaid Electronic Health Record (EHR) Incentive
      Programs (Promoting Interoperability Programs) Requirements for Eligible
      Hospitals, Critical Access Hospitals, and Eligible Professionals; Medicare Cost
      Reporting Requirements; and Physician Certification and Recertification of
      Claims. Final rule.
AB  - We are revising the Medicare hospital inpatient prospective payment systems
      (IPPS) for operating and capital-related costs of acute care hospitals to
      implement changes arising from our continuing experience with these systems for
      FY 2019. Some of these changes implement certain statutory provisions contained
      in the 21st Century Cures Act and the Bipartisan Budget Act of 2018, and other
      legislation. We also are making changes relating to Medicare graduate medical
      education (GME) affiliation agreements for new urban teaching hospitals. In
      addition, we are providing the market basket update that will apply to the rate
      of-increase limits for certain hospitals excluded from the IPPS that are paid on
      a reasonable cost basis, subject to these limits for FY 2019. We are updating the
      payment policies and the annual payment rates for the Medicare prospective
      payment system (PPS) for inpatient hospital services provided by long-term care
      hospitals (LTCHs) for FY 2019. In addition, we are establishing new requirements
      or revising existing requirements for quality reporting by specific Medicare
      providers (acute care hospitals, PPS-exempt cancer hospitals, and LTCHs). We also
      are establishing new requirements or revising existing requirements for eligible
      professionals (EPs), eligible hospitals, and critical access hospitals (CAHs)
      participating in the Medicare and Medicaid Electronic Health Record (EHR)
      Incentive Programs (now referred to as the Promoting Interoperability Programs).
      In addition, we are finalizing modifications to the requirements that apply to
      States operating Medicaid Promoting Interoperability Programs. We are updating
      policies for the Hospital Value-Based Purchasing (VBP) Program, the Hospital
      Readmissions Reduction Program, and the Hospital-Acquired Condition (HAC)
      Reduction Program. We also are making changes relating to the required supporting
      documentation for an acceptable Medicare cost report submission and the
      supporting information for physician certification and recertification of claims.

PMID- 30192476
TI  - [NOTHROMBEL EFFECT ON THE EXPRESSION OF MEMBRANE COMPLEX GPIb-IX-V PLATELETS
      ACTIVATED BY THROMBIN].
AB  - The influence of Nothrombel on the expression of membrane complex GPIb-IX-V of
      platelets activated by thrombin was studied. It is established that Nothrombel
      reduced thrombin-induced expression of complex GPIb-IX-V on the membrane of the
      activated platelets. The inhibitory activity of Nothrombel on the expression of
      GPIb (CD42b) was comparable to its activity with respect to GPIX (CD42a) and is
      equal to 43 %. With regard to GPV (CD42d) inhibitory effect of the drug was less
      pronounced and is equal to 22 %. The possible targets for Nothrombel are
      activation of thromboxane signaling pathway, as well as GPIb-IX-V receptors of
      platelets itself.

PMID- 30192477
TI  - [BINDING OF CELL-DERIVED MICROPARTICLES WITH FIBRIN IN BLOOD CLOTTING].
AB  - Direct effects of circulating blood microparticles on fibrin formation and
      structure were studied. Clots made from platelet-free plasma and from
      microparticle-depleted plasma obtained by filtration was studied in parallel,
      including clots from the microparticle-depleted plasma replenished with
      phospholipids. Fibrin formation was induced by exogenous thrombin without Ca2+ to
      prevent formation of endogenous thrombin and exclude indirect kinetic effects of
      microparticles related to thrombin generation. In the presence of natural
      microparticles or exogenous phospholipids the maximal turbidity of fibrin clots
      was significantly smaller, indicating structural distinctions from the clots
      formed in the absence of microparticles. Scanning electron microscopy and
      confocal microscopy showed that clots formed from platelet-free plasma, i. e. in
      the presence of microparticles, unlike clots from the microparticle-depleted
      plasma, contained 0.1-0.5-MUm-large CD61-positive granules associated with fibrin
      fibers that were identical to the particles found on the surface of filters used
      for microparticle removal. The results show that platelet-derived microparticles
      bind to fibrin and affect its structure. The revealed interactions of cell
      derived microparticles with fibrin highlight a previously unknown role of
      microparticles in hemostasis and thrombosis as constituents and modulators of a
      fibrin clot structure.

PMID- 30192478
TI  - [HEART RATE VARIABILITY CHANGES DEMONSTRATED BY INDIVIDUALS WITH DIFFERENT
      VEGETATIVE REGULATION TYPES IN ORIGIN UNDER RERESPIRATION SESSION].
AB  - The studied in the paper is how breathing in isolated space (rerespiration)
      influences heart rate variability, arterial pressure indices, and composition of
      the expired gas in individuals with different vegetative regulation types in
      origin. Found that, the values and vector of the changes in low frequency indices
      of the power of heart rate spectrum before and within the process of
      rerespiration have been highly informative when assessing the leading type of
      vegetative regulation. The structure of intersystem correlations in the examined
      male subjects has specific features either at rest (baseline) or at breathing
      test that testifies to different mechanisms of maintaining functional abilities
      in sympathicotonic and vagotonic individuals undergoing hypoxic-hypercapnic gas
      mixture breathing.

PMID- 30192479
TI  - [INDIVIDUAL FEATURES VIEWING EMOTIONALLY MEANINGFUL IMAGES].
AB  - The data on the individual features of eye movements during viewing affective
      images from IAPS have been presented. The results suggest that the nature of the
      viewing of the trajectories for each subject (n = 20) is saved at a presentation
      of images with different emotional content. All examinees showed a significant
      correlation between the number of tests in which detected a region of interest,
      in three combinations: between negative and positive images, negative and
      neutral, neutral and positive (r = 0.84; 0.78 and 0.77 respectively). A similar
      correlation was found for the fixation duration (r = 0.90; 0.82; 0.90). It is
      shown that the number of points of fixation in the areas of interest, the area of
      the field viewing and the fixation duration significantly different between the
      two groups examinees (with a predominance of focal or scanning inspection
      trajectories). The possibility of using emotionally meaningful images to evaluate
      the dominate type of visual attention on the parameters of eye movements of a
      particular person is discussed.

PMID- 30192480
TI  - [Application of FTIR and Active Ingredients Quantitative Analysis on Quality
      Control of Dai Medicine Alstonia scholaris (L.) R. Br.].
AB  - FTIR fingerprint of the leaves and immature stems of Alstonia scholaris (L.) R.
      Br. was established as a content determination method for the detection of
      picrinine, ursolic acid and oleanolic acid. Different medicinal parts were
      identified based on principal component analysis, while exploring the influence
      of immature stems for the leaves and the application of FTIR and HPLC in the Dai
      quality control in order to speed up the pace of Dai medicine modernization.
      Infrared spectroscopy of different batches samples were collected and the data
      was preprocessed as to automatic baseline correction, smooth, ordinate
      normalization, second order derivative, and then to PCA, all the datum in
      triplicate. For content determination of picrinine, mobile phase was acetonitrile
      (40) water (contain 0.1% ammonia water) (60) and the wavelength was set at 287
      nm. For ursolic acid and oleanolic acid, the mobile phase was mixture (12?88) of
      0.1% formic acid in water (A) and methanol (B). Wavelength was 210 nm. As the
      results, the original spectrum difference was not obvious for leaves and stems.
      Pretreatment spectroscopy had a significant variation on absorption peak number
      and intensity in 3 000~2 800 and 1 800~500 cm(-1). The results of PCA showed
      that, the leaves and stems were separated; in addition the difference of
      different batches leaves was bigger than the stems. The mean contents of
      picrinine, ursolic acid and oleanolic acid in leaves were 0.79,8.47,7.51 and
      0.21,1.78,1.67 mg.g(-1) in stems, respectively. The content of ursolic acid and
      oleanolic acid is higher than picrinine, but ursolic acid and oleanolic acid
      content had no obvious difference. Mean content of three ingredients in leaves is
      much higher than in stems. Picrinine content in leaves was 3.8 times of immature
      stems, ursolic acid and oleanolic acid content were 5.1 and 4.2 times of immature
      stems, respectively. The variety of picrinine content in different batches
      samples was biggest, ursolic acid and oleanolic acid content was relatively
      stable. The overall quality of leaves has an obvious difference compared with the
      immature stems, so the leaves of A. scholaris mix with immature stems could not
      be as Dai medicine in Dai clinic. Infrared spectroscopy combined with
      chromatography can quickly identify different medicinal parts and evaluate
      overall quality of Dai medicine, which can apply to quality control of Dai
      medicine.

PMID- 30192481
TI  - [Study on the Release Process for Lavender Essential Oil Microcapsule by FTIR].
AB  - In order to find out the constitute forms of lavenderessential oil-beta
      cyclodextrin inclusion complex and the process of release of lavenderessential
      oilwith temperature changes, we used Fourier transform infrared spectroscopy
      (FTIR) method to compare and analyze lavender essential oil (LO), beta-
      cyclodextrin (beta-CD) and lavender essential oil microcapsule (LOM), while the
      infrared spectral changes of release process at different temperatures of the oil
      in microcapsulewas analyzed, andthe principal component method was further used
      to explore the physical and chemical stability and release process of LO after it
      was entrapped by beta-CD. The results showed that comparative analysis by
      infrared spectroscopy, characteristic peaks of LO embedded had redshift peak and
      its peak shape became wider, which mainly affected by the formation of molecular
      hydrogen bonds , p-pi conjugate phenomenon and the spatial structure of beta-CD;
      in addition, we set temperature range from 25 to 95 C, the temperature interval
      of 10 C, and then determined LOM by IR spectrum to test and verify physical and
      chemical stability and release conditions of LO which was embedded by beta-CD.
      The results demonstrated that, water molecule inLOM hydrate was easily lost and
      the essential oil component of LOM was in stable physical and chemical
      properties, and the amount of escaping for LO at 95 C was less than 6.5 percent
      when the release was slow; through IR spectra data of variable temperature was
      analyzed under principal component analysis (PCA), We may find that the
      cumulative variance of the first two principal components was 99.3%. And PC1
      ingredient could be considered as the characteristic variable of beta-CD and PC2
      component was the characteristic variable of LO by principal component load
      analysis. The result showed that the release of ester from LOM was faster than
      alcohol. It was simple and efficient by using infrared analysis method to have a
      comprehensive understanding on the physical and chemical stability and the
      release process of the embedded oil, and it will provide a new theoretical
      support for the study on the release process of lavender essential oil
      microcapsule.

PMID- 30192482
TI  - [Rapid Prediction Study of Total Flavonids Content in Panax notoginseng Using
      Infrared Spectroscopy Combined with Chemometrics].
AB  - The variation on origin and growth environment could make a holistic impact on
      the secondary metabolites and quality of traditional Chinese medicine. In recent
      years, the origin of Panax notoginseng is spread from the genuine producing area
      of Wenshan to surrounding cities. The content of three saponins, as an indicator,
      is to ensure the quality of Panax notoginseng in Chinese pharmacopoeia. However,
      a single indicator is limited to comprehensive quality evaluation of Panax
      notoginseng. In this study, the total flavonoids content of Panax notoginseng was
      determinated by ultraviolet-visible (UV-Vis) spectrophotometry, Fourier transform
      infrared (FTIR) spectroscopy combined with chemometrics, as a rapid prediction
      model of total flavonoids content, was establish to provide some basic
      information for rapid and holistic quality assessment of Panax notoginseng. A
      total of 96 UV-Vis and FTIR spectra of Panax notoginseng originated from 12
      regions were collected. The UV-Vis spectra of samples were recorded at 268 nm,
      and the content of total flavonoids was calculated based on standard linear
      equation of rutin. Pre-processing data were calculated with first (1D) and second
      derivative (2D), Savitsky-Golay smoothing with seven, nine, and eleven points.
      2/3 of the 96 individuals were selected to form the training set by using Kennard
      stone algorithm, and the rest were used as prediction set. Training set data were
      used to establish the orthogonal signal correction-partial least squares
      regression (OSC-PLSR) model and the 1/7 cross-validation method was used for
      screening optimal numbers of principal component, the prediction set was utilized
      to verify the accuracy and reliability of the OSC-PLSR model. Results showed
      that: (1) The correlation coefficient r of standard rutin was 0.9997, and the
      linear concentration range was from 5.6 to 72.0 MUg.mL(-1), namely, there were
      good correlation between the absorbance and concentration. (2) The Panax
      notoginseng contained higher content of total flavonoids (more than 7 mg.g(-1))
      in three genuie producing areas of Wenshan, Luoping county and Shilin county. (3)
      After the same points of Savitsky-Golay smoothing, the model predictive ability
      of 2D is better than that of 1D, and the predictive ability of different
      processing model has an obvious difference. (4) In all prediction models, the
      2D+SG 7+OSC-PLSR (R(2)(pre)=0.976 1, RMSEP=0.325 2) and 2D+SG 11+OSC-PLSR
      (R(2)(pre)=0.946 9, RMSEP=0.382 0) model showed an excellent predictive effect,
      the value of RMSEP was below 0.4, and the predicted values were close to the
      detection values. The result indicated that FTIR combined with OSC-PLSR could
      accurately predict the content of total flavonoids. It could provide a rapid,
      simple, and effective method for the holistic quality control of Panax
      notoginseng.

PMID- 30192483
TI  - [Detection of Camellia Oleifera Oil Adulterated with Sunflower Oil with Near
      Infrared (NIR) Spectroscopy and Characteristic Spectra].
AB  - Camellia oleifera oil has the reputation of "oriental olive oil"; it is important
      to detect the adulterated camellia oleifera oil. In this paper, NIR spectra were
      used to detect camellia oleifera oil adulterated with sunflower oil. Camellia
      oleifera oil adulterated with varying mass fraction of sunflower oil were
      prepared, i. e., 11 samples in 0%~10% with the gradient of 1%, 6 samples in
      15%~40% with the gradient of 5%, 6 samples in 50%~100% with the gradient of 10%,
      and all the samples were divided into four groups such as A(0%~5%), B(6%~10%),
      C(15%~40%) and D(50%~100%). A total of 207 absorbance spectra(1 000~2 500 nm)
      were acquired by sampling 9 times in each adulteration. Calibration set was
      consist of two-thirds of the spectra data in each group selected randomly, and
      the validation set was made up of the last spectral data. After removing the
      noise in both ends of the spectra, principal component analysis(PCA) was used to
      reduce the dimensionality, then the first four PCs were used to build the support
      vector machine (SVM) identification model, and the identification accuracies of
      96.38% and 94.20% in calibration and validation set were obtained. Furthermore,
      five characteristic wavelengths (1 212, 1 705, 1 826, 1 905 and 2 148 nm) were
      selected based on the loading of the PCs, the peaks or troughs of the original
      spectra and the chemical functional groups they were corresponding to. A NIR
      simplified SVM identification model was built by them, and the identification
      accuracies were 94.20% and 92.75%. Overall, both NIR spectroscopy and NIR
      characteristic spectra can realize the identification of camellia oleifera oil
      adulterated with sunflower oil, and the characteristic wavelengths, selected in
      this study, provide a basis for the design of corresponding instrument.

PMID- 30192484
TI  - [Spectroscopy Identification of Untreated and Heated Corundum].
AB  - Nowadays, a great quantity of heat treating corundums are emerging in our market.
      It is hard to distinguish them scientifically just by conventional methods. In
      order to accurately determine whether the corundums have been heated or not, we
      need to analyse their spectral characteristics. This paper describes the
      spectroscopy identification of untreated and heated corundum. The experiment is
      conducted as follows: First, We observed the inclusions of corundum samples, then
      measured and recorded their infrared spectra, UV-Vis spectra by Fourier Transform
      Infrared Spectrometer and Ultraviolet-visible Spectrophotometer respectively.
      Next we chose a part of samples to heat, after the heat treatment, we recorded
      their spectra and made a comparison with that of untreated corundums. The results
      showed that we can detect the absorption peaks at 1 980 and 2 110 cm(-1) which
      represent diaspore in untreated ruby. However, after heat treatment, the
      absorption peaks disappear which means the structure of AlO(OH) has been
      destroyed. The sapphires which grown in alkali basalt under reductive condition
      appear the absorption peak at 3 310 cm(-1). However, this peak vanishes after 18
      h heat treatment when the temperature is 1 600 C. For UV-Vis spectra of ruby,
      after heat treatment, the slight shift occurs in strong, wide absorption band at
      around 555 nm, and this band becomes more pointed. In addition, absorption
      intensity difference between wave crest and wave hollow increases. The absorption
      bands at 375, 387, 454 nm of heated sapphires are more pointed than that of the
      untreated sapphires, and absorption intensity difference rises. These changes in
      spectral characteristics can help us to distinguish untreated corundum from heat
      treating corundum.

PMID- 30192485
TI  - [In-Vivo Noninvasive Measurement of Human Blood Glucose Levels by Mid-Infrared
      Spectrograph with External CO(2) Laser Source].
AB  - Diabetes is a kind of diseases which does harm to people's health, and the
      detection of human blood glucose levels utilizing blood samples will result in
      pain even infection for patients. Thus the in-vivo noninvasive measurement of
      human blood glucose levels has vital value in clinical diagnosis, detection and
      therapy, and it also is a very hot research topic with challenging. At present,
      as to various noninvasive detection methods, the technology based on mid-infrared
      absorption spectrophotometry with ATR has been gaining increasing attention.
      However, when carrying out noninvasive measurement of human blood glucose levels
      by means of the spectrophotometry equipped with routine light sources, the
      penetration depth of probe light in human tissues is low and thus it is very
      difficult to reach the stromal layer containing body fluids and especially dermis
      layer containing blood for probe light, which resulting in low relativity between
      experimental data and real human blood glucose levels and thus limiting the
      clinical application. Generally, not only the mid-infrared laser with high
      strength and high purity can deeper penetrate the human tissues, but also the
      output wavelengths at 1 035 cm(-1) of CO2 laser very coincide with the
      fundamental frequency characteristic absorption at 1 029 cm(-1) of glucose. Thus,
      in this work, a novel noninvasive mid-infrared measurement system to detect human
      blood glucose levels has been successfully assembled, in which a CO2 laser was
      used a self-defined external light source of the new mid-infrared absorption
      spectrophotometry with ATR. In this system, the absorbance of human fingertip at
      1 035 cm(-1) has been measured when external CO2 laser source was used as probe
      light, at the same time, the mid-infrared absorption spectra of fingertip have
      been also obtained and absorbance at 1 492 cm(-1) has been recorded. The human
      blood glucose levels were determined synchronously by means of the routine
      medical method. The experimental results showed that the ratio in fingertip
      between absorbance at 1 035 cm(-1) from the laser source and one at 1 492 cm(-1)
      from mid-infrared absorption spectrophotometry could synchronously change with
      the human blood glucose levels, and the ratio presents certain positive
      relativity with the real human blood glucose levels(R=0. 812 5). Thus the
      measurement data could be used as a new index of blood glucose level in human
      body, which showed the potential in clinical diagnosis of the ATR mid-infrared
      absorption spectrophotometry with external CO(2) laser source in noninvasive
      measurement of human blood glucose levels.

PMID- 30192486
TI  - [Research in Magnesite Grade Classification Based on Near Infrared Spectroscopy
      and ELM Algorithm].
AB  - Due to the needs of industrial development, the different content and uncertain
      distribution of magnesite mineral lead to great difficulties in o determining its
      grade, therefore, we propose a combination of near-infrared spectroscopy and the
      ELM magnesite grade classification model. The model can achieve rapid
      classification of magnesite grade. Near infrared spectroscopy, considering that
      different types of H group in magnesite have different absorption degrees to near
      infrared spectroscopy, is used to determine the composition and content of
      magnesite. It is simple, fast, accurate and efficient without destroying the
      sample. In this paper, we take magnesite 30 group from Yingkou City, Liaoning
      Province Dashiqiao for the study, collecting their magnesite NIR data samples at
      30*973, using principal component analysis (PCA) for data dimensionality
      reduction process. The main element contribution rate is greater than 99.99%
      obtained characteristic variables of 10, established quantitative analysis ELM
      algorithm mathematical model, take 20 groups of samples as the training samples
      (including 6 super group, 14 groups non), 10 groups of samples for testing
      samples (including super grade4 groups, 6 groups non), ELM algorithm model hidden
      layer nodes selection 20. In order to further improve the classification
      performance, two kinds improved ELM algorithm models are proposed: conduct
      optimization selection ELM for the traditional ELM input weights and threshold
      using the circulation patterns and integrate integration-Featured ELM based on
      Featured ELM. And compare to which use the artificial method, chemical method and
      BP neural network model approach. The results showed that magnesite grade
      classification with the near-infrared spectroscopy and ELM model have a distinct
      advantage regardless of cost or time, and the accuracy rate can reach over 90%,
      which provides a new way to classify magnesite grade.

PMID- 30192487
TI  - [Application of Intelligent Optimization Algorithms to Wavelength Selection of
      Near-Infrared Spectroscopy].
AB  - Near infrared spectroscopy (NIRS) is a kind of indirect analysis technology,
      whose application depends on the setting up of relevant calibration model. In
      order to improve interpretability, accuracy and modeling efficiency of the
      prediction model, wavelength selection becomes very important and it can minimize
      redundant information of near infrared spectrum. Intelligent optimization
      algorithm is a sort of commonly wavelength selection method which establishes
      algorithm model by mathematical abstraction from the background of biological
      behavior or movement form of material, then iterative calculation to solve
      combinatorial optimization problems. Its core strategy is screening effective
      wavelength points in multivariate calibration modeling by using some objective
      functions as a standard with successive approximation method. In this work, five
      intelligent optimization algorithms, including ant colony optimization (ACO),
      genetic algorithm (GA), particle swarm optimization (PSO), random frog (RF) and
      simulated annealing (SA) algorithm, were used to select characteristic wavelength
      from NIR data of tobacco leaf for determination of total nitrogen and nicotine
      content and together with partial least squares (PLS) to construct multiple
      correction models. The comparative analysis results of these models showed that,
      the total nitrogen optimums models of dataset A and B were PSO-PLS and GA-PLS
      models. GA-PLS and SA-PLS models were the optimums for nicotine, respectively.
      Although not all predicting performance of these optimization models was superior
      to that of full spectrum PLS models, they were simplified greatly and their
      forecasting accuracy, precision, interpretability and stability were improved.
      Therefore, this research will have great significance and plays an important role
      for the practical application. Meanwhile, it could be concluded that the
      informative wavelength combination for total nitrogen were 4 587~4 878 and 6
      700~7 200 cm(-1), and that for tobacco nicotine were 4 500~4 700 and 5 800~6 000
      cm(-1). These selected wavelengths have actually physical significance.

PMID- 30192488
TI  - [CHANGES IN BRAIN ELECTRICAL ACTIVITY PATTERNS IN RATS WITH DIFFERENT
      SUSCEPTIBILITY TO SEIZURES IN LITHIUM-PILOCARPINE MODEL OF STATUS EPILEPTICUS].
AB  - The intracranial EEG was continuously registered in Krushinskii-Molodkina rats
      with inherited susceptibility to audiogenic seizures and in Wistar rats, which
      are resistant to the audiogenic convulsions in the lithium-pilocarpine model of
      status epilepticus (SE). The recordings were done from somatosensory, auditory
      and visual cortical areas, caudate nucleus, hippocampus and dorso-medial nucleus
      of thalamus. We found that SE was induced in Krushinskii-Molodkina rats by
      intramuscular injections of pilocarpine at a minimum dose of 15 mg/kg, while in
      Wistar rats with a dose of 25 mg/kg. We describe six successive EEG patterns
      during SE. We identified behavioral convulsive manifestations associated with
      each phase of the SE. Rats of both strains had the same sequence and the main
      properties of EEG patterns, except the latency of phase 1 (Krushinskii-Molodkina
      rats 13 + 3 min vs. Wistar rats 23 + 2 min). In conclusion, the rats with
      susceptibility to audiogenic seizures have increased sensitivity to the
      pilocarpine, but the development and time-course of SE in rats of both strains
      did not differ.

PMID- 30192491
TI  - [THE INFLUENCE OF SHORT-TIME CEREBRAL ISCHEMIA ON PIAL VESSELS ADRENOREACTIVITY
      IN RATS].
AB  - Reactivity of pial vessels in response to a brain surface irrigation by
      norepinephrine solution in rats, subjected to transient global cerebral ischemia
      (2VO+hypo model), was investigated. Four different groups of rats at 2, 7, 14 or
      21 days after ischemia were subjected to microvascular studies using in vivo
      video microscopy method. The diameter changes of pial arteries and veins in
      response to norepinephrine were measured. It was established that cerebral
      ischemia led to increase the number of the constrictions to norepinephrine mainly
      at the vessels to relating to a group of small pial arteries and arterioles and
      pial veins of the 3rd generation. Reactivity changes were observed in all time
      points studied. These changes probably is connected with caused by ischemia the
      increase in reactivity and sensitivity of pial vessels adrenoceptors. The
      greatest changes are noted in 14 days after ischemia.

PMID- 30192489
TI  - [EFFECT OF QUERCETIN ON NEURODEGENERATIVE AND COMPENSATORY PROCESSES IN
      NIGROSTRIATAL SYSTEM IN A MODEL OF PRECLINICAL PARKINSON''S DISEASE STAGE IN
      RATS].
AB  - Data on HSP70 involvement in Parkinson's disease (PD) pathogenesis, received in
      last 10 years, cannot answer the question whether the decrease in stress
      inducible Hsp70 brain expression is one of the reasons for progressive
      neurodegeneration in PD. In the present study, the inhibitor of HSPs expression
      quercetin was used in a rat model of nigrostriatal system proteasome dysfunction.
      This model was created by the microinjections of the specific proteasome activity
      inhibitor lactacystin, that was injected locally to the substantia nigra pars
      compacta (SNpc). The model reproduces the under-threshold level of nigrostriatal
      degeneration and neurochemical features characteristic of the preclinical PD
      stage. It was shown for the first time that quercetin pretreatment inhibited the
      LC-induced expression of Hsp70 in the SNpc neurons and increased in 1.5 times the
      dopamine (DA)-ergic neurons death and in 2.7 times the striatal DA-ergic axons
      degeneration. These changes were accompanied by the depletion of compensatory
      mechanisms and HSP70 content in the SNpc neurons and the appearance of the motor
      dysfunctions, typical for the clinical PD stage. The results of this
      investigation indicate the important role of Hsp70 in mechanisms of the
      nigrostriatal system protection in proteasome dysfunction, characteristic for the
      pre-clinical PD stage. The data obtained can be considered as the scientific
      basis for the development of new technologies for early PD therapy by exogenous
      Hsp70.

PMID- 30192492
TI  - [Research on Chemical Constituents of Bamboo Fiber Cell Wall Based on Nano-IR
      Technology].
AB  - Nano-IR technology was firstly employed on bamboo fiber research with purpose to
      further understand the fine structure of bamboo fiber cell wall. Chemical
      constituent distribution of bamboo fiber was studied, and the feasibility of the
      novel technology was discussed by comparing with other traditional methods. The
      results showed that Nano-IR technology, which has made a breakthrough on
      diffraction limit of traditional infrared spectroscopy, can acquire nano-scale
      infrared spectrum of bamboo cell wall in situ condition. The characteristic peak
      positions of Nano-IR spectrum is basically the same with that of microscopic FTIR
      spectrum, indicating that Nano-IR spectrum can reveal the chemical information of
      bamboo cell wall. The results of the present work suggested that nano-IR
      technology could be an effective research tool in research of nano chemical
      composition distribution of bamboo cell wall.

PMID- 30192493
TI  - [EFFECT OF T1R3 RECEPTOR PROTEIN DELETION ON GLUCONEOGENESIS AND LIPID METABOLISM
      IN MICE].
AB  - Receptors of the T1R family are molecular sensors for sweet taste stimuli. They
      are expressed not only in the oral cavity, but in most of endocrine cells
      controlling homeostasis of glucose as well as in adipocytes. Earlier, we have
      demonstrated that deletion of the Taslr3 gene, which encodes the T1R3 protein,
      reduces glucose tolerance, elevates insulin resistance and cause a decrease of
      blood glucose level after food deprivation. The goal of the study was to
      elucidate an involvement of T1R3 in control of endogenous glucose synthesis and
      lipid metabolism. Experiments were performed with an inbred mouse strain
      C57BL/6ByJ and the Taslr3-gene knockout strain C57BL/6J-Tas1r3tm1Rfm maintained
      at the normocaloric diet. It was shown in vivo that the presence of intact T1R3
      stimulates gluconeogenesis and lipid utilization during starvation and likely
      promotes glycogen synthesis. Additionally, T1R3 potentiates utilization of
      triglycerides and glycerol (in fed state) and restricts secretion of glucagon
      during fasting but does not affect insulin output. Thus, T1R3-mediated visceral
      reception of metabolites is involved in control of carbohydrate and lipid
      metabolism.

PMID- 30192494
TI  - [Determination of Dibutyl Phthalate Based on Two-Dimensional Correlation Mid
      Infrared Spectroscopy].
AB  - As a kind of Phthalate esters ( PEs ), Di-n-butyl phthalate ( DBP ) is widely
      employed as plasticizers in the production of polymeric materials. The
      concentration variation of DBP/n-hexane solution was studied by monitoring the
      chroma evolution of infrared absorption spectra in conjunction with spectral
      analysis by using two-dimensional-correlation spectroscopy. Absorption peaks at
      742,1 078,1 123,1 281,1 467,1 728,2 873,2 933,2 961 cm(-1) was gained with
      Fourier transform infrared spectra. The IR spectra was divided into three bands:
      400~1 200, 1 200~1 900 and 2 900~4 000 cm(-1), correlation between the absorption
      peaks and the sequential order of the changes in spectral intensity extracted
      from synchronous and asynchronous plots indicated that some bong vibrations in 1
      123 cm(-1) (Benzene ring surface vibration and OCO bending vibration ), 1 728 cm(
      1) (CO bending vibration), 2 873, 2 961 cm(-1) (CH3 concertina movement ) and 3
      436 cm(-1) (C-H bending vibration in plane of Benzene) is sensitive to the
      concentration of DBP. This result showed that the chroma evolution of infrared
      absorption spectra in conjunction with spectral analysis using two-dimensional
      correlation spectroscopy can accurately analyze the concentration of DBP in n
      hexane. This research provides a theoretical basis to the detection and analysis
      of DBP.

PMID- 30192495
TI  - [DYNAMICS DAILY VARIABILITY OF HEART RATE AND BLOOD PRESSURE IN CHRONIC HEART
      FAILURE].
AB  - Analysis of results the telemetry monitoring of daily dynamics of heart rate
      variability in the control and experimental rats with chronic heart failure (CHF)
      has revealed different mechanisms of vegetative regulation of heart rate. In
      animals with chronic heart failure found a significant worsening of cardiac
      dysfunction at night and in the morning, accompanied by an increase in the
      variability of systolic and pulse pressure as well as the number of QTc intervals
      longer than 220 ms and Tpeak-Tend. This indicates the maximal high risk of fatal
      ventricular arrhythmias, leading to sudden cardiac death.

PMID- 30192496
TI  - [SIGNIFICANCE OF OPIOID RECEPTORS IN THE CYTOPROTECTIVE ACTION OF CHRONIC HYPOXIA
      DURING ANOXIA-REOXYGENATION OF CARDIOMYOCYTES].
AB  - It was investigated the role of delta-, MU- i kappa-opioid receptors (ORs) in the
      development of cytoprotective effect of chronic normobaric hypoxia (CNH) using
      anoxia/reoxygenation of isolated cardiomyocytes. Adaptation to CNH was achieved
      by the maintenance of rats for 21 days at atmosphere containing 12% O2.
      Anoxia/reoxygenation of isolated cardiomyocytes of intact rats evoked a death of
      23% cells and enhancement of lactate dehydrogenase (LDH) release from cells.
      Anoxia/reoxygenation of isolated cardiomyocytes of adapting rats induced a death
      of only 2.5% cells and LDH release decreased by 25%. Preliminary incubation of
      cells with the OR blocker naloxone (300 nM) or the delta-OR antagonist TIPP(psi)
      (30 nM) or the selective delta2-OR antagonist naltriben (1 nM) or the MU-OR
      antagonist CTAP (100 nM) 25 min prior to anoxia abolished adaptive enhancement of
      cell survival and a decrease in LDH release. The blocking of delta1-OR by BNTX (1
      nM) or kappa-OR by nor-binaltorphimine (3 nM) not affected on the cytoprotection
      at CNH. Consequently, cardiac cell delta2- and MU-opioid receptors are involved
      in the cytoprotective effect of chronic normobaric hypoxia.

PMID- 30192497
TI  - [INFLUENCE OF HYDROGEN SULFIDE ON BLOOD OXYGEN PARAMETERS DURING HEPATIC ISCHEMIA
      REPERFUSION IN RATS].
AB  - Tissue relative "hyperoxia" during reperfusion can cause oxidative stress due to
      oxygen participation in free radical processes. The influence of the hydrogen
      sulfide on the blood oxygen was investigated during hepatic ischemia(30 min,
      m.Pringle) and reperfusion(120 min) in rats. The parameters of blood oxygen (r50,
      Hb, MetHb, HbCO, pCO2,pO2, pH, TCO2, ABE, SBC), summary nitrite/nitrate level,
      plasma hydrogen sulfide and transaminases (ALT, AST) as a marker of liver damage
      were estimated. It's detected, that a single injection of sodium hydrosulfide (14
      MUmol/kg, 5 min before reperfusion) improves blood oxygen parameters (p50, pH,
      TCO2, ABE, SBC), plasma hydrogen sulfide and decreases transaminase levels during
      hepatic ischemia-reperfusion in rats. It was no changes in the MetHb or HbCO
      concentrations after sodium hydrosulfide infusion. The protective effect of
      hydrogen sulfide can be bind with increased hemoglobin oxygen affinity in the
      blood during reperfusion.

PMID- 30192498
TI  - Immune Adjuvant Targeting Micelles Allow Efficient Dendritic Cell Migration to
      Lymph Nodes for Enhanced Cellular Immunity.
AB  - Cellular immunity is essential for the effectiveness of vaccines against cancer.
      After capture of vaccines, dendritic cells (DCs) have to migrate to lymph nodes
      via chemokine receptor type 7 (CCR7). Subsequently, DCs present cytosolic
      antigens via major histocompatibility complex class I (MHC I) molecules to induce
      cellular immunity. However, various vaccines fail to induce potent cellular
      immunity due to insufficient MHC I-restricted antigen presentation and
      limitations of immune adjuvants. Hence, we constructed novel immune adjuvant
      targeting micelles (M-COSA) to targeted codeliver antigen ovalbumin (OVA) and
      plasmid DNA encoding CCR7 (CCR7 pDNA) to the cytosol of DCs, thus promoting DC
      migration to lymph nodes to boost MHC I-restricted antigen presentation. M-COSA
      exhibited adjuvant activity and demonstrated more efficient DC cellular uptake
      compared with COSA. M-COSA/OVA/pDNA increased costimulatory molecule expression
      and cytokine secretion, resulting in DC activation and maturation. Moreover,
      antigens and pDNA, which were encapsulated in micelles, escaped from the endosome
      into the cytoplasm to achieve MHC I-restricted antigen presentation and increase
      CCR7 expression. The number of CD8+ T cells, which was positively correlated with
      tumor rejection, was notably increased and tumor growth was dramatically
      suppressed after vaccination with M-COSA/OVA/pDNA. In summary, M-COSA/OVA/pDNA
      micelles, which allow DC targeting and efficient DC migration to lymph nodes to
      enhance cellular immunity, exhibit effective tumor inhibition and lay the
      foundation for novel vaccine design.

PMID- 30192499
TI  - Gel-Mediated Electrospray Assembly of Silica Supraparticles for Sustained Drug
      Delivery.
AB  - Supraparticles (SPs) composed of smaller colloidal particles provide a platform
      for the long-term, controlled release of therapeutics in biomedical applications.
      However, current synthesis methods used to achieve high drug loading and those
      involving biocompatible materials are often tedious and low throughput, thereby
      limiting the translation of SPs to diverse applications. Herein, we present a
      simple, effective, and automatable alginate-mediated electrospray technique for
      the assembly of robust spherical silica SPs (Si-SPs) for long-term (>4 months)
      drug delivery. The Si-SPs are composed of either porous or nonporous primary Si
      particles within a decomposable alginate matrix. The size and shape of the Si-SPs
      can be tailored by controlling the concentrations of alginate and silica primary
      particles used and key electrospraying parameters, such as flow rate, voltage,
      and collector distance. Furthermore, the performance (including drug loading
      kinetics, loading capacity, loading efficiency, and drug release) of the Si-SPs
      can be tuned by changing the porosity of the primary particles and through the
      retention or removal (via calcination) of the alginate matrix. The structure and
      morphology of the Si-SPs were characterized by electron microscopy, dynamic light
      scattering, N2 adsorption-desorption analysis, and X-ray photoelectron
      spectroscopy. The cytotoxicity and degradability of the Si-SPs were also
      examined. Drug loading kinetics and loading capacity for six different types of
      Si-SPs, using a model protein drug (fluorescently labeled lysozyme), demonstrate
      that Si-SPs prepared from primary silica particles with large pores can load
      significant amounts of lysozyme (~10 MUg per SP) and exhibit sustained, long-term
      release of more than 150 days. Our experiments show that Si-SPs can be produced
      through a gel-mediated electrospray technique that is robust and automatable
      (important for clinical translation and commercialization) and that they present
      a promising platform for long-term drug delivery.

PMID- 30192500
TI  - Multiphoton Microscopy of pi-Conjugated Copolymers and Copolymer/Fullerene Blends
      for Organic Photovoltaic Applications.
AB  - Organic photovoltaic (OPV) cells based on pi-conjugated copolymer/fullerene
      blends are devices with the highest power conversion efficiencies within the
      class of organic semiconductors. Although a number of image microscopies have
      been applied to films of pi-conjugated copolymers and their fullerene blends,
      seldom have they been able to detect microscopic defects in the blend films. We
      have applied multiphoton microscopy (MPM) using a 65 fs laser at 1.56 MUm for
      spectroscopy and mapping of films of various pi-conjugated copolymers and their
      fullerene blends. All pristine copolymer films have shown third harmonic
      generation (THG) and two-photon or three-photon photoluminescence that could be
      used for mapping the films with micrometer spatial resolution. Since the
      fullerenes have much weaker THG efficiency than those of the copolymers, we could
      readily map the copolymer/fullerene blend films that showed interpenetrating
      micron-sized grains of the two constituents. In addition, we also found second
      harmonic generation from various micron-sized defects in the films that are
      formed during film deposition or light illumination at ambient conditions, which
      do not possess inversion symmetry. The MPM method is therefore beneficial for
      organic films and devices for investigating the properties and growth of
      copolymer/fullerene blends for OPV applications.

PMID- 30192501
TI  - Enhancing the Photoelectrochemical Response of DNA Biosensors Using Wrinkled
      Interfaces.
AB  - Photoelectrochemical (PEC) biosensors, with optical biasing and electrochemical
      readout, are expected to enhance the limit-of-detection of electrochemical
      biosensors by lowering their background signals. However, when PEC transducers
      are functionalized with biorecognition layers, their current significantly
      decreases, which reduces their signal-to-noise ratio and dynamic range. Here, we
      develop and investigate a wrinkled conductive scaffold for loading photoactive
      quantum dots into an electrode. The wrinkled photoelectrodes demonstrate an order
      of magnitude enhancement in the magnitude of the transduced PEC current compared
      to their planar counterparts. We engineer PEC biosensors by functionalizing the
      wrinkled photoelectrodes with nucleic acid capture probes. We challenge the
      sensitivity of the wrinkled and planar biosensors with various concentrations of
      DNA target and observe a 200 times enhancement in the limit-of-detection for
      wrinkled versus planar electrodes. In addition to enhanced sensitivity, the
      wrinkled PEC biosensors are capable of distinguishing between fully complementary
      and targets with a single base-pair mismatch, demonstrating the suitability of
      these biosensors for use in clinical diagnostics.

PMID- 30192502
TI  - Eliminating Light-Soaking Instability in Planar Heterojunction Perovskite Solar
      Cells by Interfacial Modifications.
AB  - Stability remains as a challenge of perovskite solar cells although encouraging
      progress has been made toward their maximum achievable power conversion
      efficiency in recent years. Light-soaking issue, where the device performance
      improves upon continuous light illumination and reduces upon storage in dark, is
      widely observed and marked as the early-stage instability during device
      operation. In this work, we have employed conjugated polymer PCDTBT as the dopant
      free hole-transport layer to fabricate devices without hysteresis but with
      reversible light-soaking instability. The introduction of n-type molecules,
      either organic molecule PDI2 or fullerene derivative PC61BM, as the interfacial
      layer between TiO2 and perovskite layers can effectively reduce or eliminate this
      instability owing to the efficient charge transport and defect passivation at the
      electron-transport layer interface, accompanied with an efficiency of 15.7 and
      17.7%, respectively. We conclude that the light-soaking instability of these
      perovskite solar cells is mainly originated from the charge accumulation at the
      TiO2/perovskite interface and can be eliminated once the interfacial charge can
      be suppressed by interfacial modifications to improve charge transport at the
      interface.

PMID- 30192503
TI  - Anion-Induced Electron Transfer.
AB  - As counterintuitive as it might seem, in aprotic media, electron transfer (ET)
      from strong Lewis basic anions, particularly F-, OH-, and CN-, to certain pi
      acids (piA) is not only spectroscopically evident from the formation of
      paramagnetic piA*- radical anions and piA2- dianions, but also thermodynamically
      justified because these anions' highest occupied molecular orbitals (HOMOs) lie
      above the pi-acids' lowest unoccupied molecular orbitals (LUMOs) creating
      negative free energy changes (Delta G degrees ET < 0). Depending on the relative
      HOMO and LUMO energies of participating anions and pi-acids, respectively, the
      anion-induced ET (AIET) events take place either in the ground state or upon
      photosensitization of the pi-acids. The mild basic and charge-diffuse anions with
      lower HOMO levels fail to trigger ET, but they often form charge transfer (CT)
      and anion-pi complexes. Owing to their high HOMO levels in aprotic environments,
      strong Lewis basic anions, such as F- enjoy much greater ET driving force (Delta
      G degrees ET) than mild and non-basic anions, such as iodide. In protic solvents,
      however, the former become more solvated and stabilized and lose their electron
      donating ability more than the latter, creating an illusion that F- is a poor
      electron donor due to the high electronegativity of fluorine. However, UV-vis,
      EPR, and NMR studies consistently show that in aprotic environments, F- reduces
      essentially any pi-acid with LUMO levels of -3.8 eV or less, revealing that
      contrary to a common perception, the electron donating ability of F- anion is not
      dictated by the electronegativity of fluorine atom but is a true reflection of
      high Lewis basicity of the anion itself. Thus, the neutral fluorine atoms with
      zero formal charge and F- anion have little in common when it comes to their
      electronic properties. The F- anion can also legitimately act as a Bronsted base
      when the proton source has a p Ka lower than that of its conjugate acid HF (15),
      not the other way around, and ET from F- to a poor electron acceptor is not
      thermodynamically feasible. While there is no shortage of indisputable evidence
      and clear-cut thermodynamic justifications for ET from F- and other Lewis basic
      anions to various pi-acids in aprotic solvents, because of the aforesaid
      misconception, it had been posited that F- perhaps formed diamagnetic
      Meisenheimer complexes via nucleophilic attack, deprotonated an aprotic solvent
      DMSO against an insurmountably high p Ka (35) leading to a pi-acid reduction, or
      formed [F-/piA*+] complexes via a thermodynamically prohibited oxidation of pi
      acids. Unlike AIET, however, none of these hypotheses was thermodynamically
      viable nor supported by any experimental evidence. First, by defining the
      thermodynamic criteria of AIET pathways and all other alternate hypotheses and
      then evaluating the spectroscopic signals emanating from the interactions between
      different anions and pi-acids and Lewis acids in the light of these criteria,
      this Account comes to a conclusion that AIET is the only viable mechanism that
      can rationalize the reduction of pi-acids without violating any thermodynamic
      rules. The paradigm-shifting discovery of AIET not only exposed a common
      misconception about the electron donating ability of F- but also enabled naked
      eye detection of toxic anions, electrode-free silver plating, luminescent silver
      nanoparticle synthesis, light-harvesting, and conductivity enhancement of
      conjugated polymers, with more innovative applications still to come.

PMID- 30192504
TI  - Deep-Blue Oxadiazole-Containing Thermally Activated Delayed Fluorescence Emitters
      for Organic Light-Emitting Diodes.
AB  - A series of four novel deep-blue to sky-blue thermally activated delayed
      fluorescence (TADF) emitters (2CzdOXDMe, 2CzdOXD4MeOPh, 2CzdOXDPh, and
      2CzdOXD4CF3Ph) have been synthesized and characterized. These oxadiazole-based
      emitters demonstrated bluer emission compared with the reference emitter 2CzPN
      thanks to the weaker acceptor strength of the oxadiazole moieties. The oxadiazole
      compounds doped in hosts (mCP and PPT) emitted from 435 to 474 nm with
      photoluminescence quantum yields ranging from 14-55%. The emitters possess
      singlet-triplet excited-state energy gaps (Delta EST) between 0.25 and 0.46 eV
      resulting in delayed components ranging from 4.8 to 25.8 ms. The OLED device with
      2CzdOXD4CF3Ph shows a maximum external quantum efficiency of 11.2% with a sky
      blue emission at CIE of (0.17, 0.25), while the device with 2CzdOXD4MeOPh shows a
      maximum external quantum efficiency of 6.6% with a deep-blue emission at CIE of
      (0.15, 0.11).

PMID- 30192505
TI  - Critical Role of the Chemical Environment of Interlayer Na Sites: An Effective
      Way To Improve the Na Ion Electrode Activity of Layered Titanate.
AB  - The chemical environments of the interlayer Na sites of layered titanate are
      finely controlled by the intercalation of n-alkylamine with various alkyl chain
      lengths to explore an effective way to improve its electrode functionality for
      sodium-ion batteries (SIBs). The n-alkylamine intercalation via ion-exchange and
      exfoliation-restacking routes allows the modification of in-plane structures of
      layered titanate to be tuned. Among the present n-alkylamine-intercalates, the n
      pentylamine-intercalated titanate shows the largest discharge capacity with the
      best rate characteristics, underscoring the critical role of optimized
      intracrystalline structure in improving the SIB electrode performance of layered
      titanate. The creation of turbostratic in-plane structure degrades the SIB
      electrode performance of layered titanate, indicating the detrimental effect of
      in-plane structural disorder on electrode activity. 23Na magic-angle spinning
      nuclear magnetic resonance spectroscopy demonstrates that the n-alkylamine
      intercalated titanates possess two different interlayer Na+ sites near ammonium
      head groups/titanate layers and near alkyl chains. The intercalation of long
      chain molecules increases the population of the latter site and the overall
      mobility of Na+ ions, which is responsible for the improvement of electrode
      activity upon n-alkylamine intercalation. The present study highlights that the
      increased population of interlayer metal sites remote from the host layers is
      effective in improving the electrode functionality of layered metal oxide for
      SIBs and multivalent ion batteries.

PMID- 30192506
TI  - Tissue Plasminogen Activator-Porous Magnetic Microrods for Targeted Thrombolytic
      Therapy after Ischemic Stroke.
AB  - Tissue plasminogen activator (tPA) is the only FDA approved thrombolytic drug for
      acute ischemic stroke but concerns regarding its limitations remain. Here, we
      developed a new strategy by incorporating tPA into porous magnetic iron oxide
      (Fe3O4)-microrods (tPA-MRs) for targeted thrombolytic therapy in ischemic stroke
      induced by distal middle cerebral artery occlusion. We showed that intra-arterial
      injection of tPA-MRs could target the cerebral blood clot in vivo under the
      guidance of an external magnet, where tPA was subsequently released at the site
      of embolism. When applied with an external rotating magnetic field, rotating tPA
      MRs significantly improved not only the mass transport of the tPA-clot reaction,
      but also mechanically disrupted the clot network, which thus increased clot
      interaction and penetration of tPA. Importantly, intravenously injected MRs could
      be discharged from the kidney, and the function of liver and kidney were not
      damaged at different durations after administration of tPA-MRs. Our data suggest
      that tPA-MRs overcome the limitations of thrombolytic therapy with tPA alone,
      which may be not only just for the treatment of ischemic stroke but also have
      majorly impact on other thrombotic diseases.

PMID- 30192507
TI  - MoS2 Memristors Exhibiting Variable Switching Characteristics toward Biorealistic
      Synaptic Emulation.
AB  - Memristors based on 2D layered materials could provide biorealistic ionic
      interactions and potentially enable construction of energy-efficient artificial
      neural networks capable of faithfully emulating neuronal interconnections in
      human brains. To build reliable 2D-material-based memristors suitable for
      constructing working neural networks, the memristive switching mechanisms in such
      memristors need to be systematically analyzed. Here, we present a study on the
      switching characteristics of the few-layer MoS2 memristors made by mechanical
      printing. First, two types of dc-programmed switching characteristics, termed
      rectification-mediated and conductance-mediated behaviors, are observed among
      different MoS2 memristors, which are attributed to the modulation of MoS2/metal
      Schottky barriers and redistribution of vacancies, respectively. We also found
      that an as-fabricated MoS2 memristor initially exhibits an analog pulse
      programmed switching behavior, but it can be converted to a quasi-binary
      memristor with an abrupt switching behavior through an electrical stress process.
      Such a transition of switching characteristics is attributed to field-induced
      agglomeration of vacancies at MoS2/metal interfaces. The additional Kelvin probe
      force microscopy, Auger electron spectroscopy analysis, and electronic
      characterization results support this hypothesis. Finally, we fabricated a
      testing device consisting of two adjacent MoS2 memristors and demonstrated that
      these two memristors can be ionically coupled to each other. This device
      interconnection scheme could be exploited to build neural networks for emulating
      ionic interactions among neurons. This work advances the device physics for
      understanding the memristive properties of 2D-material-based memristors and
      serves as a critical foundation for building biorealistic neuromorphic computing
      systems based on such memristors.

PMID- 30192508
TI  - On the Infectivity of Bacteriophages in Polyelectrolyte Multilayer Films:
      Inhibition or Preservation of Their Bacteriolytic Activity?
AB  - Antibiotic resistance in bacterial cells has motivated the scientific community
      to design new and efficient (bio)materials with targeted bacteriostatic and/or
      bactericide properties. In this work, a series of polyelectrolyte multilayer
      films differing in terms of polycation-polyanion combinations are constructed
      according to the layer-by-layer deposition method. Their capacities to host T4
      and phix174 phage particles and maintain their infectivity and bacteriolytic
      activity are thoroughly examined. It is found that the macroscopic
      physicochemical properties of the films, which includes film thickness, swelling
      ratio, or mechanical stiffness (as derived by atomic force microscopy and
      spectroscopy measurements), do not predominantly control the selectivity of the
      films for hosting infective phages. Instead, it is evidenced that the intimate
      electrostatic interactions locally operational between the loaded phages and the
      polycationic and polyanionic PEM components may lead to phage activity reduction
      and preservation/enhancement, respectively. It is argued that the underlying
      mechanism involves the screening of the phage capsid receptors (operational in
      cell recognition/infection processes) because of the formation of either polymer
      phage hetero-assemblies or polymer coating surrounding the bioactive phage
      surface.

PMID- 30192509
TI  - Unbiased Mass Spectrometry Elucidation of the Targets and Mechanisms of Activity
      Based Probes: A Case Study Involving Sulfonyl Fluorides.
AB  - The elucidation of protein/drug interactions remains a major challenge in drug
      discovery. Liquid chromatography-tandem mass spectrometry has emerged as a
      tremendously powerful technology for this endeavor, but its full potential has
      yet to be realized owing in part to unresolved challenges in data analysis.
      Herein, we demonstrate how tandem mass spectrometry can comprehensively map small
      molecule/peptide adducts when combined with unconstrained sequencing. Using a
      published sulfonyl fluoride activity-based probe as a model system, this method
      enabled the discovery of several unreported sites of interaction with its target
      proteins. Crucially, this probe was found to undergo quantitative displacement
      and hydrolysis from the target protein's active site. Isotopic labeling
      experiments provided a mechanistic rationale for the observed hydrolysis that
      involves neighboring-group participation. A chemical biology tagging strategy
      that leverages the probe's observed lability was developed and shown to be
      compatible with the original small molecule inhibitor in discovery profiling
      experiments.

PMID- 30192510
TI  - General Post-annealing Method Enables High-Efficiency Two-Dimensional Perovskite
      Solar Cells.
AB  - Two-dimensional (2D) perovskites, with a formula of (RNH3)2MA n-1Pb nI3 n+1, have
      shown impressive photovoltaic device efficiency with improved stability. The
      operating mechanism of such photovoltaic devices is under debate and the scope of
      incorporated organic cations (RNH3+) is limited. We report a general post
      annealing method to incorporate a variety of organic cations into 2D perovskites,
      which demonstrate significant device efficiencies (7-12%). A detailed
      investigation of the archetypical (C4H9NH3)2MA3Pb4I13 ( n = 4) reveals that such
      perovskites thin films contain multiple 2D phases (i.e., 2D quantum wells, n = 2,
      3, 4, ...). These phases appear to be distributed with decreasing n values from
      the top to the bottom of the 2D perovskites thin film, enabling efficient energy
      transfer in the first 500 ps and possible charge transfer at longer time scale,
      thereby accounting for high device efficiencies. Our post-annealing method is
      compatible with ambient condition and only requires relatively low annealing
      temperature for a very short period of time, offering significant prospects for
      scalable manufacturing of 2D perovskites solar cells.

PMID- 30192511
TI  - Organic-Inorganic Layered and Hollow Tin Bromide Perovskite with Tunable
      Broadband Emission.
AB  - Recently, layered perovskites attracted great attention for its excellent
      stability and light-emitting property. However, most of them rely on the toxic
      element lead and their emission quantum yields are generally low. Here, a unique
      hollow two-dimensional perovskite was developed in which the organic
      hexamethylene diamines (C6H18N22+) strongly coupled with distorted tin bromide
      anions (SnBr64-). This toxic-free low-dimensional tin perovskite exhibits a
      broadband emission in the visible region with a high luminescence quantum yield
      of 86%. First-principles calculation indicate the broadband emission is
      associated with the recombination of self-trapped excitons. And the emission is
      related to the geometry of tin bromide anions. An ultraviolet light-pumped white
      light emitting diode with excellent color-rendering index of 94 was fabricated
      using it together with a commercially available blue phosphor.

PMID- 30192512
TI  - Peptides as Bio-Inspired Electronic Materials: An Electrochemical and First
      Principles Perspective.
AB  - Molecular electronics is at the forefront of interdisciplinary research, offering
      a significant extension of the capabilities of conventional silicon-based
      technology as well as providing a possible stand-alone alternative. Bio-inspired
      molecular electronics is a particularly intriguing paradigm, as charge transfer
      in proteins/peptides, for example, plays a critical role in the energy storage
      and conversion processes for all living organisms. However, the structure and
      conformation of even the simplest protein is extremely complex, and therefore,
      synthetic model peptides comprising well-defined geometry and predetermined
      functionality are ideal platforms to mimic nature for the elucidation of
      fundamental biological processes while also enhancing the design and development
      of single-peptide electronic components. In this Account, we first present
      intramolecular electron transfer within two synthetic peptides, one with a well
      defined helical conformation and the other with a random geometry, using
      electrochemical techniques and computational simulations. This study reveals two
      definitive electron transfer pathways (mechanisms), the natures of which are
      dependent on secondary structure. Following on from this, electron transfer
      within a series of well-defined helical peptides, constrained by either Huisgen
      cycloaddition, ring-closing metathesis, or a lactam bridge, was determined. The
      electrochemical results indicate that each constrained peptide, in contrast to a
      linear counterpart, exhibits a remarkable shift of the formal potential to the
      positive (>460 mV) and a significant reduction of the electron transfer rate
      constant (up to 15-fold), which represent two distinct electronic "on/off"
      states. High-level calculations demonstrate that the additional backbone rigidity
      provided by the side-bridge constraints leads to an increased reorganization
      energy barrier, which impedes the vibrational fluctuations necessary for
      efficient intramolecular electron transfer through the peptide backbone. Further
      calculations reveal a clear mechanistic transition from hopping to superexchange
      (tunneling) stemming from side-bridge gating. We then extended our research to
      fine-tuning of the electronic properties of peptides through both structural and
      chemical manipulation, to reveal an interplay between electron-rich side chains
      and backbone rigidity on electron transfer. Further to this, we explored the
      possibility that the side-bridge constraints present in our synthetic peptides
      provide an additional electronic transport pathway, which led to the discovery of
      two distinct forms of quantum interferometer. The effects of destructive quantum
      interference appear essentially through both the backbone and an alternative
      tunneling pathway provided by the side bridge in the constrained beta-strand
      peptide, as evidenced by a correlation between electrochemical measurements and
      conductance simulations for both linear and constrained beta-strand peptides. In
      contrast, an interplay between quantum interference effects and vibrational
      fluctuations is revealed in the linear and constrained 310-helical peptides.
      Collectively, these exciting findings augment our fundamental knowledge of charge
      transfer dynamics and kinetics in peptides and also open up new avenues to design
      and develop functional bio-inspired electronic devices, such as on/off switches
      and quantum interferometers, for practical applications in molecular electronics.

PMID- 30192513
TI  - Mapping Transient Protein Interactions at the Nanoscale in Living Mammalian
      Cells.
AB  - Protein-protein interactions (PPIs) form the basis of cellular processes,
      regulating cell behavior and fate. PPIs can be extremely transient in nature,
      which hinders their detection. In addition, traditional biochemical methods
      provided limited information on the spatial distribution and temporal dynamics of
      PPIs that is crucial for their regulation in the crowded cellular environment.
      Given the pivotal role of membrane micro- and nanodomains in the regulation of
      PPIs at the plasma membrane, the development of methods to visualize PPIs with a
      high spatial resolution is imperative. Here, we present a super-resolution
      fluorescence microscopy technique that can detect and map short-lived transient
      protein-protein interactions on a nanometer scale in the cellular environment.
      This imaging method is based on single-molecule fluorescence microscopy and
      exploits the effect of the difference in the mobility between cytosolic and
      membrane-bound proteins in the recorded fluorescence signals. After the
      development of the proof of concept using a model system based on membrane-bound
      modular protein domains and fluorescently labeled peptides, we applied this
      imaging approach to investigate the interactions of cytosolic proteins involved
      in the epidermal growth factor signaling pathway (namely, Grb2, c-Raf, and
      PLCgamma1). The detected clusters of Grb2 and c-Raf were correlated with the
      distribution of the receptor at the plasma membrane. Additionally, the
      interactions of wild type PLCgamma1 were compared with those detected with
      truncated mutants, which provided important information regarding the role played
      by specific domains in the interaction with the membrane. The results presented
      here demonstrate the potential of this technique to unravel the role of membrane
      heterogeneity in the spatiotemporal regulation of cell signaling.

PMID- 30192514
TI  - Correction to Highly Sensitive Multifilament Fiber Strain Sensors with Ultrabroad
      Sensing Range for Textile Electronics.

PMID- 30192515
TI  - Impact of Shell Growth on Recombination Dynamics and Exciton-Phonon Interaction
      in CdSe-CdS Core-Shell Nanoplatelets.
AB  - We investigate the impact of shell growth on the carrier dynamics and exciton
      phonon coupling in CdSe-CdS core-shell nanoplatelets with varying shell
      thickness. We observe that the recombination dynamics can be prolonged by more
      than one order of magnitude, and analyze the results in a global rate model as
      well as with simulations including strain and excitonic effects. We reveal that
      type I band alignment in the hetero platelets is maintained at least up to three
      monolayers of CdS, resulting in approximately constant radiative rates. Hence,
      observed changes of decay dynamics are not the result of an increasingly
      different electron and hole exciton wave function delocalization as often
      assumed, but an increasingly better passivation of nonradiative surface defects
      by the shell. Based on a global analysis of time-resolved and time-integrated
      data, we recover and model the temperature dependent quantum yield of these
      nanostructures and show that CdS shell growth leads to a strong enhancement of
      the photoluminescence quantum yield. Our results explain, for example, the very
      high lasing gain observed in CdSe-CdS nanoplatelets due to the type I band
      alignment that also makes them interesting as solar energy concentrators.
      Further, we reveal that the exciton-LO-phonon coupling is strongly tunable by the
      CdS shell thickness, enabling emission line width and coherence length control.

PMID- 30192516
TI  - Hybrid Hydrogel with High Water Vapor Harvesting Capacity for Deployable Solar
      Driven Atmospheric Water Generator.
AB  - The Earth's atmosphere holds approximately 12 900 billion tons of fresh water
      distributed all over the world with fast replenishment. Atmospheric water
      harvesting is emerging as a promising strategy for clean water production in arid
      regions, land-locked areas, and remote communities. The water vapor sorbent is
      the key component for atmospheric water harvesting devices based on absorbing
      releasing process. In this work, a flexible hybrid photothermal water sorbent
      composed of deliquescent salt and hydrogel was rationally fabricated. It
      possesses superior water sorption capacity even in low humidity air thanks to the
      deliquescent salt and maintains a solid form after it sorbs a large amount of
      water owing to the hydrogel platform. The harvested water could be easily
      released under regular sunlight via the photothermal effect, and it can be
      directly reused without noticeable capacity fading. An "easy-to-assemble-at
      household" prototype device with 35 g of the dry hydrogel was tested outdoors
      under field conditions and delivered 20 g of fresh water within 2.5 h under
      natural sunlight. It is estimated that the material cost of making such a device
      to supply minimum daily water consumption for an adult (i.e., 3 kg) is only $3.20
      (USD). This type of atmospheric water generator (AWG) is cheap and affordable,
      works perfectly with a broad range of humidity, does not need any electricity,
      and thus is especially suitable for clean water production in remote areas.

PMID- 30192517
TI  - Development of a Luminescent Dinuclear Ir(III) Complex for Ultrasensitive
      Determination of Pesticides.
AB  - To improve the G-quadruplex specificity of Ir(III) complexes, a novel dinuclear
      Ir(III) complex (Din Ir(III)-1) was designed and synthesized through connecting
      two mononuclear Ir(III) complexes via a diphenyl bridge. Din Ir(III)-1 presents
      3.4-4.1-fold enhancements for G-quadruplex relative to ssDNA and 4.3-5.3-fold
      enhancements relative to dsDNA in luminescence intensity, respectively,
      demonstrating an excellent G-quadruplex selectivity. Ascribed to its superior
      specificity to G-quadruplex, Din Ir(III)-1 was employed to construct a highly
      sensitive luminescent pesticides' detection platform. The detection is based on
      acetylcholinesterase (AChE)-catalyzed hydrolysis product-induced DNA
      conformational transformation and subsequent terminal deoxynucleotidyl
      transferase (TdT) directed G-quadruplex formation. The assay exhibited a linear
      response between the emission intensity of Din Ir(III)-1 and the pesticide
      concentration in the range of 0.5-25 MUg/L ( R2 = 0.994), and the limit of
      detection for the pesticide was as low as 0.37 MUg/L when using aldicarb as the
      model pesticide. Moreover, this strategy demonstrates good applicability for the
      pesticide detection in real samples. It is also versatile for the detection of
      other organophosphate or carbamate pesticides, which have the inhibition ability
      toward AChE. Therefore, the proposed approach is scalable for practical
      application in food safety and environmental monitoring fields and will provide
      promising solutions for the assay of pesticide residues.

PMID- 30192518
TI  - Post-Transcriptional Regulation of tRNA Pools To Govern the Central Dogma: A
      Perspective.
AB  - Since their initial discovery, tRNAs have risen from sole adapter molecules
      during protein synthesis to pivotal modulators of gene expression. Through their
      many interactions with tRNA-associated protein factors, they play a central role
      in maintaining cell homeostasis, especially regarding the fine-tuning in response
      to a rapidly changing cellular environment. Here, we provide a perspective on
      current tRNA topics with a spotlight on the regulation of post-transcriptional
      shaping of tRNA molecules. First, we give an update on aberrant structural
      features that a yet functional fraction of mitochondrial tRNAs can exhibit. Then,
      we outline several aspects of the regulatory contribution of ribonucleases with a
      focus on tRNA processing versus tRNA elimination. We close with a comment on the
      possible consequences for the intracellular examination of nascent tRNA
      precursors regarding respective processing factors that have been shown to
      associate with the tRNA transcription machinery in alternative moonlighting
      functions.

PMID- 30192519
TI  - Quantitation of Intact Proteins in Human Plasma Using Top-Down Parallel Reaction
      Monitoring-MS.
AB  - Direct quantitation of proteins in complex biological matrices by mass
      spectrometry remains a challenge. Here, we describe a novel top-down parallel
      reaction monitoring-mass spectrometry (PRM-MS) assay, enabled by microflow LC
      nanospray MS using a silicon microfluidic LC-MS chip. We demonstrated direct
      analysis of intact proteins such as somatropin in human plasma, achieving
      sensitivity (0.1-1.0 fmole) and speed (1-5 min) on par with enzyme-linked
      immunosorbent assay (ELISA).

PMID- 30192520
TI  - Accretion Product Formation from Ozonolysis and OH Radical Reaction of alpha
      Pinene: Mechanistic Insight and the Influence of Isoprene and Ethylene.
AB  - alpha-Pinene (C10H16) represents one of the most important biogenic emissions in
      the atmosphere. Its oxidation products can significantly contribute to the
      secondary organic aerosol (SOA) formation. Here, we report on the formation
      mechanism of C19 and C20 accretion products from alpha-pinene oxidation, which
      are believed to be efficient SOA precursors. Measurements have been performed in
      a free-jet flow system. Detection of RO2 radicals and accretion products was
      carried out by recent mass spectrometric techniques using different ionization
      schemes. Observed C10-RO2 radicals from alpha-pinene ozonolysis were O,O
      C10H15(O2) xO2 with x = 0, 1, 2, 3 and from the OH radical reaction HO
      C10H16(O2)alphaO2 with alpha = 0, 1, 2. All detected C20 accretion products can
      be explained via the accretion reaction RO2 + R'O2 -> ROOR' + O2 starting from
      the measured C10-RO2 radicals. We speculate that C19 accretion products are
      formed in an analogous way assuming CH2O elimination. Addition of isoprene
      (C5H8), producing C5-RO2 radicals, leads to C15 accretion products formed via
      cross-reactions with C10-RO2 radicals. This process is competing with the
      formation of C19/C20 products from the pure alpha-pinene oxidation. A similar
      behavior has been observed for ethylene additives that form C12 accretion
      products. In the atmosphere, a complex accretion product spectrum from self- and
      cross-reactions of available RO2 radicals can be expected. Modeling atmospheric
      conditions revealed that C19/C20 product formation is only reduced by a factor of
      1.2 or 3.6 in isoprene-dominated environments assuming a 2- or 15-fold isoprene
      concentration over alpha-pinene, respectively, as present in different forested
      areas.

PMID- 30192521
TI  - High-Throughput Separation, Trapping, and Manipulation of Single Cells and
      Particles by Combined Dielectrophoresis at a Bipolar Electrode Array.
AB  - Microfluidic systems have been developed widely in scaled-down processes of
      laboratory techniques, but they are usually limited in achieving stand-alone
      functionalities. It is highly desirable to exploit an integrated microfluidic
      device with multiple capabilities such as cell separation, single-cell trapping,
      and cell manipulation. Herein, we reported a microfluidic platform integrated
      with actuation electrodes, for separating cells and microbeads, and bipolar
      electrodes, for trapping, rotating, and propelling single cells and microbeads.
      The separation of cells and microbeads can be first achieved by deflective
      dielectrophoresis (DEP) barriers. Trapping experiments with yeast cells and
      polystyrene (PS) microbeads suspended in aqueous solutions with different
      conductivities were then conducted, showing that both cells and particles can be
      trapped at the center of wireless electrodes by negative DEP force. Upon
      application of a rotating electric field, yeast cells exhibit translational
      movement along the electrode edges, and self-rotation is seen at an array of
      bipolar electrodes when electrorotational torque and traveling wave DEP force are
      applied on the cells. The current approach allows us to switch the propulsion and
      rotation direction of cells by varying the frequency of the applied electric
      field. Beyond the achievements of single-cell manipulation, this system permits
      effective control of several particles or cells simultaneously. The integration
      of parallel sorting and single trapping stages within a microfluidic chip enables
      the prospect of high-throughput cell separation, single trapping, and large-scale
      cell locomotion and rotation in a noninvasive and disposable format, showing
      great potential in single-cell analysis, targeted drug delivery, and surgery.

PMID- 30192522
TI  - Chitosan: The One and Only? Aminated Cellulose as an Innovative Option for
      Primary Amino Groups Containing Polymers.
AB  - The aim of this study was the synthesis and in vitro characterization of aminated
      cellulose as alternative excipient to chitosan. The aldehyde form of cellulose
      was generated via the oxidative cleavage of vicinal diols by the addition of
      increasing concentrations of sodium periodate. The insertion of primary amines
      was achieved by reductive amination with ammonia. The degree of substitution was
      calculated via primary amino group quantification using a 2,4,6
      trinitrobenzenesulfonic acid assay. Mucoadhesiveness was examined by adopting the
      rotating-cylinder method and tensile studies using porcine intestinal mucosa.
      Hydration was evaluated at pH 2-11. The successful formation of aldehydes as well
      as a subsequent introduction of up to 311.61 micromoles per gram of primary
      amines were proven to correlate with the amount of added periodate. There was a 3
      to 14-fold prolongation in the mucosal residence time of the new polymer in
      comparison to chitosan, as measured by the rotating-cylinder method. Although
      cationic cellulose did not reach the maximum detachment force of chitosan, the
      total work of adhesion of the newly synthesized cellulose derivate was higher
      than that of chitosan. The higher the degree of amination, the higher the degree
      of hydration in neutral and alkaline aqueous media was. Compared to chitosan, the
      novel cationic cellulose derivative displays improved mucoadhesive properties as
      well as sufficient hydration at physiological pH. Therefore, aminated cellulose
      is a promising alternative to the cationic polymers, such as chitosan, used thus
      far.

PMID- 30192523
TI  - Targeting Metalloenzymes for Therapeutic Intervention.
AB  - Metalloenzymes are central to a wide range of essential biological activities,
      including nucleic acid modification, protein degradation, and many others. The
      role of metalloenzymes in these processes also makes them central for the
      progression of many diseases and, as such, makes metalloenzymes attractive
      targets for therapeutic intervention. Increasing awareness of the role
      metalloenzymes play in disease and their importance as a class of targets has
      amplified interest in the development of new strategies to develop inhibitors and
      ultimately useful drugs. In this Review, we provide a broad overview of several
      drug discovery efforts focused on metalloenzymes and attempt to map out the
      current landscape of high-value metalloenzyme targets.

PMID- 30192524
TI  - Patterns of Host-Associated Fecal Indicators Driven by Hydrology, Precipitation,
      and Land Use Attributes in Great Lakes Watersheds.
AB  - Fecal contamination from sewage and agricultural runoff is a pervasive problem in
      Great Lakes watersheds. Most work examining fecal pollution loads relies on
      discrete samples of fecal indicators and modeling land use. In this study, we
      made empirical measurements of human and ruminant-associated fecal indicator
      bacteria and combined these with hydrological measurements in eight watersheds
      ranging from predominantly forested to highly urbanized. Flow composited river
      samples were collected over low-flow ( n = 89) and rainfall or snowmelt runoff
      events ( n = 130). Approximately 90% of samples had evidence of human fecal
      pollution, with highest loads from urban watersheds. Ruminant indicators were
      found in ~60-100% of runoff-event samples in agricultural watersheds, with
      concentrations and loads related to cattle density. Rain depth, season,
      agricultural tile drainage, and human or cattle density explained variability in
      daily flux of human or ruminant indicators. Mapping host-associated indicator
      loads to watershed discharge points sheds light on the type, level, and possible
      health risk from fecal pollution entering the Great Lakes and can inform total
      maximum daily load implementation and other management practices to target
      specific fecal pollution sources.

PMID- 30192525
TI  - Chemical Derivatization Strategy for Extending the Identification of MHC Class I
      Immunopeptides.
AB  - Neoantigen-based therapeutic vaccines have a high potential impact on tumor
      eradication and patient survival. Mass spectrometry (MS)-based immunopeptidomics
      has the capacity to identify tumor-associated epitopes and pinpoint mutation
      bearing major histocompatibility complex (MHC)-binding peptides. This approach
      presents several challenges, including the identification of low-abundance
      peptides. In addition, MHC peptides have much lower MS/MS identification rates
      than tryptic peptides due to their shorter sequence and lack of basic amino acid
      at C-termini. In this study, we report the development and application of a novel
      chemical derivatization strategy that combines the analysis of native,
      dimethylated, and alkylamidated peptides by liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) to expand the coverage of the MHC peptidome. The results
      revealed that dimethylation increases hydrophobicity and ionization efficiency of
      MHC class I peptides, while alkylamidation significantly improves the
      fragmentation by producing more y-ions during MS/MS fragmentation. Thus, the
      combination of dimethylation and alkylamidation enabled the identification of
      peptides that could not be identified from the analysis of their native form.
      Using this strategy, we identified 3148 unique MHC I peptides from HCT 116 cell
      lines, compared to only 1388 peptides identified in their native form. Among
      these, 10 mutation-bearing peptides were identified with high confidence,
      indicating that this chemical derivatization strategy is a promising approach for
      neoantigen discovery in clinical applications.

PMID- 30192526
TI  - C-H Hydroxylation in Paralytic Shellfish Toxin Biosynthesis.
AB  - The remarkable degree of synthetic selectivity found in Nature is exemplified by
      the biosynthesis of paralytic shellfish toxins such as saxitoxin. The polycyclic
      core shared by saxitoxin and its relatives is assembled and subsequently
      elaborated through the installation of hydroxyl groups with exquisite precision
      that is not possible to replicate with traditional synthetic methods. Here, we
      report the identification of the enzymes that carry out a subset of C-H
      functionalizations involved in paralytic shellfish toxin biosynthesis. We have
      shown that three Rieske oxygenases mediate hydroxylation reactions with perfect
      site- and stereoselectivity. Specifically, the Rieske oxygenase SxtT is
      responsible for selective hydroxylation of a tricyclic precursor to the famous
      natural product saxitoxin, and a second Rieske oxygenase, GxtA, selectively
      hydroxylates saxitoxin to access the oxidation pattern present in gonyautoxin
      natural products. Unexpectedly, a third Rieske oxygenase, SxtH, does not
      hydroxylate tricyclic intermediates, but rather a linear substrate prior to
      tricycle formation, rewriting the biosynthetic route to paralytic shellfish
      toxins. Characterization of SxtT, SxtH, and GxtA is the first demonstration of
      enzymes carrying out C-H hydroxylation reactions in paralytic shellfish toxin
      biosynthesis. Additionally, the reactions of these oxygenases with a suite of
      saxitoxin-related molecules are reported, highlighting the substrate promiscuity
      of these catalysts and the potential for their application in the synthesis of
      natural and unnatural saxitoxin congeners.

PMID- 30192527
TI  - A Review on Energy, Environmental, and Sustainability Implications of Connected
      and Automated Vehicles.
AB  - Connected and automated vehicles (CAVs) are poised to reshape transportation and
      mobility by replacing humans as the driver and service provider. While the
      primary stated motivation for vehicle automation is to improve safety and
      convenience of road mobility, this transformation also provides a valuable
      opportunity to improve vehicle energy efficiency and reduce emissions in the
      transportation sector. Progress in vehicle efficiency and functionality, however,
      does not necessarily translate to net positive environmental outcomes. Here, we
      examine the interactions between CAV technology and the environment at four
      levels of increasing complexity: vehicle, transportation system, urban system,
      and society. We find that environmental impacts come from CAV-facilitated
      transformations at all four levels, rather than from CAV technology directly. We
      anticipate net positive environmental impacts at the vehicle, transportation
      system, and urban system levels, but expect greater vehicle utilization and
      shifts in travel patterns at the society level to offset some of these benefits.
      Focusing on the vehicle-level improvements associated with CAV technology is
      likely to yield excessively optimistic estimates of environmental benefits.
      Future research and policy efforts should strive to clarify the extent and
      possible synergetic effects from a systems level to envisage and address concerns
      regarding the short- and long-term sustainable adoption of CAV technology.

PMID- 30192528
TI  - Nanoplastic Ingestion Enhances Toxicity of Persistent Organic Pollutants (POPs)
      in the Monogonont Rotifer Brachionus koreanus via Multixenobiotic Resistance
      (MXR) Disruption.
AB  - Among the various materials found inside microplastic pollution, nanosized
      microplastics are of particular concern due to difficulties in quantification and
      detection; moreover, they are predicted to be abundant in aquatic environments
      with stronger toxicity than microsized microplastics. Here, we demonstrated a
      stronger accumulation of nanosized microbeads in the marine rotifer Brachionus
      koreanus compared to microsized ones, which was associated with oxidative stress
      induced damages on lipid membranes. In addition, multixenobiotic resistance
      conferred by P-glycoproteins and multidrug resistance proteins, as a first line
      of membrane defense, was inhibited by nanoplastic pre-exposure, leading to
      enhanced toxicity of 2,2',4,4'-tetrabromodiphenyl ether and triclosan in B.
      koreanus. Our study provides a molecular mechanistic insight into the toxicity of
      nanosized microplastics toward aquatic invertebrates and further implies the
      significance of synergetic effects of microplastics with other environmental
      persistent organic pollutants.

PMID- 30192529
TI  - Au(III) and Pt(II) Complexes of a Novel and Versatile 1,4-Disubstituted 1,2,3
      Triazole-Based Ligand Possessing Diverse Secondary and Tertiary Coordinating
      Groups.
AB  - A novel 1,4-disubstituted 1,2,3-triazole-based ligand, 2-(4-(pyridin-2-yl)-1 H
      1,2,3-triazol-1-yl)propane-1,3-diamine (ptpd), which possesses pyridyl and
      diamino secondary and tertiary coordinating groups was synthesized in excellent
      yield. The reactivity of 2-(1-phenyl-1 H-1,2,3-triazol-4-yl)pyridine (ptp), di-
      tert-butyl (2-azidopropane-1,3-diyl)dicarbamate (Boc2-ptpd), and ptpd.3HCl was
      investigated with Au(III) and Pt(II) precursors. Analysis including X-ray crystal
      structures of [Au(III)Cl3(ptp)] (1),
      [Au(III)Cl2(ptpd)][Au(I)Cl2][OH]{[NaAuCl4.2H2O]} n (3), and
      [Pt(II)Cl2(ptpdH2)][PtCl4] (4) revealed that ptpd (i) serves as a monodentate
      ligand for Au(III) coordinating to the metal center via the pyridine nitrogen
      only, (ii) preferentially coordinates Au(III) via the bidentate diamino group
      over the monodentate pyridine group, (iii) can coordinate Pt(II) in a bidentate
      fashion via the pyridyl nitrogen and the triazole N-3, and (iv) can bridge two
      Pt(II) centers through bidentate chelation at the diamino group and bidentate
      chelation via the pyridyl nitrogen and the triazole N-3. ptpd represents a
      versatile ligand template for the development of mixed metal complexes.

PMID- 30192530
TI  - Enzyme-like Click Catalysis by a Copper-Containing Single-Chain Nanoparticle.
AB  - A major challenge in performing reactions in biological systems is the
      requirement for low substrate concentrations, often in the micromolar range. We
      report that copper cross-linked single-chain nanoparticles (SCNPs) are able to
      significantly increase the efficiency of copper(I)-catalyzed alkyne-azide
      cycloaddition (CuAAC) reactions at low substrate concentration in aqueous buffer
      by promoting substrate binding. Using a fluorogenic click reaction and dye uptake
      experiments, a structure-activity study is performed with SCNPs of different size
      and copper content and substrates of varying charge and hydrophobicity. The high
      catalytic efficiency and selectivity are attributed to a mechanism that involves
      an enzyme-like substrate binding process. Saturation-transfer difference (STD)
      NMR spectroscopy, 2D-NOESY NMR, kinetic analyses with varying substrate
      concentrations, and computational simulations are consistent with a Michaelis
      Menten, two-substrate, random-sequential enzyme-like kinetic profile. This
      general approach may prove useful for developing more-sustainable catalysts and
      agents for biomedicine and chemical biology.

PMID- 30192532
TI  - Intermolecular Radical Mediated Anti-Markovnikov Alkene Hydroamination Using N
      Hydroxyphthalimide.
AB  - An intermolecular anti-Markovnikov hydroamination of alkenes has been developed
      using triethyl phosphite and N-hydroxyphthalimide. The process tolerates a wide
      range of alkenes, including vinyl ethers, silanes, and sulfides as well as
      electronically unbiased terminal and internal alkenes. The resultant N
      alkylphthalimides can readily be transformed to the corresponding primary amines.
      Mechanistic probes indicate that the process is mediated via a phosphite promoted
      radical deoxygenation of N-hydroxyphthalimide to access phthalimidyl radicals.

PMID- 30192531
TI  - Characterization of Daily Dietary Intake and the Health Risk of Neonicotinoid
      Insecticides for the U.S. Population.
AB  - Although neonicotinoids have been the most commonly used insecticides globally,
      very limited data related to their dietary intake and health risks are available.
      In this study, we used the relative potency factor approach to aggregate
      individual neonicotinoids into a single metric (IMIRPF) representing the intakes
      of total neonicotinoids in relation to imidacloprid for each food item. We then
      estimated the average daily intake (ADI) of neonicotinoids using residue data
      collected from U.S. Congressional Cafeteria study (USCC) and USDA/PDP and food
      consumption data from NHANES 2011-2012. Among the USCC and USDA/PDP samples,
      squash (427.2 ng/g) and spinach (569.2 ng/g), had the highest average IMIRPF,
      respectively. The estimated ADIs were below the current chronic reference dose
      (cRfD) for imidacloprid. However, due to their wide use, it is logical to expect
      the ubiquity of neonicotinoids in foods. Therefore, the importance of conducting
      routine dietary intake assessment for neonicotinoids should not be ignored.

PMID- 30192533
TI  - Simultaneous Exfoliation and Functionalization of 2H-MoS2 by Thiolated
      Surfactants: Applications in Enhanced Antibacterial Activity.
AB  - Two-dimensional transition metal dichalcogenides (TMDs), such as MoS2, generally
      exist in two different polymorphic structures, metallic (1T phase) and
      semiconducting (2H phase). In context of their wide spectrum of applications
      ranging from electronic to biomedicine, the aspects of ligand conjugation and
      solution processability are highly significant. In addition, the assessment of
      their antibacterial property and biocompatibility is equally important to explore
      their biomedical applications. Here we report a new method for the exfoliation
      and direct functionalization of 2H-MoS2 using surfactant molecules with thiol
      functionality. We found that the exfoliated MoS2 using thiolated ligands are
      functionalized with desired functionality and the processing scheme can be
      extended to other TMDs. Functionalized 2H-MoS2 exhibits highly enhanced
      antibacterial efficiency compared to similarly functionalized metallic 1T-MoS2
      against pathogenic bacteria. The newly synthesized functionalized 2H-MoS2
      exhibits better hemocompatibility, which makes it suitable for in vivo
      applications. This convenient functionalization method opens the door for many
      other applications of functionalized semiconducting 2H-MoS2 and other TMDs.

PMID- 30192534
TI  - Continuum Microkinetic Rate Theory of Lattice Systems: Formalization, Current
      Limitations, and a Possible Basis for Continuum Rate Theory.
AB  - A broad class of reaction networks are controlled not by any thermodynamic
      ensemble but by rates and are referred to as "kinetically constrained". Here,
      microkinetic rate theory is extended into a model of arbitrarily complex reaction
      networks. This microkinetic rate theory takes a form where the constraints
      imposed by kinetically constrained systems apply naturally. This model is
      compared to numerically complete results and is shown to be quantitatively
      predictive. Model deviations are shown to emerge for systems with incomplete
      mixing. This model is analytical and may serve as a basis for device and
      continuum scale rate modeling.

PMID- 30192535
TI  - SlERF2 Is Associated with Methyl Jasmonate-Mediated Defense Response against
      Botrytis cinerea in Tomato Fruit.
AB  - Methyl jasmonate (MeJA) and ethylene play important roles in mediating defense
      responses against Botrytis cinerea. Ethylene response factors (ERFs) are the
      final components of ethylene signal transduction; whether SlERF2 participates in
      disease resistance against Botrytis cinerea is unclear. The objective of this
      study was to investigate the role of SlERF2 in MeJA-mediated defense response by
      using both sense and antisense SlERF2 tomato fruit. Our results showed that both
      MeJA treatment and pathogen infection upregulated SlERF2 expression level.
      Overexpression of SlERF2 enhanced tomato fruit resistance against Botrytis
      cinerea. MeJA treatment increased ethylene production, promoted the activities of
      chitinase, beta-1,3-glucanase, phenylalanine ammonia-lyase, and peroxidase, and
      elevated pathogenesis-related protein content and total phenolic content.
      Moreover, the effects of MeJA on disease response were reinforced in sense SlERF2
      tomato fruit, while they were weakened in antisense SlERF2 tomato fruit. These
      results indicated that SlERF2 was involved in MeJA-mediated disease resistance
      against Botrytis cinerea in tomato fruit.

PMID- 30192536
TI  - MEPicides: alpha,beta-Unsaturated Fosmidomycin Analogues as DXR Inhibitors
      against Malaria.
AB  - Severe malaria due to Plasmodium falciparum remains a significant global health
      threat. DXR, the second enzyme in the MEP pathway, plays an important role to
      synthesize building blocks for isoprenoids. This enzyme is a promising drug
      target for malaria due to its essentiality as well as its absence in humans. In
      this study, we designed and synthesized a series of alpha,beta-unsaturated
      analogues of fosmidomycin, a natural product that inhibits DXR in P. falciparum.
      All compounds were evaluated as inhibitors of P. falciparum. The most promising
      compound, 18a, displays on-target, potent inhibition against the growth of P.
      falciparum (IC50 = 13 nM) without significant inhibition of HepG2 cells (IC50 >
      50 MUM). 18a was also tested in a luciferase-based Plasmodium berghei mouse model
      of malaria and showed exceptional in vivo efficacy. Together, the data support
      MEPicide 18a as a novel, potent, and promising drug candidate for the treatment
      of malaria.

PMID- 30192537
TI  - Calothrixamides A and B from the Cultured Cyanobacterium Calothrix sp. UIC 10520.
AB  - Cyanobacteria are a source of chemically diverse metabolites with potential
      medicinal and biotechnological applications. Rapid identification of compounds is
      central to expedite the natural product discovery process. Mass spectrometry has
      been shown to be an important tool for dereplication of complex natural product
      samples. In addition, chromatographic separation and complementary spectroscopic
      analysis (e.g., UV) can enhance the confidence of the dereplication process.
      Here, we applied a droplet-liquid microjunction-surface sampling probe (droplet
      probe) coupled with UPLC-PDA-HRMS-MS/MS to identify two new natural products in
      situ from the freshwater strain Calothrix sp. UIC 10520. This allowed us to
      prioritize this strain for chemical investigation based on the presence of new
      metabolites very early in our discovery process, saving both time and resources.
      Subsequently, calothrixamides A (1) and B (2) were isolated from large-scale
      cultures, and the structures were elucidated by 1D and 2D NMR spectroscopy and
      mass spectrometry. The absolute configurations were determined by a combination
      of chemical degradation reactions, derivatization methods (Mosher's, Marfey's,
      and phenylglycine methyl ester), and J-based configurational analysis.
      Calothrixamides showed no cytotoxic activity against the MDA-MB-435, MDA-MB-231,
      and OVCAR3 cancer cell lines. They represent the first functionalized long-chain
      fatty acid amides reported from the Calothrix genus and from a freshwater
      cyanobacterium.

PMID- 30192538
TI  - On the Stability of Proteins Solvated in Imidazolium-Based Ionic Liquids Studied
      with Replica Exchange Molecular Dynamics.
AB  - The stability of two small proteins, one composed of three alpha-helices (alpha
      peptide) and another composed of a beta-sheet (beta-peptide) solvated in five
      different ionic liquids (ILs), is analyzed using replica exchange molecular
      dynamics (REMD) simulations. ILs are composed of 1-butyl-3-methylimidazolium
      (BMIM) cations, paired with five different anions of varying hydrophilicity and
      size, namely, Cl-, NO3-, BF4-, PF6-, and NTf2-. REMD simulations greatly improve
      structure sampling and mitigate bias toward the initial folded peptide structure,
      thereby providing more adequate simulations to study protein stability. Cluster
      analysis, DSSP analysis and derivation of radius of gyration, interaction
      energies, and hydrogen bonding are used to quantify structural peptide changes in
      a large temperature range from 250 to 650 K. alpha-Peptides are least stable in
      ILs that contain small anions with localized negative charge, such as in BMIM-Cl
      and BMIM-NO3. Destabilization is caused by direct electrostatic interactions of
      anions with alpha-helices that are exposed to the solvent. This destabilization
      is characterized not by unfolded but instead by compact misfolded structures.
      Also, beta-peptides retain compact structures up to at least 400 K, below which
      unfolding hardly occurs. However, intrapeptide hydrogen bonds that constitute the
      beta-sheet are not exposed to the solvent. Therefore, beta-peptides are generally
      more stable than alpha-peptides in all considered ILs. Moreover, on contrary to
      alpha-peptides, beta-peptides are least stable in less polar ILs, such as BMIM
      PF6 and BMIM-NTf2, because dissolving beta-sheets requires large structural
      changes of the peptide. Such transitions are energetically less opposed in ILs
      with weaker mutual ion coordination. A large interaction density within ILs, for
      example, in BMIM-Cl, is thus kinetically trapping beta-peptides in the original
      folded state. Additionally, in BMIM-BF4, interactions with beta-peptides are so
      weak, compared to an aqueous solvent, resulting in stronger interactions within
      the peptide, which extend beta-sheets, hence causing misfolding of a different
      kind. The results reveal how direct ion-peptide interactions and solvent
      reorganization energy in ILs are both crucial in determining protein stability.
      These insights could translate into guidelines for the design of new IL solvents
      with improved protein stability.

PMID- 30192539
TI  - Identification of Ethylene Responsive miRNAs and Their Targets from Newly
      Harvested Banana Fruits Using High-Throughput Sequencing.
AB  - The roles of microRNAs (miRNAs) related to ethylene response in banana fruits
      remain unknown because many miRNAs are differentially expressed as the fruit
      ripens, making the identification of ethylene-responsive miRNAs difficult. Using
      newly harvested banana fruits (within 5 h after harvest) as material, we found
      that these fruit did not ripen when treated with 5 MUL/L of ethylene for 12 h at
      22  degrees C. Two miRNA libraries were generated from newly harvested banana
      fruits with and without ethylene treatment and sequenced. In total, 128 known
      miRNAs belonging to 42 miRNA families were obtained, and 12 novel miRNAs were
      identified. Among them, 22 were differentially expressed in response to ethylene
      treatment, among which 6 known miRNAs and their putative targets were validated
      using qRT-PCR. These putative targets encoded proteins including GATA, ARF, DLC,
      and AGO, etc. KEGG and GO analyses showed that miRNAs differentially expressed in
      response to ethylene mainly function in the molecular and biological processes.

PMID- 30192540
TI  - Tetrahydro-4 H-(pyrrolo[3,4- d]isoxazol-3-yl)methanamine: A Bicyclic Diamino
      Scaffold Stabilizing Parallel Turn Conformations.
AB  - A tetrahydro-4 H-(pyrrolo[3,4- d]isoxazol-3-yl)methanamine scaffold was designed
      as a diamino derivative to stabilize parallel turn conformations. Its synthesis
      took advantage of a [1,3]-dipolar cycloaddition reaction between the nitrile
      oxide derived from the inexpensive enantiopure l -phenylalanine and N-benzyl-3
      pyrroline. Two diastereoisomers were formed, whose distribution depends on the
      selected base. 3a R,6a S-Isomer is favored in organic bases, which formation is
      driven by pi-interactions. However, the above interactions were significantly
      prevented using an inorganic base due to the chaotropic effect of the cation,
      decreasing the amount of the above isomer. Finally, we demonstrated that this
      isomer is able to stabilize parallel turn conformations when inserted in short
      peptide sequences.

PMID- 30192541
TI  - A Dual-App Nucleoside Probe Provides Structural Insights into the Human Telomeric
      Overhang in Live Cells.
AB  - Understanding the topology adopted by individual G-quadruplex (GQ)-forming
      sequences in vivo and targeting a specific GQ motif among others in the genome
      will have a profound impact on GQ-directed therapeutic strategies. However, this
      remains a major challenge as most of the tools poorly distinguish different GQ
      conformations and are not suitable for both cell-free and in-cell analysis. Here,
      we describe an innovative probe design to investigate GQ conformations and
      recognition in both cell-free and native cellular environments by using a
      conformation-sensitive dual-app nucleoside analogue probe. The nucleoside probe,
      derived by conjugating fluorobenzofuran at the 5-position of 2'-deoxyuridine, is
      composed of a microenvironment-sensitive fluorophore and an in-cell NMR
      compatible 19F label. This noninvasive nucleoside, incorporated into the human
      telomeric DNA oligonucleotide repeat, serves as a common probe to distinguish
      different GQ topologies and quantify topology-specific binding of ligands by
      fluorescence and NMR techniques. Importantly, unique signatures displayed by the
      19F-labeled nucleoside for different GQs enabled a systematic study in Xenopus
      laevis oocytes to provide new structural insights into the GQ topologies adopted
      by human telomeric overhang in cells, which so far has remained unclear. Studies
      using synthetic cell models, immunostaining on fixed cells, and crystallization
      conditions suggest that parallel GQ is the preferred conformation of telomeric
      DNA repeat. However, our findings using the dual-app probe clearly indicate that
      multiple structures including hybrid-type parallel-antiparallel and parallel GQs
      are formed in the cellular environment. Taken together, our findings open new
      experimental strategies to investigate topology, recognition, and therapeutic
      potential of individual GQ-forming motifs in a biologically relevant context.

PMID- 30192542
TI  - Intramolecular Torque Study of a Molecular Rotation Stimulated by Electron
      Injection and Extraction.
AB  - Rotation-inducing torque based on interatomic forces is a true indicator of
      internal molecular rotations. We use the induced intramolecular torque to study
      the underlying rotational mechanism stimulated by an electron injection or
      extraction for the rotor molecule 9-(2,4,7-trimethyl-2,3-dihydro-1 H-inden-1
      ylidene)-9 H-fluorene, which consists of a "rotator" fragment and a "stator"
      fragment. The results show that the charged molecule in a quartet spin state can
      rotate internally, while that in the doublet state cannot. The torque on the
      rotator in the quartet state always maintains unidirectional rotation. In
      addition, the attachment/extraction of an electron leads to the reduction of the
      rotational energy barrier by about 18 kcal/mol, facilitating a more favorable
      molecular rotation than in the neutral singlet state. Our finding provides a
      molecular-level understanding of various transformation pathways for experimental
      designs and further demonstrates the effectiveness of the torque approach.

PMID- 30192543
TI  - Electronic Energies Are Not Enough: An Ion Mobility-Aided, Quantum Chemical
      Benchmark Analysis of H+GPGG Conformers.
AB  - Peptides and proteins exist not as single, lowest energy structures but as
      ensembles of states separated by small barriers. In order to study these species
      we must be able to correctly identify their gas phase conformational
      distributions, and ion mobility spectrometry (IMS) has arisen as an experimental
      method for assessing the gas phase energetics of flexible peptides. Here, we
      present a thorough exploration and benchmarking of the low energy conformers of
      the small, hairpin peptide H+GPGG with the aid of ion mobility spectrometry
      against a wide swath of density functionals (35 dispersion-corrected and
      uncorrected functionals represented by 21 unique exchange-correlation
      functionals) and wave function theory methods (15 total levels of theory). The
      three experimentally resolved IMS peaks were found to correspond to three
      distinct pairs of conformers, each pair composed of species differing only by the
      chair or boat configuration of the proline. Two of the H+GPGG conformer pairs
      possess a cis configuration about the Pro-Gly1 peptide bond while the other
      adopts a trans configuration. While the experimental spectrum reports a higher
      intensity for the cis-1 conformer than the trans conformer, 13 WFT levels of
      theory, including a complete basis set CCSD(T) extrapolation, obtain trans to be
      favored in terms of the electronic energy. This same effect is seen in 14 of the
      18 dispersion-corrected density functionals studied, whereas the remaining 17
      functionals show more variety. Only when Gibbs free energies are considered do
      the WFT methods and dispersion-corrected functionals reflect the experimental
      distribution. CAM-B3LYP-D3BJ emerges as the best-performing density functional,
      matching the experimental distribution and the CCSD(T)/CBS relative energies
      within 6%. Further analysis reveals the trans conformer to be favored
      electronically, but entropically disfavored, leading to the experimental
      preference of the cis-1 conformer. These results highlight the danger in
      considering only the electronic energies, which is common practice in electronic
      structure theory predictions of conformational energy distributions.
      Additionally, the effects of temperature and scaling of the frequencies used in
      obtaining the Gibbs free energies are explored.

PMID- 30192544
TI  - De Novo Design of alpha-Helical Lipopeptides Targeting Viral Fusion Proteins: A
      Promising Strategy for Relatively Broad-Spectrum Antiviral Drug Discovery.
AB  - Class I enveloped viruses share similarities in their apparent use of a hexameric
      coiled-coil assembly to drive the merging of virus and host cell membranes.
      Inhibition of coiled coil-mediated interactions using bioactive peptides that
      replicate an alpha-helical chain from the viral fusion machinery has significant
      antiviral potential. Here, we present the construction of a series of
      lipopeptides composed of a de novo heptad repeat sequence-based alpha-helical
      peptide plus a hydrocarbon tail. Promisingly, the constructs adopted stable alpha
      helical conformations and exhibited relatively broad-spectrum antiviral
      activities against Middle East respiratory syndrome coronavirus (MERS-CoV) and
      influenza A viruses (IAVs). Together, these findings reveal a new strategy for
      relatively broad-spectrum antiviral drug discovery by relying on the tunability
      of the alpha-helical coiled-coil domains present in all class I fusion proteins
      and the amphiphilic nature of the individual helices from this multihelix motif.

PMID- 30192546
TI  - Pd(II)-Catalyzed [4 + 2] Heterocyclization Sequence for Polyheterocycle
      Generation.
AB  - A new Pd(II)-catalyzed cascade sequence for the formation of polyheterocycles,
      from simple starting materials, is reported. The sequence is applicable to both
      indole and pyrrole substrates, and a range of substituents are tolerated. The
      reaction is thought to proceed by a Pd(II)-catalyzed C-H activated Heck reaction
      followed by a second Pd(II)-catalyzed aza-Wacker reaction with two Cu(II)
      mediated Pd(0) turnovers per sequence. The sequence can be considered a formal [4
      + 2] heterocyclization.

PMID- 30192545
TI  - Comparison of an Optimized Ultracentrifugation Method versus Size-Exclusion
      Chromatography for Isolation of Exosomes from Human Serum.
AB  - Exosomes are nanosized vesicles that are abundant in biological fluids. In recent
      years, exosomes have attracted increasing attention as their cargo may provide
      promising biomarkers for the early diagnosis of and therapy for many diseases,
      such as cancer. In addition to ultracentrifugation (UC), many alternative methods
      including size-exclusion chromatography (SEC) have been developed for isolating
      exosomes. It has been reported that the SEC method provided improved performance
      relative to the UC method in isolating exosomes from plasma, where the former
      contained less residual blood protein contamination. We have compared the SEC
      method with an optimized UC method in isolating exosomes from human serum. This
      was based on dilution of the serum to reduce the viscosity and a prolonged cycle
      of UC, followed by another four cycles. We found that >95% of serum proteins were
      removed without a significant loss of exosome proteins relative to SEC. We also
      combined one cycle of UC with SEC and found that this method provided improved
      results relative to the SEC method, although the serum protein contamination was
      several times higher than that of our optimized UC method. The TEM showed that
      the size distribution of exosomes isolated from each of the three methods was
      similar.

PMID- 30192547
TI  - Exceptional Antisintering Gold Nanocatalyst for Diesel Exhaust Oxidation.
AB  - The poor thermodynamic stability of gold nanoparticles (NPs) makes it very
      challenging to stabilize them in small sizes at elevated temperatures. Herein, we
      report the preparation of antisintering Au nanocatalyst by rationally selecting
      the sublattice matched MgGa2O4 spinel as support based on theoretical
      predictions. Au/MgGa2O4 retains Au NPs of 2-5 nm even after aging over the
      melting temperature of bulk gold (1064  degrees C)! By identifying the stable
      structure, the extraordinary stability is found to arise from the formation of a
      new phase structure, namely Au-MgGa2O4 metal-oxide "hetero-bicrystal" that
      remains as crystallite without melting even at 1100  degrees C. More than 80% of
      the loaded Au can be efficiently stabilized so that the catalysts can exhibit
      excellent low-temperature activities for diesel exhaust (CO and C3H6) oxidation
      after severely thermal and hydrothermal aging. These results may pave ways for
      constructing antisintering gold nanocatalysts for industrial applications.

PMID- 30192548
TI  - Innovative DNA-Targeted Metallo-prodrug Strategy Combining Histone Deacetylase
      Inhibition with Oxidative Stress.
AB  - Cancer remains a global health challenge. There is an urgent need to develop
      innovative therapeutics that can overcome the shortcomings of existing cancer
      therapies. DNA enzymes involved in nucleic acid compaction and organization are
      an attractive cancer drug target for therapeutic exploitation. In this work, a
      family of Cu(II) prodrugs containing suberoylanilide hydroxamic acid (SAHA), a
      well-established histone deacetylase inhibitor (HDACi) and clinically approved
      cancer drug, and phenanthrene ligands as DNA intercalative components have been
      rationally developed. The complexes, of general formula [Cu(SAHA-1H)( N, N'
      phenanthrene)]+, exhibit excellent DNA recognition with binding affinity of lead
      agents in the order of ~107 M(bp)-1. Biophysical studies involving nucleic acid
      polymers indicate intercalative binding at both adenine-thymine (A-T) and guanine
      cytosine (G-C) rich sequences but thermodynamically stable interactions are
      favored in G-C tracts. The complexes mediate DNA damage by producing reactive
      oxygen species (ROS) with spin trapping experiments showing that superoxide, the
      hydroxyl radical, and hydrogen peroxide play critical roles in strand scission.
      The agents were found to have promising antiproliferative effects against a panel
      of epithelial cancers, and in two representative cell lines possessing mutated
      p53 (SK-OV-3 and DU145), enhanced cytotoxicity was observed. Significantly,
      mechanistic experiments with the most promising candidates revealed HDAC
      inhibition activity was achieved over a shorter time frame as compared to
      clinical standards with DNA damage-response markers identifying upregulation of
      both DNA synthesis and nucleotide excision repair (NER) pathways. Finally,
      confocal imaging and gene expression analysis show this metallodrug class exerts
      cytotoxic activity predominantly through an apoptotic pathway.

PMID- 30192550
TI  - Cross-Dehydrogenating Coupling of Aldehydes with Amines/R-OTBS Ethers by Visible
      Light Photoredox Catalysis: Synthesis of Amides, Esters, and Ureas.
AB  - A straightforward synthesis of amides, ureas, and esters is reported by visible
      light cross-dehydrogenating coupling (CDC) of aldehydes (or amine carbaldehydes)
      and amines/R-OTBS ethers by photoredox catalysis. The reaction is found to be
      general and high yielding. A plausible mechanistic pathway has been proposed for
      these transformations and is supported by appropriate controlled experiments.

PMID- 30192549
TI  - Cholesterol Flip-Flop Impacts Domain Registration in Plasma Membrane Models.
AB  - The plasma membrane is a highly complex multicomponent system that is central to
      the functioning of cells. Cholesterol, a key lipid component of the plasma
      membrane, promotes the formation of nanodomains. These nanodomains are often
      correlated across the two membrane leaflets, but the underlying physical
      mechanism remains unclear. Using coarse-grained molecular dynamics simulations,
      we investigate the influence of cholesterol flip-flop on membrane properties, in
      particular, the interleaflet coupling of cholesterol-enriched domains. We show
      that the cholesterol density correlation between the leaflets of an average
      mammalian plasma membrane is significantly reduced by suppressing interleaflet
      cholesterol population. Our results suggest an amplifying role of cholesterol in
      signal transduction across the leaflets.

PMID- 30192551
TI  - SILAC-MS Profiling of Reconstituted Human Chromatin Platforms for the Study of
      Transcription and RNA Regulation.
AB  - DNA packaged into chromatin is the core structure of the human genome. Nearly all
      eukaryotic genome regulation must interface with this genomic structure, and
      modification of the chromatin can influence molecular mechanisms that regulate
      the underlying DNA. Many processes are governed by regulated stepwise assembly
      mechanisms that build complex machinery on chromatin to license a specific
      activity such as transcription. Transcriptional activators drive the initial
      steps of gene expression, regulated in part by chromatin. Here we describe tools
      to study the stepwise assembly of protein complexes on chromatin in a highly
      controlled manner using reconstituted human chromatin platforms and quantitative
      proteomic profiling. We profile the early steps in transcriptional activation and
      highlight the potential for understanding the multiple ways chromatin can
      influence transcriptional regulation. We also describe modifications of this
      approach to study the activity of a long noncoding RNA to act as a dynamic
      scaffold for proteins to be recruited to chromatin. This approach has the
      potential to provide a more comprehensive understanding of important
      macromolecular complex assembly that occurs on the human genome. The
      reconstituted nature of the chromatin substrate offers a tunable system that can
      be trapped at specific substeps to understand how chromatin interfaces with
      genome regulation machinery.

PMID- 30192552
TI  - Oxidative Cross-Coupling of Boron and Antimony Nucleophiles via Palladium(I).
AB  - The use of an isolatable, monomeric Pd(I) complex as a catalyst for the oxidative
      cross-coupling of aryl-antimony and aryl-boron nucleophiles is reported. This
      reaction tolerates a wide variety of substrates, with >20:1 selectivity for cross
      coupled products. This strategy offers a new approach to achieving the selective
      cross-coupling of nucleophiles.

PMID- 30192553
TI  - Electronic Excited States from the Adiabatic-Connection Formalism with Complete
      Active Space Wave Functions.
AB  - It is demonstrated how the recently proposed multireference adiabatic-connection
      (AC) approximation for electron correlation energy ( Pernal , K. Electron
      Correlation from the Adiabatic Connection for Multireference Wave Functions .
      Phys. Rev. Lett. 2018 , 120 , 013001 ) can be extended to predicting correlation
      energy in excited states of molecules. It is the first successful application of
      the AC approach to computing excited-states energies of molecules using a
      complete active space (CAS) wave function as a reference. The unique feature of
      the AC-CAS approach with respect to popular methods such as CASPT2 and NEVPT2 is
      that it requires only one- and two-particle reduced density matrices, making it
      possible to efficiently treat large spaces of active electrons. Application of
      the simpler variant of AC, the AC0, which is based on the first-order expansion
      of the AC integrand at the uncorrelated system limit, to excited states yields
      excitation energies with accuracy rivaling that of the NEVPT2 method but at
      greatly reduced computational cost.

PMID- 30192554
TI  - Synthetic Study toward the Total Synthesis of Taxezopidines A and B.
AB  - A concise synthetic approach to construct the [6,8,6]-tricyclic core of
      taxezopidines A and B, which contains a synthetically challenging bridged
      bicyclo[5.3.1]undecane ring system bearing most of the desired functionalized
      groups and stereocenters, has been established. This approach features a
      diastereoselective type II intramolecular Diels-Alder furan reaction. The
      stereochemistry of the acetoxy group at the allylic position of the dienophile
      alkene group, such as in 6a, was found to be critical for achieving the desired
      highly diastereoselective outcome.

PMID- 30192555
TI  - Computationally Assisted Assignment of the Kadsuraols, a Class of Chemopreventive
      Agents for the Control of Liver Cancer.
AB  - Kadsuraols A-C (1-3), which are tetrahydrocyclobutaphenanthrofuranone-type
      lignans with a new carbon skeleton comprising a four-membered ring across C-1'-C
      8, have been isolated from the roots of Kadsura longipedunculata. Their
      structures and absolute configurations were unambiguously determined using
      nuclear magnetic resonance, X-ray diffraction crystallography, DP4+ calculations,
      and computed and experimental electronic circular dichroism spectra. Kadsuraol C
      (3) exhibited hepatoprotective activity against N-acetyl- p-aminophenol (APAP)
      induced toxicity. The compounds showed no cytotoxicity at 10 MUM in a zone assay.

PMID- 30192556
TI  - Iridium-Catalyzed Reductive Nucleophilic Addition to Secondary Amides.
AB  - An iridium-catalyzed reductive nucleophilic addition to secondary amides is
      reported. After the iridium-catalyzed reduction, the resulting imines can undergo
      the Strecker reaction, the Mannich reaction, allylation, and [3 + 2]
      cycloaddition. The method shows high chemoselectivity in the presence of other
      functional groups such as methyl ester.

PMID- 30192557
TI  - Asymmetric Rh(I)-Catalyzed Functionalization of the 3-C( sp3)-H Bond of
      Benzofuranones with alpha-Diazoesters.
AB  - An asymmetric Rh(I)-catalyzed functionalization of the 3-C( sp3)-H bond of
      benzofuranones with alpha-diazoesters has been developed, providing a new
      strategy for the stereoselective 3-alkylation of benzofuranones. With low
      catalyst loadings (low to 0.02 mol % Rh), a number of benzofuranones bearing
      consecutive quaternary and tertiary stereogenic centers have been synthesized (up
      to 94% yield, 95:5 dr, and >99% ee). The synthetic utilities of this methodology
      have been demonstrated by elaborating the model product 3aa to a series of
      enantiopure compounds with similarities to natural products and drug candidates.

PMID- 30192559
TI  - Water-Activated VOPO4 for Magnesium Ion Batteries.
AB  - Rechargeable Mg batteries, using high capacity and dendrite-free Mg metal anodes,
      are promising energy storage devices for large scale smart grid due to low cost
      and high safety. However, the performance of Mg batteries is still plagued by the
      slow reaction kinetics of their cathode materials. Recent discoveries demonstrate
      that water in cathode can significantly enhance the Mg-ion diffusion in cathode
      by an unknown mechanism. Here, we propose the water-activated layered-structure
      VOPO4 as a novel cathode material and examine the impact of water in electrode or
      organic electrolyte on the thermodynamics and kinetics of Mg-ion
      intercalation/deintercalation in cathodes. Electrochemical measurements verify
      that water in both VOPO4 lattice and organic electrolyte can largely activate
      VOPO4 cathode. Thermodynamic analysis demonstrates that the water in the
      electrolyte will equilibrate with the structural water in VOPO4 lattice, and the
      water activity in the electrolyte alerts the mechanism and kinetics for
      electrochemical Mg-ion intercalation in VOPO4. Theoretical calculations and
      experimental results demonstrate that water reduces both the solid-state
      diffusion barrier in the VOPO4 electrode and the desolvation penalty at the
      interface. To achieve fast reaction kinetics, the water activity in the
      electrolyte should be larger than 10-2. The proposed activation mechanism
      provides guidance for screening and designing novel chemistry for high
      performance multivalent-ion batteries.

PMID- 30192558
TI  - Molecular-Beam Epitaxy of Two-Dimensional In2Se3 and Its Giant Electroresistance
      Switching in Ferroresistive Memory Junction.
AB  - Ferroelectric thin film has attracted great interest for nonvolatile memory
      applications and can be used in either ferroelectric Schottky diodes or
      ferroelectric tunneling junctions due to its promise of fast switching speed,
      high on-to-off ratio, and nondestructive readout. Two-dimensional alpha-phase
      indium selenide (In2Se3), which has a modest band gap and robust ferroelectric
      properties stabilized by dipole locking, is an excellent candidate for
      multidirectional piezoelectric and switchable photodiode applications. However,
      the large-scale synthesis of this material is still elusive, and its performance
      as a ferroresistive memory junction is rarely reported. Here, we report the low
      temperature molecular-beam epitaxy (MBE) of large-area monolayer alpha-In2Se3 on
      graphene and demonstrate the use of alpha-In2Se3 on graphene in ferroelectric
      Schottky diode junctions by employing high-work-function gold as the top
      electrode. The polarization-modulated Schottky barrier formed at the interface
      exhibits a giant electroresistance ratio of 3.9 * 106 with a readout current
      density of >12 A/cm2, which is more than 200% higher than the state-of-the-art
      technology. Our MBE growth method allows a high-quality ultrathin film of In2Se3
      to be heteroepitaxially grown on graphene, thereby simplifying the fabrication of
      high-performance 2D ferroelectric junctions for ferroresistive memory
      applications.

PMID- 30192560
TI  - Combining Organocatalysis and Iodine Catalysis: One-Pot Sequential Catalytic
      Synthesis of Chiral Spirodihydrobenzofuran Pyrazolones and Spirodihydrobenzofuran
      Oxindoles.
AB  - A new and efficient catalytic strategy that combines asymmetric organocatalysis
      and iodine catalysis was first developed for the one-pot Michael/iodization/SN2
      nucleophilic substitution sequential catalytic synthesis of
      spirodihydrobenzofuran pyrazolones and spirodihydrobenzofuran oxindoles. The
      approach results in products with moderate to high yields (up to 93%), high to
      excellent enantioselectivities (up to 99% ee), and excellent
      diastereoselectivities (up to >99:1 dr). The reaction features simple operation
      and is metal-free and base-free.

PMID- 30192561
TI  - Activity-Based Protein Profiling of Intraoperative Serine Hydrolase Activities
      during Cardiac Surgery.
AB  - The processes involved in the initiation of acute kidney injury (AKI) following
      cardiopulmonary bypass (CPB) are thought to occur during the intraoperative
      period. Such a rapid development might indicate that some of the inductive events
      are not dependent on de novo protein synthesis, raising the possibility that
      changes in activities of pre-existing enzymes could contribute to the development
      of AKI. Activity-based protein profiling (ABPP) was used to compare the serine
      hydrolase enzyme activities present in the urines of CPB patients who
      subsequently developed AKI versus those who did not (non-AKI) during the intra-
      and immediate postoperative periods. Sequential urines collected from a nested
      case-control cohort of AKI and non-AKI patients were reacted with a serine
      hydrolase activity probe, fluorophosphonate-TAMRA, and separated by SDS-PAGE. The
      patterns and levels of probe-labeled proteins in the two groups were initially
      comparable. However, within 1 h of CPB there were significant pattern changes in
      the AKI group. Affinity purification and mass spectrometry-based analysis of
      probe-labeled enzymes in AKI urines at 1 h CPB and arrival to the intensive care
      unit (ICU) identified 28 enzymes. Quantitative analysis of the activity of one of
      the identified enzymes, kallikrein-1, revealed some trends suggesting differences
      in the levels and temporal patterns of enzyme activity between a subset of
      patients who developed AKI and those who did not. A comparative analysis of
      affinity-purified probe reacted urinary proteins from these patient groups during
      the intraoperative period suggested the presence of both shared and unique enzyme
      patterns. These results indicate that there are intraoperative changes in the
      levels and types of serine hydrolase activities in patients who subsequently
      develop AKI. However, the role of these activity differences in the development
      of AKI remains to be determined.

PMID- 30192562
TI  - Magnetic and Structural Quantum Phase Transitions in CeCu_{6-x}Au_{x} are
      Independent.
AB  - The heavy-fermion compound CeCu_{6-x}Au_{x} has become a model system for
      unconventional magnetic quantum criticality. For small Au concentrations
      0<=x<0.16, the compound undergoes a structural transition from orthorhombic to
      monoclinic crystal symmetry at a temperature T_{s} with T_{s}->0 for x~0.15.
      Antiferromagnetic order sets in close to x~0.1. To shed light on the interplay
      between quantum-critical magnetic and structural fluctuations we performed
      neutron-scattering and thermodynamic measurements on samples with 0<=x<=0.3. The
      resulting phase diagram shows that the antiferromagnetic and monoclinic phase
      coexist in a tiny Au concentration range between x~0.1 and 0.15. The application
      of hydrostatic and chemical pressure allows us to clearly separate the
      transitions from each other and to explore a possible effect of the structural
      transition on the magnetic quantum-critical behavior. Our measurements
      demonstrate that at low temperatures the unconventional quantum criticality
      exclusively arises from magnetic fluctuations and is not affected by the
      monoclinic distortion.

PMID- 30192563
TI  - Anharmonic Magnon Excitations in Noncollinear and Charge-Ordered
      RbFe^{2+}Fe^{3+}F_{6}.
AB  - RbFe^{2+}Fe^{3+}F_{6} is an example of a charge ordered antiferromagnet where
      iron sites, with differing valences, are structurally separated into two
      interpenetrating sublattices. The low temperature magnetically ordered Fe^{2+}
      (S=2) and Fe^{3+} (S=5/2) moments form a noncollinear orthogonal structure with
      the Fe^{3+} site displaying a reduced static ordered moment. Neutron spectroscopy
      on single crystals finds two distinct spin wave branches with a dominant coupling
      along the Fe^{3+} chain axis (b axis). High resolution spectroscopic measurements
      find an intense energy and momentum broadened magnetic band of scattering
      bracketing a momentum-energy region where two magnon processes are kinematically
      allowed. These anharmonic excitations are enhanced in this noncollinear magnet
      owing to the orthogonal spin arrangement.

PMID- 30192564
TI  - Curvature as a Guiding Field for Patterns in Thin Block Copolymer Films.
AB  - Experimental data on thin films of cylinder-forming block copolymers (BC)-free
      standing BC membranes as well as supported BC films-strongly suggest that the
      local orientation of the BC patterns is coupled to the geometry in which the
      patterns are embedded. We analyze this phenomenon using general symmetry
      considerations and numerical self-consistent field studies of curved BC films in
      cylindrical geometry. The stability of the films against curvature-induced
      dewetting is also analyzed. In good agreement with experiments, we find that the
      BC cylinders tend to align along the direction of curvature at high curvatures.
      At low curvatures, we identify a transition from perpendicular to parallel
      alignment in supported films, which is absent in free-standing membranes. Hence
      both experiments and theory show that curvature can be used to manipulate and
      align BC patterns.

PMID- 30192565
TI  - Broadband Terahertz Generation via the Interface Inverse Rashba-Edelstein Effect.
AB  - Novel mechanisms for electromagnetic wave emission in the terahertz frequency
      regime emerging at the nanometer scale have recently attracted intense attention
      for the purpose of searching next-generation broadband THz emitters. Here, we
      report broadband THz emission, utilizing the interface inverse Rashba-Edelstein
      effect. By engineering the symmetry of the Ag/Bi Rashba interface, we demonstrate
      a controllable THz radiation (~0.1-5  THz) waveform emitted from metallic
      Fe/Ag/Bi heterostructures following photoexcitation. We further reveal that this
      type of THz radiation can be selectively superimposed on the emission discovered
      recently due to the inverse spin Hall effect, yielding a unique film thickness
      dependent emission pattern. Our results thus offer new opportunities for
      versatile broadband THz radiation using the interface quantum effects.

PMID- 30192566
TI  - Damped Perturbations in the No-Boundary State.
AB  - We evaluate the no-boundary path integral exactly in a Bianchi type IX
      minisuperspace with two scale factors. In this model the no-boundary proposal can
      be implemented by requiring one scale factor to be zero initially together with a
      judiciously chosen regularity condition on the momentum conjugate to the second
      scale factor. Taking into account the nonlinear backreaction of the perturbations
      we recover the predictions of the original semiclassical no-boundary proposal. In
      particular we find that large perturbations are strongly damped, consistent with
      vacuum state wave functions.

PMID- 30192567
TI  - Finite-Temperature Relativistic Nuclear Field Theory: An Application to the
      Dipole Response.
AB  - Nuclear response theory beyond the one-loop approximation is formulated for the
      case of finite temperature. For this purpose, the time blocking approximation to
      the time-dependent part of the in-medium nucleon-nucleon interaction amplitude is
      adopted for the thermal (imaginary-time) Green's function formalism. We found
      that introducing a soft blocking, instead of a sharp blocking at zero
      temperature, brings the Bethe-Salpeter equation to a single-frequency variable
      equation also at finite temperatures. The method is implemented self-consistently
      in the framework of quantum hadrodynamics and designed to connect the high-energy
      scale of heavy mesons and the low-energy domain of nuclear medium polarization
      effects in a parameter-free way. In this framework, we investigate the
      temperature dependence of dipole spectra in the even-even nuclei ^{48}Ca and
      ^{100,120,132}Sn with a special focus on the giant dipole resonance's width
      problem and on the low-energy dipole strength distribution.

PMID- 30192568
TI  - 3D Dirac Plasmons in the Type-II Dirac Semimetal PtTe_{2}.
AB  - Transition-metal dichalcogenides showing type-II Dirac fermions are emerging as
      innovative materials for nanoelectronics. However, their excitation spectrum is
      mostly unexplored yet. By means of high-resolution electron energy loss
      spectroscopy and density functional theory, here, we identify the collective
      excitations of type-II Dirac fermions (3D Dirac plasmons) in PtTe_{2} single
      crystals. The observed plasmon energy in the long-wavelength limit is ~0.5  eV,
      which makes PtTe_{2} suitable for near-infrared optoelectronic applications. We
      also demonstrate that interband transitions between the two Dirac bands in
      PtTe_{2} give rise to additional excitations at ~1 and ~1.4  eV. Our results are
      crucial to bringing to fruition type-II Dirac semimetals in optoelectronics.

PMID- 30192569
TI  - Topological Defects in Anisotropic Driven Open Systems.
AB  - We study the dynamics and unbinding transition of vortices in the compact
      anisotropic Kardar-Parisi-Zhang equation. The combination of nonequilibrium
      conditions and strong spatial anisotropy drastically affects the structure of
      vortices and amplifies their mutual binding forces, thus stabilizing the ordered
      phase. We find novel universal critical behavior in the vortex-unbinding
      crossover in finite-size systems. These results are relevant for a wide variety
      of physical systems, ranging from strongly coupled light-matter quantum systems
      to dissipative time crystals.

PMID- 30192570
TI  - Origins of the Unidirectional Spin Hall Magnetoresistance in Metallic Bilayers.
AB  - Recent studies evidenced the emergence of asymmetric electron transport in
      layered conductors owing to the interplay between electrical conductivity,
      magnetization, and the spin Hall or Rashba-Edelstein effects. Here, we
      investigate the unidirectional magnetoresistance (UMR) caused by the current
      induced spin accumulation in Co/Pt and CoCr/Pt bilayers. We identify three
      competing mechanisms underpinning the resistance asymmetry, namely, interface and
      bulk spin-dependent electron scattering and electron-magnon scattering. Our
      measurements provide a consistent description of the current, magnetic field, and
      temperature dependence of the UMR and show that both positive and negative UMR
      can be obtained by tuning the interface and bulk spin-dependent scattering.

PMID- 30192572
TI  - Inter-Landau-level Andreev Reflection at the Dirac Point in a Graphene Quantum
      Hall State Coupled to a NbSe_{2} Superconductor.
AB  - Superconductivity and the quantum Hall effect are distinct states of matter
      occurring in apparently incompatible physical conditions. Recent theoretical
      developments suggest that the coupling of the quantum Hall effect with a
      superconductor can provide fertile ground for realizing exotic topological
      excitations such as non-Abelian Majorana fermions or Fibonacci particles. As a
      step toward that goal, we report observation of Andreev reflection at the
      junction of a quantum Hall edge state in a single layer graphene and a quasi-two
      dimensional niobium diselenide (NbSe_{2}) superconductor. Our principal finding
      is the observation of an anomalous finite-temperature conductance peak located
      precisely at the Dirac point, providing a definitive evidence for inter-Landau
      level Andreev reflection in a quantum Hall system. Our observations are well
      supported by detailed numerical simulations, which offer additional insight into
      the role of the edge states in Andreev physics. This study paves the way for
      investigating analogous Andreev reflection in a fractional quantum Hall system
      coupled to a superconductor to realize exotic quasiparticles.

PMID- 30192573
TI  - Early Stages of Ultrafast Spin Dynamics in a 3d Ferromagnet.
AB  - Prior to the development of pulsed lasers, one assigned a single local
      temperature to the lattice, the electron gas, and the spins. With the
      availability of ultrafast laser sources, one can now drive the temperature of
      these reservoirs out of equilibrium. Thus, the solid shows new internal degrees
      of freedom characterized by individual temperatures of the electron gas T_{e},
      the lattice T_{l} and the spins T_{s}. We demonstrate an analogous behavior in
      the spin polarization of a ferromagnet in an ultrafast demagnetization
      experiment: At the Fermi energy, the polarization is reduced faster than at
      deeper in the valence band. Therefore, on the femtosecond time scale, the
      magnetization as a macroscopic quantity does not provide the full picture of the
      spin dynamics: The spin polarization separates into different parts similar to
      how the single temperature paradigm changed with the development of ultrafast
      lasers.

PMID- 30192574
TI  - Intrinsic Spin and Orbital Hall Effects from Orbital Texture.
AB  - We show theoretically that both the intrinsic spin Hall effect (SHE) and orbital
      Hall effect (OHE) can arise in centrosymmetric systems through momentum-space
      orbital texture, which is ubiquitous even in centrosymmetric systems unlike spin
      texture. The OHE occurs even without spin-orbit coupling (SOC) and is converted
      into the SHE through SOC. The resulting spin Hall conductivity is large
      (comparable to that of Pt) but depends on the SOC strength in a nonmonotonic way.
      This mechanism is stable against orbital quenching. This work suggests a path for
      an ongoing search for materials with stronger SHE. It also calls for experimental
      efforts to probe orbital degrees of freedom in the OHE and SHE. Possible ways for
      experimental detection are briefly discussed.

PMID- 30192575
TI  - Binomial Spin Glass.
AB  - To establish a unified framework for studying both discrete and continuous
      coupling distributions, we introduce the binomial spin glass, a class of models
      where the couplings are sums of m identically distributed Bernoulli random
      variables. In the continuum limit m->infinity, the class reduces to one with
      Gaussian couplings, while m=1 corresponds to the +/-J spin glass. We demonstrate
      that for short-range Ising models on d-dimensional hypercubic lattices the ground
      state entropy density for N spins is bounded from above by (sqrt[d/2m]+1/N)ln2,
      and further show that the actual entropies follow the scaling behavior implied by
      this bound. We thus uncover a fundamental noncommutativity of the thermodynamic
      and continuous coupling limits that leads to the presence or absence of
      degeneracies depending on the precise way the limits are taken. Exact
      calculations of defect energies reveal a crossover length scale
      L^{*}(m)~L^{kappa} below which the binomial spin glass is indistinguishable from
      the Gaussian system. Since kappa=-1/(2theta), where theta is the spin-stiffness
      exponent, discrete couplings become irrelevant at large scales for systems with a
      finite-temperature spin-glass phase.

PMID- 30192576
TI  - Mutual Neutralization of O^{-} with O^{+} and N^{+} at Subthermal Collision
      Energies.
AB  - We have measured total absolute cross sections for the mutual neutralization (MN)
      of O^{-} with O^{+} and N^{+}. A fine resolution (of about 50 meV) in the kinetic
      energy spectra of the product neutral atoms allows unique identification of the
      atomic states participating in the mutual neutralization process. Cross sections
      and branching ratios have also been calculated down to 1 meV center-of-mass
      collision energy for these two systems, with a multichannel Landau-Zener model
      and an asymptotic method for the ionic-covalent coupling matrix elements. The
      importance of two-electron processes in one-electron transfer is demonstrated by
      the dominant contribution of a core-excited configuration of the nitrogen atom in
      N^{+}+O^{-} collisions. This effect is partially accounted for by introducing
      configuration mixing in the evaluation of coupling matrix elements.

PMID- 30192577
TI  - Constraining a Thin Dark Matter Disk with Gaia.
AB  - If a component of the dark matter has dissipative interactions, it could collapse
      to form a thin dark disk in our Galaxy that is coplanar with the baryonic disk.
      It has been suggested that dark disks could explain a variety of observed
      phenomena, including periodic comet impacts. Using the first data release from
      the Gaia space observatory, we search for a dark disk via its effect on stellar
      kinematics in the Milky Way. Our new limits disfavor the presence of a thin dark
      matter disk, and we present updated measurements on the total matter density in
      the Solar neighborhood.

PMID- 30192580
TI  - Measuring the Single-Photon Temporal-Spectral Wave Function.
AB  - Temporal-spectral modes of light provide a fundamental window into the nature of
      quantum systems and offer a robust means for information encoding. Methods to
      precisely characterize the temporal-spectral state of light at the single-photon
      level thus play a central role in understanding single-photon sources and their
      applications in emerging optical quantum technologies. Here we demonstrate an
      optical reference-free method, which melds techniques from ultrafast metrology
      and single-photon spectral detection, to characterize the pulse-mode structure of
      heralded single photons.

PMID- 30192579
TI  - Constraints on a Spin-Dependent Exotic Interaction between Electrons with Single
      Electron Spin Quantum Sensors.
AB  - A new laboratory bound on the axial-vector mediated interaction between electron
      spins at micrometer scale is established with single nitrogen-vacancy (NV)
      centers in diamond. A single crystal of p-terphenyl doped pentacene-d_{14} under
      laser pumping provides the source of polarized electron spins. Based on the
      measurement of polarization signal via nitrogen-vacancy centers, we set a
      constraint for the exotic electron-electron coupling g_{A}^{e}g_{A}^{e}, within
      the force range from 10 to 900  MUm. The obtained upper bound of the coupling at
      500  MUm is |g_{A}^{e}g_{A}^{e}/4pihc|<=1.8*10^{-19}, which is one order of
      magnitude more stringent than a previous experiment. Our result shows that the NV
      center can be a promising platform for searching for new particles predicted by
      theories beyond the standard model.

PMID- 30192581
TI  - Thermodynamic Bound on Heat-to-Power Conversion.
AB  - In systems described by the scattering theory, there is an upper bound, lower
      than Carnot, on the efficiency of steady-state heat-to-work conversion at a given
      output power. We show that interacting systems can overcome such bound and
      saturate, in the thermodynamic limit, the much more favorable linear-response
      bound. This result is rooted in the possibility for interacting systems to
      achieve the Carnot efficiency at the thermodynamic limit without delta-energy
      filtering, so that large efficiencies can be obtained without greatly reducing
      power.

PMID- 30192578
TI  - Bend-Induced Twist Waves and the Structure of Nucleosomal DNA.
AB  - Recent work indicates that twist-bend coupling plays an important role in DNA
      micromechanics. Here we investigate its effect on bent DNA. We provide an
      analytical solution of the minimum-energy shape of circular DNA, showing that
      twist-bend coupling induces sinusoidal twist waves. This solution is in excellent
      agreement with both coarse-grained simulations of minicircles and nucleosomal DNA
      data, which is bent and wrapped around histone proteins in a superhelical
      conformation. Our analysis shows that the observed twist oscillation in
      nucleosomal DNA, so far attributed to the interaction with the histone proteins,
      is an intrinsic feature of free bent DNA, and should be observable in other
      protein-DNA complexes.

PMID- 30192582
TI  - Fast Detection of a Weak Signal by a Stochastic Resonance Induced by a Coherence
      Resonance in an Excitable GaAs/Al_{0.45}Ga_{0.55}As Superlattice.
AB  - The effect of a coherence resonance is observed experimentally in a
      GaAs/Al_{0.45}Ga_{0.55}As superlattice under dc bias at room temperature, which
      is driven by noise. For an applied voltage, for which no current self
      oscillations are observed, regular current self-oscillations with a frequency of
      about 82 MHz are induced by exceeding a certain noise amplitude. In addition, a
      novel kind of a stochastic resonance is identified, which is triggered by the
      coherence resonance. This stochastic resonance appears when the device is driven
      by an external ac signal with a frequency, which is relatively close to that of
      the regular current self-oscillations at the coherence resonance. The intrinsic
      oscillation mode in the coherence resonance is found to be phase locked by an
      extremely weak ac signal. It is demonstrated that an excitable superlattice
      device can be used for the fast detection of weak signals submerged in noise.
      These results are very well reproduced by results using numerical simulations
      based on a sequential resonant tunneling model of nonlinear electron transport in
      semiconductor superlattices.

PMID- 30192584
TI  - Midinfrared Plasmonic Valleytronics in Metagate-Tuned Graphene.
AB  - A valley plasmonic crystal for graphene surface plasmons is proposed. We
      demonstrate that a designer metagate, placed within a few nanometers of graphene,
      can be used to impose a periodic Fermi energy landscape on graphene. For specific
      metagate geometries and bias voltages, the combined metagate-graphene structure
      is shown to produce complete propagation band gaps for the plasmons, and to
      impart them with nontrivial valley-linked topological properties. Sharply curved
      domain walls between differently patterned metagates are shown to guide highly
      localized plasmons without any reflections owing to suppressed intervalley
      scattering. Our approach paves the way for nonmagnetic and dynamically
      reconfigurable topological nanophotonic devices.

PMID- 30192583
TI  - Comment on "Experimental Verification of a Jarzynski-Related Information
      Theoretic Equality by a Single Trapped Ion".

PMID- 30192585
TI  - Primordial Black Holes from Sound Speed Resonance during Inflation.
AB  - We report on a novel phenomenon of the resonance effect of primordial density
      perturbations arisen from a sound speed parameter with an oscillatory behavior,
      which can generically lead to the formation of primordial black holes in the
      early Universe. For a general inflaton field, it can seed primordial density
      fluctuations, and their propagation is governed by a parameter of sound speed
      square. Once, if this parameter achieves an oscillatory feature for a while
      during inflation, a significant nonperturbative resonance effect on the inflaton
      field fluctuations takes place around a critical length scale, which results in
      significant peaks in the primordial power spectrum. By virtue of this robust
      mechanism, primordial black holes with specific mass function can be produced
      with a sufficient abundance for dark matter in sizable parameter ranges.

PMID- 30192586
TI  - Determination of Interatomic Potentials of He_{2}, Ne_{2}, Ar_{2}, and H_{2} by
      Wave Function Imaging.
AB  - We report on a direct method to measure the interatomic potential energy curve of
      diatomic systems. A cold target recoil ion momentum spectroscopy reaction
      microscope was used to measure the squares of the vibrational wave functions of
      H_{2}, He_{2}, Ne_{2}, and Ar_{2}. The Schrodinger equation relates the curvature
      of the wave function to the potential V(R) and therefore offers a simple but
      elegant way to extract the shape of the potential.

PMID- 30192587
TI  - 3D Imaging and Manipulation of Subsurface Selenium Vacancies in PdSe_{2}.
AB  - Two-dimensional materials such as layered transition-metal dichalcogenides (TMDs)
      are ideal platforms for studying defect behaviors, an essential step towards
      defect engineering for novel material functions. Here, we image the 3D lattice
      locations of selenium-vacancy V_{Se} defects and manipulate them using a scanning
      tunneling microscope (STM) near the surface of PdSe_{2}, a recently discovered
      pentagonal layered TMD. The V_{Se} show a characterisitc charging ring in a
      spatially resolved conductance map, based on which we can determine its
      subsurface lattice location precisely. Using the STM tip, not only can we
      reversibly switch the defect states between charge neutral and charge negative,
      but also trigger migrations of V_{Se} defects. This allows a demonstration of
      direct "writing" and "erasing" of atomic defects and tracing the diffusion
      pathways. First-principles calculations reveal a small diffusion barrier of
      V_{Se} in PdSe_{2}, which is much lower than S vacancy in MoS_{2} or an O vacancy
      in TiO_{2}. This finding opens an opportunity of defect engineering in PdSe_{2}
      for such as controlled phase transformations and resistive-switching memory
      device application.

PMID- 30192588
TI  - Emergent de Sitter Epoch of the Quantum Cosmos from Loop Quantum Cosmology.
AB  - The quantum nature of the big bang is reexamined in the framework of loop quantum
      cosmology. The strict application of a regularization procedure to the
      Hamiltonian, originally developed for the Hamiltonian in loop quantum gravity,
      leads to a qualitative modification of the bounce paradigm. Quantum gravity
      effects still lead to a quantum bounce connecting deterministically large
      classical universes. However, the evolution features a large epoch of a de Sitter
      universe, with an emergent cosmological constant of Planckian order, smoothly
      transiting into a spatially flat expanding universe.

PMID- 30192589
TI  - Diffractive Electron-Nucleus Scattering and Ancestry in Branching Random Walks.
AB  - We point out an analogy between diffractive electron-nucleus scattering events
      and realizations of one-dimensional branching random walks selected according to
      the height of the genealogical tree of the particles near their boundaries. This
      correspondence is made transparent in an event-by-event picture of diffraction,
      emphasizing the statistical properties of gluon evolution, from which new
      quantitative predictions straightforwardly follow: we are able to determine the
      distribution of the total invariant mass produced diffractively, which is an
      interesting observable that can potentially be measured at a future electron-ion
      collider.

PMID- 30192591
TI  - Ultrahigh-Density Spin-Polarized H and D Observed via Magnetization Quantum
      Beats.
AB  - We measure nuclear and electron spin-polarized H and D densities of at least
      10^{19}  cm^{-3} with ~10  ns lifetimes, from the photodissociation of HBr and DI
      with circularly polarized UV light pulses. This density is ~6 orders of magnitude
      higher than that produced by conventional continuous-production methods and,
      surprisingly, at least 100 times higher than expected densities for this
      photodissociation method. We observe the hyperfine quantum beating of the H and D
      magnetization with a pickup coil, i.e., the respective 0.7 and 3 ns periodic
      transfer of polarization from the electrons to the nuclei and back. The 10^{19} 
      cm^{-3} spin-polarized H and D density is sufficient for laser-driven ion
      acceleration of spin-polarized electrons, protons, or deuterons, the preparation
      of nuclear-spin-polarized molecules, and the demonstration of spin-polarized D-T
      or D-^{3}He laser fusion, for which a reactivity enhancement of ~50% is expected.

PMID- 30192590
TI  - Elastic Softness of Hybrid Lead Halide Perovskites.
AB  - Much recent attention has been devoted towards unraveling the microscopic
      optoelectronic properties of hybrid organic-inorganic perovskites. Here we
      investigate by coherent inelastic neutron scattering spectroscopy and Brillouin
      light scattering, low frequency acoustic phonons in four different hybrid
      perovskite single crystals: MAPbBr_{3}, FAPbBr_{3}, MAPbI_{3}, and alpha
      FAPbI_{3} (MA: methylammonium, FA: formamidinium). We report a complete set of
      elastic constants characterized by a very soft shear modulus C_{44}. Further, a
      tendency towards an incipient ferroelastic transition is observed in FAPbBr_{3}.
      We observe a systematic lower sound group velocity in the technologically
      important iodide-based compounds compared to the bromide-based ones. The findings
      suggest that low thermal conductivity and hot phonon bottleneck phenomena are
      expected to be enhanced by low elastic stiffness, particularly in the case of the
      ultrasoft alpha-FAPbI_{3}.

PMID- 30192571
TI  - Observation of the Semileptonic Decay D^{0}->a_{0}(980)^{-}e^{+}nu_{e} and
      Evidence for D^{+}->a_{0}(980)^{0}e^{+}nu_{e}.
AB  - Using an e^{+}e^{-} collision data sample of 2.93  fb^{-1} collected at a center
      of-mass energy of 3.773 GeV by the BESIII detector at BEPCII, we report the
      observation of D^{0}->a_{0}(980)^{-}e^{+}nu_{e} and evidence for D^{+}
      >a_{0}(980)^{0}e^{+}nu_{e} with significances of 6.4sigma and 2.9sigma,
      respectively. The absolute branching fractions are determined to be B(D^{0}
      >a_{0}(980)^{-}e^{+}nu_{e})*B(a_{0}(980)^{-}->etapi^{-})=[1.33_{
      0.29}^{+0.33}(stat)+/-0.09(syst)]*10^{-4} and B(D^{+}
      >a_{0}(980)^{0}e^{+}nu_{e})*B(a_{0}(980)^{0}->etapi^{0})=[1.66_{
      0.66}^{+0.81}(stat)+/-0.11(syst)]*10^{-4}. This is the first time the a_{0}(980)
      meson has been measured in a D^{0} semileptonic decay, which would open one more
      interesting page in the investigation of the nature of the puzzling a_{0}(980)
      states.

PMID- 30192592
TI  - Correlation Function of High-Threshold Regions and Application to the Initial
      Small-Scale Clustering of Primordial Black Holes.
AB  - Primordial black holes (PBHs) have been brought back into the spotlight by LIGO's
      first direct detection of a binary-black-hole merger. One of the poorly
      understood properties of PBHs is how clustered they are at formation. It has
      important implications on the efficacy of their merging in the early Universe, as
      well as on observational constraints. In this work, we study the initial
      clustering of PBHs formed from the gravitational collapse of large density
      fluctuations in the early Universe. We give a simple and general argument showing
      that, in this scenario, we do not expect clustering on very small scales beyond
      what is expected from a random, Poisson distribution. We illustrate this result
      explicitly in the case where the underlying density field is Gaussian. We
      moreover derive a new analytic expression for the two-point correlation function
      of large-threshold fluctuations, generalizing previous results to arbitrary
      separation, and with broader implications than the clustering of PBHs.

PMID- 30192595
TI  - Constraints on Scattering of keV-TeV Dark Matter with Protons in the Early
      Universe.
AB  - We present the first cosmological constraint on dark matter scattering with
      protons in the early Universe for the entire range of dark matter masses between
      1 keV and 1 TeV. This constraint is derived from the Planck measurements of the
      cosmic microwave background (CMB) temperature and polarization anisotropy, and
      the CMB lensing anisotropy. It improves upon previous CMB constraints by many
      orders of magnitude, where limits are available, and closes the gap in coverage
      for low-mass dark matter candidates. We focus on two canonical interaction
      scenarios: spin-independent and spin-dependent scattering with no velocity
      dependence. Our results exclude (with 95% confidence) spin-independent
      interactions with cross sections greater than 5.3*10^{-27}  cm^{2} for 1 keV,
      3.0*10^{-26}  cm^{2} for 1 MeV, 1.7*10^{-25}  cm^{2} for 1 GeV, and 1.6*10^{-23} 
      cm^{2} for 1 TeV dark matter mass. Finally, we discuss the implications of this
      study for dark matter physics and future observations.

PMID- 30192598
TI  - Fundamental Limitations for Measurements in Quantum Many-Body Systems.
AB  - Dynamical measurement schemes are an important tool for the investigation of
      quantum many-body systems, especially in the age of quantum simulation. Here, we
      address the question whether generic measurements can be implemented efficiently
      if we have access to a certain set of experimentally realizable measurements and
      can extend it through time evolution. For the latter, two scenarios are
      considered: (a) evolution according to unitary circuits and (b) evolution due to
      Hamiltonians that we can control in a time-dependent fashion. We find that the
      time needed to realize a certain measurement to a predefined accuracy scales in
      general exponentially with the system size-posing a fundamental limitation. The
      argument is based on the construction of epsilon-packings for manifolds of
      observables with identical spectra and a comparison of their cardinalities to
      those of epsilon-coverings for quantum circuits and unitary time-evolution
      operators. The former is related to the study of Grassmann manifolds.

PMID- 30192599
TI  - Asymmetric and Symmetric Exchange in a Generalized 2D Rashba Ferromagnet.
AB  - Dzyaloshinskii-Moriya interaction (DMI) is investigated in a 2D ferromagnet (FM)
      with spin-orbit interaction of Rashba type at finite temperatures. The FM is
      described in the continuum limit by an effective s-d model with arbitrary
      dependence of spin-orbit coupling (SOC) and kinetic energy of itinerant electrons
      on the absolute value of momentum. In the limit of weak SOC, we derive a general
      expression for the DMI constant D from a microscopic analysis of the electronic
      grand potential. We compare D with the exchange stiffness A and show that, to the
      leading order in small SOC strength alpha_{R}, the conventional relation
      D=(4malpha_{R}/h)A, in general, does not hold beyond the Bychkov-Rashba model.
      Moreover, in this model, both A and D vanish at zero temperature in the metal
      regime (i.e., when two spin sub-bands are partly occupied). For nonparabolic
      bands or nonlinear Rashba coupling, these coefficients are finite and acquire a
      nontrivial dependence on the chemical potential that demonstrates the possibility
      to control the size and chirality of magnetic textures by adjusting a gate
      voltage.

PMID- 30192597
TI  - Divisibility and Information Flow Notions of Quantum Markovianity for
      Noninvertible Dynamical Maps.
AB  - We analyze the relation between completely positive (CP) divisibility and the
      lack of information backflow for an arbitrary-not necessarily invertible
      dynamical map. It is well known that CP divisibility always implies a lack of
      information backflow. Moreover, these two notions are equivalent for invertible
      maps. In this Letter, it is shown that for a map which is not invertible the lack
      of information backflow always implies the existence of a completely positive
      propagator which, however, needs not be trace preserving. Interestingly, for a
      wide class of image nonincreasing dynamical maps, this propagator becomes trace
      preserving as well, and hence, the lack of information backflow implies CP
      divisibility. This result sheds new light into the structure of the time-local
      generators giving rise to CP-divisible evolutions. We show that if the map is not
      invertible then positivity of dissipation/decoherence rates is no longer
      necessary for CP divisibility.

PMID- 30192594
TI  - Test of Local Realism into the Past without Detection and Locality Loopholes.
AB  - Inspired by the recent remarkable progress in the experimental test of local
      realism, we report here such a test that achieves an efficiency greater than
      (78%)^{2} for entangled photon pairs separated by 183 m. Further utilizing the
      randomness in cosmic photons from pairs of stars on the opposite sides of the sky
      for the measurement setting choices, we not only close the locality and detection
      loopholes simultaneously, but also test the null hypothesis against local hidden
      variable mechanisms for events that took place 11 years ago (13 orders of
      magnitude longer than previous experiments). After considering the bias in
      measurement setting choices, we obtain an upper bound on the p value of 7.87*10^{
      4}, which clearly indicates the rejection with high confidence of potential local
      hidden variable models. One may further push the time constraint on local hidden
      variable mechanisms deep into the cosmic history by taking advantage of the
      randomness in photon emissions from quasars with large aperture telescopes.

PMID- 30192600
TI  - Nonlinear Spectroscopy with X-Ray Two-Photon Absorption in Metallic Copper.
AB  - X-ray two-photon absorption (TPA) spectrum of metallic copper is measured using a
      free-electron laser (XFEL). The spectrum differs from that measured by the
      conventional one-photon absorption (OPA), and characterized by a peak below the
      Fermi level, which is assigned to the transition to the 3d state. The impact of
      the XFEL pulse on the OPA spectrum is discussed by analyzing the pulse-energy
      dependence, which indicates that the intrinsic TPA spectrum is measured.

PMID- 30192596
TI  - Low-Mass Dark Matter Search with the DarkSide-50 Experiment.
AB  - We present the results of a search for dark matter weakly interacting massive
      particles (WIMPs) in the mass range below 20  GeV/c^{2} using a target of low
      radioactivity argon with a 6786.0 kg d exposure. The data were obtained using the
      DarkSide-50 apparatus at Laboratori Nazionali del Gran Sasso. The analysis is
      based on the ionization signal, for which the DarkSide-50 time projection chamber
      is fully efficient at 0.1  keVee. The observed rate in the detector at 0.5  keVee
      is about 1.5  event/keVee/kg/d and is almost entirely accounted for by known
      background sources. We obtain a 90% C.L. exclusion limit above 1.8  GeV/c^{2} for
      the spin-independent cross section of dark matter WIMPs on nucleons, extending
      the exclusion region for dark matter below previous limits in the range 1.8-6 
      GeV/c^{2}.

PMID- 30192606
TI  - Strong Spin-Orbit Contribution to the Hall Coefficient of Two-Dimensional Hole
      Systems.
AB  - Classical charge transport, such as longitudinal and Hall currents in weak
      magnetic fields, is usually not affected by quantum phenomena. Yet relativistic
      quantum mechanics is at the heart of the spin-orbit interaction, which has been
      at the forefront of efforts to realize spin-based electronics, new phases of
      matter, and topological quantum computing. In this work we demonstrate that
      quantum spin dynamics induced by the spin-orbit interaction is directly
      observable in classical charge transport. We determine the Hall coefficient R_{H}
      of two-dimensional hole systems at low magnetic fields and show that it has a
      sizable spin-orbit contribution, which depends on the density p, is independent
      of temperature, is a strong function of the top gate electric field, and can
      reach ~20% of the total. We provide a general method for extracting the spin
      orbit parameter from magnetotransport data, applicable even at higher
      temperatures where Shubnikov-de Haas oscillations and weak antilocalization are
      difficult to observe. Our work will enable experimentalists to measure spin-orbit
      parameters without requiring large magnetic fields, ultralow temperatures, or
      optical setups.

PMID- 30192603
TI  - All-Loop Singularities of Scattering Amplitudes in Massless Planar Theories.
AB  - In massless quantum field theories the Landau equations are invariant under graph
      operations familiar from the theory of electrical circuits. Using a theorem on
      the Y-Delta reducibility of planar circuits we prove that the set of first-type
      Landau singularities of an n-particle scattering amplitude in any massless planar
      theory, at any finite loop order, is a subset of those of a certain n-particle
      ?(n-2)^{2}/4?-loop "ziggurat" graph. We determine this singularity locus
      explicitly for n=6 and find that it corresponds precisely to the vanishing of the
      symbol letters familiar from the hexagon bootstrap in supersymmetric Yang-Mills
      (SYM) theory. Further implications for SYM theory are discussed.

PMID- 30192602
TI  - Spin Polarization through Floquet Resonances in a Driven Central Spin Model.
AB  - Adiabatically varying the driving frequency of a periodically driven many-body
      quantum system can induce controlled transitions between resonant eigenstates of
      the time-averaged Hamiltonian, corresponding to adiabatic transitions in the
      Floquet spectrum and presenting a general tool in quantum many-body control.
      Using the central spin model as an application, we show how such controlled
      driving processes can lead to a polarization-based decoupling of the central spin
      from its decoherence-inducing environment at resonance. While it is generally
      impossible to obtain the exact Floquet Hamiltonian in driven interacting systems,
      we exploit the integrability of the central spin model to show how techniques
      from quantum quenches can be used to explicitly construct the Floquet Hamiltonian
      in a restricted many-body basis and model Floquet resonances.

PMID- 30192604
TI  - Cosmic Bell Test Using Random Measurement Settings from High-Redshift Quasars.
AB  - In this Letter, we present a cosmic Bell experiment with polarization-entangled
      photons, in which measurement settings were determined based on real-time
      measurements of the wavelength of photons from high-redshift quasars, whose light
      was emitted billions of years ago; the experiment simultaneously ensures
      locality. Assuming fair sampling for all detected photons and that the wavelength
      of the quasar photons had not been selectively altered or previewed between
      emission and detection, we observe statistically significant violation of Bell's
      inequality by 9.3 standard deviations, corresponding to an estimated p value of
      ?7.4*10^{-21}. This experiment pushes back to at least ~7.8  Gyr ago the most
      recent time by which any local-realist influences could have exploited the
      "freedom-of-choice" loophole to engineer the observed Bell violation, excluding
      any such mechanism from 96% of the space-time volume of the past light cone of
      our experiment, extending from the big bang to today.

PMID- 30192605
TI  - Dislocation Networks and the Microstructural Origin of Strain Hardening.
AB  - When metals plastically deform, the density of line defects called dislocations
      increases and the microstructure is continuously refined, leading to the strain
      hardening behavior. Using discrete dislocation dynamics simulations, we
      demonstrate the fundamental role of junction formation in connecting dislocation
      microstructure evolution and strain hardening in face-centered cubic (fcc) Cu.
      The dislocation network formed consists of line segments whose lengths closely
      follow an exponential distribution. This exponential distribution is a
      consequence of junction formation, which can be modeled as a one-dimensional
      Poisson process. According to the exponential distribution, two non-dimensional
      parameters control microstructure evolution, with the hardening rate dictated by
      the rate of stable junction formation. Among the types of junctions in fcc
      crystals, we find that glissile junctions make the dominant contribution to
      strain hardening.

PMID- 30192609
TI  - Lambda-Enhanced Imaging of Molecules in an Optical Trap.
AB  - We report on nondestructive imaging of optically trapped calcium monofluoride
      molecules using in situ Lambda-enhanced gray molasses cooling. 200 times more
      fluorescence is obtained compared to destructive on-resonance imaging, and the
      trapped molecules remain at a temperature of 20  MUK. The achieved number of
      scattered photons makes possible nondestructive single-shot detection of single
      molecules with high fidelity.

PMID- 30192610
TI  - Fractionalized Metal in a Falicov-Kimball Model.
AB  - Quantum Monte Carlo simulations reveal an exotic metallic phase with a single
      particle gap but gapless spin and charge excitations and a nonsaturating
      resistivity in a two-dimensional SU(2) Falicov-Kimball model. An exact duality
      between this model and an unconstrained slave-spin theory leads to a
      classification of the phase as a fractionalized or orthogonal metal whose low
      energy excitations have different quantum numbers than the original electrons.
      Whereas the fractionalized metal corresponds to the regime of disordered slave
      spins, the regime of ordered slave spins is a Fermi liquid. At a critical
      temperature, an Ising phase transition to a spontaneously generated constrained
      slave-spin theory of the Hubbard model is observed.

PMID- 30192607
TI  - Cavity-Enhanced Raman Emission from a Single Color Center in a Solid.
AB  - We demonstrate cavity-enhanced Raman emission from a single atomic defect in a
      solid. Our platform is a single silicon-vacancy center in diamond coupled with a
      monolithic diamond photonic crystal cavity. The cavity enables an unprecedented
      frequency tuning range of the Raman emission (100 GHz) that significantly exceeds
      the spectral inhomogeneity of silicon-vacancy centers in diamond nanostructures.
      We also show that the cavity selectively suppresses the phonon-induced
      spontaneous emission that degrades the efficiency of Raman photon generation. Our
      results pave the way towards photon-mediated many-body interactions between solid
      state quantum emitters in a nanophotonic platform.

PMID- 30192608
TI  - Experimental Time-Resolved Interference with Multiple Photons of Different
      Colors.
AB  - Interference of multiple photons via a linear-optical network has profound
      applications for quantum foundation, quantum metrology, and quantum computation.
      Particularly, a boson sampling experiment with a moderate number of photons
      becomes intractable even for the most powerful classical computers. Scaling up
      from small-scale experiments requires highly indistinguishable single photons,
      which may be prohibited for many physical systems. Here we report a time-resolved
      multiphoton interference experiment by using photons not overlapping in their
      frequency spectra from three atomic-ensemble quantum memories. Time-resolved
      measurement enables us to observe nonclassical multiphoton correlation
      landscapes, which agree well with theoretical calculations. Symmetries in the
      landscapes are identified to reflect symmetries of the optical network. Our
      experiment can be further extended to realize boson sampling with many photons
      and plenty of modes, which thus may provide a route towards quantum supremacy
      with nonidentical photons.

PMID- 30192611
TI  - Experimental Demonstration of an Anisotropic Exceptional Point.
AB  - Exceptional points (EPs) associated with a square-root singularity have been
      found in many non-Hermitian systems. In most of the studies, the EPs found are
      isotropic, meaning that the same singular behavior is obtained independent of the
      direction from which they are approached in the parameter space. In this Letter,
      we demonstrate both theoretically and experimentally the existence of an
      anisotropic EP in an acoustic system that shows different singular behaviors when
      the anisotropic EP is approached from different directions in the parameter
      space. Such an anisotropic EP arises from the coalescence of two square-root EPs
      having the same chirality.

PMID- 30192612
TI  - Localizing the Shape Transition in Neutron-Deficient Selenium.
AB  - Neutron-deficient selenium isotopes are thought to undergo a rapid shape change
      from a prolate deformation near the line of beta stability towards oblate
      deformation around the line of N=Z. The point at which this shape change occurs
      is unknown, with inconsistent predictions from available theoretical models. A
      common feature in the models is the delicate nature of the point of transition,
      with the introduction of even a modest spin to the system sufficient to change
      the ordering of the prolate and oblate configurations. We present a measurement
      of the quadrupole moment of the first-excited state in radioactive ^{72}Se-a
      potential point of transition-by safe Coulomb excitation. This is the first low
      energy Coulomb excitation to be performed with a rare-isotope beam at the
      reaccelerated beam facility at the National Superconducting Cyclotron Laboratory.
      By demonstrating a negative spectroscopic quadrupole moment for the first-excited
      2^{+} state, it is found that any low-spin shape change in neutron-deficient
      selenium does not occur until ^{70}Se.

PMID- 30192613
TI  - Nonlocal Coupling between Antiferromagnets and Ferromagnets in Cavities.
AB  - Microwaves couple to magnetic moments in both ferromagnets and antiferromagnets.
      Although the magnons in ferromagnets and antiferromagnets radically differ, they
      can become entangled via strong coupling to the same microwave mode in a cavity.
      The equilibrium configuration of the magnetic moments crucially governs the
      coupling between the different magnons, because the antiferromagnetic and
      ferromagnetic magnons have opposite spins when their dispersion relations cross.
      We derive analytical expressions for the coupling strengths and find that the
      coupling between antiferromagnets and ferromagnets is comparable to the coupling
      between two ferromagnets. Our findings reveal a robust link between cavity
      spintronics with ferromagnets and antiferromagnets.

PMID- 30192614
TI  - Thermal Temperature Measurements of Inertial Fusion Implosions.
AB  - Accurate measurement of the thermal temperature in inertially confined fusion
      plasmas is essential for characterizing ignition performance and validating the
      basic physics understanding of the stagnation conditions. We present experimental
      results from cryogenic deuterium-tritium implosions on the National Ignition
      Facility using a differential filter spectrometer designed to measure the thermal
      electron temperature from x-ray continuum emission from the stagnated plasma.
      Furthermore, electron temperature measurements, used in conjunction with the
      Doppler-broadened DT neutron spectra, allow one to infer the partition of energy
      in the hot spot between internal energy and unconverted kinetic energy.

PMID- 30192615
TI  - Predictions for the Sky-Averaged Depth of the 21 cm Absorption Signal at High
      Redshift in Cosmologies with and without Nonbaryonic Cold Dark Matter.
AB  - We consider the 21 cm absorption signal expected at high redshift in cosmologies
      with and without nonbaryonic cold dark matter. The expansion of the early
      Universe decelerates strongly with dark matter, but approximately coasts without
      it. This results in a different path length across the epochs when absorption is
      expected, with the consequence that the absorption is predicted to be a factor of
      ~2 greater without dark matter than with it. Observation of such a signal would
      motivate consideration of extended theories of gravity in lieu of dark matter.

PMID- 30192616
TI  - Optical Cooling of Magnons.
AB  - Inelastic scattering of light by spin waves generates an energy flow between the
      light and magnetization fields, a process that can be enhanced and controlled by
      concentrating the light in magneto-optical resonators. Here, we model the cooling
      of a sphere made of a magnetic insulator, such as yttrium iron garnet, using a
      monochromatic laser source. When the magnon lifetimes are much larger than the
      optical ones, we can treat the latter as a Markovian bath for magnons. The steady
      state magnons are canonically distributed with a temperature that is controlled
      by the light intensity. We predict that such a cooling process can significantly
      reduce the temperature of the magnetic order within current technology.

PMID- 30192617
TI  - Glass Transition in Supercooled Liquids with Medium-Range Crystalline Order.
AB  - The origin of the rapid dynamical slowdown in glass forming liquids in the growth
      of static length scales, possibly associated with identifiable structural
      ordering, is a much debated issue. Growth of medium range crystalline order
      (MRCO) has been observed in various model systems to be associated with glassy
      behavior. Such observations raise the question of whether molecular mechanisms
      for the glass transition in liquids with and without MRCO are the same. In this
      study we perform extensive molecular dynamics simulations of a number of glass
      forming liquids and show that the static and dynamic properties of glasses with
      MRCO are different from those of other glass forming liquids with no predominant
      local order. We also resolve an important issue regarding the so-called point-to
      set method for determining static length scales, and demonstrate it to be a
      robust method for determining static correlation lengths in glass formers.

PMID- 30192618
TI  - Nonadditivity of Optical and Casimir-Polder Potentials.
AB  - An atom irradiated by an off-resonant laser field near a surface is expected to
      experience the sum of two fundamental potentials, the optical potential of the
      laser field and the Casimir-Polder potential of the surface. Here, we report a
      new nonadditive potential, namely, the laser-induced Casimir-Polder potential,
      which arises from a correlated coupling of the atom with both the laser and the
      quantum vacuum. We apply this result to an experimentally realizable scenario of
      an atomic mirror with an evanescent laser beam leaking out of a surface. We show
      that the nonadditive term is significant for realistic experimental parameters,
      transforming potential barriers into potential wells, which can be used to trap
      atoms near surfaces.

PMID- 30192619
TI  - Quantum Field Theory of Nematic Transitions in Spin-Orbit-Coupled Spin-1 Polar
      Bosons.
AB  - We theoretically study an ultracold gas of spin-1 polar bosons in a one
      dimensional continuum, which are subject to linear and quadratic Zeeman fields
      and a Raman induced spin orbit coupling. Concentrating on the regime in which the
      background fields can be treated perturbatively, we analytically solve the model
      in its low-energy sector; i.e., we characterize the relevant phases and the
      quantum phase transitions between them. Depending on the sign of the effective
      quadratic Zeeman field epsilon, two superfluid phases with distinct nematic order
      appear. In addition, we uncover a spin-disordered superfluid phase at strong
      coupling. We employ a combination of renormalization group calculations and
      duality transformations to access the nature of the phase transitions. At
      epsilon=0, a line of spin-charge separated pairs of Luttinger liquids divides the
      two nematic phases, and the transition to the spin-disordered state at strong
      coupling is of the Berezinskii-Kosterlitz-Thouless type. In contrast, at
      epsilon?0, the quantum critical theory separating nematic and strong coupling
      spin-disordered phases contains a Luttinger liquid in the charge sector that is
      coupled to a Majorana fermion in the spin sector (i.e., the critical theory at
      finite epsilon maps to a quantum critical Ising model that is coupled to the
      charge Luttinger liquid). Because of an emergent Lorentz symmetry, both have the
      same logarithmically diverging velocity. We discuss the experimental signatures
      of our findings that are relevant to ongoing experiments in ultracold atomic
      gases of ^{23}Na.

PMID- 30192620
TI  - Carrier Lifetimes and Polaronic Mass Enhancement in the Hybrid Halide Perovskite
      CH_{3}NH_{3}PbI_{3} from Multiphonon Frohlich Coupling.
AB  - We elucidate the nature of the electron-phonon interaction in the archetypal
      hybrid perovskite CH_{3}NH_{3}PbI_{3} using ab initio many-body calculations and
      an exactly solvable model. We demonstrate that electrons and holes near the band
      edges primarily interact with three distinct groups of longitudinal-optical
      vibrations, in order of importance: the stretching of the Pb-I bond, the bending
      of the Pb-I-Pb bonds, and the libration of the organic cations. These polar
      phonons induce ultrafast intraband carrier relaxation over timescales of 6-30 fs
      and yield polaron effective masses 28% heavier than the bare band masses. These
      findings allow us to rationalize previous experimental observations and provide a
      key to understanding carrier dynamics in halide perovskites.

PMID- 30192621
TI  - Topological Superconductivity in Twisted Multilayer Graphene.
AB  - We study a minimal Hubbard model for electronically driven superconductivity in a
      correlated flat miniband resulting from the superlattice modulation of a twisted
      graphene multilayer. The valley degree of freedom drastically modifies the nature
      of the preferred pairing states, favoring spin triplet d+id order with a valley
      singlet structure. We identify two candidates in this class, which are both
      topological superconductors. These states support half-vortices carrying half the
      usual superconducting flux quantum hc/(4e), and have topologically protected
      gapless edge states.

PMID- 30192622
TI  - How Does a Locally Constrained Quantum System Localize?
AB  - At low energy, the dynamics of excitations of many physical systems are locally
      constrained. Examples include frustrated antiferromagnets, fractional quantum
      Hall fluids, and Rydberg atoms in the blockaded regime. Can such locally
      constrained systems be fully many-body localized? In this Letter, we answer this
      question affirmatively and elucidate the structure of the accompanying quasilocal
      integrals of motion. By studying disordered spin chains subject to a projection
      constraint in the z direction, we show that full many-body localization (MBL) is
      stable at strong z-field disorder and identify a new mechanism of localization
      through resonance at strong transverse disorder. However, MBL is not guaranteed;
      the constraints can "frustrate" the tendency of the spins to align with the
      transverse fields and lead to full thermalization or criticality. We further
      provide evidence that the transition is discontinuous in local observables with
      large sample-to-sample variations. Our dynamical phase diagram is accessible in
      current Rydberg atomic experiments which realize programmable constrained Ising
      Hamiltonians.

PMID- 30192623
TI  - Charge Excitation Dynamics in Bosonic Fractional Chern Insulators.
AB  - The experimental realization of the Harper-Hofstadter model in ultracold atomic
      gases has placed fractional states of matter in these systems within reach-a
      fractional Chern insulator state (FCI) is expected to emerge for sufficiently
      strong interactions when half-filling the lowest band. The experimental setups
      naturally allow us to probe the dynamics of this topological state; yet little is
      known about its out-of-equilibrium properties. We explore, using density matrix
      renormalization group simulations, the response of the FCI state to spatially
      localized perturbations. After confirming the static properties of the phase we
      show that the characteristic, gapless features are clearly visible in the edge
      dynamics. We find that a local edge perturbation in this model propagates
      chirally independent of the perturbation strength. This contrasts the behavior of
      single particle models with counterpropagating edge states, such as the
      noninteracting Harper-Hofstadter model, where the chirality is manifest only for
      weak perturbations. Additionally, our simulations show that there is inevitable
      density leakage from the first row of sites into the bulk, preventing a naive
      chiral Luttinger theory interpretation of the dynamics.

PMID- 30192624
TI  - Nuclear Magnetic Field in Solids Detected with Negative-Muon Spin Rotation and
      Relaxation.
AB  - Using an intense negative muon (MU^{-}) source, we have studied the internal
      magnetic fields in a powder sample of magnesium hydride (MgH_{2}). By extracting
      the signal from the MU^{-} captured on Mg nuclei, we found that the negative muon
      spin rotation and relaxation (MU^{-}SR) spectra clearly showed a Kubo-Toyabe-type
      relaxation, which indicates a random magnetic field at the Mg site. The field
      distribution width obtained is very consistent with the predicted value at the Mg
      site estimated by dipole field calculations, supporting our claim to have
      observed the nuclear magnetic fields of hydrogens in MgH_{2}. As is the case with
      MU^{+}SR, MU^{-}SR promises to soon be an indispensable tool for materials
      analyses.

PMID- 30192626
TI  - Measurement of the Entanglement Spectrum of a Symmetry-Protected Topological
      State Using the IBM Quantum Computer.
AB  - Entanglement properties are routinely used to characterize phases of quantum
      matter in theoretical computations. For example, the spectrum of the reduced
      density matrix, or so-called "entanglement spectrum", has become a widely used
      diagnostic for universal topological properties of quantum phases. However, while
      being convenient to calculate theoretically, it is notoriously hard to measure in
      experiments. Here, we use the IBM quantum computer to make the first ever
      measurement of the entanglement spectrum of a symmetry-protected topological
      state. We are able to distinguish its entanglement spectrum from those we measure
      for trivial and long-range ordered states.

PMID- 30192625
TI  - Coherence Resonance and Stochastic Resonance in an Excitable Semiconductor
      Superlattice.
AB  - Collective electron transport causes a weakly coupled semiconductor superlattice
      under dc voltage bias to be an excitable system with 2N+2 degrees of freedom:
      electron densities and fields at N superlattice periods plus the total current
      and the field at the injector. External noise of sufficient amplitude induces
      regular current self-oscillations (coherence resonance) in states that are
      stationary in the absence of noise. Numerical simulations show that these
      oscillations are due to the repeated nucleation and motion of charge dipole waves
      that form at the emitter when the current falls below a critical value. At the
      critical current, the well-to-well tunneling current intersects the contact load
      line. We have determined the device-dependent critical current for the coherence
      resonance from experiments and numerical simulations. We have also described
      through numerical simulations how a coherence resonance triggers a stochastic
      resonance when its oscillation mode becomes locked to a weak ac external voltage
      signal. Our results agree with the experimental observations.

PMID- 30192627
TI  - Coalescence of Two Impurities in a Trapped One-dimensional Bose Gas.
AB  - We study the ground state of a one-dimensional (1D) trapped Bose gas with two
      mobile impurity particles. To investigate this setup, we develop a variational
      procedure in which the coordinates of the impurity particles are slowlike
      variables. We validate our method using the exact results obtained for small
      systems. Then, we discuss energies and pair densities for systems that contain of
      the order of 100 atoms. We show that bosonic noninteracting impurities cluster.
      To explain this clustering, we calculate and discuss induced impurity-impurity
      potentials in a harmonic trap. Further, we compute the force between static
      impurities in a ring (in the manner of the Casimir force), and contrast the two
      effective potentials: the one obtained from the mean-field approximation, and the
      one due to the one-phonon exchange. Our formalism and findings are important for
      understanding (beyond the polaron model) the physics of modern 1D cold-atom
      systems with more than one impurity.

PMID- 30192628
TI  - Edge States and Topological Invariants of Non-Hermitian Systems.
AB  - The bulk-boundary correspondence is among the central issues of non-Hermitian
      topological states. We show that a previously overlooked "non-Hermitian skin
      effect" necessitates redefinition of topological invariants in a generalized
      Brillouin zone. The resultant phase diagrams dramatically differ from the usual
      Bloch theory. Specifically, we obtain the phase diagram of the non-Hermitian Su
      Schrieffer-Heeger model, whose topological zero modes are determined by the non
      Bloch winding number instead of the Bloch-Hamiltonian-based topological number.
      Our work settles the issue of the breakdown of conventional bulk-boundary
      correspondence and introduces the non-Bloch bulk-boundary correspondence.

PMID- 30192629
TI  - Symmetry-Protected Topological Metals.
AB  - We show that sharply defined topological quantum phase transitions are not
      limited to states of matter with gapped electronic spectra. Such transitions may
      also occur between two gapless metallic states both with extended Fermi surfaces.
      The transition is characterized by a discontinuous, but not quantized, jump in an
      off-diagonal transport coefficient. Its sharpness is protected by a symmetry,
      such as, e.g., particle-hole symmetry, which remains unbroken across the
      transition. We present a simple model of this phenomenon, based on 2D p+ip
      superconductor with an applied supercurrent, and discuss its geometrical
      interpretation.

PMID- 30192630
TI  - Vascular mitochondrial respiratory function: the impact of advancing age.
AB  - Little is known about vascular mitochondrial respiratory function and the impact
      of age. Therefore, skeletal muscle feed arteries (SMFAs) were harvested from
      young (33+/-7yrs, n=10), middle (54+/-5yrs, n=10), and old (70+/-7yrs, n=10)
      subjects, and mitochondrial respiration as well as citrate synthase (CS) activity
      were assessed. Complex I (CI) and complex I+II (CI+II), state 3 respiration were
      greater in the young (CI: 10.4+/-0.8, CI+II: 12.4+/-0.8 pmol/s/mg, P<0.05)
      compared to both middle (CI: 7+/-0.6, CI+II: 8.3+/-0.5 pmol/s/mg) and old (CI:
      7.2+/-0.4, CI+II: 7.6+/-0.5 pmol/s/mg) and, in addition to CII state 3, were
      inversely correlated with age (CI: r=-0.56, CI+II: r=-0.7, CII: r=0.4; P<0.05).
      In contrast, state 4 respiration and mitochondria-specific superoxide levels were
      not different across groups. The respiratory control ratio (RCR) was greater in
      the young (2.2+/-0.2, P<0.05) compared to the middle and old (1.4+/-0.1, 1.1+/
      0.1) and inversely correlated with age (r=-0.71, P<0.05). As CS activity was
      inversely correlated with age (r=-0.54, P<0.05), when normalized for
      mitochondrial content, the age-related differences and relationships with state 3
      were ablated. In contrast, mitochondrion-specific state 4 was now lower in the
      young (15+/-1.4 pmol/s/mg/U CS, P<0.05) than the middle and old (23.4+/-3.6,
      27.9+/-3.4 pmol/s/mg/U CS), and correlated with age (r=0.46, P<0.05). Similarly,
      superoxide/CS levels were lower in the young (0.07+/-0.01) than the old (0.19+/
      0.41), and correlated with age (r=0.44, P<0.05). Therefore, with aging vascular
      mitochondrial respiratory function declines, predominantly as a consequence of
      falling mitochondrial content. However, per mitochondrion, aging likely results
      in greater mitochondrial-derived oxidative stress, which may contribute to age
      related vascular dysfunction.

PMID- 30192631
TI  - Sex Differences in the Vascular Function and Related Mechanisms: Role of
      17betaEstradiol.
AB  - The incidence of cardiovascular disease (CVD) is lower in pre-menopausal women
      but increases with age and menopause compared to similar-aged men. Based on the
      prevalence of CVD in the post-menopausal women, sex hormone-dependent mechanisms
      have been postulated to be the primary factors responsible for the protection
      from CVD in pre-menopausal women. Recent Women's Health Initiative studies,
      Cochrane review, ELITE and KEEPS studies suggest that beneficial effects of
      hormone replacement therapy (HRT) are seen in women less than 60 years of age and
      if initiated in less than ten years of menopause. In contrast, the beneficial
      effects of HRT are not seen in women greater than 60 years of age and if
      commenced after ten years of menopause. The higher incidence of CVD and the
      failure of HRT in post-menopausal aged women could be partly associated with
      fundamental differences in the vascular structure and function between men and
      women and in between pre and post-menopausal women, respectively. In this regard,
      previous studies from human and animal studies identified several sex differences
      in the vascular function and the associated mechanisms. Female sex hormone
      17betaEstradiol (17betaE) regulates the majority of these mechanisms. In this
      review, we summarize the sex differences in vascular structure, myogenic
      properties, endothelial-dependent and -independent mechanisms and the role of
      17betaE in the regulation of vascular function.

PMID- 30192632
TI  - Understanding the mechanisms of left ventricle mechanical unloading to achieve
      myocardial recovery.

PMID- 30192635
TI  - Is Cystic Fibrosis Related Diabetes Reversible? New Data on CFTR Potentiation and
      Insulin Secretion.

PMID- 30192633
TI  - Poor Agreement and Imprecision of Respiratory Rate Measurements in Children in a
      Low-Income Setting.

PMID- 30192636
TI  - Power in Numbers: Single-Cell RNA-Seq Strategies to Dissect Complex Tissues.
AB  - The growing scale and declining cost of single-cell RNA-sequencing (RNA-seq) now
      permit a repetition of cell sampling that increases the power to detect rare cell
      states, reconstruct developmental trajectories, and measure phenotype in new
      terms such as cellular variance. The characterization of anatomy and
      developmental dynamics has not had an equivalent breakthrough since
      groundbreaking advances in live fluorescent microscopy. The new resolution
      obtained by single-cell RNA-seq is a boon to genetics because the novel
      description of phenotype offers the opportunity to refine gene function and
      dissect pleiotropy. In addition, the recent pairing of high-throughput genetic
      perturbation with single-cell RNA-seq has made practical a scale of genetic
      screening not previously possible.

PMID- 30192634
TI  - Exposure to Humidifier Disinfectants Increases the Risk of Asthma in Children.

PMID- 30192637
TI  - Tracing My Roots: How I Became a Plant Biologist.
AB  - My trajectory to becoming a plant biologist was shaped by a complex mix of
      scientific, political, sociological, and personal factors. I was trained as a
      microbiologist and molecular biologist in the late 1960s and early 1970s, a time
      of political upheaval surrounding the Vietnam War. My political activism taught
      me to be wary of the potential misuses of scientific knowledge and to promote the
      positive applications of science for the benefit of society. I chose agricultural
      science for my postdoctoral work. Because I was not trained as a plant biologist,
      I devised a postdoctoral project that took advantage of my microbiological
      training, and I explored using genetic technologies to transfer the ability to
      fix nitrogen from prokaryotic nitrogen-fixing species to the model plant
      Arabidopsis thaliana with the ultimate goal of engineering crop plants. The
      invention of recombinant DNA technology greatly facilitated the cloning and
      manipulation of bacterial nitrogen-fixation ( nif) genes, but it also forced me
      to consider how much genetic engineering of organisms, including human beings, is
      acceptable. My laboratory has additionally studied host-pathogen interactions
      using Arabidopsis and the nematode Caenorhabditis elegans as model hosts.

PMID- 30192639
TI  - Hospitalization rate of paroxysmal supraventricular tachycardia in Sweden.
AB  - INTRODUCTION: The hospitalization rate of paroxysmal supraventricular tachycardia
      (PSVT) in a nationwide study is not established. We determined age- and sex
      specific hospitalization rates and time trends for hospitalized PSVT in the
      Swedish population between 1987 and 2010. METHODS: This nationwide study is based
      on the Swedish Hospital Discharge Register. The patients with first PSVT
      diagnoses between January 1987 and December 2010 were identified. RESULTS: A
      total of 42,765 individuals with PSVT were diagnosed (mean age 60 years; 44%
      males). The overall age- and sex-adjusted hospitalization rate was 20 per 100,000
      person-years. The hospitalization rate increased with advancing age with highest
      hospitalization rates in individuals aged 80-84 years (67.12 per 100,000 person
      years) and did not change significantly over time. A total of 20,011 (46.8%)
      patients had "lone" PSVT without any comorbidities. Lone PSVT patients were
      younger than PSVT patients with comorbidities (mean age 54 vs. 67 years, p =
      .0002). CONCLUSIONS: This study showed a slight preponderance for females and
      stable hospitalization rate of PSVT over time; the hospitalization rate increased
      with age. A high proportion of PSVT patients had no comorbidities. They were
      affected at a younger age than patients with comorbidities, which suggests an
      inherent predisposition. Key messages This study represents the first extensive
      and nationwide hospitalization study of PSVT. Hospitalization is highest in old
      age but a bimodal pattern was observed with a small peak in the first years of
      life. Patients with lone PSVT are younger than those with comorbidities; which
      suggests an inherent predisposition.

PMID- 30192640
TI  - Prenatal Steroids and Metabolic Dysfunction: Lessons from Sheep.
AB  - Prenatal exposure to excess steroids or steroid mimics can disrupt the normal
      developmental trajectory of organ systems, culminating in adult disease. The
      metabolic system is particularly susceptible to the deleterious effects of
      prenatal steroid excess. Studies in sheep demonstrate that prenatal exposure to
      excess native steroids or endocrine-disrupting chemicals with steroidogenic
      activity, such as bisphenol A, results in postnatal development of numerous
      cardiometabolic perturbations, including insulin resistance, increased adiposity,
      altered adipocyte size and distribution, and hypertension. The similarities in
      the phenotypic outcomes programmed by these different prenatal insults suggest
      that common mechanisms may be involved, and these may include hormonal imbalances
      (e.g., hyperandrogenism and hyperinsulinemia), oxidative stress, inflammation,
      lipotoxicity, and epigenetic alterations. Animal models, including the sheep,
      provide mechanistic insight into the metabolic repercussions associated with
      prenatal steroid exposure and represent valuable research tools in understanding
      human health and disease. Focusing on the sheep model, this review summarizes the
      cardiometabolic perturbations programmed by prenatal exposure to different native
      steroids and steroid mimics and discusses the potential mechanisms underlying the
      development of adverse outcomes. Expected final online publication date for the
      Annual Review of Animal Biosciences Volume 7 is February 15, 2019. Please see
      http://www.annualreviews.org/page/journal/pubdates for revised estimates.

PMID- 30192638
TI  - Anti-IL5 in Mild Asthma Alters Rhinovirus-Induced Macrophage, B Cell and
      Neutrophil Responses (MATERIAL): A Placebo-Controlled, Double-Blind Study.
AB  - RATIONALE: Eosinophils drive pathophysiology in stable and exacerbating
      eosinophilic asthma and therefore treatment is focused on the reduction of
      eosinophil numbers. Mepolizumab, a humanized monoclonal antibody that neutralizes
      interleukin (IL)-5 and efficiently attenuates eosinophils, proved clinically
      effective in severe eosinophilic asthma but not in mild asthma. OBJECTIVES: Study
      the effect of Mepolizumab on virus-induced immune responses in mild asthma.
      METHODS: Mild asthma patients, steroid-naive and randomized for eosinophil
      numbers, received 750 mg Mepolizumab iv in a placebo-controlled double-blind
      trial, 2 weeks after which patients were challenged with rhinovirus(RV)16. FEV1,
      FVC, FeNO, symptom scores (ACQ), viral load (PCR), eosinophil numbers, humoral
      (luminex, ELISA) and cellular (flow cytometry) immune parameters in blood, BALF
      and sputum, before and after Mepolizumab and RV16, were assessed. MEASUREMENTS
      AND MAIN RESULTS: Mepolizumab attenuated baseline blood eosinophils and their
      activation, attenuated trend wise sputum eosinophils and enhanced circulating NK
      cells. Mepolizumab did not affect FEV1, FVC and FeNO, neither at baseline nor
      after RV16. Upon RV16 challenge Mepolizumab did not prevent eosinophil
      activation, enhanced local B-lymphocytes and macrophages and reduced neutrophils
      and their activation. Mepolizumab also enhanced sIgA and reduced tryptase in
      BALF. Finally, Mepolizumab affected particularly RV16-induced MIP-3a, VEGF-A and
      IL-1RA production in BALF. CONCLUSION: Mepolizumab failed to prevent activation
      of remaining eosinophils and changed RV16-induced immune responses in mild
      asthma. Although these latter effects likely are due to attenuated eosinophil
      numbers, we cannot exclude a role for basophils. Clinical trial registration
      available at www.clinicaltrials.gov, ID NCT01520051.

PMID- 30192641
TI  - Discretionary Surgery: A Comparison of Workers' Compensation and Commercial
      Insurance.
AB  - BACKGROUND: Workers' compensation is intended for injuries that occur at work and
      is expected to be mostly for trauma and mostly nondiscretionary conditions. We
      tested the null hypothesis that there is no difference in the ratio of likely
      discretionary to likely nondiscretionary surgery between patients treated under
      workers' compensation compared with commercial insurance controlling for age,
      sex, and anatomical site for either traumatic or nontraumatic diagnoses. METHODS:
      Using claims data from the Texas workers' compensation database and Truven Health
      commercial claims we classified International Statistical Classification of
      Diseases and Related Health Problems, Ninth Revision, Clinical Modification (ICD
      9-CM) diagnoses and procedure codes as likely discretionary or likely
      nondiscretionary, and as traumatic or nontraumatic. Ratios of likely
      discretionary to likely nondiscretionary surgery were calculated and compared.
      RESULTS: Among patients treated under workers' compensation, the ratio of likely
      discretionary to likely nondiscretionary surgery was significantly higher for
      traumatic diagnoses (0.57 [95% confidence interval, CI, = 0.56-0.61] vs 0.38 [95%
      CI = 0.37-0.40], P < .05) and significantly lower for nontraumatic diagnoses (9.4
      [95% CI = 9.20-9.42] vs 13.2 [95% CI = 12.9-13.3], P < .05) compared with
      commercial insurance. CONCLUSIONS: Workers' compensation often covers likely
      discretionary musculoskeletal surgery, and insurance type may influence
      treatment.

PMID- 30192642
TI  - Incidence and Risk Factors of Symptomatic Venous Thromboembolism Following Foot
      and Ankle Surgery.
AB  - BACKGROUND: The incidence rate of venous thrombotic events (VTEs) following foot
      and ankle surgery is low. Currently, there is no consensus regarding
      postoperative prophylaxis or evidence to support risk stratification. METHODS: A
      2-part study assessing the incidence and factors for the development of VTE was
      conducted: (1) a retrospective observational cohort study of 22 486 adults to
      calculate the overall incidence following foot and/or ankle surgery from January
      2008 to May 2011 and (2) a retrospective matched case-control study to identify
      risk factors for development of VTE postsurgery. One control per VTE case matched
      on age and sex was randomly selected from the remaining patients. RESULTS: The
      overall incidence of VTE was 0.9%. Predictive risk factors in bivariate analyses
      included obesity, history of VTE, history of trauma, use of hormonal replacement
      or oral contraception therapy, anatomic location of surgery, procedure duration
      60 minutes or more, general anesthesia, postoperative nonweightbearing
      immobilization greater than 2 weeks, and use of anticoagulation. When significant
      variables from bivariate analyses were placed into the multivariable regression
      model, 4 remained statistically significant: adjusted odds ratio (aOR) for
      obesity, 6.1; history of VTE, 15.7; use of hormone replacement therapy, 8.9; and
      postoperative nonweightbearing immobilization greater than 2 weeks, 9.0. The risk
      of VTE increased significantly with 3 or more risk factors ( P = .001).
      CONCLUSION: The overall low incidence of VTE following foot and ankle surgery
      does not support routine prophylaxis for all patients. Among patients with 3 or
      more risk factors, the use of chemoprophylaxis may be warranted. LEVEL OF
      EVIDENCE: Level III, retrospective case series.

PMID- 30192644
TI  - Organ Function Assessment, Prevention, and Outcomes in Critically Ill Patients
      with Sepsis.

PMID- 30192643
TI  - Smoking and hypertension: Effect of adenosine deaminase polymorphism.
AB  - Adenosine modulates cardiovascular functions reducing blood pressure and heart
      rate. Adenosine deaminase (ADA) by the irreversible deamination of adenosine to
      inosine contributes to the regulation of adenosine concentration in body fluids.
      We have studied the interaction between smoking and ADA genetic variability
      concerning their effects on blood pressure. We have studied 344 subjects admitted
      to the hospital for cardiovascular diseases. The genotypes of two polymorphic
      loci within the ADA gene were determined: ADA1 and ADA2. Both loci show two
      alleles: ADA1*1 and ADA1*2 in ADA1 locus and ADA2*1 and ADA2*2 in ADA2 locus. In
      the absence of smoking, the proportion of subjects with hypertension tends to be
      lower in carriers of the ADA1*2 allele. In smoking subjects, the pattern is
      reversed and the proportion of those with hypertension tends to be higher in
      carriers of the ADA1*2 allele. A similar pattern is observed for ADA2 locus.
      Smoking increases the proportion of subjects showing hypertension: such effect is
      more marked in those carrying the ADA1*2 allele as compared to subjects with
      ADA1*1/*1 genotype. The same pattern of association is observed for ADA2 locus.
      The two loci show an additive effect. The odds ratio for hypertension in smokers
      vs nonsmokers is 1.450 in subjects carrying ADA1*1/*1 and ADA2*1/*1 genotypes,
      while it is 11.200 in subjects carrying the *2 alleles in both loci. From a
      practical point, a view of our results suggest that smokers carrying both ADA1*2
      and ADA2*2 alleles have a higher risk of hypertension.

PMID- 30192645
TI  - Pitavastatin ameliorates myocardial damage by preventing inflammation and
      collagen deposition via reduced free radical generation in isoproterenol-induced
      cardiomyopathy.
AB  - Pitavastatin inhibits 3 hydroxy 3 methyl glutaryl coenzyme A (HMGCoA) reductase
      enzyme, preventing cholesterol synthesis along with elevating high density
      apolipoprotein A1 (Apo-A1). The present study was designed to evaluate
      cardioprotective potential of pitavastatin at 1 mg/kg/day and 3 mg/kg/day dose
      for 14 days in low dose isoproterenol (ISO) (5 mg/kg/day for 7 consecutive days)
      induced myocardial damage. ISO administration induced significant reduction in
      endogenous antioxidant enzymes like reduced glutathione (GSH), superoxide
      dismutase (SOD), catalase (CAT) and raised thiobarbituric acid reactive
      substances (TBARS) indicating activated lipid peroxidation. Along with this, a
      significant increase in level of cardiac injury biomarkers vie, creatine kinase
      (CK-MB), lactate dehydrogenase (LDH), aspartate amino transferase (AST), tumor
      necrosis factor (TNF-alpha) and transforming growth factor (TGF-beta) as well as
      brain natriuretic peptide (BNP). Histological examination also revealed marked
      myocardial tissue damage in ISO treated rats. However, pretreatment with
      pitavastatin (3 mg/kg/day) significantly maintained nearly normal levels of
      cardiac biomarkers and oxidant antioxidant status as well as lipid peroxidation
      in ISO induced MI rats. Cardiac histological assessment and infarct size
      assessment also showed marked reduction in myocardial architecture alteration
      including infarct size as well as collagen deposition by pitavastatin that
      strongly supported biochemical findings. These observations strongly corroborate
      that pitavastatin prevents myocardial damages via up regulation of endogenous
      oxidants along with its hypocholesterolemic activity.

PMID- 30192646
TI  - Niacin prevents mitochondrial oxidative stress caused by sub-chronic exposure to
      methylmercury.
AB  - Humans and animals can be exposed to different chemical forms of mercury (Hg) in
      the environment. For example, methylmercury (MeHg)-contaminated fish is part of
      the basic diet of the riparian population in the Brazilian Amazon Basin, which
      leads to high total blood and plasma Hg levels in people living therein. Hg
      induces toxic effects mainly through oxidative stress. Different compounds have
      been used to prevent the damage caused by MeHg-induced reactive oxygen species
      (ROS). This study aims to investigate the in vivo effects of sub-chronic exposure
      to low MeHg levels on the mitochondrial oxidative status and to evaluate the
      niacin protective effect against MeHg-induced oxidative stress. For this purpose,
      Male Wistar rats were divided into four groups: control group, treated with
      drinking water on a daily basis; group exposed to MeHg at a dose of 100
      ug/kg/day; group that received niacin at a dose of 50 mg/kg/day in drinking
      water, with drinking water being administered by gavage; group that received
      niacin at a dose of 50 mg/kg/day in drinking water as well as MeHg at a dose of
      100 ug/kg/day. After 12 weeks, the rats, which weighed 500-550 g, were
      sacrificed, and their liver mitochondria were isolated by standard differential
      centrifugation. Sub-chronic exposure to MeHg (100 ug/kg/day for 12 weeks) led to
      mitochondrial swelling (p < 0.05) and induced ROS overproduction as determined by
      increased DFCH oxidation (p < 0.05), increased gluthatione oxidation (p < 0.05),
      and reduced protein thiol content (p < 0.05). In contrast, niacin supplementation
      inhibited oxidative stress, which counteracted and minimized the toxic MeHg
      effects on mitochondria.

PMID- 30192648
TI  - A Comparison of Locking Plates and Intramedullary Pinning for Fixation of
      Metacarpal Shaft Fractures.
AB  - BACKGROUND: Metacarpal shaft fractures that necessitate surgery are frequently
      fixated with either intramedullary pins or plates and screws. This study compared
      outcome measurements of these two techniques. METHODS: Patients operated on for
      closed shaft fractures of metacarpals 2-5 were examined at least 1 year after
      injury. All fractures were fixated by pinning between years 2013 and 2015 and by
      locking plates and screws between 2016 and 2017. Evaluation included range of
      motion measurements for all fingers compared with the contralateral hand;
      comparison of grip strength; finger alignment and rotation; Disabilities of the
      Arm, Shoulder and Hand (DASH) score; and radiographic measurements of fracture
      reduction and healing. RESULTS: Thirty patients with 39 fractured metacarpals
      treated by pinning were compared with 29 patients with 35 fractured metacarpals
      treated by locking plate and screws. Both groups had similar characteristics and
      preoperative fracture patterns on radiograph. Patients in the plate group were
      found to have significantly improved outcomes in total range of motion of the
      operated digits (loss of 4 degrees  extension, 10 degrees  flexion, and 14
      degrees  total vs 10 degrees  extension, 19 degrees  flexion, and 29 degrees 
      total), grip strength (93% vs 83% of contralateral hand), rotational deformity (5
      digits, 1 degrees  vs 15 digits, 6 degrees ), and DASH score (10.5 vs 15.6).
      Radiographic bone healing time (59 vs 50 days) and operative time (58 vs 41
      minutes) were both significantly longer in fractures fixated by plates.
      CONCLUSIONS: Fixation with locking plates allows earlier mobilization without
      need for splinting. Our study supports the use of this method over intramedullary
      pinning for metacarpal shaft fractures.

PMID- 30192647
TI  - Digital Video Laryngoscopy and Flexible Endoscopic Biopsies as an Alternative
      Diagnostic Workup in Laryngopharyngeal Cancer: A Prospective Clinical Study.
AB  - OBJECTIVES: An office-based workup strategy for patients with laryngopharyngeal
      lesions suspicious for carcinoma is analyzed. The feasibility of office-based
      transnasal flexible endoscopic biopsies under local anesthesia and the impact on
      the diagnostic workup are evaluated. METHODS: This study is a prospective
      analysis of patients with laryngeal, oropharyngeal, and hypopharyngeal lesions
      suspicious for carcinoma. One hundred eighty-eight participants were divided into
      2 groups. The first group underwent an office-based biopsy procedure under local
      anesthesia using a flexible digital video laryngoscope with instrument channel (n
      = 53), and the second group underwent a biopsy procedure under general anesthesia
      using rigid laryngopharyngoscopy (n = 135). RESULTS: Office-based flexible
      endoscopic biopsies were tolerated well, and there were no complications. These
      biopsies were 92.5% successful in acquiring a definitive diagnosis. Costs were
      reduced. Diagnostic workup time and time until start of therapy were reduced to 2
      days and 27 days, respectively. CONCLUSION: Office-based biopsy under local
      anesthesia using flexible digital video laryngoscopy is safe, cost-effective, and
      successful in providing a histopathological diagnosis. It reduces the diagnostic
      workup time significantly in patients with laryngeal, oropharyngeal, and
      hypopharyngeal cancer, while also reducing the necessity to subsequently perform
      a rigid laryngopharyngoscopy under general anesthesia.

PMID- 30192649
TI  - Yield and Efficiency of Novel Intensified Tuberculosis Case-Finding Algorithms
      for People Living with HIV.
AB  - : Rationale/Objectives: The recommended tuberculosis (TB) intensified case
      finding (ICF) algorithm for people living with HIV (PLHIV) - symptom-based
      screening followed by Xpert MTB/RIF (Xpert) testing - is insufficiently sensitive
      and results in unnecessary Xpert testing. We evaluated whether novel ICF
      algorithms combining C-reactive protein (CRP)-based screening with urine
      Determine TB-LAM (TB-LAM), sputum Xpert and/or culture could improve ICF yield
      and efficiency. Methods/Measurements: We compared the yield and efficiency of
      novel ICF algorithms inclusive of POC CRP-based TB screening and confirmatory
      testing with urine TB-LAM (if CD4 count <=100 cells/MUL), sputum Xpert, and/or a
      single sputum culture among consecutive PLHIV with CD4 counts <=350 cells/uL
      initiating antiretroviral therapy in Uganda. MAIN RESULTS: Of 1245 PLHIV, 203
      (16%) had culture-confirmed TB including 101 (49%) patients with CD4 counts <=100
      cells/MUL. Compared to the current ICF algorithm, POC CRP-based screening
      followed by Xpert testing had similar yield (56% [95% CI: 49-63] vs. 59% [95% CI:
      51-65]) but consumed less than half as many Xpert assays per TB case detected (9
      vs. 4). Addition of TB-LAM did not significantly increase diagnostic yield
      relative to the current ICF algorithm but provided same-day diagnosis for 26% of
      TB patients with advanced HIV. Addition of a single culture to TB-LAM and Xpert
      substantially improved ICF yield, identifying 78% of all TB cases. CONCLUSIONS:
      POC CRP-based screening can improve ICF efficiency among PLHIV. Addition of TB
      LAM and a single culture to Xpert confirmatory testing could enable HIV programs
      to increase the speed of TB diagnosis and ICF yield.

PMID- 30192650
TI  - Amiodarone induces epithelial-mesenchymal transition in A549 cells via activation
      of TGF-beta1.
AB  - Amiodarone is a high effectiveness anti-arrhythmia agent which is able to induce
      pulmonary fibrosis. Many studies have shown that the epithelial-mesenchymal
      transition (EMT) was a significant process in pulmonary fibrosis. So far, there
      are no studies about whether EMT was associated with amiodarone-induced pulmonary
      fibrosis, which was therefore explored in this study. In addition, the underlying
      mechanisms of amiodarone-induced pulmonary fibrosis were examined in vitro. We
      found the EMT marker (alpha-SMA) was significantly increased, while the E
      cadherin was significantly decreased in adenocarcinomic human alveolar basal
      epithelial cells (A549) after amiodarone treatment, suggesting that the
      epithelial cells were an important source of mesenchymal cells. Transforming
      growth factor beta1 (TGF-beta1) was also increased significantly after amiodarone
      treatment. In conclusion, this study suggested amiodarone could induce pulmonary
      fibrosis via EMT, and the TGF-beta1 may be a key profibrotic cytokine in
      mechanisms of amiodarone-induced pulmonary fibrosis.

PMID- 30192651
TI  - Aphtha Major Perianalis.

PMID- 30192652
TI  - Associations of genetic polymorphisms of the vitamin D pathway with blood
      pressure in a Han Chinese population.
AB  - Vitamin D deficiency can lead to high blood pressure. Polymorphisms in the
      vitamin D hydroxylase gene have been associated with serum vitamin D levels in
      some Western countries. The aim of this study was to investigate whether
      polymorphisms of hydroxylase genes in the vitamin D metabolic pathway contribute
      to hypertension by affecting serum vitamin D status in a Han Chinese population.
      We selected four single nucleotide polymorphisms (SNPs; rs1993116 and rs10741657
      of CYP2R1; rs4809957 and rs6068816 of CYP24A1) for genotyping in 525 control
      subjects and 324 hypertensive patients, and detected vitamin D levels in blood in
      subsets of these groups. The results showed that rs1993116 and rs10741657 were
      associated with a reduced risk of hypertension. The odds ratios, 95% confidence
      intervals, and p values from the adjusted additive and dominant models were 0.788
      (0.644-0.963, p = 0.02) and 0.719 (0.545-0.949, p = 0.02) for rs1993116 and 0.805
      (0.66-0.983, p = 0.033) and 0.733 (0.556-0.966, p = 0.028) for rs10741657. A
      protective effect of CYP2R1 with regard to hypertension was also found in males
      and non-smokers. The TT genotypes of rs1993116 and rs10741657 were associated
      with significantly lower systolic blood pressure in treated hypertensive patients
      (both p = 0.002). No association with hypertension was found for the two SNPs of
      CYP24A1, and no difference in vitamin D level was found among the three genotypes
      of the four SNPs. Our results suggest that CYP2R1 polymorphisms are associated
      with a reduced risk of hypertension independent of the vitamin D level in the Han
      Chinese population.

PMID- 30192653
TI  - Inhibition of Suicidal Erythrocyte Death by Chronic Hypoxia.
AB  - : Tang, Feng, Lin Feng, Runle Li, Wei Wang, Huihui Liu, Quanyu Yang, and Ri-Li
      Ge. Inhibition of suicidal erythrocyte death by chronic hypoxia. High Alt Med
      Biol. 00:000-000, 2018. BACKGROUND/AIMS: High-altitude polycythemia is defined by
      the increase of hematocrit and hemoglobin at high altitudes caused by production
      of excessive erythrocytes. Eryptosis is a process by which mature erythrocytes
      undergo self-destruction sharing several features with apoptosis. However, the
      eryptosis in high-altitude hypobaric hypoxia is unknown. Thus, the main purpose
      of this study was to investigate whether chronic hypoxia affected eryptosis and,
      if so, by what mechanisms. METHODS: Biotin labeling technology was utilized to
      study the survival of red blood cells in chronic hypoxia. Flow cytometry was used
      to determine the volume of mature erythrocytes from forward scatter,
      phosphatidylserine scrambling from annexin-V-binding, intracellular Ca2+ from
      Fluo-3-AM, reactive oxygen species (ROS) abundance from ROS-probe, and ceramide
      and CD47 abundance utilizing specific antibodies. RESULTS: The volume of mature
      erythrocytes was significantly changed, and the percentage of annexin-V-binding
      cells was significantly decreased under chronic hypobaric hypoxia. Erythrocyte
      survival was improved under chronic hypoxia, and chronic hypoxia resulted in a
      decrease in intracellular Ca2+ in vivo and influenced eryptosis which was induced
      by the Ca2+-ionophore ionomycin (1 MUM, 60 minutes) in vitro. Chronic hypoxia
      also resulted in an increase in CD47 and ceramide abundance, but it had no effect
      on ROS formation. CONCLUSIONS: Chronic hypobaric hypoxia can inhibit eryptosis by
      decreasing intracellular Ca2+ and increasing integrin-associated protein CD47.

PMID- 30192654
TI  - Dexamethasone decreases the autotaxin-lysophosphatidate-inflammatory axis in
      adipose tissue: implications for the metabolic syndrome and breast cancer.
AB  - Lysophosphatidate (LPA) signaling through 6 receptors is regulated by the balance
      of LPA production by autotaxin (ATX) vs. LPA degradation by lipid phosphate
      phosphatases (LPPs). LPA promotes an inflammatory cycle by increasing the
      synthesis of cyclooxygenase-2 and multiple inflammatory cytokines that stimulate
      further ATX production. We aimed to determine whether the anti-inflammatory
      glucocorticoid (GC) dexamethasone (Dex) functions partly by decreasing the ATX
      LPA inflammatory cycle in adipose tissue, a major site of ATX secretion.
      Treatment of human adipose tissue with 10-1000 nM Dex decreased ATX secretion,
      increased LPP1 expression, and decreased mRNA expressions of IL-6, TNF-alpha,
      peroxisome proliferator-activated receptor (PPAR)-gamma, and adiponectin.
      Cotreatment with rosiglitazone (an insulin sensitizer), insulin, or both
      abolished Dex-induced decreases in ATX and adiponectin secretion, but did not
      reverse Dex-induced decreases in secretions of 20 inflammatory cytokines and
      chemokines. Dex-treated mice exhibited lower ATX activity in plasma, brain, and
      adipose tissue; decreased mRNA levels for LPA and sphingosine 1-phosphate (S1P)
      receptors in brain; and decreased plasma concentrations of LPA and S1P. Our
      results establish a novel mechanism for the anti-inflammatory effects of Dex
      through decreased signaling by the ATX-LPA-inflammatory axis. The GC action in
      adipose tissue has implications for the pathogenesis of insulin resistance and
      obesity in metabolic syndrome and breast cancer treatment.-Meng, G., Tang, X.,
      Yang, Z., Zhao, Y., Curtis, J. M., McMullen, T. P. W., Brindley, D. N.
      Dexamethasone decreases the autotaxin-lysophosphatidate-inflammatory axis in
      adipose tissue: implications for the metabolic syndrome and breast cancer.

PMID- 30192655
TI  - A pilot clinical trial of a near-infrared laser vaccine adjuvant: safety,
      tolerability, and cutaneous immune cell trafficking.
AB  - Many vaccines require adjuvants to enhance immunogenicity, but there are few safe
      and effective intradermal (i.d.) adjuvants. Murine studies have validated the
      potency of laser illumination of skin as an adjuvant for i.d. vaccination with
      advantages over traditional adjuvants. We report a pilot clinical trial of low
      power, continuous-wave, near-infrared laser adjuvant treatment, representing the
      first human trial of the safety, tolerability, and cutaneous immune cell
      trafficking changes produced by the laser adjuvant. In this trial we demonstrated
      a maximum tolerable energy dose of 300 J/cm2 to a spot on the lower back. The
      irradiated spot was biopsied 4 h later, as was a control spot. Paired biopsies
      were submitted for histomorphologic and immunohistochemical evaluation in a
      blinded fashion as well as quantitative PCR analysis for chemokines and
      cytokines. Similar to prior murine studies, highly significant reductions in
      CD1a+ Langerhans cells in the dermis and CD11c+ dermal dendritic cells were
      observed, corresponding to the increased migratory activity of these cells;
      changes in the epidermis were not significant. There was no evidence of skin
      damage. The laser adjuvant is a safe, well-tolerated adjuvant for i.d.
      vaccination in humans and results in significant cutaneous immune cell
      trafficking.-Gelfand, J. A., Nazarian, R. M., Kashiwagi, S., Brauns, T., Martin,
      B., Kimizuka, Y., Korek, S., Botvinick, E., Elkins, K., Thomas, L., Locascio, J.,
      Parry, B., Kelly, K. M., Poznansky, M. C. A pilot clinical trial of a near
      infrared laser vaccine adjuvant: safety, tolerability, and cutaneous immune cell
      trafficking.

PMID- 30192657
TI  - Timely Antiviral Administration During an Influenza Pandemic: Key Components.
AB  - Prompt treatment of ill persons with influenza antivirals will be an important
      part of a future pandemic influenza response. This essay reviews key lessons
      learned from the 2009 H1N1 pandemic and the changing landscape of antiviral drug
      availability, and identifies and describes the multiple components needed to
      ensure the timely administration of antiviral drugs during a future pandemic.
      Fortunately, many of these planning efforts can take place before a pandemic
      strikes to improve outcomes during a future public health emergency.

PMID- 30192656
TI  - Use of Medical Countermeasures in Small-Scale Emergency Responses.
AB  - It is well documented that long-standing focus on public health emergency
      preparedness medical countermeasures (MCMs) distribution and mass dispensing
      capabilities for mitigation of bioterrorism incidents and a lack of real-world
      opportunities to test national preparedness for large-scale emergencies has
      hindered development of a body of evidence-based practices in the United States.
      To encourage jurisdictions seeking innovative opportunities for continuous
      improvement, we describe instances when the MCM capabilities were used to address
      smaller-scale, more-frequent public health emergencies such as disease outbreaks,
      natural disasters, or routine influenza vaccination. We argue that small-scale
      events represent a critical opportunity that state, local, tribal, and
      territorial entities can utilize for greater gains in MCM operational readiness
      than through exercises or planned reviews. By using and evaluating MCM
      capabilities during a real response, jurisdictions can advance preparedness
      science and support the translation of research into practice, thereby increasing
      their capacity to scale up for larger, rarer, higher-consequence emergencies.

PMID- 30192658
TI  - Contraception as a Medical Countermeasure to Reduce Adverse Outcomes Associated
      With Zika Virus Infection in Puerto Rico: The Zika Contraception Access Network
      Program.
AB  - The Zika Contraception Access Network established a network of 153 physicians
      across Puerto Rico as a short-term emergency response during the 2016-2017 Zika
      virus outbreak to provide client-centered contraceptive counseling and same-day
      contraception services at no cost for women who chose to prevent pregnancy.
      Between May 2016 and August 2017, 21 124 women received services. Contraception
      was used as a medical countermeasure to reduce adverse Zika-related reproductive
      outcomes during the outbreak and may be considered a key strategy in other
      emergencies.

PMID- 30192659
TI  - Monitoring and Assessment of Medical Countermeasures as Part of a Public Health
      Emergency Response.

PMID- 30192660
TI  - Medical Countermeasures: A Stitch in Time Saves Nine.

PMID- 30192661
TI  - Serosurveillance of First-Year Military Personnel for Hepatitis A and B.

PMID- 30192662
TI  - Disaster Response 2.0: Noncommunicable Disease Essential Needs Still Unmet.

PMID- 30192663
TI  - Taiwan's Annual Seasonal Influenza Mass Vaccination Program-Lessons for Pandemic
      Planning.
AB  - Rapid medical countermeasure (MCM) dispensing is an important intervention during
      a public health emergency. In the United States, MCM planning and exercising
      efforts have largely focused on dispensing therapeutics, with less emphasis on
      mass vaccination operations that would require additional specialized staff and
      infrastructure. Difficulties in distributing vaccines during the 2009 H1N1
      influenza pandemic highlighted the need for enhanced planning and exercising of
      plans for conducting mass vaccination campaigns. In Taiwan, seasonal influenza
      mass vaccination campaigns are conducted annually, which both mitigate the
      effects of seasonal influenza and serve as functional exercises for mass
      vaccination operations during a pandemic. To identify lessons that can be applied
      to mass vaccination planning in the United States and elsewhere, we conducted an
      in-person observation and data review of Taiwan's annual seasonal influenza mass
      vaccination efforts in October 2017. We offer findings and recommendations for
      enhancing preparedness for seasonal and pandemic influenza and other public
      health emergencies that would require mass vaccination.

PMID- 30192664
TI  - Political Will, Coordination, and Planning: Key Components for Strengthening
      National Response to Public Health Emergencies and Disasters in Latin America and
      the Caribbean Countries.

PMID- 30192665
TI  - Education of Elderly Patients About Emergency Preparedness by Health Care
      Practitioners.

PMID- 30192667
TI  - Public Health Emergencies: Unpacking Medical Countermeasures Management for
      Preparedness and Response Introduction and Contents of the Volume.

PMID- 30192666
TI  - Medical Countermeasure Actions-A Historical Perspective.

PMID- 30192668
TI  - Planning Considerations for State, Local, Tribal, and Territorial Partners to
      Receive Medical Countermeasures From CDC's Strategic National Stockpile During a
      Public Health Emergency.
AB  - The Centers for Disease Control and Prevention's Strategic National Stockpile is
      a national repository of potentially life-saving medical countermeasures
      including pharmaceuticals and medical supplies for use in a public health
      emergency severe enough to cause local, regional, and state supplies to run out.
      Several planning considerations can assist state, local, tribal, and territorial
      jurisdictions in preparing to receive, distribute, dispense, and administer
      medical countermeasures from the Strategic National Stockpile. These
      considerations include, but are not limited to, issues surrounding regulatory
      requirements, controlled substances, cold chain management, and ancillary supply
      needs. Multiple aspects to consider for each of these functions are discussed
      here to assist partners in their planning efforts.

PMID- 30192669
TI  - Key Elements for Conducting Vaccination Exercises for Pandemic Influenza
      Preparedness.

PMID- 30192670
TI  - Public Health Emergency Response Lessons Learned by Rapid Deployment Force 3,
      2006-2016.
AB  - Following Hurricane Katrina, the uniformed US Public Health Service created an
      updated system through which its officers participated in emergency responses.
      The Rapid Deployment Force (RDF) concept, begun in 2006, involved five teams of
      officers with diverse clinical and public health skill sets organized into an
      incident command system led by a team commander. Each team can deploy within 12
      hours, according to a defined but flexible schedule. The core RDF mission is to
      set up and provide care for up to 250 patients, primarily persons with chronic
      diseases or disabilities, in a temporary federal medical station. Between 2006
      and 2016, the RDF 3 team deployed multiple times in response to natural disasters
      and public health emergencies. Notable responses included Hurricane Sandy in
      2012, the unaccompanied children mission in 2014, and the Louisiana floods in
      2016. Lessons learned from the RDF 3 experience include the need for both
      clinical and public health capacity, the value of having special mental health
      resources, the benefits of collaboration with other federal medical responders,
      and recognition of the large burden of chronic disease management issues
      following natural disasters.

PMID- 30192672
TI  - Medical Countermeasures: Mission, Method, and Management.

PMID- 30192671
TI  - Performance of Point of Dispensing Setup Drills for Distribution of Medical
      Countermeasures: United States and Territories, 2012-2016.
AB  - OBJECTIVES: To describe results of points of dispensing (POD) medical
      countermeasure drill performance among local jurisdictions. METHODS: To compare
      POD setup times for each year, we calculated descriptive statistics of annual
      jurisdictional POD setup data submitted by over 400 local jurisdictions across 50
      states and 8 US territories to a Centers for Disease Control and Prevention (CDC)
      program monitoring database from July 2012 to June 2016. RESULTS: In data
      collected from July 2012 to June 2015, fewer than 5% of PODs required more than
      240 minutes to set up, although the proportion increased from July 2015 to June
      2016 to almost 12%. From July 2012 to June 2016, more than 60% of PODs were set
      up in less than 90 minutes, with 60 minutes as the median setup time during the
      period. CONCLUSIONS: Our results yield evidence of national progress for response
      to a mass medical emergency. Technical assistance may be required to aid certain
      jurisdictions for improvement. Public Health Implications. The results of this
      study may inform future target times for performance on POD setup activities and
      highlight jurisdictions in need of technical assistance.

PMID- 30192673
TI  - An Efficient Model for Designing Medical Countermeasure Just-in-Time Training
      During Public Health Emergencies.
AB  - Rapidly training numerous staff and volunteers to distribute and dispense medical
      countermeasures is challenging because of limited resources and evolving
      information during public health emergencies. The Applied Learning and
      Development Team within the Division of State and Local Readiness at the Centers
      for Disease Control and Prevention (CDC) proposes just-in-time training (JITT)
      templates that can be rapidly customized and implemented early in any public
      health emergency. The proposed template model aligns with modular training design
      research to increase relevance and rapid deployment of training. Two case studies
      are described to demonstrate the potential for training templates to support
      medical countermeasure responses: (1) customization and implementation of a JITT
      to prepare staff to work on a CDC task force during the 2016-2017 Zika virus
      response and (2) a new modular, customizable course to teach the basics about
      working at a point-of-dispensing site. Flexible JITT templates in these cases
      reduce the burden on emergency planners and trainers, allowing for rapidly
      developed, customized training viable for all emergency responses.

PMID- 30192674
TI  - Novel Continuous and Manual Sampling Methods for Beef Trim Microbiological
      Testing.
AB  - A sampling method that represents a greater proportion of the beef trimmings in a
      900-kg combo bin should improve the current pathogen sampling and detection
      programs used by fresh beef processors. This study compared two novel,
      nondestructive sampling methodologies (a continuous sampling device [CSD] and a
      manual sampling device [MSD]) with the current industry methodologies, the N60
      Excision (the "gold standard") and N60 Plus, for collection of trim samples.
      Depending on the experiment, samples were analyzed for naturally occurring
      Escherichia coli O157:H7 or Salmonella, inoculated surrogates, or indicator
      organisms in multiple plants, on multiple days, across multiple lean percentage
      mixtures. Experiments 1A and 1B with natural contamination found no E. coli
      O157:H7 but similar ( P > 0.05) prevalence of Salmonella (CSD 9.2% versus N60
      Excision 6.0%) and similar ( P > 0.05) levels of indicator organisms for CSD
      compared with both N60 methodologies. In experiments 2 and 3, CSD cloth sampling
      had the same or higher prevalence of naturally occurring E. coli O157:H7 and E.
      coli O157:H7 surrogate organisms, as well as similar levels of indicator
      organisms compared with the N60 methodologies. In experiment 4, MSD cloth
      sampling detected similar ( P > 0.05) prevalence of E. coli O157:H7 surrogate
      organisms, as well as slightly lower ( P < 0.05) levels of indicator organisms
      compared with N60 Plus. In experiment 5, the MSD found similar ( P > 0.05)
      prevalence of naturally occurring E. coli O157:H7 and the same or slightly higher
      ( P < 0.05) levels of naturally occurring indicator organisms compared with N60
      Plus. In experiment 6, the MSD detected the same ( P > 0.05) prevalence of
      naturally occurring Salmonella as did N60 Excision. The results of these
      experiments collectively demonstrate that sampling beef trim using either the CSD
      or MSD provides organism recovery that is similar to or better than the N60
      Excision or the N60 Plus methodologies.

PMID- 30192675
TI  - Metals in Mytillus galloprovincialis (Lamarck 1819) and Ensis directus (Conrad
      1883): Risk Assessment.
AB  - The study has been conducted with inductively coupled plasma optical emission
      spectrometry to determine the content of toxic heavy metals, macroelements, and
      essential elements in two species of bivalves of commercial interest in the
      Canary Islands: the Mediterranean mussel ( Mytillus galloprovincialis, Lamarck
      1819) and the razor clam ( Ensis directus, Conrad 1883). The study included 40
      samples corresponding to 20 specimens of each species acquired from fishmongers
      on the island of Tenerife. E. directus had higher levels of metals, except for B,
      Cd, Na, and Zn (0.98, 0.02, 2,006.93, and 15.07 mg/kg, respectively) compared
      with those in M. galloprovincialis, B, Cd, Na, and Zn (2.67, 0.12, 2,267.7, and
      22.27 mg/kg, respectively). In both bivalve molluscs, the maximum limits
      established by European legislation on food for human consumption were not
      exceeded. Likewise, the estimated daily intakes for the toxic metals Pb and Cd
      were below the admissible daily intakes.

PMID- 30192676
TI  - An Evaluation of the Hygiene Practices of European Street Food Vendors and a
      Preliminary Estimation of Food Safety for Consumers, Conducted in Paris.
AB  - The aim of this study was to evaluate hygiene conditions and practices in
      selected street food facilities in Paris, France. One hundred twenty mobile food
      establishments were studied: kiosks, 66 (55%); stands, 32 (26.7%); and food
      trucks, 22 (18.3%). Inspection of street food vendors and short interviews with
      staff using a specially designed checklist revealed that none of them were
      entirely hygienic. The hygiene conditions of the facilities themselves were the
      most satisfactory (77% of them were up to standard), but hygiene was less so for
      production and distribution processes (65% were satisfactory) and personal
      hygiene (67% were satisfactory). A significant ( P <= 0.05) correlation between
      the general hygiene status and the hygiene conditions of the production and
      distribution processes ( r = 0.86) and the hygiene practices of workers ( r =
      0.86) was found. The instances of noncompliance that were found may affect the
      safety of street-vended food. Because of its increasing popularity, it is
      important to correct poor hygiene practices. It is very important to identify
      common instances of noncompliance for street food facilities and to develop real
      remedial actions. Procedures to control the hygiene of street food vendors should
      also be developed. The checklist, which was specially designed to evaluate street
      vendor outlets, could also be used to pre-assess the hygiene conditions of
      production by those responsible for food hygiene. Furthermore, it could serve as
      a checklist for self-assessment (internal audit) by the vendors themselves and be
      adopted as a consumer education tool, to increase awareness of food hygiene of a
      catering facility.

PMID- 30192677
TI  - Letter to the Editor.

PMID- 30192678
TI  - Reply.

PMID- 30192680
TI  - Statistical Primer for Athletic Trainers: Understanding the Role of Statistical
      Power in Comparative Athletic Training Research.
AB  - OBJECTIVE:   To describe the concept of statistical power as related to
      comparative interventions and how various factors, including sample size, affect
      statistical power. BACKGROUND:   Having a sufficiently sized sample for a study
      is necessary for an investigation to demonstrate that an effective treatment is
      statistically superior. Many researchers fail to conduct and report a priori
      sample-size estimates, which then makes it difficult to interpret nonsignificant
      results and causes the clinician to question the planning of the research design.
      DESCRIPTION:   Statistical power is the probability of statistically detecting a
      treatment effect when one truly exists. The alpha level, a measure of differences
      between groups, the variability of the data, and the sample size all affect
      statistical power. RECOMMENDATIONS:   Authors should conduct and provide the
      results of a priori sample-size estimations in the literature. This will assist
      clinicians in determining whether the lack of a statistically significant
      treatment effect is due to an underpowered study or to a treatment's actually
      having no effect.

PMID- 30192683
TI  - Stress oxidative and genotoxicity in Prochilodus lineatus (Valenciennes, 1836)
      exposed to commercial formulation of insecticide cypermethrin.
AB  - The use of toxic pesticides has become a world problem because they can
      contaminate streams and rivers, producing an adverse impact on non-target aquatic
      biota, including fishes. Cypermethrin is one of the most important insecticides
      to control ectoparasites in wide-scale. The aim of this study was to evaluate the
      effect of commercial formulations of cypermethrin, SHERPA O (0.0, 0.075, 0.15,
      and 0.3 ug/L of cypermethrin) in fish Prochilodus lineatus for 96 h in semi
      static condition, using biomarkers of genotoxicity: micronucleus frequency (MNF)
      in erythrocytes and biomarkers of oxidative damage: lipid peroxidation (TBARS)
      and antioxidant defenses, catalase (CAT) and glutathione (GSH) in liver tissue.
      Our results showed a significant decrease (p < 0.05) of CAT at pesticide
      concentrations of 0.150 and 0.300 MUg/L, but no significant difference was
      observed in TBARS or GSH in any exposed group (p > 0.05) in comparison to the
      control. A significant increase was observed in the MNF in the group exposed to
      0.3 MUg/L of cypermethrin compared to negative control (p < 0.05). Finally, P.
      lineatus proved to be a sensitive species to the commercial formulations of
      cypermethrin and that CAT and MNF are effective indicators of these toxic
      effects.

PMID- 30192684
TI  - Innovations in EMS Education.

PMID- 30192685
TI  - Apoptotic effect of a phytosterol-ingredient and its main phytosterol (beta
      sitosterol) in human cancer cell lines.
AB  - Dietary interventions may effectively control cancer development, with
      phytosterols (PS) being a class of cancer chemopreventive dietary phytochemicals.
      The present study, for the first time, evaluates the antiproliferative effects of
      a PS-ingredient used for the enrichment of several foods and its main PS, beta
      sitosterol, at physiological serum levels, in the most prevalent cancer cells in
      women (breast (MCF-7), colon (HCT116) and cervical (HeLa)). In all three cell
      lines, these compounds induced significant cell viability reduction without a
      clear time- and dose-dependent response. Moreover, all treatments produced
      apoptotic cell death with the induction of DNA fragmentation through the
      appearance of a sub-G1 cell population. Thus, the use of PS as functional
      ingredients in the development of PS-enriched foods could exert a potential
      preventive effect against human breast, colon and cervical cancer, although
      further in vivo studies are required to confirm our preclinical findings.

PMID- 30192686
TI  - Consumer perceptions of using social media for health purposes: Benefits and
      drawbacks.
AB  - Consumers are increasingly using social media to interact with other consumers
      about health conditions and treatment options. This study aimed to investigate
      the advantages and disadvantages of using social media for health-related
      purposes from the consumers' perspectives. Five focus groups with 36 Australian
      adults with a chronic condition and on medication were conducted, audio-recorded,
      transcribed verbatim, and thematically analysed. Consumers reported that social
      media was very convenient, for accessing health-related information and for peer
      engagement; user-friendly; improved their health knowledge; empowered them; and
      provided social and emotional support. The disadvantages included information
      overload, wasting time; negative feelings; doubts about online information
      credibility; and issues related to online interactions. Despite some
      disadvantages, health-related use of social media led consumers to feel
      supported, knowledgeable, and empowered. Consumers' motivation to keep accessing
      social media for health-related purposes opens up avenues for the delivery of
      services via social media.

PMID- 30192681
TI  - Two 4-Week Balance-Training Programs for Chronic Ankle Instability.
AB  - CONTEXT:   Traditional single-limb balance (SLB) and progressive dynamic balance
      training programs for those with chronic ankle instability (CAI) have been
      evaluated in the literature. However, which training program may be more
      beneficial is not known. OBJECTIVE:   To investigate the effects of a progressive
      hop-to-stabilization balance (PHSB) program compared with an SLB program on self
      reported function, dynamic postural control, and joint position sense (JPS) where
      angle and direction were self-reported by participants with CAI. DESIGN:  
      Randomized controlled clinical trial. SETTING:   A single testing location in a
      mid-Atlantic state. PATIENTS OR OTHER PARTICIPANTS:   A total of 18 participants
      (age = 18.38 +/- 1.81 years; height = 175.26 +/- 6.64 cm; mass = 75.79 +/- 12.1
      kg) with CAI. INTERVENTION(S):   Participants were randomly assigned to the PHSB
      or SLB program. The PHSB and SLB groups pursued their 4-week programs 3 times a
      week. The PHSB group performed a battery of single-limb hop-to-stabilization
      exercises, while the SLB group performed a series of SLB exercises. Exercises
      were advanced throughout the 4 weeks for both groups. MAIN OUTCOMES MEASURE(S):  
      Pretest and posttest measurements were the Foot and Ankle Ability Measure (FAAM)
      Activities of Daily Living subscale; FAAM-Sports subscale; Star Excursion Balance
      Test in the anterior, posteromedial, and posterolateral directions; and weight
      bearing JPS blocks (dorsiflexion, plantar flexion, inversion, eversion). RESULTS:
      A significant main effect of time was present for the FAAM-Activities of Daily
      Living, FAAM-Sports, Star Excursion Balance Test (anterior, posteromedial, and
      posterolateral directions), and JPS (dorsiflexion, plantar flexion, inversion),
      as posttest results improved for the PHSB and SLB groups. The main effect of
      group was significant only for the FAAM-Sports, with the SLB group improving more
      than the PHSB group. CONCLUSIONS:   Either a 4-week PHSB or SLB can be used in
      athletes with CAI, as both programs resulted in similar gains.

PMID- 30192687
TI  - Feasibility of Out-of-Hospital Cardiac Arrest Ultrasound by EMS Physicians.
AB  - INTRODUCTION: Point-of-care ultrasound (POCUS) has been suggested as a useful
      tool to predict survival and guide interventions in out-of-hospital cardiac
      arrest (OHCA). While POCUS has been deployed in prehospital settings, a minimal
      amount of data exists on prehospital use, particularly by personnel with limited
      ultrasound experience. We aimed to characterize the feasibility and barriers to
      prehospital POCUS during OHCA by emergency medicine services (EMS) physicians in
      training. METHODS: We deployed the SonoSite iViz portable ultrasound device for
      use by EMS physicians for OHCA in an urban EMS system. All physicians received
      POCUS education as part of their graduate medical training and were provided an
      instructional video on use of the SonoSite iViz device. POCUS use was limited to
      identifying cardiac motion during pulse checks, without interrupting
      resuscitation, and the results could be used to supplement management at the
      physicians' discretion. Data were recorded prospectively by saving images on the
      device and through a custom electronic form within the patient care report. The
      primary measure was the frequency of use of POCUS during OHCA. Secondarily, we
      characterized agreement by expert (ultrasound fellowship trained) faculty (using
      a kappa statistic) and identified reported barriers to the use of prehospital
      POCUS. RESULTS: From November 2016 to March 2017, 348 physician field responses
      were reviewed, including 127 cases of OHCA. There were 106 patients remaining in
      arrest on physician arrival, with 56 (52.8%) cases of POCUS use. Still or video
      images were recorded in 48 cases; video in 34 cases. From video images, agreement
      in identifying cardiac motion between the EMS physician and expert reviewer
      occurred in 91% of cases (K = 0.82). Reasons cited for not using POCUS included
      return of circulation soon before or after arrival, prioritizing clinical
      interventions, not having the ultrasound device, mechanical failure, and
      cessation of resuscitation per advanced directives. CONCLUSION: Use of POCUS by
      EMS physicians to detect cardiac activity in OHCA is feasible and correlates with
      expert interpretation. Several avoidable barriers were identified and should be
      considered in the future implementation of prehospital POCUS. Larger studies are
      needed to determine what role POCUS may play in prehospital cardiac arrest
      management.

PMID- 30192688
TI  - Legal and ethical issues surrounding the use of crowdsourcing among healthcare
      providers.
AB  - As the pace of medical discovery widens the knowledge-to-practice gap,
      technologies that enable peer-to-peer crowdsourcing have become increasingly
      common. Crowdsourcing has the potential to help medical providers collaborate to
      solve patient-specific problems in real time. We recently conducted the first
      trial of a mobile, medical crowdsourcing application among healthcare providers
      in a university hospital setting. In addition to acknowledging the benefits, our
      participants also raised concerns regarding the potential negative consequences
      of this emerging technology. In this commentary, we consider the legal and
      ethical implications of the major findings identified in our previous trial
      including compliance with the Health Insurance Portability and Accountability
      Act, patient protections, healthcare provider liability, data collection, data
      retention, distracted doctoring, and multi-directional anonymous posting. We
      believe the commentary and recommendations raised here will provide a frame of
      reference for individual providers, provider groups, and institutions to explore
      the salient legal and ethical issues before they implement these systems into
      their workflow.

PMID- 30192690
TI  - Ocular Whipple Disease: Report of Three Cases.
AB  - PURPOSE: To emphasize the different manifestations of ocular involvement in
      Whipple disease with challenge in establishing the diagnosis as clinical,
      laboratory, and histological features could mimic other uveitis entities.
      METHODS: Case reports of three patients. RESULTS: The first patient was an
      African male suffering from a chronic bilateral keratoconjunctitivitis that was
      initially misdiagnosed as a chronic allergic conjunctivitis. The second patient
      was an Italian female who presented with bilateral vitritis, whereas the third
      patient was an Italian male suffering from a chronic bilateral panuveitis. The
      diagnosis of ocular Whipple in the first and third case was made by a positive T.
      whipplei PCR from the ocular specimen, and the second patient had detection of T.
      whipplei from extraocular sites. CONCLUSIONS: Whipple disease can have protean
      manifestations in the eye including an isolated ocular surface involvement
      manifested as keratitis.

PMID- 30192689
TI  - Development of Visual Detection of alpha-Thalassemia-1 (the - -SEA Deletion)
      Using pH-Sensitive Loop-Mediated Isothermal Amplification.
AB  - Detection of alpha-thalassemia-1 (alpha-thal-1) carriers provides valuable
      insight for genetic consulting in prevention and control programs for couples who
      are at risk of conceiving a fetus with severe thalassemia, both Hb Bart's hydrops
      fetalis and hemolytic Hb H disease. The traditional method is complicated, time
      consuming and requires high instrument cost and expertise. Loop-mediated
      isothermal amplification (LAMP) based on pH-sensitive dye technology, shows all
      the characteristics required of a real-time analysis with simple operation for
      potential use in the clinical diagnosis of high incidence alpha-thal-1 [Southeast
      Asian (SEA) or - -SEA deletion]. Four primers specific for six distinct regions
      of the alpha-globin gene deletion were designed and analyzed by LAMP using the pH
      indicator dye, phenol red. The amplification of the - -SEA deletion changed the
      color of phenol red from pink to orange. The diagnostic ability of detection of
      the - -SEA deletion by pH-sensitive LAMP was validated using both known and
      unknown blood samples and compared to the conventional polymerase chain reaction
      (PCR) method. Color inspection of pH-sensitive LAMP products could clearly
      identify the - -SEA deletion. There was no cross reaction with a normal alpha
      globin gene, alpha-thal-1 Thai (- -THAI deletion), alpha-thal-2 [-alpha3.7
      (rightward) and -alpha4.2 (leftward) deletion] and beta-thalassemia (beta-thal).
      Detection of the SEA deletion by pH-sensitive LAMP was consistent as compared to
      conventional PCR. The pH-sensitive LAMP method developed for this deletion
      carrier diagnosis has high sensitivity, specificity, simplicity, and requires
      simple instrumentation that makes it applicable for resource-limited laboratories
      in rural areas of developing countries.

PMID- 30192691
TI  - Diffusion tensor imaging based white matter changes and antioxidant enzymes
      status for early identification of mild cognitive impairment.
AB  - Mild cognitive impairment (MCI) is an early stage of dementia. The changes in
      white matter integrity and antioxidant enzymes levels are crucial in onset and
      progression to Alzheimer's disease (AD). To elucidate the changes in cognitive
      performance, white matter integrity, oxidative stress marker, for early detection
      of prodromal state of AD. Fifty cases of MCI and controls (55-75 years) were
      subjected to Mini Mental State Examination (MMSE), diffusion tensor imaging (DTI)
      followed by estimation of superoxide dismutase, glutathione peroxidase and lipid
      peroxidation in serum of MCI and control population. The MMSE scores of MCI
      subjects were (28+/-2 - 22.6+/-1) as compared with controls (28+/-1- 29+/-1). DTI
      metrics fractional anisotropy (FA) values in right and left frontal lobe, fornix,
      corpus callosum, while apparent diffusion coefficient (ADC) values in right
      temporal lobe, hippocampus head, corpus callosum right, and forcep major were
      significantly altered in MCI as compared with controls. Superoxide dismutase,
      glutathione peroxidase level were lower while lipid peroxidation marker
      malondialdehyde (MDA) was increased in patients with MCI as compared with
      controls. The study emphasized that changes in neuro-psychological performance,
      white matter integrity and antioxidant enzymes level provide early signature for
      diagnosis of MCI.

PMID- 30192692
TI  - Continued Challenges to the Adoption and Implementation of Survivorship Care
      Plans.

PMID- 30192693
TI  - Human Papillomavirus Testing in Head and Neck Carcinomas: ASCO Clinical Practice
      Guideline Endorsement Summary of the CAP Guideline.

PMID- 30192694
TI  - Examining factors affecting patients trust in online healthcare services in
      China: The moderating role of the purpose of use.
AB  - With the development of Web 2.0 technologies, an increasing number of websites
      are providing online healthcare services, and they have potential to alleviate
      problems of overloaded medical resources in China. However, some patients are
      reluctant to trust and continue using online healthcare services, partly due to
      the immature development of healthcare websites. Previous research has argued
      that online trust is significantly associated with the risk or benefit perceived
      by users. This study aims to extend prior research and examine how perceptual
      factors influence patients' online trust and intention to continue using online
      healthcare services. We developed a model with the moderating role of purpose of
      use and tested it with data collected from 283 participants. The results support
      the validity of the model and most hypotheses. The moderating role of purpose of
      use between the perceived benefits/risks and patients' online trust is also
      highlighted. Theoretical and practical implications are also discussed.

PMID- 30192695
TI  - Effect of Ubiquinol Intake on Defecation Frequency and Stool Form: A Prospective,
      Double-Blinded, Randomized Control Study.
AB  - Bowel habits affect the quality of life (QOL) of patients with functional
      gastrointestinal disorders. This study evaluated the effects of reduced form
      coenzyme Q 10 (ubiquinol) intake on defecation frequency and stool form in
      patients with daily abdominal symptoms. This was a single-center, prospective,
      double-blind, randomized control study. Forty-one patients who had the daily
      symptom of constipation or diarrhea were randomly assigned at a 1:1 ratio to
      receive either ubiquinol (150 mg/day) or placebo for 12 weeks. Patients completed
      a daily diary to collect information regarding their numbers of defecations and
      stool forms according to the Bristol Stool Form (BSF) Scale for 7 days at
      baseline and 12 weeks. QOL was assessed using the 36-item short-form (SF-36) at
      baseline and 12 weeks. Twenty-one patients were assigned to the ubiquinol group,
      and 20 were assigned to the placebo group. At 12 weeks, the mean defecation
      frequency, compared to baseline, significantly decreased in the ubiquinol group (
      0.1 times/day, P = .034) and increased in the placebo group (+0.3 times/day, P =
      .004). There was no significant change in the 12-week BSF Scale score of the
      ubiquinol group (+0.2, P = .123), whereas that of the placebo group was increased
      (+0.5, P < .001). The 12-week general health perception SF-36 score was
      significantly increased in the ubiquinol group (+3.5, P = .045), whereas there
      was no significant difference in that score in the placebo group (+1.2, P =
      .178). In conclusion, taking ubiquinol for 12 weeks decreased defecation
      frequencies and increased the QOL score, suggesting that ubiquinol may change the
      bowel habits and improve QOL in patients with abdominal distress.

PMID- 30192696
TI  - Embedding persuasive design for self-health management systems in Dutch
      healthcare informatics education: Application of a theory-based method.
AB  - The development of eHealth is dramatically changing the way healthcare is
      provided and organized. eHealth applications are used not only by healthcare
      professionals but also by patients specifically to self-manage their health
      condition. The development of eHealth applications requires a new methodological
      approach, departing from the more conventional methods dedicated to designing
      health information systems. There is a gap between theories to design persuasive
      eHealth applications and practices. In the Netherlands, eHealth innovation
      emerges from three areas. In research, the development of eHealth application
      often remains in a pilot phase. Healthcare organizations are also keen to
      innovate but do not always have the know-how. We further witness technology push
      from business and industry, undermining the co-creation process of the
      innovation. We consequently advocate an integrated, systematic and practical but
      scientifically based methodology to design effective persuasive eHealth
      applications. This approach is being successfully embedded in our educational
      health informatics program.

PMID- 30192697
TI  - The individual and household impacts of cataract surgery on older blind adults in
      ethiopia.
AB  - PURPOSE: To comprehensively measure the impacts of cataract surgery on patients'
      activities and mental and physical health, caregivers' well-being, and household
      incomes in a resource-poor setting Methods: One thousand two hundred thirty-four
      bilaterally blind older adults in Amhara region, Ethiopia, were interviewed at
      baseline and 1030 (83%) re-interviewed at follow-up 1 year later. Six hundred
      ninety three (45%) at baseline were diagnosed with cataracts and offered free
      surgery, of which 484 (73%) were operated. Difference-in-difference was used to
      estimate impacts of surgery, using surgery-ineligible, mostly non-cataract blind
      as controls. RESULTS: For patients, surgery resulted in a 0.31 standard deviation
      increase in an index of social participation (p < 0.001), a 30% proportional
      increase in ability to perform activities of daily living (p < 0.001), and a 17%
      proportional reduction in Center for Epidemiologic Studies Depression Scale (CES
      D) depression score (p < 0.001). A small (6%) increase in work participation
      occurred among men (p = 0.093) in this elderly sample. No change occurred in
      individual or household food insecurity, household consumption, or assets.
      Caregivers' mental health improved slightly (7.3% proportional reduction in CES
      D; p = 0.024). Estimates show no change in caregiver work participation or social
      participation; however, subjective responses regarding changes from surgery
      suggest that reduced caregiving time was an important benefit to households.
      CONCLUSION: Cataract surgery significantly improved the vision as well as mental
      health, social engagement, and physical functioning of older adults. However,
      increases in work participation were very limited, likely reflecting the advanced
      age of the patients (mean = 76 years); in addition, possibly, to cumulative
      impacts of blindness on ability to work or on household assets. Earlier surgery
      may lead to larger economic effects.

PMID- 30192698
TI  - Temporal Trends and Geographic Patterns of Lung Cancer Incidence by Histology in
      Thailand, 1990 to 2014.
AB  - Purpose Lung cancer is one of the most common cancers worldwide and in Thailand.
      We characterize and forecast region-specific patterns of lung cancer incidence by
      histology and sex. Methods We analyzed lung cancer incidence trends in Thailand
      by histology (adenocarcinoma [AdC]; squamous cell carcinoma [SCC]; and large
      cell, small-cell, and other carcinomas) from 1990 to 2014 in four cancer
      registries in three regions (north, Chiang Mai Province and Lampang Province;
      northeast: Khon Kaen Province; south: Songkhla Province). Annual percent change
      (APC) was calculated to quantify the incidence rate trends using joinpoint
      regression. Age-period-cohort models were used to examine the temporal trends of
      AdC and SCC by age, calendar year, and birth cohort. We projected the incidence
      of AdC and SCC up to 2030 using three independent approaches: joinpoint, age
      period-cohort, and Nordpred models. Results AdC incidence significantly increased
      from 1990 to 2012 in Chiang Mai males (APC, 1.3%), Songkhla males from 2004 to
      2014 (APC, 2.5%), Songkhla females from 1990 to 2014 (APC, 5.9%), and Khon Kaen
      females from 2005 to 2014 (APC, 3.1%). Conversely, SCC incidence significantly
      decreased from 1990 to 2012 in Chiang Mai males and females (APC, -1.2% and 
      4.8%, respectively), Lampang males and females from 1993 to 2014 (APC, -5.4% and 
      5.2%, respectively), and Songkhla females from 1990 to 2014 (APC, -2.1%). In
      general, trends of AdC and SCC correlated more with birth cohort than with
      calendar year. Three projection models suggested that incidence rates of AdC in
      Songkhla may continue to increase until 2030. Conclusion Temporal trends of lung
      cancer by histology varied among regions in Thailand. Reduction of lung cancer
      incidence in Thailand likely will require prevention strategies tailored to each
      specific region.

PMID- 30192699
TI  - Improving efficacy of cancer immunotherapy through targeting of macrophages.
AB  - T cell-based immunotherapies have revolutionized the treatment against cancer.
      But complete and long-lasting efficacy is only observed in a fraction of the
      patient population. One of the suspected causes is the inability of cytotoxic T
      cells, endowed with tumor killing ability, to reach their malignant targets.
      Using dynamic fluorescence imaging to study the dynamic of T cells in tumors from
      patients with lung cancer, we have recently demonstrated that macrophages trap
      the T lymphocytes, which are not longer able to contact the tumor cells. In
      murine models of breast cancer, we could show that the depletion of macrophages
      allows T cells to interact with tumor cells, a process which enhances anti-PD-1
      immunotherapy. These findings illustrate the relevance of current clinical trials
      combining a strategy that deplete or modulate macrophages with anti-PD-1
      immunotherapy.

PMID- 30192701
TI  - Corrigendum.

PMID- 30192700
TI  - Mucormycosis Endophthalmitis in a Silicone Oil-Filled Eye of an Immunocompetent
      Patient.
AB  - PURPOSE: Fungal endophthalmitis following pars plana vitrectomy with silicone oil
      tamponade is an infrequent entity. Filamentous fungi like aspergillus are
      generally associated with endophthalmitis. Mucor is a rarely implicated pathogen
      in cases of endophthalmitis with only two reported cases in medical literature.
      Both these cases had uncontrolled diabetes which predisposed them to develop
      mucor endophthalmitis. METHODS: We report a non-diabetic patient who developed
      mucor endophthalmitis after uneventful vitreous surgery for myopia associated
      retinal detachment. RESULTS: Mucor species induced endophthalmitis in a silicone
      oil-filled eye of a non-diabetic patient is reported. The eye went into pthisis
      bulbi. CONCLUSIONS: To the best of our knowledge, this is the first report of
      mucor endophthalmitis in a silicone oil-filled globe of an immunocompetent
      patient.

PMID- 30192702
TI  - Production of recombinant TSA-1 and evaluation of its potential for the immuno
      therapeutic control of Trypanosoma cruzi infection in mice.
AB  - A therapeutic vaccine for human Chagas disease (American trypanosomiasis caused
      by Trypanosoma cruzi) is under development based on the success of vaccinating
      mice with DNA constructs expressing the antigens Tc24 and Tc-TSA-1. However,
      because DNA and nucleic acid vaccines produce less than optimal responses in
      humans, our strategy relies on administering a recombinant protein-based vaccine,
      together with adjuvants that promote Th1-type immunity. Here we describe a
      process for the purification and refolding of recombinant TSA-1 expressed in
      Escherichia coli. The overall yield (20-25%) and endotoxin level of the purified
      recombinant TSA-1 (rTSA-1) is suitable for pilot scale production of the antigen
      for use in phase 1 clinical trials. Mice infected with T. cruzi were treated with
      rTSA-1, either alone or with Toll-like receptor 4 (TLR-4) agonist adjuvants
      including monophosphoryl lipid A (MPLA), glucopyranosyl lipid A (GLA, IDRI), and
      E6020 (EISEI, Inc). TSA-1 with the TLR-4 agonists was effective at reducing
      parasitemia relative to rTSA-1 alone, although it was difficult to discern a
      therapeutic effect compared to treatment with TLR-4 agonists alone. However, rTSA
      1 with a 10 ug dose of MPLA optimized reductions in cardiac tissue inflammation,
      which were significantly reduced compared to MPLA alone. It also elicited the
      lowest parasite burden and the highest levels of TSA-1-specific IFN-gamma levels
      and IFN-gamma/IL-4 ratios. These results warrant the further evaluation of rTSA-1
      in combination with rTc24 in order to maximize the therapeutic effect of vaccine
      linked chemotherapy in both mice and non-human primates before advancing to
      clinical development.

PMID- 30192704
TI  - Using thermochromism to simulate blood oxygenation in extracorporeal membrane
      oxygenation.
AB  - INTRODUCTION: Extracorporeal membrane oxygenation (ECMO) training programs employ
      real ECMO components, causing them to be extremely expensive while offering
      little realism in terms of blood oxygenation and pressure. To overcome those
      limitations, we are developing a standalone modular ECMO simulator that
      reproduces ECMO's visual, audio and haptic cues using affordable mechanisms. We
      present a central component of this simulator, capable of visually reproducing
      blood oxygenation color change using thermochromism. METHODS: Our simulated ECMO
      circuit consists of two physically distant modules, responsible for adding and
      withdrawing heat from a thermochromic fluid. This manipulation of heat creates a
      temperature difference between the fluid in the drainage line and the fluid in
      the return line of the circuit and, hence, a color difference. RESULTS:
      Thermochromic ink mixed with concentrated dyes was used to create a recipe for a
      realistic and affordable blood-colored fluid. The implemented "ECMO circuit"
      reproduced blood's oxygenation and deoxygenation color difference or lack
      thereof. The heat control circuit costs 300 USD to build and the thermochromic
      fluid costs 40 USD/L. During a ten-hour in situ demonstration, nineteen ECMO
      specialists rated the fidelity of the oxygenated and deoxygenated "blood" and the
      color contrast between them as highly realistic. CONCLUSIONS: Using low-cost yet
      high-fidelity simulation mechanisms, we implemented the central subsystem of our
      modular ECMO simulator, which creates the look and feel of an ECMO circuit
      without using an actual one.

PMID- 30192703
TI  - The attitudes, behaviors, and knowledge of healthcare professionals towards the
      diagnosis, treatment, and prevention of bacterial meningitis in Turkey.
AB  - INTRODUCTION: Bacterial meningitis is one of the leading causes of morbidity and
      mortality among children and adults. Better understanding of the seroepidemiology
      of meningitis is critical for both the selection and implementation of an
      effective meningitis vaccine for the national immunization program. Because
      physicians play a crucial role in the implementation of this vaccine, the aim of
      this study was to evaluate the attitudes, behaviors, and knowledge of healthcare
      professionals in Turkey regarding the diagnosis, treatment and prevention of
      bacterial meningitis, especially pneumococcal and meningococcal meningitis.
      METHODS: This study used a cross-sectional electronic survey with a national
      convenience sample of 339 physicians (171 pediatric age specialists [PAS] and 168
      adult patient specialists [APS]) in Turkey. A web-based questionnaire which
      consisted 28 questions about the definition, diagnosis, and treatment of
      bacterial as well as knowledge and/or attitudes about meningococcal vaccines, was
      designed. RESULTS: Approximately 72.9% (n = 247) of the respondents followed a
      patient with meningitis in the last year. A 49.5% of participants preferred to
      perform computerized cranial tomography (CCT) for suspected meningitis cases
      before lumbar puncture (LP) at 75-100% frequency (27.5% PAS; 72% APS, p < .01).
      In addition 27.1% of the respondents reported using a routine steroid as an
      adjunctive treatment (19% PAS; 35% APS, p < .01). For meningococcal meningitis,
      72.5% of the participants preferred to use third-generation cephalosporins (63.1%
      PAS; 82.1% APS, p < .05). For pneumococcal meningitis, approximately 50% of the
      participants preferred to use a third-generation cephalosporin plus glycopeptide
      (41.5% PAS; 58.9% APS, p < .05). While 32.7% of the sample preferred to
      administer a 7-day course of antibiotics for meningococcal meningitis, 40.9%
      preferred a course of 14 days or more. For pneumococcal meningitis, 88.4% of the
      sample preferred a 10-14 day course of antibiotics. In addition, 67% of the PAS
      group and 50% (p < .001) of the APS group thought that a conjugated meningococcal
      vaccine should be a part of the National Immunization Program. The top five
      groups recommended for routine immunization included all children,
      asplenia/splenectomy patients, immunodeficient patients, those who planned to
      travel to endemic areas, including Hajj, and military personnel. CONCLUSION: In
      this large convenient sample of physicians in Turkey, we showed that there are
      heterogenous approaches to the diagnosis and treatment of bacterial meningitis,
      also differences between pediatricians and non-pediatricians regarding their
      beliefs and attitudes, which may be due to differences in the epidemiology and
      clinical presentation between children and adults. We observed appropriate but
      unnecessary extended courses of antibiotics for meningitis. Most of the
      participants thought that children are a vulnerable risk group that should
      potentially be immunized and that meningococcal vaccines should be included in
      the National Immunization Program. Our results imply that more awareness is
      needed regarding diagnosis, treatment, and further recommendations for meningitis
      at the country level in Turkey.

PMID- 30192705
TI  - Exposure-based cognitive behavior therapy for atopic dermatitis: an open trial.
AB  - Atopic dermatitis (AD) is a common and debilitating inflammatory dermatological
      disorder and is marked by itch and inflamed skin. Scratching, sleep loss, and
      avoidance of situations associated with more AD symptoms are central hypothesized
      mechanisms that perpetuate the disorder and cause reduced quality of life. We
      developed an exposure-based cognitive behavioral treatment (CBT) that entailed
      mindfulness practice as a means to increase tolerance for aversive experiences
      during exposure. The aim of the present study was to test the treatment's
      acceptability and preliminary efficacy in adults with AD. We used an uncontrolled
      pretest-posttest design and recruited participants (N = 9) from a university
      hospital dermatological clinic. The treatment comprised 10 weekly sessions over
      10 weeks and assessments of AD symptoms as well as psychiatric symptoms and
      quality of life were conducted at baseline, posttreatment and 6-month follow-up.
      The results showed significant and large baseline to posttreatment improvements
      on self-reported measures of AD symptoms (p = .020) and general anxiety (p =
      .005), but there was no significant improvement in depression or quality of life.
      Treatment satisfaction was high and a majority of participants (67%) completed
      the treatment. We conclude that exposure-based CBT for adult AD can be feasible,
      acceptable, and potentially efficacious.

PMID- 30192706
TI  - Combined effects of knee brace, laterally wedged insoles, and toe-out gait on
      knee adduction moment and fall risk in moderate medial knee osteoarthritis
      patients.
AB  - BACKGROUND: Knee osteoarthritis is a major contributor to the global burden of
      disease. There is a need of reducing knee joint load and to improve balance and
      physical function among knee osteoarthritis patients. OBJECTIVES: To test the
      hypothesis that toe-out gait will reduce second peak knee adduction moment
      further and increase fall risk when combined with knee brace and laterally wedged
      insole in knee osteoarthritis patients. STUDY DESIGN: Single visit study with
      repeated measures. METHODS: First and second peak knee adduction moments, fall
      risk and comfort level. First and second peak knee adduction moments were
      determined from three-dimensional gait analysis, completed under six randomized
      conditions: (1) natural, (2) knee brace, (3) knee brace + toe-out gait, (4)
      laterally wedged insole, (5) laterally wedged insole + toe-out gait, and (6) knee
      brace + laterally wedged insole + toe-out gait. Fall risk was assessed by Biodex
      Balance System using three randomized stability settings: (1) static, (2)
      moderate dynamic setting (FR12), and (3) high dynamic setting (FR8). RESULTS: The
      reduction in first peak knee adduction moment and second peak knee adduction
      moment was greatest (7.16% and 25.55%, respectively) when toe-out gait combine
      with knee brace and laterally wedged insole. Significant increase in fall risk
      was observed with knee brace + laterally wedged insole + toe-out gait (42.85%) at
      FR12. Similar significant balance reductions were found at FR8 condition for knee
      brace + toe-out gait (35.71%), laterally wedged insole + toe-out gait (28.57%),
      and knee brace + laterally wedged insole + toe-out gait (50%) as compared to
      natural. However, knee brace decreased fall risk at FR12 by 28.57%. CONCLUSION:
      There is a synergistic effect of toe-out when combined with knee brace and
      laterally wedged insole concurrently in second peak knee adduction moment
      reduction but with a greater degree of fall risk. Simultaneous use of
      conservative treatments also decreases comfort level. Clinical relevance Patients
      with mild and moderate knee osteoarthritis are usually prescribed conservative
      treatment techniques. This study will provide an insight whether or not a
      combination of these techniques have a synergistic effect in reducing knee joint
      load.

PMID- 30192707
TI  - Time to tackle rheumatic heart disease: Data needed to drive global policy
      dialogues.
AB  - Rheumatic heart disease (RHD) is an avoidable disease of poverty that persists
      predominantly in low resource settings and among Indigenous and other high-risk
      populations in some high-income nations. Following a period of relative global
      policy inertia on RHD, recent years have seen a resurgence of research, policy
      and civil society activity to tackle RHD; this has culminated in growing momentum
      at the highest levels of global health diplomacy to definitively address this
      disease of disadvantage. RHD is inextricably entangled with the global
      development agenda, and effective RHD action requires concerted efforts both
      within and beyond the health policy sphere. This report provides an update on the
      contemporary global and regional policy landscapes relevant to RHD, and
      highlights the fundamental importance of good data to inform these policy
      dialogues, monitor systems responses and ensure that no one is left behind.

PMID- 30192708
TI  - Phylogenetic Assignment of Ralstonia pseudosolanacearum (Ralstonia solanacearum
      Phylotype I) Isolated from Rosa spp.
AB  - During the last two years, greenhouse cultivation of rose (Rosa spp.) in the
      Netherlands has been challenged by an uncommon bacterial disease. Affected plants
      suffered from chlorosis, stunting, wilting, and necrosis. The bacterial isolates
      obtained from the different Rosa spp. cultivars were all identified as phylotype
      I, sequevar 33 from the 'Ralstonia solanacearum species complex' (RSSC), actually
      reclassified as Ralstonia pseudosolanacearum. The work in this paper considers
      the genetic diversity and the phylogenetic position of 129 R. pseudosolanacearum
      isolates from the outbreak. This was assessed by AFLP based on four different
      primer combinations and MLP using partial sequences of the egl, mutS, and fliC
      genes. The AFLP revealed identical profiles for all the isolates, irrespective of
      their association with Rosa sp. propagating material, Rosa spp. plants for cut
      flowers, or water used in the different greenhouse cultivations. These AFLP
      profiles were unique and diverged from profiles of all other reference isolates
      in the RSSC included. Furthermore, MLP on egl, fliC, and mutS gene sequences
      clearly demonstrated that all R. pseudosolanacearum isolates clustered in
      phylotype I, as a distinct monophyletic group. Interestingly, this monophyletic
      group also included phylotype I strain Rs-09-161 from eggplant (Solanum
      melongena), isolated in 2009 in India. AFLP and MLP were both efficient in
      revealing the genetic divergence from the RSSC isolates included. The
      phylogenetic tree constructed from the AFLP profiles was, in general, in
      agreement with the one obtained from MLP. Both phylogenetic trees displayed a
      similar clustering, supported by high posterior probabilities. Both methodologies
      clearly demonstrated that the R. pseudosolanacearum isolates from Rosa spp.
      grouped in a monophyletic group inside phylotype I, with a particular
      correspondence to a strain present in India, as revealed in MLP.

PMID- 30192710
TI  - Significance of recumbent curvature in prediction of in-orthosis correction for
      adolescent idiopathic scoliosis.
AB  - BACKGROUND: Prediction of in-orthosis curvature at pre-orthosis stage is valuable
      for the treatment planning for adolescent idiopathic scoliosis, while the
      position of spinal curvature assessment that is effective for this prediction is
      still unknown. OBJECTIVES: To compare the spinal curvatures in different body
      positions for predicting the spinal curvature rendered by orthosis. STUDY DESIGN:
      A prospective cohort study. METHODS: Twenty-two patients with adolescent
      idiopathic scoliosis (mean Cobb angle: 28.1 degrees +/- 7.3 degrees ) underwent
      ultrasound assessment of spinal curvature in five positions (standing, supine,
      prone, sitting bending, prone bending positions) and that within orthosis.
      Differences and correlations were analyzed between the spinal curvatures in the
      five positions and that within orthosis. RESULTS: The mean in-orthosis curvature
      was 11.2 degrees  while the mean curvatures in five studied positions were 18.7
      degrees  (standing), 10.7 degrees  (supine), 10.7 degrees  (prone), -3.5 degrees 
      (prone bending), and -6.5 degrees  (sitting bending). The correlation
      coefficients of the in-orthosis curvature and that in five studied positions were
      r = 0.65 (standing), r = 0.76 (supine), r = 0.87 (prone), r = 0.41 (prone
      bending), and r = 0.36 (sitting bending). CONCLUSION: The curvature in recumbent
      positions (supine and prone) is highly correlated to the initial in-orthosis
      curvature without significant difference. Thus, the initial effect of spinal
      orthosis could be predicted by the curvature in the recumbent positions
      (especially prone position) at the pre-orthosis stage. Clinical relevance
      Prediction of in-orthosis correction at pre-orthosis stage is valuable for spinal
      orthosis design. This study suggests assessing the spinal curvature in recumbent
      position (especially prone position) to predict the initial in-orthosis
      correction for optimizing the orthosis design.

PMID- 30192709
TI  - The Spectrum of Hazing and Peer Sexual Abuse in Sports: A Current Perspective.
AB  - CONTEXT:: Hazing and peer sexual abuse in sport are a critical issue, brought
      into public scrutiny with increasing frequency due to various forms of media,
      resulting in major causes of numerous avoidable mental health issues, and in some
      cases, even death. While the exact incidence of these activities is extremely
      difficult to quantify, trends indicate that the problem is very likely
      underreported. EVIDENCE ACQUISITION:: PubMed, Google, various legal
      journals/statutes, books on hazing and peer abuse in sport, and newspaper
      periodicals/editorials were all searched. Sources range in date from 1968 through
      2018. STUDY DESIGN:: Clinical review. LEVEL OF EVIDENCE:: Level 5. RESULTS::
      Hazing and peer sexual abuse are complex issues that have the potential to lead
      to physical, emotional, and mental harm. The underlying causes of hazing are
      complex but rooted in maintaining a hierarchical structure within the team unit.
      By implementing various changes and strategies, coaches and team administration
      can mitigate the risks of these behaviors. CONCLUSION:: Hazing and peer sexual
      abuse in sport are avoidable and must be eliminated to maximize the numerous
      physical and psychosocial benefits attainable by participating in team athletics.

PMID- 30192711
TI  - Coverage and predictors of influenza vaccination in patients with cystic fibrosis
      in a campaign with a mobile phone text messaging intervention.
AB  - Annual influenza vaccination is considered the best protection against influenza
      infection. We analyzed the influenza vaccine coverage (IVC) in cystic fibrosis
      (CF) patients and evaluated the factors associated with the IVC, including the
      effect of text-message/SMS reminders. We performed a cross-sectional study in the
      Community of Madrid (Spain) in 2015. The target population was people with CF
      older than 6 months of age at the beginning of the flu vaccination campaign. The
      IVC was calculated according to the study variables. A total of 445 CF patients
      were analyzed. In 2015, IVC reached 67.9% and was higher in children and women.
      The main factor associated with flu vaccination was having been vaccinated in the
      previous campaign (aOR 14.36; IC95%: 8.48-24.32). The probability of being
      vaccinated after receiving the SMS was more than twice than for those who did not
      receive it, although no statistical significance was reached. In conclusion the
      IVC of patients with CF is high, but it still has room for improvement. SMS
      reminders sent to CF patients might improve influenza vaccine uptake.

PMID- 30192712
TI  - Fetal growth restriction shortens cardiac telomere length but this is attenuated
      by exercise in early life.
AB  - BACKGROUND AND AIMS: Fetal and postnatal growth restriction predispose to
      cardiovascular disease (CVD) in adulthood. Telomeres are repetitive DNA-protein
      structures that protect chromosome ends, and the loss of these repeats (a
      reduction in telomere length) is associated with CVD. As exercise preserves
      telomere length and cardiovascular health, the aim of this study was to determine
      the effects of growth restriction and exercise training on cardiac telomere
      length and telomeric genes. METHODS AND RESULTS: Pregnant Wistar Kyoto rats
      underwent bilateral uterine vessel ligation to induce uteroplacental
      insufficiency and fetal growth restriction ('Restricted'). Sham operated rats had
      either intact litters ('Control') or their litters reduced to five pups with
      slowed postnatal growth ('Reduced'). Control, Restricted, and Reduced male rats
      were assigned to Sedentary, Early exercise (5-9 weeks of age) or Late exercise
      (20-24 weeks of age) groups. Hearts were excised at 24 weeks of age for telomere
      length and gene expression measurements by qPCR. Growth restriction shortened
      cardiac telomere length (P<0.001) but this was rescued by early exercise
      (P<0.001). Early and Late exercise increased cardiac weight index (P<0.001) but
      neither this nor telomere length was associated with expression of the telomeric
      genes Tert, Terc, Trf2, Pnuts, or Sirt1. DISCUSSION AND CONCLUSIONS: Growth
      restriction shortens cardiac telomere length, reflecting the cardiac pathologies
      associated with low birth weight. Exercise in early life may offer long-term
      protective effects on cardiac telomere length which could help prevent CVD in
      later life.

PMID- 30192713
TI  - Dysbiosis signatures of gut microbiota in coronary artery disease.
AB  - Gut microbiota dysbiosis has been considered to be an important risk factor that
      contributes to coronary artery disease (CAD), but limited evidence exists about
      the involvement of gut microbiota in the disease. Our study aimed to characterize
      the dysbiosis signatures of gut microbiota in coronary artery disease. The gut
      microbiota represented in stool samples were collected from 70 patients with
      coronary artery disease and 98 healthy controls. 16S rRNA sequencing was applied,
      and bioinformatics methods were used to decipher taxon signatures and function
      alteration, as well as the microbial network and diagnostic model of gut
      microbiota in coronary artery disease. Gut microbiota showed decreased diversity
      and richness in patients with coronary artery disease. The composition of the
      microbial community changed; Escherichia-Shigella [false discovery rate (FDR =
      7.5*10-5] and Enterococcus (FDR = 2.08*10-7) were significant enriched, while
      Faecalibacterium (FDR = 6.19*10-10), Subdoligranulum (FDR = 1.63*10-6), Roseburia
      (FDR = 1.95*10-9), and Eubacterium rectale (FDR = 2.35*10-4) were significant
      depleted in the CAD group. Consistent with the taxon changes, functions such as
      amino acid metabolism, phosphotransferase system, propanoate metabolism,
      lipopolysaccharide biosynthesis, and protein and tryptophan metabolism were found
      to be enhanced in CAD patients. The microbial network revealed that
      Faecalibacterium and Escherichia-Shigella were the microbiotas that dominated in
      the healthy control and CAD groups, respectively. The microbial diagnostic model
      based on random forest also showed probability in identifying those who suffered
      from CAD. Our study successfully identifies the dysbiosis signature,
      dysfunctions, and comprehensive networks of gut microbiota in CAD patients. Thus,
      modulation targeting the gut microbiota may be a novel strategy for CAD
      treatment.

PMID- 30192714
TI  - Implicit Bias Predicts Liking of Ingroup Members Who Are Comfortable With
      Intergroup Interaction.
AB  - We test a novel framework for how ingroup members are perceived during intergroup
      interaction. Across three experiments, we found that, above and beyond
      egalitarian attitudes and motivations, White observers' automatic responses to
      Blacks (i.e., their implicit anti-Black bias) shaped their affiliation toward
      ingroup targets who appeared comfortable engaging in interracial versus same-race
      interaction. White observers' implicit anti-Black bias negatively correlated with
      liking of White targets who were comfortable with Blacks (Experiments 1-3). The
      relationship between implicit bias and liking varied as a function of targets'
      nonverbal comfort in interracial interactions (Experiment 1). Specifically,
      implicit bias negatively correlated with liking of targets when targets'
      nonverbal behaviors revealed observers felt comfortable with interracial contact,
      irrespective of the nature of those behaviors (Experiment 2). Finally, the
      relationship between implicit bias and target liking was mediated by perceived
      similarity (Experiment 3). Theoretical implications for stigma-by-association,
      social network homogeneity, and extended contact are discussed.

PMID- 30192716
TI  - Distributed cognition in aviation operations: a gate-to-gate study with
      implications for distributed crewing.
AB  - The network analysis method, Event Analysis of Systemic Teamwork (EAST), was used
      to examine routine aviation operations from multiple perspectives from six key
      areas (i.e. Dispatch, ATC, ATM, Maintenance, Loading, and the Cockpit). Data was
      collected over a five-day observational field trial at an international air cargo
      operator. Researchers recorded the activities of agents operating within the six
      key areas over three outbound and two inbound flights. Three networks (i.e.
      social, information and task) were created for four key phases of flight: (i) pre
      flight checks and engines start (ii) taxi, take-off and assent, (iii) descent,
      landing and taxi, and (iv) park and shut down. The networks represent a 'work
      audit' of short-haul cargo operations, which enabled a detailed understanding of
      the interactions and connections within the current system. Implications for the
      future of distributed crewing concepts are discussed. Practitioner Summary: An
      analysis of the aviation system was undertaken using the amalgamated data from
      three outbound and two inbound flights. These analyses show the social,
      information and task interactions for cargo operations. This has been used to
      specify requirements for future distributed crewing options.

PMID- 30192718
TI  - JIM Reading List.

PMID- 30192717
TI  - Movement perceived as chores or a source of joy: a phenomenological-hermeneutic
      study of physical activity and health.
AB  - Physical activity has become the most documented and acknowledged health advice
      in relation to both staying healthy and regaining health both physically and
      mentally. Thus, physical activity in relation to spinal cord injury, low back
      pain and heart disease is respectively means to regain bodily function, avoid or
      reduce pain and early death. A second analysis of three studies with a
      phenomenological-hermeneutic approach building on Ricoeur's philosophy on how
      people understand themselves and their world through narrative configurations
      revealed that physical activity had different meanings to people. This revealed
      that the meanings of physical activity could range from movements being
      unpleasant, maybe even painful to movements being a source of joy. This caused
      participants (1) to engage in movement as a source of joy, (2) to overcome the
      bodily struggle to do their chores, and maybe feel better as a result or (3) to
      minimize bodily functions equivalent to a functional daily life. Illustrated by
      10 different approaches this provides knowledge about driving forces for health
      professional support. As joy and passion are the strongest driving forces to
      physical activity, this highlights the importance of supporting people to find a
      kind of physical activity that they like.

PMID- 30192715
TI  - Extraction of premolars for orthodontic reasons on the decline? A cross-sectional
      survey of BOS members.
AB  - OBJECTIVE: To obtain the opinion of British Orthodontic Society (BOS) members in
      relation to possible patterns of prescription of orthodontic extractions over the
      past 5-10 years and to relate any changes identified to treatment objectives,
      facial and smile aesthetics, and treatment strategies and adjuncts. DESIGN: Cross
      sectional questionnaire. SETTING: On-line survey of BOS members. METHODS: A 14
      item on-line questionnaire was sent to orthodontic practitioners for completion.
      The questionnaire covered demographics, possible changes in frequency of
      prescribed extractions with specific information concerning the effect of patient
      age, and the influence of other factors including alternative approaches to space
      creation, evolving treatment mechanics, smile and facial aesthetics, and
      retention protocols. RESULTS: Two hundred and eight responses were obtained with
      95.6% (n = 199) reporting reduced extraction prescription over the last 5-10
      years. Overall, 29.9% and 35.5% felt that their threshold for extractions had
      increased by more than 2 mm in adolescents and adults, respectively. Facial (n =
      145; 69.7%) and smile (n = 127; 61.1%) aesthetics, and increased use of inter
      proximal reduction (n =  102; 49%) were the factors most frequently reported as
      having either a moderate or major influence on this trend. Based on ordinal
      logistical regression analyses, no significant relationship was found between
      threshold for extractions and work setting (P =  0.675; O.R. 0.51; 95% CI: 0.39,
      1.85) or level of orthodontic experience (P =  0.15; O.R. 1.02; 95% CI: 0.15,
      1.05), although a higher threshold for extractions was more likely among users of
      conventional than self-ligating brackets (P =  0.001; O.R. 4.74; 95% CI: 1.95,
      11.5). CONCLUSIONS: A reduced tendency to prescribe orthodontic extractions over
      the past 5-10 years among British Orthodontic Society members was identified.
      Comparative clinical research exploring the relative merits of extraction and non
      extraction approaches could be timely.

PMID- 30192719
TI  - An Irregular Rhythm with Missing P Waves.
AB  - An electrocardiogram on a life insurance applicant with a history of surgically
      repaired congenital heart disease displays an irregular rhythm with occasional
      missing P waves.

PMID- 30192721
TI  - Neck Mass in a Five-year-old Afghan Child.

PMID- 30192720
TI  - All-Cause Mortality for Life Insurance Applicants with a Family History of
      Coronary Artery Disease Before 60.
AB  - OBJECTIVE: -To determine the all-cause mortality of life insurance applicants
      having a family history of coronary artery disease (CAD) before age 60.
      BACKGROUND: -Epidemiological studies have shown that a family history of
      premature CAD is an independent risk factor for CAD events. The strength of the
      association between family history and CAD is greatest with earlier age of
      presentation of CAD in the family member and when multiple family members are
      affected. Despite earlier insurance studies on this relationship, there is sparse
      current data on the association between family history of CAD and all-cause
      mortality in life insurance applicants. METHODOLOGY: -Life insurance applicants
      with reported family history of Coronary Artery Disease (CAD) were extracted from
      data covering United States residents between October 2009 and October 2016.
      Information about these applicants was matched to the Social Security Death
      Master (SSDMF) file for deaths occurring from 2009 to 2012 and to another
      commercially available death source file (Other Death Source, ODS) for deaths
      occurring from 2009 to 2016 to determine vital status. Actual to Expected (A/E)
      mortality ratios were calculated using the Society of Actuaries 2015 Valuation
      Basic Table (2015VBT), select and ultimate table (age last birthday). All
      expected bases were not smoker distinct. Confidence bands around these mortality
      ratios were calculated. The variables of interest were applicant age, gender,
      number of family members with CAD before age 60, and the presence of cardiac or
      cardiovascular conditions. RESULTS: -Overall, the mortality of applicants with
      family members with a history of CAD before age 60 was slightly lower than
      expected mortality based on the 2015 VBT. Applicants with a cardiac or
      cardiovascular comorbid condition had a significantly higher mortality ratio. For
      applicants aged 25-54 and 65-75 with cardiac comorbid conditions, the mortality
      ratio was 2 times that of those without a cardiac comorbid condition. For those
      aged 55-64 with cardiovascular comorbid conditions, the mortality ratio was 2.9
      times that of those without a cardiovascular comorbid condition. Females had a
      slightly higher mortality ratio for all age groups, number of family members with
      CAD before age 60, and cardiovascular conditions. CONCLUSION: -A family history
      of CAD before the age of 60 in an insurance applicant may be associated with
      increased all-cause mortality. Overall in this study, life insurance applicants
      had a mortality slightly lower than the expected mortality based on the 2015 VBT.
      However, applicants with a positive family history and a cardiac or
      cardiovascular comorbid condition had a significantly higher mortality ratio.

PMID- 30192722
TI  - Takotsubo Syndrome - Case Review.

PMID- 30192724
TI  - The Vanishing Art of Medical Underwriting.

PMID- 30192723
TI  - Thyroid Cancer: 20-Year Comparative Mortality and Survival Analysis of Six
      Thyroid Cancer Histologic Subtypes by Age, Sex, Race, Stage, Cohort Entry Time
      Period and Disease Duration (SEER*Stat 8.3.2) A Systematic Review of 145,457
      Cases for Diagnosis Years 1993-2013.
AB  - BACKGROUND: -Incidence and prognosis of cancers of the endocrine glands vary
      greatly by stage and histologic type, and, thyroid cancer accounts for most (92%)
      of the cancers of the endocrine glands. It is the 8th most common of cancers and
      has been rising in incidence since 1975. It remains a formidable health threat in
      the United States in 2016 with estimated cases of 64,300 and 1980 deaths.
      OBJECTIVE: -Provide 20-year comparative mortality analysis of thyroid cancer in a
      recent group of 145,457 staged cases (97.5%) of a total of 149,202 patients
      during the 1993-2013 entry time-period in six histologic subtypes by age, sex,
      race, stage and disease duration. METHODS: -Population-based data from SEER
      registries, 1 1973-2013, (SEER*Stat 8.3.2.) were analyzed. RESULTS: - Tables 1 -
      8 provide basic SEER epidemiologic, demographic, case-statistics, and comparative
      mortality follow-up data of 4 principal and 2 supplementary thyroid cancer
      oncotypes by age, sex, race, stage and disease duration of patients in the 1993
      2013 time-period. [Table: see text] [Table: see text] [Table: see text] [Table:
      see text] [Table: see text] [Table: see text] [Table: see text] [Table: see text]
      Conclusions.-Thyroid cancer when localized has a very good prognosis, with no
      significant excess mortality after diagnosis in papillary and papillary
      follicular variant cancers (PFV). Because nearly two thirds of thyroid cancers
      are localized, and excess death rate (EDR) is small in patients with regional
      cancer under age 50, overall excess mortality for all ages also virtually
      disappeared after 10 years in papillary and follicular cancer. Overall, the 5
      year survival rate is greater than 90% for papillary and follicular carcinomas.
      Nevertheless, because of the marked predominance of papillary carcinoma, the
      continued increase in its relative frequency and annual projected deaths, thyroid
      carcinoma remains a significant health concern in the current era.

PMID- 30192726
TI  - A Man (or a Woman) is Known by the Company He/She Keeps.

PMID- 30192725
TI  - Does an Absent Left Main Lead to a Main Event?
AB  - This is a case report of a 29-year-old, male applicant for life insurance who was
      discovered to have an absence of the left main coronary artery (LMCA), with the
      left anterior descending coronary artery (LAD) and left circumflex coronary
      artery (LCX) each arising directly from the left sinus of Valsalva. A brief
      review of several types of coronary artery anatomic variants will be presented.

PMID- 30192727
TI  - Recovery of zinc and copper from copper smelter flue dust. Optimisation of
      sulphuric acid leaching.
AB  - Copper smelter flue dust is a residue, rich in zinc, originating from the
      pyrometallurgical process of copper, and constitutes a potential raw material for
      zinc production. In order to valorise this waste by hydrometallurgical processes,
      its leaching with sulphuric acid at constant pH is studied. Experimental
      conditions (temperature, pH, and pulp density) are optimised by design of
      experiments in order to maximise Zn and Cu extractions while minimising the
      leaching of Fe. The experimental results are fitted to a full-quadratic second
      order equation model by applying multiple regression analysis for extractions of
      Zn, Cu, and Fe. In order to determine the optimum conditions, the response
      surfaces are overlaid and the intersection of the plot of the three responses
      identifies conditions of pH and pulp density that satisfy recoveries of Zn higher
      than 95%, recoveries of Cu around 70%, and Fe extractions lower than 35%. Under
      the best conditions, that is, pH = 2, 10% of pulp density, and at 25 degrees C, a
      liquor rich in zinc and copper, and a lead concentrate are obtained.

PMID- 30192728
TI  - We can learn a lot from drug adverse effects.

PMID- 30192729
TI  - Calcium and vitamin D: To supplement or not?

PMID- 30192730
TI  - Coronary artery calcium scoring: A valuable tool in primary care.

PMID- 30192731
TI  - What can we do about musculoskeletal pain from bisphosphonates?

PMID- 30192732
TI  - How should we diagnose and manage checkpoint inhibitor-associated colitis?

PMID- 30192733
TI  - Obesity: Are shared medical appointments part of the answer?
AB  - Shared medical appointments, in which a multidisciplinary team of healthcare
      providers meets with multiple patients in a group setting, may be an option for
      treating patients with obesity. To be effective, shared medical appointments need
      to address patients' nutrition, physical activity, appetite suppression, stress
      management, and sleep.

PMID- 30192734
TI  - Coronary artery calcium scoring: Its practicality and clinical utility in primary
      care.
AB  - Coronary artery calcium scoring is useful as a risk-stratification tool in
      coronary artery disease, and it outperforms other risk-assessment methods.
      American College of Cardiology/American Heart Association guidelines give the
      test a IIB recommendation in clinical scenarios in which risk stratification is
      uncertain. However, if the test is not used in the appropriate clinical setting,
      misinterpretation of the results can lead to unnecessary cardiac testing. This
      review provides the primary care provider with basic knowledge about the test's
      clinical utility, interpretation, risks, and limitations.

PMID- 30192735
TI  - Shortness of breath, fever, cough, and more in an elderly woman.

PMID- 30192736
TI  - Fournier gangrene.

PMID- 30192737
TI  - Brain abscesses in a 60-year-old man.

PMID- 30192738
TI  - To the Editor: Aortic aneurysm: Fluoroquinolones, genetic counseling.

PMID- 30192739
TI  - To the Editor: Aortic aneurysm: Fluoroquinolones, genetic counseling.

PMID- 30192740
TI  - In reply: Aortic aneurysm: Fluoroquinolones, genetic counseling.

PMID- 30192742
TI  - Growth and electronic structure of 2D hexagonal nanosheets on a corrugated
      rectangular substrate.
AB  - Graphene and h-BN are grown by chemical vapor deposition in ultra high vacuum
      conditions on the Pt(110) surface. Scanning tunneling microscopy measurements and
      low-energy electron diffraction data indicate that graphene forms a variety of
      differently oriented incommensurate domains although with a strong preference to
      align its [Formula: see text] direction with the [Formula: see text] direction of
      Pt. Meanwhile, h-BN exhibits a c(8 * 10) commensurate superstructure, which
      presents a high level of defectivity that implies local variation of the
      periodicity (i.e. mixed c(8 * 10) and c(8 * 12) patches) and the introduction of
      local defects. The combination of advanced photoemission spectroscopy data (angle
      resolved photoemission spectroscopy from the valence band) and ab initio
      calculations indicates that both 2D materials interact weakly with the substrate:
      graphene exhibits neutral doping and is morphologically flat, even if it
      nucleates on the relatively highly corrugated rectangular (110) surface. In the
      case of h-BN, the interaction is slightly stronger and is characterized by a
      small electron transfer from surface Pt atoms to nitrogen atoms. The (110)
      termination of Pt is therefore a quite interesting surface for the growth of 2D
      materials because given its low symmetry, it may favor the growth of selectively
      oriented domains but does not affect their pristine electronic properties.

PMID- 30192743
TI  - MicroRNA 199a Is Downregulated in Patients After Coronary Artery Bypass Graft
      Surgery and Is Associated with Increased Levels of Sirtuin 1 (SIRT 1) Protein and
      Major Adverse Cardiovascular Events at 3-Year Follow-Up.
AB  - BACKGROUND The cardioprotective protein SIRT1 is elevated in patients with
      coronary artery disease (CAD) to compensate for the disease-related adverse
      effects, but less is known about the prognostic role of SIRT 1 regulating
      microRNAs in patients after coronary artery bypass graft (CABG) surgery. MATERIAL
      AND METHODS The expression of the SIRT 1-specific microRNAs miR-199a and miR-195
      was analyzed using real-time PCR in 68 patients referred for CABG surgery and 34
      control patients undergoing heart valve surgery. In CABG patients, major adverse
      cardiac and cerebrovascular events (MACCEs), including all-cause death,
      myocardial infarction (MI), re-vascularization, heart failure symptoms >=NYHA II,
      re-hospitalization for any cardiovascular reason, and stroke, were analyzed at a
      median follow-up (FU) of 3.2 years (range: 3.0-3.6). RESULTS The level of miR
      199a in patients with CAD was significantly reduced compared to the control group
      (relative expression: 0.89+/-0.49 vs. 1.90+/-0.90, p=0.001), while SIRT 1 protein
      was markedly enhanced (p<0.001). In patients undergoing CABG who had MACCEs, miR
      199a was significantly lower compared to patients with an uneventful FU (0.71+/
      0.25 vs. 0.98+/-0.53, p=0.007). Heart failure status, death, and total MACCEs
      rate were inversely correlated with the amount of miR-199a (p=0.039) at 3-year
      FU. CONCLUSIONS Altered expression of miR-199a in myocardial tissue was found to
      be associated with SIRT 1 upregulation in patients with CAD undergoing CABG and
      was associated with an increased MACCEs rate at mid-term follow-up.

PMID- 30192741
TI  - DET1-mediated degradation of a SAGA-like deubiquitination module controls H2Bub
      homeostasis.
AB  - DE-ETIOLATED 1 (DET1) is an evolutionarily conserved component of the
      ubiquitination machinery that mediates the destabilization of key regulators of
      cell differentiation and proliferation in multicellular organisms. In this study,
      we provide evidence from Arabidopsis that DET1 is essential for the regulation of
      histone H2B monoubiquitination (H2Bub) over most genes by controlling the
      stability of a deubiquitination module (DUBm). In contrast with yeast and
      metazoan DUB modules that are associated with the large SAGA complex, the
      Arabidopsis DUBm only comprises three proteins (hereafter named SGF11, ENY2 and
      UBP22) and appears to act independently as a major H2Bub deubiquitinase activity.
      Our study further unveils that DET1-DDB1-Associated-1 (DDA1) protein interacts
      with SGF11 in vivo, linking the DET1 complex to light-dependent ubiquitin
      mediated proteolytic degradation of the DUBm. Collectively, these findings
      uncover a signaling path controlling DUBm availability, potentially adjusting
      H2Bub turnover capacity to the cell transcriptional status.

PMID- 30192744
TI  - Co-evolution networks of HIV/HCV are modular with direct association to structure
      and function.
AB  - Mutational correlation patterns found in population-level sequence data for the
      Human Immunodeficiency Virus (HIV) and the Hepatitis C Virus (HCV) have been
      demonstrated to be informative of viral fitness. Such patterns can be seen as
      footprints of the intrinsic functional constraints placed on viral evolution
      under diverse selective pressures. Here, considering multiple HIV and HCV
      proteins, we demonstrate that these mutational correlations encode a modular co
      evolutionary structure that is tightly linked to the structural and functional
      properties of the respective proteins. Specifically, by introducing a robust
      statistical method based on sparse principal component analysis, we identify near
      disjoint sets of collectively-correlated residues (sectors) having mostly a one
      to-one association to largely distinct structural or functional domains. This
      suggests that the distinct phenotypic properties of HIV/HCV proteins often give
      rise to quasi-independent modes of evolution, with each mode involving a sparse
      and localized network of mutational interactions. Moreover, individual inferred
      sectors of HIV are shown to carry immunological significance, providing insight
      for guiding targeted vaccine strategies.

PMID- 30192746
TI  - Demography and the dual epidemics of tuberculosis and HIV: Analysis of cross
      sectional data from Sub-Saharan Africa.
AB  - BACKGROUND: Convergence of tuberculosis (TB) and HIV epidemics is associated with
      higher morbidity and mortality risks and understanding their distribution across
      key demographic factors is essential for prevention and control. This analysis
      examines the prevalence of TB, HIV and TB-HIV coinfection across age and gender
      in patients with presumptive TB seeking care at the National TB and Leprosy
      Training Center in Nigeria. METHODS: Samples from 1603 presumptive pulmonary TB
      cases who provided informed consent were evaluated with a sequential testing
      algorithm that included a smear microscopy, cultures in liquid and broth media
      and then genotyping by Hain line probe assays. HIV was serially tested with two
      HIV rapid assays and retested with a third assay in non-conclusive samples.
      RESULTS: Twenty-three percent (375/1603) had confirmed pulmonary TB infection,
      23.6% (378/1603) were positive for HIV infection and 26.9% (101/375) of the
      confirmed TB cases were HIV co-infected. Males had a higher prevalence of TB:
      27.6% vs. 18.0%, p < .0001; and a lower prevalence of HIV: 19.0% vs. 29.6%, p <
      .0001. In the age range of 25-29 years, males were twice as likely to have TB (OR
      = 2.2; 95% confidence interval [CI]: 1.3-3.9, p = 0.0032) while females were five
      times more likely to have HIV (OR = 4.8; 95% CI: 2.6-8.9, p < .0001). Persons
      with TB-HIV coinfection were more likely to be young, female and less likely to
      be married. CONCLUSION: Younger females with a high burden of HIV may be under
      diagnosed and under-reported for TB in Nigeria. Community programs for
      intensified and early detection of TB and HIV targeting younger females are
      needed in this setting.

PMID- 30192745
TI  - Comparing two classes of biological distribution systems using network analysis.
AB  - Distribution networks-from vasculature to urban transportation pathways-are
      spatially embedded networks that must route resources efficiently in the face of
      pressures induced by the costs of building and maintaining network
      infrastructure. Such requirements are thought to constrain the topological and
      spatial organization of these systems, but at the same time, different kinds of
      distribution networks may exhibit variable architectural features within those
      general constraints. In this study, we use methods from network science to
      compare and contrast two classes of biological transport networks: mycelial fungi
      and vasculature from the surface of rodent brains. These systems differ in terms
      of their growth and transport mechanisms, as well as the environments in which
      they typically exist. Though both types of networks have been studied
      independently, the goal of this study is to quantify similarities and differences
      in their network designs. We begin by characterizing the structural backbone of
      these systems with a collection of measures that assess various kinds of network
      organization across topological and spatial scales, ranging from measures of loop
      density, to those that quantify connected pathways between different network
      regions, and hierarchical organization. Most importantly, we next carry out a
      network analysis that directly considers the spatial embedding and properties
      especially relevant to the function of distribution systems. We find that
      although both the vasculature and mycelia are highly constrained planar networks,
      there are clear distinctions in how they balance tradeoffs in network measures of
      wiring length, efficiency, and robustness. While the vasculature appears well
      organized for low cost, but relatively high efficiency, the mycelia tend to form
      more expensive but in turn more robust networks. As a whole, this work
      demonstrates the utility of network-based methods to identify both common
      features and variations in the network structure of different classes of
      biological transport systems.

PMID- 30192748
TI  - Correction: Suppression of GATA-3 Nuclear Import and Phosphorylation: A Novel
      Mechanism of Corticosteroid Action in Allergic Disease.
AB  - [This corrects the article DOI: 10.1371/journal.pmed.1000076.].

PMID- 30192747
TI  - Nicotinamide-N-methyltransferase controls behavior, neurodegeneration and
      lifespan by regulating neuronal autophagy.
AB  - Nicotinamide N-methyl-transferase (NNMT) is an essential contributor to various
      metabolic and epigenetic processes, including the regulating of aging, cellular
      stress response, and body weight gain. Epidemiological studies show that NNMT is
      a risk factor for psychiatric diseases like schizophrenia and neurodegeneration,
      especially Parkinson's disease (PD), but its neuronal mechanisms of action remain
      obscure. Here, we describe the role of neuronal NNMT using C. elegans. We
      discovered that ANMT-1, the nematode NNMT ortholog, competes with the
      methyltransferase LCMT-1 for methyl groups from S-adenosyl methionine. Thereby,
      it regulates the catalytic capacities of LCMT-1, targeting NPRL-2, a regulator of
      autophagy. Autophagy is a core cellular, catabolic process for degrading
      cytoplasmic material, but very little is known about the regulation of autophagy
      during aging. We report an important role for NNMT in regulation of autophagy
      during aging, where high neuronal ANMT-1 activity induces autophagy via NPRL-2,
      which maintains neuronal function in old wild type animals and various disease
      models, also affecting longevity. In younger animals, however, ANMT-1 activity
      disturbs neuronal homeostasis and dopamine signaling, causing abnormal behavior.
      In summary, we provide fundamental insights into neuronal NNMT/ANMT-1 as pivotal
      regulator of behavior, neurodegeneration, and lifespan by controlling neuronal
      autophagy, potentially influencing PD and schizophrenia risk in humans.

PMID- 30192750
TI  - Developmental Eye Movement test and dyslexic children: A pilot study with eye
      movement recordings.
AB  - The goal of this study is to explore eye movement recordings during the
      Developmental Eye Movement (DEM) test in dyslexic and non-dyslexic children.
      Thirteen children with dyslexia, 13 non-dyslexic chronological age- and IQ
      matched children and 13 non-dyslexic reading age- and IQ-matched children were
      examined. Test C of the DEM test was performed with and without eye movement
      recordings (eye tracker by SuriCog). The results of the three groups were
      compared. Children with dyslexia and non-dyslexic children of equivalent reading
      age have significant longer fixation time and take longer to read Test C of the
      DEM test than non-dyslexic children of similar chronological age. A significant
      correlation was also found between the fixation time and the number of words read
      in one minute with the total time to read Test C of the DEM test. DEM test is a
      useful test for exploring the oculomotor behavior of dyslexic children during
      reading. The maturation of cortical structures controlling fixation capability
      appears to play a crucial role in reading skills.

PMID- 30192749
TI  - Impact of parental separation or divorce on school performance in preterm
      children: A population-based study.
AB  - The objective of this study was to quantify the possible decrease in school
      performance at five years of age in preterm children associated with parental
      separation or divorce, and to test whether this effect varies according to the
      child's age at the time of the separation. This study included 3,308 infants
      delivered at < 35 weeks of gestation born between 2003 and 2011 who were enrolled
      in the population-based LIFT cohort and who had an optimal neurodevelopmental
      outcome at two years of age. These infants were evaluated by their teachers to
      assess their abilities and behavior when they had reached five years of age,
      using the Global School Adaptation (GSA) questionnaire. The mean GSA score was
      50.8 points. Parental separations (assessed as parents either living together or
      living separately) were associated with a decrease in school performance at five
      years of age, although this was only the case for children who exhibited
      difficulties at school (3.7 points, p < 0.01). A decrease in school performance
      only occurred when parental separations took place between 3 and 5 years after
      the child's birth. Parental separation was associated with a decrease in these
      children's levels of motivation, autonomy, and manual dexterity. This study
      indicates that preterm infants of parents who had separated are particularly at
      risk of a lower scholar performance.

PMID- 30192751
TI  - Angiomyolipoma rebound tumor growth after discontinuation of everolimus in
      patients with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis.
AB  - INTRODUCTION: The EXIST-2 (NCT00790400) study demonstrated the superiority of
      everolimus over placebo for the treatment of renal angiomyolipomas associated
      with tuberous sclerosis complex (TSC) or sporadic lymphangioleiomyomatosis (LAM).
      This post hoc analysis of EXIST-2 study aimed to assess angiomyolipoma tumor
      behavior among patients who submitted to continued radiographic examination
      following discontinuation of everolimus in the noninterventional follow-up phase.
      METHODS: For patients who discontinued everolimus at the completion of extension
      phase for reasons other than angiomyolipoma progression, a single CT/MRI scan of
      the kidney was collected after 1 year of treatment discontinuation. Changes from
      baseline and from the time of everolimus discontinuation in the sum of volumes of
      target angiomyolipoma lesions were assessed in the non-interventional follow-up
      phase (data cutoff date, November 6, 2015). RESULTS: Of the 112 patients who
      received >=1 dose of everolimus and discontinued treatment by the end of
      extension phase, 34 (30.4%) were eligible for participation in the non
      interventional follow-up phase. Sixteen of 34 patients were evaluable for
      angiomyolipoma tumor behavior as they had at least one valid efficacy assessment
      (i.e. kidney CT/MRI scan) after everolimus discontinuation. During the non
      interventional follow-up phase, compared with baseline, two patients (12.5%)
      experienced angiomyolipoma progression (angiomyolipoma-related bleeding [n = 1],
      increased kidney volume [n = 1]). Five patients out of 16 (31.3%) experienced
      angiomyolipoma progression when compared with the angiomyolipoma tumor assessment
      at everolimus discontinuation. The median (range) percentage change in
      angiomyolipoma tumor volume (cm3) from baseline was -70.56 (-88.30; -49.64) at
      time of everolimus discontinuation (n = 11), and -50.55 (-79.40; -23.16) at week
      48 (n = 7) after discontinuation of everolimus. One patient death was reported
      due to angiomyolipoma hemorrhage. CONCLUSIONS: Angiomyolipoma lesions displayed
      an increase in volume following discontinuation of everolimus in patients with
      renal angiomyolipoma or sporadic LAM associated with TSC, but there was no
      evidence of rapid regrowth. TRIAL REGISTRATION: ClinicalTrials.gov NCT00790400.

PMID- 30192752
TI  - Over 2.5 million COI sequences in GenBank and growing.
AB  - The increasing popularity of cytochrome c oxidase subunit 1 (COI) DNA
      metabarcoding warrants a careful look at the underlying reference databases used
      to make high-throughput taxonomic assignments. The objectives of this study are
      to document trends and assess the future usability of COI records for metabarcode
      identification. The number of COI records deposited to the NCBI nucleotide
      database has increased by a geometric average of 51% per year, from 8,137 records
      deposited in 2003 to a cumulative total of ~ 2.5 million by the end of 2017.
      About half of these records are fully identified to the species rank, 92% are at
      least 500 bp in length, 74% have a country annotation, and 51% have latitude
      longitude annotations. To ensure the future usability of COI records in GenBank
      we suggest: 1) Improving the geographic representation of COI records, 2)
      Improving the cross-referencing of COI records in the Barcode of Life Data System
      and GenBank to facilitate consolidation and incorporation into existing
      bioinformatic pipelines, 3) Adherence to the minimum information about a marker
      gene sequence guidelines, and 4) Integrating metabarcodes from eDNA and mixed
      community studies with existing reference sequences. The growth of COI reference
      records over the past 15 years has been substantial and is likely to be a
      resource across many fields for years to come.

PMID- 30192753
TI  - Priming of leaf litter decomposition by algae seems of minor importance in
      natural streams during autumn.
AB  - Allochthonous detritus of terrestrial origin is one of the main energy sources in
      forested headwater streams, but its poor nutritional quality makes it difficult
      to use by heterotrophs. It has been suggested that algae growing on this detritus
      can enhance its nutritional quality and promote decomposition. So far, most
      evidence of this "priming effect" is derived from laboratory or mesocosm
      experiments, and its importance under natural conditions is unclear. We measured
      accrual of algae, phosphorus uptake capacity, and decomposition of poplar leaves
      in autumn in open- and closed-canopy reaches in 3 forest and 3 agricultural
      streams. Chlorophyll a abundance did not change significantly with stream type or
      with canopy cover, although in some agricultural streams it was higher in open
      than in closed canopy reaches. Canopy cover did not affect either phosphate
      uptake capacity or microbial decomposition. On the other hand, although there was
      no effect of canopy cover on invertebrate fragmentation rate, a significant
      interaction between canopy cover and stream suggests priming occurs at least in
      some streams. Overall, the results point to a weak or no priming effect of algae
      on litter decomposition in natural streams during autumn.

PMID- 30192754
TI  - Virtual screening using covalent docking to find activators for G245S mutant p53.
AB  - TP53 is the most mutated gene in all cancers. The mutant protein also accumulates
      in cells. The high frequency of p53 mutations makes the protein a promising
      target for anti-cancer therapy. Only a few molecules have been found, using in
      vitro screening, to reactivate the mutant protein. APR-246 is currently the most
      successful mutant p53 activator, which reactivates the transcriptional activity
      of p53 by covalently binding to C124 of the protein. We have recently created in
      silico models of G245S-mp53 in its apo and DNA-bound forms. In this paper we
      further report on our in silico screening for potential activators of G245S-mp53.
      We filtered the ZINC15 database (13 million compounds) to only include drug-like
      molecules with moderate to standard reactivity. Our filtered database of 130,000
      compounds was screened using the DOCKTITE protocol in the Molecular Operating
      Environment software. We performed covalent docking at C124 of G245S-mp53 to
      identify potential activators of the mutant protein. The docked compounds were
      ranked using a consensus scoring approach. We also used ADMET PredictorTM to
      predict pharmacokinetics and the possible toxicities of the compounds. Our
      screening procedure has identified compounds, mostly thiosemicarbazones and halo
      carbonyls, with the best potential as G245S-mp53 activators, which are described
      in this work. Based on its binding scores and ADMET risk score, compound 2 is
      likely to have the best potential as a G245S-mp53 activator compared to the other
      top hits.

PMID- 30192755
TI  - Molecular epidemiology of enteroviruses in young children at increased risk of
      type 1 diabetes.
AB  - BACKGROUND: Young children are susceptible to enterovirus (EV) infections, which
      cause significant morbidity in this age group. However, the current knowledge
      regarding the epidemiology of EVs and the circulating virus strains is mostly
      based on viruses detected in children with severe diseases leading to contact
      with the health care system, while the vast reservoir of EVs that circulate in
      the general population is less characterized. METHODOLOGY: The present study
      investigates the types and the prevalence of EVs circulating in the young
      children of the background population in Georgia, Colorado, and Washington State
      in the USA, and Germany, Sweden, and Finland in Europe. A total of 4018 stool
      samples, collected monthly from 300 healthy and non-hospitalized children at the
      age of 3-18 months in 2005-2009, were analyzed for the presence of EVs using RT
      PCR, followed by sequencing of the VP1-2A region of the viral genome to type the
      EV(s) present. All of the children carried type HLA-DQ2 or -DQ8 alleles
      associated with type 1 diabetes. PRINCIPAL FINDINGS: Altogether 201 children
      (67%) were found to be EV positive. The prevalence was much lower in Finnish
      children (26%) than in the children of the other counties combined (75%).
      Infections increased by age and showed a nadir during the winter months. Children
      who carried both the HLA-DQ2 and -DQ8 alleles had less infections than children
      who were homozygous for these alleles. Coxsackieviruses type A were the most
      frequently detected viruses in all geographical regions. Coxsackievirus type A4,
      Echovirus type 18, and Echovirus type 25 were shed for longer time periods than
      the other EV types. CONCLUSIONS: Compared to prevalence data from symptomatic
      patients requiring medical attention, this study provides a better view of EVs
      circulating in young children in the USA and in Europe. The observations may
      prove useful for the selection of strategies for designing EV vaccines in the
      future. The study also confirms our previous serological findings suggesting that
      EV infections are relatively rare in Finland.

PMID- 30192756
TI  - Human personality reflects spatio-temporal and time-frequency EEG structure.
AB  - The reliable and objective assessment of intelligence and personality has been a
      topic of increasing interest of contemporary neuroscience and psychology. It is
      known that intelligence can be measured by estimating the mental speed or
      velocity of information processing. This is usually measured as a reaction time
      during elementary cognitive task processing, while personality is often assessed
      by means of questionnaires. On the other hand, human personality affects the way
      a subject accomplishes elementary cognitive tasks and, therefore, some
      personality features can define intelligence. It is expected that these features,
      as well as mental abilities in performing cognitive tasks are associated with the
      brain's electrical neural activity. Although several studies reported correlation
      between event-related potentials, mental ability and intelligence, there is a
      lack of information about time-frequency and spatio-temporal structures of neural
      activity which characterize this relation. In the present work, we analyzed human
      electroencephalograms (EEG) recorded during the performance of elementary
      cognitive tasks using the Schulte test, which is a paper-pencil based instrument
      for assessing elementary cognitive ability or mental speed. According to
      particular features found of the EEG structure, we divided the subjects into
      three groups. For subjects in each group, we applied the Sixteen Personality
      Factor Questionnaire (16PF) to assess the their personality traits. We
      demonstrated that each group exhibited a different score on the personality
      scale, such as warmth, reasoning, emotional stability and dominance. Summing up,
      we found a link between EEG features, mental abilities and personality traits.
      The obtained results can be of great interest for testing human personality to
      create automatized intelligent programs which combine simple tests and EEG
      measurements for real estimation of human personality traits and mental
      abilities.

PMID- 30192757
TI  - Extensive recoding of dengue virus type 2 specifically reduces replication in
      primate cells without gain-of-function in Aedes aegypti mosquitoes.
AB  - Dengue virus (DENV), an arthropod-borne ("arbovirus") virus, causes a range of
      human maladies ranging from self-limiting dengue fever to the life-threatening
      dengue shock syndrome and proliferates well in two different taxa of the Animal
      Kingdom, mosquitoes and primates. Mosquitoes and primates show taxonomic group
      specific intolerance to certain codon pairs when expressing their genes by
      translation. This is called "codon pair bias". By necessity, dengue viruses
      evolved to delicately balance this fundamental difference in their open reading
      frames (ORFs). We have undone the evolutionarily conserved genomic balance in the
      DENV2 ORF sequence and specifically shifted the encoding preference away from
      primates. However, this recoding of DENV2 raised concerns of 'gain-of-function,'
      namely whether recoding could inadvertently increase fitness for replication in
      the arthropod vector. Using mosquito cell lines and two strains of Aedes aegypti
      we did not observe any increase in fitness in DENV2 variants codon pair
      deoptimized for humans. This ability to disrupt and control DENV2's host
      preference has great promise towards developing the next generation of synthetic
      vaccines not only for DENV but for other emerging arboviral pathogens such as
      chikungunya virus and Zika virus.

PMID- 30192758
TI  - Combining in vivo and in vitro biomechanical data reveals key roles of
      perivascular tethering in central artery function.
AB  - Considerable insight into effectors of cardiovascular function can be gleaned
      from controlled studies on mice, especially given the diverse models that are
      available. Toward this end, however, there is a need for consistent and
      complementary methods of in vivo and in vitro data analysis, synthesis, and
      interpretation. The overall objective of this study is twofold. First, we present
      new semi-automated methods to quantify in vivo measurements of vascular function
      in anesthetized mice as well as new approaches to synthesize these data with
      those from in vitro biaxial mechanical characterizations. Second, we contrast
      regional differences in biomechanical behaviors along the central vasculature by
      combining biaxial strains measured in vivo with data on the unloaded geometry and
      biaxial material properties measured in vitro. Results support the hypothesis
      that the healthy ascending aorta stores significant elastic energy during
      systole, which is available to work on the heart and blood during diastole,
      particularly during periods of physical exertion, and further suggest that
      perivascular tethering allows arteries to work at lower values of wall stress and
      material stiffness than often assumed. The numerous measurements of vascular
      function and properties provided herein can also serve as reference values for
      normal wild-type male and female mice, to which values for myriad genetic,
      surgical, and pharmacological models can be compared in future studies.

PMID- 30192759
TI  - A new design for the review and appraisal of semi-solid dosage forms: Semi-solid
      Control Diagram (SSCD).
AB  - The Semi-solid Control Diagram (SSCD) is a new tool designed for the study of
      different excipients and different semi-solid dosage forms. It can be used to
      review and evaluate different formulations and/or batches and facilitate the
      selection of one of them that will present the most suitable galenic
      characteristics for topical application. It is also useful to track stability
      studies by comparing the diagrams, which allows to measure the impact of
      subjecting the formulation to different conditions and times to be examined. In
      this study, the Semi-solid Control Diagram (SSCD) is used as an instrument for
      studying and evaluating semi-solid pharmaceutical dosage forms, by comparing
      several different semisolid preparations (lipogels). With these results, the tool
      is validated and the best formulation has been discriminated from the others.

PMID- 30192760
TI  - Prioritizing conserved areas threatened by wildfire and fragmentation for
      monitoring and management.
AB  - In many parts of the world, the combined effects of habitat fragmentation and
      altered disturbance regimes pose a significant threat to biodiversity. This is
      particularly true in Mediterranean-type ecosystems (MTEs), which tend to be fire
      prone, species rich, and heavily impacted by human land use. Given the spatial
      complexity of overlapping threats and species' vulnerability along with limited
      conservation budgets, methods are needed for prioritizing areas for monitoring
      and management in these regions. We developed a multi-criteria Pareto ranking
      methodology for prioritizing spatial units for conservation and applied it to
      fire threat, habitat fragmentation threat, species richness, and genetic
      biodiversity criteria in San Diego County, California, USA. We summarized the
      criteria and Pareto ranking results (from west to east) within the maritime,
      coastal, transitional, inland climate zones within San Diego County. Fire threat
      increased from the maritime zone eastward to the transitional zone, then
      decreased in the mountainous inland climate zone. Number of fires and fire return
      interval departure were strongly negatively correlated. Fragmentation threats,
      particularly road density and development density, were highest in the maritime
      climate zone, declined towards the east, and were positively correlated. Species
      richness criteria showed distributions among climate zones similar to those of
      the fire threat variables. When using species richness and fire threat criteria,
      most lower-ranked (higher conservation priority) units occurred in the coastal
      and transitional zones. When considering genetic biodiversity, lower-ranked units
      occurred more often in the mountainous inland zone. With Pareto ranking, there is
      no need to select criteria weights as part of the decision-making process.
      However, negative correlations and larger numbers of criteria can result in more
      units assigned to the same rank. Pareto ranking is broadly applicable and can be
      used as a standalone decision analysis method or in conjunction with other
      methods.

PMID- 30192761
TI  - In search of the Goldilocks zone for hybrid speciation.
AB  - Hybridization has recently gained considerable interest both as a unique
      opportunity for observing speciation mechanisms and as a potential engine for
      speciation. The latter remains a controversial topic. It was recently
      hypothesized that the reciprocal sorting of genetic incompatibilities from
      parental species could result in hybrid speciation, when the hybrid population
      maintains a mixed combination of the parental incompatibilities that prevents
      further gene exchange with both parental populations. However, the specifics of
      the purging/sorting process of multiple incompatibilities have not been examined
      theoretically. We here investigate the allele-frequency dynamics of an isolated
      hybrid population that results from a single hybridization event. Using models of
      two or four loci, we investigate the fate of one or two genetic incompatibilities
      of the Dobzhansky-Muller type (DMIs). We study how various parameters affect both
      the sorting/purging of the DMIs and the probability of observing hybrid
      speciation by reciprocal sorting. We find that the probability of hybrid
      speciation is strongly dependent on the linkage architecture (i.e. the order and
      recombination rate between loci along chromosomes), the population size of the
      hybrid population, and the initial relative contributions of the parental
      populations to the hybrid population. We identify a Goldilocks zone for specific
      linkage architectures and intermediate recombination rates, in which hybrid
      speciation becomes highly probable. Whereas an equal contribution of parental
      populations to the hybrid population maximizes the hybrid speciation probability
      in the Goldilocks zone, other linkage architectures yield unintuitive asymmetric
      maxima. We provide an explanation for this pattern, and discuss our results both
      with respect to the best conditions for observing hybrid speciation in nature and
      their implications regarding patterns of introgression in hybrid zones.

PMID- 30192762
TI  - Hunchback is counter-repressed to regulate even-skipped stripe 2 expression in
      Drosophila embryos.
AB  - Hunchback is a bifunctional transcription factor that can activate and repress
      gene expression in Drosophila development. We investigated the regulatory DNA
      sequence features that control Hunchback function by perturbing enhancers for one
      of its target genes, even-skipped (eve). While Hunchback directly represses the
      eve stripe 3+7 enhancer, we found that in the eve stripe 2+7 enhancer, Hunchback
      repression is prevented by nearby sequences-this phenomenon is called counter
      repression. We also found evidence that Caudal binding sites are responsible for
      counter-repression, and that this interaction may be a conserved feature of eve
      stripe 2 enhancers. Our results alter the textbook view of eve stripe 2
      regulation wherein Hb is described as a direct activator. Instead, to generate
      stripe 2, Hunchback repression must be counteracted. We discuss how counter
      repression may influence eve stripe 2 regulation and evolution.

PMID- 30192764
TI  - Multi-year data from satellite- and ground-based sensors show details and scale
      matter in assessing climate's effects on wetland surface water, amphibians, and
      landscape conditions.
AB  - Long-term, interdisciplinary studies of relations between climate and ecological
      conditions on wetland-upland landscapes have been lacking, especially studies
      integrated across scales meaningful for adaptive resource management. We
      collected data in situ at individual wetlands, and via satellite for surrounding
      4-km2 landscape blocks, to assess relations between annual weather dynamics, snow
      duration, phenology, wetland surface-water availability, amphibian presence and
      calling activity, greenness, and evapotranspiration in four U.S. conservation
      areas from 2008 to 2012. Amid recent decades of relatively warm growing seasons,
      2012 and 2010 were the first and second warmest seasons, respectively, dating
      back to 1895. Accordingly, we observed the earliest starts of springtime
      biological activity during those two years. In all years, early-season amphibians
      first called soon after daily mean air temperatures were >= 0 degrees C and snow
      had mostly melted. Similarly, satellite-based indicators suggested seasonal leaf
      out happened soon after snowmelt and temperature thresholds for plant growth had
      occurred. Daily fluctuations in weather and water levels were related to
      amphibian calling activity, including decoupling the timing of the onset of
      calling at the start of season from the onset of calling events later in the
      season. Within-season variation in temperature and precipitation also was related
      to vegetation greenness and evapotranspiration, but more at monthly and seasonal
      scales. Wetland water levels were moderately to strongly associated with
      precipitation and early or intermittent wetland drying likely reduced amphibian
      reproduction success in some years, even though Pseudacris crucifer occupied
      sites at consistently high levels. Notably, satellite-based indicators of
      landscape water availability did not suggest such consequential, intra-seasonal
      variability in wetland surface-water availability. Our cross-disciplinary data
      show how temperature and precipitation interacted to affect key ecological
      relations and outcomes on our study landscapes. These results demonstrate the
      value of multi-year studies and the importance of scale for understanding actual
      climate-related effects in these areas.

PMID- 30192763
TI  - Exploring the knowledge, explanatory models of illness, and patterns of
      healthcare-seeking behaviour of Fang culture-bound syndromes in Equatorial
      Guinea.
AB  - In 1994, the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV)
      included "culture-bound syndromes" in its classification of psychiatric disorders
      and associated them with disease processes that manifest in behavioural or
      thought disorders that develop within a given cultural context. This study
      examines the definitions, explanatory models, signs and symptoms, and healthcare
      seeking behaviours common to Fang culture-bound syndromes (i.e., kong, eluma,
      witchcraft, mibili, mikug, and nsamadalu). The Fang ethnic group is the majority
      ethnic group in Equatorial Guinea. From September 2012 to January 2013, 45 key
      Fang informants were selected, including community leaders, tribal elders,
      healthcare workers, traditional healers, and non-Catholic pastors in 39 of 724
      Fang tribal villages in 6 of 13 districts in the mainland region of Equatorial
      Guinea. An ethnographic approach with an emic-etic perspective was employed. Data
      were collected using semi-structured interviews, participant observation and a
      questionnaire that included DHS6 key indicators. Interviews were designed based
      on the Cultural Formulation form in the DSM-5 and explored the definition of Fang
      cultural syndromes, symptoms, cultural perceptions of cause, and current help
      seeking. Participants defined "Fang culture-bound syndromes" as those diseases
      that cannot be cured, treated, or diagnosed by science. Such syndromes present
      with the same signs and symptoms as diseases identified by Western medicine.
      However, they arise because of the actions of enemies, because of the actions of
      spirits or ancestors, as punishments for disregarding the law of God, because of
      the violation of sexual or dietary taboos, or because of the violation of a Fang
      rite of passage, the dzas, which is celebrated at birth. Six Fang culture-bound
      syndromes were included in the study: 1) Eluma, a disease that is targeted at the
      victim out of envy and starts out with sharp, intense, focussed pain and
      aggressiveness; 2) Witchcraft, characterized by isolation from the outside,
      socially maladaptive behaviour, and the use of hallucinogenic substances; 3)
      Kong, which is common among the wealthy class and manifests as a disconnection
      from the environment and a lack of vital energy; 4) Mibili, a possession by evil
      spirits that manifests through visual and auditory hallucinations; 5) Mikug,
      which appears after a person has had contact with human bones in a ritual; and 6)
      Nsamadalu, which emerges after a traumatic process caused by violating traditions
      through having sexual relations with one's sister or brother. The therapeutic
      resources of choice for addressing Fang culture-bound syndromes were traditional
      Fang medicine and the religious practices of the Bethany and Pentecostal
      churches, among others. Among African ethnic groups, symbolism, the weight of
      tradition, and the principle of chance in health and disease are underlying
      factors in the presentation of certain diseases, which in ethno-psychiatry are
      now referred to as culture-bound syndromes. In this study, traditional healers,
      elders, healthcare professionals, religious figures, and leaders of the Fang
      community in Equatorial Guinea referred to six such cultural syndromes: eluma,
      witchcraft, kong, mibili, mikug, and nsamadalu. In the absence of a
      multidisciplinary approach to mental illness in the country, the Fang ethnic
      group seeks healthcare for culture-bound syndromes from traditional healing and
      religious rites in the Evangelical faiths.

PMID- 30192765
TI  - Efficiency of HIV services in Nigeria: Determinants of unit cost variation of HIV
      counseling and testing and prevention of mother-to-child transmission
      interventions.
AB  - BACKGROUND: Like most countries with a substantial HIV burden, Nigeria continues
      to face challenges in reaching coverage targets of HIV services. A fundamental
      problem is stagnated funding in recent years. Improving efficiency is therefore
      paramount to effectively scale-up HIV services. In this study, we estimated the
      facility-level average costs (or unit costs) of HIV Counseling and Testing (HCT)
      and Prevention of Mother-to-Child Transmission (PMTCT) services and characterized
      determinants of unit cost variation. We investigated the role of service delivery
      modalities and the link between facility-level management practices and unit cost
      variability along both services' cascades. METHODS: We conducted a cross
      sectional, observational, micro-costing study in Nigeria between December 2014
      and May 2015 in 141 HCT, and 137 PMTCT facilities, respectively. We
      retrospectively collected relevant input quantities (personnel, supplies,
      utilities, capital, and training), input prices, and output data for the year
      2013. Staff costs were adjusted using time-motion methods. We estimated the
      facility-level average cost per service along the HCT and PMTCT service cascades
      and analyzed their composition and variability. Through linear regressions
      analysis, we identified aspects of service delivery and management practices
      associated with unit costs variations. RESULTS: The weighted average cost per HIV
      positive client diagnosed through HCT services was US$130. The weighted average
      cost per HIV-positive woman on prophylaxis in PMTCT services was US$858. These
      weighted values are estimates of nationally representative unit costs in Nigeria.
      For HCT, the facility-level unit costs per client tested and per HIV-positive
      client diagnosed were US$30 and US$1,364, respectively; and the median unit costs
      were US$17 and US$245 respectively. For PMTCT, the facility-level unit costs per
      woman tested, per HIV-positive woman diagnosed, and per HIV-positive woman on
      prophylaxis were US$46, US$2,932, and US$3,647, respectively, and the median unit
      costs were US$24, US$1,013 and US$1,448, respectively. Variability in costs
      across facilities was principally explained by the number of patients,
      integration of HIV services, task shifting, and the level of care. DISCUSSION:
      Our findings demonstrate variability in unit costs across facilities. We found
      evidence consistent with economies of scale and scope, and efficiency gains in
      facilities implementing task-shifting. Our results could inform program design by
      suggesting ways to improve resource allocation and efficiently scale-up the HIV
      response in Nigeria. Some of our findings might also be relevant for other
      settings.

PMID- 30192766
TI  - Laser microtextured titanium implant surfaces reduce in vitro and in situ oral
      biofilm formation.
AB  - INTRODUCTION: Micro- or nano-topography can both provide antimicrobial properties
      and improve osseointegration of dental implant titanium surfaces. Laser treatment
      is one of the best surface microtexturing techniques. The aim of this study was
      to evaluate in vitro and in situ biofilm formation on a laser-treated titanium
      surface, comparing it with two conventional surfaces, machined and grit-blasted.
      METHODS: For the in vitro experiment, an oral microcosm biofilm model was
      developed on the surface of titanium disks and reference human enamel using a
      bioreactor for 48 h. For the in situ experiment, titanium implants with laser
      treated, machined and grit-blasted surfaces were mounted on intraoral trays and
      worn by ten volunteers for 48 h. Biofilm formation was quantitatively evaluated,
      and surfaces were analyzed using confocal laser scanning microscopy, scanning
      electron microscopy and energy-dispersive X-ray spectroscopy. RESULTS-IN VITRO
      STUDY: Biofilm structures with a prevalence of viable cells covered most of the
      machined, grit-blasted and human enamel surfaces, whereas less dense biofilm
      structures with non-confluent microcolonies were observed on the laser-treated
      titanium. Laser-treated titanium showed the lowest biofilm formation, where
      microorganisms colonized the edges of the laser-created pits, with very few or no
      biofilm formation observed inside the pits. RESULTS-IN SITU STUDY: The biofilm
      formation pattern observed was similar to that in the in vitro experiment.
      Confocal laser scanning microscopy showed complete coverage of the implant
      threads, with mostly viable cells in grit-blasted and machined specimens.
      Unexpectedly, laser-treated specimens showed few dead microbial cells colonizing
      the bottom of the threads, while an intense colonization was found on the
      threading sides. CONCLUSION: This data suggests that laser-created
      microtopography can reduce biofilm formation, with a maximum effect when the
      surface is blasted orthogonally by the laser beam. In this sense the orientation
      of the laser beam seems to be relevant for the biological interaction with
      biofilms.

PMID- 30192768
TI  - Social space and alcohol use initiation among youth in northern Tanzania.
AB  - INTRODUCTION: Alcohol use is a key risk factor for disease worldwide. Consumption
      of alcohol is increasing in sub Saharan Africa, where youth are already at high
      risk of HIV due to its high prevalence in the region. Studies show that youth
      begin drinking alcohol early; however, there is a need to further explore the
      initiation of alcohol use in order to design appropriate interventions in this
      population. METHODS: We conducted a qualitative study with youth in Mwanza and
      Kilimanjaro regions in Tanzania to explore alcohol consumption among youth.
      Participants were a purposive sample of youth aged 15-24 composed of secondary
      school and college students, and formal and informal sector employees. We
      conducted 35 in-depth interviews using a semi-structured guide to understand
      youth's personal experiences with alcohol consumption. Two social scientists
      conducted a multi stage, inductive analysis of the data. FINDINGS: Alcohol
      consumption was reported to mainly start during adolescence, although in some
      cases it started as early as at 10 years of age. Young women reported drinking
      less, and initiated drinking later compared to males. Social space assumed a
      primary role in alcohol initiation. The social environment and influence of
      important social actors were key aspects of youth's social space. Youth reported
      starting to consume alcohol at home, social events and in stressful environments
      with key influencers being parents, relatives, peers and intimate partners.
      CONCLUSIONS: Our findings show that the social space (social environment and
      interactions) plays an important role in influencing youth initial consumption of
      alcohol. Interventions addressing alcohol initiation among the population need to
      address the social spaces where initiation takes place and engage the significant
      actors in these spaces. There is need to further explore underlying societal
      drinking norms to better understand how they shape social environments and young
      people's initiation of alcohol use.

PMID- 30192767
TI  - Speed-accuracy tradeoffs in human speech production.
AB  - Speech motor actions are performed quickly, while simultaneously maintaining a
      high degree of accuracy. Are speed and accuracy in conflict during speech
      production? Speed-accuracy tradeoffs have been shown in many domains of human
      motor action, but have not been directly examined in the domain of speech
      production. The present work seeks evidence for Fitts' law, a rigorous
      formulation of this fundamental tradeoff, in speech articulation kinematics by
      analyzing USC-TIMIT, a real-time magnetic resonance imaging data set of speech
      production. A theoretical framework for considering Fitts' law with respect to
      models of speech motor control is elucidated. Methodological challenges in
      seeking relationships consistent with Fitts' law are addressed, including the
      operational definitions and measurement of key variables in real-time MRI data.
      Results suggest the presence of speed-accuracy tradeoffs for certain types of
      speech production actions, with wide variability across syllable position, and
      substantial variability also across subjects. Coda consonant targets immediately
      following the syllabic nucleus show the strongest evidence of this tradeoff, with
      correlations as high as 0.72 between speed and accuracy. A discussion is provided
      concerning the potentially limited applicability of Fitts' law in the context of
      speech production, as well as the theoretical context for interpreting the
      results.

PMID- 30192769
TI  - Routinely measured hematological parameters and prediction of recurrent vascular
      events in patients with clinically manifest vascular disease.
AB  - BACKGROUND AND AIMS: The predictive value of traditional risk factors for
      vascular events in patients with manifest vascular disease is limited,
      underscoring the need for novel biomarkers to improve risk stratification. Since
      hematological parameters are routinely assessed in clinical practice, they are
      readily available candidates. METHODS: We used data from 3,922 vascular patients,
      who participated in the Second Manifestations of ARTerial Disease (SMART) study.
      We first investigated associations between recurrent vascular events and 22
      hematological parameters, obtained from the Utrecht Patient Oriented Database
      (UPOD), and then assessed whether parameters associated with outcome improved
      risk prediction. RESULTS: After adjustment for all SMART risk score (SRS)
      variables, lymphocyte %, neutrophil count, neutrophil % and red cell distribution
      width (RDW) were significantly associated with vascular events. When individually
      added to the SRS, lymphocyte % improved prediction of recurrent vascular events
      with a continuous net reclassification improvement (cNRI) of 17.4% [95% CI: 2.1,
      32.1%] and an increase in c-statistic of 0.011 [0.000, 0.022]. The combination of
      lymphocyte % and neutrophil count resulted in a cNRI of 22.2% [3.2, 33.4%] and
      improved c-statistic by 0.011 [95% CI: 0.000, 0.022]. Lymphocyte % and RDW
      yielded a cNRI of 18.7% [3.3, 31.9%] and improved c-statistic by 0.016 [0.004,
      0.028]. However, the addition of hematological parameters only modestly increased
      risk estimates for patients with an event during follow-up. CONCLUSIONS: Several
      hematological parameters were independently associated with recurrent vascular
      events. Lymphocyte % alone and in combination with other parameters enhanced
      discrimination and reclassification. However, the incremental value for patients
      with a recurrent event was limited.

PMID- 30192770
TI  - Predictors of residual antimalarial drugs in the blood in community surveys in
      Tanzania.
AB  - BACKGROUND: Understanding pattern of antimalarials use at large scale helps
      ensuring appropriate use of treatments and preventing the spread of resistant
      parasites. We estimated the proportion of individuals in community surveys with
      residual antimalarials in their blood and identified the factors associated with
      the presence of the most commonly detected drugs, lumefantrine and/or desbutyl
      lumefantrine (LF/DLF) or sulfadoxine-pyrimethamine (SP). METHODS: A cross
      sectional survey was conducted in 2015 in three regions of Tanzania with
      different levels of malaria endemicity. Interviews were conducted and blood
      samples collected through household surveys for further antimalarial measurements
      using liquid chromatography coupled to tandem mass spectrometry. In addition,
      diagnosis and treatment availability was investigated through outlet surveys.
      Multilevel mixed effects logistic regression models were used to estimate odds
      ratios for having LF/DLF or SP in the blood. RESULTS: Amongst 6391 participants,
      12.4% (792/6391) had LF/DLF and 8.0% (510/6391) SP in the blood. Factors
      associated with higher odds of detecting LF/DLF in the blood included fever in
      the previous two weeks (OR = 2.6, p<0.001), living in districts of higher malaria
      prevalence (OR = 1.5, p<0.001) and living in a ward in which all visited drug
      stores had artemisinin-based combination therapies in stocks (OR = 2.7, p =
      0.020). Participants in older age groups were less likely to have LF/DLF in the
      blood (OR = 0.9, p<0.001). Factors associated with higher odds of having SP in
      the blood included being pregnant (OR = 4.6, p<0.001), living in Mwanza (OR =
      3.9, p<0.001 compared to Mbeya), fever in the previous two weeks (OR = 1.7,
      p<0.001) and belonging to older age groups (OR = 1.2, p<0.001). CONCLUSION: The
      most significant predictors identified were expected. History of fever in the
      past two weeks and young age were significant predictors of LF/DLF in the blood,
      which is encouraging. Antimalarial drug pressure was high and hence the use of
      recommended first-line drugs in combination with malaria Rapid Diagnostics Tests
      should be promoted to ensure appropriate treatment.

PMID- 30192771
TI  - Indexing dialysis dose for gender, body size and physical activity: Impact on
      survival.
AB  - Current practice basing dialysis dose on urea distribution volume (V) has been
      questioned. We explored the impact on survival of scaling dialysis dose (Kt) to
      parameters reflective of metabolic activity. In a multicentre prospective cohort
      study of 1500 patients on thrice-weekly haemodialysis, body surface area (BSA)
      and resting energy expenditure (REE) were estimated using validated equations and
      physical activity by the Recent Physical Activity Questionnaire. Total energy
      expenditure (TEE) was estimated from REE and physical activity data. Kt was
      calculated from delivered (single-pool Kt/V)*Watson V. Kt/BSA, Kt/REE and Kt/TEE
      were then calculated at baseline and 6 monthly during follow-up for 2 years. In
      adjusted Cox models Kt/TEE, Kt/BSA, Kt/REE, in that order, had lower hazard
      ratios for death than single-pool Kt/V. On the basis of adjusted survival
      differences, putative minimum target doses were estimated for Kt/BSA as 27119
      ml/m2 and Kt/TEE as 25.79 ml/kcal. We identified spKt/V values equivalent to
      these estimated targets, ranging from 1.4 to 1.8 in patient groups based on
      gender, body size and physical activity. For sedentary patients, the minimum
      target dose was 1.4 for large males, 1.5 for small males and 1.7 for women. For
      active patients the target was 1.8 irrespective of gender and body-weight.
      Patients achieving these individualised minimum targets had greater adjusted two
      year survival compared to those achieving conventional minimum targets. Metabolic
      activity related parameters, such as Kt/TEE and Kt/BSA, may have a clinically
      important role in scaling haemodialysis dose. Using such parameters or their
      spKt/V equivalents to adjust minimum target doses based on gender, body size and
      habitual physical activity may have a positive impact on survival.

PMID- 30192772
TI  - Continued occurrence of serotype 1 pneumococcal meningitis in two regions located
      in the meningitis belt in Ghana five years after introduction of 13-valent
      pneumococcal conjugate vaccine.
AB  - BACKGROUND: Increases in pneumococcal meningitis were reported from Ghanaian
      regions that lie in the meningitis belt in 2016-2017, despite introduction of 13
      valent pneumococcal conjugate vaccine (PCV13) in 2012 using a 3-dose schedule (6,
      10, and 14 weeks). We describe pneumococcal meningitis epidemiology in the
      Ghanaian Northern and Upper West regions across two meningitis seasons. METHODS:
      Suspected meningitis cases were identified using World Health Organization
      standard definitions. Pneumococcal meningitis was confirmed if pneumococcus was
      the sole pathogen detected by polymerase chain reaction, culture, or latex
      agglutination in cerebrospinal fluid collected from a person with suspected
      meningitis during December 2015-March 2017. Pneumococcal serotyping was done
      using PCR. Annual age-specific pneumococcal meningitis incidence (cases per
      100,000 population) was calculated, adjusting for suspected meningitis cases
      lacking confirmatory testing. FINDINGS: Among 153 pneumococcal meningitis cases,
      137 (89.5%) were serotyped; 100 (73.0%) were PCV13-type, including 85 (62.0%)
      that were serotype 1, a PCV13-targeted serotype. Persons aged >=5 years accounted
      for 96.7% (148/153) of cases. Comparing 2015-2016 and 2016-2017 seasons, the
      proportion of non-serotype 1 PCV13-type cases decreased from 20.0% (9/45) to 4.1%
      (3/74) (p = 0.008), whereas the proportion that was serotype 1 was stable (71.1%
      (32/45) vs. 58.1% (43/74); p = 0.16). Estimated adjusted pneumococcal meningitis
      incidence was 1.8 in children aged <5 years and ranged from 6.8-10.5 in older
      children and adults. CONCLUSIONS: High pneumococcal meningitis incidence with a
      large proportion of serotype 1 disease in older children and adults suggests
      infant PCV13 vaccination has not induced herd protection with this schedule in
      this high-transmission setting.

PMID- 30192773
TI  - The effect of genotype and traditional food processing methods on in-vitro
      protein digestibility and micronutrient profile of sorghum cooked products.
AB  - Sorghum (Sorghum bicolor (L.) Moench) is one of the principal staple for millions
      of people in sub-Saharan Africa serving as the main sources of protein. However,
      protein digestibility is low in sorghum and this may be affected by processing
      methods. In this study 15 sorghum cultivars and one variety each of maize (Zea
      maize) and tef (Eragrostis tef) all of Ethiopian origin were investigated for in
      vitro protein digestibility (IVPD), activity and concentration of anti
      nutritional factors and micro nutrient profile in raw flour and various cooked
      food samples. Kafirin composition content and composition was also determined
      from raw flour samples of the sorghum cultivars. IVPD was significantly different
      between genotypes with both maize and tef superior to sorghum both in cooked and
      uncooked state except for the high lysine genotype Wetet Be-gunchie. Cooking
      significantly reduced IVPD in all crops but had only minor effect in maize.
      Results revealed a highly significant interaction between genotype and food
      processing methods where, occasionally, genotypes with highest IVPD under one
      processing method ended up to be the lowest under another. Trypsin inhibitor
      levels had a significant and negative correlation with IVPD (r2 = 0.1), while
      changes in phytic acid concentration and intrinsic phytase levels during
      processing followed opposite trends to each other. Processing increased mineral
      levels by 20-44% for iron and 4-29% for zinc perhaps due to degradation of phytic
      acid. Results demonstrated that protein digestibility and the concentration of
      anti- nutritional factors varied widely depending on the food type.
      Identification of specific genotypes for a specific food product may help improve
      the nutritional quality of sorghum based foods.

PMID- 30192774
TI  - Pulmonary effects of repeated six-hour normoxic and hyperoxic dives.
AB  - This study examines differential effects of immersion, elevated oxygen partial
      pressure, and exercise on pulmonary function after series of five daily six-hour
      dives at 130 kPa (1.3 ATA), with 18 hours between dives. Five cohorts of 10 to 14
      divers participated. The exposure phases were resting while breathing O2 or air
      in the water ("wetO2", "wetAir") or O2 in the hyperbaric chamber ("dryO2"), and
      exercise in the water while breathing O2 or air ("wetO2X", "wetAirX").
      Respiratory symptoms were recorded during and after each dive, and pulmonary
      function (forced flow-volume) was measured twice at baseline before diving, after
      each dive both immediately and on the following morning, and three days post
      diving ("Day+3"). The incidences of symptoms and of flow volume changes from
      baseline greater than normal limits ("DeltaFV") were assessed, as were mean
      DeltaFV. The parameters examined were forced vital capacity (FVC), forced expired
      volume in 1 second (FEV1), and forced expired flow from 25% to 75% volume expired
      (FEF25-75). The phases ranked from greatest to least fraction of diver-days with
      symptoms were wetO2X (56%) > dryO2 (42%) > wetO2 (13%) > [wetAir (2%) or wetAirX
      (1%)] (p<0.05). FEV1 and FEF25-75 were depressed in the morning following wetO2
      and wetO2X and on Day+3 after and wetO2X, but increased immediately following
      each wetAirX dive. O2 exposures caused symptoms and DeltaFV suggestive of
      pulmonary oxygen toxicity,exacerbated by exercise. Indices of small airway
      function showed late (17-hour) post-O2 exposure deficits, but, particularly with
      exercise, improvement was evident early after exposure with or without O2. FEF25
      75 and FEV1 remained depressed on Day+3 after wetO2 and wetO2X.

PMID- 30192775
TI  - Transgressive segregations for agronomic improvement using interspecific crosses
      between C. arietinum L. x C. reticulatum Ladiz. and C. arietinum L. x C.
      echinospermum Davis species.
AB  - The wild species of chickpea have tremendous potential for enhancing genetic
      gains of cultigen and have resistant accessions against major biotic and abiotic
      stresses. In the present study, two wild annual accessions, one each of C.
      reticulatum Ladiz. (ILWC 229) and C. echinospermum Davis (ILWC 246) were assessed
      for their agro-morphological features and hybridized with different cultivated
      varieties (BGD 72, PBG 5, ICKG 96029, Pusa 372 and JG 11) of chickpea. Fertile F1
      plants were developed as revealed by their normal meiotic chromosomal
      configuration including high pollen stainability percentage and seed set. The
      effect of genetic and non-genetic factors on crossability performance with
      respect to pod and seed set was also evident under two growing conditions of
      North-Western Indian Himalayas. The segregation analysis using F2 phenotypic
      ratio of some distinct morphological (plant growth habit, stem pigmentation at
      seedling stage and testa texture) characters indicated their monogenic
      inheritance pattern. The study would also be useful to chickpea breeders to
      identify true to type interspecific plants. Further, the F1, F2 and F3
      generations of all seven crosses along with parents were evaluated under natural
      field condition to determine the extent of variability created into the
      cultivated background of chickpea. There was a wide range of variation in F3
      population against cold stress, suggesting selection of tolerant recombinant
      lines at an early stage. We also studied fruitful heterosis (%) as a useful
      approach, instead of residual heterosis to identify better performing
      transgressive segregants. The values of most of the interspecific crosses for
      important traits assessed in F2 and F3 generations were higher than that of
      better parent, suggesting isolation of inbred vigour for pod numbers and
      earliness. The results indicated that wild Cicer annual accessions of C.
      reticulatum and C. echinospermum species can be exploited after proper screening
      for traits of interest for diversification of cultivated gene pool and subsequent
      use in chickpea improvement.

PMID- 30192776
TI  - When to reveal what you feel: How emotions towards antagonistic out-group and
      third party audiences are expressed strategically.
AB  - In intergroup conflicts, expressed emotions influence how others see and react to
      those who express them. Here, we investigated whether this in turn implies that
      emotions may be expressed strategically. We tested whether emotion expression can
      differ from emotion experience, and whether emotion expression (more than emotion
      experience) is used to pursue specific goals. Specifically, we focused on whether
      support-seeking emotions (fear and sadness) are used to call for support from a
      powerful third party and contempt to distance from an antagonistic out-group. In
      two studies, using the same ostensible conflict, we manipulated whether
      participants communicated their emotions towards the out-group (no vs. yes) and
      third party (no vs. yes) and employed a between-subjects design in Study 1 (N =
      86) and a within-subjects design in Study 2 (N = 83). In both studies, we found
      that members of a disadvantaged group expressed reduced support-seeking emotions
      towards the out-group than they experienced (i.e., in conditions without an
      audience), providing support for the assumption that emotion expression does not
      necessarily reflect experience. Further, in Study 2, we found in line with
      expectations that the goal to call for support was more important in the
      communication with the third party than with the antagonistic out-group. The goal
      was best predicted by expressed support-seeking emotions, providing support for
      the assumption that emotion expression is used to pursue goals. Interestingly, we
      only found this association for a beneficial goal (i.e., calling for support) and
      not for distancing, a destructive goal. These results support the proposed
      strategic use of emotion expression and as such advance our understanding of the
      function of expressed emotions.

PMID- 30192777
TI  - Associations between health systems capacity and mother-to-child HIV prevention
      program outcomes in Zambia.
AB  - INTRODUCTION: Zambia has made substantial investments in health systems capacity,
      yet it remains unclear whether improved service quality improves outcomes. We
      investigated the association between health system capacity and use of prevention
      of mother-to-child HIV transmission (PMTCT) services in Zambia. MATERIALS AND
      METHODS: We analyzed data from two studies conducted in rural and semi-urban
      Lusaka Province in 2014-2015. Health system capacity, our primary exposure, was
      measured with a validated balanced scorecard approach. Based on WHO building
      blocks for health systems strengthening, we derived overall and domain-specific
      facility scores (range: 0-100), with higher scores indicating greater capacity.
      Our outcome, community-level maternal antiretroviral drug use at 12 months
      postpartum, was measured via self-report in a large cohort study evaluating PMTCT
      program impact. Associations between health systems capacity and our outcome were
      analyzed via linear regression. RESULTS: Among 29 facilities, median overall
      facility score was 72 (IQR:67-74). Median domain scores were: patient
      satisfaction 75 (IQR 71-78); human resources 85 (IQR:63-87); finance 50 (IQR:50
      67); governance 82 (IQR:74-91); service capacity 77 (IQR:68-79); service
      provision 60 (IQR:52-76). Our programmatic outcome was measured from 804 HIV
      infected mothers. Median community-level antiretroviral use at 12 months was 81%
      (IQR:69-89%). Patient satisfaction was the only domain score significantly
      associated with 12-month maternal antiretroviral use (beta:0.22; p = 0.02). When
      we excluded the human resources and finance domains, we found a positive
      association between composite 4-domain facility score and 12-month maternal
      antiretroviral use in peri-urban but not rural facilities. CONCLUSIONS: In these
      Zambian health facilities, patient satisfaction was positively associated with
      maternal antiretroviral 12 months postpartum. The association between overall
      health system capacity and maternal antiretroviral drug use was stronger in peri
      urban versus rural facilities. Additional work is needed to guide strategic
      investments for improved outcomes in HIV and broader maternal-child health region
      wide.

PMID- 30192778
TI  - Combined aerobic and resistance exercise training attenuates cardiac dysfunctions
      in a model of diabetes and menopause.
AB  - The study aimed at evaluating the effects of combined aerobic and resistance
      exercise training on cardiac morphometry and function, oxidative stress and
      inflammatory parameters in diabetic ovariectomized rats. For this, female Wistar
      rats (10 weeks-old) were divided into 4 groups (n = 8): euglycemic (E), diabetic
      (streptozotocin, 50 mg/kg, iv) (D), diabetic ovariectomized (DO) and trained
      diabetic ovariectomized (TDO). The combined exercise training was performed on a
      treadmill and in a ladder adapted to rats (8 weeks, at 40-60% of maximal
      capacity). The left ventricle (LV) morphometry and function were evaluated by
      echocardiography. Oxidative stress and inflammatory markers were measured on
      ventricles tissue. The sedentary diabetic animals (D and DO) showed impaired
      systolic and diastolic functions, as well as increased cardiac overload,
      evaluated by myocardial performance index (MPI- D: 0.32 +/- 0.05; DO: 0.39 +/-
      0.13 vs. E: 0.25 +/- 0.07), in relation to E group. Systolic and MPI dysfunctions
      were exacerbated in DO when compared to D group. The DO group presented higher
      protein oxidation and TNF-alpha/IL-10 ratio than D groups. Glutathione redox
      ratio (GSH/GSSG) and IL-10 were decreased in both D and DO groups when compared
      to E group. Exercise training improved exercise capacity, systolic and diastolic
      functions and MPI (0.18+/-0.11). The TDO group showed reduced protein oxidation
      and TNF-alpha/IL-10 ratio and increased GSH/GSSG and IL-10 in relation to the DO
      group. These results showed that combined exercise training was able to attenuate
      the cardiac dysfunctions, probably by reducing inflammation and oxidative stress
      in an experimental model of diabetes and menopause.

PMID- 30192779
TI  - Detection and characterization of Lactobacillus spp. in the porcine seminal
      plasma and their influence on boar semen quality.
AB  - The presence of pathogenic bacteria in ejaculates has been a topic in boar semen
      preservation over the last decades. Since little information is available on
      commensal bacteria in boar semen, the aim of the present study was to identify
      commensal lactobacilli in fresh cryopreserved boar semen and to examine their
      influence on boar semen quality. Therefore, 111 boar ejaculates were investigated
      for the presence of Lactobacillus species. Thirty samples (27%) contained viable
      Lactobacillus species (e.g. L. amylovorus, L. animalis, L. reuteri and Weisella
      minor). L. animalis and L. buchneri DSM 32407 (isolated from the bovine uterus)
      qualified for further examinations based on their growth rate in six antibiotic
      free boar semen extenders. After a 120 min short-term incubation with an
      antibiotic-free BTS-extender, progressive motility was diminished (P = 0.001)
      upon addition of 105 and 106 colony forming units (CFU/mL) L. animalis. The
      supplementation with L. buchneri DSM 32407 had no significant (P > 0.05)
      influence on sperm quality during short-term co-incubation. After 168 h long-term
      co-incubation, motility analysis revealed a negative (P = 0.026) impact of 105
      CFU/mL L. buchneri DSM 32407. A concentration- and storage-dependent effect is
      particularly obvious (P < 0.001) using 106 CFU/mL L. buchneri DSM 32407. Most
      notably, the thermo-resistance (TRT) for 106 CFU/mL L. buchneri DSM 32407 (P =
      0.001) was inferior to BTS with and without gentamicin after 72 and 168 h of
      semen co-incubation. The supplementation of 105 CFU/mL L. buchneri DSM 32407
      impaired progressive motility to a lesser extent. The percentage of
      mitochondrially active spermatozoa after 96 h (P = 0.009) and membrane-intact
      spermatozoa after 168 h (P < 0.001) was lower when 106 CFU/mL L. buchneri DSM
      32407 were suspended compared with all other groups. Finally, the addition of L.
      buchneri DSM 32407 to BTS-extended boar semen had no competitive effect on the
      total amount of bacteria 48 h after co-incubation. In summary, the present study
      demonstrated that there are Lactobacillus species present in the porcine seminal
      plasma, which can be cultivated using standard procedures. However, long-term co
      incubation of lactic acid bacteria with spermatozoa had a negative influence on
      spermatozoa.

PMID- 30192781
TI  - Health care costs of influenza-related episodes in high income countries: A
      systematic review.
AB  - INTRODUCTION: This study systematically reviews costing studies of seasonal
      influenza-like illness (ILI) in high-income countries. Existing reviews on the
      economic impact of ILI do not report information on drug consumption and its
      costs, nor do they provide data on the overall cost per episode. METHODS: The
      PRISMA-P checklist was used to design the research protocol. Studies included
      were cost of illness analysis (COI) and modeling studies that estimated the cost
      of ILI episodes. Records were searched from January 2000 to December 2016 in
      electronic bibliographic databases including Medline, Embase, Science Direct, the
      Cochrane Library, the Centre for Reviews and Disseminations of the University of
      York, and Google scholar. References from the included studies were hand-searched
      for completion. Abstract screening, full-text analysis and data extraction were
      performed by two reviewers independently and discrepancies were resolved by
      discussion with a third reviewer. A standardized, pre-piloted form was used for
      data extraction. All costs were converted to 2015 US$ Purchasing Power Parities.
      RESULTS: The literature search identified 5,104 records. After abstract and title
      screening, 76 studies were analyzed full-text and 27 studies were finally
      included in the review. Full estimates of the cost per episode range from US$19
      in Korea to US$323 in Germany. Particularly, the cost per episode of laboratory
      confirmed influenza cases was estimated between US$64 and US$73. Inpatient and
      outpatient services account for the majority of the costs. Differences in the
      estimates may reflect country-specific characteristics, as well as other study
      specific features including study design, identification strategy of ILI cases,
      study populations and types of costs included in the analysis. Children usually
      register higher costs, whereas evidence for the elderly is less conclusive.
      Patients risk-profile, co-morbidities and complications are the other important
      cost-drivers. None of the papers considered appropriateness in resource use (e.g.
      abuse of antibiotics). Despite cost of illness studies have ultimately a
      descriptive role, evidence on (in)appropriateness is useful for policy-makers.

PMID- 30192780
TI  - Increases in plasma corin levels following experimental myocardial infarction
      reflect the severity of ischemic injury.
AB  - Following acute myocardial infarction, clinical studies show alterations in the
      blood levels of corin, a cardiac-selective activator of the natriuretic peptides
      pro-atrial natriuretic peptide (pro-ANP) and pro-B-type natriuretic peptide (pro
      BNP). However, the temporal changes in circulating and cardiac corin levels and
      their relationships to the severity of myocardial infarction have not been
      studied. The main objective of this study was to examine the relationship between
      cardiac and circulating corin levels and their association with cardiac systolic
      function and infarct size during the early phase of acute myocardial infarction
      (<72 h) in a translationally relevant induced coronary ligation mouse model. This
      acute phase timeline was chosen to correlate with the clinical practice within
      which blood samples are collected from myocardial infarction patients. Heart and
      plasma samples were examined at 3, 24, and 72 hours post acute myocardial
      infarction. Plasma corin levels were examined by enzyme-linked immunosorbent
      assay, transcripts of cardiac corin, pro-ANP and pro-BNP by quantitative real
      time polymerase chain reaction, cardiac corin expression by immunohistology,
      infarct size by histology and heart function by echocardiography. Plasma corin
      levels were significantly increased at 3 (P<0.05), 24 (P<0.001), and 72 hours
      (P<0.01) post-acute myocardial infarction. In contrast, cardiac corin transcript
      levels dropped by 5% (P>0.05), 69% (P<0.001) and 65% (P<0.001) and immunoreactive
      cardiac corin protein levels dropped by 30% (P<0.05), 76% (P<0.001) and 75%
      (P<0.001), while cardiac pro-ANP and pro-BNP transcript levels showed an opposite
      pattern. Plasma corin levels were negatively correlated with immunoreactive
      cardiac corin (P<0.01), ejection fraction (P<0.05) and fractional shortening
      (P<0.05), but positively correlated with infarct size (P<0.01). In conclusion,
      acute myocardial infarction induces rapid increases in plasma corin and decreases
      in cardiac corin levels. In the early phase of acute myocardial infarction,
      plasma corin levels are inversely correlated with heart function and may reflect
      the severity of myocardial damage.

PMID- 30192782
TI  - Utility and variability of three non-invasive liver fibrosis imaging modalities
      to evaluate efficacy of GR-MD-02 in subjects with NASH and bridging fibrosis
      during a phase-2 randomized clinical trial.
AB  - BACKGROUND: Given the worldwide prevalence of NAFLD and NASH, there is a need to
      develop treatments to slow or reverse disease progression. GR-MD-02
      (galactoarabino-rhamnogalaturonate) has been shown to reduce hepatic fibrosis in
      animal studies, and lower serum biomarkers of NASH fibrogenesis in humans. The
      primary aim of this study was to determine the difference between four-months of
      treatment with GR-MD-02 or placebo in liver inflammation and fibrosis as measured
      by iron-corrected T1 (cT1) mapping, a non-invasive magnetic resonance imaging
      (MRI) biomarker that correlates with the extent of hepatic fibro-inflammatory
      disease. The secondary aims were to determine change in liver stiffness as
      measured by magnetic resonance elastography (MRE) and shear-wave ultrasonic
      elastography (LSM), and to explore test-retest repeatability of the three
      biomarkers. MATERIALS AND METHODS: Thirty subjects (13 females, 46-71 years) with
      NASH and advanced fibrosis were recruited. Subjects were randomized to receive 8
      mg.kg-1 GR-MD-02 (via IV infusion) or placebo, administered biweekly over a 16
      week period. Therapeutic efficacy was examined using cT1, MRE, and LSM.
      Statistical analyses on group differences in the biomarkers were performed using
      robust ANCOVA models adjusting for baseline measurement and additional
      covariates. RESULTS: There was no significant difference in cT1 (p = 0.16)
      between GR-MD-02 and placebo groups following a 16-week intervention. There was
      also no significant difference in liver stiffness, measured by MRE (p = 0.80) or
      LSM (p = 0.63), between groups. Examination of repeatability of the cT1, MRE and
      LSM revealed coefficient of variations of 3.1%, 11% and 40% respectively.
      CONCLUSIONS: 8 mg.kg-1 of GR-MD-02 had no significant effect on non-invasive
      biomarkers of liver inflammation or fibrosis over a 4-month period. Histological
      confirmation was not available in this study. The high reproducibility of the
      primary outcome measure suggests that cT1 could be utilized for monitoring
      longitudinal change in patients with NASH.

PMID- 30192784
TI  - The effect of dietary level of two inulin types differing in chain length on
      biogenic amine concentration, oxidant-antioxidant balance and DNA repair in the
      colon of piglets.
AB  - The effect of dietary level of two types of inulin on amine concentration, redox
      status and DNA glycosylase activity in the colon of piglets was investigated.
      Seven groups of piglets were fed diets without inulin addition (control) or with
      1%, 2% or 3% inulin with an average degree of polymerisation of 10 (IN10) or 23
      (IN23) for 40 days. The 2% and 3% IN10 diets increased tryptamine concentration
      in the proximal colon, while methylamine concentration in the distal colon was
      increased by the 1% and 3% IN10 diets. The 1% and 2% IN23 diets increased
      phenylethylamine and methylamine concentration in the proximal colon,
      respectively, while 1,7-diaminoheptane content was increased by both diets. Its
      concentration in the middle and distal colon was increased by the 1% and 2% IN23
      diet, respectively. There was no improvement in the oxidant-antioxidant balance
      in colonic digesta of piglets fed IN10 and IN23 diets. Piglets fed IN10 diets had
      lower 1,N6-etheno-2'-deoxyadenosine excision activity in each colon segment, as
      compared with the control group. It was also reduced by the 2% and 3% IN23 diets
      in the proximal colon, while in the middle and distal colon by all IN23 diets.
      Feeding all IN10 and IN23 diets reduced 3,N4-etheno-2'-deoxycytidine and 8-oxo
      deoxyguanosine excision activities in each colon segment. Feeding IN10 and IN23
      diets neither decreased amine concentrations nor improved the oxidant-antioxidant
      balance in colonic digesta of piglets. However, both types of inulin efficiently
      reduced the activity of DNA repair enzymes.

PMID- 30192783
TI  - Towards improved health service quality in Tanzania: An approach to increase
      efficiency and effectiveness of routine supportive supervision.
AB  - Effective supportive supervision of healthcare services is crucial for improving
      and maintaining quality of care. However, this process can be challenging in an
      environment with chronic shortage of qualified human resources, overburdened
      healthcare providers, multiple roles of district managers, weak supply chains,
      high donor fragmentation and inefficient allocation of limited financial
      resources. Operating in this environment, we systematically evaluated an approach
      developed in Tanzania to strengthen the implementation of routine supportive
      supervision of primary healthcare providers. The approach included a systematic
      quality assessment at health facilities using an electronic tool and subsequent
      result dissemination at council level. Mixed methods were used to compare the new
      supportive supervision approach with routine supportive supervision. Qualitative
      data was collected through in-depth interviews in three councils. Observational
      data and informal communication as well as secondary data complemented the data
      set. Additionally, an economic costing analysis was carried out in the same
      councils. Compared to routine supportive supervision, the new approach increased
      healthcare providers' knowledge and skills, as well as quality of data collected
      and acceptance of supportive supervision amongst stakeholders involved. It also
      ensured better availability of evidence for follow-up actions, including
      budgeting and planning, and higher stakeholder motivation and ownership of
      subsequent quality improvement measures. The new approach reduced time and cost
      spent during supportive supervision. This increased feasibility of supportive
      supervision and hence the likelihood of its implementation. Thus, the results
      presented together with previous findings suggested that if used as the standard
      approach for routine supportive supervision the new approach offers a suitable
      option to make supportive supervision more efficient and effective and therewith
      more sustainable. Moreover, the new approach also provides informed guidance to
      overcome several problems of supportive supervision and healthcare quality
      assessments in low- and middle income countries.

PMID- 30192785
TI  - Joint approach of diffusion- and perfusion-weighted MRI in intra-axial mass like
      lesions in clinical practice simulation.
AB  - Although advanced magnetic resonance imaging (MRI) techniques provide useful
      information for the differential diagnosis of intra-axial mass-like lesions, the
      specific diagnostic role of multimodal MRI over conventional magnetic resonance
      imaging (CMRI) alone in the differential diagnosis of mass-like lesions from a
      large heterogeneous cohort has not been studied. In this study, we aimed to
      determine the added value of a joint approach of diffusion-weighted imaging (DWI)
      and dynamic-susceptibility-contrast perfusion imaging (DSC-PWI) for diagnosis of
      intra-axial mass-like lesions, comparing them with CMRI alone. Furthermore, we
      performed these evaluations in a manner simulating clinical practice. Our
      institutional review board approved this retrospective study and waived the
      requirement for informed consent. A total of 1038 patients with intra-axial mass
      like lesions were retrospectively recruited according to their histological and
      clinico-radiological diagnoses made between January 2005 and December 2014. All
      patients underwent CMRI, DWI and DSC-PWI. The diagnostic accuracy and confidence
      in diagnosing each type of intra-axial mass-like lesions, and for differentiating
      the intra-axial brain tumors from non-neoplastic lesions, were compared according
      to the MRI protocols. The disease-specific sensitivity of joint approach differed
      according to specific disease entities in diagnosing each disease category. Joint
      approach provided the best diagnostic accuracy for discriminating intra-axial
      brain tumors from non-neoplastic lesions, with high diagnostic accuracy (95.3
      96.7%), specificity (82-84.0%), positive-predictive-value (97.0-97.3%), and
      negative-predictive-value (84.8-92.7%), with the reader's confidence values being
      significantly improved over those on CMRI alone (all p-values < 0.001). In
      conclusion, joint approach of DWI, DSC-PWI to CMRI helps to differentiate non
      neoplastic lesions from intra-axial brain tumors, and improves diagnostic
      confidence compared with CMRI alone. The benefit from the combined imaging
      differs for each disease category; thus joint approach needs to be customized
      according to clinical suspicion.

PMID- 30192786
TI  - Classes of depression symptom trajectories in patients with major depression
      receiving a collaborative care intervention.
AB  - PURPOSE: Collaborative care is effective in improving symptoms of patients with
      depression. The aims of this study were to characterize symptom trajectories in
      patients with major depression during one year of collaborative care and to
      explore associations between baseline characteristics and symptom trajectories.
      METHODS: We conducted a cluster-randomized controlled trial in primary care. The
      collaborative care intervention comprised case management and behavioral
      activation. We used the Patient Health Questionnaire-9 (PHQ-9) to assess symptom
      severity as the primary outcome. Statistical analyses comprised latent growth
      mixture modeling and a hierarchical binary logistic regression model. RESULTS: We
      included 74 practices and 626 patients (310 intervention and 316 control
      recipients) at baseline. Based on a minimum of 12 measurement points for each
      intervention recipient, we identified two latent trajectories, which we labeled
      'fast improvers' (60.5%) and 'slow improvers' (39.5%). At all measurements after
      baseline, 'fast improvers' presented higher PHQ mean values than 'slow
      improvers'. At baseline, 'fast improvers' presented fewer physical conditions,
      higher health-related quality of life, and had made fewer suicide attempts in
      their history. CONCLUSIONS: A notable proportion of 39.5% of patients improved
      only 'slowly' and probably needed more intense treatment. The third follow-up in
      month two could well be a sensible time to adjust treatment to support 'slow
      improvers'.

PMID- 30192787
TI  - Computing threshold antibody levels of protection in vaccine clinical trials: An
      assessment of methodological bias.
AB  - In the development of new vaccines, understanding the level of vaccine-induced
      antibody that is sufficient to protect against disease can simplify and expedite
      the development and licensing process. If there is an accepted threshold antibody
      level that is indicative of protection, then smaller trials measuring antibody
      concentration alone can be conducted to test new vaccines, instead of large
      efficacy studies powered on clinical outcomes. Commonly, threshold levels of
      protective antibody are determined from clinical efficacy trials in which
      clinical endpoints are measured on everyone and a small subset of participants
      have antibody concentrations measured. The proportion of participants with
      antibody below a threshold in each group in the immunogenicity subset can be
      compared to the proportions with disease in each group in the larger trial to
      find an appropriate threshold. Mathematically, this method seeks to compute an
      absolute threshold whereby antibody above the threshold provides complete,
      sterilizing immunity. However, in practice it is often understood that such
      thresholds may only be indicative of a relative degree of protection rather than
      an absolute one. Although this approach is common, the accuracy of such methods
      when the underlying mathematical assumptions do not hold true, has never been
      tested. We simulated data from clinical trial scenarios under varying assumptions
      of vaccine efficacy and calculated antibody thresholds of protection. We
      estimated the bias in the calculated thresholds derived from each scenario and
      showed that in many situations this method produces inflated estimates of
      thresholds, particularly if a vaccine induces high levels of antibody or when the
      underlying assumption of sterilizing immunity is violated.

PMID- 30192788
TI  - Next generation sequencing reveals a novel nonsense mutation in MSX1 gene related
      to oligodontia.
AB  - Tooth agenesis is one of the most common craniofacial disorders in humans. More
      than 350 genes have been associated with teeth development. In this study, we
      enrolled 60 child patients (age 13 to 17) with various types of tooth agenesis.
      Whole gene sequences of PAX9, MSX1, AXIN2, EDA, EDAR and WNT10a genes were
      sequenced by next generation sequencing on the Illumina MiSeq platform. We found
      previously undescribed heterozygous nonsense mutation g.8177G>T (c.610G>T) in
      MSX1 gene in one child. Mutation was verified by Sanger sequencing. Sequencing
      analysis was performed in other family members of the affected child. All family
      members carrying g.8177G>T mutation suffered from oligodontia (missing more than
      6 teeth excluding third molars). Mutation g.8177G>T leads to a stop codon
      (p.E204X) and premature termination of Msx1 protein translation. Based on
      previous in vitro experiments on mutation disrupting function of Msx1
      homeodomain, we assume that the heterozygous g.8177G>T nonsense mutation affects
      the amount and function of Msx1 protein and leads to tooth agenesis.

PMID- 30192790
TI  - Spatial models with covariates improve estimates of peat depth in blanket
      peatlands.
AB  - Peatlands are spatially heterogeneous ecosystems that develop due to a complex
      set of autogenic physical and biogeochemical processes and allogenic factors such
      as the climate and topography. They are significant stocks of global soil carbon,
      and therefore predicting the depth of peatlands is an important part of
      establishing an accurate assessment of their magnitude. Yet there have been few
      attempts to account for both internal and external processes when predicting the
      depth of peatlands. Using blanket peatlands in Great Britain as a case study, we
      compare a linear and geostatistical (spatial) model and several sets of
      covariates applicable for peatlands around the world that have developed over
      hilly or undulating terrain. We hypothesized that the spatial model would act as
      a proxy for the autogenic processes in peatlands that can mediate the
      accumulation of peat on plateaus or shallow slopes. Our findings show that the
      spatial model performs better than the linear model in all cases-root mean square
      errors (RMSE) are lower, and 95% prediction intervals are narrower. In support of
      our hypothesis, the spatial model also better predicts the deeper areas of peat,
      and we show that its predictive performance in areas of deep peat is dependent on
      depth observations being spatially autocorrelated. Where they are not, the
      spatial model performs only slightly better than the linear model. As a result,
      we recommend that practitioners carrying out depth surveys fully account for the
      variation of topographic features in prediction locations, and that sampling
      approach adopted enables observations to be spatially autocorrelated.

PMID- 30192789
TI  - Cellular immune response to human influenza viruses differs between H1N1 and H3N2
      subtypes in the ferret lung.
AB  - Seasonal influenza virus infections cause yearly epidemics which are the source
      of a significant public health burden worldwide. The ferret model for human
      influenza A virus (IAV) is widely used and has several advantages over other
      animal models such as comparable symptomology, similar receptor distribution in
      the respiratory tract to humans and the ability to be infected with human
      isolates without the need for adaptation. However, a major disadvantage of the
      model has been a paucity of reagents for the evaluation of the cellular immune
      response. Investigation of T-cell mediated immunity in ferrets is crucial to
      vaccine development and efficacy studies. In this study we have used commercially
      produced antibodies to ferret interferon gamma (IFN-gamma) allowing us to
      reliably measure influenza-specific IFN-gamma as a marker of the cellular immune
      response using both enzyme-linked immunospot (ELISpot) and enzyme-linked
      immunosorbent (ELISA) techniques. Here we demonstrate the application of these
      tools to evaluate cellular immunity in ferrets infected with clinically relevant
      seasonal H1N1 and H3N2 IAV subtypes at equivalent doses. Using small heparinised
      blood samples we were able to observe the longitudinal influenza-specific IFN
      gamma responses of ferrets infected with both seasonal subtypes of IAV and found
      a notable increase in influenza-specific IFN-gamma responses in circulating
      peripheral blood within 8 days post-infection. Both seasonal strains caused a
      well-defined pattern of influenza-specific IFN-gamma responses in infected
      ferrets when compared to naive animals. Additionally, we found that while the
      influenza specific IFN-gamma responses found in peripheral circulating blood were
      comparable between subtypes, the influenza specific IFN-gamma responses found in
      lung lymphocytes significantly differed. Our results suggest that there is a
      distinct difference between the ability of the two seasonal influenza strains to
      establish an infection in the lung of ferrets associated with distinct signatures
      of acquired immunity.

PMID- 30192791
TI  - HIV testing and pre-exposure prophylaxis (PrEP) use, familiarity, and attitudes
      among gay and bisexual men in the United States: A national probability sample of
      three birth cohorts.
AB  - This study examined HIV testing and use, familiarity, and attitudes toward pre
      exposure prophylaxis (PrEP) among HIV-negative gay and bisexual men in the United
      States. A national probability sample (N = 470) of three age cohorts (18-25, 34
      41, and 52-59 years) completed a survey between March, 2016 and March, 2017. Most
      men did not meet CDC recommendations for HIV testing, and 25.2% of men in the
      younger cohort had never tested. Only 4.1% used PrEP across cohorts. Visiting an
      LGBT clinic and searching for LGBT resources online were associated with PrEP
      use. Men in the middle cohort were more familiar with PrEP (79%) than men in the
      younger (52%) and older (57%) cohorts. Bisexual and non-urban men were less
      familiar with PrEP. Attitudes were positive among most men (68.4%) familiar with
      PrEP. Findings suggest that most men potentially at risk for HIV do not meet CDC
      guidelines for testing, and PrEP use continues to be minimal. Efforts to educate
      gay and bisexual men about HIV risk and prevention need to be reinvigorated and
      expanded to include non-gay-identified and non-urban men.

PMID- 30192792
TI  - Preparation, characterisation, and controlled release of sex pheromone-loaded
      MPEG-PCL diblock copolymer micelles for Spodoptera litura (Lepidoptera:
      Noctuidae).
AB  - Sex pheromones are important for agricultural pest control. The main sex
      pheromone components of Spodoptera litura are (Z,E)-9,11- and (Z,E)-9,12
      tetradecadienyl acetate (Z9,E11-14:Ac; Z9,E12-14:Ac). In this study, we
      investigated the optimal conditions for encapsulation of S. litura sex
      pheromonesin micelles via the self-assembly method using monomethoxy poly
      (ethylene glycol)-poly (epsilon-caprolactone) (MPEG-PCL) as a biodegradable wall
      forming material with low toxicity. In the L9(34) orthogonal experiment, 3
      amphiphilic block copolymers, with different hydrophilicity to hydrophobicity
      ratios, were examined. Optimal encapsulation conditions included stirring of
      MPEG5000-PCL2000 at 1000 rpm at 30 degrees C with 2.5:1 wall-forming: core
      material mass ratio. S. litura sex pheromone-loaded MPEG5000-PCL2000 micelles
      presented a homogeneous spherical morphology with apparent core-shell structure.
      The release kinetics of optimized MPEG5000-PCL2000 micelles was best explained by
      a first-order model. Encapsulated Z9,E11-14:Ac and Z9,E12-14:Ac were released
      slowly, not suddenly. Methyl oleate (MO) was used as an agent to control micellar
      release performance. When MO content equalled block content, micelle half-life
      could be prolonged, thereby controlling the release speed. Overall, our results
      showed MPEG-PCL as a promising controlled-release substrate for sex pheromones.

PMID- 30192793
TI  - Evaluation of delivered dose to a moving target by 4D dose reconstruction in
      gated volumetric modulated arc therapy.
AB  - PURPOSE: To develop a 4D dose reconstruction method and to evaluate the delivered
      dose in respiratory-gated volumetric modulated arc therapy (VMAT). MATERIALS AND
      METHODS: A total 112 treatment sessions of gated VMAT for 30 stereotactic body
      radiotherapy (SBRT) patients (10 lung, 10 liver, and 10 pancreas) were evaluated.
      For respiratory-gated SBRT, 4DCT was acquired, and the CT data at the end-exhale
      phase was used for a VMAT plan. The delivered dose was reconstructed using a
      patient's respiratory motion and machine motion acquired during the beam
      delivery. The machine motion was obtained from the treatment log file, while the
      target position was estimated from an external respiratory marker position. The
      target position was divided into 1-mm position bins, and sub-beams with beam
      isocenters corresponding to each position bin were created in a motion mimicking
      plan, reflecting motion data including MLC leaf positions and gantry angle and
      target position data during beam treatment. The reconstructed 4D dose was
      compared with the dose of the original plan using these dosimetric parameters;
      the maximum dose (Dmax) and mean dose (Dmean) of gross target volume (GTV) or
      organs at risk (spinal cord, esophagus, heart, duodenum, kidney, spinal cord, and
      stomach). The minimum dose (Dmin) to GTV was also calculated to verify cold spots
      in tumors. RESULTS: There was no significant difference of dose parameters regard
      to the GTV in all tumors. For the liver cases, there were significant differences
      in the Dmax of duodenum (-4.2 +/- 1.4%), stomach (-3.5 +/- 4.2%), left kidney (
      4.1 +/- 2.8%), and right kidney (-3.2 +/- 1.3%), and in the Dmean of duodenum (
      3.8 +/- 1.4%), stomach (-3.9 +/- 2.2%), left kidney (-3.1 +/- 2.8%), and right
      kidney (-4.1 +/- 2.6%). For the pancreas cases, there were significant
      differences in the Dmax of stomach (2.1 +/- 3.0%), and in the Dmean of liver (1.5
      +/- 0.6%), duodenum (-1.0 +/- 1.4%), stomach (2.1 +/- 1.6%), and right kidney (
      1.3 +/- 0.9%). The average gamma pass rates were 97.6 +/- 4.8% for lung cases,
      99.6 +/- 0.5% for liver cases, and 99.5 +/- 0.5% for pancreas cases. Most cases
      showed insignificant dose variation, with gamma pass rates higher than 98%,
      except for two lung cases with gamma pass rates of 86.9% and 90.6%. The low gamma
      pass rates showed larger global motion ranges resulting from the baseline shift
      during beam delivery. CONCLUSION: The actual delivered dose in thoracic and
      abdominal VMAT under breathing motion was verified by 4D dose reconstruction
      using typical treatment equipment and software. The proposed method provides a
      verification method for the actual delivered dose and could be a dosimetric
      verification QA tool for radiation treatment under various respiratory management
      techniques.

PMID- 30192794
TI  - Phylogeny of the spider mite sub-family Tetranychinae (Acari: Tetranychidae)
      inferred from RNA-Seq data.
AB  - Phylogenetic trees of spider mites were previously obtained using 18S and 28S
      rRNA genes. Because some of the bootstrap values were relatively low, these trees
      were unable to completely resolve the phylogeny. Here, we obtained RNA-Seq data
      for the 72 known species (73 strains) of spider mites to analyze the phylogeny of
      the sub-family Tetranychinae. The data were de novo assembled into a total
      alignment length of 790,047 bases corresponding to 264,133 amino acid residues in
      652 genes. The sequence dataset was 200 times larger than the data used in the
      previous study. The new trees were much more robust and more clearly defined the
      clades of the tribes and the genera of the sub-family Tetranychinae. The tribe
      Tetranychini was polyphyletic because a monophyletic clade of Eurytetranychini
      was placed inside it. The six genera from which two or more species were sampled
      appeared to be monophyletic, but four genera (Schizotetranychus, Eotetranychus,
      Oligonychus and Tetranychus) appeared to be polyphyletic. These results strongly
      support the previous molecular inference of the polyphyletic tribes and genera,
      although the molecular phylogeny of the sub-family Tetranychinae does not fully
      agree with the current morphology-based taxonomy. The taxonomy of the sub-family
      Tetranychinae should be revised according to the molecular relationships revealed
      by this study.

PMID- 30192795
TI  - Seroprevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) among human
      immunodeficiency virus (HIV)-infected patients in an HBV endemic area in Brazil.
AB  - BACKGROUND: Hepatitis B virus (HBV) and hepatitis C virus (HCV) are a common
      cause of complications in liver disease and immunological impairment among human
      immunodeficiency virus (HIV)-infected patients. The aim of this study was to
      assess the seroprevalence of HBV and HCV and their correlation with CD4+ T-cells
      among HIV-infected patients in an HBV endemic area. METHODS: A cross-sectional
      observational and retrospective study was carried out in a reference center in
      Southern Brazil between January 2005 and December 2016. Socio-demographic data
      were collected by using a structured questionnaire. Serological tests and
      analysis of CD4+ T-cell count levels were performed using standard procedures.
      RESULTS: The seroprevalence of HIV-HBV, HIV-HCV, and HIV-HBV-HCV coinfections was
      3.10%, 3.10%, and 0.16%, respectively. At baseline, anti-hepatitis B surface and
      anti-hepatitis B core antigens were detected in 46.27% and 16.74% of HIV
      monoinfected patients and in 31.25% and 21.86% of the HIV-HCV coinfected
      patients, respectively. The median CD4+ T-cell count at baseline in the HIV
      monoinfected group was higher than that in the HIV-coinfected groups, but without
      statistical significance. The median CD4+ T-cell count and the CD4/CD8 ratio were
      significantly higher in HIV-HBV and HIV-HCV groups after 24 months of combination
      antiretroviral therapy (cART) compared to the pre-cART values. When comparing
      patients with HIV-HBV and HIV-HCV on cART, CD4+ T-cell recovery was more rapid
      for HIV-HBV patients. CONCLUSION: Although the analyzed region was endemic for
      HBV, the prevalence of HIV-HBV and HIV-HCV coinfection was lower than the rate
      found in the general population of Brazil. HBV and HCV had no significant impact
      on CD4+ T-cell counts among HIV-infected patients at baseline.

PMID- 30192797
TI  - 900MHz 1H-/13C-NMR analysis of 2-hydroxyglutarate and other brain metabolites in
      human brain tumor tissue extracts.
AB  - PURPOSE: To perform in vitro high-resolution 900 MHz magnetic resonance
      spectroscopy (NMR) analysis of human brain tumor tissue extracts and analyze for
      the oncometabolite 2-hydroxyglutarate (2HG) and other brain metabolites, not only
      for 1H but also for 13C with indirect detection by heteronuclear single quantum
      correlation (HSQC). MATERIAL AND METHODS: Four surgically removed human brain
      tumor tissue samples were used for extraction and preparation of NMR samples.
      These tissue samples were extracted with 4% perchloric acid and chloroform,
      freeze-dried, then dissolved into 0.28 mL of deuterium oxide (D2O, 99.9 atom %
      deuterium) containing 0.025 wt % sodium 3-(trimethylsilyl)propionate-2,2,3,3-d4
      (TSP). All samples were adjusted to pH range of 6.9-7.1 before finally
      transferred to 5 mm ShigemiTM NMR microtube. NMR experiments were performed on
      Bruker DRX 900 MHz spectrometer with 1H/13C/15N Cryo-probeTM with Z-gradient,
      without further temperature control for the samples. All chemical shift values
      were presented relative to TSP at 0.00 ppm for both 1H and 13C. 1H 1D, 1H-13C
      HSQC, 1H-1H correlation spectroscopy (COSY) and 1H-13C heteronuclear multiple
      bond correlation (HMBC) spectra were acquired and analyzed. RESULTS: 2
      hydroxyglutarate, an oncometabolite associated with gliomas with IDH mutations,
      was successfully detected and assigned by both 1H-13C HSQC and 1H-1H COSY
      experiments as well as 1H 1D experiments in two of the tissue samples. In
      particular, to our knowledge this work shows the first example of detecting 900
      MHz 13C-NMR spectral lines of 2-hydroxyglutarate in human brain tumor tissue
      samples. In addition to the oncometabolite 2-hydroxyglutarate, at least 42 more
      metabolites were identified from our series of NMR experiment. CONCLUSION: The
      detection of 2-hydroxyglutarate and other metabolites can be facilitated by
      homonuclear and heteronuclear two-dimensional 900 MHz NMR spectroscopy even in
      case of real tumor tissue sample extracts without physical separation of
      metabolites.

PMID- 30192796
TI  - Comparative transcriptome meta-analysis of Arabidopsis thaliana under drought and
      cold stress.
AB  - Multiple environmental stresses adversely affect plant growth and development.
      Plants under multiple stress condition trigger cascade of signals and show
      response unique to specific stress as well as shared responses, common to
      individual stresses. Here, we aim to identify common and unique genetic
      components during stress response mechanisms liable for cross-talk between
      stresses. Although drought and cold stress have been widely studied,
      insignificant information is available about how their combination affects
      plants. To that end, we performed meta-analysis and co-expression network
      comparison of drought and cold stress response in Arabidopsis thaliana by
      analyzing 390 microarray samples belonging to 29 microarray studies. We observed
      6120 and 7079 DEGs (differentially expressed genes) under drought and cold stress
      respectively, using Rank Product methodology. Statistically, 28% (2890) DEGs were
      found to be common in both the stresses (i.e.; drought and cold stress) with most
      of them having similar expression pattern. Further, gene ontology-based
      enrichment analysis have identified shared biological processes and molecular
      mechanisms such as-'photosynthesis', 'respiratory burst', 'response to hormone',
      'signal transduction', 'metabolic process', 'response to water deprivation',
      which were affected under cold and drought stress. Forty three transcription
      factor families were found to be expressed under both the stress conditions.
      Primarily, WRKY, NAC, MYB, AP2/ERF and bZIP transcription factor family genes
      were highly enriched in all genes sets and were found to regulate 56% of common
      genes expressed in drought and cold stress. Gene co-expression network analysis
      by WGCNA (weighted gene co-expression network analysis) revealed 21 and 16 highly
      inter-correlated gene modules with specific expression profiles under drought and
      cold stress respectively. Detection and analysis of gene modules shared between
      two stresses revealed the presence of four consensus gene modules.

PMID- 30192798
TI  - Cancer-related effects on relationships, long-term psychological status and
      relationship satisfaction in couples whose child was treated for leukemia: A
      PETALE study.
AB  - OBJECTIVES: Follow-up studies suggest that the psychosocial impact of pediatric
      cancer on parents often extends beyond the end of their child's cancer
      treatments, and parents can continue to experience both individual and
      relationship effects. In a long-term study of parents of children who were
      treated for acute lymphoblastic leukemia (ALL), we aimed to: 1) describe parents'
      adjustment (psychological distress, relationship satisfaction; 2) describe the
      perceived impact of cancer on couples' relationship, and; 3) identify to what
      extent the perceived impact of cancer on the couple is related to both parents'
      long-term adjustment. METHODS: Parents of childhood ALL survivors (n = 103
      couples) were surveyed as part of a cohort recall (PETALE cohort). Both parents
      completed questionnaires exploring adjustment (Brief Symptom Inventory-18, Dyadic
      Adjustment Scale) and perceived impact of cancer on the relationship (Impact of
      Cancer on the Couple). Mothers' and fathers' scores were compared using MANOVAs.
      We also examined the degree to which a parent's perceived changes in relationship
      dynamics following their child's cancer were associated with their own current
      adjustment (actor effects), and their partner's current adjustment (partner
      effects) using the Actor-Partner Interdependence Model (APIM). RESULTS:
      Frequencies of current distress were normative in parents (mothers/fathers):
      general distress (6.8/7.8%), anxiety (5.8/6.8%), depression (2.9/6.8%),
      somatization (13.6/9.7%), and relationship distress (21.4/20.4%). Mothers and
      fathers typically agreed on their reported relationship satisfaction, and the
      perceived nature of relationship changes following the illness. Dyadic analyses
      indicated that whereas mothers' adjustment was related to their own perceived
      relationship changes, fathers' adjustment was primarily related to their
      partner's perceptions. CONCLUSION: In long-term stable couples, mothers may act
      as an influential bridge connecting the illness experiences of survivors and
      fathers. This could explain why mothers' perceptions of relationship changes were
      related to their partners' long-term adjustment, which was not the case for
      fathers.

PMID- 30192800
TI  - Evidence for magnitude representations of social hierarchies: Size and distance
      effects.
AB  - Social status is often metaphorically construed in terms of spatial relations
      such as height, size, and numerosity. This has led to the idea that social status
      might partially be represented by an analogue magnitude system, responsible for
      processing the magnitude of various physical and abstract dimensions.
      Accordingly, processing of social status should obey Weber's law. We conducted
      three studies to investigate whether social status comparisons would indicate
      behavioral outcomes derived from Weber's law: the distance effect and the size
      effect. Dependent variable was the latency of status comparisons for a variety of
      both learned and familiar hierarchies. As predicted and in line with previous
      findings, we observed a clear distance effect. However, the effect of size
      variation differed from the size effect hypothesized a priori, and an unexpected
      interaction between the two effects was observed. In conclusion, we provide a
      robust confirmation of previous observations of the distance effect in social
      status comparisons, but the shape of the size effect requires new theorizing.

PMID- 30192799
TI  - Quantitative lipidomic analysis of mouse lung during postnatal development by
      electrospray ionization tandem mass spectrometry.
AB  - Lipids play very important roles in lung biology, mainly reducing the alveolar
      surface tension at the air-liquid interface thereby preventing end-expiratory
      collapse of the alveoli. In the present study we performed an extensive
      quantitative lipidomic analysis of mouse lung to provide the i) total lipid
      quantity, ii) distribution pattern of the major lipid classes, iii) composition
      of individual lipid species and iv) glycerophospholipid distribution pattern
      according to carbon chain length (total number of carbon atoms) and degree of
      unsaturation (total number of double bonds). We analysed and quantified 160
      glycerophospholipid species, 24 sphingolipid species, 18 cholesteryl esters and
      cholesterol from lungs of a) newborn (P1), b) 15-day-old (P15) and c) 12-week-old
      adult mice (P84) to understand the changes occurring during postnatal pulmonary
      development. Our results revealed an increase in total lipid quantity,
      correlation of lipid class distribution in lung tissue and significant changes in
      the individual lipid species composition during postnatal lung development.
      Interestingly, we observed significant stage-specific alterations during this
      process. Especially, P1 lungs showed high content of monounsaturated lipid
      species; P15 lungs exhibited myristic and palmitic acid containing lipid species,
      whereas adult lungs were enriched with polyunsaturated lipid species. Taken
      together, our study provides an extensive quantitative lipidome of the postnatal
      mouse lung development, which may serve as a reference for a better understanding
      of lipid alterations and their functions in lung development and respiratory
      diseases associated with lipids.

PMID- 30192801
TI  - Nesting ecology of hawksbill turtles, Eretmochelys imbricata, in an extreme
      environmental setting.
AB  - Relatively few details of hawksbill turtle (Eretmochelys imbricata) nesting
      ecology exist within the Arabian Gulf. Moreover, little is known about how their
      nesting dynamics compare to nesting populations throughout the rest of the world.
      Due to the extreme environmental setting, nesting ecology of hawksbills in the
      Arabian Gulf is of significant interest to researchers and conservationists. The
      current research reports on a long-term tagging and monitoring program undertaken
      at Fuwairit beach, Qatar. To investigate nesting behavior, site surveys and
      tagging were employed from 2010 to 2016. Presence of nests and clutch sizes were
      confirmed by excavation. Over the entire study period, nesting hawksbills had a
      mean curved carapace length of 70.8 cm (SD+/-2.8). A total 187 nests were
      confirmed, which contained a mean 78.9 eggs per clutch (SD+/-17.1), over an
      annual nesting season that lasted an average of 52.2 days (SD+/-6.3) from the
      start of April to the start of June. Meta-analysis with other global regions
      showed these characteristics to be significantly reduced when compared to nesting
      hawksbills from other populations. Meteorological data analysis showed air
      temperatures in the Arabian Gulf to increase on average 13.2 degrees C (SD+/
      0.26) from start to the end of nesting annually, which is significantly greater
      than other global nesting regions. Their smaller body size and reduced fecundity
      coupled with the extreme change in ambient air temperatures support the
      hypothesis that hawksbills in the region are more at risk than the already
      critically endangered hawksbill populations elsewhere in the world.

PMID- 30192803
TI  - Assessment of community led total sanitation and hygiene approach on improvement
      of latrine utilization in Laelay Maichew District, North Ethiopia. A comparative
      cross-sectional study.
AB  - BACKGROUND: Lack of latrines remain a widespread health and environmental hazard
      in many developing countries. Low latrine utilization mostly affects the poor,
      rural and marginalized communities as the majority of those who do not use
      improved latrines live in rural areas where 90% of all open defecation takes
      place. The counterpart to this problem, Community-Led Total Sanitation, and
      hygiene (CLTSH) is an approach that involves facilitating a process to inspire
      and empower communities to stop open defecation and to build and use latrines in
      a participatory manner. OBJECTIVE: This study was aimed at assessing the
      Community Led Total Sanitation and Hygiene approach on improvement of latrine
      utilization in Laelay Maichew District of Central Zone, Northern Ethiopia.
      METHODS: A comparative cross-sectional study was conducted in Laelay Maichew
      District of Central Zone, Northern Ethiopia from November 2016 to January 2017.
      The study subjects were randomly selected 388 households from CLTSH implemented
      kebeles and 388 households from CLTSH non-implemented kebeles. Systematic random
      sampling technique was used to select households among proportionally allocated
      sample frame of households. Then, Interview of household heads using semi
      structured questionnaire was conducted to collect data. Finally, data were
      entered and analyzed using SPSS version 20.0. Bivariate Logistic regressions
      model was used to identify candidates of multiple logistic regressions. Those P
      values < 0.25 were considered as candidates to multiple logistic regressions to
      determine independent factors of latrine utilization. Variables with Odds Ratio
      at 95% CI and P-value < 0.05 was considered statistically significant. The study
      obtained approval from Aksum University Institutional Review Board before its
      commencement. RESULT: This study indicated that the level of latrine utilization
      and latrine availability in CLTSH implemented kebeles were greater than that of
      CLTSH Non-implemented kebeles. The finding of this study revealed that the rate
      of latrine utilization in the rural community of Laelay-matches district was
      about 47.4%, 95% CI (42.9%-51.8%). The majority (71.1%) of household in CLTSH
      implemented kebeles and (93.5%) of households in CLTSH non-implemented kebeles
      did not have hand washing facility near the latrine. Households which had no
      fresh excreta in around latrine were significantly 11.5 times higher than [AOR:
      11.5, 95% CI (0.18, 50.2)] utilizing their latrine in CLTSH implemented kebeles.
      CONCLUSION: The study showed that the level of latrine utilization in CLTSH
      implemented and that of CLTSH non-implemented kebeles was low. Therefore,
      concerted efforts should be made by local and national governmental and non
      governmental organization to should be used to promote behavioral change in the
      communities to implement community-led total sanitation and hygiene for improving
      latrine utilization.

PMID- 30192802
TI  - EGFR signaling suppresses type 1 cytokine-induced T-cell attracting chemokine
      secretion in head and neck cancer.
AB  - Resistance to antitumor immunity can be promoted by the oncogenic pathways
      operational in human cancers, including the epidermal growth factor receptor
      (EGFR) pathway. Here we studied if and how EGFR downstream signaling in head and
      neck squamous cell carcinoma (HNSCC) can affect the attraction of immune cells.
      HPV-negative and HPV-positive HNSCC cell lines were analyzed in vitro for CCL2,
      CCL5, CXCL9, CXCL10, IL-6 and IL-1beta expression and the attraction of T cells
      under different conditions, including cetuximab treatment and stimulation with
      IFNgamma and TNFalpha using qPCR, ELISA and migration experiments. Biochemical
      analyses with chemical inhibitors and siRNA transfection were used to pinpoint
      the underlying mechanisms. Stimulation of HNSCC cells with IFNgamma and TNFalpha
      triggered the production of T-cell attracting chemokines and required c-RAF
      activation. Blocking of the EGFR with cetuximab during this stimulation increased
      chemokine production in vitro, and augmented the attraction of T cells.
      Mechanistically, cetuximab decreased the phosphorylation of MEK1, ERK1/2, AKT,
      mTOR, JNK, p38 and ERK5. Chemical inhibition of EGFR signaling showed a
      consistent and pronounced chemokine production with MEK1/2 inhibitor PD98059 and
      JNK inhibitor SP600125, but not with inhibitors of p38, PI3K or mTOR. Combination
      treatment with cetuximab and a MEK1/2 or JNK inhibitor induced the highest
      chemokine expression. In conclusion, overexpression of EGFR results in the
      activation of multiple downstream signaling pathways that act simultaneously to
      suppress type 1 cytokine stimulated production of chemokines required to amplify
      the attraction of T cells.

PMID- 30192804
TI  - Automated decision support in melanocytic lesion management.
AB  - An automated melanocytic lesion image-analysis algorithm is described that aims
      to reproduce the decision-making of a dermatologist. The utility of the algorithm
      lies in its ability to identify lesions requiring excision from lesions not
      requiring excision. Using only wavelet coefficients as features, and testing
      three different machine learning algorithms, a cohort of 250 images of pigmented
      lesions is classified based on expert dermatologists' recommendations of either
      excision (165 images) or no excision (85 images). It is shown that the best
      algorithm utilises the Shannon4 wavelet coupled to the support vector machine,
      where the latter is used as the classifier. In this case the algorithm, utilising
      only 22 othogonal features, achieves a 10-fold cross validation sensitivity and
      specificity of 0.96 and 0.87, resulting in a diagnostic-odds ratio of 261. The
      advantages of this method over diagnostic algorithms-which make a melanoma/no
      melanoma decision-are twofold: first, by reproducing the decision-making of a
      dermatologist, the average number of lesions excised per melanoma among
      practioners in general can be reduced without compromising the detection of
      melanoma; and second, the intractable problem of clinically differentiating
      between many atypical dysplastic naevi and melanoma is avoided. Since many
      atypical naevi that require excision on clinical grounds will not be melanoma,
      the algorithm-in contrast to diagnostic algorithms-can aim for perfect
      specificities without clinical concerns, thus lowering the excision rate of non
      melanoma. Finally, the algorithm has been implemented as a smart phone
      application to investigate its utility in clinical practice and to streamline the
      assimilation of hitherto unseen tested images into the training set.

PMID- 30192805
TI  - Knowledge, stigma, health seeking behaviour and its determinants among patients
      with post kalaazar dermal leishmaniasis, Bihar, India.
AB  - BACKGROUND: Lesishmaniasis is a neglected tropical disease endemic in Bihar,
      India. Inappropriate health seeking behaviour of post kala-azar dermal
      leishmaniasis (PKDL) patients may increase the disease duration, severity and
      transmissibility. Simultaneously, lack of knowledge and perceived stigma may also
      increase the length of delay in receiving treatment. This ultimately effects the
      kala-azar elimination program. METHODS: A cross sectional study was conducted in
      120 confirmed PKDL patients, aged 18 years and older. Data related to knowledge
      and health seeking behaviour was collected by a pre-tested questionnaire. EMIC
      stigma scale was used for assessing the perceived stigma. Patients were
      personally interviewed after taking informed consent. Data analysis was done by
      using SPSS 16 software. RESULTS: The time between appearance of symptoms and
      first medical consultation (patient delay) ranged from 15 days to 5475 days (15
      years) with a median of 285 days. The time between first medical consultations to
      onset of specific treatment (system delay) ranged from 2 to 5475 days with a
      median of 365 days. Many patients approached first to quacks (8.4%), homeopathic
      and ayurvedic practitioners (25.8%) upon recognition of symptoms. Majority of the
      patients (68.3%) had poor knowledge about PKDL and its vector. Type of skin
      lesions and gender had significant association with patient delay and system
      delay respectively (p<0.05). Distance to primary health centre (PHC) had
      significant association with patients delay as well as system delay (p<0.05).
      Patients with younger age, unmarried and polymorphic lesions had higher stigma
      (p<0.05). Patients with PKDL feel stigmatized in different areas. CONCLUSION:
      PKDL treatment delays were unacceptably high and patients had poor knowledge
      compounded with feelings of stigmatization. To reduce the delay, a system may be
      evolved to establish some sort of public-private collaboration, besides awareness
      programs should be tailored, and implemented for improving the patient education
      regarding the disease and its linkage with VL.

PMID- 30192806
TI  - Hybridization between two bitterling fish species in their sympatric range and a
      river where one species is native and the other is introduced.
AB  - The distributions of two bitterling fish (subfamily: Acheilognathinae), Tanakia
      lanceolata and T. limbata, overlap in western Japan. Acheilognathinae fish lay
      their eggs in the gills of freshwater bivalves, and the early juvenile stage
      develops in the gills. Populations of freshwater bivalves are declining
      worldwide, which has limited the number of spawning substrate for bitterlings. T.
      limbata has been artificially introduced to some rivers in Ehime, Japan, where it
      coexists with native T. lanceolata, and some hybrids have been observed. We
      collected both species from several sites in western Japan, and from the Kunichi
      River system in Ehime, and analyzed genetic population structure based on six
      microsatellite loci and sequences of the mitochondrial cytochrome b gene.
      Structure analysis identified three genetically distinct populations: T.
      lanceolata, T. limbata "West Kyushu", and T. limbata "Setouchi". Two clades of T.
      limbata were also supported by molecular phylogenetic analyses based on
      cytochrome b. Hybrids in Ehime originated mostly from interbreeding between male
      T. lanceolata and female T. limbata "West Kyushu", and made up 10.2% of all
      collected fish, suggesting that hybrids occurred frequently between females of
      colonizing species and males of native species. On the other hand, interspecific
      hybrids were detected at rates of 40.0%, 20.0%, and 17.6% in the Ima River
      (Fukuoka), Midori River (Kumamoto), and Kase River (Saga), respectively, which
      are naturally sympatric regions. We found a few T. limbata "Setouchi" in the
      Midori and Kase Rivers, which were supposed to be introduced from other regions,
      coexisting with native T. limbata "West Kyushu", and this cryptic invasion may
      have triggered the interspecific hybridization. These results suggest that
      artificial introduction of a fish species, a decline in the unionid population,
      and degradation of habitat have caused broad hybridization of bitterlings in
      western Japan.

PMID- 30192807
TI  - Spirituality in pain medicine: A randomized experiment of pain perception, heart
      rate and religious spiritual well-being by using a single session meditation
      methodology.
AB  - : The aim of this study is to investigate different effects on pain perception
      among randomly assigned volunteers practicing meditation compared to a relaxation
      condition. The study examines whether participants of the experimental conditions
      (meditation versus relaxation) differ in the change of pain perception and heart
      rate measurement and in religious and spiritual well-being after an intervention.
      METHOD: 147 volunteers (long-term practitioners and novices) were randomly
      assigned to the experimental conditions with a headphone guided 20-minute single
      session intervention. The change in their pre- and post-intervention pain
      perception was measured using Quantitative Sensory Testing and Cold Pressor
      Testing (CPTest), their stress-level was compared by monitoring heart rate, and
      their religious and spiritual well-being by using the Multidimensional Inventory
      for Religious/Spiritual Well-Being (MI-RSB48). Additionally, dimensions of the
      Brief Symptom Inventory (BSI) measured the psychological resilience of the
      participants; pain and stress experience, and the state of relaxation and
      spirituality experience were assessed. Five persons were excluded due to failure
      in measuring the heart rate and 29 participants had to be excluded because of
      high values on the BSI. RESULTS: The meditation group showed an increase in their
      pain tolerance on the CPTest and a decrease in their pain intensity for heat
      after the experimental condition, in contrast to the relaxation group.
      Futhermore, the meditation group showed a higher level of religious spiritual
      well-being (MI-RSB48 Total score) as well as in the sub-dimensions General
      Religiosity, Forgiveness, and Connectedness after the experimental condition,
      compared to the relaxation group. Our data is consistent with the hypothesis that
      meditation increases pain tolerance and reduces pain intensity, however, further
      work is required to determine whether meditation contains similar implications
      for pain patients.

PMID- 30192808
TI  - Prediction model for pancreatic cancer risk in the general Japanese population.
AB  - Genome-wide association studies (GWASs) have identified many single nucleotide
      polymorphisms (SNPs) that are significantly associated with pancreatic cancer
      susceptibility. We sought to replicate the associations of 61 GWAS-identified
      SNPs at 42 loci with pancreatic cancer in Japanese and to develop a risk model
      for the identification of individuals at high risk for pancreatic cancer
      development in the general Japanese population. The model was based on data
      including directly determined or imputed SNP genotypes for 664 pancreatic cancer
      case and 664 age- and sex-matched control subjects. Stepwise logistic regression
      uncovered five GWAS-identified SNPs at five loci that also showed significant
      associations in our case-control cohort. These five SNPs were included in the
      risk model and also applied to calculation of the polygenic risk score (PRS). The
      area under the curve determined with the leave-one-out cross-validation method
      was 0.63 (95% confidence interval, 0.60-0.66) or 0.61 (0.58-0.64) for versions of
      the model that did or did not include cigarette smoking and family history of
      pancreatic cancer in addition to the five SNPs, respectively. Individuals in the
      lowest and highest quintiles for the PRS had odds ratios of 0.62 (0.42-0.91) and
      1.98 (1.42-2.76), respectively, for pancreatic cancer development compared with
      those in the middle quintile. We have thus developed a risk model for pancreatic
      cancer that showed moderately good discriminatory ability with regard to
      differentiation of pancreatic cancer patients from control individuals. Our
      findings suggest the potential utility of a risk model that incorporates
      replicated GWAS-identified SNPs and established demographic or environmental
      factors for the identification of individuals at increased risk for pancreatic
      cancer development.

PMID- 30192809
TI  - Long-term apoptosis-related protein expression in the diabetic mouse ovary.
AB  - Emerging evidence has shown that oocytes from diabetic ovaries exhibit delayed
      maturation, mitochondrial dysfunction and meiotic defects, which are related
      increased apoptosis. The main objective of the present study was to analyze the
      apoptosis pathways activated during follicular loss at multiple time points in a
      diabetic mouse model. Twenty BALB/c mice were used in this study, and diabetes
      mellitus was induced by streptozotocin injection. Three diabetic and two control
      animals were sacrificed on days 15, 20, 70 and 80 posttreatment. The ovaries were
      then removed; one was used for follicular counting, TUNEL, immunohistochemistry
      and immunofluorescence, while the other was used for Western blot analysis. The
      proteins studied were BAX, BCL2, t-BID, FAS, FASL, active caspase 8, active
      caspase 9 and active caspase 3. Follicular apoptosis decreased over time, with
      the highest values observed at 15 days posttreatment. Granulosa cells were
      positive for active caspase 3, which showed constant expression levels at all
      time points. FAS, FASL, t-BID and active caspase 8 showed strong cytoplasmic
      immunostaining in the oocytes and granulosa cells of the diabetic mice, with
      significant increases observed at 15, 20 and 70 days posttreatment. BAX
      expression was slightly higher in the diabetic mouse ovaries than in the control
      ovaries at 15, 20 and 70 days posttreatment, whereas the highest active caspase 9
      expression was at observed 20 days posttreatment. Low BCL2 protein levels were
      detected in the diabetic mouse ovaries at all time points. This study describes
      for the first time the behavior of apoptosis-related proteins in the diabetic
      mouse ovary and shows not only that the FAS/FASL pathway contributes to
      follicular loss but also that antral follicles are the most affected.

PMID- 30192810
TI  - Rice dwarf virus infection alters green rice leafhopper host preference and
      feeding behavior.
AB  - Host plants, pathogens and their herbivore vectors systems have complex
      relationships via direct and indirect interactions. Although there are
      substantial gaps in understanding these systems, the dynamics of the
      relationships may influence the processes of virus transmission and plant disease
      epidemics. Rice dwarf virus (RDV) is mainly vectored by green rice leafhoppers
      (GRLHs), Nephotettix cincticeps (Uhler) (Hemiptera: Cicadellidae) in a
      persistently circulative manner. In this study, host plant selection preferences
      of non-viruliferous and viruliferous (carrying RDV) GRLHs between RDV-free and
      RDV-infected plants were tested. Non-viruliferous GRLHs preferred RDV-infected
      rice plants over RDV-free rice plants, and viruliferous GRLHs preferred RDV-free
      rice plants over RDV-infected rice plants. In odor selection preference bioassay
      using a four-field olfactometer, non-viruliferous GRLHs preferred odors of RDV
      infected rice plants over healthy rice and viruliferous GRLHs preferred odors of
      RDV-free rice plants over RDV-infected ones. In 6 h plant penetration behavior
      bioassay using electrical penetration graphs, non-viruliferous GRLHs spent
      shorter time in non-penetration and much longer time in xylem feeding on RDV
      infected, compared to RDV-free rice plants. Viruliferous GRLHs exhibited more
      salivation and stylet movement on RDV-free rice plants than on RDV-infected rice
      plants. We infer from these findings that RDV influences these vector behaviors
      by altering host plant physiology to promote viral transmission.

PMID- 30192601
TI  - Elliptic Flow of Charm and Strange Hadrons in High-Multiplicity p+Pb Collisions
      at sqrt[s_{NN}]=8.16  TeV.
AB  - The elliptic azimuthal anisotropy coefficient (v_{2}) is measured for charm
      (D^{0}) and strange (K_{S}^{0}, Lambda, Xi^{-}, and Omega^{-}) hadrons, using a
      data sample of p+Pb collisions collected by the CMS experiment, at a nucleon
      nucleon center-of-mass energy of sqrt[s_{NN}]=8.16  TeV. A significant positive
      v_{2} signal from long-range azimuthal correlations is observed for all particle
      species in high-multiplicity p+Pb collisions. The measurement represents the
      first observation of possible long-range collectivity for open heavy flavor
      hadrons in small systems. The results suggest that charm quarks have a smaller
      v_{2} than the lighter quarks, probably reflecting a weaker collective behavior.
      This effect is not seen in the larger PbPb collision system at sqrt[s_{NN}]=5.02 
      TeV, also presented.

PMID- 30192812
TI  - Angioarchitecture and hemodynamics of microvascular arterio-venous malformations.
AB  - INTRODUCTION: Arteriovenous malformations (AVMs) are characterized by
      pathological high flow, low resistance connections between arteries and veins.
      Treatment is critically dependent on correct interpretation of angioarchitectural
      features. However, some microfistular AVMs do not match the characteristics
      described in current AVM classification systems. Therefore, we propose a new
      subgroup of microfistular AVMs, composed of enlarged, fistulous paths on the
      venous half of capillaries and/or dilated draining venules (hyperdynamic,
      capillary-venulous malformation [CV-AVM]). CV-AVMs still ensure arterial flow to
      the periphery and fistulous venous drainage is less pronounced than in classical
      AVMs such that these lesions are often misinterpreted as venous malformations.
      MATERIALS AND METHODS: We developed a computational model to study the effects of
      microvascular anomalies on local hemodynamics, as well as their impact on
      angiographic contrast propagation. Flow rates and pressures were computed with a
      lumped parameter description, while contrast propagation was determined by
      solving the 1D advection-diffusion equation. RESULTS AND CONCLUSIONS: For the
      newly proposed CV-AVM angioarchitecture, the computational model predicts
      increased arterio-venous contrast agent transit times and highly dispersive
      transport characteristics, compared to microfistular, interstitial type IV AVMs
      and high flow type II and III AVMs. We related these findings to time-contrast
      intensity curves sampled from clinical angiographies and found that there is
      strong evidence for the existence of CV-AVM.

PMID- 30192813
TI  - Comparative genomics, infectivity and cytopathogenicity of Zika viruses produced
      by acutely and persistently infected human hematopoietic cell lines.
AB  - Zika virus (ZIKV), an arthropod-borne virus, has emerged as a major human
      pathogen. Prolonged or persistent ZIKV infection of human cells and tissues may
      serve as a reservoir for the virus and present serious challenges to the safety
      of public health. Human hematopoietic cell lines with different developmental
      properties revealed differences in susceptibility and outcomes to ZIKV infection.
      In three separate studies involving the prototypic MR 766 ZIKV strain and the
      human monocytic leukemia U937 cell line, ZIKV initially developed only a low
      grade infection at a slow rate. After continuous culture for several months,
      persistently ZIKV-infected cell lines were observed with most, if not all, cells
      testing positive for ZIKV antigen. The infected cultures produced ZIKV RNA (v
      RNA) and infectious ZIKVs persistently ("persistent ZIKVs") with distinct
      infectivity and pathogenicity when tested using various kinds of host cells. When
      the genomes of ZIKVs from the three persistently infected cell lines were
      compared with the genome of the prototypic MR 766 ZIKV strain, distinct sets of
      mutations specific to each cell line were found. Significantly, all three
      "persistent ZIKVs" were capable of infecting fresh U937 cells with high
      efficiency at rapid rates, resulting in the development of a new set of
      persistently ZIKV-infected U937 cell lines. The genomes of ZIKVs from the new set
      of persistently ZIKV-infected U937 cell lines were further analyzed for their
      different mutations. The 2nd generation of persistent ZIKVs continued to possess
      most of the distinct sets of mutations specific to the respective 1st generation
      of persistent ZIKVs. We anticipate that the study will contribute to the
      understanding of the fundamental biology of adaptive mutations and selection
      during viral persistence. The persistently ZIKV-infected human cell lines that we
      developed will also be useful to investigate critical molecular pathways of ZIKV
      persistence and to study drugs or countermeasures against ZIKV infections and
      transmission.

PMID- 30192814
TI  - Prognostic utility of serum free light chain ratios and heavy-light chain ratios
      in multiple myeloma in three PETHEMA/GEM phase III clinical trials.
AB  - We investigated the prognostic impact and clinical utility of serum free light
      chains (sFLC) and serum heavy-light chains (sHLC) in patients with multiple
      myeloma treated according to the GEM2005MENOS65, GEM2005MAS65, and GEM2010MAS65
      PETHEMA/GEM phase III clinical trials. Serum samples collected at diagnosis were
      retrospectively analyzed for sFLC (n = 623) and sHLC (n = 183). After induction
      or autologous transplantation, 309 and 89 samples respectively were available for
      sFLC and sHLC assays. At diagnosis, a highly abnormal (HA) sFLC ratio (sFLCr)
      (<0.03 or >32) was not associated with higher risk of progression. After therapy,
      persistence of involved-sFLC levels >100 mg/L implied worse survival (overall
      survival [OS], P = 0.03; progression-free survival [PFS], P = 0.007). Among
      patients that achieved a complete response, sFLCr normalization did not
      necessarily indicate a higher quality response. We conducted sHLC investigations
      for IgG and IgA MM. Absolute sHLC values were correlated with monoclonal protein
      levels measured with serum protein electrophoresis. At diagnosis, HA-sHLCrs
      (<0.29 or >73) showed a higher risk of progression (P = 0.006). Additionally,
      involved-sHLC levels >5 g/L after treatment were associated with shorter survival
      (OS, P = 0.001; PFS, P = 0.018). The HA-sHLCr could have prognostic value at
      diagnosis; absolute values of involved-sFLC >100 mg/L and involved-sHLC >5 g/L
      could have prognostic value after treatment.

PMID- 30192811
TI  - Adipose-derived stem cell-mediated paclitaxel delivery inhibits breast cancer
      growth.
AB  - Breast cancer represents the main malignancy in women and autologous fat grafting
      is a diffuse procedure in the management of post-surgical breast defects causing
      patients' psychosocial problems, with high costs for the public health. Recently,
      beneficial effects of fat grafting during post-surgical breast reconstruction
      have been amplified from the enrichment with human adipose-derived stem cells
      (ASCs) present in the stromal vascular fraction (SVF) of adult adipose tissue
      isolated during intraoperatory procedures. The major concern about the ASC
      enrichment during post-surgery breast reconstruction depends on their potential
      ability to release growth factors and hormones that can promote proliferation of
      residual or quiescent cancer cells, with the risk of de novo cancer development
      or recurrence. The recent description that adult stem cells primed in vitro may
      be vehicle for anti-cancer drug delivery offers a new vision concerning the role
      of ASCs in breast reconstruction after cancer surgery. Paclitaxel (PTX) is a
      chemotherapeutic agent acting as a microtubule-stabilizing drug inhibiting cancer
      cell mitotic activity. We optimized PTX loading and release in cultured ASCs and
      then analyzed the effects of PTX-loaded ASCs and their conditioned medium on CG5
      breast cancer survival, proliferation and apoptosis in vitro, and inCG5 xenograft
      in vivo. We documented that ASCs can uptake and release PTX in vitro, with slight
      cytotoxic effects. Interestingly, PTX-loaded ASCs in co-culture, as well as
      conditioned medium alone, inhibited CG5 cell proliferation and survival in vitro
      and xenograft tumor growth in vivo. The antitumor effect of PTX-loaded ASCs may
      offer a new perspective concerning the use of ASCs during breast reconstruction
      becoming an additional local preventive chemotherapeutic agent against tumor
      recurrence. However, further experiments in vitro and in vivo are needed to
      collect more evidence confirming the efficacy and safety in cancer patients.

PMID- 30192815
TI  - Novel robust control of a 7-DOF exoskeleton robot.
AB  - This paper proposes a novel robust control method for the control of a 7-DOF
      exoskeleton robot. The external disturbances and unknown dynamics in the form of
      friction forces, different upper-limb's mass, backlash, and input saturation make
      robot unstable, which prevents the robot from correctly following the defined
      path. A new fractional sliding mode controller (NFSMC) is designed, which is
      robust against unknown dynamic and external disturbances. Fractional PID
      controller (FPID) has high trajectory tracking, but it is not robust against
      external disturbances. Therefore, by combining NFSMC and FPID controllers, a new
      compound fractional PID sliding mode controller (NCFPIDSMC) is proposed, which
      benefits high trajectory tracking of FPID and robustness of NFSMC. The stability
      of the proposed control method is verified by Lyapunov theory. A random noise is
      applied in order to confirm the robustness of the proposed control method.

PMID- 30192816
TI  - Timing of adverse events among voluntary medical male circumcision clients:
      Implications from routine service delivery in Zimbabwe.
AB  - BACKGROUND: Timing of routine follow-up visits after adult male circumcision (MC)
      differs by country and method. Most men do not attend all routine follow-up
      visits. This cross-sectional study aimed to further understanding of AE timing
      within a large-scale, routine, MC program to improve patient safety. METHODS:
      From 2013-2017, ZAZIC consortium performed 192,575 MCs in Zimbabwe; the reported
      adverse event (AE) rate was 0.3%. Three scheduled, routine, follow-up visits
      intend to identify AEs. For surgical MC, visits were days 2, 7 and 42 post
      procedure. For PrePex (device-based), visits were days 7, 14 and 49. Descriptive
      statistics explored characteristics of those patients with AEs. For each MC
      method, chi-square tests were used to evaluate associations between AE timing
      (days from MC to AE diagnosis) and factors of interest (age, AE type, severity).
      RESULTS: Of 421 AEs, 290 (69%) were surgical clients: 55 (19%) AEs were <=2 days
      post-MC; 169 (58%) between 3-7 days; 47 (16%) between days 8-14; and 19 (7%) were
      >=15 post-MC. Among surgical clients, bleeding was most common AE on/before Day 2
      while infections predominated in other follow-up periods (p<0.001). Younger
      surgical MC patients with AEs experienced AEs later than older clients (p<0.001).
      Among 131 (31%) PrePex clients with AEs, 46 (35%) were <=2 days post-MC; 59 (45%)
      between 3-7 days; 16 (12%) between days 8-14; and 10 (7%) >=15 post-MC. For
      PrePex clients, device displacements were more likely to occur early while late
      AEs were most commonly infections (p<0.001). CONCLUSION: Almost 23% of surgical
      and 8% of PrePex AEs occurred after Visit 2. Later AEs were likely infections.
      Clinicians, clients, and caregivers should be more effectively counseled that
      complications may arise after initial visits. Messages emphasizing attention to
      wound care until complete healing could help ensure client safety. Younger boys,
      ages 10-14, and their caregivers would benefit from improved, targeted, post
      operative counseling.

PMID- 30192817
TI  - Stability of histone post-translational modifications in samples derived from
      liver tissue and primary hepatic cells.
AB  - Chromatin structure, a key contributor to the regulation of gene expression, is
      modulated by a broad array of histone post-translational modifications (PTMs).
      Taken together, these "histone marks" comprise what is often referred to as the
      "histone code". The quantitative analysis of histone PTMs by mass spectrometry
      (MS) offers the ability to examine the response of the histone code to
      physiological signals. However, few studies have examined the stability of
      histone PTMs through the process of isolating and culturing primary cells. To
      address this, we used bottom-up, MS-based analysis of histone PTMs in liver,
      freshly isolated hepatocytes, and cultured hepatocytes from adult male Fisher
      F344 rats. Correlations between liver, freshly isolated cells, and primary
      cultures were generally high, with R2 values exceeding 0.9. However, a number of
      acetylation marks, including those on H2A K9, H2A1 K13, H3 K4, H3 K14, H4 K8, H4
      K12 and H4 K16 differed significantly among the three sources. Inducing
      proliferation of primary adult hepatocytes in culture affected several marks on
      histones H3.1/3.2 and H4. We conclude that hepatocyte isolation, culturing and
      cell cycle status all contribute to steady-state changes in the levels of a
      number of histone PTMs, indicating changes in histone marks that are rapidly
      induced in response to alterations in the cellular milieu. This has implications
      for studies aimed at assigning biological significance to histone modifications
      in tumors versus cancer cells, the developmental behavior of stem cells, and the
      attribution of changes in histone PTMs to altered cell metabolism.

PMID- 30192822
TI  - Evaluation of cytotoxicity features of antimicrobial peptides with potential to
      control bacterial diseases of citrus.
AB  - Antimicrobial peptides (AMPs) can be found in various organisms, and could be
      considered an alternative for pesticides used to control plant pathogens,
      including those affecting citrus. Brazil is the largest producer and exporter of
      frozen concentrated orange juice in the world. However, the citrus industry has
      been affected by several diseases such as citrus canker and huanglongbing (HLB),
      caused by the bacteria Xanthomonas citri subsp. citri (X.citri) and Candidatus
      Liberibacter asiaticus (CaLas), respectively. In order to control these
      pathogens, putative AMPs were prospected in databases containing citrus
      sequences. Furthermore, AMPs already reported in the literature were also used
      for in vitro and in vivo assays against X.citri. Since CaLas cannot be cultivated
      in vitro, surrogates as Sinorhizobium meliloti and Agrobacterium tumefaciens were
      used. This study reports the evaluation of six AMPs obtained from different
      sources, two of them from Citrus spp. (citrus-amp1 and citrus-amp2), three from
      amphibians (Hylin-a1, K0-W6-Hy-a1 and Ocellatin 4-analogue) and one from porcine
      (Tritrpticin). Peptides K0-W6-Hy-a1, Ocellatin 4-analogue, and citrus-amp1 showed
      bactericidal activity against X.citri and S. meliloti and bacteriostatic effect
      on A. tumefaciens. These results were confirmed for X.citri in planta. In
      addition cytotoxicity evaluations of these molecules were performed. The AMPs
      that showed the lowest hemolytic activities were Triptrpticin, citrus-amp1 and
      citrus-amp2. Citrus-amp1 and citrus-amp2 not presented toxicity in experiments
      using in vivo model, G. mellonella and U87 MG cells. To verify the interaction of
      these AMPs with bacteria and erythrocyte cell membranes, vesicles mimicking these
      cells were built. Citrus-amp1 and Tritrpticin exhibited higher affinity to
      bacterial membranes, while Ocellatin 4-analogue and Hylin-a1 showed higher
      affinity to erythrocyte membranes; exclude their use in citrus. This work
      demonstrates an essential alternative, trough AMPs obtained from Citrus spp.,
      which can be feasibly used to control bacterial pathogens.

PMID- 30192819
TI  - Diagnostic performance of choline PET/CT for the detection of bone metastasis in
      prostate cancer: A systematic review and meta-analysis.
AB  - PURPOSE: The aim of this study was to evaluate the diagnostic performance of
      choline positron emission tomography/computed tomography (PET/CT) for the
      detection of bone metastasis in patients with prostate cancer. METHODS: MEDLINE,
      EMBASE and the Cochrane Library were searched up to 20 February 2018 for studies
      that used 11C-choline or 18F-choline PET/CT for the detection of bone metastasis
      in patients with prostate cancer and "histopathology and/or clinical follow-up"
      as the reference standard. Methodological quality was assessed using the Quality
      Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Pooled diagnostic
      accuracy with the 95% confidence interval (CI) was calculated using a bivariate
      random effects model. We also constructed hierarchical summary receiver operating
      characteristic curves and performed meta-regression analyses. RESULTS: Fourteen
      studies with reasonable methodological quality were included in the analysis. On
      a per-patient basis, the pooled sensitivity, specificity, positive likelihood
      ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR)
      were 0.89 (95% CI 0.80-0.94), 0.98 (95% CI 0.95-0.99), 40.4 (95% CI 19.7-82.6),
      0.12 (95% CI 0.07-0.20), and 344 (95% CI 148-803), respectively. On a per-lesion
      basis, the pooled sensitivity, specificity, PLR, NLR, and DOR were 0.91 (95% CI
      0.85-0.94), 0.97 (95% CI 0.95-0.98), 34.1 (95% CI 20.0-58.1), 0.10 (95% CI 0.06
      0.16), and 358 (95% CI 165-778), respectively. In the meta-regression analysis,
      the clinical setting (staging vs. restaging) was the only source of study
      heterogeneity on a per-patient basis. CONCLUSIONS: Choline PET/CT shows excellent
      diagnostic performance for the detection of bone metastasis. However, a negative
      choline PET/CT result cannot ensure the lack of bone metastasis.

PMID- 30192823
TI  - Fibroblast growth factor23 is associated with axonal integrity and neural network
      architecture in the human frontal lobes.
AB  - Elevated levels of FGF23 in individuals with chronic kidney disease (CKD) are
      associated with adverse health outcomes, such as increased mortality, large
      vessel disease, and reduced white matter volume, cardiovascular and
      cerebrovascular events. Apart from the well-known link between cardiovascular
      (CV) risk factors, especially diabetes and hypertension, and cerebrovascular
      damage, elevated FGF23 is also postulated to be associated with cerebrovascular
      damage independently of CKD. Elevated FGF23 predisposes to vascular calcification
      and is associated with vascular stiffness and endothelial dysfunction in the
      general population with normal renal function. These factors may lead to
      microangiopathic changes in the brain, cumulative ischemia, and eventually to the
      loss of white matter fibers. The relationship between FGF23 and brain integrity
      in individuals without CKD has hitherto not been investigated. In this study, we
      aimed to determine the association between FGF23, and white matter integrity in a
      cohort of 50 participants with varying degrees of CV risk burden, using high
      resolution structural human brain connectomes constructed from MRI diffusion
      images. We observed that increased FGF23 was associated with axonal loss in the
      frontal lobe, leading to a fragmentation of white matter network organization.
      This study provides the first description of the relationship between elevated
      levels of FGF23, white matter integrity, and brain health. We suggest a
      synergistic interaction of CV risk factors and FGF23 as a potentially novel
      determinant of brain health.

PMID- 30192818
TI  - Utilization of dried blood spot specimens can expedite nationwide surveillance of
      HIV drug resistance in resource-limited settings.
AB  - INTRODUCTION: Surveillance of HIV drug resistance (HIVDR) is crucial to ensuring
      the continued success of antiretroviral therapy (ART) programs. With the concern
      of reduced genotyping sensitivity of HIV on dried blood spots (DBS), DBS for
      HIVDR surveillance have been limited to ART-naive populations. To investigate if
      DBS under certain conditions may also be a feasible sample type for HIVDR testing
      in ART patients, we piloted nationwide surveys for HIVDR among ART patients using
      DBS in two African countries with rapid scale-up of ART. METHODS: EDTA-venous
      blood was collected to prepare DBS from adult and pediatric ART patients
      receiving treatment during the previous 12-36 months. DBS were stored at ambient
      temperature for two weeks and then at -80 degrees C until shipment at ambient
      temperature to the WHO-designated Specialized HIVDR Laboratory at CDC in Atlanta.
      Viral load (VL) was determined using NucliSENS EasyQ(r) HIV-1 v2.0 kits; HIVDR
      genotyping was performed using the ATCC HIV-1 Drug Resistance Genotyping kits.
      RESULTS: DBS were collected from 1,368 and 1,202 ART patients; 244 and 255 these
      specimens had VL >=1,000 copies/mL in Kenya and Tanzania, respectively. The
      overall genotyping rate of those DBS with VL >=1,000 copies/mL was 93.0% (95% CI:
      89.1%-95.6%) in Kenya and 91.8% (87.7%-94.6%) in Tanzania. The turnaround times
      for the HIVDR surveys from the time of collecting DBS to completing laboratory
      testing were 6.5 months and 9.3 months for the Kenya and Tanzania surveys,
      respectively. CONCLUSIONS: The study demonstrates a favorable outcome of using
      DBS for nationwide surveillance of HIVDR in ART patients. Our results confirm
      that DBS collected and stored at ambient temperature for two weeks, and shipped
      with routine courier services are a reliable sample type for large-scale
      surveillance of acquired HIVDR.

PMID- 30192820
TI  - The prevalence of antibodies against the HLA-DRB3 protein in kidney
      transplantation and the correlation with HLA expression.
AB  - Human leukocyte antigen (HLA)-DRB3 is a functional HLA class II gene, which has a
      limited allele diversity in the human population. Furthermore, the HLA-DRB3 gene
      is only present in a subset of individuals. Therefore, in organ transplantation,
      this HLA molecule is frequently mismatched between patient and graft donor and
      thus antibodies against this mismatched HLA molecule can develop. In this study,
      we aimed to evaluate the prevalence and reactivity of these antibodies and aimed
      to identify factors that underlie antibody formation against HLA-DRB3. We showed
      in our patient cohort that HLA-DRB3 antibodies are identified in about 7% of all
      patients that were screened with solid phase assays. In these assays, we observed
      multiple antibody reactivity patterns indicating that HLA-DRB3 harbours multiple
      epitopes. In those cases, where we succeeded at tracing back the induction of
      these antibodies to the molecular HLA typing of the immunogenic event, we noticed
      a different frequency of HLA-DRB1 allele groups in the donors as compared to a
      control group. To a certain extent this distribution (e.g. HLA-DRB1*11
      individuals) could be linked to an altered expression level. However, it also
      appears that different HLA-DRB3 alleles (e.g. HLA-DRB3*01 group) vary in their
      immunogenicity without having an expression difference. In conclusion, our study
      provides information on the immunogenicity and reactivity patterns of antibodies
      against HLA-DRB3 in kidney transplantation, and it points towards the possibility
      of HLA expression as a factor underlying antibody formation.

PMID- 30192824
TI  - Anticardiolipin (aCL) in sera from periodontitis subjects activate Toll-like
      receptor 4 (TLR4).
AB  - Anticardiolipin antibodies (aCL) have been reported to be present in 15-20% of
      sera from subjects with periodontitis at concentrations exceeding those found in
      95% of the healthy adult population. These antibodies, albeit at concentrations
      exceeding those generally found in periodontitis subjects, are typically present
      in patients with the antiphospholipid syndrome (APS), an autoimmune disease
      characterized by thrombosis and recurrent pregnancy loss. aCL from APS patients
      are proinflammatory and can activate trophoblasts, macrophages, and platelets via
      cell-surface interactions with their target antigen beta-2-glycoprotein-I
      (beta2GPI). beta2GPI is an anionic phospholipid-binding serum protein that can
      associate with toll-like receptors (TLR's) on the cell-surface, leading to cell
      activation following interaction with autoimmune aCL. We examined an expanded
      series of 629 sera from clinically characterized subjects for aCL content, and
      observed that 14-19% of these sera contained elevated (>95th %-tile) levels of
      aCL. We purified IgG from 16 subjects with elevated or normal levels of aCL and
      examined their ability to activate TLR2- or TLR4-transfected human embryonic
      kidney (HEK) cells, and observed that IgG from periodontitis patients with
      elevated aCL activated HEK-TLR4 cells, but not HEK-TLR2 cells. Prior removal of
      aCL by immunoabsorption significantly reduced the ability of IgG preparations
      from these sera to activate TLR4. Further experiments using a human first
      trimester trophoblastic cell line (HTR8 sv/neo) revealed that aCL from
      periodontitis patients stimulated IL-8 production, which was profoundly decreased
      if aCL was removed by immunoabsorption or if HTR8 sv/neo were pretreated with
      blocking anti-TLR4 antibodies. Thus, it appears that aCL from periodontitis
      patients can be proinflammatory, activating cells via TLR4. Since these
      antibodies are likely produced via molecular mimicry due to similarities between
      oral bacterial antigens and beta2GPI, the data indicate that circulating serum
      aCL may induce or influence inflammatory responses at sites distant from the oral
      cavity.

PMID- 30192825
TI  - Evaluating the progress to eliminate mother-to-child transmission (MTCT) of
      syphilis in Hunan Province, China: A study based on a health service delivery
      model.
AB  - To prevent mother-to-child transmission (MTCT) of syphilis, Hunan Province
      launched a free syphilis screening and treatment programme in 2011. Thus far, the
      programme has been implemented for 6 years. This study aimed to assess progress
      toward the elimination of MTCT of syphilis in Hunan Province from 2011-2016.
      Estimates of syphilis-related adverse pregnancy outcomes (APOs) were based on the
      health service delivery model developed by the WHO, which were then translated
      into disability-adjusted life years (DALYs). Default values in the model were
      replaced by a Chinese version. The progress of this programme was assessed
      through the reduction of estimated DALYs with and without screening and treatment
      services. The results showed that the estimated number of syphilis-related APOs
      in Hunan Province from 2011 to 2016 was 3,840, more than 70% of which occurred
      among women who had at least one antenatal care visit but were not screened or
      treated for syphilis during pregnancy. The public health burden resulting from
      maternal syphilis-related APOs was 192,528 DALYs over six years, and with the
      current screening and treatment coverage, approximately 163,794 expected DALYs
      (46%) were averted. Our estimates indicate that in Hunan Province, syphilis in
      pregnancy continues to be an important cause of APOs, which can lead to
      substantial perinatal morbidity and mortality. Approximately half of the expected
      public health burden resulting from syphilis-related APOs was averted by the
      current screening and treatment services, which suggests progress toward the
      elimination of MTCT of syphilis in Hunan Province.

PMID- 30192821
TI  - Failure to detect functional transfer of active K-Ras protein from extracellular
      vesicles into recipient cells in culture.
AB  - Exosomes, extracellular nanovesicles that carry nucleic acids, lipids, and
      proteins, have been the subject of several studies to assess their ability to
      transfer functional cargoes to cells. We recently characterized extracellular
      nanovesicles released from glioblastoma cells that carry active Ras in complex
      with proteins regulating exosome biogenesis. Here, we investigated whether a
      functional transfer of Ras from exosomes to other cells can initiate
      intercellular signaling. We observed that treatment of serum-starved, cultured
      glioblastoma cells with exogenous glioblastoma exosomes caused a significant
      increase in cellular viability over time. Moreover, we detected fluorescent
      signal transfer from lipophilic dye-labeled exogenous glioblastoma exosomes into
      cultured glioblastoma cells. To probe possible signaling from cell-to-cell, we
      utilized bimolecular luciferase complementation to examine the ability of K-Ras
      in exosomes to interact with the Raf-Ras Binding domain (Raf-RBD) expressed in a
      recipient cell line. Although the K-Ras/Raf-RBD interaction was readily
      detectable upon co-expression in a single cell line, or following lysis of co
      cultured cell lines separately expressing K-Ras and RBD, bearing in mind the
      limitations of our assay, we were unable to detect the interaction in the intact,
      co-cultured cell lines or upon treatment of the Raf-RBD-expressing cells with
      exosomes containing K-Ras. Furthermore, HA-Tag-BFP fused to the K-Ras
      hypervariable region and CAAX sequence failed to be transferred at significant
      levels from extracellular vesicles into recipient cells, but remained detectable
      in the cell supernatants even after 96 hours of culture of naive cells with
      extracellular vesicles. We conclude that if transfer of functional K-Ras from
      extracellular vesicles into the cytoplasm of recipient cells occurs, it must do
      so at an extremely low efficiency and therefore is unlikely to initiate Ras-ERK
      MAP kinase pathway signaling. These results suggest that studies claiming
      functional transfer of protein cargoes from exosomes should be interpreted with
      caution.

PMID- 30192826
TI  - Correction: Acheulean technology and landscape use at Dawadmi, central Arabia.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0200497.].

PMID- 30192827
TI  - Putative probiotic lactic acid bacteria isolated from sauerkraut fermentations.
AB  - Probiotics are live microorganisms which confer health benefits to the host, and
      may be isolated from several sources, such as vegetable foodstuffs. Sauerkraut is
      a cabbage product resulting from fermentation by a lactic acid bacteria microbial
      succession, and is a potential source for probiotics. The aim of the present
      study was the isolation and characterization of probiotic microorganisms from
      sauerkraut fermentations. Four distinct fermentations were performed, from which
      lactic acid bacteria were recovered. Overall, 114 isolates were obtained,
      phenotypically and genotypically characterized, identified to the genus level and
      evaluated regarding safety and probiotic potential. Representative bacteria were
      selected for further analysis, 52% being Lactobacillus spp. and 33% belonging to
      Leuconostoc spp. genus. One isolate revealed to be beta-hemolytic, 42% possessed
      potentially mobile antimicrobial resistance, 88% were resistant to bile and 20%
      to low pH. The six most promising candidates were further characterized and
      presented antimicrobial activity against Listeria monocytogenes, three being
      resistant to lower pH values. Thus, global analysis of data gathered during this
      study highlighted the identification of three Lactobacillus strains with putative
      probiotic potential, suggesting the applicability of sauerkraut fermentations as
      a source for probiotic isolation. Due to their origin these strains should be
      suited for future application in the food industry, namely vegetable products
      such as sauerkraut itself.

PMID- 30192828
TI  - Attitude, perception, willingness, motivation and barriers to practice-based
      research: A cross-sectional survey of hospital pharmacists in Lahore, Punjab,
      Pakistan.
AB  - BACKGROUND AND OBJECTIVES: Practice-based research (PBR) is of pivotal importance
      for hospital pharmacists which not only up-grades the profession but also
      improves the patient care. This study aimed to evaluate the attitude, perception,
      willingness, motivation and barriers to PBR among hospital pharmacists in
      Pakistan. METHODS: A descriptive, cross sectional study design was employed. Data
      were collected between 1st December, 2017 and 1st March, 2018 from 130 hospital
      pharmacists employed in 41 hospitals of Lahore, Pakistan. A survey instrument
      comprising of six sections was designed to determine the attitude, perception,
      willingness, motivation and barriers to PBR. Data were analyzed by using
      Statistical Package for Social Sciences (IBM SPSS Statistics for Windows, version
      21.0, Armonk, NY: IBM Corp.). The normality of the data was determined through
      Shapiro-Wilks and Kolmogorov-Smirnov tests. Independent Samples Mann-Whitney U
      Test and Independent Samples Kruskal-Wallis Test were carried out to test if
      there were differences among the characteristics of the hospital pharmacists.
      Logistic regression analysis was used to figure out the factors associated with
      attitude, perceptions, willingness and motivation towards PBR. A p-value <0.05
      was used for statistical significance of differences. RESULTS: A total of 141
      pharmacists were approached. Among them, 130 responded to the survey (response
      rate 92%). Out of a maximum score i.e., 5 (100%) the respondents obtained a
      median score of 4 (IQR = 0) for attitude, perception and motivation towards PBR;
      whereas, a median score of 4 (IQR = 1) was obtained for willingness thus
      demonstrating fair positive attitude, good perceptions, increased motivation and
      willingness towards PBR. The most common barrier limiting the pharmacists'
      participation in PBR was lack of time (23.8%) followed by lack of incentives
      (16.2%) and lack of support (14.6%). Results of the logistic regression analysis
      revealed that hospital pharmacists practicing in the inpatient settings had 4.56
      times more positive attitude towards PBR (OR = 4.56, 95%CI = 1.07?19.42, p-value
      = 0.040) as compared to those practicing in the outpatient settings. The male
      hospital pharmacists (OR = 8.86, 95%CI = 1.15-53.74, p-value = 0.017), those
      practicing in the outpatient (OR = 23.51, 95%CI = 2.04?271.53, p-value = 0.011)
      and inpatient settings had increased motivation towards PBR (OR = 12.24, 95%CI =
      1.61?94.66, p-value = 0.016). CONCLUSION: Despite the presence of several
      barriers, the respondents had fair positive attitude, good perceptions, increased
      motivation and willingness towards PBR which is a promising finding.

PMID- 30192829
TI  - Twitter use in scientific communication revealed by visualization of information
      spreading by influencers within half a year after the Fukushima Daiichi nuclear
      power plant accident.
AB  - Scientific communication through social media, particularly Twitter has been
      gaining importance in recent years. As such, it is critical to understand how
      information is transmitted and dispersed through outlets such as Twitter,
      particularly in emergency situations where there is an urgent need to relay
      scientific information. The purpose of this study is to examine how original
      tweets and retweets on Twitter were used to diffuse radiation related information
      after the Fukushima Daiichi nuclear power plant accident. Out of the Twitter
      database, we purchased all tweets (including replies) and retweets related to
      Fukushima Daiichi nuclear power plant accident and or radiation sent from March
      2nd, 2011 to September 15th, 2011. This time frame represents the first six
      months after the East Japan earthquake, which occurred on March 11th, 2011. Using
      the obtained data, we examined the number of tweets and retweets and found that
      only a small number of Twitter users were the source of the original posts that
      were retweeted during the study period. We have termed these specific accounts as
      "influencers". We identified the top 100 influencers and classified the contents
      of their tweets into 3 groups by analyzing the document vectors of the text.
      Then, we examined the number of retweets for each of the 3 groups of influencers,
      and created a retweet network diagram to assess how the contents of their tweets
      were being spread. The keyword "radiation" was mentioned in over 24 million
      tweets and retweets during the study period. Retweets accounted for roughly half
      (49.7%) of this number, and the top 2% of Twitter accounts defined as
      "influencers" were the source of the original posts that accounted for 80.3% of
      the total retweets. The majority of the top 100 influencers had individual
      Twitter accounts bearing real names. While retweets were intensively diffused
      within a fixed population, especially within the same groups with similar
      document vectors, a group of influencers accounted for the majority of retweets
      one month after the disaster, and the share of each group did not change even
      after proven scientific information became more available.

PMID- 30192830
TI  - Two-stage revision arthroplasty for Mycobacterium Tuberculosis periprosthetic
      joint infection: An outcome analysis.
AB  - BACKGROUND: Mycobacterium tuberculosis periprosthetic joint infection (TBPJI) is
      a rare complication of hip/knee joint arthroplasty. The outcomes of hip/knee
      TBPJI treatment are still unreported. The objective of this study was to
      investigate the outcomes of hip/knee TBPJI following treatment with two-stage
      exchange arthroplasty. MATERIALS AND METHODS: From 2003 to 2013, 11 patients with
      TBPJI (six hips and five knees) were treated with two-stage exchange arthroplasty
      at our institution. We collected and analyzed variables including demographic
      data, comorbidities, microbiological data, duration of symptoms, and types of
      antibiotic used in bone cement. RESULTS: At the most recent follow-up, the
      success rate of two-stage exchange arthroplasty was 63.3% (7 of 11). All five
      knee treatments resulted in infection eradication and successful prosthesis
      reimplantation. However, only two hip TBPJI treatments resulted in successful
      outcomes; two patients died and two experienced chronic infection. Overall,
      secondary bacterial infections were common in patients with TBPJI (5 of 11 cases,
      45.5%). Streptomycin in bone cement increased the success rate (83.33% vs. 40%).
      CONCLUSION: More than one third of the patients treated with two-stage exchange
      arthroplasty for TBPJI showed infection relapse or uncontrolled infection.
      Streptomycin-loaded interim cement spacers appeared to help ensure successful
      treatment. Routine M. tuberculosis culture is recommended when treating TBPJI in
      areas of high tuberculosis prevalence.

PMID- 30192831
TI  - Safety and immune responses after intradermal application of Porcilis PRRS in
      either the neck or the perianal region.
AB  - The objective of the present study was to assess safety and immune responses in
      gilts after intradermal application of Porcilis(r) PRRS in two different
      application sites under field conditions. Forty-four gilts were allocated to one
      of three groups: Gilts of group 1 (n = 10) served as non-vaccinated controls,
      gilts of group 2 (n = 17) were vaccinated intradermally in the neck and gilts of
      group 3 (n = 17) received an intradermal vaccination in the perianal region.
      Clinical observations, local injection site reactions and histopathologic
      examination of the injection site were used for safety assessments. Frequency and
      degree of clinical signs were not significantly different between all three
      groups. Minor local reactions for both vaccination groups were observed; however,
      at 6, 7, 8, 9 and 15 days post-vaccination (dpv), the mean injection site
      reaction score was significantly lower in pigs vaccinated in the perianal region.
      In histopathologic examination, an extended inflammatory dimension was observed
      more frequently in pigs vaccinated in the neck. Blood samples were analyzed to
      quantify the post-vaccination humoral (ELISA and virus neutralization test) and
      cellular (IFN-gamma ELISPOT) immune responses. PRRSV-specific antibodies were
      present in the serum of all vaccinated animals from 14 dpv onwards, whereas all
      control pigs remained negative throughout the study. Neutralizing antibody titers
      were significantly higher in pigs vaccinated in the perianal region at 28 dpv. At
      14, 21 and 28 dpv, PRRSV-specific IFN-gamma secreting cells were significantly
      increased in both vaccination groups compared to non-vaccinated gilts. Analysis
      of mean numbers of PRRSV-specific IFN-gamma secreting cells did not result in
      statistically significant differences between both vaccination groups. The
      results of this study indicate that the perianal region is a safe alternative
      application site for intradermal vaccination of gilts with Porcilis PRRS.
      Furthermore, the intradermal application of Porcilis PRRS induced humoral and
      cellular immune responses independent of the administration site.

PMID- 30192832
TI  - The utility of two interview-based physical activity questionnaires in healthy
      young adults: Comparison with accelerometer data.
AB  - BACKGROUND: Accurate assessment of physical activity is essential to determine
      the magnitude of the health-related benefits of regular physical activity. While
      physical activity questionnaires are easy to use, their accuracy in comparison to
      objective measures has been questioned. The purpose of the present study was to
      examine the utility of two interview-based questionnaires; a recently-developed
      instrument, the Simple Physical Activity Questionnaire (SIMPAQ), and the Seven
      Day-Physical Activity Recall (7DPAR). METHODS: Accelerometer data was collected
      in 72 university students (50% females). Telephone interviews were conducted to
      complete the SIMPAQ and the 7DPAR. RESULTS: Significant correlations (p < .001)
      were found between accelerometer-based moderate-to-vigorous physical activity
      (MVPA), the amount of self-reported moderate-to-vigorous exercise assessed via
      the SIMPAQ (rho = .49), and vigorous physical activity assessed via the 7DPAR
      (rho = .50). Exercise assessed via the SIMPAQ was significantly correlated with
      the vigorous physical activity score of the 7DPAR (rho = .56, p < .001). While
      participants needed three minutes less to complete the SIMPAQ (p < .001),
      participants tended to be more confident about the accuracy of the answers they
      provided on the 7DPAR (p < .01). CONCLUSIONS: These two questionnaire measures of
      physical activity performed similarly in a healthy young adult sample. The SIMPAQ
      can be completed in 15 minutes, which could be an advantage in settings where
      time for physical activity assessment is limited.

PMID- 30192834
TI  - Development and validation of an ensemble classifier for real-time recognition of
      cow behavior patterns from accelerometer data and location data.
AB  - Behaviors are important indicators for assessing the health and well-being of
      dairy cows. The aim of this study is to develop and validate an ensemble
      classifier for automatically measuring and distinguishing several behavior
      patterns of dairy cows from accelerometer data and location data. The ensemble
      classifier consists of two parts, our new Multi-BP-AdaBoost algorithm and a data
      fusion method based on D-S evidence theory. We identify seven behavior patterns:
      feeding, lying, standing, lying down, standing up, normal walking, and active
      walking. Accuracy, sensitivity, and precision were used to validate
      classification performance. The Multi-BP-AdaBoost algorithm performed well when
      identifying lying (92% accuracy, 93% sensitivity, 82% precision), lying down
      (99%, 82%, 86%), standing up (99%, 74%, 85%), normal walking (97%, 92%, 86%), and
      active walking (99%, 94%, 89%). Its results were poor for feeding (80%, 52%, 55%)
      and standing (80%, 46%, 58%), which are difficult to differentiate using a leg
      mounted sensor. Position data made it possible to differentiate feeding and
      standing. The D-S evidence fusion method for combining accelerometer data and
      location data in classification was used to fuse two pieces of basic behavior
      related evidence into a single estimation model. With this addition, the
      sensitivity and precision of the two difficult behaviors increased by
      approximately 20 percentage points. In conclusion, the classification results
      indicate that the ensemble classifier effectively recognizes various behavior
      patterns in dairy cows. However, further work is needed to study the robustness
      of the feature and model by increasing the number of cows enrolled in the trial.

PMID- 30192833
TI  - Alginate encapsulated multipotent adult progenitor cells promote corneal stromal
      cell activation via release of soluble factors.
AB  - To reduce the increasing need for corneal transplantation, attempts are currently
      aiming to restore corneal clarity, one potent source of cells are multipotent
      adult progenitor cells (MAPC(r)). These cells release a powerful cocktail of
      paracrine factors that can guide wound healing and tissue regeneration. However,
      their role in corneal regeneration has been overlooked. Thus, we sought to
      explore the potential of combining the cytoprotective storage feature of
      alginate, with MAPC to generate a storable cell-laden gel for corneal wound
      healing. 72 hours following hypothermic storage, alginate encapsulation was shown
      to maintain MAPC viability at either 4 or 15 degrees C. Encapsulated MAPC (2 x106
      cells/mL) stored at 15 degrees C presented the optimum temperature that allowed
      for cell recovery. These cells had the ability to reattach to tissue culture
      plastic whilst exhibiting normal phenotype and this was maintained in serum-free
      and xenobiotic-free medium. Furthermore, corneal stromal cells presented a
      significant decrease in scratch-wounds in the presence of alginate encapsulated
      MAPC compared to a no-cell control (p = 0.018). This study shows that
      immobilization of MAPC within an alginate hydrogel does not hinder their ability
      to affect a secondary cell population via soluble factors and that these effects
      are successfully retained following hypothermic storage.

PMID- 30192836
TI  - Family and the field: Expectations of a field-based research career affect
      researcher family planning decisions.
AB  - Field-based data collection provides an extraordinary opportunity for comparative
      research. However, the demands of pursuing research away from home creates an
      expectation of unburdened individuals who have the temporal, financial, and
      social resources to conduct this work. Here we examine whether this myth of the
      socially unencumbered scholar contributes to the loss of professionals and
      trainees. To investigate this, we conducted an internet-based survey of
      professional and graduate student anthropologists (n = 1025) focused on the
      challenges and barriers associated with developing and maintaining a fieldwork
      oriented career path and an active family life. This study sought to determine
      how (1) family socioeconomic status impacts becoming an anthropologist, (2)
      expectations of field-based research influence family planning, and (3) fieldwork
      experiences influence perceptions of family-career balance and stress. We found
      that most anthropologists and anthropology students come from educated households
      and that white men were significantly more likely to become tenured professionals
      than other demographic groups. The gender disparity is striking because a larger
      number of women are trained in anthropology and were more likely than men to
      report delaying parenthood to pursue their career. Furthermore, regardless of
      socioeconomic background, anthropologists reported significant lack of family
      career balance and high stress associated with the profession. For professionals,
      lack of balance was most associated with gender, age, SES, tenure, and impacts of
      parenting on their career, while for students it was ethnicity, relative degree
      speed, graduate funding, employment status, total research conducted, career
      impact on family planning, and concern with tenure (p < .05). Anthropology
      bridges the sciences and humanities, making it the ideal discipline to initiate
      discussions on the embedded structural components of field-based careers
      generalizable across specialties.

PMID- 30192835
TI  - Cyclooxygenase pathway mediates the inhibition of Na-glutamine co-transporter
      B0AT1 in rabbit villus cells during chronic intestinal inflammation.
AB  - In the mammalian intestine, glutamine assimilation by the absorptive villus cells
      is mediated by Na-glutamine co-transport, specifically by B0AT1. In a rabbit
      model of chronic intestinal inflammation, B0AT1 is inhibited secondary to a
      decrease in the number of co-transporters in the brush border membrane (BBM).
      This inhibition can be reversed by treatment with a broad-spectrum immune
      modulator such as glucocorticoid suggesting that immune inflammatory mediators
      may regulate B0AT1 during chronic intestinal inflammation. Arachidonic acid (AA)
      metabolites (AAM) are increased during chronic intestinal inflammation. However,
      whether AAM may regulate B0AT1 during chronic intestinal inflammation is unknown.
      Treatment of rabbits with ATK, to prevent the release of AAM reversed the
      inhibition of B0AT1. AAM are products of cyclooxygenase (COX) and/or lipoxygenase
      (LOX) pathways. Inhibition of COX with piroxicam, therefore reduction of
      prostaglandin formation in the chronically inflamed intestine, reversed the
      inhibition of B0AT1 to its normal levels. In contrast, inhibition of LOX with
      MK886, thus reduction of leukotriene formation during chronic enteritis, did not
      affect the inhibition of B0AT1. Kinetic studies showed that the mechanism of
      restoration of B0AT1 by ATK or piroxicam was secondary to the restoration of BBM
      co-transporter numbers. Western Blot analysis also demonstrated restoration of
      BBM B0AT1 co-transporter numbers. In conclusion, this study demonstrates that Na
      glutamine co-transport mediated by B0AT1 in villus cells is regulated by
      prostaglandins rather than leukotrienes in the chronically inflamed intestine.

PMID- 30192838
TI  - Alien leaf beetles (Coleoptera, Chrysomelidae) of European Russia and some
      general tendencies of leaf beetle invasions.
AB  - Invasions of leaf beetles can cause tremendous economic consequences because some
      of these insects become major pests in invaded territories. We present the first
      inventory of alien Chrysomelidae of European Russia that appeared in the region
      in the 20th and 21st centuries (9 species) with analysis of the history of their
      invasions and detailed maps of distribution. This case study revealed some
      general tendencies of invasions of leaf beetles: (1) Recently, a dramatic
      increase in the rate of Chrysomelidae invasions is observed, which reflects the
      increase in international trade of living plants; (2) Alien leaf beetles can
      spread quickly, occupying almost all of Europe within several decades; (3) When
      the range of some leaf beetle species is quickly expanding, or when the species
      has been recorded established somewhere outside the native range, this species
      should be regarded as a potential invader worldwide. and (4) Alien leaf beetles
      usually occur on alien or cultivated plants, but some become naturalized in
      native communities. The specific information was the following. Two species
      native to the Mediterranean region, Chrysolina americana (feeds on Rosmarinus and
      Lavandula) and Leptomona erythrocephala (feeds on Lotus corniculatus) were
      recorded in European Russia for the first time. A polyphagous pest of
      floriculture Luperomorpha xanthodera native to China and Korea and a pest of
      soybeans Medythia nigrobilineata native to east Asia have been in the region
      since 2016. A pest of tobacco Epitrix hirtipennis native to North America has
      occurred since 2011. A pest of corn Diabrotica virgifera was intercepted at the
      border of Russia in 2011 but has not established. Three alien species have been
      in the region since the 20th century: Zygogramma suturalis introduced from North
      America for control of Ambrosia, Phyllotreta reitteri native to Afghanistan and
      Tajikistan and feeding on Lepidium latifolium, and the Colorado potato beetle
      Leptinotarsa decemlineata.

PMID- 30192837
TI  - Short-term low salinity mitigates effects of oil and dispersant on juvenile
      eastern oysters: A laboratory experiment with implications for oil spill response
      activities.
AB  - Following the Deepwater Horizon oil spill, eastern oyster (Crassostrea virginica)
      reefs in the northern Gulf of Mexico were exposed to oil and various associated
      clean-up activities that may have compromised oyster reef health. Included in the
      exposure was oil, dispersant, and in some locales, atypical salinity regimes. Oil
      and dispersants can be detrimental to oysters and the effects of salinity depend
      on the level. In addition to these extrinsic factors, genetic diversity of oyster
      populations may help the oysters respond to stressors, as demonstrated in other
      systems. We used a 3*3*2 factorial design to experimentally examine the effects
      of oil/dispersed oil, intraspecific genetic diversity, and salinity on juvenile
      (ca. 25 mm shell height) oyster survivorship and growth during a 21-d exposure in
      a closed, recirculating system. The genetic effect was weak overall, oil and
      dispersed oil negatively affected juvenile oyster survivorship, and low salinity
      mitigated mortality in oil and dispersed oil treatments. Survivorship was about
      40% greater in low-salinity than in mesohaline water for both oil and dispersed
      oil treatments, bringing survivorship in low salinity oil-only treatments to a
      similar level with low salinity controls (no oil). Oyster growth was minimal
      after 21 d but appeared to be negatively affected by oil and dispersed oil, and
      had a significant interaction with salinity. Our results may be informative for
      future decisions regarding oil spill response activities and suggest that a pulse
      of low salinity water may be a viable short-term mitigation option for oysters if
      filtration characteristics, exposure time, and water temperatures are all
      considered, in addition to weighing the costs and benefits of this type of
      response on other organisms and habitats.

PMID- 30192839
TI  - Assessing the performance of only HRP2 and HRP2 with pLDH based rapid diagnostic
      tests for the diagnosis of malaria in middle Ghana, Africa.
AB  - BACKGROUND: Rapid diagnostic test (RDT) kits have been useful tools to screen for
      the presence of infection with malaria parasites. Despite the improvement, false
      results from RDTs present a greater challenge. The need for quality test kits is
      desirable. We evaluated the diagnostic accuracy of three malaria RDTs. METHOD:
      The team consented and enrolled 754 participants from the two major public
      hospitals in Kintampo districts of Ghana from June 2014 to August 2014. Venous
      blood samples were obtained by trained personnel and samples were screened for
      malaria using CareStart and SD Bioline HRP2 and HRP2 with pLDH based RDTs with
      blood slides for malaria microscopy as "gold standard". Geometric mean parasite
      densities were estimated and parasite densities were used to estimate the
      quantitative limits of the RDTs. The sensitivities, specificities and other
      performance criteria were calculated using statistical analytical software.
      RESULT: The median age of participants was 21 (range 5-31) years. There were
      28.6% (215/752) were males and 71.4% (537/752) were females. Comparing with
      microscopy, the sensitivity, specificity, positive predictive value, negative
      predictive value and the ROC were for CareStart (HRP2), 98.2%, 66.5%, 82.6%,
      95.6%, 0.82; for CareStart (HRP2/pLDH) 98.2%, 66.5%, 82.6%, 95.6%, 0.82 and for
      SD-Bioline (HRP2/pLDH) RDTs 98.2%, 69.2%, 84.2%, 96.0%, 0.84 respectively. The
      performance for all the kits were acceptable at a cut-off of 25 or more
      parasites/MUl of blood. CONCLUSIONS: The diagnostic performance of the three
      malaria RDTs was acceptable, according to the World Health Organisation criteria,
      to detect densities >=25 parasite/MUl of blood. The RDTs with HRP2/pLDH targets
      were comparable to those with only HRP2 and could successfully substitute current
      and commonly used HRP2-based RDTs.

PMID- 30192840
TI  - The molecular structure of Schistosoma mansoni PNP isoform 2 provides insights
      into the nucleoside selectivity of PNPs.
AB  - Purine nucleoside phosphorylases (PNPs) play an important role in the blood fluke
      parasite Schistosoma mansoni as a key enzyme of the purine salvage pathway. Here
      we present the structural and kinetic characterization of a new PNP isoform from
      S. mansoni, SmPNP2. Thermofluorescence screening of different ligands suggested
      cytidine and cytosine are potential ligands. The binding of cytosine and cytidine
      were confirmed by isothermal titration calorimetry, with a KD of 27 MUM for
      cytosine, and a KM of 76.3 MUM for cytidine. SmPNP2 also displays catalytic
      activity against inosine and adenosine, making it the first described PNP with
      robust catalytic activity towards both pyrimidines and purines. Crystal
      structures of SmPNP2 with different ligands were obtained and comparison of these
      structures with the previously described S. mansoni PNP (SmPNP1) provided clues
      for the unique capacity of SmPNP2 to bind pyrimidines. When compared with the
      structure of SmPNP1, substitutions in the vicinity of SmPNP2 active site alter
      the architecture of the nucleoside base binding site thus permitting an
      alternative binding mode for nucleosides, with a 180 degrees  rotation from the
      canonical binding mode. The remarkable plasticity of this binding site enhances
      our understanding of the correlation between structure and nucleotide
      selectivity, thus suggesting new ways to analyse PNP activity.

PMID- 30192841
TI  - The limits of the foreign language effect on decision-making: The case of the
      outcome bias and the representativeness heuristic.
AB  - Language context (native vs. foreign) affects people's choices and preferences in
      a wide variety of situations. However, emotional reactions are a key component
      driving people's choices in those situations. In six studies, we test whether
      foreign language context modifies biases and the use of heuristics not directly
      caused by emotional reactions. We fail to find evidence that foreign language
      context modifies the extent to which people suffer from outcome bias (Experiment
      1a & 1b) and the use of the representativeness heuristic (Experiment 2a & 2b).
      Furthermore, foreign language context does not modulate decision-making in those
      scenarios even when emotion is brought into the context (Experiment 1c & 2c).
      Foreign language context shapes decision-making, but the scope of its effects
      might be limited to decision-making tendencies in which emotion plays a causal
      role.

PMID- 30192842
TI  - Use of machine learning to predict cognitive performance based on brain
      metabolism in Neurofibromatosis type 1.
AB  - Neurofibromatosis Type 1 (NF1) can cause a wide range of cognitive deficits, but
      its underlying nature is still unknown. We investigated the correlation between
      cognitive performance and specific patterns of resting-state brain metabolism in
      a NF1 sample. Sixteen individuals diagnosed with NF1 underwent 18F-FDG PET/CT
      brain imaging followed by a neuropsychological assessment. Principal component
      analysis was performed on 17 measures of cognitive function and a machine
      learning approach based on Gaussian Process Regression was used to individually
      predict the components that represented most of the variance in the
      neuropsychological data. The accuracy of the method was estimated using leave-one
      out cross-validation and its significance through permutation testing. We found
      that only the first component could be accurately predicted from resting state
      metabolism (r = 0.926, p<0.001). Multiple and heterogeneous measures contribute
      to the first component, mainly WISC/WAIS Procedure and Verbal IQ, verbal memory
      and fluency. Considering the accurate prediction of measures of
      neuropsychological performance based on brain metabolism in NF1 patients, this
      suggests an underlying metabolic pattern that relates to cognitive performance in
      this group.

PMID- 30192843
TI  - Designing a trapping strategy to aid Giant African Snail (Lissachatina fulica)
      eradication programs.
AB  - In pest eradication programs, traps can directly reduce pest populations;
      however, their application to gastropod programs remains relatively unexplored.
      The South Florida Giant African Snail, Liassachatina fulica (Pulmonata:
      Achatinidae), eradication program allowed a realistic evaluation of their
      utility. Field studies were conducted to determine the best bait, barrier and
      trap for use during the eradication program. Immature and adult snails were
      attracted to banana fruit and a commercially produced bait but only the
      commercially produced bait did not attract non-target and pest mammals. Four
      commercially produced traps and 4 barriers were field evaluated for snail
      retention efficacy. Snails escaped all traps and trap/barrier combinations but
      the rate of escape ranged from 10-100% after 24 hrs. Laboratory studies confirmed
      that snails can survive crossing a 5 cm barrier of copper tape, salt, insect
      stickem or antifouling paint. In the laboratory study snails did not cross copper
      sulfate but they crossed the barrier in the field. Adding salt to traps as a
      means to retain snails reduced the number of snails trapped. Laboratory studies
      confirmed that dry salt decreased the number of snails entering traps and snails
      did not enter traps when the salt was dissolved in water. Two trap types and the
      commercial bait were selected for a large-scale program test. For three months,
      trapping along with hand collection and pesticide application were conducted on
      114 properties in five locations. Traps caught snails when surveys and regular
      pesticide applications on the same properties did not detect them. On 21
      occasions snails were only found in traps, and both immature and adult snails
      were caught. This study showed that traps could be effectively deployed in an
      eradication program and they could capture snails that may have escaped other
      control measures.

PMID- 30192845
TI  - Optimisation of curvilinear external shading of windows in cellular offices.
AB  - Shading of windows influences building cooling and heating loads through control
      of solar heat gains, and lighting load through access to available daylight.
      Shading shape thus presents an important factor both in building energy analysis
      and building aesthetics. Curvilinearity of solar paths suggests that the optimal
      shading shape may be curvilinear as well, and our aim here is to test this
      expectation. To accommodate curvilinearity of shading shape, outer edges of
      shading, which consists of overhang, western and eastern fins, are modeled as non
      uniform rational basis spline (NURBS) curves, a widely accepted representation
      standard for curves in design industry. As a case study, a cellular office is
      considered in the Pacific Northwest National Laboratory (PNNL) office building
      model, with its overhang lined up by seven control points, and the fins lined up
      by five control points each, with two ending control points joint for the
      overhang and the fins. With control points allowed to take on nine different
      alternative depths, genetic optimisation is employed for 16 representative USA
      climates with respect to total equivalent source energy for heating, cooling and
      lighting loads. The main finding is that in a very close proximity to optimal
      shadings found by genetic optimisation there exist shadings with much simpler
      control point structure, obtained by identifying depths of successive control
      points, that have nearly rectangular overhangs. Since the difference between
      these simpler shadings and the optimal ones is less than 0.24%, this partially
      rejects the expectation that the optimal shading shape should be curvilinear.
      Structure of these near-optimal shadings also suggests a new way to partition
      shadings into independent regions: the lower and the upper parts of the western
      fin, joints of the overhang with the western and the eastern fin, the interior
      part of the overhang and the rest of the eastern fin.

PMID- 30192844
TI  - Potentiometric titration for the high precision determination of active
      components in six types of chemical disinfectants.
AB  - Chemical disinfectants effectively kill pathogenic microorganisms, eliminating
      routes of transmission for infectious diseases. Accurate quantification of the
      active ingredients can help make a more effective use of disinfectants. In this
      study, the active ingredients in six different types of chemical disinfectants
      were systematically quantified with great precision and accuracy using
      potentiometric titration. The coefficient of variations fell in the range of
      0.04%-0.46%. The recovery rates of samples were all above 95% and the extended
      uncertainty was 0.32g/L. This method can be broadly applied to the analysis of
      disinfectants in the future.

PMID- 30192846
TI  - Prodrugs for colon-restricted delivery: Design, synthesis, and in vivo evaluation
      of colony stimulating factor 1 receptor (CSF1R) inhibitors.
AB  - The ability to restrict low molecular weight compounds to the gastrointestinal
      (GI) tract may enable an enhanced therapeutic index for molecular targets known
      to be associated with systemic toxicity. Using a triazolopyrazine CSF1R inhibitor
      scaffold, a broad range of prodrugs were synthesized and evaluated for enhanced
      delivery to the colon in mice. Subsequently, the preferred cyclodextrin prodrug
      moiety was appended to a number of CSF1R inhibitory active parent molecules,
      enabling GI-restricted delivery. Evaluation of a cyclodextrin prodrug in a
      dextran sodium sulfate (DSS)-induced mouse colitis model resulted in enhanced GI
      tissue levels of active parent. At a dose where no significant depletion of
      systemic monocytes were detected, the degree of pharmacodynamic effect-measured
      as reduction in macrophages in the colon-was inferior to that observed with a
      systemically available positive control. This suggests that a suitable
      therapeutic index cannot be achieved with CSF1R inhibition by using GI-restricted
      delivery in mice. However, these efforts provide a comprehensive frame-work in
      which to pursue additional gut-restricted delivery strategies for future GI
      targets.

PMID- 30192847
TI  - Transgenic Metarhizium pingshaense synergistically ameliorates pyrethroid
      resistance in wild-caught, malaria-vector mosquitoes.
AB  - Transgenic Metarhizium pingshaense expressing the spider neurotoxin Hybrid (Met
      Hybrid) kill mosquitoes faster and at lower spore doses than wild-type strains.
      In this study, we demonstrate that this approach dovetails with the cornerstone
      of current malaria control: pyrethroid-insecticides, which are the cornerstone of
      current malaria control. We used World Health Organization (WHO) tubes, to
      compare the impact on insecticide resistance of Met-Hybrid with red fluorescent
      M. pingshaense (Met-RFP), used as a proxy for the wild-type fungus. Insecticides
      killed less than 20% of Anopheles coluzzii and Anopheles gambiae s.s. mosquitoes
      collected in a malaria endemic region of Burkina Faso where pyrethroid use is
      common. Seven days post-infection, mortality for insecticide-sensitive and
      resistant mosquitoes averaged 94% with Met-Hybrid and 64% with Met-RFP, with LT80
      values of 5.32+/-0.199 days and 7.76+/-0.183 days, respectively. Eighty nine
      percent of insecticide-resistant mosquitoes exposed to permethrin five days post
      infection with Met-Hybrid died within 24 hours: only 22% died from Met-Hybrid
      alone over this 24-hour period. Compared to Met-RFP, Met-Hybrid also
      significantly reduced flight capacity of mosquitoes 3 to 5 days post-infection.
      Based on WHOPES phase I laboratory susceptibility bioassays, transgenic Met
      Hybrid provides effective biological control for adult African malaria vectors
      that may be used to synergistically manage insecticide resistance with current
      methods.

PMID- 30192849
TI  - Comparative evaluation of Salmonella Typhimurium vaccines derived from UK-1 and
      14028S: Importance of inherent virulence.
AB  - The initial virulence and invasiveness of a bacterial strain may play an
      important role in leading to a maximally efficacious attenuated live vaccine.
      Here we show that chi9909, derived from Salmonella Typhimurium UK-1 chi3761 (the
      most virulent S. Typhimurium strain known to us), is effective in protecting mice
      against lethal UK-1 and 14028S (less virulent S. Typhimurium strain) challenge.
      As opposed to this, 14028S-derived vaccine chi12359 induces suboptimal levels of
      protection, with survival percentages that are significantly lower when
      challenged with lethal UK-1 challenge doses. T-cell assays have revealed that
      significantly greater levels of Th1 cytokines IFN-gamma and TNF-alpha were
      secreted by stimulated T-lymphocytes obtained from UK-1(DeltaaroA) immunized mice
      than those from mice immunized with 14028S(DeltaaroA). In addition, UK
      1(DeltaaroA) showed markedly higher colonizing ability in the spleen, liver, and
      cecum when compared to 14028S(DeltaaroA). Enumeration of bacteria in fecal
      pellets has also revealed that UK-1(DeltaaroA) can persist in the host for over
      10 days whereas 14028S(DeltaaroA) titers dropped significantly by day 10.
      Moreover, co-infection of parent strains UK-1 and 14028S resulted in considerably
      greater recovery of the former in multiple mucosal and gut associated lymphatic
      tissues. Mice immunized with UK-1(DeltaaroA) were also able to clear UK-1
      infection remarkably more efficiently from the target organs than
      14028S(DeltaaroA). Together, these results provide ample evidence to support the
      hypothesis that attenuated derivatives of parent strains with higher initial
      virulence make better vaccines.

PMID- 30192848
TI  - Influenza infection directly alters innate IL-23 and IL-12p70 and subsequent IL
      17A and IFN-gamma responses to pneumococcus in vitro in human monocytes.
AB  - IMPORTANCE: Influenza virus is highly contagious and poses substantial public
      health problems due to its strong association with morbidity and mortality.
      Approximately 250,000-500,000 deaths are caused by seasonal influenza virus
      annually, and this figure increases during periods of pandemic infections. Most
      of these deaths are due to secondary bacterial pneumonia. Influenza-bacterial
      superinfection can result in hospitalisation and/or death of both patients with
      pre-existing lung disease or previously healthy individuals. The importance of
      our research is in determining that influenza and its component haemagglutinin
      has a direct effect on the classic pneumococcus induced pathways to IL-17A in our
      human ex vivo model. Our understanding of the mechanism which leaves people
      exposed to influenza infection during superinfection remain unresolved. This
      paper demonstrates that early infection of monocytes inhibits an arm of immunity
      crucial to bacterial clearance. Understanding this mechanism may provide
      alternative interventions in the case of superinfection with antimicrobial
      resistant strains of bacteria.

PMID- 30192593
TI  - Search for Low-Mass Dijet Resonances Using Trigger-Level Jets with the ATLAS
      Detector in pp Collisions at sqrt[s]=13  TeV.
AB  - Searches for dijet resonances with sub-TeV masses using the ATLAS detector at the
      Large Hadron Collider can be statistically limited by the bandwidth available to
      inclusive single-jet triggers, whose data-collection rates at low transverse
      momentum are much lower than the rate from standard model multijet production.
      This Letter describes a new search for dijet resonances where this limitation is
      overcome by recording only the event information calculated by the jet trigger
      algorithms, thereby allowing much higher event rates with reduced storage needs.
      The search targets low-mass dijet resonances in the range 450-1800 GeV. The
      analyzed data set has an integrated luminosity of up to 29.3  fb^{-1} and was
      recorded at a center-of-mass energy of 13 TeV. No excesses are found; limits are
      set on Gaussian-shaped contributions to the dijet mass distribution from new
      particles and on a model of dark-matter particles with axial-vector couplings to
      quarks.

PMID- 30192851
TI  - Policy makers' perspective on the provision of maternal health services via
      mobile health clinics in Tanzania-Findings from key informant interviews.
AB  - OBJECTIVE: To explore the operational feasibility of using mobile health clinics
      to reach the chronically underserved population with maternal and child health
      (MCH) services in Tanzania. DESIGN: We conducted fifteen key informant interviews
      (KIIs) with policy makers and district health officials to explore issues related
      to mobile health clinic implementation and their perceived impact. MAIN RESULTS:
      Policy makers' perspective indicates that mobile health clinics have improved
      coverage of essential maternal and child health interventions; however, they face
      financial, human resource-related and logistic constraints. Reported are the
      increased engagement of the community and awareness of the importance of MCH
      services, which is believed to have a positive effect on uptake of services. Key
      informants (KIs)' perceptions and opinions were generally in favour of the mobile
      clinics, with few cautioning on their potential to provide care in a manner that
      promotes a continuum of care. Immunization, antenatal care, postnatal care and
      growth monitoring all seem to be successfully implemented in this mode of service
      delivery. Nevertheless, all informants perceive mobile clinics as a resource
      intensive yet unavoidable mode of service delivery given the current situation of
      having women and children residing in remote settings. CONCLUSION: While the
      government shows the clear motive, the need and the willingness to continue
      providing services in this mode, the plan to sustain them is still a puzzle. We
      argue that the continuing need for these services should go hand in hand with
      proper planning and resource mobilization to ensure that they are being
      implemented holistically and to promote the provision of quality services and
      continuity of care. Plans to evaluate their costs and effectiveness are crucial,
      and that will require the collection of relevant health information including
      outcome data to allow sound evaluations to take place.

PMID- 30192850
TI  - Fracture risk in type 2 diabetic patients: A clinical prediction tool based on a
      large population-based cohort.
AB  - BACKGROUND: An increased fracture risk has been described as a complication of
      Type 2 diabetes mellitus (T2DM). Clinical prediction models for general
      population have a limited predictive accuracy for fractures in T2DM patients. The
      aim was to develop and validate a clinical prediction tool for the estimation of
      5-year hip and major fracture risk in T2DM patients. METHODS AND RESULTS: A
      cohort of newly diagnosed T2DM patients (n = 51,143, aged 50-85, 57% men) was
      extracted from the Information System for the Development of Research in Primary
      Care (SIDIAP) database, containing computerized primary care records for >80% of
      the population of Catalonia, Spain (>6 million people). Patients were followed up
      from T2DM diagnosis until the earliest of death, transfer out, fracture, or end
      of study. Cox proportional hazards regression was used to model the 5-year risk
      of hip and major fracture. Calibration and discrimination were assessed. Hip and
      major fracture incidence rates were 1.84 [95%CI 1.64 to 2.05] and 7.12 [95%CI
      6.72 to 7.53] per 1,000 person-years, respectively. Both hip and major fracture
      prediction models included age, sex, previous major fracture, statins use, and
      calcium/vitamin D supplements; previous ischemic heart disease was also included
      for hip fracture and stroke for major fracture. Discrimination (0.81 for hip and
      0.72 for major fracture) and calibration plots support excellent internal
      validity. CONCLUSIONS: The proposed prediction models have good discrimination
      and calibration for the estimation of both hip and major fracture risk in
      incident T2DM patients. These tools incorporate key T2DM macrovascular
      complications generally available in primary care electronic medical records, as
      well as more generic fracture risk predictors. Future work will focus on
      validation of these models in external cohorts.

PMID- 30192852
TI  - In vitro effect of chlorambucil on human glioma cell lines (SF767 and U87-MG),
      and human microvascular endothelial cell (HMVEC) and endothelial progenitor cells
      (ECFCs), in the context of plasma chlorambucil concentrations in tumor-bearing
      dogs.
AB  - The objective of this study was to investigate a possible mechanism of action of
      metronomic chlorambucil on glioma by studying the in vitro cytotoxicity and anti
      angiogenic effects on glioma and endothelial cells, respectively. The in vitro
      LD50 and IC50 of chlorambucil were determined using human SF767 and U87-MG glioma
      cell lines, human microvascular endothelial cells (HMVECs) and human endothelial
      colony forming cells (ECFCs). Results were analyzed in the context of
      chlorambucil concentrations measured in the plasma of tumor-bearing dogs
      receiving 4 mg m-2 metronomic chlorambucil. The LD50 and IC50 of chlorambucil
      were 270 MUM and 114 MUM for SF767, and 390 MUM and 96 MUM for U87-MG,
      respectively. The IC50 of chlorambucil was 0.53 MUM and 145 MUM for the HMVECs
      and ECFCs, respectively. In pharmacokinetic studies, the mean plasma Cmax of
      chlorambucil was 0.06 MUM. Results suggest that metronomic chlorambucil in dogs
      does not achieve plasma concentrations high enough to cause direct cytotoxic or
      growth inhibitory effects on either glioma or endothelial cells.

PMID- 30192854
TI  - Correction: Sediment biomarkers elucidate the Holocene ontogeny of a shallow
      lake.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0191073.].

PMID- 30192858
TI  - Floristic and structural assessment of Australian rangeland vegetation with
      standardized plot-based surveys.
AB  - We describe and correlate environmental, floristic and structural vegetation
      traits of a large portion of Australian rangelands. We analysed 351 one hectare
      vegetation plots surveyed by Australia's Terrestrial Ecosystem Research Network
      (TERN) using the AusPlots Rangelands standardized method. The AusPlots Rangelands
      method involves surveying 1010 one meter-spaced point-intercepts (IPs) per plot.
      At each IP, species were scored, categorised by growth-form, converted to
      percentage cover as the input for the plot x species matrix. Vegetation structure
      is depicted by growth-form configuration and relative importance. The floristic
      and structural distance matrices were correlated with the Mantel test. Canonical
      correspondence analysis (CCA) related floristic composition to environmental
      variables sourced from WorldClim, the Atlas of Living Australia and TERN's Soil
      and Landscape Grid. Differences between clusters were tested with ANOVA while
      principal component analysis (PCA) ordered the plots within the environmental
      space. Our plot x species matrix required segmentation due to sparsity and high
      beta-diversity. Based on the ordination of plots latitude within environmental
      space, the matrix was segmented into three "superclusters": the winter rain and
      temperate Mediterranean, the monsoonal rain savannas and the arid deserts.
      Further classification, with the UPGMA linkage method, generated two, four and
      five clusters, respectively. All groupings are described by species richness,
      diversity indices and growth form conformation. Several floristic disjunctions
      were apparent and their possible causes are discussed. For all superclusters, the
      correspondence between the floristic and the structural or growth form matrices
      was statistically significant. CCA ordination clearly demarcated all groupings.
      Aridity, rainfall, temperature, seasonality, soil nitrogen and pH are significant
      correlates to the ordination of superclusters and clusters. At present, our
      results are influenced by incomplete sampling. As more sites are surveyed, this
      pioneer analysis will be updated and refined providing tools for the effective
      management of Australian rangelands.

PMID- 30192859
TI  - Time-resolved magnetic resonance angiography (TR-MRA) for the evaluation of post
      coiling aneurysms; A quantitative analysis of the residual aneurysm using full
      width at half-maximum (FWHM) value.
AB  - Magnetic resonance image (MRI) is now widely used for imaging follow-up for post
      coiling brain aneurysms. However, the accuracy on the estimation of residual
      aneurysm, which is crucial for the retreatment planning, remains to be
      controversial. The purpose of this study is to evaluate a new post-processing
      technique that provides improved estimation of the residual aneurysm after coil
      embolization. One hundred aneurysms on 93 patients who underwent coil
      embolization for brain aneurysm were evaluated using the 1.5 Tesla time-resolved
      magnetic resonance angiography (TR-MRA) one year after the treatment. To minimize
      the inter-observer variability caused by the window level adjustment, an
      automatic post processing protocol using the full-width at half-maximum (FWHM)
      value was utilized. The result was then compared with that from the conventional
      cerebral angiography. Of the 97 aneurysms that underwent both TR-MRA and DSA, 23
      (23.7%) showed residual neck / dome during follow-up. After window level
      adjustment, the size of the parent artery in the TR-MRA was consistent with that
      in the DSA. The reconstructed Volume Rendering images provided clear contours of
      the residual aneurysms and contributed to the understanding the configuration of
      residual aneurysm. The largest and the smallest diameter of the residual
      aneurysms was larger in the TR-MRA than in the DSA (8.05 vs. 7.72 mm, p = 0.0004;
      4.99 vs. 4.19 mm, p = 0.007 respectively). The sensitivity, specificity, and
      positive and negative predictive values of TR-MRA compared to DSA were 100%, 97%,
      73%, and 100%, respectively. Using the FWHM value to optimize the window level
      adjustment, the size of the residual component observed in the TR-MRA was larger
      compared to that in the DSA whereas the size of neck and the parent artery showed
      consistency between the two modalities. This image processing technique can be
      used as an effective screening tool for evaluating residual component in post
      coiling brain aneurysms.

PMID- 30192862
TI  - Lessons learned from twelve years of HIV Seroprevalence and Behavioral
      Epidemiology Risk Survey (SABERS) development and implementation among foreign
      militaries.
AB  - Circumstances within the military environment may place military personnel at
      increased risk of contracting sexually transmitted infections including HIV.
      Since 2005, RTI International has provided technical assistance to the
      Seroprevalence and Behavioral Epidemiology Risk Surveys (SABERS) program and
      supported the development and implementation of SABERS survey instruments in 18
      countries. RTI staff collaborated with the Department of Defense HIV/AIDS
      Prevention Program and host country military and health care leadership to
      develop a fully tested, culturally appropriate survey and data collection
      instrument and build local capacity by identifying and training local
      interviewers. We summarize the critical steps, challenges faced, and lessons
      learned from 12 years' experience developing, testing, and implementing SABERS
      instruments among military populations in Africa, Asia, and the Caribbean.

PMID- 30192853
TI  - Depression history and memory bias for specific daily emotions.
AB  - Reports of emotions experienced over the past week can be influenced by memory
      bias, which is more pronounced for people with depression. No studies, however,
      have examined memory bias for specific emotion clusters (e.g., sadness, anxiety,
      and anger) experienced on a day-to-day basis among people with depression or a
      history of depression. Participants (N = 1,657) from the Midlife in the United
      States Study were assessed for depression. Approximately 6 months later,
      participants reported their emotional experiences for 8 days and recalled these
      experiences on the final day. Differences in recalled and reported emotion were
      compared between participants with and without a history of depression.
      Participants overestimated experience only of negative emotions, particularly
      anger, and this negativity bias was greatest for participants with a history of
      depression. Feelings related to anger were prone to greater overestimation than
      sadness or anxiety. These findings emphasize the role of memory bias in
      retrospective reports of specific emotions and illustrate the presence of an
      amplified memory bias among people who are at a greater risk for recurrent
      depressive episodes.

PMID- 30192857
TI  - Impact of storage conditions on the quality of nucleic acids in paraffin embedded
      tissues.
AB  - RNA and DNA analyses from paraffin-embedded tissues (PET) are an important
      diagnostic tool for characterization of a disease, exploring biomarkers and
      treatment options. Since nucleic acids from formalin-fixed and paraffin-embedded
      (FFPE) tissue are of limited use for molecular analyses due to chemical
      modifications of biomolecules alternate, formalin-free fixation reagents such as
      the PAXgene Tissue system are of evolving interest. Furthermore, biomedical
      research and biomarker development critically relies on using long-term stored
      PET from medical archives or biobanks to correlate molecular features with long
      term disease outcomes. We therefore performed a comparative study to evaluate the
      effect of long term storage of FFPE and PAXgene Tissue-fixed and paraffin
      embedded (PFPE) tissue at different temperatures on nucleic acid stability and
      usability in PCR. Matched FFPE and PFPE human tissues from routine clinical
      setting or rat tissues from a highly controlled animal model were stored at room
      temperature and 4 degrees C, as well as in case of animal tissues frozen at -20
      degrees C and -80 degrees C. RNA and DNA were extracted in intervals for up to
      nine years, and examined for integrity, and usability in quantitative RT-PCR (RT
      qPCR) or PCR (qPCR) assays. PET storage at room temperature led to a degradation
      of nucleic acids which was slowed down by storage at 4 degrees C and prevented by
      storage at -20 degrees C or -80 degrees C. Degradation was associated with an
      amplicon length depending decrease of RT-qPCR and qPCR efficiency. Storage at 4
      degrees C improved amplifiability in RT-qPCR and qPCR profoundly. Chemically
      unmodified nucleic acids from PFPE tissue performed superior compared to FFPE
      tissue, regardless of storage time and temperature in both human and rat tissues.
      In conclusion molecular analyses from PET can be greatly improved by using a non
      crosslinking fixative and storage at lower temperatures such as 4 degrees C,
      which should be considered in prospective clinical studies.

PMID- 30192855
TI  - Periodic flashing coordinated reset stimulation paradigm reduces sensitivity to
      ON and OFF period durations.
AB  - Pathological synchronization in the basal ganglia network has been considered an
      important component of Parkinson's disease pathophysiology. An established
      treatment for some patients with Parkinson's disease is deep brain stimulation,
      in which a tonic high-frequency pulse train is delivered to target regions of the
      brain. In recent years, a novel neuromodulation paradigm called coordinated reset
      stimulation has been proposed, which aims to reverse the pathological synchrony
      by sequentially delivering short high-frequency bursts to distinct sub-regions of
      the pathologically synchronized network, with an average intra-burst interval for
      each sub-region corresponding to period of the pathological oscillation. It has
      further been proposed that the resultant desynchronization can be enhanced when
      stimulation is interrupted periodically, and that it is particularly beneficial
      to precisely tune the stimulation ON and OFF time-windows to the underlying
      pathological frequency. Pre-clinical and clinical studies of coordinated reset
      stimulation have relied on these proposals for their stimulation protocols. In
      this study, we present a modified ON-OFF coordinated reset stimulation paradigm
      called periodic flashing and study its behavior through computational modeling
      using the Kuramoto coupled phase oscillator model. We demonstrate that in
      contrast to conventional coordinated reset stimulation, the periodic flashing
      variation does not exhibit a need for precise turning of the ON-OFF periods to
      the pathological frequency, and demonstrates desynchronization for a wide range
      of ON and OFF periods. We provide a mechanistic explanation for the previously
      observed sensitivities and demonstrate that they are an artifact of the specific
      ON-OFF cycling paradigm used. As a practical consequence, the periodic flashing
      paradigm simplifies the tuning of optimal stimulation parameters by decreasing
      the dimension of the search space. It also suggests new, more flexible ways of
      delivering coordinated reset stimulation.

PMID- 30192856
TI  - The trend of resistance to antibiotics for ocular infection of Staphylococcus
      aureus, coagulase-negative staphylococci, and Corynebacterium compared with 10
      years previous: A retrospective observational study.
AB  - OBJECTIVE: To retrospectively identify epidemiological trends of infection on the
      ocular surface and investigate trends of resistance to bacterial antibiotics
      compared with 10-years previous for Staphylococcus aureus, coagulase-negative
      staphylococci (CNS), and Corynebacterium in Japan. MATERIALS AND METHODS:
      Bacterial isolate samples were collected from the conjunctival sacs of eyes
      afflicted with conjunctivitis, keratitis, dacryocystitis, and hordeolum from
      September 2004 through November 2005 (n = 145 isolates) and September 2014
      through November 2015 (n = 195 isolates) at the Baptist Eye Institute, Kyoto,
      Japan. The prevalence of methicillin-resistant S. aureus (MRSA), methicillin
      resistant CNS (MR-CNS), and fluoroquinolone-resistant Corynebacterium were
      examined, and susceptibility of isolated bacteria to levofloxacin (LVFX),
      cefmenoxime (CMX), chloramphenicol (CP), erythromycin (EM), vancomycin (VCM), and
      arbekacin (ABK) were compared between both time periods using the disc
      susceptibility method. RESULTS: Over the 10-year period from initial to final
      examination, the prevalence of MRSA and MR-CNS significantly decreased from 52%
      to 22% (P < 0.05) and from 47% to 25% (P < 0.05), respectively, yet there was no
      change in the prevalence of fluoroquinolone-resistant Corynebacterium (60% and
      54%; P = 0.38). Antibiotic-resistance trend analysis revealed that susceptibility
      to antibiotics in 2014-2015 was similar to that in 2004-2005. MRSA and MR-CNS
      were susceptible to CP (88%), VCM (100%), and ABK (100%), while fluoroquinolone
      resistant Corynebacterium was susceptible to CMX (100%), VCM (100%), and ABK
      (96%). CONCLUSION: The prevalence of MRSA and MR-CNS significantly decreased
      between the two time periods, yet more than 50% of the Corynebacterium isolates
      were still resistant to LVFX. Although no increase in bacterial resistance to
      antibiotics was found, a cautionary use of fluoroquinolone eye drops should be
      considered.

PMID- 30192863
TI  - Detection of betacyanin in red-tube spinach (Spinacia oleracea) and its
      biofortification by strategic hydroponics.
AB  - Betacyanins have been reported as water-soluble, nitrogenous pigments found in
      the order Caryophyllales, and they are known for powerful natural antioxidant.
      The biofortification of secondary metabolites such as anthocyanins and
      betacyanins has recently been performed in food crops by metabolic engineering
      through genetic modification. However, the distribution of genetically modified
      foods is strictly regulated. Therefore, we aimed to develop a new method for
      biofortifying natural antioxidants, betacyanins, without genetic modification. We
      first detected the presence of betacyanins in red-tube spinach (Spinacia
      oleracea) through ultraviolet-visible spectroscopy and mass spectrometry. We then
      hydroponically cultivated plants in the presence of three candidate compounds for
      betacyanin biofortification: dopamine, Ca2+, and sucrose. Liquid chromatography
      tandem mass spectrometry (LC-MS/MS) and antioxidant activity analyses showed that
      sucrose was most successful in biofortifying betacyanins, and reverse
      transcription polymerase chain reaction (RT-PCR) indicated that several genes
      involved in betacyanin biosynthesis were induced by sucrose. Therefore, strategic
      hydroponics represents a new approach for cultivating betacyanin-enriched
      vegetables.

PMID- 30192861
TI  - Home birth and its determinants among antenatal care-booked women in public
      hospitals in Wolayta Zone, southern Ethiopia.
AB  - INTRODUCTION: Antenatal care (ANC), health facility birth and postnatal care
      services are proved to reduce maternal and newborn morbidity and mortality. In
      Ethiopia, even though antenatal care coverage is good, still home birth is high.
      This study aimed to assess the prevalence and determinants of home birth among
      women who were booked for ANC in public hospitals in Wolaita zone, southern
      Ethiopia. METHODS: A cohort study was conducted from February to May 2017 among
      554 third trimester pregnant mothers who visited public hospitals of Wolaita
      Zone, southern Ethiopia for ANC service. All women were interviewed twice: the
      first interview was done face-to-face in the health facility in which they were
      having ANC follow up to gather information about basic socio-demographic and
      obstetric characteristics; the second interview was done via telephone after they
      gave birth to get information about the place of birth. Epi-Data version 3.1 was
      used for data entry and the Statistical Package for the Social Sciences (SPSS)
      version 22 was used for data analysis. RESULTS: A total of 68 (13.5%; 95%
      Confidence Interval (CI): 10.5%-16.6%) women who were booked for ANC gave birth
      at home. Being uneducated (AOR = 2.46, 95% CI: [1.10-5.10]), starting ANC visit
      late (>16weeks) (AOR = 2.27, 95% CI: [1.14-4.50]), time taken to reach at health
      facility for ANC service (>30minutes) (AOR = 8.94, 95% CI: [4.50-17.72]), waiting
      time of greater than 30 minutes for ANC in health facilities (AOR = 1.18, 95% CI:
      [1.06-2.30]) and lack of knowledge about danger signs of pregnancy (AOR = 4.18,
      95%CI: [1.80-9.70]) were significantly associated with home birth. CONCLUSIONS:
      Home birth among ANC booked women is low compared to other studies. Yet, giving
      attention to women with no education and those coming from far areas while
      providing advice on birth preparedness and pregnancy danger signs may be useful
      to further reduce the rate of home birth. Advising mothers to start ANC early and
      trying to reduce ANC waiting time could also be of importance.

PMID- 30192860
TI  - Nejire/dCBP-mediated histone H3 acetylation during spermatogenesis is essential
      for male fertility in Drosophila melanogaster.
AB  - Spermatogenesis in many species including Drosophila melanogaster is accompanied
      by major reorganisation of chromatin in post-meiotic stages, involving a nearly
      genome-wide displacement of histones by protamines, Mst77F and Protamine-like
      99C. A proposed prerequisite for the histone-to-protamine transition is massive
      histone H4 hyper-acetylation prior to the switch. Here, we investigated the
      pattern of histone H3 lysine acetylation and general lysine crotonylation in D.
      melanogaster spermiogenesis to elucidate a possible role of these marks in
      chromatin reorganisation. Lysine crotonylation was strongest prior to remodelling
      and the deposition of this mark depended on the acetylation status of the
      spermatid chromatin. In contrast to H4 acetylation, individual H3 acetylation
      marks displayed surprisingly distinct patterns during the histone-to-protamine
      transition. We observed that Nejire, a histone acetyl transferase, is expressed
      during the time of histone-to-protamine transition. Nejire knock down led to
      strongly reduced fertility, which correlated with misshaped spermatid nuclei and
      a lack of mature sperm. protA and prtl99C transcript levels were reduced after
      knocking down Nejire. ProtB-eGFP, Mst77F-eGFP and Prtl99C-eGFP were synthesized
      at the late canoe stage, while histones were often not detectable. However, in
      some cysts histones persist in parallel to protamines. Therefore, we hypothesize
      that complete histone removal requires multiple histone modifications besides
      H3K18ac and H3K27ac. In summary, H3K18 and H3K27 acetylation during Drosophila
      spermatogenesis is dependent on Nejire or a yet uncharacterized acetyl
      transferase. We show that Nejire is required for male fertility since Nejire
      contributes to efficient transcription of protA and prtl99C, but not Mst77F, in
      spermatocytes, and to maturation of sperm.

PMID- 30192867
TI  - Does the regional deprivation impact the spatial accessibility to dental care
      services?
AB  - The aim of the present study was to assess the regional deprivation and
      individual factors that influence how far a person will travel to access dental
      care. Using data from the Korea Health Panel (2008 to 2011), we selected a group
      of 4,256 subjects and geocoded their homes and dental hospitals/clinics. Using
      the road network analysis, we calculated the distance traveled by the subjects
      for dental care. We used the generalized estimating equation (GEE) for repeated
      data analysis and included an interaction term between regional deprivation and
      individual income to determine the effects of the two factors on the choice of a
      dental hospital/clinic. When the regional deprivation index was divided into
      three quarters (high, middle, and low), urban areas had higher"high" and "low"
      levels of deprivation, and rural areas had relatively higher middle level of
      deprivation. GEE regression showed that the level of education, regional
      deprivation level, and income all affected the distance traveled to dental
      clinics. The regional deprivation level had a higher association than income with
      the travel distance. At the same income level, subjects who lived in the least
      deprived areas were more likely to travel longer distances than subjects living
      in the most deprived areas. Regarding the distribution of dental
      hospitals/clinics, incentive based dental polices for either dental providers or
      patients are needed that will assure the delivery of dental care despite spatial
      inequality.

PMID- 30192866
TI  - Normative 3D opto-electronic stereo-photogrammetric sagittal alignment parameters
      in a young healthy adult population.
AB  - This paper describes and presents a stable and reliable set of stereo
      photogrammetric normative data for global and spino-pelvic sagittal alignment, as
      a proven reference system for evaluating/measuring a fully unconstrained natural
      upright neutral standing attitude in a young healthy adult population. The
      methodological features described in this article will enable future studies to
      replicate and/or directly compare a wide range of different postural tests and/or
      sagittal alignment assessment procedures including the study of sagittal spine
      shape variations occurring during gait performance. To date, the quantitative
      evaluation of adult spinal deformity (ASD) has been mainly confined to the X-ray
      imaging approach and, more recently, to 3D X-ray reconstruction. Within the
      existing evaluation framework an opportunity exists for an additional approach: a
      quantitative evaluation procedure which is easy, accurate, relatively speedy and
      non-ionising, in order to monitor and track the progress of patients in the areas
      of both surgical and non-surgical treatment. The resources and methodology
      described in this paper have been proven to meet all these criteria. They have
      enabled full 3D posture (including 3D spine shape and sagittal alignment of the
      skeleton) to be consistently and successfully measured in adult volunteers. All
      the measurement/evaluation procedures and outcomes carried out were based
      entirely on the new non-ionising 3D opto-electronic stereo-photogrammetric
      approach described in this article. The protocol for this methodology was based
      on a standard set of 27 pre-selected anatomical "landmarks" on the human body,
      providing standard reference points for observation and measurement. A total of
      124 healthy subjects were successfully assessed and, for each subject, 27
      individual markers were applied to the corresponding locations on his/her body.
      Statistical tests to investigate gender differences were also carried out.
      Descriptive statistics are provided for all 15 of the spino-pelvic parameters
      under consideration. Results indicated significant differences between genders in
      five sets of parameters: Kyphosis tilt, Head tilt, Pelvic tilt, Spino-pelvic
      angle and T1-pelvic angle. The data also demonstrate a high degree of congruity
      with results obtained using the X-ray method, as evidenced by the existing
      literature in the field. In summary, the current study presents a new stereo
      photogrammetric opto-electronic technology which can be used successfully for ASD
      evaluation and introduces a comprehensive set of normative data analogous to
      those proposed in X-ray analysis for sagittal spino-pelvic and total body
      alignment.

PMID- 30192865
TI  - Role of S1P/S1PR3 axis in release of CCL20 from human bronchial epithelial cells.
AB  - BACKGROUND: Sphingosine kinase phosphorylates sphingosine to generate sphingosine
      1 phosphate (S1P) following stimulation of the five plasma membrane G-protein
      coupled receptors. The objective of this study is to clarify the role of S1P and
      its receptors (S1PRs), especially S1PR3 in airway epithelial cells. METHODS: The
      effects of S1P on asthma-related genes expression were examined with the human
      bronchial epithelial cells BEAS-2B and Calu-3 using a transcriptome analysis and
      siRNA of S1PRs. To clarify the role of CCL20 in the airway inflammation, BALB/c
      mice were immunized with ovalbumin (OVA) and subsequently challenged with an OVA
      containing aerosol to induce asthma with or without intraperitoneal
      administration of anti-CCL20. Finally, the anti-inflammatory effect of VPC 23019,
      S1PR1/3 antagonist, in the OVA-induced asthma was examined. RESULTS: S1P induced
      the expression of some asthma-related genes, such as ADRB2, PTGER4, and CCL20, in
      the bronchial epithelial cells. The knock-down of SIPR3 suppressed the expression
      of S1P-inducing CCL20. Anti-CCL20 antibody significantly attenuated the
      eosinophil numbers in the bronchoalveolar lavage fluid (P<0.01). Upon OVA
      challenge, VPC23019 exhibited substantially attenuated eosinophilic inflammation.
      CONCLUSIONS: S1P/S1PR3 pathways have a role in release of proinflammatory
      cytokines from bronchial epithelial cells. Our results suggest that S1P/S1PR3 may
      be a possible candidate for the treatment of bronchial asthma.

PMID- 30192864
TI  - Energy balance-related parenting and child-care practices: The importance of meso
      system consistency.
AB  - BACKGROUND: Our knowledge of the role of parental and child-care staff behavior
      in the development and prevention of obesity is rapidly increasing. Potential
      interaction between both settings in so-called meso-systems, as hypothesized by
      the ecological systems perspective, is however often ignored. Specifically,
      inconsistency between home and child-care is hypothesized to have negative
      effects on child outcomes. METHODS: Participants were recruited through 23 child
      care centers in the Netherlands. Data regarding 161 child-parent-child-care staff
      triads were available. Parenting and child care practices were assessed using
      validated questionnaires for parents (Child Feeding Practices Questionnaire,
      Preschooler Physical Activity Parenting Practices instrument) and child-care
      staff (Child-care Food and Activity Practices Questionnaire), using similar items
      in both settings. Absolute difference scores between parents and child-care staff
      were calculated for each triad as a measure of meso-system consistency. Child
      outcomes were physical activity (as assessed by accelerometry), dietary intake
      (from the parental questionnaire), and measured BMI z-scores. Paired t-tests were
      used to examine consistency between practices in both settings. Linear regression
      analyses were used to explore the association of parenting practices, child-care
      practices and difference scores on the one hand, and child outcomes on the other.
      RESULTS: Significant differences between settings were found for almost all
      practices, and in most cases child-care staff scores more favorable on the
      practices than parents. Inconsistencies were mostly associated with unhealthy
      dietary intake and lower physical activity levels, but not with BMI. CONCLUSION:
      The current study showed that inconsistencies in parenting and child-care
      practices exist, and that these inconsistencies seem to be associated with
      unhealthy behavior in children. The results underline the importance of studying
      meso-system influences on behavior in general, and children's energy balance
      related behavior specifically.

PMID- 30192868
TI  - Systematic review of the effects of agricultural interventions on food security
      in northern Ghana.
AB  - BACKGROUND: Food insecurity and poverty rates in Ghana are highest in the
      districts from latitude 8 degrees  N upwards. These have motivated several
      interventions aimed at addressing the food insecurity via promoting agricultural
      growth. An assessment of the overall impact of these interventions on food
      security is necessary to guide policy design and future interventions. METHODS
      AND FINDINGS: A systematic review was used to assess the cumulative evidence of
      the effect of development interventions, implemented from 2006 to 2016 on food
      security, especially in Northern Ghana. Information were retrieved from over 20
      Government and non-Governmental organisations through online search and actual
      visits. The number of studies included in systematic review was 22. The study
      showed that a large number of interventions have been implemented in Northern
      Ghana over the study period. Access to quality extension services, training and
      capacity building was a major intervention strategy. About 82% of studies
      considered increasing production but only 14% of the studies reported on changes
      in yield. About 42% of the included studies used market access as a strategy but
      about 44% reported increase in incomes of beneficiaries (with only seven studies
      providing numerical evidence for this claim). The ranking of frequency of
      intervention strategies was in the order extension and capacity building >
      production > postharvest value addition > water and irrigation facilities >
      storage facilities > input supply. A substantial number of the studies had no
      counterfactuals, weakening confidence in attributing impacts on food security for
      even the beneficiaries. CONCLUSIONS: It is concluded that evidence for impacts of
      the interventions on food security was weak, or largely assumed. A logical
      recommendation is the need for development partners to synchronise their
      measurement and indicators of food security outcomes. It is also recommended that
      some food security indicators are explicitly incorporated into intervention
      design while bearing in mind the potential need for counterfactuals.

PMID- 30192869
TI  - Rotavirus VP6 protein mucosally delivered by cell wall-derived particles from
      Lactococcus lactis induces protection against infection in a murine model.
AB  - Rotaviruses are the primary cause of acute gastroenteritis in children worldwide.
      Although the implementation of live attenuated vaccines has reduced the number of
      rotavirus-associated deaths, variance in their effectiveness has been reported in
      different countries. This fact, among other concerns, leads to continuous efforts
      for the development of new generation of vaccines against rotavirus.In this work,
      we describe the obtention of cell wall-derived particles from a recombinant
      Lactococcus lactis expressing a cell wall-anchored version of the rotavirus VP6
      protein. After confirming by SDS-PAGE, Western blot, flow cytometry and
      electronic immunomicroscopy that these particles were carrying the VP6 protein,
      their immunogenic potential was evaluated in adult BALB/c mice. For that, mucosal
      immunizations (oral or intranasal), with or without the dmLT [(double mutant
      Escherichia coli heat labile toxin LT(R192G/L211A)] adjuvant were performed. The
      results showed that these cell wall-derived particles were able to generate anti
      rotavirus IgG and IgA antibodies only when administered intranasally, whether the
      adjuvant was present or not. However, the presence of dmLT was necessary to
      confer protection against rotavirus infection, which was evidenced by a 79.5
      percent viral shedding reduction.In summary, this work describes the production
      of cell wall-derived particles which were able to induce a protective immune
      response after intranasal immunization. Further studies are needed to
      characterize the immune response elicited by these particles as well as to
      determine their potential as an alternative to the use of live L. lactis for
      mucosal antigen delivery.

PMID- 30192870
TI  - The influence of acute kidney injury on the outcome of Stevens-Johnson syndrome
      and toxic epidermal necrolysis: The prognostic value of KDIGO staging.
AB  - BACKGROUND: Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and
      SJS/TEN overlap syndrome are severe drug-induced cutaneous adverse reactions with
      high mortality. Acute kidney injury (AKI) was a common complication in an SJS/TEN
      group and noted as an independent risk factor for mortality in patients with
      SJS/TEN. To determine whether AKI staging can predict the outcome of patients
      with SJS/TEN, we compared the discriminative power of an AKI KDIGO staging system
      with that of SCROTEN, APACHE II, APACHE III, and SOFA. MATERIALS AND METHODS: We
      retrospectively analyzed the data of 75 patients who were diagnosed with SJS,
      TEN, or SJS/TEN overlap syndrome at a tertiary care university hospital between
      January 1, 2011 and December 31, 2014. The baseline characteristics, biochemical
      analysis data, medication use, and outcomes of the patients were assessed, and
      the discriminative ability for predicting mortality was determined for each
      prognostic model. RESULTS: Of the 75 patients, 23 (30.7%) had AKI, of whom 13
      (56.5%) died during the index admission. Of the prognostic risk models analyzed,
      the KDIGO staging system showed similar discriminative ability in predicting in
      hospital mortality as did the other models. In addition, combining KDIGO with
      other scoring systems yielded significantly more accurate risk prediction for in
      hospital mortality compared with the other individual scores alone, as measured
      by net reclassification index. The patients with KDIGO stages 2 and 3 exhibited a
      significantly lower 1-year survival rate than did those with KDIGO stages 0 and
      1. CONCLUSION: AKI KDIGO staging has good discriminative ability and is easy to
      utilize for predicting mortality.

PMID- 30192871
TI  - Impaired hepatic amyloid-beta degradation in Alzheimer's disease.
AB  - Extensive research strongly suggests that amyloid beta (Abeta) aggregates in the
      brain have a central role in Alzheimer's disease (AD) pathogenesis. Pathological
      Abeta deposition is likely due to an altered balance between overproduction and
      elimination. Rodent studies have suggested that the liver has a major role in
      Abeta degradation. It is possible alterations of liver function could affect
      brain Abeta levels through changes in blood Abeta concentration. In this study,
      we hypothesized hepatic Abeta degradation to be impaired in AD subjects. To test
      our hypothesis, an Abeta degradation assay was developed using synthetic
      fluorescein-labeled Abeta40 and Abeta42 spiked into human liver homogenates.
      Abeta degradation rates were lower in AD-derived homogenates as compared with
      those from non-demented (ND) control subjects, even after accounting for such
      covariates as age, sex, and APOE genotype. The protein expression of potential
      Abeta-degrading enzymes were also examined. Neprilysin levels were not different
      in AD liver samples, while cathepsin D and insulin-degrading enzyme were
      significantly altered in AD subjects. The results support the possibility that
      impaired hepatic Abeta degradation could be a factor contributing to increased
      brain Abeta accumulation and AD.

PMID- 30192872
TI  - Parents' depression and loneliness during pregnancy and respiratory infections in
      the offspring: A prospective birth cohort study.
AB  - BACKGROUND: An association between maternal prenatal stress and increased rates
      of respiratory tract infections in the offspring has been described earlier. Data
      regarding the father's role is lacking. In this study our aim was to evaluate,
      whether mothers' and fathers' depressive symptoms and loneliness during pregnancy
      predict higher rates of respiratory tract infections in the offspring. METHODS:
      In this longitudinal cohort study we gathered information on parental
      psychological risk during gestational week 20 using the BDI-II and UCLA
      loneliness scale questionnaires for the parents of 929 children. Loneliness was
      divided into social and emotional components, the former describing patterns of
      social isolation and the latter a perceived lack of intimate attachments.
      Episodes of acute otitis media, physician visits due to respiratory tract
      infections, and antibiotic consumption relating to respiratory tract infections
      were documented in the infants, excluding twins, from birth until 10 months of
      age using study diaries. Analyses were carried out by structural equation
      modeling, which provides dynamic estimates of covariances. RESULTS: Maternal
      depressive symptoms during pregnancy predicted higher rates of acute otitis media
      in the infant and maternal emotional loneliness predicted higher rates of
      physician visits. Acute otitis media, physician visits and antibiotic consumption
      in the infant were slightly less frequent for families who reported social
      loneliness in the father or mother. Associations remained when taking into
      account confounders. CONCLUSIONS: Maternal prenatal depression and emotional
      loneliness predicted a higher burden of respiratory tract infections in the
      offspring. The protective influence of parental social loneliness on the burden
      of respiratory tract infections in infants was not in line with our study
      hypothesis, but could be explained by reduced use of healthcare services in these
      socially isolated families.

PMID- 30192873
TI  - Nepalese migrants in Japan: What is holding them back in getting access to
      healthcare?
AB  - INTRODUCTION: Migrants are one of the most deprived and vulnerable groups who
      receive the least health services in the society. Only a few studies have been
      conducted on access to healthcare among migrants in Asia, despite hosting 75
      million migrants. In Japan, Nepalese migrants constitute the largest South Asian
      community. Their number increased by three folds from 2011 to 2016. However,
      little is known about their access to health care in Japan. Based on Andersen's
      model, we examined the factors associated with access to healthcare among
      Nepalese migrants in Japan. METHODS: We conducted a cross-sectional study among
      642 Nepalese migrants residing in 10 prefectures of Japan. We used multivariable
      logistic regression model to explore the key predisposing, enabling, and need
      factors associated with access to healthcare among the migrants. RESULTS: The
      migrants who had stayed in Japan longer were more likely to perceive better
      access to a doctor/health worker (AOR = 1.11, 95% CI 1.03-1.19).The migrants were
      more likely to perceive better access to a doctor/health worker (AOR = 1.79, 95%
      CI 1.17-2.73) when they did not need Japanese language interpreter during visit
      to health facilities. They were also less likely not to see a doctor/health
      worker when needed (AOR = 0.34, 95% CI 0.21-0.56). The migrants were less likely
      to perceive better access to a doctor/health worker when they had not paid the
      health insurance premium regularly (AOR = 0.21, 95% CI 0.13-0.33).Their low
      perception of better access to a doctor/health worker was also associated with
      self-rated health status as poor or fair (AOR = 0.60, 95% CI 0.41-0.89).
      CONCLUSION: Nepalese migrants have poor access to health care in Japan. The key
      factors associated with their access to health care are the length of stay
      (predisposing factor), Japanese language skill and health insurance (enabling
      factors) and self-rated health status (need factor).

PMID- 30192875
TI  - Effect of intergenerational educational mobility on health of Indian women.
AB  - This study aims to analyse the relationship between intergenerational educational
      mobility and the overall health of the Indian women. It uses a nationally
      representative survey, India Human Development Survey (IHDS) 2011-12, and
      logistic regressions to study this relationship. The sample comprises of women
      aged 45 years and older. We find that the women experiencing upward
      intergenerational educational mobility (vis-a-vis their mothers) have
      significantly higher chances of experiencing good overall health compared to the
      women who are having same or lesser level of education as that of their mothers.
      Besides, women suffering from short term or major morbidity have remarkably lower
      chances of having overall good health. Also, women from rural India have
      significantly lesser chances of having overall good health as compared to that of
      urban areas. Further, Muslim women have lesser chances of having overall good
      health as that of women from other religious categories. Moreover, there is a
      significant variation in the overall health of women as we move from the eastern
      region to the western region of India.

PMID- 30192874
TI  - Cariogenic potential of sweet flavors in electronic-cigarette liquids.
AB  - BACKGROUND: Most electronic-cigarette liquids contain propylene glycol, glycerin,
      nicotine and a wide variety of flavors of which many are sweet. Sweet flavors are
      classified as saccharides, esters, acids or aldehydes. This study investigates
      changes in cariogenic potential when tooth surfaces are exposed to e-cigarette
      aerosols generated from well-characterized reference e-liquids with sweet
      flavors. METHODS: Reference e-liquids were prepared by combining 20/80 propylene
      glycol/glycerin (by volume fraction), 10 mg/mL nicotine, and flavors. Aerosols
      were generated by a Universal Electronic-Cigarette Testing Device (49.2 W, 0.2
      Omega). Streptococcus mutans (UA159) were exposed to aerosols on tooth enamel and
      the biological and physiochemical parameters were measured. RESULTS: E-cigarette
      aerosols produced four-fold increase in microbial adhesion to enamel. Exposure to
      flavored aerosols led to two-fold increase in biofilm formation and up to a 27%
      decrease in enamel hardness compared to unflavored controls. Esters (ethyl
      butyrate, hexyl acetate, and triacetin) in e-liquids were associated with
      consistent bacteria-initiated enamel demineralization, whereas sugar alcohol
      (ethyl maltol) inhibited S. mutans growth and adhesion. The viscosity of the e
      liquid allowed S. mutans to adhere to pits and fissures. Aerosols contained five
      metals (mean +/- standard deviation): calcium (0.409 +/- 0.002) mg/L, copper
      (0.011 +/- 0.001) mg/L, iron (0.0051 +/- 0.0003) mg/L, magnesium (0.017 +/-
      0.002) mg/L, and silicon (0.166 +/- 0.005) mg/L. CONCLUSIONS: This study
      systematically evaluated e-cigarette aerosols and found that the aerosols have
      similar physio-chemical properties as high-sucrose, gelatinous candies and acidic
      drinks. Our data suggest that the combination of the viscosity of e-liquids and
      some classes of chemicals in sweet flavors may increase the risk of cariogenic
      potential. Clinical investigation is warranted to confirm the data shown here.

PMID- 30192876
TI  - Differential impact of circulating tumor cells on disease recurrence and
      survivals in patients with head and neck squamous cell carcinomas: An updated
      meta-analysis.
AB  - PURPOSE: The prognostic impact of circulating tumor cells (CTC) on disease
      recurrence, progression and survivals in patients with head and neck squamous
      cell carcinoma (HNSCC) has not been adequately described. The objective of this
      study was to determine the impacts of the presence of CTC on loco-regional
      recurrence and survival of HNSCC patients by conducting a systematic review and
      meta-analysis. METHODS: A comprehensive search for articles published between
      1990 and 2016 was conducted and data from these studies were extracted, using the
      MEDLINE, Cochrane Library, and EMBASE databases. The main outcomes were overall
      survival (OS) and recurrence-free survival (RFS) of HNSCC patients. Pooled hazard
      ratio (HR) and 95% confidence intervals (95%CI) were calculated using the random
      effect model for outcomes. The quality of the studies, heterogeneity and
      publication bias were assessed with the appropriate statistical methods. RESULTS:
      Six eligible studies with 429 patients were identified. The presence of CTC was
      significantly associated shorter RFS (HR = 4.88 [95%CI: 1.93-12.35], P < 0.001).
      However, it could not predict patients' OS (HR = 1.92 [95%CI: 0.93-3.96], P =
      0.078). The following analyses using univariable values of each study also made
      the similar results (HR = 1.70 [95%CI: 0.83-3.45] for OS, HR = 3.79 [95%CI: 2.02
      7.13] for RFS). Heterogeneity and publication bias were not significant, except
      one enrolled study. CONCLUSIONS: The presence of CTC is not a significant
      prognostic indicator for OS of patients with HNSCC, although it could reflect the
      outcomes of loco-regional disease.

PMID- 30192877
TI  - Chitosan biopolymer promotes yield and stimulates accumulation of antioxidants in
      strawberry fruit.
AB  - Strawberry is a well-known source of natural antioxidants with excellent free
      radical scavenging capacity. This study determined the effects of chitosan
      application in field condition on plant growth, fruit yield and antioxidant
      activities in strawberry fruit. Foliar applications of chitosan on strawberry
      significantly increased plant growth and fruit yield (up to 42% higher) compared
      to untreated control. Increased fruit yield was attributed to higher plant
      growth, individual fruit weight and total fruit weight/plant due to the chitosan
      application. Surprisingly, the fruit from plants sprayed with chitosan also had
      significantly higher contents (up to 2.6-fold) of carotenoids, anthocyanins,
      flavonoids and phenolics compared to untreated control. Total antioxidant
      activities in fruit of chitosan treated plants were also significantly higher
      (ca. 2-fold) (p< 0.05) than untreated control. To the best of our knowledge, this
      is the first report of chitosan applied on field plants providing significant
      improvement of both yield and health benefiting biochemical contents in
      strawberry fruit. Further study on the elucidation of mechanisms involved with
      enhancement of growth, yield and biochemical contents by chitosan is needed to
      promote sustainable production of strawberry.

PMID- 30192878
TI  - Mean platelet volume and lymphocyte-to-monocyte ratio are associated with shorter
      progression-free survival in EGFR-mutant lung adenocarcinoma treated by EGFR
      tyrosine kinase inhibitor.
AB  - BACKGROUND: A growing body of evidence supports the role of platelets in cancer
      metastasis, escape from immune surveillance, and angiogenesis. Mean platelet
      volume (MPV), which reflects platelet turnover, is reported routinely as part of
      automated complete blood count. Accumulating evidence suggests that MPV is a
      useful biomarker in several diseases including cancer. However, its role in
      cancer patients receiving molecular targeted therapy has not been described in
      the literature. MATERIALS AND METHODS: We retrospectively analysed the prognostic
      impact of MPV in advanced or recurrent EGFR mutant lung adenocarcinoma treated
      with EGFR tyrosine kinase inhibitors (EGFR-TKIs). Lymphocyte-to-monocyte ratio
      (LMR) has been previously reported to be a poor prognostic factor in EGFR mutant
      non-small cell lung cancer and was also included as a covariate. RESULTS: Using
      the previously described Cutoff Finder algorithm, the cut-off points for MPV and
      LMR that best predicted progression free survival (PFS) of EGFR-TKI were
      determined as 10.3 and 2.8, respectively. The median PFS was 14.7 and 8.2 months
      in MPV low and high groups (p = 0.013, log-rank test). The median PFS was 13.5
      and 6.2 months in LMR high and low groups (p < 0.001, log-rank test). MPV and LMR
      were independently distributed (chi square test) and the multivariate analysis
      using Cox's proportional hazards regression model revealed that high MPV, low
      LMR, and pleural effusion were significant predictors for shorter PFS.
      CONCLUSION: MPV and LMR, measured as part of routine complete blood count, can be
      utilized to predict the outcome of EGFR-TKI therapy with no additional costs. Our
      results suggest a mechanism of EGFR-TKI resistance which is associated with the
      functional status of the platelets.

PMID- 30192879
TI  - Bioimaging of alloantigen-stimulated regulatory T cells in rat vascularized
      composite allotransplantation.
AB  - BACKGROUND: Tipping the balance toward regulatory T cells (Tregs) through
      adoptive cell therapy has shown promise to induce transplantation tolerance.
      Although such strategy has been explored in many mice organ transplantation
      studies, less knowledge was available in rat systems. Furthermore, the behaviors
      of the transferred cells have not been well studied in real-time fashion.
      METHODS: Tregs from naive LEW rats were purified in two steps with the autoMACS
      system. Immunosuppression potential of these cells was examined with mixed
      lymphocyte reaction. Following stimulation by the alloantigen in vitro, the
      purified Tregs were infused into the recipients of vascularized composite
      allotransplantation (VCA). Secondary allogeneic skin grafting challenge was
      performed on the recipients with long-term survived VCA. Live optical imaging was
      performed to track luciferase-expressing Tregs following infusion to the VCA
      recipients. Expression of relevant molecules was studied by flow cytometry or
      quantitative RT-PCR. RESULTS: Rat Tregs were enriched following two-step cell
      sorting and showed immunosuppressive capacity. Upon infusion into the VCA
      recipients that have been treated with antilymphocyte serum and short-term
      Cyclosporin A, the antigen-stimulated Tregs significantly prolonged VCA survival
      and induced donor-specific tolerance. Tracking of the infused bioluminescent
      Tregs showed their specific homing to lymph nodes, and then to the VCAs.
      Following secondary skin grafting, Tregs specifically gathered at the donor
      derived skin that was not rejected by the recipient. The in vivo migratory
      pattern coincided with the altered expression of cell surface molecules of CD62L,
      CD103, CD134, and CD278, following donor-antigen stimulation. Elevated expression
      of CCR4 and CCL22 in allograft may also participate in recruiting Tregs for
      maintenance of VCA survival and promoting donor-specific tolerance. CONCLUSION:
      Sorted Tregs induced donor-specific tolerance to VCA in rats. Live cell tracking
      demonstrated that activated CD4+CD25+FoxP3+ Tregs targeted primarily to the lymph
      nodes and VCA. The Tregs migrated to the secondary grafted donor skin and
      contributed to the maintenance of donor-specific tolerance. These behaviors were
      associated with phenotypic changes induced by donor antigen stimulation.
      Increased expression of CCR4 and CCL22 in VCA skin may also be relevant.

PMID- 30192881
TI  - Long-term effect of soil and water conservation measures on runoff, sediment and
      their relationship in an orchard on sloping red soil of southern China.
AB  - The effect of soil and water conservation measures (SWCMs) is usually dependent
      on time. Thus the trend in reducing runoff and sediment over time is a very
      important theoretical problem for evaluating the effectiveness of SWCMs.
      Moreover, there is still a lack of comprehensive assessment of water erosion
      dynamics following implementing SWCMs despite their ecological significance.
      Therefore, the long-term impact of SWCMs on runoff and sediment and their
      relationships was assessed for an orchard on sloping red soil in southern China.
      Overland flow and erosion sediment were continuously observed for 15 years on
      citrus experimental plots under one of four treatments: grass strips, strip
      intercropping, level terrace and clean-tillage. By means of Mann-Kendall trend
      tests and double cumulative curves, the time series of runoff and sediment under
      the different treatments were analyzed. Furthermore, we linked the effect of soil
      conservation and the relationship between runoff and sediment variation to
      determine the mechanism of conservation measures on sediment reduction. The
      results showed that the first 4 years was the key period to prevent soil erosion
      for this orchard, and then the intensity of soil erosion decreased below 500 t.km
      2.a-1. Considering economic costs and ecological effect, grass strips were the
      best protective measure for this test situation. The fitted curves of the effect
      of SWCMs on sediment reduction over time showed an 'L' form, but on runoff there
      was an approximately horizontal line. The SWCMs did not change the rainfall
      runoff relationship, but did change the runoff-sediment erosion relationship. The
      erosion reduction mechanism of SWCMs in the early phase was a joint function of
      reducing runoff and changing the runoff-sediment relationship, and in the post
      stable phase it worked mainly by reducing runoff. The results provide the basis
      for rational allocation of SWCMs considering location and time.

PMID- 30192880
TI  - Under-five mortality in the Rongo Sub-County of Migori County, Kenya: Experience
      of the Lwala Community Alliance 2007-2017 with evidence from a cross-sectional
      survey.
AB  - INTRODUCTION: Childhood mortality remains a pressing problem in rural Kenya, and
      reducing under-five deaths is a key target of the Sustainable Development Goals.
      We aim to describe the reduction in under-five mortality in a rural Kenyan
      community served by the Lwala Community Alliance and factors associated with
      under-five mortality in this community. METHODS: A cross-sectional survey
      containing a complete birth history was administered to a representative sample
      of the catchment area of the Lwala Community Alliance. Survival analysis
      techniques were used to describe temporal trends and risk factors related to
      under-five mortality. RESULTS: 1,362 children were included in the study, and 91
      children died before the fifth birthday. The most common causes of death among
      children under five were malaria (19%), respiratory infection (13%), and anemia
      (11%). The under-five mortality rate was 104.8 per 1,000 live births from 1999 to
      2006 and 53.0 per 1,000 after the founding of the Lwala Community Alliance in
      2007. Factors associated with under-five mortality included year of birth (HR
      0.931; 95% CI: 0.877, 0.988; p = 0.019), multiple-gestation pregnancy (HR 6.201;
      95% CI: 2.073, 18.555; p < 0.001), and birth in the long rain season (HR 1.981;
      95% CI: 1.350, 2.907; p < 0.001). Birth spacing greater than 18 months was
      negatively associated with under-five mortality (HR 0.345; 95% CI: 0.203, 0.587;
      p < 0.001). CONCLUSIONS: There was a significant decrease in under-five mortality
      before and after the presence of the Lwala Community Alliance. Multiple-gestation
      pregnancies, birth season, and short birth spacing were associated with under
      five mortality and provide possible targets to further reduce mortality in the
      region. This provides both hyper-local data necessary for implementation efforts
      and generalizable data and sampling methods that may be useful for other
      implementing organizations in sub-Saharan Africa.

PMID- 30192882
TI  - Navigating the path to a biomedical science career.
AB  - The number of biomedical PhD scientists undergoing training and graduating far
      exceeds the number of academic faculty positions and academic research jobs. This
      trend compels biomedical PhD scientists to increasingly seek career paths outside
      of academia. Prior studies have used quantitative methodology to determine trends
      and outcomes of single factors contributing to this shift, but there is a
      literature gap in studies considering multiple factors and in qualitative work
      focusing on biomedical PhD scientists' experiences and their processes of career
      navigation. This paper draws on a social cognitive career theory (SCCT) framework
      and incorporates case study data from a southeastern Tier 1 research university
      to explore a nexus of factors influencing PhD scientists' employment sector
      preferences and job search processes. It simultaneously concludes that
      relationships with faculty, particularly the mentor advisor, are essential to the
      opportunities available to these professionals and to the career paths they
      choose.

PMID- 30192883
TI  - Gastric corticotropin-releasing factor influences mast cell infiltration in a rat
      model of functional dyspepsia.
AB  - Functional gastrointestinal disorders (FGIDs) are characterized by dysregulated
      gut-brain interactions. Emerging evidence shows that low-grade mucosal
      inflammation and immune activation contribute to FGIDs, including functional
      dyspepsia (FD). Stress plays an important role in the onset of FD symptoms. In
      human subjects with FD, presence of gastric mast cells has been reported, but
      factors that influence mast cell infiltration remain uncharacterized.
      Corticotropin-releasing factor (CRF) initiates the body's stress response and is
      known to degranulate mast cells. In this study, we delineated the role of the CRF
      system in the pathogenesis of FD in a rat model. Gastric irritation in neonate
      rat pups with iodoacetamide (IA) was used to induce FD-like symptoms. RNA
      interference (RNAi) was used to silence gastric CRF expression. Mast cell
      infiltrate in the stomach increased by 54% in IA-treated rats compared to
      controls and CRF-RNAi tended to decrease gastric mast cell infiltrate. Sucrose
      intake decreased in IA-treated rats and mast cell numbers showed a negative
      association with sucrose intake. IA treatment and transient silencing of gastric
      CRF increased hypothalamic CRF levels. In IA-treated rats, gastric levels of CRF
      receptor 2 (CRF2) decreased by ~76%, whereas hypothalamic CRF receptor 1 (CRF1)
      levels increased. Plasma levels of TNF-alpha showed a positive correlation with
      plasma CRF levels. Levels of phosphorylated p38 and ERK1/2 in the stomach showed
      a positive correlation with gastric CRF levels. Thus, CRF may contribute to low
      grade inflammation via modulating mast cell infiltration, cytokine levels, MAPK
      signaling, and the gut-brain axis.

PMID- 30192885
TI  - Dairy products viscosity estimated by laser speckle correlation.
AB  - Dairy products exhibit several physical properties that are crucial to define
      whether we like the food or not: firmness, creaminess, thickness, or lightness.
      Viscosity changes the flow properties of food and influences the appearance and
      the consistency of a product; this control variable is important in most
      production stages-manufacture, processing, and storage. Viscosity of
      heterogeneous products at a given temperature depends on its composition and
      physical state of its substances. Although rheology provides a method to access
      the product viscosity, it lacks non-contact full-field monitoring. We apply a
      simple correlation analysis of laser speckle images to evaluate viscosity
      properties of dairy products. Our approach ensures robust measurements with high
      degree of detectability.

PMID- 30192884
TI  - Determinants of birth asphyxia among live birth newborns in University of Gondar
      referral hospital, northwest Ethiopia: A case-control study.
AB  - BACKGROUND: Birth asphyxia, which accounts for 31.6% of all neonatal deaths, is
      one of the leading causes of such mortality in Ethiopia. Early recognition and
      management of its contributing factors would modify the problem. Thus, this study
      aimed to identify the determinants of birth asphyxia among live births at the
      University of Gondar Referral Hospital, northwest Ethiopia. METHODS: A hospital
      based unmatched case-control study was conducted from April to July 2017.Cases
      were newborn babies with an APGAR score of < 7at 5 minutes of birth; controls
      were newborn babies with an APGAR score of >=7 at 5 minutes of birth. Every other
      asphyxiated baby was selected as a case and every 6th non-asphyxiated baby as a
      control. A pretested structured questionnaire was used to collect data on
      maternal sociodemographic characteristics. A pretested structured checklist was
      used to retrieve data on ante-partum, intra-partum, and neonatal factors of both
      cases and controls. Data were entered using Epi Info 7 and analyzed using SPSS
      20. The bivariate logistic regression analysis was used to identify the relation
      of each independent variable to the outcome variable. Variables with p values of
      up to 0.2 in the bivariate analysis were considered for the multiple logistic
      regression analysis. An adjusted odds ratio (AOR) with a 95% CI and p-value of
      <0.05 was used to identify significant variables associated with birth asphyxia.
      RESULTS: In this study, prolonged labor (AOR = 2.75, 95% CI: 1.18, 6.94),
      cesarean section delivery (AOR = 3.58, 95% CI: 1.13, 11.31), meconium stained
      amniotic fluid (AOR = 7.69, 95% CI: 2.99, 17.70), fetal distress (AOR = 5.74, 95%
      CI: 1.53, 21.55), and low birth weight (AOR = 7.72, 95% CI: 1.88, 31.68) were
      factors which significantly increased the odds of birth asphyxia. CONCLUSION:
      Prolonged labor, cesarean section (CS) delivery, meconium stained amniotic fluid
      (AF), fetal distress, and low birth weight were the determinants of birth
      asphyxia. Thus, efforts should be made to improve the quality of intra-partum
      care services in order to prevent prolonged labor and fetal complications, and to
      identify and make a strict follow up on mothers with meconium stained amniotic
      fluid.

PMID- 30192886
TI  - Correction: Growth of the hard palate in infants with Down syndrome compared with
      healthy infants-A retrospective case control study.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0182728.].

PMID- 30192888
TI  - Correction: Communication Tools for End-of-Life Decision-Making in Ambulatory
      Care Settings: A Systematic Review and Meta-Analysis.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0150671.].

PMID- 30192887
TI  - Screening for hepatitis D and PEG-Interferon over Tenofovir enhance general
      hepatitis control efforts in Brazil.
AB  - BACKGROUND: Hepatitis D virus (HDV), which requires the presence of hepatitis B
      virus (HBV), is a deadly yet neglected disease that rapidly leads to liver cancer
      and disease-induced mortality. This co-dependence creates complex transmission
      dynamics that make it difficult to predict the efficacy of interventions aimed at
      HBV and/or HDV control in endemic regions, such as certain municipalities of
      Brazil, where up to 65% of HBV-infected persons are co-infected. METHODOLOGY: We
      created a mathematical model that captures the joint transmission dynamics of HBV
      and HDV, incorporating mother-to-child, sexual and household transmission. With
      an aim to minimize the number of total infections and disease-induced mortality
      in 2027, we then determined optimal strategies for Brazil and its sub-regions
      under a constrained budget, which was dynamically allocated among HBV and HDV
      screening, HBV and HDV treatment, HBV newborn and adult vaccination, and
      awareness programs. Three treatment options were considered, namely: Tenofovir,
      PEGylated-Interferon, and nucleic acid polymers (NAP). RESULTS: The additional
      cost of HDV screening and the use of a more expensive PEGylated-Interferon are
      offset by not wasting resources on treating co-infected persons with Tenofovir.
      The introductory price of NAP treatment must be less than $16,000 per course to
      become competitive with Tenofovir and PEGylated-Interferon in Brazil. CONCLUSION:
      Additional screening for HDV is beneficial, even in a low HBV and HDV endemic
      regions of Brazil. We recommend PEGylated-Interferon, wherever possible, for both
      HBV and HDV. If PEGylated-Interferon is not available in abundance, PEGylated
      Interferon for co-infections and 4-year Tenofovir treatment for mono-infections
      is recommended.

PMID- 30192889
TI  - Correction: Four-dimensional analysis by high-speed holographic imaging reveals a
      chiral memory of sperm flagella.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0199678.].

PMID- 30192890
TI  - Chinese herbal medicine reduced the risk of stroke in patients with Parkinson's
      disease: A population-based retrospective cohort study from Taiwan.
AB  - Parkinson's disease (PD) is associated with a significantly increased risk of
      stroke. Traditional Chinese medicine (TCM) has long been used in Asia to treat
      stroke, but there are no large-scale clinical data to confirm its efficacy in
      protecting PD patients against stroke. Herein, we analyzed a cohort of 1,000,000
      records from Taiwan's National Health Insurance Research Database for the period
      1997-2011, and identified 1,882 patients with new-onset PD. We matched 290
      patients who received Chinese herbal medicine (CHM) by age, sex, year of CHM
      prescription, and year of PD diagnosis with 290 patients who did not use CHM as
      control. Both cohorts were followed until the end of 2013 for the incidence of
      new-onset stroke. In a multivariable Cox proportional hazard model adjusted for
      potential comorbidities, the incidence of stroke was lower among PD patients
      using CHM compared with non-CHM users (11.10 per 100 person-years vs 23.15 per
      100 person-years; Hazard ratio: 0.56; 95% confidence interval:  0.44 to 0.72).
      The probability curve generated from our follow-up data showed that PD patients
      receiving CHM treatment had a decreased risk of stroke compared with those not
      receiving CHM treatment (P <0.001). The analysis on the prescription pattern of
      CHM revealed that Danshen is the most common single herb and Ma Zi Ren Wan is the
      most common herbal formula. Although the analysis are limited by a lack of
      analytic information regarding lifestyle patterns, biochemical profiles, and
      levels of PD severity in database, this population-based study suggest that CHM
      may be an complementary therapy to reduce the risk of stroke in PD patients.

PMID- 30192892
TI  - Effect of antiretroviral therapy on all-cause mortality among people living with
      HIV/AIDS in Ghana using Mahalanobis distant metric matching within propensity
      score caliper analysis: A retrospective cohort study.
AB  - Several health interventions have been put in place to improve health outcomes of
      people living with HIV/AIDS (PLHIV) in Ghana. We evaluated the impact of
      Antiretroviral Therapy (ART) on all-cause mortality in Ghana using matching
      procedures. This was a retrospective cohort study of 12,881 HIV/AIDS patients
      initiated on ART at 40 sentinel sites and 199 treatment centers between 2013 and
      2016 countrywide. Patients were included if they had date of ART initiation and
      if they had mortality outcome recorded. Mahalanobis distant metric matching
      within propensity score caliper and other matching procedures were used to
      evaluate the effectiveness of ART in reducing the risk of all-cause mortality
      among PLHIV in Ghana. We performed sensitivity analysis using different matching
      procedures including Kernel weighting adjustment and Mahalanobis distance metric
      matching with nearest neighbour to ascertain the robustness of our results in the
      presence of unmeasured covariates. The proportion of patients on ART was 60.3%
      (95% CI: 59.5-61.1). The total number of mortalities reported was only 734
      representing 4.6% (95% CI: 4.2-4.9) of the studied population. The risk of all
      cause mortality has reduced by 11.6 percentage point among HIV/AIDS patients who
      were on ART compared to those who were not on ART (95% CI: 9.6-13.4). ART was
      associated with a decreased risk of all-cause mortality. Effort being made by
      Government and non-Governmental organizations in support of ART treatment in
      Ghana should continue unabated to help reduce mortality rate and improve health
      outcomes among HIV/AIDS. To reduce bias to the barest minimum between treatment
      and intervention group when evaluating the effectiveness of health interventions,
      it is recommended to use matching procedures especially when the study design is
      not a randomized control trial.

PMID- 30192891
TI  - Role of simple descriptors and applicability domain in predicting change in
      protein thermostability.
AB  - The melting temperature (Tm) of a protein is the temperature at which half of the
      protein population is in a folded state. Therefore, Tm is a measure of the
      thermostability of a protein. Increasing the Tm of a protein is a critical goal
      in biotechnology and biomedicine. However, predicting the change in melting
      temperature (dTm) due to mutations at a single residue is difficult because it
      depends on an intricate balance of forces. Existing methods for predicting dTm
      have had similar levels of success using generally complex models. We find that
      training a machine learning model with a simple set of easy to calculate
      physicochemical descriptors describing the local environment of the mutation
      performed as well as more complicated machine learning models and is 2-6 orders
      of magnitude faster. Importantly, unlike in most previous publications, we
      perform a blind prospective test on our simple model by designing 96 variants of
      a protein not in the training set. Results from retrospective and prospective
      predictions reveal the limited applicability domain of each model. This study
      highlights the current deficiencies in the available dTm dataset and is a call to
      the community to systematically design a larger and more diverse experimental
      dataset of mutants to prospectively predict dTm with greater certainty.

PMID- 30192893
TI  - Understanding physician antibiotic prescribing behavior for children with
      enterovirus infection.
AB  - BACKGROUND: Our previous study demonstrated that pediatricians prescribe
      antibiotics without proper clinical justification to patients with enterovirus
      infection, although antibiotics are not effective in treating the infections
      caused by these viruses. To improve the quality of healthcare, we aim to evaluate
      the association of clinical and demographic characteristics of patients and
      further to identify the determining factors for prescribing antibiotics to
      children experiencing enterovirus infection. METHODS: We retrospectively reviewed
      the medical records of children who were hospitalized between January 2008 and
      December 2016 with a diagnosis of herpangina or hand-foot-mouth disease (HFMD).
      We identified those children who were prescribed antibiotics for at least 24
      hours during admission. We conducted a retrospective descriptive study to analyze
      data in order to determine the factors associated with pediatrician antibiotics
      prescribing for enterovirus infection. RESULTS: In the nine years of study
      period, the rate of antibiotics use was about 13% in these patients. A total of
      3659 patients were enrolled during 2008~2012 and analyzed in detail. Elevated
      levels of C-reactive protein (CRP) and presence of leukocytosis in blood (WBC)
      were both significantly associated with pediatrician antibiotic prescribing for
      enterovirus infection (p<0.001). Between different specialistic devisions, there
      was significantly different proportion of antibiotics utilization for patients.
      In further analysis of antibiotics prescribing by Receiver operating
      characteristic (ROC) curve method, the level of CRP significantly had more the
      area under curve (0.708) compared with the count of WBC (p<0.05). CONCLUSIONS:
      The present study indicates that higher serum level of CRP is strongly associated
      with pediatricians prescribing antibiotics for children experiencing herpangina
      or HFMD. Antibiotic prescribing is a complex process. Pediatricians should be
      more judicious in decision-making time by their specialistics. Our findings would
      shed new light on process and allay the concern about inappropriate antibiotics.

PMID- 30192894
TI  - Hospital-acquired colonization and infections in a Vietnamese intensive care
      unit.
AB  - Data concerning intensive care unit (ICU)-acquired bacterial colonization and
      infections are scarce from low and middle-income countries (LMICs). ICU patients
      in these settings are at high risk of becoming colonized and infected with
      antimicrobial-resistant organisms (AROs). We conducted a prospective
      observational study at the Ho Chi Minh City Hospital for Tropical Diseases,
      Vietnam from November 2014 to January 2016 to assess the ICU-acquired
      colonization and infections, focusing on the five major pathogens in our setting:
      Staphylococcus aureus (S. aureus), Escherichia coli (E. coli), Klebsiella spp.,
      Pseudomonas spp. and Acinetobacter spp., among adult patients with more than 48
      hours of ICU stay. We found that 61.3% (223/364) of ICU patients became colonized
      with AROs: 44.2% (161/364) with rectal ESBL-producing E. coli and Klebsiella
      spp.; 30.8% (40/130) with endotracheal carbapenemase-producing Acinetobacter
      spp.; and 14.3% (52/364) with nasal methicillin-resistant S. aureus. The
      incidence rate of ICU patients becoming colonized with AROs was 9.8 (223/2,276)
      per 100 patient days. Significant risk factor for AROs colonization was the
      Charlson Comorbidity Index score. The proportion of ICU patients with HAIs was
      23.4% (85/364), and the incidence rate of ICU patients contracting HAIs was 2.3
      (85/3,701) per 100 patient days. The vascular catheterization (central venous,
      arterial and hemofiltration catheter) was significantly associated with hospital
      acquired bloodstream infection. Of the 77 patients who developed ICU-acquired
      infections with one of the five specified bacteria, 44 (57.1%) had prior
      colonization with the same organism. Vietnamese ICU patients have a high
      colonization rate with AROs and a high risk of subsequent infections. Future
      research should focus on monitoring colonization and the development of
      preventive measures that may halt spread of AROs in ICU settings.

PMID- 30192895
TI  - Changes in children's television and computer time according to parental
      education, parental income and ethnicity: A 6-year longitudinal EYHS study.
AB  - OBJECTIVES: To investigate changes in children's television and computer time
      according to three socio-economic status (SES) indicators. DESIGN: Prospective
      cohort study. METHODS: Data were drawn from the European Youth Heart Study and
      included longitudinal data collected in 1997 and 2003 in Denmark. Television and
      computer time were self-reported by children. Parental education, income and
      ethnicity were parent-reported. Baseline data were available for 549 children
      (47.0% boys, 9.6 years). Generalized linear mixed models analyzed whether changes
      in television and computer time from baseline to follow-up differed according to
      the SES-indicators. RESULT: TV viewing time increased with 25% over time (ExpB =
      1.25, 95% CI = 1.04-1.50). At both time points, children with two higher educated
      parents viewed 25% less hours of television than children with no higher educated
      parents (ExpB = 0.75, 95% CI = 0.60-0.94) and one higher educated parent (ExpB =
      0.75, 95%CI = 0.59-0.97). Among children with no higher educated parents the odds
      of being in a higher category of computer time increased with 80% over time (OR =
      1.80, 95% CI = 1.24-2.60). Among children with two higher educated parents the
      odds of being in a higher category of computer time decreased with 45% over time
      (OR = 0.55, 95% CI = 0.32-0.94). The association with ethnicity showed that white
      children had 42% lower odds (OR = 0.58; 95% CI = 0.34-1.00) of being in a higher
      category of computer time than non-white children. No significant associations
      were found for parental income. CONCLUSIONS: The most important SES measure of
      screen-based behaviors in children was parental education. Ethnicity was only
      associated with computer time. Financial resources were less relevant for changes
      in television viewing and computer use.

PMID- 30192896
TI  - Comparative transcriptome analysis of Eriocheir japonica sinensis response to
      environmental salinity.
AB  - Chinese mitten crabs (Eriocheir japonica sinensis) are catadromous, spending most
      of their lives in fresh water, but moving to a mixed salt-fresh water environment
      for reproduction. The characteristics of this life history might imply a rapidly
      evolutionary transition model for adaptation to marine from freshwater habitats.
      In this study, transcriptome-wide identification and differential expression on
      Chinese mitten crab groups were analysed. Results showed: clean reads that were
      obtained totalled 93,833,096 (47,440,998 in Group EF, the reference, and
      46,392,098 in Group ES, the experimental) and 14.08G (7.12G in Group EF 6.96G in
      Group ES); there were 11,667 unigenes (15.29%) annotated, and they were located
      to 230 known KEGG pathways in five major categories; in differential expression
      analysis, most of the top 20 up-regulated pathways were connected to the immune
      system, disease, and signal transduction, while most of the top 20 down-regulated
      pathways were related to the metabolism system; meanwhile, 8 representative
      osmoregulation-related genes (14-3-3 epsilon, Cu2+ transport ATPase, Na+/K+
      ATPase, Ca2+ transporting ATPase, V-ATPase subunit A, Putative arsenite
      translocating ATPase, and Cation transport ATPase, Na+/K+ symporter) showed up
      regulation, and 1 osmoregulation-related gene (V-ATPase subunit H) showed down
      regulation. V-ATPase subunit H was very sensitive to the transition of habitats.
      These results were consistent with the tests of qRT-PCR. The present study has
      provided a foundation to further understand the molecular mechanism in response
      to salinity changing in water.

PMID- 30192897
TI  - A situational analysis of latent tuberculosis infection among incarcerated
      population in Japan.
AB  - BACKGROUND: The World Health Organization recommends that systematic testing and
      screening of latent tuberculosis infection (LTBI) among the incarcerated
      population "should be considered", though based on evidence of either low or very
      low quality. However, in Japan, a TB middle-burden country, systematic screening
      for LTBI in correctional facilities is currently not conducted. As part of a
      larger study to determine the cost-effectiveness of LTBI screening in
      correctional facilities in Japan, this study was conducted to determine the
      situation of LTBI, including treatment outcome, among the incarcerated population
      in Japan, and provide the essential data for cost-effectiveness analysis. METHOD:
      A cross-sectional study was conducted between 2017 and 2018 with public health
      centers which have one or more correctional facilities under their jurisdiction.
      Questionnaire surveys were sent to collect information on their policy of
      managing LTBI patients notified from correctional facilities, including whether
      or not there was a standardized procedure for initiating LTBI treatment, and also
      to collect sociodemographic information and treatment outcome of LTBI patients
      who were notified from the respective correctional facilities in 2015 and 2016.
      RESULTS: The survey was sent to a total of 163 public health centers, out of
      which 133 (81.6%) responded. 8 of the 133 public health centers actively guided
      the correctional facilities regarding LTBI treatment initiation through a
      standardized procedure, while 115 either had not established such procedure or
      were unaware of how LTBI treatment was being initiated in the correctional
      facilities. A total of 91 LTBI patients were notified from the correctional
      facilities in 2015 and 2016, and the information of 89 were available for
      analysis. 82 were males, and 83 were Japan-born. Treatment outcome was known for
      88 patients, of which 70 had completed treatment. Of the 18 who did not complete
      the treatment, 15 had been lost to follow-up upon release from the facilities.
      Among those who had been released whilst on treatment, the proportion of those
      who completed the treatment was higher in those patients who received pre-release
      visit by a public health nurse, than those who did not. CONCLUSIONS: LTBI
      treatment was often being initiated without consideration for the patients'
      prison term. The treatment completion rate within jail was high, indicating the
      possibility that incarcerated population can benefit for LTBI treatment. On the
      other hand, the completion rate decreased significantly among those who had been
      released while still on treatment. In order to optimize the benefit, initiation
      of LTBI must carefully be considered upon the patient's prison term, as well as
      coordination among the relevant organizations to ensure continuity of care after
      release.

PMID- 30192898
TI  - Obligation and negative consequences in primary caregivers of dependent older
      relatives.
AB  - The purpose of this study was to analyse the multidimensional nature of
      obligation and the relations between each dimension of obligation and both
      anxiety and depression. A secondary analysis of data from two cross-sectional
      studies of primary home caregivers (N = 400; probabilistic sample) of older adult
      relatives in Spain was conducted. Data regarding obligation (four categories
      basing on beliefs of obligation and social pressure: low pressure and low
      beliefs, low pressure and high beliefs, high pressure and low beliefs and high
      pressure and high beliefs), stressors, anxiety and depression were collected by
      interview in 2013. The combination of high pressure and low beliefs had the
      highest levels of anxiety and depression, and the combination of low pressure and
      high beliefs had the lowest levels of anxiety and depression. When the relation
      of behavioural problems with anxiety and depression stratified by the previous
      four categories of obligation was analysed, behavioural problems were associated
      with anxiety and depression in the subgroups with low beliefs of obligation,
      whereas this association disappeared in the subgroups with high beliefs of
      obligation.

PMID- 30192899
TI  - Risk stratification and role for additional diagnostic testing in patients with
      acute chest pain and normal high-sensitivity cardiac troponin levels.
AB  - BACKGROUND: Normal high sensitivity cardiac troponin (hs-cTn) assays rule out
      acute myocardial infarction (AMI) with great accuracy, but additional non
      invasive testing is frequently ordered. This observational study evaluates
      whether clinical characteristics can contribute to risk stratification and could
      guide referral for additional testing. METHODS: 918 serial patients with acute
      chest pain and normal hs-cTnT levels were prospectively included. Major adverse
      cardiac events (MACE) and non-invasive test results were assessed during one-year
      follow-up. Patients were classified as low and high risk based on clinical
      characteristics. RESULTS: MACE occurred in 6.1% of patients and mainly comprised
      revascularizations (86%). A recent abnormal stress test, suspicious history, a
      positive family history and higher baseline hs-cTnT levels were independent
      predictors of MACE with odds ratios of 16.00 (95%CI:6.25-40.96), 16.43 (6.36
      42.45), 2.33 (1.22-4.42) and 1.10 (1.01-1.21), respectively. Absence of both
      recent abnormal stress test and suspicious history identified 86% of patients.
      These patients were at very low risk for MACE (0.4% in 30-days and 2.3% in one
      year). Despite this, the majority (287/345 = 83%) of additional tests were
      performed in low risk patients, with <10% abnormal test findings. The diagnostic
      yield was significantly higher in the remaining higher risk patients, 40%
      abnormal test findings and a positive predictive value of 70% for MACE. Similar
      results were observed in patients without known coronary artery disease.
      CONCLUSIONS: Clinical characteristics can be used to identify low risk patients
      with acute chest pain and normal hs-cTnT levels. Current strategies in the
      emergency department result in numerous additional tests, which are mostly
      ordered in patients at very low risk and have a low diagnostic yield.

PMID- 30192900
TI  - Branching morphogenesis of the urinary collecting system in the human embryonic
      metanephros.
AB  - An elaborate system of ducts collects urine from all nephrons, and this structure
      is known as the urinary collecting system (UCS). This study focused on how the
      UCS is formed during human embryogenesis. Fifty human embryos between the
      Carnegie stage (CS) 14 and CS23 were selected from the Kyoto Collection at the
      Congenital Anomaly Research Center of Kyoto University, Japan. Metanephroses,
      including the UCS, were segmented on serial digital virtual histological
      sections. Three-dimensional images were computationally reconstructed for
      morphological and quantitative analyses. A CS timeline was plotted. It consisted
      of the 3-D structural morphogenesis of UCS and quantification of the total amount
      of end-branching, average and maximum numbers of generations, deviation in the
      metanephros, differentiation of the urothelial epithelium in the renal pelvis,
      and timing of the rapid expansion of the renal pelvis. The first UCS branching
      generation occurred by CS16. The average branching generation reached a maximum
      of 8.74 +/- 1.60 and was already the twelfth in CS23. The total end-branching
      number squared between the start and the end of the embryonic period. UCS would
      reach the fifteenth branching generation soon after CS23. The number of nephrons
      per UCS end-branch was low (0.21 +/- 0.14 at CS19, 1.34 +/- 0.49 at CS23),
      indicating that the bifid branching occurred rapidly and that the formation of
      nephrons followed after. The renal pelvis expanded mainly in CS23, which was
      earlier than that reported in a previous study. The number of nephrons connected
      to the UCS in the expanded group (246.0 +/- 13.2) was significantly larger than
      that of the pre-expanded group (130.8 +/- 80.1) (P < 0.05). The urothelial
      epithelium differentiated from the zeroth to the third generations at CS23.
      Differentiation may have continued up until the tenth generation to allow for
      renal pelvis expansion. The branching speed was not uniform. There were
      significantly more branching generations in the polar- than in the interpolar
      regions (P < 0.05). Branching speed reflects the growth orientation required to
      form the metanephros. Further study will be necessary to understand the renal
      pelvis expansion mechanism in CS23. Our CS-based timeline enabled us to map UCS
      formation and predict functional renal capacity after differentiation and growth.

PMID- 30192901
TI  - Correction: Biomechanical Constraints Underlying Motor Primitives Derived from
      the Musculoskeletal Anatomy of the Human Arm.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0164050.].

PMID- 30192902
TI  - Cooperation Makes a Group be More Creative.
AB  - This study investigated how cooperative and competitive interaction modes affect
      the group creative performance. The participants were recruited as dyads to solve
      2 problems either demanding divergent thinking (alternative uses task, AUT) or
      not (object characteristic task, OCT). The dyads solved 1 of the 2 problems in
      the cooperative mode and the other in the competitive mode. Functional near
      infrared spectroscopy (fNIRS)-based hyperscanning was used to record their neural
      activities in the prefrontal and right temporal-parietal junction (r-TPJ)
      regions. Results revealed the dyads showed higher AUT fluency, AUT originality,
      OCT fluency, and cooperation level in the cooperative mode than in the
      competitive mode. The fNIRS data revealed increased (task-baseline) interpersonal
      brain synchronization (IBS) in the right dorsolateral prefrontal cortex (r-DLPFC)
      and r-TPJ, only for dyads in the AUT/cooperation condition. In both r-DLPFC and r
      TPJ, the IBS of dyads in the AUT/cooperation condition was stronger than in the
      AUT/competition and OCT/cooperation. Moreover, a stronger IBS was evoked between
      the regions in prefrontal and posterior temporal regions in the AUT/cooperation
      condition, as compared with the competition mode. These findings suggest that
      enhanced IBS may underlie the positive effects of cooperation as compared with
      the competition in terms of group creativity.

PMID- 30192903
TI  - The joint lasso: high-dimensional regression for group structured data.
AB  - We consider high-dimensional regression over subgroups of observations. Our work
      is motivated by biomedical problems, where subsets of samples, representing for
      example disease subtypes, may differ with respect to underlying regression
      models. In the high-dimensional setting, estimating a different model for each
      subgroup is challenging due to limited sample sizes. Focusing on the case in
      which subgroup-specific models may be expected to be similar but not necessarily
      identical, we treat subgroups as related problem instances and jointly estimate
      subgroup-specific regression coefficients. This is done in a penalized framework,
      combining an $?ell_1$ term with an additional term that penalizes differences
      between subgroup-specific coefficients. This gives solutions that are globally
      sparse but that allow information-sharing between the subgroups. We present
      algorithms for estimation and empirical results on simulated data and using
      Alzheimer's disease, amyotrophic lateral sclerosis, and cancer datasets. These
      examples demonstrate the gains joint estimation can offer in prediction as well
      as in providing subgroup-specific sparsity patterns.

PMID- 30192904
TI  - Mixed Graphical Models for Integrative Causal Analysis with Application to
      Chronic Lung Disease Diagnosis and Prognosis.
AB  - Motivation: Integration of data from different modalities is a necessary step for
      multi-scale data analysis in many fields, including biomedical research and
      systems biology. Directed graphical models offer an attractive tool for this
      problem because they can represent both the complex, multivariate probability
      distributions and the causal pathways influencing the system. Graphical models
      learned from biomedical data can be used for classification, biomarker selection
      and functional analysis, while revealing the underlying network structure and
      thus allowing for arbitrary likelihood queries over the data. Results: In this
      paper, we present and test new methods for finding directed graphs over mixed
      data types (continuous and discrete variables). We used this new algorithm,
      CausalMGM, to identify variables directly linked to disease diagnosis and
      progression in various multi-modal datasets, including clinical datasets from
      chronic obstructive pulmonary disease (COPD). COPD is the third leading cause of
      death and a major cause of disability and thus determining the factors that cause
      longitudinal lung function decline is very important. Applied on a COPD dataset,
      mixed graphical models were able to confirm and extend previously described
      causal effects and provide new insights on the factors that potentially affect
      the longitudinal lung function decline of COPD patients. Availability: The
      CausalMGM package is available on CRAN. Supplementary information: Supplementary
      data are available at Bioinformatics online.

PMID- 30192905
TI  - Aortic Ambulatory Blood Pressure Monitoring and Target Organ Damage: Are the Data
      Really Conflicting?

PMID- 30192906
TI  - Loose Ends in the Epidemiology of the 1918 Pandemic: Explaining the Extreme
      Mortality Risk in Young Adults.
AB  - In the century since the 1918 influenza pandemic, insights have been sought to
      explain the pandemic's signature pattern of high death rates in young adults and
      low death rates in the elderly and infants. Our understanding of the origin and
      evolution of the pandemic has shifted considerably. We review evidence of the
      characteristic age-related pattern of death during the 1918 pandemic relative to
      the "original antigenic sin" hypothesis. We analyze age-stratified mortality data
      from Copenhagen around 1918 to identify break points associated with unusual
      death risk. Whereas infants had no meaningful risk elevation, death risk
      gradually increased, peaking for young adults 20-34 years of age before dropping
      sharply for adults ages 35-44 years, suggesting break points for birth cohorts
      around 1908 and 1878. Taken together with data from previous studies, there is
      strong evidence that those born before 1878 or after 1908 were not at increased
      risk of dying of 1918 pandemic influenza. Although the peak death risk coincided
      with the 1889-1892 pandemic, the 1908 and 1878 break points do not correspond
      with known pandemics. An increasing number of interdisciplinary studies covering
      fields such as virology, phylogenetics, death, and serology offer exciting
      insights into patterns and reasons for the unusual extreme 1918 pandemic
      mortality risk in young adults.

PMID- 30192907
TI  - Efficacy of Contextually Tailored Suggestions for Physical Activity: A Micro
      randomized Optimization Trial of HeartSteps.
AB  - Background: HeartSteps is an mHealth intervention that encourages regular walking
      via activity suggestions tailored to the individuals' current context. Purpose:
      We conducted a micro-randomized trial (MRT) to evaluate the efficacy of
      HeartSteps' activity suggestions to optimize the intervention. Methods: We
      conducted a 6-week MRT with 44 adults. Contextually tailored suggestions could be
      delivered up to five times per day at user-selected times. At each of these five
      times, for each participant on each day of the study, HeartSteps randomized
      whether to provide an activity suggestion, and, if so, whether to provide a
      walking or an antisedentary suggestion. We used a centered and weighted least
      squares method to analyze the effect of suggestions on the 30-min step count
      following suggestion randomization. Results: Averaging over study days and types
      of activity suggestions, delivering a suggestion versus no suggestion increased
      the 30-min step count by 14% (p = .06), 35 additional steps over the 253-step
      average. The effect was not evenly distributed in time. Providing any type of
      suggestion versus no suggestion initially increased the step count by 66% (167
      steps; p < .01), but this effect diminished over time. Averaging over study days,
      delivering a walking suggestion versus no suggestion increased the average step
      count by 24% (59 steps; p = .02). This increase was greater at the start of study
      (107% or 271 additional steps; p < .01), but decreased over time. Antisedentary
      suggestions had no detectable effect on the 30-min step count. Conclusion:
      Contextually tailored walking suggestions are a promising way of initiating bouts
      of walking throughout the day. Clinical Trial information: This study was
      registered on ClinicalTrials.gov number NCT03225521.

PMID- 30192908
TI  - Detailed Sonographic Anatomy of Dorsal Hand Augmentation With Hyaluronidase and
      Calcium Hydroxyapatite Fillers.
AB  - Background: Volume restoration using filler in the dorsum of the hand is a simple
      and effective procedure to improve wrinkles and to hide veins and tendons.
      Currently, Calcium-Hydroxyapatite (CaHA)-filler is the only FDA-accepted material
      to use in the hand dorsum. However, it is not easy to inject due to swelling and
      redness. In addition, hand anatomy through sonography is wrongly described in
      PRS. Through incorrect anatomy, physicians will make erroneous surgeries.
      Objectives: CaHA-filler and HA-filler were both injected into the hand to compare
      intra-individually the effect of each filler. Through this study, the author
      introduces detailed and refined sonographic anatomy. Overall, the author
      identifies the correct injection method and depth. Methods: In this prospective
      intra-individual comparative study, patients were injected 1cc of CaHA-filler to
      the left hand and 3cc (36mg) of microphasic hyaluronic acid to the right.
      Outcomes were assessed by Merz hand grading scale (MHGS), skin bio-parameters,
      dermascopic finding, and Global Aesthetic Improvement Scale (GAIS) with follow-up
      at 3, 6, 9, and 12 months. Results: The average GAIS score improved in both hands
      and generally maintained over the course of the study. There was significantly
      more bruising and swelling in the CaHA injected hands compare to the HA injected
      hands. The skin roughness and appearance improved in both sets of hands on
      dermascope. The average Trans-Epidermal-Water-Loss (TEWL) decreased and the
      average Stratum Corneum Hydration (SCH) increased in HA injected hands. The
      biopsy study showed that the HA particles lasted for 9 months. Conclusions: The
      author reestablished sonographic anatomy for the first time. Veins and tendons
      became less apparent after injections.

PMID- 30192909
TI  - Reclassification Of Hypertensive Outpatients According To New United States
      Guidelines On High Blood Pressure.
AB  - Background: United States (US) guidelines on high blood pressure (BP) have
      recently proposed a new BP stratification. Objective: To evaluate the
      redistribution of adult outpatients according to 2003 and 2017 US hypertension
      guidelines. Methods: We extracted data referred to individuals aged between 40-70
      years with valid BP assessment from a national, cross-sectional database. The
      following systolic/diastolic BP strata were considered: a) 2003 guidelines:
      0=normal (<120/180 mmHg); 1=prehypertension (>=120 and <=139/>=80 and <=89 mmHg);
      2=stage 1 (>=140 and <=159/>=90 and <=99 mmHg); 3=stage 2 (>=160/>=100 mmHg); b)
      2017 ACC/AHA guidelines: 0=normal (<120/80 mmHg); 1=elevated (>=120 and <=129/<80
      mmHg); 2=stage 1 (>=130 and <=139/>=80 and <=89 mmHg); 3=stage 2 (>=140/>=90
      mmHg). CV risk profile characterization was based on Framingham, ASCVD and
      European score equations. Results: From an overall population sample of 10,012
      individuals, we selected 8,911 (89.0%) with valid clinic BP data (44.4% female,
      age 60.76.6 years, BMI 28.24.9 kg/m2, clinic BP 136.814.5/82.18.3 mmHg), among
      whom 339 (3.8%) were in the normal BP range. According to 2003 guidelines, 3,919
      (44.0%) patients had pre-hypertension, 3,698 (41.5%) stage 1 and 955 (10.7%)
      stage 2 hypertension. According to 2017 guidelines, 635 (3.8%) patients had
      elevated BP, 3284 (36.9%) stage 1 and 4653 (52.2%) stage 2 hypertension. New BP
      classification moved 37% individuals from "pre-hypertension" to "stage 1" and 41%
      from "stage 1" to "stage 2" hypertension, respectively. Conclusions:
      Redistribution of hypertensive patients according to 2017 US hypertension
      guidelines compared to previous ones may help to better identify uncontrolled
      hypertensive patients with high CV risk profile.

PMID- 30192910
TI  - FOUR AUTHORS REPLY.

PMID- 30192911
TI  - Inference and visualization of DNA damage patterns using a Grade of Membership
      Model.
AB  - Motivation: Quality control plays a major role in the analysis of ancient DNA
      (aDNA). One key step in this quality control is assessment of DNA damage: aDNA
      contains unique signatures of DNA damage that distinguish it from modern DNA, and
      so analyses of damage patterns can help confirmthat DNA sequences obtained are
      from endogenous aDNA rather than from modern contamination. Predominant
      signatures of DNA damage include a high frequency of cytosine to thymine
      substitutions (C-to-T) at the ends of fragments, and elevated rates of purines (A
      & G) before the 5' strand-breaks. Existing QC procedures help assess damage by
      simply plotting for each sample, the C-to-T mismatch rate along the read and the
      composition of bases before the 5' strand-breaks. Here we present a more flexible
      and comprehensive model-based approach to infer and visualize damage patterns in
      aDNA, implemented in an R package aRchaic. This approach is based on a "grade of
      membership" model (also known as "admixture" or "topic" model) in which each
      sample has an estimated grade of membership in each of K damage profiles that are
      estimated from the data. Results: We illustrate aRchaic on data from several aDNA
      studies and modern individuals from 1000 Genomes Project Consortium (2012). Here,
      aRchaic clearly distinguishes modern from ancient samples irrespective of DNA
      extraction, lab and sequencing protocols. Additionally, through an in-silico
      contamination experiment, we show that the aRchaic grades of membership reflect
      relative levels of exogenous modern contamination. Together, the outputs of
      aRchaic provide a concise visual summary of DNA damage patterns, as well as other
      processes generating mismatches in the data. Availability: aRchaic is available
      for download from https://www.github.com/kkdey/aRchaic. Supplementary
      Information: Supplementary data are available at Bioinformatics online.

PMID- 30192912
TI  - Response to Letter-to-the-Editor Re: "Invited commentary: Diesel exhaust and lung
      cancer - aftermath of becoming an IARC Group 1 carcinogen" by Ellen T. Chang,
      Edmund C. Lau, Cynthia Van Landingham, Kenny S. Crump, Roger O. McClellan, Suresh
      H. Moolgavkar.

PMID- 30192913
TI  - Three-Dimensional Computed Tomographic Study on the Periorbital Branches of the
      Ophthalmic Artery: Arterial Variations and Clinical Relevance.
AB  - Background: Filler injection is a popular cosmetic procedure, but it can entail
      vascular complications. Periorbital injections have the highest risk among all
      the injection area. Objectives: To systematically screen for periorbital arterial
      variations prior to treatment. Methods: The external carotid arteries of 10
      cadaveric heads were infused with adequate lead oxide contrast. The facial and
      superficial temporal arteries of another 11 cadaveric heads were injected with
      the contrast in sequential order. Computed tomography (CT) scanning was performed
      after injection of contrast, and three-dimensional (3D) CT scans were
      reconstructed using validated algorithms. Results: Three types of periorbital
      blood vessels were found to derive from the ophthalmic artery, including 30%
      directly originating from the ophthalmic artery; 65% originating from its
      trochlear branch; and 5% originating from its supraorbital branch. In the
      forehead, the ophthalmic artery, originating from the internal carotid arteries,
      formed anastomoses between the frontal branch of the superficial temporal artery,
      originating from the external carotid artery, with the deep and superficial
      branches of the supratrochlear and supraorbital arteries, respectively. The
      lateral orbit and malar plexus can be classified into four types based on the
      trunk artery: the zygomatic orbital artery (27%), the transverse facial artery
      (23%), the premasseteric branch of the facial artery (19%), and all three
      contributing equally (31%). Conclusions: Postmortem 3D CT can map periorbital
      arterial variations. The branching pattern of the ophthalmic artery, the
      ophthalmic angiosome in the forehead, and the distribution of the lateral orbit
      and malar plexus were identified at high resolution to guide clinical practice.

PMID- 30192914
TI  - Mineralocorticoid Receptor and Cardiovascular Disease.
AB  - Activation of the mineralocorticoid receptor (MR) in the distal nephron by its
      ligand, aldosterone, plays an important role in sodium reabsorption and blood
      pressure regulation. However, expression of the MR goes beyond the kidney. It is
      expressed in a variety of other tissues in which its activation could lead to
      tissue injury. Indeed, MR activation in the cardiovascular (CV) system has been
      shown to promote hypertension, fibrosis, and inflammation. Pharmacological
      blockade of the MR has protective effects in several animal models of CV disease.
      Furthermore, the use of MR antagonists is beneficial for heart failure patients,
      preventing mortality and morbidity. A better understanding of the implications of
      the MR in the setting of CV diseases is critical for refining treatments and
      improving patient care. The mechanisms involved in the deleterious effects of MR
      activation are complex and include oxidative stress, inflammation, and fibrosis.
      This review will discuss the pathological role of the MR in the CV system and the
      major mechanisms underlying it.

PMID- 30192915
TI  - Acute, local infusion of angiotensin II impairs microvascular and metabolic
      insulin sensitivity in skeletal muscle.
AB  - Aims: Angiotensin II (AngII) is a potent vasoconstrictor implicated in both
      hypertension and insulin resistance. Insulin dilates the vasculature in skeletal
      muscle to increase microvascular blood flow and enhance glucose disposal. In the
      present study, we investigated whether acute AngII infusion interferes with
      insulin's microvascular and metabolic actions in skeletal muscle. Methods and
      Results: Adult, male Sprague-Dawley rats received a systemic infusion of either
      saline, AngII, insulin (hyperinsulinemic euglycemic clamp) or insulin
      (hyperinsulinemic euglycemic clamp) plus AngII. A final, separate group of rats
      received an acute local infusion of AngII into a single hindleg during systemic
      insulin (hyperinsulinemic euglycemic clamp) infusion. In all animals systemic
      metabolic effects, central hemodynamics, femoral artery blood flow, microvascular
      blood flow and skeletal muscle glucose uptake (isotopic glucose) were monitored.
      Systemic AngII infusion increased blood pressure, decreased heart rate and
      markedly increased circulating glucose and insulin concentrations. Systemic
      infusion of AngII during hyperinsulinemic euglycemic clamp inhibited insulin
      mediated suppression of hepatic glucose output and insulin-stimulated
      microvascular blood flow in skeletal muscle but did not alter insulin's effects
      on the femoral artery or muscle glucose uptake. Local AngII infusion did not
      alter blood pressure, heart rate or circulating glucose and insulin. However,
      local AngII inhibited insulin-stimulated microvascular blood flow and this was
      accompanied by reduced skeletal muscle glucose uptake. Conclusions: Acute
      infusion of AngII significantly alters basal haemodynamic and metabolic
      homeostasis in rats. Both local and systemic AngII infusion attenuated insulin's
      microvascular actions in skeletal muscle, but only local AngII infusion led to
      reduced insulin-stimulated muscle glucose uptake. While increased local, tissue
      production of AngII may be a factor that couples microvascular insulin resistance
      and hypertension, additional studies are needed to determine the molecular
      mechanisms responsible for these vascular defects.

PMID- 30192916
TI  - Frailty among patients receiving hemodialysis: evolution of components and
      associations with mortality.
AB  - Background: Understanding how components of frailty change over time and how they
      can be modeled as time-dependent predictors of mortality could lead to better
      risk prediction in the dialysis population. Methods: We measured frailty at
      baseline, 12, and 24 months among 727 patients receiving hemodialysis in Northern
      California and Atlanta. We examined the likelihood of meeting frailty components
      (weight loss, exhaustion, low physical activity, weak grip strength, and slow
      gait speed) as a function of time in logistic regression analysis and association
      of frailty components with mortality in time-updated multivariable Cox models.
      Results: Physical activity and gait speed declined, exhaustion and grip strength
      did not change, and the odds of meeting the weight loss criterion declined with
      time. All five components were associated with higher mortality in multivariable
      analyses, but gait speed was the strongest individual predictor. All frailty
      components except physical inactivity were independently associated with
      mortality when all five components were included in the same model. The number of
      frailty components met was associated with mortality in a gradient that ranged
      from a HR of 2.73 for one component to 10.07 for five components met; the model
      including all five components was the best model based on Akaike information
      criterion. Conclusions: Measurement of all frailty components was necessary for
      optimal mortality prediction, and the number of components met was strongly
      associated with mortality in this cohort.

PMID- 30192917
TI  - Interaction Effects between the Cumulative Genetic Score and Psychosocial
      Stressor on Self-Reported Drinking Urge and Implicit Attentional Bias for
      Alcohol: A Human Laboratory Study.
AB  - Aims: The current candidate gene and environment interaction (cGxE) study
      examined whether the effects of an experimentally manipulated psychosocial
      stressor on self-reported drinking urge and implicit attentional bias for alcohol
      cues differ as a function of a cumulative genetic score of 5-HTTLPR, MAO-A, DRD4,
      DAT1 and DRD2 genotypes. The current study also examined whether salivary alpha
      amylase level or self-reported anxiety state mediate these cGxE effects. Short
      Summary: Individuals with high cumulative genetic risk score of the five
      monoamergic genotypes showed greater attentional bias toward alcohol cues when
      exposed to a psychosocial stressor than when not exposed. Methods: Frequent binge
      drinking Caucasian young adults (N = 105; mean age = 19; 61% male) completed both
      the control condition and stress condition (using the Trier Social Stress Test)
      in order. Results: Regarding attentional bias, individuals with high and medium
      cumulative genetic risk scores showed greater attentional bias toward alcohol
      stimuli in the stress condition than in the control condition, whereas, those
      with low genetic risk scores showed greater attentional bias toward alcohol
      stimuli in the control condition than in the stress condition. No mediating roles
      of salivary alpha-amylase and anxiety state in the cGxE effect were found.
      Regarding self-reported drinking urge, individuals with high cumulative genetic
      score reported greater drinking urge than those with low genetic score regardless
      of experimental conditions. Conclusions: Although replication is necessary, the
      findings suggest that the association of a psychosocial stressor on implicit (but
      not explicit, self-reported) alcohol outcomes may differ as a function of the
      collective effects of five monoamine genes.

PMID- 30192918
TI  - Ambiguous splice sites distinguish circRNA and linear splicing in the human
      genome.
AB  - Motivation: Identification of splice sites is critical to gene annotation and to
      determine which sequences control circRNA biogenesis. Full-length RNA transcripts
      could in principle complete annotations of introns and exons in genomes without
      external ontologies, i.e., ab initio. However, whether it is possible to
      reconstruct genomic positions where splicing occurs from full-length transcripts,
      even if sampled in the absence of noise, depends on the genome sequence
      composition. If it is not, there exist provable limits on the use of RNA-Seq to
      define splice locations (linear or circular) in the genome. Results: We provide a
      formal definition of splice site ambiguity due to the genomic sequence by
      introducing a definition of equivalent junction, which is the set of local
      genomic positions resulting in the same RNA sequence when joined through RNA
      splicing. We show that equivalent junctions are prevalent in diverse eukaryotic
      genomes and occur in 88.64% and 78.64% of annotated human splice sites in linear
      and circRNA junctions, respectively. The observed fractions of equivalent
      junctions and the frequency of many individual motifs are statistically
      significant when compared against the null distribution computed via simulation
      or closed-form. The frequency of equivalent junctions establishes a fundamental
      limit on the possibility of ab initio reconstruction of RNA transcripts without
      appealing to the ontology of "GT-AG" boundaries defining introns. Said
      differently, completely ab initio is impossible in the vast majority of splice
      sites in annotated circRNAs and linear transcripts. Availability: Two python
      scripts generating an equivalent junction sequence per junction are available at:
      https://github.com/salzmanlab/Equivalent-Junctions. Supplementary information:
      Supplementary data are available at Bioinformatics online.

PMID- 30192919
TI  - Response to "Invited commentary: diesel exhaust and lung cancer -- aftermath of
      becoming an IARC Group 1 carcinogen" by Debra T. Silverman. Am J Epidemiol 2018
      Mar 7. doi: 10.1093/aje/kwy036.

PMID- 30192920
TI  - smCounter2: an accurate low-frequency variant caller for targeted sequencing data
      with unique molecular identifiers.
AB  - Motivation: Low-frequency DNA mutations are often confounded with technical
      artifacts from sample preparation and sequencing. With unique molecular
      identifiers (UMIs), most of the sequencing errors can be corrected. However,
      errors before UMI tagging, such as DNA polymerase errors during end-repair and
      the first PCR cycle, cannot be corrected with single-strand UMIs and impose
      fundamental limits to UMI-based variant calling. Results: We developed
      smCounter2, a UMI-based variant caller for targeted sequencing data and an
      upgrade from the current version of smCounter. Compared to smCounter, smCounter2
      features lower detection limit that decreases from 1% to 0.5%, better overall
      accuracy (particularly in non-coding regions), a consistent threshold that can be
      applied to both deep and shallow sequencing runs, and easier use via a Docker
      image and code for read pre-processing. We benchmarked smCounter2 against several
      state-of-the-art UMI-based variant calling methods using multiple datasets and
      demonstrated smCounter2's superior performance in detecting somatic variants. At
      the core of smCounter2 is a statistical test to determine whether the allele
      frequency of the putative variant is significantly above the background error
      rate, which was carefully modeled using an independent dataset. The improved
      accuracy in non-coding regions was mainly achieved using novel repetitive region
      filters that were specifically designed for UMI data. Availability: The entire
      pipeline is available at https://github.com/qiaseq/qiaseq-dna under MIT license.
      Supplementary Information: Supplementary data are available at Bioinformatics
      online.

PMID- 30192921
TI  - Prediction of protein group function by iterative classification on functional
      relevance network.
AB  - Motivation: Biological experiments including proteomics and transcriptomics
      approaches often reveal sets of proteins that are most likely to be involved in a
      disease/disorder. To understand the functional nature of a set of proteins, it is
      important to capture the function of the proteins as a group, even in cases where
      function of individual proteins is not known. In this work, we propose a model
      that takes groups of proteins found to work together in a certain biological
      context, integrates them into functional relevance networks, and subsequently
      employs an iterative inference on graphical models to identify group functions of
      the proteins, which are then extended to predict function of individual proteins.
      Results: The proposed algorithm, iterative Group Function Prediction (iGFP),
      depicts proteins as a graph that represents functional relevance of proteins
      considering their known functional, proteomics, and transcriptional features.
      Proteins in the graph will be clustered into groups by their mutual functional
      relevance, which is iteratively updated using a probabilistic graphical model,
      the conditional random field (CRF). iGFP showed robust accuracy even when
      substantial amount of GO annotations were missing. The perspective of "group"
      function annotation opens up novel approaches for understanding functional nature
      of proteins in biological systems. Availability: http://kiharalab.org/iGFP/.

PMID- 30192922
TI  - RE: "PRENATAL EXPOSURE TO ACETAMINOPHEN AND RISK FOR ATTENTION DEFICIT
      HYPERACTIVITY DISORDER AND AUTISTIC SPECTRUM DISORDER: A SYSTEMATIC REVIEW, META
      ANALYSIS, AND META-REGRESSION ANALYSIS OF COHORT STUDIES".

PMID- 30192923
TI  - VarSelLCM: an R/C ++ package for variable selection in model-based clustering of
      mixed-data with missing values.
AB  - Summary: VarSelLCM allows a full model selection (detection of the relevant
      features for clustering and selection of the number of clusters) in model-based
      clustering, according to classical information criteria. Data to be analyzed can
      be composed of continuous, integer and/or categorical features. Moreover, missing
      values are managed, without any pre-processing, by the model used to cluster with
      the assumption that values are missing completely at random. Thus, VarSelLCM also
      allows data imputation by using mixture models. A Shiny application is
      implemented to easily interpret the clustering results. Availability: VarSelLCM
      is available to download at https://CRAN.R-project.org/package=VarSelLCM/.
      Tutorial: vignette is available online at http://varsellcm.r-forge.r
      project.org/. Supplementary information: Supplementary materials are available at
      Bioinformatics online.

PMID- 30192925
TI  - Safety, tolerability and efficacy of generic dolutegravir (DTG) containing ART
      regimens among South Indian HIV-infected patients.
AB  - In this first study of generic dolutegravir (DTG)-containing regimens in a low
      resource setting we assessed safety, tolerability and efficacy within a
      prospective cohort of 564 patients with at least 6 months of clinical follow-up.
      We provide support for a large-scale transition to DTG as part of first-line
      regimens.

PMID- 30192924
TI  - Case-Control Study of Cryptosporidium Transmission in Bangladeshi Households.
AB  - Background: Cryptosporidium is a leading contributor to diarrheal morbidity and
      mortality in under-5 children worldwide. As there is no vaccine and no effective
      drug therapy in young children for this infection, preventing infection is
      critical. We undertook a pilot case-control study to define the extent of person
      to-person transmission of cryptosporidiosis within an urban and a rural community
      in Bangladesh. Methods: We enrolled 48 case families with a Cryptosporidium
      infected child aged 6-18 months. Controls were age- and sex-matched
      Cryptosporidium-negative children in 12 households. Children and household
      members were followed for 8 weeks with weekly illness survey and stool testing
      with quantitative polymerase chain reaction for Cryptosporidium. Results: In the
      24 urban case families, the secondary attack rate was 35.8% (19/53) vs 0% (0/11)
      in controls (P = .018, chi2 test). In contrast, in the 24 rural case families,
      the secondary attack rate was 7.8% (5/64) vs 0% (0/21) in controls (P = .19, chi2
      test). Genotyping by gp60 demonstrated infection with the same subspecies in 5
      families, and evidence of transmission in 2. Serologic response to
      Cryptosporidium infection was associated with younger age, longer duration of
      infection, and Cryptosporidium hominis gp60_IbA9G3R2 infection. Conclusions: In
      the urban site, the high rate of secondary infection and infection with the same
      subspecies within families suggests that person-to-person transmission is a major
      source of Cryptosporidium infection for young children living in this region.
      Molecular genotyping can be applied to determine transmission of Cryptosporidium
      in endemic regions. Further work is needed to understand the differences in
      parasite transmissibility and immunity to different genotypes.

PMID- 30192926
TI  - GSK3beta Inhibition Restores Impaired Neurogenesis in Preterm Neonates With
      Intraventricular Hemorrhage.
AB  - Intraventricular hemorrhage (IVH) is a common complication of prematurity in
      infants born at 23-28 weeks of gestation. Survivors exhibit impaired growth of
      the cerebral cortex and neurodevelopmental sequeale, but the underlying
      mechanism(s) are obscure. Previously, we have shown that neocortical neurogenesis
      continues until at least 28 gestational weeks. This renders the prematurely born
      infants vulnerable to impaired neurogenesis. Here, we hypothesized that
      neurogenesis is impaired by IVH, and that signaling through GSK3beta, a critical
      intracellular kinase regulated by Wnt and other pathways, mediates this effect.
      These hypotheses were tested observationally in autopsy specimens from premature
      infants, and experimentally in a premature rabbit IVH model. Significantly, in
      premature infants with IVH, the number of neurogenic cortical progenitor cells
      was reduced compared with infants without IVH, indicating acutely decreased
      neurogenesis. This finding was corroborated in the rabbit IVH model, which
      further demonstrated reduction of upper layer cortical neurons after longer
      survival. Both the acute reduction of neurogenic progenitors, and the subsequent
      decrease of upper layer neurons, were rescued by treatment with AR-A014418, a
      specific inhibitor of GSK3beta. Together, these results indicate that IVH impairs
      late stages of cortical neurogenesis, and suggest that treatment with GSK3beta
      inhibitors may enhance neurodevelopment in premature infants with IVH.

PMID- 30192928
TI  - Anticholinergic Amnesia is Mediated by Alterations in Human Network Connectivity
      Architecture.
AB  - Disrupted cholinergic neurotransmission plays a central role in Alzheimer's
      disease, medication-induced memory impairment, and delirium. At the systems
      level, this suggests anticholinergic drugs may alter the activity and interplay
      of anatomically distributed neural networks critical for memory function. Using a
      network-sensitive imaging technique (functional connectivity MRI) and a double
      blind, crossover design, we examined the consequences of anticholinergic drug
      administration on episodic memory and functional network architecture in a group
      of clinically normal elderly. We observed that low-dose scopolamine (0.2 mg IV)
      decreased episodic memory performance and selectively decreased connectivity
      strength in 3 of 7 cortical networks. Both memory and connectivity effects were
      independent of beta-amyloid burden. Drug-induced connectivity changes within the
      Default and Salience networks, as well as reductions in the strength of
      anticorrelation between these 2 networks, were sufficient to fully statistically
      mediate the effects of scopolamine on memory performance. These results provide
      experimental support for the importance of the Default and Salience networks to
      memory performance and suggest scopolamine-induced amnesia is underpinned by
      disrupted connectivity within and between these 2 networks. More broadly, these
      results support the potential utility of fcMRI as tool examine the systems-level
      pharmacology of psychoactive drugs.

PMID- 30192927
TI  - Complement 5a Receptor Polymorphisms Are Associated With Panton-Valentine
      Leukocidin-positive Staphylococcus aureus Colonization in African Pygmies.
AB  - Panton-Valentine leukocidin (PVL) is common in African Staphylococcus aureus and
      can be associated with skin and soft tissue infection. PVL-positive S. aureus
      colonization is associated with a variant of complement receptor 5a, the cellular
      target of the lukS PVL subunit.

PMID- 30192929
TI  - A Lab-Based Study of Temperate Forest Termite Impacts on Two Common Wood-Rot
      Fungi.
AB  - Termites and fungi are the primary decomposers of dead wood. Interactions between
      wood-feeding termites and wood-rot fungi are inevitable given their shared food
      source. Termites have developed multiple defense strategies against infectious
      fungi, such as Metarhizium spp., that include antifungal proteins in their saliva
      and fungal inhibition properties in their gut. The antifungal properties of
      termite salivary secretions depend on beta-1,3-glucanases that are likely to be
      effective against a broad spectrum of filamentous fungi. Given the overlap in
      niches, there is opportunity for interference competition between termites and
      wood-rot fungi to occur. Here we demonstrate that beta-1,3-glucanases in the
      saliva and the antifungal properties of the gut of the eastern subterranean
      termite Reticulitermes flavipes (Kollar) (Blattodea: Rhinotermitidae) affects the
      growth of two common wood-rot fungi, Gloeophyllum trabeum Persoon (Murrill)
      (Gloeophyllales: Gloeophyllaceae) and Phanerochaete chrysosporium (Burdsall)
      (Polyporales: Phanerochaetaceae).

PMID- 30192930
TI  - Effect of Oral beta-blocker Treatment on Mortality in Contemporary Post
      myocardial Infarction Patients.
AB  - Aims: Guidelines concerning beta-blocker treatment following acute myocardial
      infarction (AMI) are based on studies undertaken before the implementation of
      reperfusion and secondary prevention therapies. We aimed to estimate the effect
      of oral beta-blockers on mortality in contemporary post-AMI patients with low
      prevalence of heart failure (HF) and/or reduced left ventricular ejection
      fraction (LVEF). Methods and Results: A random effects model was used to
      synthetize results of 16 observational studies published between January 1st 2000
      and October 30th 2017. Publication bias was evaluated, and heterogeneity between
      studies examined by subgroup and random effects meta-regression analyses
      considering patient-related and study-level variables. The pooled estimate showed
      that beta-blocker treatment (among 164 408 [86.8%] patients, with median follow
      up time of 2.7 years) was associated with a 26% reduction in all-cause mortality
      (RR = 0.74, 95% CI: 0.64 to 0.85) with moderate heterogeneity (I2=67.4%). The
      patient-level variable mean age of the cohort explained 31.5% of between study
      heterogeneity. There was presence of publication bias, or small study effect, and
      when controlling for bias by the trim and fill simulation method, the effect
      disappeared (adjusted RR = 0.90, 95% CI: 0.77 to 1.04). Also, small study effect
      was demonstrated by a cumulative meta-analysis starting with the largest study
      showing no effect, with increasing effect as the smaller studies were
      accumulated. Conclusions: Evidence from this study suggests that there is no
      association between beta-blockers and all-cause mortality. A possible beneficial
      effect in AMI survivors needs to be tested by large randomised clinical trials.

PMID- 30192931
TI  - In Vivo Femtosecond Laser Subsurface Cortical Microtransections Attenuate Acute
      Rat Focal Seizures.
AB  - Recent evidence shows that seizures propagate primarily through supragranular
      cortical layers. To selectively modify these circuits, we developed a new
      technique using tightly focused, femtosecond infrared laser pulses to make as
      small as ~100 um-wide subsurface cortical incisions surrounding an epileptic
      focus. We use this "laser scalpel" to produce subsurface cortical incisions
      selectively to supragranular layers surrounding an epileptic focus in an acute
      rodent seizure model. Compared with sham animals, these microtransections
      completely blocked seizure initiation and propagation in 1/3 of all animals. In
      the remaining animals, seizure frequency was reduced by 2/3 and seizure
      propagation reduced by 1/3. In those seizures that still propagated, it was
      delayed and reduced in amplitude. When the recording electrode was inside the
      partially isolated cube and the seizure focus was on the outside, the results
      were even more striking. In spite of these microtransections, somatosensory
      responses to tail stimulation were maintained but with reduced amplitude. Our
      data show that just a single enclosing wall of laser cuts limited to
      supragranular layers led to a significant reduction in seizure initiation and
      propagation with preserved cortical function. Modification of this concept may be
      a useful treatment for human epilepsy.

PMID- 30192932
TI  - It's All in the Details: Relations Between Young Children's Developing Pattern
      Separation Abilities and Hippocampal Subfield Volumes.
AB  - The ability to keep similar experiences separate in memory is critical for
      forming unique and lasting memories, as many events share overlapping features
      (e.g., birthday parties, holidays). Research on memory in young children suggests
      their memories often lack high-resolution details, i.e., show impoverished
      pattern separation (PS). Recently developed assessments of PS suitable for
      children allow us to relate the formation of distinct, detailed memories for the
      development of the hippocampus, a neural structure critical for this ability in
      adults. The hippocampus displays a protracted developmental profile and underlies
      the ability to form detailed memories. This study examined age-related
      differences in hippocampal subfield volumes in 4- to 8-year-old children and
      relations with performance on a mnemonic similarity task (MST) designed to index
      memory specificity. Results revealed age-moderated associations between MST
      performance and cornu ammonis 2-4/dentate gyrus subfields. Specifically, age
      related differences in the ability to form detailed memories tracked with
      normative patterns of volume increases followed by reductions over this age
      range. That is, greater volume correlated with better performance in younger
      children, whereas smaller volume correlated with better performance in older
      children. These findings support the hypothesis that developmental differences in
      hippocampal circuitry contribute to age-related improvements in detailed memory
      formation during this period.

PMID- 30192934
TI  - Optimal modality selection in external beam radiotherapy.
AB  - The goal in external beam radiotherapy (EBRT) for cancer is to maximize damage to
      the tumour while limiting toxic effects on the organs-at-risk. EBRT can be
      delivered via different modalities such as photons, protons and neutrons. The
      choice of an optimal modality depends on the anatomy of the irradiated area and
      the relative physical and biological properties of the modalities under
      consideration. There is no single universally dominant modality. We present the
      first-ever mathematical formulation of the optimal modality selection problem. We
      show that this problem can be tackled by solving the Karush-Kuhn-Tucker
      conditions of optimality, which reduce to an analytically tractable quartic
      equation. We perform numerical experiments to gain insights into the effect of
      biological and physical properties on the choice of an optimal modality or
      combination of modalities.

PMID- 30192935
TI  - Reactive Oxygen Species Emissions from Supra- and Sub-Ohm Electronic Cigarettes.
AB  - Electronic cigarettes (ECIGs) are battery-powered devices that heat and vaporize
      solutions containing propylene glycol (PG) and/or vegetable glycerin (VG),
      nicotine and possible trace flavorants to produce an inhalable aerosol. The
      heating process can lead to the formation of reactive oxygen species (ROS), which
      are linked to various oxidative damage-initiated diseases. Several studies in the
      literature have addressed ROS emissions in ECIG aerosols, but the effects of
      power, ECIG device design and liquid composition on ROS are relatively unknown.
      In addition, ROS emissions have not been examined in the emerging high power, sub
      Ohm device (SOD) category. In this study, an acellular 2',7'-dichlorofluorescin
      (DCFH) probe technique was optimized to measure ROS in ECIG aerosols. The
      technique was deployed to measure ROS emissions in SOD and supra-Ohm ECIGs while
      varying power, heater coil head design and liquid composition (PG/VG ratio and
      nicotine concentration). Liquids were made from analytical standards of PG, VG
      and nicotine and contained no flavorants. At high powers, ROS emissions in ECIGs
      and combustible cigarettes were similar. Across device designs, ROS emissions
      were uncorrelated with power (R2 = 0.261) but were highly correlated with power
      per unit area (R2 = 0.78). It was noticed that an increase in the VG percentage
      in the liquid yielded higher ROS flux, and nicotine did not affect ROS emissions.
      ROS emissions are a function of device design and liquid composition at a given
      power. For a given liquid composition, a promising metric for predicting ROS
      emissions across device designs and operating conditions is power per unit area
      of the heating coil. Importantly, ROS formation is significant even when the ECIG
      liquid consists of pure analytical solutions of PG and VG; it can therefore be
      viewed as intrinsic to ECIG operation and not solely a by-product of particular
      flavorants, contaminants or additives.

PMID- 30192936
TI  - Letter to the Editor: "Decreased Serum 25-Hydroxyvitamin D in Aging Male Mice Is
      Associated With Reduced Hepatic Cyp2r1 Abundance".

PMID- 30192933
TI  - The metagenome of the female upper reproductive tract.
AB  - Background: The human uterus is traditionally believed to be sterile, while the
      vaginal microbiota plays an important role in fending off pathogens. Emerging
      evidence demonstrates the presence of bacteria beyond the vagina. However, a
      microbiome-wide metagenomic analysis characterizing the diverse microbial
      communities has been lacking. Results: We performed shotgun-sequencing of 52
      samples from the cervical canal and the peritoneal fluid of Chinese women of
      reproductive age using the Illumina platform. Direct annotation of sequencing
      reads identified the taxonomy of bacteria, archaea, fungi and viruses, confirming
      and extending the results from our previous study. We replicated our previous
      findings in another 24 samples from the vagina, the cervical canal, the uterus
      and the peritoneal fluid using the BGISEQ-500 platform revealing that
      microorganisms in the samples from the same individuals were largely shared in
      the entire reproductive tract. Human sequences made up more than 99% of the 20GB
      raw data. After filtering, vaginal microorganisms were well covered in the
      generated reproductive tract gene catalogue, while the more diverse upper
      reproductive tract microbiota would require greater depth of sequencing and more
      samples to meet the full coverage scale. Conclusions: We provide novel detailed
      data on the microbial composition of a largely unchartered body site, the female
      reproductive tract. Our results indicated the presence of an intra-individual
      continuum of microorganisms that gradually changed from the vagina to the
      peritoneal fluid. This study also provides a framework for understanding the
      implications of the composition and functional potential of the distinct
      microbial ecosystems of the female reproductive tract in relation to health and
      disease.

PMID- 30192937
TI  - Functional Characterization of Thyrostimulin in Amphioxus Suggests an Ancestral
      Origin of the TH Signaling Pathway.
AB  - Thyrostimulin, consisting of GpA2 and GpB5 subunits, has been identified in
      amphioxus, but to date, little is known about the roles of GPA2/GPB5-type hormone
      in this evolutionarily important animal. We showed here that amphioxus GpA2,
      GpB5, and TSH receptor (TSHR) represent the archetypes of vertebrate TSHalpha,
      TSHbeta, and TSHR, respectively, and both gpa2 and gpb5 were coexpressed in the
      Hatschek pit, a homolog of the vertebrate pituitary, in amphioxus. We also showed
      that recombinant amphioxus GpA2 and GpB5, like zebrafish TSHalpha and TSHbeta,
      bound to both amphioxus and zebrafish TSHR and that tethered amphioxus
      thyrostimulin activated both protein kinase A and protein kinase C pathways in
      the cells expressing amphioxus TSHR. Moreover, we demonstrated that recombinant
      amphioxus thyrostimulin induced the production of thyroid hormone (TH) T4.
      Because genuine TSH is absent in amphioxus and thyrostimulin is the only and sole
      glycoprotein hormone, our data likely provide evidence that amphioxus
      thyrostimulin is a functional glycoprotein hormone that plays a role as TSH does
      in vertebrates. The data also suggest that the TH signaling pathway evolved in
      the basal chordate more than 500 million years ago.

PMID- 30192938
TI  - Dilution of Urine Followed by Adulteration in an Attempt to Deceive the
      Laboratory.
AB  - Adulteration of samples submitted for toxicological analyses can present unique
      challenges to non-forensic clinical laboratories. With the number of overdose
      related deaths expected to surpass 60,000 in 2018, it is incumbent on all members
      of the healthcare team to be active participants in curbing opioid dependence and
      identifying prescription drug misuse and diversion. Recently published guidelines
      have sought to provide guidance to laboratories overseeing prescription drug
      monitoring programs. We present a case of sample adulteration in an attempt to
      conceal prescription non-compliance. The patient possessed only an active
      prescription for hydrocodone but on initial antibody-based screening the sample
      tested positive for benzodiazepines and oxycodone in addition to opiates. Active
      communication between the pain management clinic and the clinical laboratory
      alerted staff to conduct a more thorough investigation including sample validity
      testing, analyses of paired serum specimens by liquid chromatography tandem mass
      spectrometry. Analyses revealed the patient submitted a dilute urine specimen
      with a crushed hydrocodone pill inside in an attempt to hide prescription non
      compliance. Previous screenings had been consistent with the medication list
      raising the question of whether this was an isolated incident or the patient had
      simply been more successful in manipulating specimens in the past. This case
      highlights the need for good communication among all members of the healthcare
      team and the widespread implementation of specimen validity testing for any
      laboratory that receives samples from pain clinics.

PMID- 30192939
TI  - Mortality and adverse events with brand and generic clopidogrel in the Food and
      Drug Administration Adverse Event Reporting System (FAERS).
AB  - Background and Aim: Clopidogrel is commonly used even after expiring patents. The
      brand clopidogel (BC) was dealt by single company, while numerous manufacturers
      produce generic clopidogrel (GC). There are no convincing data to compare the
      safety of different formulations. Therefore, the data yielded from international,
      uniform, government-mandated registries may be useful. Methods and Results: We
      assessed primary causative adverse events (PCAE) after BC and GC in the US Food
      and Drug Administration (FDA) Adverse Event Reporting System (FAERS). The
      outcomes were divided into death, cardiac, thrombotic/embolic, hemorrhagic, and
      rash/dermal complications. These primary endpoints were then examined by
      proportional risk ratios (PRR) and Chi-square ((chi2). Among total FAERS (n =
      9,466,679) reports, overall BC (n = 88,863) cases were more common than after GC
      (n = 36,559). When triaged by PCAE role, BC (n = 18,328) was also more abundant
      than GC (n = 3,987). The reported death rates were more than doubled after BC
      (18.4% vs. 7.0%; PRR=0.38; 95%CI:0.32-0.43; chi2=369.7;p<0.0001) for total FAERS,
      and consistent for late 2010-2017 (17.6% vs. 7.0% PRR=0.40; 95%CI:0.37-0.45;
      chi2=286.2;p<0.004) PCAE cases. In contrast, GC trended to co-report more cardiac
      (14.6% vs.13.3%; PRR=1.12; 95%CI:1.0-1.25; chi2=3.5;p<0.06). The hemorrhagic
      (40.9% vs. 32.3%; PRR=1.45; 95%CI:1.33-1.57; chi2=75.8;p<0.0001), and rash/dermal
      (5.4% vs.4.6%; PRR=1.20; 95%CI:1.0-1.44; chi2=3.75;p<0.05) events were also more
      common for GC. Thrombotic/embolic events were reported equally (at 7.0%) after
      each formulation. Conclusion: The PCAE profiles differ with BC and GC in FAERS.
      While deaths reports were higher, the rates of cardiac, hemorrhagic, and skin
      complications were less common for BC. Despite expected reporting bias, this may
      indicate that the manufacturers of GC are reluctant to report deaths to the FDA.
      However, the overall adverse event profile suggests potentially better safety of
      BC over GC formulations.

PMID- 30192943
TI  - Erratum.

PMID- 30192941
TI  - Ximmer: a system for improving accuracy and consistency of CNV calling from exome
      data.
AB  - Background: While exome and targeted next-generation DNA sequencing are primarily
      used for detecting single nucleotide changes and small indels, detection of copy
      number variants (CNVs) can provide highly valuable additional information from
      the data. Although there are dozens of exome CNV detection methods available,
      these are often difficult to use, and accuracy varies unpredictably between and
      within datasets. Findings: We present Ximmer, a tool that supports an end-to-end
      process for evaluating, tuning, and running analysis methods for detection of
      CNVs in germline samples. Ximmer includes a simulation framework, implementations
      of several commonly used CNV detection methods, and a visualization and curation
      tool that together enable interactive exploration and quality control of CNV
      results. Using Ximmer, we comprehensively evaluate CNV detection on four datasets
      using five different detection methods. We show that application of Ximmer can
      improve accuracy and aid in quality control of CNV detection results. In
      addition, Ximmer can be used to run analyses and explore CNV results in exome
      data. Conclusions: Ximmer offers a comprehensive tool and method for applying and
      improving accuracy of CNV detection methods for exome data.

PMID- 30192942
TI  - Considering formulation characteristics when prescribing and dispensing medicinal
      products for children: a qualitative study among GPs and pharmacists.
AB  - Background: Finding appropriate medicinal product formulations and dosage forms
      for children can be challenging. Knowledge about considerations behind which
      medicinal product to prescribe or dispense for children is lacking. Objective: To
      explore considerations of formulation characteristics of medicinal products made
      by GPs when prescribing and by pharmacists when dispensing medicines for children
      0-6 years of age. Method: A qualitative study was performed by conducting three
      semi-structured focus groups with GPs and three with pharmacists, using nearly
      identical thematic interview guides. Analysis was performed using systematic text
      condensation. Results: Both GPs and pharmacists considered whether children and
      parents were willing and able to use medicinal products such as tablets and poor
      tasting liquids before prescribing and dispensing them. These considerations were
      commonly based on health care workers' prior experiences, although parents and
      sometimes children were asked about their experiences with solid formulations.
      For antibiotics, GPs primarily wanted to prescribe first-choice antibiotics
      according to guidelines. Parents' concerns about getting the child to take the
      medicinal product due to poor taste could lead to the prescription of second
      choice antibiotics. The pharmacists sometimes changed the prescribed formulation
      at parents' request but never changed the type of antibiotic without contacting
      the prescriber. Conclusion: Formulation characteristics strongly influenced which
      medicinal product children were prescribed and dispensed. Individualizing
      formulation choices for children through an increased collaboration between
      physicians, pharmacists and parents is suggested.

PMID- 30192944
TI  - Erratum to: "A Conservation Hatchery Population of Delta Smelt Shows Evidence of
      Genetic Adaptation to Captivity After 9 Generations."

PMID- 30192940
TI  - Comparative genomics and transcriptomics of Chrysolophus provide insights into
      the evolution of complex plumage coloration.
AB  - Background: As one of the most recognizable characteristics in birds, plumage
      color has a high impact on understanding the evolution and mechanisms of
      coloration. Feather and skin are ideal tissues to explore the genomics and
      complexity of color patterns in vertebrates. Two species of the genus
      Chrysolophus, golden pheasant (Chrysolophus pictus) and Lady Amherst's pheasant
      (Chrysolophus amherstiae), exhibit brilliant colors in their plumage, but with
      extreme phenotypic differences, making these two species great models to
      investigate plumage coloration mechanisms in birds. Results: We sequenced and
      assembled a genome of golden pheasant with high coverage and annotated 15,552
      protein-coding genes. The genome of Lady Amherst's pheasant is sequenced with low
      coverage. Based on the feather pigment identification, a series of genomic and
      transcriptomic comparisons were conducted to investigate the complex features of
      plumage coloration. By identifying the lineage-specific sequence variations in
      Chrysolophus and golden pheasant against different backgrounds, we found that
      four melanogenesis biosynthesis genes and some lipid-related genes might be
      candidate genomic factors for the evolution of melanin and carotenoid
      pigmentation, respectively. In addition, a study among 47 birds showed some
      candidate genes related to carotenoid coloration in a broad range of birds. The
      transcriptome data further reveal important regulators of the two colorations,
      particularly one splicing transcript of the microphthalmia-associated
      transcription factor gene for pheomelanin synthesis. Conclusions: Analysis of the
      golden pheasant and its sister pheasant genomes, as well as comparison with other
      avian genomes, are helpful to reveal the underlying regulation of their plumage
      coloration. The present study provides important genomic information and insights
      for further studies of avian plumage evolution and diversity.

PMID- 30192946
TI  - Evaluating the validity and reliability of the Medical Interview Satisfaction
      Scale in South African primary care consultations.
AB  - Background: Effective primary care is vital for improving health outcomes.
      Patient-centred consultations are important and one way of assessing this is to
      evaluate patient satisfaction. The Medical Interview Satisfaction Scale (MISS)
      has not been used in South Africa. Aim: To test validity and reliability of the
      MISS and evaluate patient satisfaction with consultations. Setting: Primary care
      facilities in the Helderberg sub-district, South Africa. Methods: The MISS tool
      was adapted and validated by a panel of experts. The internal consistency was
      evaluated on 150 consultations. The level of patient satisfaction on 23 items, in
      consultations by nurses and doctors, was measured. Respondents indicated
      agreement with each item on a scale (1 = very strongly disagree, 7 = very
      strongly agree). Results: The wording of the items were adapted and translated
      into Afrikaans and Xhosa. There was good overall internal consistency (Cronbach
      alpha 0.889), but not in all subscales. Patients were most satisfied with rapport
      (Median score 6.2 (IQR 5.3-5.9)) and understanding of their concerns, fears and
      beliefs (5.7 (IQR 5.1-6.3)). They were less satisfied with the ability to foster
      an acceptable management plan (5.5 (IQR 4.5-6.5)) and with accuracy of
      information (5.0 (IQR 4.2-5.8)). Scores for nurses and doctors were not
      significantly different. Conclusion: Further work is needed to improve the
      reliability of MISS subscales in the South African context and the best internal
      consistency was found with 21 items. Patients showed high levels of satisfaction
      with primary care consultations, although other studies suggest this may reflect
      low expectations rather than high quality consultations.

PMID- 30192945
TI  - Metabolomics investigation of dietary effects on flesh quality in grass carp
      (Ctenopharyngodon idellus).
AB  - Background: The ultrahigh density intensive farming model of grass carp
      (Ctenopharyngodon idellus) may elicit growth inhibition, decrease flesh quality,
      and increase disease susceptibility of fish. The degradation in quality and
      excessive fat accumulation in cultured C. idellus have long been attributed to
      possible alterations in the lipid metabolism of fish muscle tissues as a result
      of overnutrition from artificial diets. To investigate the effects of different
      diets on fish muscle quality, a large-scale metabolomics study was performed on
      250 tails of C. idellus. Findings: The experimental fish were divided into four
      groups based on sex and diet-female artificial feed (FAF), female grass feed,
      male artificial feed (MAF), and male grass feed (MGF). After a 113-day rearing
      period, the artificial feed (AF) group showed a significantly higher total mass
      of muscle fat (P < 0.01), with the FAF group being the highest. Metabolomics
      profiling based on liquid chromatography-mass spectrometry revealed distinctive
      patterns of clustering according to the four groups. Overall, artificial feeding
      was associated with higher concentrations of docosapentaenoic acid, dihomo-gamma
      linolenic acid, and arachidonic acid, whereas grass feeding was associated with
      elevated n-3 unsaturated fatty acids (UFAs) such as eicosapentaenoic acid, alpha
      linolenic acid, and gamma-linolenic acid. Artificial feeding also resulted in
      significant increased docosahexaenoic acid in MAF muscle than in MGF fish,
      whereas there was no significance in the comparison of female samples. Metabolic
      pathway analyses using both targeted and untargeted approaches consistently
      revealed that arachidonic acid metabolism and steroid hormone biosynthesis
      pathways were significantly different between AF and grass fed groups.
      Conclusions: Our results suggest that grass is a better source of dietary fatty
      acid and protein when compared to artificial feed. Grass feeding could
      effectively lower triglycerides in serum, reduce fat accumulation, and alter
      lipid compositions in fish muscle by increasing the concentrations of n-3 UFAs,
      leading to better nutrition and health.

PMID- 30192947
TI  - Information-seeking, information sources and ongoing support needs after
      discharge to prevent cancer-related lymphoedema.
AB  - Objectives: To compare gynaecological and breast cancer patients in their
      information-seeking behaviours, usefulness of information sources and ongoing
      care needs after discharge to prevent the onset of lymphoedema. Methods: We
      conducted a consecutive cross-sectional survey in an oncology hospital. Adult
      patients with stage I, II or III gynaecological or breast cancer who had
      undergone lymph node dissection and had not been diagnosed with lymphoedema were
      eligible for inclusion. The survey explored physical health status, knowledge of
      self-care, information-seeking behaviours, information sources and need for
      ongoing care from an oncology hospital and/or community health centre. Results:
      Among 254 patients recruited, 202 responded (79.5% response rate). In total, 147
      patients were eligible for statistical analysis. Irrespective of cancer type, the
      most commonly sought information was lymph drainage. Information on preventing
      weight gain was sought more often by breast cancer patients than gynaecological
      cancer patients. Regardless of cancer type, the most common information sources
      were nurses at an oncology hospital. Gynaecological cancer patients perceived
      nurses at the oncology hospital as useful for understanding risks, symptoms and
      prevention of lymphoedema. Irrespective of cancer type, ongoing need for help
      with lymphoedema prevention was reported both from the oncology hospital and the
      community centre. Limb symptoms, poor health status and poor knowledge affected
      the ongoing needs of gynaecological cancer patients at the oncology hospital,
      whereas poor health status affected ongoing needs in community health centres
      among both types of cancer patients. Conclusions: Both gynaecological and breast
      cancer patients reported ongoing care needs, but that details of information
      seeking behaviours differed.

PMID- 30192948
TI  - Personal Projects and Psychological Well-Being: Emerging Adults With and Without
      Diabetes.
AB  - Objective: The goal of this study was to examine the nature of the personal
      projects that emerging adults with and without diabetes were pursuing and the
      implications of those projects for psychological well-being. Methods: We asked
      emerging adults with and without type 1 diabetes to identify five personal
      projects, rate four dimensions of those projects (importance, typicality, stress,
      and progress), and complete several well-being measures (depressive symptoms,
      life purpose, life satisfaction, perceived stress, and resilience) when they were
      age 19. Those with diabetes also indicated the extent to which diabetes
      interfered with each of the projects. We followed participants for 1 year to
      determine the status of projects and reassess project dimensions and
      psychological well-being. Results: The kinds of projects identified by the two
      groups were similar. However, those with diabetes reported lower levels of
      progress on projects and completed fewer projects 1 year later compared with
      controls. Project progress, importance, and completion were linked to higher
      psychological well-being, whereas project stress was linked to lower
      psychological well-being. However, the most robust cross-sectional and
      longitudinal predictor of psychological well-being was project typicality (i.e.,
      the extent to which projects were typical of participants). The pursuit of more
      typical projects was linked to higher psychological well-being. These findings
      were largely similar for emerging adults with and without diabetes. Diabetes
      interference with projects revealed some links to psychological well-being.
      Conclusions: These results suggest that personal project engagement and
      completion is linked to the overall mental health of emerging adults with and
      without diabetes.

PMID- 30192949
TI  - Cytokine Profiles and Severity of Influenza Infection in Transplant Recipients.
AB  - Influenza is responsible for significant morbidity after transplantation. We
      evaluated Th1/Th2 cytokines and IL-10 levels during influenza infection in the
      post-transplant setting. Sera from 277 transplant recipients were analyzed at
      influenza diagnosis and 28 days later for IFN-gamma, IL-4, IL-13 and IL-10. IL-13
      levels were associated with protection against pneumonia and ICU admission,
      whereas the IFN-gamma/IL-13 ratio and IL-10 levels were associated with an
      increased risk of pneumonia and ICU admission. This association was independent
      of viral load. A skewing of immune responses towards Th2 in transplant patients
      appears to confer protection from severe influenza infection, independently of
      viral load.

PMID- 30192950
TI  - Sequential cleavage of the proteins encoded by HNOT/ALG3, the human counterpart
      of the Drosophila NOT and yeast ALG3 gene, results in products acting in distinct
      cellular compartments.
AB  - This study provides first insights into the biosynthesis, structure, biochemistry
      and complex processing of the proteins encoded by hNOT/ALG3, the human
      counterpart of the Drosophila Neighbour of TID (NOT) and the yeast asparagine
      linked glycosylation 3 gene (ALG3), which encodes a mannosyltransferase.
      Unambiguous evidence that both the fly and human proteins act as
      mannosyltransferases has not been provided yet. Previously, we showed that
      hNOT/ALG3 encodes two alternatively spliced main transcripts, hNOT-1/ALG3-1 and
      hNOT-4/ALG3-4, and their 15 truncated derivatives that lack diverse sets of exons
      and/or carry point mutations that result in premature termination codons. Here we
      show that the truncated transcripts are not translated. The two main forms hNOT
      1/ALG3-1 and -4, distinguishable by alternative exon 1, encode full-length
      precursors that undergo a complex posttranslational processing. To specifically
      detect the two full-length hNOT/ALG3 proteins and their distinct derivatives and
      to examine their expression profiles and cellular location we generated
      polyclonal antibodies against diverse parts of the putative full-length proteins.
      We provide experimental evidence for the N-glycosylation of the two precursors.
      This modification seems to be a prerequisite for their sequential cleavage
      resulting in derivatives destined to distinct cellular compartments and links
      them with the N-glycosylation machinery not as its functional component but as
      molecules functionally dependent on its action. We present the expression
      profiles and subcellular location of the two full-length proteins, their N
      glycosylated forms and distinct cleavage products. Furthermore, using diverse
      bioinformatics tools, we characterize the properties and predict the 2D and 3D
      structure of the two proteins and, for comparative purposes, of their Drosophila
      counterpart.

PMID- 30192952
TI  - Effectiveness of Boric Acid by Ingestion, But Not by Contact, Against the Common
      Bed Bug (Hemiptera: Cimicidae).
AB  - Boric acid has been used as an insecticide in the successful control of
      agricultural, public health and urban pests long before the advent of synthetic
      organic pesticides. Boric acid products, formulated as dusts, sprays, granular
      baits, pastes, gels, and liquids, are widely available to consumers and pest
      management professionals, especially to control pest infestations within homes.
      Boric acid dust is commonly used against bed bugs (Cimex lectularius L.
      [Hemiptera: Cimicidae]), but its efficacy has not been demonstrated. We evaluated
      the efficacy of boric acid as an ingestible and residual contact insecticide on
      bed bugs, and compared its efficacy on the German cockroach (Blattella germanica
      L. [Blattodea: Ectobiidae]) which is known to be susceptible to boric acid by
      both routes. Dose-response studies of 0-5% boric acid in blood demonstrated that
      ingested boric acid caused rapid mortality at concentrations of >=2%, and even
      0.5% and 1% boric acid caused 100% mortality, albeit at a slower time course. In
      contrast, bed bugs survived contact with high concentrations of boric acid dust.
      Smaller boric acid particles did not increase mortality of either unfed or
      recently fed bed bugs. The same boric acid products were effective at causing
      mortality of German cockroaches by both contact and ingestion. We thus conclude
      that although boric acid is an excellent candidate active ingredient for an
      ingestible bait formulation, residual applications of dust or spray would be
      ineffective in bed bug interventions.

PMID- 30192951
TI  - Sequana coverage: detection and characterization of genomic variations using
      running median and mixture models.
AB  - Background: In addition to mapping quality information, the Genome coverage
      contains valuable biological information such as the presence of repetitive
      regions, deleted genes, or copy number variations (CNVs). It is essential to take
      into consideration atypical regions, trends (e.g., origin of replication), or
      known and unknown biases that influence coverage. It is also important that
      reported events have robust statistics (e.g. z-score) associated with their
      detections as well as precise location. Results: We provide a stand-alone
      application, sequana_coverage, that reports genomic regions of interest (ROIs)
      that are significantly over- or underrepresented in high-throughput sequencing
      data. Significance is associated with the events as well as characteristics such
      as length of the regions. The algorithm first detrends the data using an
      efficient running median algorithm. It then estimates the distribution of the
      normalized genome coverage with a Gaussian mixture model. Finally, a z-score
      statistic is assigned to each base position and used to separate the central
      distribution from the ROIs (i.e., under- and overcovered regions). A double
      thresholds mechanism is used to cluster the genomic ROIs. HTML reports provide a
      summary with interactive visual representations of the genomic ROIs with standard
      plots and metrics. Genomic variations such as single-nucleotide variants or CNVs
      can be effectively identified at the same time.

PMID- 30192953
TI  - Where Animation and Science Meet.
AB  - SYNOPSIS: Animation is the collision of art and science. How does an animation
      studio like DreamWorks Animation use scientific principles and engage in science
      education to make our films better? By facilitating scientific master-classes,
      demos, and lectures we give our creators a fundamental understanding of reality
      that enables them to create the animation caricature known as the Illusion of
      Life. We leverage principles of biology and physics to create believable
      performances. I will share insights about our custom programming such as master
      classes on Quadruped Anatomy and Flight and how these result in a better image on
      screen. Conversely, animators offer storytelling tools to the scientific
      community. Animators often use visualization tools similar to those that many
      scientists use, but in differing narrative orders and with budgets often far
      exceeding those of scientists. I will highlight strategies of presentation
      enhancing understanding and increasing the speed of building bridges to share
      information with the public. This can help scientists leverage their own
      scientific principles as they present the importance and excitement of their work
      to the public, as well as to one another.

PMID- 30192954
TI  - The Burden of Human Papillomavirus and Chlamydia trachomatis Coinfection in
      Women: A Large Cohort Study in Inner Mongolia, China.
AB  - Background: Chlamydia trachomatis may coinfect with human papillomavirus (HPV)
      and complicate the cervical pathogenesis. This study aimed to evaluate the
      prevalence, risk factors, and clinical outcomes of HPV/C. trachomatis coinfection
      in women from Inner Mongolia, China. Methods: We performed a polymerase chain
      reaction (PCR)-based HPV/C. trachomatis screening and cervical samples were
      analyzed by thinprep cytologic test. Statistical analysis was used to assess the
      association between demographic factors and coinfection. Results: Among the 2345
      women recruited, the prevalences of HPV, C. trachomatis, and HPV/C. trachomatis
      coinfection were 36.0%, 14.3%, and 4.8%, respectively. The rate of multiple HPV
      genotypes was higher in coinfected women. HPV66 was the most frequently
      identified genotype in coinfected participants. The HPV DNA load was
      significantly higher in HPV monoinfected cases. In contrast, the DNA load of C.
      trachomatis was significantly higher in the coinfection group. Risk factors,
      including single women (odds ratio [OR] = 6.0, 95% confidence interval [CI],
      4.044-8.782) and women with multiple sex partners (OR = 1.9, 95% CI, 1.324
      2.824), were associated with coinfection. Importantly, coinfection was associated
      with increased risk for high-grade squamous intraepithelial lesions. Conclusions:
      HPV and C. trachomatis coinfection is an important risk factor for the
      progression of cervical lesions.

PMID- 30192955
TI  - PREHISTORIC BODY THEATER: bringing paleontology narratives to global contemporary
      performance audiences.

PMID- 30192956
TI  - Evaluation of a sheep rumen model with fresh forages of diverse chemical
      composition.
AB  - The sheep rumen submodel MollyRum14 was evaluated on its methane and VFA
      predictions against data from respiration-chamber trials conducted with sheep fed
      perennial ryegrass, white clover, chicory, forage rape, turnip (leafy and bulb
      varieties), swedes, kale, or forage radish. We assessed the model's response to
      substrate degradation rate (settings that affect the rate of cellulose and
      hemicellulose digestion) and to fermentation stoichiometry (settings that alter
      nonglucogenic to glucogenic short-chain fatty acid ratios). Model predictions
      were evaluated against data for methane production (pCH4: g/d), methane yield
      (yCH4: g/kg DMI), and acetate to propionate ratio (A:P). The predictive ability
      of the model for both pCH4 and yCH4 was superior for perennial ryegrass than for
      other forages. Except for swedes and chicory, predictions for yCH4 were correctly
      ranked across the forages evaluated. Except for forage rape, robust predictions
      were obtained for all forages using fast degradation kinetics and a predominantly
      acetogenic stoichiometry. Model predictions for forage rape were enhanced using
      slow degradation kinetics and a predominantly propionic stoichiometry. These
      results indicate that MollyRum14 is suitable to predict methane emissions from
      sheep fed a variety of fresh forages including annual fodder crops. However, a
      clear understanding of degradation rates and stoichiometries is needed to enhance
      the utility of the model as a predictive tool. This would allow continuous
      adjustment of digestion rates and stoichiometries to be potentially tailored to
      individual forage species.

PMID- 30192957
TI  - Determination of Antiepileptic Drugs Using Dried Saliva Spots.
AB  - The present work describes the development and validation of an analytical method
      for the determination of the antiepileptic drugs (AEDs) phenytoin, phenobarbital,
      carbamazepine and its active metabolite carbamazepine-10,11-epoxide, in oral
      fluid using liquid chromatography coupled to a diode array detector. Correlation
      between plasma and oral fluid for these compounds has been proven before, making
      this matrix a great non-invasive alternative for drug-monitoring purposes. The
      adaptation of cards, commonly applied in dried blood spots (DBS) sampling, to
      oral fluid resulted in dried saliva spots (DSS). The extraction procedure
      consisted of applying 50 MUL of oral fluid to WhatmanTM 903 protein saver cards
      and drying for 1 h. The extraction was performed with 1 mL of acidified methanol
      (pH = 5.5) for 5 min with agitation. Afterward, the sample was centrifuged for 15
      min at 3,500 rpm and the supernatant was evaporated and reconstituted with 80 MUL
      of mobile phase. For the AEDs separation, a Zorbax SB-C18 column (1.8 MUm, 4.6 *
      250 mm i.d.) maintained at 35 degrees C was used, and the mobile phase consisted
      of 35% acetonitrile and 65% of water:methanol:triethylamine (75.5%:24.2%:0.3%)
      isocratically with a flow of 0.5 mL/min, and the wavelength was monitored at 210
      nm. The method was validated according to internationally accepted criteria, and
      linearity between 0.1-10 MUg/mL was obtained for all AEDs. This is the first
      method using DSS for the determination of AEDs, showing great potential for
      routine use in a laboratory for its simplicity, in addition to the advantages
      inherent to the use of oral fluid as a sample.

PMID- 30192959
TI  - Commentary: An Important Problem but a "Probably Don't Do It" Solution.

PMID- 30192958
TI  - Prevalence and correlates of obstructive sleep apnea among African Americans: the
      Jackson Heart Sleep Study.
AB  - Study Objectives: African Americans have been under-represented in obstructive
      sleep apnea (OSA) research. This study determined the prevalence and correlates
      of OSA overall and by sex among African Americans in the Jackson Heart Sleep
      Study. Methods: Participants (N = 852) underwent a type 3 in-home sleep apnea
      study, 7 day wrist actigraphy and completed standardized measurements and
      questionnaires. OSA was defined as an apnea-hypopnea index (AHI) of >=15, where
      hypopneas were defined as >= 4% associated desaturation. Physician diagnosis of
      OSA was self-reported. Logistic regression models were fit to determine the
      associations of demographics, socioeconomic status, sleep symptoms, actigraphy
      based sleep, body mass index (BMI), and comorbidities with OSA. Results: Average
      age was 63.1 (standard deviation = 10.7), 66% were female, and mean BMI was 32.0
      (6.9) kg/m2. Approximately 24% had an AHI >= 15; of those, 5% had a physician
      diagnosis of OSA. Prevalence of OSA increased across BMI categories, but not age
      groups. Men had a 12% higher prevalence of OSA compared with women, p < 0.01.
      Older age, male sex, higher BMI, larger neck circumference, and report of
      habitual snoring were independently associated with higher odds of OSA, all p <
      0.05. Associations between sleep symptoms and OSA were similar for men and women.
      Sleepiness and waist circumference were not associated with OSA. Conclusions:
      There was a high prevalence of objectively measured but undiagnosed OSA in this
      sample of African Americans. Snoring, BMI, and neck circumference were important
      markers of OSA for men and women. Our results suggest that screening tools that
      incorporate information on sleepiness and waist circumference may be suboptimal
      in this population.

PMID- 30192961
TI  - Aberrant Stamen Development is Associated with Parthenocarpic Fruit Set through
      Up-regulation of Gibberellin Biosynthesis in Tomato.
AB  - Parthenocarpy, a process in which fruit set occurs without fertilization, leads
      to the production of seedless fruit. A number of floral homeotic mutants with
      abnormal stamen development exhibit parthenocarpic fruit set. Flower development
      is thought to repress ovary growth before anthesis. However, the mechanism of
      parthenocarpic fruit development caused by aberrant flower formation is poorly
      understood. To investigate the molecular mechanism of parthenocarpic fruit
      development in floral homeotic mutants, we performed functional analysis of
      Tomato APETALA3 (TAP3) by loss-of-function approaches. Organ-specific promoter
      was used to induce organ-specific loss of function in stamen and ovary/fruit. We
      observed increased cell expansion in tap3 mutants and TAP3-RNAi lines during
      parthenocarpic fruit growth. These were predominantly accompanied by the up
      regulation of GA biosynthesis genes, including SlGA20ox1, SlGA20ox2, and
      SlGA20ox3, as well as reduced expression of the GA-inactivating gene SlGA2ox1 and
      the auxin signaling gene SlARF7 involved in a crosstalk between GA and auxin.
      These transcriptional profiles are in agreement with the GA levels in these
      lines. These results suggest that stamen development negatively regulates fruit
      set by repressing the GA biosynthesis.

PMID- 30192960
TI  - Medium-Chain Polyprenols Influence Chloroplast Membrane Dynamics in Solanum
      lycopersicum.
AB  - The widespread occurrence of polyprenols throughout the plant kingdom is well
      documented, yet their functional role is poorly understood. These lipophilic
      compounds are known to be assembled from isoprenoid precursors by a class of
      enzymes designated as cis-prenyltransferases (CPTs), which are encoded by small
      CPT gene families in plants. In this study, we report that RNA interference
      (RNAi)-mediated knockdown of one member of the tomato CPT family (SlCPT5) reduced
      polyprenols in leaves by about 70%. Assays with recombinant SlCPT5 produced in
      Escherichia coli determined that the enzyme synthesizes polyprenols of
      approximately 50-55 carbons (Pren-10, Pren-11) in length and accommodates a
      variety of trans-prenyldiphosphate precursors as substrates. Introduction of
      SlCPT5 into the polyprenol-deficient yeast Deltarer2 mutant resulted in the
      accumulation of Pren-11 in yeast cells, restored proper protein N-glycosylation
      and rescued the temperature-sensitive growth phenotype that is associated with
      its polyprenol deficiency. Subcellular fractionation studies together with in
      vivo localization of SlCPT5 fluorescent protein fusions demonstrated that SlCPT5
      resides in the chloroplast stroma and that its enzymatic products accumulate in
      both thylakoid and envelope membranes. Transmission electron microscopy images of
      polyprenol-deficient leaves revealed alterations in chloroplast ultrastructure,
      and anisotropy measurements revealed a more disordered state of their envelope
      membranes. In polyprenol-deficient leaves, CO2 assimilation was hindered and
      their thylakoid membranes exhibited lower phase transition temperatures and
      calorimetric enthalpies, which coincided with a decreased photosynthetic electron
      transport rate. Taken together, these results uncover a role for polyprenols in
      governing chloroplast membrane dynamics.

PMID- 30192962
TI  - Percutaneous Transvenous Glue Embolization of a Large Mandibular Arteriovenous
      Malformation: Neuroendovascular 2-Dimensional Operative Video.

PMID- 30192963
TI  - Nicotine dependence among adolescents in the European Union: How many and who are
      affected?
AB  - Background: Nicotine dependence during adolescence increases the risk of
      continuing smoking into adulthood. The magnitude of nicotine dependence among
      adolescents in the European Union (EU) has not been established. We aimed to
      estimate the number of nicotine dependent 15-year-old adolescents in the EU, and
      identify high-risk groups. Methods: The number of nicotine dependent 15-year-olds
      in the EU was derived combining: (i) total number of 15-year-olds in the EU (2013
      Eurostat), (ii) smoking prevalence among 15-year-olds (2013/2014 HBSC survey) and
      (iii) proportion of nicotine dependent 15-year-olds in six EU countries (2013
      SILNE survey). Logistic regression analyses identified high-risk groups in the
      SILNE dataset. Results: We estimated 172 636 15-year-olds were moderately to
      highly nicotine dependent (3.2% of all 15 years old; 35.3% of daily smokers). In
      the total population, risk of nicotine dependence was higher in males,
      adolescents with poor academic achievement, and those with smoking parents or
      friends. Among daily smokers, only lower academic achievement and younger age of
      smoking onset were associated with nicotine dependence. Conclusion: According to
      our conservative estimates, more than 172 000 15-year-old EU adolescents were
      nicotine dependent in 2013. Prevention of smoking initiation, especially among
      adolescents with poor academic performance, is necessary to prevent a similar
      number of adolescents getting addicted to nicotine each consecutive year.

PMID- 30192964
TI  - Tobacco harm reduction: Making sure no one gets left behind.

PMID- 30192965
TI  - Clustering of behavioural risk factors for health in UK adults in 2016: a cross
      sectional survey.
AB  - Background: Foods high in fat, sugar and salt (HFSS) are known to contribute to
      overweight and obesity. In addition to overweight and obesity, smoking, alcohol
      consumption and physical inactivity are known risk factors for non-communicable
      diseases, including several cancers and cardiovascular disease. Methods:
      Secondary analysis of UK-representative cross-sectional survey data of 3293
      adults aged 18+. Regression analyses were undertaken to understand the
      relationship between consumption of HFSS food and soft drinks, alcohol and
      tobacco and socio-demographics. Clustering analysis identified groupings of
      health risk factors. Results: Males, those aged 18-24 and those from the more
      deprived groups consumed ready meals and fast food most frequently. Most of the
      sample (77.3%) engaged in at least one health risk behaviour. Six clusters were
      identified in the clustering analysis. Older (65+) female respondents were more
      likely to be inactive. Smokers exhibiting additional risk behaviours were more
      likely to be of working age from more deprived groups, and men over 65 were more
      likely to consume harmful levels of alcohol with additional risk factors.
      Conclusion: Policies and services in the UK tend to focus on changing behaviour
      to address individual risk factors. This study shows that policies and
      interventions need to address multiple risk factors.

PMID- 30192966
TI  - Characteristics of Bilirubin According to the Results of the Direct Antiglobulin
      Test and Its Impact in Hemolytic Disease of the Newborn.
AB  - Background: Hyperbilirubinemia, which is a sign of hemolytic disease of the
      newborn (HDN), can irreversibly damage the central nervous system. Objectives: To
      determine the etiology of HDN in affected patients and characterize the changing
      pattern of bilirubin using direct antiglobulin testing (DAT). Methods: We
      collected clinical data from newborns who underwent perinatal DAT and from their
      mothers, between August 2008 and July 2017. Results: Among 303 neonates, 37
      (12.2%) showed positive DAT results. The positive predictive values (PPVs) and
      negative predictive values (NPVs) based on DAT results were 75.7% and 28.9%,
      respectively, for starting phototherapy. Bilirubin levels increased more rapidly
      in the DAT-positive group, compared with the DAT-negative group. The initial
      bilirubin level differed significantly according to the etiology of
      hyperbilirubinemia. Further, neonates with anti-D showed higher delta bilirubin
      per day than neonates with other antibodies. Conclusion: Our results may help to
      determine the measurement period for bilirubin according to DAT results and
      etiology.

PMID- 30192967
TI  - Uncoiling CNLs: Structure/function approaches to understanding CC domain function
      in plant NLRs.
AB  - Plant NLRs are intracellular pathogen receptors whose N-terminal domains are
      integral to signal transduction after perception of a pathogen-derived effector
      proteins. The two major plant NLR classes are defined by the presence of either a
      TIR or CC domain at their N-terminus (TNLs and CNLs). Our knowledge of how CC
      domains function in plant CNLs lags behind that of how TIR domains function in
      plant TNLs. CNLs are the most abundant class of NLRs in monocotyledonous plants,
      and further research is required to understand the molecular mechanisms of how
      these domains contribute to disease resistance in cereal crops. Previous studies
      of CC domains have revealed functional diversity, making categorisation
      difficult, which in turn makes experimental design for assaying function
      challenging. In this review, we summarise the current understanding of CC domain
      function in plant CNLs, highlighting the differences in modes of action and
      structure. To aid experimental design in exploring CC domain function, we present
      a "best-practice" guide to designing constructs through use of sequence and
      secondary structure comparisons and discuss the relevant assays for investigating
      CC domain function. Finally, we discuss whether using homology modelling is
      useful to describe putative CC domain function in CNLs through parallels with the
      functions of previously characterised helical adaptor proteins.

PMID- 30192969
TI  - Timely recognition of hematophagocytosis attributable to coexistence of lymphoma
      and tuberculosis.

PMID- 30192968
TI  - Meningitis by Streptococcus agalactiae secondary to otitis media.

PMID- 30192970
TI  - Dental health is a neglected topic in travel medicine.

PMID- 30192971
TI  - Dysphagia aortica.

PMID- 30192973
TI  - GhTCP19 transcription factor regulates corm dormancy release by repressing GhNCED
      expression in Gladiolus.
AB  - Dormancy is one of the least understood phenomena in plant biology, however
      bud/corm dormancy is an important economic trait in agricultural/horticultural
      breeding. In this study, we isolated an abscisic acid (ABA) biosynthesis gene,
      GhNCED, from the transcriptome database of corm dormancy release (CDR), and
      characterized its negative role in regulating CDR. To understand transcriptional
      regulation of GhNCED, yeast one-hybrid screening was conducted and GhTCP19 was
      identified and shown to directly regulate GhNCED expression. In planta assay
      showed that GhTCP19 negatively regulates GhNCED expression. GhTCP19 is
      dramatically induced by exogenous cytokinins (CK) and is induced during CDR.
      Silencing of GhTCP19 in dormant cormels delayed CDR, resulting in higher
      expression of GhNCED and ABA levels. Meanwhile, endogenous CK biosynthesis and
      signaling were inhibited in GhTCP19-silenced cormels. Taken together, our results
      reveal that GhTCP19 is a positive regulator of the CDR process by repressing an
      ABA biosynthesis gene's expression (GhNCED) and promoting CK biosynthesis
      (GhIPT), signal transduction (GhARR), as well as cyclin genes. This study expands
      our knowledge on corm dormancy release which is mediated by TCP family members.

PMID- 30192972
TI  - Infectious disease implications of large-scale migration of Venezuelan nationals.
AB  - Background: The ongoing economic and political crisis in Venezuela has resulted
      in a collapse of the healthcare system and the re-emergence of previously
      controlled or eliminated infectious diseases. There has also been an exodus of
      Venezuelan international migrants in response to the crisis. We sought to
      describe the infectious disease risks faced by Venezuelan nationals and assess
      the international mobility patterns of the migrant population. Methods: We
      synthesized data on recent infectious disease events in Venezuela and among
      international migrants from Venezuela, as well as on current country of residence
      among the migrant population. We used passenger-level itinerary data from the
      International Air Transport Association to evaluate trends in outbound air travel
      from Venezuela over time. We used two parameter-free mobility models, the
      radiation and impedance models, to estimate the expected population flows from
      Venezuelan cities to other major Latin American and Caribbean cities. Results:
      Outbreaks of measles, diphtheria and malaria have been reported across Venezuela
      and other diseases, such as HIV and tuberculosis, are resurgent. Changes in
      migration in response to the crisis are apparent, with an increase in Venezuelan
      nationals living abroad, despite an overall decline in the number of outbound air
      passengers. The two models predicted different mobility patterns, but both
      highlighted the importance of Colombian cities as destinations for migrants and
      also showed that some migrants are expected to travel large distances. Despite
      the large distances that migrants may travel internationally, outbreaks
      associated with Venezuelan migrants have occurred primarily in countries
      proximate to Venezuela. Conclusions: Understanding where international migrants
      are relocating is critical, given the association between human mobility and the
      spread of infectious diseases. In data-limited situations, simple models can be
      useful for providing insights into population mobility and may help identify
      areas likely to receive a large number of migrants.

PMID- 30192974
TI  - Altitudinal Turnover of Species in a Neotropical Peripheral Mountain System: A
      Case Study With Dung Beetles (Coleoptera: Aphodiinae and Scarabaeinae).
AB  - The study of diversity gradients is a frequent approach to understand
      evolutionary processes that structure communities. Altitudinal gradients allow
      the analysis of community spatial responses to environmental fluctuations. One
      interesting place to study altitudinal gradients is the Andes system because of
      the coexistence of isolated and continuous mountain ranges. We investigated the
      altitudinal turnover of species in peripheral mountainous systems by analyzing
      the structure of dung beetle assemblages along a complete gradient in the Sierra
      Nevada de Santa Marta, Colombia. Seven sites ranging from 480 to 2,890 m were
      evaluated, using linear transects of pitfall traps. A total of 2,992 individuals
      and 46 species were collected. Abundance, richness, and diversity diminished with
      altitude, revealing significant differences among sites. Some genera appeared at
      certain altitudes and most species appeared at unique sites, indicating a marked
      altitudinal turnover. A similarity analysis demonstrated the existence of
      separate lowland and high mountain groups with a turnover at 1,200-1,600 m asl.
      We registered for the first time a species replacement between Scarabaeinae (low
      lands) and Aphodiinae (high-lands) in the Neotropical region. Our results largely
      agree with the species pattern described for Mesoamerica, although, in this case
      the altitudinal turnover is more evident, unveiling a transition zone between
      lowland and high mountain fauna elements. This result suggests an equilibrium
      between a weak horizontal colonization and a strong vertical turnover, that
      appears to be higher in isolated mountains. Future investigations with other
      insect groups are necessary to corroborate this altitudinal pattern in isolated
      mountains.

PMID- 30192976
TI  - Work ability meetings-a survey of Finnish occupational physicians.
AB  - Background: Work ability meetings (WAMs) are planned discussions between an
      employee, a manager and an occupational physician (OP) to support work ability
      and return to work (RTW). During the last decade, WAMs become a popular
      intervention in Finnish occupational healthcare, although research on their
      content is lacking. Aims: To describe the practice of WAMs in Finland. Methods:
      We sent an internet survey by e-mail to members of the Finnish Society of
      Occupational Health Physicians in August 2014. We asked them to describe the last
      WAM they had attended, the employee the meeting concerned, the reason why it was
      convened, the content of the meeting and the action plan developed. Results: A
      total of 303 of 1304 OPs responded (24%) to the survey. The meetings were most
      often arranged for employees in manual or clerical work (71%). There were several
      overlapping reasons for convening a WAM, including a worker's reduced work
      ability (57%), functional ability (42%) or long-term sickness absence (38%). The
      meetings consisted of RTW planning, clarification of the situation and a dialogue
      between the three parties. In half of the cases, the action plans dealt with
      modifications of work tasks. A third of cases were forwarded to vocational
      rehabilitation, while permanent disability pension was considered in 6% of cases.
      Conclusions: The focus of WAMs was on workplace adjustments to support workers to
      remain at work. The WAMs dealt mostly with early interventions for RTW: work
      modifications, adjustments and vocational rehabilitation.

PMID- 30192975
TI  - Natural History and Pathogenesis of Wild-Type Marburg Virus Infection in STAT2
      Knockout Hamsters.
AB  - Marburg virus (MARV; family Filoviridae) causes sporadic outbreaks of Marburg
      hemorrhagic fever in sub-Saharan Africa with case fatality rates reaching 90%.
      Wild-type filoviruses, including MARV and the closely related Ebola virus, are
      unable to suppress the type I interferon response in rodents, and therefore
      require adaptation of the viruses to cause disease in immunocompetent animals. In
      the current study, we demonstrate that STAT2 knockout Syrian hamsters are
      susceptible to infection with different wild-type MARV variants. MARV Musoke
      causes a robust and systemic infection resulting in lethal disease.
      Histopathological findings share features similar to those observed in human
      patients and other animal models of filovirus infection. Reverse-transcription
      polymerase chain reaction analysis of host transcripts shows a dysregulation of
      the innate immune response. Our results demonstrate that the STAT2 knockout
      hamster represents a novel small animal model of severe MARV infection and
      disease without the requirement for virus adaptation.

PMID- 30192977
TI  - Bronchial hyper-responsiveness: a technical update.
AB  - Background: Bronchial hyper-responsiveness (BHR) is often regarded as a
      'hallmark' of asthma, and bronchoprovocation testing is frequently performed to
      support a diagnosis of asthma. The European Respiratory Society (ERS) and
      American Thoracic Society (ATS) have recently updated their technical standards
      and guidelines for performing methacholine challenge testing (MCT), the most
      commonly performed clinical test of BHR. Aims: To review the updated guidelines
      and discuss the various changes and their potential impact on clinicians.
      Methods: We performed a systematic review of references identified using Medline
      and hand searches of identified articles. Results: The new ERS and ATS guidelines
      recommend that MCT be performed using tidal breathing, not deep inspirations with
      breath holding, that results be reported as the PD20 (cumulative dose causing a
      20% fall in forced expiratory volume in 1 s [FEV1]), rather than PC20
      (concentration causing a 20% fall in FEV1), and that manufacturers of nebulizers
      and other delivery systems provide performance characteristics to allow
      calculation of PD20 values. Our preliminary survey found that the new guidelines
      are only slowly being adopted. Conclusions: Clinicians should be aware that
      recommended BHR testing methods, particularly for MCT, have changed. As a result,
      they should anticipate that test outcomes will increasingly be reported in terms
      of PD20, which will facilitate longitudinal assessment of their patients.
      Compliance with the new guidelines will increase the sensitivity of MCT in mild
      and asymptomatic asthmatics.

PMID- 30192978
TI  - Excessive daytime sleepiness and napping in cognitively normal adults:
      associations with subsequent amyloid deposition measured by PiB PET.
AB  - Study Objectives: To determine the association of excessive daytime sleepiness
      (EDS) and napping with subsequent brain beta-amyloid (Abeta) deposition in
      cognitively normal persons. Methods: We studied 124 community-dwelling
      participants in the Baltimore Longitudinal Study of Aging Neuroimaging Substudy
      who completed self-report measures of EDS and napping at our study baseline and
      underwent [11C] Pittsburgh compound B positron emission tomography (PiB PET)
      scans of the brain, an average +/-standard deviation of 15.7 +/- 3.4 years later
      (range 6.9 to 24.6). Scans with a cortical distribution volume ratio of >1.06
      were considered Abeta-positive. Results: Participants were aged 60.1 +/- 9.8
      years (range 36.2 to 82.7) at study baseline; 24.4% had EDS and 28.5% napped. In
      unadjusted analyses, compared with participants without EDS, those with EDS had
      more than 3 times the odds of being Abeta+ at follow-up (odds ratio [OR] = 3.37,
      95% confidence interval [CI]: 1.44, 7.90, p = 0.005), and 2.75 times the odds
      after adjustment for age, age2, sex, education, and body mass index (OR = 2.75,
      95% CI: 1.09, 6.95, p = 0.033). There was a trend-level unadjusted association
      between napping and Abeta status (OR = 2.01, 95% CI: 0.90, 4.50, p = 0.091) that
      became nonsignificant after adjustment (OR = 1.86, 95% CI: 0.73, 4.75, p =
      0.194). Conclusions: EDS is associated with more than 2.5 times the odds of Abeta
      deposition an average of 15.7 years later. If common EDS causes (e.g., sleep
      disordered breathing, insufficient sleep) are associated with temporally distal
      AD biomarkers, this could have important implications for AD prevention.

PMID- 30192979
TI  - Fast automated reconstruction of genome-scale metabolic models for microbial
      species and communities.
AB  - Genome-scale metabolic models are instrumental in uncovering operating principles
      of cellular metabolism, for model-guided re-engineering, and unraveling cross
      feeding in microbial communities. Yet, the application of genome-scale models,
      especially to microbial communities, is lagging behind the availability of
      sequenced genomes. This is largely due to the time-consuming steps of manual
      curation required to obtain good quality models. Here, we present an automated
      tool, CarveMe, for reconstruction of species and community level metabolic
      models. We introduce the concept of a universal model, which is manually curated
      and simulation ready. Starting with this universal model and annotated genome
      sequences, CarveMe uses a top-down approach to build single-species and community
      models in a fast and scalable manner. We show that CarveMe models perform closely
      to manually curated models in reproducing experimental phenotypes (substrate
      utilization and gene essentiality). Additionally, we build a collection of 74
      models for human gut bacteria and test their ability to reproduce growth on a set
      of experimentally defined media. Finally, we create a database of 5587 bacterial
      models and demonstrate its potential for fast generation of microbial community
      models. Overall, CarveMe provides an open-source and user-friendly tool towards
      broadening the use of metabolic modeling in studying microbial species and
      communities.

PMID- 30192982
TI  - Perinatal outcome in births after a previous cesarean section at high trial of
      labor rates.
AB  - INTRODUCTION: Trial of labor (TOLAC) is an option in most preganancies after a
      cesarean section The objective of the study was to compare perinatal outcome in
      TOLAC and non-TOLAC deliveries in a population with high TOLAC rates. MATERIAL
      AND METHODS: This was a cohort study based on population data from the Medical
      Birth Registry of Norway. We included term, cephalic, single, second deliveries,
      1989-2009, after a first cesarean section (n = 43 422). TOLAC, TOLAC failure, non
      TOLAC deliveries, and after high-risk and low-risk pregnancies (no risk/any
      risk), were compared with respect to offspring mortality, 5-minute Apgar score
      Apgar < 7 and < 4, transfer to a neonatal intensive care unit, and neonatal
      respiratory distress syndrome. RESULTS: Statistically significant differences
      were observed (P <0.05). In the low-risk group the offspring mortality was
      2.3/1000 in TOLAC compared with 0.9/1000 in non-TOLAC. In the high-risk group,
      the offspring mortality was 3.7/1000 in TOLAC compared with 0.9/1000 in non
      TOLAC, and the 5-minute Apgar score < 4 was 3.1/1000 in TOLAC compared with
      0.9/1000 in non-TOLAC. In both risk groups, TOLAC delivery had a higher rate of 5
      minute Apgar score < 7. In the low-risk group, non-TOLAC deliveries had a higher
      rate of neonatal respiratory distress syndrome than TOLAC deliveries.
      CONCLUSIONS: We observed higher risk of offspring mortality and lower 5-minute
      Apgar score in TOLAC than in non-TOLAC. Possible causes and preventive measures
      should be explored.

PMID- 30192981
TI  - Single molecule tracking reveals that the bacterial SMC complex moves slowly
      relative to the diffusion of the chromosome.
AB  - Structural Maintenance of Chromosomes (SMC) proteins and their complex partners
      (ScpA and ScpB in many bacteria) are involved in chromosome compaction and
      segregation in all kinds of organisms. We employed single molecule tracking
      (SMT), tracking of chromosomal loci, and single molecule counting in Bacillus
      subtilis to show that in slow growing cells, ~30 Smc dimers move throughout the
      chromosome in a constrained mode, while ~60 ScpA and ScpB molecules travel
      together in a complex, but independently of the nucleoid. Even an Smc truncation
      that lacks the ATP binding head domains still scans the chromosome, highlighting
      the importance of coiled coil arm domains. When forming a complex, 10-15
      Smc/ScpAB complexes become essentially immobile, moving slower than chromosomal
      loci. Contrarily, SMC-like protein RecN, which forms assemblies at DNA double
      strand breaks, moves faster than chromosome sites. In the absence of Smc,
      chromosome sites investigated were less mobile than in wild type cells,
      indicating that Smc contributes to chromosome dynamics. Thus, our data show that
      Smc/ScpAB clusters occur at several sites on the chromosome and contribute to
      chromosome movement.

PMID- 30192980
TI  - The methyltransferase domain of the Sudan ebolavirus L protein specifically
      targets internal adenosines of RNA substrates, in addition to the cap structure.
AB  - Mononegaviruses, such as Ebola virus, encode an L (large) protein that bears all
      the catalytic activities for replication/transcription and RNA capping. The C
      terminal conserved region VI (CRVI) of L protein contains a K-D-K-E catalytic
      tetrad typical for 2'O methyltransferases (MTase). In mononegaviruses, cap-MTase
      activities have been involved in the 2'O methylation and N7 methylation of the
      RNA cap structure. These activities play a critical role in the viral life cycle
      as N7 methylation ensures efficient viral mRNA translation and 2'O methylation
      hampers the detection of viral RNA by the host innate immunity. The functional
      characterization of the MTase+CTD domain of Sudan ebolavirus (SUDV) revealed cap
      independent methyltransferase activities targeting internal adenosine residues.
      Besides this, the MTase+CTD also methylates, the N7 position of the cap guanosine
      and the 2'O position of the n1 guanosine provided that the RNA is sufficiently
      long. Altogether, these results suggest that the filovirus MTases evolved towards
      a dual activity with distinct substrate specificities. Whereas it has been well
      established that cap-dependent methylations promote protein translation and help
      to mimic host RNA, the characterization of an original cap-independent
      methylation opens new research opportunities to elucidate the role of RNA
      internal methylations in the viral replication.

PMID- 30192984
TI  - Interaction network of the mitochondrial outer membrane protein Mcp3.
AB  - Mitochondria are organelles containing two membranes that are distinct in
      composition and function. A role of the mitochondrial outer membrane (MOM) is to
      mediate contact of the organelle with the rest of the cell. In yeast, the MOM
      contains about 40 different integral proteins. Recently, we described the MOM
      protein Mcp3, which can serve as a multicopy suppressor of loss of ERMES complex
      that mediates mitochondria-endoplasmic reticulum contacts. To shed further light
      on the role of Mcp3 in the MOM, we analyzed its physical interaction with other
      proteins. We show that Mcp3 interacts with the MOM protein Om45 and the inner
      membrane protein Aim19. Our observations hint toward a potential involvement of
      Mcp3 in a structural and/or functional link between both mitochondrial membranes.

PMID- 30192983
TI  - Disproportionate feedback interactions govern cell-type specific proliferation in
      mammalian cells.
AB  - In mammalian cells, the decision to maintain quiescence over proliferation
      commitment during G1 -S transition depends on more than one intertwined feedback
      interaction and is highly cell-type dependent. However, the precise role played
      by these individual feedback regulations in organizing such diverse proliferation
      dynamics is still poorly understood. Herein, we propose a predictive mathematical
      model of G1 -S transition in mammalian cells that reconciles distinct single-cell
      experimental observations in a cell-type specific manner. The model analysis
      reveals that the feedback motifs responsible for the G1 -S transition act in a
      disparate fashion to organize the cell-type specific proliferation response.
      Importantly, the proposed model can be effectively tuned to gain insights into
      the proliferation commitment of diverse mammalian cell types and can find wide
      applicability.

PMID- 30192985
TI  - Short-term tamoxifen treatment has long-term effects on metabolism in high-fat
      diet-fed mice with involvement of Nmnat2 in POMC neurons.
AB  - Short-term tamoxifen treatment has effects on lipid and glucose metabolism in
      mice fed chow. However, its effects on metabolism in mice fed high-fat diet (HFD)
      and the underlying mechanisms are unclear. Here, we show that tamoxifen treatment
      for 5 days decreases fat mass for as long as 18 weeks in mice fed HFD. Tamoxifen
      alters mRNA levels of some genes involved in lipid metabolism in white adipose
      tissue and improves glucose and insulin tolerance as well as hepatic insulin
      signaling for 12-20 weeks. Proopiomelanocortin (POMC) neuron-specific deletion of
      nicotinamide mononucleotide adenylyltransferase 2 (Nmnat2) attenuates the effects
      of tamoxifen on glucose and insulin tolerance. These data demonstrate that short
      term injection of tamoxifen has long-term effects on lipid and glucose metabolism
      in HFD mice with involvement of Nmnat2 in POMC neurons.

PMID- 30192986
TI  - Ameliorative effect of hesperidin on ligation-induced periodontitis in rats.
AB  - BACKGROUND: This study evaluated the ameliorative effect of hesperidin (HES), an
      anti-inflammatory flavanone, in rats with ligation (Lig)-induced periodontitis.
      METHODS: A total of 48 rats were randomly divided into non-ligation group (NL),
      Lig group, and two ligation-plus-HES groups (L+H). HES was administered
      immediately after ligature placement at a dose of 75 or 150 mg/kg by intragastric
      feeding. Destruction of the ligated maxillary second and mandibular first molars
      were evaluated by dental radiography, microcomputed tomography (micro-CT), and
      histometry performed after sacrificing the rats on the seventh day. The
      expression levels of interleukin (IL)-1beta, IL-6, and inducible nitric oxide
      synthase (iNOS) messenger (m)RNAs in the gingiva were determined by reverse
      transcription polymerase chain reaction. The expression of iNOS was examined by
      immunohistochemistry. RESULTS: The dental radiography and micro-CT findings
      revealed significantly increased alveolar bone loss in the Lig group, which was
      significantly prevented by HES. The histometry results revealed less gingival
      inflammation and connective tissue loss in the L+H groups compared with that in
      the Lig group. The mRNA expression levels of IL-6, IL-1 beta, and iNOS were
      significantly increased in the Lig group but were reduced in the L+H groups. The
      immunostaining results showed that the ligation-induced iNOS expression was also
      decreased by HES. CONCLUSIONS: Oral administration of HES promotes an
      ameliorative effect against the ligation-induced alveolar bone loss and
      effectively inhibits the production of proinflammatory mediators in rats with
      experimentally induced periodontitis. Therefore, HES may be a good candidate for
      modulating oral inflammatory diseases.

PMID- 30192987
TI  - Irrational fear of whole-brain radiotherapy: Are we doing our patients a
      disservice?

PMID- 30192988
TI  - Clinical, radiographic, and genetic characteristics of hypohidrotic ectodermal
      dysplasia: A cross-sectional study.

PMID- 30192989
TI  - Exposure to non-ionizing electromagnetic radiation of public risk prevention
      instruments threatens the quality of spermatozoids.
AB  - The use of artificial insemination in cattle breeding has evolved to global
      extent, and insemination doses are often shipped via air transport which requires
      strict radiation-based examinations. For the determination of effect of non
      ionizing radiation (NIR), to which are beings frequently exposed due to
      protection of airport or cultural event security, freshly ejaculated and
      cryopreserved bovine spermatozoa were used as experimental model. Following
      radiation with hand-held metal detector in various exposition times (0, 10 s, 15,
      30 and 60 min-groups FR, FR10, FR15, FR30 and FR60) the spermatozoa underwent
      motility and DNA fragmentation analyses. Study on cryoconserved semen treated
      with NIR was performed in time intervals 0, 10 s, 1 and 5 min (insemination doses
      radiated before cryoconservation-CB, CB10, CB1, CB5; samples radiated after
      freezing-CA, CA10, CA1 and CA5). Fresh semen and insemination doses radiated
      after cryoconservation showed significantly lower total and progressive motility.
      No effect on motility parameters was detected in semen extended with
      cryopreservative medium and radiated prior to freezing. Surprisingly, NIR showed
      a potential to stimulate spermatozoa velocity; however, the effect was modulated
      throughout the post-thawing incubation. Based on the DNA fragmentation assay,
      sperm DNA stayed intact. Present study underlines the potential harm of NIR,
      which is frequently used in everyday life, with overall adverse impact on human
      and animal reproduction. Current study also points out on interesting short-term
      spermatozoa stimulation induced by NIR.

PMID- 30192990
TI  - All about CDR transporters: Past, present, and future.
AB  - Drug resistance mechanisms in human pathogenic Candida species are continually
      evolving. Over the time, Candida species have acquired diverse strategies to
      vanquish the effects of various classes of drugs thereby, emanating as a serious
      life threat. Apart from the repertoire of well-established strategies, which
      predominantly comprise alteration, overexpression of drug targets, and chromosome
      duplication, Candida species have evolved a number of permeability constraints
      for antifungal drugs, via compromised drug import or increased drug efflux. For
      the latter, genome of Candida species harbour battery of exporters designated as
      Candida drug resistance genes. These genes predominantly encode membrane efflux
      transporters, which expel the incoming drugs and thus prevent toxic intracellular
      accumulation of drugs to manifest multidrug resistance. Such a phenomenon is
      restricted not only to Candida species but has been observed among many other
      pathogenic fungal species as well. Notably, the existence of large number of drug
      exporters in genomes of Candida species posits other pivotal roles for these
      efflux transporter proteins. The brief review discusses as to how the whole gamut
      of antifungal research has since been changed to include these new observations
      wherein reduced permeability of azoles across cell membrane of Candida cells is
      being implicated as one of the major determinants of antifungal susceptibilities,
      which all began with the identification of the first multidrug resistance gene
      CDR1, in Andre Goffeau's laboratory back in 1995.

PMID- 30192991
TI  - A Photoenzymatic NADH Regeneration System.
AB  - A photoenzymatic NADH regeneration system was established. The combination of
      deazariboflavin as a photocatalyst with putidaredoxin reductase enabled the
      selective reduction of NAD+ into the enzyme-active 1,4-NADH to promote an alcohol
      dehydrogenase catalysed stereospecific reduction reaction. The catalytic turnover
      of all the reaction components was demonstrated. Factors influencing the
      efficiency of the overall system were identified.

PMID- 30192992
TI  - The evolutionary significance of hippocampal neurogenesis.
AB  - Hippocampal neurogenesis (HN) has been implicated in a variety of hippocampus
      dependent behaviors in the laboratory but its evolutionary significance is still
      debated. Some authors have argued that HN is an adaptation while others argued it
      is an atavism. However, recent analyses lead to the conclusion that HN likely
      evolved concurrently with the dentate gyrus itself, both being dependent on a
      migration of neural stem and progenitor cells out of the periventricular zone
      that occurs during development. This may render the previous debates obsolete, as
      selective pressure was likely acting upon the mammalian dentate gyrus itself,
      with neurogenesis being a mere spandrel in dentate gyrus' evolution.

PMID- 30192993
TI  - Functional anatomy of the male reproductive system of the American lobster
      (Homarus americanus).
AB  - Despite supporting a valuable fishery, the reproductive system of the male
      American lobster (Homarus americanus) is poorly understood. The elongated H
      shaped testis is responsible for spermatogenesis and is composed of follicles, a
      common collecting duct with interlaced scattered striated muscles, and a serosa
      as an external wall. Sertoli cells are associated with the spermatogenesis that
      produces spermatozoa, which are transferred to the collecting duct through a
      temporary passageway. Spermatogenesis is asynchronous between follicles and
      occurs on a continuous basis. The anterior and posterior lobes of the testes are
      independent and connect to the vasa deferentia through the Y-shaped collecting
      tubules that have a different cell anatomy and function than the two organs they
      connect. The vas deferens is divided into four regions. Spermatophores, produced
      in the proximal vas deferens, are packets of spermatozoa encapsulated in a single
      layer-the spermatophoric wall, which is composed of mucopolysaccharide acid.
      Large dense ovoid granules and the seminal fluid, composed of acidic sulfated
      mucosubstances, are secreted in the median vas deferens. Spermatophores within
      these secreted substances (i.e., semen) are stored in the distal vas deferens
      that, with the spermiduct (last region of the vas deferens), is responsible for
      the extrusion of the semen by striated muscle contractions. Smooth muscles
      suggest a peristaltic movement of the spermatophores within the vas deferens.
      Finally, the gonopores and the first pair of pleopods (i.e., gonopod) move the
      semen to the female seminal receptacle during copulation.

PMID- 30192994
TI  - A causality dilemma: ARFID, malnutrition, psychosis, and hypomagnesemia.
AB  - We present a novel case of a woman with coincident occurrence of auditory and
      visual hallucinations, electrolyte disturbances, chloride unresponsive alkalosis,
      and an eating disorder. The patient was ultimately diagnosed with Gitelman
      syndrome comorbid with schizophreniform disorder and avoidant restrictive food
      intake disorder. Eating disorders are often associated with electrolyte
      abnormalities which, in turn, can cause or contribute to other neuropsychiatric
      symptoms. At the same time, psychotic disorders can lead to food intake aversions
      or overconsumption of fluids with associated effects on electrolyte balance. In
      this case, a third factor, Gitelman syndrome, resulted in persistent
      hypomagnesemia with metabolic alkalosis and, while separate from her eating
      disorder, simultaneously reinforced the patient's strong food preferences,
      excessive fluid intake, and excessive movement related to her complaints of
      persistent joint pain.

PMID- 30192996
TI  - How Fast Can Thiols Bind to the Gold Nanoparticle Surface?
AB  - Kinetics of gold nanoparticle surface modification with thiols can take more than
      one hour for completion. 7-mercapto-4-methylcoumarin can be used to follow the
      process by fluorescence spectroscopy and serves as a convenient molecular probe
      to determine relative kinetics. SERS studies with aromatic thiols further support
      the slow surface modification kinetics observed by fluorescence spectroscopy. The
      formation of thiolate bonds is a relatively slow process; we recommend one to two
      hour wait for thiol binding to be essentially complete, while for disulfides,
      overnight incubation is suggested.

PMID- 30192995
TI  - Acute and chronic exercise in patients with heart failure with reduced ejection
      fraction: evidence of structural and functional plasticity and intact angiogenic
      signalling in skeletal muscle.
AB  - KEY POINTS: The vascular endothelial growth factor (VEGF) responses to acute
      submaximal exercise and training effects in patients with heart failure with
      reduced ejection fraction (HFrEF) were investigated. Six patients and six healthy
      matched controls performed knee-extensor exercise (KE) at 50% of maximum work
      rate before and after (only patients) KE training. Muscle biopsies were taken to
      assess skeletal muscle structure and the angiogenic response. Before training,
      during this submaximal KE exercise, patients with HFrEF exhibited higher leg
      vascular resistance and greater noradrenaline spillover. Skeletal muscle
      structure and VEGF response were generally not different between groups.
      Following training, resistance was no longer elevated and noradrenaline spillover
      was curtailed in the patients. Although, in the trained state, VEGF did not
      respond to acute exercise, capillarity was augmented. Muscle fibre cross
      sectional area and percentage area of type I fibres increased and mitochondrial
      volume density exceeded that of controls. Structural/functional plasticity and
      appropriate angiogenic signalling were observed in skeletal muscle of patients
      with HFrEF. ABSTRACT: This study examined the response to acute submaximal
      exercise and the effect of training in patients with heart failure with reduced
      ejection fraction (HFrEF). The acute angiogenic response to submaximal exercise
      in HFrEF after small muscle mass training is debated. The direct Fick method,
      with vascular pressures, was performed across the leg during knee-extensor
      exercise (KE) at 50% of maximum work rate (WRmax ) in patients (n = 6) and
      controls (n = 6) and then after KE training in patients. Muscle biopsies
      facilitated the assessment of skeletal muscle structure and vascular endothelial
      growth factor (VEGF) mRNA levels. Prior to training, HFrEF exhibited
      significantly higher leg vascular resistance (LVR) (~15%) and significantly
      greater noradrenaline spillover (~385%). Apart from mitochondrial volume density,
      which was significantly lower (~22%) in HFrEF, initial skeletal muscle structure,
      including capillarity, was not different between groups. Resting VEGF mRNA
      levels, and the increase with exercise, was not different between patients and
      controls. Following training, LVR was no longer elevated and noradrenaline
      spillover was curtailed. Skeletal muscle capillarity increased with training, as
      assessed by capillary-to-fibre ratio (~13%) and number of capillaries around a
      fibre (NCAF ) (~19%). VEGF mRNA was now not significantly increased by acute
      exercise. Muscle fibre cross-sectional area and percentage area of type I fibres
      both increased significantly with training (~18% and ~21%, respectively), while
      the percentage area of type II fibres fell significantly (~11%), and
      mitochondrial volume density now exceeded that of controls. These data reveal
      structural and functional plasticity and appropriate angiogenic signalling in
      skeletal muscle of HFrEF patients.

PMID- 30192997
TI  - Cobalt-Based Metal-Organic Framework Nanoarrays as Bifunctional Oxygen
      Electrocatalysts for Rechargeable Zn-Air Batteries.
AB  - Owing to their high theoretical energy density, environmental benign character,
      and low cost, rechargeable Zn-air batteries have emerged as an attractive energy
      technology. Unfortunately, their energy efficiency is seriously plagued by
      sluggish oxygen evolution reaction (OER) and oxygen reduction reaction (ORR) that
      alternately occurs on air electrodes. Herein, we demonstrate Co-based metal
      organic framework (Co(bpdc)(H2 O)4 (bpdc=biphenyl -4, 4'-dicarboxylic acid), Co
      MOF) arrays as novel bifunctional oxygen electrocatalysts. The Co-MOF is in situ
      constructed on a three-dimensional graphite foam (GF) through a hydrothermal
      reaction. In a 1 m KOH aqueous solution, the resultant Co-MOF/GF exhibits an OER
      overpotential of only ~220 mV at 10 mA cm-2 , which is much lower than those for
      Ir/C and previously reported noble metal-free electrocatalysts. In conjunction
      with its ORR half-wave potential of 0.7 V (vs. RHE), the Co-MOF/GF manifests a
      greatly decreased potential gap of ~0.75 V in comparison with Pt/C-Ir/C couple
      and previously reported bifunctional oxygen electrocatalysts. Furthermore, an
      assembled rechargeable zinc-air battery using Co-MOF electrocatalyst in an air
      electrode delivers a maximum power density of 86.2 mW cm-2 and superior charge
      discharge performance. Microscopic, spectroscopic and electrochemical analyses
      prove that the initial Co-MOF is transformed into Co-oxyhydroxides during the OER
      and ORR process, which essentially serve as bifunctional active centers.

PMID- 30192998
TI  - Genomic evidence for asymmetric introgression by sexual selection in the common
      wall lizard.
AB  - Strongly selected characters can be transferred from one lineage to another with
      limited genetic exchange, resulting in asymmetric introgression and a mosaic
      genome in the receiving population. However, systems are rarely sufficiently well
      studied to link the pattern of introgression to its underlying process. Male
      common wall lizards in western Italy exhibit exaggeration of a suite of sexually
      selected characters that make them outcompete males from a distantly related
      lineage that lack these characters. This results in asymmetric hybridization and
      adaptive introgression of the suite of characters following secondary contact. We
      developed genomewide markers to infer the demographic history of gene flow
      between different genetic lineages, identify the spread of the sexually selected
      syndrome, and test the prediction that introgression should be asymmetric and
      heterogeneous across the genome. Our results show that secondary contact was
      accompanied by gene flow in both directions across most of the genome, but with
      approximately 3% of the genome showing highly asymmetric introgression in the
      predicted direction. Demographic simulations reveal that this asymmetric gene
      flow is more recent than the initial secondary contact, and the data suggest that
      the exaggerated male sexual characters originated within the Italian lineage and
      subsequently spread throughout this lineage before eventually reaching the
      contact zone. These results demonstrate that sexual selection can cause a suite
      of characters to spread throughout both closely and distantly related lineages
      with limited gene flow across the genome at large.

PMID- 30192999
TI  - Deep cervical lymph node ligation aggravates AD-like pathology of APP/PS1 mice.
AB  - The imbalance between production and clearance of amyloid-beta (Abeta) is a key
      step in the onset and development of Alzheimer's disease (AD). Therefore,
      reducing Abeta accumulation in the brain is a promising therapeutic strategy for
      AD. The recently discovered glymphatic system and meningeal lymphatic vasculature
      have been shown to be critical for the elimination of interstitial waste
      products, especially Abeta, from the brain. In the present study, ligation of
      deep cervical lymph nodes was performed to block drainage of this system and
      explore the consequences on Abeta-related pathophysiology. Five-month-old APP/PS1
      mice and their wild-type littermates received deep cervical lymphatic node
      ligation. One month later, behavioral testing and pathological analysis were
      conducted. Results demonstrated that ligation of dcLNs exacerbated AD-like
      phenotypes of APP/PS1 mice, showing more severe brain Abeta accumulation,
      neuroinflammation, synaptic protein loss, impaired polarization of aquaporin-4
      and deficits in cognitive and exploratory behaviors. These results suggest that
      brain lymphatic clearance malfunction is one of the deteriorating factors in the
      progression of AD, and restoring its function is a potential therapeutic target
      against AD.

PMID- 30193000
TI  - Visualization of zinc pyrithione particles deposited on the scalp from a shampoo
      by tape-strip sampling and scanning electron microscopy/energy dispersive X-ray
      spectroscopy measurement.
AB  - OBJECTIVE: Zinc pyrithione (ZnPT) is widely used as an anti-fungal active in
      commercial anti-dandruff (AD) shampoos. The AD efficacy of ZnPT is highly
      dependent on the deposition of ZnPT particles onto the scalp during the process
      of shampoo application and rinse-off. Since ZnPT materials with different
      particle sizes and morphologies have different deposition behaviours, the
      measurement of the actual ZnPT deposition is critical to understand the AD
      performance delivered by different ZnPT shampoos. The aim of this study is to
      develop a robust and reliable method for visualizing the particle size and
      morphology of ZnPT deposited on the scalp from AD shampoos. METHODS: Hair was
      washed with a commercially available AD shampoo containing ZnPT and zinc
      carbonate (ZnCO3 ). Tape strips were applied to collect the deposited particles
      from the scalp after AD shampoo application and rinse-off. The scalp tape strip
      samples were subjected to scanning electron microscopy/energy dispersive X-ray
      spectroscopy (SEM/EDX) measurement. The morphology of the ZnPT particles was
      visualized by SEM imaging and identification of ZnPT particles was confirmed by
      EDX analysis. RESULTS: For the commercial shampoo studied it was observed that
      two zinc-containing particulates with different morphologies and composition
      remained on the scalp after shampoo application and rinse-off. As indicated by
      the EDX spectra, the ZnPT particles deposited onto the scalp surface had
      polygonal crystal structures. ZnCO3 was also deposited onto the scalp surface.
      This material was mainly present as aggregated particulates. CONCLUSION: An ex
      vivo method that combines tape strip sampling and SEM/EDX has been developed for
      measuring and visualizing the particle size, morphology and composition of ZnPT
      deposited on the scalp from AD shampoos. This ex vivo measurement method provides
      higher imaging resolution and more chemical specificity than reflectance confocal
      microscopy (RCM). To the best of our knowledge, this is the first time that ZnPT
      particles were distinguishable from other zinc particles on the scalp. Moreover,
      the new method allows the microstructures of both ZnPT and other zinc particles
      on the scalp to be imaged.

PMID- 30193001
TI  - Urinary excretion of homocysteine thiolactone and the risk of acute myocardial
      infarction in coronary artery disease patients: the WENBIT trial.
AB  - OBJECTIVES: No individual homocysteine (Hcy) metabolite has been studied as a
      risk marker for coronary artery disease (CAD). Our objective was to examine Hcy
      thiolactone, a chemically reactive metabolite generated by methionyl-tRNA
      synthetase and cleared by the kidney, as a risk predictor of incident acute
      myocardial infarction (AMI) in the Western Norway B-Vitamin Intervention Trial.
      DESIGN: Single centre, prospective double-blind clinical intervention study,
      randomized in a 2 * 2 factorial design. SUBJECTS AND METHODS: Patients with
      suspected CAD (n = 2049, 69.8% men; 61.2-year-old) were randomized to groups
      receiving daily (i) folic acid (0.8 mg)/vitamin B12 (0.4 mg)/vitamin B6 (40 mg);
      (ii) folic acid/vitamin B12 ; (iii) vitamin B6 or (iv) placebo. Urinary Hcy
      thiolactone was quantified at baseline, 12 and 38 months. RESULTS: Baseline
      urinary Hcy-thiolactone/creatinine was significantly associated with plasma tHcy,
      ApoA1, glomerular filtration rate, potassium and pyridoxal 5'-phosphate
      (positively) and with age, hypertension, smoking, urinary creatinine, plasma
      bilirubin and kynurenine (negatively). During median 4.7-years, 183 patients
      (8.9%) suffered an AMI. In Cox regression analysis, Hcy-thiolactone/creatinine
      was associated with AMI risk (hazard ratio = 1.58, 95% confidence interval = 1.10
      2.26, P = 0.012 for trend; adjusted for age, gender, tHcy). This association was
      confined to patients with pyridoxic acid below median (adjusted HR = 2.72, 95% CI
      = 1.47-5.03, P = 0.0001; Pinteraction = 0.020). B-vitamin/folate treatments did
      not affect Hcy-thiolactone/creatinine and its AMI risk association. CONCLUSIONS:
      Hcy-thiolactone/creatinine ratio is a novel AMI risk predictor in patients with
      suspected CAD, independent of traditional risk factors and tHcy, but modified by
      vitamin B6 catabolism. These findings lend a support to the hypothesis that Hcy
      thiolactone is mechanistically involved in cardiovascular disease.

PMID- 30193002
TI  - Effect of perforation size and furcal lesion on stress distribution in mandibular
      molars: a finite element analysis.
AB  - AIM: To compare the effect of furcal perforations of various sizes on the
      biomechanical response of mandibular first molars with or without periodontal
      bone loss at the furcal region via three-dimensional (3D) finite element analysis
      (FEA). METHODOLOGY: The 3D geometric basic model was reconstructed from the micro
      computed tomographic images of an extracted mandibular first molar. Five
      different models were constructed from this molar in group 1 as follows: intact
      molar model, root filled (RCF) model and three models with furcal perforations
      (1, 2 and 3 mm in diameter) repaired with a calcium silicate-based cement (CSC).
      In group 2, a lesion simulating bone resorption at the furcal region was modelled
      on the models in group 1. A force of 200 N was applied to simulate normal
      occlusal loads. Static linear FEA was performed using the Abaqus software (Abaqus
      6.14; ABAQUS Inc., Providence, RI, USA). The maximum principal stresses (Pmax )
      and maximum displacement magnitude were evaluated. RESULTS: The range of Pmax
      values of the models in group 1, from high to low, was as follows: RCF + 3 mm
      perforation > RCF + 2 mm perforation > RCF + 1 mm perforation > RCF > intact
      model, and the range of Pmax values of the models in group 2 was as follows: RCF
      + 3 mm perforation + furcal lesion > RCF + 2 mm perforation + furcal lesion > RCF
      + 1 mm perforation + furcal lesion > RCF + furcal lesion > intact model + furcal
      lesion. All of the models in group 2 exhibited lower Pmax values and higher
      maximum displacement magnitude than their counterparts without lesions in group
      1. CONCLUSIONS: The size of the furcal perforation affected the accumulation and
      distribution of stress within the models. Mandibular molar teeth with large
      furcal perforations treated with a calcium silicate-based cement may be
      associated with an increased risk of fracture whether or not accompanied by bone
      resorption.

PMID- 30193003
TI  - Genome Editing Reveals Novel Thiotemplated Assembly of Polythioamide Antibiotics
      in Anaerobic Bacteria.
AB  - Closthioamide (CTA) is a unique symmetric nonribosomal peptide with six thioamide
      moieties that is produced by the Gram-positive obligate anaerobe
      Ruminiclostridium cellulolyticum. CTA displays potent inhibitory activity against
      important clinical pathogens, making it a promising drug candidate. Yet, the
      biosynthesis of this DNA gyrase-targeting antibiotic has remained enigmatic.
      Using a combination of genome mining, genome editing (targeted group II intron,
      CRISPR/Cas9), and heterologous expression, we show that CTA biosynthesis involves
      specialized enzymes for starter unit biosynthesis, amide bond formation,
      thionation, and dimerization. Surprisingly, CTA biosynthesis involves a novel
      thiotemplated peptide assembly line that markedly differs from known nonribosomal
      peptide synthetases. These findings provide the first insights into the
      biosynthesis of thioamide-containing nonribosomal peptides and offer a starting
      point for the discovery of related natural products.

PMID- 30193004
TI  - Identification of tyrosine autophosphorylation sites of Arabidopsis MEKK1 and
      their involvement in the regulation of kinase activity.
AB  - The MEKK1 kinase is a key regulator of stress signaling in Arabidopsis; however,
      little is known about the regulation of its kinase activity. Here, we found that
      recombinant MEKK1, expressed in both mammalian HEK293 cells and Escherichia coli,
      shows a mobility shift in SDS-PAGE, and immunoblotting detected phosphorylation
      of serine, threonine, and tyrosine residues. N-terminal deletions, site-directed
      mutagenesis, and protein phosphatase treatment revealed that the mobility shift
      results from autophosphorylation of the kinase domain. We identified the tyrosine
      autophosphorylation sites in the N-terminal region of MEKK1. Tyrosine to
      phenylalanine mutations decrease phosphorylation of the substrate MKK1,
      suggesting the important role of this residue in the regulation of MEKK1 kinase
      activity. The present study is the first to show that plant MAPKKKs are regulated
      by tyrosine phosphorylation.

PMID- 30193005
TI  - Anion Exchange at the Liquid/Solid Interface of Ultrathin Ionic Liquid Films on
      Ag(111).
AB  - Thin ionic liquid (IL) films play an important role in many applications. To
      obtain a better understanding of the ion distribution within IL mixture films, we
      sequentially deposited ultrathin layers of two ILs with the same cation but
      different anions onto Ag(111), and monitored their dynamic behaviour by angle
      resolved X-ray photoelectron spectroscopy. Upon depositing [C8 C1 Im][PF6 ] on
      top of a wetting layer of [C8 C1 Im][Tf2 N] at room temperature (RT), we found a
      pronounced enrichment of the [Tf2 N]- anions at the IL/vacuum interface, due to a
      rapid anion exchange at the IL/solid interface. In contrast, at 90 K, the [Tf2 N]
      anions remain at the IL/solid interface. Upon heating, we observe a
      rearrangement of the cations between 140 and 160 K, such that the octyl chains
      preferentially point towards the vacuum. Above 170 K, the ions start to become
      mobile, and at 220 K, the anion exchange is completed, with the [Tf2 N]- anions
      enriched at the IL/vacuum interface in the same way as found for deposition at
      RT. The temperature range for the anion exchange corresponds well to glass
      transition temperatures reported in literature. We propose two driving forces to
      be cooperatively responsible for the replacement/exchange of [Tf2 N]- at the
      IL/solid interface and its enrichment at the IL/vacuum interface. First, the
      adsorption energy of [C8 C1 Im][PF6 ] is significantly larger than that of [C8 C1
      Im][Tf2 N], and second, the surface tension of [C8 C1 Im][Tf2 N] is lower than
      that of [C8 C1 Im][PF6 ].

PMID- 30193006
TI  - Monovalent cation transporters at the plasma membrane in yeasts.
AB  - Maintenance of proper intracellular concentrations of monovalent cations, mainly
      sodium and potassium, is a requirement for survival of any cell. In the budding
      yeast Saccharomyces cerevisiae, monovalent cation homeostasis is determined by
      the active extrusion of protons through the Pma1 H+ -ATPase (reviewed in another
      chapter of this issue), the influx and efflux of these cations through the plasma
      membrane transporters (reviewed in this chapter), and the sequestration of toxic
      cations into the vacuoles. Here, we will describe the structure, function, and
      regulation of the plasma membrane transporters Trk1, Trk2, Tok1, Nha1, and Ena1,
      which play a key role in maintaining physiological intracellular concentrations
      of Na+ , K+ , and H+ , both under normal growth conditions and in response to
      stress.

PMID- 30193007
TI  - Enantioselective Synthesis of Indolines, Benzodihydrothiophenes, and Indanes by C
      H Insertion of Donor/Donor Carbenes.
AB  - We employ a single catalyst/oxidant system to enable the asymmetric syntheses of
      indolines, benzodihydrothiophenes, and indanes by C-H insertion of donor/donor
      carbenes. This methodology enables the rapid construction of densely substituted
      five-membered rings that form the core of many drug targets and natural products.
      Furthermore, oxidation of hydrazones to the corresponding diazo compounds
      proceeds in situ, enabling a relatively facile one- or two-pot protocol in which
      isolation of potentially explosive diazo alkanes is avoided. Regioselectivity
      studies were performed to determine the impact of sterics and electronics in
      donor/donor metal carbene C-H insertions to form indolines. This methodology was
      applied to a variety of substrates in high yield, diastereomeric, and
      enantiomeric ratios and to the synthesis of a patented indane estrogen receptor
      agonist with anti-cancer activity.

PMID- 30193008
TI  - Gender differences in eating disorder psychopathology across DSM-5 severity
      categories of anorexia nervosa and bulimia nervosa.
AB  - OBJECTIVE: This study examined whether patterns of eating-disorder (ED)
      psychopathology differed by gender across DSM-5 severity specifiers in anorexia
      nervosa (AN) and bulimia nervosa (BN). METHOD: We tested whether ED
      psychopathology differed across DSM-5 severity specifiers among 532 adults (76%
      female) in a residential treatment center with AN or BN. We hypothesized that
      severity of ED psychopathology would increase in tandem with increasing severity
      classifications for both males and females with AN and BN. RESULTS: Among females
      with BN, DSM-5 severity categories were significantly associated with increasing
      ED psychopathology, including Eating Disorder Examination-Questionnaire dietary
      restraint, eating concern, shape concern, and weight concern; and Eating Disorder
      Inventory drive for thinness and bulimia. ED psychopathology did not differ
      across DSM-5 severity levels for males with BN. For both males and females with
      AN, there were no differences in ED psychopathology across severity levels.
      DISCUSSION: Results demonstrate that DSM-5 severity specifiers may function
      differently for males versus females with BN. Taken together, data suggest DSM-5
      severity specifiers may not adequately capture severity, as intended, for males
      with BN and all with AN. Future research should evaluate additional clinical
      validators of DSM-5 severity categories (e.g., chronicity, treatment non
      response), and consider alternate classification schemes.

PMID- 30193009
TI  - Evaluation of periodontal ligament cell viability in different storage media
      based on human PDL cell culture experiments-A systematic review.
AB  - BACKGROUND/AIMS: The best treatment for an avulsed tooth is immediate
      replantation. If this is not possible, a proper transport medium is required for
      the maintenance of viability of the periodontal ligament cells (PDL). The aim was
      to systematically review the efficacy of different storage media used for the
      survival of PDL cells of avulsed teeth in the in vitro setting. METHODS: The
      search strategy was based on the MeSH keywords in PubMed/MEDLINE: "Transport
      media for avulsed teeth," "Storage media for avulsed teeth," "Knocked out teeth,"
      "Tooth avulsion," "Biological transport of avulsed tooth," "Cell survival of
      avulsed tooth," "Cell viability of avulsed tooth," "Tooth replantation," and
      "Periodontal ligament in avulsed teeth." The "AND" and "OR" Boolean operators
      were applied to combine keywords. Each study was evaluated for eight criteria,
      including use of human PDL, in vitro cell culture models, the number of passages,
      types of storage media, percentages of surviving PDL cells, pH and osmolality of
      storage media, and the type of test used to asses PDL viability. RESULTS: In 15
      selected studies, nine storage media (HBSS, tap water, DMEM, milk, saliva, 10%
      and 20% propolis, Gatorade, and Viaspan) were analyzed at six time points. For
      storage up to 2 hours, HBSS, DMEM, milk, 10% propolis, 20% propolis, and Viaspan
      conserved more than 80% of PDL viability. For storage at 24 hours, Viaspan showed
      best cell survival at 88.4%, followed by DMEM (70.9%) and 10% propolis (68.3%).
      Milk and HBSS showed similar PDL survival at 24 hours (57.2% and 57.3%,
      respectively). CONCLUSIONS: Milk remains the most convenient, cheapest, and
      readily available solution in most situations while also being capable of keeping
      PDL cells alive. Further studies are required to evaluate the efficacy of more
      commonly found storage media besides milk.

PMID- 30193010
TI  - Inhibition of Pro-Inflammatory Functions of Human Neutrophils by Constituents of
      Melodorum fruticosum Leaves.
AB  - In an initial screening, the dichloromethane extract from the leaves of Melodorum
      fruticosum showed distinct inhibitory effects on the release of interleukin-8 (IL
      8) in human neutrophils. Therefore, the aim of the present study was the
      phytochemical and pharmacological investigation of this extract, to better
      understand which compounds might be responsible for the anti-inflammatory effect.
      Phytochemical analysis led to the isolation of 12 known compounds and two new
      natural products, 5-hydroxy-6-(2-hydroxybenzyl)-4',7-dimethoxyflavanone (13) and
      2',4'-dihydroxy-3'-(2-hydroxybenzyl)-4,6'-dimethoxychalcone (14). The influence
      of the isolated compounds on the production and release of the pro-inflammatory
      factors IL-8, tumor necrosis factor alpha (TNF-alpha), reactive oxygen species
      (ROS), and adhesion molecules (CD62L and CD11b) in human neutrophils was
      evaluated. Three constituents, melodamide A, 2',4'-dihydroxy-4,6'
      dimethoxychalcone, and 2',6'-dihydroxy-4'-methoxychalcone, showed significant
      inhibition of IL-8 release (IC50 =6.6, 8.6, and 11.6 MUm, respectively) and TNF
      alpha production (IC50 =4.5, 13.3, and 6.2 MUm, respectively).

PMID- 30193011
TI  - Evaluation of diagnostic accuracy and a practical algorithmic approach for the
      diagnosis of renal masses by FNA.
AB  - BACKGROUND: The classification of renal neoplasms is essential for oncologic risk
      stratification and clinical management, and an accurate pretreatment pathologic
      diagnosis can provide useful guidance for active surveillance, minimally invasive
      ablative therapy, or surgical resection and can reduce the incidence of
      overtreatment. Previous studies evaluating the diagnostic accuracy of fine-needle
      aspiration (FNA) and core-needle biopsy (CNB) for renal masses are limited and
      show variable results. METHODS: Two hundred forty-seven renal FNA cases with or
      without concurrent CNB performed and/or reviewed at the Stanford University
      School of Medicine over the course of 20 years were identified.
      Cytohistopathologic correlation was performed for 77 cases with subsequent
      resection specimens. All available case materials were reviewed, and select cases
      were worked up further and reclassified as necessary. RESULTS:
      Cytohistopathologic correlation showed 96% diagnostic specificity and 83%
      sensitivity for renal FNA with or without concurrent CNB. Discordant cases were
      mostly attributed to sampling errors or suboptimal specimens (79%) and also
      included 2 non-renal cell carcinoma entities (1 case of angiomyolipoma and 1 case
      of a benign peripheral nerve sheath tumor) and 1 case involving misclassification
      of the renal cell carcinoma subtype. CONCLUSIONS: There is considerable value in
      FNA/CNB for the initial diagnosis of renal masses because of the high diagnostic
      specificity and sensitivity. Sensitivity is predominantly dependent on sufficient
      sampling, and additional potential diagnostic pitfalls include nonepithelial and
      rare entities. Judicious use of ancillary techniques is encouraged, especially
      when one is presented with a limited specimen, and this article presents a
      practical algorithmic approach to the diagnosis of renal masses using salient
      morphologic features and results from ancillary studies. Fine-needle aspiration
      is an accurate method for the diagnosis of renal masses. A practical diagnostic
      algorithm, based on salient morphologic and ancillary findings, is presented.

PMID- 30193012
TI  - Cationic Branched Polyethylenimine (BPEI) Disables Antibiotic Resistance in
      Methicillin-Resistant Staphylococcus epidermidis (MRSE).
AB  - Staphylococcus epidermidis is one of the most prevalent prokaryotic species on
      human skin and mucosal membranes that constitute the commensal flora. S.
      epidermidis has become one of the most common causes of primary bacteremia.
      Infections are difficult to diagnose because the pathogen has natural niches on
      human skin and the ability to adhere to inanimate surfaces via biofilms.
      Alarmingly, S. epidermidis has acquired resistance to many antibiotics, which
      presents a danger to human health. Known as methicillin-resistant S. epidermidis
      (MRSE), most clinical isolates of MRSE in North America exhibit beta-lactam
      resistance primarily due to the presence of mecA, a gene that bestows beta-lactam
      antibiotic resistance in a manner similar to methicillin-resistant Staphylococcus
      aureus (MRSA). MecA encodes for expression of penicillin-binding protein 2a
      (PBP2a), which is absent in beta-lactam susceptible strains of S. epidermidis. We
      can disable this resistance factor in MRSE with 600-Da branched polyethylenimine
      (BPEI). Cationic BPEI targets anionic wall teichoic acid (WTA), an essential
      cofactor for proper functioning of PBP2a. We found that BPEI synergizes the
      activity of beta-lactam antibiotics against MRSE. Growth curves suggest that the
      combination of BPEI and oxacillin is bactericidal. Electron micrographs indicate
      abnormalities in the cellular septa and cell walls of treated samples. Therefore,
      first-line clinical treatments can be effective against MRSE when used in
      combination with BPEI.

PMID- 30193013
TI  - Interface-Engineered Li7 La3 Zr2 O12 -Based Garnet Solid Electrolytes with
      Suppressed Li-Dendrite Formation and Enhanced Electrochemical Performance.
AB  - High grain-boundary resistance, Li-dendrite formation, and electrode/Li
      interfacial resistance are three major issues facing garnet-based solid
      electrolytes. Herein, interfacial architecture engineering by incorporating 1
      butyl-1-methylpyrrolidinium bis(trifluoromethylsulfonyl) imide (BMP-TFSI) ionic
      liquid into a garnet oxide is proposed. The "soft" continuous BMP-TFSI coating
      with no added Li salt generates a conducting network facilitating Li+ transport
      and thus changes the ion conduction mode from point contacts to face contacts.
      The compacted microstructure suppresses Li-dendrite growth and shows good
      interfacial compatibility and interfacial wettability toward Li metal. Along with
      a broad electrochemical window larger than 5.5 V and an Li+ transference number
      that practically reaches unity, LiNi0.8 Co0.1 Mn0.1 O2 /Li and LiFePO4 /Li solid
      state batteries with the hybrid solid electrolyte exhibit superior cycling
      stability and low polarization, comparable to those with commercial liquid
      electrolytes, and excellent rate capability that is better than those of Li-salt
      based ionic-liquid electrolytes.

PMID- 30193014
TI  - Graphical Cytometry.

PMID- 30193016
TI  - Small Is Beautiful* - or Is It?

PMID- 30193015
TI  - The Loneliness of Mental Illness at the End of Life.

PMID- 30193017
TI  - METRICS for Metrics.

PMID- 30193018
TI  - Defining the Place of Direct Primary Care in a Value-Based Care System.
AB  - INTRODUCTION: Direct primary care, one of several retainer-based practice models,
      is a niche practice type that offers an alternative to the traditional fee-for
      service and insurance-based practices most prevalent in US health care. In
      Wisconsin, the prevalence of direct primary care practices is higher than in most
      other states. The market for direct primary care practice may be growing along
      with the industry shift to value-based care and an increase in physicians' desire
      to reduce the increasing administrative work and regulations that detract from
      patient care and increase burnout. Many physicians are seeking ways to reduce
      these burdens so they have more time with patients. Some are transitioning their
      practice to a retainer-based model, such as direct primary care, in which they
      collect a retainer from patients in exchange for more time, freer communication,
      and less paperwork. OBJECTIVE: The objective of this review is to provide
      information about the direct primary care practice model, possible drivers to
      this model of care, and its advantages and drawbacks for physicians and patients.
      This discussion also aims to evaluate the care model's place in the shift to
      value-based care, and key positions and policy from leading organizations.
      METHODS: A literature review was conducted to collect and analyze current
      evidence about the prevalence of retainer-based practices, the average fees
      associated with such models, the contributors to physician burnout that may lead
      to a transition to the direct primary care model, and the relevant ethical and
      policy considerations associated with direct primary care. DISCUSSION: Eighty-two
      percent of Wisconsin physicians report some level of burnout. Estimates
      demonstrate an increase in the number of direct primary care practices, and that
      Wisconsin is among the top 3 states with the highest number of direct primary
      care practices. The literature suggests that since the early stages of modern
      retainer-based models, patient fees have decreased and the patient base for these
      practices has expanded. The practice model is relatively rare, although there are
      indicators that its presence has increased in recent years. CONCLUSIONS:
      Physicians seeking strategies to reduce administrative burden, spend more time
      with patients, or simply streamline their practice may experience benefits in
      transitioning to a retainer practice such as direct primary care. There are
      foundational concepts about direct primary care, including advantages, drawbacks,
      and ethical considerations, to heed when transitioning to this model. There is a
      need for further research to quantify key data about direct primary care and its
      effects on patient outcomes and physician burnout and satisfaction.

PMID- 30193020
TI  - Surveillance of Wisconsin Organisms for Trends in Antimicrobial Resistance and
      Epidemiology: Introduction to the Program and Summary of 2016 Geographic
      Variation.
AB  - BACKGROUND: Antimicrobial resistance merits surveillance because of its impact on
      quality health care. Past surveillance efforts in Wisconsin involved generation
      of a statewide antibiogram on the basis of antibiogram compilation. However, this
      modality of surveillance possesses limitations. METHODS: To characterize
      Wisconsin antimicrobial susceptibility patterns and elucidate geographic
      variation in antimicrobial resistance, a statewide surveillance network was
      created. Clinical microbiology laboratories submitted clinically significant
      bacterial isolates to a centralized testing facility for performance of
      standardized broth microdilution testing. Analyzed data included organism
      specific susceptible, intermediate, and resistant percentages, along with median
      and 90th percentile minimum inhibitory concentration values. RESULTS: In
      comparison of 378 isolates of Escherichia coli (E coli) and 279 isolates of
      Proteus mirabilis (P mirabilis), susceptibility rates of E coli were generally
      lower than P mirabilis, particularly in areas of Wisconsin bordering Lake
      Winnebago. P mirabilis resistance rates were generally higher in northern
      Wisconsin. From a 211-isolate collection of Pseudomonas aeruginosa, it was
      determined that higher rates of antimicrobial resistance were found in Southeast
      Wisconsin. On a geographic basis, susceptibility rates within a 212-isolate
      collection of Streptococcus pneumoniae were fairly consistent. However,
      Southcentral Wisconsin experienced increased rates of erythromycin resistance
      with this organism, as well as increased aminoglycoside resistance trending with
      other organisms. Antimicrobial agents with generally lower susceptibility rates
      statewide included fluoroquinolones and trimethoprim-sulfamethoxazole.
      CONCLUSIONS: A surveillance program has been initiated in Wisconsin that not only
      summarizes susceptibility patterns but also has the capacity to indicate
      potential emerging resistance trends. Future annual studies can begin to
      characterize antimicrobial resistance in Wisconsin on a temporal basis.

PMID- 30193019
TI  - Identifying Differences in Rates of Invitation to Participate in Tobacco
      Treatment in Primary Care.
AB  - INTRODUCTION: The progress achieved in reducing tobacco use has not been
      consistent across groups of smokers, and health systems are inconsistently
      implementing best practice guidelines. Guideline implementation could be
      associated with improved treatment invitation rates. AIMS: To evaluate
      differences in tobacco treatment invitation rates based on patient
      characteristics in primary care clinics implementing best practice guidelines.
      METHODS: A secondary analysis of patients presenting to 11 primary care clinics
      from 2 Wisconsin health systems from June 2010 to February 2013. The main outcome
      was whether patients received an invitation to participate in tobacco treatment.
      Invitation rates were examined by sex, age group (<= 24 years, 25-44, 45-64, >=
      64), race (white, black, other), insurance status (private, Medicare, Medicaid,
      none), and visit diagnosis ("high-risk" [cardiovascular and pulmonary disease,
      malignancy, pregnancy] vs "low-risk" [all other ICD-9 categories]). Moderation
      effects of health systems also were examined. RESULTS: Of the 95,471 patients
      seen, 84,668 (89%) were screened for smoking. Among the 15,193 smokers, 10,242
      (67%) were invited to participate. Invited patients were older, white or black,
      and carried low-risk diagnoses. Invitation rates and patient-level differences
      varied between the health systems. CONCLUSIONS: Variable treatment invitation
      rates and health system differences remain evident in the primary care setting
      employing robust clinical practice guideline recommendations.

PMID- 30193021
TI  - Screening Pediatric Patients for Food Insecurity: A Retrospective Cross-Sectional
      Study of Comorbidities and Demographic Characteristics.
AB  - BACKGROUND: Food insecurity is a household-level economic and social condition of
      limited or uncertain access to adequate and nutritional food that is associated
      with diabetes, obesity, anxiety, depression, and behavioral disorders. The
      presence of these comorbidities motivated the UW Health Pediatrics Department to
      start screening for food insecurity. METHODS: Our study describes demographic
      characteristics of screened patients, comparing risk factors and health status
      between food insecure patients and food secure patients. We extracted variables
      on all screened patients: sex, age, race, ethnicity, insurance type, height,
      weight (to calculate body mass index [BMI] and BMI percentile), and any diagnosis
      of diabetes, hypertension, sleeping problems, restless leg syndrome, anemia,
      elevated blood lead levels, depression, anxiety, or attention deficit
      disorder/attention deficit hyperactivity disorder (ADD/ADHD). RESULTS: Over the 8
      month screening period, 1,330 patients were screened for food insecurity, and 30
      screened positive. Insurance type was a significant predictor for food
      insecurity; patients on public or with no insurance had 6.39 times greater odds
      of being food insecure than those on private insurance (CI 3.81, 13.29). Also,
      diagnoses of anemia and ADD/ADHD were both significantly higher in the food
      insecure group. The odds of having anemia was 8.47 times greater for food
      insecure patients (CI 3.03, 23.63), and the odds for having ADD/ADHD was 5.89
      times greater for food insecure patients than food secure patients (CI 1.48,
      23.55). DISCUSSION: These results provide useful information to clinicians as the
      screening process moves toward widespread adoption. These results also provide a
      baseline for expanded research once screening is implemented throughout all
      pediatric clinics within our health care organization.

PMID- 30193022
TI  - Ultrasound-Enabled Noninvasive Management of Inadvertent Carotid Cannulation.
AB  - INTRODUCTION: Despite ultrasound use, accidental carotid cannulation is possible
      during placement of a central venous catheter (CVC), requiring operative repair
      of the carotid artery and removal of the catheter. CASE PRESENTATION: We report 2
      cases-a 59-year-old Hispanic man and an 86-year-old white man-of inadvertent
      placement of a CVC into the left common carotid artery, removed via a pull-and
      pressure technique under real-time ultrasound guidance. No complications occurred
      and follow-up imaging was negative for fistula creation, hematoma, or cerebral
      infarcts. DISCUSSION: Prior cases have reported accidental carotid cannulations
      that required operative repair. Our discussion focuses on the complications of
      removal of CVCs from the common carotid, and the utility, feasibility, and safety
      of using real-time ultrasound guidance in the removal. CONCLUSION: While
      operative removal of CVCs accidentally placed in the carotid is recommended, an
      ultrasound-enabled pull-and-pressure technique may prevent complications and
      avoid need for surgical repair in critically ill patients.

PMID- 30193023
TI  - Rapid Therapeutic Response of Eosinophilic Meningoencephalitis in a Toddler With
      Baylisascaris procyonis Infection.
AB  - INTRODUCTION: Eosinophilic meningitis is an infrequently encountered condition.
      Baylisascaris procyonis (raccoon roundworm) infection, rarely diagnosed in North
      America, is a known cause of eosinophilic meningitis, often producing death or
      permanent neurologic damage. CASE REPORT: We recently encountered a toddler with
      geophagia and probable exposure to raccoon feces, who presented with eosinophilic
      meningitis and encephalitis, and was diagnosed with B procyonis infection and
      possible Toxocara co-infection. His marked peripheral eosinophilia and neurologic
      symptoms rapidly responded to corticosteroid and albendazole therapy. DISCUSSION:
      Since B procyonis infection is infrequently encountered, its diagnosis in the
      proper clinical and epidemiologic setting may not always be considered, resulting
      in a delay of appropriate therapy. Our patient, diagnosed and treated early in
      his course, demonstrated rapid clinical and laboratory improvement with anti
      inflammatory and antiparasitic therapy. CONCLUSION: In cases of eosinophilic
      meningitis, infection with B procyonis should be routinely considered to allow
      timely institution of effective therapy for this unusual but potentially fatal or
      debilitating infection.

PMID- 30193024
TI  - Expanding Our Work: A Multifaceted Approach to Improving Mental Health Access.

PMID- 30193025
TI  - Wisconsin Health Care Making Progress Toward CMS Quality Strategy Goals.

PMID- 30193027
TI  - [The Risk Zone As A Factor Of Professional Burn-Out Of Medical Workers].
AB  - The article presents the results of study of risk zones and factors of
      professional burn-out of medical workers. The theoretical foundation of syndrome
      of emotional burn-out, features of professional activity and individual
      characteristics of public health professionals are revealed. The original study
      used the Maslach-Jackson technique adapted by N.E. Vodopyanova to determine
      levels of burn-out depending on age and career pattern. The risk zones of
      everyday professional activity include such external factors as unregulated
      duration of working time and high load per single specialist due to deficiency of
      physicians, inadequate level of social support and legal safety, absence of
      market mechanisms of compensation of health damage, absence of national patient
      oriented system within the framework of health care modernization,
      unpredictability of behavior of patients. The given priorities and difficulties
      are studied on the example of the Republic of Mari-El. The Republic takes
      measures concerning training of physicians (a special faculty is organized)
      social support and stimulation of medical workers in rural area is developed.
      However, there is deficiency of physicians, load per single physician increases,
      level of salary did not fit requirements of the May decrees of the President of
      the Russian Federation. The reduction of risk zones of professional burn-out will
      favor development of national patient-oriented health care system, introduction
      of automated work places for physicians and increasing of their qualification,
      development of comfortable environment and atmosphere of friendliness in medical
      organizations.

PMID- 30193026
TI  - [The Problems of Analysis of Medical Statistics Data].
AB  - The article presents the results of usability of medical statistics in complex
      automated analysis. It is demonstrated that processing of data of large volume is
      necessary both for stage of analysis and procedures of its preliminary
      processing. The article summarizes and classifies problems limiting quality of
      complex analysis of data of medical statistics. The algorithm is proposed
      including sequentially applied procedures supporting correct preparation of
      indices for further analysis. The algorithm was applied to 1.5 million of records
      of medical statistics collected in the Medial Informational Analytical Center of
      the Health Care Department of the Primorskiy Krai in 2004-2014.

PMID- 30193028
TI  - [The Analysis of Morbidity of Tuberculosis of Respiratory Organs of Women of
      Reproductive Age on the Territory of the Nizhny Novgorod Oblast].
AB  - The article presents analysis of epidemiological situation with tuberculosis of
      respiratory organs among women of reproductive age on the territory of the Nizhny
      Novgorod oblast in 2009-2013. The average age of women with primarily diagnosed
      tuberculosis of respiratory organs was 38.8 years. In dynamics, a trend was
      established directed to decreasing of indicator of morbidity of tuberculosis of
      respiratory organs among women of fertile age that testifies a certain
      stabilization of situation. Among patients with primarily diagnosed tuberculosis
      of respiratory organs at the territory of the region women of reproductive age
      (18-44 years) are dominated (60%). The higher values of index of morbidity of
      bacillary forms of tuberculosis of respiratory organs are noted. The patients
      being the most dangerous in epidemiological respect, with bacterioexcretion
      established by microscopy prevail. In the women aged 25-34 years main
      epidemiological indices exceed the average oblast indices that testifies
      epidemiological troubles in the oblast. Because women are a main group of
      population being a labor and reproductive potential of state, the organizational
      methodological activities are to be targeted to timely diagnostic of disease and
      increasing of quality of phthisiology care.

PMID- 30193029
TI  - [The Opinions of Physicians Concerning Organization of Medical Rehabilitation of
      Children].
AB  - The making of healthy society requires to attend a special medical attention to
      children population. The ill children of the first year of life set up a danger
      of development of chronic diseases in the elder age and in subsequent adult
      population. In Russia, during last years, both unfavorable and positive trends in
      newborns' health are observed. This occurrence dictates a necessity of studying
      regional characteristics and analyzing of medical social factors determining
      health stte of newborns. The total morbidity of children of the first year of
      life during last decade manifest a particular trend to decreasing (up to 4.84%)
      though in certain classes of diseases an increasing from 2% to 32% was observed.
      The implemented study demonstrated availability of a number of characteristics of
      process of rehabilitation of under age population in conditions of the Omsk
      region. The involvement of large number of professionally experienced physicians
      substantiates its high reliability from the positions of medical science. From
      professional point of view, the courses of medical rehabilitation for patients
      are to be applied no less than three times per a year. It is especially
      significant for patients of the first year of life because a direct dependence is
      detected concerning early beginning of rehabilitation activities and subsequent
      higher efficiency of treatment. In the Omsk oblast, the medical rehabilitation
      service provides a highly qualitative care to children. Though at that a limited
      accessibility of services of the specialized Center of medical rehabilitation to
      residents of remote municipal okrugs and oblast districts is established. Also, a
      lower quality of services in other municipal medical institutions was established
      as compared with the specialized Center. The rectification of actual situation is
      seen on the way of organizing of rehabilitation centers of departments in other
      municipal okrugs and districts of the Omsk oblast and increasing of capacity of
      the existing rehabilitation center.

PMID- 30193030
TI  - [The Social Hygienic Aspects of Prevention of Abortions].
AB  - The article presents results of analysis of medical social aspects of artificial
      abortion. It is established that women with abortion in anamnesis suffer of
      unsatisfactory health condition in 35.5% of all cases. In the control group
      number of women with such a condition was 2.1 times less (p<0.05). The women with
      abortions are not aware about contraceptives and assume that abortions are safer
      in 2.1 times more often than women in control group. To prevent occurrence of
      undesired pregnancy it is necessary to enhance sanitary education concerning
      application of contraceptives and to provide possibility of free provision of
      articles.

PMID- 30193031
TI  - [About the Issue of Organization of Primary Specialized Opthalmologic Care in
      Megalopolis].
AB  - The restriction of accessibility of primary specialized ophthalmologic medical
      care in polyclinics remains to be a main problem of its organization for
      population of large megalopolises. At that, similar medical services are actively
      provided by commercial optician's rooms. The purpose of study is to analyze
      perspectives of organization of primary specialized ophthalmologic medical
      sanitary care of population in large megalopolis. The questionnaire survey was
      carried out. The sampling included 4,248 patients of municipal polyclinics and
      120 patients of ophthalmologic rooms of commercial opticians. The patients
      estimate higher accessibility of medical services in ophthalmologic rooms of
      commercial opticians as compared with municipal polyclinics (88.4% and 76%
      correspondingly). The most of patients (86%) argue in favor of receiving medical
      services in ophthalmologic rooms of commercial opticians at the expense of means
      of mandatory medical insurance. The sampling of 178 ophthalmologists of municipal
      polyclinics were included in survey concerning perspectives of involvement of
      ophthalmologic rooms of commercial opticians to provision of ophthalmologic
      services. This direction was supported by 28.4% of respondents. The article
      presents estimates of planning of volumes of medical care of patients being in
      need of optical correction of vision in case of its rendering by ophthalmologic
      rooms of commercial opticians in large megalopolis.

PMID- 30193032
TI  - [The New Approaches to Organization of Medical Supplies Support of Patients in
      Hospital in Modern Conditions].
AB  - The article considers the results of complex scientific analysis of issues
      concerning medications' support of patients in hospital in modern conditions. The
      economic and social efficiency of proposed organizational methodological
      approaches to development of management of medications' support is demonstrated.

PMID- 30193033
TI  - [The Organization of Rehabilitation of Patients after Mastectomy].
AB  - The article substantiates necessity of team approach to rehabilitation of women
      suffering of breast cancer. The content of rehabilitation activities are
      determined and their role in amelioration of quality of life of patients as well.

PMID- 30193034
TI  - [N.A. Semashko, the First People's Commissar of Health Care].
AB  - The article is devoted to 100th anniversary of organization of the Narkomzdrav of
      the Russian Soviet Federal Socialist Republic. The input of N.A. Semashko, the
      People's Commissar of Health Care, is presented concerning organization of the
      state central board of the national medical sanitary business, organization of
      the Soviet health care system and development of its major principles. The
      archive sources were involved to through light upon other aspects of activity of
      N.A. Semashko, including struggle with arrests of physicians during the Civil
      War, circumstances of his displacement from the position of People's Commissar of
      Health Care, work as a director of the Institute of health care organization and
      history of medicine.

PMID- 30193035
TI  - [The History of International Associations of Museums of Medicine].
AB  - The article considers history of activity of international associations of
      museums of Europe and North America from the moment of organization of the first
      International Association of Medical Museums existed from 1907 to 1955 and to the
      European association of Museums of History of Medical Sciences (since 1983) and
      the Association of Medical Museums (since 1985) both existing at the present
      time. The analysis is presented concerning their role in unification of
      scientific community, development of research methods, determination and
      reconsideration of professional concepts and also alterations of functions of
      medical collections and museums with the course of time and new trends in medical
      education, clinical and fundamental medicine and museum business. The existence
      and development of museum associations is compared with concept of three "museum
      revolutions": professionalization of museum sector (at the turn of XIX-XX
      centuries), orientation on education of broad masses of population (second half
      of XX century), establishment of principles of social inclusion and multi
      culturality (beginning of XXI century). The method of study is analysis of such
      sources untranslated to Russian previously as archives of "Vestnik" and reports
      and also scientific publications of members of associations involved into their
      activities. The results of study determined possible directions of work related
      to coordination of activities of medical museums, development of scientific
      research and scientific education methods and exposition work. The conclusions
      are made about an important role of international associations in systematization
      of knowledge, organization of scientific activities and medical community,
      development of guidelines for regional museums and also organization of unified
      information space for workers of medical museums.

PMID- 30193036
TI  - [On Scientific Public Activity of V.D. Shervinsky Related to Establishment of
      Societies of Physicians and Organization of Congresses (from Materials of
      Personal Archive of V.D. Shervinsky)].
AB  - The article is based on original documents of portion of archive of professor
      V.D. Shervinsky being kept in the Department of History of Medicine of The
      Federal State Budget Scientific Institution "N.A. Semashko National Research
      Institute of Public Health". The article analyzes a number of documents from the
      mentioned archive testifying scientific public activities of V.D. Shervinsky
      related to establishment of the societies of physicians and organization of
      congresses of physicians. The active scientific public activities of professor
      V.D. Shervinsky continued up to 1930s.

PMID- 30193037
TI  - [The Notions of Pupils and Students about Sexually Transmitted Infections and
      Ways of Their Development].
AB  - The sexually transmitted infections are an actual medical social problem of the
      youth that negatively impacts natality because of high proportion in the
      structure of causes of infertility and miscarriage. The questionnaire survey was
      carried out on the sampling of 938 pupils and students of natural science and
      humanitarian specialties. It is established that those of acquiring natural
      science education in the issues related to sexually transmitted diseases more
      often trust professional sources of information (physicians and scientific
      publications) while humanitarians prefer Internet and social advertising. The
      profile of education has no impact on self-evaluation of possible infection,
      readiness to screening examination and visiting the physician in case of
      corresponding problems occurrence.

PMID- 30193038
TI  - [The Modern Characteristics and Trends of Tuberculosis Epidemiology in Samara].
AB  - The article presents the results of investigation of features of dynamics of main
      demographic indices characterizing epidemic condition with tuberculosis in Samara
      during last decade. The gender age, social and clinical structures of patients
      spotted for the first time.

PMID- 30193039
TI  - [The Analysis of Medication Load as a Basis of Optimization of Pharmaceutical
      Therapy of Exacerbation of Bronchial Asthma in Children].
AB  - The article considers factors favoring increasing of prevalence and provoking
      exacerbations of bronchial asthma among children. The possibilities of methods of
      DDD ? DU90% are demonstrated as applied to analysis of medication therapy.

PMID- 30193040
TI  - [The Many-Sided Activity of Professor Aleksey Ivanovich Doynikov].
AB  - The professor A.I. Doynikov is the founder of the Chair of Propaedeutics of
      Orthopedic Stomatology of the Moscow Medical Stomatological Institute, a well
      known stomatologist, inventor, one of the prominent national organizers of
      stomatological care. The article for the first time various spheres of his
      professional activities are marked out and analyzed.

PMID- 30193041
TI  - [ROLE OF MITOCHONDRIAL REACTIVE OXYGEN SPECIES IN LIPOPOLYSACCHARIDE-PROMOTED
      ACCUMULATION OF INTRACELLULAR LIPID DROPLETS].
AB  - It is known that in various cell types bacterial lipopolysaccharide (LPS) causes
      mitochondrial disfunction and promotes accumulation of triglycerides in
      intracellular lipid droplets. The precise mechanisms which mediate LPS-induced
      neutral lipid deposition remain poorly understood. In the present work performed
      on primary cultured epithelial cells isolated from the frog urinary bladder we
      studied the possible role of mitochondrial reactive oxygen species (mROS) in LPS
      in-duced alteration of lipid metabolism. It was shown that LPS stimulated ROS
      production, decrea- 705 sed fatty acids oxidation, enhanced intracellular
      triglyceride deposition and promoted the formation of lipid droplets visualized
      by Nile red staining. Pretreatment of cells with mitochondrial-tar-geted
      antioxidant MitoQ at dose 25 nM for 2 h almost completely eliminated all the
      above effects of LPS. In contrast to MitoQ, a-tocopherol was ineffective. The
      data obtained indicate that increase of mROS level is a critical factor that
      mediates LPS-induced intracellular deposition of neutral lipids in epithelial
      cells.

PMID- 30193042
TI  - [THE EFFECT OF THE WORD FREQUENCY IN RUSSIAN LANGUAGE ON MISMATCH NEGATIVITY
      (MMN) IN THE EVENT RELATED POTENTIALS (ERP)].
AB  - The present study is designed to establish how lexical frequency of Russian words
      influences the acoustic mismatch negativity (MMN) latency and amplitude. The
      event related potentials (ERP) were recorded according to the multi-deviant
      passive odd-ball paradigm by using Russian words with different lexical
      frequencies and pseudowords. We found that the high-frequency words presentation
      led to a significantly more pronounced MMN response relative to the low-frequency
      one. The high-frequency words also evoked an earlier response, indicating more
      rapid access to a frequently used lexical entry. We suggest that a more
      pronounced amplitude and an earlier latency of acoustic MMN of high-frequency
      versus low-frequency items is a result of the word memory traces activation as
      more strongly connected assemblies of neurons. The MMN amplitude and latency for
      words were partly matched with the MMN for pseudowords (the analog of high
      frequency word evoked the most pronounced response and the analog of low
      frequency word evoked the weakest response), but the MMN amplitude and latency
      for pseudowords were significantly more pronounced and longer. We interpret this
      as evidence that processing of meaningless or unknown items is longer and their
      discrimination is more late and inaccurate than the discrimination of meaningful
      and frequently activated language elements.

PMID- 30193043
TI  - [RECOGNITION OF ADULTS EMOTIONAL STATE OF TYPICALLY DEVELOPING CHILDREN AND
      CHILDREN WITH AUTISM SPECTRUM DISORDERS].
AB  - The goal of the study was the definition of adult's possibilities of recognition
      the emotional state of typically developing (TD) and children with autism
      spectrum disorders (ASD), by facial expression, vocalizations and speech signals.
      Participants in the study were children with ASD (F 84.0 according to ICD-10),
      aged 5-16 years (n = 25) and typically developing (TD) children aged 4-7 years (n
      = 60). The analysis of child behavior, vocalizations and speech was performed for
      the purpose of stimulus selection. The peculiarities of emotion state recognition
      of TD children and ASD children by adults (n = 514) were revealed. It is shown
      that the emotional states of ASD children are better recognized by the features
      of vocalizations and speech than by facial expression. This finding is promising
      in terms of development of children with methods for assessing the
      characteristics of their voices, and to create an automatic speech recognition
      system for the purpose of teaching children with atypical development.

PMID- 30193044
TI  - [CHARACTERISTICS OF LIPID METABOLISM AND COMPLICATIONS OF ARTERIAL HYPERTENSION
      DEPENDING ON THE PSYCHOSOMATIC STATUS OF THE PATIENT AND TREATMENT OPTIONS].
AB  - It is established that on the investigated physiological (body mass index, body
      fat, the index "waist circumference/hip circumference") and biochemical (total
      cholesterol, lipoproteins of high, low and very low density, triglycerides)
      indicators of a condition of the lipid metabolism group of patients highanxiety
      the phlegmatic and melancholic are groups at higher risk of developing
      complications of hypertension. I highanxiety the phlegmatic and melancholic,
      unlike the choleric and sanguine, the high content of atherogenic lipid fractions
      and obesity is combined not only with the highest level of complications, but
      three times the prevalence of acute myocardial infarction on acute ischemic
      stroke (3:1). Effect of antihypertensive therapy aimed at relief features of the
      psychosomatic status of patients, manifested prior 6 months compared with
      "empiric" treatment option; in addition, after 12 months of therapy the values of
      the investigated parameters approached or were equal in the groups of healthy
      persons of corresponding temperament and anxiety. Also decreased the number of
      complications of arterial hypertension. Antihypertensive therapy based on the
      relief features of psychosomatic status in patients with arterial hypertension,
      has proven to be more effective in groups highanxiety and lowanxiety patients.

PMID- 30193045
TI  - [SIGNALING PATHWAYS INVOLVED IN THE REGULATION OF PROTEIN METABOLISM IN SKELETAL
      MUSCLE].
AB  - The ability of muscle cells to respond to certain signaling molecules depends on
      the presence of specific proteins-receptors, ion channels and transporters, which
      create a system of metabolic inputs. All cells in the human body have a
      transmembrane signaling system that allows to get information from extracellular
      stimuli such as hormones, neurotransmitters, proteins, peptides, derivatives of
      amino acids and fat acids, sensor molecules. The results of researches published
      in the last two years, which expand knowledge of action of various factors on
      protein metabolism in skeletal muscles are presented in the review. The main
      attention is turned to the discovery and expansion of signaling pathways involved
      in the regulation of protein metabolism in skeletal muscle in different
      functional states of the person.

PMID- 30193046
TI  - [THE ROLE OF AUTOANTIBODIES TO THE EXTRACELLULAR REGIONS OF IONOTROPIC RECEPTORS
      IN ETIOLOGY AND PATHOGENESIS OF AUTOIMMUNE DISEASES].
AB  - In the last years it was shown that autoantibodies to the extracellular regions
      of the ionotropic receptors, such as glutamate AMPA- and NMDA-receptors, GABAA
      receptors, glycine and nicotinic acetylcholine receptors, induce a wide spectrum
      of autoimmune diseases, including limbic encephalitis, Rasmussen's encephalitis,
      systemic lupus erythematosus, myasthenia gravis, encephalomyelitis, and stiff-man
      syndrome. In the review the literature data concerning the autoimmune processes
      provoking autoantibodies formation to the ionotropic receptors, the epitopes
      participating in the induction of pathogenic autoantibodies, and the effects of
      these antibodies on the functions of nervous cells and their role in the
      development of autoimmune diseases were analyzed and systematized. The possible
      role of oncology diseases in the generation of autoantibodies to the ionotropic
      receptors was discussed. Approaches that are currently being developed to inhibit
      the synthesis of pathogenic autoantibodies and to their neutralization were
      considered. These approaches may be subsequently used to treat the autoimmune
      diseases caused by the antibodies to ionotropic receptors.

PMID- 30193047
TI  - [INVOLVEMENT OF NITRIC OXIDE CYNTHASE IN THE EARLY PHASE OF THE HEART ISCHEMIC
      PRECONDITIONING].
AB  - Currently there is no single answer on the question of the participation of
      nitric oxide and NO-synthase (NOS) in the cardioprotection in the early phase of
      ischemic preconditioning (IP). In the present review the results of experimental
      studies indicate the involvement of NOS in the protective effect of IP and the
      literature data refuting this assumption. In addition, it was presented data on
      the increase of nitrates and nitrites (the stable metabolite of NO) in myocardial
      tissue after the IP, an increase in the expression of genes encoding NOS
      immediately after the IP, the data on the elimination of the protective effect of
      IP of NOS blockers and of imitation of IP affects IP by nitric oxide donors. It
      was exhibited a brief analysis of some of the studied mechanisms involving NO and
      NOS in cardioprotection at IP.

PMID- 30193048
TI  - [RATIO OF PREFRONTAL CORTEX NEURAL ACTIVITY BOTH HEMISPHERES DURING TASK OF
      CHOICE IN THE TWO-RING MAZE].
AB  - Neural activity in two symmetrical areas of the prefrontal cortex left and right
      hemispheres of the rat brain (55 and 47 neurons, respectively) were recorded
      during the execution of behavioral tasks in the two-ring maze. Experiments were
      carried out in two different conditions - task with the key, when only
      appropriate side to signal was reinforced, and without a key, when any choice was
      reinforced. Differential neural activity was estimated - the level of difference
      in firing on the right and left choice. When the animal did not guided by
      external keys (two behavioral situations: trails in a behavior block without any
      keys or error trails in behavior block with key presentation) there was observed
      prevalence of differential activity in the left hemisphere. The prevalence in the
      right hemisphere was observed in the correct trials in behavior block with key
      presentation. Apparently this is evidence of the dynamics in the hemispheric
      balance, depending on the external and internal conditions and the special role
      of the right hemisphere in the mechanisms of learning and inclusion of external
      determinants of the adaptive behavior response.

PMID- 30193049
TI  - [THE PULMONARY HEMODYNAMICS FOLLOWING EXPERIMENTAL PULMONARY THROMBOEMBOLISM AND
      AFTER BLOCKADE OF THE ALPHA-ADRENOCEPTORS].
AB  - In acute experiments on the anesthetized rabbits the pulmonary hemodynamics
      changes following pulmonary thromboembolism were studied in animals with intact
      circulation and isolated lungs perfusion in the control series and after the
      blockade of the alpha-adrenoceptors. Following pulmonary embolism in animals with
      intact circulation in the control group and after the blockade of alpha
      adrenoceptors the pulmonary artery pressure and pulmonary vascular resistance
      increased, but the pulmonary artery flow decreased to the same extent. However,
      in control animals, the cardiac output decreased more, than the pulmonary flow;
      the superior vena cava flow was decreased less, than inferior vena cava flow.
      After the blockade of the alpha-adrenoceptors there were no any imbalance between
      the decreasing of the cardiac output and pulmonary flow as well as between the
      decreasing of superior and inferior venae cavae flows. In animals with perfused
      lungs after the blockade of the alpha-adrenoceptors the pulmonary artery pressure
      following pulmonary embolism increased to the same level as in animals with
      intact circulation, however, in the first case the pulmonary vascular resistance
      increased four times less than in the last one. Thus, we concluded, that
      following pulmonary thromboembolism the activation of the alpha adrenergic
      mechanisms could not only promote to increase the resistance of the pulmonary
      vessels, but these mechanisms are also involved in the changes of the capacitive
      function of the pulmonary vessels.

PMID- 30193050
TI  - [EFFECT OF MAST CELL DEGRANULATION BLOCKADE ON THE INFLAMMATION OUTCOME IN THE
      MODEL OF OBSTRUCTIVE LUNG PATHOLOGY].
AB  - Effect of mast cell degranulation blockade on the inflammatory response and
      character of the lung tissue structure-functional changes were evaluated in the
      chronic obstructive pulmonary disease model produced in rats by 60-day
      intermittent exposure to nitrogen dioxide. The membrane stabilizer sodium
      cromoglicate was used to blockade of mast cell degranulation. Lung tissue
      sections were stained with toluidine blue to identify mast cells. Bronchoalveolar
      lavage fluid (BALF) cytogram was determined. The levels of mast cell tryptase and
      chymase, proinflammatory cytokine TNF-alpha, surfactant protein B were measured
      in BALF. Suppression of mast cell degranulation prevented the release of
      proteases in the bronchoalveolar space and reduced activity of the inflammatory
      process. The influx of inflammatory cells and TNF-alpha concentration decreased.
      There was no interstitial inflammatory infiltration. Bronchoalveolar epithelium
      structure was recovered that is the basis of its functional usefulness. The
      results confirm the active involvement of mast cells in the development of the
      inflammatory process in obstructive pulmonary diseases and allow us to consider
      them as a possible therapeutic target.

PMID- 30193051
TI  - [CHANGES OF THE OXIDATIVE STATUS, MITOCHONDRIAL FUNCTION, BLOOD PRESSURE AND
      INDICATORS OF HEMOSTASIS IN STRESSED ANIMALS AND IN THE CONDITIONS OF NO-SYNTHASE
      BLOCKADE].
AB  - Changes in the metabolism of female rats hanging by cervical dorsal skin fold
      within 24 hours were examined. It was found that stress exposure results in an
      increase of the concentration of the final nitric oxide metabolites in the blood
      serum and homogenates of the heart and brain of animals, intensification of
      processes peroxidation lipids and mitochondrial dysfunction in these organs. Thus
      increase of mean arterial blood pressure by 18.9 % from baseline and violation of
      platelet and plasma components of hemostasis. Inhibitor of neuronal NO-synthase 7
      nitroindazole in the dose of 50 mg/kg aggravates of the studied parameters
      changes. Administration of an animal selective inhibitor of inducible NOS
      aminoguanidine (50 mg / kg) contributes to limiting the damaging effects of
      stress reaction.

PMID- 30193053
TI  - [CHRONIC UNPREDICTABLE STRESS OF PREGNANT RATS AND HEALTH OUTCOMES OF THEIR
      OFFSPRING].
AB  - It was established that chronic unpredictable stress, which was reproduced by
      repeated exposure of adverse factors on the pregnant rats (food deprivations
      during one day, immobilization in the water of room temperature and contact with
      Felis excrements) results in the stable and sex-specific offspring's behavioural
      changes in the "open field" test, disorders of motor and coordinator functions
      and the increased sensitivity to pain at the age of both 1 and 3 months. Male and
      female rats, which were exposed to the prenatal stress, demonstrate elevated
      blood pressure. Enhanced lipoperoxidation in the blood serum of male rats after
      prenatal stress was indicated. Thus, prenatal stress leads to the stable
      alteration of the reactivity, which may favour persistent social maladjustment
      and the development of different pathologies.

PMID- 30193052
TI  - [STRESS-PROTECTIVE EFFECT OF HUMAN LACTOFERRIN].
AB  - Lactoferrin - multifunctional glycoprotein of the transferrin family with a
      molecular mass of about 80 kDa. We studied the effect of human lactoferrin on
      stress-induced changes in the level of corticosterone and adrenocorticotropic
      hormone (ACTH) and redistribution of leukocytes in the blood of rats. The used
      model of stress - swimming in cold water (1-4  degrees C) for 2 minutes.
      Corticosterone and ACTH levels in the plasma were determined by enzyme
      immunoassay. It has been established that preventive intraperitoneal
      administration of lactoferrin has reduced stress-induced increase in the
      concentration of corticosterone in 30 minutes after the stress and has normalized
      stress-inducing changes in the number of neutrophils in the blood after 30
      minutes and 3 hours after exposure of stress, but has not affected the level of
      ACTH. The results of this study suggest that lactoferrin can act as an adaptogen
      during experimental stress.

PMID- 30193054
TI  - [A MODULATORY INFLUENCE OF THE iNOS ON THE FUNCTIONAL ACTIVITY OF THE KATP
      CHANNELS IN CORONARY VESSELS OF RATS ADAPTED TO THE STRESS].
AB  - In the experiments carried out on the isolated by Langendorff's method hearts
      which were perfused at the constant coronary flow it was studied influence of
      iNOS-derived NO on the functional activity of the KATP-channels in the coronary
      vascular smooth muscle cells following formation of the adaptation to the stress.
      As an adaptation to the short stress as a 6-hours immobilization stress result in
      increase of NO production and rise of expression of gene iNOS; however,
      adaptation in contrast to the stress leads to moderate accumulation of iNOS
      against the background unchanged systemic activity of eNOS and in the absence of
      systemic low-grade inflammation. After an adaptation to the short stress or after
      6 hours of immobilization the functional glybenclamid-inhibiting activity of the
      KATP-channels was suppressed. Nevertheless, after prolonged immobilization
      suppressed activity of the channels was abolished after blockage of iNOS, whereas
      iNOS blockage in adapted animals leads not only to the recovery but even to the
      hyperactivation of the KATP-channels. Hence, increase in NO production which is
      typical for the adaptation, limits activation of the KATP-channels thus creating
      a strong link between these channels activity and NO produced by iNOS.

PMID- 30193055
TI  - [PARTICIPATION OF UROKINASE RECEPTOR AND ITS ENDOGENOUS LIGANDS IN BRAIN
      DEVELOPMENT AND FORMATION OF COGNITIVE FUNCTIONS].
AB  - Recently it has been found that the urokinase receptor (uPAR) and its ligands -
      urokinase (uPA) and SRPX2 protein play an important role in the development and
      functioning of the brain. There is a strong association between uPAR gene
      polymorphism and autism disorders in humans. Patients with autism, intractable
      lobe epilepsy, verbal dyspraxia and perisylvian polymicrogyria display
      significant changes in uPAR expression. Mice, lacking the uPAR gene develop
      epilepsy and demonstrate abnormal social behavior. uPA and SRPX2 protein, have
      been shown to be involved in pathological brain conditions such as autism,
      cognitive deficits and language disorders. Urokinase system that stimulates blood
      vessel growth as demonstrated before, also plays an important role in the
      regulation of the nerve growth via matrix remodeling and activation of
      neurotrophic and angiogenic factors. Moreover, the urokinase system also
      functions as a guidance system which determines the growth trajectory of the
      vessels' and nerves' in tissue regeneration. This review summarizes and
      integrates the results and recent progress in the field of uPAR and its
      endogenous ligands in brain development and cognitive functions.

PMID- 30193056
TI  - Ciliary Defects in a Mouse Model of Bardet-Biedl Syndrome are Selectively
      Pronounced in Brian Regions Involved in Cardiovascular Regulation.
AB  - Bardet-Biedl syndrome (BBS) is a human genetic disorder associated with several
      phenotypes including hypertension. Here we used the hypertensive Bbs4 knockout
      mouse model (Bbs4-/-) to test the hypothesis that areas of the brain involved in
      cardiovascular regulation (CVR) exhibit abnormalities in primary neuronal cilia
      (PNC) structure and density. We utilized immunocytochemical localization of
      adenylyl cyclase-III (ACIII), a specific marker for PNC, to identify the changes
      in PNC length and density in commissural nucleus of solitary tract (cNTS), area
      postrema (AP), rostroventrolateral medulla (RVLM) and subfornical organ (SFO). A
      quantitative analysis of the morphology and distribution of ACIII-immunoreactive
      PNC revealed dramatic alterations in the length and number of cilia in SFO of
      Bbs4-/- mice compared to wild type (WT) littermates. The significant reduction in
      the PNC length but not in the number was observed in cNTS and RVLM. Surprisingly,
      no significant changes in length and distribution of PNC were documented in the
      AP. We found that in all investigated areas of the brain the number of neurons
      did not display significant changes in Bbs4-/- when compared to the corresponding
      areas of WT mice. This data suggests that loss of the Bbs4 gene differentially
      affects the PNC in the brain areas involved in CVR; and the pathology of PNC in
      selected regions of CVR can cause a failure in signal transduction and may
      contribute to the hypertension associated with Bbs4-/- mouse model.

PMID- 30193057
TI  - Metal-Organic Framework Derived Spindle-like Carbon Incorporated alpha-Fe2O3
      Grown on Carbon Nanotube Fiber as Anodes for High-Performance Wearable Asymmetric
      Supercapacitors.
AB  - Iron oxide (Fe2O3) has drawn much attention because of its high theoretical
      capacitance, wide operating potential window, low cost, natural abundance, and
      environmental friendliness. However, the inferior conductivity and insufficient
      ionic diffusion rate of a simple Fe2O3 electrode leading to the low specific
      capacitance and poor rate performance of supercapacitors have impeded its
      applications. In this work, we report a facile and cost-effective method to
      directly grow MIL-88-Fe metal-organic framework (MOF) derived spindle-like alpha
      Fe2O3@C on oxidized carbon nanotube fiber (S-alpha-Fe2O3@C/OCNTF). The S-alpha
      Fe2O3@C/OCNTF electrode is demonstrated with a high areal capacitance of 1232.4
      mF/cm2 at a current density of 2 mA/cm2 and considerable rate capability with
      capacitance retention of 63% at a current density of 20 mA/cm2 and is well
      matched with the cathode of the Na-doped MnO2 nanosheets on CNTF (Na-MnO2
      NSs/CNTF). The electrochemical test results show that the S-alpha
      Fe2O3@C/OCNTF//Na-MnO2 NSs/CNTF asymmetric supercapacitors possess a high
      specific capacitance of 201.3 mF/cm2 and an exceptional energy density of 135.3
      MUWh/cm2. Thus, MIL-88-Fe MOF derived S-alpha-Fe2O3@C will be a promising anode
      for applications in next-generation wearable asymmetric supercapacitors.

PMID- 30193058
TI  - Rhodium Nanoparticles/F-Doped Graphene Composites as Multifunctional
      Electrocatalyst Superior to Pt/C for Hydrogen Evolution and Formic Acid Oxidation
      Reaction.
AB  - Highly efficient electrocatalysis for clean, efficient, and sustainable energy
      supply, such as hydrogen evolution reaction (HER) and formic acid oxidation
      reaction (FAOR), has drawn enthusiastic and worldwide attention. Universal and
      efficient electrocatalysts for these reactions are essential elements for the
      development of renewable and clean energy technologies. Herein, we show the
      design and fabrication of the rhodium nanoparticles modified fluorine-doped
      graphene (Rh/F-graphene) catalyst using silicon nanowires (SiNWs) as the
      sacrifice template. The optimized Rh/F-graphene catalyst (Rh/F-graphene-2) has a
      low Rh mass fraction of 9.4% and F doping of 4.0%. The mean diameter of Rh is
      9.39 nm. Rh/F-graphene-2 serves as a proton-adsorption-dominated multifunctional
      electrocatalyst for both HER and FAOR with performance superior to 20 wt % Pt/C
      in acidic solution. In addition, due to the doping of fluorine, the stability of
      Rh/F-graphene-2 catalyst greatly improves and is the best among all the compared
      electrocatalysts. This design for multifunctional catalysts could greatly
      increase the utilization ratio of Rh, which may provide a new avenue for the
      preparation of other noble metal-based catalysts.

PMID- 30193059
TI  - The Impact of Core/Shell Sizes on the Optical Gain Characteristics of CdSe/CdS
      Quantum Dots.
AB  - Colloidal quantum dots (QDs) are highly attractive as the active material for
      optical amplifiers and lasers. Here, we address the relation between the
      structure of CdSe/CdS core/shell QDs, the material gain they can deliver, and the
      threshold needed to attain net stimulated emission by optical pumping. On the
      basis of an initial gain model, we predict that reducing the thickness of the CdS
      shell grown around a given CdSe core will increase the maximal material gain,
      while increasing the shell thickness will lower the gain threshold. We assess
      this trade-off by means of transient absorption spectroscopy. Our results confirm
      that thin-shell QDs exhibit the highest material gain. In quantitative agreement
      with the model, core and shell sizes hugely impact on the material gain, which
      ranges from 2800 cm-1 for large core/thin shell QDs to less than 250 cm-1 for
      small core/thick shell QDs. On the other hand, the significant threshold
      reduction expected for thick-shell QDs is absent. We relate this discrepancy
      between model and experiment to a transition from attractive to repulsive exciton
      exciton interactions with increasing shell thickness. The spectral blue-shift
      that comes with exciton-exciton repulsion leads to competition between stimulated
      emission and higher energy absorbing transitions, which raises the gain
      threshold. As a result, small-core/thick-shell QDs need up to 3.7 excitations per
      QD to reach transparency, whereas large-core/thin shell QDs only need 1.0, a
      number often seen as a hard limit for biexciton-mediated optical gain. This makes
      large-core/thin-shell QDs that feature attractive exciton-exciton interactions
      the overall champion core/shell configuration in view of highest material gain,
      lowest threshold exciton occupation, and longest gain lifetime.

PMID- 30193060
TI  - Role of Filler Porosity and Filler/Polymer Interface Volume in Metal-Organic
      Framework/Polymer Mixed-Matrix Membranes for Gas Separation.
AB  - Metal-organic frameworks (MOFs) and inorganic fillers are frequently incorporated
      into mixed-matrix membranes (MMMs) to overcome the traditional trade-off in
      permeability ( P) and selectivity for pure organic polymer membranes. Therefore,
      it is of great interest to examine the influence of porous and nonporous fillers
      in MMMs with respect to the possible role of the polymer-filler interface, that
      is, the void volume. In this work, we compare the same MOF filler in a porous and
      nonporous state, so that artifacts from a different polymer-filler interface are
      excluded. MMMs with the porous MOF aluminum fumarate (Al-fum) and with a
      nonporous dimethyl sulfoxide solvent-filled aluminum fumarate (Al-fum(DMSO)),
      both with Matrimid as polymer, were prepared. Filler contents ranged from 4 to 24
      wt %. Gas separation performances of both MMMs were studied by mixed gas
      measurements using a binary mixture of CO2/CH4 with gas permeation following the
      theoretical prediction by the Maxwell model for both porous and nonporous
      dispersed phase (filler). MMMs with the porous Al-fum filler showed increased CO2
      and CH4 permeability with a moderate rise in selectivity upon increasing filler
      fraction. The MMMs with the nonporous Al-fum(DMSO) filler displayed a reduction
      in permeability while maintaining the selectivity of the neat polymer. A linear
      dependence of log P versus the reciprocal specific free fractional volume (sFFV)
      rules out a significant contribution from a void volume. The sFFV includes the
      free volume of the polymer and the MOF, but not the polymer-filler interface
      volume (so-called void volume). The sFFV for the MMM was calculated between 0.23
      cm3/g for a 24 wt % Al-fum/Matrimid MMM and 0.12 cm3/g for a 24 wt % Al
      fum(DMSO)/Matrimid MMM. The negligible effect of an interface volume is supported
      by a good matching of theoretical and experimental density of the Al-fum and Al
      fum/(DMSO) MMMs which gave a specific void volume below 0.02 cm3/g, often even
      below 0.01 cm3/g.

PMID- 30193061
TI  - A Markedly Improved Synthetic Approach for the Preparation of Multifunctional Au
      DNA Nanoparticle Conjugates Modified with Optical and MR Imaging Probes.
AB  - We describe a new, and vastly superior approach for labeling spherical nucleic
      acid conjugates (SNAs) with diagnostic probes. SNAs have been shown to provide
      the unique ability to traverse the cell membrane and deliver surface conjugated
      DNA into cells while preserving the DNA from nuclease degradation. Our previous
      work on preparing diagnostically labeled SNAs was labor intensive, relatively low
      yielding, and costly. Here, we describe a straightforward and facile preparation
      for labeling SNAs with optical and MR imaging probes with significantly improved
      physical properties. The synthesis of Gd(III) labeled DNA Au nanoparticle
      conjugates is achieved by sequential conjugation of 3'-thiol-modified
      oligonucleotides and cofunctionalization of the particle surface with the
      subsequent addition of 1,2 diothiolate modified chelates of Gd(III) (abbreviated:
      DNA-GdIII@AuNP). This new generation of SNA conjugates has a 2-fold increase of
      DNA labeling and a 1.4-fold increase in Gd(III) loading compared to published
      constructs. Furthermore, the relaxivity ( r1) is observed to increase 4.5-fold
      compared to the molecular dithiolane-Gd(III) complex, and 1.4-fold increase
      relative to previous particle constructs where the Gd(III) complexes were
      conjugated to the oligonucleotides rather than directly to the Au particle.
      Importantly, this simplified approach (2 steps) exploits the advantages of
      previous Gd(III) labeled SNA platforms; however, this new approach is scalable
      and eliminates modification of DNA for attaching the contrast agent, and the
      particles exhibit improved cell labeling.

PMID- 30193062
TI  - In Situ Electron Diffraction Tomography Using a Liquid-Electrochemical
      Transmission Electron Microscopy Cell for Crystal Structure Determination of
      Cathode Materials for Li-Ion batteries.
AB  - We demonstrate that changes in the unit cell structure of lithium battery cathode
      materials during electrochemical cycling in liquid electrolyte can be determined
      for particles of just a few hundred nanometers in size using in situ transmission
      electron microscopy (TEM). The atomic coordinates, site occupancies (including
      lithium occupancy), and cell parameters of the materials can all be reliably
      quantified. This was achieved using electron diffraction tomography (EDT) in a
      sealed electrochemical cell with conventional liquid electrolyte (LP30) and
      LiFePO4 crystals, which have a well-documented charged structure to use as
      reference. In situ EDT in a liquid environment cell provides a viable alternative
      to in situ X-ray and neutron diffraction experiments due to the more local
      character of TEM, allowing for single crystal diffraction data to be obtained
      from multiphased powder samples and from submicrometer- to nanometer-sized
      particles. EDT is the first in situ TEM technique to provide information at the
      unit cell level in the liquid environment of a commercial TEM electrochemical
      cell. Its application to a wide range of electrochemical experiments in liquid
      environment cells and diverse types of crystalline materials can be envisaged.

PMID- 30193063
TI  - Polarity-Tuning Derivatization-LC-MS Approach for Probing Global Carboxyl
      Containing Metabolites in Colorectal Cancer.
AB  - Carboxyl-containing metabolites (CCMs) widely exist in living systems and are the
      essential components for life. Global characteristics of CCMs in biological
      samples are critical for the understanding of physiological processes and the
      discovery for the onset of relevant diseases. However, their determination
      represents a challenge due to enormous polarity differences, structural
      diversity, high structural similarity, and poor ionization efficiency in mass
      spectrometry. Herein, 5-(diisopropylamino)amylamine (DIAAA) derivatization
      coupled with liquid chromatography-mass spectrometry (LC-MS) was developed for
      mapping the CCMs. With this methodology, the sensitivity was significantly
      enhanced. More importantly, the hydrophobicity of polar CCMs, amino acids, TCA
      cycle intermediates, and short-chain fatty acids and the hydrophilicity of low
      polar CCMs, long-chain fatty acids, and bile acids were significantly increased,
      resulting in a remarkable separation efficiency for which 68 CCMs can be
      simultaneously determined. Furthermore, the polarity-tuning effect was confirmed
      to be induced by the different impacts of aliphatic chains and nitrogen atom in
      DIAAA, the latter existing as a cation in the acidic mobile phase, using
      different derivatization reagents. Finally, this derivatization method was
      utilized to hunt for the potential biomarkers in colorectal cancer (CRC) patients
      and 52 CCMs, related with several key metabolic pathways, including amino acids
      metabolism, TCA cycle, fatty acid metabolism, pyruvate metabolism, and gut flora
      metabolism were identified. This innovative polarity-tuning derivatization-LC-MS
      approach was proved to be a valuable tool for probing global metabolome with high
      separation efficiency and sensitivity in various biological samples.

PMID- 30193064
TI  - Comprehensive Three-Dimensional LC * LC * Ion Mobility Spectrometry Separation
      Combined with High-Resolution MS for the Analysis of Complex Samples.
AB  - Comprehensive two-dimensional liquid chromatography (LC * LC) and ion mobility
      spectrometry-mass spectrometry (IMS-MS) are increasingly being used to address
      challenges associated with the analysis of highly complex samples. In this work,
      we evaluate the potential of the combination of these techniques in the form of a
      comprehensive three-dimensional LC * LC * IMS separation system. As application,
      hydrophilic interaction chromatography (HILIC) * reversed phase LC (RP-LC) * IMS
      high-resolution MS (HR-MS) was used to analyze a range of phenolic compounds,
      including hydrolyzable and condensed tannins, flavonoids, and phenolic acids in
      several natural products. A protocol for the extraction and visualization of the
      four-dimensional data obtained using this approach was developed. We show that
      the combination of HILIC, RP-LC, and IMS offers excellent separation of complex
      phenolic samples in three dimensions. Benefits associated with the incorporation
      of IMS include improved MS sensitivity and mass-spectral data quality. IMS also
      provided separation of trimeric procyanidin isomeric species that could not be
      differentiated by HILIC * RP-LC or HR-MS. On the traveling wave IMS (TWIMS)
      system used here, both IMS separation performance and the extent of second
      dimension (2D) undersampling depend on the upper mass scan limit, which might
      present a limitation for the analysis of larger molecular ions. The performance
      of the LC * LC * IMS system was characterized in terms of practical peak capacity
      and separation power, using established theory and taking undersampling and
      orthogonality into account. An average increase in separation performance by a
      factor of 13 was found for the samples analyzed here when IMS was incorporated
      into the HILIC * RP-LC-MS workflow.

PMID- 30193065
TI  - High-Throughput Screening of MOF Adsorbents and Membranes for H2 Purification and
      CO2 Capture.
AB  - Metal organic frameworks (MOFs) have emerged as great adsorbent and membrane
      candidates for separation of CO2/H2 mixtures. The main challenge is the existence
      of thousands of MOFs, which requires computational screening methods to identify
      the best materials prior to experimental efforts. In this study, we performed
      high-throughput computational screening of MOFs to examine their adsorbent and
      membrane performances for CO2/H2 separation. Grand canonical Monte Carlo (GCMC)
      and molecular dynamics (MD) simulations were used to compute various adsorbent
      and membrane performance metrics of 3857 MOFs. CO2/H2 adsorption selectivities of
      MOFs at pressure swing adsorption (PSA) and vacuum swing adsorption (VSA)
      conditions were calculated to be in the range of 2.5-25 000 and 2.5-85 000,
      respectively, outperforming many zeolite adsorbents. Correlations between the
      ranking of MOF adsorbents at the PSA and VSA conditions were examined. H2/CO2
      selectivities and H2 permeabilities of MOF membranes were computed as 2.1 * 10-5
      6.3 and 230-1.7 * 106 Barrer, respectively. A high number of MOF membranes was
      identified to surpass the upper bound defined for polymers due to high gas
      permeabilities of MOFs. Structure-performance relations revealed that MOFs with
      narrow pore sizes and low porosities are the best adsorbent materials for
      separation of CO2 from H2, whereas MOFs with large pore sizes and high porosities
      are the best membrane materials for selective separation of H2. Our results will
      guide the selection of MOF adsorbents and membranes for efficient H2 purification
      and CO2 capture processes.

PMID- 30193066
TI  - Insecticide Exposure and Development of Nonalcoholic Fatty Liver Disease.
AB  - Nonalcoholic fatty liver disease (NAFLD) is the prevalent liver disease resulting
      from metabolic disorder, which is highly associated with obesity and type 2
      diabetes. Emerging evidence has shown that insecticide exposure disrupts lipid
      and glucose metabolism and results in obesity and type 2 diabetes. However, the
      potential impact of insecticide exposure on the liver functions related to NAFLD
      development is largely unknown. Thus, this perspective focused on the current
      knowledge of the effect of insecticides on the liver functions, particularly
      lipid and glucose metabolism, as well as other liver functions to correlate
      insecticide exposure and the development of NAFLD.

PMID- 30193067
TI  - Triple-Indicator-Based Multidimensional Colorimetric Sensing Platform for Heavy
      Metal Ion Detections.
AB  - Heavy metals are highly toxic at trace levels and their pollution has shown great
      threat to the environment and public health worldwide where current detection
      methods require expensive instrumentation and laborious operation, which can only
      be accomplished in centralized laboratories. Herein, we report a low-cost, paper
      based microfluidic analytical device (MUPAD) for facile, portable, and disposable
      monitoring of mercury, lead, chromium, nickel, copper, and iron ions. Triple
      indicators or ligands that contain ions or molecules are preloaded on the MUPADs
      and upon addition of a metal ion, the colorimetric indicators will elicit color
      changes observed by the naked eyes. The color features were quantitatively
      analyzed in a three-dimensional space of red, green, and blue or the RGB-space
      using digital imaging and color calibration techniques. The sensing platform
      offers higher accuracy for cross references, and is capable of simultaneous
      detection and discrimination of different metal ions in even real water samples.
      It demonstrates great potential for semiquantitative and even qualitative
      analysis with a sensitivity below the safe limit concentrations, and a controlled
      error range.

PMID- 30193068
TI  - Sizable Excitonic Effects Undermining the Photocatalytic Efficiency of beta
      Cu2V2O7.
AB  - Copper vanadates have been proposed as promising photoanodes for water-splitting
      photoelectrochemical cells, but their performance has recently been shown to be
      severely limited. To understand this behavior, we study the electronic structure
      and the optical properties of beta-Cu2V2O7 both experimentally and
      computationally. The measured absorption spectrum shows an absorption peak at 1.5
      eV followed by the onset of an apparent continuum at 2.26 eV, as generally found
      for this class of materials. We perform calculations within the framework of the
      QS GW method and the Bethe-Salpeter equation while including effects of magnetic
      ordering, nuclear quantum motion, and thermal vibrations. We demonstrate the
      occurrence of two kinds of excitons with high binding energies upon optical
      excitation in beta-Cu2V2O7, which account for the first absorption peak and the
      lower edge of the apparent continuum. The results are confirmed by
      photoluminescence measurements, where sub-band-gap emissions are found for both
      excitons. These results provide an explanation for the low photocatalytic
      efficiencies of copper vanadates, despite the favorable size of their optical
      band gaps.

PMID- 30193069
TI  - Regain Strain-Hardening in High-Strength Metals by Nanofiller Incorporation at
      Grain Boundaries.
AB  - Grain refinement to the nano/ultrafine-grained regime can make metals several
      times stronger, but this process is usually accompanied by a dramatic loss of
      ductility. Such strength-ductility trade-off originates from a lack of strain
      hardening capacity in tiny grains. Here, we present a strategy to regain the
      strain-hardening ability of high-strength metals by incorporation of extrinsic
      nanofillers at grain boundaries. We demonstrate that the dislocation storage
      ability in Cu grains can be considerably improved through this novel grain
      boundary engineering approach, leading to a remarkably enhanced strain-hardening
      capacity and tensile ductility (uniform elongation). Experiments and large-scale
      atomistic simulations reveal that a key benefit of incorporated nanofillers is a
      reduction in the grain-boundary energy, enabling concurrent dislocation storage
      near the boundaries and in the Cu grain interior during straining. The strategy
      of grain-boundary engineering through nanofillers is easily controllable,
      generally applicable, and may open new avenues for producing nanostructured
      metals with extraordinary mechanical properties.

PMID- 30193070
TI  - Fate and Effect of Nano Tungsten Carbide Cobalt (WCCo) in the Soil Environment:
      Observing a Nanoparticle Specific Toxicity in Enchytraeus crypticus.
AB  - Tungsten carbide cobalt (WCCo) nanoparticles (NPs) are widely used in hard metal
      industries. Pulmonary diseases and risk of cancer are associated with
      occupational exposure, but knowledge about the environmental fate and effects is
      virtually absent. In this study, the fate and effects of crystalline WCCo NPs,
      WC, and Co2+ were assessed in the soil model Enchytraeus crypticus, following the
      standard Enchytraeid Reproduction Test (ERT). An additional 28 day exposure
      period compared to the ERT (i.e., a total of 56 days) was performed to assess
      longer-term effects. WCCo NPs affected reproduction at a concentration higher
      than the corresponding Co based (EC50 = 1500 mg WCCo/kg, equivalent to 128 mg
      Co/kg). WC showed no negative effect up to 1000 mg W/kg. Maximum uptake of Co was
      10-fold higher for CoCl2 compared to WCCo exposed organisms. Overall toxicity
      seems to be due to a combined effect between WC and Co. This is supported by the
      soil bioavailable fraction and biological tissue measurements. Last, results
      highlight the need to consider longer exposure period of NPs for comparable
      methods standardized for conventional chemicals.

PMID- 30193071
TI  - Evidence of Band-Edge Hole Levels Inversion in Spherical CuInS2 Quantum Dots.
AB  - CuInS2 (CIS) quantum dots (QDs) have emerged as one of the most promising
      candidates for application in a number of new technologies, mostly due to their
      heavy-metal-free composition and their unique optical properties. Among those,
      the large Stokes shift and the long-lived excited state are the most striking
      ones. Although these properties are important, the physical mechanism that
      originates them is still under debate. Here, we use two-photon absorption
      spectroscopy and ultrafast dynamics studies to investigate the physical origin of
      those phenomena. From the two-photon absorption spectroscopy, we observe yet
      another unique property of CIS QDs, a two-photon absorption transition below the
      one-photon absorption band edge, which has never been observed before for any
      other semiconductor nanostructure. This originates from the inversion of the 1S
      and 1P hole level order at the top of the valence band and results in a blue
      shift of the experimentally measured one photon absorption edge by nearly 100 to
      200 meV. However, this shift is not large enough to account for the Stokes shift
      observed, 200-500 meV. Consequently, despite the existence of the below band gap
      optical transition, photoluminescence in CIS QDs must originate from trap sites.
      These conclusions are reinforced by the multiexciton dynamics studies. From
      those, we demonstrate that biexciton Auger recombination behaves similarly to
      negative trion dynamics on these nanomaterials, which suggests that the trap
      state is an electron donating site.

PMID- 30193072
TI  - Photocatalysis and Hydrogen Evolution of Al- and Zn-Doped TiO2 Nanotubes
      Fabricated by Atomic Layer Deposition.
AB  - Highly homogeneous Al- and Zn-doped TiO2 nanotubes were fabricated by atomic
      layer deposition (ALD) via nanolaminated stacks of binary layers of TiO2/Al2O3
      and TiO2/ZnO, respectively. The bilayers were alternately deposited on the
      polycarbonate (PC) membrane template by ALD with various cyclic sequences. The
      nanotubes in a length of 20 MUm and a diameter of 220 nm were obtained after
      removal of the PC membrane by annealing at 450  degrees C. The effects of doping
      composition on the photocatalytic and photoelectrochemical (PEC) activities were
      investigated. Increasing the Al doping reduced the photocatalytic activity of
      TiO2 due to formation of charge recombination sites and reduction of hydroxide
      radicals. In contrast, there was an optimal range of Zn doping to get enhanced
      photocatalytic activity and higher PEC efficiency. With a doping ratio of 0.01,
      the hydrogen production rate from water splitting was 6 times higher than that of
      commercial P25 TiO2. The energy-band diagram of Zn-doped TiO2 determined by
      ultraviolet photoelectron spectroscopy revealed shift up of the Fermi level to
      provide more electrons to the conduction band. The photoinduced trapped electrons
      and holes were detected in Zn-doped TiO2 by in situ electron paramagnetic
      resonance spectroscopy, which revealed that Ti3+ sites on the surface and surface
      oxygen vacancies played a key role in promoting the photocatalytic process.

PMID- 30193073
TI  - Bilateral Panuveitis and Keratitis as First Presentation of Relapsing
      Polychondritis.
AB  - PURPOSE: To report a rare case of relapsing polychondritis with bilateral
      panuveitis as the first presentation of systemic disease Methods: A 26-year-old
      female presented with bilateral decreased vision, red eye and ocular pain
      underwent complete ocular examination, retinal imaging and systemic
      investigation. RESULTS: Investigations revealed bilateral panuveitis associated
      with keratitis, retinal hemorrhages and retinal vasculitis. Following systemic
      work-ups and the pinna cartilage biopsy, diagnosis of relapsing polychondritis
      was made. CONCLUSION: Owing to debilitating and even life-threatening
      consequences of enigmatic relapsing polychondritis, high suspicion of the disease
      is of paramount importance in cases of retinal vasculitis and uveitis.

PMID- 30193074
TI  - Effects of basketball-specific high-intensity interval training on aerobic
      performance and physical capacities in youth female basketball players.
AB  - OBJECTIVE: The goal of this study was to investigate the effects of a 5-week,
      basketball-specific high-intensity interval training (HIIT) on aerobic
      performance in youth female basketball players. METHODS: Twenty-four athletes
      (age 15.1 +/- 1.1 years; height: 170 +/- 5.2 cm; body mass: 60.9 +/- 6.0 kg) took
      part in the investigation. The training group (TG, n = 11) integrated 10
      basketball-specific HIIT sessions in their normal team training, the other group
      (n = 13) continued their team training routine and served as controls (CG). All
      HIIT sessions contained different basketball-specific drills. Before (pre-) and
      after the training period (post-) physical fitness was tested. RESULTS: The Yo-yo
      intermittent recovery test (Yo-yo IR) performance was very likely increased in
      the TG (26,5 %). No improvements in the Yo-Yo IR performance were found in the CG
      (-6,8%). Likely positive effects in the TG were evident for the sprint and
      agility tests with (1.2 +/- 2.4%, ES: 0.25, p = 0.29) and without ball (1.5 +/-
      4.6%, ES: 0.34, p = 0.20). The sprint and agility performance with ball
      significantly decreased in the CG by -2.8 +/- 4.7% (ES: 0.49, p < 0.01). No
      differences between the groups were found for counter movement jump with arm
      swing (TG: ES = 0.14, p = 0.45, CG: ES = 0.20 p = 0.18), counter movement jump
      (TG: ES = 0.05, p = 0.70, CG: ES = 0.19, p = 0.10), squat jump (TG: ES = 0.06, p
      = 0.72, CG: ES = 0.10, p = 0.54) and long jump (TG: ES = 0.00, p = 0.82, CG: ES =
      0.00, p = 0.81). CONCLUSION: A 5-week, basketball-specific HIIT improves the
      aerobic performance in young female basketball athletes.

PMID- 30193075
TI  - Developing a bilingual mobile dictionary for Indian Sign Language and gathering
      users experience with SignDict.
AB  - Availability of a sign language dictionary is very important for the literacy of
      deaf people. But the intricacies involved in the representation of the sign
      language impede attempts at representing it in a printed format. A video-based
      solution helps to solve this problem. This article discusses the development of a
      bilingual mobile sign language dictionary which has features for converting
      camera-captured text into sign language and translating simple sentences from a
      spoken language into their corresponding signs. Feedback from 2,900 users spread
      across India who have installed our mobile application indicates that users
      prefer mobile application for learning Indian Sign Language (ISL). Comparing the
      existing printed sign language dictionaries and other mobile-based ISL
      dictionaries with the mobile application we have developed, 45 stakeholders of a
      deaf school assessed that its features like easy availability, speed of
      operation, and character recognition are very effective in learning ISL.

PMID- 30193076
TI  - A crosslinked and ribosylated actin trimer does not interact productively with
      myosin.
AB  - A purified F-actin derived actin trimer that interacts with end-binding proteins
      did not activate or bind the side-binding protein myosin under rigor conditions.
      Remodeling of the actin trimer by the binding of gelsolin did not rescue myosin
      binding, nor did the use of different means of inhibiting the polymerization of
      the trimer. Our results demonstrate that ADP-ribosylation on all actin subunits
      of an F-actin derived trimer inhibits myosin binding and that the binding of
      DNase-I to the pointed end subunits of a crosslinked trimer also remodels the
      myosin binding site. Taken together, this work highlights the need for a careful
      balance between modification of actin subunits and maintaining protein-protein
      interactions to produce a physiologically-relevant short F-actin complex.

PMID- 30193077
TI  - Retrospective analysis of coronary interventions in a single centre and
      comparison of specific differences between radial and femoral access.
AB  - OBJECTIVES: The aim of this study was to analyse the consequence of radial or
      femoral access during coronary interventions to radiation dose, fluorography time
      and a number of pseudoaneurysms following each type of intervention. BACKGROUND:
      According to the results of many recent studies (RIVAL, RIFLE-STEACS, STEMI
      RADIAL), current guidelines favour radial over femoral access during coronary
      intervention for safety, especially in cases of acute coronary syndromes.
      However, several papers have referred to problems in the design of these studies
      and the management of antithrombotic therapy. The influence of access site on
      radiation dose and fluorography time is also still unclear. METHODS: We
      retrospectively analysed 4522 patients who underwent coronary angiography in 2012
      and 2016 in a single centre in the Czech Republic. We compared the access site
      with the average radiation dose and mean effective dose that each patient
      received in Gy/cm2 or mSv, respectively. We also compared average fluorography
      time in minutes and the incidence of pseudoaneurysms. RESULTS: The radiation dose
      was a body mass index (BMI)-dependent parameter since each five points of body
      mass index increased radiation dose approximately by 23%. Use of femoral access
      resulted in lower fluorography time in all subgroups (p < .001) and decreased
      radiation dose in patients with coronary artery bypass grafts (CABGs) by 26% (p =
      .044). On the other hand, there has been 16 times lower frequency (p < .001) of
      post-catheterisation pseudoaneurysms after radial access than after femoral
      access. CONCLUSIONS: Both the radiation dose and fluorography time were lower
      after femoral access compared to radial access in patients with CABGs. On the
      other hand, radial access led to significantly fewer periprocedural
      pseudoaneurysms. Radial access therefore should be considered as the preferred
      access site during coronary intervention in patients with a high risk of
      pseudoaneurysm development, and femoral access should be considered for patients
      with a high risk of contrast-induced nephropathy.

PMID- 30193078
TI  - Moderate to vigorous physical activity and impact loading independently predict
      variance in bone strength at the tibia but not at the radius in children.
AB  - OBJECTIVES: To assess if daily minutes of moderate-to-vigorous physical activity
      (MVPA) or vigorous physical activity (VPA) and impact counts (acceleration peaks
      >=3.9g) would independently predict variance in bone strength in children and
      youth. Second, to estimate bone strength gain associated with increases in daily
      MVPA, VPA or impact counts. METHODS: We recorded 7-day activity of 49
      participants, mean age 11.0; SD 1.7 years, using accelerometers and estimated
      radius and tibia bone strength using peripheral quantitative computed tomography.
      We used linear regression models adjusted for sex, body mass and muscle area to
      address objectives. RESULTS: Daily MVPA (mean 50, SD 23 min) and VPA (17, 11) or
      impacts (71, 59 counts) did not predict variance in radius strength. Daily VPA
      (beta=0.24), predicted variance in tibia strength at the distal and shaft sites,
      shaft strength was also predicted by MVPA (beta=0.20) and impact counts
      (beta=0.21). Our models estimated a 3-6%, 4%, and 4-11% gain in tibia strength
      after increasing daily MVPA by 10-20 min, VPA by 5 min, or impacts by 30-100
      counts, respectively. CONCLUSIONS: Daily minutes MVPA, VPA and impact counts were
      independent predictors of tibia but not radius strength. Objective recording of
      activities associated with forearm bone strength and trials testing efficacy of
      increasing daily MVPA, VPA and related impacts on bone strength development in
      children and youth are warranted.

PMID- 30193079
TI  - Increased cancer incidence in Holocaust survivors and the implications for
      survivors of other extreme events.

PMID- 30193080
TI  - Is There a Pathological Gait Associated With Common Soft Tissue Running Injuries?
AB  - BACKGROUND: Previous research has demonstrated clear associations between
      specific running injuries and patterns of lower limb kinematics. However, there
      has been minimal research investigating whether the same kinematic patterns could
      underlie multiple different soft tissue running injuries. If they do, such
      kinematic patterns could be considered global contributors to running injuries.
      HYPOTHESIS: Injured runners will demonstrate differences in running kinematics
      when compared with injury-free controls. These kinematic patterns will be
      consistent among injured subgroups. STUDY DESIGN: Controlled laboratory study.
      METHODS: The authors studied 72 injured runners and 36 healthy controls. The
      injured group contained 4 subgroups of runners with either patellofemoral pain,
      iliotibial band syndrome, medial tibial stress syndrome, or Achilles tendinopathy
      (n = 18 each). Three-dimensional running kinematics were compared between injured
      and healthy runners and then between the 4 injured subgroups. A logistic
      regression model was used to determine which parameters could be used to identify
      injured runners. RESULTS: The injured runners demonstrated greater contralateral
      pelvic drop (CPD) and forward trunk lean at midstance and a more extended knee
      and dorsiflexed ankle at initial contact. The subgroup analysis of variance found
      that these kinematic patterns were consistent across each of the 4 injured
      subgroups. CPD was found to be the most important variable predicting the
      classification of participants as healthy or injured. Importantly, for every 1
      degrees  increase in pelvic drop, there was an 80% increase in the odds of being
      classified as injured. CONCLUSION: This study identified a number of global
      kinematic contributors to common running injuries. In particular, we found
      injured runners to run with greater peak CPD and trunk forward lean as well as an
      extended knee and dorsiflexed ankle at initial contact. CPD appears to be the
      variable most strongly associated with common running-related injuries. CLINICAL
      RELEVANCE: The identified kinematic patterns may prove beneficial for clinicians
      when assessing for biomechanical contributors to running injuries.

PMID- 30193082
TI  - Removal of acetone from air emissions by biotrickling filters: providing
      solutions from laboratory to full-scale.
AB  - A full-scale biotrickling filter (BTF) treating acetone air emissions of wood
      coating activities showed difficulties to achieve outlet concentrations lower
      than 125 mg C m-3, especially for high inlet concentrations and oscillating
      emissions. To solve this problem, a laboratory investigation on acetone removal
      was carried out simulating typical industrial conditions: discontinuous and
      variable inlet concentrations and intermittent spraying. The results were
      evaluated in terms of removal efficiency and outlet gas emission pattern.
      Industrial emissions and operational protocols were simulated: inlet load up to
      70 g C m-3 h-1 during 2 cycles of 4 h per day and intermittent trickling of 15
      min per hour. The outlet gas stream of the pollutant was affected by intermittent
      spraying, causing a fugitive emission of pollutant. Complete removal efficiency
      was obtained during non-spraying. Average removal efficiencies higher than 85%
      were obtained, showing the feasibility of BTF to treat acetone. The outlet gas
      stream showed a clear dependence on the pH of the trickling liquid, decreasing
      the removal at pH < 5.5. Thus, a proper control of alkalinity, with regular
      NaHCO3 addition, was required for successful operation. The laboratory findings
      were fruitfully transferred to the industry, and the removal of acetone by full
      scale BTF was improved.

PMID- 30193081
TI  - Fecal fat and energy loss in pancreas exocrine insufficiency: the role of
      pancreas enzyme replacement therapy.
AB  - BACKGROUND: Chronic pancreatitis (CP) can lead to severe pancreatic exocrine
      insufficiency (PEI). Pancreatic enzyme replacement therapy (PERT) is well
      established, but knowledge of the physiological response to increasing doses on
      fecal fat- and energy loss is scarce. METHODS: We included 10 patients with CP
      and established PEI and 12 healthy controls for a prospective interventional
      study. Subjects received no PERT in the first week followed by four weeks PERT
      incrementally increasing doses every week. For each week, three-day stool
      collection followed three days registration of nutritional intake. We measured
      the fecal output of fat and energy by van de Kamer titration and decomposition
      vessel calorimetry, respectively. We calculated fecal fat- and energy loss per
      day, the coefficient of fat absorption (CFA) and coefficient of energy absorption
      (CEA). RESULTS: Without PERT treatment, CP patients with PEI had significantly
      higher daily fecal fat and energy loss (p = .022; p = .035) compared to HC. In CP
      patients, there was a significant reduction of fecal fat and energy loss (p =
      .045; p = .037) when PERT doses reached maximum intake of 75,000 units per meal.
      In CP patients, there was a strong positive correlation between fecal loss of
      energy and fat (r = 0.99), and between fecal loss of energy and daily stool
      weight (r = 0.97). CFA and CEA correlated negatively with daily fecal fat loss (r
      = -0.72) and fecal energy loss (r = -0.65). CONCLUSIONS: PERT reduces fecal
      energy and fat loss in patients with CP and PEI. Fecal energy loss in CP patients
      is strongly dependent on fecal fat loss, and on fecal weight.

PMID- 30193083
TI  - Greater Laxity in the Anterior Cruciate Ligament-Injured Knee Carries a Higher
      Risk of Postreconstruction Pivot Shift: Intraoperative Measurements With a
      Navigation System.
AB  - BACKGROUND: The presence of pivot shift after anterior cruciate ligament (ACL)
      reconstruction is correlated with worse clinical outcomes. An orthopaedic
      navigation system is a useful tool for quantifying laxity in the ACL-deficient
      knee. PURPOSE: To investigate the relationship between preoperative knee laxity
      measured by a navigation system and postoperative pivot shift (PPS) after ACL
      reconstruction. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS:
      One hundred patients who underwent primary ACL reconstruction (62 hamstring
      tendon grafts, 38 patellar tendon grafts) were grouped according to the presence
      or absence of pivot shift at the 2-year follow-up, and the groups were compared
      retrospectively. Before surgery, knee laxity was assessed with a navigation
      system to quantify posterior tibial reduction (PTR) during pivot-shift tests and
      anterior tibial translation (ATT) during Lachman tests. PTR and ATT cutoff values
      were determined by receiver operator characteristic (ROC) analysis. RESULTS:
      Preoperative PTR and ATT were significantly larger for patients with PPS (PPS
      positive group) than those without (PPS-negative group). In the ROC analysis, the
      PTR had an area under the curve of 0.871 (95% CI, 0.763-0.979; P < .0001) for
      predicting a PPS; this was larger than that obtained for the ATT, which had an
      area under the curve of 0.825 (95% CI, 0.705-0.946; P = .001). Because the ROC
      curve of the ATT had 2 peaks, the ATT alone was not a suitable predictor for PPS.
      Based on the ROC curve, the optimal PTR cutoff value was 7 mm, with 88.9%
      sensitivity and 71.4% specificity for PPS (adjusted odds ratio = 19.7; 95% CI,
      2.1-187.9; P = .009). Setting the cutoff value as a combination of the PTR (?7
      mm) and ATT (?12 mm) improved the specificity (88.9% sensitivity and 84.6%
      specificity; adjusted odds ratio = 149.8; 95% CI, 5.9-3822.7; P = .002) over that
      with the PTR alone. CONCLUSION: ACL injuries in knees with a large PTR had a
      higher risk of PPS. When reconstructing the ACL in a knee with a high degree of
      laxity, surgeons may need to adopt strategies to prevent PPS.

PMID- 30193084
TI  - Exogenous putrescine affects polyamine and arginine metabolism in rat liver
      following bile ductus ligation.
AB  - Rat bile duct ligation (BDL) represents a useful method that mimics obstructive
      extrahepatic cholestasis, which is known to be a frequent disorder in humans.
      Polyamines (putrescine, spermidine, and spermine) are one of the key molecules
      regulating cell proliferation and differentiation. This work aimed to evaluate
      the potential beneficial properties of putrescine in rat BDL model by studying
      several biochemical parameters reflecting liver function and polyamine
      metabolism. Rats that were subjected to BDL were injected with putrescine (150
      mg/kg) for 9 days, while in parallel another group with BDL remained untreated.
      Two control groups were included as well, sham-opened and putrescine-treated
      group. The following plasma parameters: ALT, AST, gamma-GT, ALP, bilirubin, bile
      acids, as well as liver malondialdehyde and polyamine concentration and the
      activity of enzymes involved in polyamine metabolism were studied. After BDL,
      significant alterations in plasma biochemical parameters occurred, where a 9-day
      putrescine treatment significantly alleviated liver function deterioration.
      Putrescine also increased liver polyamines' concentrations and polyamine and
      diamine oxidase activities in rats submitted to BDL. Our results demonstrated,
      for the first time, that putrescine plays an important role in preserving liver
      tissue function in rats with experimentally induced cholestasis.

PMID- 30193085
TI  - Moxifloxacin-induced QT interval prolongation and torsades de pointes: a
      narrative review.
AB  - INTRODUCTION: Moxifloxacin is widely used for the treatment of a number of
      infectious diseases because of its favorable pharmacological profile and high
      clinical success rate. However, it is often criticized for its higher risk of QTc
      interval prolongation (QTIP) and torsades de pointes (TdP). Areas covered: A
      review of published literature on moxifloxacin-related QTIP and TdP. Readers will
      be provided with a comprehensive overview of the prevalence, cellular mechanism,
      risk factors, and magnitude of QTIP of moxifloxacin. Expert commentary: In
      healthy subjects, moxifloxacin prolongs the QTc interval by 11.5-19.5 ms, it
      binds at the Tyr652 residue in the S6 pore domain of the human ether a-go-go gene
      related potassium channel. Considerable QTIP (30-60 ms) have also been reported
      in some patients, for instance the incidence of QTIP (30-60 ms) in elderly
      pneumonia patients was 15.5%. Moxifloxacin-induced QTIP may be of little clinical
      importance in healthy individuals. However, marked QTIP (>60 ms) and TdP have
      been reported in high-risk patients (patients who have multiple QT prolonging
      risk factors). Patients must be thoroughly assessed prior to the use of
      moxifloxacin and high-risk patients must be identified using risk assessment
      tools to ensure safe use of moxifloxacin and to safeguard patients' health.

PMID- 30193086
TI  - In vitro evaluation of dual-antigenic PV1 peptide vaccine in head and neck cancer
      patients.
AB  - Peptide vaccines derived from tumour-associated antigens have been used as an
      immunotherapeutic approach to induce specific cytotoxic immune response against
      tumour. We previously identified that MAGED4B and FJX1 proteins are overexpressed
      in HNSCC patients; and further demonstrated that two HLA-A2-restricted 9-11 amino
      acid peptides derived from these proteins were able to induce anti-tumour immune
      responses in vitro independently using PBMCs isolated from these patients. In
      this study, we evaluated the immunogenicity and efficacy of a dual-antigenic
      peptide vaccine (PV1), comprised of MAGED4B and FJX1 peptides in HNSCC patients.
      We first demonstrated that 94.8% of HNSCC patients expressed MAGED4B and/or FJX1
      by immunohistochemistry, suggesting that PV1 could benefit the majority of HNSCC
      patients. The presence of pre-existing MAGED4B and FJX1-specific T-cells was
      detected using a HLA-A2 dimer assay and efficacy of PV1 to induce T-cell to
      secrete cytotoxic cytokine was evaluated using ELISPOT assay. Pre-existing PV1
      specific T-cells were detected in all patients. Notably, we demonstrated that
      patients' T-cells were able to secrete cytotoxic cytokines upon exposure to
      target cells expressing the respective antigen post PV1 stimulation. Furthermore,
      patients with high expression of MAGED4B and FJX1 in their tumours were more
      responsive to PV1 stimulation, demonstrating the specificity of the PV1 peptide
      vaccine. Additionally, we also demonstrated the expression of MAGED4B and FJX1 in
      breast, lung, colon, prostate and rectal cancer suggesting the potential use of
      PV1 in these cancers. In summary, PV1 could be a good vaccine candidate for the
      treatment of HNSCC patients and other cancers expressing these antigens.

PMID- 30193088
TI  - Identifying determinants of noise in a medical intensive care unit.
AB  - Continuous and intermittent exposure to noise elevates stress, increases blood
      pressure, and disrupts sleep among patients in hospital intensive care units. The
      purpose of this study was to determine the effectiveness of a behavior-based
      intervention to reduce noise and to identify determinants of noise in a medical
      intensive care unit. Staff were trained for six weeks to reduce noise during
      their activities in an effort to keep noise levels below 55 dBA during the day
      and below 50 dBA at night. One-min noise levels were logged continuously in
      patient rooms eight weeks before and after the intervention. Noise levels were
      compared by room position, occupancy status, and time of day. Noise levels from
      flagged days (>60 dBA for >10 hrs) were correlated with activity logs. The
      intervention was ineffective with noise frequently exceeding project goals during
      the day and night. Noise levels were higher in rooms with the oldest heating,
      ventilation, and air-conditioning system, even when patient rooms were
      unoccupied. Of the flagged days, the odds of noise over 60 dBA occurring was 5.3
      higher when high-flow respiratory support devices were in use compared to times
      with low-flow devices in use (OR= 5.3, 95% CI = 5.0 - 5.5). General sources, like
      the heating, ventilation, and air-conditioning system, contribute to high
      baseline noise and high-volume (>10 L/min) respiratory-support devices generate
      additional high noise (>60 dBA) in Intensive Care Unit patient rooms. This work
      suggests that engineering controls (e.g., ventilation changes or equipment
      shielding) may be more effective in reducing noise in hospital intensive care
      units than behavior modification alone.

PMID- 30193087
TI  - Effect of High-Grade Preoperative Knee Laxity on 6-Year Anterior Cruciate
      Ligament Reconstruction Outcomes.
AB  - BACKGROUND: Knee laxity in the setting of anterior cruciate ligament (ACL) injury
      is often assessed through physical examination using the Lachman, pivot shift,
      and anterior drawer tests. The degree of laxity noted on these examinations may
      influence treatment decisions and prognosis. HYPOTHESIS: Increased preoperative
      knee laxity is associated with increased risk of revision ACL reconstruction,
      increased risk of contralateral ACL reconstruction, and poorer patient-reported
      outcomes at 6 years postoperatively. STUDY DESIGN: Cohort study; Level of
      evidence, 2. METHODS: 2333 patients who underwent primary isolated ACL
      reconstruction without additional ligament injury were identified. Patients
      reported by the operating surgeons to have an International Knee Documentation
      Committee (IKDC) grade D Lachman, anterior drawer, or pivot shift examination
      were classified as having a high-grade laxity. Multiple logistic regression
      models were used to evaluate whether having high-grade preoperative laxity was
      predictive of increased odds of undergoing subsequent revision or contralateral
      ACL reconstruction within 6 years of the index procedure, controlling for patient
      age, sex, body mass index, Marx activity level, sport, graft type, medial
      meniscal treatment, and lateral meniscal treatment. Multiple linear regression
      modeling was used to evaluate whether having high-grade preoperative laxity was
      predictive of poorer IKDC or Knee injury and Osteoarthritis Outcome Score Knee
      Related Quality of Life (KOOS-QOL) scores at 6 years postoperatively, after
      controlling for baseline score, patient age, ethnicity, sex, body mass index,
      marital status, smoking status, sport participation, competition level, Marx
      activity rating score, graft type, and articular cartilage and meniscal status.
      RESULTS: In total, 743 of 2325 patients (32.0%) were noted to have high-grade
      laxity on at least 1 physical examination test. High-grade Lachman was noted in
      334 patients (14.4%), high-grade pivot shift was noted in 617 patients (26.5%),
      and high-grade anterior drawer was noted in 233 patients (10.0%). Six-year
      revision and contralateral ACL reconstruction data were available for 2129
      patients (91.6%). High-grade prereconstruction Lachman was associated with
      significantly increased odds of ACL graft revision (odds ratio [OR], 1.76; 95%
      CI, 1.10-2.80, P = .02) and contralateral ACL reconstruction (OR, 1.68; 95% CI,
      1.09-2.69; P = .019). High-grade prereconstruction pivot shift was associated
      with significantly increased odds of ACL graft revision (OR, 1.75; 95% CI, 1.19
      2.54, P = .002) but not with significantly increased odds of contralateral ACL
      reconstruction (OR, 1.30; 95% CI, 0.89-1.87; P = .16). High-grade
      prereconstruction laxity was associated with statistically significantly lower 6
      year IKDC (beta = -2.26, P = .003), KOOS-QOL (beta = -2.67, P = .015), and Marx
      activity scores (beta = -0.54, P = .020), but these differences did not approach
      clinically relevant differences in patient-reported outcomes. CONCLUSION: High
      grade preoperative knee laxity is predictive of increased odds of revision ACL
      reconstruction and contralateral ACL reconstruction 6 years after ACL
      reconstruction. Poorer patient-reported outcome scores in the high-grade laxity
      group were also noted, but the difference did not reach a level of clinical
      relevance.

PMID- 30193089
TI  - Editorial Comment.

PMID- 30193090
TI  - Editorial Comment.

PMID- 30193091
TI  - Editorial Comment.

PMID- 30193093
TI  - Set Phasers to Cleave: PIWI Cleavage Directs All piRNA Biogenesis.
AB  - In this issue of Molecular Cell, Gainetdinov et al. (2018) show that PIWI
      proteins direct both piRNA biogenesis and piRNA function in most animals.

PMID- 30193092
TI  - Pour Some Sugar on TDP(-43).
AB  - In this issue of Molecular Cell, McGurk et al. (2018) identify how poly(ADP
      ribose) binding tunes the phase behavior of the ALS disease protein TDP-43,
      uncovering the molecular events underlying its aggregation in disease and
      illuminating a novel therapeutic target.

PMID- 30193094
TI  - Structural Basis for Regulation of Phosphoinositide Kinases and Their Involvement
      in Human Disease.
AB  - Lipid phosphoinositides play fundamental roles in virtually all pathways that
      control a cell's decision to grow, move, divide, and die. Because of this,
      kinases that phosphorylate phosphoinositide lipids are critically involved in
      myriad essential functions including growth, development, and membrane
      trafficking. The misregulation of phosphoinositide kinases is critical in human
      diseases, including cancer, primary immunodeficiencies, and developmental
      disorders. Phosphoinositide kinases also play a role in mediating bacterial and
      viral infections for many potent human pathogens. Furthermore, inhibitors of
      parasite phosphoinositide kinases are in development as therapies for both
      malaria and cryptosporidiosis. Therefore, understanding how phosphoinositide
      kinases are regulated has implications for the treatment of many devastating
      human diseases. Recent structures of phosphoinositide kinases have revealed
      unique molecular insight into their regulation. This review will summarize our
      current molecular knowledge on phosphoinositide kinase regulation, and how this
      information is being used to generate novel small molecule inhibitors as
      potential therapeutics.

PMID- 30193095
TI  - mHTT Seeding Activity: A Marker of Disease Progression and Neurotoxicity in
      Models of Huntington's Disease.
AB  - Self-propagating, amyloidogenic mutant huntingtin (mHTT) aggregates may drive
      progression of Huntington's disease (HD). Here, we report the development of a
      FRET-based mHTT aggregate seeding (FRASE) assay that enables the quantification
      of mHTT seeding activity (HSA) in complex biosamples from HD patients and disease
      models. Application of the FRASE assay revealed HSA in brain homogenates of
      presymptomatic HD transgenic and knockin mice and its progressive increase with
      phenotypic changes, suggesting that HSA quantitatively tracks disease
      progression. Biochemical investigations of mouse brain homogenates demonstrated
      that small, rather than large, mHTT structures are responsible for the HSA
      measured in FRASE assays. Finally, we assessed the neurotoxicity of mHTT seeds in
      an inducible Drosophila model transgenic for HTTex1. We found a strong
      correlation between the HSA measured in adult neurons and the increased mortality
      of transgenic HD flies, indicating that FRASE assays detect disease-relevant,
      neurotoxic, mHTT structures with severe phenotypic consequences in vivo.

PMID- 30193096
TI  - Hsp90 Mediates Membrane Deformation and Exosome Release.
AB  - Hsp90 is an essential chaperone that guards proteome integrity and amounts to 2%
      of cellular protein. We now find that Hsp90 also has the ability to directly
      interact with and deform membranes via an evolutionarily conserved amphipathic
      helix. Using a new cell-free system and in vivo measurements, we show this
      amphipathic helix allows exosome release by promoting the fusion of
      multivesicular bodies (MVBs) with the plasma membrane. We dissect the
      relationship between Hsp90 conformation and membrane-deforming function and show
      that mutations and drugs that stabilize the open Hsp90 dimer expose the helix and
      allow MVB fusion, while these effects are blocked by the closed state. Hence, we
      structurally separated the Hsp90 membrane-deforming function from its well
      characterized chaperone activity, and we show that this previously unrecognized
      function is required for exosome release.

PMID- 30193097
TI  - Dynamic Acetylation of Phosphoenolpyruvate Carboxykinase Toggles Enzyme Activity
      between Gluconeogenic and Anaplerotic Reactions.
AB  - Cytosolic phosphoenolpyruvate carboxykinase (PCK1) is considered a gluconeogenic
      enzyme; however, its metabolic functions and regulatory mechanisms beyond
      gluconeogenesis are poorly understood. Here, we describe that dynamic acetylation
      of PCK1 interconverts the enzyme between gluconeogenic and anaplerotic
      activities. Under high glucose, p300-dependent hyperacetylation of PCK1 did not
      lead to protein degradation but instead increased the ability of PCK1 to perform
      the anaplerotic reaction, converting phosphoenolpyruvate to oxaloacetate. Lys91
      acetylation destabilizes the active site of PCK1 and favors the reverse reaction.
      At low energy input, we demonstrate that SIRT1 deacetylates PCK1 and fully
      restores the gluconeogenic ability of PCK1. Additionally, we found that GSK3beta
      mediated phosphorylation of PCK1 decreases acetylation and increases
      ubiquitination. Biochemical evidence suggests that serine phosphorylation
      adjacent to Lys91 stimulates SIRT1-dependent deacetylation of PCK1. This work
      reveals an unexpected capacity of hyperacetylated PCK1 to promote anaplerotic
      activity, and the intersection of post-translational control of PCK1 involving
      acetylation, phosphorylation, and ubiquitination.

PMID- 30193098
TI  - Non-canonical Activation of the DNA Sensing Adaptor STING by ATM and IFI16
      Mediates NF-kappaB Signaling after Nuclear DNA Damage.
AB  - DNA damage can be sensed as a danger-associated molecular pattern by the innate
      immune system. Here we find that keratinocytes and other human cells mount an
      innate immune response within hours of etoposide-induced DNA damage, which
      involves the DNA sensing adaptor STING but is independent of the cytosolic DNA
      receptor cGAS. This non-canonical activation of STING is mediated by the DNA
      binding protein IFI16, together with the DNA damage response factors ATM and PARP
      1, resulting in the assembly of an alternative STING signaling complex that
      includes the tumor suppressor p53 and the E3 ubiquitin ligase TRAF6. TRAF6
      catalyzes the formation of K63-linked ubiquitin chains on STING, leading to the
      activation of the transcription factor NF-kappaB and the induction of an
      alternative STING-dependent gene expression program. We propose that STING acts
      as a signaling hub that coordinates a transcriptional response depending on its
      mode of activation.

PMID- 30193100
TI  - The Akt-SRPK-SR Axis Constitutes a Major Pathway in Transducing EGF Signaling to
      Regulate Alternative Splicing in the Nucleus.

PMID- 30193099
TI  - A Single Mechanism of Biogenesis, Initiated and Directed by PIWI Proteins,
      Explains piRNA Production in Most Animals.
AB  - In animals, PIWI-interacting RNAs (piRNAs) guide PIWI proteins to silence
      transposons and regulate gene expression. The mechanisms for making piRNAs have
      been proposed to differ among cell types, tissues, and animals. Our data instead
      suggest a single model that explains piRNA production in most animals. piRNAs
      initiate piRNA production by guiding PIWI proteins to slice precursor
      transcripts. Next, PIWI proteins direct the stepwise fragmentation of the sliced
      precursor transcripts, yielding tail-to-head strings of phased precursor piRNAs
      (pre-piRNAs). Our analyses detect evidence for this piRNA biogenesis strategy
      across an evolutionarily broad range of animals, including humans. Thus, PIWI
      proteins initiate and sustain piRNA biogenesis by the same mechanism in species
      whose last common ancestor predates the branching of most animal lineages. The
      unified model places PIWI-clade Argonautes at the center of piRNA biology and
      suggests that the ancestral animal-the Urmetazoan-used PIWI proteins both to
      generate piRNA guides and to execute piRNA function.

PMID- 30193101
TI  - Separating Actin-Dependent Chemokine Receptor Nanoclustering from Dimerization
      Indicates a Role for Clustering in CXCR4 Signaling and Function.

PMID- 30193103
TI  - Body Art Gets Smart.

PMID- 30193102
TI  - A Systematic p53 Mutation Library Links Differential Functional Impact to Cancer
      Mutation Pattern and Evolutionary Conservation.

PMID- 30193104
TI  - Take a Deep Breath and Switch.
AB  - Choosing a research topic is an important decision at any level. The choice
      shapes decisions about what graduate lab to join, which post-doctoral position to
      pursue, how to start an independent lab, and what companies might make good
      employers. The thing to remember is that "the choice" can, and perhaps should, be
      made many times during a career, and each time, it can take an exciting new turn.
      Lara Szewczak sat down with Amy Gladfelter and Tony Hyman to talk about what it
      takes for a researcher to pivot-to decide that they want to embark on a new line
      of research. What does it mean at different points in a career, and how can you
      motivate colleagues to follow? Annotated excerpts from this conversation are
      presented below, and the full conversation is available with the article online.

PMID- 30193105
TI  - La Dolce Vita of Neurexin: Synaptic Partnerships through Glycosaminoglycans.
AB  - Various neurexin transcripts are thought to serve as presynaptic "hub" molecules
      by binding to their specific synaptic partners. In this issue, Zhang et al.
      demonstrate that neurexins are heparan sulfate (HS) proteoglycans and that the HS
      modification is important for synaptic function in vitro and in vivo. These
      findings open up the possibility of many more binding partners for the neurexins.

PMID- 30193106
TI  - Tuning Apoptosis and Neuroinflammation: TBK1 Restrains RIPK1.
AB  - Partial loss of TANK-binding kinase 1 (TBK1) causes amyotrophic lateral sclerosis
      (ALS) and frontotemporal dementia (FTD). Xu et al. identify the role of TBK1 in
      suppressing neuroinflammation and apoptosis by its inhibition of the receptor
      interacting serine/threonine-protein kinase 1 (RIPK1) and elucidate how aging and
      genetic susceptibility together cause neuroinflammation.

PMID- 30193107
TI  - Freeing Yeast from Alcohol Addiction (Just) to Make (It) Fat Instead.
AB  - Synthetically re-designing eukaryotic metabolism has proven immensely
      challenging, raising the question of whether evolution has metabolically
      hardwired eukaryotic cells. Yu et al. now report that, through orchestrating
      multiple genetic changes and laboratory evolution, Saccharomyces metabolism can
      be reprogrammed from its evolutionary objective of producing ethanol to produce
      large amounts of free fatty acids.

PMID- 30193108
TI  - Metabolic Frugality Marks Cancer Cells for Immune Targeting.
AB  - Altered cell metabolism is ubiquitous in cancer cells; however, it remains
      challenging to exploit these alterations for cancer therapy. A new study reveals
      that metabolic alterations to the urea cycle promote tumor growth but
      unexpectedly also trigger mutations that mark cancer cells for recognition by
      immunotherapy.

PMID- 30193110
TI  - Decoding the Genomics of Abdominal Aortic Aneurysm.
AB  - A key aspect of genomic medicine is to make individualized clinical decisions
      from personal genomes. We developed a machine-learning framework to integrate
      personal genomes and electronic health record (EHR) data and used this framework
      to study abdominal aortic aneurysm (AAA), a prevalent irreversible cardiovascular
      disease with unclear etiology. Performing whole-genome sequencing on AAA patients
      and controls, we demonstrated its predictive precision solely from personal
      genomes. By modeling personal genomes with EHRs, this framework quantitatively
      assessed the effectiveness of adjusting personal lifestyles given personal genome
      baselines, demonstrating its utility as a personal health management tool. We
      showed that this new framework agnostically identified genetic components
      involved in AAA, which were subsequently validated in human aortic tissues and in
      murine models. Our study presents a new framework for disease genome analysis,
      which can be used for both health management and understanding the biological
      architecture of complex diseases. VIDEO ABSTRACT.

PMID- 30193109
TI  - The Multifaceted Role of Chromosomal Instability in Cancer and Its
      Microenvironment.
AB  - Chromosomal instability (CIN) is a hallmark of human cancer, and it is associated
      with poor prognosis, metastasis, and therapeutic resistance. CIN results from
      errors in chromosome segregation during mitosis, leading to structural and
      numerical chromosomal abnormalities. In addition to generating genomic
      heterogeneity that acts as a substrate for natural selection, CIN promotes
      inflammatory signaling by introducing double-stranded DNA into the cytosol,
      engaging the cGAS-STING anti-viral pathway. These multipronged effects
      distinguish CIN as a central driver of tumor evolution and as a genomic source
      for the crosstalk between the tumor and its microenvironment, in the course of
      immune editing and evasion.

PMID- 30193112
TI  - Personalized Gut Mucosal Colonization Resistance to Empiric Probiotics Is
      Associated with Unique Host and Microbiome Features.
AB  - Empiric probiotics are commonly consumed by healthy individuals as means of life
      quality improvement and disease prevention. However, evidence of probiotic gut
      mucosal colonization efficacy remains sparse and controversial. We
      metagenomically characterized the murine and human mucosal-associated
      gastrointestinal microbiome and found it to only partially correlate with stool
      microbiome. A sequential invasive multi-omics measurement at baseline and during
      consumption of an 11-strain probiotic combination or placebo demonstrated that
      probiotics remain viable upon gastrointestinal passage. In colonized, but not
      germ-free mice, probiotics encountered a marked mucosal colonization resistance.
      In contrast, humans featured person-, region- and strain-specific mucosal
      colonization patterns, hallmarked by predictive baseline host and microbiome
      features, but indistinguishable by probiotics presence in stool. Consequently,
      probiotics induced a transient, individualized impact on mucosal community
      structure and gut transcriptome. Collectively, empiric probiotics supplementation
      may be limited in universally and persistently impacting the gut mucosa, meriting
      development of new personalized probiotic approaches.

PMID- 30193111
TI  - A Structured Tumor-Immune Microenvironment in Triple Negative Breast Cancer
      Revealed by Multiplexed Ion Beam Imaging.
AB  - The immune system is critical in modulating cancer progression, but knowledge of
      immune composition, phenotype, and interactions with tumor is limited. We used
      multiplexed ion beam imaging by time-of-flight (MIBI-TOF) to simultaneously
      quantify in situ expression of 36 proteins covering identity, function, and
      immune regulation at sub-cellular resolution in 41 triple-negative breast cancer
      patients. Multi-step processing, including deep-learning-based segmentation,
      revealed variability in the composition of tumor-immune populations across
      individuals, reconciled by overall immune infiltration and enriched co-occurrence
      of immune subpopulations and checkpoint expression. Spatial enrichment analysis
      showed immune mixed and compartmentalized tumors, coinciding with expression of
      PD1, PD-L1, and IDO in a cell-type- and location-specific manner. Ordered immune
      structures along the tumor-immune border were associated with
      compartmentalization and linked to survival. These data demonstrate organization
      in the tumor-immune microenvironment that is structured in cellular composition,
      spatial arrangement, and regulatory-protein expression and provide a framework to
      apply multiplexed imaging to immune oncology.

PMID- 30193113
TI  - Post-Antibiotic Gut Mucosal Microbiome Reconstitution Is Impaired by Probiotics
      and Improved by Autologous FMT.
AB  - Probiotics are widely prescribed for prevention of antibiotics-associated
      dysbiosis and related adverse effects. However, probiotic impact on post
      antibiotic reconstitution of the gut mucosal host-microbiome niche remains
      elusive. We invasively examined the effects of multi-strain probiotics or
      autologous fecal microbiome transplantation (aFMT) on post-antibiotic
      reconstitution of the murine and human mucosal microbiome niche. Contrary to
      homeostasis, antibiotic perturbation enhanced probiotics colonization in the
      human mucosa but only mildly improved colonization in mice. Compared to
      spontaneous post-antibiotic recovery, probiotics induced a markedly delayed and
      persistently incomplete indigenous stool/mucosal microbiome reconstitution and
      host transcriptome recovery toward homeostatic configuration, while aFMT induced
      a rapid and near-complete recovery within days of administration. In vitro,
      Lactobacillus-secreted soluble factors contributed to probiotics-induced
      microbiome inhibition. Collectively, potential post-antibiotic probiotic benefits
      may be offset by a compromised gut mucosal recovery, highlighting a need of
      developing aFMT or personalized probiotic approaches achieving mucosal protection
      without compromising microbiome recolonization in the antibiotics-perturbed host.

PMID- 30193116
TI  - SnapShot: Gut Immune Niches.
AB  - The intestinal milieu changes along the proximal to distal axis and across its
      tissue wall, according to the luminal content and tissue function.
      Correspondingly, highly specialized immune compartments can be found in each
      intestinal niche. To view this SnapShot, open or download the PDF.

PMID- 30193115
TI  - Reactivation of Dormant Relay Pathways in Injured Spinal Cord by KCC2
      Manipulations.

PMID- 30193114
TI  - Atlas of Circadian Metabolism Reveals System-wide Coordination and Communication
      between Clocks.
AB  - Metabolic diseases are often characterized by circadian misalignment in different
      tissues, yet how altered coordination and communication among tissue clocks
      relate to specific pathogenic mechanisms remains largely unknown. Applying an
      integrated systems biology approach, we performed 24-hr metabolomics profiling of
      eight mouse tissues simultaneously. We present a temporal and spatial atlas of
      circadian metabolism in the context of systemic energy balance and under chronic
      nutrient stress (high-fat diet [HFD]). Comparative analysis reveals how the
      repertoires of tissue metabolism are linked and gated to specific temporal
      windows and how this highly specialized communication and coherence among tissue
      clocks is rewired by nutrient challenge. Overall, we illustrate how dynamic
      metabolic relationships can be reconstructed across time and space and how
      integration of circadian metabolomics data from multiple tissues can improve our
      understanding of health and disease.

PMID- 30193117
TI  - Interdisciplinary Management of a Class III Anterior Open Bite Malocclusion in a
      Patient With Cerebral Palsy.
AB  - Dentofacial disharmony in patients with cerebral palsy (CP) can lead to low self
      esteem and functional limitations. However, medical and behavioral challenges in
      patients with developmental disorders often prevent dental practitioners from
      offering the necessary treatment. This report describes the clinical
      interdisciplinary management of a 20-year-old man with CP, including orthodontic,
      periodontal, and orthognathic surgery therapy. The patient presented with the
      chief complaint of having difficulty chewing, was wheelchair dependent, had poor
      orofacial muscle control, and exhibited a Class III malocclusion with a skeletal
      anterior open bite. The lower midline was shifted 3 mm to the right, there was
      severe maxillary spacing, and the patient had gingival overgrowth. A combined
      orthodontic, periodontal, and orthognathic surgery treatment approach was chosen
      to meet the patient's interdisciplinary needs. Because of his physical
      limitations, it was necessary to avoid complicated and prolonged orthodontic
      treatment mechanics. Interdisciplinary therapy improved the patient's oral
      function, periodontal health, and facial esthetics and led to a good occlusion,
      which remained stable 1 year after treatment. Regardless of the treatment
      challenges, combined orthodontic and surgical therapy in the present patient with
      CP led to favorable treatment results and improved the patient's self-esteem,
      confidence in social interactions, and speaking and chewing abilities.

PMID- 30193118
TI  - Does Viewing a Third Molar Informed Consent Video Decrease Patients' Anxiety?
AB  - PURPOSE: Before having impacted third molars removed, patients are frequently
      asked to view a brief video describing the operation and its benefits and risks.
      The purpose of this study was to determine whether such information reduces or
      increases patients' anxiety level. PATIENTS AND METHODS: In this prospective
      cohort study, 100 patients presenting for consultation regarding removal of their
      impacted third molars completed a form asking them to grade their anxiety level
      before and after viewing the informational video as calm, slightly anxious,
      moderately anxious, or very anxious. RESULTS: Thirty-one percent reported
      increased anxiety after viewing the video. Only 12% showed a decrease, and in
      57%, there was no change (28% were still slightly, moderately, or very anxious).
      Scoring of the pre- and post-viewing anxiety levels showed a statistically
      significant increase in anxiety after viewing. CONCLUSIONS: Viewing the video
      increased or did not reduce the anxiety level in a significant number of
      patients. Therefore, it is important to complement this video with positive
      verbal and written reinforcement of such aspects as patient comfort, procedural
      safety, and adequate pain control.

PMID- 30193119
TI  - Mandibular Advancement Means Lower Facial Enlargement: A 2-Dimensional and 3
      Dimensional Analysis.
AB  - PURPOSE: Bilateral sagittal split osteotomy (BSSO) is frequently used to treat
      Class II malocclusion for functional and esthetic purposes, with expected changes
      in the profile. The goal of this study was to assess transversal changes in
      mandibular advancement by comparing 3-dimensional (3D) photogrammetric
      modifications and 2-dimensional (2D) radiographic enlargement. MATERIALS AND
      METHODS: A cohort study was conducted of patients who underwent an isolated
      advancement BSSO (Obwegeser-Dal Pont II type) for a Class II malocclusion. All
      patients had 3D photogrammetric and 2D radiographic evaluations before and after
      surgery. Frontal cephalograms were used to measure the evolution of bigonial
      distance (BGD) and 3D photographs were used to measure the evolution of cutaneous
      BGD (CBGD). RESULTS: Fourteen patients were included. Mean mandibular advancement
      was 6 mm. BGD (+6.1 mm; P < 10-3) and CBGD (+4.2 mm; P = .0017) were
      significantly increased. The mean ratio of soft tissue response to transversal
      skeletal changes was 0.81. CONCLUSION: This 2D and 3D analysis of transversal
      modifications shows that advancement with the BSSO is responsible for marked
      lower third facial enlargement. This parameter must be taken into account during
      the preoperative esthetic assessment to ensure the provision of pertinent
      information to the patient and the consideration of complementary surgical
      correction.

PMID- 30193120
TI  - Implicit updating of object representation via temporal associations.
AB  - The cognitive system can flexibly update the representations of objects upon
      changes in the physical properties of the objects. Can the changes ripple to the
      representations of other associated objects that are not directly observable? We
      propose that statistical learning allows changes in one object to be
      automatically transferred to related objects. Observers viewed a temporal
      sequence with pairs of colored circles where the first circle always preceded the
      second. When the first circle increased or decreased in size, the second circle
      was judged to be larger (or smaller), suggesting that changes were automatically
      transferred to the second object (Experiment 1). When the second circle changed
      in size, the first circle was unaffected (Experiment 2). The strength of transfer
      seemed to depend on the conditional probability between objects (Experiment 3).
      The findings were replicated using pairs of faces that changed in expressions
      (Experiments 4&5). Importantly, no observer was explicitly aware of the pairs.
      Thus, statistical learning enables automatic and implicit updating of object
      representations upon changes to temporally associated objects.

PMID- 30193121
TI  - Influence of different lignan compounds on enterolignan production by
      Bifidobacterium and Lactobacillus strains.
AB  - Enterolignans, i.e. enterodiol and enterolactone, are polyphenols derived from
      the microbial metabolism of dietary lignans. They are considered phytoestrogens
      because of their estrogenic/antiestrogenic activity, which confers them benefits
      to human health when they reach sufficient levels in plasma. Hence, there is a
      great interest in studying the bacteria involved in enterolignan production. In
      the present study, three bifidobacterial strains (Bifidobacterium bifidum INIA
      P466, Bifidobacterium catenulatum INIA P732 and Bifidobacterium pseudolongum INIA
      P2) were found capable of producing low levels of enterodiol (2-11 MUM) from
      lignan extracts; while another one (Bifidobacterium pseudocatenulatum INIA P946)
      was found to produce an important increment of the lignan secoisolariciresinol
      (SECO). Subsequently, the three enterodiol-producing bifidobacteria and another
      three Lactobacillus strains previously identified as enterolignans producers
      (Lactobacillus gasseri INIA P508, Lactobacillus salivarius INIA P448 and Lb.
      salivarius INIA P183), were tested on pure lignans yielding both enterodiol and
      enterolactone from secoisolariciresinol (SECO), while they did not metabolised
      the other lignan tested (i.e. matairesinol). B. catenulatum INIA P732 and Lb.
      gasseri INIA P508 were the strains that transformed the greatest percentage of
      SECO, yielding enterolactone concentrations above 2 mM. In addition, the
      formation of the intermediate compound dihydroxyenterodiol was observed as part
      of SECO transformation by all the strains. In this work, we have demonstrated for
      the first time how strains of Bifidobacterium and Lactobacillus are capable of
      carrying out the complete enterolignan metabolism, transforming a purified lignan
      (SECO) into enterodiol and enterolactone. The isolation and characterization of
      bacteria able to metabolize lignans and produce enterolignans, especially
      belonging to Bifidobacterium and Lactobacillus genera, is of biotechnological
      interest, because of their potential application in functional foods and as
      probiotics.

PMID- 30193122
TI  - Inhibition of Fusarium trichothecene biosynthesis by yeast extract components
      extractable with ethyl acetate.
AB  - While Fusarium graminearum readily produces trichothecenes in complex media
      containing sucrose as the carbon source (YS_60), the amount of the mycotoxin is
      quite limited when other sugars, such as glucose and fructose, are used. We found
      that autoclaving of media containing fructose and yeast extract (YF_60) results
      in the formation of inhibitors of trichothecene biosynthesis by F. graminearum
      JCM 9873, a strain that produces 15-acetyldeoxynivalenol (15-ADON) in liquid
      culture. Removal of the solvent fraction from the autoclaved media after ethyl
      acetate extraction attenuated the inhibitory activity against trichothecene
      production. In addition, extraction of the non-autoclaved complex media with
      ethyl acetate, followed by removal of the solvent fraction, similarly resulted in
      increased accumulation of the mycotoxin. Although the increase in trichothecene
      production differed considerably among fungal strains and yeast extract products,
      F. graminearum species complex generally responded to the medium treatments in
      the same way. These results suggest that some hydrophobic substances that arise
      during the drying and heating of yeast extract negatively affected trichothecene
      production in liquid culture. Modes of actions of inhibitory substances were
      partially characterized using strain JCM 9873, with focus on the transcriptional
      and functional analyses of Tri6, a key regulator gene in trichothecene
      biosynthesis. The presence of the ethyl acetate-extractable substances in
      autoclaved YF_60 media decreased the relative transcription level of Tri6, as
      well as that of a trichodiene synthase gene Tri5. Thus, the substances exerted
      their inhibitory action through suppression of Tri6 expression. By using a yeast
      extract lot that completely prevented trichothecene production by the wild-type
      strain in autoclaved YS_60 medium, we prepared YF_60 media and cultured a
      constitutive Tri6 overexpressor strain described by Maeda et al. (2018). Despite
      the high transcription level of Tri6, the presence of the ethyl acetate
      extractable-substances suppressed 15-ADON production. These results suggested
      that both Tri6p-independent initial activation of Tri6 expression and subsequent
      Tri6p-dependent activation of Tri expression were affected by the hydrophobic
      substances in the yeast extract products.

PMID- 30193123
TI  - Detection of Listeria spp. and L. monocytogenes in pooled test portion samples of
      processed dairy products.
AB  - Listeria monocytogenes is a major foodborne pathogen. Testing multiple portions
      of the same final product is often required to verify the effectiveness of a food
      safety management system. Therefore, it will be advantageous to the laboratories
      to combine these test portions and process as one sample. However, combining
      samples for analysis, i.e., pooling, can be done only if there is no negative
      impact on the result. The objective of this study was to validate pooling of test
      portions for the detection of L. monocytogenes and Listeria spp. in dairy
      products as no scientific evidence currently exists to support this practice. Six
      representative matrices, namely, pudding, yogurt, brie cheese, 2% milk, ice cream
      and infant formula were spiked separately with stressed L. monocytogenes and
      Listeria spp. in 25 g and pooled test portions (375 g/250 g/125 g). Two methods,
      namely, ISO-11290-1:1996 Amd1:2004 and a validated alternative method
      Rapid'L.Mono were used for sample testing. Performance of a method in pooled test
      portions was considered to be satisfactory if the relative limit of detection
      (RLOD50; LOD50 [pooled test portion]/LOD50 [25 g test portion]) and limit of
      detection (LOD50) obtained was <=2.5 and 1 CFU or MPN, respectively. Results
      obtained from L. monocytogenes and Listeria spp. trials were given equal
      weightage to decide on the impact of pooling. Acceptable RLOD50 and LOD50 values
      were consistently obtained in L. monocytogenes and Listeria spp. inoculation
      experiments when test portions were pooled up to 125 g for all matrices tested
      with both methods. While there was a slight delay for the primary enrichment of
      the pooled test portions to reach the desired incubation temperature when
      compared to the 25 g test portions, it did not negatively impact the outcome when
      samples were pooled up to 125 g. Background organisms were in general present at
      low concentrations and did not seem to adversely impact the recovery of the
      target organism in 125 g samples. Thus, pooling of test portions to up to 125 g
      for the detection of L. monocytogenes and Listeria spp. by two culture methods in
      processed dairy products has been validated.

PMID- 30193124
TI  - Antifungal activity of proteolytic fraction (P1G10) from (Vasconcellea
      cundinamarcensis) latex inhibit cell growth and cell wall integrity in Botrytis
      cinerea.
AB  - The aim of this study was to determine the antifungal activity of the proteolytic
      fraction P1G10 from Vasconcellea cundinamarcencis (ex-Carica candamarcensis)
      against Botrytis cinerea, the causative agent of pre- and postharvest damaging
      disease in fruit and vegetables. The survival of B. cinerea at different
      concentrations of P1G10 showed that 1 mg/mL inhibited 50% of mycelium growth
      after 72 h incubation. The kinetic of growth inhibition fits the Weibull
      distribution function, and the data was confirmed by the IC50 survival assay. The
      study shows that P1G10 inhibits conidia germination and germ tube elongation of
      B. cinerea relative to untreated conidia. Hypersensitivity to cell wall
      perturbing agents (Calcofluor white and Congo red) was observed in mycelium cells
      treated with P1G10. In addition, P1G10 exhibited inhibitory effect on the
      adhesion of conidia, provoked alterations in membrane integrity and induced
      production of reactive oxygen species accompanied by cellular damage. Our results
      highlight the effect of P1G10 on mycelium growth, cell wall alterations, membrane
      integrity and adhesion. P1G10 emerges as promising antifungal to control disease
      causing agents in the food agroindustry.

PMID- 30193126
TI  - An Unexpected Calm: Mfge8 Controls Stem Cell Quiescence and Maintenance.
AB  - Radial glia-like neural stem cells (RGLs) in the mouse hippocampus generate
      neurons throughout life, but RGL maintenance mechanisms remain unclear. In this
      issue of Cell Stem Cell, Zhou et al. (2018) identified Mfge8, a well-known
      mediator of the "eat-me" signal, as a factor that reinforces quiescence and
      protects the RGL niche from depletion.

PMID- 30193128
TI  - Revert the SIRT: Normalizing SIRT1 Activity in Myelodysplastic Stem Cells.
AB  - Myelodysplastic syndromes are hematologic malignancies with few treatment options
      and a propensity to transform to acute myeloid leukemia. In this issue of Cell
      Stem Cell, Sun et al. (2018) report that low SIRT1 levels in myelodysplastic stem
      cells contribute to aberrant self-renewal through enabling hyperacetylation and
      reduced activity of TET2.

PMID- 30193127
TI  - Obliterating Obstacles to an Odyssey.
AB  - Why is reprogramming to generate induced pluripotent stem cells (iPSCs) a
      protracted and inefficient odyssey? In this issue of Cell Stem Cell, Mor et al.
      (2018) hypothesize that reprogramming factors paradoxically activate and inhibit
      pluripotency gene expression and show that eliminating Gatad2a (a NuRD
      corepressor complex subcomponent) rapidly and efficiently reprograms multiple
      cell types into iPSCs.

PMID- 30193129
TI  - Studying Tumor-ReacTive T Cells: A Personalized Organoid Model.
AB  - Recently in Cell, Dijkstra et al. (2018) introduced a tumor organoid/lymphocyte
      co-culture-based approach to expand and analyze tumor-specific T cell responses
      in a patient-specific manner. The platform is applicable for epithelial cancers
      and may have significant value for clinical translation of novel personalized
      immunotherapies.

PMID- 30193125
TI  - Prolonged furosemide exposure and risk of abnormal newborn hearing screen in
      premature infants.
AB  - BACKGROUND: At very high doses, furosemide is linked to ototoxicity in adults,
      but little is known about the risk of hearing loss in premature infants exposed
      to furosemide. AIMS: Evaluate the association between prolonged furosemide
      exposure and abnormal hearing screening in premature infants. STUDY DESIGN: Using
      propensity scoring, infants with prolonged (>=28 days) exposure to furosemide
      were matched to infants never exposed. The matched sample was used to estimate
      the impact of prolonged furosemide exposure on the probability of an abnormal
      hearing screen prior to hospital discharge. SUBJECTS: A cohort of infants 501
      1250 g birth weight and 23-29 weeks gestational age discharged home from 210
      neonatal intensive care units in the United States (2004-2013). OUTCOME MEASURES:
      We defined abnormal hearing screen as a result of either "fail" or "refer" for
      either ear. RESULTS: Altogether, 1020 infants exposed to furosemide for >=28 days
      were matched to 790 unique infants never exposed, yielding a total of 1042
      matches due to sampling with replacement and propensity score ties. Matching
      resulted in a population similar in baseline characteristics. After adjusting for
      covariates, the proportion of infants with an abnormal hearing screen in the
      furosemide-exposed group was not significantly higher than the never-exposed
      group (absolute difference 3.0% [95% CI -0.2-6.2%], P = 0.07). CONCLUSIONS:
      Prolonged furosemide exposure was associated with a positive, but not
      statistically significant, difference in abnormal hearing screening in premature
      infants. Additional studies with post-hospital discharge audiology follow-up are
      needed to further evaluate the safety of furosemide in this population.

PMID- 30193130
TI  - Future AAVenues for In Utero Gene Therapy.
AB  - Fetal gene therapy using safe and effective viral vectors no longer remains a
      distant prospect. Recently in Nature Medicine, Massaro et al. (2018) demonstrated
      that prenatal intracranial injection of a viral vector results in improved
      neurologic function, raising the intriguing possibility that in utero gene
      therapy may be approaching clinical applications.

PMID- 30193131
TI  - Moving iPSC-Derived Cardiomyocytes Forward to Treat Myocardial Infarction.
AB  - Human pluripotent stem cell-derived cardiomyocytes represent a promising cell
      source for cardiac repair. However, their clinical translation is hindered by
      limited evidence for functional benefits in primate models, potential risks for
      arrhythmias, and teratoma formation. A recent study by Liu et al. (2018) makes
      significant progress on these critical issues.

PMID- 30193132
TI  - Regenerating Eye Tissues to Preserve and Restore Vision.

PMID- 30193133
TI  - Competence for basic midwifery practice: Updating the ICM essential competencies.
AB  - OBJECTIVE: To obtain consensus amongst midwifery experts globally about the
      essential competencies for basic midwifery practice. DESIGN: A modified Delphi
      approach, involving a three-round online survey. PARTICIPANTS: Midwifery leaders,
      educators and regulators in all ICM regions, along with representatives of
      organisations affiliated to ICM. METHODS: The research team worked closely with a
      Core Working Group and a Task Force. An initial set of competencies and
      components was developed through a content analysis of existing competency
      documents and presented to participants in Round 1 of the survey. Items
      identified as essential by at least 85% of participants were endorsed. Remaining
      items and new items identified by participants were returned to participants in
      Rounds 2 and 3 for further rating. FINDINGS: The study achieved a wide sample
      representative of midwifery experts across all ICM regions and countries,
      language groups, and income categories. Only a small number of competencies
      relating to the wider role of the midwife were endorsed as essential
      competencies. Competencies and components relating to professional and personal
      attributes were extended. Although most competencies and components relating to
      core midwifery practice were endorsed as essential competencies, several were
      rejected relating to abortion-related care, cancer screening, infertility, and
      gynaecology. Findings are, nevertheless, highly consistent with the scope of
      practice delineated in the current 2010/2013 version of the ICM Essential
      Competencies for Basic Midwifery Practice. KEY CONCLUSIONS AND IMPLICATIONS FOR
      PRACTICE: The extension of professional and personal attributes reflects the
      recent emphasis on respectful midwifery care. The rejection of most of the
      additional competencies and components relating to the wider role of the midwife
      and endorsement of most of those considered to relate to core midwifery practice
      indicates that the scope of midwifery practice remains essentially unchanged
      through 2017.

PMID- 30193134
TI  - Full reversal of an atypical right pericallosal artery infarction assessed by
      multimodal magnetic resonance imaging.

PMID- 30193135
TI  - Lenalidomide induced reversible parkinsonism, dystonia, and dementia in
      subclinical Creutzfeldt-Jakob disease.

PMID- 30193137
TI  - Mutations in TOP3A Cause a Bloom Syndrome-like Disorder.

PMID- 30193136
TI  - The Clinical Sequencing Evidence-Generating Research Consortium: Integrating
      Genomic Sequencing in Diverse and Medically Underserved Populations.
AB  - The Clinical Sequencing Evidence-Generating Research (CSER) consortium, now in
      its second funding cycle, is investigating the effectiveness of integrating
      genomic (exome or genome) sequencing into the clinical care of diverse and
      medically underserved individuals in a variety of healthcare settings and disease
      states. The consortium comprises a coordinating center, six funded extramural
      clinical projects, and an ongoing National Human Genome Research Institute
      (NHGRI) intramural project. Collectively, these projects aim to enroll and
      sequence over 6,100 participants in four years. At least 60% of participants will
      be of non-European ancestry or from underserved settings, with the goal of
      diversifying the populations that are providing an evidence base for genomic
      medicine. Five of the six clinical projects are enrolling pediatric patients with
      various phenotypes. One of these five projects is also enrolling couples whose
      fetus has a structural anomaly, and the sixth project is enrolling adults at risk
      for hereditary cancer. The ongoing NHGRI intramural project has enrolled
      primarily healthy adults. Goals of the consortium include assessing the clinical
      utility of genomic sequencing, exploring medical follow up and cascade testing of
      relatives, and evaluating patient-provider-laboratory level interactions that
      influence the use of this technology. The findings from the CSER consortium will
      offer patients, healthcare systems, and policymakers a clearer understanding of
      the opportunities and challenges of providing genomic medicine in diverse
      populations and settings, and contribute evidence toward developing best
      practices for the delivery of clinically useful and cost-effective genomic
      sequencing in diverse healthcare settings.

PMID- 30193140
TI  - Schizophrenia in type 2 diabetes mellitus: Prevalence and clinical
      characteristics.
AB  - BACKGROUND: This study investigated the prevalence and characteristics of
      schizophrenia in patients with type 2 diabetes mellitus (T2DM) in Taiwan.
      METHODS: National Health Insurance claims data for patients with principal
      diagnoses of schizophrenia and T2DM were analysed. RESULTS: Compared with
      patients with schizophrenia in the general population (GP), those with
      schizophrenia and T2DM were more likely to have higher Charlson comorbidity index
      (CCI) scores and multiple comorbidities, and were older. The prevalence of
      schizophrenia was significantly higher in patients with T2DM than in the GP from
      2000 to 2010. In addition, during this period, the prevalence of schizophrenia in
      patients with T2DM increased from 0.64% to 0.85%; such an increase in the GP was
      also observed. A high prevalence of schizophrenia was observed in patients with
      T2DM aged less than 60 years old; those residing in eastern Taiwan; those with
      incomes of <=NT$17,280, NT$17,281-NT$22,880, NT$22,881-NT$28,800, and NT$36,301
      NT$45,800; and those with CCI > 2. CONCLUSIONS: Our study found the prevalence of
      schizophrenia is higher in patients with T2DM than in the GP, particularly those
      with earlier ages less than 60 years old. Public health initiatives are necessary
      to prevent and treat schizophrenia in patients with T2DM, specifically for those
      with the aforementioned and premature death risk.

PMID- 30193141
TI  - Other Specified Feeding or Eating Disorders (OSFED): Clinical heterogeneity and
      cognitive-behavioral therapy outcome.
AB  - BACKGROUND: with the DSM-5 new eating disorders (EDs) diagnostic subtypes were
      identified within the Other Specified Feeding or Eating Disorders (OSFED)
      category, which have so far been under-researched. Objectives of this study were
      to examine differential features among OSFED subtypes, exploring short-term
      cognitive-behavioral therapy (CBT) response and identifying clinical predictors
      of therapy outcome. METHODS: the sample included 176 female patients diagnosed
      with OSFED [82 atypical anorexia nervosa (atypical-AN), 57 purging disorder (PD),
      and 37 subthreshold bulimia nervosa (sub-BN)]. Assessment included eating
      related, psychopathological and personality measures. RESULTS: results showed
      similar clinical and personality profiles between the diagnostic subtypes, with
      hardly any differences, only observable in the core symptoms of each diagnosis.
      The sub-BN group was the one which showed more social impairment. Regarding
      treatment outcome, the three groups did not reveal significant differences in
      remission rates, therapeutic adherence or dropout rates, reaching rates of
      dropout from 36.8% to 50% (p = .391). However, different ED subtype predictors
      appear related with full remission or dropout risk, specifically personality
      traits. CONCLUSIONS: our results suggest that OSFED patients may benefit
      similarly from the same CBT outpatient group approach. However, high dropout
      rates and low motivation seems to be an important limitation and challenge for
      future approaches.

PMID- 30193139
TI  - Retraction Notice to: Nested Inversion Polymorphisms Predispose Chromosome
      22q11.2 to Meiotic Rearrangements.

PMID- 30193142
TI  - Severe hair loss associated with psychotropic drugs in psychiatric inpatients
      Data from an observational pharmacovigilance program in German-speaking
      countries.
AB  - BACKGROUND: The study aimed to investigate severe hair loss related to
      psychotropic drugs (PDs) by using data from the drug safety programme
      Arzneimittelsicherheit in der Psychiatrie (AMSP). METHODS: Data on PD utilization
      and reports of severe PD-related hair loss were collected in 83 psychiatric
      hospitals in Austria, Germany and Switzerland during the period 1993-2013.
      RESULTS: Out of 432,215 patients under surveillance, 404,009 patients were
      treated with PDs for the main indications of depression, schizophrenic disorder,
      neurosis, mania, and organic psychosis. Severe hair loss related to PD treatment
      was reported in 43 cases (0.01%). The rates of hair loss under antipsychotic
      drugs were slightly lower than the mean rates of all PDs and antidepressant
      drugs. Valproic acid was related to the highest risk. In 6 of the 43 cases, hair
      loss was imputed to multiple drugs, with 4 cases imputed to double drug
      combinations and 2 cases to triple combinations. Rates of severe hair loss under
      valproic acid (VPA) and lithium salts were distinctly lower as compared with the
      overall rates reported in literature. Severe hair loss under PD treatment was
      reported significantly more often in female patients than in male patients (p <
      0.01). CONCLUSION: The rate of severe PD-related hair loss was very low in the
      present survey. The large number of patients included in this multicentre study
      allows for assessment and comparison of hair loss rates related to different PDs
      and groups of PDs and provides new and supplementary information on PD-related
      hair loss.

PMID- 30193143
TI  - Xylarianins A-D from the endophytic fungus Xylaria sp. SYPF 8246 as natural
      inhibitors of human carboxylesterase 2.
AB  - Eighteen secondary metabolites were isolated from the fermentation broth of the
      endophytic fungus Xylaria sp. SYPF 8246, including four new compounds,
      xylarianins A-D (1-4), three new natural products, 6-methoxycarbonyl-2'-methyl
      3,5,4',6'-tetramethoxy-diphenyl ether (5), 2-chlor-6-methoxycarbonyl-2'-rnethyl
      3,5,4',6'-tetramethoxy-diphenyl ether (6), and 2-chlor-4'-hydroxy-6-methoxy
      carbonyl-2'-methyl-3,5,6'-trimethoxy-diphenyl ether (7), and eleven known
      compounds (8-18). Their structural elucidations were conducted by using 1D and 2D
      NMR, HRESIMS, and Rh2(OCOCF3)4-induced electronic circular dichroism (ECD)
      spectra analyses. The integrated 1H and 13C NMR data of three new natural
      products 5-7 were reported for the first time. All the isolated compounds were
      assayed for their inhibitory activities against human carboxylesterase 2 (hCE 2).
      Compounds 1, 5-9, and 18 displayed significant inhibitory activities against hCE
      2 with IC50 values of 10.43 +/- 0.51, 6.69 +/- 0.85, 12.36 +/- 1.27, 18.25 +/-
      1.78, 29.78 +/- 0.48, 18.86 +/- 1.87, and 20.72 +/- 1.51 uM, respectively. The
      interactions between compounds 1 and 5 with hCE 2 were anaylzed by molecular
      docking.

PMID- 30193144
TI  - Interface self-assembly preparation of multi-element doped carbon nanobowls with
      high electrocatalysis activity for oxygen reduction reaction.
AB  - Developing an efficient, stable and low cost oxygen reduction reaction
      electrocatalyst is desirable for fuel cells and metal-air batteries. Here, we
      have successfully prepared multi-element doped carbon nanobowls by simply mixing
      the porous carbon nanobowls and sulfur doped graphitic carbon nitride quantum
      dots in FeCl3 solution and subsequent high temperature treatment processes.
      Compared with the commercial Pt/C electrocatalyst, the multi-element doped carbon
      nanobowls display a comparable half-wave potential of 0.82 V, much larger
      limiting diffusion current density (0.4-0.8 V), better methanol-tolerance and
      higher long-term stability for the oxygen reduction reaction in alkaline media.
      The robust three-dimensional porous structure of carbon nanobowls and multiple
      active centers derived from Fe, N, S and O co-doping are responsible for the
      excellent performance. This work suggests that such multi-element doped carbon
      nanobowls can be a promising alternative for Pt-based catalysts in fuel cells.

PMID- 30193145
TI  - Synthesis of ultra-large ZrO2 nanosheets as novel adsorbents for fast and
      efficient removal of As(III) from aqueous solutions.
AB  - Consumption of water having excessive arsenic (As) contamination can cause
      adverse health effects on human beings. In this study, novel ultra-large
      zirconium oxide (ZrO2) nanosheets were successfully synthesized using graphene
      oxide (GO) templates and their adsorption-ability was studied for arsenite
      (As(III)). Owing to higher values of surface area, numbers of available hydroxyl
      groups and strong chemisorption binding affinity towards As(III), the synthesized
      novel ultra-large ZrO2 nanosheets showed high adsorption-ability for As(III) over
      a wide pH range. Experimental results demonstrated that the maximum adsorption
      ability of the ZrO2 nanosheets for As(III) reached to 74.9 mg/g at pH 6. BET,
      zeta potential, effect of initial pH, FTIR and XPS have been used to analyze the
      As(III) adsorption process on the ZrO2 nanosheets. The experiments for effects of
      co-existing ions indicated that ZrO2 nanosheets possessed good anti-interference
      ability towards co-existing ions. Furthermore, the ZrO2 nanosheets demonstrated
      very fast and excellent treatment of simulated real As(III) polluted water,
      consequently the effluent concentration met the standard regulated by World
      Health Organization. This study suggested that the as-prepared ZrO2 nanosheets
      could be potentially applied in practical drinking water treatment.

PMID- 30193146
TI  - Aggregation of Ag(0) nanoparticles to unexpected stable chain-like assemblies
      mediated by 2,2'-bipyridine decorated peptoids.
AB  - We report a unique example of Ag(0) nanoparticles (NPs)-assemblies stabilized by
      2,2-bipyridine (BP), via the incorporation of BP at the N-terminus of a peptoid
      heptamer bearing phenylethyl groups in the other positions. We show that this
      peptoid mediates the aggregation of the Ag(0) NPs into nanochain-like assemblies.
      Transmission electron microscopy, supported by UV-Vis spectroscopy analysis,
      revealed pre-assembly of the BP-peptoid oligomers into elongated pearl-like
      morphology, which serve as a template for the NPs. The fact that completely
      synthetic biomimetic oligomers can template and control the assembly of metal
      NPs, and specifically Ag(0), represents a conceptual mimic of the interaction
      between biomolecules and minerals for the production of nanostructured inorganic
      materials with complex morphologies.

PMID- 30193138
TI  - IRF2BPL Is Associated with Neurological Phenotypes.

PMID- 30193147
TI  - Tailored synthesis of polymer-brush-grafted mesoporous silicas with N-halamine
      and quaternary ammonium groups for antimicrobial applications.
AB  - Antimicrobial mesoporous materials with polymer brushes on the surface were
      prepared, and their structure and antimicrobial performance investigated. Poly
      ((3-acrylamidopropyl) trimethylammonium chloride) (PAPTMAC) modified mesoporous
      silica was prepared by a polymer-brush-grafted method through treatment with the
      initiator 4,4'-azobis (4-cyanovaleric acid) (ACVA) and polymerized with (3
      acrylamidopropyl) trimethylammonium chloride (APTMAC). A covalent bond was formed
      between mesoporous silica and N-halamine precursor; N-H bonds were successfully
      transformed to N-Cl bonds after chlorination. Morphology and structure of
      mesoporous silica were affected to some extent after modification. The surface
      area of the polymerized sample decreased, but was sufficient for further
      applications. Compare to the original sample, antimicrobial properties of the
      polymerized samples with quaternary ammonium groups (QAS) increased slightly.
      After exposure to dilute household bleach, the chlorinated samples showed
      excellent antimicrobial properties against 100% of S. aureus (ATCC 6538) (7.63
      log) and E. coli O157:H7 (ATCC 43895) (7.52 log) within 10 min. The prepared
      mesoporous silicas with effective antimicrobial properties could be very useful
      for potential application in water filtration.

PMID- 30193148
TI  - Oxygen vacancies modulated Bi-rich bismuth oxyiodide microspheres with tunable
      valence band position to boost the photocatalytic activity.
AB  - How to optimize the photogenerated electron-hole pairs' separation efficiency and
      redox performance of defective photocatalysts is still a concern for
      photocatalysis research. In this study, rich oxygen vacancy was introduced in
      Bi7O9I3 microsphere (Bi7O9I3-OVR) via a facile ionic liquid assisted solvothemal
      method to investigate the charge separation and photocatalytic performance. To
      demonstrate the dominant role of the introduced oxygen vacancy, partial oxygen
      vacancy in Bi7O9I3 microsphere was repaired by post-calcination treatment
      (Bi7O9I3-OVL), which was confirmed by electron paramagnetic resonance (EPR). The
      experimental results indicated the introduction of oxygen vacancy boosted the
      holes mobility and electrons reduction of Bi7O9I3, then the increased charge
      carriers' separation efficiency and high concentration of produced reactive
      oxygen species was realized. Benefiting from these, the Bi7O9I3-OVR microsphere
      exhibited a better photocatalytic oxygen evolution performance than Bi7O9I3-OVL,
      and the oxygen evolution rate was up to 2.66 MUmol m-2 h-1.

PMID- 30193149
TI  - A surface enhanced Raman scattering based colloid nanosensor for developing
      therapeutic drug monitoring.
AB  - Competitive reactions, on the surface of plasmonic nanostructures, allow
      exploiting SERS signals for quantitative Therapeutic Drug Monitoring. As an
      example, the concentration of Erlotinib, an anti-EGFR small molecule, used for
      the treatment of non-small cell lung and pancreatic cancer, is determined. The
      numerous side effects and the variability of patient responses make Erlotinib a
      good candidate for monitoring. The new SERS based sensor can estimate Erlotinib
      down to nanomolar concentration and is based on the chemical reaction of the drug
      and of a competitor SERS reporter on the surface of gold nanostructures. Colloid
      solutions of naked gold nanoparticles obtained by laser ablation in solution were
      used for obtaining nanostructures with very efficient hot spots for SERS and with
      a clean surface for chemistry. Detection of the drug in the nanomolar
      concentration range is shown to be possible also in spiked plasma samples.

PMID- 30193150
TI  - Recent advances in combinatorial drug screening and synergy scoring.
AB  - Treatment of complex diseases such as cancer, cardiovascular disease, diabetes or
      neurological disorders frequently warrants the utilization of drug combinations
      for therapeutic intervention. In fact, the most successful example is the current
      standard of care for HIV patients. However, identification of successful drug
      cocktails is not a simple task and is hampered by lack of standardization in
      terminology, experimental protocols and models as well as data analysis. Here we
      discuss the most recent developments in combinatorial drug screening by covering
      technological advancements in screening strategies, cellular model systems as
      well as novel drug classes. We believe the research progress being made provides
      promising basis to build on and identify, develop and optimize efficacious
      clinically relevant combinatorial drug treatments.

PMID- 30193151
TI  - Carcass concealment alters assemblages and reproduction of forensically important
      beetles.
AB  - Most forensic studies have examined decomposition and insect colonization for
      estimating the minimum postmortem interval (PMImin) using carcasses that are
      readily accessible to insects but in homicides, cadavers are often concealed to a
      certain extent. Here, we tested the hypothesis that the type of concealment of a
      decomposing resource and the permeability of the material used affect to
      different extents the animals attracted to the resource. To this end, beetle
      assemblages were documented for 100days on 15 domestic pig carcasses, placed
      individually in soft shell suitcases, trashcans with a hinged lid, and sealable
      drums in an untended open field in New Brunswick, Canada. Five pigs were
      allocated to each treatment. During the study, almost 33,000 beetle occurrences
      from 50 recognizable taxonomic units were documented around containers that
      concealed carcasses. Results indicated that trashcans, drums, and suitcases had
      different effects on the patterns of beetle arrival and departure from the
      vicinity of concealed carcasses, on beetle assembly, on their breeding
      strategies, as well as on the interspecific relationships between beetles of
      forensic importance. Of the 50 recognizable taxonomic units, only six species
      exhibited a somewhat predictable occurrence and yielded information about the
      time of placement or the type of container. Results also suggested that some of
      the abundant Silphidae species opted to breed or feed in suboptimal conditions or
      at a later period to avoid competing with the dominant silphid Necrodes
      surinamensis (Fabr.). This suggests the occurrence of preferential colonization
      and/or asymmetrical competition between beetle species, which would affect the
      potential of these species for PMImin estimations on concealed carcasses.

PMID- 30193152
TI  - Prevalence of bullying in a pediatric sample of body dysmorphic disorder.
AB  - Little is known about etiological factors in Body dysmorphic disorder (BDD).
      Cognitive behavioral and diathesis-stress models have implicated teasing and
      bullying as significant early environmental stressful triggers. Due to these
      implications, this study aimed to assess the emergence of BDD in children during
      early development, and to see if bullying experiences played a role in its
      development. A total of 219 children ages 7 to 10 were screened for
      psychopathology. Children were separated into four groups including a BDD group,
      an OCD group, a clinical control group (consisting of depressive disorders,
      attention deficit hyperactivity disorder, oppositional defiant disorder, and
      anxiety disorders not otherwise specified), and a non-clinical control group.
      Children were given questionnaires to evaluate their bullying and victimization
      experiences. It was hypothesized that children with BDD would experience more
      instances of victimization than children with OCD, clinical controls, and non
      clinical controls. Contrary to the hypothesis, results indicated that children
      with BDD symptoms were significantly more likely to be perpetrators of bullying
      than the other groups [F (3, 27.082) = 17.892, p < .001]. In addition to scoring
      high on the bullying questionnaires, children with BDD scored high on victim
      questionnaires as well, suggesting a link between these two peer interpersonal
      conflicts. The results of this study suggest that bullying behavior might be an
      unknown characteristic in young children with emerging BDD pathology.

PMID- 30193153
TI  - Family functioning in youth at-risk for serious mental illness.
AB  - BACKGROUND: There is evidence that family functioning can be impaired in families
      of individuals with schizophrenia, first-episode psychosis, bipolar disorder, and
      recurrent depression, which are considered to be serious mental illnesses (SMI).
      Poor family functioning is one of the predictors of the course of SMI. However,
      it is unclear if poor family functioning is a result of illness, or conversely if
      poor family leads to higher risk of illness. Nonetheless, family functioning may
      be impaired even before the onset of illness, and little is known about earlier
      stages of risk and the importance of the family environment for youth at-risk for
      SMI. OBJECTIVE: The present study aimed to examine differences in family
      functioning in a sample of youth at-risk of SMI across different clinical stages
      compared to healthy controls (HCs). METHODS: Family functioning was evaluated
      with the Family Adaptability and Cohesion Evaluation Scales-IV (FACES-IV) for 41
      non-help seeking youth with risk factors for SMI (Stage 0), 52 help-seeking youth
      with early mood and anxiety symptoms and distress (Stage 1a), 108 youth with an
      attenuated psychiatric syndrome (Stage 1b), and 42 HCs. RESULTS: Results from
      multivariate linear regression analyses showed that participants in Stage 1a and
      Stage 1b significantly differ from participants in Stage 0 and HCs on most of the
      family functioning scales. However, these results were statistically but not
      clinically significant as the percentile values for each group fell within the
      same clinical ranges. The only clinical difference was that participants in
      stages 1a and 1b were somewhat less satisfied with their family compared to
      healthy controls and stage 0 participants. CONCLUSIONS: An examination of group
      mean values demonstrated no difference in family functioning between the
      different groups with all groups in the healthy functioning range. However,
      family satisfaction is lower in youth at-risk for SMI who present with early
      signs of mood, anxiety or subthreshold psychotic symptoms than other
      participants. Early family psychoeducational interventions could be beneficial to
      improve family functioning.

PMID- 30193154
TI  - Mobile Universal Lexicon Evaluation System (MULES) in MS: Evaluation of a new
      visual test of rapid picture naming.
AB  - OBJECTIVE: The Mobile Universal Lexicon Evaluation System (MULES) is a test of
      rapid picture naming that is under investigation for concussion. MULES captures
      an extensive visual network, including pathways for eye movements, color
      perception, memory and object recognition. The purpose of this study was to
      introduce the MULES to visual assessment of patients with MS, and to examine
      associations with other tests of afferent and efferent visual function. METHODS:
      We administered the MULES in addition to binocular measures of low-contrast
      letter acuity (LCLA), high-contrast visual acuity (VA) and the King-Devick (K-D)
      test of rapid number naming in an MS cohort and in a group of disease-free
      controls. RESULTS: Among 24 patients with MS (median age 36 years, range 20-72,
      64% female) and 22 disease-free controls (median age 34 years, range 19-59, 57%
      female), MULES test times were greater (worse) among the patients (60.0 vs. 40.0
      s). Accounting for age, MS vs. control status was a predictor of MULES test times
      (P = .01, logistic regression). Faster testing times were noted among patients
      with MS who had greater (better) performance on binocular LCLA at 2.5% contrast
      (P < .001, linear regression, accounting for age), binocular high-contrast VA (P
      < .001), and K-D testing (P < .001). Both groups demonstrated approximately 10-s
      improvements in MULES test times between trials 1 and 2 (P < .0001, paired t
      tests). CONCLUSION: The MULES test, a complex task of rapid picture naming
      involves an extensive visual network that captures eye movements, color
      perception and the characterization of objects. Color recognition, a key
      component of this novel assessment, is early in object processing and requires
      area V4 and the inferior temporal projections. MULES scores reflect performance
      of LCLA, a widely-used measure of visual function in MS clinical trials. These
      results provide evidence that the MULES test can add efficient visual screening
      to the assessment of patients with MS.

PMID- 30193156
TI  - Dynamizing nuclear actin filaments.
AB  - While it is long known that actin is part of the nuclear proteome, its properties
      and functions as regulated, functional and dynamically assembled actin filaments
      are only recently emerging. Thus, newly uncovered roles for intranuclear actin
      filaments are opening new perspectives on how the nucleus and its genomic content
      may be organized in particular with regard to a given stage of the cell cycle.
      Here, we summarize recent studies on actin filament polymerization and turnover
      within the nuclear compartment of mammalian cells. We emphasize and discuss novel
      findings, in which transient and dynamic nuclear actin filaments have been
      visualized in physiological contexts, and focus on aspects of signalling
      mechanisms, chromatin reorganization and DNA repair. Further, a better
      understanding of the spatiotemporal control of nuclear actin-regulating factors
      in mammalian cells will ultimately provide a more detailed view on how the
      nuclear F-actin cytoskeleton contributes to genome organization and nuclear
      architecture.

PMID- 30193155
TI  - All-trans retinoic acid ameliorates inflammatory response mediated by TLR4/NF
      kappaB during initiation of diabetic nephropathy.
AB  - Diabetic nephropathy (DN) is the leading cause of renal failure worldwide and its
      complications have become a public health problem. Inflammation, oxidative stress
      and fibrosis play central roles in the progression of DN that lead to renal
      failure. Potential deleterious effect of inflammation in early evolution of DN is
      not fully disclosed. Therefore, it is relevant to explore therapies that might
      modulate this process in order to reduce DN progression. We explored the
      beneficial effect of all-trans retinoic acid (ATRA) in early inflammation in
      glomeruli, proximal and distal tubules in streptozotocin (STZ)-induced diabetes.
      ATRA was administered (1 mg/kg daily by gavage) on days 3 to 21 after STZ
      administration. It was found that 21 days after STZ injection, diabetic rats
      exhibited proteinuria, increased natriuresis and loss of body weight. Besides,
      diabetes induced an increase in interleukins [IL-1beta, IL-1alpha, IL-16, IL-13,
      IL-2; tumor necrosis factor alpha (TNF-alpha)] and transforming growth factor
      beta 1 (TGF-beta1), chemokines (CCL2, CCL20, CXCL5 and CXCL7), adhesion molecules
      (ICAM-1 and L-selectin) and growth factors (GM-CSF, VEGF, PDGF) in glomeruli and
      proximal tubules, whereas ATRA treatment remarkably ameliorated these
      alterations. To further explore the mechanisms through which ATRA decreased
      inflammatory response, the NF-kappaB/p65 signaling mediated by TLR4 was studied.
      We found that ATRA administration attenuates the TLR4/NF-kappaB inflammatory
      signaling and prevents NF-kappaB nuclear translocation in glomeruli and proximal
      tubules.

PMID- 30193157
TI  - Regulation of actin dynamics by PI(4,5)P2 in cell migration and endocytosis.
AB  - The actin cytoskeleton is indispensable for several cellular processes, including
      migration, morphogenesis, polarized growth, endocytosis, and phagocytosis. The
      organization and dynamics of the actin cytoskeleton in these processes are
      regulated by Rho family small GTPases and kinase-phosphatase pathways. Moreover,
      membrane phospholipids, especially the phosphatidylinositol phosphates have
      emerged as important regulators of actin dynamics. From these, PI(4,5)P2 is the
      most abundant at the plasma membrane, and directly regulates the activities and
      subcellular localizations of numerous actin-binding proteins. Here, we discuss
      recent studies demonstrating that actin-binding proteins interact with PI(4,5)P2
      rich membranes through drastically different affinities and dynamics correlating
      with their roles in cytoskeletal dynamics. Moreover, by using mesenchymal cell
      migration and clathrin-mediated endocytosis as examples, we present a model for
      how interplay between PI(4,5)P2 and actin-binding proteins control the actin
      cytoskeleton in cells.

PMID- 30193158
TI  - Growth hormone activated STAT5 is required for induction of beige fat in vivo.
AB  - OBJECTIVE: The anti-obesity actions of growth hormone (GH) led us to investigate
      if GH signaling is able to regulate beige/brite fat development of white adipose
      tissue (WAT). METHODS: We studied WAT in GHR-391 mice engineered to be unable to
      activate STAT5 in response to GH, in mice with adipose specific deletion of GHR,
      in GHR-/- mice and in bGH transgenic mice. QPCR, immunoblots and
      immunohistochemistry were used to characterize WAT. The in vivo effects of beta-3
      adrenergic activation with CL-316,243 and that of FGF21 infusion were also
      studied. RESULTS: GHR-391 mice had lower surface temperature than WT, with
      deficiency in beta-oxidation and beiging transcripts including Ucp1. Oxidative
      phosphorylation complex subunit proteins were decreased dramatically in GHR-391
      inguinal white adipose tissue (iWAT), but increased in bGH iWAT, as were proteins
      for beige/brown markers. In accord with its lack of beta-3 adrenergic receptors,
      iWAT of GHR-391 mice did not beige in response to administration of the beta-3
      specific agonist CL-316,243 in contrast to WT mice. GHR-391 mice are deficient in
      FGF21, but unlike WT, infusion of the purified protein was without effect on
      extent of beiging. Finally, fat-specific deletion of the GHR replicated the loss
      of beiging associated transcripts. CONCLUSION: In addition to promoting
      lipolysis, our study suggests that GH is able to promote formation of beige
      adipose tissue through activation of STAT5 and induction of Adrb3. This
      sensitizes WAT to adrenergic input, and may contribute to the anti-obesity
      actions of GH.

PMID- 30193159
TI  - Place and community inclusion: Locational patterns of supportive housing for
      people with intellectual disability and people with psychiatric disorders.
AB  - PURPOSE: This study examines the locational patterns of publicly-funded
      supportive housing for people with intellectual disability (people with ID) and
      people with psychiatric disorders (people with PD). METHODS: Administrative data
      provided housing locations of 4599 people with ID and people with PD in one urban
      county and one suburban county in the United States. Census tract data captured
      neighborhood characteristics. Descriptive statistics and spatial analysis were
      used to analyze the distribution of supportive housing sites. RESULTS: People
      with ID were more dispersed across a larger number of census tracts with smaller
      number of residents per tract than people with PD. While spatial dispersion in
      favor of people with ID was consistent across both counties, difference in
      dispersion was more pronounced in the urban county. People with PD were
      concentrated in neighborhoods with more socio-economic disadvantage, more
      residential instability, and a higher level of race/ethnic diversity than people
      with ID. CONCLUSION: This study suggests that spatial-analytic method can serve
      as a useful tool for assessing the extent to which integrated housing is achieved
      for people with ID and people with PD. Interpretation of findings should be given
      due consideration of the policy context and neighborhood characteristics of the
      study communities.

PMID- 30193160
TI  - Walking on treadmill with Rett syndrome-Effects on the autonomic nervous system.
AB  - People with Rett syndrome have deficient central autonomic control, which may
      interfere with walking. We have limited knowledge regarding the effects of
      exertion during physical activity in Rett syndrome. The aim was to investigate
      the autonomic responses during walking on a treadmill in Rett syndrome. Twenty
      six females, 12 with Rett syndrome and 14 healthy females were included. All
      individuals started on the treadmill by standing still, followed by walking
      slowly with progressive speed until reaching maximum individual speed, which they
      kept for 6 min. Heart rate (HR), systolic (SBP), diastolic (DBP), mean arterial
      blood pressures (MAP), cardiac vagal tone (CVT), cardiac sensitivity to
      baroreflex (CSB), transcutaneous partial pressures of oxygen (pO2), carbon
      dioxide (pCO2), and breathing movements were recorded simultaneously and
      continuously. Autonomic responses were assessed by MAP, CSB and CVT during
      walking at 3 and 6 min. The changes in CSB and CVT in people with Rett syndrome
      compared to controls indicated more arousal, but only when the treadmill was
      started; as they continued walking, the arousal dropped to control level. People
      with Rett syndrome exhibited little changes in pCO2 whereas the controls showed
      increased values during walking. This suggests poor aerobic respiration in people
      with Rett syndrome during walking. Five people with Rett syndrome had Valsalva
      type of breathing at rest, three of those had normal breathing while walking on
      the treadmill while the remaining two started but soon stopped the Valsalva
      breathing during the walk. Our results show that individuals with Rett syndrome
      can walk for up to 6 min at their own maximum sustainable speed on a treadmill.
      Energy production may be low during walking in Rett syndrome, which could cause
      early tiredness. A treadmill can be used in people with Rett syndrome, but must
      be introduced slowly and should be individually tailored. We propose that walking
      promotes regular breathing in Rett syndrome.

PMID- 30193161
TI  - Critical review on engineering deaminases for site-directed RNA editing.
AB  - The game-changing role of CRISPR/Cas for genome editing draw interest to
      programmable RNA-guided tools in general. Currently, we see a wave of papers
      pioneering the CRISPR/Cas system for RNA targeting, and applying them for site
      directed RNA editing. Here, we exemplarily compare three recent RNA editing
      strategies that rely on three distinct RNA targeting mechanisms. We conclude that
      the CRISPR/Cas system seems not generally superior to other RNA targeting
      strategies in solving the most pressing problem in the RNA editing field, which
      is to obtain high efficiency in combination with high specificity. However, once
      achieved, RNA editing promises to complement or even outcompete DNA editing
      approaches in therapy, and also in some fields of basic research.

PMID- 30193162
TI  - Effects of modal shares on crash frequencies at aggregate level.
AB  - INTRODUCTION: Long-range transportation plans often involve proposals for
      improvements/ changes in different modes of travel. This means that modal share
      of trips generated at each traffic analysis zone (TAZ) by mode of travel needs to
      be predicted/ forecasted for safety evaluation purposes. The objective of this
      research study is to develop a series of aggregate crash prediction models
      (ACPMs) that relate with the modal split step of the conventional four-step
      demand models. METHOD: The models are developed utilizing network and vehicular,
      socio-economical, trip production/attraction and trip frequencies by mode at TAZ
      level as explanatory variables in a generalized linear regression with the
      assumption of a negative binomial error structure. Crash frequencies are split
      into total crashes (TC) and severe crashes (SC). RESULTS: The models prove
      promising in estimating crash frequencies upon changes in modal shares, which is
      essential in safety assessment of alternate transportation demand management
      (TDM) scenarios. Trips made in car, bus, and bus Service mode became significant
      in the estimated TC and trips made in car, taxi, school service, bus service and
      moped mode became significant in the estimated SC ACPMs. CONCLUSIONS: The ACPMs
      may be used from two different points of view. First and most appropriate use is
      to consider these as tools to forecast future crash frequencies and develop long
      term plans to counteract. In the second point of view, ACPMs act as the primary
      planning tool to identify how any increase in a specific mode-ridership will
      contribute to crash frequencies. This is of great interest in developing plans
      that involve increased use of a specific mode. PRACTICAL APPLICATION: As modal
      shares are forecasted in certain years into the future by the modal split step of
      demand modeling, crash frequencies could also be forecasted and safety
      implications of mobility improvement scenarios (e.g. increased number of trips by
      bus, car, etc.) would be evaluated.

PMID- 30193163
TI  - Microalgae cultivation and nutrients removal from sewage sludge after ozonizing
      in algal-bacteria system.
AB  - The feasibility of growing algae in concentrated wastewater generated from sludge
      ozonation for simultaneous nutrients removal and biomass production was studied.
      The effects of bacteria addition into microalgae on nutrients removal, biomass
      yield and settleability, the growth rate of algae and concentrations of
      extracellular polymeric substances (EPS) and soluble microbial products (SMP)
      were investigated. The results showed that the growth rate of algae in algal
      bacteria system (0.2182) was improved than in algae-only system (0.1852), while
      both of them are comparable with others reported previously. And the addition of
      bacteria enhanced COD, NH4+-N, TN and TP removal rate by 23.9 +/- 3.3%, 27.7 +/-
      3.6%, 16.6 +/- 1.8% and 14.9 +/- 2.2%, respectively. And 32.8 +/- 0.7% of the TN
      and 50.3 +/- 1.8% of the TP were recycled from ozonated sludge-supernatant (OSS)
      being absorbed into algal-bacterial biomass. The algal-bacteria system also
      demonstrated advantages on biomass settleability and heavy metals removal.
      Finally, the mechanism involving matter exchange and algal-bacteria system on OSS
      treatment in this study were discussed through evaluation of nutrients, SMP and
      EPS contents, nitrogen and phosphorus balance.

PMID- 30193164
TI  - Investigation on microbial community in remediation of lead-contaminated soil by
      Trifolium repensL.
AB  - Trifolium repensL. is a plant with strong adaptability and large biomass, which
      possess great potential for phytoremediation. However, little is known concerning
      its remediation effects and changes in rhizosphere microbial activity and
      community structure under heavy metal pressure. The aims of this study were to
      evaluate lead accumulation of Trifolium repensL., study microbial lead
      resistance, metabolism and community structure characteristics in rhizosphere
      soils. The accumulated Pb concentration of Trifolium repensL. was observed in 100
      and 500 mg/kg Pb contained soil at 55.81 and 90.3 mg/kg, respectively, which
      cause the decrease of acid-soluble fractions in rhizosphere soil. In the progress
      of lead-contaminated soil phytoremediation by Trifolium repensL., Pb resistance
      and metabolic activities of microorganisms have been prompted gradually. In
      addition, the microbial community composition and abundance were investigated
      using Illumina sequencing and quantitative PCR. The result showed that after
      phytoremediation, beneficial microorganisms, such as Flavisolibacter,
      Kaistobacter, and Pseudomonas, increased, becoming the dominant genera. This
      study has provided insight into the distribution and activity of the microbial
      community.

PMID- 30193165
TI  - Biosorption of copper, zinc, cadmium and chromium ions from aqueous solution by
      natural foxtail millet shell.
AB  - The industrial effluents discharge including heavy metals drain into the river,
      which has given rise to many problems of hazarding aquatic ecosystems and human
      health. Biosorption serves as the adsorption of heavy metals onto a natural
      adsorbent, it is becoming a potential alternative for toxic metals removal from
      industrial effluents in the last decades. The objectives of present research were
      to investigate the biosorption behaviors and the mechanisms of copper (Cu), zinc
      (Zn), cadmium (Cd) and chromium (Cr) ions, respectively onto foxtail millet shell
      as a new natural biosorbent in aqueous solution. The effects of pH (2.0-6.0),
      contact time (5.0-240.0 min), initial metal ions concentration (25.0-300.0 mg/L),
      particle size (0.25-2.0 mm) and biosorbent dosage (1.0-6.0 g/L) on the adsorption
      efficiency of the target metals using foxtail millet shell were evaluated in
      batch experiments. The models of isotherms and kinetics were used to assess the
      removal behaviors of Cu, Zn, Cd and Cr ions from aqueous solution by foxtail
      millet shell. The results showed that the best fitting equilibrium isotherm
      models for Cu, Zn, Cd and Cr ions were Freundlich (Cu and Zn) and Langmuir (Cd
      and Cr), respectively under the proper adsorption conditions. The maximum
      biosorption capacities were 11.89, 10.59, 12.48 and 11.70 mg g-1 of Cu, Zn, Cd
      and Cr, respectively by terms of Langmuir model. The kinetics of biosoption the
      target metal ions processes were best explained by pseudo-second-order kinetic
      model. Furthermore, pseudo-second-order and intraparticle diffusion models were
      cooperative mechanism during the whole biosorption. In addition, the pores on the
      surface of the shell were covered and then became smooth after biosorption
      through Scanning electron microscope (SEM) revealed, which demonstrated that the
      target metal ions were adsorbed by foxtail millet shell. The results of Energy
      dispersive spectrometer (EDS) further gave evidences that Cu, Zn, Cd and Cr ions
      were adsorbed onto surface of the adsorbent, respectively. Analysis of Fourier
      transform infrared spectroscopy (FTIR) demonstrated that various functional
      groups, such as C-H, C?O, C?C, C-O, O-S-O and Si-O groups were engaged in the
      interaction between foxtail millet shell and Cu, Zn, Cd and Cr ions. This paper
      provided evidences that foxtail millet shell was a potential and efficient
      biosorbent on removal of Cu, Zn, Cd and Cr ions from aqueous solutions, due to
      its high biosorption availability, capacity and low cost.

PMID- 30193166
TI  - Transcriptomic responses of Nile tilapia (Oreochromis niloticus) liver to
      environmental concentration of di(2-ethylhexyl)phthalate.
AB  - Di-(2-ethylhexyl) phthalate (DEHP) is currently the most frequently detected
      phthalic acid esters (PAEs) compounds and can induce diverse toxicities on
      aquatic organisms. To understand the molecular responses of fish to DEHP, we
      performed transcriptomic profiles in liver of tilapia (Oreochromis niloticus)
      which were exposed to environmental concentration of DEHP. A total of 30.10 Mb
      and 30.16 Mb clean reads were retrieved from the control and DEHP treated
      libraries, respectively. De-novo assembly of all the clean reads obtained 58,585
      unigenes. After comparing the two libraries, 2814 and 1790 genes were identified
      as significantly increased and depressed, respectively. Gene ontology (GO)
      classification system and Kyoto Encyclopedia of Genes and Genomes (KEGG) database
      analysis demonstrated that DEHP significantly disturbed the expression level of
      genes associated with immunity, endocrine and reproductive system, lipid
      metabolism and so on. Quantitative real-time PCR was performed to validate the
      results of RNA-sequencing (RNA-seq) analysis. The resulting data provide new
      insights for exploring the molecular basis of tilapia response to DEHP exposure.

PMID- 30193168
TI  - Molecular cloning, characterization, expression and enzyme activity of catalase
      from planarian Dugesia japonica in response to environmental pollutants.
AB  - Catalase (CAT) is an important antioxidant enzyme that protects aerobic organisms
      against oxidative damage by degrading hydrogen peroxide to oxygen and water. CAT
      mRNAs have been cloned from many species and employed as useful biomarkers of
      oxidative stress. In the present study, we cloned the cDNA sequence of CAT gene
      from freshwater planarian Dugesia japonica (designated as DjCAT) by means of RACE
      method. Sequence analysis and multiple alignment jointly showed that the full
      length cDNA sequence consists of 1734 nucleotides, encoding 506 amino acids.
      Three catalytic amino acid residues of His71, Asn144 and Tyr354, two CAT family
      signature sequences of a proximal active site signature (60FDRERIPERVVHAKGGGA77)
      and a heme-ligand signature motif (350RLFSYRDTQ358) are highly conserved,
      suggesting that the DjCAT belongs to the NADPH and heme-binding CAT family and
      has similar functions. In addition, the transcriptional level of CAT gene and
      activity of CAT enzyme upon acute exposure of environmental pollutants glyphosate
      and 1-decyl-3-methylimidazolium bromide ([C10mim]Br) were investigated
      systematically. The variation of CAT mRNA expression in D. japonica was
      quantified by real-time PCR and the results indicated that it was up-regulated
      after exposure to glyphosate or [C10mim]Br with a dose-dependent manner but not
      linearly. Even though the variation trend of CAT activity upon glyphosate stress
      was not monotonously increased and inconsistent with that after [C10mim]Br
      exposure on day 1 and 3 sampling time, with the duration prolonged to day 5 they
      both presented a dose-dependent increase and the differences achieved extreme
      significance in all treated groups compared to the control. These findings
      suggested that DjCAT plays an important role in antioxidant defense in D.
      japonica, and the mRNA expression of CAT would also be used as an effective
      biomarker to monitor the pollution in aquatic environment just like its
      corresponding enzyme.

PMID- 30193167
TI  - Differential effects of beta-glucan on oxidative stress, inflammation and copper
      transport in two intestinal regions of large yellow croaker Larimichthys crocea
      under acute copper stress.
AB  - The aim of the present study was to evaluate investigate the effects of beta
      glucan on oxidative stress, inflammation and copper transport in two intestinal
      regions of large yellow croaker under acute copper stress. Fish were injected
      with beta-glucan at a dose of 0 or 5 mg kg-1 body weight on 6, 4 and 2 days
      before exposed to 0 and 368 MUg Cu L-1 for 48 h. Biochemical indicators (MDA, Cu
      content, MTs protein levels, Cu/Zn-SOD, CAT and iNOS activities), gene
      expressions of oxidative stresses (Cu/Zn-SOD, CAT, Nrf2, MTs and MTF-1),
      inflammatory responses (NF-kappaB, iNOS, IL-1beta, IL-6 and TNF-alpha) and Cu
      transporters (ATP7A, ATP7B and CTR1) were determined. In the anterior intestine,
      beta-glucan increased MTs levels, activities of Cu/Zn-SOD, CAT and iNOS, mRNA
      levels of MTs, CAT, iNOS, ATP7A and ATP7B, and reduced Cu content and CTR1 gene
      expression to inhibite Cu-induced MDA. But beta-glucan had no effect on
      inflammatory gene expressions. In the mid intestine, beta-glucan increased
      activities of Cu/Zn-SOD and iNOS, mRNA levels of Cu/Zn-SOD, CAT and iNOS to
      maintain MDA content. However, unlike the anterior intestine, beta-glucan had no
      effect on Cu transporter gene expressions. Furthermore, transcription factors
      (Nrf2, NF-kappaB and MTF-1) paralleled with their target genes in the mid
      intestine, but no correlation was observed between NF-kappaB and IL-1beta and TNF
      alpha gene expressions in the anterior intestine. In conclusion, our results
      unambiguously showed that beta-glucan induced oxidative stress, inflammation and
      copper transport were varied between the anterior and mid intestines of fish
      under Cu stress.

PMID- 30193169
TI  - Whole-transcriptome response to wastewater treatment plant and stormwater
      effluents in the Asian clam, Corbicula fluminea.
AB  - The increase in human population and urbanization are resulting in an increase in
      the volume of wastewater and urban runoff effluents entering natural ecosystems.
      These effluents may contain multiple pollutants to which the biological response
      of aquatic organisms is still poorly understood mainly due to mixture toxicity
      and interactions with other environmental factors. In this context, RNA
      sequencing was used to assess the impact of a chronic exposure to wastewater
      treatment plant and stormwater effluents at the whole-transcriptome level and
      evaluate the potential physiological outcomes in the Asian clam Corbicula
      fluminea. We de-novo assembled a transcriptome from C. fluminea digestive gland
      and identified a set of 3,181 transcripts with altered abundance in response to
      water quality. The largest differences in transcriptomic profiles were observed
      between C. fluminea from the reference site and those exposed to wastewater
      treatment plant effluents. On both anthropogenically impacted sites, most
      differentially expressed transcripts were involved in signaling pathways in
      relation to energy metabolism such as mTOR and FoxO, suggesting an
      energy/nutrient deficit and hypoxic conditions. These conditions were likely
      responsible for damages to proteins and transcripts in response to wastewater
      treatment effluents whereas exposure to urban runoff might result in immune and
      endocrine disruptions. In absence of comprehensive chemical characterization, the
      RNAseq approach could provide information regarding the mode of action of
      pollutants and then be useful for the identification of which parameters must be
      studied at higher integration level in order to diagnose sites where the presence
      of complex and variable mixtures of chemicals is suspected.

PMID- 30193170
TI  - Olfactory groove and tuberculum sellae meningioma resection by endoscopic
      endonasal approach versus transcranial approach: A systematic review and meta
      analysis of comparative studies.
AB  - Intracranial meningiomas such as olfactory groove meningioma (OGM) and tuberculum
      sellae meningioma (TSM) arising at the anterior skull base are amenable to
      surgical resection. Traditionally, this has been achieved by transcranial
      approaches (TCAs), however, there has been an evolution in an endoscopic
      endonasal approach (EEA) within recent years. The aim of this systematic review
      and meta-analysis was to determine if the EEA was superior to the TCA in managing
      these anterior skull base meningioma based on comparative studies only, and
      highlight the limitations of the current literature. Searches of seven electronic
      databases from inception to April 2018 were conducted following Preferred
      Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines.
      There were 1479 articles identified for screening. Data were extracted and
      analyzed using meta-analysis of proportions. A total of 10 comparative studies
      satisfied criteria for inclusions. Resection by the EEA resulted in significantly
      less likelihood of worse vision (OR, 0.318; p = 0.039) when compared to TCA in
      OGM. However, EEA resulted also in significantly greater likelihoods of olfactory
      loss in OGM (OR, 4.511; p = 0.038) and TSM (OR, 3.075; p = 0.017), and CSF leak
      (OR, 3.854; p = 0.013) in TSM. In terms of surgical and prognosis outcomes, there
      was no statistically significant trend in favor of either approach in OGM or TSM.
      The EEA appears to confer a different postoperative complication profile when
      compared to the TCA in resecting OGM vs TSM which validates previous case-series
      comparisons. There is a need for longer-term studies that are larger,
      prospective, randomized in order to fully elucidate efficacy given slow tendency
      for progression of meningioma in order to develop a more rigorous approach
      selection algorithm.

PMID- 30193171
TI  - Organ donation education in the ICU setting: a qualitative and quantitative
      analysis of family preferences.
AB  - PURPOSE: Determine family-centered methods of providing organ donation education
      to families in ICU waiting rooms. MATERIALS AND METHODS: We performed a
      qualitative analysis of semi-structured interviews and quantitative analysis of
      paper surveys of family members of 118 ICU patients in the acute ICU setting.
      RESULTS: Twelve interviews and 152 surveys (66% response rate) were completed.
      Respondents' knowledge of organ donation processes was incomplete: only 32%
      answered all of four questions about donation correctly. No significant
      correlation was found between respondents' objective knowledge scores and their
      self-reported donation knowledge (rho = 0.07, p = .46). Seventy-five percent of
      respondents (110/147) thought receiving donation information during the ICU stay
      would aid their decision-making regarding donation. The most preferred methods of
      receiving information were via a website link (94% positive or neutral response)
      or brochures in the waiting room (89% positive or neutral), while the least
      preferred methods were having brochures in the ICU admission packet (24%
      negative) and a poster in the ICU waiting room (22% negative). CONCLUSIONS: ICU
      families desire accurate information about organ donation, and are receptive to
      its provision in the acute ICU setting. Family-centered approaches to information
      delivery may enhance understanding of organ donation processes and aid decision
      making about organ donation.

PMID- 30193172
TI  - A feasibility study to assess pre-admission status and six month outcomes of
      major trauma patients admitted to an intensive care unit, using the WHO DAS 2.0.
AB  - PURPOSE: To report the feasibility of assessing pre-admission functional status
      of ICU trauma patients, with repeat assessment at six months post ICU discharge
      using a standardised measure. MATERIALS AND METHODS: A prospective longitudinal
      observational cohort design recruited consecutive adult major trauma admissions
      to a UK general ICU, between 1st November 2016 and 1st November 2017. The 12-item
      World Health Organisation Disability Schedule 2.0 was completed to assess pre
      admission functional status as soon as possible after ICU admission. This was
      repeated at six months post ICU discharge, through ICU follow-up clinic, by post,
      or by telephone. RESULTS: The ICU physiotherapy team were trained in the use of
      the measure in 2.5 h. Initial assessments were completed for 57 participants.
      Mean time from admission to assessment was 38 h, with assessments completed in an
      average of three minutes. The median six month score was 28.5, increasing from
      baseline by a median of 15.5 points. Of the responses received 20 (65%) were via
      post, 4 (13%) by telephone, and 7 (23%) via follow-up clinic. CONCLUSIONS:
      Standardised assessment of pre-admission function was feasible. Future research
      should investigate the clinical relevance of scores and the validity of the
      measure in trauma patients.

PMID- 30193173
TI  - Transcriptome of the Wistar audiogenic rat (WAR) strain following audiogenic
      seizures.
AB  - The Wistar Audiogenic Rat (WAR) is a model whose rats are predisposed to develop
      seizures following acoustic stimulation. We aimed to establish the
      transcriptional profile of the WAR model, searching for genes that help in
      understanding the molecular mechanisms involved in the predisposition and
      seizures expression of this strain. RNA-Seq of the corpora quadrigemina of WAR
      and Wistar rats subjected to acoustic stimulation revealed 64 genes
      differentially regulated in WAR. We validated twelve of these genes by qPCR in
      stimulated and naive (non-stimulated) WAR and Wistar rats. Among these, Acsm3 was
      upregulated in WAR in comparison with both control groups. In contrast, Gpr126
      and Rtel1 were downregulated in naive and stimulated WAR rats in comparison with
      the Wistar controls. Qdpr was upregulated only in stimulated WAR rats that
      exhibited audiogenic seizures. Our data show that there are genes with
      differential intrinsic regulation in the WAR model and that seizures can alter
      gene regulation. We identified new genes that might be involved in the epileptic
      phenotype and comorbidities of the WAR model.

PMID- 30193174
TI  - Single-payer or a multipayer health system: a systematic literature review.
AB  - OBJECTIVES: Healthcare systems worldwide are actively exploring new approaches
      for cost containment and efficient use of resources. Currently, in a number of
      countries, the critical decision to introduce a single-payer over a multipayer
      healthcare system poses significant challenges. Consequently, we have
      systematically explored the current scientific evidence about the impact of
      single-payer and multipayer health systems on the areas of equity, efficiency and
      quality of health care, fund collection negotiation, contracting and budgeting
      health expenditure and social solidarity. STUDY DESIGN: This is a systematic
      review based on Preferred Reporting Items for Systematic Reviews and Meta
      Analyses (PRISMA) guidelines. METHODS: A search for relevant articles published
      in English was performed in March 2015 through the following databases: Excerpta
      Medica Databases, Cumulative Index of Nursing and Allied Health Literature,
      Medical Literature Analysis and Retrieval System Online through PubMed and Ovid,
      Health Technology Assessment Database, Cochrane database and WHO publications. We
      also searched for further articles cited by eligible papers. RESULTS: A total of
      49 studies were included in the analysis; 34 studied clinical outcomes of
      patients enrolled in different health insurances, while 15 provided a qualitative
      assessment in this field. CONCLUSION: The single-payer system performs better in
      terms of healthcare equity, risk pooling and negotiation, whereas multipayer
      systems yield additional options to patients and are harder to be exploited by
      the government. A multipayer system also involves a higher administrative cost.
      The findings pertaining to the impact on efficiency and quality are rather
      tentative because of methodological limitations of available studies.

PMID- 30193175
TI  - Risk attitudes of people with 'manageable' chronic disease: An analysis under
      prospect theory.
AB  - Health promotion interventions can be improved using methods from behavioural
      economics to identify and target specific decision-making biases at the
      individual level. In this context, prospect theory provides a suitable framework
      within which decision-making processes can be operationalised. Focusing on a
      trade-off between health outcomes and behaviour change incurred by chronic
      disease management (lifestyle change, or 'self-management'), we are the first to
      measure the risk attitudes and quantify the full utility function under prospect
      theory of a patient population. We conducted a series of hypothetical
      elicitations over health outcomes associated with different self-management
      behaviours from a population of individuals with or without 'manageable' chronic
      disease (n = 120). We observed risk aversion in both the gain and the loss
      domains, as well as significant loss aversion. There seems to be an age effect on
      risk attitudes in this context, with younger people being on average less risk
      averse than older people. Our work addresses a need to better understand these
      decision-making processes, so that behaviour change interventions tailored to
      specific patient populations can be improved.

PMID- 30193176
TI  - Changes in postural sway and gait characteristics as a consequence of anterior
      load carriage.
AB  - BACKGROUND: Anterior load carriage represents a common daily and occupational
      activity. Carrying loads in front of the body could potentially increase
      instability during standing and walking. RESEARCH QUESTION: This study examined
      the effects of anterior load carriage on postural sway and gait parameters in
      healthy adults. METHODS: Twenty-nine participants (19 males, 10 females, age =
      33.8 +/- 12.7 years, height = 1.73 +/- 0.07 m, mass = 75.1 +/- 13.7 kg) were
      assessed in four conditions; (1) carrying no load (CON), (2) carrying a load with
      no added weight (i.e. empty box), (3) carrying a load with 5% body mass, and (4)
      carrying a load with 10% body mass. Anteroposterior and mediolateral centre of
      pressure (COP) displacement (cm) and the mean COP velocity (cm s-1) were used to
      characterise postural sway. Coefficient of variation of the stride length, stride
      time and double support time were calculated from 1 min of treadmill walking at a
      preferred pace for gait assessment. RESULTS: The addition of the 10% load
      elicited an increase in anteroposterior COP displacement when compared to CON (d
      = 1.59), 0% (d = 1.50), and 5% (d = 0.75) (P < 0.001). The addition of the 10%
      load increased stride time (d = 1.71) and stride length (d = 1.20) variability
      when compared to CON (P < 0.001). SIGNIFICANCE: In summary, the increase in
      postural sway and gait variability with added weight is dependent on the
      magnitude of the load, where the greater the load, the greater the effect on
      static and dynamic stability. Anterior load carriage potentially increases the
      risk of fall-related injuries.

PMID- 30193177
TI  - Arabidopsis group XIV ubiquitin-conjugating enzymes AtUBC32, AtUBC33, and AtUBC34
      play negative roles in drought stress response.
AB  - AtUBC32, AtUBC33, and AtUBC34 comprise Arabidopsis group XIV E2 ubiquitin
      conjugating enzymes. Yeast two-hybrid, in vitro pull-down, and bimolecular
      fluorescence complementation assays revealed that group XIV E2s are interacting
      partners of the U-box-type E3 ligase PUB19, a negative regulator of drought
      stress response. These three AtUBCs are co-localized with PUB19 to the punctae
      like structures, most of which reside on the endoplasmic reticulum membrane of
      tobacco leaf cells. Suppression of AtUBC32, AtUBC33, and AtUBC34 resulted in
      increased abscisic acid-mediated stomatal closure and tolerance to drought
      stress. These results indicate that Arabidopsis group XIV E2s play negative roles
      in drought stress response.

PMID- 30193178
TI  - Rural dwellers are less likely to survive cancer - An international review and
      meta-analysis.
AB  - BACKGROUND: Existing research from several countries has suggested that rural
      dwellers may have poorer cancer survival than urban-dwellers. However, to date,
      the global literature has not been systematically reviewed to determine whether a
      rural cancer survival disadvantage is a global phenomenon. METHODS: Medline,
      CINAHL, and EMBASE were searched for studies comparing rural and urban cancer
      survival. At least two authors independently screened and selected studies. We
      included epidemiological studies comparing cancer survival between urban and
      rural residents (however defined) that also took socioeconomic status into
      account. A meta-analysis was conducted using 11 studies with binary rural:urban
      classifications to determine the magnitude and direction of the association
      between rurality and differences in cancer survival. The mechanisms for urban
      rural cancer survival differences reported were narratively synthesised in all 39
      studies. FINDINGS: 39 studies were included in this review. All were
      retrospective observational studies conducted in developed countries. Rural
      dwellers were significantly more likely to die when they developed cancer
      compared to urban-dwellers (HR 1.05 (95% CI 1.02 - 1.07). Potential mechanisms
      were aggregated into an ecological model under the following themes: Patient
      Level Characteristics; Institutions; Community, Culture and Environment; Policy
      and Service Organization. INTERPRETATION: Rural residents were 5% less likely to
      survive cancer. This effect was consistently observed across studies conducted in
      various geographical regions and using multiple definitions of rurality. High
      quality mixed-methods research is required to comprehensively evaluate the
      underlying factors. We have proposed an ecological model to provide a coherent
      framework for future explanatory research. FUNDING: None.

PMID- 30193179
TI  - Discrimination between HCV29 and T24 by controlled proliferation of cells co
      cultured on substrates with different elasticity.
AB  - In this work the impact of substrate elasticity on the proliferation of two cell
      lines, a non-malignant transitional epithelium HCV-29 and a bladder transitional
      cell carcinoma T24 cultured individually and in co-culture was analyzed. A
      significantly stronger, highly cell-dependent impact of mechanical properties on
      cellular behavior was shown for cells co-cultured from the mixture. A more
      effective proliferation process observed for T24 cells was analyzed
      quantitatively for asymmetric HCV29: T24 mixtures co-cultured on soft substrate.
      The obtained results suggest that the proliferation of T24 cells is even 4 times
      more effective as compared to HCV29 cells and confirm strong invasiveness of
      metastatic T24 cells. The high adaptiveness of T24 cells to adverse environmental
      conditions enables easy and accurate discrimination between not isolated healthy
      and cancer cells.

PMID- 30193180
TI  - Jointly modified mechanical properties and accelerated hydrolytic degradation of
      PLA by interface reinforcement of PLA-WF.
AB  - Polylactic acid (PLA), one of the most likely green and environmentally friendly
      materials, is an alternative to petroleum-based plastic. It still remains a
      challenge to increase the degradation rate and decrease the cost of PLA without
      compromised mechanical properties. Low cost PLA/wood flour (WF) composite was
      elaborately designed and fabricated with improved interface compatibility through
      the introducing of polymethyl methacrylate (PMMA). The result indicated that
      compared with that of neat PLA, the tensile strength and bending strength of
      PLA/WF/PMMA (8:2) (80 wt% of the PLA, 20 wt% of WF and PMMA (8:2)) were increase
      by 4.60% and 26.54% respectively. Through the hydrolysis experiments combined
      with the SEM analysis, the main reason for the improvement of the mechanical
      properties of composite materials was that PMMA makes continuous three-phase
      composition, and interface compatibility of PLA and WF with overly different
      polarity was modified. Meanwhile, the hydrolysis rate of PLA/WF/PMMA was much
      faster than that of PLA. Finally, there was a more significant discovery that the
      addition of PMMA changed material degradation mechanism, and it was why to
      efficiently accelerate the degradation rate of the material. This will provide a
      new inspiration for PLA degradation research, and a fresh perspective is to be
      given other materials.

PMID- 30193181
TI  - Effects of artificial aging and progression of cracks on thin occlusal veneers
      using SD-OCT.
AB  - OBJECTIVES: The purpose of this study was to evaluate the effects of artificial
      aging on thin glass-ceramic occlusal premolar veneers, adhesively bonded to
      dentin, by examining the changes caused by artificial aging using spectral domain
      optical coherence tomography (SD-OCT). In addition, the development of cracks in
      the ceramic veneers and their possible influence on the behavior of the ceramic
      restorations were examined. METHODS: In total, 48 extracted sound upper premolars
      were prepared in the dentin for occlusal veneers milled from lithium disilicate
      ceramic blocks (IPS e.max CAD, Ivoclar Vivadent, Liechtenstein). All restorations
      were adhesively bonded using resin cement (Variolink Esthetic DC, Ivoclar
      Vivadent). Specimens were 3-dimensionally and 2-dimensionally imaged by SD-OCT
      (Telesto II, Thorlabs GmbH, Germany), then subjected to thermal-dynamic loading
      in a chewing simulator with 1,200,000 cycles at a load of 10 kg. Specimens were
      2D and 3D imaged again after the artificial aging. Finally, they were subjected
      to quasi-static loading using a universal testing machine until failure occurred
      and later examined microscopically to assess the mode of failure. ANOVA test was
      performed for statistical analysis of data and Tukey's post-hoc test was used to
      compare the groups at 5% significance level. Chi-Square Test and Fischer's Exact
      Test of Independence were conducted to test the association between nominal
      variables. RESULTS: No changes or irregularities were observed in the cement
      layer or tooth substrate after the aging process. However, wear of the ceramic
      was noticed at the surface of contact with the antagonist during the test. The
      development of cracks was detected in 23% of the specimens. Cracks did not affect
      the fracture strength (p > 0.05) but influenced the mode of failure (p <= 0.001).
      SIGNIFICANCE: Optical coherence tomography allows an easy and non-invasive method
      to internally scan teeth and restorations. Development of cracks in the ceramic
      did not affect the fracture strength of the restorations but might lead to a more
      catastrophic type of failure.

PMID- 30193182
TI  - Mechanical and biological performance of axially loaded novel bio-nanocomposite
      sandwich plate-type implant coated by biological polymer thin film.
AB  - Post-surgical infection is one of the essential problems in bone scaffolds that
      is usually treated with antibiotics. This issue may be related to the poor blood
      supply for bone tissue due to high concentrations of drug. In the current study,
      the effect of zinc oxide (ZnO) nanoparticles on the antibacterial behavior of the
      nanocrystalline hydroxyapatite (n-HA) scaffolds coated by gelatin-ibuprofen (GN
      IBO) is evaluated. To this end, the bio-nanocomposite scaffolds are fabricated
      via the space holder technique and then characterized with the aid of X-ray
      diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR) and scanning
      electron microscopy (SEM). The compressive strength, fracture toughness,
      porosity, elastic modulus as the mechanical properties, and the apatite
      formation, biodegradation, drug release and wettability beside the roughness as
      the biological properties are predicted. The obtained experimental results
      indicate that the bio-nanocomposite scaffolds containing 10 wt% ZnO has suitable
      mechanical and biological properties. After that, an analytical model is
      developed to predict the nonlinear instability and vibration responses of an
      axially loaded sandwich plate-type implants made of the fabricated n-HA-ZnO bio
      nanocomposites coated by GN-IBO thin film corresponding to various weight
      fractions of ZnO nanoparticles. It is found that ZnO peaks in the positions of
      2theta are equal to 31.6 degrees , 33.6 degrees , 34 degrees , 46.4 degrees , and
      62 degrees , which represent the crystalline characteristics. Also, it is
      revealed that through addition of ZnO nanoparticles, the hardness and elastic
      modulus as well as the bone formation and biodegradation rate of the bio
      nanocomposite scaffold enhance, while its drug release in the phosphate buffer
      solution detected with UV spectrum reduces. It is found that by increasing the
      ZnO weight fraction, the critical axial buckling load of the sandwich bio
      nanocomposite implant enhances, and it buckles at lower axial shortening.
      However, it is seen that for higher value of wt% ZnO, its influence on the
      critical buckling load decreases.

PMID- 30193183
TI  - Site-directed mutagenesis of cysteine residues alters oxidative stability of
      fetal hemoglobin.
AB  - Redox active cysteine residues including betaCys93 are part of hemoglobin's
      "oxidation hotspot". Irreversible oxidation of betaCys93 ultimately leads to the
      collapse of the hemoglobin structure and release of heme. Human fetal hemoglobin
      (HbF), similarly to the adult hemoglobin (HbA), carries redox active gammaCys93
      in the vicinity of the heme pocket. Site-directed mutagenesis has been used in
      this study to examine the impact of removal and/or addition of cysteine residues
      in HbF. The redox activities of the recombinant mutants were examined by
      determining the spontaneous autoxidation rate, the hydrogen peroxide induced
      ferric to ferryl oxidation rate, and irreversible oxidation of cysteine by
      quantitative mass spectrometry. We found that substitution of gammaCys93Ala
      resulted in oxidative instability characterized by increased oxidation rates.
      Moreover, the addition of a cysteine residue at alpha19 on the exposed surface of
      the alpha-chain altered the regular electron transfer pathway within the protein
      by forming an alternative oxidative site. This may also create an accessible site
      for di-sulfide bonding between Hb subunits. Engineering of cysteine residues at
      suitable locations may be useful as a tool for managing oxidation in a protein,
      and for Hb, a way to stave off oxidation reactions resulting in a protein
      structural collapse.

PMID- 30193185
TI  - Variations in the breast reconstruction rate in France: A nationwide study of
      19,466 patients based on the French medico-administrative database.
AB  - BACKGROUND: Access to breast reconstruction (BR) surgery after a mastectomy
      remains limited, with a large degree of national and international variation
      despite its known psychological benefits and impact on quality of life. The aim
      of this study was to investigate the factors influencing breast reconstruction in
      France where cancer-related healthcare costs are fully reimbursed. METHODS: All
      primary mastectomies for breast carcinoma performed in 2012 and linked BR
      surgeries from 2012 to December 2015 were extracted from the French medico
      administrative database. A three-level logistic regression analysis was performed
      to model the probability of breast reconstruction according to patient, hospital
      and administrative region characteristics. RESULTS: Among the 19,466 women who
      had a mastectomy in 2012, 5328 (27.4%) had breast reconstruction. Multivariate
      analysis showed that the BR rate was lower in patients living in an area with an
      unfavourable socioeconomic level (p < .001), in low volume hospitals (p < .001),
      and in public hospitals (18.6%) compared to private hospitals (25.9%), university
      hospitals (29.8%), and cancer centres (35.0%) (p < .001). BR rate was
      significantly lower in patients older than 65 compared to those younger (7.5%
      versus 42.1%, p < .001). The impact of age was even greater in public hospitals
      than in other centres (interaction test, p = .001). We also observed significant
      heterogeneity in the BR rate across regions, which could be partially explained
      by differences in the plastic surgeon density. CONCLUSIONS: Breast reconstruction
      rate heterogeneity could be attributed to women choice. However, our study
      suggests that unequal access to high-quality procedures also plays a role,
      particularly for older breast cancer women.

PMID- 30193186
TI  - SAVI SCOUT(r) localization of breast lesions as a practical alternative to wires:
      Outcomes and suggestions for trouble-shooting.
AB  - OBJECTIVE: The purpose of our study was to determine the frequency of successful
      SAVI SCOUT(r) localizations, to identify the factors contributing to unsuccessful
      procedures, and to provide a problem-solving algorithm to address those factors.
      SUBJECTS AND METHODS: This retrospective study was performed following IRB
      approval. We included all consecutive patients with SCOUT(r) reflector placement
      performed at a single tertiary-care cancer center. Each case was reviewed and the
      following data were recorded: patient age, breast density, localization target,
      imaging modality used for guidance, post procedure mammogram reflector to skin
      and reflector to target distances, presence of the reflector in the specimen
      radiograph, excisional biopsy pathology and any procedure complications. RESULTS:
      In 129 women, 152 SAVI SCOUT(r) reflectors were placed. Most patients had only 1
      reflector placed, but 19 (15%) women had multiple reflectors placed for the
      purposes of bracketing, multiple excisions in 1 breast, bilateral excisions, or
      any combination thereof. The most common target was a mass (65%) and the most
      common modality for guidance was ultrasound (73%). SAVI SCOUT(r) localization was
      successful in 97%of reflectors, including 89% of reflectors targeting axillary
      lymph nodes. The most common failure encountered was the inability to obtain a
      signal in the radiology suite, due to (1) excessive target depth for the
      radiology suite handpiece and console, (2) obscuration by a hematoma, or (3)
      faulty reflector. No post-operative complications occurred. CONCLUSION: The SAVI
      SCOUT(r) surgical guidance system is an accurate and reliable method for
      localization of non-palpable breast lesions, bracketing, and axillary lymph
      nodes.

PMID- 30193184
TI  - Real-time visualization of oxidative stress-mediated neurodegeneration of
      individual spinal motor neurons in vivo.
AB  - Generation of reactive oxygen species (ROS) has been shown to be important for
      many physiological processes, ranging from cell differentiation to apoptosis.
      With the development of the genetically encoded photosensitiser KillerRed (KR) it
      is now possible to efficiently produce ROS dose-dependently in a specific cell
      type upon green light illumination. Zebrafish are the ideal vertebrate animal
      model for these optogenetic methods because of their transparency and efficient
      transgenesis. Here we describe a zebrafish model that expresses membrane-targeted
      KR selectively in motor neurons. We show that KR-activated neurons in the spinal
      cord undergo stress and cell death after induction of ROS. Using single-cell
      resolution and time-lapse confocal imaging, we selectively induced
      neurodegeneration in KR-expressing neurons leading to characteristic signs of
      apoptosis and cell death. We furthermore illustrate a targeted microglia response
      to the induction site as part of a physiological response within the zebrafish
      spinal cord. Our data demonstrate the successful implementation of KR mediated
      ROS toxicity in motor neurons in vivo and has important implications for studying
      the effects of ROS in a variety of conditions within the central nervous system,
      including aging and age-related neurodegenerative diseases, such as Alzheimer's
      disease, Parkinson's disease and amyotrophic lateral sclerosis.

PMID- 30193187
TI  - Optimized categorization algorithm of coronary artery calcification score on non
      gated chest low-dose CT screening using iterative model reconstruction technique.
AB  - OBJECTIVES: To investigate the optimized categorization algorithm of coronary
      artery calcification score (CACS) for more accurate risk assessment on non-gated
      chest low-dose CT (LDCT) screening using iterative model reconstruction (IMR)
      technique. METHODS: We enrolled 102 patients who required coronary artery CTA
      examination and had coronary artery calcification (CAC) in this study. The CACS
      on non-gated LDCT and ECG-gated CT images were both measured by Agatston analysis
      software on Philips workstation. RESULTS: According to the original algorithm (1
      100, 100-400 and >400), the CACS measured by non-gated LDCT scan showed a good
      agreement with ECG-gated CT scan (weighted kappa value of 0.602, P < 0.05). Two
      ROC curves were drawn to evaluate the accuracy of CACS categorization. The cutoff
      values were 87.44 and 255.26 respectively. Based on the best diagnostic cutoff
      value, the CACS measured by the non-gated LDCT scan showed an excellent agreement
      with ECG-gated CT scan (weighted kappa value of 0.781, P < 0.05). CONCLUSIONS:
      The CACS on non-gated LDCT may have been underestimated. We therefore developed
      an optimized categorization algorithm of non-gated CACS in this study.

PMID- 30193188
TI  - Economic status, air quality, and child health: Evidence from inversion episodes.
AB  - Normally, the temperature decreases with altitude, allowing air pollutants to
      rise and disperse. During inversion episodes, warmer air at higher altitude traps
      air pollutants at the ground. By merging vertical temperature profile data from
      NASA with pollution monitors and health care records, we show that inversions
      increase the PM10 levels by 25% and children's respiratory health problems by
      5.5%. Low-income children are particularly affected, and differences in baseline
      health seem to be a key mediating factor behind the effect of pollution on the
      SES health gap. Policies that improve dissemination of information on inversion
      status may hence improve child health, either through private action or via
      policies that curb emissions during inversion episodes.

PMID- 30193190
TI  - MicroRNA-124-3p inhibits collagen synthesis in atherosclerotic plaques by
      targeting prolyl 4-hydroxylase subunit alpha-1 (P4HA1) in vascular smooth muscle
      cells.
AB  - BACKGROUND AND AIMS: Collagen synthesis in vascular smooth muscle cells (VSMCs)
      is very important in atherosclerosis, as it affects plaque stability. In this
      study, we aim to assess whether miR-124-3p is involved in the collagen synthesis
      process in VSMCs and the role it might play in atherosclerotic development.
      METHODS: We modulated the miR-124-3p expression in the aortic root plaques of
      high-fat-diet fed ApoE-/- mice by lentivirus injection. To determine plaque size
      and the content of plaque-stability-related cells or molecules, stainings,
      including hematoxylin and eosin, Oil red O, Sirius Red and immunohistochemical
      staining, were performed. Fluorescence in situ hybridization (FISH) was used to
      locate miR-124-3p in atherosclerotic plaques. Western blotting and RT-qPCR were
      carried out to determine the level of P4HA1 as well as type I and type III
      collagen protein and mRNA expression. RESULTS: Results showed that collagen and
      VSMC content of plaques was inversely correlated with miR-124-3p levels. By FISH,
      we identified that miR-124-3p was primarily expressed by VSMCs. We also found
      that protein levels of type I and type III collagen in aortas and atherosclerotic
      plaques were decreased by miR-124-3p. We modulated miR-124-3p level in vitro and
      found it could inhibit collagen expression in HASMCs. This might be caused by the
      downregulation of P4HA1. P4HA1 was predicted as miR-124-3p's direct target, which
      was verified with a dual luciferase reporter assay and RIP test. CONCLUSIONS: The
      results presented here provide evidence that miR-124-3p inhibits VSMC collagen
      synthesis by directly targeting P4HA1, which might decrease atherosclerotic
      plaque stability.

PMID- 30193189
TI  - Brain neurokinin-1 receptor availability in never-medicated patients with major
      depression - A pilot study.
AB  - BACKGROUND: Neurotransmitter substance P (SP) and its preferred neurokinin-1
      receptor (NK1R) have been implicated in the treatment of affective and addiction
      disorders. Despite promising preclinical data on antidepressant action, the
      clinical trials of NK1R antagonists in major depression have been disappointing.
      There are no direct in vivo imaging studies on NK1R characteristics in patients
      with a major depressive disorder (MDD). METHODS: In this cross-sectional case
      control study, we recruited nine never-medicated patients with moderate to severe
      MDD and nine matched healthy controls. NK1R availability (NK1R binding potential,
      BPND) was measured with in vivo 3-D positron emission tomography and a specific
      NK1 receptor tracer [18F]SPA-RQ. Clinical symptoms were assessed with the 17-item
      Hamilton Rating Scale for Depression (HAM-D17). RESULTS: NK1R-BPND did not differ
      statistically significantly between patients with MDD and healthy controls. HAM
      D17 total scores (range 21-32) correlated positively with NK1R-BPND in cortical
      and limbic areas. HAM-D17 subscale score for anxiety symptoms correlated
      positively with NK1R-BPND in specific brain areas implicated in fear and anxiety.
      LIMITATIONS: Small sample size. Low variability in the clinical HAM-D subscale
      ratings may affect the observed correlations. CONCLUSIONS: Our preliminary
      results do not support a different baseline expression of NK1Rs in a
      representative sample of never-medicated patients with MDD during a current
      moderate/severe depressive episode. The modulatory effect of NK1Rs on affective
      symptoms is in line with early positive results on antidepressant action of NK1
      antagonists. However, the effect is likely to be too weak for treatment of MDD
      with NK1R antagonists alone in clinical practice.

PMID- 30193191
TI  - The electrical activity map of the human skin indicates strong differences
      between normal and diabetic individuals: A gateway to onset prevention.
AB  - The human skin is not only the largest organ, but also the most important
      candidate for novel non-invasive methods of investigation. Here we describe a
      large-scale prototype for determining the real-time distribution of the
      electrical activity from the surface of the human skin. A collection of 200
      sensors have been placed across the entire trunk surface. The output of each
      sensor was remotely inserted into a 20 * 10 LED matrix for a parallel capture of
      the signals. Continuous observations of the electrical activity pattern were made
      above the LED matrix by a digital camera in an obscure environment. A total of
      5.2 million measurements (25,920 maps) have been recorded as light intensities
      from the LED matrix and converted into percentages for evaluation. A total of 36
      individuals were divided equally into two groups and subjected to a short glucose
      tolerance test for 1 h; one group with established Type 2 Diabetes (T2D) and the
      other group without diabetes. The electrical activity pattern and the average
      signal intensity of normal individuals (37% +/- 8.1) and diabetic individuals
      (58% +/- 7.8), showed a significant difference of 21%. The average signal
      intensity on the ventral side (VS) and dorsal side (DS) of the torso exhibited
      different behaviors in diabetics and non-diabetics. On average, diabetic
      individuals have shown an electrical activity of higher intensity on DS (DS =
      60%, VS = 55%), while the normal group has shown a higher intensity on VS (DS =
      36%, VS = 39%).

PMID- 30193192
TI  - Removal of trace organic chemicals in wastewater effluent by UV/H2O2 and UV/PDS.
AB  - In this study, we comparatively investigated the degradation of 12 trace organic
      chemicals (TOrCs) during UV/H2O2 and UV/peroxydisulfate (PDS) processes. Second
      order rate constants for the reactions of iopromide, phenytoin, caffeine,
      benzotriazole, and primidone with sulfate radical (SO4*-) were determined for the
      first time. Experiments were conducted in buffered pure water and wastewater
      effluent with spiked TOrCs. UV/PDS degraded all TOrCs more efficiently than
      UV/H2O2 in buffered pure water due to the higher yield of SO4*- than that of
      hydroxyl radical (*OH) at the same initial molar dose of PDS and H2O2,
      respectively. UV/PDS showed higher selectivity toward TOrCs removal than UV/H2O2
      in wastewater effluent. Compounds with electron-rich moieties, such as
      diclofenac, venlafaxine, and metoprolol, were eliminated faster in UV/PDS whereas
      UV/H2O2 was more efficient in degrading compounds with lower reactivity to SO4*-.
      The fluence-based rate constants ( [Formula: see text] ) of TOrCs in wastewater
      effluent linearly increased as a function of initial H2O2 dose during UV/H2O2,
      possibly due to the constant scavenging impact of the wastewater matrix on *OH.
      However, exponential increase of kobs-UV/PDS with increasing PDS dose was
      observed for most compounds during UV/PDS, suggesting the decreasing scavenging
      effect of the water matrix (electron-rich site of effluent organic matter (EfOM))
      after initial depletion of SO4*- at low PDS dose. Fulvic and humic-like
      fluorophores appeared to be more persistent during UV/H2O2 compared to aromatic
      protein and soluble microbial product-like fluorophores. In contrast, UV/PDS
      efficiently degraded all identified fluorophores and showed less selectivity
      toward the fluorescent EfOM components. Removal pattern of TOrCs during pilot
      scale UV/PDS was consistent with lab-scale experiments, however, overall removal
      rates were lower due to the presence of higher concentration of EfOM and nitrite.

PMID- 30193193
TI  - Removal of antibiotic residues, antibiotic resistant bacteria and antibiotic
      resistance genes in municipal wastewater by membrane bioreactor systems.
AB  - Antibiotic residues, antibiotic resistant bacteria (ARB) and antibiotic
      resistance genes (ARGs) are considered new classes of water contaminants due to
      their potential adverse effects on aquatic ecosystems and human health. This
      paper provides comprehensive data on the occurrences of 19 antibiotics, bacteria
      resistant to 10 antibiotics, and 15 ARGs in raw influent and different treatment
      stages of conventional activated sludge (CAS) and membrane bioreactor (MBR)
      systems. Seventeen out of the 19 target antibiotics were detected in raw influent
      with concentrations of up to ten micrograms per liter. Concentrations of
      antibiotics measured in the secondary effluent were much lower compared to those
      in the raw influent. Among the antibiotics, amoxicillin, azithromycin,
      ciprofloxacin, chloramphenicol, meropenem, minocycline, oxytetracycline,
      sulfamethazine and vancomycin had highest removal by CAS or MBR systems with
      median removal efficiency (RE) > 70%, while trimethoprim and lincomycin were
      recalcitrant in the CAS system with median RE <50%. Similarly, the target ARB and
      ARGs were omnipresent in the raw influent samples with average concentrations as
      high as 2.6 * 106 CFU/mL and 2.0 * 107 gene copies/mL, respectively. The
      concentrations of ARB in secondary effluent of the CAS system declined relative
      to the raw influent (i.e. lower than raw influent by 2-3 orders of magnitude) and
      no ARB were detected in the MF permeate of the MBR system. For ARGs, their
      concentrations in secondary effluent/MF permeate ranged from below method
      quantification limit (<MQL) to 104 gene copies/mL. It is noteworthy that several
      ARGs, i.e. blaKPC, blaNDM, blaSHV, ermB, intI1, sul1 and tetO, were still found
      in the MF permeate of the MBR system at average concentrations up to 103
      copies/mL. In conclusion, MBR outperformed CAS in the elimination of ARB, ARGs
      and most target antibiotics.

PMID- 30193194
TI  - Hydrological benefits of filtering swales for metal removal.
AB  - This paper studies the hydraulic performance of two swales composed of filters
      for stormwater management (filtering swales) in a large-scale experimental study
      and compares them to the performance of a swale composed of traditional
      bioretention soil (bioswale). Using experimental data, dimensionless formulations
      are derived to reflect the influence of swale design parameters on hydraulic
      performance. The developed formulas can be used to design swales accounting for
      practical factors for decision makers such as local rainfall patterns, volume
      capture requirements, and drainage area. The experimental data show that while
      the bioswale is characterized by large overland flows, the tested filtering
      swales manage, in the majority of cases, the complete inflow volume without
      overland flow. The longitudinal slope of the swales does not affect the
      infiltration capacity of the filtering swales for the tested experimental
      boundary conditions, only the inflow rate and media water content are found to be
      statistically significant. As an example, filtering swales tested in this study
      captured 90% of the runoff generated by a 12.2 mm/h storm (approximately a 5-year
      return period 1-h duration storm event in the city of Trondheim) on a road 40
      times larger than the swale. This highlights the capacity of such swales for
      handling infrequent events.

PMID- 30193195
TI  - Combination of the CYP2C19 metabolizer and the GRACE risk score better predicts
      the long-term major adverse cardiac events in acute coronary syndrome undergoing
      percutaneous coronary intervention.
AB  - INTRODUCTION: Both Global Registry of Acute Coronary Events (GRACE) risk score
      and CYP2C19 metabolizer status can independently predict major adverse cardiac
      events (MACEs) in patients with acute coronary syndrome (ACS) undergoing
      percutaneous coronary intervention (PCI). We investigated whether their
      combination could better predict MACE occurrence in patients with ACS undergoing
      PCI. MATERIALS AND METHODS: This retrospective cohort study included 548
      consecutive patients with ACS undergoing PCI. A cumulative MACE curve was
      calculated using the Kaplan-Meier method. Multivariate Cox regression was used to
      identify MACE predictors. The predictive value of GRACE risk score alone and
      CYP2C19 metabolizer status was estimated by the area under the receiver operating
      characteristic curve (AUC), net reclassification improvement (NRI), and
      integrated discrimination improvement (IDI). RESULTS: In a median of 28.58
      months, 17 patients (3%) were lost to follow-up, and 62 (11.3%) experienced
      MACEs. Multivariate Cox regression analysis showed that both GRACE score and
      CYP2C19 metabolizer status were independent MACE predictors (hazard ratio 1.019,
      95% CI 1.011-1.027, p < 0.001; hazard ratio 2.383, 95% CI 1.601-3.547, p < 0.001,
      respectively). Kaplan-Meier analysis showed that CYP2C19 PM increased the MACE
      risk (log rank test = 10.848, p = 0.004). The GRACE score adjustment by CYP2C19
      metabolizer status enhanced the predictive value (AUC increased from 0.682 for
      GRACE score alone to 0.731 for GRACE score plus CYP2C19 metabolizer). This result
      was further verified by IDI and NRI. CONCLUSIONS: CYP2C19 metabolizer status and
      GRACE score are readily available predictive approaches for MACEs, and their
      combination derives a more accurate long-term MACE prediction in clopidogrel
      treated patients with ACS undergoing PCI.

PMID- 30193196
TI  - Comparative studies on amphotericin B nanosuspensions prepared by a high pressure
      homogenization method and an antisolvent precipitation method.
AB  - Amphotericin B (AmB) is a widely used polyene antifungal agent; however, its poor
      solubility limits its clinical application. In this study, AmB nanosuspensions
      were prepared by a high pressure homogenization method (AmB-HPH) and an
      antisolvent precipitation method (AmB-AP) to improve the drug solubility. To
      reveal the distinct influences of these two different preparation methods,
      systematic comparisons of particle size, crystalline state, wettability, in vitro
      dissolution and in vivo pharmacokinetics on the properties of AmB-HPH and AmB-AP
      were performed. The results indicated that AmB-AP was in an amorphous state,
      exhibiting higher saturation solubility and dissolution rate than those of AmB
      HPH in the crystalline state. However, the relative bioavailability of AmB-HPH
      was higher than that of AmB-AP in vivo, which was likely attributed to its better
      stability. In conclusion, both AmB-HPH and AmB-AP can enhance the solubility and
      bioavailability of AmB, but the stability of the nanosuspension prepared by the
      anti-solvent precipitation method should be carefully considered.

PMID- 30193197
TI  - Microfluidic fabrication of biocompatible poly(N-vinylcaprolactam)-based
      microcarriers for modulated thermo-responsive drug release.
AB  - Various thermo-responsive polymers have been developed for controlled drug
      delivery upon the local application of external heat. The development of thermo
      responsive polymers with high biocompatibility and tunable thermo-sensitivity is
      crucial for safe and efficient therapeutic application. In this study, thermo
      responsive drug carriers featuring tunable thermo-sensitivities were synthesized
      using biocompatible poly(N-vinyl caprolactam) (PVCL) and stop-flow lithography.
      The PVCL-based particles showed selective drug release depending on temperature,
      illustrating their feasibility for on-demand controlled drug delivery. The volume
      phase transition temperature (VPTT) of the PVCL-based particles can be adjusted
      to vary from room temperature to body temperature by controlling their monomer
      compositions. In addition, modulated drug release was achieved by constructing
      multicompartments of different thermo-sensitivities within the PVCL particles. To
      accomplish thermo-responsive anticancer therapy, doxorubicin (DOX) was
      encapsulated into the PVCL particles as an anticancer drug. The DOX-loaded PVCL
      particles exhibited both thermo-responsive drug release and anticancer activity.
      This study demonstrates that thermo-responsive PVCL particles are highly
      promising carriers for safe and targeted anticancer therapy.

PMID- 30193198
TI  - The effect of PLGA-based hydrogel scaffold for improving the drug maximum
      tolerated dose for in situ osteosarcoma treatment.
AB  - Although hydrogel-based therapeutic agents have shown great potential for
      localized cancer treatments, the maximum tolerated dose (MTD) of these methods
      remains uncertain. To confirm this, doxorubicin (DOX) loaded PLGA-PEG-PLGA
      hydrogel was employed to investigate the MTD of DOX for localized osteosarcoma
      treatment. This hydrogel showed good injectable and biodegradable properties in
      vivo. And the drug remaining time was also obviously prolonged in the tumor site.
      Different doses of DOX (5.0, 15, 30 mg/kg) with/without hydrogel were adopted to
      the treatment of tumor-bearing mice. Despite both localized administrations of
      5.0 mg/kg DOX showing no obvious systemic toxicity, this dose failed to control
      the persistent growth of tumors or prolong the survival time in comparison with
      the control groups. Localized administration of 30 mg/kg DOX showed a high
      efficacy for suppressing tumor growth, but exhibited obvious body weight losing
      at the same time. Correspondingly, the DOX-loaded hydrogel with the dose of 15
      mg/kg achieved significantly improved anti-tumor efficacy and prolonged mean
      survival time compared with both the free DOX (15 mg/kg) and other control
      groups. Furthermore, during the whole therapeutic process, the mice showed no
      obvious body weight loss, major organs damage or death in this group. The MTD of
      DOX-loaded agent based on the PLGA-PEG-PLGA hydrogel gave a 2-fold increase
      compared to the MTD of free DOX (7.5 mg/kg, intravenous injection) for the mouse
      without significant systemic toxicity.

PMID- 30193199
TI  - 13C-NMR-based metabolic fingerprinting of Citrus-type crude drugs.
AB  - Five Citrus-type crude drugs (40 samples) were classified using 13C-NMR spectra
      based metabolomics. The following eight metabolites were identified from the
      loading plots of multivariate analysis of the 13C-NMR spectra; naringin,
      neohesperidin, narirutin, synephrine, sucrose, alpha-glucose, beta-glucose, and
      limonene. 13C-NMR spectra-based metabolic fingerprinting is a promising strategy
      for classifying crude drugs.

PMID- 30193200
TI  - Screening and optimization of samarium-assisted complexation for the
      determination of norfloxacin, levofloxacin and lomefloxacin in their
      corresponding dosage forms employing spectrofluorimetry.
AB  - Multivariate strategy was applied for setting a fluorescent technique for the
      determination of three fluoroquinolones: norfloxacin (NOR), levofloxacin (LEV)
      and lomefloxacin (LOM) in their pure powder and dosage forms. Based on their
      known interaction with lanthanides, and augmented fluorescence intensity obtained
      by antenna effect at lambdaex/lambdaem = 314/553, 312/553 and 310/556 for NOR,
      LEV and LOM, respectively, the current research was scrutinized. Four continuous
      factors were selected for study in the screening step by means of Plackett-Burman
      Design, where temperature factor was excluded for being non-significant and the
      other factors as volume of metal ion solution, pH and reaction time were
      evaluated through Central Composite Design. 3-D surfaces demonstrations and 2-D
      contour plots designated the factors interactions followed by optimization plots,
      which defined the best blend for factors conjunction. pH factor was the chief
      motor force affecting the response as the number of coordinated ligands formed
      depends on the pH, whereas 1:2 complex is the main species at higher pH values
      followed by the volume of metal ion solution and ended by little effect of the
      reaction time. Model verification was monitored, which showed the model
      superiority for the three fluoroquinolones, where all target points tested were
      in good agreement with the predicted ones. The linear range for the tested drugs
      were found to be 0.090-1.280 MUg/mL for NOR, 0.068-1.448 MUg/mL for LEV and 0.077
      1.552 MUg/mL in case of LOM, thus approving the suitability of this method for
      Quality Control testing. Furthermore, applying these conditions to test the
      fluoroquinolones in their pharmaceuticals was done as well as intra and inter-day
      effects as to confirm the validity of this technique for routine analysis.
      Recovery % and RSD were found to be 99.958 +/- 0.797, 99.887 +/- 0.935 and
      100.427 +/- 0.698 for NOR, LEV and LOM respectively in their pure powder. While
      it was calculated to be 100.200 +/- 0.785, 100.530 +/- 0.396 and 100.620 +/-
      0.896 for NOR, LEV and LOM in their corresponding dosage forms. This excellent
      precision and accuracy obtained in results impulse it to be one of the most
      appropriate methods for further analysis.

PMID- 30193201
TI  - Metabolomic profile of insulin resistance in patients with multiple sclerosis is
      associated to the severity of the disease.
AB  - BACKGROUND: Dysglycemia and adiposity have been related to disability in patients
      with multiple sclerosis. The objective of this work was to determine the
      prevalence and characteristics of insulin resistance in patients with multiple
      sclerosis using the metabolomics Quantose score. METHODS: A total of 64 patients
      were accrued in the study. A blood sample was drawn to estimate the Quantose
      score, which is derived from fasting measurements of insulin, alpha
      hydroxybutyrate, linoleoyl-glycerophosphocholine, and oleate, three nonglucose
      metabolites shown to correlate with insulin-stimulated glucose disposal. RESULTS:
      Insulin resistance was documented in 33 out of 64 patients and it was found in
      association with the degree of disability and the time from diagnosis. Patients
      with the secondary progressive form of the disease showed the highest prevalence.
      CONCLUSION: Insulin resistance is frequent in patients with multiple sclerosis
      and might contribute to metabolic complications and general disability. Early
      markers of dysglycemia should be sought for in these patients to avoid additional
      deterioration of their quality of life.

PMID- 30193202
TI  - [INVOLVEMENT OF 5-HT1A RECEPTORS IN LONG-TERM INFLUENCE OF INFLAMMATORY PAIN AND
      STRESS IN EARLY AGE ON REACTIVITY OF NOCICEPTIVE SYSTEM].
AB  - Effects of inflammatory pain, short stress of maternal isolation and combination
      of these impacts in 1-day-old and repeatedly 2-day-old rat pups (neonatal period
      of development) on the indices of generalized pain and the inflammatory pain
      response were studied on the rats during the adulthood. To study the involvement
      of 5-HT1A receptors in the long-term impact of neonatal effects on pain
      sensitivity we used a chronic injection of 5-HT1A receptor agonist buspirone
      during the prepuberal period of rats which as newborn experienced similar impacts
      (control, injection of saline). It was found that in adult rats in which
      inflammatory pain and stress of maternal isolation during the first two days of
      life caused changes in pain sensitivity, buspirone normalized the indices of
      basic pain in the hot plate test and the pain response in the formalin test; the
      combination of these impacts did not cause any changes in the pain sensitivity,
      and the effect of buspirone did not appear. Thus, effects of buspirone found in
      this study suggest that 5-HT1A receptors are involved in the long-term influence
      of the studied adverse neonatal impacts on the reactivity of the nociceptive
      system.

PMID- 30193203
TI  - Pilot for novel context generalization paradigm.
AB  - BACKGROUND AND OBJECTIVES: Following an aversive experience, fears often
      generalize across contexts. Contextual fear generalization is modeled in a
      laboratory paradigm in which one context (CTX+) is paired with an aversive
      unconditional stimulus (US), while the other context (CTX-) is not. The current
      study sought to validate a novel paradigm assessing contextual fear
      generalization, and to determine the extent to which stress and anxiety symptoms
      enhanced contextual fear generalization. METHODS: Fifty-nine participants were
      randomized to a stress induction or control arithmetic test, followed by a
      differential context fear conditioning paradigm. One to three days later,
      participants completed a generalization gradient test with CTX+, CTX, and four
      generalization contexts. RESULTS: We found successful contextual fear
      conditioning on measures of US expectancy, self-report fear and valence, and
      startle reflex, and linear generalization across the contextual gradient on
      expectancies and self-report measures. Acute stress induction impaired learning
      of the US-CTX + association during context fear acquisition. Anxiety
      significantly predicted greater contextual fear generalization as measured by US
      expectancy. LIMITATIONS: Our study provides pilot data introducing a novel fear
      conditioning paradigm to assess contextual generalization of fear. There is a
      need for further replication to validate its utility. CONCLUSIONS: Findings
      suggest that individuals high in anxiety show greater contextual fear
      generalization as measured by US expectancy. Results are discussed in terms of
      potential mechanisms that contribute to pervasive anxiety.

PMID- 30193204
TI  - Indications and use of, and incidence of major bleeding with, antithrombotic
      agents in myelodysplastic syndrome.
AB  - Myelodysplastic syndrome (MDS) and antithrombotic medication both increase the
      risk of bleeding. We set out to analyze the prevalence of use, indications and
      bleeding risk of antithrombotic therapy in patients with MDS in a retrospective,
      single-center study including all patients with MDS with >20 * 109/L platelets.
      193 patients (59% male, median age 75 years) were included; 122 did not receive
      antithrombotic treatment, 51 received antiplatelet agents and 20 received
      anticoagulants. The cumulative incidence of major bleeding was higher in both the
      antiplatelet group (11.8% at 4 years, 95% confidence interval [95%CI]: 4.7-22.3%)
      and the anticoagulation group (21.2% at 4 years, 95%CI 6-42.5%) than in the
      control group (2.8% at 4 years 95%CI: 0.7-7.3%). The prevalence of use of
      antithrombotic medication in this cohort of patients with MDS was high and
      bleeding risk was increased in these patients.

PMID- 30193206
TI  - A case of a right accessory hepatic duct diagnosed during a Whipple procedure.
AB  - INTRODUCTION: Although anatomic variations of the bile tract are relatively
      common and can be present in about 28% of patients, existence of an accessory
      right hepatic duct that confluence on the common bile duct is quite rare.
      PRESENTATION OF CASE: We present a rare case of a caucasian 78-years-old patient,
      with accessory right hepatic duct which was diagnosed intraoperatively. The
      patient was submitted to Whipple procedure due to a mass in the head of pancreas.
      Intraoperatively, an accessory right hepatic duct that merged with the common
      bile duct was found, and a double bilio-intestinal anastomosis was performed.
      DISCUSSION: Definition of accessory hepatic duct, requires the existence of a
      main right hepatic duct, otherwise the definition of "accessory" is inconclusive.
      In our case the accessory right hepatic duct drained the posterior segments of
      the right hepatic lobe. CONCLUSION: A detailed mapping of the biliary tree is
      essential in patients that will undergo major interventions of the hepatobiliary
      system. Common and rare variations of the biliary tree should be known prior to
      any intervention to avoid intraoperative difficulties or complications.

PMID- 30193205
TI  - Rehospitalization to a child and adolescent psychiatry unit: Role of trauma and
      bullying.
AB  - OBJECTIVE: Psychiatric rehospitalizations results in a significant burden to
      patients, families, and health care systems. Understanding psychiatric
      rehospitalizations offers an opportunity to identify weaknesses in current
      systems of care. The objective of this study was to test the hypothesis that a
      history of trauma or ongoing bullying increases the risk of psychiatric
      rehospitalization. METHOD: Retrospective cohort study of 366 individual patients
      (71% female) admitted to a pediatric psychiatry unit between 1/1/2015 and
      12/31/2015. The primary outcome measure was rehospitalization to the same
      psychiatric hospital unit within one year of first discharge. Trauma was defined
      as having a history of Post-Traumatic Stress Disorder, Reactive Attachment
      Disorder, or a filed Suspected Abuse and Neglect of a Child report by the end of
      first hospitalization. Ongoing bullying was identified by medical record review.
      RESULTS: History of trauma (Odds Ratio (OR) = 3.2, 95% Confidence Interval (CI) =
      1.8-5.6, p < 0.0001) and ongoing bullying (OR = 2.2, CI = 1.2-3.9, p = 0.009)
      were significantly associated with increased rates of rehospitalizations. We
      controlled for the following covariates: Patient Health Questionnaire-9 Modified
      (PHQ-9M) score, gender, age, relative age, initial length of stay, disrupted
      family system, and sexual orientation/identity. CONCLUSION: History of trauma or
      ongoing bullying are important risk factors for pediatric psychiatric
      rehospitalization.

PMID- 30193207
TI  - Enhanced cortisol secretion in acute transient global amnesia.
AB  - INTRODUCTION: Stress-related transient inhibition of memory formation in the
      hippocampus has been hypothesized as one of the underlying pathomechanisms of
      transient global amnesia (TGA). TGA episodes, during which patients cannot encode
      and recall new information (anterograde amnesia affecting episodic long-term
      memory), are frequently preceded by a psychologically or physically stressful
      event. METHODS: We measured salivary cortisol during acute TGA in 14 patients, as
      well as cortisol day-profiles and the effect of experimental exposure to stress
      (using the socially evaluated cold pressor test) on cortisol levels during the
      subacute phase. We assessed psychiatric comorbidity as well as depression, trait
      anxiety and chronic stress. These findings were compared with data of 20 healthy
      controls. FINDINGS: Nine patients reported a precipitating stressor and all 14
      developed typical hippocampal lesions on follow-up MRI. During TGA, salivary
      cortisol levels were more than 3-fold higher compared to time-matched day levels.
      While there was no difference in mean cortisol levels of the diurnal rhythm, we
      found a significant interaction between groups during experimental stress
      exposure (p = 0.049) with the TGA group revealing a higher cortisol increase. The
      TGA group reported higher levels of depressive symptomatology (CES-D) and higher
      scores of chronic stress (TICS) compared with the control group and there was a
      significant correlation between cortisol increase during TGA and the results of
      self-rating according to the CES-D (r = 0.615; p = 0.004), as well as to the STAI
      (r = 0.702; p = 0.001). CONCLUSION: Our findings of enhanced secretion of
      cortisol in acute TGA patients correlating with symptoms of depression and
      anxiety and a persisting hyperreactivity to experimental stress in the subacute
      phase support the hypothesis that stress might be significant for the
      pathogenesis of TGA.

PMID- 30193208
TI  - Rapid composting techniques in Indian context and utilization of black soldier
      fly for enhanced decomposition of biodegradable wastes - A comprehensive review.
AB  - In the present scenario, solid waste management (SWM) has become one of the main
      concerns for urban waste managers in the developing world. This article reviews
      the recent trends and technologies associated with the process of composting.
      Utilization of black soldier fly (BSF) larvae can be one of the rapid methods for
      treatment of biodegradable wastes. A detailed review of the literature indicated
      that more importance is to be given on the pre-processing of Municipal Solid
      Waste (MSW) which includes segregation of biodegradables, inerts, metals for
      preparing the requisite substrate for application of the suitable technology. In
      developing countries, major emphasis should be given on curtailing the
      environmental and health impacts caused due to improper management of MSW and for
      developing some innovative as well as economically feasible systems for proper
      handling of MSW. BSF can transform the biodegradable wastes into biofuels and
      byproducts at a minimal cost. The utilization of BSF for treating various organic
      waste (OW) has been thoroughly studied and discussed in detail. The salient
      observations on the factors affecting the growth of BSF larvae as well as
      comprehensive analysis of patents on breeding and utilization of BSF are also
      presented in this paper. The present review also assesses the potential of
      various rapid composting techniques and advocates about the planning and
      development of real-scale treatment systems by the researchers, environmental
      planners and policy makers to eradicate the problem of solid wastes.

PMID- 30193209
TI  - Managing household socio-hydrological risk in Mexico city: A game to communicate
      and validate computational modeling with stakeholders.
AB  - Residents of Mexico City experience major hydrological risks, including flooding
      events and insufficient potable water access for many households. A participatory
      modeling project, MEGADAPT, examines hydrological risk as co-constructed by both
      biophysical and social factors and aims to explore alternative scenarios of
      governance. Within the model, neighborhoods are represented as agents that take
      actions to reduce their sensitivity to exposure and risk. These risk management
      actions (to protect their households against flooding and scarcity) are based
      upon insights derived from focus group discussions within various neighborhoods.
      We developed a role-playing game based on the model's rules in order to validate
      the assumptions we made about residents' decision-making given that we had
      translated qualitative information from focus group sessions into a quantitative
      model algorithm. This enables us to qualitatively validate the perspective and
      experience of residents in an agent-based model mid-way through the modeling
      process. Within the context of described hydrological events and the causes of
      these events, residents took on the role of themselves in the game and were asked
      to make decisions about how to protect their households against scarcity and
      flooding. After the game, we facilitated a discussion with residents about
      whether or not the game was realistic and how it could be improved. The game
      helped to validate our assumptions, validate the model with community members,
      and reinforced our connection with the community. We then discuss the potential
      further development of the game as a learning and communication tool.

PMID- 30193210
TI  - Retention modes of manure-fecal coliforms in soil under saturated hydraulic
      condition.
AB  - Manures are important soil nutrient conditioners and source of several pathogenic
      bacteria that potentially contribute to groundwater and surface water pollution.
      The best management practices need a solid understanding of manure sources,
      concentrations, and strategies to limit the number of bacteria in natural soil
      environment. In this study, a series of soil column experiments were conducted to
      investigate how bacteria mobility can potentially be influenced by retention
      mechanisms while moving through undisturbed saturated soil. This was assessed by
      bacteria retention profiles and mobility indices including the maximum
      transported (Cmax-T) and retained (Cmax-R) concentrations, filtration coefficient
      (lambdaf) and the maximum depth of bacteria transport (Zmax). Three different
      soil samples (sandy, loamy and silty clay loam) were enriched with three types of
      manures (cow, sheep, and poultry), placed on top of three soil columns (16 cm
      diameter, 30 cm height) with an equivalent of 10 Mg ha-1 (dry basis) summing up
      to a total of 36 columns. Leaching was performed under saturated steady-state
      conditions (i.e., 1.62 cm min-1) for a duration of 4 pore volumes. After
      percolation, soil columns were sliced into six 5-cm interval layers and slices
      were characterized for retained bacteria. Results showed irregular exponential or
      quasi-exponential bacteria retention profiles for cow and sheep manures, whereas
      uniform-shaped profiles occurred for poultry manure. The latter variant also
      switched to exponential shape for the sandy soil at the highest and lowest Cmax-T
      and Cmax-R values due to higher pore water velocity. The lambdaf and the Zmax
      values were also found to be affected by soil texture and manure origin. The
      lambdaf was higher for poultry manure due to higher free-cell transport of
      bacteria most probably induced by higher amount of soluble mobile components.
      However, the greater amounts of transported wooden materials released from cow
      and sheep manures acted as harbors for bacteria. Accordingly, the filtration rate
      decreased and tailing effects for bacteria transport increased. The results also
      suggest that the practices and strategies for using manures could be optimized
      according to the respective transport behavior to manage the bacteria retention
      with respect to soil and manure types to reduce soil and water pollution.

PMID- 30193211
TI  - Feeding frequency influences process performance and microbial community
      composition in anaerobic digesters treating steam exploded food waste.
AB  - In anaerobic digestion, studies of feeding frequency have produced conflicting
      results. Hence, the effect of feeding frequency on process variables and
      microbial community structure was investigated by comparing a laboratory-scale
      digester fed steam exploded food waste 10 times daily vs. one fed an equivalent
      amount once daily. The Frequently Fed Digester (FFD) produced on average 20% more
      methane and had lower effluent concentrations of long-chain fatty acids. Greater
      daily fluctuations in acetate, pH and biogas production rate could explain the
      lower specific methane yield and beta-oxidation. Feeding frequency also
      influenced the microbial community whereby Tenericutes (42%) dominated in FFD but
      Firmicutes (31%) was most abundant in the Daily Fed Digester (DFD). Feeding
      frequency effects are therefore postulated to occur more often in digesters fed
      labile feedstocks at high organic loading rates.

PMID- 30193212
TI  - Characterization of additional zinc ions on the growth, biochemical composition
      and photosynthetic performance from Spirulina platensis.
AB  - In this study, the effect of various initial Zn2+ concentration additionally on
      microalgae growth and biochemical composition were investigated. The Spirulina
      platensis biomass of each concentration reached the maximum at the end of the
      cultivation. However, high levels could severely inhibit the growth of
      microalgae. Fluorescence activity occurred changes in response to heavy metal
      stress. Moreover, biochemical composition in Spirulina platensis altered under
      zinc stress, and the highest contents of phycocyanin (PC), Chlorophyll-a (Chl-a),
      Carotenoid and zinc accumulation were obtained. The proportion of saturated and
      polyunsaturated fatty acids increased constantly in response to Zn2+ exposure.
      Overall, this study indicated that the use of Spirulina platensis is a viable
      method for treating zinc containing wastewater and harvested microalgae can be
      processed into high-zinc products.

PMID- 30193213
TI  - Enhancement of CO2 transfer and microalgae growth by perforated inverted arc
      trough internals in a flat-plate photobioreactor.
AB  - Flat-plate photobioreactor (PBR) with perforated inverted arc trough (PIAT)
      internals was proposed to promote CO2 bio-fixation by microalgae. The PIAT
      internals can enhance CO2 transfer from gas to culture medium by prolonging CO2
      gas-liquid contact time and generate periodic aeration in the suspension upper
      side the PIAT providing suspension mixing. Experimental results showed gas-liquid
      contact time was prolonged from 0.448 s to 256 s and the CO2 partial pressure
      inside the PIAT internals was about 15.5 kPa during microalgae cultivation.
      Consequently, the dissolved CO2 concentration in the microalgae suspension of the
      proposed PBR was increased by 26.0% compared to that in the PBR without PIAT
      internals when 15% CO2 (v/v) was aerated at a rate of 15 mL min-1. The elevated
      CO2 transfer contributed to a 20.9% increment in biomass concentration (3.35 g L
      1) and a 26.2% increment in CO2 fixation rate (36.6 mg L-1 h-1).

PMID- 30193214
TI  - Development of novel 2,4-bispyridyl thiophene-based compounds as highly potent
      and selective Dyrk1A inhibitors. Part I: Benzamide and benzylamide derivatives.
AB  - The protein kinase Dyrk1A modulates several processes relevant to the development
      or progression of Alzheimer's disease (AD), e. g. through phosphorylation of tau
      protein, amyloid precursor protein (APP) as well as proteins involved in the
      regulation of alternative splicing of tau pre-mRNA. Therefore, Dyrk1A has been
      proposed as a potential target for the treatment of AD. However, the co
      inhibition of other closely related kinases of the same family of protein kinases
      (e.g. Dyrk1B and Dyrk2) or kinases from other families such as Clk1 limits the
      use of Dyrk1A inhibitors, as this may cause unpredictable side effects especially
      over long treatment periods. Herein, we describe the design and synthesis of a
      series of amide functionalized 2,4-bispyridyl thiophene compounds, of which the 4
      fluorobenzyl amide derivative (31b) displayed the highest potency against Dyrk1A
      and remarkable selectivity over closely related kinases (IC50: Dyrk1A = 14.3 nM;
      Dyrk1B = 383 nM, Clk1 > 2 MUM). This degree of selectivity over the frequently
      hit off-targets has rarely been achieved to date. Additionally, 31b inhibited
      Dyrk1A in intact cells with high efficacy (IC50 = 79 nM). Furthermore, 31b
      displayed a high metabolic stability in vitro with a half-life of 2 h.
      Altogether, the benzamide and benzylamide extension at the 2,4-bispyridyl
      thiophene core improved several key properties, giving access to compound
      suitable for future in vivo studies.

PMID- 30193215
TI  - Small molecule-induced degradation of the full length and V7 truncated variant
      forms of human androgen receptor.
AB  - The androgen receptor (AR) is a hormone-activated transcription factor that
      regulates the development and progression of prostate cancer (PCa) and represents
      one of the most well-established drug targets. Currently clinically approved
      small molecule inhibitors of AR, such as enzalutamide, are built upon a common
      chemical scaffold that interacts with the AR by the same mechanism of action.
      These inhibitors eventually fail due to the emergence of drug-resistance in the
      form of AR mutations and expression of truncated AR splice variants (e.g. AR-V7)
      that are constitutively active, signalling the progression of the castration
      resistant state of the disease. The urgent need therefore continues for novel
      classes of AR inhibitors that can overcome drug resistance, especially since AR
      signalling remains important even in late-stage advanced PCa. Previously, we
      identified a collection of 10-benzylidene-10H-anthracen-9-ones that effectively
      inhibit AR transcriptional activity, induce AR degradation and display some
      ability to block recruitment of hormones to the receptor. In the current work, we
      extended the analysis of the lead compounds, and used methods of both ligand- and
      structure-based drug design to develop a panel of novel 10-benzylidene-10H
      anthracen-9-one derivatives capable of suppressing transcriptional activity and
      protein expression levels of both full length- and AR-V7 truncated forms of human
      androgen receptor. Importantly, the developed compounds efficiently inhibited the
      growth of AR-V7 dependent prostate cancer cell-lines which are completely
      resistant to all current anti-androgens.

PMID- 30193216
TI  - Sulfonyl-containing phenyl-pyrrolyl pentane analogues: Novel non-secosteroidal
      vitamin D receptor modulators with favorable physicochemical properties,
      pharmacokinetic properties and anti-tumor activity.
AB  - Modulating the vitamin D receptor (VDR) is an effective way to treat for cancer.
      We previously reported a potent non-secosteroidal VDR modulator (sw-22) with
      modest anti-tumor activity, which could be due to its undesirable physicochemical
      and pharmacokinetic properties. In this study, we investigated the structure
      activity and structure-property relationships around the 2'-hydroxyl group of sw
      22 to improve the physicochemical properties, pharmacokinetic properties and anti
      tumor activity. Compounds 19a and 27b, the potent non-secosteroidal VDR
      modulators, were identified as the most effective molecules in inhibiting the
      proliferation of three cancer cell lines, particularly breast cancer cells, with
      a low IC50 via the distribution of cell cycle and induction of apoptosis by
      stimulating the expression of p21, p27 and Bax. Further investigation revealed
      that 19a and 27b possessed favorable rat microsomal metabolic stability (2.22 and
      2.3 times, respectively, more stable than sw-22), solubility (43.9 and 50.2
      times, respectively, more soluble than sw-22) and in vivo pharmacokinetic
      properties. In addition, 19a and 27b showed excellent in vivo anti-tumor activity
      without cause hypercalcemia, which is the main side effect of marketed VDR
      modulators. In summary, the favorable physicochemical properties, pharmacokinetic
      properties and anti-tumor activity of 19a and 27b highlight their potential
      therapeutic applications in cancer treatment.

PMID- 30193217
TI  - Design of PPAR-gamma agonist based on algal metabolites and the endogenous ligand
      15-deoxy-Delta12, 14-prostaglandin J2.
AB  - In a previous study, we synthesized endocyclic enone jasmonate derivatives that
      function as anti-inflammatory and PPAR-gamma-activating entities by using key
      functional moieties of anti-inflammatory algal metabolites. Herein, we designed
      additional derivatives containing an exocyclic enone moiety that resembles the
      key structure of the natural PPAR-gamma ligand, 15-deoxy-Delta12, 14
      prostaglandin J2 (15 d-PGJ2). The exocyclic enone moiety of 15 d-PGJ2 is
      essential for covalent bonding with the Cys285 residue in the PPAR-gamma ligand
      binding domain (LBD). In silico analysis of the designed compounds indicated that
      they may form hydrogen bonds with key amino acid residues in the PPAR-gamma LBD,
      and thus, secure a position in the bioactive cavity in a similar fashion as does
      rosiglitazone and 15 d-PGJ2. By a luciferase reporter assay on rat liver Ac2F
      cells, the synthesized compounds were evaluated for PPAR-gamma transcriptional
      activity. The differential PPAR-gamma transcriptional activities of the geometric
      and enantiomeric isomers of the selected analog were also evaluated; based on our
      results, the enantiopure compound (+)-(R,E)-6a1 was suggested as a potential PPAR
      gamma ligand.

PMID- 30193218
TI  - Breathing new life into West Nile virus therapeutics; discovery and study of
      zafirlukast as an NS2B-NS3 protease inhibitor.
AB  - The West Nile virus (WNV) has spread throughout the world causing neuroinvasive
      diseases with no treatments available. The viral NS2B-NS3 protease is essential
      for WNV survival and replication in host cells and is a promising drug target.
      Through an enzymatic screen of the National Institute of Health clinical compound
      library, we report the discovery of zafirlukast, an FDA approved treatment for
      asthma, as an inhibitor for the WNV NS2B-NS3 protease. Zafirlukast was determined
      to inhibit the protease through a mixed mode mechanism with an IC50 value of 32
      MUM. A structure activity relationship study of zafirlukast revealed the
      cyclopentyl carbamate and N-aryl sulfonamide as structural elements crucial for
      NS2B-NS3 protease inhibition. Replacing the cyclopentyl with a phenyl improved
      inhibition, resulting in an IC50 of 22 MUM. Experimental and computational
      docking analysis support the inhibition model of zafirlukast and analogs binding
      at an allosteric site on the NS3 protein, thereby disrupting the NS2B cofactor
      from binding, resulting in protease inhibition.

PMID- 30193219
TI  - Discovery of new 2, 5-disubstituted 1,3-selenazoles as selective human carbonic
      anhydrase IX inhibitors with potent anti-tumor activity.
AB  - A series of disubstituted selenazole derivatives was synthetized and evaluated as
      carbonic anhydrase (CA, EC 4.2.1.1) inhibitors against the human (h) isoforms hCA
      I, II, IV, VA, VB and IX, involved in a variety of diseases including glaucoma,
      retinitis pigmentosa, epilepsy, arthritis and tumors. The investigated compounds
      showed potent inhibition against the tumor-associated transmembrane hCA IX, with
      KIs in the subnanomolar - low nanomolar range, and were evaluated for their
      effects on cell viability against the human prostate (PC3) and breast (MDA-MB
      231) cancer cell lines, showing effective anti-tumor activity. These selenazoles
      are interesting leads for the development of new, isoform-selective CA IX
      inhibitors.

PMID- 30193220
TI  - Recent developments of quinolone-based derivatives and their activities against
      Escherichia coli.
AB  - Escherichia coli (E. coli) is the most common pathogen in both hospital and
      community settings, and is capable of causing infections that can lead to serious
      consequences. Quinolones, one of the most common antibiotics in clinical use, are
      effective weapons to treat E. coli infections. However, the resistance of E. coli
      to quinolones develops rapidly and spreads widely. Thus, it has become
      increasingly urgent to enhance the potency of quinolones against both drug
      susceptible and drug-resistant E. coli. This review aims to summarize the recent
      developments of quinolone derivatives with potential activity against E. coli,
      and to discuss the structure-activity relationship for further rationale design
      of this kind of derivatives.

PMID- 30193222
TI  - Atrazine hinders PMA-induced neutrophil extracellular traps in carp via the
      promotion of apoptosis and inhibition of ROS burst, autophagy and glycolysis.
AB  - Atrazine (ATR), a selective herbicide, is consistently used worldwide and has
      been confirmed to be harmful to the health of aquatic organisms. The release of
      neutrophil extracellular traps (NETs) is one of the newly discovered
      antimicrobial mechanisms. Although several immune functions have been analyzed
      under ATR exposure, the effect of ATR on NETs remains mainly unexplored. In the
      present study, we treated carp neutrophils using 5 MUg/ml ATR and 5 MUg/ml ATR
      combined with 100 nM rapamycin to elucidate the underlying mechanisms and to
      clarify the effect of ATR on phorbol myristate acetate (PMA)-induced NETs. The
      results of the morphological observation and quantitative analysis of
      extracellular DNA and myeloperoxidase (MPO) showed that NETs formation were
      significantly inhibited by ATR exposure. Moreover, we found that in the NETs
      process, ATR downregulated the expression of the anti-apoptosis gene B-cell
      lymphoma-2 (Bcl-2), increased the expression of the pro-apoptosis factors Bcl-2
      Associated X (BAX), cysteinyl aspartate specific proteinases (Caspase3, 9), and
      anti-autophagy factor mammalian target of rapamycin (mTOR), decreased the
      expression of autophagy-related protein light chain 3B (LC3B) and glucose
      transport proteins (GLUT1, 4), disturbed the activities of phosphofructokinase
      (PFK), pyruvate kinase (PKM), and hexokinase (HK) and limited reactive oxygen
      species (ROS) levels, indicating that the reduced NETs release was a consequence
      of increased apoptosis and diminished ROS burst, autophagy and down-regulated
      glycolysis under ATR treatment. Meanwhile, rapamycin restored the inhibited
      autophagy and glycolysis and thus resisted the ATR-suppressed NETs. The present
      study perfects the mechanism theory of ATR immunotoxicity to fish and has a
      certain value for human health risk assessment.

PMID- 30193221
TI  - Synthesis and biological evaluation of novel Jiyuan Oridonin A-1,2,3-triazole
      azole derivatives as antiproliferative agents.
AB  - As a continuation of our research on developing potent and potentially safe anti
      proliferative agents, two series of novel Jiyuan Oridonin A-1,2,3-triazole-azole
      hybrids were designed, synthesized and evaluated for their anti-proliferative
      activity against four selected cancer cell lines (MGC-803, MCF-7, PC-3, Eca-109).
      Some compounds with better growth inhibitory effects were chosen to carry out
      further studies in A549 and SMMC-7721. Most of the synthesized compounds
      exhibited moderate to good activity against all the cancer cell lines selected.
      Particularly, the most active agent 8b showed high potency against human cancer
      cells with IC50 ranging from 0.2 +/- 0.0 to 5.0 +/- 0.9 MUM. Cellular mechanism
      studies elucidated compound 8b arrests cell cycle at G1 phase and induce a strong
      apoptotic response in SMMC-7721 cells. Furthermore, 8b could inhibit the colony
      formation and migration via Wnt signaling pathway in SMMC-7721 cells. For all
      these reasons, compound 8b holds promising potential as anti-proliferative agent.

PMID- 30193223
TI  - Assessment of trace metals in five most-consumed vegetables in the US:
      Conventional vs. organic.
AB  - Metal concentrations (As, Cd, Pb, Cr, Ba, Co, Ni, Cu, and Zn) in conventional and
      organic produce were assessed, specifically, five most-consumed vegetables from
      the US including potato, lettuce, tomato, carrot and onion. They were from four
      representative supermarkets in a college town in Florida. All vegetables
      contained detectable metals, while As, Cd, Pb, Cr, and Ba are toxic metals, Co,
      Ni, Cu, and Zn are nutrients for humans. The mean concentrations of As, Cd, Pb,
      Cr and Ba in five vegetables were 7.86, 9.17, 12.1, 44.8 and 410 MUg/kg for
      organic produce, slightly lower than conventional produce at 7.29, 15.3, 17.9,
      46.3 and 423 MUg/kg. The mean concentrations of Co, Ni, Cu, and Zn in five
      vegetables were 3.86, 58.5, 632, and 2528 MUg/kg for organic produce, comparable
      to conventional produce at 5.94, 68.2, 577, and 2354 MUg/kg. For toxic metals,
      the order followed tomato < lettuce < onion < carrot < potato, with root
      vegetables being the highest. All metals in vegetables were lower than the
      allowable concentrations by FAO/WHO. Health risks associated with vegetable
      consumption based on daily intake and non-carcinogenic risk based on hazard
      quotient were lower than allowable limits. For the five most-consumed vegetables
      in the US, metal contents in conventional produce were slightly greater than
      organic produce, especially for Cd and Pb.

PMID- 30193224
TI  - Beyond the west: Chemosignaling of emotions transcends ethno-cultural boundaries.
AB  - Accumulating evidence has pointed to a human capacity to communicate emotions to
      others via sweat. So far, these studies have relied exclusively on Western
      Caucasian samples. Our aim was to test whether the chemosensory communication of
      emotions extended beyond ethno-cultural boundaries, from Western Caucasians (N =
      48) to East Asians (N = 48). To test this, we used well-validated materials and
      procedures, a double-blind design, a pre-registered analysis plan, and a
      combination of facial electromyography (EMG) and continuous flash suppression
      techniques to measure unconscious emotions. Our results show that East Asian (and
      Western Caucasian) female receivers exposed to the sweat (body odor) of fearful,
      happy, and neutral Western Caucasian male senders emulate these respective states
      based on body odors, outside of awareness. More specifically, East Asian (and
      Western Caucasian) receivers demonstrated significantly different patterns of
      facial muscle activity when being exposed to fear odor, happy odor, and neutral
      odor. Furthermore, fear odor decreased the suppression time of all faces on an
      interocular suppression task (IST), indicating subconscious vigilance, whereas
      happy odor increased the detection speed of happy faces. These combined findings
      suggest that the ability to perceive emotional signals from body odor may be a
      universal phenomenon.

PMID- 30193225
TI  - Psychotherapeutic treatment and HPA axis regulation in posttraumatic stress
      disorder: A systematic review and meta-analysis.
AB  - Posttraumatic stress disorder (PTSD) has been associated with dysregulation of
      the hypothalamic-pituitary- adrenal (HPA) axis. Research over the past years has
      investigated potential changes of these alterations in the context of
      psychotherapy. Yet, no systematic review has been conducted. To summarize the
      current state of research on psychotherapy and HPA hormones, namely cortisol,
      dehydroepiandrosterone and its sulfate form (DHEA(S)), we searched for studies
      investigating predictions or changes in hormones over treatment course within the
      databases PubMed, Scopus, Medline, PsychINFO, Pilots/ProQuest, and Web of
      Science, and in the grey literature up to May 2018. Controlled and uncontrolled
      trials investigating adult samples with a clinical status of PTSD were eligible
      for inclusion. Twelve studies (428 participants) were included. Study quality was
      overall sufficient. Hormone assessment designs differed considerably. Treatment
      efficacy on PTSD symptom reduction was mostly high, but predictions of pre
      treatment hormone concentrations on treatment efficacy were largely non
      significant. Changes from pre- to post-test in basal cortisol (g = -0.07, 95% CI
      = -0.36; 0.21) and in the cortisol awakening response (g = -0.07, 95% CI = -0.48;
      0.35) were also non-significant. Future studies require comparable designs and
      need to be sufficiently powered to be able to detect potential associations with
      HPA regulation.

PMID- 30193226
TI  - Composition dependence of penetration range and backscattering coefficient of
      electrons impinging on SixGe1-x and GaAsxN1-x semiconducting alloys.
AB  - The alloy composition dependence of penetration range and backscattering
      coefficient of electrons normally impinging on SixGe1-x and GaAsxN1-x
      semiconductor alloys targets for beam energies in the range 0.5-3.5 keV has been
      investigated. The electron penetration range is calculated using the Ashley's
      model. The electron backscattering coefficient is determined using both the
      Vicanek and Urbassek theory where the transport cross-sections are obtained more
      accurately via an improved approximation and Monte Carlo method in which the
      inelastic scattering processes are treated via Ashley's optical model. Our
      results regarding the electron backscattering coefficient for Si and Ge targets
      are found to be much higher than those of experiment when using the Vicanek and
      Urbassek theory. However, the use of Ashley's model via Monte Carlo method gives
      results that are in reasonably good accord with the experimental data reported in
      the literature in the low energy regime being considered here.

PMID- 30193227
TI  - 3D reconstruction of the spatial distribution of dislocation loops using an
      automated stereo-imaging approach.
AB  - We propose an automated stereoscopic imaging approach for reconstructing the 3D
      spatial distribution of small dislocation loops (DLs) from 2D TEM micrographs.
      This method is demonstrated for small DLs in tungsten, formed by low-dose ion
      implantation, that appear as circular spots in diffraction contrast TEM images.
      To extract the 3D position of specific DLs, their 2D position in multiple weak
      beam dark-field TEM micrographs, recorded at different tilt angles, is fitted.
      From this fit the geometric centre and size of each DL in each micrograph can be
      extracted. To identify each specific DL in all the 2D projections, an automated
      forward prediction approach is used. A system of linear equations can then be
      setup, linking the 3D position of each DL to its 2D position in each projection,
      and solved using least-squares fitting. This approach is initially tested on
      synthetic data. For low projected loop densities (<20  *  1015 m-2) only 3
      projections are required for perfect recovery of the defect microstructure. More
      projections are required when the projected number density increases or realistic
      errors are included. 3D reconstruction of experimental data from the low-dose
      self-ion implanted tungsten sample reveals a damage microstructure in good
      agreement with the depth-dependent damage profile predicted by SRIM. A comparison
      with weighed back-projection shows that the stereo-imaging-approach requires
      fewer projections, is less sensitive to the angular range spanned, and is more
      resilient to spurious variations in local contrast. It also allows a more
      straightforward retrieval of quantitative information such as size and position
      of each loop.

PMID- 30193228
TI  - Modeling, dynamics and phosphoinositide binding of the pleckstrin homology domain
      of two novel PLCs: eta1 and eta2.
AB  - PH domains mediate interactions involved in cell signaling, intracellular
      membrane transport regulation and cytoskeleton organization. Some PH domains bind
      phosphoinositides with different affinity and specificity. The two novel PLCeta
      (1 and 2) possess an N-terminal PH domain (PHeta1 and PHeta2 respectively) that
      has been implicated in membrane association and induction of PLC activity.
      Understanding of the structure and dynamics is crucial for future modulation of
      lipid-protein interactions in PHeta1, PHeta2 and other PH domains. Therefore, the
      three-dimensional structure of PHeta1 and PHeta2 was modeled using ITASSER and
      phosphoinositides (IP3 and IP4) were docked in the inferred binding site using
      HADDOCK server. Molecular Dynamics simulations of unliganded and phosphoinositide
      bound PHeta1 and PHeta2 were performed using AMBER14 to study the mechanism of
      interaction, and conformational dynamics in response to phosphoinositide binding.
      The binding affinity was predicted using Kdeep server. The models of PHeta1 and
      PHeta2 had a conserved structural core consisting of seven beta-strands and a C
      terminal alpha-helix as seen in other PH domains. Sequence/structure analysis
      showed that phosphoinositide ligands bind PHeta1 and PHeta2 at the canonical
      binding site. Phosphoinositide binding induced movement of positively charged
      side chains towards the ligand, changes in the secondary structure especially at
      the beta5-beta6 loop and allosteric changes at the interface of beta1-beta2 and
      beta5-beta6 loops. Dynamics studies showed that the size of the binding site and
      differential affinity for IP3/IP4 binding is coordinated by the number, length,
      flexibility, secondary structure and allosteric interactions of the loops
      surrounding the phosphoinositide binding site.

PMID- 30193229
TI  - Homology modelling of human divalent metal transporter (DMT): Molecular docking
      and dynamic simulations for duodenal iron transport.
AB  - Iron transport through the duodenum is regulated by carrier proteins, one of
      which is the ubiquitously distributed divalent metal transporter (DMT1) which is
      responsible for the uptake of iron across the apical surface of the duodenal
      enterocyte. The crystallographic structure of Staphylococcus capitis divalent
      metal ion transporter (ScaDMT1) was obtained and it was used as a template for
      the construction of a homology model of human divalent metal transporter (hDMT1).
      The binding site for hDMT1 was determined by using SiteMap as well as molecular
      docking studies on ScaDMT1. The differences in binding modes between ScaDMT1 and
      hDMT1 were noted for a set of 7 iron containing compounds, including ferrous
      sulphate. Diffusion of ferrous ion was observed during the course of molecular
      dynamic simulation which corresponded to the postulated mechanism of iron
      transport. Further, the dock scores correlated well with relative
      bioavailabilities of the iron compounds. The study confirmed the efficacy of the
      in silico model which could be used for future studies on the absorption of
      micronutrients.

PMID- 30193230
TI  - Contribution of dissolved N2O in total N2O emission from sewage treatment plant.
AB  - The characteristics of nitrous oxide, N2O, from a sewage treatment plant, which
      conducts nitrogen removal, and the river that receives its effluent water, were
      investigated by intensive daily surveys in summer and winter. N2O production in
      the sewage treatment plant was promoted in winter when nitrite accumulated in the
      reaction tank. The dissolved N2O concentration in the effluent water was also
      high in winter, which caused the dissolved N2O concentration to increase in the
      river downstream. In contrast, the N2O production inside the plant and the
      dissolved N2O emission through the effluent water, the dissolved N2O discharge,
      was controlled in summer when the nitrogen removal was more complete and there
      was no-nitrite accumulation. The dissolved N2O in the effluent water was rapidly
      lost after leaving the plant by as much as 26% in summer and 59% in winter.
      Additionally, the amount of the dissolved N2O discharge in winter was almost
      equal to that of the indirect N2O emission. When the nitrogen removal proceeded
      successfully, the amount of dissolved N2O discharge was small. In contrast, when
      the nitrogen removal was insufficient, the dissolved N2O discharge became an
      important N2O source.

PMID- 30193231
TI  - 2D-QSAR and 3D-QSAR simulations for the reaction rate constants of organic
      compounds in ozone-hydrogen peroxide oxidation.
AB  - Synergistic oxidation of ozone (O3) and hydrogen peroxide (H2O2) is an effective
      water treatment for the elimination of organic pollutants. In this study, 23
      organic compounds were conducted to study the reaction rate constants during O3
      H2O2 oxidation. Then, two- and three-dimensional quantitative structure-activity
      relationship (QSAR) models were established to investigate the factors
      influencing the reaction rate constants by using multiple linear regression
      method and comparative molecular similarity index analysis (CoMSIA) method,
      respectively. Both of the two models showed good performance on predicting the
      reaction rate constants, the associated statistical indices of 2D-QSAR and 3D
      QSAR models were R2 = 0.898 and 0.952, q2 = 0.841 and 0.951, Qext2 = 0.968 and
      0.970, respectively. But varied in the influence factors, as for the 2D-QSAR
      model, three quantum chemical parameters, included dipole moment, the largest
      change of charge in each atom during the nucleophilic attack, the maximum
      positive partial charge on a hydrogen atom linked with a carbon atom affected the
      reaction rate. While in the 3D-QSAR model, the electrostatic field played the
      most important role in evaluating the reaction rate with the contribution of
      35.8%, followed by hydrogen bond acceptor and hydrophobic fields with the
      contribution of 24.9% and 23.2%, respectively. These two models provided
      predictive tools to study the influencing factors for the degradation of organics
      and might potentially be applied for estimating the removal properties of unknown
      organics in O3-H2O2 oxidation process.

PMID- 30193233
TI  - Surfactant-facilitated dechlorination of 2,2',5,5'-tetrachlorinated biphenyl
      using zero-valent iron in soil/sediment solution: Integrated effects of plausible
      factors.
AB  - Surfactants are used to assist the zero-valent iron-mediated reductive
      dechlorination (ZVI-RD) of hydrophobic organic contaminants (HOCs). Although the
      effect of surfactants has been investigated in single-factor systems, the
      relationships between the surfactant and the matrix properties during RD are not
      well understood. Thus, an orthogonal experiment and post-experiment
      characterization of ZVI were conducted in the present study to estimate the
      integrated effects of plausible factors. The results showed that the introduction
      of surfactants significantly influenced the reduction of 2,2',5,5'
      tetrachlorinated biphenyl (PCB-52) by altering the contact between ZVI and PCB
      52. An anionic surfactant was able to alleviate the adverse impact of high
      amounts of non-ionic surfactants and humic acid (used as representative soil
      organic matter) by changing their sorption behaviors, which were also influenced
      by the initial pH value. However, the reduction of ZVI by humic acid decreased
      the electron transfer efficiency of ZVI, and also reduced the contact between ZVI
      and PCB-52 by generating FeCO3. These results suggest that the rate-limiting
      process for the ZVI-RD of HOCs in the soil/sediment solution is the contact
      between ZVI and HOCs, which can be improved by the addition of surfactants at
      concentrations corresponding to the maximum adsorption capacity of HOCs on the
      ZVI surface.

PMID- 30193232
TI  - Response of the reactor performance and microbial community to a shift of ISDD
      process from micro-aerobic to anoxic condition.
AB  - Micro-aerobic condition has proven to be effective in enhancing sulfide oxidation
      to elemental sulfur (S0) during integrated simultaneous desulfurization and
      denitrification process (ISDD). In this study we investigated and compared the
      performance and microbial community of ISDD process operating under initially
      anoxic, then micro-aerobic and finally switch back to anoxic condition. For all
      the three tested scenarios, comparable bioreactor performance in terms of sulfate
      (95.0 +/- 4.4%, 90.6 +/- 3.8%, 89.8 +/- 3.5%) and nitrate (~100%) removal was
      achieved. However, a shift of ISDD bioreactor from micro-aerobic to anoxic
      environment clearly increased the S0 production (30.6%), relative to that at
      initial anoxic condition (14.2%). Further anoxic bioreactor operation with
      different influent nitrate concentrations also obtained satisfactory performance
      particularly in terms of S0 production. Microbial community analysis results
      showed that functional microorganisms selectively enriched at micro-aerobic
      condition, particularly sulfide-oxidizing bacteria (SOB), could also function
      well and enhance S0 production when bioreactor switching from micro-aerobic to
      anoxic environment. We proposed that micro-aerobic strategy could function as a
      bio-selector and provide a new idea in functional microorganisms selectively
      enrichment for wastewater treatment.

PMID- 30193234
TI  - Degradation of diclofenac by H2O2 activated with pre-magnetization Fe0:
      Influencing factors and degradation pathways.
AB  - Diclofenac sodium (DCF) is frequently detected as a non-steroidal pharmaceutical
      in the aquatic environment. In this study, the degradation of DCF in two
      heterogeneous systems, pre-magnetization Fe0/H2O2 (Pre-Fe0/H2O2) and Fe0/H2O2
      system, was comparably studied. Our findings proved that Pre-Fe0 could
      significantly improve the degradation and dechlorination of DCF due to the change
      of Fe0 characteristics after pre-magnetization. Compared with Fe0/H2O2 process,
      Pre-Fe0/H2O2 process has 2.1-7.0 times higher rate constant for DCF degradation
      at different H2O2 dosages (0.25-2.0 mM), initial pH (3.0-6.0) and Fe0 dosages
      (0.25-1.5 mM). The characterizations by X-ray Photoelectron Spectroscopy and
      Electron Paramagnetic Resonance confirmed that the enhancement attributed to the
      increase of Fe0 corrosion and fast generation of OH. In addition, preliminary
      degradation mechanism was elucidated by major products identification using UPLC
      MS, through which the degradation intermediates, such as 4-hydroxy-diclofenac or
      5-hydroxydiclofenac, 2,6-dichloroaniline, phenylacetic acid, 1,3-dichlorobenzene
      and 2-aminophenylacetic acid were identified. Hydroxylation, decarboxylation, CN
      bond cleavage and ring-opening involving the attack of OH or other substances,
      were the main degradation mechanism. Therefore, Pre-Fe0/H2O2 process, which does
      not need extra energy and costly reagents, is an efficient and environmental
      friendly process to degrade DCF.

PMID- 30193235
TI  - Ambient air pollution, H19/DMR methylation in cord blood and newborn size: A
      pilot study in Zhengzhou City, China.
AB  - Prenatal exposure to air pollutants is believed to be associated with adverse
      birth outcomes. However, the potential mechanisms, especially the epigenetic
      modified effects, still remain unclear. This study was designed to explore the
      association of air pollution, H19/DMR methylation levels, and birth weight and
      length. A total of 527 mother-infant pairs were recruited from Houzhai Center
      Hospital, Zhengzhou. Air pollution data during the study period was collected.
      The methylation at H19 promoter region and H19 DMR in maternal and cord bloods
      were determined using real-time PCR analysis. Ridge regression was used to
      analyze the association of air pollutants exposure during gestation with H19/DMR
      methylation and birth weight and length respectively. Results showed that
      prenatal exposure to NO2 was associated with higher H19 methylation in cord
      blood. Whereas SO2 and PM10 exposure were associated with lower H19 and H19 DMR
      methylation respectively. After stratification by pregnancy trimesters, the
      association of H19 methylation in cord blood with PM10 exposure also was found.
      Furthermore, prenatal exposures to air pollutants also were associated with birth
      weight and length. Specifically, with the increase of maternal SO2 exposure
      during the entire pregnancy, birth weight and length significantly decreased.
      While birth weight and birth length were significantly increased with NO2
      exposure. The stratified analysis also found the associations between PM10
      exposure and birth sizes in different trimesters. In conclusion, the gene
      methylation level in cord blood might be associated with prenatal environmental
      exposures. Birth weight and length were associated with both prenatal
      environmental exposures and genetic factors.

PMID- 30193236
TI  - Are clinical instructors preventing or provoking adverse events involving
      students: A contemporary issue.

PMID- 30193237
TI  - Development and evaluation of sexual assault training for emergency department
      staff in Ontario, Canada.
AB  - OBJECTIVE: The purpose of this evaluation was to assess the efficacy of a
      training in improving competence to address sexual assault among Emergency
      Department (ED) staff, as well as to compare in-person and online training
      modalities. METHODS: A total of 1564 staff from 76 EDs in acute care hospitals
      across Ontario participated in either on-site (n = 828 staff) or online (n = 736
      staff) training sessions, of whom 1366 (87%) completed both a pre- and post
      training questionnaire. Mean pre- and post-training scores measuring perceived
      competence in responding to victims/survivors of sexual assault were compared
      using paired t-tests. The mean gain score for in-person and online training was
      then compared using the Mann-Whitney U test. Finally, in-person and online
      participants' ratings of the training content and delivery were compared using
      the Mann-Whitney U test. RESULTS: There were significant improvements for all 16
      self-reported measures of competence following training. The mean gain in
      knowledge and skills was higher for in-person training participants. Participants
      in the in-person modality more strongly agreed that the information they learned
      would help in providing care for sexual assault victims/survivors, and were more
      satisfied with the training overall. However, these participants less strongly
      agreed that there was an appropriate amount of time allotted for the scope of
      material presented. CONCLUSIONS: Overall, the training led to immediate
      improvements in ED staff perceived understanding and ability to address the needs
      of victims/survivors of sexual assault, with particular advantages to the in
      person training.

PMID- 30193238
TI  - Ratios and distances of pull-up peaks observed in GlobalFiler kit data.
AB  - Short tandem repeat (STR) analysis is widely used for forensic examinations with
      a capillary electrophoresis instrument such as the 3500xL Genetic Analyzer. This
      instrument adapts multi-locus STR kits to examine up to 27 loci using a 6
      fluorescent dye system and corrects the spectral overlap between each dye.
      However, inaccurate spectral correction can cause pull-up peaks. Here, we
      examined the pull-up peaks observed in GlobalFiler kit data in terms of their
      peak height ratios and distances from their parent allele peaks when using the
      3500xL and the 3130xl Genetic Analyzers. With the 3500xL, 546 pull-up peaks were
      observed, and their pull-up ratios averaged 1.03 +/- 0.32% (range 0.260-2.80%).
      Of the 546 pull-up peaks, 534 peaks (97.8%) were within +/-1 bp from their parent
      allele peaks. Overall, the pull-up peaks toward adjacent shorter wavelength
      channels (e.g., from yellow to green) tended to be observed in the left side
      (shorter bp) of the corresponding parent allele peaks, and the opposite side
      tendency was observed for those pull-up peaks toward adjacent longer wavelength
      channels. These tendencies were also observed in the GlobalFiler data generated
      with the 3130xl and in the data obtained by injecting a J6 matrix standard with
      LIZ 500 or 600 v2 size standard into the 3500xL and 3130xl. Inspection of raw
      data revealed that the shift of pull-up peaks from their parent allele peaks was
      derived from sigmoid, pull-down, or slightly shifted pull-up shapes. Based on the
      obtained data, we propose a standard for assessment of questionable pull-up
      peaks.

PMID- 30193241
TI  - Missing Author Initial in Byline.

PMID- 30193243
TI  - Weeping Higan Cherry Tree, Central Park, New York City.

PMID- 30193244
TI  - Donut Falls, Wasatch National Forest, Utah.

PMID- 30193245
TI  - Opioid Death Rate Acceleration in Jurisdictions Legalizing Marijuana Use.

PMID- 30193240
TI  - Hyperprogressive Disease in Patients With Advanced Non-Small Cell Lung Cancer
      Treated With PD-1/PD-L1 Inhibitors or With Single-Agent Chemotherapy.
AB  - Importance: Hyperprogressive disease (HPD) is a new pattern of progression
      recently described in patients with cancer treated with programmed cell death 1
      (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors. The rate and
      outcome of HPD in advanced non-small cell lung cancer (NSCLC) are unknown.
      Objectives: To investigate whether HPD is observed in patients with advanced
      NSCLC treated with PD-1/PD-L1 inhibitors compared with single-agent chemotherapy
      and whether there is an association between treatment and HPD. Design, Setting,
      and Participants: In this multicenter retrospective study that included patients
      treated between August 4, 2011, and April 5, 2017, the setting was pretreated
      patients with advanced NSCLC who received PD-1/PD-L1 inhibitors (8 institutions)
      or single-agent chemotherapy (4 institutions) in France. Measurable disease
      defined by Response Evaluation Criteria in Solid Tumors (RECIST version 1.1) on
      at least 2 computed tomographic scans before treatment and 1 computed tomographic
      scan during treatment was required. Interventions: The tumor growth rate (TGR)
      before and during treatment and variation per month (DeltaTGR) were calculated.
      Hyperprogressive disease was defined as disease progression at the first
      evaluation with DeltaTGR exceeding 50%. Main Outcomes and Measures: The primary
      end point was assessment of the HPD rate in patients treated with IO or
      chemotherapy. Results: Among 406 eligible patients treated with PD-1/PD-L1
      inhibitors (63.8% male), 46.3% (n = 188) were 65 years or older, 72.4% (n = 294)
      had nonsquamous histology, and 92.9% (n = 377) received a PD-1 inhibitor as
      monotherapy in second-line therapy or later. The median follow-up was 12.1 months
      (95% CI, 10.1-13.8 months), and the median overall survival (OS) was 13.4 months
      (95% CI, 10.2-17.0 months). Fifty-six patients (13.8%) were classified as having
      HPD. Pseudoprogression was observed in 4.7% (n = 19) of the population.
      Hyperprogressive disease was significantly associated with more than 2 metastatic
      sites before PD-1/PD-L1 inhibitors compared with non-HPD (62.5% [35 of 56] vs
      42.6% [149 of 350]; P = .006). Patients experiencing HPD within the first 6 weeks
      of PD-1/PD-L1 inhibitor treatment had significantly lower OS compared with
      patients with progressive disease (median OS, 3.4 months [95% CI, 2.8-7.5 months]
      vs 6.2 months [95% CI, 5.3-7.9 months]; hazard ratio, 2.18 [95% CI, 1.29-3.69]; P
      = .003). Among 59 eligible patients treated with chemotherapy, 3 (5.1%) were
      classified as having HPD. Conclusions and Relevance: Our study suggests that HPD
      is more common with PD-1/PD-L1 inhibitors compared with chemotherapy in
      pretreated patients with NSCLC and is also associated with high metastatic burden
      and poor prognosis in patients treated with PD-1/PD-L1 inhibitors. Additional
      studies are needed to determine the molecular mechanisms involved in HPD.

PMID- 30193239
TI  - Association Between Physician Burnout and Patient Safety, Professionalism, and
      Patient Satisfaction: A Systematic Review and Meta-analysis.
AB  - Importance: Physician burnout has taken the form of an epidemic that may affect
      core domains of health care delivery, including patient safety, quality of care,
      and patient satisfaction. However, this evidence has not been systematically
      quantified. Objective: To examine whether physician burnout is associated with an
      increased risk of patient safety incidents, suboptimal care outcomes due to low
      professionalism, and lower patient satisfaction. Data Sources: MEDLINE, EMBASE,
      PsycInfo, and CINAHL databases were searched until October 22, 2017, using
      combinations of the key terms physicians, burnout, and patient care. Detailed
      standardized searches with no language restriction were undertaken. The reference
      lists of eligible studies and other relevant systematic reviews were hand
      searched. Study Selection: Quantitative observational studies. Data Extraction
      and Synthesis: Two independent reviewers were involved. The main meta-analysis
      was followed by subgroup and sensitivity analyses. All analyses were performed
      using random-effects models. Formal tests for heterogeneity (I2) and publication
      bias were performed. Main Outcomes and Measures: The core outcomes were the
      quantitative associations between burnout and patient safety, professionalism,
      and patient satisfaction reported as odds ratios (ORs) with their 95% CIs.
      Results: Of the 5234 records identified, 47 studies on 42 473 physicians (25 059
      [59.0%] men; median age, 38 years [range, 27-53 years]) were included in the meta
      analysis. Physician burnout was associated with an increased risk of patient
      safety incidents (OR, 1.96; 95% CI, 1.59-2.40), poorer quality of care due to low
      professionalism (OR, 2.31; 95% CI, 1.87-2.85), and reduced patient satisfaction
      (OR, 2.28; 95% CI, 1.42-3.68). The heterogeneity was high and the study quality
      was low to moderate. The links between burnout and low professionalism were
      larger in residents and early-career (<=5 years post residency) physicians
      compared with middle- and late-career physicians (Cohen Q = 7.27; P = .003). The
      reporting method of patient safety incidents and professionalism (physician
      reported vs system-recorded) significantly influenced the main results (Cohen Q =
      8.14; P = .007). Conclusions and Relevance: This meta-analysis provides evidence
      that physician burnout may jeopardize patient care; reversal of this risk has to
      be viewed as a fundamental health care policy goal across the globe. Health care
      organizations are encouraged to invest in efforts to improve physician wellness,
      particularly for early-career physicians. The methods of recording patient care
      quality and safety outcomes require improvements to concisely capture the outcome
      of burnout on the performance of health care organizations.

PMID- 30193246
TI  - Toenail Examination Reveals Unmet Care Needs.

PMID- 30193247
TI  - Opioid Death Rate Acceleration in Jurisdictions Legalizing Marijuana Use-Reply.

PMID- 30193248
TI  - Opioid Death Rate Acceleration in Jurisdictions Legalizing Marijuana Use-Reply.

PMID- 30193249
TI  - Toenail Examination Reveals Unmet Care Needs-Reply.

PMID- 30193251
TI  - Complementary and Alternative Medicine Therapies for Psoriasis: A Systematic
      Review.
AB  - Importance: Up to 51% of patients with psoriasis report the use of complementary
      and alternative medicine (CAM) in their treatment regimen, although it is unclear
      which CAM therapies are effective for treatment of psoriasis. Objective: This
      review compiles the evidence on the efficacy of the most studied CAM modalities
      for treatment of patients with plaque psoriasis and discusses those therapies
      with the most robust available evidence. Evidence Review: PubMed, Embase, and
      ClinicalTrials.gov searches (1950-2017) were used to identify all documented CAM
      psoriasis interventions in the literature. The criteria were further refined to
      focus on those treatments identified in the first step that had the highest level
      of evidence for plaque psoriasis with more than 1 randomized clinical trial
      supporting their use. This excluded therapies lacking randomized clinical trial
      (RCT) data or showing consistent inefficacy. Findings: Primary CAM therapy
      searches identified 457 articles, of which 107 articles were retrieved for closer
      examination. Of those articles, 54 were excluded because the CAM therapy did not
      have more than 1 RCT on the subject or showed consistent lack of efficacy. An
      additional 7 articles were found using references of the included studies,
      resulting in a total of 44 RCTs (17 double-blind, 13 single-blind, and 14
      nonblind), 10 uncontrolled trials, 2 open-label nonrandomized controlled trials,
      1 prospective controlled trial, and 3 meta-analyses. Compared with placebo,
      application of topical indigo naturalis, studied in 5 RCTs with 215 participants,
      showed significant improvements in the treatment of psoriasis. Treatment with
      curcumin, examined in 3 RCTs (with a total of 118 participants), 1 nonrandomized
      controlled study, and 1 uncontrolled study, conferred statistically and
      clinically significant improvements in psoriasis plaques. Fish oil treatment was
      evaluated in 20 studies (12 RCTs, 1 open-label nonrandomized controlled trial,
      and 7 uncontrolled studies); most of the RCTs showed no significant improvement
      in psoriasis, whereas most of the uncontrolled studies showed benefit when fish
      oil was used daily. Meditation and guided imagery therapies were studied in 3
      single-blind RCTs (with a total of 112 patients) and showed modest efficacy in
      treatment of psoriasis. One meta-analysis of 13 RCTs examined the association of
      acupuncture with improvement in psoriasis and showed significant improvement with
      acupuncture compared with placebo. Conclusions and Relevance: The CAM therapies
      with the most robust evidence of efficacy for treatment of psoriasis are indigo
      naturalis, curcumin, dietary modification, fish oil, meditation, and acupuncture.
      This review will aid practitioners in advising patients seeking unconventional
      approaches for treatment of psoriasis.

PMID- 30193252
TI  - Opioid Prescription Patterns After Rhinoplasty.

PMID- 30193254
TI  - Clinical Trials, End Points, and Statistics-Measuring and Comparing Cancer
      Treatments in Practice.

PMID- 30193253
TI  - Effect of Mobile Device-Supported Single-Patient Multi-crossover Trials on
      Treatment of Chronic Musculoskeletal Pain: A Randomized Clinical Trial.
AB  - Importance: Individually designed single-patient multi-crossover (n-of-1) trials
      can facilitate tailoring of treatments directed at various conditions, including
      chronic musculoskeletal pain (CMSP) but are potentially burdensome, which may
      limit uptake in research and practice. Objectives: To determine whether patients
      randomized to participate in an n-of-1 trial supported by a mobile health
      (mHealth) app would experience less pain and improved global health, adherence,
      satisfaction, and shared decision making compared with patients assigned to usual
      care. Design, Setting, and Participants: This randomized clinical trial compared
      participation in an individualized, mHealth-supported n-of-1 trial vs usual care.
      The participating 215 patients had CMSP for at least 6 weeks, had a smartphone or
      tablet with a data plan, were enrolled in northern California from July 2014
      through July 2016, and were followed for up to 1 year by 48 clinicians in
      academic, community, Veterans Affairs, and military settings. Interventions:
      Intervention patients met with their clinicians and used a desktop interface to
      select treatments and trial parameters for an n-of-1 trial comparing 2 pain
      management regimens. The mHealth app provided reminders to take designated
      treatments on assigned days and to upload responses to daily questions on pain
      and treatment-associated adverse effects. Control patients received care as
      usual. Main Outcomes and Measures: The primary outcome was change in the PROMIS
      (Patient-Reported Outcomes Measurement Information System) pain-related
      interference 8-item short-form scale (full scale range, 41-78) from baseline to 6
      months. Secondary outcomes included patient-reported pain intensity, overall
      health, analgesic adherence, trust in clinician, satisfaction with care,
      medication-related shared decision making, and, for the n-of-1 group only,
      participant engagement and experience. Results: Among 215 patients (108
      randomized to the n-of-1 intervention and 107 to control), 102 (47%) were women,
      and the mean (SD) age was 55.5 (11.1) years. At the 6-month follow-up, pain
      interference was reduced in both groups, though there was no difference between
      the intervention and control groups (-1.36 points; 95% CI, -2.91 to 0.19 points;
      P = .09). There were no advantages in secondary outcomes for intervention
      patients vs control patients except for higher medication-related shared decision
      making at 6 months (between-group difference, 11.9 points; 95% CI, 2.6-21.2
      points; P = .01). Among patients assigned to the n-of-1 group, 88% (n = 86)
      affirmed that the mHealth app could help people like them manage their pain.
      Conclusions and Relevance: In this population of patients with CMSP, mHealth
      supported n-of-1 trials were feasible and associated with a satisfactory user
      experience, but n-of-1 trial participation did not significantly improve pain
      interference at 6 months vs usual care. Trial Registration: ClinicalTrials.gov
      identifier: NCT02116621.

PMID- 30193255
TI  - Research Reveals Mechanism That May Drive Alcohol Use Disorder.

PMID- 30193256
TI  - Incorrect Medication Reported.

PMID- 30193257
TI  - Error in Figure.

PMID- 30193260
TI  - When Is Milk Really Milk?

PMID- 30193259
TI  - New Endometriosis Drug Approved.

PMID- 30193258
TI  - Medicare Bundled Payment Programs for Joint Replacement: Anatomy of a Successful
      Payment Reform.

PMID- 30193261
TI  - Magnetic Tracer System Identifies Sentinel Lymph Nodes.

PMID- 30193263
TI  - The Dietary Habits of American College Girls.

PMID- 30193264
TI  - Out-of-Pocket Costs for Infliximab and Its Biosimilar for Rheumatoid Arthritis
      Under Medicare Part D.

PMID- 30193265
TI  - Uptake of the Biologic Filgrastim and Its Biosimilar Product Among the Medicare
      Population.

PMID- 30193266
TI  - SMART in the Management of Patients With Persistent Asthma.

PMID- 30193267
TI  - Lowering the P Value Threshold.

PMID- 30193268
TI  - Lowering the P Value Threshold.

PMID- 30193269
TI  - Lowering the P Value Threshold.

PMID- 30193270
TI  - Lowering the P Value Threshold.

PMID- 30193271
TI  - Lowering the P Value Threshold.

PMID- 30193272
TI  - SMART in the Management of Patients With Persistent Asthma-Reply.

PMID- 30193274
TI  - Drugs for Tobacco Dependence.

PMID- 30193273
TI  - Lowering the P Value Threshold-Reply.

PMID- 30193275
TI  - Effect of Immediate vs Gradual Reduction in Nicotine Content of Cigarettes on
      Biomarkers of Smoke Exposure: A Randomized Clinical Trial.
AB  - Importance: The optimal temporal approach for reducing nicotine to minimally or
      nonaddictive levels in all cigarettes sold in the United States has not been
      determined. Objectives: To determine the effects of immediate vs gradual
      reduction in nicotine content to very low levels and as compared with usual
      nicotine level cigarettes on biomarkers of toxicant exposure. Design, Setting,
      and Participants: A double-blind, randomized, parallel-design study with 2 weeks
      of baseline smoking and 20 weeks of intervention was conducted at 10 US sites. A
      volunteer sample of daily smokers with no intention to quit within 30 days was
      recruited between July 2014 and September 2016, with the last follow-up completed
      in March 2017. Interventions: (1) Immediate reduction to 0.4 mg of nicotine per
      gram of tobacco cigarettes; (2) gradual reduction from 15.5 mg to 0.4 mg of
      nicotine per gram of tobacco cigarettes with 5 monthly dose changes; or (3)
      maintenance on 15.5 mg of nicotine per gram of tobacco cigarettes. Main Outcomes
      and Measures: Between-group differences in 3 co-primary biomarkers of smoke
      toxicant exposure: breath carbon monoxide (CO), urine 3-hydroxypropylmercapturic
      acid (3-HPMA, metabolite of acrolein), and urine phenanthrene tetraol (PheT,
      indicator of polycyclic aromatic hydrocarbons) calculated as area under the
      concentration-time curve over the 20 weeks of intervention. Results: Among 1250
      randomized participants (mean age, 45 years; 549 women [44%]; 958 [77%] completed
      the trial), significantly lower levels of exposure were observed in the immediate
      vs gradual reduction group for CO (mean difference, -4.06 parts per million [ppm]
      [95% CI, -4.89 to -3.23]; P < .0055), 3-HPMA (ratio of geometric means, 0.83 [95%
      CI, 0.77 to 0.88]; P < .0055), and PheT (ratio of geometric means, 0.88 [95% CI,
      0.83 to 0.93]; P < .0055). Significantly lower levels of exposure were observed
      in the immediate reduction vs control group for CO (mean difference, -3.38 [95%
      CI, -4.40 to -2.36]; P < .0055), 3-HPMA (ratio of geometric means, 0.81 [95% CI,
      0.75 to 0.88]; P < .0055), and PheT (ratio of geometric means, 0.86 [95% CI, 0.81
      to 0.92]; P < .0055). No significant differences were observed between the
      gradual reduction vs control groups for CO (mean difference, 0.68 [95% CI, -0.31
      to 1.67]; P = .18), 3-HPMA (ratio of geometric means, 0.98 [95% CI, 0.91 to
      1.06]; P = .64), and PheT (ratio of geometric means, 0.98 [95% CI, 0.92 to 1.04];
      P = .52). Conclusions and Relevance: Among smokers, immediate reduction of
      nicotine in cigarettes led to significantly greater decreases in biomarkers of
      smoke exposure across time compared with gradual reduction or a control group,
      with no significant differences between gradual reduction and control. Trial
      Registration: clinicaltrials.gov Identifier: NCT02139930.

PMID- 30193276
TI  - Association of Hospital Participation in a Medicare Bundled Payment Program With
      Volume and Case Mix of Lower Extremity Joint Replacement Episodes.
AB  - Importance: Medicare's Bundled Payments for Care Improvement (BPCI) initiative
      for lower extremity joint replacement (LEJR) surgery has been associated with a
      reduction in episode spending and stable-to-improved quality. However, BPCI may
      create unintended effects by prompting participating hospitals to increase the
      overall volume of episodes paid for by Medicare, which could potentially
      eliminate program-related savings or prompt them to shift case mix to lower-risk
      patients. Objective: To evaluate whether hospital BPCI participation for LEJR was
      associated with changes in overall volume and case mix. Design, Setting, and
      Participants: Observational study using Medicare claims data and a difference-in
      differences method to compare 131 markets (hospital referral regions) with at
      least 1 BPCI participant hospital (n = 322) and 175 markets with no participating
      hospitals (n = 1340), accounting for 580 043 Medicare beneficiaries treated
      before (January 2011-September 2013) and 462 161 after (October 2013-December
      2015) establishing the BPCI initiative. Hospital-level case-mix changes were
      assessed by comparing 265 participating hospitals with a 1:1 propensity-matched
      set of nonparticipating hospitals from non-BPCI markets. Exposures: Hospital BPCI
      participation. Main Outcomes and Measures: Changes in market-level LEJR volume in
      the before vs after BPCI periods and changes in hospital-level case mix based on
      demographic, socioeconomic, clinical, and utilization factors. Results: Among the
      1 717 243 Medicare beneficiaries who underwent LEJR (mean age, 75 years; 64%
      women; and 95% nonblack race/ethnicity), BPCI participation was not significantly
      associated with a change in overall market-level volume. The mean quarterly
      market volume in non-BPCI markets increased 3.8% from 3.8 episodes per 1000
      beneficiaries before BPCI to 3.9 episodes per 1000 beneficiaries after BPCI was
      launched. For BPCI markets, the mean quarterly market volume increased 4.4% from
      3.6 episodes per 1000 beneficiaries before BPCI to 3.8 episodes per 1000
      beneficiaries after BPCI was launched. The adjusted difference-in-differences
      estimate between the market types was 0.32% (95% CI, -0.06% to 0.69%; P = .10).
      Among 20 demographic, socioeconomic, clinical, and utilization factors, BPCI
      participation was associated with differential changes in hospital-level case mix
      for only 1 factor, prior skilled nursing facility use (adjusted difference-in
      differences estimate, -0.53%; 95% CI, -0.96% to -0.10%; P = .01) in BPCI vs non
      BPCI markets. Conclusions and Relevance: In this observational study of Medicare
      beneficiaries who underwent LEJR, hospital participation in Bundled Payments for
      Care Improvement was not associated with changes in market-level lower extremity
      joint replacement volume and largely was not associated with changes in hospital
      case mix. These findings may provide reassurance regarding 2 potential unintended
      effects associated with bundled payments for LEJR.

PMID- 30193278
TI  - Screening for Syphilis in Pregnant Women.

PMID- 30193277
TI  - Mandatory Medicare Bundled Payment Program for Lower Extremity Joint Replacement
      and Discharge to Institutional Postacute Care: Interim Analysis of the First Year
      of a 5-Year Randomized Trial.
AB  - Importance: Bundled payments are an increasingly common alternative payment model
      for Medicare, yet there is limited evidence regarding their effectiveness.
      Objective: To report interim outcomes from the first year of implementation of a
      bundled payment model for lower extremity joint replacement (LEJR). Design,
      Setting, and Participants: As part of a 5-year, mandatory-participation
      randomized trial by the Centers for Medicare & Medicaid Services, eligible
      metropolitan statistical areas (MSAs) were randomized to the Comprehensive Care
      for Joint Replacement (CJR) bundled payment model for LEJR episodes or to a
      control group. In the first performance year, hospitals received bonus payments
      if Medicare spending for LEJR episodes was below the target price and hospitals
      met quality standards. This interim analysis reports first-year data on LEJR
      episodes starting April 1, 2016, with data collection through December 31, 2016.
      Exposure: Randomization of MSAs into the CJR bundled payment model group (75
      assigned; 67 included) or to the control group without the CJR model (121
      assigned; 121 included). Instrumental variable analysis was used to evaluate the
      relationship between inclusion of MSAs in the CJR model and outcomes. Main
      Outcomes and Measures: The primary outcome was share of LEJR admissions
      discharged to institutional postacute care. Secondary outcomes included the
      number of days in institutional postacute care, discharges to other locations,
      Medicare spending during the episode (overall and for institutional postacute
      care), net Medicare spending during the episode, LEJR patient volume and patient
      case mix, and quality-of-care measures. Results: Among the 196 MSAs and 1633
      hospitals, 131 285 eligible LEJR procedures were performed during the study
      period (mean volume, 110 LEJR episodes per hospital) among 130 343 patients (mean
      age, 72.5 [SD, 0.91] years; 65% women; 90% white). The mean percentage of LEJR
      admissions discharged to institutional postacute care was 33.7% (SD, 11.2%) in
      the control group and was 2.9 percentage points lower (95% CI, -4.95 to -0.90
      percentage points) in the CJR group. Mean Medicare spending for institutional
      postacute care per LEJR episode was $3871 (SD, $1394) in the control group and
      was $307 lower (95% CI, -$587 to -$27) in the CJR group. Mean overall Medicare
      spending per LEJR episode was $22 872 (SD, $3619) in the control group and was
      $453 lower (95% CI, -$909 to $3) in the CJR group, a statistically nonsignificant
      difference. None of the other secondary outcomes differed significantly between
      groups. Conclusions and Relevance: In this interim analysis of the first year of
      the CJR bundled payment model for LEJR among Medicare beneficiaries, MSAs covered
      by CJR, compared with those that were not, had a significantly lower percentage
      of discharges to institutional postacute care but no significant difference in
      total Medicare spending per LEJR episode. Further evaluation is needed as the
      program is more fully implemented. Trial Registration: ClinicalTrials.gov
      Identifier: NCT03407885; American Economic Association Registry Identifier:
      AEARCTR-0002521.

PMID- 30193280
TI  - Good Documentation.

PMID- 30193282
TI  - Screening for Syphilis Infection in Pregnant Women: Updated Evidence Report and
      Systematic Review for the US Preventive Services Task Force.
AB  - Importance: The incidence of syphilis and congenital syphilis in the United
      States has increased after reaching historic lows in the early 2000s. Objective:
      To systematically review literature on the effectiveness and harms of screening
      for syphilis in pregnancy and the harms of penicillin treatment in pregnancy to
      inform the US Preventive Services Task Force. Data Sources: MEDLINE, PubMed, and
      the Cochrane Central Register of Controlled Trials for relevant English-language
      literature, published from January 1, 2008, to June 2, 2017. Ongoing surveillance
      was conducted through November 22, 2017. Study Selection: Studies conducted in
      countries categorized as "high" or "very high" on the Human Development Index
      that explicitly addressed 1 of 3 a priori-defined key questions. Data Extraction
      and Synthesis: Independent critical appraisal and data abstraction by 2
      reviewers. Data from included studies were narratively synthesized without
      pooling data. Main Outcomes and Measures: Incidence of congenital syphilis; any
      harms of screening or penicillin treatment in pregnancy. Results: Seven studies
      in 8 publications were included. One observational study evaluated the
      implementation of syphilis screening in pregnancy in 2 441 237 women in China.
      From 2002 to 2012, screening for syphilis in all pregnant women increased from
      89.8% to 97.2%, and the incidence of congenital syphilis decreased from 109.3 to
      9.4 cases per 100 000 live births. Five studies (n = 21 795) evaluated the false
      positive findings of treponemal tests and 1 study (n = 318) evaluated the false
      negative findings of nontreponemal tests. These studies found that false
      positives with treponemal-specific enzyme or chemiluminescent immunoassays were
      common (46.5%-88.2%), therefore warranting reflexive (automatic confirmatory)
      testing for all positive test findings. One study (n = 318) found no false
      negatives with treponemal tests, and 1 study (n = 139) demonstrated the prozone
      phenomenon (false-negative response from high antibody titer) with rapid plasma
      reagin screening using undiluted samples (2.9%). No studies were identified for
      harms of penicillin in pregnancy. Conclusions and Relevance: Screening for
      syphilis infection in pregnant women is associated with reduced incidence of
      congenital syphilis, and available evidence supports the need for reflexive
      testing for positive test results.

PMID- 30193285
TI  - Omitted Conflict of Interest Disclosures.

PMID- 30193283
TI  - Screening for Syphilis Infection in Pregnant Women: US Preventive Services Task
      Force Reaffirmation Recommendation Statement.
AB  - Importance: Untreated syphilis infection in pregnant women can be transmitted to
      the fetus (congenital syphilis) at any time during pregnancy or at birth.
      Congenital syphilis is associated with stillbirth, neonatal death, and
      significant morbidity in infants (eg, bone deformities and neurologic
      impairment). After a steady decline from 2008 to 2012, cases of congenital
      syphilis markedly increased from 2012 to 2106, from 8.4 to 15.7 cases per 100 000
      live births (an increase of 87%). At the same time, national rates of syphilis
      increased among women of reproductive age. Objective: To update the US Preventive
      Services Task Force (USPSTF) 2009 recommendation on screening for syphilis
      infection in pregnant women. Evidence Review: The USPSTF commissioned a
      reaffirmation evidence update to identify new and substantial evidence sufficient
      enough to change its prior recommendation. Given the established benefits and
      practice of screening for syphilis in pregnant women, the USPSTF targeted its
      evidence review on the direct benefits of screening on the prevention of
      congenital syphilis morbidity and mortality and the harms of screening for and
      treatment of syphilis infection in pregnant women. Findings: Using a
      reaffirmation process, the USPSTF found that accurate screening algorithms are
      available to identify syphilis infection. Effective treatment with antibiotics
      can prevent congenital syphilis and significantly decrease adverse pregnancy
      outcomes, with small associated harms, providing an overall substantial health
      benefit. Therefore, the USPSTF reaffirms its previous conclusion that there is
      convincing evidence that screening for syphilis infection in pregnant women
      provides substantial benefit. Conclusions and Recommendation: The USPSTF
      recommends early screening for syphilis infection in all pregnant women. (A
      recommendation).

PMID- 30193286
TI  - Optimizing Prehospital Triage for Patients With Stroke Involving Large Vessel
      Occlusion: The Road Less Traveled.

PMID- 30193284
TI  - Centers for Disease Control and Prevention Guideline on the Diagnosis and
      Management of Mild Traumatic Brain Injury Among Children.
AB  - Importance: Mild traumatic brain injury (mTBI), or concussion, in children is a
      rapidly growing public health concern because epidemiologic data indicate a
      marked increase in the number of emergency department visits for mTBI over the
      past decade. However, no evidence-based clinical guidelines have been developed
      to date for diagnosing and managing pediatric mTBI in the United States.
      Objective: To provide a guideline based on a previous systematic review of the
      literature to obtain and assess evidence toward developing clinical
      recommendations for health care professionals related to the diagnosis,
      prognosis, and management/treatment of pediatric mTBI. Evidence Review: The
      Centers for Disease Control and Prevention (CDC) National Center for Injury
      Prevention and Control Board of Scientific Counselors, a federal advisory
      committee, established the Pediatric Mild Traumatic Brain Injury Guideline
      Workgroup. The workgroup drafted recommendations based on the evidence that was
      obtained and assessed within the systematic review, as well as related evidence,
      scientific principles, and expert inference. This information includes selected
      studies published since the evidence review was conducted that were deemed by the
      workgroup to be relevant to the recommendations. The dates of the initial
      literature search were January 1, 1990, to November 30, 2012, and the dates of
      the updated literature search were December 1, 2012, to July 31, 2015. Findings:
      The CDC guideline includes 19 sets of recommendations on the diagnosis,
      prognosis, and management/treatment of pediatric mTBI that were assigned a level
      of obligation (ie, must, should, or may) based on confidence in the evidence.
      Recommendations address imaging, symptom scales, cognitive testing, and
      standardized assessment for diagnosis; history and risk factor assessment,
      monitoring, and counseling for prognosis; and patient/family education, rest,
      support, return to school, and symptom management for treatment. Conclusions and
      Relevance: This guideline identifies the best practices for mTBI based on the
      current evidence; updates should be made as the body of evidence grows. In
      addition to the development of the guideline, CDC has created user-friendly
      guideline implementation materials that are concise and actionable. Evaluation of
      the guideline and implementation materials is crucial in understanding the
      influence of the recommendations.

PMID- 30193290
TI  - Pediatric Computed Tomography Scans and Cancer Risk.

PMID- 30193287
TI  - Validation of Haptic Properties of Materials for Endoscopic Sinus and Skull Base
      Surgery Simulation-Reply.

PMID- 30193291
TI  - Use of Long-term Cumulative Blood Pressure in Cardiovascular Risk Prediction
      Models.
AB  - Importance: Long-term cumulative systolic blood pressure (SBP) is significantly
      associated with increased rates of atherosclerotic cardiovascular disease (ASCVD)
      development independent of single SBP levels. However, published ASCVD risk
      prediction algorithms only include currently measured SBP. Objective: To
      determine whether including long-term (5- and 10-year) cumulative SBP in risk
      equations improves the predictive ability compared with single SBP measurements.
      Design, Setting, and Participants: Adults aged 45 to 65 years at the time of risk
      estimation with at least 20 years of follow-up (5 and 10 years prior to risk
      estimation and 10 years of event follow-up). The Lifetime Risk Pooling Project
      included data from the following cohorts: Coronary Artery Risk Development in
      Young Adults Study, Atherosclerosis Risk in Communities Study, and Framingham
      Heart Study (both the original and offspring). Exposures: Ten-year ASCVD risk,
      calculated using the approach of the 2013 American College of Cardiology/American
      Heart Association 10-year ASCVD risk equations, first with current SBP and then
      substituting 5- and 10-year cumulative SBP levels. Main Outcomes and Measures:
      Incident ASCVD events that occurred over 10 years of follow-up, compared with the
      predicted risks, using the C statistic, net reclassification index at event rate,
      and the integrated discrimination index. Results: This study included 11 767
      participants with a mean (SD) age of 59.1 (4.7) years at risk estimation. A total
      of 6873 participants (58%) were women, and 1499 (13%) were African American. In
      the 10 years of follow-up from risk estimation, 1887 participants (16%) had an
      ASCVD event. There were no significant improvements in the C statistic when
      including 5- or 10-year cumulative SBP. However, the addition of cumulative SBP
      resulted in significant improvements in the net reclassification index at event
      rate (10-year net reclassification index for men, 0.04 [95% CI, 0.02-0.06]; 10
      year net reclassification index for women, 0.03 [95% CI, 0.01-0.06]) and the
      relative integrated discrimination index (10-year relative integrated
      discrimination index for men, 0.12; 10-year relative integrated discrimination
      index for women, 0.10). Conclusions and Relevance: Using long-term measures of
      cumulative blood pressure, instead of single measurements, can modestly improve
      the ability of cardiovascular disease risk prediction models to correctly
      classify individuals in terms of their risk for cardiovascular disease.

PMID- 30193292
TI  - A Bowl of Oranges.

PMID- 30193293
TI  - Comparison of Opioid Utilization Patterns After Major Head and Neck Procedures
      Between Hong Kong and the United States.
AB  - Importance: The current opioid abuse epidemic in the United States requires
      evaluation of prescribing practices within all medical specialties. This
      examination includes a review of postoperative pain management for patients
      undergoing major head and neck procedures. Objective: To report differences in
      postoperative pain regimens between an international and domestic head and neck
      surgical program. Design, Setting, and Participants: Pain management patterns
      after head and neck surgery in the programs at Chinese University of Hong Kong
      (CUHK) and Oregon Health and Science University (OHSU) were compared with a focus
      on opioids, nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen or
      paracetamol, and anxiolytics. Cases from July 1, 2013, through August 31, 2017,
      were reviewed. Standing medication orders the day before surgery (PRE1),
      postoperative day 6 (POD6), and postoperative day 14 (POD14) were compared
      between institutions. Exposures: Head and neck surgery. Results: A total of 253
      cases from CUHK and 567 cases from OHSU were analyzed (mean [SD] age, 59.4 [14.3]
      and 60.1 [16.4] years, respectively). Patients from OHSU had a significantly
      higher frequency of opioid orders on PRE1 (15.3% vs 1.6%; odds ratio [OR], 11.3;
      95% CI, 4.09-31.10), POD6 (86.8% vs 0.4%; OR, 1653.12; 95% CI, 228.51-11 959.01),
      and POD14 (71.4% vs 0.8%; OR, 313.75; 95% CI, 77.12-1276.52). There were no
      significant differences in acetaminophen or paracetamol, NSAID, or anxiolytic
      orders between institutions. Institution was the most significant indicator for
      the presence of opioid orders on POD6 (OR, 4271.10; 95% CI, 380.04-47 999.70) and
      POD14 (OR, 330.35; 95% CI, 79.67-1369.82). In addition to treating institution,
      multivariate analysis showed that PRE1 opioid orders indicated a significant
      increase in likelihood of opioid orders on POD6 (OR, 4.77; 95% CI, 1.23-18.57)
      but not POD14. POD6 anxiolytic orders remained a significant indicator of opioid
      orders for POD6 (95% CI, 1.49-113.10) and POD14 (95% CI, 1.17-5.03),
      respectively. Conclusions and Relevance: A significantly lower frequency of
      postoperative opioid orders was observed from CUHK compared with OHSU across
      similar major head and neck procedures. This contrast encourages a careful
      examination of (1) cultural and patient expectations of pain control, (2) the
      metrics by which control is assessed, (3) industry and economic drivers of opioid
      use, and (4) alternatives to opioid pain regimens. A thoughtful shift in
      postoperative pain protocols that deemphasizes opioid use may be an opportunity
      to counter the epidemic of opioid abuse in the United States.

PMID- 30193295
TI  - Disease-Free and Overall Survival Among Patients With Operable HER2-Positive
      Breast Cancer Treated With Sequential vs Concurrent Chemotherapy: The ACOSOG
      Z1041 (Alliance) Randomized Clinical Trial.
AB  - Importance: Pathologic complete response rate (pCR), the primary end point of the
      ACOSOG (American College of Surgeons Oncology Group) Z1041 (Alliance) trial, and
      disease-free survival (DFS) and overall survival (OS) in women with operable HER2
      positive breast cancer are similar between treatment regimens. Objective: To
      assess DFS and OS for patients treated with sequential vs concurrent
      anthracycline plus trastuzumab. Design, Setting, and Participants: Phase 3
      randomized clinical trial conducted at 36 centers in the continental United
      States and Puerto Rico. Women 18 years or older with invasive operable HER2
      positive breast cancer were enrolled from September 15, 2007, to December 15,
      2011, and randomized to 1 of 2 treatment arms. The analysis data set was locked
      on October 15, 2017, and analysis was completed on December 15, 2017.
      Interventions: Patients randomized to arm 1 received 500 mg/m2 of fluorouracil,
      75 mg/m2 of epirubicin, and 500 mg/m2 of cyclophosphamide (FEC) every 3 weeks for
      12 weeks followed by the combination of 80 mg/m2 of paclitaxel and 2 mg/kg
      (except initial dose of 4 mg/kg) of trastuzumab weekly for 12 weeks. Patients
      randomized to arm 2 received the same combination of paclitaxel with trastuzumab
      weekly for 12 weeks followed by FEC every 3 weeks with weekly trastuzumab for 12
      weeks. Women with hormone receptor-positive disease received endocrine therapy,
      and radiotherapy was delivered at physician discretion. Main Outcomes and
      Measures: The primary outcomes were DFS and OS and pCR in the breast and nodes.
      Results: Two hundred eighty-two women with HER2-positive breast cancer were
      enrolled in the trial, and 2 withdrew consent before treatment. Among the
      remaining 280 women, the median age was 50 years (range, 28-76 years), 232
      (82.9%) were white, 29 (10.3%) were black, 8 (2.9%) were Asian, 4 (1.4%) were
      American Indian or Alaskan Native, and 7 (2.5%) did not report race/ethnicity.
      There were 22 disease events in arm 1 and 27 in arm 2. Disease-free survival
      rates did not differ with respect to treatment arm (stratified log-rank P = .96;
      stratified hazard ratio [HR] [arm 2 to arm 1], 1.02; 95% CI, 0.56-1.83). Overall
      survival did not differ with respect to treatment arm (stratified log-rank P =
      .73; stratified HR [arm 2 to arm 1], 1.17; 95% CI, 0.48-2.88). Conclusions and
      Relevance: Across a median follow-up of 5.1 years (range, 26 days to 6.2 years),
      pCR, DFS, and OS did not differ with respect to sequential or concurrent
      administration of FEC with trastuzumab. Trial Registration: ClinicalTrials.gov
      identifier: NCT00513292.

PMID- 30193296
TI  - State of the Science on Pediatric Mild Traumatic Brain Injury: Progress Toward
      Clinical Translation.

PMID- 30193297
TI  - Preoperative Imaging Techniques in Primary Hyperparathyroidism: A Review.
AB  - Importance: Successful minimally invasive parathyroidectomy requires confident
      and accurate preoperative localization. Several noninvasive imaging techniques
      are well established for preoperative localization, and others are emerging.
      Observations: Ultrasonography and sestamibi imaging are established preoperative
      localization techniques with good sensitivity and positive predictive value.
      Multiphase 4-dimensional computed tomography is a newer technique with arguably
      superior performance, particularly in the setting of negative or discordant
      ultrasonography and sestamibi imaging, residual or recurrent primary
      hyperparathyroidism following a previous surgical operation, and multiglandular
      disease. Emerging techniques that may further facilitate confident and accurate
      preoperative localization include ultrasonography, elastography, positron
      emission tomography, and 4-D magnetic resonance imaging. Conclusions and
      Relevance: The optimal imaging localization algorithm for hyperparathyroidism
      remains undetermined, but a combination of techniques tailored to the specific
      scenario will likely yield the best outcomes. An algorithm is proposed that
      considers test performance, surgeon confidence, patient-specific factors, cost,
      local radiologic expertise, and patient radiation exposure.

PMID- 30193294
TI  - Effect of Group-Administered Behavioral Treatment on Urinary Incontinence in
      Older Women: A Randomized Clinical Trial.
AB  - Importance: Urinary incontinence (UI) guidelines recommend behavioral
      interventions as first-line treatment using individualized approaches. A one
      time, group-administered behavioral treatment (GBT) could enhance access to
      behavioral treatment. Objective: To compare the effectiveness, cost, and cost
      effectiveness of GBT with no treatment for UI in older women. Design, Setting,
      and Participants: Multisite randomized clinical trial (the Group Learning
      Achieves Decreased Incidents of Lower Urinary Symptoms [GLADIOLUS] study),
      conducted from July 7, 2014, to December 31, 2016. The setting was outpatient
      practices at 3 academic medical centers. Community-dwelling women 55 years or
      older with UI were recruited by mail and screened for eligibility, including a
      score of 3 or higher on the International Consultation on Incontinence
      Questionnaire-Short Form (ICIQ-SF), symptoms of at least 3 months' duration, and
      absence of medical conditions or treatments that could affect continence status.
      Of 2171 mail respondents, 1125 were invited for clinical screening; 463 were
      eligible and randomized; 398 completed the 12-month study. Interventions: The GBT
      group received a one-time 2-hour bladder health class, supported by written
      materials and an audio CD. Main Outcomes and Measures: Outcomes were measured at
      in-person visits (at 3 and 12 months) and by mail or telephone (at 6 and 9
      months). The primary outcome was the change in the ICIQ-SF score. Secondary
      outcome measures assessed UI severity, quality of life, perceptions of
      improvement, pelvic floor muscle strength, and costs. Evaluators were masked to
      group assignment. Results: Participants (232 in the GBT group and 231 in the
      control group) were aged 55 to 91 years (mean [SD] age, 64 [7] years), and 46.2%
      (214 of 463) were African American. In intent-to-treat analyses, the ICIQ-SF
      scores for GBT were consistently lower than control across all time points but
      did not achieve the projected 3-point difference. At 3 months, the difference in
      differences was 0.96 points (95% CI, -1.51 to -0.41 points), which was
      statistically significant but clinically modest. The mean (SE) treatment effects
      at 6, 9, and 12 months were 1.36 (0.32), 2.13 (0.33), and 1.77 (0.31),
      respectively. Significant group differences were found at all time points in
      favor of GBT on all secondary outcomes except pelvic floor muscle strength. The
      incremental cost to achieve a treatment success was $723 at 3 months; GBT
      dominated at 12 months. Conclusions and Relevance: The GLADIOLUS study shows that
      a novel one-time GBT program is modestly effective and cost-effective for
      reducing UI frequency, severity, and bother and improving quality of life. Group
      administered behavioral treatment is a promising first-line approach to enhancing
      access to noninvasive behavioral treatment for older women with UI. Trial
      Registration: ClinicalTrials.gov identifier: NCT02001714.

PMID- 30193298
TI  - Mechanisms of Cell-to-Cell Transmission of Pathological Tau: A Review.
AB  - Importance: Intracellular tau protein aggregates are a pathological hallmark of
      neurodegenerative tauopathies, including Alzheimer disease (AD), progressive
      supranuclear palsy (PSP), corticobasal degeneration (CBD), and Pick disease.
      Emerging evidence supports a model of cell-to-cell transmission of proteinaceous
      pathological tau seeds, which leads to recruitment and templated fibrillization
      of endogenous cellular tau followed by the spread of abnormal tau throughout the
      brain. These findings lead to the strain hypothesis, which predicts that distinct
      conformational strains or polymorphs of tau may underlie the clinical and
      neuropathological heterogeneity and cell-type specificity of tauopathies. In this
      review, we describe the evidence for propagation of distinct tau strains in cell
      culture and animal models of AD and mechanistic insights into cell-to-cell
      transmission of pathological tau. Observations: Intracranial injections of
      synthetic tau-preformed fibrils and human brain-derived pathological tau into
      nontransgenic wild-type mice and transgenic mouse models of AD expressing beta
      amyloid and tau-amyloid deposits yield widespread pathological tau aggregates
      observed in neuroanatomically connected brain regions distant from the site of
      injection. Furthermore, when human brain-derived pathological tau obtained from
      distinct tauopathies (ie, brains with AD, PSP, and CBD) were injected into the
      brains of wild-type mice, they seeded tau pathology and faithfully recapitulated
      cell-type specific tau inclusions characteristic of each tauopathy in a time
      dependent, dose-dependent, and injection site-dependent spread reflective of the
      connectome of the injection site. Conclusions and Relevance: These findings
      provide compelling evidence that misfolded or pathological conformers of tau
      undergo cell-to-cell spread in a tauopathy strain-specific manner. Importantly,
      evidence to date supports that pathological tau strains do not behave like
      infectious agents, despite growing evidence that these tau strains undergo
      templated propagation and spread linked to the neuroanatomical connectome of the
      injection site.

PMID- 30193299
TI  - Symptom Burden Associated With Late Lower Cranial Neuropathy in Long-term
      Oropharyngeal Cancer Survivors.
AB  - Importance: Lower cranial neuropathy (LCNP) is a rare but potentially disabling
      result of radiotherapy and other head and neck cancer therapies. Survivors who
      develop late LCNP may experience profound functional impairment, with deficits in
      swallowing, speech, and voice. Objective: To investigate the association of late
      LCNP with severity of cancer treatment-related symptoms and subsequent general
      functional impairment among oropharyngeal cancer (OPC) survivors. Design,
      Setting, and Participants: This cross-sectional survey study analyzed 889 OPC
      survivors nested within a retrospective cohort of OPC survivors treated at MD
      Anderson Cancer Center from January 1, 2000, to December 31, 2013. Eligible
      survey participants were disease free and completed OPC treatment 1 year or more
      before the survey. Data analysis was performed from October 10, 2017, to March
      15, 2018. Exposures: Late LCNP defined by onset 3 months or more after cancer
      therapy. Main Outcomes and Measures: The primary outcome variable was the mean of
      the top 5 most severely scored symptoms of all 22 core and head and neck cancer
      specific symptoms from the MD Anderson Symptom Inventory Head and Neck Cancer
      Module (MDASI-HN). Secondary outcomes included mean MDASI-HN interference scores
      and single-item scores of the most severe symptoms. Multivariate models regressed
      MDASI-HN scores on late LCNP status, adjusting for clinical covariates. Results:
      Overall, 36 of 889 OPC survivors (4.0%) (753 [84.7%] male; 821 [92.4%] white;
      median [range] age, 56 [32-84] years; median [range] survival time, 7 [1-16]
      years) developed late LCNP. Late LCNP was significantly associated with worse
      mean top 5 MDASI-HN symptom scores (coefficient, 1.54; 95% CI, 0.82-2.26),
      adjusting for age, survival time, sex, therapeutic modality, T stage, subsite,
      type of radiotherapy, smoking, and normal diet before treatment. Late LCNP was
      also significantly associated with single-item scores for difficulty swallowing
      or chewing (coefficient, 2.25; 95% CI, 1.33-3.18), mucus (coefficient, 1.97; 95%
      CI, 1.03-2.91), fatigue (coefficient, 1.35; 95% CI, 0.40-2.21), choking
      (coefficient, 1.53; 95% CI, 0.65-2.41), and voice or speech symptoms
      (coefficient, 2.30; 95% CI, 1.60-3.03) in multivariable models. Late LCNP was not
      significantly associated with mean interference scores after correction for
      multiple comparisons (mean interference coefficient, 0.72; 95% CI, 0.09-1.35).
      Conclusions and Relevance: In this large survey study, OPC survivors with late
      LCNP reported worse cancer treatment-related symptoms, a finding suggesting an
      association between late LCNP and symptom burden. This research may inform the
      development and implementation of strategies for LCNP surveillance and
      management.

PMID- 30193300
TI  - Assessment of Treatment of Refractory Granuloma Faciale With Intralesional
      Rituximab.
AB  - Importance: Granuloma faciale (GF) is a rare, benign inflammatory dermatosis of
      unknown cause. Some reports have suggested that it could be part of the spectrum
      of IgG4-related sclerosing diseases. Granuloma faciale is characterized by single
      or multiple red-brown nodules, most frequently occurring on the face, and it can
      produce severe disfigurement. Treatment is difficult, and poor outcomes are often
      seen. Rituximab is a monoclonal antibody against CD-20 approved by the US Food
      and Drug Administration for treatment of some autoimmune and tumoral diseases.
      Objective: To evaluate the treatment of refractory GF with intralesional
      rituximab. Design, Setting, and Participants: In this case series, 3 patients
      with biopsy-proved refractory GF who underwent treatment at a dermatology
      outpatient clinic of a tertiary referral hospital were evaluated. The study was
      conducted from August 2015 to December 2017. Interventions: Doses of 0.5 to 1
      mL/cm2 of intralesional rituximab, 10 mg/mL, were administered monthly for 6
      months and thereafter depending on clinical response. In 2 patients, peripheral
      blood B-cell counts were monitored before and during treatment, and in 1 patient,
      only during treatment. Main Outcomes and Measures: Reduction in size of the
      lesions, ultrasonography evaluation, subjective improvement, and adverse events
      were monitored throughout the course of therapy. Results: All 3 of the patients
      were men (ages from 30s to 60s). They showed a significant reduction in the size
      and thickness of GF both clinically and on ultrasonography evaluation. Two
      patients had a complete response and the third, a partial response. A reduction
      in peripheral blood B-cell count was observed in the 3 patients, suggesting that
      the action of rituximab could be systemic. No severe adverse reactions were
      reported. Conclusions and Relevance: Intralesional rituximab may represent a
      novel and well-tolerated therapy for refractory GF.

PMID- 30193301
TI  - Clarification on Uveal Melanoma Associated With Myotonic Dystrophy.

PMID- 30193302
TI  - A Randomized Clinical Trial of n-of-1 Trials-Tribulations of a Trial.

PMID- 30193303
TI  - Comparative Effectiveness and Safety of Bariatric Procedures in Medicare-Eligible
      Patients: A Systematic Review.
AB  - Importance: The prevalence of obesity in patients older than 65 years is
      increasing. A substantial number of beneficiaries covered by Medicare meet
      eligibility criteria for bariatric procedures. Objective: To assess the
      comparative effectiveness and safety of bariatric procedures in the Medicare
      eligible population. Evidence Review: This systematic review was conducted
      according to the PRISMA guidelines. Articles were identified through searches of
      PubMed, Embase, CINAHL, PsycINFO, Cochrane Central Trials Registry, Cochrane
      Database of Systematic Reviews, and scientific information packages from
      manufacturers, ClinicalTrials.gov, World Health Organization International
      Clinical Trials Registry Platform, and US Food and Drug Administration drugs and
      devices portals from January 1, 2000, to June 31, 2017. Randomized and
      nonrandomized comparative studies that evaluated bariatric procedures in the
      Medicare-eligible population were eligible. Six researchers extracted data on
      design, interventions, outcomes, and study quality. Findings were synthesized
      qualitatively; a planned meta-analysis was not undertaken owing to clinical
      heterogeneity. Findings: A total of 11 455 citations were screened for
      eligibility. Of those, 16 met the eligibility criteria. Compared with no surgery
      or conventional weight-loss treatment, bariatric surgery results in greater
      weight loss. Overall mortality after 30 days is lower among bariatric patients
      (hazard ratio, HR, 0.50; 95% CI, 0.31-0.79, in the study with the longest follow
      up of 5.9 years), although, based on 1 study, mortality within 30 days of surgery
      was higher than in nonsurgically treated controls (1.55% vs 0.53%; P < .001).
      Bariatric surgery is associated with lower risk of cardiovascular disease (HR,
      0.59; 95% CI, 0.44-0.79 in the largest study comparison) and with improvements in
      respiratory, musculoskeletal, metabolic, and renal outcomes (increase in
      estimated glomerular filtration rate, 9.84; 95% CI, 8.05-11.62 mL/min/1.73m2).
      Compared with sleeve gastrectomy (SG) and adjustable gastric banding (AGB), Roux
      en-Y gastric bypass (RYGB) appears to be associated with greater weight loss
      (percent excess weight loss, 23.8% [95% CI, 16.2%-31.4%] at the longest follow-up
      of 4 years) but the 3 procedures have similar associations with most non-weight
      loss outcomes. Overall postoperative complications are not statistically
      significantly different between RYGB and SG, although major and/or serious
      complications are more common after RYGB. However, these associations are
      susceptible to at least moderate risk of confounding, selection, or measurement
      biases. Conclusions and Relevance: In the Medicare population, there is low to
      moderate strength of evidence that bariatric surgery as a weight loss treatment
      improves non-weight loss outcomes. Well-designed comparative studies are needed
      to credibly determine the treatment effects for bariatric procedures in this
      patient population.

PMID- 30193304
TI  - Million Hearts 2022: Small Steps Are Needed for Cardiovascular Disease
      Prevention.

PMID- 30193305
TI  - Three-Dimensional Microscopy Demonstrates Series and Parallel Organization of
      Human Peripapillary Capillary Plexuses.
AB  - Purpose: To define the three-dimensional topologic organization of the human
      peripapillary capillary plexuses in order to better understand the hemodynamic
      characteristics of this retinal circulation. Methods: The retinal
      microvasculature was perfusion labeled in five normal human donor eyes, and
      optical stacks were collected from regions immediately superior, temporal,
      inferior, and nasal to the optic disk by using confocal scanning laser
      microscopy. The spatial location and morphometric characteristics of capillary
      plexuses were compared. Three-dimensional visualization strategies were used to
      document the organization of vascular conduits that interconnect capillary beds
      and to study the communications between capillary beds and precapillary
      arterioles and postcapillary venules. Results: The peripapillary microcirculation
      is composed of four capillary plexuses, including the radial peripapillary
      capillary plexus at the level of the nerve fiber layer, the superficial capillary
      plexus (SCP) at the level of the ganglion cell layer, the intermediate capillary
      plexus located at the inner boundary of the inner nuclear layer, and the deep
      capillary plexus located at the outer boundary of the inner nuclear layer.
      Capillary diameter and density were significantly different between the four
      plexuses (both P <= 0.011). The SCP is the only capillary bed that receives
      feeding and draining branches directly from precapillary arterioles and
      postcapillary venules, respectively. Four different inflow and outflow patterns
      characterized the communication between the SCP and surrounding capillary beds.
      Conclusions: The capillary plexuses of the human peripapillary microcirculation
      are arranged in series and parallel and manifest specializations that likely
      reflect the unique metabolic demands and biochemical environment of the retinal
      layers.

PMID- 30193306
TI  - Corneal Neurotization Improves Ocular Surface Health in a Novel Rat Model of
      Neurotrophic Keratopathy and Corneal Neurotization.
AB  - Purpose: Corneal neurotization is a novel surgical procedure to reinnervate the
      cornea in patients with neurotrophic keratopathy (NK). We developed a rat model
      of NK and corneal neurotization to further investigate corneal neurotization as a
      treatment to improve maintenance and healing of the corneal epithelium. Methods:
      Thy1-GFP+ Sprague Dawley rats were used to develop the model. Corneal denervation
      was performed via stereotactic electrocautery of the ophthalmomaxillary branch of
      the trigeminal nerve. Corneal neurotization was performed by guiding donor
      sensory axons from the contralateral infraorbital nerve into the cornea via two
      nerve grafts. Corneal imaging, including nerve density measurements and
      retrograde labeling were performed to validate the model. In vivo assays of
      corneal maintenance and repair were used to examine whether treatment with
      corneal neurotization improved healing in rats with NK. Results: Corneal
      neurotization significantly increased corneal axon density in rats with NK (P <
      0.01). Retrograde labeling of the cornea in rats with corneal neurotization
      labeled 206 +/- 82 neurons in the contralateral trigeminal ganglion, confirming
      axons reinnervating the cornea derived from the contralateral infraorbital nerve.
      Corneal reinnervation after corneal neurotization improved corneal epithelial
      maintenance and corneal healing after injury (P < 0.01). Conclusions: Donor nerve
      fibers reinnervate the insensate cornea after corneal neurotization and
      significantly improve corneal maintenance and repair. This model can be used to
      further investigate how corneal neurotization influences epithelial maintenance
      and repair in the context of NK.

PMID- 30193307
TI  - A Metabolomics Profiling of Glaucoma Points to Mitochondrial Dysfunction,
      Senescence, and Polyamines Deficiency.
AB  - Purpose: To determine the plasma metabolomic signature of primary open-angle
      glaucoma (POAG). Methods: We compared the metabolomic profiles of plasma from
      individuals with POAG (n = 36) with age- and sex-matched controls with cataract
      (n = 27). A targeted metabolomics study was performed using the standardized p180
      Biocrates Absolute IDQ p180 kit with a QTRAP 5500 mass spectrometer. Multivariate
      analyses were performed using principal component analysis (PCA) and the least
      absolute shrinkage and selection operator (LASSO) method. Results: Among the 151
      metabolites accurately measured, combined univariate and multivariate analyses
      revealed 18 discriminant metabolites belonging to the carbohydrate, acyl
      carnitine, phosphatidylcholine, amino acids, and polyamine families. The
      metabolomic signature of POAG points to three closely interdependent
      pathophysiologic conditions; that is, defective mitochondrial oxidation of
      energetic substrates, altered metabolism resembling that observed in senescence,
      and a deficiency in spermidine and spermine, both polyamines being involved in
      the protection of retinal ganglion cells. Conclusions: Our results highlight a
      systemic and age-related mitochondrial defect in the pathogenesis of POAG.

PMID- 30193308
TI  - Photoreceptor Survival Is Regulated by GSTO1-1 in the Degenerating Retina.
AB  - Purpose: Glutathione-S-transferase omega 1-1 (GSTO1-1) is a cytosolic glutathione
      transferase enzyme, involved in glutathionylation, toll-like receptor signaling,
      and calcium channel regulation. GSTO1-1 dysregulation has been implicated in
      oxidative stress and inflammation, and contributes to the pathogenesis of several
      diseases and neurological disorders; however, its role in retinal degenerations
      is unknown. The aim of this study was to investigate the role of GSTO1-1 in
      modulating oxidative stress and consequent inflammation in the normal and
      degenerating retina. Methods: The role of GSTO1-1 in retinal degenerations was
      explored by using Gsto1-/- mice in a model of retinal degeneration. The
      expression and localization of GSTO1-1 were investigated with
      immunohistochemistry and Western blot. Changes in the expression of inflammatory
      (Ccl2, Il-1beta, and C3) and oxidative stress (Nox1, Sod2, Gpx3, Hmox1, Nrf2, and
      Nqo1) genes were investigated via quantitative real-time polymerase chain
      reaction. Retinal function in Gsto1-/- mice was investigated by using
      electroretinography. Results: GSTO1-1 was localized to the inner segment of cone
      photoreceptors in the retina. Gsto1-/- photo-oxidative damage (PD) mice had
      decreased photoreceptor cell death as well as decreased expression of
      inflammatory (Ccl2, Il-1beta, and C3) markers and oxidative stress marker Nqo1.
      Further, retinal function in the Gsto1-/- PD mice was increased as compared to
      wild-type PD mice. Conclusions: These results indicate that GSTO1-1 is required
      for inflammatory-mediated photoreceptor death in retinal degenerations. Targeting
      GSTO1-1 may be a useful strategy to reduce oxidative stress and inflammation and
      ameliorate photoreceptor loss, slowing the progression of retinal degenerations.

PMID- 30193309
TI  - Sensitivity to Velocity- and Disparity-Based Cues to Motion-In-Depth With and
      Without Spared Stereopsis in Binocular Visual Impairment.
AB  - Purpose: Two binocular sources of information serve motion-in-depth (MID)
      perception: changes in disparity over time (CD), and interocular velocity
      differences (IOVD). While CD requires the computation of small spatial
      disparities, IOVD could be computed from a much lower-resolution signal. IOVD
      signals therefore might still be available under conditions of binocular vision
      impairment (BVI) with limited or no stereopsis, for example, amblyopia. Methods:
      Sensitivity to CD and IOVD was measured in adults who had undergone therapy to
      correct optical misalignment or amblyopia in childhood (n = 16), as well as
      normal vision controls with good stereoacuity (n = 8). Observers discriminated
      the interval containing a smoothly oscillating MID "test" stimulus from a
      "control" stimulus in a two-interval forced choice paradigm. Results: Of the BVI
      observers with no static stereoacuity (n = 9), one displayed evidence for
      sensitivity to IOVD only, while there was otherwise no sensitivity for either CD
      or IOVD in the group. Generally, BVI observers with measurable stereoacuity (n =
      7) displayed a pattern resembling the control group: showing a similar
      sensitivity for both cues. A neutral density filter placed in front of the fixing
      eye in a subset of BVI observers did not improve performance. Conclusions: In one
      BVI observer there was preserved sensitivity to IOVD but not CD, though overall
      only those BVI observers with at least gross stereopsis were able to detect
      disparity- or velocity-based cues to MID. The results imply that these logically
      distinct information sources are somehow coupled, and in some cases BVI observers
      with no stereopsis may still retain sensitivity to IOVD.

PMID- 30193310
TI  - Clinical Characterization of 66 Patients With Congenital Retinal Disease Due to
      the Deep-Intronic c.2991+1655A>G Mutation in CEP290.
AB  - Purpose: To describe the phenotypic spectrum of retinal disease caused by the
      c.2991+1655A>G mutation in CEP290 and to compare disease severity between
      homozygous and compound heterozygous patients. Methods: Medical records were
      reviewed for best-corrected visual acuity (BCVA), age of onset, fundoscopy
      descriptions. Foveal outer nuclear layer (ONL) and ellipsoid zone (EZ) presence
      was assessed using spectral-domain optical coherence tomography (SD-OCT).
      Differences between compound heterozygous and homozygous patients were analyzed
      based on visual performance and visual development. Results: A total of 66
      patients were included. The majority of patients had either light perception or
      no light perception. In the remaining group of 14 patients, median BCVA was
      20/195 Snellen (0.99 LogMAR; range 0.12-1.90) for the right eye, and 20/148
      Snellen (0.87 LogMAR; range 0.22-1.90) for the left. Homozygous patients tended
      to be more likely to develop light perception compared to more severely affected
      compound heterozygous patients (P = 0.080) and are more likely to improve from no
      light perception to light perception (P = 0.022) before the age of 6 years. OCT
      data were available in 12 patients, 11 of whom had retained foveal ONL and EZ
      integrity up to 48 years (median 23 years) of age. Conclusions: Homozygous
      patients seem less severely affected compared to their compound-heterozygous
      peers. Improvement of visual function may occur in the early years of life,
      suggesting a time window for therapeutic intervention up to the approximate age
      of 17 years. This period may be extended by an intact foveal ONL and EZ on OCT.

PMID- 30193311
TI  - Posterior Choroidal Stroma Reduces Accuracy of Automated Segmentation of Outer
      Choroidal Boundary in Swept Source Optical Coherence Tomography.
AB  - Purpose: To determine the influence of choroidal boundary morphology on the
      accuracy of automated measurements of subfoveal choroidal thickness (SFCT) in
      swept source optical coherence tomography (SSOCT). Methods: A retrospective image
      analysis of foveal-centered horizontal line scans from normal and diseased eyes
      using the Topcon DRI OCT-1 Atlantis SSOCT was conducted. Subfoveal choroid
      scleral junction (CSJ) and retina-choroidal junction (RCJ) morphologies were
      graded by two observers. Automated SFCT (A-SFCT) was compared with manual SFCT (M
      SFCT) measurements from Bruch's membrane to the posterior limits of choroidal
      vessel, hyperreflective stroma, and hyporeflective lamina fusca. Agreement in
      boundary grading was assessed by Cohen's kappa. A-SFCT and M-SFCT were compared
      using Bland-Altman analysis and paired t-tests. Results: A total of 200 eyes of
      100 patients with a mean (SD) age of 62 (18) years were included. The choroidal
      vessel, stromal, and lamina fusca boundaries were visible in 100%, 58%, and 38%
      of the eyes, respectively. Interobserver agreement in RCJ and CSJ grading was
      high (kappa = 0.974 and 0.851). Mean A-SFCT differed from M-SFCT by only 2 MUm at
      posterior choroidal vessel boundary (P = 0.801). A-SFCT overestimated SFCT at the
      posterior vessel wall boundary by 17 MUm (P = 0.026) and 23 MUm (P = 0.001) in
      the presence of a visible posterior choroidal stroma and lamina fusca,
      respectively. Conclusions: Automated outer choroidal boundary segmentation tends
      to identify the posterior limit of the choroidal vessel. Agreement between A-SFCT
      and M-SFCT is reduced by the presence of posterior stromal layer and lamina
      fusca. A-SFCT should be interpreted with RCJ and CSJ boundary grading.

PMID- 30193312
TI  - Effects of Light of Different Spectral Composition on Refractive Development and
      Retinal Dopamine in Chicks.
AB  - Purpose: There is ample evidence that retinal dopamine (DA) is involved in the
      biochemical signaling cascade that controls emmetropization, but it is unknown
      how its release depends on the spectral composition of ambient light. We have
      studied DA release, refractive development, and growth in chicken eyes that were
      exposed to light of different spectral bands, and had either normal vision or
      were covered by frosted diffusers to induce myopia. Methods: Experiment 1: After
      spending the night in the dark, chicks were exposed to white room light (spectral
      range, 430-630 nm) or kept in the dark. Additional chicks were unilaterally
      exposed to blue (peak at 470 nm), red (620 nm), or UV lighting (375 nm) for 30
      minutes and their fellow eyes covered with black occluders to minimize light
      exposure. Experiment 2: In the second experiment, chicks wore diffusers over one
      eye to induce deprivation myopia and were raised for 5 days in either white room
      light or in lighting supplied by UV, blue, or red light-emitting diodes (LEDs).
      Refractive states were recorded daily with infrared photoretinoscopy, and ocular
      dimensions at the start and end of the experiment with A-scan ultrasonography. DA
      and its metabolites were measured in retina and vitreous by high pressure liquid
      chromatography-electrochemical detection (HPLC-ED) in all cases. Results:
      Compared to chicks kept in the dark, retinal DA and vitreal 3,4
      dihydroxyphenylacetic acid (DOPAC) concentrations were clearly elevated after 30
      minutes in white light. Vitreal DOPAC was also increased in red, blue, and UV
      lighting, compared to the fellow eyes covered with black occluders (black
      occluder versus blue light: 1.31 +/- 0.32 vs. 1.70 +/- 0.37; red: 1.26 +/- 0.33
      vs. 1.64 +/- 0.38; UV: 1.13 +/- 0.19 vs. 1.63 +/- 0.21 ng/0.1 g wet weight).
      Chickens developed significantly less deprivation myopia, with shorter eyes, when
      raised under UV and blue lighting for 5 days, compared to under red and white
      light. Eyes with normal vision became more hyperopic in blue and UV lighting.
      Vitreal DOPAC levels were lowest after 5 days of exposure to UV lighting.
      Conclusions: Red, blue, and UV lighting all stimulated the release of retinal DA,
      but there were wavelength-dependent differences in DA release and metabolism.
      Less deprivation myopia developed in UV and blue lighting, compared to white and
      red light. The application of these findings to humans is limited by the fact
      that, different from chicks, humans have very low sensitivity in the near-UV
      region of the spectrum.

PMID- 30193313
TI  - Retinal Vascular Reactivity in Central Serous Chorioretinopathy.
AB  - Purpose: To investigate the retinal vascular response to the isometric exercise
      in patients with central serous chorioretinopathy (CSCR) by using optical
      coherence tomography angiography (OCT-A). Methods: This was a multicenter case
      control study including 35 CSCR patients and 25 age-matched healthy controls. All
      subjects underwent macular OCT-A scans in resting conditions and during a
      handgrip isometric exercise. Hemodynamic data, such as systolic blood pressure
      (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and ocular
      perfusion pressure (OPP), were recorded at baseline and during the stress test.
      Qualitative and quantitative assessments of the retinal superficial capillary
      plexus (SCP) and deep capillary plexus (DCP) were performed on OCT angiograms.
      The results obtained in CSCR patients were then compared with those of healthy
      subjects. Results: At baseline and during the isometric exercise, SBP, DBP, MAP,
      and OPP were significantly higher (P < 0.05) in CSCR patients than controls.
      Under stress conditions, the hemodynamic values significantly increased both in
      patients and controls. The qualitative and quantitative analyses of OCT
      angiograms evidenced an increased blood flow during exercise only in CSCR
      patients. Baseline vascular perfusion density (VPD) values of SCP and DCP were
      significantly lower (P < 0.05) in CSCR cases than in healthy subjects. A
      significant increase (P < 0.05) of VPD values was obtained during the exercise in
      CSCR patients and not in controls. Conclusions: Unlike healthy subjects, retinal
      blood flow in patients with CSCR seems affected by rapid increases in BP and OPP.
      Our study suggests that the autoregulatory mechanisms controlling retinal
      microcirculation are not entirely able to counteract overperfusion in patients
      with CSCR.

PMID- 30193314
TI  - Development of High-Throughput Clinical Testing of RPGR ORF15 Using a Large
      Inherited Retinal Dystrophy Cohort.
AB  - Purpose: Mutations in the ORF15 region of RPGR account for approximately half of
      all X-linked retinitis pigmentosa cases. However, a robust high-throughput method
      for the detection of ORF15 mutations has yet to be validated. We set out to
      develop the first clinically validated next-generation sequencing (NGS) method
      for the detection of mutations in this difficult-to-sequence region, including
      test accuracy and coverage data. Methods: As part of a blind-test, 145 research
      samples, previously tested by Sanger sequencing, and 81 clinical samples were
      evaluated using NGS of long-range PCR products fragmented with Illumina's Nextera
      library preparation kit (method 1), or with Centrillion's OneTube technology,
      supplemented with duplication analysis using an ORF15-specific in-silico array
      (method 2). DNA fragments were analyzed using Agilent's DNA 1000 assay, and
      sequencing was done on Illumina's MiSeq 2*150 or HiSeq2500 2*100. NextGENe by
      SoftGenetics was used for data analysis and variant calling. Results: The Nextera
      library preparation method produced 24 cases of discordance due to (in order of
      decreasing occurrence) false-negatives, incorrectly called variants, and a false
      positive. Subsequent use of a new, OneTube NGS library preparation method,
      supplemented with duplication analyses, resolved discordance between Sanger and
      NGS data in all cases. This improvement in variant detection accuracy was largely
      attributed to improvement in random fragmentation offered by the enzymatic
      OneTube method, resulting in more complete coverage of the highly repetitive
      ORF15 region. Minimum coverage was roughly 320 reads for Nextera and 6800 reads
      for OneTube (normalized for total read counts). Conclusions: This paper documents
      the first clinically validated NGS method for reliable, high-throughput
      sequencing of RPGR ORF15. Sensitivity and specificity of the new method were
      100%, with the caveat of unclear zygosity calling for one large duplication case.
      These findings demonstrate a reliable and practical implementation for NGS-based
      diagnosis of RPGR ORF15 mutations. They also provide the foundation for targeted,
      high-coverage sequencing of any other repetitive regions within the genome.

PMID- 30193316
TI  - The Role of Riboflavin Concentration and Oxygen in the Efficacy and Depth of
      Corneal Crosslinking.

PMID- 30193315
TI  - Dopamine Receptor Subtypes Mediate Opposing Effects on Form Deprivation Myopia in
      Pigmented Guinea Pigs.
AB  - Purpose: We reported previously that changes in dopamine receptor (DR) subtype
      activation modulate spontaneous myopia progression in albino guinea pigs. To
      determine if DR control of refractive error development is different than in its
      normal counterpart, we evaluated the contribution of dopaminergic pathways to
      emmetropization and form deprivation myopia (FDM) progression in pigmented guinea
      pigs. Methods: Monocular myopia was induced by unilateral form-deprivation (FD).
      The effects of agonists of D1R (SKF38393) and D2R (quinpirole), the corresponding
      antagonists (SCH23390 and sulpiride), and vehicle were tested by peribulbar
      injection around FD or untreated control eyes. High-performance liquid
      chromatography with electrochemical detection quantified retinal and vitreous
      dopamine (DA) and 4-dihydroxyphenylacetic acid (DOPAC) levels. Ocular refraction
      and axial dimensions were measured using eccentric infrared photoretinoscopy
      (EIR) and A-scan ultrasonography, respectively, initially and after 2 or 4 weeks
      of treatment. Results: After treatment with any of these four agents for 2 weeks,
      retinal and vitreal DA and DOPAC levels were not significantly different in drug-
      and vehicle-treated eyes. Neither agonism nor antagonism of D1R or D2R activity
      affected emmetropization. In contrast, D1R activation by SKF38393 inhibited FDM
      progression, while D2R activation by quinpirole augmented this response. On the
      other hand, D2R antagonism with sulpiride slowed FDM progression while D1R
      antagonism with SCH23390 had no effect. Conclusions: In pigmented guinea pigs,
      D1R activation inhibited, whereas D2R activation enhanced, FDM. These results
      closely mirror previous findings in albino animals and offer further evidence
      that DA and its cognate receptors affect refractive error regulation in guinea
      pigs.

PMID- 30193317
TI  - Author Response: The Role of Riboflavin Concentration and Oxygen in the Efficacy
      and Depth of Corneal Crosslinking.

PMID- 30193319
TI  - Erratum-title alt-title-type="runhead" />.

PMID- 30193318
TI  - Caspase-2 Mediates Site-Specific Retinal Ganglion Cell Death After Blunt Ocular
      Injury.
AB  - Purpose: Ocular trauma is common in civilian and military populations. Among
      other injuries, closed globe blunt ocular trauma causes acute disruption of
      photoreceptor outer segments (commotio retinae) and retinal ganglion cell (RGC)
      death (traumatic optic neuropathy [TON]), both of which permanently impair
      vision. Caspase-2-dependent cell death is important and evidenced in models of
      RGC degeneration. We assessed the role of caspase-2 as a mediator of RGC and
      photoreceptor death in a rat blunt ocular trauma model. Methods: Bilateral
      ballistic closed globe blunt ocular trauma was induced in female Lister-hooded
      rats and caspase-2 cleavage and localization assessed by Western blotting and
      immunohistochemistry. Retinal caspase-2 was knocked down by intravitreal
      injection of caspase-2 small interfering RNA (siCASP2). In retinal sections, RGC
      survival was assessed by BRN3A-positive cell counts and photoreceptor survival by
      outer nuclear layer (ONL) thickness, respectively. Retinal function was assessed
      by electroretinography (ERG). Results: Raised levels of cleaved caspase-2 were
      detected in the retina at 5, 24, and 48 hours after injury and localized to RGC
      but not photoreceptors. Small interfering RNA-mediated caspase-2 knockdown
      neuroprotected RGC around but not in the center of the injury site. In addition,
      caspase-2 knockdown increased the amplitude of the ERG photopic negative response
      (PhNR) at 2 weeks after injury. However, siCASP2 was not protective for
      photoreceptors, suggesting that photoreceptor degeneration in this model is not
      mediated by caspase-2. Conclusions: Caspase-2 mediates death in a proportion of
      RGC but not photoreceptors at the site of blunt ocular trauma. Thus,
      intravitreally delivered siCASP2 is a possible therapeutic for the effective
      treatment of RGC death to prevent TON.

PMID- 30193320
TI  - Neuroprotective Effects of FGF2 and Minocycline in Two Animal Models of Inherited
      Retinal Degeneration.
AB  - Purpose: The purpose of this study was to study the effect of minocycline and
      several neurotrophic factors, alone or in combination, on photoreceptor survival
      and macro/microglial reactivity in two rat models of retinal degeneration.
      Methods: P23H-1 (rhodopsin mutation), Royal College of Surgeon (RCS, pigment
      epithelium malfunction), and age-matched control rats (Sprague-Dawley and Pievald
      Viro Glaxo, respectively) were divided into three groups that received at P10 for
      P23H-1 rats or P33 for RCS rats: (1) one intravitreal injection (IVI) of one of
      the following neurotrophic factors: ciliary neurotrophic factor (CNTF), pigment
      epithelium-derived factor (PEDF), or basic fibroblast growth factor (FGF2); (2)
      daily intraperitoneal administration of minocycline; or (3) a combination of IVI
      of FGF2 and intraperitoneal minocycline. All animals were processed 12 days after
      treatment initiation. Retinal microglial cells and cone photoreceptors were
      immunodetected and analyzed qualitatively in cross sections. The numbers of
      microglial cells in the different retinal layers and number of nuclei rows in the
      outer nuclear layer (ONL) were quantified. Results: IVI of CNTF, PEDF, or FGF2
      improved the morphology of the photoreceptors outer segment, but only FGF2
      rescued a significant number of photoreceptors. None of the trophic factors had
      qualitative or quantitative effects on microglial cells. Minocycline treatment
      reduced activation and migration of microglia and produced a significant rescue
      of photoreceptors. Combined treatment with minocycline and FGF2 had higher
      neuroprotective effects than each of the treatments alone. Conclusions: In two
      animal models of photoreceptor degeneration with different etiologies,
      minocycline reduces microglial activation and migration, and FGF2 and minocycline
      increase photoreceptor survival. The combination of FGF2 and minocycline show
      greater neuroprotective effects than their isolated effects.

PMID- 30193321
TI  - Crystals and Fatty Acid Abnormalities Are Not Present in Circulating Cells From
      Choroideremia Patients.
AB  - Purpose: To confirm whether choroideremia (CHM) is a systemic disease
      characterized by blood lipid abnormalities and crystals found in, or associated
      with, circulating peripheral blood cells of patients. Methods: Peripheral blood
      samples obtained from three subjects with confirmed mutations in the CHM gene and
      three age-matched normal controls were processed for transmission electron
      microscopy (TEM) and scanning electron microscopy (SEM). Fatty acids from plasma
      of nine male CHM subjects were analyzed and compared to reference values for a
      sample from a Canadian population. Results: Intracellular crystals were not
      observed in the cells from choroideremia-affected males. No crystals were found
      adherent to the external plasma membrane of red blood cells. Fatty acid profiles
      of patients were similar to reference values, with the exception of lower levels
      of nervonic acid. Conclusions: This investigation failed to observe crystals
      previously reported in peripheral circulating blood cells derived from CHM
      subjects, and showed no significant fatty acid abnormalities, not supporting the
      view of CHM as a systemic disease.

PMID- 30193323
TI  - Inhibitory Effect of Idelalisib, a Selective Phosphatidylinositol 3-Kinase delta
      Inhibitor, on Adipogenesis in an In Vitro Model of Graves' Orbitopathy.
AB  - Purpose: Emerging evidence indicates that the phosphatidylinositol 3-kinase
      (PI3K)-AKT pathway is involved in the pathogenesis of Graves' orbitopathy (GO).
      In this study, the therapeutic effects of idelalisib, a selective PI3Kdelta
      inhibitor, on adipogenesis were evaluated in GO orbital fibroblasts in vitro.
      Methods: Orbital fibroblasts were cultured from orbital connective tissues
      obtained from individuals with GO and healthy control subjects. Cells were
      pretreated with idelalisib for 1 hour before stimulation with IL-1beta.
      Inflammatory cytokine expression was measured by Western blotting and ELISAs. The
      adipogenesis-related downstream mediators of the PI3K/AKT cascade, that is,
      forkhead box protein O1 (FOXO1) and mammalian target of rapamycin (mTOR), also
      were measured by Western blotting. After adipogenic differentiation and
      idelalisib treatment, cells were stained with Oil Red O and the levels of
      peroxisome proliferator activator gamma (PPARgamma) and CCAAT-enhancer-binding
      proteins (C/EBP) alpha/beta were determined by Western blot analyses. Results:
      AKT phosphorylation decreased in a dose-dependent manner upon treatment with
      idelalisib in GO and non-GO orbital fibroblasts. Treatment with idelalisib
      inhibited the IL-1beta-induced expression of IL-6 and IL-8. Idelalisib attenuated
      the phosphorylation of mTOR and FOXO1, downstream regulators of the PI3K pathway.
      Oil Red-O staining results revealed a decrease in lipid droplets and suppressed
      expression of PPARgamma and c/EBPalpha/beta upon treatment with idelalisib during
      adipose differentiation. Conclusions: Idelalisib inhibited proinflammatory
      cytokine production and adipogenesis in GO orbital fibroblasts in vitro. These
      results support the potential use of PI3K inhibitors in GO management.

PMID- 30193322
TI  - Macular Pigment and Visual Function in Patients With Glaucoma: The San Diego
      Macular Pigment Study.
AB  - Purpose: Although recent studies have shown that macular pigment (MP) is
      significantly lower in glaucoma patients, this relationship merits further
      investigation. Methods: This cross-sectional study included 85 glaucoma patients
      and 22 controls. All subjects had standard automated perimetry (SAP) and retinal
      nerve fiber layer (RNFL) thickness measurements. Intake of lutein (L) and
      zeaxanthin (Z) was estimated using a novel dietary screener. The Heidelberg
      Spectralis dual-wavelength autofluorescence (AF) technology was employed to study
      the relationship between MP and glaucoma. The association between MP volume and
      glaucoma was investigated using linear regression models accounting for potential
      confounding factors. Results: Glaucoma patients had significantly worse SAP mean
      deviation (MD) and lower RNFL thickness in the study eye compared to control
      subjects (P < 0.001 for both). MP (volume) was comparable between groups (P =
      0.436). In the univariable model, diagnosis of glaucoma was not associated with
      MP volume (R2 = 1.22%; P = 0.257). Dietary intake of L and Z was positively and
      significantly related to MP in the univariable (P = 0.022) and multivariable (P =
      0.020) models. Conclusions: These results challenge previous studies that
      reported that glaucoma is associated with low MP. Dietary habits were found to be
      the main predictor of MP in this sample. Further research is merited to better
      understand the relationship between glaucoma, MP, and visual performance in these
      patients.

PMID- 30193326
TI  - Macular Vitelliform-Like Lesion in an Eye With Chronic Retinal Detachment.

PMID- 30193328
TI  - Terminal Cancer and Death-On Grief.

PMID- 30193324
TI  - Targeting the Platelet-Derived Growth Factor-beta Stimulatory Circuitry to
      Control Retinoblastoma Seeds.
AB  - Purpose: Vitreous seeding remains the primary reason for treatment failure in
      eyes with retinoblastoma (Rb). Systemic and intra-arterial chemotherapy, each
      with its own inherent set of complications, have improved salvage rates for eyes
      with advanced disease, but the location and biology of vitreous seeds present a
      fundamental challenge in developing treatments with minimal toxicity and risk.
      The aim of this study was to target the platelet-derived growth factor (PDGF)-
      PDGF-receptor beta (PDGFRbeta) signaling pathway and investigate its role in the
      growth of Rb seeds, apoptotic activity, and invasive potential. Methods: We
      performed ex vivo analyses on vitreous samples from Rb patients that underwent
      enucleation and from patient-derived xenografts. These samples were evaluated by
      quantitative PCR, immunohistochemistry, and ELISA. The effects of disruption of
      the PDGF-PDGFRbeta signaling pathway, both by pharmacologic and genomic knockdown
      approaches, were evaluated in vitro by cell proliferation and apoptotic assays,
      quantitative PCR analyses, Western blotting, flow cytometry, and imaging flow
      cytometry. A three-dimensional cell culture system was generated for in-depth
      study of Rb seeds. Results: Our results demonstrated that PDGFRbeta signaling is
      active in the vitreous of Rb patients and patient-derived xenografts, sustaining
      growth and survival in an AKT-, MDM2-, and NF-kappaB-dependent manner. The novel
      three-dimensional cell culture system mimics Rb seeds, as the in vitro generated
      spheroids have similar morphologic features to Rb seeds and mimicked their
      natural physiology. Conclusions: Targeting the PDGFRbeta pathway in vitro reduces
      Rb cell growth, survival, and invasiveness and could augment current therapies.
      This represents a novel signaling pathway for potential targeted therapy to
      further improve ocular survival in advanced Rb.

PMID- 30193327
TI  - Ambiguity in End-of-Life Care Terminology-What Do We Mean by "Comfort Care?"

PMID- 30193329
TI  - Novel Management of Ectopic Pregnancy in a Noncommunicating Rudimentary Horn of a
      Unicornuate Uterus.
AB  - Pregnancy in a rudimentary horn is a rarely encountered form of ectopic pregnancy
      and is often an emergent situation because of the risk of rupture of the horn. A
      31-year-old gravida 3 para 1 woman with 7 to 8 weeks' gestational age was found
      to have a viable pregnancy in a rudimentary noncommunicating horn of a
      unicornuate uterus. She elected termination of the pregnancy via local
      intracardiac lidocaine and intra-amniotic methotrexate injections. Subsequent
      removal of the rudimentary horn was necessary to prevent recurrence. Because of
      the risk of rupture, the diagnosis and management of an ectopic pregnancy in a
      rudimentary horn can be emergent.

PMID- 30193330
TI  - Jackstone Calculus.

PMID- 30193331
TI  - Necrotic Plaque on the Distal Nose With Diffuse Crateriform Nodules.

PMID- 30193325
TI  - Diagnosis and Management of Mild Traumatic Brain Injury in Children: A Systematic
      Review.
AB  - Importance: In recent years, there has been an exponential increase in the
      research guiding pediatric mild traumatic brain injury (mTBI) clinical
      management, in large part because of heightened concerns about the consequences
      of mTBI, also known as concussion, in children. The CDC National Center for
      Injury Prevention and Control's (NCIPC) Board of Scientific Counselors (BSC), a
      federal advisory committee, established the Pediatric Mild TBI Guideline
      workgroup to complete this systematic review summarizing the first 25 years of
      literature in this field of study. Objective: To conduct a systematic review of
      the pediatric mTBI literature to serve as the foundation for an evidence-based
      guideline with clinical recommendations associated with the diagnosis and
      management of pediatric mTBI. Evidence Review: Using a modified Delphi process,
      the authors selected 6 clinical questions on diagnosis, prognosis, and management
      or treatment of pediatric mTBI. Two consecutive searches were conducted on
      PubMed, Embase, ERIC, CINAHL, and SportDiscus. The first included the dates
      January 1, 1990, to November 30, 2012, and an updated search included December 1,
      2012, to July 31, 2015. The initial search was completed from December 2012 to
      January 2013; the updated search, from July 2015 to August 2015. Two authors
      worked in pairs to abstract study characteristics independently for each article
      selected for inclusion. A third author adjudicated disagreements. The risk of
      bias in each study was determined using the American Academy of Neurology
      Classification of Evidence Scheme. Conclusion statements were developed regarding
      the evidence within each clinical question, and a level of confidence in the
      evidence was assigned to each conclusion using a modified GRADE methodology. Data
      analysis was completed from October 2014 to May 2015 for the initial search and
      from November 2015 to April 2016 for the updated search. Findings: Validated
      tools are available to assist clinicians in the diagnosis and management of
      pediatric mTBI. A significant body of research exists to identify features that
      are associated with more serious TBI-associated intracranial injury, delayed
      recovery from mTBI, and long-term sequelae. However, high-quality studies of
      treatments meant to improve mTBI outcomes are currently lacking. Conclusions and
      Relevance: This systematic review was used to develop an evidence-based clinical
      guideline for the diagnosis and management of pediatric mTBI. While an increasing
      amount of research provides clinically useful information, this systematic review
      identified key gaps in diagnosis, prognosis, and management.

PMID- 30193332
TI  - Moving Toward Every Patient Training for Surgery.

PMID- 30193333
TI  - Clarification on Uveal Melanoma Associated With Myotonic Dystrophy.

PMID- 30193334
TI  - Exploring the Effects of Imitating Hand Gestures and Head Nods on L1 and L2
      Mandarin Tone Production.
AB  - Purpose: This study investigated the impact of metaphoric actions-head nods and
      hand gestures-in producing Mandarin tones for first language (L1) and second
      language (L2) speakers. Method: In 2 experiments, participants imitated videos of
      Mandarin tones produced under 3 conditions: (a) speech alone, (b) speech + head
      nods, and (c) speech + hand gestures. Fundamental frequency was recorded for both
      L1 (Experiment 1) and L2 (Experiment 2a) speakers, and the output of the L2
      speakers was rated for tonal accuracy by 7 native Mandarin judges (Experiment
      2b). Results: Experiment 1 showed that 12 L1 speakers' fundamental frequency
      spectral data did not differ among the 3 conditions. In Experiment 2a, the
      conditions did not affect the production of 24 English speakers for the most
      part, but there was some evidence that hand gestures helped Tone 4. In Experiment
      2b, native Mandarin judges found limited conditional differences in L2
      productions, with Tone 3 showing a slight head nods benefit in a subset of
      "correct" L2 tokens. Conclusion: Results suggest that metaphoric bodily actions
      do not influence the lowest levels of L1 speech production in a tonal language
      and may play a very modest role during preliminary L2 learning.

PMID- 30193336
TI  - Error in Data Presentation in Text.

PMID- 30193335
TI  - Congenital Syphilis-Still a Shadow on the Land.

PMID- 30193337
TI  - Effect of Exercise and Nutrition Prehabilitation on Functional Capacity in
      Esophagogastric Cancer Surgery: A Randomized Clinical Trial.
AB  - Importance: Preserving functional capacity is a key element in the care continuum
      for patients with esophagogastric cancer. Prehabilitation, a preoperative
      conditioning intervention aiming to optimize physical status, has not been tested
      in upper gastrointestinal surgery to date. Objective: To investigate whether
      prehabilitation is effective in improving functional status in patients
      undergoing esophagogastric cancer resection. Design, Setting, and Participants: A
      randomized clinical trial (available-case analysis based on completed
      assessments) was conducted at McGill University Health Centre (Montreal, Quebec,
      Canada) comparing prehabilitation with a control group. Intervention consisted of
      preoperative exercise and nutrition optimization. Participants were adults
      awaiting elective esophagogastric resection for cancer. The study dates were
      February 13, 2013, to February 10, 2017. Main Outcomes and Measures: The primary
      outcome was change in functional capacity, measured with absolute change in 6
      minute walk distance (6MWD). Preoperative (end of the prehabilitation period) and
      postoperative (from 4 to 8 weeks after surgery) data were compared between
      groups. Results: Sixty-eight patients were randomized, and 51 were included in
      the primary analysis. The control group were a mean (SD) age, 68.0 (11.6) years
      and 20 (80%) men. Patients in the prehabilitation group were a mean (SD) age,
      67.3 (7.4) years and 18 (69%) men. Compared with the control group, the
      prehabilitation group had improved functional capacity both before surgery (mean
      [SD] 6MWD change, 36.9 [51.4] vs -22.8 [52.5] m; P < .001) and after surgery
      (mean [SD] 6MWD change, 15.4 [65.6] vs -81.8 [87.0] m; P < .001). Conclusions and
      Relevance: Prehabilitation improves perioperative functional capacity in
      esophagogastric surgery. Keeping patients from physical and nutritional status
      decline could have a significant effect on the cancer care continuum. Trial
      Registration: ClinicalTrials.gov Identifier: NCT01666158.

PMID- 30193338
TI  - Validation of Haptic Properties of Materials for Endoscopic Sinus and Skull Base
      Surgery Simulation.

PMID- 30193339
TI  - Campaign Contributions From Political Action Committees to Members of
      Congressional Committees Responding to the Opioid Crisis.

PMID- 30193340
TI  - US Food and Drug Administration Inspection of Tobacco Sales to Minors at Top
      Pharmacies, 2012-2017.

PMID- 30193341
TI  - Academic Achievement and Drug Abuse Risk Assessed Using Instrumental Variable
      Analysis and Co-relative Designs.
AB  - Importance: Low academic achievement (AA) in childhood and adolescence is
      associated with increased substance use. Empirical evidence, using longitudinal
      epidemiologic data, may provide support for interventions to improve AA as a
      means to reduce risk of drug abuse (DA). Objective: To clarify the nature of the
      association between adolescent AA and risk of DA by using instrumental variable
      and co-relative analysis designs. Design, Setting, and Participants: This study,
      assessing nationwide data from individuals born in Sweden between 1971 and 1982,
      used instrumental variable and co-relative analyses of the association between AA
      and DA. The instrument was month of birth. Co-relative analyses were conducted in
      pairs of cousins (263 222 pairs), full siblings (154 295), and monozygotic twins
      (1623) discordant for AA, with raw results fitted to a genetic model. The AA-DA
      association was modeled using Cox regression. Data analysis was conducted from
      October 2017 to January 2018. Exposures: Academic achievement assessed at 16
      years of age (for instrumental variable analyses), and estimated discordance in
      AA in pairs of monozygotic twins (for co-relative analyses). Main Outcomes and
      Measures: Drug abuse registration in national medical, criminal, or pharmacy
      registries. Results: This instrumental variable analysis included 934 462
      participants (478 341 males and 456 121 females) with a mean (SD) age of 34.7
      (4.3) years at a mean follow-up of 19 years. Earlier month of birth was
      associated with a linear effect on AA, with the regression coefficient per month
      equaling -0.0225 SDs (95% CI, -0.0231 to -0.0219). Controlling for AA, month of
      birth had no association with risk of DA (hazard ratio [HR], 1.000; 95% CI, 0.997
      1.004). Lower AA had a significant association with risk of subsequent DA
      registration (HR per SD, 2.33; 95% CI, 2.30-2.35). Instrumental variable analysis
      produced a substantial but modestly attenuated association (HR, 2.04; 95% CI,
      1.75-2.33). Controlling for modest associations between month of birth and
      parental educational status and DA risk reduced the association to a HR of 1.92
      (95% CI, 1.67-2.22). The genetic model applied to the results of co-relative
      analyses fitted the observed data well and estimated the AA-DA association in
      monozygotic twins discordant for AA to equal a HR of 1.79 (95% CI, 1.64-1.92).
      Conclusions and Relevance: Two different methodological approaches with divergent
      assumptions both produced results consistent with the hypothesis that the
      significant association observed between AA at 16 years of age and risk of DA
      into middle adulthood may be causal. These results provide empirical support for
      efforts to improve AA as a means to reduce risk of DA.

PMID- 30193342
TI  - Pregnancy Outcomes in Women With Transposition of the Great Arteries After an
      Arterial Switch Operation.
AB  - Importance: A growing number of women are approaching childbearing age after
      arterial switch surgery for transposition of the great arteries. Prepregnancy
      counseling requires updated knowledge of the additional cardiovascular risks
      pregnancy poses for this cohort of women and the potential effect on their
      offspring; however, to our knowledge, this information is currently unknown.
      Objective: To determine the pregnancy outcomes of women with transposition of the
      great arteries after an arterial switch operation, as well as the outcomes of
      their offspring. Design, Setting, and Participants: This cohort study assessed
      women who had had arterial switch surgery from 1985 to the present and who were
      16 years or older as of January 2018. All women with a previous arterial switch
      surgery for transposition of the great arteries with completed or ongoing
      pregnancy were included. Data were collected in a level 1 congenital cardiology
      center and joint obstetrics-cardiology clinic in Birmingham, United Kingdom.
      Exposures: Patients were assessed before, during, and after pregnancy. Main
      Outcomes and Measures: Adverse maternal cardiac events (arrhythmia, heart
      failure, aortic dissection, or acute coronary syndrome) and aortic root
      dilatation, aortic regurgitation, and left ventricular function before and after
      pregnancy were the main outcomes. Mode of delivery and fetal outcomes were
      considered secondary outcomes. Results: A total of 25 pregnancies were identified
      in 15 women; 8 women had had 1 pregnancy, while 7 were multiparous. There were no
      adverse maternal cardiac events. Before pregnancy, 8 women (53%) had no aortic
      regurgitation, 1 (7%) had a trivial degree of regurgitation, 4 (26%) had mild
      regurgitation, and 2 (14%) had moderate regurgitation. After pregnancies, 1 woman
      (7%) had minor progression of aortic regurgitation. Five women (36%) had mild
      neoaortic root dilatation prepregnancy, but none developed progressive dilatation
      in the first year post-partum. A total of 24 pregnancies were completed by the
      end of the study, with all infants born alive and well. Nineteen modes of
      delivery were known; there were 7 cesarean deliveries (37%), of which 2 (11%)
      were recommended for aortic dilatation and 5 (26%) for obstetric indications or
      maternal choice. Conclusions and Relevance: Pregnancy is well tolerated after
      arterial switch operation; no adverse maternal cardiac events or early
      progression of neoaortic root dilatation or aortic regurgitation were observed in
      this study. These results provide evidence to allow reassurance of women with
      previous arterial switch surgery who are planning pregnancies.

PMID- 30193344
TI  - A two-level hierarchical framework of visual short-term memory.
AB  - Over the last couple of decades, a vast amount of research has been dedicated to
      understanding the nature and the architecture of visual short-term memory (VSTM),
      the mechanism by which currently relevant visual information is maintained.
      According to discrete-capacity models, VSTM is constrained by a limited number of
      discrete representations held simultaneously. In contrast, shared-resource models
      regard VSTM as limited in resources, which can be distributed flexibly between
      varying numbers of representations; and a new interference model posits that
      capacity is limited by interference among items. In this article, we begin by
      reviewing benchmark findings regarding the debate over VSTM limitations, focusing
      on whether VSTM storage is all-or-none and on whether object complexity affects
      capacity. After that, we put forward a hybrid framework of VSTM architecture,
      arguing that this system is composed of a two-level hierarchy of memory stores,
      each containing a different set of representations: (1) perceptual memory, a
      resourcelike level containing analog automatically formed representations of
      visual stimuli in varying degrees of activation, and (2) visual working memory,
      in which a subset of three to four items from perceptual memory are bound to
      conceptual representations and to their locations, thus conveying discrete
      (digital/symbolic) information which appears quantized. While perceptual memory
      has a large capacity and is relatively nonselective, visual working memory is
      restricted in the number of items that can be maintained simultaneously, and its
      content is regulated by a gating mechanism.

PMID- 30193346
TI  - Contrasting effects of exogenous cueing on saccades and reaches.
AB  - Previous studies have shown that eye and arm movements tend to be intrinsically
      coupled in their behavior. There is, however, no consensus on whether planning of
      eye and arm movements is based on shared or independent representations. One way
      to gain insight into these processes is to compare how exogenous attentional
      modulation influences the temporal and spatial characteristics of the eye and the
      arm during single or combined movements. Thirteen participants (M = 22.8 years
      old, SD = 1.5) performed single or combined movements to an eccentric target. A
      behaviorally irrelevant cue flashed just before the target at different
      locations. There was no effect of the cue on the saccade or reach amplitudes,
      whether they were performed alone or together. We found no differences in overall
      reaction times (RTs) between single and combined movements. With respect to the
      effect of the cue, both saccades and reaches followed a similar pattern with the
      shortest RTs when the cue was closest to the target, which we propose reflects
      effector-independent processes. Compared to when no cue was presented before the
      target, saccade RTs were generally inhibited by the irrelevant cue with
      increasing cue-target distance. In contrast, reach RTs showed strong facilitation
      at the target location and less facilitation at farther distances. We propose
      that this reflects the presence of effector-dependent processes. The similarities
      and differences in RTs between the saccades and reaches are consistent with
      effector-dependent and -independent processes working in parallel.

PMID- 30193343
TI  - Creating correct blur and its effect on accommodation.
AB  - Blur occurs naturally when the eye is focused at one distance and an object is
      presented at another distance. Computer-graphics engineers and vision scientists
      often wish to create display images that reproduce such depth-dependent blur, but
      their methods are incorrect for that purpose. They take into account the scene
      geometry, pupil size, and focal distances, but do not properly take into account
      the optical aberrations of the human eye. We developed a method that, by
      incorporating the viewer's optics, yields displayed images that produce retinal
      images close to the ones that occur in natural viewing. We concentrated on the
      effects of defocus, chromatic aberration, astigmatism, and spherical aberration
      and evaluated their effectiveness by conducting experiments in which we attempted
      to drive the eye's focusing response (accommodation) through the rendering of
      these aberrations. We found that accommodation is not driven at all by
      conventional rendering methods, but that it is driven surprisingly quickly and
      accurately by our method with defocus and chromatic aberration incorporated. We
      found some effect of astigmatism but none of spherical aberration. We discuss how
      the rendering approach can be used in vision science experiments and in the
      development of ophthalmic/optometric devices and augmented- and virtual-reality
      displays.

PMID- 30193347
TI  - Preference for People-First Language Among Patients Seeking Bariatric Surgery.

PMID- 30193345
TI  - Ensemble statistics accessed through proxies: Range heuristic and dependence on
      low-level properties in variability discrimination.
AB  - People can quickly and accurately compute not only the mean size of a set of
      items but also the size variability of the items. However, it remains unknown how
      these statistics are estimated. Here we show that neither parallel access to all
      items nor random subsampling of just a few items is sufficient to explain
      participants' estimations of size variability. In three experiments, we had
      participants compare two arrays of circles with different variability in their
      sizes. In the first two experiments, we manipulated the congruency of the range
      and variance of the arrays. The arrays with congruent range and variability
      information were judged more accurately, indicating the use of range as a proxy
      for variability. Experiments 2B and 3 showed that people also are not invariant
      to low- or mid-level visual information in the arrays, as comparing arrays with
      different low-level characteristics (filled vs. outlined circles) led to
      systematic biases. Together, these experiments indicate that range and low- or
      mid-level properties are both utilized as proxies for variability discrimination,
      and people are flexible in adopting these strategies. These strategies are at
      odds with the claim of parallel extraction of ensemble statistics per se and
      random subsampling strategies previously proposed in the literature.

PMID- 30193348
TI  - Politics and Health Care.

PMID- 30193349
TI  - Comparison of Dermatologist Density Between Urban and Rural Counties in the
      United States.
AB  - Importance: As the US population continues to increase and age, there is an unmet
      need for dermatologic care; therefore, it is important to identify and understand
      the characteristics and patterns of the dermatologist workforce. Objective: To
      analyze the longitudinal dermatologist density and urban-rural disparities using
      a standardized classification scheme. Design, Setting, and Participants: This
      study analyzed county-level data for 1995 to 2013 from the Area Health Resources
      File to evaluate the longitudinal trends and demographic and environmental
      factors associated with the geographic distribution of dermatologists. Main
      Outcomes and Measures: Active US dermatologist and physician density. Results: In
      this study of nationwide data on dermatologists, dermatologist density increased
      by 21% from 3.02 per 100 000 people to 3.65 per 100 000 people from 1995 to 2013;
      the gap between the density of dermatologists in urban and other areas increased
      from 2.63 to 3.06 in nonmetropolitan areas and from 3.41 to 4.03 in rural areas.
      The ratio of dermatologists older than 55 years to younger than 55 years
      increased 75% in nonmetropolitan and rural areas (from 0.32 to 0.56) and 170% in
      metropolitan areas (from 0.34 to 0.93). Dermatologists tended to be located in
      well-resourced, urban communities. Conclusions and Relevance: Our findings
      suggest that substantial disparities in the geographic distribution of
      dermatologists exist and have been increasing with time. Correcting the workforce
      disparity is important for patient care.

PMID- 30193350
TI  - Correlation of Central Retinal Thickness and Visual Acuity in Diabetic Macular
      Edema.

PMID- 30193351
TI  - Three Common Methodological Issues in Studies of Surgical Readmission Rates: The
      Trouble With Readmissions.

PMID- 30193352
TI  - Respectful Language and Care in Childhood Obesity.

PMID- 30193353
TI  - Evaluation of Safety and Efficacy for an Intranasal Airway Device in Nasal
      Surgery.
AB  - Importance: Postoperative packing in nasal surgery often results in nasal
      obstruction and discomfort. Commercially available silicone intranasal airways
      (IAs) serve as dual-nasal airway tubes aimed at alleviating this process, but the
      safety and efficacy of these devices are unknown. Objective: To evaluate the
      safety and efficacy of an intraoperatively placed IA device in rhinoplasty and
      nasal surgery. Design, Setting, and Participants: In this retrospective record
      review, the medical records of patients undergoing nasal surgery with insertion
      of the IA at a single institution from 2012 to 2017 were reviewed. After review
      of over 200 patients, a questionnaire was developed to assess device efficacy.
      Exposures: Use of the IA device. The IA is 12 cm long, anchored across the
      columella, extends distally along the nasal floor, and has a proximal external
      portion used for cleaning and maintaining patency. Placed intraoperatively, the
      device aims to support air flow postoperatively in the face of edema, hemorrhage,
      and packing. Results: A total of 302 operations in 300 patients were analyzed,
      including primary and revision septorhinoplasty. A total of 24 (7.9%) patients
      self-removed or inadvertently dislodged the IA. Minor acute postoperative
      complications not unique to airway insertion included cellulitis in 4 (1.3%)
      participants and epistaxis in 6 (2%). Postoperatively, 1 (0.3%) patient developed
      dehiscence along transcolumellar incisions. A total of 59 patients (100%
      compliance) completed the efficacy questionnaire. The mean breathing score was
      between good and average (2.9 of 5), comfort scores between comfortable and
      average (2.9 of 5), and mean ease of irrigation score was between very easy and
      easy (1.96 of 5). The device was irrigated on average 3.57 times per day. A total
      of 43 (76%) particpiants had full patency or only partial obstruction, compared
      with 13 (24%) patients with total obstruction. In all patients, with or without
      obstruction, the effect lasted an average of 4 days. Conclusions and Relevance:
      The device is safe and well-tolerated for maintaining patency of the nasal airway
      in patients undergoing rhinoplasty and nasal reconstruction without increased
      risk of incisional dehiscence. Level of Evidence: 4.

PMID- 30193354
TI  - Utility of Deep Learning Methods for Referability Classification of Age-Related
      Macular Degeneration.

PMID- 30193356
TI  - Understanding the Benefits of Bariatric Surgery: How Much Evidence Is Enough?

PMID- 30193355
TI  - Association of Neuroimaging Measures of Emotion Processing and Regulation Neural
      Circuitries With Symptoms of Bipolar Disorder in Offspring at Risk for Bipolar
      Disorder.
AB  - Importance: Bipolar disorder (BD) is difficult to distinguish from other
      psychiatric disorders. Neuroimaging studies can identify objective markers of BD
      risk. Objective: To identify neuroimaging measures in emotion processing and
      regulation neural circuitries and their associations with symptoms specific to
      youth at risk for BD. Design, Setting, and Participants: This cross-sectional
      (August 1, 2011, to July 31, 2017) and longitudinal (February 1, 2013, to
      November 30, 2017) neuroimaging study performed at the University of Pittsburgh
      Medical Center compared a sample of 31 offspring of parents with BD (OBP) with 28
      offspring of comparison parents with non-BD psychopathologies (OCP) and 21
      offspring of healthy parents (OHP); OBP, OCP, and OHP were recruited from the
      Bipolar Offspring Study and the Longitudinal Assessment of Manic Symptoms Study.
      Main Outcomes and Measures: Group differences in activity and functional
      connectivity during emotional face processing and n-back task performance in
      amygdala, dorsolateral and ventrolateral prefrontal cortices (PFC), caudal
      anterior cingulate cortices (cACC), and rostral anterior cingulate cortices
      (rACC) neuroimaging measures showing between-group differences and symptom
      severity (anxiety, affective lability, depression, mania). We hypothesized that
      elevated amygdala activity and/or lower PFC activity and abnormal amygdala to PFC
      functional connectivity would distinguish OBP from OCP and OHP, and magnitudes of
      these abnormalities would positively correlate with elevated symptom severity. We
      explored associations between changes in neuroimaging and symptom measures over
      follow-up (mean [SD], 2.9 [1.4] years) in a subset of participants (n = 30).
      Results: Eighty participants were included (mean [SD] age, 14.2 (2.1) years; 35
      female). Twelve neuroimaging measures explained 51% of the variance in the
      results of neuroimaging measures overall. Of the 12, 9 showed significant main
      associations of the group; however, after post hoc analyses and Bonferroni
      corrections, only 7 showed statistically significant associations between groups
      (corrected P < .05 for all). Of the 7, 2 showed significant relationships with
      symptoms. Offspring of parents with BD had greater right rACC activity when
      regulating attention to happy faces vs OCP (mean [SD] difference, 0.744 [0.249];
      95% CI, 0.134-1.354; P = .01), which positively correlated with affective
      lability severity (rho = 0.304; uncorrected P = .006). Offspring of parents with
      BD had greater amygdala to left cACC functional connectivity when regulating
      attention to fearful faces vs OCP (mean [SD] difference, 0.493 [0.169]; 95% CI,
      0.079-0.908; P = .01). Increases in this measure positively correlated with
      increases in affective lability over follow-up (r = 0.541; P = .003). Conclusions
      and Relevance: Greater anterior cingulate cortex activity and functional
      connectivity during emotion regulation tasks may be specific markers of BD risk.
      These findings highlight potential neural targets to aid earlier identification
      of and guide new treatment developments for BD.

PMID- 30193357
TI  - Trends in Visits to Acute Care Venues for Treatment of Low-Acuity Conditions in
      the United States From 2008 to 2015.
AB  - Importance: Over the past 2 decades, a variety of new care options have emerged
      for acute care, including urgent care centers, retail clinics, and telemedicine.
      Trends in the utilization of these newer care venues and the emergency department
      (ED) have not been characterized. Objective: To describe trends in visits to
      different acute care venues, including urgent care centers, retail clinics,
      telemedicine, and EDs, with a focus on visits for treatment of low-acuity
      conditions. Design, Setting, and Participants: This cohort study used
      deidentified health plan claims data from Aetna, a large, national, commercial
      health plan, from January 1, 2008, to December 31, 2015, with approximately 20
      million insured members per study year. Descriptive analysis was performed for
      health plan members younger than 65 years. Data analysis was performed from
      December 28, 2016, to February 20, 2018. Main Outcomes and Measures: Utilization,
      inflation-adjusted price, and spending associated with visits for treatment of
      low-acuity conditions. Low-acuity conditions were identified using diagnosis
      codes and included acute respiratory infections, urinary tract infections,
      rashes, and musculoskeletal strains. Results: This study included 20.6 million
      acute care visits for treatment of low-acuity conditions over the 8-year period.
      Visits to the ED for the treatment of low-acuity conditions decreased by 36%
      (from 89 visits per 1000 members in 2008 to 57 visits per 1000 members in 2015),
      whereas use of non-ED venues increased by 140% (from 54 visits per 1000 members
      in 2008 to 131 visits per 1000 members in 2015). There was an increase in visits
      to all non-ED venues: urgent care centers (119% increase, from 47 visits per 1000
      members in 2008 to 103 visits per 1000 members in 2015), retail clinics (214%
      increase, from 7 visits per 1000 members in 2008 to 22 visits per 1000 members in
      2015), and telemedicine (from 0 visits in 2008 to 6 visits per 1000 members in
      2015). Utilization and spending per person per year for low-acuity conditions had
      net increases of 31% (from 143 visits per 1000 members in 2008 to 188 visits per
      1000 members in 2015) and 14% ($70 per member in 2008 to $80 per member in 2015),
      respectively. The increase in spending was primarily driven by a 79% increase in
      price per ED visit for treatment of low-acuity conditions (from $914 per visit in
      2008 to $1637 per visit in 2015). Conclusions and Relevance: From 2008 to 2015,
      total acute care utilization for the treatment of low-acuity conditions and
      associated spending per member increased, and utilization of non-ED acute care
      venues increased rapidly. These findings suggest that patients are more likely to
      visit urgent care centers than EDs for the treatment of low-acuity conditions.

PMID- 30193359
TI  - Information Transparency in the Drug Approval Process-Reply.

PMID- 30193358
TI  - The Path to the First FDA-Approved Cannabis-Derived Treatment and What Comes
      Next.

PMID- 30193360
TI  - Predictions, Surprises, and the Future of the Dermatology Workforce.

PMID- 30193361
TI  - Perceptual Encoding in Auditory Brainstem Responses: Effects of Stimulus
      Frequency.
AB  - Purpose: A central question about auditory perception concerns how acoustic
      information is represented at different stages of processing. The auditory
      brainstem response (ABR) provides a potentially useful index of the earliest
      stages of this process. However, it is unclear how basic acoustic characteristics
      (e.g., differences in tones spanning a wide range of frequencies) are indexed by
      ABR components. This study addresses this by investigating how ABR amplitude and
      latency track stimulus frequency for tones ranging from 250 to 8000 Hz. Method:
      In a repeated-measures experimental design, listeners were presented with brief
      tones (250, 500, 1000, 2000, 4000, and 8000 Hz) in random order while
      electroencephalography was recorded. ABR latencies and amplitudes for Wave V (6-9
      ms) and in the time window following the Wave V peak (labeled as Wave VI; 9-12
      ms) were measured. Results: Wave V latency decreased with increasing frequency,
      replicating previous work. In addition, Waves V and VI amplitudes tracked
      differences in tone frequency, with a nonlinear response from 250 to 8000 Hz and
      a clear log-linear response to tones from 500 to 8000 Hz. Conclusions: Results
      demonstrate that the ABR provides a useful measure of early perceptual encoding
      for stimuli varying in frequency and that the tonotopic organization of the
      auditory system is preserved at this stage of processing for stimuli from 500 to
      8000 Hz. Such a measure may serve as a useful clinical tool for evaluating a
      listener's ability to encode specific frequencies in sounds. Supplemental
      Material: https://doi.org/10.23641/asha.6987422.

PMID- 30193362
TI  - Anatomical Features of Gray Crescent.

PMID- 30193363
TI  - Comparison of Health, Development, Maternal Bonding, and Poverty Among Children
      Born After Denial of Abortion vs After Pregnancies Subsequent to an Abortion.
AB  - Importance: Evidence indicates that there are potential health, development, and
      maternal bonding consequences for children born from unwanted pregnancies.
      Objective: To examine the association of women receiving or being denied a wanted
      abortion with their children's health and well-being. Design, Setting, and
      Participants: A 5-year longitudinal observational study with a quasi-experimental
      design conducted between January 18, 2008, and January 25, 2016, examined women
      who received abortions just under the gestational age limit of 30 abortion
      facilities across the United States and women who were denied abortion just
      beyond the gestational age limit in these facilities. Analyses compared the
      children of 146 women who were denied an abortion (index children) with children
      born to 182 women who received an abortion and had a subsequent child within 5
      years (subsequent children). Interview-to-interview retention averaged 94.5%
      (6895 of 7293) across the 11 semi-annual interviews. Exposures: Being born after
      denial of abortion vs after a new pregnancy subsequent to an abortion. Main
      Outcomes and Measures: Perinatal outcomes and child health, child development,
      maternal bonding, socioeconomics, and household structure. Results: This study
      included 328 women who had children during the study period (mean [SD] age at
      study recruitment, 23.7 [4.9] years). There were no differences by study group in
      consent to participate in the study, completion of first interview, or
      continuation in the study. Among the 328 children in the study (146 index
      children and 182 subsequent children), there were 163 girls and 165 boys.
      Perinatal and child health outcomes were not different between subsequent and
      index children, and there was no clear pattern of delayed child development.
      However, mixed-effects models adjusting for clustered recruitment and multiple
      observations per child revealed that poor maternal bonding was more common for
      index children compared with subsequent children (9% vs 3%; adjusted odds ratio,
      5.14; 95% CI, 1.48-17.85). Index children lived in households with lower incomes
      relative to the federal poverty level than did subsequent children (101% vs 132%
      of federal poverty level; adjusted regression coefficient, -0.31; 95% CI, -0.52
      to -0.10), and were more likely to live in households without enough money to pay
      for basic living expenses (72% vs 55%; adjusted odds ratio, 5.16; 95% CI, 2.34
      11.40). Conclusions and Relevance: These findings suggest that access to abortion
      enables women to choose to have children at a time when they have more financial
      and emotional resources to devote to their children.

PMID- 30193364
TI  - Sudden Unilateral Decrease in Vision in a Healthy Middle-aged Man.

PMID- 30193365
TI  - Education and Reporting of Diagnostic Errors Among Physicians in Internal
      Medicine Training Programs.

PMID- 30193367
TI  - Information Transparency in the Drug Approval Process.

PMID- 30193366
TI  - Modeling Stroke Patient Transport for All Patients With Suspected Large-Vessel
      Occlusion.
AB  - Importance: Ischemic stroke with large-vessel occlusion can be treated with
      alteplase and/or endovascular therapy; however, the administration of each
      treatment is time sensitive. Objective: To identify the optimal triage and
      transport strategy: direct to the endovascular center (mothership) or immediate
      alteplase treatment followed by transfer to the endovascular center (drip and
      ship), for all patients with suspected large-vessel occlusion stroke. Design
      Setting, and Participants: This was a theoretical, conditional probability
      modeling study. Existing data from clinical trials of stroke treatment were used
      for model generation. The study was conducted from February 1, 2017, to March 1,
      2018. Main Outcomes and Measures: The time-dependent efficacy of alteplase and
      endovascular therapy and the accuracy of large-vessel occlusion screening tools
      were modeled to estimate the probability of positive outcome (modified Rankin
      Scale score, 0-1 at 90 days) for both the drip-and-ship and mothership transport
      strategies. Based from onset to treatment, the strategy that estimates the
      greatest probability of excellent outcome is determined in several different
      scenarios. Results: The patient's travel time from both thrombolysis and
      endovascular therapy centers, speed of treatment, and positive predictive value
      of the screening tool affect whether the drip-and-ship or mothership strategy
      estimates best outcomes. With optimal treatment times (door-to-needle time: 30
      minutes; door-in-door-out time: 50 minutes; door-to-groin-puncture time: 60
      minutes [mothership], 30 minutes [drip and ship]), both options estimate similar
      outcomes when the centers are 60 minutes or less apart. However, with increasing
      travel time between the 2 centers (90 or 120 minutes), drip and ship is favored
      if the patient would have to travel past the thrombolysis center to reach the
      endovascular therapy center or if the patient would arrive outside the alteplase
      treatment time window in the mothership scenario. Holding other variables
      constant, if treatment times are slow at the thrombolysis center (door-to-needle
      time: 60 minutes; door-in-door-out time: 120 minutes), the area where mothership
      estimates the best outcomes expands, especially when the 2 centers are close
      together (60 minutes apart or less). The area where mothership estimates the best
      outcome also expands as the positive predictive value of the screening tool
      increases. Conclusions and Relevance: This study suggests that decision making
      for prehospital transport can be modeled using existing clinical trial data and
      that these models can be dynamically adapted to changing realities. Based on
      current median treatment times to realize the full benefit of endovascular
      therapy on a population level, the study findings suggest that delivery of the
      treatment should be regionally centralized. The study modeling suggests that
      transport decision making is context specific and the radius of superiority of
      the transport strategy changes based on treatment times at both centers,
      transport times, and the triaging tool used.

PMID- 30193369
TI  - Erratum.

PMID- 30193370
TI  - Clinician Burnout and the Quality of Care.

PMID- 30193368
TI  - Association of Cognition and Age-Related Hearing Impairment in the English
      Longitudinal Study of Ageing.
AB  - Importance: Evidence has linked age-related hearing impairment (ARHI) with
      cognitive decline; however, very few studies (none in the United Kingdom) explore
      this link in large well-characterized groups of community-dwelling individuals.
      Objective: To investigate the link between ARHI and cognitive decline using a
      cohort of elderly individuals from the United Kingdom and explore untreated
      hearing loss and social isolation as potential explanations for the observed
      link. Design, Setting, and Participants: This cross-sectional analysis of wave 7
      (June 2014 through May 2015) of the English Longitudinal Study of Ageing (ELSA)
      sampled men and women 50 years or older and living in the United Kingdom in a
      community setting. Those with a diagnosis of dementia, Alzheimer disease, or
      Parkinson disease or with ear infections and cochlear implants were excluded.
      Data were analyzed from August 1, 2017, through May 25, 2018. Main Outcomes and
      Measures: Memory and executive function as measures of cognitive function and
      hearing acuity derived from the HearCheck screener device (Siemens). Results: Of
      a cohort of 9666 members in wave 7 of ELSA, 7385 were eligible for analysis after
      applying exclusion criteria (55.1% women; mean [SD] age, 67.4 [9.4] years). Of
      these, 3056 (41.4%) had mild hearing loss and 755 (10.2%) had severe hearing
      loss; 834 (11.3%) used a hearing aid; and 7155 (96.9%) were white. Hearing loss
      had a negative association with cognition; for those with moderate to severe
      loss, the score on memory assessment was a full 1 point less (-1.00; 95% CI, 
      1.24 to -0.76), ceteris paribus, relative to those with no hearing loss. However,
      this association was seen only in the individuals with untreated hearing loss
      (ie, those who did not use hearing aids) (-1.16; 95% CI, -1.45 to -0.87).
      Evidence suggests that social isolation acts as a mediating factor. Conclusions
      and Relevance: Although hearing loss and cognition are linked, untreated hearing
      loss drives the association. Social isolation is a mediating factor in the link
      for those who have untreated hearing loss. Cognitive decline associated with ARHI
      is probably preventable by early rehabilitation and increased opportunistic
      screening for the elderly.

PMID- 30193371
TI  - Error in Results.

PMID- 30193374
TI  - Laser Treatment Performed More Than 4 Decades After Napalm Burns: Healing the
      Scars of the "Napalm Girl".

PMID- 30193375
TI  - Association of Low Nodal Positivity Rate Among Patients With ERBB2-Positive or
      Triple-Negative Breast Cancer and Breast Pathologic Complete Response to
      Neoadjuvant Chemotherapy.
AB  - Importance: A recent publication reported that of 527 patients with clinically
      node-negative (cN0) cT1/cT2 triple-negative breast cancer (TNBC) or ERBB2
      positive disease treated with neoadjuvant chemotherapy (NAC), 100% of those who
      achieved a breast pathologic complete response (pCR) had pathologic node
      negativity (pN0). Eliminating axillary surgery in these patients has been
      suggested as safe based on these results. Objective: To evaluate nodal positivity
      rates in patients with cT1/cT2 N0 ERBB2-positive disease and TNBC with a breast
      pCR after NAC using the National Cancer Database (NCDB), which included academic
      and community settings. Design, Setting, and Participants: This retrospective
      study reviewed data from the NCDB from January 1, 2010, through December 31,
      2015. Participants included patients with cN0/cN1 cT1/cT2 breast cancer who
      received NAC followed by surgery. Pathologic nodal positivity rates by breast pCR
      were compared in cN0 and cN1 disease, within each tumor subtype (ERBB2-positive,
      TNBC, and hormone receptor-positive/ERBB2-negative). Data were analyzed from
      September 13, 2017, through January 30, 2018. Exposures: Neoadjuvant chemotherapy
      followed by surgery. Main Outcomes and Measures: The pathologic nodal positivity
      rate after NAC (ypN) specifically in patients with cT1/cT2 cN0 ERBB2-positive
      disease or TNBC who achieve a breast pCR after NAC. Results: A total of 30 821
      patients with cT1/cT2 cN0/cN1 breast cancer treated with NAC and surgical
      resection (99.6% female; mean [SD] age, 52.0 [11.5] years) were identified. Of
      6802 patients with cN0 ERBB2-positive disease, 3062 (45.0%) achieved breast pCR
      and of those, 49 (1.6%; 95% CI, 1.2%-2.1%) were ypN positive. In 6222 patients
      with cN0 TNBC, 2315 (37.2%) achieved breast pCR, and of those, 36 (1.6%; 95% CI,
      1.1%-2.1%) were pathologic node positive after NAC. Rates of ypN positivity were
      higher in patients with cN0 and residual disease in the breast; 632 of 3740
      (16.9%) with ERBB2-positive disease and 492 of 3907 (12.6%) with TNBC with
      residual disease in the breast were node positive (P < .001). Among 4164 patients
      with cN1 ERBB2-positive disease, 1801 (43.3%) achieved breast pCR, with 223 of
      those (12.4%) being ypN positive. In 3293 patients with TNBC, 1229 (37.3%)
      achieved breast pCR, with 173 of these (14.1%) being ypN postive. Breast pCR
      rates were lower in hormone receptor-positive/ERBB2-negative disease (646 of 5069
      [12.7%] for cN0; 711 of 5271 [13.5%] for cN1) and ypN positivity rates were 26 of
      646 (4.0%) in cN0 vs 217 of 711 (30.5%) in cN1 disease with breast pCR and 1464
      of 4423 (33.1%) in cN0 disease vs 3775 of 4560 (82.8%) in cN1 disease with
      residual disease in the breast. Conclusions and Relevance: In this study, the
      highest rates of breast pCR were seen in ERBB2-positive disease and TNBC. In
      patients with cN0 ERBB2-positive disease or TNBC with breast pCR, the nodal
      positivity rate was less than 2%, which supports consideration of omission of
      axillary surgery in this subset of patients.

PMID- 30193376
TI  - Clarification on Uveal Melanoma Associated With Myotonic Dystrophy-Reply.

PMID- 30193378
TI  - Pediatric Computed Tomography Scans and Cancer Risk-Reply.

PMID- 30193377
TI  - Substantial Shifts in Supreme Court Health Law Jurisprudence.

PMID- 30193379
TI  - Disparities in Low-Vision Device Use Among Older US Medicare Recipients.
AB  - Importance: Low-vision assistive devices are not covered by Medicare and many
      private insurers, although there is evidence that they can improve functioning
      and quality of life. Little is known about whether sociodemographic disparities
      exist in the use of low-vision services by Medicare beneficiaries. Objective: To
      determine if sociodemographic disparities exist in the use of low-vision services
      by Medicare beneficiaries. Design, Setting, and Participants: Cross-sectional
      population-based survey. The National Health Interview Survey is an annually
      administered nationally representative US survey. Data used in this study were
      from the 2002, 2008, and 2016 National Health Interview Survey vision supplement.
      Participants who were Medicare beneficiaries 65 years and older with self
      reported vision impairment were included. Main Outcomes and Measures:
      Multivariable logistic regression was performed to evaluate if sociodemographic
      or economic factors were associated with self-reported use of low-vision devices
      or low-vision rehabilitation among Medicare beneficiaries 65 years and older who
      self-reported vision impairment. Results: There were 3058 participants included
      in the study. The survey weighted proportion of participants who were men was
      37.9% (95% CI, 35.8%-40.0%), while 79.1% (95% CI, 77.2%-80.9%) were non-Hispanic
      white, 10.2% (95% CI, 9.0%-11.5%) were non-Hispanic black, 6.7% (95% CI, 5.6%
      8.1%) were Hispanic, and 4.0% (95% CI, 3.2%-5.0%) identified with another
      race/ethnicity. The weighted proportion who reported using low-vison devices and
      low-vision rehabilitation were 26.1% (95% CI, 24.2%-28.1%) and 3.5% (95% CI, 2.8%
      4.3%), respectively. In a model adjusted for ocular diagnoses, Hispanic
      individuals (odds ratio, 0.61; 95% CI, 0.39-0.97) and individuals from other
      races/ethnicities (odds ratio, 0.39; 95% CI, 0.19-0.80), but not black
      individuals, were significantly less likely to report using low-vision devices
      than white individuals. In the model that was not adjusted for ocular diagnoses,
      black individuals (odds ratio, 0.73; 95% CI, 0.54-0.99) were also significantly
      less likely to report using low-vision devices. There were no significant
      racial/ethnic disparities for reported use of low-vision rehabilitation.
      Conclusions and Relevance: Additional research is needed to clarify the
      association between sociodemographics and use of low-vision services in the
      Medicare population. However, policy makers could consider expanding Medicare
      coverage to include low-vision devices in an effort to address significant
      disparities in the use of this evidence-based intervention.

PMID- 30193380
TI  - Interpregnancy Body Mass Index Changes: Distribution and Impact on Adverse
      Pregnancy Outcomes in the Subsequent Pregnancy.
AB  - OBJECTIVE:  To examine the change in body mass index (BMI) categories between
      pregnancies and its effect on adverse pregnancy outcomes. STUDY DESIGN:  We
      performed a retrospective cohort study of women with two consecutive deliveries
      from 2005 to 2010. Analysis was limited to women with BMI recorded at <24 weeks
      for both pregnancies. Standard BMI categories were used. Adverse pregnancy
      outcomes included preterm birth at <37 weeks, intrauterine growth restriction
      (IUGR), pregnancy-related hypertension, and gestational diabetes mellitus (GDM).
      Women with increased BMI category between pregnancies were compared with those
      who remained in the same BMI category. RESULTS:  In total, 537 women were
      included, of whom 125 (23%) increased BMI category. There was no association
      between increase in BMI category and risk of preterm birth, IUGR, or pregnancy
      related hypertension. Women who increased BMI category had an increased odds of
      GDM compared with women who remained in the same BMI category (6.4 vs. 2.2%; p =
      0.018). The increased risk remained after controlling for age, history of GDM,
      and starting BMI (adjusted odds ratio: 8.2; 95% confidence interval: 2.1-32.7; p
      = 0.003). CONCLUSION:  Almost one-quarter of women increased BMI categories
      between pregnancies. This modifiable risk factor has a significant impact on the
      risk of GDM.

PMID- 30193381
TI  - Cord Blood Erythropoietin and Hepcidin Reflect Lower Newborn Iron Stores due to
      Maternal Obesity during Pregnancy.
AB  - OBJECTIVE:  Obesity during pregnancy impedes fetal iron endowment. In adults,
      both iron depletion and hypoxia stimulate erythropoietin (Epo) production, while
      hepcidin, the primary iron regulator, is inhibited by Epo and stimulated by
      obesity. To understand this relationship in fetuses, we investigated obesity,
      inflammation, and fetal iron status on fetal Epo and hepcidin levels. STUDY
      DESIGN:  Epo, hepcidin, C-reactive protein (CRP), and ferritin levels were
      measured in 201 newborns of 35 to 40 weeks' gestation with historical risk
      factors for a low fetal iron endowment, including half with maternal obesity.
      RESULTS:  Epo was unrelated to fetal size, but Epo was directly related to
      maternal body mass index (BMI; kg/m2) (p < 0.03) and CRP (p < 0.0005) at
      delivery. Epo levels were twice as likely to be elevated (>=50 IU/L) while
      comparing the lowest quartile of ferritin with the upper three quartiles (p <
      0.01). Hepcidin was directly related to ferritin (p < 0.001) and indirectly
      related to maternal BMI (p < 0.015), but BMI became nonsignificant when
      undergoing multivariate analysis. Hepcidin was unrelated to Epo. CONCLUSION: 
      Although some of the fetal responses involving Epo were similar to adults, we did
      not find a hepcidin-Epo relationship like that of adults, where fetal liver is
      the site of both hepcidin and Epo production.

PMID- 30193383
TI  - The Difference in Sibling Birthweight and Neonatal Death: A Population-Based
      Cohort Study.
AB  - BACKGROUND:  There has been a call for customized rather than population-based
      birthweight standards that would classify smallness based on an infant's own
      growth potential. Thus, this study aimed to examine the association between the
      difference in sibling birthweight and the likelihood of neonatal death among
      second births in a U.S. POPULATION:  METHODS:  This was a population-based cohort
      study including 179,300 women who delivered their first two nonanomalous
      singleton live births in Missouri (1989-2005). We performed binary logistic
      regression to evaluate the association between being relatively smaller than the
      elder full- or half-sibling (i.e., smaller by at least 500 g) and neonatal death
      (i.e., deaths in the first 28 days of life) among second births after controlling
      for sociodemographic and pregnancy-related variables in the second pregnancy.
      RESULTS:  The adjusted odds of neonatal death were 2.54-times higher among second
      births who were relatively smaller than their elder sibling. Among relatively
      small second births, every 100-g increase in the difference in sibling
      birthweight was associated with a 13% increase in the odds of neonatal death.
      CONCLUSION:  The deviation from the elder sibling's birthweight predicts neonatal
      death. Taking into consideration the elder sibling's birthweight may be warranted
      in clinical and research settings.

PMID- 30193382
TI  - Increased Frequency of Skin-to-Skin Contact Is Associated with Enhanced Vagal
      Tone and Improved Health Outcomes in Preterm Neonates.
AB  - OBJECTIVE:  An estimation of the individual's ability to cope to environmental
      adversity, that is, stress resiliency, can be extrapolated by measuring cardiac
      vagal tone, that is, high-frequency heart rate variability (HF-HRV); indeed,
      higher HF-HRV is associated with health and developmental advantages for preterm
      neonates. Previous studies show skin-to-skin contact (SSC) improves stress
      resiliency; however, linkages between SSC and HF-HRV on outcomes have not been
      assessed. We aimed to test the hypothesis that increased SSC frequency would
      enhance HF-HRV, reduce neonatal morbidity, and improve developmental outcomes.
      STUDY DESIGN:  Weekly electrocardiograms and clinical data were obtained from 101
      preterm neonates. SSC frequency was determined from the electronic medical
      record. RESULTS:  At postnatal week 1, frequency of SSC and HF-HRV were
      positively correlated (p =.02); further, multiple stepwise regressions showed
      higher HF-HRV and SSC predicted reduced days on ventilation and oxygen, and
      shorter hospital stay (p < 0.001). Higher HF-HRV predicted lower postmenstrual
      age (PMA) at discharge (p < 0.01). CONCLUSION:  Higher SSC frequency was
      associated with increased HF-HRV during the first postnatal week. SSC and HF-HRV
      uniquely predicted diminished neonatal morbidity throughout hospitalization.
      Additionally, HF-HRV uniquely predicted earlier PMA at discharge. Augmenting SSC
      early in life enhances stress resiliency and improves health outcomes.

PMID- 30193384
TI  - Clinical Diagnosis of Placenta Accreta and Clinicopathological Outcomes.
AB  - OBJECTIVE:  To investigate the association between the intraoperative diagnosis
      of placenta accreta at the time of cesarean hysterectomy and pathological
      diagnosis. STUDY DESIGN:  This is a retrospective cohort study of all patients
      undergoing cesarean hysterectomy for suspected placenta accreta from 2000 to 2016
      at Barnes-Jewish Hospital. The primary outcome was the presence of invasive
      placentation on the pathology report. We estimated predictive characteristics of
      clinical diagnosis of placenta accreta using pathological diagnosis as the
      correct diagnosis. RESULTS:  There were 50 cesarean hysterectomies performed for
      suspected abnormal placentation from 2000 to 2016. Of these, 34 (68%) had a
      diagnosis of accreta preoperatively and 16 (32%) were diagnosed intraoperatively
      at the time of cesarean delivery. Two patients had no pathological evidence of
      invasion, corresponding to a false-positive rate of 4% (95% confidence interval
      [CI]: 0.5%, 13.8%) and a positive predictive value of 96% (95% CI: 86.3%, 99.5%).
      There were no differences in complications among patients diagnosed
      intraoperatively compared with those diagnosed preoperatively. CONCLUSION:  Most
      patients undergoing cesarean hysterectomy for placenta accreta do have this
      diagnosis confirmed on pathology. However, since the diagnosis of placenta
      accreta was made intraoperatively in nearly a third of cesarean hysterectomies,
      intraoperative vigilance is required as the need for cesarean hysterectomy may
      not be anticipated preoperatively.

PMID- 30193385
TI  - Long-Term Effect of Lactation on Maternal Cardiovascular Function and Adiposity
      in a Murine Model.
AB  - OBJECTIVE:  Epidemiological studies suggest that lactation is associated with
      long-term maternal health benefits. To avoid confounders in human studies, we
      used a previously characterized murine model to investigate the long-term effect
      of lactation on both cardiovascular function and adiposity. STUDY DESIGN:  After
      the delivery of the pups, CD-1 female mice were randomly divided into two groups:
      lactated and nonlactated (NL). Before pregnancy and at 9 months postdelivery,
      blood pressure was measured using a tail cuff, visceral adipose tissue (VAT) and
      subcutaneous adipose tissue (SAT) were assessed by computed tomography (CT),
      echocardiography was performed using microultrasound, and cholesterol panels and
      fasting blood glucose were measured. The data were analyzed using Student's t
      test (significance at p < 0.05). RESULTS:  There were no differences in baseline
      parameters between the two groups. At 9 months postdelivery, the NL group weighed
      significantly more (p = 0.03) and demonstrated a significantly lower cardiac
      output (p = 0.05) and ejection fraction (p = 0.03). The mice in the NL group also
      had higher VAT (p < 0.01) and SAT percentiles (p = 0.03). Fasting glucose (p =
      0.01) and low-density lipoprotein (p = 0.01) were significantly higher in the NL
      group at 9 months. CONCLUSION:  Our results show the benefit of lactation is not
      just limited to the immediate postpartum period but it also extends into midlife
      in a murine model.

PMID- 30193386
TI  - Anterior Cruciate Ligament Reconstruction Using Bone-Patellar Tendon-Bone
      Autograft with Remnant Preservation: Comparison of Outcomes According to the
      Amount of Remnant Tissue.
AB  - There has been controversy about whether remnant tissue of anterior cruciate
      ligament (ACL) has to be preserved in ACL reconstruction. The purpose of the
      study was to compare clinical outcomes between groups of patients who underwent
      ACL reconstruction with bone-patellar tendon-bone (BPTB) autograft divided
      according to amount of ACL remnant and investigate effect of remnant preservation
      on outcomes of ACL reconstruction. A total of 185 patients who underwent ACL
      reconstruction with BPTB autograft were retrospectively reviewed. Patients were
      divided into four groups according to proportion of length of remnant tissue of
      injured ACL covering part of reconstructed ACL to total length of reconstructed
      ACL: group A included 83 patients with no remnant, group B consisted of 38
      patients with remnant of < 1/3, group C consisted of 35 patients with remnant of
      1/3 to2/3, and group D consisted of 29 patients with remnant of > 2/3. Primary
      outcome was International Knee Documentation Committee (IKDC) subjective score.
      Secondary outcomes were stability, range of motion, patient-reported outcomes
      determined by Lysholm knee scoring scale and Tegner activity scale, IKDC
      objective grade, and single hop for distance. Return to activity and near-return
      to activity were investigated. A minimum follow-up duration was 24 months. There
      was no statistically significant difference between four groups regarding
      postoperative anterior translation (p = 0.731), Lysholm knee score (p = 0.599),
      IKDC objective grade (p > 0.999), hop test (p = 0.878), and near-return to
      activity (p = 0.193). However, patients of group D had significantly better
      outcomes in IKDC subjective score (group A = 85.0 +/- 5.9, group B = 84.9 +/-
      8.1, group C = 87.4 +/- 6.4, group D = 89.2 +/- 8.1, p = 0.017), Tegner activity
      scale (group A = 5.0 +/- 1.1, group B = 5.2 +/- 1.0, group C = 5.7 +/- 1.3, group
      D = 5.9 +/- 1.0, p = 0.001), and return to activity (group A = 25.3%, group B =
      31.6%, group C = 45.7%, group D = 55.2%, p = 0.014). ACL reconstruction using
      BPTB autograft with remnant preservation did not provide better anterior
      stability compared with conventional ACL reconstruction. However, preservation of
      remnant of > 2/3 led to more improved activity-related clinical outcomes than no
      remnant preservation. In cases with substantial remnant tissue of injured ACL
      remaining, reconstruction of ACL while preserving as much remnant tissue as
      possible is recommended. This is a Level III, retrospective comparative
      therapeutic study.

PMID- 30193387
TI  - Similar Outcomes of Two-Stage Revisions for Infection and One-Stage Revisions for
      Aseptic Revisions of Knee Endoprostheses.
AB  - Two-stage revision knee arthroplasty using an antibiotic-loaded spacer is the
      most widely performed procedure for infected knee arthroplasties. The clinical
      outcome of this type of surgery compared with aseptic joint revision with
      exchange of tibial and femoral components is still controversial. Therefore, we
      analyzed clinical outcomes of septic two-stage revisions compared with aseptic
      one-stage revision total knee arthroplasties (TKAs). In a retrospective study, we
      assessed 135 consecutive patients who underwent two-stage revision for septic TKA
      (52 patients) and one-stage aseptic total knee revision arthroplasty (83
      patients). The average follow-up was 26.1 months for the aseptic group and 26.5
      months for the septic group. For clinical evaluation, we used the Knee Society
      Score, Oxford Knee Score, Kujala score, Turba score, and the Short Form 36 (SF
      36). Postoperative pain level was determined using the visual analog pain scale.
      The surgeries were performed 51 months (aseptic group) and 24 months (septic
      group) after primary TKA on average. The main indications for aseptic revision
      surgeries were instability (40%), aseptic loosening (22.4%), anterior knee pain
      due to pathologies of the patella (11.8%), or material wear (5.9%). In the
      clinical outcome, patients achieved 124.8 points in the aseptic group and 105.4
      points in the septic group in the Knee Society Score. The Oxford Knee Score
      revealed 29.9 points for the aseptic group and 33.9 points for the septic group.
      For the Kujala score, we found 53.2 points in the aseptic group and 48.5 points
      in the septic group. For the Turba score, we found 8.4 points in the aseptic
      group and 10.8 points in the septic group. The SF-36 (psychical) showed 52.2
      versus 49.5 points and the SF-36 (physical) showed 36.5 versus 35.4 points. Mean
      level of persisting pain on the visual analog scale was 3.0 (aseptic group) and
      3.5 (septic group). Performing septic two-stage or aseptic one-stage tibial and
      femoral revision knee arthroplasty showed similar clinical outcomes in relation
      to objective and subjective outcome measures.

PMID- 30193388
TI  - Neutral or Natural? Functional Impact of the Coronal Alignment in Total Knee
      Arthroplasty.
AB  - Total knee arthroplasty (TKA) is a very successful procedure. The alignment in
      TKA has been identified as being of importance to prevent early implant failure
      and patient dissatisfaction. Our hypothesis was that patients with a preoperative
      varus deformation remaining in a slight varus alignment as their natural
      alignment after TKA will have superior clinical results compared with patients
      who are restored in neutral alignment. A total of 115 patients were corrected
      from varus to neutral (varus-neutral) and in 33 patients a preoperative varus
      alignment was kept in varus (varus). Standardized preoperative and postoperative
      full-length hip-knee-ankle radiographs under full weight-bearing conditions were
      performed in all patients. The patients' knees were categorized preoperatively
      and postoperatively based on the angle between mechanical femoral axis and
      mechanical tibial axis. Knees with alignment between +/- 3 degrees were
      categorized as neutrally aligned, whereas alignment within <= -3 degrees was
      categorized as varus. The Knee Injury Osteoarthritis Outcome Score (KOOS) and
      Oxford Knee Score were determined retrospectively. The varus group scored
      significantly better in total KOOS (p < 0.05) compared with the varus-neutral
      group. Also, a trend was visible in the Oxford Knee Score but this was not
      significant (p > 0.05). This trend was even more evident in varus knees which
      were slightly undercorrected. The results support the assumption that leaving a
      residual varus alignment after TKA leads to better functional outcomes in TKA for
      patients with preoperative varus osteoarthritis.

PMID- 30193389
TI  - Incidence of Drug Abuse in Revision Total Knee Arthroplasty Population.
AB  - Substance abuse can have strong negative impacts on surgical outcomes. Therefore,
      this study assessed the effects of drug abuse in total knee arthroplasty (TKA)
      patients. Specifically, we identified revision TKA (RTKA): (1) incidence, (2)
      causes, (3) time to revision, and (4) patient demographics in patients with a
      history of drug abuse. The Medicare database within the PearlDiver Supercomputer
      (Warsaw, IN) was queried to identify 2,159,221 TKAs performed between 2005 and
      2012. Drug abuse was subdivided into cocaine, cannabis, opioids,
      sedatives/hypnotics/anxiolytics (SHA), amphetamines, and alcohol abusers. The
      effect of drug use on the incidence and cause for RTKA, time to revision, as well
      as patient demographics were correlated using multivariate, analysis of variance,
      and regression analyses. There was a significant increase in the number of
      primary TKAs in cocaine (p = 0.011), cannabis (p < 0.001), opioid (p < 0.001),
      SHA (p < 0.001), amphetamine (p < 0.001), and alcohol (p < 0.001) users.
      Amphetamine users had the fastest mean time to revision (691 days, standard
      deviation: 679 days). At 30-, 90-day, and 6-month postoperative, cocaine had the
      highest proportion of patients requiring RTKA (7, 12, and 20%, respectively), and
      at 1-year alcohol abusers (38%, p < 0.001). Infection was the most common cause
      of revision in all drug abuse/dependent cohorts. Age distributions varied
      significantly by group for primary TKA (p < 0.001). Comorbidity status was
      similar in all RTKA patients as determined by comparison of the mean Charlson
      comorbidity index scores (p = 0.091). Based on these results, drug abuse patients
      are at increased risk for RTKA. These high-risk patients should, therefore, be
      appropriately risk stratified and receive comprehensive postoperative pain
      management.

PMID- 30193390
TI  - Coronary Artery Bypass Grafting using Bilateral Internal Thoracic Arteries
      through a Left-Sided Minithoracotomy: A Single-Center Starting Experience.
AB  - OBJECTIVE:  Coronary artery bypass grafting (CABG) using bilateral internal
      thoracic artery (BITA) is associated with the best long-term survival. However,
      using BITA increases the risk of sternal wound infections with conventional
      sternotomy. We describe here our initial results of minimally invasive CABG (MICS
      CABG) using BITA. METHODS:  Patients were operated through an incision similar to
      that of standard minimally invasive direct CABG. All operations were performed
      off-pump. We evaluated patient's quality of life (QoL) using the Medical Outcomes
      trust, 36-Item Short Form Health Survey (SF-36). RESULTS:  Between February 2016
      and August 2017, we performed 21 cases of MICS-CABG using BITA. There was no
      intraoperative complication and no conversion to sternotomy or to on-pump. Two
      patients required reexploration through the same minithoracotomy for
      postoperative bleeding. Two cases of early postoperative graft failure were
      identified. There was no stroke or in-hospital mortality. The median duration of
      follow-up was 13 months, with a maximum of 19 months. Relief of angina was
      achieved in all patients. There was one readmission for superficial wound
      infection, which was conservatively treated. An 84-year-old man died 4 months
      after the operation. The remaining 20 patients attested good QoL with the SF-36
      questionnaire. CONCLUSIONS:  Myocardial revascularization using BITA can be
      safely achieved off-pump through a left-sided minithoracotomy with good
      postoperative and short-term outcomes.

PMID- 30193391
TI  - Synthesis and Biological Evaluation of Novel 5-Oxo-1-Phenylpyrrolidine-3
      Carboxylic Acid Analogs.
AB  - A number of 5-oxo-1-phenyl-4-(substituted methyl) pyrrolidine-3-carboxylic acid
      derivatives bearing pyrrolidine ring and methylamino residues in their structure
      were synthesized as potential antibacterial drugs. The chemical structures of all
      the compounds were established by their UV-Vis absorption spectroscopy, IR, 1H,
      13C NMR and mass spectroscopy. The in vitro antibacterial screening of all novel
      compounds was done against gram-positive Staphylococcus aureus, Bacillus subtilis
      and gram-negative Pseudomonas aeruginosa. The results revealed that compounds 5d,
      e, f and g showed moderate to good activity against the tested microbes.

PMID- 30193392
TI  - Determination of Tofacitinib in Mice Whole Blood on Dried Blood Spots Using LC
      ESI-MS/MS: Application to Pharmacokinetic Study in Mice.
AB  - A simple, sensitive and rapid assay method has been developed and validated as
      per regulatory guideline for the estimation of tofacitinib on mice dried blood
      spots (DBS) using liquid chromatography coupled to tandem mass spectrometry with
      electro spray ionization in the positive-ion mode. The method employs liquid
      extraction of tofacitinib from DBS disk of mice whole blood followed by
      chromatographic separation using 5 mM ammonium acetate (pH 6.5):acetonitrile
      (20:80, v/v) at a flow rate of 0.60 mL/min on an X-Terra Phenyl column with a
      total run time 2.5 min. The MS/MS ion transitions monitored were m/z 313->149 for
      tofacitinib and m/z 316->149 for the internal standard (13C3,15N-tofacitinib).
      The assay was linear in the range of 0.99-1980 ng/mL. The intra- and inter-day
      precision was in the range of 1.17-10.3 and 3.37-10.9%, respectively. Stability
      studies showed that tofacitinib was stable on DBS cards for one month. This novel
      method has been applied to analyze the DBS samples of tofacitinib obtained from a
      pharmacokinetic study in mice.

PMID- 30193394
TI  - The Association between Genetic Polymorphisms and Simvastatin-Induced Myopathy: A
      Narrative Synthesis of Evidence.
AB  - BACKGROUND AND STUDY AIM: Genetic polymorphisms may play a role in muscular
      injury associated with simvastatin, but results were inconclusive. This study
      aimed to summarize evidence from the literature investigating the effects of
      genetic polymorphism on simvastatin-induced myopathy. METHODS: Studies regarding
      the association between genetic polymorphisms and simvastatin-induced myopathy
      were retrieved through electronic databases from February 1, 1990 to March 15,
      2018. Two authors independently extracted data, including PMID, author,
      publication year, country, race, age, population characteristics, drugs,
      definition of case and control, gene, allele, SNP position, Hardy-Weinberg
      equilibrium, number of genotypes (case and control), minor allele frequency of
      cases and controls, association, study type and the Newcastle-Ottawa scale. Due
      to high heterogeneity in study design and outcome measurements among the included
      articles, a narrative synthesis of the evidence was conducted. RESULTS: A total
      of 10 association studies were identified in this study, including SLCO1B1,
      ABCB1, GATM, HTR3B, HTR7, RYR2 and HLA-DRB1. The evidence linking myopathy to
      rs4149056 in SLCO1B1 is of high quality, and this association has been reproduced
      in randomized trials and clinical practice-based cohorts. As for other candidate
      genetic markers, the evidences are limited or controversial, and additional well
      designed studies with larger sample sizes, are required to further elucidate this
      association. CONCLUSION: SLCO1B1 genotype is a useful biomarker for predicting an
      increased risk of simvastatin-induced myopathy.

PMID- 30193395
TI  - Lysimachia Capillipes Inhibit Adipogenesis via Angiogenesis Inhibition.
AB  - Obesity is a common and increasingly prevalent human condition due to unhealthy
      diet and less-exercise lifestyle. Development of obesity is associated with
      substantial modulation of adipose tissue structure. The expansion of adipose
      tissue is linked to the development of its vasculature, and modulation of
      angiogenesis may have the potential to impair adipose tissue development. In this
      study, we used obesity model of zebrafish fed by egg yolk to investigate the
      effect of Lysimachia capillipes on the obesity. The results showed that
      Lysimachia capillipes inhibited angiogenesis of adipose tissue in transgenic
      zebrafish Tg (Fli 1: EGFP), which was similar to surppressing effect of TNP-470,
      which was accompanied by decreased Oil Red O staining of the zebrafish. The
      treatment of Lysimachia capillipes reduced expression of MTP significantly, but
      modestly reduced expression of Ppar g, FABP10a, and CD36 level through ISH, which
      was accordant with the results by PCR analysis. The study proved that Lysimachia
      capillipes might possess novel therapeutic properties for prevention and
      treatment of obesity.

PMID- 30193393
TI  - A Single Institution Retrospective Study of the Clinical Efficacy of Tiotropium
      Respimat in Never-Smoking Elderly Asthmatics with Irreversible Airflow
      Limitation.
AB  - OBJECTIVE: In Japan, most asthma deaths occur among the elderly. We should
      improve the control of asthma in elderly patients to reduce the number of deaths
      due to asthma. This retrospective study aimed to evaluate the efficacy of
      tiotropium RespimatR (Tio-Res) in symptomatic, never-smoking, elderly asthmatics
      with irreversible airflow limitation despite the use of high-dose inhaled
      corticosteroids (ICS) plus long-acting beta2-adrenoceptor agonists (LABA).
      METHODS: The Asthma Control TestTM (ACT), pulmonary function tests, morning and
      evening peak flow (mPEF, ePEF, respectively, evaluated with an ASSESS(r) peak
      flow meter), and respiratory impedance (assessed with MostGraph(r)) were measured
      before and after a minimum of one year of Tio-Res 5 ug/day administration.
      Sixteen symptomatic, never-smoking asthmatics, aged 75 or over with irreversible
      airflow limitation despite the use of high-dose ICS plus LABA, were analyzed.
      RESULTS: All patients were female (mean age, 81.6 years). Tio-Res led to
      statistically significant improvements in the total ACT score (19.9 to 23.6), FVC
      and FEV1 (1.97 to 2.14 L and 1.13 to 1.23 L, respectively), and mPEF and ePEF
      (229.9 to 253.8 L/min and 259.8 to 277.4 L/min, respectively). Tio-Res also
      resulted in statistically significant improvements in respiratory resistance at 5
      Hz (R5), respiratory resistance at 20 Hz (R20), R5-R20, low-frequency reactant
      indices at 5 Hz (X5), resonant frequency (Fres) and low-frequency reactance area
      (ALX). CONCLUSIONS: Our retrospective study suggests that Tio-Res improves
      symptoms, pulmonary function, and respiratory impedance in symptomatic asthmatics
      aged 75 or over with irreversible airflow limitation despite the use of high-dose
      ICS plus LABA.

PMID- 30193396
TI  - Which Antimicrobial Agent is Likely to be the Best for Treating Clostridium
      difficile Infections? A Bayesian Network Meta-Analysis of Randomized Clinical
      Trials.
AB  - BACKGROUND: Vancomycin, metronidazole, fidaxomicin, teicoplanin, fusidic acid and
      bacitracin have been recommended for the treatment of Clostridium difficile
      infections (CDI). We conducted a Bayesian network meta-analysis comparing all the
      antimicrobial agents used in CDI. METHODS: Electronic databases were searched for
      randomized controlled trials comparing antimicrobial agents used for CDI. Risk of
      bias was assessed. Random effects model was used to derive the mixed treatment
      comparison estimates. Odds ratio with 95% confidence intervals was used as effect
      estimate. RESULTS: Seventeen studies were included in this meta-analysis.
      Teicoplanin was observed to perform better than vancomycin, metronidazole,
      fusidic acid and bacitracin to achieve the symptomatic cure. Teicoplanin was also
      associated with higher rates of bacteriological cure than vancomycin and
      metronidazole. Fidaxomicin is associated with significantly higher rates of
      symptomatic cure than vancomycin, bacitracin and metronidazole and is similar to
      teicoplanin. CONCLUSION: To conclude, teicoplanin and fidaxomicin have been
      observed to perform better than other antimicrobials for the treatment of CDI. We
      recommend conducting high quality randomized controlled clinical trials
      evaluating teicoplanin and fidaxomicin with other standard interventions for the
      management of CDI.

PMID- 30193397
TI  - Vanishing refuge? Testing the forest refuge hypothesis in coastal East Africa
      using genome-wide sequence data for seven amphibians.
AB  - High-throughput sequencing data have greatly improved our ability to understand
      the processes that contribute to current biodiversity patterns. The "vanishing
      refuge" diversification model is speculated for the coastal forests of eastern
      Africa, whereby some taxa have persisted and diversified between forest refugia,
      while others have switched to becoming generalists also present in non-forest
      habitats. Complex arrangements of geographical barriers (hydrology and
      topography) and ecological gradients between forest and non-forest habitats may
      have further influenced the region's biodiversity, but elucidation of general
      diversification processes has been limited by lack of suitable data. Here, we
      explicitly test alternative diversification modes in the coastal forests using
      genome-wide single nucleotide polymorphisms, mtDNA, spatial and environmental
      data for three forest (Arthroleptis xenodactyloides, Leptopelis flavomaculatus
      and Afrixalus sylvaticus) and four generalist (Afrixalus fornasini, A. delicatus,
      Leptopelis concolor and Leptopelis argenteus) amphibians. Multiple analyses
      provide insight about divergence times, spatial population structure, dispersal
      barriers, environmental stability and demographic history. We reveal highly
      congruent intra-specific diversity and population structure across taxa, with
      most divergences occurring during the late Pliocene and Pleistocene. Although
      stability models support the existence of some forest refugia, dispersal barriers
      and demographic models point towards idiosyncratic diversification modes across
      taxa. We identify a consistent role for riverine barriers in the diversification
      of generalist taxa, but mechanisms of diversification are more complex for forest
      taxa and potentially include topographical barriers, forest refugia and
      ecological gradients. Our work demonstrates the complexity of diversification
      processes in this region, which vary between forest and generalist taxa, but also
      for ecologically similar species with shared population boundaries.

PMID- 30193398
TI  - Synthesis, Characterization and Photobiological Studies of Ru(II) Dyads Derived
      from alpha-Oligothiophene Derivatives of 1,10-Phenanthroline.
AB  - Three new bis(2,2'-bipyridine)-heteroleptic Ru(II) dyads incorporating thienyl
      groups (n = 1-3, compounds 1, 2 and 3, respectively) appended to 1,10
      phenanthroline were synthesized and characterized to investigate the impact of n
      on the photophysical and photobiological properties within the series. All three
      complexes showed unstructured emission near 618 nm from a triplet metal-to-ligand
      charge transfer (3 MLCT) state with a lifetime (tauem ) of approximately 1 MUs.
      Transient absorption measurements revealed an additional excited state that was
      nonemissive and long-lived (tauTA  = 43 MUs for 2 and 27 MUs for 3), assigned as
      a triplet intraligand (3 IL) state that was accessible only in 2 and 3. All three
      complexes were strong singlet oxygen (1 O2 ) sensitizers, with quantum yields
      (Phi? ) for 2 and 3 being the largest (74-78%), and all three were photocytotoxic
      to cancer cells with visible light activation in the order: 3 > 2 > 1. Cell-free
      DNA photodamage followed the same trend, where potency increased with decreasing
      3 IL energy. Compounds 2 and 3 also showed in vitro photobiological effects with
      red light (625 nm), where their molar absorptivities were <100 m-1  cm-1 . These
      findings highlight that Ru(II) dyads derived from alpha-oligothiophenes directly
      appended to 1,10-phenanthroline-namely 2 and 3-possess low-lying 3 IL states that
      are highly photosensitizing, and they may therefore be of interest for
      photobiological applications such as photodynamic therapy (PDT).

PMID- 30193399
TI  - Performance of multitarget stool DNA testing in African American patients.
AB  - BACKGROUND: Multitarget stool DNA (mt-sDNA) is an approved method for colon
      cancer screening that is especially relevant for patients who cannot undergo
      colonoscopy. Although the test performance has been evaluated in a large clinical
      trial, it was limited to a predominantly white population. Given differences in
      the epidemiology and biology of colon cancer in African American individuals, the
      authors sought to compare the performance of mt-sDNA between racial groups.
      METHODS: The authors prospectively identified patients aged >=40 years who were
      referred for colonoscopy at an academic medical center and 2 satellite
      facilities. Prior to the colonoscopy, the authors collected stool for mt-sDNA and
      fecal immunochemical testing (FIT). They compared the sensitivity, specificity,
      and receiver operating characteristic curve between African American and white
      patients for the detection of advanced lesions or any adenoma. RESULTS: A total
      of 760 patients were included, 34.9% of whom were African American. The
      prevalence of any adenoma (38.9% for African American patients and 33.9% for
      white patients) and that for advanced lesions (6.8% and 6.7%, respectively) were
      similar between groups. The overall sensitivities of mt-sDNA for the detection of
      advanced lesions and any adenoma were 43% and 19%, respectively, and the
      specificities were 91% and 93%, respectively. In general, mt-sDNA was more
      sensitive and less specific than FIT. When stratified by race, the sensitivity,
      specificity, and receiver operating characteristic curve area were similar
      between African American and white patients for both mt-sDNA and FIT.
      CONCLUSIONS: Test performance characteristics of mt-sDNA were comparable in
      African American and white patients. Given the lower uptake of colonoscopy in
      African American individuals, mt-sDNA may offer a promising screening alternative
      in this patient population.

PMID- 30193400
TI  - Seed mucilage interacts with soil microbial community and physiochemical
      processes to affect seedling emergence on desert sand dunes.
AB  - Seedling emergence is a critical stage in the establishment of desert plants.
      Soil microbes participate in plant growth and development, but information is
      lacking with regard to the role of microbes on seedling emergence. We applied the
      biocides (captan and streptomycin) to assess how seed mucilage interacts with
      soil microbial community and physiochemical processes to affect seedling
      emergence of Artemisia sphaerocephala on the desert sand dune. Fungal and
      bacterial community composition and diversity and fungal-bacterial interactions
      were changed by both captan and streptomycin. Mucilage increased soil enzyme
      activities and fungal-bacterial interactions. Highest seedling emergence occurred
      under streptomycin and mucilage treatment. Members of the phyla Firmicutes and
      Glomeromycota were the keystone species that improved A. sphaerocephala seedling
      emergence, by increasing resistance of young seedlings to drought and pathogen.
      Seed mucilage directly improved seedling emergence and indirectly interacted with
      the soil microbial community through strengthening fungal-bacterial interactions
      and providing favourable environment for soil enzymes to affect seedling
      emergence. Our study provides a comprehensive understanding of the regulatory
      mechanisms by which soil microbial community and seed mucilage interactively
      promote successful establishment of populations of desert plants on the barren
      and stressful sand dune.

PMID- 30193401
TI  - Radioiodination and biological distribution of a new s-triazine derivative for
      tumor uptake evaluation.
AB  - A newly synthesized s-triazine derivative 1,1',1"-(((1,3,5-triazine-2,4,6-triyl)
      tris (azanediyl)) tris (benzene-4,1-diyl))tris (ethan-1-one), (1), was
      synthesized as a part of an ongoing research for development of novel s-triazine
      based radiopharmaceuticals. In-vitro cell viability assay against different human
      cancer cell lines showed very promising inhibitory activity of the synthesized
      compound. This finding encouraged the radioiodination of 1 to study the degree of
      its localization in tumor site for evaluating the possibility of its use as a
      tumor imaging agent. The biodistribution study showed good localization of the
      radioiodinated derivative 2 at tumor site following i.v. administration in solid
      tumor-bearing mice. Finally, in a trial to understand the mechanism of the
      anticancer effect exerted by 1, a target prediction study and a docking study
      were performed. The results of the first study showed that focal adhesion kinase
      is a possible target for compound 1 and the docking study confirmed successful
      binding of both compound 1 and its radioiodinated derivative 2 to the binding
      site of focal adhesion kinase. As a conclusion, the results of this study suggest
      that, compound 2 could be used as a potential agent for tumor imaging after
      preclinical trials.

PMID- 30193402
TI  - Molecular evidence for the paraphyly of Scolecophidia and its evolutionary
      implications.
AB  - The phylogenetic relationships between the three main clades of worm snakes
      remain controversial. This question is, however, crucial to elucidate the origin
      of the successful snake radiation, as these burrowing and miniaturized wormlike
      organisms represent the earliest branching clades within the snake tree. The
      present molecular phylogenetic study, intended to minimize the amount of missing
      data, provides fully resolved inter-subfamilial relationships among Typhlopidae.
      It also brings robust evidence that worm snakes (Scolecophidia) are paraphyletic,
      with the scolecophidian family Anomalepididae recovered with strong support as
      sister clade to the 'typical snakes' (Alethinophidia). Ancestral state
      reconstructions applied to three different traits strongly associated to a
      burrowing life-style (scolecoidy, absence of retinal cones and microstomy)
      provide results in favour of a burrowing origin of snakes, and suggest that worm
      snakes might be the only extant fossorial representatives of the primordial snake
      incursion towards an underground environment.

PMID- 30193403
TI  - Viability Criteria for Functional Assessment of Donor Livers During Normothermic
      Machine Perfusion.

PMID- 30193404
TI  - Effect of topical application of 0.5% proparacaine on corneal culture results
      from 33 dogs, 12 cats, and 19 horses with spontaneously arising ulcerative
      keratitis.
AB  - OBJECTIVE: To investigate the effect of topically applied proparacaine on
      bacterial and fungal culture results and to compare cytologic and culture results
      in patients with ulcerative keratitis. PROCEDURE: Corneal samples were collected
      from 33 dogs, 19 horses, and 12 cats with spontaneously arising ulcerative
      keratitis. Samples for bacterial (dogs, cats, horses) and fungal (horses)
      cultures were collected prior to and following application of 0.5% proparacaine
      or saline. All patients then received a topical anesthetic, and samples were
      collected for cytology. Frequency of cultivatable bacteria before (Swab 1) and
      after (Swab 2) application of proparacaine or saline was compared using Fisher's
      exact test. Homogeneity of culture and cytology results was assessed using
      McNemar's test. RESULTS: No difference was detected in number of animals from
      which bacteria were isolated from Swab 1 or Swab 2 for proparacaine (21/37 and
      17/37, respectively) or saline (10/27 and 12/27, respectively). Small numbers
      prevented analysis of fungal culture results in horses between Swab 1 and Swab 2
      for proparacaine (2/12 and 1/12, respectively) or saline (both, 1/8). Bacteria
      were isolated from 10 of 20 horses and detected cytologically in 3 of these;
      fungi were isolated from 3 of 20 horses and detected cytologically in 2 of these.
      Bacteria were detected more frequently using culture (31/64) than cytology
      (19/64). CONCLUSION: Proparacaine did not significantly alter bacterial or fungal
      culture results in cats, dogs, or horses; however, clinical significance warrants
      investigation. Culture and cytology provided complementary data; both should be
      performed to maximize organism detection in patients with ulcerative keratitis.

PMID- 30193405
TI  - Nickel-Based Bicarbonates as Bifunctional Catalysts for Oxygen Evolution and
      Reduction Reaction in Alkaline Media.
AB  - Oxygen electrocatalysis, including the oxygen evolution reaction (OER) and oxygen
      reduction reaction (ORR), is one of the most important electrochemical processes
      for sustainable energy conversion and storage technologies. Herein, nickel-based
      bicarbonates are, for the first time, developed as catalysts for oxygen
      electrocatalysis, and demonstrate superior electrocatalytic performance in
      alkaline media. Iron doping can significantly tune the real valence of nickel
      ions, and consequently tailor the electrocatalytic ability of bicarbonates. Among
      the nickel-based bicarbonates, Ni0.9 Fe0.1 (HCO3 )2 exhibits the highest
      bifunctional catalytic activity, with a potential difference of 0.86 V between
      the OER potential at a current density of 10 mA cm-2 and the ORR potential at a
      current density of -1 mA cm-2 , which outperforms most of the reported precious
      metal-free catalysts. The present work provides new insights into exploring
      efficient catalysts for oxygen electrocatalysis, and it suggests that, in
      addition to the extensively studied transition metal hydroxides and oxides,
      bicarbonates and carbonates also show great potential as precious metal-free
      catalysts.

PMID- 30193406
TI  - Transcriptomic responses to extreme low salinity among locally adapted
      populations of Olympia oyster (Ostrea lurida).
AB  - The Olympia oyster (Ostrea lurida) is a foundation species inhabiting estuaries
      along the North American west coast. In California estuaries, O. lurida is
      adapted to local salinity regimes and populations differ in low salinity
      tolerance. In this study, oysters from three California populations were reared
      for two generations in a laboratory common garden and subsequently exposed to low
      salinity seawater. Comparative transcriptomics was then used to understand
      species-level responses to hyposmotic stress and population-level mechanisms
      underlying divergent salinity tolerances. Gene expression patterns indicate
      Olympia oysters are sensitive to hyposmotic stress: All populations respond to
      low salinity by up-regulating transcripts indicative of protein unfolding, DNA
      damage and cell cycle arrest after sub-lethal exposure. Among O. lurida
      populations, transcriptomic profiles differed constitutively and in response to
      low salinity. Despite two generations in common-garden conditions, transcripts
      encoding apoptosis modulators were constitutively expressed at significantly
      different levels in the most tolerant population. Expression of cell death
      regulators may facilitate cell fate decisions when salinity declines. Following
      low salinity exposure, oysters from the more tolerant population expressed a
      small number of mRNAs at significantly higher levels than less tolerant
      populations. Proteins encoded by these transcripts regulate ciliary activity
      within the mantle cavity and may function to prolong valve closure and reduce
      mortality in low salinity seawater. Collectively, gene expression patterns
      suggest sub-lethal impacts of hyposmotic stress in Olympia oysters are
      considerable and that even oysters with greater low salinity tolerance may be
      vulnerable to future freshwater flooding events.

PMID- 30193408
TI  - Box-Behnken response surface modeling assisted enantiomeric resolution of some
      racemic beta-blockers using HPTLC and beta-cyclodextrin as chiral mobile phase
      additive: Application to check the enantiomeric purity of betaxolol.
AB  - Stereospecific separation method of (+/-) betaxolol, (+/-) carvedilol, and (+/-)
      sotalol using High Performance Thin Layer Chromatography (HPTLC) and beta
      cyclodextrin as chiral selector has been developed and validated. The Box-Behnken
      surface response design was selected for optimizing the operating variables based
      on 15 trials design. The optimized method involves separation on Fluka HPTLC
      silica gel plates 60 F254 (20 * 10 cm) using acetonitrile-methanol-acetic acid
      water (3.4:3.6:0.18:1 v/v) as a mobile phase containing 0.57 mM beta
      cyclodextrin. Densitometric measurements were made at 220 nm for betaxolol and
      sotalol or at 245 nm for carvedilol. Maximum separation of the enantiomers of the
      three drugs was obtained by optimizing concentration of chiral selector, the
      mobile phase composition including acetonitrile amount in the organic part of the
      mobile phase and the volume of acetic acid added. The proposed method enables
      estimation of (-) and (+) enantiomers of betaxolol in drug substance and in
      various pharmaceuticals. The detection limit of betaxolol was 0.15 and 0.13 MUg
      band-1 for (-) and (+) enantiomers, respectively. The detection limits were found
      to be 0.2 and 0.3 MUg band-1 for carvedilol and sotalol, respectively, as
      racemate. In addition, the proposed method was applied in checking the
      enantiomeric purity of (-) BET in the presence of (+) BET at 1% level where the
      inactive (+) enantiomer was quantified with good accuracy and precision at 1%
      level in the active (-) enantiomer.

PMID- 30193407
TI  - An apparatus and method for directly measuring the depth-dependent gain and
      spatial resolution of turbid scintillators.
AB  - PURPOSE: Turbid (powder or columnar-structured) scintillators are widely used in
      indirect flat panel detectors (I-FPDs) for scientific, industrial, and medical
      radiography. Light diffusion and absorption within these scintillators is
      expected to cause depth-dependent variations in their x ray conversion gain and
      spatial blur. These variations degrade the detective quantum efficiency of I-FPDs
      at all spatial frequencies. Despite their importance, there are currently no
      established methods for directly measuring scintillator depth effects. This work
      develops the instrumentation and methods to achieve this capability. METHODS: An
      ultra-high-sensitivity camera was assembled for imaging single x ray interactions
      in two commercial Gd2 O2 S:Tb (GOS) screens (Lanex Regular and Fast Back, Eastman
      Kodak Company). X ray interactions were localized to known depths in the screens
      using a slit beam of parallel synchrotron radiation (32 keV), with beam width
      (~20 MUm) much narrower than the screen thickness. Depth-localized x ray
      interaction images were acquired in 30 MUm depth-intervals, and analyzed to
      measure each scintillator's depth-dependent average gain  RESULTS: Both 
      CONCLUSIONS: The developed instrument and method enable direct measurements of
      the depth-dependent gain and spatial resolution of turbid scintillators. This
      knowledge can be used to predict, understand, and potentially improve I-FPD
      imaging performance.

PMID- 30193409
TI  - Androgen receptor mRNA analysis from whole blood: a low-cost strategy for
      detection of androgen receptor gene splicing defects.
AB  - Androgen insensitivity syndrome (AIS) is caused by defects in the androgen
      receptor (AR) gene and is the most common aetiology of 46,XY disorders of sex
      development. Allelic variants in the AR gene are found in 90% of complete AIS
      (CAIS), but in only 28% to 50% of cases of partial AIS. Even a single nucleic
      acid change can disrupt splicing sites or splicing regulatory sequences,
      resulting in inadequate exon and intron recognition, ultimately leading to an
      aberrant transcript. Therefore, we tested the feasibility of conducting AR cDNA
      analysis from whole blood and from gonadal tissue in a patient with CAIS due to
      AR synonymous mutation (c.1530C > T, p.Ser510Ser; NM_000044.3), which led to an
      aberrant splicing site causing deletion of 92 nucleotides resulting in a very
      short transcript. AR cDNA sequencing was similar in the whole blood and in the
      gonadal tissue, with similar evidence of a consequent altered AR transcript. We
      propose that analysis of AR RNA extracted from whole blood with AR DNA sequencing
      can help to improve the frequency of molecular diagnosis, particularly for
      partial AIS.

PMID- 30193411
TI  - Can a threshold for 11-nor-9-carboxy-Delta9 -tetrahydrocannabinol in hair be
      derived when its respective concentration in blood serum indicates regular use?
AB  - A 100 MUg/L or higher concentration of 11-nor-9-carboxy-Delta9
      tetrahydrocannabinol (THC-COOH) in blood serum is generally assumed to be
      associated with regular and/or heavy use of cannabis. At present, determination
      of the extent of cannabis use by means of the concentration of THC-COOH in hair
      has not been assessed. Therefore, we aimed at establishing a threshold for THC
      COOH concentrations in hair to prove frequent consumption by comparing THC-COOH
      concentrations in 129 corresponding serum and hair samples, respectively. The
      concentration of THC-COOH in the serum was analyzed by gas chromatography-mass
      spectrometry and in the hair by liquid chromatography-tandem mass spectrometry.
      Data were statistically evaluated using receiver operating characteristic curves
      and contingency tables. Our results suggest that a THC-COOH concentration of
      >=4.2 pg/mg in hair was always accompanied by a THC-COOH concentration of at
      least 100 MUg/L in blood serum. Should this be confirmed by further studies of a
      larger study population, a hair concentration of 4.2 pg/mg THC-COOH can be set as
      a threshold to predict regular and/or heavy consumption of cannabis even if no
      corresponding blood sample is available for analysis.

PMID- 30193410
TI  - Cross-European validation of the ItchyQoL in pruritic dermatoses.
AB  - BACKGROUND: Chronic pruritus (CP) is a frequently occurring symptom in
      inflammatory dermatoses, causing a high burden and limitations to health-related
      quality of life (HRQoL). OBJECTIVE: The ItchyQoL was developed to assess the
      impairment to HRQoL in patients with CP. However, it has only been validated in
      English and German. Here, we report the validation in several languages across
      Europe. METHODS: After professional translation, the versions of ItchyQoL were
      digitized for use as a tablet application. Validation was performed in clinics
      for dermatology in Austria, France, Germany, Italy, Poland, Russia, Spain,
      Switzerland and Turkey. RESULTS: Five hundred and thirty-five patients with
      either contact dermatitis, chronic prurigo - nodular type, psoriasis vulgaris,
      lichen planus or mycosis fungoides/Sezary syndrome and with CP >= 3 on the
      numerical rating scale were included. ItchyQoL showed a high level of consistency
      (Cronbach's-alpha, all: 0.95) and test-retest reliability (intraclass
      correlation: 0.91). It strongly correlated with the Dermatology Life Quality
      Index (r = 0.72, P < 0.001) and moderately correlated with itch intensity scales
      in the study population (visual analogue scale r = 0.46; numerical rating scale r
      = 0.51; verbal rating scale r = 0.51, for all: P < 0.001). CONCLUSION: ItchyQoL
      is now also validated in French, Italian, Polish, Russian, Spanish and Turkish
      and can be used in clinical trials in countries speaking these languages.

PMID- 30193412
TI  - [STUDYING THE INTERACTION OF RHESUS MONKEYS WITH THE TACTILE MONITOR DURING THEIR
      OBSERVATION OF LOW-FREQUENCY VISUAL TEST IMAGES].
AB  - In behavioral experiments rhesus macaque monkeys were trained to interact with
      the computer using a tactile display. We used grayscale Gabor patches of low
      spatial frequency as stimuli. Monkeys' task was to touch the screen with his hand
      in the area of the target stimulus, followed by automatic food or juice
      reinforcement. After two successive correct answers, stimulus contrast gradually
      decreased. Using a two-alternative forced choice method the contrast threshold
      was measured within which monkeys can detect the appearance of low-frequency
      images. It was shown that the contrast sensitivity decreased with the decrease of
      stimulus spatial frequency, while the reaction time increased. The findings
      extend our knowledge of the primates' activity in the virtual environment and
      open new possibilities for modeling and studying various human diseases.

PMID- 30193413
TI  - [THE ROLE OF THE BLOOD OXYGEN IN PROTECTIVE MECHANISM OF ISCHEMIC PRECONDITIONING
      DURING HEPATIC ISCHEMIA-REPERFUSION].
AB  - The role of blood oxygen in the protective mechanism of ischemic preconditioning
      (IPC) was investigated in rabbits during hepatic ischemia-reperfusion (HIR).
      Animals were divided into 2 experimental groups: in the 1st group (n = 11)
      hepatic ischemia (30 min) was induced by Pringle maneuver, reperfusion was lasted
      120 min; in the 2nd group (n = 8) the short period of vascular clamping (10 min)
      and reperfusion (10 min) were performed before HIR. The parameters of blood
      oxygen (rO2, p50, Hb), acid-base balance (rN, rSO2, TCO2, ABE, SBE, SBC and
      etc.), lipid peroxidation (Schiff bases, conjugated dienes), antioxidant system
      (catalase, alpha-tocopherol), plasma transaminases (ALT, AST) and nitrite/nitrate
      concentration (NOx) were measured. HIR in the 1st group leads to elevation of
      p50, lipid peroxidation, ALT and AST accompanied by reduction of rN, TCO2, ABE,
      SBE, SBC, catalase activity, alpha-tocopherol and NOx levels. IPC significantly
      reduces p50, lipid peroxidation, ALT and AST simultaneously improves rN, TCO2,
      ABE, SBC, catalase activity, alpha-tocopherol and NOx levels. These findings
      indicate that IPC prevents oxidative stress in liver trough increased blood
      hemoglobin-oxygen affinity and limitation of oxygen participation in free radical
      processes during reperfusion.

PMID- 30193414
TI  - [GROWTH AND RESPONSE OF LEG TISSUES FOR TRANSPHYSEAL OSTEOSYNTHESIS OF TIBIAL
      SHAFT FRACTURE EXPERIMENTALLY].
AB  - Six (6) mongrel dogs at the age of six (6) months underwent transphyseal elastic
      intramedullary osteosynthesis for tibial shaft fracture. Clinical, X-ray, and
      physiological methods were used. As determined, the transphyseal reinforcement of
      the injured bone doesn't influence the lib function, but it retards the segment
      longitudinal growth. The eccentric arrangement of rods leads to forming angular
      deformity of the articular surface. Changes occur in the temperature of the
      covering tissues of the lateral tibial condyle. Consolidation period of the bone
      fragments is not increased. The union is formed through the blood flow of
      hypokinetic type in soft tissues. When intramedullary elastic rods being inserted
      the endosteal and periosteal response contributes to increasing the thickness of
      bone cortical plates and diameter.

PMID- 30193415
TI  - [COMPARATIVE CHARACTERIZATION OF HYALURONIDASE ISOFORMS OF THE 1ST TYPE IN
      SOMATIC TISSUES AND SERUM OF WHITE RATS].
AB  - There are identified 3 proteins with molecular mass of 63, 73 and 132 kDa,
      exhibiting the properties of the hyaluronidase of the 1st type in the liver,
      spleen, renal papilla, skin and serum by the method of zymography. A protein with
      a molecular mass of 73 kDa was detected in all studied tissues and serum, while
      protein with a molecular mass of 63 kDa was present only in the tissues, and the
      protein with molecular mass of 132 kDa was present only in the serum. It is
      discussed the possibility of aggregation of 63 kDa protein molecules in the
      dimers with the formation of a 132 kDa protein in the serum.

PMID- 30193416
TI  - [THE EFFECT OF ERYTHROCYTE MICROVESICLES ON THE AGGREGATION OF PLATELETS].
AB  - We studied the influence of erythrocyte microvesicles, isolated after 4 weeks
      incubation the washed and the unwashed erythrocytes healthy donors from
      preservative, on spontaneous (flow-induced) aggregation of platelets. It was
      found out that microvesicles of the unwashed erythrocytes enhanced the
      spontaneous aggregation of platelets and also formation of fibrin. Microvesicles
      from the washed erythrocytes reduce the platelet aggregation. Possible mechanisms
      of the effect of erythrocyte microvesicles on platelet aggregation were
      investigated.

PMID- 30193417
TI  - [THE EFFECTS AND AFTEREFFECTS OF A SOUND SOURCE APPROACHING AND WITHDRAWING ON
      POSTURAL RESPONSES IN HUMANS ].
AB  - The multimodal influence of the auditory motion adaptation was studied until now
      on visual perception only, however, the auditory motion adaptation can influence
      other modalities. This study is the first attempt to investigate postural
      aftereffects to 45-second adaptation to approaching or withdrawing sound images,
      that were simulated by rhythmic sequences of tone pulses changed linearly in
      amplitude and frequency in the free field. The oscillations of the center of
      pressure in the sagittal plane with the rhythm of stimuli were detected. These
      oscillations were more noticeable for approaching than for withdrawing stimuli
      and resulted in an increase of the length of the trajectory of the center of
      pressure and average linear velocity of its motion. The center of pressure
      shifted in the direction of the sound motion during listening to approaching
      sound images, and to the opposite direction during 20 s after its turning off.
      The shift to the opposite direction demonstrates typical negative aftereffect.
      The data are in accordance with the results of studies of postural responses to
      moving visual stimuli, where the "negative" effect was also revealed.

PMID- 30193419
TI  - [THE SPECIFITY OF MOTOR SYSTEMS ORGANISATION AND IT''S INFLUENCES ON RESULTNESS
      OF ACTIVITY IN HEALTHY PEOPLE AND PATIENTS WITH EPILEPSY].
AB  - The specificity of motor systems and its influences on effectiveness of modeling
      purposeful activity in 46 healthy people and 110 patients with epilepsy was
      studied. Using cluster analysis the patients with epilepsy were divided in 2
      groups: high- and low efficient. The differences of physiological parameters,
      which characterize the activity of central level of motor systems and visual
      motor reaction, were determined. The high level of activation of cortical
      mechanisms of decision-making and preparedness to motor reaction in the group of
      healthy people and low effectiveness associated with insufficient activation of
      these mechanisms in the group of patients with epilepsy was described.

PMID- 30193418
TI  - [THE INFLUENCE OF INFORMATION LOAD ON THE TIMECOURSE OF SPECTRAL PARAMETERS OF
      HEART RATE VARIABILITY IN STUDENTS WITH DIFFERENT CHRONOTYPES].
AB  - In the study, distinctions in daily timecourse of spectral parameters of the
      heart rate variability (HRV) at rest wakefulness and at information load in
      students with different chronotypes are revealed. The most pronounced changes in
      the general spectral power of HRV due to fluctuations of all parameters, but
      especially the VLF, LF, HF waves and the LF/HF index were found in students with
      a daily chronotype at rest and after implementation of load tests during the
      different periods of the school day. In persons with an evening chronotype in
      conditions of rest, the greatest variability was found in a spectral HF component
      of HRV, and responses to information load were found during the day in different
      combinations of changes of LF and HF components and the LF/HF index. In students
      with a morning chronotype during rest wakefulness, considerable fluctuations of a
      proportion of LF waves were observed, whereas in response to information load
      during certain periods of the day, representation of LF and HF components of the
      spectrum was changed. The wide variability of HRV spectral parameters in students
      with daily activity, compared to students with early and late activities,
      reflects the advantages of persons with a daily chronotype in terms of adaptation
      to different operation modes and irregular stress information in the course of
      the day.

PMID- 30193420
TI  - [ROLE OF ENDOGENOUS OPIOID SYSTEM IN THE REGULATION OF FUNCTIONAL STATE OF
      HEART].
AB  - The cardiovascular effects of opioid peptides may be associated with activation
      of opioid receptors located on the sarcolemma of cardiomyocytes, on the cell
      membrane of ICA and endothelial cells, on sympathetic and parasympathetic nerve
      terminals in the heart and in the adrenals. The cardiovascular effects of opioids
      penetrating the blood-brain barrier may be the result of their impact on central
      opioid receptors.

PMID- 30193421
TI  - [ADENYLYL CYCLASE SIGNALING SYSTEM IN THE LIVER AND PANCREAS INNORM AND IN
      DIABETIC PATHOLOGY].
AB  - The adenylyl cyclase signaling system (ACSS) mediates the regulatory effects of
      many hormones on cell and controls a wide spectrum of physiological functions. In
      the liver ACSS is involved in the regulation of metabolic processes, and controls
      cell survival. In the endocrine pancreas the regulation of the main function of
      beta-cells, such as glucose-stimulated insulin secretion is carried out via this
      system. Soluble forms of adenylyl cyclase, along with the membrane-bound forms of
      the enzyme, play an important role in the control of cAMP level in beta-cells. In
      diabetes mellitus (DM), the disturbances in the different components of ACSS in
      hepatocytes and beta-cells are observed. Their identification is essential for
      the diagnosis, treatment and prevention of diabetic diseases, especially type 2
      DM, in which the ACSS-mediated regulation of carbohydrate and lipid metabolism in
      the liver, and cAMP-dependent insulin secretion in the beta-cells are impaired.
      In the review the structural-functional organization and regulatory properties of
      ACSS in the liver and endocrine pancreas, and also the disturbances occurring in
      this system in DM are analyzed.

PMID- 30193422
TI  - [THE STRUCTURAL ASPECTS OF THE PARTICIPATION OF THE BRAINSTEM NUCLEI IN THE
      PROCESSING OF THE FUNCTIONALY DIFFERENT INFORMATIONAL FLOWS GOING THROUGH THE
      BASAL GANGLIA].
AB  - The structural foundation of processing of the information in the basal ganglia
      morphofunctional system was examined on the basis of the analysis of the
      investigated by the method of retrograde axonal transport projections between the
      functionally different parts of brain steam and basal ganglia' functionally
      various segments. The elements of the topic, showing to opportunity of segregated
      carrying of the information between the limbic and motor segments of the brain
      steam and the basal ganglia' similar regions were revealed in the organization of
      the projections between the named structures in dog. But, in the considered
      projection systems prevail the convergent carrying of the information testified
      about the possibility of the integration different modal information not only in
      the basic, but and in the all nuclei of the basal ganglia' morpho-functional
      system. The labeled "reticular" neurons with sparsely branching dendrites and
      long axons, which are projected to the basal ganglia, also testify about the
      integrative function of the investigated nucleus. The opportunity of the
      utilization of the received dates for making of the new models, which allow to
      understand better the mechanism of basal ganglia functioning in norm and
      pathology are discussed.

PMID- 30193423
TI  - [THE INFLUENCE OF OPIOID PEPTIDES DSLET AND DAGO ON LIPID PEROXIDATION AND THE
      ACTIVITY OF ANTIOXIDANT ENZYMES IN THE LIVER TISSUE OF RATS IN THE STRESS OF
      DIFFERENT DURATION].
AB  - It was established that immobilization stress of different duration (3, 6 or 12
      hours) causes the activation of lipid peroxidation in liver tissue of rats 39
      hours after stressor action. Activation of lipid peroxidation within 7 days was
      observed in animals exposed to 6 or 12 hours stress. The activation of superoxide
      dismutase and catalase activity was revealed in rats after 3 hours immobility,
      but 12 hours stress was accompanied by superoxide dismutase inhibition. Agonists
      of different opioid receptors were shown to afford the antioxidant effects
      inhibiting the accumulation of malondialdehyde and acylhydroperoxides in the
      liver tissue and stimulating the antioxidant enzyme activity. Opioid peptides had
      a stimulatory effect on superoxide dismutase activity and less one on catalase
      activity in animal exposed to immobilization of different duration. A selective
      agonist of opioid delta-receptors DSLET manifested more expressed antioxidant
      effect, causing the inhibition of LPO metabolites production and the stimulation
      of superoxide dismutase and catalase activity.

PMID- 30193424
TI  - [THE DYNAMICS OF ENERGY SUBSTRATE CHANGES IN MICE MUSCLES AND LIVER AFTER
      SKELETAL INJURY THROUGH LIMB GRAVITATION UNLOADING].
AB  - The authors studied the content of creatine phosphate, creatine and glycogen in
      skeletal muscles and that of glycogen in the liver of mice from three
      experimental groups. The animals of Group 1 (n = 18) underwent leg bone fracture
      modeling; those of Group 2 (n = 18) - modeling of limb gravitation unloading by
      their weight-bearing deprivation; the animals of Group 3 (n = 18) after modeling
      a leg bone fracture underwent weight-bearing deprivation in the model of
      gravitation unloading. As for Comparison Group, the same parameters studied in
      the intact animals at the age of two (n = 14) and three (n = 12) months. The
      authors found the decrease in the total content [creatine phosphate+creatine] and
      glycogen level in skeletal muscles of Group 1 and 2 mice in the process of the
      experiment, that was not observed in Group 3 mice. They concluded that the
      special features of the changes in the studied substrates of Group 3 mice were
      the consequence of the compensation of the increased energy due to injury by
      hypofunction of the muscle as a result of its gravitation unloading.

PMID- 30193425
TI  - [SEASONAL FEATURES OF SEROTONIN IN BLOOD SERUM OF RATS AFTER PHYSICAL OVERWORK
      UNDER DESYNCHRONOSIS].
AB  - The content of serotonin in the blood serum of rats with light desynchronizes and
      physical fatigue in different seasons was investigated vu enzyme immunoassay. It
      was found that long-term light deprivation and exercise to complete depletion
      lowered levels of serotonin in the blood serum of rats in the winter and
      increased that of the spring season. At the same time, a dark deprivation and
      physical activity had no effect on this indicator.

PMID- 30193426
TI  - [EFFECTS OF IN VITRO CULTURE AND EMBRYO TRANSFER ON THE ARTERIAL BLOOD PRESSURE,
      BODY WEIGHT AND BEHAVIOUR IN ISIAH RATS].
AB  - This study was the first to investigate long-term effects of in vitro culturing
      of embryos combined with their cryopreservation and transfer on arterial blood
      pressure, body weight and behavior in hypertensive rats. No differences in body
      weight and arterial blood pressure levels were found between the naturally born
      rats and those born with the help of ART (assisted reproductive technologies).
      However, ART-born rats spent more time on rearing, as was revealed by the open
      field test. The results of the elevated plus maze test indicated that these rats
      spent more time in the open arms and demonstrated a longer duration of head dips.
      Moreover, the light-dark box test showed a longer total leaning-out time in this
      group. Taken together, the results of the three behavioral tests demonstrate a
      greater exploratory activity and lower anxiety in ART-born ISIAH rats than in
      natural born ones.

PMID- 30193427
TI  - [SECOND MESSENGERS IN PRESYNAPTIC REGULATION OF GLYCINERGIC SYNAPSE ON THE FROG
      MOTONEURON].
AB  - The possible pathways of inhibitory influences mediated by two kinds of
      metabotropic receptors, group III metabotropic glutamate receptors (mGluRs III)
      and GABAB receptors (GABABRs) to the miniature glycinergic events were
      investigated in the isolated spinal cord of the frog Rana ridibunda. The
      glycinergic events prevailed within the miniature inhibitory activity of
      motoneurons [3]. Selective agonists of GABABRs (baclofen) and group III mGluR
      (LAP4) reduce the frequency of miniature events to 48.0 +/- 5.56% (n = 8) and
      48.5 +/- 8.6% (n = 5) respectively. The mean amplitude of miniature potentials
      was not modified significantly which indicates the presynaptic mode of their
      action on the synaptic transmission. To reveal the stages of metabotropic
      receptors regulatory effects on the glycine exocitosis the application of their
      selective agonists was performed after selective blockade of putative links of
      glycinergic transmission modulation. It was shown that the mGluRsIII influences
      are due to the negative feedback with adenylyl cyclase (AC) whereas the following
      step is formed by protein kinase A (PKA), because their selective blockade
      eliminate the effect of group III mGluRs activation. The AC is not involved in
      transdusing the GABABRs signal to the glycine miniature activity because SQ22536,
      an AC-inhibitor does not eliminate the inhibitory action of baclofen. The action
      of GABABRs depends on the activity of the phospholipase C (PLC) because its
      inhibition with U73122 prevents the effect of baclofen. The next possible link of
      this pathway could be the protein kinase C (PKC); but it is not involved in the
      realization of GABABRs influences because the PKC blocker (GF 109302X) does not
      modify the baclofen effect. The common link of group III mGluRs and GABABRs
      influences on the glycinergic miniature activity realization can be the inositol
      trisphosphate receptors (IP3Rs) that regulate the Ca2+ outflow from the nerve
      terminal depots and are connected (according to the literature data) with PKA,
      cAMP and PLC. In our experiments 2-APB, an IP3Rs antagonist, reduced to 26 +/- 8%
      (n = 7) the frequency of glycinergic miniature activity and prevented the
      inhibitory effects of group III mGluRs and GABABRs. Our data suggest that
      collision and cross-talk of these Glu- and GABA-metabotropic pathways which was
      described earlier [2] may take place at this level.

PMID- 30193428
TI  - [EFFECT OF THE PROLYL-GLYCIL-PROLINE (PGP) AND ITS ACETYLATED FORM (N-AcPGP) ON
      PERMEABILITY OF SKIN VESSELS IN RATS].
AB  - This study is dedicated to the research of the regulatory peptide PGP and its
      acetylated form (N-AcPGP) effect on the paw edema formation and vascular
      permeability in rat skin. Edema was induced by subcutaneous administration of
      histamine. Vascular permeability was determined by intradermal injection of mast
      cells activators corticotropin-releasing hormone (CRH), lipopoly-saccharide
      (LPS), Synacthen (corticotropin analogue), histamine and compound 48/80. We
      established that PGP reduced the size of the paw edema, but N-AcPGP had an
      opposite effect increasing paw edema. Skin vascular permeability didn't increase
      in rats under the administration of PGP or N-AcPGP with additional injections of
      CRH, LPS and Synacthen, but with additional injections of histamine and substance
      48/80. We demonstrated in vitro that pretreatment with both PGP and N-AcPGP
      reduced histamine secretion by rat's peritoneal mast cells under activation by
      Synacthen. These results provide evidence that the effect of the peptides on
      vascular permeability is mainly mediated by the influence on the secretory
      activity of mast cells.

PMID- 30193429
TI  - [DIRECT EFFECT OF IL-7 ON THE GROWTH AND FUNCTIONAL ACTIVITY OF T-LYMPHOCYTES IN
      THE ABSENCE OF ANTIGENIC STIMULUS].
AB  - It is shown that in the absence of antigenic stimulus interleukin-7 (IL-7) is
      capable of increasing the content of cells expressing the CD25 molecule among
      both CD4-positive and CD4-negative effector memory T-cells (CD45RA-CD197-), as
      well as terminally differentiated T cells (CD45RA+CD197-) without causing a
      significant impact on the status of the activation of naive T cells
      (CD45RA+CD197+) and central memory T cells (CD45RA-CD197+). IL-7 was also able to
      enhance T-cell production of IL-2, interferon-gamma (IFN-gamma) and IL-10, but
      not IL-4. These data indicate the involvement of IL-7 into a direct upregulation
      of growth and functional activity of human T cells in the absence of antigenic
      stimulus and the relative scarcity of costimulatory effects.

PMID- 30193430
TI  - [INFLUENCE OF FUNCTIONAL MUSCULAR TEST ON BLOOD FLOW VELOCITY ON MEDIAL CEREBRAL
      ARTERY DURING TREATMENT OF PATIENTS BY G. A. ILIZAROV].
AB  - It was evaluated the influence of functional test on blood flow velocity (BFV) on
      medial cerebral arteries (MCA) at healthy persons of different age (30 persons at
      the age of 5-60 y. o.) and in patients (28) during operative limb lengthening for
      2-15 cm. BFV was examined by the ultrasonic dopplerography method at rest, and
      repeated on both brain sides in handhold of gripper by right hand then left one.
      In healthy persons, with age increasing, reduction of BFV on MCA was observed,
      and was more significant in patients with orthopaedic pathology. In four-time
      repetition of functional test variants, maximum range of BFV variation on MCA did
      not grow out of 17-25 %. During the process of operative limb lengthening in
      significant reduction of BFV on MCA and increasing of range BFV variation,
      working capacity of patients was disturbed. Age-delayed BFV on MCA develop slowly
      with a saving of BFV changes variability, it is a prerequisite of saving of brain
      centers function.

PMID- 30193431
TI  - [DOPAMINE STIMULATION AFFECTS MULTIPLE - FOOD - UNIT PREFERENCE IN RATS].
AB  - It has been shown that food seeking behavior in rats performing in different
      types of mazes is controlled by discrete reward pattern related to change in
      attractive properties of reinforcement and dopamine activity plays a critical
      role in motivation and food preference processing. The data obtained suggest that
      behavior as well as amphetamine effects revealed under the exposition of the
      discrete reward paradigm of learning may be involved in a common mechanism
      underlying food disorders and drug addiction in humans.

PMID- 30193432
TI  - [THE DAMAGING EFFECTS AT AN EARLY AGE ALTER PAIN SENSITIVITY IN ADULT FEMALE
      RATS, CORRECTION WITH BUSPIRONE].
AB  - Most studies on the damaging effects of pain and stress impacts in the neonatal
      period of development on pain sensitivity were performed on individuals of the
      male sex. In the present study, we investigated the influence of inflammatory
      pain and/or stress of isolation from the mother in newborn female rats to pain
      sensitivity when they reached adulthood; an attempt was undertaken to correct
      identified deviations using 5-HT1A-receptor agonist buspirone. Adult females
      exposed to early pain displayed increased hypoalgesia in the hot plate test and
      rats subjected to stress of isolation from the mother showed increased
      hyperalgesia in the formalin test. The pain and subsequent isolation from the
      mother did not change pain sensitivity in the adult females. The chronic
      injection of buspirone from 25 th to 39 th day of life to females subjected to
      inflammatory pain and isolation from the mother in the neonatal period caused the
      normalization of pain sensitivity when they reached adulthood. It is found that
      the prepubertal period is a critical period for the correction of deviations
      caused by damaging impacts in neonatal rata in the functional activity of the
      nociceptive system.

PMID- 30193433
TI  - [CAT'S VISUAL AREA 18 INTERMODULAR INTERACTIONS DEVELOPMENT UNDER DIFFERENT
      VISUAL ENVIRONMENT].
AB  - Primary visual cortex contains a set of modules, and their postnatal development
      depends on a combination of internal genetic and external (defined by visual
      environment) factors. In order to examine a development of intermodular
      interactions in visual cortex of kittens subjected to rhythmic light stimulation
      (15 Hz and 50 Hz frequencies, groups RLS-15 and RLS-50), we investigate an
      intermodular signal correlation by mean of optical imaging technique. Data was
      compared with control kittens and with kittens reared with no visual experience
      in total darkness (group DARK). A significant reduction of the intermodular
      correlation coefficient was obtained in the group RLS-15; the correlation
      coefficient values in the groups RLS-50 and DARK was not affected. Thus 15 Hz
      rhythmic light stimulation during sensitive periods of development disrupts an
      efficacy of intermodular neuronal connections.

PMID- 30193434
TI  - [INVOLVEMENT OF THE NITRERGIC SYSTEM OF THE PREFRONTAL CORTEX IN FEAR EXPRESSION
      INDUCED BY CONTEXTUAL SIGNALS OF DANGER].
AB  - In Sprague-Dawley rats by means of in vivo microdialysis, we have shown that
      presentation to rats a conditioned chamber in which a ton was previously paired
      with footshock (acquisition of a conditioned fear response to the tone) produces
      an increase in extracellular levels of citrulline (an NO co-product) in the
      medial prefrontal cortex and results in freezing response (fear index). This
      increase was not observed in control rats (same procedure, no footshock) and it
      was prevented by infusions into the medial prefrontal cortex of N(r)-propyl-L
      arginine (1 mM), a neuronal NO synthase inhibitor. The infusion of 1mM N(r)
      propyl-L-arginine into the medial prefrontal cortex reduced freezing to the
      conditioned chamber, but did not affect movement activity of the rats. Data
      obtained indicate that the nitrergic system of the medial prefrontal cortex
      implicates in regulation of fear expression produced by contextual signals of
      danger.

PMID- 30193435
TI  - [PARTICIPATION OF GASEOUS TRANSMITTERS IN BLOOD OXYGEN TRANSPORT FUNCTION
      MODIFICATION UNDER THE INFLUENCE OF MAGNETIC FIELD].
AB  - Gaseous transmitters contribution in blood oxygen transport function modification
      under the influence of the magnetic field was studied. It is found, that
      irradiation of the tail artery of rats for 10 days during 10 minutes increases
      p50 value, indicating a decrease in the hemoglobin affinity for oxygen and is
      accompanied by increased concentrations of nitrate/nitrite, and hydrogen sulfide.
      Administration of L-arginine and nitroglycerin during magnetic field action is
      accompanied by a decrease of hemoglobin affinity for oxygen, which is absent when
      NO-synthase enzyme inhibitor (L-NAME) is added. These data suggest an important
      role in the formation of blood oxygen transport function such gaseous
      transmitters as nitrogen monoxide and hydrogen sulfide.

PMID- 30193436
TI  - [EFFECTS OF ORALLY AND PARENTERALLY ADMINISTERED ANALOGS OF PEPTIDE HORMONES ON
      RENAL WATER AND ION TRANSPORT].
AB  - In experiments with female Wistar rats it was shown that analogs of
      neurohypophysial hormones administered to gastrointestinal tract preserved their
      specific physiological activity - they increased solute-free water reabsorption
      and urinary sodium and potassium excretion. Doses of deamino-vasotocin exerted
      antidiuretic and natriuretic effects following its oral administration were 50
      and 200 times higher compared to maximal effective ones after intramuscular
      injection. Inhibition of gastrointestinal proteases by aprotinine enhanced
      effects of nonapeptides; the amount of peptide absorbed from the intestine under
      these conditions was approximately 0.5 % of orally introduced substance. In
      contrast to analogs of neurohypophysial nonapeptides, glucagon-like peptide-1
      mimetic (exenatide) did not exert its physiological effects after oral
      administration, whereas it increased urinary sodium and potassium excretion
      following intramuscular injection.

PMID- 30193437
TI  - [INVOLVEMENT OF 5-OPIOID RECEPTORS IN THE INCREASED RESISTANCE OF HEART AND
      MITOCHONDRIA TO IMPACT OF ISCHEMIA-REPERFUSION AFTER ADAPTATION TO CHRONIC
      CONTINUOUS HYPOXIA].
AB  - It was investigated the involvement of cardiac ?-opioid receptors (OR) in
      increasing the resistance of the heart and myocardial mitochondria to ischemia
      reperfusion after adaptation rats to chronic continuous normobaric hypoxia
      (CCNH). Rats were subjected to CCNH for 21 days at 12 % O2. It was evoked global
      ischemia (45 minutes) and reperfusion (30 minutes) of the isolated perfused
      heart. Adaptation to CCNH promoted a reduction of creatine kinase release from
      necrotic cardiomyocytes during reperfusion and improved reperfusion recovery of
      heart contractility. Mitochondrial respiratory and state of MPT pore were more
      resistant to ischemia-reperfusion in adapting rats. Perfusion of isolated hearts
      with TIPP(0) (30 nM/l, a selective ?-OR-antagonist) or naltriben (1 nM/l, a
      selective 52-OR-antagonist) completely eliminated the cardioprotective effect of
      CCNH. BNTX (1 nM/l, a selective ?-OR-antagonist) had no effect on the
      cardioprotective effect of CCNH. This data suggest that cardiac 52-OR involved in
      the increased resistance of the heart and mitochondria to ischemia-reperfusion
      after adaptation rats to CCNH.

PMID- 30193438
TI  - [INTERACTION EPITHELIUM AND SMOOTH MUSCLE IN THE WALLS OF THE AIRWAYS IN THE
      NORMAL CONDITIONS AND WHEN FORMING OF HYPERREACTIVITY].
AB  - In the present study was to investigate the effect epithelium on the tone smooth
      muscle of the airways of guinea pigs under physiological conditions and when
      forming of experimental asthma. It was found that the amplitude of contractile
      responses decreased by histaminergic, and serotonergic effects in the presence of
      epithelium in the control group. Influence epithelium dilatation adrenergic
      reactions depended on the type of pretreatment factors. The amplitude of the
      relaxation was reduced in the case of pre-treatment with a solution of potassium,
      the amount of dilation increased by pretreatment with histamine. The impact of
      epithelium on contractile responses of smooth muscles disappeared when forming of
      hyperreactivity.

PMID- 30193439
TI  - [ERYTHROKARIOCYTES APOPTO- TIC ACTIVITY IN ERYTHROBLASTIC ISLANDS OF RATS BONE
      MARROW].
AB  - The functional activity of bcl-2 andp53 proteins in erythrokariocytes of
      erythroblastic islands (EI) of various classes of bone marrow belonging to intact
      rats and animals following an acute blood loss were investigated. It is observed
      that intact rats had the elevated levels of percent content of bcl-2+
      erythrokariocytes in EI of the second maturity class, compared to EI of first
      maturity class and EI involutionary class, and also less in the EI involutionary
      class compared to EI 1 and EI 2. The percentage content of p53+ erythrokariocytes
      in intact rats in the EI 2 class was less than in EI 1 and EI involutionary
      class, and were nearly the same of EI 1, EI 3, EI involutionary class and EI
      reconstructed. 48 hours after blood loss, the content of bcl-2+ erythrokariocytes
      were increased in EI 1, EI 2, and EI reconstructed.

PMID- 30193440
TI  - [PHYSIOLOGICAL TREMOR INSTANTANEOUS FREQUENCY DYNAMICS UNDER VARIOUS EMOTIONALY
      LOADED STIMULATION].
AB  - Emotionally evoked physiological tremor dynamics was investigated on varying
      stimulus efficiency. Experimental protocol includes randomized presentation of
      four variant visual stimuli, one of the followed - subject's second name, random
      shuffled letters of second name, graphic representation of simple arithmetic
      expression with correct or incorrect answer. The physiological tremor acquisition
      was implemented by 3-axial digital accelerometers, fixed on external side of
      index fingers. The data analysis explained unconscious psychomotor activity
      dynamics under emotional status transitions. Evoked reactions specificity gives
      an opportunity to suppose stimulus-dependent lateralization of unconscious motor
      responses. Valid differences of the right hand psychomotor reactions were
      achieved for the most emotionally loaded stimulus - second name.

PMID- 30193441
TI  - [SACCADES AND PRESACCADIC SPIKE POTENTIAL DURING THE GAME OF TETRIS].
AB  - Saccades and microsaccades were studied during a game of Tetris using the method
      of EOG. In the experiments 19 players of different skill level were involved. EOG
      was recorded in monopolar mode with respect to the ear electrodes in 6-points
      around both eyes to account for the gaze displacement in 8-direction. The game of
      Tetris was on 3 difficulty levels. It is shown that each saccade on EOG preceded
      by a sharp negative potential of 10-15 ms or "pre-saccadic peak". Its parameters
      are very stable at the given person, while EOG parameters of themselves saccade
      vary from their direction. When bipolar registration peak is not detected. The
      peak amplitude does not depend on the saccade direction, but correlates with
      saccade amplitude. It is assumed that the peak generators are neuromuscular
      synapses. Everything else being equal men were characterized by shorter saccades
      and greater percentage of microsaccades than women. On the middle level of
      difficulty at the optimal level of attention (but without the stress) are
      observed smallest saccades. For all players have dominated vertical saccades from
      the block to the glassful bottom and backward. In the transition from light to
      hard level for experienced players is increasing the proportion of "extra" non
      vertical saccades, while the proportion of beginners "extra" saccades always
      relatively high.

PMID- 30193442
TI  - [OLFACTORY EEG PATTERNS OF MENTAL AND BEHAVIORAL DISORDERS DUE TO PSYCHOACTIVE
      SUBSTANCE USE].
AB  - The 74 persons, including the 39 persons with mental and behavioral disorders due
      to psychoactive substance use (PAS) and the 35 persons with subclinical forms of
      substance use, are examined. The olfactory EEG patterns, differing in
      narcological patients depending on the range of PAS used, are revealed. EEG
      markers of olfactory response to isopropanol, thymol and androstenone in
      combination with emotional evaluation, having hemispheric features, can be
      diagnostic and differential predictive factors for assessment of predisposition
      to mental and behavioral disorders due to PAS use.

PMID- 30193443
TI  - [STUDY OF INFLUENCE OF SIMULATED WEIGHTLESSNESS AND LUNAR GRAVITY TO
      BIOMECHANICAL PARAMETERS OF HUMAN WALKING].
AB  - The paper presents the results of a comparative analysis of the biomechanical
      characteristics human's walking before and after a stay in a long-term head-down
      bed rest at a -6 degrees angle simulating a microgravity (the HDBR-group) and in
      head-up bed rest (HUBR) at a +9.6 degrees angle as a analogue of lunar gravity
      (the HUBR-group). The biomechanical characteristics of the walking on a treadmill
      pace of 60 steps/minute before and after bed rest were analyzed. We investigated
      also the electromyographic characteristics of leg muscles and recorded the angles
      in the following joints: hip joint, knee joint and ankle joint. The most
      pronounced effect on the parameters of the humans walking was found in the HDBR
      group. It was manifested in the changes of angles in the leg joints at various
      phases of a step change and in an electromyographic activity of muscles. Similar,
      but less pronounced changes of walking biomechanical characteristics were found
      after bed rest in the HUBR-group.

PMID- 30193444
TI  - [THE ROLE OF THE ENDOGENOUS CANNABINOID SYSTEM IN THE FORMATION OF THE GENERAL
      ADAPTATION SYNDROME].
AB  - Nonopioid stress-induced analgesia is the consequence of activation of CB1
      receptors by the increased level of 2-arachidonoyl glycerol, anandamide in the
      periaqueductal gray matter in the midbrain. The activation of cannabinoid CB1
      receptors inhibits stress-induced ulcerogenesis due to the strengthening of the
      antioxidant defense of the gastric mucosa. CB1 receptor antagonists promote an
      increase in ACTH and corticosterone concentrations in the blood of intact
      animals, the knockout of the gene encoding the CB1 receptor exhibits the same
      effect. Antagonists of CB1 receptors enhance the stressor elevation of ACTH and
      corticosterone levels in the blood of experimental animals. It was found an
      increase in stress-induced elevation of corticosterone and ACTH levels in the
      blood of mice with a knockout of the gene encoding the CB1 receptor. An increase
      in the endogenous anandamide level or disturbance of the reuptake of endogenous
      cannabi-noids after application of pharmacological agents promotes reducing
      corticosterone level in stressed animals. Consequently, endogenous cannabinoids
      inhibit basal and suppress stress-induced activity of the hypothalamic-pituitary
      adrenal axis. The indicated regulation is carried out on the level of the
      hypothalamus, pituitary and adrenal cortex. Stimulation of central cannabinoid
      receptors leads to an activation of the sympathetic system. The activation of
      peripheral CB1 receptors leads to inhibition of norepinephrine release from
      sympathetic terminals and epinephrine release from the adrenal glands. The
      endogenous CB1 receptor agonists play an anxiolytic role and prevent the
      occurrence of pathological anxiety.

PMID- 30193445
TI  - [THE ROLE OF LYMPHOCYTIC RNA IN THE INTERCELLULAR INFORMATION EXCHANGE AND IN THE
      REGULATION OF REGENERATIVE PROCESSES].
AB  - The review presents facts telling about the involvement of RNA of lymphocytes
      into regulation of proliferation and differentiation of cells in various tissues.
      There are considered: transport mechanisms of exogenous RNAs in cells, the role
      of non-coding RNAs molecules in the regulation of embryonic and postnatal
      morphogenesis. The long non-coding RNAs and microRNAs of T-lymphocytes are
      characterized, also there is made a comparative analysis of different microR-NAs
      expression in T cells and the regulatory effects of these molecules in reparative
      processes. There are described the RNA technologies, stimulating the anti-tumor
      immunity and regeneration of damaged tissues used in clinical practice, and also
      the perspectives of creating new treatments based on the use of RNA preparations.

PMID- 30193446
TI  - [EFFECTS OF URGENT RELEARNING ON THE PERFORMANCE OF THE SPATIAL TASKS].
AB  - Introducing of urgent relearning in radial maze, consisting of one or two shifts
      of reward position in raw without any gap between behavioral sessions, resulted
      to inability of animals to use optimal navigational strategy to find preferable
      reward in maze while keeping responding to int-ra-maze stimuli. Procedural
      introducing of time-out between tested behavioral sessions, which was accompanied
      by sleep generated naturally or induced by injection of neuropeptide ACTH 18-39,
      resulted to considerable improvement of relearning in radial maze as well as
      reducing per-severative behavior and attempts to refuse from responding. The data
      obtained demonstrate the important role of sleep for successful urgent relearning
      in radial maze and preventing possible neurological disorders.

PMID- 30193447
TI  - [ANTIANHEDONIC EFFECT OF 3-OXYPYRIDINE AND SUCCINIC ACID DERIVATIVES].
AB  - We performed a comparative study of the effect of original domestic derivatives
      of 3-oxypyri-dine and succinic acid (emoxipine, reamberin and mexidol) on
      measures from "sucrose preferen-ce" test which is used for assessment of hedonic
      behavior in rats. a-lipoic acid (a-LA) and amit-riptylin were used as reference
      medications. For the modeling of anhedonia rats received dexa-methasone (5 mg/kg
      subcutaneously). We established that threefold administration of emoxipine,
      reamberin and mexidol in doses that are equivalent to therapeutic range in humans
      had antianhe-donic effect and increased the measures of "preference" and absolute
      sucrose consumption. This effect was demonstrated in animals that did not receive
      dexamethasone as well as in rats with dexamethasone-induced anhedonia. Maximal
      intensity of antianhedonic effect of 3-oxypyridine and succinic acid derivatives
      was noted after the previous administration of dexamethasone. In rats that did
      not receive dexamethasone, succinate-containing medications (reamberin and
      mexidol) exceeded the isolated 3-oxypyridine derivative (emoxipine) in their
      antianhedonic potential. In case of previous dexamethasone administration 3
      oxypyridine and succinic acid derivatives demonstrated equivalent antianhedonic
      effect that exceeded the effect of reference medications (a-LA and amitriptylin).

PMID- 30193448
TI  - [INFLUENCE OF PROBIOTIC STRAIN E. FAECIUM L3 ON MYOCARDIAL TOLERANCE TO ISCHEMIA
      REPERFUSION INJURY IN THE MODEL OF ANTIBIOTIC-INDUCED INTESTINAL DYSBIOSIS].
AB  - Functional parameters and degree of myocardial damage by ischemia-reperfusion
      model of isolated heart were investigated during acute experiments on rats with
      an antibiotic-induced intestinal dysbiosis after administration of the probiotic
      strains of Enterococcus faecium L3. Administration of antimicrobial drugs has
      resulted in an increased heart rate and in an increase in coronary flow of
      isolated heart. Administration of enterococci after the global ischemia has
      caused rats to have a decrease in diastolic pressure, increased systolic and
      pulse pressure, and an increased intensity of coronary flow. The article presents
      data on changes in the composition of the intestinal microbiota and the immune
      system that was previously obtained in studies based on this experimental model.

PMID- 30193449
TI  - [EFFECTS OF PROINFLAMMATORY CYTOKINE INTERLEUKIN-1P ON RESISTANCE TO ACUTE
      HYPOXIA].
AB  - Under a progressive growth of acute hypoxia the effect of high systemic levels of
      proinflammatory cytokine interleukin-1 R (IL-1R) were studied the reactions of
      the cardiorespiratory system of anesthetized Wistar rats. The results suggest a
      negative effect of IL-1 R on the control mechanisms the respiratory and
      cardiovascular system, which was reflected in the reduction of resistance to
      acute hypoxia and the ability to spontaneous autoresuscitation after apnea in
      posthypoxic period, as well as in the development of circulatory collapse. It is
      assumed that the basis of the resistance mechanisms of the body to reduce the
      hypoxic exposure is multifactorial effects of increased levels of IL-1 R,
      activation of HIF-1 a and NO production in the operation of the systems
      responsible for maintaining oxygen homeostasis.

PMID- 30193450
TI  - [INFLUENCE OF R-ENDORPHIN ON FUNCTIONAL ACTIVITY OF ISOLATED RAT HEART].
AB  - We have studied the effect of R-endorphin (an endogenous opioid peptide) on the
      functional characteristics of isolated rat heart. In physiological concentrations
      (6.3 X 10-10 M) R-endorphin induces a negative inotropic effect, accompanied by a
      slight decrease in the heart rate, and has no effect on the perfusion pressure of
      the coronary vessels. It is shown that the effect of R-endorphin is mediated by 5
      opioid receptors. ATP-dependent K+-channels contribute the greatest contribution
      to the implementation of the effect of R-endorphin on the isolated heart of a
      rat. The role of voltage-dependent K+-channels and NO-mediated mechanisms in the
      implementation of the effects of R-endorphin is minor.

PMID- 30193451
TI  - [GASTROPROTECTIVE EFFECT OF CORTICOTROPIN-RELEASING FACTOR IN STREPTOZOTOCIN
      INDUCED DIABETIC RATS].
AB  - The results of our previous studies suggest that corticotropin-releasing factor
      (CRF) protects the gastric mucosa of rats against stress- and indomethacin
      induced gastric injury. In the present study, we investigated whether CRF may
      protect gastric mucosa against indomethacin-induced gastric injury on diabetic
      rats. Diabetes was induced by streptozotocin (70 mg/kg) 14 days before
      indomethacin injection. CRF (2.5 |xg/kg) and CRF receptor antagonists were
      injected 15 min before indomethacin. The diabetes development resulted in the
      aggravation of gastric mucosal erosion produced by indomethacin. Intraperitoneal
      CRF administration caused pronounced gastropro-tective action in control as well
      as diabetic rats that resulted in significant attenuation of indomethacin-induced
      gastric erosion. Nonselective antagonist CRF receptors astressin as well as
      selective antagonists of CRF1 and CRF2 receptors (NBI 27914, 10 mg/kg or
      astressin2-B, 50 |xg/kg, respectively) aggravated ulcerogenic effect of
      indomethacin in diabetic rats. The results obtained suggest that exogenous and
      endogenous CRF may protect the gastric mucosa of diabetic rats against
      indomethacin-induced injury through CRF1 and CRF2 receptors.

PMID- 30193452
TI  - [INFARCT-LIMITING EFFECT OF ADAPTATION TO CONTINUOUS COLD EXPOSURE].
AB  - The experiments were performed on Wistar male rats, which were subjected to
      continuous cold exposure (+4  degrees C, 4 weeks). It has been established that
      this exposure is not a chronic stress. It has been shown that prolonged cold
      impact causes cold adaptation to cold and has the infarct-limi-ting effect.

PMID- 30193453
TI  - [DEPENDENCE OF FUNCTIONAL PARAMETERS OF RAT SKELETAL MUSCLE CONTRACTION FROM
      LEVEL CIRCULATING TRIIODOTHYRONINE].
AB  - In experiments on white rats with different thyroid status (thyroidectomy,
      euthyroidism, hyper- and a thyrotoxicosis) in conditions in situ the relationship
      between the severity of functional parameters of the tibialis anterior muscle and
      individual level of circulating free triiodothyronine was learnt. The latent
      period of muscle contraction, the average and maximum speed of its contraction
      were determined. A comparative quantitative analysis of the values of indicators
      of the contractile function of the tibialis anterior muscle in euthyroid and
      thyroidectomy rats allowed to evaluate the "thyroid contribution) of free
      triiodothyronine in the functional state of the native skeletal muscle, which
      formed to 15% for the latency reduction period, 12 % for the average speed of
      contractile act and 8% for of the maximum speed of muscle contraction. It is
      shown that in rats if the control group at the beginning of the scale of
      triiodothyronine concentration (2.2-4.9 pmol/L) hormone activity is expressed
      weakly, and in the range of 5.2-7.6 pmol/L is greatly increased (up to 11 times).
      It was established that the positive effect of triiodothyronine is preserved far
      beyond of the physiological norm of hormone concentration. It is allowed to speak
      about the existence of an extended corridor of hormone activity. On the base of
      the analysis of the degree of severity of the physiological parameters of the
      muscle contraction curve from circulating level of triiodothyronine in rats with
      different thyroid status (0.1-45 pmol/L) constructed of functional activity of
      free triiodothyronine. This curve consists of 7 different zones which are located
      in different sectors of the scale of concentration.

PMID- 30193454
TI  - [THE HEART ELECTRIC FIELD ON THE THORAX SURFACE OF SPORTSMEN-SWIMMERS DURING
      VENTRICULAR REPOLARIZATION UNDER ACUTE NORMOBARIC HYPOXIA].
AB  - The study of the electrical activity of the sportsmen-swimmers' heart has been
      carried out during ventricular repolarization under short-term acute moderate
      normobaric hypoxia. It was revealed that acute hypoxia leads to a significant
      decrease of the duration of the early ventricular repolarization immediately
      after hypoxic exposure, of the duration of the late repolarization - at last
      minutes. The structural change of ventricular repolarization of the heart of the
      athletes surveyed was shown based on the changes in amplitude-temporal
      characteristics of the extrema of the heart electric field during the ventricular
      repolarization of the heart upon acute hypoxic exposure.

PMID- 30193455
TI  - Dynamic Life Cycle Assessments of a Conventional Green Building and a Net Zero
      Energy Building: Exploration of Static, Dynamic, Attributional, and Consequential
      Electricity Grid Models.
AB  - Our study assesses the differences between regional average- and marginal
      electricity generation mixes as well as the variability between predicted and
      observed energy consumption of a "conventional green" Leadership in Energy and
      Environmental Design (LEED) building and a Net-Zero Energy Living Building
      (NZEB). The aim of our study was to evaluate the importance of using temporally
      resolved building-level data while capturing the dynamic effects a changing
      electrical grid has on the life cycle impacts of buildings. Two static and four
      dynamic life cycle assessment (LCA) models were evaluated for both buildings.
      Both buildings' results show that the most appropriate models ( hybrid
      consequential for the LEED Gold building, hourly consequential for the NZEB)
      significantly modified the use-phase global warming potential (GWP) impacts
      relative to the design static LCA (49% greater impact for the LEED Gold building;
      45% greater reduction for the NZEB). In other words, a "standard" LCA would
      underestimate the use phase impacts of the LEED Gold building and the benefits of
      the NZEB in the GWP category. Although the results in this paper are specific to
      two case study buildings, the methods developed are scalable and can be
      implemented more widely to improve building life cycle impact estimates.

PMID- 30193457
TI  - The Role of Public Policy in Technology Diffusion: The Case of Plug-in Electric
      Vehicles.
AB  - The plug-in electric vehicle (PEV) is regarded by many as a viable alternative to
      the internal combustion engine, so long as the radical technology is able to
      overcome technical and financial shortcomings that dictate consumer acceptance.
      States have instituted a variety of policies aimed at mitigating these
      shortcomings and simultaneously increasing consumer demand for PEV vehicles.
      Motivated by a limited body of literature on the effects of these policies, and a
      significant need for information about policy efficacy, in this study we evaluate
      the relationship between a suite of state-level policies and PEV registrations.
      Results reveal that tax credits for individuals, grants programs for charging
      infrastructure and PEV purchases, and incentives for state-owned PEVs fleets
      increase PEV registrations. The observed impact of grant incentives is mediated
      by charging capacity or, alternatively phrased, much of the influence of grants
      on registrations is through the channel of first improving the charging
      infrastructure within a state.

PMID- 30193456
TI  - Thermodynamic Stability of Flavylium Salts as a Valuable Tool To Design the
      Synthesis of A-Type Proanthocyanidin Analogues.
AB  - A convenient method to synthesize A-type proanthocyanidin analogues from
      flavylium salts and pi-nucleophiles has been developed. It was found that the
      thermodynamic stability of the starting flavylium salt, assessed by the
      measurement of the apparent acidity constant ( K'a), was the key parameter to
      design effective one-pot reactions between flavylium salts and nucleophiles such
      as phloroglucinol and (+)-catechin. When flavylium salts have a p K'a value of
      1.7 or lower, the synthesis of the corresponding 2,8-dioxabyciclo[3.3.1]nonane
      derivative was properly achieved.

PMID- 30193458
TI  - Facile Chemoselective Modification of Thio-Ethers Generates Chiral Center-Induced
      Helical Peptides.
AB  - A precisely positioned sulfimide chiral center on-tether of a thio-ether tethered
      peptide determines the peptide secondary structure by chemoselective oxaziridine
      modification. This method provides a facile way to tune peptides' secondary
      structures and biophysical properties.

PMID- 30193459
TI  - Surface-Functionalized Polystyrene Latexes Using Itaconate-Based Surfmers.
AB  - Itaconic acid was readily transformed to a series of amphiphilic diesters via
      stepwise esterification of itaconic anhydride; the diesters carry one alkyl
      (cetyl or octyl) group and either a PEG, glyceryl, or dopamine segment. These
      diesters were used as surfmers for the preparation of polystyrene (PS) emulsions,
      with the expectation that the surface of the emulsion particles would carry PEG,
      glyceryl or dopamine units. NMR spectroscopic studies revealed that the surfmers
      were covalently incorporated into the polystyrene chains; furthermore, NMR tube
      polymerization experiments also confirmed that when the PEG surfmer was used, the
      PEG segments are indeed present on the surface of the emulsion particles. The
      size of the PEGlyated PS emulsions was readily varied from 35 to 140 nm by
      changing the mole fraction of surfmer used. In the case of the glyceryl and
      dopamine carrying surfmers, an octyl unit was used as the hydrophobic segment to
      ensure appropriate hydrophobic-hydrophilic balance; it was noticed that
      significantly larger mole fractions of the surfmers were required (15-20 mol %)
      to generate stable emulsions with particle sizes of about 150 nm. The PS
      emulsions carrying dopamine units on the surface were found to adhere to glass
      surfaces; thus suggesting that such "sticky" emulsion particles could be used to
      functionalize different types of surfaces. Finally, itaconate diesters bearing
      cetyl and perfluorooctyl segments were also prepared and shown to copolymerize
      with styrene to generate fluoroalkyl-enriched PS copolymers; these were used to
      generate hydrophobic coatings, with water contact angles of over 120 degrees .
      Thus, itaconate-based surfmers are readily accessible alternatives for the
      preparation of emulsions with tailored size and surface functionality.

PMID- 30193460
TI  - Selective Permeability of Carboxysome Shell Pores to Anionic Molecules.
AB  - Carboxysomes are closed polyhedral cellular microcompartments that increase the
      efficiency of carbon fixation in autotrophic bacteria. Carboxysome shells consist
      of small proteins that form hexameric units with semipermeable central pores
      containing binding sites for anions. This feature is thought to selectively allow
      access to RuBisCO enzymes inside the carboxysome by HCO3- (the dominant form of
      CO2 in the aqueous solution at pH 7.4) but not O2, which leads to a nonproductive
      reaction. To test this hypothesis, here we use molecular dynamics simulations to
      characterize the energetics and permeability of CO2, O2, and HCO3- through the
      central pores of two different shell proteins, namely, CsoS1A of alpha
      carboxysome and CcmK4 of beta-carboxysome shells. We find that the central pores
      are in fact selectively permeable to anions such as HCO3-, as predicted by the
      model.

PMID- 30193461
TI  - Emission-Limit-Oriented Strategy To Control Atmospheric Mercury Emissions in Coal
      Fired Power Plants toward the Implementation of the Minamata Convention.
AB  - Emission limit is a significant index of pollution control in most countries.
      However, the determination of a reasonable limit value and corresponding
      supported technical paths is always a challenge during the implementation
      procedure. In this study, we developed an emission-limit-oriented strategy which
      links the emission limit with reduction amount via technical paths, so as to
      control the Hg emissions in the coal-fired power plants in China. Results
      indicate that tightening the emission limit does not always guarantee the
      reduction of Hg amounts, especially when coal consumptions keep increasing during
      the economic growth period. By comprehensively considering the feasibility of
      different technical paths, the emission limit of 5 MUg/m3 is recommended to be
      executed in 2025. Under the guidance of this limit, the reduction amount of
      emitted Hg will reach as large as 63 t during 2015-2025 by primarily using
      multipollutant control measures. During 2025-2030, both alternative energy
      measures and specific Hg removal measures will be applied to achieve the emission
      limit of 1 MUg/m3 in 2030. The assessment method developed in this study can be
      used to establish the emission-limit-oriented control strategies in other
      countries or industries, which will assist the success of the Minamata Convention
      on Mercury.

PMID- 30193462
TI  - Surfactant and Cyclodextrin Induced Vesicle to Micelle to Vesicle Transformation
      in Aqueous Medium.
AB  - The physicochemical behavior and characteristics of lipid vesicles and micelles
      in aqueous medium are greatly tuned by changing the ambient physical parameters,
      such as temperature, pH, and ionic strength. The process is also controlled by
      external additives and the nature of the surfactants. In this work, we have used
      water-soluble surfactant and cyclodextrin to transform lipid vesicles to micelles
      to vesicles without changing the physical ambience. In this regard, we have used
      a special pyrene-tagged guest compound that readily forms excimer in water and
      thus acts as a reporter for the process. Giant lipid vesicles (biological cell
      mimics) are disrupted by cationic surfactants to form mixed elongated micelles
      that transform to vesicles on applying a cyclodextrin host.

PMID- 30193463
TI  - Nitric oxide-mediated fibrinogen deposition prevents platelet adhesion and
      activation.
AB  - Thrombosis is one of the most critical challenges faced by successful clinical
      use of blood-contacting medical devices. The formation of blood clots on medical
      device surfaces is a multistep process that includes protein adsorption, platelet
      adhesion and activation, and platelet aggregation, resulting in platelet
      consumption and blockage of blood flow. Without proper treatment, thrombosis will
      lead to ultimate device failure and create complications in patients. Nitric
      oxide (NO), a small signaling molecule generated from natural endothelial cells,
      has been widely shown to reduce platelet adhesion and activation, which occurs in
      the second step of blood clotting cascade. However, few studies have investigated
      the effect of NO on protein adsorption, which is the first step of blood clotting
      cascade. In this study, the effects of NO on fibrinogen (Fb) adsorption and
      subsequent effects of Fb on platelet adhesion and activation were investigated.
      This was done by using a model NO-releasing polymer film system, plasticized
      poly(vinyl chloride) (PVC) and S-nitrosoglutathione, to examine how NO-mediated
      pre-adsorbed Fb, a major blood serum protein that initiates the blood clotting
      cascade, affects platelet adhesion and activation. The NO-releasing polymer films
      were found to increase Fb adsorption, but decrease platelet adhesion and
      activation on the surface when compared to plasticized PVC control films.
      Further, to eliminate the effects of NO on platelets, NO-releasing polymer films
      were first exposed to Fb and then incubated until all NO was released. This
      experiment isolates the effect of NO-mediated pre-adsorbed Fb on platelets in the
      absence of continuing NO release. Surprisingly, the results show that films with
      adsorbed Fb that no longer release NO continue to prevent platelet adhesion and
      activation. This study suggests that NO can affect adsorbed Fb to further prevent
      platelet adhesion and activation.

PMID- 30193464
TI  - Communication: Proton exchange in low temperature co-mixed amorphous H2O and D2O
      films: The effect of the underlying Pt(111) and graphene substrates.
AB  - Isotopic exchange reactions in mixed D2O and H2O amorphous solid water (ASW)
      films were investigated using reflection absorption infrared spectroscopy.
      Nanoscale films composed of 5% D2O in H2O were deposited on Pt(111) and graphene
      covered Pt(111) substrates. At 130 K, we find that the reaction is strongly
      dependent on the substrate with the H/D exchange being significantly more rapid
      on the Pt(111) surface than on graphene. At 140 K, the films eventually
      crystallize with the final products on the two substrates being primarily HOD
      molecule on Pt(111) and a mixture of HOD and unreacted D2O on graphene. We
      demonstrate by pre-dosing H2 and O2 on Pt(111) that the observed differences in
      reactivity on the two substrates are likely due to the formation of hydrogen ions
      at the Pt(111) surface that are not formed on graphene. Once formed the mobile
      protons move through the ASW overlayer to initiate the H/D exchange reaction.

PMID- 30193465
TI  - Communication: Optical gap in polyacetylene from a simple quantum chemistry
      exciton model.
AB  - A recent virial-theorem-based model of the singlet-triplet splitting in singly
      excited configurations [A. D. Becke, J. Chem. Phys. 148, 044112 (2018)] offers an
      accurate and economical tool for the computation of optical gaps in large
      molecules. Two single-determinant density-functional-theory calculations, one on
      the (closed-shell) ground state and another on the (restricted open-shell) HOMO 
      > LUMO triplet excited state, followed by a simple two-electron integral
      evaluation, are all we need. Here the method is used to compute the optical gaps
      of trans-polyenes containing up to 60 carbon atoms, approaching the polyacetylene
      limit. Comparisons with previous computations, and experiment, are made. We also
      explore changes of the exact-exchange mixing fraction in the underlying density
      functional. Its effect on the optical gap, and also the exciton size, is
      enormous. Thus we face the vexing, often asked, question: how much exact exchange
      should be used?

PMID- 30193466
TI  - A multi-resolution particle/fluctuating hydrodynamics model for hybrid
      simulations of liquids based on the two-phase flow analogy.
AB  - A triple-scale model of a molecular liquid, where atomistic, coarse-grained, and
      hydrodynamic descriptions of the same substance are consistently combined, is
      developed. Following the two-phase analogy method, the continuum and discrete
      particle representations of the same substance are coupled together in the
      framework of conservation laws for mass and momentum that are treated as
      effective phases of a nominally two-phase flow. The effective phase distribution,
      which governs the model resolution locally, is a user-defined function. In
      comparison with the previous models of this kind in the literature which used the
      classical Molecular Dynamics (MD) for the particulate phase, the current approach
      uses the Adaptive Resolution Scheme (AdResS) and stochastic integration to
      smoothen the particle transition from non-bonded atom dynamics to hydrodynamics.
      Accuracy and robustness of the new AdResS-Fluctuating Hydrodynamics (FH) model
      for water at equilibrium conditions is compared with the previous implementation
      of the two-phase analogy model based on the MD-FH method. To demonstrate that the
      AdResS-FH method can accurately support hydrodynamic fluctuations of mass and
      momentum, a test problem of high-frequency acoustic wave propagation through a
      small hybrid computational domain region is considered.

PMID- 30193467
TI  - Modulating charge patterning and ionic strength as a strategy to induce
      conformational changes in intrinsically disordered proteins.
AB  - We present an analytical theory to describe conformational changes as a function
      of salt for polymers with a given sequence of charges. We apply this model to
      describe Intrinsically Disordered Proteins (IDPs) by explicitly accounting for
      charged residues and their exact placement in the primary sequence while
      approximating the effect of non-electrostatic interactions at a mean-field level
      by effective short-range (two body and three-body) interaction parameters. The
      effect of ions is introduced by treating electrostatic interactions within Debye
      Huckle approximation. Using typical values of the short-range mean-field
      parameters derived from all-atom Monte Carlo simulations (at zero salt), we
      predict the conformational changes as a function of salt concentration. We notice
      that conformational transitions in response to changes in ionic strength strongly
      depend on sequence specific charge patterning. For example, globule to coil
      transition can be observed upon increasing salt concentration, in stark contrast
      to uniformly charged polyelectrolyte theories based on net charge only. In
      addition, it is possible to observe non-monotonic behavior with salt as well.
      Drastic differences in salt-induced conformational transitions is also evident
      between two doubly phosphorylated sequences-derived from the same wild type
      sequence-that only differ in the site of phosphorylation. Similar effects are
      also predicted between two sequences derived from the same parent sequence
      differing by a single site mutation where a negative charge is replaced by a
      positive charge. These effects are purely a result of charge decoration and can
      only be understood in terms of metrics based on specific placement of charges,
      and cannot be explained by models based on charge composition alone. Identifying
      sequences and hot spots within sequences-for post translational modification or
      charge mutation-using our high-throughput theory will yield fundamental insights
      into design and biological regulation mediated by phosphorylation and/or local
      changes in salt concentration.

PMID- 30193469
TI  - Temperature response of soft ionizable polymer nanoparticles.
AB  - The temperature response of luminescent ionizable polymers confined into far from
      equilibrium nanoparticles without chemical links was studied using molecular
      dynamics simulations. These nanoparticles, often referred to as polydots, are
      emerging as a promising tool for nanomedicine. Incorporating ionizable groups
      into these polymers enables biofunctionality; however, they also affect the
      delicate balance of interactions that hold these nanoparticles together. Here
      polydots formed by a model polymer dialkyl p-phenylene ethynylene with varying
      number of carboxylate groups along the polymer backbone were probed. We find that
      increasing temperature affects neutral and charged polydots differently, where
      neutral polydots exhibit a transition above which their structure becomes dynamic
      and they unravel. The dependence of the transition temperature on the surface to
      volume ratio of these polydots is much stronger than what has previously been
      observed in polymeric thin films. Charged polydots become dynamic enabling
      migration of the ionizable groups toward the particle interface, while retaining
      the overall particle shape.

PMID- 30193468
TI  - A physically grounded damped dispersion model with particle mesh Ewald summation.
AB  - Accurate modeling of dispersion is critical to the goal of predictive
      biomolecular simulations. To achieve this accuracy, a model must be able to
      correctly capture both the short-range and asymptotic behavior of dispersion
      interactions. We present here a damped dispersion model based on the overlap of
      charge densities that correctly captures both regimes. The overlap damped
      dispersion model represents a classical physical interpretation of dispersion:
      the interaction between the instantaneous induced dipoles of two distinct charge
      distributions. This model is shown to be an excellent fit with symmetry adapted
      perturbation theory dispersion energy calculations, yielding an RMS error on the
      S101x7 database of 0.5 kcal/mol. Moreover, the damping function used in this
      model is wholly derived and parameterized from the electrostatic dipole-dipole
      interaction, making it not only physically grounded but transferable as well.

PMID- 30193470
TI  - Investigating the effective interaction between silica colloidal particles near
      the critical point of a binary solvent by small angle neutron scattering.
AB  - An effective attractive potential can be introduced between colloidal particles
      dispersed in a binary solvent when the solvent condition approaches its demixing
      temperatures. Despite the debate of the physical origins of this effective
      attraction, it is widely termed as the critical Casimir force and is believed to
      be responsible for the colloidal stability in a wide range of particle
      concentration at both critical and near-critical solvent concentrations. Here, we
      study the effective attraction and equilibrium phase transition of charged
      spherical silica particles in the binary solvent of 2,6-lutidine and water as a
      function of the particle volume fraction and temperature at the critical solvent
      concentration. By analyzing our small angle neutron scattering (SANS) data, we
      found that at a relatively small particle volume fraction, the density
      fluctuation introduced attraction between silica particles can be satisfactorily
      explained by the function form commonly used for the critical Casimir
      interaction. However, at large silica particle volume fractions, an additional
      long range attraction has to be introduced to satisfactorily fit our SANS data
      and explain the large shift of the phase transition temperature. Therefore, while
      at relatively low volume fractions, the solvent introduced attraction may be
      dominated by the critical Casimir force, the physical mechanism of the effective
      attraction at large particle volume fractions seems to be different from the
      critical Casimir force. Furthermore, the range of this long range attraction is
      consistent with a recently proposed new theory, where the attraction can be
      introduced by the solvent capillary condensation between particles. We also
      demonstrate that the reduced second virial coefficient close to the particle
      phase transition is similar to the values of the binodal transition of the sticky
      hard sphere system.

PMID- 30193471
TI  - Toward quantum-chemical method development for arbitrary basis functions.
AB  - We present the design of a flexible quantum-chemical method development
      framework, which supports employing any type of basis function. This design has
      been implemented in the light-weight program package molsturm, yielding a basis
      function-independent self-consistent field scheme. Versatile interfaces, making
      use of open standards like python, mediate the integration of molsturm with
      existing third-party packages. In this way, both rapid extension of the present
      set of methods for electronic structure calculations as well as adding new basis
      function types can be readily achieved. This makes molsturm well-suitable for
      testing novel approaches for discretising the electronic wave function and allows
      comparing them to existing methods using the same software stack. This is
      illustrated by two examples, an implementation of coupled-cluster doubles as well
      as a gradient-free geometry optimisation, where in both cases, arbitrary basis
      functions could be used. molsturm is open-sourced and can be obtained from
      http://molsturm.org.

PMID- 30193472
TI  - Characterization of the vibrational properties of copper difluoride anion and
      neutral ground states via direct and indirect photodetachment spectroscopy.
AB  - Photoelectron spectra of 63CuF2- are reported at wavelengths 310 nm, 346.6 nm,
      and 350.1 nm, obtained via velocity map imaging. The photoelectron angular
      distributions allow for the unambiguous assignment of a 2Sigmag+ neutral CuF2
      ground state. Vibrational analysis of the direct detachment transitions in the
      spectra enables accurate determination of the anion and neutral bond length
      difference (0.073 A), adiabatic electron affinity of CuF2 (3.494 eV) and
      symmetric stretching (500 cm-1, anion, and 630 cm-1, neutral) and antisymmetric
      stretching (610 cm-1, anion, and 782 cm-1 neutral) frequencies of the ground
      electronic states. Strongly photon energy dependent intensities are also observed
      for select transitions. Equation-of-motion coupled-cluster singles and doubles
      calculations augmented by a complex absorbing potential reveal a metastable 1Pig
      anion state which is optically accessible due to Renner-Teller coupling.
      Mediation of the detachment process by this state allows measurement of the
      bending frequencies (177 cm-1, anion, and 200 cm-1, neutral) completing the
      inventory of experimentally measured vibrational properties of the ground
      electronic states.

PMID- 30193473
TI  - Harmonic surface mapping algorithm for fast electrostatic sums.
AB  - We propose a harmonic surface mapping algorithm (HSMA) for electrostatic pairwise
      sums of an infinite number of image charges. The images are induced by point
      sources within a box due to a specific boundary condition which can be non
      periodic. The HSMA first introduces an auxiliary surface such that the
      contribution of images outside the surface can be approximated by the least
      squares method using spherical harmonics as basis functions. The so-called
      harmonic surface mapping is the procedure to transform the approximate solution
      into a surface charge and a surface dipole over the auxiliary surface, which
      becomes point images by using numerical integration. The mapping procedure is
      independent of the number of the sources and is considered to have a low
      complexity. The electrostatic interactions are then among those charges within
      the surface and at the integration points, which are all the forms of Coulomb
      potential and can be accelerated straightforwardly by the fast multipole method
      to achieve linear scaling. Numerical calculations of the Madelung constant of a
      crystalline lattice, electrostatic energy of ions in a metallic cavity, and the
      time performance for large-scale systems show that the HSMA is accurate and fast,
      and thus is attractive for many applications.

PMID- 30193474
TI  - Ring-opening attachment as an explanation for the long lifetime of the
      octafluorooxolane anion.
AB  - Octafluorooxalane, C4F8O, has recently attracted attention as a possible
      replacement of SF6 in high voltage insulation, and its reactivity with respect to
      free-electron attachment was investigated by mass spectrometry. The most intense
      signal peaks at 0.9 eV and corresponds to the parent anion, C4F8O-; fragments
      stemming from complex breakup reactions are detected starting above ~1.6 eV.
      Since parent anions in free-electron attachment are normally associated with
      threshold attachment or an embedding environment allowing excess energy
      deposition, this observation is highly unusual. Based on density functional
      calculations, it was nevertheless interpreted as attachment followed by
      intermolecular-vibrational-relaxation. Here, electron-attachment to
      octafluorooxalane is studied computationally. First, the electron affinity (EA)
      is characterized using density functionals and ab initio methods. Moreover, the
      negative vertical EA is estimated by extrapolating electron binding energies
      computed in the vicinity of C4F8O- to the geometry of neutral octafluorooxalane.
      Then, alternative explanations for the 0.9 eV peak are considered. Specifically,
      a ring-opening reaction that yields a distonic isomer of C4F8O- is identified.
      Our analysis reveals that the chain isomer possesses many conformers, all of
      which are considerably more stable than the ring isomer, and that the time scale
      for the unimolecular ring opening reaction is significantly faster than 1 MUs.
      Thus, at the experimental energy, the ring isomer of C4F8O- is predicted to
      convert practically completely into the chain isomer, and we argue that the long
      lifetime and the peak position are effectively determined by the properties of
      the ring-opening transition state.

PMID- 30193475
TI  - The electric double layer at metal-water interfaces revisited based on a charge
      polarization scheme.
AB  - The description of electrode-electrolyte interfaces is based on the concept of
      the formation of an electric double layer. This concept was derived from
      continuum theories extended by introducing point charge distributions. Based on
      ab initio molecular dynamics simulations, we analyze the electric double layer in
      an approach beyond the point charge scheme by instead assessing charge
      polarizations at electrochemical metal-water interfaces from first principles. We
      show that the atomic structure of water layers at room temperature leads to an
      oscillatory behavior of the averaged electrostatic potential. We address the
      relation between the polarization distribution at the interface and the extent of
      the electric double layer and subsequently derive the electrode potential from
      the charge polarization.

PMID- 30193476
TI  - A methodology to calculate small-angle scattering profiles of macromolecular
      solutions from molecular simulations in the grand-canonical ensemble.
AB  - The theoretical framework to evaluate small-angle scattering (SAS) profiles for
      multi-component macromolecular solutions is re-examined from the standpoint of
      molecular simulations in the grand-canonical ensemble, where the chemical
      potentials of all species in solution are fixed. This statistical mechanical
      ensemble resembles more closely scattering experiments, capturing concentration
      fluctuations that arise from the exchange of molecules between the scattering
      volume and the bulk solution. The resulting grand-canonical expression relates
      scattering intensities to the different intra- and intermolecular pair
      distribution functions, as well as to the distribution of molecular
      concentrations on the scattering volume. This formulation represents a
      generalized expression that encompasses most of the existing methods to evaluate
      SAS profiles from molecular simulations. The grand-canonical SAS methodology is
      probed for a series of different implicit-solvent, homogeneous systems at
      conditions ranging from dilute to concentrated. These systems consist of
      spherical colloids, dumbbell particles, and highly flexible polymer chains.
      Comparison of the resulting SAS curves against classical methodologies based on
      either theoretical approaches or canonical simulations (i.e., at a fixed number
      of molecules) shows equivalence between the different scattering intensities so
      long as interactions between molecules are net repulsive or weakly attractive. On
      the other hand, for strongly attractive interactions, grand-canonical SAS
      profiles deviate in the low- and intermediate-q range from those calculated in a
      canonical ensemble. Such differences are due to the distribution of molecules
      becoming asymmetric, which yields a higher contribution from configurations with
      molecular concentrations larger than the nominal value. Additionally, for
      flexible systems, explicit discrimination between intra- and inter-molecular SAS
      contributions permits the implementation of model-free, structural analysis such
      as Guinier's plots at high molecular concentrations, beyond what the traditional
      limits are for such analysis.

PMID- 30193478
TI  - Perspective: The development and applications of H Rydberg atom translational
      spectroscopy methods.
AB  - Determining the product velocities offers one of the most direct and penetrating
      experimental probes of the dynamics of gas phase molecular photodissociation and
      bimolecular collision processes and provides an obvious point of contact with
      theoretical molecular dynamics simulations, potential energy surfaces, and non
      adiabatic couplings between such surfaces. This perspective traces the
      development of the H Rydberg atom translational spectroscopy technique from a
      serendipitous first encounter through to the present, highlights the advances
      that make it the method of choice for studying many benchmark photofragmentation
      and photoinduced collision processes that yield H (or D) atoms amongst the
      products, and anticipates some future opportunities afforded by the technique.

PMID- 30193477
TI  - Advances in milestoning. II. Calculating time-correlation functions from
      milestoning using stochastic path integrals.
AB  - In the milestoning framework, and more generally in related transition interface
      sampling schemes, one significantly enhances the calculation of relaxation rates
      for complex equilibrium kinetics from molecular dynamics simulations between the
      milestones or interfaces. The goal of the present paper is to advance milestoning
      applications into the realm of non-equilibrium statistical mechanics, in
      particular, to calculate entire time correlation functions. In order to
      accomplish this, we introduce a novel methodology for obtaining the flux through
      a given milestone configuration as a function of both time and initial
      configuration and build upon it with a novel formalism describing autocorrelation
      for Langevin motion in a discrete configuration space. The method is then applied
      to three different test systems: a harmonic oscillator, which we solve
      analytically, a two-well potential, which is solved numerically, and an atomistic
      molecular dynamics simulation of alanine dipeptide.

PMID- 30193479
TI  - Stress auto-correlation tensor in glass-forming isothermal fluids: From viscous
      to elastic response.
AB  - We develop a generalized hydrodynamic theory, which can account for the build-up
      of long-ranged and long-lived shear stress correlations in supercooled liquids as
      the glass transition is approached. Our theory is based on the decomposition of
      tensorial stress relaxation into fast microscopic processes and slow dynamics due
      to conservation laws. In the fluid, anisotropic shear stress correlations arise
      from the tensorial nature of stress. By approximating the fast microscopic
      processes by a single relaxation time in the spirit of Maxwell, we find
      viscoelastic precursors of the Eshelby-type correlations familiar in an elastic
      medium. The spatial extent of shear stress fluctuations is characterized by a
      correlation length xi which grows like the viscosity eta or time scale tau ~ eta,
      whose divergence signals the glass transition. In the solid, the correlation
      length is infinite and stress correlations decay algebraically as r-d in d
      dimensions.

PMID- 30193480
TI  - Advances in milestoning. I. Enhanced sampling via wind-assisted reweighted
      milestoning (WARM).
AB  - The milestoning algorithm of Elber and co-workers creates a framework for
      computing the time scale of processes that are too long and too complex to be
      studied using simply brute force simulations. The fundamental objects involved in
      the milestoning algorithm are the first passage time distributions KAB (tau)
      between adjacent conformational milestones A and B. The method proposed herein
      aims to further enhance milestoning (or other interface based sampling methods)
      by employing an artificially applied force, akin to a wind that blows the
      trajectories from their initial to their final states, and by subsequently
      applying corrective weights to the trajectories to yield the true first passage
      time distributions KAB (tau) in a fraction of the computation time required for
      unassisted calculations. The re-weighting method is rooted in the formalism of
      stochastic path integrals. The theoretical basis for the technique and numerical
      examples are presented.

PMID- 30193481
TI  - Linear absorption spectrum of a quantum two-dimensional rotator calculated using
      a rotationally invariant system-bath Hamiltonian.
AB  - We consider a two-dimensional rigid rotator system coupled to a two-dimensional
      heat bath. The Caldeira-Leggett (Brownian) model for the rotator and the spin
      Boson model have been used to describe such systems, but they do not possess
      rotational symmetry, and they cannot describe the discretized rotational bands in
      absorption and emission spectra that have been found experimentally. Here, to
      address this problem, we introduce a rotationally invariant system-bath (RISB)
      model that is described by two sets of harmonic-oscillator baths independently
      coupled to the rigid rotator as sine and cosine functions of the rotator angle.
      Due to a difference in the energy discretization of the total Hamiltonian, the
      dynamics described by the RISB model differ significantly from those described by
      the rotational Caldeira-Legget model, while both models reduce to the Langevin
      equation for a rotator in the classical limit. To demonstrate this point, we
      compute the rotational absorption spectrum defined by the linear response
      function of a rotator dipole. For this purpose, we derive a quantum master
      equation for the RISB model in the high-temperature Markovian case. We find that
      the spectral profiles of the calculated signals exhibit a transition from
      quantized rotational bands to a single peak after spectrum collapse. This is a
      significant finding because previous approaches cannot describe such phenomena in
      a unified manner.

PMID- 30193483
TI  - Fitting a round peg into a round hole: Asymptotically correcting the generalized
      gradient approximation for correlation.
AB  - We consider the implications of the Lieb-Simon limit for correlation in density
      functional theory. In this limit, exemplified by the scaling of neutral atoms to
      large atomic number, local density approximation (LDA) becomes relatively exact,
      and the leading correction to this limit for correlation has recently been
      determined for neutral atoms. We use the leading correction to the LDA and the
      properties of the real-space cutoff of the exchange-correlation hole to design,
      based upon Perdew-Burke-Ernzerhof (PBE) correlation, an asymptotically corrected
      generalized gradient approximation (acGGA) correlation which becomes more
      accurate per electron for atoms with increasing atomic number. When paired with a
      similar correction for exchange, this acGGA satisfies more exact conditions than
      PBE. Combined with the known rs -dependence of the gradient expansion for
      correlation, this correction accurately reproduces correlation energies of closed
      shell atoms down to Be. We test this acGGA for atoms and molecules, finding
      consistent improvement over PBE but also showing that optimal global hybrids of
      acGGA do not improve upon PBE0 and are similar to meta-GGA values. We discuss the
      relevance of these results to Jacob's ladder of non-empirical density functional
      construction.

PMID- 30193482
TI  - Acceleration of DNA melting kinetics using alternating electric fields.
AB  - We verify both theoretically and by simulation that an AC electric field, with a
      frequency much higher than the dissociation rate, can significantly accelerate
      the dissociation rate of biological molecules under isothermal conditions. The
      cumulative effect of the AC field is shown to break a key bottleneck by reducing
      the entropy (and increasing the free energy of the local minimum) via the
      alignment of the molecular dipole with the field. For frequencies below a
      resonant frequency which corresponds to the inverse Debye dipole relaxation time,
      the dissociation rate can be accelerated by a factor that scales as
      omega(epsilon'(omega)-1)E02 , where omega is the field frequency, E0 is the field
      amplitude, and epsilon'(omega) is the frequency-dependent real permittivity of
      the molecule. At large amplitudes, we find that the accelerated melting rate
      becomes universal, independent of duplex size and sequence, which is in drastic
      contrast to Ohmic thermal melting. We confirm our theory with isothermal all
      atomic molecular dynamics simulation of short DNA duplexes with known melting
      rates, demonstrating several orders in enhancement with realistic fields.

PMID- 30193484
TI  - Hydrogen motional disorder in crystalline iron group chloride dihydrates.
AB  - The principal components and the relative orientation of the 2H paramagnetic
      shift and quadrupolar coupling tensors have been measured for the MCl2.2D2O
      family of compounds, M = Mn, Fe, Co, Ni, and Cu, using the two-dimensional
      shifting-d echo nuclear magnetic resonance experiment in order to determine (1)
      the degree of unpaired electron delocalization and (2) the number and location of
      crystallographically distinct hydrogen sites around oxygen and their fractional
      occupancies. Expressions for the molecular susceptibility of 3d ion systems,
      where the spin-orbit coupling is a weak perturbation onto the crystal field, are
      derived using the generalized Van Vleck equation and used to predict molecular
      susceptibilities. These predicted molecular susceptibilities are combined with
      various point dipole source configurations modeling unpaired electron
      delocalization to predict 2H paramagnetic shift tensors at potential deuterium
      sites. The instantaneous deuterium quadrupolar coupling and shift tensors are
      then combined with parameterized motional models, developed for trigonally (M =
      Mn, Fe, Co, and Cu) and pyramidally (M = Ni) coordinated D2O ligands, to obtain
      the best fit of the experimental 2D spectra. Dipole sources placed onto metal
      nuclei with a small degree of delocalization onto the chlorine ligands yield good
      agreement with the experiment for M = Mn, Fe, Co, and Ni, while good agreement
      for CuCl2.2D2O is obtained with additional delocalization onto the oxygen. Our
      analysis of the salts with trigonally coordinated water ligands (M = Mn, Fe, Co,
      and Cu) confirms the presence of bisector flipping and the conclusions from
      neutron scattering measurements that hydrogen bonding to chlorine on two adjacent
      chains leads to the water molecule in the [M(D2O)2Cl4] cluster being nearly
      coplanar with O-M-Cl involving the shortest metal-chlorine bonds of the cluster.
      In the case of NiCl2.2D2O, the experimental parameters were found to be
      consistent with a motional model where the D2O ligands are pyramidally
      coordinated to the metal and undergo bisector flipping while the water ligand
      additionally hops between two orientations related by a 120 degrees  rotation
      about the Ni-O bond axis. The position of the three crystallographically distinct
      hydrogen sites in the unit cell was determined along with fractional occupancies.
      This restricted water ligand motion is likely due to van der Waals interactions
      and is concerted with the motion of neighboring ligands.

PMID- 30193485
TI  - Correspondence between light-absorption spectrum and nonequilibrium work
      distribution as a mean to access free energy differences between electronic
      states.
AB  - The problem of recovering the free energy difference between two electronic
      states has been investigated by Frezzato [Chem. Phys. Lett. 533, 106 (2012)],
      exploring the equivalence between light-absorption spectra and work distribution,
      hence opening to the application of a spectroscopic version of the Jarzynski
      equality (JE) [Phys. Rev. Lett. 78, 2690 (1997)]. Here, assuming the validity of
      the time-dependent perturbation theory, we demonstrate that such equivalence does
      not lead to the known form of the JE. This is ascribed to the fact that light
      absorption processes cannot be described as stochastic processes. To emphasize
      such an aspect, we devise a stochastic model for the UV-vis (ultraviolet and
      visible) absorption, suitable for determining the free energy difference between
      two generic quantum manifolds in a JE-like fashion. However, the model would
      require explicit knowledge of the transition dipole moments, which are in general
      not available. Nonetheless, we derive a spectroscopic version of the JE that
      allows us to recover the free energy difference between the ground and an excited
      electronic state when the latter state is the only one observed in the spectrum.

PMID- 30193486
TI  - Energy dependent parity-pair behavior in NO + He collisions.
AB  - Colliding molecules behave fundamentally differently at high and low collision
      energies. At high energies, a collision can be described to a large extent using
      classical mechanics, and the scattering process can be compared to a billiard
      ball-like collision. At low collision energies, the wave character of the
      collision partners dominates, and only quantum mechanics can predict the outcome
      of an encounter. It is, however, not so clear how these limits evolve into each
      other as a function of the collision energy. Here, we investigate and visualize
      this evolution using a special feature of the differential cross sections for
      inelastic collisions between NO radicals and He atoms. The so-called "parity
      pair" transitions have similar differential cross sections at high collision
      energies, whereas their cross sections are significantly different in the quantum
      regime at low energies. These transitions can be used as a probe for the quantum
      nature of the collision process. The similarity of the parity-pair differential
      cross sections at high energies could be theoretically explained if the first
      order Born approximation were applicable. We found, however, that the anisotropy
      of the NO-He interaction potential is too strong for the first-order Born
      approximation to be valid, so higher-order perturbations must be taken into
      account.

PMID- 30193487
TI  - Complex momentum behavior of electronic excitations in beta-CuPc.
AB  - The electronic excitation spectrum of beta-CuPc has been investigated using
      electron energy-loss spectroscopy in transmission. Our results demonstrate a
      rather strong momentum dependence of the lowest exciton features. Both main
      components show a negative dispersion, and the momentum dependence indicates that
      this negative dispersion is parallel to the molecular stacks in beta-CuPc. In
      addition, the spectral shape also varies upon increasing momentum transfer
      indicating a particular momentum dependence of the inter-molecular interactions.

PMID- 30193488
TI  - Breakdown of Carr-Purcell Meiboom-Gill spin echoes in inhomogeneous fields.
AB  - The Carr-Purcell Meiboom-Gill (CPMG) experiment has been used for decades to
      measure nuclear-spin transverse (T2) relaxation times. In the presence of
      magnetic field inhomogeneities, the limit of short interpulse spacings yields the
      intrinsic T2 time. Here, we show that the signal decay in such experiments
      exhibits fundamentally different behaviors between liquids and gases. In gases,
      the CPMG unexpectedly fails to eliminate the inhomogeneous broadening due to the
      non-Fickian nature of the motional averaging.

PMID- 30193489
TI  - Lipids with bulky head groups generate large membrane curvatures by small
      compositional asymmetries.
AB  - Glycolipids such as GM1 have bulky head groups consisting of several
      monosaccharides. When these lipids are added to phospholipid bilayers, they
      generate large membrane curvatures even for small compositional asymmetries
      between the two leaflets of the bilayers. On the micrometer scale, these bilayer
      asymmetries lead to the spontaneous tubulation of giant vesicles as recently
      observed by optical microscopy. Here, we study these mixed membranes on the
      nanometer scale using coarse-grained molecular simulations. The membrane
      composition is defined by the mole fractions phi1 and phi2 of the large-head
      lipid in the two leaflets of the bilayer. Symmetric membranes are obtained for
      phi1 = phi2 = phile, and asymmetric ones for phi1 ? phi2. In both cases, we
      compute the density and stress profiles across the membranes. The stress profiles
      are used to identify the tensionless states of the membranes. Symmetric and
      tensionless bilayers are found to be stable within the whole composition range 0
      <= phile <= 1. For these symmetric bilayers, both the area compressibility
      modulus and the bending rigidity are found to vary non-monotonically with the
      leaflet mole fraction phile. For asymmetric bilayers, we compute the product of
      bending rigidity and spontaneous curvature from the first moment of the stress
      profile and determine the bending rigidities of the asymmetric membranes using
      the phile-dependent rigidities of the single leaflets. When we combine these
      results, the compositional asymmetry phi1 - phi2 is found to generate the
      spontaneous curvature (phi1 - phi2)/(0.63 lme) with the membrane thickness lme ?
      4 nm. Therefore, the spontaneous curvature increases linearly with the
      compositional asymmetry. Furthermore, the small compositional asymmetry phi1 -
      phi2 = 0.04 leads to the large spontaneous curvature 1/(63 nm) and the increased
      asymmetry phi1 - phi2 = 0.2 generates the huge spontaneous curvature 1/(13 nm).
      These large values of the spontaneous curvature will facilitate future simulation
      studies of various membrane processes such as bud formation and nanoparticle
      engulfment.

PMID- 30193490
TI  - Optimizing co-operative multi-environment dynamics in a dark-state-enhanced
      photosynthetic heat engine.
AB  - We analyze the role of coherent, non-perturbative system-bath interactions in a
      photosynthetic heat engine. Using the reaction-coordinate formalism to describe
      the vibrational phonon-environment in the engine, we analyze the efficiency
      around an optimal parameter regime predicted in earlier studies. We show that, in
      the limit of high-temperature photon irradiation, the phonon-assisted population
      transfer between bright and dark states is suppressed due to dephasing from the
      photon environment, even in the Markov limit where we expect the influence of
      each bath to have an independent and additive effect on the dynamics.
      Manipulating the phonon bath properties via its spectral density enables us to
      identify both optimal low- and high-frequency regimes where the suppression can
      be removed. This suppression of transfer and its removal suggests that it is
      important to consider carefully the non-perturbative and cooperative effects of
      system-bath environments in designing artificial photosynthetic systems and also
      that manipulating inter-environmental interactions could provide a new
      multidimensional "lever" by which photocells and other types of quantum devices
      can be optimized.

PMID- 30193491
TI  - Heteronuclear molecules from matrix isolation sublimation and atomic diffusion.
AB  - We demonstrate the production of cryogenic beams of heteronuclear molecules from
      the matrix isolation sublimation (MISu) technique. A sapphire mirror serves as a
      substrate whereupon a solid Ne matrix is grown. Atoms of Li, H, Ca, and C are
      implanted into the matrix via subsequent laser ablation of different solid
      precursors such as Ca, Li, LiH, and graphite. The matrix is sublimated into
      vacuum generating a cryogenic beam of Ne carrying the previously isolated neutral
      atomic and molecular species. A compact and low energy electron source and time
      of-flight mass spectrometer was designed to fit this system at low temperature.
      With electron ionization time-of-flight mass spectrometry, we analyze the species
      coming from MISu and demonstrate the formation of heteronuclear molecules in the
      matrix. In this first study, we produced LiCa from the sequential implantation of
      Li and Ca into the matrix and some clusters of CnLim after Li and C ablation.
      Also from ablation of a single LiH pellet, we observed clusters of LinHm. This
      novel technique opens up the opportunity to generate cryogenic beams of different
      molecules for precision physics and chemistry studies. Laser or microwave high
      resolution spectroscopy of a molecular beam benefits from low translational and
      rovibrational temperatures and forward velocities, such as the ones produced in
      this technique. Toward the prospect of enhancing the molecular formation, we
      introduce a new method to study the atomic diffusion of Li and Ca in the Ne
      matrix via laser spectroscopy during sublimation. We estimate a small diffusion
      coefficient at 7 K, but a surprisingly linear atomic dispersion during
      sublimation. The method is extensive to other species and matrices.

PMID- 30193492
TI  - Maxwell-Boltzmann versus non-ergodic events in the velocity distribution of water
      molecules evaporated from protonated water nanodroplets.
AB  - Measurement of velocity distributions of evaporated water monomers from small
      mass- and energy-selected protonated water clusters allows probing the extent of
      thermalization after excitation of these ultimately small nanodroplets.
      Electronic excitation of a molecule in the cluster is here induced by a single
      collision with an argon atom in the keV energy range. The measured velocity
      distributions of the departing neutral molecules exhibit bimodal shapes with a
      lower-velocity part consistent with a complete redistribution of the deposited
      energy in the entire cluster and a higher-velocity contribution corresponding to
      evaporation before complete energy redistribution. Statistical molecular dynamics
      calculations reproduce the bimodal shape of the velocity distributions by
      assuming an initial spreading of the excitation energy among all modes, thereby
      reproducing the lower velocity contribution of the distribution. By contrast,
      assuming the deposited energy to be initially localized among the modes of a
      single molecule leads to calculated distributions with two components whose shape
      is in accordance with the experimental results. The characteristics and the
      relative abundance of these two contributions in the velocity distributions
      obtained are presented and discussed as a function of the number of molecules (n
      = 2-10) in the ionized nanodroplet H+(H2O) n .

PMID- 30193493
TI  - Linear rheology of reversibly cross-linked biopolymer networks.
AB  - We suggest a simple model for reversible cross-links, binding, and unbinding
      to/from a network of semiflexible polymers. The resulting frequency dependent
      response of the network to an applied shear is calculated via Brownian dynamics
      simulations. It is shown to be rather complex with the time scale of the linkers
      competing with the excitations of the network. If the lifetime of the linkers is
      the longest time scale, as is indeed the case in most biological networks, then a
      distinct low frequency peak of the loss modulus develops. The storage modulus
      shows a corresponding decay from its plateau value, which for irreversible cross
      linkers extends all the way to the static limit. This additional relaxation
      mechanism can be controlled by the relative weight of reversible and irreversible
      linkers.

PMID- 30193494
TI  - The ring-opening channel and the influence of Rydberg states on the excited state
      dynamics of furan and its derivatives.
AB  - One important relaxation pathway for photo-excited five-membered heterocyclic
      organic molecules is ring-opening via a dissociative pisigma* state. In this
      study, we investigate the influence of this pathway in furan and several
      hydrogenated and methylated derivatives by combining time-resolved photoelectron
      spectroscopy with time-dependent density functional theory and coupled cluster
      calculations. We find strong experimental evidence that the ring-opening channel
      is the major relaxation channel in furan, 2,3-dihydrofuran, and 2-methylfuran (2
      MF). In 2,5-dimethylfuran (25-DMF), however, we observe that the molecules relax
      either via a pi3s Rydberg state or through a direct return to the ground state by
      undergoing ring-puckering motions. From the supporting calculations, for 2-MF and
      25-DMF, we predict that there is strong mixing between the pisigma* state and the
      pi3s Rydberg state along the ring opening pathway. However, in 25-DMF, no
      crossing between the pisigma*/pi3s state and the initially excited pipi* state
      can be found along the ring opening coordinate, effectively blocking this
      channel.

PMID- 30193495
TI  - A unifying identity for the work of cluster formation in heterogeneous and
      homogeneous nucleation theory.
AB  - A unifying identity is derived relating the reversible work of cluster formation
      (W) and its molecular number content (n) and surface work (Phi) components, each
      ratioed to the corresponding values for a spherical capillary drop of critical
      size in classical nucleation theory. The result is a relationship that connects
      these ratios: fW = -2fN + 3fS, where fW = W/W*CNT, fN = n/n*CNT, and fS =
      Phi/Phi*CNT. Shown to generalize two early thermodynamic relationships of Gibbs,
      the new result is demonstrated here for Fletcher's model of heterogeneous
      nucleation, resulting in a unified treatment of condensation on flat and curved
      substrates and smooth passage to the homogeneous limit. Additional applications
      are made to clusters of non-critical as well as critical size and to a molecular
      based extension of classical nucleation theory based on the Kelvin relation. The
      new identity serves as a consistency check on complicated theoretical expressions
      and numerical calculations and can be used to guide the construction of theory
      and interpretation of measurements.

PMID- 30193496
TI  - Multi-scale simulations of polymeric nanoparticle aggregation during rapid
      solvent exchange.
AB  - Using a multi-scale approach which combines both molecular dynamics (MD) and
      kinetic Monte Carlo (KMC) simulations, we study a simple and scalable method for
      fabricating charge-stabilized nanoparticles through a rapid solvent exchange,
      i.e., Flash NanoPrecipitation (FNP). This multi-scale approach is based on
      microscopic information from MD simulations and uses a KMC algorithm to access
      macroscopic length- and time scales, which allows direct comparison with
      experiments and quantitative predictions. We find good agreement of our
      simulation results with the experiments. In addition, the model allows us to
      understand the aggregation mechanism on both microscopic and macroscopic levels
      and determine dependence of nanoparticle size on processing parameters such as
      the mixing rate and the polymer feed concentration. It also provides an estimate
      for the characteristic growth time of nanoparticles in the FNP process. Our
      results thus give useful insights into tailoring the FNP technique for
      fabricating nanoparticles with a specific set of desirable properties for various
      applications.

PMID- 30193497
TI  - Communication: Multi-mass velocity map imaging study of the ultraviolet
      photodissociation of dimethyl sulfide using single photon ionization and a PImMS2
      sensor.
AB  - This study of the photodissociation of dimethyl sulfide at lambda = 227.5 nm
      demonstrates the opportunities (and some of the challenges) of product detection
      using vacuum ultraviolet photoionization combined with recently developed multi
      mass imaging methods. The capability of imaging different charged products
      simultaneously allows determination of the primary fragmentation dynamics
      through, for example, product fragment momentum and angular distribution matching
      and reveals potential complications from dissociative ionization, product
      alignment-dependent photoionization probabilities, and the effects of space
      charging.

PMID- 30193498
TI  - The pressure in interfaces having cylindrical geometry.
AB  - While much work has been reported on the statistical mechanics and molecular
      simulation of interfaces of planar and spherical geometries, very little has been
      published on the interfaces of cylindrical geometry. The cylindrical geometry is
      important for the study of cylindrical micelles and particularly for nano-phases
      confined within cylindrical pores since the most well-defined porous materials
      (e.g., carbon and silicon nanotubes, SBA-15 and KIT-6 silicas) that are presently
      available are of this geometry. In this work, we derive the statistical
      mechanical equations for the pressure tensor for an interfacial region of
      cylindrical geometry via the virial route and for the condition of mechanical
      (hydrostatic) equilibrium. We also report the equation for the surface tension
      via the mechanical route. Monte Carlo and molecular dynamics simulation results
      are obtained for two example systems involving a fluid nano-phase of Lennard
      Jones argon: a gas-liquid interface of cylindrical geometry and a confined nano
      phase within a cylindrical carbon pore. All three diagonal elements of the
      pressure tensor are reported in each case, the component normal to the interface,
      PN = Prhorho , and the two tangential components PTphi = Pphiphi and PTz = Pzz ,
      where (rho, z, phi) are the usual cylindrical polar coordinates. For the
      cylindrical pore, the tangential pressures, Pphiphi and Pzz , show strong
      compression in the adsorbed layers, as has been found in slit-shaped and
      spherical pores.

PMID- 30193499
TI  - A highly accurate ab initio dipole moment surface for the ground electronic state
      of water vapour for spectra extending into the ultraviolet.
AB  - A new global and highly accurate ab initio dipole moment surface (DMS) for water
      vapour is presented. This DMS is based on a set of 17 628 multi-reference
      configuration interaction data points that were calculated with the aug-cc-pCV6Z
      basis set with the Douglas-Kroll-Hess Hamiltonian; tests are performed at several
      other levels of ab initio theory. This new "CKAPTEN" DMS improves agreement with
      recent experimental measurements compared with previous models that poorly
      predicted some bands in the infrared while also maintaining or improving on the
      agreement for all remaining strong lines. For high overtones located in both the
      visible and the near ultraviolet regions, our predicted intensities all lie
      within 10% of recent atmospheric observations. A crossing of energy levels in the
      nu1 fundamental and 2nu2 states is seen to offset transition intensities in the
      nu1 fundamental band; residual inaccuracies within the potential energy surface
      used is the cause of this problem.

PMID- 30193500
TI  - Communication: A mean field platform for excited state quantum chemistry.
AB  - We present a mean field theory for excited states that is broadly analogous to
      ground state Hartree-Fock theory. Like Hartree-Fock, our approach is
      deterministic, state-specific, applies a variational principle to a minimally
      correlated ansatz, produces energy stationary points, relaxes the orbital basis,
      has a Fock-build cost-scaling, and can serve as the foundation for correlation
      methods such as perturbation theory and coupled cluster theory. To emphasize this
      last point, we pair our mean field approach with an excited state analog of
      second order Moller-Plesset theory and demonstrate that in water, formaldehyde,
      neon, and stretched lithium fluoride, the resulting accuracy far exceeds that of
      configuration interaction singles and rivals that of equation of motion coupled
      cluster.

PMID- 30193501
TI  - Stability conditions and local minima in multicomponent Hartree-Fock and density
      functional theory.
AB  - Multicomponent quantum chemistry allows the quantum mechanical treatment of
      electrons and specified protons on the same level. Typically the goal is to
      identify a self-consistent-field (SCF) solution that is the global minimum
      associated with the molecular orbital coefficients of the underlying Hartree-Fock
      (HF) or density functional theory (DFT) calculation. To determine whether the
      solution is a minimum or a saddle point, herein we derive the stability
      conditions for multicomponent HF and DFT in the nuclear-electronic orbital (NEO)
      framework. The gradient is always zero for an SCF solution, whereas the Hessian
      must be positive semi-definite for the solution to be a minimum rather than a
      saddle point. The stability matrices for NEO-HF and NEO-DFT have the same matrix
      structures, which are identical to the working matrices of their corresponding
      linear response time-dependent theories (NEO-TDHF and NEO-TDDFT) but with a
      different metric. A negative eigenvalue of the stability matrix is a necessary
      but not sufficient condition for the corresponding NEO-TDHF or NEO-TDDFT working
      equation to have an imaginary eigenvalue solution. Electron-proton systems could
      potentially exhibit three types of instabilities: electronic, protonic, and
      electron-proton vibronic instabilities. The internal and external stabilities for
      theories with different constraints on the spin and spatial orbitals can be
      analyzed. This stability analysis is a useful tool for characterizing SCF
      solutions and is helpful when searching for lower-energy solutions. Initial
      applications to HCN, HNC, and 2-cyanomalonaldehyde, in conjunction with NEO ?SCF
      calculations, highlight possible connections between stationary points in nuclear
      coordinate space for conventional electronic structure calculations and
      stationary points in orbital space for NEO calculations.

PMID- 30193502
TI  - Off-center charge model revisited: Electrical double layer with multivalent
      cations.
AB  - The off-center charge model of ions is a relatively simple model for introducing
      asymmetry in Coulomb interaction while retaining the simplicity and convenience
      of the spherical hard core geometry. A Monte Carlo simulation analysis of the
      planar electric double layer formed by this ionic model for 1+:1- valence systems
      [S. Lamperski et al., Langmuir 33, 11554-11560 (2017)] is extended to include
      solutions of multivalent (2+, 3+) hard spherical cations and single valence (1-)
      hard spherical anions near a uniformly charged, planar electrode. The solvent is
      modelled as a uniform dielectric continuum with a dielectric constant equal to
      that of the pure solvent, viz., the primitive model. Results are reported for the
      ion density, the cation charge profile, and the electrostatic potential profile
      at 1 mol/dm3 salt concentration. Additionally, the double layer potential drop,
      that is, the electrode potential, and the integral and the differential
      capacitances are computed as functions of the electrode surface charge density.
      The latter two quantities show an expected asymmetry as long as the cation
      valence is not too great and the charge of the off-center ion cannot approach too
      close to the electrode surface. It is unusual that the integral and differential
      capacitances are negative for high valence cations and a negatively charged
      electrode when the off-center charge is large and can be very near the surface of
      the electrode. The corresponding electrode potential versus surface charge
      density curve becomes non-monotonic and shows a change of slope, and thus the
      resultant integral and differential capacitances can become negative. This
      nonphysical result is the result of an incipient singularity when a large
      positive charge is too near a negatively charged electrode. Overall, the off
      center charge model suggests a useful recipe to model electrical asymmetry within
      the broader context of the primitive model provided that the off-center charge is
      not too near the surface of the electrode.

PMID- 30193503
TI  - Conformational preferences of Criegee intermediates: Isopropyl substituted
      carbonyl oxide.
AB  - Three conformers of the isopropyl-substituted Criegee intermediate, (CH3)2CHCHOO,
      have been observed by Fourier transform microwave spectroscopy. The transient
      species was produced using a pulsed electric discharge of a gas mixture of 1,1
      diiodo-2-methylpropane/O2 diluted in Ar or Ne. The use of different carrier gases
      in the supersonic expansion reveals the difference of the collisional relaxation
      process between anti-conformers. The conformational relaxation pathways have been
      investigated theoretically and are presented as well. In light of these results,
      the previous study on the ethyl-substituted Criegee intermediate, where the
      absence of one of the four possible conformers was associated with collisional
      relaxation processes, has been re-examined. Here we report the detection of a new
      conformer of the ethyl-substituted Criegee intermediate observed using Ne as the
      seeding gas.

PMID- 30193504
TI  - Monitoring the effect of asymmetrical vertical strain on Janus single layers of
      MoSSe via vibrational spectrum.
AB  - Using first principles calculations, we study the structural and phononic
      properties of the recently synthesized Janus type single layers of molybdenum
      dichalcogenides. The Janus MoSSe single layer possesses 2H crystal structure with
      two different chalcogenide sides that lead to out-of-plane anisotropy. By virtue
      of the asymmetric structure of the ultra-thin Janus type crystal, we induced the
      out-of-plane anisotropy to show the distinctive vertical pressure effect on the
      vibrational properties of the Janus material. It is proposed that for the
      corresponding Raman active optical mode of the Janus structure, the phase
      modulation and the magnitude ratio of the strained atom and its first neighbor
      atom adjust the distinctive change in the eigen-frequencies and Raman activity.
      Moreover, a strong variation in the Raman activity of the Janus structure is
      obtained under bivertical and univertical strains. Not only eigen-frequency
      shifts but also Raman activities of the optical modes of the Janus structure
      exhibit distinguishable features. This study reveals that the vertical
      anisotropic feature of the Janus structure under Raman measurement allows us to
      distinguish which side of the Janus crystal interacts with the externals
      (substrate, functional adlayers, or dopants).

PMID- 30193505
TI  - An efficient hybrid orbital representation for quantum Monte Carlo calculations.
AB  - The scale and complexity of the quantum system to which real-space quantum Monte
      Carlo (QMC) can be applied in part depends on the representation and memory usage
      of the trial wavefunction. B-splines, the computationally most efficient basis
      set, can have memory requirements exceeding the capacity of a single
      computational node. This situation has traditionally forced a difficult choice of
      either using slow internode communication or a potentially less accurate but
      smaller basis set such as Gaussians. Here, we introduce a hybrid representation
      of the single particle orbitals that combine a localized atomic basis set around
      atomic cores and B-splines in the interstitial regions to reduce the memory usage
      while retaining the high speed of evaluation and either retaining or increasing
      overall accuracy. We present a benchmark calculation for NiO demonstrating a
      superior accuracy while using only one eighth of the memory required for
      conventional B-splines. The hybrid orbital representation therefore expands the
      overall range of systems that can be practically studied with QMC.

PMID- 30193506
TI  - Low-energy methane scattering from Pt(111).
AB  - We have measured the temperature dependence of angular distributions of CH4 from
      Pt(111) at an incident energy of 109 meV. A broad angular distribution has been
      observed along the two main symmetry directions, whereby the peak center shifts
      from the supra-specular position to the sub-specular position when the surface
      temperature increases from 120 K to 800 K. Different widths have been measured
      for the scattering patterns along the [ 1-01 ] and the [ 2-11 ] azimuthal
      directions. Based on calculations performed within the binary collision model,
      these differences have been ascribed to different corrugations of the CH4-Pt(111)
      interaction potential along the two high-symmetry directions. This corrugation
      has been estimated from the model calculations to amount ~0.03 A, a factor of
      three larger than the one measured with helium diffraction.

PMID- 30193507
TI  - Percolation in supercritical water: Do the Widom and percolation lines coincide?
AB  - Hydrogen bonding distinguishes water from simpler fluids. Here, we use classical
      molecular dynamics to study the percolation transition in the hydrogen bond
      network of supercritical water. We find that, contrary to some previous work, the
      percolation line in both the pressure-temperature and density-temperature planes
      does not coincide with the Widom line. This difference stems from a fundamental
      distinction between the Widom line, which is thermodynamic in nature, and the
      percolation transition, which depends only on connectivity. For example, we show
      that percolation-related quantities collapse onto master curves when plotted with
      respect to a measure of connectivity rather than thermodynamic variables. We then
      use the Galam-Mauger formula to understand the properties of the hydrogen bonding
      network. We find that the percolation transition in supercritical water can shed
      light on the hydrogen bonding network in room temperature liquid water.

PMID- 30193508
TI  - Fluctuating hydrodynamics of reactive liquid mixtures.
AB  - Fluctuating hydrodynamics (FHD) provides a framework for modeling microscopic
      fluctuations in a manner consistent with statistical mechanics and nonequilibrium
      thermodynamics. This paper presents an FHD formulation for isothermal reactive
      incompressible liquid mixtures with stochastic chemistry. Fluctuating
      multispecies mass diffusion is formulated using a Maxwell-Stefan description
      without assuming a dilute solution, and momentum dynamics is described by a
      stochastic Navier-Stokes equation for the fluid velocity. We consider a
      thermodynamically consistent generalization for the law of mass action for non
      dilute mixtures and use it in the chemical master equation (CME) to model
      reactions as a Poisson process. The FHD approach provides remarkable
      computational efficiency over traditional reaction-diffusion master equation
      methods when the number of reactive molecules is large, while also retaining
      accuracy even when there are as few as ten reactive molecules per hydrodynamic
      cell. We present a numerical algorithm to solve the coupled FHD and CME equations
      and validate it on both equilibrium and nonequilibrium problems. We simulate a
      diffusively driven gravitational instability in the presence of an acid-base
      neutralization reaction, starting from a perfectly flat interface. We demonstrate
      that the coupling between velocity and concentration fluctuations dominates the
      initial growth of the instability.

PMID- 30193509
TI  - Demonstration of multi-hit and multi-mass capability of 3D imaging in a
      conventional velocity map imaging experiment.
AB  - Coincidence and three-dimensional (3D) imaging offer unique capability in
      photodissociation and scattering experiments, and a variety of methods have been
      developed. The basic concept behind all these approaches is to register both the
      position (x, y) at which the particle hits the detector and the arrival time (t).
      A novel advance to the time and position sensitive detection was introduced
      recently by Li and co-workers [Rev. Sci. Instrum. 85(12), 123303 (2014)]. This
      method utilizes a high-speed digitizer and a computer algorithm along with the
      camera and detector usually employed in a conventional velocity map imaging
      apparatus. Due to the normal intensity variations of the ion spots, a correlation
      can be made between ion intensity recorded by the camera and peak intensity in
      the digitizer. This makes it possible to associate each ion spot's position with
      its respective arrival time, thereby constructing a 3D distribution. The
      technique was primarily introduced for ultrafast ion and electron imaging
      experiments at high repetition rate with single or few events per image frame. We
      have recently succeeded in adapting this approach at low repetition rate.
      Modifications were done to the initial setup to enhance the acquisition
      efficiency to obtain and correlate multiple hits per laser shot rather than
      single-hit events. The results are demonstrated in two experiments, dimethyl
      amine dissociative ionization at 205 nm and carbonyl sulfide photodissociation at
      217 nm, with up to 27 events correlated in a single frame. Temporal and spatial
      slicing capabilities were achieved with good resolution, giving the photofragment
      velocity and angular distribution for multiple masses simultaneously.

PMID- 30193510
TI  - Integrated tempering enhanced sampling method as the infinite switching limit of
      simulated tempering.
AB  - A fast and accurate sampling method is in high demand, in order to bridge the
      large gaps between molecular dynamic simulations and experimental observations.
      Recently, an integrated tempering enhanced sampling (ITS) method has been
      proposed and successfully applied to various biophysical examples, significantly
      accelerating conformational sampling. The mathematical validation for its
      effectiveness has not been elucidated yet. Here we show that the integrated
      tempering enhanced sampling method can be viewed as a reformulation of the
      infinite switching limit of the simulated tempering method over a mixed
      potential. Moreover, we demonstrate that the efficiency of simulated tempering
      molecular dynamics improves as the frequency of switching between the
      temperatures is increased, based on the large deviation principle of empirical
      distributions. Our theory provides the theoretical justification of the advantage
      of ITS. Finally, we illustrate the utility of the infinite switching simulated
      tempering method through several numerical examples.

PMID- 30193511
TI  - Dynamics of electron attachment and photodissociation in iodide-uracil-water
      clusters via time-resolved photoelectron imaging.
AB  - The dynamics of low energy electron attachment to monohydrated uracil are
      investigated using time-resolved photoelectron imaging to excite and probe iodide
      uracil-water (I-.U.H2O) clusters. Upon photoexcitation of I-.U.H2O at 4.38 eV,
      near the measured cluster vertical detachment energy of 4.40 eV +/- 0.05 eV,
      formation of both the dipole bound (DB) anion and valence bound (VB) anion of I
      .U.H2O is observed and characterized using a probe photon energy of 1.58 eV. The
      measured binding energies for both anions are larger than those of the non
      hydrated iodide-uracil (I-.U) counterparts, indicating that the presence of water
      stabilizes the transient negative ions. The VB anion exhibits a somewhat delayed
      400 fs rise when compared to I-.U, suggesting that partial conversion of the DB
      anion to form the VB anion at early times is promoted by the water molecule. At a
      higher probe photon energy, 3.14 eV, I- re-formation is measured to be the major
      photodissociation channel. This product exhibits a bi-exponential rise; it is
      likely that the fast component arises from DB anion decay by internal conversion
      to the anion ground state followed by dissociation to I-, and the slow component
      arises from internal conversion of the VB anion.

PMID- 30193512
TI  - Single-root networks for describing the potential energy surface of Lennard-Jones
      clusters.
AB  - Potential energy surface (PES) holds the key in understanding a number of atomic
      clusters or molecular phenomena. However, due to the high dimension and
      incredible complexity of PES, only indirect methods can be used to characterize a
      PES of a given system in general. In this paper, a branched dynamic lattice
      searching method was developed to travel the PES, which was described in detail
      by a single-root network (SRN). The advantage of SRN is that it reflects the
      topological relation between different conformations and highlights the size of
      each structure energy trap. On the basis of SRN, to demonstrate how to transform
      one conformation to another, the transition path that connects two local minima
      in the PES was constructed. Herein, we take Lennard-Jones (LJ) clusters at the
      sizes of 38, 55, and 75 as examples. It is found that the PES of these three
      clusters have many local funnels and each local funnel represents one morphology.
      If a morphology is located more frequently, it will lie in a larger local funnel.
      Besides, certain steps of the transition path were generated successfully, such
      as changing from icosahedral to truncated octahedral of the LJ38-cluster. Though
      we do not exhibit all the parts of the PES or all transition paths, this method
      indeed works well in the local area and can be used more widely.

PMID- 30193513
TI  - Thermodynamics of the hard-disk fluid at a planar hard wall: Generalized scaled
      particle theory and Monte Carlo simulation.
AB  - A generalized scaled-particle theory for the uniform hard-disk mixture is derived
      in the spirit of the White Bear II free energy of the hard-sphere fluid [H.
      Hansen-Goos and R. Roth, J. Phys. C: Condens. Matter 18, 8413 (2006)]. The theory
      provides a very simple result for the interfacial free energy gamma of the hard
      disk fluid at a planar hard wall (which in d = 2 is a line) in terms of the
      equation of state. To complement and assess the theory, we perform Monte Carlo
      simulations from which we obtain gamma using Gibbs-Cahn integration. While we
      find excellent overall agreement between theory and simulation, it also becomes
      apparent that the set of scaled-particle variables available in d = 2 is too
      limited, prohibiting a quasi-exact result for gamma. Furthermore, this is
      reflected in the mixture equation of state resulting from our theory, which,
      similar to a previous attempt by Santos et al. [Mol. Phys. 96, 1 (1999)],
      displays a small but systematic deviation from simulations.

PMID- 30193514
TI  - Non-equilibrium solvation dynamics in water-DMSO binary mixture: Composition
      dependence of non-linear relaxation.
AB  - Because of a larger number of intermolecular interactions and configurations
      available to them, aqueous binary mixtures exhibit a variety of dynamics that are
      not seen in pure liquids, often hard to understand or predict, and have attracted
      considerable interest recently. Among all such solutions, mixtures of water and
      dimethyl sulfoxide (DMSO) stand out for their unique role in chemistry and
      biology. The low DMSO concentration regime of the water-dimethyl sulfoxide (DMSO)
      mixture is relevant in wide ranging chemical and biological processes.
      Interestingly, this low concentration regime is known to display a string of yet
      unexplained anomalies. We probe these anomalies in atomistic simulations by
      studying (i) equilibrium solvation dynamics both in the ground and the excited
      states of the probe separately and (ii) the non-equilibrium solvation dynamics
      subsequent to excitation at time t = 0 and then following the solvation process.
      The latter needed a large number of simulations to obtain a reliable average. We
      carried out such studies across a large number of compositions of the water-DMSO
      mixture. We find that the usually employed linear response approximation breaks
      down at those concentrations where binary mixtures display other anomalies. The
      non-linearity is reflected in substantially different solvent responses in the
      ground and in the excited states of the solute probe indole and also in non
      equilibrium solvation. The difference is maximum near 20%-35% of the DMSO
      concentration regime.

PMID- 30193515
TI  - Differential diagnosis of anemia.
AB  - Anemia, defined as hemoglobin level under lower normal limit, is a symptom of
      different pathologic conditions and the accurate differential diagnosis is
      necessary to determine the cause of anemia. The article uses the morphological
      classification of anemia to distinguish macrocytic, normocytic and microcytic
      types of anemias and divides anemias with increased amount of peripheral blood
      reticulocytes as a special group. It describes commonly known clinical units as
      iron deficiency anemia or anemia of chronic disease, as so as rare clinical
      units, which are always need to think about in a differential diagnosis of an
      anemic patient. There is an increasing incidence of rare blood disorders due to
      introduction of molecular genetics methods into diagnostics, prolonged overall
      survival of patients and increasing migration from areas with endemic occurrence
      of these diseases. Etiology, basic pathophysiological mechanisms, main clinical
      features together with important diagnostic examinations are described by each
      clinical unit. Due to the differential diagnostic focus of the article only basic
      knowledge about therapy is mentioned. The authors are members of the IHBT Center
      for Rare Disorders of Hematopoiesis, which is focused mainly on congenital and
      acquired disorders of red blood cell. Key words: anemia - differential diagnosis 
      enzymopathies - hemoglobinopathies - iron - macrocytosis - microcytosis - rare
      blood disorders - reticulocytosis.

PMID- 30193516
TI  - Hemoglobinopathies.
AB  - This article summarize molecular-genetic basis of hemoglobinopathies, their
      classification and phenotypic manifestations. The description of individual
      subgroups is supplemented with a case reports of patients diagnosed in the Czech
      population. This paper provides an overview of 14 types of alpha-thalassemic
      mutations, 34 beta-thalassemic alleles, 4 deltabeta-thalassemic alleles and 22
      hemoglobin variants identified in the Czech population in 876 persons from 579
      families. In more detail are described hemoglobinopathies, that have been
      diagnosed and described as novel: beta-thalassemic mutation CD 38/39 (-C); Hb
      Olomouc; Hb Hana; Hb Hradec Kralove and 18.3 kb deletion downstream of alpha
      globin cluster leading to a new mechanism of alpha-thalassemia-2. The fact that
      until the end of 2017 hemoglobinopathies were diagnosed in nearly 900 patients
      shows that they are not rare in the Czech Republic. This brings increased demands
      for their diagnostics, including prenatal diagnosis. Key words:
      hemoglobinopathies - hemoglobinopathy with high affinity to oxygen - sickle cell
      anemia - thalassemia - thalassemic hemoglobinopathy - unstable hemoglobins.

PMID- 30193517
TI  - Rare anemias from the group of congenital bone marrow failure syndromes.
AB  - This review summarizes the pathophysiology, genetic background and clinical
      symptoms of anemias belonging to the group of inherited bone marrow failure
      syndromes with unilineage failure of erythropoiesis. It sums up the current
      knowledge of three diseases: Diamond-Blackfan anemia, congenital
      dyserythropoietic anemia and Fanconi anemia whose pathophysiology was elucidated
      in detail during the last decade, owing to the rapid development of new molecular
      genetic techniques, especially next-generation sequencing. Fanconi anemia is
      included in this overview because of macrocytosis and/or anemia detected in the
      majority of the patients before they develop bone marrow failure. The paper also
      aims at pointing out typical associated anomalies in these diseases which might
      be overlooked and which can lead to early diagnosis. Unfortunately, the correct
      diagnosis is often established later in adulthood and, in some cases, as late as
      at the time of manifestation of malignant disease. Accurate and timely diagnosis
      of these conditions is extremely important for the determination of appropriate
      treatment approach, diagnosis of affected family members (especially in the
      process of bone marrow donor search), and genetic counselling, which can
      substantially influence the prognosis of these diseases. Key words: congenital
      dyserythropoietic anemia - Diamond-Blackfan anemia - DNA repair -
      dyserythropoiesis - Fanconi anemia - inherited bone marrow failure -
      ribosomopathies.

PMID- 30193518
TI  - Aplastic anemia.
AB  - Aplastic anemia - bone marrow failure (AA) is defined as pancytopenia with
      hypocellular bone marrow without signs of marrow fibrosis or of presence of
      abnormal cells. Recent studies showed that most of AA cases might be mediated by
      immune mechanisms. Toxic agent leads to expression of neoantigens or cryptic
      antigens on the surface of pluripotent hematopoietic stem cells with subsequent
      activation of immune effector cells and induction of stem cell apoptosis.
      Histopathological findings obtained from bone marrow biopsy are crucial for
      diagnosis of AA. Hypoplastic MDS, PNH, hairy cell leukemia and late manifestation
      of congenital cytopenias must be excluded in differential diagnosis. Allogeneic
      stem cell transplantation from HLA matched related donor or combined immune
      suppression represent the first line treatment for patients with severe AA (SAA).
      Transplantation from unrelated donor may be a second line treatment for patients
      who failed to respond to immunosuppressive therapy. Recent studies showed
      eltrombopag or its combination with immune supression as an effective therapeutic
      approach to AA patients. Up to 15 % of AA patients may later develop PNH, MDS or
      acute leukemia. An influence of disturbed immune mechanisms as well as of
      immunosuppressive treatment on the development of clonal proliferation is
      currently discussed.  Key words: aplastic anemia - diagnosis - eltrombopag -
      immunosuppression - transplantation - treatment.

PMID- 30193519
TI  - Paroxysmal nocturnal hemoglobinuria.
AB  - Paroxysmal nocturnal hemoglobinuria (PNH) results from a deficiency in inhibitors
      of activated complement. This lack leads to complement mediated intravascular
      hemolysis, to activation of coagulation system with increased risk of thrombotic
      complications and to various degree of bone marrow failure. A molecular basis of
      PNH is a somatic mutation of PIGA gene causing a lack of glycosyl phosphatidyl
      inositol which binds many important antigens to cell surface membrane including
      inhibitors of activated complement CD59 and CD55 antigens. Presence of CD59 and
      CD55 deficient cells in peripheral blood detected by flow cytometry is essential
      for diagnosis of PNH. Standard treatment of PNH includes transfusions of
      leukocyte depleted red blood cells, anticoagulation prophylaxis and
      administration of folinic acid. PNH patients with predominant signs of bone
      marrow failure and profound cytopenia may by candidates for stem cell
      transplantation or combination immunosuppression. Patients with severe hemo-lysis
      and/or thrombotic complications are indicated for administration of eculizumab -
      a monoclonal antibody against C5 part of complement. Key words: diagnosis -
      eculizumab - immunosuppression - paroxysmal nocturnal hemoglobinuria -
      pathogenesis - transplantation - treatment.

PMID- 30193520
TI  - Autoimmune hemolytic anemia.
AB  - Autoimmune hemolytic anemia (AIHA) is caused by auto-antibodies directed against
      self red blood cell (RBC) surface antigens. A consequence may be an intravascular
      hemolysis mediated by activated complement or extravascular hemolysis caused by
      destruction of complex of RBC with autoantibody in spleen and liver. The basic
      classification subdivides AIHA in primary/idiopathic and secondary with known
      underlying disease. A classification according to the thermal range of antibody
      recognizes warm AIHA, cold aglutinin disease (CAD), mixed AIHA and paroxysmal
      cold hemoglobinuria. Pathogenesis of AIHA consists of a defective antigen
      presentation to immunocompetent cells, insufficient process of T-lymphocyte
      tolerance to autoantigens and induction of autoantibody production by B
      lymphocytes. For the diagnosis of AIHA are essential direct and indirect
      antiglobulin tests. The first-line therapy for warm AIHA is still administration
      of corticosteroids. For non-responding patients, second-line treatment includes
      rituximab or splenectomy. Combination of other immunosuppressive drugs represents
      a third-line treatment for resistant/relapsing patients. Rituximab is a treatment
      of choice for patients with CAD. Key words: anemia hemolytic - autoimmunity -
      corticosteroids - diagnosis - pathogenesis - rituximab - splenectomy - treatment.

PMID- 30193521
TI  - Granulocytopenia.
AB  - Granulocytopenia is defined as a decrease of peripheral blood granulocytes below
      lower limit of normal range. Patients with severe granulocytopenia -
      agranulocytosis exhibit < 0.5 * 109/l granulocytes in peipheral blood.
      Granulocytopenia may result from congenital or acquired defective production of
      granulocyte precursors or it may be a consequence of increased destruction of
      mature granulocytes, most frequently caused by immune mechanisms. Investigation
      of origin of granulocytopenia must be connected with exclusion of etiological
      agents causing secondary neutropenia (infections, autoimmune disorders, drugs,
      LGL syndrome). Patients with > 0.5 * 109/l of granulocytes usually do not exhibit
      clinical symptoms unless they do not suffer from a concomitant disease
      (especially immunodeficiency). Patients with severe granulocytopenia are
      indicated for supportive treatment and for administration of G-CSF. Children with
      severe congenital neutropenia (SCN) are at risk of later development of MDS or
      AML and are candidates for SCT when signs of disease progression appears. Key
      words: diagnosis - granulocytopenia - growth factors - pathogenesis -
      transplantation -treatment.

PMID- 30193522
TI  - Diagnosis and treatment of immune thrombocytopenia.
AB  - The diagnosis of immune thrombocytopenia consists in the combination of
      laboratory and clinical pictures of thrombocytopenia while eliminating other
      disorders characterized by low levels of thrombocytes. The treatment initiation
      in patients with ITP is recommended when the thrombocyte count has dropped below
      20-30 * 109/l, when hemorrhagic manifestations occur and depending on the
      patient's risk profile. Corticoids and IVIG are used as first-line treatment.
      Second-line treatment includes splenectomy, immunosuppressive therapy and
      administration of thrombopoietin receptor agonists. A new drug in the treatment
      of ITP is fostamatinib. Key words: corticoids - eltrombopag - fostamatinib -
      immune thrombocytopenia - IVIG -  rituximab - romiplostim - sustainable remission
      - splenectomy.

PMID- 30193524
TI  - Diagnostic strategies in disorders of hemostasis.
AB  - Hemostasis is a complicated biological system, where the balance between
      procoagulation and anticoagulation processes maintains fluidity of blood through
      intact blood vessels and creates thrombi when it is needed to prevent bleeding
      from the impaired vessels. The modern model of hemostasis is divided into 2
      principal phases, the first being defined as primary hemostasis which involves
      the platelet-vessel interplay, while the second, defined as secondary hemostasis,
      mainly involves coagulation factors and surfaces of activated cells. The
      activation and amplification of the coagulation cascade is regulated by natural
      inhibitors of coagulation. The blood clots which arise to prevent loss of blood
      must subsequently be broken down and the compact blood vessel wall must be
      restored. This process is called fibrinolysis. Bleeding and thromboses are
      manifestations of the impaired hemostatic balance. Detection of its cause is
      important for efficient treatment and prevention of the condition. This requires
      a combined evaluation of the family and personal history, a clinical anamnesis
      along with the evaluation of laboratory results. It is not reasonable or
      economical to perform all the available tests of hemostasis at the same time. It
      is recommendable to proceed from the global to the screening and then special
      tests and, through the process of elimination, obtain an explanation of the
      bleeding or prothrombotic phenotypes. The purpose of this report is to provide a
      brief overview of the principal causes of the hemostatic disorders and the
      practices which facilitate their diagnosis. Key words: diagnosis of hemorrhagic
      manifestations - diagnostics of thrombophilias - DIC diagnostics - hemophilia A -
      thrombopathy - von Willebrand disease.

PMID- 30193523
TI  - Hematopoietic stem cell transplantation for non-malignant hematological
      disorders.
AB  - Allogeneic hematopoietic stem cell transplantation (HSCT) is currently
      successfully used in the treatment of many non-malignant hematopoietic disorders,
      including acquired and inherited bone marrow failure. HSCT from a HLA-identical
      sibling donor (MSD) is the treatment of choice, better results are achieved using
      bone marrow graft. Conditioning regimens and graft-versus-host disease
      prophylaxis are different in dependence on the underlying disease, age and
      clinical condition of the patient, type of donor and stem cell graft.
      Transplantation from MSD is the first-line treatment for children and young
      adults with SAA. Patients with hemoglobinopathies and inherited bone marrow
      failure syndromes with available MSD should be referred for transplantation as
      soon as possible, before the development of serious complications and iron
      overload-related tissue damage. Indications for HSCT from matched unrelated donor
      in the treatment of non-malignant hematopoietic disorders are expanding in
      dependence on very good results in the last two decades. The aim of successfully
      HSCT is not only to increase the percentage of surviving patients but also to
      improve the quality of life with the minimum of early complications and late
      effects. Key words: allogeneic hematopoietic stem cell transplantation - aplastic
      anemia - hemoglobinopathy - inherited bone marrow failure.

PMID- 30193525
TI  - Congenital and acquired bleeding disorders.
AB  - Hemostasis can be characterized as an array of physiological mechanisms providing
      both blood fluidity in the intact blood vessels and hemostasis in the event of
      impaired continuity of the blood vessel wall. The impaired hemo-static balance
      may lead on the one hand to an increased tendency to bleed, either spontaneously
      or only in response to an external stimulus. At the opposite end of bleeding are
      thrombophilic conditions characterized by an increased tendency to blood
      coagulation and thereby to the development of venous or arterial thrombosis. The
      hemostatic balance is the result of normal functioning of the blood vessel wall,
      platelets and plasma agents which include the coagulation and fibrinolytic
      systems and their inhibitors. By coagulation we understand the process leading to
      the formation of fibrin networks including the controlled interaction of
      coagulation factors. It is a physiological process as opposed to thrombosis which
      can be defined as increased coagulation under pathological conditions. Key words:
      coagulation - coagulation factors - coagulopathy - hemophilia - inhibitors of
      coagulation factors deficiencies - purpura - thrombocytopathy - thrombocytopenia.

PMID- 30193526
TI  - Investigation of congenital thrombophilic conditions: when, in whom, focusing on
      what or not at all?
AB  - Venous thromboembolism is a multifactorial disease. Inherited thrombophilia is
      linked with increased risk of VTE and we know about them more than 50 years.
      Through a robust thrombophilia work-up in the end of millenium, the criteria for
      testing have significantly gone down. It is associated with increased amount of
      information about clinical consequence of testing. We discuss current
      recommendations not only in the literature, but also in our clinic. Key words:
      criteria for testing - thrombophilia - venous thromboembolism.

PMID- 30193527
TI  - Antithrombotics today.
AB  - Over the last 10 years some new drugs affecting blood clotting - antithrombotics 
      were invented. For more than half a century only warfarin and heparin were
      available. A better understanding of the pathways involved in activation of blood
      clotting, the links between these systems, and the impact of thrombosis on
      inflammation, have led to identification of new targets and development of new
      drugs, especially new antiplatelet drugs and anticoagulants. With the advent of
      new drugs into clinical practice, treatment options of thrombotic complications
      are expanding. However, it is always necessary to get familiar with the drug and
      its properties and to know its limitations. This is the only way to offer
      patients the best practices. Key words: anticoagulant - antithrombotic - Direct
      Oral AntiCoagulant (DOAC) - laboratory monitoring - Low-Molecu-lar-Weight
      Heparins (LMWH) - New Oral Anticoagulants/Non-vitamin K Oral AntiCoagulants
      (NOAC) - unfractionated heparin (UFH) - warfarin.

PMID- 30193528
TI  - Development and Validation of the Positive Parenting Schema Inventory (PPSI) to
      Complement the Young Parenting Inventory (YPI) for Schema Therapy (ST).
AB  - The factor structure of an initial item pool of 207 positive parenting items was
      investigated (Manila; n = 520, 538) to develop the Positive Parenting Schema
      Inventory. Single group and multigroup confirmatory factor analyses of the
      Positive Parenting Schema Inventory showed invariance of the factor structure in
      six out of the seven levels on two other independent samples (Eastern, Indonesia;
      n = 366, 383; Western, the United States; n = 204, 214). Good values for
      reliability were obtained for its seven subscales (50 items) using coefficient
      omegas (.71 to .95). Evidence of validity based on test content, response
      processes (item responses to desired inferences), internal structure (exploratory
      and confirmatory factor analyses), relations to other variables (correlations
      with other instruments), and consequences of testing (correlations with positive
      schemas) were demonstrated. A core tenet of schema therapy theory was supported
      in that recall of past positive parenting patterns were associated with current
      levels of positive schemas.

PMID- 30193529
TI  - Ectopic anteriorly rotated left kidney causing diaphragmatic eventration.

PMID- 30193530
TI  - Chasing the umbrella: delayed migration of ductal occluder device into the aorta.
AB  - Delayed migration of a ductal occluder device into the aorta after transcatheter
      closure of a patent ductus arteriosus is extremely rare. We present a case of
      delayed migration of a ductal occluder into the descending aorta 4 months after
      its deployment in an 11-year-old girl. Successful surgical removal of the device
      from the descending aorta and triple-ligation of the ductus arteriosus was
      performed via a left thoracotomy. The patient made an uneventful recovery.

PMID- 30193531
TI  - One more method for arterial cannulation in aortic arch surgery ("Penza
      cannulation").
AB  - Here we propose a new method of aortic cannulation in type A aortic dissection
      and aortic arch aneurysms. Aortic cannulation is performed through any of the
      ostia of brachiocephalic arteries and has been successfully used in 77 patients.
      This procedure is simple, safe, effective, and might be used as one of the
      alternatives to the classic methods of arterial cannulation.

PMID- 30193532
TI  - Recent developments in the use of biologics targeting IL-5, IL-4, or IL-13 in
      severe refractory asthma.
AB  - INTRODUCTION: Severe or refractory asthma is seen in approximately 5% of
      asthmatic subjects who have unsatisfactory symptom control despite adherence to
      high-dose inhaled glucocorticoid therapies resulting in significant morbidity,
      reduced quality of life and health-care cost implications. Asthma exhibits marked
      heterogeneity both clinically and at the molecular phenotypic level requiring
      specifically targeted treatments to block the key pathways of the disease.
      Monoclonal antibody-based biologics targeted at inhibition of the type 2
      cytokines IL-4, IL-5, and IL-13 have considerable potential as effective
      treatments for severe asthma. Areas covered: This review is based on recent
      English-language original articles in PubMed or Medline that reported significant
      clinical findings on the current status, therapeutic potential, and safety of
      biologics targeted at IL-4, IL-5, and IL-13 in the treatment of asthma together
      with the potential utility of simple reproducible non-invasive biomarkers to
      guide the effective use of biologic-based therapy that do not require direct
      sampling of the airways Expert commentary: The further development of
      reproducible and straightforward discriminatory non-invasive biomarkers may aid
      identification of those patients most likely to benefit from treatment with these
      interventions.

PMID- 30193533
TI  - Right ventricular involvement in transthyretin amyloidosis.
AB  - BACKGROUND: The extent of right ventricular (RV) involvement in transthyretin
      amyloidosis (ATTR) is unknown. OBJECTIVES: This study sought to establish the
      degree of RV involvement in ATTR amyloidosis, and compare findings with RV
      involvement in hypertrophic cardiomyopathy (HCM). METHODS: Forty-two patients
      with ATTR amyloidosis and echocardiographic evidence of cardiac amyloidosis
      (cardiac ATTR), 19 ATTR patients with normal left ventricular (LV) wall thickness
      (non-cardiac ATTR), 25 patients with diagnosed HCM and 30 healthy controls were
      included in this study. Echocardiographic measurements for conventional
      parameters, as well as RV global and segmental strain, were recorded. RESULTS:
      When comparing RV structure and function between cardiac ATTR amyloidosis and HCM
      patients, only segmental strain differed between the two groups. In cardiac ATTR
      amyloidosis, we found an RV apex-to-base strain gradient with highest deformation
      in the apex. This pattern was reversed in patients with HCM. CONCLUSIONS: RV
      involvement is common in cardiac ATTR patients. The present study also detected
      an RV apical sparing pattern in patients with ATTR cardiomyopathy, similar to
      what has previously been described for the left ventricle in these patients. This
      pattern was not seen in HCM patients. Further studies are needed to assess the
      clinical importance of these findings.

PMID- 30193534
TI  - Antimicrobial activity of essential oils against foodborne multidrug-resistant
      enterococci and aeromonads in planktonic and biofilm state.
AB  - The selection and use of natural compounds with antimicrobial activity against
      foodborne pathogens is of major importance. The present study evaluated the
      antimicrobial activity of commercial essential oils against multidrug-resistant
      Enterococcus spp. and Aeromonas spp. Cymbopogon flexuosus and Thymus vulgaris
      essential oils presented the highest inhibitory zones against both bacterial
      groups ( p < 0.05). Subsequent determination of the minimum inhibitory
      concentrations showed values between 0.47 and 1.9 mg/ml for Aeromonas spp. and
      from 1.9 to 15 mg/ml for Enterococcus spp. The antimicrobial effect of C.
      flexuosus and T. vulgaris essential oils was also assessed against biofilms.
      Bacteria in biofilm state were subjected to 30 min or 1 h of exposure to each
      essential oil and eradication ability estimated by colony counting. Both
      essential oils exhibited antimicrobial activity against preformed Aeromonas
      biofilms, but were unable to successfully eradicate biofilms produced by
      enterococci, in the conditions under investigation. Nonetheless, the presumptive
      use of essential oils in the food industry should be considered in further
      investigations.

PMID- 30193535
TI  - 'There is still so much inside': The impact of personalised reminiscence,
      facilitated by a tablet device, on people living with mild to moderate dementia
      and their family carers.
AB  - The aim of this qualitative study was to explore the impact of a home-based,
      personalised reminiscence programme facilitated through an iPad app on people
      living with dementia and their family carers. Semi-structured interviews were
      used to collect data from 15 people living with dementia and 17 family carers
      from a region of the United Kingdom. The interviews were recorded, transcribed
      and analysed using thematic analysis. Six key themes emerged related to usability
      ('It's part of my life now'); revisiting the past ('Memories that are important
      to me'); home use ('It was homely'); impact on the person living with dementia
      ('It helped me find myself again'); gains and abilities ('There is still so much
      inside') and impact on relationships ('It's become very close'). These themes
      highlighted the impact of the reminiscence experience at an individual and
      relationship level for people living with dementia and their carers. The
      reminiscence experience also appeared to facilitate the development of new
      insights among participants that emphasised abilities and gains rather than
      disabilities and losses. The significance of personal memories was a core theme
      although this was not without its challenges, particularly if memories were
      distressing. The reminiscence experience was differentiated by individual roles.
      Carers tended to become more relationship-focused, whereas people living with
      dementia highlighted the significance of learning new skills. The study concluded
      that individual specific reminiscence supported by an iPad app can have a
      positive impact on people living with dementia and their carers at an individual
      and relationship level.

PMID- 30193536
TI  - A mixed methods systematic review of multimodal non-pharmacological interventions
      to improve cognition for people with dementia.
AB  - Objective Multimodal non-pharmacological interventions have been argued to have
      the potential to complement current pharmacological approaches to improving
      quality of life for people living with dementia. The aim of this review was to
      identify, synthesise and appraise the evidence for the effectiveness of
      multimodal non-pharmacological interventions for improving cognitive function
      specifically. Method After a comprehensive search strategy including grey
      literature, 26 studies were reviewed. The inclusion criteria concerned adults
      with a primary diagnosis of dementia. Studies used two or more different modes of
      intervention, and measured a cognitive outcome. Due to differences in the
      conceptualisations of the term 'multimodal', a typology of modes and methods was
      developed to facilitate classification of candidate studies. Results Twenty-one
      group studies and five case studies were found. Group studies used two or three
      modes of intervention and multiple methods to implement them. Interventions
      utilised were cognitive, physical, psychological and psychosocial, nutrition,
      fasting, gut health, sleep hygiene, stress reduction, detoxification, hormonal
      health and oxygen therapy. Five individual case studies were found in two
      separate papers. Each personalised patient treatment utilised in-depth
      assessments and prescribed up to nine different modes. In 19 (90%) of the 21
      group comparisons, participants were reported to have cognitive improvements,
      stability with their dementia or a delay in their decline. The extent of these
      improvements in terms of meaningful clinical change was variable. Conclusion
      Multimodal non-pharmacological interventions have the potential to complement
      singular therapeutic approaches by addressing multiple modifiable risk factors
      currently understood to contribute towards cognitive decline.

PMID- 30193537
TI  - Expression of sex steroid receptors and aromatase in adipose tissue in different
      body regions in men with coronary artery disease with and without ischemic
      systolic heart failure.
AB  - BACKGROUND: The hormonal metabolism of adipose tissue differs across regions of
      fat. This issue has never been verified in male patients with coronary artery
      disease (CAD) with and without systolic heart failure (SHF). METHODS: We examined
      90 male patients with CAD with and without SHF and 42 healthy controls. RESULTS:
      In patients with CAD with and without SHF, androgen receptor (AR) expression in
      adipose tissue of the lower leg was higher than AR expression of the thoracic
      wall and epicardial adipose tissue (EAT) (both p < .0001 for SHF patients and
      both p < .001 for patients without SHF). Expression of aromatase in adipose
      tissue of the lower leg among patients with CAD and SHF was higher than aromatase
      expression of the thoracic wall and EAT (p < .001 and p < .05, respectively), and
      in patients without SHF, it was higher only than aromatase expression of the
      thoracic wall (p < .05). There were no differences in expression of estrogen
      receptor (ER) between three regions of adipose tissue both in men with CAD with
      and without SHF. CONCLUSIONS: In male patients with CAD, site-related differences
      of adipose tissue in expression of AR and aromatase are present regardless of
      coexisting SHF with the highest hormonal activity within peripheral subcutaneous
      adipose tissue.

PMID- 30193539
TI  - Peak V'O2 is an independent predictor of survival in patients with cardiac
      amyloidosis.
AB  - INTRODUCTION: Cardiopulmonary exercise testing (CPET) has repeatedly been
      reported to reliably predict adverse outcomes in different forms of heart
      failure. However, it has not been elucidated in detail in cardiac amyloidosis
      (CA). Therefore, we evaluated the predictive value of CPET parameters in patients
      with CA regarding disease severity and prediction of mortality. METHODS: Twenty
      seven consecutive patients with CA were assessed noninvasively, including
      electrocardiography, echocardiography, CPET, and laboratory tests. Clinical data
      were correlated with CPET findings. Univariate and multivariate analyses were
      performed to evaluate predictors of mortality. RESULTS: Within median follow-up
      period of 38 (IQR 43) months 19 (70%) deaths occurred. Patient initially
      presented with signs and symptoms of congestive heart failure NYHA 3 (IQR 1),
      reduced exercise capacity (peak V'O2 15.2 mL/kg body weight) and inefficient
      ventilation in CPET (V'E/V'CO2 slope (30 (IQR 3)), markedly elevated cardiac
      biomarkers (NT-proBNP 1791 (IQR 3249) ng/mL) and echocardiographic signs of
      morphological (septum thickness 18 (IQR 6) mm) and functional cardiac involvement
      (TAPSE 19 (IQR 8) mm). Patients with peak V'O2 below median value presented with
      significantly longer QTc interval when compared to patients with peak V'O2 above
      the median. Further these patients tend to have more pronounced impairment of
      longitudinal function as indicated by lower MAPSE, TAPSE, and elevation of
      cardiac biomarkers. Multivariate analysis revealed peak V'O2 slope as the only
      independent predictor of survival. CONCLUSIONS: We identified reduced peak V'O2
      as an independent predictor of mortality in patients with cardiac involvement in
      different forms of systemic amyloidosis.

PMID- 30193538
TI  - Complete Clinical Remission of Stage IV Triple-Negative Breast Cancer Lung
      Metastasis Administering Low-Dose Immune Checkpoint Blockade in Combination With
      Hyperthermia and Interleukin-2.
AB  - The prognosis of triple-negative breast cancer with metastases after chemotherapy
      remains dismal. We report the case of a 50-year-old female with first disease
      recurrence at the axillary lymph node and, later on, bilateral pulmonary
      metastases with severe shortness of breath. The patient received low-dose immune
      checkpoint blockade (concurrent nivolumab and ipilimumab) weekly over 3 weeks
      with regional hyperthermia 3 times a week, followed by systemic fever-range
      hyperthermia induced by interleukin-2 for 5 days. She went into complete
      remission of her pulmonary metastases with transient WHO I-II diarrhea and skin
      rash. The patient remained alive for 27 months after the start of treatment, with
      recurrence of metastases as a sternal mass, and up to 3 cm pleural metastases.
      This exceptional response should instigate further research efforts with this
      protocol, which consists only of approved drugs and treatments.

PMID- 30193540
TI  - Progressive axonal polyneuropathy in a mitochondrial disorder: an uncommon
      association with familial amyloid neuropathy.

PMID- 30193541
TI  - Enzyme immunoassay may be inadequate for measuring salivary testosterone in older
      men.
AB  - Several correlations have been reported between men's testosterone (T) and other
      characteristics. Stalwart findings are a decline in T during the day, decline
      with obesity, and decline with advancing age. Here seven previously reported
      correlations are tested among older American men in the National Social Life,
      Health and Aging Project (NSHAP), their salivary T measured by enzyme
      immunoassays (EIA). Few significant correlations are found, with most tests
      producing weak or null results. These findings, overall, suggest that T does not
      "work" much among older men. However, a threat to this conclusion is raised by
      Welker et al. namely that EIA of salivary T may contain large errors,
      invalidating the tests. To check this possibility, these correlations from the
      literature were tested among older British men whose salivary T was measured by
      liquid chromatography-tandem mass spectroscopy (LC-MS/MS), a technique noted for
      its specificity. Not all could be tested, but the relationships of T with age,
      obesity, and health are significant among British men, indicating that T remains
      active in older men, and throwing doubt on the adequacy of EIA for measuring
      salivary T.

PMID- 30193542
TI  - Cerebral microbleeds: hearing through the silence-a narrative review.
AB  - OBJECTIVE: The term cerebral microbleed (CMB) refers to lesions documented as
      unexpected findings during computed tomography or magnetic resonance imaging
      examination of the brain. Initially, a CMB was thought to represent hemosiderin
      laden macrophages marking an area of a tiny hemorrhage. Recently, histopathologic
      studies have shown that the structure of a CMB can be variable. To aid in dealing
      with this finding and judging its clinical significance, this review addresses
      important aspects of a CMB, including the definition, prevalence, and incidence
      in various populations, end-organ damage, associated conditions, and whether any
      action or treatment by the clinician might be indicated. METHODS: PubMed Medline,
      EMBASE, BIOSIS, Current Contents, and Derwent Drug Files databases were searched
      for the keywords "microbleeds-detection-damage", "silent bleeds", "microbleeds",
      or "silent bleeds AND hemophilia" from 2011-2016. References of retrieved
      articles were also reviewed and included if applicable. RESULTS: The published
      data are found primarily in the imaging literature and focus on diagnostic
      techniques. Some publications address relationships with diverse, co-existing
      clinical conditions and implications for treatment, especially in stroke,
      intracranial hemorrhage, and antithrombotic therapy. CONCLUSIONS: It is critical
      for non-radiologist clinicians (primary care, internists, neurologists,
      hematologists) to be aware of the potential importance of the finding of a CMB,
      and the fact that these lesions are not always truly silent or without important
      clinical consequences. As additional studies appear, clinicians may be able to
      "hear" more clearly through the silence of the CMB and understand potential
      clinical implications in patients.

PMID- 30193543
TI  - Endoscopic mucosal resection with suction vs. endoscopic submucosal dissection
      for small rectal neuroendocrine tumors: a meta-analysis.
AB  - OBJECTIVE: There are no guidelines or consensus on the optimal treatment measures
      for small rectal neuroendocrine tumors (NETs) at present. This meta-analysis was
      conducted to compare the efficacy and safety of endoscopic mucosal resection
      (EMR) with suction and endoscopic submucosal dissection (ESD) for the small
      rectal NETs. METHODS: The literature searches were conducted using Pubmed and
      Embase databases, and then a meta-analysis was performed. The primary outcome was
      complete resection rate, and the secondary outcomes were complication rate,
      procedure time, and recurrence rate. RESULTS: Fourteen studies with 823 patients
      were included in our meta-analysis. The overall complete resection rates in EMR
      with suction and ESD procedure were 93.65% (472/504) and 84.08% (243/289),
      respectively. The pooled analysis showed that EMR with suction could achieve a
      higher complete resection rate than ESD with significance (OR: 4.08, 95% CI: 2.42
      6.88, p < .00001) when the outlier study was excluded, and procedure time was
      significantly shorter in the EMR with suction group than in the ESD group (SMD: 
      1.59, 95% CI: -2.27 to -0.90, p < .00001). Moreover, there was no significant
      difference in overall complication rate (OR: 0.56, 95% CI: 0.28-1.14, p = .11)
      and overall recurrence rate (OR: 0.76, 95% CI: 0.11-5.07, I2=48%) between EMR
      with suction and ESD group. CONCLUSIONS: The present meta-analysis mostly based
      on retrospective studies show that EMR with suction is superior to ESD for small
      rectal NETs (<=10 mm) with higher complete resection rate, shorter procedure
      time, and similar overall complication rate and recurrence.

PMID- 30193544
TI  - Bridging the Theoretical Gap: Using Sexual Script Theory to Explain the
      Relationship Between Pornography Use and Sexual Coercion.
AB  - Research has consistently shown a relationship between pornography use and
      sexually coercive behaviors, but this inquiry has yet to fully examine the
      theoretical mechanisms through which this relationship works. The current study
      will use a theory that has gained support and attention as a way to understand
      the relationship pornography use has with general sexual behaviors, but has not
      been widely used to explain its relationship with sexually coercive behaviors:
      the sexual script theory. In this theory, scripts are attitudes and ideas about
      what behavior is acceptable, desirable, and pleasurable, which exist at the
      societal, personal, and interpersonal levels. Using items that assess all three
      levels of sexual scripts, a path analysis was used to examine whether sexual
      scripts mediate the relationship between pornography use and sexual coercion
      likelihood in a sample of 463 college males. Results of the study provide further
      support for the theory as a way to explain the relationship between pornography
      use and sexual behavior, and, in particular, sexually coercive behavior. Findings
      from the analysis also indicate that the various levels of scripts interact with
      each other and work together to influence likelihood of sexual coercion,
      providing further insight into how sexual scripts are manifested in behavior.
      Finally, the results suggest that pornography use is a multidimensional construct
      comprised of variables extending beyond frequency of use, such as number of
      modalities used to view pornography. Future research should continue this line of
      inquiry, expanding on the operationalization of sexual scripts and pornography
      use, to strengthen these findings and better illuminate the theoretical
      understanding of the relationship between pornography use and sexual coercion.

PMID- 30193545
TI  - How Thai Women Manage Living in the Context of Intimate Partner Violence.
AB  - Although there is literature that describes coping strategies of women who
      experience intimate partner violence (IPV), the definitions of common coping
      strategies and the two-dimensional model of coping styles (emotion-or problem
      focused) may not fully delineate how these women manage their day-to-day lives.
      Using an Interpretive Description method and feminist standpoint principles, in
      depth interviews were conducted with 40 Thai women regarding how they managed
      living in the context of IPV. Data were analyzed using an iterative thematic
      analysis procedure. In this study, the highly changeable and adaptive strategies
      use by participants could not be easily categorized into emotion-or
      action/problem-focused. Indeed, the strategies used by Thai women in this study
      were better described as survival focused. Based on our analysis, the process of
      managing their day-to-day life in the context of IPV revealed six major themes:
      keeping silent, disconnect between the fantasy of love and reality, seeking
      emotional support, ambivalence surrounding leaving, living with negative
      emotions, and despair and suicide. An undercurrent that was woven throughout
      multiple themes was the dominant lens of motherhood through which women made day
      to-day decisions. These data also highlight the specific impacts that Thai
      society and religious beliefs have on increasing the risk of IPV and maintaining
      its duration. All levels of government, religious leaders, and public policy
      makers must engage in intersectoral initiatives to make public what is now
      private. Social and health service providers must create safe spaces where women
      can disclose IPV and where they can get funded multilevel supports to help them
      live independent of violence. The participants' stories give voice to why Thai
      health professionals need to fully engage with women to understand the past and
      current contexts of women's lives and how their experiences impact their health.

PMID- 30193546
TI  - Differentiating Characteristics of Intimate Partner Violence: Do Relationship
      Status, State, and Duration Matter?
AB  - A growing body of literature has been devoted to analyzing the relationship
      status and state between victim and perpetrator to understand the dynamics of
      intimate partner violence (IPV). Prior research revealed that IPV was more
      frequent and severe in cohabiting and estranged relationships relative to
      marital/dating and intact relationships, respectively. Violence in cohabiting
      unions, however, has declined in recent years potentially due to the increasing
      popularity of such unions and their growing similarity to legal marriages. The
      use of relationship duration as a focal variable in analyzing the characteristics
      of IPV incidents, however, has received inadequate attention within the field.
      This study addresses this gap and builds upon existing research by exploring
      whether characteristics of IPV differ depending on the status, state, and
      duration of relationship by examining IPV cases documented in Crown Attorney
      files in one Ontario jurisdiction between 2003 and 2009. Through bivariate and
      multivariate analyses, current findings reveal that IPV involving marital,
      compared with dating, unions is more severe because of weapon use. Contradictory
      to previous research, IPV occurring among estranged intimate partners, compared
      with those in intact unions, is less likely to involve physical injury or weapon
      use. Finally, situational, in comparison with demographic, characteristics are
      affected less by the relationship duration between the perpetrator and victim.
      Several explanations for these findings are discussed along with study
      limitations and practical implications in terms of preventive measures, and it
      concludes with areas for future research.

PMID- 30193547
TI  - Association of vitamin D status and the risk of cardiovascular disease as
      assessed by various cardiovascular risk scoring systems in patients with type 2
      diabetes mellitus.
AB  - OBJECTIVE: The aim of the present study was to evaluate the relationship between
      vitamin D (25[OH]D) status and the risk of cardiovascular disease as assessed by
      various cardiovascular risk scoring systems such as QRISK2, BNF, ASSING, SCORE,
      and Framingham in patients with type 2 diabetes mellitus(T2DM). METHODS: The
      study included 108 patients with vitamin D insufficiency (25[OH]D >= 10-30 ng/mL)
      and 100 patients with vitamin D deficiency (25[OH]D < 10 ng/mL), who were
      admitted to the diabetes outpatient clinics due to T2DM and who were aged 45-65
      years. QRISK2, BNF, ASSING, SCORE, and Framingham were calculated and compared
      between the two groups. RESULTS: HbA1c levels were significantly higher in
      patients with vitamin D deficiency. Patients with vitamin D deficiency had
      significantly higher Framingham risk score (p < .001) and significantly lower BNF
      score (p < .001), whereas other scores did not significantly differ between the
      groups. There was a moderate, statistically significant correlation between
      25[OH]D levels and Framingham risk score in negative direction (r = 0.537) and a
      weak but statistically significant correlation between 25[OH]D levels and BNF
      score (r = 0.295). 25[OH]D levels were significantly higher and HbA1c levels were
      significantly lower in patients with Framingham cardiovascular risk score <=10%.
      CONCLUSION: We found a close relationship with Framingham cardiovascular risk
      score in diabetic patients with very low serum vitamin D levels. Cardiovascular
      risk as assessed by the Framingham's scale increases with decreasing 25[OH]D
      levels. BNF score was negatively correlated with 25[OH]D levels.

PMID- 30193548
TI  - Sleep in Teens With Type 1 Diabetes: Perspectives From Adolescents and Their
      Caregivers.
AB  - PURPOSE: The purpose of this study is to identify barriers, facilitators, and
      consequences of obtaining sufficient sleep in adolescents with type 1 diabetes.
      METHODS: Semistructured interviews were conducted with 25 adolescents (52%
      female, mean age = 15.6 years) and 25 caregivers. Interviews were transcribed and
      coded using Atlas.ti. A thematic analytic approach was used to identify and
      organize significant patterns of meaning (themes) and interpret themes across the
      data. RESULTS: Several barriers were identified, with the most common being the
      use of electronics before bed and sleep disturbances related to diabetes
      management. Caregivers described strategies for helping adolescents achieve
      sufficient sleep, such as enforcing bedtimes and limiting distractions, but many
      adolescents could not identify facilitators of sleep. Weekday/weekend
      discrepancies in sleep timing were commonly disclosed. CONCLUSIONS: This study is
      the first to examine the perceptions of barriers and facilitators to obtaining
      sufficient sleep in adolescents with T1D and their caregivers. Results have the
      potential to inform providers' recommendations regarding sleep, including
      possible interventions to promote sleep in this high-risk population.

PMID- 30193549
TI  - Hybrid atherectomy for lower extremity peripheral arterial disease.
AB  - Objective To evaluate the effectiveness of directional atherectomy with a Phoenix
      atherectomy system in lower extremity peripheral arterial disease (LE-PAD).
      Materials and methods A retrospective review of subjects who had undergone
      atherectomy for severe and occluded LE-PAD. Demographic data, procedural
      properties, and follow-up information were recorded. The technical, procedural
      and clinical successes were reported. Results In total, 120 subjects were
      evaluated. The superficial femoral artery (SFA) group consisted of 64 subjects
      (53.3%), and the popliteal group consisted of 56 (46.7%) subjects. Groups did not
      differ in terms of age, gender, comorbid diseases and tobacco use. In both
      groups, four subjects (6.3% of SFA and 7.1% of the popliteal group) experienced
      extravasation was encountered in from the vessel during the procedure. During
      atherectomy, two (3.3%) of the subjects in the SFA group and one (1.9%) subject
      in the popliteal group experienced vessel dissection. Acute technical success in
      this study was 96.7% for SFA and 98.1% for the popliteal group. Overall technical
      success was 97.7%. In the first 72 h, three (5%) of the subjects in the SFA group
      and four (7.7%) of the subjects in the popliteal group experienced major adverse
      events. Acute procedural success in this study was 91.7% for SFA and 90.4% for
      the popliteal group. Overall procedural success was 91.1%. Success was defined as
      an improvement of at least one grade in the Rutherford classification; two (3.3%)
      subjects did not demonstrate improvements in the SFA group, and the clinical
      success rate was 96.7%. All subjects in the popliteal group demonstrated an
      improvement of at least one grade in the Rutherford classification, and clinical
      success was 100%. When the groups combined all subjects, the clinical success in
      this study was 98.2%. Conclusion Directional atherectomy with a Phoenix
      atherectomy system demonstrated comparable results with the literature.

PMID- 30193550
TI  - The different scenarios of urgent carotid revascularization for crescendo and
      single transient ischemic attack.
AB  - Objective Carotid stenosis with crescendo-transient-ischemic-attack (cTIA)
      requires a prompt intervention to reduce the stroke risk. Few data are reported
      in literature about cTIA suggesting a different perioperative risk compared with
      patients with single TIA (sTIA). This study aimed to compare the outcome of
      carotid endarterectomy (CEA) in patients with TIA (single/crescendo) and evaluate
      the outcome risk-factors. Methods Data from two tertiary hospitals for vascular
      treatment were analyzed from 2007 to 2016. All patients with TIA subjected to CEA
      were considered, comparing the 30-day postoperative stroke and stroke/death in
      patients with cTIA and sTIA, particularly in the urgent (<=48 h) setting. Results
      On a total of 3866 CEA, 888 (23%) were performed in symptomatic patients and 515
      for TIA: 365 (71%) patients with sTIA and 150 (29%) with cTIA. When compared with
      sTIA, cTIA patients were younger and less frequently affected by coronary
      disease, dyslipidemia, and chronic pulmonary disease; however, contralateral
      carotid occlusion was more common (20% vs. 10%, P = .004; 56% vs. 46, P = .03;
      16% vs. 7%, P = .01; >80 years 26% vs. 16%, P = .01 and 2% vs. 10%, P = .001;
      respectively). Postoperative stroke and stroke/death were significantly higher in
      cTIA compared with sTIA (5.3% vs. 1.6%, P = .02 and 6.0% vs. 2.2%, P = .03;
      respectively). Urgent CEA was performed in 58% ( n: 87) cTIA and in 11% ( n: 56)
      sTIA( P<.01). The urgent setting did not influence the stroke and stroke/death
      rate of CEA for sTIA (3.6% vs. 1.3%, P = .21 and 3.6% vs. 1.9%, P = .44,
      respectively), but was associated with lower rate of events in cTIA (1.1%vs.
      11.1%, P = .01 and 2.3% vs. 11.1%, P = .03, respectively). This beneficial effect
      in patients with cTIA treated within 48-h was confirmed also by multivariate
      analysis (OR: 0.09, 95% CI: 0.76-0.01, P=.02). Conclusions cTIA subjected to CEA
      have a higher stroke and stroke/death risk compared with patients with sTIA. The
      urgent setting seems to reduce the stroke/death rate cTIA; for sTIA with a stable
      neurological condition, the timing of CEA did not influence the outcome.

PMID- 30193551
TI  - Initial outcomes of endovenous laser ablation with 1940 nm diode laser in the
      treatment of incompetent saphenous veins.
AB  - Objectives To investigate the initial outcomes of 1940 nm diode laser in the
      treatment of incompetent saphenous veins. Methods This was a prospective
      observational study. We treated 89 patients with 160 incompetent saphenous veins
      using a 1940 nm diode laser and bare fiber. The laser's power was set to 4.5 W
      with a mean linear endovenous energy density of 50.4 J/cm. Results The one-month
      closure rate was 100%. The post-procedural pain score at 6 h, 1 day, 10 days, and
      1 month was 0.85 +/- 1.04, 0.65 +/- 1.01, 0.82 +/- 1.25, and 0.47 +/- 0.82,
      respectively. Complications encountered included paresthesia (3.8%) and
      thrombophlebitis (4.4%), whereas no cases of endovenous heat-induced thrombosis
      were observed. Conclusion The 1940 nm laser and bare fiber at 50.4 J/cm showed
      satisfactory initial outcomes with less pain and fewer complications, in the
      treatment of incompetent saphenous veins.

PMID- 30193552
TI  - Contemporary trends and outcomes of thrombolytic therapy for acute lower
      extremity ischemia.
AB  - Objective Acute limb ischemia is a common vascular emergency requiring immediate
      intervention. Thrombolysis has been widely utilized for acute limb ischemia; the
      purpose of this study is to analyze contemporary trends, outcomes and
      complications of thrombolysis for acute limb ischemia. Methods Patients were
      identified from the Nationwide Inpatient Sample (2003-2013) using ICD-9. Patients
      undergoing emergency thrombolysis for acute limb ischemia were evaluated. Three
      groups were analyzed: thrombolysis alone, thrombolysis and endovascular procedure
      (T+ENDO), and failed thrombolysis requiring open surgery (T+OPEN). Results A
      total of 162,240 patients with acute limb ischemia were estimated: 33,615
      patients (20.7%) underwent thrombolysis as the initial treatment. Mean age was
      66.2 +/- 34.9 years with 54% male. The utilization of thrombolysis increased
      significantly during the study period (16.8-24.2%, p < 0.0001). The most common
      group was thrombolysis and endovascular procedure (40.7%), followed by
      thrombolysis alone (34.1%), and T+OPEN (25.2%). Thrombolysis and endovascular
      procedure increased significantly over time (31.6-47.8%, p < 0.0001) whereas
      thrombolysis alone and T+OPEN significantly decreased (39.6-28.6% and 28.7-23.6%,
      respectively, p < 0.0001). Overall mortality was 4.9%; thrombolysis and
      endovascular procedure compared to thrombolysis alone and T-OPEN had a lower
      mortality rate (3.2% vs. 6.1% and 5.9%, p < 0001). The overall stroke rate was
      1.9%; thrombolysis alone had the highest stroke rate (3.0%, p < 0.0001) with
      thrombolysis and endovascular procedure the lowest (1.2%) and T+OPEN 1.7%. The
      highest amputation rate was T+OPEN (11.6%, p < 0.001) compared to thrombolysis
      and endovascular procedure (5.1%) and thrombolysis alone (5.3%). T+OPEN had the
      highest incidence of cardiac (5.5%), respiratory (7.3%) and renal complications
      (12.5%), pneumonia (4.0%), and fasciotomy (16.8%) (all p < 0.0001). Conclusion
      Thrombolysis remains an effective treatment for acute limb ischemia with
      increased utilization over time. There was a significant increase in thrombolysis
      and endovascular procedure leading to improved outcomes. Thrombolysis alone
      carried the highest mortality and stroke rate, with T+OPEN associated with the
      highest amputation and complications. Although thrombolysis is effective, 25% of
      patients required an open procedure suggesting that patient selection for
      thrombolysis first instead of open surgery continues to be a clinical challenge.

PMID- 30193553
TI  - Functional prognosis of critical limb ischemia and efficacy of restoration of
      direct flow below the ankle.
AB  - Objective Patients with critical limb ischemia have serious systemic
      comorbidities and are at high risk of impairment of limb function. In this study,
      we assessed the prognostic factors of limbs after revascularization. Methods In
      this retrospective single-center cohort study, from April 2008 to December 2012,
      we treated 154 limbs of 121 patients with critical limb ischemia by the
      endovascular therapy-first approach based on the patients' characteristics. The
      primary end point was amputation-free survival. Secondary end points were patency
      of a revascularized artery, major adverse limb events, or death. Furthermore, we
      investigated the ambulatory status one year after revascularization as prognosis
      of limb function. Results Endovascular therapy was performed in 85 limbs in 65
      patients as the initial therapy (endovascular therapy group) and surgical
      reconstructive procedures (bypass group) were performed in 69 limbs in 56
      patients. Early mortality within 30 days was not observed in either group. The
      primary patency rate was significantly better in the bypass group than in the
      endovascular therapy group ( p < 0.0001). Furthermore, the secondary patency rate
      was similar between the two groups ( p = 0.0096). There were no significant
      differences in amputation-free survival and major adverse limb event between the
      two groups. Univariate analysis showed that ulcer healing ( p < 0.0001), no
      hypoalbuminemia ( p = 0.0019), restoration of direct flow below the ankle ( p =
      0.0219), no previous cerebrovascular disease ( p = 0.0389), and Rutherford 4 ( p
      = 0.0469) were predictive factors for preservation of ambulatory status one year
      after revascularization. In multivariate analysis, ulcer healing ( p < 0.0001)
      and restoration of direct flow below the ankle ( p = 0.0060) were significant
      predictors. Conclusions Ulcer healing and restoration of direct flow below the
      ankle are independently associated with prognosis of limb functions in patients
      who undergo infrainguinal arterial reconstruction.

PMID- 30193554
TI  - The Effects of a 12-Week Combined Exercise Training Program on Arterial
      Stiffness, Vasoactive Substances, Inflammatory Markers, Metabolic Profile, and
      Body Composition in Obese Adolescent Girls.
AB  - PURPOSE: Childhood and adolescent obesity is a major international public health
      crisis. It is crucial to prevent the negative effects of obesity at an early age
      by implementing appropriate lifestyle interventions, such as exercise training.
      We evaluated the effects of a combined resistance and aerobic exercise training
      (CET) regimen on arterial stiffness, vasoactive substances, inflammatory markers,
      metabolic profile, and body composition in obese adolescent girls. METHODS: A
      total of 30 obese adolescent girls were randomly assigned to a CET (n = 15) or a
      control group (n = 15). The CET group trained for 3 days per week. Plasma nitric
      oxide, endothelin-1, C-reactive protein, arterial stiffness, glucose, insulin,
      the adiponectin/leptin ratio, and body fat were measured before and after 12
      weeks. RESULTS: There were significant increases (P < .05) in nitric oxide (4.0
      MUM) and adiponectin/leptin ratio (0.33); and decreases (P < .05) in arterial
      stiffness (-1.0 m/s), C-reactive protein (-0.5 mg/L), glucose (-1.2 mmol/L),
      insulin (-17.1 MUU/mL), and body fat (-3.6%) following CET compared with control.
      There were no significant changes in endothelin-1 after CET or control.
      CONCLUSIONS: The findings of this study indicate that CET improves arterial
      stiffness, nitric oxide, and inflammatory and metabolic markers in obese
      adolescent girls. CET may have important health implications for the prevention
      of atherosclerosis at an early age.

PMID- 30193555
TI  - The Effects of Knee Joint Angle and Contractor Intensity on Perceived Exertion.
AB  - This study examined knee joint angle and knee muscle contraction intensity
      effects on perceived exertion during isometric contractions. Fourteen healthy
      young adults participated in five experimental exercise sessions in which knee
      angles varied randomly (10 degrees , 30 degrees , 50 degrees , 70 degrees , and
      90 degrees ), each separated by one week. During each session, subjects performed
      five isometric maximal voluntary contractions (MVCs) of knee extension, followed
      by nine, randomly ordered submaximal contractions (10%-90% MVC, 10% increments).
      The participants repeated the identical procedure for the knee flexor muscles.
      Immediately following each submaximal contraction, participants rated their
      perceived exertion using a modified Borg category-ratio scale. We found that the
      participants' overall ratings of perceived exertion were significantly ( p < .05)
      greater at the 90 degrees  than at the 70 degrees  and 10 degrees  positions
      during the knee extensor contractions. There were also several significant angle
      by contraction intensity interactions in that perceived exertion was
      significantly greater across 60% to 70% MVC at 30 degrees  than at 50 degrees  (
      p < .01), while the opposite pattern was observed across 70% to 80% MVC ( p <
      .01). During knee flexor contractions, perceived exertion was significantly
      greater ( p < .05) at 90 degrees , when compared with all other knee angles.
      There were also significant ( p < .05) angle by contraction intensity
      interactions between the 50 degrees  and 70 degrees  knee positions across
      contraction intensities of 30-40%, 40-50%, 50-60%, and 60-70% MVC. We conclude
      that the higher perceived exertion rating at 90 degrees  during knee extension
      and flexion contractions suggests different peripheral and central contributors
      between both muscle groups, due to differences in muscle length.

PMID- 30193556
TI  - An Older Adult Study of Concurrent Visual Feedback in Learning Continuous
      Balance.
AB  - This investigation manipulated concurrent visual feedback for older adults
      learning to perform a continuous balance task. We randomly assigned 21 older
      adults to one of three knowledge of results (KR) groups with varying concurrent
      but always 100% terminal feedback percentages during acquisition: 100% Concurrent
      and Terminal (100% C&T), 50% Concurrent and 100% Terminal (50% C & 100% T), and
      0% Concurrent and 100% Terminal (0% C & 100% T). The continuous balance task
      involved learning to maintain balance on a circular platform that moved
      simultaneously on both anterior/posterior and medial/lateral axes. We tested
      participants before acquisition phase learning and two days afterwards (retention
      test). At retention testing, participants in the 50% C & 100% T and those in the
      0% C & 100% T conditions demonstrated significantly greater accuracy and
      stability than did participants in the 100% C&T condition. These findings extend
      previous research with young adults in supporting the guidance theory that too
      frequent a provision of concurrent knowledge of results negatively affects
      learning.

PMID- 30193557
TI  - Electrostatic interaction-mediated conformational changes of adipocyte fatty acid
      binding protein probed by molecular dynamics simulation.
AB  - Adipocyte fatty acid binding protein (A-FABP) is a potential drug target for
      treatment of diabetes, obesity and atherosclerosis. Molecular dynamics (MD)
      simulations, principal component (PC) analysis and binding free energy
      calculations were combined to probe effect of electrostatic interactions of
      residues R78, R106 and R126 with inhibitors ZGB, ZGC and IBP on structural
      stability of three inhibitor/A-FABP complexes. The results indicate that mutation
      R126A produces significant influence on polar interactions of three inhibitors
      with A-FABP and these interactions are main force for driving the conformational
      change of A-FABP. Analyses on hydrogen bond interactions show that the decrease
      in hydrogen bonding interactions of residues R126 and Y128 with three inhibitors
      and the increase in that of K58 with inhibitors ZGC and IBP in the R126A mutated
      systems mostly regulate the conformational changes of A-FABP. This work shows
      that R126A can generate a significant perturbation on structural stability of A
      FABP, which implies that R126 is of significance in inhibitor bindings. We expect
      that this study can provide a theoretical guidance for design of potent
      inhibitors targeting A-FABP. Communicated by Ramaswamy H. Sarma.

PMID- 30193558
TI  - Does Wearing a Portable Metabolic Unit Affect Youth's Physical Activity or
      Enjoyment During Physically Active Games or Video Games?
AB  - : Portable metabolic units (PMUs) are used to assess energy expenditure, with the
      assumption that physical activity level and enjoyment are unaffected due to the
      light weight and small size. PURPOSE: To assess differences in physical activity
      level and enjoyment while wearing and not wearing a PMU. METHOD: Youth (8-17 y; N
      = 73) played children's games or active video games while wearing and not wearing
      a PMU (crossover design). Participants wore an accelerometer and heart rate
      monitor and responded to questions about enjoyment on a facial affective scale. A
      repeated-measures analysis of variance was used to determine if accelerometer
      measures, heart rate, or enjoyment differed between conditions overall and by sex
      and weight status. RESULTS: Steps per minute were lower while wearing the PMU
      than not wearing the PMU (40 vs 44, P = .03). There was an interaction between
      PMU condition and weight status for enjoyment (P = .01), with overweight
      participants reporting less enjoyment when wearing the PMU compared with not
      wearing the PMU (72 vs 75 out of 100). Heart rate, vector magnitude, and counts
      per minute were not different. CONCLUSION: There may be psychosocial effects of
      wearing the PMU, specifically in overweight participants. Activity level was
      minimally affected, but the practical significance for research is still unknown.

PMID- 30193559
TI  - Student Motivation in High School Physical Education: A Latent Profile Analysis
      Approach.
AB  - Guided by the principles of self-determination theory, the purpose of this study
      was to identify latent profiles representing high school students' motivational
      regulations for physical education (PE) and to model putative predictors and
      outcomes of profile membership. A sample of 532 Australian high school students,
      age 12-16 years (M = 13.83, SD = 1.13), reported their motivation for PE,
      perceptions of need satisfaction in PE, and effort expended in PE. Latent profile
      analysis revealed evidence of 3 distinct profiles that were consistent with
      continuum expectations outlined in self-determination theory (i.e., the
      moderately autonomous, moderately controlled, and highly autonomous profiles),
      alongside 2 profiles characterized by levels of introjected regulation that
      aligned with autonomous motives (i.e., the mixed motivation and amotivated
      profiles). Analyses also revealed that, on the whole, greater need satisfaction
      predicted membership of more autonomous profiles and that membership of such
      profiles was predictive of greater self-reported effort in PE. Analyses revealed
      evidence of qualitatively distinct motivation profiles that were differentially
      predicted by students' psychological need satisfaction and predictive of in-class
      effort. This study is not only the first to use latent profile analysis to
      explore the role of psychological need satisfaction in predicting PE motivation
      profiles. It also provides practical information regarding the prevalence and
      potential outcomes of students' motivation profiles.

PMID- 30193561
TI  - Massive Perivillous Fibrin Deposition of an Enterovirus A-Infected Placenta
      Associated With Stillbirth: A Case Report.
AB  - Massive perivillous fibrin deposition (MFD) is a morphologically defined severe
      placental lesion associated with perinatal morbidity and mortality. The etiology
      is unknown, and recurrence risk in subsequent pregnancies is assumed to be high.
      In most cases, a pathologic immune reaction is supposed to be responsible for the
      lesion. We report a case of a pregnant woman's suffering from hand, foot, and
      mouth disease in the 20th gestational week. Subsequently, MFD developed in the
      placenta and was followed by intrauterine growth restriction and stillbirth in
      the 29th gestational week. Enterovirus A with high homology to Coxsackievirus A16
      was detected in the placenta by means of immunohistochemisty and reverse
      transcription polymerase chain reaction. This infection could be a rare cause of
      MFD and should be taken into consideration in the differential diagnosis of the
      individual etiology. Recurrence risk of virus-related MFD is expected to be lower
      than in MFD without infectious association.

PMID- 30193562
TI  - Pathology of Neonatal Non- albicans Candidiasis: Autopsy Study and Literature
      Review.
AB  - Introduction/Objectives Non- albicans Candida species such as Candida
      parapsilosis and Candida glabrata have emerged as prevalent pathogens in
      premature infants. The aim of this study was to systematically delineate the
      histopathologic findings in neonatal non- albicans candidiasis. Methods We
      performed a retrospective clinicopathologic analysis of extremely premature (23
      28 weeks' gestation) infants diagnosed with invasive candidiasis. Archival
      autopsy tissues were subjected to periodic acid-Schiff, methenamine-silver and
      anti- Candida (immuno)histochemical stains, as well as dual anti- Candida and
      anti-cytokeratin or anti-CD31 immunofluorescence assays. In addition, we studied
      the prevalence of intestinal Candida colonization in a consecutive autopsy series
      of extremely premature infants. Results Based on positive postmortem blood and/or
      lung cultures, invasive candidiasis (3 non- albicans and 11 Candida albicans) was
      diagnosed in 14 of the 187 extremely premature infants examined between 1995 and
      2017. In contrast to the well-known inflammatory and tissue-destructive phenotype
      of congenital C. albicans infection, invasive non- albicans
      candidiasis/candidemia caused by C. parapsilosis and C. glabrata was
      inconspicuous by routine hematoxylin-eosin-based histopathologic analysis despite
      a heavy fungal presence detected in intestines, lungs, and blood by targeted
      (immuno)histochemical assays. Intestinal colonization by Candida species was
      identified in 16 of the 26 (61%) extremely premature neonates who had lived for
      at least 1 week, as assessed by anti- Candida immunostaining. Conclusion Invasive
      neonatal non- albicans candidiasis/candidemia appears to have no distinct
      histopathologic signature. Based on the notoriously low sensitivity of fungal
      blood cultures and the observed high frequency of Candida intestinal colonization
      (>50%), it is likely that non- albicans candidiasis/candidemia may be
      underdiagnosed in (deceased) preterm infants. Routine inclusion of targeted
      (immuno)histochemical fungal detection strategies in the perinatal autopsy may
      lead to deeper insight into the prevalence and clinical relevance of neonatal non
      albicans candidiasis.

PMID- 30193563
TI  - Postmortem Diagnosis of Heart-hand Syndrome Associated With a 7p22.1p22.3
      Deletion in a 16-week-old Fetus.
AB  - We report a male fetus with a 6.8 Mb deletion on chromosome 7p22.1p22.3 at 16
      weeks of gestation. The fetus presented a heart-hand syndrome with great artery
      malposition, bilateral radial ray deficiency, a single pelvic kidney, and growth
      retardation. This deletion involves a minimal deleted region for cardiac
      malformation and the RAC1 gene, previously described in limb anomalies in mice.
      This fetus is the third human case with limb defects and RAC1 deletion.

PMID- 30193564
TI  - Impact of telemedicine on the clinical outcomes and healthcare costs of patients
      with chronic heart failure and mid-range or preserved ejection fraction managed
      in a multidisciplinary chronic heart failure programme: A sub-analysis of the
      iCOR randomized trial.
AB  - Background The efficacy of telemedicine in the management of patients with
      chronic heart failure and left ventricular ejection fraction >=40% is poorly
      understood. The aim of our analysis was to evaluate the efficacy of a
      telemedicine-based intervention specifically in these patients, as compared to
      standard of care alone. Methods The Insuficiencia Cardiaca Optimitzacio Remota
      (iCOR) study was a single centre, randomised, controlled trial, designed to
      evaluate a telemedicine intervention added to an existing hospital/primary care
      multidisciplinary, integrated programme for chronic heart failure patients. 178
      participants were randomised to telemedicine or usual care, and were followed for
      six months. For the present sub-analysis, only iCOR participants (n = 116) with
      left ventricular ejection fraction >=40% were included. The primary study
      endpoint was the incidence of an acute non-fatal heart failure event, defined as
      a new episode of worsening of symptoms and signs consistent with acute heart
      failure requiring intravenous diuretic therapy. The healthcare-related costs in
      each study group were also evaluated. Results The incidence of the first
      occurrence of the primary endpoint was significantly lower in the telemedicine
      arm (22% vs 56%, p<0.001), with a hazard ratio of 0.33 comparing to the usual
      care arm (95% confidence interval 0.17-0.64). Telemedicine was also associated
      with lower mean overall chronic heart failure care-related costs compared to
      usual care (8163? vs 4993?, p=0.001). The results were consistent in both left
      ventricular ejection fraction of 40-49% and left ventricular ejection fraction
      >=50% patients. Conclusions Our results suggest that telemedicine is a promising
      strategy for the management of chronic heart failure patients with left
      ventricular ejection fraction >=40%. These findings should be replicated in
      larger cohorts.

PMID- 30193565
TI  - The effect of education through mobile phone short message service on promoting
      self-care in pre-diabetic pregnant women: A randomized controlled trial.
AB  - Introduction Gestational diabetes is increasing in developed and developing
      countries. This study aimed to evaluate the effect of SMS messaging on the self
      care among pre-diabetic pregnant women. Methods This randomized controlled trial
      conducted on 100 pre-diabetic pregnant women referred to Ahvaz Health Centers,
      Iran, Sep to Dec, 2016. Women were randomly assigned into the face to face
      education group and short message systems in addition to the face to face
      education group. Self-care variables were compared between the groups. Data was
      analyzed using chi-square, independent and paired t-tests. Results There was no
      difference regard to FBG and OGTT, but there was a significant difference between
      groups in physical activity level ( P<0.001) and in all food groups except bread
      and cereals after the intervention ( P<0.05). Conclusion The education through a
      short text message system seem couldn't control the blood sugar, but it could
      promote physical activity and food additives of pre-diabetic pregnant women. Key
      words: Self-care, Short message system, Pre-diabetes.

PMID- 30193566
TI  - Sustainable implementation of innovative, technology-based health care practices:
      A qualitative case study from stroke telemedicine.
AB  - Introduction Technology-based innovation requires long-term changes to workforce
      routines, otherwise practices will not be sustained. The aim of this study was to
      identify influential factors in the ongoing use of an acute stroke telemedicine
      programme. Methods A new acute stroke telemedicine programme in a regional
      hospital receiving 375 patients with stroke or transient ischaemic attack per
      year was used as an exploratory case study. Semi-structured interviews with acute
      care and emergency department clinicians ( n = 25) were conducted at two time
      points: after a six-month pilot and then after a further 12-month implementation
      phase. Interviews (between 12-60 min) were recorded, transcribed and analysed
      inductively using descriptive thematic analysis. Reported barriers and
      facilitators were compared with those previously reported pre-implementation
      (deductive analysis) to identify changes over time. Using an implementation
      framework and a behaviour change taxonomy, strategies were developed to address
      influential factors on sustainability. Results New facilitators were identified
      including hospital system changes, benefits to clinicians and telemedicine
      becoming standard practice. New and ongoing barriers included infrequent use,
      competing demands and the continued resistance to a specific treatment.
      Discussion Understanding the factors supporting a health service in successfully
      implementing change can accelerate population benefits. The innovation itself may
      include barriers to be addressed, and barriers and facilitators can change over
      time. Individual attitudes remain critical to initial and ongoing success.
      Strategies proposed included promoting benefits across the organisation and
      allaying uncertainties with site-specific evidence. The effectiveness of these
      strategies, however, needs to be evaluated. Strategies sustaining change post
      implementation should be considered.

PMID- 30193568
TI  - Fasting and time of day independently modulate circadian rhythm relevant gene
      expression in adipose and skin tissue.
AB  - BACKGROUND: Intermittent fasting and time-restricted diets are associated with
      lower risk biomarkers for cardio-metabolic disease. The shared mechanisms
      underpinning the similar physiological response to these events is not
      established, but circadian rhythm could be involved. Here we investigated the
      transcriptional response to fasting in a large cross-sectional study of adipose
      and skin tissue from healthy volunteers (N = 625) controlling for confounders of
      circadian rhythm: time of day and season. RESULTS: We identified 367 genes in
      adipose and 79 in skin whose expression levels were associated (FDR < 5%) with
      hours of fasting conditionally independent of time of day and season, with 19
      genes common to both tissues. Among these genes, we replicated 38 in human, 157
      in non-human studies, and 178 are novel associations. Fasting-responsive genes
      were enriched for regulation of and response to circadian rhythm. We identified
      99 genes in adipose and 54 genes in skin whose expression was associated to time
      of day; these genes were also enriched for circadian rhythm processes. In genes
      associated to both exposures the effect of time of day was stronger and in an
      opposite direction to that of hours fasted. We also investigated the relationship
      between fasting and genetic regulation of gene expression, including GxE eQTL
      analysis to identify personal responses to fasting. CONCLUSION: This study
      robustly implicates circadian rhythm genes in the response to hours fasting
      independently of time of day, seasonality, age and BMI. We identified tissue
      shared and tissue-specific differences in the transcriptional response to fasting
      in a large sample of healthy volunteers.

PMID- 30193567
TI  - Prenatal exposure to bisphenol A and phthalates and behavioral problems in
      children at preschool age: the Hokkaido Study on Environment and Children's
      Health.
AB  - BACKGROUND: Studies reported adverse behavioral development including
      internalizing and externalizing problems in association with prenatal exposure to
      bisphenol A (BPA) and phthalates; however, findings were not sufficient due to
      using different assessment tools and child ages among studies. This study aimed
      to examine associations between maternal serum levels of BPA and phthalate
      metabolites and behavioral problems at preschool age. METHODS: The Strengths and
      Difficulties Questionnaire (SDQ) was used to assess behavioral problems at 5
      years of age. BPA and phthalate metabolite levels in the first trimester maternal
      serum was determined by LC-MS/MS for 458 children. Variables used for adjustment
      were parental ages, maternal cotinine levels, family income during pregnancy,
      child sex, birth order, and age at SDQ completed. RESULTS: The median
      concentrations of BPA, MnBP, MiBP, MEHP, and MECPP, primary and secondary
      metabolites of phthalates, were 0.062, 26.0, 7.0, 1.40, and 0.20 ng/ml,
      respectively. MECPP level was associated with increase conduct problem risk (OR =
      2.78, 95% CI 1.36-5.68) overall and the association remained after child sex
      stratification, and odds ratios were increased with wider confidence interval (OR
      = 2.85, 95% CI 1.07-7.57 for boys, OR = 4.04, 95% CI 1.31-12.5 for girls,
      respectively). BPA, ?DBPm (MnBP + MiBP), and ?DEHPm (MEHP+MECPP) levels were not
      associated with any of the child behavioral problems. CONCLUSIONS: Our analyses
      found no significant association between BPA or summation of phthalate metabolite
      levels and any of the behavioral problems at 5 years of age but suggested
      possible association between MECPP levels and increased risk of conduct problems.

PMID- 30193569
TI  - Prevalence of needlestick and sharps injuries in the healthcare workers of
      Iranian hospitals: an updated meta-analysis.
AB  - BACKGROUND: Needlestick and sharps injuries (NSIs) are critical occupational risk
      among health care workers (HCWs), which is extremely worrying due to the
      potential risk of transmitting bloodborn pathogens (BBPs). This study was carried
      out to evaluate the prevalence of NSIs among Iranian HCWs. METHODS: In this
      systematic review and meta-analysis, the key terms percu* injur*, needle* stick
      injur*, needlestick* injur*, or sharp* injur* were searched in the Scientific
      Information Database (SID), MagIran, IranMedex, Google Scholar, Science Direct,
      PubMed, and Scopus. A prefabricated checklist, including variables: first author,
      publication year, study population, sample size, gender, total prevalence of
      needlestick in each gender, type of questionnaire, region, and type of hospitals,
      was used to extract data from the selected articles included which were published
      between 2003 and 2016. RESULTS: The analysis showed that the prevalence of NSIs
      in the Iranian HCWs was 42.5% (95% CI 37-48). Moreover, the prevalence of NSIs
      was more in women (47%; 95% CI 36-58) compared to men (42%; 95% CI 26-58).
      CONCLUSION: Given the high prevalence of NSIs, it is necessary to supply safe
      needles and instruments, hold training programs focused on new methods of using
      sharp objects safely, observe safety principles and standards, reinforce the
      practical skills of personnel, and pay more attention to reporting and improving
      occupational behaviors like avoiding needle recapping in order to reduce the
      prevalence of NSIs and consequently reduce potential risk of transmission of
      BBPs.

PMID- 30193570
TI  - Optimal viewing angles of intraoperative fluoroscopy for detecting screw
      penetration in proximal humeral fractures: a cadaveric study.
AB  - BACKGROUND: To identify the optimal viewing angles for every proximal screw in
      PHILOS plate-fixed proximal humeral fractures. METHODS: Three fresh-frozen human
      cadaveric bodies with six intact shoulders were studied. All three bodies were
      put in the beach chair position and PHILOS plates were placed on the proximal
      humerus. Head screws penetrating 1 mm into the joint were fitted one by one.
      Fluoroscopy was conducted in the 180 degrees  horizontal plane and the 120
      degrees  coronal plane to analyze each screw's penetration in every shoulder.
      Images were taken every 5 degrees , then all images were analyzed to identify the
      sensitive angles. RESULTS: The range of optimal viewing angles to visualize
      penetration of every head screw was identified. In the coronal plane, the angles
      in the range between 0 degrees  and 10 degrees  were sensitive to all screws
      except No. 8 and No. 9. Furthermore, penetration of screws No. 8 and 9 could not
      be identified on any axillary view, but could be identified in the horizontal
      plane from - 30 degrees  to - 10 degrees  and from 10 degrees  to 35 degrees 
      respectively. CONCLUSIONS: We recommend a 0 degrees -10 degrees  axillary view
      with 30 degrees  arm abduction combined with two horizontal angles in the range
      of - 30 degrees  to - 10 degrees  and 10 degrees  to 35 degrees  for routine
      fluoroscopy during surgery. Our results will be helpful in avoiding primary screw
      penetration.

PMID- 30193571
TI  - Maintaining intraoperative normothermia reduces blood loss in patients undergoing
      major operations: a pilot randomized controlled clinical trial.
AB  - BACKGROUND: Inadvertent intraoperative hypothermia (core temperature < 36 
      degrees C) is a common but preventable adverse event. This study aimed to
      determine whether active intraoperative warming reduced bleeding in patients
      undergoing major operations: open thoracic surgery and hip replacement surgery.
      METHODS/DESIGN: The study was a pilot, prospective, parallel two-arm randomized
      controlled trial. Eligible patients were randomly allocated to two groups:
      passive warming (PW), with application of a cotton blanket (thermal insulation),
      or active warming (AW), with a forced-air warming system. The primary endpoint
      was intraoperative blood loss, and secondary endpoints were surgical-site
      infection, cardiovascular events, and length of stay in the post-anesthesia care
      unit, intensive care unit, and hospital. RESULTS: Sixty-two patients were
      enrolled. Forced-air active warming maintained intraoperative normothermia in all
      AW subjects, whereas intraoperative hypothermia occurred in 21/32 (71.8%) of PW
      patients (p = 0.000). The volume of blood loss was more in the PW group (682 +/-
      426 ml) than in the AW group (464 +/- 324 ml) (p < 0.021), and the perioperative
      hemoglobin value declined more in the PW group (28.6 +/- 17.5 g/L) than in the AW
      group (21.0 +/- 9.9 g/L) (p = 0.045). However, there were no difference in other
      clinical outcomes between two groups. CONCLUSION: Intraoperative active warming
      is associated with less blood loss than passive warming in open thoracic and hip
      replacement operations in this pilot study. TRIAL REGISTRATION: This trial was
      registered with Clinicaltrials.gov (Identifier: NCT02214524 ) on 27 August 2014.

PMID- 30193573
TI  - GP/GPN partner* perspectives on clinical placements for student nurses in general
      practice: can a community of practice help to change the prevailing culture
      within general practice?
AB  - BACKGROUND: The UK Government document 5 year forward view describes the need to
      move chronic disease management from secondary to primary care, which will
      require a significant increase in the numbers of General Practice Nurses (GPNs).
      Until recently, there has been no specific recruitment strategy to address this
      increased need. In recent times, a number of solutions have been suggested to
      address this impending GPN recruitment crisis. For example, Health Education
      England (HEE) commission General Practitioners (GPs), who are members of the
      Advanced Training Practice Scheme (ATPS), to provide placements for student
      nurses within general practice. METHODS: A descriptive qualitative study was
      undertaken, in which data were collected using semi-structured interviews with 16
      GPs and 2 GPN partners*. Qualitative analysis used a framework approach and
      themes were cross-checked within the team and member checking was undertaken with
      a convenience sample of GPs. The research had ethical approval and anonymity and
      confidentiality were maintained. RESULTS: From the GP perspective, there were two
      key themes that emerged from the data. The first theme of 'fishing in the same
      small pond' included succession planning for the general practice workforce, the
      'merry go round' of poaching staff from other practices, and the myths and
      misunderstandings that have grown up around general practice nursing. The second
      theme, 'growing your own', looked at the impact of the student nurse placements
      as a means to address the crisis in GPN recruitment. There was recognition of the
      need for cultural change in the way that GPNs are recruited, and that the ATPS
      was one way of helping to achieve that change. There were however a number of
      challenges to sustaining this cultural shift, such as the financial constrains
      placed upon the GP practice, and the need to function as a 'small business'.
      CONCLUSIONS: Despite all the challenges, the evidence is that, through the
      Community of Practice (CoP), the ATPS scheme is beginning to 'bear fruit', and
      there is a subtle but discernible move by GPs from a 'why would we?' to 'why
      wouldn't we?' invest in education and training for nurses in general practice.
      N.B. The term GPN partner* denotes a GPN who is a 'full partner' in the practice
      business, holding the same NHS contracts and the same status as a GP. For the
      purposes of the paper itself, the term GP will be used to denote both types of
      partner.

PMID- 30193572
TI  - Family physicians perceived role in perinatal mental health: an integrative
      review.
AB  - BACKGROUND: Responding to and caring for women who experience mental health
      problems during the perinatal period, from pregnancy up to one year after birth,
      is complex and requires a multidisciplinary response. Family physicians are
      ideally placed to provide an effective response as it is recognised that they are
      responsible for organising care and supports for women and their families. This
      paper reports an integrative review undertaken to examine family physicians'
      perceived role in perinatal mental health care and concludes with recommendations
      for health policy, research and practice. METHOD: A systematic search of
      literature in seven databases from January 2000 to March 2016 identified a total
      of 1125 articles. Qualitative, quantitative and mixed-method studies were
      eligible for inclusion if they explored family physicians' experiences of caring
      for women who experience perinatal mental health problems. RESULTS: Thirteen
      articles reporting 11 studies met the inclusion criteria for this review and
      quality of included studies were assessed using published criteria for the
      critical appraisal of qualitative and quantitative research methods. Cross-study
      narrative syntheses of quantitative and qualitative findings are presented under
      three themes: identification of perinatal mental health problems, management of
      perinatal mental health problems and barriers to care provision. While family
      physicians recognise their role in relation to perinatal mental health the
      collective interpretation revealed that; they receive variable levels of
      preparation for this role, no consistent approach to screening exists,
      pharmacological management of mood disorders is the main treatment modality and
      limited access to specialist perinatal mental health services exists which
      impacts on pharmacology decisions. CONCLUSION: Family physicians require timely
      access to local integrated care pathways that provide a wide range of services
      that are culturally sensitive, perinatal mental health specific, support
      psychological well-being and infant/family mental health. Family physicians are
      open to incorporating a brief validated screening tool into primary practice
      supported by succinct guidelines. Research that examines training needs in
      relation to perinatal mental health could be used to inform family physician
      training programmes and curriculum development around perinatal mental health.

PMID- 30193574
TI  - Hemodynamic responses to tracheal intubation with Bonfils compared to C-MAC
      videolaryngoscope: a randomized trial.
AB  - BACKGROUND: Direct laryngoscopy (DL) produce tachycardia and hypertension that
      could be fatal in a patient with a brain injury. Bonfils fiberscope and C-MAC
      videolaryngoscope are associated with little hemodynamic instability compared to
      DL. Scientific evidence comparing these two alternatives does not exist. We
      conducted this study to determine the hemodynamic effects of Bonfils compared to
      C-MAC in patients undergoing elective surgery. METHODS: Fifty (50) patients
      listed for elective surgery were randomly assigned to endotracheal intubation
      with Bonfils or C-MAC. After a standardized induction, intubation was done via
      the retromolar approach (Bonfils group) or via videolaryngoscopy (C-MAC group). A
      research assistant, who was not blinded to the intervention, recorded heart rate
      (HR) and arterial blood pressure (systolic, diastolic and mean arterial blood
      pressure [MAP]) at induction and at every minute during the 5 min post
      intubation. The primary outcome was the hemodynamic response to intubation, as
      verified every minute for the first 5 min compared to baseline value. RESULTS:
      After randomization, the two groups were comparable except for ASA I/II ratio
      which was slightly higher in the C-MAC group (p = 0.046). Heart rate (p = 0.40)
      and MAP (p = 0.30) were comparable between the two groups within 5 min post
      intubation. Intubation time was shorter with C-MAC than with Bonfils (30 +/- 2 s
      vs 38 +/- 2 s; p = 0.02). CONCLUSION: Hemodynamic responses to tracheal
      intubation using the Bonfils fiberscope is comparable to the C-MAC
      videolaryngoscope among patients scheduled for an elective surgery. In light of
      these findings, using either technique appears to be a reasonable course of
      action. TRIAL REGISTRATION: ISRCTN #34923 , retrospectively registered,
      26/03/2018.

PMID- 30193575
TI  - Low molecular weight heparin versus other anti-thrombotic agents for prevention
      of venous thromboembolic events after total hip or total knee replacement
      surgery: a systematic review and meta-analysis.
AB  - BACKGROUND: Venous thromboembolism (VTE) is an important complication following
      total hip replacement (THR) and total knee replacement (TKR) surgeries. Aim of
      this study was to comprehensively compare the clinical outcomes of low-molecular
      weight heparin (LMWH) with other anticoagulants in patients who underwent TKR or
      THR surgery. METHODS: Medline, Cochrane, EMBASE, and Google Scholar databases
      were searched for eligible randomized controlled studies (RCTs) published before
      June 30, 2017. Meta-analyses of odds ratios were performed along with subgroup
      and sensitivity analyses. RESULTS: Twenty-one RCTs were included. In comparison
      with placebo, LMWH treatment was associated with a lower risk of VTE and deep
      vein thrombosis (DVT) (P values < 0.001) but similar risk of pulmonary embolism
      (PE) (P = 0.227) in THR subjects. Compared to factor Xa inhibitors, LMWH
      treatment was associated with higher risk of VTE in TKR subjects (P < 0.001), and
      higher DVT risk (P < 0.001) but similar risk of PE and major bleeding in both THR
      and TKR. The risk of either VTE, DVT, PE, or major bleeding was similar between
      LMWH and direct thrombin inhibitors in both THR and TKR, but major bleeding was
      lower with LMWH in patients who underwent THR (P = 0.048). CONCLUSION: In
      comparison with factor Xa inhibitors, LMWH may have higher risk of VTE and DVT,
      whereas compared to direct thrombin inhibitors, LMWH may have lower risk of major
      bleeding after THR or TKR.

PMID- 30193576
TI  - Safety work and risk management as burdens of treatment in primary care: insights
      from a focused ethnographic study of patients with multimorbidity.
AB  - BACKGROUND: In primary health care, patient safety failures can arise in service
      access, doctor-patient relationships, communication between care providers,
      relational and management continuity, or technical procedures. Through the lens
      of multimorbidty, and using qualitative ethnographic methods, our study aimed to
      illuminate safety issues in primary care. METHODS: Data were triangulated from
      electronic health records (EHRs); observation of primary care consultations;
      annual interviews with patients, (informal) care providers and GPs. A thematic
      analysis of observation, interview and field note material sought to describe the
      patient safety issues encountered and any associated factors or processes. A more
      detailed longitudinal description of 6 cases was used to contextualise safety
      issues identified in observation, interviews and EHRs. RESULTS: Twenty-six
      patients were recruited. Events which could lead to harm were found in all areas
      of a framework based on published literature. "Under" and "over" consultation as
      a precursor of safety failures emerged through thematic analysis of observation
      and interview material. Other findings concerned workload (for doctors and
      patients) and the limitations of short consultation times. There were differences
      in health data collected directly from the patients versus that found in EHRs.
      Examples included reference to a stroke history and diagnoses for CKD and
      hypertension. Case study analysis revealed specific issues which appeared
      contextual to safety concerns, mostly around the management of polypharmacy and
      patient medication adherence. Clinical imperatives appear around risk management,
      but the study findings point to a potential conflict with patient expectations
      around investigation, diagnosis and treatment. DISCUSSION: Patient safety work
      involves further burdens on top of existing workload for both clinicians and
      patients. In this conceptualisation, safety work seemingly forms part of a
      negative feedback loop with patient safety itself. A line of argument drawn from
      the triangulation of findings from different sources, points to a tension between
      the desirability of a minimally disruptive medicine versus safety risks possibly
      associated with 'under' or 'over' consultation. Multimorbidity acts as a
      magnifier of tensions in the delivery of health services and quality care in
      general practice. More attention should be put on system design than patient or
      professional behaviour.

PMID- 30193578
TI  - Different lipid profiles, insulin sensitivity, and insulin resistance among Han,
      Uygur, and Kazak men with normal glucose tolerance in Xinjiang, China.
AB  - BACKGROUND: This study aimed to determine the differences in clinical parameters
      among Han, Uygur, and Kazak men with normal glucose tolerance. METHODS:
      Participants' data from the China National Diabetes and Metabolic Disorders Study
      pertaining to Han, Uygur, and Kazak men from the Xinjiang province were used (n =
      930). Pearson's correlation was used to examine the relationship between HOMA-IR,
      Matsuda Index, and clinical characteristics. RESULTS: HOMA-IR of Han men was
      significantly higher than in Uygurs and Kazaks (P < 0.001). The Matsuda Index of
      Kazaks was significantly higher than that of Hans and Uygurs (P < 0.001). While
      Kazaks had the highest BMI, WC, SBP, and DBP; they also had the highest HDL-C and
      lowest TG (P < 0.001). TG of Uygurs was significantly higher than that of Hans
      and Kazaks (P < 0.001). In Hans and Kazaks, the TG/HDL-C ratio increased with
      HOMA-IR quartiles; there was no association in Uygurs. In Hans and Kazaks, the
      TG/HDL-C ratio decreased with Matsuda index quartiles; there was no association
      in Uygurs. Multivariate linear regression showed that HOMA-IR was independently
      associated with ethnicity, BMI and TG/HDL-C ratio (P < 0.01), while Matsuda index
      was independently associated with ethnicity, BMI, LDL-C levels (P < 0.001) and
      TG/HDL-C ratio (P < 0.001). CONCLUSIONS: In conclusion, Han, Uygur, and Kazak men
      had different lipid profiles, BMI, and WC. Han men had the highest insulin
      resistance while Kazak men had the highest insulin sensitivity.

PMID- 30193577
TI  - Mosaic Tetrasomy of 9p24.3q21.11 postnatally identified in an infant born with
      multiple congenital malformations: a case report.
AB  - BACKGROUND: Supernumerary Marker Chromosomes consist in structurally abnormal
      chromosomes, considered as an extra chromosome in which around 70% occur as a de
      novo event and about 30% of the cases are mosaic. Tetrasomy 9p is a rare
      chromosomal abnormality described as the presence of a supernumerary
      isochromosome 9p. Clinical features of tetrasomy 9p include a variety of physical
      and developmental abnormalities. CASE PRESENTATION: Herein, we reported a
      postnatal case of a newborn who died in early infancy with multiple congenital
      malformations due to a mosaic de novo tetrasomy 9p detected by Chromosomal
      Microarray Analysis. Conventional cytogenetics analysis of the proband was
      47,XY,+mar[45]/46,XY[5]. The parental karyotypes presented no visible numerical
      or structural alterations. Microarray Analysis of the proband revealed that the
      marker chromosome corresponded to a mosaic de novo gain at 9p24.3q21.11.
      CONCLUSIONS: Chromosomal Microarray Analysis was helpful to identify the origin
      of the supernumerary marker chromosome and it was a powerful tool to carry out
      genetic diagnostic, guiding the medical diagnosis. Furthermore, the CMA allowed
      observing at the first time in Central Brazil the tetrasomy 9p and partial
      tetrasomy 9q in mosaic, encompassing a large duplicated region with several
      morbid genes, in an infant with multiple congenital malformations.

PMID- 30193579
TI  - Scopolaminebutyl given prophylactically for death rattle: study protocol of a
      randomized double-blind placebo-controlled trial in a frail patient population
      (the SILENCE study).
AB  - BACKGROUND: Death rattle (DR), caused by mucus in the respiratory tract, occurs
      in about half of patients who are in the dying phase. Relatives often experience
      DR as distressing. Anticholinergics are recommended to treat DR, although there
      is no evidence for the effect of these drugs. Anticholinergic drugs decrease the
      production of mucus but do not affect existing mucus. We therefore hypothesize
      that these drugs are more effective when given prophylactically. METHODS: We set
      up a randomized double-blind, placebo-controlled, multi-center study evaluating
      the efficacy of prophylactically given subcutaneous scopolaminebutyl for the
      prevention of DR in the dying phase. The primary outcome is the occurrence of DR
      defined as grade >= 2 according to the scale of Back measured by a nurse at 2
      consecutive time points with an interval of 4 h. Secondary outcomes include
      adverse effects, quality of dying, quality of life in the last three days and
      bereavement. A sub-study will explore the experience of participating in a
      clinical trial in the dying phase from the perspective of relatives. Four
      hospices will include 200 patients. DISCUSSION: This is the first double-blind
      placebo-controlled study to prevent DR in patients in the hospice setting.
      Research in dying patients is challenging. We will apply ethical and
      organizational strategies as suggested in the literature. TRIAL REGISTRATION: The
      trial is retrospectively registered in the Dutch Trial register, identifier NTR
      6438 June 2017. EudractCT number 2016-002287-14.

PMID- 30193581
TI  - Risk of low serum levels of ionized magnesium in children with febrile seizure.
AB  - BACKGROUND: Suboptimal intake of magnesium become prevalent due to the modern
      diet of processed food low in magnesium. Magnesium may modulate seizure activity
      by antagonizing excitatory calcium influx through the N-methyl-D-aspartate
      receptor. Although hyponatremia has been reported to be common in febrile
      seizures, the most common form of seizure, little is known about the status of
      serum ionized magnesium. We therefore investigated the status of serum ionized
      magnesium (iMg2+) in children with febrile seizures and compared with controls.
      METHODS: We included all patients from 1 to 6 years old who had presented with
      febrile seizure to the pediatric emergency department at the Korea University
      Guro Hospital from July 2016 to February 2017. The control group comprised
      patients admitted to the hospital with febrile respiratory tract infections, but
      with no history of febrile seizure. Clinical data, blood tests, and
      electroencephalogram (EEG) results were reviewed using the patients' medical
      records. RESULTS: A total of 133 patients with febrile seizure and 141 control
      patients were analyzed in the present study. As a result, hypomagnesemia (< 0.50
      mmol/L) was more common in patients with febrile seizure than in controls (42.9%
      vs. 6.9%, p < 0.001) and it was an independent risk factor for febrile seizure
      (OR, odds ratio = 22.12, 95% CI = 9.23-53.02, P < 0.001). A receiver operating
      curve analysis revealed that serum iMg2+ levels < 0.51 mmol/L predicted the
      presence of febrile seizures with a sensitivity of 45.1% and a specificity of
      92.6% (AUC, area under the curve = 0.731, 95% confidence interval = 0.671-0.791).
      When the patients with febrile seizure were divided in terms of a serum iMg2+
      concentration of 0.51 mmol/L, there was no difference in clinical features.
      CONCLUSIONS: Hypomagnesemia was more common and serum iMg2+ level was lower in
      patients with febrile seizures than in controls. However, further evidence is
      needed for the causal relationship between low magnesium and febrile convulsions.

PMID- 30193582
TI  - Pancreaticojejunostomy with or without reinforcement after
      pancreaticoduodenectomy: surgical technique of ligamentum teres hepatis wrap
      around pancreaticojejunostomy.
AB  - In a previous issue of the Journal, Zhong et al. reported a retrospective study
      that compared the perioperative outcomes of the mesh-reinforced
      pancreaticojejunostomy with conventional pancreaticojejunostomy. They concluded
      that mesh-reinforced pancreaticojejunostomy was a safe and effective technique,
      as it provided a safe anchor site for suture, thus reducing the risk of
      pancreatic leakage. Considering these encouraging results, we present a further
      simple technique using ligamentum teres hepatis wrap around pancreatojejunostomy
      for prevention of postoperative pancreatic fistula after pancreaticoduodenectomy.

PMID- 30193580
TI  - Somatostatin receptor 2A protein expression characterizes anaplastic
      oligodendrogliomas with favorable outcome.
AB  - Diffuse gliomas are classified according to the 2016 WHO Classification of Tumors
      of the Central Nervous System, which now defines entities by both histology and
      molecular features. Somatostatin receptor subtype 2A (SSTR2A) expression has been
      reported in various solid tumors as associated with favorable outcomes. Its
      expression has been reported in gliomas with uncertain results regarding its
      prognostic value. The objective of this study was to assess the prognostic impact
      of SSTR2A protein expression in a large cohort of grade III and IV gliomas
      classified according to the updated 2016 WHO classification. We further validated
      our result with an independent cohort of low grade glioma using dataset generated
      by The Cancer Genome Atlas (TCGA) Research Network.We analyzed clinical and
      molecular data from 575 patients. SSTR2A protein expression was evaluated using
      immunohistochemistry on tissue microarrays. High expression of SSTR2A protein
      associated with the anaplastic oligodendroglioma IDH-mutant and 1p/19q-codeleted
      subgroup (p < 0.001). Among these tumors, SSTR2A protein expression was
      significantly associated with a lower proliferative index, the absence of
      microvascular proliferation and the absence of necrosis (p < 0.001). Furthermore
      SSTR2A protein expression associated with better overall survival (p = 0.007) and
      progression-free survival (p = 0.01) in both univariate and multivariate analysis
      when adjusted by the age, the presence of necrosis and the mitotic index. Similar
      results were obtained regarding SSTR2 mRNA expression in the TCGA low grade
      glioma, subtype IDH-mutant and 1p/19q-codeleted, dataset.SSTR2A might represent
      an attractive biomarker and therapeutic target in anaplastic oligodendroglioma
      IDH-mutant and 1p/19q-codeleted specific subgroup. Understanding the implicated
      molecular pathways may represent a step forward to improve therapeutic
      approaches.

PMID- 30193583
TI  - Omega 3 polyunsaturated fatty acids inhibit cell proliferation by regulating cell
      cycle in fad3b transgenic mouse embryonic stem cells.
AB  - BACKGROUND: The consumption of omega 3 polyunsaturated fatty acids (PUFAs) is
      important for human health and is closely associated with cell proliferation and
      differentiation. This study aimed to investigate the influence of omega 3 PUFAs
      on embryonic stem cell (ESC) proliferation and explore potential mechanisms that
      mediate these effects. METHODS: In this study, we isolated ESCs from fad3b
      expressing transgenic mice. We detected the fatty-acid composition of ESCs using
      gas chromatography-mass spectroscopy, analyzed cell-cycle phases using flow
      cytometry, and detected gene expression using real-time polymerase chain reaction
      (PCR) and western blots. RESULTS: The amount of omega 3 PUFAs significantly
      increased in fad3b versus control ESCs. However, the growth of fad3b ESCs was
      slower than that of control cells, and most fad3b ESCs were in a prolonged G0/G1
      phase after being passaged for 18 h. Therefore, we hypothesized that fad3b
      expression inhibited the cell cycle in ESCs by increasing the expression of P21,
      which then decreased the expression of cyclin-dependent kinase 4 (Cdk4). We found
      that pretreatment of fad3b ESCs with PD0325901, a P21 inhibitor, clearly
      attenuated the inhibitory effects of P21 on Cdk4, and resumed the cell cycle.
      CONCLUSIONS: Expression of the fad3b gene in ESCs increased the omega 3 PUFA
      content, which inhibited cell proliferation by prolonging the G1 phase but did
      not arrest the G0-to-G1 or G1-to-S transitions. The prolonged G1 phase in fad3b
      ESCs was probably induced by downregulation of Cdk4 expression via p21
      upregulation. These results suggest that accumulation of omega 3 PUFAs in vivo
      may beneficially affect ESC differentiation and that fad3b ESCs may be a useful
      tool for investigating related mechanisms.

PMID- 30193585
TI  - Adverse effects of psychotherapy: protocol for a systematic review and meta
      analysis.
AB  - BACKGROUND: While it is well known that psychotherapy is efficacious in the
      treatment of mental disorders, much less is known about the adverse effects of
      psychotherapeutic interventions. The aim of this systematic review is to examine
      the definition, frequency, nature, and severity of adverse effects occurring
      parallel to or following psychotherapeutic treatment and to compare it against
      control groups. METHODS: All registered randomised controlled trials published
      since 2004 (publication year of harm-reporting extension of the CONSORT
      statement) with adult patients fulfilling clinical criteria of defined mental
      disorders, which compare individual or group psychotherapy against a control
      group, will be included. First, a search through international trial registers as
      well as a search in literature databases (e.g. MEDLINE) and in relevant journals
      (e.g. Trials) for study protocols will be conducted to identify eligible trials.
      In a second step, we will search for respective publications of the results of
      the eligible studies. Publications will be retrieved and screened for
      eligibility. Two previously trained, independent raters will extract the data in
      duplicate. Reporting of adverse effects will be descriptively analysed regarding
      frequency, heterogeneity, and longitudinal course. We will further compare the
      adverse effects of psychotherapeutic interventions against various control
      groups. For each categorical outcome, we will calculate relative risks (RR)
      together with 95% confidence intervals. For continuous outcomes, standardised
      mean differences (Hedges' g) with a 95% confidence interval will be computed.
      Between-study heterogeneity will be tested with the Q statistic and quantified
      using I2. DISCUSSION: Preselecting studies with regard to randomised controlled
      trials might induce bias due to dropout before the beginning of treatment or end
      of treatment. However, we will thoroughly assess the negative effects of
      randomisation, e.g. reasons for non-randomisation, if reported. Even if delayed
      adverse effects might be overlooked in randomised controlled trials, these are
      the only sources of causal evidence. SYSTEMATIC REVIEW REGISTRATION: PROSPERO
      International Prospective Register of Systematic Reviews 2017: CRD42017055507 (17
      January 2017).

PMID- 30193584
TI  - Lipidomic profiling of extracellular vesicles derived from prostate and prostate
      cancer cell lines.
AB  - BACKGROUND: Extracellular vesicles (EVs) are produced and secreted from most
      cells of the body and can be recovered in biological fluids. Although there has
      been extensive characterisation of the protein and nucleic acid component of EVs,
      their lipidome has received little attention and may represent a unique and
      untapped source of biomarkers for prostate cancer diagnosis and prognosis.
      METHODS: EVs were isolated from non-tumourigenic (RWPE1), tumourigenic (NB26) and
      metastatic (PC-3) prostate cell lines. Lipids were extracted and subsequently
      used for targeted lipidomics analysis for the quantitation of molecular lipid
      species. RESULTS: A total of 187 molecular lipid species were quantitatively
      identified in EV samples showing differential abundance between RWPE1, NB26 and
      PC-3 EV samples. Fatty acids, glycerolipids and prenol lipids were more highly
      abundant in EVs from non-tumourigenic cells, whereas sterol lipids, sphingolipids
      and glycerophospholipids were more highly abundant in EVs from tumourigenic or
      metastatic cells. CONCLUSIONS: This study identified differences in the molecular
      lipid species of prostate cell-derived EVs, increasing our understanding of the
      changes that occur to the EV lipidome during prostate cancer progression. These
      differences highlight the importance of characterising the EV lipidome, which may
      lead to improved diagnostic and prognostic biomarkers for prostate cancer.

PMID- 30193586
TI  - The efficacy and safety of combined administration of intravenous and topical
      tranexamic acid in primary total knee arthroplasty: a meta-analysis of randomized
      controlled trials.
AB  - BACKGROUND: The combined administration of intravenous (IV) and topical
      tranexamic acid (TXA) in primary total knee (TKA) knee remains controversial. The
      purpose of this meta-analysis was to assess the efficacy and safety of combined
      administration of IV and topical TXA in primary TKA. METHODS: PubMed, EMBASE,
      Cochrane Central Register of Controlled Trials, Web of Science, Google Search
      Engine and China National Knowledge Infrastructure databases were searched for
      randomized controlled trials (RCTs) were comparing the combined administration of
      IV and topical TXA following primary TKA. The primary outcomes were total blood
      loss, maximum hemoglobin drop, and deep venous thrombosis (DVT) and/or pulmonary
      embolism (PE). The second outcomes were drainage volume and transfusion
      requirements. Data were analyzed using RevMan 5.3. RESULTS: A total of 6 RCTs
      involving 701 patients were included in the meta-analysis. The combined group
      provided lower total blood loss (MD - 156.34 mL, 95% CI, - 241.51 to - 71.18; P =
      0.0003), drainage volume (MD - 43.54 mL, 95% CI, - 67.59 to - 19.48; P = 0.0004),
      maximum hemoglobin drop (MD - 0.56 g/dl, 95% CI, - 0.93 to - 0.19; P = 0.003)
      than IV TXA alone. No significant difference were found in terms of transfusion
      requirements (RR 0.48, 95% CI, 0.16 to 1.44; P = 0.19), DVT (RR 1.01, 95% CI,
      0.14 to 7.12; P = 0.99) and PE (RR 0.33, 95% CI, 0.01 to 7.91; P = 0.49) between
      the two group. Subgroup analyses shows that the combined group was less total
      blood loss in non-tourniquet (P = 0.0008), topical TXA dose > 1.5 g (P < 
      0.00001) and number of IV TXA >= 2 doses (P = 0.005) of TXA compared with the IV
      group alone. CONCLUSIONS: The available evidence indicates combined group were
      associated with lower total blood loss, drainage volume, and maximum hemoglobin
      drop. A similar transfusion requirement was found in both groups. Subgroup
      analyses demonstrates that total blood loss was less in patients with non
      tourniquet, topical TXA dose > 1.5 g and number of IV TXA >= 2 doses of TXA.
      There was no increase the rates of DVT and PE.

PMID- 30193588
TI  - Incidence of tolerance in children undergoing repeated administration of propofol
      for proton radiation therapy: a retrospective study.
AB  - BACKGROUND: Propofol is an excellent hypnotic drug for use in repeated radiation
      procedures in young children. To date, tolerance to propofol generally does not
      develop in pediatric patients undergoing radiation therapy. However, several
      studies have suggested that there may be potential for development of tolerance
      to propofol. The aim of this study was to evaluate the development of a tolerance
      to propofol used for repeated deep sedation in children undergoing proton
      radiation therapy (PRT). METHODS: All children undergoing PRT at our institution
      between December 2015 and January 2018 were eligible for inclusion in this study.
      Sedation was induced by a bolus dose of propofol (2.0 mg.kg- 1) followed by a
      continuous infusion of 250 MUg.kg- 1.min- 1 via an infusion pump to achieve deep
      sedation. Sedation was maintained with the propofol infusion of 200 MUg.kg- 1.min
      1, which was adjusted in 25 MUg.kg- 1.min- 1 increments up or down as necessary
      to ensure deep sedation. The primary outcome was mean doses of propofol over
      time. RESULTS: Fifty-eight children were analyzed. The mean (SD) age was 4.5
      (2.1) years. The mean (SD) number of treatment sessions was 19 (7). Fifteen
      patients (26%) developed tolerance to propofol. However, there were no
      significant differences between the children who developed tolerance and the
      children who did not develop tolerance in mean propofol dose and awakening time
      over time (p = 0.887 and P = 0.652, respectively). Age, the number of PRT, and
      attending anesthesiologists was not significantly associated with the incidence
      of tolerance to propofol. CONCLUSION: Repeated prolonged deep sedation for PRT
      elicited multiple times over several weeks in young children using propofol did
      not develop tolerance in 74% of patients. Although the incidence of 26% tolerance
      to propofol may still be present, the increase in propofol dose was minimal.
      Therefore, the use of repeated propofol for children was safe.

PMID- 30193587
TI  - Systemic infection modifies the neuroinflammatory response in late stage
      Alzheimer's disease.
AB  - Clinical studies indicate that systemic infections accelerate cognitive decline
      in Alzheimer's disease. Animal models suggest that this may be due to enhanced
      pro-inflammatory changes in the brain. We have performed a post-mortem human
      study to determine whether systemic infection modifies the neuropathology and in
      particular, neuroinflammation, in the late-stage of the disease.Sections of
      cerebral cortex and underlying white matter from controls and Alzheimer's
      patients who died with or without a terminal systemic infection were
      immunolabelled and quantified for: (i) Alphabeta and phosphorylated-tau; (ii) the
      inflammation-related proteins Iba1, CD68, HLA-DR, FcgammaRs (CD64, CD32a, CD32b,
      CD16), CHIL3L1, IL4R and CCR2; and (iii) T-cell marker CD3. In Alzheimer's
      disease, the synaptic proteins synaptophysin and PSD-95 were quantified by ELISA,
      and the inflammatory proteins and mRNAs by MesoScale Discovery Multiplex Assays
      and qPCR, respectively.Systemic infection in Alzheimer's disease was associated
      with decreased CD16 (p = 0.027, grey matter) and CD68 (p = 0.015, white matter);
      increased CD64 (p = 0.017, white matter) as well as increased protein expression
      of IL6 (p = 0.047) and decreased IL5 (p = 0.007), IL7 (p = 0.002), IL12/IL23p40
      (p = 0.001), IL15 (p = 0.008), IL16 (p < 0.001) and IL17A (p < 0.001). Increased
      expression of anti-inflammatory genes CHI3L1 (p = 0.012) and IL4R (p = 0.004)
      were detected in this group. T-cell recruitment to the brain was reduced when
      systemic infection was present. However, exposure to systemic infection did not
      modify the pathology. In Alzheimer's disease, CD68 (p = 0.026), CD64 (p = 0.002),
      CHI3L1 (p = 0.016), IL4R (p = 0.005) and CCR2 (p = 0.010) were increased
      independently of systemic infection.Our findings suggest that systemic infections
      modify neuroinflammatory processes in Alzheimer's disease. However, rather than
      promoting pro-inflammatory changes, as observed in experimental models, they seem
      to promote an anti-inflammatory, potentially immunosuppressive, environment in
      the human brain.

PMID- 30193589
TI  - A systematic search and qualitative review of reporting bias of lifestyle
      interventions in randomized controlled trials of diabetes prevention and
      management.
AB  - BACKGROUND: Scholars have documented presumptions regarding the relationships
      between diet, exercise, weight, and type 2 diabetes. However, it is unclear to
      what extent researchers contribute to these presumptions, and how often these
      relationships are thoroughly delineated within the context of randomized
      controlled trials (RCTs). Thus, the aim was to conduct a systematic search and
      qualitative, thematic analysis of RCTs focusing on lifestyle interventions for
      diabetes prevention or management, to examine how researchers discuss body weight
      in 1) the rationale and design of their RCTs; and 2) their presentation and
      interpretation of their findings. METHODS: We completed an electronic search for
      records published between 2007 and November 2016. Selection criteria included:
      RCTs with a follow-up period of >=12 months; adult participants with type 2
      diabetes/pre-diabetes; lifestyle interventions classified as dietary, exercise,
      and/or behavioural; primary outcomes of incident diabetes and complications,
      mortality, cardiovascular disease, and quality of life; and secondary outcomes of
      glycemic control and blood pressure. Nineteen articles were identified for
      inclusion and subject to thematic content analysis. RESULTS: Obesity and weight
      loss figured prominently in the rationale and outcomes of the majority of the
      articles, despite intentional exclusion of "weight loss" and "obesity" as search
      terms. There was ambiguity over whether weight loss was classified as inclusive
      to the intervention, an outcome, or a measure of adherence. Results revealed that
      authors frequently engaged in "spin reporting" by pooling data from intervention
      and control groups to test the relationship between weight lost and outcomes and
      in their presentation of results. CONCLUSIONS: Researchers need to be aware of
      their biases and assumptions regarding body weight in designing, analyzing, and
      interpreting lifestyle interventions for diabetes prevention and management.

PMID- 30193591
TI  - Trigeminal neuralgia associated with ophthalmic surgery: a case series.
AB  - BACKGROUND: Trigeminal neuralgia is a rare cause of postoperative pain after
      ophthalmic surgery and has only been described twice in the international
      literature: one case of pain after vitrectomy with a crystalline lens extraction
      and another case of an unspecified surgery type. We report three cases of
      ophthalmic surgery-induced trigeminal neuralgia. CASE PRESENTATION: Trigeminal
      neuralgia was diagnosed in three patients after ophthalmic surgery. Patient 1 was
      a 63-year-old Caucasian man with an epiretinal membrane and cataract in his left
      eye. Phacovitrectomy was performed. Patient 2 was a 38-year-old Caucasian man
      with a perforating wound in his right eye. Primary closure of the cornea with
      removal of the necrotic iris was performed. Patient 3 was a 52-year-old Caucasian
      man referred 15 days after suffering blunt trauma to his right eye. Vitrectomy
      was performed to remove the crystalline lens, which was luxated to the vitreous.
      On postoperative days, these three patients were admitted to an emergency ward
      due to sudden, shock-like, one-sided facial pain activated by numerous stimuli.
      After consultation with specialists from the anesthesia and neurology
      departments, a diagnosis of trigeminal neuralgia was made. This diagnosis was
      based on the presence of four of the nine clinical criteria described by the
      International Headache Society, which were met in these three cases. CONCLUSIONS:
      Trigeminal neuralgia is a rare cause of postoperative ophthalmic pain and is a
      challenging diagnosis for the ophthalmologist. It is necessary to consider the
      differential diagnosis of atypical pain after ophthalmic surgery.

PMID- 30193590
TI  - Pharmacological sympathetic denervation prevents the development of polycystic
      ovarian syndrome in rats injected with estradiol valerate.
AB  - BACKGROUND: The injection of estradiol valerate in female rats induces polycystic
      ovary syndrome, which is characterized by polycystic ovaries, anovulation, and
      hyperandrogenism. These characteristics have been associated with an increase in
      the ovarian concentration of norepinephrine, which occurs before establishing the
      polycystic ovary syndrome. The bilateral section of the superior ovarian nerve
      restores ovarian functions in animals with polycystic ovary syndrome. The
      superior ovarian nerve provides norepinephrine and vasoactive intestinal peptide
      to the ovary. An increase in the activity of both neurotransmitters has been
      associated with the development of polycystic ovary syndrome. The purpose of the
      present study was analyzed the participation of the noradrenergic nervous system
      in the development of polycystic ovary syndrome using guanethidine as a
      pharmacological tool that destroys peripheral noradrenergic nerve fibers.
      METHODS: Fourteen-day old female rats of the CIIZ-V strain were injected with
      estradiol valerate or vehicle solution. Rats were randomly allotted to one of
      three guanethidine treatment groups for denervation: 1) guanethidine treatment at
      age 7 to 27-days, 2) guanethidine treatment at age 14 to 34- days, and 3)
      guanethidine treatment at age 70 to 90- days. All animals were sacrificed when
      presenting vaginal oestrus at age 90 to 94-days. The parameters analyzed were the
      number of ova shed by ovulating animals, the ovulation rate (i.e., the numbers of
      ovulating animals/the numbers of used animals), the serum concentration of
      progesterone, testosterone, oestradiol and the immunoreactivity for tyrosine
      hydroxylase enzyme. All data were analyzed statistically. A p-value of less than
      0.05 was considered significant. RESULTS: Our results show that the elimination
      of noradrenergic fibers before the establishment of polycystic ovary syndrome
      prevents two characteristics of the syndrome, blocking of ovulation and
      hyperandrogenism. We also found that in animals that have already developed
      polycystic ovary syndrome, sympathetic denervation restores ovulatory capacity,
      but it was not as efficient in reducing hyperandrogenism. CONCLUSION: The results
      of the present study suggest that the noradrenergic fibers play a stimulant role
      in the establishment of polycystic ovary syndrome.

PMID- 30193593
TI  - Correction to: Impact assessment of Iran's health technology assessment
      programme.
AB  - It has been highlighted that the original article [1] contains a typesetting
      mistake in affiliation 2.

PMID- 30193594
TI  - [Establishment of An Animal Model of Transfusion-related Acute Lung Injury and
      the Role of Soluble CD40 Ligand in the Development of Transfusion-related Acute
      Lung Injury].
AB  - Objective To establish an animal model of transfusion-related acute lung injury
      (TRALI) and investigate the role of soluble CD40 ligand (sCD40L) in the
      development of TRALI. Methods The TRALI animal model established by trauma
      hemorrhage-transfusion. Lung edema was evaluated by histopathological examination
      and the protein and Evans blue dye accumulation in bronchoalveolar lavage fluid.
      The concentration of sCD40L in storage packed red blood cell (PRBC) and rat's
      plasma was measured by enzyme-linked immunosorbent assay (ELISA). Results There
      were obvious epithelial hyperplasia and inflammatory cell infiltration in the
      lung tissue of 7 d-PRBC-treated group. The accumulation of protein in
      bronchoalveolar lavage fluid of 7 d-PRBC-treated group [(13.17+/-5.76)mg] was
      significantly higher than that in normal controls [(1.21+/-0.66)mg] and normal
      saline (NS)-treated group [(4.94+/-2.15) mg] (F=17.605,P<0.001). The leakage
      amount of Evans blue dye in 7 d-PRBC-treated group [(0.0109+/-0.0067)%/min] was
      significantly higher than that in NS-treated group [(0.0026+/-0.0006) %/min]
      (t=2.998,P=0.03). The concentration of sCD40L of the 7 d PRBC [(451.58+/-73.28)
      pg/ml] was significantly higher than 0 d PRBC [(277.94+/-98.18)pg/ml]
      (t=2.834,P=0.03). The concentration of sCD40L in the plasma of 7 d-PRBC-treated
      group [(878.21+/-125.30)pg/ml] was significantly higher than those in normal
      controls [(289.78+/-62.60)pg/ml] and NS-treated group [(418.07+/-47.68)pg/ml]
      (F=78.715,P<0.001). Conclusion The TRALI animal model was successfully
      established with trauma-hemorrhage-transfusion. The concentration of sCD40L in
      plasma of rats with massive transfusion is remarkably increased,suggesting sCD40L
      may play a role in the development of TRALI.

PMID- 30193595
TI  - [Value of Superb Micro-vascular Imaging in Diagnosing Carotid Artery Vulnerable
      Plaque].
AB  - Objective To explore the diagnostic value of superb micro-vascular imaging (SMI)
      for patients with vulnerable plaque of carotid artery. Methods Totally 69 patient
      with carotid hypoechoic or predominantly hypoechoic plaque (108 plaques),which
      were identified by conventional ultrasound,underwent SMI and contrast-enhanced
      ultrasound (CEUS). Based on the scores of CEUS and SMI (0,1,and 2 points),the
      consistency of SMI and CEUS in detecting plaque neovascularization was assessed.
      Results SMI could more clearly display the profile and morphology of the plaques
      than conventional ultrasound. SMI showed that there were neovascularization in 75
      plaques,and CEUS showed that there were neovascularization in 76 plaques;the
      number of scoring consistency in the plaque neovascularization under SMI and CEUS
      was 90,suggesting these two results were highly consistent (Kappa value=0.748).
      There were 6 ulcerated carotid plaques detected by SMI,and the same 6 ulcerated
      carotid plaques were detected by CEUS,showing complete consistency. Of these 108
      plaques,55 caused stenosis of the lumen,and SMI showed there was no correlation
      between plaque neovascularization and stenosis of the lumen caused by plaques
      (P=0.473). Conclusion SMI can clearly display the morphology and outline of the
      plaques and the plaque neovascularization. Therefore,it can be used for
      evaluating plaque vulnerability.

PMID- 30193592
TI  - Characterization of a Listeria monocytogenes meningitis mouse model.
AB  - BACKGROUND: Listeria monocytogenes is a common cause of bacterial meningitis. We
      developed an animal model of listerial meningitis. METHODS: In survival studies,
      C57BL/6 mice received intracisternal injections with different L. monocytogenes
      sequence type 1 (ST1) colony forming units per milliliter (CFU; n = 48, 105, 106,
      107, 108, and 109 CFU/ml). Second, mice were inoculated with 108 CFU/ml ST1 and
      sacrificed at 6 h and 24 h (n = 12/group). Outcome parameters were clinical
      score, CFUs, cyto- and chemokine levels, and brain histopathology. Third, 84 mice
      were inoculated (109 CFU/ml ST1) to determine optimal antibiotic treatment with
      different doses of amoxicillin and gentamicin. Fourth, mice were inoculated with
      109 CFU/ml ST1, treated with amoxicillin, and sacrificed at 16 h and 24 h (n =
      12/group) for outcome assessment. Finally, time point experiments were repeated
      with ST6 (n = 24/group). RESULTS: Median survival time for inoculation with 108
      and 109 CFU/ml ST1 was 46 h and 40 h; lower doses of bacteria led to minimal
      clinical signs of disease. Brain levels of IL-6, IL-17A, and IFN-gamma were
      elevated at 24 h, and IL-1beta, IL-6, IL-10, IFN-gamma, and TNF-alpha were
      elevated in blood at 6 h and 24 h. Histopathology showed increased meningeal
      infiltration, vascular inflammation of meningeal vessels, hemorrhages, and
      ventriculitis. In the treatment model, brain levels of IL-6 and IL-17A and blood
      levels of IL-6 and IFN-gamma were elevated. Compared to ST6, infection with ST1
      led initially to higher levels of IL-1beta and TNF-alpha in blood and more
      profound neuropathological damage. At 16 h post inoculation, IL-1beta, IL-10, and
      TNF-alpha in blood and IL-6, IL17A, TNF-alpha, and IFN-gamma levels in brain were
      higher in ST1 compared to ST6 without differences in CFUs between STs. At 24 h,
      neuropathology score was higher in ST1 compared to ST6 (p = 0.002) infected mice.
      CONCLUSIONS: We developed and validated a murine model of listerial meningitis.
      ST1-infected mice had a more severe inflammatory response and brain damage as
      compared to ST6-infected mice.

PMID- 30193596
TI  - [Clinical Features of Pneumocystis Jiroveci Pneumonia in Patients with
      Inflammatory Bowel Disease].
AB  - Objective To investigate the clinical features of patients with inflammatory
      bowel disease (IBD) complicated with Pneumocystis Jiroveci Pneumonia (PJP).
      Methods We retrospectively analyzed the clinical data of 5 patients who were
      hospitalized in Peking Union Medical College Hospital from January 2012 to July
      2017 for treatment of IBD complicated with PJP. Demographic
      characteristics,clinical manifestations,treatments,and outcomes were
      descriptively analyzed. Results Of these five patients,four had ulcerative
      colitis (UC) and one had Crohn's disease (CD). All patients were males,with an
      average age of (61.8+/-1.9) years. All patients were in active disease status and
      had symptoms including cough and suffocation. Three patients had hypoxemia,among
      whom two developed type 1 respiratory failure. Three patients were treated with
      immunosuppressive medications (corticosteroids and/or immunosuppressant drugs)
      before the diagnosis of PJP. Lymphocyte counts in three patients were less than
      0.6*109/L. CD4+T cells in two patients were less than 200*106/L. Four patients
      had elevated serum cytomegalovirus DNA. The level of beta-D-glucan was elevated
      in four patients. Chest CT showed bilateral diffuse ground glass opacification.
      PJP-DNA was positive in sputum or bronchoalveolar lavage fluid in all patients.
      Two patients with type 1 respiratory failure required invasive mechanical
      ventilation. All patients received trimethoprim-sulfamethoxazole and
      methylprednisolone treatment. Four patients recovered completely and one died.
      Conclusion Elderly (aged>55 years) IBD patients who are receiving immune
      suppressive therapy or with decreased peripheral blood lymphocyte count are at
      higher risk of PJP.

PMID- 30193597
TI  - [Effect of Compound Medicine of Tanshinone 2A and Resveratrol on Peak Bone Mass
      in Growing Rats].
AB  - Objective To study the effect of the compound medicine of tanshinone 2A and
      resveratrol on peak bone mass in growing rats and to explore its possible
      mechanism,so as to explore anti-osteoporosis mechanisms of new traditional
      Chinese medicine (TCM) drugs. Methods Totally 40 1-month-old female Wistar rats
      were randomly divided into tanshinone 2A group,resveratrol group,compound group
      (tanshinone 2A and resveratrol),and normal control group,with 10 rats in each
      group. Body weight was measured once every two weeks,and the whole body bone
      mineral density was measured with dual-energy X-ray monthly. When the whole-body
      bone mineral density became statistically significant between medication groups
      and control group,all animals were sacrificed to determine the bone mineral
      density of vertebrae and right femoral bone. The biomechanical properties of
      femur and vertebrae were measured by AGS-X series universal test,then the bone
      morphology was analyzed with Fuchsin picric acid staining. Finally,the levels of
      tartrate-resistant acid phosphatase 5b and osteocalcin were measured with enzyme
      linked immunosorbent assay.Results The body weights were not statistically
      significant among all groups (P>0.05). The whole-body bone mineral density showed
      no significant difference (P>0.05) after feeding for 1 month;however,two months
      later,it was significantly different between medication groups and control
      group;in particular,the whole-body (P=0.016),femoral (P=0.001),and vertebral bone
      mineral density (P=0.034),bone trabecular number (P=0.024),thickness
      (P=0.040),and area (P=0.038) were significantly increased in the compound
      group,along with the significantly decreased trabecular separation degree
      (P=0.032). Compared with the control group,the compound group had significantly
      increased osteocalcin (P=0.033) and tartrate-resistant acid phosphatase 5b
      (P=0.028) levels in serum.Conclusion The compound of tanshinone 2 A and
      resveratrol can improve the bone density and bone quality in rats,and such effect
      is higher than either tanshinone 2 A monomer or resveratrolmonomer.

PMID- 30193598
TI  - [Correlation of Matrix Metalloproteinases-9 with Microemboli Shedding in Carotid
      Endarterectomy].
AB  - Objective To investigate the change of serum matrix metalloproteinases-9 (MMP-9)
      expression before,during,and after carotid endarterectomy (CEA) and to
      investigate the prognostic role of MMP-9. Methods Forty carotid stenosis patients
      who underwent CEA in the Department of Vascular Surgery,Peking Union Medical
      College Hospital from February to September 2012 were enrolled in this study.
      Based on the findings of transcranial doppler monitoring,patients were divided
      into embolic-positive group and emboli-negative group. Serum samples were
      obtained from 40 consecutive patients undergoing CEA before operation (pre
      op),before de-clamping,30 minutes after de-clamping,and 12 hours after operation
      (12-h post-op). MMP-9 expression was quantified using enzyme-linked immunosorbent
      assay and gelatin zymography. Student's t-test and chi-square test were used to
      compare the differences between these two groups. Results Of these 40
      patients,microemboli were detected in 8 patients. The 12-h post-op MMP-9 level
      was significantly higher than the pre-op level in the emboli-positive group
      [(904.27+/-369.47)ng/ml vs. (333.88+/-126.32)
      ng/ml,t=4.132,P=0.001].However,there was no difference between pre-op and 12-h
      post-op MMP-9 levels in the emboli-negative group [(375.83+/-194.36) ng/ml vs.
      (472.74+/-271.21) ng/ml,t=-1.643,P=0.081]. Gelatin zymography also showed higher
      MMP-9 activity in the emboli-positive group than in the emboli-negative group.
      Conclusion Serum MMP-9 concentration remarkably increases 12 hours after CEA in
      patients with microemboli shedding,suggesting MMP-9 may be a potential biomarker
      for CEA-related cerebral ischemic injury.

PMID- 30193599
TI  - [Chest CT Findings of Primary Neuroendocrine Tumor of Thymus:Analysis of 7
      Cases].
AB  - Objective To explore the clinical features of primary neuroendocrine tumor of
      thymus (pNET) on computed tomography (CT). <b>Method</b> CT findings and clinical
      features of 7 patients with pathologically confirmed primary pNET were
      retrospectively analyzed. Results There were 2 male and 5 female patients aged
      (52.1+/-13.3) years,without accompanying endocrine symptoms. Three patients had
      low-and intermediate-grade pNET and 4 had high-grade pNET. CT showed solid masses
      in the anterior mediastinum with heterogeneous density,and the average maximum
      diameter was 6.6 cm. Five patients had necrosis and 4 patients had calcification.
      After contrast administration,5 cases showed flower ring-like enhancement and 2
      cases showed rim enhancement. All lesions showed invasive features,including
      vessel encompassment (n=5),involvement of surrounding fat space (n=4),involvement
      of the pleura (n=3),involvement of pericardium (n=2),involvement of chest wall
      (n=1),direct lung involvement (n=2),lymphadenopathy (n=1),and primary renal
      neuroendocrine tumor with lung metastasis (n=1). Conclusion pNET is mainly seen
      in middle-aged people. The typical characteristics of pNET on CT include large
      mass,calcification,necrosis,and flower ring-like enhancement. CT can clearly
      display the pNET and the involvement of its surrounding tissues and therefore is
      helpful for preoperative diagnosis and WHO classification of pNET.

PMID- 30193600
TI  - [Comparisons of Clinical Effectiveness and Survival between Continuous and
      Interrupted Chest Compressions in Out-of-hospital Cardiac Arrest].
AB  - Objective To compare the clinical outcomes of continuous chest compressions (CCP)
      or interrupt chest compression (ICP) for the cardiac arrest patients. Methods
      Totally 114 adult patients with out-of-hospital non-trauma-related cardiac arrest
      that needed cardiopulmonary resuscitation (CPR) in Quzhou People's Hospital from
      January 2014 to January 2017 were enrolled in this study. Patients who divided
      into CCP group (n=70) and ICP group (n=44) according to the maneuvers. The
      clinical data of these two groups were collected and compared. Results The chest
      compression fraction was higher in CCP group than in ICP group (0.85+/-0.05 vs.
      0.75+/-0.06,t=9.868,P=0.000),and the rate of chest-compression pause per minute
      was significantly lower in CCP group (3.5+/-1.6 vs. 6.9+/-3.8,t=-10.669,P=0.000).
      The interval from arrival at a first aid location to CPR,duration of CPR,electric
      defibrillation frequency,airway establishment,intubation time,and use of first
      aid drugs were not statistically significant (all P>0.05). Significantly lower
      proportion of patients in CCP group were transported to a hospital (42.8% vs.
      56.8%,Chi2=0.198,P=0.032). The proportion of patients achieving recovery of
      spontaneous circulation (ROSC) in CCP group were significantly lower than in ICP
      group (28.5% vs.47.7%,Chi2=0.191,P=0.038). The proportion of patients who got
      successful resuscitation in CCP group was significantly lower than in ICP group
      (20.0% vs. 38.6%,Chi2=4.470,P=0.029). The proportion of patients who survived and
      were discharged was significantly lower in CCP group than in ICP group (8.6%
      vs.22.7%,Chi2=0.487,P=0.041). There was no significant difference between these
      two groups in ROSC time,proportion of survivors one month after
      discharge,proportion of survivors six months after discharges,and neurological
      outcomes (all P>0.05). Among the survivors,2 patients had ST-elevation myocardial
      infarction,1 had rheumatic heart disease,2 had non-ST segment elevations
      myocardial infarction,and 1 had dilated cardiomyopathy. Multivariate Cox
      proportional hazard regression analysis was used to analyze the independent
      factor of prognosis. The time from cardiac arrest to CPR (HR=1.047,95% CI=1.003
      1.093,P=0.034),the time from CPR to ROSC (HR=1.021,95% CI=1.003
      1.038,P=0.020),and Glasgow Coma Scale (GCS) 1 score (HR=1.551,95% CI=1.022
      2.355,P=0.039) were the independent risk factor for deaths within 180 days after
      discharge. Conclusion Long interval from cardiac arrest to CPR,long interval from
      CPR to ROSC,and a Glasgow Coma Scale score of>1 are the independent risk factors
      of deaths within 180 days after discharge. Therefore,the survival outcomes of CCP
      may not be superior to ICP in patients with out-of-hospital cardiac arrest.

PMID- 30193601
TI  - [Value of Monochromatic Imaging on Spectral Detector CT in Metal Artifact
      Reduction of Denture Implants].
AB  - Objective To evaluate the role of monochromatic imaging in reducing metal
      artifacts and improving image quality in patients with denture implants
      undergoing head/neck plain CT. Methods Forty patients with denture implants
      undergoing head/neck plain CT on a dual-layer spectral detector CT were enrolled.
      The conventional and monochromatic 110 keV images were reconstructed from the
      same acquisition. The regions of interests (ROIs) were placed on the artifact
      streak (CT1),the soft tissue affected by the artifact (CT2),and the unaffected
      tissue (CT3). The artifact index (AI) and standard deviation (SD) were
      calculated. The image quality was compared.Results The attenuation of CT1 was
      significantly improved on monochromatic images than on conventional images [
      195.00 (-700.40,44.80) vs. -336.50 (-1024.00,-77.00),P=0.00]. The attenuation of
      CT2 was significant different between monochromatic and conventional images
      [46.10 (-0.20,91.60) vs. 102.80 (4.60,210.20),P=0.00]. The difference between CT2
      and CT3 was significantly smaller on monochromatic images than on conventional
      images [14.55 (0.00,44.00) vs. 51.30 (0.30,168.30),P=0.00]. The SD of CT2 was
      significantly smaller on monochromatic images than on conventional images [14.75
      (7.80,35.00) vs. 23.25 (7.60,56.00),P=0.00]. The AI was significantly improved by
      monochromatic imaging [12.76 (3.53,34.14) vs. 19.00 (2.43,54.32),P=0.00].
      Conclusion The monochromatic imaging can effectively reduce the artifacts caused
      by denture implants and improve image quality on head/neck plain CT.

PMID- 30193602
TI  - [Correlation of Heart Rate and Geographical Environmental Factors with Reference
      Values of Left Ventricular Ejection Fraction in Healthy Adult Males].
AB  - Objective To establish a model for obtaining the reference values of left
      ventricular ejection fraction(LVEF) in Chinese healthy adult males by exploring
      the relationships of these reference values with heart rate and geographical
      environment factors. Methods LVEF and heart rate reference values (X1) were
      collected from 3502 healthy adult males from 2006 to 2016. Correlation analysis
      and ridge regression were employed to extract dependent geographical environment
      factors and predict the LVEF reference values. The Kriging interpolation was
      applied to reveal the spatial distribution of the LVEF reference values. Results
      LVEF and heart rate (X1) were significantly correlated with five geographical
      environment factors. LVEF was negatively correlated with heart rate (X1),latitude
      (X3),and annual range of temperature (X9) and positively correlated with annual
      mean air temperature (X6),annual mean relative humidity (X7),and annual
      precipitation amount (X8). The reference values of LVEF had a negative
      correlation with heart rate. The ridge regression equation of LVEF reference
      values and geographical environment factors was as follows:Y=68.464-0.0949X3
      0.0619X6-0.00128X7+0.00069X8-0.0199X9+/-3.329. The equation of LVEF reference
      values with heart rate and geographical environment factors was Y=75.923-0.1035X1
      0.0958X3-0.0741X6+0.00094X7+0.00081X8-0.0211X9+/-3.288. Conclusion The LVEF
      reference values among Chinese healthy adult males decreased from south to north.
      They can be determined based on the regression models after the geographical
      factors of a certain region are obtained. The new model offers a geographic basis
      for the establishment of LVEF reference values.

PMID- 30193603
TI  - [Relationship between Angiotensin Converting Enzyme Gene Polymorphism and Carotid
      Atherosclerotic Plaque: A Study Based on Vessel Wall Magnetic Resonance Imaging].
AB  - Objective To investigate the relationship between angiotensin converting
      enzyme(ACE) gene polymorphism and carotid plaque composition,vessel wall
      morphology,and clinical symptoms based on vessel wall magnetic resonance imaging.
      Methods Totally 75 hypertensive patients(75 internal carotid artery plaques) with
      maximum plaque thickness>=1.5 mm,according to the ACE insertion(I) or deletion(D)
      gene polymorphism,were divided into ACE 2 genotype group(n=37) and ACE ID/DD
      genotype group(n=38). The influences of plaque composition,vessel wall
      morphology,clinical symptoms,and use of ACE inhibitor or angiotensin receptor
      blocker(ACEI/ARB) on vessel wall morphology were analyzed. Results Compared with
      ACE 2 genotype group,the ACE ID/DD genotype group had significantly higher
      incidence of ischemic stroke(Chi2=3.921,P=0.048). The plaque composition and
      vessel wall morphology showed no significant difference between these two groups.
      Inside ACE ID/DD genotype group,the carotid remodeling index was significantly
      lower in users of ACEI/ARB than non-users of ACEI/ARB(1.85+/-0.60 vs. 2.48+/
      0.40;t=3.854,P=0.001).Conclusion In primary hypertension,ACE ID/DD genotype may
      be associated with carotid atherosclerotic plaque.

PMID- 30193604
TI  - [Magnetic Resonance Imaging Features and Their Pathological Mechanisms of
      Hashimoto's Encephalopathy].
AB  - Objective To analyze the routine and functional magnetic resonance imaging(MRI)
      features and their potential pathological mechanisms of Hashimoto's
      encephalopathy(HE). Methods The clinical data and routine and functional MRI
      images of 30 HE patients who were treated in our center from January 2010 to
      April 2017 were retrospectively reviewed. Among them,15 patients were examined
      with contrast-enhanced MRI,16 with diffusion-weighed imaging(DWI),8 with magnetic
      resonance angiography,2 with magnetic resonance spectroscopy,and 1 with both
      arterial spin labeled perfusion imaging and diffusion tensor imaging. Seven
      patients had consecutive clinical and imaging data. The distribution,MRI
      signals,and functional MRI features of HE were analyzed. Results Among 30 HE
      patients,routine MRI showed negative results in 8 cases and abnormal findings in
      22 cases. Among 22 abnormal cases,9 were characterized by small cerebral vascular
      disease and 13 had non-specific abnormalities;of these 13 cases,12 had lesions
      mainly located at the supratentorial white matter,11 had multiple lesions,and 2
      had lesions complicated with cerebellum atrophy. The lesions were focal or
      confluent,punctate or small patchy,showing abnormal signal intensity with iso-or
      hypo-intensity on T1-weighed imaging,hyper-intensity on both T2-weighed imaging
      and fluid-attenuated inversion recovery. Most of the lesions had no
      enhancement(12/15). Among 7 cases with abnormalities on DWI,hyper-intensity on
      DWI and hypo-intensity on apparent diffusion coefficient were seen in 3 sudden
      acute cases and hyper-intensity on DWI and increased apparent diffusion
      coefficient value in 4 sub-acute or slow onset cases. Three cases showed
      localized intracranial artery stenosis. In 2 cases,magnetic resonance
      spectroscopy revealed significant lower N-acetylaspartate peak,higher choline
      peak,and visible lactate peak or lipid peak. Of 7 cases with follow-up data,3
      cases had no change,4 cases had changes including softening lesions(2/4),remitted
      and relapsed lesions(1/4),and rapid progression of brain atrophy with negative
      finding on the initial MRI(1/4). Conclusion Routine MRI combined with functional
      imaging can show the features of HE from different perspectives. Routine MRI
      shows multifocal or confluent lesions in the white matter,mostly without
      enhancement,while functional imaging may reveal pathological characteristics of
      different phases of acute or chronic ischemia and demyelinating changes of HE.
      Combined with clinical data,MRI can differentiate HE from other diseases based on
      routine and functional MRI appearances.

PMID- 30193605
TI  - [Associations of the MicroRNA-143/145 Polymorphisms with Cardiovascular Risk
      Factors and the Severity of Coronary Heart Disease].
AB  - Objective To explore the possible effects of the microRNA(miR)-143/145
      polymorphisms on cardiovascular risk factors and the severity of coronary heart
      disease(CHD) in Chinese Han people. Methods Polymerase chain reaction-restriction
      fragment length polymorphism analysis was employed to identify the genotypes of
      the rs353292 and rs4705343 polymorphisms for 380 patients with CHD and 163 CHD
      free controls. The physiological and biochemical parameters between the genotypes
      were compared in the CHD patients and in controls,and the incidence of myocardial
      infarction(MI) was also compared between the genotypes in the CHD patients.
      Results The subjects with the rs353292 TT genotype had higher serum levels of
      triglycerides(F=3.00,P=0.05) and glucose(F=9.91,P<0.001) than the C carriers,and
      the subjects with the rs4705343 TT genotype had significantly higher prevalence
      of hypertension(Chi2=6.35,P=0.04) than the C carriers in the control group. The
      patients with the rs353292 TT genotype had significantly higher serum levels of
      hypersensitive C-reactive protein(hs-CRP)(F=8.43,P<0.001) than the C carriers in
      the CHD group,and the frequency of MI was significantly higher in the patients
      with the rs353292 TT genotype than that in the C carrier
      patients(Chi2=5.29,P=0.02). Conclusion The T allele of the rs353292 polymorphism
      is associated with serum hs-CRP levels in CHD patients,and it may affect the
      occurrence and development of MI by up-regulation of CRP gene through miR
      143/145. The rs4705343 polymorphism is not related to the risk and severity of
      CHD.

PMID- 30193606
TI  - [Diffusion Tensor Imaging in Early Diagnosis and Prognostic Prediction of
      Intervertebral Disc Change in Patients with Brucella Spondylitis].
AB  - Objective To explore the value of fractional anisotropy(FA) and apparent
      diffusion coefficient(ADC) in the early diagnosis of intervertebral disc change
      in patients with Brucella spondylitis(BS) and in the assessment of BS disc
      changes after treatment and to further investigate the imaging features of BS in
      its acute,subacute,and chronic stages. Methods Totally 60 serologically or
      pathologically confirmed BS patients who were treated in the First Hospital
      Affiliated to Hebei North University(n=20) or ZhangJiakou Infectious Diseases
      Hospital(n=40) were enrolled. BS patients were scanned by CT,magnetic resonance
      imaging,and diffusion tensor imaging,and the FA and ADC values of the disc were
      measured using the DTI Fiber Trak package. The FA and ADC values were compared in
      each period and after treatment. Results The ADC value significantly increased
      and the FA value significantly decreased in different stages(P<0.01). Six months
      after treatment,the ADC value was significantly lower than the pre-treatment,and
      the FA value was significantly increased(P<0.01). The ADC value 12 months after
      treatment for patients in acute or subacute stage and the FA value 12 months
      after treatment for patients in all stages were significantly different from
      those in the 6th month after treatment(P<0.01),and the only exception was that
      the ADC value in the chronic stage was not significantly different between 12th
      and 6th month after treatment(P=0.089).Conclusion FA and ADC values are more
      sensitive than conventional MRI sequences in the diagnosis of BS intervertebral
      disc change and therefore can be used for the early diagnosis and prognostic
      prediction.

PMID- 30193607
TI  - [Effect of MicroRNA-199 on Proliferation and Migration of Gastric Carcinoma
      Cells].
AB  - Objective To detect the expression of microRNA(miR)-199 in gastric carcinoma
      tissues and cell lines, and further explore the effect and molecular mechanism of
      miR-199 on the proliferation and migration of gastric carcinoma cell lines.
      Methods Reverse transcriptase-polymerse chain reaction was used to detect the
      expression of miR-199 in gastric carcinoma and adjacent normal tissue obtained
      from 51 patients and in gastric carcinoma cell lines and human gastric epithelial
      cell line GES-1. The gastric carcinoma cell lines over-expressing and low
      expressing miR-199 were established to detect their proliferation and migration
      abilities. Dual-luciferase reporter assay was performed to detect the regulatory
      effect of miR-199 on the 3'untranslated region of TBL1XR1. Western blot was used
      to explore the miR-199-related mechanism. Results The relative expression of miR
      199 in gastric carcinoma tissues was significantly lower than that in the
      adjacent normal tissue (0.2635+/-0.0303 vs. 1.6700+/-0.9613, t=13.95, P<0.001).
      The relative expressions of miR-199 in gastric carcinoma cell lines AGS (0.81,
      t=9.13, P<0.001), SGC-7901 (0.83, t=8.88, P<0.001), MKN28 (0.58, t=10.80,
      P<0.001), KATO-3 (0.60, t=10.31, P<0.001), MKN-45 (0.27, t=13.10, P<0.001) were
      significantly lower than that in the normal gastric cell line GES-1 (2.1). In miR
      199 over-expressed cell lines, the cell proliferation and migration significantly
      decreased as compared with the control group of gastric carcinoma cells (731+/-13
      vs. 345+/-18, t=24.90, P<0.001), and in miR-199 low-expressed group, the cell
      proliferation and migration increased compared with the control group of gastric
      carcinoma cells (257+/-16 vs. 657+/-8, t=32.59, P<0.001). Dual-luciferase
      reporter assay proved that miR-199 directly targeted on the 3' untranslated
      region of TBL1XR1. Western blot analysis showed that miR-199 inhibited the
      expression of TBL1XR1. Conclusion The over-expression of miR-199 in gastric
      carcinoma is associated with the decreased ability of proliferation and migration
      of gastric carcinoma cells by targeting TBL1XR1.

PMID- 30193608
TI  - [Values of Different Laboratory Diagnostic Approaches for Tuberculous
      Peritonitis].
AB  - Objective To evaluate the diagnostic accuracy of different laboratory approaches
      for tuberculous peritonitis(TP).Methods The clinical data of patients with
      suspected TP who were mainly manifested as ascites in Peking Union Medical
      College Hospital from January 2014 to June 2017 were retrospectively analyzed.
      Ascites samples were tested with different diagnostic approaches,including acid
      fast stain,culture for mycobacterium,real-time polymerase chain reaction for
      identifying DNA of mycobacterium tuberculosis,and T-cell spot of tuberculosis
      test(T-SPOT.TB). Results Totally 163 cases aged 15-84 years [mean+/-SD:(50+/
      17)years] with complete data were enrolled,among whom 82(50.3%) were males and
      81(49.7%) were females. Finally,27 patients were confirmed as TP,which was
      excluded in the other 136 cases. The sensitivity and specificity of ascites acid
      fast stain were 0% and 100%,respectively,followed by ascites culture for
      mycobacterium(21.74% and 100%),real-time polymerase chain reaction for DNA of
      mycobacterium tuberculosis in ascites(18.52% and 100%),T-SPOT.TB on
      ascites(95.42% and 61.90%),and T-SPOT.TB on peripheral blood(76.19% and 80.18%).
      Conclusion The diagnosis of tuberculous peritonitis remains challenging because
      of the limitations of the currently available diagnostic tests. Diagnosis should
      also be based on clinical manifestations and auxiliary examinations.

PMID- 30193609
TI  - [Correlation between Ameliorated Kawashima Itch Scale and Visual Analogue Scale].
AB  - Objective To preliminarily validate the clinical usability of the ameliorated
      Kawashima Itch Scale(Xie-Kawashima Itch Scale) among adult pruritic patients on
      maintenance hemodialysis. Methods Xie-Kawashima Itch Scale was developed on the
      basis of Kawashima Itch Scale. Patients were asked to record their pruritus
      condition according to Xie-Kawashima Itch Scale or visual analogue scale(VAS)
      during daytime and night for two weeks. The record at the second week was used
      for analyzing the correlation between Xie-Kawashima Itch Scale and VAS. Results
      Totally 134 patients were enrolled in this study,among whom 128 entered the final
      analysis. Xie-Kawashima Itch Scale was positively correlated with
      VAS(rs=0.832,95% CI=0.810-0.851,P<0.01 for daytime record;and rs=0.848,95%
      CI=0.828-0.865,P<0.01 for night record). Subgroup analysis also showed similar
      correlations between different age groups and among different gender groups.
      Conclusion Xie-Kawashima Itch Scale has good correlation with VAS in patients on
      hemodialysis,without being affected by age or gender. Thus,it can be a useful
      tool for the assessment of pruritus in clinical practice and research.

PMID- 30193610
TI  - [Research Advances in Insomnia Disorder Based on Magnetic Resonance Imaging].
AB  - As the most common sleep disorder,insomnia decreases the quality of life and is
      the high risk for cardiovascular disease,neurological disease,and psychiatric
      disease. It has become a major public health problem. In recent years,magnetic
      resonance imaging technology has been widely used for research on the brain
      structure in patients with insomnia. This article summarizes recent research
      findings of the abnormal brain structure and the potential neural mechanism of
      insomnia,with an attempt to understand the mechanisms in abnormal brain regions
      and thus further identify the pathophysiology of insomnia.

PMID- 30193611
TI  - [Pathogenic Mechanisms of the Focal Segmental Glomerulosclerosis and Its Role in
      the Progression of IgA Nephropathy].
AB  - Focal segmental glomerulosclerosis (FSGS),a common pathological change in kidney
      diseases,may be caused by primary factors or multiple secondary factors. Its
      pathogenic mechanism remains a hot topic in kidney disease research. FSGS-like
      pathologic changes are highly in IgA nephropathy. It has been speculated that
      FSGS in IgA nephropathy might be caused by hemodynamics changes,and podocyte
      injury,which,however,have not been well documented. Our current review focuses on
      the pathogenesis of secondary FSGS and its role in the progression of IgA
      nephropathy,with an attempt to provide more insights in the treatment of IgA
      nephropathy.

PMID- 30193612
TI  - [Psoriasis,Cardiovascular Disease,and Adipokines].
AB  - Psoriasis usually combines with metabolic diseases,and the prevalence of
      cardiovascular disease remarkably increases in psoriatic patients.
      Adipokines,which play an important role in the cardiovascular diseases,also
      express abnormally in psoriasis and may induce or exacerbate the skin lesion. The
      adipokines associated with psoriasis and cardiovascular disease include
      adiponectin,leptin,resistin,omentin,visfatin,chemerin,and retinoid binding
      protein 4 (RBP-4). The levels of adiponectin and omentin apparently decrease in
      psoriatic patients compared to healthy controls,and thus they may play protective
      roles for psoriasis. Similarly,adiponectin plays a protective role in
      cardiovascular disease,but the role of retina in cardiovascular disease is still
      controversial. However,the concentrations of
      leptin,resistin,visfatin,chemerin,and RBP-4 in patients with psoriasis or
      cardiovascular disease are significantly higher than those of the
      controls;therefore,they may serve as the pathogenic factors for both diseases.
      Low adiponectin,leptin,visfatin,and chemerin levels may induce or aggravate
      psoriasis by activating plasmacytoid dendritic cells or T cells,as demonstrated
      in in vitro experiments. However,in vitro experiments also have shown that
      visfatin may inhibit cardiomyocyte apoptosis.

PMID- 30193613
TI  - [Application of Digestive Endoscopy in Diagnosis of Helicobacter Pylori
      Infection].
AB  - Helicobacter pylori (Hp),a proven pathogen of digestive disease,is closely
      associated with gastrointestinal diseases including peptic ulcer,chronic active
      gastritis,stomach cancer,and stomach-associated lymphoid tissue lymphoma.
      Thus,precise and timely diagnosis of Hp is of great significance. In addition to
      13C or 14C breath test,rapid urease test,and other commonly used Hp diagnosis
      methods,some new endoscopic techniques such as magnifying endoscopy,narrow-band
      imaging,confocal laser endomicroscopy,Fuji intelligent chromoendoscopy,and I
      scanning have been used for the direct observation of the fine-structure of
      stomach with Hp infection or for the identification of living Hp. This article
      reviews the application of digestive endoscopy in the diagnosis of Hp infection.

PMID- 30193614
TI  - [Relationship between Autophagy and Curcumin-induced Anticancer Effect].
AB  - Curcumin is a polyphenol extracted from turmeric rhizome and has multiple
      pharmacological roles. Recently,its anticancer properties have been recognized.
      Also,curcumin regulates autophagy in tumor cells via signaling pathways including
      AMP-activated protein kinase,mammalian target of rapamycin,transcription factor
      EB,Beclin-1,B-cell lymphoma 2,and endoplasmic reticulum stress. Considering the
      complicated crosstalk between autophagy and apoptosis,in this article we summaize
      the mechanism of curcumin-induced autophagy and its effect on apoptosis,with an
      attempt to provide insights on tumor therapy.

PMID- 30193615
TI  - [Diagnostric Value of Contrast-enhanced T2 Fluid-attenuated Inversion Recovery
      Imaging for Splenic Hemangioma:A Case Report].
AB  - The diagnostic criteria of splenic hemangioma is the delayed filling enhancement
      pattern on the dynamic contrast CT imaging or magnetic resonance (MR) T1-weighted
      image,which requires long examination time and thus decreases the MR scanning
      efficiency. Contrast-enhanced T2 fluid-attenuated inversion recovery (FLAIR)
      imaging is a new MR imaging technique that can be used to evaluate the intrinsic
      characteristics of hemangioma. However,few literature has discribed its role in
      diagnosing splenic hemangioma. In this article we reported one case of splenic
      hemangioma diagnosed by contrast-enhanced T2 FLAIR imaging,which reduced the MR
      scanning time and provided valuable experience for the diagnosis of splenic
      hemangioma.

PMID- 30193616
TI  - Gorlin Syndrome Presentation and the Importance of Differential Diagnosis of Skin
      Cancer: A Case Report.
AB  - In a busy community practice, clinical skin findings can often be misinterpreted.
      Skin cancers can sometimes mimic rashes like psoriasis, eczema or prurigo
      nodularis in both appearance and symptoms. Gorlin syndrome is one such genetic
      syndrome, characterized by the eruption of multiple and early onset basal cell
      carcinomas (BCCs), which can be mistaken for a rash. We describe a 68-year-old
      female who presented to the dermatology office with a previous history of over 30
      BCCs that had been previously biopsied and/or surgically removed. However, the
      patient had been lost to follow up for several years and had not been seen by a
      skin specialist. In the interim, she had been misdiagnosed as having eczematous
      or psoriatic lesions by primary care providers. Patients with Gorlin syndrome are
      even harder to diagnose as their skin cancers often do not possess the classic
      features associated with a basal cell or squamous cell carcinoma. When in doubt,
      and especially if failing topical therapy, patients presenting with
      dermatological lesions should be properly referred to a specialist for further
      assessment and workup.

PMID- 30193617
TI  - The Myth of Women's Choices in U.S. Maternity Care, Part 2.

PMID- 30193618
TI  - Perceptions of Safety Improvement Among Clinicians Before and After Participation
      in a Multistate Postpartum Hemorrhage Project.
AB  - OBJECTIVE: To measure whether implementation of a comprehensive, 18-month,
      multihospital, multiregion postpartum hemorrhage (PPH) project influenced
      intrapartum clinicians' perceptions of patient safety. DESIGN: Pre- and post
      survey design. SETTING: Survey results from eight hospitals in Georgia, New
      Jersey, and Washington that participated in the Association of Women's Health,
      Obstetric and Neonatal Nurses (AWHONN) PPH Project were included in the final
      analysis. The number of annual births at the hospitals ranged from 1,290 to
      3,567. PARTICIPANTS: There were 473 respondents for the pre-implementation
      survey: 50.5% (239) were registered nurses, 27.1% (128) were physicians, and
      22.4% (106) were other intrapartum clinicians. The post-implementation survey
      included 426 respondents: 62.9% (268) registered nurses, 18.5% (79) physicians,
      and 18.6% (79) other intrapartum clinicians. INTERVENTION/MEASUREMENTS: A paired
      t test was used to compare Safety Attitudes Questionnaire (SAQ) domain scores.
      Pearson's chi-square test was used to analyze perceptions before and after the
      intervention. RESULTS: Baseline SAQ scores were high in all six domains.
      Improvements were noted in five of the six domains measured; none reached
      statistical significance. A significant improvement was found in reported
      perception of the quality of nursing care after implementation of the PPH
      Project. CONCLUSION: SAQ scores remained high and showed some improvement among
      participating hospitals. Participation in the PPH Project increased overall
      perceptions of safety among the clinicians at these hospitals.

PMID- 30193619
TI  - Marijuana Use During Pregnancy.

PMID- 30193620
TI  - Women's Cardiovascular Health.

PMID- 30193621
TI  - Erratum.

PMID- 30193622
TI  - Portable analytical platforms for forensic chemistry: A review.
AB  - This current review article focuses on recent contributions to on-site forensic
      investigations. Portable and potentially portable methods are presented and
      critically discussed about (bio)chemical trace analysis and studies performed
      outside the controlled laboratory environment to rapidly help in crime scene
      inquiries or forensic intelligence purposes. A wide range of approaches including
      electrochemical sensors, microchip electrophoresis, ambient ionization on
      portable mass spectrometers, handheld Raman and NIR instruments as well as and
      point-of-need devices, like paper-based platforms, for in-field analysis of
      latent evidences, controlled substances, drug screening, hazards, and others to
      assist in law enforcements and solving crime more efficiently are highlighted.
      The covered examples have successfully demonstrated the huge potential of
      portable devices for on-site applications. Future investigations should consider
      analytical validation to compete equality and even replace current gold standard
      methods.

PMID- 30193623
TI  - Infrared laser ablation sampling coupled with data independent high resolution
      UPLC-IM-MS/MS for tissue analysis.
AB  - Infrared laser ablation microsampling was used with data-dependent acquisition
      (DDA) and ion mobility-enhanced data-independent acquisition (HDMSE) for mass
      spectrometry based bottom-up proteomics analysis of rat brain tissue. Results
      from HDMSE and DDA analyses of the 12 laser ablation sampled tissue sections
      showed that HDMSE consistently identified approximately seven times more peptides
      and four times more proteins than DDA. To evaluate the impact of ultra
      performance liquid chromatography (UPLC) peak congestion on HDMSE and DDA
      analysis, whole tissue digests from rat brain were analyzed at six different UPLC
      separation times. Analogous to results from laser ablated samples, HDMSE analyses
      of whole tissue digests yielded about four times more proteins identified than
      DDA for all six UPLC separation times.

PMID- 30193625
TI  - Development of a near-infrared fluorescent sensor with a large Stokes shift for
      sensing pyrophosphate in living cells and animals.
AB  - The detection of pyrophosphate (PPi) in living systems has attracted considerable
      attention in recent years due to its biological significance. While many
      fluorescent PPi sensors were developed with emission changes in the visible
      region, near-infrared (NIR) fluorescent sensors for PPi are rather scarce. In
      this paper, a dicyanomethylene-benzopyran (DCMB) based phenol-bridged dinuclear
      Zn(II)-DPA (DPA: dipicolylamine) complex was prepared, which was found to be a
      promising NIR fluorescent sensor for PPi. This sensor features a remarkable large
      Stokes shift (>150 nm) and shows colorimetric and NIR fluorescence changes for
      PPi with high selectivity and sensitivity in 100% aqueous solution. The detection
      limit of this sensor for PPi was determined to be as low as 42 nM. In addition,
      this sensor exhibits low cytotoxicity and can be conveniently employed for
      bioimaging PPi in living cells and animals, indicating it has great potential for
      in vitro and in vivo detection of PPi.

PMID- 30193624
TI  - A novel malic acid-enhanced method for the analysis of 5-methyl-2'-deoxycytidine,
      5-hydroxymethyl-2'-deoxycytidine, 5-methylcytidine and 5-hydroxymethylcytidine in
      human urine using hydrophilic interaction liquid chromatography-tandem mass
      spectrometry.
AB  - 5-Methyl-2'-deoxycytidine (5-mdC), 5-hydroxymethyl-2'-deoxycytidine (5-hmdC), 5
      methylcytidine (5-mrC) and 5-hydroxymethylcytidine (5-hmrC) are epigenetic marks
      of DNA and RNA, and aberrant levels of these modified nucleosides were found to
      be associated with various cancers. Urine is a preferred source of biological
      fluid for biomarker discovery because the sample collection process is not
      invasive to patients. Herein, we developed a novel malic acid-enhanced
      hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC
      MS/MS) method for sensitive and simultaneous quantification of the modified
      cytosine nucleosides in human urine. Malic acid markedly increased the detection
      sensitivities of all four cytosine nucleosides, with the limits of detection
      (LODs) for 5-mdC, 5-hmdC, 5-mrC and 5-hmrC being 0.025, 0.025, 0.025 and 0.050
      fmol, respectively. By using this method, we demonstrated, for the first time,
      the presence of 5-hmrC in human urine, and we successfully quantified 5-mdC, 5
      hmdC, 5-mrC and 5-hmrC in urine samples collected from 90 patients with
      colorectal cancer (CRC) and 90 healthy controls. We found that the levels of 5
      mdC, 5-hmdC, 5-mrC and 5-hmrC in urine were all substantially decreased in CRC
      patients, suggesting that these modified nucleosides might have great potential
      to be noninvasive biomarkers for early detection and prognosis of CRC. Together,
      we established a novel and sensitive method for detecting 5-methylated and 5
      hydroxymethylated cytosine nucleosides in human urine and the results from this
      study may stimulate future investigations about the regulatory roles of these
      cytosine derivatives in the initiation and development of CRC.

PMID- 30193626
TI  - Combined optical and electronic paper-nose for detection of volatile gases.
AB  - In this work, a paper-based optoelectronic sensor (paper-nose) is presented for
      sensing volatile gases in air. The proposed optoelectronic sensor is a
      combination of both colorimetric (optical) and chemiresistive (electronic) sensor
      arrays in order to improve the selectivity of the paper-nose in the complex air
      background. The optical sensors are based on chemoresponsive dyes, namely
      Reichardt's dye (2,6-diphenyl-4-(2,4,6-triphenyl-1-pyridinio)phenolate),
      bromocresol purple, methyl red, bromothymol blue, brilliant yellow and manganese
      tetraphenylporphyrin (Mn-TPP). The chemiresistive sensors are based on
      nanomaterials, such as carbon nanotubes (CNT), PEDOT:PSS, graphite, and an ionic
      liquid, 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide (EMI TFSI).
      Sensor is fabricated through direct handwriting of sensing materials using a pen
      on paper without the need of expensive cleanroom facilities. The optoelectronic
      sensor is tested in ambient air with different volatile gases such as methanol,
      ammonia, toluene, acetone and ethanol and their mixtures of varying
      concentrations. The detected electrical and optical responses together form a
      unique signature for each volatile gas and its mixture. Support-vector machine
      (SVM) is applied for target classification and detection. From the SVM result, it
      is found that better discriminative power is achieved by combining optical and
      electrical responses.

PMID- 30193627
TI  - Electrochemical biosensor made with tyrosinase immobilized in a matrix of
      nanodiamonds and potato starch for detecting phenolic compounds.
AB  - The envisaged ubiquitous sensing and biosensing for varied applications has
      motivated materials development toward low cost, biocompatible platforms. In this
      paper, we demonstrate that carbon nanodiamonds (NDs) can be combined with potato
      starch (PS) and be deposited on a glassy carbon electrode (GCE) in the form of a
      homogeneous, rough film, with electroanalytical performance tuned by varying the
      relative ND-PS concentration. As a proof of concept, the ND/PS film served as
      matrix to immobilize tyrosinase (Tyr) and the resulting Tyr-ND-PS/GCE biosensor
      was suitable to detect catechol using differential pulse voltammetry with
      detection limit of 3.9 * 10-7 mol L-1 in the range between 5.0 * 10-6 and 7.4 *
      10-4 mol L-1. Catechol could also be detected in river and tap water samples.
      This high sensitivity, competitive with biosensors made with more sophisticated
      procedures and materials in the literature, is attributed to the large surface
      area and conductivity imparted by the small NDs (<5 nm). In addition, the ND-PS
      matrix may have its use extended to immobilize other enzymes and biomolecules,
      thus representing a potential biocompatible platform for ubiquitous biosensing.

PMID- 30193628
TI  - Facile synthesis of carbon nanodots with surface state-modulated fluorescence for
      highly sensitive and real-time detection of water in organic solvents.
AB  - In our study, the carbon nanodots (CDs) were synthesized by one-step solvothermal
      method using resorcinol as the only presusor. The obtained CDs contained abundant
      unsaturated oxygen-containing groups resulting from the surface oxidation. A
      novel, simple, and real-time fluorescent assay for the detection of water in
      various organic solvents was thus established by reducing the surface oxidation
      states. Excellent reversibility can be readily achieved by the external stimulus
      water and N,N'-dicyclohexylcarbodiimide (DCC). The water-induced sensitive (limit
      of detection = 0.006%, v/v, in ethanol) and ultrafast (<1 s) response in emission
      properties was capable of water determination in spirit samples in both solution
      and solid-state paper test strips.

PMID- 30193629
TI  - Identification of aminoglycoside antibiotics in milk matrix with a colorimetric
      sensor array and pattern recognition methods.
AB  - Aminoglycoside antibiotics (AAs) abused in animal husbandry can cause antibiotic
      residues in animal-derived foods, which do harm to human beings' health.
      Therefore the detection of AAs residues in the animal-origin foods, such as milk,
      eggs and meat is necessary. We used two single-stranded DNA (ssDNA)
      oligonucleotides as nonspecific receptors to develop a simple colorimetric sensor
      array based on gold nanoparticles (AuNPs) for identification and quantification
      the AAs. Different AA addition triggered the DNA detaching from AuNPs then
      resulted in different degree salt induced aggregation of AuNPs. The aggregation
      induced spectral changes of AuNPs with five AA addition were analyzed based on
      pattern recognition techniques, fisher linear discriminant analysis (FLD) and
      hierarchical cluster analysis (HCA). The results indicated that colorimetric
      sensor array has successfully identified five AAs at a concentration range of 120
      280 nM. Five AAs in aqueous solution and complex milk matrix can be identified
      with an accuracy of 100%. More importantly, our developed sensor array is
      sufficiently sensitive for the discrimination of pure streptomycin (STR), binary
      mixtures of STR and gentamicin (GEN) at a total concentration of 120 nM.

PMID- 30193630
TI  - Ultrasensitive quantitative detection of small molecules with rapid lateral-flow
      assay based on high-affinity bifunctional ligand and magnetic nanolabels.
AB  - An ultrasensitive lateral-flow assay is developed for rapid quantitative
      detection of small molecules on-site. The conceptual novelty, which transfers
      lateral-flow assays to the category of highly sensitive quantitative systems, is
      due to employment of a bifunctional ligand combined with volumetric registration
      of magnetic nanolabels. The ligand provides extremely high affinity for trapping
      the nanolabels and, simultaneously, efficiently competes with the analyzed
      molecules for the limited quantity of antigen-binding sites on the nanolabels.
      The developed assay has been demonstrated as the first express method for
      measuring in human serum of free thyroxine (fT4). The limit of detection is 20 fM
      or 16 fg/ml at the assay time <30 min with the dynamic range of 3 orders.
      Besides, we present the results of first characterization of kinetic parameters
      of interaction between free thyroxine and monoclonal antibody, as well as of
      competitive relationship between fT4 and fT4-biotin. The proposed universal
      platform can be used for ultrasensitive detection of small molecules in human in
      vitro diagnostics, veterinary, biosafety and counter-terrorism, food quality
      control, environmental monitoring, etc., as well as for search of new, previously
      undetectable, diagnostic markers in medicine.

PMID- 30193631
TI  - An instantaneous near-infrared trimethyl lock based fluorescent probe for
      biothiols with a large Stokes shift.
AB  - Using trimethyl lock as a useful mean, a selective and sensitive fluorescent
      probe was developed for the detection of biothiols with an emission in near
      infrared spectral region (694 nm) and a large Stokes shift (129 nm). The inserted
      trimethyl lock between the fluorophore and the sensing group, 2, 4
      dinitrobenzensulfonate, highly improved the response rate of this probe toward
      GSH because the unfavorable steric interactions between three methyl groups
      resulted in an extremely rapid intramolecular lactonization reaction to form a
      hydrocoumarin. This probe displayed an instantaneous response (within seconds) to
      GSH at a very low concentration in aqueous medium and the detection limit was as
      low as 2.5 nM based on S/N = 3. The fluorescence intensity of the solution of
      probe 1 at 694 nm displayed a good linearity (R = 0.9917) with the concentration
      of GSH in a range of 0.0-5.0 MUM. Importantly, this probe exhibited a good
      performance in detecting biothiols in serum samples, living cells and organism.

PMID- 30193632
TI  - Chemical nanosensors based on molecularly-imprinted polymers doped with silver
      nanoparticles for the rapid detection of caffeine in wastewater.
AB  - Caffeine is a common pharmaceutical and personal care product pollutant in
      wastewater. This work offers rapid and single-step detection of caffeine in an
      aquatic matrix based on high performance surface-enhanced Raman scattering
      (SERS). Novel chemical SERS nanosensors were developed employing molecularly
      imprinted polymer (MIP) particles loaded with Ag nanoparticles (AgNPs) using
      precipitation polymerization to form AgNPs@MIP nanocomposites. Theophylline was
      applied as a dummy template molecule in the synthesis process due to its high
      structural similarity with caffeine and greater availability. The nanocomposite
      was characterized by Fourier transform infrared spectroscopy(FTIR), X-ray
      diffraction(XRD), and ultraviolet-visible (UV-vis) spectroscopy. Static and
      kinetic adsorption testing demonstrated the specific affinity of AgNPs@MIP
      nanocomposites for caffeine and a rapid adsorption equilibration rate. Moreover,
      a simple solid phase extraction cartridge comprising AgNPs@MIP nanocomposites as
      adsorbents (AgNPs@MISPE), a syringe, and a removable microporous membrane were
      employed to detect the SERS signal of caffeine. The AgNPs@MISPE was used to
      detect caffeine with excellent uniformity (relative standard deviation, RSD =
      4.8%) and good repeatability (RSD = 8.7%). The separation and detection processes
      were integrated into a single step, and the overall analysis time was 23 min. The
      detection limit was 100 ng L-1, which is less than the caffeine content reported
      in many rivers. The experimental results demonstrate that the proposed chemical
      nanosensors are a low-cost and reliable tool for the rapid screening of caffeine
      in wastewater or other aquatic matrices.

PMID- 30193633
TI  - Development and validation of ultra-high performance supercritical fluid
      chromatography method for quantitative determination of nine sunscreens in
      cosmetic samples.
AB  - A fast and simple utra-high performance supercritical fluid chromatography
      (UHPSFC) method has been developed for the determination of nine sunscreens (UV
      filters), namely 2-ethylhexyl-2-hydroxybenzoate (ES), ethylhexyl-methoxycinnamate
      (EMC), benzophenone-3 (BZ3), octocrylene (OCR), bis-ethylhexyloxyphenol
      methoxyphenyl triazine (EMT), butyl-methoxydibenzoyl-methane (BDM), diethylamino
      hydroxybenzoyl-hexyl-benzoate (DHB), ethylhexyl-triazone (ET), and diethylhexyl
      butamido-triazone (DBT) in cosmetic samples. The separation was achieved with
      Acquity UPC2 Torus 2-PIC (100 * 3.0 mm, 1.7 MUm) column. The influence of key
      chromatographic parameters on resolution was evaluated. The optimal mobile phase
      was a gradient mixture of carbon dioxide and methanol containing ammonium
      acetate, at flow rate 1.2 mL min-1. The back-pressure of the system was set to
      150 bar and the temperature to 40  degrees C. The compounds were determined with
      diode-array detection at 280 nm, 305 nm and 340 nm depending on absorbance
      maxima. The proposed UHPSFC method provided separation of the nine target
      sunscreens within 2.5 min without labor-consuming sample pretreatment procedure.
      The method was validated according to the concept of the total error and the
      accuracy profile. The inter-laboratory reproducibility was evaluated between two
      independent laboratories (in France and Czech Republic). The reliability of the
      developed method was shown by application to commercial sunscreen-containing
      cosmetic sample obtained from French market. The measured limits of
      quantification showed the suitability of the proposed method for determination of
      UV filters considering the European Union requirements.

PMID- 30193634
TI  - Evaluation of boronate affinity solid-phase extraction coupled in-line to
      capillary isoelectric focusing for the analysis of catecholamines in urine.
AB  - In this study, a new miniaturized and integrated analytical system was developed
      based on the in-line coupling of boronate affinity solid phase extraction with
      capillary isoelectric focusing separation and UV detection. This original
      coupling takes advantage of the selective enrichment of cis-diol-containing
      compounds using a boronate affinity sorbent and the exceptional focusing features
      of isoelectric focusing process. Such coupling has been used for
      preconcentration/purification and separation of urinary catecholamines (dopamine,
      adrenaline and noradrenaline) as proof of concept. Poly(glycidyl methacrylate-co
      ethylene dimethacrylate) monolithic capillary column (8 cm) was chosen as solid
      phase extraction support due to its good chemical stability and its easy and
      versatile surface functionalization. Characterization of the miniaturized
      boronate affinity monolith column (MUBAMC) was done by frontal affinity
      chromatography. An active-site amount of about 0.16 nmol cm-1 (75 MUm i. d.) of
      phenyl boronic acid groups and Kd values ranging from 224 to 106 MUM were
      obtained for catechol and catecholamines. A high loading volume (up to 15 times
      the affinity column volume) can be introduced with quantitative recovery yields.
      Optimization of the in-line coupling concerned the adaptation of (i) the MUBAMC
      volume, (i.e. length and inner diameter of the monolithic column) for loading of
      large sample volumes and (ii) the CIEF experimental conditions. The ampholyte
      mixture was adapted (i.e. nature and concentration of carrier ampholytes, volume
      of sacrificial electrolytes) in order to ensure elution and separation of
      catecholamines and to decrease limit of detection down to 10-20 ng ml-1. The
      optimized method was applied to analyze urine samples.

PMID- 30193635
TI  - Magnetic framework composite as sorbent for magnetic solid phase extraction
      coupled with high performance liquid chromatography for simultaneous extraction
      and determination of tricyclic antidepressants.
AB  - In this study, magnetic framework composites (MFCs) (Fe3O4@TMU-10) microspheres
      were successfully fabricated and applied as an effective sorbent for
      preconcentration of the two model tricyclic antidepressants (TCAs) amitriptyline
      and imipramine from biological samples. MFCs were fabricated by a step-by-step
      assembly, novel, simple and efficient strategy. The shell thickness of the Metal
      organic frameworks (MOFs) could also be easily controlled by tuning the number of
      assembly cycles. By coupling magnetic solid-phase extraction (MSPE) with high
      performance liquid chromatography with UV detector (HPLC-UV), a simple, reliable,
      fast, sensitive and cost-effective method for simultaneous determination of TCAs
      was developed. Under optimal conditions, the preconcentration factors and
      relative recoveries of the studied compounds were obtained in the range of 43-50
      and 90.5-99.0% respectively. The calibration curves were obtained in the range of
      5-800 MUg L-1 with reasonable linearity (R2 > 0.9904) and the limits of detection
      (LODs) ranged between 2 and 4 MUg L-1 (based on S/N = 3). The relative standard
      deviations of intra- and inter-day tests ranged from 3.1 to 4.6% and from 4.3 to
      5.2%, respectively. The results demonstrate that Fe3O4@TMU-10 core-shell magnetic
      microspheres combine advantages of MOFs and magnetic nanoparticles, and are the
      promising sorbents for rapid and efficient extraction of target analytes from
      urine and plasma complex biological samples.

PMID- 30193636
TI  - Capillary electrophoretic mobility shift displacement assay for the assessment of
      weak drug-protein interactions.
AB  - Only few reports describe the use of capillary electrophoresis in the context of
      Fragment Based Drug Discovery (FBDD). In this paper, we will present a generic,
      fully automated, microscale electrophoretic mobility shift displacement assay
      that can be used in FBDD for primary screening of weak biomolecular interactions
      between fragments and target protein. The accuracy and reliability of the present
      method was demonstrated by measuring the IC50 value of two known fragments
      inhibiting thrombin, namely benzamidine and p-aminobenzamidine and a relatively
      weak inhibitor, nafamostat. Furthermore, we built a small chemical library to
      evaluate the performance and the advantage of our newly developed screening
      bioassay compared to the direct affinity capillary electrophoresis-binding assay.
      The results demonstrate the high discriminatory power of the method and above all
      its ability to screen neutral, negatively or positively charged molecules, as
      well as molecules that have no or low UV-VIS absorbance, greatly expanding the
      scope of the assay. Finally, we proved that this approach is able to discriminate
      between reversible and irreversible binders. Altogether, this work demonstrates
      that capillary electrophoresis could constitute an important added value in the
      arsenal used to screen fragments in drug discovery.

PMID- 30193637
TI  - Current trends on the determination of organic UV filters in environmental water
      samples based on microextraction techniques - A review.
AB  - UV filters are a group of cosmetic ingredients commonly used in a wide variety of
      cosmetic products to protect users from UV solar radiation. They belong to
      different chemical families, such as benzophenones, p-aminobenzoates,
      salicylates, cinnamates, benzotriazoles, benzimidazoles, camphor derivatives,
      triazines, etc. These cosmetic ingredients are considered as emerging
      contaminants since they easily reach the aquatic environment, where they are
      accumulated causing harmful effects in the flora and fauna despite being present
      at the ng L-1 level. Therefore, the development of sensitive and selective
      analytical methods for their environmental surveillance monitoring is of high
      interest. In this sense, the so-called microextraction techniques play an
      important role in the sample preparation of environmental water samples. The aim
      of this review is to compile and discuss the published papers concerning
      analytical methods for the determination of organic UV filters in environmental
      water samples based on the use of both sorbent-based and solvent-based
      microextraction techniques. A special emphasis has been placed on the current
      trends, i.e., the use of novel (nano)materials and solvents, and the application
      of the most advanced approaches. The increase in the number of published articles
      related to the use of these miniaturized techniques reflects their high potential
      in the determination of organic UV filters in environmental water samples.

PMID- 30193639
TI  - Simultaneous electrochemical sensing of warfarin and maycophenolic acid in
      biological samples.
AB  - In this study, for the first time a rapid, selective and highly sensitive method
      was developed for simultaneous determination of warfarin and mycophenolic acid
      using carbon paste electrode modified by beta-cyclodextrin/multi-walled carbon
      nanotubes/cobalt oxide nanoparticles (beta-CD/MWCNTs/Co3O4NPs/CPE). The oxidation
      peaks of desired drugs was separated enough using the constructed electrode.
      Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) were utilized
      for study the electrochemical response of the fabricated electrode and its
      surface modification was investigated by electrochemical impedance spectroscopy
      (EIS). Under optimal conditions, the adsorptive stripping voltammetric responses
      were linear in the concentration ranges 0.05-150 MUM and 0.5-200 MUM for WAR and
      MPA, respectively. The correlation coefficients were greater than 0.99. The
      limits of detection for WAR and MPA were 0.02 and 0.03 MUM. The fabricated
      electrode was applied for the simultaneous determination of WAR and MPA in urine
      and human serum samples with satisfactory results.

PMID- 30193638
TI  - Impedance-based sensor for potassium ions.
AB  - A conductometric sensor for potassium ions in solution is presented.
      Interdigitated, planar gold electrodes were coated with a potassium-selective
      polymer membrane composed of a poly(vinyl chloride) matrix with about 65 wt% of
      plasticiser and 2-5 wt% of a potassium-selective ionophore. The impedance of the
      membrane was measured, using the electrodes as a transducer, and related to the
      concentration of potassium in a sample solution in contact with the membrane.
      Sensitivity was optimised by varying the sensor components, and selectivity for
      potassium over sodium was also shown. The resulting devices are compact,
      miniature, robust sensors which, by means of impedance measurements, eliminate
      the need for a reference electrode. The sensor was tested for potassium
      concentration changes of 2 mM across the clinically relevant range of 2.7-18.7
      mM.

PMID- 30193640
TI  - Dual triggers induced disassembly of DNA polymer decorated silver nanoparticle
      for ultrasensitive electrochemical Pb2+ detection.
AB  - In this work, a new label-free biosensor based on highly effective decomposition
      of a branched DNA polymer and target-transition recycling amplification was
      designed for ultrasensitive electrochemical determination of lead ion (Pb2+). The
      branched DNA polymer formed by hybridization chain reaction (HCR) was first
      immobilized on electrode and served as the carrier for loading abundant silver
      nanoparticle (AgNPs) to generate an extremely high initial current signal output.
      Then, the molecular triggers T1 and T2, which were produced through a target
      transition recycling amplification, could respectively disassemble the backbone
      and side chain of the branched DNA polymer with remarkably decreased current for
      sensitive detection of Pb2+. Compared with traditional one-trigger induced
      disassembly strategy, the proposed approach exhibited higher decomposition
      efficiency. The experimental data showed that this developed biosensor had a
      superior performance for Pb2+ detection with a low detection limit down to 0.24
      pM. Furthermore, the established strategy set up a new way to achieve the
      ultrasensitive detection of other metal ions.

PMID- 30193641
TI  - A new bifunctional nanostructure based on Two-Dimensional nanolayered of Co(OH)2
      exfoliated graphitic carbon nitride as a high performance enzyme-less glucose
      sensor: Impedimetric and amperometric detection.
AB  - A novel non-enzymatic glucose sensor was constructed based on the nanolayered
      Co(OH)2 deposited on polymeric graphitic carbon nitride (Co(OH)2-g-C3N4) via
      chemical bath deposition. The two-dimensional nanocomposite was used to modify a
      carbon paste electrode and its electrochemical performance of electrode was
      carefully evaluated. The electrochemical oxidation of glucose at modified
      electrode was studied by cyclic voltammetry (CV) and electrochemical impedance
      spectroscopy (EIS) in 0.2 M KOH. It revealed a remarkable electrocatalytic
      behavior and noticeably synergistic effect as a result of decent exfoliation of
      graphitic carbon nitride in the presence of Co(OH)2. The amperometric response
      achieved by the modified electrode showed two calibration ranges with an
      excellent selectivity. A single-frequency impedance method was applied for
      glucose determination as an alternative to conventional EIS methods. The
      developed sensor represents a high sensitivity, wide concentration range (25 MUM 
      420.0 mM by impedimetry and 6.6-9800 MUM by amperometry), and high
      reproducibility. The modified electrode showed a good selectivity for glucose
      over potentially interfering materials such as dopamine, ascorbic acid, urea, and
      uric acid. Finally, the Co(OH)2-g-C3N4-CPE was utilized for quantification of
      glucose in blood serum samples.

PMID- 30193642
TI  - Optimization of extraction methods for comprehensive profiling of perfluoroalkyl
      and polyfluoroalkyl substances in firefighting foam impacted soils.
AB  - The comprehensive analysis of aqueous film forming foam (AFFF) formulations has
      led in recent years to the discovery of novel classes of perfluoroalkyl and
      polyfluoroalkyl substances (PFASs). Whether the pre-existing analytical methods
      for historically monitored PFASs, including perfluorooctane sulfonate (PFOS),
      could be transferable to a large breadth of newly identified PFASs remains,
      however, an open question. Data from various lines of evidence indicate that
      current extraction procedures previously validated with anionic and neutral PFASs
      may seriously underperform for many cationic and zwitterionic PFASs. The
      extraction efficiency and instrumental response could be strongly matrix
      dependent, which may preclude a robust analysis. The present study sought to
      investigate a suitable sample preparation procedure for the analysis of anionic,
      cationic, and zwitterionic PFASs in soil samples. In total, 86 PFASs,
      representing 24 chemical classes previously discovered in AFFF formulations or at
      AFFF-impacted sites, were evaluated. The merits and limitations of various
      extraction media were examined using an AFFF-impacted field-weathered loam soil,
      as well as a background loam soil amended with AFFFs in-house. Methanol with
      hydrochloric acid provided excellent recoveries for most cationic and
      zwitterionic PFASs, including fluorotelomer sulfonamidoalkyl betaines (e.g., 6:2
      FTAB) and fluorotelomer betaines (e.g., 9:1:2 FTB), yet performed less
      satisfactorily for certain anionic PFASs, and may also cause conversion of some
      PFASs. Sequential extractions using methanol with ammonium acetate exhibited
      limited matrix effects and suitable recoveries of PFASs from soils of diverse
      textural classes and organic matter content. The newly-developed extraction
      method presented the best option for future in-depth characterization of PFASs at
      AFFF-impacted sites.

PMID- 30193643
TI  - Kinetic study of continuous liquid-liquid extraction of wine with real-time
      detection.
AB  - Kinetic optimization of continuous liquid-liquid extraction (CLLE) can shorten
      sample preparation times and reduce losses of labile or volatile analytes. Here,
      we coupled a downscaled CLLE apparatus with atmospheric pressure chemical
      ionization interface of triple quadrupole mass spectrometer. Real-time sampling
      was guided by an Arduino-based programmable logic controller. The recorded
      datasets were processed to compute the extraction rate constants for the target
      analytes. The extraction time in subsequent on-line experiments was set to 180
      min as a compromise between the reduction of the analysis time and maximizing its
      yield. Interestingly, off-line analysis of the extract produced different results
      than on-line analysis pointing to the immanent degradation of the collected
      extract aliquots. Next, we implemented this hyphenated system in the analysis of
      red wine samples, which were stored during different periods of time after
      opening the bottle. The results reveal differences in the depletion of the
      volatile wine components during storage.

PMID- 30193644
TI  - Determination of volatile fatty acids in digestate by solvent extraction with
      dimethyl carbonate and gas chromatography-mass spectrometry.
AB  - Volatile fatty acids (VFAs) are among the most important parameters in process
      monitoring of anaerobic digestion plants for biogas production. The concentration
      of single VFA species is typically determined by direct injection of the
      acidified aqueous phase of digestate samples into GC-FID. Analysis of dimethyl
      carbonate extracts was investigated as an alternative method consisting of a
      simple and rapid in-vial procedure of acidification and solvent extraction of the
      sample, followed by centrifugation and GC-MS analysis. The principal figures of
      merit resulting from internal standard calibration were comparable to those
      proposed for the direct analysis of aqueous digestate, while the analysis of real
      samples did not provide statistically significant differences between the two
      methods according to parametric and non-parametric tests. Procedural aspects
      including sample amount and solid removal improved with dimethyl carbonate, while
      GC contamination was reduced. The method was applied to seventeen samples from
      fully operating anaerobic digesters fed with various feedstocks and enabled the
      individuation of high probability of system stress through the values of total
      VFA, propanoic acid, longer chained VFA concentrations and the ratio between
      acetic and propanoic acid concentrations. The use of dimethyl carbonate allowed
      the detection of alicyclic and aromatic acids that could represent new molecular
      markers in assessing the origin of feed and process conditions.

PMID- 30193645
TI  - Letter from the Editors.

PMID- 30193646
TI  - Letter from the Guest Editors.

PMID- 30193647
TI  - SPECT/CT in Postoperative Hand and Wrist Pain.
AB  - In this review we summarize the current evidence and experience regarding the
      performance of SPECT/CT in the evaluation of patients with postoperative painful
      wrist or hand. There is a wide range of operative wrist and hand interventions
      due to congenital, traumatic, degenerative, or inflammatory diseases. A
      significant number of patients suffer from pain after operative procedures.
      Several imaging modalities have been used to evaluate the reason for painful
      postoperative wrists like standard conventional x-rays, ultrasound, CT, MRI, or
      bone scintigraphy. In the last decade, bone SPECT/CT has offered a new approach
      in combining metabolic and morphologic cross-sectional information in patients
      with painful postoperative wrists and is increasingly used if standard imaging
      fails to identify the pain generator. SPECT/CT is less hampered by artifacts
      caused by metallic implants and shows more details of the cortical bone compared
      with MRI. MRI is generally superior regarding visualization of soft tissue
      structures like tendons, synovia, cartilage, muscles, and ligaments. SPECT/CT
      arthrography has been established to enable the assessment of cartilage and
      ligament tears.

PMID- 30193648
TI  - Bone SPECT/CT in Postoperative Spine.
AB  - Back pain is a common problem and the diagnosis and treatment depend on the
      clinical presentation, yet overlap between pain syndromes is common. Imaging of
      patients with chronic back pain in both pre- and postoperative scenarios include
      radiological, radionuclide, and hybrid techniques. In general, these techniques
      have their own advantages and limitations. The aim of surgery is to eliminate
      pathologic segmental motion and accompanying symptoms, especially pain. However,
      surgical procedures are not without complications and localizing the cause of the
      pain is often challenging. Radiobisphosphonate bone SPECT/CT is reported to be
      useful in evaluating benign orthopedic conditions and it often provides valuable
      information such as accurate localization and characterization of bone
      abnormalities. In this review, routinely used spinal surgical techniques and
      procedures are discussed, as well as the acute and delayed complications related
      to spinal surgery, the role of conventional imaging, and the potential uses of
      radionuclide bone SPECT/CT to diagnose pseudoarthrosis, cage subsidence,
      loosening and misalignment, hardware failure, and postoperative infection.

PMID- 30193649
TI  - SPECT/CT in Postoperative Painful Hip Arthroplasty.
AB  - Consecutive milestones in hip arthroplasty design and surgical technique have
      contributed to the successful and cost-effective intervention this procedure has
      become today in maintaining mobility and quality of life in patients with
      osteoarthritis, fracture, or other hip conditions. With the increasing prevalence
      of hip joint replacements, the need for improved diagnostic imaging tools to
      guide revision surgery has risen in parallel. Over the last few years, promising
      data have emerged on the potential role of bone SPECT/CT imaging in the
      assessment of patients with recurrent pain after arthroplasty. This review
      summarizes the trends in hip arthroplasty surgery (partial vs total arthroplasty;
      cemented vs cementless arthroplasty; resurfacing arthroplasty) and prosthesis
      design (bearing materials; stem designs) over the last decade. In particular, the
      impact on the biomechanics and interpretation of bone SPECT/CT findings is
      discussed, with emphasis on integrative reporting in the following frequently
      encountered conditions: lysis/aseptic loosening, septic loosening, heterotopic
      ossification, periprosthetic fracture, tendinopathies, and adverse local tissue
      reactions. Based on the available literature data, bone SPECT/CT is increasingly
      being used as second-line imaging modality when conventional investigations are
      nondiagnostic. Further outcome research is warranted to examine whether this
      technique could be used earlier in patient management.

PMID- 30193650
TI  - SPECT/CT in the Postoperative Painful Knee.
AB  - This review summarizes the role of SPECT/CT in patients with a painful
      postoperative knee and describes typical diagnostic criteria in these patients.
      Pain after knee surgery is common and is influenced by the underlying pathology,
      the type of surgery, and the patient. Knee joint-preserving surgery includes
      osteotomy, ligament reconstruction, meniscus surgery, and cartilage repair
      procedures, often used in combination. Knee arthroplasty procedures consist of
      unicondylar, patellofemoral, and primary or revision total knee prosthesis. In
      patients with pain after knee joint-preserving surgery, MRI remains the reference
      standard. After ligament reconstruction, CT can evaluate postoperative tunnel
      positioning, and bone SPECT/CT can contribute by assessing overloading or
      biodegradation problems. After meniscal or cartilage surgery, SPECT/CT can be
      particularly helpful to identify compartment overloading or nonhealing chondral
      or osteochondral lesions as cause of pain. SPECT/CT arthrography can assess
      cartilage damage at an early stage due to altered biomechanical forces. After
      corrective osteotomy of the knee, SPECT/CT can reveal complications such as
      overloading, nonunion, or patellofemoral problems. After arthroplasty,
      conventional radiographs lack both sensitivity to detect aseptic loosening and
      specificity in differentiating aseptic from infectious loosening. Secondly,
      hardware-induced artifacts still hamper CT and MRI, despite improving and
      increasingly available metal artifact reduction techniques. Bone scintigraphy is
      a proven useful adjunct to conventional radiography and MRI to reveal the pain
      generator and is less hampered by artifacts from metallic implants compared with
      CT and MRI. Nevertheless, the optimal imaging strategy in evaluating
      complications after knee arthroplasty is still a matter of debate. Although the
      evidence of the use of BS SPECT/CT is still limited, it is growing steadily. In
      particular, recent data on specific uptake patterns in tibial and femoral zones
      after total knee arthroplasty and the impact of integrating biomechanics into the
      assessment of SPECT/CT appear promising, but more research is needed.

PMID- 30193651
TI  - SPECT/CT in Postoperative Foot and Ankle Pain.
AB  - Postoperative pain is a clinically relevant issue in orthopedic patients,
      affecting more than 40% 1 year after foot and ankle surgery. Because of the very
      complex anatomy with many different joints and several motion axes, clinical
      examination and conventional imaging are sometimes not sufficient to identify a
      local pain generator. Local uptake of bone-seeking radiopharmaceuticals is known
      to correlate accurately with sites of pain generating foci and, thus, bone
      scintigraphy has been an established method to evaluate these respective patients
      for many years. However, the specificity is rather low if only planar images are
      acquired. The development of SPECT and especially of hybrid SPECT and CT imaging
      has significantly enhanced the specificity of this technique. The combination of
      both functional and morphological imaging, ideally performed with a dedicated
      SPECT/CT system to minimize misregistration owing to motion artifacts and to
      enhance image quality by attenuation correction, allows an early and reliable
      detection of pathologic bone processes, even in patients where radiological
      imaging with MRI or CT is hampered by metal implants. In diabetic patients with a
      neuropathic Charcot osteoarthropathy, infection can be differentiated from
      inflammatory bone alterations (causing bone marrow edema) almost certainly using
      SPECT/CT with radiolabeled white blood cells and antigranulocyte antibodies,
      allowing an individual and precise treatment planning either in the initial
      course of the disease or even after surgery. This article reviews the most
      frequent clinical challenges in patients after foot and ankle surgery, including
      a description of the various surgical procedures, the different imaging options
      with their advantages and disadvantages, and aims to integrate bone SPECT/CT into
      the clinical diagnostic workup.

PMID- 30193652
TI  - SPECT/CT in Postoperative Shoulder Pain.
AB  - Over the last 2 decades, the incidence of prosthetic shoulder replacements has
      increased considerably, leading to a rising number of complications and
      reoperations. In this article, we review how SPECT/CT can be of significant
      clinical value for shoulder surgeons. Bone SPECT/CT can provide the correct
      diagnosis for different types of mechanical complications: glenoiditis after
      hemiarthroplasty, glenoidal loosening after total shoulder arthroplasty, and
      scapular notching after reverse shoulder arthroplasty. Various nuclear medicine
      methods are available for detecting prosthesis infection. In our experience,
      labeled white blood cell scintigraphy combined with bone marrow scintigraphy is
      the reference standard. FDG-PET may be useful in case of discordance between the
      white blood cell scan and the clinical context and complementary test results.

PMID- 30193653
TI  - [Lifestyle medicine need to be promoted - Green prescription].

PMID- 30193654
TI  - [Can artificial intelligence be used for assessing a patient with alcohol
      dependence?]

PMID- 30193655
TI  - A novel FTATM elute card collection method that improves direct DNA amplification
      from bloodstained concrete.
AB  - Concrete is a common construction material found in residential and commercial
      buildings, bridges and parking lots that is a composite matrix containing
      aggregate held together with cement. The porous nature of concrete can make the
      collection and genotyping of biological fluids, such as blood, challenging.
      Forensic evidence can become embedded within the matrix, potentially reducing the
      amount of DNA available for analysis. In forensic science, "direct" amplification
      refers to a genotyping method that amplifies a DNA profile directly from a sample
      without DNA extraction, saving time and money. We investigated a novel
      application of WhatmanTM FTATM Elute cards in their ability to directly amplify
      PowerPlex(r) Fusion and Y23 profiles from minute amounts of blood that had been
      deposited on different concrete structures. In comparison to traditional
      collection methods, directly profiling blood stained construction materials using
      FTATM Elute cards increased the percentage loci amplified and significantly
      improved both allele peak height and peak height ratio while reducing allelic
      drop-out. FTATM Elute cards can provide a reliable, inexpensive and superior
      alternative to traditional methods.

PMID- 30193656
TI  - A preliminary assessment of the effect of PreCRTM DNA repair treatment on mixture
      ratios in two person mixtures.
AB  - In this study, DNA extracted from known buccal samples was combined into two
      component mixture samples. These were subjected to UV exposure prior to their
      amplification with the Promega PowerPlex(r) 16HS amplification kit, and
      subsequent capillary electrophoresis on the ABI 3130xl instrument. Damaged
      samples were subjected to enzymatic repair treatment and retested to assess the
      amount of repair. Data showed that there is fidelity associated with the
      application with profile concordance after its use, and a corresponding increase
      in the amount of recovered alleles post damage. Results also showed changes in
      the stochastic relationship between mixture components that appear to be induced
      by the repair process itself. The mixture ratios of DNA samples were altered from
      an approximate original 1:3 ratio, to a ratio of 1:2 or greater. This variation
      can have a significant effect regarding the ability to reliably de-convolute DNA
      mixtures that have been subjected to the repair process.

PMID- 30193657
TI  - Are DNA data a valid source to study the spatial behavior of unknown offenders?
AB  - Studying the spatial behaviour of unknown offenders (i.e. undetected offenders)
      is difficult, because police recorded crime data do not contain information about
      these offenders. Recently, forensic DNA data has been used to study unknown
      offenders. However, DNA data are only a subset of the crimes committed by unknown
      offenders stored in police recorded crime data. To establish the suitability of
      DNA data for studying the spatial offending behaviour of unknown offenders, we
      examine the concentration and spatial similarity of detected but unsolved crimes
      in police recorded crime data (N = 181,483) and DNA data (N = 1913) over 27
      Belgian judicial districts for four crime types. We established spatial
      similarity for certain crime types (in some districts). This offers opportunities
      for DNA data to be used to study unknown offenders' spatial offending behaviour.
      Implications for theory and research are discussed.

PMID- 30193658
TI  - Impact of aging on fingerprint ridge density: Anthropometry and forensic
      implications in sex inference.
AB  - The variation in the epidermal ridge's width between the sexes, during various
      growth stages, and among different populations has been previously assessed.
      However, the changes that occur with aging are barely known. The goal of this
      study was to analyse the degree of variation in epidermal ridge width due to
      aging. So that, fingerprint ridge density was estimated to establish their
      relationship with body and hand size changes that typically occur in adulthood.
      In this study, a sample of 213 adults of both sexes from a Spanish native
      population of different age ranges-18-30 years old ("junior" group) and 50-66
      years old ("senior" group)-was used. Ridge density was assessed in three counting
      areas of the distal phalanx of each finger (radial, ulnar, and proximal). Height,
      weight, and a set of anthropometric measurements for both hands were also taken.
      Our results show that ridge density is higher in females than males throughout
      adulthood and decreases with aging in the radial and ulnar areas (as the hands
      widen) but not in the proximal region. Thus, a relationship between hand
      dimensions and ridge density was found. The data indicate that aging changes may
      conceal the recognized sex differences in ridge density, and so a better
      understanding of the topological variations in the epidermal ridge width
      throughout the life cycle and the factors involved would facilitate the
      interpretation of the differences between the sexes and different age groups.

PMID- 30193659
TI  - The United Kingdom and Ireland association of forensic toxicologists forensic
      toxicology laboratory guidelines (2018).
AB  - In 2010, the United Kingdom and Ireland Association of Forensic Toxicologists
      (UKIAFT) created forensic toxicology laboratory guidelines. This represents a
      revision of those guidelines as a result of the changing toxicological and
      technical landscape.

PMID- 30193660
TI  - A comparative study of standing fleshed foot and walking and jumping bare
      footprint measurements.
AB  - Approximating true fleshed foot length and forefoot width from crime scene
      footprints is primarily based on anecdotal observations and fails to consider
      effects of different dynamic activities on footprint morphology. A literature
      search revealed numerous variables influencing footprint formation including
      whether the print was formed statically or dynamically. The aim of this study was
      to investigate if length and width measurements of the fleshed foot differ to the
      same measurements collected from walking and jumping footprints. Measurements of
      standing right foot length and forefoot width were collected from thirteen
      participants. Walking and jumping right footprints were then obtained using an
      Inkless Shoeprint Kit and digitally measured with GNU Image Manipulation
      Programme. Descriptive analysis compared standing fleshed foot length and
      forefoot width against the same measurements taken from walking and jumping
      footprints with and without ghosting. Results suggested walking footprint length
      with ghosting (x- = 268.61 mm) was greater than standing fleshed foot length (x-
      = 264.3 mm) and jumping footprint length with ghosting (x- = 261.57 mm). However,
      standing fleshed foot length was found to be greater than walking (x- = 254.85
      mm) or jumping (x- = 255.63 mm) footprint lengths without ghosting. Forefoot
      widths showed standing fleshed foot width (x- = 105.66 mm) was greater than
      walking (x- = 95.63 mm) or jumping (x- = 98.03 mm) footprint widths. This study
      identifies variation in measurements of the standing fleshed foot and those of
      walking and jumping footprints, including variability between different dynamic
      states.

PMID- 30193661
TI  - Extraction and isolation of cannabinoids from marijuana seizures and
      characterization by 1H NMR allied to chemometric tools.
AB  - Marijuana, a drug derived from the Cannabis sativa L. plant, is the world's most
      consumed illicit drug. In this paper, a total of 156 marijuana samples seized in
      the state of Espirito Santo (ES), Brazil were studied and analysed by proton
      nuclear magnetic resonance (1H NMR) spectroscopy to identify the major
      cannabinoids present. A crude extract of all samples was purified using high
      performance liquid chromatography so that these compounds could serve as
      reference substances. Nine fractions were obtained and analysed by 1H NMR and gas
      chromatography-mass spectrometry (GC-MS), with five presented cannabinoids. ?9
      THC (Delta9-trans-tetrahydrocannabinol), ?9-THCA (?9-tetrahydrocannabinolic
      acid), ?8-THC (?8-tetrahydrocannabinol), 11-hydroxycannabinol, CBV
      (cannabivarin), and CBN (cannabinol) were found, and their chemical structures
      were confirmed by GC-MS. The latter compound was obtained with high purity
      (~100%), while the others were obtained as less complex mixtures with purity
      higher than 75% (except for Delta8-THC). Principal component analysis (PCA) was
      used on the 1H NMR spectra of the 156 samples, and it was found that the samples
      were grouped according to the months, differentiating into two groups (from July
      2014 to January 2015 and from February 2015 to July 2015), where non-grouping was
      observed from four macro-regions of the ES state (North, Central, Metropolitan,
      and South). The chemical profile of the seized samples was correlated to the 1H
      NMR spectrum of an isolated CBN sub-fraction, in which the group formed by
      samples seized in the year 2015 presented lower CBN content in the chemical
      composition. From the PCA score plot, two groups of samples were confirmed using
      the partial least squares discriminant analysis and orthogonal projections to
      latent structures classification methods.

PMID- 30193662
TI  - Is Australia ready for fentanyl?

PMID- 30193663
TI  - Fingermark visualisation on metal surfaces: An initial investigation of the
      influence of surface condition on process effectiveness.
AB  - Fingermark recovery from metal surfaces is an area of operational interest, both
      from the association of metals with weapons used in violent crime and from the
      increasing incidence in metal theft. This paper reports a feasibility study into
      the effectiveness of a range of fingermark visualisation processes in developing
      fingermarks on clean metals (brass, bronze and stainless steel), and on the same
      metals after prolonged exposure to an outdoor environment. Scanning electron
      microscopy (SEM) was used to investigate how the surface type and condition could
      influence the development of fingermarks for each of the processes used. It was
      found that the behaviour observed varied between each of the processes
      (cyanoacrylate fuming, LumicyanoTM, gun blueing and carbon-based powder
      suspension). In some cases the chemical composition of the surface affected the
      development of the mark more than the surface condition, and in other cases the
      reverse was true. The best performing processes differed according to the surface
      type and condition, with cyanoacrylate fuming processes working best on brass and
      bronze, and powder suspensions being better on stainless steel. These preliminary
      results reinforce the need to take into account both surface type and condition
      before selection of the most effective fingermark visualisation process and
      demonstrate the value of techniques such as SEM in developing a fundamental
      understanding of the interactions between fingermarks and surfaces.

PMID- 30193664
TI  - Corrigendum to 'Questions, propositions and assessing different levels of
      evidence: Forensic voice comparison in practice'.

PMID- 30193665
TI  - Editorial ETS 2018.

PMID- 30193668
TI  - Social Media Posts and Search Engine Queries as the Canary in the Coal Mine for
      Public Health Surveillance.

PMID- 30193669
TI  - Quantitating the Dose of Physical Activity in Secondary Prevention: Relation of
      Exercise Intensity to Survival.

PMID- 30193670
TI  - Calciphylaxis in Patients With Preserved Renal Function: Worrisome Wounds.

PMID- 30193671
TI  - Hypothyroidism in Clinical Practice.

PMID- 30193672
TI  - Seasonal and Geographic Patterns in Seeking Cardiovascular Health Information: An
      Analysis of the Online Search Trends.
AB  - OBJECTIVE: To ascertain whether temporal and geographic interest in seeking
      cardiovascular disease (CVD) information online follows seasonal and geographic
      patterns similar to those observed in real-world data. METHODS: We searched
      Google Trends for popular search terms relating to CVD. Relative search volumes
      (RSVs) were obtained for the period January 4, 2004, to April 19, 2014, for the
      United States and Australia. We compared average RSVs by month and season and
      used cosinor analysis to test for seasonal variation in RSVs. We also assessed
      correlations between state-level RSVs and CVD burden using an ecological
      correlational design. RESULTS: RSVs were 15% higher in the United States and 45%
      higher in Australia for winter compared with summer (P<.001 for difference for
      both). In the United States, RSVs were 36% higher in February compared with
      August, while in Australia, RSVs were 75% higher in August compared with January.
      On cosinor analysis, we found a significant seasonal variability in RSVs, with
      winter peaks and summer troughs for both the United States and Australia (P<.001
      for zero amplitude test for both). We found a significant correlation between
      state-level RSVs and mortality from CVD (r=0.62; P<.001), heart disease (r=0.58;
      P<.001), coronary heart disease (r=0.48; P<.001), heart failure (r=0.51; P<.001),
      and stroke (r=0.60; P<.001). CONCLUSION: Google search query volumes related to
      CVD follow strong seasonal patterns with winter peaks and summer troughs. There
      is moderate to strong positive correlation between state-level search query
      volumes and burden of CVD mortality.

PMID- 30193673
TI  - Personal Activity Intelligence and Mortality in Patients with Cardiovascular
      Disease: The HUNT Study.
AB  - OBJECTIVE: To test whether Personal Activity Intelligence (PAI), a personalized
      metric of physical activity (PA) tracking, is associated with all-cause and
      cardiovascular disease (CVD) mortality in patients with self-reported CVD and to
      determine whether these associations change depending on whether contemporary PA
      recommendations are met. PATIENTS AND METHODS: A total of 3133 patients with CVD
      (mean [SD] age, 67.6 [10.3] years; 64% men) were followed from the date of
      participation in the Nord-Trondelag Health Study (between January 1, 1984, and
      February 28, 1986) until the date of death or the end of follow-up (December 31,
      2015). The participants' weekly PAI score was calculated and divided into 4
      groups (PAI scores of 0, <=50, 51-99, and >=100). We used Cox proportional
      hazards regression models to estimate hazard ratios for CVD and all-cause
      mortality rates. RESULTS: After mean follow-up of 12.5 years (39,157 person
      years), there were 2936 deaths (94%), including 1936 CVD deaths. Participants
      with weekly PAI scores of 100 or greater had 36% (95% CI, 21%-48%) and 24% (95%
      CI, 10%-35%) lower risk of mortality from CVD and all causes, respectively,
      compared with the inactive group. Participants had similar risk reductions
      associated with their weekly PAI scores regardless of following contemporary PA
      recommendations or not. CONCLUSION: Obtaining a weekly PAI score of at least 100
      was associated with lower mortality risk from CVD and all causes in individuals
      with CVD regardless of whether the current PA recommendations were met.

PMID- 30193675
TI  - Smokeless Tobacco and Cigar and/or Pipe Are Risk Factors for Barrett Esophagus in
      Male Patients With Gastroesophageal Reflux Disease.
AB  - OBJECTIVE: To investigate the effect of smokeless tobacco (ST), cigar and/or pipe
      smoking (CP) on the development of Barrett esophagus (BE) in white male patients
      with gastroesophageal reflux disease (GERD). PATIENTS AND METHODS: A total of
      1015 records of white male adults with BE (cases; n=508) or GERD (controls,
      n=507) were reviewed for lifestyle factors. Logistic regression analyses were
      performed after adjusting for lifestyle factors to assess the effects of ST and
      CP on the risk of developing BE. Differences between patients with BE and those
      with GERD were compared using chi-square and t tests. RESULTS: Patients with BE
      were significantly older than patients with GERD (mean age, 66+/-12 years for
      patients with BE and 55+/-15 years for patients with GERD; P<.001). The odds of
      developing BE in patients who used CS were 1.7 times higher than that in patients
      who never smoked cigarettes (odds ratio [OR], 1.7; 95% CI, 1.3-2.2). It was
      observed that when CS use was combined with either ST or CP use, the odds of
      having BE significantly increased (OR, 2.5; 95% CI, 1.2-5.2; P=.01 and OR, 1.9;
      95% CI, 1.03-3.58; P=.04) in comparison to CS alone. There were no significant
      differences in body mass index and alcohol consumption between BE and GERD
      groups. CONCLUSION: This study suggests that there is indeed an association
      between CS and BE. We believe that this is the first time that ST and CP were
      associated with an even higher odds of developing BE. Further studies are needed
      to investigate whether the use of ST and CP is also associated with an increased
      risk of developing BE-associated adenocarcinoma.

PMID- 30193674
TI  - Aging, Obesity, and the Incidence of Diverticulitis: A Population-Based Study.
AB  - OBJECTIVE: To understand why the population-based incidence of diverticulitis has
      increased over time, we studied temporal changes in age, body mass index (BMI),
      and diverticulitis in Olmsted County, Minnesota. PARTICIPANTS AND METHODS: We
      compared the BMIs of 2967 patients with diverticulitis and 9795 people without
      diverticulitis from January 1, 1980, through December 31, 2007. Because BMI is a
      surrogate for adipose tissue, computed tomographic estimations of abdominal fat
      content were compared between 381 diverticulitis cases and 381 age- and sex
      matched controls. RESULTS: Between 1980 and 2007, the prevalence of obesity
      increased from 12% to 49% in the population and from 19% to 40% in patients with
      diverticulitis (P<.001 for both). Temporal trends in age, BMI, and the increased
      incidence of diverticulitis in people with normal BMI accounted for 48%, 47%, and
      20%, respectively, of corresponding trends in diverticulitis. The secular decline
      in the proportion of people with normal BMI was partly offset by an increased
      incidence of diverticulitis in such people. In the case-control study, BMI was
      greater in cases than in controls (P=.001). However, after incorporating
      abdominal visceral (odds ratio [OR], 2.4; 95% CI, 1.6-3.7) and subcutaneous (OR,
      2.9; 95% CI, 1.7-5.2) fat content (both associated with diverticulitis), BMI was
      associated with lower risk (OR, 0.8; 95% CI, 0.7-0.8) of diverticulitis.
      CONCLUSION: Aging, increasing obesity, and the increased incidence of
      diverticulitis in people with normal BMI account for the temporal increase in
      diverticulitis. Rather than BMI per se, increased abdominal visceral and
      subcutaneous fat are independently associated with diverticulitis. The incidence
      of diverticulitis, which is among the most common gastrointestinal diagnoses in
      hospitalized patients, has increased markedly since 2000. This study suggests
      that aging, increasing obesity, and the increased incidence of diverticulitis in
      people with normal BMI account for the temporal increase in diverticulitis.

PMID- 30193676
TI  - The Mona Lisa Decrypted: Allure of an Imperfect Reality.

PMID- 30193677
TI  - Radiofrequency Ablation Therapy for Large Benign Thyroid Nodules.

PMID- 30193678
TI  - In Reply-Radiofrequency Ablation Therapy for Large Benign Thyroid Nodules.

PMID- 30193679
TI  - In Reply I-Root Causes of the Opioid Crisis.

PMID- 30193680
TI  - The Root Causes of the Current Opioid Crisis.

PMID- 30193681
TI  - In Reply II-Root Causes of Opioid Crisis.

PMID- 30193682
TI  - Correction.

PMID- 30193683
TI  - Corneal Deposits in Multiple Myeloma.

PMID- 30193684
TI  - Diabetic Mastopathy.

PMID- 30193685
TI  - Werner Forssmann: A Pioneer of Interventional Cardiology and Auto
      Experimentation.

PMID- 30193686
TI  - Sugar Maples and Red Tree by Charles Beck.
AB  - Recognizing the contribution art has had in the Mayo Clinic environment since the
      original Mayo Clinic Building was finished in 1914, Mayo Clinic Proceedings
      features some of the numerous works of art displayed throughout the buildings and
      grounds on Mayo Clinic campuses as interpreted by the author.

PMID- 30193688
TI  - The Men and Women in the Arena.

PMID- 30193689
TI  - Nostalgia.

PMID- 30193687
TI  - Hormonal contraception and breast cancer.
AB  - The recent Danish cohort study reported a 20% increased risk of breast cancer
      among current and recent hormonal contraception users. These results are largely
      consistent with previous studies. This study did not report on stage of disease
      at diagnosis, and it is not clear to what extent the apparent increased risk may
      be due to a small advance in the timing of diagnosis. This study did not report
      on the risk associated with the use of a 20-mcg ethinyl estradiol pill. They did
      find an increasing risk in current users of longer duration and an increased risk
      with use of the levonorgestrel intrauterine system-both of these potentially
      important findings have not been consistently found in previous studies and
      require further investigation. The breast cancer effects described now in
      multiple studies wane with time, and in the long term, hormonal contraception use
      has been found not to be associated with any increased total cancer risk.

PMID- 30193690
TI  - Role of Noise in Medical Imaging.

PMID- 30193691
TI  - Re: The effect of prophylactic vertebroplasty on the incidence of proximal
      junctional kyphosis and proximal junctional failure following posterior spinal
      fusion in adult spinal deformity: a 5-year follow-up study.

PMID- 30193692
TI  - Re: The effect of prophylactic vertebroplasty on the incidence of proximal
      junctional kyphosis and proximal junctional failure following posterior spinal
      fusion in adult spinal deformity: a 5-year follow-up study.

PMID- 30193693
TI  - Good prognosis following a PSA bounce after high dose rate brachytherapy and
      external radiotherapy in prostate cancer.
AB  - BACKGROUND: PSA kinetics after curative radiotherapy for prostate cancer is an
      important part of the posttreatment evaluation. We analysed PSA bounce occurrence
      after combined high dose rate brachytherapy (HDR-BT) and external radiotherapy
      (ERT). MATERIAL & METHODS: We analysed 623 patients treated from 1995 to 2008.
      The median age was 66 years (47-79). The median initial PSA was 12 ng/ml (0.1
      224). Neoadjuvant endocrine therapy was given to 429 patients. ERT was given with
      2 Gy fractions to 50 Gy and HDR-BT in two 10 Gy fractions. The median follow-up
      was 11 years (range 2-266 months). PSA bounce was defined as a temporary rise in
      PSA >0.2 ng/ml. PSA failure was defined according to the Phoenix definition.
      RESULTS: PSA bounce occurred in 159 patients (26%), where 56 patients had a
      bounce amplitude >2 ng/ml and 31 patients had multiple bounces. Median time to
      bounce peak was 15 (3-103) months with a median bounce value of 1.5 (0.3
      12)ng/ml. Younger age and lower Gleason scores were associated with PSA bounce.
      In a Cox regression analysis with PSA bounce as a time-dependent covariate and
      adjusted for other prognostic factors, PSA bounce was associated with a lower
      risk for PSA failure (HR = 0.42; 95% confidence interval 0.26-0.70). CONCLUSION:
      PSA bounce after HDR-BT combined with ERT is common and associated with a good
      prognosis. As the relapse risk after an early bounce is very low, the findings
      should alert clinicians not to initiate salvage treatment too early. Research in
      prospective identification of PSA bounce is clinically relevant.

PMID- 30193694
TI  - Australia's Stolen Generations: sorry is not enough.

PMID- 30193695
TI  - Estimating chlamydia prevalence: more difficult than modelling suggests.

PMID- 30193696
TI  - Estimating chlamydia prevalence: more difficult than modelling suggests -
      Authors' reply.

PMID- 30193697
TI  - Migrant health is public health, and public health needs to be political.

PMID- 30193698
TI  - First description of the CTX-M9 gene in Salmonella Paratyphi B in Burkina Faso.

PMID- 30193699
TI  - Tuberculous gumma-like paradoxical cutaneous reaction in a heart transplant
      recipient.

PMID- 30193700
TI  - Editor's Perspectives - September 2018.

PMID- 30193701
TI  - Social Influences on Nicotine-Related Behaviors.
AB  - Cigarette smoking is the leading preventable cause of death in the United States.
      The number of new smokers, specifically among adolescents, has risen rapidly in
      recent years. Thus, understanding the role of social influences on patterns of
      nicotine and tobacco use is important. Clinical studies have addressed the impact
      social relationships such as family members and peers have on smoking acquisition
      and susceptibility. As well, preclinical animal models have examined the impact
      of social factors on drug intake, acquisition, maintenance, and relapse. For
      example, environmental enrichment (EE) is a multi-faceted model that includes
      social factors, exercise, and novelty, among others. This model has elucidated
      addiction-related neurobehavioral effects of these different factors. However,
      there is a dearth of literature examining the impact of social partners on
      nicotine addiction and underlying neural mechanisms. Here we discuss the
      importance of social factors on nicotine addiction vulnerability, and propose new
      directions for addiction research that integrate social aspects of nicotine use.

PMID- 30193702
TI  - Social Modification of Amphetamine Reward.
AB  - Social modification of drug reward in general and amphetamine reward in
      particular is reviewed here. The simplest explanation for the social facilitation
      of drug reward in the conditioned place preference paradigm is the summation of
      drug and social reinforcing effects. However, experimental reports have shown
      that sharing a common pharmacological experience, simultaneously or successively,
      plays a crucial role in the social facilitation of methamphetamine reward.
      Therefore, social facilitation cannot be the simple summation of drug and social
      reinforcing effects. Other social factors, such as the dominant/subordinate
      relation, social defeat, and isolation, also affect drug reward. Because these
      factors induce stress, they may modulate drug effects through stress-induced
      mechanisms. However, it is unclear whether these mechanisms are social experience
      specific or underlie all aversive experiences producing stress. Mutual
      modification of social and drug rewards is also discussed.

PMID- 30193703
TI  - Animal Models of the Impact of Social Stress on Cocaine Use Disorders.
AB  - Cocaine use disorders are strongly influenced by the social conditions prior,
      during, and after exposure to cocaine. In this chapter, we discuss how social
      factors such as early life stress, social rank stress, and environmental stress
      impact vulnerability and resilience to cocaine. The discussion of each animal
      model begins with a brief review of examples from the human literature, which
      provide the psychosocial background these models attempt to capture. We then
      discuss preclinical findings from use of each model, with emphasis on how social
      factors influence cocaine-related behaviors and how sex and age influence the
      behaviors and neurobiology. Models discussed include (1) early life social
      stress, such as maternal separation and neonatal isolation, (2) social defeat
      stress, (3) social hierarchies, and (4) social isolation and environmental
      enrichment. The cocaine-related behaviors reviewed for each of these animal
      models include cocaine-induced conditioned place preference, behavioral
      sensitization, and self-administration. Together, our review suggests that the
      degree of psychosocial stress experienced yields robust effects on cocaine
      related behaviors and neurobiology, and these preclinical findings have
      translational impact for the future of cocaine use disorder treatment.

PMID- 30193704
TI  - Social Factors and Animal Models of Cannabis Use.
AB  - Cannabis, or the dried leaves, stems, and seeds of the hemp plant Cannabis
      sativa, is the most widely used illicit drug in America. Typically smoked,
      vaporized or ingested orally, cannabis is used primarily for recreational
      purposes, though a few synthetic cannabinoids have been approved for medicinal
      treatments. Psychoactive cannabinoids, or the pharmacologically active compounds
      within cannabis, are responsible for producing the infamous "high" sensation,
      characterized by feelings of euphoria and relaxation, though can also provoke
      hallucinations, paranoia and anxiety. Cannabinoids act on G-protein coupled
      receptors in the brain, primarilyCB1 receptors, that typically decrease neural
      activity and modulate transmitter release. Compared to other drugs of abuse,
      cannabis use has minimal health risks and almost no potential for fatal overdose,
      though the trademark method of administration (smoking) has detrimental
      consequences. Chronic heavy use can also lead to changes in memory, cognitive
      deficits, psychosis and dependence. Up to 9% of users can develop a cannabis
      dependence, characterized by a characteristic withdrawal syndrome. The growing
      prevalence of cannabis use has spurred the development of animals models to
      research the neurobehavioral basis of cannabis use. Traditional animal models of
      drug abuse (i.e., conditioned place preference (CPP) and self-administration)
      have historically struggled to establish rewarding or reinforcing effects of
      individual cannabinoid molecules. Decades of research have been needed to reveal
      the appropriate dosage and conditions to promote reward and reinforcement in
      animal models. While the field has made great strides in elucidating the
      mechanisms involved in behavioral pharmacology cannabinoids, the social aspects
      of cannabis use remains underrepresented in animal models. Social interactions
      are vital to the initiation and continuation of cannabis use in humans, and this
      component has yet to be accurately captured in current animal models.

PMID- 30193705
TI  - Oxytocin and Rodent Models of Addiction.
AB  - Interest for the use of oxytocin as a treatment for addiction began over 40years
      ago. Better known for its roles in parturition, lactation and pair bonding,
      oxytocin also has anxiolytic properties, reduces immune and inflammatory
      responses, and has a role in learning and memory. In this chapter, oxytocin
      effects on addiction processes are described by highlighting research findings
      that have used oxytocin within current preclinical animal models of addiction,
      relapse, or craving. First, we provide a brief background of the endogenous
      oxytocin system followed by descriptions of the behavioral models used to study
      addiction, including models of drug taking and seeking. Then we review recent
      preclinical studies that have used oxytocin as a therapeutic intervention
      throughout multiple stages of the addiction cycle from a behavioral and
      neurobiological perspective. These models encompass the entire range of the
      addiction cycle including acquisition and maintenance of drug taking, withdrawal
      and craving during periods of drug abstinence, and ultimately relapse. We then
      posit several theories about how oxytocin interacts with both drug and social
      reward, as well as presenting a mechanistic account of how specific oxytocin
      receptor localization may contribute to oxytocin's efficacy as an addiction
      therapeutic.

PMID- 30193706
TI  - Effects of Sexual Experience on Psychostimulant- and Opiate-Induced Behavior and
      Neural Plasticity in the Mesocorticolimbic Pathway.
AB  - Many factors, including social elements, influence drug addiction in humans and
      can be modeled in laboratory rodents. In general, the presence of social reward
      is protective against drug abuse and the absence or removal of social reward in
      both humans and rodents increases vulnerability to drug addiction. The current
      review chapter is focused on studies from our lab that have examined the effects
      of sociosexual behavior in male rats on drug-induced behaviors, including changes
      in both psychostimulant and opiate behavior. Furthermore, we review the
      underlying neural mechanisms by which these effects occur. Together, these
      results may help elucidate the neural mechanisms underlying the interaction
      between social and drug rewards and the mechanisms by which a loss of social
      rewards increase the vulnerability to drug addiction development.

PMID- 30193708
TI  - Assessing Social Alcohol Drinking in Rodent Models: Are We There Yet?
AB  - Pathological and social consequences associated with excessive alcohol
      consumption and dependence constitute a serious concern for human well-being. The
      success of preventative and therapeutic strategies for alcohol use disorder
      depends on the development of appropriate animal models of alcohol consumption.
      Alcohol consumption in humans typically occurs in social settings. In contrast,
      the vast majority of animal models investigate alcohol drinking in socially
      isolated animals. A number of rodent model studies have attempted to assess
      drinking of individual animals within social setting. These studies identified
      varied directions of effects of social environment on alcohol consumption.
      However, the interpretation of these results is strongly hampered by technical
      issues associated with the existing approaches to assess drinking of individual
      animals within each group. This review analyzes the existing literature mostly
      focusing on the interpretation caveats of performed studies and highlights some
      of the new directions in these studies.

PMID- 30193707
TI  - Social Defeat Stress, Sex, and Addiction-Like Behaviors.
AB  - Social confrontation is a form of social interaction in animals where two
      conspecific individuals confront each other in dispute over territory, during the
      formation of hierarchies, and during breeding seasons. Typically, a social
      confrontation involves a prevailing individual and a yielding individual. The
      prevailing individual often exhibits aggressive postures and launches attacks,
      whereas the yielding individual often adopts postures of defeat. The yielding or
      defeated animals experience a phenomenon known as social defeat stress, in which
      they show exaggerated stress as well as autonomic and endocrine responses that
      cause impairment of both the brain and body. In laboratory settings, one can
      reliably generate social defeat stress by allowing a naive (or already defeated)
      animal to intrude into a home cage in which its resident has already established
      a territory or is nursing. This resident-intruder paradigm has been widely used
      in both males and females to study mechanisms in the brain that underlie the
      stress responses. Stress has profound effects on drug reward for cocaine,
      methamphetamine, alcohol, and opioids. Particularly, previous experiences with
      social defeat can exaggerate subsequent addiction-like behaviors. The extent of
      these addiction-like behaviors depends on the intensity, duration, frequency, and
      intermittency of the confrontation episodes. This chapter describes four types of
      social defeat stress: acute, repeated, intermittent, and chronic. Specifically,
      it focuses on social defeat stress models used in laboratories to study
      individual, sex, and animal strain differences in addiction-like behaviors.

PMID- 30193709
TI  - Social Factors in Ethanol Sensitization.
AB  - Behavioral sensitization is a neuroadaptive process characterized by an increase
      in a particular behavior after repeated exposure to drugs or other stimuli, such
      as stress. Sensitization can also be extended to neurochemical and neuroendocrine
      sensitization. Several factors can influence sensitization to the effects of
      ethanol. For instance, stress is an important component in addiction that can
      strengthen ethanol-induced behaviors. In animal models, stressful situations can
      be induced by alterations in social aspects of the animal's environment, such as
      maternal separation, social conflicts, and housing conditions. Social conflict
      models involve acute, chronic or intermittent interaction of an animal to a
      conspecific and can occur at any stage of life, including preweaning, adolescence
      or adulthood. These events can influence ethanol-induced behavioral sensitization
      in different ways, such as increases in locomotion, drug reward, and drug-taking
      behaviors. On the other hand, environmental enrichment can produce a protective
      phenotype against drug-related behaviors. In this chapter, we discuss findings
      regarding consequences of social stress and environmental enrichment on
      sensitization to ethanol.

PMID- 30193710
TI  - Social Influences in Animal Models of Opiate Addiction.
AB  - Opiate addiction has reached an epidemic prevalence in recent years, yet social
      influences on the use and abuse of opiates has been widely understudied. In
      particular, the neurobiological substrates of opiate addiction and their
      modulation by social influences are largely unknown, perhaps due to the lack of
      widespread incorporation of social variables into animal models of opiate
      addiction. As reviewed here, animal models such as oral and intravenous drug self
      administration, conditioned place preference, behavioral sensitization, and the
      effects of various stressors, have been useful in identifying some of the
      neurochemical circuitry that mediate social influences on opiate addiction.
      However, it is clear from our review that newer paradigms that incorporate
      various social elements are greatly needed to provide more translational insights
      into the neurobiological basis of opiate addiction. These elements include social
      and environmental enrichment, presence of conspecifics, and procedures that
      require subjects to exert effort to engage in prosocial behavior. A wider
      implementation of social variables into animal models of opiate addiction will
      help inform neurobehavioral strategies to increase the efficacy of treatment.

PMID- 30193711
TI  - Preface.

PMID- 30193712
TI  - High levels of unmet need for family planning in Nepal.
AB  - BACKGROUND: Providing access to family planning services is a basic component and
      a cost-effective intervention to reduce maternal mortality worldwide. It is
      closely linked to women's decision-making power and female emancipation. Unmet
      need for family planning is thus an indicator going beyond maternal health with
      far reaching societal implications. This study examines the level of unmet need
      for family planning in Nepal and its distribution along structural determinants.
      METHODS: Data from the Multiple Indicator Cluster Survey 2014 was utilized for
      analysis. Prevalence of unmet need for family planning was calculated and
      logistic regression models used to ascertain inequity. RESULTS: A total unmet
      need for family planning of 40.9% among the 10,688 included women was observed.
      No major differences between socioeconomic groups could be detected, except for a
      somewhat higher rate of unmet need among the least educated. Total fertility rate
      among the women included was 2.59. Contraceptive use among adolescents was
      alarmingly low, with almost none reporting using any type of contraception.
      CONCLUSION: The lack of major inequity implies that the high level of unmet need
      for contraception is a general problem in society and must be addressed broadly.
      A special focus on education and provision for adolescents is needed in Nepal.

PMID- 30193713
TI  - Women's experiences of contraceptive counselling in the context of an abortion -
      An interview study.
AB  - OBJECTIVE: To identify and understand women's lived experiences of contraceptive
      counselling given at the same time as abortion counselling. METHODS: We
      interviewed 13 women aged 20-39 who had experienced an abortion and the related
      counselling. The women were recruited from five hospitals in Sweden. Interviews
      were analysed using an interpretative phenomenological approach. RESULTS: We
      identified two themes: need for respectful counselling and needs for guidance and
      access to contraceptives. The essence "Being in a state of limbo and feeling
      sceptical" was coalesced from the themes. The women described a state of limbo,
      as being caught in an unwanted and emotionally charged situation. They reported
      that respectful counselling and meeting a skilled health professional helped to
      dispel their scepticism and influenced their plans for contraceptive use post
      abortion. Furthermore, women who wanted an intrauterine device described
      difficulties in access post abortion. CONCLUSION: The women seem to have a
      limited receptivity to contraceptive counselling when they have an unwanted
      pregnancy and are sceptical about contraceptives. Women, who experience respect
      in the counselling, report being helped in contraceptive decision-making. To
      receive respectful counselling and to have good access to intrauterine devices
      emerged as central needs among women at the time of an abortion.

PMID- 30193714
TI  - Perceptions of adolescents and teachers on school-based sexuality education in
      rural primary schools in Uganda.
AB  - BACKGROUND: Evidence-based sexuality education programmes are a cornerstone in
      reducing adolescent sexual risk behaviours and promoting sexual health. Several
      initiatives aimed at reducing sexual and reproductive problems among adolescents
      have been done. These initiatives include life skill education and abstinence
      program. Despite these initiatives teen pregnancy, sexually transmitted diseases
      and abortion are still common among school going adolescents. OBJECTIVES: The
      purpose of this study was to explore the experiences and perceptions of
      adolescents and teachers regarding school-based sexuality education in rural
      primary schools. METHODS: A purposive sample was drawn from primary school-going
      adolescents aged 12-16 years and teachers aged 28-52 in four rural schools.
      Eleven audio taped individual interviews and eight focus group discussions were
      used to collect data. A constant comparison method of data analysis was applied
      by following the Strauss and Corbin (1998) analysis process of open, axial and
      selective coding to analyse textual qualitative data until themes, categories and
      sub-categories were identified and developed. RESULTS: Data analysis revealed
      that adolescents benefitted from School Based Sexuality Education but the
      implementation of programmes was undermined by physical and contextual factors
      such as challenges at national, institutional, community, family and individual
      levels. CONCLUSION: It is vital to review the teaching and learning resources and
      to fully integrate sexuality education into the formal school curriculum. A
      combined effort of major stakeholders including teachers, community leaders,
      adolescents, healthcare professionals and parents is needed for sexuality
      education among adolescents to succeed.

PMID- 30193715
TI  - STI-protective self-efficacy and binge drinking in a sample of university
      students in the United Kingdom.
AB  - OBJECTIVE: Alcohol use has consistently been shown to be related to sexual risk
      taking behaviours. To assess what factors may contribute to the sexual risk
      decision-making process, this study examined the relationships among alcohol use
      (frequency, quantity, and binge drinking), cognitive appraisals of sexual risk
      taking, sex-related alcohol expectancies, and STI-protective self-efficacy.
      METHOD: 138 sexually-active university students who drink alcohol completed
      scales measuring alcohol consumption, appraisals of consequences, sex-related
      alcohol expectancies, and items regarding STI-protective self-efficacy. RESULTS:
      Increasing levels of binge drinking were negatively associated with STI
      protective self-efficacy. A moderated mediation analysis revealed that for binge
      drinkers, stronger appraisals of the positive consequences for having sexual
      intercourse while intoxicated predicted lower STI-protective self-efficacy
      indirectly through increasing rates of sex-related alcohol risk expectancies.
      CONCLUSION: Findings provide evidence of a need to target binge drinkers and
      increase their STI-protective self-efficacy by shifting their focus from positive
      consequences to negative risk consequences of engaging in sexual intercourse
      while intoxicated.

PMID- 30193716
TI  - 'Do you know how to use a condom?' - UK nurse practitioners' conversation about
      men and family planning.
AB  - INTRODUCTION: Health professionals have been identified as central to encouraging
      men to take an active part in family planning. The aim of this article is to
      understand nurse practitioners' conversations about men as family planning
      patients. METHODS: One-to-one, semi-structured interviews were conducted with
      five nurse practitioners. Nurses interviewed worked in a northern UK student
      medical practice serving over 34,000 students with a diverse range of ages and
      demographic backgrounds (both home and overseas students). The research method
      was qualitative using discourse analysis. RESULTS: After completing the analysis,
      two discourses emerged. Discourse one, family planning services are culturally
      female centric, and discourse two, condom use by male family planning patients is
      problematic. DISCUSSION: Implications for how nurse practitioners can continue to
      play an important part when providing care to male family planning patients is
      discussed, specifically in relation to culture and condom efficacy.

PMID- 30193717
TI  - Social media as social support in pregnancy and the postpartum.
AB  - Based on the rapidly growing use of social media and its influence on society an
      online survey to explore social media use and perceptions of social support was
      developed. A survey link or QR, quick read code was provided to new mothers in
      the postpartum setting of an academic medical center, posted on the hospital
      hosted website for new mothers and shared with Centering Pregnancy groups at the
      research hospital. The survey link was available for 4 weeks and 117 mothers from
      64 different zip codes across the United States completed the survey. The
      majority of respondents indicated the main source of social support came from
      their current partner (92%). In addition, 43% used blogs to communicate with
      other mothers, 99% used the internet for answers to parenting questions, 89% used
      social media sites for questions and advice related to pregnancy and/or their
      role as a parent, and 84% considered social media friends a form of social
      support. These results demonstrate social media plays a substantial role in the
      lives of mothers today. Providers of healthcare should become familiar and
      comfortable with social media resources to support mothers of young children.

PMID- 30193718
TI  - New parents' experience of information and sense of security related to postnatal
      care: A systematic review.
AB  - BACKGROUND: Becoming a parent is often a tumultuous experience and a great
      challenge. The transition when a child is born is described affecting the parents
      and their relationship psychically, physically, mentally and emotionally.
      Information within care should be relevant and supportive. Furthermore
      information within the context of care should be relevant, supportive and helpful
      to parents in handling their new situation and increasing their self-reliance.
      AIM: To provide a contextualised understanding of how parents experience
      postnatal care in relation to information and sense of security". METHOD: A
      systematic search was undertaken at PubMed and CINAHL database for literature
      published between January 2002 and August 2017. Inclusion criteria focused on
      postnatal care. Eight of the studies used qualitative methods and two of the
      studies used quantitative methods, as a result the findings could not be combined
      using meta-analysis or meta-synthesis, instead narrative synthesis of the
      findings were used. RESULTS: Ten studies were included. The analysis revealed
      three categories related to parent's experience of information and sense of
      security during the postnatal period. These categories were; Expectations on the
      care; Own resources; and Confirmation. Support from staff and family is described
      as significant for the parents' sense of security. During the first postnatal
      week, the emotions were characterized by anxiety and/or fear. Parents prefer a
      "non-judgmental" attitude from the staff and to be met as an individual.
      CONCLUSION: Family -centred care such as continuity, participation, individually
      adaptation, consistent, information and preparation for parenting appear to be
      important components for parents' sense of security in postnatal care.

PMID- 30193719
TI  - First-time mothers' confidence mood and stress in the first months postpartum. A
      cohort study.
AB  - OBJECTIVES: The aims were to describe first-time mothers' confidence, mood and
      stress 2 and 6 months postpartum and to investigate the extent to which the tools
      measuring maternal confidence and maternal mood used alone or together at 2
      months postpartum predict first-time maternal confidence, mood and stress 6
      months postpartum. DESIGN: A cohort including 513 first-time mothers' self
      reported questionnaires concerning three scales: The Karitane Parenting
      Confidence Scale (KPCS), the Edinburgh Postnatal Depression Scale (EPDS), and the
      Parental Stress Scale (PSS) collected 2 and 6 months postpartum. Descriptive
      statistic, simple and multiple linear regression analysis were used. RESULTS:
      First-time mothers' with confidence scores below the clinical cut-off (KPCS <40)
      fell significantly from 25% to 14% (p < 0.001), symptoms of depression above the
      clinical cut-off (EPDS >= 8) fell significantly from 16% to 12% (p < 0.001), and
      parental stress as a mother fell significantly from a mean of 32.88 to 30.98 (p <
      0.001). The KPCS assessed at 2 months postpartum was the strongest predictor for
      both maternal confidence (R2 = 0.38) and parental stress (R2 = 0.26) 6 months
      postpartum. CONCLUSION: The results support the assumption that parenthood is a
      complicated period for first-time mothers characterised by low confidence,
      symptoms of depression and high stress which improve over time for the majority
      of mothers. The KPCS at 2 months postpartum was the strongest predictor of the
      measures used. Further research is needed to identify parents who are struggling,
      especially for health professionals' whose role is to support parents in their
      parenthood the first period after birth.

PMID- 30193720
TI  - Prescription pattern and trend of oral contraceptives in Japan: A descriptive
      study based on pharmacy claims data (2006 - 2014).
AB  - OBJECTIVE: The use of combined oral contraceptives (COC) as a contraceptive
      method is still limited in Japan, used only by 1.1% of women of reproductive age.
      The usage pattern of COC, such as continuation and preparation switch, between
      COC generations was investigated using large datasets. METHODS: This descriptive
      study spanning from 2006 to 2014 used nationwide prescriptions based on
      administrative databases, including both reimbursed and non-reimbursed drugs. All
      the first-time COC users were included as a cohort. Usage patterns considering
      trends, continuation, and switch of COC generations were also investigated.
      RESULTS: Of the 38,123 patients, the overall mean age at initial use of COC was
      32.9 years. Of the first-time users, 51.2%, 23.7%, 5.6%, and 19.5% received first
      , second-, third-, and fourth-generation COCs, respectively. The overall rate of
      continuation was 59.1%, and the rate of first-time use with switching to other
      generations within 180 days was 3.1%. CONCLUSION: We revealed the actual usage of
      COC in Japan with frequent prescriptions of first- or fourth-generation COCs and
      relatively high age at initial use. Moreover, the COC continuation rate was low,
      and switch was limited. Further studies into its proper usage are recommended.

PMID- 30193721
TI  - Quality of couple relationship among first-time mothers and partners, during
      pregnancy and the first six months of parenthood.

PMID- 30193722
TI  - Effects of a gestational weight gain restriction program for obese women: Sibling
      pairs' weight development during the first five years of life.
AB  - OBJECTIVES: Successful gestational weight gain (GWG) restriction programs for
      obese (Body Mass Index (BMI) >= 30 kg/m2) pregnant women, have not, so far, shown
      convincing effects on infant's weight development. An intervention starting
      during the pregnancy might be too late and a pre-conceptional life style change
      may be preferable. Thus, the aim of this study was to follow children born to
      mothers who had participated in a weight gain restriction program during
      pregnancy, and make comparisons with their younger siblings. STUDY DESIGN AND
      MAIN OUTCOME MEASURES: An extended analysis of 262 children belonging to an
      intervention group and a control group. The effects of BMI at five years of age
      and weight-for-length/height development from two months of age until five years
      of age were assessed. RESULTS: In the intervention group there was a difference
      in BMI at five years of age, between index boys and their younger sisters (p =
      0.016). Mean BMI was lower among the boys compared with their younger female
      siblings. Regarding maternal GWG or the Swedish national reference data there was
      no difference between the index children and their younger siblings within the
      intervention or control groups or between younger siblings in the two groups.
      CONCLUSIONS: Maternal pre-conceptional lifestyle change may have a positive
      effect on the child's weight development during the five first years of age.
      However, the effect of participation in an extensive GWG restriction program when
      it comes to the impact on the offspring's weight development is still unclear and
      further research is required.

PMID- 30193723
TI  - Relationship between intimate partner violence and antiretroviral adherence and
      viral suppression in pregnancy.
AB  - OBJECTIVE: To determine whether intimate partner violence (IPV) during pregnancy
      is associated with increased risk of clinical factors that influence maternal to
      child transmission (MTCT) of HIV. STUDY DESIGN: Retrospective cohort study of
      pregnant women living with HIV (WLHIV) who received prenatal care in a
      multidisciplinary perinatal HIV clinic (2007-2014). All women were assessed for
      IPV status during pregnancy by a social worker and/or health psychologist.
      Records were abstracted for obstetric information and factors associated with
      MTCT of HIV, including antenatal visit attendance, adherence to antiretroviral
      regimen, time until viral suppression after initiation of antiretroviral
      medications, HIV RNA at 36 weeks and at delivery, and preterm birth. Women who
      reported IPV were compared to those who did not using bivariable and
      multivariable logistic and linear regression analyses. RESULTS: Of 215 women
      receiving care during the study period, 91.6% (N = 197) had documentation of IPV
      history. Of these women, 13.7% (N = 27) reported experiencing IPV during
      pregnancy. Women who reported IPV were less likely to be completely adherent to
      antiretroviral doses (38.5% vs. 62.0%, p = 0.039) and required significantly more
      time to achieve stable virologic suppression (16.0 vs. 8.5 weeks, p = 0.010).
      Time to achieve suppression remained significant in multivariable models (beta
      4.68, 95% CI 0.03-9.32). CONCLUSION: IPV during a pregnancy complicated by HIV
      appears to be associated with decreased antiretroviral adherence. Pregnant WLHIV
      who reported IPV exhibited delays in achieving virologic suppression. These women
      represent a vulnerable population who may require additional support and
      interventions to reduce the risk of MTCT of HIV.

PMID- 30193724
TI  - Early secondary repair of labial tears, 1st and 2nd degree perineal lacerations
      and mediolateral episiotomies in a midwifery-led clinic. A retrospective
      evaluation of cases based on photo documentation.
AB  - OBJECTIVES: To examine whether early secondary repair of labial tears, 1st and
      2nd degree perineal lacerations and episiotomies provided an anatomically
      acceptable result. STUDY DESIGN: A retrospective analysis of 126 women undergoing
      an early secondary repair of birth lacerations not involving the sphincter
      complex within 21 days postpartum. Patients were included from 1 January 2014 to
      11 August 2017 at Aarhus University Hospital, Denmark. Photo documentation of the
      wound was available just before the early secondary repair and at the follow-up
      visit after the repair. Photos were evaluated by two trained Urogynaecological
      Consultants. MAIN OUTCOME MEASURES: Whether the anatomic result of the early
      secondary repair was acceptable based on photo documentation. RESULTS: Early
      secondary repair was performed by a specialised team of midwives in 94.4% and by
      doctors in 5.6% of the cases. In all, 72.2% were 2nd degree perineal lacerations.
      The most common indications for early secondary repair were wound dehiscence
      (55.3%) and suboptimal primary repair (34.1%). At the follow-up clinical
      examination seven days after the early secondary repair, the result was
      considered anatomically acceptable in 67.5% of the cases, not optimal in 22.2%
      and not possible to evaluate in 10.3% of the cases. In 7.9% of the cases, wound
      infection was suspected after the early secondary repair. CONCLUSIONS: Based on
      photo documentation, early secondary repair of birth lacerations not involving
      the sphincter complex provides an anatomically acceptable result in the majority
      of cases without risk of serious complications.

PMID- 30193725
TI  - Socio-demographic factors affecting the choice of place of childbirth among
      migrant and native women - A case control study from Chandigarh, India.
AB  - OBJECTIVE: India is one of the countries with high maternal mortality ratio. Home
      deliveries persist despite various initiatives, including cash incentives, to
      promote hospital birth. This study aims to compare the profile of women who
      deliver at home and those who deliver at institutions with a special focus on
      migration status. METHODS: A list of all women who delivered between January to
      December 2012 was obtained from the antenatal register of a polyclinic in
      Chandigarh, India. An unmatched case control study design was used to compare the
      profile of women who delivered at home and women who delivered in an institution.
      RESULTS: Of 219 women studied, 57 (26%) had delivered at home. Our study
      identified being a migrant, having lower family income, living in slums,
      illiteracy of mother, early age at marriage, higher parity and no previous
      childbirth in an institution as factors favoring home delivery. Ninety three
      percent of home deliveries were among women who had migrated into Chandigarh from
      other states. The significant association between migration status and home
      delivery (Odds ratio (OR) = 3.262, p = 0.026) ceased to exist after adjusting for
      education (OR = 1.699, p = 0.367) and income (OR = 2.277, p = 0.152). CONCLUSION
      AND CLINICAL IMPLICATION: Most home deliveries had occurred among migrant women.
      Health-related choices of the migrants apparently reflect the influence of other
      social determinants of health like education and income. Mainstreaming of the
      health efforts addressing the complex web of social determinants intertwined with
      the process of migration is the need of the hour.

PMID- 30193727
TI  - Challenges in providing quality care for women with female genital cutting in
      Sweden - A literature review.
AB  - Due to migration, health care needs in relation to female genital cutting (FGC)
      are increasingly emerging in European health care contexts, with Sweden being no
      exception. Recent estimates suggest that up to 38 000 girls and women with some
      form of FGC are living in Sweden, the majority from Somalia. Despite receiving
      high numbers of immigrants from FGC practising countries, health care services in
      many European countries seem largely unprepared in caring for circumcised
      patients. This literature review aims to identify challenges involved in
      providing quality care for circumcised women in Sweden. Two themes were
      identified; lacking technical skills and communication problems and ethnocentric
      attitudes. Lacking technical skills involved midwives and gynaecologists feeling
      insecure in how to technically deal with infibulated women during childbirth,
      something that often resulted in ad hoc solutions and improvisation. They related
      this insecurity to a lack of theoretical and practical training of FGC related
      health problems. In communication problems and ethnocentric attitudes both health
      care professionals and circumcised women reported facing difficulties in
      communicating about FGC, largely due to language barriers and perceived
      sensitivity of the issue. In conclusion, skills among health care professionals
      in Sweden caring for circumcised patients could be strengthened. This should be
      taken into consideration when planning midwifery and gynaecology curricula, and
      in providing in-service training for health care professionals likely to meet
      circumcised women in their practice.

PMID- 30193726
TI  - Perfectionistic traits and importance given to parenthood are associated with
      infertility-related quality of life in a sample of infertile women with and
      without endometriosis.
AB  - OBJECTIVE: To assess quality of life and psychological differences between
      infertile women with endometriosis and without endometriosis. To investigate
      predictive role of perfectionism, mindful awareness and beliefs about parenthood
      to quality of life in a sample of women with fertility problems. METHODS: 43
      infertile women (22 with endometriosis; 21 without endometriosis) who recurred to
      Assisted Reproductive Treatments (ARTs) in the last 12 months took part to this
      cross-sectional study. Sociodemographic and clinical data were collected by means
      of a structured ad hoc questionnaire. Fertility Quality of Life, Fertility
      Problem Inventory - Need of parenthood subscale, Obsessive Beliefs Questionnaire 
      Perfectionism subscale, and Cognitive and Affective Mindfulness Scale - Revised
      were used to assess target outcomes. RESULTS: Any difference in quality of life
      and psychological condition was found between infertile women with and without
      endometriosis. Importance given to parenthood (beta = -.60, p < .001) and
      perfectionism (beta = -.30, p < .05) predicted quality of life related to
      fertility issues, independently of group. CONCLUSIONS: Infertility might elicit
      self-discrepancy between real-self (i.e. being infertile) and ideal-self (being
      fertile), which in turn has a negative impact on quality of life. Conclusions
      about the role of psychologist in ART's team are discussed.

PMID- 30193729
TI  - Editorial.

PMID- 30193728
TI  - Living with painful endometriosis - A struggle for coherence. A qualitative
      study.
AB  - OBJECTIVES: The study sought to examine women's experience of painful
      endometriosis including long-term aspects, social consequences, impact of
      treatment and development of own coping strategies. STUDY DESIGN: This
      qualitative study was based on 16 individual interviews analyzed according to
      grounded theory. The thirteen women (age 24-48) were recruited at a pain clinic
      in Stockholm, Sweden. RESULTS: A theory illustrating women's experience of living
      with painful endometriosis was developed with three categories and one core
      category. Bidirectional interactions between the categories and with the core
      category were found. Endometriosis influenced the women's sensations, feelings
      and reactions, creating a sense of difference from other women (category: Woman
      with painful endometriosis). The condition led to either helpful or harmful
      encounters with health care and significant others (category: Dependence). It
      also had overall physical, social and existential consequences (category: A
      ruined life). To cope, the women had to struggle for coherence by searching for
      understanding, coping and meaning (core category: Living with painful
      endometriosis). CONCLUSIONS: Living with severe painful endometriosis signified a
      struggle for coherence. The women needed to deal with feelings of difference,
      dependence and a ruined life and thus struggled for understanding, coping and
      meaning. Health-care providers should promote the struggle for coherence by
      explaining the feeling of difference, minimizing dependence and supporting the
      process of disease-related grief.

PMID- 30193730
TI  - Contrast Enhanced Ultrasound (CEUS) Is Not Able to Identify Vulnerable Plaques in
      Asymptomatic Carotid Atherosclerotic Disease.
AB  - OBJECTIVES: Contrast enhanced ultrasound (CEUS) has been suggested as an imaging
      tool for detection of asymptomatic carotid atherosclerotic disease (ACAD) at high
      risk of cerebral embolisation. The objective of this study was to evaluate CEUS
      and immunohistochemical (IHC) patterns in ACAD (i.e., without any neurologic
      symptoms in the last 6 months) and their correlations with histology. METHODS:
      CEUS analysis was classified on a semiquantitative basis using a three-point
      classification scale. Plaque morphology was assessed using the American Heart
      Association (AHA) classification of atherosclerotic plaques, then accordingly
      assigned as non-vulnerable (AHA Type IV/V) or vulnerable (AHA Type VI). IHC
      analysis for intra-plaque neo-angiogenesis (IPN) was identified by CD34/VEGF
      immunostaining and classified on a semiquantitative basis using a four-point
      classification scale. Both CEUS and IHC analyses were performed and scored by
      single observers. RESULTS: Fifty-eight consecutive asymptomatic patients (mean
      age 73 years, 33 males) undergoing carotid endarterectomy were included in the
      final analysis. Nineteen had AHA Class IV/V plaques, and the remaining 39 had AHA
      Class VI plaques. There were two main findings of the study: (a) histologically
      proven vulnerable plaques compared with histologically proven non-vulnerable
      plaques had denser IPN (p = .004), but did not show more pronounced contrast
      enhancement; (b) the correlation between IHC analysis and CEUS analysis was
      significant for both vulnerable and non-vulnerable plaques (p = .04 and p = .01,
      respectively), but it was direct for AHA Type IV/V plaques and inverse for AHA
      Type VI plaques. CONCLUSIONS: The main findings of the study were that
      histologically proven vulnerable plaques (i.e., AHA Class VI) as compared with
      histologically proven non-vulnerable plaques (i.e., AHA Class IV/V) had denser
      neo-vascularisation, but not more pronounced contrast enhancement.

PMID- 30193731
TI  - Aortic Puncture Through Sewn-on Graft for TEVAR and Aortic Bypass.

PMID- 30193732
TI  - Knockdown of long non-coding RNA TP73-AS1 suppresses triple negative breast
      cancer cell vasculogenic mimicry by targeting miR-490-3p/TWIST1 axis.
AB  - Triple negative breast cancer (TNBC) is among the most clinically aggressive
      subtypes of breast cancer. Despite the availability of new drugs, patients
      suffering TNBC bear disheartening prognosis. Vasculogenic mimicry (VM) is a
      malignant tumor specific non-endothelial vascular network, which provide oxygen
      and nutrients to tumor cells and facilitate tumor progression. Therefore
      targeting TNBC VM formation may contribute to tumor treatment. In this study, we
      found that long non-coding RNA TP73 antisense RNA 1 (TP73-AS1) was upregulated in
      VM positive TNBC tissues. Knockdown of TP73-AS1 suppressed TNBC cell line MDA-MB
      231 cell VM formation in vitro. In addition, RNA immunoprecipitation assay and
      dual luciferase reporter assay showed that TP73-AS1 bound to miR-490-3p in a
      sequence-specific manner. miR-490-3p was downregulated in VM positive tissues and
      was involved in TP73-AS1-mediated MDA-MB-231 cell VM formation. Furthermore,
      TWIST1 was a target of miR-490-3p and participated in TP73-AS1/miR-490-3p
      modulated MDA-MB-231 cell VM formation. Findings in this study may provide
      insight in TNBC management.

PMID- 30193733
TI  - Ploidy-dependent change in cyclin D2 expression and sensitization to cdk4/6
      inhibition in human somatic haploid cells.
AB  - Near-haploidy is observed in certain cancer types, but ploidy-dependent
      alterations in gene regulation in the haploid state remain elusive. Here, by
      comparative transcriptome analysis between human isogenic haploid and diploid
      cell lines, we found lowering of cyclin D2 level in haploids. Acute genome
      duplication in haploids restored cyclin D2 expression to diploid level,
      indicating that the regulation of cyclin D2 expression is directly linked to
      ploidy. Downstream pathways of cyclin D2, such as Rb phosphorylation and p27
      sequestration remained intact in haploids, suggesting that they adapt to lowered
      cyclin D level. Interestingly, however, haploid cells were more susceptible to
      cdk4/6 inhibition compared to diploids. Our finding indicates feasibility of
      selective growth suppression of haploid cells based on ploidy-linked gene
      regulation.

PMID- 30193735
TI  - An insufficient number of examined lymph nodes may offset the survival benefit
      from neoadjuvant therapy in esophageal squamous cell carcinoma.

PMID- 30193734
TI  - Grhl2 regulation of SPINT1 expression controls salivary gland development.
AB  - Development of the salivary gland is characterized by extensive branching
      morphogenesis and lumen formation, the latter of which is closely associated with
      differentiation into acinar and ductal cells. Although various molecules,
      including signaling and cell adhesion molecules, have been implicated in salivary
      gland development, transcription factors (TFs) regulating the expression of those
      molecules and morphological development of the gland are largely unknown. Here we
      show that knockdown of the epithelial TF, Grainyhead-like 2 (Grhl2), with siRNA
      in developing mouse submandibular salivary gland (SMG) cultured ex vivo resulted
      in retardation of epithelial development. This retardation was concomitant with
      suppression of gene expression for the cell adhesion molecules, such as E
      cadherin and the extracellular protease inhibitor SPINT1, and with the
      disorganized deposition of the basal lamina protein laminin. ChIP-PCR
      demonstrated the binding of Grhl2 protein to the Spint1 gene in the SMG. Notably,
      addition of recombinant SPINT1 protein in cultured SMG overcame the suppressive
      effects of Grhl2 siRNA on epithelial development and laminin deposition. These
      findings show that Grhl2 regulation of SPINT1 expression controls salivary gland
      development.

PMID- 30193737
TI  - Differential Ion Mobility-Mass Spectrometry for Detailed Analysis of the
      Proteome.
AB  - The field of proteomics is increasingly concerned with the diversity and
      functional relevance of protein modifications. Differential ion mobility
      spectrometry (DMS) is emerging as a tool to detect and quantify additional
      peptide and protein species that are difficult to analyse with conventional
      instrumental methods. In this review, recent advances in DMS are discussed, with
      a focus on the different types of DMS instruments now available to researchers in
      proteomics. Furthermore, the combination of DMS with mass spectrometry (MS) for
      increased proteome coverage and the targeted analysis of modification patterns on
      single proteins is highlighted. Frontier areas of research, such as the analysis
      of intact proteoforms, and future directions for the implementation of DMS in
      proteomics are also discussed.

PMID- 30193736
TI  - Vascular Endothelial Growth Factor Enhances Compensatory Lung Growth in Piglets.
AB  - BACKGROUND: Vascular endothelial growth factor has been found to accelerate
      compensatory lung growth after left pneumonectomy in mice. The aim of this study
      was to determine the natural history and the effects of vascular endothelial
      growth factor on compensatory lung growth in a large animal model. METHODS: To
      determine the natural history of compensatory lung growth, female Yorkshire
      piglets underwent a left pneumonectomy on days of life 10-11. Tissue harvest and
      volume measurement of the right lung were performed at baseline (n = 5) and on
      postoperative days 7 (n = 5), 14 (n = 4), and 21 (n = 5). For pharmacokinetic
      studies, vascular endothelial growth factor was infused via a central venous
      catheter, with plasma vascular endothelial growth factor levels measured at
      various time points. To test the effect of vascular endothelial growth factor on
      compensatory lung growth, 26 female Yorkshire piglets underwent a left
      pneumonectomy followed by daily infusion of vascular endothelial growth factor at
      200 ug/kg or isovolumetric 0.9% NaCl (saline control). Lungs were harvested on
      postoperative day 7 for volume measurement and morphometric analyses. RESULTS:
      Compared with baseline, right lung volume after left pneumonectomy increased by
      factors of 2.1 +/- 0.6, 3.3 +/- 0.6, and 3.6 +/- 0.4 on postoperative days 7, 14,
      and 21, respectively. The half-life of VEGF ranged from 89 to 144 minutes. Lesser
      doses of vascular endothelial growth factor resulted in better tolerance, volume
      of distribution, and clearance. Compared with the control group, piglets treated
      with vascular endothelial growth factor had greater lung volume (P < 0.0001),
      alveolar volume (P = 0.001), septal surface area (P = 0.007) and total alveolar
      count (P = 0.01). CONCLUSION: Vascular endothelial growth factor enhanced
      alveolar growth in neonatal piglets after unilateral pneumonectomy.

PMID- 30193738
TI  - Cost-Saving Opportunities with Appropriate Utilization of Cardiac Telemetry.
AB  - A third of healthcare spending in the United States is considered waste, and
      costs are growing at an unsustainable rate. Reducing unnecessary cardiac
      telemetry, a costly intervention with a high potential for overuse, may be an
      opportunity to reduce waste. We performed a review of 250 consecutive patients
      admitted to telemetry capable beds on the general medical-surgical, noncritical
      care units. Based on the American Heart Association Practice Standards for
      Electrocardiographic Monitoring in Hospital Settings, appropriateness of
      telemetric monitoring during each inpatient day was assessed, with identification
      of significant new arrhythmias, code calls, and clinical decisions resulting from
      telemetry. Cost of a telemetry day was calculated using a time-driven activity
      based cost model. Patients (63 +/- 19 years, 54% male) spent a total of 1,640
      days hospitalized, 1,399 (85%) of which were on telemetry. Average length of stay
      was 6.6 days, and average telemetry time was 5.6 days. Only 334 (24%) telemetry
      days were deemed appropriate based on Practice Standards. During telemetric
      monitoring, 16 new significant arrhythmias were detected, 4 code calls were made,
      and 19 significant clinical decisions were prompted by telemetry. No cardiac code
      call occurred on a nontelemetry day. The cost of telemetry was calculated as
      $34.28 more per day than a nontelemetry hospital day. Elimination of
      inappropriate telemetry days would result in a minimum estimated savings of
      $37,007 in these 250 patients, and an annual savings of $528,241 overall.
      Telemetric monitoring is frequently overused. In conclusion, our findings propose
      that a reduction in inappropriate telemetry days in accordance with the American
      Heart Association Practice Standards could result in significant cost savings.

PMID- 30193739
TI  - Letter to the editor: "Coexistent thyroid nodules in patients with graves'
      disease: What is the frequency and the risk of malignancy?"

PMID- 30193740
TI  - A survey of the practice and attitudes of surgeons regarding the treatment of
      appendicitis.
AB  - BACKGROUND: We surveyed surgeons to document their attitudes, practice, and risk
      tolerance regarding the treatment of appendicitis. METHODS: A web-based survey
      was sent to the EAST membership. The primary composite endpoint was defined as 1
      year incidence of perioperative complications, antibiotic failure, infections, ED
      visits, and readmissions. RESULTS: A total of 563 of 1645 surveys were completed
      (34% response). Mean age was 47 +/- 10 years and 98% were from the United States.
      Most (72%) were employed at academic teaching hospitals and 66% practiced in an
      urban setting. There were significant differences in treatment recommendations
      for different presentations of appendicitis. Regarding the primary composite
      endpoint, surgeons would tolerate a median 17% [10%-25%] excess morbidity in
      order to avoid an operation (i.e. non-inferiority) and would require a median 24%
      [10%-50% lower morbidity for the surgical approach in order to declare it a
      superior treatment (i.e. superiority). CONCLUSIONS: To be considered non
      inferior, antibiotic therapy of appendicitis cannot have >17% excess morbidity
      and appendectomy must have at least 24% lower morbidity to be considered
      superior.

PMID- 30193741
TI  - Concordance of the ions and GAP anion obtained by gasometry vs standard
      laboratory in critical care.
AB  - OBJECTIVE: To evaluate the differences observed in ion and GAP anion
      determinations obtained by point-of-care (POC) blood gas versus laboratory
      biochemical testing, and to analyze the possible errors according to the limits
      of normality. MATERIAL AND METHODS: A descriptive, cross-sectional retrospective
      study was made to assess concordance between two diagnostic tests in patients
      admitted to the Critical Care Unit of Ourense University Hospital Complex
      (Spain), between July and November 2015, involving at least one coinciding
      biochemical test and POC determination. Patients under 18years of age were
      excluded. RESULTS: A total of 1,073 samples were analyzed. Lin's concordance
      correlation coefficients for sodium, potassium and chlorine were 0.87, 0.84 and
      0.72, respectively. Kappa concordance of the normality limits for sodium,
      potassium and chlorine was 0.63, 0.74 and 0.32. The results indicated poor
      correlation of the anion GAP and null concordance between POC and biochemical
      testing, including the value corrected for albumin. CONCLUSIONS: Poor concordance
      was observed between the ion values as determined by biochemistry and blood
      gases; the two methods are therefore not interchangeable. Kappa agreement with
      normality limits was good for sodium and potassium, and weak for chlorine.
      Possible validity was noted in orienting the classification within the ion
      limits, with the exception of chlorine. No agreement was recorded in relation to
      the anion GAP, even that corrected for albumin.

PMID- 30193742
TI  - Clinimetrics: Amyotrophic Lateral Sclerosis Functional Rating Scale-revised
      (ALSFRS-R).

PMID- 30193743
TI  - Clinimetrics: Measuring Yourself Medical Outcome Profile.

PMID- 30193744
TI  - Various Leisure-Time Physical Activities Associated With Widely Divergent Life
      Expectancies: The Copenhagen City Heart Study.
AB  - OBJECTIVE: To evaluate the differential improvements in life expectancy
      associated with participation in various sports. PATIENTS AND METHODS: The
      Copenhagen City Heart Study (CCHS) is a prospective population study that
      included detailed questionnaires regarding participation in different types of
      sports and leisure-time physical activity. The 8577 participants were followed
      for up to 25 years for all-cause mortality from their examination between October
      10, 1991, and September 16, 1994, until March 22, 2017. Relative risks were
      calculated using Cox proportional hazards models with full adjustment for
      confounding variables. RESULTS: Multivariable-adjusted life expectancy gains
      compared with the sedentary group for different sports were as follows: tennis,
      9.7 years; badminton, 6.2 years; soccer, 4.7 years; cycling, 3.7 years; swimming,
      3.4 years; jogging, 3.2 years; calisthenics, 3.1 years; and health club
      activities, 1.5 years. CONCLUSION: Various sports are associated with markedly
      different improvements in life expectancy. Because this is an observational
      study, it remains uncertain whether this relationship is causal. Interestingly,
      the leisure-time sports that inherently involve more social interaction were
      associated with the best longevity-a finding that warrants further investigation.

PMID- 30193745
TI  - The inferior turbinate: An autonomic organ.
AB  - The inferior turbinate has well-recognized respiratory and immune functions to
      provide the airway with appropriate warmth, humidification, and filtration of the
      inspired air while sampling the environment for pathogens. Normal functioning of
      the inferior turbinate relies on an intact autonomic system to maintain
      homeostasis within the nasal cavity. The autonomic nervous system innervates the
      submucosal glands and the vasculature within the inferior turbinate, resulting in
      control of major turbinate functions: nasal secretions, nasal patency, warmth,
      and humidification. This review will summarize the autonomic innervations of the
      turbinates, both the normal and abnormal autonomic processes that contribute to
      the turbinate functions, and the clinical considerations regarding optimal
      functioning of the turbinate autonomic system.

PMID- 30193746
TI  - Forensic thanatology and the pink tooth phenomenon: From the lack of relation
      with the cause of death to a potential evidence of cadaveric decomposition in
      dental autopsies - Case series.
AB  - Forensic thanatology comprises the investigation of every phenomenon related to
      death performed through cadaveric exams. The pink tooth phenomenon (PTP) emerges
      as a thanatological finding registered during medical or dental autopsy. The PTP
      consists of a reddish or pink coloration caused in the teeth by the penetration
      of pulpal hemoglobin in the dentinal tubules. Initially, the PTP was associated
      with specific violent deaths, such as drowning, hanging and poisoning. However,
      scientific reports have pointed towards the occurrence of PTP as an expression of
      cadaveric decomposition regardless of the cause of death. The present study aims
      to report eight dental autopsies of victims of violent death that presented the
      PTP. The autopsies were conducted by forensic pathologists and dentists between
      2013 and 2018. Seven victims were males and one was female. The age ranged above
      6years old. Cranio-encephalic trauma, firearm shooting and asphyxia figured as
      the causes of death. All the victims were in advanced decomposition. The PTP was
      detected in deciduous and permanent, anterior and posterior and maxillary and
      mandibular teeth. Forensic experts, especially dentists, must be aware of the PTP
      for more detailed registration of postmortem findings and more accurate cadaveric
      exams.

PMID- 30193747
TI  - Atrial Fibrillation and Deterioration in Cognitive Function.
AB  - The link between atrial fibrillation and cognitive decline and dementia has
      gained interest of the medical community lately. More research is being conducted
      to prevent and or delay this morbidity as no curative therapy is available for
      cognitive decline and dementia. The exact mechanism of causation is unclear.
      Multiple pathophysiological mechanisms have been implicated. Lately, treatment
      for atrial fibrillation including anticoagulation and catheter ablation therapies
      have shown to decrease the risk of deterioration of cognitive function. In this
      review we summarize epidemiologic studies linking the association, potential
      mechanisms, and impact of various modalities of therapy of atrial fibrillation on
      cognitive function outcomes.

PMID- 30193748
TI  - Health Care Resource Use, Costs, and Diagnosis Patterns in Patients With
      Schizophrenia and Bipolar Disorder: Real-world Evidence From US Claims Databases.
AB  - PURPOSE: Schizophrenia (SCZ) and bipolar disorder (BD) are typically viewed as
      nonconcurrent psychiatric disorders, yet patients may experience mood and SCZ
      symptoms simultaneously. Several studies have shown overlap between SCZ and BD
      symptoms and susceptibility genes. This study explored the following: (1)
      patterns of administrative claims; (2) demographic characteristics and
      comorbidities; (3) health care resource use; and (4) health care costs in
      patients with diagnoses of SCZ, type I BD (BD-I), and both in a real-world
      setting. METHODS: This study was a retrospective cohort trial using 4.5years
      (January 1, 2012-June 30, 2016) of Truven MarketScan commercial, Medicaid, and
      Medicare supplemental databases. We considered a patient to have a new episode of
      SCZ if he or she had 1 inpatient claim or 2 outpatient claims for SCZ within the
      identification period (January 1, 2013-June 30, 2015). BD-I was defined in an
      analogous way. Three study cohorts were defined: (1) SCZ alone (cohort I), met
      the claims-based diagnostic criteria for SCZ; (2) BD-I alone (cohort II), met the
      claims-based diagnostic criteria for BD-I; and (3) BD-I and SCZ (cohort III), met
      the claims-based diagnostic criteria for both SCZ and BD-I. FINDINGS: Of the
      63,725 patients in the final sample, 11.5% (n = 7336) had a new episode of SCZ
      alone (cohort I), 80.8% (n = 51,480) had a new episode of BD-I alone (cohort II),
      and 7.7% (n = 4909) had new episodes of both SCZ and BD-I (cohort III).
      Considering cohort III, 18.8% (n = 927) received both diagnoses on the same day.
      In the year after diagnosis, the cohort having a diagnosis of both SCZ and BD-I
      (cohort III) had the highest all-cause hospitalization rates (67.4% vs 39.5% in
      SCZ alone and 33.7% in BD-I alone) and the highest mean (SD) number of emergency
      department visits (3.44 [7.1] vs 1.39 [3.5] in SCZ alone and 1.29 [3.2] in BD-I
      alone). All-cause total health care costs were highest in the cohort having a
      diagnosis of both SCZ and BD-I (mean [SD]), $51,085 [$62,759]), followed by the
      SCZ alone cohort ($34,204 [$52,995]), and the BD-I alone cohort ($26,396
      [$48,294]). IMPLICATIONS: Our analyses indicate that a substantial number of
      patients received diagnoses of both SCZ and BD-I, based on claims, in a 2.5-year
      period. Patients with a diagnosis of both SCZ and BD-I had higher health care
      utilization and costs than patients with either diagnosis alone. We identified
      differential patient characteristics, utilization of medications and health care
      services, and health care costs among the cohorts.

PMID- 30193749
TI  - Commentary on the Impact of Obesity on PediatricDiabetes.
AB  - While conventionally most children diagnosed with diabetes are thought to have
      type 1 diabetes mellitus (T1DM), with the increased prevalence of obesity, more
      are being affected by type 2 (T2) DM. Obesity leads to increased insulin
      resistance, which over time can lead to progressive beta-cell failure and
      ultimately T2DM. However, patients developing T1DM may also be obese, making both
      the proper classification and management of diabetes in children more
      challenging. In this commentary, the authors discuss the impact ofobesity on the
      presentation of pediatric diabetes, how to differentiate between T1DM and T2DM,
      and the proper management of both diseases.

PMID- 30193750
TI  - Advancement of Feeds in Preterm Low Birth Weight Infants.

PMID- 30193751
TI  - Persistent Hypoglycemia in Children: Targeted Gene Panel Improves the Diagnosis
      of Hypoglycemia Due to Inborn Errors of Metabolism.
AB  - OBJECTIVES: To evaluate the role of next generation sequencing in genetic
      diagnosis of pediatric patients with persistent hypoglycemia. STUDY DESIGN: Sixty
      four patients investigated through an extensive workup were divided in 3
      diagnostic classes based on the likelihood of a genetic diagnosis: (1) single
      candidate gene (9/64); (2) multiple candidate genes (43/64); and (3) no candidate
      gene (12/64). Subsequently, patients were tested through a custom gene panel of
      65 targeted genes, which included 5 disease categories: (1) hyperinsulinemic
      hypoglycemia, (2) fatty acid-oxidation defects and ketogenesis defects, (3)
      ketolysis defects, (4) glycogen storage diseases and other disorders of
      carbohydrate metabolism, and (5) mitochondrial disorders. Molecular data were
      compared with clinical and biochemical data. RESULTS: A proven diagnosis was
      obtained in 78% of patients with suspicion for a single candidate gene, in 49%
      with multiple candidate genes, and in 33% with no candidate gene. The diagnostic
      yield was 48% for hyperinsulinemic hypoglycemia, 66% per fatty acid-oxidation and
      ketogenesis defects, 59% for glycogen storage diseases and other carbohydrate
      disorders, and 67% for mitochondrial disorders. CONCLUSIONS: This approach
      provided a diagnosis in ~50% of patients in whom clinical and laboratory
      evaluation did not allow identification of a single candidate gene and a
      diagnosis was established in 33% of patients belonging to the no candidate gene
      class. Next generation sequencing technique is cost-effective compared with
      Sanger sequencing of multiple genes and represents a powerful tool for the
      diagnosis of inborn errors of metabolism presenting with persistent hypoglycemia.

PMID- 30193752
TI  - Timing of Umbilical Cord Clamping and Infant Brain Development.

PMID- 30193753
TI  - Treatment of adult Graves' disease.
AB  - Treatment strategy in Graves' disease firstly requires recovery of euthyroid
      status by antithyroid therapy. Treatment modalities, precautions, advantages and
      side-effects are to be discussed with the patient. No particular treatment
      modality has demonstrated superiority. Pregnancy or pregnancy project affects
      choice of treatment and monitoring. Graves' orbitopathy is liable to be
      aggravated by iodine-131 treatment and requires pre-treatment assessment. Iodine
      131 treatment aims at achieving hypothyroidism. Thyroid surgery for Graves'
      disease should preferably be performed by an expert team. In case of recurrence
      of hyperthyroidism, the various treatment options should be discussed with the
      patient. Empiric treatment of thyroid dermopathy uses local corticosteroids in
      occlusive dressing.

PMID- 30193754
TI  - The 2018 Surviving Sepsis Campaign's Treatment Bundle: When Guidelines Outpace
      the Evidence Supporting Their Use.

PMID- 30193755
TI  - Corrigendum to "Experimental infection model for Johne's disease using a
      lyophilised, pure culture, seedstock of Mycobacterium avium subspecies
      paratuberculosis" [Veterinary Microbiology 141 (2010) 301-311].

PMID- 30193756
TI  - Is CCR6 Required for the Development of Psoriasiform Dermatitis in Mice?

PMID- 30193757
TI  - IFN-gamma Promotes, but Dexamethasone Dissociates, Toll-Like Receptor 2/1-Induced
      Host Responses in Human Macrophages.

PMID- 30193758
TI  - Management of seborrhoeic keratosis and actinic keratosis with an erbium:YAG
      laser-experience with 547 patients.
AB  - Seborrhoeic keratosis and actinic keratosis are common skin lesions, and the
      latter is a precursor for skin malignancy. The treatment regime can be lesion
      directed or field-directed. Current lesion-directed treatments include
      cryotherapy, shave excision, and laser ablation. Field-directed treatment
      typically encompasses multiple topical agents. This article presents the authors'
      experience of lesion- and field-directed erbium:YAG laser treatment of 547
      patients (Fotona Dualis XS Laser). In this series of patients, those who had
      resurfacing as field therapy showed no recurrence during the 12-month review
      period. However, there were six cases of recurrence in the group who underwent
      lesion-directed treatment over the same period. Furthermore, the results
      illustrated that the incidence of recurrence of actinic keratosis with malignant
      transformation was around 2.5%. The production of p53-negative keratin sites
      after laser ablation acts as a protective environment in the prevention of
      cutaneous malignancies. Thus, laser ablation not only removes lesions and
      resurfaces, but also protects against skin cancer. Therefore, this treatment is
      very welcome, especially in light of the increasing incidence of skin cancers.

PMID- 30193759
TI  - Separating hearing sensitivity from auditory perceptual abnormalities in clinical
      high risk (CHR) youth.

PMID- 30193760
TI  - N400 event-related brain potential evidence for semantic priming deficits in
      persons at clinical high risk for psychosis.

PMID- 30193761
TI  - The Whitmore aphorism.

PMID- 30193762
TI  - Author response to: Modulating kynurenine monooxygenase in microglia: The need
      for further characterization.

PMID- 30193764
TI  - Comment on: Evaluation of low-intensity anti-coagulation with a fully
      magnetically levitated centrifugal-flow circulatory pump-the MAGENTUM 1 study.

PMID- 30193763
TI  - Intraoperative extracorporeal support during lung transplantation in patients
      bridged with venovenous extracorporeal membrane oxygenation.
AB  - BACKGROUND: Venovenous (VV) extracorporeal membrane oxygenation (ECMO) is the
      preferred configuration for bridging respiratory failure patients while awaiting
      lung transplantation. However, there is no consensus on intraoperative
      extracorporeal cardiopulmonary support during lung transplantation in these
      patients. METHODS: The configuration of the intraoperative extracorporeal circuit
      after VV ECMO bridge was reviewed and correlated with clinical outcomes. This
      retrospective cohort study performed at our university hospital included 34
      patients who were successfully bridged solely with VV ECMO to lung
      transplantation during the period 2007 to 2016. Indications to switch to
      intraoperative venoarterial (VA) ECMO were hemodynamic compromise (systemic
      hypotension or mean pulmonary artery pressure >40 mm Hg) or when this scenario
      was thought to be highly likely. RESULTS: The median duration of bridging was 12
      (IQR 7 to 19) days. Intraoperatively, 3 patients (8.8%) required cardiopulmonary
      bypass. Twenty patients (58.8%) stayed on VV ECMO and 11 (32.3%) were switched to
      central VA ECMO. Between the 2 types of intraoperative ECMO (VV vs VA), there
      were no significant differences in post-operative ECMO duration, chest reopening
      for bleeding, or renal replacement therapy. There was no significant difference
      in 90-day mortality (0% and 9.0%, p = 0.35) or in long-term survival (p = 0.59).
      The intraoperative transfusion of red blood cells tended to be higher in the VA
      group (5 [4 to 9] vs 8 [6 to 13] units, p = 0.06). Use of intraoperative VA ECMO
      was associated with the use of low-flow VV device bridging and lobar
      transplantation. CONCLUSIONS: Using the existing VV ECMO bridge intraoperatively
      during lung transplantation is feasible and provides comparable outcomes to
      patients converted to central VA ECMO for compromised hemodynamics.

PMID- 30193765
TI  - Niche shift in three foraging insectivorous birds in lowland Malaysian forest
      patches.
AB  - With the rapid growth of agricultural areas globally, forest birds increasingly
      encounter fragmented landscapes in which forest patches are surrounded by an
      agricultural plantation matrix, yet how birds respond behaviourally to this
      fragmentation is poorly understood. Information on microhabitat requirements of
      birds is scarce, but nevertheless essential to predicting adaptation of bird
      species to the patchy landscapes. We investigated foraging patterns of three
      tropical insectivorous birds, Green Iora Aegithina viridissima, Pin-striped Tit
      Babbler Macronus gularis and Chestnut-winged Babbler Cyanoderma erythropterum, to
      determine whether they vary in foraging methods in different forest patches. Our
      study area encompassed old-logged lowland forest; one continuous forest and three
      forest patches. Observations were performed for 15 days every month for a period
      of 13 months. Information on foraging height, substrate, attack manoeuvres, and
      foliage density was collected independently for each foraging bird individual.
      All three species used different foraging substrates and attack manoeuvres in
      different habitat types. The Green Iora frequently used lower strata when
      foraging in forest patches as opposed to continuous forest, while the Pin-striped
      Tit-Babbler tended to forage in more dense vegetation in patches. Only Chestnut
      winged Babbler displayed complete foraging plasticity across all study
      parameters. Different habitat features (e.g., edges, microclimates) between
      continuous forest and forest patches significantly influenced the foraging
      strategies of the study species. These changes in foraging strategies suggest
      that some Malaysian forest birds (e.g. generalist species) can respond
      behaviourally to fragmentation and habitat loss. Although continuous forest has
      critically important characteristics that need to be conserved, remnant forest
      patches are also important as ecological movement corridors and foraging grounds
      for birds.

PMID- 30193766
TI  - Trends in the Incidence and Treatment of Benign Vocal Fold Lesions in Korea, 2006
      2015: A Nationwide Population-based Study.
AB  - OBJECTIVE: The aim of this study was to determine the prevalence and demographics
      of benign vocal fold lesions (BVFL) and trends in its treatment in Korea based on
      data collected from the National Health Insurance Service database. MATERIAL AND
      METHODS: Data for patients diagnosed with BVFL (ICM-10 codes J381, J382, J384)
      from 2006 to 2015 were selected for analysis. Patient characteristics, including
      sex, age, income, area of residence, and comorbidity, were analyzed. Treatment
      was divided into surgical management and conservative management using operation
      codes. RESULTS: The prevalence and incidence of BVFL increased from 7.07% and
      5.29%, respectively, in 2006 to 12.47% and 7.98% in 2015. Compared with the non
      BVFL population, patients with BVFL were more likely to be female, reside in an
      urban area, and have gastroesophageal reflux disease. There was no significant
      change in the incidence of surgical treatment during the study period (around
      6000 per year); however, the surgical treatment rate decreased from 19.29% to
      8.38%. The probability of undergoing surgical treatment for BVFL was higher in
      men, those aged 50-59 years, and those in the lowest quartile for income, except
      for the medical aid group. CONCLUSION: In Korea, there was an increase in the
      number of patients diagnosed with BVFL and a decrease in the operation rate for
      this condition between 2006 and 2015. Diagnosis of BVFL varied significantly
      based on income and sex; however, the only variable affecting the operation rate
      was patient age.

PMID- 30193767
TI  - Harvesting responses to single pulse electrical stimulation for presurgical
      evaluation in epilepsy.

PMID- 30193768
TI  - Electrodiagnosis and nerve ultrasound: "Castor and Pollux" in the management of
      neuropathies.

PMID- 30193769
TI  - Inflammatory markers of CHMP2B-mediated frontotemporal dementia.
AB  - Histopathological studies and animal models have suggested an inflammatory
      component in the pathomechanism of the CHMP2B associated frontotemporal dementia
      (FTD-3). In this cross-sectional study, serum and cerebrospinal fluid were
      analyzed for inflammatory markers in CHMP2B mutation carriers. Serum levels of
      CCL4 were increased throughout life. Serum levels of IL-15, CXCL10, CCL22 and TNF
      alpha were significantly associated with cognitive decline, suggesting a
      peripheral inflammatory response to neurodegeneration. CSF levels of sTREM2
      appeared to increase more rapidly with age in CHMP2B mutation carriers. The
      identification of a peripheral inflammatory response to disease progression
      supports the involvement of an inflammatory component in FTD-3.

PMID- 30193770
TI  - Therapeutic effects of modified Devine surgery for concealed penis in children.
AB  - OBJECTIVE: Considerable controversy exists regarding the surgical indications for
      a concealed penis. We herein describe a modified technique for correction of a
      concealed penis. The superfluous inner plate is resected to accelerate the
      disappearance of the postoperative lymphedema, and the skin between the penis and
      scrotum is trimmed to recover the penoscrotal angle. METHODS: From January 2014
      to October 2017, 79 patients with a concealed penis underwent our modified Devine
      penoplasty procedure. We measured the penile length preoperatively and
      postoperatively to confirm the improvement. A questionnaire was administered to
      the patients' parents to assess satisfaction regarding penile size, morphology,
      voiding status, and hygiene. RESULTS: The perpendicular penile length was 1.88 +/
      0.76 cm preoperatively and 4.42 +/- 0.48 cm postoperatively, representing a
      significant improvement(p < 0.05). The parents' satisfaction grades for penile
      size, morphology, voiding status, and hygiene were significantly improved
      postoperatively (p < 0.05). Almost every patient had postoperative penile
      lymphedema; however, this symptom had spontaneously resolved by 6 weeks. No other
      complications occurred, such as skin necrosis, tissue contracture, or wound
      infection. CONCLUSION: The herein-described modified repair technique for a
      concealed penis was technically feasible and safe, and excellent postoperative
      satisfaction was achieved. Additionally, the postoperative penis exhibited a good
      cosmetic appearance. Because of the successful outcomes with few complications,
      we believe that this surgical method for selected patients with a concealed penis
      is more effective than the traditional method. LEVEL OF EVIDENCE: Level IV,
      therapeutic study.

PMID- 30193771
TI  - Sexual role and HIV-1 set point viral load among men who have sex with men.
AB  - BACKGROUND: HIV-1 set point viral load (SPVL) is a highly variable trait that
      influences disease progression and transmission risk. Men who are exclusively
      insertive (EI) during anal intercourse require more sexual contacts to become
      infected than exclusively receptive (ER) men. Thus, we hypothesize that EIs are
      more likely to acquire their viruses from highly infectious partners (i.e., with
      high SPVLs) and to have higher SPVLs than infected ERs. METHODS: We used a one
      generation Bernoulli model, a dynamic network model, and data from the
      Multicenter AIDS Cohort Study (MACS) to examine whether and under what
      circumstances MSM differ in SPVL by sexual role. RESULTS: Both models predicted
      higher SPVLs in EIs than role versatile (RV) or ER men, but only in scenarios
      where longer-term relationships predominated. ER and RV men displayed similar
      SPVLs. EI men remained far less likely than ER men to become infected, however.
      When the MACS data were limited by some estimates of lower sex partner counts (a
      proxy for longer relationships), EI men had higher SPVLs; these differences were
      clinically relevant (>0.3 log10 copies/mL) and statistically significant (p <
      0.05). CONCLUSIONS: Mode of acquisition may be an important aspect of SPVL
      evolution in MSM, with clinical implications.

PMID- 30193772
TI  - Integrated profiling of long non-coding RNAs and mRNAs identifies novel
      regulators associated with liver fibrosis.
AB  - Liver fibrosis is the underlying cause of cirrhosis and liver failure in any type
      of chronic liver injury. However, the function of lncRNAs in liver fibrosis is
      largely unknown. In this study, we performed transcriptome sequencing of CCl4
      induced mouse fibrotic liver tissues and normal liver tissues, and found 118
      lncRNAs and 1921 mRNAs were significantly up-regulated, whereas 59 lncRNAs and
      1504 mRNAs were down-regulated in fibrotic livers. Gene ontology analysis
      revealed that the differentially expressed lncRNAs are implicated in cell
      junction, cell differentiation and cell proliferation, pathways closely
      associated with EMT. The co-expression network of highly conserved lncRNAs and
      highly co-expressed mRNAs were constructed, whose differential expression were
      further confirmed by quantitative real-time PCR. Two highly conserved lncRNAs,
      Gm11149 and Gm20471, were identified to be significantly up-regulated in liver
      fibrosis. Their target genes, Ncam1 and Prrx1 respectively, are important
      modulators of EMT. Thus, the relative dynamic levels of Gm11149 and Ncam1,
      Gm20471 and Prrx1 were further monitored during the progress of liver fibrosis
      and their co-expression pattern was proved. Collectively, our results uncovered a
      crucial role of lncRNAs in the regulation of liver fibrosis and the lncRNA -mRNA
      network might provide new therapeutic strategies.

PMID- 30193773
TI  - Involvement of miR-455 in the protective effect of H2S against chemical hypoxia
      induced injury in BEAS-2B cells.
AB  - The protective effect of hydrogen sulfide (H2S) against hypoxia-induced injury
      via anti-apoptosis is well established, but the underlying mechanism remains
      unclear. The present study aimed to investigate whether miR-455 participated in
      the H2S protection of lung epithelial cells against CoCl2-induced apoptosis by
      regulating endoplasmic reticulum stress (ERS)-related genes. Human lung
      epithelial cells BEAS-2B were subjected to hypoxia injury with or without H2S
      preconditioning. It was found that hypoxia injury increased apoptosis of BEAS-2B
      cells, down-regulated the expression of miR-455, and upregulated the expression
      of calreticulin (Calr). H2S preconditioning attenuated lung epithelial cells
      apoptosis, enhanced cell viability, up-regulated the expression of miR-455, as
      well as down-regulated the expression of Calr following hypoxia injury. In
      addition, Calr, GRP78, C/EBP homologous protein (CHOP) and Caspase-12 protein was
      down-regulated by the miR-455 mimic and up-regulated by the miR-455 inhibitor.
      These results implicate miR-455 regulated H2S protection of lung epithelial cells
      against hypoxia-induced apoptosis by stimulating Calr.

PMID- 30193774
TI  - Assessment of SpondyloArthritis International Society (ASAS) Consensus on Spanish
      Nomenclature for Spondyloarthritis.
AB  - OBJECTIVE: To develop a consensus to standardize the use of Spanish terms,
      abbreviations and acronyms in the field of spondyloarthritis (SpA). METHODS: An
      international task force comprising all native Spanish-speaking Assessment of
      SpondyloArthritis International Society (ASAS) members, the executive committee
      of Grupo para el estudio de la Espondiloartritis de la Sociedad Espanola de
      Reumatologia (GRESSER), two methodologists, two linguists from the Real Academia
      Nacional de Medicina de Espana (RANM) and two patients from the Spanish
      Coordinator of Spondylitis Associations (CEADE) was established. A literature
      review was performed to identify the conflicting terms/abbreviations/acronyms in
      SpA. This review examined written sources in Spanish including manuscripts, ICF
      and ICD, guidelines, recommendations and consensuses. This was followed by a
      nominal group meeting and a three-round Delphi. The recommendations from the RANM
      based on the Panhispanic dictionary were followed throughout the process.
      RESULTS: Consensus was reached for 46 terms, abbreviations or acronyms related to
      the field of SpA. A Spanish translation was accepted for 6 terms and 6
      abbreviations to name or classify the disease, and for 6 terms and 4
      abbreviations related to SpA. It was agreed not to translate 15 acronyms into
      Spanish. However, when mentioning them, it was recommended to follow this
      structure: type of acronym in Spanish and acronym and expanded form in English.
      With regard to 7 terms or abbreviations attached to acronyms, it was agreed to
      translate only the expanded form and a translation was also selected for each of
      them. CONCLUSIONS: Through this standardization, it is expected to establish a
      common use of the Spanish nomenclature for SpA. The implementation of this
      consensus across the community will be of substantial benefit, avoiding
      misunderstandings and time-consuming processes.

PMID- 30193775
TI  - Use of semiquantitative analysis in local recurrence of colorectal carcinoma with
      18F-FDG PET/CT: A myth or a truth?
AB  - OBJECTIVE: Recurrence of colorectal cancer is mostly seen within the first 2
      years after surgery. The most frequent site of recurrence is the postsurgical
      areas and its surroundings. The purpose of this study was to evaluate the
      usefulness of semiquantitative analysis of 18Fluorine fluorodeoxyglucose (FDG)
      positron emission tomography/computed tomography (PET/CT) in determining
      recurrence of colorectal carcinoma in the operation site. MATERIAL AND METHODS:
      Files of 35 patients with colorectal carcinoma (25 men, 10 women, mean age:
      59.25+/-2.82 years, range: 27-80 years) who were treated with surgery and
      underwent FDG PET/CT scanning for restaging of colorectal carcinoma and showing
      increased FDG uptake in the postsurgical area, were retrospectively analysed.
      Besides calculating SUVmax of the areas showing FDG uptake, SUVmax of
      physiological colonic activity was also obtained and SUVmax of lesion/SUVmax of
      colonic wall (RSUVmax), was calculated. Characteristics of FDG uptake were
      classified according to histological analysis or clinical and imaging follow-up.
      RESULTS: In 17 of 35 patients (49%) the standard of reference for the final
      diagnosis was histologic analysis and in 18 (51%), final diagnosis was based on
      imaging and clinical follow-up. In 15 of 35 patients (43%) the etiology of
      increased FDG uptake was recurrence and in 20 (57%), FDG accumulation was
      observed due to benign etiology. The difference between the mean of the results
      of SUVmax in patients with recurrent disease and with no evidence of recurrence
      was statistically significant (P=.030). For SUVmax, a cut-off value for
      recurrence was calculated as 9.51 with a sensitivity of 80% and a specificity of
      70%. In terms of RSUVmax results, a statistically significant difference was also
      observed between mean values in patients with recurrent disease and in those
      without (P=.002). ROC analysis demonstrated that the best predictive value of
      RSUVmax for recurrence was 1.75 with a sensitivity of 67% and specificity of 95%.
      CONCLUSIONS: Semiquantitative analysis of FDG PET/CT may be used in detecting
      recurrent disease of patients with colorectal carcinoma. Eliminating interfering
      physiological colonic activity in analysis may have an incremental effect on the
      success of this technique, by means of increasing the specificity.

PMID- 30193776
TI  - Physiological and metabolic responses in newborn piglets associated with the
      birth order.
AB  - The objective of this study was to evaluate the effect of birth order on the
      physiological and metabolic responses of the newborn piglet the first hours after
      birth. A total of 281 randomly selected newborn piglets were included, classified
      according to birth order in 12 groups (L1-L12). The expulsion interval, neonatal
      vitality, latency in connecting to the maternal teat and physiological profile
      were recorded for each piglet. The number of piglets born alive and dead was also
      recorded. The blood gases, electrolytes and glucose levels of the neonates were
      obtained by means of an automatic blood gas and electrolyte analyzer. Groups L1,
      L2, L11, and L12 had the least score on the vitality scale, the longest expulsion
      intervals, and longest latency to connect with the maternal teat, as well as
      greater physiological alterations (hyperglycemia, hyperlactatemia and
      hypercapnia) compared to groups L4 to L9. Likewise, type-II stillbirths only
      occurred in the first and last quarter of the birth order of the litter. In
      conclusion, piglets born in the first and last quarter of the birth order of the
      litter had a greater risk of having physiological and behavioral alterations
      during farrowing.

PMID- 30193777
TI  - Transcriptomic analysis of the oviduct of pigs during the peri-conceptional
      period.
AB  - The optimal environment in the oviduct is created by adjusting its ultrastructure
      and secretory capacity to protect gametes and embryos. It was hypothesized that
      direct contact between the isthmic epithelium and 2- and 4-cell-stage embryos
      would alter the transcriptomic profile of the isthmus in pigs. Microarray
      analysis was performed to determine the alterations in gene expression of the
      isthmus on Days 2-3 of pregnancy in pigs (after natural mating) during embryo
      presence in the oviduct. Of 43,803 microarray probes, 354 (0.81%) transcripts
      were altered (P-value <= 0.05 and fold-change >= 1.2) on the days of pregnancy
      when assessments were made. Of these 354 transcripts, 118 (33.3%) were up
      regulated, and 236 (66.7%) were down-regulated. A total of 57 (48.3%) up
      regulated and 73 down-regulated (30.9%) transcripts were classified into gene
      ontology categories. Of the 354 altered genes, 36 (10.2%) were categorized into
      the Toll-like or NOD-like receptor signaling pathway, in the immune system
      subcategory. Selected genes engaged in maternal immune function were down
      regulated. The up-regulated genes were involved in epigenetic regulation, the
      protection of embryos against oxidative stress and xenobiotics and the control of
      estrogen metabolism. The 2- and 4-cell-stage embryos might, therefore, affect the
      oviductal transcriptome to optimize the intra-oviductal milieu, which is
      necessary to support proper development of embryos. The results of this study
      indicates the pig oviduct has the capacity to alter its transcriptomic profile as
      a result of early embryo development after natural mating.

PMID- 30193778
TI  - Influence of the symbiont Wolbachia on life history traits of the cabbage root
      fly (Delia radicum).
AB  - Wolbachia is an endocellular bacteria infecting arthropods and nematodes and is
      only transmitted vertically by females via the cytoplasm of the egg. It is often
      a manipulator of host reproduction, causing cytoplasmic incompatibility,
      thelytokous parthenogenesis, feminization or male killing, which all increase the
      proportion of infected females in the population. However, Wolbachia can modify
      life history traits of the host without causing the above phenotypes and each
      species illustrates the variability of relationships between this remarkably
      versatile symbiont and its many hosts. We have measured maternal transmission and
      the impact of a natural Wolbachia infection in the cabbage root fly Delia
      radicum, a major agricultural pest. We used a population that is polymorphic for
      the infection to ensure similar genetic and microbiome backgrounds between
      groups. Maternal transmission of the infection was 100% in our sample. We found
      no evidence of cytoplasmic incompatibility, thelytokous parthenogenesis,
      feminization nor male killing. Wolbachia infection significantly reduced hatch
      rate in infected eggs (by 10%) but improved larvo-nymphal viability sufficiently
      so that infected eggs nevertheless yielded as many adults as uninfected ones,
      albeit with a 1.5% longer total development time. Starved and infected
      ovipositing females suffered significantly reduced viability (20% higher
      mortality during a 3-day oviposition period) than uninfected females, but
      mortality was not higher in starved virgin females nor in starved males,
      suggesting that the energetic cost of the infection is only revealed in extreme
      conditions. Wolbachia had no effect on egg hatch time or offspring size. The
      apparently 100% vertical transmission and the significant but mutually
      compensating effects found suggest that infection might be nearly benign in this
      host and might only drift slowly, which would explain why the infection rate has
      been stable in our laboratory (approximately 50% individuals infected) for at
      least 30 generations.

PMID- 30193779
TI  - Longer life or more life: choose one please.

PMID- 30193780
TI  - When Should Guidelines Change? A Clarion Call for Evidence Regarding the Benefits
      and Risks of Screening for Colorectal Cancer at Earlier Ages.

PMID- 30193781
TI  - [Ulcerations of the extremities: An unusual manifestation of Behcet's disease].
AB  - BACKGROUND: Although cutaneous and mucosal involvement is a major manifestation
      in Behcet's disease, ulcerated lesions of the extremities are exceptional and
      poorly known. CASE REPORT: A 57-year-old male patient was diagnosed 7 years ago
      with Behcet's disease. This diagnosis was made in the presence of recurrent
      bipolar aphtous ulcers, pseudofolliculitis lesions and retinal vasculitis. After
      having been lost to follow up for two years, during which his treatment was
      discontinued, he presented centimetric necrotic ulcerations of the fingers of the
      hand and of the right big toe. The biopsy revealed leucocytoclastic and
      necrotizing vasculitis. The patient improved with antibiotic, oral
      corticosteroids, colchicine and local care. CONCLUSION: Linking extremity ulcers
      with Behcet's disease, though sometimes difficult, is essential for proper
      management.

PMID- 30193782
TI  - [Psychosomatic research in 2018: Lost illusions, renewed hopes].
AB  - A critical analysis of the basic hypotheses of psychosomatic research and the
      sometimes hasty assertions drawn from the previous works makes it possible to
      better discern the data confirmed by the most recent works or the most rigorous
      meta-analyses and to highlight the emerging tracks. If the hypothesis of
      behavioral patterns specifically related to the risk of certain pathologies seems
      abandoned, the predictive value of depression in the cardiovascular field, more
      than in that of oncology, becomes clearer. Negative affect and impaired emotional
      awareness emerge as two complementary factors of somatic vulnerability. Several
      vulnerability factors seem all the more effective as they affect individuals of
      lower socio-economic status. Social exclusion feeling and its links with the
      inflammatory response appear to be a possible common denominator, both for
      depression and for many somatic conditions. A series of studies on the cerebral
      regulation of emotions and stress, as well as on bidirectional brain-bowel
      relations and on the mediating role of the gut microbiota, complements the
      available epidemiological data. The same is true for certain advances in
      behavioral neuro-economics, which inform the decision-making processes of
      patients facing preventive health choices. Lastly, it appears that a significant
      part of the excess mortality associated with the existence of severe mental
      disorders is not due to factors inherent to the patients themselves, but to
      disparities in the quality of the care provided to them.

PMID- 30193783
TI  - Frailty in the End-Stage Lung Disease or Heart Failure Patient: Implications for
      the Perioperative Transplant Clinician.
AB  - The syndrome of frailty for patients undergoing heart or lung transplantation has
      been a recent focus for perioperative clinicians because of its association with
      postoperative complications and poor outcomes. Patients with end-stage cardiac or
      pulmonary failure may be under consideration for heart or lung transplantation
      along with bridging therapies such as ventricular assist device implantation or
      venovenous extracorporeal membrane oxygenation, respectively. Early
      identification of frail patients in an attempt to modify the risk of
      postoperative morbidity and mortality has become an important area of study over
      the last decade. Many quantification tools and risk prediction models for frailty
      have been developed but have not been evaluated extensively or standardized in
      the cardiothoracic transplant candidate population. Heightened awareness of
      frailty, coupled with a better understanding of distinct cellular mechanisms and
      biomarkers apart from end-stage organ disease, may play an important role in
      potentially reversing frailty related to organ failure. Furthermore, the clinical
      management of these critically ill patients may be enhanced by waitlist and
      postoperative physical rehabilitation and nutritional optimization.

PMID- 30193784
TI  - Ramelteon is Not Associated With Improved Outcomes Among Critically Ill Delirious
      Patients: A Single-Center Retrospective Cohort Study.
AB  - BACKGROUND: Delirium commonly affects critically ill patients and is associated
      with high morbidity and mortality. Some previous studies have suggested that
      ramelteon may prevent delirium, but ramelteon's impact on treating delirium is
      unknown. OBJECTIVE: To compare outcomes of critically ill delirious patients
      treated with ramelteon versus those who were not. METHODS: Retrospective cohort
      study of 322 intensive care unit patients stratified based on ramelteon exposure
      after a nonnegative Confusion Assessment Method-ICU score. MAIN OUTCOMES: Primary
      outcomes were hours alive without delirium or coma and likelihood of delirium
      coma resolution. Secondary outcomes were ventilator-free hours, likelihood of
      extubation, and mortality. RESULTS: Hazard ratios for delirium-coma resolution,
      extubation, and 10-day mortality were 1.05 (95% confidence interval 0.54-2.01),
      1.20 (95% confidence interval 0.47-3.03), and 0.31 (95% confidence interval 0.07
      1.32), respectively. Median delirium-coma free hours did not differ between
      ramelteon exposed and unexposed patients. Median ventilator-free hours were
      higher in the ramelteon group, however, ramelteon was administered postextubation
      in 92% of cases. CONCLUSIONS: Ramelteon was not associated with increased
      likelihood of delirium-coma resolution, extubation, or changes in mortality.

PMID- 30193786
TI  - Antimicrobial prophylaxis for transurethral resection of bladder tumor: A
      retrospective comparison of preoperative single-dose administration of
      piperacillin and tazobactam/piperacillin.
AB  - We aimed to clarify prophylactic antimicrobial effects of single-dose
      piperacillin (PIPC) for perioperative infections in the transurethral resection
      of bladder tumor (TURBT) in comparison with those of single-dose
      tazobactam/piperacillin (TAZ/PIPC) through a retrospective analysis. We analyzed
      data from 192 TURBT patients treated with single-dose (4 g) intravenous PIPC (P
      group) between April 2015 and April 2017. For comparison, we analyzed data from
      50 TURBT patients treated with single-dose (4.5 g) intravenous TAZ/PIPC (T/P
      group) between June 2013 and April 2014. We compared the perioperative incidences
      of fever (>=38  degrees C) and bacteriuria in the two groups. The number of
      febrile patients was four (2.1%) in the P group and one (2.0%) in the T/P group,
      without significant difference (p = 0.970). Among these febrile patients, urine
      and blood samples of two patients in the P group tested positive for bacterial
      cultures of Citrobacter koseri and Enterococcus faecalis, respectively. None of
      the patients in the T/P group tested positive for urine culture, postoperatively.
      However, 22 patients (18.2%) in the P group tested positive for urine culture,
      and Staphylococcus epidermidis (six patients), E. faecalis (three patients),
      Escherichia coli (three patients), Streptococcus agalactiae (two patients),
      Staphylococcus aureus (two patients), and C. koseri (one patient) were isolated.
      There was no significant difference in the incidence of bacteriuria in these two
      groups (p = 0.055). Based on these results, single-dose PIPC administration for
      the prevention of perioperative infections in TURBT was as effective as TAZ/PIPC.

PMID- 30193787
TI  - Filopodia and focal adhesions: An integrated system driving branching
      morphogenesis in neuronal pathfinding and angiogenesis.
AB  - Single cell branching during development in vertebrates is typified by neuronal
      branching to form neurites and vascular branches formed by sprouting
      angiogenesis. Neurons and endothelial tip cells possess subcellular protrusions
      that share many common features from the morphological to the molecular level.
      Both systems utilize filopodia as their cellular protrusion organelles and depend
      on specific integrin-mediated adhesions to the local extracellular matrix for
      guidance in their pathfinding. We discuss the similar molecular machineries
      involved in these two types of cell branch formation and use their analogy to
      propose a new mechanism for angiogenic filopodia function, namely as adhesion
      assembly sites. In support of this model we provide primary data of angiogenesis
      in zebrafish in vivo showing that the actin assembly factor VASP participates in
      both filopodia formation and adhesion assembly at the base of the filopodia,
      enabling forward progress of the tip cell. The use of filopodia and their
      associated adhesions provide a common mechanism for neuronal and endothelial
      pathfinding during development in response to extracellular matrix cues.

PMID- 30193785
TI  - Periodized low protein-high carbohydrate diet confers potent, but transient,
      metabolic improvements.
AB  - OBJECTIVE: Chronic ad libitum low protein-high carbohydrate diet (LPHC) increases
      health- and life-span in mice. A periodized (p) LPHC regimen would be a more
      practical long-term human lifestyle intervention, but the metabolic benefits of
      pLPHC are not known. Also, the interactions between LPHC diet and exercise
      training have not been investigated. Presently, we aimed to provide proof-of
      concept data in mice of the efficacy of pLPHC and to explore the potential
      interactions with concurrent exercise training. METHODS: A detailed phenotypic
      and molecular characterization of mice undergoing different durations of 14 d
      LPHC (5 E% protein)/14 d control diet cycles for up to 4 months with or without
      concurrent access to activity wheels allowing voluntary exercise training.
      RESULTS: pLPHC conferred metabolic benefits similar to chronic LPHC, including
      increased FGF21 and adaptive thermogenesis, obesity-protection despite increased
      total energy intake and improved insulin sensitivity. The improved insulin
      sensitivity showed large fluctuations between diet periods and was lost within 14
      days of switching back to control diet. Parallel exercise training improved
      weight maintenance but impaired the FGF21 response to pLPHC whereas repeated
      pLPHC cycles progressively augmented this response. Both the FGF21 suppression by
      exercise and potentiation by repeated cycles correlated tightly with Nupr1 mRNA
      in liver, suggesting dependence on liver integrated stress response. CONCLUSION:
      These results suggest that pLPHC may be a viable strategy to promote human health
      but also highlight the transient nature of the benefits and that the interaction
      with other lifestyle-interventions such as exercise training warrants
      consideration.

PMID- 30193788
TI  - Sesquiterpenoids from Vitex pierreana.
AB  - A new germacrane sesquiterpenoid with an epoxy moiety, pierreanin A (1), and a
      pair of unique cyclobutyl-containing sesquiterpenoid diastereoisomers,
      pierreanins B and C (2 and 3), were isolated from the branches and leaves of
      Vitex pierreana, together with 2 known analogues, identified as germacrone (4)
      and epiprocurcumenol (5). The structures of all isolates were evaluated by
      detailed analyses of NMR, IR, and MS data. The absolute configurations of 1-3
      were determined by comparison of the experimental ECD spectra with reported data
      of analogues containing the same chromophore. The ability of three new compounds
      to inhibit the growth of DU145 prostate cancer cells was also evaluated, as well
      as their inhibitory effects against the production of NO in LPS-stimulated
      RAW264.7 cells.

PMID- 30193789
TI  - Polyketide derivatives from the sponge associated fungus Aspergillus europaeus
      with antioxidant and NO inhibitory activities.
AB  - DPPH assay of the in-house marine-derived fungi uncovered that the EtOAc extract
      of the cultured fungus Aspergillus europaeus WZXY-SX-4-1, which was isolated from
      the marine sponge Xestospongia testudinaria, possesses radical scavenging
      activity. Chromatographic separation of the bioactive extract resulted in the
      isolation of 20 polyketide derivatives, including six new compounds namely
      eurobenzophenones A-C (1-3), euroxanthones A-B (4-5), and (+)1-O
      demethylvariecolorquinones A (6). The structures of new compounds were determined
      on the basis of the analyses of spectroscopic data, including the Snatzke method
      for the configurational assignment. Benzophenones 3, 9 and 10 exhibited potent
      radical scavenging activity against DPPH. All polyketides were evaluated for the
      inhibitory effects toward the LPS induced nitric oxide (NO) production in mouse
      microglia BV2 cells and the NF-kappaB activation in human colon carcinoma cell
      line SW480. Compound 9 with the significant DPPH radical scavenging activity is
      corresponded to the potent inhibition against NF-kappaB in SW480 cells induced by
      LPS. Compounds 2, 4, 16-18 exerted remarked down-regulation of NF-kappaB in LPS
      induced SW480 cells with weak inhibitory effects against NO production and the
      DPPH radical scavenging activity.

PMID- 30193790
TI  - The relationship between the neck circumference and the carotid intima-media
      thickness in Amerindians. Potential links to health risks?
AB  - The carotid intima media thickness (cIMT) is a predictor of cardiovascular
      events. The neck circumference (NC) has been investigated as a risk factor for
      increased cIMT with contradictory results. This study assessed the relationship
      between NC and cIMT in Atahualpa residents aged >=40 years who had sonographic
      examination of carotid arteries (n = 590). We also discussed on potential
      pathogenetic mechanisms underlying this association. Participants belonged to the
      Native Ecuadorian (Amerindians) ethnic group. Non-parametric regression models
      were used to assess the aforementioned relationship, after adjusting for relevant
      confounders. The mean age of participants was 60.9 +/- 12.7 years (58% women).
      The mean value of the cIMT was 0.85 +/- 0.19 mm. The mean NC was 35.8 +/- 34 cm.
      The NC was normally distributed, but the cIMT was not. Mean values of NC and cIMT
      were significantly greater in men than in women. Non-parametric models showed
      significant differences in median cIMT values according to quartiles of NC.
      Predictive cIMT margins increased by quartiles of NC, significantly among
      individuals in the 1st quartile as compared to the 3rd quartile. In this
      population of Amerindians, smaller NC is associated with lower values of cIMT.
      The pattern of this association is different in men than in women. Sex-related
      differences in cervical fat tissue distribution probably accounted for such
      differences.

PMID- 30193791
TI  - Re-thinking AF progression, or how to deal with electro-anatomical substrate in
      paroxysmal AF.

PMID- 30193792
TI  - Endothelial function is disturbed in a hypertensive diabetic animal model of
      HFpEF: Moderate continuous vs. high intensity interval training.
AB  - BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is associated
      with endothelial dysfunction, but the molecular mechanisms still remain unclear.
      Whether exercise training (ET) along with which optimal modality can improve
      endothelial function is controversial. The present study used a hypertensive,
      diabetic-driven HFpEF animal model (ZSF1 rats) to determine whether different
      training modalities (moderate-continuous (MCT) and high-intensity interval
      training (HIIT)) could reverse endothelial dysfunction and to understand the
      underlying molecular mechanisms. METHODS AND RESULTS: The development of HFpEF in
      ZSF1 obese animals was confirmed by echocardiography and hemodynamic
      measurements. Thereafter, animals were randomized into following groups: 1)
      sedentary, 2) 8 weeks of MCT, 3) 8 weeks of HIIT. ZSF1 lean animals served as
      control. In vitro measurement of endothelial function in aortic rings revealed
      significantly impaired endothelial-dependent and -independent vasodilation in
      HFpEF, which was reversed by MCT and HIIT. At the molecular level, the
      development of endothelial dysfunction was associated with a reduced expression /
      activation of endothelial nitric oxide synthase (eNOS), an increase in NADPH and
      activation of c-Jun N-terminal protein kinase (JNK), a reduced collagen I/III
      ratio and a reduced lining of the vessel wall by endothelial cells. ET primarily
      decreased NADPH oxidase expression, and JNK activation, elevated collagen I/III
      ratio while further improving aortic endothelial cell coverage. CONCLUSIONS: The
      present study provides evidence that endothelial dysfunction occurs in
      experimental HFpEF and that ET, independent of the studied training modality,
      reverses endothelial dysfunction and specific molecular alterations. ET may
      therefore provide an important therapeutic intervention for HFpEF patients.

PMID- 30193793
TI  - Improving health literacy in patients with chronic conditions: A call to action.
AB  - Knowledge and education is foundational to an individual receiving care, and
      health literacy is the ability of patients to understand and act on health
      information. Cardiovascular disease and diabetes are complex conditions that
      require active participation on the part of the patient. Lack of understanding on
      the condition and participation in self-care behaviors limits the effectiveness
      of treatment. An effective model is needed to better understand how patients with
      cardiovascular disease and diabetes acquire the knowledge and skills necessary to
      manage their health. In working together, the authors have created multiple
      programs that have been delivered at medical offices and corporations, resulting
      in a model for building functional and critical health literacy skills. This
      model is a progression that begins with health literacy, including the knowledge
      and understanding of the condition. Functional literacy includes numeracy, which
      is the ability to understand and manipulate numbers, and navigation, which is an
      understanding of what to do with the information. Finally, critical health
      literacy includes communication skills, including knowing what questions to ask
      and what information to share, and decision making, which can include shared
      decision making. These five levels of health literacy form a progression in the
      ability of the patient to become an active participant in their care, and inform
      the healthcare provider on effective educational methods.

PMID- 30193794
TI  - Vasopressin antagonism for decompensated right-sided heart failure.
AB  - BACKGROUND: Targeted treatment for decompensated right heart failure (RHF) with
      or without left heart failure is lacking. Vasopressin antagonists (vaptans) may
      offer an option by increasing urine output and fluid mobilization when used in
      acute decompensated RHF without impacting blood pressure or renal function, both
      common complications of loop diuretics. METHODS AND RESULTS: We searched
      electronic medical records from 2 institutions over 4 years for patients with RHF
      treated with vaptans. Urine output, creatinine, BUN and sodium, 1 day pre- versus
      1 day post-vaptan initiation were compared. Baseline (admission) pre-vaptan
      values for patients with RHF who met inclusion criteria (n = 112) were RAP,
      median (interquartile range) = 19 (13-24) mmHg; cardiac index, mean +/- standard
      deviation = 1.8 +/- 0.4 L/min/m2; BNP, 1078 (523-1690) pg/ml; creatinine
      clearance of 51 (39-69) ml/min, BUN, 37 (26-54) mg/dl, and serum [Na+] 132 (126
      135) mEq/L. Most patients (n = 103/112) received intravenous inotrope (prior to
      vaptan, n = 91). Overall length of stay was 27 (16-43) days. Vaptan treatment
      (90% tolvaptan, 10% conivaptan) was associated with increased 24 h urine output,
      1517 (906-2394) vs 2337 (1425-3744) mL, p = 0.005, and [Na+], 127 (124-130) vs
      130 (126-135) mEq/L, p = 0.001, without significant change in Cr or BUN.
      Furosemide IV dose equivalent decreased or remained unchanged in 75% of patients
      at 24 h and 64% at 72 h compared to the 24 h prior to vaptan use. CONCLUSION:
      Vaptans were associated with a significant increase in urine output and serum
      sodium with an apparent reduction or stabilization of furosemide equivalent
      dosing in the early treatment period in patients with decompensated RHF. Vaptans
      may offer a management option for patients failing conventional diuretic-based
      treatment.

PMID- 30193797
TI  - [Urethral prolapse: Diagnostic image of a rare pathology].

PMID- 30193795
TI  - Parkinson's disease does not alter automatic visual-motor coupling in postural
      control.
AB  - This study examined the coupling between visual information and body sway in
      patients with Parkinson's disease (PD) compared with healthy controls. Postural
      control performance was compared between 14 patients with PD (age: 69.6 +/- 8.8
      years - stages 1-3 of the Hoehn and Yahr scale) and 14 healthy control
      participants (age: 68.6 +/- 3.0 years). Participants stood upright in a moving
      room that remained motionless or continuously oscillated in the anterior
      posterior direction. Ten trials were performed in the following conditions: no
      movement of the room (1 trial) and with the room moving at frequencies of 0.1,
      0.17, and 0.5 Hz (3 trials each frequency). Body sway and moving room
      displacement were recorded. The results indicated that patients with PD displayed
      larger body sway magnitude in the stationary room condition. Body sway of
      patients with PD was induced by visual manipulation in all three visual stimulus
      frequencies, but body sway of patients with PD was less coherent compared to that
      of the control participants. However, no difference was observed in the visual
      body sway coupling structure. These results indicate that patients with PD can
      unconsciously couple body sway to visual information in order to control postural
      sway in a similar manner to healthy participants with intact visual-motor
      coupling for posture control. However, this coupling is marked by greater
      variability, indicating that people with PD have a motor system with greater
      inherent noise leading to a more varied behavior.

PMID- 30193796
TI  - Prefrontal cortex dysfunction during verbal fluency task after
      atypicalantipsychotic treatment in schizophrenia: A near-infrared spectroscopy
      imaging study.
AB  - A number of near-infrared spectroscopy (NIRS) studies in schizophrenia have shown
      that there is a significant dysfunction of the prefrontal cortex (PFC) in
      patients with schizophrenia, but it remains unclear how atypical antipsychotics
      affect the function of the PFC. To investigate the changes in brain activation
      patterns in schizophrenia who accepted antipsychotic treatment, we used NIRS to
      measure the hemodynamic changes of the PFC in patients with schizophrenia at the
      time of enrollment and after 4 weeks of treatment during a verbal fluency task
      (VFT). We included 16 schizophrenia and 17 sex- and age- matched healthy
      controls. Compared with the healthy controls, the VFT performance was
      significantly worse in patients with schizophrenia, as was the activation of the
      PFC. Furthermore, after 4 weeks of treatment, there was no significant
      improvement in VFT performance and the activation of the PFC in schizophrenia.
      Our results suggest that the function of the PFC and cognitive skills in
      schizophrenia were significantly impaired and do not improve from a short-term
      treatment of atypical antipsychotics.

PMID- 30193798
TI  - [Needs of schoolchildren with type 1 diabetes in Extremadura: Family
      perceptions].
AB  - INTRODUCTION: School-aged children with type 1 diabetes (DM1) require access to
      appropriate and safe care for their disease during their stay in the educational
      centre. OBJECTIVE: To identify the needs perceived by families of schoolchildren
      with DM1 that affect their educational integration, safety, and well-being during
      the school day. METHODOLOGY: A descriptive and cross-sectional study was
      conducted using a questionnaire based on information and opinions provided by
      families of 362 schoolchildren between 3 and 16 years old with DM1 registered in
      their health history in the Public Health System of Extremadura. RESULTS: The
      response rate was 56.9% (206). It was shown that 35% of schoolchildren with DM1
      were treated with continuous subcutaneous insulin infusion therapy. Almost all of
      them (95.1%) required glucose monitoring, and 57.8% required insulin
      administration during the school day. Most (88%) children had adjusted well to
      school and did not describe any type of discriminatory treatment (87.4%).
      Glucagon is available in 82% of educational centres, in which 43.7% had a trained
      adult person to administer it. That teachers could recognise a hypoglycaemia was
      expressed by 21.4% of the families, and 29.1% were unaware of the existence of
      coordination protocols in the school. More than half (58.7%) claimed that the
      information available in schools about diabetes was low, and 77.2% stated that
      the control of the disease would improve if more training was provided to
      teachers. CONCLUSIONS: There are aspects optimally covered in the care of
      schoolchildren with DM1 in the schools of Extremadura. Among situations
      identified with potential room for improvement were adherence to the coordination
      protocol, information about diabetes, and training of adults to deal with
      emergency situations.

PMID- 30193799
TI  - [Osteopetrosis, renal tubular acidosis, cerebral calcifications: a familial
      case].

PMID- 30193800
TI  - Implementing the comprehensive unit-based safety program model to improve the
      management of mechanically ventilated patients in Saudi Arabia.
AB  - BACKGROUND: Ventilator-associated events are common in mechanically ventilated
      patients. They are associated with more days on mechanical ventilation, longer
      intensive care unit (ICU) stay, and increased risk of mortality. Theoretically,
      interventions that prevent ventilator-associated events should also reduce
      associated morbidity. We evaluated the Comprehensive Unit-based Safety Program
      approach to improve the care of mechanically ventilated patients. METHODS: All
      mechanically ventilated patients admitted to the ICU between October 1, 2015, and
      October 31, 2016, were prospectively monitored for the development of ventilator
      associated events according to the National Healthcare Safety Network criteria. A
      process care bundle (endotracheal intubation with subglottic suctioning, head-of
      bed elevation >=30 degrees , target sedation scores, daily spontaneous awakening
      trials, spontaneous breathing trials), daily delirium assessment, and an early
      mobility protocol were instituted. The bundle compliance, ventilator-associated
      events rates, ICU length of stay, and mortality rate were noted. The database
      allowed viewing of current rates, trends, and averages of all participating
      sites. RESULTS: In the study period, 2,321 patients were admitted to the ICU, and
      1,231 required mechanical ventilation (10,342 ventilator days). There were 115
      ventilator-associated events: 82 ventilator-associated conditions, 15 infection
      related ventilator-associated conditions, and 18 possible cases of ventilator
      associated pneumonia. The ICU mortality rate was 13.3%, compared with 28.7% for
      those mechanically ventilated patients with ventilator-associated events (P =
      .0001). There was increased compliance for spontaneous awakening trials (51.5%
      76.9%, P = .0008) and spontaneous breathing trials (54.2%-72.2%, P = .02) and a
      decrease in infection-related ventilator-associated conditions (4.2-3.5 per 1,000
      days), possible cases of ventilator-associated pneumonia (2.1-1.7 per 1,000
      days), ICU mortality (45.3%-19.1%, P = .045), and ventilator-associated events
      associated mortality rates (33.3%-8.3%, P < .37). Physical therapy participation
      and mobility were 60.8% and 26.4%, respectively. CONCLUSION: The implementation
      of a multipronged program like the Comprehensive Unit-based Safety Program could
      improve the care processes and outcomes of mechanically ventilated patients.

PMID- 30193801
TI  - Effect of yoga on cortical inhibition in healthy individuals: A pilot study using
      Transcranial Magnetic Stimulation.

PMID- 30193802
TI  - Comparison of efficacy and toxicity between botulinum toxin subtypes A1 and A2 in
      cynomolgus macaques.
AB  - Botulinum toxin type A (subtype A1) is used as therapeutic agent for some
      neurological disorders causing spasticity. The toxin products have an upper
      dosage limit, and their adverse events, such as side effects of diffusion
      following high-dose administration, have become serious issues. Therefore, a
      preparation with greater therapeutic efficacy at lower dosages and less diffusion
      in the body is desired. We have attempted to produce neurotoxin derived from
      subtype A2 (A2NTX), which has a different amino acid sequence from that of
      neurotoxin derived from subtype A1. In this study, to investigate whether A2NTX
      is applicable for treatment, we compared the muscle relaxation effects and the
      toxicity between A1LL and A2NTX in adult cynomolgus macaques. In the isometric
      muscle contraction test elicited by 30 Hz tetanus stimulation, the contractions
      observed in the 0.4 U/site A1LL-treated group were similar in value to those in
      the 0.13 U/site A2NTX-treated group. In the toxicity test, the 12 and 24 U/kg
      A1LL- and A2NTX-treated groups all exhibited similar signs of toxicity regarding
      symptoms, rate of weight loss, and decrease in the length of the right lower leg
      perimeter. Thus, A2NTX demonstrated approximately 3.0-times higher muscle
      relaxation activity than A1LL, and their toxicity was equivalent. This study
      suggested that A2NTX products are more suitable for the treatment of neurological
      disorders.

PMID- 30193803
TI  - Brain-like emergent auditory learning: A developmental method.
AB  - Compared with machine audition, the human auditory system can recognize speech
      accurately and quickly. This paper proposes a new developmental network (DN) that
      simulates the human auditory system and constructs an artificial auditory model
      for speech recognition. The new model simulates each key element of the human
      auditory pathway as a deep network; in particular, an additional layer in the
      network is considered to simulate the function of the superior colliculus in the
      thalamus for speech context integration. The mel-frequency cepstral coefficient
      (MFCC) is used to extract the features of the speech signal as the sensory input
      of the DN. The emergent feature of DN model provides an explanation of how such
      internal neurons represent the short speech context when they are not supervised
      by the external world. The experimental results show that the recognition rates
      of English words and phrases can be improved significantly compared to those
      reported in the existing literature. The proposed DN model provides a new method
      to solve difficult problems, such as universal speech recognition, in traditional
      machine audition systems. Meanwhile, the same learning principle can potentially
      be used in or adapted to other computational contexts and applications.

PMID- 30193804
TI  - [Acceptability and effectiveness of immunotherapy in patients with melanoma].
AB  - The immunotherapies known as "inhibitors of checkpoint" (ICP) are monoclonal
      antibodies used since 2010 and have dramatically modified the management of the
      advanced or metastatic melanomas. By reactivating the anti-tumoral immune
      response, these antibodies can activate the immune system in all the tissues with
      a risk to induce immune related adverse events (IrAE). Thus, the adverse effect's
      profile of ICP is considered as very different from that usually associated with
      conventional chemotherapies. The objectives of our retrospective monocentric
      study were the evaluation of the real life's safety and efficiency of the
      ipilimumab and the pembrolizumab in patients with an advanced melanoma. Seventy
      two patients treated by ipilimumab and?or pembrolizumab between August 1st, 2008
      and December 31st, 2016 were investigated. The main IrAE occurring involved the
      gastro- intestinal, skin, and the endocrine systems. The average onset time of
      IrAE was 39, 104 and 68 days, respectively and their respective duration was of
      67, 50 and 111 days. There were 13 events of grade III and IV along with one
      death. The overall survival was 5 months for the patients treated in monotherapy
      with ipilimumab, and 14 months for those treated by pembrolizumab. Our real
      life's study tends to confirm the current safety profile of ICP treatment.
      Moreover and according to our analyses, the drug sequence seems to have a global
      survival impact.

PMID- 30193805
TI  - [From psychoactive medicines to addictovigilance in French Public Health Code
      (1990-2017)].
AB  - Addictovigilance in the French Public Health Code, in the section related to
      poisonous substances, refers to a monitoring system developed since 1990: control
      of psychoactive substances and products, with medicinal use or not, was completed
      by a specific system focused on evaluation and information on pharmacodependance
      in 1999. The French medicines agency (Agence du medicament) created in 1993 was
      involved in this monitoring system; pharmacodependance evaluation was added by
      law to the missions of the agencies that followed: the Agence francaise de
      securite sanitaire des produits de sante missions (AFSSAPS, 1998) and the Agence
      nationale de securite du medicament et des produits de sante (ANSM, 2011).
      "Addictovigilance" first appears in French Law in 2017 whereas it was used by
      pharmacodependance centers and AFSSAPS since 2007. Legal definition of
      addictovigilance in the French Public Health Code testified to public authorities
      action against addictive behavior whatever products status, legal or not. The
      visibility of addictovigilance is growing on the Internet as well (ANSM website,
      web portal for reporting adverse health events).

PMID- 30193806
TI  - Abnormal exercise echocardiography plus abnormal E/e' ratio at exercise portends
      worse outcome in patients with dyspnea.
AB  - BACKGROUND: The role of exercise echocardiography (ExE) for the assessment of
      patients with dyspnea is promising. We aimed to analyze the clinical
      characteristics and outcome of patients with this condition referred for ExE.
      METHODS: A total of 505 patients (66 +/- 11 years, 57% women) referred for
      evaluation of dyspnea were considered. Mitral regurgitation, ratio of early left
      ventricular inflow wave to early diastolic annulus wave (E/e'), and wall motion
      abnormalities (WMAs) were measured at rest and at exercise. Considered events
      were overall mortality, non-fatal myocardial infarction, late revascularization,
      and admission for heart failure. RESULTS: Ischemia was observed in 102 patients
      (20%), whereas WMAs were already present at rest in 55 patients (11%). A percent
      achieved of predicted metabolic equivalents >100% was found for most of the
      patients (70%). During a median follow-up of 3.50 years, 66 patients had events
      (annualized event rate 3.5%). An E/e' value of 13 at post-exercise was the best
      cut-off value to predict events. After adjustment by clinical and ExE variables,
      the combination of an abnormal ExE and E/e' values at post-exercise >=13 was an
      independent predictor of events (hazard ratio = 3.67, 95% confidence interval =
      2.11-6.38, p < 0.001). The worse outcome corresponded to patients with abnormal
      ExE and raised E/e' values at post-exercise (annualized event rate 17.2%).
      Patients with normal E/e' values at post-exercise had better outcome irrespective
      of the ExE results (annualized event rate 2.2% with normal ExE and 2.9% with
      abnormal ExE), whereas patients with high E/e' values at post-exercise but normal
      ExE results were at intermediate risk (annualized event rate 5.0%). CONCLUSIONS:
      Despite favorable ExE results, event rate remains high among patients with
      dyspnea referred for ExE, which may have a role to predict outcome in this
      setting. Patients with both raised E/e' values at post-exercise and abnormal ExE
      results are at the highest event risk.

PMID- 30193807
TI  - Modulation of human corneal stromal cell differentiation by hepatocyte growth
      factor and substratum compliance.
AB  - Corneal wound healing is a complex process that consists of cellular integration
      of multiple soluble biochemical cues and cellular responses to biophysical
      attributes associated with the matrix of the wound space. Upon corneal stromal
      wounding, the transformation of corneal fibroblasts to myofibroblasts is promoted
      by transforming growth factor-beta (TGFbeta). This process is critical for wound
      healing; however, excessive persistence of myofibroblasts in the wound space has
      been associated with corneal fibrosis resulting in severe vision loss. The
      objective of this study was to determine the effect of hepatocyte growth factor
      (HGF), which can modulate TGFbeta signaling, on corneal myofibroblast
      transformation by analyzing the expression of alpha-smooth muscle actin
      (alphaSMA) as a marker of myofibroblast phenotype particularly as it relates to
      biomechanical cues. Human corneal fibroblasts were cultured on tissue culture
      plastic (>1 GPa) or hydrogel substrates mimicking human normal or wounded corneal
      stiffness (25 and 75 kPa) in media containing TGFbeta1 +/- HGF. The expression of
      alphaSMA was analyzed by quantitative PCR, Western blot and immunocytochemistry.
      Cellular stiffness, which is correlated with cellular phenotype, was measured by
      atomic force microscopy (AFM). In primary human corneal fibroblasts, the mRNA
      expression of alphaSMA showed a clear dose response to TGFbeta1. The expression
      was significantly suppressed when cells were incubated with 20 ng/ml HGF in the
      presence of 2 ng/ml of TGFbeta1. The protein expression of alphaSMA induced by 5
      ng/ml TGFbeta1 was also decreased by 20 ng/ml of HGF. Cells cultured on hydrogels
      mimicking human normal (25 kPa) and fibrotic (75 kPa) cornea also showed an
      inhibitory effect of HGF on alphaSMA expression in the presence or absence of
      TGFbeta1. Cellular stiffness was decreased by HGF in the presence of TGFbeta1 as
      measured by AFM. In this study, we have demonstrated that HGF can suppress the
      myofibroblast phenotype promoted by TGFbeta1 in human corneal stromal cells.
      These data suggest that HGF holds the potential as a therapeutic agent to improve
      wound healing outcomes by minimizing corneal fibrosis.

PMID- 30193809
TI  - Effects of a 4-Week Self-Ankle Mobilization with Movement Intervention on Ankle
      Passive Range of Motion, Balance, Gait, and Activities of Daily Living in
      Patients with Chronic Stroke: A Randomized Controlled Study.
AB  - GOAL: To compare the effects of a 4-week self-ankle mobilization with movement
      training program with those of self-ankle mobilization with movement with a 10
      degrees  inclined board in patients with chronic stroke. MATERIALS AND METHODS: A
      randomized controlled assessor-blind trial was conducted. The patients were
      randomized into 2 arms. Subjects were 28 chronic stroke patients with hemiplegia.
      Both arms attended standard rehabilitation therapy for 30 minutes per session. In
      addition, self-ankle mobilization with movement and self-ankle mobilization with
      movement with a 10 degrees  inclined board trainings were performed 3 times per
      week for 4 weeks. Ankle dorsiflexion passive range of motion, static balance
      ability, Berg balance scale, gait parameters (walking speed, cadence, and step
      length), and activities of daily living were used to assess changes in motor
      function after training. FINDINGS: After 4 weeks of training, all dependent
      variables were significantly improved in both arms as compared with their
      baseline values. Furthermore, relative to the self-ankle mobilization with
      movement arm, the self-ankle mobilization with movement with a 10 degrees 
      inclined board arm demonstrated significantly improved ankle dorsiflexion passive
      range of motion, static balance ability, gait speed, cadence, and affected-side
      step length. CONCLUSIONS: Our results support the hypothesis that self-ankle
      mobilization with movement with a 10 degrees  inclined board combined with
      standard rehabilitation was superior to self-ankle mobilization with movement
      combined with standard rehabilitation with respect to the improvement in motor
      function in the patients with chronic stroke.

PMID- 30193808
TI  - Disrupting interaction of PSD-95 with nNOS attenuates hemorrhage-induced thalamic
      pain.
AB  - Hemorrhages occurring within the thalamus lead to a pain syndrome. Clinical
      treatment of thalamic pain is ineffective, at least in part, due to the elusive
      mechanisms that underlie the induction and maintenance of thalamic pain. The
      present study investigated the possible contribution of a protein-protein
      interaction between postsynaptic density protein 95 (PSD-95) and neuronal nitric
      oxide synthase (nNOS) to thalamic pain in mice. Thalamic hemorrhage was induced
      by microinjection of type IV collagenase into unilateral ventral posterior
      medial/lateral nuclei of the thalamus. Pain hypersensitivities, including
      mechanical allodynia, heat hyperalgesia, and cold allodynia, appeared at day 1
      post-microinjection, reached a peak 5-7 days post-microinjection, and persisted
      for at least 28 days post-microinjection on the contralateral side. Systemic pre
      treatment (but not post-treatment) of ZL006, a small molecule that disrupts PSD
      95-nNOS interaction, alleviated these pain hypersensitivities. This effect is
      dose-dependent. Mechanistically, ZL006 blocked the hemorrhage-induced increase of
      binding of PSD-95 with nNOS and membrane translocation of nNOS in thalamic
      neurons. Our findings suggest that the protein-protein interaction between PSD-95
      and nNOS in the thalamus plays a significant role in the induction of thalamic
      pain. This interaction may be a promising therapeutic target in the clinical
      management of hemorrhage-induced thalamic pain.

PMID- 30193810
TI  - Virtual Reality in Upper Extremity Rehabilitation of Stroke Patients: A
      Randomized Controlled Trial.
AB  - OBJECTIVE: Virtual reality game system is one of novel approaches, which can
      improve hemiplegic extremity functions of stroke patients. We aimed to evaluate
      the effect of the Microsoft Xbox 360 Kinect video game system on upper limb motor
      functions for subacute stroke patients. METHODS: The study included 42 stroke
      patients of which 35 (19 Virtual reality group, 16 control group) completed the
      study. All patients received 60 minutes of conventional therapy for upper
      extremity, 5 times per-week for 4 weeks. Virtual reality group additionally
      received Xbox Kinect game system 30 minutes per-day. Patients were evaluated
      prior to the rehabilitation and at the end of 4 weeks. Box&Block Test, Functional
      independence measure self-care score, Brunnstorm stage and Fugl-Meyer upper
      extremity motor function scale were used as outcome measures. RESULTS: The
      Brunnstrom stages and the scores on the Fugl-Meyer upper extremity, Box&Block
      Test and Functional independence measure improved significantly from baseline to
      post-treatment in both the experimental and the control groups. The Brunnstrom
      stage-upper extremity and Box&Block Test gain for the experimental group were
      significantly higher compared to the control group, while the Brunnstrom stage
      hand, the Functional independence measure gain and Fugl-Meyer gain were similar
      between the groups. CONCLUSIONS: We found evidence that kinect-based game system
      in addition to conventional therapy may have supplemental benefit for stroke
      patients. However, for virtual reality game systems to enter the routine practice
      of stroke rehabilitation, randomized controlled clinical trials with longer
      follow-up periods and larger sample sizes are needed especially to determine an
      optimal duration and intensity of the treatment.

PMID- 30193811
TI  - Evaluation of a CTA-Triage Based Transient Ischemic Attack Service: A
      Retrospective Single Center Cohort Study.
AB  - OBJECTIVE: We designed a computed tomography angiography (CTA)-based algorithm
      for patients presenting to hospital with a transient ischemic attack (TIA) which
      identified high-risk patients, as well as inpatient versus semiurgent outpatient
      management following MRI, and we hypothesised that this would be effective.
      METHODS: Patients seen in the ED at the Royal Adelaide Hospital from March 3,
      2012 to November 30, 2016 with TIA-like symptoms were assessed for a
      cardioembolic source (clinical assessment, electrocardiogram) and underwent intra
      and extracranial CTA. Patients with a referable >50% stenosis were admitted and
      given dual antiplatelets. Most high-risk cardiac source patients were also
      admitted and anticoagulated. Other patients were loaded with aspirin, or changed
      to clopidogrel if on aspirin, and reviewed as outpatients following semiurgent
      MRI (3-4 days). We assessed the 90-day recurrent stroke risk in this cohort as a
      whole, and in those with a final cerebrovascular diagnosis. RESULTS: 1167
      patients were diagnosed in Emergency as TIA and referred via our algorithm. A
      total of 150 were admitted, 78 had "high-risk" features. A total of 1017 patients
      were reviewed in the TIA clinic. The average age of the total cohort was 65.8
      years old. Final diagnosis was TIA/minor stroke in 69% admitted patients and 30%
      clinic patients (P value < .0001). The 90-day recurrent stroke risk in these
      patients was 2.0% (5.8% admitted vs .7% clinic patients, P value < .0001). In
      those with noncerebrovascular diagnoses, there were no recurrent strokes within
      90 days. CONCLUSIONS: Stroke risk is very low using CTA guided semiurgent clinic
      review algorithm.

PMID- 30193812
TI  - HLA-B*58:01 and rs9263726 have a linkage, but not absolute linkage disequilibrium
      in Han Chinese population.
AB  - HLA-B*58:01 has been demonstrated to be associated with allopurinol-induced
      severe cutaneous adverse reactions. Since HLA-B*58:01 is too complicated to be
      identified, it is necessary to select an appropriate surrogate biomarker. In
      Japan, the rs9263726 allele was considered as a surrogate biomarker for HLA
      B*58:01, but this was not the case with the Australian cohort. Due to the
      conflict results, in this study, we aim to demonstrate whether the rs9263726
      allele is a surrogate biomarker for HLA-B*58:01 in Han Chinese population. A
      total of 353 samples (200 cases from the south and 153 cases from the north) were
      selected to detect HLA-B*58:01 and rs9263726 allele. The HLA-B*58:01 was
      identified by sequencing-based method, and the rs9263726 allele was identified by
      Taqman SNP Genotyping Assays. The results showed that the two alleles had a
      linkage, but not absolute linkage disequilibrium in Han Chinese population.

PMID- 30193813
TI  - The quest for a nanoparticle-based vaccine inducing broad protection to influenza
      viruses.
AB  - Influenza virus infections are a significant public threat and the best approach
      to prevent them is through vaccination. Because of the perpetual changes of
      circulating influenza strains, the efficacy of influenza vaccines rarely exceeds
      50%. To improve the protection efficacy, we have designed a novel vaccine
      formulation that shows a broad range of protection. The formulation is made of
      the matrix protein 2 (M2e) and the nucleoprotein (NP) antigens. The
      multimerization of NP into nanoparticles improved significantly the immune
      response to NP. The combination of the NP nanoparticles with the PapMV-M2e
      nanoparticles enhances significantly the immune response directed to NP revealing
      the adjuvant property of the PapMV platform. The vaccine formulation combining
      these two types of nanoparticles protects mice from infectious challenges by two
      different influenza strains (H1N1 and H3N2) and is a promising influenza A
      vaccine capable to elicit a broad protection.

PMID- 30193815
TI  - Enhanced chemo-immunotherapy against melanoma by inhibition of cholesterol
      esterification in CD8+ T cells.
AB  - Cholesterol facilitated the formation of T cell receptor on cytotoxic CD8+ T
      lymphocytes (CTLs). However, the activation of CD8+ T cells always resulted in
      the upregulation of acetyl-CoA acetyltransferase-1 (ACAT-1) and enhanced the
      esterification of cholesterol. To relieve the suppression on CD8+ T cells, an
      ACAT-1 inhibitor avasimibe was combined with chemo-immunotherapy. Paclitaxel and
      immunoadjuvant alphaGC were co-encapsulated in liposomes modified with pH
      sensitive TH peptide (PTX/alphaGC-TH-Lip). After intravenous injections, the
      combination of avasimibe significantly elevated the free cholesterol level and
      relieved the inhibition of CD8+ T cells caused by PTX/alphaGC-TH-Lip, leading to
      enhanced CTL responses and anti-tumor effects of PTX/alphaGC-TH-Lip in B16F10
      melanoma xenograft and lung metastasis models. The adoptive immunotherapy further
      confirmed the enhanced anti-tumor immune responses of the combined strategy. The
      combination of avasimibe and PTX/alphaGC-TH-Lip was proven as a feasible approach
      to enhance the antitumor effects of chemo-immunotherapy by relieving the
      inhibition of CD8+ T cells.

PMID- 30193814
TI  - GRGDS-functionalized chitosan nanoparticles as a potential intravenous hemostat
      for traumatic hemorrhage control in an animal model.
AB  - Hemostats, which are used for immediate intervention during internal hemorrhage
      in order to reduce resulting mortality and morbidity, are relatively rare. Here,
      we describe novel intravenous nanoparticles (CPG-NPs-2000) with chitosan
      succinate (CSS) as cores, polyethylene glycol (PEG-2000) as spacers and a glycine
      arginine-glycine-aspartic acid-serine (GRGDS) peptide as targeted, active
      hemostatic motifs. CPG-NPs-2000 displayed significant hemostatic efficacy,
      compared to the saline control, CSS nanoparticles, and tranexamic acid in liver
      trauma rat models. Further studies have demonstrated that CPG-NPs-2000 are
      effectively cleared from organs and blood, within 2 and 48 h, respectively. In
      addition, administration of CPG-NPs-2000 does not affect clotting function under
      normal physiological conditions, indicating their potential safety in vivo. CPG
      NPs-2000 exhibit excellent thermal stability, good solubility, and redistribution
      ability, in addition to being low cost. These characteristics indicate that CPG
      NPs-2000 may have strong potential as effective intravenous hemostats for
      treating severe internal bleeding.

PMID- 30193816
TI  - Combined delivery of angiopoietin-1 gene and simvastatin mediated by anti
      intercellular adhesion molecule-1 antibody-conjugated ternary nanoparticles for
      acute lung injury therapy.
AB  - Effective treatment for acute lung injury (ALI) is in high demand. Lung-targeted
      ternary nanoparticles containing anti-intercellular adhesion molecule-1 (ICAM-1)
      antibody-conjugated simvastatin-loaded nanostructured lipid carrier (ICAM/NLC),
      protamine (Pro), and angiopoietin-1 (Ang-1) gene (ICAM-NLC/Pro/Ang) were
      developed for ALI therapy. The ternary nanoparticles with different weight ratios
      of ICAM-NLC to Ang-1 gene were prepared via charge interaction. The anti-ICAM-1
      antibody-conjugated ternary nanoparticles exhibited higher cellular uptake and
      transfection efficiency (from 26.7% to 30.9%) in human vascular endothelial cell
      line EAhy926 than the non-targeted control. The largest size of ICAM-NLC/Pro/Ang
      (357.1 nm) was employed for further study, which significantly up-regulated in
      vitro and in vivo Ang-1 protein expression. In vivo i.v. administration of ICAM
      NLC/Pro/Ang (357.1 nm) significantly attenuated pulmonary TNF-alpha and IL-6
      levels, inflammatory cell infiltration, and led to positive histological
      improvements in lipopolysaccharide-induced ALI mice. Collectively, the ICAM
      NLC/Pro/Ang that co-delivered simvastatin and Ang-1 gene may represent a
      potential treatment modality for ALI.

PMID- 30193817
TI  - Detrimental effect of type 2 diabetes mellitus in a large case series of
      Parkinson's disease.
AB  - INTRODUCTION: To investigate the effect of diabetes mellitus (DM) on the
      clinicoradiological features in patients with Parkinson's disease (PD). METHODS:
      671 patients with de novo PD were classified into two groups according to the
      presence of DM (106 with DM and 565 without). We performed inter-group
      comparative analyses of the striatal dopamine transporter (DAT) availability in
      all patients and level of cognitive performances in 312 patients (58 with DM and
      254 without). Neuroimaging analyses of cortical thickness were performed in 42
      patients with DM and 42 matched patients without DM. We assessed the longitudinal
      changes in the levodopa-equivalent dose (LED) across time in 549 patients who
      were treated for at least two years (86 with DM and 463 without) using a linear
      mixed model. RESULTS: The PD patients with DM were older at the onset of
      parkinsonism and had more severely decreased baseline DAT availability in the
      caudate and ventral striatum than those without DM. The PD group with DM showed
      poorer performances in attention/working memory and frontal/executive function
      than the group without DM. Cortical thinning in the right inferomedial temporal
      lobe was observed in PD with DM group relative to PD without DM group. During
      follow-up, the PD patients with DM showed a more rapid longitudinal increase in
      LED than those without DM. CONCLUSION: Our results suggest that coexistent DM may
      have a detrimental effect on disease progression as well as baseline striatal
      dopamine loss, brain structural alterations, and cognitive performances in
      patients with PD.

PMID- 30193818
TI  - Hypertrophy of nigral neurons in Torsin1A deletion (DYT1) carriers manifesting
      dystonia.
AB  - OBJECTIVE: To individuate morphometric changes and prevalent types of
      intraneuronal inclusions in nigral neurons of DYT1 dystonia autopsy-brains.
      METHODS: Using precise methods of quantification, such as unbiased stereology, we
      measured cellular and subcellular volumes of neuromelanin-containing (pigmented)
      neurons in the substantia nigra (SN) of DYT1 carriers with and without
      manifestation of generalized dystonia (manif-DYT1 and non-manif-DYT1,
      respectively), non-DYT1 carriers manifesting generalized dystonia (manif-non
      DYT1) patients, and age-matched control subjects (controls). A total of four DYT1
      carriers (two manif-DYT1 and two non-manif-DYT1), six manif-non-DYT1 carriers,
      and six controls autopsy-brains were available for these neuropathological
      morphometric analyses. The search of brain lesions was performed for: tau
      neurofibrillary tangles and neurites, extracellular beta-amyloid deposits, Lewy
      bodies and neurites, TorsinA, Laminin A + C, Ubiquitin, p62, pTDP43 intraneuronal
      inclusions; and Negri, Bunina, Hirano, Marinesco, Nissl, and Buscaino bodies.
      RESULTS: An increased mean cell body, nuclear, and nucleolar volume of nigral
      neurons in manif-DYT1 vs. non-manif-DYT1 (p < 0.0001), manif-non-DYT1 (p <
      0.0001), and controls (p < 0.00001) was found. Increased nuclear and nucleolar
      volumes in manif-non-DYT1 vs. controls were also found. None of the considered
      possible intraneuronal lesions were more frequent or prevalent in nigral neurons
      of manif-DYT1 vs. all the other groups. CONCLUSIONS: Unbiased stereology-based
      measurements of nigral neurons enlargement in manif-DYT1 in the absence of
      intraneuronal inclusions or neurodegenerative processes, is novel. These findings
      suggest distinct pathogenetic mechanisms between manif-DYT1 vs. non-manif-DYT1
      and manif-non-DYT1 dystonia, especially in terms of possible nigral dopaminergic
      abnormalities. These data could open new pathophysiologic views on specific
      dopamino-associated pathomechanisms related to the clinical manifestation of
      generalized dystonia.

PMID- 30193819
TI  - Two-dimensional Texture Analysis Based on CT Images to Differentiate Pancreatic
      Lymphoma and Pancreatic Adenocarcinoma: A Preliminary Study.
AB  - OBJECTIVE: To retrospectively assess the diagnostic performance of texture
      analysis and characteristics of CT images for the discrimination of pancreatic
      lymphoma (PL) from pancreatic adenocarcinoma (PA). METHODS: Fifteen patients with
      pathologically proved PL were compared with 30 age-matched controls with PA in a
      1:2 ratio. Patients underwent a CT scan with three phases including the
      precontrast phase, the arterial phase, and the portal vein phase. The regions of
      interest of PA and PL were drawn and analyzed to derive texture parameters with
      MaZda software. Texture features and CT characteristics were selected for the
      discrimination of PA and PL by the least absolute shrinkage and selection
      operator and logistic regression analysis. Receiver operating characteristic
      analysis was performed to assess the diagnostic performance of texture analysis
      and characteristics of CT images. RESULTS: Sixty texture features were obtained
      by MaZda. Of these, four texture features were selected by least absolute
      shrinkage and selection operator. Following this, three texture features and nine
      CT characteristics were excluded by logistic regression analysis. Finally, "S(5, 
      5)SumAverg" (texture feature) and "Size" (CT characteristic) were selected for
      the receiver operating characteristic analysis. The AUC of "S(5, -5)SumAverg" and
      "Size" were to be 0.704 and 0.821, respectively, with no significance between
      them (p = 0.3064). CONCLUSION: Two-dimensional texture analysis is a quantitative
      method for differential diagnosis of PL from PA. The diagnostic performance of
      both texture analysis and CT characteristics was similar.

PMID- 30193820
TI  - Small cells with big implications: Microglia and sex differences in brain
      development, plasticity and behavioral health.
AB  - Brain sex differences are programmed largely by sex hormone secretions and direct
      sex chromosome effects in early life, and are subsequently modulated by early
      life experiences. The brain's resident immune cells, called microglia, actively
      contribute to brain development. Recent research has shown that microglia are
      sexually dimorphic, especially during early life, and may participate in sex
      specific organization of the brain and behavior. Likewise, sex differences in
      immune cells and their signaling in the adult brain have been found, although in
      most cases their function remains unclear. Additionally, immune cells and their
      signaling have been implicated in many disorders in which brain development or
      plasticity is altered, including autism, schizophrenia, pain disorders, major
      depression, and postpartum depression. This review summarizes what is currently
      known about sex differences in neuroimmune function in development and during
      other major phases of brain plasticity, as well as the current state of knowledge
      regarding sex-specific neuroimmune function in psychiatric disorders.

PMID- 30193821
TI  - Call for an ezetimibe effectiveness test.

PMID- 30193822
TI  - Investigation on acceleration performance improvement of electro-hydraulic shake
      tables using parametric feedforward compensator and functional link adaptive
      controller.
AB  - Electro-hydraulic shake table (EHST), also known as earthquake simulator, is of
      considerable significance in civil engineering for evaluating structures or
      infrastructures subjected to earthquake ground motions. However, reproduction of
      prescribed accelerations at table for EHST systems remains to be imperfect as the
      whole systems are confronted with hydraulic nonlinearity, varying dynamics,
      unexpected disturbance, etc. For enhancing the acceleration tracking performance
      of EHST systems, an acceleration waveform reproduction strategy using offline
      designed parametric feedforward compensator (PFC) and online functional link
      adaptive controller (FLAC) is proposed in this paper. The PFC controller is
      established on the basis of classical three variable controller (TVC) as an inner
      compensation loop, in which multi-innovation forgetting gradient (MIFG) algorithm
      together with zero magnitude error tracking (ZMET) technique are utilized during
      the design process. The FLAC controller is combined to the PFC controller as an
      outer loop for further acceleration enhancement purpose, and the controller's
      nonlinear mapping ability is achieved with trigonometric expansion
      implementation. Following theoretical analysis of the proposed controller,
      comparative experiments are performed on an established unidirectional EHST test
      bench with both random and real-time recorded earthquake input waveforms. The
      experimental results validate the feasibility and superiority of the proposed
      acceleration reproduction strategy.

PMID- 30193824
TI  - Suboptimal diagnostic performance of dengue non-structural protein 1 antigen
      rapid test during non-endemic periods in southern Taiwan.

PMID- 30193825
TI  - The use of pulse oximetry to diagnose limb ischaemia.

PMID- 30193823
TI  - Lower expression of plasma-derived exosome miR-21 levels in HIV-1 elite
      controllers with decreasing CD4 T cell count.
AB  - Exosome-derived miR-21 was independently associated with CD4 T cell decline in
      HIV-1-infected elite controllers (OR 0.369, 95% CI 0.137-0.994, p = 0.049). Also,
      a negative correlation between miR-21 expression and MCP-1 level was found (r = 
      0.649, p = 0.020), while no correlation between soluble biomarkers or cellular
      immune activation was found.

PMID- 30193826
TI  - Techniques to enable identification and safe elevation of the posterior
      interosseous artery flap.

PMID- 30193827
TI  - Absorbable sutures for skin closure after carpal tunnel decompression: A Cochrane
      review summary.

PMID- 30193828
TI  - Orm/ORMDL proteins: Gate guardians and master regulators.
AB  - Sphingolipids comprise a diverse family of lipids that perform multiple functions
      in both structure of cellular membranes and intra- and inter-cellular signaling.
      The diversity of this family is generated by an array of enzymes that produce
      individual classes and molecular species of family members and enzymes which
      catabolize those lipids for recycling pathways. However, all of these lipids
      begin their lives with a single step, the condensation of an amino acid, almost
      always serine, and a fatty acyl-CoA, almost always the 16-carbon, saturated fatty
      acid, palmitate. The enzyme complex that accomplishes this condensation is serine
      palmitoyltransferase (SPT), a membrane-bound component of the endoplasmic
      reticulum. This places SPT in the unique position of regulating the production of
      the entire sphingolipid pool. Understanding how SPT activity is regulated is
      currently a central focus in the field of sphingolipid biology. In this review we
      examine the regulation of SPT activity by a set of small, membrane-bound proteins
      of the endoplasmic reticulum, the Orms (in yeast) and ORMDLs (in vertebrates). We
      discuss what is known about how these proteins act as homeostatic regulators by
      monitoring cellular levels of sphingolipid, but also how the Orms/ORMDLs regulate
      SPT in response to other stimuli. Finally, we discuss the intriguing connection
      between one of the mammalian ORMDL isoforms, ORMDL3, and the pervasive pulmonary
      disease, asthma, in humans.

PMID- 30193829
TI  - Porcine CD83 is a glycosylated dimeric protein existing naturally in membrane
      bound and soluble forms.
AB  - Human and mouse CD83 have been well characteized, however, the other mammalian
      CD83 genes have not been cloned and characterized. In this study, the porcine
      CD83 (pCD83) was cloned, expressed and characterized, and showed that the pCD83
      gene has 81% and 74% homologies with humans and mice, respectively, which was
      identified to be glycosylated when expressed in eukaryotic cells, existing
      naturally in two forms: membrance-bound CD83 (mCD83) and soluble CD83 (sCD83),
      the latter was identified to be generated mainly from mCD83 by proteolytic
      shedding. The pCD83 was a dimmer mediated by intermolecular disulfide bond formed
      by the fifth cysteine in the exrtracellular domain. Functionally, the recombinant
      porcine sCD83 was preliminarily tested to have the ability to inhibit DC-mediated
      T cell activition. This study provided necessary fundation for further
      investigation on pCD83 functions.

PMID- 30193830
TI  - Worldwide trends in insufficient physical activity from 2001 to 2016: a pooled
      analysis of 358 population-based surveys with 1.9 million participants.
AB  - BACKGROUND: Insufficient physical activity is a leading risk factor for non
      communicable diseases, and has a negative effect on mental health and quality of
      life. We describe levels of insufficient physical activity across countries, and
      estimate global and regional trends. METHODS: We pooled data from population
      based surveys reporting the prevalence of insufficient physical activity, which
      included physical activity at work, at home, for transport, and during leisure
      time (ie, not doing at least 150 min of moderate-intensity, or 75 min of vigorous
      intensity physical activity per week, or any equivalent combination of the two).
      We used regression models to adjust survey data to a standard definition and age
      groups. We estimated time trends using multilevel mixed-effects modelling.
      FINDINGS: We included data from 358 surveys across 168 countries, including 1.9
      million participants. Global age-standardised prevalence of insufficient physical
      activity was 27.5% (95% uncertainty interval 25.0-32.2) in 2016, with a
      difference between sexes of more than 8 percentage points (23.4%, 21.1-30.7, in
      men vs 31.7%, 28.6-39.0, in women). Between 2001, and 2016, levels of
      insufficient activity were stable (28.5%, 23.9-33.9, in 2001; change not
      significant). The highest levels in 2016, were in women in Latin America and the
      Caribbean (43.7%, 42.9-46.5), south Asia (43.0%, 29.6-74.9), and high-income
      Western countries (42.3%, 39.1-45.4), whereas the lowest levels were in men from
      Oceania (12.3%, 11.2-17.7), east and southeast Asia (17.6%, 15.7-23.9), and sub
      Saharan Africa (17.9%, 15.1-20.5). Prevalence in 2016 was more than twice as high
      in high-income countries (36.8%, 35.0-38.0) as in low-income countries (16.2%,
      14.2-17.9), and insufficient activity has increased in high-income countries over
      time (31.6%, 27.1-37.2, in 2001). INTERPRETATION: If current trends continue, the
      2025 global physical activity target (a 10% relative reduction in insufficient
      physical activity) will not be met. Policies to increase population levels of
      physical activity need to be prioritised and scaled up urgently. FUNDING: None.

PMID- 30193831
TI  - Surveillance of global physical activity: progress, evidence, and future
      directions.

PMID- 30193832
TI  - The need for paediatric registries to assess long-term brain effects of
      psychotropic medications: The case of bipolar disorder.

PMID- 30193833
TI  - Developmental dynamics of myogenesis in Pacific oyster Crassostrea gigas.
AB  - Pacific oyster (Crassostrea gigas) is a sessile bivalve living in the intertidal
      zone. It has become an attractive model for developmental studies due to its
      metamorphic transition from a mobile planktonic larvae to a sessile adults. To
      determine the effect of metamorphosis on muscle development in oyster larvae, we
      characterized myogenesis during larval development and metamorphosis by
      phalloidin staining which labels filamentous actin filaments. Our data revealed a
      dynamic pattern of myogenesis during embryonic and larval development. It appears
      that simple "U-shaped" muscle ring first developed at the trochophore stage. This
      was followed by a more complex musculature including an anterior adductor, velum
      ventral retractors at the veliger stage, and the addition of posterior adductors
      and foot retractors at the veliger and pediveliger stages. During metamorphosis,
      muscle structures in the anterior adductor, velum retractors and ventral
      retractors were degenerated. At the same time, mantle and gill musculature
      appeared and became the primary muscle system in juveniles together with the
      posterior adductor. In addition, indirect immunofluorescence with the monoclonal
      antibody against C. gigas muscle proteins (myosin heavy chains (MYHC) and alpha
      actinin) were used to monitor changes in the developing musculature at different
      larval stages. The immunofluorescence staining results of muscle proteins were
      consistent with phalloidin staining. The expression locations of two muscle
      proteins were similar and mainly located in larval velum retractor and adductor
      muscle. The alpha-actinin expression positions were located in Z-lined of velum
      striated retractors. Data from these studies provide a comprehensive description
      of myogenesis in C. gigas embryos and larvae. Moreover, our data showed that
      metamorphosis has a significant impact on remolding the musculature after
      transition from a mobile planktonic larvae to a sessile mollusk, associated with
      certain muscle group degradation.

PMID- 30193834
TI  - The prevalence and association of patients with impaired left ventricular
      ejection fraction and complete left bundle-branch block in Taiwan.
AB  - BACKGROUND/PURPOSE: A deleterious effect of complete left bundle-branch block
      (cLBBB) on left ventricular (LV) function has been established. The
      underutilization of cardiac resynchronization therapy has been noted in Taiwan
      and the Asian-Pacific area, but the reasons remain unclear. This study aimed to
      evaluate the prevalence and association of cLBBB and impaired LV ejection
      fraction (LVEF) in patients at the National Taiwan University Hospital (NTUH).
      METHODS: We enrolled 164,049 patients who underwent standard 12-lead
      electrocardiography (ECG) between January 2010 and December 2013 at NTUH.
      Echocardiographic examinations within one year of the index ECG were analyzed.
      Baseline clinical characteristics, electrocardiography and ECG parameters, in
      patients with cLBBB were compared among those with three different LVEFs (EF
      <35%, 35%<= EF<50%, and EF >=50%). Multivariable logistic regression analysis
      were conducted to identify independent predictors of impaired LVEF in patient
      with cLBBB. RESULTS: The prevalence of cLBBB was 0.4% (648 patients), and it
      increased with age. The estimated prevalence of cLBBB and LVEF <35% was about
      0.1%. The effects of age on the distributions of patients with cLBBB by three
      different EF statuses were significantly disparate. In patients with cLBBB aged
      >80 years, 64% had a normal EF. However, in those aged between 40 and 60 years,
      the risk of EF <35% was as high as 45%, and the risk of EF <50% was even higher
      at 60%. CONCLUSIONS: Patients in Taiwan had a low prevalence of LVEF<35% and
      cLBBB. About three-fourth of patients with cLBBB did not experience HF events,
      and 56% of them had a normal LVEF. The development of an effective triage
      strategy for these patients is warranted.

PMID- 30193835
TI  - Multiple subependymal pseudocysts in neonates play a role in later attention
      deficit hyperactivity and autistic spectrum disorder.
AB  - BACKGROUND/PURPOSE: To assess the long-term neurodevelopmental outcome of normal
      term neonates who were accidentally found to exhibit subependymal pseudocysts
      (SEPCs), frontal horn cysts, or choroid plexus cysts through cranial ultrasound
      (CUS) examination in a neonatal health examination. METHODS: In total, 5569
      neonates received CUS examination as an item in a health examination during the
      first week of birth between 2002 and 2012. Among them, 5147 infants fulfilled the
      inclusion criteria. The participants were aged between 5 and 15 years at the time
      when the data were collected. We retrospectively collected these data and
      interpreted their statistical significance by using one-way analysis of variance,
      Chi-square test with Yate's correction and odds ratios. RESULTS: The presence of
      SEPCs was significantly correlated with developmental delay and developmental
      disability, particularly with attention deficit hyperactivity disorder (ADHD) and
      autistic spectrum disorder (ASD). The risk of ADHD or ASD was significantly
      higher in participants with multiple SEPCs, among whom the odds ratios for ADHD
      and ASD were 6.50 (95% confidence interval [CI] = 2.27-18.64) and 28.54 (95% CI =
      5.98-136.36), respectively, higher than those for the total study population.
      CONCLUSIONS: Our data revealed multiple SEPCs in normal-term neonates as a risk
      factor for neurobehavioral outcome, particularly in ADHD and ASD. Simultaneously,
      the utility of CUS examination as a health examination item for neonates was
      confirmed.

PMID- 30193836
TI  - The association between clinical diagnostic factors and the prevalence of
      vertical root fracture in endodontic surgery.
AB  - BACKGROUND/PURPOSE: Diagnosis of vertical root fractures (VRFs) can often be
      challenging due to the similarity of signs and symptoms with other common dental
      infectious diseases. This study was aimed at evaluating the potential
      relationship between VRFs and commonly used clinical diagnostic factors. METHODS:
      330 root-filled teeth with endodontic failures were subjected to endodontic
      microsurgery over a six-year period. VRFs were identified in 61 teeth. A randomly
      age- and sex-matched retrospective case-control study was conducted on a subset
      of 59 root-filled teeth with VRFs (cases) and 177 root-filled teeth without VRFs
      (controls). The strength of association between preoperative signs and
      radiographic findings and VRFs was evaluated using logistic regression model.
      RESULTS: Sinus tract, periodontal pocket depth >=5 mm, periodontal swelling or
      abscess, and radiological image of J-shaped or "halo" radiolucency were
      significantly more frequent in cases than in controls (p < 0.05). With regard to
      logistic regression analysis, J-shaped or "halo" radiolucency demonstrated the
      greatest association with VRF, followed by periodontal pocket depth >=5 mm, sinus
      tract, and periodontal swelling or abscess. Approximately 70% of cases manifested
      themselves as combinations of at least two of these factors. Teeth having two and
      three or four of these factors had 3.14 times and 11.64 times higher risks for
      the presentations of VRFs, respectively (p < 0.001). CONCLUSION: The major risk
      for VRFs was represented by those presenting radiological image of J-shaped or
      "halo" radiolucency, periodontal pocket depth >=5 mm, sinus tract, and
      periodontal swelling or abscess simultaneously.

PMID- 30193837
TI  - Matrix mineralization controls gene expression in osteoblastic cells.
AB  - Osteoblasts are adherent cells, and under physiological conditions they attach to
      both mineralized and non-mineralized osseous surfaces. However, how exactly
      osteoblasts respond to these different osseous surfaces is largely unknown. Our
      hypothesis was that the state of matrix mineralization provides a functional
      signal to osteoblasts. To assess the osteoblast response to mineralized compared
      to demineralized osseous surfaces, we developed and validated a novel tissue
      surface model. We demonstrated that with the exception of the absence of mineral,
      the mineralized and demineralized surfaces were similar in molecular composition
      as determined, for example, by collagen content and maturity. Subsequently, we
      used the human osteoblastic cell line MG63 in combination with genome-wide gene
      set enrichment analysis (GSEA) to record and compare the gene expression
      signatures on mineralized and demineralized surfaces. Assessment of the 5 most
      significant gene sets showed on mineralized surfaces an enrichment exclusively of
      genes sets linked to protein synthesis, while on the demineralized surfaces 3 of
      the 5 enriched gene sets were associated with the matrix. Focusing on these three
      gene sets, we observed not only the expected structural components of the bone
      matrix, but also gene products, such as HMCN1 or NID2, that are likely to act as
      temporal migration guides. Together, these findings suggest that in osteoblasts
      mineralized and demineralized osseous surfaces favor intracellular protein
      production and matrix formation, respectively. Further, they demonstrate that the
      mineralization state of bone independently controls gene expression in
      osteoblastic cells.

PMID- 30193838
TI  - Kruppel-Like Factor 4 represses osteoblast differentiation via ciliary Hedgehog
      signaling.
AB  - Primary cilia are appendages observed in most types of cells, and serve as
      cellular antennae for sensing environmental signals. Evidence is accumulating
      that correct ciliogenesis and ciliary functions are indispensable for normal
      skeletal development by regulating signaling pathways important for bone
      development. However, whether ciliogenesis is regulated by bone-related factors
      in osteoblasts is largely unknown. Here we show that Kruppel-Like Factor 4
      (KLF4), which is known to repress osteoblast differentiation, supports the
      formation and maintenance of cilia in cultured osteoblasts; however, the length
      of the cilia observed in KLF4-induced cells were significantly shorter compared
      to the control cells. Basal Hedgehog signaling was repressed by KLF4.
      Significantly, activating Hedgehog signaling using a Smoothened agonist
      significantly rescued osteoblast mineralization and osteoblastic gene
      expressions. Global gene expression analysis showed that KLF4 induced number of
      genes including the nuclear receptor, Pregnane X receptor (PXR), and PXR
      repressed calvarial osteoblast mineralization and repressed Gli1 expression
      similar as the effect observed by inducing KLF4. Our results implicate that KLF4
      plays important roles for maintaining osteoblasts in an immature state by
      repressing basal activation of the Hedgehog signaling.

PMID- 30193839
TI  - A novel LPS-responsive beige-like anchor protein (LRBA) mutation presents with
      normal cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and overactive TH17
      immunity.

PMID- 30193840
TI  - The genetic landscape of severe combined immunodeficiency in the United States
      and Canada in the current era (2010-2018).

PMID- 30193841
TI  - B lymphocyte-induced maturation protein 1 (Blimp-1), a negative regulator of TH9
      development, orchestrates the resolution of airway inflammation in patients with
      allergic asthma.

PMID- 30193842
TI  - Functional characterization of four sex pheromone receptors in the newly
      discovered maize pest Athetis lepigone.
AB  - Chemoreception systems play a crucial role in regulating key behavioral
      activities of insects, such as mating, oviposition, and foraging. Odorant
      receptors (ORs) trigger the transduction of chemical signals into electric
      signals, and are involved in the corresponding responses associated with odorant
      guidance behaviors. Pheromone receptors (PRs) of male adult insects are generally
      thought to function in the recognition of female sex pheromones, and are also
      important molecular targets for the development of behavioral inhibitors and
      insecticides. In this study, we successfully expressed and functionally analyzed
      four AlepPRs of Athetis lepigone in Xenopus oocytes using the two-electrode
      voltage-clamp method. The results demonstrated that AlepOR3 responded exclusively
      to the sex pheromone compound of A. lepigone, (Z)-7-dodecenyl acetate (Z7-12:Ac)
      (EC50 = 8.830 * 10-6 M), while AlepOR4 responded to all five compounds [(Z7
      12:Ac, (Z)-8-dodecenyl acetate (Z8-12:Ac), (Z)-9-tetradecenyl acetate (Z9-14:Ac),
      (Z,E)-9,11-tetradecadienyl acetate (Z9,E11-14:Ac), and (Z,E)-9,12-tetradecadienyl
      acetate (Z9,E12-14:Ac)] and had a higher response to Z9-14:Ac (EC50 = 2.243 * 10
      5 M) than to Z7-12:Ac. However, AlepOR6 displayed a significantly higher response
      to a non-pheromone of A. lepigone, Z9,E12-14:Ac (EC50 = 7.145 * 10-6 M), than to
      the other four compounds. AlepOR5 displayed no responses to any of the pheromone
      compounds of A. lepigone, but responded exclusively to (Z)-11-hexadecenyl acetate
      (Z11-16:Ac) (EC50 = 7.870 * 10-6 M), a sex pheromone compound of other Noctuidae
      species. These findings can help explore the molecular mechanisms of sex
      pheromone recognition in A. lepigone and other moths, and develop broad-spectrum
      behavioral inhibitors and insecticides against different maize moths in future.

PMID- 30193843
TI  - Neuroendocrine and inflammatory responses to DHEA administration in young healthy
      women.
AB  - DHEA is reported to have beneficial effects for the elderly and for several
      pathologies because of its behavioral and anti-inflammatory properties. However,
      these properties have never been investigated in a young healthy population. The
      purpose of this double-blind, randomized study was therefore to investigate the
      effects of short-term DHEA administration (100 mg/day/4 weeks) on neuroendocrine
      (i.e., beta-endorphin and prolactin) and inflammatory (i.e., interleukin-6 and
      TNF-alpha) parameters in 10 young healthy female volunteers with regular sports
      practice. In parallel, the stress state was assessed with the Profile of Mood
      States (POMS) questionnaire. DHEA administration did not alter prolactin,
      interleukin-6 or TNF-alpha, and no significant change in tension, depression,
      anger, vigor, fatigue or confusion was noted. However, beta-endorphin levels
      increased significantly (p < 0.05) with the DHEA treatment. The results of this
      investigation indicate that short-term DHEA administration improves
      neuroendocrine modulation but does not affect the inflammatory status or
      psychological state in recreationally trained female athletes. Further studies
      are needed to determine the exact mechanisms and the responses of these
      parameters to DHEA administration at higher dosages and/or for longer durations,
      especially in response to physical/psychological stress.

PMID- 30193844
TI  - Outcomes and Quality of Life Among Men After Anal Sphincter-Sparing Transperineal
      Rectourethral Fistula Repair.
AB  - OBJECTIVE: To describe long-term quality of life (QOL) outcomes after
      rectourethral fistula (RUF) repair. RUF is a debilitating diagnosis and complex
      surgical dilemma with limited data regarding QOL after repair. METHODS: Patients
      at a tertiary referral center undergoing transperineal RUF repair 1/2009-5/2016
      were analyzed. Patients were contacted by telephone to assess QOL following
      repair. Descriptive analysis performed of short-term surgical data (success and
      complications) and long-term QOL data (novel questionnaire). RESULTS: Twenty one
      men underwent RUF surgery with 95% success after initial repair. Fifty two
      percent had a history of radiation and/or ablation. Four individuals (19%)
      experienced a Clavien-Dindo complication within 30 days, with 3 of those being
      grade III+. Fifteen had postoperative urinary incontinence, of whom 73% underwent
      artificial urinary sphincter placement. Three previously radiated individuals
      underwent subsequent urethral stricture surgery. At long-term follow-up (mean
      45.6 +/- 27.1 months), 53% reported perineal pain, 43% reported problems related
      to the gracilis flap, and 80% reported urinary incontinence (primarily occasional
      mild leakage). Twenty one percent were unable to do the things they wanted in
      their daily lives, while 80% reported that surgery positively impacted their
      life. None would have opted for complete urinary diversion. CONCLUSION: RUF
      repair leads to patient satisfaction and improved QOL, despite possible residual
      issues such as perineal pain and urinary incontinence. Definitive RUF repair
      should be offered to suitable radiated and nonradiated patients.

PMID- 30193845
TI  - Left frontal anodal tDCS increases approach motivation depending on reward
      attributes.
AB  - BACKGROUND: A growing body of literature indicates a correlation between
      asymmetrical activity of frontal brain sites and approach vs. withdrawal
      motivation. Yet the causal status of this relationship is presently unclear. Here
      we examined the effect of anodal tDCS applied over the left dorsolateral
      prefrontal cortex (dlPFC) on approach motivation, operationalized as effort
      allocation during the Effort-Expenditure for Reward Task (EEfRT). HYPOTHESIS: We
      expected left frontal anodal transcranial direct current simulation (tDCS) to
      increase participants' willingness to allocate more effort during the EEfRT.
      Based on previous research, we expected this effect to be strongest on trials
      with low probability of reward attainment. METHODS: 60 right-handed
      neurologically and psychologically healthy participants (63% female) aged 18-35
      were tested in a counterbalanced within-subject design. Participants were invited
      to our lab twice to complete two 15-min blocks of the EEfRT on each study day,
      randomly assigned to either an anodal tDCS or a SHAM condition. RESULTS: No main
      effect of stimulation condition was found, however the interactions of
      stimulation condition and both probability of reward attainment and reward
      magnitude reached significance. These interactions indicated that left frontal
      anodal tDCS specifically increased the percentage of hard task choices (HTC) in
      trials with low probability of reward attainment and in trials with high reward
      magnitude. DISCUSSION: The observation of an increasing effect of left frontal
      anodal tDCS on effort expenditure for reward as indicated by HTC supports the
      idea of a causal relationship between asymmetric activity of frontal brain sites
      and approach motivation and hints at moderating effects of task-features on the
      effects of tDCS.

PMID- 30193846
TI  - Asymmetric neural responses for facial expressions and anti-expressions.
AB  - Face recognition requires identifying both the invariant characteristics that
      distinguish one individual from another and the variations within the individual
      that correspond to emotional expressions. Both have been postulated to be
      represented via a norm-based code, in which identity or expression are
      represented as deviations from an average or neutral prototype. We used Fast
      Periodic Visual Stimulation (FPVS) with electroencephalography (EEG) to compare
      neural responses for neutral faces, expressions and anti-expressions. Anti
      expressions are created by projecting an expression (e.g. a happy face) through
      the neutral face to form the opposite facial shape (anti-happy). Thus expressions
      and anti-expressions differ from the norm by the same "configural" amount and
      thus have equivalent but opposite status with regard to their shape, but differ
      in their ecological validity. We examined whether neural responses to these
      complementary stimulus pairs were equivalent or asymmetric, and also tested for
      norm-based coding by comparing whether stronger responses are elicited by
      expressions and anti-expressions than neutral faces. Observers viewed 20 s
      sequences of 6 Hz alternations of neutral faces and expressions, neutral faces
      and anti-expressions, and expressions and anti-expressions. Responses were
      analyzed in the frequency domain. Significant responses at half the frequency of
      the presentation rate (3 Hz), indicating asymmetries in responses, were observed
      for all conditions. Inversion of the images reduced the size of this signal,
      indicating these asymmetries are not solely due to differences in the low-level
      properties of the images. While our results do not preclude a norm-based code for
      expressions, similar to identity, this representation (as measured by the FPVS
      EEG responses) may also include components sensitive to which configural
      distortions form meaningful expressions.

PMID- 30193847
TI  - CD56 Expression Marks Human Group 2 Innate Lymphoid Cell Divergence from a Shared
      NK Cell and Group 3 Innate Lymphoid Cell Developmental Pathway.
AB  - According to the established model of murine innate lymphoid cell (ILC)
      development, helper ILCs develop separately from natural killer (NK) cells.
      However, it is unclear how helper ILCs and NK cells develop in humans. Here we
      elucidated key steps of NK cell, ILC2, and ILC3 development within human tonsils
      using ex vivo molecular and functional profiling and lineage differentiation
      assays. We demonstrated that while tonsillar NK cells, ILC2s, and ILC3s
      originated from a common CD34-CD117+ ILC precursor pool, final steps of ILC2
      development deviated independently and became mutually exclusive from those of NK
      cells and ILC3s, whose developmental pathways overlapped. Moreover, we identified
      a CD34-CD117+ ILC precursor population that expressed CD56 and gave rise to NK
      cells and ILC3s but not to ILC2s. These data support a model of human ILC
      development distinct from the mouse, whereby human NK cells and ILC3s share a
      common developmental pathway separate from ILC2s.

PMID- 30193849
TI  - The Zinc-Finger Protein ZCCHC3 Binds RNA and Facilitates Viral RNA Sensing and
      Activation of the RIG-I-like Receptors.
AB  - Recognition of viral RNA by the retinoic acid-inducible gene-I (RIG-I)-like
      receptors (RLRs) initiates innate antiviral immune response. How the binding of
      viral RNA to and activation of the RLRs are regulated remains enigmatic. In this
      study, we identified ZCCHC3 as a positive regulator of the RLRs including RIG-I
      and MDA5. ZCCHC3 deficiency markedly inhibited RNA virus-triggered induction of
      downstream antiviral genes, and ZCCHC3-deficient mice were more susceptible to
      RNA virus infection. ZCCHC3 was associated with RIG-I and MDA5 and functions in
      two distinct processes for regulation of RIG-I and MDA5 activities. ZCCHC3 bound
      to dsRNA and enhanced the binding of RIG-I and MDA5 to dsRNA. ZCCHC3 also
      recruited the E3 ubiquitin ligase TRIM25 to the RIG-I and MDA5 complexes to
      facilitate its K63-linked polyubiquitination and activation. Thus, ZCCHC3 is a co
      receptor for RIG-I and MDA5, which is critical for RLR-mediated innate immune
      response to RNA virus.

PMID- 30193848
TI  - Antibodies Set Boundaries Limiting Microbial Metabolite Penetration and the
      Resultant Mammalian Host Response.
AB  - Although the mammalian microbiota is well contained within the intestine, it
      profoundly shapes development and metabolism of almost every host organ. We
      questioned the range and depth of microbial metabolite penetration into the host,
      and how this is modulated by intestinal immunity. Chemically identical microbial
      and host metabolites were distinguished by stable isotope tracing from 13C
      labeled live non-replicating Escherichia coli, differentiating 12C host isotopes
      with high-resolution mass spectrometry. Hundreds of endogenous microbial
      compounds penetrated 23 host tissues and fluids after intestinal exposure:
      subsequent 12C host metabolome signatures included lipidemia, reduced glycolysis,
      and inflammation. Penetrant bacterial metabolites from the small intestine were
      rapidly cleared into the urine, whereas induced antibodies curtailed microbial
      metabolite exposure by accelerating intestinal bacterial transit into the colon
      where metabolite transport mechanisms are limiting. Pervasive penetration of
      microbial molecules can cause extensive host tissue responses: these are limited
      by immune and non-immune intestinal mucosal adaptations to the microbiota.

PMID- 30193850
TI  - Can muscle weakness and disability influence the relationship between pain
      catastrophizing and pain worsening in patients with knee osteoarthritis? A cross
      sectional study.
AB  - OBJECTIVE: To verify if the relationship between pain catastrophizing and pain
      worsening would be mediated by muscle weakness and disability in patients with
      symptomatic knee osteoarthritis. METHODS: This was a cross-sectional study in a
      hospital out-patient setting. Convenience sampling was used with a total of 50
      participants with symptomatic knee osteoarthritis. Pain and the activities of
      daily livings (ADL) were assessed using the Knee Injury and Osteoarthritis
      Outcome Score (KOOS) subscale. Pain catastrophizing was assessed using the Coping
      Strategy Questionnaire (CSQ) subscale. Muscle strength of knee extension and 30-s
      chair stand test (30CST) were also assessed. Path analysis was performed to test
      the hypothetical model. Goodness of fit of models were assessed by using
      statistical parameters such as the chi-square value, goodness of fit index (GFI),
      adjusted goodness of fit index (AGFI), comparative fit index (CFI), and root mean
      square error of approximation (RMSEA). RESULTS: The chi-square values were not
      significant (chi-square=0.283, p=0.594), and the indices of goodness of fit were
      high, implying a valid model (GFI=1.000; AGFI=0.997; CFI=1.000; RMSEA=0.000).
      Pain was influenced significantly by muscle strength and ADL; muscle strength was
      influenced significantly by ADL via 30CST; ADL was influenced by pain
      catastrophizing. CONCLUSION: The relationship between pain catastrophizing with
      pain worsening are mediated by muscle weakness and disability.

PMID- 30193851
TI  - Clinical presentation and follow-up of women affected by Brugada syndrome.
AB  - BACKGROUND: Studies in Brugada syndrome (BrS) have mainly consisted of men.
      OBJECTIVE: The purpose of this study was to describe the clinical characteristics
      and arrhythmic risk factors in BrS women. METHODS: Consecutive BrS patients were
      enrolled from 1993 and followed prospectively. RESULTS: Among 1613 patients, 494
      were women (mean age 47 +/- 16 years). Women were more frequently asymptomatic
      than men (423 [86%] vs 867 [77%], respectively; P = .001) and less frequently had
      a spontaneous ECG pattern (107 [22%] vs 398 [36%], respectively; P <.001). During
      median [25th, 75th percentile] follow-up of 57 [23, 118] vs 62 [22, 113] months
      (P = .65), arrhythmic events occurred in 12 women (2%) vs 79 men (7%) (P =
      .0005). Mean age at the first event was 48.6 +/- 17.8 years for women vs 43 +/-
      14.2 years for men (P <.001). Gender was significantly related to cardiac events
      (hazard ratio [HR] 2.96; 95% confidence interval [CI] 1.6-5.4; P = .0005). In
      multivariate analysis, event predictors in women were index patient status (HR
      10.15; 95% CI 1.7-61.4; P = .01), previous sudden cardiac death (HR 69.4; 95% CI
      15-312.5; P <.0001), syncope (HR 6.8; 95% CI 1.4-34.5; P = .02), fragmented QRS
      (HR 20.2; 95% CI 1.8-228.9; P = .02), and QRS duration >120 ms (HR 4.7; 95% CI
      1.2-19.5; P = .03). CONCLUSION: Women represent a lower-risk group than men among
      individuals with BrS. In asymptomatic women, fragmented QRS and QRS >120 ms seem
      to be the only event predictors.

PMID- 30193852
TI  - Unexpected shift in circadian and septadian variation of sudden cardiac arrest:
      the Oregon Sudden Unexpected Death Study.
AB  - BACKGROUND: Earlier studies have reported both early morning and Monday peaks in
      occurrence of sudden cardiac arrest (SCA) in the community and appropriate
      defibrillator shocks in patients with an implantable cardioverter-defibrillator
      (ICD). However, a more recent analysis of ICD shocks reported absence of these
      peaks. OBJECTIVE: The purpose of this study was to perform a contemporary
      evaluation of the circadian and septadian variation of SCA in the general
      population. METHODS: The analysis was performed from an ongoing, population-based
      study of SCA in a Northwestern US community of approximately 1 million residents.
      To maximize accuracy, we focused on consecutive patients who presented with
      witnessed SCA and were attended by emergency medical services (EMS). The specific
      time of each SCA event was determined based on the time of the 911 call to EMS.
      RESULTS: During 2002-2014, we identified 1535 patients age >=18 years who
      suffered witnessed SCA, with time of first EMS contact recorded. There was no
      morning (6 AM to 12 PM) peak, and we observed a nadir in SCA events during 12 AM
      to 6 AM, with only 13.9% of events occurring during this 6-hour block (P <.0001).
      There was no peak on Mondays, but a nadir was observed on Sundays that accounted
      for only 11.3% of SCA events during the week (P = .004). CONCLUSION: in this
      contemporary community-based study, we failed to observe the expected morning
      peak or the Monday peak in SCA, duplicating recent findings in primary prevention
      defibrillator patients. The significant public health implications of these
      findings merit further investigation.

PMID- 30193853
TI  - Time interval from left ventricular stimulation to QRS onset is a novel predictor
      of nonresponse to cardiac resynchronization therapy.
AB  - BACKGROUND: Left ventricular (LV) lead placement at the late activation site
      (LAS) has been proposed as an optimal LV pacing site (ie, Q-LV interval).
      However, LAS may be relevant to local electrical conduction, measured as an
      interval from LV pacing stimulation to QRS onset (S-QRS interval). OBJECTIVE: The
      purpose of this study was to evaluate the prognostic value of S-QRS for reverse
      remodeling and the impact of S-QRS on pacing QRS configuration in patients
      undergoing cardiac resynchronization therapy (CRT). METHODS: Sixty consecutive
      heart failure patients with a wide QRS complex underwent CRT. A site with Q-LV
      >=95 ms was targeted for LV lead placement. A responder was defined as one with
      >15% reduction in LV end-systolic volume 6 months after CRT. RESULTS: LV lead
      placement with Q-LV >=95 ms was achieved in 52 of 60 patients (86.7%). Thirty-two
      of 52 patients (61.5%) were responders. S-QRS was significantly shorter in
      responders than nonresponders (P <.01), whereas Q-LV was not significantly
      different. A cutoff value of 37 ms for S-QRS had sensitivity and specificity of
      81% and 90%, respectively. Shorter S-QRS (<37 ms) showed significantly narrower
      LV pacing QRS width and biventricular pacing QRS width compared to longer S-QRS.
      After multivariate analysis, PQ interval (odds ratio 0.97; P = .01) and long S
      QRS >37 ms (odds ratio 0.014; P <.01) were independent predictors of response to
      CRT. CONCLUSION: In addition to a sufficient Q-LV, S-QRS can be a useful
      indicator of optimal LV lead position to achieve reverse remodeling. S-QRS
      contributes to the pacing QRS configuration associated with CRT response.

PMID- 30193854
TI  - Arrhythmogenic cardiac alternans in heart failure is suppressed by late sodium
      current blockade by ranolazine.
AB  - BACKGROUND: Cardiac alternans is promoted by heart failure (HF)-induced calcium
      (Ca2+) cycling abnormalities. Late sodium current (INa,L) is enhanced in HF and
      promotes Ca2+ overload; however, mechanisms underlying an antiarrhythmic effect
      of INa,L blockade in HF remain unclear. OBJECTIVE: The purpose of this study was
      to determine whether ranolazine suppresses cardiac alternans in HF by normalizing
      Ca2+ cycling. METHODS: Transmural dual optical mapping of Ca2+ transients and
      action potentials was performed in wedge preparations from 8 HF and 8 control
      (normal) dogs. Susceptibility to action potential duration alternans (APD-ALT)
      and Ca2+ transient alternans (Ca-ALT) was compared at baseline and with
      ranolazine (5-10 MUM). RESULTS: HF increased APD- and Ca-ALT compared to normal
      (both P <.05), and ranolazine suppressed APD- and Ca-ALT in both groups (P <.05).
      The incidence of spatially discordant alternans (DIS-ALT) was increased by HF
      (8/8) compared to normal (4/8; P <.05), and ranolazine decreased DIS-ALT in HF
      (4/8; P <.05).Not only did ranolazine mitigate HF-induced Ca2+ overload, it also
      attenuated APD-ALT to Ca-ALT gain (amount of APD-ALT produced by Ca-ALT). In HF,
      APD-ALT to Ca-ALT gain was significantly increased (0.55 +/- 0.02) compared to
      normal (0.44 +/- 0.02; P <.05) and was normalized by ranolazine (0.36 +/- 0.05; P
      <.05), representing a complementary mechanism by which INa,L blockade suppressed
      cardiac alternans. CONCLUSION: Ranolazine attenuated arrhythmogenic cardiac
      alternans in HF, both by suppressing Ca-ALT and decreasing the coupling gain of
      APD-ALT to Ca-ALT. Blockade of INa,L may reverse impaired Ca2+ cycling to
      mitigate cardiac alternans, representing a mechanism underlying the
      antiarrhythmic benefit of INa,L blockade in HF.

PMID- 30193855
TI  - Candidatus Prosiliicoccus vernus, a spring phytoplankton bloom associated member
      of the Flavobacteriaceae.
AB  - Microbial degradation of algal biomass following spring phytoplankton blooms has
      been characterised as a concerted effort among multiple clades of heterotrophic
      bacteria. Despite their significance to overall carbon turnover, many of these
      clades have resisted cultivation. One clade known from 16S rRNA gene sequencing
      surveys at Helgoland in the North Sea, was formerly identified as belonging to
      the genus Ulvibacter. This clade rapidly responds to algal blooms, transiently
      making up as much as 20% of the free-living bacterioplankton. Sequence similarity
      below 95% between the 16S rRNA genes of described Ulvibacter species and those
      from Helgoland suggest this is a novel genus. Analysis of 40 metagenome assembled
      genomes (MAGs) derived from samples collected during spring blooms at Helgoland
      support this conclusion. These MAGs represent three species, only one of which
      appears to bloom in response to phytoplankton. MAGs with estimated completeness
      greater than 90% could only be recovered for this abundant species. Additional,
      less complete, MAGs belonging to all three species were recovered from a mini
      metagenome of cells sorted via flow cytometry using the genus specific ULV995
      fluorescent rRNA probe. Metabolic reconstruction indicates this highly abundant
      species most likely degrades proteins and the polysaccharide laminarin.
      Fluorescence in situ hybridisation showed coccoid cells, with a mean diameter of
      0.78mm, with standard deviation of 0.12MUm. Based on the phylogenetic and genomic
      characteristics of this clade, we propose the novel candidate genus Candidatus
      Prosiliicoccus, and for the most abundant and well characterised of the three
      species the name Candidatus Prosiliicoccus vernus.

PMID- 30193856
TI  - SELEX methods on the road to protein targeting with nucleic acid aptamers.
AB  - Systematic evolution of ligand by exponential enrichment (SELEX) is an efficient
      method used to isolate high-affinity single stranded oligonucleotides from a
      large random sequence pool. These SELEX-derived oligonucleotides named aptamer,
      can be selected against a broad spectrum of target molecules including proteins,
      cells, microorganisms and chemical compounds. Like antibodies, aptamers have a
      great potential in interacting with and binding to their targets through
      structural recognition and are therefore called "chemical antibodies". However,
      aptamers offer advantages over antibodies including smaller size, better tissue
      penetration, higher thermal stability, lower immunogenicity, easier production,
      lower cost of synthesis and facilitated conjugation or modification with
      different functional moieties. Thus, aptamers represent an attractive
      substitution for protein antibodies in the fields of biomarker discovery,
      diagnosis, imaging and targeted therapy. Enormous interest in aptamer technology
      triggered the development of SELEX that has underwent numerous modifications
      since its introduction in 1990. This review will discuss the recent advances in
      SELEX methods and their advantages and limitations. Aptamer applications are also
      briefly outlined in this review.

PMID- 30193857
TI  - The King-Devick test is not sensitive to self-reported history of concussion but
      is affected by English language skill.
AB  - OBJECTIVES: Head injuries, including concussion, are a concern in many sports.
      Current validated concussion assessment protocols such are problematic with
      suggestions that an oculomotor examination, such as the King-Devick (K-D) test,
      could be included. This research explores the role of the K-D test in snowsport
      concussion research. DESIGN: Experienced snowsport participants were recruited
      through a western Canadian resort (n=75). METHODS: Participants completed a
      questionnaire that included their history of prior serious head impacts and were
      assessed via the computer-based K-D test in English. RESULTS: Of the 75
      participants, 23 (69%) reported at least one previous serious head impact.
      English was the not primary language for seven participants. Independent sample t
      tests revealed: significant differences in the K-D average saccade scores for
      those who had broken their helmets, with or without a serious head injury (x
      =171.23, SD=12.9) and those who had not broken a helmet (x-=186.61, SD=20.18; t
      (70)=-2.53, p=.014, twotailed) and significant differences in the K-D time for
      those whose native language is English (x-=47.9, SD=6.3) and those where English
      was not their first language (x-=53.3, SD=7.4; t(73)=.48, p=.04), but no
      significant difference for their saccade velocities: English (x-=183.64, SD=20.0)
      versus those where English is a second or third language (x-=188.44, SD=20.1;
      t(70)=-.56, p=.576). CONCLUSIONS: For subjects whose first language is not
      English, such as in many snowsport resorts, the K-D test may need to be conducted
      in a person's native language to provide a valid assessment based upon the time
      to complete the task.

PMID- 30193858
TI  - The promoting effect of enteric materials on the oral absorption of larotaxel
      loaded polymer-lipid hybrid nanoparticles.
AB  - Enteric polymers have been found with absorption promotion effect on
      nanoparticles. To study the role of enteric polymers played in the process of
      oral nanoparticle delivery, Eudragit L100-55 (EU) and sodium alginate (SA) were
      selected as model enteric polymers and larotaxel (LTX) as model drug. Suspensions
      composed of LTX-loaded nanoparticles, HPMC and different enteric polymers (EU and
      SA) were prepared (NP@EU, NP@SA). And aspects like precipitate morphology upon
      contact with acid, nanoparticle encapsulation capability, in vitro drug release,
      intestinal residence and in vivo oral bioavailability were studied. It was found
      that precipitates formed by EU could encapsulate more NP in acidic environment
      than those of SA (>95% of EU vs. approximately 70% of SA), and this difference in
      NP encapsulation was found correlated with the morphology of the precipitates
      formed: precipitates of EU appeared as three dimensional granules with dense
      inner structure, while SA precipitated into film-like porous structures. Results
      of pharmacokinetic study indicated that both EU and SA were capable in improving
      LTX absorption with absolute bioavailability of 77.1% and 42.5%, respectively.
      And the better absorption promoting effect of NP@EU was correlated with its
      longer intestinal residence shown by the results of ex vivo imaging study. In
      conclusion, both EU and SA could improve the oral bioavailability of LTX-loaded
      NP, and NP encapsulation capability and intestinal residence time are considered
      as key factors affecting the degree of absorption promotion.

PMID- 30193859
TI  - Novel chitosan-based solid-lipid nanoparticles to enhance the bio-residence of
      the miraculous phytochemical "Apocynin".
AB  - Apocynin (APO), a specific NADPH oxidase inhibitor, is a bioactive phytochemical
      that exhibits versatile pharmacological activities. However, its rapid
      elimination and poor bioavailability represent great challenges to pharmaceutical
      scientists. Accordingly, novel chitosan-based APO-loaded solid lipid
      nanoparticles (CS,APO - loaded SLNS) were developed to address such obstacles. A
      full 24 factorial design of experiment approach was employed to evaluate the
      individual and combined effect of critical process parameters namely; the amount
      of glycerol tristearate (GTS, XA) and sucrose mono palmitate (SMP, XB) as well as
      the concentration of chitosan (CS, XC) and polyvinyl alcohol (PVA, XD), on
      different critical quality attributes. Full characterization and extensive in
      vitro-in vivo evaluations of the optimized SLNs formula were conducted. The
      optimized formula, with core (CS,APO) and shell (PVA), has enhanced oral and
      intravenous bioavailability in rats as clearly verified when compared with APO
      solution. Probably, PVA hindered opsonization intravenously and SLNs reduced pre
      systemic effect. In conclusion, the novel chitosan-based SLNs system would open
      new vistas in potentiating the bioavailability and sustaining the effect of APO
      and other bioactive phytochemicals with comparable properties.

PMID- 30193860
TI  - SNHG12 Promotes Angiogenesis Following Ischemic Stroke via Regulating miR
      150/VEGF Pathway.
AB  - The promotion of angiogenesis is a promising therapeutic strategy for ischemic
      stroke. Many long noncoding RNAs (lncRNAs) are related to angiogenesis following
      ischemic stroke. LncRNA small nucleolar RNA host gene 12 (SNHG12) was upregulated
      in oxygen-glucose deprivation (OGD)-exposed primary brain microvascular
      endothelial cells and in microvessel from middle cerebral artery occlusion (MCAO)
      animal brains. However, the role and underlying mechanism of SNHG12 in ischemic
      stroke especially associated with angiogenesis process remain unknown. The
      expression of SNHG12 and miR-150 was determined in OGD-stimulated mouse brain
      microvascular endothelial (bEnd.3) cells. The role and mechanism of SNHG12 in the
      angiogenesis after ischemic stroke were investigated using gain- and loss-of
      function approaches both in OGD-exposed bEnd.3 cells and in MCAO mouse models. We
      found SNHG12 expression was elevated, whereas miR-150 reduced in OGD-exposed
      bEnd.3 cells. Upregulation of SNHG12 elevated, and SNHG12 knockdown suppressed
      the capillary-like tube formation, viability, migration, and VEGF expression in
      OGD-injured bEnd.3 cells. miR-150 mimic reversed, whereas anti-miR-150 further
      strengthened the effect of SNHG12 upregulation on the angiogenesis in bEnd.3
      cells. Furthermore, we found that SNHG12 functioned as a competing endogenous RNA
      for miR-150 to regulate VEGF expression. Additionally, overexpression of SNHG12
      improved the recovery of neurological function, reduced infarct volume and miR
      150 expression, increased vascular density and VEGF expression in the infarct
      border zone of MCAO mice. In conclusion, SNHG12 promotes the angiogenesis
      following ischemic stroke via miR-150/VEGF pathway, which further clarified the
      mechanism of angiogenesis after ischemic stroke and provides a target for the
      treatment of this disease.

PMID- 30193861
TI  - Brain Stem Neural Circuits of Horizontal and Vertical Saccade Systems and their
      Frame of Reference.
AB  - Sensory signals for eye movements (visual and vestibular) are initially coded in
      different frames of reference but finally translated into common coordinates, and
      share the same final common pathway, namely the same population of extraocular
      motoneurons. From clinical studies in humans and lesion studies in animals, it is
      generally accepted that voluntary saccadic eye movements are organized in
      horizontal and vertical Cartesian coordinates. However, this issue is not settled
      yet, because neural circuits for vertical saccades remain unidentified. We
      recently determined brainstem neural circuits from the superior colliculus to
      ocular motoneurons for horizontal and vertical saccades with combined
      electrophysiological and neuroanatomical techniques. Comparing well-known
      vestibuloocular pathways with our findings of commissural excitation and
      inhibition between both superior colliculi, we proposed that the saccade system
      uses the same frame of reference as the vestibuloocular system, common
      semicircular canal coordinate. This proposal is mainly based on marked
      similarities (1) between output neural circuitry from one superior colliculus to
      extraocular motoneurons and that from a respective canal to its innervating
      extraocular motoneurons, (2) of patterns of commissural reciprocal inhibitions
      between upward saccade system on one side and downward system on the other, and
      between anterior canal system on one side and posterior canal system on the
      other, and (3) between the neural circuits of saccade and quick phase of
      vestibular nystagmus sharing brainstem burst neurons. In support of the proposal,
      commissural excitation of the superior colliculi may help to maintain Listing's
      law in saccades in spite of using semicircular canal coordinate.

PMID- 30193862
TI  - Structural and functional characterization of a maltose/maltodextrin ABC
      transporter comprising a single solute binding domain (MalE) fused to the
      transmembrane subunit MalF.
AB  - Canonical ATP-binding cassette import systems rely on extracellular substrate
      binding proteins (SBP) for function. In gram-negative bacteria, SBPs are usually
      freely diffusible in the periplasm and, where studied, exist in excess over their
      cognate transporters. However, in vitro studies with the maltose transporter of
      Escherichia coli (MalFGK2) have demonstrated that mechanistically one copy of its
      SBP (MalE) per transport complex is sufficient for activity. To address whether
      such a condition is physiologically relevant, we have characterized a homolog of
      the E. coli system from the gram-negative bacterium Bdellovibrio bacteriovorus
      which has a single copy of a maltose binding domain fused to the MalF subunit.
      Both transporters share substrate specificity for maltose and linear
      maltodextrins. Specific ATPase and transport activities of the B. bacteriovorus
      transporter were comparable to those of the E. coli system assayed at a 1:1 M
      ratio of MalE to the transport complex. While MalEEc was able to additionally
      increase ATPase activity of MalFGK2Bb, the isolated MalE domain of B.
      bacteriovorus failed to stimulate the E. coli system. Strikingly, interactions of
      the MalE domain with the transmembrane subunits during the transport cycle as
      studied by site-specific cross-linking were found to differ from those observed
      for E. coli MalE-FGK2.

PMID- 30193863
TI  - HIV drug resistance in low-income and middle-income countries.
AB  - After 15 years of global scale-up of antiretroviral therapy (ART), rising
      prevalence of HIV drug resistance in many low-income and middle-income countries
      (LMICs) poses a growing threat to the HIV response, with the potential to drive
      an increase in mortality, HIV incidence, and costs. To achieve UNAIDS global
      targets, enhanced strategies are needed to improve quality of ART services and
      durability of available ART regimens, and to curb resistance. These strategies
      include roll out of drugs with greater efficacy and higher genetic barriers to
      resistance than those that are currently widely used, universal access to and
      improved effectiveness of viral load monitoring, patient-centred care delivery
      models, and reliable drug supply chains, in conjunction with frameworks for
      resistance monitoring and prevention. In this Review, we assess contemporary data
      on HIV drug resistance in LMICs and their implications for the HIV response,
      highlighting the potential impact and resistance risks of novel ART strategies
      and knowledge gaps.

PMID- 30193864
TI  - The mechanism of action of a fat regulator: Glycyrrhetinic acid (GA) stimulating
      fatty acid transmembrane and intracellular transport in blunt snout bream
      (Megalobrama amblycephala).
AB  - High-fat diets are associated with fatty liver and aberrant hepatic lipid
      metabolism, and glycyrrhetinic acid (GA) has been shown to exert a beneficial
      effect on lipolysis and fat deposition in fish. In the present study, we
      evaluated the effect of GA on the growth performance and expression of hepatic
      lipid transport related genes in blunt snout bream (Megalobrama amblycephala) fed
      a high fat diet. Two hundred and sixteen fish (average body weight: 45.57 g +/-
      0.98 g) were fed three experimental diets (6% fat/L6 group, control, 11% fat/L11
      group, and 11% fat with 0.3 mg kg-1 GA/L11GA group) for 8 weeks. Compared to the
      control group, the weight gain and specific growth rate of high-fat fed group at
      the end of the trialwere significantly improved (P < .05).However, GA showed no
      effect on animals' growth performance(P > .05). Dietary supplementation with 0.3
      mg kg-1 GA significantly decreased the hepatosomatic index, viscera/body ratio,
      and intraperitoneal fat ratio (P < .05), and up-regulated the expression levels
      of fatty acids transport protein (FATP), fatty acids binding protein (FABP),
      fatty acid translocase (CD36), carnitine palmitoyl transferase I (CPT1) and
      peroxisome proliferators-activated receptors alpha (PPARalpha) compared to both
      the L6 group and L11 group (P < .05). However, no significant difference was
      observed in fatty acid synthetase (FAS), acetyl-CoA carboxylase alpha (ACCalpha),
      or lipoprotein lipase (LPL) between groups (P > .05). In conclusion, GA
      significantly rescued high-fat diet induced hepatic lipid accumulation and
      metabolism dysfunction in M. amblycephalaby stimulating hepatic fatty acid
      transport and beta-oxidation. Dietary GA may be used as a promising supplement to
      alleviate high-fat diet induced side effects on M. amblycephala.

PMID- 30193865
TI  - Salvianolic acid B as an anti-emphysema agent II: In vivo reversal activities in
      two rat models of emphysema.
AB  - Emphysema progressively destroys alveolar structures, leading to disability and
      death, yet remains irreversible and incurable to date. Impaired vascular
      endothelial growth factor (VEGF) signaling is an emerging pathogenic mechanism,
      thereby proposing a hypothesis that VEGF stimulation/elevation enables recovery
      from alveolar structural destruction and loss of emphysema. Our previous in vitro
      study identified that salvianolic acid B (Sal-B), a polyphenol of traditional
      Chinese herbal danshen, stimulated lung cell proliferation and migration, and
      protected against induced lung cell death, by virtue of signal transducer and
      activator of transcription 3 (STAT3) activation and VEGF stimulation/elevation.
      Thus, this study examined Sal-B for in vivo therapeutic reversal of established
      emphysema in two rat models. Emphysema was induced with porcine pancreatic
      elastase (PPE) and cigarette smoke extract (CSE), and established by day 21. Sal
      B was then spray-dosed to the lung three times weekly for three weeks. Functional
      treadmill exercise endurance; morphological airspace enlargement and alveolar
      destruction; apoptosis, cell proliferation and tissue matrix proteins;
      phosphorylated STAT3 (pSTAT3) and VEGF expressions; neutrophil accumulation; and
      lipid peroxidation were determined. In both models, Sal-B at 0.2 mg/kg
      significantly reversed impaired exercise endurance by 80 and 64%; airspace
      enlargement [mean linear intercept (MLI)] by 56 and 67%; and alveolar destructive
      index (%DI) by 63 and 66%, respectively. Induced apoptosis activity [cleaved
      caspase-3] was normalized by 94 and 82%; and cell proliferation activity
      [proliferative cell nuclear antigen (PCNA)] was stimulated by 1.6 and 2.1-fold.
      In the PPE-induced model, Sal-B reduced induction of lung's matrix
      metalloproteinase (MMP)-9 and MMP-2 activities by 59 and 94%, respectively, and
      restored pSTAT3 and VEGF expressions to the healthy lung levels, while leaving
      neutrophil accumulation unchecked [myeloperoxidase (MPO) activity]. In the CSE
      induced model, Sal-B elevated pSTAT3 and VEGF expressions both by 1.8-fold over
      the healthy lung levels, and normalized induced lipid peroxidation
      [malondialdehyde (MDA) activity] by 68%. These results provide an in vivo proof
      of-concept for Sal-B as one of the first anti-emphysema agents enabling reversal
      of alveolar structural destruction and loss via local lung treatment by virtue of
      its STAT3 activation and VEGF stimulation.

PMID- 30193866
TI  - Pharmacological approach and adherence to treatment recommendations in frequently
      and non-frequently exacerbating COPD patients from Italy: MISTRAL - The
      prospective cohort, observational study.
AB  - BACKGROUND: Several documents and guidelines provide recommendations for
      effective management of COPD patients. However, there is often a significant
      imbalance between recommended treatment of COPD patients and the actual care
      provided both in primary care and specialty setting. This imbalance could result
      in a significant negative impact on patients' health status and quality of life,
      leading to increased hospitalisations and health resource utilisation in COPD
      patients METHODS: MISTRAL was an observational, longitudinal, prospective cohort
      study, designed to assess the overall pharmacological approach of COPD in routine
      clinical practice in Italy. Eligible patients were divided into two cohorts based
      on their exacerbation history in the year prior to the enrolment, frequent
      exacerbators (FEs; >=2 exacerbations), and non-frequent exacerbators (NFEs; <=1
      exacerbation). The primary objective was to assess adherence to Global Initiative
      for Chronic Obstructive Lung Disease (GOLD) 2011 treatment recommendations in FEs
      and NFEs at baseline and follow-up visits RESULTS: Of the 1489 enrolled patients,
      1468 (98.6%; FEs, 526; NFEs, 942) were considered evaluable for analyses. At
      baseline, 57.8% of patients were treated according to GOLD 2011 recommendations;
      a greater proportion of FEs were treated according to GOLD recommendations,
      compared with NFEs patients at baseline (77.1% versus 46.7%; P < 0.0001), and all
      study visits. At baseline, GOLD group D patients were the most adherent (81.2%)
      to treatment recommendations, while group A patients were the least adherent
      (30.3%) at baseline, attributed mainly to overuse of inhaled corticosteroids in
      less severe GOLD groups. Triple therapy with long-acting muscarinic antagonist
      (LAMA) + long-acting beta2-agonist/inhaled corticosteroid (LABA/ICS) was the most
      frequent prescribed treatment at all study visits, irrespective of patient's
      exacerbation history. Changes in treatment were more frequent in FEs versus NFEs
      CONCLUSIONS: The Mistral study reports a scarce adherence to the GOLD 2011
      treatment recommendations in routine clinical practice in Italy. The adherence
      was particularly low in less severe, non-frequent exacerbating patients mostly
      for ICS overuse, and was higher in high-risk, frequent exacerbating COPD
      patients.

PMID- 30193867
TI  - Comorbidities of IPF: How do they impact on prognosis.
AB  - Idiopathic Pulmonary Fibrosis (IPF) is a severe parenchymal lung disease
      characterized by an intense deposition of collagen in the interstitial spaces.
      The introduction of anti-fibrotic drugs increased patients' life expectancy
      highlighting the role of comorbidities in patients' management and prognosis. IPF
      is frequently associated with other diseases mainly because of its onset during
      middle age and sometimes because of the presence of common pathogenic pathways
      such as in the case of lung cancer. Comorbidities may differently influence
      prognosis of IPF patients. However, except for major impacting ones as LC, PH and
      cardiovascular diseases, data exploring their impact on prognosis are still few
      and sometimes conflicting highlighting the need of new large and targeted
      studies. In this review we discuss the current knowledge on the most common
      comorbidities associated with IPF (cardiovascular diseases, pulmonary
      hypertension, lung cancer, emphysema, gastro-oesophageal reflux and depression),
      focusing on their prognostic role.

PMID- 30193868
TI  - Embracing the new vulnerable self: A grounded theory approach on critical care
      survivors' post-intensive care syndrome.
AB  - OBJECTIVES: This study explored critical care survivors' experience of post
      intensive care syndrome. RESEARCH DESIGN AND SETTING: This qualitative study
      employed a classic grounded theory approach with 13 survivors after intensive
      care unit treatment. MAIN OUTCOME MEASURES: Data were collected through one-to
      one in-depth interviews. Open, axial and selective coding were performed based on
      interview transcripts, field notes, and memos. FINDINGS: The analysis of
      survivors' experience with post-intensive care syndrome led to the 'embracing the
      new vulnerable self' theory. After discharge from the intensive care, survivors
      became physically, psychologically, cognitively and socially vulnerable. The
      survivors were struggling for recovery; they faced new crises and some were
      devastated. However, their internal and external resources helped them recover.
      Through coping processes, survivors gained a new perspective on normality.
      CONCLUSION: These results contribute to understanding the post-intensive care
      syndrome phenomenon and coping process of critical care survivors. This syndromes
      is a multidimensional phenomenon and the recovery process is a continuum. An
      integrated rehabilitation program that extends beyond utilising family support
      requires development.

PMID- 30193869
TI  - Importance of TLR9-IL23-IL17 axis in inflammatory bowel disease development: Gene
      expression profiling study.
AB  - BACKGROUND AND AIMS: Mucosal gene expression have not been fully enlightened in
      inflammatory bowel disease (IBD). Aim of this study was to define IL23A, IL17A,
      IL17F and TLR9 expression in different IBD phenotypes. METHODS: Evaluation of
      mRNA levels was performed in paired non-inflamed and inflamed mucosal biopsies of
      newly diagnosed 50 Crohn's disease (CD) and 54 ulcerative colitis (UC) patients
      by quantitative real-time PCR analysis. RESULTS: IL17A and IL17F expression
      levels were significantly increased in inflamed IBD mucosa. Inflamed CD ileal and
      UC mucosa showed increased IL23A, while only inflamed CD ileal samples showed
      increased TLR9 mRNA level. Correlation between analysed mRNAs levels and
      endoscopic and clinical disease activity were found in UC, but only with clinical
      activity in CD. CONCLUSION: Both CD and UC presented expression of Th17
      associated genes. Nevertheless, expression profiles between different disease
      forms varies which should be taken into account for future research and
      therapeutics strategies.

PMID- 30193870
TI  - Office hysteroscopy for postmenopausal women: Feasibility and correlation with
      transvaginal ultrasound.
AB  - OBJECTIVE: To evaluate feasibility of office hysteroscopy in postmenopausal women
      and correlation between transvaginal ultrasound (TV-US) and hysteroscopy.
      METHODS: Postmenopausal women addressed at office hysteroscopy for postmenopausal
      bleeding or increase endometrial thickness were included. A 3.5-mm rigid
      hysteroscope was used without cervical dilatation or local anaesthesia. Speculum
      was never used. Data concerning women's symptoms and TV-US findings were
      collected. RESULTS: Four-hundred-seventy postmenopausal women referred for office
      hysteroscopy were included in this descriptive study. Three-hundred-fifty women
      (74.5%) experienced abnormal uterine bleeding. The success rate of office
      hysteroscopy was 76.4% and was significantly higher in cases of postmenopausal
      bleeding (80.9%) than in women without postmenopausal bleeding (63.3%) (p=0.01).
      Three-hundred-sixteen women had both a successful hysteroscopy and TV-US. The
      correlation between hysteroscopy and TV-US was 68.5% for the diagnosis of
      increased endometrial thickness, polyps and submucosal myoma (Kappa=0.28). The
      rate of endometrial cancer for women with postmenopausal bleeding was 12.6%
      (n=44) while it was 1.7% (n=2) for asymptomatic women. Two (4.3%) out of these 46
      women with endometrial cancer had normal hysteroscopy, while 7 (15.2%) had a
      normal TV-US (including endometrial thickness below 5mm). Among the 54 women
      without bleeding and with a thickened endometrium, one (1.8%) had endometrial
      cancer. CONCLUSION: Office hysteroscopy is successful without anaesthesia for
      76.4% of postmenopausal women. The correlation between TV-US and hysteroscopy is
      low, and we recommend to practice both sonography and hysteroscopy in women with
      postmenopausal bleeding.

PMID- 30193871
TI  - Trabecular bone score in adults with cerebral palsy.
AB  - CONTEXT: Bone fragility in cerebral palsy (CP) is secondary to a complex
      interplay of functional, hormonal, and nutritional factors that affect bone
      remodelling. A greater understanding of bone microarchitectural changes seen in
      CP should assist therapeutic decision making. OBJECTIVE: To examine the
      relationship between trabecular bone score (TBS), BMD and fractures in adults
      with CP; the influence of clinical factors and body composition on bone
      microarchitecture were explored. DESIGN: Retrospective cross-sectional study.
      SETTING AND PARTICIPANTS: 43 adults (25 male) with CP of median age 25 years
      (interquartile range 21.4-33.9) who had evaluable dual-energy X-ray
      absorptiometry imaging of the lumbar spine from a single tertiary hospital
      between 2005-March 2018. RESULTS: 24/43 (55.8%) of patients had TBS values
      indicating intermediate or high risk of fracture (<1.31). TBS correlated with
      areal BMD at the lumbar spine, femoral neck and total body. TBS was significantly
      associated with arm and leg lean mass, with adjustment for age, gender and height
      (adjusted R2 = 0.18, p = 0.042 for arm lean mass; adjusted R2 = 0.19, p = 0.036
      for leg lean mass). There was no difference in TBS when patients were grouped by
      fracture status, anticonvulsant use, gonadal status or use of PEG feeding. TBS
      was lower in non-ambulatory patients compared with ambulatory patients (1.28 vs
      1.37, p = 0.019). CONCLUSIONS: Abnormal bone microarchitecture, as measured by
      TBS, was seen in >50% of young adults with CP. TBS correlated with both areal BMD
      and appendicular lean mass. Maintaining muscle function is likely to be important
      for bone health in young adults with CP and needs to be confirmed in further
      studies.

PMID- 30193872
TI  - Statistically but not clinically significant? Biomarkers in gastric cancer.

PMID- 30193873
TI  - Isolated colonic Crohn's disease is associated with a reduced response to
      exclusive enteral nutrition compared to ileal or ileocolonic disease.
AB  - BACKGROUND & AIMS: Exclusive enteral nutrition (EEN) as a primary therapy is safe
      and effective for inducing the clinical remission of active luminal Crohn's
      disease (CD). Whether isolated colonic involvement affects the efficacy of EEN is
      controversial. We aimed to identify the influence of isolated colonic CD on the
      efficacy of EEN and to determine other potential predictors of the response to
      induction therapy with EEN in adult patients with CD. METHODS: Data for adult CD
      patients treated with EEN as an induction therapy at our centre from January 1,
      2014, to May 31, 2017, were reviewed. Eligible patients were divided into an
      isolated colonic Crohn's disease (cCD) group and a non-isolated colonic Crohn's
      disease (non-cCD) group according to the disease location. The rates of clinical
      remission and inflammatory and nutritional serum markers were compared between
      the groups. Possible relationships between isolated colonic involvement or other
      potential factors and the efficacy of EEN were assessed by univariate and
      multivariate analyses. The propensity score matching method was used to confirm
      the results. RESULTS: Overall, 241 patients were included in the analysis: 52
      patients in the cCD group and 189 patients in the non-cCD group. The rates of
      clinical remission differed between the two groups (cCD group: 51.9% versus non
      cCD group: 68.3%, P = 0.029). Multivariate analyses indicated that isolated
      colonic involvement was associated with a reduced response to EEN (OR = 2.74;
      [CI] 95% = [1.2-6.23], P = 0.016). Additionally, the lean body mass index (LBMI)
      before treatment was associated with the efficacy of EEN (OR = 0.636; [CI] 95% =
      [0.444-0.912], P = 0.014). These associations were confirmed using the propensity
      score model. For patients with isolated colonic CD, multivariate analysis showed
      that pancolitis (OR = 16.7; [CI] 95% = [1.074-260.5], P = 0.044) was another
      independent factor for the efficacy of EEN. Further analysis showed that even in
      patients who achieved clinical remission after EEN, inflammatory serum markers
      declined more slowly in the cCD group than in the non-cCD group, and the time to
      remission was longer in the cCD group. CONCLUSIONS: Isolated colonic CD showed a
      reduced response to induction therapy with EEN compared with ileal or ileocolonic
      disease in adult patients. Patients with isolated colonic CD required more time
      to benefit from EEN therapy compared with patients with non-colonic CD.
      Additionally, LBMI before treatment was associated with the efficacy of EEN.

PMID- 30193874
TI  - Is adequate enteral nutrition associated with a similar outcome as adequate oral
      caloric intake after allogeneic transplantation?

PMID- 30193875
TI  - High iodine dietary intake is associated with type 2 diabetes among women of the
      E3N-EPIC cohort study.
AB  - BACKGROUND: Iodine is an essential micronutrient needed for the production of
      thyroid hormones. Consequently, iodine insufficient and excessive intakes are
      associated with thyroid disorders. Despite the increase in diabetes prevalence
      worldwide and the close relationship between thyroid function and the risk of
      diabetes, the relationship between iodine intake and diabetes has been
      overlooked. The objective of the present study is to investigate the link between
      iodine intake and the risk of type 2 diabetes. METHODS: Cox proportional hazards
      regression models adjusted on potential confounders were used to calculate the
      hazard ratios and 95% confidence intervals for the associations between dietary
      iodine intake and type 2 diabetes risk among 71,264 women of the E3N-EPIC cohort.
      RESULTS: The average iodine intake in the study population was 155.6 MUg/day (+/
      47.1 MUg/day). After adjusting for the main risk factors for diabetes, for
      hypo/hyperthyroidism, as well as for phosphorus intakes and consumption of dairy
      products and seafood, the hazard ratios (95% CI) for type 2 diabetes of women in
      the 4th (160.7-190.5 MUg/day) and 5th (190.6-596.8 MUg/day) quintiles groups of
      iodine intake were 1.27 (1.10-1.47) and 1.28 (1.07-1.53), respectively, compared
      to women with iodine intake below the 1st quintile (29.3-116.9 MUg/day).
      CONCLUSION: This is the first study to investigate the relationship between
      dietary iodine intake and the risk of developing type 2 diabetes. More studies
      are warranted to further investigate the health effects of chronic high iodine
      intake, and in particular to investigate the biological mechanisms that underlie
      the association between iodine intake and type 2 diabetes.

PMID- 30193876
TI  - MicroRNA-125b mimic inhibits ischemia reperfusion-induced neuroinflammation and
      aberrant p53 apoptotic signalling activation through targeting TP53INP1.
AB  - BACKGROUND: Ischemia reperfusion (IR) injury affects neuronal function through
      multiple pathogeneses that induce neuroinflammation and cellular apoptosis. The
      important roles of microRNAs (miRs) in the regulation of spinal cord IR have been
      recently reported. Among these roles, we investigated whether miR-125b and its
      downstream targets regulated the p53 signalling network and participated in both
      inflammation and apoptosis. METHODS: An IR model was established via 12-min
      occlusion of the aortic arch. The direct interaction between miR-125b and
      TP53INP1 was demonstrated by Western blotting and luciferase assays. The cellular
      distributions of TP53INP1 were visualised by double immunofluorescence labelling.
      The effects of miR-125b on the expression of TP53INP1, p53 and release of
      proinflammatory cytokines were evaluated by synthetic miRs. Additionally, the
      detection of hind-limb motor function in vivo and motor neuronal apoptosis in
      vitro were evaluated to explore the potential mechanisms. RESULTS: IR-induced
      alterations in hind-limb motor function were closely related to the temporal
      changes in miR-125b and TP53INP1 expression. The miR-125b/TP53INP1 gene pair was
      confirmed by luciferase assay. Compared with Sham controls, IR treatment resulted
      in increased TP53INP1 immunoreactivity that was primarily distributed in neurons.
      Treatment with miR-125b mimic markedly decreased the protein levels of TP53INP1,
      p53 and cytokines interleukin (IL)-1beta and tumour necrosis factor (TNF)-alpha,
      whereas miR-125b control or inhibitor did not have the above-mentioned effects.
      Moreover, miR-125b mimic improved motor function in vivo and attenuated neuronal
      apoptosis in vitro, as demonstrated by the increased average Tarlov scores in
      lower limbs and lower percentages of neurons in the A4 and A2 quadrants of flow
      cytometry. Fluorescent staining and quantification further indicated that miR
      125b mimic decreased the immunoreactivities of p53 and cleaved caspase 3 in
      neurons and simultaneously reduced the number of double-labelled cells with
      TP53INP1. CONCLUSIONS: miR-125b mimic partially protected neurons against
      neuroinflammation and aberrant p53 network activation-induced apoptosis during IR
      injury through downregulation of TP53INP1.

PMID- 30193877
TI  - Palmitoylethanolamide counteracts autistic-like behaviours in BTBR T+tf/J mice:
      Contribution of central and peripheral mechanisms.
AB  - Autism spectrum disorders (ASD) are a group of heterogeneous neurodevelopmental
      conditions characterized by impaired social interaction, and repetitive
      stereotyped behaviours. Interestingly, functional and inflammatory
      gastrointestinal diseases are often reported as a comorbidity in ASDs, indicating
      gut-brain axis as a novel emerging approach. Recently, a central role for
      peroxisome-proliferator activated receptor (PPAR)-alpha has been addressed in
      neurological functions, associated with the behaviour. Among endogenous lipids,
      palmitoylethanolamide (PEA), a PPAR-alpha agonist, has been extensively studied
      for its anti-inflammatory effects both at central and peripheral level. Based on
      this background, the aim of this study was to investigate the pharmacological
      effects of PEA on autistic-like behaviour of BTBR T+tf/J mice and to shed light
      on the contributing mechanisms. Our results showed that PEA reverted the altered
      behavioural phenotype of BTBR mice, and this effect was contingent to PPAR-alpha
      activation. Moreover, PEA was able to restore hippocampal BDNF signalling
      pathway, and improve mitochondrial dysfunction, both pathological aspects, known
      to be consistently associated with ASDs. Furthermore, PEA reduced the overall
      inflammatory state of BTBR mice, reducing the expression of pro-inflammatory
      cytokines at hippocampal, serum, and colonic level. The analysis of gut
      permeability and the expression of colonic tight junctions showed a reduction of
      leaky gut in PEA-treated BTBR mice. This finding together with PEA effect on gut
      microbiota composition suggests an involvement of microbiota-gut-brain axis. In
      conclusion, our results demonstrated a therapeutic potential of PEA in limiting
      ASD symptoms, through its pleiotropic mechanism of action, supporting
      neuroprotection, anti-inflammatory effects, and the modulation of gut-brain axis.

PMID- 30193878
TI  - Does retching matter? Reviewing the evidence-Physiology and forces.
AB  - Failure of antireflux surgery is common in children with neurodisability, with a
      high incidence of persistent or recurrent symptoms, including retching.
      Anatomical disruption of the wrap is a frequent finding, but what forces underlie
      this disruption? This article reviews the forces generated during potential wrap
      stressing episodes, putting them into the clinical context of wrap failure.
      Historically, wrap failure has been attributed to pressures arising from a
      reduction in gastric capacity or compliance, with advocates for an additional,
      gastric emptying procedure, at the time of fundoplication. However, any
      postoperative pressure changes are small and insufficient to cause disruption,
      and evidence of benefit from gastric emptying procedures is lacking.
      Diaphragmatic stressor events are common in the presence of neurodisability, and
      there is now increasing recognition of an association between diaphragmatic
      stressors and wrap breakdown. The analysis in this review demonstrates that the
      greatest forces on the fundoplication wrap are those associated with retching and
      vomiting. The direction and magnitude of these forces are sufficient to cause
      wrap herniation into the thorax, and wrap separation. Clinical series confirm
      that retching is consistently and strongly associated with wrap breakdown.
      Retching needs to be addressed if we are to reduce the incidence of wrap failure.
      Level of Evidence V.

PMID- 30193879
TI  - Is anammox a promising treatment process for nitrogen removal from nitrogen-rich
      saline wastewater?
AB  - Rapidly growing discharge of nitrogen-rich saline wastewater has significantly
      affect environment. However, due to the inhibition resulting from high salinity
      on microbes, it is still a challenge to treat nitrogen-rich saline wastewater
      efficiently. Anammox process, as a cost-effective and environment-friendly
      nitrogen removal approach, has shown a potential in treating nitrogen-rich saline
      wastewater. This review is conducted from a critical perspective and provides a
      comprehensive overview on the performance of anammox process treating nitrogen
      rich saline wastewater. Two strategies including freshwater-derived anammox
      bacteria acclimatization and marine anammox bacteria enrichment are evaluated.
      Second, effects resulting from salinity on the performance of anammox reactor,
      the microbial communities and sludge characteristics are discussed. Third,
      salinity-tolerant mechanism of anammox bacteria is analyzed. This review also
      reveals some critical knowledge gaps and future research needs, which benefits
      application of anammox process to treat nitrogen-rich saline wastewater.

PMID- 30193880
TI  - Cross-Validation of Arthroplasty Records Between Arthroplasty and Hospital
      Discharge Registers, Self-Reports, and Medical Records Among a Cohort of 14,220
      Women.
AB  - BACKGROUND: There are no actual validation studies of the Finnish Arthroplasty
      Register (FAR), and only a few studies about the accuracy of self-reported hip
      and knee arthroplasty exist. Therefore, we examine how reliably total hip (THA)
      and knee (TKA) arthroplasties can be identified from multiple data sources,
      including self-reports, the hospital discharge register, the arthroplasty
      register, and medical records. METHODS: Data from the FAR and from the Finnish
      Hospital Discharge Register (FHDR) during the years 1980-2010 were cross-checked
      to identify all THA and TKA events for the Kuopio Osteoporosis Risk Factor and
      Prevention Study cohort (n = 14,220). Unclear events were further checked from
      the medical records. After establishing a gold standard, by referring to
      confirmed THAs and TKAs, we examined the validity of self-reports in identifying
      the prevalent population with THA/TKA and in identifying incident THA/TKA.
      RESULTS: Completeness of 2820 total arthroplasty events was 96.1% in FAR and
      98.3% in FHDR. The self-reports had 95.1% sensitivity and 92.9% positive
      predictive value (PPV) to identify population with THA and for TKA sensitivity
      was 94.6% and PPV 95.2%. Self-reports' sensitivity of finding the actual surgery
      events was 65.3% and PPV 85.4% for THA and for TKA sensitivity was 62.9% and PPV
      83.4%. CONCLUSION: The best way to identify THAs and TKAs in Finland is to
      combine data from the FAR and the FHDR. Self-reports can be considered as
      suitable to identify the prevalent population with THA/TKA, and they do not work
      as well to identify the actual surgery events.

PMID- 30193881
TI  - Internal Validation of a Predictive Model for Complications After Total Hip
      Arthroplasty.
AB  - BACKGROUND: Total hip arthroplasty (THA) is projected to increase in prevalence
      and associated complications will impose significant cost on the US healthcare
      system. The purpose of this study is to validate a predictive model for
      postoperative complications utilizing a novel 11-component hip-specific
      questionnaire encompassing preoperatively available clinical and radiographic
      data. METHODS: Consecutive primary THA patients between January 2014 and January
      2016 were included. Exclusion criteria included patients without questionnaire
      scoring variables and less than 1-year follow-up. Patients were stratified into 4
      tiers based on their questionnaire score: low risk (>74), mild risk (57-73),
      moderate risk (41-56), and high risk (<40). A binary logistic regression was
      performed to determine if the questionnaire predicted complications. Receiver
      operator curves were constructed to determine the threshold score below which
      there was a high likelihood of experiencing a complication. RESULTS: Four hundred
      fifty patients were included in the final analysis with a mean (range) follow-up
      of 2.1 years (1.0-5.9), age of 63.1 years (25.7-9.17), and body mass index of
      31.7 kg/m2 (17.8-64.5). The complication rate was 13.6%. A hip questionnaire
      score of 73.8 conferred a 98.5% sensitivity and 98.5% negative predictive value
      for complications. The questionnaire score was the strongest predictor of a
      decreased complication likelihood (odds ratio 0.94, 95% confidence interval 0.90
      0.97, P < .001). Risk tier was significantly associated with complications (low
      risk: 0; mild risk: 12; moderate risk: 25; and high risk: 24; P < .001).
      CONCLUSION: This novel hip questionnaire demonstrated a high sensitivity and
      negative predictive value to identify patients at risk for postoperative
      complications. Future studies should attempt to prospectively validate the use of
      this questionnaire.

PMID- 30193882
TI  - Managing Prolonged Pain After Surgery: Examining the Role of Opioids.
AB  - A notable minority of patients experience persistent postsurgical pain and some
      of these patients consequently have prolonged exposure to opioids. Risk factors
      for prolonged opioid use after surgery include preoperative opioid use, anxiety,
      substance abuse, and alcohol abuse. The window to intervene and potentially
      prevent persistent opioid use after surgery is short and may best be accomplished
      by both surgeon and anesthesiologist working together. Anesthesiologists in
      particular are well positioned in the perioperative surgical home model to affect
      multiple aspects of the perioperative experience, including tailoring
      intraoperative medications and providing consultation for possible discharge
      analgesic regimens that can help minimize opioid use. Multimodal analgesia
      protocols reduce opioid consumption and thereby reduce exposure to opioids and
      theoretically the risk of persistent use. Regional anesthesia and analgesia
      techniques also reduce opioid consumption. Although many patients will recover
      without difficulty, the small minority who do not should receive customized care
      which may involve multiple office visits or consultation of a pain specialist.
      Enhanced recovery pathways are useful in optimizing outcomes after surgery.

PMID- 30193883
TI  - Effects of a Community Outreach Program for Maternal Health and Family Planning
      in Tigray, Ethiopia.
AB  - PURPOSE: We examined the effects of a community outreach program for maternal
      health in Tigray, Ethiopia, on women's knowledge about pregnancy, childbirth,
      postpartum care, and family planning, and assessed their participation in
      antenatal care, postpartum checkups, institutional childbirth, and contraceptive
      use. METHODS: We recruited Ethiopian women of reproductive age (15 to 49 years)
      in Tigray, Ethiopia. Two villages in Tigray, Kihen and Mesanu, which have similar
      population sizes and living environments, were chosen as the intervention and
      comparison groups, respectively. A two-group pretest-posttest design with cluster
      sampling was employed. We conducted self-report questionnaire surveys using face
      to-face interviews. The 2.5-year community outreach program was developed based
      on Rogers' diffusion of innovation theory. It consisted of mass media use and
      health education for lay women in the community, along with training of health
      care providers, including nurses, midwives, and health extension workers, in
      maternal health care. RESULTS: The intervention group showed significant
      increases in knowledge and behaviors regarding maternal health and family
      planning compared to the comparison group (p < .001). In particular, there was a
      dramatic increase from 10.8% to 93.5% in the institutional birth rate in the
      intervention group. CONCLUSION: The community outreach program and health care
      professional training effectively improved knowledge and behaviors regarding
      maternal health in Ethiopian women. Mass media and interpersonal communication
      channels for health education may be useful health interventions in developing
      countries.

PMID- 30193884
TI  - Handgrip Strength and Its Associated Factors among Community-dwelling Elderly in
      Sri Lanka: A Cross-sectional Study.
AB  - PURPOSE: Low muscle strength is central to geriatric physical disabilities and
      mortality. The purpose of the present study was to examine handgrip strength
      (HGS) and its associated factors among community-dwelling older people in Sri
      Lanka. METHODS: A cross-sectional study was conducted in the Kandy district using
      multistage sampling. A total of 999 older people were recruited, with a female
      preponderance. Data were collected using interviewer-administered questionnaires
      on demographic characteristics, depression, and physical activity. Anthropometric
      measurements including weight, height, mid-upper arm circumference, calf
      circumference, and HGS were recorded. Complex sample general linear model was
      used to examine the association between HGS and its associated factors. RESULTS:
      The mean highest HGS of the study group was 12.56 kg (95% confidence interval:
      11.94-13.19). Male older people had a higher HGS (17.02, 95% confidence interval:
      15.55-18.49 kg) than females (10.59, 95% confidence interval: 10.12-11.06 kg).
      For both men and women, older age was associated with lower HGS, while mid-upper
      arm circumference was associated with better HGS. Diabetes mellitus, vegetarian
      diet, and alcohol consumption were associated with HGS for women only.
      CONCLUSION: Men had a higher HGS compared with women. Age, mid-upper arm
      circumference, diabetes mellitus, vegetarian diet, and alcohol consumption were
      factors associated with HGS among community-dwelling older people in Kandy
      district, Sri Lanka. HGS can be used as a feasible strategy to improve health
      status of older people by community health nurses.

PMID- 30193885
TI  - Analysis of the effectiveness of training school personnel in the management of
      food allergy and anaphylaxis.
AB  - BACKGROUND: Food allergy is a very frequent and increasingly common disease in
      children and adolescents. It affects quality of life and can even be life
      threatening. Given that 10-18% of allergic/anaphylactic food reactions take place
      in schools, it is essential to provide school personnel with training on the
      management of reactions. METHODS: The Allergy Unit of Hospital Universitario de
      Fuenlabrada, Spain, organized a conference entitled "Management of Food Allergy
      in Children and Adolescents in School Centers" during which teachers, cooks,
      cafeteria monitors, and summer-camp leaders underwent a training course.
      Attendees filled out a questionnaire with eight questions before and after the
      course to assess their self-efficacy in management of food allergy and
      anaphylaxis. The results were compared. RESULTS: A total of 191 people
      participated (51% dining-room monitors, 24% teachers, 13% cooks, and 12% other
      professions). The areas in which the attendees presented the lowest confidence
      before receiving the course were recognition of symptoms and treatment of the
      reactions/anaphylaxis. The mean score for each of the eight concepts evaluated
      improved after the training course. This improvement was significant in the
      management of anaphylaxis. CONCLUSIONS: Our study demonstrates the usefulness of
      a self-efficacy scale in school personnel as a tool to assess the ability to
      manage food allergy and anaphylaxis. It can help to identify problem areas in
      which more specific training programs can be implemented.

PMID- 30193886
TI  - Asthma diagnosis in infants and preschool children: a systematic review of
      clinical guidelines.
AB  - BACKGROUND AND AIM: The definition and diagnosis of asthma are the subject of
      controversy that is particularly intense in the case of individuals in the first
      years of life, due to reasons such as the difficulty of performing objective
      pulmonary function tests or the high frequency with which the symptoms subside in
      the course of childhood. Since there is no consensus regarding the diagnosis of
      asthma in preschool children, a systematic review has been carried out. MATERIALS
      AND METHODS: A systematic search was made of the clinical guidelines published in
      the last 10 years and containing information referred to the concept or diagnosis
      of asthma in childhood - including the first years of life (infants and preschool
      children). A series of key questions were established, and each selected guide
      was analyzed in search of answers to those questions. The review protocol was
      registered in the international prospective register of systematic reviews
      (PROSPERO), with registration number CRD42017074872. RESULTS: Twenty-one clinical
      guidelines were selected: 10 general guides (children and adults), eight
      pediatric guides and three guides focusing on preschool children. The immense
      majority accepted that asthma can be diagnosed from the first years of life,
      without requiring pulmonary function tests or other complementary techniques. The
      response to treatment and the exclusion of other alternative diagnoses are key
      elements for establishing the diagnosis. Only one of the guides denied the
      possibility of diagnosing asthma in preschool children. CONCLUSIONS: There is
      generalized although not unanimous agreement that asthma can be diagnosed in
      preschool children.

PMID- 30193887
TI  - Subdiuretic dose of furosemide enhances albuterol effects in asthmatic mice
      rather than bumetanide.
AB  - BACKGROUND: One of the loop diuretics, furosemide, was found useful in bronchial
      asthma. It enhanced anti-asthmatic effects of albuterol. The underlying mechanism
      is still unclear. OBJECTIVE: This study was planned to investigate whether the
      enhancing effect of furosemide for albuterol in ovalbumin-induced asthmatic
      BALB/c mice is diuretic-related or not. METHODS: Two sets of experiments were
      performed. In the first, effects of inhaled subdiuretic doses of furosemide and
      bumetanide (another loop diuretic) were compared. Treatments (mg/mL) were given
      as 15 minute-inhalation before final ovalbumin provocation as follows: albuterol
      (2.5), furosemide (0.08), bumetanide (0.005), (albuterol+furosemide, 2.5+0.08),
      and (albuterol+bumetanide, 2.5+0.005). Airway hyperreactivity (AHR) to inhaled
      methacholine, levels of IL-6, TNF-alpha, and differential white blood cells in
      bronchoalveolar lavage fluid (BALF), and lung histopathology were evaluated. In
      the second set, effects of oral diuretic doses (mg/kg) of furosemide (10) and
      bumetanide (0.25) were given before final ovalbumin provocation. Urine volume and
      asthma parameters were measured. RESULTS: Ovalbumin-asthmatic mice showed
      significant increases in AHR, levels of IL-6, TNF-alpha, and inflammatory cells
      in BALF, and lung inflammatory cell infiltration. Inhaled furosemide
      significantly decreased these changes while inhaled bumetanide failed. Albuterol
      and albuterol+bumetanide significantly decreased these changes more than
      furosemide while albuterol+furosemide produced the most significant decreases.
      Both oral furosemide and bumetanide exerted equivalent diuretic effects but
      failed to improve asthma. CONCLUSIONS: Inhaled subdiuretic dose of furosemide
      enhanced effects of albuterol more in ovalbumin-asthmatic mice rather than
      bumetanide, while oral diuretic doses of both drugs failed to improve asthma,
      indicating that this enhancing effect is not diuretic-related.

PMID- 30193888
TI  - Detection of profilin in SPT extracts that are supposed to contain it.
AB  - INTRODUCTION AND OBJECTIVES: Profilin is a panallergen contained in pollen, plant
      foods and latex. Although cross-reactivity is expected while performing skin
      prick tests (SPT) with allergens that contain profilin, this is not always
      noticed. The purpose of this study was to detect if profilin is contained in the
      commercial SPT extracts of pollen and plant foods which, in their fresh form,
      contain determined epitopes of profilin. MATERIAL AND METHODS: Commercial SPT
      extracts of different pharmaceuticals were analyzed using sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE). The study included purified palm
      date profilin, peach (whole, pulp and peel extracts), hazelnut, Olea europea,
      Parietaria judaica and Phleum pratense. RESULTS: Profilin was detected in all,
      but peach extracts; it was neither contained in the whole peach extract nor in
      the ones of peel or pulp. CONCLUSION: The only accurate way to detect
      sensitization to profilin, while performing SPT, is the use of purified profilin
      extract. Even if a plant food or pollen contain an identified molecule of
      profilin, the relevant SPT commercial extract may not.

PMID- 30193889
TI  - The profile of IL-4, IL-5, IL-10 and GATA3 in patients with LRBA deficiency and
      CVID with no known monogenic disease: Association with disease severity.
AB  - BACKGROUND: Common variable immunodeficiency (CVID) is the most common
      symptomatic form of primary immunodeficiency (PID). LPS-responsive beige-like
      anchor protein (LRBA) deficiency is an autosomal recessive disease characterized
      by a CVID-like phenotype. T cell abnormality was reported in patients with CVID
      and LRBA deficiency. The study's aim was to evaluate IL-4, IL-5, IL-10 and GATA3
      expression in patients with LRBA deficiency and CVID with no known monogenic
      disease, and further evaluate its relevance with immunological futures and
      clinical complications of patients. METHODS: The study population comprised
      patients with CVID, LRBA deficiency and age-sex matched healthy controls.
      Mutation analysis was done by whole exome sequencing in CVID patients to rule out
      monogenic PIDs. After CD4+ T cell stimulation with anti-CD3 and anti-CD28
      monoclonal antibodies, gene expression of IL-4, IL-5, IL-10 and transcription
      factor GATA3 was evaluated by real-time polymerase chain reaction. The protein of
      mentioned cytokines was assessed by enzyme-linked immunosorbent assay. RESULTS:
      The main clinical presentations of CVID patients were infections only and
      lymphoproliferations phenotypes, but in LRBA patients were autoimmune and
      enteropathy phenotype. The frequencies of CD4+ T cells were significantly reduced
      in LRBA and CVID patients. There were no statistically significant differences
      among GATA3, IL4, and IL5 gene expressions by CD4+ T cells of patients and
      controls, however, the IL10 expressions in CVID patients was significantly lower
      than in LRBA patients and HCs. As compared with HCs, CVID patients showed a
      prominent decrease in IL-4 and IL-10 production by CD4+ T cells. CONCLUSIONS: Our
      findings demonstrated that patients with CVID and LRBA deficiency (even with
      severe infectious and inflammatory complications) have not imbalance in Th2
      response, which is in parallel with lower frequency of allergy and asthma in
      these patients.

PMID- 30193890
TI  - Contact sensitization in children with atopic dermatitis.
AB  - BACKGROUND: Atopic dermatitis is a common illness in childhood. Children with
      atopic dermatitis are prone to develop cutaneous sensitization due to skin
      barrier dysfunction. AIM: The aim of this study was to evaluate the frequency of
      cutaneous sensitizations in patients with atopic dermatitis and to identify the
      most frequent causative allergens. STUDY DESIGN: The study group consisted of 112
      children with atopic dermatitis, aged 1-18 years (median 88.5 months) and 39
      healthy controls, aged 1-8 years (median 88.48 months). METHODS: The diagnosis of
      atopic dermatitis was established by modified Hanifin and Rajka criteria;
      severity of the disease was assessed by scoring of atopic dermatitis. Serum blood
      eosinophil count, total IgE and skin prick tests for common aeroallergens and
      food allergens were performed. Patch tests with cosmetic series and European
      standard patch test series (Stallegenes(c) Ltd, Paris, France) were applied.
      RESULTS: Of the children with atopic dermatitis, 17% (n=19) were sensitized to
      either cosmetic or standard series or both of them; no children in the control
      group had a positive patch test (p=0.001). Atopy and severity of atopic
      dermatitis was not a significant risk factor for cutaneous sensitization. The
      most common allergens were Nickel sulphate and Methychloroisothiazinolone (4.5%
      and 4.5%) in the European standard patch test and cocamidoproplybetaine (12.5%)
      in the cosmetic series patch test. CONCLUSION: Cutaneous sensitization can
      develop in children with atopic dermatitis, therefore allergic contact dermatitis
      should be kept in mind.

PMID- 30193891
TI  - MnSOD mediates shear stress-promoted tumor cell migration and adhesion.
AB  - Circulation of cancer cells in the bloodstream is a vital step for distant
      metastasis, during which cancer cells are exposed to hemodynamic shear stress
      (SS). The actions of SS on tumor cells are complicated and not fully understood.
      We previously reported that fluidic SS was able to promote migration of breast
      cancer cells by elevating the cellular ROS level. In this study, we further
      investigated the mechanisms regulating SS-promoted cell migration and identified
      the role of MnSOD in the related pathway. We found that SS could enhance tumor
      cell adhesion to extracellular matrix and endothelial monolayer, and MnSOD also
      regulated this process. Briefly, SS stimulates the generation of mitochondrial
      superoxide in tumor cells. MnSOD then converts superoxide into hydrogen peroxide,
      which activates ERK1/2 to promote tumor cell migration and activates FAK to
      promote tumor cell adhesion. Combining our previous and present studies, we
      present experimental evidence on the pro-metastatic effects of hemodynamic SS and
      reveal the underlying mechanism. Our findings provide new insights into the
      nature of cancer metastasis and the understanding of tumor cell responses to
      external stresses and have valuable implications for cancer therapy development.

PMID- 30193892
TI  - Oxidative stress and mitochondrial dysfunction in parafacial respiratory group
      induced by maternal cigarette smoke exposure in rat offspring.
AB  - Cigarette smoke (CS) exposure negatively affects neurodevelopment. We established
      a CS exposure rat model to determine how maternal CS exposure induces oxidative
      stress and mitochondrial dysfunction in parafacial respiratory group (pFRG)
      essential to central chemoreceptive regulation of normal breathing. Pregnant rats
      were exposed to CS during gestational days 1-20, and the offspring were studied
      on postnatal day 2. Our data showed that maternal CS exposure resulted in
      elevated accumulation of ROS, which left a footprint on DNA and lipid with
      increases in 8-hydroxy-2'-deoxyguanosine and malondialdehyde contents.
      Furthermore, maternal CS exposure induced decreases in manganese superoxide
      dismutase, catalase and glutathione reductase activities as well as reduction in
      glutathione content in pFRG in the offspring. Moreover, maternal exposure to CS
      led to mitochondrial ultrastructure changes, mitochondrial swelling, reduction in
      ATP generation, loss of mitochondrial membrane potential and increase in
      mitochondrial DNA copy number. These findings suggest that maternal exposure to
      CS alters normal development of pFRG that is critical for normal respiratory
      control.

PMID- 30193893
TI  - miR-324-5p is up regulated in end-stage osteoarthritis and regulates Indian
      Hedgehog signalling by differing mechanisms in human and mouse.
AB  - The Hedgehog (Hh) signalling pathway plays important roles during embryonic
      development and in adult tissue homeostasis, for example cartilage, where its
      deregulation can lead to osteoarthritis (OA). microRNAs (miRNAs) are important
      regulators of gene expression, and have been implicated in the regulation of
      signalling pathways, including Hh, thereby impacting upon development and
      disease. Our aim was to identify the function of miRNAs whose expression is
      altered in OA cartilage. Here we identified an increase in miR-324-5p expression
      in OA cartilage and hypothesised that, as in glioma, miR-324-5p would regulate Hh
      signalling. We determined that miR-324-5p regulates osteogenesis in human
      mesenchymal stem cells (MSCs) and in mouse C3H10T1/2 cells. Luciferase reporter
      assays demonstrated that miR-324-5p directly regulated established targets GLI1
      and SMO in human but not in mouse, suggesting species-dependent mechanism of Hh
      pathway regulation. Stable Isotope Labelling with Amino acids in Cell culture
      (SILAC), mass spectrometry and whole genome transcriptome analysis identified
      Glypican 1 (Gpc1) as a novel miR-324-5p target in mouse, which was confirmed by
      real-time RT-PCR, immunoblotting and 3'UTR-luciferase reporters. Knockdown of
      Gpc1 reduced Hh pathway activity, and phenocopied the effect of miR-324-5p on
      osteogenesis, indicating that miR-324-5p regulates Hh signalling in mouse via
      direct targeting of Gpc1. Finally, we showed that human GPC1 is not a direct
      target of miR-324-5p. Importantly, as well as identifying novel regulation of
      Indian Hedgehog (Ihh) signalling, this study demonstrates how a miRNA can show
      conserved pathway regulation in two species but by distinct mechanisms and
      highlights important differences between human diseases and mouse models.

PMID- 30193894
TI  - The laminin binding alpha3 and alpha6 integrins cooperate to promote epithelial
      cell adhesion and growth.
AB  - Integrins, the major receptors for cell-extracellular matrix (ECM) interactions,
      regulate multiple cell biological processes including adhesion, migration,
      proliferation and growth factor-dependent signaling. The principal laminin (LM)
      binding integrins alpha3beta1, alpha6beta1 and alpha6beta4 are usually co
      expressed in cells and bind to multiple laminins with different affinities making
      it difficult to define their specific function. In this study, we generated
      kidney epithelial collecting duct (CD) cells that lack both the alpha3 and alpha6
      integrin subunits. This deletion impaired cell adhesion and migration to LM-332
      and LM-511 more than deleting alpha3 or alpha6 alone. Cell adhesion mediated by
      both alpha3beta1 and alpha6 integrins was PI3K independent, but required K63
      linked polyubiquitination of Akt by the ubiquitin-modifying enzyme TRAF6.
      Moreover, we provide evidence that glial-derived neurotrophic factor (GDNF) and
      fibroblast growth factor 10 (FGF10)- mediated cell signaling, spreading and
      proliferation were severely compromised in double integrin alpha3/alpha6- but not
      single alpha3- or alpha6-null CD cells. Interestingly, these growth factor
      dependent cell functions required both PI3K- and TRAF6-dependent Akt activation.
      These data suggest that expression of the integrin alpha3 or alpha6 subunit is
      sufficient to mediate GDNF- and FGF10-dependent spreading, proliferation and
      signaling on LM-511. Thus, our study shows that alpha3 and alpha6 containing
      integrins promote distinct functions and signaling by CD cells on laminin
      substrata.

PMID- 30193895
TI  - [Serous retinal detachment secondary to choroidal osteoma].

PMID- 30193896
TI  - [Imaging of posterior corneal dystrophies].

PMID- 30193897
TI  - [Corneal neovascularization after chemical burn].

PMID- 30193898
TI  - Remotely-supervised transcranial direct current stimulation paired with cognitive
      training in Parkinson's disease: An open-label study.
AB  - BACKGROUND: Transcranial direct current stimulation (tDCS) has been explored as a
      potential intervention in Parkinson's disease (PD) and recent studies have shown
      promising results in cognitive, gait and motor function. However, evidence of
      efficacy is limited due to small size studies, short treatment periods, lack of
      standardization of methodologies and other study design limitations. Remotely
      supervised-tDCS (RS-tDCS) allows "at-home" study participation, potentially
      easing recruitment, compliance and overall feasibility for clinical studies.
      OBJECTIVE: Here, we aim to explore preliminary effects of RS-tDCS paired with
      cognitive training in PD by delivering RS-tDCS neuromodulation at participant's
      home while still maintaining clinical trial standards. METHODS: This was a
      prospective, open-label study using RS-tDCS paired with cognitive training. Each
      PD participant completed 10 tDCS sessions (20-min, 1.5-2.0-mA, bi-hemispheric
      DLPFC montage, left anodal), over a span of two weeks. All tDCS sessions were
      supervised in real-time through videoconferencing. Outcomes included the Unified
      Parkinson's Disease Rating Scale (UPDRS) and Grooved Pegboard Test. RESULTS: All
      RS-tDCS sessions were well tolerated and completed successfully. Total UPDRS and
      motor UPDRS-III scores decreased significantly. Pegboard completion time improved
      significantly for the non-dominant hand. There was a strong positive correlation
      between the time of the sessions, and motor improvements in UPDRS part-III.
      CONCLUSION: RS-tDCS paradigm through a 'telemedicine protocol' holds therapeutic
      potential for motor symptoms in PD while maximizing compliance and ease of
      recruitment. Conducting afternoon sessions might be more effective than during
      the morning. Our paradigm may be influential in designing future studies and
      facilitating larger and longer duration clinical trials.

PMID- 30193899
TI  - The use ultrasound guided for refilling intrathecal baclofene pump in complicated
      clinical cases: A practical approach.
AB  - Muscular spasticity due to neurological disorders is a heavy cause of severe pain
      and disability for many patients, compromising the independence and quality life.
      Baclofene is a good tool to guarantee patients independence and pain control.
      Anyway in chronic therapy oral treatment become unsatisfactory. In all these
      cases, intrathecal baclofen therapy (ITB), after sub fascial implantation of
      intrathecal pumps is used as an important long term treatment to reduce
      spasticity. After pump implantation the drug reservoir must be refilled
      periodically in order to maintain the reduction of spasticity and avoid the
      symptoms and signs of withdrawal. ITB refilling, which involves the insertion of
      a needle through the skin until the access port of the pump, is often hard,
      mainly due to the layer of abdominal fat, spasticity, suboptimal pump
      positioning, pump rotation or inversion, and scar formation over the implantation
      site. To avoid the difficulties of ITB refilling radiography or other invasive
      supportive examinations are sometimes needed. We reported here our experience and
      we suggest a simple method to use the ultrasound in refilling with particular
      attention to some cases with complications after implantation with a difficult
      approach in refilling. We used the ultrasound examination to identify the access
      port of her pump so as to avoid multiple needle punctures and infections and
      radiation exposition. Ultrasound-guided technique may facilitate ITB refill in
      technically challenging cases. With ultrasound ITB was easily detectable and was
      quite simple to identify the exact point of needle injection. In the last years
      different new applications for ultrasounds are emerging. In our opinion the use
      of Doppler ultrasounds in the study of muscles and nerves represent an emerging
      tool for the physician's neurological rehabilitation.

PMID- 30193900
TI  - Changes in endotracheal tube intracuff pressure and air leak pressure over time
      in anesthetized Beagle dogs.
AB  - OBJECTIVE: To evaluate endotracheal tube intracuff pressure (Pcuff) changes over
      time and the effect of these changes on air leak pressure (Pleak). STUDY DESIGN:
      Prospective experimental study. ANIMALS: A group of nine healthy adult Beagle
      dogs. METHODS: In part I, in vitro measurements of Pcuff were recorded for 1 hour
      in eight endotracheal tubes subjected to four treatments: room temperature
      without lubricant (RT0L), room temperature with lubricant (RTWL), body
      temperature without lubricant (BT0L), and body temperature with lubricant (BTWL).
      In part II, nine dogs were endotracheally intubated and Pleak was evaluated at
      Pcuff of 25 mmHg. Subsequently, Pcuff was reset to 25 mmHg (baseline) and Pcuff
      measurements were recorded every 5 minutes for 1 hour. Subsequently, a second
      Pleak measurement was recorded at the current Pcuff. The data were analyzed using
      Wilcoxon signed-rank test, repeated measures anova and Mann-Whitney U test.
      RESULTS: In part I, Pcuff differed significantly between the RT0L and RTWL
      treatments at 5-60 minutes, and between the BT0L and BTWL treatments at 5-35, 55
      and 60 minutes (p < 0.05). In part II, compared with baseline pressures, mean
      Pcuff decreased to <18 mmHg at 10 minutes and significant decreases were recorded
      at 15-60 minutes (Pcuff range: 10.0 +/- 4.9 to 13.4 +/- 6.3 mmHg, mean +/-
      standard deviation). Significant differences were observed between the first and
      second Pleak measurements (p = 0.034). Pleak decreased in six of nine dogs, was
      not changed in two dogs and increased in one dog. CONCLUSIONS AND CLINICAL
      RELEVANCE: Significant decreases in Pcuff over time were measured. Pleak may
      decrease during anesthesia and increase the risk for silent pulmonary aspiration.
      The results indicate the need for testing Pcuff more than once, especially at 10
      minutes after the onset of anesthesia.

PMID- 30193901
TI  - Comparison of NOCSAE head kinematics using the Hybrid III and EuroSID-2 necks.
AB  - Anthropomorphic test devices (ATDs) are designed for specific loading scenarios
      and possess uniquely designed individual components including the neck. The
      purpose of this study was to determine the influence of the neck surrogate on
      head kinematics. Inertial loads were generated using a pendulum system with an
      anthropomorphic head attached to a Hybrid III (HIII) or EuroSID-2 (ES-2) neck.
      The ATD head-neck assemblies were tested under extension, flexion, lateral
      bending, oblique extension, and oblique flexion at 3.4 m/s. Peak head kinematics
      were found to be statistically different with the ES-2 versus HIII neck under
      certain cases. For extension, the resultant peak linear acceleration (PLA) and
      resultant peak angular acceleration (PAA) were statistically higher with the ES-2
      versus HIII neck. For flexion and lateral bending, there were no statistical
      differences in the resultant PLA based on neck selection although the resultant
      PAA was statistically higher with the ES-2 versus HIII neck. For oblique
      extension, the resultant PLA and PAA statistically increased with the ES-2 versus
      HIII neck. Furthermore, the acceleration components ax, alphax, and alphay were
      statistically higher with the ES-2 neck while ay showed no statistical difference
      due to neck selection. For oblique flexion, the resultant PLA and PAA were
      statistically higher with the ES-2 versus HIII neck. Additionally, the
      acceleration components ax, ay, alphax, and alphay were statistically higher with
      the ES-2 versus HIII neck. These findings indicate that for certain loading
      directions and acceleration components, head kinematics were influenced by the
      neck surrogate used.

PMID- 30193902
TI  - Hyaluronic acid used as an adjunct to coronally advanced flap probably results in
      an increase in recession reduction and root coverage in patients with single
      Miller class I gingival recessions.

PMID- 30193903
TI  - Small trial suggests no differences in clinical and radiographic outcomes after
      24 months when sealing or restoring occlusal caries in primary molars.

PMID- 30193904
TI  - Utility of rapid onsite evaluation of touch imprint cytology from endoscopic and
      cholangioscopic forceps biopsy sampling (with video).
AB  - BACKGROUND AND AIMS: Rapid onsite evaluation of touch imprint cytology (ROSE-TIC)
      is a simple and rapid method used for the diagnosis of benign and malignant
      lesions. We evaluated the diagnostic accuracy of ROSE-TIC for advanced intestinal
      luminal and indeterminate pancreatobiliary lesions during endoscopy. METHODS:
      This is a retrospective descriptive study of patients who underwent endoscopy or
      ERCP between January 1, 2014 and December 31, 2016. It included patients who were
      referred for the treatment of intestinal luminal lesions or evaluation of
      indeterminate pancreatobiliary lesions. The slides were prepared by gently
      touching the specimen onto a glass slide and were examined under the microscope.
      The main outcome measure was to determine the diagnostic accuracy of ROSE-TIC by
      comparing the onsite cytology findings with the corresponding off-site histologic
      diagnosis. RESULTS: All 222 patients (106 pancreatobiliary and 116 GI lesions)
      had a prior benign diagnosis of intestinal luminal lesions or indeterminate
      diagnosis of pancreatobiliary lesions. The overall sensitivity, specificity,
      positive predictive value, negative predictive value, and diagnostic accuracy of
      ROSE-TIC were 97%, 85%, 83%, 97.2%, and 90%, respectively. The accuracy varied
      with the site of the biopsy sample. The accuracy was lowest for upper GI tract,
      where it was 85.2% but was 95% for lower GI tract lesions. CONCLUSIONS: By
      establishing a rapid onsite diagnosis, ROSE-TIC expedites decision-making on
      patient management. Prospective studies are needed to confirm these preliminary
      findings.

PMID- 30193905
TI  - Intragastric balloon outcomes in super-obesity: a 16-year city center hospital
      series.
AB  - BACKGROUND: Intragastric balloons represent an endoscopic therapy aimed at
      achieving weight loss by mechanical induction of satiety. Their exact role within
      the bariatric armamentarium remains uncertain. OBJECTIVE: Our study aimed to
      evaluate the use of intragastric balloon therapy alone and before definitive
      bariatric surgery over a 16-year period. SETTING: A large city academic bariatric
      center for super-obese patients. METHODS: Between January 2000 and February 2016,
      207 patients underwent ORBERA intragastric balloon placement at
      esophagogastroduodenoscopy. Four surgeons performed the procedures, and data were
      entered prospectively into a dedicated bariatric database. Patients' weight loss
      data were measured through body mass index (BMI) and excess weight loss and
      recorded at each clinic review for up to 5 years (60 mo). Treatment arms included
      intragastric balloon alone with lifestyle therapy or intragastric balloon and
      definitive bariatric surgery: gastric banding, sleeve gastrectomy, or Roux-en-Y
      gastric bypass. An additional treatment arm of analysis included the overall
      results from intragastric balloon followed by stapled procedure. RESULTS: One
      hundred twenty-nine female and 78 male patients had a mean age of 44.5 (+/-11.3)
      years and a mean BMI of 57.3 (+/-9.7) kg/m2. Fifty-eight percent of patients
      suffered from type 2 diabetes. Time from initial or first balloon insertion to
      definitive surgical therapy ranged between 9 and 13 months. Seventy-six patients
      had intragastric balloon alone, and 131 had intragastric balloon followed by
      definitive procedure. At 60 months postoperatively the intragastric balloon alone
      with lifestyle changes demonstrated an excess weight loss of 9.04% and BMI drop
      of 3.8; intragastric balloon with gastric banding demonstrated an excess weight
      loss of 32.9% and BMI drop of 8.9. Intragastric balloon and definitive stapled
      procedure demonstrated a BMI drop of 17.6 and an excess weight loss of 52.8%.
      Overall, there were 3 deaths (1.4%), 2 within 10 days due to acute gastric
      perforation secondary to vomiting and 1 cardiac arrest at 4 weeks
      postoperatively. CONCLUSION: Intragastric balloons can offer effective weight
      loss in selected super-obese patients within a dedicated bariatric center
      offering multidisciplinary support. Balloon insertion alone offers only short
      term weight loss; however, when combined with definitive bariatric surgical
      approaches, durable weight loss outcomes can be achieved. A strategy of early and
      continual vigilance for side effects and a low threshold for removal should be
      implemented. Surgeon and unit experience with intragastric balloons can
      contribute to "kick starting" successful weight loss as a bridge to definitive
      therapy in an established bariatric surgical pathway.

PMID- 30193906
TI  - Adipose tissue and the physiologic underpinnings of metabolic disease.
AB  - Adipose tissue dysfunction underlies the pathogenesis of metabolic disease. The
      metrics used to quantify adiposity and its association with metabolic disease,
      including body mass index, have limitations with important clinical implications.
      An understanding of the molecular and cellular mechanisms by which adipose tissue
      regulates systemic metabolism and contributes to metabolic disease will lead to
      next-generation adipose tissue-based therapy.

PMID- 30193907
TI  - Reply to Dickhoff et al. from authors of 'Induction chemoradiotherapy versus
      chemotherapy alone for superior sulcus lung cancer'.

PMID- 30193908
TI  - Microfluidic devices for disease modeling in muscle tissue.
AB  - Microfluidic devices have advanced significantly in recent years and are a
      promising technology for the field of tissue engineering. Highly sophisticated
      microfabrication techniques have paved the way for the development of complex ex
      vivo models capable of incorporating and measuring the real-time response of
      multiple cell types interacting together in a single system. Muscle-on-a-chip
      technology has drastically improved and serves as a drug screening platform for
      many muscular diseases such as muscular dystrophy, tendinosis, fibromyalgia,
      mitochondrial myopathy, and myasthenia gravis. This review seeks to communicate
      the gaps in knowledge of current muscular disease models and highlight the power
      of microfluidic devices in enabling researchers to better understand disease
      pathology and provide high throughput screening of therapeutics for muscular
      myopathies.

PMID- 30193909
TI  - Thinking outside the (pill) box: Does toxic metal exposure thwart antibiotic
      stewardship best practices?
AB  - Multi-antibiotic resistant (MAR) bacteria cost billions in medical care and tens
      of thousands of lives annually but perennial calls to limit agricultural and
      other misuse of antibiotics and to fund antibiotic discovery have not slowed this
      MAR deluge. Since mobile genetic elements (MGEs) stitch single antibiotic
      resistance genes into clinically significant MAR arrays, it is high time to focus
      on how MGEs generate MAR and how disabling them could ameliorate the MAR problem.
      However, to consider only antibiotics as the drivers of MAR is to miss the
      significant impact of exposure to non-antibiotic toxic chemicals, specifically
      metals, on the persistence and spread of MAR. Toxic metals were among the
      earliest discovered targets of plasmid-encoded resistance genes. Recent genomic
      epidemiology clearly demonstrated the co-prevalence of metal resistances and
      antibiotic multi-resistance, uniquely in humans and domestic animals. Metal
      resistances exploit the same, ancient "transportation infrastructure" of
      plasmids, transposons, and integrons that spread the antibiotic resistance genes
      and will continue to do so even if all antibiotic misuse were stopped today and
      new antibiotics were flowing from the pipeline monthly. In a key experiment with
      primates, continuous oral exposure to mercury (Hg) released from widely used
      dental amalgam fillings co-selected for MAR bacteria in the oral and fecal
      commensal microbiomes and, most importantly, when amalgams were replaced with non
      metal fillings, MAR bacteria declined dramatically. Could that also be happening
      on the larger public health scale as use of amalgam restorations is curtailed or
      banned in many countries? This commentary covers salient past and recent findings
      of key metal-antibiotic resistance associations and proposes that the shift from
      phenotyping to genotyping in surveillance of resistance loci will allow a test of
      whether declining exposure to this leading source of Hg is accompanied by a
      decline in MAR compared to countries where amalgam is still used. If this
      hypothesis is correct, the limited success of antibiotic stewardship practices
      may be because MAR is also being driven by continuous, daily exposure to Hg, a
      non-antibiotic toxicant widely used in humans.

PMID- 30193910
TI  - A new vector for heterologous gene expression in Escherichia coli with increased
      stability in the absence of antibiotic.
AB  - Expression vectors for industrial production should be stable and allow tight
      control of protein synthesis. This is necessary to ensure plasmid transmission to
      daughter cells in order to achieve a stable population capable of synthesizing
      high amounts of the target protein. A high-copy-number plasmid, pAE, was
      previously used for laboratory-scale production of recombinant human granulocyte
      colony-stimulating factor (rhG-CSF) and the Schistosoma mansoni fatty acid
      binding protein (rSm14), but it was unstable for large-scale production.
      Therefore, here we evaluated a new expression vector derived from pAE, pAR-KanI,
      which combines two plasmid replication strategies: a high-copy plasmid pUC origin
      of replication as pAE, and a par locus sequence derived from pSC101, which is
      typical of low copy plasmids, for rhG-CSF and rSm14 production in Escherichia
      coli. Clones bearing these constructs were cultivated in two complex media (2YT
      and auto-induction) and both yielded higher-than-95% resistant colonies, before
      and after induction, either with or without antibiotics. In 2YT medium, we
      obtained 244 MUg/mL of rSm14, 181 MUg/mL and 392 MUg/mL for rhG-CSF, with and
      without glucose, respectively. In auto-induction medium without antibiotics, 147
      MUg/mL of rSm14 and 162 MUg/mL of rhG-CSF were obtained. The new vector presented
      high stability for the production of both recombinant proteins in complex media
      in Escherichia coli, even in the absence of antibiotics, making the pAR-KanI a
      promising vector for industrial production of recombinant proteins.

PMID- 30193911
TI  - Hardware removal or preservation? Decision making based on a newly developed
      rating scale.
AB  - Hardware exposure following open reduction and internal fixation (ORIF) surgery
      is a tricky problem. It is always hard for surgeons to decide whether to keep or
      remove the hardware. In this study, a rating scale and corresponding clinical
      path is developed based on former published paper as well as our own experience.
      New admitted patients are first evaluated and scored once they enter the
      department. Based on the score they get, patients are assigned to different
      therapeutic schedule, i.e. (1) hardware preservation with pedicel flap
      transplantation, (2) debridement for further reevaluation and (3) hardware
      removal with external fixation. Satisfying clinical outcome is achieved that is
      characterized with high osseous consolidation rate and low complication rate. The
      result showed that this newly developed rating scale and the related therapeutic
      schedule could be an available tool to help surgeons to make decisions in the
      treatment of hardware exposure.

PMID- 30193912
TI  - Maori and Pasifika perceptions of their local maternity care in Logan, Australia.
AB  - BACKGROUND: Many childbearing women from Maori and Pasifika backgrounds living in
      the Logan region of Queensland, Australia experience poor health outcomes.
      Compared to the general population of childbearing women, Maori and Pasifika
      women are more likely to experience gestational diabetes mellitus and obesity,
      are less likely to attend recommended antenatal visits and present for initial
      antenatal visits at later gestations. AIM: To describe women's awareness of
      maternity service options, explore the barriers to participating in pregnancy
      care and identify possible enablers to improved uptake of services. METHOD:
      Qualitative descriptive. Thirty-three women attended one of six culturally
      specific focus groups. Latent content analysis was used to analyse the data set.
      FINDINGS: The key source of information for childbearing women was their
      families. Poor communication, lack of cultural safety and financial constraints
      were the major barriers to accessing services. Conversely, enablers were
      perceived to be continuity of midwifery care that was delivered in the community
      and was culturally safe. DISCUSSION: Strategies to increase uptake of maternity
      services and optimise services to better meet the needs of women from Maori and
      Pasifika backgrounds are needed. These should be partnership-based, engage women
      and families, incorporate cultural needs and preferences and provide services at
      accessible community locations. CONCLUSION: These findings may be relevant to
      other groups of women, such as women from culturally diverse backgrounds and from
      communities experiencing poorer health outcomes.

PMID- 30193913
TI  - A brief survey to identify pregnant women experiencing increased psychosocial and
      socioeconomic risk.
AB  - PROBLEM: Identifying pregnant women whose children are at risk of poorer
      development in a rapid, acceptable and feasible way. BACKGROUND: A range of
      antenatal psychosocial and socioeconomic risk factors adversely impact children's
      health, behaviour and cognition. AIM: Investigate whether a brief, waiting room
      survey of risk factors identifies women experiencing increased antenatal
      psychosocial and socioeconomic risk when asked in a private, in-home interview.
      METHODS: Brief 10-item survey (including age, social support, health, smoking,
      stress/anxious mood, education, household income, employment) collected from
      pregnant women attending 10 Australian public birthing hospitals, used to
      determine eligibility (at least 2 adverse items) for the "right@home" trial. 735
      eligible women completed a private, in-home interview (including mental health,
      wellbeing, substance use, domestic violence, housing problems). Regression models
      tested for dose-response trends between the survey risk factor count and
      interview measures. FINDINGS: 38%, 31%, 15% and 16% of women reported a survey
      count of 2, 3, 4 and 5 or more adverse risk factors, respectively. Dose-response
      relationships were evident between the survey count and interview measures, e.g.
      of women with a survey count of 2, 8% reported ever having a drug problem, 4%
      experienced domestic violence in the last year and 10% experienced housing
      problems, contrasting with 31%, 31% and 26%, respectively, for women reporting a
      survey count of 5 or more. DISCUSSION/CONCLUSIONS: A brief, waiting room survey
      of psychosocial and socioeconomic risk factors concurs with a private antenatal
      risk factor interview, and could help health professionals quickly identify which
      women would benefit from more support.

PMID- 30193914
TI  - Synthesis and characterization of cellulose nanocrystals derived from walnut
      shell agricultural residues.
AB  - Cellulose nanocrystals (CNCs) have novel and diversified applications in
      different fields including packaging and nanodelivery systems. This study was
      dedicated to fabricate CNCs from walnut shell as an abundant source of
      agricultural byproducts using alkali/acidic hydrolysis method. Moreover,
      homogenizer and ultrasound devices were applied to produce the CNCs with minimum
      hazardous solvents in the preparation steps. The physicochemical characteristics
      of CNCs, such as color, size, yield, and swelling capacity plus their
      characterization using X-ray diffraction (XRD), thermogravimetric analysis (TGA)
      and Fourier-transform infrared spectroscopy (FTIR) were studied. The mean
      equivalent spherical diameter of the fabricated CNCs was about 130 nm and the
      production efficiency was 91.5%. Besides, the swelling capacity of CNCs was 1.5
      fold of cellulose with a swelling of 400%. The crystallinity degree of the
      cellulose obtained from walnut shell was 49%, which was improved following acidic
      and alkali hydrolysis (60%). TGA analysis revealed that the thermal stability of
      the CNCs was lower than cellulose; moreover, the FTIR results demonstrated that
      there is not a considerable difference between normal cellulose and CNCs.
      Overall, it was concluded that walnut shell-derived CNCs have the potential to be
      employed as promising nanocarriers in different sectors, especially in the food
      and drug delivery sectors.

PMID- 30193915
TI  - Microstructures and properties of photophobic films composed of hydroxypropyl
      methylcellulose and different salts.
AB  - Monosodium phosphate (MP), sodium citrate (SC), sodium lactate (SL) and magnesium
      citrate (MC) can be blended with hydroxypropyl methylcellulose (HPMC) to make
      photophobic (white) films at lower drying temperatures. Small angle X-ray
      scattering (SAXS), wide angle X-ray diffraction (XRD), scanning electron
      microscopy (SEM), whiteness determination, dynamic mechanical analysis (DMA) and
      texture analysis were adopted to study the variation of microstructures and
      properties. These four kinds of HPMC/salt films showed decreased crystallinity
      and increased compactness and smoothness of the self-similar structures in larger
      scale ranges. HPMC/MP, HPMC/SC and HPMC/SL film showed coarser and porous
      morphologies, lower mechanical parameters and higher whiteness than pure HPMC
      film. HPMC/MC film showed smoother morphologies, higher tensile strength,
      elongation and whiteness than pure HPMC film. Porous structures and more compact
      self-similar structures might contribute to the photophobic property of these
      films, and relatively smooth morphology might dominate the increasing mechanical
      parameters of HPMC/MC film.

PMID- 30193916
TI  - Cholinesterases inhibition studies of biological active compounds from the
      rhizomes of Alpinia officinarum Hance and in silico molecular dynamics.
AB  - Six diarylheptanoids (1-6) and two flavonoids (7 and 8) derived from Alpinia
      officinarum were evaluated for their ability to inhibit acetylcholinesterase.
      Compound 1 showed the highest degree of inhibition, with an IC50 of approximately
      2 MUM, followed by moderate degrees of inhibition by 2, 4 and 7, with IC50 values
      ranging from 20 to 40 MUM. The remaining isolated compounds 3, 5, 6 and 8 had
      IC50 values greater than 50 MUM. Enzyme kinetic studies showed that the compounds
      with high or moderate activity were competitive inhibitors, anchored to the
      active site of acetylcholinesterase. In particular, compounds 1 and 2 were docked
      at slightly different positions from those occupied by 4 and 7. Furthermore,
      molecular dynamics studies showed that compound 1 maintained its interactions
      with residues Thr74 and Phe295 throughout the simulation trajectory. Our findings
      suggest that compound 1 is a potential therapeutically relevant inhibitor of
      acetylcholinesterase.

PMID- 30193917
TI  - Selective reduction in glutaminase activity of l-Asparaginase by asparagine 248
      to serine mutation: A combined computational and experimental effort in blood
      cancer treatment.
AB  - Type II l-asparaginase (l-ASNase) is an FDA approved enzyme drug with extensive
      applications for treatment of certain blood cancers. However, the therapeutic
      efficiency of this enzyme is hampered by its undesirable glutaminase activity.
      Given the pivotal role of this enzyme against cancer, designing engineered
      mutants with diminished glutaminase activity would be of great therapeutic
      interest. To this end, N248S mutation was selected as the potential mutation with
      beneficial effects. Various in silico analyses including MD simulation, molecular
      docking and QMMM studies were performed to assess the effects of N248S mutation
      on the activity of the enzyme. Thereafter, this mutation along with N248A, N248V
      and N248T mutations as controls were exerted in l-ASNase gene. The results from
      in silico analyses and experimental efforts indicated that N248S mutation is
      associated with the suitable l-ASNase activity, while the glutaminase activity is
      disturbed due to impaired interactions. It has been shown that glutamine turnover
      was affected much more strongly than asparagine hydrolysis. The approach of
      exploiting in silico tools to design mutated enzymes lead to staggering time and
      cost reduction. Following this strategy, we have designed a mutant l-ASNase with
      diminished glutaminase activity, which could be of interest for improved
      biomedical applications.

PMID- 30193918
TI  - How the Triton X-100 modulates the activity/stability of the Thermomyces
      lanuginose lipase: Insights from experimental and molecular docking approaches.
AB  - The lipase and Triton X-100 mixture is common for stabilization, immobilization
      and application processes of these kinds of enzymes. The objective of this
      article was to study the structural behavior and catalytic performance of
      Thermomyces lanuginose lipase in the presence of Triton X-100 at 25  degrees C
      and different pHs. The structural changes were followed by circular dichroism,
      correlating them with the catalytic performance, which is reported as the initial
      lipase activity in the hydrolysis of p-nitro phenyl butyrate at zero time and
      residual activity after 48 h of incubation in the absence or presence of
      surfactant, at the selected pHs. Computational simulations allowed to explain the
      correlations between the physicochemical changes and the formation of surfactant
      protein complex, leading to the elucidation of the main interactions that drive
      activity and stability of this lipase in presence of the Triton X-100 surfactant.
      Main results showed the Triton X-100-enzyme complex modulates the site active
      geometry, favoring a better substrate-enzyme adjustment, which influences the
      activity and stability at evaluated pHs. This study contributes to understand the
      effect of some additives commonly used to improve the biocatalytic performance on
      several applications for different industrial fields.

PMID- 30193919
TI  - Guar gum mediated synthesis of NiO nanoparticles: An efficient catalyst for
      reduction of nitroarenes with sodium borohydride.
AB  - An excellent catalyst (GNiOc) for reduction of nitroarenes with sodium
      borohydride is being reported. The synthesis of GNiOc was carried out by direct
      precipitation method using guar gum (GG) as the modifier. The nanostructures have
      been characterized using UV-visible spectroscopy (UV-vis), Fourier transformation
      infrared spectroscopy (FTIR), Brunauer-Emmett-Teller (BET) surface area analysis,
      X-ray diffraction (XRD), Scanning electron microscopy (SEM), Transmission
      electron microscopy (TEM), and Thermal (TGA and DTA) analysis. TEM analysis
      revealed that GNiOc sample is crystalline in nature (similar to cubic NiO) and
      had an average particle size of ~3 nm. The reduction of 4-nitrophenol (4-NP) (2
      mM) using sodium borohydride (0.1 M) was completed within 2 min when GNiOc (5 mg)
      was used as catalyst. GNiOc could be successfully recovered and reused for six
      repetitive cycles and even in the sixth cycle; the reduction was completed in 18
      min time. The reduction followed zero order kinetics, the rate constant being 8 *
      10-3 mmol L-1 min.-1 Under identical experimental conditions, GNiOc catalyzed
      reductions (with sodium borohydride) of 4-nitroaniline (4-NA) and 4-nitro benzoic
      acid (4-NBA) were completed in 6 and 7 min respectively, while NiO required >15
      min time for reducing all the three nitroarenes.

PMID- 30193920
TI  - Comparative proteomics analysis of whitetop (Lepidium draba L.) seedlings in
      response to exogenous glucose.
AB  - In this research, a comparative proteomics approach was conducted to understand
      the physiological processes behind the sulforaphane formation in whitetop
      seedlings in response to exogenous glucose. Initially, 5-day-old whitetop
      seedlings were elicited by different concentrations (0, 166, 250, 277, 360 mM) of
      glucose for 72 h. According to the results, sulforaphane formation was influenced
      in a dose-dependent manner by glucose, and was maximized with the concentrations
      of 166 and 250 mM. Consequently, 2-dimensional gel electrophoresis was performed
      on the 166 mM glucose-elicited seedlings and it was shown that 25 protein spots
      were differentially expressed between glucose-elicited seedlings and control. Two
      hypothetical (were down-regulated) and 9 unique proteins (44% and 56% up- and
      down-regulated, respectively) were identified based on the Mass spectrometry
      analysis. According to the functional classification of the unique proteins,
      photosynthetic, chaperone, energy metabolism, signaling and sorting related
      proteins are marked in response to the glucose elicitation. This is the first
      report to successfully identify the Abscisic acid receptor PYR1-like and sorting
      nexin 1 isoform X1 by proteomics technique. In addition, the role of the sorting
      nexin 1 isoform X1 in the glucose-elicited whitetop seedling is reported for the
      first time.

PMID- 30193921
TI  - Virtual screening and drug repositioning as strategies for the discovery of new
      antifungal inhibitors of oxidosqualene cyclase.
AB  - Candidiasis is the most common fungal infection in immunocompromised patients,
      and Candida albicans is the fourth leading agent of nosocomial infections.
      Mortality from this infection is significant; however, the therapeutic treatment
      is limited, which demands the search for new drugs and new targets. In this
      context, oxidosqualene cyclase (OSC) catalyzes the cyclization of the 2,3
      oxidosqualene to form lanosterol, an intermediate of ergosterol biosynthesis.
      Therefore, this enzyme constitutes an attractive therapeutic target. Thus, the
      aim of this study is to identify potential inhibitors of C. albicans OSC (CaOSC)
      from a marketed drugs database in order to discover new antifungal agents. The
      CaOSC 3D model was constructed using the Swiss-Model server and important
      features for CaOSC inhibition were identified by molecular docking of known
      inhibitors using Autodock Vina 1.1.2. Subsequently, virtual screening helped to
      identify calcitriol, the active form of vitamin D, and other four drugs, as
      potential inhibitors of CaOSC. The selected drugs presented an interesting
      pattern of interactions with this enzyme, including hydrogen bond with Asp450, a
      key residue in the active site. Thus, the antifungal activity of calcitriol was
      evaluated in vitro against Candida spp strains. Calcitriol showed antifungal
      activity against C. albicans and C. tropicalis, which reinforces the potential of
      this compound as candidate of CaOSC inhibitor. In short, the present study
      provides important insights for the development of new oxidosqualene cyclase
      inhibitors as antifungals.

PMID- 30193922
TI  - Dietary exacerbation of metabolic stress leads to accelerated hepatic
      carcinogenesis in glycogen storage disease type Ia.
AB  - BACKGROUND & AIMS: Glycogen storage disease type Ia (GSDIa) is a rare genetic
      disease associated with glycogen accumulation in hepatocytes and steatosis. With
      age, most adult patients with GSDIa develop hepatocellular adenomas (HCA), which
      can progress to hepatocellular carcinomas (HCC). In this study, we characterized
      metabolic reprogramming and cellular defense alterations during tumorigenesis in
      the liver of hepatocyte-specific G6pc deficient (L.G6pc-/-) mice, which develop
      all the hepatic hallmarks of GSDIa. METHODS: Liver metabolism and cellular
      defenses were assessed at pretumoral (four months) and tumoral (nine months)
      stages in L.G6pc-/- mice fed a high fat/high sucrose (HF/HS) diet. RESULTS: In
      response to HF/HS diet, hepatocarcinogenesis was highly accelerated since 85% of
      L.G6pc-/- mice developed multiple hepatic tumors after nine months, with 70%
      classified as HCA and 30% as HCC. Tumor development was associated with high
      expression of malignancy markers of HCC, i.e. alpha-fetoprotein, glypican 3 and
      beta-catenin. In addition, L.G6pc-/- livers exhibited loss of tumor suppressors.
      Interestingly, L.G6pc-/- steatosis exhibited a low-inflammatory state and was
      less pronounced than in wild-type livers. This was associated with an absence of
      epithelial-mesenchymal transition and fibrosis, while HCA/HCC showed a partial
      epithelial-mesenchymal transition in the absence of TGF-beta1 increase. In
      HCA/HCC, glycolysis was characterized by a marked expression of PK-M2, decreased
      mitochondrial OXPHOS and a decrease of pyruvate entry in the mitochondria,
      confirming a "Warburg-like" phenotype. These metabolic alterations led to a
      decrease in antioxidant defenses and autophagy and chronic endoplasmic reticulum
      stress in L.G6pc-/- livers and tumors. Interestingly, autophagy was reactivated
      in HCA/HCC. CONCLUSION: The metabolic remodeling in L.G6pc-/- liver generates a
      preneoplastic status and leads to a loss of cellular defenses and tumor
      suppressors that facilitates tumor development in GSDI. LAY SUMMARY: Glycogen
      storage disease type Ia (GSD1a) is a rare metabolic disease characterized by
      hypoglycemia, steatosis, excessive glycogen accumulation and tumor development in
      the liver. In this study, we have observed that GSDIa livers reprogram their
      metabolism in a similar way to cancer cells, which facilitates tumor formation
      and progression, in the absence of hepatic fibrosis. Moreover, hepatic burden due
      to overload of glycogen and lipids in the cells leads to a decrease in cellular
      defenses, such as autophagy, which could further promote tumorigenesis in the
      case of GSDI.

PMID- 30193923
TI  - Reply to: "Non-invasive prediction of oesophageal varices in patients with
      cirrhosis secondary to non-alcoholic fatty liver disease".

PMID- 30193924
TI  - Rapid antimicrobial susceptibility testing by matrix-assisted laser desorption
      ionization-time of flight mass spectrometry using a qualitative method in
      Acinetobacter baumannii complex.
AB  - The transmission and infections of multidrug-resistant bacteria can be prevented
      by rapid identification and antibiotic susceptibility testing (AST) for
      pathogenic bacteria in a clinical microbiology laboratory. Matrix-assisted laser
      desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has been
      routinely used as a tool for the identification of pathogens; however, a simple
      and accurate method for a rapid determination of the antimicrobial susceptibility
      profile is an urgent requisite. The present study established a method based on
      mass spectrometry to determine the drug resistance. Acinetobacter baumannii
      complex isolates were tested as an example. After short-term culture, the
      isolates were incubated with meropenem of different concentrations to determine
      the growth or the inhibition of the growth by MALDI-TOF MS. The agreement of
      minimum inhibitory concentration (MIC) values between MALDI-TOF MS-based rapid
      AST and broth microdilution method in susceptible and resistant strains was 77.1%
      and 70.1%, respectively. The susceptibility-breakpoint concentration (2 MUg/mL)
      achieved a 98.9% sensitivity and 100% specificity with respect to resistance
      detection. Similarly, 96.9% sensitivity and 100% specificity were obtained for
      resistance detection with meropenem concentration at 8 MUg/mL. MALDI-TOF MS-based
      rapid AST was applied to determine the drug resistance at breakpoint
      concentration, although MS-MICs might shift to a low dilution. Thus, it is
      critical for patients to accelerate the AST result from two days to several
      hours.

PMID- 30193925
TI  - [Blood transfusion in neonatology: Study of practical aspects in 2016 in France,
      excluding acute bleeding or surgical care].
AB  - BACKGROUND: Blood transfusion is common in neonatology, especially in preterm or
      low birth weight infants. Recommendations were proposed by the French National
      Authority of Health (HAS) in 2014 and 2015 for red blood cells and platelet
      transfusion respectively, but an heterogeneity of practical attitudes persist.
      The objective of this survey is to evaluate transfusion practices in neonatal
      intensive care units. METHODS: Investigation of practice of neonatal transfusion
      was organized among 68 neonatal intensive care unit (level 3) between September
      2016 and May 2017, by mailing survey focused on systematic training of nurses,
      patient identification, immunohematology, information and technical aspects of
      blood components administration. RESULTS: Twenty-three neonatal intensive care
      units among the 68s answered the questionnaire. One thousand five hundred sixty
      seven neonates were transfused and 3382 blood products were administered. The
      results highlight a consensual attitude concerning the procedures of patient
      identification, immunohematology tests and blood products administration.
      However, heterogeneity remains concerning information of the parents or the
      person with parental authority, immediate and delayed follow-up and devices used
      for the transfusion. However HAS guidelines (2014 and 2015) appear to be well
      applied by clinicians for blood products, specifications and calcul of transfused
      volume based on gestational age and weight.

PMID- 30193926
TI  - Intra-articular effects of combined xenogenous serum rich in growth factors
      (SRGF) and vitamin C on histopathology grading and staging of osteoarthritis in
      rat model.
AB  - OBJECTIVE: Osteoarthritis (OA) is one of the most common degenerative diseases
      especially in the knee joint. The definitive method for the treatment of this
      disease is not known. In recent years, use of platelet-derived products has been
      considered as a new therapeutic approach because of its low cost, easy to use,
      and minimum side effects. Serum rich of growth factors (SRGF) is one of the
      biological compounds used to healing and regeneration. Its effects may improve in
      combination with antioxidants such as vitamin C. This vitamin increases the
      synthesis of proteoglycans by chondrocytes. The present study investigated effect
      of xenogenous SRGF in combination with vitamin C on the monosodium iodoacetate
      induction osteoarthritis in rats. METHODS: Animals were randomly categorized into
      three groups including OA, SRGF, and vitamin C+SRGF. Treatments were performed
      with 3 time intra-articular injection in weekly intervals. Knee samples were
      taken after two weeks of the last treatment for histopathologic investigations.
      RESULTS: In the OA group, surface fibrillation and irregularity, multiple clefts,
      loss of chondrocytes, proteoglycan depletion with Toluidine blue staining were
      detected. In the treated group with SRGF/vitamin C, the severity of degenerative
      lesions was decreased. Chondrocytes had proliferated and matrix proteoglycan
      increased in compared to the SRGF and OA groups. Also, osteoarthritis stage was
      markedly reduced in this group rather than two other groups. CONCLUSION: The
      results of this study show the synergic effect of vitamin C and growth factors on
      accelerating articular repair.

PMID- 30193927
TI  - Submicron loteprednol etabonate ophthalmic gel 0.38% for the treatment of
      inflammation and pain after cataract surgery.
AB  - PURPOSE: To assess the safety and efficacy of a 0.38% submicron formulation of
      loteprednol etabonate (LE) gel for the treatment of postoperative inflammation
      and pain after cataract surgery. SETTING: Forty-five United States ophthalmology
      practices. DESIGN: Double-masked vehicle-controlled randomized parallel group
      study. METHODS: Patients 18 years of age or older with anterior chamber cells
      grade 2 or higher on day 1 after uncomplicated cataract surgery were randomized
      to 14 days of treatment with LE gel 2 times a day, LE gel 3 times a day, or
      vehicle. Hierarchical primary endpoints were the proportion of patients with
      resolution of anterior chamber cells and grade 0 (no) pain at postoperative day
      8. Safety outcomes included adverse events, intraocular pressure (IOP),
      biomicroscopy, visual acuity, ophthalmoscopy, and tolerability (drop comfort and
      ocular symptoms). RESULTS: The intent-to-treat population included 514 patients.
      Significantly more patients in the LE gel 2 times a day and 3 times a day groups
      compared with the vehicle group had complete resolution of anterior chamber cells
      (26.9% and 28.7% versus 9.3%) and reported grade 0 pain (73.7% and 73.1% versus
      47.7%) on day 8 (P < .001 vs vehicle for all). The safety findings were
      unremarkable, with 1 patient experiencing an IOP increase of 10 mm Hg or higher
      while on LE gel. More than 75% of patients in each group reported no drop
      discomfort. CONCLUSION: In this study, submicron loteprednol etabonate gel 0.38%
      appeared safe and effective in the treatment of postoperative inflammation and
      pain whether instilled 2 times or 3 times a day.

PMID- 30193928
TI  - Novel peptide-dendrimer/lipid/oligonucleotide ternary complexes for efficient
      cellular uptake and improved splice-switching activity.
AB  - Despite the advances in gene therapy and in oligonucleotide (ON) chemistry,
      efficient cellular delivery remains an obstacle. Most current transfection
      reagents suffer from low efficacy or high cytotoxicity. In this report, we
      describe the synergism between lipid and dendrimer delivery vectors to enhance
      the transfection efficiency, while avoiding high toxicity. We screened a library
      of 20 peptide dendrimers representing three different generations and evaluated
      their capability to deliver a single-stranded splice-switching ON after
      formulating with lipids (DOTMA/DOPE). The transfection efficiency was analyzed in
      5 reporter cell lines, in serum-free and serum conditions, and with 5 different
      formulation protocols. All formulations displayed low cytotoxicity to the
      majority of the tested cell lines. The complex sizes were < 200 nm; particle size
      distributions of effective mixtures were < 80 nm; and, the zeta potential was
      dependent on the formulation buffer used. The best dendrimer enhanced
      transfection in a HeLa reporter cell line by 30-fold compared to untreated cells
      under serum-free conditions. Interestingly, addition of sucrose to the
      formulation enabled - for the first time - peptide dendrimers/lipid complexes to
      efficiently deliver splice-switching ON in the presence of serum, reaching 40
      fold increase in splice switching. Finally, in vivo studies highlighted the
      potential of these formulae to change the biodistribution pattern to be more
      towards the liver (90% of injected dose) compared to the kidneys (5% of injected
      dose) or to unformulated ON. This success encourages further development of
      peptide dendrimer complexes active in serum and future investigation of
      mechanisms behind the influence of additives on transfection efficacy.

PMID- 30193929
TI  - A cautionary note on the use of cap analogue affinity resins.
AB  - All cellular cytoplasmic mRNAs are capped at their 5' ends with an m7GpppN group.
      Several proteins that mediate cap function have been identified by cap affinity
      purification, enabling their characterization in a number of biological
      processes. Among these, eukaryotic initiation factor (eIF) 4E is the best
      characterized and plays a critical role in regulating ribosome recruitment to
      mRNAs during translation initiation. Cap affinity chromatography is often used to
      identify eIF4E-interacting proteins, which could play critical roles in molding
      the eIF4E-interactome and impacting on eIF4E-directed translation. Here we
      address how improper implementation of this technology can lead to false
      conclusions and provide recommendations to ensure correct interpretation of data
      obtained by this approach.

PMID- 30193930
TI  - Enrichment of midsized RNAs with manganese chloride precipitation.
AB  - Enrichment of specific RNAs is important for RNA analysis. MnCl2 has been used
      previously to enrich viroid RNA fractions from total RNA from infected plants. We
      have expanded this method to show that MnCl2 can enrich single-stranded as well
      as structured RNAs of 450 nt and below from a total RNA preparation. We have
      applied this method to map the transcription start sites of a PSTVd transcript
      from total RNA from yeast under conditions where the RNA was previously
      undetectable.

PMID- 30193931
TI  - Role of Apparent Temperature and Air Pollutants in Hospital Admissions for Acute
      Myocardial Infarction in the North of Spain.
AB  - INTRODUCTION AND OBJECTIVES: The role of the environment on cardiovascular health
      is becoming more prominent in the context of global change. The aim of this study
      was to analyze the relationship between apparent temperature (AT) and air
      pollutants and acute myocardial infarction (AMI) and to study the temporal
      pattern of this disease and its associated mortality. METHODS: We performed a
      time-series study of admissions for AMI in Cantabria between 2001 and 2015. The
      association between environmental variables (including a biometeorological index,
      AT) and AMI was analyzed using a quasi-Poisson regression model. To assess
      potential delayed and non-linear effects of these variables on AMI, a lag non
      linear model was fitted in a generalized additive model. RESULTS: The incidence
      rate and the mortality followed a downward trend during the study period (CC=
      0.714; P=.0002). An annual pattern was found in hospital admissions (P=.005),
      with the highest values being registered in winter; a weekly trend was also
      identified, reaching a minimum during the weekends (P=.000005). There was an
      inverse association between AT and the number of hospital admissions due to AMI
      and a direct association with particulate matter with a diameter smaller than 10
      MUm. CONCLUSIONS: Hospital admissions for AMI followed a downward trend between
      2007 and 2015. Mortality associated with admissions due to this diagnosis has
      decreased. Predictive factors for this disease were AT and particulate matter
      with a diameter smaller than 10 MUm.

PMID- 30193932
TI  - Comparative evaluation of 2 automated molecular systems for the detection of HSV
      1 and 2 from genital swab specimens.
AB  - BD ProbeTec HSV 1 & 2 Qx (on the BD Viper XTR) and the Aptima HSV 1 & 2 (on the
      Hologic Panther) assays were compared. Of 257 clinical samples, 96.6% positive
      and 88.5% negative results were concordant, respectively. The BD assay was more
      sensitive than the Aptima, but the latter was more specific.

PMID- 30193933
TI  - Effects of gem-dihydroperoxides against mutant copper-zinc superoxide dismutase
      mediated neurotoxicity.
AB  - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized
      by progressive muscle weakness, paralysis, and death. Although its neuropathology
      is well investigated, currently, effective treatments are unavailable. The
      mechanism of ALS involves the aggregation and accumulation of several mutant
      proteins, including mutant copper-zinc superoxide dismutase (SOD1), TAR DNA
      binding protein 43 kDa (TDP-43) and fused in sarcoma (FUS) proteins. Previous
      reports have shown that excessive oxidative stress, associated with mitochondrial
      dysfunction and mutant protein accumulation, contributes to ALS pathology. The
      present study focuses on the promotion of SOD1 misfolding and aggregation by
      oxidative stress. Having recently synthesized novel organic gem-dihydroperoxides
      (DHPs) with high anti-oxidant activity, we now examined whether DHPs reduce the
      mutant SOD1-induced intracellular aggregates involved in oxidative stress. We
      found that, among DHPs, 12AC2O significantly inhibited mutant SOD1-induced cell
      death and reduced the intracellular mutant SOD1 aggregates. Moreover,
      immunofluorescence staining with redox-sensitive dyes showed that 12AC2O reduced
      the excessive level of intracellular mutant SOD1-induced reactive oxygen species
      (ROS). Additionally, ESR analysis showed that 12AC2O exerts a direct scavenging
      effect against the hydroxyl radical (OH) and the superoxide anion (O2-). These
      results suggest that 12AC2O is a very useful agent in combination with other
      agents against ALS.

PMID- 30193934
TI  - Effects of Yellow Sea Cold Water Mass on marine nematodes based on biological
      trait analysis.
AB  - The Yellow Sea Cold Water Mass (YSCWM) is a seasonal hydrological phenomenon with
      significant effects on benthic animals. Based on a range of biological traits,
      including feeding type, tail shape, adult body length, body shape and life
      history (c-p value), the biological trait analysis (BTA) of marine nematodes in
      the southern Yellow Sea was studied in June 2003 (summer) and January 2004
      (winter) in order to reveal the effects of YSCWM on benthic animals. In terms of
      biological traits composition of marine nematode assemblages, results of ANOSIM
      showed that there were no significant differences among sites inside the YSCMW
      area. However, for spatial distribution, marine nematode assemblages showed
      significant differences between sites inside and outside of the YSCWM area in
      terms of body shape, as there was higher percentage of nematodes with slender
      body shape while lower percentage with stout and long thin body shape at the
      sites inside the YSCWM area. Results of BIOENV analysis showed that water depth
      and sediment silt-clay percentage were the most important factors contributed to
      the differences of biological traits of marine nematode assemblages in summer,
      while sediment phaeophorbide content best explained the differences of marine
      nematode assemblages in winter. The existence of the YSCWM may provide a stable
      environment for marine nematode assemblages, keeping them in a continuous state
      during the seasonal changes. The higher percentage of nematodes with slender body
      may be the response to the YSCWM.

PMID- 30193935
TI  - Children with Neutrophil-Predominant Severe Asthma Have Proinflammatory
      Neutrophils With Enhanced Survival and Impaired Clearance.
AB  - BACKGROUND: Airway neutrophils are abundant in some children with severe asthma,
      but their functions are poorly understood. OBJECTIVE: To characterize that the
      inflammatory airway environment of children with neutrophil-predominant severe
      asthma promotes neutrophil survival and disrupts neutrophil-associated innate
      immune defenses. METHODS: Sixty-seven children with severe asthma refractory to
      high-dose inhaled corticosteroid treatment undergoing bronchoscopy with
      bronchoalveolar lavage (BAL) for clinical indications were stratified into
      neutrophil "high" versus "low" groups on the basis of BAL differential counts.
      Neutrophil activation markers, functional assays, and phenotyping studies were
      performed, as well as airway macrophage functional assays. Results were compared
      with those from children with moderate asthma treated with inhaled
      corticosteroids. RESULTS: Children with neutrophil-predominant severe asthma had
      increased markers of neutrophil activation/degranulation and a greater magnitude
      of airway proinflammatory cytokine and chemokine release. Primary neutrophils
      exposed to BAL of these children exhibited greater phagocytic capability and
      greater neutrophil extracellular trap formation, but a more impaired respiratory
      burst. Despite greater abundance of airway TGF-beta1, the neutrophils were not
      more apoptotic. Instead, neutrophils had a highly proinflammatory phenotype
      associated with a number of surface markers that regulate neutrophil activation,
      recruitment/migration, and granule release. Airway macrophages from children with
      neutrophil-predominant severe asthma were also more proinflammatory with impaired
      phagocytosis and increased apoptosis. CONCLUSIONS: Children with neutrophil
      predominant severe asthma have proinflammatory neutrophils with enhanced
      survival. Airway macrophages are also proinflammatory and dysfunctional and may
      contribute to global innate immune impairment. Therapies that target neutrophils
      and related inflammation may be warranted in this subset of children.

PMID- 30193936
TI  - Effects of Reslizumab on Asthma Outcomes in a Subgroup of Eosinophilic Asthma
      Patients with Self-Reported Chronic Rhinosinusitis with Nasal Polyps.
AB  - BACKGROUND: An estimated 7% of patients with asthma have chronic rhinosinusitis
      with nasal polyps (CRSwNP), and more than 80% have at least some radiographic
      evidence of sinonasal inflammation. Aspirin sensitivity is strongly associated
      with elevated blood eosinophil levels and increased asthma severity. Intravenous
      (IV) reslizumab has been shown to improve asthma control in patients with nasal
      polyps. OBJECTIVE: These post hoc analyses of pooled data from 2 BREATH phase 3
      clinical trials, studies 1 and 2 (NCT01287039 and NCT01285323), examined asthma
      related outcomes in patients with comorbid, self-reported CRSwNP with and without
      aspirin sensitivity. METHODS: Patients aged 12-75 years with elevated blood
      eosinophils (>=400 cells/MUL) and inadequately controlled asthma were randomized
      to receive placebo or reslizumab (3 mg/kg IV) every 4 weeks for 52 weeks.
      Patients continued their background asthma maintenance therapy during the study.
      Information regarding the presence of CRSwNP was obtained through patient
      reported medical history. RESULTS: Add-on reslizumab treatment reduced the
      frequency of clinical asthma exacerbations by 83% versus placebo among patients
      with CRSwNP. Among patients with and without aspirin sensitivity, reductions of
      79% and 84%, respectively, were observed. Patients with CRSwNP (with and without
      aspirin sensitivity) treated with reslizumab add-on therapy also had significant
      improvements in lung function, as measured by forced expiratory volume in 1
      second, compared with placebo. Among patients with CRSwNP, reslizumab was also
      associated with improvements in patient-reported asthma control and asthma
      quality of life. CONCLUSIONS: Patients with eosinophilic asthma and self-reported
      CRSwNP, with and without aspirin sensitivity, are highly responsive to treatment
      with reslizumab for asthma-related outcomes. These findings suggest that
      prospective investigation of reslizumab in this patient population is warranted.

PMID- 30193937
TI  - Staphylococcus aureus Nasal Colonization and Asthma in Adults: Systematic Review
      and Meta-Analysis.
AB  - BACKGROUND: Staphylococcus aureus (SA) is a frequent colonizer in humans, and it
      is known to be associated with chronic allergic diseases including asthma. Recent
      individual studies suggested that nasal SA colonization may be positively
      associated with asthma. OBJECTIVE: To examine relationships between nasal SA
      colonization and asthma prevalence and activity in adults. METHODS: Electronic
      databases were searched for studies published until June 2018. Studies that
      reported nasal SA colonization prevalence and asthma outcome (prevalence and
      disease activity) in general adult populations or patients with chronic
      rhinosinusitis (CRS) were included. Random effects meta-analyses were performed
      to calculate pooled odds ratio (OR) of the relationships. Subgroup analysis was
      conducted for the presence of nasal polyps within CRS populations. RESULTS: A
      total of 21 cross-sectional studies were identified, and the data from 16 studies
      using culture methods for SA detection were meta-analyzed (5 general population
      based studies and 11 studies of patients with CRS). In studies of general
      populations, nasal SA colonization had significant relationships with asthma
      prevalence (OR 1.19; 95% confidence interval [CI] 1.06-1.34; I2 = 1%). In studies
      of patients with CRS, positive associations were also found but had a
      considerable heterogeneity (OR 1.87; 95% CI 1.18-2.97; I2 = 72%). However, the
      results were comparable between CRS with and without nasal polyps. CONCLUSIONS:
      This study demonstrated modest but significant relationships between nasal SA
      colonization and asthma, supporting potential roles of SA in adult patients with
      asthma. Further longitudinal cohort and intervention studies are warranted to
      identify host determinants and to clarify causality of the relationships.

PMID- 30193938
TI  - Patient versus allergy specialist interpretation of a negative workup for
      suspected iodinated contrast media allergy.

PMID- 30193939
TI  - Bronchial Thermoplasty: A Decade of Experience: State of the Art.
AB  - Bronchial thermoplasty (BT) delivers targeted radiofrequency energy to bronchial
      airway walls and results in the partial ablation of the airway smooth muscle that
      is responsible for bronchoconstriction. It is approved for the treatment of
      severe persistent asthma. Multiple, large clinical trials including a recent
      "real-world" study demonstrate significant improvements in asthma-related quality
      of life, reduction in asthma exacerbations, emergency department visits, and
      hospitalizations after BT that is sustained out to 5 years. In this article, we
      review the state of the art of BT treatment in severe persistent asthma and share
      a decade of BT research and clinical experience. We share our personal experience
      and introduce the three "I"s (identification, implementation, and intense follow
      up) that we believe promote successful patient outcomes and help build a
      successful BT program.

PMID- 30193940
TI  - Fatal Asthma: An Audit of 30 Million Patient-Years of Health Plan Membership from
      2007 to 2015.
AB  - BACKGROUND: Without accurate data on deaths directly caused by asthma, prevention
      will be difficult. OBJECTIVE: To determine how often asthma could be confirmed as
      a proximal cause of death in a large well-defined population with active health
      plan membership and no acute barriers to medical care. METHODS: All deaths
      occurring in active Kaiser Permanente Southern California health plan members
      between 2007 and 2015 were identified. Asthma-coded deaths were manually audited
      for cause. Health care and asthma medication use in the 6 months before death
      were determined. RESULTS: There were 248 (0.80 per 100,000 patient-years)
      unaudited asthma-coded deaths. There were only 63 (26.5%) (0.20 per 100,000
      patient-years) asthma-confirmed deaths. Individuals with asthma-confirmed deaths
      were younger, less likely to have ever smoked, and had fewer emergency visits in
      the 6 months before death compared with those with asthma excluded. Individuals
      with asthma-confirmed deaths used preventative inhalers at very low rates. We
      unexpectedly found that ever inclusion in the 2016 National Committee for Quality
      Assurance health effectiveness data and information set (HEDIS) for persistent
      asthma was associated with a higher risk of all-cause early death. Individuals
      with asthma-confirmed deaths were also unlikely to be in the HEDIS asthma dataset
      in the year they died, thus not targeted for outreach. CONCLUSIONS: Audit
      confirmed fatal asthma is more likely to occur in younger, nonsmoking,
      individuals, using very low rates of preventive inhalers. This will be a very
      difficult group to prospectively identify and manage effectively. Further
      research into the reasons for early death after HEDIS asthma dataset inclusion is
      warranted.

PMID- 30193941
TI  - In vitro and in vivo anti-inflammatory properties of imine resveratrol analogues.
AB  - Resveratrol is a natural polyphenol found mainly on red grapes and in red wine,
      pointed as an important anti-inflammatory/immunomodulatory molecule. However, its
      bioavailability problems have limited its use encouraging the search for new
      alternatives agents. Thus, in this study, we synthetize 12 resveratrol analogues
      (6 imines, 1 thioimine and 5 hydrazones) and investigated its cytotoxicity,
      antioxidant activity and in vitro anti-inflammatory/immunomodulatory properties.
      The most promising compounds were also evaluated in vivo. The results showed that
      imines presented less cytotoxicity, were more effective than resveratrol on DPPH
      scavenger and exhibited an anti-inflammatory profile. Among them, the imines with
      a radical in the para position, on the ring B, not engaged in an intramolecular
      hydrogen-interaction, showed more prominent anti-inflammatory activity
      modulating, in vivo, the edema formation, the inflammatory infiltration and
      cytokine levels. An immunomodulatory activity also was observed in these
      molecules. Thus, our results suggest that imines with these characteristics
      presents potential to control inflammatory disorders.

PMID- 30193942
TI  - Modulation of bovine herpesvirus 1 infection by virally encoded microRNAs.
AB  - Bovine herpesvirus 1 (BoHV-1), is a member of the subfamily Alphaherpesvirinae in
      the order Herpesviridae and is a ubiquitous pathogen of cattle responsible for
      significant economic loss worldwide. The BoHV-1 genome encodes at least 10 BoHV-1
      microRNA (miRNA) genes, whose functions remain poorly understood. This study
      sought to understand the role of three BoHV-1 miRNA genes, Bhv1-miR-B6, Bhv1-miR
      B8 and Bhv1-miR-B9, which are located proximal to the BoHV-1 origins of
      replication (OriS). Therefore, plasmids expressing the precursor miRNA hairpins
      for the Bhv1-miR-B6, Bhv1-miR-B8, and Bhv1-miR-B9 genes were constructed and
      transfected into Madin-Darby bovine kidney cells prior to BoHV-1 infection.
      Interestingly, transient expression of either Bhv1-miR-B8 or Bhv1-miR-B9 in Madin
      Darby bovine kidney cells prior to infection resulted in partial suppression of
      BoHV-1 replication, quantified through estimating levels of glycoprotein C mRNA
      and protein levels. Putative interactions between the mature miRNA bhv1-miR-B8-3p
      and bhv1-miR-B9 and BoHV-1 transcripts were identified providing plausible
      pathways for these molecules to affect virus replication. Therefore, these two
      miRNAs are implicated in the post-transcriptional regulation of BoHV-1
      transcripts important for virus replication and could be used to limit BoHV-1
      replication.

PMID- 30193943
TI  - Agomelatine-induced modulation of brain-derived neurotrophic factor (BDNF) in the
      rat hippocampus.
AB  - Brain-derived neurotrophic factor (BDNF) is a neurotrophin that serves as a
      survival factor for neurons. Agomelatine is a novel antidepressant as well as a
      potent agonist of melatonin (MT), MT1 and MT2 receptor types and an antagonist of
      the serotonin (5HT), 5-HT2C receptor. The study herein established whether
      treatment with agomelatine alters hippocampal BDNF protein expression under
      chronic unpredictable mild stress (CUMS) condition. Twenty-one day treatment with
      agomelatine, fluoxetine or vehicle was assessed in 52 Sprague-Dawley rats
      undergoing CUMS. Ten naive control rats were also evaluated after 21 days. The
      behavioral effects of treatments were studied using the open field test (OFT) on
      day 0, 7 and 21 and sucrose preference test on day 21. Hippocampal BDNF protein
      expression was measured using immunohistochemistry. The effect of the
      interventions on hippocampal neurons was histologically examined after H&E
      staining. Agomelatine mitigated the reduction in rearing behavior by CUMS in the
      OFT on day 7 as well as sucrose preference on day 21. The mean optical density
      value of BDNF was significantly higher in the CUMS + agomelatine group than the
      CUMS and CUMS + fluoxetine groups. The CUMS + agomelatine group had a
      significantly higher number of BDNF positive cells compared to naive controls and
      CUMS group. Histology showed that hippocampal neurons in the CUMS + agomelatine
      and CUMS + fluoxetine groups were intact and few of them demonstrated
      karyopyknosis. Agomelatine-a novel antidepressant, but not fluoxetine, increased
      hippocampal BDNF level and of BDNF positive neurons in rats subject to CUMS.

PMID- 30193944
TI  - Forced overexpression of FBP1 inhibits proliferation and metastasis in
      cholangiocarcinoma cells via Wnt/beta-catenin pathway.
AB  - AIM: To investigate the effect of fructose-1,6-bisphosphatase 1 (FBP1) on the
      malignant phenotypes of cholangiocarcinoma (CCA) cells, and to explore the
      underlying mechanism. MAIN METHODS: The expression of FBP1 in clinical CCA
      tissues was detected by real-time PCR, Western blot and immunohistochemistry
      staining. FBP1 was overexpressed by transfection of a forced expression plasmid.
      MTT, plate colony formation assay, Hoechst staining, flow cytometry, Western
      blot, wound healing, transwell assays and xenograft were performed to detect the
      growth, proliferation, cell cycle, apoptosis, migration, invasion and
      tumorigenesis in RBE and HCCC-9801 cells. In addition, the Wnt/beta-catenin
      signaling was detected. KEY FINDINGS: FBP1 was downregulated in clinical CCA
      specimens and cell lines, compared to paired para-carcinoma tissues or normal
      cholangetic epithelial cells. Gain-of-function experiments demonstrated that the
      forced expression of FBP1 inhibited the proliferation, colony formation, and
      blocked cell cycle of RBE and HCCC-9801 cells. Apoptosis of CCA cells was
      significantly enhanced by FBP1 overexpression, evidenced by upregulation of
      cleaved caspase-3, cleaved PARP and Bax levels, while downregulation of Bcl-2
      level. Moreover, overexpression of FBP1 decreased the migratory and invasive
      ability in RBE and HCCC-9801 cells. However, FBP1-induced phenotypic changes were
      eliminated by overexpression of beta-catenin. Finally, the forced overexpression
      of FBP1 inhibited tumorigenesis in vivo. SIGNIFICANCE: Our findings demonstrate
      that FBP1 is downregulated in CCA tissues and cell lines, and the overexpression
      of FBP1 inhibits the proliferation, migration, invasion and tumorigenesis of CCA
      cells partly via inactivation of Wnt/beta-catenin pathway. FBP1 may be a novel
      early diagnosis marker and therapeutic target for CCA.

PMID- 30193946
TI  - Revealing the needs of children with tracheostomies.
AB  - INTRODUCTION: Small children with tracheostomy are at potential risk and have
      very specific needs. International literature describes the need for tracheostomy
      in 0.5% to 2% of children following intubation. Reports of children submitted to
      tracheostomy, their characteristics and needs are limited in developing countries
      and therefore there is a lack of health programs and government investment
      directed to medical and non-medical care of these patients. The aim of this study
      was to describe the characteristics of these children and identify problems
      related to or caused by the tracheostomy. METHODS: A retrospective cohort study
      was performed based on a common database applied in four high complexity
      healthcare facilities to children submitted to tracheostomy from January 2013 to
      December 2015. Data concerning children's demographics, indication for
      tracheostomy, early and late complications related to tracheostomy, airway
      diagnosis, comorbidities and decannulation rates are reported. Patients who did
      not present a complete database or had a follow-up of less than six months were
      excluded. RESULTS: A total of 160 children submitted to tracheostomy during the
      three-year period met the criteria and were enrolled in this study. Median age at
      tracheostomy was 6.9 months (ranging from 1 month to 16 years, interquartile
      range of 26 months). Post-intubation laryngitis was the most frequent indication
      (48.8%). Comorbidities were frequent: neurologic disorders were reported in 40%,
      pulmonary pathologies in 26.9% and 20% were premature infants. Syndromic children
      were 23.1% and the most frequent was Down's syndrome. The most common early
      complication was infection that occurred in 8.1%. Stomal granulomas were the most
      frequent late complication and occurred in 16.9%. Airway anomalies were
      frequently diagnosed in follow-up endoscopic evaluations. Subglottic stenosis was
      the most frequent airway diagnosis and occurred in 29.4% of the cases followed by
      laryngomalacia, suprastomal collapse and vocal cord paralysis. Decannulation was
      achieved in 22.5% of the cases in the three-year period. The main cause for
      persistent tracheostomy was the need for further treatment of airway pathology.
      Mortality rate was 18.1% during this period but only 1.3% were directly related
      to the tracheostomy, the other deaths were a consequence of other comorbidities.
      CONCLUSION: Tracheostomies were performed mostly in very small children and
      comorbidities were very common. Once a tracheostomy was performed in a child in
      most cases it was not removed before a year. The most common early complication
      was stoma infection followed by accidental decannulation. The most frequent late
      complication was granuloma and suprastomal collapse. Airway abnormalities were
      very frequent in this population and therefore need to be assessed before
      attempting decannulation.

PMID- 30193945
TI  - TET2 facilitates PPARgamma agonist-mediated gene regulation and insulin
      sensitization in adipocytes.
AB  - : Emerging evidence indicates that epigenetic mechanisms like DNA methylation
      directly contribute to metabolic regulation. For example, we previously
      demonstrated that de novo DNA methyltransferase Dnmt3a plays a causal role in the
      development of adipocyte insulin resistance. Recent studies suggest that DNA
      demethylation plays an important role in the developmental process of adipocytes.
      However, little is known about whether DNA demethylase ten-eleven translocation
      (TET) proteins regulate the metabolic functions of adipocytes. METHODS: The
      expression of Tet genes was assessed in the fractionated adipocytes of chow- and
      high fat diet-fed C57/Bl6 mice using qPCR and western blotting. The effect of
      Tet2 gain- or loss-of-function in fully mature 3T3-L1 adipocytes in the
      presence/absence of Rosiglitazone (Rosi) and TNF-alpha on insulin sensitivity was
      using the insulin-stimulated glucose uptake and insulin signaling assays. Gene
      expression and DNA methylation analyses of PPARgamma target genes was performed
      in the same setting. In addition, PPARgamma reporter assays, co
      immunoprecipitation assays, PPARgamma ChIP-PCR analyses were performed. RESULTS:
      We found that adipose expression of TET2, alone among its family members, was
      significantly reduced in diet-induced insulin resistance. TET2 gain-of-function
      was sufficient to promote insulin sensitivity while loss-of-function was
      necessary to facilitate insulin sensitization in response to the PPARgamma
      agonist Rosiglitazone (Rosi) in cultured adipocytes. Consistent with this, TET2
      was required for Rosi-dependent gene activation of certain PPARgamma targets
      accompanied by changes in DNA demethylation at the promoter regions. Furthermore,
      TET2 was necessary to sustain PPARgamma binding to target loci upon activation
      with Rosi via physical interaction with PPARgamma. CONCLUSIONS: Our data
      demonstrate that TET2 works as an epigenetic regulator of Rosi-mediated insulin
      sensitization and transcriptional regulation in adipocytes.

PMID- 30193947
TI  - Perioperative and Periprocedural Management of Antithrombotic Therapy.

PMID- 30193948
TI  - Graphical Analysis Methods in Obstructive Spirometry: Does a Picture Speak More
      Than a Thousand Words?

PMID- 30193949
TI  - "Respiratory Pattern" or Where the Capitan Rules a Sailor has no Sway?

PMID- 30193950
TI  - Examining Motor Tasks of Differing Complexity After Concussion in Adolescents.
AB  - OBJECTIVES: (1) To determine the effects of concussion-related motor impairments
      at different task complexities in isolation and with a cognitive dual-task and
      (2) to determine if self-reported balance deficits after concussion are
      associated with gait, quiet stance, or cognitive dual-task impairments. DESIGN:
      Cross-sectional study. SETTING: Sports medicine clinic. PARTICIPANTS: Adolescent
      athletes clinically diagnosed with a sport-related concussion and those without
      concussion. Forty-nine patients with concussion (mean age=14.9+/-1.9y; 51%
      female; tested 7.0+/-3.0d postinjury) and 65 control participants (mean
      age=14.9+/-1.6y; 52% female) completed the study (N=114). INTERVENTIONS: Athletes
      with concussion completed a single-task and dual-task standing and walking
      protocol within 14 days of injury and were compared to those without concussion.
      MAIN OUTCOME MEASURES: Outcome measures included gait speed, quiet stance (root
      mean square [RMS] coronal/sagittal plane sway), and cognitive performance
      (accuracy). Dual-task costs were calculated as the percentage change between
      single-task and dual-task conditions. Participants with concussion were then
      stratified by those who did and did not report subjective balance problems at the
      time of testing and compared using objective balance and gait metrics. RESULTS:
      The concussion group walked slower during dual-task gait than controls (0.83+/
      0.17 m/s vs 0.92+/-0.15 m/s; Cohen's d=0.53). Dual-task quiet stance RMS sway
      values were similar for concussion and control groups in coronal (1.20+/-0.52 m/s
      2 vs 1.26+/-0.65 m/s-2; d=0.09) and sagittal (0.56+/-0.24 m/s-2 vs 0.73+/-0.44
      m/s-2; d=0.20) movement planes. The concussion participants with subjectively
      reported balance problems had significantly greater walking speed dual-task costs
      than concussion participants without self-reported balance problems (-25+/-10% vs
      -19+/-9%; P=.02). CONCLUSIONS: Following concussion, adolescents demonstrate
      slower gait speeds, but similar quiet stance values relative to those without
      concussion. The study results indicate that tasks requiring greater motor
      coordination may elicit greater alterations following a concussion.

PMID- 30193951
TI  - Effects of the Surface Texture and Weight of a Pinch Apparatus on the Reliability
      and Validity of a Hand Sensorimotor Control Assessment.
AB  - OBJECTIVES: To investigate the reliability and validity of a modified pinch
      apparatus devised with 3 surface textures and 2 different weights for clinical
      application. DESIGN: Case-controlled study. SETTING: A university hospital.
      PARTICIPANTS: The participants (N=32) included carpal tunnel syndrome (CTS)
      patients (n=16) with 20 sensory neuropathy hands, and an equal number of age-sex
      matched volunteers without CTS, as well as young volunteers without CTS (n=16
      with 20 hands) used to analyze both the testing validity and reliability of the
      modified device. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The Semmes
      Weinstein monofilament (SWM) and two-point discrimination (2PD) tests were
      conducted, and the force ratio between the FPpeak (peak pinch force during
      lifting phase) and FLmax (maximum load force at maximum upward acceleration
      onset) detected from a pinch-holding-up activity (PHUA) under various testing
      conditions was obtained. RESULTS: The range of the intraclass correlation
      coefficient of this pinch device was 0.369-0.952. The CTS patients exhibited
      poorer force modulation ability according to the inertial change in a dynamic
      lifting task when compared to the controls under all testing conditions (P<.001).
      The area under the receiver operating characteristic force ratio curve was 0.841,
      revealing high accuracy of the test for diagnosing CTS neuropathic hands under
      the testing condition in which the 125-g coarse texture device was used. In
      addition, the weight factor was shown to have significant effects on the
      sensitivity and accuracy of the PHUA assessment. CONCLUSIONS: This study showed
      that the PHUA test via the modified pinch apparatus is a sensitive tool that can
      be used in clinical practice for detecting neuropathic CTS hands. In addition,
      changing the weight of the pinch device has a significant effect on the
      sensitivity and accuracy of the PHUA assessment.

PMID- 30193952
TI  - Serum-derived IgG from coxsackievirus A6-infected patients can enhance the
      infection of peripheral blood mononuclear cells with coxsackievirus A6.
AB  - Coxsackievirus A6 (CV-A6) has recently emerged as an enterovirus causing Hand
      Foot and Mouth Disease with severe complications. The pathogenic mechanisms of CV
      A6- associated Hand foot and Mouth disease are largely unknown. In this study, it
      was investigated whether serum and IgG from patients with CV-A6 infection can
      enhance the infection of PBMC with the virus. Serum samples were obtained from
      five children with CV-A6 infection confirmed by RT-PCR and seven controls. IgG
      was isolated from serum by using affinity chromatography columns. CV-A6 was
      incubated with serum or IgG from controls and patients then the mixtures were
      added to PBMC cultures. The levels of IFNalpha in supernatants were measured by
      ELISA, and the levels of intracellular viral RNA were measured by RT-qPCR. It has
      been observed that there is an anti-CV-A6 enhancing activity in serum and serum
      derived immunoglobulin G of children with CV-A6 infection but not in those of
      uninfected controls. Whether this activity has implications in the pathogenesis
      of CV-A6 associated diseases should be investigated.

PMID- 30193953
TI  - Exploring the sensitivity of magnetic resonance fingerprinting to motion.
AB  - PURPOSE: To explore the motion sensitivity of magnetic resonance fingerprinting
      (MRF), we performed experiments with different types of motion at various time
      intervals during multiple scans. Additionally, we investigated the possibility to
      correct the motion artifacts based on redundancy in MRF data. METHODS: A radial
      version of the FISP-MRF sequence was used to acquire one transverse slice through
      the brain. Three subjects were instructed to move in different patterns (in-plane
      rotation, through-plane wiggle, complex movements, adjust head position, and
      pretend itch) during different time intervals. The potential to correct motion
      artifacts in MRF by removing motion-corrupted data points from the fingerprints
      and dictionary was evaluated. RESULTS: Morphological structures were well
      preserved in multi-parametric maps despite subject motion. Although the bulk T1
      values were not significantly affected by motion, fine structures were blurred
      when in-plane motion was present during the first part of the scan. On the other
      hand, T2 values showed a considerable deviation from the motion-free results,
      especially when through-plane motion was present in the middle of the scan (-44%
      on average). Explicitly removing the motion-corrupted data from the scan
      partially restored the T2 values (-10% on average). CONCLUSION: Our experimental
      results showed that different kinds of motion have distinct effects on the
      precision and effective resolution of the parametric maps measured with MRF.
      Although MRF-based acquisitions can be relatively robust to motion effects
      occurring at the beginning or end of the sequence, relying on redundancy in the
      data alone is not sufficient to assure the accuracy of the multi-parametric maps
      in all cases.

PMID- 30193954
TI  - Efficient segmentation and correction model for brain MR images with level set
      framework based on basis functions.
AB  - With the wide application of MR images to detect disease in human's brain deeply,
      the shortcomings of the technology are necessarily waiting to be solved. For
      example, MR images always show serious intensity inhomogeneity called the bias
      field, which may prevent to deduce exact analysis of images. To eliminate the
      distraction, many methods are proposed. Though experimental results already have
      stood for the advantages of those methods, there are still lots of problems that
      cannot be neglected, such as bad segmentation, wrong correction and over
      correction which has not attracted much attention yet. Among all those methods,
      the multiplicative intrinsic component optimization (MICO) model influenced us
      more. Based on the MICO model and split Bregman method, in this paper, we put
      forward a new model to segment and correct bias field moderately and
      simultaneously for MR images. Then, we applied our model to a large quantity of
      MR images, and gained lots of expected results. For a better observation, we
      compared our model with the MICO model in both segmentation and bias correction
      results, it can be seen from the experimental results that our model has
      performed well for the challenging intensity inhomogeneity problems. Many good
      characteristics like accuracy, efficiency and robustness also have been exhibited
      in numerical results and comparisons with the MICO model.

PMID- 30193955
TI  - Evolutionary stability of ideal free dispersal under spatial heterogeneity and
      time periodicity.
AB  - Roughly speaking, a population is said to have an ideal free distribution on a
      spatial region if all of its members can and do locate themselves in a way that
      optimizes their fitness, allowing for the effects of crowding. Dispersal
      strategies that can lead to ideal free distributions of populations using them
      have been shown to exist and to be evolutionarily stable in a number of modeling
      contexts in the case of habitats that vary in space but not in time. Those
      modeling contexts include reaction-diffusion-advection models and the analogous
      models using discrete diffusion or nonlocal dispersal described by integro
      differential equations. Furthermore, in the case of reaction-diffusion-advection
      models and their nonlocal analogues, there are strategies that allow populations
      to achieve an ideal free distribution by using only local information about
      environmental quality and/or gradients. We show that in the context of reaction
      diffusion-advection models for time-periodic environments with spatially varying
      resource levels, where the total level of resources in an environment remains
      fixed but its location varies seasonally, there are strategies that allow
      populations to achieve an ideal free distribution. We also show that those
      strategies are evolutionarily stable. However, achieving an ideal free
      distribution in a time-periodic environment requires the use of nonlocal
      information about the environment such as might be derived from experience and
      memory, social learning, or genetic programming.

PMID- 30193956
TI  - Mst1 knockout enhances cardiomyocyte autophagic flux to alleviate angiotensin II
      induced cardiac injury independent of angiotensin II receptors.
AB  - AIMS: Angiotension II (Ang II) plays a central role in the pathogenesis of renin
      angiotensin-aldosterone system (RAAS)-induced heart failure. Mst1 exerts its
      function in cardiomyocytes subjected to pathological stimuli via inhibiting
      autophagy and aggravating apoptosis, but its role in RAAS-mediated cardiac injury
      is still unknown. Here, we aimed to determine whether cardiomyocyte-specific Mst1
      knockout can alleviate Ang II-induced cardiac injury by improving cardiomyocyte
      autophagy and whether these functions depend on Ang II receptors. RESULTS: Mst1
      knockout alleviated Ang II-induced heart failure, without affecting blood
      pressure and compensatory concentric hypertrophy. Mst1 specific knockout improved
      the effects of Ang II on cardiomyocyte autophagy, as evidenced by further
      increased LC3-II expression and decreased P62 expression. More typical
      autophagosomes accompanied by less damaged mitochondria were also observed by
      electron microscopy in Ang II-treated Mst1Delta/Delta mice. In vitro, Mst1
      knockdown promoted cardiomyocyte autophagic flux, as demonstrated by more GFP
      mRFP-LC3 puncta per cell. Increased LC3-II and decreased P62 expression both in
      the presence and absence of chloroquine were observed in Mst1 knockdown
      cardiomyocytes administered with Ang II. Treatment with 3-MA, an inhibitor of
      autophagy, abolished the beneficial effects of Mst1 knockout against Ang II
      induced cardiac dysfunction. The compensatory effects of Ang II on upregulated
      autophagy were associated with Mst1 inhibition. Interestingly, the knockdown or
      antagonization of AT1R inhibited cardiomyocyte autophagy, which may represent a
      threat to cardiac function. Importantly, Mst1 knockout consistently enhanced
      cardiomyocyte autophagy following the knockdown or blocking of AT1R and AT2R.
      CONCLUSION: Cardiomyocyte-specific Mst1 knockout alleviates Ang II-induced
      cardiac injury by enhancing cardiomyocyte autophagy. Mst1 inhibition may
      counteract the undesirable effects of Ang II receptors blockage on cardiomyocyte
      autophagy and represent a promising complementary treatment strategy against Ang
      II-induced cardiac injury.

PMID- 30193958
TI  - Reduction of cardiac TGFbeta-mediated profibrotic events by inhibition of Hsp90
      with engineered protein.
AB  - Myocardial fibroblast activation coupled with extracellular matrix production is
      a pathological signature of myocardial fibrosis and is governed mainly by
      transforming growth factor TGFbeta-Smad2/3 signaling. Targeting the ubiquitous
      TGFbeta leads to cellular homeostasis deregulation with adverse consequences. We
      previously showed the anti-fibrotic effects upon downregulation of 90-kDa heat
      shock protein (Hsp90), a chaperone that associates to the TGFbeta signaling
      cascade. In the present study, we use a fluorescent-labeled Hsp90 protein
      inhibitor (CTPR390-488) with specific Hsp90 binding properties to reduce
      myocardial pro-fibrotic events in vitro and in vivo. The mechanism of action
      involves the disruption of TGFbetaRI-Hsp90 complex, resulting in a decrease in
      TGFbeta signaling and reduction in extracellular matrix collagen. In vivo,
      decreased myocardial collagen deposition was observed upon CTPR390-488 treatment
      in a pro-fibrotic mouse model. This is the first study demonstrating the ability
      of an engineered Hsp90 protein inhibitor to block collagen expression, reduce the
      motility of myocardial TGFbeta-activated fibroblasts and ameliorate angiotensin
      II induced cardiac myocardial fibrosis in vivo.

PMID- 30193957
TI  - Differential Wnt-mediated programming and arrhythmogenesis in right versus left
      ventricles.
AB  - Several inherited arrhythmias, including Brugada syndrome and arrhythmogenic
      cardiomyopathy, primarily affect the right ventricle and can lead to sudden
      cardiac death. Among many differences, right and left ventricular cardiomyocytes
      derive from distinct progenitors, prompting us to investigate how embryonic
      programming may contribute to chamber-specific conduction and arrhythmia
      susceptibility. Here, we show that developmental perturbation of Wnt signaling
      leads to chamber-specific transcriptional regulation of genes important in
      cardiac conduction that persists into adulthood. Transcriptional profiling of
      right versus left ventricles in mice deficient in Wnt transcriptional activity
      reveals global chamber differences, including genes regulating cardiac
      electrophysiology such as Gja1 and Scn5a. In addition, the transcriptional
      repressor Hey2, a gene associated with Brugada syndrome, is a direct target of
      Wnt signaling in the right ventricle only. These transcriptional changes lead to
      perturbed right ventricular cardiac conduction and cellular excitability. Ex vivo
      and in vivo stimulation of the right ventricle is sufficient to induce
      ventricular tachycardia in Wnt transcriptionally inactive hearts, while left
      ventricular stimulation has no effect. These data show that embryonic
      perturbation of Wnt signaling in cardiomyocytes leads to right ventricular
      arrhythmia susceptibility in the adult heart through chamber-specific regulation
      of genes regulating cellular electrophysiology.

PMID- 30193959
TI  - Bacteroides thetaiotaomicron.
AB  - This infographic on Bacteroides thetaiotaomicron (Bt) explores the ability of
      this microbe to digest a broad array of complex carbohydrates, alter its surface
      features, and its emerging role in gastrointestinal diseases. The infographic of
      Bacteroides thetaiotaomicron (Bt) illustrates two key facets of its symbiotic
      lifestyle in the human gut: a broad ability to digest dietary fiber
      polysaccharides and host glycans, and a dynamic cell-surface architecture that
      promotes both interactions with and evasion of the host immune system. The starch
      utilization system (Sus) is a cell-surface and periplasmic system involved in
      starch cleavage and transport. Over 80 additional Sus-like systems utilize
      substrates ranging from host glycans to plant cell wall pectins. Bt has evolved
      intricate strategies to interact with other microbes or its host, including
      modification of its surface. Some nutrient utilization pathways select for or
      directly trigger changes in capsular polysaccharide (CPS) expression. Like other
      fermentative members of the gut microbiome, Bt produces host absorbable short
      chain and organic acids, which can all be absorbed by the host as a source of
      energy.

PMID- 30193961
TI  - An integrated study on TFs and miRNAs in colorectal cancer metastasis and
      evaluation of three co-regulated candidate genes as prognostic markers.
AB  - Molecular alterations that occur in cancer have the potential to be considered as
      either cancer biomarkers or targeted therapies or even both. In the presented
      study, we aimed to elucidate the gene regulatory network of metastatic colorectal
      cancer using data acquired from microarrays to reach the most common DEGs in
      colorectal cancer metastasis and find their possible regulatory mechanism by
      DETFs and DEmiRs. In this regards, seven microarray datasets were employed to
      assess the most important DEGs, DETFs and DEmiRs in colorectal cancer metastasis.
      Afterward, GRN based on DETFs and DEmiRs were constructed. Also ARACNE algorithm
      was used to construct an accurate GRN. GRN was analyzed structurally and then,
      two DETFs (LEF1 and ETV4) and a less-well known DEG (FABP6) by real time qRT-PCR
      in 50 patients with colorectal cancer were quantified. The constructed GRN
      highlighted the importance of some DETFs and DEmiRs in colorectal cancer
      metastasis. Interestingly the gene expression analysis by qRT-PCR on three
      candidate genes (LEF1, ETV4 and FABP6) indicated that the three genes were co
      expressed in tumor samples, and were significantly associated with metastasis in
      colorectal cancer. Therefore, our experimental results proved a part of our
      comprehensive data analysis and system biology results. In summary, according to
      our empirical study we found the importance of three candidate genes as the
      potent prognostic factors in colorectal cancer metastasis. Also our study in a
      holistic insight on gene regulatory mechanism revealed the importance of some
      gene regulatory factors (DETFs and DEmiRs) and their potential as prognostic
      factors and/or targets in molecular targeted therapies in colorectal cancer.

PMID- 30193962
TI  - Primary biliary cholangitis: A tale of epigenetically-induced secretory failure?
AB  - Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease
      associated with autoimmune-related destruction of small to medium size
      intrahepatic bile ducts. The aetiology of PBC is unknown and its pathogenesis
      remains obscure. Both genetic variants and environmental factors have been linked
      to increased PBC susceptibility, with other alterations known to cooperate in
      disease pathobiology. Increasing evidence indicates the presence of epigenetic
      abnormalities in PBC, particularly alterations of cholangiocellular microRNAs
      (miRNAs or miRs). This review highlights and discusses the most relevant
      epigenetic alterations found in patients with PBC, focusing on the role of miR
      506 in the promotion of cholestasis and immune activation.

PMID- 30193960
TI  - From Theory to Practice: Translating Whole-Genome Sequencing (WGS) into the
      Clinic.
AB  - Hospitals worldwide are facing an increasing incidence of hard-to-treat
      infections. Limiting infections and providing patients with optimal drug regimens
      require timely strain identification as well as virulence and drug-resistance
      profiling. Additionally, prophylactic interventions based on the identification
      of environmental sources of recurrent infections (e.g., contaminated sinks) and
      reconstruction of transmission chains (i.e., who infected whom) could help to
      reduce the incidence of nosocomial infections. WGS could hold the key to solving
      these issues. However, uptake in the clinic has been slow. Some major scientific
      and logistical challenges need to be solved before WGS fulfils its potential in
      clinical microbial diagnostics. In this review we identify major bottlenecks that
      need to be resolved for WGS to routinely inform clinical intervention and discuss
      possible solutions.

PMID- 30193963
TI  - A Systematic Review and Meta-Analysis of the Effectiveness of Surgical
      Decompression in Treating Patients with Malignant Middle Cerebral Artery
      Infarction.
AB  - BACKGROUND: Malignant infarction of the middle cerebral artery (MCI) is life
      threatening. It is associated with a mortality as high as 80%, and survival often
      at the expense of serious disability. Limited success of medical therapies has
      resulted in decompressive craniectomy (DC) being increasingly used as a treatment
      for MCI, although evidence of its efficacy is inconclusive. In this study, the
      efficacy of DC in improving survival, or survival free of severe disability, was
      assessed. METHODS: A meta-analysis was performed to approximate the efficacy of
      DC for treating MCI, considering age and time to surgery. A systematic literature
      review was conducted on Medline, Embase, and Cochrane library databases to August
      1, 2018. Death and severe disability at 3, 6, 12, and 36 months follow-up were
      assessed, comparing best medical therapy with DC. RESULTS: 18 studies were
      eligible for inclusion and represented 987 individuals who received DC. Nine of
      these were randomized controlled trials (RCTs) (n = 374 DC). Early DC (<48 hours
      from onset of stroke) reduced mortality (odds ratio [OR] = 0.18, 95% confidence
      interval [CI] = 0.11, 0.29; P < 0.00001) but not unfavourable outcome (modified
      Rankin Scale [mRS] >4) (OR = 1.38, 95% CI = 0.47, 4.11; P = 0.56) at 12 months
      follow-up. This survival benefit was maintained regardless of age. CONCLUSION:
      Early DC reduces mortality but does not appear to improve favourable outcomes in
      patients younger or older than 60 years after MCI. RCTs incorporating quality of
      life assessments are warranted for MCI patients, in addition to defining the
      optimal timing and benefits of DC in older patients.

PMID- 30193964
TI  - Transoral Endoscopic Resection of High Cervical Osteophytes with Long-Term
      Symptom Resolution: Case Series, Imaging, and Literature Review.
AB  - BACKGROUND: Anterior cervical osteophytes (ACOs) are a common radiologic finding
      in the elderly; rarely, they can cause dysphagia, dysphonia, and dyspnea.
      Symptomatic ACOs are most commonly found between C4 and C7 and much less commonly
      at higher cervical levels. Here, we present a case series, with an example case
      of a 57-year-old woman with high cervical osteophytes at C1-C2 causing globus
      sensation, dysphagia, and dysphonia. Additionally, we provide a literature review
      regarding the causes, diagnosis, and treatment of ACOs, with a focus on
      management of high ACOs. CASE DESCRIPTION: A 57-year-old smoker with a history of
      chronic neck pain and previous cervical spinal instrumentation presented with
      several months of globus sensation, dysphagia, and dysphonia. Imaging revealed 2
      large anterior osteophytes at C1-C2. She underwent endoscopic transoral
      osteophytectomy, with resolution of symptoms. Five other patients are also
      presented who underwent similar procedures. CONCLUSIONS: ACOs are a potential
      cause of dysphagia, and their diagnosis is best made with computed tomographic
      imaging and oropharyngeal swallow study. Although high ACOs at C1-C2 are a rare
      finding, here we show with an exemplary case and small case series that they can
      be effectively treated with transoral endoscopic osteophytectomy.

PMID- 30193965
TI  - Natural deep eutectic solvents for lignocellulosic biomass pretreatment: Recent
      developments, challenges and novel opportunities.
AB  - Conversion of lignocellulosic biomass to fuels and chemicals has attracted
      immense research and development around the world. Lowering recalcitrance of
      biomass in a cost-effective manner is a challenge to commercialize biomass-based
      technologies. Deep eutectic solvents (DESs) are new 'green' solvents that have a
      high potential for biomass processing because of their low cost, low toxicity,
      biodegradability, easy recycling and reuse. This article discusses the properties
      of DESs and recent advances in their application for lignocellulosic biomass
      processing. The effectiveness of DESs in hydrolyzing lignin-carbohydrate
      complexes, removing lignin/hemicellulose from biomass as well as their effect on
      biomass deconstruction, crystallinity and enzymatic digestibility have been
      discussed. Moreover, this review presents recent findings on the compatibility of
      natural DESs with enzymes and microorganisms.

PMID- 30193967
TI  - Reply to Zhenjie Wu and Linhui Wang's Letter to the Editor re: Riccardo Bertolo,
      Riccardo Autorino, Giuseppe Simone, et al. Outcomes of Robot-assisted Partial
      Nephrectomy for Clinical T2 Renal Tumors: A Multicenter Analysis (ROSULA
      Collaborative Group). Eur Urol 2018;74:226-32.

PMID- 30193966
TI  - Real time detection of glutathionse in chemotherapy squamous-cell carcinoma cells
      of a fluorescent probe.
AB  - Glutathione (GSH) plays a key role in protecting damage induced by radiation and
      chemotherapy drugs. Current methods, which quantify GSH level changes by using
      cellular extraction or being based on redox homeostasis results, are unable to
      directly measure real time GSH level in live cells. In this article, we utilized
      a newly designed reversible fluorescent probe to measure GSH in living cells. The
      image of probe 1 can reveal intracellular GSH location and GSH level changes
      caused by different chemotherapy drugs in squamous-cell carcinoma cells. The
      results show that it is the first report with probe 1 that to quantify real-time
      GSH level changes in the cultured chemotherapy cancer cells and different changes
      in GSH level that may confer chemotherapy resistance.

PMID- 30193968
TI  - Re: Riccardo Bertolo, Riccardo Autorino, Giuseppe Simone, et al. Outcomes of
      Robot-assisted Partial Nephrectomy for Clinical T2 Renal Tumors: A Multicenter
      Analysis (ROSULA Collaborative Group). Eur Urol 2018;74:226-32.

PMID- 30193969
TI  - Embodied Motherhood: Exploring Body Image in Pregnant and Parenting Youth.
AB  - STUDY OBJECTIVE: There is a paucity of research on body image in pregnant and
      parenting youth (PPY). Study objectives were to examine: (1) profiles of PPY
      regarding body image, depression, and eating behaviors and any effects of age and
      pregnancy status on results; and (2) PPY perceptions of body image. DESIGN,
      SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: Demographic data
      and scores from measures related to self-esteem, body esteem, eating behaviors,
      and depression were collected from 101 PPY from 2 urban centers. Two focus group
      sessions were held to further explore survey findings. Sessions were audio
      recorded and transcribed verbatim for analysis. RESULTS: Participants (mean age,
      19.8 years) reported a history of depression (79/101; 78.2%), anxiety (75/101;
      74.3%), drug/alcohol abuse (45/101; 44.6%), and eating disorder (32/101; 31.7%).
      Parenting (nonpregnant; n = 64) participants had lower body esteem (P = .041) and
      more eating disorder behaviors (P = .026) compared with pregnant (n = 37)
      participants. A history of depression or eating disorder both independently
      increased risk for lower body esteem and self-esteem and higher depressive
      symptoms in pregnant youth. Four dominant themes emerged from qualitative data:
      (1) adapting to rapidly changing bodies; (2) inter-relationship between body
      image and mood; (3) added attention and perceptions of pressure to return to
      prepregnancy body size; and (4) reconciling change and striving to find a new
      normal. CONCLUSION: This study highlights the importance of exploring past and
      current body image, mood, and eating disorder behavior in PPY for risk of current
      mental health issues. Future research exploring prepregnancy depression, eating
      disorder, body esteem, and depression in pregnant youth are needed.

PMID- 30193970
TI  - Venous Thromboembolism in Minimally Invasive Gynecologic Surgery: A Systematic
      Review.
AB  - Venous thromboembolism (VTE) is the leading cause of preventable healthcare
      related death after surgery. Although there is a large body of research on VTE in
      the general population as well as risk-assessment tools, evidence specific to the
      current practices in gynecologic surgery is more sparse. This review article
      seeks to discuss current literature on VTE in gynecologic surgery, with a focus
      on minimally invasive surgery. Evidence on risk factors for VTE in gynecologic
      surgery is evaluated as well as current recommendations use of thromboprophylaxis
      for prevention of VTE. Despite data showing that minimally invasive gynecologic
      surgery independently decreases risk of VTE compared with laparotomy, current
      clinical risk assessment tools and guidelines do not incorporate mode of surgery
      into recommendations for perioperative VTE prevention.

PMID- 30193971
TI  - Ovarian Reserve Following Laparoscopic Ovarian Cystectomy vs Cyst Deroofing for
      Endometriomas.
AB  - STUDY OBJECTIVE: Because laparoscopic ovarian cystectomy of endometriomas is
      known to adversely impact patient ovarian reserve, the search for other
      techniques of surgical management is ongoing. The present study was undertaken to
      evaluate laparoscopic cyst deroofing as a feasible alternative. STUDY DESIGN:
      Prospective, randomized clinical trial (Canadian Task Force classification I).
      SETTING: University maternity hospital. PATIENTS: Women diagnosed with unilateral
      or bilateral ovarian endometriomas. INTERVENTIONS: Patients were managed with
      either laparoscopic ovarian cystectomy or cyst deroofing. MEASUREMENTS AND MAIN
      RESULTS: A total of 122 women with endometriomas were randomized to either
      laparoscopic cystectomy (group 1) or laparoscopic cyst deroofing (group 2). The
      primary endpoint was the effect on ovarian reserve based on changes in anti
      Mullerian hormone (AMH) values. At 1 month postsurgery, anti-Mullerian hormone
      values were significantly decreased (p < .001) from preoperative values, from
      4.25 +/- 0.87ng/mL to 1.66 +/- 1.02ng/mL in group 1 and from 4.2 +/- 1.69ng/mL to
      2.15 +/- 1.48ng/mL in group 2. In addition, antral follicle count and ovarian
      volume decreased significantly (p < .001) in both groups by 1 month postsurgery.
      The decreases in these 3 parameters were more significant (p < .001) in group 1
      than in group 2. CONCLUSION: Laparoscopic cyst deroofing of endometriomas appears
      to be a promising alternative to laparoscopic cystectomy, with less postoperative
      decrease in ovarian reserve; however, the higher rate of endometrioma recurrence
      warrants future clinical research to determine the optimal surgical management of
      endometriomas.

PMID- 30193972
TI  - Laparoscopic Removal of a Dislocated Screw of a Hip Joint Endoprosthesis during
      Oncologic Surgery.

PMID- 30193973
TI  - Enhanced action performance following TMS manipulation of associative plasticity
      in ventral premotor-motor pathway.
AB  - Skillful goal-directed manual actions such as grasping and manipulating objects
      are supported by a large sensorimotor network. Within this network, the ventral
      premotor cortex (PMv) transforms visual information about objects into motor
      commands that are conveyed to the primary motor cortex (M1), allowing fine
      control of finger movements. However, it is unknown whether transcranial magnetic
      stimulation (TMS) of this PMv-to-M1 hierarchical pathway improves action
      performance. To fill in this gap, here, we used cortico-cortical paired
      associative stimulation (ccPAS) with the aim of manipulating synaptic efficacy in
      the human PMv-to-M1 pathway. We found that repeatedly pairing TMS of pre-and post
      synaptic nodes of the PMv-to-M1 pathway (i.e., PMv-to-M1 ccPAS) increased motor
      excitability and enhanced performance on the 9-Hole Peg Test (9-HPT), which taps
      into PMv-M1 functioning. These effects were specific to the ccPAS protocol
      consistent with the direction of the PMv-to-M1 hierarchy, as no effects were
      observed when reversing the order of the paired TMS pulses (i.e., following a M1
      to-PMv ccPAS) or when administering sham ccPAS. Additionally, the effect of PMv
      to-M1 ccPAS appeared functionally specific, as no behavioral enhancement was
      observed in a visuomotor control task. We therefore provide novel causal evidence
      that the PMv-to-M1 pathway, which is instrumental to object-oriented hand
      actions, is sensitive to TMS manipulations of associative plasticity. Our study
      highlights the causal role of the PMv-to-M1 pathway in controlling skillful
      object-oriented hand actions and suggests that ccPAS might be a useful tool for
      investigating the functional relevance of directional connectivity in humans.
      These findings may have implications for designing novel therapeutic strategies
      based on the manipulation of associative plasticity in cortico-cortical networks.

PMID- 30193974
TI  - Sparse wars: A survey and comparative study of spherical deconvolution algorithms
      for diffusion MRI.
AB  - Spherical deconvolution methods are widely used to estimate the brain's white
      matter fiber orientations from diffusion MRI data. In this study, eight spherical
      deconvolution algorithms were implemented and evaluated. These included two model
      selection techniques based on the extended Bayesian information criterion (i.e.,
      best subset selection and the least absolute shrinkage and selection operator),
      iteratively reweighted l2- and l1-norm approaches to approximate the l0-norm,
      sparse Bayesian learning, Cauchy deconvolution, and two accelerated Richardson
      Lucy algorithms. Results from our exhaustive evaluation show that there is no
      single optimal method for all different fiber configurations, suggesting that
      further studies should be conducted to find the optimal way of combining
      solutions from different methods. We found l0-norm regularization algorithms to
      resolve more accurately fiber crossings with small inter-fiber angles. However,
      in voxels with very dominant fibers, algorithms promoting more sparsity are less
      accurate in detecting smaller fibers. In most cases, the best algorithm to
      reconstruct fiber crossings with two fibers did not perform optimally in voxels
      with one or three fibers. Therefore, simplified validation systems as employed in
      a number of previous studies, where only two fibers with similar volume fractions
      were tested, should be avoided as they provide incomplete information. Future
      studies proposing new reconstruction methods based on high angular resolution
      diffusion imaging data should validate their results by considering, at least,
      voxels with one, two, and three fibers, as well as voxels with dominant fibers
      and different diffusion anisotropies.

PMID- 30193975
TI  - Angular resolution enhancement technique for diffusion-weighted imaging (DWI)
      using predicted diffusion gradient directions.
AB  - Anisotropic diffusion MRI techniques using single-shell or multi-shell
      acquisitions have been proposed as a means to overcome some limitations imposed
      by diffusion tensor imaging (DTI), especially in complex models of fibre
      orientation distribution in voxels. A long acquisition time for the angular
      resolution of diffusion MRI is a major obstacle to practical clinical
      implementations. In this paper, we propose a novel method to improve angular
      resolution of diffusion MRI acquisition using given diffusion gradient (DG)
      directions. First, we define a local diffusion pattern map of diffusion MR
      signals on a single shell in given DG directions. Using the local diffusion
      pattern map, we design a prediction scheme to determine the best DG direction to
      be synthesized within a nearest neighborhood DG directions group. Second, the
      local diffusion pattern map and the spherical distance on the shell are combined
      to determine a synthesized diffusion signal in the new DG direction. Using the
      synthesized and measured diffusion signals on a single sphere, we estimate a spin
      orientation distribution function (SDF) with human brain data. Although the
      proposed method is applied to SDF, a basic idea is to increase the angular
      resolution using the measured diffusion signals in various DG directions. The
      method can be applicable to different acquired multi-shell data or diffusion
      spectroscopic imaging (DSI) data. We validate the proposed method by comparing
      the recovered SDFs using the angular resolution enhanced diffusion signals with
      the recovered SDF using the measured diffusion data. The developed method
      provides an enhanced SDF resolution and improved multiple fiber structure by
      incorporating synthesized signals. The proposed method was also applied neurite
      orientation dispersion and density imaging (NODDI) using multi-shell
      acquisitions.

PMID- 30193976
TI  - Patellofemoral joint replacement - Mean five year follow-up.
AB  - BACKGROUND: The Femoro Patella Vialli FPV is a second-generation patellofemoral
      arthroplasty implant. It is the second most commonly used patellofemoral implant
      in the National Joint Registry of England and Wales. This is the first published
      mid-term outcome series for this prosthesis. METHODS: We reviewed the outcomes
      for all patients who had patellofemoral arthroplasty. Primary outcome was the
      intention to revise the implant; secondary outcome measures were Oxford and
      Kujala outcome scores. RESULTS: A total of 43 FPV patellofemoral joint prostheses
      were implanted in 32 patients at our institution between April 2004 and December
      2012. Mean follow-up was 65 (30-119) months. Only one patient was lost to follow
      up. At final follow-up the mean flexion was 110 degrees  (85 degrees -130 degrees
      ). Five of 43 knees required revision to a total knee replacement because of
      progressive tibiofemoral osteoarthritis. Revisionswere carried out after amean of
      56 months (30-109). There was no radiographic loosening in any case. The most
      recent functional assessment showed that the mean Oxford Knee score (OKS) has
      improved from 18 (five to 35) preoperatively to 29 (nine to 45) and the Kujala
      score from 35 (five to 74) preoperatively to 58 (18-91). CONCLUSIONS: Midterm
      results with FPV prosthesis demonstrate that moderate outcomes can be achieved.
      Patellofemoral arthroplasty may be used to delay total knee replacement but
      judicious patient selection to identify truly isolated patellofemoral
      osteoarthritis is necessary. Chondral lesion in weight bearing area can lead to
      early implant failure. The main cause of failure was progressive tibiofemoral
      osteoarthritis.

PMID- 30193977
TI  - Long-term results after primary augmented repair of proximal tears of the
      anterior cruciate ligament with the Kennedy-LAD - Does it work?
AB  - BACKGROUND: The purpose of this study was to objectively evaluate the clinical
      functionality of the knee joint 30 years after surgical augmentation of the ACL
      with the "Kennedy Ligament Augmentation Device (r)" (Kennedy LAD(r)). METHODS:
      The patient collective consisted of 41 patients with an average age of 59.51
      years (+/-10.18 standard deviation). Included were all patients treated
      operatively with a Kennedy LAD(r) augmented reattachment of the ACL at the
      Department of Trauma Surgery between 1983 and 1985. The state of the knee joint
      was evaluated with the following measures: Knee injury and Osteoarthritis Outcome
      Score, Lysholm Score, Short Form (36) Health Survey, International Knee
      Documentation Committee Score (IKDC, objective + subjective form) and Tegner
      Activity Scale. RESULTS: Seven patients (17%) sustained a re-rupture of the
      Kennedy LAD(r) augmented ACL after a mean time of 16.28 years. Five of them
      underwent revision surgery. Another four patients (9.76%) showed an ACL
      insufficiency in clinical examination. The average IKDC Score was 74.14 +/-
      16.62, the average Lysholm Score was 86.83 +/- 14.10, the average Tegner Activity
      Scale was 4.34 +/- 1.11, and the average Knee injury and Osteoarthritis Outcome
      Score was 86.25 +/- 11.64 at final follow-up. The mean Kellgren Lawrence Score of
      the operated knee was 2 +/- 0.71. CONCLUSION: An overall good outcome 30 years
      after primary ACL augmented repair with the Kennedy LAD(r) with an implant
      survival rate of 73% could be reached. These results therefore support the trend
      of ACL augmentation in selected cases. LEVEL OF EVIDENCE: Retrospective study,
      Level IV.

PMID- 30193978
TI  - Glomeruli from patients with nephrin mutations show increased number of ciliated
      and poorly differentiated podocytes.
AB  - BACKGROUND: Podocytes are postmitotic, highly specialized cells which maintain
      the glomerular filtration barrier (GFB). Their injury is characterized by foot
      processes effacement and change in protein expression leading to proteinuria and
      end-stage kidney disease. METHODS: Our study focuses on the morphological and
      immunohistochemical changes of human podocytes during normal development and
      postnatal period, compared to congenital nephrotic syndrome of the Finnish type
      (CNF). Kidney tissues taken from 17 human conceptuses 8th-38th weeks old, two
      healthy and three CNF kidneys were embedded in paraffin for immunohistochemical
      or double immunofluorescence methods, or were embedded in resin for electron
      microscopy. Paraffin sections were stained with markers for proliferation (Ki
      67), proteins nephrin and nestin, and alpha-tubulin. Quantification of positive
      cells were performed using Mann Whitney and Kruskal-Wallis test. RESULTS: Tissue
      analysis showed that proliferation of podocytes gradually decreased during
      development and disappeared in postnatal period. Decrease in number of ciliated
      glomerular cells and visceral podocytes (from 47% to 3%), and parietal epithelial
      cells (from 32% to 7%) characterized normal development. Nestin and nephrin co
      expressed in developing podocytes in different cellular compartments. During
      development, nephrin expression increased (from 17% to 75%) and postnatally
      changed its pattern, while nestin positive glomerular cells decreased from 98% to
      40%. CNF glomeruli displayed increased number of immature ciliated podocytes (6%)
      and parietal epithelial cells (9%). CONCLUSION: Changes in cytoplasmic alpha
      tubulin expression and reduced nephrin expression (20%) indicating association of
      incomplete podocyte maturation with failure of GFB function and appearance of
      prenatal proteinuria in CNF patients.

PMID- 30193979
TI  - Effects of undocumented immigrants exclusion from health care coverage in Spain.
AB  - BACKGROUND: In 2012 the Spanish government passed Royal Decree-Law 16/2012 (RDL)
      aimed at containing public expenditure in response to the economic crisis. This
      RDL redefined just who would be entitled to public health care. As a result, a
      large proportion of undocumented immigrants in Spain were excluded from basic
      publicly financed health care with access only being granted under particular
      circumstances (emergency care, maternal care, children under 18, asylum seekers
      and victims of human trafficking). AIM: The aims of this paper are to identify
      the specific traits of this policy, review its impact on health and health care
      access, and to evaluate its economic impact. RESULTS: Most political parties and
      health professional groups opposed the RDL, and a large number of Spanish regions
      either declined to apply it or opted to apply it partially. To date, the RDL has
      had a considerable impact on the access of undocumented immigrants to public
      health care, with evidence suggesting that approximately 870,000 people have been
      excluded. A slight increase in infectious diseases has been reported, albeit not
      as high as originally predicted, and recent evidence points to an increase in
      mortality among this population subgroup. CONCLUSIONS: Regional legislation
      favouring the coverage of undocumented immigrants might have acted as a
      counterweight and thus contained the negative health effects in this population
      subgroup. But the Constitutional Court invalidated all regional arrangements
      obliging regions to comply with the RDL.

PMID- 30193980
TI  - Migrating to electronic health record systems: A comparative study between the
      United States and the United Kingdom.
AB  - The goal of this research is to compare the healthcare information technology
      (HIT)-related policies and infrastructures of two very differently-run countries:
      The United States (US) that owns the largest private healthcare system in the
      world, and the United Kingdom (UK) that has the largest public healthcare system
      worldwide. The paper specifically focuses on the differences between the two
      countries' adoption of electronic healthcare record (EHR) systems, and their
      efforts toward interoperability, healthcare information security and privacy, and
      patient safety. Both authors on the paper are professionals in the HIT field and
      have firsthand experience designing and implementing electronic health record
      (EHR) systems. As a result, they both have a real-world grasp of HIT economics
      and the pressure of regulatory compliance. To complement their combined expertise
      and insight, the authors thoroughly reviewed the peer-reviewed and grey
      literature on healthcare policy. The paper's findings suggest that although EHR
      implementation and adoption are on the rise in the US and the UK alike, both
      countries are facing considerable hurdles in executing their vision of
      establishing their respective nationwide EHR systems. To improve patient health
      and ensure patient safety, interoperability standards that enable seamless
      communication amongst differing healthcare systems and proper security and
      privacy regulations for data collection, data handling, and data sharing are
      paramount.

PMID- 30193981
TI  - International comparison of minimum volume standards for hospitals.
AB  - INTRODUCTION: Minimum volume standards have been implemented in various countries
      for quality or safety policies. We present minimum volume standards in an
      international comparison, focusing on regulatory approaches, selected sets of
      procedures and thresholds as well as predetermined consequences of non
      compliance. MATERIALS AND METHODS: We combined a comprehensive literature search
      in electronic databases in March 2016 with a hand-search of governmental and
      related organisations' webpages. We also contacted international experts to
      verify the information we found in the literature and to obtain additional data.
      RESULTS: Minimum volume standards have been introduced in different countries
      predominantly for highly specialized surgical procedures. The same evidence has
      led to different definitions and ways of implementation of minimum volume
      standards in Germany, Canada (Ontario), the Netherlands, Switzerland, and
      Austria. The regulatory approaches to minimum volume standards and the
      predetermined consequences of non-compliance differ across the countries.
      CONCLUSION: The sets of procedures for which minimum volume standards and
      corresponding thresholds have been introduced vary across countries, possibly due
      to different regulatory approaches. In addition, key attributes of the health
      care system might affect the development and implementation of minimum volume
      standards. Therefore, it is not feasible to formulate uniform recommendations
      that are applicable to all countries. Our results provide a comprehensive
      overview of international minimum volume standards and can be used to inform
      policy decisions.

PMID- 30193982
TI  - Outpatient paediatric arthroscopy: A retrospective study in 216 Patients.
AB  - BACKGROUND: Outpatient surgery is now widely performed in adults but remains
      rarely used for paediatric orthopaedic procedures. As with adult surgery, both
      the arthroscopic equipment and anaesthesia techniques have improved over the last
      few years. Arthroscopy is particularly well advanced at the knee but can also be
      used at other joints (hip, ankle, elbow, shoulder). The primary objective of this
      study was to evaluate the feasibility of outpatient paediatric arthroscopy.
      HYPOTHESIS: Arthroscopic surgery can be performed in children on an outpatient
      basis provided an appropriate care programme is applied. MATERIALS AND METHODS:
      This single-centre retrospective study included 216 patients aged 3.8 to 18 years
      who underwent outpatient arthroscopy (knee, n=170; ankle, n=22; elbow, n=12;
      shoulder, n=6; and hip, n=6). The decision to perform the procedure on an
      outpatient basis was made with the patient during the surgeon visit then
      confirmed during the anaesthesiologist visit. The main outcome measure was
      failure of outpatient arthroscopy defined as a need for standard inpatient
      admission. The secondary outcome measures were pain or sleep disturbances on the
      day after the procedure (as assessed during a telephone call), a need to see a
      physician during the first week after the procedure, and patient satisfaction.
      RESULTS: Of the 216 patients, 9 required overnight admission (4 because of
      vomiting, 4 because of pain, and 1 because of a malaise) and 2 patients were
      admitted elsewhere for postoperative pain then discharged within 24hours. Of the
      160 patients who could be contacted on the day after the procedure, 141 (88%)
      said they had had a good night and 141 (88%) that they had little or no pain.
      Over 95% of patients were satisfied with their outpatient management. DISCUSSION:
      As with adults, arthroscopic surgery is an ideal indication for outpatient care
      in paediatric patients. Outpatient arthroscopic surgery is already widely used at
      the knee and is also suitable for other joints in the paediatric population.
      LEVEL OF EVIDENCE: IV, retrospective study.

PMID- 30193983
TI  - Cobalt-chrome and titanium alloy rods provide similar coronal and sagittal
      correction in adolescent idiopathic scoliosis.
AB  - BACKGROUND: Cobalt-chrome (CoCr) and the titanium alloy TA6V (Ti) are the
      materials most widely used for spinal instrumentations in patients with
      adolescent idiopathic scoliosis (AIS). The objective of this work was to compare
      the effectiveness of CoCr and Ti rods in terms of coronal and sagittal correction
      by pedicle screw constructs in patients with AIS. HYPOTHESIS: Correction is
      similar with CoCr and Ti rods in patients with AIS. MATERIAL AND METHOD: A
      retrospective single surgeon study was conducted in patients with AIS managed
      using pedicle screw posterior spinal fusion with high implant density and
      reduction by postero-medial translation. Follow-up was more than 2 years in all
      patients. Patients were divided into two groups based on whether the rods used
      were made of CoCr (n=30) or Ti (n=33). The groups were identical for age, Risser
      classification, follow-up duration, type of curve, and implant density. Coronal
      and sagittal parameters on standing full-spine radiographs were analysed using
      graphics software before surgery then 1 month after surgery and at last follow
      up. Quantitative data were compared by applying Student's t test. RESULTS: The
      percentage of main curve correction at last follow-up was the same in the two
      groups (76%/75%) (p=0.7). Gains in thoracic kyphosis (12 degrees /13 degrees )
      and lumbar lordosis (8 degrees /10 degrees ) were not significantly different
      between groups. At last follow-up, 3 patients had proximal junctional kyphosis, 1
      in the CoCr group and 2 in the Ti group (p=0.6). CONCLUSION: For posterior spinal
      fusion to treat AIS, with a high density of pedicle screws, correction by
      translation, and 6 mm rods, CoCr rods and Ti rods produce the same amount of
      coronal and sagittal correction. LEVEL OF EVIDENCE: IV, comparative retrospective
      study with no control group.

PMID- 30193984
TI  - C1 fracture: Analysis of consolidation and complications rates in a prospective
      multicenter series.
AB  - INTRODUCTION: Three types of C1 fracture have been described, according to
      location: type 1 (anterior or posterior arc), type 2 (Jefferson: anterior and
      posterior arc), and type 3 (lateral mass). Stability depends on transverse
      ligament integrity. The main aim of the present study was to analyze
      complications and consolidation rates according to fracture type, age and
      treatment. MATERIAL AND METHODS: The French Society of Spinal Surgery (SFCR)
      performed a multicenter prospective study on C1-C2 trauma. All patients with
      recent fracture diagnosed on CT were included. Consolidation on CT was studied at
      3 months and 1 year. Medical, neurologic, infectious and mechanical complications
      were inventoried using the KEOPS data-base. RESULTS: Sixty-three of the 417
      patients (15.1%) had C1 fracture: type 1 (33.3%), type 2 (38.1%), or type 3
      (28.6%). The transverse ligament was intact in 53.9% of cases. Treatment was non
      operative in 63.5% of cases, surgical in 27.0%, and surgical after failure of non
      operative treatment in 9.5%. There were 8 medical complications, more frequently
      in patients aged >70 years, following surgery (p<0.0001). The consolidation rate
      was 84.2% with non-operative treatment, 100% for primary surgery, and 33.3% for
      secondary surgery (p=0.002). There were 10 cases of non-union, in 4.8% of type 1,
      13.6% of type 2 and 33.3% of type 3 fractures (p=0.001). CONCLUSION: Medical
      complications showed association with age and with type of treatment. Non
      operative treatment was suited to types 1, 2 and 3 with minimal displacement and
      intact transverse ligament. C1-C2 fusion was suited to displaced unstable type 2
      fracture. Displaced type 3 fracture incurred risk of non-union. Early surgery may
      be recommended. LEVEL OF EVIDENCE: III.

PMID- 30193985
TI  - CRISPR-Cas: Complex Functional Networks and Multiple Roles beyond Adaptive
      Immunity.
AB  - CRISPR-Cas is a prokaryotic adaptive immune system that functions by
      incorporating fragments of foreign DNA into CRISPR arrays. The arrays containing
      spacers derived from foreign DNA are transcribed, and the transcripts are
      processed to generate spacer-containing mature CRISPR-RNAs that are employed as
      guides to specifically recognize and cleave the DNA or RNA of the cognate
      parasitic genetic elements. The CRISPR-Cas systems show remarkable complexity and
      diversity of molecular organization and appear to be involved in various cellular
      functions that are distinct from, even if connected to, adaptive immunity. In
      this review, we discuss some of such functional links of CRISPR-Cas systems
      including their effect on horizontal gene transfer that can be either inhibitory
      or stimulatory, connections between CRISPR-Cas and DNA repair systems as well as
      programmed cell death and signal transduction mechanisms, and potential role of
      CRISPR-Cas in transposon integration and plasmid maintenance. The interplay
      between the primary function of CRISPR-Cas as an adaptive immunity mechanism and
      these other roles defines the richness of the biological effects of these systems
      and affects their spread among bacteria and archaea.

PMID- 30193987
TI  - The lessons of Gosport for nursing education.

PMID- 30193986
TI  - Structural Plasticity of Neurexin 1alpha: Implications for its Role as Synaptic
      Organizer.
AB  - alpha-Neurexins are synaptic organizing molecules implicated in neuropsychiatric
      disorders. They bind and arrange an array of different partners in the synaptic
      cleft. The extracellular region of neurexin 1alpha (n1alpha) contains six LNS
      domains (L1-L6) interspersed by three Egf-like repeats. N1alpha must encode
      highly evolved structure-function relationships in order to fit into the narrow
      confines of the synaptic cleft, and also recruit its large, membrane-bound
      partners. Internal molecular flexibility could provide a solution; however, it is
      challenging to delineate because currently no structural methods permit high
      resolution structure determination of large, flexible, multi-domain protein
      molecules. To investigate the structural plasticity of n1alpha, in particular the
      conformation of domains that carry validated binding sites for different protein
      partners, we used a panel of structural techniques. Individual particle electron
      tomography revealed that the N-terminally and C-terminally tethered domains, L1
      and L6, have a surprisingly limited range of conformational freedom with respect
      to the linear central core containing L2 through L5. A 2.8-A crystal structure
      revealed an unexpected arrangement of the L2 and L3 domains. Small-angle X-ray
      scattering and electron tomography indicated that incorporation of the
      alternative splice insert SS6 relieves the restricted conformational freedom
      between L5 and L6, suggesting that SS6 may work as a molecular toggle. The
      architecture of n1alpha thus encodes a combination of rigid and flexibly tethered
      domains that are uniquely poised to work together to promote its organizing
      function in the synaptic cleft, and may permit allosterically regulated and/or
      concerted protein partner binding.

PMID- 30193988
TI  - The possible beneficial effects of creatine for the management of depression.
AB  - Depression, a highly prevalent neuropsychiatric disorder worldwide, causes a
      heavy burden for the society and is associated with suicide risk. The treatment
      of this disorder remains a challenge, since currently available antidepressants
      provide a slow and, often, incomplete response and cause several side effects
      that contribute to diminish the adhesion of patients to treatment. In this
      context, several nutraceuticals have been investigated regarding their possible
      beneficial effects for the management of this neuropsychiatric disorder. Creatine
      stands out as a supplement frequently used for ergogenic purpose, but it also is
      a neuroprotective compound with potential to treat or mitigate a broad range of
      central nervous systems diseases, including depression. This review presents
      preclinical and clinical evidence that creatine may exhibit antidepressant
      properties. The focus is given on the possible molecular mechanisms underlying
      its effects based on the results obtained with different animal models of
      depression. Finally, evidence obtained in animal models of depression addressing
      the possibility that creatine may produce rapid antidepressant effect, similar to
      ketamine, are also presented and discussed.

PMID- 30193989
TI  - Detrimental effects of a high-dose alcohol intoxication on sequential cognitive
      flexibility are attenuated by practice.
AB  - It is well-known that alcohol impairs behavioral control and motor response
      inhibition, but it has remained rather unclear whether it also impairs cognitive
      inhibition. As automatized behavior is less vulnerable towards the detrimental
      effects of alcohol than cognitive control processes, potential cognitive
      inhibition deficits might however improve with training. We investigated the
      effect of an acute, binge-like alcohol intoxication in a balanced within-subjects
      design, asking n=32 healthy young males to perform a backward inhibition paradigm
      once sober and once while intoxicated (~1.1 0/00). To identify the underlying
      neurophysiological mechanisms, we analyzed stimulus- and response selection
      related processes in neurophysiological data after Residue Iteration
      Decomposition (RIDE). Alcohol generally impaired behavioral task performance
      (accuracy and response times) during task switching. This was associated with
      impaired attentional processing of the task-relevant cue (reflected by reduced P1
      and N1 amplitudes), which likely resulted in a larger need for reactive control
      at the later stage of response selection and control (reflected by increased
      fronto-central theta power). Without prior practice (~30 minutes), the
      intoxicated participants further struggled to overcome the cognitive inhibition
      of a previously relevant task set (reflected by a larger backward inhibition
      effect). This was linked to reduced posterior theta power, which reflects alcohol
      induced impairments in working memory capacity and task set-relevant memory
      retrieval. As individuals with ~30 min task practice did not show the same
      alcohol-related deficit, it may be deduced that (partial) task set automatization
      via stimulus-response associations may help to reduce the detrimental effects of
      alcohol on cognitive inhibition during task switching.

PMID- 30193990
TI  - State-independent alterations of intrinsic brain network in current and remitted
      depression.
AB  - BACKGROUND: It has been proposed that state-independent, or trait,
      neurobiological alterations across illness phases may contribute to the high
      recurrence of major depressive disorder (MDD). Although intrinsic brain network
      abnormalities have been implicated consistently in MDD neuropathology, MDD state
      independent and -dependent resting-state network alterations have not been
      clearly studied. METHODS: Resting-state functional magnetic resonance imaging
      (fMRI) data were collected from 57 medication-naive first-episode current MDD
      patients, 35 remitted MDD patients, and 66 healthy controls (HCs). Independent
      component analysis (ICA) was used to extract subnetworks of the default mode
      network (DMN), central executive network (CEN), and salience network (SN).
      RESULTS: Relative to HCs, the current MDD and remitted MDD groups had decreased
      intra-intrinsic functional connectivity (iFC) in the dorsal lateral prefrontal
      cortex (dlPFC) of the left CEN, increased inter-FC between the SN and right CEN
      (rCEN), and decreased inter-FC between the anterior DMN (aDMN) and rCEN. The
      altered intra-iFC in the left CEN were correlated negatively with the depressive
      level in the remitted MDD. CONCLUSIONS: Hypoactivity of the dlPFC in the left
      CEN, increased inter-FC between the SN and rCEN, and decreased inter-FC between
      the aDMN and rCEN may reflect state-independent biomarkers of MDD.

PMID- 30193991
TI  - IMRT planning parameter optimization for spine stereotactic radiosurgery.
AB  - Spine stereotactic radiosurgery (SSRS) is a noninvasive treatment for metastatic
      spine lesions. MD Anderson Cancer Center reports a quality assurance (QA) failure
      rate approaching 15% for SSRS cases, which we hypothesized is due to difficulties
      in accurately calculating dose resulting from a large number of small-area
      segments. Clinical plans typically use 9 beams with an average of 10 segments per
      beam and minimum segment area of 2 to 3 cm2. The purpose of this study was to
      identify a set of intensity-modulated radiation therapy (IMRT) planning
      parameters that attempts to optimize the balance among QA passing rate, plan
      quality, dose calculation accuracy, and delivery time for SSRS plans. Using
      Pinnacle version 9.10, we evaluated the effects of 2 IMRT parameters: maximum
      number of segments and minimum segment area. Initial evaluation of the data
      revealed that 5 segments per beam along with minimum segment area of 4 cm2 and 4
      minimum Monitor Units (MU) per segment (544 plans) was the most promising. IMRT
      QA was performed using an OCTAVIUS 4D phantom with a 2D detector array. Our data
      showed no significant plan quality change with decreased number of segments and
      increased minimum segment area. The average coverage of GTV and CTV was 82.5 +/-
      13% (clinical) vs 82.5 +/- 13% (544) and 92.3 +/- 8% (clinical) vs 91.5 +/- 8%
      (544). Maximum point dose to cord was 11.4 +/- 3.5 Gy (clinical) vs 11.0 +/- 4.0
      Gy (544). Total plan delivery time was decreased by an average of 11.3% for the
      544 plans. In addition, the QA passing rate for the original plan vs the 544 plan
      averaged 90.3% and 91.9%, respectively. In conclusion, IMRT parameters of 5
      segments per beam and 4 cm2 minimum segment area provided a better balance of
      plan quality, delivery efficiency, and plan dose calculation accuracy for SSRS.

PMID- 30193992
TI  - Home-based training of rhythmic skills with a serious game in Parkinson's
      disease: Usability and acceptability.
AB  - OBJECTIVES: To evaluate the adherence, usability and acceptance of a
      rehabilitation protocol with a music-based serious game (SG) and its effect on
      rhythmic skills in Parkinson disease (PD). METHODS: Sixteen PD patients with mild
      cognitive and motor impairments were included (mean [SD] age 65 [7.28] years and
      Hoehn & Yahr score 2-3). Rehabilitation consisted of a 6-week at-home training
      program targeting rhythmic skills with a dedicated SG, Rhythm Workers,
      implemented on a tablet device. Patients were asked to play the game at least
      30min, 3 times a week. Two half-day evaluations were conducted before and after
      rehabilitation. Time played and average game scores were recorded. Suitability
      was evaluated by a questionnaire inspired by the Suitability Evaluation
      Questionnaire (SEQ) and rhythmic skills by the Beat Alignment Test from the
      Battery for the Assessment of Auditory Sensorimotor and Timing Abilities
      (BAASTA). RESULTS: Patients played a mean (SD) of 313 (243) min, namely 57.9% of
      the expected time; the mean game score was 48.8/100 (19.5). The mean SEQ score
      for 12 patients was 29.2/45 (8.2); suitability was good to excellent for 10
      patients. Beat perception reflecting rhythmic skills improved significantly in
      all but 5 patients. CONCLUSION: This study showed good to excellent suitability
      of an SG used on a tablet interface for rhythmic training in PD and the
      feasibility of this type of training in this population.

PMID- 30193993
TI  - Indicators of long-term return to work after severe traumatic brain injury: A
      cohort study.
AB  - BACKGROUND: Return to work (RTW) is a major objective in the rehabilitation of
      individuals with severe traumatic brain injury (TBI). Implications for long-term
      occupational integration (beyond 5 years) have rarely been studied. OBJECTIVE:
      The objective was to assess long-term RTW and the associated factors after severe
      TBI. MATERIAL AND METHODS: Retrospective analysis of a cohort of individuals 16
      to 60 years old admitted to hospital after severe TBI from 2005 to 2009 and
      followed prospectively. Medical and occupational data were collected from medical
      files and by systematic telephone interview to assess outcome at a minimum of 6
      years post-trauma. Factors associated with RTW were investigated by multivariable
      regression analysis, estimating prevalence ratios (PRs) and 95% confidence
      intervals (CIs). A proportional hazards model was used to study RTW delay,
      estimating hazard ratios (HRs). RESULTS: Among the 91 individuals included (mean
      [SD] age 28.5 [11.3] years; 79% male), 63.7% returned to work after a mean of
      about 20 months, and 57.1% were still working at the time of the survey. Factors
      significantly associated with RTW on multivariable analysis were higher
      educational level (adjusted PR, 1.53; 95% CI, 1.15 to 2.03), absence of motor
      disability (adjusted PR, 1.82; 1.12 to 2.95) and behavioural disorder (adjusted
      PR, 1.26; 1.01 to 1.60), as well as disabled worker status (adjusted PR, 1.26;
      1.01 to 1.60) (likelihood of the multivariate analysis model 53.1). Delayed RTW
      was associated with health insurance payments (adjusted HR, 0.40; 95% CI, 0.22 to
      0.71), motor disability (adjusted HR, 0.34; 0.15 to 0.76), low educational level
      (adjusted HR, 2.20; 1.06 to 4.56) and moderate disability on the Extended Glasgow
      Outcome Scale (adjusted HR, 0.49; 0.27 to 0.91) (likelihood of the multivariate
      analysis model 335.5). CONCLUSION: Individuals with the most severe TBI are able
      to RTW and remain in work. This study highlights the multiple determinants
      involved in RTW and the role of socioenvironmental factors.

PMID- 30193994
TI  - Epithelial-to-mesenchymal transition-based morphogenesis of dorsal mesentery and
      gonad.
AB  - Dorsal mesentery and gonad (ovary and testis) are formed in distinct regions of
      the body and have different characteristics. Recent studies using chicken embryos
      showed that progenitors of these two organs are derived from the coelomic lining
      region, a ventral part of the medial lateral plate mesoderm (M-LPM). Furthermore,
      both types of progenitors develop in a similar manner, concomitant with
      morphological changes termed the epithelial-to-mesenchymal transition (EMT). EMT
      processes in both dorsal mesentery and gonad formation are regulated by BMP
      signaling. Interestingly, EMT-based morphogenetic events occur repetitively at M
      LPM specification before dorsal mesenteric and gonadal formation, at ovary
      formation later in embryogenesis, and even during adult ovary repair. We review
      recent findings related to EMT-based morphogenesis and the governing molecular
      mechanisms, mainly in early dorsal mesenteric and gonadal formation, as well as
      in their anlages and derivatives.

PMID- 30193995
TI  - The mesentery as the epicenter for intestinal regeneration.
AB  - The mesentery, a newly minted organ, plays various anatomical and physiological
      roles during animal development. In echinoderms, and particularly in members of
      the class Holothuroidea (sea cucumbers) the mesentery plays an additional unique
      role: it is crucial for the process of intestinal regeneration. In these
      organisms, a complete intestine can form from cells that originate in the
      mesentery. In this review, we focus on what is known about the changes that take
      place in the mesentery and what has been documented on the cellular and molecular
      mechanisms involved. We describe how the events that unfold in the mesentery
      result in the formation of a new intestine.

PMID- 30193996
TI  - The contributions of mesoderm-derived cells in liver development.
AB  - The liver is an indispensable organ for metabolism and drug detoxification. The
      liver consists of endoderm-derived hepatobiliary lineages and various mesoderm
      derived cells, and interacts with the surrounding tissues and organs through the
      ventral mesentery. Liver development, from hepatic specification to liver
      maturation, requires close interactions with mesoderm-derived cells, such as
      mesothelial cells, hepatic stellate cells, mesenchymal cells, liver sinusoidal
      endothelial cells and hematopoietic cells. These cells affect liver development
      through precise signaling events and even direct physical contact. Through the
      use of new techniques, emerging studies have recently led to a deeper
      understanding of liver development and its related mechanisms, especially the
      roles of mesodermal cells in liver development. Based on these developments, the
      current protocols for in vitro hepatocyte-like cell induction and liver-like
      tissue construction have been optimized and are of great importance for the
      treatment of liver diseases. Here, we review the roles of mesoderm-derived cells
      in the processes of liver development, hepatocyte-like cell induction and liver
      like tissue construction.

PMID- 30193997
TI  - Synergistic Reduction of Apoptosis With Diazoxide and Erythropoietin in Spinal
      Cord Ischemic Injury.
AB  - BACKGROUND: Paraplegia remains a devastating complication of thoracoabdominal
      aortic intervention. Metabolic stress induces expression of beta common receptor
      subunit of erythropoietin (EPO) receptor (betacR) to exert a neuroprotective
      effect in spinal cord ischemia reperfusion injury (SCIR). Diazoxide (DZ) has been
      shown to induce ischemic tolerance. We previously reported that DZ upregulated
      betacR expression and enhanced the neuroprotective effects of EPO through the
      upregulation of betacR. We hypothesize that betacR expression induced by DZ
      before ischemia amplifies the antiapoptotic effects of EPO in a murine model of
      SCIR. METHODS: Experimental groups included phosphate-buffered saline (PBS)
      pretreatment + PBS immediately before the operation, PBS+EPO, DZ+PBS, DZ+EPO, and
      sham. Spinal cord ischemia was induced by a 4-minute thoracic aortic cross-clamp.
      Functional scoring (Basso Mouse Score) was done at 12-hour intervals for 48
      hours. Spinal cords were harvested for histologic analysis, and antiapoptotic
      factors (caspase 3, 8, and 9, B-cell lymphoma-2, and neuroglobin) were evaluated
      by Western blot analysis. RESULTS: The motor function of DZ+EPO group was
      significantly preserved compared with all other groups. The levels of cleaved
      caspase 8 and 3 in DZ+EPO were significantly lower than in the other groups. Mice
      treated with DZ+EPO had significantly fewer terminal deoxynucleotide transferase
      mediated deoxy uridine triphosphate nick-end labeling-positive cells than other
      groups. CONCLUSIONS: Optimized upregulation of betacR by DZ can increase the
      extrinsic antiapoptotic effects of EPO. Better understanding of this synergetic
      mechanism may serve to help prevent ischemic complications caused by aortic
      intervention.

PMID- 30193998
TI  - Paradoxical Neochords to Treat Systolic Anterior Motion in Hypertrophic
      Obstructive Cardiomyopathy.
AB  - We describe an approach to address the left ventricular outflow tract obstruction
      (LVOTO) in Hypertrophic Obstructive Cardiomyopathy (HOCM) with concomitant
      systolic anterior motion of mitral valve. This approach has two main purposes: to
      enlarge the LVOT through a "moderate" myectomy and to "discipline" the excessive
      movement of the mitral valve anterior leaflet through paradoxical chords
      implantation(2,3) and, similarly, the papillary muscle too, if necessary, hanging
      paradoxical chords between the papillary muscle itself and the posterior mitral
      annulus(5).

PMID- 30193999
TI  - Thoracic Bleeding Complications in Patients With Venovenous Extracorporeal
      Membrane Oxygenation.
AB  - BACKGROUND: Patients with respiratory failure are treated more frequently with
      venovenous extracorporeal membrane oxygenation (vv-ECMO). These patients are at
      risk for bleeding due to complex multifactorial coagulation disorders resulting
      from the extracorporeal circulation. METHODS: A retrospective analysis was
      conducted of prospectively collected data on all patients requiring vv-ECMO
      between December 2010 and December 2016. End points were the incidence,
      consequence, and in-hospital mortality of patients with thoracic bleeding
      complications. RESULTS: The study included 418 patients (aged 50 +/- 16.5 years)
      requiring vv-ECMO. In 23.2% (n = 97) of patients, relevant hemorrhage was
      documented. Thoracic bleeding developed in 40 patients (41.2%), followed by
      diffuse (21.6%), cerebral (14.4%), gastrointestinal (6.2%), cannulation site
      (6.2%), and other bleeding locations. Thoracic bleeding complications occurred
      spontaneously (40%), postoperatively (37.5%), after interventions (20%), and
      after trauma (2.5%). A thoracic operation was performed in 60% (n = 24) of these
      patients, and a repeated operation due to bleeding was necessary in 45.8%. Mean
      ECMO duration (18.6 +/- 16.8 days; p = 0.035) and hospital length of stay (58 +/-
      50 days; p = 0.002) were significantly longer than that in patients without
      bleeding. In-hospital mortality was significantly higher in patients with
      thoracic bleeding complications (52.5%) than in patients without bleeding
      complications (32.7%; p = 0.013). CONCLUSIONS: Thoracic bleeding complications
      were observed in 9.6% of patients and represented the most frequent bleeding
      complication during vv-ECMO treatment. Almost 60% of patients required surgical
      revision, and nearly half of these patients underwent a repeated operation.
      Because mortality is high in these patients, vv-ECMO should be performed in only
      centers experienced with thoracic surgery.

PMID- 30194000
TI  - Nuanced Approach to Surgical Tricuspid Valve Endocarditis.

PMID- 30194001
TI  - Motion at the Sternal Edges During Upper Limb and Trunk Tasks In-Vivo as Measured
      by Real-Time Ultrasound Following Cardiac Surgery: A Three-Month Prospective,
      Observational Study.
AB  - BACKGROUND: Despite a paucity of evidence, patients following cardiac surgery via
      median sternotomy are routinely prescribed sternal precautions that restrict
      upper limb and trunk movements, with the rationale of reducing postoperative
      sternal complications such as sternal wound dehiscence, instability, infection
      and/or pain. The primary aim of this study was to measure motion at the sternal
      edges during dynamic upper limb and trunk tasks to better inform future sternal
      precautions and optimise postoperative recovery. Motion at the sternal edges was
      measured using ultrasound, which has been demonstrated to be a clinically valid
      and reliable measure in patients following cardiac surgery. METHODS: Seventy-five
      patients following cardiac surgery via median sternotomy with conventional
      stainless steel wire closure were recruited. Motion at the sternal edges in the
      lateral (coronal plane) and anterior-posterior (sagittal plane) directions was
      measured at the level of the fourth intercostal space (mid-sternum) using
      ultrasound. Ultrasound measures were taken at rest and during five dynamic upper
      limb and trunk tasks (deep inspiration, cough, unilateral and bilateral upper
      limb elevation and sit to stand), over the first 3 postoperative months (3 to 7
      days, 6 weeks and 3 months postoperatively). Sternal pain, functional status and
      sternal healing were also observed over the same postoperative period. RESULTS:
      The magnitude of overlap of the sternal edges in the lateral direction, and
      separation of the sternal edges in the anterior-posterior direction, both
      significantly decreased by 0.01cm, over the first 3 postoperative months
      (p<0.01). Coughing, however, produced a significant increase in separation of the
      sternal edges in the lateral direction (0.01-0.02cm) and pain (12-63%), compared
      to rest and all other tasks, at each postoperative time point (p<0.01).
      Additionally, there was a significant decrease in sternal pain (81%) and increase
      in postoperative function (79%) over the same postoperative period (p<0.01). At 3
      months postoperatively, five (7%) participants demonstrated radiological sternal
      union and one (1%) participant was diagnosed with clinical sternal instability.
      CONCLUSIONS: A small magnitude of multi-planar motion at the sternal edges, at
      the mid-sternum, was demonstrated during dynamic upper limb and trunk tasks in a
      cohort of cardiac surgery patients post-sternotomy, over the first 3
      postoperative months. Future research investigating motion at different levels of
      the sternum, with varying methods of sternal closure, and over a longer
      postoperative period is warranted to better inform sternal precautions and
      optimise postoperative recovery.

PMID- 30194002
TI  - Uptake and safety of Hepatitis B vaccination during pregnancy: A Vaccine Safety
      Datalink study.
AB  - INTRODUCTION: Hepatitis B virus (HBV) infection acquired during pregnancy can
      pose a risk to the infant at birth that can lead to significant and lifelong
      morbidity. Hepatitis B vaccine (HepB) is recommended for anyone at increased risk
      for contracting HBV infection, including pregnant women. Limited data are
      available on the safety of HepB administration during pregnancy. OBJECTIVES: To
      assess the frequency of maternal HepB receipt among pregnant women and evaluate
      the potential association between maternal vaccination and pre-specified maternal
      and infant safety outcomes. METHODS: We examined a retrospective cohort of
      pregnancies in the Vaccine Safety Datalink (VSD) resulting in live birth outcomes
      from 2004 through 2015. Eligible pregnancies in women aged 12-55 years who were
      continuously enrolled from 6 months pre-pregnancy to 6 weeks postpartum in VSD
      integrated health systems were included. We compared pregnancies with HepB
      exposure to those with other vaccine exposures, and to those with no vaccine
      exposures. High-risk conditions for contracting HBV infection were identified up
      to one-year prior to or during the pregnancy using ICD-9 codes. Maternal and
      fetal adverse events were also evaluated according to maternal HepB exposure
      status. RESULTS: Among over 650,000 pregnancies in the study period, HepB was
      administered at a rate of 2.1 per 1000 pregnancies (n = 1399), commonly within
      the first 5 weeks of pregnancy. Less than 3% of the HepB-exposed group had a high
      risk ICD-9 code indicating need for HepB; this was similar to the rate among HepB
      unvaccinated groups. There were no significant associations between HepB exposure
      during pregnancy and gestational hypertension, gestational diabetes, pre
      eclampsia/eclampsia, cesarean delivery, pre-term delivery, low birthweight or
      small for gestational age infants. CONCLUSIONS: Most women who received maternal
      HepB did not have high-risk indications for vaccination. No increased risk for
      the adverse events that were examined were observed among women who received
      maternal HepB or their offspring.

PMID- 30194003
TI  - Effect of the introduction of pneumococcal conjugate vaccines on serotype
      prevalence in Kuwait and Saudi Arabia.
AB  - BACKGROUND: Streptococcus pneumoniae infection is a major cause of morbidity and
      mortality. Although pneumococcal disease burden in Kuwait and Saudi Arabia is
      considered high, comprehensive surveillance data on pneumococcal conjugate
      vaccine (PCV) effects are lacking. METHODS: Sterile isolates from patients in
      Kuwait (2003-2016) and Saudi Arabia (aged <=5 years, 2000-2010; all patients,
      2011-2015) were included. Serotyped isolates were classified by inclusion in the
      7-valent (PCV7) or 13-valent PCV (PCV13); isolates of other serotypes were
      classified as "non-PCV13". Isolate frequency (number of isolates/year) and
      classification of isolates according to vaccine type were assessed by period
      (before PCV, after PCV7, and after PCV13 introduction). RESULTS: In Kuwait, the
      frequency of collected isolates was highest after PCV7 introduction. Decreased
      frequency of PCV7 serotypes was seen after PCV13 introduction compared with
      before PCV and after PCV7 introduction. Increased frequency of the 6 additional
      serotypes in PCV13 and non-PCV13 serotypes was observed after PCV7 introduction
      with a subsequent decrease in the 6 additional serotypes in PCV13 and non-PCV13
      serotypes after PCV13 introduction. The percentage of isolates of vaccine
      serotypes in Kuwait decreased over time. In Saudi Arabia, the frequency of
      collected isolates was highest after PCV7 introduction. An increased frequency of
      PCV7 serotypes was observed after PCV7 introduction, with a further decrease
      after PCV13 introduction. For the 6 additional serotypes in PCV13, an increased
      frequency was seen after PCV7 and PCV13 introduction compared to before PCV
      introduction. For non-PCV13 serotypes, an increased frequency was observed after
      PCV13 introduction compared to after PCV7 introduction. The percentage of
      isolates covered by PCV13 serotypes was similar across periods, while a
      substantial decrease in isolates covered by PCV7 was seen after PCV13
      introduction. CONCLUSION: PCVs in Kuwait and Saudi Arabia resulted in decreased
      frequency of some vaccine serotypes and an emergence of some non-PCV13 serotypes.
      Further investigation is warranted.

PMID- 30194004
TI  - Reference antigen-free and antibody-free LTD-IDMS assay for influenza H7N9
      vaccine in vitro potency determination.
AB  - Influenza vaccines are the most effective intervention to prevent the substantial
      public health burden of seasonal and pandemic influenza. Hemagglutinin (HA), as
      the main antigen in inactivated influenza vaccines (IIVs), elicits functional
      neutralizing antibodies and largely determines IIV effectiveness. HA potency has
      been evaluated by single-radial immunodiffusion (SRID), the standard in vitro
      potency assay for IIVs, to predict vaccine immunogenicity with a correlation to
      protective efficacy. We previously reported that limited trypsin digestion (LTD)
      selectively degraded stressed HA, so that an otherwise conformationally
      insensitive biophysical quantification technique could specifically quantify
      trypsin-resistant, immunologically active HA. Here, we demonstrate that isotope
      dilution mass spectrometry (IDMS), a method capable of quantifying the absolute
      HA concentration without reference antigen use, can be further expanded by adding
      LTD followed with precipitation to selectively quantify the active HA. We test
      the LTD-IDMS assay on H7N9 vaccines stressed by low pH, raised temperature, or
      freeze/thaw cycles. This method, unlike SRID, has no requirement for strain
      specific reference antigens or antibodies and can generate potency values that
      correlate with SRID. Thus, LTD-IDMS is a promising alternative in vitro potency
      assay for influenza vaccines to complement and potentially replace SRID in a
      pandemic when strain specific reagents may not be readily available.

PMID- 30194006
TI  - Five-year overall survival following chemoradiation among HIV-positive and HIV
      negative patients with locally advanced cervical carcinoma in a South African
      cohort.
AB  - OBJECTIVES: In South Africa, where HIV prevalence among adults is 18.9%, cervical
      carcinoma is the second most common malignancy in women. However, oncology
      services are considerably more accessible in South Africa than in many
      neighbouring countries. This study reports five-year overall survival in a cohort
      of HIV-positive and -negative cervix carcinoma patients undergoing primary
      radiotherapy at a single institution in South Africa. METHODS: Prospective cohort
      study of all locally advanced cervix carcinoma patients referred for radiotherapy
      (EBRT) from July 2007 to November 2011. Overall survival (OS) was the primary end
      point. RESULTS: A total of 492 patients commenced treatment with radical intent,
      including 71 HIV-positive patients (14.4%) and 421 HIV-negative patients (85.6%).
      Of the 433 who were prescribed standard fractionation EBRT, 384 were prescribed
      concurrent platinum-based chemotherapy (88.7%). Fewer HIV-positive than HIV
      negative patients (58.5% vs. 76.1%; p = 0.007) completed >=4 cycles. The OS of
      HIV-negative patients was 49.5% (95%CI; 44.6%-54.4%) at 5 years. The OS of HIV
      positive patients was significantly lower, 35.9% (95% CI; 23.9%-48.0%) at 5 years
      (p = 0.002). In our Cox models, factors affecting outcome were HIV infection,
      stage IIIB disease, presence of hydronephrosis, and delivery of concurrent
      chemotherapy. CONCLUSION: In our large cohort, HIV-positive patients had poorer
      survival than HIV-negative patients, however nearly 40% survived 5 years,
      justifying provision of the best standard of care to HIV-positive patients with
      cervical carcinoma.

PMID- 30194005
TI  - Assessing inter-component heterogeneity of biphasic uterine carcinosarcomas.
AB  - OBJECTIVE: Uterine carcinosarcoma (UCS) is a rare and aggressive form of uterine
      cancer. It is bi-phasic, exhibiting histological features of both malignant
      epithelial (carcinoma) and mesenchymal (sarcoma) elements, reflected in ambiguity
      in accepted treatment guidelines. We sought to study the genomic and
      transcriptomic profiles of these elements individually to gain further insights
      into the development of these tumors. METHODS: We macro-dissected carcinomatous,
      sarcomatous, and normal tissues from formalin fixed paraffin embedded uterine
      samples of 10 UCS patients. Single nucleotide polymorphism microarrays, targeted
      DNA sequencing and whole-transcriptome RNA-sequencing were performed. Somatic
      chromosomal alterations (SCAs), point mutation and gene expression profiles were
      compared between carcinomatous and sarcomatous components. RESULTS: In addition
      to TP53, other recurrently mutated genes harboring putative driver or loss-of
      function mutations included PTEN, FBXW7, FGFR2, KRAS, PIK3CA and CTNNB1, genes
      known to be involved in UCS. Intra-patient somatic mutation and SCA profiles were
      highly similar between paired carcinoma and sarcoma samples. An epithelial
      mesenchymal transition (EMT) signature tended to differentiate components, with
      EMT-like status more common in advanced-stage patients exhibiting higher inter
      component SCA heterogeneity. CONCLUSIONS: From DNA analysis, our results indicate
      a monoclonal disease origin for this cohort. Yet expression-derived EMT statuses
      of the carcinomatous and sarcomatous components were often discrepant, and
      advanced cases displayed greater genomic heterogeneity. Therefore, separately
      profiled components of UCS tumors may better inform disease progression or
      potential.

PMID- 30194008
TI  - Synthesis and biological evaluation of isoxazolyl-sulfonamides: A non-cytotoxic
      scaffold active against Trypanosoma cruzi, Leishmania amazonensis and Herpes
      Simplex Virus.
AB  - In this study we report the synthesis, characterization, biological evaluation,
      and druglikeness assessment of a series of 20 novel isoxazolyl-sulfonamides,
      obtained by a four-step synthetic route. The compounds had their activity against
      Trypanosoma cruzi, Leishmania amazonensis, Herpes Simplex Virus type 1 and
      cytotoxicity evaluated in phenotypic assays. All compounds have drug-like
      properties, showed low cytotoxicity and were promising regarding all other
      biological activities reported herein, especially the inhibitory activity against
      T. cruzi. The compounds 8 and 16 showed significant potency and selectivity
      against T. cruzi (GI50 = 14.3 uM, SI > 34.8 and GI50 = 11.6 uM, SI = 29.1,
      respectively). These values, close to the values of the reference drug
      benznidazole (GI50 = 10.2 uM), suggest that compounds 8 and 16 represent
      promising candidates for further pre-clinical development targeting Chagas
      disease.

PMID- 30194007
TI  - Nucleotide excision repair protein ERCC1 and tumour-infiltrating lymphocytes are
      potential biomarkers of neoadjuvant platinum resistance in high grade serous
      ovarian cancer.
AB  - OBJECTIVE: ERCC1 is a nucleotide excision repair protein that may have a role in
      drug resistance in high grade serous ovarian cancer (HGSOC). We hypothesized that
      ERCC1 expression and tumour infiltrating lymphocytes (TILS) are induced by
      chemotherapy in HGSOC, which may be prognostically useful. METHODS: 115 HGSOC
      patients were used for this study. 92 (80%) of the tissue analysed had not been
      exposed to platinum chemotherapy. The remaining 20% (n = 23) of cases received
      combination or monotherapy with carboplatin before tissue was collected.
      Immunohistochemistry was used to score for ERCC1 expression and morphology to
      score for TILs. Correlation analysis of all clinical parameters, TILs and ERCC1
      and Kaplan-Meier survival analysis was performed using the ERCC1 and TILs scoring
      parameters (0, 1, 2 or 3). RESULTS: ERCC1 expression was 2-fold higher in the
      neoadjuvant chemotherapy group compared to the primary cytoreductive surgery
      group (p < 0.0001). The mean overall survival for the neoadjuvant group with high
      ERCC1 was 141.6 +/- 20.2 months which was significantly longer than absent ERCC1
      survival of 61 + 22.6 months (p = 0.028). ERCC1 score strongly correlated with
      TILs score across the whole cohort (0.349, p = 1.3 * 10-4) suggesting there is a
      relationship between ERCC1 expression and TILs, but this requires further
      investigation. CONCLUSION: In conclusion, ERCC1 was identified as a potential
      biomarker of platinum response overall survival in HGSOC undergoing neoadjuvant
      HGSOC treatment.

PMID- 30194009
TI  - Carotid intima-media thickness and plagues are associated with indicators of
      peripheral artery diseases in patients with diabetes.
AB  - AIMS: We investigated associations of carotid intima-media thickness (CIMT) and
      carotid plaque with ankle-brachial index (ABI) and toe-brachial index (TBI) in
      Chinese adults. METHODS: A cross-sectional analysis was performed in 6688
      participants from a well-defined Chinese community. CIMT and carotid plaque was
      measured with a high-resolution B-mode tomographic ultrasound system. Low ABI was
      defined as ABI <= 0.90. Low TBI was defined as TBI <= 0.60. Carotid plaques were
      classified as normal, homogeneous or heterogeneous according to morphology.
      RESULTS: After adjusting for age, sex and body mass index, each 0.10 mm CIMT
      increase was associated with 0.0123 unit decrease in TBI (P = 0.004) and 0.0063
      in ABI (P = 0.04) in patients with diabetes. After further adjustments for waist
      circumference, smoking and drinking habits, hypertension, lipids and hemoglobin
      A1c, the associations between CIMT and TBI remained significant; while those with
      ABI were disappeared. Meanwhile, each 0.10 mm increment of CIMT or rank of
      carotid plaque morphology was associated with a risk of presence of low TBI
      (CIMT: odds ratio: 1.21, 95% confidence interval: 1.05-1.40; carotid plaque
      morphology: 1.45, 1.01-2.08) in patients with diabetes after adjustments.
      However, no associations were found between CIMT or carotid plaque morphology and
      TBI or ABI in non-diabetic participants. CONCLUSIONS: CIMT and carotid plaque
      morphology were significantly associated with TBI in patients with diabetes.

PMID- 30194010
TI  - Novel drug delivery systems for natural extracts: The case study of Vitis
      Vinifera extract-SiO2 nanocomposites.
AB  - Ball Milling technique has been used to prepare for the first time Vitis Vinifera
      extract-silica nanocomposites (VV-SiO2 NCs), which combine the pharmacological
      effects of the extract with the effectiveness of silica as drug delivery system
      and active component in the treatment of wound healing. Different contents (1.0,
      9.0 and 33.0 wt%) of Vitis Vinifera ethanolic extract were loaded into the silica
      matrix by grinding the extract with fumed silica using a planetary mill
      apparatus. The effect of the starting mixture composition and milling time on the
      final products was examined. The efficiency of the milling process was studied by
      X-ray Powder Diffraction, Nuclear Magnetic Resonance, and Infrared Spectroscopy,
      indicating that the natural extract was not affected by the increasing of the
      milling time. The successful loading of the extract was demonstrated by Nitrogen
      adsorption/desorption measurements, which showed a decrease in the SSA and pore
      volume of the silica with the increasing of the extract amount. Morphology of the
      nanocomposites, investigated by Scanning Electron Microscopy, showed an increased
      agglomeration in the nanocomposites with the increment of the VV extract amount.
      Studies on the total phenol quantification and antioxidant activity of the
      natural extract before and after incorporation in the silica matrix were also
      carried out. The obtained results indicate that the milling process does not
      alter the VV extract components, which result to be embedded in the silica
      matrix. An increase of the antioxidant activity with the increment of the extract
      amount in the nanocomposites, up to values comparable to the pure VV extract, was
      also observed.

PMID- 30194011
TI  - Development of a skin-friendly microemulsion for dermal allergen-specific
      immunotherapy.
AB  - Due to their role in immune responses, the skin dendritic cells (i.e. epidermal
      Langerhans cells and dermal dendritic cells) have become of great interest to
      researchers in the past decades. A dermal administration of allergens could
      target these professional antigen-presenting cells directly and build up
      immunotolerance. Additionally, many of the adverse side effects, which are seen
      in the current state of the art specific immunotherapy routes, could be avoided.
      Therefore, in this study a penetration enhancing microemulsion was developed and
      its physicochemical properties were determined under several storage conditions.
      The influence of different preservatives on the microemulsion stability was
      observed. We examined epidermal penetration of Alexa Fluor-647 labelled bee-venom
      phospholipase A2 (Api m 1) using the Franz diffusion cell set up and confocal
      laser-scanning microscopy. First results of an in-vivo Api m 1-allergic mouse
      model indicated the protective efficacy of dermal AIT with our newly developed
      microemulsion. Summarily, the developed microemulsion is a suitable, stable drug
      delivery system for the topical administration of proteogenic allergens into the
      epidermis and is able to reach dendritic cells in the skin.

PMID- 30194012
TI  - In vivo evaluation of chitosan based local delivery systems for atorvastatin in
      treatment of periodontitis.
AB  - Periodontitis is a local inflammatory disease initiated by bacteria accumulation
      and results in cytokine mediated alveolar bone resorption and tissue destruction.
      In this study, the effect of locally delivered atorvastatin (2% w/v) containing
      chitosan formulations in the treatment of periodontitis was evaluated in rats
      with ligature induced periodontitis. The levels of interleukin-1beta (IL-1beta),
      IL-6, IL-8, IL-10, transforming growth factor-beta1 (TGF-beta1), TGF-beta2 and
      TGF-beta3 were measured after treatment with formulations. Histomorphometric
      analysis included the measurements of the area of alveolar bone and the distance
      between cemento-enamel junction (CEJ) and connective tissue attachment to tooth.
      Inflammatory and osteoclastic activity scores were given semiquantitatively.
      Following the administration of atorvastatin, release of pro-inflammatory (IL
      1beta, IL-6 and IL-8) and anti-inflammatory (TGF-beta1 and TGF-beta2) cytokines
      was found to decrease, with a significant alveolar bone healing, when compared to
      that of control. The anti-inflammatory effect was observed to enhance in presence
      of chitosan. These findings suggest that chitosan based delivery system for a
      statin group drug, atorvastatin is a promising for the treatment of periodontal
      disease.

PMID- 30194013
TI  - A novel test system for the evaluation of oral mucoadhesion of fast
      disintegrating tablets.
AB  - Oromucosal drug delivery is necessary when a local effect in the oral cavity is
      required. Bioadhesive formulations should be advantageous because a larger
      fraction of the active principal is retained at the site of action allowing for
      an enhanced and prolonged effect. Despite a variety of mucoadhesion test systems
      being described in literature, none of these in-vitro tests does relate to
      physiological conditions in the oral cavity and suites for the testing of
      complete dosage forms, e.g. tablets. The novel mucoadhesion test is based on
      porcine buccal mucosa. Constituents, osmolality and pH of the used artificial
      saliva was as close as possible to physiologic conditions and the flushing rate
      was equivalent to the physiological secretion rate of saliva. Suitability of the
      novel test was evaluated with ODTs with live probiotic bacteria as the active
      principle. With the novel test system, it was shown that in the presence of
      mucoadhesive polymers (Carbopol(r), Metolose(r) and chitosan) up to 36 % of the
      probiotic bacteria adhered to the mucosa corresponding to a two- or threefold
      increase compared to tablets without such polymers. Furthermore, the influence of
      the tablet size (contact area) on the mucoadhesive properties could be resolved.

PMID- 30194014
TI  - Nrf2 deletion results in impaired performance in memory tasks and hyperactivity
      in mature and aged mice.
AB  - Oxidative stress has been implicated in both the functional and cognitive decline
      associated with neuropsychiatric diseases and aging. A master regulator of the
      body's defense mechanism against oxidative stress is nuclear factor erythroid 2
      related factor (NRF2). Here we investigated the effects of NRF2 deletion on motor
      and cognitive performance in "Aged" mice (17-25 months old) as compared to
      "Mature" mice (3-15 months old). We observed that the Aged Nrf2-/- mice were
      hyperactive and exhibited impaired acquisition of an active avoidance response.
      Furthermore, the Mature mice also displayed a hyperactive phenotype and had
      impaired working memory in the probe trial of the water radial arm maze. Overall,
      it appears that NRF2 may be implicated in memory and activity functions and its
      deletion exacerbates deficits associated with aging. These observations provide a
      model for assessing the role of oxidative stress in age-related disorders.

PMID- 30194015
TI  - Diverse facets of cortical interneuron migration regulation - Implications of
      neuronal activity and epigenetics.
AB  - The proper function of the cerebral cortex relies on the delicate balance of
      excitation and inhibition determined by the accurate number and subtype
      composition of the diverse group of inhibitory gamma-aminobutyric (GABA)
      expressing interneurons. Developmental defects can lead to impaired cortical
      inhibition and seem implicated in neuropsychiatric disorders like schizophrenia.
      The multifaceted development of cortical interneurons, of which the long-range
      migration from the basal telencephalon to cortical targets represents a critical
      step, is orchestrated by various intrinsic and extrinsic factors. Besides
      motogenic factors, neuronal activity determined by neurotransmitter and calcium
      signaling turned out as a crucial driver of cortical interneuron motility and
      migration, whereas the directionality is orchestrated by specific guidance
      receptors. Thereby, the responses towards different guidance and
      neurotransmitters cues appear highly stage and cell type- specific, relying on a
      complex transcriptional network that instruct the expression of particular
      receptor combinations. The contribution of epigenetic mechanisms to gene
      expression control that direct cortical interneuron migration and maturation are
      now beginning to be approached. This is key to decipher interneuron subtype
      specific developmental programs and helps to understand how environmental signals
      can shape subtype-specific maturation. This review provides an overview about the
      achievements that were made in uncovering the regulatory networks orchestrating
      the migration of distinct cortical interneuron subtypes with focus on the role
      neuronal activity and epigenetic transcriptional control.

PMID- 30194016
TI  - Neurophysiological effects of mirror visual feedback in stroke patients with
      unilateral hemispheric damage.
AB  - BACKGROUND AND OBJECTIVE: Mirror visual feedback (MVF; the illusory perception of
      movement in one hand upon viewing the moving opposite hand in a midsagittal
      mirror) is thought to facilitate restoration of mal-adaptive neurophysiological
      processes underlying conditions like complex regional pain syndrome and phantom
      limb pain, and to have a positive effect on brain plasticity processes underlying
      motor recovery after stroke. However, its exact mode of action remains unclear.
      The aim of the current study was to explore the immediate neurophysiological
      effects of MVF in patients with stroke-related hemiparesis. We also investigated
      how these effects relate to lesion location and extent. METHOD: EEG and EMG data
      were obtained from 14 first-event sub-acute stroke patients (8 with right-, 6
      with left-hemiparesis) during repeated wrist extension movements of the Non
      paretic Upper-Limb (NUL), without (NUL/M-) and with (NUL/M+) a midsagittal
      mirror, as well as during bilateral movements with a mirror (Bil/M+). EEG data
      was correlated with normalized lesion data obtained from follow-up CT scans.
      RESULTS: NUL movement was accompanied by an asymmetric event-related de
      synchronization (ERD) of low-beta EEG oscillations, with a more conspicuous ERD
      in the non-affected hemisphere. In the mirror condition, ERD magnitude was
      attenuated in both hemispheres. Stronger attenuation in the non-affected
      hemisphere abolished the hemispheric asymmetry. ERD attenuation by the mirror was
      affected by lesion side, the severity of hemiparesis and by lesion location and
      extent. CONCLUSION: Following hemispheric stroke, the magnitude of low-beta ERD
      accompanying unilateral movement of the non-involved upper limb, and its
      hemispheric asymmetry, are both reduced by MVF. Low-beta ERD dynamics may serve
      as a marker of neurophysiological response to MVF in research aimed to elucidate
      the factors influencing patients' clinical gain from this treatment.

PMID- 30194017
TI  - The effect of transcranial magnetic stimulation test intensity on the amplitude,
      variability and reliability of motor evoked potentials.
AB  - High degrees of variability reported in Transcranial magnetic stimulation (TMS)
      assessment of corticospinal excitability (CSE) highlight the need to investigate
      its reliability as an assessment tool. This study investigated the effect of TMS
      test intensity on the amplitude, variability and test-retest reliability of motor
      evoked potentials (MEP). Twenty-five MEPs were recorded at 105%, 120%, 135%, 150%
      and 165% of resting motor threshold across three sessions in twelve participants.
      Repeated measures analysis of variance (RM-ANOVA), recruitment curve gradients
      and standardised z-value SDs were utilized to investigate the effect of TMS test
      intensity on MEP amplitude and variability. Test-retest reliability of MEP
      amplitude was assessed using RM-ANOVA and intraclass correlations (ICC). RM-ANOVA
      reported MEP amplitude significantly increased between 105-120% and 120-135% with
      non-significant increases thereafter. Recruitment curve gradients reduced as TMS
      test intensity increased. Standardised z-value SDs reported MEP amplitude
      variability reduced as TMS test intensity increased with the only significant
      reduction occurring between 120% and 135%. RM-ANOVA reported no significant
      effect of time on MEP amplitude, indicating agreement between sessions. ICCs
      indicated significant intra- and inter-session reliability for all TMS test
      intensities except for 105%. The only significant reduction in variability and
      final significant increase in MEP amplitude occurred between the same TMS test
      intensities. Reduced variability and increased reliability at higher TMS test
      intensities validate the use of higher TMS test intensities to assess changes in
      CSE in future research. To increase accuracy in capturing true changes in CSE we
      recommend assessing changes in CSE across a range of TMS test intensities.

PMID- 30194018
TI  - Neighborhood, social cohesion, and the Elderly's depression in Shanghai.
AB  - Neighborhood plays an important role in the provision of elderly care in the
      context of rapid population aging and dwindling traditional family support in
      China. This study investigates the association between neighborhood
      characteristics and depression and its mechanisms among older adults in Shanghai,
      focusing on social cohesion and social engagement. Based on data from the first
      wave of Shanghai Urban Neighborhood Survey (SUNS), we show that social cohesion
      is a channel through which neighborhood attributes are linked with the elderly's
      subjective well-being. Different from findings in Western societies, Chinese
      older adults living in neighborhoods of lower socioeconomic status are more
      likely to interact with their neighbors and thus perceive a higher level of
      social cohesion. Social cohesion, in turn, is associated with a lower rate of
      depression. We argue that housing policy in the pre-reform period that integrated
      work and housing led to the formation of unique Chinese neighborhoods, and that
      those living in socioeconomically disadvantaged neighborhoods have strong social
      ties, which moderate the negative consequences of living in a disadvantaged one.
      Moreover, a neighborhood with a lower dependency ratio provides more
      opportunities for volunteer participation which significantly associates with
      increased social cohesion and decreased depressive symptoms.

PMID- 30194019
TI  - Foreign body sensation: A rare case of dysphagia lusoria in a healthy female.
AB  - Dysphagia lusoria is a rare disease due to an aberrant right subclavian artery
      that passes posteriorly between the esophagus and the spine. David Bayford coined
      the term itself meaning "freak or jest of nature" in 1761 describing a case in
      which the patient had long term dysphagia that eventually led to death. Most
      cases of dysphagia are due to an aberrant right subclavian artery running
      posterior to and causing esophageal compression, but only 20-40% of aberrant
      arteries actually lead to trachea-esophageal symptoms, including dysphagia. The
      majority of patients with an aberrant right subclavian artery are asymptomatic.
      Treatment for dysphagia lusoria varies depending on the severity of the symptoms.
      Dietary modifications are recommended in patients with mild to moderate symptoms
      while vascular reconstruction is necessary for patients with severe symptoms. We
      present a 44-year-old female who was diagnosed with dysphagia lusoria due to a
      right-sided aortic arch and aberrant left subclavian artery (ALSA) with
      aneurysmal dilation. Right aortic arch with ALSA is an uncommon arch anomaly, and
      only occurs in about 0.05% of the population. Prior case reports of dysphagia
      lusoria differ in that they did not report patients with an uncommon presentation
      of dysphagia lusoria with aneurysmal dilatation nor was the patient diagnosed in
      the emergency department.

PMID- 30194020
TI  - Thyroid stimulating hormone testing in emergency department evaluation of
      patients with atrial fibrillation and various psychiatric diagnoses.
AB  - BACKGROUND: Previous studies of thyroid stimulating hormone (TSH) levels in
      Emergency Department (ED) patients largely have centered on patients with atrial
      fibrillation (AF). In our ED patients with AF as well as patients with
      Psychiatric diagnoses (psych) are screened. The purpose of the present study was
      to compare TSH levels in the 2 groups. Our hypotheses were that an abnormal TSH
      and/or AF predicted the need for hospital admission and that TSH is more likely
      decreased in AF and increased in psych patients. METHODS: Our goal in the study
      was to compare the use of TSH testing in two ED populations, AF vs. psych
      patients. The study was a cross sectional cohort of AF vs. psych patients who had
      TSH levels drawn in the ED over a two year period. Our laboratory ranges were
      used to determine high vs. low TSH. Two chart examiners collected data after a
      training process. Charts were reviewed extracting demographic data, TSH levels,
      outcome (admit vs. discharge), history of AF, thyroid disease, psych diagnoses,
      presence of CHF, diabetes, hypertension. We compared AF vs. Psych groups using
      chi square and t-tests for parametric data. Odds ratios were calculated for
      comparisons between the 2 groups. For non-parametric data Mann Whitney U was
      used. A logistic regression was performed with the outcome of admission vs.
      discharge to find predictors of hospital admission. Kappa was calculated for
      inter-rater agreement. An a priori power analysis showed 80% power with 2 groups
      of 100 with an absolute difference of 20% between the 2 groups. RESULTS: 252
      patients were included, 101 with AF and 152 Psych. Demographics differed in age
      only with AF patients being older. Mean TSH for AF vs. 2.4 for AF, 2.9 for psych
      (NS) with no differences in percentages with high or low TSH in the 2 groups.
      Fifty-three patients had abnormal TSH levels (21%), 27% of AF and 17% of Psych
      patients (NS). There were significant differences in incidence of CHF, DM, HTN,
      and tachycardia with more in the AF group (P < 0.001). Significantly more of the
      psych patients had a history of hypothyroidism (OR 2.28). Our logistic regression
      showed that taking into account demographics including age, the only predictors
      of admission were the presence of CHF (aOR 18.6) and having a diagnosis of AF
      (aOR 4.0). CONCLUSION: There were no differences in TSH levels between the 2
      groups. Twenty-one percent had an abnormal level. CHF and AF predicted hospital
      admission on regression analysis. Many with these AF or Psych diagnoses had
      abnormal ED TSH levels that could be useful in diagnosis, maintenance, or
      continuous treatment for their conditions diagnoses.

PMID- 30194021
TI  - Amplitude screening improves performance of AMSA method for predicting success of
      defibrillation in swine model.
AB  - PURPOSE: A novel amplitude screening method, termed Optimal Amplitude Spectrum
      Area (Opt-AMSA) with the aim of improving the performance of the Amplitude
      Spectrum Area (AMSA) method, was proposed to optimize the timing of
      defibrillation. We investigated the effects of the Opt-AMSA method on the
      prediction of successful defibrillation when compared with AMSA in a porcine
      model of ventricular fibrillation (VF). METHOD: 60 male domestic pigs were
      untreated in the first 10 min of VF, then received cardiopulmonary resuscitation
      (CPR) for 6 min. Values of Opt-AMSA and AMSA were calculated every minute before
      defibrillation. Linear regression was used to evaluate the correlation between
      Opt-AMSA and AMSA. Receiver Operating Characteristic (ROC) analysis was conducted
      for the two methods and to compare their predictive values. RESULTS: The values
      of both AMSA and Opt-AMSA gradually decreased over time during untreated VF in
      all animals. The values of both methods of defibrillation were slightly increased
      after the implementation of CPR in animals that were successfully resuscitated,
      while there were no significant changes in either method in those who ultimately
      failed to resuscitate. The significant positive correlation between Opt-AMSA and
      AMSA was shown by Pearson correlation analysis. ROC analysis showed that Opt-AMSA
      (AUC = 0.87) significantly improved the performance of AMSA (AUC = 0.77) to
      predict successful defibrillation (Z = 2.27, P < 0.05). CONCLUSION: Both the Opt
      AMSA and AMSA methods showed high potential to predict the success of
      defibrillation. Moreover, the Opt-AMSA method improved the performance of the
      AMSA method, and may be a promising tool to optimize the timing of
      defibrillation.

PMID- 30194022
TI  - Uveitis and acute glaucoma as first presenting symptoms of sarcoidosis in a
      healthy male.
AB  - Sarcoidosis is a disease that causes noncaseating granulomas in tissues such as
      the lungs, heart, skin, and eyes. Sarcoidosis is often found through chest x-ray
      or lesions in the skin and eyes. In over half of patients the disease is detected
      incidentally by radiographic abnormalities on a routing chest x-ray prior to
      development of any symptoms. The disease varies in incidence among geographic
      regions and can also aggregate in families. It is more common in African
      Americans who have a lifetime-estimated risk of 2.4 percent compared to a
      lifetime risk of 0.85 percent in whites. Multiple cases have been reported on
      sarcoidosis with eye involvement, especially uveitis. We present a healthy 36
      year-old male with no past medical who initial presentation of sarcoidosis was
      uveitis with acute angle closure glaucoma. To our knowledge this is the first
      reported case of sarcoidosis with this presentation.

PMID- 30194023
TI  - RN assessment of the inferior vena cava diameter to determine intravascular
      volume using bedside ultrasound.

PMID- 30194024
TI  - One-Year Cardiovascular Outcomes in Patients With Peripartum Cardiomyopathy.
AB  - BACKGROUND: Peripartum cardiomyopathy (PPCM) is an important cause of obstetrical
      morbidity. Few large national studies have investigated the cardiovascular
      outcomes of women with PPCM, particularly beyond the immediate postpartum period.
      We examined the cardiovascular outcomes of 1-year survivors of PPCM in a large
      commercially insured population. METHODS AND RESULTS: A retrospective cohort
      study was conducted with the use of administrative claims from patients aged 15
      54 years insured by a national commercial payer during 2005-2012. Women with PPCM
      were identified and matched by means of propensity score modeling to a control
      cohort of women undergoing childbirth without cardiovascular complications by
      demographics, comorbidities, and delivery year. Incidence of cardiovascular
      complications was measured from 11 to 365 days after delivery. A total of 975
      women with PPCM were included in the study. At 1 year after delivery, the most
      common major adverse cardiovascular events (MACEs) among the PPCM group were
      venous thromboembolism (2.2% vs 0.4%; P = .001), subsequent heart failure
      hospitalization (1.6% vs 0.1%; P < .001), and atrial fibrillation (1.0% vs 0%; P
      = .008). The PPCM cohort had a greater incidence of MACEs compared with matched
      control subjects (6.3% vs 0.6%; P < .001). CONCLUSIONS: In PPCM survivors at 1
      year, substantial morbidity continues to occur beyond the peripartum period, with
      venous thromboembolism and subsequent heart failure hospitalization being the
      most common complications.

PMID- 30194025
TI  - Does simultaneous bilateral total joint arthroplasty increase deep infection risk
      compared to staged surgeries? A meta-analysis.
AB  - BACKGROUND: Several studies have compared the incidence of periprosthetic joint
      infection (PJI) between simultaneous bilateral total joint arthroplasty (SBTJA)
      and staged bilateral total joint arthroplasty (StBTJA) patients following primary
      total joint arthroplasty. However, these studies lacked statistical power. AIM:
      To determine by meta-analysis whether SBTJA increases deep infection risk
      compared to StBTJA. METHODS: All studies were retrieved from PubMed, Embase,
      Cochrane Library databases, Web of Science, PEDro, CINAHL, SPORTDiscus, and
      Scopus. A meta-analysis was conducted to compare PJI rate between SBTJA and
      StBTJA patients. FINDINGS: Overall, there were 16 studies with 36,765 patients
      who underwent SBTJA and 71,558 patients who underwent StBTJA. The pooled data
      showed that the PJI rate of SBTJA was lower than that of StBTJA (0.84% vs 1.57%;
      odds ratio (OR): 0.57; 95% confidence interval (CI): 0.49-0.66; heterogeneity, I2
      = 0%; P = 0.74). In subgroup analysis, the pooled data revealed that there was no
      significant difference between SBTJA and StBTJA groups for PJI if the two groups
      had similar baseline demographics (four studies; OR: 0.55; 95% CI: 0.21-1.40;
      heterogeneity, I2 = 0%; P = 0.77). The pooled data showed that the PJI rate of
      SBTJA patients was comparable with that of StBTJA patients within a three-month
      staging interval (three studies; OR: 1.22; 95% CI: 0.38-3.88; heterogeneity, I2 =
      0%; P = 0.42). CONCLUSION: SBTJA does not increase the risk of subsequent PJI
      compared to StBTJA. Further studies are needed to provide higher quality evidence
      to evaluate the two modes of procedure.

PMID- 30194026
TI  - Self-diagnosis of a triple trouble.

PMID- 30194027
TI  - Allogeneic Hematopoietic Cell Transplantation in Patients Aged 50Years or Older
      with Severe Aplastic Anemia.
AB  - We report on 499 patients with severe aplastic anemia aged >= 50years who
      underwent hematopoietic cell transplantation (HCT) from HLA-matched sibling (n =
      275, 55%) or HLA-matched (8/8) unrelated donors (n = 187, 37%) between 2005 and
      2016. The median age at HCT was 57.8 years; 16% of patients were 65 to 77years
      old. Multivariable analysis confirmed higher mortality risks for patients with
      performance score less than 90% (hazard ratio [HR], 1.41; 95% confidence interval
      [CI], 1.03 to 1.92; P = .03) and after unrelated donor transplantation (HR, 1.47;
      95% CI, 1 to 2.16; P = .05). The 3-year probabilities of survival for patients
      with performance scores of 90 to 100 and less than 90 after HLA-matched sibling
      transplant were 66% (range, 57% to 75%) and 57% (range, 47% to 76%),
      respectively. The corresponding probabilities after HLA-matched unrelated donor
      transplantation were 57% (range, 48% to 67%) and 48% (range, 36% to 59%). Age at
      transplantation was not associated with survival, but grades II to IV acute graft
      versus-host disease (GVHD) risks were higher for patients aged 65years or older
      (subdistribution HR [sHR], 1.7; 95% confidence interval, 1.07 to 2.72; P = .026).
      Chronic GVHD was lower with the GVHD prophylaxis regimens calcineurin inhibitor
      (CNI) + methotrexate (sHR, .52; 95% CI, .33 to .81; P = .004) and CNI alone or
      with other agents (sHR, .27; 95% CI, .14 to .53; P < .001) compared with CNI +
      mycophenolate. Although donor availability is modifiable only to a limited
      extent, choice of GVHD prophylaxis and selection of patients with good
      performance scores are key for improved outcomes.

PMID- 30194028
TI  - Carboxymethylation of CRMP2 is associated with decreased Schwann cell myelination
      efficiency.
AB  - Pyridoxal, an active form of vitamin B6, is known to inhibit formation of
      advanced glycation end-products and protect tissues from diabetic complications.
      Here we identified that pyridoxal is a required component for establishing
      Schwann cell myelination in our Schwann cell-dorsal root ganglion neuron co
      culture system. When the co-culture was maintained without pyridoxal,
      carboxymethylation of collapsin response mediator protein 2 (CRMP2) became
      detectable. Carboxymethylation decreased the affinity of CRMP2 to bind with
      microtubules, indicating that carboxymethylation affected CRMP2 function. These
      results suggest that carboxymethylation of CRMP2 may be an indicator of
      dysfunction caused by glycation which is observed in pathological conditions,
      including diabetic neuropathy.

PMID- 30194029
TI  - Inhibition of collapsin response mediator protein-2 phosphorylation ameliorates
      motor phenotype of ALS model mice expressing SOD1G93A.
AB  - Amyotrophic lateral sclerosis (ALS) is an adult-onset neurological disease
      characterized by the selective degeneration of motor neurons leading to paralysis
      and immobility. Missense mutations in the gene coding for the Cu2+/Zn2+
      superoxide dismutase 1 (SOD1) accounts for 15-20% of familial ALS, and mice
      overexpressing ALS-linked SOD1 mutants have been frequently used as an animal
      model for ALS. Degeneration of motor neurons in ALS progresses in a manner called
      "dying back", in which the degeneration of synapses and axons precedes the loss
      of cell bodies. Phosphorylation of collapsin response mediator protein 2 (CRMP2)
      is implicated in the progression of neuronal/axonal degeneration of different
      etiologies. To evaluate the role of CRMP2 phosphorylation in ALS pathogenesis, we
      utilized CRMP2 S522A knock-in (CRMP2ki/ki) mice, in which the serine residue 522
      was homozygously replaced with alanine and thereby making CRMP2 no longer
      phosphorylatable by CDK5 or GSK3B. We found that the CRMP2ki/ki/SOD1G93A mice
      showed delay in the progression of the motor phenotype compared to their SOD1G93
      Tg littermates. Histological analysis revealed that the CRMP2ki/ki/SOD1G93A mice
      retained more intact axons and NMJs than their SOD1G93A-Tg littermates. These
      results suggest that the phosphorylation of CRMP2 may contribute to the axonal
      degeneration of motor neurons in ALS.

PMID- 30194030
TI  - Current Use of and Indications for Robot-assisted Surgery in Paediatric Urology.
AB  - : The use of robot-assisted surgery (RAS) by paediatric urologists is increasing.
      This mini review looks at the current status of RAS in paediatric urology. The
      challenges involved in RAS use in children are reviewed, as well as the
      indications for and feasibility of procedures performed and, where possible,
      outcomes with RAS. PATIENT SUMMARY: The current status of robot-assisted surgery
      (RAS) in paediatric urology, together with the challenges in using RAS for
      children is outlined in this mini review. Innovative adaptation has pushed the
      boundaries as regards the feasibility of RAS procedures in children with good
      outcomes.

PMID- 30194031
TI  - ODM-204, a Novel Dual Inhibitor of CYP17A1 and Androgen Receptor: Early Results
      from Phase I Dose Escalation in Men with Castration-resistant Prostate Cancer.
AB  - BACKGROUND: Most prostate cancer patients develop castration-resistant prostate
      cancer (CRPC) after androgen deprivation therapy treatment. CRPC growth is
      mediated mostly by androgen receptor signalling driven by primary androgens
      synthesised largely by the CYP17A1 enzyme. OBJECTIVE: To evaluate the safety
      profile and dose-limiting toxicities of ODM-204. DESIGN, SETTING, AND
      PARTICIPANTS: In this open, uncontrolled, nonrandomised, multicentre,
      tolerability and pharmacokinetic first-in-man phase I dose escalation study,
      patients with metastatic CRPC were randomised to receive ODM-204 in sequential
      cohorts of five dose levels (ie, 50, 100, 200, 300, and 500mg twice daily)
      concomitantly with prednisone. INTERVENTION: ODM-204, a novel, orally
      administered, investigational, nonsteroidal dual inhibitor of CYP17A1 and
      androgen receptor. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: ODM-204 plasma
      concentrations, serum testosterone, and prostate-specific antigen (PSA) levels
      were evaluated and imaging of lesions was performed. RESULTS AND LIMITATIONS: Of
      the 23 patients enrolled into the study, 60.9% experienced mild adverse effects
      considered to be related to the study treatment, which were fatigue,
      increased/decreased appetite, nausea, asthenia, diarrhoea, and weight decrease.
      ODM-204 area under the curve (AUC0-12) values increased dose dependently until
      the 300mg dose. The AUC was lower on day 8 after repeated dosing compared with
      day 1 from the 200mg dose upwards. Decreases in testosterone levels were seen
      with ODM-204 treatment confirming androgen deprivation. Of the patients, 13% also
      demonstrated a >50% decrease in PSA at week 12 and continued ODM-204 treatment
      for over a year. CONCLUSIONS: ODM-204 was well tolerated up to the highest
      evaluated dose. There were decreases in both testosterone and PSA levels,
      suggesting preliminary antitumour activity in the treatment of CRPC. The
      pharmacokinetic properties of the molecule, however, prevent further development.
      PATIENT SUMMARY: This study looked at the safety of ODM-204, a novel dual
      inhibitor of CYP17A1 and the androgen receptor, in castration-resistant prostate
      cancer patients. ODM-204 treatment was found to be well tolerated, and it also
      reduced both serum testosterone and prostate-specific antigen levels, but the
      properties of the molecule prevent further development.

PMID- 30194032
TI  - Does Solid Organ Transplantation Affect Male Reproduction?
AB  - Patients undergoing solid organ transplantation have experienced increased graft
      survival rates over the past several decades. With increased longevity making
      fatherhood a viable option, many patients desire to pursue this path. However,
      many patients and practitioners are likely unaware of the feasibility and safety
      for a man on a transplant immunosuppression regimen to safely pursue fatherhood.
      In this review, we discuss effects of organ transplantation and post
      transplantation treatment on male hormones, fertility, and the risk to potential
      offspring. Briefly, providers should be aware that organ transplant recipients
      may be at an increased risk for hypogonadism and erectile dysfunction, but
      fathering a child is a realistic and safe aspiration. PATIENT SUMMARY: In this
      mini-review, we discuss the effects of solid organ transplantation (such as lung,
      heart, kidney, and liver) on a man's sexual health, and his ability to have
      children. We focus on the most common problems encountered by patients after
      their transplant, and the effects of medications.

PMID- 30194033
TI  - Optogenetic precision toolkit to reveal form, function and connectivity of single
      neurons.
AB  - All-optical methods enable the control and monitoring of neuronal activity with
      minimal perturbation of the system. Although imaging and optogenetic
      manipulations can be performed at cellular resolution, the morphology of single
      cells in a dense neuronal population has often remained unresolvable. Here we
      describe in detail two recently established optogenetic protocols for systematic
      description of function and morphology of single neurons in zebrafish. First, the
      Optobow toolbox allows unbiased mapping of excitatory functional connectivity.
      Second, the FuGIMA technique enables selective labeling and anatomical tracing of
      neurons that are responsive to a given sensory stimulus or correlated with a
      specific behavior. Both strategies can be genetically targeted to a neuronal
      population of choice using the Gal4/UAS system. As these in vivo approaches are
      non-invasive, we envision useful applications for the study of neuronal
      structure, function and connectivity during development and behavior.

PMID- 30194034
TI  - Biomarker Clinical Trials in Lung Cancer: Design, Logistics, Challenges, and
      Practical Considerations.
AB  - Treatment for lung cancer has evolved in the past 3 decades starting with
      platinum-based chemotherapy as the standard of care, regardless of histology, in
      the early 1990s to the current age of biomarker-driven therapy. Consequently,
      clinical trials in lung cancer have evolved in response to this new shift of
      paradigm, leading to novel approaches that simultaneously shorten the development
      process and allow evaluation of multiple patient cohorts. Herein, we provide an
      overview of the landscape of lung cancer clinical trials in the era of targeted
      therapies, precision medicine, and biomarkers. Specific trials are given as
      examples to illustrate the design paradigms. The paper is organized by drug
      development phases starting with early-phase biomarker discovery to proof-of
      concept trials to definitive trials. We also present some thoughts on future
      directions.

PMID- 30194035
TI  - Survival Patterns for Patients with Resected N2 Non-Small Cell Lung Cancer and
      Postoperative Radiotherapy: A Prognostic Scoring Model and Heat Map Approach.
AB  - INTRODUCTION: The positive-to-resected lymph node ratio (LNR) predicts survival
      in many cancers, but little information is available on its value for patients
      with N2 NSCLC who receive postoperative radiotherapy (PORT) after resection. We
      tested the applicability of prognostic scoring models and heat mapping to predict
      overall survival (OS) and cancer-specific survival (CSS) in patients with
      resected N2 NSCLC and PORT. METHODS: Our test cohort comprised patients
      identified from the Surveillance, Epidemiology, and End Results database with N2
      NSCLC who received resection and PORT in 2000-2014. Prognostic scoring models
      were developed to predict OS and CSS using Cox regression; heat maps were
      constructed with corresponding survival probabilities. Recursive partitioning
      analysis was applied to the Surveillance, Epidemiology, and End Results data to
      identify the optimal LNR cutoff point. Models and cutoff points were further
      tested in 183 similar patients treated at The University of Texas M. D. Anderson
      Cancer Center in 2000-2015. RESULTS: Multivariate analyses revealed that low LNR
      independently predicted better OS and CSS in patients with resected N2 NSCLC who
      received PORT. CONCLUSIONS: LNR can be used to predict survival of patients with
      resected N2 NSCLC followed by PORT. This approach, which to our knowledge is the
      first application of heat mapping of positive and negative lymph nodes, was
      effective in estimating 3-, 5-, and 10-year OS probabilities.

PMID- 30194036
TI  - Adenocarcinoma of the Lung in Childhood and Adolescence: A Systematic Review.
AB  - Primary lung cancer is extremely rare in children. It often presents with
      metastatic disease and carries a poor prognosis. Adenocarcinoma is the most
      common type of bronchogenic carcinoma in children and adults. Our aim was to
      systematically review the presenting features, approach to diagnosis and
      management, as well as the outcomes of primary pediatric adenocarcinoma of the
      lung. This systematic review was prospectively registered with PROSPERO. The
      following databases were searched: Medline, Embase, Web of Science, and Scopus
      for English language cases of primary pediatric adenocarcinoma of the lung. Forty
      eight studies were included, comprising 62 patients with adenocarcinoma and 21
      cases of adenocarcinoma in situ. Presenting features were nonspecific, with cough
      and dyspnea the main symptoms at diagnosis. The majority of patients with
      adenocarcinoma had metastatic disease at diagnosis. Surgery was the most common
      form of management. More than half the patients with adenocarcinoma had died at
      final follow-up, whereas 5 of 21 with adenocarcinoma in situ died. Medical
      management did not improve outcomes, except for two ALK receptor tyrosine kinase
      (ALK)-rearranged adenocarcinomas that responded to ALK inhibitor therapy alone.
      Primary pediatric adenocarcinoma of the lung is a rare entity which often
      presents with metastatic disease and portends a poor prognosis. Surgery is
      associated with disease-free status, although new agents such as ALK-inhibitors
      are able to prolong life without surgical management.

PMID- 30194037
TI  - Enterococcus faecium tolerance to isopropanol: from good science to
      misinformation.

PMID- 30194038
TI  - SLC35A2-related congenital disorder of glycosylation: Defining the phenotype.
AB  - We aim to further delineate the phenotype associated with pathogenic variants in
      the SLC35A2 gene, and review all published literature to-date. This gene is
      located on the X chromosome and encodes a UDP-galactose transporter. Pathogenic
      variants in SLC35A2 cause a congenital disorder of glycosylation. The condition
      is rare, and less than twenty patients have been reported to-date. The phenotype
      is complex and has not been fully defined. Here, we present a series of five
      patients with de novo pathogenic variants in SLC35A2. The patients' phenotype
      includes developmental and epileptic encephalopathy with hypsarrhythmia, facial
      dysmorphism, severe intellectual disability, skeletal abnormalities, congenital
      cardiac disease and cortical visual impairment. Developmental and epileptic
      encephalopathy with hypsarrhythmia is present in most patients with SLC35A2
      variants, and is drug-resistant in the majority of cases. Adrenocorticotropic
      hormone therapy may achieve partial or complete remission of seizures, but the
      effect is usually temporary. Isoelectric focusing of transferrins may be normal
      after infancy, therefore a congenital disorder of glycosylation should still be
      considered as a diagnosis in the presence of a suggestive phenotype. We also
      provide evidence that cortical visual impairment is part of the phenotypic
      spectrum.

PMID- 30194039
TI  - Benign nocturnal alternating hemiplegia of childhood: A clinical and
      nomenclatural reappraisal.
AB  - OBJECTIVE: To describe the clinical spectrum of benign nocturnal alternating
      hemiplegia of childhood (BNAHC) including long-term follow-up data of previously
      published cases and to propose an underlying genetic cause of this disorder.
      METHODS: We studied the medical data of two novel patients, reviewed the
      literature on BNAHC, and gathered information of the most recent follow-up of
      published cases regarding the course of episodes, further development, attempted
      drugs, ancillary investigations, and sequelae. RESULTS: All patients, i.e. two
      novel cases and twelve patients identified in the literature (13 boys, 1 girl,
      age at onset four months to three years), experienced episodes of hemiplegia
      during nocturnal or daytime sleep heralded by inconsolable crying. Possible
      triggers included stress and sleep deprivation. Eleven of fourteen patients had a
      family history of migraine or 'intermittent headache' and two sets of siblings
      are reported. In one case, exome sequencing revealed a heterozygous 16p11.2
      deletion involving 33 genes, including the PRRT2 gene. EEG showed ictal and/or
      interictal contralateral slowing in four patients. Treatment efficacy was
      generally disappointing. A complete disappearance of attacks appeared in nearly
      all cases at most recent follow-up. In a remarkably high number of cases (10/14,
      71%), hyperactive behaviour was reported during follow-up. CONCLUSION: We
      underscore the phenotypic homogeneity including the self-limiting course of BNAHC
      episodes and suggest the condition be renamed 'benign childhood hemiplegia during
      sleep' (BCHS). We propose a role for the PRRT2 gene and the resulting neuronal
      hyperexcitability as one of its possible underpinning mechanisms and discuss the
      clinical similarities of BCHS with the recognized PRRT2-related disorders.

PMID- 30194040
TI  - The strength and spread of the electric field induced by transcranial rotating
      permanent magnet stimulation in comparison with conventional transcranial
      magnetic stimulation.
AB  - BACKGROUND: Weak or low intensity transcranial stimulation of the brain, such as
      low field magnetic stimulation and electrical stimulation, can produce
      significant functional and therapeutic neuromodulatory effects. NEW METHOD: We
      have recently developed a portable wearable multifocal brain stimulator called
      transcranial rotating permanent magnet stimulator (TRPMS) that uses rapidly
      spinning high field strength permanent magnets attached to a cap. It produces
      oscillatory stimuli of different frequencies and patterns. Here we compared the
      strengths and spatial profiles of the changing magnetic fields of a figure-of
      eight transcranial magnetic stimulator (TMS) coil, a TRPMS prototype, and a
      scaled-up version of TRPMS. We measured field strengths and directions of
      voltages induced in a magnetic field sensor oriented along all three orthogonal
      axes. RESULTS AND COMPARISON WITH EXISTING METHODS: The spatial spread of the
      TRPMS-induced electric field is more restricted, and its shape and strength vary
      less with the orientation of the inductance than TMS. The maximum voltage induced
      by the current prototype is ~7% of the maximal TMS output at depths corresponding
      to the human cerebral cortex from the scalp surface. This field strength can be
      scaled up by a factor ~8 with a larger diametrically magnetized magnet. These
      comparative data allow us to estimate that intracortical effects of TRPMS could
      be stronger than other low intensity stimulation methods. CONCLUSIONS: TRPMS
      might enable greater uniformity, consistency and focality in stimulation of
      targeted cortical areas subject to significant anatomical variability. Multiple
      TRPMS microstimulators can also be combined to produce patterned multifocal
      spatiotemporal stimulation.

PMID- 30194041
TI  - Real-time non-invasive in vivo visible light detection of cortical spreading
      depolarizations in mice.
AB  - BACKGROUND: Cortical spreading depolarization (CSD) is a phenomenon classically
      associated with migraine aura. CSDs have also been implicated in secondary injury
      following ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage, and
      traumatic brain injury; however, most investigations involving these disease
      processes do not account for the occurrence of CSDs. A major barrier to detection
      of CSDs in experimental models is that currently validated methods are invasive
      and require specialized equipment and a high level of expertise to implement. NEW
      METHOD: We present a low-cost, easy-to-implement approach to the detection of
      CSDs in the mouse through full-thickness intact skull. Our method uses the
      optical intrinsic signal from white light illumination (OIS-WL) and allows for
      real-time in vivo detection of CSDs using readily available USB cameras. RESULTS:
      OIS-WL detected 100% of CSDs that were seen with simultaneous electrode recording
      (69 CSDs in 28 mice), laser Doppler flowmetry (82 CSDs in 10 mice), laser speckle
      flowmetry (68 CSDs in 25 mice), or combined electrode recording plus laser
      speckle flowmetry (29 CSDs in 20 mice). OIS-WL detected 1 additional CSD that was
      missed by laser Doppler flowmetry. COMPARISON WITH EXISTING METHODS: OIS-WL is
      less invasive than electrophysiological recordings and easier to implement than
      laser speckle flowmetry. Moreover, it provides excellent spatial and temporal
      resolution for dynamic imaging of CSDs in the setting of brain injury.
      CONCLUSIONS: Detection of CSDs with an inexpensive USB camera and white light
      source provides a reliable method for the in vivo and non-invasive detection of
      CSDs through unaltered mouse skull.

PMID- 30194042
TI  - An automated method for the quantification of transgene expression in motor axons
      of the peripheral nerve.
AB  - BACKGROUND: Determination of transgene expression in motor axons of peripheral
      nerves is important in evaluating the effectiveness of viral transduction.
      Currently only manual and semi-automatic methods of quantification have been
      employed for quantification in immunolabeled nerve sections, but automatic
      methods exist for axon counting only in brightfield sections. Manual and semi
      automatic methods can suffer from inter- and intraobserver bias, sampling bias
      and can be time consuming to implement. NEW METHOD: A fully automated method
      using ImageJ and the Nucleus Counter plugin was developed to quantify the
      fraction of green fluorescent protein (GFP) labeled acetylcholine transferase
      positive axons in triple immunolabeled peripheral nerve sections. This method
      utilizes the Nucleus Counter to generate axonal regions of interest which are
      quantified for colocalization with GFP expression and nonoverlap with Laminin.
      Thresholding using histograms generated from control animals is used to remove
      noise. RESULTS: The automated method is able to successfully distinguish
      transgenic GFP expressing mice from wild type. Using computer generated
      peripheral nerve sections, the automated method has less than 5% error at signal
      to-noise ratios greater than 10% of baseline. COMPARISONS WITH EXISTING METHODS:
      This method has comparable performance in false positive rates (<1%) and a 95%
      predictive interval that closely matches existing fully automated methods for
      quantification in brightfield sections. It outperforms the intra- and
      interobserver differences of manual and semi-automated methods for
      quantification. CONCLUSIONS: This automated quantification method provides a fast
      and robust means of determining the fraction of labeled axons in peripheral nerve
      sections.

PMID- 30194043
TI  - A web-based application for generating 2D-unfolded cortical maps to analyze the
      location and extent of cortical lesions following traumatic brain injury in adult
      rats.
AB  - BACKGROUND: Both the type and severity of functional impairments caused by damage
      to the cerebral cortex depend on the functional cortical areas and networks
      affected, as well as the lesion extent and type. NEW METHOD: To accelerate the
      laborious quantitative analysis of cortical lesion location and size, we created
      user-friendly software that generates two-dimensional unfolded cortical maps of
      the lesions in adult rats. The program imports and superimposes simple user-made
      measurements, e.g., from histologic sections, on a template. The software then
      quantifies the total lesion area and the area of damage in each cortical
      cytoarchitechtonic region. To validate the accuracy of the software, we compared
      computer-generated maps with manually created unfolded maps from 32 rats with
      lateral fluid-percussion-induced traumatic brain injury. RESULTS: The total area
      of the cortical lesions varied from 7.37 to 38.45 mm2 in the automated analysis
      and from 7.26 to 38.97 mm2 in the manual analysis (p > 0.05). The Pearson
      correlation coefficient between the automated and manual analyses was 0.998 (p <
      0.001). The mean difference between the automated and manual measurements was
      0.50 +/- 0.69 mm2 (range 0.00-3.30 mm2). The slight differences between the
      analyses related to human error in positioning the measurements to the
      anteroposterior coordinates on the template map. COMPARISON WITH EXISTING
      METHODS: Compared with the manual method, the automated method accurately and
      quickly generates unfolded cortical maps of lesioned cortical areas. CONCLUSIONS:
      Application provides a novel tool for accurately positioning the lesioned area on
      the cortical mantle and quantifying the lesion area in histologic sections or
      magnetic resonance images.

PMID- 30194044
TI  - Vegetation pattern formation in seminal systems due to internal competition
      reaction between plants.
AB  - Self-organised patterns of vegetation are a characteristic feature of semi
      deserts. In this paper, we find the internal competition reaction between plants
      can lead to the formation of spatial vegetation patterns, which is different from
      the normal formation mechanism of long-range competition and short-range
      facilitation. It is also found that the internal competition between biomass has
      an effect on the characters of banded vegetation. In particular, it is shown that
      the internal competition reaction leads to the decrease of the migration speed
      and the increase of the wavelength of the stripe patterns.

PMID- 30194045
TI  - Global stability analysis and optimal control therapy of blood cell production
      process (hematopoiesis) in acute myeloid leukemia.
AB  - In this paper we analyze the global stability of a coupled model for Acute
      Myeloid Leukemia and propose a therapy approach based on an optimal control
      strategy. Firstly, based on the positivity of the model, stability of trivial
      solutions for healthy and cancerous cell subsystems is assessed. To this end we
      use new Lyapunov functionals and take into account the interconnection between
      cell populations. Secondly, stability conditions for healthy situation in
      interconnected model are established by using Nyquist criterion. And thirdly, we
      design an optimal control based therapy that aims to eradicate cancerous cells
      and minimize the side effects of the treatment on healthy ones. After showing the
      existence of an optimal control, this one is determined by using Pontriagyn's
      principal. We assess the effect of interconnection between healthy and cancerous
      cells on their dynamics and on the stability conditions for different cases. The
      behavior of the system in open loop and with application of the optimal control
      therapy is illustrated by simulation and results are biologically explained and
      motivated.

PMID- 30194046
TI  - Microbiome profiling reveals gut dysbiosis in a transgenic mouse model of
      Huntington's disease.
AB  - Huntington's disease (HD) is a progressive neurodegenerative disorder caused by a
      trinucleotide repeat expansion in the huntingtin (HTT) gene, which is expressed
      ubiquitously throughout the brain and peripheral tissues. Whilst the focus of
      much research has been on the cognitive, psychiatric and motor symptoms of HD,
      the extent of peripheral pathology and its potential impact on central symptoms
      has been less intensely explored. Disruption of the gastrointestinal microbiome
      (gut dysbiosis) has been recently reported in a number of neurological and
      psychiatric disorders, and therefore we hypothesized that it might also occur in
      HD. We have used 16S rRNA amplicon sequencing to characterize the gut microbiome
      in the R6/1 transgenic mouse model of HD, relative to littermate wild-type
      controls. We report that there is a significant difference in microbiota
      composition in HD mice at 12 weeks of age. Specifically, we observed an increase
      in Bacteriodetes and a proportional decrease in Firmicutes in the HD gut
      microbiome. In addition, we observed an increase in microbial diversity in male
      HD mice, compared to wild-type controls, but no differences in diversity were
      observed in female HD mice. The gut dysbiosis observed coincided with impairment
      in body weight gain despite higher food intake as well as motor deficits at 12
      weeks of age. Gut dysbiosis was also associated with a change in the gut
      microenvironment, as we observed higher fecal water content in HD mice at 12
      weeks of age. This study provides the first evidence of gut dysbiosis in HD.

PMID- 30194047
TI  - Nigrostriatal pathology with reduced astrocytes in LRRK2 S910/S935
      phosphorylation deficient knockin mice.
AB  - Leucine-rich repeat kinase 2 (LRRK2) is genetically implicated in both familial
      and sporadic Parkinson's disease (PD). Moreover, LRRK2 has emerged as a
      compelling therapeutic target for the treatment of PD. Consequently, there is
      much interest in understanding LRRK2 and its role in PD pathogenesis. LRRK2 is
      constitutively phosphorylated on two serines, S910 and S935, that are required
      for interaction of LRRK2 with members of the 14-3-3 family of scaffolding
      proteins. Pathogenic LRRK2 missense mutations impair the phosphorylation of LRRK2
      at these sites, but whether this contributes to PD pathology is unclear. To
      better understand how loss of LRRK2 phosphorylation relates to PD pathology, we
      have studied double knockin mice in which Lrrk2's serine 910 and 935 have both
      been mutated to alanine and can therefore no longer be phosphorylated.
      Nigrostriatal PD pathology was assessed in adult mice, aged mice, and mice
      inoculated with alpha-synuclein fibrils. Under all paradigms there was evidence
      of early PD pathology in the striatum of the knockin mice, namely alterations in
      dopamine regulating proteins and accumulation of alpha-synuclein. Striatal
      pathology was accompanied by a significant decrease in the number of astrocytes
      in the knockin mice. Despite striatal pathology, there was no degeneration of
      dopamine neurons in the substantia nigra and no evidence of a PD motor phenotype
      in the knockin mice. Our results suggest that modulation of LRRK2 serine 910 and
      935 phosphorylation sites may have implications for dopamine turnover and
      astrocyte function, but loss of phosphorylation at these residues is not
      sufficient to induce PD neurodegeneration.

PMID- 30194048
TI  - Sildenafil crosses the placenta at therapeutic levels in a dually perfused human
      cotyledon model.
AB  - BACKGROUND: Sildenafil already is administered during gestation in patients with
      pulmonary hypertension and is under evaluation as a treatment for several
      pregnancy complications, such as preeclampsia and intrauterine growth
      restriction. Animal studies have shown a potential therapeutic effect of the drug
      in fetuses with congenital diaphragmatic hernia, rescuing peripheral pulmonary
      vasculature, and airway phenotype. When considering this drug for evaluation in a
      clinical trial, data on effective human placental drug passage are required.
      OBJECTIVE: We quantified transplacental passage of sildenafil in the ex vivo
      dually perfused cotyledon model. STUDY DESIGN: Six placentas that were collected
      after term delivery from healthy volunteers were cannulated and perfused dually.
      Sildenafil citrate was added to the maternal circulation at 2 different
      concentrations: 500 ng/mL, which represented the maximum tolerated concentration
      (n=3), and 50 ng/mL, which represented the therapeutic concentration (n=3).
      Samples were collected from both the fetal and the maternal reservoir at 0, 6,
      30, 60, 90, 120, 150, and 180 minutes; the concentrations of sildenafil and its
      metabolite desmethyl-sildenafil were determined with the use of high performance
      liquid chromatography. The fetal/maternal concentration ratio was calculated for
      each timepoint. Transfer clearance was calculated as the rate of maternal to
      fetal passage/maternal concentration. RESULTS: Sildenafil crossed the placenta at
      both maximal and therapeutic concentrations. Maternal and fetal levels reached a
      plateau at 90-120 minutes. Transfer clearance was the highest during the first
      hour of perfusion: 3.15 mL/min (range, 2.14-3.19 mL/min) for the maximum
      tolerated concentration and 3.07mL/min (range, 2.75-3.42 mL/min) for the
      therapeutic concentration (not significant). The fetomaternal concentration ratio
      significantly increased over time, up to 0.91+/-0.16 for the maximal
      concentration and 0.95+/-0.22 for the therapeutic concentration at the end of the
      perfusion (not significant). Desmethyl-sildenafil was not detected in any sample.
      CONCLUSION: Sildenafil crosses the term placenta at a relatively high rate ex
      vivo, which suggests that there is sufficient placental transfer to reach
      clinically active fetal drug levels at the currently used maternal doses.

PMID- 30194049
TI  - Medicaid savings from the Contraceptive CHOICE Project: a cost-savings analysis.
AB  - BACKGROUND: Forty-five percent of births in the United States are unintended, and
      the costs of unintended pregnancy and birth are substantial. Clinical and policy
      interventions that increase access to the most effective reversible contraceptive
      methods (intrauterine devices and contraceptive implants) have potential to
      generate significant cost savings. Evidence of cost savings for these
      interventions is needed. OBJECTIVE: The purpose of this study was to conduct a
      cost-savings analysis of the Contraceptive CHOICE Project, which provided
      counseling and no-cost contraception, to demonstrate the value of investment in
      enhanced contraceptive care to the Missouri Medicaid program. STUDY DESIGN: The
      Contraceptive CHOICE Project was a prospective cohort study of 9256 reproductive
      age women who were enrolled between 2007 and 2011. Study follow-up was completed
      October 2013. This analysis includes 5061 Contraceptive CHOICE Project
      participants who were current Missouri Medicaid beneficiaries or were uninsured
      and reported household incomes <201% of the federal poverty line. We created a
      simulated comparison group of women who were receiving care through the Missouri
      Title X program and modeled the contraception and pregnancy outcomes that would
      have occurred in the absence of the Contraceptive CHOICE Project. Data about
      contraceptive use for the comparison group (N=5061) were obtained from the
      Missouri Title X program and adjusted based on age, race, ethnicity, and income.
      To make an accurate comparison that would account for the difference in the 2
      populations, we used our simulation model to estimate total Contraceptive CHOICE
      Project costs and total comparison group costs. We reported all costs in 2013
      dollars to account for inflation. RESULTS: Among the Contraceptive CHOICE Project
      participants who were included, the uptake of intrauterine devices and implants
      was 76.1% compared with 4.8% among the comparison group. The estimated
      contraceptive cost for the simulated Contraceptive CHOICE Project group was $4.0
      million vs $2.3 million for the comparison group. The estimated numbers of
      unintended pregnancies and births averted among the simulated Contraceptive
      CHOICE Project group compared with the comparison group were 927 and 483,
      respectively, which represented a savings in pregnancy and maternity care of $6.7
      million. We estimated that the total cost savings for the state of Missouri
      attributable to the Contraceptive CHOICE Project was $5.0 million (40.7%) over
      the project duration. CONCLUSION: A program providing counseling and no-cost
      contraception yields substantial cost savings because of the increased uptake of
      highly effective contraception and consequent averted unintended pregnancy and
      birth.

PMID- 30194050
TI  - Abruptio placentae risk and genetic variations in mitochondrial biogenesis and
      oxidative phosphorylation: replication of a candidate gene association study.
AB  - BACKGROUND: Abruptio placentae is a complex multifactorial disease that is
      associated with maternal and neonatal death and morbidity. Abruptio placentae's
      high recurrence rate, high prevalence of heritable thrombophilia among women with
      abruptio placentae, and aggregation of cases in families of women with the
      disease support the possibility of a genetic predisposition. Previous genome-wide
      and candidate gene association studies have identified single nucleotide
      polymorphisms in mitochondrial biogenesis and oxidative phosphorylation genes
      that potentially are associated with abruptio placentae risk. Perturbations in
      mitochondrial biogenesis and oxidative phosphorylation, which results in
      mitochondrial dysfunction, can lead to the impairment of differentiation and
      invasion of the trophoblast and to several obstetrics complications that include
      abruptio placentae. OBJECTIVE: The purpose of this study was to determine whether
      the results of a candidate genetic association study that indicated a link
      between DNA variants (implicated in mitochondrial biogenesis and oxidative
      phosphorylation) and abruptio placentae could be replicated. STUDY DESIGN: The
      study was conducted among participants (507 abruptio placentae cases and 1090
      control subjects) of the Placental Abruption Genetic Epidemiology study. Weighted
      genetic risk scores were calculated with the use of abruptio placentae risk
      increasing alleles of 11 single nucleotide polymorphisms in 9 mitochondrial
      biogenesis and oxidative phosphorylation genes (CAMK2B, NR1H3, PPARG, PRKCA,
      THRB, COX5A, NDUFA10, NDUFA12, and NDUFC2), which previously was reported in the
      Peruvian Abruptio Placentae Epidemiology study, a study with similar design and
      study population to the Placental Abruption Genetic Epidemiology study. Logistic
      regression models were fit to examine associations of weighted genetic risk
      scores (quartile 1, <25th percentile; quartile 2, 25-50th percentile; quartile 3,
      50-70th percentile, and quartile 4, >75th percentile) with risk of abruptio
      placentae, adjusted for population admixture (the first 4 principal components),
      maternal age, infant sex, and preeclampsia. The weighted genetic risk score was
      also modeled as a continuous predictor. To assess potential effect modification,
      analyses were repeated among strata that were defined by preeclampsia status,
      maternal age (>=35 vs 18-34 years), and infant sex. RESULTS: Abruptio placentae
      cases were more likely to have preeclampsia, shorter gestational age, and lower
      infant birthweight. Participants in quartile 2 (score, 12.6-13.8), quartile 3
      (score, 13.9-15.0) and quartile 4 (score, >=15.1) had a genetic risk score of
      1.45-fold (95% confidence interval, 1.04-2.02; P=.03), a 1.42-fold (95%
      confidence interval, 1.02-1.98; P=.04), and a 1.75-fold (95% confidence interval,
      1.27-2.42; P=7.0E-04) higher odds of abruptio placentae, respectively, compared
      with those in quartile 1 (score,<12.6; P-for trend=.0003). The risk of abruptio
      placentae was 1.12-fold (95% confidence interval, 1.05-1.19; P=3.0*1004) higher
      per 1-unit increase in the score. Among women with preeclampsia, those in
      quartile 4 had a 3.92-fold (95% confidence interval, 1.48-10.36; P=.01) higher
      odds of abruptio placentae compared with women in quartile 1. Among normotensive
      women, women in quartile 4 had a 1.57-fold (95% confidence interval, 1.11-2.21;
      P=.01) higher odds of abruptio placentae compared with those in quartile 1 (P-for
      interaction=.12). We did not observe differences in associations among strata
      defined by maternal age or infant sex. CONCLUSION: In this study, we replicated
      previous findings and provide strong evidence for DNA variants that encode for
      genes that are involved in mitochondrial biogenesis and oxidative phosphorylation
      pathways, which confers risk for abruptio placentae. These results shed light on
      the mechanisms that implicate DNA variants that encode for proteins in
      mitochondrial function that are responsible for abruptio placentae risk.
      Therapeutic efforts to reduce risk of abruptio placentae can be enhanced by
      improved biologic understanding of maternal mitochondrial biogenesis/oxidative
      phosphorylation pathways and identification of women who would be at high risk
      for abruptio placentae.

PMID- 30194051
TI  - Historical (retrospective) cohort studies and other epidemiologic study designs
      in perinatal research.
AB  - When investigators describe the study design they employed, the term
      retrospective cohort commonly is selected and commonly used incorrectly. In a
      prospective cohort, investigators enroll exposed and unexposed individuals, all
      of whom are at risk of experiencing the study outcome, and follow them forward in
      time to observe incident outcomes. In a retrospective (historical) cohort,
      investigators use preexisting data to identify exposed and unexposed individuals
      in the past, without regard to outcome status, and trace these individuals
      forward, up to and possibly including the present, to determine incident
      outcomes. Both of these designs are cohorts because they identify individuals
      based on exposure, without regard to outcome; they follow the individuals over
      time, either in the future (prospective cohort) or in the past (historical
      cohort), and they assess the incidence, not just the prevalence, of the study
      outcome. The designation of retrospective cohort is based on the presence and
      timing of follow up before the onset of research, not on the timing of the
      analysis with respect to when the data were collected and regardless of the
      original purpose for which the data were collected. In short, a prospective
      cohort study remains a prospective cohort study when analyzed for secondary
      research purposes, even if this research occurs many years after data collection.
      Because of the complex nature of modern databases and study designs and the
      inherent ambiguity of the terms retrospective and prospective, modern
      epidemiologists rarely use these terms as simple descriptors, preferring instead
      to describe what the study actually did.

PMID- 30194052
TI  - Engineering Trichoderma reesei Rut-C30 with the overexpression of egl1 at the
      ace1 locus to relieve repression on cellulase production and to adjust the ratio
      of cellulolytic enzymes for more efficient hydrolysis of lignocellulosic biomass.
AB  - Cellulose hydrolysis is a synergetic process performed sequentially by different
      cellulolytic enzymes including endoglucanases, exoglucanases and glucosidases.
      Trichoderma reesei has been acknowledged as the best cellulase producer, but
      cellulase production by T. reesei through submerged fermentation is costly due to
      intensive energy consumption associated with the process for mixing and aeration,
      since non-Newtonian fluid properties are developed with mycelial growth.
      Therefore, engineering the ratio of cellulolytic enzymes in the cocktail for more
      efficient cellulose hydrolysis is an alternative strategy for reducing cellulase
      dosage and thus saving cost in enzyme consumption for cellulose hydrolysis. In
      this study, T. reesei QS305 with high endoglucanase activity was developed from
      T. reesei Rut-C30 by replacing the transcription repressor gene ace1 with the
      coding region of endoglucanase gene egl1. Compared to T. reesei Rut-C30, T.
      reesei QS305 showed 90.0% and 132.7% increase in the activities of total
      cellulases and endoglucanases under flask culture conditions. When cellulase
      production by T. reesei QS305 was performed in the 5-L fermentor, cellulases
      activity of 10.7 FPU/mL was achieved at 108 h, 75.4% higher than that produced by
      T. reesei Rut-C30. Moreover, cellulases produced by T. reesei QS305 were more
      efficient for hydrolyzing pretreated corn stover and Jerusalem artichoke stalk.

PMID- 30194053
TI  - Molecular characterization and functional analysis of MyD88 from the tropical sea
      cucumber, Holothuria leucospilota.
AB  - In this study, a myeloid differentiation factor 88 (MyD88) named as HLMyD88 was
      identified from the sea cucumber Holothuria leucospilota. The full-length cDNA of
      HLMyD88 is 4797 bp in size, containing a 227 bp 5'-untranslated region (UTR), a
      3721 bp 3'-UTR and an 849 bp open reading frame (ORF) encoding a protein of 282
      amino acids with a deduced molecular weight of 32.25 kDa HLMyD88 contains an N
      terminal death domain and a C-terminal Toll/interluekin-1 receptor (TIR) domain
      with three highly conserved sequence motifs named as Box 1, Box 2 and Box 3. The
      results of luciferase reporter assay showed that over-expressed HLMyD88 in
      HEK293T cells could activate the transcription factors nuclear factor-kappaB (NF
      kappaB) and activator protein 1 (AP-1). Additionally, the secretion of
      proinflammatory cytokines IL-1beta and TNF-alpha in the HEK293T cells was
      increased by over-expressed HLMyD88, indicating the potential role of HLMyD88 in
      the innate immunity of sea cucumber. Moreover, we further confirmed that over
      expressed HLMyD88 could also induce apoptosis.

PMID- 30194054
TI  - Synergistic effects of dietary Bacillus sp. SJ-10 plus beta-glucooligosaccharides
      as a synbiotic on growth performance, innate immunity and streptococcosis
      resistance in olive flounder (Paralichthys olivaceus).
AB  - Bacillus sp. SJ-10 (BSJ-10) was identified from traditional Korean fermented
      fish, the previously recognized prebiotic beta-glucooligosaccharides (BGO), and
      their combination as a synbiotic were prepared to evaluate their individual and
      synergistic effects in olive flounder (Paralichthys olivaceus). Four diets (one
      control and three treatments) were formulated containing neither BSJ-10 nor BGO
      (control), 1 * 108 CFU g -1 BSJ-10 (BSJ-10), 0.1% BGO (BGO), and 1 * 108 CFU g-1
      BSJ-10 + 0.1% BGO (BSJ-10 + BGO). Triplicates of 15 fish (weight 10 +/- 0.25 g)
      were randomly allocated to the four diet groups and fed one of the diets for 8
      weeks. At the end of the experiment, fish weight gain (WG), specific growth rate
      (SGR), feed conversion ratio, and protein efficiency ratio in BSJ-10, BGO and BSJ
      10 + BGO diets were positively modulated (P < 0.05) compared with control.
      Specially, WG and SGR were significantly (P < 0.05) higher in BSJ-10 + BGO than
      that of BSJ-10 and BGO (individual component). The innate immune parameters such
      as respiratory burst, superoxide dismutase, and lysozyme activity (LSZ) of fish
      fed BSJ-10 and BSJ-10 + BGO (both groups) were significantly (P < 0.05) higher
      than the control. Moreover, myeloperoxidase activity (MPO) and LSZ of fish fed
      BSJ-10 + BGO were significantly higher compared with individual component.
      Compared with control, intestinal BSJ-10 content, expression of interleukin (IL)
      1beta in liver and kidney, and tumor necrosis factor (TNF)-alpha in liver were
      higher in both groups, but microvillus length was increased (P < 0.05) only in
      BSJ-10 + BGO. During in vivo challenge experiment with Streptococcus iniae (1 *
      108 CFU ml-1), survival rate of fish was significantly higher in all treatment
      groups versus control. Moreover, in BSJ-10 + BGO, protection against S. iniae
      infection and transcription of TNF-alpha and IL-6 in gill were significantly (P <
      0.05) higher than the individual component. Collectively, an improved WG, SGR,
      MPO, LSZ, transcription of IL-6 and TNF-alpha, and cumulative survival rate
      against streptococcosis clearly demonstrates a synergistic outcome of diet BSJ-10
      + BGO as synbiotic in olive flounder.

PMID- 30194055
TI  - Sagittaria sagittifolia polysaccharide protects against isoniazid- and rifampicin
      induced hepatic injury via activation of nuclear factor E2-related factor 2
      signaling in mice.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The Sagittaria sagittifolia L. polysaccharide
      (SSP) is a purified form of a homogeneous polysaccharide isolated from the root
      tubers of S. sagittifolia, which has been used as a protectant against
      hepatotoxicity induced by coadministration of isoniazid and rifampicin. However,
      the protective effect of SSP against isoniazid- and rifampicin-induced liver
      injury has never been studied. AIM OF THE STUDY: In this study, the
      hepatoprotective effect of SSP and its underlying mechanism were investigated in
      mice with isoniazid- and rifampicin-induced liver injury. MATERIALS AND METHODS:
      Liver injury was induced in mice by intragastric administration of isoniazid and
      rifampicin, and the mice were divided into the following six groups: standard
      control (administration of saline by gavage), model (intragastric administration
      of isoniazid and rifampicin at 100 mg/kg/day each), positive control (100
      mg/kg/day silymarin by gavage 4 h after isoniazid and rifampicin administration),
      and SSP-treated (200, 400, or 800 mg/kg/day SSP by gavage after isoniazid and
      rifampicin administration). Subsequently, blood and liver samples were collected
      from all the animals and were assessed. RESULTS: SSP significantly alleviated the
      liver injury, as evidenced by decreased activities of alanine aminotransferase,
      aspartate aminotransferase, and lactate dehydrogenase in the serum and a
      decreased level of malondialdehyde in the liver, as well as by an increased level
      of glutathione and increased activities of superoxide dismutase and catalase in
      the liver. SSP also effectively reduced the pathological tissue damage. The gene
      and protein expression of cytochrome P450 (CYP) 2E1 and CYP3A4 was inhibited by
      SSP. The gene and protein expression of nuclear factor erythroid 2-related factor
      2 (NRF2), glutamate-cysteine ligase, and heme oxygenase-1 were induced by SSP,
      whereas that of Kelch-like ECH-associated protein 1 was inhibited. CONCLUSIONS:
      SSP exerts a protective effect against isoniazid- and rifampicin-induced liver
      injury in mice. The underlying mechanisms may involve activation of NRF2 and its
      target antioxidant enzymes and inhibition of the expression of CYPs.

PMID- 30194056
TI  - Endothelium corneum gigeriae galli extract inhibits calcium oxalate formation and
      exerts anti-urolithic effects.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese Medicine is preferred because
      of its safety and minimal/reduced side effects. Endothelium Corneum Gigeriae
      Galli (ECGG) extract, a traditional Chinese drug consisting of the dried gizzard
      membrane of Gallus gallus domesticus Brisson, was assessed for its effects and
      mechanism on urolithiasis. AIMS OF STUDY: To evaluate the effects of ECGG extract
      on calcium oxalate (CaOx) crystal formation in vitro, and assess the anti
      urolithic effects of ECGG extract in vivo and explore the underlying mechanism.
      MATERIALS AND METHODS: In vitro, CaOx crystals were treated with ECGG extract
      (0.05, 0.2, and 0.8 g/mL), and assessed by scanning electron microscopy, Fourier
      transform infrared spectroscopy, X-ray powder diffraction and electrical
      conductivity. Then, a rat model of renal calculi was established by ethylene
      glycol and ammonium chloride treatment, and ECGG extract (5.0, 10.0 and 20.0
      g/kg) was administered orally. After treatment, urine, serum and kidney
      bioindicators were analyzed, as well as kidney's pathological features. RESULTS:
      In the presence of ECGG extract, calcium oxalate dihydrate (COD) crystals with
      typical tetragonal bipyramidal morphology were obtained; meanwhile, the formation
      of calcium oxalate monohydrate (COM), a major urinary stone component, was
      inhibited; in addition, the equilibration time of the chemical reaction of Ca2+
      and C2O42- ions was delayed in a concentration dependent manner. ECGG extract
      actually showed anti-urolithic effects; the incidence rates of crystal formation
      in the kidney in the model, low, middle and high dose groups were 100%, 90%, 70%
      and 60%, respectively, with a dose-dependent alleviation of kidney stone amounts
      and kidney damage. Treatment with middle and high ECGG extract doses
      significantly decreased urine uric acid and oxalic acid amounts, serum
      creatinine, urea nitrogen and uric acid contents, and kidney tissue oxalic acid
      and calcium levels, while increasing kidney and urinary magnesium and superoxide
      dismutase levels (P < 0.05). CONCLUSION: ECGG extract has outstanding anti
      urolithic effects, potentially with included bioorganic molecules inducing COD
      crystal nucleation and growth. Therefore, ECGG extract is a promising drug for
      preventing and treating urolithiasis.

PMID- 30194057
TI  - Stress and cell cycle regulation during somatic embryogenesis plays a key role in
      oil palm callus development.
AB  - : Oil palm is an oleaginous plant of relevant economic importance since its
      fruits are rich in vegetable oil. These plants have a single apical meristem and
      the main method for vegetative propagation is somatic embryogenesis. The aim of
      this study was to identify differentially abundant proteins from oil palm
      genotypes contrasting in the capacity of embryogenic competence acquisition,
      using shotgun proteomics. Oil palm leaves were subjected to callus induction and
      the material was collected in biological triplicates at 14 and 90 days of callus
      induction. LC-MS/MS analysis was performed and revealed a total of 4695 proteins.
      Responsive and non-responsive genotypes were compared at 14 and 90 days of callus
      induction and 221 differentially abundant proteins were obtained. The data
      analysis revealed several proteins mainly related to energy metabolism, stress
      response and regulation of cell cycle, further analyzed by qRT-PCR, which seem
      important for embryogenic development. We suggest some of these proteins as key
      factors for the success of callus formation in oil palm including antioxidant and
      cell division proteins as well as proteins involved in the ubiquitination
      pathway. These proteins may also be potential biomarkers for the acquisition of
      embryogenic competence. SIGNIFICANCE: Antioxidant and cell division proteins as
      well as proteins involved in the ubiquitination pathway are key factors for the
      success of callus formation in oil palm. The proteins identified in this study
      may be potential biomarkers for embryogenic competence acquisition.

PMID- 30194058
TI  - Clinical Decision Support Systems for Drug Allergy Checking: Systematic Review.
AB  - BACKGROUND: Worldwide, the burden of allergies-in particular, drug allergies-is
      growing. In the process of prescribing, dispensing, or administering a drug, a
      medication error may occur and can have adverse consequences; for example, a drug
      may be given to a patient with a documented allergy to that particular drug.
      Computerized physician order entry (CPOE) systems with built-in clinical decision
      support systems (CDSS) have the potential to prevent such medication errors and
      adverse events. OBJECTIVE: The aim of this review is to provide a comprehensive
      overview regarding all aspects of CDSS for drug allergy, including documenting,
      coding, rule bases, alerts and alert fatigue, and outcome evaluation. METHODS:
      The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)
      guidelines were followed as much as possible and searches were conducted in 5
      databases using CPOE, CDSS, alerts, and allergic or allergy as keywords. Bias
      could not be evaluated according to PRISMA guidelines due to the heterogeneity of
      study types included in the review. RESULTS: Of the 3160 articles considered, 60
      met the inclusion criteria. A further 9 articles were added based on expert
      opinion, resulting in a total of 69 articles. An interrater agreement of 90.9%
      with a reliability Kappa=.787 (95% CI 0.686-0.888) was reached. Large
      heterogeneity across study objectives, study designs, study populations, and
      reported results was found. Several key findings were identified. Evidence of the
      usefulness of clinical decision support for drug allergies has been documented.
      Nevertheless, there are some important problems associated with their use.
      Accurate and structured documenting of information on drug allergies in
      electronic health records (EHRs) is difficult, as it is often not clear to
      healthcare providers how and where to document drug allergies. Besides the
      underreporting of drug allergies, outdated or inaccurate drug allergy information
      in EHRs poses an important problem. Research on the use of coding terminologies
      for documenting drug allergies is sparse. There is no generally accepted standard
      terminology for structured documentation of allergy information. The final key
      finding is the consistently reported low specificity of drug allergy alerts.
      Current systems have high alert override rates of up to 90%, leading to alert
      fatigue. Important challenges remain for increasing the specificity of drug
      allergy alerts. We found only one study specifically reporting outcomes related
      to CDSS for drug allergies. It showed that adverse drug events resulting from
      overridden drug allergy alerts do not occur frequently. CONCLUSIONS: Accurate and
      comprehensive recording of drug allergies is required for good use of CDSS for
      drug allergy screening. We found considerable variation in the way drug allergy
      are recorded in EHRs. It remains difficult to reduce drug allergy alert overload
      while maintaining patient safety as the highest priority. Future research should
      focus on improving alert specificity, thereby reducing override rates and alert
      fatigue. Also, the effect on patient outcomes and cost-effectiveness should be
      evaluated.

PMID- 30194059
TI  - A Dietary Assessment App for Hospitalized Patients at Nutritional Risk:
      Development and Evaluation of the MyFood App.
AB  - BACKGROUND: Disease-related malnutrition is a common challenge among hospitalized
      patients. There seems to be a lack of an effective system to follow-up
      nutritional monitoring and treatment of patients at nutritional risk after risk
      assessment. We identify a need for a more standardized system to prevent and
      treat disease-related malnutrition. OBJECTIVE: We aimed to develop a dietary
      assessment app for tablets for use in a hospital setting and to evaluate the
      app's ability to measure individual intake of energy, protein, liquid, and food
      and beverage items among hospitalized patients for two days. We also aimed to
      measure patients' experiences using the app. METHODS: We have developed the
      MyFood app, which consists of three modules: 1) collection of information about
      the patient, 2) dietary assessment function, and 3) evaluation of recorded intake
      compared to individual needs. We used observations from digital photography of
      the meals, combined with partial weighing of the meal components, as a reference
      method to evaluate the app's dietary assessment system for two days. Differences
      in the intake estimations of energy, protein, liquid, and food and beverage items
      between MyFood and the photograph method were analyzed on both group and
      individual level. RESULTS: Thirty-two patients hospitalized at Oslo University
      Hospital were included in the study. The data collection period ran from March to
      May 2017. About half of the patients had >=90% agreement between MyFood and the
      photograph method for energy, protein, and liquid intake on both recording days.
      Dinner was the meal with the lowest percent agreement between methods. MyFood
      overestimated patients' intake of bread and cereals and underestimated fruit
      consumption. Agreement between methods increased from day 1 to day 2 for bread
      and cereals, spreads, egg, yogurt, soup, hot dishes, and desserts. Ninety percent
      of participants reported that MyFood was easy to use, and 97% found the app easy
      to navigate. CONCLUSIONS: We developed the MyFood app as a tool to monitor
      dietary intake among hospitalized patients at nutritional risk. The recorded
      intake of energy, protein, and liquid using MyFood showed good agreement with the
      photograph method for the majority of participants. The app's ability to estimate
      intake within food groups was good, except for bread and cereals which were
      overestimated and fruits which were underestimated. The app was well accepted
      among study participants and has the potential to be a dietary assessment tool
      for use among patients in clinical practice.

PMID- 30194061
TI  - Ewing Sarcoma Gene Fusions Can Be Generated via Chromoplexy.
AB  - EWSR1-ETS fusions can arise by a sudden burst of complex, loop-like
      rearrangements termed chromoplexy.

PMID- 30194060
TI  - A Mobile Health Intervention for HIV Prevention Among Racially and Ethnically
      Diverse Young Men: Usability Evaluation.
AB  - BACKGROUND: Mobile health (mHealth) apps have the potential to be a useful mode
      of delivering HIV prevention information, particularly for young men (13-24
      years) who account for 21% of new HIV diagnoses in the United States. We
      translated an existing evidence-based, face-to-face HIV prevention curriculum
      into a portable platform and developed a mobile Web app: MyPEEPS Mobile.
      OBJECTIVE: The purpose of this study was to assess the usability of MyPEEPS
      Mobile from both expert and end user perspectives. METHODS: We conducted a
      heuristic evaluation with five experts in informatics to identify violations of
      usability principles and end user usability testing with 20 young men aged 15 to
      18 years in New York, NY, Birmingham, AL, and Chicago, IL to identify potential
      obstacles to their use of the app. RESULTS: Mean scores of the overall severity
      of the identified heuristic violations rated by experts ranged from 0.4 and 2.6
      (0=no usability problem to 4=usability catastrophe). Overall, our end users
      successfully completed the tasks associated with use case scenarios and provided
      comments/recommendations on improving usability of MyPEEPS Mobile. The mean of
      the overall Post-Study System Usability Questionnaire scores rated by the end
      users was 1.63 (SD 0.65), reflecting strong user acceptance of the app.
      CONCLUSIONS: The comments made by experts and end users will be used to refine
      MyPEEPS Mobile prior to a pilot study assessing the acceptability of the app
      across diverse sexual minority young men in their everyday lives.

PMID- 30194062
TI  - Mutations and Targeted Drugs Alter RAS Signaling Dynamics in Cancer.
AB  - Oncogenic mutations and targeted drugs promote slow deactivation of activated RAS
      signaling.

PMID- 30194063
TI  - The lnCRNA NORAD Contributes to the Maintenance of Genomic Stability.
AB  - NORAD binds to RBMX to facilitate the assembly of a topoisomerase I complex
      termed NARC1.

PMID- 30194064
TI  - Capmatinib plus Gefitinib Is Active in EGFR-Mutant MET-Amplified Tumors.
AB  - Capmatinib plus gefitinib had a 27% to 29% response rate in patients who
      progressed on prior EGFR TKI therapy.

PMID- 30194065
TI  - New NHS app will let patients book GP appointments on mobiles.

PMID- 30194066
TI  - Seven days in medicine: 29 August to 4 September 2018.

PMID- 30194067
TI  - US hospitals launch non-profit generic drug producer to counter rising prices.

PMID- 30194069
TI  - Specific Targeting of Oncogenes Using CRISPR Technology.
AB  - In recent decades, tools of molecular biology have enabled researchers to
      genetically modify model organisms, including human cells. RNAi, zinc-finger
      nucleases, transcription activator-like effector nucleases, CRISPR-Cas9
      (clustered regularly-interspaced short palindromic repeats and CRISPR-associated
      protein 9), retro- or lentiviral gene transfer, and many other methods can be
      utilized to remove genes, add genes, or change their expression. Within the same
      timeframe, survival rates for many highly malignant tumor diseases have not
      improved substantially. If modern medicine could apply even a subset of research
      methods in clinical management, which are already well established and
      controllable in basic research laboratories, this could strongly impact patients'
      prognosis. CRISPR-Cas9 is a method to precisely target and manipulate genomic
      loci and recent studies have attempted to use this method as a genetic treatment
      for Duchenne muscular dystrophy, blood disorders, autosomal-dominant hearing
      loss, and cancer. Some of these approaches target mutant genomic sequences
      specifically and try to avoid affecting the respective normal loci. Considering
      obvious genetic risks opposing the objected benefits, data are needed to show
      whether CRISPR technology is suitable as a future cancer therapy approach or not.
      Here, we develop strategies for the specific targeting of viral cancer drivers
      and oncogenes activated by mutation, using the latest CRISPR technology. Cancer
      Res; 78(19); 5506-12. (c)2018 AACR.

PMID- 30194070
TI  - Correction: Towards evidence-based emergency medicine: best BETs from the
      Manchester Royal Infirmary.

PMID- 30194068
TI  - Low-Molecular-Weight Cyclin E in Human Cancer: Cellular Consequences and
      Opportunities for Targeted Therapies.
AB  - Cyclin E, a regulatory subunit of cyclin-dependent kinase 2 (CDK2), is central to
      the initiation of DNA replication at the G1/S checkpoint. Tight temporal control
      of cyclin E is essential to the coordination of cell-cycle processes and the
      maintenance of genome integrity. Overexpression of cyclin E in human tumors was
      first observed in the 1990s and led to the identification of oncogenic roles for
      deregulated cyclin E in experimental models. A decade later, low-molecular-weight
      cyclin E (LMW-E) isoforms were observed in aggressive tumor subtypes. Compared
      with full-length cyclin E, LMW-E hyperactivates CDK2 through increased complex
      stability and resistance to the endogenous inhibitors p21CIP1 and p27KIP1 LMW-E
      is predominantly generated by neutrophil elastase-mediated proteolytic cleavage,
      which eliminates the N-terminal cyclin E nuclear localization signal and promotes
      cyclin E's accumulation in the cytoplasm. Compared with full-length cyclin E, the
      aberrant localization and unique stereochemistry of LMW-E dramatically alters the
      substrate specificity and selectivity of CDK2, increasing tumorigenicity in
      experimental models. Cytoplasmic LMW-E, which can be assessed by IHC, is
      prognostic of poor survival and predicts resistance to standard therapies in
      patients with cancer. These patients may benefit from therapeutic modalities
      targeting the altered biochemistry of LMW-E or its associated vulnerabilities.
      Cancer Res; 78(19); 5481-91. (c)2018 AACR.

PMID- 30194071
TI  - Evidence that therapeutic hypothermia should be continued for 72 hours.

PMID- 30194072
TI  - Caenorhabditis elegans ced-3 Caspase Is Required for Asymmetric Divisions That
      Generate Cells Programmed To Die.
AB  - Caspases have functions other than in apoptosis. Here, we report that
      Caenorhabditis elegans CED-3 caspase regulates asymmetric cell division. Many of
      the 131 cells that are "programmed" to die during C. elegans development are the
      smaller daughter of a neuroblast that divides asymmetrically by size and fate. We
      have previously shown that CED-3 caspase is activated in such neuroblasts, and
      that before neuroblast division, a gradient of CED-3 caspase activity is formed
      in a ced-1 MEGF10 ( m ultiple EGF -like domains 10 )-dependent manner. This
      results in the nonrandom segregation of active CED-3 caspase or "apoptotic
      potential" into the smaller daughter. We now show that CED-3 caspase is necessary
      for the ability of neuroblasts to divide asymmetrically by size. In addition, we
      provide evidence that a pig-1 MELK (maternal embryonic leucine zipper kinase)
      dependent reciprocal gradient of "mitotic potential" is formed in the QL.p
      neuroblast, and that CED-3 caspase antagonizes this mitotic potential. Based on
      these findings, we propose that CED-3 caspase plays a critical role in the
      asymmetric division by size and fate of neuroblasts, and that this contributes to
      the reproducibility and robustness with which the smaller daughter cell is
      produced and adopts the apoptotic fate. Finally, the function of CED-3 caspase in
      this context is dependent on its activation through the conserved egl-1 BH3-only,
      ced-9 Bcl-2, and ced-4 Apaf-1 pathway. In mammals, caspases affect various
      aspects of stem cell lineages. We speculate that the new nonapoptotic function of
      C. elegans CED-3 caspase in asymmetric neuroblast division is relevant to the
      function(s) of mammalian caspases in stem cells.

PMID- 30194074
TI  - MERTK Promotes Resistance to Irreversible EGFR Tyrosine Kinase Inhibitors in Non
      small Cell Lung Cancers Expressing Wild-type EGFR Family Members.
AB  - Purpose: Lung cancer is the leading cause of cancer-related death. Non-small cell
      lung cancer (NSCLC) accounts for 85% of all lung cancers and over 60% express
      wild-type EGFR (wtEGFR); however, EGFR tyrosine kinase inhibitors (TKIs) have
      limited effect in most patients with wtEGFR tumors. We previously identified
      MERTK tyrosine kinase as a potential therapeutic target in NSCLC and developed
      MRX-2843, a novel MERTK-selective inhibitor with favorable properties for
      clinical translation. The goal of this study was to determine whether MERTK and
      EGFR inhibitor combination therapy could provide antitumor efficacy against
      wtEGFR NSCLC.Experimental Design: An unbiased screen of 378 kinase inhibitors was
      conducted to identify synergistic interactions with MRX-2843 and biochemical and
      therapeutic effects were determined in vitro and in vivo Results: Numerous
      irreversible EGFR TKIs, including CO-1686 and osimertinib, synergized with MRX
      2843 to inhibit wtEGFR NSCLC cell expansion, irrespective of driver oncogene
      status. CO-1686 and MRX-2843 combination therapy inhibited MERTK, wtEGFR, and
      ERBB2/ERBB3 and decreased downstream PI3K-AKT, MAPK-ERK, and AURORA kinase (AURK)
      signaling more effectively than single agents. Inhibition of PI3K, AKT or AURK,
      but not MEK, synergized with CO-1686 to inhibit tumor cell expansion, suggesting
      their roles as key redundant resistance pathways. Treatment with MRX-2843 and CO
      1686 or osimertinib prevented xenograft growth while single agents had limited
      effect. Tumor growth inhibition was durable even after treatment with combination
      therapy was stopped.Conclusions: Our data support the application of MRX-2843 in
      combination with an irreversible EGFR TKI as a novel strategy for treatment of
      patients with wtEGFR NSCLC. Clin Cancer Res; 1-13. (c)2018 AACR.

PMID- 30194073
TI  - Selection and Plasmid Transfer Underlie Adaptive Mutation in Escherichia coli.
AB  - In the Cairns-Foster adaptive mutation system, a +1 lac frameshift mutant of
      Escherichia coli is plated on lactose medium, where the nondividing population
      gives rise to Lac+ revertant colonies during a week under selection. Reversion
      requires the mutant lac allele to be located on a conjugative F'lac plasmid that
      also encodes the error-prone DNA polymerase, DinB. Rare plated cells with
      multiple copies of the mutant F'lac plasmid initiate the clones that develop into
      revertants under selection. These initiator cells arise before plating, and their
      extra lac copies allow them to divide on lactose and produce identical F'lac
      bearing daughter cells that can mate with each other. DNA breaks can form during
      plasmid transfer and their recombinational repair can initiate rolling-circle
      replication of the recipient plasmid. This replication is mutagenic because the
      amplified plasmid encodes the error-prone DinB polymerase. A new model proposes
      that Lac+ revertants arise during mutagenic over-replication of the F'lac plasmid
      under selection. This mutagenesis is focused on the plasmid because the cell
      chromosome replicates very little. The outer membrane protein OmpA is essential
      for reversion under selection. OmpA helps cells conserve energy and may stabilize
      the long-term mating pairs that produce revertants.

PMID- 30194075
TI  - Developing tools to enhance the use of systematic reviews for clinical care in
      health systems.
AB  - We aimed to develop tools that can facilitate uptake of evidence summarised in
      systematic reviews by clinical decision makers in health systems. After
      conducting a systematic review on the management of anxiety in children, we
      interviewed health system representatives, clinicians and patients to ask about
      additional information needed for decision-making. Using stakeholders' feedback
      and literature searches for contextual and implementation information, we
      developed two tools (decision aids (DAs)), one for the health system and the
      second for the clinical encounter. This information mapped to factors of the
      GRADE (Grading of Recommendations, Assessment, Development and Evaluation)
      Evidence to Decision Framework. The health system DAs provided information on
      which patients are candidate for treatment, values and preferences, costs and
      resources, acceptability, impact on health equity, feasibility, drug dosing,
      alternative therapies, remission rates and prognosis. Health system stakeholders
      found the DA useful for clinical decision-making and generalisable to other
      conditions. The encounter DA was produced as cards containing information on
      issues that drive treatment decisions (effect on symptoms, effect on function,
      treatment burden, side effects and cost). Patients and parents prioritised the
      cards and chose the order in which these issues were discussed with clinician.
      The encounter DA was found to be helpful by patients, parents and clinicians. We
      conclude that the uptake of evidence summaries by health systems can be enhanced
      by developing tools that provide contextual and implementation information about
      clinical care. A dual approach addressing health system stakeholders as well as
      clinicians and patients is likely feasible and helpful.

PMID- 30194076
TI  - Whole-transcriptomic Profile of SK-MEL-3 Melanoma Cells Treated with the Histone
      Deacetylase Inhibitor: Trichostatin A.
AB  - BACKGROUND: Malignant melanoma cells can rapidly acquire phenotypic properties
      making them resistant to radiation and mainline chemotherapies such as
      decarbonize or kinase inhibitors that target RAS-proto-oncogene independent auto
      activated mitogen-activated protein kinases (MAPK)/through dual specificity
      mitogen-activated protein kinase (MEK). Both drug resistance and inherent
      transition from melanocytic nevi to malignant melanoma involve the overexpression
      of histone deacetylases (HDACs) and a B-Raf proto-oncogene (BRAF) mutation.
      MATERIALS AND METHODS: In this work, the effects of an HDAC class I and II
      inhibitor trichostatin A (TSA) on the whole transcriptome of SK-MEL-3 cells
      carrying a BRAF mutation was examined. RESULTS: The data obtained show that TSA
      was an extremely potent HDAC inhibitor within SK-MEL-3 nuclear lysates, where TSA
      was then optimized for appropriate sub-lethal concentrations for in vitro
      testing. The whole-transcriptome profile shows a basic phenotype dominance in the
      SK-MEL-3 cell line for i) synthesis of melanin, ii) phagosome acidification, iii)
      ATP hydrolysis-coupled proton pumps and iv) iron transport systems. While TSA did
      not affect the aforementioned major systems, it evoked a dramatic change to the
      transcriptome: reflected by a down-regulation of 810 transcripts and up
      regulation of 833, with fold-change from -15.27 to +31.1 FC (p<0.00001). Largest
      differentials were found for the following transcripts: Up-regulated: Tetraspanin
      13 (TSPAN13), serpin family i member 1 (SERPINI1), ATPase Na+/K+ transporting
      subunit beta 2 (ATP1B2), nicotinamide nucleotide adenylyl transferase 2 (NMNAT2),
      platelet-derived growth factor receptor-like (PDGFRL), cytochrome P450 family 1
      subfamily A member 1 (CYP1A1), prostate androgen-regulated mucin-like protein 1
      (PARM1), secretogranin II (SCG2), SYT11 (synaptotagmin 11), rhophilin associated
      tail protein 1 like (ROPN1L); down-regulated: polypeptide N
      acetylgalactosaminyltransferase 3 (GALNT3), carbonic anhydrase 14 (CAXIV), BCL2
      related protein A1 (BCL2A1), protein kinase C delta (PRKCD), transient receptor
      potential cation channel subfamily M member 1 (TRPM1), ubiquitin associated
      protein 1 like (UBAP1L), glutathione peroxidase 8 (GPX8), interleukin 16 (IL16),
      tumor protein p53 (TP53), and serpin family H member 1 (SERPINH1). There was no
      change to any of the HDAC transcripts (class I, II and IV), the sirtuin HDAC
      family (1-6) or the BRAF proto-oncogene v 599 transcripts. However, the data
      showed that TSA down-regulated influential transcripts that drive the BRAF
      extracellular signal-regulated kinase (ERK)1/2 oncogenic pathway (namely PRKCD
      and MYC proto-oncogene which negatively affected the cell-cycle distribution.
      Mitotic inhibition was corroborated by functional pathway analysis and flow
      cytometry confirming halt at the G2 phase, occurring in the absence of toxicity.
      CONCLUSION: TSA does not alter HDAC transcripts nor BRAF itself, but down
      regulates critical components of the MAPK/MEK/BRAF oncogenic pathway, initiating
      a mitotic arrest.

PMID- 30194077
TI  - Copy Number Alterations in Tumor Genomes Deleting Antineoplastic Drug Targets
      Partially Compensated by Complementary Amplifications.
AB  - BACKGROUND/AIM: Genomic DNA copy number alterations (CNAs) are frequent in tumors
      and have been catalogued by The Cancer Genome Atlas project. Emergence of
      chemoresistance frequently renders drug therapies ineffective. MATERIALS AND
      METHODS: We analyzed how CNAs recurrently found in the genomes of TCGA patients
      of thirty-one tumor types affect protein targets of antineoplastic (AN) agents.
      RESULTS: CNA deletions more frequently affected the targets of AN agents than CNA
      amplifications. Interestingly, in seven tumors we observed signs of compensatory
      CNAs. For example, in glioblastoma multiforme, two target genes (FLT1, FLT3) of
      the experimental drug sorafenib were recurrently deleted, whereas another target
      (KDR) of sorafenib was recurrently amplified. In renal clear cell carcinoma, the
      target FLT1 of pazopanib, sunitinib, sorafenib, and axitinib was recurrently
      deleted, whereas FLT4 bound by the same drugs, was recurrently amplified.
      CONCLUSION: Deletions of AN target proteins can be compensated by amplification
      of alternative targets.

PMID- 30194078
TI  - Pyrosequencing Analysis of MGMT Promoter Methylation in Meningioma.
AB  - BACKGROUND: Methylation of the O6-methylguanine-DNA methyltransferase (MGMT) gene
      promoter is a well-established predictor of response to the DNA-alkylating agent
      temozolomide in patients with glioblastoma. MATERIALS AND METHODS: Pyrosequencing
      analysis was used to determine the MGMT promoter methylation status in 61
      meningiomas, to clarify whether it might have a predictive role. RESULTS: Only
      two tumors (3%) had a mean methylation frequency higher than the cut-off value of
      10% for the four CpG sites examined. CONCLUSION: The methylation of the MGMT
      promoter is uncommon, or occurs at a low frequency in meningiomas. There is no
      convincing rationale to test such tumors for their MGMT methylation status in a
      clinical setting.

PMID- 30194079
TI  - Expression of the Vesicular Monoamine Transporter Gene Solute Carrier Family 18
      Member 1 (SLC18A1) in Lung Cancer.
AB  - BACKGROUND: One aspect of smoking and lung cancer that has not been closely
      examined, is that regarding genes that may predispose to tobacco dependence.
      Smoking and mental illness are tightly linked, apparently the result of smokers
      using cigarettes to self-medicate for mental problems. The gene for solute
      carrier family 18 member A1 (vesicular monoamine transporter; SLC18A1) is of
      particular interest in this regard because of its association with schizophrenia,
      autism and bipolar illness as well as with cancer. In the current study, the
      relationship of SLC18A1 expression with smoking and lung cancer was analyzed.
      MATERIALS AND METHODS: The association between smoking, SLC18A1 expression and
      overall survival in the lung cancer dataset in The Cancer Genome Atlas was
      evaluated using the Genomic Data Commons Data Portal
      (https://portal.gdc.cancer.gov), as well as CbioPortal for Cancer Genomics
      (http://www.cbioportal.org) and the University of California Santa Cruz Xena
      browser (https://xenabrowser.net). RESULTS: Increased expression of SLC18A1 was
      found to be associated with a significantly increased survival in patients with
      adenocarcinoma (p=0.0058), but not those with squamous carcinoma (p=0.96).
      Lifelong never-smokers had the highest SLC18A1 expression. In the Pan Cancer
      Atlas, increased expression of SLC18A1 places such a tumor in group C5, among
      immunologically-quiet tumors. CONCLUSION: Most never-smokers with lung cancer do
      not respond to immune checkpoint inhibitors (ICIs). But for unknown reasons, a
      small proportion do show clinical benefit from the ICI pembrolizumab. Because of
      the good response of this group, it may be worthwhile assessing their SLC18A1
      expression pre-treatment as a marker for potential clinical benefit. If SLC18A1
      expression is low, a never-smoker may respond well to ICIs. High levels of
      expression would indicate a C5 tumor less likely to respond to ICIs. SLC18A1
      might complement other biomarkers currently under study in relation to programmed
      cell death protein 1/programmed cell death protein ligand 1 inhibition.

PMID- 30194080
TI  - Pull-down Assay on Streptavidin Beads and Surface Plasmon Resonance Chips for
      SWATH-MS-based Interactomics.
AB  - BACKGROUND/AIM: Pul-down assay is a popular in vitro method for identification of
      physical interactors of selected proteins. Here, for the first time, we compared
      three conventional variants of pull-down assay with the streptavidin-modified
      surface plasmon resonance (SPR) chips for the detection of PDZ and LIM domain
      protein 2 (PDLIM2) interaction partners. MATERIALS AND METHODS: PDLIM2 protein
      protein interactions were analysed by three variants of pull-down assay on
      streptavidin beads using LC-MS/MS in "Sequential Window Acquisition of all
      Theoretical fragment ion spectra (SWATH)" mode and compared with LC-SWATH-MS/MS
      data from SPR chips. RESULTS: The results showed that (i) the use of SPR chip led
      to comparable data compared to on-column streptavidin beads, (ii) gravity flow
      and microflow in wash and elution steps provided better results than
      centrifugation, and (iii) type and concentration of detergent did not
      significantly affect the interactome data of cancer-associated PDLIM2.
      CONCLUSION: Our study supports further application of SPR-based affinity
      purification with SWATH mass spectrometry for reproducible and controlled
      characterization of cancer-associated interactomes.

PMID- 30194081
TI  - Contribution of Murine Double Minute 2 Genotypes to Colorectal Cancer Risk in
      Taiwan.
AB  - BACKGROUND/AIM: The genomic role of human mouse double minute 2 (MDM2) in
      colorectal cancer (CRC) is unclear, therefore, our study aimed to evaluate the
      contribution of MDM2 genotype to the risk of CRC in Taiwan. MATERIALS AND
      METHODS: In this case-control study, MDM2 SNP309 T to G (rs2279744) genotypes
      were determined and their association with CRC risk were investigated among 362
      patients with CRC and 362 age- and gender-matched healthy controls in central
      Taiwan. In addition, the interaction of MDM2 SNP309 genotypes with personal
      behaviors and clinicopathological features were also examined. RESULTS: The
      percentage of variant GG for the MDM2 SNP309 genotype was 30.9% in the CRC group
      and 24.0% in the control group, respectively (odds ratio (OR)=1.78, 95%
      confidence interval (CI)=1.25-2.86, p=0.0057). The allelic frequency distribution
      analysis showed that the variant G allele of MDM2 SNP309 conferred a
      significantly increased susceptibility to CRC compared with the wild-type T
      allele (OR=1.32, 95% CI=1.14-1.69, p=0.0062). As for the gene-lifestyle
      interaction, there was an obvious joint effect of MDM2 SNP309 GG genotype on the
      risk of CRC among ever-smokers and non-alcohol drinkers, but not non-smoker or
      alcohol drinker subgroups. No statistically significant correlation was observed
      between MDM2 SNP309 genotypic distributions and age, gender, tumor size, location
      or metastasis status. CONCLUSION: The genotypes of MDM2 SNP309 may allow forr
      early detection of and predictor for CRC risk, especially among smokers and non
      alcohol drinkers, but not for prognosis. The combined effects of MDM2 SNP309 and
      other genes (such as matrix metalloproteinases) on CRC susceptibility and
      prognosis, should also be taken into consideration in the era of precision
      medicine.

PMID- 30194082
TI  - Indirect Down-regulation of Tumor-suppressive let-7 Family MicroRNAs by LMO1 in
      Neuroblastoma.
AB  - BACKGROUND/AIM: Overall survival for the high-risk group of neuroblastoma (NB)
      patients still remains at 40-50%, necessitating the establishment of a curable
      treatment. LIM domain only 1 (LMO1) gene encoding a transcriptional regulator is
      an NB-susceptibility gene with a tumor-promoting activity. Previously we
      conducted chromatin immunoprecipitation and DNA sequencing analyses on NB cell
      lines and identified 3 protein-coding genes regulated by LMO1. In this study, we
      extended our analyses to capture microRNA genes directly or indirectly regulated
      by LMO1. MATERIALS AND METHODS: Using microarrays, we conducted a comparative
      gene expression analysis on an NB cell line SK-N-SH; between the cells with and
      without LMO1 suppression. RESULTS: Overall, 18 microRNAs were identified to be
      indirectly down-regulated by LMO1 including 7 microRNAs of the let-7 family,
      whose cell proliferation inhibitory activity was observed. CONCLUSION: Target
      genes of the LMO1-regulated microRNAs and their relevant pathways may be a
      potential therapeutic target.

PMID- 30194084
TI  - Successful Treatment of HIV-Associated Kaposi Sarcoma with Immune Checkpoint
      Blockade.
AB  - Kaposi sarcoma (KS) is an incurable, human immunodeficiency virus (HIV)
      associated malignancy. We reviewed 320 immunotherapy-treated patient records.
      Seventeen had HIV-associated malignancies, including nine men with KS. Median
      viral load was 20 copies/mL (range, undetectable to 549,704) and median CD4 count
      was 256 cells/MUL (range, 10-603). Eight patients received nivolumab and one
      received pembrolizumab. Six patients (67%) achieved partial (N = 5) or complete
      remission (N = 1). No drug-related grade >2 toxicities occurred. In seven
      patients, CD4 counts increased (P = 0.09). Tissue and/or blood-derived
      circulating tumor DNA (ctDNA) was evaluated by next-generation sequencing. Four
      evaluable patients each showed anomalies in distinct genes: TP53, KRAS, TLL2,
      PTPN6 (tissue and/or ctDNA), and NF1 (ctDNA). Tumor mutational burden was low,
      and PD-L1 immunohistochemistry was negative (three and four assessable patients,
      respectively). Responders included patients with low CD4 counts, high HIV load,
      and/or visceral disease. In summary, checkpoint blockade demonstrated significant
      antitumor activity and low toxicity in patients with HIV-associated KS. Cancer
      Immunol Res; 6(10); 1129-35. (c)2018 AACR.

PMID- 30194085
TI  - High exposure to nicotine among adolescents who use Juul and other vape pod
      systems ('pods').

PMID- 30194083
TI  - Bridging Cancer Biology with the Clinic: Comprehending and Exploiting IDH Gene
      Mutations in Gliomas.
AB  - Isocitrate dehydrogenases 1 and 2 (IDH1/2) are enzymes that play a major role in
      the Krebs cycle. Mutations in these enzymes are found in the majority of lower
      gliomas and secondary glioblastomas, but also in myeloid malignancies and other
      cancers. IDH1 and IDH2 mutations are restricted to specific arginine residues in
      the active site of the enzymes and are gain-of-function, i.e. they confer a
      neomorphic enzyme activity resulting in the accumulation of D-2-hydroxyglutarate
      (2-HG). 2-HG is an oncometabolite causing profound metabolic dysregulation which,
      among others, results in methylator phenotypes and in defects in homologous
      recombination repair. In this review, we summarize current knowledge regarding
      the function of normal and mutated IDH, explain the possible mechanisms through
      which these mutations might drive malignant transformation of progenitor cells in
      the central nervous system, and provide a comprehensive review of potential
      treatment strategies for IDH-mutated malignancies, focusing on gliomas.

PMID- 30194086
TI  - Long-read sequencing identified intronic repeat expansions in SAMD12 from Chinese
      pedigrees affected with familial cortical myoclonic tremor with epilepsy.
AB  - BACKGROUND: The locus for familial cortical myoclonic tremor with epilepsy
      (FCMTE) has long been mapped to 8q24 in linkage studies, but the causative
      mutations remain unclear. Recently, expansions of intronic TTTCA and TTTTA repeat
      motifs within SAMD12 were found to be involved in the pathogenesis of FCMTE in
      Japanese pedigrees. We aim to identify the causative mutations of FCMTE in
      Chinese pedigrees. METHODS: We performed genetic linkage analysis by
      microsatellite markers in a five-generation Chinese pedigree with 55 members. We
      also used array-comparative genomic hybridisation (CGH) and next-generation
      sequencing (NGS) technologies (whole-exome sequencing, capture region deep
      sequencing and whole-genome sequencing) to identify the causative mutations in
      the disease locus. Recently, we used low-coverage (~10*) long-read genome
      sequencing (LRS) on the PacBio Sequel and Oxford Nanopore platforms to identify
      the causative mutations, and used repeat-primed PCR for validation of the repeat
      expansions. RESULTS: Linkage analysis mapped the disease locus to 8q23.3-24.23.
      Array-CGH and NGS failed to identify causative mutations in this locus. LRS
      identified the intronic TTTCA and TTTTA repeat expansions in SAMD12 as the
      causative mutations, thus corroborating the recently published results in
      Japanese pedigrees. CONCLUSIONS: We identified the pentanucleotide repeat
      expansion in SAMD12 as the causative mutation in Chinese FCMTE pedigrees. Our
      study also suggested that LRS is an effective tool for molecular diagnosis of
      genetic disorders, especially for neurological diseases that cannot be positively
      diagnosed by conventional clinical microarray and NGS technologies.

PMID- 30194087
TI  - The impact of PI 5-phosphatases on phosphoinositides in cell function and human
      disease.
AB  - Phosphoinositides (PIs) are recognized as major signaling molecules in many
      different functions of eukaryotic cells. PIs can be dephosphorylated by multiple
      phosphatase activities at the 5-, 4- and 3- positions. Human PI 5-phosphatases
      belong to a family of 10 members. Except for INPP5A, they all catalyze the
      dephosphorylation of PI(4,5)P2 and/or PI(3,4,5)P3 at the 5- position. PI 5
      phosphatases thus directly control the levels of PI(3,4,5)P3 and also participate
      in fine-tuning regulatory mechanisms of PI(3,4)P2 and PI(4,5)P2. Second messenger
      functions have been demonstrated for PI(3,4)P2 in invadopodium maturation and in
      lamellipodia formation. PI 5-phosphatases can use several substrates on isolated
      enzymes, and it has been challenging to establish their real substrate in vivo.
      PI(4,5)P2 has multiple functions in signaling, including interaction with
      scaffold proteins, ion channels, and cytoskeleton proteins. PI 5-phosphatase
      isoenzymes have been individually implicated in human diseases, such as the
      oculocerebrorenal syndrome of Lowe, through mechanisms which include lipid
      controlling. Oncogenic and tumor suppressive functions of PI 5-phosphatases have
      also been reported in different cell contexts. The mechanisms responsible for
      genetic diseases and for tumor suppressor or oncogenic functions are not fully
      understood. The regulation of PI 5-phosphatases is thus crucial in understanding
      cell functions.

PMID- 30194088
TI  - Barriers and motivators towards a national final year assessment in the United
      Kingdom and the Republic of Ireland for veterinary undergraduates.
AB  - In the final year of the course schools assess students to ensure a minimum level
      of knowledge and skills is achieved before graduation as a veterinary surgeon.
      Across the universities, different styles and combinations of assessments are
      used. A national assessment could provide a solution to maintain quality and
      potential employability of veterinary surgeons. The aim of this study was to
      identify barriers and motivators of veterinary educators from all veterinary
      schools in the UK and the Republic of Ireland towards a national assessment.
      Semistructured interviews were conducted with 16 academic staff members. Mixed
      opinions were expressed and many barriers as well as motivators were voiced. Four
      main themes were: harmonisation and benchmarking, confidence in quality,
      practical feasibility and stakeholder perspectives. The study identified a
      positive attitude towards a national assessment, particularly around improved
      quality and standards. However, the practical feasibility was perceived as a
      significant barrier for implementation. Before making changes to current
      assessments it is important to further research the barriers identified to
      confirm representativeness and to acquire evidence to accept or refute the
      perceived limitations.

PMID- 30194089
TI  - Genomic Prediction Using Multi-trait Weighted GBLUP Accounting for Heterogeneous
      Variances and Covariances Across the Genome.
AB  - Implicit assumption of common (co)variance for all loci in multi-trait Genomic
      Best Linear Unbiased Prediction (GBLUP) results in a genomic relationship matrix
      (G) that is common to all traits. When this assumption is violated, Bayesian
      whole genome regression methods may be superior to GBLUP by accounting for
      unequal (co)variance for all loci or genome regions. This study aimed to develop
      a strategy to improve the accuracy of GBLUP for multi-trait genomic prediction,
      using (co)variance estimates of SNP effects from Bayesian whole genome regression
      methods. Five generations (G1-G5, test populations) of genotype data were
      available by simulations based on data of 2,200 Danish Holstein cows (G0,
      reference population). Two correlated traits with heritabilities of 0.1 or 0.4,
      and a genetic correlation of 0.45 were generated. First, SNP effects and breeding
      values were estimated using BayesAS method, assuming (co)variance was the same
      for SNPs within a genome region, and different between regions. Region size was
      set as one SNP, 100 SNPs, a whole chromosome or whole genome. Second, posterior
      (co)variances of SNP effects were used to weight SNPs in construction of G
      matrices. In general, region size of 100 SNPs led to highest prediction
      accuracies using BayesAS, and wGBLUP outperformed GBLUP at this region size. Our
      results suggest that when genetic architectures of traits favor Bayesian methods,
      the accuracy of multi-trait GBLUP can be as high as the Bayesian method if SNPs
      are weighted by the Bayesian posterior (co)variances.

PMID- 30194090
TI  - Natural Genetic Variation in Yeast Reveals That NEDD4 Is a Conserved Modifier of
      Mutant Polyglutamine Aggregation.
AB  - A feature common to late onset proteinopathic disorders is an accumulation of
      toxic protein conformers and aggregates in affected tissues. In the search for
      potential drug targets, many studies used high-throughput screens to find genes
      that modify the cytotoxicity of misfolded proteins. A complement to this approach
      is to focus on strategies that use protein aggregation as a phenotypic readout to
      identify pathways that control aggregate formation and maintenance. Here we use
      natural variation between strains of budding yeast to genetically map loci that
      influence the aggregation of a polyglutamine-containing protein derived from a
      mutant form of huntingtin, the causative agent in Huntington disease. Linkage
      analysis of progeny derived from a cross between wild and laboratory yeast
      strains revealed two polymorphic loci that modify polyglutamine aggregation. One
      locus contains the gene RFU1 which modifies ubiquitination states of misfolded
      proteins targeted by the E3-ubiquitin ligase complex Rsp5 Activity of the Rsp5
      complex, and the mammalian homolog NEDD4, are critical in maintaining protein
      homeostasis in response to proteomic stress. Our analysis also showed linkage of
      the aggregation phenotype to a distinct locus containing a gene encoding the Rsp5
      interacting Bul2 protein. Allele-swap experiments validated the impact of both
      RFU1 and BUL2 on huntingtin aggregation. Furthermore, we found that the nematode
      Caenorhabditis elegans' ortholog of Rsp5, wwp-1, also negatively regulates
      polyglutamine aggregation. Knockdown of the NEDD4 in human cells likewise altered
      polyglutamine aggregation. Taken together, these results implicate conserved
      processes involving the ubiquitin regulation network that modify protein
      aggregation and provide novel therapeutic targets for polyglutamine and other
      protein folding diseases.

PMID- 30194091
TI  - Discovery of QTL Alleles for Grain Shape in the Japan-MAGIC Rice Population Using
      Haplotype Information.
AB  - A majority of traits are determined by multiple quantitative trait loci (QTL)
      that can have pleiotropic effects. A multi-parent advanced generation inter-cross
      (MAGIC) population is well suited for genetically analyzing the effects of
      multiple QTL on traits of interest because it contains a higher number of QTL
      alleles than a biparental population. We previously produced the JAPAN-MAGIC
      (JAM) population, derived from eight rice (Oryza sativa L.) cultivars with high
      yield and biomass in Japan, and developed the method of genome-wide association
      study (GWAS) using haplotype information on the JAM lines. This method was
      effective for identifying major genes such as Waxy for eating quality and Sd1 for
      culm length. Here, we show that haplotype-based GWAS is also effective for the
      evaluation of multiple QTL with small effects on rice grain shape in the JAM
      lines. Although both the haplotype- and SNP-based GWAS identified multiple QTL
      for grain length and width, the sum of the estimated trait values of each allele
      for the QTL detected by haplotype-based GWAS had higher correlation with observed
      values than those detected by SNP-based GWAS, indicating high-accuracy QTL
      detection in the haplotype-based GWAS. Furthermore, the study revealed
      pleiotropic effects of some QTL regions in regulation of grain shape, suggesting
      that the haplotype-based GWAS using the JAM lines is an effective means to
      evaluate the main and side effects of haplotypes at each QTL. Information on the
      pleiotropic effects of haplotypes on various traits will be useful for designing
      ideal lines in a breeding program.

PMID- 30194092
TI  - Bulked-Segregant Analysis Coupled to Whole Genome Sequencing (BSA-Seq) for Rapid
      Gene Cloning in Maize.
AB  - Forward genetics remains a powerful method for revealing the genes underpinning
      organismal form and function, and for revealing how these genes are tied together
      in gene networks. In maize, forward genetics has been tremendously successful,
      but the size and complexity of the maize genome made identifying mutant genes an
      often arduous process with traditional methods. The next generation sequencing
      revolution has allowed for the gene cloning process to be significantly
      accelerated in many organisms, even when genomes are large and complex. Here, we
      describe a bulked-segregant analysis sequencing (BSA-Seq) protocol for cloning
      mutant genes in maize. Our simple strategy can be used to quickly identify a
      mapping interval and candidate single nucleotide polymorphisms (SNPs) from whole
      genome sequencing of pooled F2 individuals. We employed this strategy to identify
      narrow odd dwarf as an enhancer of teosinte branched1, and to identify a new
      allele of defective kernel1 Our method provides a quick, simple way to clone
      genes in maize.

PMID- 30194093
TI  - Is obstructive sleep apnoea an innocent bystander in the pathophysiology of
      arterial stiffening?

PMID- 30194094
TI  - Resources page.

PMID- 30194095
TI  - Nucleos(t)ide Analogs Do Not Independently Influence Hepatic Fibrosis and Portal
      Hypertension beyond Viral Suppression in CBDL-Induced Cirrhotic Rat.
AB  - Chronic hepatitis is the major cause of liver cirrhosis and portal hypertension.
      Several factors affect portal pressure, including liver fibrosis, splanchnic
      vasodilatation, and pathologic angiogenesis. Nucleos(t)ide analogs (NUCs), the
      oral antiviral agents, effectively attenuate chronic hepatitis B-related liver
      cirrhosis and portal hypertension via viral suppression and alleviation of
      hepatitis. On the other hand, NUCs affect tumor necrosis factor (TNF)-alpha,
      vascular endothelial growth factor (VEGF), and nitric oxide, which participate in
      fibrogenesis, vasodilatation, and angiogenesis. However, whether NUCs
      independently influence liver fibrosis and portal hypertension beyond viral
      suppression is unknown. This study thus aimed to evaluate the influences of three
      frequently used NUCs in rats with nonviral cirrhosis. Male Sprague-Dawley rats
      received common bile duct ligation (CBDL) to induce cholestatic cirrhosis and
      portal hypertension. The rats were randomly allocated into four groups, treated
      by mouth with lamivudine (30 mg/kg per day), entecavir (0.09 mg/kg per day),
      tenofovir (50 mg/kg per day), or distilled water (vehicle control) from the 15th
      day after CBDL. On the 29th day, liver cirrhosis- and portal hypertension-related
      parameters were evaluated. The results showed that chronic NUCs treatment did not
      affect hemodynamic parameters, plasma TNF-alpha concentration, and hepatic
      fibrogenesis protein expressions in rats with nonviral cirrhosis. Though the
      mesenteric VEGF receptor 2 phosphorylation was downregulated in NUCs-treated
      groups, the splanchnic angiogenesis was not influenced. In conclusion,
      lamivudine, entecavir, and tenofovir had no additional effects on liver cirrhosis
      and portal hypertension in rats with nonviral cirrhosis.

PMID- 30194096
TI  - Gene regulation underlies environmental adaptation in house mice.
AB  - Changes in cis-regulatory regions are thought to play a major role in the genetic
      basis of adaptation. However, few studies have linked cis-regulatory variation
      with adaptation in natural populations. Here, using a combination of exome and
      RNA-seq data, we performed expression quantitative trait locus (eQTL) mapping and
      allele-specific expression analyses to study the genetic architecture of
      regulatory variation in wild house mice (Mus musculus domesticus) using
      individuals from five populations collected along a latitudinal cline in eastern
      North America. Mice in this transect showed clinal patterns of variation in
      several traits, including body mass. Mice were larger in more northern latitudes,
      in accordance with Bergmann's rule. We identified 17 genes where cis-eQTLs were
      clinal outliers and for which expression level was correlated with latitude.
      Among these clinal outliers, we identified two genes (Adam17 and Bcat2) with cis
      eQTLs that were associated with adaptive body mass variation and for which
      expression is correlated with body mass both within and between populations.
      Finally, we performed a weighted gene co-expression network analysis (WGCNA) to
      identify expression modules associated with measures of body size variation in
      these mice. These findings demonstrate the power of combining gene expression
      data with scans for selection to identify genes involved in adaptive phenotypic
      evolution, and also provide strong evidence for cis-regulatory elements as
      essential loci of environmental adaptation in natural populations.

PMID- 30194097
TI  - Charles Bonnet syndrome.

PMID- 30194098
TI  - Transcriptional Studies on a Streptomyces clavuligerus oppA2 Deletion Mutant: N
      Acetylglycyl-Clavaminic Acid Is an Intermediate of Clavulanic Acid Biosynthesis.
AB  - The oppA2 gene encodes an oligopeptide-binding protein similar to the periplasmic
      substrate-binding proteins of the ABC transport systems. However, oppA2 is an
      orphan gene, not included in an ABC operon. This gene is located in the
      clavulanic acid (CA) gene cluster of Streptomyces clavuligerus and is essential
      for CA production. A transcriptomic study of the oppA2-null mutant S.
      clavuligerus DeltaoppA2::aac showed changes in the expression levels of 233 genes
      from those in the parental strain. These include genes for ABC transport systems,
      secreted proteins, peptidases, and proteases. Expression of the clavulanic acid,
      clavam, and cephamycin C biosynthesis gene clusters was not significantly
      affected in the oppA2 deletion mutant. The genes for holomycin biosynthesis were
      upregulated 2-fold on average, and the level of upregulation increased to 43-fold
      in a double mutant lacking oppA2 and the pSCL4 plasmid. Strains in which oppA2
      was mutated secreted into the culture the compound N-acetylglycyl-clavaminic acid
      (AGCA), a putative intermediate of CA biosynthesis. A culture broth containing
      AGCA, or AGCA purified by liquid chromatography-mass spectrometry (LC-MS), was
      added to the cultures of various non-CA-producing mutants. Mutants blocked in the
      early steps of the pathway restored CA production, whereas mutants altered in
      late steps did not, establishing that AGCA is a late intermediate of the
      biosynthetic pathway, which is released from the cells when the oligopeptide
      binding protein OppA2 is not available.IMPORTANCE The oppa2 gene encodes an
      oligopeptide permease essential for the production of clavulanic acid. A
      transcriptomic analysis of S. clavuligerus DeltaoppA2::aac in comparison to the
      parental strain S. clavuligerus ATCC 27064 is reported. The lack of OppA2 results
      in different expression of 233 genes, including genes for proteases and genes for
      transport systems. The expression of the clavulanic acid genes in the oppA2
      mutant is not significantly affected, but the genes for holomycin biosynthesis
      are strongly upregulated, in agreement with the higher holomycin production by
      this strain. The oppA2-mutant is known to release N-acetylglycyl-clavaminic acid
      to the broth. Cosynthesis assays using non-clavulanic acid-producing mutants
      showed that the addition of pure N-acetylglycyl-clavaminic acid to mutants in
      which clavulanic acid formation was blocked resulted in the recovery of
      clavulanic acid production, but only in mutants blocked in the early steps of the
      pathway. This suggests that N-acetylglycyl-clavaminic acid is a previously
      unknown late intermediate of the clavulanic acid pathway.

PMID- 30194099
TI  - IdeR, a DtxR Family Iron Response Regulator, Controls Iron Homeostasis,
      Morphological Differentiation, Secondary Metabolism, and the Oxidative Stress
      Response in Streptomyces avermitilis.
AB  - Iron, an essential element for microorganisms, functions as a vital cofactor in a
      wide variety of key metabolic processes. On the other hand, excess iron may have
      toxic effects on bacteria by catalyzing the formation of reactive oxygen species
      through the Fenton reaction. The prevention of iron toxicity requires the precise
      control of intracellular iron levels in bacteria. Mechanisms of iron homeostasis
      in the genus Streptomyces (the producers of various antibiotics) are poorly
      understood. Streptomyces avermitilis is the industrial producer of avermectins,
      which are potent anthelmintic agents widely used in medicine, agriculture, and
      animal husbandry. We investigated the regulatory role of IdeR, a DtxR family
      regulator, in S. avermitilis In the presence of iron, IdeR binds to a specific
      palindromic consensus sequence in promoters and regulates 14 targets involved in
      iron metabolism (e.g., iron acquisition, iron storage, heme metabolism, and Fe-S
      assembly). IdeR also directly regulates 12 targets involved in other biological
      processes, including morphological differentiation, secondary metabolism,
      carbohydrate metabolism, and the tricarboxylic acid (TCA) cycle. ideR
      transcription is positively regulated by the peroxide-sensing transcriptional
      regulator OxyR. A newly constructed ideR deletion mutant (DideR) was found to be
      less responsive to iron levels and more sensitive to H2O2 treatment than the wild
      type strain, indicating that ideR is essential for oxidative stress responses.
      Our findings, taken together, demonstrate that IdeR plays a pleiotropic role in
      the overall coordination of metabolism in Streptomyces spp. in response to iron
      levels.IMPORTANCE Iron is essential to almost all organisms, but in the presence
      of oxygen, iron is both poorly available and potentially toxic. Streptomyces
      species are predominantly present in soil where the environment is complex and
      fluctuating. So far, the mechanism of iron homeostasis in Streptomyces spp.
      remains to be elucidated. Here, we characterized the regulatory role of IdeR in
      the avermectin-producing organism S. avermitilis IdeR maintains intracellular
      iron levels by regulating genes involved in iron absorption and storage. IdeR
      also directly regulates morphological differentiation, secondary metabolism, and
      central metabolism. ideR is under the positive control of OxyR and is
      indispensable for an efficient response to oxidative stress. This investigation
      uncovered that IdeR acts as a global regulator coordinating iron homeostasis,
      morphological differentiation, secondary metabolism, and oxidative stress
      response in Streptomyces species. Elucidation of the pleiotropic regulation
      function of IdeR provides new insights into the mechanisms of how Streptomyces
      spp. adapt to the complex environment.

PMID- 30194100
TI  - Blame it on the metabolite: 3,5-dichloraniline rather than the parent compound is
      responsible for decreasing diversity and function of soil microorganisms.
AB  - Pesticides are key stressors of soil microorganisms with reciprocal effects on
      ecosystem functioning. These effects have been mainly attributed to the parent
      compounds, while the impact of their transformation products (TPs) has been
      largely overlooked. We assessed, in a meadow soil (A),the transformation of
      iprodione and its toxicity on the (i) abundance of functional microbial groups,
      (ii) activity of key microbial enzymes and (iii) diversity of bacteria, fungi and
      ammonia-oxidizing microorganisms (AOM) using amplicon sequencing. 3,5
      Dichloroaniline (3,5-DCA), the main iprodione TP, was identified as key
      explanatory factor for the persistent reduction in enzymatic activities and
      potential nitrification (PN), and for the observed structural changes in the
      bacterial and fungal community. The abundance of certain bacterial
      (Actinobacteria, Hyphomicrobiaceae, Ilumatobacter and Solirubrobacter) and fungal
      (Pichiaceae) groups were negatively correlated with 3,5-DCA. A subsequent study
      in a fallow agricultural soil (B) showed a limited formation of 3,5-DCA which
      concurred with the lack of effects on nitrification. Direct 3,5-DCA application
      in soil B induced a dose-dependent reduction of PN and NO3--N, which recovered
      with time. In vitro assays with terrestrial AOM verified the greater toxicity of
      3,5-DCA over iprodione. Candidatus Nitrosotalea sinensis Nd2 was the most
      sensitive AOM to both compounds. Our findings build on previous evidence on the
      sensitivity of AOM to pesticides reinforcing their potential utilization as
      indicators of the soil microbial toxicity of pesticides in pesticide
      environmental risk analysis and stressing the need to consider the contribution
      of TPs in the toxicity of pesticides on the soil microbial community.Significance
      statement Pesticide toxicity on soil microorganisms is an emerging issue in
      pesticide risk assessment, dictated by the pivotal role of soil microorganisms on
      ecosystem services. However, the focus has traditionally been on parent
      compounds, while transformation products (TPs) are largely overlooked. We tested
      the hypothesis that TPs can be major contributors on the soil microbial toxicity
      of pesticides, using, iprodione, and its main TP, 3,5-dichloroaniline, as model
      compounds. We demonstrated, by measuring functional and structural endpoints,
      that 3,5-dichloraniline and not iprodione was associated with adverse effects on
      soil microorganisms, with nitrification being mostly affected. Pioneering in
      vitro assays with relevant ammonia-oxidizing bacteria and archaea verified the
      greater toxicity of 3,5-dichloraniline. Our findings are expected to advance
      environmental risk assessment highlighting the potential of ammonia-oxidizing
      microorganisms as indicators of the soil microbial toxicity of pesticides and
      stressing the need to consider the contribution of TPs on pesticides soil
      microbial toxicity.

PMID- 30194101
TI  - Genome Editing Method for the Anaerobic Magnetotactic Bacterium Desulfovibrio
      magneticus RS-1.
AB  - Magnetosomes are complex bacterial organelles that serve as model systems for
      studying bacterial cell biology, biomineralization, and global iron cycling.
      Magnetosome biogenesis is primarily studied in two closely related
      Alphaproteobacteria of the genus Magnetospirillum that form cubooctahedral-shaped
      magnetite crystals within a lipid membrane. However, chemically and structurally
      distinct magnetic particles have been found in physiologically and
      phylogenetically diverse bacteria. Due to a lack of molecular genetic tools, the
      mechanistic diversity of magnetosome formation remains poorly understood.
      Desulfovibrio magneticus RS-1 is an anaerobic sulfate-reducing
      deltaproteobacterium that forms bullet-shaped magnetite crystals. A recent
      forward genetic screen identified 10 genes in the conserved magnetosome gene
      island of D. magneticus that are essential for its magnetic phenotype. However,
      this screen likely missed mutants with defects in crystal size, shape, and
      arrangement. Reverse genetics to target the remaining putative magnetosome genes
      using standard genetic methods of suicide vector integration have not been
      feasible due to the low transconjugation efficiency. Here, we present a reverse
      genetic method for targeted mutagenesis in D. magneticus using a replicative
      plasmid. To test this method, we generated a mutant resistant to 5-fluorouracil
      by making a markerless deletion of the upp gene that encodes uracil
      phosphoribosyltransferase. We also used this method for targeted marker exchange
      mutagenesis by replacing kupM, a gene identified in our previous screen as a
      magnetosome formation factor, with a streptomycin resistance cassette. Overall,
      our results show that targeted mutagenesis using a replicative plasmid is
      effective in D. magneticus and may also be applied to other genetically
      recalcitrant bacteria.IMPORTANCE Magnetotactic bacteria (MTB) are a group of
      organisms that form intracellular nanometer-scale magnetic crystals though a
      complex process involving lipid and protein scaffolds. These magnetic crystals
      and their lipid membranes, termed magnetosomes, are model systems for studying
      bacterial cell biology and biomineralization and are potential platforms for
      biotechnological applications. Due to a lack of genetic tools and unculturable
      representatives, the mechanisms of magnetosome formation in phylogenetically
      deeply branching MTB remain unknown. These MTB contain elongated bullet-/tooth
      shaped magnetite and greigite crystals that likely form in a manner distinct from
      that of the cubooctahedral-shaped magnetite crystals of the genetically tractable
      MTB within the Alphaproteobacteria Here, we present a method for genome editing
      in Desulfovibrio magneticus RS-1, a cultured representative of the deeply
      branching MTB of the class Deltaproteobacteria This marks a crucial step in
      developing D. magneticus as a model for studying diverse mechanisms of magnetic
      particle formation by MTB.

PMID- 30194102
TI  - Oxidative Damage Control during Decay of Wood by Brown Rot Fungus Using Oxygen
      Radicals.
AB  - Brown rot wood-degrading fungi deploy reactive oxygen species (ROS) to loosen
      plant cell walls and enable selective polysaccharide extraction. These ROS,
      including Fenton-generated hydroxyl radicals (HO), react with little specificity
      and risk damaging hyphae and secreted enzymes. Recently, it was shown that brown
      rot fungi reduce this risk, in part, by differentially expressing genes involved
      in HO generation ahead of those coding carbohydrate-active enzymes (CAZYs).
      However, there are notable exceptions to this pattern, and we hypothesized that
      brown rot fungi would require additional extracellular mechanisms to limit ROS
      damage. To assess this, we grew Postia placenta directionally on wood wafers to
      spatially segregate early from later decay stages. Extracellular HO production
      (avoidance) and quenching (suppression) capacities among the stages were
      analyzed, along with the ability of secreted CAZYs to maintain activity
      postoxidation (tolerance). First, we found that H2O2 and Fe2+ concentrations in
      the extracellular environment were conducive to HO production in early (H2O2:Fe2+
      ratio 2:1) but not later (ratio 1:131) stages of decay. Second, we found that
      ABTS radical cation quenching (antioxidant capacity) was higher in later decay
      stages, coincident with higher fungal phenolic concentrations. Third, by
      surveying enzyme activities before/after exposure to Fenton-generated HO, we
      found that CAZYs secreted early, amid HO, were more tolerant of oxidative stress
      than those expressed later and were more tolerant than homologs in the model CAZY
      producer Trichoderma reesei Collectively, this indicates that P. placenta uses
      avoidance, suppression, and tolerance mechanisms, extracellularly, to complement
      intracellular differential expression, enabling this brown rot fungus to use ROS
      to degrade wood.IMPORTANCE Wood is one of the largest pools of carbon on Earth,
      and its decomposition is dominated in most systems by fungi. Wood-degrading fungi
      specialize in extracting sugars bound within lignin, either by removing lignin
      first (white rot) or by using Fenton-generated reactive oxygen species (ROS) to
      "loosen" wood cell walls, enabling selective sugar extraction (brown rot).
      Although white rot lignin-degrading pathways are well characterized, there are
      many uncertainties in brown rot fungal mechanisms. Our study addressed a key
      uncertainty in how brown rot fungi deploy ROS without damaging themselves or the
      enzymes they secrete. In addition to revealing differentially expressed genes to
      promote ROS generation only in early decay, our study revealed three spatial
      control mechanisms to avoid/tolerate ROS: (i) constraining Fenton reactant
      concentrations (H2O2, Fe2+), (ii) quenching ROS via antioxidants, and (iii)
      secreting ROS-tolerant enzymes. These results not only offer insight into natural
      decomposition pathways but also generate targets for biotechnological
      development.

PMID- 30194103
TI  - Genome Analysis, Metabolic Potential, and Predatory Capabilities of Herpetosiphon
      llansteffanense sp. nov.
AB  - Herpetosiphon spp. are ubiquitous, chemoheterotrophic, filamentous gliding
      bacteria with the ability to prey on other microbes through a "wolf pack"
      mechanism. The genus currently comprises four known species (H. aurantiacus, H.
      geysericola, H. giganteus, and H. gulosus), which produce antimicrobial secondary
      metabolites such as siphonazole. As part of a study isolating myxobacterial wolf
      pack predators, we serendipitously isolated a novel environmental strain (CA052B)
      from the edge of a stream at Llansteffan, United Kingdom, which was identified as
      a member of the Herpetosiphon genus. A lawn culture method was utilized to
      analyze the predatory activity of CA052B against 10 prey organisms of clinical
      relevance. CA052B was found to prey on Escherichia coli, Klebsiella pneumoniae,
      Proteus mirabilis, Staphylococcus aureus, Staphylococcus epidermidis,
      Staphylococcus saprophyticus, Enterococcus faecalis, Bacillus subtilis, and
      Candida albicans Purified CA052B outer membrane vesicles also exhibited killing
      activity against the prey organisms when tested by flow cytometry. 16S rRNA
      sequencing of CA052B showed 98 to 99% identity with other Herpetosiphon species
      members. Comparing the genome of CA052B with the publicly available genomes of H.
      aurantiacus and H. geysericola revealed average nucleotide identities of only 84%
      and 91%, respectively, whereas the genome-to-genome distance calculation showed
      sequence identities of 28.2% and 46.6%, respectively. Biochemical
      characterization also revealed distinctions between CA052B and both H. gulosus
      and H. giganteus Thus, strain CA052BT (= DSM 107618T = NBRC 113495T) is proposed
      to be the type strain of a novel species, Herpetosiphon llansteffanense sp. nov.
      The genome sequence of CA052B also revealed diverse secondary metabolite
      biosynthetic clusters, encouraging further exploration of its antibiotic
      production potential.IMPORTANCE Predatory bacteria are able to kill and consume
      other microbes and are therefore of interest as potential sources of new
      antimicrobial substances for applications in the clinic. "Wolf pack" predators
      kill prey by secreting antimicrobial substances into their surroundings, and
      those substances can kill prey organisms independently of the predatory cells.
      The genus Herpetosiphon exhibits wolf pack predation, yet its members are poorly
      described compared to other wolf pack predators, such as the myxobacteria. By
      providing a thorough characterization of a novel Herpetosiphon species, including
      its predatory, biochemical, and genomic features, this study increases our
      understanding of genomic variation within the Herpetosiphon genus and how that
      variation affects predatory activity. This will facilitate future rational
      exploitation of genus members (and other wolf pack predators) as sources of novel
      antimicrobials.

PMID- 30194104
TI  - Steroid Degradation in Comamonas testosteroni TA441: Identification of
      Metabolites and the Genes Involved in the Reactions Necessary before D-Ring
      Cleavage.
AB  - Bacterial steroid degradation has been studied mainly with Rhodococcus equi
      (Nocardia restrictus) and Comamonas testosteroni as representative steroid
      degradation bacteria for more than 50 years. The primary purpose was to obtain
      materials for steroid drugs, but recent studies showed that many genera of
      bacteria (Mycobacterium, Rhodococcus, Pseudomonas, etc.) degrade steroids and
      that steroid-degrading bacteria are globally distributed and found particularly
      in wastewater treatment plants, the soil, plant rhizospheres, and the marine
      environment. The role of bacterial steroid degradation in the environment is,
      however, yet to be revealed. To uncover the whole steroid degradation process in
      a representative steroid-degrading bacterium, C. testosteroni, to provide basic
      information for further studies on the role of bacterial steroid degradation, we
      elucidated the two indispensable oxidative reactions and hydration before D-ring
      cleavage in C. testosteroni TA441. In bacterial oxidative steroid degradation, A-
      and B-rings of steroids are cleaved to produce 2-hydroxyhexa-2,4-dienoic acid and
      9,17-dioxo-1,2,3,4,10,19-hexanorandrostan-5-oic acid. The latter compound was
      revealed to be degraded to the coenzyme A (CoA) ester of 9alpha-hydroxy-17-oxo
      1,2,3,4,5,6,10,19-octanorandrostan-7-oic acid, which is converted to the CoA
      ester of 9,17-dioxo-1,2,3,4,5,6,10,19-octanorandrostan-7-oic acid by ORF31
      encoded hydroxylacyl dehydrogenase (ScdG), followed by conversion to the CoA
      ester of 9,17-dioxo-1,2,3,4,5,6,10,19-octanorandrost-8(14)-en-7-oic acid by ORF4
      encoded acyl-CoA dehydrogenase (ScdK). Then, a water molecule is added by the
      ORF5-encoded enoyl-CoA hydratase (ScdY), which leads to the cleavage of the D
      ring. The conversion by ScdG is presumed to be a reversible reaction. The
      elucidated pathway in C. testosteroni TA441 is different from the corresponding
      pathways in Mycobacterium tuberculosis H37Rv.IMPORTANCE Studies on representative
      steroid degradation bacteria Rhodococcus equi (Nocardia restrictus) and Comamonas
      testosteroni were initiated more than 50 years ago primarily to obtain materials
      for steroid drugs. A recent study showed that steroid-degrading bacteria are
      globally distributed and found particularly in wastewater treatment plants, the
      soil, plant rhizospheres, and the marine environment, but the role of bacterial
      steroid degradation in the environment is yet to be revealed. This study aimed to
      uncover the whole steroid degradation process in C. testosteroni TA441, in which
      major enzymes for steroidal A- and B-ring cleavage were elucidated, to provide
      basic information for further studies on bacterial steroid degradation. C.
      testosteroni is suitable for exploring the degradation pathway because the
      involvement of degradation-related genes can be determined by gene disruption. We
      elucidated the two indispensable oxidative reactions and hydration before D-ring
      cleavage, which appeared to differ from those present in Mycobacterium
      tuberculosis H37Rv.

PMID- 30194105
TI  - Priming of Plant Growth Promotion by Volatiles of Root-Associated Microbacterium
      spp.
AB  - Volatile compounds produced by plant-associated microorganisms represent a
      diverse resource to promote plant growth and health. Here, we investigated the
      effect of volatiles from root-associated Microbacterium species on plant growth
      and development. Volatiles of eight strains induced significant increases in
      shoot and root biomass of Arabidopsis but differed in their effects on root
      architecture. Microbacterium strain EC8 also enhanced root and shoot biomass of
      lettuce and tomato. Biomass increases were also observed for plants exposed only
      briefly to volatiles from EC8 prior to transplantation of the seedlings to soil.
      These results indicate that volatiles from EC8 can prime plants for growth
      promotion without direct and prolonged contact. We further showed that the
      induction of plant growth promotion is tissue specific; that is, exposure of
      roots to volatiles from EC8 led to an increase in plant biomass, whereas shoot
      exposure resulted in no or less growth promotion. Gas chromatography-quadrupole
      time of flight mass spectometry (GC-QTOF-MS) analysis revealed that EC8 produces
      a wide array of sulfur-containing compounds, as well as ketones. Bioassays with
      synthetic sulfur volatile compounds revealed that the plant growth response to
      dimethyl trisulfide was concentration-dependent, with a significant increase in
      shoot weight at 1 MUM and negative effects on plant biomass at concentrations
      higher than 1 mM. Genome-wide transcriptome analysis of volatile-exposed
      Arabidopsis seedlings showed upregulation of genes involved in assimilation and
      transport of sulfate and nitrate. Collectively, these results show that root
      associated Microbacterium primes plants, via the roots, for growth promotion,
      most likely via modulation of sulfur and nitrogen metabolism.IMPORTANCE In the
      past decade, various studies have described the effects of microbial volatiles on
      other (micro)organisms in vitro, but their broad-spectrum activity in vivo and
      the mechanisms underlying volatile-mediated plant growth promotion have not been
      addressed in detail. Here, we revealed that volatiles from root-associated
      bacteria of the genus Microbacterium can enhance the growth of different plant
      species and can prime plants for growth promotion without direct and prolonged
      contact between the bacterium and the plant. Collectively, these results provide
      new opportunities for sustainable agriculture and horticulture by exposing roots
      of plants only briefly to a specific blend of microbial volatile compounds prior
      to transplantation of the seedlings to the greenhouse or field. This strategy has
      no need for large-scale introduction or root colonization and survival of the
      microbial inoculant.

PMID- 30194106
TI  - Molecular Characterization of Binding Loop E in the Nematode Cys-Loop GABA
      Receptor.
AB  - Nematodes exhibit a vast array of cys-loop ligand-gated ion channels with unique
      pharmacologic characteristics. However, many of the structural components that
      govern the binding of various ligands are unknown. The nematode cys-loop GABA
      receptor uncoordinated 49 (UNC-49) is an important receptor found at
      neuromuscular junctions that plays an important role in the sinusoidal movement
      of worms. The unique pharmacologic features of this receptor suggest that there
      are structural differences in the agonist binding site when compared with
      mammalian receptors. In this study, we examined each amino acid in one of the
      main agonist binding loops (loop E) via the substituted cysteine accessibility
      method (SCAM) and analyzed the interaction of various residues by molecular
      dynamic simulations. We found that of the 18 loop E mutants analyzed, H142C,
      R147C, and S157C had significant changes in GABA EC50 and were accessible to
      modification by a methanethiosulfonate reagent (MTSET) resulting in a change in I
      GABA In addition, the residue H142, which is unique to nematode UNC-49 GABA
      receptors, appears to play a negative role in GABA sensitivity as its mutation to
      cysteine increased sensitivity to GABA and caused the UNC-49 receptor partial
      agonist 5-aminovaleric acid (DAVA) to behave as a full agonist. Overall, this
      study has revealed potential differences in the agonist binding pocket between
      nematode UNC-49 and mammalian GABA receptors that could be exploited in the
      design of novel anthelmintics.

PMID- 30194107
TI  - Effects of HCN Channels in the Rostral Ventrolateral Medulla Contribute to the
      Cardiovascular Effects of Propofol.
AB  - Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels were reported
      to express in the well-known vasomotor region, rostral ventrolateral medulla
      (RVLM), and can be inhibited by propofol. However, whether HCN channels in RVLM
      contribute to propofol-induced cardiovascular depression remains unclear. We
      recorded the hemodynamic changes when either continuous intravenous infusions or
      microinjections of propofol and ZD-7288 (4-ethylphenylamino-1,2-dimethyl-6
      methylaminopyrimidinium chloride; HCN channel blocker) in RVLM. Expressions of
      HCN channels in RVLM neurons of mice of different ages were examined by
      quantitative real-time polymerase chain reaction and Western blotting. The
      effects of propofol and ZD-7288 on HCN channels and the excitability of RVLM
      neurons were examined by electrophysiological recording. Propofol (1.25, 2.5, 5,
      and 7.5 mg/kg per minute, i.v., 10 minutes) decreased mean arterial pressure
      (MAP) and heart rate (HR) in a concentration-dependent manner in wild-type mice
      that were markedly attenuated in HCN1 knockout mice. Bilateral microinjection of
      propofol (1%, 0.1 MUl) in RVLM caused a sharp and pronounced drop in MAP and HR
      values, which were abated by pretreatment with ZD-7288. In electrophysiological
      recording, propofol (5, 10, and 20 MUM) concentration-dependently inhibited HCN
      current, increased input resistance, decreased firing rate, and caused membrane
      hyperpolarization in RVLM neurons. These actions of propofol were attenuated by
      ZD-7288 pretreatment. The mRNA and protein level of HCN channels increased in an
      age-dependent manner, which may contribute to the age-dependent increase in the
      sensitivity to propofol. Our results indicated that the inhibition of HCN
      channels in RVLM neurons may contribute to propofol-induced cardiovascular
      inhibition.

PMID- 30194108
TI  - Transient in-stent stenosis at mid-term angiographic follow-up in patients
      treated with SILK flow diverter stents: incidence, clinical significance and long
      term follow-up.
AB  - BACKGROUND: Little is known about in-stent stenosis (ISS) in patients with
      aneurysms treated with flow diverter (FD) stents. The reported incidence in the
      literature varies significantly. OBJECTIVE: The aim of this study was to assess
      the incidence, severity, distribution, clinical significance, and possible
      predictors for ISS. METHODS: Between July 2012 and June 2016 we retrospectively
      reviewed all patients treated with SILK FDs in our center. Only cases with short
      term (4+/-2 months) and long-term (>1 year) follow-ups with digital subtraction
      angiograms were included. ISS was graded as mild (<25%), moderate (25-50%) or
      severe (>50%). The following predictors for ISS were assessed: gender, age, the
      presence of subarachnoid hemorrhage, aneurysm size, location, occlusion status,
      and post-stenting angioplasty. RESULTS: Thirty-six patients met the inclusion
      criteria. At mid-term follow-up, ISS was observed in 16/36 patients (44%). Eleven
      patients (69%) had mild ISS, three (19%) moderate, and two (12%) severe ISS. ISS
      was diffuse in 11 patients (69%) and focal in five patients (31%). All patients
      were asymptomatic. Thirteen patients were maintained on dual antiplatelet therapy
      and three on aspirin alone. At long-term follow-up, complete ISS resolution was
      seen in 11 patients, improvement in three and worsening in two patients. No de
      novo ISS occurrence was observed. On univariate analysis there was no significant
      predictor for ISS. CONCLUSIONS: Transient ISS after FD deployment is a common
      asymptomatic finding on mid-term angiographic follow-up. Complete resolution or
      improvement at long-term follow-up is seen in most patients who are maintained on
      dual antiplatelet therapy.

PMID- 30194109
TI  - eTICI reperfusion: defining success in endovascular stroke therapy.
AB  - BACKGROUND: Revascularization after endovascular therapy for acute ischemic
      stroke is measured by the Thrombolysis In Cerebral Infarction (TICI) scale, yet
      variability exists in scale definitions. We examined the degree of reperfusion
      with the expanded TICI (eTICI) scale and association with outcomes in the HERMES
      collaboration of recent endovascular trials. METHODS: The HERMES Imaging Core,
      blind to all other data, evaluated angiography after endovascular therapy in
      HERMES. A battery of TICI scores (mTICI, TICI, TICI2C) was used to define
      reperfusion of the initial target occlusion defined by non-invasive imaging and
      conventional angiography. RESULTS: Angiography of 801 subjects was available,
      including 797 defined by non-invasive imaging (154 internal carotid artery (ICA),
      583 M1, 60 M2) and 748 by conventional angiography (195 ICA, 459 M1, 94 M2).
      Among 729 subjects in whom the reperfusion grade could be established, using
      eTICI (3=100%, 2C=90-99%, 2b67=67-89%, 2b50=50-66%) of the conventional
      angiography target occlusion, there were 63 eTICI 3 (9%), 166 eTICI 2c (23%), 218
      eTICI 2b67 (30%), 103 eTICI 2b50 (14%), 100 eTICI 2a (14%), 19 eTICI 1 (3%), and
      60 eTICI 0 (8%). Modified Rankin Scale shift analyses from baseline to 90 days
      showed that increasing TICI grades were linked with better outcomes, with
      significant distinctions between TICI 0/1 versus 2a (p=0.028), 2a versus 2b50
      (p=0.017), and 2b50 versus 2b67 (p=0.014). CONCLUSIONS: The benefit of
      endovascular therapy in HERMES was strongly associated with increasing degrees of
      reperfusion defined by eTICI. The eTICI metric identified meaningful distinctions
      in clinical outcomes and may be used in future studies and routine practice.

PMID- 30194110
TI  - Crossing Y-Solitaire thrombectomy as a rescue treatment for refractory acute
      occlusions of the middle cerebral artery.
AB  - BACKGROUND: Mechanical thrombectomy using a stent retriever has become the
      standard of care for acute large-vessel occlusions in the anterior circulation.
      Clots that are refractory to single stent retriever thrombectomy remain a
      challenge for neurointerventionalists. OBJECTIVE: To assess the efficacy and
      safety of double stent retriever (crossing Y-Solitaire) thrombectomy as a rescue
      treatment for acute middle cerebral artery (MCA) occlusions that are refractory
      to single stent retriever thrombectomy. METHODS: We retrospectively reviewed the
      databases of our hospitals to identify patients who presented with an acute MCA
      occlusion and were treated with crossing Y-Solitaire thrombectomy. The
      angiographic (Thrombolysis in Cerebral Infarction (TICI) scale) and clinical
      outcomes (National Institutes of Health Stroke Scale (NIHSS) and modified Rankin
      Scale (mRS) scores) and complications were assessed. RESULTS: Ten patients were
      included in the study. The median initial NIHSS score and Alberta Stroke Program
      Early CT Score (ASPECTS) were 19.0 and 9.6, respectively. Crossing Y-Solitaire
      thrombectomy was performed as a rescue technique after unsuccessful single
      Solitaire thrombectomy passes in all cases. Successful recanalization (TICI 2b/3)
      was achieved in 8 (80%) patients. We observed asymptomatic reperfusion
      hemorrhages in 2 (20%) patients. No procedural related complications were seen
      other than reversible vasospasms in 5 (50%) patients. Sixty percent of the
      patients had a mRS score of between 2 and 0 at 90 days after the procedure. There
      was no mortality. CONCLUSION: Crossing Y-Solitaire thrombectomy seems to be an
      effective and safe alternative rescue technique to treat refractory MCA
      bifurcation occlusions that are refractory to standard thrombectomy procedures.

PMID- 30194111
TI  - Remarkably Robust Antiviral Immune Response despite Combined Deficiency in
      Caspase-8 and RIPK3.
AB  - Caspase-8 (Casp8)-mediated signaling triggers extrinsic apoptosis while
      suppressing receptor-interacting protein kinase (RIPK) 3-dependent necroptosis.
      Although Casp8 is dispensable for the development of innate and adaptive immune
      compartments in mice, the importance of this proapoptotic protease in the
      orchestration of immune response to pathogens remains to be fully explored. In
      this study, Casp8-/-Ripk3-/- C57BL/6 mice show robust innate and adaptive immune
      responses to the natural mouse pathogen, murine CMV. When young, these mice lack
      lpr-like lymphoid hyperplasia and accumulation of either B220 + CD3+ or B220
      CD3+CD4+ and CD8+ T cells with increased numbers of immature myeloid cells that
      are evident in older mice. Dendritic cell activation and cytokine production
      drive both NK and T cell responses to control viral infection in these mice,
      suggesting that Casp8 is dispensable to the generation of antiviral host defense.
      Curiously, NK and T cell expansion is amplified, with greater numbers observed by
      7 d postinfection compared with either Casp8+/-Ripk3-/- or wild type
      (Casp8+/+Ripk3+/+ ) littermate controls. Casp8 and RIPK3 are natural targets of
      virus-encoded cell death suppressors that prevent infected cell apoptosis and
      necroptosis, respectively. It is clear from the current studies that the
      initiation of innate immunity and the execution of cytotoxic lymphocyte functions
      are all preserved despite the absence of Casp8 in responding cells. Thus, Casp8
      and RIPK3 signaling is completely dispensable to the generation of immunity
      against this natural herpesvirus infection, although the pathways driven by these
      initiators serve as a crucial first line for host defense within virus-infected
      cells.

PMID- 30194113
TI  - 'It's now time for OVs to name their price'.

PMID- 30194112
TI  - Haptoglobin Is a Divergent MASP Family Member That Neofunctionalized To Recycle
      Hemoglobin via CD163 in Mammals.
AB  - In mammals, haptoglobin (Hp) is an acute-phase plasma protein that binds with
      high affinity to hemoglobin (Hb) released by intravascular hemolysis. The
      resultant Hp-Hb complexes are bound and cleared by the scavenger receptor CD163,
      limiting Hb-induced oxidative damage. In this study, we show that Hp is a
      divergent member of the complement-initiating MASP family of proteins, which
      emerged in the ancestor of jawed vertebrates. We demonstrate that Hp has been
      independently lost from multiple vertebrate lineages, that characterized Hb
      interacting residues of mammals are poorly conserved in nonmammalian species
      maintaining Hp, and that the extended loop 3 region of Hp, which mediates CD163
      binding, is present only in mammals. We show that the Hb-binding ability of
      cartilaginous fish (nurse shark, Ginglymostoma cirratum; small-spotted catshark,
      Scyliorhinus canicula; and thornback ray, Raja clavata) and teleost fish (rainbow
      trout, Oncorhynchus mykiss) Hp is species specific, and where binding does occur
      it is likely mediated through a different structural mechanism to mammalian Hp.
      The continued, high-level expression of Hp in cartilaginous fishes in which Hb
      binding is not evident signals that Hp has (an)other, yet unstudied, role(s) in
      these species. Previous work indicates that mammalian Hp also has secondary,
      immunomodulatory functions that are independent of Hb binding; our work suggests
      these may be remnants of evolutionary more ancient functions, retained after Hb
      removal became the primary role of Hp in mammals.

PMID- 30194114
TI  - 'Urgent' need to review revalidation process for OVs.

PMID- 30194116
TI  - Problems with pet ID are still 'not solved'.

PMID- 30194117
TI  - Warning follows reports of growing cascade violations.

PMID- 30194120
TI  - Looking for alternative animal feeds.
AB  - Josh Loeb explains how one startup company in Poland is exploring the use of
      invertebrates for animal feed.

PMID- 30194124
TI  - Equine disease surveillance: quarterly summary.

PMID- 30194125
TI  - Whose role is preventive healthcare in the veterinary practice?

PMID- 30194127
TI  - Severe summer scour syndrome in recently turned out dairy calves.

PMID- 30194128
TI  - African swine fever in China.

PMID- 30194129
TI  - Testing for TB in camelids.

PMID- 30194131
TI  - Influencing animal welfare after Brexit.

PMID- 30194132
TI  - Veterinary care for a farm dog.
AB  - Farmer Joe Stanley debates access to veterinary care for his dog.

PMID- 30194137
TI  - Enhancing immunotherapy of STING agonist for lymphoma in preclinical models.
AB  - Direct activation of tumor infiltrating antigen-presenting cells (APCs) by
      intratumoral injection of STING agonists (STINGa) leads to regression of the
      treated lymphoma tumor. Because STING activation induces apoptosis in lymphoma
      cells in vitro, we distinguished between the direct therapeutic vs the indirect
      immunotherapeutic properties of STINGa in vivo. Employing wild-type or STING
      knockout hosts bearing either wild-type or STING knockout tumor cells, we
      demonstrated that local tumor regression is totally dependent on STING expression
      by the host and is therefore immune mediated. However, distant untreated tumors
      are weakly affected after injection of STINGa to a single tumor site. Therefore,
      using the STINGa currently being tested in clinical trials, we screened for
      immunomodulatory agents that could synergize with the STING pathway to induce a
      systemic antitumor immune response and regression of distant tumors. We combined
      the STINGa with agents that improve APC or T-cell function. We found that
      modulation of both APCs and T cells can enhance control of distant lymphoma
      tumors by STINGa. In particular, adding an anti-GITR antibody induced lymphocyte
      expansion in the lymph node draining the treated site followed by increased T
      cell infiltration in the distant tumor. Furthermore, more of these CD8 T cells at
      the distant site expressed PD-1. Therefore, blockade of PD-1 further enhanced
      tumor control at the distant site, leading to cure in 50% of the mice. These
      preclinical data provide the rationale for testing local injection of STINGa
      followed by agonistic anti-GITR and anti-PD-1 antibodies as immunotherapy for
      human lymphoma.

PMID- 30194138
TI  - Microenvironmental immune cell signatures dictate clinical outcomes for PTCL-NOS.
AB  - Peripheral T-cell lymphoma (PTCL), not otherwise specified (PTCL-NOS) is among
      the most common disease subtypes of PTCL, one that exhibits heterogeneous
      clinicopathological features. Although multiple disease-stratification models,
      including the cell-of-origin or gene-expression profiling methods, have been
      proposed for this condition, their clinical significance remains unclear. To
      establish a clinically meaningful stratification model, we analyzed gene
      expression signatures of tumors and tumor-infiltrating immune cells using the
      nCounter system, which enables accurate quantification of low abundance and/or
      highly fragmented transcripts. To do so, we assessed transcripts of 120 genes
      related to cancer or immune cells using tumor samples from 68 newly diagnosed
      PTCL-NOS patients and validated findings by immunofluorescence in tumor sections.
      We show that gene-expression signatures representing tumor-infiltrating immune
      cells, but not those of cancerous T cells, dictate patient clinical outcomes.
      Cases exhibiting both B-cell and dendritic cell (DC) signatures (BD subgroup)
      showed favorable clinical outcomes, whereas those exhibiting neither B-cell nor
      DC signatures (non-BD subgroup) showed extremely poor prognosis. Notably, half of
      the non-BD cases exhibited a macrophage signature, and macrophage infiltration
      was evident in those cases, as revealed by immunofluorescence. Importantly, tumor
      infiltrating macrophages expressed the immune-checkpoint molecules programmed
      death ligand 1/2 and indoleamine 2, 3-dioxygenase 1 at high levels, suggesting
      that checkpoint inhibitors could serve as therapeutic options for patients in
      this subgroup. Our study identifies clinically distinct subgroups of PTCL-NOS and
      suggests a novel therapeutic strategy for 1 subgroup associated with a poor
      prognosis. Our data also suggest functional interactions between cancerous T
      cells and tumor-infiltrating immune cells potentially relevant to PTCL-NOS
      pathogenesis.

PMID- 30194139
TI  - Living inside the box: environmental effects on mouse models of human disease.
AB  - The impact of the laboratory environment on animal models of human disease,
      particularly the mouse, has recently come under intense scrutiny regarding both
      the reproducibility of such environments and their ability to accurately
      recapitulate elements of human environmental conditions. One common objection to
      the use of mice in highly controlled facilities is that humans live in much more
      diverse and stressful environments, which affects the expression and
      characteristics of disease phenotypes. In this Special Article, we review some of
      the known effects of the laboratory environment on mouse phenotypes and compare
      them with environmental effects on humans that modify phenotypes or, in some
      cases, have driven genetic adaptation. We conclude that the 'boxes' inhabited by
      mice and humans have much in common, but that, when attempting to tease out the
      effects of environment on phenotype, a controlled and, importantly, well
      characterized environment is essential.

PMID- 30194140
TI  - Directed Therapies in Anaplastic Lymphoma Kinase-rearranged Non-small Cell Lung
      Cancer.
AB  - Anaplastic lymphoma kinase (ALK) rearrangements were first implicated as driving
      mutations in non-small cell lung cancer in 2007. Since then, a number of novel,
      small-molecule inhibitors directed against the ALK receptor have demonstrated
      superiority over standard chemotherapies in the treatment of ALK rearrangement
      positive lung cancer. Of considerable importance when considering such therapies
      is the ability of each to overcome mutations conferring acquired resistance, as
      well as penetrate the central nervous system (CNS), the most common site of
      metastasis and traditionally the most difficult to breach. Herein is a review of
      the efficacy, indications, and degree of CNS penetration for the ALK-targeting
      agents crizotinib, ceretinib, alectinib, brigatinib, and lorlatinib, as well as a
      summary of ongoing clinical trials comparing these drugs.

PMID- 30194141
TI  - Whole Lung Irradiation in Patients with Osteosarcoma and Ewing Sarcoma.
AB  - BACKGROUND/AIM: Whole lung irradiation (WLI) represents standard therapy for
      patients with pulmonary metastases from Ewing sarcoma although the impact on
      clinical outcomes and toxicity is still unclear. The aim of this study was to
      evaluate toxicity after WLI in patients with Ewing sarcoma and osteosarcoma as
      well as overall survival (OS) and event-free survival (EFS). MATERIALS AND
      METHODS: A systematic review of studies on bilateral pulmonary irradiation
      treatments for prophylactic or curative therapy was performed based on PRISMA
      methodology. Data base searches on PubMed and Cochrane Library from the earliest
      time possible through 31st March 2018 were carried out. Combination with other
      treatments, such as chemotherapy and surgery were allowed. Only articles
      published in English were considered. RESULTS: Toxicity was evaluated in 13 of
      the 14 analyzed studies (640 patients). Reported lung acute toxicity grade >=3
      ranged between 0.0 and 12.2%. Three studies reported 12 cases (1.8%) of severe
      pneumonitis. Grade >=2 late toxicity was mainly recorded in patients who received
      boost irradiation, previous thoracic surgery, chemotherapy or who were smokers.
      Lack of a significant impact of WLI on OS was reported in comparative studies
      although patients treated with WLI showed higher survival in most individual
      studies. CONCLUSION: Although the rate of severe toxicity was very low, the real
      impact of WLI on patients' outcomes remains unproven, probably due to the narrow
      dose limits that can be delivered to the whole lung parenchyma. New strategies to
      prevent or treat lung metastases in these patients should be tested. Ultra
      fractionated radiotherapy concurrent with modern chemotherapy protocols could be
      tested in this setting due to the chemo-sensitizing effect and negligible radio
      induced toxicity of fraction doses <0.5 Gy.

PMID- 30194142
TI  - Metastatic Spinal Cord Compression: Unraveling the Diagnostic and Therapeutic
      Challenges.
AB  - Malignant spinal cord compression (MSCC) is one of the most devastating
      complications of cancer. Patients often present with a history of progressive
      pain, paralysis, sensory loss, progressive spinal deformity, and loss of
      sphincter control. It is an emergency that requires rapid decision making on the
      part of several specialists, given the risk of permanent spinal cord injury or
      death. The goals of treatment in spinal metastases are pain control and
      improvement of neurological function in order to achieve better quality of life
      (QoL). The standard of care in most cases is rapid initiation of corticosteroids
      in combination with either surgical decompression in case of an operable
      candidate, followed by radiation therapy (RT) or RT alone. Surgery is associated
      with improved outcomes, but is not appropriate for many patients presenting with
      advanced symptoms of MSCC, such as paralysis, or those with a poor performance
      status, or cachexic state, as well as altered mental conditions, co-morbidities,
      surgical risks, and limited life expectancy. On the other hand, aggressive
      surgical treatment and post-operative RT is advocated for those with more
      favorable prognosis, or who are expected to have higher neurological recovery
      potential. Many candidates may require for combined anterior and posterior
      approaches to effectively deal with the compressive pathology and stabilize the
      spine. Most patients are presently treated by primary RT, given with the aim of
      improving function and symptom management. However, there is still debate
      regarding the most appropriate RT schedule. Rehabilitation can serve to relieve
      symptoms, QoL, enhance functional independence, and prevent further
      complications. Ambulatory status has been found to be an important prognostic
      factor for patients with MSCC.

PMID- 30194143
TI  - Radiation-induced Demyelination and Remyelination in the Central Nervous System:
      A Literature Review.
AB  - Therapeutic radiation applied to the central nervous system concomitant with or
      followed by surgery and chemotherapy induces significant pathologic demyelination
      depending upon tumor volume, dosage, field of treatment, and age of patient, with
      consequent exacerbation of significant impairment of mental function including
      personality change, memory deficiencies, confusion, learning difficulties and
      dementia. These adverse clinical events may be ameliorated by the application of
      remyelinating measures including nutrition, supplements and pharmaceuticals
      prophylactically, concomitant with radiation or post-radiation treatment.

PMID- 30194144
TI  - Effects of Biguanides on Growth and Glycolysis of Bladder and Colon Cancer Cells.
AB  - : Background/ Aim: There is evidence that inhibitory effects of biguanides on
      oxidative phosphorylation require uptake of biguanides into the mitochondria. In
      this study the action of two biguanides that enter the mitochondria (buformin and
      phenformin) were compared with the action of two biguanides with poor uptake
      (phenyl biguanide and proguanil). MATERIALS AND METHODS: Effects on growth,
      glucose uptake and medium acidification were studied with two human colon cancer
      cells and seven bladder cancer cell lines. RESULTS: Growth inhibition was
      greatest with proguanil followed by phenformin, buformin and phenylbiguanide. In
      contrast, increased glucose uptake and acidification of the medium was observed
      with buformin and phenformin, with no change or less acidification of the medium
      with phenyl biguanide and proguanil. CONCLUSION: The effect of biguanides on
      glucose metabolism requires mitochondrial uptake while the mechanism for growth
      inhibition by biguanides remains to be defined.

PMID- 30194145
TI  - Pax-5 Inhibits Breast Cancer Proliferation Through MiR-215 Up-regulation.
AB  - BACKGROUND/AIM: In breast cancer, Pax-5 promotes pro-epithelial features and
      suppresses malignant cancer processes. However, the molecular mechanism of this
      antitumor activity remains largely unknown. This study aimed to identify the
      cellular roles of Pax-5-regulated miRNAs in breast cancer progression. MATERIALS
      AND METHODS: After transient transfection of Pax-5 in MDA-MB-231 breast cancer
      cells, Pax-5-regulated miRNA expression was examined by next-generation
      sequencing. The identified Pax-5-regulated miRNAs were then validated by qRT-PCR
      and examined for the roles they play in breast cancer cells. RESULTS: Pax-5 was
      shown to be an effective modulator of miR-215-5p and its target genes. MiR-215
      inhibited cell proliferation and migration of breast cancer cells, but not cell
      invasion. More importantly, Pax-5-induced suppression of cancer cell
      proliferation and migration was found to be miR-215-dependent. Interestingly, miR
      215 profiling in clinical tumor samples showed that miR-215 expression was lower
      in cancer tissues in comparison to healthy controls. CONCLUSION: Pax-5 reduces
      breast cancer proliferation and migration through up-regulation of the tumor
      suppressor miR-215. This result supports the use of miR-215 as a prognostic
      marker for breast cancer.

PMID- 30194146
TI  - Identification of a Novel MicroRNA Panel Associated with Metastasis Following
      Radical Prostatectomy for Prostate Cancer.
AB  - BACKGROUND/AIM: This is a case control study designed to identify one or more
      novel microRNA sequences associated with metastasis following radical
      prostatectomy for clinically localized prostate cancer. MATERIALS AND METHODS:
      Samples were obtained from patients with clinical evidence of metastatic disease
      following surgery (cases) and patients who showed no evidence of metastasis or
      biochemical recurrence at least 5 years following surgery (controls) as
      identified from a single-center, institutional database. Cases and controls were
      matched for tumor grade and duration of follow-up. RESULTS: Whole miRNome
      analysis identified 2,792 expressed miRNAs in 19 patient pairs. The 497 miRNA
      sequences with reads per million over 10, were used for analysis, bootstrapping
      with backward selection identified a panel of 5-miRNA (miR-17-3p, miR-27a-3p, miR
      200a-3p, miR-375, and miR-376b-3p) with a risk score strongly associated with
      metastasis (AUC=89.5%, 95%CI=79.5-99.5%). Methodologically, most studies use the
      magnitude of differential expression with or without clinical judgement for
      selection of predictors for inclusion in panels. In order to strengthen the
      predictive model, a selection strategy was employed, bootstrapping with automated
      backwards selection, which relied on the strength of association for inclusion.
      CONCLUSION: A genome-wide analysis of microRNA expression identified a panel of 5
      miRNAs strongly associated with prostate cancer metastasis following radical
      prostatectomy.

PMID- 30194147
TI  - Establishment and Characterization of a Novel Human Clear-cell Sarcoma of Soft
      tissue Cell Line, RSAR001, Derived from Pleural Effusion of a Patient with
      Pleural Dissemination.
AB  - BACKGROUND/AIM: Clear cell sarcoma (CCS) of soft tissue is exceedingly rare and
      frequently exhibits aggressive behavior. Toward the goals of improving the
      aggressive course and poor prognosis of CCS, and establish new therapeutic
      methods, molecular genetic and biological characterizations of CCS are required.
      MATERIALS AND METHODS: A new human CCS cell line (designated RSAR001) was
      established from the pleural effusion of a 44-year-old man with multiple lung
      metastases and pleural dissemination. The cell line and its xenograft were
      characterized including their morphology, immunohistochemistry, cytogenetic
      analysis, reverse transcription-polymerase chain reaction, direct sequencing
      analysis, and fluorescence in situ hybridization analysis. RESULTS: The cell line
      has been maintained for over 12 months with more than 50 passages. RSAR001 cells
      exhibited a fascicular or diffuse growth pattern of short spindle- or oval-shaped
      cells with clear cytoplasm in heterotransplanted tumor, that was similar to the
      primary tumor. Immunophenotypically, RSAR001 cells in vitro and in vivo exhibited
      almost the same characteristics as the primary tumor. Cytogenetic analyses
      revealed a translocation, t(12;22)(q13;q12). Reverse transcription-polymerase
      chain reaction and direct sequencing analysis detected transcripts of the Ewing
      sarcoma breakpoint region 1-activating transcription factor 1 (EWSR1-ATF1) type 1
      fusion gene. Fluorescence in situ hybridization using a break-apart probe for the
      EWSR1 gene on 22q12 showed a rearrangement. CONCLUSION: These findings indicate
      that the RSAR001 cell line harbors EWSR1-ATF1 type 1 chimeric fusion gene, which
      is specific to CCS. RSAR001 cells might be useful for investigating biological
      behaviors and developing new treatments such as molecular-targeting antitumor
      drugs or immunological drugs for CCS.

PMID- 30194148
TI  - Effect of Vitamin D on Paclitaxel Efficacy in Triple-negative Breast Cancer Cell
      Lines.
AB  - BACKGROUND/AIM: Triple-negative breast cancer (TNBC) is a highly aggressive
      breast cancer that disproportionately affects women with darker skin and is often
      treated with paclitaxel (PTX). Here, the effect of vitamin D on p53-positive
      DU4475 cells and its ability to decrease the IC50 of PTX in these cells were
      investigated. MATERIALS AND METHODS: The growth inhibitory effects of vitamin D
      on DU4475 cells and the effect of PTX plus vitamin D on overall TNBC cell
      viability was assessed using CellTiter-Glo(r). RESULTS: Vitamin D increased
      proliferation of DU4475 cells at low concentrations and lowered the IC50 of PTX.
      However, it did not change the IC50 of PTX in MDA-MB-231 cells which remained
      largely viable. CONCLUSION: The effect of vitamin D on DU4475 cell viability was
      different than in other TNBC cells. The effect of PTX on DU4475 cells was
      enhanced with vitamin D. MDA-MB-231 cells were relatively resistant to the
      effects of PTX.

PMID- 30194149
TI  - Novel Human NK Cell Line Carrying CAR Targeting EGFRvIII Induces Antitumor
      Effects in Glioblastoma Cells.
AB  - BACKGROUND/AIM: Natural killer (NK) cells are considered potential antitumor
      effector cells. The aim of this study was to establish a novel type of a chimeric
      antigen receptor (CAR) NK cell line (CAR-KHYG-1) specific for epidermal growth
      factor receptor variant III (EGFRvIII)-expressing tumors and investigate the anti
      tumor activity of EGFRvIII-specific-CAR-KHYG-1 (EvCAR-KHYG-1). MATERIALS AND
      METHODS: EvCAR-KHYG-1 was established by self-inactivated lentiviral-based
      transduction of the EvCAR gene and magnetic bead-based purification of EvCAR
      expressing NK cells. The anti-tumor effects of EvCAR-KHYG-1 were evaluated using
      growth inhibition and apoptosis detection assays in glioblastoma (GBM) cell lines
      (EGFRvIII-expressing and non-expressing U87MG). RESULTS: The findings
      demonstrated that EvCAR-KHYG-1 inhibited GBM cell-growth via apoptosis in an
      EGFRvIII-expressing specific manner. CONCLUSION: This is the first study to
      establish a CAR NK cell line based on the human NK cell line KHYG-1. Therapy with
      EvCAR-KHYG-1 may be an effective treatment option for GBM patients.

PMID- 30194150
TI  - Implication of BIS in the Migration and Invasion of A549 Non-small Cell Lung
      Cancer Cells.
AB  - BACKGROUND/AIM: High expression of the Bcl-2-interacting cell death suppressor
      (BIS), an anti-apoptotic protein, in various human cancers is linked to a poor
      outcome. The purpose of this study was to clarify whether BIS is associated with
      the migration and invasive characteristics of A549 cells. MATERIALS AND METHODS:
      BIS-knockout (KO) cells were prepared by the CRISPR/Cas9 method. The aggressive
      behaviors of A549 cells were analyzed by wound healing and a transwell invasion
      assay as well as 3D spheroid culture. RESULTS: BIS depletion resulted in
      significant inhibition of the migration and invasive potential of A549 cells
      which was accompanied by an increased ratio of E-cadherin/N-cadherin and a
      decrease in the mRNA levels of Zeb1, Snail, Slug and MMP-2. NF-KB activity was
      suppressed in BIS-KO A549 cells due to the decrease in p65 protein levels, but
      not in mRNA levels. CONCLUSION: BIS regulates cell invasion and the induction of
      the epithelial-mesenchymal transition (EMT) phenotype in A549 cells probably via
      the NF-KB signaling pathway.

PMID- 30194151
TI  - The Auricular VX2 Carcinoma Is a Suitable Animal Model for Identifying Biomarkers
      for HNSCC Therapy Response.
AB  - BACKGROUND/AIM: The rabbit auricular VX2 carcinoma is an established animal model
      for human head and neck squamous cell carcinoma (HNSCC). Previously, we observed
      that intraperitoneal oxidative (O3/O2) stress induced tumor remission. Our aim
      was to evaluate candidate genes associated with tumor regression. MATERIALS AND
      METHODS: For identification of tumor remission-related genes, microarray analysis
      was performed with subsequent validation by polymerase chain reaction (PCR), in
      situ hybridization, immunohistochemistry and western blot analysis. RESULTS:
      Microarray analysis indicated a prominent reduction of epidermal growth factor
      receptor (Egfr, Erbb1) expression levels in regressing tumors. Quantitative PCR
      confirmed a significant (p<0.005) down-regulation of Erbb1-3 mRNA in regressing
      VX2 tumors. Histological localization of Erbb1-3 mRNA transcript and protein
      indicated reduced Erbb gene expression occurring at the level of individual VX2
      tumor cells rather than solely being an effect of tumor shrinkage. This study
      highlights changes in the Erbb gene signature of regressing VX2 carcinomas as a
      predictor for therapy response. The VX2 carcinoma animal model, therefore,
      appears suitable for the identification and evaluation of new diagnostic,
      prognostic and therapeutic biomarkers prior to their application in patients with
      HNSCC.

PMID- 30194152
TI  - Trichomonas Vaginalis Inhibits HeLa Cell Growth Through Modulation of Critical
      Molecules for Cell Proliferation and Apoptosis.
AB  - BACKGROUND/AIM: Cervical cancer is one of the deadliest gynecological cancers in
      USA. The role of Trichomonas Vaginalis (T. Vag) in the etiology or pathogenesis
      of cervical cancer is still poorly understood and controversial. MATERIALS AND
      METHODS: Clonogenic assay, PCNA staining, TUNEL staining and caspase-3 activity
      assay were used to investigate the direct in vitro effect of T. Vag on human
      cervical cancer by using HeLa cells. We further investigated the potential
      molecular mechanisms using RT-PCR and immunohistochemical staining. RESULTS: We
      found that culture supernatant of T. Vag inhibited growth of HeLa cervical cancer
      cells and this correlated with up-regulation of p15. We also found that culture
      supernatant of T. Vag induced apoptosis of HeLa cells and this correlated with up
      regulation of Fas, TRAIL and TRAILR1. CONCLUSION: Culture supernatant of T. Vag
      inhibits growth of HeLa cervical cancer cells by inhibition of proliferation and
      promotion of apoptosis. Our study might be helpful to address the association
      between the development of cervical cancer and infection of T. Vag.

PMID- 30194153
TI  - The Plasma Levels of the Angiogenic Cytokine Endocan Are Elevated in Patients
      with Multiple Myeloma.
AB  - BACKGROUND/AIM: Monoclonal gammopathy of unknown significance (MGUS) and
      smoldering multiple myeloma often precede multiple myeloma (MM). The
      identification of biomarkers predicting progression to MM might facilitate an
      earlier diagnosis of MM. Our study assessed the diagnostic value of plasma levels
      of endocan, a 50-kDa soluble dermatan sulfate proteoglycan produced and secreted
      by endothelial cells, hitherto unknown in MM, in patients with plasma cell
      dyscrasia. MATERIALS AND METHODS: Endocan levels were determined in 96 peripheral
      blood plasma samples by sandwich enzyme-linked immunosorbent assay (ELISA) in
      healthy controls (n=12), in patients with MGUS (n=17), and in patients newly
      diagnosed with (n=42) or relapsed/refractory (n=25) MM. RESULTS: Median endocan
      concentration increased from MGUS (315.00 pg/ml) and healthy controls (316.19
      pg/ml) to newly-diagnosed MM (371.82 pg/ml; p=0.027). The low endocan levels
      (median=246.20 pg/ml) in patients with relapsed/refractory MM were similar to
      those in healthy controls and patients with MGUS. A cut-off value of >220 pg/ml
      endocan in peripheral blood discriminated patients newly diagnosed with MM from
      those with MGUS (area under the curve(AUC)=0.66, 95% confidence interval(CI)=0.55
      0.81). CONCLUSION: The plasma levels of endocan can non-invasively differentiate
      patients newly diagnosed with MM from those with MGUS and should therefore be
      evaluated prospectively as a potential diagnostic marker.

PMID- 30194154
TI  - AS602801, an Anti-Cancer Stem Cell Drug Candidate, Suppresses Gap-junction
      Communication Between Lung Cancer Stem Cells and Astrocytes.
AB  - BACKGROUND/AIM: Cancer stem cells (CSCs) are associated with tumorigenesis,
      recurrence, and metastasis. Cell-cell communication via gap junctions (GJs)
      between metastatic cancer cells and astrocytes is necessary for brain metastasis.
      Agents targeting communication between CSCs and astrocytes are expected to
      suppress brain metastasis. MATERIALS AND METHODS: Using the A549 CSC, a cancer
      stem-like cell derived from A549, we examined the effect of AS602801, an anti
      cancer stem cell agent whose safety has been confirmed in a phase 2 clinical
      trial, on GJ communication and connexin expression using a dye-transfer assay and
      immunoblot analysis, respectively. RESULTS: AS602801 specifically suppressed cell
      cell communication in A549 CSCs without any suppression of GJ communication in
      astrocytes; it also decreased the expression of connexin 43, a constituent of
      GJs, in A549 CSCs. CONCLUSION: The anti-cancer stem cell agent, AS602801, is a
      potential drug candidate against brain metastasis.

PMID- 30194155
TI  - Low Doses of the Anti-psychotic Drug Aripiprazole Have Strong P-gp-inhibitory
      Activity and Sensitize Anti-mitotic Drug-resistant Cancer Cells.
AB  - BACKGROUND/AIM: The present study was designed to identify conditions that would
      increase the sensitivity of resistant cancer cells to anti-mitotic drugs.
      MATERIALS AND METHODS: Previously, we showed that KBV20C cancer cells highly
      resistant to Halaven(r) (HAL) were sensitized by co-treatment with fluphenazine
      (FLU). In this study, we found that low doses of aripiprazole (ARI), another
      antipsychotic drug, sensitized HAL-resistant KBV20C cancer cells. We then
      investigated the mechanisms and roles of ARI in the sensitization of HAL-treated
      KBV20C cancer cells. RESULTS: First-generation P-glycoprotein (P-gp) inhibitor
      verapamil required a dose that was nearly four-fold higher than that of ARI for P
      gp inhibition, which suggested that ARI had a high specificity for P-gp binding
      to prevent efflux of anti-mitotic drugs. ARI was also found to sensitize HAL
      treated KBV20C cells at a low dose, approximately 4-fold lower than that of
      verapamil. Co-treatment of ARI with another anti-mitotic drug, vincristine, also
      increased the sensitization of KBV20C cells. ARI caused a reduction in cell
      viability, increased G2 arrest, and up-regulated expression of the DNA damage
      protein, pH2AX, when co-treated with HAL. Moreover, G2 phase arrest and apoptosis
      in HAL-ARI co-treated cells resulted from the up-regulation of retinoblastoma
      protein, reduced extracellular signal-regulated kinase pathway activity, and down
      regulation of cell division cyclin protein. CONCLUSION: Cancer cells that are
      highly resistant to HAL can be sensitized with the antipsychotic drug, ARI, which
      exerts specific P-gp inhibitory effects at a low dose.

PMID- 30194156
TI  - Inhibition of Human Neuroblastoma Cell Proliferation by N-acetyl-L-cysteine as a
      Result of Increased Sulfane Sulfur Level.
AB  - BACKGROUND/AIM: In various cancer cells, the level of sulfane sulfur-containing
      compounds is decreased compared to normal cells. In the present study the effect
      of N-acetyl-L-cysteine (NAC), which acts as a precursor of H2S synthesis, on the
      human neuroblastoma SH-SY5Y cell proliferation, the activity of 3
      mercaptopyruvate sulfurtransferase (MPST), and the level of sulfane sulfur were
      investigated. MATERIALS AND METHODS: SH-SY5Y cells were treated with NAC, while
      untreated cells were used as the control. The toxicity of NAC on the cells was
      studied by the LDH cytotoxicity assay; cell proliferation was examined by the MTT
      method. MPST activity and sulfane sulfur level were also analyzed in the NAC
      treated cells. RESULTS: The addition of NAC to the medium, in non-cytotoxic
      concentrations, resulted in inhibition of the SH-SY5Y cell proliferation after 48
      h of culture. The MPST activity and the level of sulfane sulfur-containing
      compounds were also elevated under the same culture conditions. CONCLUSION: The
      antiproliferative activity of NAC in the SH-SY5Y cells was associated with an
      increase in the MPST activity and consequently with an increase in the
      intracellular level of sulfane sulfur in these cells.

PMID- 30194157
TI  - Antiproliferative and Apoptotic Role of Novel Synthesized Cu(II) Complex with 3
      (3-(4-fluorophenyl)Triaz-1-en-1-yl) Benzenesulfonamide in Common Cancer Models.
AB  - BACKGROUND/AIM: Chemotherapeutic treatment options are often ineffective due to
      the development of resistance in cancer cells. Therefore, developing new anti
      cancer agents is crucial for cancer treatment. Some triazine derivatives, their
      complexes and Copper(II) have anti-cancer effects on cancer cells. In this study,
      we aimed to determine the anti-proliferative effect of the novel synthesized
      Cu(II) complex with 3-(3-(4-fluorophenyl)triaz-1-en-1-yl) benzene-sulfonamide
      compound on the common cancer cell lines HeLa, MDA-MB-231, A2780 and MCF7.
      MATERIALS AND METHODS: Common cancers cell lines were treated with copper
      complexes. Cell viability and apoptotic gene expression were examined. RESULTS:
      Novel synthesized copper complex led to decreased viability of all cell lines. It
      also induced apoptosis via increasing the expression of caspase-3, caspase-9, Bax
      and p53 proteins and decreasing ERK expression. CONCLUSION: The novel synthesized
      copper complex has a significant inhibitory effect on the viability of cancer
      cell lines and can be considered as an antitumor agent for further studies.

PMID- 30194158
TI  - Seminal Cell Free DNA Concentration Levels Discriminate Between Prostate Cancer
      and Benign Prostatic Hyperplasia.
AB  - BACKGROUND/AIM: Seminal plasma cfDNA (scfDNA) was recently proposed as a novel
      PCa biomarker. Our aim was to evaluate whether scfDNA could discriminate PCa from
      benign prostate hyperplasia (BPH) patients. PATIENTS AND METHODS: A cohort of 43
      patients (18 and 25 pathology proven PCa and BPH patients), and 13 healthy age
      matched control subjects were enrolled. scfDNA quantification was performed. Data
      were analyzed through ANOVA testing. RESULTS: Average scfDNA concentrations were
      1,407.83 ng/MUl, 128.13 ng/MUl and 78.09 ng/MUl for PCa patients, BPH patients
      and healthy subjects, respectively. Statistical analysis showed a significant
      difference among the groups, allowing for distinction of patients with optimal
      accuracy. A cut-off level of 450 ng/MUl scfDNA was identified for the
      differentiation of PCa and BPH patients. CONCLUSION: scfDNA concentrations are
      significantly different between PCa patients and BPH patients. scfDNA is a
      promising biomarker with several applications in PCa diagnosis, screening
      programs and therapeutic monitoring.

PMID- 30194159
TI  - Prognostic Value of Serum Creatinine Levels in Patients with Epithelial Ovarian
      Cancer.
AB  - AIM: To evaluate preoperative serum creatinine level as a prognostic parameter in
      patients with primary epithelial ovarian cancer (EOC). PATIENTS AND METHODS: In a
      retrospective cohort study, serum levels of creatinine were evaluated in 498
      patients with EOC. Data were extracted from our prospectively maintained
      database. Results were correlated with clinicopathological parameters and patient
      survival. RESULTS: The mean pre-therapeutic serum creatinine level in patients
      with EOC was 0.84+/-0.40 mg/dI. A serum creatinine level of 1.2 mg/dl or higher
      was found in 22 (4.4%) patients and associated with poor survival. In a
      multivariate logistic regression analysis, the serum creatinine level was a
      significant independent prognostic parameter of overall survival. CONCLUSION: The
      preoperative serum level of creatinine may be useful as an additional independent
      prognostic parameter in patients with EOC.

PMID- 30194160
TI  - Differential Mechanism of Action of 3,4',7-O-trimethylquercetin in Three Types of
      Ovarian Cancer Cells.
AB  - BACKGROUND/AIM: 3,4',7-O-trimethylquercetin (34'7TMQ), a derivative of quercetin,
      inhibited ovarian cancer cell migration and invasion without affecting
      proliferation. In this study, the apoptotic effect of 34'7TMQ on three cancer
      cell lines (CRL-1978, CRL-11731, SK-OV-3) was evaluated. MATERIALS AND METHODS:
      Expression of pro-apoptotic proteins such as Bax/Bcl-2 ratio, p38 MAP kinase, and
      caspase-9 were measured by western blot analysis. Annexin-V staining was
      performed to visualize apoptotic signaling. RESULTS: Caspase-9 was up-regulated
      in all three cell lines. Bax/Bcl-2 ratio was up-regulated in CRL-1978 and SK-OV-3
      but down-regulated in CRL-11731. The p38 MAPK was down-regulated in CRL-1978, up
      regulated in SK-OV-3, and had differential expression in CRL-11731. Annexin V
      staining indicated that 34'7TMQ at 6.25 MUM induced apoptotic signaling in the
      CRL-1978 ovarian cancer cell line. CONCLUSION: 34'7TMQ induced apoptosis in three
      types of cancer cell lines but it appears to have a different mechanism of action
      in each cell line.

PMID- 30194161
TI  - Extracellular Vesicles Derived from Hypoxic Colorectal Cancer Cells Confer
      Metastatic Phenotype to Non-metastatic Cancer Cells.
AB  - BACKGROUND/AIM: Tumor-secreted extracellular vesicles (EVs) play an important
      role as mediators of intercellular communication. Hypoxia is a common feature of
      solid tumors frequently associated with an aggressive clinical behavior. This
      study aimed to gain a deeper understanding into the functions of EVs in
      intercellular communication between primary and metastatic cancer cells under
      hypoxic conditions. MATERIALS AND METHODS: EVs were isolated from two isogenic
      colorectal cancer (CRC) cell lines SW480 and SW620 cultured under normoxic and
      hypoxic conditions. Their uptake and effects in SW480 and SW620 cells were
      studied using EV uptake, proliferation, spheroid-formation, wound healing and
      invasion assays. RESULTS: Our data showed that hypoxia enhanced the release of
      EVs from CRC cells in a Hypoxia Induced Factor (HIF)-1-dependent manner. Hypoxic
      EVs were taken up by CRC cells more efficiently than normoxic EVs. Hypoxic EVs
      stimulated motility, invasiveness and stemness of primary tumour-derived SW480
      cells, whereas they had a little effect on metastasis-derived SW620 cells.
      CONCLUSION: Hypoxic colorectal cancer-derived EVs confer aggressiveness and
      invasiveness to hypoxia-naive cancer cells.

PMID- 30194162
TI  - Aging-related Repositioned Drugs, Donepezil and Sildenafil Citrate, Increase
      Apoptosis of Anti-mitotic Drug-resistant KBV20C Cells Through Different Molecular
      Mechanisms.
AB  - BACKGROUND/AIM: The study focused on identifying the mechanisms or drugs that
      could sensitize P-glycoprotein (P-gp)-overexpressing resistant KBV20C cancer
      cells to halaven (HAL) or vincristine (VIC) treatment. MATERIALS AND METHODS:
      Based on the relatively low dose or IC50 values for sensitizing anti-mitotic drug
      resistant KBV20C cells, the aging-related drugs donepezil (DON) and sildenafil
      citrate (SID) were selected. Fluorescence-activated cell sorting (FACS), western
      blotting, and annexin V analyses were performed to investigate the mechanism of
      action of DON and SID in HAL-treated KBV20C cells. RESULTS: DON or SID reduced
      cell viability, increased G2 arrest, and up-regulated the expression of the DNA
      damaging protein pH2AX when used as co-treatment with HAL. DON and SID induced
      both early and late apoptosis in KBV20C cells in response to HAL treatment,
      without increasing autophagy. VIC-DON and VIC-SID co-treatments increased
      sensitization of KBV20C cells, suggesting that DON and SID can be combined with
      other anti-mitotic drugs for sensitizing resistant cancer cells. When the
      sensitization efficacies of DON and SID were compared to that of the anti
      psychotic repositioned drug fluphenazine (FLU), HAL-SID or HAL-FLU co-treatments
      were found to have better sensitization effects than HAL-DON suggesting that HAL
      SID sensitization mechanism is different from that of HAL-DON. In addition, DON
      was found to have higher P-gp inhibitory activity than FLU or SID. CONCLUSION:
      These results suggest that HAL-FLU or HAL-SID sensitization in KBV20C cells
      involves both cytotoxic and P-gp inhibitory effects, whereas HAL-DON
      sensitization may involve only P-gp inhibitory activity of DON.

PMID- 30194163
TI  - Association of Matrix Metalloproteinase-8 Genotypes with the Risk of Bladder
      Cancer.
AB  - BACKGROUND/AIM: Matrix metalloproteinases (MMPs) control the homeostasis of the
      extracellular matrix and their genetic polymorphisms may contribute to cancer
      susceptibility. The aim of this study was to reveal the genotypes of MMP8 among
      the Taiwanese and examine the contribution of MMP8 C-799T, Val436Ala and
      Lys460Thr polymorphisms to bladder cancer. MATERIALS AND METHODS: MMP8 C-799T,
      Val436Ala and Lys460Thr polymorphic genotypes were determined in 375 patients
      with bladder cancer and 375 healthy controls by polymerase chain reaction
      restriction fragment length polymorphism methodology. RESULTS: Regarding MMP8 C
      799T, there was no significant differential distribution between patient and
      control groups [p for trend=0.6629]. The odds ratios (ORs) after adjusting for
      age, gender, smoking and alcohol drinking status for those carrying CT and TT
      genotypes at MMP8 C-799T were 1.13 (95%CI=0.89-1.44, p=0.3688) and 1.10
      (95%CI=0.87-1.52, p=0.9030), respectively, compared to those carrying the wild
      type CC genotype. Regarding MMP8 Val436Ala, there was no significant differential
      distribution between patient and control groups [p for trend=0.8166]. The
      adjusted OR for those carrying AC and CC genotypes at MMP8 Val436Ala were 0.71
      (95%CI=0.31-2.28, p=0.6094) and 1.00 (95%CI=0.21-4.73, p=0.7247), respectively.
      The polymorphism Lys460Thr at MMP8 was not found among Taiwanese patients.
      CONCLUSION: MMP8 C-799T, Val436Ala and Lys460Thr may only play an indirect role
      in determining personal cancer susceptibility for bladder cancer in Taiwan.

PMID- 30194164
TI  - Benzyl Isothiocyanate Induces Apoptotic Cell Death Through Mitochondria-dependent
      Pathway in Gefitinib-resistant NCI-H460 Human Lung Cancer Cells In Vitro.
AB  - BACKGROUND/AIM: Gefitinib is used to treat patients with lung cancer, but in some
      patients, the disease becomes gefitinib-resistant. Benzyl isothiocyanate (BITC),
      found in cruciferous vegetables, has shown anticancer activity in many human
      cancer cell lines. However, the effects of BITC on gefitinib-resistant NCI-H460
      lung cancer cells in vitro have not been investigated. MATERIALS AND METHODS: The
      effects of BITC on gefitinib-resistant NCI-H460 lung cancer cells were
      investigated in vitro. Flow cytometric assay was used for determining the total
      viable cell number, apoptotic cell death, the production of reactive oxygen
      species (ROS) and Ca2+, mitochondriaI membrane potential (Psim) and caspase-3, -8
      and -9 activities. Furthermore, 4', 6-diamidino-2-phenylindole staining was used
      to examine chromatin condensation in NCI-H460 and NCI-H460/G cells. RESULTS: BITC
      reduced total viable cell number via the induction of apoptotic cell death, that
      was also confirmed by annexin V/propidium iodide double staining assay. BITC
      increased ROS and Ca2+ production, reduced Psim and increased caspase-3, -8 and 
      9 activities in both NCI-H460 and NCI-H460/G cells. Western blotting assay also
      showed that BITC increased expression of cleaved caspase-3 and -9, cytochrome c,
      BCL2-associated X protein, endonuclease G, poly (ADP-ribose) polymerase, growth
      arrest and DNA-damage protein 153, caspase-7 and activating transcription factor
      6 alpha, but reduced apoptosis-inducing factor and caspase-9, BH3-interacting
      domain death agonist, calpain 1, glucose-regulated protein 78 and inositol
      requiring enzyme 1 alpha in NCI-H460/G cells. CONCLUSION: BITC-induced apoptotic
      cell death appears to occur via caspase- and mitochondria-dependent pathways in
      both cell lines.

PMID- 30194165
TI  - SNX-2112 Induces Apoptosis and Autophagy of Nara-H Cells.
AB  - BACKGROUND/AIM: Selective heat shock protein 90 (Hsp90) inhibitor SNX-2112
      exhibits antitumor activity in multiple cancer cell types. Here, the antitumor
      activity of SNX-2112 in Nara-H cells was analyzed. MATERIALS AND METHODS:
      Antitumor activity of SNX-2112 was assessed using a cell proliferation assay. We
      also examined the signalling pathways involved in SNX-2112-mediated autophagy and
      apoptosis of Nara-H cells by western blot and morphological analyses. RESULTS:
      Cell proliferation assays demonstrated that SNX-2112 inhibited Nara-H cell
      growth. Western blotting revealed that SNX-2112 induced apoptosis and autophagy,
      inhibited mammalian target of rapamycin (mTOR) phosphorylation, and suppressed
      the mitogen-activated protein kinase (MAPK) signalling pathway. Morphological
      analysis confirmed that SNX-2112 induced autophagy and apoptosis. CONCLUSION: SNX
      2112 induced autophagy and apoptosis of Nara-H cells by inhibiting mTOR and MAPK
      pathways. Our results support developing SNX-2112 to treat human soft tissue
      sarcomas.

PMID- 30194166
TI  - Cell Subpopulations Overexpressing p75NTR Have Tumor-initiating Properties in the
      C6 Glioma Cell Line.
AB  - BACKGROUND/AIM: Glioma is the most common and lethal primary brain tumor. Even
      with the development of multidisciplinary treatment approaches, results are
      disappointing because of the unavoidable tumor recurrence, which may be caused by
      the existence of tumor-initiating cells. The p75 neurotrophin receptor (p75NTR),
      which belongs to the tumor necrosis factor receptor superfamily, is not only
      involved in various cellular functions but also related to tumor growth. This
      study is focused, on the possible role of p75NTR in glioma tumor initiation.
      MATERIALS AND METHODS: C6 cells with high and low expression of p75NTR were
      sorted using flow cytometry. The neurosphere characteristics and properties of
      these two subpopulations were assessed and compared with those of parental cells.
      Radiation and chemotherapy sensitivity was also analyzed in these cell
      populations. Finally, in vivo tumorigenicity of cells was tested in a rat model.
      RESULTS: Cells overexpressing p75NTR (C6p75+++ cells) demonstrated greater
      ability of neurosphere formation, colony proliferation, and certain stem cell
      marker overexpression than cells with low p75NTR expression (C6p75+) and parental
      cells. In addition, following irradiation or temozolomide treatment, more viable
      C6p75+++ cells remained, and they proliferated into more colonies. In vivo,
      C6p75+++ cell implantation in Sprague Dawley rats reduced the survival time.
      CONCLUSION: Cells with p75NTR overexpression demonstrated certain unique
      characteristics of tumor-initiating cells, such as neurosphere formation, high
      colony proliferation, and resistance to radio- and chemotherapy. With regard to
      the heterogeneous composition of glioma cells, p75NTR can be used as an
      alternative marker to identify a glioma subpopulation with tumor-initiating
      properties.

PMID- 30194167
TI  - Potential Oncogenic Role and Prognostic Implication of MicroRNA-155-5p in Oral
      Squamous Cell Carcinoma.
AB  - BACKGROUND: Altered microRNA expression is associated with cancer progression.
      This study investigated the prognostic significance of microRNA-155-5p (miR-155
      5p), a well-known oncomiR, in oral squamous cell carcinoma (OSCC). MATERIALS AND
      METHODS: miR-155-5p expression was assessed using quantitative reverse
      transcription polymerase chain reaction in 68 formalin-fixed, paraffin-embedded
      OSCC specimens. E-Cadherin immunohistochemistry was conducted to correlate
      epithelial-mesenchymal transition (EMT) with miR-155-5p expression. RESULTS:
      Elevated miR-155-5p was associated with higher pathological TNM stage (p=0.048)
      and relapse (p=0.029). High miR-155-5p expression, along with angiolymphatic
      invasion and advanced stage, was a statistically significant prognostic factor
      for poorer disease-free survival. In patients with stage I-II disease, high miR
      155-5p was the only significant prognostic factor (p=0.033). A significant
      negative correlation was observed between miR-155-5p and E-cadherin expression
      (p=0.015), suggesting a possible role for miR-155-5p in EMT. CONCLUSION: miR-155
      5p expression might contribute to EMT-associated OSCC progression and serve as a
      biomarker for predicting relapse, especially for patients with early-stage OSCC.

PMID- 30194168
TI  - Fluoxetine Inhibits DNA Repair and NF-KB-modulated Metastatic Potential in Non
      small Cell Lung Cancer.
AB  - BACKGROUND/AIM: The aim of present study was to verify the effect of fluoxetine
      on DNA repair and metastatic potential in non-small cell lung cancer (NSCLC) in
      vitro. MATERIALS AND METHODS: Highly metastatic NSCLC CL1-5-F4 cells were used in
      this study. Cells were treated with different concentrations of fluoxetine or QNZ
      (NF-KB inhibitor) for 48 h. After treatment, cell viability, apoptotic signaling,
      NF-KB activation, expression of DNA repair and metastasis-associated proteins,
      and cell migration/invasion were evaluated by (4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium assay, flow cytometry, NF-KB reporter gene, western blotting,
      and cell migration/invasion assay, respectively. RESULTS: Fluoxetine induced
      apoptosis and reduced cell viability, NF-KB activation, expression of DNA repair
      and metastasis-associated proteins, and cell migration/invasion in CL1-5-F4
      cells. Also, NF-KB activation was the critical factor in fluoxetine-inhibited
      metastatic potential. CONCLUSION: Fluoxetine induced apoptosis and inhibited DNA
      repair and metastatic potential in NSCLC CL1-5-F4 cells.

PMID- 30194169
TI  - Biomarkers of Oxidative Stress Associated with the Risk of Potentially Malignant
      Oral Disorders.
AB  - AIM: To investigate the effect of oxidative stress biomarkers on the risk of
      potentially malignant oral disorders (PMODs). MATERIALS AND METHODS: A total of
      208 male adults with PMODs and an equal number of same-age control patients were
      enrolled. Plasma biomarkers of oxidative stress, measured with 8-hydroxy-2'
      deoxyguanosine (8-OHdG) and 8-isoprostane (8-ISO), were determined using enzyme
      linked immunosorbent assay (ELISA) kits. PMODs were diagnosed in accordance with
      the World Health Organization (WHO) guidelines. RESULTS: A significant
      association between a high level of 8-ISO and an increased risk of PMODs was
      identified [odds ratio (OR)=1.71, 95% confidence interval (CI)=1.12-2.63;
      p=0.013]. This positive association was stronger among patients with PMOD subtype
      of leukoplakia (OR=1.94, 95% Cl=1.24-3.06; p=0.004). However, no significant
      association was observed between plasma 8-OHdG levels and overall risk of PMODs
      or subtypes. CONCLUSION: Increased plasma 8-ISO levels may indicate the
      prominence of lipid peroxidation in the development of PMODs, particularly
      leukoplakia.

PMID- 30194170
TI  - Shift of Keratin Expression Profile in End-stage Kidney Increases the Risk of
      Tumor Development.
AB  - BACKGROUND/AIM: Pre-neoplastic lesions and renal cell tumors of distinct pheno-
      and genotypes occur frequently in end-stage kidneys. The aim of this study was to
      investigate the role of KRT7 and KRT19 in this process, the expression of which
      was previously detected by Affymetrix GeneChip analysis. PATIENTS AND METHODS:
      Twelve end-stage kidneys were analyzed to find pre-neoplastic lesions and tumors
      and expression of KRT7 and KRT19 was examined by immunohistochemistry. RESULTS: A
      total of 17 tumors, 149 pre-neoplastic lesions, 179 simple or proliferative cysts
      >2 mm were identified. Diffuse expression of KRT7 and KRT19 was seen in all end
      stage kidneys as well as in the vast majority of cysts, pre-neoplastic lesions
      and tumors. CONCLUSION: Our data indicates that de novo expression of KRT7 and
      KRT19 resulting in altered plasticity and stem cell characteristics of epithelial
      cells might be a crucial factor in increasing the risk of tumor development in
      end-stage kidneys.

PMID- 30194171
TI  - Studies of Correlations Between Single Nucleotide Polymorphisms of DNA Repair
      Genes and Endometrial Cancer in Polish Women.
AB  - AIM: The goals of this study included an analysis of the incidence of single
      nucleotide polymorphisms (SNPs) genotypes and alleles in DNA repair genes and
      evaluation of the effects by which this genetic variability may influence the
      risk for endometrial cancer. MATERIALS AND METHODS: The study group included 610
      women with endometrial cancer and was compared with a quantitatively matched
      control group of 610 women without any diagnosed malignancy. The following
      polymorphisms were analyzed: X-Ray repair cross complementing 1 (XRCC1)-Arg399Gln
      (rs25487); XRCC2-Arg188His (rs3218536); XRCC3-Thr241Met (rs861539); ERCC excision
      repair 2, TFIIH core complex helicase subunit (ERCC2)-Lys751Gln (rs13181); and 8
      oxoguanine DNA glycosylase (OGG1)-Ser326Cys (rs13181). RESULTS: Allele XRCC2
      188His [odds ratio (OR)=5.24, 95% confidence interval (CI)=4.36-6.29; p<0.0001],
      hOGG1-326Cys (OR=1.60, 95% CI=1.36-1.88; p<0.0001) and ERCC2-751Gln (OR=1.67, 95%
      CI=1.42-1.96; p<0.0001) strongly correlated with neoplastic disease. CONCLUSION:
      The evaluated SNPs may be approached as a group of new risk factors for the
      development of this cancer type.

PMID- 30194172
TI  - Efficacy and Safety Data of Osimertinib in Elderly Patients with NSCLC Who Harbor
      the EGFR T790M Mutation After Failure of Initial EGFR-TKI Treatment.
AB  - BACKGROUND/AIM: The aim of this study was to evaluate the safety and efficacy of
      osimertinib for elderly patients, since the data remain limited. PATIENTS AND
      METHODS: A total of 77 patients with advanced non-small cell lung cancer (NSCLC)
      harboring the epidermal growth factor receptor (EGFR) T790M mutation and treated
      with osimertinib were reviewed. Efficacy and safety indicators, such as EGFR
      tyrosine kinase inhibitor (TKI)-related adverse events (AEs) and osimertinib
      associated hematotoxicity, were evaluated in elderly patients (elderly group, EG;
      age, >=75 years) by comparing them with younger patients (non-EG; aged <75
      years). The frequency of AEs associated with osimertinib was compared with the
      initial EGFR-TKI treatment before osimertinib administration in the same patient
      cohort. RESULTS: Of the total 77 patients, 18 (23%) were assigned to the EG,
      whereas 59 (77%) were assigned to the non-EG. There were no significant
      differences in overall response rate and progression-free survival between the
      two groups. Regarding the safety of osimertinib, the EG had significantly more
      grade >=2 paronychia than the non-EG (16.6% vs. 1.6%, p=0.04). Additionally, the
      maximum grade of EGFR-TKI-related AEs associated with osimertinib in the EG was
      significantly lower than that of the initial EGFR-TKI treatment (p=0.03).
      CONCLUSION: Osimertinib is a safe and effective treatment option for elderly
      patients with advanced NSCLC who harbor the EGFR mutation.

PMID- 30194173
TI  - Impact of Interval Between Neoadjuvant Chemoradiation and Surgery Upon Morbidity
      and Survival of Patients with Squamous Cell Carcinoma of Thoracic Esophagus.
AB  - BACKGROUND/AIM: The present study aimed to determine the effects of intervals
      between neoadjuvant chemoradiotherapy (nCRT) and esophagectomy on therapeutic
      outcomes in patients with locally advanced esophageal squamous cell carcinoma
      (ESCC). PATIENTS AND METHODS: We analyzed data from 134 consecutive patients who
      were diagnosed with locally advanced ESCC of the thoracic esophagus and were
      treated by nCRT followed by esophagectomy between September 2003 and September
      2015. We assigned the patients to groups A and B according to whether they
      underwent esophagectomy <=8 or >8 weeks after nCRT. RESULTS: The two groups were
      comparable in terms of age, gender, performance status, comorbidities, tumor
      location, clinical stage, R0 resection rates and pathological responses to nCRT.
      The incidences of pneumonia and respiratory failure were significantly higher in
      group B (p=0.03, p=0.009, respectively). Recurrence-free (RFS) and overall (OS)
      survival rates did not significantly differ between the two groups. However, RFS
      was significantly poorer among patients with R0 resection (p=0.04) and those of
      cStages III and IV (p=0.009) in group B. CONCLUSION: Esophagectomy should proceed
      within eight weeks after nCRT from the viewpoints of respiratory morbidity and
      impact of RFS on patients with R0 resection.

PMID- 30194174
TI  - Screening Patients with Esophageal Cancer to Determine Eligibility for Adjuvant
      Treatment Trials.
AB  - BACKGROUND: The tolerability of adjuvant chemotherapy in esophageal cancer is
      unclear. PATIENTS AND METHODS: This was a phase II trial of adjuvant paclitaxel
      in patients with esophageal cancer after trimodality treatment. Patients with
      residual viable tumor after resection were eligible for study inclusion.
      Treatment was 80 mg/m2 paclitaxel intravenously on days 1, 8, and 15 every 28
      days for total of two cycles. The primary objective was to determine whether 75%
      or more of the patients would tolerate 240 mg/m2 or more of paclitaxel, which
      corresponded to 50% or more of the total planned dose. RESULTS: Eleven out of the
      12 enrolled patients (92%, 95% confidence interval (CI)=62-100%) were able to
      complete at least 50% of the planned paclitaxel dose. Median progression-free
      survival was 7 months (95% CI=2-28 months). Median overall survival was 28 months
      (95% CI=12-36 months). Only one patient experienced a grade 4 adverse event.
      CONCLUSION: Screening patients with esophageal cancer after trimodality treatment
      might improve completion of adjuvant trials.

PMID- 30194175
TI  - Radiation Therapy for Positive Surgical Margins in Women >=70 Years with Stage I,
      Estrogen Receptor-positive Breast Cancer.
AB  - BACKGROUND/AIM: A re-excision for positive margin(s) following a lumpectomy for
      invasive breast cancer is a standard recommendation. However, for elderly women
      with stage I estrogen receptor-positive (ER+) tumors, who may be at higher
      surgical risk, whether radiation therapy without re-excision will be adequate is
      not known. PATIENTS AND METHODS: We evaluated a cohort of 53,950 women aged >=70
      years with Stage I, ER+ breast cancer who had lumpectomy and anti-hormone therapy
      diagnosed between 2004 and 2011 in the National Cancer Data Base. Patients were
      divided into four groups: 1) negative margins without radiation (XRT), 2)
      negative margins with XRT, 3) positive margins without XRT, and 4) positive
      margins with XRT. Clinicopathological and sociodemographic variables were
      compared among these groups. Univariable and multivariable analysis were
      employed. RESULTS: The 5-year overall survival (OS) rates for the groups were as
      follows: 1) negative margins without radiation (XRT); 77.1%, 2) negative margins
      with XRT; 90.0%, 3) positive margins without XRT; 62.9%, and 4) positive margins
      with XRT; 86.8% (p<0.0001). Significant predictors (p<0.01) of OS include
      treatment groups, age, income status, facility type, facility location, tumor
      size, tumor grade, and comorbidities. CONCLUSION: Radiation therapy for positive
      surgical margins without re-excision may be a viable option for elderly women
      with stage I, ER+ tumor treated with lumpectomy and hormonal therapy.

PMID- 30194176
TI  - Prophylactic Cranial Irradiation for Patients with Small Cell Lung Cancer in
      Germany: Pattern of Care Survey.
AB  - BACKGROUND/AIM: The general pattern of care regarding the application of
      prophylactic cranial irradiation (PCI) in small cell lung cancer (SCLC) patients
      in Germany has not been previously evaluated. This survey was conducted to assess
      patterns of care. PATIENTS AND METHODS: Radiation oncology institutions in
      Germany were surveyed via an anonymous online questionnaire sent by e-mail to
      member institutions of the German Society for Radiation Oncology. RESULTS: A
      total of 95 responses were received (29% response rate). Eighty-eight percent of
      all responders recommended a PCI total dose of 30Gy delivered in 15 daily
      fractions. Overall, 11 and 38% of the respondents applied PCI simultaneously with
      chemo- and radiotherapy, respectively. A quarter of respondents offered
      hippocampal-avoidance PCI and followed their patients with serial brain imaging.
      CONCLUSION: PCI with a total dose of 30 Gy in 15 daily fractions, without
      neuropsychological testing and hippocampus-avoidance, delivered after completion
      of primary multimodal treatment remains standard in Germany.

PMID- 30194177
TI  - Neoadjuvant Chemotherapy with Docetaxel, Cisplatin and S-1 for Resectable
      Advanced Esophageal Cancer.
AB  - BACKGROUND/AIM: Although the efficacy is limited, standard therapy for Stage
      II/III esophageal cancer in Japan includes neoadjuvant chemotherapy with
      cisplatin plus 5-fluorouracil. A phase II trial was conducted on patients with
      resectable advanced esophageal cancer obtaining neoadjuvant chemotherapy with
      docetaxel, cisplatin plus S-1 (DCS). PATIENTS AND METHODS: A total of 40 patients
      were enrolled, each treated by the following DCS regimen: docetaxel 40 mg/m2,
      cisplatin 60 mg/m2 on day 1, and S-1 80 mg/m2 on days 1-14, repeated every four
      weeks, for a maximum of three cycles. RESULTS: Clinical response rate was 76% and
      the pathological response rate (Grade 2/3) was 33%. Hematological toxicities of
      Grade 3/4 were leukopenia 50%, neutropenia 68%, and febrile neutropenia 18%.
      CONCLUSION: Neoadjuvant chemotherapy with DCS is a feasible therapeutic strategy
      for patients with advanced thoracic esophageal squamous cell carcinoma.

PMID- 30194178
TI  - Synovial Sarcoma of the Thyroid Gland, Diagnostic Pitfalls and Clinical
      Management.
AB  - BACKGROUND/AIM: Synovial sarcoma is a soft tissue sarcoma that tends to affect
      young adults. There are few reports on primary synovial sarcoma of the thyroid
      and the aim of this study was to document the clinical and pathological features
      of synovial sarcoma occurring at this site. CASE PRESENTATION: A retrospective
      review of a prospectively maintained database was performed to identify patients
      with synovial sarcoma of the thyroid treated at the Royal Marsden Hospital
      between 2000 and 2017. Five patients were identified that underwent initial
      surgical management of localized disease. The mean age at presentation was 38
      years, and male to female ratio was 4:1. In 3 out of 5 cases, the diagnosis of
      synovial sarcoma was made on the post-operative excision specimen. Two of these
      patients were treated at our institution on the development of metastatic
      disease. We conducted a literature review and identified 12 previously reported
      cases of synovial sarcoma of the thyroid. CONCLUSION: Synovial sarcoma of the
      thyroid is rare and can be challenging to diagnose. The clinical presentation is
      typically indistinguishable from that of thyroid cancer and most cases are
      diagnosed post-operatively on an excision specimen. The clinical and pathological
      features are similar to synovial sarcoma arising at other sites. In our
      experience, the rarity of the diagnosis can lead to difficulty in establishing
      the correct diagnosis and determining the appropriate treatment pathway. It is
      important that physicians are aware of this diagnosis to facilitate prompt
      referral to a specialist centre, for specialist follow-up and treatment which is
      different to the thyroid cancer pathway.

PMID- 30194179
TI  - Influence of Sorafenib, Sunitinib and Capecitabine on the Antioxidant Status of
      the Skin.
AB  - BACKGROUND/AIM: The aim of the present study was to examine the effect of orally
      administered sorafenib (Nexavar(r)), sunitinib (Sutent(r)) and capecitabine
      (Xeloda(r)), which cause palmoplantar erythrodysesthesia (PPE), on the
      antioxidant status of the skin and the formation of free radicals. PATIENTS AND
      METHODS: A total of 42 patients were enrolled, of which 36 (85%) completed the
      study. Overall, 19 received capecitabine (2,000-4,000 mg per day), 10 sunitinib
      (25-50 mg per day) and 7 sorafenib (400-800 mg per day). Cutaneous carotenoids as
      markers of the antioxidant status of the skin were measured 1 day before the
      first oral administration (Tbase) and at day 18 of treatment (T1). RESULTS: The
      mean antioxidant concentrations increased significantly in patients treated with
      sunitinib from 3.99+/-1.01 to 4.68+/-1.32, p=0.047 and sorafenib from 4.83+/-0.74
      to 5.3+/-0.78, p=0.007. Treatment with capecitabine did not significantly
      increase the mean antioxidant concentration. CONCLUSION: Formation of free
      radicals may not be the underlying patho-mechanism of tyrosine kinase inhibitors
      (TKI)- and capecitabine-associated PPE.

PMID- 30194180
TI  - Significance of Additional Gastrectomy Including Endoscopic Submucosal Dissection
      Scar for Gastric Cancer.
AB  - BACKGROUND/AIM: The aim of the study was to evaluate the necessity of gastrectomy
      including endoscopic submucosal dissection (ESD) scar with margin-negative early
      gastric cancer (EGC). PATIENTS AND METHODS: We analyzed 83 patients with EGC who
      received additional gastrectomy after non-curative ESD and evaluated the risk
      factors for residual cancer (RC) and lymph node (LN) metastasis. RESULTS: In
      addition to positive ESD margin, ulceration was a risk factor for RC. Among cases
      with deep submucosal invasion (sm), 3 were diagnosed as having negative margins
      in ESD specimens, but the surgical specimens were positive for cancer. The rate
      of LN metastasis was 12.0%. There was no significant difference in LN metastasis
      between tumor characteristics. CONCLUSION: LN dissection is recommended after non
      curative ESD. Gastrectomy including the ESD scar should be performed not only for
      cases with positive margin in ESD, but also for cases with invasion deeper than
      sm2, even though the margin is negative.

PMID- 30194181
TI  - Radiological Features of IDO1+/PDL1+ Lung Adenocarcinoma: A Retrospective Single
      institution Study.
AB  - AIM: A combination of immune-checkpoint inhibitors that target the programmed
      cell death 1 (PD1)/programmed cell-death ligand 1 (PDL1) pathway and indoleamine
      2,3-dioxygenase 1 (IDO1) is a promising treatment for non-small-cell lung cancer.
      Herein, we investigated clinical features of IDO1+/PDL1+ primary lung
      adenocarcinoma. MATERIALS AND METHODS: IDO1 and PDL1 expression in 388 resected
      primary lung adenocarcinoma samples was evaluated using immunohistochemistry, and
      the radiological features of patients with IDO1+/PDL1+ lung adenocarcinoma were
      analyzed. RESULTS: Of 388 specimens, 229 (59.0%) were IDO1+, 131 (33.8%) were
      PDL1+, and 109 (28.1%) were IDO1+/PDL1+ In multivariate analysis, vascular
      convergence and the absence of surrounding ground glass opacity were
      significantly associated with IDO1+/PDL1+ tumors. Fisher's exact test showed high
      consolidation/tumor ratio was also significantly associated with IDO1+/PDL1+
      tumors. Moreover, maximum standardized uptake in 18F-fluorodeoxyglucose positron
      emission tomography/computed tomography was significantly higher in patients with
      IDO1+/PDL1+ tumors than in those with IDO1- or PDL1- tumors. CONCLUSION:
      IDO1/PDL1 co-expression was significantly related to radiological invasiveness
      and malignancy in lung adenocarcinoma. This study may help select patients likely
      to benefit from combination therapy using immune-checkpoint inhibitors.

PMID- 30194182
TI  - Evaluation of Periodontal Space Widening in Patients with Antiresorptive Drug
      related Osteonecrosis of the Jaws (ARONJ) on Panoramic Radiographs.
AB  - BACKGROUND/AIM: The purpose of this study was to evaluate a potential widening of
      the periodontal space as an initial measurable imaging criterium on panoramic
      radiographs in patients with the diagnosis of antiresorptive drug related
      osteonecrosis of the jaw (ARONJ). PATIENTS AND METHODS: A retrospective analysis
      of panoramic radiographs of 16 patients (12 females and 4 males; mean age is 70.5
      years, standard deviation is 14 years) was performed, over a period of 12 months
      with the diagnosis of ARONJ. Panoramic radiographs of 16 healthy patients (12
      females and 4 males; mean age was 70.6 years, standard deviation was 13.8 years)
      without diagnosis of ARONJ served as controls. All images were taken with the
      same device and were evaluated by two experienced maxillofacial surgeons and one
      dentist. RESULTS: Compared to the control group, a mean widening of the
      periodontal space of 0.06 mm (confidence interval (CI)=0.05-0.17 mm) was found in
      the study group. However, this difference was not statistically significant.
      CONCLUSION: Although a very extensive and sophisticated interindividual
      comparison was performed to evaluate for slight changes of the periodontal space
      in patients with antiresorptive drug therapy, our results demonstrate that PDS
      widening is not a predictive parameter for ARONJ. Therefore, our results indicate
      that panoramic radiographs are not sufficient enough to allow assessment of
      stages and disease progress in ARONJ patients regarding to periodontal space
      widening.

PMID- 30194183
TI  - Are Non-dysplastic Crypts with Corrupted Shapes the Initial Recordable
      Histological Event in the Development of Sporadic Conventional Adenomas?
AB  - BACKGROUND: Colonic crypts with normal epithelial lining displaying corrupted
      shapes (called non-dysplastic crypts with corrupted shapes, NDCs) were earlier
      recorded underneath the adenomatous glands of conventional colon adenomas in
      rats. AIM: To assess the frequency of NDCs in clinical sporadic conventional
      (tubular/villous) adenomas. MATERIALS AND METHODS: NDCs found underneath the
      adenomatous epithelium in 255 sporadic conventional adenomas removed at endoscopy
      were classified into four groups: i) With fission distortions, ii) with length
      distortions, iii) with outline distortions, and iv) with axial polarity
      distortions. In 22 controls, the colonic mucosa proximal or distal to surgically
      removed colonic adenocarcinomas was scrutinized for NDCs. RESULTS: Nearly three
      quarters of the sporadic conventional adenomas investigated here had three or
      more NDCs underneath the adenomatous tissue, those with >=4 NDCs being more
      frequent (46.3%) than those having 1, 2 or 3 NDCs (p<0.05). Nineteen out of the
      22 control colon segments had normal crypts and the remaining three had
      occasional NDCs (mean=3.7, range=2-5). CONCLUSION: NDCs were found underneath the
      adenomatous glands in all 255 sporadic conventional adenomas. Occasionally, NDCs
      were present in the mucosa of the stalk of pediculated conventional adenomas. The
      absence of adenomatous tissue in NDCs of the stalk should rule out the
      possibility that the adenomatous tissue on top had directly orchestrated the
      development of NDCs below. Moreover, NDCs rarely occurred in controls.
      Accordingly, NDCs emerge as a genuine phenomenon of crypt deformation in sporadic
      conventional adenomas. Considering that human colonic crypts typically divide at
      most once or twice during a lifetime, with an average crypt cycle length of 36
      years, the accumulation of NDCs underneath sporadic conventional adenomas is
      remarkable. In light of these considerations, it is suggested that these putative
      mutated NDCs may represent the initial histological recordable event heralding
      the development of sporadic conventional adenomas in the human colon.

PMID- 30194184
TI  - Fibrinogen and Neutrophil-to-lymphocyte Ratio Predicts Survival in Patients with
      Advanced Hypopharyngeal Squamous Cell Carcinoma.
AB  - BACKGROUND/AIM: The purpose of this study is to investigate the prognostic
      significance of the pretreatment F-NLR score, which is based on fibrinogen (F)
      and neutrophil-to-lymphocyte ratio (NLR) in patients with advanced hypopharyngeal
      carcinoma (HPC). MATERIALS AND METHODS: A total of 111 advanced HPC patients
      treated with radiotherapy, chemoradiotherapy, or bioradiotherapy were classified
      into three groups: F-NLR score of 2 (fibrinogen >=341 mg/dl and NLR>=3.59), score
      of 1 (fibrinogen >=341 mg/dl or NLR>=3.59), and score of 0 (fibrinogen <341 mg/dl
      and NLR<3.59). RESULTS: F-NLR score of 2 was an independent prognostic factor for
      overall (OS) and progression-free survival (PFS) in patients with advanced HPC in
      the multivariate analysis. Both OS and PFS were significantly lower in patients
      with an F-NLR score of 2 than in those with an F-NLR score of 0. CONCLUSION: F
      NLR score was useful to stratify patients to extract poor prognostic
      characteristics in patients with advanced HPC.

PMID- 30194185
TI  - Preoperative Low Weight Affects Long-term Outcomes Following Curative Gastrectomy
      for Gastric Cancer.
AB  - BACKGROUND/AIM: A recent nationwide survey using the National Clinical Database
      in Japan identified a high proportion of low-weight patients, who are defined as
      low body mass index (BMI) patients, in comparison with Western countries. This
      study was designed to investigate the influence of low BMI on short- and long
      term outcomes after curative gastrectomy for gastric cancer. PATIENTS AND
      METHODS: Overall, 1,281 consecutive gastric cancer patients, who underwent
      curative gastrectomy with radical lymphadenectomy from 1997 through 2012 were
      retrospectively analyzed. Low BMI and non-low BMI were defined as a BMI<18.5 and
      BMI>18.5 kg/m2, respectively. RESULTS: Compared to patients with BMI higher than
      18.5, those with BMI<18.5 had a significantly shorter duration of surgery
      (p<0.001) and tended to have lower blood loss (p=0.058). There was no difference
      in preoperative serum albumin level (p=0.592) and the incidence in postoperative
      abdominal infection complications (p=0.925) between the two groups. Whereas,
      BMI<18.5 was significantly associated with female gender, anemia, deeper tumor
      depth and nodal metastasis. Univariate and multivariate analyses revealed that
      the BMI<18.5 was an independent poor prognostic factor for overall survival
      [p=0.010, HR 1.6 (95%CI=1.32-2.30)]. Concerning recurrence, the cumulative
      incidence rate was significantly higher in patients with BMI<18.5 than those
      without (p=0.045). CONCLUSION: Low weight did not have adverse effects on short
      term outcomes including postoperative complications. However, there was a
      negative prognostic impact of low BMI, suggesting the requirement of meticulous
      treatments and follow-up in these gastric cancer patients.

PMID- 30194186
TI  - The Impact of Local Intervention Combined with Targeted Therapy on Metastatic
      Renal Cell Carcinoma.
AB  - BACKGROUND/AIM: We performed a retrospective survey on our metastatic renal cell
      carcinoma (MRCC) patients who had received targeted therapies, and afterwards
      evaluated the clinical impacts of local interventions on the patient outcomes.
      MATERIALS AND METHODS: Between 2006 and 2016, 124 patients with MRCC who had
      received at least one line of tyrosine kinase inhibitors or mammalian target of
      rapamycin were included in the study. Seventy-five patients (60.5%) received
      targeted therapies only, twenty-six patients received complete resection and the
      remaining 23 received incomplete local interventions for their metastatic
      lesions. Analysis of the basic characteristics, overall survival and multi
      variant regression amongst the three groups was performed. RESULTS: The age,
      gender distribution, tumor cell type, targeted therapy selection, line of
      therapies and sites of metastases were not different amongst the three groups.
      The targeted therapy-only group had a significantly higher percentage of Memorial
      Sloan Kettering Cancer Center (MSKCC) poor-risk patients compared with the other
      two groups (22.7% vs. 3.8% and 0%, p=0.006 respectively). The targeted treatment
      duration and follow-up duration was significantly shorted in the targeted therapy
      only group. Of the twelve variables analyzed, complete resection and MSKCC poor
      risk group showed a significant impact on the overall survival rate (HR=0.5,
      95%CI=0.25-0.98, p=0.045; HR=2.97, 95%CI=1.05-8.4, p=0.04 respectively).
      CONCLUSION: Complete resection of metastatic sites for MRCC patients, combined
      with targeted therapy, could provide better overall survival rates than targeted
      therapy alone. Poor MSKCC risk is still correlated to a poor outcome in the
      current targeted therapy era.

PMID- 30194187
TI  - Impact of Lymph Node Yield on Outcome of Patients with Head and Neck Cancer and
      pN0 Neck.
AB  - BACKGROUND/AIM: The extent of neck dissection in patients with head and neck
      cancer (HNSCC) and N0 neck remains controversial. The aim of this study was to
      evaluate the influence of lymph node yield on overall survival in patients with
      pathologically node-negative HNSCC. PATIENTS AND METHODS: A retrospective
      analysis was performed on 157 pN0 HNSCC patients undergoing primary surgery with
      neck dissection between 2000 and 2014. The patients were divided into three
      groups according to the lymph node count using the optimal cut-points method. The
      Kaplan-Meier method and log-rank test were used to analyze overall survival and
      compare survival curves. RESULTS: The lymph node count cut-offs were determined
      to be 15 and 40. A total of 22 patients had 1-14, 79 patients had 15-39 and 56
      patients had 40 or more harvested lymph nodes. There were significant differences
      in survival between all groups (p=0.001). CONCLUSION: A lymph node yield of at
      least 15 nodes was significantly associated with better overall survival in
      pathologically node-negative patients who underwent surgical resection of HNSCC.

PMID- 30194188
TI  - Serum Carcinoembryonic Antigen Levels Before the First Curative Hepatectomy for
      Metastatic Colorectal Cancer Is a Predictor of Recurrence.
AB  - BACKGROUND/AIM: The aim of this study was to evaluate the usefulness of serum
      carcinoembryonic antigen (CEA) levels before the first curative hepatectomy for
      metastatic colorectal cancer as a predictor of recurrence. PATIENTS AND METHODS:
      Between 2003 and 2010, 66 patients (45 male and 21 female) who underwent a first
      curative hepatectomy for metastatic colorectal cancer in our hospital were
      evaluated retrospectively. The mean patient age was 65.2 years (range=31-80
      years). A total of 28 patients had synchronous liver metastasis, and the other 38
      patients developed metachronous liver metastasis. RESULTS: The 5-year relapse
      free survival rate after the first hepatectomy of the 16 patients with normal
      serum CEA level was 61.1%, whereas that of the 50 patients with abnormal serum
      CEA level was 34.3% (p<0.001). Among patients whose serum CEA levels were
      abnormal, the 5-year relapse-free survival rate after the first hepatectomy of
      the 34 patients with serum CEA levels less than 50 ng/ml was 48.1%, whereas that
      of the 16 patients with serum CEA level equal to or greater than 50 ng/ml was
      6.3% (p<0.001). All eleven patients whose serum CEA levels were at least 100
      ng/ml developed recurrence within one year after hepatectomy. CONCLUSION: Serum
      CEA levels before the first curative hepatectomy for metastatic colorectal cancer
      seem to be a predictor of recurrence.

PMID- 30194189
TI  - Evaluation of the Prognostic Stage in the 8th Edition of the American Joint
      Committee on Cancer in Patients with Breast Cancer and Internal Mammary Lymph
      Node Metastasis.
AB  - BACKGROUND/AIM: This study evaluated the prognostic value of the 8th edition of
      American Joint Committee on Cancer (AJCC) cancer staging system for patients with
      internal mammary lymph node (IMN) metastases. MATERIALS AND METHODS: Of the
      patients with breast cancer who were treated between 2009 and 2013, 66 were
      diagnosed as cN3b. We restaged the patients and analyzed the prognostic value of
      the prognostically staged groups. RESULTS: With a median follow-up of 53.9
      months, the 5-year overall survival rates of patients with IIIA, IIIB, and IIIC
      stages were 100%, 95%, and 50% (p=0.001), while the progression-free survival
      rates were 100%, 83%, and 50% (p=0.005). CONCLUSION: Despite the small number of
      patients, the prognostic stage provided accurate information for IMN metastasized
      breast cancer, which will lead to more accurate prognosis predictions and optimal
      treatment selection.

PMID- 30194190
TI  - Complete Remission and Long-term Survival of a Patient with a Diffuse Large B
      cell Lymphoma Under Viscum album Extracts After Resistance to R-CHOP: A Case
      Report.
AB  - BACKGROUND: A nodular lymphocyte predominant Hodgkin's lymphoma (NLPHL) is a
      lymphoproliferative neoplasm with a fair prognosis, but the possibility of a
      malignant transformation into a diffuse large B-cell lymphoma (DLBCL) is high.
      DLBCL progresses aggressively. Introduction of rituximab into therapy had led to
      improved outcomes. The use of Viscum album extracts (VAE) in cancer is
      established, but their application in lymphoma are rare. CASE PRESENTATION: A 65
      year-old patient was diagnosed with DLBCL stage IIa with splenomegaly,
      transformed from a NLPHL, after a 30-year history of repeatedly enlarged inguinal
      lymph nodes. The patient initially rejected chemotherapy. After his tumor pain
      increased, he accepted the consecutive therapies bendamustine plus vincristine
      plus prednisolone, trofosfamide, and rituximab plus cyclophosphamide plus
      hydroxydaunorubicin plus vincristine plus prednisone (R-CHOP), inducing only a
      slight regression of the splenic lesions. VAE was additionally applied to R-CHOP.
      Five months after termination of chemotherapy - under continued VAE therapy in
      increasing dosage- regression of paraaortal lesions was found. The patient fully
      recovered under continuous VAE application and is in ongoing complete remission
      and in a good state of health 17 years after the initial diagnosis. CONCLUSION:
      As complete remission of lymphoproliferative disorders after VAE treatment has
      been previously reported, further investigations of VAE in lymphoma seem highly
      worthwhile.

PMID- 30194191
TI  - Role of Neoadjuvant Radio-chemotherapy for the Treatment of High Rectal Cancer.
AB  - BACKGROUND/AIM: Controversy exists regarding treatment of high rectal cancer. The
      role of neoadjuvant radio-chemotherapy was investigated. PATIENTS AND METHODS:
      Fifty-four patients receiving neoadjuvant radio-chemotherapy (50.4 Gy & 2 courses
      of concurrent chemotherapy) for stage II/III high rectal cancer (10.1-15.0 cm
      from anal verge) were retrospectively analyzed. Following microscopicallly
      complete resection of primary tumor and involved lymph nodes in all patients, <=6
      courses of chemotherapy were given. RESULTS: Five-year rates of local control
      (LC), metastases-free survival (MFS) and overall survival (OS) were 90%, 79% and
      77%. On multivariate analyses, LC was associated with lower pathological UICC
      stage at surgery (p=0.003) and successful downstaging (p=0.007), MFS with higher
      regression grade (p=0.014) and OS with lower Union for International Cancer
      Control (UICC)-stage (p=0.017) and downstaging (p=0.034). Grade 3 acute
      toxicities occurred in 19% of patients; grade >=3 late toxicities were not
      observed. Manageable surgery-related complications occurred in 43%. CONCLUSION:
      Neoadjuvant radio-chemotherapy for high rectal cancer was well tolerated and led
      to promising results. Comparative studies are required to investigate whether it
      is superior to postoperative chemotherapy alone.

PMID- 30194192
TI  - Clinicopathological Stratification and Long-term Follow-up of Patients with
      Periampullary Carcinomas.
AB  - BACKGROUND: Periampullary carcinomas generally confer a poor outcome. Choosing
      the most effective treatment regimen for each sub-entity proves challenging and
      is usually based on experience from pancreatic adenocarcinoma (PDAC). PATIENTS
      AND METHODS: The long-term follow-up is presented of 472 patients with
      periampullary tumors [PDAC, distal cholangiocarcinoma (dCC) and ampullary
      carcinomas (AC)] who underwent radical resection considering clinical
      characteristics, paraclinical findings and histopathological features in order to
      define factors of prognostic relevance. RESULTS: Patients with PDACs presented
      with larger tumor sizes, more frequent R1 resection, higher rate of nodal and
      perineural invasion, higher tumor stage according to the classification of tumors
      of the Union Internationale contre le Cancer when compared to those with dCCs and
      ACs. In a multivariate analysis, age >65 years, postoperative complications and
      higher grading of the tumor proved to be independent prognostic factors for
      survival. CONCLUSION: Patients suffering from PDAC have the worst prognosis and
      greatest benefit from radical resection of all patients with periampullary
      tumors. More detailed studies are warranted to better distinguish between the
      different entities.

PMID- 30194193
TI  - Efficacy of Axitinib as Second-line Treatment in Locally Advanced and Metastatic
      Renal Cell Carcinoma.
AB  - AIM: To investigate prognostic factors for patients with advanced renal cell
      carcinoma (RCC) treated with axitinib as second-line therapy. PATIENTS AND
      METHODS: This study included 35 patients with RCC who received axitinib as second
      line therapy after the failure of first-line tyrosine kinases inhibitor from
      November 2012 to March 2017. RESULTS: In univariate analyses, the following
      factors were associated with poor prognosis: bone and extrapulmonary metastasis
      for progression-free survival; and prior nephrectomy, Memorial Sloan Kettering
      Cancer Center risk classification, International Metastatic Renal Cell Carcinoma
      Database Consortium (IMDC) risk classification of poor, extrapulmonary metastasis
      and early tumor response for overall survival. Multivariate analyses identified
      the following factors as independent poor prognostic effects: extrapulmonary
      metastasis for progression-free survival, and no prior nephrectomy, IMDC risk
      classification of poor and extrapulmonary metastasis for overall survival.
      CONCLUSION: Axitinib as second-line treatment is effective for patients with
      pulmonary metastasis alone of RCC, but not for those with extrapulmonary
      metastasis.

PMID- 30194194
TI  - Predicting Response to Standard First-line Treatment in High-grade Serous Ovarian
      Carcinoma by Angiogenesis-related Genes.
AB  - BACKGROUND/AIM: Predicting response to treatment in high-grade serous ovarian
      carcinoma (HGSOC) still remains a clinical challenge. The standard-of-care for
      first-line chemotherapy, based on a combination of carboplatin and paclitaxel,
      achieves a high response rate. However, the development of drug resistance is one
      of the major limitations to efficacy. Therefore, identification of biomarkers
      able to predict response to chemotherapy in patients with HGSOC is a critical
      step for prognosis and treatment of the disease. Several studies suggest that
      angiogenesis is an important process in the development of ovarian carcinoma and
      chemoresistance. The aim of this study was to identify a profile of angiogenesis
      related genes as a biomarker for response to first-line chemotherapy in HGSOC.
      MATERIALS AND METHODS: Formalin-fixed paraffin-embedded samples from 39 patients
      with HGSOC who underwent surgical cytoreduction and received a first-line
      chemotherapy with carboplatin and paclitaxel were included in this study.
      Expression levels of 82 angiogenesis-related genes were measured by quantitative
      real-time polymerase chain reaction using TaqMan low-density arrays. RESULTS:
      Univariate analysis identified five genes [angiopoietin 1 (ANGPT1), aryl
      hydrocarbon receptor nuclear translocator (ARNT), CD34, epidermal growth factor
      (EGF) and matrix metallopeptidase 3 (MMP3)] as being statistically associated
      with response to treatment. Multivariable analysis by Lasso-penalized Cox
      regression generated a model with the combined expression of seven genes
      [angiotensinogen (AGT), CD34, EGF, erythropoietin receptor (EPOR), interleukin 8
      (IL8), MMP3 and MMP7)]. The area under the receiver operating characteristics
      curve (0.679) and cross-validated Kaplan-Meier survival curves were used to
      estimate the accuracy of these predictors. CONCLUSION: An angiogenesis-related
      gene expression profile useful for response prediction in HGSOC was identified,
      supporting the important role of angiogenesis in HGSOC.

PMID- 30194195
TI  - Image-guided Interstitial Brachytherapy in the Management of Metastasized Anal
      Squamous Cell Carcinoma.
AB  - BACKGROUND/AIM: Interstitial brachytherapy (IBT) has been shown to provide high
      tumor control rates in metastatic colorectal carcinoma. Our aim was to evaluate
      efficacy and safety of IBT in patients with metastatic anal squamous cell
      carcinoma (mASCC). PATIENTS AND METHODS: Seven patients with a total of 38
      unresectable ASCC metastases (28 liver, nine lung, one nodal metastases) were
      treated with computed tomographic or open magnetic resonance imaging-guided IBT
      using an iridium-192 source. Clinical and image-based follow-up were performed
      every 3 months after treatment. RESULTS: Local tumor control rate was 97.4%
      during a median follow-up of 15.2 months. Median progression-free survival was
      3.3 months (range=2.5-32.6 months). Median overall survival after IBT was 25.2
      months (range=6.5-51.0 months). No severe adverse events (grade 3 or more) were
      recorded. CONCLUSION: Image-guided IBT is a safe and particularly effective
      treatment in patients with mASCC and might provide a well-tolerated therapeutic
      option in a multidisciplinary setting.

PMID- 30194196
TI  - Real Clinical Practice of Using Afatinib Therapy in NSCLC Patients with an
      Acquired EGFR T790M Mutation.
AB  - BACKGROUND/AIM: To describe real clinical outcomes when using afatinib therapy to
      treat non-small cell lung cancer patients who have an acquired EGFR T790M
      mutation. MATERIALS AND METHODS: A retrospective chart review was conducted from
      January 2013 to November 2017 sourced from 15 medical institutes that cover a
      population of three million people. RESULTS: There were 74 patients who met the
      above-mentioned criteria. Treatment outcomes with afatinib, in patients with or
      without tyrosine kinase inhibitor (TKI) therapy prior to afatinib, were similar
      to previously reported clinical trials. Stratification of patients by the
      presence or absence of TKI pretreatment before afatinib, and the presence or
      absence of an acquired T790M mutation found no statistical difference in overall
      survival. CONCLUSION: This population-based study found that the disadvantages of
      pretreatment before afatinib, and absence of an acquired T790M EGFR mutation,
      could be overcome by an appropriate treatment strategy in clinical practice.

PMID- 30194197
TI  - Cholecystectomy Patients with High Plasma Level of Catalase Have Significantly
      Lower Analgesia Requirement: A Prospective Study of Two Different Cholecystectomy
      Techniques with Special Reference to Patients with Cancer.
AB  - BACKGROUND/AIM: The plasma level of the oxidative stress biomarker catalase in
      patients with gallstone disease has not been previously compared with that of
      patients with cancer. Moreover, the number of analgesic doses required during the
      first 24 h postoperatively (NAD24) after laparoscopic cholecystectomy (LC) or
      mini-cholecystectomy (MC) in patients with gallstones is unreported. The aim of
      the present study was to determine the correlation between the plasma catalase
      level in patients with gallstones according to cholecystectomy technique versus
      patients with cancer. PATIENTS AND METHODS: Initially, 114 patients with
      symptomatic gallstone disease were randomized into LC (n=54) or MC (n=60) groups.
      The plasma level of catalase was measured immediately before, immediately after
      and 6 hours after operation. RESULTS: The median plasma catalase levels
      preoperatively and following surgery in the LC and MC patients versus those with
      cancer did not differ statistically significantly. The median plasma level of
      catalase increased immediately after operation, but the alteration was
      statistically insignificant (p=0.132). Interestingly, there was a statistically
      significant weak inverse correlation between the individual NAD24 and median
      plasma catalase values postoperatively in patients with gallstone disease (r=
      0.283, p=0.042). CONCLUSION: The plasma catalase levels preoperatively and
      following surgery in the LC and MC patients versus those with cancer were quite
      similar. Cholecystectomy patients with high plasma levels of catalase appeared to
      require significantly fewer analgesic doses during the first 24 hours
      postoperatively (NAD24), suggesting that better oxidative balance following
      surgery could have a protective role against postoperative pain.

PMID- 30194198
TI  - Single-centre Experience of Use of Radium 223 with Clinical Outcomes Based on
      Number of Cycles and Bone Marrow Toxicity.
AB  - BACKGROUND: Bone is the most common site of metastatic disease in advanced
      prostate cancer. Radium-223 (223Ra) is a calcium-mimetic alpha-particle emitter,
      which has been shown to have activity in prostate cancer with clinical benefit in
      patients with symptomatic bone metastasis. The recommended schedule is six cycles
      of 223Ra, 5 kBq/kg, at 4-weekly intervals. Although previous studies have
      assessed clinical outcomes in patients who received six cycles of Ra223, there is
      very little information about outcomes of patients receiving fewer courses of
      treatment. PATIENTS AND METHODS: Patients with hormone-refractory metastatic
      prostate cancer treated from May 2014 to August 2016 were included in this
      retrospective study. A total of 113 patients were identified with a median age of
      76 (range=52-92) years. The median number of cycles administered was 5 (range=1
      6) with 54 (48%) completing six cycles of treatment. Eighty-five patients (75%)
      received 223Ra prior to docetaxel chemotherapy and 28 (25%) received it after
      receiving docetaxel. RESULTS: Eleven patients developed grade 2/3
      thrombocytopenia, and none of these received further 223Ra. Only 25% of patients
      who had a haemoglobin level of 10 g/dl or below at the start of the treatment
      were able to complete six courses of 223Ra. Of the patients who completed fewer
      than six cycles of 223Ra (1-5 cycles), the survival was 121 days, compared to 398
      days in men who received six cycles (odds ratio(OR)=4.767, 95% confidence
      internal(CI)=1.07-21.25; p=0.0005). CONCLUSION: Careful selection of patients is
      essential to obtain good clinical outcomes from 223Ra therapy. When fewer than
      six cycles were delivered then a beneficial survival effect was not seen.

PMID- 30194199
TI  - Outcome of Patients with Metastatic Castration-resistant Prostate Cancer After
      PSA Progression with Abiraterone Acetate.
AB  - BACKGROUND/AIM: The main purpose of this study was to evaluate the outcome of
      patients with prostate-specific antigen (PSA) progression after abiraterone
      acetate (AA) treatment for metastatic castration-resistant prostate cancer
      (mCRPC). PATIENTS AND METHODS: Between 2012 and 2017, 83 patients with clinically
      confirmed mCRPC previously treated with docetaxel with/without cabazitaxel
      followed by AA were included in this retrospective study. All patients received
      1,000 mg AA with 5 or 10 mg prednisolone. Among them, 59 were eligible for this
      study based on PSA progression during the clinical course. Patients were divided
      into two groups, AA responders and AA non-responders according to previous PSA
      response to AA treatment. Overall survival and treatment response to subsequent
      therapy were analyzed. RESULTS: The median overall survival of the 59 patients
      after AA-treated PSA progression was 12 (95% confidence interval(CI)=7.6-16.4)
      months and was longer in the AA-responding group compared to the non-responding
      group (25 vs. 8 months, p<0.001). The survival time after PSA progression on AA
      was longer in the AA-responsive group despite not being statistically different
      (13 vs. 7 months, p=0.126). Patients with AA treatment who received subsequent
      therapies after PSA progression had better overall survival than those without
      (18 vs. 4 months, p=0.003). In addition, there was a trend for better
      chemotherapy response in AA non-responders than AA responders, 62.5% (5/8) vs.
      12.5% (1/8) respectively. CONCLUSION: In our small retrospective patient
      experience, effective sequential treatments for patients with mCRPC provided
      overall survival benefit. Previous treatment response can act as a clinical
      predictor for subsequent treatment.

PMID- 30194200
TI  - Prediction of Response to Stereotactic Radiosurgery for Brain Metastases Using
      Convolutional Neural Networks.
AB  - BACKGROUND: It is unclear whether radiomic phenotypes of brain metastases (BM)
      are related to radiation therapy prognosis. This study assessed whether a
      convolutional neural network (CNN)-based radiomics model which learned computer
      tomography (CT) image features with minimal preprocessing, could predict early
      response of BM to radiosurgery. MATERIALS AND METHODS: Tumor images of 110 BM
      post stereotactic-radiosurgery (SRS) (within 3 months) were assessed (Response
      Evaluation Criteria in Solid Tumor, version 1.1) as responders (complete or
      partial response) or non-responders (stable or progressive disease). Datasets
      were axial planning CT images containing the tumor center, and the tumor
      response. Datasets were randomly assigned to training, validation, or evaluation
      groups repeatedly, to create 50 dataset combinations that were classified into
      five groups of 10 different dataset combinations with the same evaluation
      datasets. The CNN learned using training-group images and labels. Validation
      datasets were used to choose the model that best classified evaluation images as
      responders or non-responders. RESULTS: Of 110 tumors, 57 were classified as
      responders, and 53 as non-responders. The area under the receiver operating
      characteristic curve (AUC) of each CNN model for 50 dataset combinations ranged
      from 0.602 [95% confidence interval (CI)=36.5-83.9%] to 0.826 [95% CI, 64.3
      100%]. The AUC of ensemble models, which averaged prediction results of 10
      individual models within the same group, ranged from 0.761 (95% CI=55.2-97.1%) to
      0.856 (95% CI=68.2-100%). CONCLUSION: A CNN-based ensemble radiomics model
      accurately predicted SRS responses of unlearned BM images. Thus, CNN models are
      able to predict SRS prognoses from small datasets.

PMID- 30194201
TI  - Primary Tumor Score Based on Tumor Depth and Length Predicts Prognosis in
      Esophageal Squamous Cell Carcinoma.
AB  - AIM: To examine the depth of tumor invasion and tumor length and assess the
      clinical impact of the primary tumor score (PTS), based on a combination of tumor
      invasion and tumor length, in patients with esophageal squamous cell carcinoma
      (ESCC). PATIENTS AND METHODS: A total of 237 patients with ESCC were classified
      into three PTS groups based on cut-off values for deeper tumor invasion (pT2-T4)
      and greater tumor length (>=44 mm). A PTS of 2 indicated the presence of both of
      these abnormalities, 1 indicated one of these abnormalities, and 0 indicated
      neither abnormality. RESULTS: PTS was significantly positively correlated with
      depth of tumor invasion, lymph node metastasis, lymphovascular invasion, and
      stage (all p<0.001). The prognosis differed significantly among the three groups
      based on PTS (p<0.0001). Multivariate analysis demonstrated that PTS was an
      independent prognostic factor (p=0.0004). CONCLUSION: PTS has a clinical utility
      as a prognostic predictor in patients with ESCC.

PMID- 30194202
TI  - Demographical Profile and Spectrum of Multiple Malignancies in Children and
      Adults with Neurocutaneous Disorders.
AB  - BACKGROUND/AIM: Neurocutaneous disorders, also referred as phacomatoses, are
      congenital disorders manifesting at different ages with central nervous system
      and cutaneous abnormalities. Analysis of the demographic and clinical profile of
      patients with phacomatoses in the context of the incidence and spectrum of
      malignancy. MATERIALS AND METHODS: This is a retrospective analysis of 20 years
      of data in a single-center study in Poland. RESULTS: Phacomatoses were diagnosed
      in 45.6% (913/2,003) of referred patients, including 61.4% children. The
      distribution of phacomatoses included: neurofibromatosis type 1 (NF1) in 92.4%,
      tuberous sclerosis complex (TSC) 3.9%, neurofibromatosis type 2 (NF2) 2.0%,
      Klippel-Trenaunay syndrome 0.5%, Von Hippel-Lindau syndrome 0.5%, and other
      sporadic diseases 0.7%. Non-phacomatosis patients were diagnosed mainly for cafe
      au-lait-macules (42.8%). The frequency of malignancy was 9.4% (86/913), including
      9.1% in patients with NF1; 27.8% in NF2; and 8.3% in TSC. Multiple malignancies
      were diagnosed in 0.7% and 7% of all phacomatosis and malignancy-diagnosed
      patients, respectively. CONCLUSION: The risk of malignancy in patients with
      phacomatoses was 21.3-fold higher than in the general population. The risk of
      secondary malignancy was 7%.

PMID- 30194203
TI  - Dynamic Contrast-enhanced Magnetic Resonance Imaging for Patients with Breast
      Cancer Receiving First-line Bevacizumab and Paclitaxel.
AB  - BACKGROUND: Bevacizumab plus paclitaxel shows promise for metastatic disease;
      however, there is no predictive biomarker. Dynamic contrast-enhanced (DCE)
      magnetic resonance imaging (MRI) is widely used to evaluate the efficacy of anti
      angiogenic therapies. PATIENTS AND METHODS: Patients with locally
      advanced/metastatic breast cancer who had not received any prior chemotherapy or
      hormone therapy were included. DCE-MRI was conducted at baseline and after one
      and two cycles of bevacizumab and paclitaxel. The percentage change in the volume
      transfer constant (DeltaKtrans) and the correlation of DeltaKtrans with tumour
      regression and time to progression (TTP) were evaluated. RESULTS: The mean
      DeltaKtrans from baseline after one and two cycles was -51.4% and -55.1%,
      respectively. Patients with DeltaKtrans >=50% displayed more tumour regression
      than those with DeltaKtrans <50%; TTP was not significantly different.
      CONCLUSION: We demonstrate a decrease in blood permeability following bevacizumab
      and paclitaxel using DCE-MRI and a correlation between DeltaKtrans and tumour
      regression.

PMID- 30194204
TI  - Clinicopathological Characteristics of Ovarian Metastasis from Colorectal and
      Pancreatobiliary Carcinomas Mimicking Primary Ovarian Mucinous Tumor.
AB  - BACKGROUND/AIM: A subset of carcinomas metastatic to the ovary can exhibit growth
      patterns closely resembling ovarian mucinous cystadenoma and borderline tumor.
      They can be misinterpreted as underlying primary ovarian mucinous tumors and can
      be erroneously used to suggest that the carcinomatous component arises from
      mucinous precursor lesions. MATERIALS AND METHODS: We investigated the
      clinicopathological characteristics of 11 cases of metastatic carcinoma that had
      metastasized from colorectal and pancreatobiliary carcinoma and mimicked primary
      ovarian mucinous tumors. RESULTS: The patient age ranged from 37 to 81 years old.
      Seven patients presented to gynecologists with non-specific pelvic symptoms
      similar to those of primary ovarian tumors. The primary tumor was identified
      before the detection of the ovarian lesion in 6 cases, synchronously in 5, and
      postoperatively in 1 case. The ovarian tumors were bilateral in 6 cases. The
      greatest dimension of the metastatic tumors ranged from 4.8 to 23.0 cm.
      Multinodularity was present in 7 cases, and surface involvement was identified in
      5 cases. An infiltrative growth pattern was present, at least focally, in 8
      cases. Six and 2 cases exhibited cystadenomatous and borderline-like growth
      patterns, respectively. CONCLUSION: Although the diagnosis of metastatic tumors
      to the ovary is possible in most cases on the basis of clinical presentation and
      standard diagnostic criteria, their differential diagnosis may be problematic
      because of morphological patterns that strikingly overlap with those of primary
      ovarian benign, borderline, and malignant mucinous tumors. The possibility of
      metastases should be considered when evaluating ovarian mucinous tumors.

PMID- 30194205
TI  - Tumor Size-driven Dose of Intraoperative Radiotherapy for Breast Cancer: 18 Gy
      Versus 21 Gy.
AB  - AIM: To test whether a reduced total single dose of 18 Gy of intraoperative
      radiotherapy with electrons (IORT) may be tailored to safely treat patients in
      comparison with the standard dose of 21 Gy. (NCT01276938). PATIENTS AND METHODS:
      From October 2009 to December 2011, 199 females affected by breast cancer were
      treated with conservative surgery and IORT with two different exclusive doses, 18
      or 21 Gy. RESULTS: The median follow-up was 91 months (16-104 months). Sixty-five
      patients (pT1a?b, pN0?mic, pMx, G1-G3) received 18 Gy and 134 patients (pT1c?2,
      pN0?mic, pMx, G1-G3) received 21 Gy. No significant difference in local
      recurrence-free survival or overall survival was detected in the 18 Gy-treated
      arm versus that treated with 21 Gy: 96.9% vs. 96.3%, p=0.72, and 96.9% vs. 95.5%,
      p=0.82, respectively at 5 years. CONCLUSION: The lower dose of 18 Gy achieved
      excellent results in terms of local toxicity and local control in early breast
      cancer.

PMID- 30194206
TI  - Recurrence Rates and Characteristics of Phyllodes Tumors Diagnosed by Ultrasound
      guided Vacuum-assisted Breast Biopsy (VABB).
AB  - BACKGROUND/AIM: Recently, the development of ultrasonography (US)-guided vacuum
      assisted breast biopsy (VABB) has enabled the excision of benign breast tumors
      with normal surrounding breast tissues; thus, complete excision is possible
      without residual tumor tissue. We sought to identify the clinicopathological
      characteristics and recurrence rates of benign phyllodes tumors diagnosed by US
      guided VABB. PATIENTS AND METHODS: Data from 11,221 US-guided VABBs performed at
      the Gangnam Cha Medical Center over 12 years were analyzed. Eighty-three lesions
      were diagnosed as benign phyllodes tumors; 67 with >24 months of follow-up data
      were investigated. All lesions were excised using an 8-gauge probe without
      residual tissue; patients underwent follow-up US every 3-6 months. RESULTS: Five
      patients (7.46%) experienced local recurrence during a mean follow-up period of
      27.8 months; no distant metastases occurred. The mean tumor size was 3.0 cm in
      the recurrence group and 1.87 cm in the non-recurrence group (p=0.05).
      CONCLUSION: Benign phyllodes tumors excised and diagnosed using VABB showed a low
      recurrence rate during the follow-up period; thus, these tumors, particularly
      those <3 cm, can be safely monitored with ultrasonography instead of performing
      immediate re-excision.

PMID- 30194207
TI  - TTF-1 Expression Predicts the Merit of Additional Antiangiogenic Treatment in Non
      squamous Non-small Cell Lung Cancer.
AB  - BACKGROUND/AIM: To investigate whether TTF-1 expression predicts a beneficial
      response of non-squamous non-small-cell lung cancer (NS-NSCLC) patients to
      bevacizumab. PATIENTS AND METHODS: We retrospectively screened 118 advanced NS
      NSCLC patients who were treated with pemetrexed plus platinum derivatives alone
      (Bev(-)) or with bevacizumab (Bev(+)), and investigated the relationship between
      expression of TTF-1 and treatment outcomes. RESULTS: Among the 92 TTF-1-positive
      patients, clinical outcomes in the Bev(+) group were significantly better than
      those in the Bev(-) group (response rate, 51.4% vs. 27.3%, p=0.027; median
      progression-free survival, 216 days vs. 137 days, p=0.012). Overall survival in
      the Bev(+) group tended to be longer than that in the Bev(-) group. However, the
      addition of bevacizumab to the standard treatment of 26 TTF-1-negative patients
      offered no clinical benefit. CONCLUSION: TTF-1 expression may serve as a
      predictive marker to identify patients who may benefit from the addition of
      bevacizumab to platinum doublet therapy.

PMID- 30194208
TI  - The Combination of Neutrophil-to-lymphocyte Ratio and Serum Carbohydrate Antigen
      19-9 Level as a Prognostic Indicator in Patients with Recurrent Pancreatic
      Cancer.
AB  - BACKGROUND/AIM: We retrospectively investigated the relationship between
      prognosis and combined neutrophil-to-lymphocyte ratio (NLR) and serum
      carbohydrate antigen 19-9 (CA19-9) levels in patients with recurrent pancreatic
      cancer. PATIENTS AND METHODS: We enrolled 66 patients whose pancreatic cancer
      recurred. RESULTS: Based on ROC analysis results, the patients were divided into
      NLRHigh (NLR >=1.69) or NLRLow (NLR <1.69), and into CA19-9High (CA19-9 >=107.95
      U/ml) or CA19-9Low (CA19-9 <107.95 U/ml). When the patients were grouped by
      combined NLR and CA19-9, their 2-year survival rates were NLRLow/CA19-9Low:
      58.7%; NLRLow/CA19-9High or NLRHigh/CA19-9Low (grouped together): 11.2%; and
      NLRHigh/CA19-9High: 0% (p<0.0001). Finally, in multivariate analysis, the
      combination of NLR and serum CA19-9 level was an independent prognostic factor in
      patients with recurrent pancreatic cancer. CONCLUSION: The combination of NLR and
      serum CA19-9 level is a useful prognostic indicator for recurrent pancreatic
      cancer.

PMID- 30194209
TI  - The Radiological Differentiation of Hypervascular Intrahepatic Cholangiocarcinoma
      from Hepatocellular Carcinoma with a Focus on the CT Value on Multi-phase
      Enhanced CT.
AB  - BACKGROUND/AIM: This study aimed to investigate whether hypervascular
      intrahepatic cholangiocarcinoma (HICC) can be differentiated from hepatocellular
      carcinoma (HCC). MATERIALS AND METHODS: Among 100 patients with intrahepatic
      cholangiocarcinoma, 22 patients were diagnosed with HICC based on the computed
      tomography (CT) value in the late arterial phase as follows: the CT value of the
      tumor >= that of the liver parenchyma. The CT values of the HICC were compared to
      those of HCC cases (n=120). RESULTS: The CT value of HICC was lower in the
      unenhanced phase (UP) (p=0.016) and higher in the equilibrium phase (EP)
      (p<0.001) in comparison to HCC. The non-tumorous liver (odds ratio [OR]: 6.35,
      p=0.002) and an E/U ratio (the mean CT value of the tumor in the EP to that in
      the UP) of >2.3 (OR=13.1, p<0.001) were independent diagnostic factors for
      differentiating HICC from HCC. CONCLUSION: E/U ratio is useful for
      differentiating between HICC and HCC.

PMID- 30194210
TI  - Serum Asunaprevir and Daclatasvir Concentrations and Outcomes in Patients with
      Recurrent Hepatitis C Who Have Undergone Living Donor Liver Transplantation.
AB  - BACKGROUND/AIM: This study's aim was to investigate the safety and effectiveness
      of asunaprevir and daclatasvir treatment for recurrent hepatitis C virus (HCV)
      infection in transplant recipients. The study cohort comprised 14 transplant
      recipients with recurrent hepatitis C who were receiving asunaprevir and
      daclatasvir. PATIENTS AND METHODS: Serum concentrations of asunaprevir and
      daclatasvir, their therapeutic effects, trough concentrations/dose ratios of
      tacrolimus, and adverse effects were evaluated. RESULTS: Hepatitis C virus was
      still undetectable in 12 (85.7%) out of 14 patients 12 weeks after completing
      treatment. One week after starting treatment, asunaprevir concentrations were
      significantly higher in patients with baseline albumin concentrations <=3.6 g/dl
      than in those with baseline albumin concentrations >3.6 g/dl. No marked
      fluctuations were identified in tacrolimus trough concentrations/dose ratios
      during the 24 weeks of therapy. CONCLUSION: Full doses of asunaprevir and
      daclatasvir-based treatment can be safely and effectively administered to liver
      transplant recipients for recurrent HCV genotype 1b after living donor liver
      transplantation (LDLT) with little effect on blood concentrations of tacrolimus.

PMID- 30194211
TI  - Iterative Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for
      Recurrent Peritoneal Metastases.
AB  - BACKGROUND: Our aim was to analyze the safety and efficacy of iterative
      cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (iCRS-HIPEC)
      in patients with peritoneal recurrence from different tumor types. PATIENTS AND
      METHODS: Data on indications, intraoperative findings and postoperative outcome
      of all patients treated with iCRS-HIPEC at our Institution were reviewed.
      RESULTS: Between 2010-2018, 10 iCRS-HIPEC procedures for peritoneal recurrence in
      eight patients were performed. The median peritoneal cancer index was 14.5
      (range=2-33). Completeness of cytoreduction was CC0-1 in most cases (9/10). Three
      grade III-IV complications (two intestinal fistulas, one bleeding) were recorded
      and there was no operative mortality. After a median follow-up of 19.5 months,
      six patients experienced recurrence after a median of 12.5 months. CONCLUSION:
      iCRS-HIPEC is a safe procedure in selected patients with recurrent peritoneal
      surface malignancies. Selection criteria still remain questionable and need to be
      further evaluated in large cooperative multi-institution studies.

PMID- 30194212
TI  - A Combination of Findings Obtained from Pre- and Postoperative Imaging Predict
      Recovery of Urinary Continence After Non-nerve-sparing Laparoscopic Radical
      Prostatectomy.
AB  - BACKGROUND/AIM: The aim of the study was to identify the reliable predictor for
      early recovery of urinary continence (UC) after non-nerve-sparing laparoscopic
      radical prostatectomy (NNS-LRP) according to the findings of pre- and
      postoperative imaging. MATERIALS AND METHODS: A retrospective analysis of 215
      patients who underwent NNS-LRP was carried out. Early recovery of UC was defined
      as using no pads or one security pad per day within 3 months. Preoperative
      membranous urethral length (MUL) measured on MRI and postoperative bladder neck
      angle (BNA) identified by cystography were analyzed to evaluate the relationship
      with recovery of UC. Patients were divided into three groups based on MUL and BNA
      (Group A: MUL >=12.1 mm and BNA >=103 degrees , Group B: either MUL >=12.1 mm or
      BNA >=103 degrees , Group C: MUL <12.1 mm and BNA <103 degrees . RESULTS: Early
      recovery rates were 80.3% in patients with MUL >=12.1 mm, 37.5% in patients with
      MLU<12.1 (p<0.001), and 77.8% in patients with BNA >=103 degrees , 50% in
      patients with BNA <103 degrees (p<0.001). In the combination of the two
      parameters, early recovery rates were 90.4%, 58%, and 36.1% in group A, B and C
      respectively (p<0.001). Kaplan-Meier curve of the time to recovery of UC showed
      significant differences among the three groups (log rank test: p<0.001).
      CONCLUSION: A combination of preoperative MUL and postoperative BNA was the
      reliable predictor of recovery of UC after NNS-LRP. Longer MUL with wider BNA is
      significantly and positively associated with an early recovery of UC.

PMID- 30194213
TI  - Portal Vein Embolization (PVE) Versus PVE with Haematopoietic Stem Cell
      Application in Patients with Primarily Non-resectable Colorectal Liver
      Metastases.
AB  - BACKGROUND: Portal vein embolization (PVE) and PVE with autologous mesenchymal
      stem cell application (PVE-MSC) increases future liver remnant volume (FLRV). The
      aim of this study was to compare both methods from the aspect of FLRV growth,
      progression of colorectal liver metastases (CLM), CLM resectability and long-term
      results. PATIENTS AND METHODS: Fifty-five patients with CLM and insufficient FLRV
      were included in the study. FLVR growth and CLM volume were evaluated using
      computed tomography. Liver resection was performed in patients with FLVR >30% of
      total liver volume. RESULTS: In the PVE (N=27) group, FLRV growth was observed in
      23 patients (85.2%) and in 100% of patients in the PVE-MSC (N=28) group (p<0.05).
      The rapidity of FLRV and CLM growth did not differ between groups. R0 resection
      was performed in 14 (51.8%) and 24 (85.7%) patients from the PVE and PVE-MSC
      (p<0.02) groups, respectively. The 3-year overall and progression-free survival
      rates were 85.75% and 9.3% in the PVE group and 68.7% and 17.1% in the PVE-MSC
      group, respectively (p<0.67 and p<0.84, respectively). CONCLUSION: PVE-MSC allows
      for more effective growth of FLRV and resectability of CLM compared to PVE. The
      two methods do not differ in their long-term results.

PMID- 30194214
TI  - Impact of Primary Tumor Localization on the Efficacy of Bevacizumab in Metastatic
      Colorectal Cancer.
AB  - AIM: Right- and left-sided primary tumors of colorectal origin differ
      substantially in several aspects. Recent retrospective analyses show distinct
      efficacy of EGFR-epidermal growth factor receptor (EGFR)-directed therapies for
      left- and right-sided primary tumors. Current treatment guidelines have
      accommodated these findings such that for right-sided primary tumors, EGFR
      directed therapy is no longer recommended. Instead, vascular endothelial growth
      factor (VEGF)-directed therapies are recommended frequently in first line, even
      in tumors with wild-type rat sarcoma (RAS) status. However, data supporting this
      recommendation are scarce. The purpose of this analysis was to investigate the
      efficacy of bevacizumab added to chemotherapy depending on the primary tumor
      localization in a retrospective setting. PATIENTS AND METHODS: From the central
      clinical cancer registry of one of Germany's largest medical centers, data were
      analyzed for patients with metastatic colorectal cancer (mCRC) treated with
      either chemotherapy alone (CT) or bevacizumab-containing regimens (BEV/CT).
      RESULTS: Of 1,080 documented mCRC cases within the period of 2003 through 2016,
      242 were treated with chemotherapy alone and 166 with bevacizumab-containing
      regimes in any line of therapy meeting the criterion above. In patients with left
      sided primary tumor localization, a significant survival benefit was found when
      bevacizumab was added to chemotherapy. Patients with right-sided primaries,
      instead, did not derive any advantage when bevacizumab was added to chemotherapy.
      For the whole group of patients, this translated into a trend towards improved
      survival in bevacizumab-treated patients with mCRC. CONCLUSION: Adding
      bevacizumab to chemotherapy in mCRC may be beneficial only in patients with left
      sided primary tumor, while those with right-sided primary tumors may have no
      additional benefit from the addition of bevacizumab. This hypothesis-generating
      analysis should provide a basis for in-depth analysis of this issue in future
      prospective trials.

PMID- 30194215
TI  - Synchronous Laryngeal Squamous Cell Carcinoma and Intrahepatic Cholangiocarcinoma
      Present in an Obese Male with Poor Prognosis.
AB  - Concurrent laryngeal squamous cell carcinoma and intrahepatic cholangiocarcinoma
      is rare and no prior report has been found through a PubMed search. Here we
      report such a case of a 51-year old obese male presenting with hoarseness and
      trouble swallowing for 2 to 3 months. Imaging findings of computer tomography
      (CT) and magnetic resonance imaging (MRI) with and without contrast were
      suspicious for a T3N2 supraglottic laryngeal cancer. Laryngeal biopsy showed a
      well differentiated squamous cell carcinoma (SCC). As part of the evaluation of
      the laryngeal SCC, MRI abdomen showed an enhancing mass (4.6 cm in the greatest
      dimension) with diffusion restriction and capsular retraction in the right lobe
      of the liver. Ultrasound-guided percutaneous biopsy of the liver revealed a
      moderately differentiated adenocarcinoma, that was strongly and diffusely
      positive for CK7 and CK19, weakly positive for CDX2, and negative for HepPar 1,
      glypican 3, CK20, PSA and TTF1. The immunohistochemistry profile was consistent
      with cholangiocarcinoma. This is a unique case of laryngeal squamous cell
      carcinoma with concurrent cholangiocarcinoma. The prognosis was poor and the
      patient was placed in hospice care in two months after the diagnoses. To the best
      of our knowledge, this is the first documented case of synchronous laryngeal
      squamous cell carcinoma and intrahepatic cholangiocarcinoma. The pathogenesis,
      diagnosis and treatment of the diseases are discussed.

PMID- 30194220
TI  - Age-dependent changes in GI physiology and microbiota: time to reconsider?
AB  - Our life expectancy is increasing, leading to a rise in the ageing population.
      Ageing is associated with a decline in physiological function and adaptive
      capacity. Altered GI physiology can affect the amount and types of nutrients
      digested and absorbed as well as impact the intestinal microbiota. The intestinal
      microbiota is considered a key player in our health, and a variety of studies
      have reported that microbiota composition is changing during ageing. Since ageing
      is associated with a decline in GI function and adaptive capacity, it is crucial
      to obtain insights into this decline and how this is related to the intestinal
      microbiota in the elderly. Hence, in this review we focus on age-related changes
      in GI physiology and function, changes of the intestinal microbiota with ageing
      and frailty, how these are associated and how intestinal microbiota-targeted
      interventions may counteract these changes.

PMID- 30194221
TI  - How well do activity monitors estimate energy expenditure? A systematic review
      and meta-analysis of the validity of current technologies.
AB  - OBJECTIVE: To determine the accuracy of wrist and arm-worn activity monitors'
      estimates of energy expenditure (EE). DATA SOURCES: SportDISCUS (EBSCOHost),
      PubMed, MEDLINE (Ovid), PsycINFO (EBSCOHost), Embase (Ovid) and CINAHL
      (EBSCOHost). DESIGN: A random effects meta-analysis was performed to evaluate the
      difference in EE estimates between activity monitors and criterion measurements.
      Moderator analyses were conducted to determine the benefit of additional sensors
      and to compare the accuracy of devices used for research purposes with
      commercially available devices. ELIGIBILITY CRITERIA: We included studies
      validating EE estimates from wrist-worn or arm-worn activity monitors against
      criterion measures (indirect calorimetry, room calorimeters and doubly labelled
      water) in healthy adult populations. RESULTS: 60 studies (104 effect sizes) were
      included in the meta-analysis. Devices showed variable accuracy depending on
      activity type. Large and significant heterogeneity was observed for many devices
      (I2 >75%). Combining heart rate or heat sensing technology with accelerometry
      decreased the error in most activity types. Research-grade devices were
      statistically more accurate for comparisons of total EE but less accurate than
      commercial devices during ambulatory activity and sedentary tasks. CONCLUSIONS:
      EE estimates from wrist and arm-worn devices differ in accuracy depending on
      activity type. Addition of physiological sensors improves estimates of EE, and
      research-grade devices are superior for total EE. These data highlight the need
      to improve estimates of EE from wearable devices, and one way this can be
      achieved is with the addition of heart rate to accelerometry.
      PROSPEROREGISTRATION NUMBER: CRD42018085016.

PMID- 30194222
TI  - Analysis of water polo injuries during 8904 player matches at FINA World
      Championships and Olympic games to make the sport safer.
AB  - OBJECTIVE: To analyse injuries of water polo players reported during four Summer
      Olympic Games (2004, 2008, 2012, 2016) and four Federation Internationale de
      Natation World Championships (2009, 2013, 2015, 2017). METHODS: Injuries during
      training and matches were reported daily by the team physicians and the local
      medical staff at the sports venues using an established surveillance system.
      RESULTS: A total of 381 injuries were reported, equivalent to 14.1 injuries per
      100 players (95% CI +/-1.42). The most frequent diagnoses were laceration (12.7%)
      and contusion (10.9%) of head, followed by (sub-)luxation/sprain of hand (9.5%)
      and contusion of trunk (6.5%) or hand (6.2%). More than half of the injuries
      (57.0%) occurred due to contact with another player. A quarter of the injuries
      (25.4%) were expected to result in absence from training or match; 10 (2.9%)
      resulted in an estimated time-loss of 3 or more weeks. About three-quarters of
      injuries (75.6%) occurred during matches, 86 during training. The incidence of
      match injuries was on average 56.2 injuries per 1000 match hours (95% CI +/
      6.74). The incidence of time-loss match injuries (14.7; 95% CI +/-3.44) was
      significantly higher in men than in women. CONCLUSIONS: A critical review of
      water polo in-competition rules and the implementation of a Fair Play programme
      may help to mitigate the high incidence of contact injuries incurred during
      matches. A water polo-specific concussion education programme including
      recognition, treatment and return to play is recommended. Finally, a prospective
      injury surveillance programme would help to better define water polo injuries
      outside of the competition period.

PMID- 30194223
TI  - Pain relief after musculoskeletal trauma.

PMID- 30194224
TI  - Arthrogenic muscle inhibition after ACL reconstruction: a scoping review of the
      efficacy of interventions.
AB  - OBJECTIVE: To determine whether reported therapeutic interventions for
      arthrogenic muscle inhibition (AMI) in patients with ACL injuries, following ACL
      reconstruction, or in laboratory studies of AMI, are effective in improving
      quadriceps activation failure when compared with standard therapy in control
      groups. DESIGN: A scoping review of the efficacy of interventions was conducted
      in accordance with the methodological framework of Arksey and O'Malley and the
      Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.
      Search terms included 'arthrogenic muscle inhibition', 'quadriceps activation
      following knee injuries', 'anterior cruciate' or 'knee' combined with 'quadriceps
      activation', 'quadriceps inhibition', 'corticomotor', 'arthrogenic', 'brain
      activation' and 'neuroplasticity'. Articles were evaluated for risk of bias using
      the PEDro (Physiotherapy Evidence Database) criteria. The overall quality of
      evidence for each intervention was assessed using Grading of Recommendations
      Assessment, Development and Evaluation (GRADE). DATA SOURCES: PubMed, EMBASE and
      Cumulative Index to Nursing and Allied Health Literature databases. ELIGIBILITY
      CRITERIA FOR SELECTING STUDIES: Isolated case reports and articles reporting
      outcomes in patients with chronic disease or major trauma were excluded. All
      other original research articles were included. RESULTS: 780 potential articles
      were identified. 20 met the inclusion criteria. These studies provided a moderate
      quality of evidence to support the efficacy of cryotherapy and physical exercises
      in the management of AMI. There was low-quality evidence for efficacy of
      neuromuscular electrical stimulation and transcutaneous electrical nerve
      stimulation, and very low-quality evidence for efficacy of ultrasound and
      vibration. CONCLUSIONS: This scoping review demonstrated moderate-quality
      evidence for the efficacy of cryotherapy and physical exercises in improving
      quadriceps activation failure after ACL injury and reconstruction. These
      therapeutic modalities are therefore recommended in the management of AMI.

PMID- 30194225
TI  - Make it REAL: four simple points to increase clinical relevance in sport and
      exercise medicine research.

PMID- 30194226
TI  - How key intermediary organisations 'bridge the gap' between injury prevention
      research and practice: novel insights.

PMID- 30194228
TI  - UK medical students should be taught how to manage unwanted pregnancy.

PMID- 30194227
TI  - Two-Year Observational Study of Bloodstream Infection Rates in Hemodialysis
      Facility Patients with and without Catheters.
AB  - BACKGROUND AND OBJECTIVES: Bloodstream infection rates of patients on
      hemodialysis with catheters are greater than with other vascular accesses and are
      an important quality measure. Our goal was to compare relative bloodstream
      infection rates of patients with and without catheters as a quality parameter
      among the facilities providing hemodialysis. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: We used CROWNWeb and National Healthcare Safety Network data from
      all 179 Medicare facilities providing adult outpatient hemodialysis in New
      England for >6 months throughout 2015-2016 (mean, 12,693 patients per month).
      There was a median of 60 (interquartile range, 43-93) patients per facility, with
      17% having catheters. RESULTS: Among the five batch-submitting dialysis
      organizations, the bloodstream infection rate in patients with a catheter in four
      organizations had adjusted risk ratios of 1.44 (95% confidence interval, 1.07 to
      1.93) to 1.91 (95% confidence interval, 1.39 to 2.63) times relative to the
      reference dialysis provider group (P<0.001). The percentage of catheters did not
      explain the difference in bloodstream infection rates among dialysis provider
      organizations. The bloodstream infection rates in patients with a catheter were
      negatively correlated with the facility's proportion of this patient group.
      Facilities with <10%, 10%-14.9%, 15%-19.9%, and >=20% catheter patients had
      bloodstream infection rates of 4.4, 2.2, 1.9, and 1.5 per 100 patient-months,
      respectively, in that patient group (adjusted P<0.001). This difference was not
      seen in patients without catheters. There was no effect of facility patient
      census or season of the year. CONCLUSIONS: A study of the adult outpatient
      hemodialysis facilities in New England in 2015-2016 found that four dialysis
      provider groups had significantly higher bloodstream infection rates in patients
      with a catheter than the best-performing dialysis provider group. Hemodialysis
      facilities with lower proportions of patients with a catheter have significantly
      higher bloodstream infection rates in this patient group than facilities with
      >20% catheters, a finding that did not explain the difference among provider
      organizations.

PMID- 30194230
TI  - Gravitational allocation on the sphere.
AB  - Given a collection L of n points on a sphere [Formula: see text] of surface area
      n, a fair allocation is a partition of the sphere into n parts each of area 1,
      and each is associated with a distinct point of L. We show that, if the n points
      are chosen uniformly at random and if the partition is defined by a certain
      "gravitational" potential, then the expected distance between a point on the
      sphere and the associated point of L is [Formula: see text] We use our result to
      define a matching between two collections of n independent and uniform points on
      the sphere and prove that the expected distance between a pair of matched points
      is [Formula: see text], which is optimal by a result of Ajtai, Komlos, and
      Tusnady.

PMID- 30194229
TI  - Structural basis for murine norovirus engagement of bile acids and the CD300lf
      receptor.
AB  - Murine norovirus (MNoV) is closely related to human norovirus (HNoV), an
      infectious agent responsible for acute gastroenteritis worldwide. Here we report
      the X-ray crystal structure of the dimeric MNoV VP1 protruding (P) domain in
      complex with its cellular receptor CD300lf. CD300lf binds the P domain with a 2:2
      stoichiometry, engaging a cleft between the AB and DE loops of the P2 subdomain
      at a site that overlaps the epitopes of neutralizing antibodies. We also identify
      that bile acids are cofactors enhancing MNoV cell-binding and infectivity.
      Structures of CD300lf-P domain in complex with glycochenodeoxycholic acid (GCDCA)
      and lithocholic acid (LCA) reveal two bile acid binding sites at the P domain
      dimer interface distant from receptor binding sites. The structural determinants
      for receptor and bile acid binding are supported by numerous biophysical assays
      utilizing interface residue mutations. We find that the monomeric affinity of
      CD300lf for the P domain is low and is divalent cation dependent. We have also
      determined the crystal structure of CD300lf in complex with phosphocholine,
      revealing that MNoV engages its receptor in a manner mimicking host ligands
      including similar metal coordination. Docking of the cocomplex structures onto a
      cryo-EM-derived model of MNoV suggests that each virion can make multiple CD300lf
      engagements, and thus, infection may be driven by the avidity of cell surface
      clustered CD300lf. These studies identify multiple potential modulators of
      norovirus infection that may act to regulate the interaction between the viral
      capsid P domain and its cognate cellular receptor.

PMID- 30194231
TI  - Macrocycle ring deformation as the secondary design principle for light
      harvesting complexes.
AB  - Natural light-harvesting is performed by pigment-protein complexes, which collect
      and funnel the solar energy at the start of photosynthesis. The identity and
      arrangement of pigments largely define the absorption spectrum of the antenna
      complex, which is further regulated by a palette of structural factors. Small
      alterations are induced by pigment-protein interactions. In light-harvesting
      systems 2 and 3 from Rhodoblastus acidophilus, the pigments are arranged
      identically, yet the former has an absorption peak at 850 nm that is blue-shifted
      to 820 nm in the latter. While the shift has previously been attributed to the
      removal of hydrogen bonds, which brings changes in the acetyl moiety of the
      bacteriochlorophyll, recent work has shown that other mechanisms are also
      present. Using computational and modeling tools on the corresponding crystal
      structures, we reach a different conclusion: The most critical factor for the
      shift is the curvature of the macrocycle ring. The bending of the planar part of
      the pigment is identified as the second-most important design principle for the
      function of pigment-protein complexes-a finding that can inspire the design of
      novel artificial systems.

PMID- 30194232
TI  - Functional characterization of reappearing B cells after anti-CD20 treatment of
      CNS autoimmune disease.
AB  - The anti-CD20 antibody ocrelizumab, approved for treatment of multiple sclerosis,
      leads to rapid elimination of B cells from the blood. The extent of B cell
      depletion and kinetics of their recovery in different immune compartments is
      largely unknown. Here, we studied how anti-CD20 treatment influences B cells in
      bone marrow, blood, lymph nodes, and spleen in models of experimental autoimmune
      encephalomyelitis (EAE). Anti-CD20 reduced mature B cells in all compartments
      examined, although a subpopulation of antigen-experienced B cells persisted in
      splenic follicles. Upon treatment cessation, CD20+ B cells simultaneously
      repopulated in bone marrow and spleen before their reappearance in blood. In EAE
      induced by native myelin oligodendrocyte glycoprotein (MOG), a model in which B
      cells are activated, B cell recovery was characterized by expansion of mature,
      differentiated cells containing a high frequency of myelin-reactive B cells with
      restricted B cell receptor gene diversity. Those B cells served as efficient
      antigen-presenting cells (APCs) for activation of myelin-specific T cells. In MOG
      peptide-induced EAE, a purely T cell-mediated model that does not require B
      cells, in contrast, reconstituting B cells exhibited a naive phenotype without
      efficient APC capacity. Our results demonstrate that distinct subpopulations of B
      cells differ in their sensitivity to anti-CD20 treatment and suggest that
      differentiated B cells persisting in secondary lymphoid organs contribute to the
      recovering B cell pool.

PMID- 30194233
TI  - Pendular alignment and strong chemical binding are induced in helium dimer
      molecules by intense laser fields.
AB  - Intense pulsed-laser fields have provided means to both induce spatial alignment
      of molecules and enhance strength of chemical bonds. The duration of the laser
      field typically ranges from hundreds of picoseconds to a few femtoseconds.
      Accordingly, the induced "laser-dressed" properties can be adiabatic, existing
      only during the pulse, or nonadiabatic, persisting into the subsequent field-free
      domain. We exemplify these aspects by treating the helium dimer, in its ground
      [Formula: see text] and first excited [Formula: see text] electronic states. The
      ground-state dimer when field-free is barely bound, so very responsive to
      electric fields. We examine two laser realms, designated (I) "intrusive" and (II)
      "impelling." I employs intense nonresonant laser fields, not strong enough to
      dislodge electrons, yet interact with the dimer polarizability to induce binding
      and pendular states in which the dimer axis librates about the electric field
      direction. II employs superintense high-frequency fields that impel the electrons
      to undergo quiver oscillations, which interact with the intrinsic Coulomb forces
      to form an effective binding potential. The dimer bond then becomes much
      stronger. For I, we map laser-induced pendular alignment within the X state,
      which is absent for the field-free dimer. For II, we evaluate vibronic
      transitions from the X to A states, governed by the amplitude of the quiver
      oscillations.

PMID- 30194236
TI  - Profile of Yuval Peres.

PMID- 30194234
TI  - Radioactive (90Y) upconversion nanoparticles conjugated with recombinant targeted
      toxin for synergistic nanotheranostics of cancer.
AB  - We report combined therapy using upconversion nanoparticles (UCNP) coupled to two
      therapeutic agents: beta-emitting radionuclide yttrium-90 (90Y) fractionally
      substituting yttrium in UCNP, and a fragment of the exotoxin A derived from
      Pseudomonas aeruginosa genetically fused with a targeting designed ankyrin repeat
      protein (DARPin) specific to HER2 receptors. The resultant hybrid complex UCNP-R
      T was tested using human breast adenocarcinoma cells SK-BR-3 overexpressing HER2
      receptors and immunodeficient mice, bearing HER2-positive xenograft tumors. The
      photophysical properties of UCNPs enabled background-free imaging of the UCNP-R-T
      distribution in cells and animals. Specific binding and uptake of UCNP complexes
      in SK-BR-3 cells was observed, with separate 90Y- and PE40-induced cytotoxic
      effects characterized by IC50 140 MUg/mL (UCNP-R) and 5.2 MUg/mL (UCNP-T),
      respectively. When both therapeutic agents were combined into UCNP-R-T, the
      synergetic effect increased markedly, ~2200-fold, resulting in IC50 = 0.0024
      MUg/mL. The combined therapy with UCNP-R-T was demonstrated in vivo.

PMID- 30194235
TI  - Mutually inhibitory Ras-PI(3,4)P2 feedback loops mediate cell migration.
AB  - Signal transduction and cytoskeleton networks in a wide variety of cells display
      excitability, but the mechanisms are poorly understood. Here, we show that during
      random migration and in response to chemoattractants, cells maintain
      complementary spatial and temporal distributions of Ras activity and
      phosphatidylinositol (3,4)-bisphosphate [PI(3,4)P2]. In addition, depletion of
      PI(3,4)P2 by disruption of the 5-phosphatase, Dd5P4, or by recruitment of 4
      phosphatase INPP4B to the plasma membrane, leads to elevated Ras activity, cell
      spreading, and altered migratory behavior. Furthermore, RasGAP2 and RapGAP3 bind
      to PI(3,4)P2, and the phenotypes of cells lacking these genes mimic those with
      low PI(3,4)P2 levels, providing a molecular mechanism. These findings suggest
      that Ras activity drives PI(3,4)P2 down, causing the PI(3,4)P2-binding GAPs to
      dissociate from the membrane, further activating Ras, completing a positive
      feedback loop essential for excitability. Consistently, a computational model
      incorporating such a feedback loop in an excitable network model accurately
      simulates the dynamic distributions of active Ras and PI(3,4)P2 as well as cell
      migratory behavior. The mutually inhibitory Ras-PI(3,4)P2 mechanisms we uncovered
      here provide a framework for Ras regulation that may play a key role in many
      physiological processes.

PMID- 30194237
TI  - Structural conditions on complex networks for the Michaelis-Menten input-output
      response.
AB  - The Michaelis-Menten (MM) fundamental formula describes how the rate of enzyme
      catalysis depends on substrate concentration. The familiar hyperbolic
      relationship was derived by timescale separation for a network of three
      reactions. The same formula has subsequently been found to describe steady-state
      input-output responses in many biological contexts, including single-molecule
      enzyme kinetics, gene regulation, transcription, translation, and force
      generation. Previous attempts to explain its ubiquity have been limited to
      networks with regular structure or simplifying parametric assumptions. Here, we
      exploit the graph-based linear framework for timescale separation to derive
      general structural conditions under which the MM formula arises. The conditions
      require a partition of the graph into two parts, akin to a "coarse graining" into
      the original MM graph, and constraints on where and how the input variable
      occurs. Other features of the graph, including the numerical values of
      parameters, can remain arbitrary, thereby explaining the formula's ubiquity. For
      systems at thermodynamic equilibrium, we derive a necessary and sufficient
      condition. For systems away from thermodynamic equilibrium, especially those with
      irreversible reactions, distinct structural conditions arise and a general
      characterization remains open. Nevertheless, our results accommodate, in much
      greater generality, all examples known to us in the literature.

PMID- 30194239
TI  - Inception of early-life allergen-induced airway hyperresponsiveness is reliant on
      IL-13+CD4+ T cells.
AB  - Airway hyperresponsiveness (AHR) is a critical feature of wheezing and asthma in
      children, but the initiating immune mechanisms remain unconfirmed. We demonstrate
      that both recombinant interleukin-33 (rIL-33) and allergen [house dust mite (HDM)
      or Alternaria alternata] exposure from day 3 of life resulted in significantly
      increased pulmonary IL-13+CD4+ T cells, which were indispensable for the
      development of AHR. In contrast, adult mice had a predominance of pulmonary
      LinnegCD45+CD90+IL-13+ type 2 innate lymphoid cells (ILC2s) after administration
      of rIL-33. HDM exposure of neonatal IL-33 knockout (KO) mice still resulted in
      AHR. However, neonatal CD4creIL-13 KO mice (lacking IL-13+CD4+ T cells) exposed
      to allergen from day 3 of life were protected from AHR despite persistent
      pulmonary eosinophilia, elevated IL-33 levels, and IL-13+ ILCs. Moreover,
      neonatal mice were protected from AHR when inhaled Acinetobacter lwoffii (an
      environmental bacterial isolate found in cattle farms, which is known to protect
      from childhood asthma) was administered concurrent with HDM. A. lwoffii blocked
      the expansion of pulmonary IL-13+CD4+ T cells, whereas IL-13+ ILCs and IL-33
      remained elevated. Administration of A. lwoffii mirrored the findings from the
      CD4creIL-13 KO mice, providing a translational approach for disease protection in
      early life. These data demonstrate that IL-13+CD4+ T cells, rather than IL-13+
      ILCs or IL-33, are critical for inception of allergic AHR in early life.

PMID- 30194238
TI  - Distinct Roles of Non-Overlapping Surface Regions of the Coiled-Coil Domain in
      the Potato Immune Receptor Rx1.
AB  - The intracellular immune receptor Rx1 of potato (Solanum tuberosum), which
      confers effector-triggered immunity to Potato virus X, consists of a central
      nucleotide-binding domain (NB-ARC) flanked by a carboxyl-terminal leucine-rich
      repeat (LRR) domain and an amino-terminal coiled-coil (CC) domain. Rx1 activity
      is strictly regulated by interdomain interactions between the NB-ARC and LRR, but
      the contribution of the CC domain in regulating Rx1 activity or immune signaling
      is not fully understood. Therefore, we used a structure-informed approach to
      investigate the role of the CC domain in Rx1 functionality. Targeted mutagenesis
      of CC surface residues revealed separate regions required for the intramolecular
      and intermolecular interaction of the CC with the NB-ARC-LRR and the cofactor Ran
      GTPase-activating protein2 (RanGAP2), respectively. None of the mutant Rx1
      proteins was constitutively active, indicating that the CC does not contribute to
      the autoinhibition of Rx1 activity. Instead, the CC domain acted as a modulator
      of downstream responses involved in effector-triggered immunity. Systematic
      disruption of the hydrophobic interface between the four helices of the CC
      enabled the uncoupling of cell death and disease resistance responses. Moreover,
      a strong dominant negative effect on Rx1-mediated resistance and cell death was
      observed upon coexpression of the CC alone with full-length Rx1 protein, which
      depended on the RanGAP2-binding surface of the CC. Surprisingly, coexpression of
      the N-terminal half of the CC enhanced Rx1-mediated resistance, which further
      indicated that the CC functions as a scaffold for downstream components involved
      in the modulation of disease resistance or cell death signaling.

PMID- 30194240
TI  - Recording the wild lives of immune cells.
AB  - Intravital microscopic imaging can uncover fundamental aspects of immune cell
      behavior in real time in both healthy and pathological states. Here, we discuss
      approaches for single-cell imaging of adaptive and innate immune cells to explore
      how they migrate, communicate, and mediate regulatory or effector functions in
      various tissues throughout the body. We further review how intravital single-cell
      imaging can be used to study drug effects on immune cells.

PMID- 30194242
TI  - One, two, three-how many cells for me?
AB  - An alternate strategy is described for enumerating peripheral immune cells in
      health and disease by epigenetic quantitative PCR.

PMID- 30194243
TI  - Colitis interruptus: LAGing gut inflammation.
AB  - Regulatory T cells indirectly suppress ILC3-driven colitis by suppressing gut
      resident macrophages in a LAG-3-dependent manner.

PMID- 30194244
TI  - Preprints and the implications for subsequent peer review and publishing.

PMID- 30194241
TI  - Clonal expansion of vaccine-elicited T cells is independent of aerobic
      glycolysis.
AB  - In contrast to responses against infectious challenge, T cell responses induced
      via adjuvanted subunit vaccination are dependent on interleukin-27 (IL-27). We
      show that subunit vaccine-elicited cellular responses are also dependent on IL
      15, again in contrast to the infectious response. Early expression of interferon
      regulatory factor 4 (IRF4) was compromised in either IL-27- or IL-15-deficient
      environments after vaccination but not infection. Because IRF4 facilitates
      metabolic support of proliferating cells via aerobic glycolysis, we expected this
      form of metabolic activity to be reduced in the absence of IL-27 or IL-15
      signaling after vaccination. Instead, metabolic flux analysis indicated that
      vaccine-elicited T cells used only mitochondrial function to support their clonal
      expansion. Loss of IL-27 or IL-15 signaling during vaccination resulted in a
      reduction in mitochondrial function, with no corresponding increase in aerobic
      glycolysis. Consistent with these observations, the T cell response to
      vaccination was unaffected by in vivo treatment with the glycolytic inhibitor 2
      deoxyglucose, whereas the response to viral challenge was markedly lowered.
      Collectively, our data identify IL-27 and IL-15 as critical to vaccine-elicited T
      cell responses because of their capacity to fuel clonal expansion through a
      mitochondrial metabolic program previously thought only capable of supporting
      quiescent naive and memory T cells.

PMID- 30194245
TI  - A dozen years of evolution of neurology clerkships in the United States: Looking
      up.
AB  - OBJECTIVE: To report a 2017 survey of all US medical school neurology clerkship
      directors (CDs) and to compare the results to similar surveys conducted in 2005
      and 2012. METHODS: An American Academy of Neurology (AAN) Consortium of Neurology
      Clerkship Directors (CNCD) workgroup developed the survey that was sent to all
      neurology CDs listed in the AAN CNCD database. Comparisons were made to similar
      2005 and 2012 surveys. RESULTS: The response rate was 92 of 146 programs (63%).
      Among the responding institutions, neurology is required in 94% of schools and is
      4 weeks in length in 75%. From 2005 to 2017, clerkships shifted out of a fourth
      year-only rotation (p = 0.035) to earlier curricular time points. CD protected
      time averages 0.24 full-time equivalent (FTE), with 31% of CDs reporting 0.26 to
      0.50 FTE support, a >4-fold increase from prior surveys (p < 0.001). CD service
      of >12 years increased from 9% in 2005 to 23% in 2017. Twenty-seven percent also
      serve as division chief/director, and 22% direct a preclinical neuroscience
      course. Forty-nine percent of CDs are very satisfied in their role, increased
      from 34% in 2012 (p = 0.046). The majority of CDs identify as white and male,
      with none identifying as black/African American. CONCLUSION: Changes since 2005
      and 2012 include shifting of the neurology clerkship to earlier in the medical
      school curriculum and an increase in CD salary support. CDs are more satisfied
      than reflected in previous surveys and stay in the role longer. There is a lack
      of racial diversity among neurology CDs.

PMID- 30194246
TI  - 2017 Program Director Survey: Feedback from your adult neurology residency
      leadership.
AB  - OBJECTIVE: To survey adult neurology program directors (PDs) and inform the
      future development of neurology training programs. METHODS: All US adult
      neurology PDs were invited to complete the survey. The goals were to determine
      the demographic makeup of residency programs, characterize curricula, understand
      PD and program needs, and compare results to those of a similar survey in 2007.
      RESULTS: The response rate was 70.6%. PD demographics for age, faculty track
      status, and academic rank remain unchanged over the last decade. The proportion
      of female PDs and assistant PDs has increased significantly. The mean number of
      residents per training program has also increased significantly. Female PDs are
      more likely to have a junior academic rank than their male colleagues.
      Disparities remain between the PDs' time spent on teaching/program administration
      and salary support. Most PDs support moving fellowship applications later in the
      training cycle. The majority of PDs find the Clinical Competency Committee
      process useful in assessing resident competence. A minority of PDs feel that the
      Accreditation Council for Graduate Medical Education Milestones meet their
      intended purpose. Half of programs include a curriculum to supplement the
      clinical experience on child neurology rotations. A third of programs include a
      supplemental curriculum for psychiatry rotations. The majority of programs offer
      a general fund for residents to use to support their education. CONCLUSION:
      Deficiencies exist in compensation for PDs' teaching and administrative time and
      for academic promotion for female PDs. These results serve as a benchmark for
      comparison across programs and the basis to advocate for further improvements and
      support for neurology residency training.

PMID- 30194247
TI  - Retinal vasculopathy with cerebral leukoencephalopathy (RVCL): A rare mimic of
      tumefactive MS.
AB  - OBJECTIVE: We report a series of 2 brothers who each developed tumefactive brain
      lesions, initially thought to have brain tumors or tumefactive multiple sclerosis
      (MS), but who were ultimately diagnosed with a rare autosomal dominant condition
      known as retinal vasculopathy with cerebral leukoencephalopathy (RVCL). METHODS:
      Case series and literature review. RESULTS: We present 2 brothers who developed
      tumefactive right frontal brain lesions leading to gait disturbances and
      cognitive changes. Both brothers also had nonspecific brain calcifications and T2
      hyperintense lesions, and both had ophthalmic and liver disease of unclear
      etiology. The first brother had been extensively evaluated by various
      specialists, underwent inconclusive brain and liver biopsies, and was ultimately
      unsuccessfully treated for a diagnosis of tumefactive MS. The second brother also
      underwent unrevealing evaluation with CSF analysis and brain biopsy. Further
      family history revealed that the patients' father developed a tumefactive brain
      lesion in the 1980s and had been diagnosed with CNS vasculitis. Given the
      familial link, RVCL was suspected, and genetic analysis confirmed the diagnosis
      with a 3-prime repair exonuclease 1 (TREX1) C-terminal mutation. CONCLUSION: The
      presence of tumefactive brain lesions, nonspecific brain calcifications, liver
      disease, and retinal vasculopathy, coupled with suggestive family history, led to
      the RVCL diagnosis. This report contributes to the limited understanding of RVCL,
      which can cause brain lesions that mimic gliomas or tumefactive MS. Recognition
      of this entity may prevent unnecessary invasive procedures and inappropriate
      therapeutic interventions, and would allow for proper counseling of family
      members.

PMID- 30194248
TI  - Complaints about primary care services increased by 4.5% last year.

PMID- 30194249
TI  - Head width influences flow sensing by the lateral line canal system in fishes.
AB  - The architecture of the cephalic lateral line canal system, with distinct lines
      for the supraorbital, infraorbital and mandibular canals, is highly conserved
      among fish species. Because these canals lie on a cranial platform, the sensory
      input they receive is expected to change based on how flow interacts with the
      head and how the canal pores are spatially distributed. In this study, we
      explored how head width, a trait that can vary greatly between species and across
      ontogeny, affects flow sensing. We inserted pressure sensors into physical fish
      head models of varying widths (narrow, intermediate and wide) and placed these
      models in steady and vortical flows. We measured sensory performance in terms of
      detecting flow parameters (flow speed, vortex shedding frequency and cylinder
      diameter), sensitivity (change in pressure gradient as a function of flow speed)
      and signal-to-noise ratio (SNR; strength of vortex shedding frequency with
      respect to background). Our results show that in all model heads the amount of
      hydrodynamic information was maximized at the anterior region regardless of what
      metric we used to evaluate the sensory performance. In addition, we discovered
      that all model heads had the highest SNR for vortices at the intermediate flow
      speeds but that each head width passively optimized the SNR for different sized
      vortices, which may have implications for refuge and prey seeking. Our results
      provide insight into the sensory ecology of fishes and have implications for the
      design of autonomous underwater vehicles.

PMID- 30194250
TI  - Differences in motor cortical control of the soleus and tibialis anterior.
AB  - The tibialis anterior (TA) and the soleus (SOL) are ankle joint muscles with
      functionally very different tasks. Thus, differences in motor cortical control
      between the TA and the SOL have been debated. This study compared the activity of
      the primary motor cortex during dynamic plantarflexions and dorsiflexions and
      compared this with measures obtained during rest. Single- and paired-pulse
      transcranial magnetic stimulations known as short-interval intracortical
      inhibition (SICI) were applied to the cortical representation of either the SOL
      or the TA muscle. The results show that the range of SICI from rest to activity
      is significantly greater in the TA than in the SOL. Furthermore, when the TA acts
      as the agonist during dorsiflexions of the ankle, SICI is almost absent (2.9%).
      When acting as the antagonist during plantarflexions, intracortical inhibition is
      significantly increased (28.7%). This task-specific modulation is far less
      pronounced in the SOL, which displayed higher levels of SICI when acting as the
      agonist (10.9%) during plantarflexion, but there was no significant inhibition
      (6.5%) as the antagonist during dorsiflexion. Furthermore, the cortical silent
      period (CSP) during plantarflexions was significantly longer in the SOL than in
      the TA during dorsiflexions, accompanied by a greater corticospinal excitability
      in the TA. Thus, cortical control considerably differs between the SOL and the TA
      in a way that inhibitory cortical control (SICI and CSP) of the TA is task
      specifically adapted in a broader range of movements, whereas inhibition in the
      SOL muscle is less specific and more limited in its magnitude of modulation.

PMID- 30194251
TI  - Controlled feeding experiments with diets of different abrasiveness reveal slow
      development of mesowear signal in goats (Capra aegagrus hircus).
AB  - Dental mesowear is applied as a proxy to determine the general diet of mammalian
      herbivores based on tooth-cusp shape and occlusal relief. Low, blunt cusps are
      considered typical of grazers and high, sharp cusps typical of browsers. However,
      how internal or external abrasives impact mesowear, and the time frame the wear
      signature takes to develop, still need to be explored. Four different pelleted
      diets of increasing abrasiveness (lucerne, grass, grass and rice husks, and
      grass, rice husks and sand) were fed to four groups of a total of 28 adult goats
      in a controlled feeding experiment over a 6-month period. Tooth morphology was
      captured by medical CT scans at the beginning and end of the experiment. These
      scans, as well as the crania obtained post mortem, were scored using the mesowear
      method. Comparisons between diet groups showed few significant differences after
      6 months, irrespective of whether CT scans or the real teeth were scored. Only
      when assessing the difference in signal between the beginning and the end of the
      experiment did relevant, significant diet-specific effects emerge. Diets
      containing lower phytolith content caused a more pronounced change in mesowear
      towards sharper cusps/higher reliefs, while the feed containing sand did not
      result in more extreme changes in mesowear when compared with the same feed
      without sand. Our experiment suggests that the formation of a stable and hence
      reliable mesowear signal requires more time to develop than 6 months.

PMID- 30194252
TI  - Aquatic versus terrestrial crab skeletal support: morphology, mechanics, molting
      and scaling.
AB  - The transition from aquatic to terrestrial environments places significant
      mechanical challenges on skeletal support systems. Crabs have made this
      transition multiple times and are the largest arthropods to inhabit both
      environments. Furthermore, they alternate between rigid and hydrostatic
      skeletons, making them an interesting system to examine mechanical adaptations in
      skeletal support systems. I hypothesized that terrestrial crabs have modified
      morphology to enhance mechanical stiffness and that rigid and hydrostatic
      skeletons scale differently from each other, with stronger allometric
      relationships on land. Using the aquatic blue crab, Callinectes sapidus, and the
      terrestrial blackback land crab, Gecarcinus lateralis, I measured and compared
      body mass, merus morphology (dimensions, cuticle thickness and the second moment
      of area I) and mechanics (flexural stiffness EI, elastic modulus E, critical
      stress and hydrostatic pressure) of rigid and hydrostatic stage crabs
      encompassing a range of sizes (C. sapidus: 1.5-133 g, N<=24; G. lateralis: 22-70
      g, N<=15). The results revealed that rigid G. lateralis has similar morphology
      (limb length to diameter L/D and cuticle thickness to limb diameter T/D ratio) to
      C. sapidus, and the mechanics and most scaling relationships are the same.
      Hydrostatic land crabs differ from aquatic crabs by having different morphology
      (thinner cuticle), mechanics (greater internal pressures) and scaling
      relationship (cuticle thickness). These results suggest that the rigid crab body
      plan is inherently overbuilt and sufficient to deal with the greater
      gravitational loading that occurs on land, while mechanical adaptations are
      important for hydrostatically supported crabs. Compared with other arthropods and
      hydrostatic animals, crabs possess distinct strategies for adapting mechanically
      to life on land.

PMID- 30194253
TI  - Virtual reality distraction from painful procedures in the paediatric emergency
      department.

PMID- 30194254
TI  - Genome-wide association study implicates immune dysfunction in the development of
      Hodgkin lymphoma.
AB  - To further our understanding of inherited susceptibility to Hodgkin lymphoma
      (HL), we performed a meta-analysis of 7 genome-wide association studies totaling
      5325 HL cases and 22 423 control patients. We identify 5 new HL risk loci at
      6p21.31 (rs649775; P = 2.11 * 10-10), 6q23.3 (rs1002658; P = 2.97 * 10-8),
      11q23.1 (rs7111520; P = 1.44 * 10-11), 16p11.2 (rs6565176; P = 4.00 * 10-8), and
      20q13.12 (rs2425752; P = 2.01 * 10-8). Integration of gene expression, histone
      modification, and in situ promoter capture Hi-C data at the 5 new and 13 known
      risk loci implicates dysfunction of the germinal center reaction, disrupted T
      cell differentiation and function, and constitutive NF-kappaB activation as
      mechanisms of predisposition. These data provide further insights into the
      genetic susceptibility and biology of HL.

PMID- 30194255
TI  - Aberrant CD137 ligand expression induced by GATA6 overexpression promotes tumor
      progression in cutaneous T-cell lymphoma.
AB  - CD137 and its ligand, CD137L, are expressed on activated T cells and antigen
      presenting cells, respectively. Recent studies have shown that CD137L and CD137
      are aberrantly expressed by tumor cells, especially in some hematopoietic
      malignancies, and interactions between these molecules on tumor cells promote
      tumor growth. In this study, we investigated the roles of CD137L and CD137 in
      cutaneous T-cell lymphoma (CTCL), represented by mycosis fungoides and Sezary
      syndrome. Flow cytometric analysis showed that primary Sezary cells and CTCL cell
      lines (Hut78, MyLa, HH, SeAx, and MJ) aberrantly expressed CD137L. CD137L
      expression by tumor cells in CTCL was also confirmed by immunohistochemistry.
      Anti-CD137L-neutralizing antibody inhibited proliferation, survival, CXCR4
      mediated migration, and in vivo growth in CTCL cell lines through inhibition of
      phosphorylation of AKT, extracellular signal-regulated kinase 1/2, p38 MAPK, and
      JNK. Moreover, suppression of CD137L signaling decreased antiapoptotic proteins
      Bcl-2 and phosphorylated Bad. We also explored the transcription factor
      regulating CD137L expression. Because GATA6 has been proposed as an oncogene in
      many types of tumors with aberrant CD137L expression, we examined GATA6
      expression and the involvement of GATA6 in CD137L expression in CTCL. DNA
      hypomethylation and histone acetylation induced GATA6 overexpression in CTCL
      cells. Furthermore, chromatin immunoprecipitation, luciferase reporter assay, and
      knockdown by short hairpin RNA showed that GATA6 directly upregulated CD137L
      expression. Inhibition of GATA6 resulted in decreased survival and in vivo growth
      in CTCL cells. Collectively, our findings prompt a novel therapeutic approach to
      CTCL based on the discovery that the GATA6/CD137L axis plays an important role in
      the tumorigenesis of CTCL.

PMID- 30194256
TI  - Correction: Cyclase-associated protein 1 (CAP1) is a prenyl-binding partner of
      Rap1 GTPase.

PMID- 30194257
TI  - Correction: Cyanobacteriochrome-based photoswitchable adenylyl cyclases (cPACs)
      for broad spectrum light regulation of cAMP levels in cells.

PMID- 30194258
TI  - Walking a fine line between beta-cell secretion and proliferation.
AB  - Of the many common genetic variants associated with type 2 diabetes, that in
      TCF7L2 remains the most studied because it has the greatest effect size. However,
      the mechanism by which this variant alters diabetes risk remains elusive. A new
      study adds another layer of complexity, suggesting that the effects of TCF7L2 are
      context-dependent, and highlights a novel interaction that might bias a beta-cell
      to a secretory or proliferative phenotype. This in turn might open up new avenues
      to the restoration of insulin secretion in people with type 2 diabetes.

PMID- 30194259
TI  - Prevalence and behavioural associations of unintentional injuries among Chinese
      college students: a 50-University population-based study.
AB  - OBJECTIVE: To assess the prevalence, demographic characteristics and behavioural
      correlates of unintentional injuries among Chinese college students. METHODS: A
      cross-sectional multistage survey sampling process was conducted among 11 770
      undergraduates from 50 universities in China. Students were asked to report
      different types of unintentional injuries that required medical attention from a
      doctor over the past year. The chi2 test and multiple logistic regression
      analysis were used to identify factors associated with these injuries. RESULTS:
      The overall unintentional injury prevalence was 47.9% (95% CI 47.6% to 48.2%).
      Most injuries occurred at sport venues (24.0%), following by home/dormitory
      injuries (20.5%) and traffic injuries (13.0%). Some behavioural factors
      exhibiting significant associations with overall unintentional injuries were:
      sleeping less than 7 hours (OR=1.32, 95% CI 1.27 to 1.37), smoking (OR=1.28, 95%
      CI 1.23 to 1.32), alcohol consumption (OR=1.74, 95% CI 1.69 to 1.78) and heavy
      internet use (OR=1.60, 95% CI 1.52 to 1.67). Male students were more likely to be
      involved in traffic and sport injuries than female students. Students majoring in
      non-medical fields had a higher risk of sport and home injuries than students
      majoring in medical fields. Those who drank alcohol, slept less than 7 hours or
      who reported heavy internet use were more likely to experience all types of
      injuries than students who did not participate in these behaviours. Finally,
      students who smoked had a higher likelihood of traffic and sport injuries than
      non-smoking students. CONCLUSIONS: A substantial number of college students
      reported injuries in the past year, and several key behavioural factors were
      associated with injuries. These findings could be beneficial for the design,
      implementation and assessment of injury intervention programme with college
      students. Based on these findings, policy implications for unintentional injury
      prevention and control were also considered.

PMID- 30194261
TI  - The Arabidopsis phyB-9 Mutant Has a Second-Site Mutation in the VENOSA4 Gene That
      Alters Chloroplast Size, Photosynthetic Traits, and Leaf Growth.

PMID- 30194260
TI  - piRNAs and PIWI proteins: regulators of gene expression in development and stem
      cells.
AB  - PIWI proteins and Piwi-interacting RNAs (piRNAs) have established and conserved
      roles in repressing transposable elements (TEs) in the germline of animals.
      However, in several biological contexts, a large proportion of piRNAs are not
      related to TE sequences and, accordingly, functions for piRNAs and PIWI proteins
      that are independent of TE regulation have been identified. This aspect of piRNA
      biology is expanding rapidly. Indeed, recent reports have revealed the role of
      piRNAs in the regulation of endogenous gene expression programs in germ cells, as
      well as in somatic tissues, challenging dogma in the piRNA field. In this Review,
      we focus on recent data addressing the biological and developmental functions of
      piRNAs, highlighting their roles in embryonic patterning, germ cell
      specification, stem cell biology, neuronal activity and metabolism.

PMID- 30194262
TI  - Identification of Woodland Strawberry Gene Coexpression Networks.

PMID- 30194263
TI  - The Healing Power of Light.

PMID- 30194264
TI  - An Improved Tool for Mapping the Membrane-Associated Protein Interactome.

PMID- 30194265
TI  - Endothelial cell fitness dictates the source of regenerating liver vasculature.
AB  - Neoangiogenesis plays a key role in diverse pathophysiological conditions,
      including liver regeneration. Yet, the source of new endothelial cells (ECs)
      remains elusive. By analyzing the regeneration of the liver vasculature in
      irradiation-based myeloablative and nonmyeloablative bone marrow transplantation
      mouse models, we discovered that neoangiogenesis in livers with intact
      endothelium was solely mediated by proliferation of resident ECs. However,
      following irradiation-induced EC damage, bone marrow-derived mononuclear cells
      were recruited and incorporated into the vasculature. Further experiments with
      direct bone marrow infusion or granulocyte colony-stimulating factor (G-CSF)
      mediated progenitor cell mobilization, which resembles clinically relevant stem
      cell therapy, demonstrated that bone marrow-derived cells did not contribute to
      the regeneration of liver vasculature after two-thirds partial hepatectomy (PHx).
      Taken together, the data reconcile many of the discrepancies in the literature
      and highlight that the cellular source of regenerating endothelium depends on the
      fitness of the residual vasculature.

PMID- 30194266
TI  - Piezo1 and Gq/G11 promote endothelial inflammation depending on flow pattern and
      integrin activation.
AB  - The vascular endothelium is constantly exposed to mechanical forces, including
      fluid shear stress exerted by the flowing blood. Endothelial cells can sense
      different flow patterns and convert the mechanical signal of laminar flow into
      atheroprotective signals, including eNOS activation, whereas disturbed flow in
      atheroprone areas induces inflammatory signaling, including NF-kappaB activation.
      How endothelial cells distinguish different flow patterns is poorly understood.
      Here we show that both laminar and disturbed flow activate the same initial
      pathway involving the mechanosensitive cation channel Piezo1, the purinergic P2Y2
      receptor, and Gq/G11-mediated signaling. However, only disturbed flow leads to
      Piezo1- and Gq/G11-mediated integrin activation resulting in focal adhesion
      kinase-dependent NF-kappaB activation. Mice with induced endothelium-specific
      deficiency of Piezo1 or Galphaq/Galpha11 show reduced integrin activation,
      inflammatory signaling, and progression of atherosclerosis in atheroprone areas.
      Our data identify critical steps in endothelial mechanotransduction, which
      distinguish flow pattern-dependent activation of atheroprotective and atherogenic
      endothelial signaling and suggest novel therapeutic strategies to treat
      inflammatory vascular disorders such as atherosclerosis.

PMID- 30194267
TI  - Activated PIK3CD drives innate B cell expansion yet limits B cell-intrinsic
      immune responses.
AB  - Activated PI3K-delta syndrome (APDS) is an immunodeficiency caused by gain-of
      function mutations in PIK3CD. This disease exhibits complex immune phenotypes
      including increased IgM, recurrent infection, and impaired vaccine responses. To
      better understand the impact of B cells in this disease, we generated an
      inducible model of the common APDS mutation (hPIK3CD-E1021K; referred to as
      aPIK3CD) and intercrossed these mice with B cell-specific Cre models. Mb1-aPIK3CD
      mice exhibited bone marrow B lymphopenia and, conversely, expansion of the
      peripheral innate B1a and MZ B cell compartments. aPIK3CD B cells manifest
      increased pS6 and increased survival at several stages, without alterations in
      cycling, and baseline increases in plasma cells, natural IgM, and IgG3. Finally,
      Mb1-aPIK3CD mice exhibited blunted T cell-independent immune responses, and both
      AID- and CD21-aPIK3CD mice displayed reduced class-switched antibodies following
      T cell-dependent immunization. Thus, aPIK3CD alters B cell development and
      function and is counter-productive during immune responses, providing insight
      into B cell-intrinsic contributions to the APDS phenotype.

PMID- 30194268
TI  - Myoepithelial crowd control of cancer cells.
AB  - Smooth muscle-like cells can actively remodel epithelia, a mechanism common
      across developing tissues. In this issue, new work from Sirka et al. (2018. J.
      Cell Biol. https://doi.org/10.1083/jcb.201802144) demonstrates a novel mechanism
      for tumor suppression by smooth muscle-like myoepithelial cells of the mammary
      gland.

PMID- 30194271
TI  - The association of household fine particulate matter and kerosene with
      tuberculosis in women and children in Pune, India.
AB  - OBJECTIVES: Household air pollution (HAP) is a risk factor for respiratory
      disease, however has yet to be definitively associated with tuberculosis (TB). We
      aimed to assess the association between HAP and TB. METHODS: A matched case
      control study was conducted among adult women and children patients with TB and
      healthy controls matched on geography, age and sex. HAP was assessed using
      questionnaires for pollution sources and 24-hour household concentrations of
      particulate matter <2.5 MUm in diameter (PM2.5). RESULTS: In total, 192
      individuals in 96 matched pairs were included. The median 24-hour time-weighted
      average PM2.5 was nearly seven times higher than the WHO's recommendation of 25
      ug/m3, and did not vary between controls (179 ug/m3; IQR: 113-292) and cases
      (median 157 ug/m3; 95% CI 93 to 279; p=0.57). Reported use of wood fuel was not
      associated with TB (OR 2.32; 95% CI 0.65 to 24.20) and kerosene was significantly
      associated with TB (OR 5.49, 95% CI 1.24 to 24.20) in adjusted analysis.
      Household PM2.5 was not associated with TB in univariate or adjusted analysis.
      Controlling for PM2.5 concentration, kerosene was not significantly associated
      with TB, but effect sizes ranged from OR 4.30 (95% CI 0.78 to 30.86; p=0.09) to
      OR 5.49 (0.82 to 36.75; p=0.08). CONCLUSIONS: Use of kerosene cooking fuel is
      positively associated with TB in analysis using reported sources of exposure.
      Ubiquitously high levels of particulates limited detection of a difference in
      household PM2.5 between cases and controls.

PMID- 30194269
TI  - Intronless mRNAs transit through nuclear speckles to gain export competence.
AB  - Nuclear speckles (NSs) serve as splicing factor storage sites. In this study, we
      unexpectedly found that many endogenous intronless mRNAs, which do not undergo
      splicing, associate with NSs. These associations do not require transcription,
      polyadenylation, or the polyA tail. Rather, exonic splicing enhancers present in
      intronless mRNAs and their binding partners, SR proteins, promote intronless mRNA
      localization to NSs. Significantly, speckle targeting of mRNAs promotes the
      recruitment of the TREX export complex and their TREX-dependent nuclear export.
      Furthermore, TREX, which accumulates in NSs, is required for releasing intronless
      mRNAs from NSs, whereas NXF1, which is mainly detected at nuclear pores, is not.
      Upon NXF1 depletion, the TREX protein UAP56 loses speckle concentration but
      coaccumulates with intronless mRNAs and polyA RNAs in the nucleoplasm, and these
      RNAs are trapped in NSs upon UAP56 codepletion. We propose that the export
      competent messenger RNP assembly mainly occurs in NSs for intronless mRNAs and
      that entering NSs serves as a quality control step in mRNA export.

PMID- 30194272
TI  - Working life expectancy in good and poor self-perceived health among Dutch
      workers aged 55-65 years with a chronic disease over the period 1992-2016.
AB  - OBJECTIVES: Several governments have taken measures to encourage prolonged
      working. It is therefore likely that older adults with a chronic disease are
      required to work longer in poor self-perceived health (SPH) than before. This
      study examines to what extent working life expectancy (WLE) in good and poor SPH
      changed between 1992 and 2016 in workers with a chronic disease from age 55 years
      onwards. METHODS: Three cohorts (1992, 2002 and 2012) of workers with a chronic
      disease aged 55-65 years were selected from the Longitudinal Aging Study
      Amsterdam with a 3-year follow-up each (n=705). A three-state survival model was
      estimated, modelling transitions between states 'working with good SPH', 'working
      with poor SPH' and 'exit from work'. WLEs were estimated using Multistate
      Modelling and Estimating Life Expectancies using Continuous Time in R. RESULTS:
      Of the workers with a chronic disease, total WLEs at age 55 years were 5.2, 5.7
      and 6.8 years in cohorts 1992, 2002 and 2012, respectively. Workers initially
      having poor SPH, had total WLE of 4.7 years of which 2.4 years in poor SPH in
      cohort 1992. These workers had total WLE of 5.2 years of which 3.3 years in poor
      SPH in cohort 2002, and total WLE of 6.5 years of which 3.6 years in poor SPH in
      cohort 2012. CONCLUSIONS: Workers with a chronic disease extended their working
      lives by approximately 18 months from 1992 to 2016. In the first decade,
      unhealthy WLE increased, whereas in the second decade, healthy WLE increased,
      among both workers in general and workers initially having poor SPH.

PMID- 30194270
TI  - Mechanical principles of nuclear shaping and positioning.
AB  - Positioning and shaping the nucleus represents a mechanical challenge for the
      migrating cell because of its large size and resistance to deformation. Cells
      shape and position the nucleus by transmitting forces from the cytoskeleton onto
      the nuclear surface. This force transfer can occur through specialized linkages
      between the nuclear envelope and the cytoskeleton. In response, the nucleus can
      deform and/or it can move. Nuclear movement will occur when there is a net
      differential in mechanical force across the nucleus, while nuclear deformation
      will occur when mechanical forces overcome the mechanical resistance of the
      various structures that comprise the nucleus. In this perspective, we review
      current literature on the sources and magnitude of cellular forces exerted on the
      nucleus, the nuclear envelope proteins involved in transferring cellular forces,
      and the contribution of different nuclear structural components to the mechanical
      response of the nucleus to these forces.

PMID- 30194273
TI  - Characteristics of difficult-to-treat rheumatoid arthritis: results of an
      international survey.
AB  - OBJECTIVES: Patients with difficult-to-treat rheumatoid arthritis (RA) remain
      symptomatic despite treatment according to current European League Against
      Rheumatism (EULAR) management recommendations. These focus on early phases of the
      disease and pharmacological management. We aimed to identify characteristics of
      difficult-to-treat RA and issues to be addressed in its workup and management
      that are not covered by current management recommendations. METHODS: An
      international survey was conducted among rheumatologists with multiple-choice
      questions on disease characteristics of difficult-to-treat RA. Using open
      questions, additional items to be addressed and items missing in current
      management recommendations were identified. RESULTS: 410 respondents completed
      the survey: 50% selected disease activity score assessing 28 joints >3.2 OR
      presence of signs suggestive of active disease as characteristics of difficult-to
      treat RA; 42% selected fatigue; 48% selected failure to >=2 conventional
      synthetic disease-modifying antirheumatic drugs (DMARDs) AND >=2
      biological/targeted synthetic DMARDs; 89% selected inability to taper
      glucocorticoids below 5 mg or 10 mg prednisone equivalent daily. Interfering
      comorbidities, extra-articular manifestations and polypharmacy were identified as
      important issues missing in current management recommendations. CONCLUSIONS:
      There is wide variation in concepts of difficult-to-treat RA. Several important
      issues regarding these patients are not addressed by current EULAR
      recommendations.

PMID- 30194274
TI  - Will SPAR be useful in the usual patients with scleroderma?

PMID- 30194275
TI  - Dose reduction of baricitinib in patients with rheumatoid arthritis achieving
      sustained disease control: results of a prospective study.
AB  - OBJECTIVES: This study investigated the effects of dose step-down in patients
      with rheumatoid arthritis (RA) who achieved sustained disease control with
      baricitinib 4 mg once a day. METHODS: Patients who completed a baricitinib phase
      3 study could enter a long-term extension (LTE). In the LTE, patients who
      received baricitinib 4 mg for >=15 months and maintained CDAI low disease
      activity (LDA) or remission (REM) were blindly randomised to continue 4 mg or
      taper to 2 mg. Patients could rescue (to 4 mg) if needed. Efficacy and safety
      were assessed through 48 weeks. RESULTS: Patients in both groups maintained LDA
      (80% 4 mg; 67% 2 mg) or REM (40% 4 mg; 33% 2 mg) over 48 weeks. However, dose
      reduction resulted in small, statistically significant increases in disease
      activity at 12, 24 and 48 weeks. Dose reduction also produced earlier and more
      frequent relapse (loss of step-down criteria) over 48 weeks compared with 4 mg
      maintenance (23% 4 mg vs 37% 2 mg, p=0.001). Rescue rates were 10% for
      baricitinib 4 mg and 18% for baricitinib 2 mg. Dose reduction was associated with
      a numerically lower rate of non-serious infections (30.6 for baricitinib 4 mg vs
      24.9 for 2 mg). Rates of serious adverse events and adverse events leading to
      discontinuation were similar across groups. CONCLUSIONS: In a large randomised,
      blinded phase 3 study, maintenance of RA control following induction of sustained
      LDA/REM with baricitinib 4 mg was greater with continued 4 mg than after taper to
      2 mg. Nonetheless, most patients tapered to 2 mg could maintain LDA/REM or
      recapture with return to 4 mg if needed.

PMID- 30194276
TI  - 6-Chloro-5-[4-(1-Hydroxycyclobutyl)Phenyl]-1H-Indole-3-Carboxylic Acid is a
      Highly Selective Substrate for Glucuronidation by UGT1A1, Relative to beta
      Estradiol.
AB  - 6-Chloro-5-[4-(1-hydroxycyclobutyl)phenyl]-1H-indole-3-carboxylic acid (PF
      06409577) is a direct activator of the human beta1-containing adenosine
      monophosphate-activated protein kinase (AlphaMPK) isoforms. The clearance
      mechanism of PF-06409577 in animals and humans involves uridine
      diphosphoglucuronosyl transferase (UGT)-mediated glucuronidation to an acyl
      glucuronide metabolite of PF-06409577 [(2S,3S,4S,5R,6S)-6-((6-chloro-5-(4-(1
      hydroxycyclobutyl)phenyl)-1H-indole-3-carbonyl)oxy)-3,4,5-trihydroxytetrahydro-2H
      pyran-2-carboxylic acid (M1)], which retains selective activation of human beta1
      containing AMPK isoforms. This paper describes a detailed characterization of the
      human UGT isoform(s) responsible for glucuronidation of PF-06409577 to M1.
      Studies using a panel of 13 human recombinant UGT (hrUGT) enzymes indicated that
      PF-06409577 was converted to M1 in a highly selective fashion by UGT1A1, which
      was further verified in human liver microsomes treated with specific chemical
      inhibitors, and in different UGT1A1 expressers. Conversion of PF-06409577 to M1
      by UGT1A1 occurred in a relatively selective fashion, compared with beta
      estradiol (ES), a conventional probe substrate of UGT1A1. The Michaelis-Menten
      constant (K M) and V max values describing the formation of M1 from PF-06409577
      in hrUGT1A1 and microsomal preparations from human intestine, liver, and kidney
      ranged from 131 to 212 MUM (K M) and 107-3834 pmol/min per milligram (V max) in
      the presence of 2% bovine serum albumin. Relative activity factors (RAF) were
      determined for UGT1A1 using PF-06409577 and ES to enable estimation of intrinsic
      clearance from various tissues. RAF values from PF-06409577 and ES were generally
      comparable with the exception of intestinal microsomes, where ES overestimated
      the RAF of UGT1A1 due to glucuronidation by intestinal UGT1A8 and UGT1A10. Our
      results suggest the potential utility of PF-06409477 as a selective probe UGT1A1
      substrate for UGT reaction phenotyping and inhibition studies in preclinical
      discovery/development.

PMID- 30194277
TI  - Long-term Outcome of Resective Epilepsy Surgery in Patients With Lennox-Gastaut
      Syndrome.
AB  - OBJECTIVE: We aimed to evaluate the long-term outcome of resective epilepsy
      surgery in patients with Lennox-Gastaut syndrome (LGS). METHODS: We reviewed the
      case reports of 90 patients with LGS who had undergone resective surgery between
      2003 and 2014 at the Severance Children's Hospital and managed them for a minimum
      period of 2 years. RESULTS: At the time of surgery, the patients were between 3.0
      and 23.5 years old (mean +/- SD: 9.3 +/- 4.4). The time from seizure onset to
      surgery ranged from 0.7 to 20.1 years (7.2 +/- 4.3). On postoperative follow-up
      for an average period of 6.1 +/- 2.2 years (range: 2.1-11.4 years), 45 patients
      (50.0%) had no seizures, and 15 (16.7%) reported infrequent seizures. Seizure
      free outcomes were achieved in 15 of the 21 (71.4%) hemispherectomies, 23 of the
      51 (45.1%) multilobar resections, and 7 of the 18 (38.9%) single lobar
      resections. On high-resolution MRIs, 20 patients (22.2%) had negative findings, 8
      of whom (40.0%) became seizure-free after resective surgery. Malformation of
      cortical development was the most common pathologic finding and was noted in 57
      patients (63.3%). Seizure-free patients achieved better adaptive behavior and
      social competence than did patients with persistent seizures at the second (2-3
      years after surgery) and third (4-6 years after surgery) follow-ups, as indicated
      by social quotients (P < .05). CONCLUSIONS: Resective surgery is a viable option
      in some patients to treat seizures that are associated with LGS, with a high
      probability of seizure control and better adaptive function.

PMID- 30194278
TI  - Sertraline-Induced Rhabdomyolysis, Trismus, and Cardiac Arrest in a Child.
AB  - Selective serotonin reuptake inhibitors are a commonly used and often effective
      class of medications in the treatment of mood disorders such as anxiety and
      depression. Sertraline (1S,4S-N-methyl-4-[3,4-dichlorophenyl]-1,2,3,4-tetrahydro
      1-naphthylamine [Zoloft; Pfizer, New York City, NY]) is a frequently used
      selective serotonin reuptake inhibitor that has shown efficacy in children,
      adolescents, and adults. We report the case of a 13-year-old boy with sertraline
      induced rhabdomyolysis and renal failure, trismus, and cardiopulmonary arrest.
      Pharmacogenetic testing later revealed our patient had serotonin transporter
      polymorphisms and enzymatic alterations that put him at risk for increased levels
      of sertraline and greater likelihood for untoward side effects.

PMID- 30194279
TI  - Farnesylated heat shock protein 40 is a component of membrane-bound RISC in
      Arabidopsis.
AB  - ARGONAUTE1 (AGO1) binds directly to small regulatory RNA and is a key effector
      protein of post-transcriptional gene silencing mediated by microRNA (miRNA) and
      small interfering RNA (siRNA) in Arabidopsis The formation of an RNA-induced
      silencing complex (RISC) of AGO1 and small RNA requires the function of the heat
      shock protein 70/90 chaperone system. Some functions of AGO1 occur in association
      with endomembranes, in particular the rough endoplasmic reticulum (RER), but
      proteins interacting with AGO1 in membrane fractions remain unidentified. In this
      study, we show that the farnesylated heat shock protein 40 homologs, J2 and J3,
      associate with AGO1 in membrane fractions in a manner that involves protein
      farnesylation. We also show that three changes in AGO1 function are detectable in
      mutants in protein farnesylation and J2/J3. First, perturbations of the
      HSP40/70/90 pathway by mutation of J3, HSP90, and farnesyl transferase affect the
      amounts of AGO1 associated with membranes. Second, miRNA association with
      membrane-bound polysomes is increased in farnesyl transferase and farnesylation
      deficient J2/J3 mutants. Third, silencing by noncell autonomously acting short
      interfering RNAs is impaired. These observations highlight the involvement of
      farnesylated J2/J3 in small RNA-mediated gene regulation, and suggest that the
      importance of chaperone-AGO1 interaction is not limited to the RISC assembly
      process.

PMID- 30194280
TI  - A biochemical and genetic discovery pipeline identifies PLCdelta4b as a
      nonreceptor activator of heterotrimeric G-proteins.
AB  - Recent evidence has revealed that heterotrimeric G-proteins can be activated by
      cytoplasmic proteins that share an evolutionarily conserved sequence called the
      Galpha-binding-and-activating (GBA) motif. This mechanism provides an alternative
      to canonical activation by G-protein-coupled receptors (GPCRs) and plays
      important roles in cell function, and its dysregulation is linked to diseases
      such as cancer. Here, we describe a discovery pipeline that uses biochemical and
      genetic approaches to validate GBA candidates identified by sequence similarity.
      First, putative GBA motifs discovered in bioinformatics searches were synthesized
      on peptide arrays and probed in batch for Galphai3 binding. Then, cDNAs encoding
      proteins with Galphai3-binding sequences were expressed in a genetically-modified
      yeast strain that reports mammalian G-protein activity in the absence of GPCRs.
      The resulting GBA motif candidates were characterized by comparison of their
      biochemical, structural, and signaling properties with those of all previously
      described GBA motifs in mammals (GIV/Girdin, DAPLE, Calnuc, and NUCB2). We found
      that the phospholipase Cdelta4 (PLCdelta4) GBA motif binds G-proteins with high
      affinity, has guanine nucleotide exchange factor activity in vitro, and activates
      G-protein signaling in cells, as indicated by bioluminescence resonance energy
      transfer (BRET)-based biosensors of G-protein activity. Interestingly, the
      PLCdelta4 isoform b (PLCdelta4b), which lacks the domains required for PLC
      activity, bound and activated G-proteins more efficiently than the full-length
      isoform a, suggesting that PLCdelta4b functions as a G-protein regulator rather
      than as a PLC. In summary, we have identified PLCdelta4 as a nonreceptor
      activator of G-proteins and established an experimental pipeline to discover and
      characterize GBA motif-containing proteins.

PMID- 30194281
TI  - Phospholipase D-dependent mTOR complex 1 (mTORC1) activation by glutamine.
AB  - Glutamine is a key nutrient required for sustaining cell proliferation,
      contributing to nucleotide, protein, and lipid synthesis. The mTOR complex 1
      (mTORC1) is a highly conserved protein complex that acts as a sensor of
      nutrients, relaying signals for the shift from catabolic to anabolic metabolism.
      Although glutamine plays an important role in mTORC1 activation, the mechanism is
      not clear. Here we describe a leucine- and Rag-independent mechanism of mTORC1
      activation by glutamine that depends on phospholipase D and the production of
      phosphatidic acid, which is required for the stability and activity of mTORC1.
      The phospholipase D-dependent activation of mTORC1 by glutamine depended on the
      GTPases ADP ribosylation factor 1 (Arf1), RalA, and Rheb. Glutamine deprivation
      could be rescued by alpha-ketoglutarate, a downstream metabolite of glutamine.
      This mechanism represents a distinct nutrient input to mTORC1 that is independent
      of Rag GTPases and leucine.

PMID- 30194282
TI  - The EGF-LIKE domain of thrombospondin-4 is a key determinant in the development
      of pain states due to increased excitatory synaptogenesis.
AB  - Up-regulation of thrombospondin-4 (TSP4) or voltage-gated calcium channel subunit
      alpha2delta1 (Cavalpha2delta1) proteins in the spinal cord contributes to
      neuropathic pain development through an unidentified mechanism. We have
      previously shown that TSP4 interacts with Cavalpha2delta1 to promote excitatory
      synaptogenesis and the development of chronic pain states. However, the TSP4
      determinants responsible for these changes are not known. Here, we tested the
      hypothesis that the Cavalpha2delta1-binding domains of TSP4 are synaptogenic and
      pronociceptive. We mapped the major Cavalpha2delta1-binding domains of TSP4
      within the coiled-coil and epidermal growth factor (EGF)-like domains in vitro
      Intrathecal injection of TSP4 fragment proteins containing the EGF-like domain
      (EGF-LIKE) into naive rodents was sufficient for inducing behavioral
      hypersensitivity similar to that produced by an equal molar dose of full-length
      TSP4. Gabapentin, a drug that binds to Cavalpha2delta1, blocked EGF-LIKE-induced
      behavioral hypersensitivity in a dose-dependent manner, supporting the notion
      that EGF-LIKE interacts with Cavalpha2delta1 and thereby mediates behavioral
      hypersensitivity. This notion was further supported by our findings that a
      peptide within EGF-LIKE (EGFD355-369) could block TSP4- or Cavalpha2delta1
      induced behavioral hypersensitivity after intrathecal injections. Furthermore,
      only TSP4 proteins that contained EGF-LIKE could promote excitatory
      synaptogenesis between sensory and spinal cord neurons, which could be blocked by
      peptide EGFD355-369. Together, these findings indicate that EGF-LIKE is the
      molecular determinant that mediates aberrant excitatory synaptogenesis and
      chronic pain development. Blocking interactions between EGF-LIKE and
      Cavalpha2delta1 could be an alternative approach in designing target-specific
      pain medications.

PMID- 30194284
TI  - Multiple functionalities of molecular chaperones revealed through systematic
      mapping of their interaction networks.
AB  - Chaperones are a highly interactive group of proteins that function globally in
      many cellular processes involved in maintaining protein homeostasis. Traditional
      biochemical assays typically do not provide a complete view of the intricate
      networks through which chaperones collaborate to promote proteostasis. Recent
      advances in high-throughput systematic analyses of chaperone interactions have
      uncovered that chaperones display a remarkable cooperativity in their
      interactions with numerous client proteins. This cooperativity has been found to
      be a fundamental aspect of a properly functioning cell. Aberrant formation or
      improper regulation of these interactions can easily lead to disease states.
      Herein, we provide an overview of the use of large-scale interaction assays,
      whether physical (protein-protein) or genetic (epistatic), to study chaperone
      interaction networks. Importantly, we discuss the ongoing need for such studies
      to determine the mechanisms by which protein homeostasis is controlled in the
      cell.

PMID- 30194283
TI  - Aplysia allatotropin-related peptide and its newly identified d-amino acid
      containing epimer both activate a receptor and a neuronal target.
AB  - l- to d-residue isomerization is a post-translational modification (PTM) present
      in neuropeptides, peptide hormones, and peptide toxins from several animals. In
      most cases, the d-residue is critical for the biological function of the
      resulting d-amino acid-containing peptide (DAACP). Here, we provide an example in
      native neuropeptides in which the DAACP and its all-l-amino acid epimer are both
      active at their newly identified receptor in vitro and at a neuronal target
      associated with feeding behavior. On the basis of sequence similarity to a known
      DAACP from cone snail venom, we hypothesized that allatotropin-related peptide
      (ATRP), a neuropeptide from the neuroscience model organism Aplysia californica,
      may form multiple diastereomers in the Aplysia central nervous system. We
      determined that ATRP exists as a d-amino acid-containing peptide (d2-ATRP) and
      identified a specific G protein-coupled receptor as an ATRP receptor.
      Interestingly, unlike many previously reported DAACPs and their all-l-residue
      analogs, both l-ATRP and d2-ATRP were potent agonists of this receptor and active
      in electrophysiological experiments. Finally, d2-ATRP was much more stable than
      its all-l-residue counterpart in Aplysia plasma, suggesting that in the case of
      ATRP, the primary role of the l- to d-residue isomerization may be to protect
      this peptide from aminopeptidase activity in the extracellular space. Our results
      indicate that l- to d-residue isomerization can occur even in an all-l-residue
      peptide with a known biological activity and that in some cases, this PTM may
      help modulate peptide signal lifetime in the extracellular space rather than
      activity at the cognate receptor.

PMID- 30194285
TI  - Oxidative cyclization of N-methyl-dopa by a fungal flavoenzyme of the amine
      oxidase family.
AB  - Flavin-dependent enzymes catalyze many oxidations, including formation of ring
      structures in natural products. The gene cluster for biosynthesis of fumisoquins,
      secondary metabolites structurally related to isoquinolines, in the filamentous
      fungus Aspergillus fumigatus harbors a gene that encodes a flavoprotein of the
      amine oxidase family, termed fsqB (fumisoquin biosynthesis gene B). This enzyme
      catalyzes an oxidative ring closure reaction that leads to the formation of
      isoquinoline products. This reaction is reminiscent of the oxidative cyclization
      reported for berberine bridge enzyme and tetrahydrocannabinol synthase. Despite
      these similarities, amine oxidases and berberine bridge enzyme-like enzymes
      possess distinct structural properties, prompting us to investigate the structure
      function relationships of FsqB. Here, we report the recombinant production and
      purification of FsqB, elucidation of its crystal structure, and kinetic analysis
      employing five putative substrates. The crystal structure at 2.6 A resolution
      revealed that FsqB is a member of the amine oxidase family with a covalently
      bound FAD cofactor. N-methyl-dopa was the best substrate for FsqB and was
      completely converted to the cyclic isoquinoline product. The absence of the meta
      hydroxyl group, as e.g. in l-N-methyl-tyrosine, resulted in a 25-fold lower rate
      of reduction and the formation of the demethylated product l-tyrosine, instead of
      a cyclic product. Surprisingly, FsqB did not accept the d-stereoisomer of N
      methyltyrosine, in contrast to N-methyl-dopa, for which both stereoisomers were
      oxidized with similar rates. On the basis of the crystal structure and docking
      calculations, we postulate a substrate-dependent population of distinct binding
      modes that rationalizes stereospecific oxidation in the FsqB active site.

PMID- 30194286
TI  - Inhibition of JAK2/STAT3 Signaling Pathway Suppresses Proliferation of Burkitt's
      Lymphoma Raji Cells via Cell Cycle Progression, Apoptosis, and Oxidative Stress
      by Modulating HSP70.
AB  - BACKGROUND The aim of this study was to investigate the effect of the JAK2/STAT3
      pathway on the proliferation, cell cycle distribution, apoptosis, and oxidative
      stress of Raji cells via regulating HSP70 expression. MATERIAL AND METHODS Raji
      cells were divided into Blank, HSP70 siRNA, NC siRNA, AG490 (a JAK2/STAT3
      signaling pathway inhibitor), and HSP70 siRNA + rh JAK2 (recombinant human JAK2)
      groups. HSP70 expression was detected by quantitative real-time reverse
      transcription-PCR (qRT-PCR); the expression levels of HSP70 and JAK2/STAT3
      pathway-related proteins were evaluated by Western blotting; cell proliferation
      was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
      (MTT) assays; cell cycle distribution was observed by flow cytometry; cell
      apoptosis was tested by Annexin V-FITC/PI and Hoechst 33342/PI staining; reactive
      oxygen species (ROS) production was measured by dichloro-dihydro-fluorescein
      diacetate (DCFH-DA) assays; and MDA content and SOD and GSH-Px activities were
      determined using detection kits. RESULTS AG490 obviously down-regulated HSP70
      expression, inhibited proliferation, induced cell cycle arrest at the G0/G1
      phase, and promoted apoptosis in Raji cells; these effects were similar to the
      effects of HSP70 siRNA. Furthermore, ROS production and MDA content were
      increased in Raji cells treated with HSP70 siRNA or AG490, while SOD and GSH-Px
      activities were reduced. Raji cells in the HSP70 siRNA + rh JAK2 group did not
      significantly differ from those in the Blank group in regards to proliferation,
      cell cycle, apoptosis, and oxidative stress. CONCLUSIONS Blocking the JAK2/STAT3
      signaling pathway may inhibit proliferation, induce cell cycle arrest, and
      promote oxidative stress and apoptosis in Raji cells via the down-regulation of
      HSP70.

PMID- 30194288
TI  - Cortical substrates of cue-reactivity in multiple substance dependent
      populations: transdiagnostic relevance of the medial prefrontal cortex.
AB  - Elevated drug-cue elicited brain activity is one of the most widely cited,
      transdiagnostically relevant traits of substance dependent populations. These
      populations, however, are typically studied in isolation. The goal of this study
      was to prospectively investigate the spatial topography of drug-cue reactivity in
      a large set of individuals dependent on either cocaine, alcohol, or nicotine.
      Functional MRI data was acquired from 156 substance dependent individuals (55
      cocaine, 53 alcohol, and 48 nicotine) as they performed a standardized drug-cue
      exposure task. Clusters of significant activation to drug-cues relative to
      neutral cues ('hot spots') were isolated for each individual. K-means clustering
      was used to classify the spatial topography of the hotspots in the data set. The
      percentage of hotspots that would be reached at several distances (2-5 cm) of
      transcranial magnetic stimulation (TMS) were calculated. One hundred and three
      participants had at least one cluster of significant frontal cortex activity
      (66%). K-means revealed 3 distinct clusters within the medial prefrontal cortex
      (MPFC), left inferior frontal gyrus/insula, right premotor cortex. For the group
      as a whole (and for alcohol users and nicotine users independently), medial
      prefrontal cortex (BA 10) was the location of the greatest number of hotspots.
      The frontal pole was cortical location closest to the largest percentage of
      hotspots. While there is individual variability in the location of the cue
      elicited 'hot spot' these data demonstrate that elevated BOLD signal to drug cues
      in the MPFC may be a transdiagnostic endophenotype of addiction which may also be
      a fruitful neuromodulation target.

PMID- 30194287
TI  - Gut microbiota regulates mouse behaviors through glucocorticoid receptor pathway
      genes in the hippocampus.
AB  - Gut microbiota has an important role in the immune system, metabolism, and
      digestion, and has a significant effect on the nervous system. Recent studies
      have revealed that abnormal gut microbiota induces abnormal behaviors, which may
      be associated with the hypothalamic-pituitary-adrenal (HPA) axis. Therefore, we
      investigated the behavioral changes in germ-free (GF) mice by behavioral tests,
      quantified the basal serum cortisol levels, and examined glucocorticoid receptor
      pathway genes in hippocampus using microarray analysis followed by real-time PCR
      validation, to explore the molecular mechanisms by which the gut microbiota
      influences the host's behaviors and brain function. Moreover, we quantified the
      basal serum cortisol levels and validated the differential genes in an
      Escherichia coli-derived lipopolysaccharide (LPS) treatment mouse model and fecal
      "depression microbiota" transplantation mouse model by real-time PCR. We found
      that GF mice showed antianxiety- and antidepressant-like behaviors, whereas E.
      coli LPS-treated mice showed antidepressant-like behavior, but did not show
      antianxiety-like behavior. However, "depression microbiota" recipient mice
      exhibited anxiety- and depressive-like behaviors. In addition, six glucocorticoid
      receptor pathway genes (Slc22a5, Aqp1, Stat5a, Ampd3, Plekhf1, and Cyb561) were
      upregulated in GF mice, and of these only two (Stat5a and Ampd3) were upregulated
      in LPS-treated mice, whereas the shared gene, Stat5a, was downregulated in
      "depression microbiota" recipient mice. Furthermore, basal serum cortisol levels
      were decreased in E. coli LPS-treated mice but not in GF mice and "depression
      microbiota" recipient mice. These results indicated that the gut microbiota may
      lead to behavioral abnormalities in mice through the downstream pathway of the
      glucocorticoid receptor. Herein, we proposed a new insight into the molecular
      mechanisms by which gut microbiota influence depressive-like behavior.

PMID- 30194289
TI  - The role of acid-sensitive ion channels in panic disorder: a systematic review of
      animal studies and meta-analysis of human studies.
AB  - Acid-sensitive ion channels, such as amiloride-sensitive cation channel (ACCN),
      transient receptor potential vanilloid-1 (TRPV1), and T-cell death-associated
      gene 8 (TDAG8) are highly related to the expression of fear and are expressed in
      several regions of the brain. These molecules can detect acidosis and maintain
      brain homeostasis. An important role of pH homeostasis has been suggested in the
      physiology of panic disorder (PD), with acidosis as an interoceptive trigger for
      panic attacks. To examine the effect of acid-sensitive channels on PD symptoms,
      we conducted a systematic review and meta-analysis of these chemosensors in
      rodents and humans. Following PRISMA guidelines, we systematically searched the
      Web of Science, Medline/Pubmed, Scopus, Science Direct, and SciELO databases. The
      review included original research in PD patients and animal models of PD that
      investigated acid-sensitive channels and PD symptoms. Studies without a control
      group, studies involving patients with a comorbid psychiatric diagnosis, and in
      vitro studies were excluded. Eleven articles met the inclusion criteria for the
      systematic review. The majority of the studies showed an association between
      panic symptoms and acid-sensitive channels. PD patients appear to display
      polymorphisms in the ACCN gene and elevated levels of TDAG8 mRNA. The results
      showed a decrease in panic-like symptoms after acid channel blockade in animal
      models. Despite the relatively limited data on this topic in the literature, our
      review identified evidence linking acid-sensitive channels to PD in humans and
      preclinical models. Future research should explore possible underlying mechanisms
      of this association, attempt to replicate the existing findings in larger
      populations, and develop new therapeutic strategies based on these biological
      features.

PMID- 30194291
TI  - Facultative dosage compensation of developmental genes on autosomes in Drosophila
      and mouse embryonic stem cells.
AB  - Haploinsufficiency and aneuploidy are two phenomena, where gene dosage
      alterations cause severe defects ultimately resulting in developmental failures
      and disease. One remarkable exception is the X chromosome, where copy number
      differences between sexes are buffered by dosage compensation systems. In
      Drosophila, the Male-Specific Lethal complex (MSLc) mediates upregulation of the
      single male X chromosome. The evolutionary origin and conservation of this
      process orchestrated by MSL2, the only male-specific protein within the fly MSLc,
      have remained unclear. Here, we report that MSL2, in addition to regulating the X
      chromosome, targets autosomal genes involved in patterning and morphogenesis.
      Precise regulation of these genes by MSL2 is required for proper development.
      This set of dosage-sensitive genes maintains such regulation during evolution, as
      MSL2 binds and similarly regulates mouse orthologues via Histone H4 lysine 16
      acetylation. We propose that this gene-by-gene dosage compensation mechanism was
      co-opted during evolution for chromosome-wide regulation of the Drosophila male
      X.

PMID- 30194292
TI  - Passive sensing around the corner using spatial coherence.
AB  - When direct vision is obstructed, detecting an object usually involves either
      using mirrors or actively controlling some of the properties of light used for
      illumination. In our paradigm, we show that a highly scattering wall can transfer
      certain statistical properties of light, which, in turn, can assist in detecting
      objects even in non-line-of-sight conditions. We experimentally demonstrate that
      the transformation of spatial coherence during the reflection of light from a
      diffusing wall can be used to retrieve geometric information about objects hidden
      around a corner and assess their location. This sensing approach is completely
      passive, assumes no control over the source of light, and relies solely on
      natural broadband illumination.

PMID- 30194290
TI  - Interrogating the protein interactomes of RAS isoforms identifies PIP5K1A as a
      KRAS-specific vulnerability.
AB  - In human cancers, oncogenic mutations commonly occur in the RAS genes KRAS, NRAS,
      or HRAS, but there are no clinical RAS inhibitors. Mutations are more prevalent
      in KRAS, possibly suggesting a unique oncogenic activity mediated by KRAS
      specific interaction partners, which might be targeted. Here, we determine the
      specific protein interactomes of each RAS isoform by BirA proximity-dependent
      biotin identification. The combined interactomes are screened by CRISPR-Cas9 loss
      of-function assays for proteins required for oncogenic KRAS-dependent, NRAS
      dependent, or HRAS-dependent proliferation and censored for druggable proteins.
      Using this strategy, we identify phosphatidylinositol phosphate kinase PIP5K1A as
      a KRAS-specific interactor and show that PIP5K1A binds to a unique region in
      KRAS. Furthermore, PIP5K1A depletion specifically reduces oncogenic KRAS
      signaling and proliferation, and sensitizes pancreatic cancer cell lines to a
      MAPK inhibitor. These results suggest PIP5K1A as a potential target in KRAS
      signaling for the treatment of KRAS-mutant cancers.

PMID- 30194293
TI  - Modular engineering to increase intracellular NAD(H/+) promotes rate of
      extracellular electron transfer of Shewanella oneidensis.
AB  - The slow rate of extracellular electron transfer (EET) of electroactive
      microorganisms remains a primary bottleneck that restricts the practical
      applications of bioelectrochemical systems. Intracellular NAD(H/+) (i.e., the
      total level of NADH and NAD+) is a crucial source of the intracellular electron
      pool from which intracellular electrons are transferred to extracellular electron
      acceptors via EET pathways. However, how the total level of intracellular
      NAD(H/+) impacts the EET rate in Shewanella oneidensis has not been established.
      Here, we use a modular synthetic biology strategy to redirect metabolic flux
      towards NAD+ biosynthesis via three modules: de novo, salvage, and universal
      biosynthesis modules in S. oneidensis MR-1. The results demonstrate that an
      increase in intracellular NAD(H/+) results in the transfer of more electrons from
      the increased oxidation of the electron donor to the EET pathways of S.
      oneidensis, thereby enhancing intracellular electron flux and the EET rate.

PMID- 30194294
TI  - Refined efficacy estimates of the Sanofi Pasteur dengue vaccine CYD-TDV using
      machine learning.
AB  - CYD-TDV is the first licensed dengue vaccine for individuals 9-45 (or 60) years
      of age. Using 12% of the subjects enroled in phase-2b and phase-3 trials for
      which baseline serostatus was measured, the vaccine-induced protection against
      virologically confirmed dengue during active surveillance (0-25 months) was found
      to vary with prior exposure to dengue. Because age and dengue exposure are highly
      correlated in endemic settings, refined insight into how efficacy varies by
      serostatus and age is essential to understand the increased risk of
      hospitalisation observed among vaccinated individuals during the long-term follow
      up and to develop safe and effective vaccination strategies. Here we apply
      machine learning to impute the baseline serostatus for subjects with post-dose 3
      titres but missing baseline serostatus. We find evidence for age dependence in
      efficacy independent of serostatus and estimate that among 9-16 year olds, CYD
      TDV is protective against serotypes 1, 3 and 4 regardless of baseline serostatus.

PMID- 30194295
TI  - Focused clamping of a single neuronal SNARE complex by complexin under high
      mechanical tension.
AB  - Neuronal soluble N-ethylmaleimide-sensitive factor attachment protein receptors
      (SNAREs) catalyze synaptic vesicle fusion with presynaptic membranes through the
      formation of SNARE complexes. Complexin (Cpx) is the only presynaptic protein
      that tightly binds to SNAREs and regulates membrane fusion, but how it modulates
      the energy landscape of SNARE complex assembly, especially under mechanical
      tension on the complex, remains unclear. Here, using magnetic tweezers, we report
      how Cpx interacts with single SNARE complexes. The effects of Cpx manifest only
      under high mechanical tensions above 13 pN. Cpx stabilizes the central four-helix
      bundle of SNARE motifs and, at the same time, prevents the complete zippering of
      SNAREs by inhibiting linker-domain assembly. These results suggest that Cpx
      generates a focused clamp for the neuronal SNARE complex in a linker-open
      conformation. Our results provide a hint as to how Cpx cooperates with neuronal
      SNAREs to prime synaptic vesicles in preparation for synchronous neurotransmitter
      release.

PMID- 30194296
TI  - Staufen1 links RNA stress granules and autophagy in a model of neurodegeneration.
AB  - Spinocerebellar ataxia type 2 (SCA2) is a neurodegenerative disease caused by
      expansion of polyglutamine tract in the ATXN2 protein. We identified Staufen1
      (STAU1) as an interactor of ATXN2, and showed elevation in cells from SCA2
      patients, amyotrophic lateral sclerosis (ALS) patients, and in SCA2 mouse models.
      We demonstrated recruitment of STAU1 to mutant ATXN2 aggregates in brain tissue
      from patients with SCA2 human brain and in an SCA2 mouse model, and association
      of STAU1 elevation with dysregulation of SCA2-related transcript abundances.
      Targeting STAU1 in vitro by RNAi restored PCP2 transcript levels and lowering
      mutant ATXN2 also normalized STAU1 levels. Reduction of Stau1 in vivo improved
      motor behavior in an SCA2 mouse model, normalized the levels of several SCA2
      related proteins, and reduced aggregation of polyglutamine-expanded ATXN2. These
      findings suggest a function for STAU1 in aberrant RNA metabolism associated with
      ATXN2 mutation, suggesting STAU1 is a possible novel therapeutic target for SCA2.

PMID- 30194297
TI  - Highly efficient genome editing by CRISPR-Cpf1 using CRISPR RNA with a
      uridinylate-rich 3'-overhang.
AB  - Genome editing has been harnessed through the development of CRISPR system, and
      the CRISPR from Prevotella and Francisella 1 (Cpf1) system has emerged as a
      promising alternative to CRISPR-Cas9 for use in various circumstances. Despite
      the inherent multiple advantages of Cpf1 over Cas9, the adoption of Cpf1 has been
      unsatisfactory because of target-dependent insufficient indel efficiencies. Here,
      we report an engineered CRISPR RNA (crRNA) for highly efficient genome editing by
      Cpf1, which includes a 20-base target-complementary sequence and a uridinylate
      rich 3'-overhang. When the crRNA is transcriptionally produced, crRNA with a 20
      base target-complementary sequence plus a U4AU4 3'-overhang is the optimal
      configuration. U-rich crRNA also maximizes the utility of the AsCpf1 mutants and
      multiplexing genome editing using mRNA as the source of multiple crRNAs.
      Furthermore, U-rich crRNA enables a highly safe and specific genome editing using
      Cpf1 in human cells, contributing to the enhancement of a genome-editing toolbox.

PMID- 30194298
TI  - Author Correction: Revealing the mechanism for covalent inhibition of glycoside
      hydrolases by carbasugars at an atomic level.
AB  - In the originally published version of this Article, the affiliation details for
      Tracey M. Gloster were incorrectly given as 'Department of Molecular Biology and
      Biochemistry, Simon Fraser University, 8888 University Drive, Burnaby, BC V5A
      1S6, Canada'. The correct affiliation is 'Biomedical Sciences Research Complex,
      University of St Andrews, North Haugh, St Andrews, Fife, KY16 9ST, UK'. This has
      now been corrected in both the PDF and HTML versions of the Article.

PMID- 30194299
TI  - Stereoselective oxidative glycosylation of anomeric nucleophiles with alcohols
      and carboxylic acids.
AB  - Oligosaccharides, one of the most abundant biopolymers, are involved in numerous
      biological processes. Although many efforts have been put in preparative
      carbohydrate chemistry, achieving optimal anomeric and regioselectivities remains
      challenging. Herein we describe an oxidative glycosylation method between
      anomeric stannanes and oxygen nucleophiles resulting in the formation of a C-O
      bond with consistently high anomeric control for glycosyl donors bearing a free
      C2-hydroxyl group. These reactions are promoted by hypervalent iodine reagents
      with catalytic or stoichiometric amounts of Cu or Zn salts. The generality of
      this transformation is demonstrated in 42 examples. Mechanistic studies indicate
      that the oxidative glycosylation is initiated by the hydroxyl-guided delivery of
      the hypervalent iodine and tosylate into the anomeric position, and results in
      excellent 1,2-trans selectivity. The unique mechanistic paradigm, high
      selectivities, and mild reaction conditions make this method suitable for the
      synthesis of oligosaccharides and for integration with other methodologies such
      as automated synthesis.

PMID- 30194300
TI  - Correct determination of charge transfer state energy from luminescence spectra
      in organic solar cells.
AB  - Generation and recombination of electrons and holes in organic solar cells occurs
      via charge transfer states located at the donor/acceptor interface. The energy of
      these charge transfer states is a crucial factor for the attainable open-circuit
      voltage and its correct determination is thus of utmost importance for a detailed
      understanding of such devices. This work reports on drastic changes of
      electroluminescence spectra of bulk heterojunction organic solar cells upon
      variation of the absorber layer thickness. It is shown that optical thin-film
      effects have a large impact on optical out-coupling of luminescence radiation for
      devices made from different photoactive materials, in configurations with and
      without indium tin oxide. A scattering matrix approach is presented which
      accurately reproduces the observed effects and thus delivers the radiative
      recombination spectra corrected for the wavelength-dependent out-coupling. This
      approach is proven to enable the correct determination of charge transfer state
      energies.

PMID- 30194301
TI  - Conservation of epigenetic regulation by the MLL3/4 tumour suppressor in
      planarian pluripotent stem cells.
AB  - Currently, little is known about the evolution of epigenetic regulation in animal
      stem cells. Here we demonstrate, using the planarian stem cell system to
      investigate the role of the COMPASS family of MLL3/4 histone methyltransferases
      that their function as tumor suppressors in mammalian stem cells is conserved
      over a long evolutionary distance. To investigate the potential conservation of a
      genome-wide epigenetic regulatory program in animal stem cells, we assess the
      effects of Mll3/4 loss of function by performing RNA-seq and ChIP-seq on the G2/M
      planarian stem cell population, part of which contributes to the formation of
      outgrowths. We find many oncogenes and tumor suppressors among the affected genes
      that are likely candidates for mediating MLL3/4 tumor suppression function. Our
      work demonstrates conservation of an important epigenetic regulatory program in
      animals and highlights the utility of the planarian model system for studying
      epigenetic regulation.

PMID- 30194303
TI  - Manipulating and visualizing the dynamic aggregation-induced emission within a
      confined quartz nanopore.
AB  - Aggregation-induced emission (AIE) as a unique photophysical process has been
      intensively explored for their features in fields from optical sensing,
      bioimaging to optoelectronic devices. However, all AIE luminogens (AIEgens)
      hardly recover into the initial dispersed state after illuminating at the
      ultimate aggregated state, which limits AIEgens to achieve reversible sensing and
      reproducible devices. To real-time manipulate the emission of AIEgen, here we
      take the advantage of confined space in the quartz nanopore to achieve a nanopore
      size-dependent restriction of AIEgens for reversible conversions of "on-to-off"
      and "off-to-on" emission. By electrochemically manipulating 26 fL AIEgen solution
      inside nanopore confinement, AIE illuminates while moves along nanopore from the
      constricted tip to inside cavity at a velocity of 1.4-2.2 MUm s-1, and vice
      versa. We further apply this dynamic manipulation for a target delivery of AIEgen
      into single cells, which opens up new possibility to design powerful and
      practical AIE applications.

PMID- 30194302
TI  - Necroptosis mediates myofibre death in dystrophin-deficient mice.
AB  - Duchenne muscular dystrophy (DMD) is a severe degenerative disorder caused by
      mutations in the dystrophin gene. Dystrophin-deficient muscles are characterised
      by progressive myofibre necrosis in which inflammation plays a deleterious role.
      However, the molecular mechanisms underlying inflammation-induced necrosis in
      muscle cells are unknown. Here we show that necroptosis is a mechanism underlying
      myofibre death in dystrophin-deficient muscle. RIPK1, RIPK3 and MLKL are
      upregulated in dystrophic mouse myofibres. In human DMD samples, there is strong
      immunoreactivity to RIPK3 and phospho-MLKL in myofibres. In vitro, TNFalpha can
      elicit necroptosis in C2C12 myoblasts, and RIPK3 overexpression sensitises
      myoblasts to undergo TNF-induced death. Furthermore, genetic ablation of Ripk3 in
      mdx mice reduces myofibre degeneration, inflammatory infiltrate, and muscle
      fibrosis, and eventually improves muscle function. These findings provide the
      first evidence of necroptotic cell death in a disease affecting skeletal muscle
      and identify RIPK3 as a key player in the degenerative process in dystrophin
      deficient muscles.

PMID- 30194304
TI  - Boosting potassium-ion batteries by few-layered composite anodes prepared via
      solution-triggered one-step shear exfoliation.
AB  - Earth-abundant potassium is a promising alternative to lithium in rechargeable
      batteries, but a pivotal limitation of potassium-ion batteries is their
      relatively low capacity and poor cycling stability. Here, a high-performance
      potassium-ion battery is achieved by employing few-layered antimony
      sulfide/carbon sheet composite anode fabricated via one-step high-shear
      exfoliation in ethanol/water solvent. Antimony sulfide with few-layered structure
      minimizes the volume expansion during potassiation and shortens the ion transport
      pathways, thus enhancing the rate capability; while carbon sheets in the
      composite provide electrical conductivity and maintain the electrode cycling
      stability by trapping the inevitable by-product, elemental sulfur. Meanwhile, the
      effect of the exfoliation solvent on the fabrication of two-dimensional antimony
      sulfide/carbon is also investigated. It is found that water facilitates the
      exfoliation by lower diffusion barrier along the [010] direction of antimony
      sulfide, while ethanol in the solvent acts as the carbon source for in situ
      carbonization.

PMID- 30194305
TI  - Decisions are expedited through multiple neural adjustments spanning the
      sensorimotor hierarchy.
AB  - When decisions are made under speed pressure, "urgency" signals elevate neural
      activity toward action-triggering thresholds independent of the sensory evidence,
      thus incurring a cost to choice accuracy. While urgency signals have been
      observed in brain circuits involved in preparing actions, their influence at
      other levels of the sensorimotor pathway remains unknown. We used a novel
      contrast-comparison paradigm to simultaneously trace the dynamics of sensory
      evidence encoding, evidence accumulation, motor preparation, and muscle
      activation in humans. Results indicate speed pressure impacts multiple
      sensorimotor levels but in crucially distinct ways. Evidence-independent urgency
      was applied to cortical action-preparation signals and downstream muscle
      activation, but not directly to upstream levels. Instead, differential sensory
      evidence encoding was enhanced in a way that partially countered the negative
      impact of motor-level urgency on accuracy, and these opposing sensory-boost and
      motor-urgency effects had knock-on effects on the buildup and pre-response
      amplitude of a motor-independent representation of cumulative evidence.

PMID- 30194307
TI  - A rationally designed JAZ subtype-selective agonist of jasmonate perception.
AB  - The phytohormone 7-iso-(+)-jasmonoyl-L-isoleucine (JA-Ile) mediates plant defense
      responses against herbivore and pathogen attack, and thus increases plant
      resistance against foreign invaders. However, JA-Ile also causes growth
      inhibition; and therefore JA-Ile is not a practical chemical regulator of plant
      defense responses. Here, we describe the rational design and synthesis of a small
      molecule agonist that can upregulate defense-related gene expression and promote
      pathogen resistance at concentrations that do not cause growth inhibition in
      Arabidopsis. By stabilizing interactions between COI1 and JAZ9 and JAZ10 but no
      other JAZ isoforms, the agonist leads to formation of JA-Ile co-receptors that
      selectively activate the JAZ9-EIN3/EIL1-ORA59 signaling pathway. The design of a
      JA-Ile agonist with high selectivity for specific protein subtypes may help
      promote the development of chemical regulators that do not cause a tradeoff
      between growth and defense.

PMID- 30194306
TI  - Aberrant splicing and defective mRNA production induced by somatic spliceosome
      mutations in myelodysplasia.
AB  - Spliceosome mutations are frequently found in myelodysplasia. Splicing
      alterations induced by these mutations, their precise targets, and the effect at
      the transcript level have not been fully elucidated. Here we report
      transcriptomic analyses of 265 bone marrow samples from myelodysplasia patients,
      followed by a validation using CRISPR/Cas9-mediated gene editing and an
      assessment of nonsense-mediated decay susceptibility. Small but widespread
      reduction of intron-retaining isoforms is the most frequent splicing alteration
      in SF3B1-mutated samples. SF3B1 mutation is also associated with 3' splice site
      alterations, leading to the most pronounced reduction of canonical transcripts.
      Target genes include tumor suppressors and genes of mitochondrial iron metabolism
      or heme biosynthesis. Alternative exon usage is predominant in SRSF2- and U2AF1
      mutated samples. Usage of an EZH2 cryptic exon harboring a premature termination
      codon is increased in both SRSF2- and U2AF1-mutated samples. Our study reveals a
      landscape of splicing alterations and precise targets of various spliceosome
      mutations.

PMID- 30194308
TI  - Tropical peatland carbon storage linked to global latitudinal trends in peat
      recalcitrance.
AB  - Peatlands represent large terrestrial carbon banks. Given that most peat
      accumulates in boreal regions, where low temperatures and water saturation
      preserve organic matter, the existence of peat in (sub)tropical regions remains
      enigmatic. Here we examined peat and plant chemistry across a latitudinal
      transect from the Arctic to the tropics. Near-surface low-latitude peat has lower
      carbohydrate and greater aromatic content than near-surface high-latitude peat,
      creating a reduced oxidation state and resulting recalcitrance. This
      recalcitrance allows peat to persist in the (sub)tropics despite warm
      temperatures. Because we observed similar declines in carbohydrate content with
      depth in high-latitude peat, our data explain recent field-scale deep peat
      warming experiments in which catotelm (deeper) peat remained stable despite
      temperature increases up to 9  degrees C. We suggest that high-latitude deep peat
      reservoirs may be stabilized in the face of climate change by their ultimately
      lower carbohydrate and higher aromatic composition, similar to tropical peats.

PMID- 30194309
TI  - Robust increase of leaf size by Arabidopsis thaliana GRF3-like transcription
      factors under different growth conditions.
AB  - An increase in crop yield is essential to reassure food security to meet the
      accelerating global demand. Several genetic modifications can increase organ
      size, which in turn might boost crop yield. Still, only in a few cases their
      performance has been evaluated under stress conditions. MicroRNA miR396 repress
      the expression of GROWTH-REGULATING FACTOR (GRF) genes that codes for
      transcription factors that promote organ growth. Here, we show that both
      Arabidopsis thaliana At-GRF2 and At-GRF3 genes resistant to miR396 activity
      (rGRF2 and rGRF3) increased organ size, but only rGRF3 can produce this effect
      without causing morphological defects. Furthermore, introduction of At-rGRF3 in
      Brassica oleracea can increase organ size, and when At-rGRF3 homologs from
      soybean and rice are introduced in Arabidopsis, leaf size is also increased. This
      suggests that regulation of GRF3 activity by miR396 is important for organ growth
      in a broad range of species. Plants harboring rGRF3 have larger leaves also under
      drought stress, a condition that stimulates miR396 accumulation. These plants
      also showed an increase in the resistance to virulent bacteria, suggesting that
      the size increment promoted by rGRF3 occurs without an obvious cost on plant
      defenses. Our findings indicate that rGRF3 can increase plant organ size under
      both normal and stress conditions and is a valuable tool for biotechnological
      applications.

PMID- 30194310
TI  - Author Correction: Role of extrinsic mechanical force in the development of the
      RA-I tactile mechanoreceptor.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 30194311
TI  - Interplay of alpha/beta-Relaxation Dynamics and the Shape of Ionomer Building
      Blocks.
AB  - The relation between the alpha/beta relaxations and the shape of the building
      blocks of ionomer materials is a key factor for programming an important
      temperature-dependent property: the memory of shape. However, the morphology of
      ionomers is indirectly obtained via modeling of small angle X-ray scattering
      (SAXS) data owing to the hardly accessible image characterization of the
      nanometric building blocks - micelle-like cylindrical polymeric aggregates
      (radius ~2-6 nm and length >100 nm). Herein, broadband dielectric spectroscopy
      (BDS) measurements, free from electrode polarization effects, allowed identifying
      the time and temperature dependence of the polarization of different length
      scales of the ionomer matrix, and more importantly, by directly providing the
      aspect ratio of the radius and length of the polymeric aggregates for each
      desired temperature. This finding is essential for controlling the shape of
      ionomer based functional products under several stimuli conditions, thereby
      advancing remarkable applications, such as four dimensional (4D) printing.

PMID- 30194312
TI  - Author Correction: Optical Manipulation of nanoparticles by simultaneous electric
      and magnetic field enhancement within diabolo nanoantenna.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 30194313
TI  - Author Correction: CB1 receptor activation induces intracellular Ca2+
      mobilization and 2-arachidonoylglycerol release in rodent spinal cord astrocytes.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 30194314
TI  - The Role of Whole-Body Magnetic Resonance Imaging (WB-MRI) in Patients with
      Paroxysmal Nocturnal Hemoglobinuria (PNH).
AB  - In PNH thromboembolic events (TEs) represent the leading cause of morbidity and
      mortality. Between Dec 2013 and Jan 2016 37 PNH patients (pts) (23 PNH, 14
      AA/PNH; 51% (19/37) females; median age 44 years, median D-dimer levels 0.22
      mg/l) were examined with a whole-body magnetic resonance imaging (WB-MRI) scan at
      1.5 T to detect TEs. Pts were treated according to German PNH guidelines,
      including eculizumab therapy. 64% (24/37) of the pts had no documented TEs prior
      to observation. Two pts had suspected TEs in their clinical history. 29% of the
      pts (11/37) had a known history of venous thromboses (deep venous thrombosis
      (DVT) (5/11), portal venous thrombosis (PVT) (4/11), vena caval thrombosis (VCT)
      (2/11). A myocardial infarction was reported in one pt, and two had a cerebral
      venous sinus thrombosis (CVST) or a thalamic infarction. Six pts (16%) had at
      least two prior TEs. In pts with prior TEs no progression of the existing TEs was
      observed. In pts on eculizumab and prior TEs as well as treatment-naive pts
      silent bone and renal infarctions were detected. Furthermore, a clinically non
      critical arterial occlusion was identified. WB-MRI scans present a novel, non
      invasive method to assess the complete vascular status of PNH pts and allow the
      detection of previously undiagnosed vascular complications, affecting treatment
      indications and regimens.

PMID- 30194315
TI  - Pancreatic Exocrine Tissue Architecture and Integrity are Maintained by E
      cadherin During Postnatal Development.
AB  - Cadherin-mediated cell-cell adhesion plays an important role in organ development
      and changes in cadherin expression are often linked to morphogenetic and
      pathogenic events. Cadherins interact with other intracellular components to form
      adherens junctions (AJs) and provide mechanical attachments between adjacent
      cells. E-cadherin (Cdh1) represents an integral component of these intercellular
      junctions. To elucidate the function of E-cadherin in the developing pancreas, we
      generated and studied pancreas-specific Cdh1-knockout (Cdh1DeltaPan/DeltaPan)
      mice. Cdh1DeltaPan/DeltaPan mice exhibit normal body size at birth, but fail to
      gain weight and become hypoglycemic soon afterward. We found that E-cadherin is
      not required for the establishment of apical-basal polarity or pancreatic
      exocrine cell identity at birth. However, four days after birth, the pancreata of
      Cdh1DeltaPan/DeltaPan mutants display progressive deterioration of exocrine
      architecture and dysregulation of Wnt and YAP signaling. At this time point, the
      acinar cells of Cdh1DeltaPan/DeltaPan mutants begin to exhibit ductal phenotypes,
      suggesting acinar-to-ductal metaplasia (ADM) in the E-cadherin-deficient
      pancreas. Our findings demonstrate that E-cadherin plays an integral role in the
      maintenance of exocrine architecture and regulation of homeostatic signaling. The
      present study provides insights into the involvement of cadherin-mediated cell
      cell adhesion in pathogenic conditions such as pancreatitis or pancreatic cancer.

PMID- 30194316
TI  - X-ray Fluorescence Nanotomography of Single Bacteria with a Sub-15 nm Beam.
AB  - X-ray Fluorescence (XRF) microscopy is a growing approach for imaging the trace
      element concentration, distribution, and speciation in biological cells at the
      nanoscale. Moreover, three-dimensional nanotomography provides the added
      advantage of imaging subcellular structure and chemical identity in three
      dimensions without the need for staining or sectioning of cells. To date,
      technical challenges in X-ray optics, sample preparation, and detection
      sensitivity have limited the use of XRF nanotomography in this area. Here, XRF
      nanotomography was used to image the elemental distribution in individual E. coli
      bacterial cells using a sub-15 nm beam at the Hard X-ray Nanoprobe beamline (HXN,
      3-ID) at NSLS-II. These measurements were simultaneously combined with
      ptychography to image structural components of the cells. The cells were embedded
      in small (3-20 um) sodium chloride crystals, which provided a non-aqueous matrix
      to retain the three-dimensional structure of the E. coli while collecting data at
      room temperature. Results showed a generally uniform distribution of calcium in
      the cells, but an inhomogeneous zinc distribution, most notably with concentrated
      regions of zinc at the polar ends of the cells. This work demonstrates that
      simultaneous two-dimensional ptychography and XRF nanotomography can be performed
      with a sub-15 nm beam size on unfrozen biological cells to co-localize elemental
      distribution and nanostructure simultaneously.

PMID- 30194317
TI  - Sex differences in lipid metabolism are affected by presence of the gut
      microbiota.
AB  - Physiological processes are differentially regulated between men and women. Sex
      and gut microbiota have each been demonstrated to regulate host metabolism, but
      it is unclear whether both factors are interdependent. Here, we determined to
      what extent sex-specific differences in lipid metabolism are modulated via the
      gut microbiota. While male and female Conv mice showed predominantly differential
      expression in gene sets related to lipid metabolism, GF mice showed differences
      in gene sets linked to gut health and inflammatory responses. This suggests that
      presence of the gut microbiota is important in sex-specific regulation of lipid
      metabolism. Further, we explored the role of bile acids as mediators in the cross
      talk between the microbiome and host lipid metabolism. Females showed higher
      total and primary serum bile acids levels, independent of presence of microbiota.
      However, in presence of microbiota we observed higher secondary serum bile acid
      levels in females compared to males. Analysis of microbiota composition displayed
      sex-specific differences in Conv mice. Therefore, our data suggests that bile
      acids possibly play a role in the crosstalk between the microbiome and sex
      specific regulation of lipid metabolism. In conclusion, our data shows that
      presence of the gut microbiota contributes to sex differences in lipid
      metabolism.

PMID- 30194318
TI  - Mammillary body regulates state-dependent fear by alternating cortical
      oscillations.
AB  - State-dependent memory describes a phenomenon that memory will be efficiently
      retrieved only when the brain state during retrieval matches the state during
      encoding. While a variety of psychoactive drugs, such as ethanol, cocaine,
      morphine and NMDA receptor antagonists, are able to induce state-dependent
      memory, the biological hallmark of brain state and neural mechanism of its
      regulation are still unknown. In this study, we found that MK-801 enhanced delta
      oscillations in awake mice, representing a drug-induced brain state, in which
      fear memory could only be successfully retrieved when the same drug condition was
      presented. We identified a key nucleus, mammillary body (MB), which regulates the
      specific brain state associated with MK-801. Chemogenetic silencing of MB neurons
      enhanced cortical delta oscillations and generated state-dependent memory.
      Moreover, optogenetic reconstitution of delta oscillations alone facilitated
      retrieval of fear memory encoded under MK-801. Our results indicated that delta
      oscillations in awake animals defined a specific brain state, in which memory
      formed is inaccessible under the normal condition, shining light on the neural
      mechanism underlying the fluctuation of memory retrieval and the role of MB in
      memory encoding and recall.

PMID- 30194319
TI  - Accurate sound localization behavior in a gleaning bat, Antrozous pallidus.
AB  - Acute auditory processing in bats is typically associated with echolocation. A
      subset of bats, called gleaners, listens to prey-generated noise to hunt surface
      dwelling prey. Gleaners depend less on echolocation to hunt and, therefore,
      accurate localization of prey-generated noise is necessary for foraging success.
      Here we studied azimuth sound localization behavior in the pallid bat, a gleaning
      bat in which spatial encoding has been studied extensively. We tested pallid bats
      on a relatively difficult open loop task (single sound, duration <= 200 ms). The
      bats were trained to face the midline when stimulus was presented, and this was
      confirmed with video analysis. Bats localized broadband noise (5-30 kHz) from 1
      out of 11 speakers spaced evenly across the horizontal plane of the frontal sound
      field. Approach to the correct speaker was rewarded. Pallid bats show accurate
      localization near the midline with mean errors between 3-6 degrees . Remarkably,
      the accuracy does not decline significantly at peripheral locations with bats
      averaging  <~7 degrees  error upto 72 degrees  off midline. Manipulation of
      stimulus bandwidth shows that higher frequencies (20-30 kHz) are necessary for
      accurate localization. Comparative studies of gleaning bats will reveal
      convergent adaptations across auditory systems for non-echolocation-based
      behaviors in bats.

PMID- 30194320
TI  - Comparative transcriptome analysis to identify putative genes involved in thymol
      biosynthesis pathway in medicinal plant Trachyspermum ammi L.
AB  - Thymol, as a dietary monoterpene, is a phenol derivative of cymene, which is the
      major component of the essential oil of Trachyspermum ammi (L.). It shows
      multiple biological activities: antifungal, antibacterial, antivirus and anti
      inflammatory. T. ammi, commonly known as ajowan, belongs to Apiaceae and is an
      important medicinal seed spice. To identify the putative genes involved in thymol
      and other monoterpene biosynthesis, we provided transcriptomes of four
      inflorescence tissues of two ajowan ecotypes, containing different thymol yield.
      This study has detected the genes encoding enzymes for the go-between stages of
      the terpenoid biosynthesis pathways. A large number of unigenes, differentially
      expressed between four inflorescence tissues of two ajowan ecotypes, was revealed
      by a transcriptome analysis. Furthermore, differentially expressed unigenes
      encoding dehydrogenases, transcription factors, and cytochrome P450s, which might
      be associated with terpenoid diversity in T. ammi, were identified. The
      sequencing data obtained in this study formed a valuable repository of genetic
      information for an understanding of the formation of the main constituents of
      ajowan essential oil and functional analysis of thymol-specific genes.
      Comparative transcriptome analysis led to the development of new resources for a
      functional breeding of ajowan.

PMID- 30194321
TI  - Hydrological interactions between oases and water vapor transportation in the
      Tarim Basin, northwestern China.
AB  - The spatial evolution of the oasis cold-wet effects in Tarim Basin, northwestern
      China, are explored quantitatively by using the China Meteorological Forcing
      Dataset, with spatial and temporal resolution of 0.1 degree and 3 hours,
      respectively, and the hydrological interactions between the oases and water vapor
      transfer are discussed to uncover the influence of oases on regional
      precipitation. The results reveal that the annual precipitation exhibits an
      increasing trend from desert toward oasis at all four oases. However, the cold
      effect is not the dominating factor increasing precipitation, since the maximum
      increasing rate of precipitation is accompanied by the minimum decreasing rate of
      temperature. Indeed, water vapor transportation is more important than the cold
      effect. The maximum promotion of precipitation is observed in western basin,
      where the water vapor transfer follows the gradients of decreasing temperature
      and increasing humidity. Conversely, the minimum promotion in southwestern basin
      results from water vapor transportation following the temperature increasing.
      Therefore, the transfer of water vapor and its interactions with local surface
      conditions determine the precipitation in oasis areas. Understanding these
      processes is crucial to exploring the formation and spatial layout of oases,
      which is helpful for preventing desertification and protecting the fragile oasis
      ecosystem.

PMID- 30194322
TI  - Differential effects of dietary fibres on colonic barrier function in elderly
      individuals with gastrointestinal symptoms.
AB  - Gastrointestinal problems are common in elderly and often associated with
      psychological distress and increased levels of corticotrophin-releasing hormone,
      a hormone known to cause mast cell (MC) degranulation and perturbed intestinal
      barrier function. We investigated if dietary fibres (non-digestible
      polysaccharides [NPS]) could attenuate MC-induced colonic hyperpermeability in
      elderly with gastrointestinal (GI) symptoms. Colonic biopsies from elderly with
      diarrhoea and/or constipation (n = 18) and healthy controls (n = 19) were mounted
      in Ussing chambers and pre-stimulated with a yeast-derived beta (beta)-glucan
      (0.5 mg/ml) or wheat-derived arabinoxylan (0.1 mg/ml) before the addition of the
      MC-degranulator Compound (C) 48/80 (10 ng/ml). Permeability markers were compared
      pre and post exposure to C48/80 in both groups and revealed higher baseline
      permeability in elderly with GI symptoms. beta-glucan significantly attenuated
      C48/80-induced hyperpermeability in elderly with GI symptoms but not in healthy
      controls. Arabinoxylan reduced MC-induced paracellular and transcellular
      hyperpermeability across the colonic mucosa of healthy controls, but did only
      attenuate transcellular permeability in elderly with GI symptoms. Our novel
      findings indicate that NPS affect the intestinal barrier differently depending on
      the presence of GI symptoms and could be important in the treatment of moderate
      constipation and/or diarrhoea in elderly.

PMID- 30194323
TI  - Bushfire smoke is pro-inflammatory and suppresses macrophage phagocytic function.
AB  - Bushfires are increasing in frequency and severity worldwide. Bushfire smoke
      contains organic/inorganic compounds including aldehydes and acrolein. We
      described suppressive effects of tobacco smoke on the phagocytic capacity of
      airway macrophages, linked to secondary necrosis of uncleared apoptotic
      epithelial cells, persistence of non-typeable H. influenzae (NTHi), and
      inflammation. We hypothesised that bushfire smoke extract (BFSE) would similarly
      impair macrophage function. THP-1 or monocyte-derived macrophages (MDM) were
      exposed to 1-10% BFSE prepared from foliage of 5 common Australian native plants
      (genus Acacia or Eucalyptus), or 10% cigarette smoke extract (CSE). Phagocytic
      recognition receptors were measured by flow cytometry; pro-inflammatory cytokines
      and caspase 1 by immunofluorescence or cytometric bead array; viability by LDH
      assay; and capsase-3/PARP by western blot. BFSE significantly decreased
      phagocytosis of apoptotic cells or NTHi by both THP-1 macrophages and MDM vs air
      control, consistent with the effects of CSE. BFSE significantly decreased MDM
      expression of CD36, CD44, SR-A1, CD206 and TLR-2 and increased active IL-1beta,
      caspase-1 and secreted IL-8. BFSE dose-dependently decreased THP-1 macrophage
      viability (5-fold increase in LDH at 10%) and significantly increased active
      caspase-3. BFSE impairs macrophage function to a similar extent as CSE,
      highlighting the need for further research, especially in patients with pre
      existing lung disease.

PMID- 30194324
TI  - Coal with Carbon Capture and Sequestration is not as Land Use Efficient as Solar
      Photovoltaic Technology for Climate Neutral Electricity Production.
AB  - Avoiding climate destabilization caused by greenhouse gas (GHG) emissions,
      requires climate-neutral electricity sources. It has been proposed that the GHG
      emissions from coal-fired power plants can be offset by carbon capture and
      sequestration or bio-sequestration. However, solar photovoltaic (PV) technology
      has recently declined so far in costs it now offers both technical and economic
      potential to offset all of coal-fired electricity use. PV only emits GHGs during
      fabrication and not during use. To determine which technical solution to climate
      neutral electricity generation should be preferred, this study aggregates and
      synthesizes life cycle analysis studies for exergy, GHG emissions and land
      transformation for climate-neutral electricity. The results show that because of
      lower exergy efficiencies coal plants emit 13-18 times more GHG and transform 5
      13 times more land than PV. Optimal bio-sequestration of coal-fired GHG requires
      62% of U.S. arable land or 89% of all U.S land with average forest cover. Carbon
      capture and storage and enhanced oil recovery can improve coal performance, but
      for all cases the results clearly show that PV is a far more effective use of
      land. Overall, for the first time this study found climate-neutral photovoltaic
      farms are a preferred solution to climate-neutral coal fired electricity
      generation.

PMID- 30194325
TI  - Analysis By Deep Sequencing of Discontinued Neurotropic Yellow Fever Vaccine
      Strains.
AB  - Deep sequencing of live-attenuated viral vaccines has focused on vaccines in
      current use. Here we report characterization of a discontinued live yellow fever
      (YF) vaccine associated with severe adverse events. The French neurotropic
      vaccine (FNV) strain of YF virus was derived empirically in 1930 by 260 passages
      of wild-type French viscerotropic virus (FVV) in mouse brain. The vaccine was
      administered extensively in French-speaking Africa until discontinuation in 1982,
      due to high rates of post-vaccination encephalitis in children. Using rare
      archive strains of FNV, viral RNAs were sequenced and analyzed by massively
      parallel, in silico methods. Diversity and specific population structures were
      compared in reference to the wild-type parental strain FVV, and between the
      vaccine strains themselves. Lower abundance of polymorphism content was observed
      for FNV strains relative to FVV. Although the vaccines were of lower diversity
      than FVV, heterogeneity between the vaccines was observed. Reversion to wild-type
      identity was variably observed in the FNV strains. Specific population structures
      were recovered from vaccines with neurotropic properties; loss of neurotropism in
      mice was associated with abundance of wild-type RNA populations. The analysis
      provides novel sequence evidence that FNV is genetically unstable, and that
      adaptation of FNV contributed to the neurotropic adverse phenotype.

PMID- 30194326
TI  - Characterizing thermal-oxidation behaviors of nuclear graphite by combining O2
      supply and micro surface area of graphite.
AB  - The effects of different parameters on oxidation rate are non-linear, interactive
      and diversified in which the change of adequacy of O2 supply is an important
      indicator. The influence of microstructure on oxidation rate became stronger
      worsening the fitting linearity to calculate the activation energy based on
      present method with the decreased adequacy of O2 supply due to the increase of
      temperature, the decrease of gas flow rate, etc. Here, we proposed a method to
      characterize thermal-oxidation behaviors of nuclear graphite by combining O2
      supply and micro surface area of graphite. The proposed method improved the
      linearity and reduced the standard error of Arrhenius plots of oxidized graphite
      IG-110 (10 L/min reactant gas) and ET-10 (0.2 L/min reactant gas). The value of
      activation energy of graphite IG-110 oxidized under ASTM D7542 condition is
      calculated as 220 kJ/mol by this method echoing the results of previous studies
      with sufficient O2 supply. For the conditions with less O2 supply at low gas flow
      rate and/or high temperature, the change of microstructure of oxidized graphite
      should be obtained as an important factor influencing oxidation rate of graphite.

PMID- 30194327
TI  - Human adenovirus type 17 from species D transduces endothelial cells and human
      CD46 is involved in cell entry.
AB  - More than 70 human adenoviruses with type-dependent pathogenicity have been
      identified but biological information about the majority of these virus types is
      scarce. Here we employed multiple sequence alignments and structural information
      to predict receptor usage for the development of an adenoviral vector with novel
      biological features. We report the generation of a cloned adenovirus based on
      human adenovirus type 17 (HAdV17) with high sequence homology to the well
      characterized human adenovirus type 37 (HAdV37) that causes epidemic
      keratoconjunctivitis (EKC). Our study revealed that human CD46 (CD46) is involved
      in cell entry of HAdV17. Moreover, we found that HAdV17 infects endothelial cells
      (EC) in vitro including primary cells at higher efficiencies compared to the
      commonly used human adenovirus type 5 (HAdV5). Using a human CD46 transgenic
      mouse model, we observed that HAdV17 displays a broad tropism in vivo after
      systemic injection and that it transduces ECs in this mouse model. We conclude
      that the HAdV17-based vector may provide a novel platform for gene therapy.

PMID- 30194328
TI  - Warming in the Agulhas Region during the Global Surface Warming Acceleration and
      Slowdown.
AB  - The Agulhas Region gains more heat during the global surface warming slowdown
      than acceleration period. Yet, mechanisms that cause excessive heat accumulation
      in this region remain largely unknown. We investigate the underlying physical
      processes and examine their influence on ocean heat changes in the last three
      decades. Heave is found to drive the increasing ocean heat content in the last
      three decades whereas elevated heat accumulation rate in slowdown compared than
      acceleration period is mainly attributed to spice. During the acceleration
      period, pure heaving of Subtropical Mode Water induced by wind stress change and
      pure warming caused by heat flux, leading to a strong heave component and
      relatively weak spice, drive the increases in ocean heat content. During the
      slowdown period, increasing salinity strengthens the spice, resulting in a higher
      heat accumulation rate compared to the acceleration period.

PMID- 30194329
TI  - Characterisation and functional predictions of canine long non-coding RNAs.
AB  - Long non-coding RNAs (lncRNAs) are a family of heterogeneous RNAs that play major
      roles in multiple biological processes. We recently identified an extended
      repertoire of more than 10,000 lncRNAs of the domestic dog however, predicting
      their biological functionality remains challenging. In this study, we have
      characterised the expression profiles of 10,444 canine lncRNAs in 26 distinct
      tissue types, representing various anatomical systems. We showed that lncRNA
      expressions are mainly clustered by tissue type and we highlighted that 44% of
      canine lncRNAs are expressed in a tissue-specific manner. We further demonstrated
      that tissue-specificity correlates with specific families of canine transposable
      elements. In addition, we identified more than 900 conserved dog-human lncRNAs
      for which we show their overall reproducible expression patterns between dog and
      human through comparative transcriptomics. Finally, co-expression analyses of
      lncRNA and neighbouring protein-coding genes identified more than 3,400 canine
      lncRNAs, suggesting that functional roles of these lncRNAs act as regulatory
      elements. Altogether, this genomic and transcriptomic integrative study of
      lncRNAs constitutes a major resource to investigate genotype to phenotype
      relationships and biomedical research in the dog species.

PMID- 30194330
TI  - Clinical evaluation of rapid fluorescent diagnostic immunochromatographic test
      for influenza A virus (H1N1).
AB  - Rapid diagnostic tests (RDTs) have been developed to detect influenza A virus for
      the swift diagnosis and management of patients. However, despite the simplicity
      and convenience, the low sensitivity of RDTs remains a limitation for their use
      in point of care testing (POCT). In this study, we developed a rapid fluorescent
      immunochromatographic strip test (FICT) and the performance of FICT was confirmed
      by the real-time reverse transcription-polymerase chain reaction (rRT-PCR) of
      H1N1, compared with that of RDT. The limit of detection (LOD) of FICT was
      improved by 16-fold compared to RDT. FICT showed 85.29% sensitivity (29/34) (95%
      Confidence Interval [95% CI]: 68.94 to 95.05), 100% specificity (26/26) (95% CI:
      86.78 to 100.00), and a strong correlation (kappa; 0. 92) compared with rRT-PCR
      (20 <= Ct <= 36). In contrast, RDT (Standard Diagnostics [SD] BIOLINE Influenza
      Ag A/ B/ A(H1N1) Pandemic) showed 55.88% sensitivity (19/34) (95% CI: 37.87 to
      72.82), 100% specificity (26/26) (95% CI: 77.07 to 100), and had a fair
      correlation with rRT-PCR (kappa; 0. 75). FICT had better sensitivity than RDT (P
      < 0.01; McNemar's test). Therefore, FICT has the potential to improve the quality
      of current rapid POCT for the diagnosis of influenza A/H1N1 infection.

PMID- 30194331
TI  - Height at three months can indicate overweight at two years in catch-up growth of
      small for gestational age infants.
AB  - This study aimed to find an indicator at three months to predict overweight and
      short stature at two years in small for gestational age (SGA) infants. A total of
      468 SGA infants and 4642 appropriate for gestational age (AGA) infants were
      included. Weight and height were measured at birth, three months and two years.
      Logistic regression and receiver operating characteristic (ROC) curves were
      performed for the catch-up growth. As compared to AGA infants, the weight of SGA
      infants was lower and the length/height was shorter at birth, three months, and
      two years. The weight of the catch-up group was significantly greater at birth
      and two years. The length/height of the catch-up group was greater at three
      months and two years. Trajectories of weight standard deviation score (SDS) and
      height SDS showed that the overweight group (BMI over the 85th percentile) had a
      shorter length/height SDS but a higher rate of the change in weight SDS during
      catch-up growth. The multivariate logistic regression indicated that that height
      at three months was an independent factor for prediction of catch-up growth at
      two years. The area under curve (AUC) was 0.801 with the 95% confidence interval
      (CI) from 0.726 to 0.876. Therefore, height at three months can predict
      overweight at two years.

PMID- 30194333
TI  - Zn Vacancy Formation Energy and Diffusion Coefficient of CVT ZnO Crystals in the
      Sub-Surface Micron Region.
AB  - By using positron annihilation spectroscopy methods, we have experimentally
      demonstrated the creation of isolated zinc vacancy concentrations >1020 cm-3 in
      chemical vapor transport (CVT)-grown ZnO bulk single crystals. X-ray diffraction
      omega-rocking curve (XRC) shows the good quality of ZnO single crystal with (110)
      orientation. The depth analysis of Auger electron spectroscopy indicates the
      atomic concentrations of Zn and O are almost stoichiometric and constant
      throughout the measurement. Boltzmann statistics are applied to calculate the
      zinc vacancy formation energies (Ef) of ~1.3-1.52 eV in the sub-surface micron
      region. We have also applied Fick's 2nd law to calculate the zinc diffusion
      coefficient to be ~1.07 * 10-14 cm2/s at 1100  degrees C. The zinc vacancies
      began annealing out at 300  degrees C and, by heating in the air, were completely
      annealed out at 700  degrees C.

PMID- 30194332
TI  - Establishment of keratinocyte cell lines from human hair follicles.
AB  - The advent of organotypic skin models advanced the understanding of complex
      mechanisms of keratinocyte differentiation. However, these models are limited by
      both availability of primary keratinocytes and donor variability. Keratinocytes
      derived from cultured hair follicles and interfollicular epidermis were
      immortalized by ectopic expression of SV40 and hTERT. The generated keratinocyte
      cell lines differentiated into stratified epidermis with well-defined stratum
      granulosum and stratum corneum in organotypic human skin models. They behaved
      comparable to primary keratinocytes regarding the expression of differentiation
      associated proteins, cell junction components and proteins associated with
      cornification and formed a barrier against biotin diffusion. Mechanistically, we
      found that SV40 large T-antigen expression, accompanied by a strong p53
      accumulation, was only detectable in the basal layer of the in vitro
      reconstructed epidermis. Inhibition of DNA-methylation resulted in expression of
      SV40 large T-antigen also in the suprabasal epidermal layers and led to
      incomplete differentiation of keratinocyte cell lines. Our study demonstrates the
      generation of keratinocyte cell lines which are able to fully differentiate in an
      organotypic skin model. Since hair follicles, as source for keratinocytes, can be
      obtained by minimally invasive procedures, our approach enables the generation of
      cell lines also from individuals not available for skin biopsies.

PMID- 30194334
TI  - Selective Deletion of Heparan Sulfotransferase Enzyme, Ndst1, in Donor
      Endothelial and Myeloid Precursor Cells Significantly Decreases Acute Allograft
      Rejection.
AB  - Early damage to transplanted organs initiates excess inflammation that can cause
      ongoing injury, a leading cause for late graft loss. The endothelial glycocalyx
      modulates immune reactions and chemokine-mediated haptotaxis, potentially driving
      graft loss. In prior work, conditional deficiency of the glycocalyx-modifying
      enzyme N-deacetylase-N-sulfotransferase-1 (Ndst1f/f TekCre+) reduced aortic
      allograft inflammation. Here we investigated modification of heparan sulfate (HS)
      and chemokine interactions in whole-organ renal allografts. Conditional donor
      allograft Ndst1 deficiency (Ndst1-/-; C57Bl/6 background) was compared to
      systemic treatment with M-T7, a broad-spectrum chemokine-glycosaminoglycan (GAG)
      inhibitor. Early rejection was significantly reduced in Ndst1-/- kidneys
      engrafted into wildtype BALB/c mice (Ndst1+/+) and comparable to M-T7 treatment
      in C57Bl/6 allografts (P < 0.0081). M-T7 lost activity in Ndst1-/- allografts,
      while M-T7 point mutants with modified GAG-chemokine binding displayed a range of
      anti-rejection activity. CD3+ T cells (P < 0.0001), HS (P < 0.005) and CXC
      chemokine staining (P < 0.012), gene expression in NFkappaB and JAK/STAT
      pathways, and HS and CS disaccharide content were significantly altered with
      reduced rejection. Transplant of donor allografts with conditional Ndst1
      deficiency exhibit significantly reduced acute rejection, comparable to systemic
      chemokine-GAG inhibition. Modified disaccharides in engrafted organs correlate
      with reduced rejection. Altered disaccharides in engrafted organs provide markers
      for rejection with potential to guide new therapeutic approaches in allograft
      rejection.

PMID- 30194335
TI  - Multi-scale interplays of biotic and abiotic drivers shape mammalian sub
      continental diversity over millions of years.
AB  - The reconstruction of deep-time diversity trends is key to understanding current
      and future species richness. Studies that statistically evaluate potential
      factors affecting paleodiversity have focused on continental and global, clade
      wide datasets, and thus we ignore how community species richness build-up to
      generate large-scale patterns over geological timescales. If community diversity
      is shaped by biotic interactions and continental and global diversities are
      governed by abiotic events, which are the modulators of diversity in
      subcontinental regions? To address this question, we model Iberian mammalian
      species richness over 13 million years (15 to 2 Ma) using exhaustive fossil
      evidence for subcontinental species' ecomorphology, environmental context, and
      biogeographic affinities, and quantitatively evaluate their impact on species
      richness. We find that the diversity of large Iberian mammals has been limited
      over time, with species richness showing marked fluctuations, undergoing
      substantial depletions as diversity surpasses a critical limit where a
      significant part of the niches is unviable. The strength of such diversity
      dependence has also shifted. Large faunal dispersals and environmental
      heterogeneity increased the system's critical diversity limit. Diversity growth
      rate (net migration and diversification) also oscillated, mainly modulated by
      functional saturation, patchiness of canopy cover, and local temperature and
      aridity. Our study provides quantitative support for subcontinental species pools
      being complex and dynamic systems where diversity is perpetually imbalanced over
      geological timescales. Subcontinental diversity-dependence dynamics are mainly
      modulated by a multi-scale interplay of biotic and abiotic factors, with abiotic
      factors playing a more relevant role.

PMID- 30194337
TI  - Optically-active metastable defects in volumetric nanoplasmonic composites.
AB  - Metastable defects in semiconductor materials have been well known for decades,
      but have only recently started to attract attention for their potential
      applications in information technology. Here, we describe active and passive
      nanoplasmonic materials with optically active metastable defects that can be
      switched on or off by cooling with or without laser illumination, respectively.
      To the best of our knowledge, this is the first report of metastable defects in
      either passive or active nanoplasmonic materials, and, more generally, in non
      semiconducting materials. The nanocomposites are made of a sodium-boron-phosphate
      glass matrix doped with silver nanoparticles (nAg) or co-doped with nAg and Er3+
      ions by NanoParticle Direct Doping method. We further show that the different
      origins of the two types of defect-related luminescence behaviour are
      attributable to either a metal-glass defect (MG1) or a metal-glass-rare-earth ion
      defect (MGR1). Such materials could potentially be used for data writing and
      erasing using laser illumination with a 'tight' focus such as direct laser
      writing.

PMID- 30194336
TI  - Early postoperative controlling nutritional status (CONUT) score is associated
      with complication III-V after hepatectomy in hepatocellular carcinoma: A
      retrospective cohort study of 1,334 patients.
AB  - Postoperative complication III-V is closely related with hepatectomy-related
      mortality for hepatocellular carcinoma (HCC) patients. The aim of the study was
      to investigate the relationship between CONUTS and postoperative complication III
      V. 1334 HCC patients who underwent hepatectomy were divided into two groups: high
      CONUTS group (early postoperative CONUTS >= 8, n = 659) and low CONUTS group
      (early postoperative CONUTS < 8, n = 675). The characteristics and clinical
      outcomes were compared and analyzed. Risk factors for postoperative complication
      III-V were evaluated by univariate and multivariate analysis. early postoperative
      CONUTS showed a good prediction ability for postoperative complication III-V
      (AUROC = 0.653, P < 0.001), with the cut-off value of 8. The high CONUTS group
      had higher incidence of postoperative pulmonary complications (12.0% vs 7.9%, P =
      0.011), bile leakage (2.6% vs 0.9%, P = 0.018), intra-abdominal hemorrhage (4.9%
      vs 1.6%, P = 0.001), postoperative liver failure Grade C (3.6% vs 1.0%, P =
      0.002), complication III-V (15.6% vs 6.2%, P < 0.001), length of ICU stay > 48
      hours (9.4% vs 4.1%, P < 0.001) and mortality in 90 days (2.6% vs 0.4%, P =
      0.001), longer period of postoperative hospitalization (10 (8-13) vs 9 (7-11)
      days, P < 0.001). Multivariable analysis revealed that early postoperative CONUTS
      >= 8 (OR = 2.054, 95%CI = 1.371-3.078, P < 0.001) was independently associated
      with postoperative complication III-V. Early postoperative CONUTS >= 8 was
      identified as a novel risk factor for postoperative complication III-V, and
      should be further evaluated as a predictive marker for who are to undergo liver
      resection.

PMID- 30194338
TI  - Single-shot memory-effect video.
AB  - Imaging through opaque scattering media is critically important in applications
      ranging from biological and astronomical imaging to metrology and security. While
      the random process of scattering in turbid media produces scattered light that
      appears uninformative to the human eye, a wealth of information is contained in
      the signal and can be recovered using computational post-processing techniques.
      Recent studies have shown that statistical correlations present in the scattered
      light, known as 'memory effects', allow for diffraction-limited imaging through
      opaque media without detailed knowledge of (or access to) the source or
      scatterer. However, previous methods require that the object and/or scatterer be
      static during the measurement. We overcome this limitation by combining
      traditional memory effect imaging with coded-aperture-based computational imaging
      techniques, which enables us to realize for the first time single-shot video of
      arbitrary dynamic scenes through dynamic, opaque media. This has important
      implications for a wide range of real-world imaging scenarios.

PMID- 30194339
TI  - Degradation of tetrabromobisphenol A in a paddy soil during sequential anoxic
      oxic incubation: Kinetics, metabolites, and potential pathways.
AB  - Due to the increasing pollution of tetrabromobisphenol A (TBBPA) in paddy soils,
      it is of great importance to explore the degradation of TBBPA under repeated
      anoxic-oxic conditions. In the present study, the degradation of TBBPA (kinetics,
      metabolites and potential pathways) and the influence of low molecular weight
      organic acid i.e., lactic acid were investigated in a paddy soil during
      sequential anoxic-oxic incubations. Under the anoxic condition, TBBPA in the non
      sterile soils was efficiently debrominated into three intermediates (including
      tri-BBPA, di-BBPA and mono-BBPA) and bisphenol A (BPA) with a rate constant (k)
      of 0.0371 d-1 and a half-life (t1/2) of 60.8 d. The debromination end product
      (BPA) steadily accumulated. Next, turning to the oxic conditions, the
      anaerobically accumulated BPA degraded rapidly, while the intermediates and TBBPA
      were desorbed from the bound residues and were persistent. The detection of tri
      BBPA followed by di-BBPA and mono-BBPA thereafter indicated that the
      dehalogenation of TBBPA was likely a stepwise removal of bromine atoms. A pathway
      of TBBPA -> tri-BBPA -> di-BBPA -> mono-BBPA -> BPA was thus proposed for TBBPA
      degradation. The degradation of TBBPA and its metabolites was biologically
      mediated. Moreover, the biodegradation of TBBPA could be significantly
      accelerated by the addition of lactic acid as an exogenous carbon source and
      electron donor, with k being increased to 0.0766 d-1 and t1/2 being shortened to
      31.9 d. The information will improve our understanding of biotic process
      associated with agronomic practices (such as applying organic fertilizers)
      contributing to TBBPA attenuation in the natural soil environment.

PMID- 30194340
TI  - Potential role of the HOXD8 transcription factor in cisplatin resistance and
      tumour metastasis in advanced epithelial ovarian cancer.
AB  - Few studies have examined the potential transcription factor (TF) simultaneously
      associated with cisplatin resistance and metastasis in ovarian cancer. To assess
      a related mechanism, a 345-channel protein/DNA array and transcriptional activity
      ELISA were performed to compare the TF activities in the cisplatin-sensitive
      SKOV3 and cisplatin-resistant SKOV3-DDP cells and in HO-8910 and the homologous
      highly metastatic HO-8910PM cells. In SKOV3-DDP vs. SKOV3 cells, 43 TFs were up
      regulated, while 31 were down-regulated. In HO-8910PM vs. HO-8910 cells, 13 TFs
      were up-regulated, while 18 were down-regulated. In these two models, 4 TFs
      (HOXD8(1), HOXD8(2), RB, RFX1/2/3) were simultaneously up-regulated, and 9 TFs
      (SRE, FKHR, Angiotensinogen ANG-IRE, Pax2, CD28RC/NF-IL2B, HLF, CPE, CBFB and c
      Ets-1) were down-regulated. HOXD8 mRNA and protein expression levels measured by
      reverse transcription polymerase chain reaction and ELISA, respectively, were
      significantly higher in SKOV3-DDP and HO-8910PM than in their corresponding cell
      lines (both p < 0.05). In 52 cases of different ovarian disease, the patients
      with recurrent and cisplatin-resistant ovarian cancer had higher expression
      levels of HOXD8 than patients with primary malignant tumours (p = 0.018, p =
      0.001) or benign tumours (p = 0.001, p < 0.001). Taken together, these results
      suggest that HOXD8 is potentially associated with both cisplatin resistance and
      metastasis in advanced ovarian cancer.

PMID- 30194341
TI  - Biosorption optimization, characterization, immobilization and application of
      Gelidium amansii biomass for complete Pb2+ removal from aqueous solutions.
AB  - Lead (Pb2+) is among the most toxic heavy metals even in low concentration and
      cause toxicity to human's health and other forms of life. It is released into the
      environment through different industrial activities. The biosorption of Pb2+ from
      aqueous solutions by biomass of commonly available, marine alga Gelidium amansii
      was studied. The effects of different variables on Pb2+ removal were estimated by
      a two-level Plackett-Burman factorial design to determine the most significant
      variables affecting Pb2+ removal % from aqueous solutions. Initial pH, Pb2+
      concentration and temperature were the most significant factors affecting Pb2+
      removal chosen for further optimization using rotatable central composite design.
      The maximum removal percentage (100%) of Pb2+ from aqueous solution by Gelidium
      amansii biomass was found under the optimum conditions: initial Pb2+
      concentration of 200 mg/L, temperature 45  degrees C, pH 4.5, Gelidium amansii
      biomass of 1 g/L and contact time of 60 minutes at static condition. FTIR
      analysis of algal biomass revealed the presence of carbonyl, methylene,
      phosphate, carbonate and phenolic groups, which are involved in the Pb2+ ions
      biosorption process. SEM analysis demonstrates the ability of Gelidium amansii
      biomass to adsorb and removes Pb2+ from aqueous solution. EDS analysis shows the
      additional optical absorption peak corresponding to the Pb2+ which confirms the
      involvement of Gelidium amansii biomass in the adsorption of Pb2+ ions from
      aqueous solution. Immobilized Gelidium amansii biomass was effective in Pb2+
      removal (100%) from aqueous solution at an initial concentration of 200 mg/L for
      3 h. In conclusion, it is demonstrated that the red marine alga Gelidium amansii
      biomass is a promising, efficient, ecofriendly, cost-effective and biodegradable
      biosorbent for the removal of Pb2+ from the environment and wastewater effluents.

PMID- 30194342
TI  - Preparation of nickel/PA12 composite particles by defect-induced electroless
      plating for use in SLS processing.
AB  - In this work, Ni particles/PA12 powders (Ni/PA12) and graphite oxide (GO)
      encapsulated Ni particles/PA12 powders (GO-Ni/PA12) composite powders were
      prepared by defect-included electroless plating technique, and its laser sintered
      behaviour was investigated. Results showed that a lot of defects could formed on
      the surface of CH3COOH etched PA12 powders. The defects would induce Ni and GO-Ni
      particles independently plated on the PA12 surface. Adding GO in the plating
      solution would facilitate the deposition of Ni particles, GO, and NiO on the PA
      12 surface, but inhibit the growth and the crystallinity of the Ni particles. The
      SLS process involved the contact of PA12 powders, the formation of sintering
      neck, the growth of sintering neck and the formation of fused solid. Sintering
      process could facilitate the re-arrangement of Ni particles due to surface
      tension and the growth of sintering neck. The Ni particles had well wettability,
      and the interfaces between Ni particles and PA 12 were contacted soundly. The
      tensile strength and bending strength of the 10 W-sintered Ni/PA12 specimen were
      50 MPa and 60 MPa. But SLS process caused the serious aggregation of GO-Ni
      particles due to higher concentration, activity and surface area of GO-Ni
      particles.

PMID- 30194343
TI  - The Arabidopsis RNA Polymerase II Carboxyl Terminal Domain (CTD) Phosphatase
      Like1 (CPL1) is a biotic stress susceptibility gene.
AB  - Crop breeding for improved disease resistance may be achieved through the
      manipulation of host susceptibility genes. Previously we identified multiple
      Arabidopsis mutants known as enhanced stress response1 (esr1) that have defects
      in a KH-domain RNA-binding protein and conferred increased resistance to the root
      fungal pathogen Fusarium oxysporum. Here, screening the same mutagenized
      population we discovered two further enhanced stress response mutants that also
      conferred enhanced resistance to F. oxysporum. These mutants also have enhanced
      resistance to a leaf fungal pathogen (Alternaria brassicicola) and an aphid pest
      (Myzus persicae), but not to the bacterial leaf pathogen Pseudomonas syringae.
      The causal alleles in these mutants were found to have defects in the ESR1
      interacting protein partner RNA Polymerase II Carboxyl Terminal Domain (CTD)
      Phosphatase-Like1 (CPL1) and subsequently given the allele symbols cpl1-7 and
      cpl1-8. These results define a new role for CPL1 as a pathogen and pest
      susceptibility gene. Global transcriptome analysis and oxidative stress assays
      showed these cpl1 mutants have increased tolerance to oxidative stress. In
      particular, components of biotic stress responsive pathways were enriched in cpl1
      over wild-type up-regulated gene expression datasets including genes related to
      defence, heat shock proteins and oxidative stress/redox state processes.

PMID- 30194345
TI  - Publisher Correction: Evolution of human malaria.
AB  - In the version of this News & Views originally published, the caption of Fig. 1
      failed to acknowledge that the figure was adapted from Fig. 1 of E. J. Scully, U.
      Kanjee & M. T. Duraisingh Curr. Opin. Microbiol. 40, 21-31; 2017. This omission
      failed to recognize the scholarly work of Erik J. Scully, Usheer Kanjee and Manoj
      T. Duraisingh in generating the original version of the figure. Figure 1 has now
      been replaced in the News & Views with a new figure and caption (see below)
      describing the status of genome sequencing for primate-infecting species in the
      Plasmodium genus, and the paper by Scully et al. has been cited in the caption
      and added to the reference list at number 12. The publisher and editors apologize
      to the authors of the original figure, the author of the News & Views, and our
      readers for this mistake.

PMID- 30194344
TI  - A global meta-analysis of yield stability in organic and conservation
      agriculture.
AB  - One of the primary challenges of our time is to enhance global food production
      and security. Most assessments in agricultural systems focus on plant yield. Yet,
      these analyses neglect temporal yield stability, or the variability and
      reliability of production across years. Here we perform a meta-analysis to assess
      temporal yield stability of three major cropping systems: organic agriculture and
      conservation agriculture (no-tillage) vs. conventional agriculture, comparing 193
      studies based on 2896 comparisons. Organic agriculture has, per unit yield, a
      significantly lower temporal stability (-15%) compared to conventional
      agriculture. Thus, although organic farming promotes biodiversity and is
      generally more environmentally friendly, future efforts should focus on reducing
      its yield variability. Our analysis further indicates that the use of green
      manure and enhanced fertilisation can reduce the yield stability gap between
      organic and conventional agriculture. The temporal stability (-3%) of no-tillage
      does not differ significantly from those of conventional tillage indicating that
      a transition to no-tillage does not affect yield stability.

PMID- 30194347
TI  - Rodent models for Alzheimer disease.
AB  - Animal models are indispensable tools for Alzheimer disease (AD) research. Over
      the course of more than two decades, an increasing number of complementary rodent
      models has been generated. These models have facilitated testing hypotheses about
      the aetiology and progression of AD, dissecting the associated pathomechanisms
      and validating therapeutic interventions, thereby providing guidance for the
      design of human clinical trials. However, the lack of success in translating
      rodent data into therapeutic outcomes may challenge the validity of the current
      models. This Review critically evaluates the genetic and non-genetic strategies
      used in AD modelling, discussing their strengths and limitations, as well as new
      opportunities for the development of better models for the disease.

PMID- 30194346
TI  - Matrin-3 is essential for fibroblast growth factor 2-dependent maintenance of
      neural stem cells.
AB  - To investigate the mechanisms underlying the maintenance of neural stem cells, we
      performed two-dimensional fluorescence-difference gel electrophoresis (2D-DIGE)
      targeting the nuclear phosphorylated proteins. Nuclear phosphorylated protein
      Matrin-3 was identified in neural stem cells (NSCs) after stimulation using
      fibroblast growth factor 2 (FGF2). Matrin-3 was expressed in the mouse embryonic
      subventricular and ventricular zones. Small interfering RNA (siRNA)-mediated
      knockdown of Matrin-3 caused neuronal differentiation of NSCs in vitro, and
      altered the cerebral layer structure of foetal brain in vivo. Transfection of
      Matrin-3 plasmids in which the serine 208 residue was point-mutated to alanine
      (Ser208Ala mutant Matrin3) and inhibition of Ataxia telangiectasia mutated kinase
      (ATM kinase), which phosphorylates Matrin-3 Ser208 residue, caused neuronal
      differentiation and decreased the proliferation of neurosphere-forming stem
      cells. Thus, our proteomic approach revealed that Matrin-3 phosphorylation was
      essential for FGF2-dependent maintenance of NSCs in vitro and in vivo.

PMID- 30194348
TI  - Liquid-state quantitative SERS analyzer on self-ordered metal liquid-like
      plasmonic arrays.
AB  - Liquid interfacial plasmonic platform is emerging for new sensors, catalysis, and
      tunable optical devices, but also promises an alternative for practical
      applications of surface-enhanced Raman spectroscopy (SERS). Here we show that
      vigorous mixing of chloroform with citrate-capped gold nanorod sols triggers the
      rapid self-assembly of three-dimensional plasmonic arrays at the chloroform/water
      (O/W) interface and produces a self-healing metal liquid-like brilliant golden
      droplet. The O phase itself generates stable SERS fingerprints and is a good
      homogeneous internal standard for quantitative analysis. This platform presents
      reversible O/W encasing in a common cuvette determined just by surface
      wettability of the container. Both O-in-W and W-in-O platforms exhibit excellent
      SERS sensitivity and reproducibility for different analytes by the use of a
      portable Raman device. It paves the way toward a practical and quantitative
      liquid-state SERS analyzer, likened to a simple UV-Vis spectrometer, that is far
      superior to typical solid substrate-based or nanoparticle sol-based analysis.

PMID- 30194349
TI  - Parallel fabrication of spiral surface structures by interference pattern of
      circularly polarized beams.
AB  - Mass migration of photo-isomeric azo-polymers occurs according to the light
      intensity gradient, and the morphological surface structure can be fabricated by
      the artificial distribution of light by applying the interference properties of
      coherent laser light. Recently, the optical radiation force has played an
      important role in the morphology for dielectric targets, and chiral structures
      have been fabricated according to the spirally gathering force distribution that
      arises due to the electric susceptibility. On the contrary, interference laser
      processing has been applied to process the surface or interior of the material,
      and nano- or micro-structures in the lattice have been fabricated in a single
      exposure to the interference pattern. The unit structures are mostly axisymmetric
      nanowhiskers, nanodrops and nanobumps, among others. In this experiment,
      interference laser processing of an azo-polymer dielectric target using a
      circularly polarised continuous-wave (CW) laser was examined, and a spiral
      structure was successfully fabricated. From the viewpoint of laser processing
      method, an optical spiral radiation force was introduced in interference laser
      processing for the first time.

PMID- 30194350
TI  - Random Genetic Drift and Selective Pressures Shaping the Blattabacterium Genome.
AB  - Estimates suggest that at least half of all extant insect genera harbor obligate
      bacterial mutualists. Whereas an endosymbiotic relationship imparts many benefits
      upon host and symbiont alike, the intracellular lifestyle has profound effects on
      the bacterial genome. The obligate endosymbiont genome is a product of opposing
      forces: genes important to host survival are maintained through physiological
      constraint, contrasted by the fixation of deleterious mutations and genome
      erosion through random genetic drift. The obligate cockroach endosymbiont,
      Blattabacterium - providing nutritional augmentation to its host in the form of
      amino acid synthesis - displays radical genome alterations when compared to its
      most recent free-living relative Flavobacterium. To date, eight Blattabacterium
      genomes have been published, affording an unparalleled opportunity to examine the
      direction and magnitude of selective forces acting upon this group of symbionts.
      Here, we find that the Blattabacterium genome is experiencing a 10-fold increase
      in selection rate compared to Flavobacteria. Additionally, the proportion of
      selection events is largely negative in direction, with only a handful of loci
      exhibiting signatures of positive selection. These findings suggest that the
      Blattabacterium genome will continue to erode, potentially resulting in an
      endosymbiont with an even further reduced genome, as seen in other insect groups
      such as Hemiptera.

PMID- 30194351
TI  - Preliminary report: parasympathetic tone links to functional brain networks
      during the anticipation and experience of visceral pain.
AB  - The mechanisms that underpin the anti-nociceptive effect of the parasympathetic
      nervous system (PNS) on visceral pain remain incompletely understood. We sought
      to describe the effect of resting parasympathetic tone on functional brain
      networks during the anticipation and experience of oesophageal pain. 21 healthy
      participants had their resting cardiac vagal tone (CVT), a validated measure of
      the PNS, quantified, and underwent functional magnetic resonance imaging during
      the anticipation and experience of painful oesophageal distention. The
      relationship between resting CVT and functional brain networks was examined using
      11 hypothesis-driven nodes and network-based statistics. A network comprising all
      nodes was apparent in individuals with high resting CVT, compared to those with
      low CVT, during oesophageal pain (family wise error rate (FWER)-corrected p <
      0.048). Functional connections included the thalamus-amygdala, thalamus
      hypothalamus, hypothalamus-nucleus accumbens, amygdala-pallidum, pallidum-nucleus
      accumbens and insula-pallidum. A smaller network was seen during pain
      anticipation, comprising the amygdala, pallidum and anterior insula (FWER
      corrected p < 0.049). These findings suggest that PNS tone is associated with
      functional brain networks during the anticipation and experience of visceral
      pain. Given the role of these subcortical regions in the descending inhibitory
      modulation of pain, these networks may represent a potential neurobiological
      explanation for the anti-nociceptive effect of the PNS.

PMID- 30194352
TI  - Subglacial discharge plume behaviour revealed by CTD-instrumented ringed seals.
AB  - Subglacial discharge plumes increase submarine melting of marine-terminating
      glaciers significantly; however, in-situ data on their properties and behaviour
      are limited. We present oceanographic data collected by ringed seals (Pusa
      hispida) instrumented with GPS-equipped conductivity-temperature-depth satellite
      relay data loggers (GPS-CTD-SRDLs) in Kongsfjorden, Svalbard, during 2012. The
      seals foraged just outside the plumes and collected hydrographic data from within
      the plumes' upwelling cores as they returned to the surface. The seals
      encountered water with fractions of subglacial discharge as high as 27% at 60 m
      below the ocean surface. The ringed seals responded rapidly to spatial and
      temporal variations in subglacial discharge at the glacier terminus, suggesting
      that prey becomes available quickly following the appearance of plumes. The
      seals' dive locations were used to monitor the presence of plumes over a four
      month period. High surface runoff from Kronebreen catchment created strong
      plumes, but weak plumes were present even during periods of low surface runoff.
      The continued retreat of Kronebreen, and other tidewater glaciers, will lead to
      the loss of these marine-termini as the glaciers retreat onto land. The
      techniques presented here improve our understanding of the drivers of glacial
      retreat and the implications of future habitat loss for glacier-associated birds
      and mammals.

PMID- 30194353
TI  - An original design of remote robot-assisted intubation system.
AB  - The success rate of pre-hospital endotracheal intubation (ETI) by paramedics is
      lower than physicians. We aimed to establish a remote robot-assisted intubation
      system (RRAIS) and expected it to improve success rate of pre-hospital ETI. To
      test the robot's feasibility, 20 pigs were intubated by direct laryngoscope or
      the robot system. Intubation time, success rate, airway complications were
      recorded during the experiment. The animal experiment showed that participants
      achieved a higher success rate in absolute numbers by the robot system. In
      summary, we have successfully developed a remote robot-assisted intubation
      system. It is promising for RRAIS to improve the success rate of pre-hospital ETI
      and change the current rescue model.

PMID- 30194355
TI  - Transcriptome analysis of differentially expressed unigenes involved in flavonoid
      biosynthesis during flower development of Chrysanthemum morifolium 'Chuju'.
AB  - Chrysanthemum morifolium is an ornamentally and medicinally important plant
      species. Up to date, molecular and genetic investigations have largely focused on
      determination of flowering time in the ornamental species. However, little is
      known about gene regulatory networks for the biosynthesis of flavonoids in the
      medicinal species. In the current study, we employed the high-throughput
      sequencing technology to profile the genome-wide transcriptome of C. morifolium
      'Chuju', a famous medicinal species in traditional Chinese medicine. A total of
      63,854 unigenes with an average length of 741 bp were obtained. Bioinformatic
      analysis has identified a great number of structural and regulatory unigenes
      potentially participating in the flavonoid biosynthetic pathway. According to the
      comparison of digital gene expression, 8,370 (3,026 up-regulated and 5,344 down
      regulated), 1,348 (717 up-regulated and 631 down-regulated) and 944 (206 up
      regulated and 738 down-regulated) differentially expressed unigenes (DEUs) were
      detected in the early, middle and mature growth phases, respectively. Among them,
      many DEUs were implicated in controlling the biosynthesis and composition of
      flavonoids from the budding to full blooming stages during flower development.
      Furthermore, the expression patterns of 12 unigenes involved in flavonoid
      biosynthesis were generally validated by using quantitative real time PCR. These
      findings could shed light on the molecular basis of flavonoid biosynthesis in C.
      morifolium 'Chuju' and provide a genetic resource for breeding varieties with
      improved nutritional quality.

PMID- 30194354
TI  - Cell type-resolved human lung lipidome reveals cellular cooperation in lung
      function.
AB  - Cell type-resolved proteome analyses of the brain, heart and liver have been
      reported, however a similar effort on the lipidome is currently lacking. Here we
      applied liquid chromatography-tandem mass spectrometry to characterize the
      lipidome of major lung cell types isolated from human donors, representing the
      first lipidome map of any organ. We coupled this with cell type-resolved
      proteomics of the same samples (available at Lungmap.net). Complementary
      proteomics analyses substantiated the functional identity of the isolated cells.
      Lipidomics analyses showed significant variations in the lipidome across major
      human lung cell types, with differences most evident at the subclass and intra
      subclass (i.e. total carbon length of the fatty acid chains) level. Further,
      lipidomic signatures revealed an overarching posture of high cellular cooperation
      within the human lung to support critical functions. Our complementary cell type
      resolved lipid and protein datasets serve as a rich resource for analyses of
      human lung function.

PMID- 30194356
TI  - Multiridge Method for Studying Ground-Deformation Sources: Application to
      Volcanic Environments.
AB  - Volcanic phenomena are currently monitored by the detection of physical and
      chemical observations. Generally, the ground deformation field is the most
      relevant shallow expression of the geometric and physical parameters variations
      in the magmatic reservoir. In this study, we propose a novel method for the
      direct estimation of the geometric parameters of sources responsible for volcanic
      ground deformation detected via the DInSAR technique. Starting with the
      biharmonic properties of the deformation field, we define an approach based on
      the Multiridge and ScalFun methods to achieve relevant information about both the
      positions and shapes of active sources, such as the Mogi source. Our methodology
      is definitely different from the methods currently used for modeling ground
      deformation sources, mainly based on forward or inverse techniques. In fact, (i)
      it does not require any assumptions about the source type, and (ii) it is not
      influenced by the distribution of medium elastic parameters or (iii) the presence
      of high-frequency noise in the dataset. For synthetic cases, we accurately
      estimate the depth to the source within a 3% error. Finally, we study the real
      case of the Okmok volcano ground-deformation field and achieve results compatible
      with those in previous works.

PMID- 30194357
TI  - Construction of Self-defensive Antibacterial and Osteogenic AgNPs/Gentamicin
      Coatings with Chitosan as Nanovalves for Controlled release.
AB  - To solve the Ti implants-associated infection and poor osseointegration problems,
      we have constructed the AgNPs/gentamicin (Gen)-loaded silk fibroin (SF) coating
      with acceptable antibacterial and osteogenic aptitude. Nevertheless, due to
      uncontrollably sustained drug release, this bactericidal coating encountered some
      tricky problems, such as local high Ag concentration, short life-span and
      potential cytotoxicity. In this work, a chitosan (CS) barrier layer was
      constructed to prebuilt the SF-based film by two means, dip-coating (DCS) and
      spin-coating (SCS). Intriguingly, the CS barrier layer constructed by spin
      coating highly improved the hydrophilic and protein-absorbed performances. As
      verified in the release profile, both coatings showed a prolonged and pH
      dependent pattern of Ag+ with an accelerated release in acidic condition. Also,
      the multilayer coating with a SCS barrier layer showed an apparent bacteria
      trigged antibacterial and biofilm-inhibited performances, whereas the
      improvements of antibacterial abilities of DCS coating were limited. The
      mechanisms could be explained that the pH decrease induced by the attachment and
      proliferation of bacteria triggered collapse of CS barrier layer, accelerating
      the release of bactericides. Moreover, benefitted from pH-dependent release
      behavior of Ag and bioactive SCS layer, functional coatings highly enhanced the
      initial adhesion, migration and proliferation of preosteoblast MC3T3-E1 cells,
      and subsequently accelerated osteoblast differentiation (alkaline phosphatase
      production). A relevant aspect of this work was to demonstrate the essential
      effect of reasonable construction of self-defensive barrier layer in achieving
      the balance between the high-efficiency bacterial killing and osteogenic
      activity, and highlighted its excellent potential in clinical applications.

PMID- 30194359
TI  - miR-96 influences RARgamma expression.

PMID- 30194358
TI  - Scaling up electrically synchronized spin torque oscillator networks.
AB  - Synchronized nonlinear oscillators networks are at the core of numerous families
      of applications including phased array wave generators and neuromorphic pattern
      matching systems. In these devices, stable synchronization between large numbers
      of nanoscale oscillators is a key issue that remains to be demonstrated. Here, we
      show experimentally that synchronized spin-torque oscillator networks can be
      scaled up. By increasing the number of synchronized oscillators up to eight, we
      obtain that the emitted power and the quality factor increase linearly with the
      number of oscillators. Even more importantly, we demonstrate that the stability
      of synchronization in time exceeds 1.6 milliseconds corresponding to 105 periods
      of oscillation. Our study demonstrates that spin-torque oscillators are suitable
      for applications based on synchronized networks of oscillators.

PMID- 30194361
TI  - CSF1 drives pain in arthritis.

PMID- 30194360
TI  - High HMGB1 levels in sputum are related to pneumococcal bacteraemia but not to
      disease severity in community-acquired pneumonia.
AB  - During bacterial infections, damage-associated molecular patterns (DAMPs) and
      pathogen-associated molecular patterns (PAMPs) activate immune cells. Here, we
      investigated whether plasma and sputum levels of High Mobility Group Box 1
      (HMGB1), a prototypic DAMP, are associated with disease severity and aetiology in
      community-acquired pneumonia (CAP). In addition, in patients with pneumococcal
      CAP, the impact of the level of sputum lytA DNA load, a PAMP, was investigated.
      We studied patients hospitalised for bacterial CAP (n = 111), and samples were
      collected at admission. HMGB1 was determined by enzyme-linked immunosorbent
      assays, and pneumococcal lytA DNA load was determined by quantitative polymerase
      chain reaction. Plasma and sputum HMGB1 levels did not correlate to disease
      severity (pneumonia severity index or presence of sepsis), but high sputum HMGB1
      level was correlated to pneumococcal aetiology (p = 0.002). In pneumococcal
      pneumonia, high sputum lytA DNA load was associated with respiratory failure (low
      PaO2/FiO2 ratio; p = 0.019), and high sputum HMGB1 level was associated with
      bacteraemia (p = 0.006). To conclude, high sputum HMGB1 was not associated with
      severe disease, but with pneumococcal bacteraemia, indicating a potential role
      for HMGB1 in bacterial dissemination. High sputum lytA was associated with severe
      disease.

PMID- 30194362
TI  - Rewiring urea cycle metabolism in cancer to support anabolism.
AB  - Cancer cells reprogramme metabolism to maximize the use of nitrogen and carbon
      for the anabolic synthesis of macromolecules that are required during tumour
      proliferation and growth. To achieve this aim, one strategy is to reduce
      catabolism and nitrogen disposal. The urea cycle (UC) in the liver is the main
      metabolic pathway to convert excess nitrogen into disposable urea. Outside the
      liver, UC enzymes are differentially expressed, enabling the use of nitrogen for
      the synthesis of UC intermediates that are required to accommodate cellular
      needs. Interestingly, the expression of UC enzymes is altered in cancer,
      revealing a revolutionary mechanism to maximize nitrogen incorporation into
      biomass. In this Review, we discuss the metabolic benefits underlying UC
      deregulation in cancer and the relevance of these alterations for cancer
      diagnosis and therapy.

PMID- 30194363
TI  - Prevalence and Possible Factors of Myopia in Norwegian Adolescents.
AB  - East Asia has experienced an excessive increase in myopia in the past decades
      with more than 80% of the younger generation now affected. Environmental and
      genetic factors are both assumed to contribute in the development of refractive
      errors, but the etiology is unknown. The environmental factor argued to be of
      greatest importance in preventing myopia is high levels of daylight exposure. If
      true, myopia prevalence would be higher in adolescents living in high latitude
      countries with fewer daylight hours in the autumn-winter. We examined the
      prevalence of refractive errors in a representative sample of 16-19-year-old
      Norwegian Caucasians (n = 393, 41.2% males) in a representative region of Norway
      (60 degrees  latitude North). At this latitude, autumn-winter is 50 days longer
      than summer. Using gold-standard methods of cycloplegic autorefraction and ocular
      biometry, the overall prevalence of myopia [spherical equivalent refraction (SER)
      <=-0.50 D] was 13%, considerably lower than in East Asians. Hyperopia (SER >= +
      0.50 D), astigmatism (>=1.00 DC) and anisometropia (>=1.00 D) were found in 57%,
      9% and 4%. Norwegian adolescents seem to defy the world-wide trend of increasing
      myopia. This suggests that there is a need to explore why daylight exposure
      during a relatively short summer outweighs that of the longer autumn-winter.

PMID- 30194364
TI  - Ultraviolet exposure has an epigenetic effect on a Batesian mimetic trait in the
      butterfly Papilio polytes.
AB  - Wing polymorphism of butterflies provides a good system in which to study
      adaptation. The Asian Batesian mimic butterfly Papilio polytes has unmelanized,
      putative mimetic red spots on its black hind wings. The size of those red spots
      is non-heritable but it is highly polymorphic, the adaptive significance of which
      is unknown. We hypothesized that under strong ultraviolet (UV) irradiation,
      butterflies develop a wider melanized black area to protect the wings from UV
      damage, and as a result express smaller mimetic red spots. Our field survey on
      Okinawa Island revealed a negative relationship between the sizes of the red spot
      and the black area in the wings. The size varied seasonally and was negatively
      correlated with the intensity of solar UV radiation at the time of capture.
      Laboratory experiments revealed that the size was reduced by strong UV
      irradiation not only of the eggs and larvae, but also of their mothers through a
      putative epigenetic mechanism. The flexible phenotypic expression of the red
      spots in P. polytes suggests a trade-off between protection against UV damage and
      predation avoidance, and provides a new insight into the evolution of Batesian
      mimicry.

PMID- 30194365
TI  - Using high-throughput sequencing to investigate the factors structuring genomic
      variation of a Mediterranean grasshopper of great conservation concern.
AB  - Inferring the demographic history of species is fundamental for understanding
      their responses to past climate/landscape alterations and improving our
      predictions about the future impacts of the different components of ongoing
      global change. Estimating the time-frame at which population fragmentation took
      place is also critical to determine whether such process was shaped by ancient
      events (e.g. past climate/geological changes) or if, conversely, it was driven by
      recent human activities (e.g. habitat loss). We employed genomic data (ddRAD-Seq)
      to determine the factors shaping contemporary patterns of genetic variation in
      the Iberian cross-backed grasshopper Dociostaurus crassiusculus, an endangered
      species with limited dispersal capacity and narrow habitat requirements. Our
      analyses indicate the presence of two ancient lineages and three genetic clusters
      resulted from historical processes of population fragmentation (~18-126 ka) that
      predate the Anthropocene. Landscape genetic analyses indicate that the limits of
      major river basins are the main geographical feature explaining large-scale
      patterns of genomic differentiation, with no apparent effect of human-driven
      habitat fragmentation. Overall, our study highlights the importance of detailed
      phylogeographic, demographic and spatially-explicit landscape analyses to
      identify evolutionary significant units and determine the relative impact of
      historical vs. anthropogenic factors on processes of genetic fragmentation in
      taxa of great conservation concern.

PMID- 30194366
TI  - Elusive mitochondrial connection to inflammation uncovered.

PMID- 30194367
TI  - Protein complexes assemble as they are being made.

PMID- 30194368
TI  - Receptor becomes a ligand to control bone remodelling.

PMID- 30194369
TI  - Antagonistic chemical coupling in self-reconfigurable host-guest protocells.
AB  - Fabrication of compartmentalised chemical systems with nested architectures and
      biomimetic properties has important implications for controlling the positional
      assembly of functional components, spatiotemporal regulation of enzyme cascades
      and modelling of proto-organelle behaviour in synthetic protocells. Here, we
      describe the spontaneous capture of glucose oxidase-containing proteinosomes in
      pH-sensitive fatty acid micelle coacervate droplets as a facile route to multi
      compartmentalised host-guest protocells capable of antagonistic chemical and
      structural coupling. The nested system functions co-operatively at low-substrate
      turnover, while high levels of glucose give rise to pH-induced disassembly of the
      droplets, release of the incarcerated proteinosomes and self-reconfiguration into
      spatially organised enzymatically active vesicle-in-proteinosome protocells. Co
      encapsulation of antagonistic enzymes within the proteinosomes produces a
      sequence of self-induced capture and host-guest reconfiguration. Taken together,
      our results highlight opportunities for the fabrication of self-reconfigurable
      host-guest protocells and provide a step towards the development of protocell
      populations exhibiting both synergistic and antagonistic modes of interaction.

PMID- 30194370
TI  - Fat intake during pregnancy and risk of preeclampsia: a prospective cohort study
      in Denmark.
AB  - BACKGROUND: Previous studies suggest that eicosapentaenoic acid (EPA),
      docosahexaenoic acid (DHA), and alpha-linolenic acid (ALA), may decrease the risk
      of preeclampsia, but many suffer from important methodological limitations.
      METHODS: We prospectively examined the association between fat intake during
      pregnancy and preeclampsia and among 65,220 singleton pregnancies in the Danish
      National Birth Cohort (1996-2002). Women were asked to report their diet around
      gestation week 20 with a food frequency questionnaire. Preeclampsia diagnosis was
      obtained via linkage with the Danish National Patient Registry. We estimated
      relative risks (RR) and 95% confidence intervals (95% CI) of preeclampsia and
      severe preeclampsia according to fat intake using logistic regression models with
      generalized estimating equations to account for repeated pregnancies per woman
      while adjusting for potential confounders. RESULTS: We documented 1302 cases of
      preeclampsia, including 301 cases of severe preeclampsia. Intake of long-chain
      omega-3 fatty acids was associated to preeclampsia. Women in the top quintile of
      DHA intake had a lower risk of preeclampsia (RR 0.67 (0.51-0.89)) and severe
      preeclampsia (RR 0.46 (0.25-0.83)) than women in the bottom quintile. Women who
      met daily recommended intake of EPA+DHA according to the Dietary Guidelines for
      Americans (>=250 mg/day), had a lower risk of severe preeclampsia (RR 0.77 (0.60
      0.99)), but not of preeclampsia (RR 0.93 (0.82-1.05)). Conversely, ALA intake was
      associated with higher risk of severe preeclampsia (RR 1.71 (1.07-2.75)).
      CONCLUSIONS: Higher intake of DHA is inversely related to preeclampsia and severe
      preeclampsia, whereas ALA increases the risk of severe preeclampsia among Danish
      women.

PMID- 30194372
TI  - Long-term outcome after grafting with small intestinal submucosa and collagen
      fleece in patients with Peyronie's disease: a matched pair analysis.
AB  - Advanced Peyronie's disease (PD) with severe penile curvature requires grafting
      following plaque incision or partial plaque excision. So far, the ideal graft
      material has not been identified although various grafts have been studied. In
      this first matched pair analysis we compared the outcome after grafting with
      small intestinal submucosa (SIS) and self-adhesive collagen fleece (CF). We
      retrospectively identified 43 patients after SIS grafting with complete follow-up
      data sets to be eligible for the present study. A total of 43 patients after CF
      grafting were matched case by case to the SIS group using the degree of
      preoperative penile curvature as the primary matching factor. Postoperative
      outcome was compared with the focus on penile straightening, penile length,
      potency, relapse rates and long-term complications. Median degree of curvature
      was 80 degrees  in each group. Mean follow-up periods were 31 months after SIS
      and 39 months after CF grafting. The CF grafting procedure was significantly
      faster than SIS grafting (80 vs. 104 min, p < 0.001). No major short-term
      complications were observed. Both techniques gained good long-term penile
      straightening rates. Relapse of penile curvature was observed after SIS grafting
      only. Postoperative penile shortening occurred more often after SIS grafting (28%
      vs. 5%, p = 0.007). With a mean preoperative IIEF-5 score of 16, the SIS cohort
      significantly differed from the CF cohort with a mean IIEF-5 score of 19 (p =
      0.016). The median IIEF-5 score improvement was higher after SIS grafting (+4.5
      vs. +1, p = 0.002). Diminished penile sensation was the main long-term side
      effect with low rates after both procedures (9% and 7% in the SIS and CF group
      respectively, p = 0.100). In this first matched pair analysis both techniques
      showed promising long-term results. CF seems to have advantages regarding
      duration of surgery and preserving penile length. More comparative studies with
      larger collectives are desirable.

PMID- 30194373
TI  - Penile duplex: clinical indications and application.

PMID- 30194371
TI  - Sub-2 A Ewald curvature corrected structure of an AAV2 capsid variant.
AB  - Single-particle cryogenic electron microscopy (cryo-EM) provides a powerful
      methodology for structural biologists, but the resolutions typically attained
      with experimentally determined structures have lagged behind microscope
      capabilities. Here, we exploit several technical advances to improve resolution,
      including per-particle contrast transfer function (CTF) refinement and correction
      for Ewald sphere curvature. The latter is demonstrated with several experimental
      samples and should become more standard as resolutions increase or at lower
      microscope accelerating voltages. The combined application of the described
      methods to micrographs recorded on a Titan Krios enables structure determination
      at ~1.86-A resolution of an adeno-associated virus serotype 2 variant (AAV2), an
      important gene-delivery vehicle. The resulting structural details provide an
      improved model for understanding the biology of AAV that will guide future vector
      development for gene therapy.

PMID- 30194374
TI  - Compartmentalised RNA catalysis in membrane-free coacervate protocells.
AB  - Phase separation of mixtures of oppositely charged polymers provides a simple and
      direct route to compartmentalisation via complex coacervation, which may have
      been important for driving primitive reactions as part of the RNA world
      hypothesis. However, to date, RNA catalysis has not been reconciled with
      coacervation. Here we demonstrate that RNA catalysis is viable within coacervate
      microdroplets and further show that these membrane-free droplets can selectively
      retain longer length RNAs while permitting transfer of lower molecular weight
      oligonucleotides.

PMID- 30194375
TI  - Parameter-Free Multiscale Simulation Realising Quantitative Prediction of Hole
      and Electron Mobilities in Organic Amorphous System with Multiple Frontier
      Orbitals.
AB  - In amorphous organic semiconducting systems, hole and electron transfer has been
      considered to occur based on the overlap of highest occupied molecular orbitals
      (HOMOs) and that of lowest unoccupied molecular orbitals (LUMOs) between two
      adjacent molecules, respectively. Other molecular orbitals (MOs), HOMO-1, HOMO-2,
      ... and LUMO+1, LUMO+2, ..., have been neglected in charge transport
      calculations. However, these MOs could potentially contribute to charge
      transport. In this study, our multiscale simulations show that carriers are
      effectively transported not only via HOMOs or LUMOs but also via other MOs when
      the MOs are close in energy. Because these multiple MOs are active in charge
      transports, here we call them multiple frontier orbitals. Molecules with multiple
      frontier orbitals are found to possess high carrier mobility. The findings in
      this study provide guidelines to aid design of materials with excellent charge
      transport properties.

PMID- 30194376
TI  - Organizational principles of multidimensional predictions in human auditory
      attention.
AB  - Anticipating the future rests upon our ability to exploit contextual cues and to
      formulate valid internal models or predictions. It is currently unknown how
      multiple predictions combine to bias perceptual information processing, and in
      particular whether this is determined by physiological constraints, behavioral
      relevance (task demands), or past knowledge (perceptual expertise). In a series
      of behavioral auditory experiments involving musical experts and non-musicians,
      we investigated the respective and combined contribution of temporal and spectral
      predictions in multiple detection tasks. We show that temporal and spectral
      predictions alone systematically increase perceptual sensitivity, independently
      of task demands or expertise. When combined, however, spectral predictions
      benefit more to non-musicians and dominate over temporal ones, and the extent of
      the spectrotemporal synergistic interaction depends on task demands. This
      suggests that the hierarchy of dominance primarily reflects the tonotopic
      organization of the auditory system and that expertise or attention only have a
      secondary modulatory influence.

PMID- 30194377
TI  - Comparison among different diagnostic criteria for chronic ocular graft-versus
      host disease applied with and without pre-transplant ophthalmological
      examination.
AB  - PURPOSE: To compare the proportion and the agreement rate in the diagnosis of
      chronic ocular graft-versus-host disease (GVHD) among three criteria applied with
      and without ophthalmological examination before hematopoietic stem cell
      transplantation (HSCT). METHODS: National Institutes of Health (NIH),
      International Consensus Criteria on ocular GVHD (ICCGVHD) and TFOS Dry Eye
      Workshop (DEWS) II criteria were used for the diagnosis of ocular GVHD according
      to two protocols: ophthalmological examination after HSCT (Protocol A), or before
      and after HSCT (Protocol B). Proportion of GVHD diagnosis and inter-rate
      agreement coefficient Kappa (K) among the criteria were calculated. RESULTS: One
      hundred nine patients undergone HSCT were included. NIH, ICCGVHD and DEWS II
      criteria diagnosed ocular GVHD in 14.7%, 17.4% and 59.6% of the patients
      (Protocol A), whereas in 11.9%, 15.6% and 33.0% of the HSCT patients (Protocol
      B). The coefficient K for the proportion of patients diagnosed with ocular GVHD
      by NIH and ICCGVHD criteria was K = 0.626 (Protocol A) and K = 0.615 (Protocol
      B). The K coefficient by NIH and DEWS II criteria was K = 0.144 (Protocol A), and
      K = 0.233 (Protocol B). The K coefficient by ICCGVHD and DEWS II criteria was K =
      0.250 (Protocol A) and K = 0.499 (Protocol B). The K coefficient for ocular GVHD
      diagnosis applying Protocol A and B was K = 0.881 if NIH criteria were used, K =
      0.933 if ICCGVHD criteria were used and K = 0.501 if DEWS II criteria were used.
      CONCLUSIONS: The diagnosis of ocular GVHD varied significantly in our cohort of
      hematological patients according to both the diagnostic criteria used and the
      visit protocols applied.

PMID- 30194378
TI  - Van gogh and the obsession of yellow: style or side effect.

PMID- 30194379
TI  - A novel and effective ophthalmology morbidity and mortality meeting.

PMID- 30194380
TI  - Clinical efficacy of eplerenone versus placebo for central serous
      chorioretinopathy: study protocol for the VICI randomised controlled trial.
AB  - AIMS: Chronic central serous chorioretinopathy (CSCR) is poorly understood. Fluid
      accumulates in the subretinal space and retinal pigment epitheliopathy and
      neurosensory atrophy may develop. Permanent vision loss occurs in approximately
      one third of cases. There are no effective treatments for CSCR. Recent studies
      have shown the mineralocorticoid receptor antagonist, eplerenone, to be effective
      in resolving subretinal fluid and improving visual acuity. This trial aims to
      compare the safety and efficacy of eplerenone in patients with CSCR in a double
      masked randomised placebo-controlled trial. METHODS: Patients are randomised 1:1
      to receive eplerenone with usual care or placebo with usual care for 12 months;
      25 mg per day for 1 week, then 50 mg per day up to 12 months (unless discontinued
      for safety or resolution of CSCR). Key eligibility criteria are: age 18-60 years,
      one eye with CSCR for >=4 months duration, best-corrected visual acuity (BCVA)
      >53 and <86 letters and no previous treatment. The primary outcome is BCVA at 12
      months. Secondary outcomes include resolution of subretinal fluid, development of
      macular atrophy, subfoveal choroidal thickness, changes in low luminance visual
      acuity, health-related quality of life and safety. CONCLUSIONS: Recruitment is
      complete but was slower than expected. We maintained the eligibility criteria to
      ensure participants had 'true' CSCR and recruited additional centres. Effective
      distribution of the investigational medicinal product (IMP) was achieved by
      implementing a database to manage ordering and accountability of IMP packs. The
      results will provide adequately powered evidence to inform clinical decisions
      about using eplerenone to treat patients with CSCR.

PMID- 30194381
TI  - A new sauropodiform dinosaur with a 'sauropodan' skull from the Lower Jurassic
      Lufeng Formation of Yunnan Province, China.
AB  - The Early Jurassic Lufeng Formation of Yunnan Province in southwestern China is
      one of the best fossil localities in the world for understanding the early
      radiation of sauropodomorph dinosaurs. It has yielded a rich assemblage of
      complete and three-dimensionally preserved skeletons of herbivorous dinosaurs
      that provide crucial morphological information for systematic and evolutionary
      studies. Here we describe a new taxon, Yizhousaurus sunae gen. et sp. nov.,
      represented by a nearly complete skeleton with an exquisitely preserved skull and
      mandible. Yizhousaurus is distinguished from other non-sauropodan sauropodomorphs
      by a unique combination of plesiomorphic and apomorphic features, which increases
      our understanding of the anatomical variation on the relatively conservative
      'prosauropod' cranial plan. Phylogenetic analysis resolves Yizhousaurus as a
      sauropodiform, showcasing a mosaic character suite combining plesiomorphic states
      in the postcranial skeleton with some more 'sauropodan'-like features in the
      skull. Furthermore, Yizhousaurus is placed closer to the base of Sauropoda than
      other non-sauropodan sauropodomorphs currently known from the Lufeng Formation,
      adding another taxon to enrich the Lower Jurassic Lufeng dinosaur fauna.

PMID- 30194382
TI  - Deep soils modify environmental consequences of increased nitrogen fertilizer use
      in intensifying Amazon agriculture.
AB  - Agricultural intensification offers potential to grow more food while reducing
      the conversion of native ecosystems to croplands. However, intensification also
      risks environmental degradation through emissions of the greenhouse gas nitrous
      oxide (N2O) and nitrate leaching to ground and surface waters. Intensively
      managed croplands and nitrogen (N) fertilizer use are expanding rapidly in
      tropical regions. We quantified fertilizer responses of maize yield, N2O
      emissions, and N leaching in an Amazon soybean-maize double-cropping system on
      deep, highly-weathered soils in Mato Grosso, Brazil. Application of N fertilizer
      above 80 kg N ha-1 yr-1 increased maize yield and N2O emissions only slightly.
      Unlike experiences in temperate regions, leached nitrate accumulated in deep
      soils with increased fertilizer and conversion to cropping at N fertilization
      rates >80 kg N ha-1, which exceeded maize demand. This raises new questions about
      the capacity of tropical agricultural soils to store nitrogen, which may
      determine when and how much nitrogen impacts surface waters.

PMID- 30194383
TI  - Mapping molecular landmarks of human skeletal ontogeny and pluripotent stem cell
      derived articular chondrocytes.
AB  - Tissue-specific gene expression defines cellular identity and function, but
      knowledge of early human development is limited, hampering application of cell
      based therapies. Here we profiled 5 distinct cell types at a single fetal stage,
      as well as chondrocytes at 4 stages in vivo and 2 stages during in vitro
      differentiation. Network analysis delineated five tissue-specific gene modules;
      these modules and chromatin state analysis defined broad similarities in gene
      expression during cartilage specification and maturation in vitro and in vivo,
      including early expression and progressive silencing of muscle- and bone-specific
      genes. Finally, ontogenetic analysis of freshly isolated and pluripotent stem
      cell-derived articular chondrocytes identified that integrin alpha 4 defines 2
      subsets of functionally and molecularly distinct chondrocytes characterized by
      their gene expression, osteochondral potential in vitro and proliferative
      signature in vivo. These analyses provide new insight into human musculoskeletal
      development and provide an essential comparative resource for disease modeling
      and regenerative medicine.

PMID- 30194384
TI  - MMP8 and MMP9 gene polymorphisms were associated with breast cancer risk in a
      Chinese Han population.
AB  - Matrix metalloproteinases (MMPs) are a group of zinc-dependent endopeptidases
      that can breakdown almost all extracellular matrix components. MMP8 and MMP9 have
      been shown to be associated with breast cancer (BC) risk in European and American
      populations. However, few studies have focused on the polymorphisms of MMP8 and
      MMP9 in Chinese Han BC patients. We investigated nine single nucleotide
      polymorphisms (SNPs) in 571 BC cases and 578 controls to evaluating their
      association with risk of BC. The frequency of the "A" allele of rs3787268 was
      significantly lower in BC cases than in controls (P = 0.025). In the genetic
      model analysis, the minor allele "T" of rs11225394 in MMP8 was associated with
      increased risk of BC under the recessive model (P = 0.019), and the minor allele
      "A" of rs3787268 was associated with decreased risk of BC under the dominant
      model (P = 0.014). Additionally, the haplotype "AGTCA" constructed by rs3740938,
      rs2012390, rs1940475, rs11225394, and rs11225395 and the haplotype "CCG"
      constructed by rs3918249, rs3918254 and rs3787268 were associated with increased
      risk of BC (P < 0.05). Our data showed that polymorphisms of MMP8 and MMP9 may be
      associated with BC risk in the Chinese Han population.

PMID- 30194385
TI  - Novel insight into the reaction of nitro, nitroso and hydroxylamino
      benzothiazinones and of benzoxacinones with Mycobacterium tuberculosis DprE1.
AB  - Nitro-substituted 1,3-benzothiazinones (nitro-BTZs) are mechanism-based covalent
      inhibitors of Mycobacterium tuberculosis decaprenylphosphoryl-beta-D-ribose-2'
      oxidase (DprE1) with strong antimycobacterial properties. We prepared a number of
      oxidized and reduced forms of nitro-BTZs to probe the mechanism of inactivation
      of the enzyme and to identify opportunities for further chemistry. The kinetics
      of inactivation of DprE1 was examined using an enzymatic assay that monitored
      reaction progress up to 100 min, permitting compound ranking according to
      kinact/Ki values. The side-chain at the 2-position and heteroatom identity at the
      1-position of the BTZs were found to be important for inhibitory activity. We
      obtained crystal structures with several compounds covalently bound. The data
      suggest that steps upstream from the covalent end-points are likely the key
      determinants of potency and reactivity. The results of protein mass spectrometry
      using a 7-chloro-nitro-BTZ suggest that nucleophilic reactions at the 7-position
      do not operate and support a previously proposed mechanism in which BTZ
      activation by a reduced flavin intermediate is required. Unexpectedly, a
      hydroxylamino-BTZ showed time-dependent inhibition and mass spectrometry
      corroborated that this hydroxylamino-BTZ is a mechanism-based suicide inhibitor
      of DprE1. With this BTZ derivative, we propose a new covalent mechanism of
      inhibition of DprE1 that takes advantage of the oxidation cycle of the enzyme.

PMID- 30194387
TI  - Mechanism(s) of action of heavy metals to investigate the regulation of plastidic
      glucose-6-phosphate dehydrogenase.
AB  - The regulation of recombinant plastidic glucose-6P dehydrogenase from Populus
      trichocarpa (PtP2-G6PDH - EC 1.1.1.49) was investigated by exposing wild type and
      mutagenized isoforms to heavy metals. Nickel and Cadmium caused a marked decrease
      in PtP2-G6PDH WT activity, suggesting their poisoning effect on plant enzymes;
      Lead (Pb++) was substantially ineffective. Copper (Cu++) and Zinc (Zn++)
      exposition resulted in strongest decrease in enzyme activity, thus suggesting a
      physiological competition with Magnesium, a well-known activator of G6PDH
      activity. Kinetic analyses confirmed a competitive inhibition by Copper, and a
      mixed inhibition by (Cd++). Mutagenized enzymes were differently affected by HMs:
      the reduction of disulfide (C175-C183) exposed the NADP+ binding sites to metals;
      C145 participates to NADP+ cofactor binding; C194 and C242 are proposed to play a
      role in the regulation of NADP+/NADPH binding. Copper (and possibly Zinc) is able
      to occupy competitively Magnesium (Mg++) sites and/or bind to NADP+, resulting in
      a reduced access of NADP+ sites on the enzyme. Hence, heavy metals could be used
      to describe specific roles of cysteine residues present in the primary protein
      sequence; these results are discussed to define the biochemical mechanism(s) of
      inhibition of plant plastidic G6PDH.

PMID- 30194386
TI  - Ventral hippocampal OLM cells control type 2 theta oscillations and response to
      predator odor.
AB  - Dorsal and ventral hippocampus regions exert cognition and emotion-related
      functions, respectively. Since both regions display rhythmic activity, specific
      neural oscillatory pacemakers may underlie their functional dichotomy. Type 1
      theta oscillations are independent of cholinergic transmission and are observed
      in the dorsal hippocampus during movement and exploration. In contrast, type 2
      theta depends on acetylcholine and appears when animals are exposed to
      emotionally laden contexts such as a predator presence. Despite its involvement
      in emotions, type 2 theta has not been associated with the ventral hippocampus.
      Here, we show that optogenetic activation of oriens-lacunosum moleculare (OLM)
      interneurons in the ventral hippocampus drives type 2 theta. Moreover, we found
      that type 2 theta generation is associated with increased risk-taking behavior in
      response to predator odor. These results demonstrate that two theta oscillations
      subtypes originate in the two hippocampal regions that predominantly underlie
      either cognitive or emotion-related functions.

PMID- 30194388
TI  - Selective sorting of polymers with different terminal groups using metal-organic
      frameworks.
AB  - Separation of high-molecular-weight polymers differing just by one monomeric unit
      remains a challenging task. Here, we describe a protocol using metal-organic
      frameworks (MOFs) for the efficient separation and purification of mixtures of
      polymers that differ only by their terminal groups. In this process, polymer
      chains are inserted by threading one of their extremities through a series of MOF
      nanowindows. Selected termini can be adjusted by tuning the MOF structure, and
      the insertion methodology. Accordingly, MOFs with permanently opened pores allow
      for the complete separation of poly(ethylene glycol) (PEG) based on steric
      hindrance of the terminal groups. Excellent separation is achieved, even for high
      molecular weights (20 kDa). Furthermore, the dynamic character of a flexible MOF
      is used to separate PEG mixtures with very similar terminal moieties, such as OH,
      OMe, and OEt, as the slight difference of polarity in these groups significantly
      changes the pore opening kinetics.

PMID- 30194389
TI  - Potent PDZ-Domain PICK1 Inhibitors that Modulate Amyloid Beta-Mediated Synaptic
      Dysfunction.
AB  - Protein interacting with C kinase (PICK1) is a scaffolding protein that is
      present in dendritic spines and interacts with a wide array of proteins through
      its PDZ domain. The best understood function of PICK1 is regulation of
      trafficking of AMPA receptors at neuronal synapses via its specific interaction
      with the AMPA GluA2 subunit. Disrupting the PICK1-GluA2 interaction has been
      shown to alter synaptic plasticity, a molecular mechanism of learning and memory.
      Lack of potent, selective inhibitors of the PICK1 PDZ domain has hindered efforts
      at exploring the PICK1-GluA2 interaction as a therapeutic target for neurological
      diseases. Here, we report the discovery of PICK1 small molecule inhibitors using
      a structure-based drug design strategy. The inhibitors stabilized surface GluA2,
      reduced Abeta-induced rise in intracellular calcium concentrations in cultured
      neurons, and blocked long term depression in brain slices. These findings
      demonstrate that it is possible to identify potent, selective PICK1-GluA2
      inhibitors which may prove useful for treatment of neurodegenerative disorders.

PMID- 30194390
TI  - Theoretical investigation of heterogeneous wettability in porous media using NMR.
AB  - It is highly important to understand the heterogeneous wettability properties of
      porous media for enhanced oil recovery (EOR). However, wettability measurements
      are still challenging in directly investigating the wettability of porous media.
      In this paper, we propose a multidimensional nuclear magnetic resonance (NMR)
      method and the concept of apparent contact angles to characterize the
      heterogeneous wettability of porous media. The apparent contact angle, which is
      determined by both the wetting surface coverage and the local wettability
      (wetting contact angles of each homogeneous wetting regions or wetting patches),
      is first introduced as an indicator of the heterogeneous wettability of porous
      media using the NMR method. For homogeneously wetting patches, the relaxation
      time ratio T1/T2 is employed to probe the local wettabiity of wetting patches.
      The T2 - D is introduced to obtain the wetting surface coverage using the
      effective relaxivity. Numerical simulations are conducted to validate this
      method.

PMID- 30194391
TI  - Investigation of the hydrophobic and acoustic properties of bio windmill palm
      materials.
AB  - Windmill palm fibers are an abundant lignin-cellulose fiber resource. Single palm
      fibers can be prepared using an alkali treatment method. However, these fibers
      have hydrophilic surfaces, and following drying the fibers exhibit serious
      aggregation. This limits their application as acoustic materials. In this work,
      both alkali and acetylation treatments were used to modify the characteristics of
      windmill palm fibers. These treatments caused the surface of the fibers to become
      hydrophobic and increased the specific area and free vacuum space of the fibers,
      thus lowering energy loss. Scanning electron microscope observations combined
      with Fourier-transform infrared spectroscopy showed that the acetylation
      treatment resulted in the substitution of hydroxyl groups with acetyl groups, and
      the formation of nanoscale pores (10~50 nm). The results of the moisture
      absorption and contact-angle tests showed that the moisture regain value
      decreased to 3.86%, and the contact angle increased to above 140 degrees  after
      acetylation treatment. The average sound absorption coefficients of the alkalized
      and acetylated nonwoven fabrics were 0.31 and 0.36, respectively. The masses of
      the acetylated samples were 50% those of the windmill palm sheath samples.

PMID- 30194393
TI  - Facile and scalable production of heterostructured ZnS-ZnO/Graphene nano
      photocatalysts for environmental remediation.
AB  - A facile and eco-friendly strategy is described for the synthesis of ZnS
      ZnO/graphene heterostructured nano-photocatalysts for the first time. This
      solvent-free and technologically scalable method involves solid-state mixing of
      graphite oxide (GO), Zn salt and surfeit yet non-toxic elemental sulfur using
      ball-milling followed by thermal annealing. The as-formed hybrids are composed of
      uniformly distributed in-situ formed ZnS-ZnO nanoparticles simultaneously within
      the thermally reduced GO (graphene) matrix. A series of hybrid compositions with
      varying content of ZnS/ZnO and graphene were prepared and thoroughly
      characterized. Further, the effect of heterostructure composition on the
      photocatalytic properties was investigated under visible-light illumination. The
      synergistic ZnS-ZnO/graphene hybridization promoted the band-gap narrowing
      compared to the pristine ZnS nanoparticles. The ZnS:ZnO composition was
      controlled by graphite oxide under thermal treatment and observed to be a crucial
      factor in enhancement of photocatalytic activity. As a proof of concept, the
      phase optimized and surface enhanced ZnS-ZnO/graphene nano-photocatalysts was
      tested towards visible light driven photocatalytic degradation of environmentally
      harmful organic dyes and toxic phenol molecules from aqueous media. The presented
      cost-effective strategy provides high potential in large-scale production of
      heterostructured nano-photocatalysts for environmental remediation and
      photocatalytic greener production of hydrogen.

PMID- 30194394
TI  - Projected amplification of food web bioaccumulation of MeHg and PCBs under
      climate change in the Northeastern Pacific.
AB  - Climate change increases exposure and bioaccumulation of pollutants in marine
      organisms, posing substantial ecophysiological and ecotoxicological risks. Here,
      we applied a trophodynamic ecosystem model to examine the bioaccumulation of
      organic mercury (MeHg) and polychlorinated biphenyls (PCBs) in a Northeastern
      Pacific marine food web under climate change. We found largely heterogeneous
      sensitivity in climate-pollution impacts between chemicals and trophic groups.
      Concentration of MeHg and PCBs in top predators, including resident killer
      whales, is projected to be amplified by 8 and 3%, respectively, by 2100 under a
      high carbon emission scenario (Representative Concentration Pathway 8.5) relative
      to a no-climate change control scenario. However, the level of amplification
      increases with higher carbon emission scenario for MeHg, but decreases for PCBs.
      Such idiosyncratic responses are shaped by the differences in bioaccumulation
      pathways between MeHg and PCBs, and the modifications of food web dynamics
      between different levels of climate change. Climate-induced pollutant
      amplification in mid-trophic level predators (Chinook salmon) are projected to be
      higher (~10%) than killer whales. Overall, the predicted trophic magnification
      factor is ten-fold higher in MeHg than in PCBs under high CO2 emissions. This
      contribution highlights the importance of understanding the interactions with
      anthropogenic organic pollutants in assessing climate risks on marine ecosystems.

PMID- 30194392
TI  - Neuronal microRNA regulation in Experimental Autoimmune Encephalomyelitis.
AB  - Multiple sclerosis (MS) is an autoimmune, neurodegenerative disease but the
      molecular mechanisms underlying neurodegenerative aspects of the disease are
      poorly understood. microRNAs (miRNAs) are powerful regulators of gene expression
      that regulate numerous mRNAs simultaneously and can thus regulate programs of
      gene expression. Here, we describe miRNA expression in neurons captured from mice
      subjected to experimental autoimmune encephalomyelitis (EAE), a model of central
      nervous system (CNS) inflammation. Lumbar motor neurons and retinal neurons were
      laser captured from EAE mice and miRNA expression was assessed by next-generation
      sequencing and validated by qPCR. We describe 14 miRNAs that are differentially
      regulated in both neuronal subtypes and determine putative mRNA targets though in
      silico analysis. Several upregulated neuronal miRNAs are predicted to target
      pathways that could mediate repair and regeneration during EAE. This work
      identifies miRNAs that are affected by inflammation and suggests novel candidates
      that may be targeted to improve neuroprotection in the context of pathological
      inflammation.

PMID- 30194395
TI  - Planar coil-based contact-mode magnetic stimulation: synaptic responses in
      hippocampal slices and thermal considerations.
AB  - Implantable magnetic stimulation is an emerging type of neuromodulation using
      coils that are small enough to be implanted in the brain. A major advantage of
      this method is that stimulation performance could be sustained even though the
      coil is encapsulated by gliosis due to foreign body reactions. Magnetic fields
      can induce indirect electric fields and currents in neurons. Compared to
      transcranial magnetic stimulation, the coil size used in implantable magnetic
      stimulation can be greatly reduced. However, the size reduction is accompanied by
      an increase in coil resistance. Hence, the coil could potentially damage neurons
      from the excess heat generated. Therefore, it is necessary to study the
      stimulation performance and possible thermal damage by implantable magnetic
      stimulation. Here, we devised contact-mode magnetic stimulation (CMS), wherein
      magnetic stimulation was applied to hippocampal slices through a customized
      planar-type coil underneath the slice in the contact mode. With acute hippocampal
      slices, we investigated the synaptic responses to examine the field excitatory
      postsynaptic responses of CMS and the temperature rise during CMS. A long-lasting
      synaptic depression was exhibited in the CA1 stratum radiatum after CMS, while
      the temperature remained in a safe range so as not to seriously affect the neural
      responses.

PMID- 30194398
TI  - Rivaroxaban for prevention of VTE.

PMID- 30194397
TI  - Unilateral Exoskeleton Imposes Significantly Different Hemispherical Effect in
      Parietooccipital Region, but Not in Other Regions.
AB  - In modern society, increasing people suffering from locomotor disabilities need
      an assistive exoskeleton to help them improve or restore ambulation. When walking
      is assisted by an exoskeleton, brain activities are altered as the closed-loop
      between brain and lower limbs is affected by the exoskeleton. Intuitively, a
      unilateral exoskeleton imposes differential effect on brain hemispheres (i.e.,
      hemispherical effect) according to contralateral control mechanism. However, it
      is unclear whether hemispherical effect appears in whole hemisphere or particular
      region. To this end, we explored hemispherical effect on different brain regions
      using EEG data collected from 30 healthy participants during overground walking.
      The results showed that hemispherical effect was significantly different between
      regions when a unilateral exoskeleton was employed for walking assistance and no
      significance was observed for walking without the exoskeleton. Post-hoc t-test
      analysis revealed that hemispherical effect in the parietooccipital region
      significantly differed from other regions. In the parietooccipital region, a
      greater hemispherical effect was observed in beta band for exoskeleton-assisted
      walking compared to walking without exoskeleton, which was also found in the
      source analysis. These findings deepen the understanding of hemispherical effect
      of unilateral exoskeleton on brain and could aid the development of more
      efficient and suitable exoskeleton for walking assistance.

PMID- 30194396
TI  - Variants associating with uterine leiomyoma highlight genetic background shared
      by various cancers and hormone-related traits.
AB  - Uterine leiomyomas are common benign tumors of the myometrium. We performed a
      meta-analysis of two genome-wide association studies of leiomyoma in European
      women (16,595 cases and 523,330 controls), uncovering 21 variants at 16 loci that
      associate with the disease. Five variants were previously reported to confer risk
      of various malignant or benign tumors (rs78378222 in TP53, rs10069690 in TERT,
      rs1800057 and rs1801516 in ATM, and rs7907606 at OBFC1) and four signals are
      located at established risk loci for hormone-related traits (endometriosis and
      breast cancer) at 1q36.12 (CDC42/WNT4), 2p25.1 (GREB1), 20p12.3 (MCM8), and
      6q26.2 (SYNE1/ESR1). Polygenic score for leiomyoma, computed using UKB data, is
      significantly correlated with risk of cancer in the Icelandic population.
      Functional annotation suggests that the non-coding risk variants affect multiple
      genes, including ESR1. Our results provide insights into the genetic background
      of leiomyoma that are shared by other benign and malignant tumors and highlight
      the role of hormones in leiomyoma growth.

PMID- 30194399
TI  - No benefit of rivaroxaban in HF with sinus rhythm.

PMID- 30194400
TI  - Early invasive assessment of NSTE-ACS.

PMID- 30194403
TI  - The birth, evolution and death of metabolic gene clusters in fungi.
AB  - Fungi contain a remarkable diversity of both primary and secondary metabolic
      pathways involved in ecologically specialized or accessory functions. Genes in
      these pathways are frequently physically linked on fungal chromosomes, forming
      metabolic gene clusters (MGCs). In this Review, we describe the diversity in the
      structure and content of fungal MGCs, their population-level and species-level
      variation, the evolutionary mechanisms that underlie their formation, maintenance
      and decay, and their ecological and evolutionary impact on fungal populations. We
      also discuss MGCs from other eukaryotes and the reasons for their preponderance
      in fungi. Improved knowledge of the evolutionary life cycle of MGCs will advance
      our understanding of the ecology of specialized metabolism and of the interplay
      between the lifestyle of an organism and genome architecture.

PMID- 30194402
TI  - Sleep staging using nocturnal sound analysis.
AB  - Sleep staging is essential for evaluating sleep and its disorders. Most sleep
      studies today incorporate contact sensors that may interfere with natural sleep
      and may bias results. Moreover, the availability of sleep studies is limited, and
      many people with sleep disorders remain undiagnosed. Here, we present a
      pioneering approach for rapid eye movement (REM), non-REM, and wake staging
      (macro-sleep stages, MSS) estimation based on sleep sounds analysis. Our working
      hypothesis is that the properties of sleep sounds, such as breathing and
      movement, within each MSS are different. We recorded audio signals, using non
      contact microphones, of 250 patients referred to a polysomnography (PSG) study in
      a sleep laboratory. We trained an ensemble of one-layer, feedforward neural
      network classifiers fed by time-series of sleep sounds to produce real-time and
      offline analyses. The audio-based system was validated and produced an epoch-by
      epoch (standard 30-sec segments) agreement with PSG of 87% with Cohen's kappa of
      0.7. This study shows the potential of audio signal analysis as a simple,
      convenient, and reliable MSS estimation without contact sensors.

PMID- 30194401
TI  - Implications for the impairment of the rapid channel closing of Proteomonas
      sulcata anion channelrhodopsin 1 at high Cl- concentrations.
AB  - Natural anion channelrhodopsins (ACRs) have recently received increased attention
      because of their effectiveness in optogenetic manipulation for neuronal
      silencing. In this study, we focused on Proteomonas sulcata ACR1 (PsuACR1), which
      has rapid channel closing kinetics and a rapid recovery to the initial state of
      its anion channel function that is useful for rapid optogenetic control. To
      reveal the anion concentration dependency of the channel function, we
      investigated the photochemical properties of PsuACR1 using spectroscopic
      techniques. Recombinant PsuACR1 exhibited a Cl- dependent spectral red-shift from
      531 nm at 0.1 mM to 535 nm at 1000 mM, suggesting that it binds Cl- in the
      initial state with a Kd of 5.5 mM. Flash-photolysis experiments revealed that the
      photocycle was significantly changed at high Cl- concentrations, which led not
      only to suppression of the accumulation of the M-intermediate involved in the Cl-
      non-conducting state but also to a drastic change in the equilibrium state of the
      other photo-intermediates. Because of this, the Cl- conducting state is
      protracted by one order of magnitude, which implies an impairment of the rapid
      channel closing of PsuACR1 in the presence of high concentrations of Cl-.

PMID- 30194404
TI  - Clarifying access to data.

PMID- 30194405
TI  - Bringing polygenic risk scores to the clinic.

PMID- 30194406
TI  - Revising salt consumption.

PMID- 30194407
TI  - An option for treatment of multidrug-resistant HIV.

PMID- 30194409
TI  - Restoring sight with native cell reprogramming.

PMID- 30194408
TI  - Modeling tumors and their T cell killers.

PMID- 30194410
TI  - Wound, heal thyself.

PMID- 30194411
TI  - Preconception cold-induced epigenetic inheritance.

PMID- 30194412
TI  - Right data for right patient-a precisionFDA NCI-CPTAC Multi-omics Mislabeling
      Challenge.

PMID- 30194414
TI  - To degrade or not to degrade: mechanisms and significance of endocytic recycling.
AB  - Newly endocytosed integral cell surface proteins are typically either directed
      for degradation or subjected to recycling back to the plasma membrane. The
      sorting of integral cell surface proteins, including signalling receptors,
      nutrient transporters, ion channels, adhesion molecules and polarity markers,
      within the endolysosomal network for recycling is increasingly recognized as an
      essential feature in regulating the complexities of physiology at the cell,
      tissue and organism levels. Historically, endocytic recycling has been regarded
      as a relatively passive process, where the majority of internalized integral
      proteins are recycled via a nonspecific sequence-independent 'bulk membrane flow'
      pathway. Recent work has increasingly challenged this view. The discovery of
      sequence-specific sorting motifs and the identification of cargo adaptors and
      associated coat complexes have begun to uncover the highly orchestrated nature of
      endosomal cargo recycling, thereby providing new insight into the function and
      (patho)physiology of this process.

PMID- 30194413
TI  - Trojan Horse nanotheranostics with dual transformability and multifunctionality
      for highly effective cancer treatment.
AB  - Nanotheranostics with integrated diagnostic and therapeutic functions show
      exciting potentials towards precision nanomedicine. However, targeted delivery of
      nanotheranostics is hindered by several biological barriers. Here, we report the
      development of a dual size/charge- transformable, Trojan-Horse nanoparticle (pPhD
      NP) for delivery of ultra-small, full active pharmaceutical ingredients (API)
      nanotheranostics with integrated dual-modal imaging and trimodal therapeutic
      functions. pPhD NPs exhibit ideal size and charge for drug transportation. In
      tumour microenvironment, pPhD NPs responsively transform to full API
      nanotheranostics with ultra-small size and higher surface charge, which
      dramatically facilitate the tumour penetration and cell internalisation. pPhD NPs
      enable visualisation of biodistribution by near-infrared fluorescence imaging,
      tumour accumulation and therapeutic effect by magnetic resonance imaging.
      Moreover, the synergistic photothermal-, photodynamic- and chemo-therapies
      achieve a 100% complete cure rate on both subcutaneous and orthotopic oral cancer
      models. This nanoplatform with powerful delivery efficiency and versatile
      theranostic functions shows enormous potentials to improve cancer treatment.

PMID- 30194415
TI  - Knowledge and attitudes toward thirdhand smoke among parents with children under
      3 years in Spain.
AB  - INTRODUCTION: The knowledge and beliefs about what is thirdhand smoke (THS) are
      limited. Our objective is to characterize the knowledge and beliefs about THS in
      parents of children under 3 years old in Spain. METHODS: A cross-sectional study
      (n = 1406 parents) was conducted online in 2017. We collected information about
      the knowledge of THS given later, written information with the definition of THS,
      and asking about beliefs of the effects of THS on children's health. RESULTS: A
      total of 27% of the respondents had heard about THS. We only found significant
      differences among smoking status, being the smokers who declare higher knowledge
      about THS. A total of 86% of the respondents believed that THS is harmful to
      their children with statistically significant differences according to
      educational level, higher among parents with a university degree (ORa = 2.6), and
      according to the previous knowledge on THS (ORa = 2.1). CONCLUSIONS: This is the
      first study in Europe to describe the knowledge and belief of THS. Around 3 out
      of 10 parents have heard about THS and more than 8 out of 10 parents believed
      that THS is harmful to their children. Currently, they were not aware of THS but
      after providing brief information about it, most of them agreed that THS exposure
      is harmful to their children.

PMID- 30194416
TI  - Expression of novel nitrate reductase genes in the harmful alga, Chattonella
      subsalsa.
AB  - Eukaryotic nitrate reductase (NR) catalyzes the first step in nitrate
      assimilation and is regulated transcriptionally in response to external cues and
      intracellular metabolic status. NRs are also regulated post-translationally in
      plants by phosphorylation and binding of 14-3-3 proteins at conserved serine
      residues. 14-3-3 binding motifs have not previously been identified in algal NRs.
      A novel NR (NR2-2/2HbN) with a 2/2 hemoglobin domain was recently described in
      the alga Chattonella subsalsa. Here, a second NR (NR3) in C. subsalsa is
      described with a 14-3-3 binding motif but lacking the Heme-Fe domain found in
      other NRs. Transcriptional regulation of both NRs was examined in C. subsalsa,
      revealing differential gene expression over a diel light cycle, but not under
      constant light. NR2 transcripts increased with a decrease in temperature, while
      NR3 remained unchanged. NR2 and NR3 transcript levels were not inhibited by
      growth on ammonium, suggesting constitutive expression of these genes. Results
      indicate that Chattonella responds to environmental conditions and intracellular
      metabolic status by differentially regulating NR transcription, with potential
      for post-translational regulation of NR3. A survey of algal NRs also revealed the
      presence of 14-3-3 binding motifs in other algal species, indicating the need for
      future research on regulation of algal NRs.

PMID- 30194417
TI  - Deciphering evolutionary dynamics of SWEET genes in diverse plant lineages.
AB  - SWEET/MtN3/saliva genes are prevalent in cellular organisms and play diverse
      roles in plants. These genes are widely considered as evolutionarily conserved
      genes, which is inconsistent with their extensive expansion and functional
      diversity. In this study, SWEET genes were identified from 31 representative
      plant species, and exhibited remarkable expansion and diversification ranging
      from aquatic to land plants. Duplication detection indicated that the sharp
      increase in the number of SWEET genes in higher plants was largely due to tandem
      and segmental duplication, under purifying selection. In addition, phylogeny
      reconstruction of SWEET genes was performed using the maximum-likelihood (ML)
      method; the genes were grouped into four clades, and further classified into 10
      monocot and 11 dicot subfamilies. Furthermore, selection pressure of SWEET genes
      in different subfamilies was investigated via different strategies (classical and
      Bayesian maximum likelihood (Datamonkey/PAML)). The average dN/dS for each group
      were lower than one, indicating purifying selection. Individual positive
      selection sites were detected within 4 of the 21 sub-families by both two
      methods, including two monocot subfamilies in Clade III, harboring five rice
      SWEET homologs characterized to confer resistance to rice bacterial blight
      disease. Finally, we traced evolutionary fate of SWEET genes in clade III for
      functional characterization in future.

PMID- 30194419
TI  - Implementation of an efficient linear-optical quantum router.
AB  - For several decades, scientists have been aware of significant benefits allowing
      quantum information processing technologies to surpass their classical
      counterparts. Recent technological development allows these benefits to be tested
      experimentally and in some cases also implemented in practical devices. So far
      the majority of experimental quantum networks was limited to peer-to-peer
      communications between two parties. Practical implementation of quantum
      communications networks, however, needs to address the problem of scalability to
      serve large numbers of users. Similarly to classical computer networks, their
      quantum counterparts would require routing protocols to direct the signal from
      its source to destination. Devices implementing these routing protocols are
      called quantum routers and have recently been subject of an intense research. In
      this paper, we report on experimental implementation of a linear-optical quantum
      router. Our device allows single-photon polarization-encoded qubits to be routed
      coherently into two spatial output modes depending on the state of two identical
      control qubits. The polarization qubit state of the routed photon is maintained
      during the routing operation. The success probability of our scheme can be
      increased up to 25% making it the most efficient linear-optical quantum router
      developed to this date.

PMID- 30194418
TI  - Correlative microscopy approach for biology using X-ray holography, X-ray
      scanning diffraction and STED microscopy.
AB  - We present a correlative microscopy approach for biology based on holographic X
      ray imaging, X-ray scanning diffraction, and stimulated emission depletion (STED)
      microscopy. All modalities are combined into the same synchrotron endstation. In
      this way, labeled and unlabeled structures in cells are visualized in a
      complementary manner. We map out the fluorescently labeled actin cytoskeleton in
      heart tissue cells and superimpose the data with phase maps from X-ray
      holography. Furthermore, an array of local far-field diffraction patterns is
      recorded in the regime of small-angle X-ray scattering (scanning SAXS), which can
      be interpreted in terms of biomolecular shape and spatial correlations of all
      contributing scattering constituents. We find that principal directions of
      anisotropic diffraction patterns coincide to a certain degree with the actin
      fiber directions and that actin stands out in the phase maps from holographic
      recordings. In situ STED recordings are proposed to formulate models for
      diffraction data based on co-localization constraints.

PMID- 30194420
TI  - T cell microvilli constitute immunological synaptosomes that carry messages to
      antigen-presenting cells.
AB  - Microvilli on T cells have been proposed to survey surfaces of antigen-presenting
      cells (APC) or facilitate adhesion under flow; however, whether they serve
      essential functions during T cell activation remains unclear. Here we show that
      antigen-specific T cells deposit membrane particles derived from microvilli onto
      the surface of cognate antigen-bearing APCs. Microvilli carry T cell receptors
      (TCR) at all stages of T cell activation and are released as large TCR-enriched,
      T cell microvilli particles (TMP) in a process of trogocytosis. These microvilli
      exclusively contain protein arrestin-domain-containing protein 1, which is
      directly involved in membrane budding and, in combination with vacuolar protein
      sorting-associated protein 4, transforms large TMPs into smaller, exosome-sized
      TMPs. Notably, TMPs from CD4+ T cells are enriched with LFA-2/CD2 and various
      cytokines involved in activating dendritic cells. Collectively, these results
      demonstrate that T cell microvilli constitute "immunological synaptosomes" that
      carry T cell messages to APCs.

PMID- 30194421
TI  - Neuronal network maturation differently affects secretory vesicles and
      mitochondria transport in axons.
AB  - Studying intracellular dynamics in neurons is crucial to better understand how
      brain circuits communicate and adapt to environmental changes. In neurons, axonal
      secretory vesicles underlie various functions from growth during development to
      plasticity in the mature brain. Similarly, transport of mitochondria, the power
      plant of the cell, regulates both axonal development and synaptic homeostasis.
      However, because of their submicrometric size and rapid velocities, studying the
      kinetics of these organelles in projecting axons in vivo is technically
      challenging. In parallel, primary neuronal cultures are adapted to study axonal
      transport but they lack the physiological organization of neuronal networks,
      which in turn may bias observations. We previously developed a microfluidic
      platform to reconstruct a physiologically-relevant and functional corticostriatal
      network in vitro that is compatible with high-resolution videorecording of axonal
      trafficking. Here, using this system we report progressive changes in axonal
      transport kinetics of both dense core vesicles and mitochondria that correlate
      with network development and maturation. Interestingly, axonal flow of both types
      of organelles change in opposite directions, with rates increasing for vesicles
      and decreasing for mitochondria. Overall, our observations highlight the need for
      a better spatiotemporal control for the study of intracellular dynamics in order
      to avoid misinterpretations and improve reproducibility.

PMID- 30194422
TI  - The ventromedial prefrontal cortex: a putative locus for trait inattention.

PMID- 30194423
TI  - Are lithium effects dependent on genetic/epigenetic architecture?

PMID- 30194424
TI  - Genetic screen in myeloid cells identifies TNF-alpha autocrine secretion as a
      factor increasing MDSC suppressive activity via Nos2 up-regulation.
AB  - The suppressive microenvironment of tumors remains one of the limiting factors
      for immunotherapies. In tumors, the function of effector T cells can be inhibited
      by cancer cells as well as myeloid cells including tumor associated macrophages
      and myeloid-derived suppressor cells (MDSC). A better understanding of how
      myeloid cells inhibit T cell function will guide the design of therapeutic
      strategies to increase anti-tumor responses. We have previously reported the in
      vitro differentiation of MDSC from immortalized mouse hematopoietic progenitors
      and characterized the impact of retinoic acid and 3-deazaneplanocin A on MDSC
      development and function. We describe here the effect of these compounds on MDSC
      transcriptome and identify genes and pathway affected by the treatment. In order
      to accelerate the investigation of gene function in MDSC suppressive activity, we
      developed protocols for CRISPR/Cas9-mediated gene editing in MDSC. Through
      screening of 217 genes, we found that autocrine secretion of TNF-alpha
      contributes to MDSC immunosuppressive activity through up-regulation of Nos2. The
      approach described here affords the investigation of gene function in myeloid
      cells such as MDSC with unprecedented ease and throughput.

PMID- 30194426
TI  - A Transfer Learning Approach for Microstructure Reconstruction and Structure
      property Predictions.
AB  - Stochastic microstructure reconstruction has become an indispensable part of
      computational materials science, but ongoing developments are specific to
      particular material systems. In this paper, we address this generality problem by
      presenting a transfer learning-based approach for microstructure reconstruction
      and structure-property predictions that is applicable to a wide range of material
      systems. The proposed approach incorporates an encoder-decoder process and
      feature-matching optimization using a deep convolutional network. For
      microstructure reconstruction, model pruning is implemented in order to study the
      correlation between the microstructural features and hierarchical layers within
      the deep convolutional network. Knowledge obtained in model pruning is then
      leveraged in the development of a structure-property predictive model to
      determine the network architecture and initialization conditions. The generality
      of the approach is demonstrated numerically for a wide range of material
      microstructures with geometrical characteristics of varying complexity. Unlike
      previous approaches that only apply to specific material systems or require a
      significant amount of prior knowledge in model selection and hyper-parameter
      tuning, the present approach provides an off-the-shelf solution to handle complex
      microstructures, and has the potential of expediting the discovery of new
      materials.

PMID- 30194425
TI  - Low-dose calcipotriol can elicit wound closure, anti-microbial, and anti
      neoplastic effects in epidermolysis bullosa keratinocytes.
AB  - Recessive dystrophic epidermolysis bullosa (RDEB) patients suffer from chronic
      and repeatedly infected wounds predisposing them to the development of aggressive
      and life-threatening skin cancer in these areas. Vitamin D3 is an often neglected
      but critical factor for wound healing. Intact skin possesses the entire enzymatic
      machinery required to produce active 1-alpha,25-dihydroxyvitamin D3 (calcitriol),
      underscoring its significance to proper skin function. Injury enhances calcitriol
      production, inducing the expression of calcitriol target genes including the
      antimicrobial peptide cathelicidin (hCAP18), an essential component of the innate
      immune system and an important wound healing factor. We found significantly
      reduced hCAP18 expression in a subset of RDEB keratinocytes which could be
      restored by calcipotriol treatment. Reduced scratch closure in RDEB cell
      monolayers was enhanced up to 2-fold by calcipotriol treatment, and the secretome
      of calcipotriol-treated cells additionally showed increased antimicrobial
      activity. Calcipotriol exhibited anti-neoplastic effects, suppressing the
      clonogenicity and proliferation of RDEB tumor cells. The combined wound healing,
      anti-microbial, and anti-neoplastic effects indicate that calcipotriol may
      represent a vital therapeutic option for RDEB patients which we could demonstrate
      in a single-patient observation study.

PMID- 30194427
TI  - Development of a quantitative evaluation system for visuo-motor control in three
      dimensional virtual reality space.
AB  - The process of learning a human's movement and motor control mechanisms by
      watching and mimicking human motions was based on visuo-motor control in three
      dimensional space. However, previous studies regarding the visuo-motor control in
      three dimensional space have focused on analyzing the tracking tasks along one
      dimensional lines or two-dimensional planes using single or multi-joint
      movements. Therefore, in this study, we developed a new system to quantitatively
      evaluate visuo-motor control in three-dimensional space based on virtual reality
      (VR) environment. Our proposed system is designed to analyze circular tracking
      movements on frontal and sagittal planes in VR space with millimeter level
      accuracy. In particular, we compared the circular tracking movements under
      monocular and binocular vision conditions. The results showed that the accuracy
      of circular tracking movements drops approximately 4.5 times in monocular vision
      than that in binocular vision on both frontal and sagittal planes. We also found
      that significant difference can be observed between frontal and sagittal planes
      for only the accuracy of X-axis in both monocular and binocular visions.

PMID- 30194429
TI  - Cryptic CH4 cycling in the sulfate-methane transition of marine sediments
      apparently mediated by ANME-1 archaea.
AB  - Methane in the seabed is mostly oxidized to CO2 with sulfate as the oxidant
      before it reaches the overlying water column. This microbial oxidation takes
      place within the sulfate-methane transition (SMT), a sediment horizon where the
      downward diffusive flux of sulfate encounters an upward flux of methane. Across
      multiple sites in the Baltic Sea, we identified a systematic discrepancy between
      the opposing fluxes, such that more sulfate was consumed than expected from the
      1:1 stoichiometry of methane oxidation with sulfate. The flux discrepancy was
      consistent with an oxidation of buried organic matter within the SMT, as
      corroborated by stable carbon isotope budgets. Detailed radiotracer experiments
      showed that up to 60% of the organic matter oxidation within the SMT first
      produced methane, which was concurrently oxidized to CO2 by sulfate reduction.
      This previously unrecognized "cryptic" methane cycling in the SMT is not
      discernible from geochemical profiles due to overall net methane consumption.
      Sedimentary gene pools suggested that nearly all potential methanogens within and
      beneath the SMT belonged to ANME-1 archaea, which are typically associated with
      anaerobic methane oxidation. Analysis of a metagenome-assembled genome suggests
      that predominant ANME-1 do indeed have the enzymatic potential to catalyze both
      methane production and consumption.

PMID- 30194428
TI  - Author Correction: Yolk sac macrophage progenitors traffic to the embryo during
      defined stages of development.
AB  - This article contains errors in Figs. 5 and 6, for which we apologize. In Fig.
      5f, the image 'E12.5 tail' was inadvertently replaced with a duplicate of the
      image 'E12.5 trunk' from the same panel. In Figure 6d, the image 'E9.5/OH-TAM
      E8.5, embryo' was inadvertently replaced with a duplicate of the image 'E10.5/ OH
      TAM E8.5, embryo' from Fig. 6b. The corrected versions of these figures appear in
      the Author Correction associated with this Article.

PMID- 30194430
TI  - Consistent microbial dynamics and functional community patterns derived from
      first principles.
AB  - Microbial communities are key engines that drive earth's biogeochemical cycles.
      However, existing ecosystem models have only limited ability to predict microbial
      dynamics and require the calibration of multiple population-specific empirical
      equations. In contrast, we build on a new kinetic "Microbial Transition State"
      (MTS) theory of growth derived from first principles. We show how the theory
      coupled to simple mass and energy balance calculations provides a framework with
      intrinsically important qualitative properties to model microbial community
      dynamics. We first show how the theory can simultaneously account for the
      influence of all the resources needed for growth (electron donor, acceptor, and
      nutrients) while still producing consistent dynamics that fulfill the Liebig rule
      of a single limiting substrate. We also show consistent patterns of energy
      dependent microbial successions in mixed culture without the need for calibration
      of population-specific parameters. We then show how this approach can be used to
      model a simplified activated sludge community. To this end, we compare MTS
      derived dynamics with those of a widely used activated sludge model and show that
      similar growth yields and overall dynamics can be obtained using two parameters
      instead of twelve. This new kinetic theory of growth grounded by a set of generic
      physical principles parsimoniously gives rise to consistent microbial population
      and community dynamics, thereby paving the way for the development of a new class
      of more predictive microbial ecosystem models.

PMID- 30194431
TI  - Solubility-mediated sustained release enabling nitrate additive in carbonate
      electrolytes for stable lithium metal anode.
AB  - The physiochemical properties of the solid-electrolyte interphase, primarily
      governed by electrolyte composition, have a profound impact on the
      electrochemical cycling of metallic lithium. Herein, we discover that the effect
      of nitrate anions on regulating lithium deposition previously known in ether
      based electrolytes can be extended to carbonate-based systems, which dramatically
      alters the nuclei from dendritic to spherical, albeit extremely limited
      solubility. This is attributed to the preferential reduction of nitrate during
      solid-electrolyte interphase formation, and the mechanisms behind which are
      investigated based on the structure, ion-transport properties, and charge
      transfer kinetics of the modified interfacial environment. To overcome the
      solubility barrier, a solubility-mediated sustained-release methodology is
      introduced, in which nitrate nanoparticles are encapsulated in porous polymer gel
      and can be steadily dissolved during battery operation to maintain a high
      concentration at the electroplating front. As such, effective dendrite
      suppression and remarkably enhanced cycling stability are achieved in corrosive
      carbonate electrolytes.

PMID- 30194432
TI  - Barcoding of Chrysomelidae of Euro-Mediterranean area: efficiency and problematic
      species.
AB  - Leaf beetles (Coleoptera: Chrysomelidae), with more than 37,000 species worldwide
      and about 2,300 in the Euro-Mediterranean region, are an ecological and
      economical relevant family, making their molecular identification of interest
      also in agriculture. This study, part of the Mediterranean Chrysomelidae
      Barcoding project (www.c-bar.org), aims to: (i) develop a reference Cytochrome c
      oxidase I (COI) library for the molecular identification of the Euro
      Mediterranean Chrysomelidae; (ii) test the efficiency of DNA barcoding for leaf
      beetles identification; (iii) develop and compare optimal thresholds for distance
      based identifications estimated at family and subfamily level, minimizing false
      positives and false negatives. Within this study, 889 COI nucleotide sequences of
      261 species were provided; after the inclusion of information from other sources,
      a dataset of 7,237 sequences (542 species) was analysed. The average intra
      interspecific distances were in the range of those recorded for Coleoptera: 1.6
      24%. The estimated barcoding efficiency (~94%) confirmed the usefulness of this
      tool for Chrysomelidae identification. The few cases of failure were recorded for
      closely related species (e.g., Cryptocephalus marginellus superspecies,
      Cryptocephalus violaceus - Cryptocephalus duplicatus and some Altica species),
      even with morphologically different species sharing the same COI haplotype.
      Different optimal thresholds were achieved for the tested taxonomic levels,
      confirming that group-specific thresholds significantly improve molecular
      identifications.

PMID- 30194433
TI  - Comparison of the Rat and Human Dorsal Root Ganglion Proteome.
AB  - Dorsal root ganglion (DRG) are a key tissue in the nervous system that have a
      role in neurological disease, particularly pain. Despite the importance of this
      tissue, the proteome of DRG is poorly understood, and it is unknown whether the
      proteome varies between organisms or different DRG along the spine. Therefore, we
      profiled the proteome of human and rat DRG. We identified 5,245 proteins in human
      DRG and 4959 proteins in rat DRG. Across species the proteome is largely
      conserved with some notable differences. While the most abundant proteins in both
      rat and human DRG played a role in extracellular functions and myelin sheeth,
      proteins detected only in humans mapped to roles in immune function whereas those
      detected only in rat mapped to roles in localization and transport. The DRG
      proteome between human T11 and L2 vertebrae was nearly identical indicating DRG
      from different vertebrae are representative of one another. Finally, we asked if
      this data could be used to enhance translatability by identifying mechanisms that
      modulate cellular phenotypes representative of pain in different species. Based
      on our data we tested and discovered that MAP4K4 inhibitor treatment increased
      neurite outgrowth in rat DRG as in human SH-SY5Y cells.

PMID- 30194434
TI  - High-throughput chromatin accessibility profiling at single-cell resolution.
AB  - Here we develop a high-throughput single-cell ATAC-seq (assay for transposition
      of accessible chromatin) method to measure physical access to DNA in whole cells.
      Our approach integrates fluorescence imaging and addressable reagent deposition
      across a massively parallel (5184) nano-well array, yielding a nearly 20-fold
      improvement in throughput (up to ~1800 cells/chip, 4-5 h on-chip processing time)
      and library preparation cost (~81c per cell) compared to prior microfluidic
      implementations. We apply this method to measure regulatory variation in
      peripheral blood mononuclear cells (PBMCs) and show robust, de novo clustering of
      single cells by hematopoietic cell type.

PMID- 30194435
TI  - Accelerated phosphorus recovery from aqueous solution onto decorated sewage
      sludge carbon.
AB  - In search of efficient phosphorus resource recovery and pollution remediation
      should be highly concerned due to the view of phosphorus nonrenewable and
      eutrophication. This work presented a new insight into conversion of sewage
      sludge into favorable carbonaceous adsorbent for accelerated removing and
      recovering phosphorus from aqueous solution, what addressed the issues of
      phosphorus recovery and pollution remediation as well as sludge disposal. Ca and
      water hyacinth were evolved to decorate sludge derived carbon. Effect of mass
      ratio of sludge, water hyacinth and calcium carbonate on the morphologies and
      adsorption kinetics was investigated. The adsorbents (SW-Ca-112) resulted from
      sludge in the presence of water hyacinth and CaCO3 in a mass ratio of 1:1:2 had
      the highest adsorption capacity of 49.50 mg/g P and adsorption rate. Decoration
      of Ca favored adsorption ability and the presence of water hyacinth accelerated
      the adsorption rate due to the enhanced porosity. Formation of acicular
      Ca5(PO4)3OH nanoparticles contributed to the favorable adsorption process. Thus,
      the contribution of decorated Ca and water hyacinth to the adsorption ability and
      rate to phosphorus was understand, providing important information on resource
      utilization of sewage sludge as efficient adsorbent for immobilizing phosphorus
      from aqueous solution.

PMID- 30194436
TI  - Cascade biotransformation of dehydroepiandrosterone (DHEA) by Beauveria species.
AB  - Beauveria bassiana is an entomopathogenic fungus used as a biological control
      agent. It is a well-known biocatalyst for the transformation of steroid
      compounds. Hydroxylations at the 7alpha or 11alpha position and oxidation to D
      homo lactones are described in the literature. In our study, we examined the
      diversity of metabolism of five different B. bassiana strains and compared them
      to already known pathways. According to the literature, 7alpha and 11alpha
      hydroxy derivatives as well as 3beta,11alpha-dihydroxy-17a-oxa-D-homo-androst-5
      en-17-one have been observed. Here we describe new DHEA metabolic pathways and
      two products not described before: 3beta-hydroxy-17a-oxa-D-homo-androst-5-en-7,17
      dione and 3beta,11alpha-dihydroxyandrost-5-en-7,17-dione. We also used for the
      first time another species from this genus, Beauveria caledonica, for steroid
      transformation. DHEA was hydroxylated at the 7alpha, 7beta and 11alpha positions
      and then reactions of oxidation and reduction leading to 3beta,11alpha
      dihydroxyandrost-5-en-7,17-dione were observed. All tested strains from the
      Beauveria genus effectively transformed the steroid substrate using several
      different enzymes, resulting in cascade transformation.

PMID- 30194438
TI  - What's new under the Sun for ICIs?

PMID- 30194437
TI  - Survival predictors in elderly patients with acute respiratory distress syndrome:
      a prospective observational cohort study.
AB  - Acute respiratory distress syndrome (ARDS) has a high mortality rate in intensive
      care units (ICU). The elderly patients remain to be increased of ICU patients.
      The aim is to investigate the survival predictors of elderly patients with ARDS.
      We reported a prospective observational cohort research, including the patients
      with ARDS between October 2012 and May 2015. Demographic, comorbidities,
      severity, lung mechanics, laboratory data and survival outcomes were analyzed. A
      total of 463 patients with ARDS were >=65 years old were enrolled and analyzed.
      Multivariate logistic regression analysis identified Charlson comorbidity index
      (CCI) [odds ratio (OR) 1.111, 95% CI 1.010-1.222, p = 0.031], Sequential Organ
      Failure Assessment (SOFA) score (OR 1.127, 95% CI 1.054-1.206, p < 0.001) and
      peak inspiratory pressure (PIP) (OR 1.061, 95% CI 1.024-1.099, p = 0.001) which
      were independently associated with hospital mortality. Regarding the subgroups
      patients as 65-74 years old, 75-84 years old and >=85 years old, the baseline
      characteristics were not significant difference and the hospital mortality rates
      were also not significant difference. In conclusion, CCI, SOFA score and PIP were
      identified as survival predictors in elderly patient with ARDS. Assessing
      comorbidities with CCI is essential in predicting the survival for elderly
      patients with ARDS.

PMID- 30194439
TI  - Dual action of L-Lactate on the activity of NR2B-containing NMDA receptors: from
      potentiation to neuroprotection.
AB  - L-Lactate is a positive modulator of NMDAR-mediated signaling resulting in
      plasticity gene induction and memory consolidation. However, L-Lactate is also
      able to protect neurons against excito-toxic NMDAR activity, an indication of a
      mitigating action of L-Lactate on NMDA signaling. In this study, we provide
      experimental evidence that resolves this apparent paradox. Transient co
      application of glutamate/glycine (1 MUM/100 MUM; 2 min) in primary cultures of
      mouse cortical neurons triggers a NMDA-dependent Ca2+ signal positively modulated
      by L-Lactate (10 mM) or DTT (1 mM) but decreased by Pyruvate (10 mM). This L
      Lactate and DTT-induced potentiation is blocked by Ifenprodil (2 MUM), a specific
      blocker of NMDARs containing NR2B sub-units. In contrast, co-application of
      glutamate/glycine (1 mM/100 MUM; 2 min) elicits a NMDAR-dependent excitotoxic
      death in 49% of neurons. L-Lactate and Pyruvate significantly reduce this rate of
      cell death processes (respectively to 23% and 9%) while DTT has no effect (54% of
      neuronal death). This L-Lactate-induced neuroprotection is blocked by
      carbenoxolone and glibenclamide, respectively blockers of pannexins and KATP. In
      conclusion, our results show that L-Lactate is involved in two distinct and
      independent pathways defined as NMDAR-mediated potentiation pathway (or NADH
      pathway) and a neuroprotective pathway (or Pyruvate/ATP pathway), the prevalence
      of each one depending on the strength of the glutamatergic stimulus.

PMID- 30194440
TI  - Canine morbillivirus (canine distemper virus) with concomitant canine adenovirus,
      canine parvovirus-2, and Neospora caninum in puppies: a retrospective
      immunohistochemical study.
AB  - A retrospective immunohistochemical study was designed to investigate the
      frequency of concomitant traditional infectious disease pathogens in puppies that
      died suddenly and review the aspects of associated pathogenesis. Fifteen puppies
      were evaluated; the pathology reports and histopathologic slides of these animals
      were reviewed to determine the pattern of histopathologic lesions. The
      intralesional identification of antigens of canine (distemper) morbillivirus
      (CDV), canine adenovirus-1 and -2 (CAdV-1 and -2), canine parvovirus-2 (CPV-2),
      Toxoplasma gondii, and Neospora caninum was evaluated by IHC within the
      histopathologic patterns observed. All puppies contained CDV nucleic acid by
      molecular testing. The most frequent histopathologic patterns were intestinal
      crypt necrosis (n = 8), white matter cerebellar demyelination (n = 7),
      necrohaemorrhagic hepatitis (n = 7), interstitial pneumonia (n = 7), and
      gallbladder oedema (n = 5). All puppies contained intralesional antigens of CDV
      in multiple tissues resulting in singular (n = 3), and concomitant dual (n = 3),
      triple (n = 5) and quadruple (n = 4) infections by CAdV-1, and -2, CPV-2, and N.
      caninum; T. gondii was not identified. Concomitant infections by CDV was observed
      with N. caninum (100%; 1/1), CPV-2 (100%; 8/8), CAdV-1 (100%; 8/8), and CAdV-2
      (100%; 8/8). Intralesional antigens of CDV and not CAdV-1 were identified in
      cases of gallbladder oedema. The "blue eye" phenomenon was histologically
      characterized by corneal oedema and degenerative lesions to the corneal
      epithelium, without inflammatory reactions.

PMID- 30194441
TI  - USP4 positively regulates RLR-induced NF-kappaB activation by targeting TRAF6 for
      K48-linked deubiquitination and inhibits enterovirus 71 replication.
AB  - Retinoic acid-inducible gene I-like receptor (RLR) is one of the most important
      pattern recognition receptors of the innate immune system that detects positive
      and/or negative stranded RNA viruses. Subsequently, it stimulates downstream
      transcription of interferon regulatory factor 3 (IRF3) and nuclear factor kappaB
      (NF-kappaB) inducing the production of interferons (IFNs) and inflammatory
      cytokines. Tumour necrosis factor receptor associated factor 6 (TRAF6) is a key
      protein involved in the RLR-mediated antiviral signalling pathway, recruiting
      additional proteins to form a multiprotein complex capable of activating the NF
      kappaB inflammatory pathway. Despite TRAF6 playing an important role in
      regulating host immunity and viral infection, the deubiquitination of TRAF6
      induced by viral infection remains elusive. In this study, we found that
      enterovirus 71 (EV71) infection attenuated the expression of Ubiquitin-specific
      protease 4 (USP4) in vitro and in vivo, while overexpression of USP4
      significantly suppressed EV71 replication. Furthermore, it was found that EV71
      infection reduced the RLR signalling pathway and enhanced the degradation of
      TRAF6. USP4 was also found to interact with TRAF6 and positively regulate the RLR
      induced NF-kappaB signalling pathway, inhibiting the replication of EV71.
      Therefore, as a novel positive regulator of TRAF6, USP4 plays an essential role
      in EV71 infection by deubiquitinating K48-linked ubiquitin chains.

PMID- 30194442
TI  - Novel analgesic omega-conotoxins from the vermivorous cone snail Conus moncuri
      provide new insights into the evolution of conopeptides.
AB  - Cone snails are a diverse group of predatory marine invertebrates that deploy
      remarkably complex venoms to rapidly paralyse worm, mollusc or fish prey. omega
      Conotoxins are neurotoxic peptides from cone snail venoms that inhibit Cav2.2
      voltage-gated calcium channel, demonstrating potential for pain management via
      intrathecal (IT) administration. Here, we isolated and characterized two novel
      omega-conotoxins, MoVIA and MoVIB from Conus moncuri, the first to be identified
      in vermivorous (worm-hunting) cone snails. MoVIA and MoVIB potently inhibited
      human Cav2.2 in fluorimetric assays and rat Cav2.2 in patch clamp studies, and
      both potently displaced radiolabeled omega-conotoxin GVIA (125I-GVIA) from human
      SH-SY5Y cells and fish brain membranes (IC50 2-9 pM). Intriguingly, an arginine
      at position 13 in MoVIA and MoVIB replaced the functionally critical tyrosine
      found in piscivorous omega-conotoxins. To investigate its role, we synthesized
      MoVIB-[R13Y] and MVIIA-[Y13R]. Interestingly, MVIIA-[Y13R] completely lost Cav2.2
      activity and MoVIB-[R13Y] had reduced activity, indicating that Arg at position
      13 was preferred in these vermivorous omega-conotoxins whereas tyrosine 13 is
      preferred in piscivorous omega-conotoxins. MoVIB reversed pain behavior in a rat
      neuropathic pain model, confirming that vermivorous cone snails are a new source
      of analgesic omega-conotoxins. Given vermivorous cone snails are ancestral to
      piscivorous species, our findings support the repurposing of defensive venom
      peptides in the evolution of piscivorous Conidae.

PMID- 30194443
TI  - Sensing phases of water via nitrogen-vacancy centres in diamond.
AB  - Ultra-thin layers of liquids on a surface behave differently from bulk liquids
      due to liquid-surface interactions. Some examples are significant changes in
      diffusion properties and the temperature at which the liquid-solid phase
      transition takes place. Indeed, molecular dynamics simulations suggest that thin
      layers of water on a diamond surface may remain solid even well above room
      temperature. However, because of the small volumes that are involved, it is
      exceedingly difficult to examine these phenomena experimentally with current
      technologies. In this context, shallow NV centres promise a highly sensitive tool
      for the investigation of magnetic signals emanating from liquids and solids that
      are deposited on the surface of a diamond. Moreover, NV centres are non-invasive
      sensors with extraordinary performance even at room-temperature. To that end, we
      present here a theoretical work, complemented with numerical evidence based on
      bosonization techniques, that predicts the measurable signal from a single NV
      centre when interacting with large spin baths in different configurations. In
      fact, by means of continuous dynamical decoupling, the polarization exchange
      between a single NV centre and the hydrogen nuclear spins from the water
      molecules is enhanced, leading to differences in the coherent dynamics of the NV
      centre that are interpreted as an unambiguous trace of the molecular structure.
      We therefore propose single NV centres as sensors capable to resolve structural
      water features at the nanoscale and even sensitive to phase transitions.

PMID- 30194444
TI  - Publication pressure and scientific misconduct: why we need more open governance.

PMID- 30194445
TI  - High abundances of the nuisance raphidophyte Gonyostomum semen in brown water
      lakes are associated with high concentrations of iron.
AB  - Algal blooms occur frequently in lakes and oceans and the causes and consequences
      of those are often studied. In this study, we focus on a less well known type of
      algal bloom by the freshwater raphidophyte Gonyostomum semen. This species'
      abundance and occurrence is increasing, especially in brown water lakes, the most
      abundant lake type in the boreal zone. The aim of the study was to investigate
      which environmental factors are associated with G. semen by statistical
      evaluation of field data of 95 Swedish lakes over five years. Although we found
      G. semen to be associated with dark waters it was, contrary to our expectations,
      mainly high concentrations of iron, and only to a lesser extent high TOC (total
      organic carbon) concentrations, that were associated with blooms of G. semen. In
      addition, high phosphorus concentrations and low pH also appear to facilitate G.
      semen blooms. We suggest that browning of lakes caused by increased iron
      concentrations may decrease net heterotrophy by fostering heavy algal blooms,
      i.e. the opposite to commonly assumed effects of increased DOM (dissolved organic
      matter).

PMID- 30194448
TI  - Exploring human gastric cancers through organoid culture.

PMID- 30194446
TI  - Arthroscopic near infrared spectroscopy enables simultaneous quantitative
      evaluation of articular cartilage and subchondral bone in vivo.
AB  - Arthroscopic assessment of articular tissues is highly subjective and poorly
      reproducible. To ensure optimal patient care, quantitative techniques (e.g., near
      infrared spectroscopy (NIRS)) could substantially enhance arthroscopic diagnosis
      of initial signs of post-traumatic osteoarthritis (PTOA). Here, we demonstrate,
      for the first time, the potential of arthroscopic NIRS to simultaneously monitor
      progressive degeneration of cartilage and subchondral bone in vivo in Shetland
      ponies undergoing different experimental cartilage repair procedures.
      Osteochondral tissues adjacent to the repair sites were evaluated using an
      arthroscopic NIRS probe and significant (p < 0.05) degenerative changes were
      observed in the tissue properties when compared with tissues from healthy joints.
      Artificial neural networks (ANN) enabled reliable (rho = 0.63-0.87, NMRSE = 8.5
      17.2%, RPIQ = 1.93-3.03) estimation of articular cartilage biomechanical
      properties, subchondral bone plate thickness and bone mineral density (BMD), and
      subchondral trabecular bone thickness, bone volume fraction (BV), BMD, and
      structure model index (SMI) from in vitro spectral data. The trained ANNs also
      reliably predicted the properties of an independent in vitro test group (rho =
      0.54-0.91, NMRSE = 5.9-17.6%, RPIQ = 1.68-3.36). However, predictions based on
      arthroscopic NIR spectra were less reliable (rho = 0.27-0.74, NMRSE = 14.5-24.0%,
      RPIQ = 1.35-1.70), possibly due to errors introduced during arthroscopic spectral
      acquisition. Adaptation of NIRS could address the limitations of conventional
      arthroscopy through quantitative assessment of lesion severity and extent,
      thereby enhancing detection of initial signs of PTOA. This would be of high
      clinical significance, for example, when conducting orthopaedic repair surgeries.

PMID- 30194447
TI  - Maximum blink interval is associated with tear film breakup time: A new simple,
      screening test for dry eye disease.
AB  - The prevalence of dry eye disease (DED) is increasing worldwide, and its
      diagnosis often needs dedicated reagents and machines. We investigated the
      usefulness of maximum blink interval (MBI) (the length of time that participants
      could keep their eyes open) in screening for DED. This cross-sectional study
      included 292 patients (194 with DED and 98 without DED) recruited between
      September 2016 and September 2017. We compared the MBI between patients with and
      without DED; examined correlations between MBI and other clinical features of
      DED, including subjective symptoms (Dry Eye-Related Quality-of-Life Score), tear
      film breakup time (TFBUT), cornea fluorescence score (CFS), and Schirmer test I
      value; and determined the optimal cutoff value of MBI to suspect DED using a
      receiver operating characteristic (ROC) analysis. The MBI was significantly
      shortened in DED group compared to the non-DED group (10.0 +/- 9.1 vs. 24.3 +/-
      38.2 seconds, p < 0.001). TFBUT was strongly positively correlated with MBI (r =
      0.464), whereas CFS was negatively correlated with MBI (r = -0.273). The area
      under the ROC curve was 0.677, and the optimal MBI cutoff value was 12.4 seconds,
      providing a sensitivity of 82.5% and specificity of 51.0% to suspect DED. In
      conclusion, MBI may be a simple, useful test for screening DED.

PMID- 30194449
TI  - Arginine refolds, stabilizes, and restores function of mutant pVHL proteins in
      animal model of the VHL cancer syndrome.
AB  - The von Hippel-Lindau (VHL) syndrome is a rare inherited cancer, caused by
      mutations in the VHL gene, many of which render the VHL protein (pVHL) unstable.
      pVHL is a tumor-suppressor protein implicated in a variety of cellular processes,
      most notably in response to changes in oxygen availability, due to its role as
      part of an E3-ligase complex which targets the hypoxia-inducible factor (HIF) for
      degradation. Previously we reported, using in silico and in vitro analyses, that
      common oncogenic VHL mutations render pVHL less stable than the wild-type
      protein, distort its core domain and as a result reduce the ability of the
      protein to bind its target HIF-1alpha. Among various chemical chaperones tested,
      arginine was the most effective in refolding mutant of pVHL. Here we examined the
      consequences of administering L- or D-arginine to a Drosophila VHL model and to
      human renal carcinoma cells, both expressing misfolded versions of human pVHL.
      Arginine treatment increased pVHL solubility in both models and increased the
      half-life of the mutant pVHL proteins in the cell culture. In both models, L- as
      well as D-arginine enhanced the ability of wild-type pVHL and certain misfolded
      mutant versions of pVHL to bind ODD, the HIF-derived target peptide, reflecting
      restoration of pVHL function. Moreover, continuous feeding of Drosophila
      expressing misfolded versions of pVHL either L- or D-arginine rich diet rescued
      their lethal phenotype. Collectively, these in vivo results suggest that arginine
      supplementation should be examined as a potential novel treatment for VHL cancer
      syndrome.

PMID- 30194450
TI  - VEGF165b, a splice variant of VEGF-A, promotes lung tumor progression and escape
      from anti-angiogenic therapies through a beta1 integrin/VEGFR autocrine loop.
AB  - Vascular endothelial growth factor-A (VEGF-A) is highly subjected to alternative
      pre-mRNA splicing that generates several splice variants. The VEGFxxx and
      VEGFxxxb families encode splice variants of VEGF-A that differ only at the level
      of six amino acids in their C-terminal part. The expression level of VEGFxxx
      splice variants and their function as pro-angiogenic factors during tumor neo
      angiogenesis have been well-described. The role of VEGFxxxb isoforms is less well
      known, but they have been shown to inhibit VEGFxxx-mediated angiogenesis, while
      being partial or weak activators of VEGFR receptors in endothelial cells. On the
      opposite, their role on tumor cells expressing VEGFRs at their surface remains
      largely unknown. In this study, we find elevated levels of VEGF165b, the main
      VEGFxxxb isoform, in 36% of non-small cell lung carcinoma (NSCLC), mainly lung
      adenocarcinoma (46%), and show that a high VEGF165b/VEGF165 ratio correlates with
      the presence of lymph node metastases. At the molecular level, we demonstrate
      that VEGF165b stimulates proliferation and invasiveness of two lung tumor cell
      lines through a VEGFR/beta1 integrin loop. We further provide evidence that the
      isoform-specific knockdown of VEGF165b reduces tumor growth, demonstrating a
      tumor-promoting autocrine role for VEGF165b in lung cancer cells. Importantly, we
      show that bevacizumab, an anti-angiogenic compound used for the treatment of lung
      adenocarcinoma patients, increases the expression of VEGF165b and activates the
      invasive VEGFR/beta1 integrin loop. Overall, these data highlight an unexpected
      role of the VEGF165b splice variant in the progression of lung tumors and their
      response to anti-angiogenic therapies.

PMID- 30194451
TI  - A molecular portrait of epithelial-mesenchymal plasticity in prostate cancer
      associated with clinical outcome.
AB  - The propensity of cancer cells to transition between epithelial and mesenchymal
      phenotypic states via the epithelial-mesenchymal transition (EMT) program can
      regulate metastatic processes, cancer progression, and treatment resistance.
      Transcriptional investigations using reversible models of EMT, revealed the
      mesenchymal-to-epithelial reverting transition (MErT) to be enriched in clinical
      samples of metastatic castrate resistant prostate cancer (mCRPC). From this
      enrichment, a metastasis-derived gene signature was identified that predicted
      more rapid cancer relapse and reduced survival across multiple human carcinoma
      types. Additionally, the transcriptional profile of MErT is not a simple mirror
      image of EMT as tumour cells retain a transcriptional "memory" following a
      reversible EMT. This memory was also enriched in mCRPC samples. Cumulatively, our
      studies reveal the transcriptional profile of epithelial-mesenchymal plasticity
      and highlight the unique transcriptional properties of MErT. Furthermore, our
      findings provide evidence to support the association of epithelial plasticity
      with poor clinical outcomes in multiple human carcinoma types.

PMID- 30194452
TI  - Delivering better results for patients through core outcomes, measuring evidence
      and patient participation.
AB  - Nasal obstruction is one of the most frequent and bothersome symptoms in
      rhinosinal disease. Although we are able to measure nasal airflow, the
      correlation between the feeling of nasal obstruction and objective measurements
      has been shown to be average at most. A significant proportion of the European
      population has a more or less deviated nasal septum and deviated septa have
      received a lot of attention from otorhinolaryngologists. In sharp contrast is the
      amount of hard evidence concerning septoplasty with or without turbinate surgery.

PMID- 30194453
TI  - An assessment of retention behavior for gold nanorods in asymmetrical flow field
      flow fractionation.
AB  - Applications of asymmetrical flow field-flow fractionation (AF4) continue to
      expand rapidly in the fields of nanotechnology and biotechnology. In particular,
      AF4 has proven valuable for the separation and analysis of particles,
      biomolecular species (e.g., proteins, bacteria) and polymers (natural and
      synthetic), ranging in size from a few nanometers to several micrometers. The
      separation of non-spheroidal structures (e.g., rods, tubes, etc.) with primary
      dimensions in the nanometer regime, is a particularly challenging application
      deserving of greater study and consideration. The goal of the present study was
      to advance current understanding of the mechanism of separation of rod-like nano
      objects in the AF4 channel. To achieve this, we have systematically investigated
      a series of commercially available cetyltrimethylammonium bromide stabilized gold
      nanorods (AuNRs), with aspect ratios from 1.7 to 10. Results show clearly that
      the retention time is principally dependent on the translational diffusion
      coefficient of the AuNRs. Equations used to calculate translational and
      rotational diffusion coefficients (cylinder and prolate ellipsoid models) yield
      similarly good fits to experimental data. Well characterized gold nanorods
      (length and diameter by transmission electron microscopy) can be used as
      calibrants for AF4 measurements allowing one to determine the aspect ratio of
      nanorod samples based on their retention times. Graphical abstract ?.

PMID- 30194454
TI  - Adaptation and improvement of an elemental mapping method for lithium ion battery
      electrodes and separators by means of laser ablation-inductively coupled plasma
      mass spectrometry.
AB  - In this study, laser ablation-inductively coupled plasma-mass spectrometry (LA
      ICP-MS) was applied to previously aged carbonaceous anodes from lithium ion
      batteries (LIBs). The electrodes were treated by cyclic aging in a lithium ion
      cell set-up with LiNi0.5Mn1,5O4 (LNMO) cathodes and hard carbon (HC)/mesocarbon
      microbead (MCMB) anodes. An inhomogeneous transition metal deposition pattern
      could be induced by replacing the spacer in a standard coin cell set-up with a
      washer. The inhomogeneity pattern matched the dimension of the washer depicted by
      the hole in the center. These transition metal (TM) patterns were used to
      optimize higher lateral scanning speeds and frequencies on the spatial resolution
      of the mapping experiments using LA-ICP-MS. Higher scanning speeds had an
      observable influence on the resolution of the obtained image and an overall
      saving of 60% with regard to time and gas consumption could be achieved.
      Additionally, the optimized method was applied to the cathode and separator in
      order to visualize the distribution and deposition pattern, respectively.

PMID- 30194455
TI  - Gender does not make a difference in "composite psoriatic disease activity index
      (CPDAI)" in patients with psoriatic arthritis.
AB  - The aim of the study was to investigate the relationship of CPDAI with other
      follow-up parameters and to evaluate gender differences in measures in psoriatic
      arthritis (PsA) patients. This cross-sectional study included patients with PsA
      followed up at a rheumatology outpatient clinic. Disease activity was assessed
      using CPDAI, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Visual
      Analog Scale (VASglobal) and Disease Activity Score (DAS28). Erythrocyte
      sedimentation rate (ESR) and C-reactive protein (CRP) levels were measured. The
      Psoriasis Area and Severity Index (PASI) was used to measure of severity of
      psoriasis. Bath Ankylosing Spondylitis Functional (BASFI) and Metrology Indexes
      (BASMI), Health Assessment Questionnaire (HAQ), AS Quality of Life (ASQoL) and
      Dermatology Life Quality Index (DLQI) were evaluated. There were 117 patients
      with PsA (78 female) who fulfilled the Classification Criteria for Psoriatic
      Arthritis. Their mean CPDAI score was 3.67 (+/- 2.46). The CPDAI was positively
      correlated with tender/swollen joint counts, dactylitis and enthesitis. There was
      strong positive correlation between CPDAI and BASDAI, DAS28 and VASglobal, but no
      correlation found between the CPDAI and ESR, CRP and BASMI. Mean CPDAI scores
      were similar in females and males. Female patients were found to have worse
      subjective scores including BASDAI, VASglobal, BASFI, HAQ and ASQoL than males (p
      < 0.05). However, objective disease parameters such as ESR, CRP, tender/swollen
      joint counts, DAS28 and BASMI were similar in both gender groups. This study
      confirmed that CPDAI, a compound scale to assess disease activity in PsA, was
      well correlated with other disease activity measurements. Although subjective
      disease scores were higher in female patients, CPDAI was not affected by gender.

PMID- 30194456
TI  - Development of perceived pharmacological deficits of medical students and alumni
      supports claim for continuous and more application-oriented education.
AB  - Medical students' prescribing competencies are insufficient. So far, surveys
      focused on final-year students. Knowledge and confidence seem important, but
      their development during medical studies are unclear. This study investigated
      whether students perceived deficits in pharmacological knowledge change during
      medical studies. Alumni were included to look for changes occurring after
      graduation. Medical students at different stages of their studies were invited to
      fill in paper-and-pencil (6th-, 8th-, 9th- and 10th-term students) or online
      questionnaires (final-year students and alumni) regarding their self-assessed
      deficits in pharmacology. Questionnaires have been developed based on previous
      interviews with 10th-term students. We differentiated between declarative and
      application-oriented knowledge. In total, data from 816 participants could be
      analysed. Self-assessment regarding declarative knowledge changed during medical
      studies, being more sceptical in terms without pharmacology courses. Of note,
      self-assessment of application-oriented knowledge remained constantly low
      throughout, although our pharmacology courses use problem-based learning. Tenth
      term students were most sceptical, perhaps influenced by an obligatory,
      formative, simulation-based, 1-week course, preparing students for their final
      practical year. Compared to students, alumni were significantly less sceptical
      regarding application-oriented knowledge. Students' self-assessment of deficits
      in pharmacological knowledge changes throughout their studies, presumably in
      association with pharmacology courses. Overall, students are rather sceptical,
      especially with regard to application-oriented knowledge. Our data further
      substantiate the European Association for Clinical Pharmacology and Therapeutics
      (EACPT) recommendations to improve pharmacology education throughout the entire
      medical curriculum, e.g. by providing more training in simulated and clinical
      environments.

PMID- 30194457
TI  - Thulium laser enucleation versus thulium laser resection of the prostate for
      prevention of bladder neck contracture in a small prostate: a prospective
      randomized trial.
AB  - PURPOSE: To compare the safety and efficacy of thulium laser enucleation of the
      prostate (ThuLEP) versus thulium laser resection of the prostate (TmLRP) in small
      prostates (<= 30 g) and to test the validity of ThuLEP for bladder neck
      contracture (BNC). METHODS: A total of 115 patients with benign prostatic
      hyperplasia (BPH) (prostate size <= 30 g) were randomly assigned to ThuLEP (n =
      56) or TmLRP (n = 59). All patients were evaluated preoperatively and at 1, 3, 6,
      and 12 months after surgery. Baseline characteristics of the patients,
      perioperative data, postoperative outcomes and complications were assessed.
      RESULTS: Comparisons of the baseline and perioperative data demonstrated no
      significant differences between the ThuLEP and TmLRP groups. Significant
      improvement was noted in the International Prostate Symptom Score, quality of
      life, maximal urinary flow rate (Qmax) and post-void residual volume (PVR) in
      both groups at the 12-month follow-up, and assessment showed no differences in
      these parameters between the two groups. The TmLRP group showed a significantly
      higher rate (13.6%) of BNC than the ThuLEP group (1.8%; P = 0.045). There were no
      significant differences in other complications between the two groups (P > 0.05).
      CONCLUSIONS: ThuLEP and TmLRP are both safe and efficient procedures for the
      treatment of patients with small prostate volume, while ThuLEP can significantly
      reduce the risk of BNC in patients with a small prostate because the procedure
      enucleates adenomas without thermal damage to the bladder neck.

PMID- 30194458
TI  - Pediatric radiology outreach - World Federation of Pediatric Imaging commentary
      on opportunities and challenges.

PMID- 30194459
TI  - Variability in billing practices for whole-body magnetic resonance imaging.

PMID- 30194460
TI  - Diagnostic efficacy of single-pass split-bolus multidetector computed tomography
      in pediatric oncology: a valid alternative to a standard monophasic protocol.

PMID- 30194461
TI  - Ultrasound with Doppler evaluation of congenital hepatic vascular shunts.
AB  - Congenital aberrant hepatic vascular communications result from intrahepatic or
      extrahepatic errors in vascular development or involution during the transition
      from fetal to newborn hepatic circulation. These hepatic vascular shunts can be
      fortuitously discovered and asymptomatic, or can cause symptoms of varying
      severity, often presenting diagnostic dilemmas. Some hepatic vascular shunts
      resolve spontaneously while others require interventional radiologic or surgical
      closure. Affected patients are often first studied with real-time and Doppler
      ultrasound, so radiologists should familiarize themselves with the expected
      ultrasound findings of these vascular shunts for effective diagnosis, triage and
      management. In this review, the authors focus on ultrasound and Doppler findings
      of hepatic vascular shunts with underlying embryology, clinical features and
      management strategies. Broadly, these aberrant hepatic vascular communications
      include portosystemic venous shunts (which can be intra- or extrahepatic and
      include persistent patent ductus venosus), arterioportal, arteriovenous or mixed
      shunts.

PMID- 30194462
TI  - The springtail Megaphorura arctica survives extremely high osmolality of body
      fluids during drought.
AB  - The springtail Megaphorura arctica Tullberg 1876 is widespread in the arctic and
      subarctic regions where it can be abundant along beaches. This species survives
      winters using cryoprotective dehydration as a cold tolerance strategy during
      which it becomes drastically dehydrated. Several studies have investigated the
      physiological responses associated with water loss of M. arctica under exposure
      to freezing temperatures, but little is known of the dynamics of body water and
      hemolymph osmolality when subjected to gradually increasing drought stress at
      temperatures above the freezing point. Therefore, an experiment was conducted in
      which M. arctica was subjected to relative humidities (RH) decreasing from fully
      saturated conditions to ca. 89%RH over a period of 30 days. During the experiment
      water content of springtails decreased from about 3 to ca. 0.5 mg mg-1 dry
      weight. Alongside with water loss, trehalose concentrations increased from nearly
      nothing to 0.12 mg mg-1 dry weight, which contributed to an increase in hemolymph
      osmolality from ca. 250 mOsm to at least 7 Osm. All springtails survived water
      loss down to 0.7 mg mg-1 dry weight and hemolymph osmolality of ca. 4 Osm, and
      about 60% of the springtails survived with only 0.5 mg water mg-1 dry weight and
      osmolality of ca. 7 Osm. At this level of dehydration, Differential Scanning
      Calorimetry analysis showed that most, but not all, osmotically active water was
      lost. It is discussed that the extensive dehydration must be associated with high
      concentrations of salts potentially causing denaturation and precipitation of
      cellular proteins. M. arctica is remarkably tolerant of dehydration, but because
      it does not endure loss of the osmotically inactive water it cannot be
      categorized as a truly anhydrobiotic species.

PMID- 30194464
TI  - Preliminary results from structural systems biology approach in Tetrahymena
      thermophila reveal novel perspectives for this toxicological model.
AB  - Tetrahymena is a unicellular microbial eukaryotic organism that has been used
      extensively in toxicology and environmental research. This work attempts to model
      for the first time the wiring of proteins involved in cellular mechanisms of Cd
      toxicity in Tetrahymena thermophila. 1975 high-confidence PPIs between 68 Cd
      binding proteins and 422 partners were inferred through a novel structural
      systems biology approach that utilizes comparative analysis between Tetrahymena
      and other eukaryotes for which experimentally supported protein interactomes
      exist. The PPIs of the potential network were confirmed by known domain
      interactions in the Protein Data Bank and its topological characteristics were
      compared with publicly available experimental information for T. thermophila. To
      experimentally validate the robustness of the proposed PPI network, the
      interaction between the two most interconnected hub proteins was detected through
      GST pull-down assay. Potential effects on Tetrahymena's cellular and metabolic
      processes by PPIs involving Cd-binding proteins were uncovered. Furthermore, 244
      PPIs in which Cd-binding proteins or/and their partners are encoded by orthologs
      of human disease genes in T. thermophila, but not in yeast, were identified and
      analyzed. The findings suggest that Tetrahymena could be possibly a useful model
      for an improved understanding of molecular mechanisms of Cd toxicity in human
      diseases.

PMID- 30194463
TI  - Individual variation of daily torpor and body mass change during winter in the
      large Japanese field mouse (Apodemus speciosus).
AB  - Daily torpor is a strategy used by some overwintering small endotherms to aid in
      energy conservation. However, the pattern of torpor varies among individuals
      within species and populations, even under the same environmental conditions,
      with significant implications for survival rate and reproductive success. Body
      mass is one factor that may influence this variation, especially in some small
      mammals that accumulate fat stores prior to overwintering. However, to our
      knowledge there has been no previous study examining the detailed relationships
      between torpor expression and body mass change in small mammals that hoard food
      as an energy resource during winter. The large Japanese field mouse, Apodemus
      speciosus, whose winter survival strategy depends on food caches instead of fat
      stores, displays daily torpor under artificial winter conditions (short-day
      photoperiod and cold). The present study clarifies the characteristics and
      patterns of daily torpor and body mass change in this species in the laboratory.
      Although expression of daily torpor was facilitated progressively as in other
      species, the observed patterns of torpor expression and body mass change showed
      considerable individual variation. Moreover, there was no obvious correlation
      between body mass and daily torpor expression. Therefore, it is suggested that in
      A. speciosus body mass may not contribute to individual variation of daily torpor
      during winter. Daily torpor during winter may be adjusted by not only mechanisms
      common to other small mammals, but also species-specific factors relating to the
      external or internal reserves of energy in small mammals.

PMID- 30194466
TI  - Impact of mild and moderate/severe vertebral fractures on physical activity: a
      prospective study of older women in the UK.
AB  - : Little is known about the long-term impact of vertebral fractures on physical
      activity. There is also uncertainty over the clinical significance of mild
      vertebral fracture. We showed that women with moderate/severe but not mild
      vertebral fracture do less walking duration and housework than those without
      fracture after 5.4 years of follow-up. INTRODUCTION: Little is known about the
      long-term impact of vertebral fractures on physical activities. There is also
      uncertainty over the clinical significance of mild fracture. Therefore, the aim
      of this study was to evaluate the prospective association between vertebral
      fracture and future physical activity. METHODS: This is a 5-year prospective
      study of a mixed community and secondary care cohort of women aged > 50 from the
      UK. Vertebral fractures were identified at baseline on radiographs or DXA-based
      Vertebral Fracture Assessment by a Quantitative Morphometric approach and defined
      as moderate/severe (>= 25% height decrease) or mild (20-24.9% height decrease).
      Physical activity data were collected 5.4 years later by self-completion
      questionnaires. Multivariable logistic regression was used to determine the
      association between presence of fracture and various physical activities while
      adjusting for potential confounders. RESULTS: Two hundred eighty-six women
      without, 58 with mild, and 69 with moderate/severe fracture were recruited. Those
      with mild and moderate/severe fracture were older than women without fracture and
      had more concomitant diseases at baseline. At 5.4 years follow-up, women with
      moderate/severe fracture self-reported shorter walking duration compared to those
      without fracture, even after adjusting for potential confounders (OR 2.96, 95%CI
      1.11-7.88, P = 0.030). No independent association was seen between the presence
      of mild fractures and reduced physical activity at follow-up. CONCLUSION: This is
      the first study of older women from the UK that explored the prospective
      association between vertebral fracture and physical activity duration.
      Moderate/severe fractures were associated with reduced walking duration. Mild
      fractures had no impact on future physical ability.

PMID- 30194465
TI  - Urinary creatinine excretion is related to short-term and long-term mortality in
      critically ill patients.
AB  - PURPOSE: Patients with reduced muscle mass have a worse outcome, but muscle mass
      is difficult to quantify in the ICU. Urinary creatinine excretion (UCE) reflects
      muscle mass, but has not been studied in critically ill patients. We evaluated
      the relation of baseline UCE with short-term and long-term mortality in patients
      admitted to our ICU. METHODS: Patients who stayed >= 24 h in the ICU with UCE
      measured within 3 days of admission were included. We excluded patients who
      developed acute kidney injury stage 3 during the first week of ICU stay. As
      muscle mass is considerably higher in men than women, we used sex-stratified UCE
      quintiles. We assessed the relation of UCE with both in-hospital mortality and
      long-term mortality. RESULTS: From 37,283 patients, 6151 patients with 11,198 UCE
      measurements were included. Mean UCE was 54% higher in males compared to females.
      In-hospital mortality was 17%, while at 5-year follow-up, 1299 (25%) patients had
      died. After adjustment for age, sex, estimated glomerular filtration rate, body
      mass index, reason for admission and disease severity, patients in the lowest UCE
      quintile had an increased in-hospital mortality compared to the patients in the
      highest UCE quintile (OR 2.56, 95% CI 1.96-3.34). For long-term mortality, the
      highest risk was also observed for patients in the lowest UCE quintile (HR 2.32,
      95% CI 1.89-2.85), independent of confounders. CONCLUSIONS: In ICU patients
      without severe renal dysfunction, low urinary creatinine excretion is associated
      with short-term and long-term mortality, independent of age, sex, renal function
      and disease characteristics, underscoring the role of muscle mass as risk factor
      for mortality and UCE as relevant biomarker.

PMID- 30194468
TI  - Knee pain is associated with lower back pain in young baseball players: a cross
      sectional study.
AB  - PURPOSE: Considerable research has focused on shoulder and elbow injuries among
      baseball players; however, although lumbar spine and knee injuries are commonly
      experienced, they are less frequently studied. During common motions in baseball,
      such as throwing, hitting, and running, energy is transferred from the lower
      extremities through the lower back to the upper body. Lower extremity pain, as
      well as lower back pain (LBP), can disrupt the kinematic chain, and it is
      important to understand the association between lower extremity complaints and
      LBP. The purpose of this study was to elucidate the association between knee pain
      and LBP among young baseball players. METHODS: A cross-sectional study was
      conducted with young baseball players (aged 6-15 years, n = 1,609) using a self
      reported questionnaire. Multivariate logistic regression models were used for
      analyses. Variables considered in the models were sex, age, body mass index, team
      levels, number of days of training per week, number of hours in practice per day
      on weekdays and weekend, frequency of participation in games, practice intensity,
      and player position. RESULTS: The point prevalence of LBP and knee pain was 8.4%
      and 13.1%, respectively. Knee pain was significantly associated with LBP. Using
      the absence of knee pain as a reference, the adjusted odds ratio (95% confidence
      interval) for LBP was 5.83 (3.93-8.65) (p < 0.001) in the presence of knee pain.
      CONCLUSIONS: Knee pain was associated with LBP among young baseball players.
      Clinicians should pay attention to knee complaints to prevent and treat LBP among
      young baseball players. LEVEL OF EVIDENCE: III.

PMID- 30194467
TI  - Notch in skeletal physiology and disease.
AB  - Notch (Notch1 through 4) are transmembrane receptors that play a fundamental role
      in cell differentiation and function. Notch receptors are activated following
      interactions with their ligands in neighboring cells. There are five classic
      ligands termed Jagged (Jag)1 and Jag2 and Delta-like (Dll)1, Dll3, and Dll4.
      Recent work has established Notch as a signaling pathway that plays a critical
      role in the differentiation and function of cells of the osteoblast and
      osteoclast lineages and in skeletal development and bone remodeling. The effects
      of Notch are cell-context dependent, and the four Notch receptors carry out
      specific functions in the skeleton. Gain- and loss-of-function mutations of
      components of the Notch signaling pathway result in a variety of congenital
      disorders with significant craniofacial and skeletal manifestations. The Notch
      ligand Jag1 is a determinant of bone mineral density, and Notch plays a role in
      the early phases of fracture healing. Alterations in Notch signaling are
      associated with osteosarcoma and with the metastatic potential of carcinoma of
      the breast and of the prostate. Controlling Notch signaling could prove useful in
      diseases of Notch gain-of-function and in selected skeletal disorders. However,
      clinical data on agents that modify Notch signaling are not available. In
      conclusion, Notch signaling is a novel pathway that regulates skeletal
      homeostasis in health and disease.

PMID- 30194469
TI  - Younger patients and smokers report a higher level of pain after knee
      arthroscopy: a clinical and experimental study including synovial metabolism.
AB  - PURPOSE: Factors associated with post-surgical pain are not fully explored. The
      aim of this study was to identify determinants of postoperative pain after
      arthroscopic surgery of the knee. Synovial tissue metabolism was analysed by
      microdialysis and the association with individual and peri-surgical factors to
      identify determinants important for pain management and thus patient
      satisfaction. METHODS: Cross-sectional study of 57 patients (22 women) with
      median age of 39 years. All patients were operated on with arthroscopic surgery
      of the knee and monitored postoperatively with synovial microdialysis. The cross
      sectional cohort was investigated to determine local tissue levels of
      inflammatory and metabolic compounds along with postoperative pain experience.
      MEASUREMENTS: pain was determined by visual analogue scale (VAS). Postoperative
      synovial tissue levels of prostaglandin E2 (PGE2), glucose, and glycerol were
      measured by microdialysis in the knee synovium. Patients reporting VAS >= 4
      received rescue pain medication with systemic opioids. RESULTS: Initial results
      indicated that patients with pain (interpreted as having VAS >= 4), i.e. those
      receiving rescue medication with systemic opioids, were of a younger age (p =
      0.04), lower body weight (p = 0.02), had a lower BMI (p = 0.04) and/or were
      smokers (p = 0.02). A closer analysis using multinomial logistic regression
      showed a significantly higher amount of pain in smokers (p = 0.01) and patients
      of a younger age (p = 0.02). A significant correlation was also found between VAS
      and duration of surgery (p = 0.007). No significant correlation could be found
      between VAS and synovial levels of PGE2, glycerol and glucose, but a
      statistically significant decline with time of PGE2 in both groups. CONCLUSIONS:
      The results from this study show a significantly higher frequency of pain, post
      surgery among younger patients (p = 0.02) and smokers (p = 0.01), as well as an
      association between pain and length of surgery (p = 0.007). These findings point
      out individual factors useful for the prediction of postoperative pain after
      arthroscopic surgery and are clinically important for personalized pain
      management. LEVEL OF EVIDENCE: II.

PMID- 30194470
TI  - [Human papillomavirus disease burden in men : HPV prevention is a man's
      business].
AB  - Due to the lack of an established school-based immunization program, the initial
      German public funded girls-only human papillomavirus (HPV)-vaccination strategy
      failed. Over the last decade, the female coverage rates have not exceeded much
      more than 40%, thus, missing herd immunity for boys. Therefore, the German HPV
      immunization program has been revised and currently recommends a gender-neutral
      HPV vaccination for all children aged 9-14 years to prevent all HPV-related
      tumors which can be prevented by immunization. In order to correct the mistaken
      German impression of this being an  issue relevant only to females, this article
      highlights the HPV disease burden in men which mostly can be prevented by timely
      immunization of boys. German urologists have started a campaign: HPV prevention
      is a man's business.

PMID- 30194472
TI  - Inter-observer variability of manual contour delineation of structures in CT.
AB  - PURPOSE: To quantify the inter-observer variability of manual delineation of
      lesions and organ contours in CT to establish a reference standard for volumetric
      measurements for clinical decision making and for the evaluation of automatic
      segmentation algorithms. MATERIALS AND METHODS: Eleven radiologists manually
      delineated 3193 contours of liver tumours (896), lung tumours (1085), kidney
      contours (434) and brain hematomas (497) on 490 slices of clinical CT scans. A
      comparative analysis of the delineations was then performed to quantify the inter
      observer delineation variability with standard volume metrics and with new group
      wise metrics for delineations produced by groups of observers. RESULTS: The mean
      volume overlap variability values and ranges (in %) between the delineations of
      two observers were: liver tumours 17.8 [-5.8,+7.2]%, lung tumours 20.8 [
      8.8,+10.2]%, kidney contours 8.8 [-0.8,+1.2]% and brain hematomas 18 [-6.0,+6.0]
      %. For any two randomly selected observers, the mean delineation volume overlap
      variability was 5-57%. The mean variability captured by groups of two, three and
      five observers was 37%, 53% and 72%; eight observers accounted for 75-94% of the
      total variability. For all cases, 38.5% of the delineation non-agreement was due
      to parts of the delineation of a single observer disagreeing with the others. No
      statistical difference was found for the delineation variability between the
      observers based on their expertise. CONCLUSION: The variability in manual
      delineations for different structures and observers is large and spans a wide
      range across a variety of structures and pathologies. Two and even three
      observers may not be sufficient to establish the full range of inter-observer
      variability. KEY POINTS: * This study quantifies the inter-observer variability
      of manual delineation of lesions and organ contours in CT. * The variability of
      manual delineations between two observers can be significant. Two and even three
      observers capture only a fraction of the full range of inter-observer variability
      observed in common practice. * Inter-observer manual delineation variability is
      necessary to establish a reference standard for radiologist training and
      evaluation and for the evaluation of automatic segmentation algorithms.

PMID- 30194471
TI  - [Unilateral combined strabismus surgery to correct esotropia : Video article on
      recession of the medial rectus muscle and plication of the lateral rectus
      muscle].
AB  - OBJECTIVE OF SURGERY: The aim of strabismus surgery to correct esotropia is
      orthotropic alignment or microstrabismus to achieve best possible binocularity, a
      larger visual field, better appearance, and a frequently connected improved self
      esteem. A widely used technique to correct esotropia is combined unilateral
      strabismus surgery with recession of the medial rectus muscle and plication of
      the lateral rectus muscle. INDICATIONS: Indications are esotropia of various
      origins or decompensating esophoria over 15 prism diopters. CONTRAINDICATIONS:
      Absolute contraindications are insufficient optical correction of hyperopia and
      sixth nerve palsy with unfinished spontaneous regeneration. A relative
      contraindication in children is untreated amblyopia. SURGICAL TECHNIQUE: The
      technique consists of unilateral recession of the medial rectus muscle and
      tucking of the lateral rectus muscle. The surgical technique is demonstrated in
      detail in two videos of the operation, which are available online. FOLLOW-UP:
      Antibiotic and lubricating eye drops are applied during the first week after
      surgery. In the early postoperative period, patients should be monitored for
      postoperative infection, conjunctival dehiscence, or corneal laceration. We
      review patients 4 months postoperatively for evaluation of the long-term result.
      EVIDENCE: Recent randomized controlled studies have shown that unilateral medial
      rectus muscle recession and resection surgery is comparable to bilateral
      recession surgery with regards to postoperative results in esotropia. The effect
      of lateral rectus muscle tuck is comparable to muscle resection with less trauma
      and potential reversibility during the first days after surgery.

PMID- 30194473
TI  - Comparison of radiographs, tomosynthesis and CT with metal artifact reduction for
      the detection of hip prosthetic loosening.
AB  - OBJECTIVES: To evaluate the diagnostic performance of digital tomosynthesis (DTS)
      for the diagnosis of hip prosthesis loosening (PL) compared with conventional
      radiographs and CT with metal artifact reduction (CT-MAR). METHODS: Forty-nine
      patients with painful hip prosthesis were prospectively included and underwent
      anteroposterior and lateral radiographs, anteroposterior DTS and CT-MAR of the
      hip. This study was approved by the local ethics committee, and all patients
      signed an informed consent form. Images were evaluated independently by two
      radiologists. Periprosthetic radiolucent lines wider than 2 mm found in two or
      more Gruen or De Lee and Charnley zones were considered diagnostic of PL. All
      cases of PL were confirmed surgically. Patients with a stable radiological follow
      up for at least 1 year with an alternative cause for the symptoms or with no
      surgical evidence of PL were considered PL negative. RESULTS: There were 21 cases
      of PL, 9 unilateral and 12 bilateral. For both the acetabular and femoral sides,
      DTS had a specificity for PL detection similar to that of conventional
      radiographs and CT-MAR (98.5-100%, 96.9%-100% and 96.9-95.4% respectively for
      both readers) and a sensitivity similar to conventional radiographs (39.9-45.4%
      versus 33.3-51.5% for both readers) but lower than CT-MAR (84.85% for both
      readers). The interobserver agreement was 0.84 for CT-MAR, 0.53 for DTS and 0.39
      for conventional radiographs. CONCLUSION: DTS has a similar diagnostic
      performance to radiographs for the diagnosis of PL with a better interobserver
      agreement. The sensitivity however remains lower than that of CT-MAR. KEY POINTS:
      * Plain radiograph is still the first imaging step when hip prosthesis loosening
      is suspected. * Interobserver agreement is better with digital tomosynthesis than
      radiographs. * Sensitivity of CT with state-of-the-art metal artifact reduction
      is superior to that of digital tomosynthesis.

PMID- 30194474
TI  - [Structures in cardiology].

PMID- 30194475
TI  - Long-term symptom improvement and patient satisfaction after AV-node ablation vs.
      pulmonary vein isolation for symptomatic atrial fibrillation: results from the
      German Ablation Registry.
AB  - BACKGROUND: We aimed to compare patient characteristics and outcome of patients
      who had either undergone pulmonary vein isolation (PVI) or AV-node ablation (AVN)
      to control AF-related symptoms. METHODS: From the German Ablation Registry, we
      analyzed data of 4444 patients (95%) who had undergone PVI and 234 patients (5%)
      with AVN. RESULTS: AVN patients were on average 10 years older than PVI patients
      (71 +/- 10 vs. 61 +/- 10 years, p < 0.001) with 33% aged > 75 years. AVN patients
      had significantly more cardiovascular comorbidities (diabetes 21% vs. 8%, renal
      insufficiency 24% vs. 3%, underlying heart disease 80% vs. 36%, severely reduced
      left ventricular function 28% vs. 1%, all p < 0.001). Significantly more PVI
      patients had paroxysmal AF (63% vs. 18%, p < 0.001), and more AVN patients had
      long-standing persistent AF (44% vs. 7%, p < 0.001). At 1-year follow-up,
      mortality in the AVN group was much higher (Kaplan-Meier estimates 9.8% vs.
      0.5%). 20% of PVI patients had undergone another ablation vs. 3% AVN patients (p
      < 0.001). Symptomatic improvement was equally achieved in about 80%. Re
      hospitalization for cardiovascular reasons occurred significantly more often in
      PVI vs. AVN patients (31% vs. 18%, p < 0.001). CONCLUSION: In the large German
      Ablation Registry, AVN ablation was performed much less frequently than PVI for
      symptomatic treatment of AF and typically in older patients with more
      comorbidity. Symptomatic improvement was similar in both groups. Hospitalizations
      for cardiovascular reasons were lower in AVN patients despite older age and more
      cardiovascular comorbidities. 20% of PVI patients had undergone at least one re
      ablation.

PMID- 30194476
TI  - A Mild Inhibition of Cathepsin K Paradoxically Stimulates the Resorptive Activity
      of Osteoclasts in Culture.
AB  - Cathepsin K (CatK) inhibition allows reducing bone resorption with specific
      advantages compared to the existing anti-osteoporosis drugs. Its clinical use
      appears even more promising with the recent development of ectosteric inhibitors.
      A confusing observation, however, is that a low dose of the active site CatK
      inhibitor odanacatib (ODN) was reported to decrease bone mineral density and
      increase serum levels of the bone resorption marker carboxy-terminal collagen
      crosslinks (CTX). The present study provides a possible explanation for this
      paradox. The resorptive activity of human osteoclasts seeded on bone slices was
      inhibited when subjected to ODN at doses of 20 nM, but about 100-fold lower doses
      induced a significant increase in CTX levels and in eroded surface (12 repeats).
      This low-dose-induced stimulation was prevented by inhibition of non-CatK
      cysteine proteinases, thereby indicating that the stimulation results from an
      interplay between CatK and other cysteine proteinases. Effective interplay
      between these proteinases was also shown in enzymatic assays where the CatK
      mediated degradation of collagen was enhanced upon addition of cathepsins B or L.
      Furthermore, extracts of osteoclasts subjected to a low dose of ODN showed higher
      levels of cathepsin B compared with extracts of control osteoclasts. In
      conclusion, the low-dose-induced stimulation of resorption observed in the
      clinical study can be reproduced in osteoclasts cultured in the absence of any
      other cell. Our data support an osteoclast-intrinsic mechanism where a mild
      inhibition of CatK results in increased levels of other proteinases contributing
      to the collagen degradation process.

PMID- 30194477
TI  - Can time to healing in pediatric blunt splenic injury be predicted?
AB  - BACKGROUND: Current consensus guidelines do not recommend routine follow-up
      imaging for blunt splenic injury (BSI) in children. However, repeat imaging is
      recommended based on persistent symptoms. Wide variation of practice continues to
      exist among surgeons. By defining the natural evolution of BSI, we sought to
      identify patients at higher risk for delayed healing who could benefit from
      outpatient imaging. METHODS: A retrospective review of all children with BSI at a
      Level 1 Pediatric Trauma Center was completed. Grade of injury, hospital course,
      laboratory values and follow-up imaging results were obtained. Injured spleens
      were classified as 'healed', 'healing' (with echogenic scar), or 'non-healing'
      with persistence of parenchymal abnormalities. RESULTS: Between 2000 and 2014,
      222 patients with BSI were identified. Seven patients (3%) underwent immediate
      splenectomy. Packed red blood cell transfusion was required in 13 (6%) of the 222
      patients, and 3 (2%) of 145 with isolated splenic injuries. Seventy-one percent
      of patients underwent additional imaging 2-74 weeks post-injury. A receiver
      operating characteristics (ROC) curve was used to establish the relationship
      between sensitivity and specificity of capturing non-healing spleens over time.
      Optimal timing for post-injury imaging for grades I-II was 7-8 weeks; healing of
      higher-grade injuries could not accurately be predicted. CONCLUSIONS: If return
      to full physical activity, in particular contact sports, is contingent upon
      documented healing of the splenic parenchyma after blunt trauma in the pediatric
      population, follow-up imaging for low-grade injuries is best obtained around 7-8
      weeks. No such recommendations can be made for high-grade splenic injuries, as
      the exact time to healing cannot be predicted based on initial data. LEVEL OF
      EVIDENCE: IV. Diagnostic test.

PMID- 30194478
TI  - ?

PMID- 30194480
TI  - Follicular competition in cows: the selection of dominant follicles as a
      synergistic effect.
AB  - The reproductive cycle of mono-ovulatory species such as cows or humans is known
      to show two or more waves of follicular growth and decline between two successive
      ovulations. Within each wave, there is one dominant follicle escorted by
      subordinate follicles of varying number. Under the surge of the luteinizing
      hormone a growing dominant follicle ovulates. Rarely the number of ovulating
      follicles exceeds one. In the biological literature, the change of hormonal
      concentrations and individually varying numbers of follicular receptors are made
      responsible for the selection of exactly one dominant follicle, yet a clear cause
      has not been identified. In this paper, we suggest a synergistic explanation
      based on competition, formulated by a parsimoniously defined system of ordinary
      differential equations (ODEs) that quantifies the time evolution of multiple
      follicles and their competitive interaction during one wave. Not discriminating
      between follicles, growth and decline are given by fixed rates. Competition is
      introduced via a growth-suppressing term, equally supported by all follicles. We
      prove that the number of dominant follicles is determined exclusively by the
      ratio of follicular growth and competition. This number turns out to be
      independent of the number of subordinate follicles. The asymptotic behavior of
      the corresponding dynamical system is investigated rigorously, where we
      demonstrate that the [Formula: see text]-limit set only contains fixed points.
      When also including follicular decline, our ODEs perfectly resemble ultrasound
      data of bovine follicles. Implications for the involved but not explicitly
      modeled hormones are discussed.

PMID- 30194479
TI  - Application of Bacillus velezensis NJAU-Z9 Enhanced Plant Growth Associated with
      Efficient Rhizospheric Colonization Monitored by qPCR with Primers Designed from
      the Whole Genome Sequence.
AB  - Plant growth-promoting rhizobacteria (PGPR) have been reported to influence plant
      growth, yield, and nutrient uptake by an array of mechanisms. Uncovering the
      behavioral dynamics of PGPR is one of the most important issues necessary for
      understanding their functional performances. In this study, strain NJAU-Z9 which
      was found to possess complex functions and efficient rhizospheric colonization
      ability was selected from plenty of bacterial strains isolated randomly from the
      pepper rhizosphere soil and identified as Bacillus velezensis. Repeated seedling
      nursing tests performed absolute growth-promoting advantage for the novel
      isolated strain. After that, primers for the quantitative detection were designed
      based on its whole genome sequence (WGS), and a real-time PCR method was utilized
      to explore strategies for monitoring the strain in natural soil and in the pepper
      rhizosphere. Results showed based on the whole genome, two primers were
      identified as NJAU-Z9-specific quantitative PCR primers. Two seasonal pot
      experiments demonstrated that strain NJAU-Z9 effectively colonized the
      rhizosphere measured by the novel abundance detecting strategy, improved plant
      growth, and showed a positive correlation between bacterial number and biomass.
      This study offers a strategy based on a real-time PCR method for directly
      monitoring B. velezensis strain NJAU-Z9 in the soil and the rhizosphere and
      provides a reference for the quantitative study of other PGPR strains based on
      WGSs.

PMID- 30194481
TI  - [InterAtrial Shunt Device in diastolic heart failure].
AB  - All types of heart failure are associated with reduced cardiac output and/or
      increased left atrial (LA) pressure. In diastolic heart failure (heart failure
      with preserved ejection fraction [HFpEF]), the increased LA pressure plays a
      central role, leading to pulmonary venous hypertension (PVH) and increased
      pulmonary artery pressure. These pressure parameters are presumably decisive for
      the symptoms and mortally of heart failure, particularly of the diastolic form.
      This is the basis for treatment with an interarterial shunt to reduce LA pressure
      in patients with diastolic heart failure and PVH. At first glance, this appears
      paradoxical, since closure of an atrial septum defect serves to prevent increased
      pulmonary vascular resistance and paradoxical embolism. Prevention of increased
      pulmonary vascular resistance and paradoxical embolism is thus an essential
      aspect in the development of devices for establishing an interarterial shunt.
      Reports on the InterAtrial Shunt Device (IASD(r)) and the V-Wave have been
      published, both of which can be implanted with a low risk and few complications.
      The V-Wave device is equipped with a valve to prevent paradoxical embolisms.
      However, paradoxical embolisms were also not observed with the IASD(r), and the
      valve of the V-Wave exhibited considerable degenerative changes and valve
      closure. Hemodynamic and clinical data of patients with an IASD(r) or an open V
      Wave device demonstrated a sustained hemodynamic improvement. Physical
      performance capacity and quality of life were increased. Whether IASD(r) may be
      broadly applicable in patients with diastolic heart failure is currently under
      investigation. In selected highly symptomatic patients with diastolic heart
      failure and PVH, the IASD(r) is already in clinal use.

PMID- 30194482
TI  - [Angina pectoris in a 47-year-old athletic man with psoriasis vulgaris].
AB  - A 47-year-old man presented with angina pectoris complaints in the chest pain
      unit. Due to psoriasis and psoriatic arthritis he had been systemically treated
      for 4 years. Because of an increased cardiovascular risk profile, coronary heart
      disease (CHD) was suspected and an invasive coronary diagnosis was performed. In
      the cardiac catheterization, CHD could be detected and treated in the same
      session. The risk of CHD in patients with psoriasis is increased due to a higher
      incidence of risk factors but also the disease itself. Patients with psoriasis
      should regularly undergo cardiovascular risk screening.

PMID- 30194484
TI  - Correction to: Bartonella and Rickettsia Infections in Haematophagous Spinturnix
      myoti Mites (Acari: Mesostigmata) and their Bat Host, Myotis myotis
      (Yangochiroptera: Vespertilionidae), from Poland.
AB  - The original version of this article published online (27 August 2018)
      unfortunately contained a mistake regarding an affiliation of Dr. Edyta
      Podsiadly, one of the authors.

PMID- 30194483
TI  - High-Throughput Sequencing Analysis of the Bacterial Community in Stone Fruit
      Phloem Tissues Infected by "Candidatus Phytoplasma prunorum".
AB  - "Candidatus Phytoplasma prunorum" (CPp) is a highly destructive phytopathogenic
      agent in many stone fruit-growing regions in Europe and the surrounding
      countries. In this work, we focused on documenting entire bacterial community in
      the phloem tissues of 60 stone fruit trees. Nested PCR and two real-time PCR
      assays were used to select CPp-positive (group A) and CPp-negative samples (group
      B). Afterwards, high-throughput amplicon sequencing was performed to assess
      bacterial community compositions in phloem tissues. The bacterial composition in
      phloem tissue consisted of 118 distinct genera, represented mainly by
      Pseudomonas, Acinetobacter, Methylobacterium, Sphingomonas, and Rhizobium.
      Statistics showed that CPp influenced the bacterial composition of infected
      plants (group A) and that the bacterial community depended on the geographical
      origin of the sample. This is the first work focusing on an analysis of the
      influence of CPp on the bacteria coexisting in the phloem tissues of stone fruit
      trees.

PMID- 30194485
TI  - POLE gene hotspot mutations in advanced pancreatic cancer.
AB  - PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease,
      lacking relevant prognostic and predictive biomarkers. DNA polymerase epsilon
      (POLE) has important functions in the maintenance of genetic stability during DNA
      replication and has previously been associated with favorable prognosis in
      endometrial and colorectal cancer. However, its relevance in advanced pancreatic
      cancer (aPDAC) has not been examined to date. METHODS: Using pyrosequencing on
      tumoral DNA extracted from 60 samples from the AIO-PK0104 study as well as 55
      samples from completed translational trials, we examined POLE hotspot mutations
      in exon 9 (P286R) and exon 13 (V411R/L/M) in the POLE gene exonuclease domain.
      DNA extracted from 37 endometrial carcinomas were tested as positive controls.
      Publically available sequencing databases were searched for POLE mutations in
      PDAC samples. RESULTS: Fifty-three patients (pts) were men, 62 pts were women,
      median age was 61.2 years. Median overall survival (OS) was 7.4 months and median
      progression free survival (PFS) was 4.0 months. In four of the 37 endometrial
      carcinomas POLE mutations were detected in exon 9 (10.8%) and none in exon 13. In
      none of the overall 115 aPDAC tumors POLE gene hotspot mutations could be
      detected. CONCLUSION: Mutations in the hotspot regions of exon 9 and 13 of the
      POLE gene are very rare events in advanced pancreatic cancer. Thus, it is
      unlikely that POLE gene mutations contribute to genetic instability in the vast
      majority of aPDAC. POLE mutation does not serve as a relevant biomarker and
      should not be tested on a regular basis in PDAC.

PMID- 30194486
TI  - Recognising and reacting to angry and happy facial expressions: a diffusion model
      analysis.
AB  - Researchers have reported two biases in how people recognise and respond to angry
      and happy facial expressions: (1) a gender-expression bias (Becker et al. in J
      Pers Soc Psychol, 92(2):179-190, https://doi.org/10.1037/0022-3514.92.2.179 ,
      2007)-faster identification of male faces as angry and female faces as happy and
      (2) an approach-avoidance bias-faster avoidance of people who appear angry and
      faster approach responses people who appear happy (Heuer et al. in Behav Res The,
      45(12):2990-3001, https://doi.org/10.1016/j.brat.2007.08.010 2007; Marsh et al.
      in Emotion, 5(1), 119-124, https://doi.org/10.1037/1528-3542.5.1.119 , 2005;
      Rotteveel and Phaf in Emotion 4(2):156-172, https://doi.org/10.1037/1528
      3542.4.2.156 , 2004). The aim of the current research is to gain insight into the
      nature of such biases by applying the drift diffusion model to the results of an
      approach-avoidance task. Sixty-five participants (33 female) identified faces as
      either happy or angry by pushing and pulling a joystick. In agreement with the
      original study of this effect (Solarz 1960) there were clear participant gender
      differences-both the approach avoidance and gender-expression biases were larger
      in magnitude for female compared to male participants. The diffusion model
      results extend recent research (Krypotos et al. in Cogn Emot 29(8):1424-1444,
      https://doi.org/10.1080/02699931.2014.985635 , 2015) by indicating that the
      gender-expression and approach-avoidance biases are mediated by separate
      cognitive processes.

PMID- 30194487
TI  - [Proximal humeral fractures-Where do we stand today? : Comments on the "Proximal
      fracture of the humerus evaluation by randomization (PROFHER)" study].
AB  - The PROFHER study is a multicenter randomized controlled trial of 250 out of 1250
      patients assessed for eligibility with dislocated proximal humeral fractures with
      involvement of the surgical neck. These patients were randomized either for
      surgery or conservative treatment. Patients with comorbidities that precluded
      surgery, lack of mental capacity, luxation fractures or clear indications for
      surgery from the authors' perspective were excluded. To evaluate the outcome,
      standardized self-assessment methods were used (patient reported outcome [PRO]),
      including the Oxford shoulder score (OSS). The results showed no differences in
      the primary and secondary self-assessment outcome scores after both 2 and 5
      years. Although no significant differences could be detected between both groups,
      no clear statement could be deduced from the PROFHER study with respect to which
      patients would benefit from an operative treatment. Nevertheless, the PROFHER
      study provides a valuable and important addition to the literature on this
      heavily debated topic. The purpose of this review is to critically evaluate the
      PROFHER study within the existing literature regarding inclusion of patients,
      fracture treatment and evaluation of the results.

PMID- 30194488
TI  - Optical properties of anatase TiO2: synergy between transition metal doping and
      oxygen vacancies.
AB  - Charge carriers (electrons and holes) are generated on the TiO2 using UV
      radiation; this excitation energy can be reduced by modifying the material
      electronic structure, for example, by doping or creating oxygen vacancies. Here,
      the electronic structure of a transition metal-doped anatase, bulk and surface,
      and their interaction with oxygen vacancies are studied using density functional
      theory. The visible light response of metal-doped TiO2 (101) is also determined.
      Transition metals generate intra-band gap states, which reduce the excitation
      energy but may also act as charge recombination sites. Dopants Fe, Co, and Ni
      remarkably enhance the visible light response due to the states in the middle of
      the gap. However, Co and Ni create heavier charge carriers. Our results show that
      Pd and Pt-doped TiO2 generate states near the valence and conduction band with a
      "clean" band gap (without states in the middle of the gap). Moreover, Pt-doped
      TiO2 maintains the charge mobility because it presents a small charge carriers
      mass. Hence, Pt-doped TiO2 represents the best alternative to activate TiO2 under
      visible light. The optical response of transition metal-doped TiO2 follows the
      order 3d > 4d > 5d. The oxygen vacancies reduce the response of metal-doped TiO2
      to visible light because the unpaired electrons generated occupy the empty states
      of metal-doping. Graphical Abstract Density of states of TiO2 (101) surface doped
      with transition metals and oxygen vacancies.

PMID- 30194489
TI  - Primary classic Hodgkin lymphoma of the ileum and Epstein-Barr virus
      mucocutaneous ulcer of the colon: two entities compared.
AB  - Primary classic Hodgkin lymphoma of the gastrointestinal tract represents a rare
      occurrence. A full patient's work-up is essential in order to exclude a secondary
      intestinal involvement. Histologically Epstein-Barr virus mucocutaneous ulcer
      closely resembles Hodgkin lymphoma. The differential diagnosis between these two
      entities is relevant, since both the therapeutic approach and the clinical
      behavior are different. Herein, we describe a case of primary classic Hodgkin
      lymphoma arising in the ileum and a case of Epstein-Barr virus mucocutaneous
      ulcer of the colon, focusing on the main clinicopathological differences.

PMID- 30194490
TI  - [The knee joint in rheumatoid arthritis-current orthopaedic surgical treatment
      options].
AB  - The knee joint is often involved in rheumatoid arthritis. Despite ever-improving
      medical antirheumatic therapies, surgical treatment continues to play an
      important role in optimal multidisciplinary care. The aim of the present work is
      to process current orthopedic surgical therapy procedures on the knee joint
      according to disease stage. In the early phase, joint-preserving arthroscopic
      procedures for synovectomy are used. In advanced joint destruction, joint
      function can be restored by total knee arthroplasty. Of central importance for
      optimal patient care are individual treatment and good interdisciplinary
      coordination of all involved specialist groups.

PMID- 30194491
TI  - In focus in HCB.

PMID- 30194492
TI  - Does a homeopathic medicine reduce hot flushes induced by adjuvant endocrine
      therapy in localized breast cancer patients? A multicenter randomized placebo
      controlled phase III trial.
AB  - PURPOSE: Endocrine therapy (ET) used to reduce the risk of recurrence in hormone
      receptor-expressing disease (75% of breast cancers) is associated with worsening
      of climacteric symptoms with a negative impact on quality of life (QoL).
      Homeopathy might allow a better management of hot flushes (HF). METHODS: In this
      multicenter randomized double-blind placebo-controlled phase III study (
      ClinicalTrials.gov NCT01246427), we enrolled >= 18 years old women with
      histologically proven non metastatic localized breast cancer, with Eastern
      Cooperative Oncology Group-Performance Status (ECOG-PS) <= 1, treated for at
      least 1 month with adjuvant ET, and complaining about moderate to severe HF.
      Patients should not be scheduled for chemotherapy or radiotherapy, and had no
      associated pathology known to induce HF. After a 2- to 4-week placebo
      administration, we randomly assigned (1:1) patients with HFS >= 10 using an
      interactive web-based centralized platform to BRN-01 homeopathic medicine complex
      (Actheane(r)) in arm A or Placebo (Arm P). Randomization was stratified by
      adjuvant ET (taxoxifen/aromatase inhibitor) and recruiting site. HF scores (HFS)
      were calculated as the mean of HF frequencies before randomization, at 4, and at
      8 weeks post-randomization (pre-, 4w,- and 8w-) weighted by a 4-level intensity
      scale. Primary endpoint was assessed at 4-week post-randomization, as the
      variation between pre- and 4w-HFS. Secondary endpoints included HFS variation
      between pre- and 8w-HFS, compliance and tolerance assessed 8 weeks after
      randomization, and QoL and satisfaction assessed at 4- and 8-week post
      randomization. RESULTS: Two hundred ninety-nine patients were included, and 138
      (46.2%) randomized (A, 65; P, 73). Median 4w-HFS absolute variation (A, - 2.9; P,
      - 2.5 points, p = 0.756) and relative decrease (A, - 17%; P, - 15%, p = 0.629)
      were not statistically different. However, 4w-HFS decreased for 46 (75%) in A vs
      48 (68%) patients in P arm. 4w-QoL was stable or improved for respectively 43
      (72%) vs 51 (74%) patients (p = 0.470). CONCLUSIONS: The efficacy endpoint was
      not reached, and BRN-01 administration was not demonstrated as an efficient
      treatment to alleviate HF symptoms due to adjuvant ET in breast cancer patients.
      However, the study drug administration led to decreased HFS with a positive
      impact on QoL. Without any recommended treatment to treat or alleviate the HF
      related disabling symptoms, Actheane(r) could be a promising option, providing an
      interesting support for better adherence to ET, thereby reducing the risk of
      recurrence with a good tolerance profile.

PMID- 30194493
TI  - Kinetic modeling, recovery, and molecular characterization of poly-beta
      hydroxybutyrate polymer in Acinetobacter baumannii isolate P39.
AB  - To control the poly-beta-hydroxybutyrate (PHB) biopolymer production by
      Acinetobacter baumannii isolate P39 kinetic modeling of the fermentation process,
      polymer downstream processing, enzymological analysis, and molecular
      characterization of PHA synthase, key biosynthetic enzyme, should be addressed.
      A. baumannii isolate P39 produced 0.15 g/L PHB after 24 h of incubation with a
      polymer content of 28% per dry weight. Logistic and Leudeking-Piret models were
      used for describing cell growth and PHB production, respectively. They showed
      good agreement with the experimental data describing both cell growth and PHB
      production (average regression coefficient r2:0.999). The growth-associated
      production of PHB biopolymer as an electron acceptor was confirmed using
      Leudeking-Piret model and victim substrate experiment. The best method of
      recovery of PHB biopolymer was chemical digestion using sodium hypochlorite,
      since it produced the largest amount of polymer and highest molecular weight
      (16,000 g/mole) in comparison to other recovery methods. DTNB assay showed high
      activity of PHA synthase enzyme, 600 U activity, and 153.8 U/mg specific
      activity. Molecular analysis of PHA synthase enzyme confirmed class III identity.
      Taken together, micelle model was proposed for polyhydroxybutyrate formation in
      A. baumannii isolate P39.

PMID- 30194494
TI  - Electrochemical immunoassay for lactalbumin based on the use of ferrocene
      modified gold nanoparticles and lysozyme-modified magnetic beads.
AB  - The authors describe a method for electrochemical determination of the breast
      cancer biomarker alpha-lactalbumin (alpha-LA) using disposable screen-printed
      carbon electrodes (SPCEs). Lysozyme-conjugated Fe3O4 nanoparticles (Lys-Fe3O4NPs)
      were used to capture alpha-LA on the surface of the SPCEs which then is trapped
      in an immunosandwich using secondary antibodies labeled with ferrocene-modified
      gold nanoparticles. The amperometric response of ferrocene (recorded at +0.1 V
      vs. silver pseudo-reference electrode) as well as the electrocatalytic activity
      of gold nanoparticles on the hydrogen evolution reaction (recorded at -1.0 V Vs
      Ag pseudo-reference electrode) was exploited to sense alpha-LA. A sensitive
      voltammetric response is observed, with (a) a sensitivity of 0.8789 MUA.nM-1.cm
      2, (b) a detection limit (LOD, at S/N = 3) as low as 0.07 ng.mL-1, and (c) linear
      response in the 0.75 to 630 ng mL-1 alpha-LA concentration range. The assay is
      selective and reproducible, and the SPCEs have good storage stability. The SPCEs
      were applied (a) to the analysis of (spiked) maternal milk, (b) of spiked serum
      from healthy and pregnant persons, and (c) of serum of patients suffering from
      breast cancer. Graphical abstract Schematic presentation of a sensitive
      electrochemical immunoassay platform based on ferrocene modified gold
      nanoparticles and lysozyme modified magnetic beads for the determination of alpha
      lactalbumin in human sera and breast milk by the amperometric response of
      ferrocene and hydrogen evolution reaction.

PMID- 30194495
TI  - Anatomical and functional long-term results of endoscopic butterfly inlay
      myringoplasty.
AB  - PURPOSE: The aim of this study was to evaluate the long-term anatomical (graft
      success) and functional (audiological) results of endoscopic butterfly inlay
      myringoplasty. METHODS: The files of 56 patients (29 female, 27 male) who were
      diagnosed with noncomplicated chronic otitis media and underwent endoscopic
      butterfly inlay myringoplasty in 2014-2016 at a tertiary referral center were
      reviewed. Age, gender, follow-up time, perforation location (anterior, posterior
      and central), perforation size (small, medium), pre- and postoperative pure tone
      audiometry (PTA) thresholds, pre- and postoperative air-bone gaps (ABG) and
      complications were noted. RESULTS: Graft success rate was 98.2% in postoperative
      12th month and 94.6% in postoperative 24th month. In all patients, mean PTA for
      air conduction was 35.2 +/- 3.9 dB preoperatively and 27.5 +/- 4.3 dB in
      postoperative 6th month, 25.1 +/- 3.5 dB in postoperative 12th month and 20.4 +/-
      3.2 in postoperative 24th month. Preoperative mean ABG was 24.2 +/- 3.8 dB,
      whereas 19.5 +/- 4.3 dB 6 months after surgery, 17.1 +/- 3.5 dB 12 months after
      surgery and 12.4 +/- 3.1 dB 24 months after surgery. There was significant
      difference between pre- and postoperative PTA and ABG in all 6th, 12th, 24th
      month follow-up (p = 0.001 for all measurements). Three patients (5%) had
      myringitis after surgery. Two patients (3%) had total graft resorption.
      CONCLUSION: We suggested that endoscopic butterfly inlay myringoplasty is a safe
      surgical method with high graft success and effective hearing reconstruction.
      Follow-up is necessary for at least 2 years for precise anatomical and functional
      evaluation of the surgery.

PMID- 30194496
TI  - Comparison of the clinical outcomes of nilotinib and dasatinib therapies in newly
      diagnosed patients in the chronic phase of chronic myeloid leukemia: a
      retrospective analysis.
AB  - Treatment with a tyrosine kinase inhibitor (TKI) is the standard of care for
      patients with chronic myeloid leukemia (CML). The new-generation TKIs, nilotinib
      and dasatinib, are found to have deeper and faster treatment response rates
      compared to imatinib in the first-line setting. However, a direct comparison
      between nilotinib and dasatinib has never been reported previously. Our study
      aims to compare the outcomes and molecular responses achieved following the first
      line use of these two agents in patients with CML-CP. The database of the CML
      Cooperative Study Group was reviewed and patients with CML in the chronic phase
      (CP) who were given nilotinib or dasatinib as first-line therapy were identified.
      Out of 361 patients with CML-CP enrolled in our database, 58 and 63 had been
      treated with conventional doses of nilotinib (300 mg twice daily) and dasatinib
      (100 mg once daily), respectively, as first-line therapy. The patient
      demographics did not show significant differences between the groups. The event
      free survival rates did not differ between these two groups. The major molecular
      response (MMR) and the deep molecular response (DMR) rates by 6, 12, 18, and 24
      months did not differ between groups. Among the three scoring systems, only the
      Hasford score could predict the achievement of DMR, and all of them failed to
      predict the achievement of MMR in the entire cohort. Our data suggest that both
      nilotinib and dasatinib have comparable efficacies and promising outcomes.

PMID- 30194497
TI  - Complications of Botox and their Management.
AB  - PURPOSE OF REVIEW: Adherence to anticholinergic medications is known to be a
      problem in patients with overactive bladder, with only 13.2% of patients
      continuing anticholinergic therapy beyond 1 year D'Souza et al. (J Manag Care
      Pharm. 14:291-301, 2008). RECENT FINDINGS: Prior to the advent of third line
      therapies such as onabotulinumtoxin A, refractory overactive bladder (OAB) was
      managed with augmentation cystoplasty, a lengthy surgery with associated side
      effects including lifetime need for self-catheterization, ileus, and metabolic
      disturbances. The advent of onabotulinumtoxin A has drastically reduced the rates
      of augmentation cystoplasties being performed for refractory OAB. However, all
      procedures are associated with side effects which should be relayed to the
      patient prior to beginning therapy, as well as their management. In the current
      review, we summarize the common complications following onabotulinumtoxin A
      injection as well as their management.

PMID- 30194498
TI  - Computer-Assisted Cognitive-Behavior Therapy in Medical Care Settings.
AB  - PURPOSE OF REVIEW: We reviewed research on computer-assisted cognitive-behavior
      therapy (CCBT) performed in medical settings with the goals of assessing the
      effectiveness of this newer method of treatment delivery, evaluating the need for
      clinician support of therapeutic computer programs, and making suggestions for
      future research and clinical implementation. RECENT FINDINGS: The overall results
      of randomized, controlled trials suggest that CCBT can be an effective treatment
      for depression in primary care patients and health care anxiety. Also, it can be
      a useful component of treatment for somatic conditions including irritable bowel
      syndrome, diabetes, fibromyalgia, and chronic pain. The amount and type of
      clinician support needed for maximizing effectiveness remains unclear. CCBT
      offers promise for overcoming barriers to delivering effective psychotherapy in
      medical settings. We recommend that next steps for researchers include more
      definitive studies of the influence of clinician support, investigations focused
      on implementation in clinical practices, cost-benefit analyses, and use of
      technological advances.

PMID- 30194500
TI  - Equivalent feasibility and safety of perioperative care by ERAS in open and
      laparoscopy-assisted distal gastrectomy for gastric cancer: a single-institution
      ancillary study using the patient cohort enrolled in the JCOG0912 phase III
      trial.
AB  - BACKGROUND: Laparoscopy-assisted distal gastrectomy (LADG) has an advantage of
      earlier recovery after surgery due to having lower invasiveness and wound pain
      than open distal gastrectomy (ODG). However, whether the same enhanced recovery
      after surgery (ERAS) program for LADG is equally feasible and safe for ODG
      remains unclear. METHODS: We retrospectively extracted the clinical data of the
      patients enrolled in JCOG0912 from the medical record system of our hospital and
      compared the treatment process and short-term surgical outcomes between LADG and
      ODG. Our ERAS program consisted of 13 elements (4 preoperative, 4 intraoperative,
      and 5 postoperative elements). The morbidity was defined as complications of
      grade 2 or more. RESULTS: One hundred and sixty-three patients were entered from
      our hospital and randomized to undergo ODG (82 patients) or LADG (81 patients).
      The patient's backgrounds, surgical outcomes, and pathological outcomes were
      similar between the ODG and LADG groups. The rate of completing the clinical
      pathway was 95.1% in both groups, and the rates of completing each ERAS element
      were similar. However, the additional use of acetaminophen was significantly more
      frequent in the ODG group than in the LADG group (18.3% vs. 6.2%, p = 0.03). The
      median hospital stay after surgery was 9 days in both groups. Morbidity, defined
      as Clavien-Dindo classification > grade 2, was observed in 6.1% of the ODG group
      and 11.1% of the LADG group. No mortality occurred in either group. CONCLUSION:
      This study showed that the regimen of perioperative care performed by the ERAS
      program for LADG was equally feasible and safe for ODG with additional pain
      control. Less pain observed in LADG was not so apparent advantage for completion
      and safety of ERAS care.

PMID- 30194499
TI  - Optimal Obstetric Management for Women with Diabetes: the Benefits and Costs of
      Fetal Surveillance.
AB  - PURPOSE OF REVIEW: To elaborate on the risks and benefits associated with
      antenatal fetal surveillance for stillbirth prevention in women with diabetes.
      RECENT FINDINGS: Women with pregestational diabetes have a 3- to 5-fold increased
      odds of stillbirth compared to women without diabetes. The stillbirth risk in
      women with gestational diabetes (GDM) is more controversial; while recent data
      suggest the odds for stillbirth are approximately 50% higher in women with GDM at
      term (37 weeks and beyond) than in those without GDM, it is unclear if this risk
      is seen in women with optimal glycemic control. Current professional society
      guidelines are broad with respect to fetal testing strategies and delivery timing
      in women with diabetes. The data supporting strategies to reduce the risk of
      stillbirth in women with diabetes are limited. Antepartum fetal surveillance
      should be performed to reduce stillbirth rates; however, the optimal test,
      frequency of testing, and delivery timing are not yet clear. Future studies of
      obstetric management for women with diabetes should consider not just individual
      but also system level costs and benefits associated with antenatal surveillance.

PMID- 30194501
TI  - [The patient blood group-the small but important difference].

PMID- 30194502
TI  - Project Nova: A Combination HIV Prevention and Microfinance Intervention for
      Women Who Engage in Sex Work and Use Drugs in Kazakhstan.
AB  - Innovative combination HIV-prevention and microfinance interventions are needed
      to address the high incidence of HIV and other STIs among women who use drugs.
      Project Nova is a cluster-randomized, controlled trial for drug-using female sex
      workers in two cities in Kazakhstan. The intervention was adapted from prior
      interventions for women at high risk for HIV and tailored to meet the needs of
      female sex workers who use injection or noninjection drugs. We describe the
      development and implementation of the Nova intervention and detail its
      components: HIV-risk reduction, financial-literacy training, vocational training,
      and a matched-savings program. We discuss session-attendance rates, barriers to
      engagement, challenges that arose during the sessions, and the solutions
      implemented. Our findings show that it is feasible to implement a combination HIV
      prevention and microfinance intervention with highly vulnerable women such as
      these, and to address implementation challenges successfully.

PMID- 30194503
TI  - Identification of unique glycoisoforms of vitamin D-binding protein and
      haptoglobin as biomarker candidates in hepatocarcinogenesis of STAM mice.
AB  - Hepatocellular carcinoma (HCC) is the major subtype of primary liver cancer, and
      is typically diagnosed late in its course. Considering the limitations and the
      reluctance of patients to undergo a liver biopsy, a reliable, noninvasive
      diagnostic marker that predicts and assesses the treatment and prognosis of HCC
      is needed. With recent technological advances of mass spectrometry, glycomics is
      gathering momentum and holds substantial potential to discover new glycan markers
      in cancer research. Here, to discover specific glycan markers for the early
      diagnosis of HCC, we analyzed the glycan profiles of gel-separated serum proteins
      of progressive liver disease model mice. By focused protein glycomics of 12 gel
      separated glycoproteins using sera from the mouse models, we revealed the entire
      profile of glycans in each major serum protein. We found that the levels of
      trisialylated triantennary glycans of haptoglobin and vitamin D-binding protein
      increased significantly as the disease progressed, while the alteration in these
      protein levels were modest. Furthermore, these glycan increases were not observed
      in age-matched control mice. In conclusion, our approach has identified specific
      glycan marker candidates for the early diagnosis of HCC.

PMID- 30194504
TI  - Ruegeria sp. Strains Isolated from the Reef-Building Coral Galaxea fascicularis
      Inhibit Growth of the Temperature-Dependent Pathogen Vibrio coralliilyticus.
AB  - The coral microbiome has attracted increased attention because of its potential
      roles in host protection against deadly diseases. However, little is known about
      the role of coral-associated bacteria against the temperature-dependent
      opportunistic pathogen Vibrio coralliilyticus. In this study, we tested whether
      bacteria associated with the reef-building coral Galaxea fascicularis could
      inhibit the growth of V. coralliilyticus. Twenty-nine cultivable bacteria were
      successfully isolated from a healthy colony of G. fascicularis kept in an
      aquarium. Among the bacterial isolates, three Ruegeria sp. strains inhibited the
      growth of V. coralliilyticus P1 as a reference strain and Vibrio sp. isolated in
      this study. Ruegeria sp. strains were also detected from other G. fascicularis
      colonies in the aquarium and in previous field studies by 16S rRNA amplicon
      sequencing, suggesting that Ruegeria sp. strains are common among G. fascicularis
      colonies. These results illuminate the potential role of Ruegeria sp. in
      protecting corals against pathogenic Vibrio species.

PMID- 30194505
TI  - Carboxytherapy-Induced Fat loss is Associated with VEGF-Mediated Vascularization.
AB  - BACKGROUND: Carboxytherapy is the transcutaneous administration of CO2 gas for
      therapeutic purposes. Although this non-surgical procedure has been widely used
      for reducing localized adiposity, its effectiveness on fat loss in obese patients
      and its underlying mechanisms remain unclear. METHODS: C57BL/6 mice were fed with
      a high-fat diet for 8 weeks to generate obese animal models. Obese mice were
      randomly assigned to two groups: One group was administered air to both inguinal
      fat pads (air/air), and the other group was treated with air to the left inguinal
      fat pad and with CO2 to the right inguinal fat pad (air/CO2). Each group was
      treated every other day for 2 weeks. Morphological changes and expression levels
      of genes associated with lipogenesis and vascularization in fat were determined
      by histological and qRT-PCR analyses. RESULTS: Mice treated with air/CO2 showed
      lower body weights and blood glucose levels compared to air/air-treated mice.
      Paired comparison analysis revealed that CO2 administration significantly
      decreased adipose tissue weights and adipocyte sizes compared to air treatment.
      Additionally, CO2 treatment markedly increased vessel numbers and expressions of
      Vegfa and Fgf1 genes in adipose tissues. The expressions of Fasn and Fabp4 genes
      were also modestly reduced in CO2-treated adipose tissue. Moreover, Ucp1
      expression, the target gene of VEGF and a key regulator in energy expenditure,
      was significantly increased in CO2-treated adipose tissue. CONCLUSIONS:
      Carboxytherapy is effective in the reduction of localized fat in obese patients
      which is mechanistically associated with alteration of the vasculature involved
      in VEGF. 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- 30194506
TI  - Exploitation of new endophytic bacteria and their ability to promote sugarcane
      growth and nitrogen nutrition.
AB  - Few studies have evaluated endophytic bacteria in relation to plant growth
      promotion, nitrogen uptake and biological control. The aim of this study was to
      molecularly and physiologically characterize thirteen endophytic bacteria
      strains, evaluate their biological control properties and their ability to
      promote plant growth and plant N nutrition. All the strains produced indole
      acetic acid and promoted increase of plant biomass, N accumulative amount and N
      use efficiency index. None of the strains carries the nifH gene. Four strains
      stimulated plant nitrate reductase activity, four solubilized phosphate, nine
      produced siderophores and none produced HCN. Seven strains inhibited Bipolaris
      sacchari growth and one was antagonistic to Ceratocystis paradoxa. The pathogens
      were inhibited by the production of diffusible and volatile metabolites by the
      bacterial strains. Moreover, this is the first study to demonstrate the effect of
      Delftia acidovorans on sugarcane plant growth, nitrogen metabolism improvement
      and antagonism to B. sacchari. The most efficient strains in promoting plant
      growth and exhibiting antagonistic activities towards fungal pathogens were
      Herbaspirillum frinsingense (IAC-BECa-152) and three Pantoea dispersa strains
      (IAC-BECa-128, IAC-BECa-129, and IAC-BECa-132). These bacteria show potential to
      be used as inoculants for sustainable agricultural management, mainly at the
      seedling production phase.

PMID- 30194507
TI  - Intracellular calcite and sulfur dynamics of Achromatium cells observed in a lab
      based enrichment and aerobic incubation experiment.
AB  - We investigated the intracellular dynamics of calcite and sulfur in the large
      sulfur-oxidizing, calcite-accumulating bacterium Achromatium, with an emphasis on
      oxygen exposure as a physiological control. For this purpose, morphological
      changes and possible accretion mechanisms of calcite granules in cells that were
      freshly collected from natural Achromatium-containing sediment were compared to
      cells from the same source after prolonged exposure to atmospheric oxygen.
      Intracellular sulfur is oxidized and removed in response to oxygen exposure.
      Calcite granules also undergo distinct oxygen-related dynamics; they alternate
      between tightly packaged, smooth granules with narrow but sharply defined
      interstitial spaces in atmospheric oxygen-exposed cells, and more loosely
      packaged granules with irregular, bumpy surface texture and larger interstitial
      spaces in cells that were not artificially exposed to oxygen. These results
      suggest that morphological changes of the calcite granules reflect their changing
      physiological role inside the cell. Sulfur oxidation and calcite dissolution
      appear to be linked in that proton generation during sulfur oxidation is buffered
      by gradual calcite erosion, visible in the smooth, rounded surface morphology
      observed after oxygen exposure. Our results support the hypothesis that calcite
      dynamics buffer the intracellular pH fluctuations linked to electron acceptor
      limitation during proton-consuming sulfide oxidation to sulfur, and electron
      acceptor abundance during proton-generating sulfur oxidation to sulfate.

PMID- 30194509
TI  - A Multi-Fidelity Rollout Algorithm for Dynamic Resource Allocation in Population
      Disease Management.
AB  - Dynamic resource allocation for prevention, screening, and treatment
      interventions in population disease management has received much attention in
      recent years due to excessive healthcare costs. In this paper, our goal is to
      design a model and an efficient algorithm to optimize sequential intervention
      policies under resource constraints to improve population health outcomes. We
      consider a discrete-time finite-horizon budget allocation problem with disease
      progression within a closed birth-cohort population. To address the computational
      challenges associated with large-state and multiple-period dynamic decision
      making problems, we propose a low-fidelity approximation that preserves the
      population dynamics under a stationary policy. To improve the healthcare
      interventions in terms of population health outcomes, we then embed the low
      fidelity approximation into a high-fidelity optimization model to efficiently
      identify a good non-stationary sequential intervention policy. Our approach is
      illustrated by a numerical example of screening and treatment policy
      implementation for chronic hepatitis C virus (HCV) infection over a budget
      planning period. We numerically compare our Multi-Fidelity Rollout Algorithm (MF
      RA) to a grid search approach and demonstrate the similarity of sequential policy
      trends and closeness of overall health outcomes measured by quality-adjusted life
      years (QALYs) and the total number of individuals that undergo screening and
      treatment for different annual budgets and birth-cohorts. We also show how our
      approach scales well to problems with high dimensionality due to many decision
      periods by studying time to elimination of HCV.

PMID- 30194508
TI  - Association of Child Maltreatment with South African Adults' Wages: Evidence from
      the Cape Area Panel Study.
AB  - Child maltreatment is a prevalent public health problem in both developed and
      developing countries. While many studies have investigated the relationship
      between violence against children and health of the victims, little is known
      about the long term economic consequences of child maltreatment, especially in
      developing countries. Using data from the Cape Area Panel Study, this paper
      applies Heckman selection models to investigate the relationship between
      childhood maltreatment and young adults' wages in South Africa. The results show
      that, on average, any experience of physical or emotional abuse during childhood
      is associated with a later 12% loss of young adults' wages. In addition, the
      correlation between physical abuse and economic consequence (14%) is more
      significant than the relationship between emotional abuse and wages (8%) of young
      adults; and the higher the frequency of maltreatment, the greater the
      associations with wages. With respect to gender differences, wage loss due to the
      experience of childhood maltreatment is larger for females than males.
      Specifically, males' wages are more sensitive to childhood emotional abuse, while
      females' wages are more likely to be affected by childhood physical abuse. These
      results emphasize the importance of prioritizing investments in prevention and
      intervention programs to reduce the prevalence of child maltreatment and to help
      victims better overcome the long-term negative effect.

PMID- 30194510
TI  - Sperm quality analysis of normal season (NG) and out-season by photoperiod
      manipulation (PG) of male rainbow trout broodstock (Oncorhynchus mykiss).
AB  - Sperm quality parameters in rainbow trout (Oncorhynchus mykiss) were investigated
      during normal season spawning (November-January) and out-season spawning (July
      August) treated with artificial photoperiod manipulation. Normal spawning males
      (n = 15) were kept in an open concrete pond under natural condition. Out-season
      spawning males (n = 15) were treated with artificial LED light (50 lm/m2) in a
      closed concrete pond. In these two experimental groups, five fish were used in
      each of three spawning periods. The mean weight and body length of males (2 +
      years, n = 30) were 1213.43 +/- 39.43 g and 45.08 +/- 0.62 cm, respectively.
      Sperms were collected from July to August 2016 in the out-season spawning or
      photoperiod-manipulated group (PG) (water temperature 14.21 +/- 0.31  degrees C)
      and from December 2016 to January 2017, in the normal season spawning group (NG)
      (water temperature 8.81 +/- 1.03  degrees C). Volume of sperm, osmolality of
      seminal plasma, density of sperm, percentage of motile spermatozoa (MOT),
      curvilinear velocity (VCL), and duration of motility were measured for each male.
      Seminal plasma osmolality, density of sperm, and the motility of duration were
      358.47 +/- 37.24 and 308.87 +/- 44.09, 4.37 +/- 2.10 and 9.8 +/- 1.56, and 8.8 +/
      2.42 and 24.6 +/- 6.76 in PG and NG, respectively. Fertilization rate was 37.79
      +/- 9.37% and 94.51 +/- 1.33% in PG and NG, respectively. Sperm quality
      parameters showed significant differences in most of the cases (p < 0.05) and
      fertilization rate at eyed egg stage (150-160 degree-days) was significantly
      higher in normal season spawning group than the photoperiod-manipulated group (p
      < 0.05). Though the rate of fertilization was low in out-season, it was able to
      get enough gametes in summer using only artificial light having no changes in
      other parameters.

PMID- 30194511
TI  - Prediction of postoperative disease-free survival and brain metastasis for HER2
      positive breast cancer patients treated with neoadjuvant chemotherapy plus
      trastuzumab using a machine learning algorithm.
AB  - PURPOSE: This study aimed to develop mathematical tools to predict the likelihood
      of recurrence after neoadjuvant chemotherapy (NAC) plus trastuzumab in patients
      with human epidermal growth factor receptor 2 (HER2)-positive breast cancer.
      METHODS: Data of 776 patients from a multicenter retrospective cohort study were
      collected. All patients had HER2-positive breast cancer and received NAC plus
      trastuzumab between 2001 and 2010. Two mathematical tools using a machine
      learning method were developed to predict the likelihood of disease-free survival
      (DFS) (DFS model) and brain metastasis (BM) (BM model) within 5 years after
      surgery. For validation, bootstrap analyses were conducted. The area under the
      receiver operating characteristics curve (AUC) was calculated to examine the
      discrimination. RESULTS: The AUC values were 0.785 (95% CI 0.740-0.831, P <
      0.001) for the DFS model and 0.871 (95% CI 0.830-0.912, P < 0.001) for the BM
      model. Patients with low-risk DFS or BM events, as predicted by the models,
      showed better 5-year DFS and BM rates than those with high-risk DFS or BM events
      (89% vs. 61% for the DFS model, P < 0.001; 99% vs. 87% for the BM model, P <
      0.001). These models maintained discrimination abilities in both luminal and non
      luminal subtypes, providing prognostic information independent of pathological
      response. Bootstrap validation confirmed the high generalization abilities of the
      models. CONCLUSIONS: The DFS and BM models have a high accuracy to predict
      prognosis among HER2-positive patients treated with NAC plus trastuzumab. Our
      models can help optimize adjuvant therapy and postoperative surveillance.

PMID- 30194512
TI  - A complete posterior tibial stress fracture that occurred during a middle
      distance running race: a case report.
AB  - Posterior tibial stress fractures are more frequent than anterior tibial stress
      fractures, and they are considered to have a good prognosis for returning to
      sports; cases leading to a complete fracture are rare. A 17-year-old male
      involved in high school athletics middle-distance running had a 3-week history of
      pain with training. He was running up to 300 km/week on streets and cross-country
      in an even distribution. He had posterior tibial stress fractures, but despite
      the lower leg pain, he continued running. One year later, he was brought to the
      emergency department after having sustained an injury to the right lower leg
      while running in a middle-distance race; bilateral tibial stress fractures, with
      one side complete and the opposite side incomplete, had developed simultaneously.
      This relatively rare case of bilateral posterior stress fractures, with one side
      a complete fracture and the opposite side an incomplete fracture, that was
      treated surgically via exchange intramedullary nailing is reported. The patient
      could begin light jogging from 3 months after surgery and was without symptoms at
      5 months after surgery. He could resume middle-distance racing after 1 year.
      Posterior tibial cortical fractures are more common and respond better to
      conservative treatment than anterior tibial stress fractures, and they are a
      common fracture type in runners. We believe that close, careful follow-up is
      necessary if patients continue excessive training.

PMID- 30194513
TI  - Professional ethics: the case of neonatology.
AB  - Neonatal professionals encounter many ethical challenges especially when it comes
      to interventions at the limit of viability (weeks 22-25 of gestation). At times,
      these challenges make the moral dilemmas in neonatology tragic and they require a
      particular set of intellectual and moral virtues. Intellectual virtues of
      episteme and phronesis, together with moral virtues of courage, compassion,
      keeping fidelity to trust, and integrity were highlighted as key virtues of the
      neonatal professional. Recognition of the role of ethics requires a recognition
      that answering the obvious question (what shall we do?) does not always suffice.
      Acknowledging the tragic question (is any of the alternatives open to us free
      from serious moral wrongdoing) and recognizing the ethical dilemmas, where the
      lines between right and wrong are blurred, leads to actions taken towards
      establishing ethics frameworks to support decision-making. In neonatology units,
      such organizational support can help in allowing the team members to recognize
      the ethical dilemmas, avoid moral distress, and improve team cohesion and the
      quality of care provided. Only when the organizational structure allows ethical
      dilemmas to be recognized, adequate decisions can be made.

PMID- 30194514
TI  - Overexpression of filamin c in chronic intermittent hypoxia-induced cardiomyocyte
      apoptosis is a potential cardioprotective target for obstructive sleep apnea.
AB  - PURPOSE: Chronic intermittent hypoxia (CIH) is key pathological mechanism of
      obstructive sleep apnea (OSA), which induced cardiac dysfunction. Filamin c
      (FLNC) is a muscle-restricted isoform and predominantly expressed in muscle
      tissue. In this study, we utilized a recently developed CIH rat model to mimic
      OSA, investigated the expression of FLNC in cardiomyocytes, and examined the
      correlations of FLNC with active caspase-3 to ascertain whether FLNC regulates
      the survival of cardiomyocytes. METHODS: Forty Sprague-Dawley rats were randomly
      divided into normoxia and CIH groups. All rats were exposed either to normoxia or
      CIH 8 h daily for 6 weeks. Echocardiogram and HE staining were used to examine
      cardiac pathology, structure, and function. Body weight, heart weight, and blood
      gas values were recorded, respectively. The FLNC, Bax, Bcl-2, BNIP 3, and active
      caspase-3 proteins were detected by western blot; FLNC was examined by
      immunohistochemistry and immunofluorescence. Association of FLNC with
      cardiomyocyte apoptosis was detected by immunofluorescence. RESULTS: CIH induced
      cardiac injuries and caused arterial blood gas disorder. FLNC significantly
      increased in CIH-induced cardiomyocytes than that in normoxia tissues. Pro
      apoptotic BNIP 3 and Bax proteins were significantly increased in CIH, whereas
      anti-apoptotic member Bcl-2 was decreased. Active caspase-3, a universal marker
      of apoptosis, was significantly increased in CIH group. Co-localizations of FLNC
      and active caspase-3 were observed in CIH group. CONCLUSIONS: These results
      suggested FLNC is implicated in the pathogenesis of CIH-induced cardiomyocyte
      apoptosis, and FLNC may serve as a novel cardioprotective target for OSA
      patients.

PMID- 30194515
TI  - The concept of strongly interacting groups in self-assembly of soft matter.
AB  - Amphiphilic molecules in solution typically produce structures coming from
      cooperative interactions of many synergetically acting functional units. If all
      essential interactions are weak, the structure can be treated theoretically based
      on a free energy expansion for small interaction parameters. However, most self
      assembling soft matter systems involve strong specific interactions of functional
      units leading to qualitatively new structures of highly soluble micellar or
      fibrillar aggregates. Here we focus on the systems with the so-called strongly
      interacting groups (SIGs) incorporated into unimer molecules and discuss the
      effects of packing frustrations and unimer chirality as well as the origins of
      spontaneous morphological chirality in the case of achiral unimers. We describe
      several theoretical approaches (overcoming the limitations of weak interaction
      models) including the concepts of super-strong segregation, geometrical mismatch
      and orientational frustration. We also review some recently developed
      phenomenological theories of surfactant membranes and multiscale hierarchical
      approaches based on all-atomic modeling of packing structures of amphiphilic
      molecules with SIGs. In particular, we discuss self-assembling structures in
      systems possessing simultaneously several distinct types of SIGs: solutions of
      beta-sheet oligopeptides (showing different fibrillar morphologies), aromatic
      diamide-ester molecules (forming membranes, helical ribbons and tubules), and
      triarylamine amide derivatives (producing light-controlled supramolecular
      nanowires).

PMID- 30194516
TI  - Loop diuretics in chronic heart failure: how to manage congestion?
AB  - Loop diuretics remain the cornerstone of congestion management in contemporary
      chronic heart failure care. However, their use is not supported by high quality
      data, and there is doubt about the safety in the outpatient heart failure
      setting. Still, congestion is related to a worse outcome, and there is general
      consensus among experts that congestion should not be tolerated in heart failure
      patients. Recommendations in international guidelines, regarding decongestion
      strategies in chronic heart failure, are limited. Thus, there is an emerging need
      for clinical decision-making support about the best strategy for using loop
      diuretics and decongestion in the chronic setting. The present review provides a
      comprehensive overview over the evidence of chronic loop diuretic use. Strategies
      for the assessment of congestion in the outpatient setting and decongestion
      algorithm are provided to assist health care specialists in delivering high
      quality heart failure care.

PMID- 30194517
TI  - Early Behavioral Alterations and Increased Expression of Endogenous Retroviruses
      Are Inherited Across Generations in Mice Prenatally Exposed to Valproic Acid.
AB  - Prenatal treatment with the antiepileptic drug valproic acid (VPA) is associated
      with a significant risk of somatic anomalies, neurodevelopmental delays, and 7
      10* increase in the incidence of autism spectrum disorders (ASD) in children.
      Rodents exposed to VPA in pregnancy show birth defects, deficits in
      neurodevelopment, and cognitive/social anomalies resembling those of ASD
      children. Mechanisms of VPA neurobehavioral toxicity are still unclear but as VPA
      is a non-selective inhibitor of histone deacetylases, epigenetic modifications
      are likely involved. This study was aimed to evaluate the transgenerational
      impact of prenatal VPA exposure on mouse early behavioral development, studying
      F1, F2, and F3 generations after VPA challenge on gestational day (GD) 10.5. We
      also analyzed in brain and in peripheral blood mononuclear cells the expression
      levels of different endogenous retrovirus (ERV) families, potential biomarkers of
      derailed brain development, since human ERVs have been implicated in the
      pathogenesis of neurodevelopmental disorders (NDDs) such as ASD. Somatic effects
      of VPA were evident only in F1 generation and more markedly in the female sex.
      Across F1 and F2 generations, VPA delayed righting reflex, increased motor
      activity, and reduced ultrasonic vocalizations. The behavioral changes in F3 are
      milder though in the same direction. VPA increased expression of most ERVs across
      the three generations in brain and blood. In utero VPA induced neurodevelopmental
      alterations more marked in the maternal lineage that persisted also in F3,
      suggesting ERVs as possible downstream effectors of the VPA epigenetic
      alterations.

PMID- 30194518
TI  - Psychosocial Determinants of Teens' Online Engagement in Drug Prevention Social
      Media Campaigns: Implications for Public Health Organizations.
AB  - Social networking sites (SNSs) now serve as a primary form of communication among
      adolescents. Consequently, drug prevention campaigns delivered through SNSs have
      the potential to reach a wide network of adolescents if teens are willing to
      engage in the message diffusion process by commenting on, "liking," following,
      creating, or sharing prevention messages with their networked peers. However,
      little is known about the psychosocial factors that influence adolescents'
      willingness to participate in drug prevention social media campaigns. We use
      qualitative methods to explore reasons why adolescents may or may not want to
      engage in the message diffusion process. We conducted four semi-structured focus
      groups with a total of 33 high school students from various school- and community
      based youth programs in Rhode Island. Focus groups were followed by a brief self
      administered questionnaire collecting information about participants' social
      media use to augment qualitative findings. Overall, findings reveal that engaging
      teens in the message diffusion process can be advantageous but difficult to
      accomplish due to multiple factors. Most notably, asking adolescents to
      participate in drug prevention campaigns delivered through SNSs means also asking
      youth to violate online norms that promote drug use, which could in turn subject
      them to peer reprisal. We conclude that future studies should begin to
      investigate strategies addressing the various challenges we identified.
      Meanwhile, prevention specialists should consider alternative or supplemental
      evidence-based approaches to drug prevention rather than invest resources into
      activities that may offer little return on investment.

PMID- 30194519
TI  - Community Health and Employee Work Performance in the American Manufacturing
      Environment.
AB  - Although better community health has long been assumed to be good for local
      businesses, evidence demonstrating the relationship between community health and
      employee performance is quite limited. Drawing on human resources data on 6103
      employees from four large US manufacturing plants, we found that employees living
      in counties with poor community health outcomes had considerably higher rates of
      absenteeism and tardiness (ABT). For example, in one company, employees living in
      communities with high rates of children on free or reduced lunch had higher rates
      of ABT compared to other employees [adjusted odds ratio (OR) 2.76, 95% confidence
      interval (CI) 2.52-3.04], and employees living in communities with high rates of
      drug overdose deaths had higher rates of ABT (OR 1.51, 95% CI 1.29-1.77). In one
      plant, the annual value of lost wages due to ABT was over $1.3 million per year.
      Employees reported that poor community health (e.g., poverty, caregiving burdens,
      family dysfunction, drug use) resulted in "mental stress" leading to distraction,
      poor job performance, and more rarely, lapses in safety. These findings bolster
      the case for greater private sector investment in community health.

PMID- 30194520
TI  - Effect of an Acute Exercise Until Exhaustion on the Serum and Urinary
      Concentrations of Cobalt, Copper, and Manganese Among Well-Trained Athletes.
AB  - The current information about the effect of physical exercise on the body
      concentrations of several minerals is still limited, both in the acute (short
      term) and adaptive (long-term) responses. So, this manuscript aims, on the one
      hand, to assess the possible differences on basal levels of cobalt (Co), copper
      (Cu), and manganese (Mn) concentrations in serum and urine between athletes and
      sedentary participants and, on the other hand, to evaluate the effect of an acute
      progressive physical exercise until voluntary exhaustion on the serum and urinary
      concentrations of Co, Cu, and Mn. Two groups participated in this survey, one was
      formed by untrained, sedentary males (CG; n = 26), and the other group was
      constituted by national endurance (long and middle distances) athletes (AG; n =
      21). All participants were from the same region of Spain. Participants of both
      groups performed a physical test on a treadmill, reaching voluntary exhaustion.
      Blood and urine samples of each participant were collected before and at after
      the tests. Once obtained and processed, the concentrations of Co, Cu, and Mn
      elements were analyzed by inductively coupled plasma mass spectrometry (ICP-MS).
      The differences in the studied variables were evaluated using a mixed model by
      means of an ANOVA and Bonferroni post hoc tests. In the comparison of the pre
      test values between groups, the results showed that serum concentrations of Mn
      were significantly lower in CG than in AG (p < 0.01). In urine, Co and Mn levels
      were significantly higher among CG participants (p < 0.01) than among AG ones,
      while in the case of Cu, the values were lower (p < 0.01) in the CG than in the
      AG. Regarding the effects of the effort tests, no significant changes were found
      among the participants of the CG. It was observed that the serum concentrations
      of Co (p < 0.05) and Cu (p < 0.01) decreased after the test among the AG
      participants. Also, the results showed that there were no statistical differences
      in Co and Mn values (expressed in MUg/g creatinine). However, the urinary post
      test Cu concentrations were lower (p < 0.05) among AG participants. In basal
      conditions, serum concentrations of Mn were significantly lower in CG than in AG.
      In urine, Co and Mn levels were significantly higher among CG participants and Cu
      level was significantly lower in CG, a fact which may reflect adaptive responses
      to exercise. An incremental exercise to exhaustion in AG produces a decrease in
      Co and Cu serum concentrations, as well as in urinary excretion of Cu.

PMID- 30194521
TI  - CaVIL1, a plant homeodomain gene that promotes flowering in pepper.
AB  - KEY MESSAGE: CaVIL1 is a homolog of VIL1, a regulator of vernalization response
      in Arabidopsis and acts as a flowering promoter in pepper which does not respond
      to vernalization and photoperiod. As part of our goal to study the genetic and
      molecular basis of transition to flowering in pepper, we isolated the late
      flowering mutant E-2698. Aside from late flowering, multiple pleiotropic
      alterations of the shoot structure, such as enlarged and distorted leaves, weak
      apical dominance, and reduced angle of the lateral branches were observed,
      indicating a broad role for the mutated gene in pepper development. Genetic
      mapping and sequence analyses revealed that the disrupted gene in E-2698 is the
      pepper homolog of VERNALIZATION INSENSITIVE 3-LIKE 1 (VIL1) that acts as a
      regulator of vernalization in Arabidopsis through chromatin modification. The
      pepper gene, CaVIL1, contains a plant homeodomain motif associated with chromatin
      modification and a VERNALIZATION INSENSITIVE 3-interacting domain that is
      truncated in E-2698 and in two other allelic mutants. Because pepper flowering
      does not respond to vernalization, we postulate that CaVIL1 regulates flowering
      time via chromatin modification of unknown targets. Expression analysis indicated
      that CaVIL1 activates the flowering promoter CaFLOWERING LOCUS T and represses
      the flowering repressor CaAPETALA2. Furthermore, CaVIL1 represses several genes
      from the FLOWERING LOCUS C (FLC)-LIKE clade that are clustered together in the
      pepper genome. This indicates their possible involvement in flowering regulation
      in this species. Our results show that CaVIL1 is a major regulator of flowering
      and interacts with other flowering promoters and repressors, as well as with FLC
      LIKE genes whose function in flowering regulation is not yet known in pepper.

PMID- 30194522
TI  - Multifractal Characterization of Butterfly Wings Scales.
AB  - A lot of insect families have physical structures created by evolution for
      coloration. These structures are a source of ideas for new bio-inspired
      materials. The aim of this study was to quantitatively characterize the
      micromorphology of butterfly wings scales using atomic force microscopy and
      multifractal analysis. Two types of butterflies, Euploea mulciber ("striped blue
      crow") and Morpho didius ("giant blue morpho"), were studied. The three
      dimensional (3D) surface texture of the butterfly wings scales was investigated
      focusing on two areas: where the perceived colors strongly depend on and where
      they do not depend on the viewing angle. The results highlight a correlation
      between the surface coloration and 3D surface microtexture of butterfly wings
      scales.

PMID- 30194523
TI  - The Crisis of Reproducibility, the Denominator Problem and the Scientific Role of
      Multi-scale Modeling.
AB  - The "Crisis of Reproducibility" has received considerable attention both within
      the scientific community and without. While factors associated with scientific
      culture and practical practice are most often invoked, I propose that the Crisis
      of Reproducibility is ultimately a failure of generalization with a fundamental
      scientific basis in the methods used for biomedical research. The Denominator
      Problem describes how limitations intrinsic to the two primary approaches of
      biomedical research, clinical studies and preclinical experimental biology, lead
      to an inability to effectively characterize the full extent of biological
      heterogeneity, which compromises the task of generalizing acquired knowledge.
      Drawing on the example of the unifying role of theory in the physical sciences, I
      propose that multi-scale mathematical and dynamic computational models, when
      mapped to the modular structure of biological systems, can serve a unifying role
      as formal representations of what is conserved and similar from one biological
      context to another. This ability to explicitly describe the generation of
      heterogeneity from similarity addresses the Denominator Problem and provides a
      scientific response to the Crisis of Reproducibility.

PMID- 30194524
TI  - Epidemics in Competition: Partial Cross-Immunity.
AB  - The competition between two pathogen strains during the course of an epidemic
      represents a fundamental step in the early evolution of emerging diseases as well
      as in the antigenic drift process of influenza. The outcome of the competition,
      however, depends not only on the epidemic properties of the two strains but also
      on the timing and size of the introduction, characteristics that are poorly
      captured by deterministic mean-field epidemic models. We describe those aspects
      of the competition that can be determined from the mean-field models giving the
      range of possible final sizes of susceptible hosts and cumulated attack rates
      that could be observed after an epidemic with two cross-reacting strains. In the
      limit where the size of the initial infection goes to zero, the possible outcomes
      lie on a (one dimensional) curve in the outcome space.

PMID- 30194526
TI  - Comment to: "A simple prognostic index for Shigatoxin-related hemolytic uremic
      syndrome at onset: data from the ItalKid-HUS network" by Ardissino et al. Eur J
      Pediatr. 2018 Aug 10. doi: 10.1007/s00431-018-3198-7.

PMID- 30194525
TI  - Renal Replacement Therapy in children with severe developmental disability:
      guiding questions for decision-making.
AB  - Whether to initiate or to withhold Renal Replacement Therapy (RRT) in children
      with severe developmental disability (DD) remains a topic of intense debate. The
      present study investigated the opinion of professionals on this difficult issue
      and proposed a checklist with guiding questions for decision-making. Clinicians
      affiliated to different organizations involved in pediatric nephrology worldwide
      were invited to respond to a web-based survey. This survey focused on the
      collection of demographic data of the respondents together with their opinion
      concerning the decision-making regarding RRT in a particular case and for
      children with severe DD in general. A total of 286 professionals responded to the
      survey. Sixty-six percent supported initiating RRT in the child of the case
      report, with pre-emptive transplantation being the preferred modality. Important
      arguments pro RRT initiation in children with severe DD in general were parental
      preference, decrease of suffering, and improvement of survival and quality of
      life. Important contraindications included low IQ, severe comorbidities, and
      inability of the patient to take medication or for the family to provide
      sufficient care.Conclusion: The present study presents an inventory on the
      opinions of health care professionals involved in RRT in children regarding the
      treatment of children with DD and assists in the decision-making process by
      identifying important medical and psychosocial arguments for initiating or
      withholding RRT in severe DD patients. What is Known: *Renal Replacement Therapy
      (RRT) in children with severe developmental disability (DD) is a topic of intense
      debate. *Previous studies on the opinion of professionals mainly focused on the
      use of IQ as an argument in the decision-making whether or not starting RRT. What
      is New: *The present study investigated the opinion of professionals with regard
      to considering initiation or withholding RRT in children with severe DD and
      identified medical and psychosocial arguments playing a role in the decision
      making process. *Based on these arguments, a checklist with guiding questions for
      decision-making is proposed.

PMID- 30194528
TI  - Overcoming transporter-mediated multidrug resistance in cancer: failures and
      achievements of the last decades.
AB  - Multidrug resistance (MDR) is a complex phenomenon caused by numerous reasons in
      cancer chemotherapy. It is related to the abnormal tumor metabolism, precisely
      increased glycolysis and lactic acid production, extracellular acidification, and
      drug efflux caused by transport proteins. There are few strategies to increase
      drug delivery into cancer cells. One of them is the inhibition of carbonic
      anhydrases or certain proton transporters that increase extracellular acidity by
      proton extrusion from the cells. This prevents weakly basic chemotherapeutic
      drugs from ionization and increases their penetration through the cancer cell
      membrane. Another approach is the inhibition of MDR proteins that pump the
      anticancer agents into the extracellular milieu and decrease their intracellular
      concentration. Physical methods, such as ultrasound-mediated sonoporation, are
      being developed, as well. To increase the efficacy of sonoporation, various
      microbubbles are used. Ultrasound causes microbubble cavitation, i.e., periodical
      pulsation of the microbubble, and destruction which results in formation of
      temporary pores in the cellular membrane and increased permeabilization to drug
      molecules. This review summarizes the main approaches to reverse MDR related to
      the drug penetration along with its applications in preclinical and clinical
      studies.

PMID- 30194527
TI  - Subclinical myocardial injury during vaso-occlusive crisis in pediatric sickle
      cell disease.
AB  - Acute painful crisis is the most frequent complication of sickle cell disease
      (SCD) in children. Recurrent vaso-occlusion may be associated with cardiac
      injury. The study aimed to assess silent myocardial injuries for sickle cell
      children during acute painful crisis by measuring serum level of troponin I and
      galectin-3. The study included 87 participates; study group (n = 44) sickle cell
      children presented at Jeddah hospitals in Saudi Arabia by painful crisis or acute
      illness as fever or cough (2017-2018). The controls were healthy children (n =
      43). Demographic and history data were collected from the cases. Troponin I and
      galectin-3 were measured. Galectin-3 values were higher among cases with
      significant difference when compared to controls (7.5 +/- 3.1 versus 3.2 +/- 1.6,
      < 0.001). Galectin-3 at a cutoff > 5.1 ng/ml, the sensitivity was 88.64 and
      specificity was 88.37. Galectin-3 levels were higher for the pain crisis subgroup
      in comparison to acute illness group with significant difference (r 0.551*, p <
      0.001*). Galectin-3 values were higher among troponin-positive cases with
      significant difference (p = 0.046) to troponin-negative cases.Conclusion:
      Positive results of troponin I and high levels of galectin-3 in sickle cell
      children during acute painful crisis were potent indicators for subclinical
      myocardial injury. What is Known: * The hallmark of sickle cell disease is
      recurrent episodes of vaso-occlusive crisis which had deleterious effects on many
      organs. * Cardiac changes in pediatric sickle cell disease whether structural or
      functional are mainly attributed to chronic anemia and or pulmonary hypertension.
      What is New: * The observed positive results of cardiac troponin I and high
      values of galectin-3 in sickle cell children during vaso-occlusive crisis are
      strong indicator of myocardial ischemia and ongoing cardiac fibrosis
      respectively. * The observed correlation between biological markers (positive
      troponin and high galectin-3) could be an indication of subclinical cardiac
      injury.

PMID- 30194529
TI  - Cervical and postural strategies for maintaining horizontal gaze in asymptomatic
      adults.
AB  - PURPOSE: To investigate the different cervical strategies for maintaining
      horizontal gaze in asymptomatic subjects. METHODS: One hundred and forty-four
      asymptomatic adults filled the SF-36 quality of life questionnaire and underwent
      full-body biplanar radiographs. Chin brow vertical angle (CBVA) and postural and
      cervical parameters were measured. Subjects were grouped according to cervical
      spine curvature (C2-C7 angle): kyphotic (< - 5 degrees ), straight [- 5 degrees ,
      5 degrees ], lordotic (> 5 degrees ). Demographics, SF-36 component scores and
      CBVA were compared between groups. All other parameters were compared between
      groups, while controlling for confounding factors (ANCOVA). A correlation test
      was conducted between all cervical parameters. RESULTS: 32% of subjects had
      kyphotic (- 12 degrees  +/- 7 degrees ), 27% straight (0 degrees  +/- 3 degrees )
      and 41% lordotic (12 degrees  +/- 7 degrees ) cervical spines. While demographic
      and SF-36 data did not differ between groups, CBVA differed between lordotic and
      kyphotic groups (2 degrees  vs. 6.5 degrees , p = 0.002). Sagittal vertical axis
      (SVA) and thoracic kyphosis (TK) were lower in the kyphotic group (SVA: K = - 26
      +/- 20 mm vs. L = - 2 +/- 21 mm, p < 0.001; TK: K = 40 degrees  +/- 6 degrees 
      vs. L = 51 degrees  +/- 8 degrees , p < 0.001). C2 slope (K = 29 degrees  +/- 6
      degrees  vs. L = 18 degrees  +/- 6 degrees , p < 0.001), C0-C2 (K = 42 degrees 
      +/- 8 degrees  vs. L = 30 degrees  +/- 8 degrees , p < 0.001) and C1-C2 (K = 33
      degrees  +/- 6 degrees  vs. L = 28 degrees  +/- 6 degrees , p = 0.004) were
      higher in the kyphotic group. Significant correlations were found between almost
      all cervical parameters and C2-C7 angle. CONCLUSIONS: Subjects with cervical
      kyphosis presented with more posterior global alignment and lower TK than
      subjects with lordosis. In order to maintain horizontal gaze, subjects with
      cervical kyphosis presented with a more lordotic upper cervical spine than
      subjects with cervical lordosis. Subjects with straight cervical curvature
      presented with an intermediate sagittal alignment. These slides can be retrieved
      under Electronic Supplementary Material.

PMID- 30194530
TI  - Motion analysis of dynamic cervical implant stabilization versus anterior
      discectomy and fusion: a retrospective analysis of 70 cases.
AB  - PURPOSE: Retrospective kinematic analysis of treated level, adjacent levels, and
      overall cervical spine after single-level dynamic cervical implant (DCI)
      stabilization versus anterior cervical discectomy and fusion (ACDF). METHODS:
      Between June 2009 and March 2013, 70 consecutive patients with a symptomatic
      single-level cervical degenerative disk disease (DDD) were enrolled in this study
      and divided into DCI (n = 35) group and ACDF (n = 35) group. All cases were
      followed up for more than 5 years. The study compared perioperative parameters;
      clinical outcomes; and radiological parameters. Kinematic analysis included range
      of motion (ROM) of treated level and adjacent level, overall ROM (C2-C7), and
      changes in adjacent disk spaces. RESULTS: There were no significant differences
      between the DCI group and ACDF group in terms of improvement in the SF-36, VAS,
      NDI, and JOA scores. DCI stabilization resulted in better ROM of C2-C7 and the
      treated level than ACDF did. The ROM of treated level decreased significantly at
      24 months after surgery and last follow-up in the DCI group, and the C2-C7 ROM
      showed different degrees of reduction after the 24 months after surgery.
      Radiological evidence of adjacent segment degeneration (ASD) at last follow-up
      was observed in 4/22 patients (18.2%) in the DCI group and 5/23 patients (21.7%)
      in the ACDF group which was not a significant difference between groups (p >
      0.05). CONCLUSIONS: DCI stabilization for the treatment of cervical DDD cannot
      preserve the normal kinematics of the cervical spine for a long time, especially
      the treated level. DCI stabilization cannot decrease the risk of ASD compared
      with ACDF. These slides can be retrieved under Electronic Supplementary Material.

PMID- 30194531
TI  - Multilevel spinal reconstruction in pediatric patients under 4 years old with non
      congenital pathology (10-year single-center cohort study).
AB  - PURPOSE: To evaluate the influence of anterior fusion option on the short- and
      long-time outcomes on multilevel spinal reconstructions in young children.
      METHODS: Forty-five patients aged under 4 years old (2 years 2 months +/- 11
      months in average) underwent spinal reconstruction due to tuberculosis
      spondylitis (35), pyogenic spondylitis (9) and spinal tumors (1) complicated by
      angular kyphosis exceeded 20 degrees  (49.2 degrees  +/- 14.3 degrees  in
      average). All lesions involved two or more spinal motion segments. Clinical and
      radiographic data were compared in two groups depended on the types of anterior
      fusion: titanium mesh cage with bone graft (TMC + BG) (19 patients) and cortical
      BG only (26). The average follow-up was 5 years 10 months +/- 2 years 8 months
      (min = 3 years; max = 12 years). RESULTS: The deformity correction was similar in
      groups. The operation time and blood loss were less in TMC + BG group (p = 0.001)
      as a times for anterior bone block formation (p < 0.001) and posterior
      instrumentation removal (p = 0.003). Ten late post-op complications registered
      include disease's recurrence (1), pseudoarthrosis (6), deformity progression (1)
      and graft resorption (1). The complication rate was less in TMC + BG than in BG
      group: two and eight cases consequently, p = 0.024. CONCLUSIONS: Multilevel
      spinal reconstruction in early aged patients is safe and effective procedure. The
      anterior fusion by TMC with bone autograft has advantages of reducing blood loss,
      operation time, time for anterior block formation and complications rate compared
      with bone autograft only. These slides can be retrieved under Electronic
      Supplementary Material.

PMID- 30194532
TI  - Percutaneous ultrasonographic evaluation of the spinal cord after cervical
      laminoplasty: time-dependent changes.
AB  - PURPOSE: The first purpose of this study is to confirm whether the spinal cord
      and the surrounding tissues can be visualized clearly after laminoplasty using
      percutaneous ultrasonography. And second purpose is to evaluate the changes in
      the status of the spinal cord over time. METHODS: Fifty patients who underwent
      cervical laminoplasty with suture anchors were evaluated using intraoperative
      ultrasonography and postoperative (1 week, 2 weeks, 3 months, 6 months, and 1
      year) percutaneous ultrasonography. We classified the decompression status of the
      spinal cord into three grades and the pattern of the spinal cord pulsation into
      six categories. Clinical outcomes were evaluated using the Japanese Orthopaedic
      Association Score for cervical myelopathy, and the recovery rate was calculated.
      RESULTS: In all cases and all periods, we could observe the status of the spinal
      cord using percutaneous ultrasonography after cervical laminoplasty. The
      decompression status of the spinal cord improved until 3 months postoperatively,
      and the clinical outcomes improved up to 6 months postoperatively. Although the
      pulsation pattern of the spinal cord varied in each individual and in each
      period, spinal pulsation itself was observed in all cases and all periods, except
      one, when an epidural hematoma caused quadriplegia and a revision surgery was
      needed. Decompression status and pulsation pattern of the spinal cord were not
      associated with clinical outcomes as far as pulsation was observed. CONCLUSIONS:
      Percutaneous ultrasonography was very useful method to evaluate the postoperative
      status of the spinal cord, particularly in the diagnosis of the postoperative
      epidural hematoma. These slides can be retrieved under Electronic Supplementary
      Material.

PMID- 30194533
TI  - Effects of a Multi-Component Workplace Intervention Program with Environmental
      Changes on Physical Activity among Japanese White-Collar Employees: a Cluster
      Randomized Controlled Trial.
AB  - PURPOSE: This study aimed to investigate effects of a flexible multi-component
      workplace intervention program for improving physical activity among Japanese
      white-collar employees in a cluster randomized controlled trial design. METHODS:
      A total of 208 worksites and nested employees were approached. Any worksite
      interested in a 3-month physical activity promotion intervention and white-collar
      workers aged 18 years or older were eligible. The worksites were randomly
      assigned to an intervention or a control, stratified by worksite size. The
      intervention worksites were offered an intervention program that allows these
      worksites to select intervention components from a set of options, including
      environmental changes. The control worksites were offered feedback and basic
      occupational health services. Physical activity level was measured using a self
      reported questionnaire at baseline and at 3 and 6 months of follow-up. RESULTS:
      Three worksites (92 employees) were allocated to the intervention and five
      worksites (98 employees) to the control worksites. The overall physical activity
      level in the intervention worksites significantly increased compared with the
      control worksites (Coeff = 0.45, SE = 0.19, p = 0.018). For subgroup analyses,
      the intervention effect on the overall physical activity level was significant
      among medium- and large-sized worksites but not among small-sized worksites.
      CONCLUSION: This trial showed a significant and positive effect of the
      intervention program on physical activity. The program is unique because of its
      flexibility and feasibility. However, small worksites might receive less benefit
      from the program, indicating a need for further support and/or new technologies.
      TRIAL REGISTRATION: UMIN Clinical Trials Registry (ID=UMIN000024069).

PMID- 30194534
TI  - Magnetic sensitivity mediated by the Arabidopsis blue-light receptor cryptochrome
      occurs during flavin reoxidation in the dark.
AB  - MAIN CONCLUSION: Arabidopsis cryptochrome mediates responses to magnetic fields
      that have been applied in the absence of light, consistent with flavin
      reoxidation as the primary detection mechanism. Cryptochromes are highly
      conserved blue-light-absorbing flavoproteins which have been linked to the
      perception of electromagnetic stimuli in numerous organisms. These include
      sensing the direction of the earth's magnetic field in migratory birds and the
      intensity of magnetic fields in insects and plants. When exposed to light,
      cryptochromes undergo flavin reduction/reoxidation redox cycles leading to
      biological activation which generate radical pairs thought to be the basis for
      magnetic sensitivity. However, the nature of the magnetically sensitive radical
      pairs and the steps at which they act during the cryptochrome redox cycle are
      currently a matter of debate. Here, we investigate the response of Arabidopsis
      cryptochrome-1 in vivo to a static magnetic field of 500 MUT (10 * earth's field)
      using both plant growth and light-dependent phosphorylation as an assay.
      Cryptochrome responses to light were enhanced by the magnetic field, as indicated
      by increased inhibition of hypocotyl elongation and increased cryptochrome
      phosphorylation. However, when light and dark intervals were given
      intermittently, a plant response to the magnetic field was observed even when the
      magnetic field was given exclusively during the dark intervals between light
      exposures. This indicates that the magnetically sensitive reaction step in the
      cryptochrome photocycle must occur during flavin reoxidation, and likely involves
      the formation of reactive oxygen species.

PMID- 30194535
TI  - Genetic control of fatty acid composition in coconut (Cocos nucifera), African
      oil palm (Elaeis guineensis), and date palm (Phoenix dactylifera).
AB  - MAIN CONCLUSION: Predominant gene isoforms and expression bias in lipid
      metabolism pathways are highly conserved between oil-producing Arecaceae crop
      species coconut and oil palm, but diverge in non-oil-producing species date palm.
      Coconut (Cocos nucifera), African oil palm (Elaeis guineensis) and date palm
      (Phoenix dactylifera) are three major crop species in the Arecaceae family for
      which genome sequences have recently become available. Coconut and African oil
      palm both store oil in their endosperms, while date palm fruits contain very
      little oil. We analyzed fatty acid composition in three coconut tissues (leaf,
      endosperm and embryo) and in two African oil palm tissues (leaf and mesocarp),
      and identified 806, 840 and 848 lipid-related genes in 22 lipid metabolism
      pathways from the coconut, African oil palm and date palm genomes, respectively.
      The majority of lipid-related genes were highly homologous and retained in
      homologous segments between the three species. Genes involved in the conversion
      of pyruvate to fatty acid had a five-to-sixfold higher expression in the coconut
      endosperm and oil palm mesocarp than in the leaf or embryo tissues based on
      Fragments Per Kilobase of transcript per Million mapped reads values. A close
      evolutionary relationship between predominant gene isoforms and high conservation
      of gene expression bias in the lipid and carbohydrate gene metabolism pathways
      was observed for the two oil-producing species coconut and oil palm, differing
      from that of date palm, a non-oil-producing species. Our results elucidate the
      similarities and differences in lipid metabolism between the three major
      Arecaceae crop species, providing important information for physiology studies as
      well as breeding for fatty acid composition and oil content in these crops.

PMID- 30194536
TI  - New heteroleptic oxidovanadium(V) complexes: synthesis, characterization and
      biological evaluation as potential agents against Trypanosoma cruzi.
AB  - Searching for prospective vanadium-based agents against Trypanosoma cruzi, the
      parasite causing Chagas disease, four new [VVO(8HQ-H)(L-2H)] compounds, where 8HQ
      is 8-hydroxyquinoline and L are tridentate salicylaldehyde semicarbazone
      derivatives L1-L4, were synthesized and characterized in the solid state and in
      solution. The compounds were evaluated on T. cruzi epimastigotes (CL Brener) as
      well as on VERO cells, as mammalian cell model. Compounds showed activity against
      T. cruzi (IC50 6.2-10.5 MUM) of the same order than Nifurtimox and 8HQ, and a
      four- to sevenfold activity increase with respect to the free semicarbazones. For
      comparison, [VVO2(L-H)] series was prepared and the new [VVO2(L3-H)] was fully
      characterized. They showed negligible activity and low selectivity towards the
      parasite. The inclusion of 8HQ as ligand in [VVO(8HQ-H)(L-2H)] compounds led to
      good activities and increased selectivity towards the parasite with respect to
      8HQ. 51V NMR experiments, performed to get insight into the nature of the active
      species, suggested partial decomposition of the compounds in solution to [VVO2(L
      H)] and 8HQ. Depending on the dose, the compounds act as trypanocide or
      trypanostatic. A high uptake of vanadium in the parasites (58.51-88.9% depending
      on dose) and a preferential accumulation in the soluble protein fraction of the
      parasite was determined. Treated parasites do not seem to show a late
      apoptotic/necrotic phenotype suggesting a different cell death mechanism. In vivo
      toxicity study on zebrafish model showed no toxicity up to a 25 uM concentration
      of [VVO(8HQ-H)(L1-2H)]. These compounds could be considered prospective anti-T.
      cruzi agents that deserve further research.

PMID- 30194538
TI  - Spatial Genomic Analysis: A Multiplexed Transcriptional Profiling Method that
      Reveals Subpopulations of Cells Within Intact Tissues.
AB  - Here, we present Spatial Genomic Analysis (SGA), a quantitative single-cell
      transcriptional profiling method that takes advantage of single-molecule imaging
      of individual transcripts for up to a hundred genes. SGA relies on a machine
      learning-based image analysis pipeline that performs cell segmentation and
      transcript counting in a robust way. SGA is suitable for various in situ
      applications and was originally developed to address heterogeneity in the neural
      crest, which is a transient embryonic stem cell population important for
      formation of various vertebrate body structures. After being specified as
      multipotent neural crest stem cells in the dorsal neural tube, they go through an
      epithelial to mesenchymal transition in order to migrate to different
      destinations around the body, and gradually turn from stem cells to progenitors
      prior to final commitment. The molecular details of this process remain largely
      unknown, and upon their emergence, the neural crest cells have been considered as
      a single homogeneous population. Technical limitations have restricted the
      possibility to parse the neural crest cell pool into subgroups according to
      multiplex gene expression properties. By using SGA, we were able to identify
      subgroups inside the neural crest niche in the dorsal neural tube. The high
      sensitivity of the method allows detection of low expression levels and we were
      able to determine factors not previously shown to be present in neural crest stem
      cells, such as pluripotency or lineage markers. Finally, SGA analysis also
      provides prediction of gene relationships within individual cells, and thus has
      broad utility for powerful transcriptome analyses in original biological
      contexts.

PMID- 30194537
TI  - The Asp99-Arg188 salt bridge of the Pseudomonas aeruginosa HemO is critical in
      allowing conformational flexibility during catalysis.
AB  - The P. aeruginosa iron-regulated heme oxygenase (HemO) is required within the
      host for the utilization of heme as an iron source. As iron is essential for
      survival and virulence, HemO represents a novel antimicrobial target. We recently
      characterized small molecule inhibitors that bind to an allosteric site distant
      from the heme pocket, and further proposed binding at this site disrupts a nearby
      salt bridge between D99 and R188. Herein, through a combination of site-directed
      mutagenesis and hydrogen-deuterium exchange mass spectrometry (HDX-MS), we
      determined that the disruption of the D99-R188 salt bridge leads to significant
      decrease in conformational flexibility within the distal and proximal helices
      that form the heme-binding site. The RR spectra of the resting state Fe(III) and
      reduced Fe(II)-deoxy heme-HemO D99A, R188A and D99/R188A complexes are virtually
      identical to those of wild-type HemO, indicating no significant change in the
      heme environment. Furthermore, mutation of D99 or R188 leads to a modest decrease
      in the stability of the Fe(II)-O2 heme complex. Despite this slight difference in
      Fe(II)-O2 stability, we observe complete loss of enzymatic activity. We conclude
      the loss of activity is a result of decreased conformational flexibility in
      helices previously shown to be critical in accommodating variation in the distal
      ligand and the resulting chemical intermediates generated during catalysis.
      Furthermore, this newly identified allosteric binding site on HemO represents a
      novel alternative drug-design strategy to that of competitive inhibition at the
      active site or via direct coordination of ligands to the heme iron.

PMID- 30194539
TI  - Associations between hyperacusis and psychosocial work factors in the general
      population.
AB  - PURPOSE: We investigated the association between hyperacusis and aspects of
      psychosocial work environment in a general population. The objectives were to
      investigate (1) prevalence and characteristics (among age, sex, access to social
      support at home, education, smoking, physical exercise, and perceived general
      health) of hyperacusis in a general working population and (2) associations
      between hyperacusis and psychosocial factors in the work environment. The
      psychosocial work aspects included effort, reward, overcommitment, worry, and
      social and emotional support. METHODS: Using data from a sample stratified for
      age and sex from the Osterbotten Environmental Health Study in Finland, currently
      employed participants with self-reported hyperacusis and referents were compared
      on questionnaire instruments quantifying six aspects of their psychosocial work
      environment. RESULTS: Among 856 currently employed participants, 47 constituted a
      hyperacusis group and 809 a reference group. The hyperacusis group scored
      significantly higher than the referents on worry at work, social support at work,
      and reward at work, but not on emotional support at work, work overcommitment, or
      effort at work. About 40% of the hyperacusis group scored on the upper quartile
      of the three former work environment factors, with odds ratios ranging from 1.91
      to 2.56. CONCLUSIONS: The results suggest that worrying about aspects at work,
      perceiving low social support, and not perceiving being rewarded at work are
      associated with hyperacusis.

PMID- 30194540
TI  - Electrostatic Gate Control in Molecular Transistors.
AB  - Molecular transistors, in which single molecules serve as active channel
      components in a three-terminal device geometry, constitute the building blocks of
      molecular scale electronic circuits. To demonstrate such devices, a gate
      electrode has been incorporated in several test beds of molecular electronics.
      The frontier orbitals' alignments of a molecular transistor can be delicately
      tuned by modifying the molecular orbital energy with the gate electrode. In this
      review, we described electrostatic gate control of solid-state molecular
      transistors. In particular, we focus on recent experimental accomplishments in
      fabrication and characterization of molecular transistors.

PMID- 30194542
TI  - Responding to New Psychoactive Substances in the European Union: Early Warning,
      Risk Assessment, and Control Measures.
AB  - New psychoactive substances (NPS) are drugs that are not controlled by the United
      Nations international drug control conventions of 1961 and 1971 but that may pose
      similar threats to public health. Many of them are traded as "legal" replacements
      to controlled drugs such as cannabis, heroin, benzodiazepines, cocaine,
      amphetamines, and 3,4-methylenedioxymethamphetamine (MDMA). Driven by
      globalization, there has been a large increase in the availability and,
      subsequently, harms caused by these substances over the last decade in Europe.
      The European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) is
      monitoring more than 670 NPS that have appeared on Europe's drug market in the
      last 20 years, of which almost 90% have appeared in the last decade. While some
      recent policy responses have been successful in reducing availability and sales
      of these substances in some settings - such as "legal highs" and "research
      chemicals" sold openly in the high street and online - and there are signs that
      growth in the market is slowing, new challenges have emerged. This includes
      monitoring a growing number of highly potent substances - including 179 synthetic
      cannabinoid receptor agonists and 28 fentanils - that can pose a high risk of
      life-threatening poisoning to users and can cause explosive outbreaks. This
      chapter briefly traces the origins of NPS, provides an overview of the situation
      in Europe, and discusses the work of the EMCDDA as part of a legal framework of
      early warning, risk assessment, and control measures that allows the European
      Union to rapidly detect, assess, and respond to public health and social threats
      caused by these substances.

PMID- 30194543
TI  - Therapeutic Drug Monitoring of Antidepressants.
AB  - For a number of antidepressants in current clinical use, concentrations in serum
      or plasma are a more reliable index of target drug concentrations than is dosage.
      For such drugs, therapeutic drug monitoring (TDM) may be a useful clinical guide
      for the purpose of maximizing the likelihood of favorable therapeutic outcome
      while minimizing the probability of clinical ineffectiveness or adverse side
      effects. TDM is of greatest benefit when a therapeutic range of serum
      concentrations has been well established. Even if such a range is not
      definitively determined, TDM can be of help in situations in which patients are
      refractory to therapy despite adequate or high dosages, when adverse events
      supervene even with low doses, or when noncompliance with the intended dosage
      plan is suspected. Serum antidepressant concentrations from TDM should be
      interpreted in the full context of the patient's demographic characteristics and
      clinical status, along with an understanding of the pharmacokinetics of the
      medication being taken, the timing of the sample in relation to the dosage
      regimen, and the specific laboratory assay procedure. TDM measurements may be
      costly, and the potential benefits of the information need to be weighed against
      the cost to the patient or to the health care system.

PMID- 30194541
TI  - Metabolic Abnormalities in Diabetes and Kidney Disease: Role of Uremic Toxins.
AB  - PURPOSE OF REVIEW: Chronic kidney disease (CKD) is characterized by the
      accumulation of uremic retention solutes (URS) and is associated with
      perturbations of glucose homeostasis even in absence of diabetes. The underlying
      mechanisms of insulin resistance, beta cell failure, and increase risk of
      diabetes in CKD, however, remain unclear. Metabolomic studies reported that some
      metabolites are similar in CKD and diabetic kidney disease (DKD) and contribute
      to the progression to end-stage renal disease. We attempted to discuss the
      mechanisms involved in the disruption of carbohydrate metabolism in CKD by
      focusing on the specific role of URS. RECENT FINDINGS: Recent clinical data have
      demonstrated a defect of insulin secretion in CKD. Several studies highlighted
      the direct role of some URS (urea, trimethylamine N-oxide (TMAO), p-cresyl
      sulfate, 3-carboxylic acid 4-methyl-5-propyl-2-furan propionic (CMPF)) in glucose
      homeostasis abnormalities and diabetes incidence. Gut dysbiosis has been
      identified as a potential contributor to diabetes and to the production of URS.
      The complex interplay between the gut microbiota, kidney, pancreas beta cell, and
      peripheral insulin target tissues has brought out new hypotheses for the
      pathogenesis of CKD and DKD. The characterization of intestinal microbiota and
      its associated metabolites are likely to fill fundamental knowledge gaps leading
      to innovative research, clinical trials, and new treatments for CKD and DKD.

PMID- 30194544
TI  - Other Antidepressants.
AB  - This chapter addresses the following FDA-approved medications for the treatment
      of major depressive disorder available for use in the United States including
      bupropion, mirtazapine, trazodone, vortioxetine, and vilazodone. These
      medications do not belong to one of the previously featured classes of
      antidepressants discussed in the preceding chapters. Each medication featured in
      this chapter has a unique structure and properties that target diverse receptors
      in the central nervous system. These diverse targets are distinct from other
      classes of medications used to treat major depressive disorder. This chapter will
      provide an overview of each medication's indication for use, history of
      development, pharmacology, metabolism, dosing recommendations, onset of action,
      use in special populations, safety and tolerability, adverse effects, potential
      interactions with additional medications, and data regarding possible overdose
      with available treatments.Bupropion was initially developed for its combined
      effects on the norepinephrine and dopamine neurotransmitters. Currently,
      bupropion is the only antidepressant on the market in the United States with no
      appreciable activity on serotonin concentrations in the central nervous system.
      Bupropion is extensively metabolized in humans into three active metabolites
      including hydroxybupropion, threohydrobupropion, and erythrohydrobuproprion each
      with substantial antidepressant activity. The most serious side effect of
      bupropion is the development of seizures, so the dose must be gradually titrated
      to a maximum dose of 450 mg per day of the immediate-release formulation and 400
      mg per day of the sustained-release formulation. Additional adverse effects
      include agitation, dry mouth, insomnia, headaches, migraines, nausea, vomiting,
      constipation, and tremor. The onset of action of bupropion is 2 weeks with full
      efficacy attained at 4 weeks of treatment. Bupropion produced similar depression
      remission rates when compared to SSRIs with a median time to relapse of 44 weeks.
      Bupropion has additionally been approved for smoking cessation and may have a
      combined role in treating nicotine cravings and depression.Mirtazapine has a
      unique method of action by enhancing norepinephrine and serotonin
      neurotransmission by blocking the alpha-2 presynaptic adrenoceptors resulting in
      increased release of serotonin at the nerve terminals. Mirtazapine additionally
      binds to the 5-HT2, 5-HT3, and H1 receptors resulting in increased sedation,
      which is the most common side effect. Additional side effects include increased
      appetite and weight gain, dizziness, and transient elevations in cholesterol
      levels and liver function tests. Mirtazapine is unlike any other antidepressant
      in that it also has a hormonal effect that reduces cortisol levels within the
      body. Patients on mirtazapine showed significant improvement in symptoms of major
      depressive disorder within the first 1-2 weeks of treatment with long-term
      studies at 40 weeks showing continued improvements in response rates in addition
      to lower relapse rates. Mirtazapine has an antagonistic effect at the central
      presynaptic 5-HT2 receptors and alpha-2 adrenergic inhibitory autoreceptors and
      heteroreceptors resulting in increased norepinephrine release with an indirect
      release of serotonin due to increased noradrenergic input to the raphe nucleus.
      Mirtazapine has an effective dose range from 15 to 45 mg once daily with a long
      half-life preventing dose adjustments more often than every 1-2 weeks.Trazadone
      is a 5-HT2A and 5-HT2C receptor antagonist and selective serotonin reuptake
      inhibitor. While trazodone has only been FDA approved for use in the treatment of
      major depressive disorder, it has been used off label for numerous conditions
      including insomnia, anxiety, dementia, Alzheimer's disease, substance abuse,
      schizophrenia, bulimia, and fibromyalgia. The most common adverse reaction is
      drowsiness, followed by dizziness, dry mouth, and nervousness. In the United
      States, trazadone is the second most commonly prescribed agent used to treat
      insomnia. The hypnotic action of this medication at lower doses is attributed
      primarily to the antagonism of the 5-HT2A receptors, H1 receptors, and alpha-1
      adrenergic receptors. The most active metabolite is m-chlorophenylpiperazine
      produced by the CYP3A4 enzyme, which is a more profound inhibitor of serotonin
      reuptake as compared to the parent molecule of trazadone. The maximum outpatient
      dose should not exceed 400 mg per day in divided doses, but in hospitalized
      patients, the dose may be increased to a maximum dose of 600 mg daily in divided
      doses while the patient is being actively monitored for side effects. One third
      of inpatients and one half of outpatients had a significant therapeutic response
      to trazadone by the end of the first week with the remainder of patients
      responding in 2-4 weeks of therapy.Vortioxetine is a novel antidepressant
      classified by the World Health Organization as a N06AX antidepressant that was
      derived from studies targeting the combination of direct serotonin transporter
      inhibition and 5-HT1A receptor modulation leading to rapid desensitization of the
      somatodendritic 5-HT1A autoreceptors and activation of the postsynaptic 5-HT1A
      receptors. This medication is an antagonist at 5-HT3, 5-HT1D, and 5-HT7
      receptors, an agonist at 5-HT1A receptors, and a partial agonist at 5-HT1B
      receptors. Blockade of the 5-HT3 receptor was noted to produce increased levels
      of serotonin, dopamine, norepinephrine, acetylcholine, and histamine in the
      prefrontal cortex and hippocampus, which are known to be associated with the
      development of depression. The most common adverse effect is nausea followed by
      sexual dysfunction, constipation, and vomiting. The maximum dose of vortioxetine
      is 20 mg daily with improvement in symptoms of depression noted at 2 weeks with a
      full therapeutic effect observed at 4-6 weeks.Vilazodone is a selective serotonin
      reuptake inhibitor and 5-HT1A receptor partial agonist. This medication works by
      enhancing serotonergic activity in the central nervous system through selective
      inhibition of serotonin reuptake with no significant effects noted on
      norepinephrine or dopamine uptake. Vilazodone additionally binds with high
      affinity to the 5-HT1A receptors as a partial agonist resulting in faster onset
      of action, greater efficacy, and better tolerability with reduced sexual side
      effects when compared to other SSRIs. The most common adverse effects were
      diarrhea, nausea, vomiting, and insomnia. Additional reported adverse effects
      included dizziness, dry mouth, fatigue, abnormal dreams, decreased libido,
      arthralgias, and palpitations which were self-limited with resolution in 4-5 days
      after starting the medication. The recommended therapeutic dose of vilazodone is
      40 mg daily with improvement noted in depressive symptoms within 1 week of
      initiating therapy with increased remission rates noted at 6 weeks of therapy.The
      medications featured in this chapter do not fall within the major categories of
      antidepressant classes but add additional unique mechanisms for the treatment of
      major depressive disorder. Each medication targets different receptors in the
      central nervous system involved in the development of depression. Resolution of
      depressive symptoms and response rates of these medications are similar to SSRIs
      with reduced side effects that can often lead to discontinuation of therapy. Use
      of these unique medications allows clinicians to target specific symptoms and
      comorbidities often associated with depression resulting in improved symptom
      resolution and long-term maintenance of remission.

PMID- 30194545
TI  - Modulation of Sympathetic Overactivity to Treat Resistant Hypertension.
AB  - PURPOSE OF REVIEW: To review the role and evidence for sympathetic overactivity
      in resistant hypertension and review the therapies that have been studied to
      modulate the sympathetic nervous system to treat resistant hypertension, with a
      focus on non-pharmacologic therapies such as renal denervation, baroreflex
      activation therapy, and carotid body ablation. RECENT FINDINGS: Based on the two
      best current techniques available for assessing sympathetic nerve activity,
      resistant hypertension is characterized by increased sympathetic nerve activity.
      Several device therapies, including renal denervation baroreflex activation
      therapy and carotid body ablation, have been developed as non-pharmacologic means
      of reducing blood pressure in resistant hypertension. With respect to renal
      denervation, the technologies for renal denervation have evolved since the
      unfavorable results from the HTN-3 study, and the revised technologies are being
      actively studied. Data from the first phase of the SPYRAL HTN Clinical Trial
      Program have been published. Results from the SPYRAL HTN-OFF MED trial suggest
      that ablating renal nerves can reduce blood pressure in patients with untreated
      mild-to-moderate hypertension. The SPYRAL HTN-ON MED trial demonstrated the
      safety and efficacy of catheter-based renal denervation in patients with
      uncontrolled hypertension on antihypertensive treatment. Interestingly, there was
      a high rate of medication non-adherence among patients with hypertension in this
      study. One attractive alternative to radiofrequency ablation is the use of
      ultrasound for renal denervation. Proof of concept data for the Paradise
      endovascular ultrasound renal denervation system was recently published in the
      RADIANCE-HTN SOLO trial. The results of this trial indicate that, among patients
      with mild to moderate hypertension on no medications, renal denervation with the
      Paradise system results in a greater reduction in both SBP and DBP at 2months
      compared with a sham procedure. Overall reductions were similar in magnitude to
      those noted in the SPYRAL HTN-OFF MED study. With respect to carotid body
      ablation, there is an ongoing proof of concept study that is investigating the
      safety and feasibility of ultrasound-based endovascular carotid body ablation in
      30 subjects with treatment-resistant hypertension outside of the USA. The
      sympathetic nervous system is an important contributor to resistant hypertension.
      Modulation of sympathetic overactivity should be an important goal of treatment.
      Innovative therapies using non-pharmacologic means to suppress the sympathetic
      nervous system are actively being studied to treat resistant hypertension.

PMID- 30194546
TI  - Trauma and Aging.
AB  - PURPOSE OF REVIEW: The aim of this paper is to present a succinct summary of the
      major scientific findings on trauma, posttraumatic stress disorder (PTSD), and
      aging over the past few years. RECENT FINDINGS: There have been several reports
      from longitudinal investigations using representative samples of veterans
      regarding traumatic exposure and subsequent effects on health and functioning.
      There has also been further documentation of the significant association between
      PTSD and dementia as well as accelerated aging in late life. Several studies
      indicate that older adults with PTSD are at risk of not receiving timely and
      appropriate mental health treatment, indicating that targeted outreach could be
      helpful in increasing service use and improving care. The current knowledge base
      would benefit from more research on traumatized older adults from non
      industrialized countries, as well as those in North America from diverse
      backgrounds, including ethnic and racial minorities, women, and those with
      cognitive impairments. Studies limited to adults aged 65 and over as well as
      those addressing disparities in the availability of mental health-related
      services within this population are warranted.

PMID- 30194547
TI  - Macular vessels density in diabetic retinopathy: quantitative assessment using
      optical coherence tomography angiography.
AB  - PURPOSE: The aim of this study was to evaluate macular perfusion using OCTA
      automated software algorithms; vessel area density (VD) and non-flow tool to
      measure FAZ area in treatment-naive diabetic eyes with moderate or severe NPDR
      and having macular edema, and correlate these parameters with LogMAR (logarithm
      of the minimum angle of resolution) visual acuity. Diabetic eyes without macular
      edema were included, to detect and define differences within the parameters
      between diabetic eyes with and without macular edema. METHODS: Forty-five
      diabetic eyes with diabetic macular edema, forty diabetic eyes without macular
      edema, and forty eyes of healthy controls were examined using OCTA (RTVue-XR
      Avanti; Optovue, Inc, Fremont, CA). The macular vessel area density (VD) and
      foveal avascular zone (FAZ) area were assessed and statistically compared between
      the three groups and also correlated with the foveal thickness and visual acuity.
      Data were entered and analyzed by SPSS 19. Quantitative data were presented as
      mean and standard deviation, and qualitative data presented as frequency
      distribution; independent samples t test, Chi square test and Pearson correlation
      were done. RESULTS: Mean whole image VD was 44.4 +/- 3.6 in diabetic eyes with
      DME, 45.6 +/- 4.2 in diabetics without DME, and 49 +/- 3.9 in control eyes (P =
      0.001). Diabetic eyes with DME had significantly lower vessels density values at
      the level of the deep retinal plexus (in the parafoveal, superior hemi, inferior
      hemi, temporal, superior, and nasal areas), when compared with diabetic eyes
      without DME. In diabetic eyes with DME, significant fair negative correlation was
      found between whole image vessels density at the level of the superficial retinal
      plexus and LogMAR VA (r = - 0.313, P = 0.036). Also, a significant fair positive
      correlation was found between FAZ area (at both the superficial and deep retinal
      plexus) and LogMAR visual acuity, in diabetic eyes with DME, where eyes with
      larger FAZ area had worse vision (P = 0.005 and P = 0.016, respectively).
      Diabetic eyes with DME had significantly larger FAZ area at the level of the
      superficial capillary plexus (mean superficial FAZ +/- SD 0.55 +/- 0.25) than
      diabetic eyes without edema (mean superficial FAZ +/- SD 0.41 +/- 0.12) and
      control subjects (mean superficial FAZ +/- SD 0.35 +/- 0.09). CONCLUSION: Using
      OCTA machine with AngioAnalytics parameters (vessel area density and non-flow
      area) helped in objective quantification of macular perfusion and accurately
      measuring the FAZ area in diabetic eyes with macular edema. Both parameters were
      significantly correlated with visual function in treatment-naive diabetic eyes
      with edema. These OCTA biomarkers could be used to predict visual function in
      such eyes, to monitor response to treatment.

PMID- 30194548
TI  - Regular physical activity and mammographic density: a cohort study.
AB  - PURPOSE: Physical activity is a modifiable lifestyle risk factor in prevention of
      breast cancer. Mammographic density (MD) is a strong risk factor for breast
      cancer. We investigate the association of regular physical activity with MD.
      METHODS: For 5,703 women who participated in the Danish Diet, Cancer and Health
      cohort (1993-1997) and attended mammographic screening in Copenhagen (1993-2001),
      MD was assessed at the first screening after cohort entry. MD was defined as a
      binary measure equivalent to Breast Imaging Report and Data System (BI-RADS) to
      either mixed/dense or fatty. Participation and duration in physical activities
      (hours/week) and confounders were assessed by questionnaire at cohort baseline.
      Logistic regression was used to estimate associations [odds ratios (OR), 95%
      confidence intervals (CI)] between physical activities and MD. RESULTS: 56.3% of
      women had mixed/dense MD and 47.6% participated in sports. We found a significant
      positive association between participation in sports (OR 1.15; 95% CI 1.03-1.28)
      and do-it-yourself work (1.17; 1.05-1.31) and odds of having mixed/dense MD,
      which attenuated (1.08; 0.96-1.22 and 1.11; 0.98-1.25, respectively) in a fully
      adjusted model. No associations were found for time spent on physical activities
      or total metabolic equivalent of task scores with MD, in fully adjusted models.
      There was no effect modification of association between any physical activities
      and MD by obesity (BMI >= 30 kg/m2) and menopause status. CONCLUSIONS: Physical
      activity is not a determinant of MD.

PMID- 30194549
TI  - Differences in cancer survival by sex: a population-based study using cancer
      registry data.
AB  - PURPOSE: Few large-scale studies have investigated sex differences in cancer
      survival and little is known about their temporal and age-related patterns.
      METHODS: We used cancer registry data for first primary cancers diagnosed between
      1982 and 2015 in Victoria, Australia. Cases were followed until the end of 2015
      through linkage to death registries. Differences in survival were assessed for 25
      cancers using the Pohar-Perme estimator of net survival and the excess mortality
      rate ratio (EMRR) adjusting for age and year of diagnosis. RESULTS: Five-year net
      survival for all cancers combined was lower for men (47.1%; 95% CI 46.9-47.4)
      than women (52.0%; 95% CI 51.7-52.3); EMRR 1.13 (95% CI 1.12-1.14; p < 0.001). A
      survival disadvantage for men was observed for 11 cancers: head and neck,
      esophagus, colorectum, pancreas, lung, bone, melanoma, mesothelioma, kidney,
      thyroid, and non-Hodgkin lymphoma. In contrast, women had lower survival from
      cancers of the bladder, renal pelvis, and ureter. For the majority of cancers
      with survival differences, the EMRR decreased with increasing age at diagnosis;
      for colorectal, esophageal, and kidney cancer, the EMRR increased with time since
      diagnosis. CONCLUSION: Identifying the underlying reasons behind sex differences
      in cancer survival is necessary to address inequalities, which may improve
      outcomes for men and women.

PMID- 30194551
TI  - Novel Polymeric Valve for Transcatheter Aortic Valve Replacement Applications: In
      Vitro Hemodynamic Study.
AB  - Transcatheter aortic valve replacement (TAVR) is a minimally-invasive approach
      for treating severe aortic stenosis. All clinically-used TAVR valves to date
      utilize chemically-fixed xenograft as the leaflet material. Inherent limitation
      of the tissue (e.g., calcific degeneration) motivates the search for alternative
      leaflet material. Here we introduce a novel polymeric TAVR valve that was
      designed to address the limitations of tissue-valves. In this study, we
      experimentally evaluated the hemodynamic performance of the valve and compared
      its performance to clinically-used valves: a gold standard surgical tissue valve,
      and a TAVR valve. Our comparative testing protocols included: (i) baseline
      hydrodynamics (ISO:5840-3), (ii) complementary patient-specific hydrodynamics in
      a dedicated system, and (iii) thrombogenicity. The patient-specific testing
      system facilitated comparing TAVR valves performance under more realistic
      conditions. Baseline hydrodynamics results at CO 4-7 L/min showed superior
      effective orifice area (EOA) for the polymer valve, most-notably as compared to
      the reference TAVR valve. Regurgitation fraction was higher in the polymeric
      valve, but within the ISO minimum requirements. Thrombogenicity trends followed
      the EOA results with the polymeric valve being the least thrombogenic, and
      clinical TAVR being the most. Hemodynamic-wise, the results strongly indicate
      that our polymeric TAVR valve can outperform tissue valves.

PMID- 30194552
TI  - Global sagittal alignment in elderly patients with osteoporosis and its
      relationship with severity of vertebral fracture and quality of life.
AB  - : We compared global sagittal alignment and quality of life in osteoporotic
      patients with and without vertebral compression fracture (VCF) and determined its
      relationship with VCF severity. The findings revealed osteoporotic patients with
      VCF showed decreased quality of life and worse global sagittal alignment, which
      was significantly associated with VCF severity. INTRODUCTION: The aim of this
      study was to compare the global sagittal alignment and quality of life in elderly
      osteoporotic patients with and without vertebral compression fracture (VCF), and
      to investigate the relationship between global sagittal alignment and severity of
      VCF. METHODS: A consecutive series of 72 female patients with osteoporosis aged
      over 60 years and 31 age-matched females without osteoporosis were prospectively
      enrolled. The patients were divided into VCF and non-VCF group. Patient's
      clinical demography, nature of VCF, and bone mineral density (BMD) were also
      recorded. Spinal deformity index was used to evaluate severity of VCF. EOS(r)
      biplanar imaging system was then used to evaluate global sagittal parameters: T1
      pelvic angle (TPA) and global sagittal angle (GSA). In addition, quality of life
      was assessed with self-reported questionnaires: the Oswestry Disability Index
      (ODI) and Short-form 12 (SF-12). RESULTS: Osteoporotic patients and controls were
      found to be significantly different in terms of TPA, GSA, and BMD. And in
      patients with VCF, they were found to have significantly higher TPA and GSA. TPA
      and GSA were significantly correlated with SF-12 and ODI. The number of VCF and
      SDI significantly correlated with global sagittal alignment. Using regression
      analysis, parameters significantly associated with abnormal global alignment were
      the number of VCF (OR = 1.13) and SDI (OR = 1.84). CONCLUSION: Osteoporotic
      patients with VCF showed worse global sagittal alignment and decreased quality of
      life. The number and severity of VCF had a negative influence on global sagittal
      balance, which indicates that poorer sagittal global alignment may imply worse
      quality of life and more severe VCF.

PMID- 30194550
TI  - Sleep-Wake Disorders in Stroke-Increased Stroke Risk and Deteriorated Recovery?
      An Evaluation on the Necessity for Prevention and Treatment.
AB  - PURPOSE OF REVIEW: Sleep-wake disorders (SWD) are common not only in the general
      population but also in stroke patients, in whom SWD may be pre-existent or appear
      "de novo" as a consequence of brain damage. Despite increasing evidence of a
      negative impact of SWD on cardiocerebrovascular risk, cognitive functions, and
      quality of life, SWD are insufficiently considered in the prevention and
      management of patients with stroke. This narrative review aims at summarizing the
      current data on the bidirectional link between SWD and stroke. RECENT FINDINGS:
      Several studies have demonstrated that sleep-disordered breathing (SDB) is an
      independent risk factor for stroke and has a detrimental effect on stroke
      recovery. Short and long sleep duration and possibly other SWD (e.g., insomnia,
      circadian rhythm disorders) may also increase the risk of stroke and influence
      its outcome. Data on SDB treatment increasingly indicate a benefit on stroke risk
      and evolution while treatment of other SWD is still limited. A systematic search
      for SWD in stroke patients is justified due to their high frequency and their
      negative impact on stroke outcomes. Clinicians should actively consider available
      treatment options.

PMID- 30194553
TI  - Clinical effectiveness of multi-wavelength photobiomodulation therapy as an
      adjunct to extracorporeal shock wave therapy in the management of plantar
      fasciitis: a randomized controlled trial.
AB  - The goal of our study was to investigate the cumulative effect of combining
      medium-energy extracorporeal shock wave therapy (ESWT) and photobiomodulation
      therapy (PBMT), as well as to compare between their relative effectiveness in the
      management of plantar fasciitis (PF). One hundred twenty participants with
      chronic PF, more than 6 months with failure to respond to conservative treatment,
      were randomly assigned into four equal groups. Participants received either ESWT
      with PBMT, ESWT (once a week), PBMT (three times a week), or sham-PBMT (three
      times a week) for three consecutive weeks. A home exercise program was also
      included for all four groups. Outcome measures included pressure pain threshold
      (PPT), visual analogue scale (VAS), and functional foot index disability subscale
      (FFI-d) that were collected prior to the first treatment session and at the end
      of the 3-week treatment period, as well as at a follow-up session, 12 weeks after
      the final treatment session. There were statistically significant improvements in
      post-intervention and follow-up PPT, VAS, and FFI-d values in all treatment
      groups (P < 0.0001). As for the sham-PBMT, no significant difference was found
      between the pre-, post-intervention and follow-up values (P > 0.05). Bonferroni
      correction test revealed that there was a significant difference between all the
      four groups in PPT, VAS, and FFI-d values (P < 0.0001). All active treatment
      groups maintained the treatment effect at the 12-week follow-up. Both ESWT and
      PBMT were effective in increasing PPT values, decreasing pain and increasing
      functional ability. Additionally, application of PBMT after ESWT was shown to be
      superior over ESWT and PBMT alone, and ESWT was superior over PBMT in terms of
      reducing pain sensitivity and increasing function.Level of Evidence II.

PMID- 30194554
TI  - Quality Control of Radiation Delivery for Lower Gastrointestinal Cancers.
AB  - OPINION STATEMENT: Assessing the quality of health care delivered is a priority
      across medical specialties, but it is particularly critical for radiation
      oncology, a field with rapid introduction of new technologies and treatment
      paradigms. Deviation from acceptable standards can lead to delivery of inferior
      therapies and medical errors that can directly compromise patient clinical
      outcome, thus leading to disparities in quality of care. Professional oncologic
      specialty societies often take ownership of standardizing best practices by
      issuing evidence-based disease-specific consensus guidelines. They also inform
      quality indicators that are set as requirements for accreditation, maintenance of
      certification, and reimbursement. Cooperative groups also create benchmarks for
      quality radiation therapy through design of clinical protocols that set standard
      of-care treatment practices. Pelvic radiotherapy for colorectal and anal cancers
      has undergone a significant transformation in radiation planning and delivery
      including increased complexity in contour segmentation with a transition from
      three-dimensional to intensity-modulated radiation therapy (IMRT). Compliance
      with quality metrics proposed in national consensus guidelines and participation
      in clinical trials help keep practicing radiation oncologists up-to-date with
      advances in our field and well-trained to provide safe and effective high-value
      care.

PMID- 30194555
TI  - A bilharzial pulmonary artery aneurysm with a large calcified mural thrombus.
AB  - Although very rarely encountered nowadays, bilharziasis should still be
      considered as one of the main causes of pulmonary artery aneurysms (PAA) and core
      pulmonale in endemic areas. The ideal treatment of PAA remains uncertain because
      there is no clear consensus about the best therapeutic approach, due to limited
      experience because of the rarity of the disease. Still the management of
      pulmonary artery thrombus is only through proper anticoagulation and follow-up
      with a very limited role for surgery.

PMID- 30194556
TI  - The effect of serum and follicular fluid secreted frizzle-related protein-5 on in
      vitro fertilization outcomes in patients with polycystic ovary syndrome.
AB  - In this study, we aimed to investigate serum and follicular fluid (FF) secreted
      frizzle-related protein-5 (Sfrp-5) levels in nonobese, nonhyperandrogenic
      patients with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization
      (IVF), in addition to IVF outcomes. In total, 160 patients undergoing IVF
      treatment were included in the study: 80 patients diagnosed with PCOS according
      to the Rotterdam criteria (group I, study) and 80 patients with the etiology of
      male factor infertility (group II, control). There were statistically significant
      between-group differences in serum estradiol (E2) levels on the day of hCG
      administration (2377.00 +/- 733.23 vs. 1931.3 +/- 1,010.69), the total
      gonadotropin dose required (2000.63 +/- 1,051.87 vs. 1.134.69 +/- 286.45), and
      the total number of retrieved oocytes (8.60 +/- 2.06 vs. 11.05 +/- 4.39) (p <
      0.05). There was also a statistically significant between-group difference in
      serum and FF Sfrp-5 levels on the day of oocyte retrieval (11.40 +/- 2.88 vs.
      8.87 +/- 1.85, p < 0.001; 11.06 +/- 2.30 vs. 9.71 +/- 2.15, p = 0.008;
      respectively). However, there were no between-group differences in fertilization
      rates, clinical pregnancy rates, and live birth rates (p > 0.05). A correlation
      analysis showed that serum and FF Sfrp-5 levels were associated with insulin and
      inflammatory markers (p < 0.05). In a selected population of nonobese,
      nonhyperandrogenic PCOS patients, there was a significant difference in Sfrp-5
      levels of the PCOS group versus those of the control group. Further studies are
      needed to determine the effects of Sfrp-5 in women with PCOS.

PMID- 30194557
TI  - Increased expression of microRNAs, miR-20a and miR-326 in PBMCs of patients with
      type 1 diabetes.
AB  - Type 1 diabetes (T1D) is an autoimmune disorder which is characterized by
      autoimmune attack on beta cells of pancreas and lack of insulin. The involvement
      of microRNAs (miRNAs) in the development of immune system and their differential
      expression in various autoimmune diseases including T1D have been well
      established. In this study, the association between expression levels of miR-20a,
      miR-326 and T1D were evaluated. The expression levels of miR-20a and miR-326 were
      measured in the PBMCs of 21 T1D patients and 16 healthy controls using qPCR
      method. In silico analysis was also performed on targetome of miR-20a and miR
      326. Both miR-20a (p value: 0.015) and miR-326 (p value: 0.005) were upregulated
      in the PBMCs of T1D patients compared to healthy controls. Furthermore, different
      dysregulated miR326-mRNA and miR20a-mRNA interactions were also suggested using
      integrative computational analysis. The expression level of miR-20a and miR-326
      indicates significant association with T1D which suggests the possible regulatory
      effects of these non-coding RNAs in T1D.

PMID- 30194559
TI  - Microbe-mediate transformation of echinocystic acid by whole cells of filamentous
      fungus Cunninghamella blakesleana CGMCC 3.910.
AB  - Structural modification of echinocystic acid (EA), a pentacyclic triterpenoid
      with wide spread biological activities was investigated by microbial
      transformation. Microbe-mediate transformation of EA was carried out by
      filamentous fungus Cunninghamella blakesleana CGMCC 3.910. Four metabolites
      3beta, 7beta, 16alpha-trihydroxy-olean-12-en-28-oic acid (EA-2); 3beta, 7beta,
      16beta,19beta-tetrahydroxy-olean-12-en-28-oic acid (EA-3); 3beta, 7beta, 16alpha,
      21beta-tetrahydroxy-olean-12-en-28-oic acid (EA-4); 3beta, 7beta, 16alpha
      trihydroxy-olean-11, 13(18)-dien-28-oic acid (EA-5) were produced. Structures of
      transformed products were elucidated by 1D and 2D NMR and HR-MS data. EA-3 and EA
      4 were new compounds.

PMID- 30194558
TI  - Molecular pathways involved in microRNA-mediated regulation of multidrug
      resistance.
AB  - Multidrug resistance (MDR) is still a major reason for therapeutic failure in
      cancers. The mechanisms underlying MDR are multifactorial and are not fully
      understood. miRNAs are evolutionarily conserved non-coding RNAs that function as
      key post-transcriptional regulators of gene expression. Emerging evidence
      indicates a vital role of miRNAs in the resistance to cancer treatments and
      suggests their potential for cancer therapy, as they can modulate multiple
      mechanisms link to the development of MDR. This review summarizes the recent
      findings on the role of miRNAs in MDR, and highlights the molecular targets and
      mechanisms of miRNA regulated pathways in MDR. Finally, the challenges and
      prospects of miRNA-targeted therapies for reversing drug resistance are reviewed.

PMID- 30194561
TI  - Isolation and characterization of Aquaporin 1 (AQP1), sodium/potassium
      transporting ATPase subunit alpha-1 (Na/K-ATPase alpha1), Heat Shock Protein 90
      (HSP90), Heat Shock Cognate 71 (HSC71), Osmotic Stress Transcription Factor 1
      (OSTF1) and Transcription Factor II B (TFIIB) genes from a euryhaline fish,
      Etroplus suratensis.
AB  - The present study reports the complete sequences of Aquaporin 1 (AQP1) gene and
      partial sequences of genes, Sodium/potassium-transporting ATPase subunit alpha-1
      (Na/K-ATPase alpha1 subunit), Osmotic Stress Transcription Factor 1 (OSTF1),
      Transcription Factor II B (TFIIB), Heat Shock Cognate 71 (HSC71) and Heat Shock
      Protein 90 (HSP90) obtained from mRNA and genomic DNA of Etroplus suratensis.
      They are candidate genes involved in stress responses of fishes. AQP1 gene was
      2163 bp long. Its mRNA sequence has 55 bp 5' UTR, 783 bp open reading frame
      (ORF), 119 bp 3' UTR, three intronic regions and 90% identity with AQP1 of
      Oreochromis niloticus. The partial Na/K-ATPase alpha1subunit gene obtained 5998
      bp length with an ORF of 2213 bp and 12 intronic regions. The partial OSTF1, TF
      IIB, HSC71 and HSP90 mRNA sequences obtained were 1473 bp, 587 bp, 1708 bp and
      151 bp in length respectively. All the genes showed a high sequence similarity
      with respective genes reported from fishes. Comparison of AQP1 and Na/K-ATPase
      alpha1 genomic DNA sequence of E. suratensis collected from different water
      system showed two type of AQP1 with one synonymous mutation in exon-1 and higher
      sequence difference in intronic regions (including addition, deletion, transition
      and transversion mutations) with few synonymous and non-synonymous mutations in
      the exons of Na/K-ATPase alpha1. The sequence information of these major
      candidate genes involved in stress responses will help in further studies on
      population genetics, adaptive variations and genetic improvement programs of this
      cichlid species having aquaculture, ornamental and evolutionary importance.

PMID- 30194560
TI  - Genetic characterization of Benin's wild populations of Sarotherodon melanotheron
      melanotheron Ruppell, 1852.
AB  - The Cichlid fish Sarotherodon melanotheron is typically found in West and Central
      African estuaries and lagoons. It represents a good candidate for promoting
      tilapia farming in brackish waters. Understanding the genetic diversity in its
      populations from the hydrographical basins of Southern Benin is primordial before
      designing selective breeding programs. For this purpose, 202 samples collected
      from four rivers of Southern Benin and were genotyped using 15 polymorphic
      microsatellite DNA markers. Each river was split up into three sampling sites. We
      found significant global linkage disequilibrium across the genome of natural
      populations of this tilapia species overall the loci. However, when the loci that
      display aberrant Wright's (FIS and FST) were removed from the data, a linkage
      disequilibrium was detected for the remaining 11 loci and became compatible with
      the null hypothesis. Null alleles explained at least 20.58% of FIS variation. We
      found a significant isolation by distance across subsamples. Effective population
      size averaged 210 individuals, with a range from 36 to 517 individuals. Assuming
      that 79% of heterozygote deficits are explained by sib mating lead to a rough
      estimate of rsm = 0.4 of mating rate between full sibs within S. melanotheron
      subpopulations. The fish size correlated positively and significantly with the
      observed FIS (r = 0.58; p value = 0.04806). Reproduction system (endogamy) in S.
      melanotheron could explain the strong heterozygote deficit observed. Our results
      provide technical guidance for efficient management of this tilapia species'
      genetic resources for breeding programs in fresh and brackish waters.

PMID- 30194562
TI  - Anticancer activity of Adiantum capillus veneris and Pteris quadriureta L. in
      human breast cancer cell lines.
AB  - Breast cancer is the most common cancer worldwide that costs lives of millions of
      people every year. Plant products with potential anticancer activities have
      become a vital source of novel agents in treating cancer. Adiantum capillus
      veneris (ACV) and Pteris Quadriureta (PQ) are such traditional herbs with
      potential pharmacological properties. In this study, both crude methanol extract
      and gold nanoparticles of ACV and PQ were tested for their anticancer activities
      in MCF7 and BT47 cell lines. By using GC-MS, we have identified 23 and 28
      bioactive compounds in ACV and PQ respectively. We analysed the effects of ACV
      and PQ nanoparticles on various proteins involved in cell cycle and apoptosis
      using western blotting and PCR. With the help of flow cytometry, we measured
      number of cells undergoing apoptosis. We found that both the crude extract and
      nanoparticles have anti-proliferative and apoptosis inducing properties against
      MCF7 and BT47 cell lines. We also performed molecular docking to check whether
      there were any interactions between proteins involved in apoptosis and cell cycle
      and bioactive compounds present in the plant extracts. By using docking analysis,
      we also showed that phytol and eicosapentaenoic acid present in ACV and PQ
      interact with Bcl2 and cyclin D1. These findings demonstrate that ACV and PQ
      possess anticancer activities by modulating proteins involved in cell cycle and
      apoptosis. ACV and PQ that effectively modulate various oncogenic molecules can
      be used as promising agent for cancer therapy.

PMID- 30194564
TI  - CDKI-73: an orally bioavailable and highly efficacious CDK9 inhibitor against
      acute myeloid leukemia.
AB  - Acute myeloid leukemia (AML) is the most common form of acute leukemia with
      dismal long-term prognosis with age. The most aggressive subtype of AML is MLL
      AML that is characterized by translocations of the mixed-lineage leukemia gene
      (MLL) and resistance to conventional chemotherapy. Cyclin dependent kinase 9
      (CDK9) plays a crucial role in the MLL-driven oncogenic transcription, and hence,
      inhibiting activity of CDK9 has been proposed as a promising strategy for
      treatment of AML. We investigated the therapeutic potential of CDKI-73, one of
      the most potent CDK9 inhibitors, against a panel of AML cell lines and samples
      derived from 97 patients. CDKI-73 induced cancer cells undergoing apoptosis
      through transcriptional downregulation of anti-apoptotic proteins Bcl-2, Mcl-1
      and XIAP by majorly targeting CDK9. Contrastively, it was relatively low toxic to
      the bone marrow cells of healthy donors. In MV4-11 xenograft mouse models, oral
      administration of CDKI-73 resulted in a marked inhibition of tumor growth (p <
      0.0001) and prolongation of animal life span (P < 0.001) without causing body
      weight loss and other overt toxicities. The study suggests that CDKI-73 can be
      developed as a highly efficacious and orally deliverable therapeutic agent for
      treatment of AML.

PMID- 30194563
TI  - Cannabis for the Treatment of Epilepsy: an Update.
AB  - PURPOSE OF REVIEW: For millennia, there has been interest in the use of cannabis
      for the treatment of epilepsy. However, it is only recently that appropriately
      powered controlled studies have been completed. In this review, we present an
      update on the research investigating the use of cannabidiol (CBD), a non
      psychoactive component of cannabis, in the treatment of epilepsy. RECENT
      FINDINGS: While the anticonvulsant mechanism of action of CBD has not been
      entirely elucidated, we discuss the most recent data available including its low
      affinity for the endocannabinoid receptors and possible indirect modulation of
      these receptors via blocking the breakdown of anandamide. Additional targets
      include activation of the transient receptor potential of vanilloid type-1
      (TRPV1), antagonist action at GPR55, targeting of abnormal sodium channels,
      blocking of T-type calcium channels, modulation of adenosine receptors,
      modulation of voltage-dependent anion selective channel protein (VDAC1), and
      modulation of tumor necrosis factor alpha release. We also discuss the most
      recent studies on various artisanal CBD products conducted in patients with
      epilepsy in the USA and internationally. While a high percentage of patients in
      these studies reported improvement in seizures, these studies were either
      retrospective or conducted via survey. Dosage/preparation of CBD was either
      unknown or not controlled in the majority of these studies. Finally, we present
      data from both open-label expanded access programs (EAPs) and randomized placebo
      controlled trials (RCTs) of a highly purified oral preparation of CBD, which was
      recently approved by the FDA in the treatment of epilepsy. In the EAPs, there was
      a significant improvement in seizure frequency seen in a large number of patients
      with various types of treatment-refractory epilepsy. The RCTs have shown
      significant seizure reduction compared to placebo in patients with Dravet
      syndrome and Lennox-Gastaut syndrome. Finally, we describe the available data on
      adverse effects and drug-drug interactions with highly purified CBD. While this
      product is overall well tolerated, the most common side effects are diarrhea and
      sedation, with sedation being much more common in patients taking concomitant
      clobazam. There was also an increased incidence of aspartate aminotransferase and
      alanine aminotransferase elevations while taking CBD, with many of the patients
      with these abnormalities also taking concomitant valproate. CBD has a clear
      interaction with clobazam, significantly increasing the levels of its active
      metabolite N-desmethylclobazam in several studies; this is felt to be due to
      CBD's inhibition of CYP2C19. EAP data demonstrate other possible interactions
      with rufinamide, zonisamide, topiramate, and eslicarbazepine. Additionally, there
      is one case report demonstrating need for warfarin dose adjustment with
      concomitant CBD. Understanding of CBD's efficacy and safety in the treatment of
      TRE has expanded significantly in the last few years. Future controlled studies
      of various ratios of CBD and THC are needed as there could be further therapeutic
      potential of these compounds for patients with epilepsy.

PMID- 30194565
TI  - FCN-based approach for the automatic segmentation of bone surfaces in ultrasound
      images.
AB  - PURPOSE: A new algorithm, based on fully convolutional networks (FCN), is
      proposed for the automatic localization of the bone interface in ultrasound (US)
      images. The aim of this paper is to compare and validate this method with (1) a
      manual segmentation and (2) a state-of-the-art method called confidence in phase
      symmetry (CPS). METHODS: The dataset used for this study was composed of 1738 US
      images collected from three volunteers and manually delineated by three experts.
      The inter- and intra-observer variabilities of this manual delineation were
      assessed. Images having annotations with an inter-observer variability higher
      than a confidence threshold were rejected, resulting in 1287 images. Both FCN
      based and CPS approaches were studied and compared to the average inter-observer
      segmentation according to six criteria: recall, precision, F1 score, accuracy,
      specificity and root-mean-square error (RMSE). RESULTS: The intra- and inter
      observer variabilities were inferior to 1 mm for 90% of manual annotations. The
      RMSE was 1.32 +/- 3.70  mm and 5.00 +/- 7.70 mm for, respectively, the FCN-based
      approach and the CPS algorithm. The mean recall, precision, F1 score, accuracy
      and specificity were, respectively, 62%, 64%, 57%, 80% and 83% for the FCN-based
      approach and 66%, 34%, 41%, 52% and 43% for the CPS algorithm. CONCLUSION: The
      FCN-based approach outperforms the CPS algorithm, and the obtained RMSE is
      similar to the manual segmentation uncertainty.

PMID- 30194566
TI  - Ferumoxytol Can Be Used for Quantitative Magnetic Particle Imaging of
      Transplanted Stem Cells.
AB  - PURPOSE: To evaluate, if clinically translatable ferumoxytol nanoparticles can be
      used for in vivo detection and quantification of stem cell transplants with
      magnetic particle imaging (MPI). PROCEDURES: Mesenchymal stem cells (MSCs) were
      labeled with ferumoxytol or ferucarbotran and underwent MPI, magnetic resonance
      imaging (MRI), Prussian blue staining, and inductively coupled plasma (ICP)
      spectrometry. Unlabeled, ferumoxytol, and ferucarbotran-labeled MSCs were
      implanted in calvarial defects of eight mice and underwent MPI, MRI, and
      histopathology. The iron concentration calculated according to the MPI signal
      intensity and T2 relaxation times of the three different groups were compared
      using an analysis of variance (ANOVA) with Bonferroni correction, and a p < 0.05.
      RESULTS: Compared to unlabeled controls, ferumoxytol- and ferucarbotran-labeled
      MSC showed significantly increased iron content, MPI signal and MRI signal. The
      ferumoxytol MPI signal was approximately 4* weaker compared to ferucarbotran at
      equimolar concentrations (p = 0.0003) and approximately 1.5* weaker for labeled
      cells when using optimized labeling protocols (p = 0.002). In vivo, the MPI
      signal of ferumoxytol-labeled MSC decreased significantly between day 1 and day
      14 (p = 0.0124). This was confirmed by histopathology where we observed a
      decrease in Prussian blue stain of MSCs at the transplant site. The MRI signal of
      the same transplants did not change significantly during this observation period
      (p = 0.93). CONCLUSION: Ferumoxytol nanoparticles can be used for in vivo
      detection of stem cell transplants with MPI and provide quantitative information
      not attainable with MRI.

PMID- 30194568
TI  - Safety and efficacy of intravenous ferric carboxymaltose in Japanese patients
      with iron-deficiency anemia caused by digestive diseases: an open-label, single
      arm study.
AB  - Iron-deficiency anemia (IDA) accounts for majority of anemia. Although iron
      replacement therapy is effective, in Japan, conventional iron formulations have
      disadvantages such as gastrointestinal side effects for oral formulations and
      issues of frequent administration for intravenous (IV) formulations. Ferric
      carboxymaltose (FCM), which overcomes these limitations, is widely used as an IV
      iron source overseas. In this multi-center, open-label, single-arm study, we
      investigated the safety and efficacy of FCM up to 12 weeks after the start of
      administration in patients with IDA caused by digestive diseases. Thirty-nine
      patients diagnosed with IDA based on hemoglobin and serum ferritin levels were
      included. Eligible subjects were administered FCM until the total calculated iron
      dose (1000 or 1500 mg) was achieved over intervals of at least 1 week. A single
      iron dose was 500 mg. In the full analysis set (n = 39), the incidence of adverse
      events and adverse drug reactions was 71.8 and 48.7%, respectively. All events
      were as expected from the safety profile of IV iron. The mean change from
      baseline (10.39 g/dL) to the highest observed hemoglobin level was 3.31 g/dL.
      These results indicate the safety and efficacy of FCM for treating IDA caused by
      digestive diseases in Japanese patients.

PMID- 30194567
TI  - A systematic review about costing methodology in robotic surgery: evidence for
      low quality in most of the studies.
AB  - OBJECTIVES: The main objective of this review was to evaluate the methodological
      design in studies reporting resource use and costs related to robotic surgery in
      gynecology. METHODS: Systematic searches were performed in the databases PubMed,
      Embase, Scopus, and The Centre for Reviews and Dissemination database for
      relevant studies before May 2016. The quality of the methodological design was
      assessed with items regarding methodology from the Consolidated Health Economic
      Evaluation Reporting Standards (CHEERS). The systematic review was reported
      according to the PRISMA guidelines. RESULTS: Thirty-two relevant studies were
      included. None of the reviewed studied fully complied with the CHEERS
      methodological checklist. Background and objectives, Target population and
      subgroups and Setting and location were covered in sufficient details in all
      studies whereas the Study perspective, Justification of the time horizon,
      Discount rate, and Estimating resources and costs were covered in less than 50%.
      Most of the studies (29/32) used the health care sector perspective whereas the
      societal perspective was applied in three studies. The time horizon was stated in
      18/32 of the studies. CONCLUSIONS: The methodological quality of studies
      evaluating costs of robotic surgery was low. The longest follow-up was 4 months
      and in general, the use of detailed cost data were lacking in most of the
      investigations. Key determinants, such as purchasing, maintenance costs of the
      robotic platform, and the use of surgical equipment, were rarely reported. If
      health care cost analyses lack transparency regarding cost drivers included it
      may not provide a true foundation for decision-making.

PMID- 30194569
TI  - Gender disparity in academic emergency radiology.
AB  - OBJECTIVE: This study is intended to better understand how academic productivity
      and career advancement differs between men and women emergency radiologists in
      academic practices. MATERIALS AND METHODS: Parameters of academic achievement
      were measured, including number of citations, number of publications, and h
      index, while also collecting information on academic and leadership ranking among
      emergency radiologists in North America. RESULTS: In emergency radiology, there
      are significantly fewer women than men (22.2% vs 77.8%). Of these women, the
      greatest proportion of women held the lower academic rank of assistant professor
      (95.4%). Female assistant professors had a higher h-index than men at the same
      rank (4 vs 2), but it was not statistically significantly higher. There was no
      significant difference between gender and academic (p = 0.089) or leadership (p =
      0.586) rankings. CONCLUSION: This study provides further evidence that gender
      disparity persists in emergency radiology, with women achieving less upward
      academic career mobility than men, despite better academic productivity in the
      earlier stages of their careers. The academic productivity of emergency
      radiologists at the rank of assistant professor is significantly higher for women
      than men.

PMID- 30194570
TI  - Synthesis of mesoporous core-shell TiO2 microstructures with coexposed
      {001}/{101} facets: enhanced intrinsic photocatalytic performance.
AB  - TiO2 microstructures were synthesized via a facile one-step route for enhanced
      intrinsic photocatalytic performance. The prepared TiO2 microstructures are
      featured by both mesoporous core-shell structures and coexposed {001}/{101}
      facets. Their intrinsic photocatalytic performance were remarkably enhanced due
      to their high specific surface area, coexposed {001}/{101} facets, and promoted
      separation of photogenerated carriers. Furthermore, the origin and detailed
      mechanism for diethylenetriamine (DETA) that served as a high efficient
      stabilizer of TiO2 {001} facet have been theoretically investigated. Finally, a
      new DETA-modified Ostwald ripening mechanism was originally proposed when
      studying the growth mechanism of the mesoporous core-shell TiO2 spherical
      microstructures with coexposed {001}/{101} facets.

PMID- 30194571
TI  - Correction to: Facile synthesis of carbon-coated layered double hydroxide and its
      comparative characterisation with Zn-Al LDH: application on crystal violet and
      malachite green dye adsorption-isotherm, kinetics and Box-Behnken design.
AB  - The original publication of this paper contains an error. The correct Figure 8 is
      shown in this paper.

PMID- 30194572
TI  - Lateral and longitudinal variation in phosphorus fractions in surface sediment
      and adjacent riparian soil in the Three Gorges Reservoir, China.
AB  - Hydrological regimes have been significantly altered since the Three Gorges Dam
      (TGD) raised the water level of the reservoir to the maximum design level of 175
      m in October 2010. This change might greatly influence the forms of phosphorus
      (P) in the sediment and the adjacent riparian soil. The purpose of this study was
      to reveal the lateral (sediment, water-level-fluctuation zone soil, and upland
      soil) and longitudinal (from the end of backwater area to the TGD) trends in P
      factions. Samples from 11 sites located along the main stem and ten sites located
      along eight tributaries were collected in June 2017. The P fractions were
      determined using the Standards, Measurements, and Testing (SMT) protocol. The
      results showed that the order of increase for average pH values was sediment
      (7.58 +/- 0.62), WLFZ soil (7.44 +/- 0.29), and adjacent upland soil (7.20 +/-
      0.68). The total organic carbon in the sediment was also highest with an average
      of 9.15 +/- 2.97 mg.g-1. The average concentrated HCl-extractable P (total P),
      organic P (OP), inorganic P (IP), HCl-extractable P (HCl-P), and NaOH-extractable
      P (NaOH-P) were 630.02 +/- 212.24, 161.89 +/- 90.77, 468.13 +/- 194.92, 335.65 +/
      159.88, and 51.40 +/- 36.20 mg.kg-1, respectively. The concentration of both
      total P and NaOH-P in the sediment of the main stem exhibited an increasing trend
      from the backwater area to the TGD. The average concentration of P species in the
      sediment was higher than those in the upland soil and the water-level-fluctuation
      zone (WLFZ) soil. For all the sediment and soil samples, the rank order of P
      species concentrations was HCl-P > OP > NaOH-P. Both IP and HCl-P were highly
      positively correlated with total P in the upland soil, the WLFZ soil and the
      sediment. However, only in the sediment, NaOH-P was positively correlated with
      total P and OP. All P species in the upland soil demonstrated greater spatial
      heterogeneity than those in the WLFZ soil and the sediment. Redundancy analysis
      revealed that the main variables explaining the variance in P species
      concentrations were Al in the upland soil and pH in the sediment.

PMID- 30194573
TI  - Effective phytoremediation of low-level heavy metals by native macrophytes in a
      vanadium mining area, China.
AB  - Heavy metal contamination, particularly vanadium contamination in mining and
      smelting areas, is a worldwide serious problem threatening the ecological system
      and human health. The contamination level of vanadium, arsenic, cadmium,
      chromium, mercury, and lead in sediments and waters in a vanadium mining area in
      China was investigated in the present study. The behavior of heavy metal uptake
      by 12 native aquatic macrophytes was evaluated, including 5 species of emergent
      aquatic plants (Acorus calamus, Scirpus tabernaemontani, Typha orientalis,
      Phragmites australis, and Bermuda grass), 3 species of floating plants (Marsilea
      quadrifolia, Nymphaea tetragona, and Eleocharis plantagineiformis), and 4 species
      of submerged plants (Hydrilla verticillata, Ceratophyllum demersum, Myriophyllum
      verticillatum, and Potamogetom crispus). Different heavy metal accumulation
      abilities were found across these macrophytes. Generally, they tended to
      accumulate higher contents of chromium, and C. demersum showed a particularly
      higher accumulation capacity for vanadium. The heavy metals were preferentially
      distributed in roots, instead of translocation into leaves and stems, indicating
      an internal detoxification mechanism for heavy metal tolerance in macrophytes. In
      24-day laboratory hydroponic experiments, the macrophytes had a satisfied
      phytoremediation performance for heavy metals, when their concentrations were at
      the microgram per liter level. Particularly, vanadium was effectively removed by
      P. australis and C. demersum, the removal efficiencies of which were
      approximately 50%. In addition, a combination of terrestrial plant (Bermuda
      grass) and aquatic macrophytes (P. australis, M. quadrifolia, and C. demersum)
      exhibited high uptake capacity of all the six heavy metals and their residual
      concentrations were 95 (vanadium), 39.5 (arsenic), 4.54 (cadmium), 17.2
      (chromium), 0.028 (mercury), and 7.9 (lead) MUg/L, respectively. This work is of
      significant importance for introducing native macrophytes to remove low-level
      heavy metal contamination, particularly vanadium, and suggests phytoremediation
      as a promising and cost-effective method for in situ remediation at mining sites.

PMID- 30194574
TI  - Effects of particulate matter (PM2.5) and associated acidity on ecosystem
      functioning: response of leaf litter breakdown.
AB  - Particulate matter (PM2.5 with the diameter <= 2.5 MUm) as one of the most
      harmful and complex pollutants can reduce environment quality and affect human
      health. Through acidification by wet deposition, PM2.5 can cause acid rain to
      impact aquatic ecosystems. However, our understanding of PM2.5 effect on
      ecosystem functioning is highly limited. This study investigated the relationship
      between PM2.5 concentration, associated acidity, and leaf litter breakdown of
      three tree species in laboratory experimental mesocosms, which are weeping willow
      (Salix babylonica), camphor tree(Cinnamomum camphora), and the south magnolia
      (Magnolia grandiflora). We found that leaf litter breakdown was significant
      affected by PM2.5 and associated acidity. With the increase of acidity, the leaf
      breakdown rate of all three tree species decreased. With the increase of PM2.5
      concentration, the leaf breakdown rates of those leaves slowed down. When
      considering the influence of leaf toughness, willow leaves with lower toughness
      had a higher breakdown rate than that of camphor tree and the south magnolia. Our
      study suggests that PM2.5 has significant impact on the aquatic ecosystem
      functioning through increasing acidification in aquatic environment. Hence, along
      with ecological restoration of local aquatic habitats, further freshwater
      ecosystem management should include reducing air pollution through regional
      efforts of best ecosystem management.

PMID- 30194575
TI  - Financial development, globalization, and CO2 emission in the presence of EKC:
      evidence from BRICS countries.
AB  - This study examines the impact of energy consumption, financial development,
      globalization, economic growth, and urbanization on carbon dioxide emissions in
      the presence of Environmental Kuznets Curve (EKC) model for BRICS economies, by
      using a family of econometric techniques robust to heterogeneity and cross
      sectional dependence. Results from LM test, CIPS and CADF unit root test,
      Westerlund Cointegration test, the Dynamic seemingly unrelated regression (DSUR),
      and Dumitrescu-Hurlin Granger causality test show that (i) the data is cross
      sectionally dependent and heterogeneous; (ii) carbon dioxide emissions, energy
      consumption, financial development, globalization, economic growth, square of GDP
      and urbanization have integration of order one; (iii) the examined variables are
      co-integrated; (iv) energy consumption and financial development contribute to
      the carbon dioxide emissions whereas globalization and urbanization have negative
      but insignificant relationship with carbon dioxide emissions; (v) supports the
      EKC hypothesis in BRICS economies; (vi) bidirectional causality exists among
      energy consumption, financial development, economic growth and square of GDP with
      carbon dioxide emissions whereas globalization and urbanization have
      unidirectional relationship with carbon dioxide emissions. Since these panel
      techniques account for heterogeneity and cross-sectional dependence in their
      estimation procedure, the empirical results are robust and reliable for policy
      recommendations. Furthermore, this study also uses time series tests (ADF, P-P,
      and FMOLS) to find the empirical results for each of the country and finds mixed
      results. Empirical findings directed towards some important policy implications.

PMID- 30194576
TI  - Biofilter with mixture of pine bark and expanded clay as packing material for
      methane treatment in lab-scale experiment and field-scale implementation.
AB  - Low methane (CH4) emission reduction efficiency (< 25%) has been prevalent due to
      inefficient biological exhaust gas treatment facilities in mechanic biological
      waste treatment plants (MBTs) in Germany. This study aimed to quantify the
      improved capacity of biofilters composed of a mixture of organic (pine bark) and
      inorganic (expanded clay) packing materials in reducing CH4 emissions in both a
      lab-scale experiment and field-scale implementation. CH4 removal performance was
      evaluated using lab-scale biofilter columns under varied inflow CH4
      concentrations (70, 130, and 200 g m-3) and corresponding loading rates of 8.2,
      4.76, and 3.81 g m-3 h-1, respectively. The laboratory CH4 removal rates (1.2-2.2
      g m-3 h-1) showed positive correlation with the inflow CH4 loading rates (4-8.2 g
      m-3 h-1), indicating high potential for field-scale implementation. Three field
      scale biofilter systems with the proposed mixture packing materials were
      constructed in an MBT in Neumunster, northern Germany. A relatively stable CH4
      removal efficiency of 38-50% was observed under varied inflow CH4 concentrations
      of 28-39 g m-3 (loading rates of 1120-2340 g m-3 h-1) over a 24-h period. The CH4
      removal rate was approximately 500-700 g m-3 h-1, which was significantly higher
      than relevant previously reported field-scale biofilter systems (16-50 g m-3 h
      1). The present study provides a promising configuration of biofilter systems
      composed of a mixture of organic (pine bark) and inorganic (expanded clay)
      packing materials to achieve high CH4 emission reduction. Graphic abstract ?.

PMID- 30194577
TI  - Microbial explanations for field-aged biochar mitigating greenhouse gas emissions
      during a rice-growing season.
AB  - Knowledge about the impacts of fresh and field-aged biochar amendments on
      greenhouse gas (CH4, N2O) emissions is limited. A field experiment was initiated
      in 2012 to study the effects of fresh and field-aged biochar additions on CH4 and
      N2O emissions and the associated microbial activity during the entire rice
      growing season in typical rice-wheat rotation system in Southeast China. CH4 and
      N2O fluxes were monitored, and the abundance of methanogen (mcrA), methanotrophy
      (pmoA), ammonia-oxidizing archaea (AOA), ammonia-oxidizing bacteria (AOB),
      nitrite reductase (nirS, nirK), N2O reductase (nosZ), and potential soil enzyme
      activities related to CH4 and N2O were simultaneously measured throughout
      different rice developmental stages. There were three treatments: control (urea
      without biochar), fresh BC (urea with fresh biochar added in 2015), and aged BC
      (urea with 3-year field-aged biochar added in 2012). Results showed that field
      aged biochar significantly decreased seasonal CH4 emissions by 16.8% in relation
      to the fresh biochar, though no significant differences were detected between
      biochars and control treatment. The structural equation model indicated that soil
      pH, microbial biomass carbon (MBC), pmoA, and mcrA were the main factors directly
      influenced by fresh and aged biochar amendments; aged biochar showed a negative
      effect while fresh biochar showed positive effects on CH4 fluxes. Both fresh and
      field-aged biochar obviously increased AOA and AOB abundances and reduced the
      (nirS+nirK)/nosZ ratio during the entire rice-growing season, although no
      significant effects were observed on seasonal N2O emissions. Therefore, biochar
      amendment produced long-term effects on total CH4 and N2O emissions through
      observed influences of soil pH and functional gene abundance. The figure shows
      how fresh and field-aged biochar differentially affected CH4 production and
      oxidation and N2O production and reduction through related functional gene
      abundances. Blue arrows indicate suppressing while pink arrows indicate promoting
      effect.

PMID- 30194578
TI  - Photodegradation of clothianidin and thiamethoxam in agricultural soils.
AB  - Presented in this paper is a study on the photodegradation of two widely used
      neonicotinoid insecticides clothianidin and thiamethoxam in three soils and in
      solid phase. The effects of light with differing wavelengths were examined using
      the natural sunlight and single ultraviolet A (UVA) and ultraviolet B (UVB) light
      sources. The results indicated that UVB played a key role in the photodegradation
      of clothianidin and thiamethoxam while the effects of visible and UVA lights were
      negligible. The degradations of clothianidin and thiamethoxam under all the light
      sources followed the first-order kinetics, and the half-lives of clothianidin and
      thiamethoxam in the three soils under the sunlight ranged from 97 to 112 h and 88
      to 103 h, respectively. When clothianidin and thiamethoxam were directly exposed
      to the sunlight without soil, the degradation rates were remarkably higher with
      half-lives being 13 and 10 h, respectively. Therefore, the insecticides fallen on
      the surface of soils would be degraded under sunlight much faster than those that
      enter the soils. The examination of the degradation products revealed four
      compounds from the photodegradation of clothianidin and three from thiamethoxam,
      and clothianidin was one of the photodegradation products of thiamethoxam.

PMID- 30194579
TI  - Spatio-temporal variability and source identification for metal contamination in
      the river sediment of Indian Sundarbans, a world heritage site.
AB  - Metal pollution is a subject of growing concern as it affects the whole food
      chain of an ecosystem by bioaccumulation. Growing industrialization and
      anthropogenic intervention have put tremendous pressure on self-sustaining
      ecosystems worldwide. Sundarbans mangrove estuary, being a UNESCO World Heritage
      site, suffers severely from anthropogenic stress, urbanization, ecotourism,
      overexploitation of natural resources and discharges of industrial as well as
      municipal waste products. Our study unfolds the extent of metal pollution in the
      sediment of this estuarine mangrove ecosystem and also investigates the source
      and distribution of these metals. Extensive samplings were performed during three
      major seasons, namely pre-monsoon, monsoon, and post-monsoon for two consecutive
      years at ten sampling stations along the major river networks of the mangrove
      estuary. Seasonal variations of these metals, physicochemical properties, and
      soil texture studies were performed to explore the sediment quality of the study
      area. Positive correlation was observed between the pollutants and siltation.
      Several environmental indices were investigated to explore the degree of metal
      pollution which revealed contamination of Cd, Cr, and Pb to cross the permitted
      safe index in the study area. Pollution load index indicates the spatial as well
      as seasonal variation of eco toxic metal load along the course of the rivers.
      Statistical analyses such as principal component analysis and correlation matrix
      identified different sources for metal contamination. Almost 700 tannery
      industries are located in the upstream region of the rivers, and several small-
      and large-scale battery industries seem to be the main possible source for Cd,
      Cr, and Pb pollution. Analysis of the results indicates the alarming condition of
      this heritage site. The metal concentrations beyond toxicity thresholds are
      responsible for gradual deterioration of this estuarine mangrove which may only
      be protected by developing sustainable management planning.

PMID- 30194580
TI  - The potential adsorption mechanism of the biochars with different modification
      processes to Cr(VI).
AB  - Modified biochar has attracted wide attention due to its advantageous adsorption
      performance. However, the influence of modification process of biochar on
      adsorption capacity was seldom studied. In this study, biochar derived from corn
      stalks was modified through two kinds of modification processes: pre-pyrolysis
      (MBCpre) and post-pyrolysis (MBCpost) modification with citric acid, sodium
      hydroxide, ferric chloride, respectively. The results showed that the biochar
      modified by ferric chloride (MBC) provided better adsorption capacity for Cr(VI),
      and the pre-pyrolysis offered more favorable adsorption capacity for biochar than
      post-pyrolysis. By means of instrumental analysis, it was found that MBCpre owned
      highly dispersed Fe3O4 particles and larger surface area, which could be the
      critical role for enhancing the adsorption capacity of MBCpre. Meanwhile, MBCpost
      appeared more protonated oxygen-rich functional groups(C=O, -OH, etc.) and
      adsorbed Cr(VI) by electrostatic attraction and complexation. This study will
      offer a novel idea for the treatment of chromium-containing wastewater by
      selecting the modification processes of biochar. Graphical abstract.

PMID- 30194581
TI  - Correlation of bone marrow cellularity and metabolic activity in healthy
      volunteers with simultaneous PET/MR imaging.
AB  - OBJECTIVE: To evaluate the correlation between bone marrow cellularity (BMC) and
      metabolic activity in healthy subjects and to see whether yellow marrow is indeed
      metabolically quiescent. Because metabolic activity can be assumed to reflect
      vascularity, we assessed the relationship between regional metabolic activity and
      geographic frequency of metastases as noted in the literature. MATERIALS AND
      METHODS: Two hundred and twenty locations (ten in each side of the pelvis and
      proximal femur) were evaluated in 11 consecutive healthy volunteers with
      simultaneous PET/MR. BMC was calculated through precise water-fat fraction
      quantification with a 6-echo gradient echo. We analyzed correlations between
      cellularity and SUVr, age, and R2*. We also looked at the relation between our
      results and the reported prevalence of metastases. RESULTS: There was moderate
      but statistically significant correlation between BMC and metabolic activity (r =
      0.636, p < 0.0001). Interestingly, the iliac and sacrum had higher metabolic
      activity relative to cellularity, whereas the femoral neck and lesser trochanter
      showed lower SUVr than other regions with the similar cellularity. The relatively
      lower metabolic status of the femoral neck conflicted with its reported high
      frequency of metastasis. Excluding regions with almost no remaining red marrow,
      cellularity showed inverse relationship with age (r = 0.476, p < 0.0001) and
      direct relationship with R2* (r = 0.532, p < 0.0010). CONCLUSIONS: Metabolic
      activity of bone marrow was largely dependent on BMC while yellow marrow seems
      metabolically quiescent. The discrepancy between the assumed vascularity as
      determined by metabolic activity and reported sites of metastasis suggested that
      the process of bone metastasis may not depend entirely on vascularity.

PMID- 30194582
TI  - Estradiol attenuates ischemia reperfusion-induced acute kidney injury through
      PPAR-gamma stimulated eNOS activation in rats.
AB  - We investigated the involvement of peroxisome proliferator activated receptor
      gamma (PPAR-gamma)/endothelial nitric oxide synthase (eNOS) pathway in estradiol
      mediated protection against ischemia reperfusion (I/R)-induced acute kidney
      injury (AKI) in rats. To induce AKI, rats underwent 40 min of bilateral renal
      ischemia followed by 24 h of reperfusion. I/R-induced kidney damage was
      quantified by measuring serum creatinine, creatinine clearance, urea nitrogen,
      uric acid, potassium, fractional excretion of sodium, microproteinuria, and renal
      oxidative stress (thiobarbituric acid reactive substances, superoxide anion
      generation, and reduced glutathione). Hematoxylin eosin stain demonstrated renal
      histology, while renal expression of apoptotic markers (Bcl-2, Bax), PPAR-gamma
      and eNOS were quantified by immunohistochemistry. Estradiol (1 mg/kg, i.p.) was
      administered 30 min before I/R in rats. In separate groups, PPAR-gamma
      antagonist, BADGE (30 mg/kg, i.p.), and NOS inhibitor, L-NAME (20 mg/kg, i.p.)
      were administered prior to estradiol treatment, which was followed by I/R in
      rats. I/R caused significant renal damage as demonstrated by biochemical
      (serum/urine), renal oxidative stress and histological changes alongwith
      increased expression of Bax and decreased levels of Bcl-2, PPAR-gamma and eNOS,
      which were prevented by estradiol. Pre-treatment with BADGE and L-NAME abolished
      estradiol mediated renoprotection. Notably, I/R + estradiol + BADGE group
      revealed decreased expression of PPAR-gamma and eNOS in renal tissues. In I/R +
      estradiol + L-NAME group, eNOS expression was reduced while PPAR-gamma levels
      remained unchanged. These results suggest that estradiol modulates PPAR-gamma
      which consequently regulates eNOS expression in rat kidneys. We conclude that
      estradiol protects against I/R-induced AKI through PPAR-gamma stimulated eNOS
      activation in rats.

PMID- 30194583
TI  - Hydrogen bond-linked pathways of peptide units and polar groups of amino acid
      residues suitable for electron transfer in cytochrome c proteins.
AB  - Electron transfer occurs through heme-Fe across the cytochrome c protein. The
      current models of long range electron transfer pathways in proteins include
      covalent sigma-bonds, van der Waals forces, and through space jump. Hydrogen-bond
      linked pathways of delocalized electron units in peptide units and polar side
      chains of amino acid residues in proteins and internal water molecules are better
      suited for intramolecular atom-to-atom electron transfer in proteins. Crystal
      structures of cytochrome c proteins from horse (1HRC), tuna (3CYT), rice (1CCR),
      and yeast (3CX5) were analyzed using pymol software for 'Hydrogen Bonds' marking
      the polar atoms within the distance of 2.6-3.3 A and tracing the atom-to-atom
      pathways linked by hydrogen bonds. Pathways of hydrogen-bond-linked peptide
      units, polar side chains of the amino acid residues, and buried water molecules
      connect heme-Fe through axially coordinated Met80-S and His18-N have been traced
      in cytochrome c proteins obtained from horse, tuna, rice and yeast with an
      identical hydrogen-bonded sequence around the heme-Fe: Asn-N-water-O-Tyr-O-Met-S
      heme-Fe-His (HN-C=N)-Pro-Asn-Pro-Gly (peptide unit, HN-C=O)-water-O. More than
      half of the amino acid residues in these pathways are among the conserved list
      and delocalized electron units, internal water molecules and hydrogen bonds are
      conspicuous by their presence.

PMID- 30194584
TI  - Cost-Effectiveness of Elbasvir/Grazoprevir Versus Daclatasvir Plus Asunaprevir in
      Patients with Chronic Hepatitis C Virus Genotype 1b Infection in China.
AB  - BACKGROUND AND OBJECTIVE: New direct-acting antivirals (DAAs) have high efficacy
      and tolerability in the treatment of hepatitis C virus (HCV) infection. The
      objective of this study was to assess the cost-effectiveness of
      elbasvir/grazoprevir (EBR/GZR) versus daclatasvir plus asunaprevir (DCV + ASV) in
      Chinese patients with chronic HCV genotype (GT) 1b infection stratified by
      cirrhosis status and treatment history. METHODS: A cohort state-transition model
      was constructed to simulate the course of chronic HCV infection in patients
      stratified by cirrhosis status and treatment history. The model projected
      lifetime outcomes and costs in terms of HCV treatment, laboratory tests, clinical
      procedures, and hospitalizations. Mean age of the study cohort at baseline was 45
      years, based on published sources. Sustained virologic response (SVR) rates were
      derived from clinical trials. Healthcare resource utilization and health
      utilities were extracted or estimated from published studies in Chinese
      populations. The stability of the base-case analysis was validated by
      deterministic and probabilistic sensitivity analyses. RESULTS: In each
      subpopulation of Chinese patients, treatment with EBR/GZR dominated treatment
      with DCV + ASV, with lower costs and higher quality-adjusted life-years (QALYs).
      Sensitivity analysis demonstrated that EBR/GZR was the cost-effective option
      compared to DCV + ASV in 77.4-97.4% or 94.1-100% of model simulations in Chinese
      treatment-naive or treatment-experienced patients, respectively, as the cost
      effectiveness threshold changed from zero to US$24,150/QALY (three times GDP per
      capita in China). CONCLUSIONS: Treatment with EBR/GZR was the cost-effective
      option for patients with chronic HCV GT1b infection in China, regardless of
      cirrhosis status or treatment history.

PMID- 30194585
TI  - Pharmacokinetics and Safety After a Single Dose of Imarikiren in Subjects with
      Renal or Hepatic Impairment.
AB  - BACKGROUND AND OBJECTIVE: Imarikiren hydrochloride (TAK-272; SCO-272) is a novel
      direct renin inhibitor. The objective of this study was to determine the effects
      of renal impairment (RI) or hepatic impairment (HI) on the pharmacokinetics and
      safety of imarikiren. METHODS: This phase I, open-label, parallel-group
      comparative study evaluated the pharmacokinetics and safety of a single 40 mg
      oral dose of imarikiren in RI [mild, moderate, severe, or end-stage renal disease
      (ESRD), and on hemodialysis] or HI (mild or moderate) subjects compared with
      subjects with normal renal or hepatic function. RESULTS: Following administration
      of a single 40 mg oral imarikiren dose, the geometric mean imarikiren area under
      the plasma concentration-time curve from time zero to infinity (AUCinfinity) and
      maximum observed plasma concentration (Cmax) in subjects with mild, moderate, and
      severe RI (including non-hemodialysis and ESRD), and hemodialysis subjects
      compared with normal renal function subjects were approximately 0.5-, 1.2-, 2.7-,
      and 1.8-fold, respectively, for AUCinfinity; and approximately 0.6-, 0.8-, 2.1-,
      and 1.4-fold, respectively, for Cmax. The mean fraction of excretion of
      imarikiren in dialysate was ~ 3% during the 4 h dialysis period. The geometric
      mean imarikiren AUCinfinity and Cmax in mild and moderate HI subjects compared
      with normal hepatic function subjects were approximately 1.0- and 1.4-fold,
      respectively, for AUCinfinity, and approximately 0.9- and 1.3-fold, respectively,
      for Cmax. No deaths or serious adverse events were observed; all adverse events
      were mild or moderate in intensity. CONCLUSIONS: RI and HI are associated with
      limited changes in imarikiren pharmacokinetics. Imarikiren was safe and well
      tolerated, regardless of the severity of RI or HI. CLINICAL TRIAL REGISTRATION:
      ClinicalTrials.gov Identifier: NCT02367872.

PMID- 30194586
TI  - Internal mammary lymph node metastases in breast cancer: what should radiologists
      know?
AB  - The internal mammary lymph node (IMLN) chain is a pathway through which breast
      lymphatic drainage flows. The internal mammary lymphatic vessel runs around the
      internal mammary artery and veins with IMLN in the parasternal intercostal
      spaces. IMLN metastasis, which forms a part of clinical TNM staging, may
      negatively affect the prognosis of primary breast cancer patients. IMLN
      metastasis is clinically detected using ultrasound, computed tomography, magnetic
      resonance imaging, and 18F-deoxyglucose positron emission tomography computed
      tomography. The uptake of radioactive tracers in IMLN with clinically negative
      axillary lymph nodes is often identified using sentinel lymph node mapping (SLNM)
      in primary breast cancer patients. The indication for IMLN biopsy or resection
      that is clinically detected or visualized using SLNM is controversial. The
      clinically suspicious IMLN may be considered for ultrasound-guided fine-needle
      aspiration. First IMLN recurrence needs to be biopsied. Irradiation of the
      breast, chest wall, and/or regional nodal irradiation, including IMLN, following
      lumpectomy or postmastectomy is recommended. Although radiation therapy for IMLN
      recurrence may improve clinical outcomes, it is also associated with pulmonary
      and cardiac toxicities. This review covers the local anatomy of IMLN, lymph
      drainage and image findings of IMLN with a discussion.

PMID- 30194588
TI  - Laparoscopic Sleeve Gastrectomy Learning Curve: Clinical and Economical Impact.
AB  - BACKGROUND: The results in the literature regarding the learning curve (LC) of
      laparoscopic sleeve gastrectomy (LSG) are scarce and non-definitive. The purpose
      of the study was to evaluate the correlation between the LSG learning curve and
      intraoperative parameter variation, postoperative morbidity, weight loss results,
      and economic impact. METHODS: The first 99 obese patients undergoing LSG surgery
      by the same surgeon from March 2013 to April 2016 were included in the present
      study. Patients were equally distributed among three groups (A, B, C) based on
      case sequence. RESULTS: The three study groups were homogeneous with respect to
      age, BMI, gender, and comorbidities. There was a significant reduction in
      operative time among the groups (p < 0.00001), with a difference of approximately
      40 min between the first and third groups. The decrease in operative time was
      associated with a decrease in the number of stapler firings used per LSG.
      Conversely, there was no statistical correlation between intraoperative blood
      loss, intraoperative complications, or weight loss 1-year postsurgery and the LSG
      learning curve. In addition, the increase in experience with LSG was also
      associated with a significant reduction (p < 0.00001) in the length of hospital
      stay. With respect to postoperative complications, a statistically significant
      difference was recorded between groups B and C (p = 0.02). Finally, a patient
      undergoing surgery at the end of the LC had an estimated reduction in economic
      impact of approximately 2700 Euros compared with a patient undergoing surgery at
      the beginning of the LC. CONCLUSION: Approximately 60 cases are required to reach
      proficiency in reducing postoperative complications and costs of LSG.

PMID- 30194589
TI  - Adverse Childhood Experiences and Their Relation to Parenting Stress and
      Parenting Practices.
AB  - The objective of this study was to understand the relationship between the early
      adverse childhood experiences (ACEs) of parents and their later parenting stress
      and practices. At the baseline visit of an 8-week course of cognitive behavioral
      therapy, parenting women completed the Parenting Stress Index-Short Form (PSI-SF)
      and the Positive Parenting Practices (PPP) scale. Linear regression procedures
      were used to assess the relationship between a parent's own early experience of
      ACEs and current parenting stress and practices, including if there was a dose
      response relationship. For the PSI-SF, significant dose-response relationships
      were observed between ACEs and the PSI Total Stress score (p < 0.05) and the
      difficult child subscale (p < 0.05). Additionally, a relationship was suggested
      with the parental distress subscale (p < 0.10). No significant relationships were
      found between ACEs and the parent-child dysfunctional interaction subscale of the
      PSI-SF or the PPP scale. Given the association observed between ACEs and
      parenting stress, it is important that future psychosocial interventions and
      policy initiatives preventing ACEs are developed.

PMID- 30194587
TI  - Transient and asymptomatic meningitis in human immunodeficiency virus-1 subtype
      C: a case study of genetic compartmentalization and biomarker dynamics.
AB  - Human immunodeficiency virus (HIV) genetic compartmentalization is defined as
      genetic differences in HIV in different tissue compartments or subcompartments
      that characterize viral quasispecies. This descriptive, longitudinal study
      assessed the dynamics of inflammation, humoral immune response, blood-brain
      barrier, blood-cerebrospinal fluid (CSF) barrier, as well as neuronal injury
      biomarkers in serially obtained CSF and serum samples from an antiretroviral
      (ARV) therapy-naive patient with HIV-1 subtype C with CSF HIV genetic
      compartmentalization that resolved spontaneously without ARV treatment. The first
      CSF sample showed an increase in white blood cell (WBC) count (382 cells/mm3) and
      a marked increase in the levels of inflammatory cytokines and chemokines,
      including tumor necrosis factor (TNF)alpha, interleukin (IL)-10, IP-10, and
      regulated on activation, normal T cell expressed and secreted (RANTES), which
      raise the suspicion of dual infection. Serum sample analysis showed all cytokine
      levels to be normal, with only IP-10 slightly increased. These results
      corroborate the hypothesis that the CNS immunologic response in a patient with
      HIV infection was independent of the systemic immunologic response. The patient
      also had persistently elevated levels of sCD14, neopterin, and beta2M, which were
      strongly suggestive of persistent CNS immunologic stimulation. This report
      describes a patient with HIV subtype C who developed a transient episode of
      asymptomatic HIV meningitis with compartmentalization of HIV in the CSF that
      resolved independently of ARV therapy. Extensive CSF studies were performed as
      part of an ongoing longitudinal study, which revealed CNS immune abnormalities.
      This case presents evidence of HIV-1 subtype C neurotropism and
      compartmentalization.

PMID- 30194590
TI  - Overview of Serpins and Their Roles in Biological Systems.
AB  - Serine protease inhibitors are ubiquitous regulators for a multitude of pathways
      in humans. The serpins represent an ancient pathway now known to be present in
      all kingdoms and often regulating central pathways for clotting, immunity, and
      even cancer in man. Serpins have been present from the time of the dinosaurs and
      can represent a large proportion of circulating blood proteins. With this
      introductory chapter, we present an overview of serpins as well as an
      introduction and overview of the chapters describing the methodology used in the
      new approaches to understanding their molecular mechanisms of action and their
      roles in health and disease.

PMID- 30194591
TI  - Methods for Determining and Understanding Serpin Structure and Function: X-Ray
      Crystallography.
AB  - Deciphering the X-ray crystal structures of serine protease inhibitors (serpins)
      and serpin complexes has been an integral part of understanding serpin function
      and inhibitory mechanisms. In addition, high-resolution structural information of
      serpins derived from the three domains of life (bacteria, archaea, and
      eukaryotic) and viruses has provided valuable insights into the hereditary and
      evolutionary history of this unique superfamily of proteins. This chapter will
      provide an overview of the predominant biophysical method that has yielded this
      information, X-ray crystallography. In addition, details of up-and-coming
      methods, such as neutron crystallography, cryo-electron microscopy, and small-
      and wide-angle solution scattering, and their potential applications to serpin
      structural biology will be briefly discussed. As serpins remain important both
      biologically and medicinally, the information provided in this chapter will aid
      in future experiments to expand our knowledge of this family of proteins.

PMID- 30194592
TI  - Serpin Phage Display: The Use of a T7 System to Probe Reactive Center Loop
      Libraries with Different Serine Proteinases.
AB  - Phage display is a protein engineering approach that involves construction of
      libraries of variant proteins displayed on the surface of bacteriophage as capsid
      fusion proteins and their screening for binding and inhibitory function through
      the use of bait proteins. Recently, we adapted a commercially available T7 phage
      display system to create phage-displayed serpin libraries hypervariable in up to
      five positions in their reactive center loop (RCL). The RCL is a key determinant
      in serpin specificity, the relationship between the structure of a given serpin
      and which target proteinase(s) it inhibits. In this chapter, we describe
      protocols to assess the feasibility of this method for different
      serpin/proteinase combinations and share experience with this technology gathered
      in the course of studying two serpins and multiple proteinases with this powerful
      iterative screening approach.

PMID- 30194593
TI  - Kinetic Measurement of Serpin Inhibitory Activity by Real-Time Fluorogenic
      Biochemical Assay.
AB  - Biochemical fluorogenic and chromogenic assays facilitate real-time study of
      enzyme function. Based on the principle of enzymatic inhibition, these kinetic
      assays can be adapted to measure the function of serpins. Compared to
      traditional, electrophoretic study of serpin inhibitory complex formation,
      kinetic assays allow for finer temporal resolution as well as more quantitative
      comparisons between different conditions. This chapter describes methodology for
      performing real-time, kinetic measurement of serpin inhibitory activity by
      fluorogenic substrate conversion assay. Specifically, the methods covered include
      measurement of alpha-1-antitrypsin inhibitory activity against trypsin and
      heparin-dependent anti-thrombin III inhibitory activity against thrombin. These
      methods are scalable to small-volume, high-density format and can be applied for
      high-throughput screening of serpin activity modulators.

PMID- 30194594
TI  - Methods for Identifying Virus-Derived Serpins.
AB  - The serpin family of serine proteinase inhibitors plays key roles in the
      maintenance of mammalian homeostasis. Virus-encoded serpins disrupt the balance
      of mammalian proteases to facilitate virus replication in the infected host. DNA
      viruses, in particular members of the poxvirus family, have acquired multiple
      copies of the functional serpins which are essential for viral pathogenesis.
      Virus-encoded serpins have proven to be very effective inhibitors of host
      proteases and thus are very attractive candidate molecules as immunomodulatory
      drugs. With this chapter we explain approaches to identifying immune-modulating
      viral serpins.

PMID- 30194595
TI  - In Vitro Approaches for the Assessment of Serpin Polymerization.
AB  - Serpin polymerization is the result of end-to-end ordered aggregation of serpin
      monomers into linear unbranched chains. This change in molecular state represents
      the basis of several conformational diseases with pathological gain-of-function
      and loss-of-function phenotypes, termed serpinopathies. Tools that enable
      quantification and characterization of polymer formation are therefore important
      to the study of serpin behavior in this pathophysiological context. Such methods
      rely on different manifestations of molecular change: polymerization-the
      generation of molecules with increasing molecular weight-is accompanied by
      concomitant structural rearrangements in the constituent subunits. Different
      approaches may be appropriate dependent on whether measurements are made on
      static samples, such as tissue or cell culture extracts, or in time-resolved
      experiments, often undertaken using polymers artificially induced under in vitro
      destabilizing conditions. In the former category, we describe the application of
      polyacrylamide electrophoresis, Western blot, ELISA, and negative-stain electron
      microscopy and in the latter category, Forster resonance energy transfer and
      fluorescence spectroscopy using environment-sensitive probes.

PMID- 30194596
TI  - Cellular Models for the Serpinopathies.
AB  - Our current knowledge about the cellular mechanisms underlying serpin-related
      disorders, the serpinopathies, is predominantly based on studies in cell culture
      models of disease, particularly for alpha-1 antitrypsin (AAT, SERPINA1)
      deficiency causing emphysema and the familial encephalopathy with neuroserpin
      (NS, SERPINI1) inclusion bodies (FENIB). FENIB, a neurodegenerative dementia, is
      caused by polymerization of NS (Miranda and Lomas, Cell Mol Life Sci 63:709-722,
      2006; Roussel BD et al., Epileptic Disor 18:103-110, 2016), while AAT deficiency
      presents as a result of several divergent mutations in the AAT gene that cause
      lack of protein synthesis or complete intracellular degradation (null variants)
      or polymer formation (polymerogenic variants) (Lomas et al., J Hepatol 65:413
      424, 2016; Greene et al., Nat Rev Dis Primers 2:16051, 2016; Ferrarotti et al.
      Orphanet J Rare D 9:172, 2014). Both diseases have been extensively modeled in
      cell culture systems by expressing mutant variants in a variety of ways. Here we
      describe the methodologies we follow in our cell model systems used to examine
      serpin disorders.

PMID- 30194597
TI  - Binding of Serpins to Immobilized Phospholipids and Phospholipids in Suspension.
AB  - Binding of serine protease inhibitors (serpins) to nonprotein ligands such as
      glycosaminoglycans or phospholipids has been shown to modify their inhibitory
      activity and-at least in the case of SERPINA5-to mediate serpin internalization
      into cells. Also phospholipid functions may be altered when bound to serpins or
      other proteins.By interacting with phospholipids, serpins might influence a
      variety of cellular functions. Binding of proteins to phospholipids can be
      studied by several methods. Here we describe solid-phase assays, in which pure
      phospholipids are immobilized on nitrocellulose membranes, PVDF membranes, or
      microtiter plates. Bound proteins are detected with specific antibodies and
      labeled secondary antibodies. We also describe a method visualizing binding of
      phospholipids in suspension by non-denaturing polyacrylamide gel electrophoresis
      (PAGE) followed by Western blotting.

PMID- 30194598
TI  - Viral Serpin Reactive Center Loop (RCL) Peptides: Design and Testing.
AB  - Serpins function as a trap for serine proteases, presenting the reactive center
      loop (RCL) as a target for individual proteases. When the protease cleaves the
      RCL, the serpin and protease become covalently linked leading to a loss of
      function of both the protease and the serpin; this suicide inhibition is often
      referred to as a "mouse trap." When the RCL P1-P1' scissile bond is cut by the
      protease, the resulting bond between the protease and the RCL leads to insertion
      of the cleaved RCL into the beta-sheet A and relocation of the protease to the
      opposite pole of the serpin, forming a suicide complex. Only a relatively small
      part of the serpin molecule can be removed in deletion mutations before the
      serpin RCL inhibitory function is lost. Serpin RCL peptides have been developed
      to block formation of serpin aggregates in serpinopathies, genetic serpin
      mutations wherein the abnormal serpins insert their RCL into adjacent serpins
      forming aggregates of inactive serpins.We have further posited that this natural
      cleavage site in the serpin RCL may form active serpin metabolites with potential
      to add to the serpin's inhibitory functions. We have developed RCL peptides based
      upon predicted serpin RCL cleavage (or metabolism) sites and tested these serpins
      for inhibitory function. In this chapter we describe the development of RCL
      derived peptides, peptides derived based upon the RCL sequences of two
      myxomaviral serpins. Methods used to develop peptides are described for RCL
      derived peptides from Serp-1, a thrombotic and thrombolytic serine protease
      inhibitor, and Serp-2, a cross class serine and cysteine protease inhibitor
      (Subheadings 2.1 and 3.1). Approaches to testing RCL peptide functions, in vitro
      by molecular assays and in vivo in models of cell migration, MHV-68 infection,
      and aortic allograft transplant are described (Subheadings 2.2 and 3.2).

PMID- 30194599
TI  - In Vivo Analysis of Alpha-1-Antitrypsin Functions in Autoimmune Disease Models.
AB  - Alpha-1-antitrypsin (AAT) is a circulating protein, a serpin, with multiple
      protective functions. Beside the well-known proteinase inhibitory function, which
      protects the lungs from chronic obstructive pulmonary disease (COPD), many
      studies have shown that AAT inhibits pro-inflammatory cytokine gene expression
      and functions. These anti-inflammatory and immune-regulatory properties have led
      to studies testing the therapeutic effect of AAT in autoimmune disease models.
      Initially, a study using recombinant adeno-associated viral (rAAV) vector showed
      that AAT gene therapy prevented type 1 diabetes (T1D) development in a nonobese
      diabetic (NOD) mouse model. Consequently, several studies confirmed that AAT
      therapy prevented and reversed T1D. AAT therapy has also been tested and has
      demonstrated protective effects in a collagen-induced arthritis model and a
      systemic lupus erythematosus (SLE) mouse model. This chapter describes methods
      that evaluate AAT functions in autoimmune mouse models.

PMID- 30194600
TI  - Analysis of In Vivo Serpin Functions in Models of Inflammatory Vascular Disease.
AB  - Serpins have a wide range of functions in regulation of serine proteases in the
      thrombotic cascade and in immune responses, representing up to 2-10% of
      circulating proteins in the blood. Selected serpins also have cross-class
      inhibitory actions for cysteine proteases in inflammasome and apoptosis pathways.
      The arterial and venous systems transport blood throughout the mammalian body
      representing a central site for interactions between coagulation proteases and
      circulating blood cells (immune cells) and target tissues, a very extensive and
      complex interaction. While analysis of serpin functions in vitro in kinetics or
      gel shift assays or in tissue culture provides very necessary information on
      molecular mechanisms, the penultimate assessment of biological or physiological
      functions and efficacy for serpins as therapeutics requires study in vivo in
      whole animal models (some also consider cell culture to be an in vivo
      approach).Mouse models of arterial transplant with immune rejection as well as
      models of inflammatory vasculitis induced by infection have been used to study
      the interplay between the coagulation and immune response pathways. We describe
      here three in vivo vasculitis models that are used to study the roles of serpins
      in disease and as therapeutics. The models described include (1) mouse aortic
      allograft transplantation, (2) human temporal artery (TA) xenograft into
      immunodeficient mouse aorta, and (3) mouse herpes virus (MHV68)-induced
      inflammatory vasculitis in interferon-gamma receptor (IFNgammaR) knockout mice.

PMID- 30194601
TI  - Gene Delivery of Alpha-1-Antitrypsin Using Recombinant Adeno-Associated Virus
      (rAAV).
AB  - The challenge for alpha-1-antitrypsin (AAT also known as SERPINA1) gene therapy
      is to achieve long term and high levels of AAT production. Recombinant adeno
      associated virus (rAAV) vector has several advantages for AAT gene delivery
      including no viral genes in the vector, no requirement of integration for long
      term transgene expression, low immunogenicity, and wide tropism. AAV-mediated AAT
      gene therapy has been developed and tested in animal models for AAT deficiency,
      type 1 diabetes, rheumatoid arthritis, and osteoporosis. AAV-mediated AAT gene
      therapy has also been tested in clinical studies and has shown promising results.
      Here we describe the methods of rAAV-AAT vector construction and production as
      well as AAT gene delivery through (1) liver-directed, (2) muscle-directed, and
      (3) mesenchymal stem cell (MSC)-mediated routes. We will also describe methods
      for the evaluation of AAT expression for each delivery approach.

PMID- 30194602
TI  - Serpins in Venous Thrombosis and Venous Thrombus Resolution.
AB  - Several serpins function as potent inhibitors of thrombolytic serine proteases.
      Venous thrombosis is a common and debilitating condition whose incidence is on
      the rise. Studies using genetically modified mice and inhibitors have shown that
      the plasminogen activator inhibitors (PAI), PAI-1 and PAI-2, are primary
      regulators of plasminogen activation and contribute to regulating the resolution
      of experimental venous thrombi, via inflammatory mechanisms, vascular remodeling,
      and inhibition of fibrinolysis. Therapies to accelerate venous thrombus
      resolution would be beneficial, since delayed or incomplete clot resolution
      frequently leads to postthrombotic syndrome, a long-term complication associated
      with debilitating limb swelling, pain, and recurrent skin ulceration. Here we
      describe a useful and reproducible mouse model for the study of venous thrombus
      resolution involving ligation of the inferior vena cava and elucidation of the
      molecular and cellular determinants of venous thrombus formation and resolution.

PMID- 30194603
TI  - Next-Generation Sequencing Library Preparation for 16S rRNA Microbiome Analysis
      After Serpin Treatment.
AB  - Serine protease inhibitors, serpins, can have profound effects on many systems in
      the body including immune defense systems. The microbiome, specifically the gut
      and lung bacterial microbiota, is now known, under some conditions, to alter
      immune defenses. DNA library preparation for microbiome studies is a procedure
      that prepares microbial genomic DNA to be sequenced in next-generation sequencing
      platforms. The construction involves a PCR reaction that will amplify the 16S
      rRNA gene and will incorporate a specific index and adaptors to the fragments.
      After confirmation of the product amplification by gel electrophoresis, samples
      will be later normalized to the same DNA amount of 240 ng. Final concentration of
      the library is validated by quantitative PCR (qPCR).Here we describe methods to
      analyze changes in the microbiome after treatment with immune-modulating agents,
      specifically serpins.

PMID- 30194604
TI  - Methods for Assessing Serpins as Neuroprotective Therapeutics.
AB  - As the systematic work on the pathogenesis of the white matter injury in the
      spinal cord models progresses, it becomes obvious that a severe and
      extraordinarily protracted, destructive inflammation follows the initial injury.
      Appropriate anti-inflammatory therapies of sufficient duration should not only
      inhibit but also lead to the elimination of this destructive inflammation, thus
      resulting in neuroprotection of the spinal cord tissue and a greater preservation
      of the neurologic function. While dexamethasone, a powerful, anti-inflammatory
      steroid analog administered continuously by subdural infusion for 7 days
      inhibited severe macrophage infiltration in the cavity of injury, the dose used
      was remarkably toxic. A 2-week-long infusion of lower doses of dexamethasone
      resulted in dose-dependent inhibition of macrophage infiltration and was better
      tolerated by the rats, but it became evident that a much longer duration of
      subdural administration of a powerful anti-inflammatory drug is required to
      eliminate myelin-rich, necrotic debris from the cavity and synthetic steroids
      such as dexamethasone, and methylprednisolone may be too toxic for this
      application. Therefore, nontoxic but powerful anti-inflammatory compounds are
      required for neuroprotective treatment of the spinal cord injury (SCI) and also
      brain trauma and stroke where the massive injury to the white matter occurs.
      Serpins have been associated with neurological damage. The mammalian serpin
      neuroserpin (SERPINI1) is reported to act in a protective manner after
      cerebrospinal infarction. The serine protease, tissue-type plasminogen activator
      (tPA), and the serpin plasminogen activator inhibitor (PAI-1, SERPINE1) are both
      upregulated at sites of central nervous system damage. In preliminary studies,
      subdural infusion of the myxomaviral serpin, Serp-1, resulted in the powerful
      inhibition of the macrophage infiltration of the cavity of injury, comparable to
      the inhibition by high dose of dexamethasone that has proven to be unduly toxic.
      Nontoxic, yet powerful neuroprotective, anti-inflammatory effects of Serp-1 may
      indicate this serpin protein as a potential attractive compound to treat SCI and
      similar syndromes involving massive injury to the white matter such as brain
      trauma and stroke. Novel methods of drug delivery, chronic subdural infusion, and
      novel analytic methods to measure the effectiveness of the neuroprotective serpin
      treatments are discussed in this chapter.

PMID- 30194605
TI  - Adeno-Associated Virus Delivery of Viral Serpins for Ocular Diseases: Design and
      Validation.
AB  - Adeno-associated virus (AAV) has become the preferred viral gene transfer
      platform for ocular gene therapy due to its known safety profile in human
      clinical trials. This viral vector has a 4.7 kbp (kilo base pair) carrying
      capacity (single-stranded DNA) and only retains the inverted terminal repeats
      (ITRs) from the original virus. Here we describe the design and testing of AAV
      vectors capable of delivering an anti-inflammatory serine protease inhibitor
      (serpin) derived from the myxoma virus. Myxoma is a rabbit species specific virus
      infection, a Leporipoxvirus. Myxomaviral proteins have been developed as
      therapeutic stand-alone immune-modulating proteins for inflammation-based
      disorders and the myxoma virus itself is under development as a viral oncolytic
      platform for cancer treatment. We fused the Serp2 gene with the GFP reporter gene
      through a self-cleaving peptide.

PMID- 30194606
TI  - Serpins: Development for Therapeutic Applications.
AB  - Serine protease inhibitors, or serpins, function as central regulators for many
      vital processes in the mammalian body, maintaining homeostasis for clot formation
      and breakdown, immune responses, lung function, and hormone or central nervous
      system activity, among many others. When serine protease activity or serpin
      mediated regulation becomes unbalanced or dysfunctional, then severe disease
      states and pathogenesis can ensue. With serpinopathies, genetic mutations lead to
      inactive serpins or protein aggregation with loss of function. With other
      disorders, such as sepsis, atherosclerosis, cancer, obesity, and the metabolic
      syndrome, the thrombotic and thrombolytic cascades and/or inflammatory responses
      become unbalanced, with excess bleeding and clotting and upregulation of adverse
      immune responses. Returning overall balance can be engineered through
      introduction of a beneficial serpin replacement as a therapeutic or through
      blockade of serpins that are detrimental. Several drugs have been developed and
      are currently in use and/or in development both to replace dysfunctional serpins
      and to block adverse effects induced by aberrant protease or serpin actions.With
      this chapter, we provide a general overview of the development of a virus-derived
      serpin, Serp-1, and serpin reactive center loop (RCL) peptides, as therapeutics.
      Serp-1 is a virus-derived serpin developed as a new class of immune modulator. We
      will use the development of Serp-1 as a general introduction to serpin-based drug
      development.

PMID- 30194608
TI  - Recurrence Risk Based on Pathologic Stage After Neoadjuvant Chemoradiotherapy in
      Esophageal Squamous Cell Carcinoma: Implications for Risk-Based Postoperative
      Surveillance Strategies.
AB  - BACKGROUND: This study aimed to investigate the association between pathologic
      stage and recurrence risk and survival for patients with esophageal squamous cell
      carcinoma (SCC) after neoadjuvant chemoradiotherapy (CRT). METHODS: This
      retrospective analysis consisted of two patient cohorts who had esophageal SCC
      treated with neoadjuvant CRT and esophagectomy at two major academic institutions
      between 2002 and 2015. The study included 174 patients in the training cohort and
      51 patients in the validation cohort. Recurrence pattern, frequency, and survival
      according to pathologic stage were analyzed. RESULTS: After surgery, patients in
      the training cohort had the following pathologic categories: stage 0 (44.8%, n =
      78), stage 1 (6.9%, n = 12), stage 2 (35.6%, n = 62), and stage 3 (12.6%, n =
      22). During a median follow-up period of 53.9 months, recurrences developed in 59
      patients. The recurrence rates were 22.2% for stages 0 and 1, 38.7% for stage 2,
      and 68.2% for stage 3 (stages 0 and 1 vs. stage 2 [P = 0.028], stages 0 and 1 vs.
      stage 3 [P < 0.001], and stage 2 vs. stage 3 [P = 0.017]). More than 20% of
      patients with stages 0 and 1 or 2 disease experienced late relapses after 3 years
      of follow-up evaluation, whereas all the patients with pathologic stage 3 had
      recurrences within 2 years. The 5-year recurrence-free survival rate was 74.7%
      for the patients with pathologic stage 0 or 1, 61.4% for those with stage 2, and
      20.9% for those with stage 3 disease (P < 0.001). These major findings were
      successfully reproduced in the Western validation cohort. CONCLUSIONS: Patients
      with a higher pathologic stage were associated with a significantly higher risk
      of recurrences and worse survival. Multicenter and prospective validation is
      warranted.

PMID- 30194607
TI  - The detection of age-, gender-, and region-specific changes in mouse brain
      tocopherol levels via the application of different validated HPLC methods.
AB  - The aging process clearly increases the demand for antioxidant protection,
      especially in the brain, involving that provided by alpha-tocopherol (alphaT).
      However, little is known about the age-related changes in brain alphaT levels and
      the influencing effect of gender on it, in human or murine samples as well.
      Accordingly, the aim of the current study was to detect age-, gender- and region
      specific changes in alphaT concentrations in mouse brain tissue and to assess the
      influencing effect of plasma alphaT levels on it. Female and male C57BL/6 mice at
      the ages of 6, 16 and 66 weeks (n = 9 in each group) were applied. alphaT levels
      were determined with high performance liquid chromatography (HPLC) from the
      striatum, cortex, hippocampus, cerebellum, brainstem and from plasma samples. A
      detailed validation process was carried out for the applied HPLC method as well.
      The results demonstrated that brain alphaT levels significantly increased in the
      striatum, cortex, and hippocampus with aging in both genders, but in a more
      pronounced way in females with an increasing magnitude of this difference. In
      case of the cerebellum, a moderate elevation could be detected only in females,
      whereas in case of the brainstem there was no significant change in alphaT level.
      With regard to plasma samples, no clear trend could be identified. The current
      study is the first to present age-dependent gender-specific changes in alphaT
      level in certain brain regions of the C57Bl/6 mouse strain, and may provide
      meaningful information for future therapeutic studies targeting aging-related
      processes.

PMID- 30194609
TI  - [Coercive interventions: historical summary and review of subjective experience].
AB  - Psychiatric treatment has always been associated with violence and coercion.
      Involuntary admission and coercive measures are still frequently occurring
      components in everyday clinical practice.Up to 15% of psychiatric inpatients
      experience coercive treatment at least once during hospital stay. Particularly
      patients suffering from schizophrenia, organic mental disorders and mania have a
      high risk for such incidents.There is an ongoing intense debate on the need and
      justification of coercive measures, although most clinicians and scientists
      currently agree that there is no alternative. Several investigations have shown
      that seclusion and mechanical restraint go along with physical and psychological
      problems affecting both, patients and staff. However, it was possible to identify
      aspects that could be improved: Maintaining an objective and professional
      communication during coercive treatment seems just as important as making
      comprehensible decisions. Alternative treatment options should be focus of
      further investigations.

PMID- 30194610
TI  - Orthodontic extrusion of an incisor with a complicated crown root fracture,
      utilising a custom-made intra-canal wire loop and endodontic treatment: a case
      report with 7-years follow-up.
AB  - BACKGROUND: Dental trauma is very common among children. Crown fractures
      represent the majority of dental trauma in the permanent dentition. Complicated
      crown-root fractures require a multidisciplinary approach, for long-term success.
      CASE REPORT: The multidisciplinary treatment of a traumatised permanent upper
      incisor of an 11-year-old patient that sustained a complicated crown root
      fracture, while under active orthodontic treatment is presented. The pulp was
      widely exposed and therefore endodontic treatment was necessary. However most of
      the crown (and part of the coronal part of the root as well) had been fractured
      and the tooth could not be properly isolated for an aseptic procedure. METHODS:
      Orthodontic extrusion was decided and it was achieved using a custom-made, intra
      canal wire loop that was cemented in the root canal and attached to the patients'
      orthodontic fixed appliances. RESULTS: The remaining tooth structure was
      successfully extruded coronally and following endodontic treatment (under proper
      rubber dam isolation [RDI]), root canal obturated using the cold gutta-percha
      technique (in order to avoid further trauma to the periodontal ligament, if a
      warm obturation technique was chosen) and subsequently restored under RDI. At the
      7-years follow-up, no signs of clinical or radiographical inflammation were
      evident. CONCLUSIONS: A custom wire loop as an anchoring site is an easy-to-adopt
      and-perform option for such cases. Cold gutta-percha obturation techniques should
      be opted for root canal obturation to avoid further trauma to the periodontal
      ligament.

PMID- 30194612
TI  - A Generic Model for Quantitative Prediction of Interactions Mediated by Efflux
      Transporters and Cytochromes: Application to P-Glycoprotein and Cytochrome 3A4.
AB  - BACKGROUND AND OBJECTIVE: The In Vivo Mechanistic Static Model (IMSM) is a
      powerful method used to predict the magnitude of drug-drug interactions (DDIs)
      mediated by cytochromes. The objective of this study was to extend the IMSM
      paradigm to DDIs mediated by efflux transporters and cytochromes. METHODS: First,
      a generic model for this kind of interaction was devised. A flexible approach was
      then developed to estimate the characteristic parameters [the contribution ratios
      (CRs) and inhibition or induction potencies (IXs)] from clinical data by non
      linear regression. Next, this approach was applied to the DDIs mediated by P
      glycoprotein (P-gp) and cytochrome P450 (CYP) 3A4/3A5 in a large set of victim
      drugs and interactors. Lastly, the model and associated parameters were used to
      identify the DDIs most at risk of overexposure. RESULTS: A total of 25 substrates
      and 26 interactors (three inducers, 23 inhibitors) could be considered in the
      regression analysis. The number of observations [area under the plasma
      concentration-time curve ratios or renal clearance ratios (Robs)] was 138. Fifty
      CRs and 57 IXs were estimated. The proportions of predictions within 0.67- to 1.5
      fold Robs and within 0.5- to 2-fold Robs were 79% and 93% for the internal
      validation and 76% and 88% for the external validation, respectively. The median
      fold error was 0.98 (the ideal value is 1) and the interquartile range of the
      fold error was 0.36. The relative standard error of parameter estimates was a
      maximum of 15%. CONCLUSIONS: The IMSM approach was successfully extended to DDIs
      mediated by P-gp and CYP3A4/3A5. The method revealed good predictive performances
      by internal and external validation.

PMID- 30194613
TI  - The Association Between Muslim Religiosity and Internet Addiction Among Young
      Adult College Students.
AB  - The major focus of this research was to investigate the effects of religiosity
      factor on internet addiction among young adults enrolled at college level. We
      adopted two instruments to gather the information including OK-religious attitude
      scale for Muslims developed and used by Ok, Uzeyir, and Internet Addiction Test
      prepared by Widyanto and McMurran. In total, 800 Muslim college students enrolled
      in four colleges at graduate level of southern Punjab Pakistan were chosen
      through multi-phase sampling. The subscales revealed more than .76 Cronbach alpha
      coefficients. The outcomes expressed positive role in case of DE conversion in
      world faith toward internet indications, whereas intrinsic religious orientations
      remained beneficial in decreasing internet usage. Students' anti-religion
      subscale demonstrates higher increase in becoming of internet addict; however,
      intrinsic religious orientations show significant decrease in using internet.
      Similarly, DE conversion in world faith view and Anti-Religion Scale indicate
      students' significant contributions in expecting them being internet addict. The
      study determines that the religiosity factor considerably illuminate the
      variances in developing internet addiction among the Muslim college adults with
      the direct effect of intrinsic religious orientation and indirect effect of anti
      religion aspect.

PMID- 30194611
TI  - Procedural pain in routine dental care for children: a part of the Swedish BITA
      study.
AB  - AIM: To investigate the frequency and reported intensity levels of dental
      treatment pain and discomfort in children, in conjunction with regular dental
      visits. METHODS: The study included 2363 children in four different age cohorts.
      Data was collected from structured interviews by dental personnel regarding pain
      experiences or discomfort after treatments, including analgesia, extractions,
      operative treatments and radiographic examinations. RESULTS: One-third of all
      treatment occasions were experienced as painful and/or causing discomfort.
      Treatment sessions including analgesia were assessed as painful in 49.7% of
      occasions, with injection being the most common given reason for pain. Extraction
      was painful in 62.4% of occasions, with injection as the main reason for pain.
      Operative treatments were assessed as painful in 38.8% of occasions, with
      drilling as the most common reason for pain and discomfort. Pain was reported in
      approximately 19% of all radiographic examinations. CONCLUSIONS: Injection was
      the major reason for pain during treatment, including injection and extraction,
      while drilling was the most common cause of pain during restorative treatment.
      Dentists should try to minimise the experience of pain and discomfort by using
      all available measures to perform pain-free and effective dental injections.

PMID- 30194615
TI  - Abstracts of the 51st Annual ESPN Meeting, Antalya, October 2018.

PMID- 30194614
TI  - Brain Machine Interfaces for Vision Restoration: The Current State of Cortical
      Visual Prosthetics.
AB  - Loss of vision alters the day to day life of blind individuals and may impose a
      significant burden on their family and the economy. Cortical visual prosthetics
      have been shown to have the potential of restoring a useful degree of vision via
      stimulation of primary visual cortex. Due to current advances in electrode design
      and wireless power and data transmission, development of these prosthetics has
      gained momentum in the past few years and multiple sites around the world are
      currently developing and testing their designs. In this review, we briefly
      outline the visual prosthetic approaches and describe the history of cortical
      visual prosthetics. Next, we focus on the state of the art of cortical visual
      prosthesis by briefly explaining the design of current devices that are either
      under development or in the clinical testing phase. Lastly, we shed light on the
      challenges of each design and provide some potential solutions.

PMID- 30194616
TI  - Achieving the "ideal" family size at advanced reproductive ages through oocyte
      cryopreservation.

PMID- 30194617
TI  - Detailed endometrial immune assessment of both normal and adverse reproductive
      outcome populations.
AB  - PURPOSE: Using a comprehensive flow cytometric panel, do endometrial immune
      profiles in adverse reproductive outcomes such as repeat implantation failure
      (RIF) and repeat pregnancy loss (RPL) differ from each other and male-factor
      controls? METHODS: Six-hundred and twelve patients had an endometrial biopsy to
      assess the immunophenotype. History on presentation was used to subdivide the
      population into recurrent implantation failure (RIF) [n = 178], recurrent
      pregnancy loss (RPL) [n = 155], primary infertility [n = 130] and secondary
      infertility [n = 114]. A control group was utilised for comparative purposes [n =
      35] and lymphocyte subpopulations were described. RESULTS: Distinct lymphocyte
      percentage differences were noted across the populations. Relative to controls
      and RPL, patients with a history of RIF had significantly raised uterine NKs
      (53.2 vs 45.2 & 42.9%, p < 0.0001). All sub-fertile populations had increased
      percentage peripheral type NKs (p = 0.001), and exhibited increased CD69+
      activation (p = 0.005), higher levels of B cells (p < 0.001), elevated CD4:CD8
      ratio (p < 0.0001), lower T-regs (p = 0.034) and a higher proportion of Th1+ CD4s
      (p = 0.001). Patient aetiology confers some distinct findings, RPL; pNK, Bcells
      and CD4 elevated; RIF; uNK and CD56 raised while CD-8 and NK-T lowered.
      CONCLUSIONS: Flow cytometric endometrial evaluation has the ability to provide a
      rapid and objective analysis of lymphocyte subpopulations. The findings show
      significant variations in cellular proportions of immune cells across the patient
      categories relative to control tissue. The cell types involved suggest that a
      potential differential pro-inflammatory bias may exist in patients with a history
      of adverse reproductive outcomes. Immunological assessment in appropriate
      populations may provide insight into the underlying aetiology of some cases of
      reproductive failure.

PMID- 30194618
TI  - Comparison of sonohysterography to hysterosalpingogram for tubal patency
      assessment in a multicenter fertility treatment trial among women with polycystic
      ovary syndrome.
AB  - PURPOSE: To compare saline infusion sonohysterography (SIS) versus
      hysterosalpingogram (HSG) for confirmation of tubal patency. METHODS: Secondary
      analysis of a randomized controlled trial, Pregnancy in Polycystic Ovary Syndrome
      II (PPCOS II). Seven hundred fifty infertile women (18-40 years old) with
      polycystic ovary syndrome (PCOS) were randomized to up to 5 cycles of letrozole
      or clomiphene citrate. Prior to enrollment, tubal patency was determined by HSG,
      the presence of free fluid in the pelvis on SIS, laparoscopy, or recent
      intrauterine pregnancy. Logistic regression was conducted in patients who
      ovulated with clinical pregnancy as the outcome and HSG or SIS as the key
      independent variable. RESULTS: Among women who ovulated, 414 (66.9%) had tubal
      patency confirmed by SIS and 187 (30.2%) had at least one tube patent on HSG.
      Multivariable analysis indicated that choice of HSG versus SIS did not have a
      significant relationship on likelihood of clinical pregnancy, after adjustment
      for treatment arm, BMI, duration of infertility, smoking, and education (OR 1.14,
      95% CI 0.77, 1.67, P = 0.52). Ectopic pregnancy occurred more often in women who
      had tubal patency confirmed by HSG compared to SIS (2.8% versus 0.6%, P = 0.02).
      CONCLUSIONS: In this large cohort of women with PCOS, there was no significant
      difference in clinical pregnancy rate between women who had tubal patency
      confirmed by HSG versus SIS. SIS is an acceptable imaging modality for assessment
      of tubal patency in this population.

PMID- 30194619
TI  - Changes in public trust in physicians: empirical evidence from China.
AB  - Studies examining the trends in public trust in physicians have provided a
      considerable amount of valuable policy implications for policymakers compared
      with cross-sectional studies on this topic in many countries. This study
      investigated changes in public trust in physicians in China based on two cross
      sectional national surveys conducted in 2011 and 2016 and identified the
      determinants of these changes. The results indicated 83.4% of respondents in 2011
      reported trust or strong trust in physicians in China, which decreased to 64.2%
      by 2016. The results of ordinal logistic regression demonstrated that public
      trust in physicians in China had decreased significantly from 2011 to 2016 (P<
      0.001) after adjusting for other independent variables. Self-reported health
      status, self-rated happiness, and self-identified social class were all
      associated positively with public trust in physicians in China. The results also
      confirmed that decreasing public satisfaction with the most recent treatment
      experience was the major determinant of decreasing public trust in physicians in
      China. The findings of this study suggest that decreasing public trust in
      physicians deserves considerable attention from national policymakers and that
      improving satisfaction with treatment experiences would be the most effective
      strategy for enhancing public trust in physicians in China.

PMID- 30194620
TI  - Inappropriate Prescribing in Elderly Inpatients at a University Hospital in Saudi
      Arabia.
AB  - BACKGROUND AND OBJECTIVES: Elderly populations usually use more medications than
      any other age group and are therefore more susceptible to potentially
      inappropriate prescribing (PIP), drug-drug interactions, and the related health
      consequences. In this study, we aimed to determine PIP prevalence and explore the
      most common potentially inappropriate medications (PIMs) prescribed. METHODS:
      This was a retrospective study involving elderly patients admitted at King
      Abdulaziz Medical City-Jeddah (KAMC-JD), between November 2014 and January 2015.
      We included all elderly patients aged 60 years and above admitted to KAMC-JD
      through the emergency department (ED), clinic, and direct admissions during the
      study period. Patients admitted to the intensive care unit, oncology department,
      and/or those who passed way in the ED before admission were excluded from the
      study. Prescriptions were assessed for PIP using the 2012 Beers Criteria, which
      categorizes PIMs to three classes: first class are medications to avoid in older
      adults regardless of their conditions; second class are medications to avoid with
      certain diseases or syndromes; and third class are medications that should be
      used with caution. RESULTS: Our study included 135 patients, of which 49.6% were
      males. The mean age was 71.26 +/- 8.1 years. According to the 2012 Beers
      Criteria, 80% of patients were using at least one listed PIM. For the Criteria's
      first, second, and third classes, PIM prescription rates were 72.6%, 59.2%, and
      37.7%, respectively. Regarding the most prescribed PIM in each class, insulin
      (sliding scale) was the most reported PIM in the first class, NSAIDs in the
      second class, and, lastly, vasodilators in the third class. CONCLUSION: PIP is a
      serious health issue threatening elderly patients. There is a need to develop
      evidence-based, context-sensitive, and user-friendly tools to assess PIP, as well
      as supportive training programs.

PMID- 30194621
TI  - Selection for encoding: No evidence of better endogenous orienting following
      forget than following remember instructions.
AB  - In an item-method directed forgetting task, attentional resources are withdrawn
      from forget item processing (e.g., Taylor & Fawcett in Attention, Perception, &
      Psychophysics, 73, 1790-1814, 2011). Taylor and Hamm (Attention, Perception, &
      Psychophysics, 78, 168-186, 2016) demonstrated that there is no corresponding
      increase in the proclivity for exogenous attention to be captured following a
      forget instruction. This means either that the attentional resources withdrawn
      from the forget item are reallocated immediately (and therefore not especially
      vulnerable to capture) or that it is not exogenous attention that is withdrawn.
      Given that endogenous attention is distinct from exogenous attention, we
      therefore extended the Taylor and Hamm study by using endogenous orienting rather
      than exogenous orienting. Words appeared individually in a peripheral location
      (Exp. 1) or in a central location (Exp. 2), followed by an instruction to either
      remember or forget. After a short (50-ms) or long (250-ms) interstimulus interval
      (ISI), a central cue (80% accurate) directed participants to allocate their
      attention to the left or right. This was followed by a discrimination target that
      appeared at a 1,000-ms cue-target stimulus onset asynchrony. A subsequent yes-no
      recognition test assessed memory for all study items. In both experiments, we
      observed better recognition of remember words than forget words-a directed
      forgetting effect. We also found a cueing effect, revealed as faster reaction
      times to discriminate cued targets than to discriminate uncued targets. There was
      not, however, an effect of memory instruction (and/or instruction-cue ISI) on the
      magnitude of this cueing effect. Thus, neither exogenous attention nor endogenous
      attention remains in an unengaged state following an instruction to forget.

PMID- 30194622
TI  - Ribociclib with an Aromatase Inhibitor for Previously Untreated, HR-Positive,
      HER2-Negative, Locally Advanced or Metastatic Breast Cancer: An Evidence Review
      Group Perspective of a NICE Single Technology Appraisal.
AB  - The National Institute for Health and Care Excellence, as part of the institute's
      single technology appraisal process, invited the manufacturer of ribociclib
      (Kisqali(r), Novartis) to submit evidence regarding the clinical and cost
      effectiveness of the drug in combination with an aromatase inhibitor for the
      treatment of previously untreated, hormone receptor-positive, human epidermal
      growth factor receptor 2-negative, locally advanced or metastatic breast cancer.
      Kleijnen Systematic Reviews Ltd and Erasmus University Rotterdam were
      commissioned as the Evidence Review Group for this submission. The Evidence
      Review Group reviewed the evidence submitted by the manufacturer, corrected and
      validated the manufacturer's decision analytic model, and conducted exploratory
      analyses to assess the robustness and validity of the presented clinical and cost
      effectiveness results. This article describes the company submission, the
      Evidence Review Group assessment and National Institute for Health and Care
      Excellence subsequent decisions. The main clinical effectiveness evidence was
      obtained from the MONALEESA-2 trial, a randomised controlled trial comparing
      ribociclib plus letrozole with placebo plus letrozole. Progression-free survival
      was significantly longer in the ribociclib group (95% confidence interval, 19.3
      not reached) vs. 14.7 months (95% confidence interval 13.0-16.5) in the placebo
      group. To assess the cost effectiveness of ribociclib in combination with an
      aromatase inhibitor, the company developed an individual patient-level model
      using a discrete-event simulation approach in Microsoft(r) Excel. In the model,
      simulated patients move through a series of three health states until death, i.e.
      first-line progression-free survival, second-line progression-free survival and
      progressive disease. The length of progression-free survival during the first
      line was informed by the MONALEESA-2 trial. The benefit in progression-free
      survival in the first line was transferred to a benefit in overall survival
      assuming full progression-free survival to overall survival surrogacy (because of
      the immaturity of overall survival data from the MONALEESA-2 trial). Patient
      level data from the BOLERO-2 trial, evaluating the addition of everolimus to
      exemestane in the second-line treatment of postmenopausal HR-positive advanced
      breast cancer, were used to inform the length of progression-free survival during
      the second line. Costs included in the model were treatment costs (e.g.
      technology acquisition costs of first, second, third and/or later line
      treatments), drug administration costs, monitoring costs and health state costs
      (including terminal care). Additionally, the costs of adverse events associated
      with the first-line treatment were incorporated. The Evidence Review Group
      recalculated the incremental cost-effectiveness ratio using data from a different
      data cut-off date from the MONALEESA-2 trial and by changing some assumptions
      (e.g. progression-free survival to overall survival surrogacy approach and post
      progression third and/or later line treatment-related costs). After two appraisal
      committee meetings and a revised base case submitted by the company (including a
      second enhanced patient access scheme discount), the committee concluded that
      taking into account the uncertainties in the calculation of the cost
      effectiveness, there were plausible cost-effectiveness estimates broadly in the
      range that could be considered as a cost-effective use of National Health Service
      resources. Therefore, ribociclib was recommended as a treatment option for the
      first-line treatment of hormone receptor-positive, human epidermal growth factor
      receptor 2-negative breast cancer, contingent on the company providing ribociclib
      with the discount agreed in the second enhanced patient access scheme.

PMID- 30194623
TI  - Cost-Effectiveness Analysis of Patiromer and Spironolactone Therapy in Heart
      Failure Patients with Hyperkalemia.
AB  - BACKGROUND AND OBJECTIVE: Certain patients with heart failure (HF) are unable to
      tolerate spironolactone therapy due to hyperkalemia. Patiromer is a novel agent
      used to treat hyperkalemia and has been shown to be efficacious, safe, and well
      tolerated. The potential clinical outcomes and economic value of using patiromer
      and spironolactone in patients with HF unable to otherwise tolerate
      spironolactone due to hyperkalemia are unclear. The objective of this analysis
      was to model the potential pharmacoeconomic value of using patiromer and
      spironolactone in patients with a history of hyperkalemia that prevents them from
      utilizing spironolactone. METHODS: We performed a cost-effectiveness analysis of
      treatment with patiromer, spironolactone, and an angiotensin-converting enzyme
      inhibitor (ACEI) in patients with New York Heart Association (NYHA) class III-IV
      HF compared with ACEI alone. A Markov model was constructed to simulate a cohort
      of 65-year-old patients diagnosed with HF from the payer perspective across the
      lifetime horizon. Clinical inputs were derived from the RALES and OPAL-HK
      randomized trials of spironolactone and patiromer, respectively. Utility
      estimates and costs were derived from the literature and list prices. Outcomes
      assessed included hospitalization, life expectancy, and quality-adjusted life
      years (QALYs), costs, and the incremental cost-effectiveness ratio (ICER). One
      way and probability sensitivity analyses were performed to test the robustness of
      the model findings. RESULTS: Treatment with patiromer-spironolactone-ACEI was
      projected to increase longevity compared with ACEI alone (5.29 vs. 4.62 life
      years gained, respectively), greater QALYs (2.79 vs. 2.60), and costs (US$28,200
      vs. US$18,200), giving an ICER of US$52,700 per QALY gained. The ICERs ranged
      from US$40,000 to US$85,800 per QALY gained in 1-way sensitivity analyses.
      CONCLUSION: Our results suggest that the use of spironolactone-patiromer-ACEI may
      provide clinical benefit and good economic value in patients with NYHA class III
      IV HF unable to tolerate spironolactone due to hyperkalemia.

PMID- 30194624
TI  - One Method, Many Methodological Choices: A Structured Review of Discrete-Choice
      Experiments for Health State Valuation.
AB  - BACKGROUND: Discrete-choice experiments (DCEs) are used in the development of
      preference-based measure (PBM) value sets. There is considerable variation in the
      methodological approaches used to elicit preferences. OBJECTIVE: Our objective
      was to carry out a structured review of DCE methods used for health state
      valuation. METHODS: PubMed was searched until 31 May 2018 for published
      literature using DCEs for health state valuation. Search terms to describe DCEs,
      the process of valuation and preference-based instruments were developed. English
      language papers with any study population were included if they used DCEs to
      develop or directly inform the production of value sets for generic or condition
      specific PBMs. Assessment of paper quality was guided by the recently developed
      Checklist for Reporting Valuation Studies. Data were extracted under six
      categories: general study information, choice task and study design, type of
      designed experiment, modelling and analysis methods, results and discussion.
      RESULTS: The literature search identified 1132 published papers, and 63 papers
      were included in the review. Paper quality was generally high. The study design
      and choice task formats varied considerably, and a wide range of modelling
      methods were employed to estimate value sets. CONCLUSIONS: This review of DCE
      methods used for developing value sets suggests some recurring limitations, areas
      of consensus and areas where further research is required. Methodological
      diversity means that the values should be seen as experimental, and users should
      understand the features of the value sets produced before applying them in
      decision making.

PMID- 30194625
TI  - Risk factors and quality of life of patients with high diabetes-related distress
      in primary care: a cross-sectional, multicenter study.
AB  - PURPOSE: This study aimed to examine risk factors and quality of life of patients
      with high diabetes-related distress (DRD) in primary care. METHODS: A cross
      sectional, multicenter study was conducted in four primary healthcare
      institutions. Patients aged >= 21 years with T2DM were included; patients who
      were pregnant or unable to communicate independently were excluded from this
      study. The problem area in diabetes (PAID) measuring DRD, European quality of
      life-5 dimensions (EQ-5D), and audit of diabetes-dependent quality of life
      (ADDQoL) measuring quality of life were administered by trained research
      assistants. RESULTS: A total of 525 patients were eligible for this study. The
      mean PAID score was 26.90 +/- 20.23, with 27.8% of patients reporting having high
      DRD (PAID score >= 40). Patients who were younger than 50 years (OR 4.577, 95% CI
      1.977-10.600) and patients with HbA1c greater than 9% (OR 1.720, 95% CI 1.064
      2.779) were at higher risk of having high DRD (p < 0.05). Patients with high DRD
      have a lower EQ-5D index value (B = - 0.141) and ADDQoL AWI (B = - 1.276) than
      patients with little/no DRD (p < 0.001). CONCLUSION: High DRD was more common
      among younger patients and patients with poorer glycemic control. High DRD was
      associated with poorer quality of life and early screening and management of DRD
      is recommended.

PMID- 30194626
TI  - Health-related quality of life (HRQoL) in beta-thalassemia major (beta-TM)
      patients assessed by 36-item short form health survey (SF-36): a meta-analysis.
AB  - PURPOSE: The main purpose of this meta-analysis was to evaluate the impact of
      beta-thalassemia major (BTM) on the health-related quality of life as assessed by
      the medical outcomes short-form-36 questionnaire (SF-36). METHODS: A systematic
      literature search was performed on Cochrane library, Web of Science, Scopus,
      Science Direct, ProQues, Medline/PubMed, Scholar Google until March 17, 2017 to
      obtain eligible studies. A fixed effect model was applied to summarize the scores
      of each domain. The radar chart was used to compare the scores of BTM patients
      with other health conditions. Spearman's correlation analysis and meta-regression
      were used to explore the related factors. RESULTS: 26 studies were included in
      this study, which were all reliable to summarize the scores of the SF36. Pooled
      mean scores of the physical health domains ranged from 52.74 to 74.5, with the GH
      and PF domains being the lowest and the highest, respectively. Further, the
      pooled mean scores of the mental health domains varied between 59.6 and 71.11,
      with the (MH-VT) and SF domains being the maximum and the minimum, respectively.
      Patients with BTM had a substantially compromised HRQoL in comparison with the
      general population. CONCLUSION: BTM could adversely affect the HRQoL of patients.
      Measuring HRQoL should be considered as an essential part of the overall
      assessment of health status of BTM patients, which would provide valuable clues
      for improving the management of disease and making decisions on the treatment.

PMID- 30194627
TI  - Computational Study of HCV p7 Channel: Insight into a New Strategy for HCV
      Inhibitor Design.
AB  - HCV p7 protein is a cation-selective ion channel, playing an essential role
      during the life cycle of HCV viruses. To understand the cation-selective
      mechanism, we constructed a hexameric model in lipid bilayers of HCV p7 protein
      for HCB JFH-1 strain, genotype 2a. In this structural model, His9 and Val6 were
      key factors for the HCV cation-selective ion channel. The histidine residues at
      position 9 in the hexameric model formed a first gate for HCV p7 channel, acting
      as a selectivity filter for cations. The valines mentioned above formed a second
      gate for HCV p7 channel, serving as a hydrophobic filter for the dehydrated
      cations. The binding pocket for the channel blockers, e.g., amantadine and
      rimantadine, was composed of residues 20-26 in H2 helix and 52-60 in H3 helix in
      i + 2 monomer. However, the molecular volumes for both amantadine and rimantadine
      were too small for the binding pocket of HCV p7 channel. Thus, designing a
      compound similar with rimantadine and having much larger volume would be an
      effective strategy for discovering inhibitors against HCV p7 channel. To achieve
      this point, we used rimantadine as a structural template to search ChEMBL
      database for the candidates employing favorable binding affinities to HCV p7
      channel. As a result, six candidates were identified to have potential to be
      novel inhibitors against HCV p7 channel.

PMID- 30194628
TI  - An In-Silico Investigation of Key Lysine Residues and Their Selection for
      Clearing off Abeta and Holo-AbetaPP Through Ubiquitination.
AB  - Malicious progression of neurodegeneration is a consequence of toxic aggregates
      of proteins or peptides such as amyloid beta (Abeta) reported in Alzheimer's
      disease (AD). These aggregates hinder the electrochemical transmission at
      neuronal junctions and thus deteriorate neuronal-health by triggering dementia.
      Electrostatic and hydrophobic interactions among amino-acid residues are the
      governing principle behind the self-assembly of aforesaid noxious oligomers or
      agglomerate. Interestingly, lysine residues are crucial for these interactions
      and for facilitating the clearance of toxic metabolites through the
      ubiquitination process. The mechanisms behind lysine selectivity and
      modifications of target proteins are very intriguing process and an avenue to
      explore the clearance of unwanted proteins from neurons. Therefore, it is
      fascinating for the researchers to investigate the role of key lysine, their
      selectivity and interactions with other amino acids to clear-off toxic products
      in exempting the progression of Neurodegenerative disorders (NDDs). Herein, (1)
      we identified the aggregation prone sequence in Abeta40 and Abeta42 as
      'HHQKLVFFAE' and 'SGYEVHHQKLVFFAEDVG/KGAIIGLMVGGV' respectively with critical
      lysine (K) at 16 and 28 for stabilizing the aggregates; (2) elucidated the
      interaction pattern of AbetaPP with other Alzheimer's related proteins BACE1,
      APOE, SNCA, APBB1, CASP8, NAE1, ADAM10, and PSEN1 to describe the
      pathophysiology; (3) found APOE as commonly interacting factor between amyloid
      beta and Tau for governing AD pathogenesis; (4) reported K224, K351, K363, K377,
      K601, K662, K751, and K763 as potential putative lysine for facilitating AbetaPP
      clearance through ubiquitination thereby arresting Abeta formation; and (5)
      observed conserved glutamine (Q), glutamic acid (E), and alpha-helical
      conformation as few crucial factors for lysine selectivity in the ubiquitination
      of AbetaPP.

PMID- 30194629
TI  - Magnetically controlled growing rods for rigid scoliosis : An alternative to halo
      gravity traction in preparing for definitive correction?
AB  - The treatment concept for severe rigid idiopathic scoliosis is a short-term
      application of halo-gravity traction to enable maximum correction and subsequent
      dorsal fusion. The method has already been mentioned in the literature as an
      effective procedure. This case report demonstrates the use of a new treatment
      concept using magnetically controlled distraction rods as a possible alternative
      to the halo-gravity traction device. To our knowledge the use of this technique
      in severe rigid idiopathic scoliosis has not yet been published.

PMID- 30194630
TI  - A rare case of giant osteoblastoma of the sacrum.
AB  - BACKGROUND: An osteoblastoma is a rare benign bone tumor characterized by
      formation of osteoid tissue and primitive bone and occurs more often in men than
      in women. They are often secondary to an osteoid osteoma and can be located at
      any site on the skeleton. Lesions generally involve the posterior elements of the
      spine, such as the pedicle and the lamina. CASE PRESENTATION: This study reports
      the case of a 25-year-old female who suffered from an osteoblastoma of the right
      sacrum with repeated swelling and pain in the right lumbosacral region for
      approximately 6 months. Computed tomography (CT) and magnetic resonance imaging
      (MRI) of the pelvis revealed a segmented, expansive, multiseptate lesion.
      Resection with wide margins was performed and a huge cavity of approximately 15 *
      8 * 4.4 cm in the right sacrum and pelvis was formed after complete curettage of
      the tumor. The pathological analysis of the resected tissue was consistent with a
      benign osteoblastoma. A follow-up was performed 2 years later and the patient was
      eventually relieved of the pain, the mobility of the right leg was improved and
      the CT scan demonstrated no evidence of recurrence. CONCLUSION: Osteoblastomas
      most commonly occur in the spine but rarely also in the sacrum. Large core needle
      biopsies play an important role in the diagnostics. Intralesional surgery can be
      performed for treatment of osteoblastomas.

PMID- 30194631
TI  - [Bony contact in arthritic and healthy elbow joints : Studies in cadaveric
      specimens].
AB  - BACKGROUND: Arthroscopic and open debridement arthroplasty for elbow arthrosis
      produce excellent results. Resection of the tip of the olecranon and coronoid, as
      well as debridement of the associated fossae, is frequently described as
      sufficient for restoring range of motion and reducing pain. OBJECTIVES: The
      purpose of this study was to demonstrate that medial and lateral osteophytes of
      the olecranon and the coronoid usually mark the first bony contact and may,
      therefore, restrict range of motion. MATERIAL AND METHODS: 11 fresh-frozen elbows
      were dissected. The fossae were coated with Optosil P Plus (C-silicone), and
      maximal flexion and extension was simulated. The distribution of C-silicone
      impressions was documented. 6/7 donors were male. The mean age at the time of
      death was 82 . RESULTS: Out of 11 elbows, 4 exhibited arthritic changes. All
      arthritic elbows showed marginal osteophytes of the olecranon without
      characteristic dipping of the olecranon into its fossa. In 1/4 cases, additional
      osteophytes at the side of the coronoid were detected (in comparison to 1/7 in
      healthy elbows). CONCLUSION: The distribution of osteophytes in elbow arthrosis
      may be underestimated. Many clinicians describe a resection of the tip of the
      olecranon and the coronoid and debridement of the related fossa as sufficient.
      Our study supports the theory that marginal osteophytes, especially of the
      olecranon, should be resected during debridement arthroplasty, since the
      distribution of bony contact differs in arthritic and healthy elbows.

PMID- 30194632
TI  - Anterior cervical corpectomy and fusion : Spinal cord compression caused by
      buckled ligamentum flavum.
AB  - Anterior cervical corpectomy and fusion (ACCF) is a commonly performed surgical
      procedure for cervical spondylotic myelopathy (CSM). Various complications
      associated with ACCF have been reported; however, spinal cord compression caused
      by buckling of the ligamentum flavum (LF) after ACCF has not yet been well
      recognized. This article describes the case of a 59-year-old man who underwent
      ACCF at C5 for treatment of CSM. Although numbness and weakness of the upper
      extremities were relieved 2 weeks after the operation, gait imbalance persisted
      and worsened at 7 months. Magnetic resonance imaging (MRI) performed at 12 months
      revealed buckling of the LF into the spinal canal at the C5/6 level, compressing
      the spinal cord; moreover, high signal intensity in the spinal cord was observed
      beneath the buckling area on T2-weighted images. The secondary laminoplasty at C5
      and C6 was performed 13 months after primary surgery and MRI showed that the
      spinal canal was widened at the C5 and C6 levels and the spinal cord was
      decompressed.

PMID- 30194633
TI  - Palmitic acid induces human osteoblast-like Saos-2 cell apoptosis via endoplasmic
      reticulum stress and autophagy.
AB  - Palmitic acid (PA) is the most common saturated long-chain fatty acid in food
      that causes cell apoptosis. However, little is known about the molecular
      mechanisms of PA toxicity. In this study, we explore the effects of PA on
      proliferation and apoptosis in human osteoblast-like Saos-2 cells and uncover the
      signaling pathways involved in the process. Our study showed that endoplasmic
      reticulum (ER) stress and autophagy are involved in PA-induced Saos-2 cell
      apoptosis. We found that PA inhibited the viability of Saos-2 cells in a dose-
      and time-dependent manner. At the same time, PA induced the expression of ER
      stress marker genes (glucose-regulated protein 78 (GRP78) and CCAAT/enhancer
      binding protein homologous protein (CHOP)), altered autophagy-related gene
      expression (microtubule-associated protein 1 light chain 3 (LC3), ATG5, p62, and
      Beclin), promoted apoptosis-related gene expression (Caspase 3 and BAX), and
      affected autophagic flux. Inhibiting ER stress with 4-PBA diminished the PA
      induced cell apoptosis, activated autophagy, and increased the expression of
      Caspase 3 and BAX. Inhibiting autophagy with 3-MA attenuated the PA and ER stress
      induced cell apoptosis and the apoptosis-related gene expression (Caspase 3 and
      BAX), but seemed to have no obvious effects on ER stress, although the CHOP
      expression was downregulated. Taken together, our results suggest that PA-induced
      Saos-2 cell apoptosis is activated via ER stress and autophagy, and the
      activation of autophagy depends on the ER stress during this process.

PMID- 30194635
TI  - Interest of immunodeficiency screening in adult after admission in medical
      intensive care unit for severe infection, a retrospective and a prospective
      study: the Intensive Care Unit and Primary and Secondary Immunodeficiency
      (ICUSPID) study.
AB  - BACKGROUND: Primary immunodeficiency (PID) in adults is rare and mostly revealed
      by infections. MATERIAL AND METHODS: Adults without predisposing factors who were
      admitted to an intensive care unit (ICU) for infection were screened for PID.
      RESULTS: Six PID cases were diagnosed, mostly revealed by encapsulated bacterial
      infections. CONCLUSION: Investigation of PID after ICU discharge should be
      considered to improve early detection.

PMID- 30194634
TI  - Usefulness of TSH receptor antibodies as biomarkers for Graves' ophthalmopathy: a
      systematic review.
AB  - PURPOSE: Over the past several decades, many papers have been published about the
      usefulness of thyrotropin receptor antibodies (TRAbs) as biomarkers of Graves'
      ophthalmopathy (GO). However, results have been inconsistent. The purpose of this
      analysis is to determine a possible cause of these discrepancies and to examine
      the usefulness of TRAbs as biomarkers for GO, especially 'thyrotropin-binding
      inhibiting immunoglobulin (TBII)' and 'thyroid-stimulating antibody (TSAb)'.
      METHOD: 26 articles discussing the association between TRAbs and GO were selected
      which were then divided into three groups based on the study method and whether
      or not the patients had been treated for hyperthyroidism. From the results of the
      papers reviewed, a provisional conclusion was made and a theoretical model on the
      TBII-TSAb coordinate plane was developed to confirm that conclusion. RESULTS:
      TSAb is reported to be significantly or strongly associated with GO in the
      studies of pre- and post-treated patients for hyperthyroidism. TBII is positively
      correlated, negatively correlated or uncorrelated with GO in studies of pre
      treated patients. However, it is generally agreed upon that TBII and GO are
      closely correlated in studies of post-treated patients. CONCLUSION: We conclude
      that the level of TBII may not be a reliable indicator of the current state of GO
      in pre-treated patients. Whereas, in post-treated patients, due to changes in the
      correlation between TBII and TSAb due to the effect of hyperthyroidism treatment,
      the level of TBII can be a more reliable indicator of GO. Furthermore, the
      current level of TBII is closely associated with the onset and severity of GO in
      the future and it can be a valid predictor of GO. However, the TSAb level appears
      to be more reliable.

PMID- 30194636
TI  - Comparison of patient characteristics, clinical management, infectious specialist
      consultation, and outcome in men and women with methicillin-sensitive
      Staphylococcus aureus bacteremia: a propensity-score adjusted retrospective
      study.
AB  - BACKGROUND: Sex-related treatment inequalities are suggested to explain outcome
      differences between men and women in Staphylococcus aureus bacteremia (SAB). We
      compared patient characteristics, clinical management, infectious specialist
      consultation (ISC) and outcome in men and women with SAB. METHODS: Multicenter
      retrospective study of methicillin-sensitive (MS-) SAB patients categorized
      according to sex and ISC consultation provided within 7 days of diagnosis.
      RESULTS: Altogether 617 SAB patients were included in the analysis: 62% males and
      38% females. Male sex was associated less often to nosocomial bacteremia (OR
      0.69, 95% CI 0.50-0.96, p = 0.029) and more often to alcoholism (OR 2.25, 95% CI
      1.31-3.87, p = 0.003). No sex-related differences were seen in basic or
      immunologic laboratory tests, illness severity, intensive care unit treatment or
      thromboembolic events. ISC was provided to most patients (94%) irrespective of
      sex. No differences were seen in clinical management of men or women:
      Transthoracic or -esophageal echocardiography (61% vs. 65%), deep infection (77%
      vs. 72%), infection removal (30% vs. 27%) and anti-staphylococcal antibiotics as
      first-line treatment (54% vs. 51%). However, male sex was connected to more
      frequent adjunctive rifampicin treatment (52% vs. 41%, p = 0.025). No difference
      in 28- or 90-day mortality (13% vs. 13% and 18% vs. 20%) or SAB relapse (0% vs.
      1%) was observed between men and women. Propensity-score adjusted Cox
      proportional analysis gave no connection of sex to mortality within 90 days.
      CONCLUSION: Patient characteristics, clinical management, ISC guidance,
      bacteremia relapse, and outcome did not differ in men and women with MS-SAB.

PMID- 30194637
TI  - The diagnostic challenge in very-long chain acyl-CoA dehydrogenase deficiency
      (VLCADD).
AB  - Very long-chain acyl-CoA dehydrogenase deficiency (VLCADD) is the most common
      defect of mitochondrial beta-oxidation of long-chain fatty acids. However, the
      unambiguous diagnosis of true VLCADD patients may be challenging, and a high rate
      of false positive individuals identified by newborn screening undergo
      confirmation diagnostics. In this study, we show the outcome of enzyme testing in
      lymphocytes as a confirmatory tool in newborns identified by screening, and the
      correlation with molecular sequencing of the ACADVL gene. From April 2013 to
      March 2017, in 403 individuals with characteristic acylcarnitine profiles
      indicative of VLCADD, palmitoyl-CoA oxidation was measured followed by molecular
      genetic analysis in most of the patients with residual activity (RA) <50%. In
      almost 50% of the samples (209/403) the RA was >50%, one-third of the individuals
      (125/403) displayed a RA of 30-50% and 69/403 individuals showed a residual
      activity of 0-30%. Sequencing of the ACADVL gene revealed that all individuals
      with activities below 24% were true VLCADD patients, individuals with residual
      activities between 24 and 27% carried either one or two mutations. Twenty new
      mutations could be identified and functionally classified based on their effect
      on enzyme function. Finally, we observed an up-regulation of MCAD-activity in
      many patients. However, this did not correlate with the degree of VLCAD RA.
      Although the likely clinical phenotype cannot be fully foreseen by genetic and
      functional tests as it depends on many factors, our data demonstrate the strength
      of this functional enzyme test in lymphocytes as a quick and reliable method for
      confirmation diagnostics of VLCADD.

PMID- 30194639
TI  - [Typical fractures and dislocations of the elbow joint and their treatment].
AB  - Diagnosis and treatment of injuries to the elbow joint place high demands on the
      treating physicians. The complex anatomy of the elbow joint enables a wide range
      of movement and complex functions in everyday and professional life. These must
      be restored in the event of injury.Clinical and imaging-based diagnostic
      procedures serve to classify typical injuries of this joint according to a large
      variety of different pathologies. These include fractures of the distal humerus,
      the proximal ulna, and the radial head, as well as dislocations and dislocation
      fractures.The following article gives an overview of the most common of these
      injuries.

PMID- 30194640
TI  - [Nuclear magnetic resonance: The explorers].

PMID- 30194641
TI  - [Soft-tissue and bone debridement].

PMID- 30194638
TI  - Potential therapeutic value of transient receptor potential channels in male
      urogenital system.
AB  - Transient receptor potential (TRP) channels comprise a family of cation channels
      implicated in a variety of cellular processes including light, mechanical or
      chemical stimuli, temperature, pH, or osmolarity. TRP channel proteins are a
      diverse family of proteins that are expressed in many tissues. We debated our
      recent knowledge about the expression, function, and regulation of TRP channels
      in the different parts of the male urogenital system in health and disease.
      Emerging evidence suggests that dysfunction of TRP channels significantly
      contributes to the pathophysiology of urogenital diseases. So far, there are many
      efforts underway to determine if these channels can be used as drug targets to
      reverse declines in male urogenital function. Furthermore, developing safe and
      efficacious TRP channel modulators is warranted for male urogenital disorders in
      a clinical setting.

PMID- 30194642
TI  - [Modified Salter innominate osteotomy in adults].
AB  - OBJECTIVE: The dysplastic acetabulum is shifted three-dimensionally outwards and
      forwards. INDICATIONS: Symptomatic residual hip dysplasias and hip subluxations
      in skeletally mature patients up to the age of 50 years. Sharp's acetabular up to
      60 degrees , as an exception above 60 degrees . CONTRAINDICATIONS: Acetabular
      retroversion. Radiographic joint space at the lateral acetabular edge that is
      less than half the normal thickness for the patient's age. Relative
      contraindication: Elongated leg on the affected side. SURGICAL TECHNIQUE:
      Ilioinguinal approach in a supine position. Division of the innominate bone.
      Pivoting the distal osteotomy fragment outwards and forwards with the aid of the
      Salter maneuver. Fixing the fragments with a guide wire. Final correction of the
      osteotomy fragments. Force fitting of a dovetail grooved, wedge-shaped bone
      graft. Insertion of a cannulated compression screw and two further threaded rods.
      Wound closure. POSTOPERATIVE MANAGEMENT: Unloaded 3-point walking for 4 weeks.
      Increasing weight bearing from week 4. Full weight bearing from week 10-12.
      RESULTS: A total of 45 consecutive patients (7 men, 38 women, 49 hips) underwent
      surgery. Average age at surgery was 27.6 years. The Sharp acetabular angle
      improved from preoperatively 45.7 degrees  +/- 4.2 degrees  by 13.8 degrees  to
      32.0 degrees  +/- 6.4 degrees ; the Wiberg (LCE) angle increased from 15.4
      degrees  +/- 9.3 degrees  by 19.5 degrees  to 34.9 degrees  +/- 10 degrees 
      postoperatively. The anterior center edge (ACE) angle increased from 28.9 degrees
      +/- 10.4 degrees  by 8.6 degrees  +/- 2.3 degrees  to 37.5 degrees  +/- 8.1
      degrees . Complications requiring surgical intervention occurred in 7 patients.

PMID- 30194643
TI  - Development of a technical checklist for the assessment of suturing in robotic
      surgery.
AB  - BACKGROUND: With the increased use of simulation for surgical training, there is
      a need for objective forms of assessment to evaluate trainees. The Global
      Evaluative Assessment of Robotic Skills (GEARS) is widely used for assessing
      skills in robotic surgery, but there are no recognised checklist scoring systems.
      This study aimed to develop a checklist for suturing in robotic surgery. METHODS:
      A suturing checklist for needle driving and knot tying was constructed following
      evaluation of participants performing urethrovesical anastomoses. Key procedural
      steps were identified from expert videos, while assessing novice videos allowed
      identification of common technical errors. 22 novice and 13 expert videos were
      marked on needle driving, while 18 novices and 10 experts were assessed on knot
      tying. Validation of the finalised checklist was performed with the assessment of
      39 separate novices by an expert surgeon and compared to GEARS scoring. RESULTS:
      The internal consistency of the preliminary checklist was high (Cronbach's alpha
      = 0.870 for needle driving items; 0.736 for knot tying items), and after removal
      of poorly correlating items, the final checklist contained 23 steps. Both the
      needle driving and knot tying categories discriminated between novices and
      experts, p < 0.005. While the GEARS score demonstrated construct validity for
      needle driving, it could not significantly differentiate between novices and
      experts for knot tying, p = 0.286. The needle driving category significantly
      correlated with the corresponding GEARS scores (rs = 0.613, p < 0.005), but the
      correlation for knot tying was insignificant (rs = 0.296, p = 0.127). The pilot
      data indicates the checklist significantly correlated with the GEARS score (p <
      0.005). CONCLUSION: This study reports the development of a valid assessment tool
      for suturing in robotic surgery. Given that checklists are simple to use, there
      is significant scope for this checklist to be used in surgical training.

PMID- 30194644
TI  - One or two trainees per workplace for laparoscopic surgery training courses:
      results from a randomized controlled trial.
AB  - BACKGROUND: There are no standards for optimal utilization of workplaces in
      laparoscopic training. This study aimed to define whether laparoscopy training
      should be done alone or in pairs (known as dyad training). METHODS: This was a
      three-arm randomized controlled trial with laparoscopically naive medical
      students (n = 100). Intervention groups participated alone (n = 40) or as dyad (n
      = 40) in a multimodality training curriculum with e-learning, basic, and
      procedural skills training using box and VR trainers. The control group (n = 20)
      had no training. Post-performance of a cadaveric porcine laparoscopic
      cholecystectomy (LC) was measured as the primary outcome by blinded raters using
      the objective structured assessment of technical skills (OSATS). Global operative
      assessment of laparoscopic skills (GOALS), time for LC, and VR performances were
      secondary outcomes. RESULTS: There were no differences between groups for
      performance scores [OSATS: alone (40.2 +/- 9.8) vs. dyad (39.8 +/- 8.6), p =
      0.995; alone vs. control (37.1 +/- 7.4), p = 0.548; or dyad vs. control, p =
      0.590; and GOALS score: alone (10.6 +/- 3.0) vs. dyad (10.0 +/- 2.7), p = 0.599;
      alone vs. control (10.1 +/- 3.0), p = 0.748; or dyad vs. control, p = 0.998].
      Dyad finished LC faster than control [median = 62.5 min (CI 58.0-73.0) vs. 76.5
      min (CI 72.0-80+); p = 0.042], while there were no inter-group differences
      between alone vs. control [median = 69.0 min (CI 62.0-76.0) vs. control; p =
      0.099] or alone vs. dyad (p = 0.840). Dyad and alone showed superior performance
      on the VR trainer vs. control for time, number of movements, and path length, but
      not for complications and application of cautery. CONCLUSIONS: The curriculum
      provided trainees with the laparoscopic skills needed to perform LC safely,
      irrespective of the number of trainees per workplace. Dyad training reduced the
      operation time needed for LC. Therefore, dyad training seems to be a promising
      alternative, especially if training time is limited and resources must be used as
      efficiently as possible. Trial registration German Clinical Trials Register:
      DRKS00004675.

PMID- 30194645
TI  - Laparoscopic lateral pancreaticojejunostomy: an evolution to endostapled
      technique.
AB  - BACKGROUND: Chronic pancreatitis (CP) is a debilitating condition resulting in
      severe pain with progressive deterioration of pancreatic function. "Tropical"
      pancreatitis represents a variant of the disease with widely dilated ducts,
      numerous calculi, and few strictures. Traditionally, modified Puestow's procedure
      has been the treatment of choice for a dilated pancreatic ductal system. However,
      it has only recently been adapted to laparoscopic approach which is a technically
      demanding procedure primarily due to need for extensive intra-corporeal suturing.
      METHODS: Symptomatic cases of CP presenting at our center with minimum 8 mm mean
      ductal diameter at body and head were selected for laparoscopic modified
      Puestow's procedure. Those with prior pancreatic surgery, pancreatic head masses,
      endoscopic pancreatic stenting, and portal hypertension were excluded. Twenty
      eight cases meeting selection criteria underwent a laparoscopic procedure.
      RESULTS: Seven patients (25%) underwent a stapled pancreaticojejunal anastomosis,
      17 (60.7%) received a sutured anastomosis. Four patients (14.3%) were converted
      to open surgery due to failure to localize the pancreatic duct with percutaneous
      needle aspiration. Of those patients who underwent a successful laparoscopic
      procedure, a single patient developed a pancreatic fistula which resolved
      spontaneously; another patient had a difficult post-operative course with
      prolonged intensive care. We suffered no mortality within the series and no
      patient had any long-term disability. Anastomotic patency rates of 100% were
      achieved by the third post-operative month. CONCLUSION: Lateral
      pancreaticojejunostomy is an effective surgical management for CP with a dilated
      ductal system. Its laparoscopic adoption is the rational next surgical step. It
      allows effective duct decompression with low mortality and morbidity. The
      procedure demands an advanced surgical skill set with an emphasis on intra
      corporeal suturing. Those patients suffering from tropical CP with wide ductal
      dilatation greater than 12 mm are suited to an endostapled anastomosis which
      helps significantly reduce operative time without any corrosion of outcomes.

PMID- 30194646
TI  - Macrophages but not Astrocytes Harbor HIV DNA in the Brains of HIV-1-Infected
      Aviremic Individuals on Suppressive Antiretroviral Therapy.
AB  - The question of whether the human brain is an anatomical site of persistent HIV-1
      infection during suppressive antiretroviral therapy (ART) is critical, but
      remains unanswered. The presence of virus in the brains of HIV patients whose
      viral load is effectively suppressed would demonstrate not only the potential for
      CNS to act as an anatomical HIV reservoir, but also the urgent need to understand
      the factors contributing to persistent HIV behind the blood-brain barrier. Here,
      we investigated for the first time the presence of cells harboring HIV DNA and
      RNA in the brains from subjects with undetectable plasma viral load and sustained
      viral suppression, as identified by the National NeuroAIDS Tissue Consortium.
      Using new, highly sensitive in situ hybridization techniques, RNAscope and
      DNAscope, in combination with immunohistochemistry, we were able to detect HIV-1
      in the brains of all virally suppressed cases and found that brain macrophages
      and microglia, but not astrocytes, were the cells harboring HIV DNA in the brain.
      This study demonstrated that HIV reservoirs persist in brain
      macrophages/microglia during suppressive ART, which cure/treatment strategies
      will need to focus on targeting.

PMID- 30194647
TI  - Infant skull fracture risk for low height falls.
AB  - Skull fractures are common injuries in young children, typically caused by
      accidental falls and child abuse. The paucity of detailed biomechanical data from
      real-world trauma in children has hampered development of biomechanical
      thresholds for skull fracture in infants. The objectives of this study were to
      identify biomechanical metrics to predict skull fracture, determine threshold
      values associated with fracture, and develop skull fracture risk curves for low
      height falls in infants. To achieve these objectives, we utilized an integrated
      approach consisting of case evaluation, anthropomorphic reconstruction, and
      finite element simulation. Four biomechanical candidates for predicting skull
      fracture were identified (first principal stress, first principal strain, shear
      stress, and von Mises stress) and evaluated against well-witnessed falls in
      infants (0-6 months). Among the predictor candidates, first principal stress and
      strain correlated best with the occurrence of parietal skull fracture. The
      principal stress and strain thresholds associated with 50 and 95% probability of
      parietal skull fracture were 25.229 and 36.015 MPa and 0.0464 and 0.0699,
      respectively. Risk curves using these predictors determined that infant falls
      from 0.3 m had a low probability (0-54%) to result in parietal skull fracture,
      particularly with carpet impact (0-1%). Head-first falls from 0.9 m had a high
      probability of fracture (86-100%) for concrete impact and a moderate probability
      (34-81%) for carpet impact. Probabilities of fracture in 0.6 m falls were
      dependent on impact surface. Occipital impacts from 0.9 m onto the concrete also
      had the potential (27-90% probability) to generate parietal skull fracture. These
      data represent a multi-faceted biomechanical assessment of infant skull fracture
      risk and can assist in the differential diagnosis for head trauma in children.

PMID- 30194648
TI  - Astrocytic degeneration in chronic traumatic encephalopathy.
AB  - Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated
      with repeated head traumas. Using immunohistochemistry for glial fibrillary
      acidic protein as a marker, plus automated quantitative analysis, we examined the
      characteristics and extent of astrogliosis present in stage III and IV CTE, along
      with Alzheimer's disease (AD), and frontotemporal dementia (FTD) cases.
      Astrogliosis in CTE patients was more diffuse compared to that of AD and FTD
      patients, which was concentrated in the sulcal depths. Of 14 patients with CTE,
      10 exhibited signs of a degenerating astrocyte pathology, characterized by
      beaded, broken astrocytic processes. This astrocytic degeneration was typically
      found to be diffuse throughout the white matter, although two cases demonstrated
      astrocytic degeneration in the gray matter. The degeneration was also observed in
      2 of 3 AD and 2 of 3 FTD brains, with overall similar characteristics across
      diseases. There was minimal to no astrocytic degeneration in six age-matched
      controls with no neurodegenerative disease. We found that the extent of the white
      matter astrocytic degeneration was strongly correlated with the level of overall
      astrogliosis in both the white and gray matter. However, astrocytic degeneration
      was not correlated with the overall extent of tau pathology. Specifically, there
      was no correlation between levels of p-tau in the sulcal depths and astrocytic
      degeneration in the white matter adjacent to the sulcal depths. Thus, astrocytic
      degeneration and overall astrogliosis appear to represent distinct pathological
      features of CTE. Further investigation into these astroglial pathologies could
      provide new insights into underlying disease mechanisms and represent a potential
      target for in vivo assessment of CTE as well as other neurodegenerative
      disorders.

PMID- 30194649
TI  - Prolonged remission is associated with a reduced risk of cardiovascular disease
      in patients with systemic lupus erythematosus: a GIRRCS (Gruppo Italiano di
      Ricerca in Reumatologia Clinica e Sperimentale) study.
AB  - Prolonged remission (PR), defined as a 5-year consecutive period of no disease
      activity based on SLEDAI-2K, has been reported to be associated with a lower
      damage accrual over time in patients with systemic lupus erythematosus (SLE), as
      the consequence of a lower activity burden. Since disease activity is considered
      to play a role in the incidence of cardiovascular disease (CVD), we investigated
      the relationship, if any, between PR and the occurrence of a subsequent first CV
      event in patients with SLE. Out of 488 patients consecutively admitted to two
      tertiary Italian centers from November 1, 2000, to December 31, 2016, the 294
      patients, who had been followed at least for 5 years, had not experienced any CV
      event at admission, and had been visited biannually during follow-up, were
      considered for the present study. The incidence of a first CV in patients who had
      achieved PR was compared with that registered in those who had not. Moreover, it
      was compared among PR patients subdivided into three groups: complete remission,
      clinical off-corticosteroids (offCR), and clinical on-corticosteroids remission
      (onCR). Kaplan-Meier curves and the log-rank test were used to analyze
      differences in event-free survival among groups. Cox regression was used to
      investigate disease and therapeutic features associated with the development of a
      first CV event. During 9 years median follow-up time, 24 (8.1%) CV events
      occurred. Out of the 294 patients, 126 (42.8%) had achieved PR. Kaplan-Meier
      analysis revealed a greater overall CV event-free rate in these patients as
      compared to both those with a shorter lasting remission and those who had never
      remitted (log-rank test chi2 = 14.43; p = 0.0001). In addition, CV outcome did
      not differ among PR patients, irrespectively the type of remission achieved (p >
      0.05). At multivariate analysis, hydroxychloroquine therapy and PR resulted to be
      protective (HR 0.19; HR 0.18), while arterial hypertension and antiphospholipid
      positivity increased the risk of a first CV event (HR 2.61; HR 2.47). The PR,
      whichever the subtype, is associated with a better CV outcome and should be
      considered as a treat-to-target goal in the CV risk management of the lupus
      patient.

PMID- 30194650
TI  - Medication Exposure and Health Outcomes in Older Patients with End-Stage Kidney
      Disease: A Prospective Study Undertaken in New Zealand.
AB  - BACKGROUND: The impact of multiple medication exposure on health outcomes among
      older patients with end-stage kidney disease (ESKD) is unknown. OBJECTIVE: The
      objective of this study was to identify the impact of medicine exposure on
      hospitalisation rates and mortality in a prospective longitudinal observational
      study of older dialysis patients. METHODS: Patient demographics, medication use,
      hospitalisation, mortality and co-morbidity data were collected through the
      prospective longitudinal cohort study DOS65 + (Dialysis Outcomes in those aged >=
      65 years Study) (n = 225). Medication exposure was measured by the total number
      of individual medications and the number of predetermined 'medication groups'.
      Associations between medications prescribed at recruitment and health outcomes as
      measured by hospitalisation and mortality were assessed by univariate and
      multivariable regression analyses. RESULTS: Older ESKD patients were exposed to a
      median of ten (0-20) medications and eight (0-15) medication groups. Multivariate
      analyses estimate each additional medication increased mortality risk by 8%
      (relative risk [RR] = 1.08; 95% confidence interval [CI] 1.07-1.09); each
      medication group increased mortality risk by 11% (RR = 1.11; 95% CI 1.09-1.12).
      Similar trends were observed for hospitalisation. Certain medication groups were
      associated with reduced hospitalisation rates, namely angiotensin converting
      enzyme (ACE) inhibitors/angiotensin receptor blockers (RR = 0.62; 95% CI 0.53
      0.72) and dihydropyridines (RR = 0.64; 95% CI 0.54-0.76). Warfarin, gastric acid
      suppressants, diuretics and beta-blockers were associated with increased
      hospitalisation rates. Warfarin was associated with an increased mortality rate
      (RR = 1.40; 95% CI 1.19-1.65). CONCLUSIONS: Multiple medication exposure was
      prevalent in this older ESKD population, and was associated with an increased
      risk of mortality and hospitalisation. While this study is not able to determine
      the cause of these relationships, review of medication use is warranted in this
      population. TRIAL REGISTRATION: ACTRN12611000024943.

PMID- 30194651
TI  - Defining growth potential and barriers to same day discharge total knee
      arthroplasty.
AB  - BACKGROUND: Outpatient arthroplasty programs are becoming well established.
      Adverse event rates have been demonstrated to be no worse than inpatient
      arthroplasty in the literature for selected patients. The purpose of this study
      was to determine our rate of outpatient total knee arthroplasty (TKA), examine
      justification for exclusions, and estimate the proportion of TKAs that can occur
      safely on an outpatient basis. METHODS: Retrospective case series of 400
      consecutive TKAs from Oct 2014 to Mar 2017. Patient demographics, allocation to
      outpatient surgery vs standard admission, and reason for exclusion from
      outpatient surgery were recorded. Ninety-day Emergency department (ED) visits,
      readmission rates, and length of stay (LOS) were compared between groups using
      independent sample t test and Chi-squared test. RESULTS: Outpatients were younger
      (p = 0.001), had lower BMI (p < 0.001), and ASA scores (p < 0.001) than
      inpatients. One hundred twenty-five (31%) TKAs were assigned to outpatient
      surgery and 123 achieved discharge on the same day. There was no difference in 90
      day ED visits (p = 0.889) or readmission rates (p = 0.338) between groups.
      Reasons for exclusion from outpatient surgery included medical (absolute 43% and
      relative 31%), distance > one hour from hospital (18%), no help (7%), and
      other/unclear (10%). LOS was significantly longer for medical than non-medical
      exclusions (p < 0.001) and for the absolute compared to relative medical
      exclusions (p = 0.004). CONCLUSION: Outpatient TKA is safe in selected patients,
      and inclusion can likely be broadened by addressing modifiable exclusions and
      narrowing medical exclusions. We found that 55% of our TKA population could be
      appropriate for outpatient surgery.

PMID- 30194652
TI  - Revision of ASR hip arthroplasty: analysis of two hundred and ninety six recalled
      patients at seven years.
AB  - PURPOSE: The aim of this study is to present an algorithm for the evaluation of
      both symptomatic and asymptomatic patients. METHODS: From November 2004 to May
      2010, there were performed 296 operations: 245 total hip arthroplasty and 51
      resurfacing arthroplasty with the ASR DePuy system. In April 2010, there was the
      first Medical Device Alert regarding all MoM hip replacements in the UK and in
      August 2010, DePuy recall started worldwide. In March 2012, we started our
      recall. All patients were invited to undergo clinical investigation, X-ray
      evaluations, and blood chrome and cobalt level determination. For a short period
      of time, there were performed second level exams and subsequently, we carried out
      MARS MRI hip study to all symptomatic patients and there was evidence of ALVAL
      lesions. RESULTS: To the patients with ALVAL lesions were proposed surgical hip
      revision while the others frequent follow-up controls. One hundred patients
      underwent hip surgical revision. CONCLUSIONS: We recommend constant MoM THA
      patients monitoring and early revision if necessary.

PMID- 30194653
TI  - Population development of the predatory mite Amblydromalus limonicus is modulated
      by habitat dispersion, diet and density of conspecifics.
AB  - Habitat dispersion, diet and density can influence the per capita population
      growth of predators, and dispersed habitat can provide a spatial refuge that
      reduces the possibility of cannibalism among predators, thereby increasing their
      realized population growth rate. We tested the influence of variable habitat
      dispersion (dispersed patches, general patches and aggregated patches), two diets
      (Typha orientalis pollen and Ephestia kuehniella eggs) and initial predator
      density-one or two Amblydromalus limonicus (Garman and McGregor) (Acari:
      Phytoseiidae) founder females-on the population growth of A. limonicus in 7 days.
      Dispersed patches resulted in a higher total number of A. limonicus than the
      other two types of habitat dispersion from days 3-7 when fed on either of the
      diets, and started with either one or two A. limonicus females. Compared with E.
      kuehniella eggs, T. orientalis pollen resulted in more A. limonicus regardless of
      one or two founder females. Compared with two founder females, beginning with one
      founder female on pollen produced significantly more predatory mite females in
      dispersed and aggregated patches. A four-way ANOVA showed that the main effects
      indicated that habitat, diet, density, and time significantly influenced the
      number of immature and female A. limonicus. Significant interactions between
      habitat dispersion and diet were detected on immature and female A. limonicus.
      Our findings suggest that increasing the dispersion of artificial shelters on
      crop leaves may stimulate the control efficiency of predators in greenhouses.
      Furthermore, T. orientalis pollen provides a high nutritional quality
      supplemental diet that could enhance the ability of A. limonicus to control
      pests.

PMID- 30194655
TI  - Proportional cross-ratio model.
AB  - Cross-ratio is an important local measure of the strength of dependence among
      correlated failure times. If a covariate is available, it may be of scientific
      interest to understand how the cross-ratio varies with the covariate as well as
      time components. Motivated by the Tremin study, where the dependence between age
      at a marker event reflecting early lengthening of menstrual cycles and age at
      menopause may be affected by age at menarche, we propose a proportional cross
      ratio model through a baseline cross-ratio function and a multiplicative
      covariate effect. Assuming a parametric model for the baseline cross-ratio, we
      generalize the pseudo-partial likelihood approach of Hu et al. (Biometrika 98:341
      354, 2011) to the joint estimation of the baseline cross-ratio and the covariate
      effect. We show that the proposed parameter estimator is consistent and
      asymptotically normal. The performance of the proposed technique in finite
      samples is examined using simulation studies. In addition, the proposed method is
      applied to the Tremin study for the dependence between age at a marker event and
      age at menopause adjusting for age at menarche. The method is also applied to the
      Australian twin data for the estimation of zygosity effect on cross-ratio for age
      at appendicitis between twin pairs.

PMID- 30194654
TI  - Correction to: A Versatile Vector Toolkit for Functional Analysis of Rice Genes.
AB  - The caption of Fig. 5 and the figure contained an error [1]. The updated figure
      and caption are published in this correction article.

PMID- 30194656
TI  - Geraniin promotes osteogenic differentiation of bone marrow mesenchymal stem
      cells (BMSCs) via activating beta-catenin: a comparative study between BMSCs from
      normal and osteoporotic rats.
AB  - Abnormal osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs)
      has been correlated with the pathogenesis of osteoporosis. Geraniin, a
      polyphenolic compound isolated from Phyllanthus amarus, is effective in
      preventing osteoporosis, but the mechanisms of action of geraniin and the impact
      of osteoporotic condition on drug action are not known. In this study we compared
      the proliferation and osteoblastic differentiation potential of BMSCs from normal
      rats with that from osteoporotic rats, and examined the responses of both BMSCs
      to geraniin in parallel. BMSCs of rats subjected to ovariectomy or sham operation
      were isolated and treated with geraniin. Cell proliferation was measured by CCK-8
      assay. Osteoblastic differentiation was quantified by Alizarin Red S staining and
      alkaline phosphatase assay. Nuclear translocation of beta-catenin was monitored
      by immunofluorescent staining. Expression of beta-catenin was determined by
      Western blot and quantitative real-time polymerase chain reaction. Results showed
      that the proliferation and osteoblast formation of osteoporotic BMSCs decreased
      in comparison to that of normal BMSCs. Geraniin enhanced proliferation and
      osteoblastic differentiation of both BMSCs, but the responses of osteoporotic
      BMSCs to geraniin were less than those of normal BMSCs. Expression and nuclear
      accumulation of beta-catenin in osteoporotic BMSCs were found to be diminished.
      Geraniin increased nuclear translocation and expression of beta-catenin in both
      BMSCs. This study associated the osteogenic effect of geraniin to activation of
      Wnt/beta-catenin signaling, and provided rationale for pharmacological
      investigation of geraniin in osteoporosis prevention and treatment.

PMID- 30194657
TI  - Ameliorative effect of Xiaoyao-jieyu-san on post-stroke depression and its
      potential mechanisms.
AB  - A stroke is a severe life-threatening disease with high fatality and disability
      rate. This investigation aimed to study the effect of Xiaoyao-jieyu-san (XYJY) on
      post-stroke depression (PSD) and its potential mechanisms. PSD rats were prepared
      using middle cerebral artery embolization (MCAO) and chronic unpredictable mild
      stress (CUMS), and divided into six groups (n = 10)-sham; MCAO; MCAO + CUMS
      (PSD); PSD + fluoxetine (1.84 mg/kg/day, 4 weeks); and PSD + XYJY (450 mg/kg/day
      and 900 mg/kg/day, 4 weeks). Body weight recording, despair swimming test, and
      sucrose preference test were performed at 0, 3 and 7 weeks. Histopathological
      examination and levels of 5-hydroxytryptamine (5-HT), norepinephrine (NE) and
      brain-derived neurotrophic factor (BDNF) in ventral tegmental area-nucleus
      accumbens (VTA-NAc) tissue were determined at the end of a 7-week period. Real
      time polymerase chain reaction PCR was used to determine mRNA expression of 5
      HT1AR and 5-HT2AR, and Western blot was performed to determine expression of
      BDNF, corticotrophin-releasing factor (CRF), and cannabinoid receptors (CB1R and
      CB2R) in VTA-NAc tissue. High-performance liquid chromatography coupled with
      electrospray mass spectroscopy revealed that the constituents of XYJY are mainly
      paeoniflorin, imperatorin, naringin, arnesene, 2,3,5,4'-tetrahydroxyl
      diphenylethylene-2-O-glucoside, kaempferol-3-O-rutinoside, quercetin, hesperidin,
      cycloastragenol and atractylenolide III. XYJY (900 mg/kg) increased the body
      weight of PSD rats, while XYJY (450 mg/kg and 900 mg/kg) shortened the duration
      of immobility and enhanced the sucrose preference of PSD rats. XYJY (450 mg/kg
      and 900 mg/kg) increased the levels of 5-HT, NE and BNDF, up-regulated mRNA
      expression of 5-HT1AR, down-regulated 5-HT2AR, and up-regulated BNDF, CB1R, and
      CB2R expression in the VTA-NAc tissue of PSD rats but down-regulated CRF.
      Collectively, the present findings suggested that XYJY has an ameliorative effect
      on PSD in rats via modulation of BNDF, cannabinoid receptors and CRF in VTA-NAc
      tissue.

PMID- 30194659
TI  - Gap Junctions and Wnt Signaling in the Mammary Gland: a Cross-Talk?
AB  - Connexins (Cxs), the building blocks of gap junctions (GJs), exhibit
      spatiotemporal patterns of expression and regulate the development and
      differentiation of the mammary gland, acting via channel-dependent and channel
      independent mechanisms. Impaired Cx expression and localization are reported in
      breast cancer, suggesting a tumor suppressive role for Cxs. The signaling events
      that mediate the role of GJs in the development and tumorigenesis of the mammary
      gland remain poorly identified. The Wnt pathways, encompassing the canonical or
      the Wnt/beta-catenin pathway and the noncanonical beta-catenin-independent
      pathway, also play important roles in those processes. Indeed, aberrant Wnt
      signaling is associated with breast cancer. Despite the coincident roles of Cxs
      and Wnt pathways, the cross-talk in the breast tissue is poorly defined, although
      this is reported in a number of other tissues. Our previous studies revealed a
      channel-independent role for Cx43 in inducing differentiation or suppressing
      tumorigenesis of mammary epithelial cells by acting as a negative regulator of
      the Wnt/beta-catenin pathway. Here, we provide a brief overview of mammary gland
      development, with emphasis on the role of Cxs in development and tumorigenesis of
      this tissue. We also discuss the role of Wnt signaling in similar contexts, and
      review the literature illustrating interplay between Cxs and Wnt pathways.

PMID- 30194660
TI  - Review: the Role and Mechanisms of Macrophage Autophagy in Sepsis.
AB  - Sepsis is a systemic inflammatory response syndrome caused by infection. The core
      mechanism underlying sepsis is immune dysfunction, with macrophages, as important
      cells of the innate immune system, playing an essential role. Autophagy has been
      shown to be closely related to inflammation and immunity, and autophagy
      enhancement in sepsis can play a protective role by negatively regulating
      abnormal macrophage activation, modulating macrophage polarization phenotype,
      reducing activation of the inflammasome and release of inflammatory factors, and
      affecting macrophage apoptosis. However, excessive autophagy may also lead to
      autophagic death of macrophages, which further aggravates the inflammatory
      response. The mechanisms underlying these functions are relatively complex and
      remain unclear, but may be related to a variety of signaling pathways such as NF
      kappaB, mTOR, and PI3K/AKT. The administration of drugs to assist in the
      regulation of macrophage autophagy has become a novel treatment for sepsis. The
      present review focuses on the role and the potential mechanisms of macrophage
      autophagy in sepsis.

PMID- 30194661
TI  - Elagolix: First Global Approval.
AB  - Elagolix (ORILISSATM), an orally bioavailable, second-generation, non-peptide
      gonadotropin-releasing hormone (GnRH) receptor antagonist, is being developed
      AbbVie and Neurocrine Biosciences for the treatment of reproductive hormone
      dependent disorders in women. In July 2018, the US FDA approved elagolix tablets
      for the management of moderate to severe pain associated with endometriosis. This
      approval was based on positive results in two replicate phase III trials;
      additional phase III trials in the USA, Canada and Puerto Rico are currently
      evaluating elagolix as both monotherapy and in combination with low-dose hormone
      add-back therapy in the same indication. Elagolix with and without low-dose
      hormone add-back therapy is also undergoing phase III clinical development for
      heavy menstrual bleeding associated with uterine fibroids in the aforementioned
      locations. This article summarizes the milestones in the development of elagolix
      leading to its first approval for the management of moderate to severe pain
      associated with endometriosis.

PMID- 30194662
TI  - Evaluation of health-related quality of life via the Computer-Based Health
      Evaluation System (CHES) for Japanese metastatic breast cancer patients: a single
      center pilot study.
AB  - BACKGROUND: The main purposes of metastatic breast cancer (MBC) treatment are to
      prolong survival and maintain health-related quality of life (HRQOL). Compliance
      with the HRQOL assessment can be poor, particularly among patients who receive
      long-term treatment. One possible solution to overcoming this problem is to
      engage in real-time home monitoring by having patients report outcomes on their
      personal electronic devices. The objective of this study was to investigate
      compliance with HRQOL monitoring from home among MBC patients using the Computer
      Based Health Evaluation System (CHES) to collect patient data. METHODS: Sixteen
      MBC patients who received outpatient chemotherapy or endocrine therapy, both with
      and without targeted therapy, were recruited. One eligibility criterion was the
      availability of a personal electronic device with access to the Internet.
      Patients were asked to enter HRQOL ratings from their personal electronic devices
      via CHES once every week for 12 weeks. The European Organization for Research and
      Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ C30) was
      used to evaluate HRQOL. The outcome examined was the questionnaire collection
      rate. RESULTS: Six patients (37.5%) were treated with chemotherapy only, one
      (6.2%) with endocrine therapy only, three (18.8%) with a combination of
      chemotherapy and targeted therapy, and six (37.5%) with a combination of
      endocrine and targeted therapy. Median questionnaire collection rate for the
      total of 12 weeks was 84.6% (interquartile range 44.3-100). The reasons for
      missing data were worsening of disease, forgetting, and device malfunction.
      CONCLUSIONS: Compliance with electronic HRQOL data collection in this cohort was
      acceptable, considering the general ideal collection rate of 70-80%. We are
      conducting a prospective study to determine whether the use of CHES to input
      electronic real-time feedback of HRQOL ratings improves patients' overall HRQOL.

PMID- 30194663
TI  - Efficacy of low-dose daily versus alternate-day prednisolone in frequently
      relapsing nephrotic syndrome: an open-label randomized controlled trial.
AB  - BACKGROUND: While patients with frequently relapsing nephrotic syndrome (FRNS)
      are initially treated with long-term alternate-day prednisolone, relapses and
      adverse effects are common. In an open-label randomized controlled trial, we
      compared the efficacy of therapy with low-dose daily to standard alternate-day
      prednisolone in reducing relapse rates over 12-month follow-up. METHODS:
      Consecutive patients, aged 2-18 years, with FRNS were included. Following therapy
      of relapse, prednisolone was tapered to 0.75 mg/kg on alternate days. Stratifying
      for steroid dependence, patients were randomly assigned to prednisolone at 0.2
      0.3 mg/kg daily or 0.5-0.7 mg/kg alternate day for 12 months. Relapses were
      treated with daily prednisolone, followed by return to intervention. Primary
      outcome was the incidence of relapses. Proportion with therapy failure (>= 2
      relapses in any 6 months or significant steroid toxicity) and sustained
      remission, cumulative prednisolone intake and adverse events were evaluated.
      RESULTS: Patients receiving daily prednisolone (n = 30) showed significantly
      fewer relapses than those on alternate-day therapy (n = 31) (0.55 relapses/person
      year versus 1.94 relapses/person-year; incidence rate ratio 0.28; 95% CI 0.15,
      0.52). Daily therapy was associated with higher rates of sustained remission at 6
      months (73.3 versus 48.4%) and 1 year (60 versus 31.6%; log rank p = 0.013),
      lower rates of treatment failure at 6 months (3.3 versus 32.8%) and 1 year (6.7
      versus 57.4%; p < 0.0001), and lower prednisolone use (0.27 +/- 0.07 versus 0.39
      +/- 0.19 mg/kg/day; p = 0.003). Three and two patients need to receive the study
      intervention to enable sustained remission and prevent treatment failure,
      respectively. CONCLUSIONS: In patients with FRNS, daily administration of low
      dose prednisolone is more effective than standard-dose alternate day therapy in
      lowering relapse rates, sustaining remission, and enabling steroid sparing.

PMID- 30194658
TI  - Intratumoral Heterogeneity in Ductal Carcinoma In Situ: Chaos and Consequence.
AB  - Ductal carcinoma in situ (DCIS) is a non-invasive proliferative growth in the
      breast that serves as a non-obligate precursor to invasive ductal carcinoma. The
      widespread adoption of screening mammography has led to a steep increase in the
      detection of DCIS, which now comprises approximately 20% of new breast cancer
      diagnoses in the United States. Interestingly, the intratumoral heterogeneity
      (ITH) that has been observed in invasive breast cancers may have been established
      early in tumorigenesis, given the vast and varied ITH that has been detected in
      DCIS. This review will discuss the intratumoral heterogeneity of DCIS, focusing
      on the phenotypic and genomic heterogeneity of tumor cells, as well as the
      compositional heterogeneity of the tumor microenvironment. In addition, we will
      assess the spatial heterogeneity that is now being appreciated in these lesions,
      and summarize new approaches to evaluate heterogeneity of tumor and stromal cells
      in the context of their spatial organization. Importantly, we will discuss how a
      growing understanding of ITH has led to a more holistic appreciation of the
      complex biology of DCIS, specifically its evolution and natural history. Finally,
      we will consider ways in which our knowledge of DCIS ITH might be translated in
      the future to guide clinical care for DCIS patients.

PMID- 30194664
TI  - Association of infections and venous thromboembolism in hospitalized children
      with nephrotic syndrome.
AB  - BACKGROUND: Nephrotic syndrome (NS) results in hypercoagulability and increased
      risk of infection. Furthermore, infection increases the risk of venous
      thromboembolism (VTE). Our objective was to determine the prevalence of
      infection, VTE, and the associated outcomes among a cohort of hospitalized
      children with NS. METHODS: All children with NS admitted to 17 pediatric
      hospitals across North America from 2010 to 2012 were included. Prevalence of
      infection and VTE was determined. Wilcoxon rank-sum and logistic regression were
      performed. RESULTS: Seven-hundred thirty hospitalizations occurred among 370
      children with NS. One-hundred forty-eight children (40%) had >= 1 infection (211
      episodes) and 11 (3%) had VTE. Those with VTE had infection more frequently (p =
      0.046) and were younger at NS diagnosis (3.0 vs. 4.0 years; p = 0.008). The most
      common infectious pathogen identified was Streptococcus pneumoniae. The median
      hospital length of stay for those with infection [10 vs 5 days (p < 0.0001)] or
      VTE [22 vs 6 days (p < 0.0001)] was longer than those without either
      complication. Of those with infection, 13% had an intensive care unit (ICU) stay
      compared with 3.3% of those without infection. Median ICU stay was 4 days in
      those with VTE compared to 0 days in those without (p < 0.001). By logistic
      regression, only the number of ICU days was associated with VTE (OR 1.074, 95% CI
      1.013-1.138). CONCLUSIONS: Hospitalized children with NS have high rates of
      infection. Presence of VTE was associated with infection. Both were associated
      with longer hospitalizations and ICU stays.

PMID- 30194666
TI  - [Allways an important subject : Diagnosis and treatment of nail diseases].

PMID- 30194665
TI  - Preliminary feasibility study on differential diagnosis between radiation-induced
      cerebral necrosis and recurrent brain tumor by means of [18F]fluoro-borono
      phenylalanine PET/CT.
AB  - OBJECTIVES: A previous study reported that a differential diagnosis between
      glioblastoma progression and radiation necrosis by 4-borono-2-[18F]-fluoro
      phenylalanine ([18F]FBPA) PET can be made based on lesion-to-normal ratio of
      [18F]FBPA accumulation. Two-dimensional data acquisition mode PET alone system,
      with in-plane resolution of 7.9 mm and axial resolution of 13.9 mm, was used. In
      the current study, we aimed to confirm the differential diagnostic capability of
      [18F]FBPA PET/CT with higher PET spatial resolution by three-dimensional visual
      inspection and by measuring mean standardized uptake value (SUVmean), maximum SUV
      (SUVmax), metabolic tumor volume (MTV), and total lesion (TL) [18F]FBPA uptake.
      METHODS: Twelve patients of glioma (9), malignant meningioma (1),
      hemangiopericytoma (1), and metastatic brain tumor (1) were enrolled. All had
      preceding radiotherapy. High-resolution three-dimensional data acquisition mode
      PET/CT with in-plane resolution of 4.07 mm and axial resolution of 5.41 mm was
      employed for imaging. Images were three-dimensionally analyzed using the PMOD
      software. SUVmean and SUVmax of lesion and normal brain were measured. Lesion MTV
      and TL FBPA uptake were calculated. The diagnostic accuracy of [18F]FBPA PET/CT
      in detecting recurrence (n = 6) or necrosis (n = 6) was verified by clinical
      follow-up. RESULTS: All parameters showed significantly higher values for tumor
      recurrence than for necrosis. SUVmean in recurrence was 2.95 +/- 0.84 vs 1.18 +/-
      0.24 in necrosis (P = 0.014); SUVmax in recurrence was 4.63 +/- 1.23 vs 1.93 +/-
      0.44 in necrosis (P = 0.014); MTV in recurrence was 44.92 +/- 28.93 mL vs 10.66
      +/- 8.46 mL in necrosis (P = 0.032); and mean TL FBPA uptake in recurrence was
      121.01 +/- 50.48 g vs 12.36 +/- 9.70 g in necrosis (P = 0.0029). CONCLUSION: In
      this preliminary feasibility study, we confirmed the possibility of
      differentiating tumor recurrence from radiation necrosis in patients with
      irradiated brain tumors by [18F]FBPA PET/CT using indices of SUVmean, SUVmax,
      MTV, and TL 18FBPA uptake.

PMID- 30194667
TI  - ?

PMID- 30194669
TI  - Biographies.

PMID- 30194668
TI  - Increasing physical activity and healthy diet in outpatients with mental
      disorders: a randomized-controlled evaluation of two psychological interventions.
AB  - INTRODUCTION: While physical activity (PA) can play an important role in the
      treatment of mental disorders (MD), large proportions of patients with MD do not
      meet PA recommendations. The aim of this trial was to evaluate whether structured
      psychological intervention (MoVo-LISA) is effective in helping outpatients with
      MD to increase their level of PA. As active control group (CG) we modified MoVo
      LISA to target healthy diet behavior. METHODS: N = 83 outpatients with MD (F1-F4)
      were randomized to the two conditions. PA (self-report and accelerometry),
      dietary behavior, social-cognitive determinants of health behavior change,
      psychiatric symptoms and health-related quality of life were assessed at
      baseline, 1 and 12 weeks after the intervention. RESULTS: Significant time*group
      interaction effects for objectively measured PA, dietary behavior and fruit and
      vegetable consumption indicated differential effects of the interventions on
      these outcomes. PA increased in the MoVo-LISA group (IG) from baseline to follow
      up while it decreased in CG. IG showed a significant higher level of objectively
      measured PA at follow-up compared to CG. Dietary behavior and fruit and vegetable
      consumption significantly increased from baseline to follow-up in CG, but not IG.
      IG showed a significant increase in some, but not all social cognitive
      determinants of health behavior change. CONCLUSIONS: MoVo-LISA is effective in
      helping outpatients with MD to increase their level of PA in short- and mid-term.
      The used intervention strategies are effective for the promotion of healthy diet
      in patients with MD as well.

PMID- 30194670
TI  - Towards a more accurate future for chlorophyll a and b determinations: the
      inaccuracies of Daniel Arnon's assay.
AB  - A recent publication (Esteban in New Phytol 217:341-342, 2018) describes how the
      use and citation of the assay of chlorophylls a and b extracted in aqueous 80%
      acetone by Arnon (Plant Physiol 2:1-15, 1949) is increasing, even in journals
      with high impact factors. This is a very disconcerting situation: the assay is
      outdated because it relies on the seriously under-estimated extinction
      coefficients of Mackinney (J Biol Chem 140:315-322, 1941), and the assay of
      chlorophylls is one of the most important, and much reported, procedures in
      studies of photosynthesis and related plant biological fields. Using the assay
      has led to the accumulation of masses of inaccurate data and confusion during the
      resolution of some plant biological problems. A summary not only of an accurate
      assay of chlorophylls in aqueous 80% acetone but also of a long-known method to
      correct the data obtained by Arnon's procedure (cf. Porra et al. in Biochim
      Biophys Acta 975:384-394, 1989) is briefly described below together with
      references to reliable assays in this and other solvents by other authors.

PMID- 30194671
TI  - 15N photo-CIDNP MAS NMR on both photosystems and magnetic field-dependent 13C
      photo-CIDNP MAS NMR in photosystem II of the diatom Phaeodactylum tricornutum.
AB  - Diatoms contribute about 20-25% to the global marine productivity and are
      successful autotrophic players in all aquatic ecosystems, which raises the
      question whether this performance is caused by differences in their
      photosynthetic apparatus. Photo-CIDNP MAS NMR presents a unique tool to obtain
      insights into the reaction centres of photosystems (PS), by selective enhancement
      of NMR signals from both, the electron donor and the primary electron acceptor
      molecules. Here, we present the first observation of the solid-state photo-CIDNP
      effect in the pennate diatoms. In comparison to plant PSs, similar spectral
      patterns have been observed for PS I at 9.4 T and PS II at 4.7 T in the PSs of
      Phaeodactylum tricornutum. Studies at different magnetic fields reveal a
      surprising sign change of the 13C photo-CIDNP MAS NMR signals indicating an
      alternative arrangement of cofactors which allows to quench the Chl a donor
      triplet state in contrast to the situation in plant PS II. This unusual quenching
      mechanism is related to a carotenoid molecule in close vicinity to the Chl a
      donor. In addition to the photo-CIDNP MAS NMR signals arising from the donor and
      the primary electron acceptor cofactors, a complete set of signals of the
      imidazole ring ligating to the magnesium of Chl a can be observed.

PMID- 30194673
TI  - Perioperative glucocorticoid stress dosing: a survey of anesthesiologists and
      general internists.

PMID- 30194672
TI  - Accuracy of remote continuous respiratory rate monitoring technologies intended
      for low care clinical settings: a prospective observational study.
AB  - PURPOSE: Altered respiratory rate (RR) has been identified as an important
      predictor of serious adverse events during hospitalization. Introduction of a
      well-tolerated continuous RR monitor could potentially reduce serious adverse
      events such as opioid-induced respiratory depression. The purpose of this study
      was to investigate the ability of different monitor devices to detect RR in low
      care clinical settings. METHODS: This was a prospective method-comparison study
      with a cross-sectional design. Thoracic impedance pneumography (IPG), frequency
      modulated continuous wave radar, and an acoustic breath sounds monitor were
      compared with the gold standard of capnography for their ability to detect RR in
      breaths per minute (breaths.min-1) in awake postoperative patients in the
      postanesthesia care unit. The Bland and Altman method for repeated measurements
      and mixed effect modelling was used to obtain bias and limits of agreement (LoA).
      Furthermore, the ability of the three devices to assist with correct treatment
      decisions was evaluated in Clarke Error Grids. RESULTS: Twenty patients were
      monitored for 1,203 min, with a median [interquartile range] of 61 [60-63] min
      per patient. The bias (98.9% LoA) were 0.1 (-7.9 to 7.9) breaths.min-1 for the
      acoustic monitor, -1.6 (-10.8 to 7.6) for the radar, and -1.9 (-13.1 to 9.2) for
      the IPG. The extent to which the monitors guided adequate or led to inadequate
      treatment decisions (determined by Clarke Error Grid analysis) differed
      significantly between the monitors (P = 0.011). Decisions were correct 96% of the
      time for acoustic, 95% of the time for radar, and 94% of the time for IPG
      monitoring devices. CONCLUSIONS: None of the studied devices (acoustic, IPG, and
      radar monitor) had LoA that were within our predefined (based on clinical
      judgement) limits of +/- 2 breaths.min-1. The acoustic breath sound monitor
      predicted the correct treatment more often than the IPG and the radar device.

PMID- 30194674
TI  - Point-of-care viscoelastic hemostatic testing in cardiac surgery patients: a
      systematic review and meta-analysis.
AB  - PURPOSE: Thromboelastography and rotational thromboelastometry are point-of-care
      (POC) viscoelastic tests used to help guide blood product administration. It is
      unclear whether these tests improve clinical or transfusion-related outcomes. The
      objective of this study was to appraise data from randomized trials evaluating
      the benefit of POC testing in cardiac surgery patients. Primary outcomes were the
      proportion of patients transfused with blood products and all-cause mortality.
      SOURCE: Medline (Ovid), EMBASE (Ovid), CENTRAL (the Cochrane Library-Wiley), Web
      of Science, Biosis, Scopus, and CINAHL databases, as well as clinical trial
      registries and conference proceedings were queried from inception to February
      2018. PRINCIPAL FINDINGS: We identified 1,917 records, 11 of which were included
      in our analysis (8,294 patients). Point-of-care testing was not associated with a
      difference in the proportion of patients transfused with any blood product (risk
      ratio [RR], 0.90; 95% confidence interval [CI], 0.79 to 1.02; I2 = 51%; four
      trials, 7,623 patients), or all-cause mortality (RR, 0.73; 95% CI, 0.47 to 1.13;
      I2 = 5%; six trials, 7,931 patients). Nevertheless, POC testing was weakly
      associated with a decrease in the proportion of patients receiving red blood
      cells (RBC) (RR, 0.91; 95% CI, 0.85 to 0.96; I2 = 0%; seven trials, 8,029
      patients), and heterogeneous reductions in frozen plasma (FP) (RR, 0.58; 95% CI,
      0.34 to 0.99; I2 = 87%; six trials, 7,989 patients) and platelets (RR, 0.66; 95%
      CI, 0.49 to 0.90; I2 = 65%; seven trials, 8,029 patients). Meta-analysis of the
      number of units of RBCs and FP was not possible due to heterogeneity in
      reporting, however POC testing significantly reduced the units of platelets
      transfused (standard mean difference, -0.09; 95% CI, -0.18 to 0.00; four trials,
      7,643 patients). CONCLUSION: Our review indicates that in cardiac surgery
      patients, POC viscoelastic hemostatic testing is not associated with a reduction
      in the proportion of patients receiving any blood product or all-cause mortality.
      However, viscoelastic testing is weakly associated with a reduction in proportion
      of patients transfused with specific blood products. Presently, the benefits
      associated with viscoelastic testing in cardiac surgery patients are
      insufficiently robust to recommend routine implementation of this technology.
      TRIAL REGISTRATION: PROSPERO (CRD4201706577). Registered 11 May 2017.

PMID- 30194675
TI  - Intersex Activists in Israel: Their Achievements and the Obstacles They Face.
AB  - This article focuses on the dynamic between the medical policy on intersex bodies
      and intersex activists in Israel. Recently, in many countries changes have taken
      place in medical guidelines regarding intersex patients and laws that regulate
      medical practices and prohibit irreversible surgeries for intersex babies for
      cosmetic reasons and without the patient's consent. In Israel, intersex activists
      are limited by several factors. On the one hand, they are influenced by the
      achievements of intersex activism around the world but on the other, the
      pathologizing medical discourse and socio-medical practices, which include early
      diagnosis, early irreversible surgeries, and secrecy surrounding intersexed
      bodies, present obstacles to achieving bodily autonomy for intersex individuals
      and social recognition of different sex development. Nevertheless, intersex
      activists are attempting to find different social and media spaces in which to
      achieve public acknowledgement and future bodily autonomy for intersexed people
      and seeking medical professionals' cooperation. Recently, the Israeli Ministry of
      Health published a new circular for intersex/DSD patients, and while it does not
      clearly forbid irreversible surgeries, it provides information about the
      complexities of intersex people and their experience.

PMID- 30194676
TI  - Comparison analysis between haplo identical stem cell transplantation and matched
      sibling donor stem cell transplantation for high-risk acute myeloid leukemia in
      first complete remission.
AB  - In order to compare the effect between haploidentical (HID) stem cell
      transplantation (HSCT) and matched sibling donor (MSD) stem cell transplantation
      for high-risk acute myeloid leukemia (AML) in first complete remission status
      (CR1), we retrospectively studied 170 cases who received stem cell
      transplantation from Jan 2008 to Jul 2015 in Peking University People's Hospital.
      We divided all cases into MSD group (43 cases) and HID (127 cases) group.
      Patients in HID and MSD group displayed similar baseline characteristics except
      for age distribution. There were no statistic differences for overall survival
      (OS), cumulative incidence of relapse, leukemia free survival (LFS),
      transplantation related mortality (TRM) between HID and MSD group. The 3-year OS,
      LFS for all patients was 63.9% and 59.7% respectively. Multivariate analysis
      showed that grade III-IV acute graft versus host disease (aGVHD) was an
      independent risk factor for treatment related mortality (HR=8.134, 95% CI: 3.210
      20.611, P<0.001), monosomy/complex chromosomal karyotype and white blood cell
      count more than 50*109 L-1 were two independent factors for relapse (HR=1.533,
      95% CI: 1.040-2.260, P=0.031) (HR=1.004, 95% CI: 1.001-1.008, P=0.015). Grade III
      IV aGVHD was an independent factor for mortality (HR=3.184, 95% CI: 1.718-5.902,
      P<0.001). These results demonstrated some risk factors for high-risk AML leukemia
      transplantation and indicated for AML patients in CR1 status, haplo stem cell
      transplantation could have the same therapeutic effect as MSD transplantation.

PMID- 30194677
TI  - The intestinal epithelial response to damage.
AB  - The constant renewal of the intestinal epithelium is fueled by intestinal stem
      cells (ISCs) lying at the base of crypts, and these ISCs continuously give rise
      to transit-amplifying progenitor cells during homeostasis. Upon injury and loss
      of ISCs, the epithelium has the ability to regenerate by the dedifferentiation of
      progenitor cells that then regain stemness and repopulate the pool of ISCs.
      Epithelial cells receive cues from immune cells, mesenchymal cells and the
      microbiome to maintain homeostasis. This review focuses on the response of the
      epithelium to damage and the interplay between the different intestinal
      compartments.

PMID- 30194678
TI  - Structural and functional insights into MCR-2 mediated colistin resistance.

PMID- 30194679
TI  - Creeping motion of a solid particle inside a spherical elastic cavity?.
AB  - On the basis of the linear hydrodynamic equations, we present an analytical
      theory for the low-Reynolds-number motion of a solid particle moving inside a
      larger spherical elastic cavity which can be seen as a model system for a fluid
      vesicle. In the particular situation where the particle is concentric with the
      cavity, we use the stream function technique to find exact analytical solutions
      of the fluid motion equations on both sides of the elastic cavity. In this
      particular situation, we find that the solution of the hydrodynamic equations is
      solely determined by membrane shear properties and that bending does not play a
      role. For an arbitrary position of the solid particle within the spherical
      cavity, we employ the image solution technique to compute the axisymmetric flow
      field induced by a point force (Stokeslet). We then obtain analytical expressions
      of the leading-order mobility function describing the fluid-mediated hydrodynamic
      interactions between the particle and the confining elastic cavity. In the quasi
      steady limit of vanishing frequency, we find that the particle self-mobility
      function is higher than that predicted inside a rigid no-slip cavity. Considering
      the cavity motion, we find that the pair-mobility function is determined only by
      membrane shear properties. Our analytical predictions are supplemented and
      validated by fully resolved boundary integral simulations where a very good
      agreement is obtained over the whole range of applied forcing frequencies.

PMID- 30194680
TI  - Coordination of trunk and foot acceleration during gait is affected by walking
      velocity and fall history in elderly adults.
AB  - BACKGROUND: Falling is a significant concern for many elderly adults but
      identifying individuals at risk of falling is difficult, and it is not clear how
      elderly adults adapt to challenging walking. AIMS: The aim of the current study
      was to determine the effects of walking at non-preferred speeds on the
      coordination between foot and trunk acceleration variability in healthy elderly
      adults with and without fall history compared to healthy young adults. METHODS:
      Subjects walked on a treadmill at 80%-120% of their preferred walking speed while
      trunk and foot accelerations were recorded with wireless inertial sensors.
      Variability of accelerations was measured by root mean square, range, sample
      entropy, and Lyapunov exponent. The gait stability index was calculated using
      each variability metric in the frontal and sagittal plane by taking the ratio of
      trunk acceleration variability divided by foot acceleration variability. RESULTS:
      Healthy young adults demonstrated larger trunk accelerations relative to foot
      accelerations at faster walking speeds compared to elderly adults, but both young
      and elderly adults show similar adaption to their acceleration regularity.
      Between group differences showed that elderly adult fallers coordinate
      acceleration variability between the trunk and feet differently compared to
      elderly non-fallers and young adults. DISCUSSION: The current results indicate
      that during gait, elderly fallers demonstrate more constrained, less adaptable
      trunk movement relative to their foot movement and this pattern is different
      compared to elderly non-fallers and healthy young. CONCLUSIONS: Coordination
      between trunk and foot acceleration variability plays an important role in
      maintaining stability during gait.

PMID- 30194681
TI  - Interpretations of the Term "Actionable" when Discussing Genetic Test Results:
      What you Mean Is Not What I Heard.
AB  - In genomic medicine, the familiarity and inexactness of the term "actionable" can
      lead to multiple interpretations and mistaken beliefs about realistic treatment
      options. As part of a larger study focusing on public attitudes toward policies
      for the return of secondary genomic results, we looked at how members of the lay
      public interpret the term "medically actionable" in the context of genetic
      testing. We also surveyed a convenience sample of oncologists as part of a
      separate study and asked them to define the term "medically actionable." After
      being provided with a definition of the term, 21 out of 60 (35%) layperson
      respondents wrote an additional action not specified in the provided definition
      (12 mentioned "cure" and 9 mentioned environment or behavioral change) and 17
      (28%) indicated "something can be done" with no action specified. In contrast, 52
      surveyed oncologists did not mention environment, behavioral change, or cure.
      Based on our findings, we propose that rather than using the term "actionable"
      alone, providers should also say "what they mean" to reduce miscommunication and
      confusion that could negatively impact medical decision-making. Lastly, to guide
      clinicians during patient-provider discussion about genetic test results, we
      provide examples of phrasing to facilitate clearer communication and
      understanding of the term "actionable."

PMID- 30194682
TI  - Simultaneously Improving Mechanical, Formulation, and In Vivo Performance of
      Naproxen by Co-Crystallization.
AB  - Naproxen (NAP), an anti-inflammatory drug belonging to class II of
      Biopharmaceutic Classification System, has low aqueous solubility and dissolution
      rate which limit its oral bioavailability. The focus of this investigation was to
      assess the impact of co-crystallization in improving the physico-mechanical and
      in vivo performance of NAP. NAP was co-crystallized using nicotinamide as a co
      former employing liquid-assisted grinding method and characterized by intrinsic
      dissolution rate, DSC, and PXRD. Prepared co-crystal exhibited improved
      physicochemical and mechanical properties. Mechanical behavior of NAP and
      developed co-crystal was analyzed by drawing tabletability curves. Over the
      entire range of used compaction pressure, NAP showed poor tensile strength (< 2
      MPa) which resulted in lamination and capping in some tablets. In contrast,
      tensile strength of co-crystal gradually increased with pressure and was ~ 1.80
      times that of NAP at 5000 psi. Intrinsic dissolution profile of co-crystal showed
      a more than five and twofold faster dissolution than NAP in 0.1 M HCl and
      phosphate buffer pH 7.4 at 37 degrees C. In addition, formulation of co-crystal
      powder into tablets by direct compression demonstrated enhanced dissolution
      profiles (~ 43% in 0.1 M HCl and ~ 92% in phosphate buffer pH 7.4) in comparison
      to a marketed product, Neoprox (~ 25 and ~ 80%) after 60 min. In a single dose
      oral exposure study conducted in sheep, co-crystal showed more than 1.5-fold
      increase in AUC and Cmax. In conclusion, co-crystals of NAP illustrated better
      tabletability, in vitro and in vivo performance.

PMID- 30194683
TI  - Decreased intramuscular calcium hydroxyapatite implant resorption in a murine
      model of osteoporosis.
AB  - OBJECTIVE: Calcium hydroxyapatite (CaHA) is a common material for vocal fold
      injection augmentation. Durability is variable, and factors involved in implant
      longevity are not understood. Animal models of osteoporosis show decreased bone
      density and increased mineral liberation, suggesting CaHA retention may be
      altered in these conditions. STUDY DESIGN: Prospective murine investigation.
      METHODS: Fourteen skeletally mature, 10-month-old female Sprague-Dewley rats were
      treated by one of three interventions: oophorectomy, laparotomy without
      oophorectomy (sham), or monthly risedronate injection (90 MUg/kg, subcutaneous).
      CaHA was implanted into the right lateral thigh muscle in all animals at the time
      of procedure or first risedronate injection. After 17 weeks, all rats were
      sacrificed, and the residual CaHA isolated from excised lateral thigh muscle
      through incubation in a 900  degrees C calcinator for 9 hours. RESULTS: Mean CaHA
      mass remaining in the oophorectomy group was 65.9 (standard deviation +/- 16.1)
      mg, compared to 44.4 +/- 10.0 mg CaHA in the risedronate group and 48.6 +/- 7.5
      mg in the sham group. One-way analysis of variance found a statistically
      significant difference between the oophorectomy and risedronate groups but not
      between the sham and other groups, F(2,11) = 4.404, P = 0.039. CONCLUSION:
      Persistent estrogen deficiency in a murine model of osteoporosis demonstrated
      decreased rate of CaHA resorption. This suggests that hormone alterations
      associated with osteoporosis may alter the longevity of CaHA implant resorption
      through an uncertain mechanism. LEVEL OF EVIDENCE: NA. Laryngoscope, 2576-2580,
      2018.

PMID- 30194684
TI  - Association Between Age and Patient-Reported Changes in Voice and Swallowing
      After Thyroidectomy.
AB  - OBJECTIVES: Despite intact recurrent laryngeal nerves, patient-reported voice and
      swallowing changes are common after thyroidectomy. The association between
      patient age or frailty status and these changes is unknown. The aim of this study
      was to evaluate the impact of age and frailty on the incidence of voice and
      swallowing alterations after thyroidectomy. METHODS: We performed an
      institutional review board (IRB)-approved retrospective review of consecutive
      patients who underwent total thyroidectomy with intraoperative recurrent
      laryngeal nerve (RLN) monitoring at a single institution between January 2014 and
      September 2016. Patients with RLN injury were excluded. After data extraction, a
      modified frailty index (mFI) was calculated for each patient. The association
      among risk factors, including age, mFI, prior history of neck surgery, frequent
      voice use, presence of malignancy or gastroesophageal reflux disease, and smoking
      status and reported voice and/or swallowing changes was examined. RESULTS: Of 924
      patients undergoing thyroidectomy, 148 (16.0%) reported only changes in voice; 52
      (5.6%) reported only difficulty in swallowing; and 26 (2.8%) reported changes
      with both voice and swallowing. On multivariate analysis, we found a significant
      increase in voice or swallowing alterations up to the age of 50 years (5%
      increased odds per year), after which these changes plateaued. We found that mFI
      was not associated with voice or swallowing changes. CONCLUSION: Age >= 50 years
      is independently associated with the development of voice or swallowing changes
      after thyroidectomy, despite intact RLN. Additional prospective studies are
      needed to validate these findings, further define this association, and identify
      risk factors for developing these changes. LEVEL OF EVIDENCE: 2b. Laryngoscope,
      2018.

PMID- 30194685
TI  - Changes in quaternary structure cause a kinetic asymmetry of glutamate racemase
      catalyzed homocysteic acid racemization.
AB  - Glutamate racemases (GR) catalyze the racemization of d- and l-glutamate and are
      targets for the development of antibiotics. We demonstrate that GR from the
      periodontal pathogen Fusobacterium nucleatum (FnGR) catalyzes the racemization of
      d-homocysteic acid (d-HCA), while l-HCA is a poor substrate. This
      enantioselectivity arises because l-HCA perturbs FnGR's monomer-dimer equilibrium
      toward inactive monomer. The inhibitory effect of l-HCA may be overcome by
      increasing the total FnGR concentration or by adding glutamate, but not by
      blocking access to the active site through site-directed mutagenesis, suggesting
      that l-HCA binds at an allosteric site. This phenomenon is also exhibited by GR
      from Bacillus subtilis, suggesting that enantiospecific, "substrate"-induced
      dissociation of oligomers to form inactive monomers may furnish a new inhibition
      strategy.

PMID- 30194686
TI  - A large rheumatoid nodule mimicking hepatic malignancy.
AB  - Approximately 40% of patients with rheumatoid arthritis (RA) suffer from extra
      articular manifestations [1], including appearance of rheumatoid nodules. These
      are found predominantly along the extensor surfaces of the forearm and the elbow,
      and less often, in visceral organs [2]. This article is protected by copyright.
      All rights reserved.

PMID- 30194688
TI  - Cosmetic dentistry: A socioethical evaluation.
AB  - Cosmetic dentistry is a divisive discipline. Within discourses that raise
      questions of the purpose of the dental profession, cosmetic dentistry is
      frequently criticised on the basis of it being classified as a non-therapeutic
      intervention. This article re-evaluates this assertion through examination of
      ethics of care of the self, healthcare definitions and the social purpose of
      dentistry, finding the traditional position to be wanting in its conclusions. The
      slide of dentistry from a healthcare vocation towards being a predominantly
      business-focused interaction between clinician and consumer conflicts with
      traditional notions of dentistry as a profession. Whilst it is undeniable that
      cosmetic dental treatment particularly lends itself to the commercial paradigm,
      this is not exclusive to this area of professional practice. The cultural basis
      of dental appearance and the potential of the dental profession to exert coercive
      pressure upon the public to undergo treatment that is based upon social norms is
      discussed. This essay concludes that cosmetic dentistry is undeniably part of the
      professional purpose of 21st Century dentistry. However, the caveat that may be
      placed upon this, is that this status is conditional upon the professional
      conduct of dental practitioners remaining resilient to commercial practices not
      compatible with professional obligations.

PMID- 30194689
TI  - Cognitive outcomes in children born very preterm are not improving.

PMID- 30194687
TI  - Anti-TNF therapy for genital fistulas in female patients with Crohn's disease: a
      nationwide study from the Groupe d'Etude Therapeutique des Affections
      Inflammatoires du tube Digestif (GETAID).
AB  - BACKGROUND: Genital fistulas represent a devastating complication of Crohn's
      disease. Only studies with small sample sizes have evaluated the efficacy of anti
      TNF therapy for this complication. AIMS: To assess the efficacy of anti-TNF
      therapy for genital fistulas complicating Crohn's disease and to identify
      predictive factors associated with clinical response at 1 year. METHODS:
      Consecutive patients treated with anti-TNF therapy for genital fistulas
      complicating Crohn's disease from 1999 to 2016 in 19 French centres from the
      Groupe d'Etude Therapeutique des Affections Inflammatoires du tube Digestif were
      included in a retrospective cohort study. Outcome was clinical fistula closure at
      1 year. RESULTS: Among the 204 women with genital fistulas who received anti-TNF
      therapy, 131 were analysed. The first anti-TNF given was infliximab (79%),
      adalimumab (20%), or certolizumab (1%). At start of anti-TNF therapy, 56% of
      patients had seton drainage and 53% had concomitant immunosuppressive treatment.
      A complementary surgery was performed during the first year in 10 patients (8%).
      At 1 year, 37% of patients had complete clinical fistula closure, 22% had a
      partial response, and 41% had no response. Among patients without complementary
      surgery, 34% (41/121) had complete clinical fistula closure. Only complementary
      surgery was associated with better response on multivariate analysis (adjusted
      relative risk: 2.02, 95% CI: 1.25-3.26, P = 0.0043). CONCLUSIONS: In the anti-TNF
      era, approximately one-third of patients with genital fistula in Crohn's disease
      had complete fistula closure at 1 year. Collaboration between surgeons and
      gastroenterologists appears to be very important to improve the rate of fistula
      closure.

PMID- 30194690
TI  - The relative importance of dissatisfaction, overvaluation and preoccupation with
      weight and shape for predicting onset of disordered eating behaviors and
      depressive symptoms over 15 years.
AB  - OBJECTIVE: The aim of this study was to examine the relative importance of
      dissatisfaction, overvaluation, and preoccupation with body weight and shape in
      predicting increases in disordered eating behaviors and depressive symptoms from
      adolescence through to early adulthood. METHOD: The study involved 1,830
      participants (60% female) who completed the Project EAT survey during adolescence
      (mean age = 14.90 years, SD = 1.65 years) and again, 15 years later, in early
      adulthood. Participants provided assessments of dissatisfaction, overvaluation
      and preoccupation with weight and shape, as well as disordered eating and
      depressive symptoms at both time points. RESULTS: The three aspects of body image
      had distinct patterns of association with the outcomes both concurrently and
      longitudinally. Dissatisfaction predicted depressive symptoms as well as a wide
      range of disordered eating outcomes, including dieting, unhealthy weight control
      behaviors (UWCBs), and binge eating, particularly in female participants.
      Preoccupation was associated with all of these disordered eating behaviors (but
      not with depressive symptoms) and was notably the strongest predictor of dieting
      and UWCBs in female participants. Overvaluation was associated with both
      disordered eating and depressive symptoms, although typically was a less potent
      predictor of difficulties than the other aspects of body image. DISCUSSION:
      Dissatisfaction, overvaluation, and preoccupation are related but make distinct
      contributions to clinically significant outcomes. Models of eating disorders
      should move beyond focusing exclusively on dissatisfaction or overvaluation
      toward a broader conceptualisation of body image. Findings from this study
      particularly suggest the importance of considering preoccupation with weight and
      shape.

PMID- 30194692
TI  - Review article: an analysis of safety profiles of treatments for diarrhoea
      predominant irritable bowel syndrome.
AB  - BACKGROUND: Irritable bowel syndrome (IBS) is multifactorial in nature, and a
      wide range of therapies is available to manage symptoms of this common disorder.
      AIM: To provide an overview of the safety of interventions that may be used to
      manage patients with diarrhoea-predominant IBS (IBS-D). METHODS: Medline and
      Embase database searches (through 02 May 2018) to identify clinical studies that
      evaluated treatment safety and/or efficacy in adults with IBS-D. RESULTS: IBS-D
      treatments include dietary modification, probiotics, serotonin receptor
      antagonists, opioid receptor agonists and antagonists, nonsystemic antibiotics,
      bile acid sequestrants, antidepressants, and complementary and alternative
      therapies. These treatments vary in administration frequency (eg, daily; short
      course therapy) and target various pathophysiologic factors. Safety profiles vary
      considerably by treatment among IBS-D therapies. The number needed to harm
      (defined as the number of patients treated to encounter an adverse event) was
      lowest (worse) for antidepressants (8.5) and highest (best) for probiotics (35),
      and the number needed to harm (defined as the number of patients who discontinued
      due to an adverse event) was lowest for tricyclic antidepressants (9) and highest
      for rifaximin (8971). Notable safety concerns with IBS-D treatments include
      pancreatitis with eluxadoline, ischaemic colitis and serious complications of
      constipation with alosetron, and cardiac adverse events with loperamide and
      tricyclic antidepressants. Treatment decisions need to account for medication
      risks and adverse events for each patient. CONCLUSIONS: Multiple treatment
      options are now available for patients with IBS-D. However, the safety profiles
      of these agents vary widely by number needed to harm value. Providers should
      consider both safety and efficacy of a specific intervention when determining how
      best to manage patients' IBS-D symptoms.

PMID- 30194691
TI  - Changing prognosis of oral cancer: An analysis of survival and treatment between
      1973 and 2014.
AB  - OBJECTIVES/HYPOTHESIS: Oral cavity cancer is the most commonly occurring
      malignancy of the head and neck. There are limited data suggesting a change in
      prognosis of oral cavity cancers. We aimed to evaluate temporal trends in
      demographics, treatment, and prognosis of oral cavity cancer diagnosed between
      1973 and 2014 inclusive. STUDY DESIGN: Retrospective database analysis. METHODS:
      A retrospective study of 16,030 adult patients diagnosed with oral cavity cancer
      between 1973 and 2014 inclusive and treated surgically in the Surveillance,
      Epidemiology, and End Results (SEER) 9 registry was conducted. A supplemental
      analysis was conducted using data from the National Cancer Database. Multivariate
      Cox survival regressions and univariate Kaplan-Meier analyses were conducted.
      RESULTS: The prognosis of both early- and late-stage disease has significantly
      improved between 1973 and 2014. Among patients with early-stage disease, 3-year
      survival increased from 78.0% (standard error [SE] = 1.3) for those diagnosed
      from 1973 to 1980 to 92.2% (SE = 1.1) for those diagnosed from 2011 to 2014.
      Among patients with late-stage disease, 3-year survival ranged from 51.9% (SE =
      1.5) for those diagnosed from 1973 to 1980 to 70.3% (SE = 1.9) for those
      diagnosed from 2011 to 2014. For patients with late-stage disease, this improved
      prognosis occurred in tandem with increasing usage of chemoradiotherapy as
      adjuvant therapy. There has also been increasing utilization of neck dissection
      for early- and late-stage disease, along with higher nodal yields from performed
      dissections. CONCLUSIONS: The prognosis of oral cavity cancer has improved
      significantly from the early 1970s to recent years. In late-stage oral cancer,
      this change has been associated with an increased use of adjuvant therapy and
      adjuvant chemoradiotherapy in particular. LEVEL OF EVIDENCE: 4 Laryngoscope,
      2018.

PMID- 30194693
TI  - Quantitative approaches of nanofibers organization for biomedical patterned
      nanofibrous scaffold by image analysis.
AB  - This study proposes a novel design of a laboratory built static collector using
      the 3D printing technology. This new collector produces aligned-to-random
      nanofibers in nanofibrous scaffold through electrospinning process. A design of
      experiment (DOE), based on response surface, analyzes the effect of the main
      process parameters; concentration, voltage, and distance; on the responses
      diameter and orientation. A quantifying approach has been used to investigate the
      orientation of nanofibers in the produced patterned scaffold through Fourier
      transforms method. The obtained results have proven a good potential to be used
      in tissue engineering application, especially for cells requiring specific
      guidance. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2963
      2972, 2018.

PMID- 30194694
TI  - A Population-Based Analysis of Nodal Metastases in Esthesioneuroblastomas of the
      Sinonasal Tract.
AB  - OBJECTIVE: Esthesioneuroblastoma is an uncommon malignancy of the sinonasal tract
      arising from the olfactory epithelium. Surgical management of the primary site,
      often via an endoscopic approach, with or without adjuvant radiation, is often
      curative. There is growing but ultimately limited data regarding management of
      the neck and the risk of nodal metastases. In this study, we examine the
      incidence and patterns of esthesioneuroblastoma-related cervical nodal metastases
      using the Surveillance, Epidemiology, and End Results (SEER) database. METHODS:
      The SEER registry was queried for all patients with esthesioneuroblastomas
      diagnosed between 1973 and 2012. Patient data was then analyzed with respect to
      age, sex, race, modified Kadish stage, grade, survival functions, and nodal
      disease including specific nodal basins. RESULTS: Three hundred and eighty-one
      cases of esthesioneuroblastoma with information on nodal metastases were
      identified. The overall cervical nodal metastasis rate was 8.7%. Level II
      metastases were most common (6.6%). A total of 4.5% of cases presented with
      multiple positive nodal basins. Male sex (P = 0.009) and higher tumor grade (P =
      0.009) correlated with the presence of level II metastases. There was no
      association of primary tumor site to the presence of nodal metastases (P > 0.05).
      The presence of nodal disease significantly predicted poorer overall (P = 0.001)
      and disease-specific survival (P = 0.017). CONCLUSION: The incidence of nodal
      metastases in esthesioneuroblastoma at diagnosis is rare, and elective management
      of the neck remains controversial. Primary tumor site does not appear to predict
      metastases at specific nodal basins. Higher tumor grade may be a harbinger of
      eventual nodal metastases. LEVEL OF EVIDENCE: NA. Laryngoscope, 2018.

PMID- 30194695
TI  - Associations between postpartum depression and hypertensive disorders of
      pregnancy.
AB  - OBJECTIVE: To identify possible relationships between postpartum depression and
      hypertensive disorders of pregnancy (HDP), as well as the associated risk factors
      for developing postpartum depression. METHODS: The present prospective
      descriptive cross-sectional study was conducted among postpartum women who
      attended a public maternity hospital in Brazil between January 15, 2015, and
      January 15, 2017. The diagnosis and severity of HDP were based on blood pressure
      measurements (systolic >=140 mm Hg or diastolic >=90 mm Hg), proteinuria,
      clinical findings, and laboratory findings. A group of normotensive women was
      also included. The Edinburgh Postnatal Depression Scale was used to assess the
      risk of postpartum depression. RESULTS: Of 168 participants (42 with HDP and 126
      normotensive), 40 (23.8%) women displayed depressive symptoms (25 normotensive
      and 15 with HDP). The probability of postpartum depression correlated with a
      diagnosis of HDP (Spearman correlation coefficient [rS ] 0.219; P=0.004);
      premonitory signs of eclampsia (rS 0.171; P=0.027); magnesium sulfate therapy (rS
      0.199; P=0.010); diastolic blood pressure (rS 0.165; P=0.033); and use of milk
      formula during hospitalization (rS 0.152; P=0.048). CONCLUSION: Women diagnosed
      with HDP were more likely to have depressive symptoms than their normotensive
      counterparts.

PMID- 30194696
TI  - Low-carbohydrate diets for overweight and obesity: a systematic review of the
      systematic reviews.
AB  - Low-carbohydrate diets are being widely recommended, but with apparently
      conflicting evidence. We have conducted a formal systematic review of the
      published systematic reviews of RCTs between low-carbohydrate vs. control (low
      fat/energy-restricted) diets in adults with overweight and obesity. In MEDLINE,
      Embase, Web of Knowledge and Cochrane Database of Systematic Reviews, searched
      from inception to September 2017, we identified 12 systematic reviews, 10 with
      meta-analyses. Differences in methods, study quality, weight change and citations
      of published systematic reviews were assessed by AMSTAR-2. Review methods varied
      in definitions of low-carbohydrate diet, databases searched and bias assessment.
      Overall review quality was high in two, moderate in three, critically low in
      seven. Among meta-analyses, 4/5 with critically low quality showed low
      carbohydrate diet superiority for weight loss (0.7-4.0 kg), while high quality
      meta-analyses reported little or no difference between diets. Greater numbers of
      participants correlated with smaller differences in weight loss (r = 0.73, p =
      0.03). More citations correlated with lower review quality (rho = -0.9, p =
      0.037), with larger differences in weight loss (rho = -0.9, p = 0.037), and with
      journal impact factor (rho = 1.0, p = 0.01). In conclusion, publication
      acceptance and citations appear to favour apparently larger effect sizes above
      methodological quality. Better quality reviews and RCTs are needed, before
      recommending low-carbohydrate diets as preferred to other approaches for energy
      restriction.

PMID- 30194697
TI  - Enhanced interdisciplinary communication: development of an interactive thyroid
      nodule/cancer disease map.
AB  - OBJECTIVES: Deficits related to inadequate clinical communication can result in
      incorrect diagnoses, inappropriate surgery, incorrect disease stratification,
      pathologic reporting, and/or interpretation. There are currently no validated or
      defined solutions to disease-specific communication with regard to thyroid care.
      METHODS: We propose a solution that could ameliorate problems arising from
      inadequate disease-specific communications between physicians through the
      development of a thyroid disease-specific database, the Thyroid Care
      Collaborative. RESULTS: To improve the quality of thyroid nodule and cancer care,
      we have developed an imaging module for enhanced reporting of ultrasound,
      cytologic, surgical, and pathologic details that are obtained during the workup
      and treatment of a patient. CONCLUSION: The main advantages of this disease
      specific, dynamic, three-dimensional, anatomic disease map are: 1) portability
      across institutions and disciplines, 2) disease specificity to thyroid nodule and
      cancer care, and 3) ability to trigger more detailed evaluation or reconciliation
      of any change in a patient's status regarding the nature or the extent of a
      patient's disease. The first and second advantages above have been identified as
      areas representing opportunities for quality improvement in health informatics
      research. Laryngoscope, 2018.

PMID- 30194698
TI  - GC-MS analysis of terpenes from Sicilian Pistacia vera L. oleoresin. A source of
      biologically active compounds.

PMID- 30194699
TI  - Mesenchymal stem cell interacted with PLCL braided scaffold coated with poly-l
      lysine/hyaluronic acid for ligament tissue engineering.
AB  - The challenge of finding an adapted scaffold for ligament tissue engineering
      remains unsolved after years of researches. A technology to fabricate a
      multilayer braided scaffold with flexible and elastic poly (l-lactide-co
      caprolactone) (PLCL 85/15) has been recently pioneered by our team. In this
      study, polyelectrolyte multilayer films (PEM) with poly-l-lysine (PLL)/
      hyaluronic acid (HA) were deposited on this scaffold. After PEM modification,
      polygonal (PLL) and particle-like (HA) structures were present on the braided
      scaffold with no significant variation of fibers Young's modulus. Wharton's jelly
      mesenchymal stem cells (WJ-MSC) and bone marrow mesenchymal stem cells (BM-MSC)
      showed good metabolic activity on scaffolds. They presented a spindled shape
      along the fiber longitudinal direction, and crossed the fibers to form cell
      bridges. Collagen type I, collagen type III, and tenascin-C secreted by MSCs were
      detected on day 14. Moreover, one-layer modified scaffold presented increased
      chemotaxis. As a conclusion, our results indicate that this braided PLCL scaffold
      with one-layer PEM modification shows inspiring potential with satisfying
      mechanical properties and biocompatibility. It opens new perspectives to
      incorporate growth factors within PEM-modified braided PLCL scaffold for ligament
      tissue engineering and to recruit endogenous cells after implantation. (c) 2018
      Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 3042-3052, 2018.

PMID- 30194701
TI  - The influence of heart failure on the pharmacokinetics of cardiovascular and non
      cardiovascular drugs: a critical appraisal of the evidence.
AB  - Prescribing in heart failure (HF), a common disease state that predominantly
      affects the older population, is often a challenging task because of the dynamic
      nature of the condition, requiring frequent monitoring and medication review, the
      presence of various comorbidities, and the frailty phenotype of many patients.
      The significant alterations in various organs and tissues occurring in HF,
      particularly the reduced cardiac output with peripheral hypoperfusion and the
      structural and functional changes of the gastrointestinal tract, liver and
      kidney, might affect the pharmacokinetics of several drugs. This review
      critically appraises the results of published studies investigating the
      pharmacokinetics of currently marketed cardiovascular and selected non
      cardiovascular drugs in HF patients and control groups, identifies gaps in the
      current knowledge, and suggests avenues for future research in this complex
      patient population.

PMID- 30194700
TI  - Unveiling the transcriptional control of pleiotropic drug resistance in
      Saccharomyces cerevisiae: Contributions of Andre Goffeau and his group.
AB  - Studies in the yeast Saccharomyces cerevisiae have provided much of the basic
      detail underlying the organization and regulation of multiple or pleiotropic drug
      resistance gene network in eukaryotic microbes. As with many aspects of yeast
      biology, the initial observations that drove the eventual molecular
      characterization of multidrug resistance gene were provided by genetics. This
      review focuses on contributions from the laboratory of Dr. Andre Goffeau that
      uncovered key aspects of the transcriptional regulation of these multidrug
      resistance genes. Andre's group made many seminal discoveries that helped lead to
      the current picture we have of how eukaryotic microbes respond to and deal with a
      variety of antifungal agents. The importance of the transcriptional contribution
      to antifungal drugs is illustrated by the large number of drug resistant mutants
      found in several yeast species that lead to increased activity of transcriptional
      regulators. The characterization of the Saccharomyces cerevisiae PDR1 gene by the
      Goffeau group provided the first molecular basis explaining the link between this
      hyperactive transcription factor and drug resistance.

PMID- 30194702
TI  - Initial presentation of human papillomavirus-related head and neck cancer: A
      retrospective review.
AB  - OBJECTIVE: Human papillomavirus (HPV) has been identified as a risk factor for
      oropharyngeal squamous cell carcinoma (OPSCC) and a cause of the recent dramatic
      rise in the incidence of this disease. HPV-positive OPSCC typically affects a
      younger population and has no validated screening test. This study aims to
      outline the common presenting signs of HPV-positive OPSCC. METHODS: We conducted
      a retrospective single-institution review on 370 patients who were treated at the
      Icahn School of Medicine at Mount Sinai, New York City, between April 2007 and
      November 2015 for OPSCC. We included patients with newly diagnosed OPSCC and
      sufficient history and physical data in the final analysis. Univariate analysis
      was used to compare HPV-positive and HPV-negative cohorts for demographics, tumor
      location, tumor staging, initial presentation and symptoms, and physical exam
      findings. RESULTS: Two hundred and seven patients met the inclusion criteria. The
      most common initial symptoms for OPSCC were neck mass (51.7%) and sore throat
      (13.0%). The HPV-positive cohort was more likely to present with a chief
      complaint of neck mass compared to the HPV-negative cohort (56.1% vs. 22.2%; P =
      0.0015). A positive neck exam was associated with HPV-positive status (73.9% vs.
      40.7%; P = 0.0012). CONCLUSION: HPV-positive OPSCC is an incipient epidemic,
      poised to surpass cervical cancer as the most common HPV-related cancer by 2020.
      Initial presenting signs may often be mistaken for benign processes. This study
      provides physicians with a better understanding of initial presentation of
      patients with HPV-positive OPSCC, leading to earlier diagnosis and improved
      outcomes. LEVEL OF EVIDENCE: 4. Laryngoscope, 2018.

PMID- 30194703
TI  - Education disparities in young people with and without neurodisabilities.
AB  - AIM: To examine key outcomes in the education of young people with and without
      neurodisabilities, and to investigate additional disparities in educational
      achievement in relation to socio-economic background. METHOD: Data were collected
      on 2488 Canadian children (age range 10-11y) in 1994 and 1995 from the National
      Longitudinal Survey of Children and Youth whom were followed for 14 years. We
      performed separate, discrete-time survival analysis to investigate the effects of
      having a neurodisability on high school completion, enrolment in post-secondary
      education (PSE), and PSE completion. RESULTS: The baseline prevalence of
      neurodisabilities was 12%. Fewer children with neurodisabilities completed high
      school or enrolled in PSE, compared to children without neurodisabilities,
      irrespective of parental education. The likelihood that students with
      neurodisabilities completed PSE differed according to their parents' education:
      students with neurodisabilities living in less-educated families were about half
      as likely to complete PSE themselves. INTERPRETATION: Children with
      neurodisabilities receive less education than children without neurodisabilities.
      Children from families with low educational attainment appear to be particularly
      vulnerable. WHAT THIS PAPER ADDS: Twelve per cent of children in Canada aged 10
      years to 11 years have a neurodisability. High school completion rate was 70% for
      children with neurodisabilities versus 94% for children without
      neurodisabilities. Children with neurodisabilities from less-educated families
      are particularly vulnerable to lower educational achievement.

PMID- 30194704
TI  - Snoring and carotid artery disease: A new risk factor emerges.
AB  - OBJECTIVES/HYPOTHESIS: Previous studies have identified a relationship between
      snoring, carotid intima media thickening, and the presence of atherosclerosis.
      This study examines the correlation between snoring and carotid artery disease
      through use of duplex ultrasound identifying greater than 50% internal carotid
      artery stenosis. STUDY DESIGN: Prospective cohort study. METHODS: Patients
      presenting to three academic vascular laboratories for carotid duplex examination
      completed the following surveys: demographic information, assessment of risk
      factors for carotid stenosis, assessment of history of obstructive sleep apnea,
      or continuous positive airway pressure use and Snoring Outcomes Survey. Patients
      were categorized into 2 groups based on the presence or absence of carotid
      disease. Data were analyzed by univariate contingency tables and logistic
      regression analysis. RESULTS: Five hundred one patients completed the survey, of
      whom 243/501 (49%) had evidence of carotid occlusive disease. On univariate
      analysis, smoking, hypertension, heart disease, hypercholesterolemia, diabetes,
      and stroke all correlated with greater than 50% carotid stenosis. Multivariate
      analysis indicated that snorers were significantly more likely to have carotid
      disease. Three hundred twenty-seven participants were thought to have primary
      snoring. On univariate analysis, snorers were found to be significantly more
      likely to have carotid disease. After adjustment for covariates, snoring was not
      significant for carotid disease. However, multivariate analysis showed snorers to
      be significantly more likely to have bilateral carotid disease. CONCLUSIONS: This
      study shows a potential relationship between snoring and bilateral carotid artery
      stenosis greater than 50%; snorers have risk of carotid stenosis twice that of
      nonsnorers. Further investigation is warranted to better elucidate this
      relationship. LEVEL OF EVIDENCE: 2b Laryngoscope, 2018.

PMID- 30194705
TI  - A P-P Bond as a Redox Reservoir and an Active Reaction Site.
AB  - The carbonylation of a nickel(II) anilido species 2 led to the formation of a
      dinickel(0)-CO complex (P2 P-PP2 ){Ni(CO)}2 3 with a P-P bond along with
      isocyanate generation. In this reaction, the central phosphide moiety of an
      anionic PPP ligand (PPP- =- P[2-Pi Pr2 C6 H4 ]2 ) acts as a single-electron donor
      to form a P radical. Alternatively, 3 can be synthesized from the reduction of
      (PPP)NiCl (1) in the presence of CO; thus, the reaction proceeds by radical
      coupling of a . P-Ni0 -CO species. The reverse reaction occurred to generate 1
      when 3 was treated with AgCl. Since the P-P bond is light-sensitive, its
      homolysis is possible and was explored by EPR spectroscopy and DFT analysis.
      Finally, various bond-activation reactions of 3 occurred under visible-light
      conditions, thus indicating that a P-P bond can act as an active reaction site.

PMID- 30194706
TI  - Significant orbital and intracranial complications from balloon sinus dilation as
      a stand-alone and powered dissector-assisted procedure.
AB  - Chronic rhinosinusitis is one of the most common chronic conditions affecting
      millions of people in the United States every year. Balloon sinus dilation is a
      minimally invasive intervention that was introduced as a possible alternative to
      endoscopic sinus surgery (ESS). In select patients, balloon dilation has been
      advocated as a relatively safe procedure with comparable efficacy to traditional
      ESS. Over the past 12 months, significant intracranial and intraorbital
      complications have been observed on five patients who underwent balloon sinus
      dilation as a stand-alone procedure, as well as what could be termed a power
      dissector-assisted balloon dilation procedure, obviating the need for a wide
      sinusotomy or any significant ethmoid surgery, which are typically performed to
      establish anatomical landmarks before the introduction of power instruments into
      dependent sinus cavities. Laryngoscope, 2455-2459, 2018.

PMID- 30194707
TI  - Ultrastructural investigations on spermatogenesis and spermatozoan morphology in
      the endangered Adriatic sturgeon, Acipenser naccarii (Chondrostei,
      Acipenseriformes).
AB  - Spermatogenesis was investigated in the Adriatic sturgeon, Acipenser naccarii, by
      light and electron microscopy. The testis of the unrestricted type had a germinal
      compartment composed of lobules containing germ cells and Sertoli cells, and
      separated by a basal lamina from the interstitial compartment, in which Leydig
      and myoid cells were detected for the first time in Acipenseridae.
      Spermatogenesis occurred in spermatocysts produced when Sertoli cells became
      associated with type A spermatogonia of subsequent generations, which produced a
      clone of synchronized aligned spermatogonia. In primary spermatocytes at zygo
      pachytene stage, the large spherical nucleus contained synaptonemal complexes.
      The smaller secondary spermatocytes were ovoid with a central round nucleus and
      scarce cytoplasm. Spermatids were interconnected by cytoplasmic bridges until
      early spermiogenesis. Chromatin initially condensed as long, twisted, and
      nonhomogeneous fibers and finally as a compact structure made of thick filaments.
      Early spermatids showed the flagellum, the primordia of centriole complex and of
      "implantation fossa," followed by the acrosomal vesicle formed by Golgi complexes
      and a fibrous body associated to centriole complex. The spermatozoan head had 10
      postero-lateral projections and a trapezoidal nucleus, a cylindrical midpiece
      with six to eight mitochondria, the centriole complex, and a "9 + 2" flagellum
      with a pair of lateral fins. Three helical endonuclear canals crossed the nucleus
      from the acrosome base to the implantation fossa; their spiralization and that of
      chromatin fibers suggest a spiral twisting of the nucleus during spermiogenesis.
      The Sertoli cells performed phagocytosis of degenerating spermatids and
      spermatozoa. Significant interindividual differences were detected in most
      morphological parameters of spermatozoa. Data on spermatogenesis in A. naccarii
      and morphometric measurements on mature spermatozoa provide information about the
      reproductive biology of the species useful not only for phylogenetic studies but
      also for evaluation of sperm quality for artificial reproduction projects and
      restocking of this and other critically endangered sturgeon species.

PMID- 30194708
TI  - Review article: drug-induced liver injury in the context of nonalcoholic fatty
      liver disease - a physiopathological and clinical integrated view.
AB  - BACKGROUND: Nonalcoholic fatty disease (NAFLD) is the most common liver disease,
      since it is strongly associated with obesity and metabolic syndrome pandemics.
      NAFLD may affect drug disposal and has common pathophysiological mechanisms with
      drug-induced liver injury (DILI); this may predispose to hepatoxicity induced by
      certain drugs that share these pathophysiological mechanisms. In addition, drugs
      may trigger fatty liver and inflammation per se by mimicking NAFLD
      pathophysiological mechanisms. AIMS: To provide a comprehensive update on (a)
      potential mechanisms whereby certain drugs can be more hepatotoxic in NAFLD
      patients, (b) the steatogenic effects of drugs, and (c) the mechanism involved in
      drug-induced steatohepatitis (DISH). METHODS: A language- and date-unrestricted
      Medline literature search was conducted to identify pertinent basic and clinical
      studies on the topic. RESULTS: Drugs can induce macrovesicular steatosis by
      mimicking NAFLD pathogenic factors, including insulin resistance and imbalance
      between fat gain and loss. Other forms of hepatic fat accumulation exist, such as
      microvesicular steatosis and phospholipidosis, and are mostly associated with
      acute mitochondrial dysfunction and defective lipophagy, respectively. Drug
      induced mitochondrial dysfunction is also commonly involved in DISH. Patients
      with pre-existing NAFLD may be at higher risk of DILI induced by certain drugs,
      and polypharmacy in obese individuals to treat their comorbidities may be a
      contributing factor. CONCLUSIONS: The relationship between DILI and NAFLD may be
      reciprocal: drugs can cause NAFLD by acting as steatogenic factors, and pre
      existing NAFLD could be a predisposing condition for certain drugs to cause DILI.
      Polypharmacy associated with obesity might potentiate the association between
      this condition and DILI.

PMID- 30194709
TI  - Comparison of catheter thrombogenicity in a modified chandler loop model using
      goat blood.
AB  - Thrombogenicity testing is a key component in the development of medical devices
      intended for contact with blood. The Chandler loop system has previously been
      used as an in vitro thrombogenicity testing method. In this study, we used a
      modified version of the Chandler loop model to evaluate its capacity to detect
      differential thrombogenic potential of different catheter materials using goat
      blood. We also sought to determine the optimal experimental conditions for
      detecting the thrombogenicity of catheter material. Using the Chandler loop
      system with goat blood we demonstrated that silicone catheters had a stronger
      thrombogenicity as compared to polyurethane catheters as evidenced by
      significantly larger thrombi (p < 0.001) and higher infusion pressures (p <
      0.05). This is consistent with many, but not all, previous in vitro and in vivo
      studies comparing polyurethane to silicone catheters. The use of this modified
      Chandler loop system with goat blood may provide an additional in vitro testing
      platform for thrombogenicity testing of catheters. (c) 2018 Wiley Periodicals,
      Inc. J Biomed Mater Res Part A: 106A: 3143-3151, 2018.

PMID- 30194710
TI  - Molecular layer deposition builds biocompatible substrates for epithelial cells.
AB  - The demand for novel biocompatible materials as surface coating in the field of
      regenerative medicine is high. We explored molecular layer deposition (MLD)
      technique for building surface coatings and introduced a new group of substrates
      consisting of amino acids, or nucleobases, and the biocompatible metal titanium.
      The substrates were built from titanium tetraisopropoxide (TTIP) with l-lysine,
      glycine, l-aspartic acid, l-arginine, thymine, uracil, and adenine. Substrates
      based on zirconium chloride and terephthalic acid were also included. Titanium
      oxide (TiO2 ) substrates made by atomic layer deposition and uncoated cover slips
      served as controls. Rat conjunctival epithelial goblet cells were grown in RPMI
      1640 and RT-PCR, immunofluorescence, cell attachment, proliferation, and
      viability were analyzed. Cells cultured on MLD and uncoated substrates were
      proliferating (positive for Ki67). Cell attachment after 3 h of culture on MLD
      substrates was similar to uncoated coverslips (p > 0.05). Compared to uncoated
      coverslips, cell proliferation assayed with alamarBlue(r) after 4 days was
      significantly higher on all MLD substrates (p < 0.05), whereas terephthalic acid
      containing MLD substrates reduced proliferation (p < 0.01). Viability assessed by
      LIVE/DEAD(r) was high (>85%) for all substrates after 5 days. The novel MLD
      technique is promising for building biocompatible substrates that direct
      epithelial cell growth. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part
      A: 106A: 3090-3098, 2018.

PMID- 30194711
TI  - Can synthetic urine replace authentic urine to "beat" workplace drug testing?
AB  - Synthetic urine (SU), which was primarily utilized by drug testing laboratories
      as a matrix for quality control preparations, is now commercially sold and can be
      used to "fool" a positive drug test. To determine if SU can pass as authentic
      urine, we challenged Army urine drug testing specimen accessioning and testing
      procedures using eight different commercial SU products. Adulteration (Sciteck
      AdultaCheck(r) 6) and Onsite SU (Synthetic UrineCheckTM) test strips were also
      evaluated. Five of the eight SU were identified by physical observation. All SU
      products screened negative in the drug immunoassay and additionally passed the
      specimen validity testing (SVT) as authentic urine. Furthermore, SU was not
      detected as adulterated with the adulteration test strips (Sciteck AdultaCheck(r)
      6) but was successfully detected as SU with the On-site synthetic urine
      (Synthetic UrineCheckTM). To deter SU use, direct observation, as utilized by the
      military, may be recommended during the collection process.

PMID- 30194712
TI  - Polyphyllin I Inhibits Proliferation and Induces Apoptosis by Downregulating AML1
      ETO and Suppressing C-KIT/Akt Signaling in t(8;21) Acute Myeloid Leukemia.
AB  - Polyphyllin I (PPI), a bioactive constituent extracted from traditional medicinal
      herbs, is cytotoxic to several cancer types. However, whether PPI can be used to
      treat t(8;21) acute myeloid leukemia (AML) cells requires further investigation.
      Here, we determined the inhibitory effects of PPI on t(8;21) AML cells by Cell
      Counting Kit-8 (CCK-8) and the trypan blue dye exclusion assay. DAPI staining and
      Wright-Giemsa staining were performed to check for apoptosis. Detection of
      apoptotic protein and AML1-ETO signaling protein expression were conducted by
      Western blot analysis. Our results suggested that PPI decreased growth and
      induced apoptosis in a dosage-dependent manner in the t(8;21) AML cell line
      Kasumi-1. PPI significantly downregulated AML1-ETO expression in a dosage- and
      time-dependent manner. PPI also upregulated P21 and downregulated survivin
      expression by reducing AML1-ETO. Mechanistically, PPI significantly reduced the
      expression of C-KIT, another therapeutic target for AML with t(8;21), followed by
      inhibition of Akt signaling. These results suggest that PPI can suppress growth
      and induce apoptosis of t(8;21) AML by suppressing the AML1-ETO and C-KIT/Akt
      signaling pathways. Therefore, PPI may be an anticancer therapeutic to treat
      t(8;21) AML.

PMID- 30194713
TI  - A novel strategy for evaluation of natural products acting on the
      myeloperoxidase/hypochlorous acid system by combining high-performance liquid
      chromatography-photodiode array detection-chemiluminescence and ultrafiltration
      mass spectrometry techniques.
AB  - Myeloperoxidase and its product hypochlorous acid are endogenous substances that
      are involved in the pathogenesis of many inflammatory diseases. In the present
      study, a novel evaluation strategy has been developed to screen for
      myeloperoxidase inhibitors and hypochlorous acid scavengers in natural products.
      The evaluation strategy uses two methods: a multi-hyphenated high-performance
      liquid chromatography-photodiode array detection-chemiluminescence online method,
      and an ultrafiltration-high-performance liquid chromatography-mass spectrometry
      method. Both were used for screening hypochlorous acid scavengers and
      myeloperoxidase inhibitors. After optimization of operating conditions, including
      pH of mobile phase and concentrations of myeloperoxidase, hypochlorous acid and
      luminol, the evaluation strategy was applied to Gardenia jasminoides Ellis
      (Rubiaceae) extract. Gardenia jasminoides Ellis (Rubiaceae) extract was found to
      both scavenge hypochlorous acid and inhibit myeloperoxidase. These different
      bioactivities originate from iridoid glycosides and quinic acid derivatives (25
      hypochlorous acid scavengers) and crocetin derivatives (4 myeloperoxidase
      inhibitors). In a mouse model of acute lung injury, pulmonary histopathology
      showed that different constituents of Gardenia jasminoides Ellis (Rubiaceae)
      extract could also attenuate lung injury. Although the screening strategy has two
      arms, it is still simple, rapid, and effective. The strategy can also potentially
      be used to discriminate different activities of different constituents contained
      in the same natural product.

PMID- 30194714
TI  - Structural basis for the pathogenesis of Campylobacter jejuni Hcp1, a structural
      and effector protein of the Type VI Secretion System.
AB  - The Type VI Secretion System (T6SS) provides enhanced virulence to Campylobacter
      jejuni and has been associated with a high incidence of bloody diarrhea. The
      hemolysin-coregulated protein (Hcp)-the hallmark of the T6SS-can act as a
      structural and effector protein. Unlike other T6SS-harboring bacteria, which
      possess multiple Hcp proteins each performing different functions, C. jejuni
      possesses only one Hcp protein, and its structural and functional role has not
      been elucidated previously. Here, we report the structure and functional studies
      of Hcp from C. jejuni. We found similarities between the hexameric ring structure
      of Hcp-Cj and that of Hcp3 from Pseudomonas aeruginosa. Through functional
      studies, we showed two roles for Hcp-Cj that is, in cytotoxicity toward HepG2
      cells and in biofilm formation in C. jejuni. In structure-based mutational
      analyses, we showed that an Arg-to-Ala mutation at position 30 within the
      extended loop results in a significant decrease in cytotoxicity, suggesting a
      role for this loop in binding to the host cell. However, this mutation does not
      affect its biofilm formation function. Collectively, this study supports the dual
      role of Hcp-Cj as a structural and effector protein in C. jejuni.

PMID- 30194716
TI  - Multifunctional antioxidant nanoliposome-mediated delivery of PTEN plasmids
      restore the expression of tumor suppressor protein and induce apoptosis in
      prostate cancer cells.
AB  - Prostate cancer is the second leading cause of cancer death in men and about one
      in nine will be diagnosed in his lifetime. Loss of PTEN has been considered as
      one of the major factors leading to the origin of prostate cancer through
      modulating PI3K/AKT signaling pathways. In this study, we have prepared a
      multifunctional antioxidant nanoliposome containing PTEN plasmid and cerium oxide
      nanoparticles (CeNPs). The efficient delivery of PTEN plasmid to human prostate
      cancer cells (PC-3) leads to restoration of the expression of lost PTEN protein
      in the cell cytoplasm. The delivered superoxide dismutase (SOD)-mimetic CeNPs
      were also found to decrease the cytoplasmic free radical levels in prostate
      cancer cells. The above two activities induced DNA fragmentation and micronucleus
      formation in prostate cancer cells. Furthermore, it was also found that these
      multifunctional antioxidant nanoliposomes inhibit the PI3K/AKT signaling pathway
      to negatively regulate the cell viability of prostate cancer cells. The mRNA
      expression pattern of other relevant proteins predominantly involved in cancer
      cell proliferation and apoptosis suggested that the high PTEN expression could
      control the synthesis of oncogenic proteins. (c) 2018 Wiley Periodicals, Inc. J
      Biomed Mater Res Part A: 106A: 3152-3164, 2018.

PMID- 30194715
TI  - Flow immunophenotyping of benign lymph nodes sampled by FNA: Representative with
      diagnostic pitfalls.
AB  - BACKGROUND: Fine-needle aspiration with flow cytometry (FNA-FC) is routinely used
      in the evaluation of lymph nodes suspicious for lymphoma, yet data comparing
      immunophenotype distributions and outliers in benign lymph nodes sampled by fine
      needle aspiration (FNA) versus excision are lacking. METHODS: Flow cytometry data
      from 289 benign lymph node FNA cases were assessed for the overall antigen
      distribution, with a focus on outliers relevant to the diagnosis of lymphoma.
      Distributions and outlier proportions were compared with those of a separate
      cohort of 298 excisional biopsies. RESULTS: Compared with excisional biopsies,
      FNA specimens overrepresented CD3+ events (72% vs 63%), underrepresented CD19+
      events (22% vs 29%), and had 25% fewer large cell-gated events. Normalized
      antigen distributions in FNA were equivalent to those in excisional biopsy.
      Twenty-three percent of FNA-FC cases exhibited an outlier, including a skewed
      kappa:lambda light-chain ratio, increased CD5+ or CD10+ B-cell events, a skewed
      CD4:CD8 ratio, and increased CD7 loss on T cells, with no significant differences
      in frequency or type in comparison with excisional specimens. Outliers for the
      light-chain ratio and T-cell antigens were enriched among older patients and
      included patients with a variety of autoimmune/rheumatologic conditions.
      CONCLUSIONS: Benign lymph node FNA yields flow immunophenotypes remarkably
      similar to those from excisional biopsies. Outlier flow immunophenotypes are
      identified in benign lymph nodes sampled by FNA at a frequency similar to that
      with excisional biopsies. Older patients, who have a higher baseline risk of
      lymphoma, are more likely to exhibit lymphoma-mimicking outliers such as a light
      chain predominance on B cells and skewed CD4:CD8 ratios or increased CD7 loss on
      T cells, and they warrant additional diagnostic caution.

PMID- 30194717
TI  - Preparative and capillary isoelectric focusing for detection and identification
      of Aspergillus conidia in complex sample matrices.
AB  - This study describes a new method for fast identification of highly hydrophobic
      conidia of Aspergillus species from both simple and complex matrices. The method
      is based on recently developed preparative isoelectric focusing in a cellulose
      based separation medium which had to be modified with respect to the highly
      hydrophobic surface of the conidia. Although Aspergillus conidia are colored,
      their zones in the cellulose bed were indicated by colored isoelectric point
      markers. The isoelectric point values of Aspergillus conidia were determined by
      capillary isoelectric focusing. Preparative isoelectric focusing was successfully
      used for preconcentration of individual conidia of cultivated strains of
      Aspergillus niger, Aspergillus fumigatus, Aspergillus flavus, and Aspergillus
      parasiticus, and also for separation of the conidia in a mixture. Subsequently,
      red pepper powder and peanuts spiked with Aspergillus niger and Aspergillus
      flavus conidia, respectively, were used as complex matrices. The detection limit
      for identification of the conidia in these complex matrices is 104 conidia mL-1 .
      The presence of conidia in the focused zones was confirmed by their subsequent
      analysis by capillary isoelectric focusing. Their viability was confirmed by a
      cultivation of the conidia extracted from the collected fractions after
      preparative isoelectric focusing.

PMID- 30194719
TI  - Need for Migraine/Perimenopausal Research.

PMID- 30194718
TI  - Hirudin Protects Ang II-Induced Myocardial Fibroblasts Fibrosis by Inhibiting the
      Extracellular Signal-Regulated Kinase1/2 (ERK1/2) Pathway.
AB  - BACKGROUND Myocardial fibrosis is closely related to all types of cardiovascular
      diseases. Hirudin is widely used in the prevention and treatment of
      cardiovascular diseases and cancers. In this study, we examined the potential
      role(s) and mechanism of hirudin in angiotensin II (Ang II)-induced myocardial
      fibrosis. MATERIAL AND METHODS The viability of myocardial fibroblasts, and
      reactive oxygen species (ROS) rates were measured respectively using cell
      counting kit-8 (CCK-8) and flow cytometry. Malondialdehyde (MDA) content, the
      activities of lactate dehydrogenase (LDH), and superoxide dismutase (SOD) were
      detected by the respective kits. The mRNA and protein levels of fibrosis-related
      factors were separately assessed by qRT-PCR and western blot. RESULTS Our data
      revealed that hirudin suppressed the viability of myocardial fibroblasts, and
      that it relieved the proliferation induced by Ang II in a dose-dependent manner.
      We also found that hirudin reduced ROS production, LDH activity, and MDA content;
      however, it enhanced SOD activity. Moreover, while hirudin significantly
      downregulated the levels of matrix metalloproteinase-2 (MMP-2), MMP-9,
      fibronectin (FN), transforming growth factor beta 1 (TGF-beta1), collagen-I (COL
      I), and COL-III, it upregulated the expression level of tissue inhibitor of
      metalloproteinases-2 (TIMP-2). Furthermore, phosphorylated extracellular signal
      regulated kinase1/2 (p-ERK1/2) was decreased by hirudin, compared to the Ang-II
      group. CONCLUSIONS Hirudin depressed Ang II-induced myocardial fibroblasts via
      inhibiting oxidative stress, regulating fibrosis-related factors, and repressing
      the ERK1/2 pathway.

PMID- 30194720
TI  - Totally implantable active middle ear implant: Hearing and safety results in a
      large series.
AB  - OBJECTIVES: To evaluate hearing performance and safety measures in a large group
      of totally implantable active middle ear implant (AMEI) wearers. METHODS:
      Retrospective case review of 172 ears (166 patients) with sensorineural hearing
      loss undergoing implantation of a totally implantable AMEI. Pure-tone air and
      bone thresholds, pure-tone average, speech reception threshold (SRT), and word
      recognition scores (WRS) at phonetically balanced maximum and at 50 dB (WRS50)
      were assessed at baseline unaided, with a hearing aid (baseline aided [BLA]),
      with the implant at activation, and for best implant postoperative measurement.
      Adverse events were reviewed. RESULTS: Mean length of follow-up was 35.7 months.
      Compared to unaided, the implant provided significant gain at all frequencies
      through 6 kHz. Amount of gain was significantly better with the implant than BLA
      at 1,500 and 2,000 Hz (P <= .001). Implant SRT was also significantly improved
      compared to BLA (29.9 dB vs. 38.5 dB, P <= .001). At a 50-dB presentation level,
      WRS was significantly better with the implant than BLA (65.6% vs. 45.5%, P <=
      .001). Bone conduction thresholds were not affected by the implant. The most
      common adverse event was taste disturbance, which occurred in 39.1%. In subjects
      with preimplant tinnitus, 56.1% experienced resolution of their tinnitus.
      Revision surgery was required in 15.7%, and 4% were ultimately explanted.
      CONCLUSION: The implant provided significant hearing benefit compared to unaided
      and to the subjects' own hearing aids in most test categories, with minimal
      adverse events. Many subjects experienced complete resolution of their tinnitus
      after implantation. LEVEL OF EVIDENCE: 4. Laryngoscope, 2018.

PMID- 30194721
TI  - Postoperative revisits and readmissions after facelift surgery.
AB  - OBJECTIVES/HYPOTHESIS: To determine 30-day rates and reasons for revisit and
      readmission after rhytidectomy surgery. STUDY DESIGN: Cross-sectional analysis.
      METHODS: Cross-sectional analysis was performed of multistate ambulatory surgery
      and hospital databases. Ambulatory rhytidectomy cases were extracted from State
      Ambulatory Surgery Databases for New York, Florida, Iowa, and California for 2010
      and 2011. Cases were linked to State Emergency Department and Inpatient Databases
      for visits occurring 1 to 30 days postoperatively. RESULTS: A total of 6,089
      rhytidectomy cases were extracted (87.9% female). The mean age was 61.1 years,
      and the most common age group was 61 to 70 years (40.2%), followed by 51 to 60
      years (33.2%), and 71 to 80 years (12.0%). Overall, 3.6% of patients had a
      revisit after surgery (42.7% to an ambulatory surgery center, 42.2% to an
      emergency department, and 15.1% to inpatient admission). The most common primary
      diagnoses at the time of the revisit were hematoma (17.0%), fever/nausea/diarrhea
      (4.1%), and urinary tract infection (4.1%). CONCLUSIONS: Rhytidectomy is
      performed to treat facial aging, and can provide surgical outcomes which may not
      be achievable with nonsurgical alternatives. The 30-day revisit and readmission
      rate for this procedure in a large multistate cohort has not previously been
      reported. The revisit rate is low after rhytidectomy, and the most common reason
      for revisit is hematoma. These data provide important insight to optimize
      perioperative management and decrease postoperative revisits. This study does not
      capture return visits to the physician's office; however, postoperative issues
      that require presentation to outside facilities are important to distinguish from
      those managed in the practitioner's office, because they may incur additional,
      unplanned cost to both the patient and the healthcare system. LEVEL OF EVIDENCE:
      NA. Laryngoscope, 2018.

PMID- 30194722
TI  - Human laryngeal sensory receptor mapping illuminates the mechanisms of laryngeal
      adductor reflex control.
AB  - OBJECTIVE: The laryngeal adductor reflex (LAR) is an airway protective response
      triggered by sensory laryngeal receptors. It is unknown whether different glottic
      and supraglottic subsites vary in their reflex elicitation abilities. The recent
      discovery that a bilateral LAR is present in humans under general anesthesia upon
      laryngeal mucosal stimulation has enabled us to map the sensory receptor density
      for LAR elicitation at different laryngeal subsites. Our findings expose the
      likely mechanisms of LAR control. METHODS: Prospective series of 10 patients
      undergoing laryngoscopy. Laryngeal subsites (epiglottic tip, membranous vocal
      fold, midventricular vocal fold, posterior supraglottis, epiglottic petiole) were
      stimulated via direct laryngoscopy with a bipolar probe. Vocal fold responses
      were recorded by endotracheal tube and hook wire electrodes, and visual
      observation. RESULTS: Posterior supraglottic stimulation elicited bilateral LARs
      in all patients at all intensities. Membranous vocal folds, epiglottic petiole,
      and subglottis elicited no LAR. Ventricular fold and epiglottic tip responses
      converted from ipsi- to bilateral at high intensities. CONCLUSION: There are
      likely three checkpoints for control of the LAR in humans. These checkpoints
      protect against inappropriate LAR activation during volitional tasks without
      compromising airway protection: 1) topographical differences in receptor density
      with the highest density in subsites most likely to contact foreign substances;
      2) absence of receptors in membranous vocal folds; and 3) central summation
      threshold for crossed interneuron activation at brainstem level where only strong
      intensity stimuli will elicit bilateral responses. Checkpoint dysfunction
      provides a novel framework to diagnose and treat disease processes, including
      aspiration, laryngospasm, and sudden infant death. LEVEL OF EVIDENCE: 4.
      Laryngoscope, E365-E370, 2018.

PMID- 30194723
TI  - The role of chaperones in iron-sulfur cluster biogenesis.
AB  - Iron-sulfur cluster biogenesis is a complex process mediated by numerous proteins
      among which two from bacteria chaperones, called HscB and HscA in bacteria. They
      are highly conserved up to eukaryotes and homologous to DnaJ and DnaK,
      respectively, but with specific differences. As compared with other chaperones,
      HscB and HscA have escaped attention and relatively little is known about their
      functions. After briefly introducing the various chaperone families, we reviewed
      here the current structural and functional knowledge HscA and HscB and on their
      role in cluster formation. We critically evaluated the literature and highlighted
      the weak aspects which will require more attention in the future. We sincerely
      hope that this study will inspire new interest on this important and interesting
      system.

PMID- 30194724
TI  - Outcomes of 200 consecutive, fluoroless atrial fibrillation ablations using a new
      technique.
AB  - INTRODUCTION: A technique was developed to eliminate radiation exposure for
      routine atrial fibrillation (AF) ablation, to simplify the procedure and to
      achieve cost effectiveness. We here report the outcomes of this approach.
      METHODS: Two hundred consecutive AF ablations (55% paroxysmal) were performed by
      a single operator. Pulmonary vein isolation (PVI) was achieved by antral ablation
      without left atrial anatomic mapping, guided by contact force sensing and
      intracardiac echocardiogram (ICE). All ablations were performed using three
      ipsilateral 8 French catheters (ICE, Lasso, and ablation). Eighty-two percent of
      the patients underwent ablation of atrial flutter or non-pulmonary vein triggers.
      All patients underwent provocative testing after PVI. RESULTS: No fluoroscopy was
      used for the entire study. Two ablations were performed without x-ray available
      due to unexpected equipment failure. The mean procedure time was 90.3 +/- 17.7
      (minutes) in patients who only required PVI and 106.2 +/- 23.2 (minutes) for the
      entire cohort, with a success rate of 76% (mean follow-up of 11 months). In
      contrast, the procedure time and success rate were 127.9 +/- 38.2 (minutes) (P <
      0.01) and 74%, respectively, for the last 50 standard ablations guided by
      fluoroscopy (without contact force sensing). Complications included one case of
      partial right phrenic nerve palsy and one case of right femoral artery
      pesudoaneurysm. Compared to our previous ablation approaches, the new method
      resulted in catheter savings of $2,168-$4,568/case. CONCLUSION: The new technique
      eliminated radiation exposure and shortened the procedure time without
      significant negative impact on safety or success rate. Substantial cost savings
      were also achieved by using a minimal number of mostly reprocessed catheters.

PMID- 30194725
TI  - Tripeptide binding in a proton-dependent oligopeptide transporter.
AB  - Proton-dependent oligopeptide transporters (POTs) are important for the uptake of
      di-/tripeptides in many organisms and for drug transport in humans. The binding
      mode of dipeptides has been well described. However, it is still debated how
      tripeptides are recognized. Here, we show that tripeptides of the sequence Phe
      Ala-Xxx bind with similar affinities as dipeptides to the POT transporter from
      Streptococcus thermophilus (PepTS t ). We furthermore determined a 2.3-A
      structure of PepTS t in complex with Phe-Ala-Gln. The phenylalanine and alanine
      residues of the peptide adopt the same positions as previously observed for the
      Phe-Ala dipeptide, while the glutamine side chain extends into a hitherto
      uncharacterized pocket. This pocket is adaptable in size and can likely
      accommodate a wide variety of peptide side chains.

PMID- 30194726
TI  - The Effect of Sedating Agents on Drug-Induced Sleep Endoscopy Findings.
AB  - OBJECTIVE: Drug-induced sleep endoscopy (DISE) has gained interest for upper
      airway evaluation in patients with snoring and obstructive sleep apnea (OSA), and
      different drugs have been used to induce sedation. Nevertheless, all drugs have
      presented specific advantages and disadvantages with differential effects on
      respiratory physiology. This study evaluated and compared the effects of
      midazolam, propofol and dexmedetomidine on DISE findings, O2 nadir, and
      bispectral index (BIS) in the same sample of patients. STUDY DESIGN: Case series
      prospective study. METHODS: Consecutive patients who elected to undergo surgery
      for OSA treatment and were intolerant to conservative therapies underwent DISE
      with propofol, dexmedetomidine, and midazolam between July 2015 and July 2016.
      RESULTS: Fifty-two patients were analyzed, and 43 (82.7%) were men. Agreement
      among drugs for both degree and patterns of obstruction was excellent at all
      sites (velum, oropharynx, and epiglottis) except for the tongue base.
      Dexmedetomidine had the least complete collapse sites and highest O2 nadir and
      was the only drug for which apnea severity and obstruction levels (upper, lower,
      or combined) were correlated. The variability among drug treatments for the BIS
      index was considerable, and propofol had the lowest variability and average
      value. CONCLUSION: Drug selection had a relevant influence in DISE findings.
      Compared with dexmedetomidine, midazolam and propofol presented higher incidence
      of tongue base collapse, lower O2 levels, and lower BIS index values. Propofol
      resulted in an O2 nadir that most resembled that observed during polysomnography.
      The BIS index variability differed among drugs, and its use was considered
      relevant for sedation orientation. LEVEL OF EVIDENCE: 4. Laryngoscope, 2018.

PMID- 30194728
TI  - Epidemiology of Merkel cell carcinoma. A population-based study from 1985 to
      2013, in northeastern of France.
AB  - Merkel Cell Carcinoma (MCC) is an aggressive skin cancer with an increasing
      incidence. Population-based epidemiologic data about MCC in France are rare. Our
      study aims to describe the epidemiology of MCC in Bas-Rhin, Northeastern of
      France, between 1985 and 2013. Data were collected from the Bas-Rhin Cancer
      Registry. We measured age-adjusted incidence rates (per 100,000 person-years) and
      effect of age, sex and period of diagnosis on survival. The world age
      standardized incidence rate was 0.17 and it quadrupled between 1985 and 2013.
      Cases (n = 111) occurred mostly in women (60%) and in persons >=70 years of age
      (74%). Incidence rates was close for men (0.18) and women (0.16) and was 25-time
      higher in people >=70 years of age but incidence rate similarly increased between
      1985 and 2013 in persons older and younger than 70 years. Net 5-year survival was
      48.5%; female sex and younger age were positive predictors of survival. Given the
      low number of cases, incidence and survival data should be interpreted with
      caution. Incidence of MCC in Bas-Rhin quadrupled between 1985 and 2013. The
      highest incidence rate was observed in people >=70 years. Better survival was
      associated with female sex and younger age. We hypothesize that MCC will still
      increase and be diagnosed in increasingly younger patients in next generations.

PMID- 30194727
TI  - Skeletal muscle ceramides and relationship with insulin sensitivity after 2 weeks
      of simulated sedentary behaviour and recovery in healthy older adults.
AB  - KEY POINTS: Insulin sensitivity (as determined by a hyperinsulinaemic-euglyceamic
      clamp) decreased 15% after reduced activity. Despite not fully returning to
      baseline physical activity levels, insulin sensitivity unexpectedly, rebounded
      above that recorded before 2 weeks of reduced physical activity by 14% after the
      recovery period. Changes in insulin sensitivity in response to reduced activity
      were primarily driven by men but, not women. There were modest changes in
      ceramides (nuclear/myofibrillar fraction and serum) following reduced activity
      and recovery but, in the absence of major changes to body composition (i.e. fat
      mass), ceramides were not related to changes in inactivity-induced insulin
      sensitivity in healthy older adults. ABSTRACT: Older adults are at risk of
      physical inactivity as they encounter debilitating life events. It is not known
      how insulin sensitivity is affected by modest short-term physical inactivity and
      recovery in healthy older adults, nor how insulin sensitivity is related to
      changes in serum and muscle ceramide content. Healthy older adults (aged 64-82
      years, five females, seven males) were assessed before (PRE), after 2 weeks of
      reduced physical activity (RA) and following 2 weeks of recovery (REC). Insulin
      sensitivity (hyperinsulinaemic-euglyceamic clamp), lean mass, muscle function,
      skeletal muscle subfraction, fibre-specific, and serum ceramide content and
      indices of skeletal muscle inflammation were assessed. Insulin sensitivity
      decreased by 15 +/- 6% at RA (driven by men) but rebounded above PRE by 14 +/- 5%
      at REC. Mid-plantar flexor muscle area and leg strength decreased with RA,
      although only muscle size returned to baseline levels following REC. Body fat did
      not change and only minimal changes in muscle inflammation were noted across the
      intervention. Serum and intramuscular ceramides (nuclear/myofibrillar fraction)
      were modestly increased at RA and REC. However, ceramides were not related to
      changes in inactivity-induced insulin sensitivity in healthy older adults. Short
      term inactivity induced insulin resistance in older adults in the absence of
      significant changes in body composition (i.e. fat mass) are not related to
      changes in ceramides.

PMID- 30194729
TI  - Activation of the innate immune system is evident throughout epileptogenesis and
      is associated with blood-brain barrier dysfunction and seizure progression.
AB  - OBJECTIVE: Because brain inflammation may contribute to the pathophysiology of
      temporal lobe epilepsy (TLE), we investigated the expression of various
      inflammatory markers of the innate and adaptive immune system in the
      epileptogenic human and rat hippocampus in relation to seizure activity and blood
      brain barrier (BBB) dysfunction. METHODS: Immunohistochemistry was performed
      using various immune cell markers (for microglia, monocytes, macrophages, T
      lymphocytes, and dendritic cells) on hippocampal sections of drug-resistant TLE
      patients and patients who died after status epilepticus. The expression of these
      markers was also studied in the electrical post-status epilepticus rat model for
      TLE, during the acute, latent, and chronic epileptic phase. BBB dysfunction was
      assessed using albumin immunohistochemistry and the BBB tracer fluorescein.
      RESULTS: Monocyte infiltration, microglia, and perivascular macrophage activation
      were persistently increased in both epileptogenic human and rat hippocampus,
      whereas T lymphocytes and dendritic cells were not or were scarcely detected. In
      addition to this, increased expression of C-C motif ligand 2 (CCL2) and
      osteopontin was observed. In humans, the expression of CD68 and CCL2 was related
      to the duration of epilepsy and type of pathology. In rats, the expression of
      CD68, CCL2, and the perivascular macrophage marker CD163 was related to the
      duration of the initial insult and to the number of spontaneous seizures.
      Interestingly, the number of CD163-positive perivascular macrophages was also
      positively correlated to BBB dysfunction in chronic epileptic rats. SIGNIFICANCE:
      These data suggest a proepileptogenic role for monocytes/macrophages and other
      cells of the innate immune response, possibly via increased BBB leakage, and
      indicate that T cells and dendritic cells, which are closely associated with the
      adaptive immune response, are only sparsely infiltrated during epileptogenesis in
      the electrical post-status epilepticus rat model. Future studies should reveal
      the relative importance of these immune cells and whether specific manipulation
      can modify or prevent epileptogenesis.

PMID- 30194730
TI  - Irradiated ears in nasopharyngeal carcinoma survivors: A review.
AB  - This article reviews the literature on otological complications in nasopharyngeal
      carcinoma (NPC) survivals after irradiation during the past three decades.
      Symptoms of the irradiated ears were assessed from the external ear canal,
      through the middle ear cavity including the Eustachian tube, and to the inner ear
      compartments. The development of radioimaging diagnostic techniques, the
      introduction from adjuvant chemotherapy to concurrent chemoradiotherapy, and the
      invention of radiotherapeutic equipment to intensity-modulated radiotherapy
      (IMRT) have increased the survival rate of NPC patients during the past 30 years.
      The prevalence of cochlear and vestibular deficits has decreased a lot, whereas
      middle ear complications (i.e., otitis media with effusion and radiation-induced
      otitis media) do not decline in NPC survivors even in the IMRT era, probably
      because the medial half of the Eustachian tube receives > 95% of the total dose
      despite 2DRT or IMRT. Laryngoscope, 2018.

PMID- 30194731
TI  - Clinical use of the STOP-BANG questionnaire to determine postoperative risk in
      veterans.
AB  - OBJECTIVES: To determine whether STOP-BANG (snoring, tiredness, observed apnea,
      high blood pressure, body mass index, age, neck circumference, gender) scores are
      associated with immediate postoperative adverse events in veterans undergoing
      surgery. METHODS: In this prospective cohort study, veterans presenting to the
      presurgical clinic at a Veterans Affairs hospital answered the STOP-BANG
      questionnaire, which was scored as high risk (5-8), intermediate risk (3-4), and
      low risk (0-2) for obstructive sleep apnea (OSA), during a 6-month study period.
      Immediate postoperative respiratory and cardiovascular adverse events were
      recorded. RESULTS: The patient population included 1,080 veterans. Ninety-five
      patients (8.8%) experienced adverse events, of which 74 (6.9%) were respiratory
      and 21 (1.9%) were cardiovascular in nature. Patients with high-risk STOP-BANG
      scores (5-8) had significantly greater odds of having an adverse event odds ratio
      (OR) 2.1 (95% confidence interval [CI]: 1.4, 3.3) and hypoxia OR 2.8 (95% CI:
      1.7, 4.6) compared to those with low- to intermediate-risk scores (0-4). Among
      patients with OSA, those with high-risk scores (5-8) had greater odds of an
      adverse event OR 3.9 (95% CI: 1.1, 13.9) and hypoxia OR 3.7 (95% CI: 1.1, 13.0)
      compared to those with low- to intermediate-risk scores (0-4). Patients without a
      history of OSA with high-risk scores (5-8) did not have significantly greater
      odds of an adverse event OR 1.5 (95% CI: 0.82, 2.6) or a hypoxic event OR 1.7
      (95% CI: 0.87, 3.4) compared to those with low- to intermediate-risk scores (0
      4). CONCLUSION: The STOP-BANG questionnaire was useful in the veteran population
      because high-risk scores were predictive of adverse events, in particular,
      hypoxia for patients with a previous diagnosis of OSA. In the future, this may
      direct studies and clinical activities aimed at optimizing safe and effective
      perioperative practices. LEVEL OF EVIDENCE: 2b. Laryngoscope, 2018.

PMID- 30194732
TI  - Clinical and Economic Impact of Time From Admission for CSF Rhinorrhea to
      Surgical Repair.
AB  - BACKGROUND: If conservative management of CSF leak is unsuccessful, surgical
      repair is indicated for the prevention of severe complications such as
      meningitis. This study investigated the influence of surgical timing on clinical
      and economic outcomes. METHODS: Retrospective review of the National Inpatient
      Sample (2012) and the Nationwide Inpatient Sample (2002-2011) for nonelective
      admissions with a principal diagnosis of CSF rhinorrhea treated with surgical
      repair of the meninges. Demographics and outcomes of patients undergoing
      meningeal repair for CSF rhinorrhea were analyzed. Cases were classified into
      four groups based on timing of surgical intervention: 1) performed on the day of
      admission (day 0), 2) performed between days 1 and 3, 3) performed between days 4
      and 7, and 4) performed between days 8 and 14. RESULTS: A total of 1,088 emergent
      admissions were analyzed. On average, patients underwent surgical repair between
      the second and fourth day of admission. Lowest rates of meningitis were in
      patients treated on the day of admission (6.1%); those treated at 2 weeks had a
      34.7% incidence. Multivariate analysis controlling for comorbidity burden,
      gender, and surgical timing found the highest odds of meningitis in patients
      treated with surgical repair during the second week of admission compared to
      repair on the day of admission (OR 8.2, P < .001). Length of stay (LOS) and
      hospital costs increased as time to repair increased. CONCLUSION: Multiple
      factors influence outcomes in patients with CSF rhinorrhea. Early surgical repair
      was significantly associated with decreased rates of meningitis, LOS, and
      hospital costs. Expedient treatment of patients admitted for CSF rhinorrhea may
      prove to be both a cost- and morbidity-saving measure. LEVEL OF EVIDENCE: 2c.
      Laryngoscope, 2018.

PMID- 30194733
TI  - Social isolation alters ultrasonic vocalizations but not thyroarytenoid
      neuromuscular junctions in old rats.
AB  - OBJECTIVE: Age-related muscle atrophy of the laryngeal muscles contributes to
      presbyphonia. Remodeling of the neuromuscular junction is one aspect underlying
      age-related muscle atrophy. Although muscle disuse has been shown to exacerbate
      age-related neuromuscular changes in the limb muscles, it is unknown if reduced
      vocal use has a similar effect in the laryngeal muscles. The objective of this
      study was to examine the use of social isolation as a novel method to reduce
      vocal use in old rats-and the impact of that reduced vocal use on ultrasonic
      vocalization acoustics and neuromuscular junction morphology in the
      thyroarytenoid muscle. STUDY DESIGN: Animal group comparison. METHODS: Old
      F344/BN rats (31 months of age) were socially isolated (n = 8) or communally
      housed (n = 8) for 8 weeks. Effect of housing condition on ultrasonic
      vocalization acoustics was assessed by calculating the changes in vocalization
      fundamental frequency and amplitude from baseline to 8 weeks. Neuromuscular
      junction morphology was measured in the lateral and medial portions of the
      thyroarytenoid muscle at the conclusion of the experiment. RESULTS: Vocalization
      amplitude decreased by a mean of -4.4 dB (standard deviation [SD], 4.49) after
      social isolation, whereas amplitude increased by a mean of 5.7 dB (SD, 5.07) in
      the communally housed rats (P = 0.002). There was no significant difference in
      the change in fundamental frequency between groups. Furthermore, there were no
      group differences in any measure of neuromuscular junction morphology.
      CONCLUSION: These results suggest that neuromuscular junctions in the
      thyroarytenoid muscle of old rats are unaffected by 8 weeks of social isolation,
      despite functional changes in vocalizations. LEVEL OF EVIDENCE: NA. Laryngoscope,
      2018.

PMID- 30194734
TI  - Unearthing a consistent bilateral R1 component of the laryngeal adductor reflex
      in awake humans.
AB  - OBJECTIVE: The laryngeal adductor reflex (LAR) is an essential tracheobronchial
      protective mechanism resulting in vocal fold adduction to laryngeal stimulation.
      It was thought to consist of an early ipsilateral R1 component and a later,
      bilateral but highly centrally modulated R2 component. We recently demonstrated
      that bilateral R1 responses are robustly present in humans under general
      anesthesia. We herein give evidence that the R1 response is also bilateral in
      awake humans and is likely the primary component responsible for initiating the
      LAR. METHODS: Seven volunteers were included (3 males, 4 females). The reflex was
      elicited by direct percutaneous monopolar needle stimulation of the internal
      superior laryngeal nerve. Electromyography traces from bilateral lateral
      cricoarytenoid muscles were recorded using hookwire electrodes. Reflex responses
      to variations in stimulus intensity and duration were evaluated. RESULTS:
      Bilateral R1 responses were recorded in all patients, even during deep
      inspiration when the vocal folds were maximally abducted. R1, but not R2,
      responses increased linearly in amplitude, with sequential increases in both
      stimulation intensity (1-8 mA) and duration (100-500 usec) (Pearson correlation
      0.94). CONCLUSION: Contradicting over 40 years of research, we demonstrate that
      the R1 LAR component is consistently bilateral in awake humans. It increases
      linearly with stimulus intensity and is unaffected by conscious state suggesting
      minimal central control. These findings may provide a means to objectively
      stratify patients for risk of laryngeal aspiration, even in unconscious states,
      and its potentially cardinal role in disease states such as laryngospasm and
      sudden infant death needs to be reevaluated. LEVEL OF EVIDENCE: 4. Laryngoscope,
      2581-2587, 2018.

PMID- 30194735
TI  - Extended high-frequency hearing loss following the first episode of otitis media.
AB  - OBJECTIVES/HYPOTHESIS: Otitis media has been associated with several auditory and
      developmental sequelae. Here, the results of auditory tests were evaluated in
      patients who had a first episode of unilateral otitis media and compared with the
      contralateral healthy ear. STUDY DESIGN: Cohort study. METHODS: This study was
      undertaken from 2015 to 2016, with a follow-up period of 6 months. RESULTS: A
      total of 41 patients who had been diagnosed with unilateral acute otitis media
      were selected. Standard (250 Hz-8 kHz) and extended high-frequency (8 kHz-16 kHz)
      audiometry was performed within 5 days of the beginning of the clinical symptoms,
      and then in defined time frames for a period of 6 months. The results of the
      contralateral healthy ears were used as individual controls. After closure of the
      initial air-bone gap, the results of the standard audiometry did not demonstrate
      significant differences in the thresholds of diseased ears compared with
      controls. A significant elevation of the mean extended high-frequency thresholds
      in the ears affected by otitis media was observed at the first and subsequent
      appointments within the 6-month follow-up period. Diseased ears from patients who
      experienced tinnitus during the 6-month follow-up period had significantly higher
      thresholds in the extended high frequencies than diseased ears from patients
      without residual tinnitus. CONCLUSIONS: These results suggest that the first
      episode of otitis media may lead to persistent elevation of the mean thresholds
      of extended high-frequencies, whereas persistent tinnitus after 6 months of the
      acute infection is associated with more severe hearing loss. LEVEL OF EVIDENCE:
      2b Laryngoscope, 2018.

PMID- 30194736
TI  - Pathophysiology of sensorineural hearing loss in jugular foramen paraganglioma.
AB  - OBJECTIVES/HYPOTHESIS: Pathologic involvement of the inferior cochlear vein is a
      mechanism of sensorineural hearing loss in patients with jugular foramen
      paraganglioma. STUDY DESIGN: Retrospective case-control study. METHODS: The
      presenting audiograms, magnetic resonance imaging, and computed tomography were
      reviewed in 46 subjects with jugular foramen paragangliomas. Four-frequency bone
      conduction average was compared between the tumor and nontumor ears in each
      subject to establish the presence of sensorineural hearing loss. Imaging findings
      for each subject were recorded. Univariate and multivariate statistical analyses
      were performed to determine which radiographic features were associated with
      sensorineural hearing loss. Hearing data were analyzed as a continuous variable
      and as a categorical variable. RESULTS: Twenty subjects (43.4%) had a bone
      conduction pure-tone asymmetry of greater than 15 dB. Inferior cochlear vein
      involvement was identified in 19 of the 20 (95%) subjects with sensorineural
      hearing loss. Inferior cochlear vein involvement was found to be a statistically
      significant predictor of sensorineural hearing loss using univariate and
      multivariate analyses. Other imaging findings that were statistically significant
      predictors of sensorineural hearing loss include Glasscock-Jackson stage, Fisch
      Mattox stage, hypoglossal canal involvement, jugulo-carotid spin erosion, and
      petrous carotid canal erosion. CONCLUSIONS: Involvement of the inferior cochlear
      vein appears to be a plausible mechanism for sensorineural hearing loss in
      patients with jugular foramen paraganglioma. LEVEL OF EVIDENCE: 4 Laryngoscope,
      2018.

PMID- 30194738
TI  - Radiographic bone loss and the risk of medication-related osteonecrosis of the
      jaw (MRONJ) in multiple myeloma patients-A retrospective case control study.
AB  - Risk factors for medication-related osteonecrosis of the jaws (MRONJ) include
      type and duration of antiresorptive drugs, dental trauma, local anatomy, systemic
      underlying conditions and therapy, smoking, and the presence of periodontal
      disease. However, there is a lack of studies elucidating the role of periodontal
      disease as risk predictor. In the present study, the dental charts of 100
      multiple myeloma (MM) patients and 16 MM patients who developed MRONJ were
      studied. Information about age, gender, smoking history, diabetes, steroid drug
      intake, type and duration of bisphosphonate (BP) treatments, MRONJ status,
      missing teeth, periapical lesions, widening of the periodontal ligament, and
      periodontal status was collected. The periodontal status was determined as a
      percentage of missing bone at the mesial and distal surfaces of each tooth.
      Multivariable logistic regression was performed to identify risk factors
      associated with MRONJ. In the selected model, using the COX analysis, categorical
      bone loss percentage is significantly associated with MRONJ (P = 0.009), with
      hazard ratio 0.042 (high vs low) and 95% CI 0.004 to 0.453. Gender, steroid,
      Aredia BP type, and periapical are also significant in selected model. In
      conclusion, advanced alveolar bone loss and missing teeth were strongly related
      to the occurrence of MRONJ in MM patients.

PMID- 30194737
TI  - Iowa nursing facility oral hygiene (INFOH) intervention: A clinical and
      microbiological pilot randomized trial.
AB  - PURPOSE/AIM: The aim of this pilot study was to evaluate feasibility and gather
      initial data for a definitive study to test the clinical and microbiological
      effectiveness of a nursing facility (NF) customized oral hygiene protocol,
      intended to be delivered by dental hygienists and NF personnel. MATERIALS AND
      METHODS: A convenience sample of 8 Eastern Iowa NFs was recruited, and each NF
      was assigned to one of three intervention groups: (1) control (current oral
      hygiene practice), (2) educational program only, and (3) educational program plus
      1% chlorhexidine varnish monthly application. Demographic information, systemic
      health data, patient centered data, oral health data, and microbiology samples
      were collected at baseline and after 6 months. RESULTS: Recruitment response
      rates were 21% for NFs and 23% for residents. A total of 81 residents were
      examined at baseline and of those, 49 were examined at 6 months (39.5%
      attrition). There were no statistically or clinically significant differences
      among the intervention groups at 6 months for any of the recorded clinical or
      microbiological outcomes. CONCLUSIONS: Recruitment and retention posed a
      significant challenge to this trial, even with a relatively short observation
      period. Results from this pilot study did not encourage further investigation of
      this customized oral hygiene protocol.

PMID- 30194740
TI  - Allometric scaling of morphology and engulfment capacity in rorqual whales.
AB  - Body length is one of the most important factors that influence organismal
      function and ecological niche. Although larger animals tend to have a suite of
      physiological advantages, such as lower mass-specific metabolic rates and lower
      costs of transport, they may also experience significant limitations to unsteady
      locomotor performance or maneuverability because of the relative scaling of
      control surface areas and body mass. Rorqual whales are the largest of all
      animals and thus represent a unique study system for understanding how animals
      function at the extreme of body mass. Rorquals are characterized by an engulfment
      filtration foraging strategy facilitated by a complex set of morphological
      adaptations. We studied the scaling of key morphological structures related to
      locomotion and feeding in six rorqual species in a comparative framework. Our
      analyses show that most rorqual species exhibit positive allometry of both the
      control surfaces and body length, but the large scaling differences between these
      parameters suggest that larger rorquals will predictably suffer from decreased
      maneuverability and unsteady locomotor performance. However, we found that the
      dimensions of the engulfment apparatus also exhibit positive allometry, and thus
      engulfment capacity was relatively greater in larger rorquals. We posit that the
      allometric growth in the engulfment apparatus may be an adaptation that
      ameliorates the detrimental effects of large size on maneuverability. Our
      analyses also reveal significant differences in the scaling of mass-specific
      engulfment capacity among rorqual species that may reflect the evolution of
      unique foraging behaviors and the exploitation of divergent ecological niches.

PMID- 30194739
TI  - A Novel Model to Predict 1-Month Risk of Transplant or Death in Hepatitis A
      Related Acute Liver Failure.
AB  - Acute liver failure (ALF) caused by hepatitis A is a rare but fatal disease.
      Here, we developed a model to predict outcome in patients with ALF caused by
      hepatitis A. The derivation set consisted of 294 patients diagnosed with
      hepatitis A-related ALF from Korea, and a validation set of 56 patients from
      Japan, India, and United Kingdom. Using multivariate proportional hazard model, a
      risk-prediction model (ALFA score) comprised of age, international normalized
      ratio, bilirubin, ammonia, creatinine, and hemoglobin levels acquired on the day
      of ALF diagnosis was developed. The ALFA score showed the highest discrimination
      in the prediction of liver transplant or death at 1 month (c-statistic, 0.87; 95%
      confidence interval [CI], 0.84-0.92) versus King's College criteria (KCC; c
      statistic, 0.56; 95% CI, 0.53-0.59), US Acute Liver Failure Study Group index
      specific for hepatitis A virus (HAV-ALFSG; c-statistic, 0.70; 95% CI, 0.65-0.76),
      the new ALFSG index (c-statistic, 0.79; 95% CI, 0.74-0.84), Model for End-stage
      Liver Disease (MELD; c-statistic, 0.79; 95% CI, 0.74-0.84) and MELD including
      sodium (MELD-Na; c-statistic, 0.78; 95% CI, 0.73-0.84) in the derivation set (all
      P<0.01). In the validation set, the performance of the ALFA score (c-statistic,
      0.84; 95% CI, 0.74-0.94) was significantly better than that of KCC (c-statistic,
      0.65; 95% CI, 0.52-0.79), MELD (c-statistic, 0.74; 95% CI, 0.61-0.87), and MELD
      Na (c-statistic, 0.72; 95% CI, 0.58-0.85) (all P < 0.05) and better, but not
      statistically significant, than that of the HAV-ALFSG (c-statistic, 0.76; 95% CI,
      0.61-0.90; P=0.28) and new ALFSG indices (c-statistic, 0.79; 95% CI, 0.65-0.93;
      P=0.41). The model was well calibrated in both sets. Conclusion Our new disease
      specific score provides refined prediction of outcome in patients with ALF caused
      by hepatitis A. This article is protected by copyright. All rights reserved.

PMID- 30194741
TI  - Alkanethiol-functionalized organosilicon monoliths for nano-reversed-phase liquid
      chromatography.
AB  - Organosilicon monoliths carrying chromatographic ligands with different alkyl
      chain lengths were obtained by thiol-methacrylate photopolymerization. The use of
      thiol-ene chemistry in the presence of a main monomer with a series of
      methacrylate functionality (i.e., methacrylate substituted polyhedral oligomeric
      silsesquioxane) allowed the synthesis of organosilicon monoliths with high cross
      linking density and carrying hydrophobic alkyl-chain ligands by a one-pot
      process. In the synthesis runs, 1-butanethiol, 1-octanethiol, and 1
      octadecanethiol were used as the hydrophobic thiol ligands with the number of
      methylene units between 4 and 18. The selectivity analysis performed using
      cytosine/uracil retention ratio showed that alkanethiol-attached organosilicon
      monoliths exhibited hydrophobicity close to octadecyl-attached silica-based RP
      columns. In the RP, chromatographic runs performed in nano-liquid chromatography,
      phenols, alkylbenzenes, and PAHs were used as the analytes. Among the synthesized
      monoliths, retention-independent plate height behavior and the smallest plate
      heights were obtained with 1-octadecanethiol-attached organosilicon monolith for
      the analytes in a wide polarity range. With this monolith, the mobile phases
      prepared with ACN contents ranging between 35 and 85% v/v could be used for
      satisfactory separation of analytes in a wide polarity range.

PMID- 30194742
TI  - CEST imaging at 9.4 T using adjusted adiabatic spin-lock pulses for on- and off
      resonant T1?-dominated Z-spectrum acquisition.
AB  - PURPOSE: The CEST experiment, with its correlation to rare proton species that
      are in exchange with the water pool, is very similar to the off-resonant water
      spin-lock (SL) experiment. In particular, low-power SL Z-spectrum acquisition
      allows insight into T1rho and exchange effects with decreased direct water
      saturation. Because the available SL methods either require high B1 power or are
      instable in the presence of strong B1 and B0 inhomogeneity present at ultra-high
      fields, the goal of this study was to find a robust adiabatic SL pulse for on-
      and off-resonant application in the human brain at 9.4 T. METHODS: A series of
      Bloch simulations were used to find optimal pulse shape parameters of an adjusted
      hyperbolic secant pulse applicable in the low power regime typically used for
      exchange-weighted SL experiments. The optimized pulse was implemented and tested
      in phantom and in vivo experiments on a 9.4 T human scanner for on- and off
      resonant T1rho - and Z-spectrum measurements. RESULTS: The simulation yielded a
      feasible pulse shape, which yielded robust images, less sensitivity to B1 and B0
      inhomogeneity compared with previous SL approaches and less direct water
      saturation, as well as a higher chemical exchange weighting compared with
      conventional CEST approaches. CONCLUSION: By adapting a pulse shape for low-power
      SL experiments, we were able to acquire robust on- and off-resonant adiabatic SL
      prepared images in vivo at 9.4 T. This development leads directly to SL Z
      spectrum acquisition, beneficial for chemical-exchange-weighted MRI.

PMID- 30194743
TI  - Acylated catalpol diglycoside ameliorates lipopolysaccharides-induced acute lung
      injury through inhibition of iNOS and TNF-alpha expression.
AB  - Acute lung injury (ALI) is a universal cause of respiratory failure and death
      especially after sepsis. The current study evaluates the protective efficacy of
      acylated catalpol diglycoside (ACD), a plant iridoid glycoside, against
      lipopolysaccharides (LPS)-induced ALI in rats. ACD prevented LPS-induced
      elevations in total and differential cell counts and total protein content in
      bronchoalveolar lavage fluid, lung malondialdehyde content, and serum lactate
      dehydrogenase activity. Moreover, ACD significantly increased lung glutathione
      and superoxide dismutase and improved lung histopathology with significant
      reduction in lung tumor necrosis factor-alpha (TNF-alpha) content mediated mainly
      via inhibition of TNF-alpha messenger RNA (mRNA) expression. In addition, ACD
      significantly reduced lung total nitrate concentration content through
      downregulation of inducible nitric oxide synthase (iNOS) mRNA expression,
      negating the excessive undesired vasodilatation characteristic to sepsis. In
      conclusion, the reduction of oxidative stress, amelioration of inflammatory
      cytokines expression, and antagonism of sepsis associated-excessive
      vasodilatation are main contributors in ACD's protective effect in LPS-induced
      ALI in rats.

PMID- 30194744
TI  - Comparison of the detrimental features of microglia and infiltrated macrophages
      in traumatic brain injury: A study using a hypnotic bromovalerylurea.
AB  - Microglia and blood-borne macrophages in injured or diseased brains are difficult
      to distinguish because they share many common characteristics. However, the
      identification of microglia-specific markers and the use of flow cytometry have
      recently made it easy to discriminate these types of cells. In this study, we
      analyzed the features of blood-borne macrophages, and activated and resting
      microglia in a rat traumatic brain injury (TBI) model. Oxidative injury was
      indicated in macrophages and neurons in TBI lesions by the presence of 8-hydroxy
      2'-deoxyguanosine (8-OHdG). Generation of mitochondrial reactive oxygen species
      (ROS) was markedly observed in granulocytes and macrophages, but not in activated
      or resting microglia. Dihydroethidium staining supported microglia not being the
      major source of ROS in TBI lesions. Furthermore, macrophages expressed NADPH
      oxidase 2, interleukin-1beta (IL-1beta), and CD68 at higher levels than
      microglia. In contrast, microglia expressed transforming growth factor beta1
      (TGFbeta1), interleukin-6 (IL-6), and tumor necrosis factor alpha at higher
      levels than macrophages. A hypnotic, bromovalerylurea (BU), which has anti
      inflammatory effects, reduced both glycolysis and mitochondrial oxygen
      consumption. BU administration inhibited chemokine CCL2 expression, accumulation
      of monocytes/macrophages, 8-OHdG generation, mitochondrial ROS generation, and
      proinflammatory cytokine expression, and markedly ameliorated the outcome of the
      TBI model. Yet, BU did not inhibit microglial activation or expression of
      TGFbeta1 and insulin-like growth factor 1 (IGF-1). These results indicate that
      macrophages are the major aggravating cell type in TBI lesions, in particular
      during the acute phase. Activated microglia may even play favorable roles.
      Reduction of cellular energy metabolism in macrophages and suppression of CCL2
      expression in injured tissue may lead to amelioration of TBI.

PMID- 30194745
TI  - Noninvasive Prediction of IDH1 Mutation and ATRX Expression Loss in Low-Grade
      Gliomas Using Multiparametric MR Radiomic Features.
AB  - BACKGROUND: Noninvasive detection of isocitrate dehydrogenase 1 mutation
      (IDH1(+)) and loss of nuclear alpha thalassemia/mental retardation syndrome X
      linked expression ((ATRX(-)) are clinically meaningful for molecular
      stratification of low-grade gliomas (LGGs). PURPOSE: To study a radiomic approach
      based on multiparametric MR for noninvasively determining molecular status of
      IDH1(+) and ATRX(-) in patients with LGG. STUDY TYPE: Retrospective, radiomics.
      POPULATION: Fifty-seven LGG patients with IDH1(+) (n = 36 with 19 ATRX(-) and 17
      ATRX(+) patients) and IDH1(-) (n = 21). FIELD STRENGTH/SEQUENCE: 3.0T MRI / 3D
      arterial spin labeling (3D-ASL), T2 /fluid-attenuated inversion recovery (T2
      FLAIR), and diffusion-weighted imaging (DWI). ASSESSMENT: In all, 265 high
      throughput radiomic features were extracted on each tumor volume of interest from
      T2 FLAIR and the other three parametric maps of ASL-derived cerebral blood flow
      (CBF), DWI-derived apparent diffusion coefficient (ADC), and exponential ADC
      (eADC). Optimal feature subsets were selected as using the support vector machine
      with a recursive feature elimination algorithm (SVM-RFE). Receiver operating
      characteristic curve (ROC) analysis was employed to assess the efficiency for
      identifying the IDH1(+) and ATRX(-) status. STATISTICAL TESTS: Student's t-test,
      chi-square test, and Fisher's exact test were applied to confirm whether
      intergroup significant differences exist between molecular subtypes decided by
      IDH1 and ATRX. RESULTS: Optimal SVM predictive models of IDH1(+) and ATRX(-) were
      established using 28 features from T2 Flair, ADC, eADC, and CBF and six features
      from T2 Flair, ADC, and CBF. The accuracies/AUCs/sensitivity/specifity/PPV/NPV of
      predicting IDH1(+) in LGG were 94.74%/0.931/100%/85.71%/92.31%/100%, and those of
      predicting ATRX(-) in LGG with IDH1(+) were
      91.67%/0.926/94.74%/88.24%/90.00%/93.75%, respectively. DATA CONCLUSION: Using
      the optimal texture features extracted from multiple MR sequences or parametric
      maps, a promising stratifying strategy was acquired for predicting molecular
      subtypes of IDH1 and ATRX in LGGs. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage:
      2 J. MAGN. RESON. IMAGING 2018.

PMID- 30194746
TI  - Measurements of Diffusion and Perfusion in Vertebral Bone Marrow Using Intravoxel
      Incoherent Motion (IVIM) With Multishot, Readout-Segmented (RESOLVE) Echo-Planar
      Imaging.
AB  - BACKGROUND: A limited number of studies have used the intravoxel incoherent
      motion (IVIM) approach on bone marrow. In none of the previous studies were the
      effects of fat suppression on the IVIM parameters investigated. PURPOSE: To
      measure the water diffusion coefficient and the perfusion fraction in vertebral
      bone marrow using IVIM with multishot, readout-segmented (RESOLVE) echo-planar
      imaging and to assess the effects of different fat suppression techniques on the
      measurement of the IVIM parameters. STUDY TYPE: Prospective. POPULATION/SUBJECTS:
      Six healthy volunteers (24.2 +/- 4.3 years). FIELD STRENGTH/SEQUENCE: 1.5T,
      RESOLVE. ASSESSMENT: Four experiments were performed: 1) RESOLVE imaging without
      fat suppression, 2) with fat saturation (FS), 3) with spectral attenuated
      inversion recovery (SPAIR), and 4) with short-tau inversion recovery (STIR). The
      water diffusion coefficient D, pseudo-diffusion coefficient D*, and the perfusion
      fraction f were assessed in the vertebral bodies of the lumbar vertebrae.
      STATISTICAL TESTS: One-way repeated-measures analysis of variance (ANOVA)
      followed by Bonferroni's multiple comparison test. RESULTS: The RESOLVE IVIM
      protocol allowed for measurement of D, D*, and f in all volunteers. The signal of
      lipid protons affected the quantification of the IVIM diffusion coefficient: D =
      0.24 +/- 0.10 (*10-3 mm2 /s), no FS; D = 0.43 +/- 0.07 (*10-3 mm2 /s), FS; D =
      0.42 +/- 0.07 (*10-3 mm2 /s), SPAIR; D = 0.35 +/- 0.10 (*10-3 mm2 /s), STIR; and
      IVIM perfusion fraction f = 7.5 +/- 1.9% no FS, f = 14.5 +/- 5.4%, FS; f = 12.5
      +/- 2.6%, SPAIR; f = 18.1 +/- 6.1%, STIR. No significant effect (P = 0.36) was
      found on the quantification of D*. DATA CONCLUSION: An IVIM-MRI protocol using
      the RESOLVE sequence was implemented for measurements of vertebral bone marrow
      diffusion and the perfusion. The comparison between the protocols with and
      without fat suppression indicates that the lipid signal results in an
      underestimation of both D and f. LEVEL OF EVIDENCE: Technical Efficacy Stage: 1
      J. MAGN. RESON. IMAGING 2018.

PMID- 30194747
TI  - Long-term change in bioconstruction potential of Maldivian coral reefs following
      extreme climate anomalies.
AB  - Global climate change has increased the frequency and intensity of extreme heat
      anomalies and consequent mass coral bleaching events. Long-term dynamics of hard
      coral cover, bioconstruction potential, carbonate deposition, and reef accretion
      was monitored over a 20-year period on Maldivian coral reefs in order to
      investigate the effects of high-temperature anomalies on coral reef accretion and
      their recovery potential. Changes experienced by shallow reefs between 1997 and
      2017 were evaluated by considering five different bioconstructional guilds and
      the BioConstruction Potential index (BCP), a proxy for the constructional
      capacity of reefs. Abnormally high temperatures in 1998 and 2016 led to severe
      coral bleaching and consequent mortality, especially of the primary builders.
      Renewed carbonate deposition was not documented until 2-3 years after the
      bleaching, and 6-9 years passed until constratal (i.e., low relief) growth was
      achieved. Finally, 14-16 years were required to reach accretion rates high enough
      to ensure superstratal (i.e., high relief) growth. Coral mortality in the
      Maldives during the 2016 bleaching event was lower than in 1998, and the initial
      recovery was faster and occurred via a different trajectory than in 1998. Rising
      levels of anthropogenic carbon emissions are predicted to accelerate sea level
      rise and trigger severe coral bleaching events at least twice per decade, a
      frequency that will (a) prevent coral recovery, (b) nullify reef accretion, and
      consequently, (c) result in the drowning of Maldivian reefs under the worst
      climate projections.

PMID- 30194749
TI  - Abbreviated MRI of the Breast: Does It Provide Value?
AB  - : MRI of the breast is the most sensitive test for breast cancer detection and
      outperforms conventional imaging with mammography, digital breast tomosynthesis,
      or ultrasound. However, the long scan time and relatively high costs limit its
      widespread use. Hence, it is currently only routinely implemented in the
      screening of women at an increased risk of breast cancer. To overcome these
      limitations, abbreviated dynamic contrast-enhanced (DCE)-MRI protocols have been
      introduced that substantially shorten image acquisition and interpretation time
      while maintaining a high diagnostic accuracy. Efforts to develop abbreviated MRI
      protocols reflect the increasing scrutiny of the disproportionate contribution of
      radiology to the rising overall healthcare expenditures. Healthcare policy makers
      are now focusing on curbing the use of advanced imaging examinations such as MRI
      while continuing to promote the quality and appropriateness of imaging. An
      important cornerstone of value-based healthcare defines value as the patient's
      outcome over costs. Therefore, the concept of a fast, abbreviated MRI exam is
      very appealing, given its high diagnostic accuracy coupled with the possibility
      of a marked reduction in the cost of an MRI examination. Given recent concerns
      about gadolinium-based contrast agents, unenhanced MRI techniques such as
      diffusion-weighted imaging (DWI) are also being investigated for breast cancer
      diagnosis. Although further larger prospective studies, standardized imaging
      protocol, and reproducibility studies are necessary, initial results with
      abbreviated MRI protocols suggest that it seems feasible to offer screening
      breast DCE-MRI to a broader population. This article aims to give an overview of
      abbreviated and fast breast MRI protocols, their utility for breast cancer
      detection, and their emerging role in the new value-based healthcare paradigm
      that has replaced the fee-for-service model. LEVEL OF EVIDENCE: 1 Technical
      Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2018.

PMID- 30194750
TI  - neogen: A tool to predict genetic effective population size (Ne ) for species
      with generational overlap and to assist empirical Ne study design.
AB  - Molecular genetic estimates of population effective size (Ne ) lose accuracy and
      precision when insufficient numbers of samples or loci are used. Ideally,
      researchers would like to forecast the necessary power when planning their
      project. neogen (genetic Ne for Overlapping Generations) enables estimates of
      precision and accuracy in advance of empirical investigation and allows
      exploration of the power available in different user-specified age-structured
      sampling schemes. neogen provides a population simulation and genetic power
      analysis framework that simulates the demographics, genetic composition, and Ne ,
      from species-specific life history, mortality, population size, and genetic
      priors. neogen guides the user to establish a tractable sampling regime and to
      determine the numbers of samples and microsatellite or SNP loci required for
      accurate and precise genetic Ne estimates when sampling a natural population.
      neogen is useful at multiple stages of a study's life cycle: when budgeting, as
      sampling and locus development progresses, and for corroboration when empirical
      Ne estimates are available. The underlying model is applicable to a wide variety
      of iteroparous species with overlapping generations (e.g., mammals, birds,
      reptiles, long-lived fishes). In this paper, we describe the neogen model, detail
      the workflow for the point-and-click software, and explain the graphical results.
      We demonstrate the use of neogen with empirical Australian east coast zebra shark
      (Stegostoma fasciatum) data. For researchers wishing to make accurate and precise
      genetic Ne estimates for overlapping generations species, neogen facilitates
      planning for sample and locus acquisition, and with existing empirical genetic Ne
      estimates neogen can corroborate population demographic and life history
      properties.

PMID- 30194751
TI  - Dilute Russell viper venom time interpretation and clinical correlation: A two
      year retrospective institutional review.
AB  - INTRODUCTION: The dilute Russell viper venom time (dRVVT) detects lupus
      anticoagulant (LA). International Society for Thrombosis and Haemostasis (ISTH)
      guidelines specify positivity criteria, which differ from the assay
      manufacturer's criteria. METHODS: Two years of dRVVT testing at our institution
      were reviewed. For patients with prolonged dRVVT screening times, we evaluated
      dRVVT results by ISTH and manufacturer's criteria and correlated with the results
      of other antiphospholipid syndrome (APS) testing (LA-sensitive activated partial
      thromboplastin time and antiphospholipid antibodies) and with history of
      thromboembolism and other APS manifestations. RESULTS: Approximately one-fifth of
      dRVVTs exhibited a prolonged screening time. Among first prolonged dRVVTs, 35%
      were positive by both ISTH and manufacturer criteria, 44% met neither criteria,
      and 20% were equivocal (positive by only ISTH or manufacturer). Positivity by
      ISTH guidelines alone correlated better with other positive APS tests than
      manufacturer criteria positivity. Positive dRVVTs by both criteria correlated
      even more strongly with other positive APS assays. We investigated the likelihood
      of eventual APS diagnosis depending on the testing indication. No patient tested
      for LA solely for prolonged screening aPTT was subsequently diagnosed with APS.
      In patients with thrombosis, prolonged dRVVT clotting time not meeting both ISTH
      and manufacturer criteria was rarely associated with eventual APS diagnosis.
      CONCLUSION: We examined the correlation of dRVVT results with other APS testing
      and clinical outcomes. Interpretation method impacted how dRVVT results related
      to other APS testing, and, in limited data, to clinical findings. Patients with
      prolonged dRVVTs meeting only one set of positivity criteria rarely received an
      APS diagnosis.

PMID- 30194752
TI  - Collaborative Remembering in Conversational Narration.
AB  - This chapter introduces an epistemic perspective on narration and illustrates,
      based on data from storytelling in free natural conversation, how collaborative
      remembering can instantiate distributed cognition: first, when tellers deploy
      expressions of forgetfulness or explicitly enlist the aid of other participants;
      second, during various forms of collaborative turn sequencing with rapid speaker
      shift and a high degree of overlap; third, when conversational participants
      cooperate to produce a mosaic-like narrative consisting of their partially
      separate perspectives and contributions; and fourth, when they weave their voices
      into a single narrative thread in a Goffmanian team performance.

PMID- 30194753
TI  - Noma surgery.
AB  - OBJECTIVE: Noma is a devastating and destructive disease of the face for which
      there is a dearth of information regarding surgical options. Herein, we describe
      the facial deformities and patient characteristics in a patient population
      affected by noma and the surgical approaches used in treatment. METHODS:
      Retrospective case series of a Doctors Without Borders (Medecins Sans Frontieres)
      intervention at Sokoto Children's Noma Hospital in northern Nigeria, the highest
      volume noma hospital in the world. RESULTS: Twenty-two procedures were performed
      on 18 patients with noma, 44% of whom were children. The majority of patients (n
      = 10, 55.5%) were made aware of surgical care through a Doctors Without Borders
      outreach program. Patients' reasons for seeking care included functional (61.1%,
      n = 11), appearance (61.1%, n = 11), and social stigma (66.7%, n = 12). The
      majority (83.3%, n = 15) had lip involvement. Four patients (22.2%) underwent
      staged flap procedures including prelamination, flap delay, or pedicle division.
      The mean duration of surgical procedure was 87 minutes (range 5-306 minutes). The
      minor complication rate was 16%. There were no major complications or deaths.
      CONCLUSION: Noma is a mutilating disease of the face that occurs in settings of
      extreme malnutrition. A total of 55.5% of noma patients were made aware of
      surgical care through outreach programs. The majority of noma patients seek care
      to improve function (61.1%) and appearance (61.1%), and to address social stigma
      (66.7%). A total of 83.3% of noma patients had lip involvement. Facial
      reconstructive surgeons must rely on principles of congenital, traumatic, and
      oncologic deformity repair while focusing on safe, reliable procedures for low
      resource settings. LEVEL OF EVIDENCE: 4. Laryngoscope, 2018.

PMID- 30194754
TI  - Selection for pollen competitive ability in mixed-mating systems.
AB  - Coexpression of genes in plant sporophytes and gametophytes allows correlated
      gametic and sporophytic selection. Theory predicts that, under outcrossing, an
      allele conferring greater pollen competitive ability should fix within a
      population unless antagonistic pleiotropy with the sporophyte stage is strong.
      However, under strong selfing, pollen competitiveness is immaterial as superior
      and inferior competitors are deposited on opposite stigmas, producing assortative
      competition. Because many plant species have mixed-mating systems, selfing should
      be critical in the spread and maintenance of pollen-expressed genes affecting
      competitiveness. We present two one-locus, two-allele population genetic models
      for the evolution of a locus controlling pleiotropic antagonism between pollen
      competitiveness and diploid fitness. Analytical solutions provide minimum and
      maximum selfing rates allowing invasion of alleles with greater diploid and
      haploid fitness, respectively. Further, polymorphism is only maintained when
      diploid selection is recessive. Fixation of the allele conferring greater pollen
      competitiveness may be prevented, even with weak sporophytic counterselection,
      with sufficiently high selfing. Finally, selfing expands and limits the range of
      haploid-diploid selection coefficients allowing polymorphism, depending on
      dominance and selfing mode.

PMID- 30194755
TI  - Antiepileptic monotherapy in newly diagnosed focal epilepsy. A network meta
      analysis.
AB  - Second and third generation AEDs have been directly compared to controlled
      release carbamazepine (CBZ-CR) as initial monotherapy for new-onset focal
      epilepsy. Conversely, no head-to-head trials have been performed. The aim of this
      study was to estimate the comparative efficacy and tolerability of the
      antiepileptic monotherapies in adults with newly diagnosed focal epilepsy through
      a network meta-analysis (NMA). Randomized, double-blinded, parallel group,
      monotherapy studies comparing any AED to CBZ-CR in adults with newly diagnosed
      untreated epilepsy with focal-onset seizures was identified. The outcome measures
      were the seizure freedom for 6 and 12 months, the occurrence of treatment
      emergent adverse events (TEAEs), and the treatment withdrawal due to TEAEs. Mixed
      treatment comparisons were conducted by a Bayesian NMA using the Markov chain
      Monte Carlo methods. Effect sizes were calculated as odds ratios (ORs) with 95%
      credible intervals (CrIs). Four trials were included involving 2856 participants,
      1445 for CBZ-CR and 1411 for the comparative AEDs. Monotherapy AEDs compared to
      CBR-CR were levetiracetam (LEV), zonisamide (ZNS), lacosamide (LCM), and
      eslicarbazepine acetate (ESL). There were no statistical differences in the 6-
      and 12-month seizure freedom and TEAEs occurrence between LEV, ZNS, LCM, ESL, and
      CBZ-CR In the analysis of drug withdrawal due to TEAEs, LCM treatment was
      associated with a significantly lower discontinuation rate than CBZ-CR (OR 0.659,
      95% CrI 0.428-0.950). LEV, ZNS, LCM, and ESL are effective initial monotherapy
      treatments in adult patients with newly diagnosed focal epilepsy and represent
      suitable alternatives to CBZ-CR.

PMID- 30194756
TI  - Wound healing after transoral angiolytic laser surgery for early glottic
      carcinoma.
AB  - OBJECTIVES/HYPOTHESIS: Wound healing after transoral angiolytic laser surgery for
      early glottic carcinoma was analyzed to identify factors influencing healing and
      clinical significance of persistent granulation tissue. STUDY DESIGN:
      Retrospective review. METHODS: A retrospective review of 100 consecutive patients
      undergoing endoscopic angiolytic laser surgery for T1 and T2 glottic carcinoma
      was performed. Patients with prior radiation or incomplete data were excluded.
      Postoperative endoscopic images were analyzed for time to healing, size and
      location of wound, and presence of granulation tissue. Three blinded, independent
      raters graded wound appearance and presence of granulation tissue. RESULTS:
      Seventy-nine patients healed without need for intervention at a median of 3.5
      months. Two patients had office-based ablation of granulation without biopsy and
      healed. The remaining 19 patients had biopsy for granulation tissue. Wounds that
      underwent biopsy at >3 months were more likely to contain carcinoma (5/6
      patients, 83%) than wounds that were biopsied <3 months (2/13 patients, 15%) (P =
      .004). Presence of granulation significantly correlated with resection involving
      anterior commissure (P = .01), > 75%vocal fold length (P = .006), and depth into
      muscle (P = .001). Delayed healing (>3 months) correlated with T2b tumors (P =
      .02), depth into ligament (P = .002) and anterior commissure involvement (P =
      .04). T1a carcinomas more commonly healed in <3 months (P = .005). CONCLUSIONS:
      Many vocal fold wounds heal completely within 3.5 months after angiolytic laser
      surgery for early glottic carcinoma. Larger and deeper wounds are more likely to
      heal with granulation tissue. Granulation can resolve without surgical
      intervention; however, granulation present > 3 months warrants biopsy due to
      increased risk of malignancy. LEVEL OF EVIDENCE: 4 Laryngoscope, 2018.

PMID- 30194757
TI  - A two-locus hybrid incompatibility is widespread, polymorphic, and active in
      natural populations of Mimulus.
AB  - Reproductive isolation, which is essential for the maintenance of species in
      sympatry, is often incomplete between closely related species. In these taxa,
      reproductive barriers must evolve within species, without being degraded by
      ongoing gene flow. To better understand this dynamic, we investigated the
      frequency and geographic distribution of alleles underlying a two-locus, hybrid
      lethality system between naturally hybridizing species of monkeyflower (Mimulus
      guttatus and M. nasutus). We found that M. guttatus typically carries hybrid
      lethality alleles at one locus (hl13) and M. nasutus typically carries hybrid
      lethality alleles at the other locus (hl14). As a result, natural hybrids carry
      incompatible alleles at both loci, and express hybrid lethality in later
      generations. We also discovered considerable polymorphism at both hl13 and hl14
      within both species. For M. guttatus, polymorphism at both loci occurs within
      populations, meaning that incompatible allele pairings likely arise through
      intraspecific gene flow. Genetic variation at markers linked to hl13 and hl14
      suggest that introgression from M. nasutus is the primary driver of this
      polymorphism within M. guttatus. Additionally, patterns of introgression at the
      two hybrid lethality loci suggest that natural selection eliminates incompatible
      allele pairings, suggesting that even weak reproductive barriers might promote
      genomic divergence between species.

PMID- 30194758
TI  - Image gallery: Hairy-cell leukaemia presenting with Sweet syndrome.
AB  - A 57-year-old man presented with a 1-month history of fevers, dermatitis and
      pancytopenia in the setting of a 14-lb weight loss, fatigue, night sweats and
      arthralgia. Skin examination revealed multiple erythematous papules on the (a)
      trunk and (b) extremities. Erythrocyte sedimentation rate and C-reactive protein
      were elevated (104 mm h-1 and 14.8 mg L-1 , respectively). This article is
      protected by copyright. All rights reserved.

PMID- 30194759
TI  - Placenta-conditioned extracellular matrix (ECM) activates breast cancer cell
      survival mechanisms: A key for future distant metastases.
AB  - The extracellular matrix (ECM) affects cancer cell characteristics. Inability of
      normal epithelial cells to attach to the ECM induces apoptosis (anoikis). Cancer
      cells are often anoikis resistant, a prerequisite for their metastatic spread.
      Previously we demonstrated that the placenta manipulates its surrounding ECM in a
      way that prevents breast cancer cells (BCCL) attachment and induces their
      motility and aggregation. This fits with the fact that although breast cancer
      during pregnancy is often advanced, metastasis to the placenta is rarely
      observed. Placental intervillous space provides suitable conditions for cancer
      cell arrival. Yet, the outcome of the short communication between the placental
      ECM to the BCCL and its effect on BCCL malignant potential are unknown, and are
      the focus of this study. In the current study we analyzed the effect of placental
      ECM on BCCL survival pathways and drug resistance. Microarray analysis suggested
      activation of the NF-kappaB and stress response pathways. Indeed, the placenta
      conditioned ECM induced autophagy in ERalpha+ BCCL, inactivated the NF-kappaB
      inhibitor (IkappaB) and increased integrin alpha5 in the BCCL. The autophagy
      mediated MCF-7 and T47D migration and the placental ECM-BCCL interactions reduced
      the BCCL sensitivity to Taxol. We also demonstrated by using siRNA that integrin
      alpha5 was responsible for the MCF-7 autophagy and suggest this molecule as a
      suitable target for therapy. This article is protected by copyright. All rights
      reserved.

PMID- 30194760
TI  - The incidence of microscopic thyroglossal duct tissue superior to the hyoid bone.
AB  - OBJECTIVE: Despite the success of the Sistrunk procedure, persistence of a
      thyroglossal duct cyst (TGDC), sinus, or remnant following excision remains a
      clinical problem. This is most likely due to the presence of microscopic disease
      that was not excised at the time of surgery. The purpose of this study is to
      determine the incidence of microscopic disease superior to the hyoid bone in
      children who have had either a primary or revision procedure for a TGDC. METHODS:
      A prospective review of pathologic specimens was conducted of all consecutive
      patients undergoing TGDC excision by pediatric otolaryngologists at the
      Children's Hospital Los Angeles beginning March 2014 through July 2017 in both
      primary and revision procedures. RESULTS: Microscopic disease was present
      superior to the hyoid bone in 25 of the 34 (74%) specimens and in 100% (6) of the
      specimens from a revision procedure. CONCLUSION: The majority of persons who have
      a TGDC will have microscopic disease superior to the hyoid bone. In order to
      minimize the incidence of persistence following a primary procedure, tissue
      superior to the hyoid bone should be removed routinely even if no gross disease
      is noted at the time of surgery. When performing a revision procedure, special
      attention should be given to the suprahyoid area as a likely site of persistent
      disease. LEVEL OF EVIDENCE: 2b. Laryngoscope, 2018.

PMID- 30194761
TI  - Body composition and body mass index in Duchenne dystrophy: Role of dietary
      intake.
AB  - INTRODUCTION: In Duchenne muscular dystrophy (DMD) muscle is replaced by adipose
      tissue. The role of dietary intake (DI) in DMD has not been evaluated. We
      examined body composition , BMI and adequacy of DI in patients with DMD and
      evaluated the influence of DI on body composition. METHODS: Patients (n=101; age
      3 to 18 years; BMI 11.8 to 29.5 kg/m2 ) completed a dietary recall to determine
      DI and underwent dual-energy x-ray absorptiometry to determine body composition.
      RESULTS: Preschool-age and school-age boys with DMD had high total energy intake.
      Protein intake/kg exceeded recommendations. As age increased, the percentage of
      boys with abnormal BMI and fat mass increased, while lean mass decreased. Dietary
      intake did not predict body fat or lean mass. DISCUSSION: Age dependent changes
      in BD in boys with DMD may be due to endogenous metabolic factors related to the
      underlying disease process and to disease-related mobility impairments. This
      article is protected by copyright. All rights reserved.

PMID- 30194762
TI  - Positive surgical margins in parotid malignancies: Institutional variation and
      survival association.
AB  - OBJECTIVES/HYPOTHESIS: To establish benchmarks for positive margin incidence in
      parotid cancers, associate positive margin status with patient, tumor, and
      institutional factors and overall survival, and characterize institutional
      variation in positive margin incidence. STUDY DESIGN: Retrospective database
      analysis. METHODS: We identified patients surgically treated for a parotid
      malignancy 2004 to 2013 in the National Cancer Database. We associated positive
      margins with patient, tumor, and treatment factors by multivariable logistic
      regression and with overall survival by Cox proportional hazards regression. We
      characterized institutional variation in positive margin rates by facility type
      and volume. RESULTS: A total of 5,639 patients were identified. The overall
      positive margin rate was 31%. By institution, positive margin rates varied from
      0% to 100%, with a median rate of 31% (interquartile range = 18%-43%). Adenoid
      cystic carcinoma was associated with increased, and low-grade mucoepidermoid
      carcinoma with decreased, odds of positive margins, (odds ratio [OR] = 1.91 [95%
      confidence interval {CI}: 1.54-2.38], P < .001 and OR = 0.68 [95% CI: 0.53-0.87],
      P = .002, respectively). Treatment at academic or high-volume facilities was
      associated with decreased odds of positive margins (OR = 0.79 [95% CI: 0.68
      0.91], P = .001 and OR = 0.76 [95% CI: 0.63-0.91], P = .004). Positive surgical
      margins were associated with decreased overall survival (62% vs. 79% 5-year
      overall survival, hazard ratio [HR] = 1.34 [95% CI: 1.20-1.49], P < .001). Upon
      stratification by histology, this association was maintained for high-grade, but
      not low-grade, mucoepidermoid carcinoma (52% vs. 74%, HR = 1.56 [95% CI: 1.31
      1.86], P < .001 and 89% versus 91%, HR = 1.05 [95% CI: 0.60-1.83], P = .874,
      respectively). CONCLUSIONS: Tumor and institutional factors are associated with
      positive surgical margins. Positive margin rates vary substantially between
      facilities and are less likely at academic and high-volume facilities. Positive
      surgical margins are associated with decreased overall survival and could be
      considered quality indicators in parotid malignancies. LEVEL OF EVIDENCE: 2c
      Laryngoscope, 2018.

PMID- 30194763
TI  - Current practices in microvascular reconstruction in otolaryngology-head and neck
      surgery.
AB  - OBJECTIVES/HYPOTHESIS: Despite major advances in the field of head and neck
      microvascular free tissue transfer (MFTT) over the past several decades, there
      are no standardized perioperative regimens for the care of patients undergoing
      free flap reconstructive surgery, and continued variation in practice exists.
      This study aimed to report current trends in the field of MFTT performed by
      otolaryngologists, including surgeon training, institutional operative practices,
      and perioperative management. STUDY DESIGN: Cross-sectional survey. METHODS: A
      survey of Accreditation Council for Graduate Medical Education-accredited
      residency programs and American Head and Neck Society fellowship sites was
      conducted. RESULTS: Seventy-one (62.8%) programs responded, with 67 (94.4%)
      routinely performing MFTT and 23 (32.4%) having a dedicated microvascular
      fellowship program. Of institutions performing MFTT, 66 (98.5%) reported the use
      of a two-surgeon team, most commonly both otolaryngologists (76.3%).
      Institutional MFTT volumes and donor site frequency are reported. Postoperative
      care includes routine admission to the intensive care unit (75.2%), step-down
      unit (15.0%), or general care floor (8.1%). Postoperative flap monitoring
      practices, including modalities, personnel, and timing/frequency show
      institutional variation. Despite differences in postoperative monitoring regimen
      and management (sedation, anticoagulation, antibiotic use), surgeon-reported
      measures of flap success rate (95.7%, standard deviation [SD] 4.7%) and
      complication rate (6.8%, SD 2.4%) show little difference across institutions.
      CONCLUSIONS: Many elements of MFTT perioperative care show continued variation at
      an institutional level. There is a notable shift toward the two-team approach
      within otolaryngology. Self-reported flap complication and success rates showed
      no significant differences based on perioperative care and monitoring regimen.
      Further study of perioperative practices should focus on standardization of care
      to improve overall outcomes in this complex patient population. LEVEL OF
      EVIDENCE: NA Laryngoscope, 2018.

PMID- 30194764
TI  - PDEdelta inhibition impedes the proliferation and survival of human colorectal
      cancer cell lines harboring oncogenic KRas.
AB  - Ras proteins, most notably KRas, are prevalent oncogenes in human cancer. Plasma
      membrane localization and thereby signaling of KRas is regulated by the prenyl
      binding protein PDEdelta. Recently, we have reported the specific anti
      proliferative effects of PDEdelta inhibition in KRas-dependent human pancreatic
      ductal adenocarcinoma cell lines. Here, we investigated the proliferative
      dependence on the solubilizing activity of PDEdelta of human colorectal cancer
      (CRC) cell lines with or without oncogenic KRas mutations. Our results show that
      genetic and pharmacologic interference with PDEdelta specifically inhibits
      proliferation and survival of CRC cell lines harboring oncogenic KRas mutations
      whereas isogenic cell lines in which the KRas oncogene has been removed, or cell
      lines with oncogenic BRaf mutations or EGFR overexpression are not dependent on
      PDEdelta. Pharmacological PDEdelta inhibition is therefore a possible new avenue
      to target oncogenic KRas bearing CRC.

PMID- 30194765
TI  - Cardiovascular endpoints for obstructive sleep apnea with twelfth cranial nerve
      stimulation (CARDIOSA-12): Rationale and methods.
AB  - OBJECTIVES/HYPOTHESIS: To determine the effect of therapeutic levels of
      hypoglossal nerve stimulation therapy (HGNS), compared to subtherapeutic levels
      of HGNS, on 24-hour ambulatory blood pressure, sympathetic activity, and vascular
      function. STUDY DESIGN: Double-blind, sham-controlled, randomized crossover trial
      of 10-week duration at a university medical center METHODS: The target enrollment
      is 60 randomly assigned subjects. Interventions are active versus sham
      (subtherapeutic) HGNS therapy. RESULTS: The primary outcome is 24-hour ambulatory
      systolic blood pressure. Secondary outcomes include 24-hour ambulatory diastolic
      blood pressure, nocturnal systolic and diastolic pressure, muscle sympathetic
      nerve activity, pre-ejection period, flow-mediated dilation, and pulse wave
      velocity. CONCLUSIONS: The Cardiovascular Endpoints for Obstructive Sleep Apnea
      With Twelfth Cranial Nerve Stimulation study is designed to examine obstructive
      sleep apnea and test the effects of HGNS on the cardiovascular system through a
      sham-controlled trial in patients with moderate-severe obstructive sleep apnea.
      LEVEL OF EVIDENCE: 1 Laryngoscope, 2635-2643, 2018.

PMID- 30194766
TI  - Foliar water uptake: Processes, pathways, and integration into plant water
      budgets.
AB  - Nearly all plant families, represented across most major biomes, absorb water
      directly through their leaves. This phenomenon is commonly referred to as foliar
      water uptake. Recent studies have suggested that foliar water uptake provides a
      significant water subsidy that can influence both plant water and carbon balance
      across multiple spatial and temporal scales. Despite this, our mechanistic
      understanding of when, where, how, and to what end water is absorbed through leaf
      surfaces remains limited. We first review the evidence for the biophysical
      conditions necessary for foliar water uptake to occur, focusing on the plant and
      atmospheric water potentials necessary to create a gradient for water flow. We
      then consider the different pathways for uptake, as well as the potential fates
      of the water once inside the leaf. Given that one fate of water from foliar
      uptake is to increase leaf water potentials and contribute to the demands of
      transpiration, we also provide a quantitative synthesis of observed rates of
      change in leaf water potential and total fluxes of water into the leaf. Finally,
      we identify critical research themes that should be addressed to effectively
      incorporate foliar water uptake into traditional frameworks of plant water
      movement.

PMID- 30194767
TI  - Predictors of gastrostomy tube dependence in surgically managed oropharyngeal
      squamous cell carcinoma.
AB  - OBJECTIVES: To elucidate predictive factors in the perioperative period resulting
      in gastrostomy tube (G-tube) dependence for patients undergoing primary surgical
      treatment of oropharyngeal squamous cell carcinoma (OPSCC) in the modern era.
      METHODS: Two hundred and thirty patients with known OPSCC treated with primary
      surgery were screened and selected from a retrospective database spanning from
      2002 to 2012 at The Ohio State University Wexner Medical Center (Columbus, Ohio),
      with univariable and multivariable logistic regression modeling used to determine
      independent predictive factors resulting in G-tube dependence (defined as tube
      persistence/presence 1 year after surgery). RESULTS: Surgical approach, baseline
      characteristics, tumor (T)-nodal-metastasis stage, human papillomavirus status,
      extent of tissue resected, surgical complications, reconstructive technique,
      preoperative G-tube presence, and adjuvant treatment were recorded. Patients
      undergoing open surgery for OPSCC without adjuvant treatment had 42.9% G-tube
      dependence (44.6% with adjuvant chemoradiation [CRT]) compared to 0% for those
      undergoing transoral nonrobotic surgery (8.1% with adjuvant CRT) and 0% for those
      undergoing transoral robotic surgery (10.3% with adjuvant CRT). In multivariable
      analysis, greater than 25% of the oral tongue resected (odds ratio [OR] 12.29; P
      = 0.03), an open surgical approach (OR 5.72; P < 0.01) and T3/T4 tumor stage (OR
      2.84; P = 0.02) were independent and significant predictors of G-tube dependence.
      CONCLUSION: Surgical approach, advanced tumor stage, and oral tongue resection
      may influence the development of nutritional dependence for surgically treated
      patients with OPSCC. LEVEL OF EVIDENCE: 4. Laryngoscope, 2018.

PMID- 30194769
TI  - Unraveling chemotherapy-induced peripheral neuropathy: In vitro and in vivo
      models of sensory nerve dysfunction.

PMID- 30194768
TI  - Disparities in Postoperative Therapy for Salivary Gland Adenoid Cystic
      Carcinomas.
AB  - OBJECTIVES: The patterns of care for salivary gland adenoid cystic carcinomas
      (ACC) are unknown. We sought to assess predictors of receiving postoperative
      radiation and/or chemotherapy for patients with nonmetastatic, definitively
      resected ACC, as well as report unexpected nodal disease. METHODS: The National
      Cancer Data Base was queried for definitively resected nonmetastatic ACC from
      2004 to 2014. Logistic regression, Kaplan-Meier, and Cox proportional-hazard
      models were utilized. Propensity-score matched analysis was employed to reduce
      confounding variables. RESULTS: A total of 3,136 patients met entry criteria:
      2,252 (71.8%) received postoperative radiation, with 223 (7.4%) also receiving
      concurrent chemotherapy. Median follow-up was 4.87 years. In clinically lymph
      node negative (cN0) patients, 7.4% had pathologically positive lymph nodes (pN) +
      after elective neck dissection. Patients who lived closer to their treatment
      facility and had positive margins were more likely to receive postoperative
      radiation. Black patients and uninsured patients were less likely to receive
      radiation. Older age, male sex, advancing stage, and positive surgical margins
      were associated with worse overall survival (OS). With limited follow-up, receipt
      of radiation or chemotherapy was not associated with OS. CONCLUSION:
      Postoperative radiation was frequently given for resected ACC, with a minority
      receiving chemotherapy. Black patients and uninsured patients were less likely to
      receive radiation. Postoperative radiation and/or chemotherapy had no association
      with OS but were given in greater frequency in more advanced disease, and our
      series is limited by short follow-up. The disparity findings for this rare
      disease need to be addressed in future studies. LEVEL OF EVIDENCE: 2c.
      Laryngoscope, 2018.

PMID- 30194770
TI  - Utility and prognostic value of 18 F-FDG positron emission tomography-computed
      tomography scans in patients with newly diagnosed multiple myeloma.
AB  - Positron emission tomography-computed tomography (PET-CT) can identify bony
      lesions, assess disease burden, and detect extramedullary disease (EMD) in
      patients with multiple myeloma. We retrospectively reviewed records of patients
      who underwent PET-CT within 60 days of a new diagnosis (before therapy commenced)
      to identify the nature and prognostic impact of PET-CT abnormalities. Patients (N
      = 313) were seen from April 2005 through June 2017. Of the 234 patients (75%)
      with focal lesions (FLs), 182 (58%) had at least 3 FLs, 38 (12%) had EMD, and 204
      (65%) had documented myelomatous lytic lesions. The median maximum standardized
      uptake value (SUVmax ) for the entire cohort was 5.9 (range 1.5-48.3). Presence
      of at least 3 FLs and EMD predicted inferior overall survival (OS); median OS was
      57.8 months for patients with 3 or more FLs and 103.6 months for patients with
      fewer than 3 FLs (P = .003). The median OS was 45.5 and 71.8 months for patients
      with and without EMD, respectively (P = .004). No clear SUVmax cutoff was
      predictive of progression-free survival or OS. PET-CT is a valuable tool for
      assessing disease burden and could provide prognostic information about a
      contemporary cohort of patients with newly diagnosed myeloma who received
      treatment with novel agents.

PMID- 30194771
TI  - Applications of sensory and physiological measurement in oral-facial dental pain.
AB  - Dentists regularly employ a variety of self-report and sensory techniques to aid
      in the diagnosis and treatment of tooth-related disease. Many of these techniques
      leverage principles borrowed from psychophysics, the quantitative measurement of
      the relationship between stimuli and evoked sensations, which falls under the
      larger umbrella of quantitative sensory testing (QST). However, most clinicians
      fail to meet the bar for what could be considered quantitative sensory testing,
      and instead focus on qualitative and dichotomous "yes/no" aspects of sensory
      experience. With our current subjective measurements for pain assessments,
      diagnosis and treatment of dental pain in young children and individuals (any
      age) with severe cognitive impairment rely extensively on third-party
      observations. Consequently, the limitation of inadequate pain diagnosis can lead
      to poor pain management. In this review, it discusses mechanisms that underlie
      acute and chronic dental pain. It details the measurement of somatosensory
      responses and pulpal blood flow as objective measures of tooth health and pain.
      It proposes that bridging these varied methodologies will significantly improve
      diagnosis and treatment of orofacial pain and pathology. It concludes that
      improving the precision of sensory measurements could yield important
      improvements in diagnostic challenges in pulpal pathology for noncommunicative
      and cognitively impaired individuals.

PMID- 30194772
TI  - miR-21-5p, miR-141-3p, and miR-205-5p levels in urine-promising biomarkers for
      the identification of prostate and bladder cancer.
AB  - BACKGROUND: Early detection of cancers improves patients' survival and decreases
      the treatment cost. Unfortunately, the current methods for diagnosis of bladder
      and prostate cancers, two most common urothelial malignancies, suffer from a low
      sensitivity and specificity. MicroRNAs, as a group of endogenously produced non
      coding RNAs, regulate gene expression and their expression is observed to be
      altered in many cancers and cancer progression phenomena. The remarkable
      stability of microRNAs in biofluids and their unique expression pattern in
      different pathological conditions make them an appealing, noninvasive diagnostic
      method in cancer diagnosis. Our objective is to identify microRNAs as biomarkers
      in urine samples of bladder and prostate cancers to improve the existing
      diagnostic methods in this field. MATERIALS AND METHODS: In this study, urine
      samples from 110 men with either bladder (n = 45) or prostate (n = 23) cancer,
      benign prostatic hyperplasia (n = 22) and healthy controls (n = 20) were
      collected. qPCR was used to evaluate the expression level of miR-21-5p, miR-141
      3p, and miR-205-5p in these samples. The sensitivity and specificity of these
      microRNAs were determined using ROC curve analysis. RESULTS: The analysis of the
      data revealed that miR-21-5p, miR-141-3p, and miR-205-5p are differentially
      expressed in urine of bladder and prostate cancer patients. All these three
      microRNAs were upregulated in these samples and they were also able to
      differentiate benign prostatic hyperplasia from malignant cases. The statistical
      analyses revealed a good specificity for each individual microRNA. CONCLUSION:
      The results show that these three urine-based microRNAs might be a good choice to
      implement a specific and non-invasive diagnostic tool for bladder and prostate
      cancer. The expression pattern of all three microRNAs was particularly useful to
      distinguish benign and invasive tumors in prostate cases. From the patients'
      perspective the improvement of the diagnostic situation is awaited eagerly.

PMID- 30194773
TI  - STAT6 and IL-10 are required for the anti-arthritic effects of Schistosoma
      mansoni via different mechanisms.
AB  - To investigate possible roles of T helper type 2 (Th2) cytokines in the anti
      arthritic effects of a blood fluke, Schistosoma mansoni (Sm), for mouse collagen
      induced arthritis (CIA), wild-type (WT), signal transducer and activator of
      transcription 6 (STAT6) knock-out (KO) and interleukin (IL)-10 KO mice were
      infected with Sm. Three weeks after infection, the mice were immunized with
      bovine type II collagen (IIC). Arthritis severity was monitored by scoring,
      measurement of paw thickness and the presence of ankylosis. Serum anti-IIC IgG
      levels, splenic cytokine production and cytokine gene expression in the popliteal
      lymph nodes (PLNs) were measured and compared among WT and gene-KO mice.
      Consistent with our previous findings, Sm infection reduced the arthritis
      severity in WT mice. Splenic production of IL-17A and tumor necrosis factor (TNF)
      alpha was reduced by the infection. In contrast, Sm infection markedly
      exacerbated CIA in STAT6 KO mice. In the KO mice, IL-17A production was increased
      by the infection. Conversely, Sm infection did not affect the exacerbated
      arthritis in IL-10 KO mice, although IL-17A production was reduced by the
      helminth. Our results suggest that signaling via STAT6 (presumably IL-4 and/or IL
      13) and IL-10 is required for the suppression of CIA by Sm infection, but through
      different mechanisms. STAT6 was essential for helminth-induced reduction of IL
      17A, whereas regulation of the basal arthritis severity by IL-10 was needed in
      order for it to be sufficiently suppressed by the helminth.

PMID- 30194774
TI  - Demographic predictors of head and neck cancer survival differ in the elderly.
AB  - OBJECTIVES/HYPOTHESIS: Head and neck squamous cell carcinoma (HNSCC) prognosis
      strongly correlates with demographic factors. This study aimed to determine
      whether demographic predictors of HNSCC survival differ between age cohorts, with
      an emphasis on the growing elderly demographic. STUDY DESIGN: Outcomes research.
      METHODS: Adults with squamous cell carcinoma of the upper aerodigestive tract
      were identified from the Surveillance, Epidemiology and End Results 18 database.
      Demographic and oncologic factors were compared between three age groups: 18 to
      49, 50 to 74, and >75 years. Factors associated with cancer-specific survival
      were assessed in each cohort using subdistribution hazard ratio (sHR) and 95%
      confidence interval (CI) produced by multivariate competing risk models. RESULTS:
      A cohort of 69,098 patients included 10,588 (15.3%) 75 years or older and 9,882
      (14.3%) less than 50 years old. Older patients were more often female (35.4% vs.
      25.1% aged 18-49 years and 20.4% aged 50-74 years), white (78.7% vs. 69.4% and
      75.9%), insured (63.5% vs. 46.5% and 56.8%), and married (56.6% vs. 53% and
      51.1%), but received adequate treatment less often (72.0% vs. 86.3% and 82.7%).
      In the older cohort, male sex was associated with lower mortality (sHR: 0.92, 95%
      CI: 0.85-1.00), and unlike the younger cohorts, black race was no longer
      associated with mortality (sHR: 1.07, 95% CI: 0.94-1.22). Marriage was associated
      with lower mortality in all age groups but with diminishing effects (single sHR:
      young 1.52, middle 1.31, older 1.14). CONCLUSIONS: Elderly HNSCC patients have
      distinct effects from demographic prognostic factors and should be considered a
      separate subgroup with unique epidemiology, risks, and preferences. LEVEL OF
      EVIDENCE: 2c Laryngoscope, 2017.

PMID- 30194775
TI  - Complex decisions in the use of extracorporeal treatments in acute metformin
      overdose: which modality, when and how to measure the effect.

PMID- 30194776
TI  - Genetic susceptibility in the development of colorectal adenomas according to
      family history of colorectal cancer.
AB  - Our study aimed to evaluate the relevance of genetic susceptibility in the
      development of colorectal adenomas (CRA) and its relationship with the presence
      of family history of colorectal cancer (CRC). Genomic DNA from 750 cases (first
      degree relatives of patients with CRC) and 750 controls (subjects with no family
      history of CRC) was genotyped for 99 single nucleotide polymorphisms (SNPs)
      previously associated with CRC/CRA risk by GWAS and candidate gene studies by
      using the MassArrayTM (Sequenom) platform. Cases and controls were matched by
      gender, age and histological lesion. Eight hundred and fifty-eight patients
      showed no neoplastic lesions, whereas 288 patients showed low-risk adenomas, and
      354 patients presented high-risk adenomas. Two SNPs (rs10505477, rs6983267) in
      the CASC8 gene were associated with a reduced risk of CRA in controls (log
      additive models, OR: 0.67, 95%CI:0.54-0.83, and OR:0.66, 95%CI:0.54-0.84,
      respectively). Stratified analysis by histological lesion revealed the
      association of rs10505477 and rs6983267 variants with reduced risk of low- and
      high-risk adenomas in controls, being this effect stronger in low-risk adenomas
      (log-additive models, OR:0.63, 95%CI:0.47-0.84 and OR:0.64, 95%CI:0.47-0.86,
      respectively). Moreover, 2 SNPs (rs10795668, rs11255841) in the noncoding
      LINC00709 gene were significantly associated with a reduced risk of low-risk
      adenomas in cases (recessive models, OR:0.22, 95%CI:0.06-0.72, and OR:0.08,
      95%CI:0.03-0.61) and controls (dominant models, OR:0.50, 95%CI:0.34-0.75, and
      OR:0.52, 95%CI:0.35-0.78, respectively). In conclusion, some variants associated
      with CRC risk (rs10505477, rs6983267, rs10795668 and rs11255841) are also
      involved in the susceptibility to CRA and specific subtypes. These associations
      are influenced by the presence of family history of CRC.

PMID- 30194777
TI  - A framework for estimating the effects of sequential reproductive barriers:
      Implementation using Bayesian models with field data from cryptic species.
AB  - Determining how reproductive barriers modulate gene flow between populations
      represents a major step toward understanding the factors shaping the course of
      speciation. Although many indices quantifying reproductive isolation (RI) have
      been proposed, they do not permit the quantification of cross-direction-specific
      RI under varying species frequencies and over arbitrary sequences of barriers.
      Furthermore, techniques quantifying associated uncertainties are lacking, and
      statistical methods unrelated to biological process are still preferred for
      obtaining confidence intervals and P-values. To address these shortcomings, we
      provide new RI indices that model changes in gene flow for both directions of
      hybridization, and we implement them in a Bayesian model. We use this model to
      quantify RI between two species of the psyllid Cacopsylla pruni based on field
      genotypic data for mating individuals, inseminated spermatophores and progeny.
      The results showed that preinsemination isolation was strong, mildly asymmetric,
      and indistinguishably different between study sites despite large differences in
      species frequencies; that postinsemination isolation strongly affected the more
      common hybrid type; and that cumulative isolation was close to complete. In the
      light of these results, we discuss how these developments can strengthen
      comparative RI studies.

PMID- 30194778
TI  - The addition of lymphadenectomy to secondary cytoreductive surgery in comparison
      with bulky node resection in patients with recurrent ovarian cancer.
AB  - OBJECTIVE: To evaluate the role of full lymphadenectomy in patients with isolated
      nodal recurrence of ovarian cancer. METHODS: In a retrospective study, the data
      of women undergoing secondary cytoreduction at the National Cancer Institute,
      Milan, Italy, between January 1, 2001, and December 31, 2015, were collected and
      patients with isolated nodal recurrence were identified. Factors predicting for
      disease-free interval (DFI) and overall survival were estimated using Kaplan
      Meier survival analysis and Cox regression analysis. RESULTS: Of the 199
      consecutive patients whose data were collected, isolated nodal recurrence
      (defined as the presence of lymphatic disease) was observed in 35 women. Among
      this study cohort, lymphadenectomy and bulky node removal were performed in 11
      (31%) and 24 (69%) patients, respectively. Women who underwent lymphadenectomy
      experienced better DFI compared with those who had bulky node removal only
      (median 21 and 12 months, respectively; P=0.019), and lymphadenectomy, but not
      bulky node removal, significantly improved rates of DFI (P=0.043). No factors
      were independently associated with overall survival; however, a trend toward an
      improved overall survival rate was observed in patients undergoing complete
      resection at the time of primary surgery (P=0.055). CONCLUSION: Lymphadenectomy
      at the time of secondary cytoreduction improved DFI but did not have a
      significant effect on overall survival.

PMID- 30194780
TI  - Identification of FDA-approved drugs as novel allosteric inhibitors of human
      executioner caspases.
AB  - The regulation of apoptosis is a tightly coordinated process and caspases are its
      chief regulators. Of special importance are the executioner caspases, caspase
      3/7, the activation of which irreversibly sets the cell on the path of death.
      Dysregulation of apoptosis, particularly an increased rate of cell death lies at
      the root of numerous human diseases. Although several peptide-based inhibitors
      targeting the homologous active site region of caspases have been developed,
      owing to their non-specific activity and poor pharmacological properties their
      use has largely been restricted. Thus, we sought to identify FDA-approved drugs
      that could be repurposed as novel allosteric inhibitors of caspase-3/7. In this
      study, we virtually screened a catalog of FDA-approved drugs targeting an
      allosteric pocket located at the dimerization interface of caspase-3/7. From
      among the top-scoring hits we short-listed 5 compounds for experimental
      validation. Our enzymatic assays using recombinant caspase-3 suggested that 4 out
      of the 5 drugs effectively inhibited caspase-3 enzymatic activity in vitro with
      IC50 values ranging ~10-55 MUM. Structural analysis of the docking poses show the
      4 compounds forming specific non-covalent interactions at the allosteric pocket
      suggesting that these molecules could disrupt the adjacently-located active site.
      In summary, we report the identification of 4 novel non-peptide allosteric
      inhibitors of caspase-3/7 from among FDA-approved drugs.

PMID- 30194781
TI  - Membrane physical state and stress regulation in Synechocystis: fluidizing
      alcohols repress fatty acid desaturation.
AB  - Cyanobacteria are prokaryotic photosynthetic organisms widely used in
      biotechnology, photosynthesis and abiotic stress research. There are several
      cyanobacterial strains modified to produce biofuels, but the influence of
      alcohols on cyanobacterial cell physiology is poorly understood. Here, we
      conducted a systematic study of the effects of nine primary aliphatic alcohols
      and an aromatic benzyl alcohol on both membrane physical state and the expression
      of genes for fatty acid desaturases (FADs) in a model cyanobacterium
      Synechocystis sp. strain PCC 6803. Hexan-1-ol was found to have the most membrane
      fluidizing action among all alcohols studied, with its efficiency correlating
      with both duration of treatment and alcohol concentration. A prolonged exposure
      to alcohol results in a continuous loss of unsaturated fatty acids (FAs) followed
      by cell death, an undesired challenge that should be considered in cyanobacterial
      biotechnology. We suggest that membrane fluidization is the key component in
      alcohol stress causing inactivation of FADs and resulting in a lethal depletion
      of unsaturated FAs. Due to the most pronounced effects of alcohol- and heat
      induced membrane fluidization on desB encoding a terminal omega3-FAD, we propose
      to call desB a 'viscosity gene' in analogy to heat-induced 'fluidity gene' hspA.

PMID- 30194782
TI  - Monitoring serum cytokeratin 19 fragment 21-1 to determine the efficacy of
      docetaxel chemotherapy in advanced extramammary Paget's disease.

PMID- 30194779
TI  - Sex-dependent changes in neuroactive steroid concentrations in the rat brain
      following acute swim stress.
AB  - Sex differences in hypothalamic-pituitary-adrenal (HPA) axis activity are well
      established in rodents. In addition to glucocorticoids, stress also stimulates
      the secretion of progesterone and deoxycorticosterone (DOC) from the adrenal
      gland. Neuroactive steroid metabolites of these precursors can modulate HPA axis
      function; however, it is not known whether levels of these steroids differ
      between male and females following stress. In the present study, we aimed to
      establish whether neuroactive steroid concentrations in the brain display sex-
      and/or region-specific differences under basal conditions and following exposure
      to acute stress. Brains were collected from male and female rats killed under
      nonstress conditions or following exposure to forced swimming. Liquid
      chromatography-mass spectrometry was used to quantify eight steroids:
      corticosterone, DOC, dihydrodeoxycorticosterone (DHDOC), pregnenolone,
      progesterone, dihydroprogesterone (DHP), allopregnanolone and testosterone in
      plasma, and in five brain regions (frontal cortex, hypothalamus, hippocampus,
      amygdala and brainstem). Corticosterone, DOC and progesterone concentrations were
      significantly greater in the plasma and brain of both sexes following stress;
      however, the responses in plasma were greater in females compared to males. This
      sex difference was also observed in the majority of brain regions for DOC and
      progesterone but not for corticosterone. Despite observing no stress-induced
      changes in circulating concentrations of pregnenolone, DHDOC or DHP,
      concentrations were significantly greater in the brain and this effect was more
      pronounced in females than males. Basal plasma and brain concentrations of
      allopregnanolone were significantly higher in females; moreover, stress had a
      greater impact on central allopregnanolone concentrations in females. Stress had
      no effect on circulating or brain concentrations of testosterone in males. These
      data indicate the existence of sex and regional differences in the generation of
      neuroactive steroids in the brain following acute stress, especially for the
      5alpha-reduced steroids, and further suggest a sex-specific expression of
      steroidogenic enzymes in the brain. Thus, differential neurosteroidogenesis may
      contribute to sex differences in HPA axis responses to stress.

PMID- 30194783
TI  - Pilot study shows right ventricular diastolic function impairment in young
      children with obstructive respiratory disease.
AB  - AIM: This study determined cardiovascular impairment in young children with
      obstructive respiratory disease who were assessed using the opening interrupter
      technique (RINT). METHODS: This pilot study enrolled 41 children who had been
      referred to pulmonology and allergology specialists at the University of Catania,
      Italy, from March to July 2017: 23 (mean age 4.13 +/- 0.62 years) had chronic
      coughs and wheezing and 18 controls (mean age 4.27 +/- 0.66 years) had
      obstructive chest disease, but were otherwise healthy. Airway resistance was
      evaluated using RINT and cardiac function by studying the ejection fraction,
      pulmonary artery systolic pressure (PASP), tricuspid annular plane systolic
      excursion and tricuspid flow propagation velocity (TFPV). RESULTS: The RINT and
      PASP values were significantly higher in the patient group when compared to the
      controls, but the TFPV values were lower. A direct and significant Spearman's
      correlation coefficient (r) between RINT and PASP values was observed (r = 0.81).
      We found a significant inverse correlation between RINT and TFPV (r = -0.83), as
      well as TFPV and PASP (r = -0.78). CONCLUSION: This study showed that children
      with obstructive respiratory diseases had a major risk of cardiovascular
      impairment. Impaired diastolic function of the right ventricle occurred very
      early when airway resistance was abnormally increased.

PMID- 30194784
TI  - Diprotonation of Guanidine in Superacidic Solutions.
AB  - Guanidinium chloride reacts with the superacidic solutions HF/MF5 (M=As, Sb) at a
      molar ratio of 1:2 under formation of the diprotonated guanidinium salts [C(NH2
      )2 (NH3 )][AsF6 ]2 and [C(NH2 )2 (NH3 )][SbF6 ]2 . The compounds were
      characterized by using infrared and Raman spectroscopy. Furthermore, single
      crystal X-ray structure analysis of the guanidinium(2+) salts [C(NH2 )2 (NH3
      )][SbF6 ]2 ?HF, [C(NH2 )2 (NH3 )]2 [Ge3 F16 ]?HF, and [C(NH2 )2 (NH3 )]2 [Ge3 F16
      ]?2 HF and the guanidinium(1+) salt [C(NH2 )3 ][SbF6 ] is reported. The
      discussion of the experimental data is supported by quantum-chemical calculations
      of the [C(NH2 )2 (NH3 )]2+ and [C(NH2 )3 ]+ ions to investigate the modification
      of the resonance stabilization during the protonation process at the PBE1PBE/6
      311G++(3df,3pd) level of theory. The planar CN3 skeleton of the guanidinium(2+)
      ion has two carbon-nitrogen bonds in the range 1.286(4)-1.293(4) A and one carbon
      nitrogen bond of 1.453(4) A, which can be explained with a decreased resonance
      stabilization relative to the guanidinium(1+) ion.

PMID- 30194785
TI  - Visualization of cerebrospinal fluid dynamics using multi-spin echo acquisition
      cine imaging (MUSACI).
AB  - PURPOSE: To evaluate the visualization of CSF dynamics using the novel method
      multi-spin echo acquisition cine imaging (MUSACI). METHODS: MUSACI is based on
      multi-echo volume isotropic turbo spin-echo acquisition (VISTA) with pulse
      gating. MUSACI images were acquired in 11 healthy volunteers (7 men, 4 women; age
      range, 24-46 y, mean age, 31.9 +/- 5.51 y). We compared the CSF signal
      intensities (SIs) at multiple values of the effective echo time (TEeff ) at the
      lateral ventricle, the foramen of Monro, the third ventricle, and the fourth
      ventricle. We compared the CSF SI changes in MUSACI at multiple TEeff and the
      mean velocities in phase contrast (PC) at each trigger delay at the foramen of
      Monro, the third ventricle, and the fourth ventricle. RESULTS: The anterograde
      CSF motion from the aqueduct to the fourth ventricle, the retrograde motion from
      the aqueduct to the third ventricle, and the retrograde motion from the foramen
      of Monro to the lateral ventricle were observed with MUSACI. The CSF SIs at each
      TEeff in the foramen of Monro, the third ventricle, and the fourth ventricle were
      significantly lower than that at each TEeff in the lateral ventricle (P < 0.05).
      The CSF SI in MUSACI changed with the TEeff , and the CSF movements were observed
      at each trigger delay in PC. CONCLUSION: MUSACI can provide both high-resolution
      anatomical detail of the CSF passageways and physiologic information regarding
      CSF dynamics in a single scan.

PMID- 30194786
TI  - Effect of human breast milk on biological metabolism in infants.
AB  - The metabolic changes that occur during the postnatal weaning period appear to be
      particularly important for future health, and human breast milk is considered to
      provide the optimal source of nutrition for infants. Our previous studies
      examined the effect of feeding type on antioxidative properties, glucose and
      insulin metabolism, the lipid profile, metabolomics, and prostaglandin (PG)
      metabolism in term and preterm infants. A urinary marker of oxidative DNA damage
      (8-hydroxy-2'-deoxyguanosine) was significantly lower in breast-fed term and
      preterm infants than in formula-fed infants. Markers of insulin sensitivity were
      significantly lower and atherosclerotic indices were significantly higher in
      breast-fed preterm infants than in mixed-fed infants at discharge. On urinary
      metabolomics analysis, choline, choline metabolites, and lactic acid were
      significantly lower in breast-fed term infants than in formula-fed infants.
      Urinary PGD2 metabolite level in breast-fed term infants was also significantly
      lower than in formula-fed term infants. This indicates that human breast milk
      affects biological metabolism in early infancy.

PMID- 30194787
TI  - Room-Temperature Liquid Na-K Anode Membranes.
AB  - The Na-K alloy is a liquid at 25  degrees C over a large compositional range. The
      liquid alloy is also immiscible in the organic-liquid electrolytes of an alkali
      ion rechargeable battery, providing dendrite-free liquid alkali-metal batteries
      with a liquid-liquid anode-electrolyte interface at room temperature. The two
      liquids are each immobilized in a porous matrix. In previous work, the porous
      matrix used to immobilize the alloy was a carbon paper that is wet by the alloy
      at 420  degrees C; the alloy remains in the paper at room temperature. Here we
      report a room-temperature vacuum infiltration of the alloy into a porous Cu or Al
      membrane and a reversible stripping/plating of the liquid alloy with the
      immobilized organic-liquid electrolyte; no self-diacharge is observed since the
      liquid Na-K does not dissolve into the liquid carbonate electrolytes. The
      preparation and stripping/plating of the liquid alkali-metal anode can both now
      be done safely at room temperature.

PMID- 30194788
TI  - Ascites formation accompanied by portal vein thrombosis after porcine islet
      xenotransplantation via the portal vein in Rhesus macaque (Macaca mulatta).
AB  - Pig-to-nonhuman primate (NHP) islet transplantation has been widely conducted as
      a preclinical xenotransplantation model prior to human clinical trial. Portal
      vein thrombosis is one of the complications associated with islet infusion
      through the portal vein into the liver. Here, we briefly report severe case of
      ascites formation accompanied by portal vein thrombi after pig-to-NHP islet
      xenotransplantation in a rhesus monkey. Meticulous prophylactic treatment such as
      continuous heparin infusion should be implemented to prevent portal vein thrombi
      in pig-to-NHP islet transplantation models.

PMID- 30194789
TI  - Price elasticity of illegal versus legal cannabis: a behavioral economic
      substitutability analysis.
AB  - BACKGROUND AND AIMS: The evolving legal status of cannabis world-wide
      necessitates evidence-based regulatory policies to minimize risks associated with
      cannabis misuse. A prominent concern is the impact legalization may have on the
      illegal cannabis market, including whether illegal cannabis will serve as a
      substitute for legal cannabis. Empirical data on this issue are virtually non
      existent. This study used behavioral economics to investigate substitutability of
      legal and illegal cannabis in legalized catchment areas in the United States.
      DESIGN: A substitution-based marijuana purchase task assessed estimated cannabis
      consumption from concurrently available legal (a dispensary) and illegal (a
      dealer) sources. Prices of the two options were reciprocally either held constant
      ($10/gram) or escalated ($0-$60/gram). SETTING: US states with legalized
      recreational cannabis. PARTICIPANTS: Adult cannabis users who were at least 21
      years old (n = 724; mean age = 34.13; 52% female; 74% Caucasian) were recruited
      using online crowdsourcing. MEASUREMENTS: Mean consumption values were used in
      demand curve modeling to generate indices of price sensitivity and elasticity.
      Differences in demand indices were compared using extra sums-of-squares F-tests.
      FINDINGS: Both legal and illegal fixed-price cannabis options had significant
      positive cross-price elasticities (Ps < 0.001), indicating that higher prices
      motivate substitution irrespective of legality. However, the presence of a legal
      alternative had a substantially greater effect on consumption and elasticity of
      illegal cannabis (?elasticity  = 0.0019; F(1,37)  = 160, P < 0.0001) than the
      presence of an illegal alternative on demand for legal cannabis (?elasticity  =
      0.0002; F(1,37)  = 48, P < 0.0001), indicating asymmetric substitution. Demand
      for legal cannabis was significantly greater than for illegal cannabis (P <
      0.0001). CONCLUSIONS: Cannabis users treat legal cannabis as a superior commodity
      compared with illegal cannabis and exhibit asymmetric substitutability favoring
      legal product. Cannabis price policies that include somewhat higher consumer
      costs for legal cannabis relative to contraband (but not excessively higher
      costs) would not be expected to incentivize and expand the illegal market.

PMID- 30194790
TI  - The inhibition effect of garlic-derived compounds on human immunodeficiency virus
      type 1 and saquinavir.
AB  - Garlic has been used as a traditional medicine to treat various diseases. Garlic
      reduces the risk of some diseases. This protective effect is due to the
      organosulfur compounds of garlic. The aim of this study was to investigate the
      inhibition effects of garlic-derived compounds on human immunodeficiency virus
      type 1 (HIV-1) and as the most important anti-HIV-1 medicine. The activation of
      saquinavir is believed to be the principal mechanism behind the protective
      effects of HIV-1. Our theoretical calculations are performed for blood phase by
      using the density functional theory for the main compounds of garlic. The
      chemical activity and solubility of ajoene and the mainly derived compounds of
      garlic as theoretical calculations are important for the medical research
      comparing with the other compounds of the garlic. The theoretical calculations
      have helped us to determine which active ingredient of the garlic having
      inhibition effects on HIV-1 and saquinavir.

PMID- 30194791
TI  - A Pediatric Emergency Department Intervention to Increase Contraception
      Initiation Among Adolescents.
AB  - BACKGROUND: The pediatric emergency department (PED) provides care for
      adolescents at high risk of unintended pregnancy, but little is known regarding
      the efficacy of PED-based pregnancy prevention interventions. The objectives of
      this PED-based pilot intervention study were to 1) assess the rate of
      contraception initiation after contraceptive counseling and appointment
      facilitation in the PED during the study period, 2) identify barriers to
      successful contraception initiation, and 3) determine adolescent acceptability of
      the intervention. METHODS: This pilot intervention study included females 14 to
      19 years of age at risk for unintended pregnancy. Participants received
      standardized contraceptive counseling and were offered an appointment with
      gynecology. Participants were followed via electronic medical record and phone to
      assess contraception initiation and barriers. Chi-square tests were used to
      examine the association between contraception initiation and participant
      characteristics. RESULTS: A total of 144 patients were eligible, and 100 were
      enrolled. In the PED, 68% (68/100) expressed interest in initiating hormonal
      contraception, with 70% (48/68) of interested participants indicating that long
      acting reversible contraception (LARC) was their preferred method. Twenty-five
      percent (25/100) of participants initiated contraception during the study period,
      with 19 participants starting LARC. Thirty-nine percent (22/57) of participants
      who accepted a gynecology appointment attended that appointment. Barriers to
      follow-up include transportation and inconvenient follow-up times. Participants
      were accepting of the intervention with 93% agreeing that the PED is an
      appropriate place for contraceptive counseling. CONCLUSIONS: PED contraceptive
      counseling is acceptable among adolescents and led to successful contraception
      initiation in 25% of participants. The main barrier to contraception initiation
      was participant follow-up with the gynecology appointment.

PMID- 30194793
TI  - Interventions for dental fluorosis: A systematic review.
AB  - OBJECTIVE: Dental fluorosis has considerable implications on the patients'
      quality of life. The present study assesses the comparative effectiveness of the
      various interventions for the treatment of fluorosed enamel. MATERIALS AND
      METHODS: Nine databases were searched from inception to December 2016 for
      randomized trials. After duplicate study selection, data extraction, and risk of
      bias assessment, mean differences (MD) or Relative Risks and the corresponding
      95% confidence intervals (CIs) were calculated and assessed with the GRADE
      approach. RESULTS: Six trials with a total of 348 patients (at least 40% male/60%
      female) with a mean age of 17.7 years treated with bleaching, microabrasion, or
      resin infiltration were included. Evidence of low quality indicated that
      microabrasion resulted in smaller esthetic improvement compared to bleaching (MD
      = -2.9; 95% CI = -3.4 to -2.5). Evidence of moderate quality indicated that
      compared to bleaching a greater esthetic improvement was seen with resin
      infiltration (MD = 3.6; 95% CI = 2.7-4.6) or a combination of bleaching with
      resin infiltration (MD = 3.5; 2.8-3.7). However, all comparisons were supported
      from single trials and therefore caution is warranted. CONCLUSIONS: Based on the
      existing limited evidence, resin infiltration seems to be the most promising
      treatment for dental fluorosis, followed by bleaching and microabrasion. CLINICAL
      SIGNIFICANCE: For this systematic review, which was registered beforehand in
      PROSPERO (CRD42016053492), we synthesized evidence from existing randomized
      clinical trals on humans to see which treatment is most effective for the
      esthetic rehabilitation of dental fluorosis, the prevalence of which is seeing a
      worldwide steady increase. We found that resin infiltration seems to be the most
      effective treatment approach for lesions of mild to moderate severity, followed
      by bleaching, and finally microabrasion. Our study's strengths are its a priori
      registration, wide search, quality check according to Cochrane guidelines, and
      the use of a new robust analytic method to provide valid clinical recommendations
      according to the principles of evidence-based medicine.

PMID- 30194794
TI  - Emerging role of MRI in radiation therapy.
AB  - Advances in multimodality imaging, providing accurate information of the
      irradiated target volume and the adjacent critical structures or organs at risk
      (OAR), has made significant improvements in delivery of the external beam
      radiation dose. Radiation therapy conventionally has used computed tomography
      (CT) imaging for treatment planning and dose delivery. However, magnetic
      resonance imaging (MRI) provides unique advantages: added contrast information
      that can improve segmentation of the areas of interest, motion information that
      can help to better target and deliver radiation therapy, and posttreatment
      outcome analysis to better understand the biologic effect of radiation. To take
      advantage of these and other potential advantages of MRI in radiation therapy,
      radiologists and MRI physicists will need to understand the current radiation
      therapy workflow and speak the same language as our radiation therapy colleagues.
      This review article highlights the emerging role of MRI in radiation dose
      planning and delivery, but more so for MR-only treatment planning and delivery.
      Some of the areas of interest and challenges in implementing MRI in radiation
      therapy workflow are also briefly discussed. Level of Evidence: 5 Technical
      Efficacy: Stage 5 J. Magn. Reson. Imaging 2018;48:1468-1478.

PMID- 30194792
TI  - Girdin/GIV regulates collective cancer cell migration by controlling cell
      adhesion and cytoskeletal organization.
AB  - Pathological observations show that cancer cells frequently invade the
      surrounding stroma in collective groups rather than through single cell
      migration. Here, we studied the role of the actin-binding protein Girdin, a
      specific regulator of collective migration of neuroblasts in the brain, in
      collective cancer cell migration. We found that Girdin was essential for the
      collective migration of the skin cancer cell line A431 on collagen gels as well
      as their fibroblast-led collective invasion in an organotypic culture model. We
      provide evidence that Girdin binds to beta-catenin that plays important roles in
      the Wnt signaling pathway and in E-cadherin-mediated cell-cell adhesion. Girdin
      depleted cells displayed scattering and impaired E-cadherin-specific cell-cell
      adhesion. Importantly, Girdin depletion led to impaired cytoskeletal association
      of the beta-catenin complex, which was accompanied by changes in the
      supracellular actin cytoskeletal organization of cancer cell cohorts on collagen
      gels. Although the underlying mechanism is unclear, this observation is
      consistent with the established role of the actin cytoskeletal system and cell
      cell adhesion in the collective behavior of cells. Finally, we showed the
      correlation of the expression of Girdin with that of the components of the E
      cadherin complex and the differentiation of human skin cancer. Collectively, our
      results suggest that Girdin is an important modulator of the collective behavior
      of cancer cells.

PMID- 30194795
TI  - Desert leaf litter decay: Coupling of microbial respiration, water-soluble
      fractions and photodegradation.
AB  - The mechanisms of plant litter decay in drylands are poorly understood, limiting
      the accuracy of nutrient-cycling models for these systems. We monitored the decay
      of 12 leaf litter types on the soil surface of the Sonoran Desert for 34 months
      and assessed what traits predicted mass loss and how exposure to different
      wavebands of sunlight influenced mass loss. Mass loss varied considerably among
      litter types, ranging from 42%-96% after 34 months in full sunlight. Traditional
      indices of litter quality (e.g., initial C:N or lignin:N ratios) failed to
      predict differences in mass loss among litter types. The strongest predictor of
      mass loss was the microbial respiration rate of initial litter, which explained
      45%-54% of the variation in loss among litter types. Microbial respiration rates
      were not correlated with traditional indices of litter quality, but were
      positively correlated with the water-soluble fraction in litter and
      concentrations of dissolved organic C in this fraction. Traditional indices of
      litter quality failed to predict decay likely because they did a poor job of
      predicting microbial degradability of litter, not because microbial degradation
      was a minor driver of decay. In all radiation-exposure treatments, water-soluble
      fractions and respiration rates increased through decay and were several times
      higher after 34 months than initially. Hence, labile pools and microbial
      degradability of litter increased through decay in contrast to traditional views
      that labile pools decline and constrain microbes. Litter exposed to UV or UV
      through blue radiation wavelengths, lost on average 1.3 times or 1.5 times more
      mass, respectively, than litter not exposed to these wavebands. The magnitude of
      this photodegradation was greater in litter types that had higher initial
      concentrations of hemicellulose and cellulose per unit surface area. Litter
      exposed to full sun had higher water-soluble fractions and usually had higher
      respiration rates, illustrating that sunlight accelerated microbial degradation
      by increasing labile pools. The processes driving litter decay appeared to differ
      appreciably from mesic systems and involved strong couplings between abiotic and
      biotic drivers.

PMID- 30194796
TI  - Efficacy of omalizumab in severe chronic spontaneous urticaria: Real life data
      from a Greek tertiary center.

PMID- 30194798
TI  - Factors influencing experimental estimation of scavenger removal and observer
      detection in bird-window collision surveys.
AB  - Wildlife collisions with human-built structures are a major source of direct
      anthropogenic mortality. Understanding and mitigating the impact of anthropogenic
      collisions on wildlife populations require unbiased mortality estimates. However,
      counts of collision fatalities are underestimated due to several bias sources,
      including scavenger removal of carcasses between fatality surveys and imperfect
      detection of carcasses present during surveys. These biases remain particularly
      understudied for bird-window collisions, the largest source of avian collision
      mortality. In Stillwater, Oklahoma, USA, we used bird carcasses collected during
      window collision monitoring to experimentally assess factors influencing
      scavenging and observer detection, and we employed trail cameras to characterize
      the scavenger community and timing of scavenging. We recorded nine scavenger
      species, but the domestic cat and Virginia opossum were responsible for 73% of
      known-species scavenging events. The most frequent scavenger species were
      primarily nocturnal, and 68% of scavenging events occurred at night. Scavenger
      species best predicted time to first scavenging event, season best predicted
      carcass persistence time, and both season and carcass size predicted whether any
      carcass remains persisted after scavenging. Our results also suggest that
      observer detection was influenced by substrate, with greater detection of
      carcasses on artificial substrates. Our findings related to scavenging timing
      have important implications for the unbiased estimation of collision mortality
      because the timing of peak scavenging relative to timing of peak mortality can
      substantially influence accuracy of adjusted mortality estimates. Further, the
      differences in correlates for time to first scavenging and time to carcass
      removal (i.e., persistence time) illustrate the importance of explicitly
      measuring these often-independent events that are frequently conflated in the
      anthropogenic mortality literature.

PMID- 30194797
TI  - Brain active transmembrane water cycling measured by MR is associated with
      neuronal activity.
AB  - PURPOSE: fMRI is widely used to study brain activity. Unfortunately, conventional
      fMRI methods assess neuronal activity only indirectly, through hemodynamic
      coupling. Here, we show that active, steady-state transmembrane water cycling
      (AWC) could serve as a basis for a potential fMRI mechanism for direct neuronal
      activity detection. METHODS: AWC and neuronal actitivity in rat organotypic
      cortical cultures were simultaneously measured with a hybrid MR-fluorescence
      system. Perfusion with a paramagnetic MRI contrast agent, Gadoteridol, allows NMR
      determination of the kinetics of transcytolemmal water exchange. Changes in
      intracellular calcium concentration, [Cai2+ ] were used as a proxy of neuronal
      activity and were monitored by fluorescence imaging. RESULTS: When we alter
      neuronal activity by titrating with extracellular [K+ ] near the normal value, we
      see an AWC response resembling Na+ -K+ -ATPase (NKA) Michaelis-Menten behavior.
      When we treat with the voltage-gated sodium channel inhibitor, or with an
      excitatory postsynaptic inhibitor cocktail, we see AWC decrease by up to 71%. AWC
      was found also to be positively correlated with the basal level of spontaneous
      activity, which varies in different cultures. CONCLUSIONS: These results suggest
      that AWC is associated with neuronal activity and NKA activity is a major
      contributor in coupling AWC to neuronal activity. Although AWC comprises steady
      state, homeostatic transmembrane water exchange, our analysis also yields a
      simultaneous measure of the average cell volume, which reports any slower net
      transmembrane water transport.

PMID- 30194799
TI  - Characteristics of NSAID-induced hypersensitivity reactions in childhood.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) are available as over-the-counter
      drugs, and they are commonly used in children for their antipyretic, analgesic,
      and anti-inflammatory effects. NSAIDs are among the most frequently reported
      drugs associated with hypersensitivity reactions and even with anaphylaxis. A
      complete evaluation of the patients based on reported clinical manifestations,
      timing of the reaction, the presence of underlying disease, and reactions to
      other NSAIDs allows clinicians to stratify children with a history of reaction to
      NSAIDs. Although NSAID-induced hypersensitivity reactions have mainly been
      investigated in adults, recent studies have aimed to explore their epidemiology
      in the pediatric population. This review will cover the current understanding of
      clinical manifestations, the risk factors, and the different phenotypes of NSAID
      induced hypersensitivity reactions with a comprehensive overview of the
      epidemiologic data from past to present and the practical approach to the
      management of NSAID hypersensitivity in children and adolescents.

PMID- 30194800
TI  - Cre/lox-controlled spatiotemporal perturbation of FGF signaling in zebrafish.
AB  - BACKGROUND: Spatiotemporal perturbation of signaling pathways in vivo remains
      challenging and requires precise transgenic control of signaling effectors.
      Fibroblast growth factor (FGF) signaling guides multiple developmental processes,
      including body axis formation and cell fate patterning. In zebrafish, mutants and
      chemical perturbations affecting FGF signaling have uncovered key developmental
      processes; however, these approaches cause embryo-wide perturbations, rendering
      assessment of cell-autonomous vs. non-autonomous requirements for FGF signaling
      in individual processes difficult. RESULTS: Here, we created the novel transgenic
      line fgfr1-dn-cargo, encoding dominant-negative Fgfr1a with fluorescent tag under
      combined Cre/lox and heatshock control to perturb FGF signaling spatiotemporally.
      Validating efficient perturbation of FGF signaling by fgfr1-dn-cargo primed with
      ubiquitous CreERT2, we established that primed, heatshock-induced fgfr1-dn-cargo
      behaves similarly to pulsed treatment with the FGFR inhibitor SU5402. Priming
      fgfr1-dn-cargo with CreERT2 in the lateral plate mesoderm triggered selective
      cardiac and pectoral fin phenotypes without drastic impact on overall embryo
      patterning. Harnessing lateral plate mesoderm-specific FGF inhibition, we
      recapitulated the cell-autonomous and temporal requirement for FGF signaling in
      pectoral fin outgrowth, as previously inferred from pan-embryonic FGF inhibition.
      CONCLUSIONS: As a paradigm for rapid Cre/lox-mediated signaling perturbations,
      our results establish fgfr1-dn-cargo as a genetic tool to define the
      spatiotemporal requirements for FGF signaling in zebrafish. Developmental
      Dynamics 247:1146-1159, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 30194801
TI  - 5-Phenylcoumarin Derivatives: Design, Synthesis, and Vasodilatory Activity.
AB  - In continuation of our previous efforts towards the development of coumarin
      derivatives with potential vasodilatory activity, 5-phenylcoumarin derivatives
      were designed and synthesized. Target compounds and their precursors exhibited
      moderately vasodilatory ability with EC50 at 2.5-49.0 MUm. Docking studies also
      revealed the good binding mode of 7-methoxy-8-[2-(pyrrolidin-1-yl)ethoxy]-5-[2
      (trifluoromethyl)phenyl]-2H-chromen-2-one (8c) with the target protein. Moreover,
      intermediates and the final products exhibited different fluorescent properties
      due to their substituent effect. These results may provide new ideas for the
      synthesis and application of 5-substituted coumarins.

PMID- 30194802
TI  - Rapid discovery and global characterization of multiple components in corn silk
      using a multivariate data processing approach based on UHPLC coupled with
      electrospray ionization/quadrupole time-of-flight mass spectrometry.
AB  - Corn silk is an important traditional Chinese medicine which has been widely used
      as diuretic, antilithiasic, uricosuric, antiseptic, etc. for thousands of years.
      However, it is a pity that the chemical ingredients in corn silk, especially the
      constituents absorbed into blood, are unclear up to now. The aim of our study was
      to investigate the multiple components of corn silk in vitro and in vivo. In this
      present study, a sensitive and rapid method using ultra high performance liquid
      chromatography coupled with electrospray ionization/quadrupole time-of-flight
      tandem mass spectrometry and a multivariate data processing approach was
      established to detect the constituents of corn silk in vitro and in vivo.
      Consequently, total 41 ingredients in vitro and 19 of them absorbed into blood
      including luteolin, various C-glycosyl flavones, jasmonic acid, abscisic acid,
      gibberellin A, etc. were tentatively characterized in sequence. Furthermore, of
      particular importance, a kind of stable compound named C-glycosyl flavones is a
      great discovery in vivo, which can point the further pharmacological study target
      in future. In a word, this is the first serum pharmacochemistry study of corn
      silk, which played a critical role in exploring the pharmacological and effective
      data for further research.

PMID- 30194804
TI  - The World Health Organization Code and exclusive breastfeeding in China, India,
      and Vietnam.
AB  - Promoting exclusive breastfeeding (EBF) is a highly feasible and cost-effective
      means of improving child health. Regulating the marketing of breastmilk
      substitutes is critical to protecting EBF. In 1981, the World Health Assembly
      adopted the World Health Organization International Code of Marketing of
      Breastmilk Substitutes (the Code), prohibiting the unethical advertising and
      promotion of breastmilk substitutes. This comparative study aimed to (a) explore
      the relationships among Code enforcement and legislation, infant formula sales,
      and EBF in India, Vietnam, and China; (b) identify best practices for Code
      operationalization; and (c) identify pathways by which Code implementation may
      influence EBF. We conducted secondary descriptive analysis of available national
      level data and seven high level key informant interviews. Findings indicate that
      the implementation of the Code is a necessary but insufficient step alone to
      improve breastfeeding outcomes. Other enabling factors, such as adequate
      maternity leave, training on breastfeeding for health professionals, health
      systems strengthening through the Baby Friendly Hospital Initiative, and
      breastfeeding counselling for mothers, are needed. Several infant formula
      industry strategies with strong conflict of interest were identified as harmful
      to EBF. Transitioning breastfeeding programmes from donor-led to government-owned
      is essential for long-term sustainability of Code implementation and enforcement.
      We conclude that the relationships among the Code, infant formula sales, and EBF
      in India, Vietnam, and China are dependent on countries' engagement with
      implementation strategies and the presence of other enabling factors.

PMID- 30194803
TI  - Re-evaluation of mouse tissue factor pathway inhibitor and comparison of mouse
      and human tissue factor pathway inhibitor physiology.
AB  - Essentials Mouse models are often used to define roles of tissue factor pathway
      inhibitor (TFPI) in man. TFPI isoform-specific KOs reveal unexpected differences
      between mouse and human TFPI physiology. Mouse plasma contains 20 times more TFPI
      than man, derived from TFPIgamma, a form not found in man. TFPIgamma null mice,
      expressing only TFPI isoforms alpha and beta, may better reflect the human
      situation. SUMMARY: Background Mouse models can provide insight into the
      pathophysiology of human thrombosis and hemostasis. Tissue factor pathway
      inhibitor (TFPI) regulates coagulation through protein S (PS)-enhanced factor (F)
      Xa inhibition and FXa-dependent inhibition of FVIIa/tissue factor (TF) activity.
      TFPI is expressed as isoforms alpha and beta in man, and alpha, beta and gamma in
      the mouse. Objective Assess the reliability of extending TFPI-related studies in
      mice to humans. Method Compare mouse and human TFPI physiology using a variety of
      methods. Results Mouse TFPI and human TFPI are similar in regard to: (i) the
      mechanisms for FVIIa/TF and FXa inhibition; (ii) TFPIalpha is a soluble form and
      TFPIbeta is glycosyl phosphatidyl inositol (GPI) membrane anchored; (iii) the
      predominant circulating form of TFPI in plasma is lipoprotein-associated; (iv)
      low levels of TFPIalpha circulate in plasma and increase following heparin
      treatment; and (v) TFPIalpha is the isoform in platelets. They differ in that:
      (i) mouse TFPI circulates at a ~20-fold higher concentration; (ii) mouse lines
      with isolated isoform deletions show this circulating mouse TFPI is derived from
      TFPIgamma; (iii) sequences homologous to the mouse TFPIgamma exon are present in
      many species, including man, but in primates are unfavorable for splicing; and
      (iv) tandem mass spectrometry (MS/MS) detects sequences for TFPI isoforms alpha
      and beta in human plasma and alpha and gamma in mouse plasma. Conclusion To
      dissect the pathophysiological roles of human TFPIalpha and TFPIbeta, studies in
      TFPIgamma null mice, expressing only alpha and beta, only alpha or only beta
      should better reflect the human situation.

PMID- 30194805
TI  - A novel ASPH variant extends the phenotype of Shawaf-Traboulsi syndrome.
AB  - Shawaf-Traboulsi syndrome (or Traboulsi syndrome; MIM 601552) is an infrequently
      reported entity characterized by a typical face (long face, large nose, convex
      nasal ridge, underdeveloped malae, crowded teeth, retrognathia), skeletal signs
      (long and slender fingers, sometimes pectus deformation and hypermobile joints),
      and ectopia lentis with conjunctival blebs, shallow anterior chamber and
      iridocorneal adhesions. The entity is caused by homozygous variants in ASPH.
      Here, we report on a boy with the clinical diagnosis of Shawaf-Traboulsi
      syndrome, in whom exome sequencing allowed identification of a novel variant in
      ASPH. We compare the findings in the present patient to those of earlier reported
      patients; furthermore add new signs for this entity.

PMID- 30194806
TI  - Potential need for expanded pharmacologic treatment and lifestyle modification
      services under the 2017 ACC/AHA Hypertension Guideline.
AB  - Application of the 2017 ACC/AHA Hypertension Guideline expands the number of US
      adults requiring blood pressure (BP) management. The authors use 2011-2014 NHANES
      data to describe the population groups most affected by the new guideline,
      compared with the previous JNC-7 guideline, and describe the previous interaction
      with the health care sector among those adults recommended new or intensified
      pharmacologic treatment and/or lifestyle modification. The 2017 Hypertension
      Guideline reclassifies 32.3 million US adults as newly hypertensive and
      recommends BP-related treatment of 133.7 million adults, including 57.8 million
      with uncontrolled BP recommended to initiate or intensify pharmacologic treatment
      and 50.5 million newly recommended lifestyle modification alone. An estimated
      13.1 million (22.7%) adults recommended to initiate or intensify pharmacologic
      treatment, and 20.6 million (40.8%) adults newly recommended lifestyle
      modification alone report not having established health care linkages. Among the
      adults newly recommended lifestyle modification alone, the odds of
      reclassification from no recommended intervention, under JNC-7, to recommended
      lifestyle modification alone were lower for adults with established linkages to
      care (aOR: 0.78 [95% CI: 0.67-0.91]) compared to those without, decreased with
      increasing age, were greater for men (1.72 [1.52-1.94]) compared to women and
      were greater for obese adults (1.23 [1.00-1.53]) compared with normal or
      underweight adults. Application of the 2017 Hypertension Guideline increases the
      number and alters the distribution of US adults in need of initiating or
      intensifying BP treatment. This includes identifying millions of US adults who
      previously had limited interaction with health care and are now recommended new
      or intensified pharmacologic treatment and/or lifestyle modification.

PMID- 30194807
TI  - Genomic detection of a familial 382 Kb 6q27 deletion in a fetus with isolated
      severe ventriculomegaly and her affected mother.
AB  - Terminal deletions of the chromosome 6q27 region are rare genomic abnormalities,
      linked to specific brain malformations and other neurological phenotypes.
      Reported cases have variable sized genomic deletions that harbor several genes
      including the DLL1 and TBP. We report on an inherited 0.38 Mb terminal deletion
      of chromosome 6q27 in a 22-week fetus with isolated bilateral ventriculomegaly
      and her affected mother using microarray-based comparative genomic hybridization
      and fluorescent in situ hybridization (FISH). The deleted region harbors at least
      seven genes including DLL1 and TBP. The affected mother had a history of
      hydrocephalus, developmental delay, and seizures commonly associated with DLL1
      and TBP 6q27 deletions. This deletion is one of the smallest reported isolated
      6q27 terminal deletions. Our data provides additional evidence that
      haploinsufficiency of the DLL1 and TBP genes may be sufficient to cause the
      ventriculomegaly, seizures, and developmental delays associated with terminal
      6q27 deletions, indicating a plausible role in the abnormal development of the
      central nervous system.

PMID- 30194808
TI  - Cell Therapy for Heart Regeneration: Learning from the Past to Build a Brighter
      Future.

PMID- 30194809
TI  - Sample preparation for the analysis of fire debris - Past and present.
AB  - Identification of ignitable liquids from fire debris is such a major part of an
      arson investigation that much time and effort has gone into advancing sample
      preparation techniques to capture complicated and unexpected hydrocarbon
      compounds. Advancements in sample preparation have been made in order to account
      for biodegradation of commonly used accelerants, rarely encountered compounds,
      such as vegetable oils, biodiesel, and alcohols. Improvements have also been made
      to manage interference from the sample matrix, particularly with regards to new
      materials. This paper is a review of the sample preparation techniques that are
      foundational to fire debris analysis as well as recent advances. Also explored
      are modifications to the traditional sample preparation methods to accommodate
      the analysis of environmental samples (soil and water), and the presence of
      vegetable oils and biofuels on the fire scene.

PMID- 30194810
TI  - Zirconium(IV)-based metal-organic frameworks (UiO-67) as solid-phase extraction
      adsorbents for extraction of phenoxyacetic acid herbicides from vegetables.
AB  - A zirconium(IV)-based metal organic framework, composed of 4,4'
      biphenyldicarboxylic acid ligands and Zr6 O4 (OH)4 clusters, was successfully
      fabricated. Characterizations were performed on fourier transform infrared
      spectroscopy, scanning electron microscopy, X-ray diffraction, Brunauer-Emmett
      Teller, and thermogravimetric analysis, which confirmed that it possessed large
      specific surface area, high pore volume, and strong acid resistant stability.
      Furthermore, the prepared material containing biphenyl skeleton and a large
      number of Zr-O bonds, can grasp acid herbicides especially phenoxyacetic acid
      herbicides with aromatic structures through pi-pi interaction, hydrophobic
      interaction and Zr-O-H+ bonds. Based on these advantages, a method was developed
      for the determination of four phenoxyacetic acid herbicides from vegetable
      samples. Under the optimal conditions, wide linearities from 0.3 to 250 MUg/L and
      low limits of detection from 0.1 to 0.5 MUg/L were obtained. The intra- and
      interday relative standard deviations were 1.56-3.92 and 5.01-7.65%,
      respectively. The proposed method was applied to analyze phenoxyacetic acid
      herbicides residues in the tomato, cucumber, and white gourd samples. The
      satisfactory recoveries (86.12-103.44%) for the spiked samples in vegetable
      samples were achieved which demonstrated the method was an efficient pretreatment
      procedure and has a potential application for the trace determination of
      phenoxyacetic acids from a complex matrix.

PMID- 30194811
TI  - Prevalence and predictors of exclusive breastfeeding among immigrant and Canadian
      born Chinese women.
AB  - Breastfeeding is the optimal method for infant feeding, yet migrant women may be
      at risk for suboptimal exclusivity rates. In a cohort of immigrant and Canadian
      born Chinese women, our objectives were to (a) describe patterns and prevalence
      of exclusive breastfeeding at 1, 3, and 6 months postpartum; (b) identify risk
      and protective factors associated with exclusivity; and (c) examine potentially
      differential importance of these factors across this 6-month period. This was a
      prospective study of 565 immigrants and Canadian-born Chinese women (Toronto,
      Canada). Exclusive breastfeeding was measured at 1, 3, and 6 months postpartum.
      Predictors comprised fixed (demographics, history of depression, immigrant
      status, prenatal breastfeeding classes, in-hospital formula supplementation,
      baseline social support, and baseline acculturative stress) and time-dependent
      (depression, anxiety, fatigue, and breastfeeding problems) variables. Descriptive
      statistics, logistic regression, and generalized linear mixed models,
      respectively, were undertaken to address the objectives. Patterns of
      breastfeeding practices included exclusive breastfeeding in all time points
      (26.8%) or none (32.9%) and moving from exclusive to nonexclusive (20.3%) or
      nonexclusive to exclusive breastfeeding (15.2%). Women less likely to breastfeed
      exclusively at 1, 3, or 6 months were those whose infants received in-hospital
      formula supplementation. Exclusivity attrition was higher between 3 and 6 months
      than 1-3 months. Immigrant status and in-hospital formula supplementation had a
      significant impact on exclusivity earlier in the postpartum period while
      breastfeeding problems were associated with decreased exclusivity across time.
      Proactive preventive efforts are need to maintain breastfeeding exclusivity
      especially between 3 and 6 months if women are to meet international
      breastfeeding recommendations.

PMID- 30194812
TI  - The Sociolinguistic Repetition Task: A New Paradigm for Exploring the Cognitive
      Coherence of Language Varieties.
AB  - Sociolinguistic studies generally focus on specific sociolinguistic variables.
      Consequently, they rarely examine whether different sociolinguistic variables
      have coherent orientation in a specific language variety (a social or a regional
      dialect) or whether the speakers freely mix sociolinguistic variants. While
      different attempts have been made to identify coherence and mixing in the
      production or perception of dialects, our aim is to answer this question at the
      level of the cognitive representation of varieties. For this purpose, we draw on
      the phenomenon of sociolinguistic restoration: when they repeat
      sociolinguistically mixed utterances, people tend to make them homogeneous. The
      first experiment-a repetition task-reproduced sociolinguistic restoration in an
      experimental setting. The second experiment-a judgment task-ensured that
      participants perceived the difference between homogeneous and mixed utterances.
      We conclude that high-order coherent representations influence the reconstruction
      of utterances during the repetition task.

PMID- 30194813
TI  - Clinical inertia and the 2017 ACA/AHA guideline.

PMID- 30194814
TI  - MUAC as the sole discharge criterion from community-based management of severe
      acute malnutrition in Burkina Faso.
AB  - The use of mid upper arm circumference (MUAC) measurement to screen and determine
      eligibility for admission to therapeutic feeding programs has been established,
      but evidence and programmatic experience to inform guidance on the use of MUAC as
      a discharge criterion is limited. We present results from a large-scale
      nutritional program using MUAC for admission and discharge and compare program
      outcomes and response to treatment when determining eligibility for discharge by
      proportional weight gain versus discharge by MUAC. The study population included
      all children admitted to the Ministry of Health therapeutic feeding program
      supported by Medecins Sans Frontieres in northern Burkina Faso from September
      2007 to December 2011 (n = 50,841). Recovery was high overall using both
      discharge criteria, with low risks of death, nonresponse, and transfer to
      inpatient care and high daily gains in weight, MUAC, weight-for-height Z score,
      and height. When discharge was made by MUAC only, recovery increased, while all
      adverse program outcomes and length of stay decreased, with increasing MUAC on
      admission. MUAC-based programming, where MUAC is integrated into program
      screening, admission, and discharge, is one of several new approaches that can be
      used to target resources to the most at-risk malnourished children and improve
      program efficiency and coherency. This analysis provides additional programmatic
      experience on the use of MUAC-based discharge criterion, but more work may be
      needed to inform optimal discharge thresholds across settings.

PMID- 30194815
TI  - Current Status and Future Challenges of Liver Transplantation Programs in Chile.
AB  - Liver transplantation (LT) was performed for the first time in Chile in 1969, but
      only since the 1990s has it been systematically performed. Our health system is
      strongly centralized, which is a severe limitation for the patients who need to
      be evaluated and subsequently listed. Although proper human and technological
      resources are available and our results are comparable to international outcomes
      (overall patient survival at 1, 5, and 10 years of 82%, 70%, and 64%,
      respectively), we are limited because of a severe scarcity of grafts, which
      translates into an availability of approximately 7 organs per million persons and
      a wait-list dropout rate of 40% every year. Thus, our main challenge for the next
      few years is to improve access to LT among the populations from the extreme
      regions of the country and overall to improve the availability of grafts by
      increasing the awareness of physicians in intensive care units and emergency
      departments, to develop living donor LT programs, to educate the population in
      order to decrease family refusal, and to reinforce the system of potential donor
      detection. Although hard work is mandatory for these improvements, none of these
      tasks seem to be unreachable in the midterm.

PMID- 30194816
TI  - LAMP2 exon-copy number variations in Danon disease heterozygote female probands:
      Infrequent or underdetected?
AB  - Danon disease (DD) is an X-linked disorder caused by mutations in the lysosomal
      associated membrane protein 2 (LAMP2) gene (Xq24). DD is characterized by
      cognitive deficit, myopathy, and cardiomyopathy in male patients. The phenotype
      is variable and mitigated in females. The timely identification of de-novo LAMP2
      mutated family members, many of whom are heterozygous females, remains critical
      for their treatment and family counseling. DD laboratory testing builds on
      minimally invasive quantification of the LAMP2 protein in white blood cells and
      characterization of the specific mutation. This integrative approach is
      particularly helpful when assessing suspect female heterozygotes. LAMP2 exon-copy
      number variations (eCNVs) were so far reported only in X-hemizygous male DD
      probands. In heterozygous female DD probands, the wild-type allele may hamper the
      identification of an eCNV even if it results in the complete abolition of LAMP2
      transcription and/or translation. To document the likely underappreciated rate of
      occurrence and point out numerous potential pitfalls of detection of the LAMP2
      eCNVs, we present the first two DD heterozygote female probands who harbor novel
      multi-exon LAMP2 deletions. Critical for counseling and recurrence prediction, we
      also highlight the need to search for somatic-germinal mosaicism in DD families.

PMID- 30194817
TI  - Postharvest metabolomic changes in Pyrus ussuriensis Maxim. wild accession
      'Zaoshu Shanli'.
AB  - There are strong economic drivers for understanding the process of fruit post
      harvest softening. In this study, liquid chromatography with electrospray
      ionization tandem mass spectrometry was used to analyze metabolite changes in
      'Zaoshu Shanli' fruit after different storage periods; this wild accession of
      Pyrus ussuriensis presents good fruit quality and relatively low flesh firmness
      after fruit storage. The lipid metabolites in 'Zaoshu Shanli' fruit were
      significantly higher at 18 days of storage compared with those at 0 days of
      storage, and glycerophospholipid metabolism was different metabolic pathway. It
      was therefore speculated that lipid metabolism play an important role in pear
      fruit post-harvest processes and softening. Furthermore, the abscisic acid and
      trans-zeatin contents in 'Zaoshu Shanli' fruit at 18 days of storage were
      significantly greater than those at 0 days of storage. Therefore, it was
      speculated that the abovementioned hormones play an important role in pear fruit
      post-harvest softening. Together, these results provide fundamental insight into
      the reasonable control of pear fruit post-harvest softening and lay a solid
      foundation for additional research.

PMID- 30194819
TI  - Cellular senescence, geroscience, cancer and beyond.

PMID- 30194818
TI  - Refining the phenotype associated with GNB1 mutations: Clinical data on 18 newly
      identified patients and review of the literature.
AB  - De novo germline mutations in GNB1 have been associated with a neurodevelopmental
      phenotype. To date, 28 patients with variants classified as pathogenic have been
      reported. We add 18 patients with de novo mutations to this cohort, including a
      patient with mosaicism for a GNB1 mutation who presented with a milder phenotype.
      Consistent with previous reports, developmental delay in these patients was
      moderate to severe, and more than half of the patients were non-ambulatory and
      nonverbal. The most observed substitution affects the p.Ile80 residue encoded in
      exon 6, with 28% of patients carrying a variant at this residue. Dystonia and
      growth delay were observed more frequently in patients carrying variants in this
      residue, suggesting a potential genotype-phenotype correlation. In the new cohort
      of 18 patients, 50% of males had genitourinary anomalies and 61% of patients had
      gastrointestinal anomalies, suggesting a possible association of these findings
      with variants in GNB1. In addition, cutaneous mastocytosis, reported once before
      in a patient with a GNB1 variant, was observed in three additional patients,
      providing further evidence for an association to GNB1. We will review clinical
      and molecular data of these new cases and all previously reported cases to
      further define the phenotype and establish possible genotype-phenotype
      correlations.

PMID- 30194821
TI  - Improved Knowledge Following an Interprofessional Interpreter-Use Training.
AB  - INTRODUCTION: Language barriers between patients and their healthcare providers
      are associated with negative outcomes. One approach to bridge language
      discordance is to offer interpreter-use training. This study's purpose was to
      evaluate the effects of an interprofessional interpreter-use training on speech
      language pathology (SLP), doctor of physical therapy (DPT), and master of
      occupational therapy (MOT) students. METHODS: Seventy-one students (18 SLP, 32
      DPT, and 21 MOT) participated. Participants first completed an online module and
      then participated in a 3-hour interprofessional training consisting of lecture,
      role-play, and reflection. Each completed an interpreter-use knowledge assessment
      and the Readiness for Interprofessional Learning Scale (RIPLS) before and after
      training and a program evaluation. A subsample participated in focus groups and
      completed the interpreter-use knowledge assessment and RIPLS 5 months later.
      RESULTS: The participants improved in interpreter-use knowledge and self-assessed
      readiness for interprofessional learning, and they maintained these gains at
      follow-up. Themes included new interpreter knowledge, ethical practice, and new
      interprofessional knowledge. CONCLUSION: The training was completed in a short
      period of time at no financial cost, possibly making the structure feasible for
      other educators to duplicate. A unique element of our training was the semi
      structured reflection questions highlighting ethical complexities related to
      serving as untrained interpreters for others.

PMID- 30194820
TI  - Role of Strain Elastography and Shear-Wave Elastography in a Multiparametric
      Clinical Approach to Indeterminate Cytology Thyroid Nodules.
AB  - BACKGROUND In thyroid nodules with indeterminate cytology, further clinical
      assessment aimed at ruling out malignancy is often mandatory. Ancillary imaging
      techniques and genetic mutation analysis can improve the risk stratification of
      such lesions, thereby facilitating the clinician's decision to undertaken surgery
      or simple follow-up. The aim of this study was to evaluate the diagnostic
      performance of shear-wave elastography (SW), strain elastography (ELX 2/1),
      conventional ultrasound (US), contrast-enhanced ultrasound (CEUS), and BRAF V600E
      mutation analysis in the aforementioned lesions. MATERIAL AND METHODS We enrolled
      81 patients, each with 1 indeterminate-cytology thyroid nodule. Thyroid function,
      thyroperoxidase antibodies and calcitonin were known in each case. SW, ELX 2/1,
      US, CEUS, and BRAF mutation analysis were subsequently performed, followed by a
      second FNAB. If the lesion was not downgraded to benign, surgery was recommended
      and histological reports collected. RESULTS There were 28 nodules (34%) that
      proved benign on the second FNAB; 38 nodules (47%) underwent surgery (17 benign,
      21 malignant), and 15 nodules (19%) refused surgery. The only techniques related
      to histological outcome were US (AUC=0,766), ELX 2/1 (AUC=0.701), and BRAF
      analysis (AUC=0.762). ELX 2/1 and SW reports were not correlated with each other
      (P=0.45). A scoring system taking into account all the variables considered
      performed better than the single variables alone (AUC=0.831). CONCLUSIONS In
      indeterminate-cytology thyroid lesions, repeating FNAB can avoid unnecessary
      surgery. ELX 2/1 seems to perform better than SW in distinguishing malignancy;
      these techniques could, however, be complementary in describing such lesions. A
      multiparametric approach appears the most accurate in predicting nodule
      histology.

PMID- 30194822
TI  - A Personal Experience of Performing a Systematic Literature Review.
AB  - This paper describes the personal experience of two novice reviewers in
      developing and conducting a systematic litera!ture review (SLR) in the field of
      medical ultrasound. The review was performed as part of a PhD study by the first
      author, which required the researcher to critically review all relevant studies
      in their specific research area. The review was conducted using a formal,
      scientific process and high!lighted 20 relevant papers. Among the lessons learnt,
      undertaking an SLR was a time-consuming process. The search produced 1,987
      papers, and screening the search yield was facilitated by using a pre-defined
      protocol. Extraction of data from each study was standardised and generated a 1
      page summary of the key findings and methodology to facilitate comparisons of the
      included studies. The Critical Appraisal Skills Programme (CASP) tool was used
      for quality assessment. In the critical appraisal process, it is essential that
      reviewers have good baseline knowledge in the research subject, a solid
      under!standing of the fundamentals of a robust research study including potential
      bias in research. With the great amount of information that a critical appraisal
      produces, good information management was key throughout the review to ensure the
      process was explicit and replicable and so that reviewers could justify their
      decisions. The methods and processes detailed in this report, as well as its
      lessons, are relevant to an SLR for any research subject.

PMID- 30194823
TI  - A Qualitative Study on the Usage of a Learning Management System by Allied Health
      Faculty.
AB  - Learning management systems (LMSs) are available to faculty in many higher
      education institutions; however, not all faculty members take advantage of the
      tools LMSs offer in facilitating their face-to-face classes. To deepen
      understanding of this gap, this study explored faculty's experiences in LMS usage
      and factors that affected faculty's use of LMS to facilitate classroom learning.
      For this qualitative study, data were collected through interviews with various
      allied health faculty (n=10), and content analysis was used to identify themes.
      Two types of LMS user groups were identified in the study: high LMS users, who
      used three or more LMS tools, and low LMS users, who used fewer tools. Data
      analysis for the high LMS users identified four themes: adopted andragogy,
      perceived usefulness, perceived ease of use, and enhances adopted andragogy. For
      low LMS users, five themes were developed: no adopted andragogy, perceived
      usefulness, perceived ease of use, work enhancement, and barriers for further
      use. Both groups had the themes of perceived usefulness and perceived ease of
      use, but to various degrees. The emergent themes imply that high LMS users had an
      adopted andragogy framework from which they worked in designing their face-to
      face courses, but low LMS users did not. Having an adopted andragogy appears to
      motivate faculty to use LMSs beyond the basic tools. The results of this
      qualitative study extended the technology acceptance model, an information
      systems theory explaining how users accept and use technology by adding a pivotal
      preceding construct, adopted andragogy, which is faculty embracing methods for
      teaching adult learners.

PMID- 30194824
TI  - Professional Values Are Implicit in Written Reflections by DPT Students in a
      Short-Term International Service Learning Course.
AB  - : International service learning (ISL) courses within physical therapy (PT)
      education programs are designed, in part, to promote the development of
      professional values. Assessment of students' professional values, however, is a
      challenge for educators. METHODS: This study focused on the reflective learning
      component of an elective 10-day ISL course, evaluated whether PT professional
      values were manifested in students' written reflections, and characterized the
      level of student reflections using Bradley's criteria. Twenty-one third-year PT
      students participated. A qualitative content analysis of each student's written
      assignments was conducted. RESULTS: Although explicit instruction on PT values
      was not provided, reflections on professional values were identified in 97% of
      assignments. All three of Bradley's levels were found in all three written
      assignments, with the highest proportion of level 2 and 3 reflections being found
      in unstructured journals. CONCLUSION: Although no instruction specific to PT
      professional values was provided, values were implicit in student written
      assignments during this ISL course.

PMID- 30194825
TI  - Validation of an Instrument for Measuring Professional Behaviors Across Students
      Enrolled in Allied Health Professional Programs.
AB  - Students enrolled in professional education programs preparing for a career in a
      healthcare need to learn knowledge, skills, and a wide range of professional
      attributes. However, the nature of clinical and didactic curricula germane to
      allied health professional programs makes it difficult to find accurate and
      useful means of measuring knowledge of and the skills associated with
      professional behaviors. As allied health educators, it is critically important to
      identify a reliable and effective instrument that can assess professional
      attributes of students in terms of their knowledge and skill. In the current
      study, 180 of 189 students (response rate 95.2%) from five allied health
      pro!grams completed the online Professionalism Assessment Tool (PAT) to assess
      their professional attributes. The PAT was analyzed by each domain for internal
      consistency and by each item for floor and ceiling effects. Each domain met the a
      priori Cronbach alpha (range 0.90-0.94) and item floor effects were acceptable
      (range 1.17%-18.75%). Fourteen items in three domains exceeded a priori ceiling
      effects. Based upon the results of the current study, the PAT, originally created
      and validated for pharmacy students, appears to address common weaknesses
      identified in other instruments measuring professional behaviors within other
      health professional students.

PMID- 30194826
TI  - An Online Intervention Increases Empathy, Resilience, and Work Engagement Among
      Physical Therapy Students.
AB  - Health professions students often experience burnout and loss of empathy that
      worsens as they progress through their education. This study explored the impact
      of an evidence-based online course on physical therapy student empathy,
      resilience, and work engagement during their clinical internships. Participants
      included 36 doctoral physical therapy students who were beginning a sequence of
      three consecutive internships following their didactic coursework. Participants
      were randomly assigned to an immediate or delayed intervention group and received
      the online course during the first or second of the three internships. Outcome
      measures included the Jefferson Scale of Empathy, Utrecht Work Engagement scale,
      and GRIT resilience scale. The immediate intervention group made significant
      improvements in all three measures between the first and second internships
      compared to the delayed intervention group. These improvements were maintained
      over the 10-week duration of the second internship. The delayed intervention
      group made no significant changes in the three measures during the first
      internship; however, these each improved significantly at the end of the second
      internship. The study results suggest that online training can positively enhance
      physical therapy student empathy, resilience, and work engagement.

PMID- 30194827
TI  - Evaluating Clinical Performance of Student Physical Therapists: A Comparison of
      Student- and Staff-Managed Patient Outcomes After Hip Arthroplasty.
AB  - OBJECTIVE: To compare patient outcomes following acute rehabilitation after total
      hip arthroplasty (THA) of two groups: patients treated by student physical
      therapists (SPTs) under licensed physical therapist (PT) supervision and by
      licensed PTs. PARTICIPANTS: Seventy-eight patients with rehabilitation managed by
      supervised SPTs and 78 treated by licensed PTs. Inclusion criteria were admission
      between 2010 and 2014, first-time THA, age 55 to 70 yrs, and research consent.
      METHODS: Retrospective cohort review of electronic health records was conducted.
      The primary outcome measure was Activity Measure for Post-Acute Care (AM-PAC) 6
      Clicks Basic Mobility Short Form. OUTCOMES: Patient base!line and discharge
      outcomes measured by AM-PAC 6 Clicks were analyzed with mixed-model analysis of
      covariance. RESULTS: No significant difference was found in AM-PAC score between
      patient groups, even after differences in body mass index and session number were
      controlled. AM-PAC mean (SD) scores of SPT-managed cases changed from 14.5 (2.4)
      at baseline to 18.2 (2.1) at discharge; of PT-managed cases, from 14.4 (2.4) to
      18.2 (2.1). Outcomes were realized in fewer SPT-managed sessions than PT-managed
      sessions; distance ambulated was significantly greater in the PT-managed group.
      Discharge locations did not differ. CONCLUSION: AM-PAC scores after THA were
      equal whether patients were treated by supervised SPTs or licensed PTs.

PMID- 30194828
TI  - Use of an Academic Professional Behavior Assessment and Intervention to Promote
      Professional Socialization.
AB  - BACKGROUND: Professional socialization is the period in which a professional
      acquires the specialized skills, knowledge, and attitude of the profession.
      Professional socialization of physical therapy students begins day one in the
      classroom and continues through the transition to the clinic. To promote
      professional socialization among Doctor of Physical Therapy (DPT) students, an
      Academic Professional Behavior Assessment (APBA) and advising plan were developed
      to identify, quantify, and improve professional behaviors. AIMS: This study
      explored the ability of the APBA to identify student professional behavior
      concerns and to determine the effectiveness of the advising plan to prepare the
      DPT student for transition to the clinic. METHODS: In this quasi-experimental
      study, DPT students (n=244) at a single university from 2004-2011 were assessed
      on the APBA every semester in all didactic courses. If behavior concerns were
      identified in two or more courses, students regularly met with their advisors for
      advising and to develop a professional behavior plan for improvement. RESULTS:
      The evaluation process flagged 17% (n=42) of the students for advising. Of those
      who received advising, 36% (n=15) went on to have concerns in the clinical phase
      of their education. A student who met the APBA criteria was 97% more likely to
      pass the clinical phase of the program. Students were most often flagged for
      problems with professionalism and interpersonal communication regardless of
      timeframe and instruction style. CONCLUSIONS: This study suggests that early
      professional socialization during the classroom portion of a student's DPT
      education is effective in shaping substandard professional behaviors and
      positively impacting later clinical performance.

PMID- 30194829
TI  - Neuropathy and Other Risk Factors for Lower Extremity Amputation in People with
      Diabetes Using a Clinical Data Repository System.
AB  - AIMS: The purpose of the study was to identify the frequency of a prior diagnosis
      of neuropathy, peripheral vascular disease (PVD), and foot ulceration in patients
      with diabetes who subsequently underwent lower extremity amputation (LEA).
      METHODS: We performed a retrospective electronic review of de-identified charts
      from a tertiary medical health center of patients who had the diagnosis codes of
      diabetes and the procedure codes of LEA. For this query, neuropathy, PVD, and
      foot ulcer diagnosis codes were selected as the variables of interest. The
      timeline of events was defined as the first-ever diagnosis of diabetes, followed
      by the first-ever diagnosis of any of the risk factors, followed by the first
      ever procedure of LEA. The frequency of each risk factor was counted individually
      and the different combinations of risk factors were calculated. RESULTS: The
      search yielded 844 patients who had a diabetes diagnosis prior to LEA. We found
      that 669 (79.3%) of the patients had one or more of the risk factors before LEA.
      From the 844 patients, 414 (49.1%) had neuropathy, 402 (47.6%) had a foot ulcer,
      and 495 (58%) had a PVD diagnosis. Investigating the frequency of patients who
      have multiple risk factors, we found that 28.9% had two risk factors and 23.6%
      had three risk factors. CONCLUSIONS: The majority of LEA procedures were done for
      patients with at least one diabetic LEA risk factor. Our findings provide recent
      quantitative support of known risk factors' association with amputation, and the
      presence of risk factors war!rants escalation in prevention strategies.

PMID- 30194830
TI  - Career Satisfaction in the Profession of Medical Laboratory Science.
AB  - The purpose of this research was to determine which job features create
      motivation and career satisfaction to retain personnel in the medical laboratory
      profession. Four research questions based on Wlodkowski's theory of motivation
      guided the study: Is there a difference in perceived career satisfaction among
      medical laboratory scientists who: a) feel included by practitioners in other
      healthcare professions, b) have choices on the job that are personally relevant,
      c) feel more challenged, and d) feel more competent in their daily work? In order
      to answer these questions, a survey composed of 33 questions was developed to
      capture the opinions of medical laboratory professionals who worked in the United
      States and had at least 1 year of experience. The survey was deployed online and
      posted on social media sites. Results, based on responses from 333 participants,
      showed that medical laboratory personnel are more satisfied with their career
      when they feel included with other healthcare professionals, make choices that
      are personally relevant, and feel challenged in their work. If current
      professionals are more satisfied in their work, they might remain in the
      workforce, and new professionals might be attracted to join the profession,
      helping to alleviate the shortage of medical laboratory scientists.

PMID- 30194831
TI  - Virtually Certified: Development of an Online Oral Examination Phase for a
      National Advanced Practice Certification Model for Radiation Therapists in
      Canada.
AB  - Following development of a framework to establish the scope of advanced practice
      for radiation therapists (APRTs), a Canadian certification process was built.
      This involved three independently-assessed phases: professional portfolio, case
      submission, and oral examination. The oral examination was to test the
      candidate's knowledge and capacity for decision-making. Development and piloting
      involved 3 elements: 1) content development, including relevant case selection,
      with accompanying high-fidelity imaging and resources; 2) harnessing of
      technology and ensuing logistics, given the desire to offer the examination
      online, maximizing accessibility and minimizing resources; and 3) examiner
      recruitment and preparation, involving a national call for interprofessional
      examiners, to assess across the spectrum of competencies. Each element was
      approached systematically, with modifications made iteratively. Three overarching
      challenges required ongoing attention and consideration: resource-intensiveness
      of building and validating cases, ensuring applicability and relevance of case
      content and "answers" across practice environments, and preparation of non
      radiation therapist (oncologist and physicist) examiners regarding APRT
      standards. The resultant examination model is thought to be a robust assessment
      tool, well-regarded by candidates and examiners as fair and transparent, and
      complementary to the other certification phases. A consultatory pilot process
      supported establishment of a robust framework that is believed to be defensible
      and preliminarily valid.

PMID- 30194832
TI  - A Curriculum for an Interprofessional Seminar on Integrated Primary Care:
      Developing Competencies for Interprofessional Collaborative Practice.
AB  - Health care is increasingly delivered through team-based, collaborative
      strategies with interprofessional education as an important mechanism for
      building interprofessional practice competencies. This paper describes an
      Interprofessional Seminar on Integrated Primary Care (IS-IPC) designed to meet
      this educational need with interprofessional team-based learning as the
      foundation of an iterative process such that education and practice inform one
      another. The IS-IPC can be used to educate an interprofessional group of learners
      about key topics relevant to working together in integrated primary care. The IS
      IPC describes steps in developing an interprofessional seminar, common
      challenges, and their solutions in creating interprofessional learning
      experiences, and eight foundational content modules containing an outline and
      curricular resources. The IS-IPC facilitates interprofessional educator
      partnerships at the local level and can be customized to fit the local
      environment, pedagogical philosophy, and learning objectives.

PMID- 30194833
TI  - Collaborations in Clinical Education: Coordinating Top-Down and Bottom-Up Efforts
      to Advance Best Practices in Physical Therapist Education.
AB  - BACKGROUND: Preparing students for today's healthcare environment requires
      visionary leadership and strategic implementation at the grassroots level. This
      paper describes the process used in physical therapy (PT) to gather information
      about regional clinical education consortia, enhance networking, and improve
      connectivity with national initiatives. PROCESS: Twenty consortia shared
      information about their structures, processes, and outcomes during small-group
      discussions using a mixed methods approach. Two additional consortia were later
      identified and interviewed. FINDINGS: Consortia structure varied, but an average
      lifespan of 27 yrs with limited turnover was noted. Most consortia included both
      academic/clinical educators and PT/PTA educators. Commonly reported processes
      included holding meetings, serving as peer network, mentoring new members, and
      collaborating on research. The most frequent outcome was education of
      stakeholders. Consortia supported national initiatives but voiced need for more
      engagement at the grassroots level. DISCUSSION: Regional consortia play a vital
      role in shaping the future of clinical education but increased coordination
      between top-down and bottom-up efforts is needed. Recommendations were developed
      to use technologies, develop systematic communications, facilitate regional and
      national networks, and promote inclusion of all stakeholders. CONCLUSION: A
      systematic process engaging grassroots organizations can prove valuable for
      coordinating top-down and bottom-up efforts in all health professions.

PMID- 30194834
TI  - Development and Preliminary Assessment of Interprofessional Education Focused on
      Vulnerable Populations.
AB  - With the current state of the U.S. healthcare system, interprofessional
      collaborative practice (IPCP) has never been more important. Health professions
      educators are increasingly incorporating interprofessional education (IPE) in
      their curricula in order to prepare students for IPCP. The Health- Focused IPE
      Community of Practice (representing nursing, occupational therapy, pharmacy,
      physical therapy, rehabilitation counseling, social work, and speech-language
      pathology) at the University of Texas at El Paso has created a unique IPE model
      centered on vulnerable populations. The purposes of this paper are to describe
      the early development of this innovative IPE model and present findings from an
      evaluation of an IPE learning experience focused on a case involving a
      transgender individual. The evaluation of the first IPE activity demonstrated
      that the students' knowledge and attitudes related to interprofessional
      collaboration improved for all participating professions. Additionally, the post
      training evaluation revealed that students were more comfortable providing
      services to transgender individuals than interacting with them. This IPE model
      has leveraged the strengths of community-engaged faculty in order to infuse
      content related to vulnerable populations across multiple curricula. This
      holistic approach models to the students that complex problems require
      multifaceted solutions generated by IPCP.

PMID- 30194835
TI  - In-TICE: An Integrated Tool for Interprofessional Clinical Educators.
AB  - Clinical educators in healthcare disciplines/professions are expected to
      synthesize research-based models and strategies into their own unique supervisory
      style. Therefore, best practice is to provide systematic cross-disciplinary
      training tools that assist clinical educators in meeting this expectation. The
      authors--from the disciplines of nursing, speech-language pathology, physical
      therapy, and occupational therapy--examined learning theories, models of
      supervision, and strategies for clinical education and determined common themes
      across and within them. This led to the creation of a summative and integrated
      tool (the Integrated Tool for Interprofessional Clinical Educators, In-TICE) to
      assist clinical educators in linking conceptual models/theories and supervisory
      strategies and applying them in their practice. The tool, coined In-TICE, was
      then used as a guide for problem solving case study examples during an
      interprofessional workshop. In-TICE may offer a significant contribution to the
      systematic training of clinical educators across healthcare professions, as it
      can be applied across all practice settings.

PMID- 30194836
TI  - Role of Community and Professional Engagement in Allied Health Higher Education:
      The Academic Perspective.
AB  - Community and professional engagement describes a collaborative model of
      interaction between institutions of higher education and the communities in which
      they operate. This qualitative study aimed to examine how professional and
      community engagement is understood and incorporated into the role of staff
      members within the School of Health Sciences of one university. Twenty-one
      academic and professional staff were interviewed. Participants identified a range
      of definitions for both 'community' and 'professional' engagement, as well as the
      benefits and limitations of such engagement. Ability to conduct engagement was
      limited by time capacity when competing with other role requirements. Integration
      of community engagement with research and teaching requires development of a
      framework that addresses both the common barriers and facilitators to engagement.

PMID- 30194837
TI  - Students' Knowledge and Self-Perceptions Regarding Integrative Medicine and
      Health Following Training in First-Year Graduate PA, PT, and OT Programs.
AB  - Integrative medicine and health (IMH) content and pedagogy for health
      professional education best practices are not established. Physician assistant
      (PA), physical therapy (PT), and occupational therapy (OT) students' knowledge
      and self-perception of integrative health, lifestyle behavior change, and
      professional well-being were assessed pre- and post- participation in IMH online
      modules. Students demonstrated significant increases in knowledge and self
      perception scores from pre- to post-test. Pre- and post-test knowledge score
      means varied by discipline. Pre-test self-perception score means did not vary
      across disciplines, while the post-test self-perception score mean was
      significantly higher for PA students compared to other disciplines. Online
      integration of IMH content does not require significant curricular revisions and
      is a promising pedagogy for increasing PA, PT, and OT students' understanding of
      the IMH approach.

PMID- 30194838
TI  - Recognition of modified cytosine variants by the DNA-binding domain of methyl
      directed endonuclease McrBC.
AB  - Cytosine modifications expand the information content of genomic DNA in both
      eukaryotes and prokaryotes, providing means for epigenetic regulation and self
      versus nonself discrimination. For example, the methyl-directed restriction
      endonuclease, McrBC, recognizes and cuts invading bacteriophage DNA containing 5
      methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC), and N4-methylcytosine
      (4mC), leaving the unmodified host DNA intact. Here, we present cocrystal
      structures of McrB-N bound to DNA oligoduplexes containing 5hmC, 5-formylcytosine
      (5fC), and 4mC, and characterize the relative affinity of McrB-N to various
      cytosine variants. We find that McrB-N flips out modified bases into a protein
      pocket and binds cytosine derivatives in the order of descending affinity: 4mC >
      5mC > 5hmC ? 5fC. We also show that pocket mutations alter the relative
      preference of McrB-N to 5mC, 5hmC, and 4mC.

PMID- 30194839
TI  - Considering a Weight Criterion for Neonatal Tracheostomy: An Analysis of the ACS
      NSQIP-P.
AB  - OBJECTIVES: Neonates weighing < 2.5 kg have known higher rates of surgical
      mortality and morbidity, but this remains unexamined specifically for
      tracheostomy. We present outcomes of neonates undergoing tracheostomy stratified
      by weight. METHODS: Retrospective review of the American College of Surgeons
      National Surgical Quality Improvement Program-Pediatric from 2012 to 2014.
      Patients undergoing tracheostomy were included. Thirty-day mortality and
      major/minor complication rates were stratified by weight (group 1: < 2.5 kg;
      group 2: >= 2.5 kg and < 4 kg; group 3: >= 4 kg). Patient comorbidities were
      assessed for independent risk factors of morbidity and mortality. RESULTS: Of
      183,233 patients, 543 underwent tracheostomy. Forty-four patients were group 1
      (mean: 2.2 kg +/- 0.25); 170 patients were group 2 (mean: 3.31 kg +/- 0.42); and
      329 patients were group 3 (mean: 6.4 kg +/- 2.7). Between groups 1 and 2, there
      were no significant differences in mortality (P = 0.47), major complication rates
      (P = 0.99), or minor complication rates (P = 0.64). In comparing all three
      groups, there were no significant differences in mortality (P = 0.47), major
      complication rates (P = 0.80), or minor complication rates (P = 0.77). The
      overall 30-day mortality for all patients was 4.24%. In a multivariate logistical
      regression model, weight group did not change the odds of all negative outcomes
      (group 1: odds ratio [OR] of 0.71; 95% confidence interval [CI], 0.33-1.53 and
      group 2: OR of 0.78; 95% CI, 0.50-1.22). Bronchopulmonary dysplasia was the only
      independent significant predictor of major complications (OR, 1.69; 95% CI, 1.02
      2.79) (P = 0.04). CONCLUSION: Our data indicate that 30-day mortality and
      morbidity outcomes for neonatal tracheostomy are not affected by weight. Overall
      30-day mortality should be discussed with caregivers preoperatively. LEVEL OF
      EVIDENCE: 4. Laryngoscope, 2018.

PMID- 30194840
TI  - Lacrimal Sac Rhinosporidiosis and Surgical Management by Transnasal Endoscopic
      Excision: A Case Series.
AB  - OBJECTIVES: To study the clinical profile and the route of spread of lacrimal sac
      rhinosporidiosis. To device a standard transnasal endoscopic surgical procedure
      in the treatment of lacrimal sac rhinosporidiosis. METHODS: This is a
      retrospective analysis of a case series on lacrimal sac rhinosporidiosis.
      Thirteen cases of lacrimal sac rhinosporidiosis reported in our institution from
      July 2003 to July 2016 were included. Workup included diagnostic nasal endoscopy
      and lacrimal syringing. All patients underwent transnasal endoscopic excision of
      rhinosporidiosis. RESULTS: Lacrimal sac rhinosporidiosis was more prevalent among
      males and in the 31 to 40 years age group. All patients had a history of bathing
      in stagnant water bodies. The most common clinical presentation was a doughy
      swelling medial to the medial canthus. Lacrimal sac rhinosporidiosis invariably
      presented with involvement of the nasolacrimal duct. Following the endoscopic
      excision of lacrimal sac rhinosporidiosis, all patients were followed up for a
      mean period of 16 months, and only one patient had recurrence. CONCLUSION: A
      unique aspect of our case series is that patients presented with features
      pertaining to isolated lacrimal system involvement rather than sinonasal
      involvement. Involvement of the nasolacrimal duct and nasal cavity without
      involvement of the eyes in all cases confirms the retrograde spread of
      rhinosporidiosis from the nasal cavity into the lacrimal sac via the nasolacrimal
      duct as the most common route of spread of infection. We recommend that
      endoscopic dacryocystorhinostomy, along with nasolacrimal duct excision used for
      surgical management in our case series with superior results, must become the
      standard of care in treatment of this condition. LEVEL OF EVIDENCE: 4.
      Laryngoscope, 2018.

PMID- 30194841
TI  - Production of lactobionic acid from lactose using the cellobiose dehydrogenase-3
      HAA-laccase system from Pycnoporus sp. SYBC-L10.
AB  - The aim of this study was to produce lactobionic acid from lactose by a new
      Pycnoporus sp. SYBC-L10 strain. Recently, studies on enzymatic production of
      lactobionic acid mostly focus on cellobiose dehydrogenase from Sclerotium rolfsii
      CBS 191.62 and laccase from Trametes pubescens MB 89 oxidize lactose to
      lactobionic acid with redox mediators. In this study, we converted lactose to
      lactobionic acid by shaking flask fermentation without exogenous mediator in the
      reaction mixture. In this bioconversion process, lactose is efficiently converted
      into lactobionic acid with a specific productivity of up to 3.1 g l-1  h-1 and
      96% yield. 3-Hydroxyanthranilic acid added externally to the reaction mixture can
      obviously accelerate the conversion of lactose to lactobionic acid. The results
      showed that 3-hydroxyanthranilic acid produced by the fungus itself is an
      important influencing factor in this bioconversion process. This study presents
      the first attempt to efficiently produce lactobionic acid by white-rot fungi,
      suggesting definite potential for Pycnoporus to produce lactobionic acid.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Lactobionic acid has been applied to a wide
      range of applications in pharmaceutical, food, nanotechnology and chemical
      industries. Here, an attempt was done to produce lactobionic acid from lactose
      using the cellobiose dehydrogenase-3-HAA-laccase system in a fermentation system.
      After a survey of other methods to produce lactobionic acid by cellobiose
      dehydrogenase, this study explores a new and significant perspective for the
      production of lactobionic acid.

PMID- 30194842
TI  - Combination of panendoscopy and positron emission tomography/computed tomography
      increases detection of unknown primary head and neck carcinoma.
AB  - OBJECTIVES/HYPOTHESIS: With positron emission tomography/computed tomography
      (PET/CT) now commonplace as a diagnostic tool, new questions have arisen
      regarding the utility and cost-effectiveness of panendoscopy. In this
      retrospective review of a large cohort of head and neck squamous cell carcinoma
      of unknown primary (HNSCC-UP), we describe the enduring utility of panendoscopy
      in the detection of the primary site of mucosal disease even when PET/CT is
      negative. STUDY DESIGN: Retrospective cohort study. METHODS: A retrospective
      analysis of patients presenting to the senior author (y.d.) from July 1 1997 to
      July 1 2017 with fine-needle aspiration-proven metastatic squamous cell carcinoma
      to the neck. All patients underwent formal panendoscopy (direct laryngoscopy,
      bronchoscopy, and rigid esophagoscopy). Presence of squamous cell carcinoma on
      final pathology was examined. RESULTS: A total of 190 patients had HNSCC-UP, with
      87 positive and 103 negative on PET/CT. Of the PET/CT-negative patients, 71
      patients retained the HNSCC-UP designation after panendoscopy. Eighteen patients
      (56% of cases) were found to have primary tonsillar squamous cell carcinoma.
      Eight of 32 primary sites were found in the base of tongue (25%), with HPV
      positivity in two of these patients. The sensitivity and negative predictive
      value of PET/CT in detecting the primary site in unknown primary head and neck
      squamous cell carcinoma in the total study population were 73.1% and 68.9%,
      respectively. CONCLUSIONS: Surgical panendoscopy has an important role in the
      workup of patients with unknown primary head and neck squamous cell carcinoma.
      There is a high rate of cancer diagnosis, even in PET/CT negative patients. LEVEL
      OF EVIDENCE: 4 Laryngoscope, 2573-2575, 2018.

PMID- 30194843
TI  - Safety and efficacy of uninterrupted versus minimally interrupted periprocedural
      DOACs for implantation of cardiac devices in patients with AF.

PMID- 30194844
TI  - Inflammatory myopathies after allogeneic stem cell transplantation.
AB  - : Introduction,: Graft-versus-host disease (GVHD) is a recognized complication of
      allogeneic stem cell transplantation (allo-SCT) and may affect muscle. We
      investigated the incidence and subtypes of inflammatory myopathy (IM) in South
      Australian recipients of allo-SCT. METHODS: Recipients of allo-SCT from 2004 to
      2014 at the Royal Adelaide Hospital were identified. Records were reviewed to
      identify patients with weakness, creatine kinase (CK) elevation, and muscle
      biopsy confirming IM. RESULTS: Weakness was present in 32 of 224 patients who
      received allo-SCT patients reviewed, and CK was raised in 7 of 20 patients with
      weakness. Six patients developed biopsy-confirmed IM; 3 patients had chronic GVHD
      related myopathy, 2 had necrotizing myopathy, and 1 had dermatomyositis (DM)
      associated with anti-melanoma differentiation associated protein 5 (MDA5)
      antibodies. The incidence of IM was calculated to be 2 cases per thousand
      annually. DISCUSSION: Among recipients of allo-SCT, weakness is common, and the
      incidence of IM is increased. Histopathological diagnoses are varied, and we
      report findings of necrotizing myopathy and anti-MDA5-associated DM. Muscle
      Nerve, 2018.

PMID- 30194845
TI  - Oropharyngeal Injury From Spontaneous Combustion of a Lithium-ion Battery: A Case
      Report.
AB  - Lithium-ion batteries have been used for more than 20 years, most recently to
      power handheld devices including cellphones and electronic nicotine-delivery
      systems. They have garnered significant media attention due to thermal-related
      injuries occurring after spontaneous combustion. Spontaneous combustion of a
      lithium-ion battery occurs due to a process that is referred to as the thermal
      runaway effect. Here, we review the case of a 25-year-old female with severe
      oropharyngeal and upper aerodigestive thermal injuries after spontaneous
      combustion of a lithium-ion battery in a flashlight. We discuss the associated
      management and provide a review of the literature detailing similar injuries.
      Laryngoscope, 2018.

PMID- 30194846
TI  - When Should Parotidectomy and a Neck Dissection Be Performed in Cutaneous SCC of
      the Head and Neck?

PMID- 30194847
TI  - Why pulse oximetry is inaccurate in liver cirrhosis - ancient knowledge.
AB  - With great interest we read the manuscript by Forde et al., regarding pulse
      oximetry as a screening tool for hepatopulmonary syndrome (HPS) (1). Their
      results indicate that pulse oximetry is insensitive for HPS detection in patients
      with liver cirrhosis. We aimed to further clarify the underlying physiologic
      mechanisms that result in poor correlation between pulse oximetry and arterial
      oxygenation in this patient population. This article is protected by copyright.
      All rights reserved.

PMID- 30194848
TI  - To kiss or not to kiss in the era of the human papillomavirus-associated head and
      neck cancer "epidemic"?

PMID- 30194849
TI  - Impact of hydration status on haemodynamics, effects of acute blood pressure
      lowering treatment, and prognosis after stroke.
AB  - AIMS: Although high blood pressure (BP) is common in acute stroke and associated
      with poor outcome, the Efficacy of Nitric Oxide in Stroke (ENOS) trial showed no
      beneficial effect of antihypertensive treatment in this situation.
      Antihypertensive agents have accentuated effects in dehydrated patients. We
      assessed the impact of dehydration on haemodynamics, the effects of
      antihypertensive treatment, and prognosis in the ENOS trial. METHODS: ENOS
      randomized 4011 patients with acute stroke and raised systolic BP to a glyceryl
      trinitrate (GTN) patch or no GTN patch, and to continue or to stop existing
      antihypertensive treatment within 48 h of onset. The primary outcome was
      functional outcome (modified Rankin Scale, mRS) at day 90. Blood markers of
      dehydration at baseline were collected at two sites (n = 310) and their
      relationship with haemodynamics and outcome was assessed. RESULTS: There were no
      significant associations between dehydration markers and fall in blood pressure
      from baseline to day 1, and no significant interaction with allocated treatment.
      Overall, increasing urea was associated with an unfavourable shift in mRS [odds
      ratio 3.43, 95% confidence interval (CI) 1.42, 8.32; P = 0.006] and increased
      risk of death at day 90 (hazard ratio 4.55, 95% CI 1.51, 13.66; P = 0.007).
      CONCLUSIONS: Blood pressure-lowering treatment was safe in dehydrated patients,
      with no precipitous changes in BP, thus supporting its use in acute stroke prior
      to blood markers of dehydration becoming available. Increased baseline urea was
      associated with poor prognosis after stroke.

PMID- 30194850
TI  - Fertility induction in hypogonadotropic hypogonadal men.
AB  - Men with hypogonadotropic hypogonadism (HH) are typically azoospermic, and yet HH
      is one of the few treatable forms of male infertility. Sperm induction protocols
      using gonadotrophins aim to replicate the natural endocrine control of
      spermatogenesis. Previously virilised men with adult-onset HH and normal
      testicular volume respond well to monotherapy in which human chorionic
      gonadotrophin (hCG) acts as a long-acting LH-analogue stimulating
      spermatogenesis. However, this approach is rarely successful for men with
      congenital HH (CHH) (eg, Kallmann syndrome), for whom combined gonadotrophin
      therapy (hCG + follicle-stimulating hormone [FSH]) is an absolute requirement to
      maximise fertility potential. Key baseline predictors of successful
      spermatogenesis-induction include prior spontaneous testicular development (ie,
      testicular volume [TV] > 4 mL), serum inhibin B (IB ) concentration >60 pg/mL and
      no history of maldescended testes (cryptorchidism).

PMID- 30194851
TI  - Structure of Asp-bound peptidase E from Salmonella enterica: Active site at dimer
      interface illuminates Asp recognition.
AB  - Peptidase-E, a nonclassical serine peptidase, is specific for dipeptides with an
      N-terminal aspartate. This stringent substrate specificity remains largely
      unexplained. We report an aspartate-bound structure of peptidase-E at 1.83 A
      resolution. In contrast to previous reports, the enzyme forms a dimer, and the
      active site is located at the dimer interface, well shielded from the solvent.
      Our findings further suggest that the stringent aspartate specificity of the
      enzyme is due to electrostatics and molecular complementarity in the active site.
      The new structural information presented herein may provide insights into the
      role of functionally important residues in peptidase-E.

PMID- 30194853
TI  - Effects of electrode size and surface morphology on electrode polarization in
      physiological buffers.
AB  - Electrode polarization (EP) is inevitable in high conductivity buffers at low AC
      frequencies due to the accumulation of free charges at the electrode/electrolyte
      interface. Electrode miniaturization increases EP effect on impedance
      measurements. In this paper, six gold planar (GP) electrodes having different
      diameters ( 100MUm<=phi<=4000MUm ) were used to investigate the size effect on EP
      with parallel plate electrode geometry. GP electrode surface was
      electrochemically deposited with gold nanostructures (GNs) to minimize the EP
      effect. Equivalent circuit model was used to attain electrode/electrolyte
      interfacial impedance. Constant phase element model was used to analyze the
      relation between the size and morphology of electrodes on EP. The surface
      morphology of gold nanostructured electrodes was examined using SEM, and the
      influence of different applied potential on the growth of GNs was elucidated with
      Nernst equilibrium condition. Surface roughness and wettability characteristics
      were examined performing surface roughness and contact angle measurements,
      respectively. The improvement of GNs deposited electrode performance was
      investigated by analytically generated Jurkat cell suspension spectra. The
      results show that the error in estimating the subcellular properties can be
      drastically reduced by using GNs deposited electrodes.

PMID- 30194852
TI  - Submicroscopic Plasmodium infection during pregnancy is associated with reduced
      antibody levels to tetanus toxoid.
AB  - Submicroscopic Plasmodium infections in pregnancy are common in endemic areas,
      and it is important to understand the impact of these low-level infections.
      Asymptomatic, chronic infections are advantageous for parasite persistence,
      particularly in areas where the optimal eco-epidemiological conditions for
      parasite transmission fluctuate. In chronic infections, the persistence of the
      antigenic stimulus changes the expression of immune mediators and promotes
      constant immune regulation, including increases in regulatory T cell populations.
      These alterations of the immune system could compromise the response to routine
      vaccination. This study aimed to evaluate the effect of submicroscopic plasmodial
      infection with P. falciparum and P. vivax during pregnancy on the immune response
      to the tetanus toxoid vaccine in Colombian women. Expression of different
      cytokines and mediators of immune regulation and levels of anti-tetanus toxoid
      (TT) immunoglobulin (Ig)G were quantified in pregnant women with and without
      submicroscopic plasmodial infection. The anti-TT IgG levels were significantly
      lower in the infected group compared with the uninfected group. The expression of
      interferon (IFN)-gamma, tumour necrosis factor (TNF) and forkhead box protein 3
      (FoxP3) was significantly higher in the infected group, while the expression of
      cytotoxic T lymphocyte antigen 4 (CTLA-4) and transforming growth factor (TGF)
      beta was lower in the group of infected. In conclusion, submicroscopic Plasmodium
      infection altered the development of the immune response to the TT vaccine in
      Colombian pregnant women. The impact of Plasmodium infections on the immune
      regulatory pathways warrants further exploration.

PMID- 30194854
TI  - Covalent organic framework TpPa-1 as stationary phase for capillary
      electrochromatographic separation of drugs and food additives.
AB  - Because of unique properties like permanent porosity, low density and large
      surface area, covalent organic frameworks are attractive microporous materials as
      stationary phase for CEC. Among them, COF-TpPa-1 possesses extraordinary chemical
      stability and common features of covalent organic frameworks. So, COF-TpPa-1
      could be a promising material as stationary phase to enhance separation
      selectivity and tolerate the acid or alkaline electrochromatographic separation
      conditions. Here, we report the preparation of COF-TpPa-1 modified capillary
      column by in situ growth for electrochromatographic separation. The
      immobilization of COF-TpPa-1 on the inner wall of capillary column was confirmed
      by Fourier transform infrared spectroscopy, scanning electron microscopy and X
      ray diffraction. The fabricated COF-TpPa-1 modified capillary column indicated
      good resolution for the separation of neutral analytes, nonsteroidal anti
      inflammatory drugs and food additives in open-tubular CEC mode. Compared with
      bare capillary column, the COF-TpPa-1 modified capillary column improved
      separation selectivity remarkably for tested analytes, including hydrophobic, pi
      pi and hydrogen bond interactions. Besides, the prepared capillary column showed
      excellent repeatability and stability. The intraday, interday and column-to
      column relative standard deviations of migration time for neutral analytes were
      less than 3.54%. This work shows enamine-linked covalent organic frameworks have
      great potential as stationary phases in CEC.

PMID- 30194855
TI  - Reproducibility of motor unit number index and multiple point stimulation motor
      unit number estimation in controls.
AB  - INTRODUCTION: Reproducibility of the multiple point stimulation motor unit number
      estimation (MPS-MUNE) technique was compared with the recently developed motor
      unit number index (MUNIX) technique. METHODS: MPS-MUNE and MUNIX were performed
      on 15 healthy subjects at 3 different time-points by the same examiner.
      Reproducibility was analyzed using intraclass correlation coefficient (ICC) and
      coefficient of variation (CV). RESULTS: ICC values for MUNIX and MPS-MUNE were
      excellent across 3 tests (0.80 and 0.77, respectively), although CV values were
      significantly lower for MUNIX than MPS-MUNE (P < 0.01). In addition, test-retest
      reproducibility was better for MUNIX, a finding largely attributable to poor
      reproducibility of the single motor unit action potential area. MUNIX (R = -0.48,
      P < 0.05) and MPS-MUNE (R = -0.53, P < 0.05) were significantly correlated with
      age. DISCUSSION: MUNIX demonstrated better intrarater reproducibility and may be
      a more reliable neurophysiological biomarker than MPS-MUNE. Muscle Nerve 58: 660
      664, 2018.

PMID- 30194856
TI  - Antiepileptic drugs are associated with central hypothyroidism.
AB  - OBJECTIVE: Studies in children have shown an increased frequency of central
      hypothyroidism (CH) with long-term use of antiepileptic drugs (AEDs). The aim of
      this study was to search for CH in adults treated with AEDs and find whether the
      type of AEDs used matters. MATERIALS AND METHODS: Adult epileptic patients
      treated at the neurology outpatient clinic at Landspitali University Hospital
      (LSH) from 1998 to 2011 were included. Patients were invited for a blood test if
      serum levels for TSH (s-TSH) or free-T4 (s-fT4 ) had not already been obtained.
      CH was defined as s-fT4 below the reference range (12-22 pmol/L) and normal s-TSH
      levels (0.30-4.20 mIU/L). Data were analyzed using logistic regression and Mann
      Whitney test. RESULTS: We identified 165 patients (92 women), mean age 45.6 (+/
      15.5, range: 20-92) years. The mean s-fT4 -level in our group was 14.2 (+/-2.9,
      range: 8.1-24.4) pmol/L compared with 16.9 (+/-6.1) pmol/L in a sample of 13248
      measurements at LSH during one year (LSH-group) (P < 0.001). The difference in s
      fT4 -level between men and the LSH-group was significant and also for women (P <
      0.001 and P < 0.001, respectively). Thirty-five patients (21%) had CH. A
      significant association with the use of carbamazepine or oxcarbazepine was found,
      odds ratio for women 15.0 (95% CI: 4.6-49.5) and 1.8 (95% CI: 0.4-8.3) for men.
      CONCLUSION: 21% of patients treated with AEDs had CH, more often patients taking
      carbamazepine or oxacarbazepine, and more often women. The s-fT4 -level was lower
      among patients treated with AEDs.

PMID- 30194858
TI  - Development and evaluation of rhinoplasty spreader graft suture simulator for
      novice surgeons.
AB  - OBJECTIVE: Surgical simulators aimed at mimicking elements of rhinoplasty
      surgery, specifically those aimed at improving cartilage suturing, are not
      available. Here, we present a surgical simulator for spreader graft placement
      that uses cartilage rather than synthetic materials and gauge improvement using
      objective measures for suture placement accuracy, speed, and efficiency of hand
      motion. METHODS: Twenty-two otolaryngologists in two groups (residents [10] and
      experts [12]) were instructed to secure the two spreader graft specimen into
      position with three mattress sutures on a nose model that used porcine septal
      cartilage as a proxy for the human counterpart. Hand motion was tracked using an
      electromagnetic position sensing device. The time required to complete the suture
      task, total hand displacement, cumulative number of hand motion direction
      changes, and accuracy of suture insertion were measured. These measurements were
      compared between the two cohort groups for construct validity. The subjects
      completed a survey to evaluate realism and value of the model. RESULTS: The
      expert group had a lower mean time required to complete the task (P < 0.05),
      total hand displacement (P < 0.01), and number of hand motion direction changes
      (P < 0.001). No significant difference was observed between the two groups in
      suture precision measurement. The subjects agreed on the face validity and
      usefulness of the trainer. CONCLUSIONS: Our study suggests that the simulator may
      be a useful tool to objectively gauge suturing efficiency. Devices such as this
      may be useful for developing skill with suturing cartilage tissue and potentially
      be used to assess resident acquisition of surgical skill. LEVEL OF EVIDENCE: NA.
      Laryngoscope, 2018.

PMID- 30194857
TI  - The effect of aging on drug-induced sleep endoscopy findings.
AB  - OBJECTIVES/HYPOTHESIS: To evaluate the correlation of aging and upper airway
      collapse characteristics observed by drug-induced sleep endoscopy (DISE), and
      report the observed differences on obstructive sleep apnea (OSA) subjects, older
      and younger than 60 years. STUDY DESIGN: Case series. METHODS: This study
      analyzed the data of 200 OSA patients who underwent DISE between January 1, 2013
      and June 30, 2017. The variables sex, body mass index (BMI), Epworth Sleepiness
      Scale score, tonsil size, modified Mallampati (MM) classification, apnea-hypopnea
      index (AHI), oxygen desaturation index (ODI), lowest oxygen saturation, and VOTE
      (velum, oropharynx, tongue base, epiglottis) classification were compared between
      two groups: <60 and >=60 years old. RESULTS: Older age had significant
      correlation with higher AHI, ODI, lower O2 nadir, multisite obstruction, combined
      upper (palatopharyngeal) + lower (hypopharyngeal) level obstructions, and
      complete anterior-posterior (AP) velum collapse pattern. Lateral oropharyngeal
      wall collapse was significantly lower in the older group. Findings remained
      statistically significant when adjusted for sex, BMI, tonsil size, and MM.
      CONCLUSIONS: Aging was an independent factor that directly correlated with
      increased AHI and hypoxemia, multisites, combined levels of obstruction, and
      complete AP velum collapse pattern. Being older than 60 years had higher of
      complete AP velum collapse and lower incidence of lateral oropharyngeal wall
      collapse, regardless of OSA severity and tonsil size. LEVEL OF EVIDENCE: 4
      Laryngoscope, 2644-2650, 2018.

PMID- 30194859
TI  - Biofluid pumping and mixing by an AC electrothermal micropump embedded with a
      spiral microelectrode pair in a cylindrical microchannel.
AB  - In this paper, we numerically investigated a multifunctional AC electrothermal
      (ACET) micropump embedded with an asymmetric spiral microelectrode pair in a
      cylindrical microchannel for simultaneous pumping and mixing in high-conductivity
      fluids, which makes the pump useful for biofluid applications. When an AC signal
      was applied to the asymmetric spiral electrode pair, the vortices induced on the
      electrode surfaces with centerlines along the corresponding spiral electrode
      length exhibit a spiral distribution, and the net flow in the cylindrical
      microchannel is generated by the ACET effect. The vorticity field distribution
      can explain the mechanism of simultaneous pumping and mixing. Because the
      vorticity field is inclined against the microchannel direction, vortices on top
      of the spiral electrodes can affect the ACET flow in the following two aspects at
      the same time: one is pumping the flow in the microchannel direction, and the
      other is mixing the samples by stirring the flow. We also determined that the
      geometric ratios of the electrode width to the gap or slant angle of the spiral
      electrodes can feasibly be used to control the relative strength of the pumping
      and mixing capabilities, and we achieved an optimal design that gives both
      desirable pumping and mixing efficiencies. This study shows that the spiral ACET
      micropump design can rapidly drive the high-conductivity fluids and efficiently
      mix samples simultaneously. The numerical simulation of the spiral ACET micropump
      is of significant importance for practical, chemical and biological applications,
      and feasible fabrication techiniques should be experimentally investigated in
      future studies.

PMID- 30194860
TI  - Has the red sheep tick, Haemaphysalis punctata, recently expanded its range in
      England?
AB  - The red sheep tick, Haemaphysalis punctata (Ixodida: Ixodidae), has been reported
      as present in the U.K. for more than a century; however, very little has been
      written about its distribution. In recent years, numbers of detections of this
      tick species reported to the Public Health England (PHE) Tick Surveillance Scheme
      have increased. This rise in the number of records may be attributable to
      increased tick surveillance activities or to the increased distribution of this
      species of tick in parts of England. This paper reviews published reports of H.
      punctata and all data held by the Biological Records Centre and PHE, and
      summarizes a number of field studies conducted by PHE and the Animal and Plant
      Health Agency over the past 8 years. It would appear from the evidence presented
      here that H. punctata may be expanding its range across the eastern part of the
      South Downs National Park, where there have also been reports of this tick
      species biting humans. It is possible that the movement of sheep between
      grassland sites is facilitating this spread. Further studies that better
      elucidate the ecology of this tick and its possible role as a vector of human and
      veterinary diseases are now warranted.

PMID- 30194861
TI  - Continuous lumbar drainage and the postoperative complication rate of open
      anterior skull base surgery.
AB  - OBJECTIVES/HYPOTHESIS: Anterior skull base operations pose the risk for
      postoperative cerebrospinal fluid (CSF) leak. Routine lumbar continuous drainage
      catheter (LD) placement is intended to decrease CSF leaks and central nervous
      system (CNS) complications, but there are no sound evidence-based data on its
      efficacy. The primary goal of this study was to review CNS complications
      following anterior open skull base surgery and their association with LD
      placement. The secondary goal was to define predictors for the development of
      early CNS complications. STUDY DESIGN: Retrospective case series. METHODS: We
      conducted a retrospective analysis of all patients who underwent anterior skull
      base surgery between 2000 and 2016 at the Tel Aviv Sourasky Medical Center, an
      Israeli tertiary referral center. RESULTS: A total of 226 patients underwent open
      skull base surgery, of whom 118 had elective perioperative continuous LD
      insertion and 108 did not. Delayed complications were defined as those occurring
      more than 30 days after the index operation. Thirty-one (26%) patients in the LD
      group had early CNS complications compared with only two (1.6%) in the non-LD
      group, whereas 13 (11%) of the former patients had late CNS complications
      compared with four (3%) of the latter patients. Early systemic and late wound
      complications were also significantly more numerous in the LD group. On
      multivariate analysis, elective LD insertion and intracranial tumor extension
      were found to be predictors for developing early CNS complications. CONCLUSIONS:
      The placement of continuous LDs might increase the risk of developing early and
      late CNS complications after open anterior skull base surgery. LEVEL OF EVIDENCE:
      4 Laryngoscope, 2018.

PMID- 30194862
TI  - Rigor and reproducibility in genetic research on eating disorders.
AB  - OBJECTIVE: We explored both within-method and between-method rigor and
      reproducibility in the field of eating disorders genetics. METHOD: We present
      critical evaluation and commentary on component methods of genetic research
      (family studies, twin studies, molecular genetic studies) and discuss both
      successful and unsuccessful efforts in the field. RESULTS: Eating disorders
      genetics has had a number of robust results that converge across component
      methodologies. Familial aggregation of eating disorders, twin-based heritability
      estimates of eating disorders, and genome-wide association studies (GWAS) all
      point toward a substantial role for genetics in eating disorders etiology and
      support the premise that genes do not act alone. Candidate gene and linkage
      studies have been less informative historically. DISCUSSION: The eating disorders
      field has entered the GWAS era with studies of anorexia nervosa. Continued growth
      of sample sizes is essential for rigorous discovery of actionable variation.
      Molecular genetic studies of bulimia nervosa, binge-eating disorder, and other
      eating disorders are virtually nonexistent and lag seriously behind other major
      psychiatric disorders. Expanded efforts are necessary to reveal the fundamental
      biology of eating disorders, inform clinical practice, and deliver new
      therapeutic targets.

PMID- 30194863
TI  - Perceptions of Electronic Health Records Within Otolaryngology Residents Compared
      to Practicing Otolaryngologists.
AB  - OBJECTIVE: This study investigated the perceived impact of electronic health
      records (EHR) on otolaryngology residents with regard to education, patient care,
      and workflow, and then compared the trends with those of practicing
      otolaryngologists. METHODS: A descriptive, cross-sectional survey was developed
      for each core study group: the otolaryngology resident group (ORG) and the
      practicing otolaryngologist group (POG). In total, 536 surveys were submitted: 33
      from the ORG survey and 510 from the POG survey. Response rates were 51.5% and
      21.3%, respectively. RESULTS: Within the two study groups, ORG reported a
      predominately neutral response relating to the impact of EHR on experience
      compared with the POG, which reported far more negative responses. The most
      negative reported change in the ORG related to feeling more like a passive
      observer and scribe in terms of how EHR negatively impacted the role of resident.
      Within the POG group, the majority of negative responses were recorded on the
      impact of EHR on practice efficiency, practice overhead, and number of employees
      required to maintain practice function. CONCLUSION: With otolaryngologists making
      up 1.1% of the U.S. physician workforce in 2015, it is likely that software
      programing of EHR underrepresents the workflow needs of otolaryngologists at this
      time. Future studies investigating the impact of EHR on otolaryngology patient
      care and resident education are needed in the future. LEVEL OF EVIDENCE: V.
      Laryngoscope, 2018.

PMID- 30194864
TI  - The role of quality-of-life instruments in predicting voice therapy dropout.
AB  - OBJECTIVES/HYPOTHESIS: Voice therapy (VT) is essential to the successful
      management of voice disorders. Despite this, two-thirds of patients drop out of
      therapy before completion. In this study we examine whether responses to specific
      question items or domains from the Voice Handicap Index (VHI) are associated with
      VT compliance. STUDY DESIGN: Single-institution retrospective cohort study.
      METHODS: All patients presented to a tertiary care center between January 2011
      and June 2016 with dysphonia. Patients were excluded if seen by speech language
      pathology (SLP) for preoperative assessment only, there was no order for therapy,
      or there was no documentation of therapy performed at outside facilities. Data
      collected included VHI responses, demographics, diagnosis, social history, and
      clinical exam. Patients were divided into three groups for analysis: 1) did not
      attend therapy, 2) partially completed therapy, or 3) completed therapy. RESULTS:
      Of 489 patients referred for VT, 36.2% did not attend, 36.0% partially completed
      VT, and 27.8% completed VT. Patients who did not attend had significantly lower
      scores in VHI, VHI-10, and each of the VHI domains. There was a significant
      difference in age between VT groups, with those electing to not attend
      representing older age. Patients who attended VT were more likely to use their
      voice for work (P = .015). There were statistically significant differences among
      the groups for six VHI question items. CONCLUSIONS: Understanding patient
      motivations, whether a patient uses their voice for work, and specific responses
      to the VHI questionnaire may allow clinicians to better understand patient
      engagement in voice therapy. LEVEL OF EVIDENCE: 4 Laryngoscope, 2018.

PMID- 30194865
TI  - Sodium and potassium conductances in principal neurons of the mouse piriform
      cortex: a quantitative description.
AB  - KEY POINTS: The primary olfactory (or piriform) cortex is a promising model
      system for understanding how the cerebral cortex processes sensory information,
      although an investigation of the piriform cortex is hindered by a lack of
      detailed information about the intrinsic electrical properties of its component
      neurons. In the present study, we quantify the properties of voltage-dependent
      sodium currents and voltage- and calcium-dependent potassium currents in two
      important classes of excitatory neurons in the main input layer of the piriform
      cortex. We identify several classes of these currents and show that their
      properties are similar to those found in better-studied cortical regions. Our
      detailed quantitative descriptions of these currents will be valuable to
      computational neuroscientists who aim to build models that explain how the
      piriform cortex encodes odours. ABSTRACT: The primary olfactory cortex (or
      piriform cortex, PC) is an anatomically simple palaeocortex that is increasingly
      used as a model system for investigating cortical sensory processing. However,
      little information is available on the intrinsic electrical conductances in
      neurons of the PC, hampering efforts to build realistic computational models of
      this cortex. In the present study, we used nucleated macropatches and whole-cell
      recordings to rigorously quantify the biophysical properties of voltage-gated
      sodium (NaV ), voltage-gated potassium (KV ) and calcium-activated potassium (KCa
      ) conductances in two major classes of glutamatergic neurons in layer 2 of the
      PC, semilunar (SL) cells and superficial pyramidal (SP) cells. We found that SL
      and SP cells both express a fast-inactivating NaV current, two types of KV
      current (A-type and delayed rectifier-type) and three types of KCa current (fast
      , medium- and slow-afterhyperpolarization currents). The kinetic and voltage
      dependent properties of the NaV and KV conductances were, with some exceptions,
      identical in SL and SP cells and similar to those found in neocortical pyramidal
      neurons. The KCa conductances were also similar across the different types of
      neurons. Our results are summarized in a series of empirical equations that
      should prove useful to computational neuroscientists seeking to model the PC.
      More broadly, our findings indicate that, at the level of single-cell electrical
      properties, this palaeocortex is not so different from the neocortex, vindicating
      efforts to use the PC as a model of cortical sensory processing in general.

PMID- 30194867
TI  - Protopanaxatriol inhibits melanin synthesis through inactivation of the pCREB
      MITF-tyrosinase signalling pathway in melanocytes.
AB  - Ginsenosides are major active components of ginseng, and have diverse
      pharmacological properties in traditional medicine. Recent reports have shown
      that ginsenosides modify skin physiology and mitigate skin disorders such as
      photoageing and hyperpigmentation. We evaluated the antimelanogenic efficacy of
      protopanaxatriol, a major category of ginsenosides, as a depigmenting agent.
      Protopanaxatriol significantly reduced intracellular and extracellular melanin
      content in a concentration-dependent manner in B16 melanoma cells treated with
      alpha-melanocyte-stimulating hormone. In normal human epidermal melanocytes,
      protopanaxatriol clearly decreased melanin synthesis and dendrite elongation. In
      addition, protopanaxatriol dramatically suppressed the expression of genes
      encoding the melanogenic proteins tyrosinase, tyrosinase-related protein-1 and 
      2, and microphthalmia-associated transcription factor through dephosphorylation
      of cAMP response element-binding protein. These results suggest that
      protopanaxatriol could be an effective candidate anti-melanogenic agent.

PMID- 30194866
TI  - Sequential HLA-haploidentical transplantation utilizing post-transplantation
      cyclophosphamide for GvHD prophylaxis in high-risk and relapsed/refractory
      AML/MDS.
AB  - This study evaluates the role of sequential therapy in HLA-haploidentical
      transplantation (haplo-HSCT) of high-risk, relapsed/refractory AML/MDS. We
      analyzed the course of 33 adults with active disease at time of transplantation
      (AML n = 30; MDS n = 3; median age 58 years, range: 32-71). Sequential therapy
      consisted of cytoreductive chemotherapy (FLAMSA n = 21; clofarabine n = 12)
      applied shortly prior to reduced intensity conditioning for T-cell-replete haplo
      HSCT using post-transplantation cyclophosphamide as GvHD prophylaxis. No graft
      rejection was observed. Complete remission at day +30 was achieved in 97% of
      patients. CI of acute GvHD grade II-IV and chronic GvHD was 24% (no grade IV) and
      23%, respectively. NRM at 1 and 3 years was 15%, each. Severe regimen-related
      toxicities (grade III-IV) were observed in 58%, predominantly involving the
      gastrointestinal tract (diarrhea 48%, mucositis 15%, transient elevation of
      transaminases 18%). Probability of relapse at 1 and 3 years was 28% and 35%. At a
      median follow-up of 36 months, the estimated 1- and 3-year overall survival was
      56% and 48%. Disease-free survival was 49% and 40%, respectively. At 3 years,
      GvHD and relapse-free survival (GRFS) was 24% while chronic GvHD and relapse-free
      survival (CRFS) was 29%. Thus, our results indicate that sequential haplo-HSCT is
      an effective salvage treatment providing high anti-leukemic activity, favorable
      tolerance, and acceptable toxicity in patients suffering from advanced AML/MDS.

PMID- 30194868
TI  - Biological variation of routine haematology and biochemistry measurands in the
      horse.
AB  - BACKGROUND: Clinical pathology results are typically interpreted by referring to
      population-based reference intervals. The use of individualised (subject-based)
      reference intervals is more appropriate for measurands with a high degree of
      variation between individuals. OBJECTIVES: To determine the biological variation
      of routinely analysed equine haematology and biochemistry measurands and
      calculate indices of individuality and reference change values which enable
      production of individualised reference intervals, in a group of healthy,
      privately owned horses. STUDY DESIGN: In a prospective cohort study, thirty-nine
      privately owned horses were sampled by jugular venipuncture for analysis of
      haematology and biochemistry measurands at weekly intervals for 6 weeks. METHODS:
      Haematology was analysed on the day of collection. Serum was frozen and
      biochemistry analyses performed on thawed samples. Duplicate results were
      obtained and the coefficient of variation was calculated for analytical
      variation, within-subject variation and between-subject variation. The index of
      individuality and reference change value were derived for each measurand.
      RESULTS: Haematology (red blood cell count, mean corpuscular haemoglobin and mean
      cell volume) and biochemistry measurands (total protein, globulins, albumin,
      gamma-glutamyl transferase, aspartate aminotransferase) demonstrated high
      individuality, indicating that individualised reference intervals are more
      appropriate for evaluation of these measurands. Two haematology (mean corpuscular
      haemoglobin concentration and platelets) and three biochemistry measurands
      (chloride, glucose and sodium) had low individuality, indicating that the use of
      traditional population-based reference intervals is appropriate for these
      measurands. Remaining measurands had intermediate individuality suggesting
      interpretation of the reference change value should occur with consideration of
      the population-based reference interval. MAIN LIMITATIONS: The use of privately
      owned horses, variable management and environmental factors. CONCLUSIONS: The use
      of individualised reference intervals is justified for many measurands in horses,
      supporting the use of serial sampling, consideration of biological variation and
      application of reference change values for improved clinical decision making and
      patient management in equine practice.

PMID- 30194869
TI  - A rice PHD-finger protein OsTITANIA, is a growth regulator that functions through
      elevating expression of transporter genes for multiple metals.
AB  - Essential metal absorption for plant growth is mediated predominantly by metal
      specific transporters, with expression that responds to the environmental or
      cellular conditions of specific metals. Differing from metal-specific regulation,
      we describe a constitutively expressed transcription factor that regulates the
      transport of several metals in rice. We characterized the rice mutant LOW CADMIUM
      5 (LC5), which exhibited reduced growth and accumulation of essential metals
      (e.g., copper [Cu], zinc [Zn] and manganese [Mn]) in shoots. LC5 was dwarf and
      developed less tillers than the wild type, but the structure of vasculature was
      apparently normal. Molecular genetic analysis revealed that the causal gene of
      LC5 is an ortholog of the transcriptional regulator Arabidopsis thaliana TITANIA
      (TTA), known as a transcriptional regulator. Expression analyses demonstrated
      that the OsTTA gene encodes a nucleus-localized protein containing a plant
      homeodomain-finger (PHD-finger) domain and is expressed ubiquitously in rice
      plants. RNA sequencing and quantitative PCR analyses revealed that the mRNA
      accumulation of transporter genes for essential metals, including iron (Fe), Zn,
      or Mn, were substantially lower in LC5 roots than in the wild type. Unlike known
      transcription factors of metal transport regulation, OsTTA transcript
      accumulation was not affected by metal availability. In addition, the growth
      defect of LC5 was partially rescued by Fe, Zn, or Mn supplementation,
      respectively. Taken together, OsTTA is a constitutively expressed regulator of
      multiple metal transporter genes responsible for essential metals delivery to
      shoots for their normal growth.

PMID- 30194870
TI  - New Insight Regarding the Zygomaticus Minor as Related to Cosmetic Facial
      Injections.
AB  - The present study aimed to determine the arrangement and terminal attachments of
      the zygomaticus minor (Zmi) muscle fibers connecting the orbital and mouth
      regions. The Zmi was examined in 32 specimens of embalmed Korean adult cadavers.
      The Zmi was present in all 32 specimens (100%). In 31 of the specimens (96.9%),
      the Zmi that inserted into the upper lip was formed by muscle fibers that arose
      from the zygomatic bone and muscle fibers that extended from the orbicularis
      oculi (OOc) muscle. In 14 of the specimens (43.8%), some fibers of the Zmi that
      arose from the zygomatic bone blended with the inferior margin of the OOc, while
      the other fibers inserted into the upper lip. After the Zmi fibers blended with
      the inferior margin of the OOc, these fibers constituted the inferior and medial
      margins of the OOc. These fibers were then attached to the medial palpebral
      ligament, the maxilla, the levator labii superioris alaeque nasi muscle, and the
      depressor supercilii muscle. In 30 of 32 specimens (93.8%), muscle fibers that
      extended from the OOc constituted the lateral margin of the Zmi, usually
      descending to the level between the nasal ala and the vermilion border of the
      upper lip and inserting into the upper lip. The obtained data will be helpful for
      understanding their connected movements and in kinematics and electromyographic
      analyses, therapies involving injections of botulinum toxin Type A, and various
      types of facial surgery. Clin. Anat. 31:974-980, 2018. (c) 2018 Wiley
      Periodicals, Inc.

PMID- 30194872
TI  - A novel nacre matrix protein hic24 in Hyriopsis cumingii is essential for calcium
      carbonate nucleation and involved in pearl formation.
AB  - Matrix proteins play important roles in molluscan shell biomineralization, which
      helps in the understanding of mechanisms associated with pearl formation. In this
      study, we characterized the gene encoding a novel shell-matrix protein, hic24, in
      Hyriopsis cumingii and investigated its structure and function. The full cDNA
      sequence of hic24 is 756 bp, with an open reading frame of 654 bp encoding 217
      amino acids, including a signal peptide of 18 amino acids. Sequence analysis
      revealed that the protein is ~23.5 kDa, and that Gly accounted for 11.5% of the
      total amino acid content. Secondary structure prediction indicated a structure
      comprised predominantly by beta-folds. Quantitative real-time polymerase chain
      reaction and in situ hybridization indicated that hic24 is expressed in the
      dorsal epithelial cells of the mantle, indicating hic24 as a nacreous-layer
      matrix protein. Additionally, hic24 expression patterns during pearl
      biomineralization showed that hic24 regulates the growth of the later nacreous
      layer. After attenuating hic24 expression by RNA interference in the mantle, we
      observed that hic24 plays a role in biomineralization of the shell nacre by
      inhibiting calcium carbonate nucleation.

PMID- 30194871
TI  - Trispyrazolylborate Ligands Supported on Vinyl Addition Polynorbornenes and Their
      Copper Derivatives as Recyclable Catalysts.
AB  - Polynorbornenes prepared by vinyl addition polymerization and bearing pendant
      alkenyl groups serve as skeletons to support trispyrazolylborate ligands (Tpx )
      built at those alkenyl sites. Reaction with CuI in acetonitrile led to VA-PNB-Tpx
      Cu(NCMe) (VA-PBN=vinyl addition polynorbornene) with a 0.8-1.4 mmol incorporation
      of Cu per gram of polymer. The presence of tetracoordinated copper(I) ions was
      been assessed by FTIR studies on the corresponding VA-PNB-Tpx Cu(CO) adducts, in
      agreement with those on discrete Tpx Cu(CO). The new materials were employed as
      heterogeneous catalysts in several carbene- and nitrene-transfer reactions,
      showing a behavior similar to that of the homogeneous counterparts but also being
      recycled several times maintaining a high degree of activity and selectivity.
      This is the first example of supported Tpx ligands onto polymeric supports with
      catalytic applications.

PMID- 30194873
TI  - Milia-like idiopathic calcinosis cutis and plaque-type syringoma in a girl with
      Down syndrome.

PMID- 30194874
TI  - Seizure evolution can be characterized as path through synaptic gain space of a
      neural mass model.
AB  - Physiologically based models could facilitate better understanding of mechanisms
      underlying epileptic seizures. In this paper, we attempt to reveal the dynamic
      evolution of intracranial EEG activity during epileptic seizures based on
      synaptic gain identification procedure of a neural mass model. The distribution
      of average excitatory, slow and fast inhibitory synaptic gain in the parameter
      space and their temporal evolution, i.e., the path through the model parameter
      space, were analyzed in thirty seizures from ten temporal lobe epileptic
      patients. Results showed that the synaptic gain values located roughly on a plane
      before seizure onset, dispersed during seizure and returned to the plane when
      seizure terminated. Cluster analysis was performed on seizure paths and
      demonstrated consistency in synaptic gain evolution across different seizures
      from the individual patient. Furthermore, two patient groups were identified,
      each one corresponding to a specific synaptic gain evolution in the parameter
      space during a seizure. Results were validated by a bootstrapping approach based
      on comparison with random paths. The differences in the path revealed variations
      in EEG dynamics for patients despite showing identical seizure onset pattern. Our
      approach may have the potential to classify the epileptic patients into subgroups
      based on different mechanisms revealed by subtle changes in synaptic gains and
      further enable more robust decisions regarding treatment strategy.

PMID- 30194875
TI  - Nav1.5 in astrocytes plays a sex-specific role in clinical outcomes in a mouse
      model of multiple sclerosis.
AB  - Astrogliosis is a hallmark of neuroinflammatory disorders such as multiple
      sclerosis (MS). A detailed understanding of the underlying molecular mechanisms
      governing astrogliosis might facilitate the development of therapeutic targets.
      We investigated whether Nav1.5 expression in astrocytes plays a role in the
      pathogenesis of experimental autoimmune encephalomyelitis (EAE), a murine model
      of MS. We created a conditional knockout of Nav1.5 in astrocytes and determined
      whether this affects the clinical course of EAE, focal macrophage and T cell
      infiltration, and diffuse activation of astrocytes. We show that deletion of
      Nav1.5 from astrocytes leads to significantly worsened clinical outcomes in EAE,
      with increased inflammatory infiltrate in both early and late stages of disease,
      unexpectedly, in a sex-specific manner. Removal of Nav1.5 in astrocytes leads to
      increased inflammation in female mice with EAE, including increased astroglial
      response and infiltration of T cells and phagocytic monocytes. These cellular
      changes are consistent with more severe EAE clinical scores. Additionally, we
      found evidence suggesting possible dysregulation of the immune response
      particularly with regard to infiltrating macrophages and activated microglia-in
      female Nav1.5 KO mice compared with WT littermate controls. Together, our results
      show that deletion of Nav1.5 from astrocytes leads to significantly worsened
      clinical outcomes in EAE, with increased inflammatory infiltrate in both early
      and late stages of disease, in a sex-specific manner.

PMID- 30194876
TI  - Characteristics and prescribing practices of clinicians recently waivered to
      prescribe buprenorphine for the treatment of opioid use disorder.
AB  - BACKGROUND AND AIMS: Expanding access to medication-assisted treatment with
      buprenorphine is a cornerstone of the opioid crisis response, yet buprenorphine
      remains underutilized. Research has identified multiple barriers to prescribing
      buprenorphine. This study aimed to examine clinician characteristics, prescribing
      practices and barriers and incentives to prescribing buprenorphine among
      clinicians with a federal Drug Addiction Treatment Act of 2000 (DATA) waiver to
      prescribe buprenorphine for opioid use disorder treatment. DESIGN: Electronic
      survey of 4225 clinicians conducted between March and April 2018. SETTING: United
      States. PARTICIPANTS: Clinicians obtaining an initial federal DATA waiver or an
      increase in authorized patient limit to prescribe buprenorphine for opioid use
      disorder treatment in 2017. MEASUREMENTS: Descriptive statistics and
      multivariable logistic regression examined clinician characteristics, prescribing
      practices and primary barriers and incentives to prescribing buprenorphine or
      prescribing at or near the authorized patient limit. FINDINGS: Among respondents,
      75.5% had prescribed buprenorphine since obtaining a DATA waiver; the mean
      (standard deviation) number of patients treated in the past month was 26.6
      (40.3), and 13.1% of providers were prescribing at or near their patient limit in
      the past month. Lack of patient demand, cited by 19.4% of clinicians, was the
      most common primary barrier to prescribing buprenorphine or prescribing to the
      authorized patient limit, followed by time constraints in practice (14.6%) and
      insurance reimbursement, prior authorization or other insurance requirements
      (13.2%). Increased patient demand (22.2%), institutional support for
      buprenorphine treatment (12.5%) and increased reimbursement (12.2%) were the most
      endorsed primary incentives for buprenorphine prescribing. Multivariable logistic
      regression models identified multiple clinician characteristics associated with
      buprenorphine prescribing and prescribing at or near the authorized patient
      limit. CONCLUSIONS: US clinicians recently waivered to prescribe buprenorphine
      for opioid use disorder treatment appear to prescribe well below their patient
      limit, and many do not prescribe at all.

PMID- 30194877
TI  - Adventitial cysts of the radial artery are joint connected.
AB  - Volar radial wrist masses are common. Adventitial cysts of the radial artery are
      rarely reported and poorly understood. We describe a case series of adventitial
      cysts in association with the radial artery and detail their pathophysiology and
      treatment. We conducted an Institutional Review Board-approved retrospective
      review of patients treated at our institution from 1997 to 2018. Twelve patients
      were identified. Presenting symptoms typically included pain and swelling over
      the volar radial wrist. High-resolution magnetic resonance imaging (MRI)
      demonstrated tubular, cystic lesions within the adventitia of the radial artery
      with connections to the wrist joint confirmed on multiplanar imaging:
      (radiocarpal joint = 10; scaphotrapeziotrapezoidal joint = 1; and intercarpal
      joint = 1). Seven patients underwent operation, at which time the cyst was
      resected and the articular branch disconnected. These patients reported
      resolution of their symptoms without clinical recurrence. The consistent finding
      of a joint connection in these cases of adventitial cysts associated with the
      radial artery has important clinical implications. The joint connection needs to
      be disconnected. Level of evidence: Level IV, case series. Clin. Anat., 2018. (c)
      2018 Wiley Periodicals, Inc.

PMID- 30194878
TI  - Modulation of trophoblast function by concurrent hyperglycemia and
      antiphospholipid antibodies is in part TLR4-dependent.
AB  - PROBLEM: While diabetes and APS are individually associated with increased risk
      of poor perinatal outcomes, in particular preeclampsia, recent studies have
      demonstrated an association between concurrent aPL and diabetes leading to an
      increased risk of pregnancy morbidity. Hyperglycemia and aPL have independently
      been shown to alter human trophoblast function by inducing a pro-inflammatory,
      anti-angiogenic, and antimigratory response. However, little is known about the
      effects of concurrent hyperglycemia and aPL on trophoblast function. METHOD OF
      STUDY: A human first-trimester extravillous trophoblast cell line was exposed to
      glucose at 5 mmol/L (normoglycemia) or 25 mmol/L (hyperglycemia), all in the
      presence or absence of low-dose aPL or control IgG. For some experiments, the
      TLR4 antagonist, LPS-RS, was included. Cell culture supernatants were measured
      for inflammatory IL-1beta and IL-8, and angiogenic PlGF, sFlt-1, and sEndoglin by
      ELISA. Inflammasome-associated uric acid was measured using a bioassay; caspase-1
      was measured using an activity assay. Trophoblast migration was quantified using
      a two-chamber colorimetric assay. RESULTS: Compared to excess glucose alone,
      combination excess glucose and low-dose aPL (a) further augmented trophoblast
      inflammatory IL-1beta, inflammasome-associated uric acid and caspase-1, and pro
      angiogenic PlGF; (b) dampened trophoblast inflammatory IL-8, anti-angiogenic
      sEndoglin, and sFlt-1; and (c) further reduced trophoblast migration. CONCLUSION:
      Our findings indicate that while concurrent aPL and hyperglycemia are overall
      detrimental to trophoblast function, the presence of two simultaneous insults
      triggers some protective effects.

PMID- 30194879
TI  - Psychosocial safety climate, workplace violence and self-rated health: A multi
      level study among hospital nurses.
AB  - AIMS: To validate the Chinese version Psychosocial Safety Climate scale (PSC-12),
      and examine the associations between PSC, workplace violence and self-rated
      health (SRH). BACKGROUND: Psychosocial safety climate moderates the negative
      effect of workplace violence on health. To address workplace violence experienced
      by nurses across the Asia-Pacific region, it is important to develop and apply a
      Chinese language version of the tool. METHODS: We conducted a two-part study. In
      the first part, the Chinese version PSC-12 was developed and tested for its
      validity in 405 nurses. In the second part, a total of 1690 nurses from 73
      hospitals filled a questionnaire concerning their work and health conditions.
      Multi-level modelling was used to examine the association between PSC, workplace
      violence and SRH. RESULTS: A comparable validity and reliability of the Chinese
      version PSC-12 with the original PSC was found. PSC scores were negatively
      associated with workplace violence. In the hierarchical linear model,
      participants from hospitals with the lowest PSC score had twofold risks of having
      poor SRH. CONCLUSIONS: The Chinese version PSC-12 is a valid tool. Hospital-level
      PSC was associated with poor health status in female nurses. IMPLICATIONS FOR
      NURSING MANAGEMENT: Psychosocial safety climate should be evaluated and promoted
      to prevent workplace violence in nurses.

PMID- 30194880
TI  - Real-time cardiovascular MR with spatio-temporal artifact suppression using deep
      learning-proof of concept in congenital heart disease.
AB  - PURPOSE: Real-time assessment of ventricular volumes requires high acceleration
      factors. Residual convolutional neural networks (CNN) have shown potential for
      removing artifacts caused by data undersampling. In this study, we investigated
      the ability of CNNs to reconstruct highly accelerated radial real-time data in
      patients with congenital heart disease (CHD). METHODS: A 3D (2D plus time) CNN
      architecture was developed and trained using synthetic training data created from
      previously acquired breath hold cine images from 250 CHD patients. The trained
      CNN was then used to reconstruct actual real-time, tiny golden angle (tGA) radial
      SSFP data (13 * undersampled) acquired in 10 new patients with CHD. The same real
      time data was also reconstructed with compressed sensing (CS) to compare image
      quality and reconstruction time. Ventricular volume measurements made using both
      the CNN and CS reconstructed images were compared to reference standard breath
      hold data. RESULTS: It was feasible to train a CNN to remove artifact from highly
      undersampled radial real-time data. The overall reconstruction time with the CNN
      (including creation of aliased images) was shown to be >5 * faster than the CS
      reconstruction. In addition, the image quality and accuracy of biventricular
      volumes measured from the CNN reconstructed images were superior to the CS
      reconstructions. CONCLUSION: This article has demonstrated the potential for the
      use of a CNN for reconstruction of real-time radial data within the clinical
      setting. Clinical measures of ventricular volumes using real-time data with CNN
      reconstruction are not statistically significantly different from gold-standard,
      cardiac-gated, breath-hold techniques.

PMID- 30194881
TI  - Transcriptomic and functional analysis of cucumber (Cucumis sativus L.) fruit
      phloem during early development.
AB  - The phloem of the Cucurbitaceae has long been a subject of interest due to its
      complex nature and the economic importance of the family. As in a limited number
      of other families, cucurbit phloem is bicollateral, i.e. with sieve tubes on both
      sides of the xylem. To date little is known about the specialized functions of
      the internal phloem (IP) and external phloem (EP). Here, a combination of
      microscopy, fluorescent dye transport analysis, micro-computed tomography, laser
      capture microdissection and RNA-sequencing (RNA-Seq) were used to study the
      functions of IP and EP in the vascular bundles (VBs) of cucumber fruit. There is
      one type of VB in the peduncle, but four in the fruit: peripheral (PeVB), main
      (MVB), carpel (CVB) and placental (PlVB). The VBs are bicollateral, except for
      the CVB and PlVB. Phloem mobile tracers and 14 C applied to leaves are
      transported primarily in the EP, and to a lesser extent in the IP. RNA-Seq data
      indicate preferential gene transcription in the IP related to
      differentiation/development, hormone transport, RNA or protein
      modification/processing/transport, and nitrogen compound metabolism and
      transport. The EP preferentially expresses genes for stimulus/stress, defense,
      ion transport and secondary metabolite biosynthesis. The MVB phloem is
      preferentially involved in photoassimilate transport, unloading and long-distance
      signaling, while the PeVB plays a more substantial role in morphogenesis and/or
      development and defense response. CVB and PlVB transcripts are biased toward
      development of reproductive organs. These findings provide an integrated view of
      the differentiated structure and function of the vascular tissue in cucumber
      fruit.

PMID- 30194882
TI  - TLR7 agonist attenuates acetylcholine-induced, Ca2+ -dependent ionic currents in
      swine tracheal submucosal gland cells.
AB  - NEW FINDINGS: What is the central question of this study? Does Toll-like receptor
      7 (TLR7) have any direct effects on Ca2+ -dependent physiological function of
      tracheal submucosal gland cells? What is the main finding and its importance?
      TLR7 is co-localized with SERCA2 in tracheal submucosal gland cells and causes a
      rapid attenuation of acetylcholine (ACh)-induced, Ca2+ -dependent ionic currents
      through the activation of SERCA2-dependent Ca2+ clearance. TLR7 is abundantly
      expressed in the airways of both swine and healthy human subjects, but is
      significantly downregulated in chronic obstructive pulmonary disease (COPD)
      airways. These findings suggest that a dysfunction of TLR7 in COPD removes the
      brake on ACh-induced serous secretion during viral infections, resulting in
      prolonged airway hypersecretion, and that it is one of the triggers of COPD
      exacerbations. ABSTRACT: Airway surface fluids are mainly secreted from
      submucosal glands (SMGs) and play important roles in the defence of airways via
      the activation of mucociliary transport. Toll-like receptor 7 (TLR7) recognizes
      and eliminates single stranded RNA (ssRNA) viruses through the induction of
      innate immunity. However, there is no obvious connection between TLR7 and mucus
      secretion, aside from TLR7 recognizing ssRNA viruses, which are often associated
      with airway hypersecretion in chronic obstructive pulmonary disease (COPD). Here,
      we investigated whether TLR7 has any direct effects on the Ca2+ -dependent
      physiological function of tracheal SMG cells. Patch-clamp analyses revealed that
      TLR7 ligand inhibited the acetylcholine (ACh)-induced ionic currents in isolated
      tracheal SMG cells. Intracellular calcium assays and pharmacological analyses
      revealed that TLR7 attenuated the transient rises in the intracellular calcium
      concentration evoked by ACh by activating sarco/endoplasmic reticulum Ca2+ 
      ATPase 2 (SERCA2). Immunofluorescence staining and immunohistochemical staining
      revealed that TLR7 was co-localized with SERCA2. These findings suggest that the
      activation of TLR7 during viral infections contributes to the rapid attenuation
      of ACh-induced ionic currents through an increase in SERCA2-dependent Ca2+
      clearance in healthy airway SMG cells. Our study also revealed that TLR7
      expression was significantly downregulated in COPD airways. Based on these
      findings, we speculate that a dysfunction of TLR7 may not only have an adverse
      effect on the elimination of these viruses but also remove the brake on ACh
      induced serous secretion, resulting in prolonged hypersecretion and acting as one
      of the triggers of COPD exacerbations.

PMID- 30194883
TI  - A MADS-box transcription factor regulates a central step in sporulation of the
      oomycete Phytophthora infestans.
AB  - MADS-box transcription factors play significant roles in eukaryotes, but have not
      yet been characterized in oomycetes. Here, we describe a MADS-box protein from
      Phytophthora infestans, which causes late blight of potato. P. infestans and most
      other oomycetes express a single MADS-box gene. PiMADS is not transcribed during
      vegetative growth, but is induced early during asexual sporulation. Its mRNA
      levels oscillate in response to light, which suppresses sporulation. The protein
      was not detected in nonsporulating mycelia, but was found in sporulating mycelia
      and spores. Both mRNA and protein levels decline upon spore germination. A
      similar expression pattern as well as nuclear localization was observed when the
      protein was expressed with a fluorescent tag from the native promoter. Gene
      silencing triggered by a construct expressing 478 nt of MADS sequences indicated
      that PiMADS is required for sporulation but not hyphal growth or plant
      colonization. A comparison of wild type to a silenced strain by RNA-seq indicated
      that PiMADS regulates about 3000 sporulation-associated genes, and acts before
      other genes previously shown to regulate sporulation. Analysis of the silenced
      strain also indicated that the native gene was not transcribed while the
      transgene was still expressed, which contradicts current models for homology
      dependent silencing in oomycetes.

PMID- 30194885
TI  - IL-23 promotes the development of castration-resistant prostate cancer.

PMID- 30194884
TI  - Wound, pressure ulcer and burn guidelines - 2: Guidelines for the diagnosis and
      treatment of pressure ulcers, second edition.

PMID- 30194886
TI  - Outcomes of Collaborative and Interdisciplinary Palliative Education for
      Healthcare Assistants: A Qualitative Metasummary.
AB  - AIM: To explore collaborative and interdisciplinary palliative educational
      strategies and corresponding outcomes for healthcare assistants. BACKGROUND:
      Healthcare assistants are frontline staff who provide almost all hands-on care to
      seniors. Healthcare managers are responsible to provide ongoing support and a
      working environment conducive to healthcare assistants' abilities to provide
      quality, safe, evidence-based care. EVALUATION: A Qualitative metasummary of
      collaborative and interdisciplinary teaching strategies was conducted following
      guidelines developed by Sandelowski, Barroso and Voils (2007). KEY ISSUES: The
      gold standard of palliative care is interdisciplinary delivery of care, yet
      education is often monodisciplinary. Furthermore, evaluation of interdisciplinary
      continuing education is most often subjective via self-report questionnaires.
      CONCLUSIONS: Findings from 16 articles representing 15 studies conducted between
      2007-2017 were grouped thematically and summarized. Collaborative or
      interdisciplinary palliative interventions offer healthcare assistants
      opportunities to debrief, build their confidence, and critically reflect on the
      importance of psychosocial care for patients, family and colleagues. IMPLICATIONS
      FOR NURSING MANAGEMENT: The metasummary provides six suggestions for managers who
      are considering implementing a collaborative palliative educational workshop and
      draws attention to the need to create contextual changes that support healthcare
      assistants to enact newly acquired knowledge and skills. This article is
      protected by copyright. All rights reserved.

PMID- 30194887
TI  - Improved lung function at age 6 in children born very preterm and fed extra
      protein post discharge.
AB  - BACKGROUND: In very preterm-born children alveolar maturation is challenged and
      lung function is often compromised during childhood. So far, very few studies
      have focused on type of early nutrition and lung function in children born
      preterm. METHODS: This study is a six years follow-up of 281 very preterm-born
      infants (VPI) with a gestational age (GA) < 32+0 weeks. Infants breastfed at
      discharge from hospital were randomized to unfortified (UHM) or fortified (FHM)
      mother's (human) milk, whereas those not breastfed received a preterm formula
      (PF). The intervention lasted until 4 months corrected age. At six years of age
      fractional exhaled nitric oxide (FeNO), airway resistance and occlusion
      measurements with reversibility were performed. Data on predisposition to asthma
      and allergy as well as possible allergic symptoms of the child were obtained with
      questionnaires. RESULTS: Outcome data was fully or partially available on 160
      (66.9%) of 239 children. This included 49 (30.6%) children fed UHM, 58 (36,3%)
      fed FHM, and 53 (33,1%) fed PF. Successful FeNO measurements were obtained in 119
      (74.4%) children and airway resistance measurements in 160. FeNO results were not
      significantly different between feeding groups. Children fed a protein enriched
      diet (FMH/PF) had the lowest, i.e. best, airway resistance; FHM-fed had lower
      values than UHM-fed (p=0.042) before, and PF-fed had significantly lower values
      than UHM-fed after beta-2-agonist inhalation (P=0.050). The tendency of lower
      airway resistance when protein enriched were the same in gender specific
      analyses. In SGA children the same tendency was found between PF- and UHM-fed
      (P=0.007 before and P=0.046 after beta-2-agonist inhalation). All values were
      within reference limits. CONCLUSIONS: Lung function in very preterm-born children
      may improve when fed a protein enriched nutrition post-discharge. This article is
      protected by copyright. All rights reserved.

PMID- 30194888
TI  - Neutral variation does not predict immunogenetic variation in the European
      grayling (Thymallus thymallus)-implications for management.
AB  - Preservation of genetic diversity is critical to successful conservation, and
      there is increasing demand for the inclusion of ecologically meaningful genetic
      information in management decisions. Supportive breeding programmes are
      increasingly implemented to combat declines in many species, yet their effect on
      adaptive genetic variation is understudied. This is despite the fact that
      supportive breeding may interfere with natural evolutionary processes. Here, we
      assessed the performance of neutral and adaptive markers (major
      histocompatibility complex; MHC) to inform management of European grayling
      (Thymallus thymallus), which routinely involves supplementation of natural
      populations with hatchery-reared fish (stocking). This study is the first to
      characterize MH II DAA and DAB loci in grayling and to investigate immune genetic
      variation in relation to management practice in this species. High-throughput
      Illumina sequencing of "introduced," "stocked native" and "non-stocked native"
      populations revealed significantly higher levels of allelic richness and
      heterozygosity for MH markers than microsatellites exclusively in non-stocked
      native populations. Likewise, significantly lower differentiation at the MH II
      than for microsatellites was apparent when considering non-stocked native
      populations, but not stocked populations. We developed a simulation model to test
      the effects of relaxation of selection during the early life stage within
      captivity. Dependent on the census population size and stocking intensity, there
      may be long-term effects of stocking on MH II, but not neutral genetic diversity.
      This is consistent with our empirical results. This study highlights the
      necessity for considering adaptive genetic variation in conservation decisions
      and raises concerns about the efficiency of stocking as a management practice.

PMID- 30194890
TI  - Reply about alarm symptoms in functional gastrointestinal disorders.

PMID- 30194889
TI  - Alcohol consumption behaviors and neurocognitive dysfunction and emotional
      distress in adult survivors of childhood cancer: a report from the Childhood
      Cancer Survivor Study.
AB  - AIMS: To estimate the level of alcohol consumption behaviors in adult survivors
      of childhood cancer and to test associations between alcohol consumption
      behaviors and symptoms of neurocognitive impairment and emotional distress.
      DESIGN: Retrospective cohort study with longitudinal follow-up of self-reported
      health outcomes. SETTING: Childhood Cancer Survivor Study (CCSS), a 26-center
      study of >= 5-year survivors of childhood cancer diagnosed <= 21 years of age
      between 1970 and 1986 in the United States and Canada. PARTICIPANTS: A total of
      4484 adult survivors of childhood cancer [mean (standard deviation) age at
      evaluation = 34.8 (6.1) years; time from diagnosis = 24.8 (4.4) years] and 1651
      sibling controls who completed surveys reporting on alcohol use, neurocognitive
      impairment and emotional distress. MEASUREMENTS: Survivor report of alcohol use
      included age at drinking initiation and quantity and frequency of alcohol
      consumption. Neurocognition was assessed using the CCSS Neurocognitive
      Questionnaire. Emotional distress symptoms were measured using the Brief Symptoms
      Inventory-18 and the Posttraumatic Stress Diagnostic Scale. FINDINGS: After
      adjustment for childhood cancer treatment exposures, including cranial radiation
      therapy, drinking initiation prior to 18 years of age was associated with 30%
      increased risk of subsequent memory problems [risk ratio (RR) = 1.3; 95%
      confidence interval (CI) = 1.1-1.5]. Younger age at drinking initiation was
      associated with future risk of depression (RR = 1.3; 95% CI = 1.1-1.5), anxiety
      (RR = 1.6; 95% CI = 1.3-2.1), and somatization (RR = 1.2; 95% CI = 1.1-1.4).
      Persistent heavy/risky drinking was associated with 80% increased risk of
      persistent psychological distress (RR = 1.8, 95% CI = 1.4-2.3). CONCLUSIONS:
      Drinking initiation during adolescence is associated with modest increased risk
      for memory impairment and emotional distress in adult survivors of childhood
      cancer.

PMID- 30194891
TI  - An RNase P-Based Assay for Accurate Determination of the 5'-Deoxy-5'
      azidoguanosine-Modified Fraction of in Vitro-Transcribed RNAs.
AB  - Chemoenzymatic approaches are important for generating site-specific, chemically
      modified RNAs, a cornerstone for RNA structure-function correlation studies. T7
      RNA polymerase (T7RNAP)-mediated in vitro transcription (IVT) of a DNA template
      containing the G-initiating class III Phi6.5 promoter is typically used to
      generate 5'-chemically modified RNAs by including a guanosine analogue (G
      analogue) initiator in the IVT. However, the yield of 5'-G analogue-initiated RNA
      is often poor and variable due to the high ratios of G analogue:GTP used in IVT.
      We recently reported that a T7RNAP P266L mutant afforded an approximately three
      fold increase in fluorescent 5'-thienoguanosine-initiated pre-tRNACys compared to
      the wild type T7RNAP. We have further explored the use of T7RNAP P266L to
      generate 5'-deoxy-5'-azidoguanosine (az G)-initiated RNA and found that the
      mutant yielded approximately four times more az G-initiated pre-tRNACys than the
      wild type in an IVT containing a 10:1 ratio of az G:GTP. For accurate
      quantitation of the 5'-az G-initiated RNA fraction, we employed RNase P, an
      endonuclease that catalyzes the removal of the 5'-leader in pre-tRNAs.
      Importantly, we show herein how RNase P can be leveraged for assessing 5'-G
      analogue incorporation in any RNA by rendering the target RNA, upon its binding
      to a customized external guide sequence RNA, into an unnatural substrate of RNase
      P. Such an approach in conjunction with T7RNAP P266L-based IVT should aid
      chemoenzymatic methods that are designed to generate 5'-chemically modified RNAs.

PMID- 30194892
TI  - A novel mutation in CDH11, encoding cadherin-11, cause Branchioskeletogenital
      (Elsahy-Waters) syndrome.
AB  - Cadherins are cell-adhesion molecules that control morphogenesis, cell migration,
      and cell shape changes during multiple developmental processes. Until now four
      distinct cadherins have been implicated in human Mendelian disorders, mainly
      featuring skin, retinal and hearing manifestations. Branchio-skeleto-genital (or
      Elsahy-Waters) syndrome (BSGS) is an ultra-rare condition featuring a
      characteristic face, premature loss of teeth, vertebral and genital anomalies,
      and intellectual disability. We have studied two sibs with BSGS originally
      described by Castori et al. in 2010. Exome sequencing led to the identification
      of a novel homozygous nonsense variant in the first exon of the cadherin-11 gene
      (CDH11), which results in a prematurely truncated form of the protein. Recessive
      variants in CDH11 have been recently demonstrated in two other sporadic patients
      and a pair of sisters affected by BSGS. Although the function of this cadherin
      (also termed Osteoblast-Cadherin) is not completely understood, its prevalent
      expression in osteoblastic cell lines and up-regulation during differentiation
      suggest a specific function in bone formation and development. This study
      identifies a novel loss-of-function variant in CDH11 as a cause of BSGS and
      supports the role of cadherin-11 as a key player in axial and craniofacial
      malformations.

PMID- 30194893
TI  - Overexpressing PRMT1 Inhibits Proliferation and Invasion in Pancreatic Cancer by
      Inverse Correlation of ZEB1.
AB  - Pancreatic cancer (PC) is one of the most malign human cancers, with its
      underlying molecular mechanisms largely unknown. In this work, we investigated
      the mechanistic role of protein arginine methyltransferase 1 (PRMT1) gene in PC.
      Expression of PRMT1 in immortal PC cell lines and clinical human PC tumors was
      evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) and
      western blot. In PANC-1 and SW1990 cells, PRMT1 was either downregulated by
      lentiviral-mediated short hairpin RNA (shRNA) or upregulated by overexpression
      plasmid. The effects of PRMT1 downregulation or upregulation on PC proliferation
      and invasion in vitro, and xenograft in vivo, were evaluated. Gene expression of
      PRMT1 downstream target, zinc finger E-box binding homeobox 1 (ZEB1) was measured
      in PRMT1-downregulated PC cells. ZEB1 was also upregulated in PRMT1-downregulated
      PC cells to evaluate its functional role in PRMT1-mediated regulation in PC.
      PRMT1 was downregulated in both PC cell lines and human tumors. PRMT1
      downregulation in PANC-1 and SW1990 cells significantly suppressed cancer
      proliferation and invasion in vitro and xenograft in vivo. However, PRMT1
      overexpression did not have function impact in PC cells. ZEB1 gene expression was
      suppressed in PRMT1-downregulated PC cells. Subsequently, overexpressing ZEB1
      reversed the antitumor effects of PRMT1 downregulation in PC cells. PRMT1 was
      aberrantly upregulated in PC. PRMT1 inhibition, possibly inversely acting through
      ZEB1, might be an effective molecular intervention to inhibit PC growth and
      invasion. (c) 2018 IUBMB Life, 70(10):1032-1039, 2018.

PMID- 30194894
TI  - Color stability of a bis-acryl composite resin subjected to polishing,
      thermocycling, intercalated baths, and immersion in different beverages.
AB  - OBJECTIVE: To evaluate the color of a bis-acryl resin after polishing, aging, and
      colorants. MATERIALS AND METHODS: From the 140 disks obtained, 35 were not
      polished (NP), 35 were polished with 3-MUm (3P), 35 with 3- and 1-MUm (1P), and
      35 with 3-, 1-, and 0.5-MUm sized particles (05P). Five disks of each group were
      thermocycled for 20, 100, and 200 cycles. Sixty disks were thermocycled and kept
      in beverages (tea, wine, and coffee) after four cycles. Sixty disks were immersed
      in the beverages for 24 hours, a week, and a month. The coordinates L*a*b* were
      measured and the color differences were analyzed by ANOVA. The lightness, chroma,
      and hue differences were evaluated by repeated measures ANOVA. Comparisons were
      made with Tukey's test (alpha = 0.05). RESULTS: Similar behaviors were observed
      between 3P and 05P groups (1.53 and 1.95DeltaE00 ) (P < .05). The NP group
      submitted to 200 cycles showed the biggest color differences (3.02) (P = .003).
      The greatest color differences were observed in the NP group submitted to
      immersion in coffee (8.30) and wine (7.93) (P < .05). CONCLUSIONS: The polished
      surfaces were the least stained. Coffee and wine provided the greatest color
      changes, both for baths and immersions. CLINICAL SIGNIFICANCE: Polishing of
      provisional surfaces restorations made of bis-acrylic resin is essential to
      minimize staining caused by aging and use of colorants, regardless of the
      particle size present in the polishing paste. The contact with coffee and red
      wine should be avoided, especially for clinical times greater than 1 week.

PMID- 30194895
TI  - Mechanistic Probes for the Epimerization Domain of Nonribosomal Peptide
      Synthetases.
AB  - Nonribosomal peptide synthetases (NRPSs) are responsible for the synthesis of a
      variety of bioactive natural products with clinical and economic significance.
      Interestingly, these large multimodular enzyme machineries incorporate
      nonproteinogenic d-amino acids through the use of auxiliary epimerization
      domains, converting l-amino acids into d-amino acids that impart into the
      resulting natural products unique bioactivity and resistance to proteases. Due to
      the large and complex nature of NRPSs, several questions remain unanswered about
      the mechanism of the catalytic domain reactions. We have investigated the use of
      mechanism-based crosslinkers to probe the mechanism of an epimerization domain in
      gramicidin S biosynthesis. In addition, MD simulations were performed, showcasing
      the possible roles of catalytic residues within the epimerization domain.

PMID- 30194896
TI  - A two-wave panel study on teachers' emotions and emotional-labour strategies.
AB  - The aim of this study was to examine the reciprocal relations between discrete
      emotions that teachers typically experience while teaching and interacting with
      students (i.e., joy, love, anger, and hopelessness) and emotional labour
      strategies (i.e., deep acting and two forms of surface acting-hiding feelings and
      faking emotions) over time. To address these research aims, two-wave panel design
      and cross-lagged structural equation modeling were implemented. An initial sample
      of 2,022 teachers filled in questionnaires with a time lag of 6 months. The
      results showed that teachers' emotions and emotional labour are related to each
      other over time. Love positively predicted deep acting and anger positively
      predicted hiding feelings and faking emotion over time. The opposite direction of
      association was also established-deep acting positively predicted joy, whereas
      hiding feelings positively predicted hopelessness. The results highlight the
      importance of taking a discrete approach to emotions and triadic approach to
      emotional labour when examining their reciprocal relations and may have important
      practical implications in promoting teachers' emotional well-being.

PMID- 30194897
TI  - Advanced inorganic nanocomposite for decontaminating titanium dental implants.
AB  - Oral hygiene and regular maintenance are crucial for preserving good peri-implant
      health. However, available prophylaxis products and toothpastes, which are
      optimized for cleaning teeth, tend to contaminate and abrade implant surfaces due
      to their organic components and silica microparticles, respectively. This study
      aims to develop an organic-free implant-paste based on two-dimensional
      nanocrystalline magnesium phosphate gel and hydrated silica nanoparticles (20-30%
      w/w) for cleaning oral biofilm on titanium dental implants. The surface
      chemistry, morphology, and bacterial load of contaminated Ti disks before and
      after decontamination using prophylaxis brushing with toothpaste and implant
      paste were characterized by X-ray photoelectron spectroscopy (XPS), scanning
      electron microscopy, and fluorescence spectroscopy. Both commercial toothpastes
      and implant-paste remove bacteria, however, only implant-paste protects Ti metal
      from abrasion and removes organic contaminants. XPS showed a significant decrease
      of carbon contamination from 73% +/- 2 to 20% +/- 2 after mechanical brushing
      with implant-paste compared to 41% +/- 11 when brushing with commercial
      toothpastes (p < 0.05). Fluorescence microscopy revealed that bacteria load on
      biofilm contaminated Ti (44 * 103  +/- 27 * 103 /um2 ) was significantly reduced
      with the implant-paste to 2 * 103  +/- 1 * 102 /um2 and with a commercial
      toothpaste to 2.9 * 103  +/- 7.102 /um2 . This decay is relatively higher than
      the removal achieved using rotary prophylaxis brush alone (5 * 103  +/- 1 * 103
      /um2 , p < 0.05). Accordingly, this novel implant-paste shows a great promise as
      an efficient decontamination approach. (c) 2018 Wiley Periodicals, Inc. J.
      Biomed. Mater. Res. Part B, 2018.

PMID- 30194898
TI  - Novel Podophyllotoxin Derivatives as Potential Tubulin Inhibitors: Design,
      Synthesis, and Antiproliferative Activity Evaluation.
AB  - A number of podophyllotoxin derivatives (3A-3J) had been designed and
      synthesized, and their biological activities were evaluated in this study.
      Moreover, the antiproliferation activities of these compounds against four human
      cancer cell lines (HepG2, HeLa, A549, and MCF-7) were also tested. The results
      indicated that the most promising compound 3D displayed potent inhibitory
      activity over the four human cancer cell lines and was further demonstrated to
      have potent tubulin polymerization inhibitory effects without damaging the non
      cancer cells. Additionally, 3D was verified to effectively interfere with tubulin
      and could prevent the mitosis of cancer cells, leading to cell cycle arrest and
      eventually inducing apoptosis in a dose- and time-dependent manner. Moreover, the
      Western blotting and siRNA results showed that Bcl-2 was downregulated in HepG2
      cells treated with 3D. Finally, the molecular docking simulation results revealed
      that 3D could fit well in the colchicine-binding pocket. Taken together, this
      study has provided certain novel antitubulin agents for possible cancer
      chemotherapy.

PMID- 30194899
TI  - A chromatographic study on the retention behavior of the amylose tris(3-chloro-5
      methylphenylcarbamate) chiral stationary phase under aqueous conditions.
AB  - In this study, the retention properties of the immobilized polysaccharide-derived
      Chiralpak IG-3 chiral stationary phase under aqueous-organic conditions were
      investigated. A systematic evaluation of the retention factors of the enantiomers
      of the chiral sulfoxide oxfendazole, endowed with anthelmintic activity and
      selected as test compound, was carried out changing progressively the water
      content in hydro-organic eluents containing methanol, ethanol or acetonitrile.
      From the results obtained with acetonitrile/water mobile phases and the
      associated retention plots, clear U-shape retention dependencies, indicative of
      the interplay of both hydrophilic interaction liquid chromatography and reversed
      phase modes, were highlighted. A U-turn point of retention mechanism was recorded
      in correspondence of the acetonitrile/water 100:40 v/v mobile phase. Retention
      was significantly affected by small percentages of trifluoroacetic acid or
      diethylamine additives incorporated in the mobile phase. It is worth emphasizing
      that the basic additive was more effective in reducing retention in the reversed
      phase region, while the action of acid additive was more pronounced in the
      hydrophilic interaction liquid chromatography region. Finally, either in the
      transition from hydrophilic interaction liquid chromatography to reversed-phase
      conditions or after additive addition, the enantioselectivity did not vary
      significantly.

PMID- 30194900
TI  - Fabrication of a bilayer scaffold for small diameter vascular applications.
AB  - One of the greatest challenges plaguing cardiovascular tissue engineering has
      been the development of a compliant vascular graft. In this work, we report the
      development of a synthetic vascular graft with compliance similar to native
      arteries at physiological pressures. A bilayer scaffold was fabricated from a
      solid polymeric lumen made from poly(1,8 octanediol-co-citrate) (POC) and a
      microfibrous medial layer composed of type I collagen, elastin, and POC.
      Mechanical analysis revealed dynamic compliance, ~6.9% within 1% of native
      vessels, 5.9%. The burst pressure was an order of magnitude lower than native
      vessels (~400 mmHg vs. ~3000 mmHg) but was above physiological pressure ranges.
      Biocompatibility studies indicated the scaffold posed no acute cytotoxic risk to
      relevant cell types and supported the proliferation of vascular smooth muscle
      cells. In addition, upon exposure of the scaffold to whole blood, there was no
      statistically significant hemolysis, <2%. Overall this is a promising material
      system and scaffold to develop a biodegradable tissue-engineered vascular graft.
      (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2850-2862,
      2018.

PMID- 30194901
TI  - Laparoscopic management of bowel obstruction due to multiple congenital adhesion
      bands in pregnancy - a video vignette.

PMID- 30194903
TI  - Colonoscopic removal of a giant appendiceal faecolith without appendectomy for
      acute appendicitis - a video vignette.

PMID- 30194902
TI  - Adherence to Pediatric Cardiac Arrest Guidelines Across a Spectrum of Fifty
      Emergency Departments: A Prospective, In Situ, Simulation-based Study.
AB  - BACKGROUND AND OBJECTIVES: Pediatric out-of-hospital cardiac arrest survival
      outcomes are dismal (<10%). Care that is provided in adherence to established
      guidelines has been associated with improved survival. Lower mortality rates have
      been reported in higher-volume hospitals, teaching hospitals, and trauma centers.
      The primary objective of this article was to explore the relationship of hospital
      characteristics, such as annual pediatric patient volume, to adherence to
      pediatric cardiac arrest guidelines during an in situ simulation. Secondary
      objectives included comparing adherence to other team, provider, and system
      factors. METHODS: This prospective, multicenter, observational study evaluated
      interprofessional teams in their native emergency department (ED) resuscitation
      bays caring for a simulated 5-year-old child presenting in cardiac arrest. The
      primary outcome, adherence to the American Heart Association pediatric
      guidelines, was assessed using a 14-item tool including three component domains:
      basic life support (BLS), pulseless electrical activity (PEA), and ventricular
      fibrillation (VF). Provider, team, and hospital-level data were collected as
      independent data. EDs were evaluated in four pediatric volume groups (low <
      1,800/year; medium 1,800-4,999; medium-high 5,000-9,999; high > 10,000). Cardiac
      arrest adherence and domains were evaluated by pediatric patient volume and other
      team and hospital-level characteristics, and path analyses were performed to
      evaluate the contribution of patient volume, systems readiness, and teamwork on
      BLS, PEA, and VF adherence. RESULTS: A total of 101 teams from a spectrum of 50
      EDs participated including nine low pediatric volume (<1,800/year), 36 medium
      volume (1,800-4,999/year), 24 medium-high (5,000-9,999/year), and 32 high volume
      (>=10000/year). The median total adherence score was 57.1 (interquartile range =
      50.0-78.6). This was not significantly different across the four volume groups.
      The highest level of adherence for BLS and PEA domains was noted in the medium
      high-volume sites, while no difference was noted for the VF domain. The lowest
      level of BLS adherence was noted in the lowest-volume EDs. Improved adherence was
      not directly associated with higher pediatric readiness survey (PRS) score
      provider experience, simulation teamwork performance, or more providers with
      Pediatric Advanced Life Support (PALS) training. EDs in teaching hospitals with a
      trauma center designation that served only children demonstrated higher adherence
      compared to nonteaching hospitals (64.3 vs 57.1), nontrauma centers (64.3 vs.
      57.1), and mixed pediatric and adult departments (67.9 vs. 57.1), respectively.
      The overall effect sizes for total cardiac adherence score are ED type gamma =
      0.47 and pediatric volume (low and medium vs. medium-high and high) gamma = 0.41.
      A series of path analyses models was conducted that indicated that overall
      pediatric ED volume predicted significantly better guideline adherence, but the
      effect of volume on performance was only mediated by the PRS for the VF domain.
      CONCLUSIONS: This study demonstrated variable adherence to pediatric cardiac
      arrest guidelines across a spectrum of EDs. Overall adherence was not associated
      with ED pediatric volume. Medium-high-volume EDs demonstrated the highest levels
      of adherence for BLS and PEA. Lower-volume EDs were noted to have lower adherence
      to BLS guidelines. Improved adherence was not directly associated with higher PRS
      score provider experience, simulation teamwork performance, or more providers
      with PALS training. This study demonstrates that current approaches optimizing
      the care of children in cardiac arrest in the ED (provider training, teamwork
      training, environmental preparation) are insufficient.

PMID- 30194904
TI  - Adsorption-associated orientational changes of immunoglobulin G and regulated
      phagocytosis of Staphylococcus epidermidis.
AB  - Understanding the adsorption of immunoglobulin G (IgG) on biomaterials surfaces
      is crucial for design and modification of the surfaces to alleviate inflammatory
      responses after implantation. Here, we report direct visualization and two
      dimensional (2D) image interpretation of the IgG molecule adsorbed on simplified
      surfaces by single particle electron microscopy and atomic force microscopy.
      Influence of the orientational changes in adsorbed IgG on phagocytosis of
      macrophages against Staphylococcus epidermidis is further examined. Untreated
      amorphous carbon film and -COOH and -NH2 grafted carbon films are employed as the
      model surfaces for the adsorption testing. Results show that IgG displays flat
      orientation lying on the untreated surface, while forms vertical orientations
      standing on the functionalized surfaces. These specific spatial alignments are
      associated with altered unfolding extent and structure rearrangement of IgG
      domains, which are influenced synergistically by surface charge and wettability
      of the substrata. The changes in interdomain distance of IgG molecules
      subsequently regulate immune behaviors of macrophages and phagocytosis of S.
      epidermidis. The results would give insight into appropriate design of
      biomaterial surfaces in nanoscales for desired inflammatory responses. (c) 2018
      Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2838-2849, 2018.

PMID- 30194905
TI  - IL4 gene VNTR polymorphism in chronic periodontitis in end-stage renal disease
      patients.
AB  - OBJECTIVE: Interleukin-4 gene polymorphisms were found to be associated with
      periodontitis. The purpose of this case-control study was to evaluate association
      of IL4 VNTR polymorphism with periodontitis in patients with end-stage renal
      disease (ESRD). SUBJECTS AND METHODS: We examined 180 ESRD patients with chronic
      periodontitis, 82 without CP and 180 healthy controls. Genomic DNA from all
      subjects was genotyped for the IL4 VNTR polymorphism by polymerase chain reaction
      (PCR). RESULTS: Genotype distribution in all groups followed Hardy-Weinberg
      equilibrium. Significant differences in genotype and allele frequencies were
      observed between groups. The patient group had higher frequency of P1 allele than
      controls, with odds ratio for P1 allele 1.6 (95% CI 1.1-2.3) and P1P1 genotype
      2.73 (95% CI 1.06-7.5). There were no differences in polymorphism distribution
      between ESRD patients without CP and controls. Periodontal disease was more
      severe in older patients (>=50 years). Similarly, patients with T2DM had more
      severe manifestation of CP than patients without diabetes (p = 0.01 for plaque
      index, p = 0.004 for bleeding index and p = 0.03 for gingival index). CONCLUSION:
      Our findings suggest that VNTR polymorphism in IL4 gene might be a risk factor
      for chronic periodontitis in patients with ESRD.

PMID- 30194906
TI  - Bone morphogenic protein expression and bone formation are induced by bioactive
      glass S53P4 scaffolds in vivo.
AB  - The two-stage induced-membrane (IM) technique is increasingly used for treatment
      of large bone defects. In stage one, the bone defect is filled with
      polymethylmethacrylate (PMMA), which induces a membrane around the implant. In
      stage two, PMMA is replaced with bone graft. Bioactive glasses (BAGs) are bone
      substitutes with bone-stimulating and angiogenic properties. We have previously
      shown that a certain type of BAG can also induce a foreign-body membrane similar
      to PMMA. The aim of this study was to evaluate the bone-forming capacity of
      sintered BAG-S53P4 and poly(lactide-co-glycolide) (PLGA)-coated BAG-S53P4
      scaffolds for potential use as bone substitutes in a single-stage IM technique.
      Sintered porous rods of BAG-S53P4, BAG-S53P4-PLGA, or PMMA were implanted in
      rabbit femurs for 2, 4, or 8 weeks. The expression of bone morphogenic protein
      (BMP)-2, -4, and -7 in the IMs of implanted materials were analyzed with real
      time quantitative polymerase chain reaction. Micro-computed tomography imaging
      was used to evaluate bone growth and further verified with scanning electron
      microscopy. BAG-S53P4 and BAG-S53P4-PGLA scaffold IMs show similar or superior
      expression of BMP-2, -4, and -7 compared with PMMA IM. Bone ingrowth into BAG
      scaffolds increased over time. Active bone formation occurred inside the BAG
      scaffolds and the respective BMP expressions were similar or superior for the BAG
      IMs compared with PMMA, thus making BAGs a promising device for single-stage
      treatment of bone defects. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res B
      Part B: Appl Biomater, 2018.

PMID- 30194908
TI  - Complete robotic lateral pelvic node dissection using the da Vinci Xi platform in
      rectal cancer - a video vignette.

PMID- 30194909
TI  - Auxiliary UV light devices for removal of fluorescent resin residues after
      bracket debonding.
AB  - OBJECTIVE: The purpose of this clinical report was to describe the detection of
      fluorescent resin residue after orthodontic bracket debonding with two UV light
      devices and analyze the surface morphology of enamel after 1 year. CLINICAL
      CONSIDERATIONS: A 22-year-old woman had orthodontic brackets removed by a
      previous dentist; however, resin residue was left on the enamel of the maxillary
      teeth. After confirming the fluorescent property of the resin, different
      protocols were used for each half of the maxillary arch. The first method, a
      black light lens was attached to a light-curing device to detect resin
      fluorescence, followed by polishing with silicone rubber tips. The second method
      used a light emitting diode light system attached to and activated by a high
      speed handpiece, followed by polishing with discs. Both methods were completed
      with diamond polishing paste applied with felt discs. Polyvinyl siloxane
      impressions were made initially, after residue removal, after finishing and after
      polishing for morphologic analysis. The results were evaluated with photographs
      and the scanning electron microscope images made of resin casts from the
      impressions. A follow-up was made after 1 year. CONCLUSIONS: Both methods yielded
      a satisfactory clinical outcome, with a smooth surface, acceptable surface gloss
      and minimal tooth wear. The use of a UV device that excites fluorescence is
      recommended for the controlled removal of resin residue on enamel. CLINICAL
      SIGNIFICANCE: The controlled removal of resin residue from enamel after
      orthodontic treatment is challenging but can be improved with auxiliary methods
      for detecting resin residues. This clinical report describes two types of devices
      that excite fluorescent resins in a more rapid and precise technique to guide the
      practitioner in the controlled removal of residual resin on teeth.

PMID- 30194907
TI  - Understanding the pediatric psychiatric phenotype of 22q11.2 deletion syndrome.
AB  - The purpose of this article is to provide an overview of current insights into
      the neurodevelopmental and psychiatric manifestations of 22q11.2 deletion
      syndrome (22q11DS) in children and adolescents. The pediatric neuropsychiatric
      expression of 22q11DS is characterized by high variability, both interindividual
      and intraindividual (different expressions over the lifespan). Besides varying
      levels of intellectual disability, the prevalence of autism spectrum disorders,
      attention deficit disorders, anxiety disorders, and psychotic disorders in young
      individuals with 22q11DS is significantly higher than in the general population,
      or in individuals with idiopathic intellectual disability. Possible explanations
      for this observed phenotypic variability will be discussed, including genetic
      pleiotropy, gene-environment interactions, the age-dependency of phenotypes, but
      also the impact of assessment and ascertainment bias as well as the limitations
      of our current diagnostic classification system. The implications inferred by
      these observations aforementioned bear direct relevance to both scientists and
      clinicians. Observations regarding the neuropsychiatric manifestations in
      individuals with 22q11DS exemplify the need for a dimensional approach to
      neuropsychiatric assessment, in addition to our current categorical diagnostic
      classification system. The potential usefulness of 22q11DS as a genetic model to
      study the early phases of schizophrenia as well as the phenomenon of
      neuropsychiatric pleiotropy observed in many CNV's will be delineated. From a
      clinical perspective, the importance of regular neuropsychiatric evaluations with
      attention to symptoms not always captured in diagnostic categories and of
      maintaining equilibrium between individual difficulties and competencies and
      environmental demands will be discussed.

PMID- 30194910
TI  - Repair of aged bulk-fill composite with posterior composite: Effect of different
      surface treatments.
AB  - OBJECTIVE: In the present study, the ability of posterior resin composite to
      repair aged bulk-fill resin composite and vice versa were assessed by shear bond
      strength testing. MATERIALS AND METHODS: Resin composite substrates were aged and
      surfaces were abraded with abrasive papers, then bulk-fill substrates were
      repaired with posterior resin composite and vice versa using different surface
      treatments (no surface treatment [control]; etching with 37% phosphoric acid [H3
      PO4 ] for 20 seconds; etching with 10% hydrofluoric acid [HF] for 20 seconds;
      etching with 37% H3 PO4 for 20 seconds + adhesive application; etching with 10%
      HF for 20 seconds + adhesive application; adhesive application only). Shear bond
      strengths (SBS) were then measured and surface roughness values (Ra) were
      determined. Cohesive strengths of nonaged resin composites were measured and used
      as reference groups. Resin composite surfaces after acid etching were evaluated
      by SEM. Data were analyzed using ANOVA and Fisher's LSD tests (P < .05). RESULTS:
      ANOVA showed that resin composite repair type did not affect SBS significantly (P
      = .850), while it showed that surface treatments significantly affected the SBS
      (P = .000). Only a combination of etching with 10% HF for 20 seconds with resin
      adhesive application provided similar SBS values with those of the positive
      control. CONCLUSIONS: It was concluded that the aged bulk-fill resin composite
      would be effectively repaired with conventional posterior resin composite or vice
      versa if proper repair protocol was deployed. CLINICAL SIGNIFICANCE: The
      combination of 10% HF etching and adhesive application would provide efficient
      repair strength when the aged bulk fill resin composite is repaired with
      conventional posterior resin composite or vice versa.

PMID- 30194911
TI  - A collaborative, mixed-methods evaluation of a low-cost, handheld 3D imaging
      system for child anthropometry.
AB  - 3D imaging for body measurements is regularly used for design of garments and
      ergonomic products. The development of low-cost 3D scanners provided an
      opportunity to extend the use of 3D imaging to the health sector. We developed
      and tested the AutoAnthro System, the first mobile, low-cost, full-body, 3D
      imaging system designed specifically for child anthropometry. This study
      evaluated the efficiency, invasiveness, and user experience of the AutoAnthro
      System. We used a mixed-methods, collaborative approach that included a
      quantitative time-motion study and qualitative interviews of anthropometrists.
      For cooperative children, anthropometrists considered the use of 3D imaging an
      easy, "streamlined experience," but with uncooperative children, anthropometrists
      reported that capturing a good quality scan was out of their control. The mean
      time to complete a full set of scans was 68 s (standard deviation [SD] 29),
      compared with 135 s (SD 22) for a set of manual measurements (stature, head
      circumference, and arm circumference). We observed that crying was more common
      during manual measurement, and anthropometrist interviews confirmed that 3D
      imaging was less stressful for children than manual measurement. In a previous
      publication, we showed the potential of 3D imaging to produce reliable and
      accurate measurements. In this study, we found that anthropometrists were not
      ready to abandon manual equipment for 3D scanners because of difficulty in
      measuring uncooperative children. Revising the AutoAnthro System to address
      anthropometrists' concerns on capturing good quality scans of uncooperative
      children should help to facilitate widespread use of 3D imaging for child
      anthropometry.

PMID- 30194912
TI  - Activation of the Oxidative Pentose Phosphate Pathway is Critical for
      Photomixotrophic Growth of a hik33-Deletion Mutant of Synechocystis sp. PCC 6803.
AB  - The histidine kinase Hik33 plays a central role in acclimation to changing
      environments in cyanobacteria. Deletion of hik33 induces a strong stress-like
      response in Synechocystis sp. PCC 6803 (Synechocystis) as represented by
      repressed photoautotrophic growth and photosynthesis, and differential expression
      of stress-responsive proteins. In contrast, the photomixotrophic growth of the
      hik33-deletion mutant (Deltahik33) with glucose as the exogenous carbon source is
      only marginally repressed. To investigate how glucose rescues the growth of
      Deltahik33, the proteomes of the photomixotrophically growing wild-type (WT) and
      the mutant strains of Synechocystis are quantitatively analyzed. It is found that
      glucose induces upregulation of the oxidative pentose phosphate (OPP) pathway.
      Depletion of glucose-6-phosphate dehydrogenase (G6PDH), which catalyzes the first
      and the rate-limiting step of the OPP pathway, significantly inhibits the
      photomixotrophic growth of Deltahik33 but not of the WT. The result suggests that
      the OPP pathway, which is usually nonfunctional in the photomixotrophically
      growing WT, plays a major role in the photomixotrophic growth of Deltahik33.

PMID- 30194913
TI  - Longitudinal assessment of stability of sensory features in children with autism
      spectrum disorder or other developmental disabilities.
AB  - : Prior research on the stability of sensory processing problems in children with
      autism spectrum disorder (ASD) or other developmental disabilities (DD) has
      produced inconsistent results. We employed a longitudinal study design to assess
      the stability of three clinical sensory response patterns: hyporesponsiveness;
      hyperresponsiveness; and sensory interests, repetitions, and seeking behaviors
      (SIRS). Parents of children with ASD (n = 55) or DD (n = 35) responded to sensory
      questionnaires at two time points (T1 and T2) separated by 3.3 years on average,
      with the children aged 2-12 years (M = 5.69 +/- 2.46) at the first assessment.
      For each sensory response pattern, regression analysis revealed that, for both
      ASD and DD groups, scores at T1 were strong predictors of scores at T2. Over the
      longitudinal assessment interval, there was a significant mean decline in
      severity for SIRS in both groups and for hyporesponsiveness in the ASD group.
      Parental estimates of the amount of therapy services received were positively
      associated with the severity of sensory features at T2, an outcome that may
      result from increased intervention dosages being administered to children who
      fail to improve over time. The results are discussed in terms of person-centered
      and environmental considerations, which, in combination, have the capacity to
      affect stability outcomes for sensory features. Autism Research 2018. (c) 2018
      Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Children with
      autism spectrum disorder (ASD) and other developmental disabilities (DD) may
      process sensory information differently from those who do not have ASD. For
      example, some children may be over-responsive or under-responsive to sound or
      touch. In this study, we showed that sensory features in preschool/school-aged
      children with ASD and DD tend to decrease on average over a several year period.
      However, individual children tend to retain their ranking (low or high in sensory
      features) in comparison to other children over time.

PMID- 30194914
TI  - Multiple incidence of the prescription diuretic hydrochlorothiazide in compounded
      nutritional supplements.
AB  - Diuretic agents are prohibited in sports in- and out-of-competition according to
      the regulations of the World Anti-Doping Agency (WADA) because of their possible
      masking effects on other doping agents in urine samples, and their ability to
      produce fast acute weight losses. Despite previous studies reported adverse
      analytical findings (AAFs) resulting from contaminations at ppm level (MUg/g) of
      medicinal products, and recommended to introduce reporting limits for diuretics
      in doping controls, these are not adopted in analyses performed by WADA
      accredited laboratories. We report the case of an athlete with two AAFs for
      hydrochlorothiazide (HCTZ) at low urinary concentrations (<10 ng/mL), who
      declared the use of nutritional supplements prepared in a compounding pharmacy.
      His nutritional supplements were analyzed revealing HCTZ presence in different
      concentrations, at the ppm level (MUg/g and ng/mL). With the aim of testing the
      plausibility of the observed urinary HCTZ concentrations with the nutritional
      supplement ingestion, a urinary excretion study with three healthy volunteers was
      performed. HCTZ-contaminated powder (6.4 MUg/g of HCTZ) was administered to each
      subject in different dosages, reproducing the possible ingestion pattern
      occurred. Urine specimens were collected before and after ingestion of the
      powder, up to 24 hours, and underwent liquid-liquid extraction and liquid
      chromatography-tandem mass spectrometry determination. Post-administration
      specimens were found to contain HCTZ at concentrations of 5-230 ng/mL, which
      supported the accidental inadvertent intake of the prohibited substance by the
      athlete. This study makes the argument that the introduction of reporting limits
      for diuretics are warranted in doping control samples, in order to protect
      against inadvertent AAFs due to contaminated products.

PMID- 30194915
TI  - Social network analysis for poultry HPAI transmission.
AB  - In this survey study, the networks among poultry farms and related poultry
      enterprises in two counties in China (Feixi County in Anhui Province and Beizhen
      city in Liaoning Province) were analysed and evaluated focusing on the
      connectivity of contacts, movements, and potential pathogen transmission. The
      Feixi County poultry production network exhibited greater connectivity, which
      incorporated approximately 94% of the farms interviewed in a major component (a
      set of connected farms not linked with each other), mainly due to linkages of
      backyard farms through local produce stores and individual agents, whilst the
      Beizhen City network was more fragmented owing to independent in-house operations
      (from breed, raise, to slaughter and process) of a few large companies, with
      multiple smaller components. A range of factors influencing the
      contacts/movements among farms (act as bridges) were identified in this study.
      Ability to predict the pathway with the network characteristics on the basis of
      the factors, such as entity type and geographic location, is useful for
      developing risk-based approaches for disease prevention, surveillance, early
      detection, and effective controlling.

PMID- 30194916
TI  - Synchronous pancreatic tumors in a patient with history of Wilms tumor: A case of
      pancreatic adenocarcinoma and lipid-rich neuroendocrine tumor diagnosed by
      cytopathology.
AB  - Synchronous tumors represent a very small portion of pancreatic tumors. Although
      there is a higher incidence of secondary malignant neoplasms (SMN) in patients
      with history of Wilms tumor (WT), pancreatic tumors are very infrequent SMNs in
      this population. We report the first case of synchronous pancreatic tumors in a
      patient with history of WT. Two separated pancreatic lesions were identified by
      abdominal computerized tomography (CT) scan. Fine-needle aspiration of both
      lesions was performed for cytopathology examination. A pancreatic adenocarcinoma
      was diagnosed in the head of pancreas, and the pancreatic body lesion was found
      to be a neuroendocrine tumor (NET). The NET had characteristic vacuolated lipid
      rich cytoplasm. Further molecular testing was done on both tumors, but no common
      cancer-associated mutation was found.

PMID- 30194917
TI  - Use of a noninfectious surrogate to predict minute virus of mice removal during
      nanofiltration.
AB  - Viruses can arise during the manufacture of biopharmaceuticals through
      contamination or endogenous expression of viral sequences. Regulatory agencies
      require "viral clearance" validation studies for each biopharmaceutical prior to
      approval. These studies aim to demonstrate the ability of the manufacturing
      process at removing or inactivating virus and are conducted by challenging scaled
      down manufacturing steps with a "spike" of live virus. Due to the infectious
      nature of these live viruses, "spiking studies" are typically conducted in
      specialized biological safety level-2 facilities. The costs and logistics
      associated with these studies limit viral clearance analysis during process
      development and characterization. In this study, a noninfectious Minute Virus of
      Mice-Mock Virus Particle (MVM-MVP) was generated for use as an economical small
      virus spiking surrogate. An immunoglobin G containing solution was spiked with
      live MVM or MVM-MVP and processed through Planova nanofiltration units. Flux
      decay data was collected and particle reduction values were calculated from
      TCID50 and Immuno-qPCR analysis. The data indicated comparable filtration
      performance and particle reduction between infectious MVM and noninfectious
      surrogate, MVM-MVP. This proof of concept study suggests the feasibility of
      utilizing MVPs for predictive size-based viral clearance assessments during
      process development and characterization as an alternative to homologous
      infectious virus.

PMID- 30194918
TI  - Cannabidiol skews biased agonism at cannabinoid CB1 and CB2 receptors with
      smaller effect in CB1-CB2 heteroreceptor complexes.
AB  - Currently, biased agonism is at the center stage of drug development approaches.
      We analyzed effects of a battery of cannabinoids plus/minus cannabidiol (CBD) in
      four functional parameters (cAMP levels, phosphorylation of extracellular signal
      regulated kinases (ERK1/2), beta-arrestin recruitment and label-free/DMR) in HEK
      293T cells expressing cannabinoid receptors, CB1 or CB2, or CB1-CB2
      heteroreceptor complexes. In all cases two natural agonists plus two selective
      synthetic agonists were used. Furthermore, the effect of cannabidiol, at a dose
      (100 nM) that does not allow significant binding to the orthosteric center of
      either receptor, was measured. From the huge amount of generated data, we would
      like to highlight that the two psychotropic molecules (Delta9
      tetrahydrocannabinol/THC and CP-55940) showed similar bias in CB1R and that the
      bias of THC was particularly relevant toward MAPK pathway. Furthermore, THC did
      not activate the Gi protein coupled to CB2R. Interestingly, the biased agonism
      was reduced when assays were performed in cells expressing the two receptors,
      thus suggesting that the heteromer allows less functional selectivity. In terms
      of cannabidiol action, the phytocannabinoid altered the functional responses,
      likely by allosteric means, and modified potency, agonist IC50/EC50 values and
      biased agonism in qualitative and/or quantitative different ways depending on the
      agonist. The effect of cannabidiol on anandamide actions on both cannabinoid
      receptors was particularly noteworthy as was significantly different from that of
      other compounds. Results are a compendium of data on biased agonism on
      cannabinoid receptors in the absence and presence of cannabidiol. In addition,
      for the first time, GPCR biased agonism is characterized in an heteromeric
      context.

PMID- 30194919
TI  - Lung morphogenesis is orchestrated through Grainyhead-like 2 (Grhl2)
      transcriptional programs.
AB  - The highly conserved transcription factor Grainyhead-like 2 (Grhl2) exhibits a
      dynamic expression pattern in lung epithelium throughout embryonic development.
      Using a conditional gene targeting approach to delete Grhl2 in the developing
      lung epithelium, our results demonstrate that Grhl2 plays multiple roles in lung
      morphogenesis that are essential for respiratory function. Loss of Grhl2 leads to
      impaired ciliated cell differentiation and perturbed formation of terminal
      saccules. Critically, a substantial increase in Sox9-positive distal tip
      progenitor cells was observed following loss of Grhl2, suggesting that Grhl2
      plays an important role in branching morphogenesis. Gene transcription profiling
      of Grhl2-deficient lung epithelial cells revealed a significant down regulation
      of Elf5, a member of the Ets family of transcription factors. Furthermore, ChIP
      and comparative genomic analyzes confirmed that Elf5 is a direct transcriptional
      target of Grhl2. Taken together, these results support the hypothesis that Grhl2
      controls normal lung morphogenesis by tightly regulating the activity of distal
      tip progenitor cells.

PMID- 30194920
TI  - Transient receptor potential vanilloid 1-6 (Trpv1-6) gene expression in the mouse
      brain during estrous cycle.
AB  - In recent years estradiol has emerged as a potential regulator of transient
      receptor potential vanilloid (TRPV) cationic channels in the peripheral tissues
      and sensory neurons, however, its analogous role in the CNS is poorly understood.
      TRPV channels modulate Ca2+ signalling, neurotransmission and behaviour, and
      expression of these ion channels and estrogen receptors show a great degree of
      overlap in different brain regions. Herein, we probe if Trpv1-6 genes contain
      estrogen receptor-binding sites and if their expression in different brain
      regions is modulated during estrous cycle. Bioinformatics analysis of the mouse
      Trpv1-6 gene sequences showed presence of putative functional estrogen response
      element in their promoter regions. Using qRT-PCR, Trpv1-6 mRNA expression was
      observed in the olfactory bulb, cortex, hypothalamus, hippocampus, brainstem, and
      cerebellum of mouse. In these regions, compared to estrus, metestrus, and
      diestrus, reduced levels of Trpv1 and Trpv5 but elevated Trpv2 and Trpv6 mRNA
      levels were observed during proestrus. Lower levels of Trpv3 and Trpv4 mRNAs were
      seen during estrus but higher expression of Trpv3 during metestrus and diestrus,
      and Trpv4 during proestrus was observed. Estradiol seems to regulate Trpv1/Trpv5
      and Trpv2/Trpv6 mRNA expression in opposite manner. Except Trpv4 mRNA expression
      in the hippocampus and Trpv6 expression in the olfactory bulb, hippocampus and
      brainstem, expression of other members of TRPV subfamily in distinct brain
      regions of male mice was comparable to those in metestrus and diestrus mice. We
      suggest that the circulating levels of estradiol during the estrous cycle may
      differentially regulate the activity of TRPV1-6 ion channels in the brain.

PMID- 30194921
TI  - Morphology of immature blow fly Hypopygiopsis infumata (Bigot) (Diptera:
      Calliphoridae), a potential species of forensic importance.
AB  - Blow flies of the genus Hypopygiopsis are forensically-important, as their larvae
      are commonly associated with human corpses. Within a forensic entomology context,
      species identification of specimens collected from human corpses is the initial
      mandatory step in the investigation. Without identification, complete
      interpretation of entomological evidence is challenged. In this study, the
      ultrastructures of eggs, all instars, and puparia of Hypopygiopsis infumata
      (Bigot) are presented based on assessment with scanning electron microscopy (SEM)
      and light microscopy (LM). Distinctive features used for species identification
      of all stages are highlighted. Eggs have a slightly widening median area
      extending almost the entire length. Larvae are vermiform-shaped, creamy white,
      and have a smooth integument. The pseudocephalon of larvae bears sensory
      structures (i.e., antennal dome, maxillary palpus and ventral organ). In the
      first instar, two tufts of cirri are observed along the dorsal margin of the
      mouth opening. In the second and third instars, six minute tubercles are present
      along the peripheral rims of the last abdominal segment. The anterior spiracle of
      the second, third instar, and puparia is fan-shape of single row, comprising 9-11
      papillae. The cuticular spines between the 1st and 2nd thoracic segments of the
      third instar possess many rows of posteriorly-projecting acuminate spines in
      clusters. In puparia, at the latero-dorsal edge of the 1st abdominal segment, a
      cluster of ~92 bubble membranes is present in young puparia (20-24 h). The
      peristigmatic tufts adjacent to the posterior spiracle of the second instar,
      third instar, and puparia are heavily branches of long, fine hairs. Our results
      demonstrate the morphology of eggs, larvae, and puparia of H. infumata are
      similar to other species in Hypopygiopsis. This study highlighted the main
      features of cephaloskeleton of H. infumata larvae as observed under LM.
      Particular attention is given to oral sclerite and rough surface of dorsal cornua
      which can distinguish between H. infumata and H. tumrasvini.

PMID- 30194922
TI  - The role of gamma delta T lymphocytes in breast cancer: a review.
AB  - Gammadelta T (gammadeltaT) lymphocytes have provoked interest in oncology,
      particularly as regards their potential use in immunotherapy, because of their
      unique ability to recognise antigens without a requirement for major
      histocompatibility complex antigen presentation, and to quickly activate an anti
      tumour response. However, work in some cancers has suggested that they also have
      pro-tumourigenic activity. Their role in breast cancer is unclear. This review
      outlines the evidence to date in in vitro studies, in vivo mouse models and in
      human studies regarding the role of gammadeltaT lymphocytes in breast cancer. We
      describe the seemingly opposing roles of the predominantly circulating
      Vgamma9Vdelta2+ subtype, which can suppress tumour growth through direct
      cytotoxicity, induction of apoptosis and inhibition of angiogenesis, and the
      predominantly tumour-infiltrating gammadelta1+ subtype which can promote tumour
      growth and spread through immunosuppressant effects. We summarise the evidence in
      breast cancer for the mechanisms of action of gammadeltaT lymphocytes and
      describe how factors in the tumour microenvironment may affect their function,
      polarising them towards a pro-tumourigenic, immune-suppressing role. We also
      describe the experience to date of gammadeltaT lymphocytes in immunotherapy for
      breast cancer and suggest the direction of work going forward, particularly as
      regards different breast cancer subtypes.

PMID- 30194924
TI  - A Literature Review of Midwifery-Led Care in Reducing Labor and Birth
      Interventions.
AB  - Certified nurse-midwives are usually recognized as independently practicing
      advanced practice registered nurses because they provide maternity care to
      pregnant women in various states. In the United States, certified nurse-midwives
      are historically underused. Culture favors physician-led care, with 90% of all
      births attended by physicians. Midwifery-led care is considered high-touch/low
      intervention and is guided by a philosophy of care that regards pregnancy and
      childbirth as normal life events for most women. Evidence from the literature
      supports midwifery-led care as being safe, effective, and associated with fewer
      interventions.

PMID- 30194925
TI  - Protein probes to visualize sphingomyelin and ceramide phosphoethanolamine.
AB  - Sphingomyelin (SM) is a major sphingolipid in mammalian cells whereas its analog,
      ceramide phosphoethanolamine (CPE) is found in trace amounts in mammalian cells
      and in larger amounts in invertebrates such as insect cells like Drosophila
      melanogaster. To visualize endogenous SM or CPE, we need specific probes able to
      recognize the chemical structure of the lipid, rather than its physical property.
      A limited number of proteins is known to specifically and strongly bind SM or
      CPE. These proteins are either toxins produced by non-mammalian organisms,
      subunits or fragments of toxins or a protein that has similar structure to a
      toxin. These proteins labeled with small fluorophore (e.g. Alexa Fluor) or
      conjugated to fluorescent proteins (e.g. mCherry) or other types of markers (e.g.
      125I, maltose-binding protein) are used to detect SM or CPE. Here we summarize
      the characteristics of specific SM-binding proteins, lysenin and equinatoxin II;
      CPE- and SM/cholesterol (Chol) binding aegerolysin proteins, pleurotolysin A2,
      ostreolysin and erylysin A and SM/Chol-binding protein, nakanori. Then we give
      examples of their applications including their limitations related not only to
      their lipid specificity and binding constants, but also to the lipid organization
      in the membrane.

PMID- 30194927
TI  - Medicaid and receipt of interval postpartum long-acting reversible contraception.
AB  - OBJECTIVE: We sought to evaluate the impact of insurance type on receipt of an
      interval postpartum LARC, controlling for demographic and clinical factors. STUDY
      DESIGN: This is a retrospective cohort study of 1072 women with a documented plan
      of LARC for contraception at time of postpartum discharge. This is a secondary
      analysis of 8654 women who delivered at 20 weeks or beyond from January 1, 2012,
      through December 31, 2014, at an urban teaching hospital in Ohio. LARC receipt
      within 90 days of delivery, time to receipt, and rate of subsequent pregnancy
      after non-receipt were compared between women with Medicaid and women with
      private insurance. Postplacental LARC was not available at the time of study
      completion. RESULTS: One hundred eighty-seven of 822 Medicaid-insured and 43 of
      131 privately insured women received a LARC postpartum (22.7% vs 32.8%, P=.02).
      In multivariable analysis, private insurance status was not significantly
      associated with LARC receipt (OR 1.29, 95% C.I. 0.83-1.99) though adequate
      prenatal care was (OR 2.33, 95% C.I. 1.42-4.00). Of women who wanted but did not
      receive a LARC, 208 of 635 (32.8%) Medicaid patients and 19 of 88 (21.6%)
      privately insured patients became pregnant within 1 year (P=.02). CONCLUSION:
      Differences in receipt of interval postpartum LARC were not significant between
      women with Medicaid insurance versus private insurance after adjusting for
      clinical and demographic factors. Adequate prenatal care was associated with LARC
      receipt. Medicaid patients who did not receive a LARC were more likely to become
      pregnant within one year of delivery than those with private insurance.
      IMPLICATIONS: While insurance-related barriers have been reduced given recent
      policy changes, access to care remains an important determinant of postpartum
      LARC provision and subsequent unintended pregnancy.

PMID- 30194928
TI  - In Vivo Confocal Microscopy Shows Alterations in Nerve Density and Dendritiform
      Cell Density in Fuchs' Endothelial Corneal Dystrophy.
AB  - PURPOSE: To evaluate corneal nerve and immune cell alterations in Fuchs'
      endothelial corneal dystrophy (FECD) and pseudophakic bullous keratopathy (PBK)
      by laser in vivo confocal microscopy (IVCM) as correlated to corneal sensation
      and endothelial cell loss. DESIGN: Prospective, cross-sectional, controlled
      study. METHODS: Thirty-three eyes with FECD were compared to 13 eyes with PBK and
      17 normal age-matched control eyes at a tertiary referral center. FECD was
      classified into early (without edema) and late stage (with edema). Corneal IVCM
      and esthesiometry were performed. Corneal nerve and immune dendritiform cell (DC)
      alterations were evaluated and correlated to clinical parameters. RESULTS: FECD
      and PBK eyes showed significantly (P = .001) diminished total nerve length (11.5
      +/- 1.3 and 2.9 +/- 0.7 mm/mm2) and number (8.8 +/- 1.1 and 2.2 +/- 0.4 n/frame),
      compared to controls (23.3 +/- 8.1 mm/mm2 and 25.9 +/- 1.3 n/frame). Decreased
      nerves corresponded to diminished sensation in FECD (4.9 +/- 0.2 cm; R = 0.32; P
      = .045), compared to controls (5.9 +/- 0.04 cm). Early- and late-stage FECD
      showed significantly reduced total nerve length (13.1 +/- 1.4 and 9.9 +/- 1.2
      mm/mm2, respectively) and number (8.2 +/- 2.5 and 6.5 +/- 2.1 n/frame), compared
      to controls (P < .001). DC density was significantly increased in FECD (57.8 +/-
      10.4 cells/mm2; P = .01), but not in PBK (47.7 +/- 11.6 cells/mm2; P = .60)
      compared to controls (22.5 +/- 4.5 cells/mm2). A subset of early FECD patients
      (7/22) demonstrated very high DC density (>100/mm2). CONCLUSION: IVCM
      demonstrates profound diminishment of subbasal corneal nerves in early- and late
      stage FECD and in PBK, correlating to decreased sensation. Increased DC density
      in early FECD demonstrates potential subclinical inflammation. The data suggest
      that reduction in subbasal nerves and increased immune activation may play a role
      in the pathophysiology of FECD.

PMID- 30194930
TI  - Outcome and Prognostic Factors of Phacoemulsification Cataract Surgery in Vogt
      Koyanagi-Harada Uveitis.
AB  - PURPOSE: To investigate visual outcome and prognostic factors following cataract
      surgery in patients with Vogt-Koyanagi-Harada (VKH) disease. DESIGN:
      Retrospective, interventional case series. METHODS: The history, clinical
      characteristics, best-corrected visual acuity (BCVA), full-field
      electroretinogram (ERG), intraocular inflammation, complications, and extraocular
      manifestations were analyzed retrospectively. RESULTS: One hundred and forty
      eight male (214 eyes) and 138 female (194 eyes) VKH patients with complicated
      cataract were included. Surgery was performed on 352 eyes after complete control
      of intraocular inflammation for at least 3 months. In another set of 56 eyes,
      surgery was done 1 month after intraocular inflammation control. There was no
      difference in postoperative complications or BCVA between these 2 groups. The
      main complications after surgery were hyphema, ocular hypertension, and moderate
      anterior chamber reaction. Average preoperative visual acuity was 0.08. At last
      visit, BCVA was improved in 405 eyes (99.3%). The preoperative BCVA, treatment
      delay after disease onset, preoperative intraocular hypertension, and iris
      synechiae were associated with final visual outcome. Other parameters such as
      postoperative inflammation, IOL type, and presence of extraocular VKH features
      did not affect final BCVA. Poor visual acuity was caused by optic nerve atrophy,
      choroidoretinal neovascularization, and subretinal fibrosis. Poor postoperative
      BCVA was associated with an abnormal preoperative ERG profile. CONCLUSIONS:
      Phacoemulsification and IOL implantation in VKH patients can be safely and
      successfully performed in quiet eyes even after 1 month following the last signs
      of inflammation. Visual prognosis was associated with preoperative BCVA,
      treatment delay after disease onset, preoperative intraocular hypertension, iris
      synechiae, and presence of preoperative ERG abnormalities.

PMID- 30194929
TI  - A Long-term Safety Study of Latanoprost in Pediatric Patients With Glaucoma and
      Ocular Hypertension: A Prospective Cohort Study.
AB  - PURPOSE: The objective was to assess the long-term effect of treatment with
      latanoprost on ocular development and safety in pediatric patients with glaucoma
      and ocular hypertension. DESIGN: Prospective cohort study. METHODS: This was a
      prospective 3-year cohort study conducted in 14 countries in Europe and South
      America. Patients aged < 18 years with glaucoma or ocular hypertension were
      enrolled into either the latanoprost or non-prostaglandin (non-PG) group in this
      observational study. The primary endpoint was change in best-corrected visual
      acuity (BCVA) from baseline to 3 years. Several secondary endpoints were
      evaluated, including corneal thickness and ocular hyperpigmentation. For
      treatment comparison, analysis of covariance (ANCOVA) was used for continuous
      endpoints and Fisher exact test was applied for proportion of participants with
      clinically significant deterioration events. RESULTS: A total of 175 patients
      were enrolled: 102 in the latanoprost group (median follow-up: 36.7 months) and
      73 in the non-PG group (median follow-up: 36.1 months). There was no
      statistically significant difference between the latanoprost and the non-PG
      groups (aged 5 to <18 years) in BCVA change from baseline (least square mean
      logMAR difference -0.03 [95% confidence interval: -0.12, 0.06]), corneal
      thickness, or ocular hyperpigmentation. CONCLUSIONS: Latanoprost had an
      acceptable safety profile with no evidence of inducing clinically meaningful or
      statistically significant changes in ocular development or ocular
      hyperpigmentation in pediatric patients with glaucoma and ocular hypertension.

PMID- 30194931
TI  - The Blunt End: Surgical Challenges of Gene Therapy for Inherited Retinal
      Diseases.
AB  - PURPOSE: To review barriers to effective transduction of cells in the subretinal
      plane during gene therapy surgery for inherited retinal dystrophies (IRD).
      DESIGN: Perspective. METHODS: Case-based learning in clinical trials and
      commercial applications of gene therapy in a tertiary care, university-affiliated
      hospital. MEDLINE search for publications relevant to retinal surgical technique
      for gene therapy, clinical trials results for gene therapy of IRD, adenoviral
      associated viral vector design, and immune response to viral vectors. RESULTS:
      The most important surgical issues are safe access to the subretinal space,
      intraoperative visualization with optical coherence tomography to protect the
      macula, and quantitation of viral dose. Other issues for retinal surgeons are
      patient selection, target zone planning, and control of inflammation. Vector
      related issues that may affect the precision of treatment involve capsid
      interaction with the innate and adaptive immune systems and selective targeting
      of cell types. CONCLUSIONS: Most current gene therapy vectors for monogenic IRD
      require physical proximity to target tissues under the retina in order to work.
      New surgical skills and new instrumentation are under development. So far, the
      host immune response does not seem to cause rejection of genes delivered by viral
      vectors but the efficiency of transduction can only be indirectly assessed by
      long-term visual outcomes.

PMID- 30194932
TI  - Persistently elevated plasma heart-type fatty acid binding protein concentration
      is related with poor outcome in acute decompensated heart failure patients.
AB  - BACKGROUND: The aim of the study was to determine clinical and prognostic role of
      repeated heart-type fatty acid binding protein (hFABP) measurements in acute
      decompensated HF (ADHF) patients. METHODS: In seventy-seven ADHF patients (III
      and IV NYHA class, mean age 70 +/- 12.7 years, mean left ventricle ejection
      fraction [LVEF] 29.73 +/- 13.3%) plasma hFABPs concentrations (SunRed Biological
      Technology) were measured twice - on admission and at discharge (mean time of
      hospitalization 10.7 +/- 4.9 days). Combined end point (CEP), assessed after mean
      9.2 +/- 7.3 months, was defined as death or the need of HF re-hospitalization.
      RESULTS: Median hFABP concentration on admission was significantly lower than at
      discharge. hFABP concentrations on admission significantly correlated with
      echocardiographic parameters of LV remodeling. Among fifty-six patients (72.7%)
      who reached CEP, significantly higher admission and discharge hFABP
      concentrations were found. Patients with plasma discharge hFABP concentrations
      higher than 7.8 ng/mL were at higher risk of CEP (log-rank test, p = 0.01).
      Logistic stepwise regression analysis revealed discharge hFABP, LVEF and left
      ventricle mass index independent and significant predictors of CEP (p < 0.05).
      CONCLUSIONS: In ADHF patients plasma hFABP admission concentrations are related
      with LV remodeling. Persistently elevated hFABP concentrations have prognostic
      value, as may reflect continuous myocardial damage despite effective treatment
      and clinical improvement.

PMID- 30194933
TI  - The potential of exosomes derived from colorectal cancer as a biomarker.
AB  - Colorectal cancer (CRC) is one of the most frequent causes of cancer death. The
      diagnosis and treatment for metastatic CRC and patients with drug resistance
      remains poor. Cancer cells characteristically produce and release exosomes, which
      act as a new signal pattern in the occurrence and development of tumors.
      Circulating exosomes constitute promising biomarkers for early diagnosis of
      cancer patients. However, the potential of exosomes for clinical biomarker is
      hampered by their variousness and multi-sources. To this aim, we set out to solve
      the problem of discrimination and classification of exosomes. The cell culture
      supernatants of CRC cells, renal cell carcinoma cells and breast cancer cells
      were used for isolating exosomes. Then characteristic exosomal tumor markers were
      explored by Roche Cobas E601 fully automated electrochemiluminescence immunoassay
      systems, western blot and flow cytometry analysis. The results showed that CK19
      was commonly expressed in exosomes derived from colorectal cells, TAG72 was
      mainly expressed in exosomes of 5-FU-resistant CRC cells and CA125 in those of
      high metastatic CRC cells. In addition, tumor interstitial fluid derived exosomes
      and patients' plasma derived exosomes showed different levels of CK19, TAG72 and
      CA125. Collectively, these data indicated that exosomes derived CK19 is
      correlated with colorectal tissue. TAG72-rich exosomes indicate that CRC patients
      might be resistant to 5-Fluorouraci. CA125-rich exosomes might be as metastatic
      CRC markers. These provide a good prospect for cell exosomes as novel, non
      invasive clinical tool for diagnosing CRC and predicting its progression.

PMID- 30194934
TI  - Immunoluminometric assay for copeptin measurement in cerebrospinal fluid:
      Technical aspects and pilot study.
AB  - BACKGROUND: Copeptin acts as surrogate marker under stress stimuli, as well as an
      outcome predictor based on serum or plasma concentration in patients suffering
      intracranial hemorrhage, aneurysmal subarachnoid hemorrhage (aSAH), and stroke.
      The aim of this study was to establish a method for quantification of copeptin
      levels in cerebrospinal fluid (CSF) and to demonstrate its clinical applicability
      in patients following aSAH. METHODS: This assay was validated for CSF samples
      using a commercial immunoluminometric assay (IMLA). For the control group (10
      patients), CSF copeptin levels were determined in patients without signs of acute
      neurological diseases and who underwent a diagnostic lumbar puncture. The pilot
      cohort included calculation of copeptin levels in CSF and in serum of patients
      following aSAH. RESULTS: The control group had CSF copeptin levels lower than
      0.78 pmol/L-1. Among patients with aSAH, CSF copeptin values had a mean of 20.1
      pmol/L-1 and serum copeptin concentrations had a mean of 61.39 pmol/L-1.
      CONCLUSIONS: This assay provides to best of our knowledge for the first time
      initial ranges values of CSF copeptin for patients without acute neurological
      disease and in patients with aSAH. Thus, it opens new doors to develop further
      calculations and relationships between diseases biomarker and outcome prediction.

PMID- 30194935
TI  - RAS mutations in acute myeloid leukaemia patients: A review and meta-analysis.
AB  - RAS oncogene mutations frequently occur in acute myeloid leukaemia (AML), but the
      prognostic significance of RAS mutations in AML is inconclusive. We searched the
      databases of PubMed, Web of Science, EMBASE, and Cochrane from 1990 to 2018. In
      this study, 24 eligible studies were included, and the meta-analysis was
      conducted with the Comprehensive Meta-Analysis Version 2 software program. The
      row hazard ratio (HR) was adjusted and re-evaluated when publication bias existed
      after detecting all the heterogeneities. A combined analysis showed that RAS
      mutations were not associated with a poor prognosis in general AML patients (HR:
      0.96, 95% CI: 0.78-1.19, p = 0.70). To further verify the results, a subgroup
      analysis was conducted. Interestingly, in the analysis of age bracket, children
      with RAS mutations had an unfavourable survival (HR: 1.35, 95% CI: 1.05-1.75, p =
      0.02) of AML, but the adults did not (HR: 0.87, 95% CI: 0.70-1.09, p = 0.21).
      Further analysis of the subgroup of children indicated that patients with NRAS
      mutations had an adverse prognosis (HR: 1.55, 95% CI: 1.13-2.12, p = 0.007), but
      not those with KRAS mutations (HR: 1.51, 95% CI: 0.34-6.73, p = 0.59). In
      conclusion, this study revealed that RAS mutations did not influence the over
      survival for adults with AML. However, NRAS mutations may be a key prognostic
      marker related with poor survival for children with AML.

PMID- 30194936
TI  - Sparstolonin B (SsnB) attenuates liver fibrosis via a parallel conjugate pathway
      involving P53-P21 axis, TGF-beta signaling and focal adhesion that is TLR4
      dependent.
AB  - SsnB previously showed a promising role to lessen liver inflammation observed in
      a mouse model of NAFLD. Since NAFLD can progress to fibrosis, studies were
      designed to unravel its role in attenuating NAFLD associated fibrosis. Using both
      in vivo and in vitro approaches, the study probed the possible mechanisms that
      underlined the role of SsnB in mitigating fibrosis. Mechanistically, SsnB, a TLR4
      antagonist, decreased TLR4-PI3k akt signaling by upregulating PTEN protein
      expression. It also decreased MDM2 protein activation and increased p53 and p21
      gene and protein expression. SsnB also downregulated pro-fibrogenic hedgehog
      signaling pathway, inhibited hepatic stellate cell proliferation and induced
      apoptosis in hepatic stellate cells, a mechanism that was LPS dependent. Further,
      SsnB decreased fibrosis by antagonizing TLR4 induced TGFbeta signaling pathway.
      Alternatively, SsnB augmented BAMBI (a TGFbeta pseudo-receptor) expression in
      mice liver by inhibiting TLR4 signaling pathway and thus reduced TGFbeta
      signaling, resulting in decreased hepatic stellate cell activation and
      extracellular matrix deposition. In vitro experiments on human hepatic stellate
      cell line showed that SsnB increased gene and protein expression of BAMBI. It
      also decreased nuclear co-localization of phospho SMAD2/3 and SMAD4 protein and
      thus attenuated TGFbeta signaling in vitro. We also observed a significant
      decrease in phosphorylation of SMAD2/3 protein, decreased STAT3 activation,
      alteration of focal adhesion protein and stress fiber disassembly upon SsnB
      administration in hepatic stellate cells which further confirmed the antagonistic
      effect of SsnB on TLR4-induced fibrogenesis.

PMID- 30194926
TI  - Sphingolipids and lipid rafts: Novel concepts and methods of analysis.
AB  - About twenty years ago, the functional lipid raft model of the plasma membrane
      was published. It took into account decades of research showing that cellular
      membranes are not just homogenous mixtures of lipids and proteins. Lateral
      anisotropy leads to assembly of membrane domains with specific lipid and protein
      composition regulating vesicular traffic, cell polarity, and cell signaling
      pathways in a plethora of biological processes. However, what appeared to be a
      clearly defined entity of clustered raft lipids and proteins became increasingly
      fluid over the years, and many of the fundamental questions about biogenesis and
      structure of lipid rafts remained unanswered. Experimental obstacles in
      visualizing lipids and their interactions hampered progress in understanding just
      how big rafts are, where and when they are formed, and with which proteins raft
      lipids interact. In recent years, we have begun to answer some of these questions
      and sphingolipids may take center stage in re-defining the meaning and functional
      significance of lipid rafts. In addition to the archetypical cholesterol
      sphingomyelin raft with liquid ordered (Lo) phase and the liquid-disordered (Ld)
      non-raft regions of cellular membranes, a third type of microdomains termed
      ceramide-rich platforms (CRPs) with gel-like structure has been identified. CRPs
      are "ceramide rafts" that may offer some fresh view on the membrane mesostructure
      and answer several critical questions for our understanding of lipid rafts.

PMID- 30194937
TI  - Pharmacological characterization of the orexin/hypocretin receptor agonist Nag
      26.
AB  - One promising series of small-molecule orexin receptor agonists has been
      described, but the molecular pharmacological properties, i.e. ability and potency
      to activate the different orexin receptor-regulated signal pathways have not been
      reported for any of these ligands. We have thus here assessed these properties
      for the most potent ligand of the series, 4'-methoxy-N,N-dimethyl-3'-[N-(3-{[2-(3
      methylbenzamido)ethyl]amino}phenyl sulfamoyl]-(1,1'-biphenyl)-3-carboxamide (Nag
      26). Chinese hamster ovary-K1 cells expressing human orexin receptor subtypes OX1
      and OX2 were used. Ca2+ elevation and cell viability and death were assessed by
      fluorescent methods, the extracellular signal-regulated kinase pathway by a
      luminescent Elk-1 reporter assay, and phospholipase C and adenylyl cyclase
      activities by radioactive methods. The data suggest that for the Gq-dependent
      responses, Ca2+, phospholipase C and Elk-1, Nag 26 is a full agonist for both
      receptors, though of much lower potency. However, saturation was not always
      reached for OX1, partially due to Nag 26's low solubility and partially because
      the response decreased at high concentrations. The latter occurs in the same
      range as some reduction of cell viability, which is independent of orexin
      receptors. Based on the EC50, Nag 26 was OX2-selective by 20-200 fold in
      different assays, with some indication of biased agonism (as compared to orexin
      A). Nag 26 is a potent orexin receptor agonist with a largely similar
      pharmacological profile as orexin-A. However, its weaker potency (low-mid
      micromolar) and low water solubility as well as the non-specific effect in the
      mid-micromolar range may limit its usefulness under physiological conditions.

PMID- 30194938
TI  - Modulation of tetrodotoxin-resistant Na+ channels by amitriptyline in dural
      afferent neurons.
AB  - Migraine is characterized by recurrent and disabling headaches; therefore,
      several drugs have been widely prescribed to prevent acute migraine attacks.
      Amitriptyline, a tricyclic antidepressant, is among the most commonly
      administered. It is poorly known, however, whether amitriptyline modulates the
      excitability of dural afferent neurons that transmit pain signals from the dura
      mater. In this study, the effects of amitriptyline on tetrodotoxin-resistant (TTX
      R) Na+ channels were examined in acutely isolated rat dural afferent neurons,
      which were identified by the fluorescent dye DiI. The TTX-R Na+ currents (INa)
      were recorded from medium-sized DiI-positive neurons using a whole-cell patch
      clamp technique. Amitriptyline (3 MUM) slightly reduced the peak component of
      transient INa and induced a marked decrease in the steady-state component of
      transient TTX-R INa, as well as in the slow ramp-induced TTX-R INa. Our findings
      suggest that amitriptyline specifically inhibits persistent Na+ currents mediated
      by TTX-R Na+ channels. While amitriptyline had minor effects on voltage
      activation/inactivation, it increased the extent of the use-dependent inhibition
      of TTX-R Na+ channels. Amitriptyline also affected the inactivation kinetics of
      TTX-R Na+ channels by significantly accelerating the inactivation of TTX-R Na+
      channels and slowing the subsequent recovery. Amitriptyline decreased the number
      of action potentials by increasing the threshold for their generation. In
      conclusion, the amitriptyline-mediated diverse modulation of TTX-R Na+ channels
      would be, at least in part, responsible for its prophylactic efficacy for
      migraine attacks.

PMID- 30194939
TI  - Epigallocatechin-3-gallate and BIX-01294 have different impact on epigenetics and
      senescence modulation in acute and chronic myeloid leukemia cells.
AB  - Myeloid leukemia treatment is quite successful nowadays; nevertheless the
      development of new therapies is still necessary. In the present study, we
      investigated the potential of epigenetic modulators EGCG (epigallocatechin-3
      gallate) and BIX-01294 (N-(1-benzylpiperidin-4-yl)-6,7-dimethoxy-2-(4-methyl-1,4
      diazepan-1-yl)quinazolin-4-amine) to alter epigenetic state and cause cellular
      senescence in acute and chronic myeloid leukemia NB4 and K562 cells. We have
      shown that after leukemia cell treatment with EGCG and BIX-01294 the
      proliferation and survival were inhibited of both cell lines; however, only NB4
      cells underwent apoptosis. Both epigenetic modulators caused cell cycle arrest in
      G0/G1 phase as assessed by RT-qPCR (p53, p21, Rb) and flow cytometry analysis.
      Increased levels of ATM, HMGA2, phosphorylated ATM, and SA-beta-galactosidase
      staining indicated that EGCG caused cellular senescence, whereas BIX-01294 did
      not. Immunoblot analysis of epigenetic players DNMT1, HP1alpha, H3K9me3, EZH2,
      and SUZ12 demonstrated beneficial epigenetic modulation by both agents with
      exception of mainly no epigenetic changes caused in K562 cells by EGCG.
      Therefore, we suggest EGCG as a promising epigenetic modulator for acute
      promyelocytic leukemia therapy and as a potential cellular senescence inducer in
      both acute and chronic myeloid leukemia treatment, whereas BIX-01294 could be
      beneficial as an epigenetic modifier for both myeloid leukemias treatment.

PMID- 30194940
TI  - alpha1A-Adrenoceptors, but not alpha1B- or alpha1D-adrenoceptors, contribute to
      enhanced contractile response to phenylephrine in cooling conditions in the rat
      tail artery.
AB  - Cutaneous arteries show enhanced contraction in response to cooling, which is
      suggested to be mediated via alpha2C-adrenoceptors. We have previously shown that
      alpha1-adrenoceptors are also involved in the enhanced contraction in cooling
      conditions. In the present study, we aimed to identify the alpha1-adrenoceptor
      subtype involved in the response. Phenylephrine-induced contraction was enhanced
      by cooling to 24  degrees C in isolated rat tail arteries but suppressed in iliac
      arteries and aorta. At 37  degrees C, RS100329 (3 nM), an alpha1A-adrenoceptor
      antagonist, shifted the concentration-response curve of phenylephrine to the
      right in tail and iliac arteries, but not in aorta, while BMY7378 (10 nM), an
      alpha1D-adrenoceptor antagonist, shifted them to the right in aorta and iliac
      arteries, but not in tail arteries. At 24  degrees C, RS100329 (3 nM) shifted the
      concentration-response curve of phenylephrine to the right and decreased the
      maximum contraction in tail arteries. The inhibitory effects of RS100329 (3 nM)
      were more pronounced at 24  degrees C, compared to at 37  degrees C, implying
      larger contribution of alpha1A-adrenoceptors at 24  degrees C. In tail arteries,
      the maximum contraction of A-61603, an alpha1A-adrenoceptor agonist, was larger
      at 24  degrees C than at 37  degrees C. In contrast, in iliac arteries, the
      maximum contraction of A-61603 was smaller and its EC50 was smaller at 24 
      degrees C than at 37  degrees C. Under the condition where alpha1D-adrenoceptors
      were blocked, phenylephrine-induced contraction of iliac arteries was rather
      enhanced by cooling to 24  degrees C. These results suggest that alpha1A
      adrenoceptors contribute to the enhanced contraction of cutaneous arteries in
      cooling conditions.

PMID- 30194941
TI  - Antioxidant N-acetylcysteine inhibits maladaptive myocyte autophagy in pressure
      overload induced cardiac remodeling in rats.
AB  - Increased oxidative stress and myocyte autophagy co-exist in cardiac remodeling.
      However, it is unclear whether oxidative stress mediates maladaptive myocyte
      autophagy in pathological ventricular remodeling. In this study, we tested the
      hypothesis that antioxidants prevent maladaptive myocyte autophagy in pressure
      overload-induced left ventricular (LV) remodeling. Sprague-Dawley rats underwent
      abdominal aortic constriction (AAC) or sham operation. The animals were
      randomized to receive an antioxidant N-acetylcysteine (NAC), an autophagy
      inhibitor 3-methyladenine (3-MA) or placebo treatment for 2 weeks. We measured LV
      structure and function by echocardiography and hemodynamics, myocyte autophagy
      and oxidative stress assessed by 8-hydroxy-2-deoxyguanosine (8-OHdG). AAC rats
      exhibited increased LV hypertrophy assessed by LV wall thickness and myocyte
      cross-sectional area. NAC prevented LV hypertrophy in AAC rats. There were no
      significant differences in LV fractional shortening, end-diastolic dimension and
      the maximal rate of LV pressure rise among the groups. AAC rats showed an
      increase in myocardial 8-OHdG that was prevented by NAC. The expression of LC3 II
      protein, a marker of autophagy, was increased at 2 weeks after AAC.
      Immunohistochemical scores further confirmed the increase in LC3 expression in
      AAC rats. The expression of autophagic proteins Beclin1 and Atg12 and ERK
      activity were also increased in AAC rats. NAC prevented the increases in LC3 II
      protein, LC3 scores, Beclin1, Atg12 and ERK activity in AAC rats. Inhibition of
      autophagy by 3-MA prevented LV hypertrophy after pressure overload. These
      findings suggest that antioxidants may be of value to prevent pressure overload
      induced cardiac remodeling through inhibition of maladaptive myocyte autophagy.

PMID- 30194942
TI  - Dihydromyricetin from ampelopsis grossedentata protects against vascular
      neointimal formation via induction of TR3.
AB  - Vine tea has been used as a medicinal herb in traditional Chinese medicine for
      hundreds of years. As the most abundant ingredient in vine tea, Dihydromyricetin
      (DHM) has been reported to exert anti-inflammatory, antioxidant, and anti
      cardiovascular disease. However, the role of DHM in injury-induced neointimal
      formation remains poorly characterized. We determined the effects of DHM on
      ligation-induced carotid artery neointimal formation. We found that ligation
      induced carotid artery neointimal formation could be significantly attenuated by
      DHM treatment. We provide evidence that DHM increases orphan nuclear receptor TR3
      expression in smooth muscle cell (SMC) and carotid artery. Moreover,
      overexpression and loss-of-function strategies of TR3 were done to overexpression
      and knockdown of TR3, and demonstrate that DHM promotes SMC differentiation,
      however, inhibits SMC proliferation and migration, via regulating expression of
      TR3. Collectively, we reveal that DHM may be a therapeutic agent for the
      treatment of injury-induced vascular diseases.

PMID- 30194943
TI  - Diagnostic and therapeutic neuroradiology of neurodegenerative diseases.

PMID- 30194944
TI  - Antimicrobial resistance plasmid reservoir in food and food-producing animals.
AB  - Antimicrobial resistance (AMR) plasmids have been recognized as important vectors
      for efficient spread of AMR phenotypes. The food reservoir includes both food
      producing animals and food products, and a huge diversity of AMR plasmids have
      been reported in this sector. Based on molecular typing methods and/or whole
      genome sequencing approaches, certain AMR genes/plasmids combinations were found
      more frequently in food compared to other settings. However, the food source of a
      definite AMR plasmid is highly complex to confirm due to cross-sectorial
      transfers and international spread of AMR plasmids. For risk assessment purposes
      related to human health, AMR plasmids found in food and bearing genes conferring
      resistances to critically important antibiotics in human medicine - such as to
      extended-spectrum cephalosporins, carbapenems or colistin - have been under
      specific scrutiny these last years. Those plasmids are often multidrug resistant
      and their dissemination can be driven by the selective pressure exerted by any of
      the antibiotics concerned. Also, AMR plasmids carry numerous other genes
      conferring vital properties to the bacterial cell and are recurrently subjected
      to evolutionary steps such as hybrid plasmids, making the epidemiology of AMR
      plasmids in food a moving picture.

PMID- 30194945
TI  - Genomic sequence and phylogenetic analyses of two novel orthoreovirus strains
      isolated from Pekin ducks in 2014 in Germany.
AB  - Complete genomic sequences of two orthoreovirus strains, D2533/4/1-10 and
      D2533/6/1-10, isolated from Pekin ducklings in Germany have been determined.
      Pairwise sequence comparisons and phylogenetic analyses indicated that strain
      D2533/4/1-10 might have acquired its genomic segments from three different
      origins, from classical and novel waterfowl reoviruses, and a yet unknown
      orthoreovirus strain. D2533/6/1-10 proved to be only distantly related to
      previously described orthoreoviruses. Reassortment, host species transmission
      events, and successful adaptation of novel variants may signify a challenge for
      animal health and maintenance of economic production.

PMID- 30194946
TI  - NIR-light and GSH activated cytosolic p65-shRNA delivery for precise treatment of
      metastatic cancer.
AB  - Despite advances in cancer therapy, metastasis remains the dominate reason for
      cancer-related mortality. Herein, a novel, hybrid nanocomplex, RDG/shRNA, with
      tumor-targeting and dual stimuli responsive properties is described for the
      effective treatment of metastatic cancer. This multimodal therapeutic system was
      prepared by complexing RDG nanovectors with p65-shRNA, an anti-NF-kappaB agent,
      via the electrostatic interactions between negatively charged shRNA and the
      cationic DSPEI displayed on the surface of the nanovectors. Cytosolic release of
      shRNA from the complex is achieved by dual-stimulation from NIR laser irradiation
      and high intracellular GSH concentrations, resulting in effective gene silencing
      of metastatic 4T1 breast cancer cells, thereby inhibiting cell proliferation and
      invasion. More importantly, the nanocomplex undergoes significant intratumoral
      accumulation due to the EPR effect and RGD-mediated endocytosis. In combination
      with localized NIR laser irradiation, the hybrid complex could effectively
      inhibit primary breast tumor growth and almost completely suppresses distant
      metastasis, significantly improving the therapeutic efficacy of the RDG/shRNA
      complex. Consequently, this NIR-light and GSH responsive complex with tumor
      targeting capabilities and cytosolic shRNA release is a promising nanoplatform
      for precise treatment of metastatic cancer.

PMID- 30194948
TI  - Separation of cells in density gradients with temporary solidification of the
      gradient: Application to Escherichia coli forms obtained by microwave treatment
      of pure cultures.
AB  - Gelatin added in certain concentration into the density gradient mixtures allows
      to solidify and melt the gradient reversibly. Such a method was applied to
      separation of partially disintegrated Escherichia coli VKM B-125 cells in
      discontinuous sucrose gradient which was optimized to obtain small round "nano
      cells" free from other cell components. Gelatin added to the sucrose solutions
      had the advantages: i) accurate gradient layers were formed, ii) gelatin did not
      interfere with the cells and sub-particles during centrifugation, iii) solidified
      gelatin allowed to cut out the separated cell components, and iv) gelatin allowed
      to prepare ready-made solidified gradient centrifugation tubes into storage.

PMID- 30194947
TI  - An intestinal paracellular pathway biased toward positively-charged
      macromolecules.
AB  - Lacking an effective mechanism to safely and consistently enhance macromolecular
      uptake across the intestinal epithelium, prospects for successful development of
      oral therapeutic peptide drugs remain unlikely. We previously addressed this
      challenge by identifying an endogenous mechanism that controls intestinal
      paracellular permeability that can be activated by a peptide, termed PIP 640,
      which can increase cellular levels of phosphorylated myosin light chain at
      position S19 (MLC-pS19). Apical application in vitro or luminal application in
      vivo was shown to increase macromolecular solute transport within minutes that
      recovered completely within a few hours after removal. We now examine the nature
      of PIP 640-mediated permeability changes. Confluent Caco-2 cell monolayers
      treated with PIP 640 enhanced apical-to-basolateral (AB) transport of 4-kDa, but
      not 10-kDa, dextran. Expression and/or cellular distribution changes of tight
      junction (TJ) proteins were restricted to increased claudin-2 over a time course
      that correlated with an apparent shift in its distribution from the nucleus to
      the membrane fraction of the cell. PIP 640-mediated epithelial changes were
      distinct from the combined actions of the pro-inflammatory cytokines tumor
      necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma). While TNF
      alpha/IFN-gamma treatment also increased MLC-pS19 levels, these cytokines
      enhanced AB transport for 70-kDa dextran and decreased occludin expression at
      TJs. Claudin-2-dependent changes induced by PIP 640 resulted in an AB transport
      bias for positively-charged macromolecules demonstrated in vitro using charge
      variants of 4-kDa dextrans and by comparing transport of salmon calcitonin to
      exenatide. Comparable outcomes of increased TJ localization of claudin-2 and
      enhanced transport of these therapeutic peptides that biased toward cationic
      characteristics was demonstrated in vivo following after intra-luminal injection
      into rat jejunum. Together, these data have shown a potential mechanism for PIP
      640 to enhance paracellular permeability of solutes in the size range of small
      therapeutic peptides that is biased toward positively-charged solutes.

PMID- 30194950
TI  - Link between depression and cardiovascular diseases due to epigenomics and
      proteomics: Focus on energy metabolism.
AB  - Major depression is the most common mental disorder and a leading cause of years
      lived with disability. In addition to the burden attributed to depressive
      symptoms and reduced daily life functioning, people with major depression are at
      increased risk of premature mortality, particularly due to cardiovascular
      diseases. Several studies point to a bi-directional relation between major
      depression and cardiovascular diseases, thereby indicating that both diseases may
      share common pathophysiological pathways. These include lifestyle factors (e.g.
      physical activity, smoking behavior), dysfunctions of endocrine systems (e.g.
      hypothalamus-pituitary adrenal axis), and a dysbalance of pro- and anti
      inflammatory factors. Furthermore, recent research point to the role of
      epigenomic and proteomic factors, that are reviewed here with a particular focus
      on the mitochondrial energy metabolism.

PMID- 30194949
TI  - Myocardial hypersensitivity to ischemic injury is not reversed by clonidine or
      propranolol in a predator-based rat model of posttraumatic stress disorder.

PMID- 30194951
TI  - Predictive factors of efficacy of combination therapy with basal insulin and
      liraglutide in type 2 diabetes when switched from longstanding basal-bolus
      insulin: Association between the responses of beta- and alpha-cells to GLP-1
      stimulation and the glycaemic control at 6 months after switching therapy.
AB  - AIMS: To evaluate the glycaemic control of combination therapy with basal insulin
      and liraglutide, and to explore the factors predictive of efficacy in patients
      with type 2 diabetes when switched from longstanding basal-bolus insulin therapy.
      METHODS: We studied 41 patients who switched from basal-bolus insulin therapy of
      more than 3 years to basal insulin/liraglutide combination therapy. Glycaemic
      control was evaluated at 6 months after switching therapy and used to subdivide
      the patients into good-responders (HbA1c <7.0% or 1.0% decrease) and poor
      responders (the rest of participants). To evaluate the glucose-dependent
      insulin/glucagon responses without/with liraglutide, a 75-g oral glucose
      tolerance test (OGTT) was performed twice, before (1st-OGTT) and 2-days after
      (2nd-OGTT) liraglutide administration. RESULTS: Twenty-eight patients (68.3%)
      were identified as good-responders. No differences were found in baseline
      characteristics including insulin/glucagon responses during 1st-OGTT between the
      groups. 2nd-OGTT revealed that paradoxical hyperglucagonemia were significantly
      improved in both groups, but significant increases in insulin secretory response
      were observed only in good-responders. Logistic regression analyses revealed that
      the improvement of the insulin-response during 2nd-OGTT compared to that during
      1st-OGTT is associated with the good-responder. CONCLUSIONS: Enhancement of
      glucose-dependent insulin-response under liraglutide administration is a
      potential predictor of long-term glycaemic control after switching the therapies.

PMID- 30194952
TI  - Conflicts of interest, bias, and the IARC Monographs Program.

PMID- 30194953
TI  - Insights on auditory closed-loop stimulation targeting sleep spindles in slow
      oscillation up-states.
AB  - BACKGROUND: The consolidation of sleep-dependent memories is mediated by an
      interplay of cortical slow oscillations (SOs) and thalamo-cortical sleep
      spindles. Whereas an enhancement of SOs with auditory closed-loop stimulation has
      been proven highly successful, the feasibility to induce and boost sleep spindles
      with auditory stimulation remains unknown thus far. NEW METHOD: Here we tested
      the possibility to enhance spindle activity during endogenous SOs and thereby to
      promote memory consolidation. Performing a sleep study in healthy humans, we
      applied an auditory Spindle stimulation and compared it with an Arrhythmic
      stimulation and a control condition comprising no stimulation (Sham). RESULTS:
      With Spindle stimulation we were not able to directly entrain endogenous spindle
      activity during SO up-states. Instead, both Spindle and Arrhythmic stimulation
      evoked a resonant SO response accompanied by an increase in spindle power phase
      locked to the SO up-state. Assessment of overnight retention of declarative word
      pairs revealed no difference between all conditions. COMPARISON WITH EXISTING
      METHODS: Our Spindle stimulation produced oscillatory evoked responses (i.e.,
      increases in SOs and spindle activity during SO up-states) quite similar to those
      observed after the auditory closed-loop stimulation of SOs in previous studies,
      lacking however the beneficial effects on memory retention. CONCLUSION: Our
      findings put the endeavour for a selective enhancement of spindle activity via
      auditory pathways into perspective and reveal central questions with regard to
      the stimulation efficacy on both an electrophysiological and a neurobehavioral
      level.

PMID- 30194954
TI  - Indirect relation based individual metabolic network for identification of mild
      cognitive impairment.
AB  - BACKGROUND: Optimized abnormalities of individual brain network may allow earlier
      detection of mild cognitive impairment (MCI) and accurate prediction of its
      conversion to Alzheimer's disease (AD). Currently, most studies constructed
      individual networks based on region-to-region correlation without employing multi
      region information. In order to develop the potential discriminative power of
      network and provide supportive evidence for feasibility of individual metabolic
      network study, we propose a new approach to extract features from network with
      indirect relation based on 18F-FDG PET data. NEW METHOD: Direct relation based
      individual network is first constructed using Gaussian kernel function. After
      that, the lattice-close-degree in fuzzy mathematics is applied to reflect region
      to-region indirect relation using the direct relations of regions and their
      common neighbors. The proposed approach has been evaluated on 199 MCI subjects
      and 166 normal controls (NC) using SVM classifier. RESULTS: The indirect relation
      based network features significantly promote classification performance in
      separating MCI from normal controls (NC) as well as MCI converters from non
      converters. Specially, further improvements can be obtained by combining indirect
      relation features with ADAS-cog scores. Moreover, the discriminative regions we
      found are consistent with previous studies, indicating the efficacy of our
      constructed network in identifying correct biomarkers for diagnosing MCI and
      predicting its conversion. COMPARISON WITH EXISTING METHOD(S): More accurate MCI
      identification of PET data can be achieved by features of network with indirect
      relation. CONCLUSIONS: This work provides a new way to investigate brain network
      from metabolic perspective for accurate identification of MCI.

PMID- 30194955
TI  - Adipokine and cytokine levels in patients with adrenocortical cancer, subclinical
      Cushing's syndrome and healthy controls.
AB  - INTRODUCTION: In recent years researchers have focused at hormonal activity in
      Cushing's syndrome (CS) in connection with metabolic disorders and the role of
      adipokines and cytokines secreted by the adipose tissue. The aim of the study was
      to investigate levels of adipokines and cytokines in patients with: subclinical
      CS (SCS) - in relation to hormonal parameters of hypercortisolemia, and,
      adrenocortical cancer (ACC). MATERIALS AND METHODS: The study included 20 SCS as
      well as 7 ACC patients, and 18 healthy participants. Hormonal activity and serum
      concentrations of adiponectin, leptin, resistin, tumor necrosis factor alpha
      (TNFalpha), interleukin 6 (IL6), and monocyte chemoattractant protein 1 (MCP1),
      were analyzed. RESULTS: In SCS patients compared to healthy volunteers a trend
      toward higher concentrations of all pro-inflammatory cytokines was noted,
      however, statistically significant differences were only found for TNFalpha and
      IL6 (p = 0.047 and p = 0.028, respectively). Adiponectin concentrations were
      significantly lower in the SCS group (p = 0.006). Serum adipokine and cytokine
      levels were independent of the presence of diabetes mellitus (DM) and
      hypertension (HT) in the SCS group. A significant correlation was found between
      subclinical glucocorticoid secretion and IL6 concentration (Pearson's r = 0.517,
      p = 0.02). Acquired results were independent of BMI. In ACC patients compared to
      controls higher IL6, TNFalpha and MCP1 levels were recorded. CONCLUSION: It is
      possible that higher adipokine and pro-inflammatory cytokine concentrations as
      well as lower anti-inflammatory adiponectin concentrations comprise an additional
      risk factor of metabolic and cardiovascular diseases in SCS patients. It seems
      that at least among patients with SCS adipokine and cytokine secretion is
      independent of hormonal activity (except for IL6).

PMID- 30194956
TI  - Communicating antimicrobial resistance and stewardship in the national press:
      Lessons from sepsis awareness campaigns.

PMID- 30194958
TI  - Remote Trice Light, Temperature, and pH-actuation of Switchable Magneto-Plasmonic
      Nanocarriers for Combinational Photothermal and Controlled/Targeted
      Chemotherapies.
AB  - Three magneto-plasmonic nanohybrids were synthesized using Au- and Ag-coated
      Fe3O4 nanoparticles (NPs)-modified dual pH- and temperature-responsive triblock
      copolymer of poly (butyl methacrylate-co-acrylamide-co-methacrylic acid) to serve
      as drug carriers with potential of using in both photothermal and
      controlled/targeted chemotherapies. The internal superparamagnetic core gives the
      carriers targeted-delivery characteristics, and surface plasmon resonance-based
      noble metallic Au/Ag shells give them on-demand photothermal and photo-triggering
      release properties. To investigate the effect of coating method on the targeting
      property of synthesized carriers, Au NPs were attached to the magnetic core by 2
      different direct/indirect procedures and the properties of the synthesized
      carriers including swelling ratio and thermal and optical sensitivity and
      switching were comprehensively investigated in 2 different buffer solutions with
      pH 5.5 and 7.4 at 37 degrees C. Letrozole was used as a model anticancer drug and
      its loading and release properties were evaluated for the four nanocarriers. The
      cytotoxicity of drug-free and letrozole-loaded nanocarriers on normal L929
      fibroblast and MDAMB 231 breast cancer cell lines was evaluated in
      absence/presence of laser radiation. The results revealed that the carriers have
      the potential of serving as switchable trimodal light/temperature/pH-triggered
      and targeted/controlled drug delivery platforms for chemophotothermal therapy.

PMID- 30194959
TI  - Bayesian state-space modeling in gene expression data analysis: An application
      with biomarker prediction.
AB  - Background and ObjectiveBayesian State Space models are recent advancement in
      stochastic modeling which capture the randomness of a hidden background process
      by scrutinizing the prior knowledge and likelihood of observed data. This article
      elucidate the scope of Bayesian state space modeling on predicting the future
      expression values of a longitudinal micro array data. MethodsThe study
      conveniently makes use of longitudinally collected clinical trial data (GSE30531)
      from NCBI Gene Expression Omnibus (GEO) data repository. Multiple testing
      methodology using t-test is used for selecting differentially expressed genes
      between groups for fitting the model. The parameter values of the predictive
      model and future expression levels are estimated by drawing samples from the
      posterior joint distribution using a stochastic Markov Chain Monte Carlo (MCMC)
      algorithm which relies on Gibbs Sampling. The study also made an attempt to get
      estimates and its 95% Credible Interval through assumptions of different
      covariance structures like Variance Components, First order Auto Regressive and
      Unstructured variance-covariance structure to showcase the flexibility of the
      algorithm. Results72 Distinct genes with significantly different expression
      levels where selected for model fitting. Parameter estimates showed almost
      similar trends under different covariance structure assumption. Cross tabulation
      of gene frequencies having minimum credible interval under each covariance
      structure and study group showed a significant P value of 0.02.
      ConclusionsPresent study reveals that Bayesian state space models can be
      effectively used to explain and predict a complex data like gene expression data.

PMID- 30194957
TI  - alpha-synuclein expression from a single copy transgene increases sensitivity to
      stress and accelerates neuronal loss in genetic models of Parkinson's disease.
AB  - Parkinson's disease (PD) is the second most common neurodegenerative disease and
      is characterized by the formation of alpha-synuclein-containing protein
      aggregates called Lewy bodies within the brain. A crucial role for alpha
      synuclein in the pathogenesis of PD is also suggested by the fact that point
      mutations, increased copy number, or polymorphisms in the alpha-synuclein gene
      SNCA all cause or contribute to the development of PD. In addition to SNCA, an
      increasing number of other genes have been implicated in PD. While mutations in
      at least some of these genes have been shown to cause the formation of Lewy
      bodies, the role of alpha-synuclein in these genetic forms of PD remains poorly
      defined. Since C. elegans do not have a homolog of alpha-synuclein, this organism
      provides the opportunity to identify synergism between alpha-synuclein and other
      genes implicated in PD. To do this, we generated a novel C. elegans model in
      which wild-type alpha-synuclein is ubiquitously expressed from a single copy
      transgene, and examined the resulting effect on phenotypic deficits in PD
      deletion mutants affecting PARK2/pdr-1, PINK1/pink-1, DJ-1/djr-1.1 and
      ATP13A2/catp-6. While the PD deletion mutants exhibit only mild phenotypic
      deficits in absence of alpha-synuclein, expression of wild-type alpha-synuclein
      caused increased sensitivity to multiple stresses, induced deficits in dopamine
      dependent behavior, and accelerated loss of dopamine neurons. Overall, these
      results suggest that the recessive loss of function mutations act together with
      alpha-synuclein to cause PD, and that alpha-synuclein lowering strategies may be
      effective in genetic forms of PD.

PMID- 30194960
TI  - Adolescent sexual violence: Prevalence, adolescent risks, and violence
      characteristics.
AB  - The purpose of this research is to investigate peer-to-peer sexual violence
      victimization and perpetration among male and female adolescents in a large,
      racially and economically diverse, community-based sample. Using cross-sectional
      data over a four-year period (2009-2013) from a regional sample of middle school
      and high school students in southeastern Michigan, we examined the prevalence and
      correlates of peer-to-peer sexual violence victimization and perpetration among
      adolescents. 33.9% of males and 53.5% of females reported sexual violence
      victimization, while 22.8% of males and 12.6% of females reported sexual violence
      perpetration. The majority of peer-to-peer sexual victimization and perpetration
      occurred by someone of the opposite sex, however, same-sex victimization and
      perpetration were not uncommon. Substance use, depression, Attention Deficit
      Hyperactivity Disorder (ADHD), and conduct disorder were associated with peer-to
      peer sexual violence (victimization or perpetration) for both males and females,
      with few differences in the patterns of associations by sex. These findings are
      an important step in better understanding the types of peer-to-peer sexual
      violence that adolescents experience and risk factors for both male and female
      youth.

PMID- 30194961
TI  - Trends in obesity and multimorbidity in Canada.
AB  - Very few studies have examined trends in multimorbidity over time and even fewer
      have examined trends over time across different body mass index (BMI) groups.
      Given a general decline in death rates but increased cardiovascular risk factors
      among individuals with obesity, the trend in the association between obesity and
      multimorbidity is hypothesized to be increasing over time. The data for our study
      came from the 1996-97 National Population Health Survey and the 2005 and 2012-13
      Canadian Community Health Surveys (N = 277,366 across all 3 surveys). We examined
      trends in the association between BMI groups and multimorbidity using a logistic
      regression model. We also investigated trends in the prevalence of specific
      chronic conditions, pairs of chronic conditions and different levels of
      multimorbidity across BMI groups. We found significantly greater levels of
      multimorbidity in 2005 (OR = 1.42; p < 0.001) and 2012-13 (OR = 1.58; p < 0.001)
      relative to 1996-97. Changes in multimorbidity levels were much greater among
      individuals with class II/III (OR = 1.48; p = 0.005) and class I obesity (OR =
      1.38; p = 0.001) in 2012-13 relative to 1996-97. Much of the increase in
      multimorbidity among individuals living with obesity was due to increases in 3+
      chronic conditions and conditions in combination with hypertension, and the
      greatest increase was found among seniors living with obesity. Our results
      highlight the need for interventions aimed at preventing obesity and the
      prevention of chronic conditions among individuals with obesity, especially among
      seniors.

PMID- 30194962
TI  - Growing out of attention deficit hyperactivity disorder: Insights from the
      'remitted' brain.
AB  - We consider developmental and cognitive models to explain why some children 'grow
      out' of attention deficit hyperactivity disorder (ADHD) by adulthood. The first
      model views remission as a convergence towards more typical brain function and
      structure. In support, some studies find that adult remitters are
      indistinguishable from those who were never affected in the neural substrates of
      'top-down' mechanisms of cognitive control, some 'bottom-up' processes of
      vigilance/response preparation, prefrontal cortical morphology and intrinsic
      functional connectivity. A second model postulates that remission is driven by
      the recruitment of new brain systems that compensate for ADHD symptoms. It draws
      support from demonstrations of atypical, but possibly beneficial, patterns of
      connectivity within the cognitive control network in adult remitters. The final
      model holds that some childhood ADHD anomalies show lifelong persistence,
      regardless of adult outcome, supported by shared reports of anomalies in
      remitters and persisters in posterior cerebral and striato-thalamic regions. The
      models are compatible: different processes driving remission might occur in
      different brain regions. These models provide a framework for future studies
      which might inform novel treatments to 'accelerate' remission.

PMID- 30194963
TI  - Bacterial colonization of bladeless electrical fans.

PMID- 30194964
TI  - Myokines, physical activity, insulin resistance and autoimmune diseases.
AB  - Myokines are peptides produced and released by myocytes of muscle fibers that
      influence physiology of muscle and other organs and tissues. They are involved in
      mediating the beneficial effects that exercise has on health. More than one
      hundred have been identified and among them are IL6, myostatin, irisin, mionectin
      and decorin. Physical inactivity leads to an altered response of the secretion of
      myokines and resistance to them; this leads to a pro-inflammatory state that
      favors sarcopenia and fat accumulation, promoting the development of
      cardiovascular diseases, insulin resistance, and diabetes mellitus type 2. Some
      myokines, including irisin, are responsible for the improvement that exercise
      produces in many chronic diseases such as type 2 diabetes and cardiovascular
      diseases, some types of cancer and many autoimmune diseases such as idiopathic
      inflammatory myopathy, rheumatoid arthritis, systemic lupus erythematosus and
      inflammatory bowel disease.

PMID- 30194965
TI  - Bcl2L12 plays a critical role in the development of intestinal allergy.
AB  - The skewed T helper (Th) 2 response plays a central role in the pathogenesis of
      allergic diseases, while its initiating factors remain elusive. Recent studies
      indicate that Bcl2 like protein-12 (Bcl2L12) is associated with the Th2-biased
      inflammation. This study is designed to test a hypothesis that Bcl2L12 plays a
      critical role in the initiation of allergic response. In this study, peripheral
      CD4+ T cells were isolated from food allergy (FA) patients and healthy subjects;
      A mouse FA model was developed to test the role of Bcl2L12 in induction of
      allergic response in the intestine. The results showed that expression of Bcl2L12
      by CD4+ T cells was higher in FA patients and FA mice and positively correlated
      with expression of Th2 cytokines. CD4+ T cells from FA patients showed a Bcl2L12
      dependent tendency to differentiate into Th2 cells. Bcl2L12 played a crucial role
      in induction of allergic response in the intestine. Physical contact between
      Bcl2L12 and GATA3 facilitated GATA3 to bind Il4 promoter to promote expression of
      IL-4. Adoptive transfer with Bcl2L12-deficient CD4+ T cells to Rag2-/- mice did
      not reconstitute the efficient CD4+ T cell response as the mice could not be
      induced FA, while Rag2-/- mice received WT CD4+ T cell transfer were induced FA.
      In conclusion, Bcl2L12 plays a crucial role in the induction of Th2 polarization
      and allergic response in the intestine. The Bcl2L12 in CD4+ T cells may be a
      potential target for the treatment of FA.

PMID- 30194966
TI  - Localized expression of antimicrobial proteins mitigates huanglongbing symptoms
      in Mexican lime.
AB  - Citrus huanglongbing (HLB) is a devastating disease associated with Candidatus
      Liberibacter asiaticus spp. (CLas), a bacterium restricted to the sieve tube
      system of the phloem that is transmitted by the psyllid vector, Diaphorina citri.
      In this study, the human antimicrobial peptides, lysozyme and beta-defensin 2,
      were targeted to the vascular tissue of Mexican lime (Citrus x aurantifolia
      [Christm.] Swingle) by fusion to a phloem-restricted protein. Localized
      expression was achieved, via Agrobacterium tumefaciens-mediated transformation of
      the stem, which led to protein expression and mobilization within the vascular
      tissue of heterotrophic tissues. HLB-infected plants were monitored for 360 days.
      Lower bacteria titers were observed in plants expressing either beta-defensin 2,
      lysozyme, or the combination thereof, and these plants had increased
      photosynthesis, compared to untreated control trees. Thus, targeting of
      antimicrobial proteins to the vascular tissue was effective in decreasing CLas
      titer, and alleviating citrus greening symptoms. Based on these findings, this
      strategy could be used to effectively treat plants that are already infected with
      bacterial pathogens that reside in the phloem translocation stream.

PMID- 30194967
TI  - Complete genome of Gongronella sp. w5 provides insight into its relationship with
      plant.
AB  - Gongronella sp. w5 (w5) is a soil fungus isolated from Anhui, China. Here we
      report the high-quality genome sequence of w5 and its phenotypic characteristics
      based on genomic information. The genome of w5 consists of 34,723,828 bp
      assembled into 149 scaffolds and 11,302 predicted protein-coding genes. Genome
      analysis suggested that w5 may possess host cell infection capacity and maybe a
      biotrophic fungus that relies on plant sucrose as carbon source. W5 shows the
      ability of rapid invasion into the plant root cells based on CAZymes analysis.
      Further results evidenced that w5 can use sucrose as the carbon source. Plant
      inoculation revealed that w5 penetrates the root cells of Actinidia chinensis
      with its hypha, and simultaneously promotes plant growth. It may promote plant
      growth by secreting organic acid and facilitating phosphate acquisition. The new
      genomic data and phenotype features will facilitate future applications of this
      strain in biotechnology.

PMID- 30194968
TI  - Predator-prey equations with constant harvesting and planting.
AB  - We propose Lotka-Volterra type predator-prey equations which include small
      constant terms. Depending on its sign, the constant may model various things. To
      see the effect of the constants clearly we drop all other functional responses
      except the ones in the original Lotka-Volterra equations. We add a small negative
      constant for the harvesting or the Allee effect. A positive constant is added to
      model the planting or external influx. We find the predator-prey equations with
      constant terms produce most of dynamic and static patterns observed from other
      predator-prey models with various functional responses.

PMID- 30194970
TI  - Roles of basal keratinocytes in actinotrichia formation.
AB  - The embryonic fins and the tip of adult fins of teleost fish are supported by
      rows of straight, unmineralized fibrils called actinotrichia. The proximal ends
      of the actinotrichia are bundled and the mineralized bones called lepidotrichia
      are made along them. Since malformation in actinotrichia causes wavy fin bones,
      the correct configuration of actinotrichia is essential for the correct
      construction of the fin shape. Past studies suggested that two types of cells,
      basal keratinocytes, and mesenchymal cells involve in the formation of
      actinotrichia. However, the mechanism how these cells contribute is unknown. In
      this study, we elucidated the role of basal keratinocytes in actinotrichia
      formation. First, we developed the imaging tool that specifically visualizes the
      basal keratinocytes and actinotrichia. Then, we established the in vitro culture
      method of the basal keratinocytes and found that the keratinocytes developed fine
      needle-like structures in it. The TEM image of them showed the specific shadow
      pattern of actinotrichia, indicating that the fine needle-like structures are the
      newly made actinotrichia. Finally, we cultured the basal keratinocytes with
      mature actinotrichia and observed that the basal keratinocytes actively holded
      actinotrichia with their membrane, and often generated a linear array of cells
      holding a single actinotrichium. This behavior suggested a mechanism with which
      long actinotrichia are made by relatively small cells. Our results clarified the
      role of basal keratinocyte and provided a novel insight into understanding the
      mechanism of actinotrichia formation.

PMID- 30194969
TI  - Molecular Basis for Immunity Protein Recognition of a Type VII Secretion System
      Exported Antibacterial Toxin.
AB  - Gram-positive bacteria deploy the type VII secretion system (T7SS) to facilitate
      interactions between eukaryotic and prokaryotic cells. In recent work, we
      identified the TelC protein from Streptococcus intermedius as a T7SS-exported
      lipid II phosphatase that mediates interbacterial competition. TelC exerts
      toxicity in the inner wall zone of Gram-positive bacteria; however, intercellular
      intoxication of sister cells does not occur because they express the TipC
      immunity protein. In the present study, we sought to characterize the molecular
      basis of self-protection by TipC. Using sub-cellular localization and protease
      protection assays, we show that TipC is a membrane protein with an N-terminal
      transmembrane segment and a C-terminal TelC-inhibitory domain that protrudes into
      the inner wall zone. The 1.9-A X-ray crystal structure of a non-protective TipC
      paralogue reveals that the soluble domain of TipC proteins adopts a crescent
      shaped fold that is composed of three alpha-helices and a seven-stranded beta
      sheet. Subsequent homology-guided mutagenesis demonstrates that a concave surface
      formed by the predicted beta-sheet of TipC is required for both its interaction
      with TelC and its TelC-inhibitory activity. S. intermedius cells lacking the tipC
      gene are susceptible to growth inhibition by TelC delivered between cells;
      however, we find that the growth of this strain is unaffected by endogenous or
      overexpressed TelC, although the toxin accumulates in culture supernatants.
      Together, these data indicate that the TelC-inhibitory activity of TipC is only
      required for intercellularly transferred TelC and that the T7SS apparatus
      transports TelC across the cell envelope in a single step, bypassing the cellular
      compartment in which it exerts toxicity en route.

PMID- 30194971
TI  - Comparison of comorbid diagnoses in children with and without eosinophilic
      esophagitis in a large population.
AB  - BACKGROUND: Previous reports suggest a higher prevalence of comorbid diseases in
      patients with eosinophilic esophagitis (EoE), although few have systematically
      quantified comorbidities in pediatric patients. OBJECTIVE: To define the rate of
      comorbid diagnoses in pediatric EoE patients compared with rates in those without
      EoE. METHODS: Retrospective cross-sectional review of electronic medical records
      for patients seen in a single large pediatric primary care network between
      January 2007 and December 2016 (n = 456,148). International Classification of
      Diseases, Ninth and Tenth Revision codes were used to determine prevalence rates
      for coexisting diagnoses. RESULTS: A total of 428 patients held a diagnosis for
      EoE. Significant differences in rate of comorbid diseases included allergic
      rhinoconjunctivitis (60.0% of EoE cohort vs 17.4% of non-EoE cohort, P < .0001);
      asthma (59.8% of EoE, 21.4% of non-EoE, P < .0001); atopic dermatitis (17.8% of
      EoE, 6.6% of non-EoE, P < .0001); adrenal insufficiency (2.6% of EoE, 0.4% of non
      EoE, P < .0001); autism spectrum disorder (7.5% of EoE, 1.9% of non-EoE, P <
      .0001); celiac disease (5.6% of EoE, 0.9% of non-EoE, P < .0001); connective
      tissue diseases (1.4% of EoE, 0.1% of non-EoE, P < .0001); cystic fibrosis (0.9%
      of EoE, 0.05% of non-EoE, P < .0001); inflammatory bowel disease (0.7% of EoE,
      0.2% of non-EoE, P = .03); type 1 diabetes mellitus (1.2% of EoE, 0.3% of non
      EoE, P = .0069). CONCLUSION: Children with EoE have markedly higher rates of both
      atopic and non-atopic diseases compared with children without EoE. These
      associations have important implications for comprehensive EoE care and future
      research regarding associated disease mechanisms.

PMID- 30194972
TI  - Recognition of the peripheral airway impairment phenotype in children with well
      controlled asthma.
AB  - BACKGROUND: Peripheral airway impairment, although frequently unrecognized, is a
      risk factor for poor asthma control, loss of control, increased exacerbations,
      airway hyperresponsiveness, and loss of lung function with age, even in patients
      with well-controlled asthma. OBJECTIVE: To determine the presence of peripheral
      airway impairment by impulse oscillometry and forced expiratory flow between 25%
      and 75% (FEF25%-75%) in children whose asthma is well controlled by National
      Asthma Education and Prevention Program (NAEPP) guidelines. METHODS: In this
      retrospective, cross-sectional analysis, outcomes were evaluated across 192
      encounters in 139 patients with moderate to severe asthma, ages 4-18 years.
      Receiver operator characteristic curves were created and oscillometry thresholds
      determined by maximizing the sum of sensitivity and specificity to identify those
      whose condition is not well controlled. Impairment was then identified for those
      whose condition was well controlled when these age-dependent oscillometry
      thresholds were met for each IOS measure or FEF25%-75% < 65% of predicted.
      RESULTS: Reactance at 5 Hz (X5) appeared most robust to identify peripheral
      airway impairment. In 96 well-controlled asthma encounters, impairment was
      identified by X5 in approximately 20% and 45% for those younger than 12 years and
      adolescents, respectively, compared with a maximum of 10% with FEF25%-75% in the
      adolescent cohort (P < .05). CONCLUSION: We conclude that peripheral airway
      impairment, determined by oscillometry, is common in patients with well
      controlled asthma across age cohorts. X5 with optimal cut points <= -3.8, <= 
      2.5, and <= -1.5 cmH2O/L/s for ages 4-7, 8-11, and >12 years, provides the
      clinician with a practical tool to identify the presence of the peripheral airway
      impairment phenotype that is consistently superior to FEF25%-75%. This
      recognition, if confirmed, may reduce the risk of asthma-associated consequences
      with earlier and more targeted therapy.

PMID- 30194973
TI  - Structure analysis of transposons carrying the aac(6')-aph(2") gene in
      Enterococcus faecalis isolated in Beijing, China, and comparison of their
      transfer efficiency.
AB  - Transfer of aac(6')-aph(2") transposons mediating high-level gentamicin
      resistance (HLGR) in Enterococcus faecalis is a serious problem in the clinic.
      However, factors affecting the transfer of aac(6')-aph(2") have not yet been
      elucidated. The current study aimed to examine the genetic and molecular basis of
      HLGR in E. faecalis strains isolated in Beijing (China) and to clarify the
      relationship between transfer efficiency of aac(6')-aph(2") transposons and the
      transposon structure/location. A total of five transposon structures were
      identified by PCR mapping of the corresponding transposon regions, including a
      Tn5281-like non-truncated transposon and four truncated transposons. A plasmid
      location study of aac(6')-aph(2") by Southern blot following S1-PFGE and filter
      mating conjugation experiments demonstrated that plasmid location rates
      correlated with conjugation-positive rates. Chromosome walking to identify the
      sequence upstream of a representative type III truncated transposon found a
      truncated aph(2")-Ia region, and further PCR analysis of this region among
      strains from different groups revealed similar a positive rate trend as the
      transposon plasmid location rate and conjugation-positive rate. In conclusion,
      aac(6')-aph(2") transposons were of different structures in E. faecalis strains
      from Beijing, with two new transposon structures that have not been reported
      elsewhere. Presence of the truncated aph(2")-Ia region upstream of some truncated
      transposons suggests recombination between aminoglycoside-modifying enzyme genes.
      Possible links exist among plasmid location, conjugation and the presence of
      truncated aph(2")-Ia upstream of the transposon.

PMID- 30194974
TI  - Identification of chromoblastomycosis agents by PCR based reverse line blot (PCR
      RLB) hybridization assay.
AB  - Chromoblastomycosis is one of the most prevalent implantation fungal infections
      caused by melanized fungi, affecting individuals with certain risk factors with
      high morbidity due to its recalcitrant nature. It is difficult to identify the
      etiological agents and thus a suitable reproductive molecular identification
      method applicable in developing countries has been investigated. We report the
      identification of four different fungal causative agents of chromoblastomycosis
      by reverse line blotting hybridization (RLB) based on biotin-labeled PCR products
      and amine labeled probes to hybridize. Sixty five reference strains, including
      type strains, i.e. Fonsecaea pedrosoi, F. monophora, F. nubica, and Phialophora
      verrucosa, obtained from the CBS-KNAW were included in this study. Internal
      transcribed spacer 1 (ITS1) regions of relevant species were aligned and adjusted
      using BIONUMERICS v. 4.61 in order to design four specific probes to identify
      informative nucleotide polymorphisms. The final identification of these species
      by RLB assay was concordant with ITS sequencing and showed 100% specificity with
      no cross hybridization, able to identify all tested strains. The time and cost
      were less compare to other routine identification methods such as sequencing.
      This assay allows sensitive and specific simultaneous detection and
      identification of a different fungal species.

PMID- 30194975
TI  - Observing and tracking single small ribosomal subunits in vivo.
AB  - Ribosomes are formed of a small and a large subunit (SSU/LSU), both consisting of
      rRNA and a plethora of accessory proteins. While biochemical and genetic studies
      identified most of the involved proteins and deciphered the ribosomal synthesis
      steps, our knowledge of the molecular dynamics of the different ribosomal
      subunits and also of the kinetics of their intracellular trafficking is still
      limited. Adopting a labelling strategy initially used to study mRNA export we
      were able to fluorescently stain the SSU in vivo. We chose DIM2/PNO1 (Defective
      In DNA Methylation 2/Partner of NOb1) as labelling target and created a stable
      cell line carrying an inducible SNAP-DIM2 fusion protein. After bulk labelling
      with a green fluorescent dye combined with very sparse labelling with a red
      fluorescent dye the nucleoli and single SSU could be visualized simultaneously in
      the green and red channel, respectively. We used single molecule microscopy to
      track single SSU in the nucleolus and nucleoplasm. Resulting trajectory data were
      analyzed by jump-distance analysis and the variational Bayes single-particle
      tracking approach. Both methods allowed identifying the number of diffusive
      states and the corresponding diffusion coefficients. For both nucleoli and
      nucleoplasm we could identify mobile (D = 2.3-2.8 um2/s), retarded (D = 0.18-0.31
      um2/s) and immobilized (D = 0.04-0.05 um2/s) SSU fractions and, as expected, the
      size of the fractions differed in the two compartments. While the fast mobility
      fraction matches perfectly the expected nuclear mobility of the SSU (D = 2.45
      um2/s), we were surprised to find a substantial fraction (33%) of immobile SSU in
      the nucleoplasm, something not observed for inert control molecules.

PMID- 30194976
TI  - 1,25-Dihydroxyvitamin D3 modulates the effects of sublethal BPA on mitochondrial
      function via activating PI3K-Akt pathway and 17beta-estradiol secretion in rat
      granulosa cells.
AB  - Bisphenol A (BPA), an endocrine-disrupting chemical, is capable of producing
      reproductive toxicity. BPA results in mitochondrial DNA (mtDNA) deletion and
      mitochondrial dysfunction; however, the effect of BPA on the mitochondria of
      ovarian granulosa cells is not clear. Further, 1,25-dihydroxyvitamin D3 (1,25D3)
      may play a role in reproduction, because its receptor, VDR, contributes to the
      inhibition of oxidative stress and predominantly exists in the nuclei of
      granulosa cells. Hence, the role of 1,25D3 in BPA-mediated effects on
      mitochondrial function was examined in this study. Primary rat granulosa cells
      treated with BPA, 1,25D3, or both were subjected to molecular/biochemical assays
      to measure cell survival, mtDNA content, mtDNA deletion, superoxide dismutase
      activity, levels of proteins related to mitochondrial biogenesis, and
      mitochondrial function. We found that cell viability was dose-dependently reduced
      and reactive oxygen species (ROS) levels were increased by BPA treatment. BPA
      administration elevated Mn-superoxide dismutase (MnSOD) expression but negatively
      regulated total SOD activity. 1,25D3 treatment alone increased 17beta-estradiol
      secretion, ATP production, and cellular oxygen consumption. In cells treated with
      both agents, 1,25D3 enhanced BPA-induced MnSOD protein upregulation and blocked
      the BPA-mediated decline in total SOD activity. Furthermore, 1,25D3 attenuated
      BPA-mediated mtDNA deletion but showed no effect on BPA-induced increases in
      mtDNA content. Although BPA had no influence on the levels of peroxisome
      proliferator-activated receptor-gamma coactivator-1 alpha, nuclear respiratory
      factor-1, mitochondrial transcription factor A, or cytochrome c oxidase subunit
      IV, 1,25D3 plus BPA markedly increased mitochondrial biogenesis-related protein
      expression via the PI3K-Akt pathway. Moreover, BPA-mediated negative regulation
      of cytochrome c oxidase subunit I levels and 17beta-estradiol secretion was
      attenuated by 1,25D3 pre-treatment. Our results suggest that 1,25D3 attenuates
      BPA-induced decreases in 17beta-estradiol and that treatment with 1,25D3 plus BPA
      regulates granulosa cell mitochondria by elevating mitochondrial biogenesis
      related protein levels.

PMID- 30194977
TI  - Frozen Elephant Trunk to Treat Coarctation Associated With Proximal Aortic
      Disease: Better to Be Smart Than Brave.

PMID- 30194978
TI  - Postoperative Serum Troponin Trends in Infants Undergoing Cardiac Surgery.
AB  - Troponin-I (TN-I) levels are elevated following pediatric cardiac surgery with
      speculation that particular patterns may have prognostic significance. There is
      lack of procedure-specific data regarding postoperative TN-I levels in infants
      undergoing cardiac surgery. We hypothesized that TN-I elevation varies with type
      of surgery and persistent elevation predicts poor prognosis. We prospectively
      measured serial TN-I levels (preoperatively, 4, 8, 12, 24, and 48hours
      postoperatively) in 90 infants (age < 1 year) undergoing cardiac surgery: off
      cardiopulmonary bypass (CPB) (n = 15), on CPB (n = 43), and on CPB with
      ventricular incision (CPB with ventricular incision; n = 32). All patients had
      undetectable baseline TN-I levels. The area under the curve of TN-I levels over
      the 48-hour period was significantly different among the surgical groups (P <
      0.002), and highest in patients with CPB with ventricular incision. Generally, TN
      I levels peaked by 4hours after surgery and returned to near-normal levels within
      48hours. A persistent TN-I rise beyond 8hours after surgery was a strong
      predictor of postoperative hypoperfusion injury (defined as a composite endpoint
      of end-organ injury resulting from inadequate perfusion, odds ratio 21.5; P =
      0.001) and mortality (30% in those with persistently high TN-I, compared with
      3.5% in the remaining patients; P < 0.001), independent of patient age, anatomy
      and/or complexity of surgery, and level of postoperative support. Our data
      provide benchmark values for TN-I levels following cardiac surgery in infants.
      Extent of TN-I elevation correlates with type of surgery. Persistent TN-I
      elevation beyond 8hours after surgery is strongly associated with postoperative
      hypoperfusion injury and mortality.

PMID- 30194979
TI  - Has2 natural antisense RNA and Hmga2 promote Has2 expression during TGFbeta
      induced EMT in breast cancer.
AB  - The glycosaminoglycan hyaluronan has a crucial role in tissue organization and
      cell signaling. Hyaluronan accumulates in conjunction with rapid tissue
      remodeling during embryogenesis, as well as in inflammatory conditions and
      cancer. We report a negative correlation between the expression of genes encoding
      hyaluronan synthase HAS2, its natural antisense transcript HAS2-AS, the chromatin
      modulating factor HMGA2 and transforming growth factor-beta (TGFbeta), and
      survival of patients with invasive breast carcinomas. In mouse mammary epithelial
      cells, TGFbeta activates Smad and non-Smad signaling pathways, resulting in the
      transcriptional induction of Has2, Has2as (the mouse ortholog of HAS2-AS) and
      Hmga2, as well as epithelial-mesenchymal transition (EMT)-promoting transcription
      factors, such as Snail. Importantly, Has2as abrogation suppressed the TGFbeta
      induction of EMT markers, including Snai1, Hmga2, Fn1, and suppressed the
      mesenchymal phenotype. TGFbeta induction of Hmga2, Has2as and Has2, and synthesis
      of hyaluronan were accompanied with activation of Akt and Erk1/2 MAP-kinase
      signaling and were required for breast cancer cell motility. Importantly, the
      hyaluronan receptor Cd44, but not Hmmr, was required for TGFbeta-mediated EMT
      phenotype. Interestingly, Has2as was found to contribute to the maintenance of
      stem cell factors and breast cancer stemness. Our findings show that Has2as has a
      key role in TGFbeta- and HAS2-induced breast cancer EMT, migration and
      acquisition of stemness.

PMID- 30194980
TI  - Development of controlled release amorphous solid dispersions (CRASD) using
      polyvinyl acetate-based release retarding materials: Effect of dosage form
      design.
AB  - The amorphous solid dispersion (ASD) technique has been employed to formulate
      poorly-soluble drugs, however, development of solid dosage forms with ASD is
      challenging due to the high propensity of amorphous drug to precipitate upon
      dissolution. Thus this work aimed to explore the potential of controlled release
      amorphous solid dispersion (CRASD) systems using polyvinyl acetate (PVAc) as a
      release-retarding excipient to mitigate the drug precipitation during dissolution
      of poorly water-soluble drugs. A number of solid oral CRASD dosage forms in
      different shapes and structures were prepared to contain spray-dried SD powders
      of a model BCS Class II drug, celecoxib (CEL), polyvinylpyrrolidone (PVP) and
      polyvinyl acetate (PVAc) which was incorporated in varying ways. In vitro
      dissolution tests were performed to investigate the effect of dosage form design
      on the dissolution/recrystallization profiles. The results indicated that despite
      nearly identical formulation compositions, the dissolution/recrystallization
      profiles could be tailored by changing the dosage form design. Matrix-form
      granules demonstrated greatest improvement of solubility appropriate for rapid
      drug release, while membrane-coated beads appeared to have the greatest potential
      for sustained release and thereby the least possibility of precipitation during
      dissolution. These results suggest that appropriate dosage form design of CRASD
      systems is of potential to reduce the problem of precipitation during dissolution
      of poorly soluble drugs.

PMID- 30194981
TI  - Impaired proteostasis during skeletal muscle aging.
AB  - Aging is a complex phenomenon that has detrimental effects on tissue homeostasis.
      The skeletal muscle is one of the earliest tissues to be affected and to manifest
      age-related changes such as functional impairment and the loss of mass. Common to
      these alterations and to most of tissues during aging is the disruption of the
      proteostasis network by detrimental changes in the ubiquitin-proteasomal system
      (UPS) and the autophagy-lysosomal system (ALS). In fact, during aging the
      accumulation of protein aggregates, a process mainly driven by increased levels
      of oxidative stress, has been observed, clearly demonstrating UPS and ALS
      dysregulation. Since the UPS and ALS are the two most important pathways for the
      removal of misfolded and aggregated proteins and also of damaged organelles, we
      provide here an overview on the current knowledge regarding the connection
      between the loss of proteostasis and skeletal muscle functional impairment and
      also how redox regulation can play a role during aging. Therefore, this review
      serves for a better understanding of skeletal muscle aging in regard to the loss
      of proteostasis and how redox regulation can impact its function and maintenance.

PMID- 30194982
TI  - Cerebral White Matter Hyperintensities and Microbleeds in Acute Ischemic Stroke:
      Impact on Recanalization Therapies. A Review of the Literature.
AB  - Cerebral white matter hyperintensities (WMH) and cerebral microbleeds (CMBs) are
      frequently seen on brain imaging acquired for acute ischemic stroke. Given the
      raising use of recanalization therapies - both intravenous and endovascular - the
      interest on the impact of WMH and CMBs on the risk of intracerebral hemorrhage
      and on functional outcome is growing. In this review, we will discuss the
      relevance of WMH and CMBs among patients with an acute ischemic stroke, focusing
      on the implications for recanalization therapies.

PMID- 30194983
TI  - Polyserine repeats promote coiled coil-mediated fibril formation and length
      dependent protein aggregation.
AB  - Short polyserine (polyS) repeats are frequently found in proteins and longer ones
      are produced in neurological disorders such as Huntington disease (HD) owing to
      translational frameshifting or non-ATG-dependent translation, together with
      polyglutamine (polyQ) and polyalanine (polyA) repeats, forming intracellular
      aggregates. However, the physiological and pathological structures of polyS
      repeats are not clearly understood. Early studies highlighted their structural
      versatility, similar to other homopolymers whose conformation is influenced by
      the surrounding protein context. As polyS stretches are frequently near polyQ and
      polyA repeats, which can be part of coiled coil (CC) structures, and the
      frameshift-derived polyS repeats in HD directly flank CC heptads important for
      aggregation, we investigate here the structural and aggregation properties of
      polyS in the context of CC structures. We have taken advantage of peptide models,
      previously used to study polyQ and polyA in CCs, in which we inserted polyS
      repeats of variable length and studied them in comparison with polyQ and polyA
      peptides. We found that polyS repeats promote CC-mediated polymerization and
      fibrillization as revealed by circular dichroism, chemical crosslinking, and
      atomic force microscopy. Furthermore, they promote CC-based, length-dependent
      intracellular aggregation, which is negligible with 7 and widespread with 49
      serines. These findings show that polyS repeats can participate in the formation
      of CCs, as previously found for polyQ and polyA, conferring to peptides
      distinctive structural properties with aggregation kinetics that are intermediate
      between those of polyA and polyQ CCs, and contribute to an overall structural
      definition of the pathophysiogical roles of homopolymeric repeats in CC
      structures.

PMID- 30194984
TI  - Neurobiological characteristics underlying metabolic differences between males
      and females.
AB  - The hypothalamus is the main integrating center for metabolic control. Our
      understanding of how hypothalamic circuits function to control appetite and
      energy expenditure has increased dramatically in recent years, due to the rapid
      rise in the incidence of obesity and the search for effective treatments.
      Increasing evidence indicates that these treatments will most likely differ
      between males and females. Indeed, sex differences in metabolism have been
      demonstrated at various levels, including in two of the most studied neuronal
      populations involved in metabolic control: the anorexigenic proopiomelanocortin
      neurons and the orexigenic neuropeptide Y/Agouti-related protein neurons. Here we
      review what is known to date regarding the sex differences in these two neuronal
      populations, as well as other neuronal populations involved in metabolic control
      and glial cells.

PMID- 30194985
TI  - Effect of Mineralocorticoid Receptor Antagonists in Individuals With Heart
      Failure With Preserved Ejection Fraction: A Systematic Review.

PMID- 30194987
TI  - Pathogenicity of the homoplasmic C3275T, T4363C and A8343G variant requires
      confirmation.

PMID- 30194986
TI  - Overexpression and RNAi-mediated downregulation of TwIDI regulates triptolide and
      celastrol accumulation in Tripterygium wilfordii.
AB  - The aim of this study was to verify the effects of TwIDI (GenBank: KT279355.1) on
      triptolide and celastrol accumulation in the biosynthesis of terpenoids in
      Tripterygium wilfordii and the regulation of the expression of related genes in
      the triptolide and celastrol biosynthesis pathway. After bioinformatics analysis
      of TwIDI, we cloned the full-length CDS and a specific 398 bp fragment to
      construct overexpression and RNAi vectors, respectively. The specific
      amplification of hygromycin and kanamycin resistance gene fragments confirmed
      that the expression vectors had been successfully delivered into Tripterygium
      wilfordii suspension cells. qRT-PCR was used to detect the expression of TwIDI
      and related genes in the triptolide and celastrol biosynthesis pathway. The
      expression of TwIDI was increased to 157% of the control group (empty vector) in
      the overexpression group, and was reduced to 71% of the control group in the RNAi
      group. Notably, the expression of other genes in the triptolide and celastrol
      biosynthesis pathway also showed differences. For example, TwMCS was reduced to
      62% of the control when TwIDI was overexpressed and increased to 188% in the RNAi
      group. The expression of TwDXS did not change significantly both during TwIDI
      overexpression and RNAi group. The accumulation of triptolide and celastrol in
      the suspension cells of Tripterygium wilfordii was detected by UPLC, revealing
      that the contents of triptolide and celastrol were increased 1.36- and 1.20-fold
      over the control group in the overexpression group, and decreased to 0.16 and
      0.36 of the control group in the RNAi group. Based on these findings, the effect
      on the accumulation of active terpenoids in Tripterygium wilfordii and the
      feedback regulation of genes in the triptolide and celastrol biosynthesis pathway
      was verified through TwIDI overexpression and RNAi experiments.

PMID- 30194988
TI  - Paraben exposures and asthma-related outcomes among children from the US general
      population.
AB  - BACKGROUND: Parabens are synthetic preservatives present in many consumer
      products. Their antimicrobial and endocrine-disrupting properties have raised
      concerns that they might play a role in respiratory and allergic diseases;
      however, studies exploring these associations are scarce. OBJECTIVE: We examined
      the cross-sectional association between parabens and asthma morbidity among 450
      children with asthma and with asthma prevalence among 4023 children in the US
      general population participating in the National Health and Nutrition Examination
      Survey (2005-2014). METHODS: We conducted multivariable logistic regression to
      examine associations between urinary paraben biomarker concentrations (butyl
      paraben, ethyl paraben, methyl paraben [MP], and propyl paraben [PP]) and asthma
      attacks and emergency department visits among children with asthma and with a
      current asthma diagnosis among all children. We also examined heterogeneity of
      associations by sex. RESULTS: We observed an increased prevalence odds of
      reporting emergency department visits for every 10-fold increase in MP and PP
      concentrations among boys with asthma (adjusted prevalence odds ratio, 2.61 [95%
      CI, 1.40-4.85] and 2.18 [95% CI, 1.22-3.89, respectively; Pinteraction-MP = .002
      and Pinteraction-PP = .003); associations remained after adjusting for other
      phenolic compounds previously linked to respiratory outcomes. No other dimorphic
      effects of exposure by sex were observed. Among children in the general
      population, no overall associations with current asthma were observed, although
      there was a positive trend with PP and a current asthma diagnosis. CONCLUSION: We
      identified differential effects of exposure to select parabens by sex on asthma
      morbidity. Further studies are needed to replicate these findings and elucidate
      mechanisms by which parabens could affect respiratory health and elicit dimorphic
      effects by sex.

PMID- 30194989
TI  - Consensus approach for the management of severe combined immune deficiency caused
      by adenosine deaminase deficiency.
AB  - Inherited defects in adenosine deaminase (ADA) cause a subtype of severe combined
      immunodeficiency (SCID) known as severe combined immune deficiency caused by
      adenosine deaminase defects (ADA-SCID). Most affected infants can receive a
      diagnosis while still asymptomatic by using an SCID newborn screening test,
      allowing early initiation of therapy. We review the evidence currently available
      and propose a consensus management strategy. In addition to treatment of the
      immune deficiency seen in patients with ADA-SCID, patients should be followed for
      specific noninfectious respiratory, neurological, and biochemical complications
      associated with ADA deficiency. All patients should initially receive enzyme
      replacement therapy (ERT), followed by definitive treatment with either of 2
      equal first-line options. If an HLA-matched sibling donor or HLA-matched family
      donor is available, allogeneic hematopoietic stem cell transplantation (HSCT)
      should be pursued. The excellent safety and efficacy observed in more than 100
      patients with ADA-SCID who received gammaretrovirus- or lentivirus-mediated
      autologous hematopoietic stem cell gene therapy (HSC-GT) since 2000 now positions
      HSC-GT as an equal alternative. If HLA-matched sibling donor/HLA-matched family
      donor HSCT or HSC-GT are not available or have failed, ERT can be continued or
      reinstituted, and HSCT with alternative donors should be considered. The outcomes
      of novel HSCT, ERT, and HSC-GT strategies should be evaluated prospectively in
      "real-life" conditions to further inform these management guidelines.

PMID- 30194990
TI  - Ras homolog family member A/Rho-associated protein kinase 1 signaling modulates
      lineage commitment of mesenchymal stem cells in asthmatic patients through
      lymphoid enhancer-binding factor 1.
AB  - BACKGROUND: Numbers of mesenchymal stem cells (MSCs) are increased in the airways
      after allergen challenge. Ras homolog family member A (RhoA)/Rho-associated
      protein kinase 1 (ROCK) signaling is critical in determining the lineage fate of
      MSCs in tissue repair/remodeling. OBJECTIVES: We sought to investigate the role
      of RhoA/ROCK signaling in lineage commitment of MSCs during allergen-induced
      airway remodeling and delineate the underlying mechanisms. METHODS: Active RhoA
      expression in lung tissues of asthmatic patients and its role in cockroach
      allergen-induced airway inflammation and remodeling were investigated. RhoA/ROCK
      signaling-mediated MSC lineage commitment was assessed in an asthma mouse model
      by using MSC lineage tracing mice (nestin-Cre; ROSA26-EYFP). The role of
      RhoA/ROCK in MSC lineage commitment was also examined by using MSCs expressing
      constitutively active RhoA (RhoA-L63) or dominant negative RhoA (RhoA-N19).
      Downstream RhoA-regulated genes were identified by using the Stem Cell Signaling
      Array. RESULTS: Lung tissues from asthmatic mice showed increased expression of
      active RhoA when compared with those from control mice. Inhibition of RhoA/ROCK
      signaling with fasudil, a RhoA/ROCK inhibitor, reversed established cockroach
      allergen-induced airway inflammation and remodeling, as assessed based on greater
      collagen deposition/fibrosis. Furthermore, fasudil inhibited MSC differentiation
      into fibroblasts/myofibroblasts but promoted MSC differentiation into epithelial
      cells in asthmatic nestin-Cre; ROSA26-EYFP mice. Consistently, expression of RhoA
      L63 facilitated differentiation of MSCs into fibroblasts/myofibroblasts, whereas
      expression of RhoA-19 switched the differentiation toward epithelial cells. The
      gene array identified the Wnt signaling effector lymphoid enhancer-binding factor
      1 (Lef1) as the most upregulated gene in RhoA-L63-transfected MSCs. Knockdown of
      Lef1 induced MSC differentiation away from fibroblasts/myofibroblasts but toward
      epithelial cells. CONCLUSIONS: These findings uncover a previously unrecognized
      role of RhoA/ROCK signaling in MSC-involved airway repair/remodeling in the
      setting of asthma.

PMID- 30194991
TI  - Acute respiratory infections in early childhood and risk of asthma at age 7
      years.

PMID- 30194992
TI  - Dupilumab progressively improves systemic and cutaneous abnormalities in patients
      with atopic dermatitis.
AB  - BACKGROUND: Dupilumab is an IL-4 receptor alpha mAb inhibiting signaling of IL-4
      and IL-13, key drivers of type 2-driven inflammation, as demonstrated by its
      efficacy in patients with atopic/allergic diseases. OBJECTIVE: This placebo
      controlled, double-blind trial (NCT01979016) evaluated the efficacy, safety, and
      effects of dupilumab on molecular/cellular lesional and nonlesional skin
      phenotypes and systemic type 2 biomarkers of patients with moderate-to-severe
      atopic dermatitis (AD). METHODS: Skin biopsy specimens and blood were evaluated
      from 54 patients randomized 1:1 to weekly subcutaneous doses of 200 mg of
      dupilumab or placebo for 16 weeks. RESULTS: Dupilumab (vs placebo) significantly
      improved clinical signs and symptoms of AD, was well tolerated, and progressively
      shifted the lesional transcriptome toward a nonlesional phenotype (weeks 4-16).
      Mean improvements in a meta-analysis-derived AD transcriptome (genes
      differentially expressed between lesional and nonlesional skin) were 68.8% and
      110.8% with dupilumab and -10.5% and 55.0% with placebo (weeks 4 and 16,
      respectively; P < .001). Dupilumab significantly reduced expression of genes
      involved in type 2 inflammation (IL13, IL31, CCL17, CCL18, and CCL26), epidermal
      hyperplasia (keratin 16 [K16] and MKi67), T cells, dendritic cells (ICOS, CD11c,
      and CTLA4), and TH17/TH22 activity (IL17A, IL-22, and S100As) and concurrently
      increased expression of epidermal differentiation, barrier, and lipid metabolism
      genes (filaggrin [FLG], loricrin [LOR], claudins, and ELOVL3). Dupilumab reduced
      lesional epidermal thickness versus placebo (week 4, P = .001; week 16, P =
      .0002). Improvements in clinical and histologic measures correlated significantly
      with modulation of gene expression. Dupilumab also significantly suppressed type
      2 serum biomarkers, including CCL17, CCL18, periostin, and total and allergen
      specific IgEs. CONCLUSION: Dupilumab-mediated inhibition of IL-4/IL-13 signaling
      through IL-4 receptor alpha blockade significantly and progressively improved
      disease activity, suppressed cellular/molecular cutaneous markers of inflammation
      and systemic measures of type 2 inflammation, and reversed AD-associated
      epidermal abnormalities.

PMID- 30194993
TI  - Hydrops and fetal hypoplastic left heart: An unexpected improvement after
      cessation of maternal polysubstance abuse.

PMID- 30194994
TI  - Lyophilized acai pulp (Euterpe oleracea Mart) attenuates colitis-associated colon
      carcinogenesis while its main anthocyanin has the potential to affect the
      motility of colon cancer cells.
AB  - This study evaluated the possible protective effects of lyophilized acai pulp
      (AP) in a colitis-associated carcinogenesis (CAC) rat model and the modifying
      effect of cyanidin 3-rutinoside (C3R) on the motility of RKO colon adenocarcinoma
      cells, using the wound healing assay. Male Wistar rats were induced to develop
      CAC using 1,2-dimethylhydrazine (DMH) and 2,4,6-trinitrobenzene acid (TNBS).
      Animals were randomly assigned to different groups that received basal diet or
      basal diet supplemented with 5.0% or 7.5% lyophilized AP. The findings indicate:
      1) C3R (25 MUM) has the potential to reduce RKO cell motility in vitro; 2)
      ingestion of lyophilized AP reduces the total number of aberrant crypt foci
      (ACF), ACF multiplicity, tumor cell proliferation and incidence of tumors with
      high grade dysplasia; 3) AP increases the gene expression of negative regulators
      of cell proliferation such as Dlc1 and Akt3, as well as inflammation (Ppara).
      Thus, lyophilized AP could exert a potential antitumor activity.

PMID- 30194995
TI  - Smoked fish products available in European markets: Human exposure to
      polybrominated diphenyl ethers and their metabolites.
AB  - Food safety is continuously threatened by numerous contaminants including those
      originated from environmental pollution, such as PolyBrominated Diphenyl Ethers
      (PBDEs). In the present study, PBDEs and their biologically active metabolites -
      the methoxylated PBDEs (MeO-PBDEs) - were determined in several smoked seafood
      products (N = 30) acquired in the European market. The analyses were performed by
      an environmental-friendly method comprising a "Quick, Easy, Cheap, Effective,
      Rugged, and Safe" (QuEChERS)-based extraction followed by gas chromatography
      (tandem) mass spectrometry. At least one congener of each class of these flame
      retardants were detected in 80% of the samples assessed herein. Whenever above
      the limits of quantification, total PBDEs ranged from 0.21 to 64.49 MUg kg-1,
      while MeO-PBDEs varied between 1.14 and 163.48 MUg kg-1, on a wet weight basis.
      All smoked cod liver samples presented the highest degree of contamination, where
      a 100 g portion represented 12% of the PBDEs provisional tolerable weekly intake,
      as defined by the European food safety authority. Additionally, all tolerable
      daily intake percentages were below 0.2%, thus indicating no cause for concern
      for individuals exposed to PBDEs through consumption of smoked seafood products.
      Finally, multivariate partial least squares regression clarified the relationship
      between product characteristics and instrumental data, allowing to understand
      which variables caused greater influence on the contamination level of smoked
      products.

PMID- 30194997
TI  - Novel insights and innovations in biotechnology towards improved quality of life.
AB  - Resolution of old problems with new tools seems to be a new way of challenging
      and finding the keys to innovation. A holistic view of different branches of
      science and industry, including services for society, is critically important for
      the development of modern science. The International Congress Eurobiotech 2017
      was a special opportunity for such a universal view. In this paper, we discuss
      the application of different small RNAs, stem cells, epigenetics and sequencing,
      as well as art and bioeconomy. Our most significant message is not a new one but
      is very universal: biotechnology is vital for society.

PMID- 30194996
TI  - RIFM fragrance ingredient safety assessment, ethyl isobutyrate, CAS Registry
      Number 97-62-1.

PMID- 30194998
TI  - Purification and characterization of exopolysaccharide produced by Weissella
      cibaria YB-1 from pickle Chinese cabbage.
AB  - An exopolysaccharide (EPS) was produced by Weissella cibaria YB-1 isolated from
      pickle Chinese cabbage. The EPS was purified and characterized. The
      monosaccharide composition of the EPS was glucose, and its molecular mass was
      3.89 * 106 Da, as determined by gas chromatography (GC) and high performance
      liquid chromatography (HPLC). The structural characterization of purified EPS
      determined by Fourier transform infrared (FT-IR) spectra and nuclear magnetic
      resonance (NMR) spectra demonstrated that W. cibaria YB-1 synthesized a linear
      dextran that predominately had alpha-(1 -> 6) glycosidic linkages with only a few
      alpha-(1 -> 3) (4.3%) linked branches. The water solubility index (WSI), water
      holding capacity (WHC) and emulsifying activity (EA) of YB-1 dextran were 95.23
      +/- 4.45, 287.84 +/- 16.23 and 84.43 +/- 3.65%, respectively. The in-vitro
      antioxidant activities of the dextran showed good scavenging effects on
      superoxide anion radical and hydroxyl radical.

PMID- 30194999
TI  - Application of chitosan as biocompatible polysaccharide in quantification of some
      benzodiazepines affecting sleep disorders: A new platform for preparation of
      bioactive scaffolds.
AB  - Herein, a reusable and time-saving strategy for the electrochemical
      polymerization of dopamine (EPD) in the presence of chitosan is reported. In this
      work, biocompatible polymer chitosan (CS) was electrodeposited on the surface of
      PDA modified glassy carbon electrode using layer-by-layer strategy. Owing to the
      abundant catechol and amine groups in the PDA layer, uniform gold nanoparticles
      (Au NPs) are deposited onto the POLY(DA-CS) and can effectively prevent the
      recombination of electron-hole pairs generated from photo-electrocatalysis and
      transfer the captured electrons to participate in the electrocatalytic reaction
      process. Compared with POLY(DA-CS), the as-prepared POLY(DA-CS)-AuNPs organic
      inorganic hybrid exhibit electrochemical sensitivity for the detection of some
      benzodiazepines and display excellent durability. Furthermore, the mussel
      inspired electropolymerization strategy and the fast EPD-Au nanoparticle
      decorating process presented herein can be readily extended to various biomedical
      and pharmaceutical analysis. It is the adaptation of the established POLY(DA-CS)
      Au NPs organic-inorganic hybrid for a selective, robust, and generalizable
      sensing system that is the emphasis of this work.

PMID- 30195000
TI  - Characterization, in vitro binding properties, and inhibitory activity on
      pancreatic lipase of beta-glucans from different Qingke (Tibetan hulless barley)
      cultivars.
AB  - In order to explore Qingke beta-glucans as functional food ingredients for
      prevention of obesity, the physicochemical structures, in vitro binding
      properties, and inhibitory activities on pancreatic lipase of beta-glucans from
      three different Qingke cultivars, including Ganyucang (black), Dingqing (blue),
      and Zangqing 320 (white), were investigated and compared. Results showed that
      molecular weights, particle sizes, and intrinsic viscosities of beta-glucans from
      colored (black and blue) Qingke cultivars were much higher than those of white
      Qingke beta-glucans, respectively. In addition, the constituent monosaccharides
      of beta-glucans from colored Qingke cultivars were determined as arabinose,
      xylose, glucose, and galactose, and glucose was the dominant monosaccharide.
      Furthermore, colored Qingke beta-glucans exerted strong fat binding, cholesterol
      binding, and bile-acid binding capacities, as well as inhibitory activities on
      pancreatic lipase, which were much higher than those of white Qingke beta
      glucans. Indeed, the fat binding, cholesterol binding, and bile-acid binding
      capacities, as well as the inhibitory activities on pancreatic lipase of Qingke
      beta-glucans were positively associated with their molecular weights and
      intrinsic viscosities. Results are beneficial for better understanding of the
      structure-function relationship of Qingke beta-glucans, and beta-glucans from
      colored Qingke cultivars (Ganyucang and Dingqing) could be further explored as
      functional food ingredients for prevention of obesity.

PMID- 30195001
TI  - Isolation and functional characterization of two thioredoxin h isoforms from
      grape.
AB  - Thioredoxins (Trxs) are small ubiquitous proteins that participate in dithiol
      disulfide exchange reactions. In contrast to animals and prokaryotes, plants
      possess different types of Trxs that play a vital role in a number of different
      cellular processes. Two full-length cDNAs encoding different Trx h isoforms,
      designated VvTrx h2 and VvTrx h3, were isolated and cloned from grape (Vitis
      vinifera L. cv. Askari) berry tissue by rapid amplification of cDNA ends (RACE)
      method. VvTrx h2 and VvTrx h3 were heterologously expressed in Escherichia coli
      and their activities were compared using DTT-dependent insulin reduction and 5,5'
      dithio-bis (2-nitrobenzoic acid) (DTNB) reduction activities. The NADPH-dependent
      DTNB reduction assay demonstrated that the both VvTrx h isoforms were reduced by
      NADPH-dependent thioredoxin reductase (NTR) from E. coli. Under heat shock
      treatment, the recombinant VvTrx h proteins formed the oligomeric structures at
      above 50  degrees C with a decrease in their disulfide reductase activities. The
      redox-dependent structural changes of VvTrx h2 and VvTrx h3 revealed that their
      oligomeric structures were changed into monomers and significantly increased
      their disulfide reductase activities. Furthermore, the both recombinant proteins
      were able to conserve a DTNB reduction activity even after 15 min heating at 99 
      degrees C.

PMID- 30195002
TI  - Ultrasensitive immunoassay of tumor protein CA 15.3 in MCF-7 breast cancer cell
      lysates and unprocessed human plasma using gold nanoparticles doped on the
      structure of mesoporous silica.
AB  - Breast cancer is the most common threat in women worldwide. Increasing death rate
      of diagnosed cases is the main leading cause of designing specific immunoassay
      for tumor marker in breast cancer. Cancer antigen 15-3 (CA 15-3) is a tumor
      protein for many types of cancer, most notably breast cancer. Herein, we report a
      sandwich-type electrochemical immunosensor based on signal amplification strategy
      of multiple nanocomposites to detection of CA 15-3 biomarker. The proposed
      immunosensor fabricated by reduced graphene oxide (rGO), poly-dopamine (PDA) and
      amino functionalized mesoporous silica (MCM-41-NH2) doped by gold nanoparticles
      composite on the glassy carbon electrode with a large surface area which was
      prepared a new platform to immobilization of primary antibodies and provide
      excellent conductivity. To further amplify the electrochemical signal, the trace
      tag on the foundation of gold nanoparticles (AuNPs) is coated with MCM-41-NH2
      nanocomposite through thionine linking, which provides more amino groups to
      capture more horseradish peroxidase-labeled antibodies (HPR-Ab2) and enhances the
      conductivity. Under optimal conditions, the developed immunosensor exhibits
      excellent analytical performance for the determination of CA 15-3 with a wide
      linear range from 0.002 to 125 U/mL and a low limit of quantification of 0.002
      U/mL. Furthermore, satisfactory results are obtained for the determination of CA
      15-3 in human plasma samples, indicating the potential of the immunoassay to be
      applied in clinical analysis.

PMID- 30195003
TI  - Engineering the affinity of a family 11 carbohydrate binding module to improve
      binding of branched over unbranched polysaccharides.
AB  - Carbohydrate binding modules (CBMs) are non-catalytic domains within larger
      multidomain polypeptides. The CelH from Ruminoclostridium (Clostridium)
      thermocellum contains a family 11 CBM (RtCBM11) with high binding affinity for
      the linear polysaccharide beta-glucan, and low affinity for the branched
      xyloglucan. Screening a random RtCBM11 mutant phage library created by error
      prone PCR for xyloglucan binding identified RtCBM11 mutants with enhanced
      xyloglucan affinity. Subsequent recombination of the selected variants by site
      directed mutagenesis generated the H102L/Y152F and Y46N/G52D/H102L/Y152F mutants.
      Fusion of the quadruple RtCBM11 mutant with the xyloglucanase from Aspergillus
      niveus increased the catalytic efficiency of the enzyme by 38%. Isothermal
      titration calorimetry demonstrated increased xyloglucan affinity for both mutants
      and reduced affinity for beta-glucan in the H102L/Y152F mutant. Molecular
      dynamics simulations indicated that the increased xyloglucan specificity results
      both from formation of a xylosyl binding pocket in the carbohydrate binding
      cleft, and via modulation of a hydrogen bond network between the oligosaccharide
      ligand and the protein. These results explain the improved xyloglucan binding in
      the RtCBM11 H102L/Y152F mutant and advance the understanding of the structural
      determinants of CBMs binding that discriminate between branched and unbranched
      polysaccharides.

PMID- 30195004
TI  - Preparation and stability of nano-scaled gel beads of lambda-carrageenan bound
      with ferric ions.
AB  - Iron-deficiency anemia (IDA) is a major global public health problem, and the
      iron fortifiers in diet are clearly needed in the prevention and improvement of
      IDA for humans. A novel nano-scaled gel beads of lambda-carrageenan (lambda-car)
      specifically binding with ferric ions was developed to be a promising iron
      fortifier with no adverse organoleptic changes on food. Turbidity measurement,
      thermogravimetric analysis and Fourier transform infrared spectroscopy confirmed
      the successful chelating. The gel beads of lambda-car-Fe3+ complex showed good
      dispersibility and solvent stability. The in vitro cell viability of HepG2 cells
      treated with lambda-car-Fe3+ was over 75% at 5 mg/mL of ferric ions, indicating a
      significant cytotoxicity reduction of ferric ions. The stability of lambda-car
      Fe3+ complex powder was obviously increased against browning during 60 d storage
      with zein coating, which was attributed to the prevention of moisture permeation.
      Zein coated gel beads also performed a slow release of ferric ions in simulated
      gastrointestinal juices, resulting from the compact and hydrophobic zein surface
      delaying the dissociation of lambda-car-Fe3+ in acidic environment. This lambda
      car-Fe3+ complex would have a great potential as a safe iron fortifier and
      facilitate iron supplementary with the advantage to relieve the side effects of
      iron ions.

PMID- 30195005
TI  - Purification and characterization of a novel protease-resistant GH27 alpha
      galactosidase from Hericium erinaceus.
AB  - A novel 57-kDa acidic alpha-galactosidase designated as HEG has been purified
      from the dry fruiting bodies of Hericium erinaceus. The isolation protocol
      involved ion-exchange chromatography and gel filtration on a Superdex75 column.
      The purification fold and specific activity were 1251 and 46 units/mg,
      respectively. A BLAST search of internal peptide sequences obtained by liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) analysis suggested that the
      enzyme belonged to the GH27 family. The activity of the enzyme reached its
      maximum at a pH of 6.0 or at 60  degrees C. The enzyme was stable within an
      acidic pH range of 2.2-7.0 and in a narrow temperature range. The enzyme was
      strongly inhibited by Zn2+, Fe3+, Ag+ ions and SDS. The Lineweaver-Burk plot
      suggested that the mode of inhibition by galactose and melibiose were of a mixed
      type. N-bromosuccinimide drastically decreased the activity of the enzyme,
      whereas diethylpyrocarbonate and carbodiimide strengthened the activity slightly.
      Moreover, the isolated enzyme displayed remarkable resistance to acid proteases,
      neutral proteases and pepsin. The enzyme could also hydrolyse oligosaccharides
      and polysaccharides. In addition, acidic protease promoted the hydrolysis of RFOs
      by HEG. The Km values of the enzyme towards pNPGal, raffinose and stachyose were
      0.36 mM, 40.07 mM and 54.71 mM, respectively. These favourable properties
      increase the potential of the enzyme in the food industry and animal feed
      applications.

PMID- 30195006
TI  - Tick-borne pathogens in removed ticks Veneto, northeastern Italy: A cross
      sectional investigation.
AB  - BACKGROUND: In Italy, the incidence of tick-borne diseases in humans is
      underestimated, as they are not obligatorily notifiable. The aim of this study
      was to investigate the presence of tick-borne pathogens in ticks removed from
      human subjects in Veneto region (northeastern Italy), an area for which no
      published studies are yet available. METHOD: Forty-five ticks prospectively
      removed from human subjects, between March and August 2016, were analysed for
      bacterial DNA. RESULTS: Seven of 45 ticks were infected with bacteria, including
      human pathogens: 4 Rickettsia spp. (9%), including R. monacensis and R.
      helvetica; 3 Borrelia spp. and 1 Anaplasma phagocytophilum. Three subjects bitten
      by infected ticks reported symptoms. CONCLUSIONS: Rickettsiosis and anaplasmosis,
      tick-borne diseases previously not considered in northeastern Italy, should not
      be neglected. A new survey for a longer period is required to obtain stronger
      epidemiological data.

PMID- 30195007
TI  - The use of medical alert jewelry to communicate allergy information.

PMID- 30195008
TI  - Recall urticaria-A new clinical sign in the diagnosis of alpha-gal syndrome.

PMID- 30195009
TI  - Engineering a spermidine biosynthetic pathway in Clostridium thermocellum results
      in increased resistance to furans and increased ethanol production.
AB  - Polyamines are low molecular weight aliphatic nitrogen compounds found
      ubiquitously in microorganisms, plants, and animals. Spermidine is a common
      polyamine that plays a role in stabilizing chromatin, DNA replication,
      transcription, translation, as well as the regulation of cell growth and
      apoptosis in eukaryotes. Amines are also associated with defense to a number of
      environmental stresses including elevated temperature and have been shown to be
      involved in tolerance to fermentation inhibitors such as furan derivatives and
      acetic acid in Saccharomyces cerevisiae. While the tolerance and detoxifying
      mechanisms have been intensively studied, metabolic engineering efforts to
      construct tolerant and resistant strains have been few. Here we show that
      exogenously added spermidine confers enhanced tolerance to furans and acetic acid
      in the Gram-positive bacterium, Clostridium thermocellum. Deletion of the
      endogenous spermidine synthase resulted in a severe growth defect and
      hypersensitivity to both furans and acetic acid. Exogenously added spermidine
      rescued all three phenotypes. Overexpression of the endogenous spermidine
      synthase resulted in increased tolerance to these compounds without added
      spermidine. Increased tolerance to these fermentation inhibitors will facilitate
      the use of C. thermocellum, one of the most cellulolytic of all known bacterial
      species, for the production of fuels from plant biomass substrates.

PMID- 30195010
TI  - Pathologic Specimens at Time of Pyeloplasty: Frequency and Practice Patterns.
AB  - OBJECTIVE: To assess national and regional practice patterns and rates of
      pathologic specimen identification sent at time of pyeloplasty, as well as
      project associated costs, we used a national administrative database. The rate at
      which the excised ureteropelvic junction obstruction (UPJO) is sent for
      pathologic identification is variable, arguably without a clear clinical purpose.
      MATERIALS / METHODS: Utilizing a national administrative database of privately
      insured patients, 1496 individual cases were identified using international
      classification of diseases (ICD) and Current Procedural Terminology (CPT) coding.
      Patients from 0-18 years of age were included whose pyeloplasty was performed
      during 2010-2014. Patients who were and were not billed for pathologic
      identification at time of surgery were identified. Regional practice patterns and
      associated costs were determined. RESULTS: One thousand four hundred and ninety
      six pyeloplasty cases were identified (68.2% males). Specimens were sent for
      pathologic identification in 827 cases (55%). Average age was 5.8 years for those
      without pathology and 4.6 years for those in whom a specimen was billed.
      Regionally, the Western United States was least likely to bill for surgical
      pathology (49%). The parental out-of-pocket payment for the encounter was on
      average $1518 for cases in which pathology was sent and $1398 for those cases for
      which no pathology bill was identified. CONCLUSION: Pediatric pyeloplasty is a
      common surgical procedure for which a pathologic specimen is sent in as many as
      55% of cases in this cohort. Regional differences exist across the country and
      there is an associated slightly higher out-of-pocket cost in cases for which
      pathologic specimens are sent at time of pyeloplasty.

PMID- 30195011
TI  - Understanding the Popcorn Effect During Holmium Laser Lithotripsy for Dusting.
AB  - OBJECTIVE: To assess low and high power settings for the popcorn technique, and
      relationship of laser fiber-to-stone distance and calyceal size on submillimeter
      fragmentation. Our in vitro findings may help guide strategies to improve a
      dusting technique for ureteroscopy. METHODS: BegoStones were fragmented in small
      (127 mm3) and large (411 mm3) sized bulbs to simulate calyces, using a 120 W
      Ho:YAG laser. A 242 MUm fiber was introduced through a ureteroscope mounted to a
      3D positioner with its tip located at 0 or 2 mm distance from the stones. 20 W [1
      J * 20 Hz, 0.5 J * 40 Hz] and 40 W [1 J * 40 Hz, 0.5 J * 80 Hz] settings were
      assessed, including short pulse and long pulse modes. Total energy delivered was
      constant at 7.2 kJ. Primary outcome was percentage of stone mass converted to
      fragments <1 mm. High-speed imaging was performed to study stone movement and/or
      fragmentation. RESULTS: For all settings, popcorn lithotripsy yielded more
      submillimeter fragments when performed with the fiber positioned on the stone
      compared to 2 mm from the stone (P <.05). Distribution of submillimeter fragments
      was higher when utilizing high frequencies regardless of pulse energy. At 2 mm
      distance, popcorning was more effective in the small model (P <.05). At 2 mm
      distance, short pulse was superior to long pulse. Video analysis showed
      fragmentation did not occur when stones collided with each other. At 80 Hz/2 mm
      distance, only 17.5% of pulses impacted fragments. CONCLUSION: Popcorn technique
      is more effective when the fiber is directly in contact with stone, and when
      performed in a small calyceal model. Utilizing settings with higher frequencies
      may improve dusting outcomes.

PMID- 30195012
TI  - Single Session Bilateral Vs Staged Bilateral Ureteroscopy for Nephrolithiasis: An
      Assessment of Safety and Efficacy.
AB  - OBJECTIVE: To compare outcomes of patients undergoing single session bilateral
      ureteroscopy (SSBU) to those undergoing planned staged ureteroscopy (URS) for
      bilateral nephrolithiasis. While SSBU has the advantage of 1 anesthetic
      procedure, some may pursue a staged approach due to the potential higher risk of
      complications and patient discomfort with 2 ureteral stents. METHODS: We
      retrospectively identified patients undergoing SSBU and planned staged URS for
      nephrolithiasis between December 2007 and December 2014. Preoperative
      characteristics, intraoperative techniques, and postoperative outcomes were
      compared. Stone burden was calculated as cumulative stone diameter. Residual
      stone fragments were defined as any stone visible on postoperative imaging.
      RESULTS: Sixty-three patients underwent SSBU and 37 underwent planned staged URS.
      Both cohorts had a relatively large cumulative stone burden (30.9 mm vs 32.4 mm,
      P = .71). Total operative time was significantly longer for planned staged URS
      (139 vs 86 minutes, P <.0001). There were no significant differences in
      complications or emergency room visits between the 2 cohorts despite bilateral
      ureteral stents being placed in the majority of the SSBU cohort (73%). There were
      no differences in stone-free rates or the need for additional procedures.
      CONCLUSION: SSBU is safe and effective with overall shorter operative times and
      similar stone-free rates compared to planned staged URS. Bilateral ureteral stent
      placement did not increase the rate of unplanned emergency visits. For patients
      with bilateral nephrolithiasis, urologists should strongly consider SSBU to limit
      anesthetic exposure, overall operative time, and health care costs.

PMID- 30195013
TI  - Anaphylactoid Reactions After Instillation of Contrast Material Into the Urinary
      Tract: A Survey of Contemporary Practice Patterns and Review of the Literature.
AB  - OBJECTIVE: To assess drug reactions (ADRs) encountered by practicing urologists
      for contrast instilled into the urinary collecting system, and to describe
      current practice patterns regarding contrast administration into the urinary
      tract for patients with known contrast allergies. METHODS: Endourological Society
      members were e-mailed a web-based survey about their prior experience with
      contrast-related ADRs and practices for contrast administration into the urinary
      tract among patients with known intravenous contrast allergies. Chi-squared
      analysis was used to compare management patterns between patients with
      established allergies and those without. RESULTS: An estimated 2300-2500 e-mails
      were reached, resulting in an estimated response rate of 6.3%-8%. Over 75% of
      respondents were fellowship trained. Average time in practice was 16 years, and
      respondents performed a mean of 6.7 urologic contrast studies per week. Among
      respondents, 32.6%, 14.7%, and 4.0% had treated at least 1 patient with a mild,
      moderate, or severe reaction, respectively. Contrast-related ADRs were most
      commonly associated with retrograde pyelogram (50%). For patients with known
      contrast allergies, 5.4% pursue additional work-up before administering contrast
      in the urinary tract. Pretreatment with antihistamine or steroids is used by
      24.8% and 23.4%, respectively. When performing retrograde pyelograms for such
      patients, urologists are more likely to use dilute contrast (P = .003), but
      otherwise do not significantly alter technique. CONCLUSION: Contrast ADRs are
      encountered not infrequently among practicing urologists. There is notable
      practice variation in the management of patients with known contrast allergies,
      though the overall perceived risk of contrast use in these patients is low,
      provided good technique is used.

PMID- 30195014
TI  - Detection and Treatment of Primary Prostatic Melanoma.
AB  - OBJECTIVE: To describe a case of primary melanoma of the prostate gland, then
      review the published literature of similar cases. METHODS: Presentation of the
      clinical course of a 42-year-old man diagnosed with primary melanoma of the
      prostate after presenting with gross hematuria. Review of published literature.
      RESULTS: Primary melanoma of the genitourinary tract is a very rare disease,
      representing less than 1% of all melanomas in men. Only 6 cases of primary
      melanomas have been previously reported in the English literature. CONCLUSION:
      The current report emphasizes the importance of a multidisciplinary approach and
      adherence to treatment principles in cutaneous melanoma. With complete surgical
      extirpation (including extended pelvic lymphadenectomy as needed), close
      surveillance using 18F-FDG PET/CT, and aggressive systemic treatment in patients
      with good performance status, cure can be achieved.

PMID- 30195015
TI  - Functional characterization of the GABA transporter GAT-1 from the deep-sea
      mussel Bathymodiolus septemdierum.
AB  - Mammalian gamma-aminobutyric acid (GABA) transporter subtype 1 (GAT-1) is a
      specific transporter for GABA, an inhibitory neurotransmitter in GABA-ergic
      neurons. GAT-1 belongs to the GAT group, in which five related transporters, GAT
      2, GAT-3, GAT-4, CT1, and TAUT are known in mammals. By contrast, the deep-sea
      mussel, Bathymodiolus septemdierum has only two GAT group members, BsGAT-1 and
      BsTAUT, and their function in environmental adaptation is of interest to better
      understand the physiology of deep-sea organisms. Compared with BsTAUT, the
      function of BsGAT-1 is unknown. Here, we report the functional characterization
      of BsGAT-1. Analyses of BsGAT-1 expressed in Xenopus oocytes showed that it could
      transport GABA in a Na+- and Cl--dependent manner, with Km and Vmax values of
      0.58 MUM and 1.97 pmol/oocyte/h, respectively. BsGAT-1 activity was blocked by
      the GAT-1 selective inhibitors SKF89976A and ACHC. Competition assays indicated
      that BsGAT-1 has no affinity for taurine and thiotaurine. These characteristics
      were common with those of mammalian GAT-1, suggesting its conserved function in
      the nervous system. However, BsGAT-1 showed a certain affinity for hypotaurine,
      which is involved in sulfide detoxification in hydrothermal vent-specific
      animals. This result suggests an additional role for BsGAT-1 in sulfide
      detoxification, which may be specific to the deep-sea mussel. In a tissue
      distribution analysis, BsGAT-1 mRNA expression was observed in various tissues.
      The expression in the adductor and byssus retractor muscles, labial palp, and
      foot, which possibly contain ganglia, suggested a function in the neural system,
      while BsGAT-1 expression in other tissues might be related to sulfide
      detoxification.

PMID- 30195016
TI  - Comment on "establishment of human retinal mitoscriptome gene expression
      signature for diabetic retinopathy using cadaver eyes".
AB  - We read with great interest the article by Gowthaman and colleagues. The study's
      findings are useful for the discovery of biomarker and developing therapeutic
      regimen in diabetic retinopathy. On the other hand, from our perspective, the
      bioinformatics analyses need further context as the statistics for differential
      fold changes in expression data are not explained fully. Due to the high false
      positives caused by a large number of probes and multiple comparisons, it seems
      essential to analyze microarray data properly to reach a reliable result by a
      statistical method. Only selecting genes with >0.6-fold change in expression is
      not reliable and suitable for high-level microarray analysis.

PMID- 30195017
TI  - Inflammatory mediators resulting from transglutaminase 2 expressed in mast cells
      contribute to the development of Parkinson's disease in a mouse model.
AB  - This study aimed to investigate the role of transglutaminase 2 (TG2) expressed in
      mast cells in substantia nigra (SN) in Parkinson's disease (PD) model or human PD
      patients. C57BL/6 mice received 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
      (MPTP) by ip injection to induce PD. Bone marrow-derived mast cells (BMMCs) were
      adoptively transferred to TG2 knockout (KO or TG2-/-) mice by iv injection 1 day
      before MPTP injection or stimulated by 1 methyl-4-phenylpyridinium (MMP+). KO
      MPTP mice showed reduced expression of tyrosine hydroxylase (TH) and dopamine
      (DA) transporter (DAT) and loss of TH+ DA neurons, and expression of markers (c
      kit, tryptase, FcepsilonRI), mediators' release (histamine, leukotrienes,
      cytokines), and TG2 related to mast cells, and co-localization of DA neuronal
      cells and mast cells in SN tissues or release of mediators and TG2 activity in SN
      tissues and sera versus those in WT (wild type)-MPTP or BM + KO-MPTP mice. KO
      MPTP mice reversed the alterations of behavior. KO-BMMCs-transferred KO-MPTP (BM
      + KO-MPTP) mice had restoration of all the responses versus the KO-MPTP mice.
      MPP+-stimulated BMMCs had increased mediators' release, which were inhibited by
      TG2 inhibitor (R2 peptide). All the mediators and TG2 activity were also
      increased in the sera of human PD patients. The data suggest that TG2 expressed
      in mast cells recruited into SN tissues might contribute to neuroinflammation,
      which is known as one of the important features in pathogenesis of PD, via up
      regulating the release of various mediators.

PMID- 30195018
TI  - Schisandrin B exhibits potent anticancer activity in triple negative breast
      cancer by inhibiting STAT3.
AB  - Triple negative breast cancer (TNBC) is an aggressive subgroup of human breast
      cancer. In this study, we have examined the potential of Schisandrin B (Sch B), a
      bioactive chemical compound found in Schisandra chinensis, against TNBC. We used
      MDA-MB-231, BT-549, and MDA-MB-468 TNBC cells and immunodeficient mice to study
      the effect of Sch B. Our results show that Sch B inhibits TNBC growth by inducing
      cell cycle arrest and by triggering apoptotic death. Sch B also inhibited the
      migration and colony formation of tumor cells, and prevented the growth of TNBC
      cells in mice. We found that these inhibitory activities were mediated through
      suppression of signal transducer and activator of transcription-3 (STAT3)
      phosphorylation and nuclear translocation. Taken together, our studies show that
      Sch B has potent anti-tumor activity against TNBC via a novel mechanism involving
      STAT3 inactivation.

PMID- 30195019
TI  - The effects of Nrf2 knockout on regulation of benzene-induced mouse
      hematotoxicity.
AB  - Previous studies have demonstrated that oxidative stress is implicated in benzene
      induced hematotoxicity. However, the low dose-response effects and the mechanism
      underlying perturbation of hematopoiesis remain to be defined. This study aims to
      address the role of Nrf2 pathway in mediating benzene-induced hematotoxicity.
      Nrf2+/+ (wildtype, Nrf2-WT) and Nrf2-/- (knockout, Nrf2-KO) mice were
      administrated with benzene at doses of 0.1, 1.0, 10.0, 100.0 mg/kg by oral gavage
      for a consecutive 4 weeks (6 times/week). As a result, benzene exposure caused a
      decline of WBC and lymphocyte counts in a dose-dependent manner at a dose range
      from 1.0 to 100.0 mg/kg, while low dose benzene induced hormesis effects.
      Interestingly, Nrf2 deficiency seemed to relieve the decline of peripheral blood
      cell counts upon benzene exposure, indicating the involvement of Nrf2 in
      regulation of benzene-induced hematotoxicity. The suppression of phase II enzyme
      expression in Nrf2-KO mice resulted in considerable reduction in detoxification
      indicated by the decrease of urinary S-phenylmercapturic acid (SPMA), a
      metabolite of benzene. Ex vivo assay revealed enhanced cytotoxicity and oxidative
      stress were induced by benzene in Nrf2-KO mice. Notably, the depletion of Nrf2
      triggered the proliferation and differentiation of hematopoietic cells, but
      induced aberrant morphological changes in periphery erythrocytes and bone marrow
      cells, implicating the compensatory effects carried on at the expense of
      induction of dysfunctional blood cells. Our findings provide a new insight into a
      low dose-response towards benzene-induced hematotoxicity and uncover the critical
      role of Nrf2 pathway in mediating abnormal hematopoiesis in response to oxidative
      stress.

PMID- 30195020
TI  - Involvement of orexinergic receptors in the nucleus accumbens, in the effect of
      forced swim stress on the reinstatement of morphine seeking behaviors.
AB  - Orexinergic system is involved in primary rewards; the neural circuit of the
      ventral tegmental area (VTA), nucleus accumbens (NAc), prefrontal cortex and
      amygdala represents overlapping elements mediating the rewarding effects of drugs
      and stressful experiences. The NAc integrates reward-related information from the
      VTA. Also, it has been indicated that orexinergic system activates the mesolimbic
      dopamine projecting neurons to the NAc and promotes the development of reward in
      rodents. Therefore, in the present study, the conditioned place preference (CPP)
      paradigm was used to determine the role of the two types of orexin receptors
      (OXR) in the NAc in forced swim stress (FSS), as physical stress, and/or priming
      induced reinstatement of morphine. The CPP was induced by injecting morphine (5
      mg/kg, SC for 3 days) and lasted for eight free-morphine days; the reinstatement
      was induced by administration of effective priming dose of morphine (1 mg/kg;
      sc). The extinguished rats received intra-NAc injection of SB334867 as OX1R
      antagonist or TCSOX229 as OX2R antagonist before effective priming dose injection
      of morphine (1 mg/kg; sc). In others, the extinguished rats were given intra-NAc
      injection of SB334867 or TCSOX229 and then, they underwent FSS before injection
      of ineffective priming dose of morphine (0.5 mg/kg; sc). Our results showed that
      intra-accumbal administration of SB334867 or TCSOX229 could inhibit morphine
      priming- and FSS-induced reinstatement of extinguished morphine-seeking in the
      rats. It seems that OXR in the NAc may be involved in reward and could play an
      important role in the effect of stress on reinstatement of morphine-seeking
      behaviors in this area.

PMID- 30195021
TI  - Nucleus incertus ablation disrupted conspecific recognition and modified
      immediate early gene expression patterns in 'social brain' circuits of rats.
AB  - Social interaction involves neural activity in prefrontal cortex, septum,
      hippocampus, amygdala and hypothalamus. Notably, these areas all receive
      projections from the nucleus incertus (NI) in the pontine tegmentum. Therefore,
      we investigated the effect of excitotoxic lesions of NI neurons in adult male,
      Wistar rats on performance in a social discrimination test, and associated
      changes in immediate-early gene protein levels. NI was lesioned with quinolinic
      acid, and after recovery, rats underwent two trials in the 3-chamber test. In the
      first trial, NI-lesioned and sham-lesioned rats spent longer exploring a
      conspecific than an inanimate object. By contrast, in the second trial, NI
      lesioned rats visited the familiar and novel conspecific chambers equally,
      whereas sham-lesioned rats spent longer engaging with the novel rat.
      Quantification of Fos- and Egr-1-immunoreactivity (IR) levels in brain areas
      implicated in social behaviour, revealed that social encounter and NI lesion
      produced complex, differential changes. For example, Egr-1-IR was broadly
      decreased in several amygdala nuclei in NI-lesioned rats relative to sham, but
      Fos-IR levels were unaltered. In hippocampus, NI-lesioned rats displayed
      decreased Fos-IR in CA2 and CA3, while Egr-1-IR was increased in the polymorphic
      dentate gyrus, CA1, CA2 and subiculum of NI-lesioned rats, relative to sham.
      Social encounter-related Egr-1-IR was also decreased in septum and anterior and
      lateral hypothalamus of NI-lesioned rats. Overall, these data suggest NI networks
      can modulate the activity of sensory, emotional and executive brain areas
      involved in social recognition, with a likely involvement of neuronal Egr-1
      activation in amygdala, septum and hypothalamus, and Erg-1 inhibition in
      hippocampus.

PMID- 30195022
TI  - Methylene blue exerts rapid neuroprotective effects on lipopolysaccharide-induced
      behavioral deficits in mice.
AB  - Depression is a recurrent neuropsychiatric disorder accompanied with other
      behavioral deficits, including memory impairment. A few studies have shown that
      methylene blue (MB) could promote cortical neurogenesis and exert neuroprotective
      effects on various brain diseases, including bipolar disorder. However, the
      potential antidepressant effects of MB have not been fully investigated. The
      present study was designed to investigate the effects of MB pretreatment on
      behavioral deficits and the underlying mechanisms in a lipopolysaccharide (LPS)
      induced depression mouse model. Mice were given saline (5 mL/kg) or MB (5, 20
      mg/kg) intraperitoneally (i.p.) 30 min prior to lipopolysaccharide (LPS, 800
      MUg/kg, i.p.) or the following behavioral tests. Thereafter, serum heme oxygenase
      1(HO1) were determined by ELISA. The results showed that LPS significantly
      induced body weight loss and behavioral deficits that included increased floating
      time in the forced swimming test, increased immobility time in the tail
      suspension test, decreased sucrose preference in the sucrose preference test, and
      memory impairment in the novel object recognition (all p < 0.05) when compared
      with that of LPS-free mice. MB treatment significantly blocked most of these
      behavioral deficits induced by LPS when compared with that of mice in LPS-exposed
      groups. Furthermore, MB pretreatment prevented the LPS-induced decrease in serum
      level of HO1. These findings suggested that MB exerts rapidly neuroprotective
      effects in an LPS-induced depression mouse model, which may be involved in its
      regulation on the peripheral HO system.

PMID- 30195023
TI  - Melanin-concentrating hormone is a major substance mediating light wavelength
      dependent skin color change in larval zebrafish.
AB  - Melanosome dispersion is important for protecting the internal organs of fish
      against ultraviolet light, especially in transparent larvae with underdeveloped
      skin. Melanosome dispersion leads to dark skin color in dim light. Melanosome
      aggregation, on the other hand, leads to pale skin color in bright light. Both of
      these mechanisms are therefore useful for camouflage. In this study, we
      investigated a hormone thought to be responsible for the light wavelength
      dependent response of melanophores in zebrafish larvae. We irradiated larvae
      using light-emitting diode (LED) lights with peak wavelengths (lambdamax) of 355,
      400, 476, 530, and 590 nm or fluorescent light (FL) 1-4 days post fertilization
      (dpf). Melanosomes in skin melanophores were more dispersed under short
      wavelength light (lambdamax <= 400 nm) than under FL. Conversely, melanosomes
      were more aggregated under mid-long wavelength light (lambdamax >= 476 nm) than
      under FL. In addition, long-term (1-12 dpf) irradiation of 400 nm light increased
      melanophores in the skin, whereas that of 530 nm light decreased them. In
      teleosts, melanin-concentrating hormone (MCH) aggregates melanosomes within
      chromatophores, whereas melanocyte-stimulating hormone, derived from
      proopiomelanocortin (POMC), disperses melanosomes. The expression of a gene for
      MCH was down-regulated by short wavelength light but up-regulated by mid-long
      wavelength light, whereas a gene for POMC was up-regulated under short wavelength
      light. Melanosomes in larvae (4 dpf) exposed to a black background aggregated
      when immersing the larvae in MCH solution. Yohimbine, an alpha2-adrenergic
      receptor antagonist, attenuated adrenaline-dependent aggregation in larvae
      exposed to a black background but did not induce melanosome dispersion in larvae
      exposed to a white background. These results suggest that MCH plays a key role in
      the light wavelength-dependent response of melanophores, flexibly mediating the
      transmission of light wavelength information between photoreceptors and
      melanophores.

PMID- 30195024
TI  - Angiopoietin expression in ovine corpora lutea during the luteal phase: Effects
      of nutrition, arginine and follicle stimulating hormone.
AB  - The aim of this study was to evaluate angiopoietin (ANGPT) 1 and 2, and tyrosine
      protein kinase receptor 2 (TIE2) expression in the corpora lutea (CL) of FSH
      treated, or non-treated sheep administered arginine (Arg) or vehicle (saline,
      Sal), and fed a control (C), excess (O) or restricted (U) diet. Ewes from each
      dietary group were treated with Arg or Sal (experiment 1), and with FSH
      (experiment 2). Luteal tissues were collected at the early-, mid- and/or late
      luteal phases of the estrous cycle. Protein and mRNA expression was determined
      using immunohistochemistry followed by image analysis, and quantitative RT-PCR,
      respectively. The results demonstrated that ANGPT1 and TIE2 proteins were
      localized to luteal capillaries and endothelial cells of larger blood vessels,
      and ANGPT2 was localized to tunica media of larger blood vessels. TIE2 protein
      was also present in luteal cells. In experiment 1, ANGPT1 protein expression was
      greater in O than C during early- and mid-luteal phases, and was greatest during
      late-luteal phase, less at the mid- and least at the early-luteal phase; 2) TIE2
      protein expression was greatest at the mid-, less at the early- and least at the
      late-luteal phase; 3) ANGPT1 and 2 mRNA expression was greater at the mid- and
      late- than the early-luteal phase, and TIE2 mRNA expression was greatest at the
      late-, less at the mid- and least at the early-luteal phase. The ANGPT1/2 ratio
      was less at the early- than mid- or late-luteal phases. In experiment 2, ANGPT1
      protein expression was greater in O during the mid-luteal phase than in other
      groups, and was greater at the mid- than early-luteal phase. TIE2 protein
      expression was highest at the mid-, less at the early- and least during the late
      luteal phase. ANGPT1 and 2, and TIE2 mRNA expression was higher at the mid- than
      the early-luteal phase. During mid-luteal phase, ANGPT1 mRNA expression was
      greater in C than O and U, ANGPT2 was greatest in C, less in O and least in U,
      and TIE2 mRNA expression was greater in C than O and U. The ANGPT1/2 ratio was
      higher in U than in any other group. Comparison of FSH vs. Sal treatment effects
      (experiment 2 vs. experiment 1) demonstrated that FSH affected ANGPT1 and/or -2,
      and TIE2 protein and mRNA expression depending on luteal phase and/or diet. Thus,
      expression of ANGPTs and TIE2 in the CL changes during the luteal lifespan,
      indicating their involvement in luteal vascular formation, stabilization and
      degradation. Moreover, this study has demonstrated that plane of nutrition and/or
      FSH treatment affect the ANGPT system, and may alter luteal vascularity and
      luteal function in sheep.

PMID- 30195025
TI  - Testis structure, spermatogonial niche and Sertoli cell efficiency in Neotropical
      fish.
AB  - Neotropical icthyofauna represents one of the most diverse and extreme ecosystems
      in the world. Likewise, reproduction showed enormous diversity with different
      reproductive systems, modes and behavior. On the other hand, information on
      Neotropical fish species, in particular on male reproductive physiology is
      restricted to few species. This mini-review aimed to compile the existing
      information on spermatogenesis of Neotropical teleosts focusing on testis
      structure, spermatogonial niche and Sertoli cell efficiency. The first topic
      covers the histological analysis of the testicular structure, showing a conserved
      testicular pattern in relation to the phylogenetic position: basal species
      present anastomosing tubular testis (e.g. Astyanax altiparanae, Conorhynchos
      conirostris, Pimelodus maculatus, Lophiosilurus alexandri, Rhinelepis aspera,
      among others), while derived teleosts showed lobular testis (e.g. Cichlasoma
      dimerus, Cichla kelberi, Odontesthes bonariensis, Synbranchus marmoratus and
      others). Next to testicular structure, existing data showed that type A
      undifferentiated spermatogonia (Aund) is differentially distributed among the
      Neotropical species. Aund can be restricted at the blind-end of the germinal
      compartment (O. bonariensis), or spread along the germinal epithelium (A.
      altiparanae), or even distributed along the germinal epithelium but concentrated
      at the blind-end (C. kelberi and C. intermedia). Moreover, recent studies in A.
      altiparanae have demonstrated that within the germinal compartment, Aund have a
      preferential distribution in areas neighboring the interstitial compartment - the
      spermatogonial niche. The proximity with the interstitium suggests that
      interstitial cells, such as Leydig cells, are important for Aund maintenance in
      the testis. Finally, this mini-review highlighted Sertoli cell efficiency,
      showing that a single Sertoli cell can support a higher number of germ cells (80
      140 spermatids) in Neotropical species evaluated at the moment (e.g. A.
      altiparanae, Hoplias malabaricus, Poecilia reticulata, Serrasalmus spilopleura,
      C. intermedia). Overall, this review provided basic and functional information on
      spermatogenesis of Neotropical species. More studies in this field are necessary
      since Neotropical region is considered one of the hotspot regions to discovery
      new species providing, therefore, new opportunities to investigate
      spermatogenesis in fish.

PMID- 30195026
TI  - Immunomodulation by testosterone and corticosterone in toads: Experimental
      evidences from transdermal application.
AB  - Androgens and glucocorticoids play important roles in vertebrate's reproduction
      and display complex immunomodulatory functions that may affect survival. In
      anurans, testosterone and corticosterone are correlated to sexual behavior,
      reproduction, and immune function. Male toads (Rhinella jimi) were treated with
      acute doses of testosterone (T) and corticosterone (CORT) and immune variables
      (plasma bacterial killing ability [BKA], swelling after phytohemagglutinin [PHA]
      injection and the time point of maximum PHA swelling response) were measured.
      Transdermal T and CORT application increased androgen (T-DHT) and CORT plasma
      levels after 1 h of treatment, respectively, without a dose-specific effect.
      Transdermal T treatment did not affect BKA or PHA swelling response. Individuals
      treated with transdermal CORT showed an earlier maximum PHA swelling response and
      a tendency of lower BKA 15 h after treatment. Our results indicated that an acute
      experimental increase of CORT plasma levels diminished time for inflammatory
      resolution and suppressed non-cellular innate response.

PMID- 30195027
TI  - Evidence that NLRC4 inflammasome mediates apoptotic and pyroptotic microglial
      death following ischemic stroke.
AB  - Stroke is the second leading cause of death in the world and a major cause of
      long-term disability. Recent evidence has provided insight into a newly described
      inflammatory mechanism that contributes to neuronal and glial cell death, and
      impaired neurological outcome following ischemic stroke - a form of sterile
      inflammation involving innate immune complexes termed inflammasomes. It has been
      established that inflammasome activation following ischemic stroke contributes to
      neuronal cell death, but little is known about inflammasome function and cell
      death in activated microglial cells following cerebral ischemia. Microglia are
      considered the resident immune cells that function as the primary immune defense
      in the brain. This study has comprehensively investigated the expression and
      activation of NLRP1, NLRP3, NLRC4 and AIM2 inflammasomes in isolates of
      microglial cells subjected to simulated ischemic conditions and in the brain
      following ischemic stroke. Immunoblot analysis from culture media indicated
      microglial cells release inflammasome components and inflammasome activation
      dependent pro-inflammatory cytokines following ischemic conditions. In addition,
      a functional role for NLRC4 inflammasomes was determined using siRNA knockdown of
      NLRC4 and pharmacological inhibitors of caspase-1 and -8 to target apoptotic and
      pyroptotic cell death in BV2 microglial cells under ischemic conditions. In
      summary, the present study provides evidence that the NLRC4 inflammasome complex
      mediates the inflammatory response, as well as apoptotic and pyroptotic cell
      death in microglial cells under in vitro and in vivo ischemic conditions.

PMID- 30195028
TI  - The beta2-adrenergic receptor controls inflammation by driving rapid IL-10
      secretion.
AB  - The mammalian nervous system communicates important information about the
      environment to the immune system, but the underlying mechanisms are largely
      unknown. Secondary lymphoid organs are highly innervated by sympathetic neurons
      that secrete norepinephrine (NE) as the primary neurotransmitter. Immune cells
      express adrenergic receptors, enabling the sympathetic nervous system to directly
      control immune function. NE is a potent immunosuppressive factor and markedly
      inhibits TNF-alpha secretion from innate cells in response to lipopolysaccharide
      (LPS). In this study, we demonstrate that NE blocks the secretion of a variety of
      proinflammatory cytokines by rapidly inducing IL-10 secretion from innate cells
      in response to multiple Toll-like receptor (TLR) signals. NE mediated these
      effects exclusively through the beta2-adrenergic receptor (ADRB2). Consequently,
      Adrb2-/- animals were more susceptible to L. monocytogenes infection and to
      intestinal inflammation in a dextran sodium sulfate (DSS) model of colitis.
      Further, Adrb2-/- animals rapidly succumbed to endotoxemia in response to a sub
      lethal LPS challenge and exhibited elevated serum levels of TNF-alpha and reduced
      IL-10. LPS-mediated lethality in WT animals was rescued by administering a beta 2
      specific agonist and in Adrb2-/- animals by exogenous IL-10. These findings
      reveal a critical role for ADRB2 signaling in controlling inflammation through
      the rapid induction of IL-10. Our findings provide a fundamental insight into how
      the sympathetic nervous system controls a critical facet of immune function
      through ADRB2 signaling.

PMID- 30195029
TI  - Energization and spoken language production: Evidence from progressive
      supranuclear palsy.
AB  - Energization is the process of initiating and sustaining a response over time. It
      has been described as one of three key "supervisory" attentional control
      processes associated with the frontal lobes. Attentional mechanisms, such as
      energization, are critical for a range of cognitive functions, such as
      spontaneous speech and other higher-order tasks. We aimed to investigate the
      process of energization in a case series of patients with progressive
      supranuclear palsy (PSP). Patients with a diagnosis of PSP (N = 5), patient
      controls with a neurodegenerative condition (Alzheimer's disease N = 3,
      frontotemporal dementia N = 2) and healthy older adult controls (N = 30) were
      assessed on a standard neuropsychological battery, including executive tasks and
      standard attention and language tests. Energization was investigated using word
      fluency tasks, samples of spontaneous speech and an experimental button-pressing
      concentration task. Response rates for the word fluency, spontaneous speech and
      concentration tasks were separated into time periods, in order to compare
      response rates at different points across the tasks (e.g., first 15 s vs. last 45
      s in a 60 s task). Four PSP patients showed a clear response pattern indicative
      of a decrease in energization. Healthy and patient controls remained consistent
      in their responding over time. Understanding how these underlying processes are
      impaired in PSP can ultimately inform intervention and management strategies, and
      has theoretical implications for models of spoken language production.

PMID- 30195030
TI  - Nucleoporin35 is a novel microtubule associated protein functioning in oocyte
      meiotic spindle architecture.
AB  - Nucleoporins (Nups) are a large and diverse family of proteins that mediate
      nucleocytoplasmic transport at interphase of vertebrate cells. Nups also function
      in mitosis progression. However, whether Nups are involved in oocyte meiosis
      progression is still rarely known. In this study, we delineated the roles and
      regulatory mechanisms of Nucleoporin35 (Nup35) during oocyte meiotic maturation.
      The immunofluorescent signal of Nup35 was localized in the nuclear membrane at
      germinal vesicle (GV) stage, the microtubules and spindle at pro-metaphase I (pro
      MI), metaphase I (MI), and metaphase II (MII), but to the spindle poles at
      anaphase I (AI) and telophase I (TI). The dynamic localization pattern of Nup35
      during oocyte meiotic maturation implied its specific roles. We also found that
      Nup35 existed as a putatively phosphorylated form after resumption of meiosis
      (GVBD), but not at GV stage, implying its functional switch from nuclear membrane
      to meiotic progression. Further study uncovered that knockdown of Nup35 by
      specific siRNA significantly compromised the extrusion of first polar body (PBE),
      but not GVBD, with defects of spindle assembly and chromosome alignment and
      dissociated some localization signal of p-ERK1/2 from spindle poles to cytoplasm.
      A defective kinetochore - microtubule attachment (K-MT) was also identified in
      oocytes after knockdown of Nup35, which activates spindle assembly checkpoint. In
      conclusion, our results suggest that Nup35 is putatively phosphorylated and
      released to the cytoplasm after resumption of meiosis, and regulates spindle
      assembly and chromosome alignment.

PMID- 30195031
TI  - ONO-5046 suppresses reactive oxidative species-associated formation of neutrophil
      extracellular traps.
AB  - BACKGROUND: Neutrophil extracellular traps (NETs) have been identified as a non
      apoptosis cell death pattern that leads to the release of granular contents into
      the extracellular space and subsequent excessive inflammatory response. The
      present study aims to investigate whether ONO-5046, a novel neutrophil elastase
      inhibitor, could affect NETs formation and promote inflammation resolution.
      METHODS: Neutrophils were separated and identified. Cell survival rate was
      analyzed using the trypan blue stain-resistance method. Different concentrations
      of lipopolysaccharide (LPS) (0.01 MUg/mL, 0.1 MUg/mL, and 1.0 MUg/mL) were used
      to stimulate NETs formation. ONO-5046 (0.1 MUg/mL and 1 MUg/mL) was administered
      after high-dose LPS stimulation and NETs formation. Moreover, tBHP was used to
      further investigate the relationships between the effects of ONO-5046 and
      reactive oxygen species (ROS) release. ROS was detected by DCFH-DA fluorescent
      staining and NETs formation was demonstrated via immunofluorescence staining for
      neutrophil elastase and citrullinated histone H3 (H3Cit). RESULTS: NETs formation
      was stimulated by LPS in a dose-dependent manner. High doses of LPS induced ROS
      generation and decreased cellular survival. ONO-5046 reduced LPS-induced NETs
      formation in a dose-dependent manner, as evidenced by immunofluorescence staining
      for neutrophil elastase and H3Cit whereby the fluorescence intensity decreased
      and neutrophil ROS generation was attenuated. However, the effects of ONO-5046 on
      NETs reduction were reversed by ROS inducer tBHP. CONCLUSIONS: The neutrophil
      elastase inhibitor ONO-5046 suppresses ROS-associated NETs formation, which may
      lead to inflammation resolution.

PMID- 30195033
TI  - Long non-coding RNAs in coronary atherosclerosis.
AB  - Coronary atherosclerosis (CAS), a leading cause of cardiovascular disease, is a
      major cause of death worldwide. CAS is a chronic disease in the aorta that can be
      caused by dyslipidemia, abnormal glucose metabolism, endothelial cell
      dysfunction, vascular smooth muscle cell (VSMC) or fibrous connective tissue
      hyperplasia, immune inflammatory reactions, and many other factors. The
      pathogenesis of CAS is not fully understood, as it is a complex lesion
      complicated by multiple factors. Damage-response theories have put forward
      endothelial cell (EC) injury as the initiating factor for CAS; the addition of
      lipid metabolism disorders may enhance monocyte adhesion, increase the
      proliferation and migration of fibroblasts and VSMCs, and accelerate the
      development of CAS. Furthermore, inflammatory and immune responses can create a
      vicious cycle of endothelial injury, which also plays key roles in the formation
      of CAS. Therefore, in order to elucidate the mechanisms controlling CAS, it is
      important to study the etiology of vascular cell dysfunction, abnormal energy and
      metabolism disorders, and immune and inflammatory reactions. Non-coding RNAs play
      regulatory roles in the pathogenesis of CAS, especially long non-coding RNAs
      (lncRNAs); lncRNAs have recently become a major focus for cardiovascular disease
      mechanisms, as they play numerous roles in the progression of CAS. Therefore, in
      this review, we discuss the role of lncRNAs in the pathogenesis of coronary CAS,
      and their role in the prevention and treatment of coronary CAS.

PMID- 30195032
TI  - Extracellular ubiquitin modulates cardiac fibroblast phenotype and function via
      its interaction with CXCR4.
AB  - AIMS: beta-adrenergic receptor (beta-AR) stimulation increases extracellular
      levels of ubiquitin (UB), and exogenous UB plays an important role in beta-AR
      stimulated myocardial remodeling with effects on heart function, fibrosis and
      myocyte apoptosis. Cardiac fibroblasts are vital for maintaining the normal
      function of the heart, and in the structural remodeling of the heart in response
      to injury. Here we hypothesized that extracellular UB modulates cardiac
      fibroblast phenotype and function via its interaction with CXC chemokine receptor
      type 4 (CXCR4). MAIN METHODS: Serum starved adult cardiac fibroblasts were used
      to identify CXCR4 as a receptor for UB. Fluorescent microscopy, co
      immunoprecipitation, western blot, proliferation, migration and collagen
      contraction assays were performed to investigate the role of UB/CXCR4 axis on
      cell signaling, and modulation of fibroblast phenotype and function. KEY
      FINDINGS: Using fluorescent microscopy and co-immunoprecipitation assay, we
      provide evidence that extracellular UB interacts with CXCR4. CXCR4 antagonist,
      AMD3100, inhibited interaction of UB with CXCR4. UB activated ERK1/2, not Akt. It
      enhanced VEGF-A expression, while decreasing beta3 integrins expression. Two
      mutated UB proteins (V70A and F4A; unable to interact with CXCR4) failed to
      affect the expression of VEGF-A and beta3 integrins. UB treatment inhibited
      migration of cells into the wound and FBS-stimulated cell proliferation. UB
      enhanced expression of alpha-smooth muscle actin (marker of myofibroblast
      differentiation) and contraction of fibroblast-populated collagen gel pads. Most
      of the effects of UB were negated by AMD3100. SIGNIFICANCE: The data presented
      here suggest that UB interacts with CXCR4, and UB/CXCR4 interaction affects
      intracellular signaling, and modulates fibroblast phenotype and function.

PMID- 30195034
TI  - The protective effects of acupoint gel embedding on rats with myocardial ischemia
      reperfusion injury.
AB  - AIMS: Prevention and treatment of myocardial ischemia-reperfusion (I/R) injury
      has for many years been a hot topic in treating ischemic heart disease. As one of
      the most well-known methods of complementary and alternative medicine,
      acupuncture has attracted increasing interest in preventing myocardial I/R injury
      due to its remarkable effectiveness and minimal side effect. However, traditional
      acupuncture approaches are limited by cumbersome execution, high labor costs and
      inevitable pain caused by frequent stimulation. Therefore, in this work, we aimed
      to develop a novel acupoint gel embedding approach and investigated its role in
      protecting against myocardial I/R injury in rats. MAIN METHODS: Gels were
      embedded at bilateral Neiguan (PC6) points of rats and their protective effects
      against myocardial I/R injury evaluated in terms of changes in histomorphology,
      myocardial enzymology, antioxidant capacity, anti-inflammatory response, and anti
      apoptosis of cells. KEY FINDINGS: We found that the approach of acupoint gel
      embedding could significantly reduce myocardial infarcted size, repair
      pathological changes, mitigate oxidative stress damage and inflammatory response,
      as well as inhibit apoptosis of cardiomyocytes. Such cardioprotective effects
      were found to be associated with Notch-1/Jagged-1 signaling pathway.
      SIGNIFICANCE: The proposed approach of acupoint gel embedding has advantages in
      continuous acupoint stimulation, dosing controls, and no side effects in the
      course of treatment, as well as in reducing the pain caused by frequent
      acupuncture. It can form an alternative therapy to not only protect against
      myocardial I/R injury but also hold great potential in treating other diseases in
      the future.

PMID- 30195035
TI  - Sitagliptin attenuates intestinal ischemia/reperfusion injury via cAMP/PKA,
      PI3K/Akt pathway in a glucagon-like peptide 1 receptor-dependent manner.
AB  - AIMS: This study investigated the effect of sitagliptin prophylactic treatment on
      intestinal I/R rat model and explored the possible underlying mechanism. MAIN
      METHODS: Forty-five male Sprague-Dawley rats were randomly assigned to 3 groups:
      Sham group (operation without clamping), I/R group (operation with clamping) and
      sitagliptin pretreated group (300 mg/kg/day; p.o.) for 2 weeks before I/R insult.
      Intestinal I/R was performed by clamping the superior mesenteric artery for 30
      min, followed by 60 min reperfusion after removal of clamping. At the end of the
      experimental period, all rats were sacrificed for histopathological, biochemical,
      PCR and western blot assessment. KEY FINDINGS: Pretreatment with sitagliptin
      remarkably alleviated the pathological changes induced by I/R in the jejunum,
      suppressed upregulated NF-kappaB, TNF-alpha, IL-1betaand MPO caused by I/R.
      Moreover, sitagliptin decreased the Bax/Bcl-2 ratio and accordingly suppressed
      apoptotic tissue damage as reflected by a caspase-3 level reduction in rat
      intestine subjected to I/R injury. Interestingly, sitagliptin could obviously
      increase the active GLP-1 level and GLP-1 receptor mRNA expression in the jejunum
      of I/R rats. This was associated with the augmentation of the cAMP level and
      enhancement of PKA activity. Simultaneously, sitagliptin treatment was able to
      increase the protein expression levels of phosphorylated PI3K and Akt.
      SIGNIFICANCE: Sitagliptin has shown protective effects against intestinal I/R
      injury in rats through reduction of intestinal inflammation and apoptosis. The
      molecular mechanisms may be partially correlated with activation of cAMP/PKA and
      PI3K/Akt signaling pathway by the GLP-1/GLP-1 receptor.

PMID- 30195036
TI  - Beneficial effects of phycobiliproteins from Spirulina maxima in a preeclampsia
      model.
AB  - AIMS: Considering phycobiliproteins of Spirulina maxima has shown a wide margin
      of security in pregnant and non-pregnant animals as well as antioxidant
      properties, present study aimed to investigate if the cardiovascular and
      metabolic effects of an experimental model of preeclampsia can be prevented by
      the administration of this compound. MAIN METHODS: Subrenal aortic coarctation
      (SRAC) practiced to female Wistar rats of 8 weeks of age. Animals were divided
      randomly to conform non-pregnant and pregnant groups and pregnant with SRAC
      showed fetoplacental ischemia and were considered preeclamptic (PE). Groups were
      treated with saline solution (control group) or phycobiliproteins solution (100
      mg/kg/day ig) for the last 7, 14 or 20 days of pregnancy. KEY FINDINGS: PE
      animals showed increased systolic blood pressure, weight gain, glucose and GTT as
      well as vascular contractility. Also, PE animals showed decreased SOD, GPx
      activities while MDA was increased. Phycobiliproteins oral treatment for 3 weeks
      significantly decreased systolic blood pressure and reestablished glucose, weight
      gain and vascular contractility as well as enzyme activities of PE rats to those
      of normal pregnant animals. SIGNIFICANCE: Our results show that phycobiliproteins
      can prevent the damage produced by fetoplacental ischemia and provides evidence
      of free radical species contribution to the physiopathology of the disease. Also,
      we conclude phycobiliproteins can be an alternative to reduce preeclampsia
      manifestations, however, more studies are recommended.

PMID- 30195038
TI  - Syndecan transmembrane domain modulates intracellular signaling by regulating the
      oligomeric status of the cytoplasmic domain.
AB  - Cell surface receptors must specifically recognize an extracellular ligand and
      then trigger an appropriate response within the cell. Their general structure
      enables this, as it comprises an extracellular domain that can bind an
      extracellular ligand, a cytoplasmic domain that can transduce a signal inside the
      cell to produce an appropriate response, and a transmembrane domain that links
      the two and is responsible for accurately delivering specific information on a
      binding event from the extracellular domain to the cytoplasmic domain, to trigger
      the proper response. A vast body of research has focused on elucidating the
      specific mechanisms responsible for regulating extracellular binding events and
      the subsequent interactions of the cytoplasmic domain with intracellular
      signaling. In contrast, far less work has focused on examining how the
      transmembrane domain links these domains and delivers the necessary information.
      In this review, we propose the importance of the transmembrane domain as a signal
      regulator. We highlight the cell adhesion receptor, syndecan, as a special case,
      and propose that the transmembrane domain-mediated oligomerization of the
      syndecan cytoplasmic domain is a unique regulatory mechanism in syndecan
      signaling.

PMID- 30195037
TI  - Growth arrest and DNA-damage-inducible 45 beta (GADD45beta) deletion suppresses
      testosterone-induced prostate hyperplasia in mice.
AB  - AIM: Growth arrest and DNA-damage-inducible 45 beta (GADD45beta) is a member of
      the gene family associated with cell growth control, apoptosis, and DNA damage
      repair. The aim of present study was to determine the potential effects of
      GADD45beta deletion on prostate hyperplasia progression. MAIN METHODS: LNCaP
      cells were incubated with testosterone propionate (1 MUM) for 48 h and specific
      siRNA used to suppress GADD45beta expression in vitro. For in vivo experiments,
      testosterone (3 mg/kg, IP) was injected into wild-type (WT) and GADD45beta
      knockout (GADD45beta-/-) C57BL/6J mice for 21 consecutive days, and serum and
      prostate tissues subjected to biological and histochemical analyses. KEY
      FINDINGS: GADD45beta-silenced LNCaP cells showed suppressed testosterone-induced
      5alpha-reductase 2 and androgen receptor expression compared to control LNCaP
      cells. Moreover, after 21 days of testosterone treatment, prostate weight and
      stromal tissue increment were relatively lower in GADD45beta-/- than WT
      counterpart mice. Inhibition of testosterone-induced 5alpha-reductase 2 and
      proliferating cell nuclear antigen expression in the GADD45beta-/- group was
      confirmed via immunohistochemistry analyses. SIGNIFICANCE: Although the exact
      correlation between GADD45beta and prostate hyperplasia remains to be
      established, the present GADD45betadeletion suppressed testosterone-induced
      prostate hyperplasia which was accompanied by inhibition of 5alpha-reductase 2
      related protein expression.

PMID- 30195039
TI  - Phylogenetic analysis of Antarctic notothenioids illuminates the utility of
      RADseq for resolving Cenozoic adaptive radiations.
AB  - Notothenioids are a clade of ~120 species of marine fishes distributed in extreme
      southern hemisphere temperate near-shore habitats and in the Southern Ocean
      surrounding Antarctica. Over the past 25 years, molecular and morphological
      approaches have redefined hypotheses of relationships among notothenioid lineages
      as well as their relationships among major lineages of percomorph teleosts. These
      phylogenies provide a basis for investigation of mechanisms of evolutionary
      diversification within the clade and have enhanced our understanding of the
      notothenioid adaptive radiation. Despite extensive efforts, there remain several
      questions concerning the phylogeny of notothenioids. In this study, we deploy DNA
      sequences of ~100,000 loci obtained using RADseq to investigate the phylogenetic
      relationships of notothenioids and to assess the utility of RADseq loci for
      lineages that exhibit divergence times ranging from the Paleogene to the
      Quaternary. The notothenioid phylogenies inferred from the RADseq loci provide
      unparalleled resolution and node support for several long-standing problems
      including, (1) relationships among species of Trematomus, (2) resolution of
      Indonotothenia cyanobrancha as the sister lineage of Trematomus, (3) the deep
      paraphyly of Nototheniidae, (4) the paraphyly of Lepidonotothen s.l., (5)
      paraphyly of Artedidraco, and 6) the monophyly of the Bathydraconidae. Assessment
      of site rates demonstrates that RADseq loci are similar to mtDNA protein coding
      genes and exhibit peak phylogenetic informativeness at the time interval during
      which the major Antarctic notothenioid lineages originated and diversified. In
      addition to providing a well-resolved phylogenetic hypothesis for notothenioids,
      our analyses quantify the predicted utility of RADseq loci for Cenozoic
      phylogenetic inferences.

PMID- 30195040
TI  - Using phylogenomics to reconstruct phylogenetic relationships within tribe
      Polygonateae (Asparagaceae), with a special focus on Polygonatum.
AB  - Polygonatum is a widespread temperate genus with approximately 75 species
      centered in the Eastern Himalaya and Indo-Burma biodiversity hotspots. A complete
      assessment of the remarkable diversity of Polygonatum in these areas requires an
      accurate circumscription of the genus, as well as a clear understanding of
      generic and infrageneric relationships, both of which have been problematic in
      the past. In this study, we reconstruct phylogenetic relationships within
      Polygonatum and test its monophyly using a phylogenomic approach. For that, we
      built a comprehensive dataset that includes complete or nearly-complete plastid
      genomes of 19 species of Polygonatum, one of Disporopsis, and four of
      Heteropolygonatum. Their plastid genomes do not present any major structural
      differences and range from 153,821 to 155,580 bp in length. Molecular
      phylogenetic analyses of the chloroplast coding regions indicate that Polygonatum
      and Heteropolygonatum are monophyletic, providing support for their recognition
      as distinct genera and corroborating recent adjustments of their
      circumscriptions. An expanded analysis with higher species sampling using the
      petA-psbJ plastid gene region combined with the nuclear ribosomal ITS provided
      support for the recognition of three distinct sections within Polygonatum. These
      same sections are further supported by chromosome data: Polygonatum sect.
      Sibirica (x = 12); Polygonatum sect. Polygonatum (x = 9-11); and, Polygonatum
      sect. Verticillata (x = 13-15). Populations of P. multiflorum from northwestern
      Himalaya are here shown to be best treated as a separate taxon, P. govanianum.
      Furthermore, P. verticillatum is shown to be polyphyletic, indicating that it
      represents a species-complex that includes multiple Asiatic species. Despite
      that, additional studies are still needed until the proper nomenclatural
      adjustments can be made.

PMID- 30195041
TI  - Alpha-mangostin, an active compound in Garcinia mangostana, abrogates anoikis
      resistance in human hepatocellular carcinoma cells.
AB  - Anoikis-resistance is a critical step in cancer progression, especially during
      the process of metastasis. During this phase, the cancer phenotype that causes
      cell survival in detachment conditions, drug resistance, and epithelial-to
      mesenchymal transition (EMT) is altered. Inhibition of anoikis-resistance can
      potentially be the molecular target in cancer therapy. Alpha-mangostin, an active
      compound in Garcinia mangostana, has been reported for its cell-death induction
      and its chemosensitizing and anti-metastatic properties in many cancer cell
      types, such as ovarian cancer, lung cancer, and hepatocellular carcinoma. We,
      therefore, have investigated whether alpha-mangostin could sensitize anoikis in
      human hepatocellular carcinoma (HepG2). The established anoikis-resistant HepG2
      displayed more aggressive malignant behaviors, including rapid proliferation,
      doxorubicin resistance, up-regulated anti-apoptotic protein levels, and EMT
      phenotype. Alpha-mangostin significantly sensitized anoikis in HepG2 through the
      inhibition of cell survival by induced caspase-9, caspase-8 and caspase-3
      activities, increased pro-apoptotic protein (Bax, Bim, t-Bid) levels, and
      decreased anti-apoptotic protein (c-FLIP, Mcl-1) levels. Besides, alpha-mangostin
      significantly reduced cell re-adhesion and migration, matrix metalloproteinases-2
      (MMP-2) and MMP-9 secretions, and EMT-involved protein (N-cadherin, alphaV, beta1
      integrin, and vimentin) expressions. AKT and ERK signaling pathways were
      dramatically suppressed, which indicated that alpha-mangostin inhibited anoikis
      resistance via the inhibition of these pathways in HepG2. These findings support
      the development of alpha-mangostin to be used in the treatment of anoikis
      resistant liver cancer.

PMID- 30195043
TI  - The Impact of Alcohol Use Disorders on Pulmonary Immune Cell Inflammatory
      Responses to Streptococcus pneumoniae.
AB  - Community-acquired pneumonia due to Streptococcus pneumoniae occurs commonly in
      alcohol use disorders (AUDs). Pneumonia in the AUD patient is associated with
      poorer outcomes, and specific therapies to mitigate disease severity in these
      patients do not exist. Numerous investigations have attributed increased severity
      of pneumonia in AUDs to aberrant function of the alveolar macrophage (AM), a lung
      immune cell critical in host defense initiation. No studies have examined the
      response of human AMs to S. pneumoniae in AUDs. We hypothesized that the
      inflammatory mediators released by AMs after S. pneumoniae stimulation would
      differ quantitatively in individuals with AUDs compared to non-AUD participants.
      We further postulated that AM inflammatory mediators would be diminished after
      exposure to the antioxidant, N-acetylcysteine (NAC). For comparison, responses of
      peripheral blood mononuclear cells (PBMCs) to pneumococcal protein were also
      examined. Otherwise healthy participants with AUDs and smoking-matched controls
      underwent bronchoalveolar lavage and peripheral blood sampling to obtain AMs and
      PBMCs, respectively. Freshly collected cells were cultured with increasing doses
      of heat-killed S. pneumoniae protein, with and without exposure to N
      acetylcysteine. Cell culture supernatants were collected, and inflammatory
      mediators were measured, including interferon (IFN)-gamma, interleukin (IL)
      1beta, IL-6, and tumor necrosis factor (TNF)-alpha. IFN-gamma and IL-6 were
      significantly higher in unstimulated AM cell culture supernatants from subjects
      with AUDs. After stimulation with pneumococcal protein, a dose-response and time
      dependent increase in pro-inflammatory cytokine production by both AMs and PBMCs
      was also observed; differences were not observed between AUD and non-AUD
      subjects. Addition of NAC to pneumococcal-stimulated AMs and PBMCs was generally
      associated with diminished cytokine production, with the exception of IL-1beta
      that was elevated in AM culture supernatants from subjects with AUDs. Our
      observations suggest that AUDs contribute to basal alterations in AM pro
      inflammatory cytokine elaboration, but did not support consistent differences in
      pneumococcal-stimulated AM or PBMC inflammatory mediator secretion that were
      referable to AUDs.

PMID- 30195042
TI  - Antioxidant and pro-oxidant mechanisms of (+) catechin in microsomal CYP2E1
      dependent oxidative stress.
AB  - The objectives of this work were to evaluate the effects of catechin on
      cytochrome P450 2E1 (CYP2E1)-dependent oxidative stress. Microsomes co-expressing
      human CYP2E1 with NADPH cytochrome P450 reductase and cytochrome b5 were
      incubated with NADPH and DTPA at pH 7.0. Superoxide anion generation was
      specifically detected by spin-trapping with DEPMPO. Generation of the DEPMPO-OOH
      adduct was not observed in the absence of CYP2E1 and in the presence of
      superoxide dismutase (SOD) or catechin, while catalase was ineffective. Reactive
      oxygen species generation was detected with 1-hydroxy-3-carboxy-2,2,5,5
      tetramethylpyrrolidine (CPH) by the EPR-detection of its oxidation product, 3
      carboxy-proxyl radical (CP?). CP? generation was not observed in the absence of
      CYP2E1 and in the presence of SOD, while catalase was ineffective. In contrast,
      catechin increased CPH oxidation, an effect that was not observed in the absence
      of CYP2E1 or in the presence of SOD (but not catalase), and was not associated
      with an increase in oxygen consumption. Catechin also increased the non-specific
      oxidation of the probes CPH and hydroethidine by the superoxide anion-generating
      system xanthine plus xanthine oxidase. Catechin oxidized CPH in the presence of
      horseradish peroxidase plus hydrogen peroxide, a catechin radical-generating
      system. In conclusion, catechin exhibits both antioxidant (superoxide-scavenging)
      and pro-oxidant effects under CYP2E1-dependent oxidative stress.

PMID- 30195044
TI  - A novel method for assessing proximal tibiofibular joint on MR images in patients
      with knee osteoarthritis.
AB  - OBJECTIVES: To validate a method to measure the morphological parameters of the
      proximal tibiofibular joint (PTFJ) in patients with knee osteoarthritis (OA).
      METHODS: 408 participants were examined in this cross-sectional subject-based
      study. We calculated the fibular contacting area of PTFJ (S) and its projection
      areas onto the horizontal plane (load-bearing area, Stau), the sagittal plane
      (lateral stress-bolstering area, Sphi) and the coronal plane (posterior stress
      bolstering area, Supsilon). Joint space narrowing (JSN) and osteophyte was
      measured using radiographs. Cartilage defects, bone marrow lesions (BMLs) and
      cartilage volume were evaluated using magnetic resonance imaging (MRI). RESULTS:
      The average PTFJ fibular contacting area was 2.4 cm2 (SD, +/-0.7 cm2). Intra
      observer and inter-observer reliabilities of measures of PTFJ morphological
      parameters were excellent (>=0.90). S, Stau and Sphi were significantly
      associated with JSN in the medial tibiofemoral compartment (PR: 1.40, 95% CI 1.10
      1.78; PR: 1.65, 95% CI 1.25-2.18 and PR: 0.53, 95% CI 0.29-0.97, respectively).
      There was a significantly positive association between S, Stau and medial and/or
      femoral tibial cartilage defects. S, Stau and Supsilon were significantly and
      positively associated with medial and/or femoral tibial BMLs (PR: 1.36, 95% CI
      1.12-1.64; PR: 1.47, 95% CI 1.17-1.83; and PR: 1.39, 95% CI 1.06-1.82,
      respectively) after adjustment. S and Stau were significantly and negatively
      associated with medial tibial cartilage volume. CONCLUSIONS: This novel method to
      assess the morphological parameters of PTFJ in MRI is reproducible. These
      parameters are associated with knee radiographic and MRI-based OA-related
      structural abnormalities, suggesting clinical construct validity. Its predictive
      validity needs to be examined in future longitudinal studies.

PMID- 30195045
TI  - Functional assessment of strains around a full-thickness and critical sized
      articular cartilage defect under compressive loading using MRI.
AB  - OBJECTIVE: The objective of this study was to evaluate the effect of full
      thickness chondral defects on intratissue deformation patterns and matrix
      constituents in an experimental model mimicking in vivo cartilage-on-cartilage
      contact conditions. DESIGN: Pairs of bovine osteochondral explants, in a unique
      cartilage-on-cartilage model system, were compressed uniaxially by 350 N during 2
      s loading and 1.4 s unloading cycles (~1700 repetitions). Tissue deformations
      under quasi-steady state load deformation response were measured with
      displacement encoded imaging with stimulated echoes (DENSE) in a 9.4 T magnetic
      resonance imaging (MRI) scanner. Pre- and post-loading, T1, T2 and T1rho
      relaxation time maps were measured. We analyzed differences in strain patterns
      and relaxation times between intact cartilage (n = 8) and cartilage in which a
      full-thickness and critical sized defect was created (n = 8). RESULTS: Under
      compressive loading, strain magnitudes were elevated at the defect rim, with
      elevated tensile and compressive principal strains (Deltaepsilonmax = 4.2%, P =
      0.02; Deltaepsilonmin = -4.3%, P = 0.02) and maximum shear strain at the defect
      rim (Deltagammamax = 4.4%, P = 0.007). The opposing cartilage showed minimal
      increase in strain patterns at contact with the defect rim but decreased strains
      opposing the defect. After defect creation, T1, T2 and T1rho relaxation times
      were elevated at the defect rim only. Following loading, the overall relaxations
      times of the defect tissue and especially at the rim, increased compared to
      intact cartilage. CONCLUSIONS: This study demonstrates that the local
      biomechanical changes occurring after defect creation may induce tissue damage by
      increasing shear strains and depletion of cartilage constituents at the defect
      rim under compressive loading.

PMID- 30195046
TI  - The role of NOX2-derived reactive oxygen species in collagenase-induced
      osteoarthritis.
AB  - OBJECTIVE: Synovitis in collagenase-induced osteoarthritis (CiOA) is driven by
      locally released S100A8/A9 proteins and enhances joint destruction. S100A8/A9 can
      induce reactive oxygen species (ROS) release by phagocytes in OA synovium via
      neutrophil cytosolic factor-1 (Ncf1)-regulated NOX2 activation. In the present
      study we investigated whether NOX2-derived ROS affect joint pathology during
      CiOA. METHODS: CiOA was induced in knee joints of wild type (WT) and Ncf1
      deficient (Ncf1**) mice. Synovial gene expression of NOX2-subunits was measured
      with quantitative real-time polymerase chain reaction (qRT-PCR). Joint pathology
      was assessed using histology and immunohistochemistry for aggrecan neo-epitope
      VDIPEN. Levels of inflammatory proteins were measured with Luminex or ELISA.
      Phagocytes in synovium, blood, bone marrow (BM) and spleen were analyzed with
      flow cytometry. ROS release by phagocytes was measured with a ROS detection kit.
      RESULTS: CiOA induction in knee joints of WT mice caused significantly increased
      synovial gene expression of NOX2 subunits. On day 7 of CiOA, cartilage damage and
      MMP activity, as measured by VDIPEN, were comparable between WT and Ncf1** mice.
      Synovial thickening, synovial S100A8/A9 levels and percentages of synovial
      macrophages, polymorphonuclear cells (PMNs), and monocytes were not different, as
      were levels of inflammatory mediators in serum and phagocyte percentages in
      blood, BM and spleen. On day 42 of CiOA, synovitis, cartilage damage, and
      osteophyte formation in Ncf1** mice were unaltered when compared to WT mice. ROS
      detection confirmed that Ncf1** PMNs lack functional NOX2, but in vitro
      macrophages showed ROS production, suggesting activation of compensatory
      mechanisms. CONCLUSIONS: Absence of Ncf1-mediated ROS production does not alter
      joint pathology in CiOA.

PMID- 30195047
TI  - The impact of chronic fluoxetine on conditioned fear expression and hippocampal
      FGF2 in rats: Short- and long-term effects.
AB  - Phenotypic differences in conditioned fear expression may be a marker of
      vulnerability to the development of anxiety disorders. Hippocampal FGF2
      correlates negatively with conditioned fear expression, and antidepressants, the
      first-line pharmacological treatment for anxiety, increase hippocampal FGF2. In
      the present study, we assessed whether treatment with the selective serotonin
      reuptake inhibitor fluoxetine reduces conditioned fear expression in rats that
      naturally express lower (Low fear) or higher (High fear) levels of fear following
      a single-trial conditioning session. Experiment 1 demonstrated that phenotypic
      differences in fear expression were highly stable over a two-week interval.
      Experiment 2 demonstrated that two weeks of fluoxetine treatment (administered
      via drinking water) reduced conditioned fear expression in both Low and High fear
      rats. Experiment 3 demonstrated that two weeks of fluoxetine reduced conditioned
      fear expression even when treatment commenced two weeks after fear conditioning,
      but not when conditioned fear was assessed following a two-week drug-free washout
      period. Additionally, fluoxetine increased hippocampal FGF2 levels relative to
      vehicle-treated rats, but only when measured immediately after fluoxetine
      treatment, and not two weeks after treatment termination. Together, these results
      provide further indirect evidence that endogenous hippocampal FGF2 may mediate
      individual differences in conditioned fear expression. They also suggest that
      fluoxetine may be effective in reducing conditioned fear expression in both
      vulnerable and resilient populations when administered immediately, or sometime
      after, aversive experiences, but these effects do not persist once treatment is
      terminated.

PMID- 30195048
TI  - Impact of 1-day and 4-day MWM training techniques on oxidative and neurochemical
      profile in rat brain: A comparative study on learning and memory functions.
AB  - Among multiple behavioral tasks used to assess memory performance, Morris water
      maze (MWM) is a well-known and reliable conventional behavioral task to monitor
      spatial memory performance in rodents. Although multiple procedures are employed
      by researchers for spatial learning training in MWM, but less is known about
      impact of these training protocol variations on oxidative and neurochemical
      systems. Therefore, this study aimed to examine whether variations in training
      protocol will influence spatial memory performance and induce changes in
      oxidative status and cholinergic and aminergic neurotransmission in rat brain.
      For this, rats were assigned to four groups; control (unexposed), 1-trial
      (exposed to single training trial), 1-day (exposed to four training trials for a
      single day) and 4-day (exposed to four training trials for four days). After
      conducting training, spatial reference memory performance was determined by
      performing retention and consolidation probe trials. Rats were then decapitated
      and their brain and plasma samples were collected for biochemical, oxidative and
      neurochemical analysis. It was found that spatial reference memory was improved
      following both 1-day and 4-day training protocols, however, corticosterone levels
      were raised extensively following 4-day training exposure compared to 1-day
      training protocol. Similarly, a significant improvement in redox profile and
      cholinergic and aminergic neurotransmitters was also observed following 1-day
      training procedure. Thus, 1-day training procedure can be suggested as a better
      procedure for assessing the spatial memory performance in rats as it has a
      profound impact on antioxidant status and cholinergic and aminergic
      neurotransmission in brain. Moreover, use of single-day training procedure can
      provide a rapid and effective tool for assessing spatial memory in rats compared
      to prolonged and complicated 4-day training protocol.

PMID- 30195049
TI  - Stress influences the dynamics of hippocampal structural remodeling associated
      with fear memory extinction.
AB  - Fear extinction is defined as a decline in fear-conditioned responses following
      non-reinforced exposure to a fear conditioned stimulus, therefore the conditioned
      stimulus gains new predictive properties. Patients with anxiety related disorders
      (e.g.: PTSD) subjected to extinction-like exposure treatments often experience a
      relapse of symptoms. Stress is a risk factor for those psychiatric disorders and
      a critical modulator of fear learning that turns the memory resistant to the
      extinction process. Dendritic spines are the anatomical sites where neuronal
      activity reshapes brain networks during learning and memory processes. Thus, we
      planned to characterize the dynamics of synaptic remodeling before and after
      contextual fear extinction in the dorsal hippocampus (DH), and how this process
      is affected by a previous stress experience. Animals with or without previous
      stress were contextually fear conditioned and one day later trained in an
      extinction paradigm. Rats were sacrificed one day after conditioning (pre
      extinction) or one day after extinction for spine density analysis in the DH. We
      confirmed that stress exposure induced a deficit in extinction learning. Further,
      a higher density of dendritic spines, particularly mature ones, was observed in
      the DH of non-stressed conditioned animals at pre-extinction. Interestingly,
      after extinction, the spine levels returned to the control values. Conversely,
      stressed animals did not show such spines boost (pre-extinction) or any other
      change (post-extinction). In contrast, such standard dynamics of dendritic
      changes as well as the behavioral extinction was recovered when stressed animals
      received an intra-basolateral amygdala infusion of midazolam prior to stress.
      Altogether, these findings suggest that stress hinders the normal dynamic of
      dendritic remodeling after fear extinction and this could be part of the
      neurobiological substrate that makes those memories resistant to be extinguished.

PMID- 30195050
TI  - Postnatal exposure to poly (I:C) impairs learning and memory through changes in
      synaptic plasticity gene expression in developing rat brain.
AB  - Viral infection during early stage of life influences brain development and
      results in several neurodevelopmental disorders such as schizophrenia, autism and
      behavioral abnormalities. However, the mechanism through which infection causes
      long-term behavioral defects is not well known. To elucidate this, we have used
      synthetic polyinosinic-polycytidylic acid [poly (I:C)] which acts as a dsRNA
      molecule and interacts with toll-like receptor-3 (TLR-3) of microglia cells to
      evoke the immune system, thus mimicking the viral infection. Rat pups of
      postnatal day (PND) 7 were infused with a single dose of poly (I:C) (5 mg/kg BW)
      and vehicle alone to controls. When these pups grew to 3, 6 and 12 weeks, their
      spatial and fear conditioning memory were impaired as assessed by Morris water
      maze and passive avoidance test, respectively. We checked the immune activation
      by staining of TNF-alpha in the hippocampus and observed that poly (I:C) exposure
      elevated the number of TNF-alpha positive cells immediately after 12 h of
      infusion in one week rat and it persisted up to postnatal age of 3 and 12 weeks.
      Moreover, poly (I:C) significantly decreased the binding of 3H-QNB to the
      cholinergic receptors in the frontal cortex and hippocampus of 3 and 6 weeks rats
      as compared to control but did not change significantly in 12 weeks rats. RT-PCR
      and immunoblotting results showed that poly (I:C) exposure upregulated the
      expression of memory associated genes (BDNF, Arc, EGR1) at mRNA and protein level
      in frontal cortex and hippocampus of 3 weeks rats as compared to control.
      However, long-time persistence of poly (I:C) effects significantly decreased the
      expression of these genes in both brain regions of 12 weeks rats. Taken together,
      it is evident that early life exposure to poly (I:C) has a long-term effect and
      impairs learning and memory, probably through TNF-alpha mediated
      neuroinflammation and alteration in the expression of memory associated genes in
      frontal cortex and hippocampus of rats.

PMID- 30195051
TI  - Structure basis of the improved sweetness and thermostability of a unique double
      sites single-chain sweet-tasting protein monellin (MNEI) mutant.
AB  - The sweet protein monellin has an intensely sweet potency but limited stability.
      We have identified a double-sites mutant (E2N/E23A) of the single-chain monellin
      (MNEI) with both improved sweetness (about 3-fold) and thermostability (10 
      degrees C). However, the structural basis of its superior properties remains
      elusive until now. Herein we report its crystal structure at a resolution 1.90 A.
      Similar to the wild-type, E2N/E23A adopts a wedge-shaped structure consisting of
      a five-strand beta-sheet partially "wrapped" around an alpha-helix. However,
      distinguishing parts were present in the loops region, including a remarkable
      conformation shift from beta-strand to loop around residue R39. Molecular docking
      revealed the persistence of conserved protein-receptor interface and formation of
      new intermolecular ionic bonds in the E2N/E23A-receptor complex involving the
      taste-active residue R39 of the sweet protein, which could account for its
      significant improvement of sweetness. On the other hand, a rearrangement of
      intramolecular interaction network including the C-H ... pi bond between A23 and
      F89 that led to enhanced hydrophobicity in the protein core, could be correlated
      with its improved thermostability. Furthermore, two new sweeter mutants of MNEI
      were created. These findings highlight the critical roles of key sweetness
      determinant residue R39 and hydrophobicity at the protein core for the sweetness
      and thermostability of the protein, respectively, which thus provide a deeper
      insight for understanding the structure-function relationship of the sweet
      protein as well as guidance for rational design of this unique biomacromolecule.

PMID- 30195052
TI  - Identification of a novel member of 2H phosphoesterases, 2',5'-oligoadenylate
      degrading ribonuclease from the oyster Crassostrea gigas.
AB  - Several genes of IFN-mediated pathways in vertebrates, among them the genes that
      participate in the 2',5'-oligoadenylate synthetase (OAS)/RNase L pathway, have
      been identified in C. gigas. In the present study, we identified genes, which
      encode proteins having 2',5'-oligoadenylate degrading activity in C. gigas. These
      proteins belong to the 2H phosphoesterase superfamily and have sequence
      similarity to the mammalian A kinase anchoring protein 7 (AKAP7) central domain,
      which is responsible for the 2',5'-phosphodiesterase (2',5'-PDE) activity.
      Comparison of the genomic structures of C. gigas proteins with that of AKAP7
      suggests that these enzymes originate from a direct common ancestor. However, the
      identified nucleases are not typical 2',5'-PDEs. The found enzymes catalyse the
      degradation of 2',5'-linked oligoadenylates in a metal-ion-independent way,
      yielding products with 2',3' -cyclic phosphate and 5'-OH termini similarly to the
      3'-5' bond cleavage in RNA, catalyzed by metal-independent ribonucleases. 3',5'
      linked oligoadenylates are not substrates for them. The preferred substrates for
      the C. gigas enzymes are 5'-triphosphorylated 2',5'-oligoadenylates, whose major
      cleavage reaction results in the removal of the 5'-triphosphorylated 2',3'-cyclic
      phosphate derivative, leaving behind the respective unphosphorylated 2',5'
      oligoadenylate. Such a cleavage reaction results in the direct inactivation of
      the biologically active 2-5A molecule. The 2',5'-ribonucleases (2',5'-RNases)
      from C. gigas could be members of the ancient group of ribonucleases, specific to
      2'-5' phosphodiester bond, together with the enzyme that was characterized
      previously from the marine sponge Tethya aurantium. The novel 2',5'-RNases may
      play a role in the control of cellular 2-5A levels, thereby limiting damage to
      host cells after viral infection.

PMID- 30195053
TI  - Alteration of functional brain architecture in 22q11.2 deletion syndrome -
      Insights into susceptibility for psychosis.
AB  - The 22q11.2 deletion is one of the most common copy number variants in humans.
      Carriers of the deletion have a markedly increased risk for neurodevelopmental
      brain disorders, including schizophrenia, autism spectrum disorders, and
      attention deficit hyperactivity disorder. The high risk of psychiatric disorders
      associated with 22q11.2 deletion syndrome offers a unique possibility to identify
      the functional abnormalities that precede the emergence of psychosis. Carriers of
      a 22q11.2 deletion show a broad range of sensory processing and cognitive
      abnormalities similar as in schizophrenia, such as auditory and visual sensory
      processing, response inhibition, working memory, social cognition, reward
      processing and arithmetic processing. All these processes have a significant
      negative impact on daily life if impaired and have been studied extensively in
      schizophrenia using task-based functional neuroimaging. Here, we review task
      related functional brain mapping studies that have used electroencephalography or
      functional magnetic resonance imaging to identify functional alterations in
      carriers with 22q11.2 deletion syndrome within the above mentioned cognitive and
      sensory domains. We discuss how the identification of functional changes at the
      brain system level can advance the general understanding of which neurobiological
      alterations set the frame for the emergence of neurodevelopmental disorders in
      the human brain. The task-based functional neuroimaging literature shows
      conflicting results in many domains. Nevertheless, consistent similarities
      between 22q11.2 deletion syndrome and schizophrenia have been found for sensory
      processing, social cognition and working memory. We discuss these functional
      brain alterations in terms of potential biomarkers of increased risk for
      psychosis in the general population.

PMID- 30195054
TI  - The landscape of NeuroImage-ing research.
AB  - As the field of neuroimaging grows, it can be difficult for scientists within the
      field to gain and maintain a detailed understanding of its ever-changing
      landscape. While collaboration and citation networks highlight important
      contributions within the field, the roles of and relations among specific areas
      of study can remain quite opaque. Here, we apply techniques from network science
      to map the landscape of neuroimaging research documented in the journal
      NeuroImage over the past decade. We create a network in which nodes represent
      research topics, and edges give the degree to which these topics tend to be
      covered in tandem. The network displays small-world architecture, with
      communities characterized by common imaging modalities and medical applications,
      and with hubs that integrate these distinct subfields. Using node-level analysis,
      we quantify the structural roles of individual topics within the neuroimaging
      landscape, and find high levels of clustering within the structural MRI subfield
      as well as increasing participation among topics related to psychiatry. The
      overall prevalence of a topic is unrelated to the prevalence of its neighbors,
      but the degree to which a topic becomes more or less popular over time is
      strongly related to changes in the prevalence of its neighbors. Finally, we
      incorporate data from PNAS to investigate whether it serves as a trend-setter for
      topics' use within NeuroImage. We find that popularity trends are correlated
      across the two journals, and that changes in popularity tend to occur earlier
      within PNAS among growing topics. Broadly, this work presents a cohesive model
      for understanding the emergent relationships and dynamics of research topics
      within NeuroImage.

PMID- 30195055
TI  - Reduced Nicotinamide Adenine Dinucleotide Phosphate Inhibits MPTP-Induced
      Neuroinflammation and Neurotoxicity.
AB  - It is generally believed that oxidative stress and neuroinflammation are
      implicated in the pathogenesis of Parkinson's disease (PD). Reduced nicotinamide
      adenine dinucleotide phosphate (NADPH) has been demonstrated to have potent
      neuroprotective effects against oxidative stress. In the present research, we
      investigated if NADPH could offer neuroprotection by inhibiting glia-mediated
      neuroinflammation induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP),
      a mechanism contributing to PD pathogenesis. The current data demonstrated that
      MPTP/MPP+ increased levels of reactive oxygen species (ROS), activated glial
      cells, and inflammasome proteins in the substantia nigra (SNpc), in addition to
      inducing the nuclear translocation of nuclear factor-kappaB (NF-kappaB) and
      phosphorylation of p38 MAPK. These responses were inhibited by supplementation of
      exogenous NADPH. Moreover, NADPH effectively decreased MPP+-induced excessive
      production of ROS, p38 phosphorylation and inflammatory protein of
      Cyclooxygenase2 (COX2) in cultured microglial BV-2 cells in vitro studies.
      Similarly, the p38 MAPK inhibitor SB203580 suppressed the upregulation of MPP+
      induced p38 phosphorylation and COX2 protein levels. Co-culture of neuronal cells
      with MPP+-primed BV-2 cells increased the levels of tumor necrosis factor-alpha
      (TNF-alpha) and induced cell death of neuronal cells. These effects were
      diminished by TNF-alpha neutralizing antibody and NADPH. NADPH reduced motor
      dysfunction and the loss of dopaminergic (DA) cells induced by MPTP. Therefore,
      the present study demonstrates that NADPH protects DA neurons by inhibiting
      oxidative stress and glia-mediated neuroinflammation both in vitro and in vivo,
      thus suggesting a potential of clinical application for PD and other
      neurodegenerative diseases.

PMID- 30195056
TI  - Locomotor Training Promotes Time-dependent Functional Recovery after Experimental
      Spinal Cord Contusion.
AB  - Locomotor training (LT) has been exhaustively investigated as a treatment for the
      spinal cord injury (SCI), however the literature reports both positive and
      negative effects over the functional recovery. The initiation period of LT
      following SCI is one of the major variables that needs attention. To investigate
      the better period, three different starting times were investigated after SCI in
      rats. Methods: Wistar rats were randomly divided into groups: control, SCI (rats
      with spinal cord contusion), and SCI groups exposed to LT starting 7, 14 or 28
      days after the injury (SCI-T7, SCI-T14 and SCI-T28). LT was performed on a
      treadmill, five days a week, 20 minutes per day, for ten weeks. Basso, Breattie
      and Bresnahan (BBB) scale and Horizontal Ladder walking test were used to
      evaluate the motor function; at the end, morphological and biochemical analyses
      of the spinal cords, tibialis anterior and soleus muscles were performed.
      Results: SCI-T14 and SCI-T28 groups had an improvement in both behavioral tests,
      while SCI-T7 presented a worsening in the functional performance. Late training
      groups preserved motoneurons in the spinal cord, showed larger muscle fiber areas
      and higher BDNF expression in tibialis anterior muscle. SCI-T7 group had higher
      lesion volume after LT in comparison with the SCI group. Late onset of LT
      promoted an increment of the hindlimb function, while early onset of training
      worsened the functional recovery of the SCI animals. These results demonstrate a
      critical LT starting time after the injury, contributing to define the best
      therapeutic window for rehabilitation.

PMID- 30195058
TI  - The new paradigm for androgenetic alopecia and plant-based folk remedies: 5alpha
      reductase inhibition, reversal of secondary microinflammation and improving
      insulin resistance.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Research in the past half a century has gradually
      sketched the biological mechanism leading to androgenetic alopecia (AGA). Until
      recently the aetiological paradigm has been too limited to enable intelligent
      commentary on the use of folk remedies to treat or reduce the expression of this
      condition. However, our understanding is now at a point where we can describe how
      some folk remedies work, predict how effective they will be or why they fail.
      RESULTS: The new paradigm of AGA is that inheritance and androgens
      (dihydrotestosterone) are the primary contributors and a secondary pathology,
      microinflammation, reinforces the process at more advanced stages of follicular
      miniaturisation. The main protagonist to microinflammation is believed to be
      microbial or Demodex over-colonisation of the infundibulum of the pilosebaceous
      unit, which can be ameliorated by antimicrobial/acaricidal or anti-inflammatory
      therapies that are used as adjuvants to androgen dependent treatments (either
      synthetic or natural). Furthermore, studies reveal that suboptimal androgen
      metabolism occurs in both AGA and insulin resistance (low SHBG or high DHT),
      suggesting comorbidity. Both can be ameliorated by dietary phytochemicals, such
      as specific classes of phenols (isoflavones, phenolic methoxy abietanes,
      hydroxylated anthraquinones) or polycyclic triterpenes (sterols, lupanes), by
      dual inhibition of key enzymes in AGA (5alpha-reductase) and insulin resistance
      (ie., DPP-4 or PTP1B) or agonism of nuclear receptors (PPARgamma). Evidence
      strongly indicates that some plant-based folk remedies can ameliorate both
      primary and secondary aetiological factors in AGA and improve insulin resistance,
      or act merely as successful adjuvants to mainstream androgen dependent therapies.
      CONCLUSION: Thus, if AGA is viewed as an outcome of primary and secondary
      factors, then it is better that a 'multimodal' or 'umbrella' approach, to achieve
      cessation and/or reversal, is put into practice, using complementation of
      chemical species (isoflavones, anthraquinones, procyanidins, triterpenes,
      saponins and hydrogen sulphide prodrugs), thereby targeting multiple 'factors'.

PMID- 30195057
TI  - Aldosterone Mediated Regulation of Epithelial Sodium Channel (ENaC) Subunits in
      the Rat Hypothalamus.
AB  - Current evidence suggests that the epithelial Na+ channel (ENaC) in the brain
      plays a significant role in the development of hypertension. ENaC is present in
      vasopressin (VP) neurons in the hypothalamus, suggesting that ENaC in VP neurons
      is involved in the regulation of blood pressure. Our recent study demonstrated
      that high dietary salt intake caused an increase in the expression and activity
      of ENaC that were responsible for the more depolarized basal membrane potential
      in VP neurons. A known regulator of ENaC expression, the mineralocorticoid
      receptor (MR), is present in VP neurons, suggesting that ENaC expression in VP
      neurons is regulated by aldosterone. In this study, the effects of aldosterone
      and corticosterone on ENaC were examined in acute hypothalamic slices. Real-time
      PCR and Western blot analysis showed that aldosterone and corticosterone
      treatment resulted in a significant increase in the expression of gammaENaC, but
      not alpha- or betaENaC, and that this expression was attenuated by MR and
      glucocorticoid receptor (GR) antagonists. Moreover, chromatin immunoprecipitation
      demonstrated that the aldosterone-MR complex directly interacts with the promoter
      region of the gammaENaC gene. However, the treatment with aldosterone did not
      cause subcellular translocation of ENaC toward the plasma membrane nor an
      increase in ENaC Na+-leak current. These results indicate that expression of
      gammaENaC in VP neurons is induced by aldosterone and corticosterone through
      their MR and GR, respectively; however, aldosterone or corticosterone alone is
      not sufficient enough to increase ENaC current when they are applied to
      hypothalamic slices in vitro.

PMID- 30195059
TI  - Paeoniflorin extract reverses dexamethasone-induced testosterone over-secretion
      through downregulation of cytochrome P450 17A1 expression in primary murine theca
      cells.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Polycystic Ovarian Syndrome (PCOS) is a complex
      endocrine and reproductive disorder. A main hallmark includes increased androgen
      production. The root of Paeonia lactiflora Pall. (Bai Shao) is used in Chinese
      herbal medicine for reproductive disorders, however its effects and mechanisms on
      ovarian theca cells has not yet been fully elucidated. AIM OF THE STUDY: The aim
      of this study was to evaluate effect of paeoniflorin extract (PFE), the main
      constituents of Bai Shao, on androgen production in ovarian theca cells.
      MATERIALS AND METHODS: Primary murine theca cells were treated with
      concentrations of PFE (1-100 ug/mL) in the presence of dexamethasone (10 uM) with
      media-only treated cells used as the control. After 24 h, culture media was
      collected for biochemistry assays of testosterone and progesterone. Expression of
      key steroidogenic enzymes, cholesterol side-chain cleavage (CYP11A1) and 17alpha
      hydroxylase (CYP17A1) was characterized using immunofluorescence staining,
      immunoblotting and qRT-PCR. RESULTS: Dexamethasone significantly enhanced
      testosterone secretion (P < 0.05 vs. the control cells). PFE reversed over
      production of testosterone induced by dexamethasone in a dose-dependent manner.
      The treatment with PFE also normalized production of progesterone in
      dexamethasone-treated cells. Expression of CYP11A1 and CYP17A1 in the theca cells
      were visualised by immunofluorescence staining. All doses of PFE significantly
      inhibited CYP17A1 expression detected by immunoblotting, but only 100 ug/mL of
      PFE downregulated CYP11A1 expression and reduced CYP11A1 significantly in
      dexamethasone-treated theca cells. CONCLUSIONS: PFE may reduce over-secretion of
      testosterone in theca cells through downregulation of CYP17A1 and CYP11A1. These
      findings provide scientific evidence to treat ovarian hyperandrogenism with the
      root of Paeonia lactiflora Pall.

PMID- 30195060
TI  - Exposure to low concentration of fluoxetine affects development, behaviour and
      acetylcholinesterase activity of zebrafish embryos.
AB  - Fluoxetine (FLX) is a selective serotonin reuptake inhibitor (SSRI)
      antidepressant widely used in clinics and very often found in environmental
      samples of urban aquatic ecosystems in concentrations ranging from ng/L to MUg/L.
      Fish populations might be especially susceptible to FLX due to the presence of
      conserved cellular receptors of serotonin. Neurotoxic effects on fish biota of
      polluted water bodies may be expected, but there are no sufficient studies in the
      current literature to elucidate this hypothesis. Batteries of embryo larval
      assays with zebrafish were performed to evaluate the potential effects of FLX
      exposure, including environmentally relevant concentrations. Evaluated parameters
      included survival, development, behaviour and neuronal biochemical markers.
      Regarding acute toxicity, a 168 h-LC50 value of 1.18 mg/L was obtained. Moreover,
      hatching delay and loss of equilibrium were observed, but at a concentration
      level much higher than FLX measured environmental concentrations (>100 MUg/L). On
      the other hand, effects on locomotor and acetylcholinesterase activity (>=0.88
      and 6 MUg/L, respectively) were found at levels close to the maximum reported FLX
      concentration in surface waters. Altogether, these results suggest that FLX is
      neurotoxic to early life stages of zebrafish, in a short period of time causing
      changes in important ecological attributes which can probably be linked from
      molecular to population level.

PMID- 30195061
TI  - Pleurolophocercous and parapleurolophocercous types of cercariae: Revisiting
      concepts.

PMID- 30195063
TI  - Roles of ubiquitin in autophagy and cell death.
AB  - The balance between cell survival and cell death is often lost in human
      pathologies such as inflammation and cancer. Autophagy plays a critical role in
      cell survival: essential nutrients are generated by autophagy-dependent
      degradation and recycling of cellular garbage. On the other hand, cell death is
      induced by different programs, such as apoptosis, pyroptosis, and necroptosis.
      Emerging evidence is revealing how cell survival and cell death pathways are
      coordinated to determine cell fate. For instance, posttranslational modification
      of proteins with ubiquitin regulates many steps of autophagy and cell death
      pathways. In this review article, we will discuss how the ubiquitin system
      influences cell death and autophagy.

PMID- 30195062
TI  - The influence of maintenance therapy of rituximab on the survival of elderly
      patients with follicular lymphoma. A retrospective analysis from the database of
      the Czech Lymphoma Study Group.
AB  - The rituximab maintenance (RM) therapy for follicular lymphoma is effective and
      clinically well tolerated, however there is limited data regarding this from the
      elderly segment of the population. This analysis was performed to evaluate the
      efficacy of RM in elderly patients 65 years of age and older and to assess the
      influence of the induction therapy with immunochemotherapy (R-CHEMO) on the
      treatment outcome in a real world setting. A total of 232 consecutive patients
      treated with first-line R-CHEMO and RM (RM1 group; n = 158) or observation (RM0
      group; n = 74) were analyzed. The effect of which induction therapy (R-CHOP vs. R
      CVP) and the response of the patients to the first-line therapy were also
      evaluated. The addition of RM improved the treatment results in elderly patients.
      The 5- year overall survival rate in patients receiving R-CHEMO + RM1 compared to
      patients receiving R-CHEMO + RM0, was 83.7% (95% CI 76.1-89%) and 64.3% (95% CI
      51.8-74.3%), respectively, p = 0.0012. The induction therapy with R-CHOP was
      found to be more effective than R-CVP but it is necessary to point out higher age
      of patients in the R-CVP arm. The 5- year overall survival rate in patients using
      R-CHOP +/- RM and R-CVP +/- RM was 84.9% (95% CI 77.5-90%), and 65.0% (95% CI
      50.1-76.4%), respectively, p = 0.0008. The patients who achieved CR + uCR after
      having received first-line therapy had better outcomes compared to patients in
      PR. The 5- year overall survival rate in uCR + CR patients treated with R-CHEMO +
      RM1 and PR patients treated with R-CHEMO + RM1 was 90.6% and 68.3%, respectively,
      p = 0.0019. Rituximab maintenance treatment in patients 65 years and older
      yielded improved survival rates in a real world clinical setting. The R-CHOP
      regimen seems to be a more effective induction agent than R-CVP but the outcome
      of less intensively treated patients with R-CVP + RM is also acceptable. The
      achievement of uCR + CR after first-line therapy is associated with a better
      outcome.

PMID- 30195064
TI  - Sphingolipids modulate docking, Ca2+ sensitivity and membrane fusion of native
      cortical vesicles.
AB  - Docking, priming, and membrane fusion of secretory vesicles (i.e. regulated
      exocytosis) requires lipids and proteins. Sphingolipids, in particular,
      sphingosine and sphingosine-1-phosphate, have been implicated in the modulation
      of exocytosis. However, the specific exocytotic steps that sphingolipids modulate
      and the enzymes that regulate sphingolipid concentrations on native secretory
      vesicle membranes remain unknown. Here we use tightly coupled functional and
      molecular analyses of fusion-ready cell surface complexes and cortical vesicles
      isolated from oocytes to assess the role of sphingolipids in the late, Ca2+
      triggered steps of exocytosis. The molecular changes resulting from treatments
      with sphingolipid modifying compounds coupled with immunoblotting analysis
      revealed the presence of sphingosine kinase on native vesicles; the presence of a
      sphingosine-1-phosphate phosphatase is also indicated. Changes in sphingolipid
      concentrations on vesicles altered their docking/priming, Ca2+-sensitivity, and
      ability to fuse, indicating that sphingolipid concentrations are tightly
      regulated and maintained at optimal levels and ratios to ensure efficient
      exocytosis.

PMID- 30195065
TI  - Fresh red raspberry phytochemicals suppress the growth of hepatocellular
      carcinoma cells by PTEN/AKT pathway.
AB  - The red raspberry (Rubus idaeus L.) is a common fruit worldwide and its extract
      has been found to inhibit the growth of many types of tumors, mainly because it
      is rich in bioactive phytochemicals. However, the mechanism underlying its
      anticancer activity in hepatocellular carcinoma (HCC) is not well understood.
      Herein, the aim of this study was to determine the effects of red raspberry
      phytochemicals on the proliferation of hepatocellular carcinoma cells and to
      elucidate its biochemical and molecular targets. CCK8 and colony formation, as
      well as flow cytometry assays, were employed to determine the effects of red
      raspberry extract (RRE) on cell proliferation and cell cycle distribution in HCC
      cells. Our results showed that RRE significantly inhibited cell proliferation and
      arrested cell cycle progression at the S phase in HCC cells. RRE increased the
      expression of phosphatase and tensin homologue deleted on chromosome 10 (PTEN) by
      reducing the methylation status of the PTEN gene promoter and inhibiting DNMT1
      expression and regulated AKT signaling pathway. These findings show that red
      raspberry phytochemicals inhibit the proliferation of HCC cells by regulating
      PTEN/AKT signaling pathway, providing evidence that RRE may be used as a
      potential auxiliary therapy for patients with HCC.

PMID- 30195066
TI  - Reassessing the role of internalin B in Listeria monocytogenes virulence using
      the epidemic strain F2365.
AB  - OBJECTIVES: To investigate the contribution to virulence of the surface protein
      internalin B (InlB) in the Listeria monocytogenes lineage I strain F2365, which
      caused a deadly listeriosis outbreak in California in 1985. METHODS: The F2365
      strain displays a point mutation that hampers expression of InlB. We rescued the
      expression of InlB in the L. monocytogenes lineage I strain F2365 by introducing
      a point mutation in the codon 34 (TAA to CAA). We investigated its importance for
      bacterial virulence using in vitro cell infection systems and a murine
      intravenous infection model. RESULTS: In HeLa and JEG-3 cells, the F2365 InlB+
      strain expressing InlB was ~9-fold and ~1.5-fold more invasive than F2365,
      respectively. In livers and spleens of infected mice at 72 hours after infection,
      bacterial counts for F2365 InlB+ were significantly higher compared to the F2365
      strain (~1 log more), and histopathologic assessment showed that the F2365 strain
      displayed a reduced number of necrotic foci compared to the F2365 InlB+ strain
      (Mann-Whitney test). CONCLUSIONS: InlB plays a critical role during infection of
      nonpregnant animals by a L. monocytogenes strain from lineage I. A spontaneous
      mutation in InlB could have prevented more severe human morbidity and mortality
      during the 1985 California listeriosis outbreak.

PMID- 30195067
TI  - Association of filaggrin gene mutations and childhood eczema and wheeze with
      phthalates and phosphorus flame retardants in house dust: The Hokkaido study on
      Environment and Children's Health.
AB  - BACKGROUND AND AIM: Exposure to phthalates and phosphorus flame retardants (PFRs)
      is considered to be a risk factor for asthma and allergies. However, little is
      known about the contribution of loss-of-function mutations in the gene encoding
      filaggrin (FLG) gene, which are considered to be predisposing factors for eczema
      and asthma, to these associations. We investigated the associations between
      exposure to phthalates and PFRs in dust and eczema/wheeze among Japanese
      children, taking into consideration loss-of-function mutations in FLG. METHODS:
      This study was part of the Hokkaido study on Environment and Children's Health.
      Seven phthalates and 11 PFRs in household dust were measured by gas
      chromatography-mass spectrometry. Eczema and wheeze were assessed in children
      aged 7 years using the International Study of Asthma and Allergies in Childhood
      questionnaire. Eight FLG mutations previously identified in the Japanese
      population were extracted from cord blood samples. Children with one or more FLG
      mutations were considered to be positive for FLG mutations. The study included
      296 children who had complete data (birth records, FLG mutations, first trimester
      and 7 years questionnaires, and phthalate/PFR levels). Odds ratios (ORs) and 95%
      confidential intervals (CIs) of eczema and wheeze were calculated for log
      transformed phthalate/PFR levels by logistic regression. We also performed
      stratified analyses based on FLG mutations. RESULTS: The prevalence rates of
      eczema and wheeze were 20.6% and 13.9%, respectively. Among children without any
      FLG mutations, tris (1, 3-dichloro-2-propyl) phosphate (TDCIPP) increased the OR
      of wheeze, (OR: 1.22, CI: 1.00-1.48). Significant p values for trends were found
      between tris (2-butoxyethyl) phosphate (TBOEP) and eczema and di-iso-nonyl
      phthalate (DiNP) and eczema among children without any FLG mutations,
      respectively. CONCLUSIONS: Despite our limited sample size and cross-sectional
      study design, the effects of indoor environmental factors on childhood eczema and
      wheeze were clearer in children without loss-of-function mutations in FLG than in
      children with mutations. Children with FLG mutations might already be cared for
      differently in terms of medication or parental lifestyle. Further studies in
      larger populations are warranted so that severity of symptoms and combinations of
      FLG mutations can be investigated.

PMID- 30195068
TI  - Comparative analysis of five Mucor species transcriptomes.
AB  - Mucor species belong to the Mucorales order within the Mucoromycota phylum, an
      early diverging fungal lineage. Although Mucor species are often ubiquitous some
      species have been reported to specifically occur in certain ecological niches. In
      this study, similarities and differences of a representative set of Mucor species
      with contrasted lifestyles were investigated at the transcriptome level. Five
      strains pertaining to five different species were studied, namely M. fuscus and
      M. lanceolatus, two species used in cheese production (during ripening), M.
      racemosus, a recurrent cheese spoiler sometimes described as an opportunistic
      pathogen, M. circinelloides, often described as an opportunistic pathogen and M.
      endophyticus, a plant endophyte. A core transcriptome was delimited and a
      phylogenetic analysis led to an altered phylogenetic placement of M. endophyticus
      compared to previously published topologies. Interestingly, the core
      transcriptome comprising 5566 orthogroups included genes potentially involved in
      secondary metabolism. As expected, given the wide taxonomic range investigated,
      the five transcriptomes also displayed specificities that can be, for some of
      them, linked to the different lifestyles such as differences in the composition
      of transcripts identified as virulence factors or carbohydrate transporters.

PMID- 30195069
TI  - Phylogenetic analysis of protein sequences based on a novel k-mer natural vector
      method.
AB  - Based on the k-mer model for protein sequence, a novel k-mer natural vector
      method is proposed to characterize the features of k-mers in a protein sequence,
      in which the numbers and distributions of k-mers are considered. It is proved
      that the relationship between a protein sequence and its k-mer natural vector is
      one-to-one. Phylogenetic analysis of protein sequences therefore can be easily
      performed without requiring evolutionary models or human intervention. In
      addition, there exists no a criterion to choose a suitable k, and k has a great
      influence on obtaining results as well as computational complexity. In this
      paper, a compound k-mer natural vector is utilized to quantify each protein
      sequence. The results gotten from phylogenetic analysis on three protein datasets
      demonstrate that our new method can precisely describe the evolutionary
      relationships of proteins, and greatly heighten the computing efficiency.

PMID- 30195070
TI  - Novel dual functional monomers based molecularly imprinted polymers for selective
      extraction of myricetin from herbal medicines.
AB  - Herein, novel dual functional monomers based molecularly imprinted polymers
      (MIPs) were successfully prepared and used to extract myricetin from Carthamus
      tinctorius L., also named safflower (family, Compositae) and the flower of
      Abelmoschus manihot (Linn.) Medicus (family, Malvaceae). The polymers were
      prepared using myricetin as template, 4-vinylpyridine (4-VP) and glycidyl
      methacrylate (GMA) as dual functional monomers, ethylene glycol dimethyl acrylate
      (EGDMA) as cross-linker and methanol-acetonitrile (1:2, v/v) as solvent,
      respectively. Fourier transform infrared spectroscopy (FT-IR) and scanning
      electron microscopy (SEM) were applied to characterize the polymers. Further, the
      adsorption and selectivity experiments of MIPs were evaluated. The results
      revealed that MIPs showed high adsorption ability and selectivity toward
      myricetin. Finally, MIPs were employed as adsorbents for solid phase extraction
      (SPE) of myricetin from safflower and the flowers of A. manihot (Linn.) Medicus.
      Further analysis was conducted by using high performance liquid chromatography
      diode array detection (HPLC-DAD). The recovery of mrricetin in safflower and in
      the flowers of A. manihot ranged from 79.82% to 83.91%, 81.50% to 84.32%,
      respectively. These results indicated that MIPs can be applied to the extraction
      and separation of myricetin from various complex matrixes.

PMID- 30195071
TI  - Fast high-throughput screening of glutathione S-transferase polymorphism by
      voltage programming-based multi-channel microchip electrophoresis.
AB  - Glutathione S-transferase (GST) polymorphism (M1 = 215 bp and T1 = 480 bp) can
      cause liver damage and increase the risk of cancer. In this study, voltage
      programming (VP)-based microchip electrophoresis (ME) with a laser-induced
      fluorescence (LIF) detector was developed to detect specific sizes of DNA
      fragments. The optimum conditions for a single-channel microchip were as follows:
      4 kV for 0-9.5 s, 1.5 kV for 9.5-15.5 s, and 4 kV for 15.5-30 s. Next, these
      conditions were applied to another microchip that was constructed with many
      channels making possible simultaneous parallel detection. Finally, GST genes
      extracted from human blood were amplified by polymerase chain reaction (PCR) and
      were introduced into the multi-channel microchip. Target DNA molecules amplified
      by only 10 PCR cycles could be detected by the VP-based multi-channel ME method,
      but not by slab gel electrophoresis (SGE). In addition, the migration time for ME
      was <15 s, which was 700 times faster than conventional SGE. The developed VP
      based multi-channel ME method with LIF detection was demonstrated to be an
      effective, rapid analysis technique for highly sensitive and high-throughput
      screening of GST genes.

PMID- 30195073
TI  - Significant Nationwide Variability in the Costs and Hospital Mortality Rates of
      Autologous Stem Cell Transplantation for Multiple Myeloma: An Analysis of the
      Nationwide Inpatient Sample Database.
AB  - Autologous hematopoietic stem cell transplantation (AHCT) is the standard of care
      for eligible patients with multiple myeloma (MM). In this study, we explored
      disparities in hospital cost and in-hospital mortality among patients with MM who
      underwent AHCT. Data were obtained from the Nationwide Inpatient Sample database
      for 2005 to 2014. International Classification of Diseases, Ninth Edition,
      Clinical Modification diagnosis and procedure codes were used to identify
      patients. Hospitals were divided into quintiles according to the weighted volume
      of AHCTs performed in patients with MM. Multiple imputation with chained equation
      was used for missing data. Linear trend analysis of age- and sex-adjusted
      mortality, as well as inflation-adjusted hospital cost, was performed. Univariate
      regression screening followed by stepwise multivariate regression was performed
      for dependent variables, including mortality and inflation-adjusted hospital
      cost. Identified significant predictors underwent sensitivity analyses. Overall
      age- and sex-adjusted mortality rates and inflation-adjusted hospital costs
      decreased between 2005 and 2014; however, tremendous nationwide variability
      exists. Patients who underwent AHCT at very-low-volume hospitals (Q1) had
      significantly higher in-hospital mortality. Both geographic location and hospital
      type had impacted age- and sex-adjusted mortality rates and inflation-adjusted
      hospital costs. Despite an overall improvement in mortality and decreased cost of
      AHCT for patients with MM, nationwide variability in care exists. Further study
      is needed to identify correctable factors that contribute to the identified
      correlation.

PMID- 30195072
TI  - Preliminary evaluation of a novel 18F-labeled PARP-1 ligand for PET imaging of
      PARP-1 expression in prostate cancer.
AB  - INTRODUCTION: Poly (ADP-ribose) polymerase-1 (PARP-1) plays many roles in
      prostate cancer (PC), such as mediating DNA damage repair, transcriptional
      regulation and nuclear hormone receptor signaling. Because of this, PARP-1 has
      been targeted for therapy in PC, and non-invasive imaging of PARP-1 could help
      predict which patients are likely to respond to such therapy. Several PARP-1
      positron emission tomography (PET) imaging agents have been developed and show
      promise for imaging PARP-1 expression in breast, brain, and lung cancer in small
      animals, but not as yet in prostate cancer. [18F]WC-DZ-F is an analogue of
      [18F]FluorThanatrace (FTT) and [125I]KX1, which are well-established PARP-1
      ligands for measuring PARP-1 expression. Herein, we evaluated the potential of
      [18F]WC-DZ-F for the imaging PARP-1 expression in PC. METHODS: [18F]WC-DZ-F was
      synthesized by a two-step sequence. [18F]WC-DZ-F was evaluated by in vitro uptake
      studies in PC-3 cells and by in vivo biodistribution and microPET imaging using
      PC-3 tumor xenografts. Ex vivo autoradiography of PC-3 tumors after microPET
      imaging was also performed. RESULTS: [18F]WC-DZ-F has high, PARP-1-specific
      uptake in PC-3 cells. In the microPET imaging study, [18F]WC-DZ-F accumulated in
      PC-3 xenograft tumors over 2 h, and the uptake was significantly reduced by
      blocking with olaparib. PC-3 tumors were clearly visualized in microPET images,
      and the imaging results were further confirmed by autoradiography of PC-3 tumors
      ex vivo. In the biodistribution study [18F]WC-DZ-F washed out quickly from most
      tissues within 2 h, except for the liver in which the uptake was not blockable by
      olaparib. CONCLUSIONS: We synthesized a novel PARP-1 radioligand, [18F]WC-DZ-F.
      The preliminary evaluation of [18F]WC-DZ-F indicates that it is a suitable PET
      imaging agent for measuring PARP-1 expression in prostate cancer and should be
      applicable to other types of cancers.

PMID- 30195074
TI  - Significant Risk of Graft-versus-Host Disease with Exposure to Checkpoint
      Inhibitors before and after Allogeneic Transplantation.
AB  - Investigators are using checkpoint inhibitors (CPIs) to treat aggressive
      hematologic malignancies in patients undergoing allogeneic hematopoietic stem
      cell transplantation (allo-HSCT) and in some patients with relapsed disease after
      allo-HSCT. CTLA-4 inhibitors and PD-1 inhibitors are 2 main types of CPIs, which
      work through activation of the immune system. On one hand, CPIs can achieve graft
      versus-tumor effect, and on the other hand, there is a risk of graft-versus-host
      disease (GVHD). After a comprehensive literature review, we included data (n =
      283) from 24 studies (11 original manuscripts and 13 case reports or case series)
      and evaluated the results to assess the safety and efficacy of CPI use in
      conjunction with allo-HSCT. Among the 283 patients, 107 received CPI before allo
      HSCT, and 176 received CPI after allo-HSCT. The most common indication for CPI
      use was for Hodgkin lymphoma. The CPIs used in various studies included
      ipilimumab, nivolumab, and pembrolizumab. Among the patients exposed to CPI
      before allo-HSCT, 56% developed acute GVHD and 29% developed chronic GVHD.
      Investigators reported 20 deaths, 60% of which were GVHD-related. The overall
      mortality risk with GVHD is 11%. In this group, investigators noted an objective
      response rate (ORR) in 68% of patients, with complete remission (CR) in 47%,
      partial remission (PR) in 21%, and stable disease in 11%. Among the patients who
      received a CPI after allo-HSCT for disease relapse, 14% developed acute GVHD and
      9% developed chronic GVHD. Investigators reported 40 deaths, 28% of which were
      GVHD-related. The mortality risk with GVHD is approximately 7%. Investigators
      reported ORR in 54% of patients, with CR in 33%, PR in 21%, and disease
      stabilization in 5%. After careful evaluation of collective data, we found that
      CPI use both before and after allo-HSCT can be highly effective, but exposure can
      lead to a significantly increased risk of GVHD-related morbidity and mortality in
      this patient population. Despite limited availability of data, there is need for
      extreme caution while making decisions regarding the use of CPIs. Detailed
      discussions and prospective well-designed clinical trials are needed to explore
      this issue further.

PMID- 30195076
TI  - Ponatinib evaluation and safety in real-life chronic myelogenous leukemia
      patients failing more than two tyrosine kinase inhibitors: the PEARL
      observational study.
AB  - Ponatinib represents a remarkable progress in the treatment of heavily pretreated
      chronic myelogenous leukemia (CML) and de novo Philadelphia chromosome-positive
      ALL patients despite significant toxicity in clinical trials. To date, "real
      life" data remain few and the use of ponatinib in this setting and its
      consequences remain mostly unknown. We report, within a national observational
      study, the use of ponatinib in unselected CML patients who had previously failed
      >=2 lines of tyrosine kinase inhibitor (TKI) therapy (or one line if an Abelson
      (ABL)T315I mutation was identified), in real-life conditions (2013-2014) in a
      compassionate program. Our analysis has been focused on 48 chronic phase CML
      patients recorded. With a median follow-up of 26.5 months since ponatinib
      initiation, the overall survival (OS) rates (80.5% at 3 years) and cumulative
      incidence of major molecular response (81.8% at 18 months) were similar to those
      of the phase II study, with no influence of BCR-ABL mutations nor the reason of
      ponatinib prescription. A specific subanalysis of the preexisting cardiovascular
      risk factors and events occurring on ponatinib is described. These events
      occurred after a median time on ponatinib of 5.8 months (excluding hypertension)
      and were observed in 29/48 patients (47%), even in those already on anti
      aggregants/coagulants. The majority were not severe and resolved, but two cases
      were fatal. Other hematological or nonhematological nonvascular adverse events
      were similar to those previously described in trials. This observational study
      reports similar rates of survival, molecular responses, and a slight increase in
      the cardiovascular toxicity of ponatinib in real-life conditions, prompting
      improved control of cardiovascular risk factors and selection of patients.

PMID- 30195077
TI  - miR-217 sensitizes chronic myelogenous leukemia cells to tyrosine kinase
      inhibitors by targeting pro-oncogenic anterior gradient 2.
AB  - BCR-ABL1-independent mechanisms had been thought to mediate drug resistance to
      tyrosine kinase inhibitors (TKIs) in patients with chronic myelogenous leukemia
      (CML). The pro-oncogenic anterior gradient 2 (AGR2) mediates drug resistance of
      cancer cells. In this study, we observed an increased level of AGR2 in TKI
      resistant CML cells. Silence of AGR2 in dasatinib-resistant K562 (K562DR) cells
      led to restored sensitivity to dasatinib both in vitro and in vivo. Exposure to
      dasatinib induced upregulation of AGR2 in K562 cells, which indicated a probable
      treatment-related drug resistance. We further investigated the potential
      interaction between microRNA (miRNA) and AGR2 in K562DR cells and found that
      downregulation of miR-217 was associated with overexpression of AGR2 in K562DR
      cells. Luciferase reporter assay identified that miR-217 negatively regulated
      expression of AGR2 through binding the 3'-untranslated region of AGR2.
      Hypermethylation of the CpG island on the promoter region of the MIR217 gene is a
      probable reason for the downregulation of miR-217 in dasatinib-treated K562
      cells. Forced expression of miR-217 led to decreased expression of AGR2 as well
      as compromised TKI-resistant potential of K562DR cells. Similarly, overexpression
      of miR-217 resensitized K562DR cells to dasatinib treatment in a murine xenograft
      transplantation model. TKI treatment-induced drug resistance is correlated with a
      decrease of miR-217 and upregulation of AGR2. The miR-217/AGR2 interaction might
      be a potential therapeutic target in treating CML patients with TKI resistance.

PMID- 30195075
TI  - Motor neuron loss and neuroinflammation in a model of alpha-synuclein-induced
      neurodegeneration.
AB  - Mechanisms underlying alpha-synuclein (alphaSyn) mediated neurodegeneration are
      poorly understood. Intramuscular (IM) injection of alphaSyn fibrils in human A53T
      transgenic M83+/- mice produce a rapid model of alpha-synucleinopathy with highly
      predictable onset of motor impairment. Using varying doses of alphaSyn seeds, we
      show that alphaSyn-induced phenotype is largely dose-independent. We utilized the
      synchrony of this IM model to explore the temporal sequence of alphaSyn
      pathology, neurodegeneration and neuroinflammation. Longitudinal tracking showed
      that while motor neuron death and alphaSyn pathology occur within 2 months post
      IM, astrogliosis appears at a later timepoint, implying neuroinflammation is a
      consequence, rather than a trigger, in this prionoid model of synucleinopathy.
      Initiating at 3 months post IM, immune activation dominates the pathologic
      landscape in terminal IM-seeded M83+/- mice, as revealed by unbiased
      transcriptomic analyses. Our findings provide insights into the role of
      neuroinflammation in alphaSyn mediated proteostasis and neurodegeneration, which
      will be key in designing potential therapies.

PMID- 30195078
TI  - Robotic Radical Hysterectomy for Cervical Cancer: A Population-Based Study of
      Adoption and Immediate Postoperative Outcomes in the United States.
AB  - STUDY OBJECTIVE: To compare the use of robotic radical hysterectomy (RRH) and
      abdominal radical hysterectomy (ARH) in the United States, with secondary
      outcomes of perioperative complications, hospital length of stay (LOS), immediate
      postoperative mortality, cost and a subanalysis compared with laparoscopic
      radical hysterectomy (LRH). DESIGN: Retrospective cohort study (Canadian Task
      Force classification II-2). SETTING: Data from the National Inpatient Sample
      (NIS), a government-funded database of hospitalization in the United States.
      PATIENTS AND INTERVENTIONS: All women with cervical cancer undergoing RH between
      2008 and 2015 in the United States and included in the NIS database. MEASUREMENTS
      AND MAIN RESULTS: Trends in surgical modality, baseline characteristics, LOS,
      perioperative outcomes, mortality, and hospital charges were compared between RRH
      and ARH. Regression models were adjusted for baseline characteristics. Among
      41,317 women with cervical cancer, 3563 underwent RH, including 21.0% with a
      robotic procedure, 6.5% with a laparoscopic procedure, and 72.5% with open
      surgery. The annual rates of ARH declined significantly over the study period,
      whereas those of RRH increased. Baseline characteristics were comparable between
      the RRH and ARH groups. Compared with the ARH group, women undergoing RRH had a
      lower rate of cumulative postoperative complications (18.16% vs 21.21%; odds
      ratio [OR], 0.81; 95% confidence interval [CI], 0.6-1.0; p = .05), including
      lower rates of wound infection (0.27% vs 1.82%; OR, 0.14; 95% CI, 0.03-0.6; p <
      .01), sepsis (0.27% vs 1.20%; OR, 0.22; 95% CI, 0.05-0.9; p = .03), fever (1.87%
      vs 4.06%; OR, 0.44, 95% CI, 0.3-0.8; p < .01), and ileus (2.8% vs 9.13%; OR,
      0.28; 95% CI, 0.12-0.4; p < .01). The LOS was significantly shorter in the RRH
      group (median, 2days vs 4 days; p < .01). The total median hospitalization charge
      was $47,218 for the RRH group, compared with $38,877 for the ARH group (p < .01).
      CONCLUSION: RRH is being increasingly performed in the United States and is
      associated with shorter LOS and less postoperative morbidity; however, long-term
      oncologic outcomes require additional attention.

PMID- 30195079
TI  - Preserving fertility by treating the three compartments: laparoscopic approach to
      deep infiltrating endometriosis.
AB  - STUDY OBJECTIVE: To describe a laparoscopic technique for the resection of deep
      endometriosis, treating the three compartments. DESIGN: Educational video
      SETTING: Tertiary referral center in Strasbourg, France PATIENTS: This is the
      case of a 37-year-old primiparous woman. Her main symptoms included dysmenorrhea
      and dyspareunia associated with pollakiuria and macroscopic menstrual hematuria
      (with emission of endometriotic tissue on analysis). She also complained of
      dyschezia. The MRI revealed an endometriotic nodule in the vesicouterine space
      with an involvement of the anterior wall of the uterus and a suspicion of bladder
      adenomyosis. There are lateral spicules attracting the ovaries towards the
      midline and an infiltration of the round ligaments and nodules related to the
      rectovaginal space's endometriosis. A possible invasion is noted underneath the
      rectal mucosa. The patient wants to preserve her fertility. INTERVENTION:
      Adenomyomectomy, partial cystectomy, and bowel resection. Fertility preservation
      is mandatory due to the patient's desire for future pregnancy. The local
      institutional review board has approved the video. MEASUREMENTS AND MAIN RESULTS:
      Initially, an ultrasonography was performed showing the adenomyoma invading the
      bladder. The second step was a cystoscopic evaluation by means of a double J
      probe and a bladder catheter. After the surgery, the bladder catheter was left in
      place for 15 days and the double J stents for 6 weeks. The first step is the
      dissection of the vesicouterine space to dissect the anterior adenomyoma from the
      bladder. A partial cystectomy is then performed to remove the bladder nodule. The
      adenomyoma is resected at its uterine portion and the uterus is sutured. Surgery
      is then performed in the posterior compartment. Ureterolysis is performed
      bilaterally, and the pararectal fossas are then opened. The rectovaginal space is
      dissected. A rectosigmoid resection is mandatory to remove the bowel nodule.
      Patient follow-up included regular consultations and a hysterosonography at 6
      weeks after surgery. Hysterosonography demonstrated an adequate patency. No
      adhesions to the uterus were found. We recommended to wait for 6 months to allow
      pregnancy according to the department's protocols. A clinical improvement was
      observed. Today at 8 months, she has not attempted to be pregnant again.
      CONCLUSION: A complete surgery is feasible for severe and deep endometriosis with
      a multicompartmental disease, using a laparoscopic approach aiming to preserve
      fertility.

PMID- 30195080
TI  - Manufacturing and characterization of long-acting levonorgestrel intrauterine
      systems.
AB  - Mirena(r) is long-acting (5 years) contraceptive intrauterine device. It is
      composed of a hollow cylindrical drug reservoir (containing Levonorgestrel and
      polydimethylsiloxane), which is covered with a release rate controlling silicone
      membrane. This structure presents a manufacturing challenge and to date, there
      have been no literature reports on the manufacturing, product design and quality
      evaluation of these hollow cylindrical intrauterine devices. It is vital to
      develop a reproducible and robust manufacturing process for these long-acting
      intrauterine devices or systems to obtain an understanding the in vitro and in
      vivo performance of such drug-device combinations. In this study, a twin-syringe
      method with a customized mold was developed to manufacture hollow cylindrical
      polydimethylsiloxane (PDMS)-based levonorgestrel intrauterine systems (LNG-IUSs).
      Different mold materials, curing temperatures and times were screened to
      fabricate PDMS-drug reservoirs with good quality characteristics (easy demolding,
      good appearance and appropriate physicochemical characteristics). The prepared
      PDMS-drug reservoirs were covered with the release rate controlling membrane to
      fabricate the LNG-IUSs. Physicochemical characterization (drug content and
      content uniformity, powder X-Ray diffraction (PXRD), differential scanning
      calorimetry (DSC), thermogravimetric analysis (TGA) and Fourier-transform
      infrared spectroscopy (FTIR) of the PDMS-drug reservoirs with different drug
      loadings (10%, 25% and 50% w/w) was conducted. Real-time in vitro drug release
      testing of LNG-IUSs with different drug loading was performed in normal saline
      (0.9% w/v NaCl) at 37  degrees C using a water bath shaker rotating at 100 rpm.
      The prepared PDMS-drug reservoirs demonstrated good and reproducible quality
      characteristics including appearance (smooth surfaces), targeted drug loading and
      good drug content uniformity in the PDMS matrix. The PXRD showed that the
      crystallinity of the API was maintained inside the PDMS matrix. DSC, TGA and FTIR
      confirmed the structure of the drug and the PDMS, indicating no interaction
      between the drug and the PDMS matrix in the prepared LNG-IUSs. Real-time in vitro
      drug release from the LNG-IUSs with different drug loadings showed zero-order
      release kinetics, and the drug release rate (based on daily release percentage)
      was inversely proportional to the drug loading.

PMID- 30195081
TI  - Investigation on the impact of powder arching in small die filling.
AB  - The flow of particulate materials is critical during processes such as mixing,
      compression and packing. Non-cohesive arching, a feature characteristic of coarse
      and free-flowing particles, has been studied extensively for silos and hoppers.
      However, the arching of powders during die fill has received much less attention.
      In this study, die fill performance of coarse and free-flowing nonpareils was
      evaluated using a specially designed die filling device in order to investigate
      the impact of non-cohesive arching during die fill under gravity flow. Through
      evaluating die fill performance, the arching phenomenon during dynamic conditions
      of die fill could be captured. Nonpareils with large particle size increased the
      likelihood of arching and caused poorer die fill performance for narrow orifices.
      In contrast, die fill in large orifices was generally better with larger
      particles due to reduced inter-particulate friction. Both particle size and size
      distribution influenced non-cohesive arching during die fill. Forced feeding did
      not appear to affect die fill performance and non-cohesive arching. A critical
      particle size range beyond which die fill performance would decrease,
      particularly for the narrow orifices, was identified. Findings from this study
      provided a better insight into non-cohesive arching during die fill.

PMID- 30195082
TI  - Vaginal Bifidobacterium breve for preventing urogenital infections: Development
      of delayed release mucoadhesive oral tablets.
AB  - Bifidobacteria are predominant microorganisms in the intestinal flora, but at the
      same time represent a subdominant group of the vaginal microbiota. For this
      reason, oral administration of these probiotic bacteria can provide beneficial
      effect for both intestinal and urogenital ecosystems. The first aim of this study
      was to test the strain Bifidobacterium breve BC204, isolated from a vaginal swab
      of a healthy woman, for its capability to adhere to human cells, to survive to
      gastric acids and bile salts and to exert antimicrobial activities. The second
      aim of the work was to develop an oral formulation able to guarantee bacterial
      survival during storage and administration, thus favouring intestinal and vaginal
      colonization. B. breve BC204 was encapsulated by spray-drying and subsequently
      formulated in time-dependent erodible tablets. B. breve BC204 showed good ability
      to adhere to Caco-2 cells and moderate ability to resist to gastrointestinal
      stress. Moreover, it exerted a strong antimicrobial activity against urogenital
      and enteric pathogens. Microencapsulation followed by tablet production allowed
      high loading and survival of B. breve BC204, associated to a delayed release and
      mucoadhesive ability. These characteristics are required to achieve appropriate
      amount and persistence of viable microbial cells in the treatment site.

PMID- 30195084
TI  - Osteogenesis by foamed and 3D-printed nanostructured calcium phosphate scaffolds:
      Effect of pore architecture.
AB  - There is an urgent need of synthetic bone grafts with enhanced osteogenic
      capacity. This can be achieved by combining biomaterials with exogenous growth
      factors, which however can have numerous undesired side effects, but also by
      tuning the intrinsic biomaterial properties. In a previous study, we showed the
      synergistic effect of nanostructure and pore architecture of biomimetic calcium
      deficient hydroxyapatite (CDHA) scaffolds in enhancing osteoinduction, i.e.
      fostering the differentiation of mesenchymal stem cells to bone forming cells.
      This was demonstrated by assessing bone formation after implanting the scaffolds
      intramuscularly. The present study goes one step forward, since it analyzes the
      effect of the geometrical features of the same CDHA scaffolds, obtained either by
      3D-printing or by foaming, on the osteogenic potential and resorption behaviour
      in a bony environment. After 6 and 12 weeks of intraosseous implantation, both
      bone formation and material degradation had been drastically affected by the
      macropore architecture of the scaffolds. Whereas nanostructured CDHA was shown to
      be highly osteoconductive both in the robocast and foamed scaffolds, a superior
      osteogenic capacity was observed in the foamed scaffolds, which was associated
      with their higher intrinsic osteoinductive potential. Moreover, they showed a
      significantly higher cell-mediated degradation than the robocast constructs, with
      a simultaneous and progressive replacement of the scaffold by new bone. In
      conclusion, these results demonstrate that the control of macropore architecture
      is a crucial parameter in the design of synthetic bone grafts, which allows
      fostering both material degradation and new bone formation. Statement of
      Significance 3D-printing technologies open new perspectives for the design of
      patient-specific bone grafts, since they allow customizing the external shape
      together with the internal architecture of implants. In this respect, it is
      important to design the appropriate pore geometry to maximize the bone healing
      capacity of these implants. The present study analyses the effect of pore
      architecture of nanostructured hydroxyapatite scaffolds, obtained either by 3D
      printing or foaming, on the osteogenic potential and scaffold resorption in an in
      vivo model. While nanostructured hydroxyapatite showed excellent osteoconductive
      properties irrespective of pore geometry, we demonstrated that the spherical,
      concave macropores of foamed scaffolds significantly promoted both material
      resorption and bone regeneration compared to the 3D-printed scaffolds with
      orthogonal-patterned struts and therefore prismatic, convex macropores.

PMID- 30195083
TI  - PEGylation of model drug carriers enhances phagocytosis by primary human
      neutrophils.
AB  - : Targeted drug carriers are attractive for the delivery of therapeutics directly
      to the site of a disease, reducing systemic side effects and enhancing the
      efficacy of therapeutic molecules. However, the use of particulate carriers for
      drug delivery comes with its own set of challenges and barriers. Among these, a
      great deal of research effort has focused on protecting carriers from clearance
      by phagocytes via altering carrier surface chemistry, mostly with the use of
      polyethylene glycol (PEG) chain coatings. However, few papers have explored the
      effects of PEGylation on uptake by freshly-obtained primary human phagocytes in
      physiological conditions. In this work, we investigate the effect of PEGylation
      on particle uptake by primary human neutrophils in vitro and compare these
      effects to several cell lines and other model phagocytic cells systems. We find
      that human neutrophils in whole blood preferentially phagocytose PEGylated
      particles (e.g., ~40% particle positive neutrophils for PEGylated versus ~20% for
      carboxylated polystyrene microspheres) and that this effect is linked to factors
      present in human plasma. Model phagocytes internalized PEGylated particles less
      efficiently or equivalently to carboxylated particles in culture medium but
      preferentially phagocytosed PEGylated particles in the human plasma (e.g., ~86%
      versus ~63% PEGylated versus carboxylated particle positive cells, respectively).
      These findings have significant implications for the efficacy of PEGylation in
      designing long-circulating drug carriers, as well as the need for thorough
      characterization of drug carrier platforms in a wide array of in vitro and in
      vivo assays. STATEMENT OF SIGNIFICANCE: The work in this manuscript is highly
      significant to the field of drug delivery, as it explores in-depth the effects of
      polyethylene glycol (PEG) coatings, which are frequently used to prevent
      phagocytic clearance of particulate drug carriers, on the phagocytosis of such
      carriers by neutrophils, the most abundant leukocyte in blood circulation.
      Surprisingly, we find that PEGylation enhances uptake by primary human
      neutrophils, specifically in the presence of human plasma. This result suggests
      that PEGylation may not confer the benefits in humans once thought, and may help
      to explain why PEG has not become the "magic bullet" it was once thought to be in
      the field of particulate drug delivery.

PMID- 30195085
TI  - Hydration mechanism of a calcium phosphate cement modified with phytic acid.
AB  - Calcium phosphate cements composed of beta-tricalcium phosphate (beta-TCP) and
      phosphoric acid were modified by addition of 5, 10, 12.5, 15 and 20 wt% phytic
      acid (IP6) related to the beta-TCP content and compared to a reference containing
      0.5 M citric acid monohydrate solution as setting regulator. The hydration
      reaction of these cements was investigated by isothermal calorimetry and in-situ
      X-ray diffraction at 23  degrees C and 37  degrees C. The cements were further
      characterized with respect to their injectability, rheology, zeta potential and
      time-resolved compressive strength development. Injectability was strongly
      improved by IP6 addition, while the maximum effect was already reached by the
      addition of 5 wt% IP6. This could be clearly related to an increase of the
      negative zeta potential leading to a mutual repulsion of cement particles. A
      further increase of the IP6 content had a detrimental effect on initial paste
      viscosity and shifted the gelation point to earlier time points. IP6 was further
      proven to act as a retarder for the cement setting reaction, whereas the effect
      was stronger for higher IP6 concentrations. Additionally, IP6 favoured the
      formation of monetite instead of brushite and a better mechanical performance
      compared to the IP6 free reference cement. STATEMENT OF SIGNIFICANCE: Calcium
      phosphate cements (CPCs) are clinically applied for bone repair due to their
      excellent biocompatibility and bone regeneration capacity. A deep understanding
      of the setting mechanism is the prerequisite for the targeted fabrication and
      application of such bone cements, whereas setting characteristics are usually
      adjusted by additives. Here, novel injectable CPC formulations were developed by
      modifying a cement composed of beta-tricalcium phosphate and phosphoric acid with
      phytic acid (IP6). A detailed investigation of the setting mechanism of the IP6
      modified CPCs is provided, which demonstrated the effectiveness of IP6 as setting
      regulator to adjust the reaction time and kind of setting product. Additionally,
      the high surface charge of cement particles after IP6 addition was effective in
      dispersing cement particles leading to low viscous cement pastes, which can be
      directly applied through a syringe for minimal invasive surgery.

PMID- 30195087
TI  - Bifunctional magnetic nanoparticles for efficient cholesterol detection and
      elimination via host-guest chemistry in real samples.
AB  - Cholesterol is an essential compound for maintaining cellular homeostasis and
      human healthy. Sensitive detection of cholesterol and efficient elimination of
      excess cholesterol have become the essential manipulations in clinical diagnosis
      and health management. To date, it is still quite challenging that cholesterol
      detection and elimination tasks are carried out simultaneously. In this study,
      bifunctional magnetic nanoparticles (Fe3O4@PDA-PBA-CD) are designed and
      fabricated to overcome this difficulty. Taking advantages of competitive host
      guest interaction and magnetic separation, highly efficient, reusable and
      simultaneous cholesterol detection and elimination can be achieved. The limit of
      detection is determined to be 4.3 nM, which is comparable or even lower than
      existing methods. The distinguished performance may attribute to the high loading
      efficiency and magnetic enrichment of nanoparticles. Besides, this efficient
      strategy is resistant to interfering substances, thus realizing sensitive
      cholesterol detection in real sample. Simultaneously, the bifunctional magnetic
      nanoparticles also have up to 95% cholesterol elimination efficiency, which is
      higher than previous reported methods. Furthermore, the nanoparticles are turned
      out to be reusable within 5 times without noticeable loss in cholesterol
      elimination efficiency. Therefore, the bifunctional magnetic nanoparticles
      fabricated here could hold great potential for simultaneous cholesterol detection
      and elimination in practical applications.

PMID- 30195088
TI  - Assessment of muscular energy metabolism and heat shock response of the green
      abalone Haliotis fulgens (Gastropoda: Philipi) at extreme temperatures combined
      with acute hypoxia and hypercapnia.
AB  - The interaction between ocean warming, hypoxia and hypercapnia, suggested by
      climate projections, may push an organism earlier to the limits of its thermal
      tolerance window. In a previous study on juveniles of green abalone (Haliotis
      fulgens), combined exposure to hypoxia and hypercapnia during heat stress induced
      a lowered critical thermal maximum (CTmax), indicated by constrained oxygen
      consumption, muscular spams and loss of attachment. Thus, the present study
      investigated the cell physiology in foot muscle of H. fulgens juveniles exposed
      to acute warming (18  degrees C to 32  degrees C at +3  degrees C day-1) under
      hypoxia (50% air saturation) and hypercapnia (~1000 MUatm PCO2), alone and in
      combination, to decipher the mechanisms leading to functional loss in this
      tissue. Under exposure to either hypoxia or hypercapnia, citrate synthase (CS)
      activity decreased with initial warming, in line with thermal compensation, but
      returned to control levels at 32  degrees C. The anaerobic enzymes lactate and
      tauropine dehydrogenase increased only under hypoxia at 32  degrees C. Under the
      combined treatment, CS overcame thermal compensation and remained stable overall,
      indicating active mitochondrial regulation under these conditions. Limited
      accumulation of anaerobic metabolites indicates unchanged mode of energy
      production. In all treatments, upregulation of Hsp70 mRNA was observed already at
      30  degrees C. However, lack of evidence for Hsp70 protein accumulation provides
      only limited support to thermal denaturation of proteins. We conclude that under
      combined hypoxia and hypercapnia, metabolic depression allowed the H. fulgens
      musculature to retain an aerobic mode of metabolism in response to warming but
      may have contributed to functional loss.

PMID- 30195086
TI  - The use of model constructs to design collaborative health information
      technologies: A case study to support child development.
AB  - OBJECTIVE: Health information technology could provide valuable support for inter
      professional collaboration to address complex health issues, but current HIT
      systems do not adequately support such collaboration. Existing theoretical
      research on supporting collaborative work can help inform the design of
      collaborative HIT systems. Using the example of supporting collaboration between
      child development service providers, we describe a deductive approach that
      leverages concepts from the literature and analyzes qualitative user-needs data
      to aid in collaborative system design. MATERIALS AND METHODS: We use the
      Collaboration Space Model to guide the deductive qualitative analysis of
      interviews focused on the use of information technology to support child
      development. We deductively analyzed 44 interviews from two separate research
      initiatives and included data from a wide range of stakeholder groups including
      parents and various service providers. We summarized the deductively coded
      interview excerpts using quantitative and qualitative methods. RESULTS: The
      deductive analysis method provided a rich set of design data, highlighting
      heterogeneity in work processes, barriers to adequate communication, and gaps in
      stakeholder knowledge in supporting child development work. DISCUSSION: Deductive
      qualitative analysis considering constructs from a literature-based model
      provided useful, actionable data to aid in design. Design implications underscore
      functions needed to adequately share data across many stakeholders. More work is
      needed to validate our design implications and to better understand the
      situations where specific system features would be most useful. CONCLUSIONS:
      Deductive analysis considering model constructs provides a useful approach to
      designing collaborative HIT systems, allowing designers to consider both
      empirical user data and existing knowledge from the literature. This method has
      the potential to improve designs for collaborative HIT systems.

PMID- 30195090
TI  - Diagnostic performance of multiplex PCR on pulmonary samples versus
      nasopharyngeal aspirates in community-acquired severe lower respiratory tract
      infections.
AB  - BACKGROUND: PCR-based techniques for the diagnosis of community- acquired severe
      lower respiratory tract infections are becoming the standard of care. However,
      their relative ability to identify either atypical bacteria or viruses that cause
      LRTI from clinical samples from various sources is yet to be determined.
      OBJECTIVES AND STUDY DESIGN: The aim of our study was to compare the diagnostic
      yield of nasopharyngeal aspirates with that of pulmonary samples for the
      etiological diagnosis of severe acute lower respiratory tract infections by
      multiplex PCR. Patients were adults with community-acquired pneumonia or acute
      exacerbation of chronic obstructive pulmonary disease. RESULTS: We obtained
      concordant results for 81 (79%) of the 103 pairs of samples. In 14 of the 22
      discordant results, more pathogens were evidenced in the lower respiratory tract
      samples. CONCLUSIONS: Pulmonary samples had a similar diagnostic sensitivity for
      virus detection by multiplex PCR as nasopharyngeal aspirates. In contrast, in our
      study, the diagnostic efficacy of pulmonary samples for Legionella pneumophila
      over simple aspirates was clearly superior.

PMID- 30195089
TI  - Association between decreasing estimated glomerular filtration rate and risk of
      cardiac conduction defects in patients with type 2 diabetes.
AB  - AIM: We aimed to assess the association between decreasing estimated glomerular
      filtration rate (eGFR) or abnormal albuminuria and the risk of certain cardiac
      conduction defects in patients with type 2 diabetes mellitus (T2DM). METHODS: We
      examined a hospital-based sample of 923 patients with T2DM discharged from our
      Division of Endocrinology over the years 2007-2014. Standard electrocardiograms
      (ECGs) were performed in all patients. eGFR was estimated by using the Chronic
      Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, whilst albuminuria
      was measured by an immuno-nephelometric method on morning spot urine samples.
      RESULTS: A total of 253 (27.4%) patients had some type of cardiac conduction
      defects on standard ECGs (defined as at least one heart block among first-degree
      atrioventricular block, second-degree block, third-degree block, left bundle
      branch block, right bundle branch block, left anterior hemi-block or left
      posterior hemi-block). Prevalence of patients with eGFRCKD-EPI < 30 mL/min/1.73
      m2, eGFRCKD-EPI 59-30 mL/min/1.73 m2 or abnormal albuminuria (i.e. urinary
      albumin-to-creatinine ratio >= 30 mg/g) were 7.0%, 29.4% and 41.3%, respectively.
      After adjustment for known cardiovascular risk factors, diabetes-related
      variables and potential confounders, there was a significant, graded association
      between decreasing eGFR values and risk of any cardiac conduction defects
      [adjusted-odds ratios of 2.05 (95% CI: 1.2-3.5), 2.85 (95% CI: 1.6-5.1) and 3.62
      (95% CI: 1.6-8.1) for eGFRCKD-EPI 89-60, eGFRCKD-EPI 59-30 and eGFRCKD-EPI < 30
      mL/min/1.73 m2, respectively]. Conversely, abnormal albuminuria was not
      independently associated with an increased risk of any conduction defects
      (adjusted-odds ratio: 1.09, 95% CI: 0.7-1.6). CONCLUSION: Decreasing eGFR is
      independently associated with an increased risk of cardiac conduction defects in
      hospitalized patients with T2DM.

PMID- 30195092
TI  - The State of Health Technology Assessment in the Ethiopian Health Sector:
      Learning from Recent Policy Initiatives.
AB  - Health technology assessment (HTA) has previously been implemented only in a
      fragmented manner in the Ethiopian health sector decision-making cycle, and the
      sector has been hampered by limited institutional capacity and skilled human
      resources to inform evidence-based decision making. The country is in the midst
      of widescale implementation of a community-based health insurance scheme and is
      preparing for the launch of a social health insurance scheme. The country
      continues to face a limited financial resource envelope, undergoing an
      epidemiological transition, and is facing a much greater burden of
      noncommunicable diseases, for which the essential health benefit package, defined
      12 years ago, may no longer be suitable. This has called for an in-depth review
      of the application of HTA in the context of the current health needs and
      institutional settings. To meet the increasing need for HTA, the Health Economics
      and Financing Analysis (HEFA) team was established within the Finance Resource
      Mobilization Department under the Ministry of Health. The HEFA team is tasked
      with spearheading the application of evidence-based health care decision making
      in Ethiopia by organizing available evidence, costing interventions, and defining
      effectiveness measures of the different health programs and then supporting
      policymakers at the national and regional levels. Improving and harmonizing the
      institutional approach to HTA, including staffing the HEFA team with the
      appropriate mix of expertise, and networking with relevant sector organizations
      will improve Ethiopia's ability to tackle the current health sector challenges as
      well as protect fledgling insurance schemes' progress toward universal health
      coverage.

PMID- 30195091
TI  - Standardizing protocols dealing with growth hormone receptor gene disruption in
      mice using the Cre-lox system.
AB  - OBJECTIVE: Mice and humans with reduced growth hormone (GH) action before birth
      are conferred positive health- and life-span advantages. However, little work has
      been performed to study the effect of conditional disruption of GH action in
      adult life. With this as our objective, we sought to elucidate a reproducible
      protocol that allows generation of adult mice with a global disruption of the GH
      receptor (Ghr) gene, using the tamoxifen (TAM)-inducible Cre-lox system, driven
      by the ROSA26 enhancer/promoter. Here we report the optimum conditions for the
      gene disruption. DESIGN: Six month old mice, homozygous for the ROSA26-Cre and
      the Ghr-floxed gene, were injected, once daily for five days with four distinct
      TAM doses (from 0.08 to 0.32 mg of TAM/g of body weight). To evaluate the most
      effective TAM dose that leads to global disruption of the GHR, mRNA expression of
      the Ghr and insulin growth factor-1 (Igf1) genes were assessed in liver, adipose
      tissue, kidney, and skeletal and cardiac muscles of experimental and control
      mice. Additionally, serum GH and IGF-1 levels were evaluated one month after TAM
      injections in both, TAM-treated and TAM-untreated control mice. RESULTS: A dose
      of 0.25 mg of TAM/g of body weight was sufficient to significantly reduce the Ghr
      and Igf1 expression levels in the liver, fat, kidney, and skeletal and cardiac
      muscle of six-month old mice that are homozygous for the Ghr floxed gene and Cre
      recombinase. The reduction of the Ghr mRNA levels of the TAM-treated mice was
      variable between tissues, with liver and adipose tissue showing the lowest and
      skeletal and cardiac muscle the highest levels of Ghr gene expression when
      compared to control mice. Moreover, liver tissue showed the 'best' Ghr gene
      disruption, resulting in decreased total circulating IGF-1 levels while GH levels
      were increased versus control mice. CONCLUSION: The results show that in mice at
      six months of age, a total TAM dose of at least 0.25 mg of TAM/g of body weight
      is needed for a global downregulation of Ghr gene expression with a regimen of
      100 MUL intraperitoneal (ip) TAM injections, once daily for five consecutive
      days. Furthermore, we found that even though this system does not achieve an
      equivalent disruption of the Ghr between tissues, the circulating IGF-1 is >95%
      decreased. This work helped to create adult mice with a global GHR knockdown.

PMID- 30195093
TI  - Drug Policy in Greece.
AB  - OBJECTIVES: To provide a detailed overview of the recent reforms in
      pharmaceutical pricing and reimbursement processes as well as in other important
      areas of the pharmaceutical policy in Greece. METHODS: Information was collected
      via a structured questionnaire. The study used publicly available resources, such
      as publications, relevant legislation, and statistical data, while health experts
      were also consulted. RESULTS: Recent pharmaceutical reforms included significant
      price cuts, increased co-payments and some provisions for vulnerable groups,
      rebates/clawbacks, mandatory electronic prescribing and prescription by
      international nonproprietary name, generics substitution, prescription limits and
      detailed auditing, centralized procurement, as well as changes in the pricing and
      reimbursement processes, with the introduction of positive and negative lists and
      an internal price referencing system. Price lists are compiled by the National
      Organization for Medicines and are issued by the Ministry of Health (MoH). An
      advisory pricing committee comprising representatives of stakeholder groups was
      abolished in early 2018. Nevertheless, under the new provisions, a health
      technology assessment body for the economic evaluation of reimbursed drugs is to
      be established for the first time in Greece. The committee is to be staffed by
      experts appointed by a ministerial decision of the MoH. The specific features of
      the process are yet to be determined. CONCLUSIONS: The pricing and reimbursement
      decision-making processes are centralized under the competence of the MoH.
      Despite the good intentions of the reformers, there are still some aspects of
      transparency, equity, and long-term sustainability that remain under question in
      Greece.

PMID- 30195094
TI  - Sympathetic neurotransmission in spleens from aging Brown-Norway rats subjected
      to reduced sympathetic tone.
AB  - Senescence of innate and adaptive responses and low-grade inflammation
      (inflammaging) hallmarks normal aging, which increases vulnerability to
      infectious diseases, autoimmunity and cancer. In normal aging, sympathetic
      dysregulation contributes to the dysregulation of innate and adaptive immunity
      and inflammaging. Sympathetic innervation of immune cells in secondary immune
      organs regulates immune responses. Previously in Fischer 344 (F344) rats, we
      reported an age-related increase in sympathetic tone and sympathetic dysfunction
      in beta-adrenergic receptor (AR) signaling of splenic lymphocytes that
      contributes to immune senescence, although the responsible mechanisms remains
      unexplored. In this study, we extend our previous findings using the much longer
      lived Brown-Norway (BN) rats, whose behavior and immune response profile differ
      strikingly from F344 rats. Here, we investigated whether increased sympathetic
      nerve activity (SNA) in the aging spleen contributes to age-related sympathetic
      neuropathy and altered neurotransmission in splenic lymphocytes in BN rats.
      Fifteen-month male BN rats received 0, 0.5 or 1.5 MUg/kg/day rilmenidine
      intraperitoneally for 90 days to lower sympathetic tone. Untreated young and age
      matched rats controlled for effects of age. We found that elevated SNA in the
      aging BN rat spleen does not contribute significantly to sympathetic neuropathy
      or the aging-induced impairment of canonical beta-AR signal transduction. Despite
      the rilmenidine-induced increase in beta-AR expression, splenocyte c-AMP
      production was comparable with age-matched controls, thus dampening nerve
      activity had no effect on receptor coupling to adenylate cyclase. Understanding
      how aging affects neuroimmune regulation in healthy aging rodent models may
      eventually lead to strategies that improve health in aging populations vulnerable
      to immunosenescence and low-grade systemic inflammation.

PMID- 30195096
TI  - Spatially-incoherent annular illumination microscopy for bright-field optical
      sectioning.
AB  - Numerous advanced microscopic imaging techniques have been proposed for optical
      sectioning, but they generally employ a complex and costly optical system. Here
      we report a microscopy termed spatially-incoherent annular illumination
      microscopy (SAIM). It allows for simple, effective, non-fluorescence, and bright
      field optical sectioning. The proposed technique is implemented by installing an
      annular array of light emitting diodes (LEDs) on a standard bright-field
      microscope for illumination. The LED array produces distinctive illumination,
      that is, each LED provides coherent, large-angle oblique illumination while all
      LEDs generate spatially-incoherent annular illumination. Such a distinctive
      illumination can improve both lateral resolution and axial resolution. The
      improvement of lateral resolution is due to the coherent and large-angle oblique
      illumination. The spatially-incoherent annular illumination can improve the axial
      resolution. It is because, for defocused structures, each LED results in a
      blurred image with a different lateral shift and all LEDs result in an incoherent
      stagger superposition of the defocused images. The superposition looks much more
      blurred, which improves the contrast of the in-focus image remarkably. We
      experimentally demonstrate that SAIM is able to provide bright-field optical
      sections with 600-nm axial resolution and 150-nm lateral half-pitch resolution by
      using a 525-nm wavelength LED array and an objective with 100X, numerical
      aperture (NA) 1.25.

PMID- 30195095
TI  - In situ atomic scale mechanisms of strain-induced twin boundary shear to high
      angle grain boundary in nanocrystalline Pt.
AB  - Twin boundary can both strengthen and soften nanocrystalline metals and has been
      an important path for improving the strength and ductility of nano materials.
      Here, using in-lab developed double-tilt tensile stage in the transmission
      electron microscope, the atomic scale twin boundary shearing process was in situ
      observed in a twin-structured nanocrystalline Pt. It was revealed that the twin
      boundary shear was resulted from partial dislocation emissions on the intersected
      {111} planes, which accommodate as large as 47% shear strain. It is uncovered
      that the partial dislocations nucleated and glided on the two intersecting {111}
      slip planes lead to a transition of the original <110> symmetric tilt ?3/(111)
      coherent twin boundary into a <110> symmetric tilt ?9/(114) high angle grain
      boundary. These results provide insight of twin boundary strengthening mechanisms
      for accommodating plasticity strains in nanocrystalline metals.

PMID- 30195097
TI  - Pre-traumatic vs post-traumatic OCD in PTSD patients: Are differences in
      comorbidity rates and functional health status related to childhood abuse?
AB  - OBJECTIVE: The goal of this study was to compare the clinical and functional
      status and the trauma-related characteristics of PTSD patients with comorbid OCD
      whose onset predated the index traumatic event (pre-traumatic OCD) with those of
      PTSD patient whose comorbid OCD only emerged after the exposure to the traumatic
      event (post-traumatic OCD). METHODS: Sixty-three individuals with PTSD and
      comorbid OCD were evaluated with the Structured Clinical Interview for DSM-IV
      AXIS I Disorders and completed the Posttraumatic Stress Disorder Checklist -
      Civilian Version, the Beck Depression Inventory, the Beck Anxiety Inventory, the
      Trauma History Questionnaire and the 36-Item Short-Form Health Survey. RESULTS: A
      history of childhood abuse was significantly more frequent among PTSD patients
      with pre-traumatic OCD (45.2%) than among their counterparts with post-traumatic
      OCD (16%). PTSD patients with pre-traumatic OCD had higher rates of psychiatric
      comorbidity in general and showed a lower functional health status in a physical
      domain (SF-36 Role Limitation due to Physical Health). In contrast, PTSD patients
      with post-traumatic OCD had a decreased functional health status in a
      psychological domain (SF-36 Emotional Well Being). The effect sizes were in the
      medium to large range. CONCLUSIONS: A history of child abuse may be an important,
      but often neglected, factor accounting for clinical, functional, and trauma
      related differences between pre-traumatic and posttraumatic OCD in PTSD patients.

PMID- 30195098
TI  - Somatic symptoms vary in major depressive disorder in China.
AB  - PURPOSE: This study aimed to investigate the clinical characteristics of somatic
      symptoms of patients in China who suffer from major depressive disorder (MDD).
      METHOD: 3273 patients who met the diagnostic criteria of Diagnostic and
      Statistical Manual of Mental Disorders (DSM-IV) MDD were recruited from 16
      general hospitals and 16 mental health centers in China. Physicians and patients
      completed complementary customized depression disorder symptomatology
      questionnaires assessing the clinical characteristics of patients with MDD.
      RESULT: 1. In this study we analyzed physician-recorded data. The major somatic
      symptoms in patients with MDD in China were insomnia (64.6%), pre-verbal physical
      complaints (46.9%), weight loss (38.5%), low appetite (37.6%), circulatory system
      complaints (31.3%), headache (31.3%), hyposexuality (31.0%), gastrointestinal
      symptom complaints (29.6%), and respiratory system complaints (29.6%). 2.
      Compared with MDD patients who sought medical help from mental health centers,
      MDD patients who sought medical help from general hospitals were more likely to
      suffer from urinary system complaints, headache, sensory system complaints, trunk
      pain, and nervous system complaints. A lower prevalence rate of insomnia and
      hyposexuality was also observed among MDD patients who visited general hospitals
      (p < .05). 3. Patients aged from 40 to 54 had the highest probability of pre
      verbal physical complaints, respiratory system complaints, trunk pain,
      hyposexuality, limb pain and other pain conditions, while patients over 55 years
      of age had the lowest prevalence respiratory system complaints, hyposexuality,
      and other pain conditions, and they also had the highest rate of low appetite and
      insomnia. 4. Female patients appeared to exhibit higher rates of pre-verbal
      physical complaints, low appetite, and insomnia than male patients, but had fewer
      urinary systems complaints than male patients (p < .05). CONCLUSION: The major
      somatic symptoms in patients with MDD in China are insomnia, pre-verbal physical
      complaints, weight loss, low appetite, circulatory system complaints, headache,
      hyposexuality, gastrointestinal system complaints, and respiratory system
      complaints. These symptoms vary by the type of medical setting to which patients
      present, and well as by age, and gender.

PMID- 30195099
TI  - Differentiating tic-related from non-tic-related impairment in children with
      persistent tic disorders.
AB  - Children with persistent (chronic) tic disorders (PTDs) experience impairment
      across multiple domains of functioning, but given high rates of other non-tic
      related conditions, it is often difficult to differentiate the extent to which
      such impairment is related to tics or to other problems. The current study used
      the Child Tourette's Syndrome Impairment Scale - Parent Report (CTIM-P) to
      examine parents' attributions of their child's impairment in home, school, and
      social domains in a sample of 58 children with PTD. Each domain was rated on the
      extent to which the parents perceived that impairment was related to tics versus
      non-tic-related concerns. In addition, the Yale Global Tic Severity Scale (YGTSS)
      was used to explore the relationship between tic-related impairment and tic
      severity. Results showed impairment in school and social activities was not
      differentially attributed to tics versus non-tic-related impairment, but
      impairment in home activities was attributed more to non-tic-related concerns
      than tics themselves. Moreover, tic severity was significantly correlated with
      tic-related impairment in home, school, and social activities, and when the
      dimensions of tic severity were explored, impairment correlated most strongly
      with motor tic complexity. Results suggest that differentiating tic-related from
      non-tic-related impairment may be clinically beneficial and could lead to
      treatments that more effectively target problems experienced by children with
      PTDs.

PMID- 30195100
TI  - Mental health and the jilted generation: Using age-period-cohort analysis to
      assess differential trends in young people's mental health following the Great
      Recession and austerity in England.
AB  - Those born in the United Kingdom post-1979 have been described as a 'jilted
      generation', materially disadvantaged by economic and social policy; however, it
      is unclear whether this resulted in their experiencing poorer mental health than
      previous cohorts. Following the 2008 recession, UK austerity reforms associated
      with worsening mental health also disproportionately impacted those of younger
      working-age. This study aimed to identify any historic cohort changes in
      population mental health, and whether austerity widened generational
      inequalities. Repeat cross-sectional data from the Health Survey for England
      (1991-2014) were used to calculate prevalence of psychopathology for those of
      younger and older working-age (16-30 and 31-64 years) and retirement-age (65+
      years), measured by General Health Questionnaire-12 (GHQ) score >= 4 (caseness).
      Descriptive age-period-cohort analysis was performed for 15-year birth cohorts,
      including the jilted generation (born 1976-90). Logistic regression tested
      differences in outcome between groups. Age-specific GHQ caseness between
      successive birth cohorts did not significantly change for men, and significantly
      improved between 2.8% (95% CI 0.1%-5.5%) and 4.4% (95% CI 2.2%-6.7%) for women.
      Secondary analysis adjusting for education partially explained this improvement.
      Following the recession, GHQ caseness worsened in men of younger and older
      working-age by 3.7% (95% CI 1.2%-6.2%) and 3.5% (95% CI 2.1%-5.0%) respectively
      before returning to baseline during austerity. All women experienced non
      significant increases post-recession, but trends diverged during austerity with
      caseness worsening by 2.3% (95% CI 1.0%-3.6%) for older working-age women versus
      3.7% (95% CI 1.3%-6.2%) for younger working-age women. Those of retirement-age
      experienced little change throughout. In summary, mental health has historically
      improved between successive cohorts, including for the jilted generation.
      However, the 2008 recession and subsequent austerity could be most impacting
      those of younger working-age, particularly women, to create a new cohort effect.
      Policymakers should consider the differential impact economic and social policy
      may have across society by age.

PMID- 30195101
TI  - Life cycle assessment of upgrading options of a preliminary wastewater treatment
      plant including food waste addition.
AB  - Life cycle assessment (LCA) is a beneficial tool to evaluate the performance of
      wastewater treatment plants (WWTPs) and to compare different upgrading options.
      The main objective of this study is to investigate the environmental impact of
      upgrading options of a preliminary WWTP in Istanbul, Turkey. The preliminary
      plant currently consists of mechanical treatment units and various upgrading
      options including primary treatment and high-rate activated sludge system (HRAS)
      process as well as the addition of food waste to wastewater were compared.
      Results showed that the baseline scenario (S0) had worse performance than all
      future scenarios (S1-3) except for climate change. The scenario of adding food
      waste to wastewater (S3) has the best performance in climate change, terrestrial
      acidification, terrestrial ecotoxicity and fossil depletion. Increased addition
      of food waste was also tested in the sensitivity analysis, and major improvements
      were obtained especially in climate change and terrestrial ecotoxicity.

PMID- 30195102
TI  - Dimensional changes of the carpal tunnel and median nerve during manual
      mobilization of the carpal bones - Anatomical study.
AB  - STUDY DESIGN: Cross-sectional study. BACKGROUND: The carpal tunnel is a
      clinically important fibro-osseous conduit for the median nerve and associated
      tendons. It is mechanically dynamic and therapeutic manual techniques that appear
      to move and change tunnel shape is part of clinical practice. OBJECTIVES: To
      measure changes in dimensions of the carpal tunnel and median nerve with manual
      mobilization of the carpal bones in cadavers. METHODS: A total of 20
      cryopreserved upper extremities from cadaveric specimens were used in the study.
      The wrist was cut using an anatomical saw at the level of the pisiform.
      Measurements of the cross-sectional area (CSA), anteroposterior diameter (APD),
      transverse diameter (TD), perimeter, flattening ratio and circularity of the
      carpal tunnel and of the median nerve, were taken, both in the anatomical
      position of the wrist and during the mobilization technique of the carpal bones.
      RESULTS: During the mobilization technique, the tunnel CSA (p < 0.011), APD (p <
      0.001) and circularity (p < 0.001) significantly increased, while TD (p < 0.001),
      perimeter (p < 0.004) and flattening ratio (p < 0.001), decreased. The median
      nerve showed similar behavioral tendencies to the tunnel but only the CSA (p <
      0.005), APD (p < 0.005) and flattening ratio (p < 0.004) of the nerve showed
      significant differences. CONCLUSION: Application of external manually applied
      compressive force across the wrist can increase the CSA of the carpal tunnel and
      the median nerve in cadavers. These results are consistent with other studies in
      which similar results were found non-invasively using ultrasound.

PMID- 30195103
TI  - Motherhood inmigrant women in Chile: A qualitative study.
AB  - BACKGROUND: The adverse impact of poverty and migration in pregnant women is
      expressed in diverse results in reproductive, mental and child health, all of
      which are related to lack of documentation to reside in the country, absence of
      health insurance and no economic resources to pay private services, or either not
      understanding the administrative procedures. OBJECTIVE: To understand the
      experience of immigrant women in the process of motherhood and rearing infants
      under 6 months, in the context of social vulnerability in an urban area of
      Santiago de Chile. DESIGN: Qualitative research design, with descriptive analysis
      data and interpretation gradually given to explicity the findings relevant the
      study with women from a healthcare center in the urban region of Chile.
      PARTICIPANTS: The sample was deliberate by criterion, the participants were
      thirteen immigrant women between the ages of 18 and 40 years old. Guided open
      ended interview were performed after providing informed consent. In the analysis
      of information, the following criteria was applied: credibility, authenticity,
      possibility of confirmation, dependence and transferability. FINDINGS: From
      immigrant's women discourses, difficulties to access the health system could be
      observed, due to institutional and structural barriers that represented a
      limitation for social and cultural integration. In addition, feelings of
      mistrust, tension and insecurity about reaching for healthcare and social support
      for them and their family, produces a series of problems for the women and their
      children. CONCLUSION: Immigrant women face cultural and institutional barriers,
      as well as social and personal adversities that conditions a complex process of
      social vulnerability to take responsibility for a safe motherhood and rearing.
      Living the phases of the migration process and an unwanted pregnancy - in most
      cases - made the women face the challenge of rearing in another country, in
      economic vulnerability, emotional instability with their partners and with social
      and cultural barriers with healthcare teams. IMPLICATIONS FOR PRACTICE: It is
      necessary to mention the role of the midwifery and nursing from the point of view
      of assistance, due to their responsibility in accompanying the child-rearing
      period for both native and immigrant women for years. It is worth mentioning the
      theory of culturation, referring to the need for knowledge of the cultural and
      social structure of an individual, family and community, which provides an
      integrated, interdisciplinary and cross-cultural approach to care in contexts of
      vulnerability conditioned by migration.

PMID- 30195104
TI  - Radiochromic film containing poly(hexa-2,4-diynylene adipate) as a radiation
      dosimeter.
AB  - A radiation-sensitive polymer poly(hexa-2,4-diynylene adipate) (PHDA) was
      synthesized and incorporated into polyvinyl butyral films for radiation dose
      measurements in the 0.5 - 60 kGy range. PHDA undergoes crosslinking
      polymerization upon exposure to gamma-rays, which changes its color from very
      pale yellow to deep orange-yellow. The color change is directly related to the
      absorbed dose. The absorption spectrum of the irradiated films features one
      absorption band around 500 nm with a shoulder around 465 nm. With increasing
      absorbed dose, the two bands grow in intensity and move towards higher
      wavelengths. The dosimeter is nearly insensitive to variations of the humidity in
      the range of 0-54% and temperature in the range of 30-45  degrees C during
      irradiation. The color intensifies after irradiation, both in the dark and in the
      light at room temperature, which reflects the continuing crosslinking
      polymerization. However, at - 4  degrees C, the color intensity does not change
      with time.

PMID- 30195105
TI  - Long-term plasticity of hippocampal interneurons during in vivo memory processes.
AB  - Formation of a cell assembly, a group of cortical neurons that function co
      operatively to sustain an active memory trace, arises from changes in the
      connections between neurons. Establishment of memory traces is thought to rely on
      long-term plasticity in excitatory glutamatergic synapses interconnecting
      principal cells. In addition, recent studies in the hippocampus in vivo indicate
      that reconfiguration of GABAergic inhibitory interneuron activity also occurs
      during long-term memory encoding. Recent experiments in anesthetized, as well as
      in freely moving animals, demonstrate that learning-related hippocampal
      activities are associated with persistent changes in GABAergic interneuron firing
      rates and alterations in protein expression levels regulating GABA release.

PMID- 30195106
TI  - A new method for simultaneous quantification of fosphenytoin, phenytoin and its
      primary metabolite 5-(4-hydroxyphenyl)-5-phenylhydantoin in whole blood by ultra
      performance liquid chromatography-tandem mass spectrometry.
AB  - A method for simultaneous quantification of fosphenytoin (F-PHT), phenytoin (PHT)
      and its main metabolite 5-(4-hydroxyphenyl)-5-phenylhydantoin (HPPH) in whole
      blood was developed and validated using ultra-performance liquid chromatography
      tandem mass spectrometry. Whole blood samples were pretreated by liquid-liquid
      extraction with acetonitrile and methanol. Chromatographic separation was
      performed using a CORTECSTM UPLC(r) C18 (2.1 * 50 mm i.d., particle size 1.6 MUm)
      analytical column, and water containing 10 mM ammonium formate and acetonitrile
      as the mobile phase. Quantification of the analytes was carried out using mass
      chromatography with each product ion referenced against phenytoin-d10 as an
      internal standard. Calibration curves exhibited good linear relationships in a
      range from 0.005 to 50 MUg/ml with correlation coefficients exceeding 0.995. The
      limits of detection were estimated to be 0.002-0.01 MUg/ml. The accuracies and
      precisions were 96.2-104.3% and 0.7-10.7%, respectively. The recovery
      efficiencies were in the range of 42.4-59.2%. Matrix effects were observed for
      PHT and HPPH, with signal suppression ranging from -6.6 to -32.2%. Matrix effect
      for F-PHT (-5.0 to 8.9%) was less than those for PHT and HPPH. All analytes were
      stable under different storage conditions. This method was successfully applied
      for the quantification of F-PHT, PHT and HPPH in rat whole blood samples taken
      after bolus intravenous administration of F-PHT.

PMID- 30195107
TI  - Impact of domestication on the evolution of rhizomicrobiome of rice in response
      to the presence of Magnaporthe oryzae.
AB  - The rhizomicrobiome plays a key role in suppressing soil-borne plant diseases. It
      remains unclear if crop domestication has altered the rhizomicrobiome and reduced
      the resistance of domesticated crops to pathogens. To investigate this question,
      the pathogenic fungus Magnaporthe oryzae was administered to the rhizosphere of
      plants of cultivated and wild rice to compare the impact of the fungal pathogen
      on their rhizomicrobiome. The analysis of the results indicated that the presence
      of M. oryzae affected the community structure and diversity of the
      rhizomicrobiome of both cultivated and wild rice species. Bacterial and fungal
      alpha- and beta-diversity of the rhizosphere of cultivated rice were altered more
      significantly than in wild rice. Furthermore, the abundance of the introduced
      pathogen was significantly lower in the rhizosphere of wild rice, while the
      relative abundance of putatively beneficial bacterial and fungal taxa was higher,
      relative to cultivated rice. These results suggest that the rhizomicrobiome of
      cultivated rice was more sensitive to the introduction of the fungal pathogen and
      more easily disturbed than the rhizosphere community of its wild relative.
      Additionally, a correlation analysis of microbiome and root transcriptome data,
      obtained under pathogenic and non-pathogenic conditions, indicated that fungal
      members of the Glomeromycota are important for promoting phenylpropanoid and
      lignin syntheses in wild rice, which plays a role in resisting M. oryzae
      infection. The identified differences between the responses of the
      rhizomicrobiomes of cultivated and wild rice to M. oryzae may provide information
      that can be used in developing novel strategies to control soil-borne pathogens,
      which include reconstructing the rhizomicrobiome of domesticated crops to be
      similar to their wild relatives.

PMID- 30195108
TI  - Baicalin exerts neuroprotective effects via inhibiting activation of GSK3beta/NF
      kappaB/NLRP3 signal pathway in a rat model of depression.
AB  - Chronic stress can provoke depressive-like behaviors through activation of
      inflammation and apoptosis, leading to a reduction of neurons. Antidepressant
      therapy may contribute to inhibiting inflammation responses and have
      neuroprotective effects. Baicalin (BA) has an antidepressant effect in the
      chronic unpredictable mild stress (CUMS) animal model and exerts anti
      inflammation, anti-apoptosis, as well as neuroprotective effects in many central
      nervous system (CNS)-related diseases. But the effects of BA on neuroprotection,
      apoptosis, and neuroinflammation and the potential mechanisms in depression are
      unclear. Here, we focused on examining the therapeutic effects of BA in CUMS
      induced depression rats and investigating the molecular mechanisms. Results
      showed that administration of BA improved depressive-like behaviors and
      significantly increased the levels of doublecortin (DCX), Neuron-specific enolase
      (NSE), and Brain-derived neurotrophic factor (BDNF) in hippocampus. Furthermore,
      administration of BA increased the cell survival by reducing the level of
      malondialdehyde (MDA) and increasing the level of superoxide dismutase (SOD).
      Finally, administration of BA significantly decreased CUMS-induced apoptosis and
      inflammatory cytokines (caspase-1 and IL-1beta) in hippocampus. These responses
      were mediated by Glycogen synthase kinase-3 (GSK3) beta/Nuclear factor-kappaB (NF
      kappaB)/Nucleotide-binding domain, leucine-rich repeat, pyrin domain containing
      protein 3 (NLRP3) signal pathway. Taken together, these results indicate that BA
      could promote neuronal maturation and rescue neurons from apoptosis via
      inhibiting activation of GSK3beta/NF-kappaB/NLRP3 signal pathway that is known to
      be associated with inflammation, thus exerting neuroprotective effects and
      preventing CUMS-induced depressive-like behaviors.

PMID- 30195109
TI  - A novel Gallic acid derivative attenuates BLM-induced pulmonary fibrosis in mice.
AB  - Idiopathic Pulmonary fibrosis is a disease with high morbidity and mortality.
      Therefore, the development of new drugs is imperative. Gallic acid derivative is
      a derivative of Gallic acid that can be extracted from Chinese herbal medicine.
      In previous experiments, we found that Gallic acid derivative played dual roles
      in inflammatory and antioxidant activities. Meanwhile, Gallic acid derivative
      could inhibit the proliferation of lung fibroblast. In the present study, we
      investigated the function of Gallic acid derivative in inhibiting lung fibrosis.
      5 mg/kg of bleomycin was administered to mice by a single intratracheal
      instillation. Three dosages of Gallic acid derivative (75 mg/kg, 150 mg/kg, 300
      mg/kg) and Pirfenidone (80 mg/kg) were given to mice for 21 day. Gallic acid
      derivative treatment significantly reduced lung histological changes and
      decreased inflammatory cell infiltration. The content of collagen decreased with
      the decrease of hydroxyproline level. Analogously, the expression of alpha smooth
      muscle actin was reduced. Gallic acid derivative enhanced the antioxidant status,
      but reduced the expression of interleukin 6, NADPH oxidase-4. Our study proved
      that Gallic acid derivative reduced inflammation activation to some extent and
      could exert its effects through transforming growth factor beta1/Smad2 signaling
      pathway and balancing NOX4/Nrf2.

PMID- 30195111
TI  - Facile synthesis of hierarchical lychee-like Zn3V3O8@C/rGO nanospheres as high
      performance anodes for lithium ion batteries.
AB  - In the present work, the hierarchical Zn3V3O8@C/rGO composite with a unique
      lychee-like architecture was fabricated by a simple one-pot ethanol thermal
      reduction strategy. When used as an anode material, it exhibited outstanding
      electrochemical performance for lithium-ion batteries (LIBs). For instance, the
      Zn3V3O8@C/rGO composite delivers high reversible capacities (1012 mAh g-1 at 0.1
      A g-1 after 200 cycles) and high rate stability (448 mAh g-1 at 4 A g-1 after
      1000 cycles). This outstanding performance can be attributed to the synergistic
      effect of the diverse structural virtues, effective interface and dual-spatially
      hybrid carbon network. Significantly, this one-pot simple strategy can be
      extended to fabricating highly stable and high rate performance of vanadates or
      other anode materials for LIBs.

PMID- 30195110
TI  - Innate immune activation and depressive and anxious symptoms across the
      peripartum: An exploratory study.
AB  - BACKGROUND: There are complex associations between immune function and mental
      illness, yet studies in the perinatal period focus primarily on individual
      inflammatory markers and depressive symptoms only, cross-sectionally. We sought
      to examine associations between both depressive and anxious symptoms and immune
      activation longitudinally across the peripartum. METHODS: We measured mood (Beck
      Depression Inventory, BDI-1 A) and anxiety (State-Trait Anxiety Inventory, STATE)
      and levels of 23 cytokines at 5 points in pregnancy and postpartum in 51 women.
      Within subject cytokine trajectories over time by depressive and anxious symptom
      grouping were assessed using linear mixed effects models with random intercept
      and slope. We also undertook an exploratory cluster analysis based on third
      trimester cytokine values. RESULTS: Based on categorical BDI scores, IL-6 (p < 
      0.001), IL-15 (p =  0.047), GCSF (p = 0.003), and CCL3 (p < .001) were
      significantly different across time, with IL-6 (p <  0.001), IL-15 (p =  0.003),
      and CCL3 (p <  0.001) higher at the third trimester visit in more depressed
      subjects. Based on categorical STATE scores, GM-CSF significantly decreased
      across pregnancy for the less anxious group (p = 0.016), but not for the more
      anxious, and CCL3 (p = 0.017), CXCL8 (p = 0.011), and IL-6 (p < 0.001) were
      higher at the third trimester visit for more anxious subjects. In exploratory
      cluster analysis based on cytokine level, there were no differences in mood or
      anxiety scores, but significant differences by race/ethnicity and
      overweight/obesity status. Women with higher pro-inflammatory cytokine values are
      more likely to be Hispanics (69.2% vs. 21.4%, p =  0.015), but less likely to be
      African American (23.1% vs. 60.7%, p = 0.015) or overweight/obese (25% vs. 69.2%,
      p =  0.016) compared to women with lower pro-inflammatory cytokine values.
      CONCLUSION: We identified a pro-inflammatory burst at the third trimester,
      indicative of innate immune activation, in women with higher levels of both
      depressive and anxious symptoms, as well as differences in pro-inflammatory
      changes across time. We also found significant differences in cytokine levels by
      race, ethnicity, and overweight/obesity status. These results point the way
      toward future longitudinal work that considers race/ethnicity, timing, and weight
      status, and evaluates perinatal mood and anxiety disorders in the context of
      changing immune functioning across the peripartum.

PMID- 30195112
TI  - Fabrication of visible-light-driven silver iodide modified iodine-deficient
      bismuth oxyiodides Z-scheme heterojunctions with enhanced photocatalytic activity
      for Escherichia coli inactivation and tetracycline degradation.
AB  - At present, various organic pollutants and pathogenic microorganisms presented in
      wastewater have severely threatened aquatic ecosystem and human health.
      Meanwhile, semiconductor photocatalysis technology for water purification has
      attracted increasingly significant attention. Herein, we successfully constructed
      a series of novel visible-light-driven (VLD) Bi4O5I2/AgI hybrid photocatalysts
      with different AgI amounts. Compared with pristine AgI and Bi4O5I2, Bi4O5I2/AgI
      with the optimal AgI contents exhibited remarkably enhanced photocatalytic
      performance in probe experiment for Escherichia coli (E. coli) disinfection and
      tetracycline (TC) degradation. The efficiency for TC degradation and E. coli
      inactivation reached 82% and 100% in 30 min, respectively. The enhanced electron
      hole separation efficiency was responsible for improved photocatalytic activity.
      In addition, the destruction process of the chemical structure of TC molecules
      was further investigated by three-dimensional excitation-emission matrix
      fluorescence spectra (3D EEMs). The activity and crystal phase of the catalysts
      did not change significantly after four cycles, demonstrating their excellent
      recyclability and stability of catalysts. The Ag+ ion leaking experiments,
      radical trapping experiments and ESR tests demonstrated that OH, O2- and h+ were
      the main active species in photocatalytic disinfection processes. Furthermore,
      the photocatalytic mechanism of Bi4O5I2/AgI nanomaterials was discussed in detail
      in conjunction with the energy band structure, and a reasonable Z-scheme
      interfacial charge transfer mechanism was proposed. This work is expected to
      provide an efficient water disinfection method.

PMID- 30195113
TI  - Multilayer ultrathin Ag-delta-Bi2O3 with ultrafast charge transformation for
      enhanced photocatalytic nitrogen fixation.
AB  - Photocatalytic nitrogen fixation provides an attractive approach to produce
      reactive nitrogen compounds at benign conditions. Herein, Ag decorated delta
      Bi2O3 photocatalyst, which has the features of multilayer ultrathin structure,
      suitable absorption edge and many exposed surface sites, is prepared by a
      hydrothermal and photoreduction process. Under visible light illustration, the
      obtained Ag-delta-Bi2O3 photocatalyst exhibits efficient photocatalytic activity
      for NH4+ generation at room temperature and atmospheric pressure in aqueous
      solution. The multilayer ultrathin sheets in the structure of Ag-delta-Bi2O3
      favors the effective separation of photogenerated electron-hole pairs and fast
      interfacial charge transfer. Due to the Ag surface plasmonic resonance, obvious
      trap is formed in the ultrathin Ag-delta-Bi2O3 sheets, which not only inhibites
      the recombination of electron hole pairs but also produces light-induced oxygen
      vacancies under irradiation. Those factors significantly improve the
      photocatalytic ability of as-prepared Ag-delta-Bi2O3. The results provide
      insights into rational design of enhanced active photocatlysts with Ag surface
      plasmonic resonance and ultrafast charge carrier transfer for photocatalytic
      nitrogen fixation.

PMID- 30195114
TI  - Enhanced selectivity and performance of heterogeneous cation exchange membranes
      through addition of sulfonated and protonated Montmorillonite.
AB  - Novel heterogeneous cation exchange membranes, based on poly (ether sulfone) and
      cation exchange resin, were prepared with the addition of protonated and
      sulfonated Montmorillonite (MMT) nanoparticles. Detailed investigations were then
      carried out studying the morphology, physical properties and the performance of
      membranes. It is observed that addition of MMT, leads to a substantially better
      distribution of ion exchange resin in the polymer matrix. This leads, at low
      loadings of MMT (0.5 wt.%), to membranes that are more hydrated, more hydrophilic
      and with higher ion exchange capacities. Especially at these low MMT loadings,
      substantially better membrane performance is observed, with higher
      permselectivities, lower areal resistances and increased ion transport during
      electrodialysis. A very surprising effect is that the addition of MMT has a
      strong effect on the selectivity of the membranes, especially towards Mg2+. A
      high affinity of the nanoclay towards Mg2+, selectively slows down Mg2+ transport
      through the nanoclay containing membrane. At low MMT loadings this leads to a
      much higher areal resistance for Mg2+, while for Na+ and Ca2+ the areal
      resistance is decreased. This leads to resistance based selectivities of 5.5 for
      Na+/Mg2+ and 4.5 for Ca2+/Mg2+. Under more challenging electrodialysis operation
      selectivities become lower, but persist at 2.6 for Na+/Mg2+ and 2.04 for
      Ca2+/Mg2+, outperforming commercial Ralex membranes. Overall, the protonated clay
      leads to slightly better membrane performances and selectivities than the
      sulfonated clay, likely due to a better compatibility with PES.

PMID- 30195115
TI  - Investigating structure-dependent diffusion in hydrogels using spatially resolved
      NMR spectroscopy.
AB  - HYPOTHESIS: Incorporation of the drug-loaded surfactant micelles into polymer
      hydrogels is a common method used to achieve controlled drug delivery. The
      characterization of the diffusion processes in drug delivery systems is critical
      in order to tune the drug loading and release. EXPERIMENTS: We present a simple
      and efficient NMR protocol to investigate the transport of the surfactant
      molecules in hydrogels on micro- and macroscale under non-equilibrium conditions.
      Our experimental protocol is based on a combination of 1H 1D NMR chemical shift
      imaging and slice-selective diffusion experiments, which enables determination of
      the mutual and self-diffusion coefficients of the surfactant in the non
      equilibrium hydrogel-based system within the same short time frame. FINDINGS: Our
      results show that the self-diffusion coefficient of the positively charged
      surfactant in the hydrogel (Dsgel) decreases with the increasing surfactant
      concentration until it reaches a plateau value of 6.6+/-0.5*10-11m2s-1. The
      surfactant self-diffusion in the solution (Dssln) remains constant over the
      experiment with an average value of 6.7+/-0.3*10-11m2s-1. The surfactant mutual
      diffusion coefficient obtained from 1D chemical shift imaging in this hydrogel
      system (Dm) is 7.7+/-0.5*10-11m2s-1. Correlation of the localized Ds to the 1D
      chemical shift images gives insight into the structure-dependent diffusional
      behavior of surfactant molecules in the hydrogel. This NMR protocol will be of
      great value in studies of concentration dependent structures on the interfaces
      between two immiscible liquids.

PMID- 30195116
TI  - Comparative study of the wear of the pair human teeth/Vita Enamic(r) vs commonly
      used dental ceramics through chewing simulation.
AB  - Ceramic based prosthetic materials have been used in dental restorations due to
      their excellent aesthetic and biocompatibility. However, due to concerns related
      to their mechanical properties and abrasive action against natural teeth, a
      proper selection of these materials is crucial to preserve the occlusal
      interactions and prevent abnormal dental wear. The aim of this work is to compare
      the wear performance of Vita Enamic(r), a polymer infiltrated ceramic (PIC), with
      that of other three commercial ceramic based dental materials - Zirconia, Leucite
      and Zirconia Veneered - when tested against natural teeth. The crystalline
      structure, wettability, topography and hardness of the prosthetic materials were
      characterized before wear testing. Chewing simulator experiments (360,000 cycles,
      load 49 N) against dental human cusps were carried out using artificial saliva as
      lubricant. The wear of both teeth and prosthetic materials was quantified and the
      involved wear mechanisms were analyzed by scanning electron microscopy. The
      results showed that Zirconia presented the most suitable tribological behavior,
      since it led to the lowest wear on both occlusal surfaces. The prosthetic
      material presenting the highest wear was Vita Enamic(r). Regarding the cusps'
      wear, the highest values were found for both Leucite and Zirconia Veneered.
      Polishing wear was the main wear mechanism in Zirconia system (prosthetic
      material and opposing enamel), while in the remaining ones was fragile fracture
      associated with abrasive wear. No direct relation could be established between
      wettability, initial roughness and hardness of the prosthetic materials and the
      wear of the tribological systems. Contrarily, microstructure and toughness
      revealed to be critical parameters.

PMID- 30195117
TI  - Carbon dots intensified poly (ethylene glycol)/chitosan/sodium glycerophosphate
      hydrogel as artificial synovium tissue with slow-release lubricant.
AB  - The ultra-high molecular weight polyethylene (UHMWPE) and metal artificial joint
      pair is limited by wear debris and short service life. Here we report the
      development of a hydrogel which exhibits lubricant release to intensify the
      lubrication effect of artificial joints.This study adopted an injectable method
      to prepare carbon dots/poly (ethylene glycol)/chitosan/sodium glycerophosphate
      (CDs/PEG/CS/GP) composite hydrogel, and the carbon dots were used to intensify
      the rheological and mechanical properties. In addition, the composite hydrogel
      had slow-release properties, and the release solution contained CDs, PEG and GP
      has excellent lubrication effect. At last, the MTT assay, LIVE/DEAD staining, H&E
      staining results and safety evaluation in BALC/c mice proved that the hydrogels
      had good biocompatibilility and were safety for application in vivo.

PMID- 30195119
TI  - Development of novel portable and reusable fiber optical chemiluminescent
      biosensor and its application for sensitive detection of microcystin-LR.
AB  - A novel portable fiber optical chemiluminescent biosensor (FOCB) system was
      successfully constructed using fiber optic bio-probe as biorecognition element as
      well as transducer and a Si-based photodiode detector (PD-3000). The compact
      design of FOCB with free magnetic beads and photomultiplier allows it to be
      portable and suitable for on-site and automatic detection of targets, as well as
      to be cost-effective and small sample volume (only 40.0 uL). The sensitivity of 5
      fW could be obtained for the FOCB due to the high performance of PD-3000 and no
      background light signal. Next, the FOCB was applied for the CL-based detection of
      microcystin-LR (MC-LR) in water using hapten-carrier protein conjugates modified
      fiber optic bio-probe as biorecognition element. Based on indirect competitive
      sandwich-like CL immunoassay principle, the highly sensitive detection of MC-LR
      was achieved using FOCB system. Under optimal conditions, the limit of detection
      for MC-LR is 0.03 ug/L, which is comparable with that of most reported MC-LR
      immunoassay methods. The robustness of the hapten-carrier protein-modified
      biosensor surface allowed multiple MC-LR immunoassays without any significant
      loss of performance, which ensured accurate and cost-effective detection results.
      The proposed strategy demonstrated good recovery, precision, and accuracy through
      the evaluation of the spiked water samples. The FOCB system can be readily
      extended toward the on-site real-time sensitive detection of other targets in the
      field of environment, food, and medical diagnosis.

PMID- 30195118
TI  - Self-powered photoelectrochemical aptasensor based on phosphorus doped porous
      ultrathin g-C3N4 nanosheets enhanced by surface plasmon resonance effect.
AB  - This work reports a facile and sensitive self-powered cathodic
      photoelectrochemical (PEC) aptasensor for the detection of oxytetracycline (OTC)
      based on Au nanoparticles-decorated phosphorus-doped porous ultrathin g-C3N4
      nanosheets (Au/PCN-S). The prepared PCN-S possesses large specific surface area
      with abundant in-plane pores on its surface, ideal biocompatibility, and
      excellent visible light response. The in situ photo-reduced Au nanoparticles
      further enhanced the PEC performance owing to its unique surface plasmon
      resonance (SPR) effect. Under visible light irradiation, the photocurrent of
      Au/PCN-S composites was significantly enhanced, which was about 22 times higher
      than that of pure g-C3N4. In the self-powered PEC biosensing of OTC, the device
      exhibited high sensitivity toward the presence of dissolved oxygen in the
      electrolyte and presented a wide detection range from 0.5 to 200 nM and a
      detection limit of 0.34 nM, as well as certain selectivity, reproducibility and
      stability. The proposed Au/PCN-S nanocomposites would be considered as a
      promising visible light-responsive photoactive material for fabrication of PEC
      biosensors with high performance.

PMID- 30195121
TI  - Using metabolome data for mathematical modeling of plant metabolic systems.
AB  - Plant metabolism is characterized by a wide diversity of metabolites, with
      systems far more complicated than those of microorganisms. Mathematical modeling
      is useful for understanding dynamic behaviors of plant metabolic systems for
      metabolic engineering. Time-series metabolome data has great potential for
      estimating kinetic model parameters to construct a genome-wide metabolic network
      model. However, data obtained by current metabolomics techniques does not meet
      the requirement for constructing accurate models. In this article, we highlight
      novel strategies and algorithms to handle the underlying difficulties and
      construct dynamic in vivo models for large-scale plant metabolic systems. The
      coarse but efficient modeling enables the prediction of unknown mechanisms
      regulating plant metabolism.

PMID- 30195120
TI  - A force sensor that converts fluorescence signal into force measurement utilizing
      short looped DNA.
AB  - A force sensor concept is presented where fluorescence signal is converted into
      force information via single-molecule Forster resonance energy transfer (smFRET).
      The basic design of the sensor is a ~100 base pair (bp) long double stranded DNA
      (dsDNA) that is restricted to a looped conformation by a nucleic acid secondary
      structure (NAS) that bridges its ends. The looped dsDNA generates a tension
      across the NAS and unfolds it when the tension is high enough. The FRET
      efficiency between donor and acceptor (D&A) fluorophores placed across the NAS
      reports on its folding state. Three dsDNA constructs with different lengths were
      bridged by a DNA hairpin and KCl was titrated to change the applied force. After
      these proof-of-principle measurements, one of the dsDNA constructs was used to
      maintain the G-quadruplex (GQ) construct formed by thrombin binding aptamer (TBA)
      under tension while it interacted with a destabilizing protein and stabilizing
      small molecule. The force required to unfold TBA-GQ was independently
      investigated with high-resolution optical tweezers (OT) measurements that
      established the relevant force to be a few pN, which is consistent with the force
      generated by the looped dsDNA. The proposed method is particularly promising as
      it enables studying NAS, protein, and small molecule interactions using a highly
      parallel FRET-based assay while the NAS is kept under an approximately constant
      force.

PMID- 30195122
TI  - Assessment of neuroplasticity in late-life depression with transcranial magnetic
      stimulation.
AB  - BACKGROUND: Studies using Transcranial Magnetic Stimulation (TMS), a non-invasive
      method of brain stimulation, have implicated impaired neuroplasticity in the
      pathophysiology of depression in younger adults. The role of neuroplasticity in
      late-life depression (LLD) has not yet been explored using TMS. OBJECTIVE: This
      study aimed at evaluating motor cortical neuroplasticity using paired associative
      stimulation (PAS). Single-pulse TMS was used to induce motor-evoked potentials
      (MEP) in the contralateral hand muscle before and after PAS. The potentiation of
      MEP amplitudes after PAS was used as an indirect index of associative plasticity
      and long-term potentiation (LTP) (i.e. PAS-LTP). RESULTS: 48 older adults with
      depression and 34 age-matched healthy controls (HC) were compared. PAS- LTP was
      successfully induced in 68.8% of older adults with depression and 47.1% of HC. At
      the group level, older adults with depression failed to show statistically
      significant induction of neuroplasticity, which was observed in HC. However, no
      significant differences were observed between the two groups for PAS-LTP.
      CONCLUSION: Our results suggest that associative plasticity does not differ
      substantially between older adults with depression and age-matched HC. Continued
      research is needed to more comprehensively understand the role of neuroplasticity
      in the pathophysiology of LLD.

PMID- 30195123
TI  - Congenital myopathy with fiber-type disproportion accompanied by dilated
      cardiomyopathy in a patient with a novel p.G48A ACTA1 mutation.

PMID- 30195124
TI  - Tai Chi exercise is more effective than brisk walking in reducing cardiovascular
      disease risk factors among adults with hypertension: A randomised controlled
      trial.
AB  - BACKGROUND: Physical inactivity is a major modifiable lifestyle risk factor
      associated with cardiovascular disease. Tai Chi is a safe and popular form of
      physical activity among older adults, yet direct comparisons are lacking between
      Tai Chi and brisk walking in their ability to reduce cardiovascular disease risk
      factors and improve psychosocial well-being. METHODS: 246 adults (mean age = 64.4
      +/- 9.8 years, age range = 30-91 years, 45.5% men) with hypertension and at least
      two but not more than three modifiable cardiovascular disease risk factors
      (diabetes, dyslipidaemia, overweight, physical inactivity and smoking) were
      randomly assigned to either Tai Chi (n = 82), brisk walking (n = 82) or control
      (n = 82) groups. The Tai Chi and brisk walking groups engaged in moderate
      intensity physical activity 150 min/week for 3 months; daily home-based practice
      was encouraged for another 6 months. The primary outcome was blood pressure.
      Secondary outcomes were fasting blood sugar, glycated haemoglobin, total
      cholesterol, triglycerides, high- and low-density lipoprotein, body mass index,
      waist circumference, aerobic endurance, perceived stress, quality of life and
      exercise self-efficacy. Data were collected at baseline, post-intervention at 3
      months and follow-up assessments at 6 and 9 months. Generalised estimating
      equation models were used to compare the changes in outcomes over time between
      groups. RESULTS: At baseline, the participants had an average blood pressure =
      141/81 and average body mass index = 26; 58% were diabetics, 61% presented with
      dyslipidemia and 11% were smokers. No significant difference was noted between
      groups. Tai Chi significantly lowered blood pressure (systolic -13.33 mmHg;
      diastolic -6.45 mmHg), fasting blood sugar (-0.72 mmol/L), glycated haemoglobin (
      0.39%) and perceived stress (-3.22 score) and improved perceived mental health
      (+4.05 score) and exercise self-efficacy (+12.79 score) at 9 months, compared to
      the control group. In the Tai Chi group, significantly greater reductions in
      blood pressure (systolic -12.46 mmHg; diastolic -3.20 mmHg), fasting blood sugar
      (-1.27 mmol/L), glycated haemoglobin (-0.56%), lower perceived stress (-2.32
      score), and improved perceived mental health (+3.54 score) and exercise self
      efficacy (+12.83 score) were observed, compared to the brisk walking group. No
      significant changes in the other cardiovascular disease risk indicators were
      observed over time between groups. CONCLUSION: Nurses play a key role in
      promoting exercise to reduce cardiovascular disease risk and foster a healthy
      lifestyle among adults. Tai Chi is better than brisk walking in reducing several
      cardiovascular disease risk factors and improving psychosocial well-being, and
      can be recommended as a viable exercise for building a healthy life free of
      cardiovascular disease.

PMID- 30195125
TI  - Family socioeconomic status and maternal depressive symptoms: Mediation through
      household food insecurity across five years.
AB  - RATIONALE: Food insecurity is a significant social problem that has been found to
      co-occur with both poverty and depression. However, few studies have utilized
      longitudinal data to investigate the associations among poverty, depression, and
      food insecurity. OBJECTIVE: This study tested two competing hypotheses, the food
      inadequacy hypothesis and the mental health hypothesis, in examining the
      associations among family socioeconomic status (SES), maternal depression, and
      household food insecurity across children's first five years of life. METHODS:
      Data were drawn from the Early Childhood Longitudinal Study-Birth Cohort (ECLS
      B), a dataset nationally representative of all children born in the United States
      in 2001. Mothers reported family SES and household food insecurity when their
      children were nine months, 24 months, four years, and at kindergarten entry;
      maternal self-rated depressive symptoms were included at nine months, four years,
      and kindergarten entry. RESULTS: An autoregressive cross-lagged model showed that
      family SES was predictive of later household food insecurity, which in turn was
      associated with later maternal depressive symptoms. Significant mediation
      pathways were found with household food insecurity mediating the link between
      family SES and maternal depressive symptoms. CONCLUSIONS: This study highlights
      the need to consider household food insecurity as an underlying mechanism of
      maternal depressive symptoms in under-resourced families. Findings of this study
      can inform public health policy by highlighting the importance of considering
      factors such as food insecurity in the delivery of services to depressed mothers
      and their children in under-resourced contexts, and emphasizing the need for
      coordinated, integrated care in responding to the needs of these high-risk,
      vulnerable families.

PMID- 30195126
TI  - Extended suspect screening strategy to identify characteristic toxicants in the
      discharge of a chemical industrial park based on toxicity to Daphnia magna.
AB  - With an increasing amount of industrial wastewater being discharged and the
      numerous chemicals existed in, methods to identify toxicants in such complex
      matrices are urgently needed for source control and quality management. In vivo
      toxicity to Daphnia magna was evaluated in the effluent of a wastewater treatment
      plant (WWTP). An extended suspect screening strategy was performed by bioassay
      directed fractionation, accompanied with suspect screening of 228 suspect
      chemicals in toxic fractions based on their mass characteristics and
      chromatography characteristics. A toxicity evaluation of the original samples,
      organic components extracted by solid-phase extraction (SPE) and the filtered
      samples showed that organic compounds extracted by SPE were the main toxic
      components. Four of the 26 fractions of the organic extracts exhibited a toxic
      unit (TU) > 1.0, with hydrophobic organic compounds contributing most to the
      toxicity. Twenty-eight of the 228 suspects were identified in four toxic
      fractions, with 53.6% of the suspects elucidated by spectrum interpretation based
      on mass characteristics and 53.8% more false positive suspects removed based on
      chromatography characteristics. Finally, 6 pollutants, including imazalil,
      prometryn, propiconazole, tebuconazole, buprofezin and diazinon, were further
      confirmed and explained 48.79% of the observed toxicity. With 2.48 times more of
      the toxicity explained and 90% of the labor saved, the extended suspect screening
      strategy enabled more efficient and reliable identification compared to
      traditional quantitative analysis and non-target screening, especially for
      identification of characteristic toxicants in complex environmental matrices.

PMID- 30195127
TI  - Lessons learned: Creating an interdisciplinary team and using a nexus approach to
      address a resource hotspot.
AB  - Moving resource management and allocation away from sectoral silos to a paradigm
      founded in integration and leveraging cross-sectoral and trans-disciplinary
      synergies will result in expanded opportunities for economic development and
      improved social well-being (Mohtar, 2017; Mohtar and Daher, 2017). Interventions
      to address complex resource challenges must identify opportunities while
      cognizant of holistic, system level trade-offs (Daher and Mohtar, 2015; Daher et
      al., 2018a, b, c). These interventions must be contextualized locally: Texas has
      spatially varied water scarcity, energy resource abundance, and rapid population
      growth; in the northeastern United States water quality, drainage, and extreme
      weather events pose far greater challenges. While the overall system-of-systems
      quantification of water, energy, food and other interconnected systems remains
      similar across hotspots, the solutions to the challenges posed within each
      hotspot are bound by local knowledge, physical resource constraints, and
      governance challenges. This paper introduces the experience of the Texas A&M
      University Water-Energy-Food Nexus Initiative (WEFNI) in creating a University
      wide, three-year investigatory experience in which an interdisciplinary group
      addressed the resource challenges facing the San Antonio region. This Science of
      the Total Environment (STOTEN) Special Issue documents, in 9 distinct, yet
      complementary, research articles, the multiple dimensions of this resource
      hotspot. This paper reflects on the process of creating interdisciplinary teams
      and presents an overview of the questions and research conducted under thematic
      foci: data and modeling, trade-off analysis, water for food, water for energy,
      and governance. Lessons learned from the interdisciplinary experience are
      presented; potentially transferrable to addressing other resource hotspots within
      the US, and globally.

PMID- 30195128
TI  - Bioavailability of biosolids-borne ciprofloxacin and azithromycin to terrestrial
      organisms: Microbial toxicity and earthworm responses.
AB  - Information on bioavailability of two antibiotic TOrCs, ciprofloxacin (CIP) and
      azithromycin (AZ), to terrestrial organisms is severely limited, especially in
      the biosolids context. Responses of two terrestrial organisms, earthworms and
      microbes, to a range of environmentally relevant concentrations of biosolids
      borne CIP and AZ were assessed in laboratory incubation studies involving 3H
      labeled compounds. Earthworm assessments were based on the Earthworm Sub-chronic
      Toxicity Test (OCSPP 850.3100). Microbial impacts were assessed using respiration
      and reverse transcriptase-quantitative PCR (mRNA) analyses of nutrient (N and P)
      cycling genes as toxicity markers. Antibiotic extractability and stability during
      incubations were assessed using sequential extractions with CaCl2,
      methanol:water, and accelerated solvent extraction and analyses using thin layer
      chromatography. Subsample combustion, in addition to sequential extraction,
      recovered nearly 100% of the added antibiotic. The two compounds persisted
      (estimated half-lives >= 3 y), but extractable fractions (especially of CIP)
      decreased over time. Neither biosolids-borne antibiotic significantly impacted
      overall respiration or N and P cycling. Microbial toxicity responses were
      minimal; complementary DNA (cDNA) concentrations of ammonia oxidizing bacterial
      genes were affected, but only initially. Similarly, earthworms showed no apparent
      response related to toxicity to environmentally relevant (and much greater)
      concentrations of biosolids-borne CIP and AZ. Earthworms, however, accumulated
      both compounds, and the bioaccumulation factor (BAF) values (dry weight basis)
      were ~4 (CIP) and ~7 (AZ) in depurated worms and ~20 (CIP and AZ) in un-depurated
      worms. The microbial and earthworm responses strongly to moderately correlated
      with "bioaccessible" fractions of the target TOrCs. The results suggest that
      biosolids-borne CIP and AZ toxicity to terrestrial microbes and earthworms is
      minimal, but there is a potential for target TOrC entry into ecological food web.

PMID- 30195129
TI  - Selective ionic liquid solvent bar micro-extraction for estimation of ultra-trace
      silver fractions in marine waters.
AB  - Ag can be found in the ocean at the ultra-trace level, mainly as AgCln(n-1)- and
      complexed by dissolved organic matter (Ag-DOM). However, methods for studying Ag
      speciation in marine waters are limited by the lack of extractants capable to
      separate organic and inorganic silver species in natural conditions of seawater
      samples. In this work, a two-phase solvent bar micro-extraction method using the
      ionic liquid trihexyltetradecylphosphonium chloride (Cyphos(r) 101) was applied
      for selective micro-extraction of AgCln(n-1)- from organic silver in marine
      waters, working at seawater pH,. The application to real samples was performed
      under the following conditions: 2.5% Cyphos(r) 101 in kerosene solution with 10%
      dodecan-1-ol inside the fiber, and 30 min of sample extraction at a stirring rate
      of 800 rpm. The proposed SBME was successfully used for estimation of Ag
      fractions in waters from the Bay of Cadiz (South-west Spain) showing its
      applicability for a simple, fast and environmentally friendly speciation of
      silver in marine water samples. The method presented a linear response up to 500
      ng L-1 and a detection limit of 0.4 ng L-1, using GF-AAS for instrumental
      determination.

PMID- 30195130
TI  - An algicidal Streptomyces amritsarensis strain against Microcystis aeruginosa
      strongly inhibits microcystin synthesis simultaneously.
AB  - Microcystis aeruginosa and hepatotoxic microcystins produced by it have posed a
      severe threat to aquatic ecological security and human health. In this study a
      Streptomyces amritsarensis HG-16, showing high algicidal activity against M.
      aeruginosa and strong inhibitory effect on microcystin synthesis, was obtained by
      screening some anti-Fusarium sp. microbial strains isolated before in our
      laboratory. HG-16 bound cyanobacterial cells by mycelia to form flocs and killed
      M. aeruginosa by secreting active substances, which were proteinase K resistant
      and stable in the temperature range of 35-75  degrees C and pH range of 3-11. HG
      16 removed M. aeruginosa of 105 and 106 cell mL-1 cell densities in similar rate
      and was active against all the tested harmful unicellular and filamentous
      cyanobacteria. Results of differential gene expression analysis indicated that HG
      16 affected the photosynthesis system and microcystin synthesis of M. aeruginosa.
      Accordingly, the algicidal activity of HG-16 was light-dependent, and microcystin
      synthesis of M. aeruginosa decreased by 91.2% with HG-16 treatment. Thus, it is
      promising to utilize HG-16 to mitigate harmful cyanobacterial blooms, inhibit
      microcystin synthesis and control plant disease caused by Fusarium.spp. through
      irrigating farmland with eutrophic water applied HG-16.

PMID- 30195131
TI  - Inhalation bioaccessibility of PAHs in PM2.5: Implications for risk assessment
      and toxicity prediction.
AB  - In this study, 46 PM2.5 samples collected from Nanjing, China were analyzed for
      total PAH concentration, with 14 samples assessed for PAH inhalation
      bioaccessibility and dioxin toxicity. The concentration of 19 PAH compounds in
      PM2.5 ranged from 4.03 to 102 ng m-3. When PAH inhalation bioaccessibility was
      assessed using simulated epithelial lung fluid, mean bioaccessibility values
      ranged from 3.21% (Benzo(c)fluorene) to 44.2% (Acenaphthylene). Benzo(a)pyrene
      concentration in 50% of the PM2.5 samples exceeded the Chinese air quality
      standard of 2.5 ng m-3, however, when bioaccessibility was considered, all
      samples were below the criterion. Similarly, the cancer risk probability for all
      PM2.5 samples was >10-4 incidences on the basis of total PAH concentration, while
      only 37% of samples posed a risk >10-4 after incorporation of bioaccessibility.
      Dioxin toxicity of PM2.5-bound PAHs was also investigated by characterizing mRNA
      expression of cytochrome P450 superfamily members in human lung cells (A549
      cell). Compared to total PAH concentration, the use of bioaccessible
      concentration was better at predicting dioxin toxicity of PM2.5-associated PAHs
      (correlation coefficient R2 = 0.40-0.83 with p < 0.05). This study indicates that
      PAH inhalation bioaccessibility is an important consideration when assessing and
      predicting the risk posed by PM2.5 particles, which is particularly important for
      countries with deteriorating air quality.

PMID- 30195132
TI  - Respiratory symptoms, asthma and levels of fractional exhaled nitric oxide in
      schoolchildren in the industrial areas of Estonia.
AB  - OBJECTIVES: Exposure to air pollutants in the ambient environment has been
      associated with various respiratory symptoms, and with increased asthma
      diagnosis, in both children and adults. Most research to date has focussed on
      core pollutants, such as PM10, PM2.5, SO2 and NO2, and less attention has been
      given to the effects of industry-specific contamination. The current study aimed
      to examine the associations between respiratory symptoms, asthma, increased
      levels of fractional exhaled nitric oxide (FeNO) (as a marker of eosinophilic
      airway inflammation) and ambient levels of industrial pollutants (such as
      benzene, phenol, formaldehyde and non-methane hydrocarbons) for schoolchildren
      living near oil shale industries in Ida-Viru County, Estonia. METHODS: A total of
      1326 schoolchildren from Ida-Viru, Laane-Viru and Tartu Counties participated in
      a cross-sectional study, consisting of questionnaires on respiratory symptoms and
      asthma, as well as clinical examinations to measure FeNO. Dispersion modelling
      was used to characterize individual-level exposure to industrial air pollutants
      at each subject's home address. Associations between exposure and respiratory
      health were investigated using logistic regression analysis, and differences in
      results between regions were analysed using the Chi-squared test. RESULTS: The
      prevalence of respiratory symptoms (p < 0.05) in children living near (i.e.
      within 5 km) of an oil shale industry site in Ida-Viru County was 2-4 times
      higher than in children living in the reference area of Tartu County. Children
      exposed to 1 MUg/m3 higher levels of benzene and formaldehyde had a higher odds
      ratio (OR) of having rhinitis without a cold (OR 1.03, 95% confidence interval
      (CI) 1.01-1.06), of ever having had attacks of asthma (OR 1.05, 95% CI 1.01-1.10)
      and of having a dry cough a few days per year (OR 1.05, 95% CI 1.01-1.10).
      Children exposed to 1 MUg/m3 higher levels of benzene, formaldehyde, phenol and
      non-methane hydrocarbons had a higher odds ratio of having high FeNO levels (>=30
      ppb): OR and 95% CI of 1.05, 1.01-1.09; 1.22, 1.06-1.41; 1.01, 1.00-1.01; and
      1.75, 1.75-2.62, respectively.

PMID- 30195133
TI  - Biogeomorphological processes in an arid transgressive dunefield as indicators of
      human impact by urbanization.
AB  - Urban and tourist developments can have long-lasting impacts on coastal
      environments and fundamentally alter the evolution of coastal dune systems. This
      is the case of the Maspalomas dunefield (Gran Canaria, Canary Islands), hosting
      one of the largest tourist resorts in Spain. The resort was built on top of a
      sedimentary terrace at 25 m above sea level (El Ingles) in the 1960s, and has
      subsequently affected local winds and therefore aeolian sediment transport
      patterns. Buildings on the terrace deflect the winds to the south of the
      dunefield, where the rate of sediment transport accelerated. A shadow zone
      appeared to the lee side of the resort with a consequent decrease in wind speed
      and aeolian sediment transport and an increase in vegetation cover. In this
      paper, first we characterize the environmental changes around El Ingles terrace
      in recent decades, and describe the changes in the shadow zone through an
      analysis of the evolution of sedimentary volumes and vegetation characteristics
      (density, spatial patterns, and plants communities). A series of historical
      aerial photographs, recent orthophotos and digital elevation models obtained by
      digital photogrammetry and LiDAR, as well as fieldwork were used to characterize
      plant communities and spatial-temporal changes in erosive landforms. Results show
      changes in the pattern and migration rates of dunes located at the southern edge
      of the urbanization, as well as the formation of blowouts and large deflation
      areas, where the vegetation increases in density and number of plant communities.
      We discuss eco-anthropogenic factors that have produced these environmental
      changes.

PMID- 30195134
TI  - Net N2O production from soil particle size fractions and its response to changing
      temperature.
AB  - Previous studies demonstrated that finer soil particles have smaller rates of CO2
      emission but larger Q10 values (the proportionate increase in the rate for a
      warming of 10  degrees C) than coarser particles. However, it has not been tested
      whether there is a regular pattern for rates and Q10 for N2O emission (net
      production) across soil particle size fractions, considering the known positive
      correlation between soil CO2 and N2O emissions. A short-term incubation study
      with different soil particle fractions was conducted for soils from a grassland,
      a forest, an upland (including organic manure (OM) and chemical nitrogen,
      phosphorus, and potassium fertilizers (NPK) treatments), and a paddy (including
      manure plus chemical fertilizer (MNPK) and NPK treatments) under a series of
      increasing and decreasing temperatures between 5  degrees C and 30  degrees C
      with 5  degrees C intervals. For all the soils, net N2O production per unit mass
      of soil N was smaller from the silt (2-50 MUm) fraction than from the sand (>50
      MUm) and clay (<2 MUm) fractions. In paddy soils, Q10 for net N2O production was
      highest from the clay fraction. In contrast, Q10 was highest in the sand fraction
      for the grassland soil. In the upland and paddy soils, the rates of net N2O
      production were higher in OM or MNPK treatment than in their corresponding NPK
      treatment, but Q10 values were similar between the manure and NPK treatments. The
      net N2O production rates positively correlated with CO2 emission across all soil
      samples, and this was also the case for their Q10 values. Q10 values for net N2O
      production averaged 8% lower than those for CO2 emissions. In conclusion, the net
      N2O production rates appear to be the smallest from the silt fraction.

PMID- 30195135
TI  - Cortical tracking of constituent structure in language acquisition.
AB  - Linguistic units are organized at multiple levels: words combine to form phrases,
      which combine to form sentences. Ding, Melloni, Zhang, Tian, and Poeppel (2016)
      discovered that the brain tracks units at each level of hierarchical structure
      simultaneously. Such tracking requires knowledge of how words and phrases are
      structurally related. Here we asked how neural tracking emerges as knowledge of
      phrase structure is acquired. We recorded electrophysiological (MEG) data while
      adults listened to a miniature language with distributional cues to phrase
      structure or to a control language which lacked the crucial distributional cues.
      Neural tracking of phrases developed rapidly, only in the condition in which
      participants formed mental representations of phrase structure as measured
      behaviorally. These results illuminate the mechanisms through which abstract
      mental representations are acquired and processed by the brain.

PMID- 30195136
TI  - Comprehenders model the nature of noise in the environment.
AB  - In everyday communication, speakers make errors and produce language in a noisy
      environment. Recent work suggests that comprehenders possess cognitive mechanisms
      for dealing with noise in the linguistic signal: a noisy-channel model. A key
      parameter of these models is the noise model: the comprehender's implicit model
      of how noise affects utterances before they are perceived. Here we examine this
      noise model in detail, asking whether comprehension behavior reflects a noise
      model that is adapted to context. We asked readers to correct sentences if they
      noticed errors, and manipulated context by including exposure sentences
      containing obvious deletions (A bystander was rescued by the fireman in the nick
      time.), insertions, exchanges, mixed errors, or no errors. On test sentences (The
      bat swung the player.), participants' corrections differed depending on the
      exposure condition. The results demonstrate that participants model specific
      types of errors and make inferences about the intentions of the speaker
      accordingly.

PMID- 30195137
TI  - Impact of data aggregation approaches on the relationships between operating
      speed and traffic safety.
AB  - The impact of operating speed on traffic crash occurrence has been a
      controversial topic in the traffic safety discipline as some studies reported a
      positive association whereas others indicated a negative relationship between
      speed and crashes. Two major issues thought to be accountable for such
      conflicting findings are the application of inappropriate statistical methods and
      the use of sample datasets with varying levels of aggregation. The main objective
      of this study is therefore to investigate the impacts of data aggregation schemes
      on the relationships between operating speed and traffic safety. A total of three
      aggregation approaches were examined: (1) a segment-based dataset in which
      crashes are grouped by roadway segment, (2) a scenario-based dataset where
      crashes are aggregated by traffic operating scenarios, and (3) a disaggregated
      crash-level dataset consisting of information from individual crashes. The first
      two aggregation approaches were used in examining the relationships between
      operating speed and crash frequency using Bayesian random-effects negative
      binomial models. The third disaggregated crash risk analysis was conducted
      utilizing Bayesian random-effects logistic regression models. From the modeling
      results, it has been concluded that the scenario-based approach shared similar
      findings with those of the disaggregated crash risk analysis approach in which a
      U-shaped relationship between operating speed and crash occurrence was
      identified. However, the commonly adopted segment-based aggregation approach
      revealed a monotonous negative relationship between speed and crash frequency.
      The implications of the different analyses results and the potential applications
      of the results on speed management systems have therefore been discussed.

PMID- 30195138
TI  - Maternal mortality after cesarean section in the Netherlands.
AB  - OBJECTIVES: Maternal mortality is rare in high-resource settings. This hampers
      studies of the association between maternal mortality and mode of birth, although
      this topic remains of importance, given the changing patterns in mode of birth
      with increasing cesarean section rates in most countries. Purpose of this study
      was to examine incidence of cesarean section-related maternal mortality in the
      Netherlands and association of surgery with the chain of morbid events leading to
      death. STUDY DESIGN: We performed a retrospective cohort study using the
      Confidential Enquiry into Maternal Deaths, including all 2,684,946 maternities in
      the Netherlands between January 1st, 1999, and December 31st, 2013, registered in
      the Dutch Perinatal Registry. All available medical records of cases reported to
      the Dutch Maternal Mortality and Severe Morbidity Audit Committee were assessed
      by two researchers, and one or two additional experts in case of contradicting
      opinions, based on a set of pre-identified clinical criteria. Main outcome
      measures were (1) incidence and relative risk of maternal death following
      cesarean section and vaginal birth and (2) incidence of death directly related to
      cesarean section and death in which cesarean section was one of the contributing
      factors. RESULTS: Risk of death after cesarean section was 21.9 per 100.000
      cesarean sections (86/393,443) versus 3.8 deaths per 100.000 vaginal births
      (88/2,291,503): Relative Risk (RR) 5.7 (95% Confidence Interval [CI] 4.2-7.7).
      Death directly related to complications of cesarean section occurred in 8/86
      women: 2 per 100,000 cesarean sections. With addition of 43 women in which
      cesarean section did not initiate, but contributed to the chain of events leading
      to mortality, risk of death increased to 13 per 100,000 cesarean sections
      (51/393,443; RR 3.4; 95%CI 2.4-4.8). At the start of cesarean section, pre
      existing morbidity was present in 70/86 women (81.4%). CONCLUSIONS: Compared to
      vaginal birth, maternal mortality after cesarean section was three times higher
      following exclusion of deaths that had no association with surgery. In
      approximately one in ten deaths after cesarean section, surgery did in fact
      initiate the chain of morbid events.

PMID- 30195140
TI  - Immunomodulatory properties of chitosan polymers.
AB  - The introduction of vaccines is regarded as one of the most successful medical
      interventions to date. However, there is a clear need for the development of new
      vaccines for diseases which require the induction of a potent cellular immune
      response. Advancements in the field of vaccine research have resulted in a move
      away from the use of whole organisms and towards the use of subunit vaccines
      which consist of highly purified antigens with an improved safety profile.
      Adjuvants are immunostimulatory components that are included in subunit vaccine
      formulations to help direct and amplify adaptive immune responses. Chitosan is a
      cationic polysaccharide that has been examined in an adjuvant setting due to its
      biocompatible and biodegradable nature. The polysaccharide has been shown to have
      the capacity to induce Th1 cell responses following vaccination by injection or
      mucosal routes, supporting its application as an alternative to alum for vaccines
      that promote cell-mediated immunity. Here, we provide an overview of the physico
      chemical properties of chitosan with a focus on the specific characteristics that
      dictate the type and scale of the immune responses induced. The potential to
      finely tailor chitosan polymers in order to direct specific types of immune
      responses can provide invaluable tools for the design of novel chitosan-based
      adjuvants and biomaterials.

PMID- 30195139
TI  - Calcium ameliorates the toxicity of sulfate salinity in Brassica rapa.
AB  - Salinity stress in Brassica, often only associated with osmotic effects and the
      toxicity of Na+, was more severe when applied as Na2SO4 than as NaCl, indicating
      that SO42- ions had toxic effects as well. Application of 10 mM calcium in the
      form of CaCl2 in the growth medium of plants only slightly ameliorated growth
      impairment by NaCl and KCl, but almost completely prevented negative effects of
      Na2SO4 and K2SO4 on plant biomass production. This effect was calcium specific,
      as MgCl2 ameliorated sulfate toxicity to a much lower extent. This sulfate
      toxicity coincided with a strong decrease in the plant content of calcium and
      manganese upon sulfate salinity. Application of CaCl2 largely alleviated this
      decrease, however, it did not prevent the higher tissue concentration of sulfate.
      CaCl2 prevented the increase in organic sulfur compounds presumably by reducing
      of relative gene expression of ATP-sulfurylase (ATPS) and adenosine 5'
      phosphosulfate reductase (APR) indicating a possible regulation of sulfate
      assimilation by calcium. The upregulation of the genes encoding for Group 4
      sulfate transporters (Sultr4;1 and 4;2) upon sulfate salinity, was absent in the
      presence of CaCl2. Therefore, additional calcium may facilitate an increased
      vacuolar capacity for sulfate accumulation.

PMID- 30195141
TI  - The transient receptor potential cation channel subfamily V members 1 and 2, P2X
      purinoceptor 3 and calcitonin gene-related peptide in sensory neurons of the rat
      trigeminal ganglion, innervating the periosteum, masseter muscle and facial skin.
AB  - OBJECTIVE: Distribution of the transient receptor potential cation channel
      subfamily V members 1 (TRPV1) and 2 (TRPV2), and P2X purinoceptor 3 (P2 * 3) was
      investigated in rat trigeminal ganglion neurons innervating the periosteum,
      masseter muscle and facial skin. DESIGN: Double immunofluorescence method for
      TRPV1 and TRPV2 ion channels or ATP receptor P2 * 3 with calcitonin gene-related
      peptide (CGRP) was performed on trigeminal ganglion neurons retrogradely labeled
      from the mandibular periosteum, masseter muscle, or facial skin in 15 male Wistar
      rats. RESULTS: The cell size of periosteum neurons (mean +/- S.D. = 810.7 +/-
      36.1 MU m2) was smaller than that of masseter muscle neurons (927.0 +/- 75.6 MU
      m2), and larger than that of facial skin neurons (661.3 +/- 82.2 MU m2).
      Periosteum neurons contained TRPV1- (26.7%), TRPV2- (47.1%) and P2 * 3
      immunoreactivity (50.1%). Expression of TRPV2-immunoreactivity was more abundant
      among periosteum neurons than among facial skin neurons (16.1%). Regarding to
      TRPV1 and P2 * 3 expression, however, there was no significant difference between
      periosteum neurons and, masseter muscle and facial skin neurons. TRPV1-
      immunoreactive trigeminal ganglion neurons which innervated the periosteum,
      masseter muscle and facial skin mostly had small and medium-sized cell bodies,
      whereas TRPV2- and P2 * 3-immunoreactive trigeminal ganglion neurons innervating
      those tissues were of various cell body sizes. Approximately 20% of periosteum
      (19.2%), masseter muscle (19.2%) and facial skin (21.5%) neurons contained both
      TRPV1- and CGRP-immunoreactivity. Some periosteum neurons also co-expressed CGRP
      immunoreactivity with TRPV2- (10.9%) or P2 * 3- immunoreactivity (11.1%).
      Distributions of perivascular and free nerve fibers containing CGRP and either
      TRPV1, TRPV2, or P2 * 3 were occasionally very similar in the mandibular
      periosteum. CONCLUSIONS: The present study indicated that trigeminal ganglion
      nociceptors innervating the periosteum as well as those innervating the masseter
      muscle and facial skin have vanilloid, acidic, thermal, mechanical and ATP
      sensors. In some periosteum neurons, CGRP may act as inflammatory mediator
      through activation of TRPV1, TRPV2 and P2 * 3.

PMID- 30195142
TI  - Overexpression of T-cadherin inhibits the proliferation of oral squamous cell
      carcinoma through the PI3K/AKT/mTOR intracellular signalling pathway.
AB  - OBJECTIVE: To evaluate T-cadherin gene expression in patients with oral squamous
      cell carcinoma(OSCC) and explore its effect on the proliferation of OSCC.
      Additionally, the present study aimed to determine whether the anti-proliferative
      effect of T-cadherin was associated with the phosphoinositide 3-kinase
      (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) signaling
      pathway. DESIGN: A reverse transcription-quantitative polymerase chain reaction
      was performed to detect T-cadherin mRNA expression. A Cell Counting Kit-8 (CCK-8)
      assay was used to investigate the effect of T-cadherin on cellular proliferation.
      The survival curves were plotted by Kaplan-Meier method, and the differences
      between subgroups were determined by log-rank test. The protein expression of
      phosphorylated (p)-PI3K, total PI3K, p-AKT, total AKT, p-mTOR, total mTOR and
      cyclin D1was assessed using western blot. RESULTS: It was revealed that the
      expression of T-cadherin mRNA was significantly decreased in OSCC samples
      compared with normal adjacent ones (P = 0.007), and that low T-cadherin
      expression was correlated with advanced clinical stage (P = 0.0249), higher
      pathological grade (P = 0.0288) and poor differentiation (P = 0.0295) of OSCC. In
      addition, T-cadherin negative expression was revealed to be associated with a
      worse progression-free survival (PFS) in patients with OSCC. Furthermore, the
      overexpression of T-cadherin inhibited the proliferation of OSCC cell lines and
      suppressed the PI3K/AKT/mTOR signaling pathway. Importantly, the combined
      treatment of T-cadherin with the PI3K inhibitor LY294002 enhanced the inhibitory
      effect of T-cadherin on cellular proliferation and the PI3K/AKT/mTOR pathway.
      CONCLUSIONS: The results of the present study suggested that T-cadherin may
      function as a tumor suppressor gene in OSCC through suppressing the PI3K/AKT/mTOR
      pathway, and that it may be a potential therapeutic target for OSCC.

PMID- 30195143
TI  - Differential cellular composition of human palatine and pharyngeal tonsils.
AB  - OBJECTIVE: The goal of this study was to gain a better understanding of the
      potential functional specialization of palatine and pharyngeal tonsils, by
      comparing their cellular composition in paired specimens from a large cohort of
      adenotonsillectomy patients. DESIGN: Resident B cell, T cell, dendritic cell, and
      stromal cell subsets were characterized using multicolor flow cytometry in
      palatine and pharyngeal tonsil specimens from 27 patients, age 2-34 years.
      RESULTS: Paired comparisons showed highly significant intra-individual
      differences in resident cell subsets of palatine and pharyngeal tonsils. Palatine
      tonsils harbored higher fractions of germinal center B cells/plasmablasts and IgD
      CD27- double-negative B cells, and conversely lower fractions of IgD + CD38-
      resting naive B cells compared to pharyngeal tonsils. Palatine tonsils also
      showed lower fractions of plasmacytoid dendritic cells, and higher percentages of
      two subsets of stromal cells - fibroblastic reticular cells and lymphatic
      endothelial cells - compared to pharyngeal tonsils from the same individual.
      CONCLUSIONS: Despite their physical proximity and histological similarities,
      palatine and pharyngeal tonsils display marked intra-individual differences in
      their cellular composition with regard to functionally important immune and
      stromal subsets. These differences are likely to have immunologic, pathologic,
      and physiologic significance.

PMID- 30195144
TI  - Absolute pitch is not necessary for pitch class-color synesthesia.
AB  - Sounds evoke color sensations in sound-color synesthesia. Recently, we showed
      that pitch classes (do, re, mi, etc.) have rainbow hues and that colors are
      linked to the names of pitch classes rather than to their sounds in 15 subjects
      who had "pitch class-color synesthesia." However, all synesthetes in our previous
      study had high levels of absolute pitch (AP); therefore the effects of AP on the
      condition remained unclear. The present study investigated 18 additional pitch
      class-color synesthetes who had no or lower levels of AP, and confirmed the
      generality of the above findings. Furthermore, behavioral experiments indicated a
      two-step process underlying color sensations: pitches are first associated with
      their pitch class names, and then the pitch class names evoke color sensations.
      Two separable brain functions underlie pitch-to-color conversion in pitch class
      color synesthesia: a musical function of pitch class identification, and the
      synesthetic association between pitch class and color.

PMID- 30195145
TI  - Mean platelet volume and long-term cardiovascular outcomes in patients with
      stable coronary artery disease.
AB  - BACKGROUND AND AIMS: Although an elevated mean platelet volume (MPV) has been
      associated with poor clinical outcomes after acute coronary syndrome (ACS), the
      association between MPV and long-term outcomes in patients with stable coronary
      artery disease (CAD) remains uncertain. We aimed to investigate the impact of pre
      procedural MPV levels in patients following elective percutaneous coronary
      intervention (PCI). METHODS: We studied 2872 stable CAD patients who underwent
      their first PCI and who had available data on pre-procedural MPV between 2002 and
      2016. Patients were divided into quartiles based on their MPV. The incidences of
      major adverse cardiac events (MACE), including all-cause death and non-fatal
      myocardial infarction, were evaluated. RESULTS: The median MPV was 10.4 fL
      (interquartile range: 9.8-11.0). During a median follow-up of 5.6 years, 498
      (17.3%) MACE were identified, with a cumulative incidence significantly higher in
      the lowest MPV group than in other groups (p < 0.01). After adjustment for
      platelet count and the other cardiovascular risk factors, the lowest MPV group
      had a significantly higher risk of MACE compared with the highest MPV groups
      (hazard ratio: 1.43, 95% confidence interval 1.10-1.86, p = 0.009). Decreasing
      MPV as a continuous variable was associated with the incidence of MACE (hazard
      ratio: 1.16 per 1 fL decrease, 95% confidence interval 1.04-1.30, p = 0.007).
      CONCLUSIONS: Contrary to previous studies on ACS patients, this study showed that
      a low MPV was associated with worse clinical outcomes among stable CAD patients.

PMID- 30195146
TI  - Complement activation associated with ADAMTS13 deficiency may contribute to the
      characteristic glomerular manifestations in Upshaw-Schulman syndrome.
AB  - INTRODUCTION: Upshaw-Schulman syndrome (USS) is a congenital form of thrombotic
      thrombocytopenic purpura (TTP) associated with loss-of-function mutations in the
      ADAMTS13 gene, possibly leading to aberrant complement activation and vascular
      injury. However, USS is extremely rare, and there have been no systematic studies
      correlating histopathological severity with local ADAMTS13 expression and
      complement activation. MATERIALS AND METHODS: Here, we compared histopathological
      features, ADAMTS13 immunoreactivity, and immunoreactivity of complement proteins
      C4d and C5b-9 among renal biopsy tissues from five USS cases, ten acquired TTP
      cases, and eleven controls. RESULTS: Pathological analysis revealed chronic
      glomerular sclerotic changes in the majority of USS cases (4 of 5), with minor
      glomerular pathology in the remaining case. In two of these four severe cases,
      more than half of the glomerular segmental sclerosis area was localized in the
      perihilar region. The average number of ADAMTS13-positive cells per glomerulus
      was significantly lower in USS cases than controls (p < 0.05). Conversely, C4d
      staining was significantly more prevalent in the glomerular capillary walls of
      USS cases than controls (p < 0.05), while C5b-9 staining did not differ
      significantly among groups. CONCLUSIONS: These findings suggest that the severity
      of glomerular injury in USS is associated with deficient ADAMTS13 expression and
      local complement activation, particularly in vascular regions with higher
      endothelial shear stress. We suggest that C4d immunostaining provides evidence
      for complement-mediated glomerular damage in USS.

PMID- 30195147
TI  - Biosorptive removal of Zn(II) ions by Pongamia oil cake (Pongamia pinnata) in
      batch and fixed-bed column studies using response surface methodology and
      artificial neural network.
AB  - Design of experiment and artificial neural networks (ANN) have been effectively
      employed to predict the rate of uptake of Zn(II) ions onto defatted pongamia oil
      cake. Four independent variables such as, pH (2.0-7.0), initial concentration of
      Zn(II) ions (50-500 mg/L), temperature (30oC-50  degrees C), and dosage of
      biosorbent (1.0-5.0 g/L) were used for the batch mode while the three independent
      variables viz. flowrate, initial concentration of Zn(II) ions and bed height were
      employed for the continuous mode. Second-order polynomial equations were then
      derived to predict the Zn(II) ion uptake rate. The optimum conditions for batch
      studies was found to be pH: 4.45, metal ion concentration: 462.48 mg/L, dosage:
      2.88 g/L, temperature: 303 K and on the other hand the column studies flow rate:
      5.59 mL/min, metal ion concentration: 499.3 mg/L and bed height: 14.82 cm. Under
      these optimal condition, the adsorption capacity was 80.66 mg/g and 66.29 mg/g
      for batch and column studies, respectively. The same data was fed to train a feed
      forward multilayered perceptron, using MATLAB to develop the ANN based model. The
      predictive capabilities of the two methodologies were compared, by means of the
      absolute average deviation (AAD) (4.57%), model predictive error (MPE) (4.15%),
      root mean square error (RMSE) (3.19), standard error of prediction (SEP) (4.23)
      and correlation coefficient (R) (0.99) for ANN and for RSM AAD (16.27%), MPE
      (21,25%), RMSE (13.15%), SEP and R (0.96) by validation data. The findings
      suggested that compared to the prediction ability of RSM model, the properly
      trained ANN model has better prediction ability. In batch studies, equilibrium
      data was used to determine the isotherm constants and first and second order rate
      constants. In column, bed depth service time (BDST) and Thomas model was used to
      fit the obtained column data.

PMID- 30195148
TI  - Collision and displacement vulnerability to offshore wind energy infrastructure
      among marine birds of the Pacific Outer Continental Shelf.
AB  - Marine birds are vulnerable to collision with and displacement by offshore wind
      energy infrastructure (OWEI). Here we present the first assessment of marine bird
      vulnerability to potential OWEI in the California Current System portion of the
      U.S. Pacific Outer Continental Shelf (POCS). Using population size, demography,
      life history, flight heights, and avoidance behavior for 62 seabird and 19 marine
      water bird species that occur in the POCS, we present and apply equations to
      calculate Population Vulnerability, Collision Vulnerability, and Displacement
      Vulnerability to OWEI for each species. Species with greatest Population
      vulnerability included those listed as species of concern (e.g., Least Tern
      [Sternula antillarum], Marbled Murrelet [Brachyramphus marmoratus], Pink-footed
      Shearwater [Puffinus creatopus]) and resident year-round species with small
      population sizes (e.g., Ashy Storm-Petrel [Oceanodroma homochroa], Brandt's
      Cormorant [Phalacrocorax penicillatus], and Brown Pelican [Pelecanus
      occidentalis]). Species groups with the greatest Collision Vulnerability included
      jaegers/skuas, pelicans, terns and gulls that spend significant amounts of time
      flying at rotor sweep zone height and don't show macro-avoidance behavior
      (avoidance of entire OWEI area). Species groups with the greatest Displacement
      Vulnerability show high macro-avoidance behavior and low habitat flexibility and
      included loons, grebes, sea ducks, and alcids. Using at-sea survey data from the
      southern POCS, we combined species-specific vulnerabilities described above with
      at-sea species densities to assess vulnerabilities spatially. Spatial
      vulnerability densities were greatest in areas with high species densities (e.g.,
      near-shore areas) and locations where species with high vulnerability were found
      in abundance. Our vulnerability assessment helps understand and minimize
      potential impacts of OWEI infrastructure on marine birds in the POCS and could
      inform management decisions.

PMID- 30195149
TI  - Effects of frutalin and doxorubicin on growth, ultrastructure and gene expression
      in goat secondary follicles cultured in vitro.
AB  - This study evaluated the effects of frutalin (0.6, 6.0 or 60.0 MUg/mL) and
      doxorubicin (0.3 MUg/mL) on survival, growth and ultrastructure of in-vitro
      cultured goat secondary follicles. The effects of these substances on the levels
      of mRNA for Casp3, Casp6, Bax, and Bcl2 were also investigated. Results showed
      that, after 6 days of culture, frutalin or doxorubicin reduced the percentage of
      normal follicles (P < 0.05), but doxorubicin had higher toxicity than frutalin.
      Except for follicles cultured with 0.6 MUg/mL frutalin, follicular growth rate
      was reduced after culture with doxorubicin or frutalin (P < 0.05). The presence
      doxorubicin or 60.0 MUg/mL frutalin increased the levels of mRNA for Casp3,
      Casp6, Bax, and Bcl2 (P < 0.05). Higher mRNA levels for Casp3, Casp6 and Bax were
      found in follicles cultured with doxorubicin, but higher levels of Bcl2 mRNA were
      found in follicles cultured with frutalin (P < 0.05). In conclusion, frutalin has
      lower toxic effects than doxorubicin on secondary follicles cultured in vitro.

PMID- 30195150
TI  - Microbial exposure and human health.
AB  - The human body comprises of micro-ecosystem made up of trillions of microbes
      (i.e. bacteria, archaea, fungi, protists and viruses). The total microbial gene
      content, which is referred to as the human microbiome, is fundamental to human
      physiology and immunity. There exists an intricate relationship between the
      surrounding microbial world (i.e. the environment) and the endogenous human
      microbiome, mediated by the immune system. Disrupting this relationship can a
      profound effect on human health and disease. Understanding how microbial exposure
      influences immune response and the feedback on endogenous microbial metabolic
      activity could have profound implications for the development of novel microbial
      therapeutics. The term 'microbial exposure' is used generally to refer to
      exogenous environmental microbial interaction, while 'exposome' accounts for both
      the environmental exposures and the impact of lifestyle-associated microbial
      impacts, such as diet influences on endogenous microbial metabolism. In this
      review, we focus on how environment and lifestyle-associated microbial exposures
      shape the human immune system and microbiome, and how the resulting changes can
      shape human health, especially during critical developmental windows, that is
      prenatal, postnatal and adult. We conclude this review by proposing approaches to
      characterize the microbial exposome so as to accelerate the development of a
      precision microbial therapeutics for both practical and clinical intervention.

PMID- 30195151
TI  - Genetic polymorphism analysis of 40 Y-chromosomal STR loci in seven populations
      from South China.
AB  - China is a multi-ethnic country. Due to its diverse terrain, many ethnic groups
      are geographically isolated within China. This phenomenon is especially prevalent
      in southern China. As Y-STR loci are paternally inherited, they can be used to
      effectively understand the genetic relationship between different populations and
      thus aid in forensic science. In this study, forty Y-STR loci were analysed in
      2018 unrelated male individuals from the following seven ethnic populations in
      South China: Yao (n=147), Zhuang (n=225), Gelao (n=156), Miao (n=186), Maonan
      (n=133), Gin (n=160) and Guangxi Han (n=1011). Using both AGCU Y24 STR and GFS
      Y24 STR genotyping kits, a total of 335 alleles and 141 haplotypes of three multi
      copy loci were observed in these seven populations. The highest GD value of the
      40 Y-STR loci in the overall population was 0.9643 for DYS385a/b, while the
      lowest was 0.4101 for DYS438. Out of the 2018 samples analysed, 1935 distinct
      haplotypes and 1858 unique haplotypes were observed. The HD value of the total
      samples was up to 0.9994 and ranged from a low of 0.9908 in the Yao to a high of
      0.9999 in the Han population. We found using population structure analysis that
      the genetic distance is smaller among the seven southern populations (Guangxi
      Han, Gelao, Yao, Miao, Zhuang, Jing and Maonan) than the northern populations
      (Tibetan, Korean, Mongolian, Uygur and Hui). We show that the 40 Y-STRs have a
      high level of polymorphism in the South China ethnic groups and there is a high
      degree of differentiation among ethnic groups located in geographically
      distributed and densely populated areas. These data may provide additional
      resources for forensic applications and population genetic studies.

PMID- 30195152
TI  - Visualising latent DNA on swabs.
AB  - Collection for touch DNA either at scenes or on items submitted to a forensic
      laboratory is based on assumptions as to where a person made direct contact. In
      many instances a swab may be applied to an area where no contact has been made.
      Many swabs may therefore be submitted for DNA profiling on which no DNA is
      present, resulting in the loss of both time and resources by analysing such
      swabs. This study has developed a simple, fast, DNA-staining and fluorescence
      microscopy-based screening method for swabs to indicate if there is any DNA from
      which to generate a profile. Ten different types of swabs were tested covering
      the major types used (foam, cotton and nylon). Each swab was treated by: no
      addition of dye or DNA, addition of dye only, addition of known DNA and addition
      of dye and DNA. The stain used was DiamondTM Nucleic Acid Dye (DD) and
      fluorescence microscopy was achieved with a digital microscope equipped with a
      blue LED light source (480nm) for excitation and an emission filter of 510nm. Two
      types of samples were tested, either buccal swabs or swabs collected from areas
      touched by volunteers and all analyses were performed in triplicate. The samples
      were collected and retained at room temperature with time intervals of 0 day, 7
      days, 14 days, 21 days, and 28 days before detection using DD staining and
      fluorescence microscopy. Seven of the swab types used were found to be unsuitable
      due to the lack of any difference in the fluorescence detected when no DNA, or
      only the dye, or a combination of DNA and dye were added. Three swab types (black
      cotton swab, Ultrafine dental applicator, and Cylinder dental applicator) were
      found to be much more effective for collection of DNA. Further, stained cellular
      material retained its fluorescence for up to 4 weeks and swabs containing
      cellular material that had been stored for four weeks could be stained and
      visualised. Additionally, DD did not affect DNA profiling. This screening method
      has the potential to be a routine step in a forensic laboratory to save costs of
      processing samples where swabs are devoid of any DNA. This technique is rapid,
      easy, cheap, non-destructive and safe.

PMID- 30195153
TI  - Signal transduction via integrin adhesion complexes.
AB  - Integrin adhesion complexes (IACs) have evolved over millions of years to
      integrate metazoan cells physically with their microenvironment. It is presumed
      that the simultaneous interaction of thousands of integrin receptors to binding
      sites in anisotropic extracellular matrix (ECM) networks enables cells to
      assemble a topological description of the chemical and mechanical properties of
      their surroundings. This information is then converted into intracellular signals
      that influence cell positioning, differentiation and growth, but may also
      influence other fundamental processes, such as protein synthesis and energy
      regulation. In this way, changes in the microenvironment can influence all
      aspects of cell phenotype. Current concepts envisage cell fate decisions being
      controlled by the integrated signalling output of myriad receptor clusters, but
      the mechanisms are not understood. Analyses of the adhesome, the complement of
      proteins attracted to the vicinity of IACs, are now providing insights into some
      of the primordial links connecting these processes. This article reviews recent
      advances in our understanding of the composition of IACs, the mechanisms used to
      transduce signals through these junctions, and the links between IACs and cell
      phenotype.

PMID- 30195155
TI  - The psychological wellbeing benefits of place engagement during walking in urban
      environments: A qualitative photo-elicitation study.
AB  - The psychological wellbeing potential of walking in urban environments has
      received limited attention from scholars, despite the important public health
      implications of identifying characteristics of urban settings that support
      wellbeing and encourage behaviour change. The study is the first to explore
      psychological wellbeing experiences of urban walking framed by theories of
      restorative environments and therapeutic landscape. Self-reported psychological
      wellbeing experiences of walking in urban settings were investigated with an
      innovative application of the photo-elicited interview. Fourteen adults took
      individual walks in Bristol city centre and photographed their journey;
      photographs were then discussed during the interview. Participants reported
      specific engagements with place related to personal connections, the identity of
      place, and sense of community that resulted in psychological wellbeing benefits.
      The findings also support the notion that non-natural elements can promote
      positive affective and cognitive appraisals. Building on the finding that also
      urban walking can support psychological wellbeing, the findings encourage future
      research into the health potential of different characteristics of built
      environments.

PMID- 30195154
TI  - Decontamination of select infrastructure materials after a radiological incident
      using a water-based formulation.
AB  - This paper summarizes the results of the decontamination of the infrastructure
      materials concrete, limestone, brick and asphalt contaminated with 60Co, 85Sr,
      137Cs and 241Am. The paper focuses on the effect of differences in substrate
      properties and of the pH of the radionuclide solution used for surface
      contamination on adsorption or ion exchange of the radionuclides and how these
      factors affect the decontamination effectiveness. A six-component chemical
      formulation was used and a process effectiveness of up to 76% was obtained
      depending on the substrate and radionuclide. Asphalt was the easiest material to
      decontaminate because of its more hydrophobic nature. Concrete and limestone (and
      to some extent brick) were less effectively decontaminated as their porous
      surfaces allowed penetration of radionuclides into water-filled pores in the
      substrate facilitating adsorption or ion exchange and making them difficult to
      remove. Brick was the most difficult material to decontaminate because the major
      component of brick is clay which retains most mono- and divalent ions. The
      removal of 60Co, 85Sr and 137Cs from the surfaces of concrete, limestone and
      brick increased when the pH of the radionuclide solutions was moderately acidic
      to neutral compared to when they were highly acidic. The variability in the test
      results was similar to that observed in other studies using other decontamination
      methods, attributed to the inhomogeneity of the substrates used and considered
      representative of real infrastructure materials.

PMID- 30195156
TI  - Interaction of nanoparticles with biological systems.
AB  - I feel very much honored that I was invited to contribute to a special issue for
      you, Heiri, in the prestigious Journal Colloids and Surfaces B: Biointerfaces.
      Moreover, it is with great pleasure that I add a few pages on the topic I was
      involved with during my active research time, i.e. on the interaction of
      nanoparticles with biological systems, for this special issue. The research topic
      continued somehow into the time of my retirement, but with a broader view of
      nanoparticles, with my engagement in the National Research Program 64 on
      "Opportunities and Risks of Nanomaterials" of the Swiss National Science
      Foundation. It was wonderful having you as a world expert on physical-chemical
      aspects of nanomaterials (powders) in the Steering Committee. Your competence in
      this field of research work as well as your engagement have always been highly
      appreciated.

PMID- 30195157
TI  - Interdigitation in spin-coated lipid layers in air.
AB  - In this study, we show that dry saturated phospholipid layers prepared by the
      spin-coating technique could present thinner regions associated to interdigitated
      phases under some conditions. The morphological characteristics of lipid layers
      of saturated phosphocholines, such as dilauroylphosphatidylcholine (DLPC),
      dimyristoylphosphatidylcholine (DMPC), dipalmitoylphosphatidylcholine (DPPC) and
      distearoylphosphatidylcholine (DSPC), have been measured by Atomic Force
      Microscopy and revealed that the presence of interdigitated regions is not
      induced by the same parameters that induce them in hydrated samples. To achieve
      these results the effect of the lipid hidrocabonated chain length, the presence
      of alcohol in the coating solution, the spinning velocity and the presence of
      cholesterol were tested. We showed that DPPC and DSPC bilayers, on the one side,
      can show structures with similar height than interdigitated regions observed in
      hydrated samples, while, on the other side, DLPC and DMPC tend to show no
      evidence of interdigitation. Results indicate that the presence of interdigitated
      areas is due to the presence of lateral tensions and, hence, that they can be
      eliminated by releasing these tensions by, for instance, the addition of
      cholesterol. These results demonstrate that interdigitation in lipid layers is a
      rather general phenomena and can be observed in lipid bilayers in dry conditions.

PMID- 30195158
TI  - Electrochemical biosensor based on Se-doped MWCNTs-graphene and Y-shaped DNA
      aided target-triggered amplification strategy.
AB  - A highly sensitive electrochemical biosensor for detection of platelet-derived
      growth factor-BB (PDGF-BB) is developed by using Se-doped multi-walled carbon
      nanotubes (MWCNTs)-graphene hybrids as electrode supporting substrate, hemin/G
      quadruplex as trace labels and Y-shaped DNA-aided target recycling as signal
      magnifier. The aptamer-containing hairpin probes were first immobilized on the
      electrode. When target PDGF-BB was added, the aptamer binded PDGF-BB to trigger
      catalytic assembly of two other hairpins to form many G-quadruplex Y-junction DNA
      structures, which released PDGF-BB to again bind the intact aptamer to initiate
      another assembly cycle. G-quadruplex/hemin complexes were produced when hemin was
      added to generate substantially amplified current output. The developed assay
      showed a linear range toward PDGF-BB from 0.1 pM to 10 nM with a detection limit
      of 27 fM (S/N = 3). The method showed excellent specificity and repeatability,
      and could be expediently applied for sensitive detection of other molecules by
      simply changing the aptamers.

PMID- 30195159
TI  - Disulfide-based PEGylated prodrugs: Reconversion kinetics, self-assembly and
      antitumor efficacy.
AB  - The prodrug strategy serves well in drug formulation and delivery. Two disulfide
      based PEGylated prodrugs were developed and the drug reconversion upon different
      conditions were studied in detail. The reconversion-induced oversaturation
      phenomenon was firstly reported here. We found the prodrug can co-assemble with
      parent drug via pi-pi stacking into well-defined nanoparticles. The PEG layer of
      the self-assembled nanoparticles improved the stability of the PEGylated prodrug
      by reducing the contact with biological enzymes. The nanoparticles also show
      favorable antitumor efficacy, both in vitro and in vivo.

PMID- 30195160
TI  - Major and minor elemental compositions of streambed biofilms and its implications
      of riverine biogeochemical cycles.
AB  - Chemical compositions of streambed biofilms from a major river of central Japan
      (the Kushida River) were obtained, with data of associated sediments (fine
      grained fractions < 63 MUm) and dissolved components of waters, in order to
      provide preliminary information about biogeochemical significance of streambed
      biofilms. During the sampling period (July 31st to August 3rd, 2013), dissolved
      components of the river waters were influenced by the dam reservoir.
      Concentrations of NO3-, silica (as Si), SO42-, PO43- and Ca2+ decreased across
      the dam, whereas Fe and Mn increased across the dam, and then decreased
      downstream rapidly. Streambed biofilms contain significant amount of non-nutrient
      elements such as Al (up to 21% as Al2O3 on water and others-free basis),
      indicating that they are contaminated as siliciclatic (silt and clay) materials.
      Siliciclastic materials in the biofilms are basically compositionally similar to
      fine-grained (<63 MUm) fractions of streambed sediments. However, some elements
      such as Ca, P, Mn, and Zn are markedly enriched in the biofilms. Particularly, Mn
      concentrations in the biofilm samples collected just below the dam reservoir are
      very high (~4.0 wt %), probably due to accumulation from the discharged water.
      Concentrations of trace elements such as P, Cr, Cu, Zn and V appear to be
      controlled by amounts of Fe-oxides and/or Mn-oxides in biofilms. Numbers of
      factors are involved in controlling chemical compositions of streambed biofilms,
      including amount of contaminated siliciclastics, authigenic mineral formation,
      adsorption of dissolved materials and microbial metabolisms. As demonstrated by
      this study, systematic analyses including major elements and comparison with
      associated sediments and waters could reveal biogeochemistry of this complex
      system.

PMID- 30195161
TI  - Urinary metabolites of organophosphate flame retardants in 0-5-year-old children:
      Potential exposure risk for inpatients and home-stay infants.
AB  - Organophosphate flame retardants (OPFRs) have been commonly observed in indoor
      dust, food, and drinking water in China, but little is known about their exposure
      levels or factors leading to exposure in Chinese children. In this study, we
      measured eight metabolites of OPFRs (mOPFRs) in 227 urine samples collected from
      0- to 5-year-old children in China. The high detection rates of mOPFRs (60%-100%)
      in the collected urine samples demonstrated the widespread exposure of this
      population to OPFRs. The median concentrations indicated that bis(2
      chloroethyl)phosphate (BCEP, 0.85 ng/mL) and diphenyl phosphate (DPHP, 0.27
      ng/mL) were the dominant chlorinated mOPFRs and nonchlorinated mOPFRs,
      respectively. Interestingly, the median urinary levels of bis(1-chloro-2
      propyl)phosphate (BCIPP, 6.48 ng/mL) and bis(2-butoxyethyl)phosphate (BBOEP, 0.31
      ng/mL) in inpatient infants were one order of magnitude higher (p < 0.01) than
      those observed in outpatient infants. For home-stay participants, furthermore,
      infants (0-1 year) had the highest median levels of BCIPP (0.72 ng/mL) and
      dibutyl phosphate (DBP, 0.14 ng/mL) among the three age groups (i.e., 0-1, >1-3,
      and >3-5 years), and significantly (p < 0.05) negative age-related relationships
      were found for both urinary mOPFRs. Two set of data on estimated daily intakes
      (EDIs) were calculated based on the fraction of OPFR excreted as the
      corresponding mOPFR (FUE) in human liver microsomes (EDIHLM) and S9 fraction
      (EDIS9) system, respectively. In general, children have relatively high EDIs of
      tris(2-chloroethyl)phosphate (TCEP: EDIHLM = 485 ng/kg bw/day, EDIS9 = 261 ng/kg
      bw/day). Furthermore, 17% or 21% of inpatient infants had EDIs that exceeded the
      reference dose, whereas this value was reduced to 13% in outpatient infants; and
      this value decreased with age among all home-stay children (0-5 years). Our
      results indicated that inpatient and home-stay infants had a higher potential
      risk of OPFR exposure. To our knowledge, this is the first study to identify the
      elevated urinary levels of mOPFRs in inpatients.

PMID- 30195162
TI  - Dynamic membrane bioreactor (DMBR) for the treatment of landfill leachate;
      bioreactor's performance and metagenomic insights into microbial community
      evolution.
AB  - The use of dynamic membranes as a low-cost alternative for conventional membrane
      for the treatment of landfill leachate (LFL) was investigated in this study. For
      this purpose a lab-scale, submerged pre-anoxic and post-aerobic bioreactor
      configuration was used with nylon mesh as dynamic membrane support. The study was
      conducted at ambient temperature and LFL was fed to the bioreactor in gradually
      increasing concentration mixed with tap water (from 20% to 100%). The results of
      this study demonstrated that lower mesh pore size of 52 MUm achieved better
      results in terms of solid-liquid separation performance (turbidity <10 NTU) of
      the formed dynamic membrane layer as compared to 200 and 85 MUm meshes while
      treating LFL. Consistently high NH4+-N conversion efficiency of more than 98% was
      achieved under all nitrogen loading conditions, showing effectiveness of the
      formed dynamic membrane in retaining slow growing nitrifying species. Total
      nitrogen removal reached more than 90% however, the denitrification activity
      showed a fluctuating profile and found to be inhibited by elevated concentrations
      of free nitrous acid and NO2--N at low pH values inside the anoxic bioreactor. A
      detailed metagenomic analysis allowed a taxonomic investigation over time and
      revealed the potential biochemical pathways involved in NH4+-N conversion. This
      study led to the identification of a dynamic system in which nitrite
      concentration is determined by the contribution of NH4+ oxidizers (Nitrosomonas),
      and by a competition between nitrite oxidizers (Nitrospira and Nitrobacter) and
      reducers (Thauera).

PMID- 30195163
TI  - Biomineralization of strontium and barium contributes to detoxification in the
      freshwater alga Micrasterias.
AB  - The unicellular model alga Micrasterias denticulata inhabits acid peat bogs that
      are highly endangered by pollutants due to their high humidity. As it was known
      from earlier studies that algae like Micrasterias are capable of storing barium
      naturally in form of BaSO4 crystals, it was interesting to experimentally
      investigate distribution and sequestration of barium and the chemically similar
      alkaline earth metal strontium. Additionally, we intended to analyze whether
      biomineralization by crystal formation contributes to diminution of the generally
      toxic effects of these minerals to physiology and structure of this alga which is
      closely related to higher plants. The results show that depending on the
      treatment differently shaped crystals are formed in BaCl2 and Cl2Sr exposed
      Micrasterias cells. Modern microscopic techniques such as analytical TEM by
      electron energy loss spectroscopy and Raman microscopy provide evidence for the
      chemical composition of these crystals. It is shown that barium treatment results
      in the formation of insoluble BaSO4 crystals that develop within distinct
      compartments. During strontium exposure long rod-like crystals are formed and are
      surrounded by membranes. Based on the Raman signature of these crystals their
      composition is attributed to strontium citrate. These crystals are instable and
      are dissolved during cell death. During strontium as well as barium treatment
      cell division rates and photosynthetic oxygen production decreased in dependence
      of the concentration, whereas cell vitality was reduced only slightly. Together
      with the fact that TEM analyses revealed only minor ultrastructural alterations
      as consequence of relatively high concentrated BaCl2 and Cl2Sr exposure, this
      indicates that biomineralization of Sr and Ba protects the cells from severe
      damage or cell death at least within a particular concentration range and time
      period. In the case of Sr treatment where ROS levels were found to be elevated,
      hallmarks for autophagy of single organelles were observed by TEM, indicating
      beginning degradation processes.

PMID- 30195164
TI  - Predicting hospital readmission for lupus patients: An RNN-LSTM-based deep
      learning methodology.
AB  - Hospital readmission is one of the critical metrics used for measuring the
      performance of hospitals. The HITECH Act imposes penalties when patients are
      readmitted to hospitals if they are diagnosed with one of the six conditions
      mentioned in the Act. However, patients diagnosed with lupus are the sixth
      highest in terms of rehospitalization. The heterogeneity in the disease and
      patient characteristics makes it very hard to predict rehospitalization. This
      research utilizes deep learning methods to predict rehospitalization within 30
      days by extracting the temporal relationships in the longitudinal EHR clinical
      data. Prediction results from deep learning methods such as LSTM are evaluated
      and compared with traditional classification methods such as penalized logistic
      regression and artificial neural networks. The simple recurrent neural network
      method and its variant, gated recurrent unit network, are also developed and
      validated to compare their performance against the proposed LSTM model. The
      results indicated that the deep learning method RNN-LSTM has a significantly
      better performance (with an AUC of .70) compared to traditional classification
      methods such as ANN (with an AUC of 0.66) and penalized logistic regression (with
      an AUC of 0.63). The rationale for the better performance of the deep learning
      method may be due to its ability to leverage the temporal relationships of the
      disease state in patients over time and to capture the progression of the disease
      relevant clinical information from patients' prior visits is carried forward in
      the memory, which may have enabled the higher predictability for the deep
      learning methods.

PMID- 30195165
TI  - Unusual subunits are directly involved in binding substrates for natural rubber
      biosynthesis in multiple plant species.
AB  - Rubber particles from rubber-producing plant species have many different species
      specific proteins bound to their external monolayer biomembranes. To date,
      identification of those proteins directly involved in enzymatic catalysis of
      rubber polymerization has not been fully accomplished using solubilization,
      purification or reconstitution approaches. In an alternative approach, we use
      several tritiated photoaffinity-labeled benzophenone analogs of the allylic
      pyrophosphate substrates, required by rubber transferase (RT-ase) to initiate the
      synthesis of new rubber molecules, to identify the proteins involved in
      catalysis. Enzymatically-active rubber particles were purified from three
      phylogenetically-distant rubber producing species, Parthenium argentatum Gray,
      Hevea brasiliensis Muell. Arg, and Ficus elastica Roxb., each representing a
      different Superorder of the Dicotyledonae. Geranyl pyrophosphate with the
      benzophenone in the para position (Bz-GPP(p)) was the most active initiator of
      rubber biosynthesis in all three species. When rubber particles were exposed to
      ultra-violet radiation, 95% of RT-ase activity was eliminated in the presence of
      50 MUMU Bz-GPP(p), compared to only 50% of activity in the absence of this
      analog. 3H-Bz-GPP(p) then was used to label and identify the proteins involved in
      substrate binding and these proteins were characterized electrophoretically. In
      all three species, three distinct proteins were labeled, one very large protein
      and two very small proteins, as follows: P. argentatum 287,000, 3,990, and 1,790
      Da; H. brasiliensis 241,000, 3,650 and 1,600 Da; F. elastica 360,000, 3,900 and
      1,800 Da. The isoelectric points of the P. argentatum proteins were 7.6 for the
      287,000 Da, 10.4 for the 3,990 Da and 3.5 for the 1,790 Da proteins, and of the
      F. elastica proteins were 7.7 for the 360,000 Da, 6,0 for the 3,900 Da, and 11.0
      for the 1,800 Da proteins. H. brasiliensis protein pI values were not determined.
      Additional analysis indicated that the three proteins are components of a
      membrane-bound complex and that the ratio of each small protein to the large one
      is 3:1, and the large protein exists as a dimer. Also, the large proteins are
      membrane bound whereas both small proteins are strongly associated with the large
      proteins, rather than to the rubber particle proteolipid membrane.

PMID- 30195166
TI  - Detection of the first higher plant epoxyalcohol synthase: Molecular cloning and
      characterisation of the CYP74M2 enzyme of spikemoss Selaginella moellendorffii.
AB  - The CYP74M2 gene of a model plant, the spikemoss Selaginella moellendorffii
      Hieron, was cloned and the catalytic properties of corresponding recombinant
      protein were studied. The recombinant CYP74M2 protein was active towards 13
      hydroperoxides of linoleic and a-linolenic acids (13-HPOD and 13-HPOT,
      respectively). In contrast to previously studied CYP74M1 and CYP74M3, which
      possessed the divinyl ether synthase activity, CYP74M2 behaved as a dedicated
      epoxyalcohol synthase (EAS). For instance, the 13-HPOD was converted to three
      epimeric oxiranyl carbinols 1-3 (formed at a ratio ca. 4:2:1), namely the
      (11R,12S,13S), (11R,12R, 13S), and (11S,12S,13S) epimers of (9Z)-11-hydroxy-12,13
      epoxy-9-octadecenoic acid. Besides these products, a minority of oxiranyl vinyl
      carbinols like (10E)-11-hydroxy-12,13-epoxy-9-octadecenoic acid was formed. The
      13-HPOT conversion by CYP74M2 afforded two stereoisomers of 11-hydroxy-12,13
      epoxy-9,15-octadecadienoic acid. Individual oxylipins were purified by HPLC and
      finally identified by their NMR data, including the 1H-NMR, 2D-COSY, HSQC, and
      HMBC. Thus, the CYP74M2 is the dedicated epoxyalcohol synthase. To our knowledge,
      no enzymes of this type have been detected in higher plants yet.

PMID- 30195167
TI  - Molecularly imprinted solid phase extraction coupled with gas chromatography-mass
      spectrometry for determination of N-Nitrosodiphenylamine in water samples.
AB  - In this study, the molecularly imprinted polymers (MIPs) with high specific
      surface area and extraction efficiency of N-Nitrosodiphenylamine (NDPhA) were
      successfully prepared and a highly sensitive and selective method was developed
      for determination of NDPhA in water samples using MIPs solid-phase extraction
      (SPE) coupled with gas chromatography mass spectrometry (GC-MS) detection. The
      MIPs were successfully prepared using the method of precipitation polymerization
      and using methacrylic acid as the functional monomer, ethylene glycol
      dimethacrylate as the cross-linker, and N, N-Diphenylformamide as the template
      molecule. The newly synthesized MIPs were characterized and used as SPE sorbents.
      Under the optimized conditions, the average recoveries of NDPhA spiked in
      ultrapure water were higher than 94% +/- 2.9% at three different concentrations
      and the limit of detection and limit of quantitation were 0.8 ng L-1 and 2.4 ng L
      1, respectively. Moreover, the high selectivity of MIPs was attained and the
      satisfactory recoveries of NDPhA which were spiked in to real samples were
      achieved in the range of 92-107% with relative standard deviations (RSDs) within
      0.3-7.9%. The low levels of NDPhA were detected in the two of twelve wastewater
      samples with concentrations of 5.6 ng L-1 and 3.6 ng L-1 with RSDs of 5.6% and
      2.8%, respectively. The developed MIP-SPE method was proved to be practically
      feasible for selective extraction and enrichment of NDPhA in real water samples.

PMID- 30195168
TI  - Color and nitrogen removal from synthetic dye wastewater in an integrated
      mesophilic hydrolysis/acidification and multiple anoxic/aerobic process.
AB  - Dye wastewater is one kind of refractory pollutant and it is commonly treated by
      the integrated anaerobic and aerobic process. A new integrated
      hydrolysis/acidification and multiple anoxic/aerobic (AO) process was proposed
      for the removal of color and nitrogen from azo dye wastewater. System
      performance, the degradation pathway of azo dye and nitrogen metabolic pathway
      were investigated with quadrupole-time-of-flight and metagenomic analyses. The
      proposed process removed color and nitrogen efficiently, with the removal
      percentages of 89.4% and 54.0%, respectively. A colorful intermediate
      C16H11N3O7S2 during the degradation of azo dye was detected. Controlling a low
      dissolved oxygen concentration in the multiple AO process could enhance nitrogen
      removal. The detected bacteria possessing azoreductase for the azo dye
      degradation included Desulfovibrio aminophilus, Thermoanaerobacter, Lactococcus
      raffinolactis, Ruminiclostridium and Rhodopirellula. The nitrifying genes of amo
      and hao were mainly detected in Nitrosomonas, while the denitrifying genes were
      detected in Thauera, Candidatus Accumulibacter and Rhodothermus marinus.

PMID- 30195170
TI  - Modelling stroking parameters in competitive sprint swimming: Understanding inter
      and intra-lap variability to assess pacing management.
AB  - This study investigated the inter- and intra-lap variability in stroking
      parameters during sprint competition to gain insight into the race management of
      speed (S), stroke length (SL), stroke rate (SR) and stroke index (SI) in relation
      to gender. The stroking parameters of 32 male and 32 female finalists in the 2015
      World Championships and French Championships were analysed during 50-m and 100-m
      freestyle events. Using a video-derived two-dimensional direct linear
      transformation system, the biological coefficients of variation (BCV) between
      cycles were computed for the 50-m and the two laps of the 100-m (L1100, L2100).
      Speed changes within each lap were modelled by linear, quadratic or cubic models.
      The 50-m showed higher S and SR but lower SL and SI than L1100. The 50-m
      exhibited greater BCV S than L1100, which showed higher S, SR, SL and SI than
      L2100. BCV S and BCV SL were lower in L1100 than L2100 but BCV SR was higher in
      L1100 than L2100. Male swimmers showed greater BCV S than female swimmers in the
      50-m and L1100. For the whole population, the linear regression model was
      dominant in the 50-m (53.1%), L1100 (53.1%) and L2100 (43.8%). High mean speed
      often related to high intra-lap speed fluctuations and a linear speed decrease in
      the 50-m suggesting an 'all-out' pacing, while lower fluctuations occurred during
      the 100-m suggesting an 'economical' pacing.

PMID- 30195171
TI  - Metabolomics in chronic kidney disease: Strategies for extended metabolome
      coverage.
AB  - Chronic kidney disease (CKD) is becoming a major public health issue as
      prevalence is increasing worldwide. It also represents a major challenge for the
      identification of new early biomarkers, understanding of biochemical mechanisms,
      patient monitoring and prognosis. Each metabolite contained in a biofluid or
      tissue may play a role as a signal or as a driver in the development or
      progression of the pathology. Therefore, metabolomics is a highly valuable
      approach in this clinical context. It aims to provide a representative picture of
      a biological system, making exhaustive metabolite coverage crucial. Two aspects
      can be considered: analytical and biological coverage. From an analytical point
      of view, monitoring all metabolites within one run is currently impossible.
      Multiple analytical techniques providing orthogonal information should be carried
      out in parallel for coverage improvement. The biological aspect of metabolome
      coverage can be enhanced by using multiple biofluids or tissues for in-depth
      biological investigation, as the analysis of a single sample type is generally
      insufficient for whole organism extrapolation. Hence, recording of signals from
      multiple sample types and different analytical platforms generates massive and
      complex datasets so that chemometric tools, including data fusion approaches and
      multi-block analysis, are key tools for extracting biological information and for
      discovery of relevant biomarkers. This review presents the recent developments in
      the field of metabolomic analysis, from sampling and analytical strategies to
      chemometric tools, dedicated to the generation and handling of multiple
      complementary metabolomic datasets enabling extended metabolite coverage to
      improve our biological knowledge of CKD.

PMID- 30195169
TI  - Unraveling the ecotoxicity of deep eutectic solvents using the mixture toxicity
      theory.
AB  - The interest on deep eutectic solvents (DES) has been increasing. However, the
      ecotoxicological profile of DES is scarcely known. Also, despite previous studies
      showed that DES components dissociate in water, none assessed DES toxicity using
      the classical and adequate models for mixture toxicity prediction - concentration
      addition (CA) and independent action (IA). This study evaluates the
      ecotoxicological profile of DES based on [N1111]Cl, [N2222]Cl and [N3333]Cl as
      hydrogen bond acceptors (HBA) combined with hydrogen-bond donors (HBD) vis.
      ethylene glycol and 1-propanol, through the Microtox(r) Acute Toxicity Test. CA
      and IA with deviations describing synergism/antagonism, dose-ratio and dose-level
      effects were fitted to the toxicity data. Neither the starting materials nor DES
      were found hazardous to Aliivibrio fischeri, in this specific case agreeing with
      the claimed "green character" of DES. Among the starting materials, ethylene
      glycol was the least toxic, whereas [N3333]Cl was the most toxic (30 min-EC50 =
      96.49 g L-1 and 0.5456 g L-1, respectively). DES toxicity followed the same trend
      as observed for the salts: [N1111]Cl-based DES < [N2222]Cl-based DES < [N3333]Cl
      based DES. The IA model, with specific deviations, adjusted better in 5 out of 6
      DES. Antagonism was observed for [N1111]Cl-based DES, and synergism for [N3333]Cl
      based DES and for 1-propanol:[N2222]Cl. The application of the mixture toxicity
      models represents a breakthrough in the problematic of assessing the toxicity of
      the countless number of DES that can be created with the same starting materials,
      since they provide the expected toxicity of any virtual combination between HBA
      and HBD.

PMID- 30195172
TI  - Testosterone is related to GABA+ levels in the posterior-cingulate in unmedicated
      depressed women during reproductive life.
AB  - BACKGROUND: The role of testosterone (T) in the pathophysiology of affective
      disorders and anxiety is broadly supported. Evidence suggests that T has
      anxiolytic and antidepressant properties. One proposed route for the central
      effects of T is its interaction with the gamma-aminobutyric acid (GABA) system.
      We explored the relationship between T levels and GABA+ levels in anterior
      cingulate (ACC) and the posterior-cingulate (PCC) regions in depressed women,
      using magnetic resonance spectroscopy (1H-MRS). METHODS: Twenty-one depressed
      patients with regularly cycling who were not taking hormonal or psychotropic
      drugs were recruited. We assessed severity of depression using the Hamilton
      Depression Rating Scale (HDRS). Blood samples were taken for quantification of
      free (FT) and total testosterone (TT) on the day of the magnetic resonance (MR)
      scan. We evaluated GABA+ levels in the PCC and ACC, using the Hadamard Encoding
      and Reconstruction of MEGA-Edited Spectroscopy (HERMES) sequence. Pearson
      correlations were used to evaluate the association between FT, TT, GABA+
      concentrations, and HDRS scores. RESULTS: TT and FT levels were positively
      correlated with GABA+ levels in the PCC. No correlation was observed between T
      levels and GABA+ levels in the ACC. The HDRS total scores correlated negatively
      with FT levels. LIMITATIONS: Limitations include the cross-sectional evaluation
      and the lack of a comparative healthy group. CONCLUSIONS: Our findings suggest
      that the potential anxiolytic and antidepressant properties of T are related to
      increased GABA+ levels in the PCC. This observation may contribute to increased
      understanding of the role of T in depressive and anxiety symptoms in women.

PMID- 30195173
TI  - The burden of treatment-resistant depression: A systematic review of the economic
      and quality of life literature.
AB  - BACKGROUND: Major depressive disorder (MDD) is a global public health concern. In
      particular, treatment-resistant depression (TRD) represents a key unmet need in
      the management of MDD. A systematic review of the epidemiological and economic
      literature on the burden associated with an increasing number of treatment steps
      due to TRD/non-response within an MDD episode was performed to quantify the
      burden of TRD. METHODS: Studies were identified in the PubMed/Medline databases
      through April 27th, 2017. Articles were limited to full-length peer-reviewed
      journal publications with no date restrictions. Economic and patient health
      related quality of life (HRQoL) data on non-response by the number of treatment
      steps were quantified and, where appropriate, compared across studies; otherwise,
      comparative data within studies were reported. RESULTS: The 12 studies on
      economic burden found an association between increasing levels of TRD/non
      response and elevations in direct and indirect costs. Likewise, the 19 studies
      studying HRQoL burden found that increasing levels of TRD/non-response correlated
      with reduced patient HRQoL and health status. LIMITATIONS: TRD is defined
      inconsistently, which results in notable heterogeneity between published studies
      and poses methodological challenges for between-study comparisons. It is unknown
      if the increased economic and patient HRQoL burden are due to factors associated
      with TRD/non-response in addition to those due to depression persistence or
      severity. CONCLUSIONS: A consistent trend was observed such that medical costs
      increased and patient HRQoL and health status decreased by increasing level of
      TRD/non-response within an MDD episode. These findings highlight the need for
      improved therapies for TRD to help reduce disease burden.

PMID- 30195174
TI  - Habenular connectivity may predict treatment response in depressed psychiatric
      inpatients.
AB  - INTRODUCTION: The habenula (Hb) is a small midbrain structure that signals
      negative events and may play a major role in the etiology of psychiatric
      disorders including depression. The lateral Hb has three major efferent
      connections: serotonergic raphe nuclei, noradrenergic locus coeruleus, and
      dopaminergic ventral tegmental area/substantia nigra compacta. We wanted to test
      whether Hb connectivity may be important to predict treatment outcomes in
      depression patients. METHODS: We studied whether habenular connectivity at
      admission into a psychiatric clinic can predict treatment response. We used an
      inpatient sample (N = 175) to assess habenular connectivity (diffusion tensor
      imaging and resting state functional connectivity (RSFC) between the Hb and its
      targets) close to admission. In addition, we obtained the Patient Health
      Questionnaire-depression module (PHQ-9) close to admission and at discharge.
      Inpatients in the study entered the clinic with at least moderately severe
      depression (score 15 and up). Inpatients considered treatment resistant had
      scores of 9 or more at discharge. RESULTS: Compared to responders, treatment non
      responders had lower fractional anisotropy in the right Hb afferent fibers and
      lower RSFC between right Hb and median raphe, but higher RSFC between left Hb and
      locus coeruleus. A logistic regression model was significantly different from
      chance, and explained 27.7% of the variance in treatment resistance (sensitivity
      = 75%; specificity = 71.9%). DISCUSSION: The anatomical and functional
      connectivity of the Hb may be a predictor of treatment success in psychiatric
      populations. Limitations include the Hb small size and the limited time (5 min)
      of resting state data obtained.

PMID- 30195175
TI  - Prenatal exposure to phthalates and phenols and infant endocrine-sensitive
      outcomes: The MIREC study.
AB  - BACKGROUND: Anogenital distance (AGD) and the second to fourth finger (2D:4D)
      digit ratio may be early markers of in utero androgen exposure for the infant.
      Phthalates and phenols have been identified as endocrine disrupting chemicals.
      OBJECTIVES: To study the association between prenatal exposure to phthalates,
      bisphenol A (BPA) and triclosan (TCS) and AGD and the 2D:4D digit ratios.
      METHODS: Single spot urine samples were collected in the first trimester from the
      MIREC Study and analyzed for phthalates and phenols. Anogenital distance (n =
      394) at birth and 2D:4D digit ratios (n = 420) at 6 months were measured in male
      and female infants. Associations between maternal concentrations of phenols and
      phthalate metabolites and these outcomes were estimated using multiple linear
      regression models. RESULTS: In females, the anoclitoris distance (ACD) was
      negatively associated with mono-benzyl phthalate (MBzP) (beta = -1.24; 95% CI 
      1.91, -0.57) and positively associated with mono-ethyl phthalate (MEP) (beta =
      0.65; 95% CI 0.12, 1.18) (masculinizing). In males, anopenile distance (APD) was
      positively associated with mono-n-butyl phthalate (MnBP) (beta = 1.17; 95% CI
      0.02, 2.32) and the molar sum of low molecular weight phthalates (SigmaLMW).
      Female 2D:4D of the right hand was positively associated with MnBP and negatively
      with total BPA (masculinizing). CONCLUSIONS: Significant associations were only
      observed for the long AGD metrics. Positive associations were observed between
      MnBP or LMW phthalates and APD in males. In females, prenatal MEP was associated
      with a masculinizing effect on ACD, while MBzP was associated with a feminizing
      effect. No significant associations were observed between prenatal phenols and
      AGD. Given the paucity of research on digit ratios and prenatal chemical
      exposures, it is difficult to say whether this metric will be a useful marker of
      prenatal androgen or anti-androgen exposure. Given the large number of
      associations examined, the statistical associations observed may have been due to
      Type 1 error. The inconsistencies in results between studies suggest that this
      issue is yet to be resolved.

PMID- 30195176
TI  - Oxytocin is involved in steroid hormone-stimulated bovine satellite cell
      proliferation and differentiation in vitro.
AB  - Sex steroid hormones are used in the meat industry due to their ability to
      regulate muscle hypertrophy. However, the mechanisms underlying their action are
      not fully elucidated. Recent reports demonstrate that steroid hormones increase
      oxytocin (OXT) expression in skeletal muscle, indicating that OXT may play a role
      in satellite cell activity. This hypothesis was tested using steroid hormones
      (17beta-estradiol [E2]; trenbolone acetate [TBA]), tamoxifen (TAM), OXT, and
      atosiban (A: OXT receptor inhibitor) applied to bovine satellite cells (BSCs) to
      investigate BSC regulation by OXT. Oxytocin alone increased fusion index (P <
      0.05) but not BSC proliferation. Oxytocin reduced (P < 0.05) apoptotic nuclei and
      stimulated migration rate (P < 0.05). Similarly, E2 and TBA increased (P < 0.05)
      BSC proliferation rate, fusion index, and migration and decreased (P < 0.05)
      apoptotic nuclei. 17beta-Estradiol or TBA supplemented with A had lower (P <
      0.05) BSC proliferation rate, fusion index, and migration and more (P < 0.05)
      apoptotic nuclei compared with E2 or TBA alone. Furthermore, OXT expression
      increased (P < 0.05) in E2 or TBA-treated proliferating BSC. Oxytocin, E2, and
      TBA increased (P < 0.05) MyoD and MyoG expression in proliferating BSC. During
      BSC differentiation, OXT expression increased (P < 0.05) with E2 or TBA
      treatments. MyoG expression increased (P < 0.05) in OXT, E2, and TBA compared
      with control. However, A, OXT + A, TAM, TAM + OXT, E2 + TAM, E2 + A, and TBA + A
      decreased (P < 0.05) MyoG expression during BSC differentiation. These results
      indicate that OXT is involved in steroid hormone-stimulated BSC activity.

PMID- 30195177
TI  - Inversion produces opposite size illusions for faces and bodies.
AB  - Faces are complex, multidimensional, and meaningful visual stimuli. Recently,
      Araragi, Aotani, & Kitaoka (2012) demonstrated an intriguing face size illusion
      whereby an inverted face is perceived as larger than a physically identical
      upright face. Like the face, the human body is a highly familiar and important
      stimulus in our lives. Here, we investigated the specificity of the size
      underestimation of upright faces illusion, testing whether similar effects also
      hold for bodies, hands, and everyday objects. Experiments 1a and 1b replicated
      the face-size illusion. No size illusion was observed for hands or objects.
      Unexpectedly, a reverse size illusion was observed for bodies, so that upright
      bodies were perceived as larger than their inverted counterparts. Experiment 2
      showed that the face illusion was maintained even when the photographic contrast
      polarity of the stimuli was reversed, indicating that the visual system driving
      the illusion relies on geometric featural information rather than image contrast.
      In Experiment 2, the reverse size illusion for bodies failed to reach
      significance. Our findings show that size illusions caused by inversion show a
      high level of category specificity, with opposite illusions for faces and bodies.

PMID- 30195178
TI  - Brief aerobic exercise immediately enhances visual attentional control and
      perceptual speed. Testing the mediating role of feelings of energy.
AB  - While the effects of acute exercise on mood and cognitive functions have been
      separately documented over the last decade, recent findings have pointed to a
      possible connection between affective responses to exercise and cognitive
      performance. The main objective of this study was to test whether the effects of
      acute exercise on cognition were mediated by changes in feelings of energy. One
      hundred-and-one undergraduate students were randomized into one of two
      experimental conditions: 15 min of jogging at "moderate" intensity, or 15 min of
      relaxation/concentration (control condition). Perceptual speed, visual
      attentional control, working memory, and cognitive flexibility were assessed pre-
      and post-intervention in both groups via the Trail Making Test. Self-rated
      feelings of energy were also recorded pre- and post-intervention. Only completion
      time for the TMT-A significantly improved from pre- to post-intervention in
      participants who exercised compared with participants who practiced
      relaxation/concentration. No Group * Time interaction was found with regard to
      the other TMT variables. Finally, changes in feelings of energy were found to
      fully mediate the relationship between exercise and perceptual speed/visual
      attentional control. Taken together, our data suggest that a brief bout of
      moderate intensity exercise can improve the efficiency of certain cognitive
      processes through increases in feelings of energy, but further research is
      required to evaluate the duration of benefits and to determine whether these
      apply to other populations.

PMID- 30195179
TI  - The development of holistic face processing: An evaluation with the complete
      design of the composite task.
AB  - The composite paradigm is widely used to quantify holistic processing (HP) of
      faces: participants perform a sequential same-different task on one half (e.g.,
      top) of a test-face relative to the corresponding half of a study-face. There is,
      however, debate regarding the appropriate design in this task. In the partial
      design, the irrelevant halves (e.g., bottom) of test- and study-faces are always
      different; an alignment effect indexes HP. In the complete design, besides
      alignment, congruency between the irrelevant and critical halves of the test-face
      is manipulated regarding the same/different response status of the study-face.
      The HP indexed in the complete design does not confound congruency and alignment
      and has good construct and convergent validities. De Heering, Houthuys, & Rossion
      (2007) argued that HP is mature as early as 4-year-olds but employed the partial
      design. Here we revisit this claim, testing four groups of 4- to 9/10 year-old
      children and two groups of adults. We found evidence of HP only from 6-year-olds
      on when considering the complete design, whereas significant alignment effects
      were found in the index adopted in the partial design already in 4-year-olds but
      which we demonstrate that reflects other factors besides HP, including response
      bias associated with congruency.

PMID- 30195180
TI  - Semiempirical study on the absorption spectra of the coronene-like molecular
      models of graphene quantum dots.
AB  - Polycyclic aromatic hydrocarbons of the general formula C6n2H6n (coronene family)
      were used as molecular models of graphene quantum dots (GQDs). Absorption spectra
      of the model compounds were calculated by ZINDO/S method. The S0 -> S1 transition
      energy (E1) was found to decrease with n as E1 = 4.75 * n-0.633 eV. This
      transition is forbidden in symmetric compounds but 'switches on' upon symmetry
      breaking. The energy of the first bright optical peak (Ebr) was found to decrease
      with n as Ebr = 6.31 * n-0.6 eV. The data obtained corroborate the earlier
      finding that the size-independent optical properties of GQDs are determined by
      relatively small isolated sp2 clusters separated by sp3 (oxygen-contained)
      'defects' rather than the whole (corrupted) graphene sheets; such nanoparticles
      actually are not quantum dots. GQDs of pure (without defects) graphene sheets
      with fully pi-conjugated sp2 systems should exhibit size-dependent optical
      properties due to the quantum confinement effect.

PMID- 30195181
TI  - A coumarin based highly sensitive fluorescent chemosensor for selective detection
      of zinc ion.
AB  - A very effective and highly sensitive fluorescent chemosensor, based on 4
      hydroxycoumarin skeleton substituted by benzothiazole moiety was synthesized and
      investigated for the detection of zinc ion. This chemosensor displays highly
      selective and sensitive fluorescence enhancement to Zn2+ over other metal ions
      examined in solution and in biological systems. The detection limit for the
      fluorescent chemosensor 1 toward Zn2+ was 3.58 * 10-8 M. A simple and efficient
      approach was improved for the synthesis of chemosensor 1 starting from 4
      hydroxycoumarin.

PMID- 30195182
TI  - Highly efficient infrared to visible up-conversion emission tuning from red to
      white in Eu/Yb co-doped NaYF4 phosphor.
AB  - Eu/Yb co-doped NaYF4 phosphors have been synthesized by the combustion method.
      The Eu doping was fixed and the effect of Yb doping concentration on the
      structural, morphological and luminescence properties has been investigated. X
      ray diffraction analysis revealed that the phosphors consisted of mixed alpha-
      and beta-phases, but the beta-phase was dominant. All elements of the host and
      dopants, as well as adventitious C, were detected using X-ray photoelectron
      spectroscopy. The surface morphology showed a microrod-like structure with sharp
      hexagonal edges. Energy dispersive X-ray spectroscopy spectra proved the
      formation of the desired materials. The photoluminescence spectra illustrated the
      optical emission properties of Eu3+ in the red region when excited at 394 nm,
      while, under the same excitation, Yb3+ ions gave emission at 980 nm. The up
      conversion (UC) emission of Eu/Yb co-doped NaYF4 produced a white color at the
      higher concentration of Yb excited by a 980 nm laser, which was made possible by
      green emission of Er contamination (from Yb source) and blue emission of Eu2+
      ions. The lifetime of the Eu3+ UC luminescence at 615 nm was also affected by the
      Yb doping concentration. The temperature sensitivity associated with the Er3+
      peaks at 520 and 542 nm was assessed as a function of temperature and the maximum
      of 0.0040 K-1 occurred at 463 K.

PMID- 30195183
TI  - A high performance 2-hydroxynaphthalene Schiff base fluorescent chemosensor for
      Al3+ and its applications in imaging of living cells and zebrafish in vivo.
AB  - Developing high performance fluorescent chemo-sensors for in vitro and in vivo
      Al3+ detection is highly desirable, because Al3+ accumulation has been involved
      to various diseases. Herein, we report a highly selective and sensitive Schiff
      base fluorescent probe, H3L, based on 2-hydroxynaphthalene, which can recognize
      aluminum ions and exhibit an "off-on" mode with high selectivity in methanol
      solutions. The detection limit of the probe for Al3+ is as low as 10-7 M which
      was determined by fluorescent titration. The high selectivity and high
      sensitivity of H3L for Al3+ are attributed to the inhibition of ESIPT.
      Additionally, the distribution of intracellular Al3+ ions could be observed under
      confocal fluorescence microscopy. Moreover, we also applied H3L for in vivo
      detection of Al3+ ions in living zebrafish larvae.

PMID- 30195184
TI  - Proximity ligation assay induced and DNAzyme powered DNA motor for fluorescent
      detection of thrombin.
AB  - A novel DNA motor for thrombin detection was described here based on proximity
      ligation assay (PLA) induced DNAzyme recycling cleavage. Fluorophore labeled DNA
      is modified on gold nanoparticles (AuNPs) and the fluorescent signal is quenched
      by AuNPs. The PLA between target thrombin and two aptamers induces the forming of
      Mg2+-dependent DNAzyme. The fluorophore labeled DNA is cleaved circularly by the
      DNAzyme, releasing the fluorescent fragment from AuNPs surface. The cleavage and
      rebinding process create a processive walking along AuNPs surface track. As a
      result, the fluorescent intensity recovers significantly. A good linear
      relationship is obtained between the ratio of fluorescence intensity and thrombin
      concentration in the range from 10 pM to 10 nM. The limit of detection is
      calculated to be 4 pM. These results are comparable or even better than other
      amplification based methods.

PMID- 30195185
TI  - Powder carbonization to synthesize novel carbon dots derived from uric acid for
      the detection of Ag(I) and glutathione.
AB  - This article first reported that a simple synthesis of carbon dots (UCDs) by
      pyrolysis of uric acid was proposed. The excitation wavelength was 350 nm and the
      emission wavelength was 402 nm for the synthesized UCDs. And the corresponding
      fluorescence quantum yield was 52.06%. The obtained UCDs could be served as a
      fluorescence probe to recognize Ag+ and glutathione (GSH), respectively. The
      fluorescence of UCDs was quenched after the addition of Ag+. The obtained UCDs
      had a linear relationship with Ag+ in the detection range of 0.1 MUM to 2.0 MUM,
      and the detection limit was 39 nM. The quenching fluorescence of this system
      could be restored after adding GSH. The fluorescence intensity increased linearly
      on increasing the concentration of glutathione in the range of 4 to 9 MUM, and
      the detection limit was 66 nM. Based upon these phenomena, we proposed a novel
      fluorescence probe to detect Ag+ and detect GSH, respectively. In addition, the
      prepared UCDs were successfully applied to analyze Ag+ in mineral waters and GSH
      in blood serums.

PMID- 30195186
TI  - A new fluorene derived Schiff-base as a dual selective fluorescent probe for Cu2+
      and CN.
AB  - A new fluorene based fluorogenic chemosensor, 2-[(9H-Fluoren-2-ylmethylene)
      amino]-phenol (L), has been designed, synthesized, and characterized by CHN
      analyses and different spectroscopic methods. This turn-on fluorogenic
      chemosensor shows high selectivity and sensitivity toward Cu2+ and CN- with low
      detection limits of 1.54 * 10-9 M and 1.83 * 10-7 M, respectively. The
      stoichiometry ratio of L-Cu2+ in solution is 1:1, by the method of Job's plot and
      ESI-MS. The microcrystalline solid product of the chemosensor reaction with
      copper is characterized as CuL2. The chiT value for CuL2 is temperature
      independent at a value of 0.403 cm3 K mol-1, which is in agreement with a
      mononuclear copper(II) complex with an isotropic g-value of 2.075. The
      fluorescence turn-on recognition process for detection of Cu2+ is attributed to
      the restricted imine isomerization and blocking of intramolecular charge transfer
      (ICT) quenching process in the analyte-bound sensor. The selectivity of L for
      Cu2+ is based on the chelation-enhanced fluorescence effect (CHEF) mechanism.
      Other interfering ions such as Na+, K+, Ca2+, Mg2+, Ag+, Fe2+, Fe3+, Co2+, Ni2+,
      Zn2+, Cd2+, Hg2+, Mn2+, Pb2+ and Al3+, show no change in the fluorescence
      intensity of L in the presence of Cu2+. Furthermore, the compound L can be used
      as a fluorescence and colorimetric sensor for selective detection of CN- over a
      number of other anions based on the nucleophilic addition to the imine CN bond,
      with consequent hydrogen bond formation and electrostatic interaction of the
      resulting product with K+. The sensing mechanism for CN- was theoretically
      supported by DFT calculations.

PMID- 30195187
TI  - Theoretical insights into excited-state intramolecular and multiple
      intermolecular hydrogen bonds in 2-(2-Hydroxy-phenyl)-4(3H)-quinazolinone.
AB  - The photophysical properties and photochemistry reactions of 2-(2-Hydroxy-phenyl)
      4(3H)-quinazolinone (HPQ) system in different solutions are studied by using
      density functional theory (DFT) and time-dependent density functional theory
      (TDDFT) methods. Our theoretical investigation explores that an ultrafast barrier
      free excited state intramolecular proton transfer (ESIPT) process occurs and the
      configuration twisting is found in the electronic excited state. In the polar
      protic methanol solution, the hydrogen-bonded complex composed by HPQ and two
      methanol molecules (HPQ-2M) could exist stably in the ground state. Upon
      photoexcitation the isolated HPQ is initially excited to the first excited state,
      while the HPQ-2M system is firstly excited to the S3 state and undergoes internal
      conversion (IC) to the S1 state. The intermolecular hydrogen bonds are
      strengthened in the excited state. The simulated electronic spectra agree well
      with the experimental results. The strengthening of the intermolecular hydrogen
      bonds is also confirmed by the calculated vibrational spectra. In addition, the
      intramolecular charge transfer happens in both HPQ and HPQ-2M systems from the
      frontier molecular orbital analysis.

PMID- 30195188
TI  - Engineering mammalian cells for disease diagnosis and treatment.
AB  - Synthetic biology aims to repurpose cells to sense a wide range of input signals
      and respond by conditionally expressing user-defined output genes. In this
      review, we highlight the latest developments in synthetic-biology-inspired in
      vitro and in vivo diagnostics and therapeutics employing engineered mammalian
      cells. Recent work has led to the creation of modular synthetic receptors with
      adaptable ligand-binding domains whose recognition specificity can be easily
      tailored to target various diseases. Engineered cells can now sense a great
      variety of soluble and surface-bound antigens with unprecedented selectivity and
      sensitivity, and implanted designer cells equipped with appropriate response
      modules can successfully treat diabetes, cancer and autoimmune diseases in animal
      models. Recently, the first immunotherapies using chimeric-antigen receptor (CAR)
      T cells were approved to treat lymphoma patients. As this milestone paves the way
      for translating state-of-the-art synthetic biology approaches into clinical
      benefit, we also discuss the challenges facing engineered cell therapies.

PMID- 30195189
TI  - Motivators, barriers and strategies of weight management: A cross-sectional study
      among Finnish adults.
AB  - BACKGROUND: Weight management (WM) is an ongoing global challenge. The purpose of
      this study was to analyze motivators, barriers, and strategies of WM among
      Finnish adults. METHODS: Data were collected in the 'KULUMA' (Consumers at the
      Weight Management Market) project among 667 community-dwelling adults in Eastern
      and Central Finland (Kuopio and Jyvaskyla). The self-reported questionnaire
      collected background information and responses to motivators, barriers, and
      strategy items. Principal component analysis (PCA) was used to extract components
      of motivators, barriers, and strategies of WM, along with K-means clustering to
      categorize the participants. RESULTS: About 55% of the respondents were aiming to
      lose weight. The PCA resulted in a 3-component model for motivators (functional
      aspects, sociological aspects, and psychosocial aspects), a 4-component model for
      barriers (life situations, food environment, personal issues, and resources) and
      a 2-component model for the strategies of WM (dietary strategies and life
      management strategies). The components had several relationships with demographic
      characteristics (especially with age) but only a few with weight-related
      characteristics (e.g. weight loss attempts). Three clusters of participants were
      formed: Struggling weight managers (WMs), Independent WMs, and Determined WMs.
      Barriers to WM had a key role in differentiating clusters and weight
      satisfaction. Determined WMs were the most satisfied with their weight, whereas
      Struggling WMs perceived the highest level of barriers to WM. CONCLUSIONS: WM
      efforts are common among Finnish adults. Generally, weight-related activities and
      communication in society should focus more on barriers than merely on the
      motivation or strategies of WM in order to support individuals' WM efforts.

PMID- 30195190
TI  - A distinct class of antioxidant response elements is consistently activated in
      tumors with NRF2 mutations.
AB  - NRF2 is a redox-responsive transcription factor that regulates expression of
      cytoprotective genes via its interaction with DNA sequences known as antioxidant
      response elements (AREs). NRF2 activity is induced by oxidative stress, but
      oxidative stress is not the only context in which NRF2 can be activated.
      Mutations that disrupt the interaction between NRF2 and KEAP1, an inhibitor of
      NRF2, lead to NRF2 hyperactivation and promote oncogenesis. The mechanisms
      underlying NRF2's oncogenic properties remain unclear, but likely involve
      aberrant expression of select NRF2 target genes. We tested this possibility using
      an integrative genomics approach to get a precise view of the direct NRF2 target
      genes dysregulated in tumors with NRF2 hyperactivating mutations. This approach
      revealed a core set of 32 direct NRF2 targets that are consistently upregulated
      in NRF2 hyperactivated tumors. This set of NRF2 "cancer target genes" includes
      canonical redox-related NRF2 targets, as well as target genes that have not been
      previously linked to NRF2 activation. Importantly, NRF2-driven upregulation of
      this gene set is largely independent of the organ system where the tumor
      developed. One key distinguishing feature of these NRF2 cancer target genes is
      that they are regulated by high affinity AREs that fall within genomic regions
      possessing a ubiquitously permissive chromatin signature. This implies that these
      NRF2 cancer target genes are responsive to oncogenic NRF2 in most tissues because
      they lack the regulatory constraints that restrict expression of most other NRF2
      target genes. This NRF2 cancer target gene set also serves as a reliable proxy
      for NRF2 activity, and high NRF2 activity is associated with significant
      decreases in survival in multiple cancer types. Overall, the pervasive
      upregulation of these NRF2 cancer targets across multiple cancers, and their
      association with negative outcomes, suggests that these will be central to
      dissecting the functional implications of NRF2 hyperactivation in several cancer
      contexts.

PMID- 30195191
TI  - Amelioration of mitochondrial dysfunction in heart failure through S
      sulfhydration of Ca2+/calmodulin-dependent protein kinase II.
AB  - AIMS: Ca2+/calmodulin-dependent protein kinase II (CaMKII) plays a critical role
      in the development of heart failure and in the induction of myocardial
      mitochondrial injury. Recent evidence has shown that hydrogen sulfide (H2S),
      produced by the enzyme cystathionine gamma-lyase (CSE), improves the cardiac
      function in heart failure. However, the cellular mechanisms for this remain
      largely unknown. The present study was conducted to determine the functional role
      of H2S in protecting against mitochondrial dysfunction in heart failure through
      the inhibition of CaMKII using wild type and CSE knockout mouse models. RESULTS:
      Treatment with S-propyl-L-cysteine (SPRC) or sodium hydrosulfide (NaHS),
      modulators of blood H2S levels, attenuated the development of heart failure in
      animals, reduced lipid peroxidation, and preserved mitochondrial function. The
      inhibition CaMKII phosphorylation by SPRC and NaHS as demonstrated using both in
      vivo and in vitro models corresponded with the cardioprotective effects of these
      compounds. Interestingly, CaMKII activity was found to be elevated in CSE
      knockout (CSE-/-) mice as compared to wild type animals and the phosphorylation
      status of CaMKII appeared to relate to the severity of heart failure.
      Importantly, in wild type mice SPRC was found to promote S-sulfhydration of
      CaMKII leading to reduced activity of this protein, however, in CSE-/- mice S
      sulfhydration was abolished following SPRC treatment. INNOVATION AND CONCLUSIONS:
      A novel mechanism depicting a role of S-sulfhydration in the regulation of CaMKII
      is presented. SPRC mediated S-sulfhydration of CaMKII was found to inhibit CAMKII
      activity and to preserve cardiovascular homeostasis.

PMID- 30195192
TI  - The changing landscape of naloxone availability in the United States, 2011 -
      2017.
AB  - Opioid overdose deaths have been on the rise in the United States since 1999.
      Naloxone is a competitive opioid antagonist that rapidly reverses opioid
      overdose. The implementation of naloxone access laws and development of naloxone
      formulations that can be administered by laypersons have coincided with changes
      in the landscape of naloxone availability in the United States. Using data from
      IQVIA's National Prescription Audit(r) we present the number of naloxone
      prescriptions dispensed quarterly from 2011 through the second quarter of 2017.
      The data demonstrate that nationwide naloxone dispensing increased nearly eight
      fold from the fourth quarter of 2015 to the second quarter of 2017. Narcan(r) was
      the most commonly prescribed naloxone formulation as of the second quarter of
      2017, accounting for 68% of prescriptions during that quarter followed by
      Evzio(r) (20%). There was considerable variability in the extent to which states
      experienced increases in naloxone dispensing, which may represent a general state
      specific response to the opioid crisis, rather than direct association with
      opioid overdose death rates in a particular state. Although naloxone access laws
      continue to increase the amount of naloxone dispensed, cost remains a concern in
      terms of wide distribution of the life-saving medication.

PMID- 30195193
TI  - VALHUDES: A protocol for validation of human papillomavirus assays and collection
      devices for HPV testing on self-samples and urine samples.
AB  - BACK GROUND: Systematic reviews have concluded that hrHPV DNA testing using
      target-amplification tests is as accurate on vaginal self-samples as on clinician
      taken specimens for the detection of cervical precancer. However, insufficient
      evidence is available for specific HPV assay/self-sample device combinations.
      OBJECTIVES: The VALHUDES protocol is designed as a diagnostic test accuracy study
      that aims to compare the clinical sensitivity and specificity of particular hrHPV
      assay(s) on vaginal self-samples and first-void-urine, collected in agreement
      with standardized protocols, with hrHPV testing on matched clinician-taken
      samples. STUDY DESIGN: Five hundred enrolled women referred to a colposcopy
      clinic are invited to collect a first-void urine sample and one or more vaginal
      self-samples with particular devices before collection of a cervical sample by a
      clinician. Sample sets are subsequently analysed in a laboratory accredited for
      HPV testing. Disease verification for all enrolled patients is provided by
      colposcopy combined with histological assessment of biopsies. RESULTS: A first
      VALHUDES study has started in Belgium in December 2017 with enrolment from four
      colposcopy centres. The following assays are foreseen to be evaluated: RealTime
      High Risk HPV assay (Abbott), cobas-4800 and -6800 (Roche), Onclarity (BD), Xpert
      HPV (Cepheid) and Anyplex II HPV HR (Seegene). CONCLUSION: Given empirical
      evidence that the relative accuracy of HPV-testing on self- vs clinician-samples
      is robust across clinical settings, the VALHUDES protocol offers a framework for
      validation of HPV assay/self-sample device combinations that can be translated to
      a primary screening setting.

PMID- 30195194
TI  - Prognostic value of plasma brain natriuretic peptide value for patientswith
      sepsis: A meta-analysis.
AB  - PURPOSE: The aim of this meta-analysis was to clarify the diagnostic role of
      plasma BNP and NT-proBNP in predicting mortality for septic patients. METHODS: A
      systematic review was conducted prior to January 2018. Summary sensitivity,
      specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR) and
      diagnostic odds ratio (DOR) of the prognostic value of plasma BNP and NT-proBNP
      for septic patients. The area under the receiver operating curves (AUROC) were
      used to summarize overall test performance. RESULTS: Twenty-two studies with 3417
      septic patients were selected in the analysis. The summary sensitivity,
      specificity, PLR, NLR, DOR and the AUROC of the overall analysis of BNP were:
      0.84, 0.73, 3.1, 0.22, 14, 0.85; and these values of NT-proBNP were: 0.71, 0.73,
      2.6, 0.39, 7 and 0.7 respectively; Subgroup analysis and meta-regression analyses
      showed that the tested method and observation endpoint influenced the summary
      sensitivity, specificity of BNP, but the tested day, tested method or observation
      endpoint did not influence the summary sensitivity, specificity of NT-proBNP.
      CONCLUSIONS: This meta-analysis indicates that both elevated plasma BNP and NT
      proBNP have moderate predicts value for the mortality of septic patients, and the
      tested method and observation endpoint influence the results of BNP.

PMID- 30195195
TI  - The importance of the study of brain calcifications in patients with tuberous
      sclerosis complex.

PMID- 30195196
TI  - Circadian rhythms of melatonin and peripheral clock gene expression in idiopathic
      REM sleep behavior disorder.
AB  - OBJECTIVE: To evaluate changes in the expression of clock genes and melatonin
      levels in patients with idiopathic REM sleep behavior disorder (RBD) as a
      potential early stage of synucleinopathies. METHODS: We assessed the rhythmicity
      of circadian clock genes using real time-quantitative polymerase chain reaction
      and 24-h blood melatonin profiles using radio-immunoassay in 10 RBD patients and
      nine age-matched controls. RESULTS: The RBD patients did not show circadian
      rhythmicity for clock genes Per2, Bmal1, and Nr1d1 but the rhythmicity of Per 1
      remained, and the amplitude of Per3 was diminished. The 24-h melatonin rhythm did
      not differ between RBD patients and healthy control subjects. Melatonin profile
      in RBD patients was delayed by 2 h compared to controls, the habitual sleep
      phases were phase delayed by about 1 h, however no phase shift occurred in any of
      the clock genes studied. The control group had stable acrophases of melatonin
      rhythms of approximately 5 h whereas the RBD patients had a more dispersed range
      over 11 h. CONCLUSIONS: Our results suggest that RBD could be associated with
      altered expression of clock genes and delayed melatonin secretion. Thus, we argue
      that circadian system dysregulation could play a role in RBD.

PMID- 30195197
TI  - Alpha-synuclein aggregates in the parotid gland of idiopathic REM sleep behavior
      disorder.
AB  - BACKGROUND: The neuropathological hallmark of Parkinson's disease (PD) is the
      presence of aggregates of phosphorylated alpha-synuclein (pAS) in the nervous
      system. METHOD: We report a patient with video-polysomnography-confirmed
      idiopathic REM sleep behavior disorder that underwent parotidectomy because of
      parotid gland cancer. Immunohistochemistry of the gland tissue revealed abundant
      pAS deposits. One year after surgery the patient was diagnosed with PD. Prompted
      by this observation we examined the parotid gland in 10 consecutive individuals
      that underwent elective parotidectomy irrespective of their clinical condition.
      RESULTS: One had PD and another had mild parkinsonian signs plus reduced dopamine
      transporter uptake in the striatum. Both had pAS deposits in the parotid gland.
      The remaining eight subjects had no neurological signs and pAS was found in one
      of them. CONCLUSION: Our study shows that the parotid gland may contain pAS
      pathology in the prodromal stage of PD and in manifested PD.

PMID- 30195198
TI  - Sleep duration and remaining teeth among older people.
AB  - BACKGROUND: No studies have examined the associations between the numbers of
      teeth and sleep disturbance. Therefore, we examined the associations between the
      number of teeth and sleep duration in older people, considering the evidence
      linking fewer teeth and sleep apnoea through changes in jaw position. METHODS:
      For this study we used information from a sample of 23,444 cohort participants,
      randomly selected from the Japan Gerontological Evaluation Study 2010 (N =
      169,215). The outcome variable was self-reported sleep duration (h/day), and the
      explanatory variable was self-reported number of teeth (0, 1-9, 10-19, >=20). We
      treated age, sex, body mass index, educational attainment, annual equalized
      household income, depressive symptoms, physical activity, activities of daily
      living, presence of diabetes, and smoking status as covariates. Multinomial
      logistic regression was used among the 20,548 eligible participants with all
      necessary information. RESULTS: The mean age was 73.7 (standard deviation = 6.13)
      years. Most participants (28.1%) reported sleep duration of 7 h, while a small
      proportion of the participants reported short (<=4 h, 2.7%) or long (>=10 h,
      4.7%) sleep duration. The proportion of edentulous participants was 14.7%. Taking
      the 7-h sleep duration as the reference category, edentulous participants
      (relative risk ratio (RRR) = 1.43, 95% confidence interval (CI) = 1.07-1.90) or
      one to nine teeth (RRR = 1.29, 95% CI = 1.02-1.63) had a significantly higher
      relative risk ratio for short sleep, independent of covariates. Furthermore, they
      had a higher relative risk ratio for long sleep duration (RRR = 1.75, 95% CI =
      1.40-2.19; RRR = 1.48, 95% CI = 1.21-1.81, respectively). CONCLUSIONS: Compared
      to people with 20 or more teeth, older adults with fewer than 10 teeth have
      higher risks for short and long sleep durations.

PMID- 30195199
TI  - Automatic detection of cataplexy.
AB  - OBJECTIVE: Although being the most specific symptom of narcolepsy type 1 (NT1),
      cataplexy is currently investigated by clinical interview only, with potential
      diagnostic pitfalls. Our study aimed at testing the accuracy of an automatic
      video detection of cataplexy in NT1 patients vs. non-cataplectic subjects
      undergoing a standardized test with emotional stimulation. METHODS: Fifteen drug
      naive NT1 patients and 15 age- and sex-balanced non-cataplectic subjects
      underwent a standardized video recording procedure including emotional
      stimulation causing laughter. Video recordings were visually inspected by human
      scorers to detect three typical cataplexy facial motor patterns (ptosis, mouth
      opening and head drop), and then analysed by SHIATSU (Semantic-based HIearchical
      Automatic Tagging of videos by Segmentation using cUts). Expert-based and
      automatic attack detection was compared in NT1 patients and non-cataplectic
      subjects. RESULTS: All NT1 patients and none of the non-cataplectic subjects
      displayed cataplexy during emotional stimulation. Automatic detection correlated
      well with experts' assessments in NT1 with an overall accuracy of 81%. In non
      cataplectic subjects, automatic detection falsely identified cataplexy in two out
      of 15 (13.3%) subjects who showed active eyes closure during intense laughter as
      a confounder with ptosis. CONCLUSIONS: Automatic cataplexy detection by applying
      SHIATSU to a standardized test for video documentation of cataplexy is feasible,
      with an overall accuracy of 81% compared to human examiners. Further studies are
      warranted to enlarge the range of elementary motor patterns detected, analyse
      their temporal/spatial relations and quantify cataplexy for diagnostic purposes.

PMID- 30195200
TI  - Efficacy and safety of monoclonal antibody therapies for relapsing remitting
      multiple sclerosis: A network meta-analysis.
AB  - BACKGROUND: Several monoclonal antibodies have been licensed for relapsing
      remitting multiple sclerosis (RRMS). It is still unclear which treatment regimen
      should be recommended due to the lack of head-to-head randomized controlled
      trials (RCTs). This study aims to investigate the relative efficacy and safety of
      existing monoclonal antibody therapies in treating RRMS. METHODS: We searched
      PubMed, Embase, and the Cochrane Library for RCTs of monoclonal antibodies for
      treatment of RRMS. We performed a network meta-analysis to identify evidence
      comparing monoclonal antibodies with one another, interferon beta-1a (INFbeta
      1a), or placebo in adult patients with RRMS. The primary efficacy outcome was
      annualized relapse rate and the primary safety outcome was incidence rate of
      serious adverse events. RESULTS: A total of 14 eligible studies containing 9412
      patients treated with 7 regimens were analyzed. INFbeta-1a was the most common
      comparison treatment and showed an annualized relapse rate of 45.3%. All
      monoclonal antibody regimens, including natalizumab, natalizumab plus INFbeta-1a,
      alemtuzumab, daclizumab, and ocrelizumab, were associated with significant
      reduction in annualized relapse rate and similar risks of serious adverse events.
      Cluster analysis showed that natalizumab plus INFbeta-1a and alemtuzumab
      performed best in terms of high efficacy and safety. Natalizumab and daclizumab
      were characterized by high efficacy but relatively high risk of serious adverse
      events. Ocrelizumab was differentiated by high safety but relatively poor
      efficacy. CONCLUSION: This network meta-analysis provided a comprehensive summary
      of efficacy and safety of monoclonal antibodies for RRMS, which might provide a
      reference for treatment. More direct comparison studies are warranted.

PMID- 30195202
TI  - Alemtuzumab-containing reduced intensity conditioning allogenic hematopoietic
      stem cell transplantation in a case of primary progressive multiple sclerosis.
AB  - Increasing evidence has emerged lately regarding the use of autologous
      hematopoietic stem cell transplantation (HSCT) in the treatment of aggressive
      multiple sclerosis (MS). However, data is scarce regarding the use of allogenic
      HSCT in treating MS. We present a 42 years old male with aplastic anemia who
      underwent allogenic HSCT for severe aplastic anemia. This patient was diagnosed
      with primary progressive multiple sclerosis (PPMS) one-year post transplant and
      had to undergo a second HSCT due to his hematological disorder. His second HSCT
      was conditioned with an alemtuzumab containing regimen, after which his MRI and
      expanded disability status scale (EDSS) remained to be stable for 18 months.

PMID- 30195201
TI  - Low vitamin D-25(OH) level in Indonesian multiple sclerosis and neuromyelitis
      optic patients.
AB  - BACKGROUND: Vitamin D deficiency is commonly found in multiple sclerosis (MS) and
      Neuromyelitis Optic (NMO) patients and can impair the immunological status. As a
      tropical country, Indonesia has a lot of sunshine throughout the year as a source
      of vitamin D. The aim of this study was to evaluate and compare the serum vitamin
      D-25(OH) level in Indonesian MS and NMO patients to healthy individuals. METHODS:
      A cross-sectional study was conducted in Dr. Cipto Mangunkusumo General Hospital
      Jakarta from November 2016 to May 2017. Forty-eight patients (29 MS and 19 NMO)
      and 33 healthy controls were enrolled. We assessed the dietary recall, vitamin D
      supplementation, sunshine exposure, medication, annual relapse rate, and Expanded
      Disability Status Scale (EDSS). Vitamin D level was measured using direct
      competitive chemiluminescence immunoassay. RESULTS: Vitamin D deficiency was
      found in 48.4% of MS and 56.2% of NMO patients. The serum vitamin D level in MS
      and NMO groups was not significantly different from the healthy controls. Vitamin
      D level was not associated with EDSS and the annual relapse rate. Positive
      significant correlation was observed between sunshine exposure and vitamin D
      level in healthy control, but not evident in MS and NMO groups. MS and NMO
      subjects who still treated with corticosteroid had lower vitamin D level.
      CONCLUSION: Vitamin D deficiency is commonly found in Indonesian MS and NMO
      patients, but not associated with EDSS and annual relapse rate. Despite living in
      a country with adequate sunshine exposure, the physician should anticipate low
      serum vitamin D level, especially in MS or NMO patients who received
      corticosteroid.

PMID- 30195203
TI  - Removal of toluene from waste gas by adsorption-desorption process using corncob
      based activated carbons as adsorbents.
AB  - The aim of this study is to obtain activated carbons from corncob wastes by ZnCl2
      activation for toluene removal. Thermogravimetric analysis (TG), N2 adsorption
      desorption, scanning electron microscope (SEM), energy dispersive X ray
      spectroscopy (EDS), Fourier-transform infrared spectroscopy (FT-IR) and Boehm's
      titration were used to test the characteristics of raw materials and carbon
      samples. The influences of preparation conditions such as carbonization
      temperature, impregnation ratio and carbonization time on the textural and
      chemical characteristics of carbons were investigated. Besides, the effects of
      porosity and surface functional group on the adsorption capacity were also
      studied. The best adsorption capacity of 414.6 +/- 13.0 mg g-1 at 3000 mg m-3 was
      obtained when the condition was as follows: 1:1 impregnation ratio, 550  degrees
      C carbonization temperature and 1.0 h carbonization time. The Langmuir,
      Freundlich, Sips, Toth and Redlich-Peterson models were used to depict the
      adsorption mechanism of toluene on this sample. The recovery of toluene through
      vacuum swing adsorption (VSA)-temperature swing adsorption (TSA) process was also
      studied.

PMID- 30195204
TI  - iTRAQ-based quantitative proteomic analysis identified Eno1 as a cadmium stress
      response gene in Propsilocerus akamusi (Tokunaga) hemolymph.
AB  - Propsilocerus akamusi (Tokunaga) is a common species of midge in Siberia, Japan,
      and China and an important prey species for fish and aquatic birds. Furthermore,
      this species has been shown to have an extraordinary capacity to resist cadmium
      (Cd) toxicity. In this study, isobaric tags for relative and absolute
      quantitation (iTRAQ) coupled liquid chromatography tandem mass spectrometry (LC
      MS/MS) was used to analyze relative changes in the P. akamusi hemolymph proteome
      following exposure to a sublethal concentration of Cd2+. The results showed that
      Cd2+ stress affects energy metabolism in P. akamusi. After examining the
      differentially expressed proteins (DEPs), only one up-regulated protein
      associated with metabolism, alpha-enolase (Eno1) was identified and further
      isolated and characterized. Sequence alignments showed that the deduced P.
      akamusi Eno1 amino acid sequence is highly conserved, with similarities of 77-95%
      noted when compared to other Dipteran Eno1 sequences. Furthermore, prolonged Cd2+
      exposure impacted Eno1 transcription, protein expression and enzyme activity
      levels. These results suggest that Eno1 may play a role in the response to Cd2+
      stress in P. akamusi.

PMID- 30195205
TI  - Toxicity assessment of TiO2-MWCNT nanohybrid material with enhanced
      photocatalytic activity on Danio rerio (Zebrafish) embryos.
AB  - The increasing production and use of nanomaterials is causing serious concerns
      about their safety to human and environmental health. However, the applications
      of titanium dioxide nanoparticles (TiO2NP) and multiwalled carbon nanotubes
      (MWCNT) hybrids has grown considerably, due to their enhanced photocatalytic
      efficiency. To our knowledge, there are no reports available to the scientific
      community about their toxicity. In this work, we perform a toxicity assessment of
      TiO2NP and TiO2-MWCNT nanohybrid materials using Zebrafish embryos standardized
      96 h early life stage assay, under different exposure conditions (with and
      without UV light exposure). After exposure the parameters assessed were acute
      toxicity, hatching rate, growth, yolk sac size, and sarcomere length. In
      addition, MU-probe X-ray fluorescence spectroscopy (u-XRF) was employed to
      observe if nanoparticles were uptaken by zebrafish embryos and consequently
      accumulated in their organisms. Neither TiO2NP nor TiO2-MWCNT nanohybrids
      presented acute toxicity to the zebrafish embryos. Moreover, TiO2NP presents
      sublethal effects for total length (with and without UV light exposure) on the
      embryos. This work contributes to the understanding of the potential adverse
      effects of the emerging nanohybrid materials towards safe innovation approaches
      in nanotechnology.

PMID- 30195206
TI  - Low-concentration BPF induced cell biological responses by the ERalpha and GPER1
      mediated signaling pathways in MCF-7 breast cancer cells.
AB  - Bisphenol F (BPF), one of the alternatives to bisphenol A (BPA), can induce
      proliferation through the nuclear estrogen receptor ERalpha (estrogen receptor
      alpha) pathway in human breast cancer MCF-7 cells. However, the roles of membrane
      estrogen receptor GPER1 (G-protein-coupled receptor 1)-mediated signaling
      pathways in MCF-7 cell proliferation caused by BPF are unclear. The influence of
      BPF on MCF-7 cells was evaluated in terms of cell proliferation, intracellular
      calcium (Ca2+) fluctuations, and reactive oxygen species (ROS) generation. The
      molecular mechanisms of the cellular responses to low doses of BPF were studied
      through detecting the activations of ERalpha and GPER1-regulated PI3K/PKB or AKT
      (phosphatidylinotidol 3-kinase/protein kinase B) and ERK1/2 (extracellular-signa1
      regulated kinase 1/2) signals. At 0.01-1 MUM, BPF significantly promoted cell
      proliferation and elevated the levels of intracellular ROS and Ca2+. At these
      concentrations, BPF also significantly upregulated protein expressions of
      ERalpha, GPER1, c-myc, and cyclin D and phosphorylations of PKB and ERK1/2.
      Specific signal inhibitors decreased PKB and ERK1/2 phosphorylations and
      attenuated the effects of BPF. Silencing of GPER1 also significantly decreased
      BPF-induced cell proliferation. These results indicate that activating the GPER1
      PI3K/PKB and ERK1/2 signals by low doses of BPF can regulate the response of MCF
      7 cells and that ERalpha also influences the effects of exposure to BPF on the
      cells. The present study suggests a new mechanism by which BPF exerts relevant
      estrogenic action in cancer cells and also highlights the potential risks in
      using BPF as an alternative to BPA.

PMID- 30195207
TI  - The response of larvae Brachymystax lenok during continuous and single pulses
      exposure to copper, zinc, lead and cadmium.
AB  - The continuous and single pulses exposure of Cu, Zn, Pb and Cd on larvae
      Brachymystax lenok were tested in this study. The first-order kinetics was
      employed to obtain better comprehension on the time-toxicity relationship of
      tested heavy metals in continuous exposure test. For difference in time-varying
      exposure or recovery, 50% lethal time-averaged concentration (TAC) was used to
      assess the pulsed toxicity, which took both time and concentration into
      consideration in exposure and post-exposure period. TAC assessment to the single
      pulses and the regression analysis of first-order kinetic to continuous exposures
      demonstrated that Cu and Zn showed greater toxicity than Pb and Cd, indicating a
      slower uptake and/or depuration effect for zinc or copper. Furthermore, the
      results showed that recovery effect of larvae to all four metals was found in 24
      h exposure followed by 72 h in fresh water, while for 72 h exposure and 24 h non
      exposure the delayed lethal phenomenon occurred.

PMID- 30195208
TI  - Heavy metal pollution of oil-based drill cuttings at a shale gas drilling field
      in Chongqing, China: A human health risk assessment for the workers.
AB  - With the flourish of shale gas industry in China, the characteristic hazardous
      waste, oil-based drill cuttings (OBDC), was also produced in large quantities.
      Unlike traditional petroleum industry, shale gas exploitation covers a wider area
      and there are more well sites, the adverse effects of OBDC piled up around well
      sites are even greater. This study investigated the pollution status and leaching
      toxicity of eight heavy metals (Cd, Cr, Cu, Hg, Mn, Ni, Pb and Zn) in OBDC of
      shale gas exploitation, and evaluated the health risks of the drilling workers.
      The results showed that heavy metal pollution in OBDC was moderate, and the
      leaching toxicity was far below the standard value. Non-carcinogenic and
      carcinogenic risks of drilling workers were within an acceptable range.
      Meanwhile, in order to reduce the health risks of drilling workers, some
      suggestions are proposed to reduce the exposure risks of workers and the content
      of heavy metals in OBDC.

PMID- 30195209
TI  - Sulphur dioxide and arsenic affect male reproduction via interfering with
      spermatogenesis in mice.
AB  - As two potential environmental hazards, sulphur dioxide (SO2) and arsenic have
      adverse effects on male reproduction, but the mechanism of which and their
      combined toxicity are not clear. In this study, we investigate male reproductive
      toxicity with a focus on spermatogenesis by treating mice with 5 mg/m3 SO2 and/or
      5 mg/L arsenic. Our results showed that arsenic exposure caused significant
      decreases in water and food consumption and body weight in mice, whereas these
      changes were not observed in the SO2-only group. Both SO2 and arsenic reduced
      sperm counts, increased the percentage of sperm malformation, and induced
      abnormal testicular pathological changes. Elevated H2O2 and MDA contents,
      declined T-SOD activity, decreased spermatogenic cell counts, enhanced caspase-3
      activity, and increased TUNEL-positive cells were also observed in mice exposed
      to SO2 and/or arsenic. Moreover, SO2 and arsenic co-exposure changed the mRNA
      levels of Bax and Bcl-2, decreased serum testosterone levels, and downregulated
      the expression of steroidogenic-related genes (LHR, StAR, and ABP) in mice. These
      findings provide a new theoretical basis for understanding how SO2 and arsenic
      interfere with spermatogenesis leading to infertility. These results also suggest
      that SO2 and arsenic co-exposure likely result in an additive effect on male
      reproductive toxicity in mice.

PMID- 30195210
TI  - Quality of life among parents of children with visual impairment: A literature
      review.
AB  - AIMS: To describe the experience of parents caregiving children with visual
      impairment (VI), to determine how their quality of life (QoL) is assessed, and to
      summarize QoL indicators through a review of the literature. METHODS: A thematic
      search through PubMed, PsycINFO, ProQuest and ERIC databases was performed of
      articles published in English in peer-reviewed journals between 1996 and 2016.
      Publications were included if they referred to both children or adolescents with
      VI and their parents, or the family context. The complete selection process
      disclosed 37 papers suitable for review. RESULTS: Researchers mainly used ad hoc
      interviews and questionnaires to investigate this topic. Two specific tools, the
      CarCGQoL (congenital glaucoma) and the OTI (congenital cataract), were
      identified. Most of the information collected referred to the parents' opinion
      concerning professional services, their needs and worries, the impact of VI on
      their emotional well-being and the strategies to assist parents to cope and
      adjust to the situation. CONCLUSIONS: The experience of caring for a child with
      VI is mainly influenced by psychosocial factors. Information and guidance to
      understand the child's visual condition are insufficient, and the available
      resources reinforce concerns of caregivers regarding the child's opportunities,
      expressed as negative emotional reactions.

PMID- 30195211
TI  - Identification of candidate olfactory genes in cicada Subpsaltria yangi by
      antennal transcriptome analysis.
AB  - Olfaction in antennae is essential for regulating insect behaviors such as host
      preference and oviposition site selection. To better understand the olfactory
      mechanisms in the cicada Subpsaltria yangi that has a very narrow host range far
      fewer than diets of most other cicadas, an antennal transcriptome was constructed
      in this study. We identified 10 unigenes encoding putative odorant-binding
      proteins (OBPs), 10 chemosensory proteins (CSPs), 8 sensory neuron membrane
      proteins (SNMPs), 7 gustatory receptors (GRs), 29 odorant receptors (ORs) and 13
      ionotropic receptors (IRs). We found that the OBPs were separated into two
      groups, Classic OBPs and Plus-C OBPs, according to their motifs. Based on
      sequence alignment and phylogenetic analysis, we found five Orcos in OR family.
      However, no pheromone receptor was identified, which may be related to that
      cicadas are sound-producing insects and acoustic signals other than pheromones
      play most important role in sexual communication. We used qRT-PCR to examine the
      expression profile of ten OBPs genes in various organs, and found that they were
      mainly expressed in olfactory organs such as antennae and mouthparts. Our results
      make it possible for future research of the olfactory system of S. yangi at the
      molecular level, and provide important bases for elucidation of the molecular
      mechanisms and evolution of chemosensation in sap-sucking insects.

PMID- 30195212
TI  - A whole-body transcriptome analysis and expression profiling of odorant binding
      protein genes in Oedaleus infernalis.
AB  - To investigate the olfactory mechanisms in Oedaleus infernalis, one of important
      pests of cereals and pasture in the northern China, the whole-body transcriptome
      was constructed by RNA-Seq in this study. By de novo assembly, a total of 92,476
      unigenes were generated in the adult sample, and 32,693 unigenes (35.35%) were
      successfully annotated by Blastx. Eighteen putative odorant binding proteins
      (OBPs) were identified, and phylogenetic analysis indicated the closest genetic
      relationship of eight OBPs in O. infernalis with those in its sibling species,
      Oedaleus asaiticus, while five OBPs in O. infernalis with those in Locusta
      migratoria. qRT-PCR analysis of the expression patterns of all 18 OinfOBPs in
      different tissues indicated that most OinfOBPs, especially OinfOBP7 and
      OinfOBP12, had higher expression levels in the antennae meanwhile no or faint
      expression in other body parts, including heads (without antennae), thoraxes,
      abdomens, legs, and wings, suggesting that these OBPs may play important roles in
      olfaction. OinfOBP2 was highly expressed only in male heads. Interestingly, only
      OinfOBP13 displayed high expressions in nearly all tested tissues. These two OBPs
      may have different physiological functions in O. infernalis. The remaining OBPs
      were not or weakly detected in all tested tissues. Our results provide important
      molecular information for further studies on chemosensory mechanisms in this
      pest.

PMID- 30195213
TI  - Assessment of potential biomarkers of pre-receptive and receptive endometrium in
      uterine fluid and a functional evaluation of the potential role of CSF3 in
      fertility.
AB  - The endometrium lines a women's uterus becoming receptive, and allowing embryo
      implantation to occur, for just a few days during the post-ovulatory mid
      secretory phase of each menstrual cycle. We investigated whether concentrations
      of proposed receptivity biomarkers (VEGF, IL8, FGF2, CSF3 sFlt-1, sGP130 and
      PlGF) secreted by the endometrium into the uterine cavity and forming the
      microenvironment for embryo implantation is altered among a population of age
      matched women with unexplained (idiopathic) infertility compared to fertile women
      during the receptive mid-secretory phase (n = 16 fertile, 18 infertile) and the
      prior pre-receptive early secretory phase (n = 19 fertile, 18 infertile) of their
      cycle. In the mid-secretory cohort significantly elevated concentrations of five
      biomarkers; PlGF (p = 0.001), IL8 (p = 0.004), sGP130 (p = 0.009), sFlt-1 (p =
      0.021), and CSF3 (p = 0.029) was present in uterine fluid of infertile women
      during the mid-secretory phase, but only CSF3 was significantly elevated in the
      pre-receptive early secretory phase (p = 0.006). In vitro studies of glycosylated
      and non-glycosylated forms of CSF3 at representative fertile (20 ng/mL) and
      infertile (70 ng/mL) effects on endometrium and embryo behaviour were performed.
      Non-glycosylated CSF3 at fertile concentrations significantly (p < 0.001)
      elevated endometrial epithelial cell proliferation however chronic treatment or
      elevated (infertile) concentrations of CSF3 in glycosylated form abrogated the
      positive effects. Both forms of CSF3 increased trophoblast cell invasion (p <
      0.001) regardless of concentration. Mouse embryo outgrowth was significantly (p <
      0.01) increased at fertile but not at infertile concentrations. The study
      confirmed potential utility of five biomarkers of endometrial receptivity for
      future application in the mid-secretory phase while highlighting CSF3 is elevated
      in the earlier pre-receptive phase. Our data provides evidence that CSF3 acts on
      both human endometrium and embryo in a manner that is concentration and
      glycosylation dependent.

PMID- 30195214
TI  - Molecular mechanistic insights into uncoupling of ion transport from ATP
      synthesis.
AB  - A procedure is evolved to assess the maximum uncoupling activity of the classical
      unsubstituted phenolic uncouplers of mitochondrial oxidative phosphorylation (OX
      PHOS) 2,4-dinitrophenol and 2,6-dinitrophenol. The uncoupler concentrations, C,
      required for maximum uncoupling efficacy are found to be a strong function of the
      pH, and a linear relationship of pC with pH is obtained between pH 5 to pH 9. The
      slopes of the uncoupler concentrations in the aqueous and lipid phases as a
      function of pH have been estimated. It is shown that the experimental results can
      be derived from first principles by an enzyme kinetic model for uncoupling that
      is based on the same equations as formulated for the coupling of ion transport to
      ATP synthesis in a companion paper after imposition of the special conditions
      arising from the uncoupling process. The results reveal the catalysis of a
      reaction that involves both the anionic and protonated forms of the phenolic
      uncouplers in the vicinity of their binding sites in a non-aqueous region of the
      cristae membranes of mitochondria. The rate-limiting step in the overall process
      of uncoupling has been identified based on the uncoupling data. The data cannot
      be explained by a simple conduction of protons by uncouplers from one bulk
      aqueous phase to another as postulated by Mitchell's chemiosmotic theory. It is
      shown that Nath's two-ion theory of energy coupling/uncoupling in ATP synthase is
      consistent with the results. A molecular mechanism for uncoupling of ATP
      synthesis by the dinitrophenols is presented and the chief differences between
      coupling and uncoupling in ATP catalysis are summarized. The pharmacological
      consequences of our analysis of uncoupling are discussed, with particular
      reference to the mode of action of the anti-tuberculosis drug bedaquiline that
      specifically targets the c-subunit of the F1FO-ATP synthase and uncouples
      respiration from ATP synthesis in Mycobacterium tuberculosis. Hence the work is
      shown to be important both from the point of view of fundamental biology and is
      also pregnant with possibilities for practical pharmaceutical applications.

PMID- 30195215
TI  - An empirical analysis of enzyme function reporting for experimental
      reproducibility: Missing/incomplete information in published papers.
AB  - A key component of enzyme function experiments is reporting of considerable
      metadata, to allow other researchers to replicate, interpret properly or use
      fully the results. This paper evaluates the completeness of enzyme function data
      reporting for reproducibility. We present a detailed examination of 11 recent
      papers (and their supplementary material) from two leading journals. We found
      that in every paper we were not able to collect some critical information
      necessary to reproduce the enzyme function findings. Study of 100 papers used by
      the SABIO-RK database confirmed some of the most common omissions: concentration
      of enzyme or its substrates, identity of counter-ions in buffers. A computer
      system should be better at preventing such omissions, helping secure the
      scientific record. Many of the omissions found would be trapped by the currently
      available version of STRENDA DB.

PMID- 30195216
TI  - Walking balance on a treadmill changes during pregnancy.
AB  - BACKGROUND: Altered standing balance during pregnancy has been previously
      reported. To date, body center of mass (bCOM) motion has not been used to track
      balance changes in this population. We recently compared three methods to
      determine the torso center of mass (tCOM) location (via force plate acquired
      center of pressure calculation, using Pavol surface anthropometry measurements,
      and a combination of the two) to use in calculating the bCOM during pregnancy.
      RESEARCH QUESTION: This current research explored two questions: (1) does walking
      balance change during pregnancy, and (2) do the methods for identifying tCOM
      location affect the resulting balance measures? METHODS: Fifteen pregnant women
      were recruited to perform 60-second trial of treadmill walking at 4-week
      intervals from 12 weeks gestation until delivery. Walking balance was measured as
      bCOM motion within the base of support. Gestation time and anthropometric model
      (force plate, Pavol, and combination) were repeated-measures independent
      variables in a general linear mixed model analysis. RESULTS: There was a
      significant decrease in walking balance during pregnancy. As gestation
      progressed, we observed non-linear changes in the bCOM motion within the base of
      support over time, with some changes starting early in pregnancy and others not
      starting until late 2nd trimester. The anthropometric model used to locate the
      bCOM significantly influences balance measures. The results of this study
      indicate that the force plate method is more appropriate for locating the tCOM in
      the anterior and lateral directions. SIGNIFICANCE: The results of this study will
      inform clinicians and patients about the gestational stage-associated changes in
      balance during pregnancy that increase the risk of falling and injury.
      Researchers should also carefully consider the method for locating the bCOM.

PMID- 30195217
TI  - Association of walk ratio during normal gait speed and fall in community-dwelling
      elderly people.
AB  - BACKGROUND: Walk ratio (WR), calculated by dividing step length by cadence, can
      be used to represent the gait characteristics of human beings to maintain their
      gait speed. RESEARCH QUESTION: The aim of this study was to examine whether WR
      could distinguish fallers from community-dwelling elderly people. METHODS: We
      recruited 9205 elderly people (mean age: 73.7 +/- 5.6 years, 4218 men and 4987
      women) from the National Center for Geriatrics and Gerontology - Study of
      Geriatric Syndromes. Fall history was assessed by face-to-face interview, and
      "fallers" were defined as people who had fallen at least once within the past
      year. WR was calculated as corrected step length divided by corrected cadence,
      and we divided the subjects into three groups according to the tertile of WR (T1,
      T2, and T3). We also stratified the participants by gait speed (<1.0 or >=1.0
      m/s). RESULTS: With reference to the T3 group, the T1 group had a higher odds
      ratio (OR) of falling in the past year [OR: 1.24, 95% confidence interval (CI):
      1.09-1.41], even after adjusting for other covariates. After stratification by
      gait speed, the same multivariate analyses were conducted. In the participants
      who walked at 1.0 m/s or faster, the T1 group had a higher OR [1.27, 95%
      confidence interval (CI): 1.10-1.48], while there was no significant association
      with fall rate among those who walked slower than 1.0 m/s. SIGNIFICANCE: This
      study revealed that the smallest WR was independently associated with falling in
      the past year among community-dwelling elderly people, especially elderly people
      with no deterioration of gait speed. These results suggest that intervention
      regarding gait pattern, especially WR, would help to prevent falls.

PMID- 30195218
TI  - Difference scores between single-task and dual-task gait measures are better than
      clinical measures for detection of fall-risk in community-dwelling older adults.
AB  - BACKGROUND: As the proportion of older adults in the population increases, so
      does the associated prevalence of falls, making falls the leading cause of fatal
      and nonfatal injuries among adults aged >=65 years. In response, researchers and
      clinicians seek to develop a clinical tool that accurately predicts fall risk.
      These Investigations have included measures of clinical mobility and balance
      tests, strength, physiologically based tests, postural sway, and mean and
      variability of gait measures. To date, no study has concurrently explored all
      these measures to determine which measures, alone or in combination, emerge as
      the most predictive of fall risk. While there is evidence that dual-task gait
      conditions are sensitive indicators of fall risk, difference scores between dual
      task and single-task gait conditions (DS) have not been explored. RESEARCH
      QUESTION: This study included outcome measures representing diverse domains
      (clinical mobility and balance, strength, physiological, postural sway, and mean
      and variability of difference scores between dual- and single-task gait
      conditions) to determine the combination of measures that were the most sensitive
      for retrospectively classifying fallers from non-fallers. METHODS: Forty-two
      (mean: 75.8 yrs +/- 3.3) community-dwelling older adults completed a
      comprehensive battery of 76 measures and classified into two groups based on self
      report of having one or more falls in the previous year. RESULTS: Results suggest
      that 11 measures captured the salient characteristics of the total cohort
      (fallers (N = 27) and non-fallers (N = 15) and that five gait measures were
      sufficient for correctly classifying fallers and non-fallers with 92.3%
      sensitivity and 66.7% specificity with a total model classification of 82.9%.
      SIGNIFICANCE: The five variables comprise mean DS of stride timing, stride width,
      and stride length and DS in variability for stride width and stride velocity
      demonstrating that difference in performance between dual-task and single-task
      gait trials was essential for discriminating fallers and superior to other
      measures.

PMID- 30195219
TI  - Treadmill-based gait-slip training with reduced training volume could still
      prevent slip-related falls.
AB  - BACKGROUND: Treadmill-based gait-slip training shows to be effective in reducing
      the risk of slip-related falls. In previous relevant studies, the number of
      repeated slip perturbations ranged from 12 to 30. RESEARCH QUESTION: It is
      unclear if a reduced number of treadmill-slips can still yield adaptive
      strategies to lower the likelihood of falls after a slip over ground. This study
      examined if eight repeated slips on a treadmill reduced the risk of falls among
      young adults when they were exposed to a novel overground slip. METHODS: Forty
      three healthy young adults were randomized into either training or control group.
      The training group underwent an 8-slip perturbation training procedure on a
      treadmill while the control group received the same number of normal walking
      trials on the same treadmill. Following the training, both groups were exposed to
      an unrehearsed slip during overground walking. Their body's reactions to the
      novel overground slip were collected by a motion capture system. RESULTS: The
      training group exhibited significantly better reactions to the slip than did the
      control group, evidenced by the lower fall proportion and improved dynamic
      stability at recovery foot touchdown during the overground slip. No improvement
      in dynamic stability was detected in the training group at the slipping foot
      touchdown and recovery foot liftoff. SIGNIFICANCE: The results suggested that the
      shortened perturbation training program may be efficacious in improving responses
      to a novel overground slip but may not be as effective as protocols using greater
      number of slips. This study could provide guidance for selecting the number of
      slips for future perturbation-based training protocols.

PMID- 30195220
TI  - Gait analysis of patients with continuous proximal sciatic nerve blockade in
      flexion contractures after primary total knee arthroplasty.
AB  - BACKGROUND: The main objective of total knee arthroplasty is to relieve pain,
      restore normal knee function, and improve gait stability. Significant flexion
      contractures can severely impair function after surgery. The purpose of this
      study is to evaluate the efficacy of implementing a continuous proximal sciatic
      nerve block in conjunction with aggressive physical therapy to treat patients
      with persistent flexion contractures that were recalcitrant to rehabilitation
      efforts following primary total knee arthroplasty (TKA). METHODS: From December
      2012 to January 2016, the following subjects were enrolled in this study: 20
      patients (15 females and 5 males aged between 62 and 78 years old; median age =
      65.7 y) with flexion contractures ranging from 15 degrees  to 25 degrees  (19.2
      degrees +/-5.6 degrees ) that persisted for at least 1.5 months following total
      knee arthroplasty and showed no significant improvement in response to
      conventional therapeutic methods. Demographic data, the passive range of motion,
      flexion contracture, pain score during stretching, and the Hospital for Special
      Surgery knee score were recorded. A portable motion analyzer was used to obtain
      the corresponding gait parameters from the flexion contractures group and control
      group. Repeated measurement ANOVA was used to compare the clinical results.
      RESULTS: In combination with 2 to 4 (2.5 +/- 1.3) months of aggressive knee
      stretching exercises, 16 out of 18 knees achieved full extension, and 2 out of 18
      improved to within 5 degrees  of the full extension. An average of the 12 to 48
      (26.6 +/- 10.7) month follow-up showed that this improved range of motion was
      maintained for all the corresponding patients, and that there were no
      reoccurrences of deformity. The mean Hospital for Special Surgery knee scores
      improved from 61.2 to 93.2 points (p < 0.001). After six months of continuous
      proximal sciatic nerve blockage, all gait parameters for the flexion contractures
      group exhibited significant improvement. CONCLUSION: A continuous proximal
      sciatic nerve block could be a useful adjunct to a physical therapy regimen for
      patients with knee flexion contractures, especially for patients with difficult
      to-treat cases of knee flexion contracture that are recalcitrant to conservative
      therapy.

PMID- 30195221
TI  - How do children with bilateral spastic cerebral palsy manage walking on inclines?
AB  - BACKGROUND: Walking on inclined surfaces is an everyday task, which challenges
      stability and propulsion even in healthy adults. Children with cerebral palsy
      adapt similarly to inclines like healthy children do. However, how stability and
      propulsion in these subjects are influenced by different inclines remained
      unaddressed as of yet. RESEARCH QUESTION: The aim was to examine the feeling of
      safety, stability and propulsion of children with cerebral palsy when walking on
      inclines to gain insight into the challenges they might face on these conditions.
      METHODS: Eighteen children with bilateral spastic cerebral palsy with gross motor
      function classification scale level I and II and nineteen healthy children
      underwent instrumented 3D gait analysis on level ground and on a 5 degrees  and a
      10 degrees  incline. A mixed linear model was used to draw between and within
      group comparisons. RESULTS: Reduced lateral trunk sway, a relative lengthening of
      the lower limb at initial contact and a controlled walking speed were employed
      during downhill gait compared to level walking. Patients showed an increased
      sagittal ROM of trunk (3-4 degrees ) and pelvis (2-3 degrees ) and a decreased
      sagittal knee ROM (13 degrees ) compared to the typically developed children.
      During uphill gait, an insufficient increase of push-off power at the ankle
      (increase by 0.48 W/kg) was noted in children with CP, which appeared to lead to
      particularly shorter strides (about 0.1 m) in patients compared to healthy
      children (increase by 1.32 W/kg). SIGNIFICANCE: Depending on inclination angle,
      children with cerebral palsy managed to walk on inclines in a controlled manner.
      The steeper the incline, the more the gait appeared to be affected: decreased
      feeling of safety, increased need for stabilising mechanisms for downhill gait
      and less sufficient uphill propulsion were seen. Helping these patients to attain
      better control during downhill gait and strengthening uphill gait mechanisms may
      support their participation in everyday life.

PMID- 30195222
TI  - Numerical optimization of membrane module design and operation for a full-scale
      submerged MBR by computational fluid dynamics.
AB  - The hydrodynamics in the membrane module of a full-scale sMBR at 500 m3/d was
      simulated by computational fluid dynamics (CFD) in this study. Several key
      indexes, including membrane distance (d), aeration design, height of gas-liquid
      dispersion hm, and freeboard height hf and operational conditions, including SADp
      and liquid viscosity, were optimized through investigating their impacts on water
      velocity distribution and membrane shear stress. The CFD model was validated by
      comparing the simulated trace element RTD curves with experimental results. The
      optimal design and operational parameters for the full scale sMBR are as
      following: membrane distance d = 35 mm, air diffusers parallel located 75-100 mm
      under the bottom of the membrane module, the free board height hf adjusted to 400
      mm, and the SADp recommended as 20 in the full-scale MBR studied.

PMID- 30195223
TI  - Temperature shapes the microbiota in anaerobic digestion and drives efficiency to
      a maximum at 45  degrees C.
AB  - Throwing longstanding habits over the pile may be necessary to improve biogas
      production, in particular when it comes to the process temperature. Its effect on
      biogas production was investigated with lab-scale reactors operated in fed-batch
      mode (cattle slurry and maize straw) at 10-55  degrees C over six months.
      Biochemical and microbial changes were comprehensively investigated. Production
      was highest and most efficient at 45  degrees C with an average methane yield of
      166 NL kg-1 VS, and thus 12.8% and 9.6% higher than at 37 and 55  degrees C.
      Temperature significantly affected the microbiota and higher temperature provoked
      a shift from Bacteroidetes/Proteobacteria to Firmicutes. A transition from
      hydrogenotrophic to acetoclastic methanogenesis was observed from 10 to 45 
      degrees C, while the trend was reversed at 55  degrees C. The results contest the
      textbook notion of preferred and most efficient temperatures for AD and suggest
      reconsideration of the temperature range around 45  degrees C for efficient
      manure-based co-fermentation.

PMID- 30195224
TI  - Performance and kinetic model of degradation on treating pharmaceutical solvent
      wastewater at psychrophilic condition by a pilot-scale anaerobic membrane
      bioreactor.
AB  - A pilot-scale anaerobic membrane bioreactor (AnMBR) was operated for 435 days in
      this study, aiming to treat pharmaceutical solvent wastewater containing m-Cresol
      (MC), isopropanol (IPA) and N,N-Dimethylformamide (DMF) pollutants at different
      temperatures of 35 +/- 3  degrees C, 25 +/- 3  degrees C, 15 +/- 3  degrees C and
      25 +/- 3  degrees C, respectively. The reactor reached average total removal
      efficiencies of about 96%, 97.2% and 98% of MC, IPA and DMF at psychrophilic
      condition (15 +/- 3  degrees C). Higher physical removal rate was obtained at 15
      +/- 3  degrees C due to the important contribution of membrane filtration. At
      this stage, the biogas production, methane content and specific methanogenic
      activity and extracellular polymeric substances of suspended sludge were observed
      with the lowest level. Moreover, the kinetic models for solvent degradation were
      established at different temperatures, results showed the smaller maximum
      specific substrate degradation rate of MC and IPA, besides, the lowest
      degradation rate of three solvents were obtained at 15 +/- 3  degrees C.

PMID- 30195225
TI  - Evaluation of the action of Tween 20 non-ionic surfactant during enzymatic
      hydrolysis of lignocellulose: Pretreatment, hydrolysis conditions and lignin
      structure.
AB  - The aim of this work was to study the effects of pretreatment process, hydrolysis
      condition and structural features of lignin on the improving action of
      surfactants (Tween 20) for enzymatic hydrolysis of pretreated wheat straw, and
      further to interpret the relation of these factors with the non-productive
      adsorption of cellulases on lignin. Tween 20 seemed to be more greatly improve
      cellulose conversion under harsher conditions. The surfactant showed more
      significant improvement for acid-pretreated substrates than oxidative-pretreated
      substrates. Highly-condensed lignin and phenolic hydroxyl groups showed much
      stronger adsorption ability to cellulases, while Tween 20 could well block the
      lignin-cellulase interactions recovering cellulose hydrolyzability. It was
      proposed that pretreatments altered lignin structures, resulting in the change of
      surface properties thus further impacting the lignin-cellulase interactions.
      Addition of Tween 20 could modify lignin surface properties to change its
      hydrophobicity, hydrogen bonding ability and surface charges, thus reducing the
      non-productive adsorption of proteins.

PMID- 30195226
TI  - Impacts of energy distribution and electric field on membrane fouling control in
      microbial fuel cell-membrane bioreactor (MFC-MBR) coupling system.
AB  - To investigate the influence of energy allocation on membrane fouling, three
      coupling systems at different concentrations of mixed liquid suspended solids
      (MLSS) and a control system without microbial fuel cell (MFC) were established.
      The results show that MFC acted negative effect in low-loading stage (0.59 kg
      COD.m-3.d-1), while high MLSS acted active effect on organics degradation in high
      loading stage (2.00 kg-COD.m-3.d-1), and electric field could be a positive
      factor with sufficient energy. Besides, membrane filtration experiments in the
      electric field with microbial contaminants indicate that soluble microbial
      products (SMP) and loosely bound extracellular polymeric substances (LB-EPS) had
      greater tendencies to cause irreversible membrane fouling. SMP and the residual
      cell liquid (Cell) were more susceptible than extracellular polymeric substances
      (EPS), demonstrating that the irreversible fouling was reduced mainly due to SMP
      decrease in the electric field.

PMID- 30195227
TI  - Production of liquefied fuel from depolymerization of kraft lignin over a novel
      modified nickel/H-beta catalyst.
AB  - In this study, a novel modified nickel/H-beta (Ni/DeAl-beta) catalyst, which has
      active acidic sites and hydrogen binding sites, was prepared and used to produce
      liquefied fuel from lignin. The bifunctional Ni/DeAl-beta catalyst efficiently
      converted kraft lignin into liquefied fuel due to the synergistic effect of
      aluminum Lewis acid sites and nickel hydrogen binding sites. At a nickel content
      of 0.6 mmol/gzeolite, the Ni/DeAl-beta catalyst gave a high liquid product yield
      of 88.6% at 300  degrees C for 36 h. Most of the liquid product was dissolved in
      petroleum ether (73% of 88.6%), which was mainly composed of monomeric and
      dimeric degradation products. Under these conditions, the higher heating values
      (HHV) increased from 24.9 MJ/kg for kraft lignin to 32.0 MJ/kg for the liquid
      product. These results demonstrated the bifunctional Ni/DeAl-beta catalyst could
      be an efficient catalyst for lignin to liquefied fuel conversion.

PMID- 30195228
TI  - miR-143 and miR-145 promote hypoxia-induced proliferation and migration of
      pulmonary arterial smooth muscle cells through regulating ABCA1 expression.
AB  - BACKGROUND: Excessive proliferation and migration of pulmonary artery smooth
      muscle cells (PASMCs) play an important role in the occurrence and development of
      pulmonary arterial hypertension (PAH). miR-143/145 was reported to be up
      regulated in the animal models and PAH patients, and deletion of miR-143/145
      cluster prevented the development of hypoxia-induced pulmonary hypertension, but
      its underlying mechanism has not been elucidated. METHODS: qRT-PCR and Western
      blot were performed to detect the expressions of miR-143/145 and ATP-binding
      cassette transporter A1 (ABCA1) in PAH patients and PASMCs under hypoxic
      conditions. Cell proliferation and migration were assessed by Cell Counting Kit-8
      and wound-healing assay, respectively. Luciferase reporter assay and RNA
      immunoprecipitation were conducted to confirm the interaction between miR-143/145
      and ABCA1. Hypoxia-induced PAH rat model was established to confirm the functions
      of miR-143/145 in the pathogenesis of PAH and its underlying mechanism in vivo.
      RESULTS: miR-143 and miR-145 were up-regulated and ABCA1 was down-regulated in
      PAH patients and PASMCs under hypoxic conditions for different time, as well as
      hypoxia-induced PAH rats. miR-143/145 inhibition and ABCA1 overexpression
      suppressed hypoxia-induced proliferation and migration in PASMCs. ABCA1 was
      identified as a direct target of miR-143/145 in PASMCs. Moreover, ABCA1 partially
      reversed miR-143/145-mediated promotion of hypoxia-induced cell proliferation and
      migration in PASMCs. Furthermore, in vivo experiments confirmed that inhibition
      of miR-143/145 prevents hypoxia-induced pulmonary hypertension and pulmonary
      vascular remodeling by targeting ABCA1. CONCLUSION: miR-143/145 promoted hypoxia
      induced proliferation and migration of PASMCs by targeting ABCA1, contributing to
      better understanding of the mechanism underlying the pathogenesis of PAH.

PMID- 30195229
TI  - Impulse control difficulties while distressed: A facet of emotion dysregulation
      links to Non-Suicidal Self-Injury among psychiatric inpatients at military
      treatment facilities.
AB  - Links between emotion dysregulation, suicide ideation, and suicidal versus non
      suicidal self-injury (NSSI) are poorly understood within military samples. United
      States service members and beneficiaries (N = 186), psychiatrically hospitalized
      following a suicidal crisis, completed the Difficulties in Emotion Regulation
      Scale (DERS; Gratz & Roemer, 2004), and reported lifetime suicide ideation,
      attempts, and NSSI. We expected that emotion dysregulation would positively
      associate with worst lifetime suicide ideation, multiple suicide attempt status,
      and lifetime NSSI. Suicide ideation severity and multiple suicide attempts did
      not associate with DERS components. Notably, difficulties with impulse control
      (feeling out of control while distressed) was positively associated with NSSI
      history. Theoretical models that clearly describe the role of emotion
      dysregulation in suicidal thoughts, its progression to suicidal actions, and NSSI
      are needed to advance clinical care for this highly vulnerable group.
      Longitudinal and micro-longitudinal study designs require further investigation.

PMID- 30195230
TI  - Factorial structure of the Patient Health Questionnaire-9 as a depression
      screening instrument for university students in Cartagena, Colombia.
AB  - Previous studies on the factorial structure of the Patient Health Questionnaire
      (PHQ-9) have yielded divergent results, and there is no consensus on which
      factorial structure provides a more adequate fit. In Colombia, no precise method
      to estimate the factorial structure of the PHQ-9 has been used. The purpose of
      this study is to evaluate the factorial structure of the PHQ-9 as a depression
      screening tool in university students of Colombia from a model of two factors
      previously studied. The PHQ-9 was applied to 550 health science university
      students. A factorial confirmatory analysis was carried out using a structural
      equations model and invariance analysis. The model with one somatic factor and
      one non-somatic factor, achieved a better fit with invariance by gender. The PHQ
      9 used as a depression screening tool used in university students in Cartagena
      revealed two factors, one somatic and one non-somatic with measurement invariance
      by gender.

PMID- 30195231
TI  - Reduced scanning of salient facial features mediates the association between
      paranoia and emotion recognition.
AB  - The vigilance-avoidance hypothesis of paranoia states that in paranoia visual
      attention is shifted away from threat-related stimuli. This may be an explanation
      for reduced scanning of salient facial features in psychosis and subsequently
      impaired emotion recognition. Here, we explored whether higher levels of paranoia
      would predict reduced visual attention to salient facial features and impaired
      emotion recognition and whether reduced visual attention to salient facial
      features mediates the association between paranoia and errors in emotion
      recognition. Participants with schizophrenia (SZ, n = 22) and healthy controls
      (HC, n = 19) completed questionnaire assessments of paranoia and negative
      symptoms and conducted an emotion recognition task comprised of dynamic facial
      stimuli. Additionally, visual attention (number of fixations) to salient facial
      features was assessed using eye-tracking. SZ made more errors in affect
      recognition than HC. Visual attention to salient facial features did not differ
      between SZ and HC but significantly mediated the significant association between
      paranoia and errors in the emotion recognition task in the complete sample.
      Negative symptoms also predicted errors in emotion recognition but this
      association was not mediated by visual attention. Our findings are in line with
      the avoidance-assumption of a vigilance-avoidance hypothesis of paranoia, in
      which correct facial emotion recognition is prevented due to an avoidance of
      salient facial features.

PMID- 30195232
TI  - Openness to firearm storage safety as a suicide prevention tool among those
      exposed to suicide: The role of perceived closeness to the suicide decedent.
AB  - BACKGROUND: Exposure to suicide and closeness to a suicide decedent may be
      relevant to means safety, especially in firearm owners. This study examines how
      such factors are associated with firearm owners' current firearm storage methods
      and openness to changing storage methods. METHOD: 300 firearm owners completed a
      survey on Amazon's Mechanical Turk program; 176 participants reported being
      exposed to suicide. Perceived closeness was rated as Not at all close, Close, or
      Extremely Close. RESULTS: Those exposed to suicide were more open to secure
      storage and temporarily storing the firearm with a trusted individual to prevent
      someone else's suicide. Those close to the suicide decedent were more likely to
      use secure storage practices, more open to using secure storage methods to
      prevent their own and someone else's suicide, and had a higher degree of storage
      methods in place compared to those not close to the decedent. LIMITATIONS: The
      sample may not be representative of all American firearm owners exposed to
      suicide. CONCLUSIONS: Being close to a suicide decedent may influence firearm
      owners' current storage practices and openness to changing storage methods. Such
      individuals may better relate to the suicide decedent and realize the
      significance of using secure storage methods to prevent suicide.

PMID- 30195233
TI  - The influence of mood and attitudes towards eating on cognitive and
      autobiographical memory flexibility in female university students.
AB  - Cognitive flexibility, as measured through set-shifting ability, appears to be
      impaired in patients with eating disorders (EDs). Thus, it is important to
      determine if the switching deficit seen in clinical eating disorders generalizes
      to participants with a subclinical disordered eating. Another deficit manifested
      by clinical and subclinical disordered eating is the ability to retrieve specific
      autobiographical memories. It is possible that deficits in autobiographical
      memory retrieval extends to the ability to shift between retrieving specific
      versus general autobiographical memory information, a function important for
      problem -solving and emotion regulation. Therefore, the aims of the present study
      were to determine whether deficits in set-shifting are evident in a non-clinical
      sample of female university students with eating concerns, and whether
      inflexibility is also manifested in autobiographical memory retrieval. Sixty-nine
      female undergraduate students completed a measure of autobiographical memory
      flexibility, a set-shifting task (Brixton Spatial Anticipation Test) and measures
      of mood, ruminative thinking, and eating habits. After controlling for mood and
      rumination, bulimic traits predicted set-shifting ability and flexibility in
      autobiographical memory retrieval. Thus, flexibility deficits appear to manifest
      at the subclinical level, are evident in different domains, and appear to be
      related to bulimic traits, such as binge eating.

PMID- 30195234
TI  - Computer-aided identification of natural lead compounds as cyclooxygenase-2
      inhibitors using virtual screening and molecular dynamic simulation.
AB  - In order to find more natural lead-compounds as inhibitors for Cyclooxygenase-2,
      the essential structural features for human cyclooxygenase-2 inhibitors and 3D
      Quantitative structure activity relationship (3D-QSAR) model were carried out
      based on dataset from three confirmatory bioassays using Phase program. Six point
      pharmacophore (AAHRRR) of COX-2 selective inhibitors was generated from training
      set of 52 compounds. The 3D-QSAR model was selected as having favourable
      statistic measures (R2 = 0.93, Q2ext = 0.81) for the training set and test set
      respectively. This model was developed using the best pharmacophore hypothesis
      that helped to reveal the essential features responsible for the anti
      inflammatory activity. As a result, this pharmacophore hypothesis has aided in
      the identification of new four natural lead compounds from UNPD database
      (UNPD100208, UNPD168234, UNPD91145, UNPD57376) that can be used as potential anti
      inflammatory agents or as a core structure to develop other more selective
      molecules. This result was confirmed by molecular docking, which showed that
      these four natural lead-compounds adopt the same orientation as Rofecoxib in the
      COX-2 active site. On the other hand, a molecular dynamic simulation (MDS) was
      applied and repeated on the top ranking complex 5KIR-UNPD100208 and compared with
      the results of MDS of 5KIR-Rofecoxib. The results from MDS revealed a good
      stability of the compound UNPD100208 in the active site based on several
      parameters such as RMSD, RMSF and potential energy, which can nominate it as a
      natural anti-inflammatory lead-compound candidate.

PMID- 30195235
TI  - Flexibility enables to discriminate between ligands: Lessons from structural
      ensembles of Bcl-xl and Mcl-1.
AB  - The proteins of Bcl-2 family, which are promising anti-cancer-drug targets, have
      substantial similarity in primary sequence and share homologous domains as well
      as similar structural folds. In spite of similarities in sequence and structures,
      the members of its pro- and anti- apoptotic subgroups form complexes with
      different type of partners with discriminating binding affinities. Understanding
      the origin of this discrimination is very important for designing ligands that
      can either selectively target a protein or could be made broad ranged as
      necessary. Using principal component analysis (PCA) of the available structures
      and from the analysis of the evolution of the binding pocket residues, the
      correlation has been investigated considering two important anti-apoptotic
      protein Bcl-xl and Mcl-1, which serve as two ideal representatives of this
      family. The flexibility of the receptor enables them to discriminate between the
      ligands or the binding partners. It has been observed that although Bcl-xl and
      Mcl-1 are classified as homologous proteins, through the course of evolution the
      binding pocket residues are highly conserved for Bcl-xl; whereas they have been
      substituted frequently in Mcl-1. The investigation has revealed that the Bcl-xl
      can adjust the backbone conformation of the binding pocket residues to a larger
      extent to complement with the shape of different binding partners whereas the Mcl
      1 shows more variation in the side chain conformation of binding pocket residues
      for the same purpose.

PMID- 30195236
TI  - Drug-Related Morbidity in Brazil: A Cost-of-Illness Model.
AB  - OBJECTIVES: To estimate the proportion of patients with drug-related morbidities
      (DRMs), DRM preventability, and the cost of illness of the DRMs in Brazil.
      METHODS: We used the decision-analytic model initially developed by Johnson and
      Bootman (Drug-related morbidity and mortality. A cost-of-illness model. J Manag
      Care Pharm 1996;2:39-47), which was adapted to the reality of the present study.
      A hypothetical cohort of patients in ambulatory care setting was simulated
      considering the perspective of the Brazilian public health system. Direct costs
      related to health care were obtained from the national databases, and the
      probability of occurrence of DRMs was established by a panel of clinical experts.
      Sensitivity analyses were conducted. RESULTS: An estimated 59% +/- 14% of all
      patients assisted by the health system suffer some DRMs. Given these cases, 53%
      +/- 18% were considered preventable. The average cost of managing a patient with
      any DRM was US $155. The cost of illness of the DRMs in Brazil would account for
      nearly US $18 billion (US $9-$27 billion) (best and worst case scenarium)
      annually. This amount is 5 times higher than what the Ministry of Health spends
      to guarantee free medicines in Brazil. Hospitalizations and long-term stays in
      hospital correspond to 75% of this cost. The sensitivity analysis showed that the
      model is sensitive to variations in these two outcomes. CONCLUSIONS: According to
      the model, a large proportion of patients experience DRM and the economic impact
      to solve these problems is substantial for the health system. Considering that
      more than half of these cases are preventable, it could be possible to achieve an
      enormous saving of resources through actions that improve the process of
      medication use.

PMID- 30195237
TI  - Structure-based design of allosteric calpain-1 inhibitors populating a novel
      bioactivity space.
AB  - Dimeric calpains constitute a promising therapeutic target for many diseases such
      as cardiovascular, neurodegenerative and ischaemic disease. The discovery of
      selective calpain inhibitors, however, has been extremely challenging.
      Previously, allosteric inhibitors of calpains, such as PD150606, which included a
      specific alpha-mercaptoacrylic acid sub-structure, were reported to bind to the
      penta-EF hand calcium binding domain, PEF(S) of calpain. Although these are
      selective to calpains over other cysteine proteases, their mode of action has
      remained elusive due to their ability to inhibit the active site domain with and
      without the presence of PEF(S), with similar potency. These findings have led to
      the question of whether the inhibitory response can be attributed to an
      allosteric mode of action or alternatively to inhibition at the active site. In
      order to address this problem, we report a structure-based virtual screening
      protocol as a novel approach for the discovery of PEF(S) binders that populate a
      novel chemical space. We have identified compound 1, Vidupiprant, which is shown
      to bind to the PEF(S) domain by the TNS displacement method, and it exhibited
      specificity in its allosteric mode of inhibition. Compound 1 inhibited the full
      length calpain-1 complex with a higher potency (IC50 = 7.5 MUM) than the
      selective, cell-permeable non-peptide calpain inhibitor, PD150606 (IC50 = 19.3
      MUM), where the latter also inhibited the active site domain in the absence of
      PEF(S) (IC50 = 17.8 MUM). Hence the method presented here has identified known
      compounds with a novel allosteric mechanism for the inhibition of calpain-1. We
      show for the first time that the inhibition of enzyme activity can be attributed
      to an allosteric mode of action, which may offer improved selectivity and a
      reduced side-effects profile.

PMID- 30195238
TI  - ATP citrate lyase (ACLY) inhibitors: An anti-cancer strategy at the crossroads of
      glucose and lipid metabolism.
AB  - ATP citrate lyase (ACLY) is a cytosolic homotetrameric enzyme that catalyzes the
      conversion of citrate and coenzyme A (CoA) to acetyl-CoA and oxaloacetate, with
      the simultaneous hydrolysis of ATP to ADP and phosphate. Interestingly, ACLY is a
      strategic enzyme linking both the glycolytic and lipidic metabolism. In tumour
      cells characterized by an altered energetic metabolism, an increased glucose
      uptake and an accelerated glycolytic flux lead to an intensified production of
      mitochondrial citrate. Once transported to the cytosol, citrate is here converted
      by ACLY to acetyl-CoA, an essential biosynthetic precursor for fatty acid
      synthesis and mevalonate pathway. ACLY expression and activity proved to be
      aberrantly expressed in many types of tumours, and its pharmacological or genetic
      inhibition significantly inhibited cancer cell proliferation and induced
      apoptosis. Increasing evidences highlight the central role of ACLY, conferring a
      great therapeutic potential to this enzyme as a key target for the treatment of
      cancer. ACLY inhibitors, previously developed for metabolic disorders, have
      recently attracted interest as promising anti-cancer agents. After a brief
      introduction to the structure and the pathophysiological role of ACLY, this
      review article provides an overview of the main ACLY inhibitors reported in the
      literature.

PMID- 30195239
TI  - Chlorambucil-conjugated platinum(IV) prodrugs to treat triple-negative breast
      cancer in vitro and in vivo.
AB  - Modification of platinum (II) into lipophilic platinum (IV) compounds by
      introducing biologically active molecules were widely employed to develop new
      platinum-based prodrugs in the past decade. In this paper, two chlorambucil
      platinum (IV) complexes, CLB-Pt and CLB-Pt-CLB, were synthesized and displayed
      very potent antiproliferative activity against all the tested cancer cell lines,
      such as A549, HeLa and MCF-7, especially to treat the well-known refractory
      triple-negative breast cancer. CLB-Pt-CLB significantly improved cell-killing
      effect in triple-negative subtype MDA-MB-231 cells, and showed much stronger
      cytotoxicity than either monotherapy or combination of cisplatin and
      chlorambucil. CLB-Pt-CLB prodrug entered cells in dramatically increased amount
      compared with cisplatin and enhanced DNA damage, inducing cancer cell apoptosis.
      It exhibited high anticancer activity and no observable toxicity in BALB/c nude
      mice bearing MDA-MB-231 tumors. The chlorambucil moiety not only greatly assisted
      the passive diffusion of CLB-Pt-CLB into cells, but also produced the synergism
      with cisplatin in targeting DNA.

PMID- 30195241
TI  - Changes in supervised drug-injecting practices following a community-based
      educational intervention: A longitudinal analysis.
AB  - BACKGROUND: People who inject drugs face several health issues because of unsafe
      injecting practices. We aimed to evaluate changes in supervised drug-injecting
      practices following the implementation of a face-to-face educational
      intervention. METHODS: The national study ANRS-AERLI was conducted in 17 harm
      reduction (HR) facilities in France between 2011 and 2013. Eight offered the
      intervention and nine did not. We conducted a pre-post analysis focusing on
      injecting practices data, collected in the 8 HR facilities providing the
      intervention. The intervention consisted of providing face-to-face educational
      sessions including direct observation of injecting practices, counseling about
      safer injecting, and shared discussion. Injecting practices were collected
      following a checklist and classified as safe or unsafe. To assess changes in
      injecting practices, practices were compared before (at baseline) and after at
      least one educational session. FINDINGS: Mixed logistic models showed that the 78
      participants included were more likely to improve in the following drug-use
      steps: setting up a clean preparation area (Adjusted Odds Ratio (AOR) = 3.4, 95%
      Confidence Interval (95% CI) = 1.6-7.6), hand washing (AOR = 7.2, 95% CI = 3.1
      16.4), skin cleaning (AOR = 5.6, 95% CI = 2.5-12.1), choice of safe injection
      site (AOR = 6.5, 95% CI = 1.5-28.8) and post-injection bleeding management (AOR =
      12.8, 95% CI = 5.5-29.9). Furthermore, participants were less likely to lick
      their needles before injecting (AOR = 8.1, 95% CI = 1.5-43.4) and to perform
      booting/flushing (AOR = 2.5, 95% CI = 1.2-5.3). CONCLUSIONS: The AERLI
      intervention seems to be effective in increasing safe drug-injecting practices.

PMID- 30195240
TI  - Design, synthesis and pharmacological evaluation of N4,N6-disubstituted
      pyrimidine-4,6-diamine derivatives as potent EGFR inhibitors in non-small cell
      lung cancer.
AB  - A novel series of 4, 6-disubstituted pyrimidines derivatives were designed,
      synthesized, and evaluated as epidermal growth factor receptor (EGFR) inhibitors
      for non-small cell lung cancer(NSCLC). 4, 6-disubstituted pyrimidines as core
      structure was utilized to substitute the lead structure AZD3759 of the
      quinazoline basic skeleton via an approach involving scaffold hopping. It was
      found that compound Yfq07 exhibited the best inhibitory effect compared with
      AZD3759 in vitro and in vivo: Yfq07 exhibited a competitive ATP inhibitory
      effect, multiple target effects, and further featured a stronger activity against
      H3255, A431, HCC827, PC-9 and H1975 compared to AZD3759. Moreover, a stronger pro
      apoptotic effect, inhibition of cell G2/M phase on A431, H3255, HCC827 and H1975
      could also be observed. In this study, the ultimate goal was changing the core
      structure to improve other epidermal growth factor receptor tyrosine kinase
      inhibitors (EGFR-TKIs) properties while retaining the overall potency. Yfq07 was
      further explored as an effective 4, 6-pyrimidine anticancer agent for the
      treatment of human NSCLC.

PMID- 30195242
TI  - The importance of considering polysubstance use: lessons from cocaine research.
AB  - BACKGROUND: Polysubstance use (PSU) is prevalent among individuals with substance
      use disorders, but the vast majority of preclinical substance use research has
      focused on individual substances in isolation. Cocaine has been prevalent in the
      repertoire of persons who use more than one illicit substance. METHODS: We
      conducted a meta-analysis combining results from literature searches and
      secondary data analyses to estimate the prevalence of simultaneous and concurrent
      cocaine + alcohol and cocaine + cannabis use among cocaine users. We next
      summarized the small body of literature on behavioral, cognitive and
      neurobiological consequences of cocaine PSU across species, with a focus on
      alcohol and cannabis. Finally, we used systematic literature searches to assess
      the extent to which human and animal studies on the neurobiological consequences
      of cocaine include PSU subjects. RESULTS: The estimated prevalence of
      simultaneous and concurrent alcohol use among human cocaine users was 74% and
      77%, respectively. The estimated prevalence of simultaneous and concurrent
      cannabis use among cocaine users was 38% and 64%, respectively. Consumption of
      alcohol or cannabis with cocaine enhances subjective responses to cocaine,
      concomitant with changes in cocaine metabolism that increase blood cocaine
      levels, and, in the case of alcohol, produce the psychoactive metabolite
      cocaethylene. There is also consistent evidence for neurobiological effects of
      cocaine + alcohol combinations. However, animal PSU research with cocaine lags
      behind human research. CONCLUSION: Based on the prevalence and known consequences
      of PSU, consideration of PSU in both human and animal research is vital for
      understanding patterns of substance use.

PMID- 30195245
TI  - Dietary carbohydrate quality and quantity in relation to the incidence of type 2
      diabetes: A prospective cohort study of middle-aged and older Korean adults.
AB  - OBJECTIVES: This study aimed to investigate whether dietary glycemic load (GL),
      glycemic index (GI), and carbohydrate intake were prospectively associated with
      incident type 2 diabetes mellitus (T2DM) in a middle-aged and older Korean
      populations. METHODS: Data from the Korean Genome and Epidemiology Study were
      used. A total of 7294 Korean adults ages 40 y to 69 y and with no previous
      diagnosis of T2DM or cancer at baseline were followed for 10 y. Dietary GL, GI,
      and carbohydrate intake were estimated on the basis of participants' responses to
      a validated, semiquantitative, food-frequency questionnaire at baseline. T2DM was
      defined according to the World Health Organization and International Diabetes
      Federation criteria. RESULTS: During 7.7 y (56 377 person-years) of follow-up
      time, 1259 participants (17.3%) developed T2DM. Grain and its products
      (particularly refined and whole grains) were the greatest contributors to dietary
      GL. In the multivariable Cox models, dietary GL was differentially associated
      with T2DM risk by sex. Men in the highest quintile demonstrated a higher risk of
      T2DM incidence than did those with the lowest, energy-adjusted, dietary GL
      (hazard ratio for fifth vs. first quarter = 1.26; 95% confidence interval, 1.05
      1.52; P for trend < 0.05) but no association between dietary GL and the risk of
      T2DM was observed in women. Similar to the findings from the main models, the
      effect of dietary GL on T2DM incidence according to body mass index, abdominal
      obesity, and physical activity levels differed substantially by sex. CONCLUSIONS:
      High GL diets may increase the risk of the development of T2DM in middle-aged and
      older Korean men but not in women. Nutrition education and emphasis on self
      monitoring of dietary carbohydrate quality and quantity of overall diets is
      necessary in the middle-aged and older Korean populations.

PMID- 30195244
TI  - Randomized open-label trial of docosahexaenoic acid-enriched fish oil and fish
      meal on cognitive and behavioral functioning in Omani children.
AB  - OBJECTIVE: This study aimed to examine the effect of docosahexaenoic acid (DHA)
      enriched fish oil supplement and meal of grilled fish on cognitive and behavioral
      functioning manifested as attention-deficit/hyperactivity disorder in primary
      school students 9 to 10 y of age in Muscat, Oman. METHODS: This randomized open
      label trial involved two types of interventions: fish oil supplement or one
      serving (100 g) of grilled fish per day (Sunday through Friday) for 12 weeks. Red
      cell total lipid DHA levels were assessed. The Verbal Fluency Test, Buschke
      Selective Reminding Test, and Trail Making Test were used to measure cognitive
      functioning. Behavioral functioning was assessed using a standardized Arabic
      version of the National Initiative for Children's Health Quality Vanderbilt
      Assessment Scales. All measurements were carried out before and after
      intervention. RESULTS: DHA levels increased by 72% and 64% in the fish oil (mean,
      3.6%-6.2%) and fish-meal (mean, 3.4%-5.6%) groups, respectively (P = 0.000). The
      Trail Making Test was the only cognitive test that demonstrated marked
      differences between groups: Median interquartile range difference between pre-
      and postintervention in the Trail Making Part B score was 61.5 (SE, 19.3, 103.2)
      in the fish oil versus fish-meal group, 24.5 (SE, -15.2, 74.7, P = 0.005). The
      Vanderbilt Assessment Scales also showed significant differences between groups
      (P < 0.001). CONCLUSION: This study contributed to available evidence on the
      cognitive and behavioral benefits of DHA in healthy school children. Expanding
      the food fortification program with DHA-enriched fish oil should be considered as
      part of broader policy to improve child health.

PMID- 30195243
TI  - Randomized controlled trial of a positive affect intervention for methamphetamine
      users.
AB  - BACKGROUND: Contingency management (CM) is an evidence-based intervention
      providing rewards in exchange for biomarkers that confirm abstinence from
      stimulants such as methamphetamine. We tested the efficacy of a positive affect
      intervention designed to boost the effectiveness of CM with HIV-positive,
      methamphetamine-using sexual minority men. METHODS: This attention-matched,
      randomized controlled trial of a positive affect intervention delivered during CM
      was registered on www.clinicaltrials.gov (NCT01926184). In total, 110 HIV
      positive sexual minority men with biologically confirmed, recent methamphetamine
      use were enrolled. Five individual sessions of a positive affect intervention (n
      = 55) or an attention-control condition (n = 55) were delivered during three
      months of CM. Secondary outcomes examined over the 3-month intervention period
      included: 1) psychological processes relevant to affect regulation (i.e.,
      positive affect, negative affect, and mindfulness); 2) methamphetamine craving;
      3) self-reported stimulant use (past 3 months); and 4) cumulative number of urine
      samples that were non-reactive for stimulants (i.e., methamphetamine and cocaine)
      during CM. RESULTS: Those randomized to the positive affect intervention reported
      significant increases in positive affect during individual sessions and increases
      in mindfulness over the 3-month intervention period. Intervention-related
      improvements in these psychological processes relevant to affect regulation were
      paralleled by concurrent decreases in methamphetamine craving and self-reported
      stimulant use over the 3-month intervention period. CONCLUSIONS: Delivering a
      positive affect intervention may improve affect regulation as well as reduce
      methamphetamine craving and stimulant use during CM with HIV-positive,
      methamphetamine-using sexual minority men.

PMID- 30195246
TI  - Relative validity of a web-based, self-administered, 24-h dietary recall to
      evaluate adherence to Canadian dietary guidelines.
AB  - OBJECTIVES: A new, web-based, 24-h recall (R24 W) was developed and programmed to
      assess adherence to Canadian dietary guidelines by automatically generating the
      Canadian Healthy Eating Index 2007 (C-HEI 2007). The aim of the present study was
      to determine the relative validity of the R24 W in terms of its ability to
      generate C-HEI 2007 scores that match those derived from a food record (FR).
      METHODS: A total of 57 women and 50 men filled a 3-d FR and three 24-h food
      recalls with the R24 W. C-HEI 2007 was calculated with both dietary assessment
      tools and compared using de-attenuated correlations and kappa scores. Internal
      validity (correlations between total score and components) and external validity
      (comparison of the C-HEI 2007 by sex and age groups) were compared between the
      two dietary assessment methods. RESULTS: The average C-HEI 2007 score obtained
      with the R24 W (59.4 +/- 11.8) was significantly lower than the one obtained with
      the FR (62.6 +/- 11.1). However, the de-attenuated correlation coefficient
      between C-HEI 2007 obtained either with R24 W or FR was 0.80 (P < 0.01) and 91.6%
      of participants were classified in the same or adjacent quartile of C-HEI 2007
      with both tools. Women obtained a higher C-HEI 2007 mean score (P < 0.01) with
      both methods and older adults (age: >51 y) received a higher score than younger
      adults (age: 18-30 y; P < 0.01) with the R24 W but not with the FR (P = 0.22).
      CONCLUSIONS: Although the R24 W yields lower C-HEI 2007 scores compared with data
      from FR, the classification of individuals was highly consistent between the two
      measurements.

PMID- 30195247
TI  - The magnitude and impact of tobacco marketing exposure in adolescents' day-to-day
      lives: An ecological momentary assessment (EMA) study.
AB  - PURPOSE: Research indicates that tobacco marketing contributes to higher pro
      tobacco attitudes and behaviors among adolescents, but no studies have been able
      to assess the impact of real-world tobacco marketing exposures in real-time. The
      purpose of this study was to examine the magnitude and impact of tobacco
      marketing exposure on adolescents using ecological momentary assessment (EMA).
      Our primary hypotheses were that (1) youth would most frequently report tobacco
      marketing at the retail points-of-sale and (2) greater exposures to tobacco
      marketing would be associated with more favorable tobacco-related attitudes, use,
      and expectancies. METHODS: Participants were adolescent males from rural and
      urban Ohio (N = 176, ages 11-16). For ten days, these adolescents were prompted
      at two-three random times/day to complete a brief smartphone-based survey about
      their exposures and responses to tobacco-related advertising. RESULTS:
      Adolescents reported exposures to tobacco marketing an average of 1.9 times over
      the 10-day EMA period, with over 10% seeing a tobacco advertisement 5 or more
      times. Reports of marketing exposures occurred most frequently at the point-of
      sale; exposures were higher among tobacco users and rural adolescents. Consistent
      with hypotheses, marketing exposure was related to more positive attitudes to the
      tobacco advertisements, more tobacco use, and higher expectancies to use in the
      future. CONCLUSIONS: Overall, these findings signal the magnitude of tobacco
      marketing exposures and their pernicious impact on youth. Findings underscore the
      importance of federal, state, and local-level tobacco regulatory policies to
      protect youth from the marketing that puts them at risk for a lifetime of
      nicotine addiction and tobacco-related diseases.

PMID- 30195248
TI  - Analysis and correction of errors in DTI-based tractography due to diffusion
      gradient inhomogeneity.
AB  - The DTI-based tractography, despite its restrictions, is the most widely utilized
      fiber tracking method in clinical practice. Its fidelity is strictly dependent on
      the precision and accuracy of the DTI measurement, which in turn is limited by
      the linearity of the diffusion sensitizing gradient. The influence of the
      gradient distortions on the differences between the real and measured orientation
      of fibers was investigated by computer simulations. In addition, the potential of
      the b-matrix Spatial Distribution in DTI (BSD-DTI) technique in correcting such
      kind of errors was demonstrated experimentally. The simulations revealed that the
      diffusion gradient inhomogeneity, if not corrected, leads to the erroneous
      indication of the fiber direction. The average and maximum deviations were about
      1 degrees  and 15 degrees , respectively. Remarkably, the deviation between the
      real and measured orientation of fibers is directionally dependent, what was
      confirmed in MRI measurement. The deviation errors can be effectively corrected
      by preceding the DTI measurement with the BSD-DTI calibration.

PMID- 30195249
TI  - Helix-loop-helix peptide foldamers and their use in the construction of hydrolase
      mimetics.
AB  - De novo designed helix-loop-helix peptide foldamers containing cis-2
      aminocyclopentanecarboxylic acid residues were evaluated for their conformational
      stability and possible use in enzyme mimetic development. The correlation between
      hydrogen bond network size and conformational stability was demonstrated through
      CD and NMR spectroscopies. Molecules incorporating a Cys/His/Glu triad exhibited
      enzyme-like hydrolytic activity.

PMID- 30195250
TI  - Expression and antiviral function of ARGONAUTE 2 in Nicotiana benthamiana plants
      infected with two isolates of tomato ringspot virus with varying degrees of
      virulence.
AB  - ARGONAUTEs (notably AGO1 and AGO2) are effectors of plant antiviral RNA
      silencing. AGO1 was shown to be required for the temperature-dependent symptom
      recovery of Nicotiana benthamiana plants infected with tomato ringspot virus
      (isolate ToRSV-Rasp1) at 27  degrees C. In this study, we show that symptom
      recovery from isolate ToRSV-GYV shares similar hallmarks of antiviral RNA
      silencing but occurs at a wider range of temperatures (21-27  degrees C). At 21 
      degrees C, an early spike in AGO2 mRNAs accumulation was observed in plants
      infected with either ToRSV-Rasp1 or ToRSV-GYV but the AGO2 protein was only
      consistently detected in ToRSV-GYV infected plants. Symptom recovery from ToRSV
      GYV at 21  degrees C was not prevented in an ago2 mutant or by silencing of AGO1
      or AGO2. We conclude that other factors (possibly other AGOs) contribute to
      symptom recovery under these conditions. The results also highlight distinct
      expression patterns of AGO2 in response to ToRSV isolates and environmental
      conditions.

PMID- 30195251
TI  - Impaired heterologous protein-protein interaction is an essential cause for non
      viability of WNV/DENV recombinants.
AB  - Flavivirus RNA replication starts at 3'-end, where it folds into a highly
      conserved stem-loop structure. We attempted to identify the viral non-structural
      proteins (NSPs) that might specifically interact with the 3'-stemloop (3'SL)
      through a genetic approach. WNV/DENV2 chimeric recombinants that contain Dengue2
      (DENV2) gene(s) in West Nile virus (WNV) backbone were tested for replication
      competence. Three of seven recombinant viruses, containing the DENV2 NS1, NS2A,
      or NS4B gene and terminated with a mutated 3'SL (MutC 3'SL), were viable. Of
      these three, only those bearing the DENV2 NS1 and NS2A substitutions remained
      infectious when the MutC 3'SL was replaced by the wildtype WNV 3'SL. However,
      none of the seven chimeric recombinants bearing the DENV2 3'SL were viable. We
      then investigated the causes for failed replication of WNV/DENV2 chimeric
      recombinants. Proteolytic cleavage of NS polyproteins was defective by
      heterologous protease NS2B/3, but was efficient by homologous DENV2 NS2B/3
      protease. Whereas, the heterologous polyproteins that contained DENV2 homologous
      protease were found to produce abnormal vesicles. WNV/DENV2 recombinants
      expressing the DENV2 homologous protease did not produce infectious virus either.
      We examined NS protein-protein interaction (PPI) and found that heterologous PPI
      (hPPI) between WNV and DENV2 NSPs were impaired to various degrees. Insufficient
      PPIs occurred mainly between heterologous NS2B and NS3; NS2B and NS4A; NS3 and
      NS5, correlating to those non-viability of substitution mutants. Our results
      indicate that impaired PPI may decrease protease activity and affect vesicle
      formation, and is the essential cause for non-viability of the WNV/DENV2
      recombinants.

PMID- 30195252
TI  - Integration of two herbivore-induced plant volatiles results in synergistic
      effects on plant defence and resistance.
AB  - Plants can use induced volatiles to detect herbivore- and pathogen-attacked
      neighbors and prime their defenses. Several individual volatile priming cues have
      been identified, but whether plants are able to integrate multiple cues from
      stress-related volatile blends remains poorly understood. Here, we investigated
      how maize plants respond to two herbivore-induced volatile priming cues with
      complementary information content, the green leaf volatile (Z)-3-hexenyl acetate
      (HAC) and the aromatic volatile indole. In the absence of herbivory, HAC directly
      induced defence gene expression, whereas indole had no effect. Upon induction by
      simulated herbivory, both volatiles increased jasmonate signalling, defence gene
      expression, and defensive secondary metabolite production and increased plant
      resistance. Plant resistance to caterpillars was more strongly induced in dual
      volatile-exposed plants than plants exposed to single volatiles.. Induced defence
      levels in dual volatile-exposed plants were significantly higher than predicted
      from the added effects of the individual volatiles, with the exception of induced
      plant volatile production, which showed no increase upon dual-exposure relative
      to single exposure. Thus, plants can integrate different volatile cues into
      strong and specific responses that promote herbivore defence induction and
      resistance. Integrating multiple volatiles may be beneficial, as volatile blends
      are more reliable indicators of future stress than single cues.

PMID- 30195253
TI  - Helianthus annuus L. flower prevents UVB-induced photodamage in human dermal
      fibroblasts by regulating the MAPK/AP-1, NFAT, and Nrf2 signaling pathways.
AB  - BACKGROUND: Excessive ultraviolet radiation usually causes skin photoaging,
      inflammation, and even photocarcinogenesis. UV radiation-generated reactive
      oxygen species (ROS) are a major contributing factor to photodamage. The flowers
      of Helianthus annuus L. have been reported to possess strong anti-inflammatory
      and antioxidant activity. However, there are few reports on the use of H. annuus
      L. to relieve UVB-induced photoaging. PURPOSE: In this study, we evaluated the
      protective effect of a 50% ethanol extract of H. annuus L. flower (HAF) against
      UVB-induced photodamage using normal human dermal fibroblasts. METHODS: The
      secretion of ROS, interleukin-6 (IL-6), vascular endothelial growth factor
      (VEGF), matrix metalloproteinases (MMPs), procollagen type I, and transforming
      growth factor-beta1 (TGF-beta1) was measured with kits. The messenger RNA levels
      of COX-2, iNOS, and TGF-alpha were measured by RT-PCR. The AP-1, MAPK, NFAT, and
      Nrf2 pathways were investigated by Western blot analysis. RESULTS: HAF extract
      significantly blocked UVB-induced ROS and MMP (MMP-1 and MMP-3) production and
      procollagen type I reduction. Further study demonstrated that the photoaging
      inhibitory actions were related to promotion of Nrf2 nuclear translocation,
      upregulation of TGF-beta1 level, and downregulation of AP-1 and MAPK
      phosphorylation. Importantly, HAF effectively inhibited UVB-induced VEGF and
      inflammatory cytokines such as IL-6, COX-2, iNOS, and TNF-alpha secretion, which
      might be involved in the regulation of the NFAT signaling pathway. CONCLUSION:
      Our results indicate that HAF is a useful botanical source protecting against UVB
      mediated skin photodamage.

PMID- 30195254
TI  - Geleophysic dysplasia: 48 year clinical update with emphasis on cardiac care.
AB  - Geleophysic dysplasia is a rare skeletal dysplasia often complicated by
      progressive cardiac disease. Information about long-term outcomes is limited. A
      clinical update of the oldest surviving patient described with geleophysic
      dysplasia type 1 is provided. Special note is made in relation to the cardiac
      disease and interventions. Genetic testing of ADAMTSL2 revealed a previously
      reported missense mutation as well as a novel nonsense mutation, which can be
      added to the list of causative mutations in geleophysic dysplasia.

PMID- 30195255
TI  - Exposure to household air pollution from biomass cookstoves and blood pressure
      among women in rural Honduras: A cross-sectional study.
AB  - Growing evidence links household air pollution exposure from biomass cookstoves
      with elevated blood pressure. We assessed cross-sectional associations of 24-hour
      mean concentrations of personal and kitchen fine particulate matter (PM2.5 ),
      black carbon (BC), and stove type with blood pressure, adjusting for confounders,
      among 147 women using traditional or cleaner-burning Justa stoves in Honduras. We
      investigated effect modification by age and body mass index. Traditional stove
      users had mean (standard deviation) personal and kitchen 24-hour PM2.5
      concentrations of 126 MUg/m3 (77) and 360 MUg/m3 (374), while Justa stove users'
      exposures were 66 MUg/m3 (38) and 137 MUg/m3 (194), respectively. BC
      concentrations were similarly lower among Justa stove users. Adjusted mean
      systolic blood pressure was 2.5 mm Hg higher (95% CI, 0.7-4.3) per unit increase
      in natural log-transformed kitchen PM2.5 concentration; results were stronger
      among women of 40 years or older (5.2 mm Hg increase, 95% CI, 2.3-8.1). Adjusted
      odds of borderline high and high blood pressure (categorized) were also elevated
      (odds ratio = 1.5, 95% CI, 1.0-2.3). Some results included null values and are
      suggestive. Results suggest that reduced household air pollution, even when
      concentrations exceed air quality guidelines, may help lower cardiovascular
      disease risk, particularly among older subgroups.

PMID- 30195256
TI  - An evolutionary theory of behavior dynamics applied to concurrent ratio
      schedules.
AB  - An evolutionary theory of adaptive behavior dynamics was tested by studying the
      behavior of artificial organisms (AOs) animated by the theory, working on
      concurrent ratio schedules with unequal and equal ratios in the components. The
      evolutionary theory implements Darwinian rules of selection, reproduction, and
      mutation in the form of a genetic algorithm that causes a population of potential
      behaviors to evolve under the selection pressure of consequences from the
      environment. On concurrent ratio schedules with unequal ratios in the components,
      the AOs tended to respond exclusively on the component with the smaller ratio,
      provided that ratio was not too large and the difference between the ratios was
      not too small. On concurrent ratio schedules with equal ratios in the components,
      the AOs tended to respond exclusively on one component, provided the equal ratios
      were not too large. In addition, the AOs' preference on the latter schedules
      adjusted rapidly when the equal ratios were changed between conditions, but their
      steady-state preference was a continuous function of the value of the equal
      ratios. Most of these outcomes are consistent with the results of experiments
      with live organisms, and consequently support the evolutionary theory.

PMID- 30195257
TI  - The role of hybridization and introgression in maintaining species integrity and
      cohesion in naturally isolated inselberg bromeliad populations.
AB  - Hybridization is a widespread phenomenon present in numerous lineages across the
      tree of life. Its evolutionary consequences range from effects on the origin and
      maintenance, to the loss of biodiversity. We studied genetic diversity and intra-
      and interspecific gene flow between two sympatric populations of closely-related
      species, Pitcairnia flammea and P. corcovadensis (Bromeliaceae), which are
      adapted to naturally fragmented Neotropical inselbergs, based on nuclear and
      plastidial DNA. Our main results indicate a strong reproductive isolation
      barrier, although low levels of interspecific gene flow were observed in both
      sympatric populations. The low rates of intraspecific gene flow observed for both
      P. corcovadensis and P. flammea populations corroborate the increasing body of
      evidence that inselberg bromeliad species are maintained as discrete evolutionary
      units despite the presence of low genetic connectivity. Nuclear patterns of
      genetic diversity and gene flow revealed that hybridization and introgression
      might not cause species extinction via genetic assimilation of the rare P.
      corcovadensis. In the face of reduced intraspecific gene exchange, hybridization
      and introgression may be important aspects of the Pitcairnia diversification
      process, with a positive evolutionary impact at the bromeliad community level,
      and thus contribute to increasing and maintaining genetic diversity in local
      isolated inselberg populations.

PMID- 30195258
TI  - The influence of drug properties and host factors on delayed onset of symptoms in
      drug-induced liver injury.
AB  - BACKGROUND & AIMS: Most patients with drug-induced liver injury (DILI) manifest
      clinical symptoms while on therapy, while some patients manifest days or weeks
      after drug cessation (delayed onset). This challenges DILI causality assessment
      and diagnosis. Factors contributing to the delayed onset phenotype are currently
      unknown. We explored factors contributing to delayed onset of DILI by analysing
      culprit drug properties, host factors and their interactions in a large patient
      population from the Spanish DILI Registry. METHODS: Clinical information from 388
      patients (69 presented delayed onset) and drug properties of 43 causative drugs
      (45 active ingredients) were analysed. A two-tier regression-based model was used
      to assess host/drug interactions affecting the probability of delayed onset.
      RESULTS: Antibacterial and anti-inflammatory drugs accounted for the delayed
      onset cases. Drug property of <50% hepatic metabolism (odds ratio [OR] 11.06, 95%
      confidence interval [95% CI]: 4.4-32.2, P = 0.0003), daily dose >=1000 mg (OR:
      2.77, 95% CI: 1.3-6.1, P = 0.0063) and the absence of pre-existing conditions in
      a patient (OR: 2.55, 95% CI: 1.3-4.9, P = 0.0043) were independently associated
      with delayed onset. The findings were consistent when externally validated using
      Latin American DILI Network cases (N = 131). Likewise, drug properties of
      mitochondrial liability and Pauling electronegativity were associated with
      delayed onset, but dependent on specific host factors such as age, sex and pre
      existing cardiac diseases. CONCLUSIONS: This study demonstrated that delayed
      onset, a specific DILI phenotype, is explained by complex interactions among drug
      properties and host factors and provided mechanistic hypotheses for future
      studies. These findings can help improve the diagnostic capability and causality
      assessment.

PMID- 30195259
TI  - Topical ingenol mebutate for viral wart on the ear.

PMID- 30195260
TI  - An autologous protein gel for soft tissue augmentation: in vitro characterization
      and clinical evaluation.
AB  - BACKGROUND: The aging process affects all organs of the body, but the skin is the
      most visible indicator with a great psychosocial impact. As a consequence, many
      skin anti-aging strategies have been developed to minimize, postpone, and even
      reverse the aging process. Growth factors have been widely studied in skin wound
      healing as these polypeptides play an essential role in the complex process of
      tissue regeneration. Recently, a novel 3D injectable gel based on the autologous
      technology platelet rich in growth factor has been described. OBJECTIVES: In this
      study, a comparison between hyaluronic acid (HA, the gold standard for skin
      rejuvenation), and this novel autologous formulation has been conducted. METHODS:
      Rheological and mechanical properties were determined. The in vitro biological
      capacity of both treatments on human dermal fibroblasts proliferation, migration,
      chemotaxis, and extracellular matrix synthesis was also assessed. Additionally, a
      clinical evaluation of the autologous platelet gel treatment was performed by
      macrophotographs, ultrasound analyses, and clinical and patient surveys. RESULTS:
      The autologous gel outperformed the general biomechanical properties of HA and
      kept an optimal viscoelastic gel-like behavior for soft tissue augmentation. Both
      formulations stimulated cell chemotaxis, migration, and type I collagen
      synthesis. The autologous gel induced a statistically higher cell proliferation.
      After the autologous formulation treatment, a soft tissue augmentation effect was
      also noticed along with an overall skin quality improvement in terms of
      hydration, elasticity, wrinkle reduction, and general satisfaction scores.
      CONCLUSIONS: This novel injectable formulation has desirable mechanical and
      bioactive properties for 3D tissue regeneration and might offer a safe and
      effective treatment for depressed areas of the skin.

PMID- 30195261
TI  - How to reprogram microglia toward beneficial functions.
AB  - Microglia, brain cells of nonneural origin, orchestrate the inflammatory response
      to diverse insults, including hypoxia/ischemia or maternal/fetal infection in the
      perinatal brain. Experimental studies have demonstrated the capacity of microglia
      to recognize pathogens or damaged cells activating a cytotoxic response that can
      exacerbate brain damage. However, microglia display an enormous plasticity in
      their responses to injury and may also promote resolution stages of inflammation
      and tissue regeneration. Despite the critical role of microglia in brain
      pathologies, the cellular mechanisms that govern the diverse phenotypes of
      microglia are just beginning to be defined. Here we review emerging strategies to
      drive microglia toward beneficial functions, selectively reporting the studies
      which provide insights into molecular mechanisms underlying the phenotypic
      switch. A variety of approaches have been proposed which rely on microglia
      treatment with pharmacological agents, cytokines, lipid messengers, or microRNAs,
      as well on nutritional approaches or therapies with immunomodulatory cells.
      Analysis of the molecular mechanisms relevant for microglia reprogramming toward
      pro-regenerative functions points to a central role of energy metabolism in
      shaping microglial functions. Manipulation of metabolic pathways may thus provide
      new therapeutic opportunities to prevent the deleterious effects of inflammatory
      microglia and to control excessive inflammation in brain disorders.

PMID- 30195262
TI  - Cellular Response to 3-D Printed Bioactive Silicate and Borosilicate Glass
      Scaffolds.
AB  - The repair and regeneration of loaded segmental bone defects is a challenge for
      both materials and biomedical science communities. Our recent work demonstrated
      the capability of bioactive glass in supporting bone healing and defect bridging
      using a rabbit femur segmental defect model without growth factors or bone marrow
      stromal cells (BMSCs). Here in the current work, a comprehensive in vitro
      evaluation of bioactive silicate (13-93) and borosilicate (2B6Sr) glass scaffolds
      was conducted to provide further understanding of their biological performances
      and to establish a correlation between in vitro and in vivo behaviors. Our in
      vitro evaluation using a murine MC3T3-E1 cell line confirmed the capability of
      both scaffolds to support cell attachment, vascular endothelial growth factor
      (VEGF) formation, and to stimulate mineral deposition and osteoblast marker gene
      expression. In particular, borosilicate (2B6Sr) glass showed a better capability
      in supporting the mineralization and gene expression than silicate (13-93) glass,
      consistent with a faster bone healing ability in vivo. The current in vitro
      results, combined with our previous in vivo findings, provide a strong basis for
      the further translational evaluation of bioactive glass scaffolds and for
      potential preclinical practice. (c) 2018 Wiley Periodicals, Inc. J. Biomed.
      Mater. Res. Part B, 2018.

PMID- 30195263
TI  - Ultra-acceleration of Photochemical Cytosine Deamination by Using a 5'-Phosphate
      Substituted Oligodeoxyribonucleotide Probe Containing a 3-Cyanovinylcarbazole
      Nucleotide at Its 5'-End.
AB  - Genes are the blueprints for the architectures of living organisms, providing the
      backbone of the information required for formation of proteins. Changes in genes
      lead to disorders, and these disorders could be rectified by reversing the
      mutations that caused them. Photochemical methods currently in use for site
      directed mutagenesis employ the photoactive 3-cyanovinylcarbazole (CNV K)
      nucleotide incorporated in the oligodeoxyribonucleotide (ODN) backbone. The major
      drawback of this method, the requirement for high temperature, has been
      addressed, and deamination has previously been achieved at 37  degrees C but with
      low efficiency. Here, efficient deamination has been accomplished under
      physiological conditions by using a short complementary photoactive ODN with a 5'
      phosphate group in the -1 position with respect to the target cytosine. It is
      hypothesized that the free phosphate group affects the microenvironment around
      the target cytosine by activating the incoming nucleophile through hydrogen
      bonding with the water molecule, thus facilitating nucleophilic attack on the
      cytosine C-4 carbon. The degree of deamination observed in this technique is high
      and the effect of the phosphate group is to accelerate the deamination reaction.

PMID- 30195264
TI  - Multidrug-resistant transporter expression does not always result in drug
      resistance.

PMID- 30195265
TI  - The use of cytopathology to identify disturbances in oral squamous cell carcinoma
      at early stage: A case report.
AB  - Early detection of oral squamous cell carcinoma (OSCC) is a challenge for oral
      surgeons, as clinical features are not always classical. Cytopathological assays
      can help identify alterations at the cellular level. This article reports a case
      of OSCC in a young male adult without exposure to classical risk factors. The
      histopathological examination showed a micro invasive carcinoma invading the
      connective tissue. Cytopathological results showed a higher percentage of cells
      in deeper epithelial layers; the cytomorphometric examination revealed a
      nuclear/cytoplasmic ratio of 0.14; the mean number of Nucleolar Organiser Regions
      which have a high affinity for silver (AgNOR) per nucleus was 2.86, and the mean
      percentage of nuclei with >2 AgNOR was 58%. The micronucleus test found 3
      micronucleated cells and several metanuclear aberrations. These findings support
      the hypothesis that cytological examination is an important tool to identify
      early changes in oral smears and thus help in the early clinical detection of
      suspicious malignant oral lesions that should be more rigorously followed.

PMID- 30195266
TI  - Committee II: Guidelines for cytologic sampling techniques of lung and
      mediastinal lymph nodes.
AB  - The Papanicolaou Society of Cytopathology has developed a set of guidelines for
      pulmonary cytology including indications for bronchial brushings, washings, and
      endobronchial ultrasound guided transbronchial fine-needle aspiration (EBUS
      TBNA), technical recommendations for cytological sampling, recommended
      terminology and classification schemes, recommendations for ancillary testing and
      recommendations for post-cytological management and follow-up. All
      recommendations are based on the expertise of the authors, an extensive
      literature review and feedback from presentations at national and international
      conferences. This document selectively presents the results of these discussions.
      The present document summarizes recommendations regarding techniques used to
      obtain cytological and small histologic specimens from the lung and mediastinal
      lymph nodes including rapid on-site evaluation (ROSE), and the triage of
      specimens for immunocytochemical and molecular studies.

PMID- 30195268
TI  - Papilla reconstruction: Interdisciplinary consideration for clinical success.
AB  - : One of the most difficult achievements in the periodontal therapy is the
      reconstruction of interdental papilla that has been lost by periodontal disease.
      The poor esthetic appearance caused by the "black triangle," especially in the
      maxillary anterior region has been a concern for both patients and professionals.
      However, when the papilla destruction is followed by loss of contact point, the
      use of different specialties is usually necessary to restore the interproximal
      embrasure. This clinical case report describes an interdisciplinary (periodontic
      orthodontic-restorative) approach for the treatment of a patient with severe case
      of papilla destruction in an esthetic zone. The patient's esthetic expectations
      for the anterior maxilla were met through phase I treatment, including the
      surgical reconstruction of the papillary complex and the orthodontic movement to
      restore the contact point. However, after the initial treatment was successfully
      concluded, the long-term stability of the result was compromised as the
      intercommunication among the specialists was not coordinated. CLINICAL
      SIGNIFICANCE: The treatment plan that involves interdisciplinary teamwork should
      be followed by an understanding about the principles of the specialties as well
      the intercommunication among specialists.

PMID- 30195267
TI  - Tolerability and efficacy of a medical device repairing emollient cream in adults
      with chronic hand dermatitis.
AB  - BACKGROUND: Emollients are recommended for managing chronic hand dermatitis
      (CHD). Medical device repairing emollient creams (MDRECs) are suitable for
      treating CHD-associated skin lesions, unlike most cosmetic emollient products
      that can only be used on healthy skin. OBJECTIVES: The aim of this study was to
      examine the tolerability and benefit of a MDREC, Dexyane MeD(r) , in adults with
      CHD. METHODS: In an open-label study, adults aged 18-65 years with mild-to
      moderate CHD were instructed to apply the MDREC on both hands twice daily for 3
      weeks. Investigators assessed tolerability and CHD severity on days 1, 8, and 22.
      Subjects assessed CHD severity weekly and completed the Dermatology Life Quality
      Index on days 1, 8, and 22. Differences from baseline were compared by Wilcoxon
      matched-pairs signed-rank test or paired t test. Satisfaction with the MDREC was
      assessed by subjects. RESULTS: Forty subjects were included and completed the
      study. Tolerability was good to excellent for all subjects. Subjects and
      investigators reported decreased severity of CHD at days 8 and 22 compared with
      Day 1 (P < 0.001), and subjects reported decreased pain and pruritus (P < 0.001).
      Quality of life improved, and most subjects were satisfied with the MDREC's
      characteristics and application. CONCLUSIONS: The MDREC was well tolerated and
      may help manage mild-to-moderate CHD.

PMID- 30195269
TI  - Spinal manifestations in 12 patients with musculocontractural Ehlers-Danlos
      syndrome caused by CHST14/D4ST1 deficiency (mcEDS-CHST14).
AB  - Musculocontractural Ehlers-Danlos syndrome caused by mutations in CHST14 (mcEDS
      CHST14) is a recently delineated disorder, characterized by craniofacial,
      skeletal, visceral, and ocular malformations; and progressive cutaneous,
      skeletal, vascular, and visceral fragility-related manifestations. Spinal
      lesions, though one of the most serious complications, have not been investigated
      systematically. In this study, we report detailed and comprehensive information
      about spinal lesions of 12 patients with a mean age at the first visit of 13.4
      years. Eight patients (66.7%) had scoliosis with a Cobb angle >=10 degrees ,
      including one with severe scoliosis with a Cobb angle >=45 degrees . Five
      patients (41.7%) had kyphosis at the thoracolumbar junction with a kyphotic angle
      >=20 degrees . Three patients (25%) developed severe thoracolumbar kyphosis with
      a kyphotic angle >=50 degrees  accompanied by thoracic lordosis with a wedge-like
      vertebral deformity and anterior vertebral osteophyte at the thoracolumbar
      junction, and two of them underwent surgical correction: complicated by fistula
      formation in one and performed safely and effectively through two-staged
      operation in the other. Six patients (50.0%) had cervical kyphosis, all of whom
      except one had kyphosis >=20 degrees  at the thoracolumbar level. Two patients
      (16.7%) had atlantoaxial subluxation, and 10 patients (83.3%) had cervical
      vertebral malformations. Patients with mcEDS-CHST14 are susceptible to develop
      scoliosis, thoracolumbar kyphosis, and cervical kyphosis; and are recommended to
      have regular surveillance including total spine radiology. The present findings
      also suggest the critical role of dermatan sulfate in the development and
      maintenance of the spine.

PMID- 30195270
TI  - Novel rare variations in IRF6 in subjects with non-syndromic cleft lip and palate
      and dental agenesis.
AB  - OBJECTIVE: Subjects with cleft lip and palate (CLP) present high prevalence of
      dental agenesis. Among candidate genes for these phenotypes is IRF6. However,
      genetic studies do not analyze dental agenesis as a phenotype associated with
      cleft. Therefore, we investigated the frequency of rare and novel variations in
      IRF6 in subjects with non-syndromic unilateral cleft lip and palate (NSUCLP),
      with and without dental agenesis. SUBJECTS AND METHODS: Genomic DNA samples of
      100 subjects with NSUCLP with and without dental agenesis and 50 controls were
      sequenced. IRF6 mutational screening was conducted by direct sequencing. RESULTS:
      Ten new and rare missense variations were identified, two in the group cleft with
      agenesis and eight in the group cleft without agenesis, and none were found in
      control group. In silico analysis revealed four variations as potentially
      deleterious, being two in the group with cleft and agenesis and two in the group
      with cleft without agenesis. CONCLUSION: The study identified novel IFR6
      variations in subjects with NSUCLP with or without associated dental agenesis.
      The hypothesis of a higher frequency of deleterious variations in the subjects
      with cleft associated with dental agenesis, when compared to the group of cleft
      without agenesis and control without cleft, was not supported.

PMID- 30195271
TI  - Risk factors for mortality after respiratory syncytial virus lower respiratory
      tract infection in adults with hematologic malignancies.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) lower respiratory tract infection
      (LRTI) is associated with high mortality in patients with hematologic
      malignancies (HM). We sought to determine whether allogeneic hematopoietic cell
      transplant (allo-HCT) recipients would be at higher risk for 60-day mortality.
      METHODS: We examined a retrospective cohort of adults with HM with or without HCT
      treated for RSV LRTI (n = 154) at our institution from 1996-2013. We defined
      possible RSV LRTI as RSV detected only in the upper respiratory tract with new
      radiologic infiltrates and proven RSV LRTI as RSV detected in BAL fluid with new
      radiologic infiltrates. Immunodeficiency Scoring Index (ISI) and Severe
      Immunodeficiency (SID) criteria were calculated for HCT recipients. Multivariable
      logistic regression analyses were performed to identify independent risk factors
      associated with 60-day all-cause mortality. RESULTS: Mortality was high in HM
      patients (25%), but there was no difference between those without HCT, autologous
      or allo-HCT recipients in logistic regression models. Separate multivariate
      models showed that at RSV diagnosis, neutropenia (OR 8.3, 95% CI 2.8-24.2, P =
      0.005) and lymphopenia (OR 3.7, 95% CI 1.7-8.2, P = 0.001) were associated with
      60-day mortality. Proven LRTI was associated with higher 60-day mortality
      (neutropenia model: OR 4.7, 95%CI 1.7-13.5; lymphopenia model: OR 3.3, 95% CI 1.2
      8.8), and higher ICU admission. In HCT recipients, high ISI and very severe
      immunodeficiency by SID criteria were associated with higher 60-day all-cause
      mortality. CONCLUSIONS: Mortality is similarly high among HM patients without HCT
      and HCT recipients. High-grade immunodeficiency and detection of RSV from BAL
      fluid are associated with higher 60-day mortality.

PMID- 30195272
TI  - Heterometallic Cluster-Capped Tetrahedral Assemblies with Postsynthetic
      Modification of the Metal Cores.
AB  - Combining the star-shaped alkynyl ligands with low-nuclearity gold-copper
      triphosphane clusters produces 3D metallocage aggregates, which demonstrate room
      temperature phosphorescence in solution (max Phiem =0.6). Their luminescence
      mainly originates from cluster-localized metal-to-ligand charge transfer excited
      state. These supramolecular assemblies can be easily converted into the
      isostructural gold-silver congeners by the direct exchange of the metal ions.
      Such modification of the terminal metal cores switches the emission to the
      intraligand (alkyne) electronic transitions of the triplet manifold, that
      represents an unusual optical functionality among the metallocycle/metallocage
      complexes.

PMID- 30195273
TI  - Isoflavonoid-specific prenyltransferase gene family in soybean: GmPT01, a
      pterocarpan 2-dimethylallyltransferase involved in glyceollin biosynthesis.
AB  - Phytoalexin glyceollins are soybean-specific antimicrobial compounds that are
      derived from the isoflavonoid pathway. They are synthesized by soybean in
      response to extrinsic stress such as pathogen attack or injury, thereby
      conferring partial resistance if synthesized rapidly at the site of infection and
      at the required concentration. Soybean produces multiple forms of glyceollins
      that result from the differential prenylation reaction catalyzed by
      prenyltransferases (PTs) on either the C-2 or C-4 carbon of a pterocarpan
      glycinol. The soybean genome contains 77 PT-encoding genes (GmPTs) where at least
      11 are (iso)flavonoid-specific. Transcript accumulation of five candidates GmPTs
      was increased in response to Phytophthora sojae infection, suggesting their role
      in phytoalexin synthesis. The induced GmPTs localize to plastids and display
      tissue-specific expression. We have in this study identified two additional
      GmPTs: an isoflavone dimethylallyltransferase 3 (IDT3); and a glycinol 2
      dimethylallyl transferase GmPT01. GmPT01 prenylates (-)-glycinol at the C-2
      position, localizes in the plastid, and exhibits root-specific gene expression.
      Furthermore, its expression is induced rapidly in response to stress, and is
      associated with a quantitative trait loci linked with resistance to P. sojae.
      Based on these results, we conclude that GmPT01 are possibly one of the loci
      involved in conferring partial resistance against stem and root rot disease in
      soybean.

PMID- 30195274
TI  - Enhancing pediatric airway safety using the electronic medical record.
AB  - OBJECTIVE: Difficult intubations are not uncommon in tertiary care children's
      hospitals, and effective documentation of the difficult airway is a fundamental
      element of safe airway management. The primary goal of our quality improvement
      initiative was to improve access to airway information via an alert and
      documentation system within the electronic medical record (EMR). METHODS: We
      created a difficult airway alert within the EMR, linking common airway evaluation
      templates used by specialists involved in airway management. We assessed the time
      required for different specialists to answer an airway information questionnaire
      using the electronic charts of patients before and after the EMR modification.
      Satisfaction with the EMR modification was also surveyed. RESULTS: Questionnaires
      were administered to 12 participants before the Epic (Epic Systems Corp., Verona,
      WI) changes were implemented and to 19 participants after they were implemented.
      Each participant was asked to answer the airway data questionnaire for two
      patients, for a total of 24 questionnaires before the EMR changes and 38
      questionnaires after the changes. Respondents averaged 7.24 minutes to complete
      the entire airway data questionnaire before the EMR changes and 3.16 minutes
      following modification (P < 0.0001). Correct airway information was more
      consistently collected with the modified EMR (98.6% vs 51.4%, P < 0.00001).
      Satisfaction surveys revealed that participants found the accessibility of airway
      data to be significantly improved following the EMR changes. CONCLUSION: An EMR
      airway alert that provides rapid access to relevant airway information critical
      tool during urgent and emergent events. Based on our preliminary data, further
      use of this instrument is expected to continue to improve patient safety and
      practitioner satisfaction. LEVEL OF EVIDENCE: 4. Laryngoscope, 2018.

PMID- 30195275
TI  - Adenoidectomy With Balloon Catheter Sinuplasty: A Randomized Trial for Pediatric
      Rhinosinusitis.
AB  - OBJECTIVES/HYPOTHESIS: To compare treatment outcomes in pediatric patients with
      chronic rhinosinusitis (CRS) using adenoidectomy and maxillary sinus irrigation
      with or without balloon catheter sinuplasty (BCS). METHODS: Prospective,
      randomized, and blinded. Patients between 2 and 12 years who met clinical and
      computed tomography criteria for CRS unresponsive to maximal medical therapy and
      no prior sinus- or adenoid-related procedures were eligible. Twenty-five patients
      were randomized, had surgery, and completed the follow-up. The control group
      underwent adenoidectomy with maxillary sinus irrigation alone; the treatment
      group underwent the same, with the addition of maxillary BCS for the maxillary
      sinus irrigation. Patients and parents were blinded to group assignment
      throughout the follow-up time frame. A validated questionnaire, the Sinus and
      Nasal Quality of Life Survey (SN-5), was used to measure health status changes
      and quality of life (QOL) at baseline, 6 months, and 12 months postintervention.
      Data was analyzed using t tests and multivariate linear regression. RESULTS:
      There were 12 patients in the BCS group and 13 in the control group. Other than a
      higher atopic history in the control group (P = 0.047), there were no significant
      differences (P = 0.07) in the two groups (demographics and baseline SN-5 scores).
      Following surgery, both groups demonstrated similar improvement in QOL scores and
      median SN-5 scores in all domains (number of sinus infections, nasal obstruction,
      allergy symptoms, emotional distress, and activity limitations). CONCLUSION: The
      addition of BCS to adenoidectomy/maxillary sinus irrigation did not provide
      additional QOL and sinonasal symptom improvement in the surgical treatment of
      pediatric CRS. LEVEL OF EVIDENCE: 1b. Laryngoscope, 2017.

PMID- 30195276
TI  - [Clinical experience on a case of osteomyelitis treated with dalbavancin].

PMID- 30195277
TI  - [Research on Identification of Organic Gunshot Residue with Micro-Raman
      Spectroscopy].
AB  - A rapid approach for the nondestructive, accurate detection of organic gunshot
      residue was investigated. Raman microscopy was used to identify organic gunshot
      residue and the propellant in ammunition. The optimal excitation wavelength for
      the detection of organic particles using Raman spectroscopy was 473 nm. The Raman
      spectra of organic gunshot residue obtained using 473 nm laser excitation can
      effectively avoid the interference of fluorescence. The results demonstrated that
      the organic particles were mainly from the partially burned propellant particles.
      Meanwhile it was proved that the main component was basically consistent with the
      propellant except somehow damage in chemical structure or degree of
      crystallization with Raman spectra. The surface color of organic particles was
      mainly brassiness, dark gray. A lot of craters were distributed on the surface of
      organic particles. Spherical inorganic particles with metallic luster attached to
      the surface of organic particles can be regarded as the typical characteristics
      of gunshot residue.

PMID- 30195278
TI  - [The Study of Methodology Validation in Multicomponent Quantitative Analysis of
      Raman Spectroscopy].
AB  - Raman spectroscopy with the help of sophisticated data analysis techniques based
      on multivariate analysis have made it possible to study the full information of
      Raman spectra and to draw conclusions about the chemical structure and
      composition of very complex systems. As Raman spectroscopy has the advantage to
      provide rich information of the sample, so it was first included in Chinese
      Pharmacopoeia (2010) as "Annex XIX L Guidelines of Raman spectroscopy". However
      the validation method for multicomponent quantitative analysis of Raman
      spectroscopy was not discussed in this pharmacopoeia. The purpose of this study
      was to develop innovatively the validation method for the Raman model in
      multicomponent quantitative analysis. Two kinds of samples with different matrix
      background were used to study the self-performance test of the instrument,
      linearity, limit of quantitation, accuracy and precision, respectively. As the
      sample was complex composition in our study, so there is no need to provide
      sample blank and rupture test for specificity study which was carried out in the
      traditional method of experiments. As the result showed, we propose a validation
      method for Raman spectroscopy in multicomponent analysis for the further study
      and improvement of standards of the method.

PMID- 30195279
TI  - [Application of Raman Spectroscopy and Pattern Recognition Methods for
      Determining the Authenticity and Detecting the Adulteration of Milk Powder].
AB  - The authenticity and adulteration of dairy products are attracting broad
      attention in recent years. There is a need to develop rapid, simple and accurate
      analytical methods for the detection of authenticity and adulteration of dairy
      products. To discriminate between milk powder samples, Raman spectra of FIRMUS,
      Nestle and Being Mate milk powder were collected. The nearest neighbor algorithm
      (NN)combined with the characteristic peaks were employed for the design of a
      model. On the basis of 10 cross validation, the average recognition rate was
      99.56%. In order to achieve the analysis of the adulteration of milk powder,
      FIRMUS milk powder was mixed with Nestle milk powder according to the mass ratio
      0 :1, 1 : 3, 1 : 1, 3 : 1 and 1 : 0 to get five kinds of the adulterated milk
      powder samples. Then, fat was extracted from the adulterated milk powder samples.
      Raman spectra of the fat were collected, then two methods were employed for the
      design of models. One was the nearest neighbor algorithm combined with the
      characteristic peaks, another was the kernel principal component analysis (KPCA)
      combined with NN. On the basis of 10 cross validation, the average recognition
      rate reached 93.33% and 98.89%, the average operation time was 0.085 and 0.104 s.
      The results of this work showed that the nearest neighbor algorithm combined with
      the characteristic peaks can be applied for the determination of the authenticity
      of milk powder while Raman-KPCA-NN model can provide a simple, accurate and rapid
      method to investigate the adulteration of milk power.

PMID- 30195280
TI  - [Fast Classification of Complex Sulphide Ore Based on Raman Spectroscopy].
AB  - The regional features, metallogenitic regularities and mineral composition of the
      hydrothermal sulphide ore have been preliminarily studied. According to the
      different mineralization period, the patterns of valuable minerals disseminated
      in ore are complicated, which causes the large changes in the properties of the
      sulphide ore. The different properties of the sulphide ore may increase the
      difficulty of the mineral processing and reduce the recovery rate of valuable
      minerals. Therefore a simple method for rapidly classification of sulphide ore is
      required to optimize mineral processing flowsheet. Laser Raman spectrometry, as
      an effective method to analyze the structure of the material is used to identify
      the component and structure of minerals. The research on the Laser Raman spectra
      of the large number of sulphide ore samples can reveal the reasons for the
      difference of the Raman spectra. A new method for classifying the complex
      sulphide ore using Raman spectroscopy is proposed. The experiment results
      demonstrate that the properties of the sulphide ore in different mineralization
      period vary greatly and the fluorescent scattering is mainly produced by gangue
      minerals. The measured Raman spectral after quenching the fluorescence scattering
      show the peaks of Raman spectra at 201.62, 242.54, 288.38 and 309.77 cm-1 can be
      used to identify this kind of complex sulphide ore. The raw ore can be divided
      into three categories based on the difference of the intensity of fluorescence
      scattering and the ratio of fluorescence and Raman intensity. The accuracy of the
      classification method is further validated by the industrial tests. The findings
      demonstrate the close relationship between Raman spectra and the properties of
      sulphide ore. The proposed method, which can fast classify the sulphide ore,
      don't need complex chemical pretreatment before spectra collection. Therefore,
      this method will have important application value for improving the efficiency of
      mineral processing.

PMID- 30195281
TI  - [Density Functional Theory Calculation and Raman Spectroscopy Studies of
      Organophosphorus Pesticides].
AB  - Organophosphorus pesticides were often used for prevention and control disease
      and insect of plant, and are acute toxic to human and livestock by anti-ache
      activity. The molecular geometry of three organophosphorus pesticides(dimethoate,
      trichlorfon and phosalone) were constructed on Gauss View3.07, and Density
      functional theory (DFT) was used to optimize and calculate the vibrational
      wavenumbers of three organophosphorus pesticides by B3LYP hybrid functional and 6
      31G(d, p) basis set. The experimental spectra of three organophosphorus
      pesticides were compared with the theoretically calculated spectra and Surface
      enhanced Raman Scattering spectra (SERS). The results indicated that the
      experimental spectra and theoretically calculated spectra of three
      organophosphorus pesticides have a very good match. The Raman peaks of three
      organophosphorus pesticides were roundly assigned between the range of 400~1 800
      cm(-1), and the characteristics peaks of three organophosphorus pesticides were
      found. The Raman vibration peak of organophosphorus pesticide may appear similar
      characteristic peak. The pesticide contained PO is between 1 140 and 1 320 cm(
      1), the pesticide contained PS is in the range 535~750 cm(-1), and the
      organophosphorus pesticide contained P-O-C is n the range 920~1 088 cm-1. The
      different characteristic peaks of three pesticides were found by the contrast of
      the surface enhanced Raman spectra. This shows that the SERS method can be used
      to identify the organophosphorus pesticide. The results can furnish a theoretical
      support for qualitative and quantitative analysis of organophosphorus pesticide.

PMID- 30195282
TI  - [The Study of Three-Dimensional Synchronous Fluorescence Spectral Characteristics
      of Liuwei Dihuang Pills].
AB  - Three-dimensional synchronous fluorescence of each component of Liuwei dihuang
      pills (Prepared rehmannia root, cornel, yam, alisma, poria cocos, and cortex
      moutan) is measured by using FLS920P fluorescence spectrometer. Feature
      parameters were extracted. It can be found that each component is fluorescent
      material and the lines are all different. Furthermore, Three-dimensional
      synchronous fluorescence of Liuwei dihuang pills boiling with standard water and
      non-standard water are all measured and there are significant differences between
      them. It can be applied in distinguishing different formula of Chinese medicine
      decoction. Experimental and Theoretical conclusion show that: the three
      dimensional fluorescence spectrometry method and the combination of synchronous
      fluorescence spectroscopy method can further improve the sensitivity and
      selectivity of fluorescence spectroscopy, have a distinct advantage in a complex
      multi-component mixture of fluorescence spectroscopic analysis. The study can
      provide a convenient and reliable method for establishing a complete fingerprint
      of Chinese traditional medicine. It also can help identifying the component and
      the quality of Chinese patent medicine.

PMID- 30195283
TI  - [Rapid Method for Determination of Furfural and 5-Hydroxymethyl Furfural of
      Ethanol-Water Hydrolysate of Biomass with UV Spectroscopy].
AB  - The soluble lignin and furan compounds in hydrolysate of lignocellulose biomass
      have absorbed peaks and inter-superimpose in UV spectroscopy. Therefore, this
      paper developed a method for the determination of furfural and 5-hydroxymethyl
      furfural in ethanol-water refining liquors of lignocellulose biomass based on UV
      spectroscopy. The study showed that there is a good and linear relationship
      between maximum absorption (lambdamax) and the concentration percent of 5-HMF
      (W(5-HMF)) of M, the regression coefficient up to 0.998 4 (R(2)=0.998 4).
      Furthermore, a better linear relationship was also observed between the
      concentration of mixture (cM) and absorptivity (A) when the W(5-HMF) was
      constant, the R(2) of 0.998 6~1.000 0 and reproducibility are desirable. The
      contents of F and 5-HMF could be calculated accurately according to the perfect
      liner relationship of A and c(M), lambda(max) and W(5-HMF), and the relative
      deviation of F and 5-HMF of 5.6% and 3.7%, recovery of 89%~96%, RSD of
      0.21%~0.85%, respectively. Overall, The simple rapid and precise method in this
      paper can be applied to the determination of the F and 5-HMF in the hydrolysate
      of ethanol-water refining lignocellulose biomass.

PMID- 30195284
TI  - [Visual Detection Study on Early Bruises of Korla Pear Based on Hyperspectral
      Imaging Technology].
AB  - In this paper, hyperspectral imaging combined with chemometrics was applied for
      the detection of internal defects of Korla pear. The hyperspectral images
      covering the spectral range of 380~1 030 nm were acquired for 60 Korla pears
      before, and seven consecutive days after internal damages were induced by being
      dropped from a distance of 30 cm. The mean spectrum were computed from region of
      interests (ROI) of pear in each image, and was preprocessed with wavelet
      transform for eliminating system noise and external disturbances, and optimizing
      the spectral identification region (470~963 nm). Based on the preprocessed
      samples, the support vector machine models were built respectively through the
      full and feature wavebands selected by the second derivative. The results on
      testing set demonstrate that both of the two approaches achieved the
      discrimination accuracy of 93.75%. Furthermore, F-value based method was applied
      for image analysis to find out the optimal waveband ratio for the visual
      discrimination of bruises against normal surface. Based on the optimal waveband
      ratio images, the selective search algorithm was utilized for segmenting bruises
      from the pear surface, and shows the accurate identification results. Our
      research revealed that the hyperspectral imaging technique for detecting bruised
      features in pears is feasible, which could provide a theoretical reference and
      basis for designing classification system of fruits in further work.

PMID- 30195285
TI  - [Estimation Models for Jujube Leaf Pigment Concentration with Hyperspectrum Data
      at Canopy Scale].
AB  - Plant canopy pigment concentration is a critical variable for agricultural remote
      sensing due to its close relationship to leaf nitrogen content. The aims of this
      study were to: (1) compare the prediction performances on chlorophyll,
      chlorophyll-a and b, and carotenoid concentration in jujube leaf at canopy scale
      between partial least squares regression (PLSR) and support vector machine (SVM),
      (2) develop quantitative models to estimate pigment concentration in jujube
      canopy using hyperspectral data and provide theoretical and technical support for
      rapidly, non-destructive, less expensive and eco-friendly measuring the
      concentration. Results from correlation analysis showed that jujube canopy
      pigment concentration correlated strongly with hyperspectral data. What's more,
      the hyperspectral data was better correlated by chlorophyll and chlorophyll-a
      than chlorophyll-b and carotenoid. Results of independent samples tested in
      predicting performance indicated that both of the PLSR and SVM models could
      effectively estimate pigment concentration, however, with different prediction
      precisions. Additionally, the precision of SVM outperformed PLSR for predicting
      chlorophyll and carotenoid. Whereas chlorophyll-a and chlorophyll-b were better
      predicted using PLSR than SVM. Compared among all the pigments' prediction
      precisions with corresponding optimal inversion models showed that prediction
      precisions on chlorophyll, chlorophyll-a and carotenoid were superior to
      chlorophyll-b. The determination coefficients and residual prediction deviation
      from predicting chlorophyll, chlorophyll-a and carotenoid were higher than 0.8
      and 2.0, respectively, while the mean relative error values were lower than 13%.
      And the corresponding values from predicting chlorophyll-b were 0.60%, 20.79% and
      1.79% respectively.

PMID- 30195286
TI  - [Tongue Coat Information Extraction of the Traditional Chinese Medicine with
      Hyperspectral Image].
AB  - Tongue coat information extraction plays an important role in disease diagnosis
      for the traditional Chinese medicine. For the purpose of quantifying the tongue
      coat properties in traditional Chinese medicine, most of the existing methods are
      based on computerized image analysis, carrying out RGB color space in a tongue
      imaging captured with digital camera. However, those methods cannot meet the
      requirements of clinical medicine. To explore more information about the tongue
      objectively, a new approach to analyze tongue information based on hyperspectral
      images is presented. Hyperspectral images are acquired using the hyperspectral
      imaging system in the spectral range of 370.200 0 to 992.956 0 nm (343bands), and
      the traditional Chinese medicine clinical diagnosis information is recorded. The
      main region of interest (ROI) in the samples is extracted while the background is
      removed from the tongue image, then tongue information of ROI is analyzed. The
      largest different spectral characteristics between tongue proper and tongue coat
      are found in the wavelength range of about 525 to 600 nm. Nine wavelengths tongue
      spectral images from 382.108 0 to 963.668 0 nm are extracted, then comparing with
      the actual tongue situation, we find that the spectral image at 527.548 0 nm band
      can better reflect the actual tongue situation than others. The experiment
      results show that hyperspectral imaging technique is very helpful for tongue coat
      information extraction of the traditional Chinese medicine, and this new analysis
      approach can provide a fast and simple non-invasive detection method for tongue
      coat segmentation and tongue coat information extraction.

PMID- 30195287
TI  - The C(3P) + NO(X2Pi) -> O(3P) + CN(X2Sigma+), N(2D)/N(4S) + CO(X1Sigma+)
      reaction: Rates, branching ratios, and final states from 15 K to 20 000 K.
AB  - The C + NO collision system is of interest in the area of high-temperature
      combustion and atmospheric chemistry. In this work, full dimensional potential
      energy surfaces for the 2A', 2A", and 4A" electronic states of the [CNO] system
      have been constructed following a reproducing kernel Hilbert space approach. For
      this purpose, more than 50 000 ab initio energies are calculated at the
      MRCI+Q/aug-cc-pVTZ level of theory. The dynamical simulations for the C(3P) +
      NO(X2Pi) -> O(3P) + CN(X2Sigma+), N(2D)/N(4S) + CO(X1Sigma+) reactive collisions
      are carried out on the newly generated surfaces using the quasiclassical
      trajectory (QCT) calculation method to obtain reaction probabilities, rate
      coefficients, and the distribution of product states. Preliminary quantum
      calculations are also carried out on the surfaces to obtain the reaction
      probabilities and compared with QCT results. The effect of nonadiabatic
      transitions on the dynamics for this title reaction is explored within the Landau
      Zener framework. QCT simulations have been performed to simulate molecular beam
      experiment for the title reaction at 0.06 and 0.23 eV of relative collision
      energies. Results obtained from theoretical calculations are in good agreement
      with the available experimental as well as theoretical data reported in the
      literature. Finally, the reaction is studied at temperatures that are not
      practically achievable in the laboratory environment to provide insight into the
      reaction dynamics at temperatures relevant to hypersonic flight.

PMID- 30195288
TI  - Laser cooling of thallium chloride: A theoretical investigation.
AB  - The possibility of laser cooling of thallium chloride (TlCl) molecules has been
      investigated based on high-level ab initio calculations with the consideration of
      the core-valence and the spin-orbit coupling (SOC) effects. The potential energy
      curves of the 13 Lambda-S states as well as the 24 Omega states split from them
      via SOC are obtained by multi-reference configuration interaction plus the
      Davidson correction. We show that the a Pi0+3-X1Sigma0+ transition of TlCl is a
      possible candidate for laser cooling, which features highly diagonal Franck
      Condon factors and no intermediate interacting electronic states. Based on our
      calculations, we propose an optical cycling scheme by utilizing four lasers at
      wavelengths around 320 nm with more than 104 cycles for photon
      absorption/emission and a sub-microkelvin temperature limit.

PMID- 30195289
TI  - Automated design of collective variables using supervised machine learning.
AB  - Selection of appropriate collective variables (CVs) for enhancing sampling of
      molecular simulations remains an unsolved problem in computational modeling. In
      particular, picking initial CVs is particularly challenging in higher dimensions.
      Which atomic coordinates or transforms there of from a list of thousands should
      one pick for enhanced sampling runs? How does a modeler even begin to pick
      starting coordinates for investigation? This remains true even in the case of
      simple two state systems and only increases in difficulty for multi-state
      systems. In this work, we solve the "initial" CV problem using a data-driven
      approach inspired by the field of supervised machine learning (SML). In
      particular, we show how the decision functions in SML algorithms can be used as
      initial CVs (SMLcv ) for accelerated sampling. Using solvated alanine dipeptide
      and Chignolin mini-protein as our test cases, we illustrate how the distance to
      the support vector machines' decision hyperplane, the output probability
      estimates from logistic regression, the outputs from shallow or deep neural
      network classifiers, and other classifiers may be used to reversibly sample slow
      structural transitions. We discuss the utility of other SML algorithms that might
      be useful for identifying CVs for accelerating molecular simulations.

PMID- 30195290
TI  - The origin of the conductivity maximum vs. mixing ratio in pyridine/acetic acid
      and water/acetic acid.
AB  - Explanations are provided for the first time for the historically known locations
      of electrical conductivity maxima versus mixing ratio (mole fraction of acid, xA)
      in mixtures of (i) acetic acid with water and (ii) acetic acid with pyridine. To
      resolve the question for the second system, density-functional-based molecular
      dynamic simulations were performed, at 1:1, 1:2, 1:3, 1:5, and 1:15 mixing
      ratios, to gain vital information about speciation. In a zeroth-order picture,
      the degree of ionization (and hence conductivity) would be maximal at xA = 0.5,
      but these two examples see this maximum shifted to the left (water/acetic acid,
      xAmax = 0.06), due to improved ion stability when the effective dielectric
      constant is high (i.e., water-rich mixtures), or right (pyridine/acetic acid
      xAmax = 0.83), due to improved acetate stability via "self-solvation" with acetic
      acid molecules (i.e., acid-rich mixtures) when the dielectric constant is low. A
      two-parameter equation, with theoretical justification, is shown to reproduce the
      entire 0 < xA < 1 range of data for electrical conductivity for both systems.
      Future work will pursue the applicability of these equations to other
      amine/carboxylic acid mixtures; preliminary fits to a third system
      (trimethylamine/acetic acid) give curious parameter values.

PMID- 30195291
TI  - The Ehrenfest method with fully quantum nuclear motion (Qu-Eh): Application to
      charge migration in radical cations.
AB  - An algorithm is described for quantum dynamics where an Ehrenfest potential is
      combined with fully quantum nuclear motion (Quantum-Ehrenfest, Qu-Eh). The method
      is related to the single-set variational multi-configuration Gaussian approach
      (vMCG) but has the advantage that only a single quantum chemistry computation is
      required at each time step since there is only a single time-dependent potential
      surface. Also shown is the close relationship to the "exact factorization
      method." The quantum Ehrenfest method is compared with vMCG for study of electron
      dynamics in a modified bismethylene-adamantane cation system. Illustrative
      examples of electron-nuclear dynamics are presented for a distorted allene system
      and for HCCI+ where one has a degenerate Pi system.

PMID- 30195292
TI  - Influence of mass and potential energy surface geometry on roaming in
      Chesnavich's CH4+ model.
AB  - Chesnavich's model Hamiltonian for the reaction CH4+-> CH3+ + H is known to
      exhibit a range of interesting dynamical phenomena including roaming. The model
      system consists of two parts: a rigid, symmetric top representing the CH3+ ion
      and a free H atom. We study roaming in this model with focus on the evolution of
      geometrical features of the invariant manifolds in phase space that govern
      roaming under variations of the mass of the free atom m and a parameter a that
      couples radial and angular motion. In addition, we establish an upper bound on
      the prominence of roaming in Chesnavich's model. The bound highlights the
      intricacy of roaming as a type of dynamics on the verge between isomerisation and
      nonreactivity as it relies on generous access to the potential wells to allow
      reactions as well as a prominent area of high potential that aids sufficient
      transfer of energy between the degrees of freedom to prevent isomerisation.

PMID- 30195293
TI  - Evaporation-induced assembly of colloidal crystals.
AB  - Colloidal crystals are often prepared by evaporation from solution, and there is
      considerable interest to link the processing conditions to the crystal morphology
      and quality. Here, we study the evaporation-induced assembly of colloidal
      crystals using massive-scale nonequilibrium molecular dynamics simulations. We
      apply a recently developed machine-learning technique to characterize the
      assembling crystal structures with unprecedented microscopic detail. In agreement
      with previous experiments and simulations, faster evaporation rates lead to
      earlier onset of crystallization and more disordered surface structures.
      Surprisingly, we find that collective rearrangements of the bulk crystal during
      later stages of drying reduce the influence of the initial surface structure, and
      the final morphology is essentially independent of the evaporation rate. Our
      structural analysis reveals that the crystallization process is well-described by
      two time scales, the film drying time and the crystal growth time, with the
      latter having an unexpected dependence on the evaporation rate due to equilibrium
      thermodynamic effects at high colloid concentrations. These two time scales may
      be leveraged to control the relative influence of equilibrium and nonequilibrium
      growth mechanisms, suggesting a route to rapidly process colloidal crystals while
      also removing defects. Our analysis additionally reveals that solvent-mediated
      interactions play a critical role in the crystallization kinetics and that
      commonly used implicit-solvent models do not faithfully resolve nonequilibrium
      processes such as drying.

PMID- 30195294
TI  - Adsorption of common solvent molecules on graphene and MoS2 from first
      principles.
AB  - Solvents are an essential element in the production and processing of two
      dimensional (2D) materials. For example, the liquid-phase exfoliation of layered
      materials requires a solvent to prevent the resulting monolayers from re
      aggregating, while solutions of functional atoms and molecules are routinely used
      to modify the properties of the layers. It is generally assumed that these
      solvents do not interact strongly with the layer and so their effects can be
      neglected. Yet experimental evidence has suggested that explicit atomic-scale
      interactions between the solvent and layered material may play a crucial role in
      exfoliation and cause unintended electronic changes in the layer. Little is known
      about the precise nature of the interaction between the solvent molecules and the
      2D layer. Here, we use density functional theory calculations to determine the
      adsorption configuration and binding energy of a variety of common solvent
      molecules, both polar and non-polar, on two of the most popular 2D materials,
      namely, graphene and MoS2. We show that these molecules are physisorbed on the
      surface with negligible charge transferred between them. We find that the
      adsorption strength of the different molecules is independent of the polar nature
      of the solvent. However, we show that the molecules induce a significant charge
      rearrangement at the interface after adsorption as a result of polar bonds in the
      molecule.

PMID- 30195295
TI  - Communication: Long range corrections in liquid-vapor interface simulations.
AB  - Long range corrections (lrc) for the potential energy and for the force in planar
      liquid-vapor interface simulations are considered for spherically symmetric
      interactions. First, it is stated that for the Lennard-Jones (LJ) fluid the lrc
      for the energy Deltau of Janecek [J. Phys. Chem. B 110, 6264 (2006)] is the same
      as that of Lotfi et al. [Mol. Simul. 5, 233 (1990)]. Second, we present the lrc
      for the force Delta F for any spherically symmetric interaction as a derivative
      of Deltau plus a surface integral over the cut-off sphere by using the extended
      Leibniz rule of Flanders [Am. Math. Monthly 80, 615 (1973)]. This Delta F
      corrects the incomplete lrc Delta1F of Lotfi et al. and agrees with the result of
      Janecek obtained by direct averaging of the forces. Third, we show that the
      molecular dynamics (MD) results for the surface tension gamma of the LJ fluid
      with size parameter sigma obtained by Werth et al. [Physica A 392, 2359 (2013)]
      with the lrc Delta F of Janecek and a cut-off radius rc = 3sigma agree with the
      results of Mecke et al. [J. Chem. Phys. 107, 9264 (1997)] obtained with the lrc
      Delta1F of Lotfi et al. and rc = 6.5sigma within -0.4% to +1.6%. Moreover, using
      only the MD results for gamma of Werth et al., we obtain for the LJ fluid a new
      surface tension correlation which also represents the gamma-values of Mecke et
      al. within +/-0.7%. The critical temperature resulting from the correlation is Tc
      = 1.317 66 and is in very good agreement with Tc,ref = 1.32 of the reference
      equation of state for the LJ fluid given by Thol et al. [J. Phys. Chem. Ref. Data
      45, 023101 (2016)].

PMID- 30195296
TI  - Bimolecular multistage diffusion-influenced chemical reactions proceeding from
      different sites in solutions. I. Rate constants.
AB  - General matrix algebraic equations for calculating rate constants of multistage
      diffusion-influenced reactions (involving bimolecular exchange reactions as
      elementary stages) in liquid solutions that proceed from different active sites
      in the immediate vicinity of the contact of reactants have been obtained on the
      basis of the kinematic approximation developed by the authors earlier. The
      equations make it possible to express rate constants of any multistage multisite
      bimolecular reaction between non-identical reactants in terms of the defined
      reaction constants and stationary Green functions averaged over reaction sites
      and completely determined by molecular motion of reactants or their molecular
      groups. The asymptotic behavior of these rate constants as they attain their
      steady-state values on completion of the transient stage is established. It is
      shown that it coincides with the corresponding exact time asymptote. Calculations
      are made with some specific two-stage (three-channel) bimolecular reactions as an
      example.

PMID- 30195297
TI  - Long time scale dynamics of vibrationally excited (HBr)n clusters.
AB  - We investigated the photodissociation dynamics of vibrationally excited HBr
      molecules and clusters. The species were generated in a molecular beam and
      excited with an IR laser to a v = 1 vibrational state. A subsequent ultraviolet
      (UV)-pulse with 243 nm radiation photolysed the molecules to yield H-fragments,
      which were resonantly ionized by the same UV-pulse (2 + 1 REMPI) and detected in
      a velocity map imaging (VMI) experiment. We performed action spectroscopy to
      distinguish between two expansion regimes: (i) expansion leading to isolated HBr
      molecules and (ii) generation of large (HBr)n clusters. Photodissociation of
      isolated HBr ( v = 1) molecules in particular J ro-vibrational states yielded
      faster H-fragments (by approximately 0.3 eV) with respect to the
      photodissociation of the ground state HBr ( v = 0). On the contrary, the IR
      excitation of molecules in (HBr) n clusters enhanced the yield of the H-fragments
      UV-photodissociated from the ground-state HBr ( v = 0) molecules. Our findings
      show that these molecules are photodissociated within clusters, and they are not
      free molecules evaporated from clusters after the IR excitation. Nanosecond IR-UV
      pump-probe experiments show that the IR-excitation enhances the H-fragment UV
      photodissociation yield up to ~100 ns after the IR excitation. After these long
      IR-UV delays, excitation of HBr molecules in clusters does not originate from the
      IR-excitation but from the UV-photodissociation and subsequent caging of HBr
      molecules in v > 0 states. We show that even after ~100 ns the IR-excited larger
      (HBr) n clusters do not decay to individual molecules, and the excitation is
      still present in some form within these clusters enhancing their UV
      photodissociation.

PMID- 30195298
TI  - Looking at the dynamical heterogeneity in a supercooled polymer system through
      isoconfigurational ensemble.
AB  - The dynamic correlations that emerge in a polymer system in supercooling
      conditions have been studied using molecular dynamic simulations. It is known
      that when a glass former approaches the glass transition temperature, the
      dynamics of the system (in terms of the mobilities of the particles) not only
      significantly slows down but also becomes more heterogeneous. Several theories
      relate this slowing down to increasing spatial (structural) correlations, for
      example, through the onset of cooperative relaxation regions in the Adam-Gibbs
      theory. In this work, we employ Pearson's coefficient in the isoconfigurational
      ensemble (ICE) which allows us to study the dynamic correlations of the monomers
      in the ICE and establish the relation between the structure of the monomers and
      its dynamic behavior. Similar to what happens with mobility, monomers with
      highest correlation are clustered, and the clustering increases with decreasing
      temperature. An interesting result is that regions with high ICE dynamic
      correlation are not coincident with highly mobile or immobile regions. These
      results represent a new approach to the study of dynamic heterogeneity that
      emerges in glass forming liquids, complementing the more traditional
      characterization in terms of mobility. The methodology proposed in this work that
      characterize the connected dynamic regions to structural causes can represent an
      alternative way to observe the cooperative relaxation regions.

PMID- 30195299
TI  - Reinterpretation of the electronic absorption spectrum of the methylene amidogen
      radical (H2CN).
AB  - The peculiar electronic absorption spectrum of H2CN has been of great interest to
      experiment. Herein, this system is studied extensively by applying theoretical
      methods to the ground and low-lying excited electronic states. Employing a large
      breadth of high-level ab initio computations, including coupled cluster [CCSD(T)
      and CCSDT(Q)] and multireference configuration interaction [MRCISD+Q] methods, we
      comprehensively demonstrate that the most recent experimental and theoretical
      interpretations of the electronic spectrum of H2CN are in error. The previous
      assignments of the two broad features in the spectrum as the origin 000 (~35 050
      cm-1) and 402 (~35 600 cm-1) B 2A1<-X 2B2 transitions are both found to be
      incorrect. The presently reported transition energies suggest that the higher
      energy band near 35 600 cm-1 is the true origin band. Additionally, from the
      computed anharmonic vibrational frequencies of the X 2B2 and B 2A1 states, we
      show that this ~550 cm-1 band spacing cannot be attributed to a simple vibronic
      transition, as claimed by the 402 assignment. Possible alternative explanations
      for the appearance of the lower intensity band near 35 050 cm-1 are discussed.

PMID- 30195300
TI  - Orbital-free density functional theory simulation of collective dynamics coupling
      in liquid Sn.
AB  - The appearance of a second excitation mode in the longitudinal and transverse
      collective dynamics of a series of liquid metals has been observed recently,
      either by inelastic X-ray scattering (IXS) or by first-principles molecular
      dynamics (FPMD). The phenomenon's origin is still uncertain, although some
      theories have been used with relative success to reproduce the FPMD results as a
      means to find an explanation for it (e.g., mode-coupling (MC) theory in liquid
      zinc [B. G. del Rio and L. E. Gonzalez, Phys. Rev. B 95, 224201 (2017)]). For
      liquid tin (l-Sn), the second excitation mode in the dynamic structure factor and
      longitudinal current spectrum was observed by IXS [S. Hosokawa et al., J. Phys.:
      Condens. Matter 25, 112101 (2013)]. By performing orbital-free density functional
      theory MD simulations of l-Sn, we confirm the existence of a second excitation
      mode in the longitudinal and transverse collective dynamics and provide a
      theoretical explanation based on MC theory. Moreover, we introduce a new binary
      term in MC theory to better capture the negative minima present in the memory
      functions of the collective dynamics. These results confirm that the origin of
      the second excitation mode exhibited by the longitudinal and transverse
      collective dynamics in some liquid metals involves an indirect coupling of the
      longitudinal and transverse modes.

PMID- 30195301
TI  - New insights into the atomic structure of amorphous TiO2 using tight-binding
      molecular dynamics.
AB  - Amorphous TiO2 (a-TiO2) could offer an attractive alternative to conventional
      crystalline TiO2 phases for photocatalytic applications. However, the atomic
      structure of a-TiO2 remains poorly understood with respect to that of its
      crystalline counterparts. Here, we conduct some classical molecular dynamics
      simulations of a-TiO2 based on a selection of empirical potentials. We show that,
      on account of its ability to dynamically assign the charge of each atom based on
      its local environment, the second-moment tight-binding charge equilibration
      potential yields an unprecedented agreement with available experimental data.
      Based on these simulations, we investigate the degree of order and disorder in a
      TiO2. Overall, the results suggest that a-TiO2 features a large flexibility in
      its local topology, which may explain the high sensitivity of its structure to
      the synthesis method being used.

PMID- 30195302
TI  - Influence of spatial degeneracy on rotational spectroscopy: Three-wave mixing and
      enantiomeric state separation of chiral molecules.
AB  - Pulse flip angles are calculated for three-wave mixing, three-state cycles of
      chiral molecules to produce optimized free induction decay amplitudes
      proportional to the enantiomeric excess of a sample and to produce optimized
      degrees of state-specific enantiomeric separation. The calculations account for
      the spatial degeneracy of the levels involved and the resulting inhomogeneous
      distribution of transition dipole moments. Cycles of transitions that include R
      followed by Q followed by P branch transitions display only modest reductions of
      the calculated optimal signals compared to those calculated if every M component
      was optimally polarized. Transition cycles P-Q-R are only slightly worse, while
      the Q-Q-Q cycles are much worse, increasingly so, as the rotational total quantum
      number is increased.

PMID- 30195303
TI  - Predicted infrared spectra in the HF stretching band of the H2-HF complex.
AB  - The infrared spectra with hydrogen fluoride (HF) and deuterium fluoride (DF) (v2
      = 1 <- 0) for eight isotropic species of H2-HF complex are predicted, based on
      our newly constructed high-accuracy ab initio potential energy surface [D. Yang
      et al., J. Chem. Phys. 148, 184301 (2018)]. The radial discrete variable
      representation/angular finite basis representation method and Lanczos algorithm
      were used to determine the ro-vibrational energy levels and wave functions for
      eight species of H2-HF complex (para-H2-HF, ortho-H2-HF, para-D2-HF, ortho-D2-HF,
      para-H2-DF, ortho-H2-DF, para-D2-DF, and ortho-D2-DF) with separating the inter-
      and intra-molecular vibrations. Bound states properties including their
      dissociation energies and rotational constants were presented. The calculated
      band origins are all red shifted to the isolated HF molecule and in good
      agreement with available experimental values. The frequencies and line
      intensities of ro-vibrational transitions in the HF stretching band were further
      calculated, and the predicted infrared spectra are consistent with available
      observed spectra. Among them, the spectra for three isotopic species of H2-HF
      (para-H2-DF, para-D2-DF, and ortho-D2-DF) were predicted for the first time.

PMID- 30195304
TI  - Efficient lattice constants and energy bandgaps for condensed systems from a meta
      GGA level screened range-separated hybrid functional.
AB  - A meta-generalized gradient approximation (meta-GGA) level screened hybrid
      functional is developed for the solid-state electronic structure calculations.
      Assessment of the proposed functional for the solid-state lattice constants and
      bandgaps indicates that it is quite efficient in describing those properties.
      Specifically, the improvement in the bandgap performance of the presently
      proposed meta-GGA level screened hybrid functional is noticeable. From the
      construction point of view, the present screened hybrid functional is one step
      forward to the density functional screened hybrid functional rung by adding extra
      ingredients in its functional form. The most appealing feature of the present
      screened functional is that it is constructed upon an accurate semilocal
      functional by adopting a simple modification on the top of that functional.

PMID- 30195305
TI  - Exchange-repulsion energy in QM/EFP.
AB  - The effective fragment potential (EFP) is a quantum mechanics (QM)-based model
      designed to accurately describe intermolecular interactions. Hybrid QM/EFP
      calculations combine quantum mechanical methods with an EFP embedding to study
      complex systems in which many-body effects are relevant. As in EFP-only
      calculations, non-bonded interactions between the QM region and EFP fragments are
      computed as a sum of electrostatic, polarization, dispersion, and exchange
      repulsion energies. The exchange-repulsion term is a computational bottleneck of
      the EFP calculations. Here, we present a general procedure for computing the
      QM/EFP exchange-repulsion interactions based on one-electron contributions to the
      QM Hamiltonian, by using Gaussian functions to represent localized molecular
      orbitals of the effective fragments. The accuracy of the exchange-repulsion and
      total QM/EFP interaction energies is evaluated on a diverse set of dimers,
      including complexes from the S22 dataset of non-covalent interactions. In most
      cases, the QM/EFP energies are at least as accurate as corresponding EFP
      energies. A simple and computationally efficient form of the introduced QM/EFP
      exchange-repulsion term will facilitate further developments and applications of
      QM/EFP methods.

PMID- 30195306
TI  - Affinity, kinetics, and pathways of anisotropic ligands binding to hydrophobic
      model pockets.
AB  - Using explicit-water molecular dynamics simulations of a generic pocket-ligand
      model, we investigate how chemical and shape anisotropy of small ligands
      influences the affinities, kinetic rates, and pathways for their association with
      hydrophobic binding sites. In particular, we investigate aromatic compounds, all
      of similar molecular size, but distinct by various hydrophilic or hydrophobic
      residues. We demonstrate that the most hydrophobic sections are in general
      desolvated primarily upon binding to the cavity, suggesting that specific
      hydration of the different chemical units can steer the orientation pathways via
      a "hydrophobic torque." Moreover, we find that ligands with bimodal orientation
      fluctuations have significantly increased kinetic barriers for binding compared
      to the kinetic barriers previously observed for spherical ligands due to
      translational fluctuations. We exemplify that these kinetic barriers, which are
      ligand specific, impact both binding and unbinding times for which we observe
      considerable differences between our studied ligands.

PMID- 30195307
TI  - Dissipative particle dynamics modeling of hydrogel swelling by osmotic ensemble
      method.
AB  - An osmotic ensemble method for dissipative particle dynamics (DPD) is developed
      for simulating the swelling behavior of polymer networks in aqueous solvent under
      constant solvent chemical potential, number of polymer beads, pressure, and
      temperature conditions. We apply a Langevin piston method to control the pressure
      of the polymer-solvent mixture. Chemical potential equilibrium is achieved via
      Monte Carlo insertions and deletions of solvent beads based on the total free
      energy change of the gel. The osmotic ensemble simulation produces swelling
      kinetics of hydrogels in excellent agreement with that obtained by previous
      methods but significantly reduces computational costs. The results show gel
      swelling as a result of the mechanical balance between osmotic pressure induced
      by the mixing of the polymer and solvent and elastic force originated from the
      network deformation. The simulations also elucidate the influence of solvent
      conditions and network topology on the degree of swelling. The bulk modulus of
      the model gel is probed at different solvency and its behavior is consistent with
      the prediction of Flory-Rehner theory. The osmotic ensemble DPD will permit the
      study of mechanical properties of hydrogels in mesoscale simulations and can be
      extended to model other complex fluid systems in chemical equilibrium under
      isothermal-isobaric conditions.

PMID- 30195308
TI  - Communication: Multidimensional triple sum-frequency spectroscopy of MoS2 and
      comparisons with absorption and second harmonic generation spectroscopies.
AB  - Triple sum-frequency (TSF) spectroscopy is a recently developed methodology that
      enables collection of multidimensional spectra by resonantly exciting multiple
      quantum coherences of vibrational and electronic states. This work reports the
      first application of TSF to the electronic states of semiconductors. Two
      independently tunable ultrafast pulses excite the A, B, and C features of a MoS2
      thin film. The measured TSF spectrum differs markedly from absorption and second
      harmonic generation spectra. The differences arise because of the relative
      importance of transition moments and the joint density of states (JDOS). We
      develop a simple model and globally fit the absorption and harmonic generation
      spectra to extract the JDOS and the transition moments from these spectra. Our
      results validate previous assignments of the C feature to a large JDOS created by
      band nesting.

PMID- 30195309
TI  - Finite-size corrections in numerical simulation of liquid water.
AB  - Monte Carlo (MC) simulations of the SPC/E liquid water model are performed at two
      numbers of molecules N = 100 and 512 and in canonical NVT, isobaric NPT, and
      grand canonical MUVT ensembles. The molecular non-spherically symmetric pair
      distribution function g(r, Omega) (pdf) is accumulated in terms of projections
      gMUnumnl(r) onto rotational invariants. The precisely measured differences
      between N values and between ensembles are in very good agreement with the
      theoretical predictions for the expected finite-size corrections of different
      origins: (1) the canonical simulation is affected by explicit corrections due to
      the absence of density fluctuations. Beyond the well-known shift in the long
      range asymptote, all projections exhibit rich short-range contributions. These
      corrections vanish exactly in the isobaric ensemble provided that the pdf is
      constructed using the rigorous definition. (2) In the presence of dielectric
      discontinuity with the external medium surrounding the central box and its
      replica within the Ewald treatment of the Coulombic interactions, the
      disagreement with the prediction of the literature, already noticed recently for
      dipolar fluids, is confirmed in the present site-site model. (3) The implicit
      corrections originate from the coupling between the environment around a given
      particle and that around its periodic images in the neighboring cells. The
      recent, powerful MC/HNC mixed integral equation, which offers a complete and
      exact description of the molecular correlations in the whole real and Fourier
      spaces, enables us to quantify the observed N-dependence in the pdf projections
      down to the sub 10-3 levels.

PMID- 30195311
TI  - Modeling the effects of molecular disorder on the properties of Frenkel excitons
      in organic molecular semiconductors.
AB  - The Frenkel exciton model provides a convenient framework for simulating
      electronic excitations in organic conjugated systems that are too large to
      address with atomistic level electronic structure methods. Parameterization of
      this model is typically based on analytical expressions that incompletely
      describe the spatial and temporal correlations that are inherent to many
      condensed phase molecular systems. In this manuscript, we present a general
      procedure for including these correlations in the Frenkel exciton model, by
      mapping them directly from all-atom molecular configurations, for instance from
      classical molecular dynamics. Regardless of system morphology, this mapping
      automatically captures the spatial and temporal molecular correlations that are
      otherwise difficult or impossible to represent in terms of low-dimensional
      correlation functions. We apply this procedure to study the excited state
      properties of condensed phase materials made up of thiophene oligomers. We show
      that Frenkel model parameters can be mapped from a series of single molecule
      electronic structure calculations, and that for these materials efficient semi
      empirical methods are sufficient to accurately reproduce experimental spectral
      measurements. By analyzing the statistics of model parameters derived from
      materials with different characteristic morphologies, we highlight failures in
      some assumptions that are commonly applied when generating model parameters.
      Finally, by simulating exciton dynamics on a mapped Frenekel exciton model, we
      demonstrate the ability to quantify the effect of material morphology on the
      dynamic properties of excitons.

PMID- 30195310
TI  - Rheological consequences of wet and dry friction in a dumbbell model with
      hydrodynamic interactions and internal viscosity.
AB  - The effect of fluctuating internal viscosity and hydrodynamic interactions on a
      range of rheological properties of dilute polymer solutions is examined using a
      finitely extensible dumbbell model for a polymer. Brownian dynamics simulations
      are used to compute both transient and steady state viscometric functions in
      shear flow. The results enable a careful differentiation of the influence, on
      rheological properties, of solvent-mediated friction from that of a dissipative
      mechanism that is independent of solvent viscosity. In particular, hydrodynamic
      interactions have a significant influence on the magnitude of the stress jump at
      the inception of shear flow, and on the transient viscometric functions, but a
      negligible effect on the steady state viscometric functions at high shear rates.
      Zero-shear rate viscometric functions of free-draining dumbbells remain
      essentially independent of the internal viscosity parameter, as predicted by the
      Gaussian approximation, but the inclusion of hydrodynamic interactions induces a
      dependence on both the hydrodynamic interaction and the internal viscosity
      parameter. Large values of the internal viscosity parameter lead to linear
      viscoelastic predictions that mimic the behavior of rigid dumbbell solutions. On
      the other hand, steady-shear viscometric functions at high shear rates differ in
      general from those for rigid dumbbells, depending crucially on the finite
      extensibility of the dumbbell spring.

PMID- 30195312
TI  - Assessment and optimization of collective variables for protein conformational
      landscape: GB1 beta-hairpin as a case study.
AB  - Collective variables (CVs), when chosen judiciously, can play an important role
      in recognizing rate-limiting processes and rare events in any biomolecular
      systems. However, high dimensionality and inherent complexities associated with
      such biochemical systems render the identification of an optimal CV a challenging
      task, which in turn precludes the elucidation of an underlying conformational
      landscape in sufficient details. In this context, a relevant model system is
      presented by a 16-residue beta-hairpin of GB1 protein. Despite being the target
      of numerous theoretical and computational studies for understanding the protein
      folding, the set of CVs optimally characterizing the conformational landscape of
      the beta-hairpin of GB1 protein has remained elusive, resulting in a lack of
      consensus on its folding mechanism. Here we address this by proposing a pair of
      optimal CVs which can resolve the underlying free energy landscape of the GB1
      hairpin quite efficiently. Expressed as a linear combination of a number of
      traditional CVs, the optimal CV for this system is derived by employing the
      recently introduced time-structured independent component analysis approach on a
      large number of independent unbiased simulations. By projecting the replica
      exchange simulated trajectories along these pair of optimized CVs, the resulting
      free energy landscape of this system is able to resolve four distinct well
      separated metastable states encompassing the extensive ensembles of folded,
      unfolded, and molten globule states. Importantly, the optimized CVs were found to
      be capable of automatically recovering a novel partial helical state of this
      protein, without needing to explicitly invoke helicity as a constituent CV.
      Furthermore, a quantitative sensitivity analysis of each constituent in the
      optimized CV provided key insights on the relative contributions of the
      constituent CVs in the overall free energy landscapes. Finally, the kinetic
      pathways connecting these metastable states, constructed using a Markov state
      model, provide an optimum description of the underlying folding mechanism of the
      peptide. Taken together, this work offers a quantitatively robust approach toward
      comprehensive mapping of the underlying folding landscape of a quintessential
      model system along its optimized CV.

PMID- 30195313
TI  - Viscosity and self-diffusion of supercooled and stretched water from molecular
      dynamics simulations.
AB  - Among the numerous anomalies of water, the acceleration of dynamics under
      pressure is particularly puzzling. Whereas the diffusivity anomaly observed in
      experiments has been reproduced in several computer studies, the parallel
      viscosity anomaly has received less attention. Here we simulate viscosity and the
      self-diffusion coefficient of the TIP4P/2005 water model over a broad temperature
      and pressure range. We reproduce the experimental behavior and find additional
      anomalies at negative pressure. The anomalous effect of pressure on dynamic
      properties becomes more pronounced upon cooling, reaching two orders of magnitude
      for viscosity at 220 K. We analyze our results with a dynamic extension of a
      thermodynamic two-state model, an approach which has proved successful in
      describing experimental data. Water is regarded as a mixture of interconverting
      species with contrasting dynamic behaviors, one being strong (Arrhenius) and the
      other fragile (non-Arrhenius). The dynamic parameters of the two-state models are
      remarkably close between experiment and simulations. The larger pressure range
      accessible to simulations suggests a modification of the dynamic two-state model,
      which in turn also improves the agreement with experimental data. Furthermore,
      our simulations demonstrate the decoupling between viscosity eta and self
      diffusion coefficient D as a function of temperature T. The Stokes-Einstein
      relation, which predicts a constant Deta/T, is violated when T is lowered, in
      connection with the Widom line defined by an equal fraction of the two
      interconverting species. These results provide a unifying picture of
      thermodynamics and dynamics in water and call for experiments at negative
      pressure.

PMID- 30195314
TI  - Identifying complex Fermi resonances in p-difluorobenzene using zero-electron
      kinetic-energy (ZEKE) spectroscopy.
AB  - The vibrations of the ground state cation ( X2B2g) of para-difluorobenzene (pDFB)
      have been investigated using zero-electron-kinetic-energy (ZEKE) spectroscopy. A
      comprehensive set of ZEKE spectra were recorded via different vibrational levels
      of the S1 state (<00 + 1300 cm-1). The adiabatic ionization energy for pDFB was
      measured as 73 869 +/- 5 cm-1. Use of different intermediate levels allows
      different cationic vibrational activity to be obtained via the modification of
      the Franck-Condon factors for the ionization step, allowing the wavenumbers of
      different vibrational levels in the cation to be established. In addition,
      assignment of the vibrational structure in the ZEKE spectra allowed interrogation
      of the assignments of the S1 <- S0 transition put forward by Knight and Kable [J.
      Chem. Phys. 89, 7139 (1988)]. Assignment of the vibrational structure has been
      aided by quantum chemical calculations. In this way, it was possible to assign
      seventeen of the thirty vibrational modes of the ground state pDFB+ cation.
      Evidence for complex Fermi resonances in the S1 state, i.e., those that involve
      more than two vibrations, was established. One of these was investigated using
      picosecond time-resolved photoelectron spectroscopy. In addition, we discuss the
      appearance of several symmetry-forbidden bands in the ZEKE spectra, attributing
      their appearance to a Rydberg state variation of an intrachannel vibronic
      coupling mechanism.

PMID- 30195315
TI  - Auger electron angular distributions following excitation or ionization of the I
      3d level in methyl iodide.
AB  - Auger electron spectra following excitation or ionization of the I 3d level in
      CH3I have been recorded with horizontally or vertically plane polarized
      synchrotron radiation. These spectra have enabled the Auger electron angular
      distributions, as characterized by the beta parameter, to be determined. The I 3d
      photoionization partial cross section of CH3I has been calculated with the
      continuum multiple scattering approach, and the results show that in the photon
      energy range over which Auger spectra were measured, the I 3d cross section
      exhibits an atomic-like behavior and is dominated by transitions into the
      epsilonf continuum channel. In this limit, the theoretical value of the alignment
      parameter (A20) characterizing the core ionized state in an atom becomes
      constant, independent of photon energy. This theoretical value has been used to
      obtain the Auger electron intrinsic anisotropy parameters (alpha2) from the beta
      parameters extracted from our normal (non-resonant) molecular Auger spectra. The
      resulting anisotropy parameters for the M45N45N45 transitions in CH3I have been
      compared to those calculated for the corresponding transitions in xenon, and the
      experimental and theoretical results are in good agreement. Anisotropy parameters
      have also been measured for the M45N1N45, M45N23N45, and M45N45O23 transitions.
      For the M45N1N45 and M45N23N45 Auger decays in CH3I, the experimentally derived
      angular distributions do not exhibit the strong dependence on the final ionic
      state that is predicted for these transitions in xenon. Resonantly excited Auger
      spectra have been recorded at 620.4 and 632.0 eV, coinciding with the I 3d5/2 ->
      sigma* and 3d3/2 -> sigma* transitions, respectively. The resulting Auger
      electron angular distributions for the M4N45N45 and M5N45N45 decays were found to
      exhibit a higher anisotropy than those for the normal process. This is due to the
      larger photo-induced alignment in the neutral core excited state. For a
      particular Auger transition, the Auger electron kinetic energy measured in the
      resonantly excited spectrum is higher than that in the normal spectrum. This
      shift, due to the screening provided by the electron excited into the sigma*
      orbital, has been rationalized by calculating orbital ionization energies of I 3d
      excited and I 3d ionized states in CH3I.

PMID- 30195316
TI  - Non-Markovian decoherence dynamics in nonequilibrium environments.
AB  - We theoretically investigate the non-Markovian dynamical decoherence of a quantum
      system coupled to nonequilibrium environments with nonstationary statistical
      properties. We show the time evolution of the decoherence factor in real
      imaginary space to study the environment-induced energy renormalization and
      backaction of coherence which are associated with the unitary and nonunitary
      parts of the quantum master equation, respectively. It is also shown that the
      nonequilibrium decoherence dynamics displays a transition between Markovian and
      non-Markovian and the transition boundary depends on the environmental
      parameters. The results are helpful for further understanding non-Markovian
      dynamics and coherence backaction on an open quantum system from environments.

PMID- 30195317
TI  - Discrete discontinuous basis projection method for large-scale electronic
      structure calculations.
AB  - We present an approach to accelerate real-space electronic structure methods
      several fold, without loss of accuracy, by reducing the dimension of the discrete
      eigenproblem that must be solved. To accomplish this, we construct an efficient,
      systematically improvable, discontinuous basis spanning the occupied subspace and
      project the real-space Hamiltonian onto the span. In calculations on a range of
      systems, we find that accurate energies and forces are obtained with 8-25 basis
      functions per atom, reducing the dimension of the associated real-space
      eigenproblems by 1-3 orders of magnitude.

PMID- 30195318
TI  - Glass forming phase diagram and local structure of Kob-Andersen binary Lennard
      Jones nanoparticles.
AB  - Molecular dynamics simulation is used to study glass formation in Kob-Andersen
      binary Lennard-Jones nanoparticles and determine the glass forming phase diagram
      for the system as a function of composition. The radial distribution function, a
      Steinhardt bond-orientational order parameter, and favored local structure
      analysis are used to distinguish between glassy and ordered systems. We find that
      surface enrichment of the large atoms alters the nanoparticle core composition,
      leading to an overall shift of the glass forming region to lower small atom mole
      fractions, relative to the bulk system. At small atom mole fraction, xB = 0.1,
      the nanoparticles form a solid with an amorphous core, enriched with the small
      atoms, surrounded by a partially ordered surface region, enriched with the large
      atom component. The most disordered glass nanoparticles occur at xB ~ 0.3, but
      the surface-core enrichment leads to the crystallization of the nanoparticle to
      the CsCl crystal above xB ~ 0.35, which is lower than observed in the bulk. The
      glass transition temperatures of the nanoparticles are also significantly
      reduced. This allows the liquid to remain dynamic to low temperatures and sample
      the low energy inherent structure minima on the potential energy surface
      containing a high abundance of favoured local structures.

PMID- 30195319
TI  - Methane on a stepped surface: Dynamical insights on the dissociation of CHD3 on
      Pt(111) and Pt(211).
AB  - The simulation of the dissociation of molecules on metal surfaces is a
      cornerstone for the understanding of heterogeneously catalyzed processes.
      However, due to high computational demand, the accurate dynamical simulation of
      the dissociative chemisorption of polyatomic molecules has been limited mostly to
      flat low-index metal surfaces. The study of surfaces that feature "defected"
      sites, such as steps, is crucial to improve the understanding of the overall
      catalytic process due to the high reactivity of under-coordinated sites for this
      kind of reaction. In this work, we have extensively analyzed more than 10 000 ab
      initio molecular dynamics trajectories where a CHD3 molecule is impinging either
      on the flat Pt(111) surface or on the stepped Pt(211) surface for different
      initial rovibrational states and collision energies. The results have been
      compared in order to get insight into the effect of the step in the dissociation
      of methane. We have found that, despite a large difference in the activation
      barrier and consequently in reactivity, the geometry of the lowest transition
      states is very similar on the two surfaces and this results in a similar
      dissociation dynamics. Furthermore, the trapping observed on the Pt(211) surface
      can be explained with energy transfer to parallel translational motion induced by
      the geometry of the slab and by a larger energy transfer to phonons for the
      stepped Pt(211) surface.

PMID- 30195320
TI  - Adaptation of Skeletal Muscles to Contractile Activity of Varying Duration and
      Intensity: The Role of PGC-1alpha.
AB  - A large body of experimental data have shown that aerobic exercise of different
      duration, intensity, and pattern affect molecular mechanisms regulating
      mitochondrial biogenesis in skeletal muscles. This review focuses on the effects
      of exercise duration and intensity on the molecular mechanisms of mitochondrial
      biogenesis regulation in skeletal muscles, namely PGC-1alpha-dependent signaling.
      Studies of the effects of acute exercise and exercise training showed that an
      increase in the duration of aerobic exercise from 30 to 90 min does not provide
      additional stimuli to activate signaling pathways regulating post-translational
      modification of peroxisome proliferator-activated receptor gamma coactivator
      1alpha (PGC-1alpha) and expression of the PGC-1alpha gene (PPARGC1A). Conversely,
      exercise intensity substantially affects mitochondrial biogenesis due to the
      increase in the recruitment of type II muscle fibers with accompanying pronounced
      metabolic shift leading to the activation of signaling cascades and expression of
      genes regulating mitochondrial biogenesis. Therefore, intermittent exercise,
      which recruits type II muscle fibers, is more efficient in the activation of
      mitochondrial biogenesis than work-matched continuous exercise. In skeletal
      muscle adapted to aerobic training, intensity-dependent activation of
      mitochondrial biogenesis after acute exercise is associated primarily with the
      AMP-activated protein kinase/PGC-1alpha pathway, expression of PGC-1alpha
      regulated genes, and expression of PPARGC1A from the alternative (distal)
      inducible promoter regulated by the cAMP response element-binding protein 1
      related transcription factors and their coactivators. Elucidation of the effects
      of duration and intensity of aerobic exercise on the PGC-1alpha-dependent and 
      independent mechanisms of mitochondrial biogenesis is important for treatment of
      patients with various metabolic disorders, as well as for optimization of
      training in athletes.

PMID- 30195321
TI  - Practical Recommendations for Improving Efficiency and Accuracy of the
      CRISPR/Cas9 Genome Editing System.
AB  - CRISPR/Cas9 genome-editing system is a powerful, fairly accurate, and efficient
      tool for modifying genomic DNA. Despite obvious advantages, it is not devoid of
      certain drawbacks, such as propensity for introduction of additional nonspecific
      DNA breaks, insufficient activity against aneuploid genomes, and relative
      difficulty in delivering its components to cells. In this review, we focus on the
      difficulties that can limit the use of CRISPR/Cas9 and suggest a number of
      practical recommendations and information sources that will make it easier for
      the beginners to work with this outstanding technological achievement of the XXI
      century.

PMID- 30195322
TI  - Import of Proteins and Nucleic Acids into Mitochondria.
AB  - Many mitochondrial genes have been transferred to the nucleus in course of
      evolution. The products of expression of these genes, being still necessary for
      organelle function, are imported there from the cytosol. Molecular mechanisms of
      protein import are studied much deeper than those of nucleic acids. The latter,
      it seems to us, retards the development of mitochondrial genome editing
      technologies. In this review, we describe mechanisms of DNA, RNA, and protein
      import into mitochondria of different eukaryotes. The description is given for
      the natural processes, as well as for artificial targeting of macromolecules into
      mitochondria for therapy. Also, we discuss different approaches to introduce
      changes into the mitochondrial DNA sequence.

PMID- 30195323
TI  - Aureochromes - Blue Light Receptors.
AB  - A variety of living organisms including bacteria, fungi, animals, and plants use
      blue light (BL) to adapt to changing ambient light. Photosynthetic forms (plants
      and algae) require energy of light for photosynthesis, movements, development,
      and regulation of activity. Several complex light-sensitive systems evolved in
      eukaryotic cells to use the information of light efficiently with photoreceptors
      selectively absorbing various segments of the solar spectrum, being the first
      components in the light signal transduction chain. They are most diverse in
      algae. Photosynthetic stramenopiles, which received chloroplasts from red algae
      during secondary symbiosis, play an important role in ecosystems and aquaculture,
      being primary producers. These taxa acquired the ability to use BL for regulation
      of such processes as phototropism, chloroplast photo-relocation movement, and
      photomorphogenesis. A new type of BL receptor - aureochrome (AUREO) - was
      identified in Vaucheria frigida in 2007. AUREO consists of two domains: bZIP
      (basic-region leucine zipper) domain and LOV (light-oxygen-voltage-sensing)
      domain, and thus this photoreceptor is a BL-sensitive transcription factor. This
      review presents current data on the structure, mechanisms of action, and
      biochemical features of aureochromes.

PMID- 30195324
TI  - Calcineurin and Its Role in Synaptic Transmission.
AB  - Calcineurin (CaN) is a serine/threonine phosphatase widely expressed in different
      cell types and structures including neurons and synapses. The most studied role
      of CaN is its involvement in the functioning of postsynaptic structures of
      central synapses. The role of CaN in the presynaptic structures of central and
      peripheral synapses is less understood, although it has generated a considerable
      interest and is a subject of a growing number of studies. The regulatory role of
      CaN in synaptic vesicle endocytosis in the synapse terminals is actively studied.
      In recent years, new targets of CaN have been identified and its role in the
      regulation of enzymes and neurotransmitter secretion in peripheral neuromuscular
      junctions has been revealed. CaN is the only phosphatase that requires calcium
      and calmodulin for activation. In this review, we present details of CaN
      molecular structure and give a detailed description of possible mechanisms of CaN
      activation involving calcium, enzymes, and endogenous and exogenous inhibitors.
      Known and newly discovered CaN targets at pre- and postsynaptic levels are
      described. CaN activity in synaptic structures is discussed in terms of
      functional involvement of this phosphatase in synaptic transmission and
      neurotransmitter release.

PMID- 30195325
TI  - Mobility of Nuclear Components and Genome Functioning.
AB  - Cell nucleus is characterized by strong compartmentalization of structural
      components in its three-dimensional space. Certain genomic functions are
      accompanied by changes in the localization of chromatin loci and nuclear bodies.
      Here we review recent data on the mobility of nuclear components and the role of
      this mobility in genome functioning.

PMID- 30195326
TI  - Structural Study of the Complex Formed by Ceruloplasmin and Macrophage Migration
      Inhibitory Factor.
AB  - Macrophage migration inhibitory factor (MIF) is a key proinflammatory cytokine.
      Inhibitors of tautomerase activity of MIF are perspective antiinflammatory
      compounds. Ceruloplasmin, the copper-containing ferroxidase of blood plasma, is a
      noncompetitive inhibitor of tautomerase activity of MIF in the reaction with p
      hydroxyphenylpyruvate. Small-angle X-ray scattering established a model of the
      complex formed by MIF and ceruloplasmin. Crystallographic analysis of MIF with a
      modified active site supports the model. The stoichiometry of 3 CP/MIF trimer
      complex was established using gel filtration. Conformity of novel data concerning
      the interaction regions in the studied proteins with previous biochemical data is
      discussed.

PMID- 30195327
TI  - Construction of Artificial TNF-Binding Proteins Based on the 10th Human
      Fibronectin Type III Domain Using Bacterial Display.
AB  - Construction of antibody mimetics on the base of alternative scaffold proteins is
      a promising strategy for obtaining new products for medicine and biotechnology.
      The aim of our work was to optimize the cell display system for the 10th human
      fibronectin type III domain (10Fn3) scaffold protein based on the AT877
      autotransporter from Psychrobacter cryohalolentis K5T and to construct new
      artificial TNF-binding proteins. We obtained a 10Fn3 gene combinatorial library
      and screened it using the bacterial display method. After expression of the
      selected 10Fn3 variants in Escherichia coli cells and analysis of their TNF
      binding activity, we identified proteins that display high affinity for TNF and
      characterized their properties.

PMID- 30195328
TI  - Rhamnose-Containing Cell Wall Glycopolymers from Rathayibacter toxicus VKM Ac
      1600 and "Rathayibacter tanaceti" VKM Ac-2596.
AB  - Structures of the cell wall glycopolymers from two representatives of the genus
      Rathayibacter were investigated using chemical, NMR spectroscopy, and optical
      methods. The R. toxicus VKM Ac-1600 strain contains two neutral glycopolymers - a
      linear rhamnomannan ->2)-alpha-D-Rhap-(1->3)-alpha-D-Manp-(1-> and a branched
      polysaccharide containing in the repeating unit the residues of D-Manp, D-Glcp,
      and L-Rhap in the ratios of 2 : 4 : 1, respectively (the structure is presented
      in the text). The "Rathayibacter tanaceti" VKM Ac-2596 contains a rhamnomannan
      that is different from the above-described one by localization of glycosidic
      bonds on the residues of alpha-Rhap and alpha-Manp, i.e. ->3)-alpha-D-Rhap (1->2)
      alpha-D-Manp-(1->. The structures of all identified glycopolymers are described
      for the first time in actinobacteria. The data obtained make it possible to
      characterize representatives of the studied actinobacteria more fully and can be
      used to differentiate Rathayibacter species at the phenotype level.

PMID- 30195329
TI  - Localization of Galectins within Glycocalyx.
AB  - Galectins are involved in various biological processes, e.g. cell-cell and cell
      matrix adhesion and the transmission of cellular signals. Despite the diversity
      of functions, little is known about the nature of their physiological cognate
      ligands on the cell surface and the localization of galectins in the glycocalyx,
      although this information is important for understanding the functional activity
      of galectins. In this work, localization of endogenous and exogenously loaded
      galectins in the glycocalyx was studied. The following main conclusions are
      drawn: 1) galectins are not evenly distributed within the glycocalyx, they are
      accumulated in patches. Patching is not the result of a cross-linking of cellular
      glycans by galectins. Instead, patch-wise localization is the consequence of
      irregular distribution of glycans forming the glycocalyx; 2) galectins are
      accumulated in the inner zone of the glycocalyx rather than at its outer face or
      directly in vicinity of the cell membrane; 3) patches are not associated with
      cell rafts.

PMID- 30195330
TI  - Implication of Integrin alpha2beta1 in Proliferation and Invasion of Human Breast
      Carcinoma and Melanoma Cells: Noncanonical Function of Akt Protein Kinase.
AB  - Blocking the expression of integrin alpha2beta1, which was accomplished by
      transduction of alpha2-specific shRNA, resulted in significant inhibition of
      proliferation and clonal activity in human MCF-7 breast carcinoma and SK-Mel-147
      melanoma cells. Along with these changes, deprivation of alpha2beta1 caused a
      sharp decrease in melanoma cell invasion in vitro. Analysis of integrin-mediating
      signal pathways that control cell behavior revealed a significant increase in
      activity of Akt protein kinase in response to depletion of alpha2beta1. The
      increase in Akt activity that accompanies a suppressive effect on cell invasion
      contradicts well-known Akt function aimed at stimulation of tumor progression.
      This contradiction could be explained by the "reversed" (noncanonical) role
      played by Akt in some cells that consists in suppression rather than promotion of
      invasive phenotype. To test this suggestion, the effects of Akt inhibitors on
      invasive activity of SK-Mel-147 cells were investigated. If the above suggestion
      is true, then inhibition of Akt in cells depleted of alpha2beta1 should result in
      the restoration of their invasive activity. It appeared that treatment with
      LY294002, which inhibits all Akt isoforms (Akt1, Akt2, Akt3), not only failed to
      restore the invasive phenotype of melanoma cells but further attenuated their
      invasive activity. However, treatment of the cells with an Akt1-specific
      inhibitor significantly increased their invasion. Thus, the stimulating effect of
      alpha2beta1 integrin on invasion of melanoma cells is realized through a
      mechanism based on inhibition of one of the Akt isoforms, which in these cells
      exhibits a noncanonical function consisting in suppression of invasion.

PMID- 30195331
TI  - The Role of p38 and CK2 Protein Kinases in the Response of RAW 264.7 Macrophages
      to Lipopolysaccharide.
AB  - The role of protein kinases p38 and CK2 (casein kinase II) in the response of RAW
      264.7 macrophages to the lipopolysaccharide (LPS) from gram-negative bacteria was
      studied. Using specific p38 and CK2 inhibitors (p38 MAP kinase Inhibitor XI and
      casein kinase II Inhibitor III, respectively), we investigated the effects of
      these protein kinases on (i) LPS-induced activation of signaling pathways
      involving nuclear factor kappaB (NF-kappaB), stress-activated protein kinase/c
      Jun N-terminal kinase (SAPK/JNK), p38, and interferon regulatory factor 3 (IRF3);
      (ii) expression of Toll-like receptor 4 (TLR4) and inducible heat-shock proteins
      HSP72 and HSP90; and (iii) production of interleukins IL-1alpha, IL-1beta, IL-6,
      tumor necrosis factor alpha, and IL-10. Activation of the proapoptotic signaling
      in the macrophages was evaluated from the ratio between the active and inactive
      caspase-3 forms and p53 phosphorylation. Six hours after LPS addition (2.5
      MUg/ml) to RAW 264.7 cells, activation of the TLR4 signaling pathways was
      observed that was accompanied by a significant increase in phosphorylation of
      IkappaB kinase alpha/beta, NF-kappaB (at both Ser536 and Ser276), p38, JNK, and
      IRF3. Other effects of macrophage incubation with LPS were an increase in the
      contents of TLR4, inducible heat-shock proteins (HSPs), and pro- and anti
      inflammatory cytokines, as well as slight activation of the pro-apoptotic
      signaling in the cells. Using inhibitor analysis, we found that during the early
      response of macrophages to the LPS, both CK2 and p38 modulate activation of MAP
      kinase and NF-kappaB signaling pathways and p65 phosphorylation at Ser276/Ser536
      and cause accumulation of HSP72, HSP90 and the LPS-recognizing receptor TLR4.
      Suppression of the p38 MAP kinase and CK2 activities by specific inhibitors
      (Inhibitor XI and Inhibitor III, respectively) resulted in the impairment of the
      macrophage effector function manifested as a decrease in the production of the
      early-response proinflammatory cytokines and disbalance between the pro- and anti
      apoptotic signaling pathways leading presumably to apoptosis development. Taken
      together, our data indicate the inefficiency of therapeutic application of p38
      and CK2 inhibitors during the early stages of inflammatory response.

PMID- 30195333
TI  - Identification and Characterization of MicroRNAs in Skin of Chinese Giant
      Salamander (Andrias davidianus) by the Deep Sequencing Approach.
AB  - MicroRNAs (miRNA) play a pivotal role in regulating a broad range of biological
      processes, acting by cleaving mRNAs or by translational repression. However, the
      miRNAs from skin of Andrias davidianus have not been reported. In this study, a
      small-RNA cDNA library was constructed and sequenced from skin of A. davidianus.
      A total of 513 conserved miRNAs belonging to 174 families were identified. The
      remaining 108 miRNAs we identified were novel and likely to be skin tissue
      specific but were expressed at low levels. The presence of randomly selected 15
      miRNAs identified and their expression in eight different tissues from A.
      davidianus were validated by stem-loop qRT-PCR. For better understanding the
      functions of miRNAs, 129,791 predicated target genes were analyzed by GO and
      their pathways illustrated by KEGG pathway analyses. The results show that these
      identified miRNAs from A. davidianus skin are involved in a broad range of
      physiological functions including metabolism, growth, development, and immune
      responses. This study exhaustively identifies miRNAs and their target genes,
      which will ultimately pave the way for understanding their role in skin of A.
      davidianus and other amphibians. Further studies are necessary to better
      understand miRNA-mediated gene regulation.

PMID- 30195332
TI  - Transgenic Arabidopsis Plants Expressing Grape Glutathione S-Transferase Gene
      (VvGSTF13) Show Enhanced Tolerance to Abiotic Stress.
AB  - Although glutathione S-transferase (GST, EC 2.5.1.18) is thought to play
      important roles in abiotic stress, limited information is available regarding the
      function of its gene in grapes. In this study, a GST gene from grape, VvGSTF13,
      was cloned and functionally characterized. Transgenic Arabidopsis plants
      containing this gene were normal in terms of growth and maturity compared with
      control plants but had enhanced resistance to salt, drought, and methyl viologen
      stress. The increased tolerance of the transgenic plants correlated with changes
      in activities of antioxidative enzymes. Our results indicate that the gene from
      grape plays a positive role in improving tolerance to salinity, drought, and
      methyl viologen stresses in Arabidopsis.

PMID- 30195334
TI  - Inflammatory myofibroblastic tumor of the pleura with adjacent chest wall
      invasion and metastasis to the kidney: a case report.
AB  - BACKGROUND: Inflammatory myofibroblastic tumor is a rare benign neoplasm that
      frequently involves the lung and abdominopelvic region, and is found mainly in
      children and young adults. Inflammatory myofibroblastic tumor tends to be locally
      invasive or recurrent, and rarely metastasizes. CASE PRESENTATION: A 76-year-old
      Korean man presented with a history of upper back pain for 2 months and motor
      weakness in both lower extremities for 2 days. Contrast-enhanced computed
      tomography of his chest and abdomen showed a large heterogeneous pleural mass
      involving the right fifth rib and vertebral body and a mass infiltrating the
      right renal hilum. Computed tomography-guided percutaneous needle biopsy of the
      pleural mass was performed. The histological findings on hematoxylin and eosin
      staining showed proliferation of spindle cells with infiltration of lymphocytes
      and plasma cells. Immunohistochemistry showed neoplastic cells positive for CD68,
      focally positive for smooth muscle actin, and negative for cytokeratin and
      desmin. Inflammatory myofibroblastic tumor was diagnosed based on the
      histological examination. Treatment with glucocorticoids (methylprednisolone 1
      mg/kg) and radiotherapy (5 days/week for 3 weeks at 3 Gy/fraction, 45 Gy/15 days)
      was started. After 1 month, chest computed tomography showed a reduction in the
      size of the pleural mass, and abdominopelvic computed tomography showed decreased
      infiltration around the right renal pelvis. CONCLUSIONS: Inflammatory
      myofibroblastic tumor is a rare neoplasm of intermediate malignant potential due
      to a tendency for local recurrence and it rarely develops distant metastases.
      Complete surgical resection is the primary treatment. However, unresectable and
      metastatic inflammatory myofibroblastic tumor can be treated with systemic
      therapy, including glucocorticoids, radiotherapy, and/or chemotherapy.

PMID- 30195336
TI  - Biomarkers in Pulmonary Nodule Diagnosis: Is It Time to Put Away the Biopsy
      Needle?

PMID- 30195337
TI  - In Search of the Holy Grail: Evidence-Based, Patient-Focused, Safe Care for VTE.

PMID- 30195335
TI  - Prospective observational cohort study of 'treatment as usual' over four years
      for patients with schizophrenia in a national forensic hospital.
AB  - BACKGROUND: We evaluated change in response to multi-modal psychosocial
      'treatment as usual' programs offered within a forensic hospital. METHODS: Sixty
      nine patients with a diagnosis of schizophrenia or schizoaffective disorder were
      followed for up to four years. Patient progress was evaluated using the DUNDRUM
      3, a measure of patient ability to participate and benefit from multi-modal
      psychosocial programs and the HCR-20 dynamic items, a measure of violence
      proneness. We report reliable change index (RCI) and reliable and clinically
      meaningful change (RMC). We assessed patients' cognition using the MCCB,
      psychopathology using the PANSS. The effect of cognition and psychopathology on
      change in DUNDRUM-3 was examined using hierarchical multiple regression with age,
      gender, and baseline DUNDRUM-3 scores. RESULTS: The DUNDRUM-3 changed
      significantly (p < 0.004, d = 0.367, RCI 32% of 69 cases, RMC 23%) and HCR-20-C
      (p < 0.003, d = 0.377, RCI 10%). Both cognition and psychopathology accounted for
      significant variance in DUNDRUM-3 at follow up. Those hospitalized for less than
      five years at baseline changed more than longer stay patients. Mediation analysis
      demonstrated that the relationship between cognition and change in violence
      proneness (HCR-20-C) was both directly affected and indirectly mediated by change
      in DUNDRUM-3. CONCLUSIONS: Change in response to multi-modal psychosocial
      programs (DUNDRUM-3) reduced a measure of violence proneness over four years.
      Forensic in-patients' ability to benefit from psychosocial treatment appears to
      be a function of the outcome measure used, unit of measurement employed, degree
      of cognitive impairment, psychopathology, and length of stay. Lower risk of re
      offending may be partially attributable to participation and engagement in
      psychosocial interventions.

PMID- 30195338
TI  - Machine Learning for Treating Complicated Parapneumonic Effusions: The
      Fundamentals Still Apply.

PMID- 30195339
TI  - COPD in China: From Crisis to Hope....

PMID- 30195340
TI  - Giants in Chest Medicine: Douglas J. Mathisen, MD.

PMID- 30195342
TI  - COUNTERPOINT: Should Computerized Protocols Replace Physicians for Managing
      Mechanical Ventilation? No.

PMID- 30195341
TI  - POINT: Should Computerized Protocols Replace Physicians for Managing Mechanical
      Ventilation? Yes.

PMID- 30195343
TI  - Rebuttal From Drs Grissom and Brown.

PMID- 30195345
TI  - Last Tango.

PMID- 30195344
TI  - Rebuttal From Dr MacIntyre.

PMID- 30195346
TI  - Visiting Hours.

PMID- 30195348
TI  - Tattoos.

PMID- 30195347
TI  - Parts and Service.

PMID- 30195349
TI  - Should Patients With Interstitial Lung Disease Be Seen by Experts?

PMID- 30195350
TI  - Response.

PMID- 30195351
TI  - Reservations Regarding Lung Cancer Screening Guidelines.

PMID- 30195352
TI  - Response.

PMID- 30195353
TI  - Activity and Outcomes From a Dedicated Pleural On-Call Service.

PMID- 30195354
TI  - Effect of Statins on Sepsis Outcome in a Population-Based Cohort Study.

PMID- 30195355
TI  - Response.

PMID- 30195356
TI  - Features of COPD as Predictors of Lung Cancer.

PMID- 30195357
TI  - Response.

PMID- 30195358
TI  - Multiplex PCR on the Bronchoalveolar Lavage Fluid of Immunocompromised Patients.

PMID- 30195359
TI  - Pigtail Catheter vs Chest Tube as the Initial Treatment for Pneumothorax.

PMID- 30195360
TI  - Impact of Particulate Matter on the Natural History of IPF: A Matter of
      Concentrations?

PMID- 30195361
TI  - Response.

PMID- 30195362
TI  - Response.

PMID- 30195363
TI  - Size Does Matter: Calculation of Tidal Volume Using Weight Estimations From the
      PAWPER Tape.

PMID- 30195364
TI  - Response.

PMID- 30195365
TI  - Tai Chi Recreational Exercise Is Not Rehabilitation.

PMID- 30195366
TI  - Response.

PMID- 30195367
TI  - Tai Chi Is Not Equivalent to Pulmonary Rehabilitation.

PMID- 30195368
TI  - Response.

PMID- 30195369
TI  - Unique Obstacles for Mentorship During Training.

PMID- 30195370
TI  - Response.

PMID- 30195371
TI  - Between a Rock and an Airspace: Pneumothorax After Extracorporeal Shock Wave
      Lithotripsy for Renal Stones in a Patient With Cystic Fibrosis.
AB  - Renal disease is a well-recognized manifestation of cystic fibrosis (CF) and
      people with CF are at increased risk of nephrolithiasis. Lithotripsy is the
      preferred treatment but has occasionally been associated with pulmonary
      complications. Here we report the case of a person with CF who developed a
      pneumothorax soon after lithotripsy and discuss the potential mechanism of
      injury. We hope this case highlights some of the additional considerations
      clinicians should take into account when managing patients with advanced
      pulmonary disease in CF.

PMID- 30195372
TI  - A 33-Year-Old Woman With Progressive Dyspnea and Fatigue.

PMID- 30195373
TI  - A 39-Year-Old Man With Diabetes, Pleuritic Chest Pain, and Multiple Cavitary Lung
      Nodules.
AB  - CASE PRESENTATION: A 39-year-old male presented to the ED with a 2-day history of
      fever (Temperature-Maximum 39 degrees C), nonbloody productive cough, and
      worsening right-sided pleuritic chest pain. The patient denied shortness of
      breath, nausea, vomiting, sinus symptoms, and abdominal pain. His medical history
      included type 2 diabetes mellitus (glycated hemoglobin, 11.1), hyperlipidemia,
      and depression. He smoked marijuana but denied tobacco or illicit drug use. He
      reported no recent travels. He reported a 1-week history of left molar pain that
      began after he siphoned stagnant water with a straw from a refrigerator drip pan.
      He lived in Ohio all of his life. He denied any sick contacts. His medications
      include Lantus insulin at night, metformin, glimepiride, pravastatin, and
      Remeron.

PMID- 30195374
TI  - A 47-Year-Old Man With Progressive Mental Deterioration During Ventilator
      Management of Asthma in the ICU.
AB  - CASE PRESENTATION: A 47-year-old man was admitted to the ICU with acute
      hypercapnic respiratory failure caused by a severe asthma attack. He had a
      history of asthma, atrial septal defect, chronic heart failure, and atrial
      fibrillation. He underwent surgical closure of the atrial septal defect at 7
      years of age and was asymptomatic until 38 years of age when he developed
      congestive heart failure because of structural cardiac abnormalities, including
      left ventricular systolic dysfunction, biatrial enlargement, and mild mitral and
      tricuspid regurgitation. After ICU admission, he received ventilator management
      for asthma, IV prednisone, beta-2 agonist via inhalation, and ceftriaxone.
      Enteral feeding was provided since the day of admission. Hypercapnia gradually
      improved over 3 days. He remained alert and could communicate through writing
      during ventilator management until the third day in the ICU. Enteral feeding was
      titrated up to 32 kcal/kg/d with 1.6 g/kg/d of protein. Despite the recovery from
      the initial respiratory failure, he became inactive and lethargic on the fourth
      day in the ICU. ICU-acquired delirium was suspected, and administration of
      sedatives and analgesics was discontinued. On the following day, he was
      unresponsive to stimuli.

PMID- 30195375
TI  - A 48-Year-Old Man With Multiple Pulmonary Nodular Opacities and Elevated KL-6
      Level.
AB  - CASE PRESENTATION: A 48-year-old man was referred for evaluation of an abnormal
      chest shadow noted on a routine chest radiograph during physical examination. He
      was asymptomatic and had no significant medical history and occupational
      exposure. The patient lived in Tokyo and had no significant travel history. He
      had smoked approximately 20 cigarettes daily for 20 years. He had no illicit drug
      use and no animal-rearing history.

PMID- 30195376
TI  - A 63-Year-Old Man Presents With Slowly Progressive Dyspnea on Exertion and Lower
      Extremity Muscle Weakness.
AB  - CASE PRESENTATION: A 63-year-old man was referred for slowly progressive dyspnea
      on exertion that had developed over 7 years. Dyspnea was initially only present
      during high-intensity physical activity, but was now present while walking
      rapidly on a flat surface. Symptoms were accentuated while supine and when
      bending forward. He reported respiratory difficulties when submerged in water and
      a recent onset of slight symmetric lower limb weakness that was only apparent
      during strenuous physical activity. He also had OSA, which was adequately
      controlled with continuous positive airway pressure therapy. Neurologic and
      rheumatologic histories were otherwise unremarkable. He denied any impact
      accidents or trauma to the cervical spine and prior neck or thoracic surgeries.

PMID- 30195377
TI  - A translational perspective on epigenetics in allergic diseases.
AB  - The analysis of epigenetic modifications in allergic diseases has recently
      attracted substantial interest because epigenetic modifications can mediate the
      effects of the environment on the development of or protection from allergic
      diseases. Furthermore, recent research has provided evidence for an altered
      epigenomic landscape in disease-relevant cell populations. Although still in the
      early phase, epigenetic modifications, particularly DNA methylation and
      microRNAs, might have potential for assisting in the stratification of patients
      for treatment and complement or replace in the future biochemical or clinical
      tests. The first epigenetic biomarkers correlating with the successful outcome of
      immunotherapy have been reported, and with personalized treatment options being
      rolled out, epigenetic modifications might well play a role in monitoring or even
      predicting the response to tailored therapy. However, further studies in larger
      cohorts with well-defined phenotypes in specific cell populations need to be
      performed before their implementation. Furthermore, the epigenome provides an
      interesting target for therapeutic intervention, with microRNA mimics,
      inhibitors, and antisense oligonucleotides being evaluated in clinical trials in
      patients with other diseases. Selection or engineering of populations of
      extracellular vesicles and epigenetic editing represent novel tools for
      modulation of the cellular phenotype and responses, although further
      technological improvements are required. Moreover, interactions between the host
      epigenome and the microbiome are increasingly recognized, and interventions of
      the microbiome could contribute to modulation of the epigenome with a potential
      effect on the overall goal of prevention of allergic diseases.

PMID- 30195378
TI  - Epigenetic mechanisms regulating T-cell responses.
AB  - During the last decade, advances in sequencing technologies allowed production of
      a wealth of information on epigenetic modifications in T cells. Epigenome maps,
      in combination with mechanistic studies, have demonstrated that T cells undergo
      extensive epigenome remodeling in response to signals, which has a strong effect
      on phenotypic stability and function of lymphocytes. In this review we focus on
      DNA methylation, histone modifications, and chromatin structure as important
      epigenetic mechanisms involved in controlling T-cell responses. In particular, we
      discuss epigenetic processes in light of the development, activation, and
      differentiation of CD4+ T helper (TH), regulatory T, and CD8+ T cells. As central
      aspects of the adaptive immune system, we review mechanisms that ensure molecular
      memory, stability, plasticity, and exhaustion of T cells. We further discuss the
      effect of the tissue environment on imprinting T-cell epigenomes with potential
      implications for immunotherapy.

PMID- 30195380
TI  - Retraction notice to "The effectiveness of group-based behavioral activation in
      the treatment of depression: an updated meta-analysis of randomized controlled
      trial" [JAD 208 (2017) 345-l354].

PMID- 30195381
TI  - A myosin5 dsRNA that reduces the fungicide resistance and pathogenicity of
      Fusarium asiaticum.
AB  - Fungal resistance to fungicides is a serious challenge in crop protection.
      Although strategies have been found to prevent the development of fungicide
      resistance, rare strategy has been found to quickly reduce such resistance once
      it has occurred. We demonstrate that the application of dsRNAs, which inhibit the
      expression of the phenamacril (fungicide JS399-19) target gene-Myosin 5 (Myo5) in
      Fusarium, decreased F. asiaticum resistance to phenamacril and infection. RNAi
      molecules derived from different regions of Myo5 gene had different effects on
      phenamacril-resistance. Myo5-8 (one of Myo5 segments) exhibited great and stable
      effect on phenamacril-resistant reduction both in vivo and in vitro. Myo5 mRNA
      and protein were both reduced when mycelium was treated with Myo5-8 dsRNA. After
      a mixture of Myo5-8 dsRNA and phenamacril treatment, plants can highly control
      the infection of phenamacril-resistant strain. The antifungal activity of Myo5-8
      dsRNA plus phenamacril effected longer than a single Myo5-8 dsRNA. In addition,
      no off-target sequences were found in wheat and/or other plant and animal species
      for Myo5-8 dsRNA sequence. Our findings suggest a new strategy for fungicide
      resistant reduction and for designing new fungicides to control pathogens which
      easily develop fungicide resistance.

PMID- 30195382
TI  - Action of selenium against Sclerotinia sclerotiorum: Damaging membrane system and
      interfering with metabolism.
AB  - Selenium (Se) in soil is beneficial for environmental stress tolerance of plants,
      and it has widespread toxic effects on pathogens. Based on the fact that Se
      significantly inhibited the growth of Sclerotinia sclerotiorum, we set
      experiments with different concentrations of Se to investigate the action of Se
      against S. sclerotiorum in this study. The results showed that Se (>0.5 mg L-1)
      changed the morphology of S. sclerotiorum mycelia, and higher Se concentrations
      severely damaged mycelial structures. Fourier transform infrared spectroscopy
      (FTIR) analysis indicated that Se treatment induced the chemical composition of
      mycelia with much abundance of functional groups such as alcohols, ketones,
      ammonium and esters, and 0.5 mg L-1 Se maximized their concentrations. Under Se
      treatments, the electrical conductivity of mycelia increased in a time-dependent
      manner, and osmolyte concentrations of mycelia increased as well. Se
      supplementation significantly reduced polymethylgalacturonase (PMG) and
      carboxymethylcellulase (Cx) activities, which protecting plants from infection,
      and increased the energy expenditure in S. sclerotiorum. Combined action of Se
      damage on membrane system, osmoregulation, reduction of cell wall degrading
      enzymes activities and improvement of energy expenditure resulted in the
      inhibition of S. sclerotiorum growth. Findings in this study provided evidences
      for using Se as a potential fungicide to control S. sclerotiorum.

PMID- 30195383
TI  - Mechanisms of resistance to thiamethoxam and dinotefuran compared to imidacloprid
      in the brown planthopper: Roles of cytochrome P450 monooxygenase and a P450 gene
      CYP6ER1.
AB  - The brown planthopper (BPH, Nilaparvata lugens) has developed high resistance to
      the first-generation neonicotinoids (imidacloprid). With commercialization and
      widespread field use of the second-(thiamethoxam) and third-(dinotefuran)
      generation neonicotinoids, resistance to these insecticides is also reported. We
      investigated the cytochrome P450 monooxygenase-mediated detoxification in
      thiamethoxam- and dinotefuran- resistant in comparison to imidacloprid-resistant
      strains of BPH. In the three moderately resistant BPH strains selected separately
      with the three insecticides from a same susceptible strain, P450 activities were
      significantly enhanced over the susceptible control. Seven of 26 tested P450
      genes were up-regulated and CYP6ER1 was a strongly over-expressed gene in all the
      three resistant strains. Knockdown of CYP6ER1 in the susceptible insects reduced
      P450 activity, retarded nymph growth and significantly increased sensitivity to
      each one of the three neonicotinoids. Taken together, we show that enhanced P450
      activity and over-expression of CYP6ER1 gene are involved in BPH resistance to
      thiamethoxam and dinotefuran as to imidacloprid. These findings are of
      significance in management thiamethoxam and dinotefuran resistance in the BPH,
      especially in the management of potential cross-resistance to the three
      generations of neonicotinoids.

PMID- 30195384
TI  - Plant-derived compounds regulate formation of the insect juvenile hormone
      receptor complex.
AB  - Insect growth regulators (IGRs) are attractive pest control agents due to their
      high target specificity and relative safety to the environment. Recently, plants
      have been shown to synthesize IGRs that affect the insect juvenile hormone (JH)
      as a part of their defense mechanisms. Using a yeast two-hybrid system
      transformed with the Aedes aegypti JH receptor as a reporter system, we
      identified several JH agonists (JHAs) and antagonists (JHANs) causing retardation
      in the ovarian development of female Asian tiger mosquito, Aedes albopictus, from
      plant essential oil compounds. While the JHAs increased the expression of a JH
      induced gene, the JHANs caused a reduction in the expression of the same gene.
      The compounds identified in this study could provide insights into plant-insect
      interactions and may be useful for the development of novel IGR insecticides.

PMID- 30195385
TI  - Molecular cloning and characterization of GABA receptor and GluCl subunits in the
      western flower thrips, Frankliniella occidentalis.
AB  - To understand the role of target site insensitivity in abamectin resistance in
      the western flower thrips (WFT), Frankliniella occidentalis (Pergande), cDNAs
      encoding gamma-aminobutyric acid receptor subunit (FoRdl) and glutamate-gated
      chloride channel (FoGluCl) were cloned from WFT, and both single nucleotide
      polymorphisms (SNPs) and mRNA expression levels of FoRdl and FoGluCl were
      detected in a susceptible strain (ABA-S) and a laboratory selected strain (ABA-R)
      displaying 45.5-fold resistance to abamectin. Multiple cDNA sequence alignment
      revealed three alternative splicing variants of FoRdl and two alternative
      splicing variants of FoGluCl generated by alternative splicing of exon 3. While
      sequence comparison of FoRdl and FoGluCl in ABA-S and ABA-R strains identified no
      resistance-associated mutations, the expression level of FoGluCl in ABA-R strain
      was 2.63-fold higher than that in ABA-S strain. Thus, our preliminary results
      provide the evidence that the increased mRNA expression of FoGluCl could be an
      important factor in FoGluCl-mediated target site insensitivity in WFT.

PMID- 30195387
TI  - Diazinon exposure activated transcriptional factors CCAAT-enhancer-binding
      proteins alpha (C/EBPalpha) and peroxisome proliferator-activated receptor gamma
      (PPARgamma) and induced adipogenesis in 3T3-L1 preadipocytes.
AB  - Environmental chemical exposure could be a contributor to the increasing obesity
      epidemic. Diazinon, an organophosphate insecticide, has been widely used in the
      agriculture, and exposure of the general population to diazinon has been
      reported. Diazinon has been known to induce neurotoxic effects mainly through the
      inhibition of acetylcholinesterase (AChE). However, its association with
      dysregulation of adipogenesis has been poorly investigated. The current study
      aimed to examine the mechanism of diazinon's effect on adipogenesis using the 3T3
      L1 preadipocytes combined with a single-cell-based high-content analysis. The
      results showed that diazinon induced lipid droplet accumulation in a dose
      dependent manner. The dynamic changes of adipogenic regulatory proteins and genes
      were examined at the three stages of adipogenesis (induction, differentiation,
      and maturation) in 3T3-L1 cells treated with various doses of diazinon (0, 1, 10,
      100 MUM) using real-time quantitative RT-PCR and Western Blot respectively.
      Diazinon significantly induced protein expression of transcriptional factors
      CCAAT-enhancer-binding proteins alpha (C/EBPalpha) and peroxisome proliferator
      activated receptor gamma (PPARgamma), their downstream proteins, fatty acid
      synthase (FASN), acetyl CoA carboxylase (ACC), fatty acid-binding protein 4
      (FABP4), lipoprotein lipase (LPL), adiponectin and perilipin in dose and time
      dependent manners. Similarly, the adipogenic genes were significantly induced in
      a dose and time-dependent manner compared to the relative controls. The current
      study demonstrates that diazinon promotes lipid accumulation and activates the
      adipogenic signaling pathway in the in vitro model.

PMID- 30195386
TI  - Effects of alpha-pinene, trans-anethole, and thymol as the essential oil
      constituents on antioxidant system and acetylcholine esterase of Ephestia
      kuehniella Zeller (Lepidoptera: Pyralidae).
AB  - The current study aimed to determine the potential effects of three essential oil
      constituents, alpha-pinene, trans-anethole, and thymol, on antioxidant system and
      acetylcholine esterase (AChE) of Ephestia kuehniella Zeller. The 4th instar
      larvae were initially fed on an artificial diet containing an LC50 concentration
      of each above-mentioned compounds separately prior to being undertaken for sample
      preparation and biochemical assays. The significant higher activities of
      superoxide dismutase, peroxidase and catalase were observed in the treated-larvae
      at both time intervals. Similar findings were found in the activity of
      glutathione S-transferase by using both reagents. Although activities of
      ascorbate peroxidase and glycerol-6-phosphate dehydrogenase increased in the
      treated larvae by all constituents while glycerol-6-phosphate dehydrogenase
      showed no statistically different activity among the larvae fed on alpha-pinene,
      trans-anethole, and thymol. The concentration of malondialdehyde and the ratio of
      oxidized (RSSR) to reduced (RSH) thiols showed statistical differences among
      control and treated larvae except for time interval of 24 h regarding the ratio
      of RSSR/RSH. Finally, our results demonstrated a significant decrease of AChE
      activity in the treated larvae by all constituents after 24 h while no
      statistical differences were found between control and trans-anethole after 24 h.
      Also, in vitro analysis revealed significant inhibition of AChE representing IC50
      values of 0.864, 0.490 and 0.137 MUl/ml for alpha-pinene, trans-anethole, and
      thymol, respectively. These results determined significant effects of
      administered constituents on induction of antioxidant system and inhibition of a
      nervous system component which expand our knowledge on physiological turbulences
      due to essential oil treatment.

PMID- 30195388
TI  - Notopterygium incisum extract and associated secondary metabolites inhibit apple
      fruit fungal pathogens.
AB  - In the search for antifungal lead compounds from natural resources, Notopterygium
      incisum, a medicine plant only distributed in China, showed antifungal potential
      against apple fruit pathogens. Based on the bioassay-guided isolation,
      chromatography fraction 6 of the ethyl acetate partition exhibited significant in
      vitro and in vivo antifungal activities against apple fruit pathogens.
      Furthermore, nine antifungal secondary metabolites, including five linear
      furocoumarins (1-5), two phenylethyl esters (6-7), one falcarindiol (8), and one
      sesquiterpenoid (9), were isolated and elucidated from fraction 6. Compound 5 is
      a new metabolite, and 9 isolated from the genus Notopterygium for the first time.
      The purified compounds (1-9) were firstly reported to exhibit antifungal
      activities against apple fruit pathogens of Colletotrichum gloeosporioides and
      Botryosphaeria dothidea with the MIC values ranging from 8 to 250 mg L-1,
      especially 8 of 16 and 8 mg L-1, respectively. Moreover, 8 could inhibit the
      spore germination and new sporulation of B. dothidea, as well as enhance the
      membrane permeabilization of B. dothidea spores. This was the first investigation
      for the antifungal components against apple fruit pathogens from Notopterygium
      incisum, which has great potential to be developed into bio-fungicides.

PMID- 30195389
TI  - Rapid and persistent RNAi response in western corn rootworm adults.
AB  - RNA interference (RNAi) has proven effective for controlling pest insects such as
      western corn rootworm (WCR), Diabrotica virgifera virgifera (Coleoptera:
      Chrysomelidae). Previous studies have shown that WCR adults display a robust RNAi
      response to orally-administered double-stranded RNA (dsRNA). However, it is
      unclear how quickly the response occurs after ingestion or how long RNAi effect
      lasts after WCR stop ingesting diet containing dsRNA. In the current study, WCR
      adult females were provided with diet treated with dsRNAs of Laccase 2 and
      Argonaute 2, two nonessential genes, for 8 days. RNAi response in WCR females
      commenced as early as 10 h after exposure to dsRNA and lasted up to 40 days after
      exposure to dsRNA ended. Our results show that dsRNA-mediated RNAi response in
      WCR females is rapid and long-lasting. These findings suggest that even a short
      term ingestion of transgenic plants expressing dsRNA by WCR may have a sustained
      impact on this insect.

PMID- 30195390
TI  - Effects of azinphos-methyl on enzymatic activity and cellular immune response in
      the hemolymph of the freshwater snail Chilina gibbosa.
AB  - The use of a battery of biomarkers, especially those more closely related to
      species integrity, is desired for more complete ecotoxicological assessments of
      the effects of pesticide contamination on aquatic organisms. The
      phosphorodithioate azinphos-methyl has been intensively used in agriculture
      worldwide and have been found in the habitat of Chilina gibbosa, a freshwater
      snail endemic to South America. This snail has been proposed as a good model
      organism for ecotoxicity bioassays on the basis of studies focused mainly on
      enzymatic responses in whole tissue homogenates. Our aim was to evaluate the
      effect of an acute 48 h exposure to an environmental concentration of azinphos
      methyl on C. gibbosa hemolymph enzymatic activity and cellular immune response.
      Our results show that cholinesterase activity was strongly inhibited (94%) in
      hemolymph of exposed snails. Carboxylesterase activity measured with p
      nitrophenyl butyrate and glutathione S-transferase activity were augmented 47%
      and 89% respectively after exposure. No differences were found for hemolymph
      carboxylesterase activity measured with p-nitrophenyl acetate. These results
      differ from those reported for whole tissue homogenates and reveal that tissue
      specific responses of enzymatic biomarkers exist in this species. Regarding
      immune cell response, hemocytes were identified for the first time for C.
      gibbosa. Their viability and phagocytic activity decreased after azinphos-methyl
      exposure although total number of circulating cells did not differ between
      treatments. We conclude that concentrations of azinphos-methyl that can be found
      in the environment can compromise both hemolymph cholinesterase activity and the
      immune system of C. gibbosa. Furthermore, we propose that carboxylesterase and
      glutathione S-transferase activities measured in hemolymph and hemocyte viability
      and phagocytic activity could be incorporated as sensitive biomarkers to evaluate
      the effects of pesticide exposure on this and related species.

PMID- 30195391
TI  - Identification of a small antimycotic peptide produced by Bacillus
      amyloliquefaciens 6256.
AB  - Bacillus sp. 6256 is a good biocontrol agent against Botrytis cinerea which
      caused tomato gray mold disease. Strain 6256 was identified as B.
      amyloliquefaciens by analysis of its partial gyrB gene sequence. To identify and
      characterize the antimycotic peptides from the culture broth of the bacterium,
      the antimicrobial substances produced by B. amyloliquefaciens 6256 were isolated
      by ammonium sulfate precipitation, Superdex 200 gel filtration chromatography and
      DEAE anion exchange chromatography. The purified compound was designated as P657.
      The biological activity of P657 was stable at as high as 100  degrees C for 20
      min and in pH value ranged from 5 to 10. The antimycotic compound was resistant
      to trypsin and proteinase K, and could completely inhibit spore germination of
      Botrytis cinerea in vitro. MALDI-TOF-MS analysis results showed the presence of
      fengycins A (C16-C17) and fengycins B (C15-C17) isoforms in P657.

PMID- 30195392
TI  - Mesotrione herbicide does not cause genotoxicity, but modulates the genotoxic
      effects of Atrazine when assessed in mixture using a plant test system (Allium
      cepa).
AB  - Mesotrione (MES) is an herbicide from the triketone family and has been used as
      an alternative to Atrazine (ATZ), which was banned in some countries due to its
      toxicity to non-target organisms. Despite being considered an eco-friendly
      herbicide, data from the literature about the harmful effects of MES in its pure
      form and/or in combination with other herbicides is still scarce. Aimed at
      assessing the potential of MES to induce cell death and DNA damage, seeds of
      Allium cepa (higher plant, monocotyledon) were exposed to this herbicide, pure
      and in mixture with ATZ, and the number of dividing cells (cytotoxicity),
      chromosomal aberrations (CA, genotoxicity) and micronuclei (MN, mutagenicity)
      were then quantified. The pure MES (1.8 to 460 MUg/L) did not show either
      cytotoxicity or genotoxicity/mutagenicity under the tested conditions. The
      genotoxicity of ATZ (1.5 to 400 MUg/L), previous reported in the literature, was
      confirmed herein. The assessment of MES + ATZ mixtures (1.8 + 1.5; 7 + 6.25; 30 +
      25 MUg/L, respectively) showed that MES, at low concentrations, enhance the
      genotoxicity of ATZ (potentiation), since the significant frequencies of CA and
      MN were greater than the ones expected in additive effects. Taking together, MES
      in its pure form seems to be a safe alternative to ATZ regarding the capacity to
      damage (at cellular and DNA levels) non-target plants (Monocots); however, MES in
      combination with ATZ appeared to act as a co-mutagen at low concentrations.

PMID- 30195393
TI  - Status of pesticide resistance and associated mutations in the two-spotted spider
      mite, Tetranychus urticae, in China.
AB  - The two-spotted spider mite, Tetranychus urticae Koch, is a serious agricultural
      pest that has developed resistance to many pesticides. A leaf dip assay was used
      to assess the resistance of seven field populations of T. urticae to 11
      pesticides in China. The mutation frequencies of target genes related to
      pesticide resistance were also determined. The results showed that all seven
      field populations had high or extremely high resistance to abamectin and had low
      or moderate resistance to newly developed pesticides including bifenazate,
      cyenopyrafen, chlorfenapyr, B-azolemiteacrylic, and spinetoram. The RF values for
      the traditional acaricides bifenthrin, pyridaben, and profenofos were low for all
      seven populations. For target sites related to abamectin resistance, the
      frequency of the mutations ranged from 28.33 to 63.64% for G314D in the glutamate
      gated chloride channel gene 1 (GluCl1), and from 0 to 95% for G326E in the
      glutamate-gated chloride channel gene 3 (GluCl3). For target sites related to
      organophosphate resistance, the frequency of mutations ranged from 33.33 to
      56.67% for G119S and from 5.00 to 43.33% for A201S in the acetycholinesterase
      gene (Ace). For target sites related to pyrethroid resistance, the frequency of
      the mutations ranged from 76.67 to 98.33% for A1215D and from 3.33 to 100% for
      F1538I in the voltage-gated sodium channel gene (VGSC). No mutations were
      detected in the bifenazate resistance-related cytochrome b gene (Cytb). These
      results will be useful for managing T. urticae resistance to pesticides in China.

PMID- 30195394
TI  - Effects of high temperature on insecticide tolerance in whitefly Bemisia tabaci
      (Gennadius) Q biotype.
AB  - Bemisia tabaci (Gennadius) Q biotype (BTQ) has spread to many tropical and
      subtropical regions over the past several decades. This may reflect an advantage
      biotype Q has over closely related forms in having greater thermal and/or
      insecticide resistance, although the effects of higher temperatures on
      insecticide tolerance of BTQ has, to date, been largely ignored. In this study,
      the effects of elevated temperatures on BTQ's tolerance to the insecticide
      thiamethoxam were investigated. The effect on the activities of detoxifying
      enzymes [carboxylesterase (CarE), glutathione S-transferase (GST), and cytochrome
      P450 monooxygenase (P450)] and expression profiling of eleven genes of
      detoxifying enzymes were also determined. In addition, RNA interference (RNAi)
      and bioassay methods were used to further identify the function of CYP6CM1 in
      tolerance to thiamethoxam following exposure to higher temperatures. The results
      showed that elevated temperatures were responsible for causing different outcomes
      in the tolerance of BTQ to thiamethoxam: Temperatures of 35  degrees C or higher
      decreased the tolerance of BTQ to thiamethoxam, while a moderately high
      temperature of 31  degrees C increased the tolerance. The high temperature
      influenced the tolerance of BTQ by affecting the activity of P450. Quantitative
      real-time PCR (qPCR) showed that CYP6CM1 was significantly up-regulated in most
      treatments at 31  degrees C, but was suppressed at 35  degrees C, which was
      closely associated with the mortality rates. Feeding on double-stranded RNA
      (dsRNA) of CYP6CM1 significantly reduced the mRNA levels of the target gene in
      the adults, and dramatically decreased tolerance to thiamethoxam induced by a
      temperature of 31  degrees C for 6 h. Our finding provides useful information to
      better understand the invasion mechanism of BTQ.

PMID- 30195395
TI  - [Biosimilars: Yes, but with cause knowledge].

PMID- 30195396
TI  - The Impact of Gender on Atrial Fibrillation Incidence and Progression to
      Dementia.
AB  - There are a paucity of data regarding the role of gender and atrial fibrillation
      (AF) on cognitive decline and incidence of dementia. Such data may provide
      insight into the disproportionate incidence of dementia in women and may help
      identify high-risk characteristics to target for prevention. We examined patients
      who underwent coronary angiography at an Intermountain Healthcare Medical Center
      and enrolled in a prospective cardiovascular database. To be included, patients
      could not have a previous diagnosis of AF or dementia and had to have 5years of
      follow-up. Endpoints included incident AF and dementia. Study cohort consisted of
      35,608 patients without a previous history of AF or dementia, with 14,377 (40.4%)
      being woman. Women had lower rates of hypertension, diabetes, coronary artery
      disease, and prior myocardial infarction, but higher rates of prior stroke. Men
      had a higher incidence of 5-year and long-term AF. However, women trended toward
      a higher incidence of 5-year and long-term dementia and stroke compared with men.
      In all groups of patients with and without AF, prior stroke predicted cognitive
      decline. In patients without a history of or development of AF, diabetes
      significantly increased risk of dementia. Women have higher rates of dementia
      over time than men, driven by higher baseline stroke rates and nontraditional
      cardiovascular risk factors. The higher dementia rates were in the setting of
      lower AF rates. However, in both men and women who develop AF, dementia rates are
      increased and do not show gender-based differences in risk.

PMID- 30195397
TI  - Putting quality and people at the centre of health systems.

PMID- 30195399
TI  - Political and technical barriers to improving quality of health care.

PMID- 30195400
TI  - Long-term experience with diaphragm pacing for traumatic spinal cord injury:
      Early implantation should be considered.
AB  - BACKGROUND: Cervical spinal cord injury can result in catastrophic respiratory
      failure requiring mechanical ventilation with high morbidity, mortality, and
      cost. Diaphragm pacing was developed to replace/decrease mechanical ventilation.
      We report the largest long-term results in traumatic cervical spinal cord injury.
      METHODS: In this retrospective review of prospective institutional review board
      protocols, all patients underwent laparoscopic diaphragm mapping and implantation
      of electrodes for diaphragm strengthening and ventilator weaning. RESULTS: From
      2000 to 2017, 92 patients out of 486 diaphragm pacing implants met the criteria.
      The age at time of injury ranged from birth to 74 years (average: 27 years). Time
      on mechanical ventilation was an average of 47.5 months (range, 6 days to 25
      years, median = 1.58 years). Eighty-eight percent of patients achieved the
      minimum of 4 hours of pacing. Fifty-six patients (60.8%) used diaphragm pacing 24
      hours a day. Five patients had full recovery of breathing with subsequent
      diaphragm pacing removal. Median survival was 22.2 years (95% confidence
      interval: 14.0-not reached) with only 31 deaths. Subgroup analysis revealed that
      earlier diaphragm pacing implantation leads to greater 24-hour use of diaphragm
      pacing and no need for any mechanical ventilation. CONCLUSION: Diaphragm pacing
      can successfully decrease the need for mechanical ventilation in traumatic
      cervical spinal cord injury. Earlier implantation should be considered.

PMID- 30195398
TI  - Mortality due to low-quality health systems in the universal health coverage era:
      a systematic analysis of amenable deaths in 137 countries.
AB  - BACKGROUND: Universal health coverage has been proposed as a strategy to improve
      health in low-income and middle-income countries (LMICs). However, this is
      contingent on the provision of good-quality health care. We estimate the excess
      mortality for conditions targeted in the Sustainable Development Goals (SDG) that
      are amenable to health care and the portion of this excess mortality due to poor
      quality care in 137 LMICs, in which excess mortality refers to deaths that could
      have been averted in settings with strong health systems. METHODS: Using data
      from the 2016 Global Burden of Disease study, we calculated mortality amenable to
      personal health care for 61 SDG conditions by comparing case fatality between
      each LMIC with corresponding numbers from 23 high-income reference countries with
      strong health systems. We used data on health-care utilisation from population
      surveys to separately estimate the portion of amenable mortality attributable to
      non-utilisation of health care versus that attributable to receipt of poor
      quality care. FINDINGS: 15.6 million excess deaths from 61 conditions occurred in
      LMICs in 2016. After excluding deaths that could be prevented through public
      health measures, 8.6 million excess deaths were amenable to health care of which
      5.0 million were estimated to be due to receipt of poor-quality care and 3.6
      million were due to non-utilisation of health care. Poor quality of health care
      was a major driver of excess mortality across conditions, from cardiovascular
      disease and injuries to neonatal and communicable disorders. INTERPRETATION:
      Universal health coverage for SDG conditions could avert 8.6 million deaths per
      year but only if expansion of service coverage is accompanied by investments into
      high-quality health systems. FUNDING: Bill & Melinda Gates Foundation.

PMID- 30195401
TI  - Enhanced recovery after abdominal wall reconstruction reduces length of
      postoperative stay: An observational cohort study.
AB  - BACKGROUND: Enhanced recovery after surgery has been shown to lead to improved
      postoperative outcomes after several surgical procedures. However, only a few
      studies have examined the application of enhanced recovery after surgery after
      abdominal wall reconstruction. The aim of the current observational cohort study
      was to evaluate the outcomes of enhanced recovery after surgery after abdominal
      wall reconstruction in a large cohort. METHOD: This was a retrospective cohort
      study comparing patients undergoing abdominal wall reconstruction in a standard
      care pathway (control group) with patients undergoing abdominal wall
      reconstruction in an enhanced recovery after surgery pathway. Registered outcomes
      included 30-day postoperative complications, length of stay, and readmission
      rate. RESULTS: A total of 190 patients undergoing abdominal wall reconstruction
      for large incisional hernias were included in the study, of which 96 were treated
      according to standard protocol, and 94 underwent enhanced recovery after surgery
      pathway. Length of stay was significantly reduced after the introduction of
      enhanced recovery after surgery (median 4, interquartile range 3-6 days vs.
      control 5, 4-7 days, P < .001). There was no difference between the cohorts in
      the incidence of postoperative complications requiring operative intervention
      (enhanced recovery after surgery 10.6% vs control 10.4%, P = 1.0) or the rate of
      readmissions (enhanced recovery after surgery 16.0% vs control 12.5%, P = .635).
      CONCLUSION: Enhanced recovery after surgery is feasible after abdominal wall
      reconstruction, leading to reduced length of stay without increasing the rate of
      complications or readmissions. Enhanced recovery should be implemented as
      standard in centers performing abdominal wall reconstruction.

PMID- 30195402
TI  - Oncologic superiority of anatomic resection of hepatocellular carcinoma by
      ultrasound-guided compression of the portal tributaries compared with nonanatomic
      resection: An analysis of patients matched for tumor characteristics and liver
      function.
AB  - BACKGROUND: The superiority of anatomic resection compared with nonanatomic
      resection for hepatocellular carcinoma remains a matter of debate. Further, the
      technique for anatomic resection (dye injection) is difficult to reproduce.
      Anatomic resection using a compression technique is an easy and reversible
      procedure based on liver discoloration after ultrasound-guided compression of the
      tumor-feeding portal tributaries. We compared the oncologic efficacy of
      compression technique anatomic resection with that of nonanatomic resection.
      METHODS: Among patients with resected hepatocellular carcinoma, patients who
      underwent compression technique anatomic resection were matched 1-to-2 with
      nonanatomic resection cases based on the Child-Pugh class, Model for End-Stage
      Liver Disease score, cirrhosis, hepatocellular carcinoma number (1/>1), and
      hepatocellular carcinoma size (>30, 30-50, and >50 mm). The exclusion criteria
      were nonanatomic resection because of severe cirrhosis, major hepatectomy, 90-day
      mortality (0 compression technique anatomic resection), non-cancer-related death,
      and follow-up <12 months. A total of 47 patients who underwent compression
      technique anatomic resection were matched with 94 nonanatomic resection cases.
      RESULTS: All patients were Child-Pugh A, and 53% were cirrhotic. Liver function
      tests and signs of portal hypertension were similar between the groups. There was
      1 hepatocellular carcinoma in 81% of the patients, and the hepatocellular
      carcinoma was >=30 mm in 68%. Patients undergoing anatomic resection with
      compression had better 5-year survival (77% vs 60%; risk ratio = 0.423; P = .032;
      multivariable analysis), less local recurrences (4% vs 20%; P = .012), and better
      2-year local recurrence-free survival (94% vs 78%; P = .012). Nonlocal recurrence
      free survival was similar between the groups. The compression technique anatomic
      resection group more often had repeat radical treatment for recurrence (68% vs
      28%; P = .0004) and had better 3-year survival after recurrence (65% vs 42%; P =
      .043). CONCLUSION: Compression technique anatomic resection appears to provide a
      more complete removal of the hepatocellular carcinoma-bearing portal territory.
      Local disease control and survival are better with compression technique anatomic
      resection than with nonanatomic resection.

PMID- 30195403
TI  - The educating enigma: Does training level impact postoperative outcome in
      bariatric surgery?
AB  - BACKGROUND: Bariatric procedures are complex, and the acceptance of complications
      by the general public is exceedingly low. Using the database of the Metabolic and
      Bariatric Surgery Accreditation and Quality Improvement Program, outcomes in
      bariatric surgery were evaluated to determine the effect of trainees. METHODS:
      The following data on postoperative complications for patients undergoing
      bariatric surgery in 2015 were collected: surgical site infections, sepsis,
      urinary tract infection, duration of hospital stay, operative time, renal
      failure, pulmonary embolus, deep vein thrombosis, pneumonia, and re-operation.
      These were analyzed against presence and level of trainees, using analysis of
      variance after normalizing the data. RESULTS: Of 168,093 procedures, 125,078 were
      performed without trainees, 14,883 were performed with a fellow, and 28,132 were
      performed with a resident. Cases without trainees were 25% Roux-en-Y gastric
      bypass, 59% sleeve gastrectomy, and 16% other. Cases with fellows were 35% Roux
      en-Y gastric bypass, 51% sleeve gastrectomy, and 13% other; cases with residents
      were 27% Roux-en-Y gastric bypass, 59% sleeve gastrectomy, and 15% other. Patient
      demographics were similar. Average operative time differed between groups as
      follows: without trainees, 85 minutes; with residents, 105 minutes; and with
      fellows, 117 minutes (P < .001). Although not dramatically so, infections tended
      to be a bit more likely with fellows (2% vs 1%; P < .001), and the rate of
      urinary tract infection and hospital stay tended to be greater with either
      fellows or residents (1% vs 0%; P < .001; 2.0 days vs 2.1 days vs 1.8 days; P <
      .001, respectively). CONCLUSION: Fellow involvement resulted in the greatest
      operative times, and the rate of infections, urinary tract infections, and
      prolonged hospital stay, although statistically greater, were only mildly
      increased and of questionable clinical importance. These mild increases in
      postoperative complications may be attributed to prolonged operating room time.

PMID- 30195405
TI  - Microbial transmission in an outpatient clinic and impact of an intervention with
      an ethanol-based disinfectant.
AB  - BACKGROUND: Halting the spread of harmful microbes requires an understanding of
      their transmission via hands and fomites. Previous studies explored acute and
      long-term care environments but not outpatient clinics. Objectives of this study
      were to track microbial movement throughout an outpatient clinic and evaluate the
      impact of a disinfectant spray intervention targeting high-touch point surfaces.
      METHODS: At the start of the clinic day, a harmless viral tracer was placed onto
      2 fomites: a patient room door handle and front desk pen. Patient care, cleaning,
      and hand hygiene practices continued as usual. Facility fomites (n = 19), staff
      hands (n = 4), and patient hands (n = 3-4) were sampled after 2, 3.5, and 6
      hours. Tracer concentrations at baseline (before intervention) were evaluated 6
      hours after seeding. For the intervention trials, high-touch surfaces were
      cleaned 4 hours after seeding with an ethanol-based disinfectant and sampled 2
      hours after cleaning. RESULTS: At 2, 3.5, and 6 hours after seeding, virus was
      detected on all surfaces and hands sampled, with examination room door handles
      and nurses' station chair arms yielding the highest concentrations. Virus
      concentrations decreased by 94.1% after the disinfectant spray intervention (P =
      .001). CONCLUSIONS: Microbes spread quickly in an outpatient clinic, reaching
      maximum contamination levels 2 hours after inoculation, with the highest
      contamination on examination room door handles and nurses' station chairs. This
      study emphasizes the importance of targeted disinfection of high-touch surfaces.

PMID- 30195404
TI  - Development of a rapid and sensitive electrochemical biosensor for detection of
      human norovirus via novel specific binding peptides.
AB  - Human noroviruses cause acute foodborne gastroenteritis outbreaks worldwide. In
      this study, a highly sensitive and selective electrochemical biosensor was
      fabricated for the detection of human norovirus using novel peptides as
      recognition elements. The electrochemical biosensor was fabricated by assembling
      of eight novel peptides separately on the gold electrode and investigated their
      efficiencies for sensing human noroviruses. Among eight peptides, NoroBP peptide
      coated onto the gold electrode exhibited a high binding affinity towards human
      noroviruses, resulting a progressive decrease in current signals with increasing
      concentration of human norovirus (0-105 copies/mL). As a result, NoroBP
      nonFoul(FlexL)2-coated gold electrode acts an efficient electrochemical biosensor
      for highly selective detection of human norovirus with a detection limit of 1.7
      copies/mL, which is 3-fold lower than the reported methods. The developed
      electrochemical biosensor was successfully applied to detect human norovirus
      prepared by standard procedure from oyster, which suggests that the developed
      biosensor can be used as a very sensitive and selective point-of-care
      bioanalytical platform for the detection of human norovirus in various food
      samples.

PMID- 30195406
TI  - Secondary measures of hand hygiene performance in health care available with
      continuous electronic monitoring of individuals.
AB  - BACKGROUND: Hand hygiene (HH) compliance in health care is usually measured
      against versions of the World Health Organization's "Your 5 Moments" guidelines
      using direct observation. Such techniques result in small samples that are
      influenced by the presence of an observer. This study demonstrates that
      continuous electronic monitoring of individuals can overcome these limitations.
      METHODS: An electronic real-time prompting system collected HH data on a
      musculoskeletal rehabilitation unit for 12 weeks between October 2016 and October
      2017. Aggregate and professional group scores and the distributions of
      individuals' performance within groups were analyzed. Soiled utility room exits
      were monitored and compared with performance at patient rooms. Duration of
      patient room visits and the number of consecutive missed opportunities were
      calculated. RESULTS: Overall, 76,130 patient room and 1,448 soiled utility room
      HH opportunities were recorded from 98 health care professionals. Aggregate unit
      performance for patient and soiled utility rooms were both 67%, although
      individual compliance varied greatly. The number of hand wash events that
      occurred while inside patient rooms increased with longer visits, whereas HH
      performance at patient room exit decreased. Eighty-three percent of missed HH
      opportunities occurred as part of a series of missed events, not in isolation.
      CONCLUSIONS: Continuous collection of HH data that includes temporal, spatial,
      and personnel details provides information on actual HH practices, whereas direct
      observation or dispenser counts show only aggregate trends.

PMID- 30195407
TI  - Clinical and magnetic resonance imaging features of children, adolescents, and
      adults with a clinically isolated syndrome.
AB  - BACKGROUND: The diagnosis of multiple sclerosis (MS) both in children and adults
      is based on clinical and magnetic resonance imaging (MRI) features according to
      the McDonald criteria. Little is known about differences in the presentation
      between pre-pubertal children, adolescents, and adult patients at disease onset.
      OBJECTIVE: To compare (1) the clinical, cerebrospinal fluid (CSF), and MRI
      characteristics, and (2) the diagnostic performance of the 2010 McDonald criteria
      between pre-pubertal, adolescent, and adult patients with a clinically isolated
      syndrome (CIS). METHODS: We performed a retrospective analysis of the initial
      brain and spinal cord MRI scans from 11 pre-pubertal children, 46 adolescents,
      and 56 adults with a CIS. Furthermore, clinical, CSF characteristics, and the
      performance of the 2010 McDonald criteria were compared. RESULTS: The first inter
      attack interval tended to increase with age. With respect to MRI presentation,
      significantly fewer pre-pubertal children presented with juxtacortical and
      callosal lesions. We found no significant differences in the fulfillment of the
      2010 McDonald criteria between the groups. CONCLUSION: In this retrospective
      series, subtle differences between children, adolescents, and adults with a CIS
      were noted. Larger samples are required in order to establish distinct features
      of the different age groups.

PMID- 30195409
TI  - Passive Upper Airway Thermoregulation and High-Speed Assessment for Conventional
      versus Menthol Cigarette: Implications for Laryngeal Physiology.
AB  - PURPOSE: This investigation combined measures of upper airway temperature (UAT)
      with high-speed laryngeal imaging in an individual who smoked a filtered
      conventional and menthol cigarette to identify laryngeal vibratory differences
      with upper airway temperature change. It was hypothesized that (1) average UAT
      differences between trials would be similar with UAT change <=2 degrees C and (2)
      high-speed parameters would not differ between trials. METHOD: In a repeated
      measures design, UAT was measured continuously during smoking. High-speed
      laryngeal imaging was conducted immediately after each smoking trial and 10
      minutes post. RESULTS: Average UAT and end-inspiratory temperature during the
      menthol trial was unexpectedly low. Immediately following both trials, there was
      an increase in phase asymmetry, vibratory amplitude (greater magnitude of change
      for the nonmenthol trial), and the opening phase of the glottal cycle and a
      decrease in fundamental frequency compared to the baseline. During recovery,
      parameters returned to the baseline for the nonmenthol trial, however,
      fundamental frequency continued to be lower and vibratory amplitude continued to
      be larger at recovery for the menthol trial. The measure of oscillatory onset
      time did not change across the trials immediately post cigarette trial and during
      recovery suggesting that smoking resulted in changes in sustained vibratory
      function rather than the onset behavior. CONCLUSIONS: Preliminary findings
      suggest that continuous thermal mapping and high-speed laryngeal function
      assessment may provide new information about the manner in which laryngeal tissue
      responds to passive thermal perturbations with direct implications for laryngeal
      epithelial and skeletal muscle function. Future large-scale studies are needed to
      investigate this in detail.

PMID- 30195408
TI  - Long-term follow-up in pediatric patients with paroxysmal hypothermia (Shapiro's
      syndrome).
AB  - INTRODUCTION: Shapiro syndrome (SS) is characterized by spontaneous recurrent
      episodes of hypothermia, hyperhidrosis and corpus callosum (CC) agenesis. Less
      than 60 cases have been reported to date and the pathogenic mechanism as well as
      the prognosis of this syndrome are still debated. We describe the clinical
      features and long-term follow-up of a pediatric cohort of SS patients. METHODS:
      We collected 13 (10 novel) pediatric cases of SS and report their long-term
      follow-up and neurological outcome. RESULTS: All patients experienced recurring
      hypothermia, with body temperature below 35  degrees C during the episodes, often
      accompanied by hyperidrosis. CC agenesis was an inconstant structural feature in
      the present series (2/13 patients). Seven patients received antiepileptic drugs
      (AEDs) or other drug therapy for a mean period of 12 months. At long-term follow
      up (mean = 61 months, range: 60-96), all individuals were free from episodes of
      paroxysmal hypothermia independently from previous AED use or other drug therapy.
      CONCLUSION: Paroxysmal hypothermia, the core symptom of SS, behaved as a age
      dependent feature in our cohort, supporting a good long-term prognosis for SS. A
      prompt diagnosis of SS is crucial to avoid unnecessary diagnostic investigations.

PMID- 30195410
TI  - Does the Accuracy of Medical Diagnoses Affect Novice Listeners' Auditory
      Perceptual Judgments of Dysphonia Severity?
AB  - OBJECTIVE/HYPOTHESIS: To determine whether the presence and accuracy of a
      laryngeal medical diagnosis affects novice listeners' judgments of dysphonia.
      STUDY DESIGN: Prospective, within subjects, modified factorial experimental
      design. METHODS: Twenty-six speakers with dysphonia and four normophonic speakers
      provided speech recordings. Forty novice clinicians evaluated speech samples for
      roughness and breathiness using 100-mm visual analog scales in two conditions.
      First, speech samples were presented without diagnostic information. In the
      second condition, 50% of the speech samples were presented with the accurate
      laryngeal medical diagnosis, while the other 50% of samples were presented with
      an inaccurate (alternative) diagnosis. RESULTS: Results showed that judgments of
      dysphonia were affected by the presence of both accurate and inaccurate
      diagnoses. As expected, when compared to no known diagnosis, judgments of
      roughness significantly increased in severity when an accurate diagnostic label
      of vocal fold lesions was presented. Likewise, in comparison to no known
      diagnosis, judgments of breathiness trended toward an increase in severity when
      an accurate diagnostic label of vocal fold paralysis/paresis was presented.
      Interestingly, increases in perceived severity of dysphonia were also observed
      with the presentation of inaccurate diagnoses, with the overall effect of
      inaccurate diagnostic information being greater than accurate diagnoses.
      Specifically, increases in perceived roughness and breathiness were observed when
      inaccurate diagnoses included benign vocal fold lesion(s) and vocal fold
      paralysis/paresis. In contrast, inaccurate diagnostic labels indicating "clear
      larynx" or diagnoses other than benign vocal fold lesion(s) or paralysis/paresis
      resulted in decreased perceived roughness and breathiness severity. The magnitude
      of the differences in perceived severity between conditions was overall reduced
      for breathiness compared to roughness. CONCLUSIONS: Sources of bias such as
      knowledge and accuracy of medical diagnoses should be considered when novice
      clinicians use auditory-perceptual measures to evaluate dysphonia and measure
      treatment outcomes.

PMID- 30195411
TI  - Perceptual Clinical Features in Exercise-Induced Laryngeal Obstruction (EILO):
      Toward Improved Diagnostic Approaches.
AB  - INTRODUCTION: Athletes with exercise-induced laryngeal obstruction (EILO)
      (previously commonly referred to as paradoxical vocal fold motion disorder, or
      paradoxical vocal fold motion, among other terms) are often misdiagnosed,
      resulting in prolonged, and at times inappropriate, clinical management. The high
      prevalence of misdiagnosis is largely due to a lack of universal consensus of key
      clinical features indicating EILO and a dearth of validated quantitative
      approaches to accurately detect episodic laryngeal breathing disorders (ELBD)
      from other pathologies. Additionally, mechanisms underlying EILO clinical
      presentation are poorly understood, further confounding identification and
      management of the condition. Therefore, the objectives of this study were
      twofold. The first was to identify patient-centered perception of symptoms that
      could distinguish adolescent athletes with EILO from athletes without the
      condition, at baseline (rest) and during an exercise challenge (provocation), and
      to quantify symptom severities for use as preliminary diagnostic benchmarks. The
      second objective was to investigate the merit of one commonly proposed mechanism
      in the EILO literature-stress reactivity (temperament)-by comparing personality
      traits in athletes with and without EILO. METHODS: Twelve (12) athletes diagnosed
      with EILO and 14 healthy athletic volunteers without the condition were asked to
      rate the severity of their present symptoms using a 0-100 continuous visual
      analog scale. Participants then underwent an exercise challenge with simultaneous
      laryngoscopy and were asked to complete the same set of symptom severity ratings
      experienced during rigorous exercise. Finally, participants completed the Fear
      subscale on the early adolescent temperament questionnaire-revised (EATQ-R) to
      measure self-perceived levels of stress reactivity. RESULTS: There were
      significant group differences for inspiratory and expiratory dyspnea with
      exercise (P = 0.01). Symptoms of stridor (EILO: P = .01; control: P = .001) and
      throat tightness (EILO: P = .01, control: P = .01) were statistically different
      between rest and exercise in both groups. However, no group differences were
      found on these two parameters (P > .05). Other symptoms from the list of
      previously purported symptoms indicative of ELBD (e.g. cough, dysphonia) were
      infrequently reported in the exercise variant. Additionally, measurements of
      stress reactivity on the EATQ-R Fear subscale were similar between the two
      athletic groups. Interestingly, EATQ-R Fear Subscale scores for both groups were
      significantly higher compared to typical adolescents in the U.S. population (P <
      .001, respectively). DISCUSSION: Results suggest dyspnea severity, particularly
      when experienced during an exercise-induced ELBD (EILO) episode, is the most
      sensitive symptom parameter to distinguish individuals with EILO from those
      without the condition. These findings confirm previous literature describing
      episodic laryngeal breathing disorders in clinical cohorts. Results also showed
      symptoms of throat tightness and stridor is more prevalent during exercise,
      compared to rest. However, the level of their severity occurred variably across
      both groups of athletes and may point to a less robust indication of pathology.
      Finally, similarities to stress reactivity between the two athletic groups imply
      certain temperaments historically attributed to patients with EILO may instead
      better reflect temperaments in competitive young athletes, in general.
      CONCLUSION: Study findings highlight the importance of using normative
      comparisons in the study of episodic laryngeal breathing disorders to prevent
      overgeneralization of characteristics to clinical cohorts. Results also speak of
      the clinical utility of exercise challenge to improve specificity of EILO
      diagnosis.

PMID- 30195412
TI  - Anaemia and iron deficiency in relation to fatigue in cystic fibrosis.

PMID- 30195413
TI  - BI-RADS Category 5 Assessments at Diagnostic Breast Imaging:Outcomes Analysis
      Based on Lesion Descriptors.
AB  - RATIONALE AND OBJECTIVES: The Breast Imaging-Reporting and Data System (BI-RADS)
      atlas defines category 5 assessments as appropriate only for lesions that are
      almost certainly cancer, with a positive predictive value (PPV) of >=95%. This
      study aims to demonstrate the feasibility of classifying lesions at diagnostic
      breast imaging with sufficiently high PPV to merit category 5 assessments, and to
      identify those lesion descriptors that yield such a high PPV. MATERIALS AND
      METHODS: For this Health Insurance Portability and Accountability Act compliant
      and IRB exempt study, we reviewed diagnostic breast imaging examinations
      (mammography and/or ultrasound) assessed as highly suggestive of malignancy (BI
      RADS category 5). Pathology diagnosis was considered the gold standard. PPV3
      (biopsy performed) was calculated, and the BI-RADS descriptors for each lesion
      were analyzed. RESULTS: Among 22,564 consecutive diagnostic breast imaging
      examinations between January 2010 and September 2015, we identified 239 exams
      (1.1%) assessed as BI-RADS category 5 (mean age 62.5 years). Malignancy (invasive
      breast carcinoma and/or ductal carcinoma in situ) was diagnosed in 233
      examinations (PPV3 97.5% and 95% confidence interval: 96.2%-98.8%). The most
      common lesion types were mass (170) and calcifications (116). Of the 220
      examinations involving both mammography and ultrasound, no category 5 lesions had
      <3 suspicious BI-RADS descriptors, only three lesions had three suspicious
      descriptors, but the remaining 217 lesions (98.6%) had >=4 suspicious
      descriptors. CONCLUSION: In clinical practice, it is feasible to make BI-RADS
      category 5 assessments with the intended >=95% PPV. To justify a category 5
      assessment, at least four suspicious BI-RADS descriptors should be identified at
      the combination of diagnostic mammography and ultrasound examinations.

PMID- 30195414
TI  - Establishing a Surgical Preliminary Year in the IR Residency: Keys to Success.
AB  - The training paradigm of the interventional radiologist has quickly evolved with
      the approval of the integrated interventional radiology (IR) residency by the
      American Board of Medical Specialties and the Accreditation Council of Graduate
      Medical Education. Prior to appointment in an integrated IR program, a resident
      must complete a preliminary clinical year, which may be surgical, medical, or
      transitional. The unique procedural- and clinical-based skillset required of the
      IR resident is best aligned with a surgical preliminary year. The following is a
      review of the steps to successful creation of a surgical preliminary year based
      on a single institution's experience.

PMID- 30195415
TI  - Convolutional Neural Networks with Template-Based Data Augmentation for
      Functional Lung Image Quantification.
AB  - RATIONALE AND OBJECTIVES: We propose an automated segmentation pipeline based on
      deep learning for proton lung MRI segmentation and ventilation-based
      quantification which improves on our previously reported methodologies in terms
      of computational efficiency while demonstrating accuracy and robustness. The
      large data requirement for the proposed framework is made possible by a novel
      template-based data augmentation strategy. Supporting this work is the open
      source ANTsRNet-a growing repository of well-known deep learning architectures
      first introduced here. MATERIALS AND METHODS: Deep convolutional neural network
      (CNN) models were constructed and trained using a custom multilabel Dice metric
      loss function and a novel template-based data augmentation strategy. Training
      (including template generation and data augmentation) employed 205 proton MR
      images and 73 functional lung MRI. Evaluation was performed using data sets of
      size 63 and 40 images, respectively. RESULTS: Accuracy for CNN-based proton lung
      MRI segmentation (in terms of Dice overlap) was left lung: 0.93 +/- 0.03, right
      lung: 0.94 +/- 0.02, and whole lung: 0.94 +/- 0.02. Although slightly less
      accurate than our previously reported joint label fusion approach (left lung:
      0.95 +/- 0.02, right lung: 0.96 +/- 0.01, and whole lung: 0.96 +/- 0.01),
      processing time is <1 second per subject for the proposed approach versus ~30
      minutes per subject using joint label fusion. Accuracy for quantifying
      ventilation defects was determined based on a consensus labeling where average
      accuracy (Dice multilabel overlap of ventilation defect regions plus normal
      region) was 0.94 for the CNN method; 0.92 for our previously reported method; and
      0.90, 0.92, and 0.94 for expert readers. CONCLUSION: The proposed framework
      yields accurate automated quantification in near real time. CNNs drastically
      reduce processing time after offline model construction and demonstrate
      significant future potential for facilitating quantitative analysis of functional
      lung MRI.

PMID- 30195416
TI  - Combination of Adaptive Statistical Iterative Reconstruction-V and Lower Tube
      Voltage During Craniocervical Computed Tomographic Angiography Yields Better
      Image Quality with a Reduced Radiation Dose.
AB  - RATIONALE AND OBJECTIVES: To evaluate image quality and radiation exposure when
      using the adaptive statistical iterative reconstruction-V (ASIR-V) algorithm for
      reconstructing craniocervical computed tomographic angiography images acquired at
      100 kVp. MATERIALS AND METHODS: We randomly divided 121 patients into three
      groups: group A (conventional protocol), 120 kVp with filtered back projection;
      group B, 120 kVp with 50% ASIR-V; and group C, 100 kVp with 50% ASIR-V. All
      patients underwent scans in a 256-slice computed tomography (CT) scanner.
      Radiation dose (volume CT dose index), dose-length product, and effective dose,
      objective parameters such as arterial attenuation value, signal-to-noise ratio,
      contrast-to-noise ratio, and noise obtained at head, neck, and shoulder levels
      were compared among the groups. Subjective image quality was independently
      assessed by two radiologists, and interobserver reliability was assessed using
      kappa analysis. RESULTS: The radiation dose in group C was the lowest (p < 0.01)
      with a 40% reduction in volume CT dose index, dose-length product, and effective
      dose values compared to group A, and group C showed higher arterial attenuation
      than either group A or B (p < 0.01). Additionally, signal-to-noise ratio and
      contrast-to-noise ratio were higher and noise was lower in groups B and C than
      group A. Group C had better subjective image quality than groups A and B (p <
      0.05), and the interobserver reliability between the two radiologists was high (k
      = 0.783). CONCLUSION: Compared to the conventional protocol, using 50% ASIR-V and
      the 100 kVp protocol during craniocervical computed tomographic angiography
      yields better objective and subjective image quality at lower radiation doses.

PMID- 30195417
TI  - Early diagnosis of mild cognitive impairment and Alzheimer's with event-related
      potentials and event-related desynchronization in N-back working memory tasks.
AB  - BACKGROUND AND OBJECTIVE: In this study we investigate whether or not event
      related potentials (ERP) and/or event-related (de)synchronization (ERD/ERS) can
      be used to differentiate between 27 healthy elderly (HE), 21 subjects diagnosed
      with mild cognitive impairment (MCI) and 15 mild Alzheimer's disease (AD)
      patients. METHODS: Using 32-channel EEG recordings, we measured ERP responses to
      a three-level (N-back, N = 0,1,2) visual working memory task. We also performed
      ERD analysis over the same EEG data, dividing the full-band signal into the well
      known delta, theta, alpha, beta and gamma bands. Both ERP and ERD analyses were
      followed by cluster analysis with correction for multicomparisons whenever
      significant differences were found between groups. RESULTS: Regarding ERP (full
      band analysis), our findings have shown both patient groups (MCI and AD) with
      reduced P450 amplitude (compared to HE controls) in the execution of the non
      match 1-back task at many scalp electrodes, chiefly at parietal and centro
      parietal areas. However, no significant differences were found between MCI and AD
      in ERP analysis whatever was the task. As for sub-band analyses, ERD/ERS measures
      revealed that HE subjects elicited consistently greater alpha ERD responses than
      MCI and AD patients during the 1-back task in the match condition, with all
      differences located at frontal, central and occipital regions. Moreover, in the
      non-match condition, it was possible to distinguish between MCI and AD patients
      when they were performing the 0-back task, with MCI presenting more
      desynchronization than AD on the theta band at temporal and fronto-temporal
      areas. In summary, ERD analyses have revealed themselves more valuable than ERP,
      since they showed significant differences in all three group comparisons: HE vs.
      MCI, HE vs. AD, and MCI vs. AD. CONCLUSIONS: Based on these findings, we conclude
      that ERD responses to working memory (N-back) tasks could be useful not only for
      early MCI diagnosis or for improved AD diagnosis, but probably also for assessing
      the likelihood of MCI progression to AD, after further validated by a
      longitudinal study.

PMID- 30195418
TI  - A secure biometrics-based authentication key exchange protocol for multi-server
      TMIS using ECC.
AB  - BACKGROUND AND OBJECTIVES: Telecare Medicine Information System (TMIS) enables
      physicians to efficiently and conveniently make certain diagnoses and medical
      treatment for patients over the insecure public Internet. To ensure patients
      securely access to medicinal services, many authentication schemes have been
      proposed. Although numerous cryptographic authentication schemes for TMIS have
      been proposed with the aim to ensure data security, user privacy and
      authentication, various forms of attacks make these schemes impractical. METHODS:
      To design a truly secure and practical authentication scheme for TMIS, a new
      biometrics-based authentication key exchange protocol for multi-server TMIS
      without sharing the system private key with distributed servers is presented in
      this work. RESULTS: Our proposed protocol has perfect security features including
      mutual authentication, user anonymity, perfect forward secrecy and resisting
      various well-known attacks, and these security feathers are confirmed by the BAN
      logic and heuristic cryptanalysis, respectively. CONCLUSIONS: A secure biometrics
      based authentication key exchange protocol for multi-server TMIS is presented in
      this work, which has perfect security properties including perfect forward
      secrecy, supporting user anonymity, etc., and can withstand various attacks such
      as impersonation attack, off-line password guessing attack, etc.. Considering
      security is the most important factor for an authentication scheme, so our scheme
      is more suitable for multi-server TMIS.

PMID- 30195419
TI  - Cardiology record multi-label classification using latent Dirichlet allocation.
AB  - BACKGROUND AND OBJECTIVES: Electronic health records (EHRs) convey vast and
      valuable knowledge about dynamically changing clinical practices. Indeed,
      clinical documentation entails the inspection of massive number of records across
      hospitals and hospital sections. The goal of this study is to provide an
      efficient framework that will help clinicians explore EHRs and attain alternative
      views related to both patient-segments and diseases, like clustering and
      statistical information about the development of heart diseases (replacement of
      pacemakers, valve implantation etc.) in co-occurrence with other diseases. The
      task is challenging, dealing with lengthy health records and a high number of
      classes in a multi-label setting. METHODS: LDA is a statistical procedure
      optimized to explain a document by multinomial distributions on their latent
      topics and the topics by distributions on related words. These distributions
      allow to represent collections of texts into a continuous space enabling distance
      based associations between documents and also revealing the underlying topics.
      The topic models were assessed by means of four divergence metrics. In addition,
      we applied LDA to the task of multi-label document classification of EHRs
      according to the International Classification of Diseases 10th Clinical
      Modification (ICD-10). The set of EHRs had assigned 7 codes on average over 970
      different codes corresponding to cardiology. RESULTS: First, the discriminative
      ability of topic models was assessed using dissimilarity metrics. Nevertheless,
      there was an open question regarding the interpretability of automatically
      discovered topics. To address this issue, we explored the connection between the
      latent topics and ICD-10. EHRs were represented by means of LDA and, next,
      supervised classifiers were inferred from those representations. Given the low
      dimensional representation provided by LDA, the search was computationally
      efficient compared to symbolic approaches such as TF-IDF. The classifiers
      achieved an average AUC of 77.79. As a side contribution, with this work we
      released the software implemented in Python and R to both train and evaluate the
      models. CONCLUSIONS: Topic modeling offers a means of representing EHRs in a
      small dimensional continuous space. This representation conveys relevant
      information as hidden topics in a comprehensive manner. Moreover, in practice,
      this compact representation allowed to extract the ICD-10 codes associated to
      EHRs.

PMID- 30195420
TI  - Deep neural models for extracting entities and relationships in the new RDD
      corpus relating disabilities and rare diseases.
AB  - BACKGROUND AND OBJECTIVE: There is a huge amount of rare diseases, many of which
      have associated important disabilities. It is paramount to know in advance the
      evolution of the disease in order to limit and prevent the appearance of
      disabilities and to prepare the patient to manage the future difficulties. Rare
      disease associations are making an effort to manually collect this information,
      but it is a long process. A lot of information about the consequences of rare
      diseases is published in scientific papers, and our goal is to automatically
      extract disabilities associated with diseases from them. METHODS: This work
      presents a new corpus of abstracts from scientific papers related to rare
      diseases, which has been manually annotated with disabilities. This corpus allows
      to train machine and deep learning systems that can automatically process other
      papers, thus extracting new information about the relations between rare diseases
      and disabilities. The corpus is also annotated with negation and speculation when
      they appear affecting disabilities. The corpus has been made publicly accessible.
      RESULTS: We have devised some experiments using deep learning techniques to show
      the usefulness of the developed corpus. Specifically, we have designed a long
      short-term memory based architecture for disabilities identification, as well as
      a convolutional neural network for detecting their relationships to diseases. The
      systems designed do not need any preprocessing of the data, but only low
      dimensional vectors representing the words. CONCLUSIONS: The developed corpus
      will allow to train systems to identify disabilities in biomedical documents,
      which the current annotation systems are not able to detect. The system could
      also be trained to detect relationships between them and diseases, as well as
      negation and speculation, that can change the meaning of the language. The deep
      learning models designed for identifying disabilities and their relationships to
      diseases in new documents show that the corpus allows obtaining an F-measure of
      around 81% for the disability recognition and 75% for relation extraction.

PMID- 30195421
TI  - Mammographic mass segmentation using fuzzy contours.
AB  - BACKGROUND AND OBJECTIVE: Accurate mass segmentation in mammographic images is a
      critical requirement for computer-aided diagnosis systems since it allows
      accurate feature extraction and thus improves classification precision. METHODS:
      In this paper, a novel automatic breast mass segmentation approach is presented.
      This approach consists of mainly three stages: contour initialization applied to
      a given region of interest; construction of fuzzy contours and estimation of
      fuzzy membership maps of different classes in the considered image; integration
      of these maps in the Chan-Vese model to get a fuzzy-energy based model that is
      used for final delineation of mass. RESULTS: The proposed approach is evaluated
      using mass regions of interest extracted from the mini-MIAS database. The
      experimental results show that the proposed method achieves an average true
      positive rate of 91.12% with a precision of 88.08%. CONCLUSIONS: The achieved
      results show high accuracy in breast mass segmentation when compared to manually
      annotated ground truth and to other methods from the literature.

PMID- 30195422
TI  - Analysis of PCG signals using quality assessment and homomorphic filters for
      localization and classification of heart sounds.
AB  - BACKGROUND AND OBJECTIVE: Accurate localization of heart beats in phonocardiogram
      (PCG) signal is very crucial for correct segmentation and classification of heart
      sounds into S1 and S2. This task becomes challenging due to inclusion of noise in
      acquisition process owing to number of different factors. In this paper we
      propose a system for heart sound localization and classification into S1 and S2.
      The proposed system introduces the concept of quality assessment before
      localization, feature extraction and classification of heart sounds. METHODS: The
      signal quality is assessed by predefined criteria based upon number of peaks and
      zero crossing of PCG signal. Once quality assessment is performed, then heart
      beats within PCG signal are localized, which is done by envelope extraction using
      homomorphic envelogram and finding prominent peaks. In order to classify
      localized peaks into S1 and S2, temporal and time-frequency based statistical
      features have been used. Support Vector Machine using radial basis function
      kernel is used for classification of heart beats into S1 and S2 based upon
      extracted features. The performance of the proposed system is evaluated using
      Accuracy, Sensitivity, Specificity, F-measure and Total Error. The dataset
      provided by PASCAL classifying heart sound challenge is used for testing.
      RESULTS: Performance of system is significantly improved by quality assessment.
      Results shows that proposed Localization algorithm achieves accuracy up to 97%
      and generates smallest total average error among top 3 challenge participants.
      The classification algorithm achieves accuracy up to 91%. CONCLUSION: The system
      provides firm foundation for the detection of normal and abnormal heart sounds
      for cardiovascular disease detection.

PMID- 30195423
TI  - A review of image analysis and machine learning techniques for automated cervical
      cancer screening from pap-smear images.
AB  - BACKGROUND AND OBJECTIVE: Early diagnosis and classification of a cancer type can
      help facilitate the subsequent clinical management of the patient. Cervical
      cancer ranks as the fourth most prevalent cancer affecting women worldwide and
      its early detection provides the opportunity to help save life. To that end,
      automated diagnosis and classification of cervical cancer from pap-smear images
      has become a necessity as it enables accurate, reliable and timely analysis of
      the condition's progress. This paper presents an overview of the state of the art
      as articulated in prominent recent publications focusing on automated detection
      of cervical cancer from pap-smear images. METHODS: The survey reviews
      publications on applications of image analysis and machine learning in automated
      diagnosis and classification of cervical cancer from pap-smear images spanning 15
      years. The survey reviews 30 journal papers obtained electronically through four
      scientific databases (Google Scholar, Scopus, IEEE and Science Direct) searched
      using three sets of keywords: (1) segmentation, classification, cervical cancer;
      (2) medical imaging, machine learning, pap-smear; (3) automated system,
      classification, pap-smear. RESULTS: Most of the existing algorithms facilitate an
      accuracy of nearly 93.78% on an open pap-smear data set, segmented using CHAMP
      digital image software. K-nearest-neighbors and support vector machines
      algorithms have been reported to be excellent classifiers for cervical images
      with accuracies of over 99.27% and 98.5% respectively when applied to a 2-class
      classification problem (normal or abnormal). CONCLUSION: The reviewed papers
      indicate that there are still weaknesses in the available techniques that result
      in low accuracy of classification in some classes of cells. Moreover, most of the
      existing algorithms work either on single or on multiple cervical smear images.
      This accuracy can be increased by varying various parameters such as the features
      to be extracted, improvement in noise removal, using hybrid segmentation and
      classification techniques such of multi-level classifiers. Combining K-nearest
      neighbors algorithm with other algorithm(s) such as support vector machines,
      pixel level classifications and including statistical shape models can also
      improve performance. Further, most of the developed classifiers are tested on
      accurately segmented images using commercially available software such as CHAMP
      software. There is thus a deficit of evidence that these algorithms will work in
      clinical settings found in developing countries (where 85% of cervical cancer
      incidences occur) that lack sufficient trained cytologists and the funds to buy
      the commercial segmentation software.

PMID- 30195424
TI  - A topological approach to delineation and arrhythmic beats detection in
      unprocessed long-term ECG signals.
AB  - BACKGROUND AND OBJECTIVE: Arrhythmias are one of the most common symptoms of
      cardiac failure. They are usually diagnosed using ECG recordings, particularly
      long ambulatory recordings (AECG). These recordings are tedious to interpret by
      humans due to their extent (up to 48 h) and the relative scarcity of arrhythmia
      events. This makes automated systems for detecting various AECG anomalies
      indispensable. In this work we present a novel procedure based on topological
      principles (Morse theory) for detecting arrhythmic beats in AECG. It works in
      nearly real-time (delayed by a 14 s window), and can be applied to raw
      (unprocessed) ECG signals. METHODS: The procedure is based on a subject-specific
      adaptation of the one-dimensional discrete Morse theory (ADMT), which represents
      the signal as a sequence of its most important extrema. The ADMT algorithm is
      applied twice; for low-amplitude, high-frequency noise removal, and for detection
      of the characteristic waves of individual ECG beats. The waves are annotated
      using the ADMT algorithm and template matching. The annotated beats are then
      compared to the adjacent beats with two measures of similarity: the distance
      between two beats, and the difference in shape between them. The two measures of
      similarity are used as inputs to a decision tree algorithm that classifies the
      beats as normal or abnormal. The classification performance is evaluated with the
      leave-one-record-out cross-validation method. RESULTS: Our approach was tested on
      the MIT-BIH database, where it exhibited a classification accuracy of 92.73%, a
      sensitivity of 73.35%, a specificity of 96.70%, a positive predictive value of
      88.01%, and a negative predictive value of 95.73%. CONCLUSIONS: Compared to
      related studies, our algorithm requires less preprocessing while retaining the
      capability to detect and classify beats in almost real-time. The algorithm
      exhibits a high degree of accuracy in beats detection and classification that are
      at least comparable to state-of-the-art methods.

PMID- 30195425
TI  - Attentional bias in MDD: ERP components analysis and classification using a dot
      probe task.
AB  - BACKGROUND AND OBJECTIVE: Strands of evidence have supported existence of
      negative attentional bias in patients with depression. This study aimed to assess
      the behavioral and electrophysiological signatures of attentional bias in major
      depressive disorder (MDD) and explore whether ERP components contain valuable
      information for discriminating between MDD patients and healthy controls (HCs).
      METHODS: Electroencephalography data were collected from 17 patients with MDD and
      17 HCs in a dot-probe task, with emotional-neutral pairs as experimental
      materials. Fourteen features related to ERP waveform shape were generated. Then,
      Correlated Feature Selection (CFS), ReliefF and GainRatio (GR) were applied for
      feature selection. For discriminating between MDDs and HCs, k-nearest neighbor
      (KNN), C4.5, Sequential Minimal Optimization (SMO) and Logistic Regression (LR)
      were used. RESULTS: Behaviorally, MDD patients showed significantly shorter
      reaction time (RT) to valid than invalid sad trials, with significantly higher
      bias score for sad-neutral pairs. Analysis of split-half reliability in RT
      indices indicated a strong reliability in RT, while coefficients of RT bias
      scores neared zero. These behavioral effects were supported by ERP results. MDD
      patients had higher P300 amplitude with the probe replacing a sad face than a
      neutral face, indicating difficult attention disengagement from negative
      emotional faces. Meanwhile, data mining analysis based on ERP components
      suggested that CFS was the best feature selection algorithm. Especially for the
      P300 induced by valid sad trials, the classification accuracy of CFS combination
      with any classifier was above 85%, and the KNN (k = 3) classifier achieved the
      highest accuracy (94%). CONCLUSIONS: MDD patients show difficulty in attention
      disengagement from negative stimuli, reflected by P300. The CFS over other
      methods leads to a good overall performance in most cases, especially when KNN
      classifier is used for P300 component classification, illustrating that ERP
      component may be applied as a tool for auxiliary diagnosis of depression.

PMID- 30195426
TI  - Complex-valued unsupervised convolutional neural networks for sleep stage
      classification.
AB  - BACKGROUND AND OBJECTIVE: Despite numerous deep learning methods being developed
      for automatic sleep stage classification, almost all the models need labeled
      data. However, obtaining labeled data is a subjective process. Therefore, the
      labels will be different between two experts. At the same time, obtaining labeled
      data also is a time-consuming task. Even an experienced expert requires hours to
      annotate the sleep stage patterns. More important, as the development of wearable
      sleep devices, it is very difficult to obtain labeled sleep data. Therefore,
      unsupervised training algorithm is very important for sleep stage classification.
      Hence, a new sleep stage classification method named complex-valued unsupervised
      convolutional neural networks (CUCNN) is proposed in this study. METHODS: The
      CUCNN operates with complex-valued inputs, outputs, and weights, and its training
      strategy is greedy layer-wise training. It is composed of three phases: phase
      encoder, unsupervised training and complex-valued classification. Phase encoder
      is used to translate real-valued inputs into complex numbers. In the unsupervised
      training phase, the complex-valued K-means is used to learn filters which will be
      used in the convolution. RESULTS: The classification performances of handcrafted
      features are compared with those of learned features via CUCNN. The total
      accuracy (TAC) and kappa coefficient of the sleep stage from UCD dataset are 87%
      and 0.8, respectively. Moreover, the comparison experiments indicate that the
      TACs of the CUCNN from UCD and MIT-BIH datasets outperform these of unsupervised
      convolutional neural networks (UCNN) by 12.9% and 13%, respectively.
      Additionally, the convergence of CUCNN is much faster than that of UCNN in most
      cases. CONCLUSIONS: The proposed method is fully automated and can learn features
      in an unsupervised fashion. Results show that unsupervised training and automatic
      feature extraction on sleep data are possible, which are very important for home
      sleep monitoring.

PMID- 30195427
TI  - A lightweight rapid application development framework for biomedical image
      analysis.
AB  - Biomedical imaging analysis typically comprises a variety of complex tasks
      requiring sophisticated algorithms and visualising high dimensional data. The
      successful integration and deployment of the enabling software to clinical
      (research) partners, for rigorous evaluation and testing, is a crucial step to
      facilitate adoption of research innovations within medical settings. In this
      paper, we introduce the Simple Medical Imaging Library Interface (SMILI), an
      object oriented open-source framework with a compact suite of objects geared for
      rapid biomedical imaging (cross-platform) application development and deployment.
      SMILI supports the development of both command-line (shell and Python scripting)
      and graphical applications utilising the same set of processing algorithms. It
      provides a substantial subset of features when compared to more complex packages,
      yet it is small enough to ship with clinical applications with limited overhead
      and has a license suitable for commercial use. After describing where SMILI fits
      within the existing biomedical imaging software ecosystem, by comparing it to
      other state-of-the-art offerings, we demonstrate its capabilities in creating a
      clinical application for manual measurement of cam-type lesions of the femoral
      head-neck region for the investigation of femoro-acetabular impingement (FAI)
      from three dimensional (3D) magnetic resonance (MR) images of the hip. This
      application for the investigation of FAI proved to be convenient for radiological
      analyses and resulted in high intra (ICC=0.97) and inter-observer (ICC=0.95)
      reliabilities for measurement of alpha-angles of the femoral head-neck region. We
      believe that SMILI is particularly well suited for prototyping biomedical imaging
      applications requiring user interaction and/or visualisation of 3D mesh, scalar,
      vector or tensor data.

PMID- 30195428
TI  - Measuring the Impact of Nonignorable Missingness Using the R Package isni.
AB  - BACKGROUND AND OBJECTIVE: The popular assumption of ignorability simplifies
      analyses with incomplete data, but if it is not satisfied, results may be
      incorrect. Therefore it is necessary to assess the sensitivity of empirical
      findings to this assumption. We have created a user-friendly and freely available
      software program to conduct such analyses. METHOD: One can evaluate the
      dependence of inferences on the assumption of ignorability by measuring their
      sensitivity to its violation. One tool for such an analysis is the index of local
      sensitivity to nonignorability (ISNI), which evaluates the rate of change of
      parameter estimates to the assumed degree of nonignorability in the neighborhood
      of an ignorable model. Computation of ISNI avoids the need to estimate a
      nonignorable model or to posit a specific magnitude of nonignorability. Our new R
      package, named isni, implements ISNI analysis for some common data structures and
      corresponding statistical models. RESULT: The isni package computes ISNI in the
      generalized linear model for independent data, and in the marginal multivariate
      Gaussian model and the linear mixed model for longitudinal/clustered data. It
      allows for arbitrary patterns of missingness caused by dropout and/or
      intermittent missingness. Examples illustrate its use and features. CONCLUSIONS:
      The R package isni enables a systematic and efficient sensitivity analysis that
      informs evaluations of reliability and validity of empirical findings from
      incomplete data.

PMID- 30195429
TI  - Availability and use of in-patient electronic health records in low resource
      setting.

PMID- 30195430
TI  - Non-invasive assessment of liver quality in transplantation based on thermal
      imaging analysis.
AB  - BACKGROUND AND OBJECTIVE: Liver quality evaluation is one of the vital steps for
      predicting the success of liver transplantation. Current evaluation methods, such
      as biopsy and visual inspection, which are either invasive or lack of consistent
      standards, provide limited predictive value of long-term transplant viability.
      Objective analytical models, based on the real-time infrared images of livers
      during perfusion and preservation, are proposed as novel methods to precisely
      evaluate donated liver quality. METHODS: In this study, by using principal
      component analysis to extract infrared image features as predictors, we construct
      a multivariate logistic regression model for single liver quality evaluation, and
      a multi-task learning logistic regression model for cross-liver quality
      evaluation. RESULTS: The single liver quality predictions show testing errors of
      0%. The leave-one-liver-out predictions show testing errors ranging from 9% to
      36%. CONCLUSIONS: It is found that there is a strong correlation between the
      viability of livers and the infrared image features in both single liver and
      cross-liver quality evaluations. These analytical methods also determine that the
      selected significant infrared image features indicate regional difference in
      viability and show that more stringent pre-implantation evaluation may be needed
      to predict transplant outcomes.

PMID- 30195431
TI  - Predictive models for hospital readmission risk: A systematic review of methods.
AB  - OBJECTIVES: Hospital readmission risk prediction facilitates the identification
      of patients potentially at high risk so that resources can be used more
      efficiently in terms of cost-benefit. In this context, several models for
      readmission risk prediction have been proposed in recent years. The goal of this
      review is to give an overview of prediction models for hospital readmission,
      describe the data analysis methods and algorithms used for building the models,
      and synthesize their results. METHODS: Studies that reported the predictive
      performance of a model for hospital readmission risk were included. We defined
      the scope of the review and accordingly built a search query to select the
      candidate papers. This query string was used as input for the chosen search
      engines, namely PubMed and Google Scholar. For each study, we recorded the
      population, feature selection method, classification algorithm, sample size,
      readmission threshold, readmission rate and predictive performance of the model.
      RESULTS: We identified 77 studies that met the inclusion criteria, out of 265
      citations. In 68% of the studies (n = 52) logistic regression or other regression
      techniques were utilized as the main method. Ten (13%) studies used survival
      analysis for model construction, while 14 (18%) used machine learning techniques
      for classification, of which decision tree-based methods and SVM were the most
      utilized algorithms. Among these, only four studies reported the use of any class
      imbalance addressing technique, of which resampling is the most frequent (75%).
      The performance of the models varied significantly among studies, with Area Under
      the ROC Curve (AUC) values in the ranges between 0.54 and 0.92. CONCLUSION:
      Logistic regression and survival analysis have been traditionally the most widely
      used techniques for model building. Nevertheless, machine learning techniques are
      becoming increasingly popular in recent years. Recent comparative studies suggest
      that machine learning techniques can improve prediction ability over traditional
      statistical approaches. Regardless, the lack of an appropriate benchmark dataset
      of hospital readmissions makes a comparison of models' performance across
      different studies difficult.

PMID- 30195432
TI  - Hybrid L1/2  + 2 method for gene selection in the Cox proportional hazards model.
AB  - BACKGROUND AND OBJECTIVE: An important issue in genomic research is to identify
      the significant genes that related to survival from tens of thousands of genes.
      Although Cox proportional hazards model is a conventional survival analysis
      method, it does not induce the gene selection. METHODS: In this paper, we extend
      the hybrid L1/2  + 2 regularization (HLR) idea to the censored survival
      situation, a new edition of sparse Cox model based on the HLR method has been
      proposed. We develop two algorithms for solving the HLR penalized Cox model; one
      is the coordinate descent algorithm with HLR thresholding operator, the other is
      the weight iteration method. RESULTS: The proposed method was tested on six
      public mRNA data sets of serval kinds of cancers, AML, Breast cancer, Pancreatic
      cancer, DLBCL and Melanoma. The test results indicate that the method identified
      a small subset of genes but essential while giving best or equivalent predictive
      performance, as compared to some popular methods. CONCLUSIONS: The results of
      empirical and simulations imply that the proposed strategy is highly competitive
      in studying high dimensional survival data among several state-of-the-art
      methods.

PMID- 30195433
TI  - Evaluating the outcomes of medical informatics development as a discipline in
      China: A publication perspective.
AB  - BACKGROUND: As the world's second largest economy, China makes unique
      contributions to the world in many fields, including sociology, the economy,
      technology and defense. Medical informatics (MI) is an important cross
      disciplinary field that, along with its applications, has received massive
      funding from the Chinese government. However, the question of how to evaluate
      China's input and output in MI remains important and complex issue of great
      significance for China and the rest of the world. OBJECTIVE: This paper analyzed,
      for the first time, the quality and quantity of research by Chinese academics in
      MI based on their articles published in international specialty journals in
      recent years and examined MI research hotspots in China. Our purpose is to
      summarize the experiences and lessons learned by China and the rest of the world
      as they develop MI. METHOD: We targeted 18 MI journals listed in the JCR 2016
      report and searched for papers published by Chinese academics in these 18
      journals in the WOS and PUBMED databases and on journal sites. We also performed
      data cleansing and categorized the obtained information. We used Excel, SPSS,
      Ucinet and NetDraw to conduct quantitative analyses on the research papers.
      RESULTS: A total of 1340 articles satisfied the inclusion criteria of this study.
      We observed a significant upward trend in the number of articles published over
      time, particularly after 2011. Lei Jianbo, Huang Zhengxing and Li Jin-song are
      active Chinese authors in the MI discipline who have written many high-quality
      publications. Meanwhile, universities remain the primary breeding grounds for
      scientific research: 93.36% of the articles came from universities. Zhejiang
      University published the most first-author articles, whereas Zhejiang University,
      Shanghai Jiao Tong University and Tsinghua University produced 17.76% of the
      total articles. According to the lists of authors, 24% of the papers were co
      authored with foreign researchers. This rate of cooperation is increasing each
      year, from 5.88% to the current rate of 39.04%. An analysis of keywords showed
      that "EMR", "SVM", "Authentication", "Telecare medical information system",
      "EEG", "ECG" and "RFID" were the most frequently searched terms in popular
      technological fields, including artificial intelligence and image processing. In
      recent years, there has been a significant increase in the number of high
      frequency keywords and a broadening range of research fields, which has led to
      the emergence of several research hotspots, including MI systems, mobile health
      care, telecare, data mining and machine learning. CONCLUSIONS: Through the
      quantitative analysis of publications, we discovered the emergence of three
      stages - infancy, slow growth and rapid growth - in China's MI research in recent
      years as academics make achievements in their research works. The global
      influence of Chinese academics is growing, and they are making increasingly
      conscious efforts to enter into research collaborations with foreign researchers.
      The findings of Chinese academics' publications are gaining international
      recognition.

PMID- 30195434
TI  - Adrenal tumor segmentation method for MR images.
AB  - BACKGROUND AND OBJECTIVE: Adrenal tumors, which occur on adrenal glands, are
      incidentally determined. The liver, spleen, spinal cord, and kidney surround the
      adrenal glands. Therefore, tumors on the adrenal glands can be adherent to other
      organs. This is a problem in adrenal tumor segmentation. In addition, low
      contrast, non-standardized shape and size, homogeneity, and heterogeneity of the
      tumors are considered as problems in segmentation. METHODS: This study proposes a
      computer-aided diagnosis (CAD) system to segment adrenal tumors by eliminating
      the above problems. The proposed hybrid method incorporates many image processing
      methods, which include active contour, adaptive thresholding, contrast limited
      adaptive histogram equalization (CLAHE), image erosion, and region growing.
      RESULTS: The performance of the proposed method was assessed on 113 Magnetic
      Resonance (MR) images using seven metrics: sensitivity, specificity, accuracy,
      precision, Dice Coefficient, Jaccard Rate, and structural similarity index
      (SSIM). The proposed method eliminates some of the discussed problems with
      success rates of 74.84%, 99.99%, 99.84%, 93.49%, 82.09%, 71.24%, 99.48% for the
      metrics, respectively. CONCLUSIONS: This study presents a new method for adrenal
      tumor segmentation, and avoids some of the problems preventing accurate
      segmentation, especially for cyst-based tumors.

PMID- 30195435
TI  - AI in Medicine: Big Data Remains a Challenge.

PMID- 30195438
TI  - Aligning Single-Cell Developmental and Reprogramming Trajectories Identifies
      Molecular Determinants of Myogenic Reprogramming Outcome.
AB  - Cellular reprogramming through manipulation of defined factors holds great
      promise for large-scale production of cell types needed for use in therapy and
      for revealing principles of gene regulation. However, most reprogramming systems
      are inefficient, converting only a fraction of cells to the desired state. Here,
      we analyze MYOD-mediated reprogramming of human fibroblasts to myotubes, a well
      characterized model system for direct conversion by defined factors, at
      pseudotemporal resolution using single-cell RNA-seq. To expose barriers to
      efficient conversion, we introduce a novel analytic technique, trajectory
      alignment, which enables quantitative comparison of gene expression kinetics
      across two biological processes. Reprogrammed cells navigate a trajectory with
      branch points that correspond to two alternative decision points, with cells that
      select incorrect branches terminating at aberrant or incomplete reprogramming
      outcomes. Analysis of these branch points revealed insulin and BMP signaling as
      crucial molecular determinants of reprogramming. Single-cell trajectory alignment
      enables rigorous quantitative comparisons between biological trajectories found
      in diverse processes in development, reprogramming, and other contexts.

PMID- 30195436
TI  - Machine Learning Predicts the Yeast Metabolome from the Quantitative Proteome of
      Kinase Knockouts.
AB  - A challenge in solving the genotype-to-phenotype relationship is to predict a
      cell's metabolome, believed to correlate poorly with gene expression. Using
      comparative quantitative proteomics, we found that differential protein
      expression in 97 Saccharomyces cerevisiae kinase deletion strains is non
      redundant and dominated by abundance changes in metabolic enzymes. Associating
      differential enzyme expression landscapes to corresponding metabolomes using
      network models provided reasoning for poor proteome-metabolome correlations;
      differential protein expression redistributes flux control between many enzymes
      acting in concert, a mechanism not captured by one-to-one correlation statistics.
      Mapping these regulatory patterns using machine learning enabled the prediction
      of metabolite concentrations, as well as identification of candidate genes
      important for the regulation of metabolism. Overall, our study reveals that a
      large part of metabolism regulation is explained through coordinated enzyme
      expression changes. Our quantitative data indicate that this mechanism explains
      more than half of metabolism regulation and underlies the interdependency between
      enzyme levels and metabolism, which renders the metabolome a predictable
      phenotype.

PMID- 30195439
TI  - Effects of inflammatory cytokines IFN-gamma, TNF-alpha and IL-6 on the viability
      and functionality of human pluripotent stem cell-derived neural cells.
AB  - Multiple Sclerosis (MS) is an inflammatory neurodegenerative disease, where
      neural progenitor cell (NPC) transplantation has been suggested as a potential
      neuroprotective therapeutic strategy. Since the effect of inflammation on NPCs is
      poorly known, their effect on the survival and functionality of human NPCs were
      studied. Treatment with interleukin (IL)-6, tumor necrosis factor (TNF)-alpha and
      interferon (IFN)-gamma did not induced cytotoxicity, but IFN-gamma treatment
      showed decreased proliferation and neuronal migration. By contrast, increased
      proliferation and inhibition of electrical activity were detected after TNF-alpha
      treatment. Treatments induced secretion of inflammatory factors. Inflammatory
      cytokines appear to modulate proliferation as well as the cellular and functional
      properties of human NPCs.

PMID- 30195440
TI  - Remunerated patient care services and injections by pharmacists: An international
      update.
AB  - OBJECTIVES: Recognizing pharmacists' increasing roles as primary care providers,
      programs offering remuneration for patient care services, and the administration
      of injections by pharmacists continue to be implemented. The objective of this
      article is to provide an update on remuneration programs available to pharmacists
      internationally for nondispensing services. DATA SOURCES: Systematic searches for
      relevant articles published from January 2013 to February 2018 across Pubmed
      (Medline), Embase, International Pharmaceutical Abstracts, Cochrane Library,
      Econlit, Scopus, and Web of Science. Gray literature searches, including targeted
      searches of websites of payers and pharmacy associations, were also performed.
      STUDY SELECTION: Programs were included if they were newly introduced or had
      changes to patient eligibility criteria and fees since previously published
      reviews and if they were established programs offered by third-party payers for
      activities separate from dispensing. DATA EXTRACTION: Descriptive information on
      each program was extracted, including the program's jurisdiction (country and
      state, provincial, or regional level, as applicable), payer, service description,
      patient eligibility criteria, and fee structure. RESULTS: Over the 5-year period
      studied, 95 new programs for noninjection patient care services and 37 programs
      for pharmacist-administered injections were introduced. Large ranges in fees
      offered for similar programs were observed across programs, even within the same
      country or region, at an average of $US 71 for an initial medication review, $19
      for follow-ups to these reviews, $18 for prescription adaptations, and $13 for
      injection administration. Apart from some smoking cessation programs in England,
      which offered incentive payments for successful quits, all services were
      remunerated on a fee-for-service basis, often in the form of a flat fee
      regardless of the time spent providing the service. CONCLUSION: Although funding
      for pharmacists' activities continues to show growth, concerns identified in
      previous reviews persist, including the great variability in remunerated
      activities, patient eligibility, and fees. These issues may limit opportunities
      for multijurisdictional program and service outcome evaluation.

PMID- 30195437
TI  - Inferring Metabolic Mechanisms of Interaction within a Defined Gut Microbiota.
AB  - The diversity and number of species present within microbial communities create
      the potential for a multitude of interspecies metabolic interactions. Here, we
      develop, apply, and experimentally test a framework for inferring metabolic
      mechanisms associated with interspecies interactions. We perform pairwise growth
      and metabolome profiling of co-cultures of strains from a model mouse microbiota.
      We then apply our framework to dissect emergent metabolic behaviors that occur in
      co-culture. Based on one of the inferences from this framework, we identify and
      interrogate an amino acid cross-feeding interaction and validate that the
      proposed interaction leads to a growth benefit in vitro. Our results reveal the
      type and extent of emergent metabolic behavior in microbial communities composed
      of gut microbes. We focus on growth-modulating interactions, but the framework
      can be applied to interspecies interactions that modulate any phenotype of
      interest within microbial communities.

PMID- 30195441
TI  - Multi affected pedigree with congenital microcephaly: WES revealed PNKP gene
      mutation.
AB  - Microcephaly is a rare neurological disorder, occurs in both isolated and
      syndromic forms. This classification could be confusing in rare disorders with
      variable phenotypic characteristics. However, identification of the causative
      gene through genetic study would allow determining the definite diagnosis. Here
      we reported a novel missense variant c.1133A>C (p.Lys378Thr) on the 13th exon of
      PNKP gene identified by whole exome sequencing (WES) in an Iranian multi-affected
      family with microcephaly, seizures and developmental delay (MCSZ) disorder. Data
      analysis suggested this variant as a pathogenic mutation which is co-segregate
      with the disease in the pedigree. PNKP gene mutation is consistent with the
      clinical features of the affected family members. Regarding both genetic findings
      and clinical examinations, the reported pedigree can be considered as another
      affected family with MCSZ syndrome, which has been reported about 10 cases
      worldwide. This study proves the application of WES for determining the final
      diagnosis in complicated neurodevelopmental disorders.

PMID- 30195442
TI  - Corrigendum to "Dating the Middle Palaeolithic deposits of La Quina Amont
      (Charente, France) using luminescence methods" [Journal of Human Evolution 109
      (2017) 30-45].

PMID- 30195443
TI  - In vitro antileishmanial effects of Physalis angulata root extract on Leishmania
      infantum.
AB  - OBJECTIVE: In the present study, we evaluated the effects of the aqueous extract
      of Physalis angulata root (AEPa) on Leishmania infantum proliferation,
      morphology, and the driving mechanism in leishmanicidal activity and modulatory
      action on macrophages. METHODS: L. infantum promastigotes were treated with 50
      and 100 ug/mL AEPa for 72 h and then antipromastigote assay was performed by
      counts in a Newbauer chamber, morphological changes were analyzed by transmission
      electron microscopy and the mechanism of the leishmanicidal activity was
      detected. In addition, macrophages were infected with L. infantum and were used
      to evaluate anti-amastigote activity of AEPa and effects of AEPa on cytokine
      secretion after 72-hour treatment. RESULTS: Treatment with AEPa reduced the
      numbers of L. infantum promastigotes (50% inhibitory concentration (IC50) = 65.9
      MUg/mL; selectivity index (SI) = 22.1) and amastigotes (IC50 = 37.9 MUg/mL; SI =
      38.5) compared with the untreated control. Amphotericin B reduced 100% of the
      promastigote numbers after 72 h of treatment (IC50 = 0.2 MUg/mL). AEPa induced
      several morphological changes and increased the production of reactive oxygen
      species and apoptotic death in promastigotes after treating for 72 h. AEPa (100
      MUg/mL) promoted tumor necrosis factor-alpha secretion in macrophages infected
      with L. infantum after 72 h of treatment, but did not induce an increase in this
      cytokine in noninfected macrophages. In addition, AEPa showed no cytotoxic effect
      on J774-A1 cells (50% cytotoxic concentration >1000 MUg/mL). CONCLUSION: AEPa
      presented antileishmanial activity against the promastigotes and amastigotes of
      L. infantum without macrophage cytotoxicity; these results show that natural
      products such as P. angulata have leishmanicidal potential and in the future may
      be an alternative treatment for leishmaniasis.

PMID- 30195444
TI  - A health systems approach to identifying barriers to breast cancer screening
      programmes. Methodology and application in six European countries.
AB  - The benefits of population-based screening for breast cancer are now accepted
      although, in practice, programmes often fail to achieve their full potential. In
      this paper, we propose a conceptual model that situates screening programmes
      within the broader health system to understand the factors that influence their
      outcomes. We view the overall screening system as having multiple sub-systems to
      identify the population at risk, generate knowledge of effectiveness, maximise
      uptake, operate the programme, and optimise follow-up and assurance of subsequent
      treatment. Based on this model we have developed the Barriers to Effective
      Screening Tool (BEST) for analysing government-led, population-based screening
      programmes from a health systems perspective. Conceived as a self-assessment
      tool, we piloted the tool with key informants in six European countries (Estonia,
      Finland, Hungary, Italy, The Netherlands and Slovenia) to identify barriers to
      the optimal operation of population-based breast cancer screening programmes. The
      pilot provided valuable feedback on the barriers affecting breast cancer
      screening programmes and stimulated a greater recognition among those operating
      them of the need to take a health systems perspective. In addition, the pilot led
      to further development of the tool and provided a foundation for further research
      into how to overcome the identified barriers.

PMID- 30195445
TI  - Association between obesity and mortality in adult patients receiving invasive
      mechanical ventilation: A systematic review and meta-analysis.
AB  - OBJECTIVE: To evaluate if there is an association between obesity and mortality
      in the Intensive Care Unit (ICU) in adult patients receiving invasive mechanical
      ventilation. DESIGN: Systematic review with meta-analysis. SCOPE: ICU. DATA
      SOURCE: A search was made in MEDLINE, Cochrane Library, CINAHL and Global Health
      databases without language restriction, until February 21, 2017. SELECTION OF
      STUDIES: Studies that reported mortality in the ICU in obese versus non-obese
      patients who received IMV were included. MAIN VARIABLES: Mortality in the ICU.
      RESULTS: 2163 articles were found, of which 14 studies were included. No
      statistically significant differences were found between obese and non-obese
      patients with respect to the variable mortality in the ICU (OR: 0.94, 95% CI:
      0.81-1.10, P=.45). CONCLUSION: No relationship was found between the subgroup of
      obese adult patients receiving IMV and the mortality variable in the ICU.

PMID- 30195446
TI  - Generalized phase compensator of continuous time plants.
AB  - This work proposes a novel design method for generalized order lead/lag
      compensators. With respect to the traditional lead/lag compensator, it introduces
      a new parameter, beta, which is a non-integer number. A new design method of the
      compensator is introduced in order to quantify its design parameters. Compared to
      its integer order counterpart, the generalized order lead compensator facilitates
      with the unique solution of desired design specifications with maximum phase at
      the desired gain cross-over frequency to achieve reshaping of the loop frequency
      domain characteristics. On the other hand, generalized order lag compensator is
      designed so as to allow minimum phase lag at the new gain crossover frequency.
      Examples with simulation and real-time results are presented to validate the
      efficacy of the proposed approach.

PMID- 30195448
TI  - Loss of Tight Junction Protein Claudin 18 Promotes Progressive Neoplasia
      Development in Mouse Stomach.
AB  - BACKGROUND & AIMS: Loss of claudin 18 (CLDN18), a membrane-spanning tight
      junction protein, occurs during early stages of development of gastric cancer and
      associates with shorter survival times of patients. We investigated whether loss
      of CLDN18 occurs in mice that develop intraepithelial neoplasia with invasive
      glands due to infection with Helicobacter pylori, and whether loss is sufficient
      to promote the development of similar lesions in mice with or without H pylori
      infection. METHODS: We performed immunohistochemical analyses in levels of CLDN18
      in archived tissues from B6:129 mice infected with H pylori for 6 to 15 months.
      We analyzed gastric tissues from B6:129S5-Cldn18tm1Lex/Mmucd mice, in which the
      CLDN18 gene was disrupted in gastric tissues (CLDN18-knockout mice), or from
      control mice with a full-length CLDN18 gene (CLDN18+/+; B6:129S5/SvEvBrd) or
      heterozygous disruption of CLDN18 (CLDN18+/-; B6:129S5/SvEvBrd) that were
      infected with H pylori SS1 or PMSS1 at 6 weeks of age and tissues collected for
      analysis at 20 and 30 weeks after infection. Tissues from CLDN18-knockout mice
      and control mice with full-length CLDN18 gene expression were also analyzed
      without infection at 7 weeks and 2 years after birth. Tissues from control and
      CLDN18-knockout mice were analyzed by electron microscopy, stained by
      conventional methods and analyzed for histopathology, prepared by laser capture
      microdissection and analyzed by RNAseq, and immunostained for lineage markers,
      proliferation markers, and stem cell markers and analyzed by super-resolution or
      conventional confocal microscopy. RESULTS: CLDN18 had a basolateral rather than
      apical tight junction localization in gastric epithelial cells. B6:129 mice
      infected with H pylori, which developed intraepithelial neoplasia with invasive
      glands, had increasing levels of CLDN18 loss over time compared with uninfected
      mice. In B6:129 mice infected with H pylori compared with uninfected mice, CLDN18
      was first lost from most gastric glands followed by disrupted and reduced
      expression in the gastric neck and in surface cells. Gastric tissues from CLDN18
      knockout mice had low levels of inflammation but increased cell proliferation,
      expressed markers of intestinalized proliferative spasmolytic polypeptide
      expressing metaplasia, and had defects in signal transduction pathways including
      p53 and STAT signaling by 7 weeks after birth compared with full-length CLDN18
      gene control mice. By 20 to 30 weeks after birth, gastric tissues from uninfected
      CLDN18-knockout mice developed intraepithelial neoplasia that invaded the
      submucosa; by 2 years, gastric tissues contained large and focally dysplastic
      polypoid tumors with invasive glands that invaded the serosa. CONCLUSIONS: H
      pylori infection of B6:129 mice reduced the expression of CLDN18 early in gastric
      cancer progression, similar to previous observations from human gastric tissues.
      CLDN18 regulates cell lineage differentiation and cellular signaling in mouse
      stomach; CLDN18-knockout mice develop intraepithelial neoplasia and then large
      and focally dysplastic polypoid tumors in the absence of H pylori infection.

PMID- 30195449
TI  - Evolving Considerations for Thiopurine Therapy for Inflammatory Bowel Diseases-A
      Clinical Practice Update: Commentary.
AB  - Thiopurines (azathioprine, mercaptopurine, thioguanine) and methotrexate are
      widely used in a variety of clinical management scenarios for ulcerative colitis
      and Crohn's disease. With the introduction of biologic therapies over the last 2
      decades, controversies have emerged as to how these immunomodulators should be
      used in clinical practice, either alone as monotherapies or in combination with
      biologic therapies. Here, we provide a summary of evidence and our
      interpretations regarding how physicians can or should incorporate these agents
      into clinical practice. We have organized the review into sections regarding
      their utility as monotherapy or as combination therapy with biologics and safety
      considerations. Clinical pharmacologic considerations are important regarding
      both efficacy and safety.

PMID- 30195450
TI  - "Doc, I Can't Walk"-A Classic Presentation of a Rare Disease.

PMID- 30195447
TI  - Efficacy and Safety of Budesonide, vs Mesalazine or Placebo, as Induction Therapy
      for Lymphocytic Colitis.
AB  - BACKGROUND & AIMS: Lymphocytic colitis is a common cause of chronic, nonbloody
      diarrhea. However, the effects of treatment are unclear and randomized placebo
      controlled trials were requested in a Cochrane review. We performed a randomized,
      placebo-controlled, multicenter study to evaluate budesonide and mesalazine as
      induction therapy for lymphocytic colitis. METHODS: Patients with active
      lymphocytic colitis were randomly assigned to groups given budesonide 9 mg once
      daily (Budenofalk granules), mesalazine 3 g once daily (Salofalk granules), or
      placebo for 8 weeks in a double-blind, double-dummy design. The primary endpoint
      was clinical remission, defined as <=21 stools (including <=6 watery stools), in
      the 7 days before week 8. RESULTS: The final analysis included 57 patients (19
      per group). Most patients were female (72%) and the mean age was 59 years. The
      proportion of patients in clinical remission at week 8 was significantly higher
      in the budesonide group than in the placebo group (intention-to-treat analysis,
      79% vs 42%; P = .01). The difference in proportions of patients in clinical
      remission at week 8 between the mesalazine (63%) and placebo groups was not
      significant (P = .09). The proportion of patients with histologic remission at
      week 8 was significantly higher in the budesonide group (68%) vs the mesalazine
      (26%; P = .02) or placebo (21%; P = .008) groups. The incidence of adverse events
      was 47.4% in the budesonide group, 68.4% in the mesalazine group, and 42.1% in
      the placebo group. CONCLUSIONS: In a randomized multicenter study, we found oral
      budesonide 9 mg once daily to be effective and safe for induction of clinical and
      histologic remission in patients with lymphocytic colitis, compared with placebo.
      Oral mesalazine 3 g once daily was not significantly better than placebo.
      ClinicalTrials.gov no: NCT01209208.

PMID- 30195451
TI  - Potential role for Rv2026c- and Rv2421c- specific antibody responses in
      diagnosing active tuberculosis.
AB  - The current diagnostic methods for tuberculosis (TB) have several limitations.
      Although commercial serological tests based on antibody detection are available,
      their variable accuracies limit their roles in the clinic. The aim of this study
      was to discover the improved biomarkers for TB disease by investigating the serum
      profiles of IgG and IgM antibodies against nearly all Mycobacterium tuberculosis
      (MTB) antigens in 36 active TB patients and 18 healthy controls (HCs) using
      proteome microarrays. Our results revealed that multiple antigens could induce
      stronger serum IgG or IgM responses in TB patients compared to HCs, among them,
      Rv2026c and Rv2421c were further validated by ELISA with sera from 221 samples
      and showed the moderate performance in diagnosing TB by receiver operating
      characteristic analysis. Moreover, logistic regression analysis was performed to
      establish a combined panel that provided better sensitivity and specificity at
      82.5% and 88.12%, respectively, than single antigens in the diagnosis of active
      TB. Furthermore, the antibody reactivity against Rv2026c and Rv2421c was
      correlated with clinical backgrounds. These results suggest that the combination
      of different antigens and classes of antibodies could provide promise and
      encouragement in developing an efficient serological test for the diagnosis of
      active TB.

PMID- 30195452
TI  - Longitudinal Changes in Peripapillary Retinal Nerve Fiber Layer Thickness in High
      Myopia: A Prospective, Observational Study.
AB  - PURPOSE: To determine longitudinal change of peripapillary retinal nerve fiber
      layer (pRNFL) thickness in patients with high myopia without ophthalmic disease.
      DESIGN: Prospective observational study. PARTICIPANTS: Participants were divided
      into 2 groups: a high myopia group (80 eyes) that included eyes with an axial
      length >=26.0 mm and a control group (80 eyes) that included eyes with a
      spherical equivalent (SE) between +3.0 and -6.0 diopters (D). Both groups were
      further divided into age subgroups by decade: 20s, 30s, 40s, and 50s. Each
      subgroup included 20 eyes. METHODS: After the initial visit, pRNFL thickness
      measurements were performed 2 times more with at least 1-year intervals between
      examinations using spectral-domain OCT. The mean pRNFL thickness was fitted with
      linear mixed models. MAIN OUTCOME MEASURES: The pRNFL thickness and rate of pRNFL
      thickness reduction. RESULTS: The mean patient age and thickness of the pRNFL at
      the first visit were 39.5+/-12.5 years and 90.16+/-9.06 MUm, and 41.5+/-12.2
      years and 96.80+/-9.50 MUm in the high myopia and control groups, respectively.
      The high myopia group showed a significant reduction in mean pRNFL thickness
      between the first and second visits, and between the second and third visits (P <
      0.001 and P = 0.002, respectively). For individuals aged 50 to 59 years, the
      reduction rate was -1.69 and -0.63 MUm/year in the high myopia and control
      groups, respectively; the interaction between group and duration was significant
      (P = 0.014). The reduction rate in individuals aged 40 to 49 years was -1.70 and 
      0.48 MUm/year in the 2 groups, respectively; the interaction was also significant
      (P = 0.031). Among those aged 30 to 39 years and 20 to 29 years, no such
      significant interactions were observed (-0.95 vs. -0.57 MUm/year, P = 0.086 and 
      0.31 vs. -0.19 MUm/year, P = 0.858, respectively). CONCLUSIONS: Highly myopic
      eyes had a significantly greater decrease in pRNFL over 2 years than normal eyes.
      In addition, the reduction rate of pRNFL thickness was greater in older patients
      with high myopia, whereas similar values were shown in normal controls except
      individuals aged 20 to 29 years.

PMID- 30195453
TI  - Response to: Sudden death in Parkinson's disease: Unjustifiably forgotten.

PMID- 30195454
TI  - [Self medication with Annona muricata L. (corossol) as an anti-cancer agent in
      Reunion].
AB  - INTRODUCTION: Annona muricata L. also called soursop, graviola, guanabana and
      sapoty (French creole) is a fruit tree growing in tropical countries. The fruits,
      seeds, leaves and roots are used in traditional medicine. Potential anticancer
      effects encourage patients to consume this product as self medication. The object
      of the study was to determine the prevalence of use of graviola as an anticancer
      agent by patients treated for a lung cancer. METHODS: Our survey took place in
      two thoracic oncology day cares units of the university hospital of Reunion. All
      the patients treated by chemotherapy and immunotherapy for lung cancer were asked
      the same questions in a face to face interview over a 6-month period. RESULTS:
      One hundred questionnaires were collected. Sixty seven patients consumed
      graviola. In 53.7%, graviola was consumed as an anticancer agent and 25 patients
      took it regularly. Most often graviola was ingested as an infusion of boiled
      leaves (69.5%). The supply was exclusively local. CONCLUSIONS: A quarter of
      patients treated by chemotherapy for a lung cancer in Reunion consume graviola
      regularly as self medication. The consequences of this intake, drug interactions
      and side effects are unknown and would be interesting to identify.

PMID- 30195455
TI  - Corrigendum to "Behavioral assessments of BTBR T+Itpr3tf/J mice by tests of
      object attention and elevated open platform: implications for an animal model of
      psychiatric comorbidity in autism" [Behav. Brain Res. 347 (2018) 140-147].

PMID- 30195456
TI  - Platelet engraftment after allogenic stem cell transplantation is monitoredby
      digital polymerase chain reaction without interferencebyplatelet support.
AB  - Platelet engraftment after allogeneic hematopoietic stem cell transplantation is
      conventionally monitored by daily platelet counts. Platelet transfusions are
      frequently required and obscure the detection of platelet engraftment. Digital
      polymerase chain reaction (ddPCR) of mitochondrial DNA isolated from platelets
      reliably quantifies circulating platelets derived from the stem cell graft and
      allows us to distinguish them from transfused single-donor apheresis platelets.
      In a feasibility study, consecutive daily peripheral blood samples from day 7 to
      day 20 after transplantation were analyzed by ddPCR in 22 patients after
      allogeneic transplantation. Platelet engraftment according to ddPCR was defined
      as the third of at least 3 consecutive days of increasing levels exceeding
      1000/uL endogenous platelets. Platelet counts were also assessed according to the
      engraftment cri'teria of the Center for International Blood & Marrow Transplant
      Research (CIBMTR) and the European Society for Blood and Marrow Transplantation
      (EBMT). Out of the 22 patients, five did not achieve platelet engraftment within
      20days by any of the predefined criteria. A subgroup of nine patients did show
      platelet engraftment by all three definitions. In five patients, engraftment was
      detectable according to ddPCR and EBMT, whereas in three patients, platelet
      engraftment within 20days was only confirmed by ddPCR. The detailed findings
      suggest that the day of platelet engraftment according to the EBMT criteria
      closely reflected the ddPCR detection of transplantation-derived platelets. The
      results from this feasibility study demonstrate that ddPCR offers a sensitive
      approach to detect platelet engraftment reliably and without interference from
      the individual noise of platelet counts due to platelet transfusions.

PMID- 30195457
TI  - Intraoperative factors associated with free flap failure in the head and neck
      region: a four-year retrospective study of 216 patients and review of the
      literature.
AB  - The aim of this study was to identify intraoperative factors associated with free
      flap failure. The outcomes of 216 patients (220 flaps) were analyzed
      retrospectively. A statistical analysis was performed to determine the
      association of flap failure with the intraoperative factors of prolonged
      operation time, flap type, vascular pedicle at the recipient site, and use of
      vasoactive medication. A review of the recent literature was also conducted to
      identify other intraoperative risk factors. Univariate regression analysis
      revealed that a prolonged operative time (P=0.013) and the vascular pedicle at
      the recipient site (P=0.027) were primary risk factors for flap failure.
      Furthermore, the intraoperative use of papaverine improved the success rate of
      free flap transfer (P=0.015). Multivariate regression analysis showed that only
      the application of papaverine remained statistically significant (P=0.011). The
      results confirmed that the choice of flap type had no influence on free flap
      survival (P=0.583). In addition, the literature review showed that excessive
      intraoperative fluid administration is a risk factor for free flap failure. These
      conclusions may provide microvascular surgeons with information to reduce the
      failure rate. Also, microvascular surgeons should always consider the details of
      intraoperative fluid management.

PMID- 30195458
TI  - Diagnostic criteria in Pai syndrome: results of a case series and a literature
      review.
AB  - Pai syndrome was originally described as the association of a midline cleft lip,
      midline facial polyps, and lipoma of the central nervous system. However, only a
      few patients present with the full triad, and most exhibit a wide spectrum of
      phenotypic variability. The aim of this study was to phenotypically delineate Pai
      syndrome and to propose new criteria to facilitate a clinical diagnosis in the
      future. The study cohort consisted of seven case patients and an additional 60
      cases diagnosed with Pai syndrome identified in a literature review. Only 23 of
      67 patients presented the full triad as historically described by Pai et al.
      (1987). A congenital facial midline skin mass was always encountered,
      particularly affecting the nasal structures (60/67). A midline facial cleft was
      reported in 45 of 67 patients and a pericallosal lipoma in 42 of 67 patients. The
      proposed definition of Pai syndrome is the association of (1) a congenital nasal
      and/or mediofrontal skin mass and/or a mid-anterior alveolar process polyp as a
      mandatory criterion, and at least one of the following criteria: (2) midline
      cleft lip and/or midline alveolar cleft, and/or (3) a pericallosal lipoma or
      interhemispheric lipoma in the case of corpus callosum dysgenesis.

PMID- 30195459
TI  - Acute-on-chronic liver failure vs. traditional acute decompensation of cirrhosis.

PMID- 30195460
TI  - Modelling cavitation during drop impact on solid surfaces.
AB  - The impact of liquid droplets on solid surfaces at conditions inducing cavitation
      inside their volume has rarely been addressed in the literature. A review is
      conducted on relevant studies, aiming to highlight the differences from non
      cavitating impact cases. Focus is placed on the numerical models suitable for the
      simulation of droplet impact at such conditions. Further insight is given from
      the development of a purpose-built compressible two-phase flow solver that
      incorporates a phase-change model suitable for cavitation formation and collapse;
      thermodynamic closure is based on a barotropic Equation of State (EoS)
      representing the density and speed of sound of the co-existing liquid, gas and
      vapour phases as well as liquid-vapour mixture. To overcome the known problem of
      spurious oscillations occurring at the phase boundaries due to the rapid change
      in the acoustic impedance, a new hybrid numerical flux discretization scheme is
      proposed, based on approximate Riemann solvers; this is found to offer numerical
      stability and has allowed for simulations of cavitation formation during drop
      impact to be presented for the first time. Following a thorough justification of
      the validity of the model assumptions adopted for the cases of interest,
      numerical simulations are firstly compared against the Riemann problem, for which
      the exact solution has been derived for two materials with the same velocity and
      pressure fields. The model is validated against the single experimental data set
      available in the literature for a 2-D planar drop impact case. The results are
      found in good agreement against these data that depict the evolution of both the
      shock wave generated upon impact and the rarefaction waves, which are also
      captured reasonably well. Moreover, the location of cavitation formation inside
      the drop and the areas of possible erosion sites that may develop on the solid
      surface, are also well captured by the model. Following model validation,
      numerical experiments have examined the effect of impact conditions on the
      process, utilizing both planar and 2-D axisymmetric simulations. It is found that
      the absence of air between the drop and the wall at the initial configuration can
      generate cavitation regimes closer to the wall surface, which significantly
      increase the pressures induced on the solid wall surface, even for much lower
      impact velocities. A summary highlighting the open questions still remaining on
      the subject is given at the end.

PMID- 30195461
TI  - Clinical Features of Central Serous Chorioretinopathy With Type 1 Choroidal
      Neovascularization.

PMID- 30195462
TI  - HIV infection and care pathway: From guidelines to clinical practice.
AB  - OBJECTIVES: To quantify within a cohort of HIV-infected individuals the number of
      medical visits and procedures to be carried out according to comorbidities and
      risk factors to implement a personalized care pathway. PATIENTS AND METHODS:
      Retrospective study of 915 patients consulting from January 1 to December 31,
      2016 at an outpatient unit of multidisciplinary consultations, using an
      electronic patient record. We built an algorithm using parameters required for
      the application of the national guidelines for the management of HIV-infected
      individuals. The frequency of comorbidities was measured according to gender,
      transmission risk group, and nadir CD4 (<or>200/mm3). RESULTS: Patients were
      mostly men (median age: 52 years), of whom 16% were aged>=60 years. Viral load
      was<40 copies/mL in 93.5% of treated patients and CD4 cell count>=500/mm3 for
      73%. Overall, 74.5% of patients had at least one comorbidity. The number of
      comorbidities was similar in men and women but was significantly higher in
      patients with a nadir CD4 <200/mm3 and increased with age (irrespective of
      gender). The minimum number of consultations to be scheduled per year was 8123:
      70% for the management of comorbidities with an average of six
      consultations/year/patient. Overall, 53% of patients should attend a proctology
      consultation. The minimum number of paramedical procedures to be performed was
      5115. CONCLUSION: The implementation of a personalized multidisciplinary
      management within a single facility seems to be a suitable care model to address
      the needs of HIV-infected individuals.

PMID- 30195463
TI  - miR-301a expression: Diagnostic and prognostic marker for prostate cancer.
AB  - BACKGROUND: Prostate-specific antigen screening for prostate cancer (CaP) remains
      controversial. This study establishes the role of microRNA 301a (miR-301a) as a
      supplemental biomarker that can distinguish between patients with benign prostate
      hyperplasia and clinically significant CaP. We evaluate the ability of miR-301a
      to predict the adverse pathology of CaP. METHODS: In the first cohort, serum and
      prostate tumor samples were obtained from thirteen patients with Benign prostate
      hyperplasia (BPH), twelve patients with Gleason 6, and sixteen patients with
      Gleason 7 prostate adenocarcinoma. In the second cohort, 40 prostatectomy cases
      were selected (BPH:12, Gleason 6:12 and Gleason 7:16). MiRNA was extracted from
      serum and tumor samples. Quantitative reverse transcription-polymerase chain
      reaction was performed for detection of miR-301a. To understand the molecular
      role of miR-301a, we performed cell viability, Western blots, promoter analysis,
      overexpression, and silencing studies in BPH and DU-145 cell lines. RESULTS: MiR
      301a demonstrated a significantly higher expression in both serum and tumor
      tissue in patients with CaP when compared to patients with BPH (P = 0.011 and
      0.013 for serum and tissue expression, respectively). Expression of miR-301a in
      prostatectomy specimens correlated with increased Gleason score. We demonstrated
      that miR-301a inhibited the pro-apoptotic function of RUNX3, and activated ROCK1
      mediated pro-survival signal in CaP. Silencing miR-301a initiated the pro
      apoptotic function of RUNX3 by inhibiting ROCK1 expression in CaP cells.
      CONCLUSIONS: Expression of miR-301a could be a valuable adjunct tool for
      stratifying patients with elevated prostate-specific antigen, as well as those
      diagnosed with CaP. Including the miR-301a as an additional variable in MSKCC
      post-prostatectomy nomogram improved its ability in facilitating clinical
      decision-making.

PMID- 30195464
TI  - Feasibility of sub-dermal soft tissue deformation assessment using B-mode
      ultrasound for pressure ulcer prevention.
AB  - Pressure Ulcer (PU) prevention remains a main public health issue. The physio
      pathology of this injury is not fully understood, and a satisfactory therapy is
      currently not available. Recently, several works suggested that mechanical
      strains are responsible of deformation-induced damage involved in the initiation
      of Deep Tissue Injury (DTI). A better assessment of the internal behavior could
      allow to enhance the modeling of the transmission of loads into the different
      structures composing the buttock. A few studies focused on the experimental in
      vivo buttock deformation quantification using Magnetic Resonance Imaging (MRI),
      but its use has important drawbacks. In clinical practice, ultrasound imaging is
      an accessible, low cost, and real-time technic to study the soft tissue. The
      objective of the present work was to show the feasibility of using B-mode
      ultrasound imaging for the quantification of localised soft-tissue strains of
      buttock tissues during sitting. An original protocol was designed, and the intra
      operator reliability of the method was assessed. Digital Image Correlation was
      used to compute the displacement field of the soft tissue of the buttock during a
      full realistic loading while sitting. Reference data of the strains in the
      frontal and sagittal planes under the ischium were reported for a population of 7
      healthy subjects. The average of shear strains over the region of interest in the
      fat layer reached levels up to 117% higher than the damage thresholds previously
      quantified for the muscular tissue in rats. In addition, the observation of the
      muscles displacements seems to confirm previous results which already reported
      the absence of muscular tissue under the ischium in the seated position,
      questioning the assumption commonly made in Finite Element modeling that deep
      tissue injury initiates in the muscle underlying the bone.

PMID- 30195465
TI  - Ganglion Impar block improves neuropathic pain in coccygodynia: A preliminary
      report.
AB  - AIM OF THE STUDY: To define the effectiveness of ganglion Impar block in
      improving neuropathic pain. MATERIALS AND METHODS: Patients who had pain around
      the coccyx for more than three months and did not respond to conservative
      treatment were included in this study. All the patients underwent fluoroscopy
      guided transsacrococcygeal ganglion Impar block with injecting 3 mL of 0.5%
      bupivacaine, 2 mL saline, and 1 mL (40 mg) of methylprednisolone. Patients were
      evaluated with visual analog scale (VAS) for pain, Leeds assessment of
      neuropathic symptoms and signs scale (LANSS) for neuropathic pain, Beck
      depression Inventory (BDI) for mood and Short-form 12 (SF-12) for quality of life
      before, 1 month 3 months and 6 months after the injection. Patients' painless
      sitting duration was also recorded. RESULTS: A total of 28 patients were included
      in the final analyses. VAS and LANSS scores improved significantly throughout the
      follow-up periods. BDI scores also improved while SF-12 scores did not show
      significant changes. Painless sitting period of the patients' improved
      significantly. CONCLUSIONS: Ganglion Impar block is effective in decreasing the
      neuropathic component of chronic coccygodynia. This improves painless sitting in
      patients but its reflections on quality of life is not clear.

PMID- 30195466
TI  - Formyl-Peptide Receptors in Infection, Inflammation, and Cancer.
AB  - Formyl-peptide receptors (FPRs) recognize bacterial and mitochondrial formylated
      peptides as well as endogenous non-formylated peptides and even lipids. FPRs are
      expressed on various host cell types but most strongly on neutrophils and
      macrophages. After the discovery of FPRs on leukocytes, it was assumed that these
      receptors predominantly govern a proinflammatory response resulting in
      chemotaxis, degranulation, and oxidative burst during infection. However, it is
      clear that the activation of FPRs has more complex consequences and can also
      promote the resolution of inflammation. Recent studies have highlighted
      associations between FPR function and inflammatory conditions, including
      inflammatory disorders, cancer, and infection. In this review we discuss these
      recent findings.

PMID- 30195467
TI  - Hiding in Plain Sight: Soluble Immunomodulatory Receptors.
AB  - Alternatively spliced natural soluble isoforms of immunomodulatory receptors
      [cytotoxic T lymphocyte antigen-4 (CTLA-4), 4-1BB, and programmed death-1 (PD
      1)/PD-L1] have been overlooked in favor of their cell-surface-bound counterparts
      that have generated blockbuster antibodies for the treatment of cancer. We
      propose that the soluble variants of these receptors contribute to immune
      regulation and offer potential as targets for immunotherapy.

PMID- 30195468
TI  - Radiotherapy is a safe and effective salvage treatment for recurrent cervical
      cancer.
AB  - OBJECTIVE: The feasibility of salvage radiotherapy (RT) for patients with
      recurrent cervical cancer after definitive treatment is contentious. The purpose
      of this study was to investigate the feasibility and benefit of RT, particularly
      intensity-modulated RT (IMRT), for salvage treatment in patients with recurrent
      cervical cancer. METHODS: We retrospectively analyzed 125 patients with recurrent
      cervical cancer treated with RT at Yonsei Cancer Center between January 2007 and
      December 2016. All patients received salvage RT for the recurred or metastatic
      tumor mass. Irradiating dose and volume were determined depending on initial
      treatment. IMRT was selected in challenging cases, such as re-irradiation or for
      patients for whom implementing a satisfactory 3-dimensional conformal RT plan was
      challenging. RESULTS: The median follow-up period was 5.5 years (range, 10.8
      months to 41 years). The 5-year local failure-free survival (LFFS) and
      progression-free survival (PFS) rates were 63.9% and 39.6%, respectively. The 5
      year overall survival (OS) rate was 66%; 10-year OS reached 51%. The median PFS
      rates in patients with locoregional failure, distant metastases, or both were
      45.4, 29.1, and 14.7 months, respectively (p = 0.005). For the 45 patients that
      received re-irradiation, 5-year LFFS, PFS, and OS rates were 47.1%, 33.2%, and
      66.5%, respectively. Late complications were observed in 12 patients (12/125,
      9.6%). CONCLUSIONS: Our data suggest that salvage RT is safe and effective
      against recurrent cervical cancer. IMRT is a safe and effective salvage modality
      for these patients, including those requiring re-irradiation.

PMID- 30195469
TI  - Interannual variation in UV-B and temperature effects on bud phenology and growth
      in Populus tremula.
AB  - Warming affects phenological processes such as spring bud break and autumnal bud
      set, and also growth rates of trees. Recently, it has been shown that these
      physiological processes also may be influenced by the ultraviolet-B (UV-B) part
      of the solar spectrum, and there are reasons to expect that the two environmental
      factors induce interactive effects when acting in concert. In this study, our aim
      was to elucidate how experimental enhancements in temperature and UV-B, alone and
      in combination, affect growth and seasonal phenology of Eurasian aspen (Populus
      tremula) over several growing seasons (three years). Moreover, we tested how
      environmentally induced changes in phenology affect the growth achieved over each
      season, that is, the importance of a prolonged growing season for growth yield.
      The plants grew in an outdoor experiment with modulated enhancements of
      temperature and UV-B during the growing season. Both UV-B and temperature
      enhancement affected bud set dates, while bud break dates were only affected by
      temperature enhancement. Temperature delayed bud set in all years, but gradually
      less over years, while UV-B yielded earlier bud set the first year but showed a
      delayed response the following years. Bud break was always earlier under
      temperature enhancement. The experimentally induced extension of the growing
      season in both ends had a positive effect of growth throughout the three-year
      period. However, the reduced responsiveness of bud set to both enhancement
      treatments suggest that the plants gradually acclimated to the modified climate,
      a finding that should also be investigated for other tree species.

PMID- 30195470
TI  - Hypersensitivity reactions with prolonged infusions of beta-lactams?

PMID- 30195471
TI  - Prioritizing research areas for antibiotic stewardship programmes in hospitals: a
      behavioural perspective consensus paper.
AB  - SCOPE: Antibiotic stewardship programmes (ASPs) are necessary in hospitals to
      improve the judicious use of antibiotics. While ASPs require complex change of
      key behaviours on individual, team organization and policy levels, evidence from
      the behavioural sciences is underutilized in antibiotic stewardship studies
      across the world, including high-income countries (HICs). A consensus procedure
      was performed to propose research priority areas for optimizing effective
      implementation of ASPs in hospital settings using a behavioural perspective.
      METHODS: A workgroup for behavioural approaches to ASPs was convened in response
      to the fourth call for leading expert network proposals by the Joint Programming
      Initiative on Antimicrobial Resistance (JPIAMR). Eighteen clinical and academic
      specialists in antibiotic stewardship, implementation science and behaviour
      change from four HICs with publicly funded healthcare systems (e.g. Canada,
      Germany, Norway and the UK) met face-to-face to agree on broad research priority
      areas using a structured consensus method. Question addressed and
      recommendations: The consensus process assessing the ten identified research
      priority areas resulted in recommendations that need urgent scientific interest
      and funding to optimize effective implementation of ASPs for hospital inpatients
      in HICs with publicly funded healthcare systems. We suggest and detail
      behavioural science evidence-guided research efforts in the following areas: (a)
      comprehensively identifying barriers and facilitators to implementing ASPs and
      clinical recommendations intended to optimize antibiotic prescribing; (b)
      identifying actors ('who') and actions ('what needs to be done') of ASPs and
      clinical teams; (c) synthesizing available evidence to support future research
      and planning for ASPs; (d) specifying the activities in current ASPs with the
      purpose of defining a control group for comparison with new initiatives; (e)
      defining a balanced set of outcomes and measures to evaluate the effects of
      interventions focused on reducing unnecessary exposure to antibiotics; (f)
      conducting robust evaluations of ASPs with built-in process evaluations and
      fidelity assessments; (g) defining and designing ASPs; (h) establishing the
      evidence base for impact of ASPs on resistance; (i) investigating the role and
      impact of government and policy contexts on ASPs; and (j) understanding what
      matters to patients in ASPs in hospitals. CONCLUSIONS: Assessment, revisions and
      updates of our priority-setting exercise should be considered at intervals of 2
      years. To propose research priority areas in low- and middle-income countries,
      the methodology reported here could be applied.

PMID- 30195472
TI  - Pasteurella multocida multiple intrapelvic abscesses in a young woman with
      uterine cervical cancer.
AB  - Pasteurella multocida, a zoonotic pathogen in humans, is known to be associated
      with skin and soft tissue infections following animal bites, but rarely causes
      visceral infections. We report a case of P. multocida-associated multiple
      intrapelvic abscesses in a young woman with uterine cervical cancer. A 29-year
      old unmarried woman was referred to us because of prolonged high fever
      accompanying abdominal pain with muscular guarding. She had a domestic cat but
      denied of any bites or scratches before that. Computed tomography demonstrated
      ascites and multiple abscesses around her uterus. Her condition did not improve
      with an initial treatment with flomoxef, clindamycin, and azithromycin. Further,
      we performed percutaneous pus drainage and switched the antimicrobial therapy to
      a combination of piperacillin/tazobactam and minocycline for 10 days. Although P.
      multocida was isolated from vaginal culture, no organisms were isolated from the
      pus culture. However, further investigation with specimen-direct 16S rDNA
      analysis diagnosed P. multocida as possibly a single pathogen responsible for the
      intrapelvic infection. After taking oral levofloxacin for two weeks, no
      recurrence was reported. Although P. multocida is known as an animal-related
      pathogen, it can transmit to humans without apparent bites or scratches. The
      present case illustrates that P. multocida can cause intrapelvic abscess as a
      result of ascending genital infection.

PMID- 30195473
TI  - Successful voriconazole treatment of Talaromyces marneffei infection in an HIV
      negative patient with osteolytic lesions.
AB  - Talaromyces marneffei (T. marneffei) is a dimorphic fungus that causes systemic
      infection in immunocompromised patients. Here, we present a case of T. marneffei
      infection in an immunocompetent patient with an osteolytic lesion. Diagnosis was
      established by fungal culture. The patient responded rapidly to intravenous
      voriconazole, followed by oral voriconazole. We reviewed 18 reported cases of T.
      marneffei infection with osteolytic lesions, which suggests a much higher rate of
      osteolytic lesions in immunocompetent patients than previously thought.

PMID- 30195474
TI  - cGMP-dependent protein kinase I (cGKI) modulates human hepatic stellate cell
      activation.
AB  - BACKGROUND: The activation of hepatic stellate cells (HSCs) plays a crucial role
      in liver fibrosis, however the role of HSCs is less understood in hepatic insulin
      resistance. Since in the liver cGMP-dependent protein kinase I (cGKI) was
      detected in HSC but not in hepatocytes, and cGKI-deficient mice that express cGKI
      selectively in smooth muscle but not in other cell types (cGKI-SM mice) displayed
      hepatic insulin resistance, we hypothesized that cGKI modulates HSC activation
      and insulin sensitivity. MATERIALS AND METHODS: To study stellate cell activation
      in cGKI-SM mice, retinol storage and gene expression were studied. Moreover, in
      the human stellate cell line LX2, the consequences of cGKI-silencing on gene
      expression were investigated. Finally, cGKI expression was examined in human
      liver biopsies covering a wide range of liver fat content. RESULTS: Retinyl-ester
      concentrations in the liver of cGKI-SM mice were lower compared to wild-type
      animals, which was associated with disturbed expression of genes involved in
      retinol metabolism and inflammation. cGKI-silenced LX2 cells showed an mRNA
      expression profile of stellate cell activation, altered matrix degradation and
      activated chemokine expression. On the other hand, activation of LX2 cells
      suppressed cGKI expression. In accordance with this finding, in human liver
      biopsies, we observed a negative correlation between cGKI mRNA and liver fat
      content. CONCLUSIONS: These results suggest that the lack of cGKI possibly leads
      to stellate cell activation, which stimulates chemokine expression and activates
      inflammatory processes, which could disturb hepatic insulin sensitivity.

PMID- 30195475
TI  - Molecular phylogenetics of Aspidiotini armored scale insects (Hemiptera:
      Diaspididae) reveals rampant paraphyly, curious species radiations, and multiple
      origins of association with Melissotarsus ants (Hymenoptera: Formicidae).
AB  - The armored scale insect tribe Aspidiotini comprises many pest species that are
      globally invasive and economically damaging. The taxonomy of scale insects is
      based almost solely upon morphological characters of adult females, and little
      prior work has been done to test the classification of aspidiotines against
      molecular evidence. To address these concerns, we reconstruct a molecular
      phylogeny for aspidiotine armored scales that expands greatly upon taxonomic and
      character representations from previous studies. Our dataset includes 127 species
      (356 terminal taxa) and four gene regions: 28S, EF-1alpha, COI-COII, and CAD.
      Nearly 50% of the species treated are identified as pests and several more may
      represent emerging pests. Phylogenetic data were analyzed in a Bayesian framework
      using MC3 iterations. The majority of sampled aspidiotine genera are not
      monophyletic as currently defined. Monophyly constraints for 'worst offenders'
      were imposed on the phylogeny and stepping-stone MCMC was performed to calculate
      marginal likelihood scores. Comparisons of marginal likelihoods from runs with
      constrained vs. informative priors support the interpretation that pest-rich
      genera are not monophyletic. We use character mapping to illustrate signal and
      convergence for selected traits that have been used to define or recognize genera
      and evaluate consistency and retention indices for these traits. The phylogeny
      illustrates a pervasive pattern in which extremely polyphagous pests - typically
      having large populations and wide geographical distributions - are frequently
      intertwined with range-limited specialists on the phylogeny. Finally, the
      phylogeny recovers three origins of ant association among the Aspidiotini. The
      history of ant/diaspidid symbioses involves periods of sustained partner
      fidelity, spanning multiple speciation events, which have been punctuated by
      opportunistic switches to novel partners.

PMID- 30195476
TI  - Cryptic divergences in the genus Pisum L. (peas), as revealed by phylogenetic
      analysis of plastid genomes.
AB  - Organellar genomes may shed light on complicated patterns of plant evolution at
      inter- and intraspecies level. Primary structure of plastid genomes sequenced in
      this study and taken from public databases was characterised and compared in 22
      diverse, mostly wild representatives of the genus Pisum (peas). Phylogenetic
      trees reconstructed via Bayesian approach on the basis of entire plastid genomes
      resembled those reconstructed on the basis of a nuclear gene His5 coding for a
      minor histone H1 subtype. They reveal Pisum fulvum as an early divergence of the
      genus but do not support other taxonomical subdivisions. The positions of three
      accessions, classified as P. sativum subsp. elatius (the wild subspecies of the
      common pea), appeared quite unexpected. On the entire plastid genome tree, two
      accessions, from the Black Sea area of Turkey and Georgia, clustered with
      representatives of another species, P. fulvum, while the other, from Greece, was
      the first divergence of the P. sativum branch. We suppose these unusual plastid
      genomes to be ancient lineages ascending to a 'missing link' between P. fulvum
      and P. sativum, represented by accession Pe 013 from Turkey. Accessions with
      common pea appearance but deeply diverged plastids could occur through occasional
      crossing of diverged pea lines in the past and biparental plastid inheritance,
      both events being possible in peas.

PMID- 30195477
TI  - Phylogenomics, biogeography, and adaptive radiation of grapes.
AB  - The application of whole-genome resequencing based on next-generation sequencing
      technologies provides an unprecedented opportunity for researchers to resolve
      long-standing evolutionary problems. Taxa belonging to the grape genus (Vitis L.)
      represent important genetic resources for the improvement of cultivated grapes.
      However, it has been challenging to resolve the deep phylogenetic relationships
      within Vitis, limiting the current understanding of the evolutionary history of
      Vitis and preventing the use of valuable wild grape resources. In this study, we
      obtained whole-genome sequence data from 41 accessions representing most taxa
      within subgenus Vitis and aligned these sequences to the Vitis vinifera L.
      reference genome. We reconstructed deep phylogenetic relationships within
      subgenus Vitis based on 2068 single-copy orthologous genes, which led to a robust
      topology with bootstrap support values of 100% for almost all branches. Three
      main clades are recovered within subgenus Vitis reflecting their continental
      distribution through North America, Europe, and East Asia, respectively. Our
      results suggest that the most possible migration route of the East Asian Vitis is
      from northeastern Asia southward to South Asia and Southeast Asia. The East Asian
      Vitis seems to have experienced adaptive radiation during the Miocene. This study
      provides novel insights into the diversification history of the grape genus
      Vitis.

PMID- 30195478
TI  - Comparative transcriptome analysis of Paphia undulata with different foot colors.
AB  - Foot color is an important trait in Paphia undulata that influences consumer
      selection. To elucidate the molecular basis of foot color, six transcriptome
      libraries of P. undulata with different foot colors were constructed: white (L2,
      L3 and L4) and orange (D2, D3, D4). There is a significant difference in color
      index (L*, a*, b*) between the two groups (P < 0.05). These six paired-end
      libraries were sequenced using the Illumina HiSeq 2500 platform. In total, 48.22
      Gb of clean data were obtained and de novo assembled into 58,159 unigenes with a
      mean length of 889.51 bp and N50 of 1461 bp. A total of 19,070 unigenes were
      significantly matched to known unique proteins. The Gene Ontology (GO) annotation
      and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to determine
      metabolic pathways and candidate genes associated with foot color traits.
      Compared with white P. undulate, a total of 107 transcripts were identified as
      differentially expressed genes (DEGs) in orange samples using Cuffdiff, including
      74 up-regulated and 33 down-regulated genes. Of these differentially expressed
      genes, many were involved in the synthesis and transport of carotenoids and
      pigment biosynthesis. Additionally, results of the transcriptome analysis were
      verified by quantitative real-time PCR (qRT-PCR). Overall, this experiment
      discovered several potential foot coloration genes and related molecular
      mechanisms using RNA-seq, which paves the way for further functional elucidation
      of color-related genes and assists selective breeding practices in P. undulata.

PMID- 30195479
TI  - The role of linear endosonography for the diagnosis of acute pancreatitis when
      other methods failed.
AB  - BACKGROUND AND STUDY AIMS: Acute pancreatitis has no obvious cause after
      clinical, laboratory and radiologic investigation in 10%-30% of patients, and the
      diagnosis of idiopathic pancreatitis is given. This study investigated the role
      of linear EUS for identification of possible causes for acute pancreatitis when
      other investigative methods failed. PATIENTS AND METHODS: Between June 2012 and
      March 2017, 35 patients [25 women; mean age: 51.9 + 17.8 years] with idiopathic
      acute pancreatitis underwent linear EUS for investigation. All of these cases
      were contacted for a follow-up telephone interview to compare the EUS findings
      with the final diagnosis and outcome. RESULTS: Pancreaticobiliary abnormalities
      were identified in 19 of 35 (54.3%) patients. Ten (28.6%) patients had
      microlithiasis or biliary sludge. Microlithiasis and choledocholithiasis were
      identified in 8 (22.8%) and a single (2.8%) patient, respectively. Two patients
      presented gallbladder biliary sludge, one of them with microlithiasis. Chronic
      pancreatitis was found on EUS in 6 (17.1%) patients, and pseudotumoral masses
      confirmed by EUS-FNA as autoimmune pancreatitis were detected in other 3 (8.6%)
      cases. Linear EUS was normal in 13 (37.1%) patients, and demonstrated findings of
      recent acute pancreatitis but no other etiological factor in 3 (8.6%) cases.
      After a mean follow-up of 33.3 months, no case with a normal EUS evaluation
      presented a new episode of pancreatitis, 1 of 9 cases with microlithiasis
      presented an episode of recurrent pancreatitis due to choledocolithiasis after
      cholecystectomy, and 3 of 9 cases with chronic pancreatitis presented recurrent
      episodes, including the 2 cases of autoimmune pancreatitis. CONCLUSIONS: Linear
      EUS provides diagnostic information in approximately a half of patients with
      idiopathic acute pancreatitis. Exclusion of pancreaticobiliary abnormalities on
      EUS has an important prognostic value for absence of new episodes of acute
      pancreatitis.

PMID- 30195480
TI  - Small bowel lymphangioma.

PMID- 30195481
TI  - Understanding the relationship between BMI and sexual dysfunction: Can DSM-5 shed
      light into this topic?
AB  - INTRODUCTION: The links between body weight and sexuality, notably sexual
      dysfunction (SD), are intricate and not yet fully understood. A more individual
      focused evaluation of sexual difficulties, as recently provided by the Diagnostic
      and Statistical Manual of Mental Disorders (DSM-5), contributes to improve
      precision in SD diagnosis and has the potential to advance our knowledge on the
      association between body weight and SD. OBJECTIVES: To identify gender
      differences in sexual behaviors and SD among Portuguese men and women within
      different classes of body mass index (BMI); and to explore the association
      between BMI and SD by using the new DSM-5 criteria. MATERIAL AND METHODS: Face-to
      face interviews followed by self-completed questionnaires of primary healthcare
      users in Portugal (n=323). Data on sociodemographic variables, BMI, sexual
      behaviors and SD were collected. DSM-5 criteria were used to assess sexual
      dysfunction. The International Index of Erectile Function (IIEF) and the Female
      Sexual Function Index (FSFI) for men and women, respectively, were used for
      comparison purposes. RESULTS: Overweight and obese women reported less sexual
      partners, less satisfaction with sexual frequency and rated sexual life as less
      important. These differences were not found among men. Normal weight men and
      women had a higher score of IIEF and FSFI, respectively, than those overweight
      and obese. No significant effects of BMI scale on SD following DMS-5 were
      detected. CONCLUSIONS: Women's sexual function is more impacted by BMI than
      men's. Individual-orientated approaches, as proposed in DSM-5, may allow a better
      understanding on the relation between body size and sexuality in both genders.

PMID- 30195482
TI  - Prevalence and incidence of clinically diagnosed Alzheimer's disease dementia
      from 1994 to 2012 in a population study.
AB  - INTRODUCTION: The trends in prevalence and incidence of Alzheimer's disease (AD)
      dementia remain uncertain. METHODS: A sample of 2794 participants with a clinical
      diagnosis for AD dementia were included. RESULTS: The 2010 census standardized
      prevalence of AD dementia was 14.5% (95% CI = 13.7-15.3), and annual incidence
      was 2.3% (1.7-2.9). Both prevalence and incidence showed substantial variation
      over time, but no secular trends. The prevalence of AD dementia did not change
      significantly from 14.6% (95% CI = 13.0, 16.2) in 1994-1997 to 14.7% (95% CI =
      13.2, 16.2) in 2010-2012 (P = .84). The annual incidence of AD dementia was 2.8%
      (95% CI = 2.2, 3.2) in 1998-2000 and 2.2% (95% CI = 1.6, 2.8) in 2004-2006 (P =
      .20) and remained steady in 2010-2012. The prevalence and incidence among African
      Americans were approximately twice than those among European Americans.
      CONCLUSIONS: The prevalence and incidence of AD dementia showed substantial
      variation between 1994 and 2012, but no secular trend.

PMID- 30195483
TI  - PCOS: update and diagnostic approach.

PMID- 30195484
TI  - Dysregulated serum metabolites in staging of hepatocellular carcinoma.
AB  - BACKGROUND: Correct staging of hepatocellular carcinoma (HCC) could help
      physicians to precisely select treatments for patients, such as surgery,
      chemotherapy, or their combination. The objective of this study was to explore
      potential metabolic markers for staging of hepatocellular carcinoma. METHODS: By
      liquid chromatography with mass spectrometry (LC-MS), the serum metabolic
      profiles of 60 pathologically confirmed hepatocellular carcinoma (HCC) patients
      were analyzed using the TNM staging system and Chinese staging system. RESULTS:
      The serum levels of dihydrocortisol, lysophosphatidylcholine (LPC-18:0),
      lysophosphatidylethanolamine (LPE-16:0), taurine, uric acid, adipic acid,
      tetracosatetraenoic acid, and L-octanoylcarnitine differed significantly between
      staging I and non-stage I HCCs (p < 0.05) based on the HCC TNM staging system,
      and compared to stage I sera, non-stage I sera contained higher levels of
      dihydrocortisol, adipic acid, tetracosatetraenoic acid, and L-octanoylcarnitine.
      There are significant differences were observed in serum levels of LPC (22:6),
      alpha-linolenylcarnitine, estrone, LPE (16:0), LPE (18:2), and taurine between
      stage I and stage II HCCs (p < 0.05) based on the Chinese HCC staging system, and
      compared to stage I sera, stage II sera had a higher level of LPC (22:6).
      CONCLUSION: These dysregulated metabolites in sera of HCC patients potentially
      could be used as biomarkers for the clinical staging of HCC.

PMID- 30195485
TI  - Protection in sheep against heterologous challenge with serotype Asia-1 foot-and
      mouth disease virus using high potency vaccine.
AB  - Foot-and-mouth disease virus (FMDV) serotype Asia-1 is prevalent in countries
      considered high risk for incursion into Australia, and has recently been
      responsible for a number of outbreaks in India, Bangladesh, Pakistan and Turkey.
      In vitro vaccine matching has shown a number of contemporary FMDV Asia-1 strains
      vary antigenically to the Asia-1 Shamir vaccine strain, which could result in
      poor protection with use of this vaccine. Therefore it was important to test the
      ability of the Asia-1 Shamir vaccine to protect sheep from challenge with a
      recent, heterologous strain at different days post-vaccination (dpv), including
      in an emergency vaccination scenario (challenge 4 or 7 dpv). Sheep (5 per group)
      were challenged with the Asia-1/PAK/19/2014 isolate by intra-nasopharyngeal
      instillation 21 (V21), 7 (V7) or 4 (V4) dpv with high-potency (>6 PD50) Asia-1
      Shamir vaccine. An additional five sheep were mock-vaccinated with adjuvant only
      (antigen-free preparation) 4 days prior to challenge (A4), and five unvaccinated
      (UV) control sheep were also challenged. All V21, V7 and V4 sheep were protected
      from clinical FMD. Eighty percent of V21 sheep and 40% of V7 sheep had sterile
      immunity, however all V4 sheep became systemically infected. Vaccination reduced
      excretion of virus in nasal and oral secretions but had no effect on the
      development of persistent infection. All A4 sheep and UV control sheep developed
      clinical FMD. The high-potency Asia-1 Shamir vaccine will protect against disease
      should an outbreak of contemporary Asia-1 viruses occur. Intranasopharyngeal
      instillation is an effective challenge method for use in vaccine efficacy studies
      in sheep.

PMID- 30195486
TI  - High-dose influenza vaccine use among patients receiving hemodialysis in the
      United States, 2010-2013.
AB  - BACKGROUND: Standard influenza vaccines may be of limited benefit to patients
      with end-stage renal disease (ESRD). These patients may benefit from high-dose
      influenza vaccine, currently indicated for patients aged >=65 years. Studies in
      other populations have demonstrated that high-dose vaccine elicits a stronger
      immunological response. We compared vaccine uptake in the United States and
      predictors of receipt for high-dose and standard influenza vaccines. METHODS:
      Using data from the United States Renal Data System (2010-2013), we conducted a
      cohort study of 421,482 adult patients on hemodialysis. We examined temporal
      trends in uptake of high-dose or standard trivalent influenza vaccine each
      influenza season, and used multivariate logistic regression to assess the
      association between individual-level variables (e.g., demographics,
      comorbidities) and facility-level variables (e.g., facility size and type) with
      vaccine receipt. RESULTS: The proportion of patients with ESRD who were
      vaccinated with any influenza vaccine increased from 68.3% in 2010 to 72.4% in
      2013. High-dose vaccines were administered to 0.9% of patients during the study
      period, and 16.7% of high-dose vaccines were administered to patients <65 years
      of age. Among patients aged >=65 years, older patients (>79 vs. 65-69 years: OR,
      1.29; 95% CI, 1.19-1.41) and patients at hospital-based versus free-standing
      dialysis facilities (OR, 2.31; 95% CI, 2.13-2.45) were more likely to receive
      high-dose vaccine, while blacks (vs. whites [OR, 0.66; 95% CI, 0.61-0.71]) and
      patients with longer duration of ESRD (>9 vs. 0 years: OR, 0.66; 95% CI, 0.55
      0.78) were less likely to receive the high-dose vaccine. CONCLUSIONS: While the
      overall influenza vaccination rate has increased, use of high-dose vaccine among
      patients with ESRD was very low. Being an older patient, living in the Midwest,
      and receiving care at hospital-based facilities were the strongest predictors of
      receiving high-dose vaccine.

PMID- 30195487
TI  - Non-live pentavalent vaccines after live measles vaccine may increase mortality.
AB  - Live measles vaccine (MV) may have beneficial off-target/non-specific effects
      (NSEs) reducing child mortality beyond prevention of measles infection. In
      contrast, the non-live pentavalent (Diphtheria-Tetanus-Pertussis-H. influenzae
      Type B-Hepatitis B) vaccine has no beneficial NSEs. The NSEs are strongest for
      the most recent vaccine. Hence, sequence of vaccination may affect survival. In
      Guinea-Bissau, we followed 7094 measles-vaccinated children prospectively from
      first home visit after 9 months (when MV is scheduled) to 5 years of age. We
      compared survival by sequence of MV and third Pentavalent vaccine (Penta3;
      scheduled at 31/2 months) in Cox proportional-hazards models. Compared with being
      vaccinated in-sequence (Penta3-then-MV), having received out-of-sequence Penta3
      after-MV before the visit was associated with an adjusted Hazard Ratio (aHR) of
      1.19 (95%CI: 0.84-1.69); Receiving missing Penta doses on the visit date tended
      to be associated with higher mortality (aHR = 1.87 (0.96-3.65)) while not
      receiving missing doses of Penta was not (aHR = 0.93 (0.57-1.54)), test for
      interaction p = 0.09.

PMID- 30195488
TI  - Vaccinating donors for hematopoietic cell transplantation: A systematic review
      and future perspectives.
AB  - Allogeneic hematopoietic cell transplantation (Allo-HCT) recipients are at an
      increased risk of infectious complications, which is a major cause of morbidity
      and mortality post-transplant. Vaccination of donors is one of the strategies
      that has been studied to improve immune reconstitution post-transplant, however
      the efficacy and safety of this strategy is not well reviewed in the literature.
      In this systematic review we sought to evaluate the current strategies of donor
      vaccination along with their immunogenicity, effectiveness and safety. Utilizing
      strict selection criteria with defined MeSH terminology, an electronic search was
      conducted from the following databases: Medline, Cochrane Central Register of
      Controlled Trials, Cochrane Database of Systematic Reviews and Scopus. Abstracts
      of various professional society meetings were also screened and hand searching of
      various reviews and guideline articles was carried out. The full text of 52
      articles were reviewed, from which 5 articles satisfied the inclusion/exclusion
      criteria for effectiveness and immunogenicity trials and 1 article was included
      for safety data. Jadad score was used to assess the quality of included studies.
      The results of the included studies were inconsistent, and the studies were
      generally of suboptimal methodological quality. Most of the included studies (n =
      3) investigated the use of more than one vaccine, however not all commonly used
      vaccines in HCT were investigated. None of the studies reported any long-term
      benefits for HCT recipients of vaccinated donors. Only one study reported safety
      data of using vaccination in donors. Given the suboptimal quality of the studies,
      and questionable effectiveness, donor vaccination cannot be recommended for all.
      Prospective high-quality vaccine trials in HCT donors are needed.

PMID- 30195489
TI  - Assessing the effectiveness of zoster vaccine live: A retrospective cohort study
      using primary care data in the United Kingdom.
AB  - BACKGROUND: Herpes zoster (shingles) is a common viral disease increasing in risk
      and severity with age. Post-herpetic neuralgia (PHN), a complication of shingles,
      causes severe pain impacting quality of life (QoL). Zoster Vaccine Live (ZVL), a
      licensed vaccine for the prevention of shingles in the United Kingdom (UK), is
      part of the national immunisation programme (NIP) for adults aged 70-79. Public
      Health England (PHE) reports show shingles vaccine coverage varies, but is
      typically 50-60% across eligible cohorts. MATERIALS/METHODS: This retrospective,
      matched cohort study was conducted using The Health Improvement Network (THIN) UK
      primary care database. Individuals aged 70-79 were classified based on their
      vaccination status between September 2013 and May 2016. Risk and incidence rates
      for shingles were calculated for both groups over the duration of the study (mean
      1.2 years). Vaccine effectiveness (VE) was calculated using the equation 1
      relative risk (RR) for shingles and PHN. RESULTS: Within the total cohort (n =
      295,135), 70,867 (24%) were vaccinated and 224,268 (76%) were unvaccinated. 2435
      (0.83%) patients developed shingles: 241 (0.34%) among the vaccinated and 2194
      (0.98%) among the unvaccinated. The VE for preventing shingles was 65.3% (95% CI:
      60.3-69.6%). The incidence rate in the vaccinated group was 2.95 (95% CI: 2.59
      3.34) vs 8.02 (95% CI: 7.68-8.36) per 1000 person years in the unvaccinated
      group. Risk of PHN was 0.02% and 0.06% in the respective vaccinated and
      unvaccinated groups. The VE for preventing PHN was 72% (95% CI: 50.0-83.9%). PHN
      incidence rates were 0.16 (95% CI: 0.08-0.27) and 0.53 (95% CI: 0.44-0.62) per
      1000 person years in the vaccinated and unvaccinated groups, respectively.
      CONCLUSIONS: ZVL reduced the risk of shingles among an elderly population. Given
      the negative impact of shingles and PHN on QoL, the benefits of vaccination are
      clear. Improving uptake in the UK is needed in this population.

PMID- 30195490
TI  - Intranasal vaccination with ebola virus GP amino acids 258-601 protects mice
      against lethal challenge.
AB  - Ebola virus (EBOV) disease (EVD) leads to lethal hemorrhagic fever with a case
      fatality rate as high as 90%, thus posing a serious global public health concern.
      However, while several vaccines based on the EBOV glycoprotein have been
      confirmed to be effective in animal experiments, no licensed vaccines or
      effective treatments have been approved since the first outbreak was reported in
      1976. In this study, we prepared the extracellular domain of the EBOV GP protein
      (designated as N20) by prokaryotic expression and purification via
      chromatography. Using CTA1-DD (designated as H45) as a mucosal adjuvant, we
      evaluated the immunogenicity of N20 by intranasal administration and the
      associated protective efficacy against mouse-adapted EBOV challenge in mice. We
      found that intranasal vaccination with H45-adjuvanted N20 could stimulate humoral
      immunity, as supported by GP-specific IgG titers; Th1 cellular immunity, based on
      IgG subclasses and IFN-gamma/IL-4 secreting cells; and mucosal immunity, based on
      the presence of anti-EBOV IgA in vaginal lavages. We also confirmed that the
      vaccine could completely protect mice against a lethal mouse-adapted EBOV (MA
      EBOV) challenge with few side effects (based on weight loss). In comparison, mice
      that received N20 or H45 alone succumbed to lethal MA-EBOV challenge. Therefore,
      mucosal vaccination with H45-adjuvanted N20 represents a potential vaccine
      candidate for the prevention of EBOV in an effective, safe, and convenient
      manner.

PMID- 30195491
TI  - MAL2 promotes proliferation, migration, and invasion through regulating
      epithelial-mesenchymal transition in breast cancer cell lines.
AB  - BACKGROUND: Breast cancer is one of the most common malignant tumors in women.
      However, the underlying molecular mechanisms of breast cancer are still far to
      clear. With the development of sequencing technology, we discovered that MAL2 is
      overexpressed in tumor tissues. But the major function of MAL2 in breast cancer
      has not to be well confirmed. MATERIALS AND METHODS: We downloaded and analyzed
      the MAL2 expression in The Cancer Genome Atlas (TCGA) database. Real-time
      quantitative polymerase chain reaction (RT-qPCR) was conducted to detect the
      expression of MAL2 in 35 breast cancer patients. Then, we performed
      proliferation, colony formation, migration, invasion and western blot assays to
      investigate the role of MAL2 in breast cancer cell lines (MDA-MB-231 and BT-549).
      RESULTS: In our research, we found that MAL2 is remarkably overexpressed in
      breast cancer tissues compared to adjacent non-cancer tissues by RT-qPCR (T: N =
      5.28 +/- 4.34:1.82 +/- 1.11, P < 0.001) and high expression of MAL2 has worse
      overall survival in TCGA cohort (P = 0.0032). Knocked down MAL2 could decrease
      the ability of proliferation, migration, and invasion of breast cancer cell
      lines. Our Western Blot assay results investigated that MAL2 could regulate EMT.
      CONCLUSION: In this study, we demonstrated the function of MAL2 in breast cancer
      cell lines and it might act as an oncogene in breast cancer.

PMID- 30195492
TI  - Presence of calpain-5 in mitochondria.
AB  - Calpains are Ca2+-dependent cysteine proteases that are widely distributed in
      animal tissues and modulate a variety of cellular processes. There are 15 members
      of the calpain family in mammals. In animal cells, there are three types of
      calpains, viz., calpain-1, calpain-2, and calpain-10 in the mitochondria. The
      three types of calpains have been shown to play significant roles in
      pathophysiological conditions, including in apoptosis- and necrosis-like cell
      death. One of the severe retinal diseases, autosomal dominant neovascular
      inflammatory vitreoretinopathy, is known to be induced by mutations of the
      calpain-5 gene. However, the distribution of calpain-5 in the retina has not been
      elucidated. Therefore, in the present study, we determined the localization of
      calpain-5 in the porcine retina. We detected calpain-5 in the inner segment of
      photoreceptor cells using immunohistochemistry. With immunoelectron microscopy,
      calpain-5 was localized in the mitochondria of photoreceptor cells. Western blot
      analyses showed that calpain-5 was present in each mitochondrial subfraction.
      Furthermore, we showed that the molecular weight of mitochondrial calpain-5 was
      slightly smaller than cytosolic one. Our results demonstrated that a novel
      mitochondrial calpian, calpain-5, was localized in the mitochondria of retinal
      photoreceptor cells.

PMID- 30195493
TI  - Activation of brown adipocytes by placental growth factor.
AB  - Gestational diabetes mellitus (GDM) is a type of diabetes and occurs during
      pregnancy. Brown adipose tissue (BAT) improves glucose homeostasis and mitigates
      insulin resistance, however, its activity is reduced in GDM. Placenta growth
      factor (PlGF) is an angiogenic factor produced by placental trophoblasts.
      Nevertheless, whether and how PlGF could affect BAT function in GDM are not
      defined. To investigate this question, 91 non-diabetic pregnant participants and
      73 GDM patients were recruited to Gynaecology and Obstetrics Centre in Lu He
      hospital. Serum levels of PlGF were quantified by ELISA. Skin temperature was
      measured by far infrared thermography in the supraclavicular region where
      classical BATs were located. The direct effect of PlGF on BAT function was
      explored using the established human preadipocyte differentiation system.
      Thereby, we demonstrated that serum levels of PlGF were lower in GDM patients
      compared with controls, which was accompanied by decreased skin temperature in
      the supraclavicular region. By qPCR and western blot, mRNA and protein expression
      of UCP1 and OXPHOS were elevated in differentiated adipocytes treated with PlGF.
      PlGF stimulated mitochondrion transcription and increased copy number of
      mitochondrial. When subjected for respirometry, PlGF-treated differentiated
      adipocytes showed higher oxygen consumption rates than controls. PlGF induced
      AMPK phosphorylation and blockade of AMPK phosphorylation blunted UCP1 and OXPHOS
      expression in differentiated adipocytes. PlGF administration reduced cholesterol
      and triglyceride content in the liver and improved insulin sensitivity in db mice
      compared with control. In Conclusion, PlGF could activate BAT function.
      Downregulation of PlGF might contribute to the reduced BAT activity in GDM.

PMID- 30195494
TI  - Corin is highly expressed in atherosclerosis models.
AB  - Corin is a serine protease mainly expressed in the heart, where it regulates
      blood pressure and cardiac function through activating pro-atrial natriuretic
      peptide (pro-ANP) to ANP. Its expression has also been detected in non-cardiac
      tissues. However, there is no report so far about the distribution and function
      of corin in aorta and in related diseases such as atherosclerosis. This study was
      the first to explore corin expression in aorta both under normal conditions and
      in atherosclerosis models. In vivo, we found corin had a basal level of
      expression in aortas, mainly in intimal endothelial cells and was significantly
      elevated in mouse atherosclerosis model. Moreover, we observed pro-ANP, the
      specific substrate of corin, was also expressed in mice aortas and increased in
      mouse atherosclerosis model. In vitro, we further demonstrated corin expression
      in cultured vascular endothelial cells and its induced expression after ox-LDL
      stimulation. Our results suggested that corin may play important roles in aorta
      physiology and in the pathophysiological process of atherosclerosis in an
      autocrine manner and has potential clinical value for the treatment of
      atherosclerosis.

PMID- 30195495
TI  - MicroRNA-98 regulates hepatic cholesterol metabolism via targeting sterol
      regulatory element-binding protein 2.
AB  - Hypercholesterolemia is an important risk factor for coronary heart disease.
      Although a lot of research has been conducted, the regulation of cholesterol
      metabolism is still largely unknown. Some miRNAs have been found to play critical
      role in the cholesterol metabolism. MiR-98 is a miRNA whose function has been
      reported mainly in tumorigenesis. In this study, we elucidate a novel role of miR
      98 in cholesterol metabolism. We found that the expression of miR-98 was
      decreased significantly in hypercholesterolemic patients compared with healthy
      control subjects. Furthermore, we identified that SREBP-2, an important
      transcriptional factor in cholesterol metabolism, was a direct target of miR-98.
      Overexpression of miR-98 significantly repressed the 3'-UTR reporter activities
      of SREBP-2 in a dose-dependent manner in HepG2 cells, while the effect of miR-98
      was blocked when the binding site of miR-98 within the SREBP-2 3'-UTR was
      mutated. And overexpression of miR-98 reduced both the mRNA and protein levels of
      HMGCR and LDLR significantly in vitro, which are two target genes of SREBP-2.
      Furthermore, MiR-98 overexpression reduced the intracellular total cholesterol
      levels dramatically. Moreover, we overexpressed the miR-98 by lentiviral tail
      vein injection in vivo. Compared with the control mice, the miR-98 overexpression
      mice showed lower serum cholesterol level and decreased SREBP-2, HMGCR as well as
      LDLR expression. Our data confirmed that reduced expression of miR-98 potentially
      contributes to disturbance of cholesterol metabolism. MiR-98 might be a novel
      therapeutic target to hypercholesterolemia.

PMID- 30195496
TI  - Activin A induces leiomyoma cell proliferation, extracellular matrix (ECM)
      accumulation and myofibroblastic transformation of myometrial cells via p38 MAPK.
AB  - OBJECTIVE: The objective of this study was to evaluate the role of Activin A and
      p38beta MAPK-activated signaling in human leiomyoma cells, myometrial cells and
      mouse myometrial tissues. METHODS: The immortalization human leiomyoma cells
      (HuLM), the immortalized human myometrial cells (HM) and mouse myometrial tissues
      were treated with Activin A (4 nM) and/or specific p38 inhibitor SB202190 (10
      MUM) for different days of interval (to measure proliferation rate) or 1 h (to
      measure signaling molecules) or 48 h (to measure proliferating markers Ki-67, ECM
      mRNA, and/or ECM protein expression) by real-time PCR, Western blot, and/or
      immunocytochemistry. RESULTS: Activin A induced cell proliferation and ECM
      proteins accumulation in HuLM cells via p38 MAPK. Activin A also induced
      myofibroblastic transformation in HM cells and mouse myometrical tissues via the
      phosphorylation of p38. The effects of Activin A in leiomyoma cells, myometrical
      cells and tissues were abolished by p38alpha/beta MAPK inhibitor SB202190.
      CONCLUSION: This study demonstrates Activin A-p38 MAPK signaling pathway in
      leiomyoma and myometrium may contribute to excessive ECM production, leiomyoma
      growth and progression. Targeting Activin A-p38 MAPK signaling pathway could be a
      potential therapeutic intervention for uterine leiomyoma.

PMID- 30195497
TI  - Activation of neuregulin-4 in adipocytes improves metabolic health by enhancing
      adipose tissue angiogenesis.
AB  - Obesity often causes systemic metabolic disorders in close association with
      adipose tissue dysfunction. Adipose tissue contains well-developed vasculatures,
      and obesity mediates vascular rarefaction that causes hypoxia and triggers
      inflammation in adipose tissue. Adipose tissue-derived neuregulin-4 (Nrg4) is an
      immerging factor that is critically involved in metabolic homeostasis. We
      recently identified that Nrg4 is an angiogenic adipokine that plays an important
      role in maintaining adipose tissue vasculature. Here, we further validated its
      beneficial role in metabolic health primarily by enhancing adipose tissue
      angiogenesis. Targeted activation of Nrg4 in adipocytes improved metabolic health
      in mice under both normal and high fat dietary condition without changes in body
      weight. Activation of Nrg4 increased blood vessels in white adipose tissue, and
      ameliorated adipose tissue hypoxia under obese condition. Of note, inhibition of
      angiogenesis by sugen-treatment abolished the beneficial effects of Nrg4 on
      systemic metabolic health. Furthermore, targeted inhibition of Nrg4-ErbB
      signaling in adipose tissue vasculature using prohibitin binding peptide
      conjugated nanocarrier abrogated the enhanced adipose tissue angiogenesis, and
      canceled the improved metabolic health induced by Nrg4 activation. These data
      further support a crucial role of Nrg4 in maintaining systemic metabolic
      homeostasis at least partially through enhancing adipose tissue angiogenesis.

PMID- 30195498
TI  - Inhibition of liver mitochondrial membrane permeability transition pore opening
      by quercetin and vitamin E in streptozotocin-induced diabetic rats.
AB  - Diabetes mellitus is a chronic metabolic disorder characterized by rise in blood
      glucose levels and generation of free radicals which could induce mitochondrial
      membrane permeability transition (MMPT) pore opening. This study examined the in
      vivo action of quercetin and vitamin E on MMPT in the liver of streptozotocin
      induced diabetic rats orally pre-treated with 30 mg quercetin/kg body weight
      (STZQ), 10 mg vitamin E/kg body weight (STZVit.E) and 0.6 mg glibenclamide/kg
      body weight (STZG). Male albino wistar rats were used in the study and were
      injected intraperitonially with streptozotocin (STZ) (45 mg/kg body weight) in
      citrate buffer. The degrees of serum and tissue peroxidation, alanine and
      aspartate aminotransferase activity were investigated. MMPT pore was assessed as
      mitochondrial swelling and was monitored spectrophotometrically as changes in
      absorbance at 540 nm under succinate-energized condition. There was significant
      increase in serum glucose level, degree of tissue peroxidation, alanine and
      aspartate aminotransferase activity, cholesterol and triglycerides values in the
      diabetic control rats following streptozotocin induction. All the treatment had
      effect on the damage caused by streptozotocin. Quercetin exhibited the highest
      chemopreventive activity. Quercetin and vitamin E significantly reduced the blood
      glucose level, degree of tissue peroxidation and alanine and aspartate amino
      transferase activity. In vivo rat liver MMPT pore was opened in diabetic control
      rats and significantly inhibited in STZQ, STZV and STZG treated groups by 72.3%,
      58.5% and 87.5% respectively. The activity of quercetin and vitamin E were
      substantiated by histopathological evaluation. Our study suggests that quercetin
      is an effective therapeutic agent for preventing hepatic tissues from oxidative
      stress resulting from streptozotocin-induced diabetes by inhibiting apoptotic
      processes in their target cells.

PMID- 30195499
TI  - Silymarin amplifies apoptosis in ectopic endometrial tissue in rats with
      endometriosis; implication on growth factor GDNF, ERK1/2 and Bcl-6b expression.
AB  - The present prospective study was done to evaluate the effect of silymarin (SMN)
      on endometriotic-like legions establishment and growth in experimentally-induced
      endometriosis. For this purpose, the experimental endometriosis was induced in 12
      rats and then the animals subdivided into endometriosis-sole and SMN (50 mg kg-1,
      orally)+endometriosis groups. Following 28 days, the legions establishment, size,
      Glial cell line-derived neurotrophic factor (GDNF), gfralpha1, B Cell Lymphoma 6
      (Bcl-6b), Bcl-2, extracellular regulator kinase (ERK1/2) expression ratios,
      angiogenesis, the apoptosis and fibrosis indices were investigated. The SMN
      significantly (P < 0.05) decreased the enometriotic-like legions establishment
      and size, decreased mRNA levels of GDNF, gfralpha1, Bcl-6b and Bcl-2 and
      remarkably diminished GDNF, gfralpha1, Bcl-6b and Bcl-2-positive cells
      distribution/mm2 of tissue versus endometriosis-sole group. The SMN +
      endometriosis group exhibited a significant (P < 0.05) enhancement in ERK1/2
      expression and represented diminished vascularized area and increased apoptosis
      and fibrosis indices, as well. In conclusion, the SMN by down-regulating GDNF and
      its receptor gfralpha1 expression inhibits GDNF-gfralpha1 complex generation and
      consequently suppresses Bcl-6b expression. Moreover, the SMN by enhancing the
      ERK1/2 expression and by suppressing the Bcl-2 expression promotes the apoptosis
      pathway. Finally, the SMN by down-regulating the angiogenesis ratio accelerates
      apoptosis and consequently induces severe fibrosis in endometriotic-like legions.

PMID- 30195500
TI  - The morphological and functional significance of the NOS/NO system in the
      respiratory, osmoregulatory, and contractile organs of the African lungfish.
AB  - This review aims to summarize the changes of the NOS/NO system which occur in the
      lungs, gills, kidney, heart, and myotomal muscle of air breathing fish of the
      genus Protopterus, i.e. P. dolloi and P. annectens, in relation to the switch
      from freshwater to aestivation, and vice-versa. The modifications of NOS and its
      partners Akt and Hsp-90, and HIF-1alpha, detected by immunohistochemical and
      molecular biology methods, are discussed together with the apoptosis rate,
      evaluated by TUNEL. We hypothesize that these molecular components are key
      elements of the stress-induced signal transduction/integration networks which
      allow the lungfish to overcome the dramatic environmental challenges experienced
      at the beginning, during, and at the end of the dry season.

PMID- 30195501
TI  - Functional morphology of the respiratory organs of the air-breathing fish with
      particular emphasis on the African catfishes, Clarias mossambicus and C.
      gariepinus.
AB  - The evolution of air-breathing and transition from water to land were pivotal
      events that greatly determined the ecological diversification, the advances and
      the successes of animal life. During their relocation onto land, the so-called
      bimodal breathers were literally caught at the water-air interface. Among such
      animals are the diverse air-breathing bony fish. Such taxa, however, strictly do
      not constitute the so-called 'bridging animals', i.e., the inaugural animals that
      crossed from water to land, nor are they their direct progenitors. The pioneer
      transitional animals were the Devonian rhipidistian amphibians that possessed a
      primitive lung which acquired O2 directly from air and discharged CO2 back into
      the same. By having particular morphological and physiological adaptations for
      terrestrialness, the modern amphibious- and aquatic air-breathers are heuristic
      analogues of how and why animals relocated from water to land. It has generally
      been espoused that lack or dearth of O2 in water, especially in the warm tropical
      one, was an elemental driver for adoption of air-breathing. There is, however, no
      direct causal relationship between the evolution of air-breathing and the shift
      onto land: the move onto land was a direct solution to the existing inimical
      respiratory conditions in water. This is evinced in the facts that: a) even after
      attaining capacity of air-breathing, an important preadaptation for life on land,
      some animals continued living in water while periodically accessing air, b) in
      the fish species that live in the well-oxygenated waters, e.g., torrential
      rivers, only few air-breathe and c) air-breathing has still evolved in
      freshwaters and seawaters, where levels of dissolved O2 are sufficiently high.
      Here, the structure and function of the respiratory organs of the air-breathing
      fish are succinctly outlined. Two African catfishes, Clarias mossambicus and C.
      gariepinus are highlighted.

PMID- 30195502
TI  - Changes in bovine milk fat globule membrane proteins caused by heat procedures
      using a label-free proteomic approach.
AB  - The milk fat globule membrane (MFGM) plays an important role in stabilizing fat
      in the aqueous phase, and the components of this membrane are involved in
      multiple biological functions. Here, we investigated changes in the protein
      composition of the MFGM fraction between raw and heated whole milk using a label
      free proteomic approach. In total, 612 MFGM-related proteins were identified in
      all groups. Compared with raw milk, the number of proteins that were not
      identified in the MFGM fraction was increased from pasteurized milk to ultra-high
      temperature milk, whereas the number of milk proteins incorporated into the MFGM
      fraction was similar among heated groups. The abundances of several milk proteins
      (beta-lactoglobulin and beta-casein) were increased in the heated milk groups in
      a temperature-dependent manner. From our functional analysis, proteins that were
      not identified in the MFGM fraction of heated milk were mainly associated with
      multiple biological functions. These findings provided novel insights into the
      effects of heat procedures on MFGM protein components and their potential
      physiological functions, thereby yielding data on the appropriate heating
      procedures to use for raw milk.

PMID- 30195503
TI  - Sensory evaluation of the synergism among ester odorants in light aroma-type
      liquor by odor threshold, aroma intensity and flash GC electronic nose.
AB  - Although esters were important odorants in light aroma-type liquor, it was still
      puzzling that sensory interaction between esters made the odor quality of light
      aroma-type liquor outstanding. The aim of the paper was to investigate perceptual
      interaction among esters. The odor thresholds of eighteen esters and 35 binary
      mixture were determined by a three-alternative forced-choice procedure. The
      relationship between odor threshold and carbon chain length of homologous ethyl
      esters was investigated. Moreover, 31 binary mixtures present either a
      synergistic effect or additive action. Furthermore, odor quality and odor
      intensity were determined by p/tau plot and sigma/tau plot, respectively. From
      the p/tau plot, an ideal sigmoidal function for odor quality was obtained. From
      the sigma/tau plot, for all 120 binary mixtures, just 9 mixtures were in the
      hyper-additivity area (sigma > 1.05), and two were in the so-called perfect
      additivity area (0.95 < sigma < 1.05). Almost one half (48%) showed compromise
      level. Finally, a significantly difference was observed by flash gas
      chromatography electronic nose (p < .05). Sensory analysis revealed that a mask
      effect of fruity note was occurred by adding ethyl phenylacetate at various
      levels (100, 2500, 58,000 ppb) to the fruit recombination and an enhancement
      effect of floral note was reported by adding phenylethyl acetate at low (1400
      ppb) or high level (11,500 ppb). It was noticed that sweet note was significantly
      enhanced by adding phenylethyl acetate at peri-threshold (3200 ppb).

PMID- 30195504
TI  - Sephadex LH-20 fractionation and bioactivities of phenolic compounds from
      extracts of Finnish berry plants.
AB  - In order to assist developing a natural, safe food-preservative, aqueous
      ethanolic extracts of leaves and berries of eight Finnish berry plants were
      fractionated with Sephadex LH-20 column chromatography. For each fraction,
      phenolic compounds were analyzed with NMR, UPLC-DAD-ESI-MS and HPLC-DAD. The
      antioxidant activities of the fractions were investigated using oxygen radical
      absorbance capacity (ORAC) assay, and the antibacterial activities were evaluated
      against foodborne pathogens Staphylococcus aureus and Escherichia coli.
      Antioxidant activities of the fractions correlated highly with both the total
      concentration and structural feature of phenolic compounds, including both
      flavonoids and non-flavonoid phenolics. ORAC value correlated strongly with the
      concentration of (+)-catechin, (-)-epicatecin, quercetin glycosides, and
      anthocyanins. Increase in size and number of sugar moieties may reduce the
      antioxidative activities of quercetin glycosides. Type of sugar moieties may have
      a significant role in influencing peroxyl-radicals scavenging ability of
      quercetin glycosides with monosaccharides as a single sugar moieties. Most of the
      fractions inhibited the target microbes. S. aureus strains expressed a higher
      sensitivity to phenolic compounds than E. coli strains.

PMID- 30195505
TI  - NMR metabolomic fingerprinting distinguishes milk from different farms.
AB  - A fast and reproducible protocol for milk Nuclear Magnetic Resonance (NMR)
      metabolomic fingerprinting was developed, allowing for an accurate discrimination
      among milk samples from large-scale distribution, as well as among milk sample
      from different farms located in the same restricted geographical area. Seasonal
      variations in milk composition and correlations with cows' nutritional patterns
      are also assessed, underlining relationships between feeding and metabolites. The
      most important difference was related to the use of silage feeding. This finding
      is relevant to assess the suitability of milk for different dairy products. A
      prominent example is parmesan cheese, the preparation protocol of which excludes
      milk from silage-fed cows.

PMID- 30195506
TI  - 1H NMR and multivariate data analysis of the differences of metabolites in five
      types of dry-cured hams.
AB  - In order to distinguish the taste styles of dry-cured hams (Jinhua, Xuanwei,
      Country, Parma and Bama), we established a 1H nuclear magnetic resonance
      spectroscopy method to identify metabolites. Totally, 33 charged metabolites,
      including amino acids, organic acids, nucleic acids and their derivatives,
      sugars, alkaloids and others were identified. The abundant glutamate, lysine,
      alanine, leucine and lactate could be the major contributors of taste. Total
      variables were explained by PC1 (67.7%) and PC2 (16.0%) which showed that Parma
      and Xuanwei styles were close to each other (similar amino acids, peptide,
      organic acids and alkaloids contents). Bama style showed the highest PC1 and
      amino acids, organic acids and alkaloids contents. Country style was located on
      the left-most area of PC1 (the lowest amino acids, organic acids and peptide, but
      the highest sugars contents). Sensory evaluation revealed that Bama ham had the
      highest overall taste score, followed by Jinhua, Parma, Xuanwei and American
      Country ham. We concluded that the proportions and combinations of taste
      components explained the specific taste instead of any single component. These
      findings provided a better understanding of different metabolomics among hams.

PMID- 30195507
TI  - Modulation of physical properties of microfluidized whey protein fibrils with
      chitosan.
AB  - There is an increasing market for food and beverage products enriched in proteins
      and dietary fibers due to their potential health benefits. In this study, the
      effect of heating (85  degrees C, 20 min), microfluidization (20,000 psi), and pH
      (2 to 6.5) on the physicochemical properties of aqueous solutions containing
      mixtures of whey protein fibrils (7.5%; WPF) and chitosan (0.5%; CN) were
      examined. Heating of the mixed systems increased their turbidity and apparent
      viscosity, which was attributed to the formation of protein-rich particles.
      Interestingly, heating the mixed systems and then applying microfluidization led
      to phase separation and a lower apparent viscosity, which was attributed to high
      pressure disruption of the whey protein fibrils. The pH of the systems
      significantly influenced their appearance, turbidity, particle size, and apparent
      viscosity, with high turbidity and viscosity, and large particle size occurring
      from pH 3.5 to 5.5. These effects were attributed to protein aggregation close to
      its isoelectric point (pH 5) coupled with electrostatic attraction between
      anionic groups on the whey protein and cationic groups on the chitosan. The
      addition of chitosan increased the net isoelectric point from pH 5 for pure whey
      protein to pH 6 for the mixed system. Overall, this study showed that the
      appearance and rheological properties of protein-dietary fiber mixtures could be
      manipulated by heating, microfluidization, and pH adjustment. This information
      may be useful for designing protein and fiber enriched food and beverage products
      with desirable physical and sensory properties.

PMID- 30195508
TI  - Essential oils as natural additives to prevent oxidation reactions in meat and
      meat products: A review.
AB  - Oxidation reactions during manufacturing, distribution, and storage of meat and
      meat products result in undesirable physicochemical changes and aromas, which
      leads to detrimental effects on the product quality. This could be translated
      into the consumer dissatisfaction and economic loss. One of the most common
      practices to overcome this issue is the incorporation of synthetic antioxidants.
      However, the increasing health-consciousness of consumers and their preference
      for natural additives leads to the search of natural alternatives to synthetic
      antioxidants. A number of essential oils have strong antioxidant properties and
      are explored as potential alternatives to chemical antioxidants in the meat
      industry. These compounds are classified as Generally Recognized as Safe (GRAS),
      and their application single or combined with other essential oils, ingredients
      or preservation technologies have beneficial effects on meat products. Their
      activity depends on several parameters including their concentrations, their
      possible synergistic effects, and the extraction method used to obtain them.
      Although steam distillation is the most common industrial technique for essential
      oils extraction, novel technologies have been emerged to address the drawbacks of
      the traditional extraction method and to obtain high-quality essential oils. This
      paper provides an overview of the application of essential oils as potential
      substitutes for synthetic antioxidants in the meat industry, exploring their
      mechanism of action against oxidation reactions, and the effect of extraction
      methods on their effectiveness.

PMID- 30195509
TI  - Physico-chemical and structural properties of crystalline inulin explain the
      stability of Lactobacillus plantarum during spray-drying and storage.
AB  - The stabilizing capacity of crystalline inulin during spray-drying and storage of
      Lactobacillus plantarum CIDCA 83114 was assessed. In a first step, the physical
      properties of the matrices were investigated, using amorphous inulin as control.
      Melting and glass transition temperatures, water sorption isotherms, water
      activity, and infrared spectra were determined. Microorganisms were spray-dried
      at a pilot scale in both amorphous and crystalline matrices. After that, scanning
      electronic and confocal microsopies provided a full landscape about the
      interactions between microorganisms and crystals, and also the bacterial location
      within the amorphous matrices. The technological properties of the dehydrated
      microorganisms (culturability and acidification capacity) during storage at
      different water activities were also evaluated. Both amorphous and crystalline
      inulins were adequate matrices to stabilize microorganisms. However, crystalline
      inulin was more stable than amorphous one, especially when the storage
      temperature was close to the glass transition temperature, resulting in a better
      matrix to protect microorganisms during pilot spray-drying and storage.
      Furthermore, no accumulation of insoluble inulin was observed after resuspending
      the dehydrated microorganisms in crystalline inulin matrices, which appears as a
      clear technological advantage with regard to the amorphous one. Considering the
      prebiotic character of inulin and the probiotic properties of L. plantarum CIDCA
      83114, this work developed an integrated approach, both from a fundamental and
      from an applied viewpoint, supporting the incorporation of such ingredients in
      the formulation of food products.

PMID- 30195510
TI  - To what extent does the nitrosation of meat proteins influence their
      digestibility?
AB  - Nitrosation can occur during meat digestion due to the physicochemical conditions
      of the stomach (low pH and reducing conditions). The aim of the present study was
      to elucidate the link between the nitrosation of proteins from beef meat and
      their digestibility by comparing cooked meat digested with and without the
      addition of nitrite. To do this, a dynamic in vitro artificial digestive computer
      controlled system (DIDGI(r)) was used to reflect human gastro-intestinal
      conditions. Peptides and proteins from gastrointestinal digestion were identified
      by high-resolution LC-MS/MS mass spectrometry. The results showed a dynamic
      digestion pattern of meat proteins according to their cellular localization. A
      combined effect of the digestive compartment and the addition of nitrite was
      established for the first time on peptides profile, linking the nitrosation of
      proteins and their digestibility.

PMID- 30195511
TI  - Growth-inhibitory activity of phenolic compounds applied in an emulsifiable
      concentrate - ferulic acid as a natural pesticide against Botrytis cinerea.
AB  - Phenolic compounds are part of the protection system of plants against all kinds
      of pests and are therefore considered a natural alternative to conventional plant
      protection agents. Five phenolic compounds (phlorizin, resveratrol, ferulic acid,
      5-n-alkylresorcinols, and quercetin) were used as active ingredients in the
      preparation of a bioactive emulsion and screened for their ability to inhibit the
      growth of four phytopathogenic fungi - Aspergillus niger, Botrytis cinerea,
      Penicillium expansum, and Fusarium culmorum. By using design of experiments,
      several interactions between the phenols were determined, however, ferulic acid
      was identified as highly effective against the growth of Botrytis cinerea. The
      growth-inhibitory effect of this emulsion was enhanced by adapting the ferulic
      acid concentration (0.085%, m/v) with the help of response surface methodology.
      Subsequent tests confirmed the activity against the growth of nine fungicide
      resistant Botrytis cinerea isolates and showed promising results against the
      infection of injured and contaminated grapes.

PMID- 30195512
TI  - Role of prebiotics in regulation of microbiota and prevention of obesity.
AB  - There is an increasing incidence in non-communicable diseases (NCD) such as
      obesity, diabetes and metabolic syndrome all over the world, despite of the
      governmental investments in healthy policies. Some of these diseases represent a
      high economic burden to individuals and society, demanding urgency in the
      identification of risk factors and appropriate solutions. Inadequate nutrition
      habits are an important risk factor for developing these diseases, and the
      consumption of functional foods such as prebiotics, probiotics, and phenolic
      compounds may contribute to mitigate them. It has been reported that the
      consumption of prebiotics can cause positive changes in the intestinal
      microbiota. The healthy microbiota, consisting mainly of Bifidobacterium and
      Lactobacillus, ferment prebiotics producing compounds that appear to play a
      protective role against metabolic diseases. Despite the growing number of
      publications on the effects of regular consumption of prebiotics in experimental
      models, additional studies on their effects on humans are needed to bring more
      subsidies to public health programs. This manuscript aims to review the
      literature on the possible benefits of ingestion of prebiotics in the control of
      obesity.

PMID- 30195513
TI  - Glycation of fish protein impacts its fermentation metabolites and gut microbiota
      during in vitro human colonic fermentation.
AB  - The aim of this study was to investigate the fermentation properties of fish
      protein (FP) glycated with glucose at two different heating time (24 h and 48 h,
      50  degrees C, GFP24 and GFP48), using an in vitro batch fermentation model of
      human distal colon. The heated fish protein in absent of glucose was also as
      controls. The lower glycation extent of fish protein, with a lower browning
      intensity and bound sugar, enhanced the production of acetate and propionate. The
      formation of indole and ammonia was inhibited by the glycation of fish protein,
      but less affected by its glycation extent. Compared to FP, the glycation of fish
      protein significantly increased (p < .05) the relative abundance of genera
      Lactococcus for GFP24 (47%) and GFP48 (71%), whereas decreased dominant genera
      Bacteroides for GFP24 (32%) and GFP48 (23%). Compared to GFP24, GFP48 indicated
      significantly higher relative abundance of Holdemania, Streptococcus,
      Enterococcus and Lactobacillus, and lower amounts of Parabacteroides (p < .05).
      In the meantime, the heated treatments in the absent of glucose resulted in the
      increase of some genera Dialister, Arobacter, Clostridium_sensu_stricto_1,
      Phascolarctobacterium and Veillonella, and also ammonia production. Furthermore,
      the correlation analysis confirmed that the glycation of fish protein for the
      decrease of ammonia and indole production was associated with the changes of some
      proteolytic bacteria genera, including Bacteroides, Dialister and
      Parabacteroides. Thus, the glycated fish protein rich in Amadori products greatly
      change the profiles of fermentation metabolite and gut microbiota, and these
      changes can have a potential impact on host health.

PMID- 30195515
TI  - Dry heating of whey proteins leads to formation of microspheres with useful
      functional properties.
AB  - Modification of whey protein isolate (WPI) powders is used in the food industry
      to enhance the functional properties of WPI. We investigated the impact of severe
      dry heating (DH) at 100  degrees C for up to 36 h on an alkaline-treated (pH
      9.5), spray dried (water activity of ~0.24) WPI powder. Dry heated powders and
      their reconstituted suspensions were analysed. DH for 0-6 h led to 47% loss of
      native proteins, increases in the levels of soluble aggregates (*2.2) and of
      advanced glycation end-products of the Maillard reaction (at least *2.7) and to
      powder browning (at least *3) with a 95% decrease in free lactose content. DH for
      at least 12 h led to a decrease in soluble aggregates with concomitant formation
      of large, stable and insoluble microparticles. These microparticles had a
      microsphere structure, contained 98% of water phase and were made of insoluble
      powder particles resulting from protein cross-links during DH. Microparticle size
      could be altered by varying the pH of the suspension: at pH 6.5, microsphere size
      was 3-5 times larger than powder particle size, but decreased as the suspension
      pH neared the isoelectric point. DH could be a useful method for producing
      functional protein ingredients as these microparticles had very high water
      retention properties and high viscosity values.

PMID- 30195514
TI  - Recovery of bioactive anthocyanin pigments from Ficus carica L. peel by heat,
      microwave, and ultrasound based extraction techniques.
AB  - Due to its coloration, the fig (Ficus carica L.) peel, a by-product of fruit
      processing and/or consumption, is a potential source of anthocyanin compounds. In
      the present study different extraction techniques (heat, ultrasound, and
      microwave) were compared aiming to recover the anthocyanin pigments and optimize
      its extraction conditions. A response surface methodology tool with three factors
      and five levels for each factor was used according to a circumscribed central
      composite design. The variables tested for the heat and microwave extraction
      methods were time, temperature, and solvent proportion (ethanol/water ratio),
      meanwhile, for the ultrasound method, the variables tested were the ultrasonic
      power, time, and solvent proportion. The anthocyanin composition of the extract
      was determined by HPLC-DAD-ESI/MS, and the used criteria responses were: i)
      quantification of cyanidin 3-rutinoside (C) in the extracted residue (mg C/g R)
      and in the dried peel (mg C/g P dw), and the extraction yield of the obtained
      residue (g R/g P dw). Ultrasound extraction was the most effective method,
      yielding 3.82 mg C/g R at the optimal global extraction conditions (21 min, 310
      W, and 100% of ethanol). Additionally, the solid-to-liquid ratio effect was
      studied at the optimal conditions, using a dose-response format, in view of its
      plausible transference to industrial level. For the ultrasound method, an
      increased non-linear relationship was observed for concentrations in the range 5
      to 200 g/L, being the optimal solution close to 150 g/L. In brief, the obtained
      results show the potential of fig peels as a source of anthocyanin pigments, with
      potential uses in various industrial fields, such as food, pharmaceutical, and
      cosmetic.

PMID- 30195516
TI  - Phenolic acids profile, nutritional and phytochemical compounds, antioxidant
      properties in colored barley grown in southern Italy.
AB  - Free, soluble conjugated, and insoluble bound phenolic acids and some of the main
      antioxidant phytochemicals (i.e., total polyphenols, proanthocyanidins,
      carotenoids) were investigated in 20 genotypes of colored barley. These included
      16F8 recombinant inbred lines (RILs) obtained from crosses of four parental
      lines: '2005 FG', 'K4-31, 'L94', and 'Priora'. The aim of this work was these to
      promote the introduction of new barley genotypes with high contents of such
      natural antioxidants, and of dietary fiber. These new genotypes will enlarge the
      market of novel functional foods. Large variations were seen in the contents of
      phytochemicals and beta-glucans across these barley genotypes. The highest
      protein (14.4%) and beta-glucan (4.6%) contents were in the blue naked parental
      genotype '2005 FG'. Overall, insoluble bound phenolic acids represented 88.3% of
      the total phenolic acids, and ferulic acid was the main conjugated phenolic acid.
      Salicylic and gallic acids were the most represented among the free phenolic
      acids, with no p-coumaric and cinnamic acids detected. Total polyphenols and
      proanthocyanidins were highest in the RILs '3009' (2917 MUg g-1) and '1997' (1630
      MUg g-1). The barley line with high total polyphenols (RIL '3009') also showed
      the highest antioxidant capacities (by both DPPH and ABTS methods: 13.4 MUmol g-1
      and 15.6 MUmol g-1, respectively). Among the RILs examined, '3004', '3008', and
      '3009' showed 30% higher antioxidant capacities than their parentals, thus
      providing potential health-promoting benefits.

PMID- 30195517
TI  - The effect on bioactive components and characteristics of chocolate by
      functionalization with raw cocoa beans.
AB  - Chocolate manufacturers often develop their own original blends of cocoa beans,
      which, after processing, will give an unique sensory properties to their
      chocolates. In recent years, there has been a trend in the production of an
      increasing amount of low-processed or unprocessed food. Therefore, we carried out
      the research in which we obtained and analyzed chocolates with different blends
      of cocoa liquors prepared from roasted and unroasted cocoa beans of Criollo and
      Forastero varieties.Studies have shown that viscosity and yield value increased
      and hardness of chocolates lowered with the increase content of cocoa liquor from
      unroasted beans. Chocolates with cocoa liquor from roasted beans were
      characterized by the largest ability to scavenge DPPH radicals. Antioxidant
      activity determined by the ORAC-FL method increased with increasing polyphenol
      content in the chocolates. Type of the cocoa liquor used induced minor changes in
      the polyphenol and fatty acid composition. Asparagine was determined at the
      highest concentration, followed by alanine, glutamine, and serine. The
      concentration of acetic acid was the higher the higher the content of unroasted
      beans. The increased content of cocoa liquor from unroasted beans caused the
      color of the chocolate to brighten, more red and yellow. All tested chocolates
      were characterized by good organoleptic properties and microbial stability.

PMID- 30195518
TI  - Preparation and modification of high dietary fiber flour: A review.
AB  - Dietary fiber, consisting of soluble dietary fiber and insoluble dietary fiber,
      has beneficial functional effects on the human body that are receiving
      increasingly attention. Refined flour lacks dietary fiber and poses potential
      risks to human health. Therefore, improving the nutritional value and processing
      performance of flour in the preparation and modification of high dietary fiber
      flour is of great importance. Whole-wheat flour, a high dietary fiber flour
      obtained by crushing whole-wheat grains, is rich in nutritional value. High
      dietary fiber flour obtained by adding bran back into the flour makes full use of
      the bran, which increases the utilization of wheat-milling byproducts. The
      addition of dietary fiber to flour is a direct method for obtaining high dietary
      fiber flour, and which has evolved with the development of the dietary fiber
      extraction industry. Further modifications of whole-wheat flour, bran, and
      dietary fiber, such as milling, extrusion, heat treatment, and biological
      treatment, can diminish the effect that bran materials on the quality of flour
      and flour products. This review summarizes methods used for the preparation and
      modification of three kinds of high dietary fiber flour and the effects of these
      different methods on the quality of flour and flour products, with the aim to
      provide guidance for the industrial preparation of high dietary fiber flour.

PMID- 30195519
TI  - Extraction of bioactive compounds and essential oils from mediterranean herbs by
      conventional and green innovative techniques: A review.
AB  - Market interest in aromatic plants from the Mediterranean is continuously growing
      mainly due to their medicinal and bioactive compounds (BACs) with other valuable
      constituents from essential oils (EOs). From ancient times, these plants have
      been important condiments for traditional Mediterranean cuisine and remedies in
      folk medicine. Nowadays, they are considered as important factors for food
      quality and safety, due to prevention of various deteriorative factors like
      oxidations and microbial spoilage. EOs have different therapeutic benefits (e.g.
      antioxidant, anti-inflammatory, antimicrobial, and antifungal), while BACs mostly
      affect nutritive, chemical, microbiological, and sensory quality of foods.
      Currently, many plant extracts are used for functional (healthy) foods, which
      additionally fuels consumer and industrial interest in sustainable and non-toxic
      routes for their production. EO yields from dried plants are below 5%. Their
      extraction is strongly dependent on the hydrophobic or lipophilic character of
      target molecules, hence the common use of organic solvents. Similarly, BACs
      encompass a wide range of substances with varying structures as reflected by
      their different physical/chemical qualities. Thus, there is a need to identify
      optimal non-toxic extraction method(s) for isolation/separation of EO/BCs from
      plants. Various innovative non-thermal extractions (e.g. ultrasound-, high
      pressure-, pulsed electric fields assisted extraction, etc.) have been proposed
      to overcome the above mentioned limitations. These techniques are "green" in
      concept, as they are shorter, avoid toxic chemicals, and are able to improve
      extract yields and quality with reduced consumption of energy and solvents. This
      research provides an overview of such extractions of both BAC and EOs from
      Mediterranean herbs, sustained by innovative and non-conventional energy sources.

PMID- 30195520
TI  - Preparation and characterization of inclusion complex of (+)-catechin with beta
      cyclodextrin.

PMID- 30195521
TI  - Immunomodulatory activity of non starch polysaccharides isolated from green gram
      (Vigna radiata).
AB  - Green gram, rich in dietary fiber is known to enhance the function of immune
      system. However information pertaining to the immunomodulatory potential of its
      non starch polysaccharides (NSPs) is scanty. Hence, five different NSPs were
      extracted successively using water (WSP), hot water (55 o C, HWSP), EDTA (0.5%,
      Pectins) and alkali (10%, Hemicellulose A and B) which varied in their arabinose
      to galactose ratio, sugar, protein, uronic acid contents, molecular weight
      distribution and immunomodulatory activity. Hemicellulose B was relatively rich
      in carbohydrate content (~95%) and also possessed potent immunomodulatory
      activity among the various NSPs. Hemicellulose B was further fractionated on DEAE
      cellulose column into six different fractions by eluting step-wise with water,
      ammonium carbonate (0.1, 0.2, 0.3 M AC) and sodium hydroxide (0.1 and 0.2 M
      NaOH). 0.1 M AC eluted fraction was found to be the major one amounting to ~ 50%
      yield and showed relatively significant (p < 0.001) activity towards splenocyte
      proliferation and macrophage activation as compared with rest of the DEAE eluted
      fractions.

PMID- 30195522
TI  - The effects of grape and red wine polyphenols on gut microbiota - A systematic
      review.
AB  - There is a growing body of evidence implicating the gut 'microbiome' role in
      overall human health. Bacterial species belonging to the genera Lactobacillus and
      Bifidobacterium are generally considered to be beneficial and are commonly used
      in probiotic applications, whereas increases in some genera including Clostridum,
      Eubacterium and Bacteroides are implicated in negative health outcomes. Dietary
      polyphenols are bioactive compounds that have been found to increase the numbers
      of beneficial bacteria and antimicrobial actions against pathogenic bacteria,
      however most studies have been conducted in animal models or in-vitro colonic
      models. The aim of this systematic review was to provide an overview of recent
      trials on the effect of dietary grape and red wine polyphenols on the gut
      microbiota in humans. Following PRISMA guidelines, a systematic review was
      conducted of electronic databases (PubMed, CINAHL, Cochrane Library, Wed of
      Science and Scopus) to identify human intervention trials examining the effect of
      grape or wine polyphenols on gut microbiota. Seven trials met the inclusion
      criteria. One study looked at changes in gut microbiota following the ingestion
      of de-alcoholised red wine or red wine, and six studies referred to gut
      microbiota as intermediates in formation of phenolic metabolites. All studies
      confirmed that ingested polyphenols from grape and red wine, were modulated by
      gut microbiota, increasing numbers of polyphenolic metabolites which were found
      in blood, urine, ileal fluid and faeces. Intake of polyphenols derived from grape
      and red wine can modulate gut microbiota and contribute to beneficial microbial
      ecology that can enhance human health benefits. Additionally, grape and red wine
      polyphenols were modulated by the gut microbiota and there is a potential for a
      two-way relationship between the gut microbiota and polyphenolic compounds.
      Nevertheless, additional research is required to fully understand the complex
      relationship between gut microbiota and dietary polyphenols before any health
      claims can be made in relation to human health.

PMID- 30195523
TI  - Microwave assisted extraction of phenolic compounds from four economic brown
      macroalgae species and evaluation of their antioxidant activities and inhibitory
      effects on alpha-amylase, alpha-glucosidase, pancreatic lipase and tyrosinase.
AB  - Four economically important brown algae species (Ascophyllum nodosum, Laminaria
      japonica, Lessonia trabeculate and Lessonia nigrecens) were investigated for
      phenolic compound extraction and evaluated for their antioxidant, anti
      hyperglycemic, and pancreatic lipase and tyrosinase inhibition activities.
      Microwave assisted extraction (MAE) at 110  degrees C for 15 min resulted in both
      higher crude yield and higher total phenolic content (TPC) for all algae species
      compared with those obtained by conventional extraction at room temperature for 4
      h, and Ascophyllum nodosum yielded the highest TPC. Antioxidant tests indicated
      that extracts acquired by MAE from four species all exhibited higher DPPH, ABTS
      free radical scavenging ability and reducing power than the conventional method.
      The extract of Lessonia trabeculate exhibited good alpha-amylase, alpha
      glucosidase, pancreatic lipase, and tyrosinase inhibition activities, and the MAE
      extract showed even better alpha-glucosidase inhibitory activity than acarbose.

PMID- 30195524
TI  - Comparison of phytochemical profiles and antiproliferative activities of
      different proanthocyanidins fractions from Choerospondias axillaris fruit peels.
AB  - Epidemiological studies had indicated that the incidence of colorectal cancer is
      inversely correlated to the consumption of proanthocyanidins (PAs). In this
      study, five PAs fractions isolated from Choerospondias axillaris fruit peels with
      different mean degree of polymerization (mDP) were characterized and their
      antiproliferative effects on Caco-2 cells were investigated. MALDI-TOF-MS results
      indicated that PAs fractions were composed of procyanidins with DP up to 13-mers.
      All PAs fractions induced dose and time-dependent reductions of Caco-2 cell
      viability. The IC50 values of PAs fractions with increasing mDP were 240 +/-
      16.0, 143 +/- 9.53, 87.0 +/- 3.55, 44.3 +/- 4.89, and 42.8 +/- 2.20 MUg/mL after
      24 h incubation, respectively. The observed reduction in Caco-2 cell viability
      was due to apoptosis via the activation of caspase-9, caspase-3, caspase-8 and
      the elevation of intracellular ROS generation. Moreover, the extent of the
      reduction in cell viability after exposure to PAs fractions was positively
      correlated with their mDP and galloylation. These results indicate that
      Choerospondias axillaris peel is a potential source of natural chemopreventive
      agents for the treatment of colorectal cancer.

PMID- 30195525
TI  - Lab-made electronic-nose with polyaniline sensor array used in classification of
      different aromas in gummy candies.
AB  - Aroma is closely related to the food product acceptability and an important
      product quality indicator. Electronic-nose (E-nose) systems are an interesting
      alternative to traditional methods of aroma analyses. A lab-made E-nose system
      equipped with an array of sensing units comprised by gold interdigitated
      microelectrodes (IDEs) using polyaniline (Pani) as sensitive layers deposited by
      the in situ and Layer-by-layer (LbL) methods was used to analyze aromas in gummy
      candies. Different concentrations from artificial aromas (apple, strawberry and
      grape), added to the gummy candies were evaluated. Our system presented 21.6
      mV.ppb-1 sensitivity, ppb range detection limit, and good reversibility, around
      97.6%. The sensitive layers of Pani films was adequate deposited on IDEs observed
      by the Attenuated Total Reflection/Fourier-transform infrared spectroscopy
      (ATR/FTIR). Linear Discriminant Analysis (LDA) was able to classify apple,
      strawberry, and grape aromas added to gummy candies using saturation potential
      values from the E-nose system, demonstrating its applicability in food matrices.

PMID- 30195526
TI  - A systematic characterization of the distribution, biofilm-forming potential and
      the resistance of the biofilms to the CIP processes of the bacteria in a milk
      powder processing factory.
AB  - Owing to the resistance to conventional cleaning and sanitizing agents, biofilms
      formed on surfaces of dairy processing equipment pose a hazard to the dairy
      industry. The objective of this study was to evaluate the diversity of the
      microflora attached to various surfaces of the processing lines of a milk powder
      processing factory based on 16S rRNA gene sequence analysis. The production of
      biofilms by the bacterial strains was evaluated on polystyrene (PS) and stainless
      steel (SS) surfaces by crystal violet staining method. Especially, effects of
      temperatures (e.g., 37  degrees C and 55  degrees C) and growth mediums (e.g.,
      nutrient broth, NB; tryptic soy broth, TSB) on the production of biofilms by
      these strains on PS surfaces were explored. Besides, the tolerance of the
      biofilms of the strains to CIP processes (1.5% v/v HNO3 solution or 2.0% w/v NaOH
      solution at 80  degrees C) were analyzed. Forty-five isolates from eleven
      interior surfaces of the facilities were identified and the distribution of
      strains had high species diversity, which indicated that multiple spoilage and
      pathogenic microorganisms remained in milk powder processing lines after CIP
      processes. Bacteria showed higher biofilm-forming abilities on SS compared to PS
      surfaces under the same condition. Moreover, effects of the incubation
      temperature and growth medium on biofilm formation varied between genera,
      species, and strains. One strain of each species with biofilm-forming abilities
      on SS surfaces was selected to check the resistance of their biofilms formed on
      SS coupons to the CIP processes. Biofilms of all of the nine strains were highly
      or moderately alkali and acid resistant, posing a threat to the milk powder
      production. These results suggested that organisms within the biofilm might
      withstand temperature and pH changes better than planktonic organisms. More
      research is needed to investigate different species isolated from different
      facilities of the processing lines and to improve the key controlling points in
      the CIP processes.

PMID- 30195527
TI  - Extraction, purification and characterization of pectin from alternative sources
      with potential technological applications.
AB  - Pectins are defined as a group of widely distributed plant cell wall
      polysaccharides that contain galacturonic acid linked at both the 1 and 4
      positions. The wide use of pectin as an ingredient which imparts rheological and
      textural properties to various food products and the development of applications
      beyond the food industry have brought about its increase in production and
      influenced research towards alternative sources and improving the overall
      isolation process of pectic polysaccharides. In this context, this paper aims to
      give a complete perspective on the current state of pectin research by mainly
      focusing on recent research on the extraction of pectin from other feasible
      sources, on the post-extraction stages of pectin recovery from plant materials
      (purification and fractionation), and, finally, on the advancements in the study
      of the physical, chemical, rheological, and functional properties of pectin.

PMID- 30195528
TI  - Solid lipid microparticles loaded with cinnamon oleoresin: Characterization,
      stability and antimicrobial activity.
AB  - Cinnamon bark oleoresin (CO) is a natural flavoring that has several biological
      properties and can act as an antimicrobial agent. However, oleoresins are
      susceptible to degradation by light, oxygen and temperature. Thus, the objective
      of this work was the production and characterization of microparticles loaded
      with CO obtained by the spray chilling technique. Hardfat (PH) and palm oil (PO)
      were used as carriers in different proportions: 100:0; 80:20; 60:40,
      respectively. The active concentration was 1 and 2%. Solid lipid microparticles
      (SLM) were stored at 25 and 45 degrees C having their polymorphism, retention
      capacity of the volatile compounds and antimicrobial capacity assessed over 28
      days. CO presented cinnamaldehyde (Cn), O-methoxy cinnamaldehyde (OmCn) and
      coumarin (Co) as the major volatile components. The minimum inhibitory
      concentration (MIC) of the CO against molds, yeasts and Gram-negative bacteria
      was of 0.1% (v/v), for every microorganism. In the SLM characterization there was
      a significant size variation, with a mean diameter (d 0.5) in the range of 8-72
      MUm. Most of the formulations showed crystals in the polymorphic form beta '. The
      formulation containing only PH as the carrier agent and 2% CO was able to better
      retain the volatile compounds. During the storage period, formulations F2 and F3,
      containing proportions of HP and OP of 80:20 and 60:40, respectively, and 2% CO,
      showed the best stabilities in relation to the concentration of Cn. The
      antimicrobial activity of the SLM against Candida pseudointermedia and
      Penicillium paneum, evaluated by the diameter of inhibition zone, increased over
      the 28 days of storage.

PMID- 30195529
TI  - Grape pomace in ewes diet: Effects on meat quality and the fatty acid profile of
      their suckling lambs.
AB  - Grape pomace (GP) is an inexpensive natural antioxidant promising as animal feed
      supplement due to its high content of phenolic compounds. In order to evaluate
      its effect in lactating ewe rations on meat quality and fat composition of their
      suckling lambs, 48 Churra ewes were divided into 4 treatments. All animals were
      fed a ration containing linseed oil (Control) supplemented with Vitamin E or two
      levels of GP. Lambs were nourished exclusively by suckling until they were
      slaughtered. Dietary GP did not generate adverse effects on carcasses or lambs
      meat quality when compared with Control or Vit-E diets. GP improved the water
      holding capacity of the meat. In addition, lambs meat FA profile was not
      nutritionally affected with the diets assayed. Hence, the use of GP as a dietary
      supplement in ewe rations would not have negative effects on meat from suckling
      lambs.

PMID- 30195530
TI  - Crystallization behavior of emulsified fats influences shear-induced partial
      coalescence.
AB  - Emulsion stability is desired during production, storage and transportation.
      However, controlled destabilization by partial coalescence is requisite in the
      production of e.g. whipped cream, vegetable toppings and ice cream. Partial
      coalescence in recombined cream (RC) implies the presence of a semisolid fat.
      Three types of fat, i.e. anhydrous milk fat (AMF), palm oil (PO) and palm kernel
      oil (PKO), were used in the production of RC. Partial coalescence was initiated
      by the application of shear and assessed at three temperatures, namely 15, 20 and
      25  degrees C to investigate the relation between solid fat content (SFC) and
      shear-induced partial coalescence. Despite differences in SFC, shear-induced
      partial coalescence occurred fastest at 20  degrees C. On the contrary, a nearly
      equal SFC at 25  degrees C resulted in significantly different behavior amongst
      the fats. This demonstrates that not only SFC determines instability but also fat
      crystal microstructure, which is dependent on fat composition and on processing
      conditions. However, SFC could be related to the type of network formed by the
      partially coalesced fat droplets. The fat crystallization properties, studied in
      bulk and emulsion, point out a divergent effect of emulsification on the
      crystallization of the fats which could be explained by differences in crystal
      morphology.

PMID- 30195531
TI  - Profiling of bacterial and fungal communities of Mexican cheeses by high
      throughput DNA sequencing.
AB  - Cheese is a live food whose preparation involves procedures and microbial
      communities playing an important role for the final product. We characterized the
      bacterial and fungal diversity of seventeen different Mexican cheeses by high
      throughput DNA sequencing of 16S/18S rDNA libraries. We propose the existence of
      bacterial and fungal core communities, where at genera level, bacteria include
      Streptococcus spp., Lactococcus spp., Lactobacillus spp., Aerococcus spp., and
      Weisella spp. while at species level, the fungal community includes Galactomyces
      reessii, Scheffersomyces stipitis, Saccharomyces cerevisiae (baker's yeast), and
      S. cerevisiae_rm11-1a. In addition to the bacterial and fungal core communities,
      we found members of the cheese microbiota that could be associated to other
      factors of the cheese manufacturing process. Co-occurrence analysis made in this
      work, indicates that bacterial and fungal communities maintain positive and
      negative interactions which are important to shape the resident microbial
      communities in cheeses. This work is a contribution to the description of the
      microbial diversity found in some Mexican cheeses.

PMID- 30195532
TI  - Combining untargeted, targeted and sensory data to investigate the impact of
      storage on food volatiles: A case study on strawberry juice.
AB  - An integrated science-based approach, combining analytical and sensorial data and
      different data analysis methods, proved successful to study the impact of storage
      time, storage temperature and oxygen availability on strawberry juice volatiles
      and allowed to get a multi-perspective view on these changes. An untargeted GC-MS
      approach showed that the volatile fraction of shelf-stable strawberry juice
      clearly changed during ambient storage and that oxygen availability (linked to
      the type of bottle) had a limited effect. To gain further insight, several
      characteristic aroma compounds were quantified during storage at ambient (20 
      degrees C) and accelerated (28-42  degrees C) temperatures, kinetic parameters
      were estimated and odour activity values were calculated. The kinetic parameters
      showed that all characteristic aroma compounds changed significantly during
      storage at all temperatures and that the rate of change in some compounds was
      accelerated by storage at higher temperatures. The observed changes in strawberry
      juice volatiles caused sensorial differences between non-stored and 20  degrees C
      stored samples as shown by the sensory evaluations and odour activity values.

PMID- 30195533
TI  - Olive oil industry by-products. Effects of a polyphenol-rich extract on the
      metabolome and response to inflammation in cultured intestinal cell.
AB  - Over the past years, researchers and food manufacturers have become increasingly
      interested in olive polyphenols due to the recognition of their biological
      properties and probable role in the prevention of various diseases such as
      inflammatory bowel disease. Olive pomace, one of the main by-products of olive
      oil production, is a potential low-cost, phenol-rich ingredient for the
      formulation of functional food. In this study, the aqueous extract of olive
      pomace was characterized and used to supplement human intestinal cell in culture
      (Caco-2). The effect on the cell metabolome and the anti-inflammatory potential
      were then evaluated. Modification in the metabolome induced by supplementation
      clearly evidenced a metabolic shift toward a "glucose saving/accumulation"
      strategy that could have a role in maintaining anorexigenic hormone secretion and
      could explain the reported appetite-suppressing effect of the administration of
      polyphenol-rich food. In both basal and inflamed condition, supplementation
      significantly reduced the secretion of the main pro-inflammatory cytokine, IL-8.
      Thus, our data confirm the therapeutic potential of polyphenols, and specifically
      of olive pomace in intestinal bowel diseases. Although intervention studies are
      needed to confirm the clinical significance of our findings, the herein reported
      results pave the road for exploitation of olive pomace in the formulation of new,
      value-added foods. In addition, the application of a foodomics approach allowed
      observing a not hypothesized modulation of glucose metabolism.

PMID- 30195534
TI  - Metabolism of Schizosaccharomyces pombe under reduced osmotic stress conditions
      afforded by fed-batch alcoholic fermentation of white grape must.
AB  - Strains of Schizosaccharomyces pombe are being increasingly investigated with
      regards to their grape winemaking potential either in combination with the
      typical production yeast, Saccharomyces cerevisiae, or in monoseptic
      fermentations. Their ethanol tolerance and ability to degrade L-malic acid is
      oenologically convenient but contrasts with the comparatively high acetic acid
      and acetaldehyde formation potential which is considered undesirable, especially
      in white winemaking. The purpose of this work was to investigate the performance
      of a selected S. pombe strain in monoseptic femerntations of white grape must.
      Traditional batch fermentations were compared with an innovative and automated
      fed-batch fermentation technique were sugar concentrations are kept low during
      fermentations to decrease sugar induced osmotic stress. Because of its known
      effect on growth and ethanol tolerance, the effect of Mg was also tested. While
      Mg supplementation was not shown to significantly influence residual values of
      sugars, ethanol, glycerol, organic acids and acetaldehyde, the application of the
      fed-batch technique led to a fundamental change in yeast physiology. While
      glycerol values were only slightly reduced, the fed-batch approach allowed
      obtaining wines devoid of acetic acid whose levels were considerable in wines
      produced by the traditional batch technique (0.6 g/L). The work demonstrates that
      the acetic acid metabolism of S. pombe is associated to sugar induced osmotic
      stress such as for S. cerevisiae, too, and may be controlled by application of
      suitable fermentation techniques for winemaking.

PMID- 30195535
TI  - Untargeted metabolomics reveals differences in chemical fingerprints between PDO
      and non-PDO Grana Padano cheeses.
AB  - The purpose of this preliminary study was to discriminate the chemical
      fingerprints of Protected Designation of Origin (PDO) Grana Padano cheeses from
      non-PDO "Grana-type" cheeses by means of an untargeted metabolomic approach based
      on ultra-high-pressure liquid chromatography coupled to quadrupole time-of-flight
      mass spectrometer (UHPLC/QTOF-MS). Hierarchical cluster analysis and Orthogonal
      Projections to Latent Structures Discriminant Analysis (OPLS-DA) allowed
      discriminating PDO vs. non-PDO cheeses. Lipids (fatty acids and their
      derivatives, phospholipids and monoacylglycerols), amino acids and oligopeptides,
      together with plant-derived compounds were the markers having the highest
      discrimination potential. It can be postulated that Grana Padano value chain, as
      strictly defined in the PDO production specification rules, can drive the
      biochemical processes involved in cheese making and ripening in a distinct
      manner, thus leaving a defined chemical signature on the final product. These
      preliminary findings provide the basis for further authenticity studies, aiming
      to protect the designation of origin of PDO Grana Padano cheese by applying a
      comprehensive foodomics-based approach.

PMID- 30195536
TI  - Differentiation of key biomarkers in tea infusions using a target/nontarget gas
      chromatography/mass spectrometry workflow.
AB  - Climatic conditions affect the chemical composition of edible crops, which can
      impact flavor, nutrition and overall consumer preferences. To understand these
      effects new data analysis software capable of tracking hundreds of compounds
      across years of samples under various environmental conditions is needed. Our
      recently developed mass spectral (MS) subtraction algorithms have been used with
      spectral deconvolution to efficiently analyze complex samples by 2-dimensional
      gas chromatography/mass spectrometry (GC-GC/MS). In this paper, we address the
      accuracy of identifying target and nontarget compounds by GC/MS. Findings
      indicate that Yunnan tea contains higher concentrations of floral compounds. In
      contrast, Fujian tea contains higher concentrations of compounds that exhibit
      fruity characteristics, but contains much less monoterpenes. Principal components
      analysis shows that seasonal changes in climate impact tea plants similarly
      despite location differences. For example, spring teas contained more of the
      sweet, floral and fruity compounds compared to summer teas, which had higher
      concentrations of green, woody, herbal compounds.

PMID- 30195537
TI  - Lactobacillus reuteri growth and fermentation under high pressure towards the
      production of 1,3-propanediol.
AB  - Lactobacillus reuteri is a lactic acid bacterium able to produce several relevant
      bio-based compounds, including 1,3-propanediol (1,3-PDO), a compound used in food
      industry for a wide range of purposes. The performance of fermentations under
      high pressure (HP) is a novel strategy for stimulation of microbial growth and
      possible improvement of fermentation processes. Therefore, the present work
      intended to evaluate the effects of HP (10-35 MPa) on L. reuteri growth and
      glycerol/glucose co-fermentation, particularly on 1,3-PDO production. Two
      different types of samples were used: with or without acetate added in the
      culture medium. The production of 1,3-PDO was stimulated at 10 MPa, resulting in
      enhanced final titers, yields and productivities, compared to 0.1 MPa. The
      highest 1,3-PDO titer (4.21 g L-1) was obtained in the presence of acetate at 10
      MPa, representing yield and productivity improvements of ~ 11 and 12%,
      respectively, relatively to the same samples at 0.1 MPa. In the absence of
      acetate, 1,3-PDO titer and productivity were similar to 0.1 MPa, but the yield
      increased ~ 26%. High pressure also affected the formation of by-products
      (lactate, acetate and ethanol) and, as a consequence, higher molar ratios 1,3
      PDO:by-products were achieved at 10 MPa, regardless of the presence/absence of
      acetate. This indicates a metabolic shift, with modification of product
      selectivity towards production of 1,3-PDO. Overall, this work suggests that HP
      can be a useful tool to improve of 1,3-PDO production from glycerol by L.
      reuteri, even if proper process optimization and scale-up are still needed to
      allow its industrial application. It also opens the possibility of using this
      technology to stimulate other glycerol fermentations processes that are relevant
      for food science and biotechnology.

PMID- 30195538
TI  - The effect of music on gelato perception in different eating contexts.
AB  - This study highlights the effect of music on flavour dynamics under three
      different environmental conditions (laboratory, immersive, and natural eating
      environment). Music valence, the pleasantness of three environments, as well as
      participants' affective state and emotional responses to chocolate gelato while
      listening to music, were all measured. The perception of chocolate gelato flavour
      across the different eating environments was measured using the Temporal Check
      All That Apply (TCATA) method under disliked, neutral, and liked music
      conditions, and a control (silent) condition. Citations in TCATA represent the
      number of panellist agreeing that a specific sensation or perception occurred at
      a specific time point. Results showed that cocoaness, sweetness, and milkiness
      were cited more in the natural eating environment than the laboratory setting,
      and bitterness and creaminess the least cited. The cited attributes in the
      immersive environment were similar to the natural eating environment. Liked and
      neutral music increased sweetness citations, whereas disliked music increased
      bitterness citations.

PMID- 30195539
TI  - Tucum-do-cerrado (Bactris setosa Mart.) may enhance hepatic glucose response by
      suppressing gluconeogenesis and upregulating Slc2a2 via AMPK pathway, even in a
      moderate iron supplementation condition.
AB  - Dietary phytochemicals may improve glucose metabolism while iron excess seems to
      be associated to impaired glucose homeostasis and insulin responses. This study
      investigated the effect of tucum-do-cerrado (Bactris setosa Mart.) consumption on
      the carbohydrate metabolism and redox response in rats supplemented or not with
      dietary iron. Male wistar rats were treated with one of the following diets: CT:
      control diet (AIN- 93G); +Fe: iron-enriched diet; Tuc: control diet +15% tucum-do
      cerrado or Tuc + Fe: iron-enriched diet +15% tucum-do-cerrado. Iron
      supplementation increased muscle lipid and protein oxidation, hepatic glucokinase
      (GK) and phosphofrutokinase 1 (PFK1) activities and decreased hepatic glucose-6
      phosphatase (G6Pase), intestinal Scl2a2 and muscle Slc2a4 and Prkaa2alpha mRNA
      levels compared to CT group. Tucum-do-cerrado consumption (Tuc) increased hepatic
      Slc2a2, Prkaa1alpha, Prkaa2alpha and intestinal Slc5a1 mRNA levels, also
      decreased hepatic G6Pase activity, muscle Slc2a4 and Prkaa2alpha in relation to
      CT group. The association of tucum-do-cerrado with iron-enriched diet increased
      hepatic Prkaa1 and Pck1 compared to the CT and + Fe groups, intestinal Slc2a2
      mRNA levels compared to the +Fe group, while decreased hepatic G6Pase activity in
      relation to the CT, +Fe and Tuc + Fe groups and muscle Slc2a4 and Prkaa2alpha
      compared to CT group. These results suggest that tucum-do-cerrado consumption
      might induce Prkaa1alpha and Prkaa2alpha expression, which may inhibit
      gluconeogenic rate limiting enzyme, G6Pase, and upregulates GLUT2 hepatic glucose
      uptake. In addition, moderate iron supplementation improves intracellular hepatic
      glucose response, stimulating the glycolytic rate limiting enzymes GK and PFK1
      while inhibiting gluconeogenic enzyme G6Pase.

PMID- 30195540
TI  - Kinetic study of enzymatic alpha-galactoside hydrolysis in cowpea seeds.
AB  - The endogenous alpha-galactosidase activity of cowpea seeds was characterized and
      modelled assuming Michaelian behavior. The aim is to use the resulting knowledge
      to optimize alpha-galactoside degradation during the soaking-cooking process. In
      this study, the alpha-galactosidase enzyme from Wankoun cowpea was extracted and
      its enzymatic activity was analyzed as a function of temperature, pH and the
      presence of some inhibitors. Enzymatic activity was optimal around 35  degrees C
      and a pH of 5.8. Activation and inactivation energy was evaluated at 50 +/- 3 and
      103 +/- 9 kJ.mol-1, respectively. The strongest inhibitor was galactose with an
      inhibition constant KI of 0.28 +/- 0.03 mM. Incubation of the enzyme extract with
      alpha-galactosides revealed a 10-h lag phase in the early stages that could be
      due to low pH, the action of inhibitors including galactose and the biosynthesis
      of alpha-galactosides. After the lag phase, the degradation of each alpha
      galactoside occurred without the appearance of any intermediary product. The
      degradation of alpha-galactosides was observed with a Km of 1.7 +/- 0.3 mM for
      raffinose; 3.6 +/- 0.6 mM for stachyose and 15.9 +/- 0.1 mM for verbascose. A
      long soaking step around 35  degrees C is suggested to maximize the alpha
      galactosides enzymatic degradation.

PMID- 30195541
TI  - Chlorogenic and phenolic acids are only very weak inhibitors of human salivary
      alpha-amylase and rat intestinal maltase activities.
AB  - There is increasing evidence that consumption of polyphenol and phenolic-rich
      foods and beverages have the potential to reduce the risk of developing diabetes
      type 2, with coffee a dominant example according to epidemiological evidence. One
      of the proposed mechanisms of action is the inhibition of carbohydrate-digesting
      enzymes leading to attenuated post-prandial blood glucose concentrations, as
      exemplified by the anti-diabetic drug, acarbose. We determined if the phenolic, 5
      caffeoylquinic acid, present in coffee, apples, potatoes, artichokes and prunes,
      for example, and also selected free phenolic acids (ferulic acid, caffeic acid
      and 3,4-dimethoxycinnamic acid), could inhibit human salivary alpha-amylase and
      rat intestinal maltase activities, digestive enzymes involved in the degradation
      of starch and malto-oligosaccharides. Using validated assays, we show that
      phenolic acids, both free and linked to quinic acid, are poor inhibitors of these
      enzymes, despite several publications that claim otherwise. 5-CQA inhibited human
      alpha-amylase only by <20% at 5 mM, with even less inhibition of rat intestinal
      maltase. The most effective inhibition was with 3,4-dimethoxycinnamic acid
      (plateau at maximum 32% inhibition of human alpha-amylase at 0.6 mM), but this
      compound is found in coffee in the free form only at very low concentrations.
      Espresso coffee contains the highest levels of 5-CQA among all commonly consumed
      foods and beverages with a typical concentration of ~5 mM, and much lower levels
      of free phenolic acids. We therefore conclude that inhibition of carbohydrate
      digesting enzymes by chlorogenic or phenolic acids from any food or beverage is
      unlikely to be sufficient to modify post-prandial glycaemia, and so is unlikely
      to be the mechanism by which chlorogenic acid-rich foods and beverages such as
      coffee can reduce the risk of developing type 2 diabetes.

PMID- 30195543
TI  - Emulsion gels containing n-3 fatty acids and condensed tannins designed as
      functional fat replacers.
AB  - The purpose of this study was to ascertain the potential of several food-grade
      emulsion (O/W) gels (GEs) for use as healthier fat replacers. The emulsions,
      formulated with a lipid phase rich in n-3 fatty acids and different emulsifiers
      (sodium caseinate, SC; whey protein isolate, WPI and isolated soy protein, ISP),
      were cold gelled after adding a natural extract rich in condensed tannins (CT).
      The GEs were characterized and their oxidative stability evaluated during storage
      (4  degrees C). All GEs formulated presented a solid-like structure showing
      generally excellent emulsion stability, which improved in GEs with the addition
      of CT. Non-extractable proanthocyanidins (NEPA) were the main source of
      polyphenol in samples enriched with CTs. The antioxidant activity of the systems
      was not affected by the use of different proteins as emulsifiers, but it was
      improved in GEs containing CT. The oxidation values recorded in the GE systems
      can generally be regarded as low even considering their enrichment with
      unsaturated fatty acids, which thus assures their suitability for use as fat
      replacers.

PMID- 30195542
TI  - Distribution and tracking of Clostridium difficile and Clostridium perfringens in
      a free-range pig abattoir and processing plant.
AB  - The presence and genetic diversity of Clostridium difficile and C. perfringens
      along the slaughtering process of pigs reared in a free-range system was
      assessed. A total of 270 samples from trucks, lairage, slaughter line and
      quartering were analyzed, and recovered isolates were toxinotyped and genotyped.
      C. difficile and C. perfringens were retrieved from 14.4% and 12.6% of samples,
      respectively. The highest percentage of positive samples for C. difficile was
      detected in trucks (80%) whereas C. perfringens was more prevalent in cecal and
      colonic samples obtained in the slaughter line (85% and 45%, respectively). C.
      difficile isolates (n = 105) were classified into 17 PCR ribotypes (including
      010, 078, and 126) and 95 AFLP genotypes. C. perfringens isolates (n = 85)
      belonged to toxinotypes A (94.1%) and C (5.9%) and were classified into 80 AFLP
      genotypes. The same genotypes of C. difficile and C. perfringens were isolated
      from different pigs and occasionally from environmental samples, suggesting a
      risk of contaminated meat products.

PMID- 30195544
TI  - Previously undescribed antioxidative O-heterocyclic angiotensin converting enzyme
      inhibitors from the intertidal seaweed Sargassum wightii as potential
      antihypertensives.
AB  - Four previously undescribed antioxidative O-heterocyclic analogues, characterized
      as 3"-isopropyl-3c-{3b-[(2-oxo-3,4-dihydro-2H-chromen-3-yl) methyl] butyl}-2"
      butenyl-3'-hydroxy-2'-(2'b-methoxy-2'-oxoethyl)-3', 4'-dihydro-2H-pyran-4'
      carboxylate (1), 2c-methylbutyl-6-[6c-(benzoyloxy)propyl]-6-methyl-tetrahydro-2H
      pyran-2-carboxylate (2), 6-{6b-[3'-(5'a-methyl propyl)-3', 4'-dihydro-2H-pyran-6'
      yl] ethyl}-tetrahydro-2H-pyran-2-one (3) and 7-(7c-methylpentyl)-hexahydro-2H
      chromen-2-one (4) were isolated from the ethylacetate:methanol fraction of the
      brown seaweed Sargassum wightii. Nuclear magnetic resonance and mass
      spectroscopic experiments unambiguously attributed their structural identities.
      Antihypertensive activities of the studied compounds were determined in terms of
      their angiotensin converting enzyme (ACE) inhibitory potential. The 2H
      pyranylcarboxylate derivative (1) displayed comparable activity (IC50 0.08 mg/mL)
      with standard antihypertensive agent captopril (IC50 0.07 mg/mL). The O
      heterocyclic derivatives bearing 2H-pyran-4'-carboxylate (1) and 2H-pyran-2
      carboxylate (2) frameworks showed significantly greater (p < 0.05) 1, 1-diphenyl
      2-picryl-hydrazil radical quenching potential {IC50 (1) 0.34 and IC50 (2) 0.45
      mg/mL} compared to the standard antioxidant alpha-tocopherol (IC50 0.63 mg/mL).
      Structure-activity relationship analyses demonstrated that the electronic and
      lipophilic descriptors might significantly contribute towards the target
      bioactivities of 2H-pyranylcarboxylates (1 and 2). Molecular docking simulations
      were carried out for ACE inhibition, and the binding energy obtained for the
      compounds (~7.04-8.48 kcal/mol) demonstrated their potential enzyme-ligand
      interactions. The potential of hitherto undescribed O-heterocyclic derivatives as
      natural antioxidant and antihypertensive functional food supplements and their
      utilization as therapeutic leads in the antihypertensive management were
      described in the present study.

PMID- 30195545
TI  - Influence of malt source on beer chemistry, flavor, and flavor stability.
AB  - Beverage quality in the brewing industry is heavily influenced by ingredient
      properties. The contribution of raw ingredients such as yeast and hops to beer
      flavor is well understood. However, the influence of barley genotype and/or
      environment on flavor (the malt 'source') is largely unexplored. Here, a study
      was performed to determine (i) if there are metabolite differences among six
      commercial malt sources, (ii) if differences in malt chemistry are reflected in
      the chemistry of the beer, and (iii) if the differences in the beer chemistry
      impact sensory attributes of beer, through flavor and flavor stability. Six
      distinct sources of malts (six varieties from three maltsters) were brewed into
      six beers using a recipe designed to evaluate differences in flavor. Metabolomics
      and ionomics was used to characterize chemical variation among the six malts and
      beers using UHPLC- and HILIC-MS (non-volatile metabolites), HS-SPME/GC-MS (beer
      volatiles), and ICP-MS (malt metals). These analyses detected a total of 5042
      compounds in malt, of which 217 were annotated and included amines, amino acids,
      fatty acids/lipids/fatty acyls, saccharides/glucosides/sugar acids/sugar
      alcohols, carboxylic acid derivatives, organic acids, phenolics/benzenoids,
      purines, pyrimidines/pyridines, terpenes, and organosulfurs. A total of 4568
      compounds were detected in beer, of which 246 were annotated and included esters,
      aldehydes, and alcohols. Statistical analysis revealed chemical variation among
      the six malts (50/217 malt metabolites varied) and beers (150/246). The six beers
      were evaluated for flavor using a modified descriptive analysis for 45 sensory
      traits at 0, 4, and 8 weeks of storage at 4  degrees C. Principal component
      analysis of the sensory data revealed flavor differences among the six beers at 8
      weeks, and the malt-type Full Pint was described as fruity and Meredith as corn
      chip. The metabolite and sensory data were integrated and revealed associations
      between flavor profiles in beer and the annotated malt and beer. The fruity or
      corn chip flavor profiles in beer were associated beer purines/pyrimidines,
      volatile ketones, amines, and phenolics, and malt lipids, saccharides, phenols,
      amines, and alkaloids. Taken together, these data support a role of malt source
      in beer flavor and flavor stability. As a raw ingredient, malting barley
      genotypes can be evaluated for a contribution to flavor, and this may be a future
      target for plant breeding, agronomy, and malting efforts to selectively improve
      flavor, flavor stability, and quality in beer.

PMID- 30195546
TI  - Bioactive compounds and protective effect of red and black rice brans extracts in
      human neuron-like cells (SH-SY5Y).
AB  - Rice bran is obtained from the rice polishing process, and this by-product
      contains many bioactive compounds. In this study, the composition of phenolic
      compounds from red and black rice brans was determined by HPLC-DAD-MS.
      Additionally, the neuroprotective ability of these brans in SH-SY5Y cells
      insulted with hydrogen peroxide (H2O2) was evaluated. The phenolic constituents
      of rice bran were separated into hydrophilic and pellet fractions. The major
      phenolic compound in both samples was ferulic acid. Cyanidin 3-glucoside was the
      main anthocyanin in black rice bran. The hydrophilic and pellet fractions showed
      a protective effect (38-94%) on SH-SY5Y cells insulted by H2O2 in DCFH-DA assay.
      No extract showed cytotoxicity in the SRB assay. These results suggest a
      neuroprotective effect of red and black rice brans extracts due to their high
      antioxidant capacity, along with the absence of cytotoxicity. Thus, they may
      potentially be used as sources of bioactive compounds.

PMID- 30195547
TI  - Development of alginate-pectin microparticles with dairy whey using vibration
      technology: Effects of matrix composition on the protection of Lactobacillus spp.
      from adverse conditions.
AB  - In this study, lactic acid bacteria with probiotic potential, including
      Lactobacillus plantarum ATCC8014, L. paracasei ML33 and L. pentosus ML82, were
      encapsulated with whey-alginate-pectin (WAP) or whey permeate-alginate-pectin
      (PAP) by an extrusion process using vibrational technology, with the resulting
      microparticles assessed for their resistance to adverse conditions. The aim was
      to assess the effect of the encapsulation wall materials on the viability of
      microorganisms, the encapsulation, refrigerated storage and simulated
      gastrointestinal tract conditions, the kinetic parameters of acidification, and
      the morphology of microparticles. The bacteria encapsulated with the WAP wall
      material were adequately protected. Furthermore, after three months of storage at
      4  degrees C, the encapsulated bacteria exhibited a cell viability of >6 log CFU
      mL-1. In addition, the encapsulated L. plantarum ATCC8014 and L. pentosus ML82
      isolates exhibited the highest viability at the end of the storage period among
      the assayed isolates. Encapsulated bacteria showed greater resistance to acidic
      conditions than unencapsulated bacteria when exposed to simulated
      gastrointestinal tract conditions. The maximum rate of milk acidification by
      encapsulated Lactobacillus spp. was approximately three-fold lower than that
      observed for unencapsulated bacteria. The resulting size of the microparticles
      generated using both combinations of wall materials used was approximately 150
      MUm. The cheese whey and whey permeate combined with alginate and pectin to
      adequately encapsulate and protect Lactobacillus spp. from the adverse conditions
      of the simulated gastrointestinal tract and from refrigeration storage
      temperatures. Furthermore, the sizes of the obtained microparticles indicated
      that the encapsulated materials are suitable for being incorporated into foods
      without changing their sensory properties.

PMID- 30195549
TI  - Relationship between fatty acids intake and Clostridium coccoides in obese
      individuals with metabolic syndrome.
AB  - Dietary habits exert a strong influence on gut microbial composition and may
      result in an imbalance of gut microbes, representing a predisposition to obesity
      and metabolic disorders. We aimed to investigate a potential relationship between
      gut bacterial species and metabolic parameters and dietary intake. Bacterial DNA
      was extracted from feces of 34 obese subjects with and without metabolic syndrome
      (MS and n-MS group, respectively). We then used real-time polymerase chain
      reaction (qPCR) for quantifying specific sequences to Akkermansia muciniphila,
      Bifidobacterium spp., Clostridium coccoides, and Lactobacillus spp. and analyzed
      them with respect to clinical characteristics. Our data showed that the MS group
      had a 6.7-fold higher level of C. coccoides in their stool samples than the n-MS
      group. The abundance of C. coccoides was positively correlated with a high intake
      of monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids.
      Furthermore, an excessive dietary level of MUFA was identified as a predictor of
      C. coccoides abundance. Alterations in the gut microbial ecology were positively
      correlated with levels of triacylglycerol in obese individuals. Therefore, the
      type and quantity of dietary fat may alter the gut microbial ecology in obese
      individuals with MS and may predispose them to dyslipidemia.

PMID- 30195548
TI  - Aflatoxin in foodstuffs: Occurrence and recent advances in decontamination.
AB  - Aflatoxins are highly toxic compounds produced as secondary metabolites by some
      Aspergillus species, whose occurrence have been reported predominantly in several
      types of foods of low moisture content, while aflatoxin biotransformation
      products have been reported mainly in milk and milk products. This review deals
      with the occurrence of aflatoxins in some of the major food products in the last
      5 years including regulatory aspects, and recent advances in detoxification
      strategies for contaminated foods. Aflatoxin contamination in cereals including
      corn and peanut is still a public health problem for some populations, especially
      in African countries. Despite that most of physical and chemical methods for
      aflatoxin detoxification may affect the nutritional properties of food, or are
      not safe for human consumption, gamma-radiation and ozone applications have
      demonstrated great potential for detoxification of aflatoxins in some food
      matrices. Biological methods based on removal or degradation of aflatoxins by
      bacterial and yeast have good perspectives, although further studies are needed
      to clarify the detoxification mechanisms by microorganisms and determine
      practical aspects of the use of these methods in food products, especially their
      potential effects on sensory characteristics of foods.

PMID- 30195550
TI  - PARAFAC HPLC-DAD metabolomic fingerprint investigation of reference and crossed
      coffees.
AB  - In this study two cultivars of Coffea arabica L., Bourbon (reference) and IPR101
      (crossing) were analyzed. The extracts were prepared according to a simplex
      centroid design with four components, ethanol, ethyl acetate, dichloromethane,
      and hexane. Multiway data were obtained by HPLC-DAD analysis of the fifteen
      different mixtures for each cultivar. The PARAFAC methodology was used to
      investigate the chromatographic fingerprint. For both cultivars, Factor 1 was
      able to discriminate mixtures containing ethyl acetate as solvent. Factor 2
      indicated that mixtures in pure ethanol and binary mixtures containing ethanol
      were the most efficient in extracting chlorogenic acids and factor 3 identified
      methylxanthines through spectrophotometric profile in all mixtures. Higher
      concentrations were obtained by the ethanol, dichloromethane and hexane ternary
      mixture for the Bourbon cultivar and by the quaternary mixture of these solvents
      with ethyl acetate for the IPR101 cultivar. Trigonelline and cafestol were
      extracted in both cultivars. The reference coffee showed higher relative
      abundances of cafestol ester, chlorogenic acids and trigonelline whereas the
      crossed coffee showed higher levels of caffeine. To confirm these results, UPLC
      MS was used as a complementary method to confirm the presence of the metabolites
      in these extracts. The three way PARAFAC strategy determines correlations of HPLC
      DAD chromatographic and spectral data simultaneously with samples permitting a
      more unambiguous assignment of metabolic groups than can be obtained treating
      chromatographic and spectral data separately by two way methods. This can provide
      higher quality chromatographic fingerprints for food chemistry.

PMID- 30195551
TI  - Active packaging films with natural antioxidants to be used in meat industry: A
      review.
AB  - Spoilage of meat products during processing, distribution and exposure in the
      markets have an important negative impact on meat industry from an economic point
      of view. Two of the main problems of meat and products during processing and
      subsequent storage are lipid oxidation and deterioration due to microorganism
      growth. In this context, several packaging alternatives have been developed by
      meat industry in order to limit these losses and to extend the meat products'
      shelf life. Over the last years, the use of active packaging has been proposed as
      an alternative to traditional packaging. The principle of active packaging,
      particularly antioxidant active packaging, consists of including active agents in
      the packaging which interact with meat and/or its environment, either by trapping
      pro-oxidant compounds or by releasing antioxidant compounds in order to delay
      degradation due to lipid oxidation. Therefore, the use of active packaging is
      presented as a future option to solve the problems derived from oxidative
      deterioration of meat and meat products. However, its use will depend on the
      costs involved in the development of this active packaging. Therefore, this
      review will give an overview about the use of active packaging and natural
      antioxidants, the active film development techniques, as well as the use of
      biopolymers as substitutes for synthetic polymers and their direct application in
      the meat industry.

PMID- 30195553
TI  - Variability in Antibiotic Prescribing for Upper Respiratory Illnesses by Provider
      Specialty.
AB  - OBJECTIVE: To evaluate variation in antibiotic prescribing between pediatric and
      nonpediatric providers for common upper respiratory illnesses. STUDY DESIGN:
      Patient encounters for children aged <18 years from a regional health care system
      were identified. Electronic medical records from 2011 to 2016 were extracted for
      diagnoses of upper respiratory infection, pharyngitis, acute otitis media, and
      sinusitis. Encounters with competing medical diagnoses, recent hospitalization,
      and antibiotic prescriptions within 30 days were excluded. Adherence to
      antibiotic guidelines was assessed by provider training (pediatric, nonpediatric
      physicians, and advance practice providers). Additional factors assessed were
      calendar year, and patient's age, sex, insurance status, and number of sick
      visits in the prior year. RESULTS: Across 6 years, 141 361 visits were examined:
      43 914 for upper respiratory infection, 43 701 for pharyngitis, 43 925 for acute
      otitis media, and 9821 for sinusitis. Pediatricians were more likely than
      Advanced practice providers (APP) and nonpediatric providers to have guideline
      concordant prescribing for pharyngitis (pediatricians, 66.7% [95% CI, 54.5-77.0];
      nonpediatricians, 49.1% [95% CI, 36.3-62.0], APPs, 52.2% [95% CI, 39.4-64.7]; P <
      .0001) and sinusitis (pediatricians, 70.8% [95% CI, 53.8-83.4], nonpediatricians,
      63.3% [95% CI, 46.8-77.2], APPs, 62.1% [95% CI, 45.1-76.5]; P = .48) and to
      withhold antibiotics for upper respiratory infection than APPs and nonpediatric
      providers (pediatricians, 86.6% [95% CI, 81.2-90.6], nonpediatricians, 80.8% [95%
      CI, 73.0-86.8], APPs, 76.8% [95% CI, 68.4-83.5]; P < .0001). Pediatricians were
      less likely to prescribe antibiotics for pharyngitis without a positive test for
      group A Streptococcus than APPs and nonpediatric providers (pediatricians, 15.1%
      [95% CI, 10.4-21.6], nonpediatricians, 29.4% [95% CI, 20.8-39.6], APPs, 27.2%
      [95% CI, 19.3-36.9]; P < .0001). First-line antibiotic prescribing for acute
      otitis media did not differ between provider specialties. A trend toward more
      guideline-concordant prescribing was seen for pharyngitis and sinusitis over the
      study period. CONCLUSIONS: Pediatricians were more likely to adhere to guidelines
      for management of pediatric acute respiratory infections. Pediatric antibiotic
      stewardship efforts should also target nonpediatricians.

PMID- 30195554
TI  - Timing of Information-Seeking about Infant Vaccines.
AB  - OBJECTIVES: To assess among pregnant and recently delivered women the timing of
      thinking about and seeking information about childhood vaccines and the preferred
      modes of vaccine education. STUDY DESIGN: An e-mail survey among women in 9 urban
      and rural obstetrics practices in Colorado was conducted from February to April
      2014, timed so that approximately one-half had delivered and one-half were still
      pregnant, designed to assess the frequency of thinking about and seeking
      information about vaccines in relation to estimated or actual delivery date. A
      shortened version of the Parental Attitudes About Childhood Vaccines scale was
      used to assess vaccine hesitancy. RESULTS: The response rate was 54% (230 of
      425); 56% were pregnant, 44% had delivered, and 18% were vaccine-hesitant.
      Compared with pregnant women, women who had delivered more often reported
      thinking about vaccines for their infant (pregnant: 19% often, 42% sometimes;
      delivered: 29% often, 51% sometimes; P < .05) and looking for information about
      vaccines (pregnant: 6% often, 22% sometimes; delivered: 16% often, 34% sometimes;
      P < .01). Women most frequently reported seeking information about vaccines 2-4
      weeks after delivery, followed by 4-6 weeks after delivery. The most preferred
      method for vaccine education was their child's doctor (95% acceptable; 92% likely
      to use) followed by their obstetrician (79% acceptable; 64% likely to use).
      CONCLUSIONS: Within 6 weeks postdelivery appears to be when the most women seek
      vaccine information. A child's doctor remains the most acceptable source of
      vaccine education.

PMID- 30195552
TI  - Risk of Bacterial Coinfections in Febrile Infants 60 Days Old and Younger with
      Documented Viral Infections.
AB  - OBJECTIVE: To determine the risk of serious bacterial infections (SBIs) in young
      febrile infants with and without viral infections. STUDY DESIGN: Planned
      secondary analyses of a prospective observational study of febrile infants 60
      days of age or younger evaluated at 1 of 26 emergency departments who did not
      have clinical sepsis or an identifiable site of bacterial infection. We compared
      patient demographics, clinical, and laboratory findings, and prevalence of SBIs
      between virus-positive and virus-negative infants. RESULTS: Of the 4778 enrolled
      infants, 2945 (61.6%) had viral testing performed, of whom 1200 (48.1%) were
      virus positive; 44 of the 1200 had SBIs (3.7%; 95% CI, 2.7%-4.9%). Of the 1745
      virus-negative infants, 222 had SBIs (12.7%; 95% CI, 11.2%-14.4%). Rates of
      specific SBIs in the virus-positive group vs the virus-negative group were: UTIs
      (33 of 1200 [2.8%; 95% CI, 1.9%-3.8%] vs 186 of 1745 [10.7%; 95% CI, 9.2%-12.2%])
      and bacteremia (9 of 1199 [0.8%; 95% CI, 0.3%-1.4%] vs 50 of 1743 [2.9%; 95% CI,
      2.1%-3.8%]). The rate of bacterial meningitis tended to be lower in the virus
      positive group (0.4%) than in the viral-negative group (0.8%); the difference was
      not statistically significant. Negative viral status (aOR, 3.2; 95% CI, 2.3-4.6),
      was significantly associated with SBI in multivariable analysis. CONCLUSIONS:
      Febrile infants <=60 days of age with viral infections are at significantly
      lower, but non-negligible risk for SBIs, including bacteremia and bacterial
      meningitis.

PMID- 30195555
TI  - Early Postnatal Ventricular Dysfunction Is Associated with Disease Severity in
      Patients with Congenital Diaphragmatic Hernia.
AB  - OBJECTIVE: To assess patterns of postnatal ventricular function and their
      relationship to prenatal and postnatal markers of disease severity in infants
      with congenital diaphragmatic hernia (CDH). STUDY DESIGN: In this observational
      case-control study of cardiac function in infants with CDH in the first 5 days of
      life, systolic and diastolic function in the right ventricle (RV) and left
      ventricle (LV) were assessed using speckle tracking echocardiography-derived
      global strain and tissue Doppler imaging. Correlation between cardiac function
      and prenatal observed:expected total fetal lung volume (TFLV), oxygenation index
      (OI), duration of intubation, and hospital length of stay were assessed. RESULTS:
      All measures of systolic and diastolic function were significantly reduced in the
      CDH group (n = 25) compared with controls (n = 20) at <48 hours, and were
      improved by 72-120 hours. LV global systolic longitudinal strain (GLS) correlated
      with prenatal TFLV (R2 = 0.32; P = .03), OI (R2 = 0.35; P < .001), duration of
      intubation (R2 = 0.24; P = .04), and length of stay (R2 = 0.4; P = .006). Mean
      (SD) LV GLS at <48 hours was significantly lower in infants with CDH who did not
      survive and/or required ECMO compared with those who did not: -11.5 (5.3)% vs 
      16.9 (5.3)% (P = .02). CONCLUSIONS: RV and LV function are impaired in the
      transitional period in infants with CDH. Early LV systolic function correlates
      with prenatal and postnatal markers of clinical disease severity and may be an
      important determinant of disease severity and therapeutic target in CDH. These
      findings support regular assessment of cardiac function in CDH and
      investigational trials of targeted cardiovascular therapies.

PMID- 30195556
TI  - Familial Risk of Appendicitis: A Nationwide Population Study.
AB  - OBJECTIVE: To investigate the familial risk of appendicitis in the general
      population. STUDY DESIGN: A nationwide, cross-sectional study consisting of 24
      349 599 Taiwan National Health Insurance beneficiaries in 2015 was conducted.
      Among them, 788 042 individuals had at least 1 first-degree relative with
      appendicitis. The familial relative risks (RRs) of appendicitis and familial
      transmission were estimated. RESULTS: The overall RR (95% CI) of appendicitis in
      individuals with any affected first-degree relatives was 1.67 (1.64-1.71)
      compared with the general population. The RRs for individuals with an affected
      twin, sibling, offspring, and parent were 3.40 (2.66-4.35), 1.98 (1.92-2.04),
      1.55 (1.51-1.59), and 1.54 (1.50-1.58), respectively. The RRs for individuals
      with 1, 2, 3 or more affected first-degree relatives were 1.65 (1.62-1.68), 2.63
      (2.37-2.91), and 6.70 (4.22-10.63), respectively. Furthermore, there was an age
      dependent trend of the RRs, with the greatest RR in the youngest group. The
      estimated familial transmission (genetic plus shared environmental contribution
      to the total phenotypic variance of appendicitis) was 23.2%. CONCLUSION:
      Individuals with a family history of appendicitis have an increased risk of
      appendicitis. This risk is age-dependent and related to the genetic distance and
      numbers of affected relatives.

PMID- 30195557
TI  - Energy and Protein Intake During the Transition from Parenteral to Enteral
      Nutrition in Infants of Very Low Birth Weight.
AB  - OBJECTIVE: To evaluate the association between nutrition delivery practices and
      energy and protein intake during the transition from parenteral to enteral
      nutrition in infants of very low birth weight (VLBW). STUDY DESIGN: This was a
      retrospective analysis of 115 infants who were VLBW from a regional neonatal
      intensive care unit. Changes in energy and protein intake were estimated during
      transition phase 1 (0% enteral); phase 2 (>0, <=33.3% enteral); phase 3 (>33.3,
      <=66.7% enteral); phase 4 (>66.7, <100% enteral); and phase 5 (100% enteral).
      Associations between energy and protein intake were determined for each phase for
      parenteral nutrition, intravenous lipids, central line, feeding fortification,
      fluid restriction, and excess non-nutritive fluid intake. RESULTS: In phases 2
      and 3, infants receiving feeding fortification received less protein than infants
      who were unfortified (-1.1 and -0.3 g/kg/d, respectively; P < .001). However,
      this negative association was not observed after adjusting for relevant nutrition
      delivery practices. Despite greater enteral protein intake during phases 2 and 3
      (0.3 and 0.8 g/kg/d, respectively; P < .001), infants with early fortification
      received less parenteral protein than infants who were unfortified (-1.4 and -1.1
      g/kg/d, respectively; P < .001). Similar patterns were observed for energy
      intake. Protein intake declined during phases 3 and 4. CONCLUSIONS: Infants
      paradoxically received less protein and energy on days with early fortification,
      suggesting that clinicians may lack easily accessible data to detect the
      association between nutrition delivery practices and overall nutrition in infants
      who are VLBW.

PMID- 30195558
TI  - Protecting Our Nutrient Safety Net.

PMID- 30195560
TI  - Reply.

PMID- 30195559
TI  - Comorbidities of Rare Epilepsies: Results from the Rare Epilepsy Network.
AB  - OBJECTIVE: To describe the prevalence and characteristics of comorbidities in
      persons with rare epilepsies. STUDY DESIGN: Persons with rare epilepsies and
      caregivers of those affected were recruited through the Epilepsy Foundation and
      more than 30 rare epilepsy advocacy organizations affiliated with the Rare
      Epilepsy Network (REN). A web-based survey was conducted using a questionnaire
      consisting of core sections to collect data from affected persons on various
      aspects, including comorbidities. Comorbidity information was grouped into 15
      classes, 12 of which had a stem question followed by detailed branch questions
      and 3 that were created from a combination of related questions. RESULTS: Of 795
      persons with more than 30 different rare epilepsy diagnosis groups, one-half had
      >=5 comorbidity classes and 97% were classified as complex chronic disease (C
      CD). The highest number of comorbidity classes reported per person were persons
      with Aicardi syndrome, Phelan-McDermid syndrome (median, 7.0; IQR, 5.0-9.0), and
      tuberous sclerosis complex (median, 6.0; IQR, 4.0-8.0). The most common
      comorbidity classes were learning/developmental disability (71%), mental health
      issues (71%), sleep disorders (60%), brain abnormalities (52%), oral issues
      (49%), bone-joint issues (42%), hyper/hypotonia (42%), and eye-vision disorders
      (38%). The prevalence of brain abnormalities, hyper/hypotonia, eye, and cardiac
      disorders was significantly higher in persons first diagnosed with epilepsy at a
      younger age (<9 months) than in those first diagnosed at an older age (P < .05
      for trend). CONCLUSIONS: Nearly all persons with rare epilepsies are medically
      complex, with a high prevalence of multiple comorbidities, especially those who
      were diagnosed with epilepsy in the first year of life. Comorbidities should be
      carefully considered in the diagnosis and management of persons with rare
      epilepsies.

PMID- 30195561
TI  - Improved Outcomes in Preterm Infants Fed a Nonacidified Liquid Human Milk
      Fortifier: A Prospective Randomized Clinical Trial.
AB  - OBJECTIVE: To compare growth, feeding tolerance, and clinical and biochemical
      evaluations in human milk-fed preterm infants randomized to receive either an
      acidified or a nonacidified liquid human milk fortifier. STUDY DESIGN: This
      prospective, controlled, parallel, multicenter growth and tolerance study
      included 164 preterm infants (<=32 weeks of gestation, birth weight 700-1500 g)
      who were randomized to acidified or nonacidified liquid human milk fortifier from
      study day 1, the first day of fortification, through study day 29 or until
      hospital discharge. RESULTS: There was no difference in the primary outcome of
      weight gain from study days 1 to 29 (acidified liquid human milk fortifier, 16.4
      +/- 0.4 g/kg/day; nonacidified liquid human milk fortifier, 16.9 +/- 0.4
      g/kg/day). However, in both the intention-to-treat and the protocol evaluable
      analyses, infants fed nonacidified liquid human milk fortifier had significantly
      greater weight gain from study days 1 to 15 (17.9 g/kg/day vs 15.2 g/kg/day; P =
      .001). Infants fed with acidified liquid human milk fortifier received more
      protein (4.26 vs  g/kg/day 4.11 g/kg/day, P = .0099) yet had lower blood urea
      nitrogen values (P = .010). The group fed acidified liquid human milk fortifier
      had more vomiting (10.3% vs 2.4%; P = .018), gastric residuals (12.8% vs 3.7%; P
      = .022), and metabolic acidosis (27% vs 5%; P < .001) in the intention-to-treat
      analysis and more abdominal distension (14.0% vs 1.7%; P = .015) in the protocol
      evaluable analysis. CONCLUSIONS: Infants fed an acidified liquid human milk
      fortifier had higher rates of metabolic acidosis and poor feeding tolerance
      compared with infants fed a nonacidified liquid human milk fortifier. Initial
      weight gain was poorer with the acidified liquid human milk fortifier. TRIAL
      REGISTRATION: ClinicalTrials.gov: NCT02307760.

PMID- 30195562
TI  - Orgasmic Latency and Related Parameters in Women During Partnered and
      Masturbatory Sex.
AB  - INTRODUCTION: Orgasmic latency (OL) during partnered sex (POL) and OL during
      masturbatory sex (MOL) in women with and without orgasmic difficulty have
      received minimal attention. AIM: To ascertain POL and MOL both overall and more
      specifically in women with and without difficulty reaching orgasm and to explore
      interrelationships between masturbatory and partnered latencies and sexual
      satisfaction. METHODS: Participants for this study were 2,304 women drawn from
      community-based samples in the United States and Hungary who completed an
      investigator-derived questionnaire regarding their sexual history and response,
      including items related to frequency of masturbation and partnered sex, sexual
      desire, sexual arousal, orgasmic response, OL, distress, partner distress, and
      sexual satisfaction. MAIN OUTCOME MEASURE: Self-reported OL and related orgasmic
      parameters during masturbation and partnered sex in women with and without
      difficulty reaching orgasm were assessed. RESULTS: POL were longer than those
      during MOL. Women experiencing difficulty reaching orgasm showed even longer
      latencies during partnered sex but comparable latencies during masturbation.
      Covariates related to POL included age, overall relationship quality,
      masturbation frequency, MOL, and level of distress about not reaching orgasm.
      CLINICAL IMPLICATIONS: POL in women are substantially longer than men's,
      suggesting the potential need for an increased repertoire of stimulatory
      behaviors to increase the woman's arousal. STRENGTH AND LIMITATIONS: The study
      was well powered and drew from a multi-national population. However, specific
      types of sexual stimulation during partnered and masturbatory sex were not
      included in this analysis. CONCLUSION: MOL for women and POL differ
      significantly, with latencies during partnered sex being substantially longer
      than masturbation, although women reporting the greatest difficulty reaching
      orgasm have the longest latencies and are likely to find masturbation more
      satisfying than women who do not. Rowland DL, Sullivan SL, Hevesi K, et al.
      Orgasmic Latency and Related Parameters in Women During Partnered and
      Masturbatory Sex. J Sex Med 2018;15:1463-1471.

PMID- 30195563
TI  - Evidence for a Change in the Sex Ratio of Children Referred for Gender Dysphoria:
      Data From the Gender Identity Development Service in London (2000-2017).
AB  - INTRODUCTION: The prevalence of gender dysphoria in children is not known;
      however, there are some data on the sex ratio of children referred to specialized
      gender identity clinics. AIM: We sought to examine the sex ratio of children, and
      some associated factors (age at referral and year of referral), referred to the
      Gender Identity Development Service in the United Kingdom, the largest such
      clinic in the world. METHODS: The sex ratio of children (N = 1,215) referred to
      the Gender Identity Development Service between 2000-2017 was examined, along
      with year of referral, age-related patterns, and age at referral. MAIN OUTCOME
      MEASURE: Sex ratio of birth-assigned boys vs birth-assigned girls. RESULTS: The
      sex ratio significantly favored birth-assigned boys over birth-assigned girls
      (1.27:1), but there were also age and year of referral effects. The sex ratio
      favored birth-assigned boys at younger ages (3-9 years), but favored birth
      assigned girls at older ages (10-12 years). The percentage of referred birth
      assigned boys significantly decreased when 2 cohorts were compared (2000-2006 vs
      2007-2017). On average, birth-assigned boys were referred at a younger age than
      birth-assigned girls. CLINICAL IMPLICATIONS: The evidence for a change in the sex
      ratio of children referred for gender dysphoria, particularly in recent years,
      matches a similar change in the sex ratio of adolescents referred for gender
      dysphoria. The reasons for this remain understudied. STRENGTH & LIMITATIONS: The
      United Kingdom data showed both similarities and differences when compared to
      data from 2 other gender identity clinics for children (Toronto, Ontario, Canada,
      and Amsterdam, The Netherlands). Such data need to be studied in more gender
      identity clinics for children, perhaps with the establishment of an international
      registry. CONCLUSION: Further study of the correlates of the sex ratio for
      children referred for gender dysphoria will be useful in clinical care and
      management. de Graaf NM, Carmichael P, Steensma TD, et al. Evidence for a Change
      in the Sex Ratio of Children Referred for Gender Dysphoria: Data From the Gender
      Identity Development Service in London (2000-2017). J Sex Med 2018;15:1381-1383.

PMID- 30195564
TI  - Penile Sensory Changes After Plaque Incision and Grafting Surgery for Peyronie's
      Disease.
AB  - INTRODUCTION: Plaque incision and grafting (PIG) for Peyronie's disease (PD) is
      not devoid of complications such as erectile dysfunction and penile sensory
      changes. AIM: To define the rate and chronology of penile sensation loss after
      PIG surgery and to define predictors of such. METHODS: The study population
      consisted of patients with PD-associated penile curvature who underwent PIG
      surgery with at least 6 months of follow-up. Demographics and PD factors were
      recorded. Patient had preoperative assessment of penile sensation and deformity.
      Postoperative follow-up occurred at 1 week, 1 month, 6 months, and 1 year after
      surgery. Neurovascular bundle elevation was conducted with loupe magnification.
      MAIN OUTCOME MEASURE: Penile sensation was evaluated with a biothesiometer and
      graded on a patient-reported visual analog scale (0-10) in which 0 defined a
      completely numb area and 10 defined perfect sensation. The degree of sensation
      loss was defined as extensive (any 1 area >5 cm), major (2-5 cm), and minor (<=2
      cm). The penile sensation loss distribution was defined as focal (1 site) or
      diffuse (>1 site). RESULTS: 63 patients were analyzed. Mean age was 56 +/- 10
      years. Mean duration of PD at the time of PIG was 15 +/- 7 (12-38) months. 75%
      had curvature alone, and 25% had hourglass/indentation deformities. Mean primary
      curvature was 64 +/- 28. The mean operation duration was 3.5 +/- 1.8 hours. 21%
      had some degree of sensation loss at 1 week, 21% at 1 month, 8% at 6 months, and
      3% at 12 months. Only 1 patient (1.5%) at 2 years continued to have extensive
      sensation loss on the glans and distal shaft with a very elevated sensitivity
      threshold. Using multivariable analysis, the only predictor of penile sensation
      loss >=6 months was a duration of operation >4 hours (odds ratio = 2.1; 95%
      confidence interval = 1.2-3.0; P < .01). CLINICAL IMPLICATIONS: The study
      highlights the need during patient consent to discuss penile sensation loss.
      Patients should be informed that rates of penile sensation loss ranges from 2-30%
      and most patients will have complete resolution of any sensation loss within one
      year of follow-up. STRENGTH AND LIMITATIONS: To our knowledge no other studies
      have described the chronology and severity of penile sensation following PIG, our
      study demonstrates the utility of biothesiometry in measuring penile sensation
      before and after PIG. Number of patients and absence of control group represent a
      limitation. CONCLUSION: Sensation loss is not uncommon after PIG surgery. It
      decreases in frequency and severity with time with only rare cases occurring >12
      months. Longer operations appeared to be more likely associated with sensation
      loss. Terrier JE, Tal R, Nelson CJ. Penile sensory changes after plaque incision
      and grafting surgery for Peyronie's disease. J Sex Med 2018;15:1491-1497.

PMID- 30195565
TI  - "I Don't Know What I'm Doing... I Hope I'm Not Just an Idiot": The Need to Train
      Pediatric Urologists to Discuss Sexual and Reproductive Health Care With Young
      Women With Spina Bifida.
AB  - INTRODUCTION: Although pediatric urologists have taken responsibility for
      initiating discussions on sexual and reproductive health with spina bifida
      patients, research shows that very few girls and women with spina bifida have
      ever discussed this topic with any physician. AIM: We sought to better understand
      pediatric urologists' gaps in knowledge and training needs in the sexual and
      reproductive health education of women with spina bifida with the goal of
      creating a tool kit to equip providers to have these discussions. METHODS: In
      this qualitative study, pediatric urologists were interviewed separately about
      their current practices, perceived barriers, knowledge gaps, and recommendations
      for the tool kit until thematic saturation was reached. The interviews were
      recorded and transcribed verbatim, then analyzed using grounded theory by 3
      independent reviewers. MAIN OUTCOME MEASURES: To evaluate the perspectives and
      practices of pediatric urologists, we identified the overlapping themes of the
      interviews. Consensus on themes was reached. RESULTS: 10 Pediatric urologists
      participated in the study, including 5 men and 5 women, of whom 4 were fellows
      and 6 were attending physicians (mean years of practice 18, range 6-31 years).
      The mean number of patients followed up in the respective spina bifida clinics or
      by the provider was 434 (range 24-1,500). The following themes regarding
      pediatric urologists' experience providing sexual and reproductive health
      education to women with spina bifida emerged. Pediatric urologists': (i) lack of
      formal training; (ii) knowledge gaps such as spina bifida sexuality, fertility,
      and pregnancy experience; (iii) barriers to having sexual and reproductive health
      conversations such as lack of comfort and lack of time; (iv) facilitators of
      these conversations such as a long-term relationship with the patient and the
      patient's own initiative; (v) desire to learn and provide competent care; and
      (vi) recommendations for a web-based tool kit that would include content to
      address the knowledge gaps and training about how to start sexual and
      reproductive health conversations. CLINICAL IMPLICATIONS: These findings can
      provide the beginning concepts for the development of training on providing
      sexual and reproductive health education for pediatric urologists' care for women
      with spina bifida. STRENGTHS & LIMITATIONS: This study gives the perspectives of
      10 pediatric urologists with a diversity of backgrounds, but all of whom care for
      a large number of spina bifida patients. This does not give the perspectives of
      the spina bifida women themselves, which will be evaluated in the next phase of
      the study. CONCLUSION: Pediatric urologists are not trained and do not feel
      prepared to provide sexual and reproductive health education for girls and women
      with spina bifida. However, they do see it as their scope of practice and wish to
      acquire competence in this area. Streur CS, Schafer CL, Garcia VP, et al. "I
      Don't Know What I'm Doing... I Hope I'm Not Just an Idiot": The Need to Train
      Pediatric Urologists to Discuss Sexual and Reproductive Health Care With Young
      Women With Spina Bifida. J Sex Med 2018;15:1403-1413.

PMID- 30195566
TI  - Rhodomyrtosone B, a membrane-targeting anti-MRSA natural acylgphloroglucinol from
      Rhodomyrtus tomentosa.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The leaves of Rhodomyrtus tomentosa are
      traditionally used in the treatment of infectious diseases such as wound
      infections in Chinese traditional medicine. The mechanisms of the activity of
      rhodomyrtosone B (RDSB), a natural acylphloroglucinol isolated from the leaves of
      Rhodomyrtus tomentosa, are still not understood. We provided a detailed
      investigation of the antibacterial action of RDSB against bacteria in vitro and
      in vivo. MATERIALS AND METHODS: The antibacterial activity of RDSB was tested by
      the microdilution method against a panel of bacteria, and a time-killing assay
      was carried out according to CLSI guidelines. The cytotoxic potential of RDSB was
      evaluated against mammalian cells, and its haemolytic activity towards rabbit red
      blood cells (RBCs) was assessed. The mode of action of RDSB was investigated by
      targeting bacterial membranes, and its resistance was evaluated using a
      sequential passaging method. The antibacterial activities in vivo were assessed
      against MRSA in a mouse skin infection mode. RESULTS: RDSB exhibited distinct
      antibacterial activities against selected Gram-positive pathogens responsible for
      serious infections, even including methicillin-resistant Staphylococcus aureus
      (MRSA) with a minimum inhibitory concentration (MIC) of 0.62-1.25 ug/mL and
      vancomycin-resistant Enterococcus faecium (VRE) with an MIC of 2.5 ug/mL. RDSB
      displayed much more rapid bactericidal activity against MRSA than that of
      vancomycin. The membrane-targeting experiments revealed that RDSB exhibited
      significant antibacterial activity with the perturbation of bacterial membrane
      potential and an increase in membrane permeability. In particular, RDSB had weak
      cytotoxicity to mammalian cells (IC50 >14 ug/mL) and has advantageous specificity
      against selected Gram-positive bacterial membranes rather than RBCs. Notably,
      RDSB displayed in vitro antibacterial activities against MRSA without drug
      resistance and profoundly attenuated the skin ulcer formation in a murine model
      of MRSA infection under a single dose of 40 ug RDSB per mouse. CONCLUSION: RDSB
      has profound antibacterial activity against drug-resistant bacteria (MRSA and
      VRE) and low cytotoxicity. It is bactericidal in nature, and an increase in
      membrane permeability resulting from membrane perturbation is one of its modes of
      action. RDSB represents a promising natural antibiotic to combat drug-resistant
      (MRSA and VRE) infections.

PMID- 30195567
TI  - Development of an effective and safe topical anti-inflammatory gel containing
      Jatropha gossypiifolia leaf extract: Results from a pre-clinical trial in mice.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Jatropha gossypiifolia L. (Euphorbiaceae) is a
      medicinal plant widely used in traditional medicine as an anti-inflammatory
      remedy. The topical use of the leaves and/or aerial parts of this plant as anti
      inflammatory, analgesic, wound healing and anti-infective in several skin
      diseases is a common practice in many countries. The use of baths or dressings
      with this vegetal species is frequently reported in folk medicine. AIM OF THE
      STUDY: To evaluate the topical anti-inflammatory of aqueous extract from leaves
      of J. gossypiifolia and to develop a safe and effective herbal gel with anti
      inflammatory potential. MATERIAL AND METHODS: First, the topical acute anti
      inflammatory activity of J. gossypiifolia extract was evaluated in ear edema
      induced by single application of croton oil in mice. Then, a polaxamer-based gel
      containing J. gossypiifolia extract was developed, physicochemically
      characterized and evaluated in the same model of inflammation to assess whether
      the extract incorporation in gel would affect its anti-inflammatory potential.
      The best formulation was then assayed in ear edema induced by multiple
      applications of croton oil in mice, to evaluate its chronic anti-inflammatory
      potential. Inflammatory parameters evaluated included edema, nitrite
      concentration, mieloperoxidase (MPO) activity and oxidative damage in lipids and
      proteins. Finally, dermal irritation/corrosion test in mice was performed to
      access the safeness of the developed gel. Phytochemical characterization of J.
      gossypiifolia extract was performed by high performance liquid chromatography
      with diode array detector (HPLC-DAD) analysis. RESULTS: J. gossypiifolia showed
      significant acute anti-inflammatory activity in ear edema model, and this
      activity was significantly increased when equivalent amounts of extract was
      applied incorporated in the developed polaxamer gels. The gels containing
      different amounts of extract reduced significantly the levels of edema, nitrite
      and MPO enzyme in mice ears, with intensity similar to the anti-inflammatory
      standard drug dexamethasone. The gel containing 1.0% of extract was further
      evaluated and also showed significant anti-inflammatory activity in chronic
      inflammation test, reducing significantly ear edema, lipid peroxidation and
      depletion of reduced glutathione, similarly to dexamethasone. Placebo formulation
      as well as gel containing extract showed pH compatible to that of human skin and
      exhibited absence of signs of toxicity in mice, indicating the safeness of the
      developed product for topical use. HPLC analysis confirmed the presence of C
      glycosylflavonoids (orientin, isoorientin, vitexin and isovitexin) as the major
      compounds of J. gossypiifolia aqueous leaf extract. CONCLUSIONS: The results
      demonstrate the potentiality of J. gossypiifolia gel as a promising safe and
      effective topical anti-inflammatory agent for treatment of cutaneous inflammatory
      diseases.

PMID- 30195568
TI  - Dragon's Blood exerts cardio-protection against myocardial injury through PI3K
      AKT-mTOR signaling pathway in acute myocardial infarction mice model.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Dragon's Blood (DB), the red resin of Dracaena
      cochinchinensis (Lour.) S. C., has been used in traditional Chinese medicine to
      treat acute myocardial infarction (AMI) for centuries. Evidence indicated that DB
      may exert cardio-protective effect by inhibiting inflammatory response during
      myocardial infarction. However, its pharmaceutical mechanism is still to be
      elucidated. AIM OF THE STUDY: Due to its potential anti-inflammatory effect,
      Dragon's Blood extract (DBE) was applied on AMI mice model in this study and its
      mechanism on inflammation via PI3K-AKT-mTOR signaling pathway was to be
      validated. MATERIALS AND METHODS: AMI mice model was established by ligation of
      left anterior descending (LAD) arteries. DBE was administered for 7 days before
      the surgery. Heart function was evaluated by 2D echocardiography. Levels of CK-MB
      and LDH1 in serum as well as TXB2, 6-keto-PGF1alpha and ET-1 in plasma were
      detected. Level of IL-6 in cardiac tissues was quantified by ELISA. Expressions
      of key proteins in PI3K-AKT-mTOR signaling pathway were detected by Western blot.
      RESULTS: The result demonstrated that DBE could improve heart function in AMI
      mice model. Meanwhile, it could also regulate levels of CK-MB and LDH1, and
      restore balance between TXB2 and 6-keto-PGF1alpha. Further study suggested that
      DBE could inhibit inflammation and regulate expressions of key proteins in IL-6
      JAK2/STAT3 pathway in cardiac tissue. Western blot results validated that DBE
      could activate PI3K-AKT-mTOR signaling pathway, thereby regulating the
      expressions of its downstream targets, including VEGF, COX2 and PPARgamma.
      CONCLUSION: DBE exerts cardio-protective efficacy by activating JAK2-STAT3 and
      PI3K-AKT-mTOR pathways in cardiac tissue. These findings provide insight into the
      pharmacological mechanism of DBE and validate the beneficial effects of DBE in
      the clinical application for AMI.

PMID- 30195569
TI  - Mucosal immunomodulatory evaluation and chemical profile elucidation of a
      classical traditional Chinese formula, Bu-Zhong-Yi-Qi-Tang.
AB  - ETHNOPHARMACOLOGICAL EVIDENCE: With fast development and high pace life in modern
      society, autoimmune diseases like inflammatory bowel disease had become
      increasingly common. Bu-Zhong-Yi-Qi-Tang (BZYQT), a famous traditional Chinese
      medicine prescription (TCMP), has been used for 700 years mainly in Eastern Asia
      countries for the treatment of gastrointestinal and respiratory disorder, and
      weakness after serious diseases. These diseases were proved to be closely related
      to human immune system, among which, mucosal immune system is the largest immune
      system. So it is necessary to discover the mucosal immune related bioactive
      components of BZYQT. AIM OF THE STUDY: To evaluate the mucosal immunomodulatory
      bioactivity of BZYQT and ingredients. MATERIALS AND METHODS: Peyer's patches were
      collected from mice administrated orally with BZYQT, its related Octadecylsilane
      (ODS) fractions and polysaccharide part. Productions of several cytokines
      including IL-2, IL-4, IL-5, and IFN-gamma from T lymphocytes were tested with
      enzyme linked immunosorbent assay (ELISA) by Peyer's patch cells ex vivo
      experiments. Chemical profile including low molecular part and polysaccharide
      part were investigated. Low molecular part of BZYQT and related ODS fractions
      were analyzed by ultra-performance liquid chromatography coupled with quadrupole
      time-of-flight tandem mass spectrometry (UPLC-Q/TOF-MS) based on LC-MS
      information from self-established compound library. exclusion chromatography, and
      chemical property has been analyzed. RESULT: Three-days' administration of BZYQT
      enhanced productions of IL-4 and IFN-gamma in T lymphocytes of Peyer's patches in
      addition to IL-2. Some hydrophobic low molecular weight fractions (30%, 70% and
      100% MeOH ODS fraction), which were fractionated from BZYQT by ODS column
      chromatography, showed enhancing or suppressive effects on productions of IL-2,
      IL-4 or IL-5 in T lymphocytes of Peyer's patches after oral administration.
      Besides, 161 components from hydrophobic low molecular weight fractions of BZYQT
      were unequivocally identified or tentatively characterized by UPLC-Q/TOF-MS
      according to retention time behaviors and fragments, and most of them were
      flavonoids and saponins from Glycyrrhizae Radix, Citri Reticulatae Pericarpium,
      and Cimicifugae Rhizoma. Polysaccharide part was separated and purified both by
      anion-exchange and size. BZYQT also contained at least one neutral and three
      weakly or strongly acidic polysaccharides, and analysis of their chemical
      properties indicated that a neutral polysaccharide was glucan, and acidic
      polysaccharides possessed heteroglycan and pectic arabinogalactan features.
      Murine administration of polysaccharide fractions of BZYQT induced different
      changes on functions of T lymphocytes in Peyer's patches from hydrophobic low
      molecular weight fractions. By experiment using intranasally-immunized mice,
      BZYQT negatively regulated antibody response in lung as combinatorial actions of
      its low molecular weight ingredients and polysaccharides. CONCLUSION: BZYQT
      contains several low and macromolecular weight ingredients, which affect to
      immune-function of T lymphocytes in Peyer's patches, and the formula expresses
      its regulative activity on lower respiratory immune system through combinatorial
      actions of these ingredients on immunocompetent cells in Peyer's patches.

PMID- 30195570
TI  - Lightening Becker's nevus: Role of topical therapies.

PMID- 30195571
TI  - Tofacitinib for the treatment of alopecia areata in preadolescent children.

PMID- 30195572
TI  - Ruxolitinib for the treatment of severe alopecia areata.

PMID- 30195573
TI  - Reply to MS#JAAD-D-18-01527.

PMID- 30195574
TI  - Trichloroacetic acid as a treatment for persistent oral mucosal lesions in
      pemphigus vulgaris.

PMID- 30195575
TI  - Live fast, die young? A review on the developmental trajectories of ADHD across
      the lifespan.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is highly heritable and the most
      common neurodevelopmental disorder in childhood. In recent decades, it has been
      appreciated that in a substantial number of cases the disorder does not remit in
      puberty, but persists into adulthood. Both in childhood and adulthood, ADHD is
      characterised by substantial comorbidity including substance use, depression,
      anxiety, and accidents. However, course and symptoms of the disorder and the
      comorbidities may fluctuate and change over time, and even age of onset in
      childhood has recently been questioned. Available evidence to date is poor and
      largely inconsistent with regard to the predictors of persistence versus
      remittance. Likewise, the development of comorbid disorders cannot be foreseen
      early on, hampering preventive measures. These facts call for a lifespan
      perspective on ADHD from childhood to old age. In this selective review, we
      summarise current knowledge of the long-term course of ADHD, with an emphasis on
      clinical symptom and cognitive trajectories, treatment effects over the lifespan,
      and the development of comorbidities. Also, we summarise current knowledge and
      important unresolved issues on biological factors underlying different ADHD
      trajectories. We conclude that a severe lack of knowledge on lifespan aspects in
      ADHD still exists for nearly every aspect reviewed. We encourage large-scale
      research efforts to overcome those knowledge gaps through appropriately granular
      longitudinal studies.

PMID- 30195577
TI  - Dietary intake of flavonoid subclasses and risk of type 2 diabetes in prospective
      cohort studies: A dose-response meta-analysis.
AB  - Flavonoids intake has been linked to risk of type 2 diabetes theoretically, but
      the findings were conflicting from observational studies. Results from the recent
      meta-analysis suggested a moderate favorable effect of total dietary flavonoids
      consumption on type 2 diabetes risk. However, the relationship, if exists,
      between total dietary flavonoids consumption and type 2 diabetes risk is unclear,
      especially further in the association between flavonoid subclasses and risk of
      type 2 diabetes. Thus, the dose-response relationship was assessed by restricted
      cubic spline model and multivariate random-effect meta-regression. Among
      flavonoid subclasses, protective effects were obtained for intakes of flavonols,
      flavan-3-ols, isoflavones and anthocyanidins in high vs. low analysis and dose
      response analysis.

PMID- 30195576
TI  - Accuracy of blinded clinician interpretation of single-lead smartphone
      electrocardiograms and a proposed clinical workflow.
AB  - Despite the appeal of smartphone-based electrocardiograms (ECGs) for arrhythmia
      screening, a paucity of data exists on the accuracy of primary care physicians'
      and cardiologists' interpretation of tracings compared with the device's
      automated diagnosis. Using 408 ECGs in 51 patients, we demonstrate a variable
      accuracy in clinician interpretation of smartphone-based ECGs, with only
      cardiologists demonstrating satisfactory agreement when referenced against a 12
      lead ECG. Combining the device automated diagnostic algorithm with cardiologist
      interpretation of only uninterpretable traces yielded excellent results and
      provides an efficient, cost-effective workflow for the utilization of a
      smartphone-based ECG in clinical practice.

PMID- 30195578
TI  - Metabolic healthy overweight/obese individuals: Not just a restricted group.

PMID- 30195580
TI  - Pimp My Ribosome: Ribosomal Protein Paralogs Specify Translational Control.
AB  - The ability of cells to grow and divide, differentiate and function, and even
      senesce is dependent on the fine-tuning of both gene and protein expression.
      Protein concentration in the cell is regulated not only at the transcriptional
      and post-translational levels, but also at the level of translation. Ribosomes,
      the molecular machines behind translation, were once considered to be an
      invariant driving force behind protein expression. However, studies over the past
      decade paint a rather different picture; namely, that ribosomes constitute an
      additional layer of regulatory control that might define which subsets of mRNAs
      are translated, to what extent, and to what purpose. Recent works summarized
      herein directly implicate ribosome heterogeneity and, in particular, ribosomal
      protein (RP) paralog specificity in regulating mRNA translation and control of
      the cellular translatome.

PMID- 30195579
TI  - Measuring defibrillator surface potentials: The validation of a predictive
      defibrillation computer model.
AB  - Implantable cardioverter defibrillators (ICDs) are commonly used to reduce the
      risk in patients with life-threatening arrhythmias, however, clinicians have
      little systematic guidance to place the device, especially in cases of unusual
      anatomy. We have previously developed a computational model that evaluates the
      efficacy of a delivered shock as a clinical and research aid to guide ICD
      placement on a patient specific basis. We report here on progress to validate
      this model with measured ICD surface potential maps from patients undergoing ICD
      implantation and testing for defibrillation threshold (DFT). We obtained body
      surface potential maps of the defibrillation pulses by adapting a limited lead
      selection and potential estimation algorithm to deal with the limited space for
      recording electrodes. Comparison of the simulated and measured potential maps of
      the defibrillation shock yielded similar patterns, a typical correlation greater
      than 0.9, and a relative error less than 15%. Comparison of defibrillation
      thresholds also showed accurate prediction of the simulations. The high agreement
      of the potential maps and DFTs suggests that the predictive simulation generates
      realistic potential values and can accurately predict DFTs in patients. These
      validation results pave the way for use of this model in optimization studies
      prior to device implantation.

PMID- 30195582
TI  - Integration of cardiac energetics, function and histology from isolated rat
      hearts perfused with doxorubicin and doxorubicin-ol; a model for use in drug
      safety evaluations.
AB  - The isolated rat heart (Langendorff) assay combined with NMR spectroscopy and
      histology were used to elucidate functional, metabolic, and histological signs of
      cardiotoxicity resulting from acute exposure to clinically relevant
      concentrations of doxorubicin and its metabolite dox-ol. Doxorubicin blood
      concentrations and pharmacokinetic parameters were assessed following a
      clinically relevant dose of 2 mg/kg in order to select concentrations for
      isolated heart perfusions. Isolated rat hearts were exposed to 1 or 10 MUM of
      doxorubicin or 0.3 MUM dox-ol for at least 60 min using the Langendorff perfusion
      method. Effects on heart function were monitored using ECGs, left ventricular
      contraction parameters, and microscopic histology. Cardiac energetics (PCr, ATP,
      and Pi) were evaluated before, during, and after exposure to doxorubicin/dox-ol
      in perfused hearts using NMR spectroscopy. Cardiac effects were evident following
      clinically relevant concentrations of doxorubicin and dox-ol in isolated rat
      hearts demonstrated by altered heart function, energetic reserve, and microscopic
      lesions. A cardiac stress test utilizing isoproterenol resulted in enhanced
      functional response and reductions in PCr in doxorubicin versus vehicle treated
      hearts indicating possible alterations in the isoproterenol mediated pathway. Dox
      ol treated hearts were similar to control with regard to function, but exhibited
      histologic findings. The use of combined Langendorff/NMR/histology methodologies
      allowed for comparison of multiple indices of cardiac function at one time in
      which cardiac effects were evident in multiple parameters. SHORT ABSTRACT: The
      isolated rat heart assay combined with NMR spectroscopy and histology was used to
      elucidate functional, metabolic, and histological signs of cardiotoxicity
      resulting from acute exposure to clinically relevant concentrations of
      doxorubicin and its metabolite dox-ol. Heart function was altered and microscopic
      signs of toxicity were evident with dox and dox-ol exposures. The use of combined
      Langendorff/NMR/histology assays allowed for comparison of multiple indices of
      cardiac function at one time in which cardiac effects were evident in multiple
      parameters.

PMID- 30195581
TI  - Transposons, p53 and Genome Security.
AB  - p53, the most commonly mutated tumor suppressor, is a transcription factor known
      to regulate proliferation, senescence, and apoptosis. Compelling studies have
      found that p53 may prevent oncogenesis through effectors that are unrelated to
      these canonical processes and recent findings have uncovered ancient roles for
      p53 in the containment of mobile elements. Together, these developments raise the
      possibility that some p53-driven cancers could result from unrestrained
      transposons. Here, we explore evidence linking conserved features of p53 biology
      to the control of transposons. We also show how p53-deficient cells can be
      exploited to probe the behavior of transposons and illustrate how unrestrained
      transposons incited by p53 loss might contribute to human malignancies.

PMID- 30195583
TI  - Short-term outcome of first episode delusional disorder in an early intervention
      population.
AB  - BACKGROUND: Previous evidence suggests that delusional disorder has a later onset
      and better functional outcomes compared to schizophrenia. However, studies have
      not examined longitudinal outcomes in a first episode population, where
      confounding factors may be adjusted for. METHODS: A nested case control study was
      designed within the National EDEN study; a cohort of 1027 first episode psychosis
      patients. Patients with a baseline diagnosis of delusional disorder (n = 48) were
      compared with schizophrenia (n = 262) at 6 and 12 months with respect to
      symptomatic and functional outcomes. Regression analysis was used to adjust for
      possible confounders. RESULTS: Delusional disorder patients had a shorter
      duration of untreated psychosis compared to schizophrenia but were similar in
      other baseline characteristics. At baseline, delusional disorder patients had
      lower symptom scores but higher function scores compared to those with
      schizophrenia. At 12 months the differences persisted for symptoms scores but not
      overall function scores. After adjusting for baseline score, age and duration of
      untreated psychosis, differences between the groups remained significant only for
      Positive and Negative Syndrome Scale (PANNS) negative, general and total scores
      and recovery rates. There were no differences in changes in outcomes scores.
      CONCLUSIONS: Delusional disorder in a first episode psychosis population presents
      with less severe symptoms, higher recovery rates and better functioning than
      schizophrenia, but at 12 months differences are ameliorated when adjusting for
      baseline differences.

PMID- 30195584
TI  - [Contiguous cutaneous inflammation: Different scenarios, unclear outlines].

PMID- 30195585
TI  - Predicting the Response to Cardiac Rehabilitation: Identifying the Right
      Ventricular Predictor of Oxygen Uptake Improvement in Heart Failure Patients.

PMID- 30195586
TI  - Circulating microRNAs as biomarkers in traumatic brain injury.
AB  - Preclinical and clinical studies can be greatly improved through the inclusion of
      diagnostic, prognostic, predictive or pharmacodynamics biomarkers. Circulating
      microRNAs (miRNAs) represent highly stable targets that respond to physiological
      and pathological changes. MicroRNA biomarkers can be detected by highly sensitive
      and absolutely quantitative methods currently available in most clinical
      laboratories. Here we review preclinical and clinical studies that have examined
      circulating miRNAs as potential diagnostic and prognostic biomarkers. We also
      present data that suggests pharmacodynamics biomarkers can be identified that are
      associated with neuroprotection in general. Although circulating miRNA can serve
      as useful tools, it is clear their expression profiles are highly sensitive to
      changing conditions and are influenced by a broad range of parameters including
      age, sex, body mass index, injury severity, time of collection, as well as
      methods of processing, purification and detection. Thus, considerable effort will
      be required to standardize methods and experimental design conditions before
      circulating miRNAs can prove useful in a heterologous injury like TBI.

PMID- 30195587
TI  - Conditioned gaping produced by high dose Delta9-tetrahydracannabinol:
      Dysregulation of the hypothalamic endocannabinoid system.
AB  - Delta9-tetrahydracannabinol (THC) is recognized as an effective treatment for
      nausea and vomiting via its action on the cannabinoid 1 (CB1) receptor.
      Paradoxically, there is evidence that THC can also produce nausea and vomiting.
      Using the conditioned gaping model of nausea in rats, we evaluated the ability of
      several doses of THC (0.0, 0.5, 5 and 10 mg/kg, i.p.) to produced conditioned
      gaping reactions. We then investigated the ability of the CB1 receptor
      antagonist, rimonabant, to block the establishment of THC-induced conditioned
      gaping. Real-time polymerase chain reaction (RT-PCR) was then used to investigate
      changes in endocannabinoid related genes in various brain regions in rats
      chronically treated with vehicle (VEH), 0.5 or 10 mg/kg THC. THC produced dose
      dependent gaping, with 5 and 10 mg/kg producing significantly more gaping
      reactions than VEH or 0.5 mg/kg THC, a dose known to have anti-emetic properties.
      Pre-treatment with rimonabant reversed this effect, indicating that THC-induced
      conditioned gaping was CB1 receptor mediated. The RT-PCR analysis revealed an
      upregulation of genes for the degrading enzyme, monoacylglycerol lipase (MAGL),
      of the endocannabinoid, 2-arachidolyl glycerol (2-AG), in the hypothalamus of
      rats treated with 10 mg/kg THC. No changes in the expression of relevant genes
      were found in nausea (interoceptive insular cortex) or vomiting (dorsal vagal
      complex) related brain regions. These findings support the hypothesis that THC
      induced nausea is a result of a dysregulated hypothalamic-pituitary-adrenal axis
      leading to an overactive stress response.

PMID- 30195588
TI  - Development of a saphenous vein harvest model for simulation-based assessment.
AB  - OBJECTIVE: There is a need to develop a realistic model of open saphenous vein
      harvesting for simulation training and assessment. The purpose of this study was
      to develop a novel simulated model of this procedure and to examine its viability
      by examining participants' performance and feedback on this model. METHODS: A
      total of 14 participants (cardiac surgeons, residents, students) conducted open
      saphenous vein harvesting on a portable, noncommercial, simulated vein model
      (complete with artificial vein, subcutaneous tissue, and skin) within an
      operating room. Surgical assistance was provided by a cardiac resident.
      Participants provided feedback through questionnaires and interviews. Technical
      performance was rated by 2 blinded raters using a global rating scale for
      operative technical skills. RESULTS: Quantitative analyses demonstrated that
      participants considered the model to be realistic and useful. Analyses of
      performance ratings indicated that the model could be used as a reliable
      indicator of skill level, given that raters were able to use performance scores
      to discriminate participants according to their level of experience at a high
      level of accuracy. Participants with a higher level of experience performed
      significantly better than those with a lower level of experience. Qualitative
      analyses revealed the model was considered to be most beneficial to learn
      procedural steps of vein harvesting and basic surgical skills. CONCLUSIONS:
      Results provide support for the technical fidelity of this model and its ability
      to identify skill level for assessment of vein harvesting. Future work should
      examine transfer of surgical skills from simulator to clinical practice to assess
      its viability for training.

PMID- 30195589
TI  - Poorer sleep quality among adult patients with pectus excavatum in Taiwan: A
      pilot study.
AB  - OBJECTIVES: Patients with pectus excavatum have a poorer quality of life than the
      general population. Sleep quality is a critical component of quality of life.
      This pilot study compared the sleep quality of adult patients with pectus
      excavatum with that of the general population in Taiwan. METHODS: Participants
      comprised 30 healthy adults, 21 adult outpatients with pectus excavatum, and 33
      adults with pectus excavatum receiving Nuss surgery. The Pittsburgh Sleep Quality
      Index measured subjective sleep quality; the Visual Analog Scale for Pain, Brief
      Symptom Rating Scale-5, Beck Depression Inventory II, and 36-Item Short Form
      Survey measured quality of life; and the Epworth Sleepiness Scale measured
      excessive daytime sleepiness. Outcome measurements were obtained at baseline for
      all groups and 6 months after Nuss surgery for inpatients. RESULTS: Patients with
      pectus excavatum had poorer sleep quality and worse quality of life than
      controls. Poorer sleep quality was not related to the severity of pectus
      excavatum per se, but to psychologic issues (beta = 0.18, P < .001 in multiple
      linear regression analysis). Measurement time had no effect on sleep quality
      (beta = 0.31, P = .594 for outpatient group; beta = 0.27, P = .665 for
      inpatients). Sleep quality of patients with pectus excavatum improved after Nuss
      surgery (Pittsburgh Sleep Quality Index: 4 vs 7, P = .002). CONCLUSIONS: Our
      findings suggested an association between poor sleep quality and pectus
      excavatum; thus, sleep quality should be evaluated before and after the Nuss
      procedure.

PMID- 30195590
TI  - Transaortic transcatheter aortic valve implantation: A route to be protected and
      not neglected.

PMID- 30195592
TI  - Discovery of biomarkers that diagnose kidney disease progression and novel
      patient management strategies needed now to prevent progressive kidney disease.

PMID- 30195591
TI  - A novel role of endothelial autophagy as a regulator of myocardial fatty acid
      oxidation.
AB  - BACKGROUND: We sought to determine if endothelial autophagy affects myocardial
      energy metabolism. METHODS: We used isolated working mouse hearts to compare
      cardiac function, energy metabolism, and ischemic response of hearts from
      endothelial cell-specific ATG7 knockout (EC-ATG7-/-) mice to hearts from their
      wild-type littermates. We also conducted gene analyses on human umbilical vein
      endothelial cells incubated with scrambled small interfering RNA or small
      interfering ATG7. RESULTS: In the presence of insulin, working hearts from EC
      ATG7-/- mice, relative to those from wild-type littermates, exhibited greater
      reductions in insulin-associated palmitate oxidation indicating a diminished
      reliance on fatty acids as a fuel source. Likewise, palmitate oxidation was
      markedly lower in the hearts of EC-ATG7-/- mice versus wild-type mice during
      reperfusion of ischemic hearts. Although hearts from EC-ATG7-/- mice revealed
      significantly lower triacylglycerol content compared with those from wild-type
      mice, ATG7-silenced human umbilical vein endothelial cells demonstrated
      appreciably lower fatty acid binding protein 4 and 5 expression relative to those
      treated with scrambled small interfering RNA. CONCLUSIONS: Disruption of
      endothelial autophagy reduces cardiac fatty acid storage and dampens reliance on
      fatty acid oxidation as a cardiac fuel source. The autophagy network represents a
      novel target for designing new strategies aimed at resetting perturbed myocardial
      bioenergetics.

PMID- 30195593
TI  - Early intraoperative iron-binding proteins are associated with acute kidney
      injury after cardiac surgery.
AB  - OBJECTIVES: Iron regulation is an important modifier of renal ischemia
      reperfusion injury, but the role of iron-binding proteins during cardiopulmonary
      bypass remains unclear. The goal was to characterize iron-binding proteins
      throughout ischemia-reperfusion injury to determine their association with acute
      kidney injury development. METHODS: A prospective observational cohort of adult
      patients who underwent cardiac surgery (n = 301) was obtained, and acute kidney
      injury was defined by Kidney Disease Improving Global Outcomes. Serum ferritin,
      transferrin saturation, and urine hepcidin-25 were measured. RESULTS:
      Intraoperative serum ferritin was lower at the start of cardiopulmonary bypass (P
      = .005) and 1-hour cardiopulmonary bypass (P = .001) in patients with acute
      kidney injury versus patients without acute kidney injury. Lower serum ferritin
      and higher transferrin saturation at 1-hour cardiopulmonary bypass were
      independent predictors of acute kidney injury (serum ferritin odds ratio, 0.66;
      95% confidence interval [CI], 0.48-0.91; transferrin saturation odds ratio, 1.26;
      95% CI, 1.02-1.55) and improved model discrimination (area under the curve [AUC],
      0.76; 95% CI, 0.67-0.85) compared with clinical prediction alone (AUC, 0.72; 95%
      CI, 0.62-0.81; DeltaAUC and net reclassification index, P = .01). Lower ferritin,
      higher transferrin saturation at 1-hour cardiopulmonary bypass, and lower urine
      hepcidin-25 at postoperative day 1 were also independent predictors for acute
      kidney injury development, and this model demonstrated an AUC of 0.80 (0.72
      0.87), which was superior to clinical prediction (DeltaAUC P = .002, integrated
      discrimination improvement and net reclassification index P = .003). CONCLUSIONS:
      Our findings suggest that lower levels of intraoperative iron-binding proteins
      may reflect an impaired capacity to rapidly handle catalytic iron released during
      cardiopulmonary bypass, leading to kidney injury. These data highlight the
      importance of iron homeostasis in human ischemia-reperfusion injury and suggest
      it is a potentially modifiable risk during cardiac surgery. Intraoperative
      detection of incipient acute kidney injury may be feasible and could be used as
      an enrichment strategy for clinical trials.

PMID- 30195594
TI  - Simulation: Are we there yet?

PMID- 30195595
TI  - Replacement of the aortic root: Does only size matter?

PMID- 30195596
TI  - Tearing it up: Addressing the septum during endovascular repair of chronic distal
      aortic dissections.

PMID- 30195597
TI  - Comparing apples with oranges: The funfair of statistics.

PMID- 30195598
TI  - Evaluation of the real-world impact of rotational thromboelastometry-guided
      transfusion protocol in patients undergoing proximal aortic surgery.
AB  - BACKGROUND: Complex aortic procedures are potentially associated with important
      blood loss and coagulopathy. The aim of this study was to assess the impact of
      rotational thromboelastometry (ROTEM, Tem International GmBH, Munich, Germany) on
      transfusion requirements after proximal aortic operations in a real-world
      setting. METHODS: This single-center retrospective analysis based on 385
      consecutive patients undergoing cardiac surgeries involving the aortic root,
      ascending aorta, or aortic arch compared 197 controls managed according to
      routine transfusion protocol before the introduction of the ROTEM in 2012 with
      188 patients operated afterward. With the use of a 1:1 propensity score match,
      224 patients were included in paired analysis (112 in each group). The primary
      end point was erythrocytes transfusion rate. The secondary end points comprised
      the transfusion of other allogeneic blood products, number of units transfused,
      postoperative blood loss, massive transfusion rate, and use of other hemostatic
      products. RESULTS: ROTEM implementation was associated with a trend toward
      reduction in the rate of erythrocytes transfusion (57% vs 46%, P = .08) and a
      decreased median number of units transfused for erythrocytes (1.0 [0.0-4.0] unit
      vs 0.0 [0.0-2.0] unit, P = .03) and plasma (0.0 [0.0-4.0] unit vs 0.0 [0.0-2.0]
      unit, P = .04). After sensitivity analysis, ROTEM displayed a comparable rate of
      erythrocytes transfusion (58% vs 47%, P = .15). CONCLUSIONS: In a real-world
      setting, ROTEM-based algorithm implementation could help reduce excess
      erythrocytes transfusion for complex aortic procedures. We advocate for a strict
      adherence and concerted team effort to maximize the benefits of such addition to
      patients' management.

PMID- 30195599
TI  - Hemostatic patch for coronary sinus rupture: An efficient solution for a
      complicated problem?

PMID- 30195600
TI  - Estimating postoperative left ventricular volume: Identification of responders to
      surgical ventricular reconstruction.
AB  - OBJECTIVES: The postoperative left ventricular end-systolic volume index and
      ejection fraction are benchmarks of surgical ventricular reconstruction but
      remain unpredictable. This study aimed to identify who could be associated with a
      higher long-term survival by adding surgical ventricular reconstruction to
      coronary artery bypass grafting than coronary artery bypass grafting alone
      (responders to surgical ventricular reconstruction). METHODS: The subjects were
      293 patients (median age, 63 years; 255 men) who underwent coronary artery bypass
      grafting for ischemic heart disease with left ventricular dysfunction in 16
      cardiovascular centers in Japan. The relationships among surgical ventricular
      reconstruction, postoperative end-systolic volume index, ejection fraction, and
      survival were analyzed to identify responders to surgical ventricular
      reconstruction. RESULTS: Surgical ventricular reconstruction was performed in 165
      patients (56%). The end-systolic volume index and ejection fraction significantly
      improved (end-systolic volume index, 91 to 64 mL/m2; ejection fraction, 28% to
      35%) for all patients. The postoperative end-systolic volume index and ejection
      fraction were estimated, and surgical ventricular reconstruction was found to be
      significantly associated with both end-systolic volume index (14.5 mL/m2
      reduction, P < .001) and ejection fraction (3.1% increase, P = .003). During the
      median follow-up of 6.8 years, 69 patients (24%) died. Only the postoperative
      ejection fraction was significantly associated with survival (hazard ratio,
      0.925; 95% confidence interval, 0.885-0.968), although this effect was limited to
      those with postoperative end-systolic volume index of 40 to 80 mL/m2 in the
      subgroup analysis (hazard ratio, 0.932; 95% confidence interval, 0.894-0.973).
      CONCLUSIONS: Adding surgical ventricular reconstruction to coronary artery bypass
      grafting could reduce the mortality risk by increasing ejection fraction for
      those with a postoperative end-systolic volume index within a specific range. The
      postoperative end-systolic volume index could demarcate responders to surgical
      ventricular reconstruction, and its estimation can help in surgical decision
      making.

PMID- 30195601
TI  - Pain after posterolateral versus nerve-sparing thoracotomy: A randomized trial.
AB  - OBJECTIVES: Post-thoracotomy pain leads to patient discomfort, pulmonary
      complications, and increased analgesic use. Intercostal nerve injury during
      thoracotomy or its entrapment during closure can contribute to post-thoracotomy
      pain. We hypothesized that a modified technique of posterolateral thoracotomy and
      closure, preserving the intercostal neurovascular bundle, would reduce acute and
      chronic post-thoracotomy pain. METHODS: We randomized 90 patients undergoing
      posterolateral thoracotomy for pulmonary resection at a tertiary level oncology
      center to standard posterolateral (control arm) or modified nerve-sparing
      thoracotomy. All patients received morphine via patient-controlled analgesia
      pumps. The primary outcome was the worst postoperative pain score in the first 3
      postoperative days. Secondary outcomes included the average pain score and
      analgesic requirements in the first 3 postoperative days and the incidence of
      post-thoracotomy pain 6 months after surgery. RESULTS: No significant differences
      were seen between the groups in acute or chronic post-thoracotomy measured by the
      numeric rating scale. There was no difference seen in the worst (mean)
      postoperative pain scores (3.71 vs 3.83, difference 0.12; 99% confidence interval
      [CI], -0.7 to +0.9; P = .7), average (mean) pain scores in the first 3
      postoperative days (1.77 vs 1.85, difference 0.08; 99% CI, -0.4 to +0.6; P =
      .69), mean consumption of morphine (mg/kg) (1.45 vs 1.40, difference -0.05; 99%
      CI, -0.4 to +0.3; P = .73), or incidence of chronic postoperative pain (37.8% vs
      40%, difference 4.9%; 99% CI, -22.8 to +30.7%; P = .73). CONCLUSIONS: The
      modified nerve-sparing thoracotomy technique does not reduce post-thoracotomy
      pain compared with standard posterolateral thoracotomy.

PMID- 30195602
TI  - Rene Favaloro and the fatherhood of the coronary bypass operation: Lest we
      forget.

PMID- 30195603
TI  - Inhibiting a spinal cord signaling pathway protects against ischemia injury in
      rats.
AB  - OBJECTIVE: The aim of the study was to examine whether the cannabinoid agonist
      WIN55212-2 could attenuate ischemic spinal cord injury (SCI) in rats through
      inhibition of GAPDH/Siah1 signaling. METHODS: Male Sprague-Dawley rats were
      distributed randomly into 5 groups: (1) sham group that received no aortic
      occlusion and injected intraperitoneally (i.p.) with vehicle control after
      reperfusion; (2) control group that received a 12-minute aortic occlusion and
      injected i.p. with vehicle control after reperfusion; (3) WIN55212-2 group (WIN)
      that received the aortic occlusion and injected i.p. with 1 mg/kg of WIN55212-2
      after reperfusion; and (4) WIN55212-2 plus AM251 group and (5) WIN55212-2 plus
      AM630 group that received the same surgical operation as the WIN group, except
      that 1 mg/kg of AM251 or AM630 was injected i.p. 30 min before each dose of
      WIN55212-2 injection, respectively. Neurologic function was assessed 48 hours
      after reperfusion. Histopathologic examination was performed to determine the
      number of normal neurons in anterior spinal cord. Protein expression of active
      caspase-3, total caspase-3, glyceraldehyde 3-phosphate dehydrogenase (GAPDH),
      inducible nitric oxide synthase (iNOS), nuclear factor kappa light chain enhancer
      of activated B cells (NF-kappaB), Siah1, tumor necrosis factor alpha, and
      interleukin 1beta were determined with Western blot and enzyme-linked
      immunosorbent assay; coimmunoprecipitation assays were also used to determine
      GAPDH/Siah1 complexing. Finally, terminal deoxynucleotidyl transferase dUTP nick
      end labeling staining was used to determine neuronal apoptosis in the lumbar
      spinal cord. RESULTS: The nuclear translocation of GAPDH and Siah1 in the spinal
      cord was initiated after ischemic spinal cord injury (SCI) along with the
      increased formation of GAPDH/Siah1 complexes. However, the activation of
      GAPDH/Siah1 was blocked by WIN. In addition, the treatment of WIN55212-2 promoted
      neuronal survival in the spinal cord, reduced apoptosis and inflammation, and
      improved neurologic scores. Furthermore, these beneficial effects of WIN55212-2
      were abolished by the combined treatment of the CB2 antagonist AM630, but not the
      CB1 antagonist AM251. CONCLUSIONS: Our findings reveal GAPDH/Siah1 signaling
      cascades as a novel therapeutic target for ischemic SCI and identify WIN55212-2
      with the potential to treat ischemic SCI by targeting this pathway.

PMID- 30195604
TI  - Prediction of postoperative lung function after major lung resection for lung
      cancer using volumetric computed tomography.
AB  - OBJECTIVES: The study objectives were to assess the accuracy of volumetric
      computed tomography to predict postoperative lung function in patients with lung
      cancer in relation to anatomic segments counting and perfusion scintigraphy, to
      generate specific predictive equations for each functional parameter, and to
      evaluate accuracy and precision of these in a validation cohort. METHODS: We
      assessed pulmonary functions preoperatively and 3 to 4 months postoperatively
      after lung resection for lung cancer (n = 114). Absolute and relative lung
      volumes (total and upper/middle/lower) were determined using volumetric software
      analysis for staging thoracic computed tomography scans. Predicted postoperative
      function was calculated by segments counting, scintigraphy, and volumetric
      computed tomography. RESULTS: Volumetric computed tomography achieves a higher
      correlation and precision with measured postoperative lung function than segments
      counting or scintigraphy (correlation and intraclass correlation coefficients,
      0.779-0.969 and 0.776-0.969; 0.573-0.887 and 0.552-0.882; and 0.578-0.834 and
      0.532-0.815, respectively), as well as greater accuracy, determined by narrower
      agreement coefficients for forced vital capacity, forced expiratory volume in 1
      second, lung diffusing capacity, and peak oxygen uptake. After validation in an
      independent cohort (n = 43), adjusted linear regression including volumetric
      estimation of decreased postoperative ventilation for postoperative lung function
      parameters explains 98% to 99% of variance. CONCLUSIONS: Volumetric computed
      tomography is a reliable and accurate method to predict postoperative lung
      function in patients undergoing lung resection that provides better accuracy than
      conventional procedures. Because lung computed tomography is systematically
      performed in the staging of patients with suspected lung cancer, this volumetric
      analysis might simultaneously provide the information necessary to evaluate
      operability.

PMID- 30195605
TI  - MRI-Linear Accelerator Radiotherapy Systems.
AB  - The desire to utilise soft-tissue image guidance at the time of radiation
      treatment has led to the development of several hybrid magnetic resonance imaging
      (MRI) linear accelerators (linacs). These systems have the potential to realise
      the benefits of MRI on the treatment table with the ability of real-time motion
      management and adaption on a patient-specific basis. There are several MRI-linacs
      currently being implemented covering both low and high magnetic field strength
      and two beam-field orientations. Clinical trials have only recently begun with
      this technology, but their future use as standard radiotherapy practice seems
      assured. This review article summarises the challenges faced in developing such
      hybrid technology, the differences and advantages of each of the currently
      exploited solutions, and their current status.

PMID- 30195606
TI  - Quantum chemical calculations and molecular modeling for methylene blue removal
      from water by a lignin-chitosan blend.
AB  - A comprehensive analysis of the molecular dynamics and quantum chemical
      calculation methods for methylene blue removal by adsorption were carried out.
      The experimentally measured adsorption data of methylene blue from water effluent
      on a novel lignin and chitosan blend were used to validate the modeling results.
      The method and required steps for application of quantum chemical calculations
      and molecular modeling techniques as the state of the art approach for predictive
      modeling and investigation of adsorption were provided, and the model findings
      were validated by comparing with the experimental data; close agreement between
      the results was observed. The conductor-like screening model (COSMO) approach was
      used for calculation of equilibrium concentration of solute at the adsorbent
      solute interface. The results revealed that the approach is highly recommended as
      it provides an alternative assessment for feasibility analysis before any
      experiments to be undertaken, resulting in time and cost saving.

PMID- 30195608
TI  - Tween 80-modified hyaluronic acid-ss-curcumin micelles for targeting glioma:
      Synthesis, characterization and their in vitro evaluation.
AB  - Redox-sensitive micelles based onhydrophilic hyaluronic acid-ss-hydrophobic
      curcumin conjugate were designed as a novel delivery system for gliomas
      targeting. Furthermore, the obtained micelles were further functionalized with
      Tween 80 (CUR-THSC) for better brain penetration. Dynamic light scattering
      experiment and in vitro release study showed that the synthetic disulfide-linked
      conjugate possessed redox-sensitivity under high glutathione conditions.
      Spherical micelles with a mean particle size of 74.2 nm, negative zeta potential
      (-30.25 mV), high entrapment efficiency (94.12%) and drug loading (8.9%) were
      obtained. XRD analysis of micelles revealed amorphous form of the encapsulated
      drug. CUR-THSC micelles showed good plasma stability and did not induce any
      hemolysis in erythrocytes. In addition, highest cytotoxicity in G422 cells was
      observed compared to the free curcumin group and non-sensitive micelles group.
      These results indicate that the Tween 80-modified hyaluronic acid-ss-curcumin
      micelles could emerge as a promising platform for the delivery of curcumin in the
      treatment of gliomas.

PMID- 30195607
TI  - Pectin modification assisted by nitrogen glow discharge plasma.
AB  - This study is concerned with modification of high methoxy pectin (HMP) assisted
      by nitrogen AC glow discharge plasma. Intrinsic viscosity of plasma treated
      pectin (PTP) was measured as primary index for structural changes in pectin
      molecules at different plasma conditions. The intrinsic viscosity of pectin
      increased within 7 min of exposure to plasma treatment and then remained
      constant. According to Fourier Transform Infrared Spectrometry (FT-IR) analysis,
      the intensity of carboxylate peaks increased in PTP samples due to de
      esterification of pectin. Moreover, by decreasing the degree of esterification
      (DE) in PTP samples, the results of FT-IR were confirmed. Based on high
      performance size-exclusion chromatography (HPSEC) analysis, the molecular weight
      of PTP reduced. PTP gel had higher storage and loss modulus and shorter linear
      viscoelastic region. Moreover, X-ray diffraction (XRD) studies indicated an
      increase of crystallinity in PTP due to the formation of hydrogen bonds. Results
      revealed that nitrogen AC glow discharge plasma had significant influence on
      physicochemical and functional properties of pectin. The result of this study
      showed AC glow discharge plasma has promising potential towards modification of
      pectin.

PMID- 30195609
TI  - Starch-graft-polyacrylonitrile nanofibers by electrospinning.
AB  - Graft copolymer starch-graft-polyacrylonitrile (St-g-PAN) was synthesized by homo
      grafting acrylonitrile (AN) from water soluble starch as Ce(IV) was used as an
      initiator. St-g-PAN nanofibers were prepared via electrospinning St-g-PAN
      solution in dimethyl sulfoxide (DMSO). The effects of the spinning parameters
      such as flow rate, spinning voltage, and collector distance on the St-g-PAN
      nanofiber diameter were investigated. Fourier transform infrared spectra (FT-IR),
      solid-state nuclear magnetic resonance (13C NMR) and scanning electron microscope
      (SEM) were used to characterize the structure and surface morphology of the
      nanofibers. The results showed that the nanofiber diameter depended strongly on
      the processing parameters. Moreover, the nanofiber had good water resistance,
      biocompatibility, and tensile intensity. As the cyano groups on St-g-PAN
      nanofibers were transformed to amidoxime groups, the obtained St-g-PAO nanofiber
      displayed an excellent adsorption ability, with the adsorption of Cr 533.4 mg.g-1
      at pH = 2.0 as K2Cr2O7 solution 500 mg.L-1 in water was used as the adsorption
      target. Therefore, these St-g-PAN nanofibers may find potential applications in a
      wide variety of fields such as tissue engineering, pharmaceutics, energy, and
      environmental science and engineering.

PMID- 30195610
TI  - UV-mediated solid-state cross-linking of electrospinning nanofibers of modified
      collagen.
AB  - The modified collagen with double bonds was electrospun into nanofibers membrane
      cured with photo-initiated polymerization under UV irradiation. The morphology
      and chemical structures were characterized by SEM and FTIR. Both the water
      resistance and mechanical properties were improved after UV-crosslinking. Then 5
      Fluorouracil (5-FU) was used as a model drug to prepare drug-loaded collagen
      nanofiber membrane cured with photo-initiated polymerization under UV
      irradiation. In vitro release results showed that drug release could be
      effectively controlled through UV-crosslinking. Furthermore, the release
      mechanism of drugs from electrospun mats was confirmed to be Fickian diffusion.

PMID- 30195611
TI  - In-vivo anti-diabetic and wound healing potential of
      chitosan/alginate/maltodextrin/pluronic-based mixed polymeric micelles: Curcumin
      therapeutic potential.
AB  - Development of curcumin-loaded mixed polymeric micelles based on chitosan,
      alginate, maltodextrin, pluronic F127, pluronic P123, and tween 80, by thin-film
      hydration method has been investigated in Bisphenol A induced diabetics rats.
      Curcumin (C21H20O6) extracted from rhizomes of the "Curcuma longa" has attracted
      considerable attention of pharmaceutical researchers due to its low cost,
      excellent pharmacological activities and lesser side effects. Despite its diverse
      pharmacological properties, the therapeutic application of curcumin as an oral
      therapy has been limited due to its poor aqueous solubility, fixed chemical
      stability, and low bioavailability. In an attempt to overcome these limitations,
      we developed curcumin-loaded mixed polymeric micelles. Diabetes mellitus is a
      most common chronic carbohydrate metabolic disorder. The results clearly
      demonstrated the ability of developed formulation to reduce the elevated blood
      glucose level and lipid profile (total cholesterol, triglycerides). It maintained
      the body-weight, HDL cholesterol level, various biochemical parameters and
      accelerated the wound healing process when treated with these curcumin-based
      formulations. The treatment of curcumin loaded mixed polymeric formulations
      allowed a favorable inhibitory effect to these histopathological changes of
      liver, kidney, and pancreas. The newly developed curcumin-based formulations have
      proved superior therapeutic potential and excellent healing efficacy as compared
      to standard drugs and pure curcumin.

PMID- 30195612
TI  - Inhibitory kinetics and mechanism of flavonoids from lotus (Nelumbo nucifera
      Gaertn.) leaf against pancreatic alpha-amylase.
AB  - In this study, lotus leaf flavonoids (LLF) were found to show a notable
      inhibition activity on alpha-amylase in a mixed-type manner with IC50 value of
      (5.58 +/- 0.10) mg/mL. The intrinsic fluorescence of alpha-amylase was quenched
      by the interaction with LLF through a static quenching mechanism, and LLF-alpha
      amylase complex was spontaneously formed mainly driven by the hydrophobic
      interaction and hydrogen bonding. Multispectroscopic analyses (synchronous
      fluorescence, three-dimensional fluorescence, circular dichroism (CD) and fourier
      transform infrared spectra (FT-IR)) comprehensively demonstrated that the binding
      of LLF to alpha-amylase would change the conformation and microenvironment of
      alpha-amylase, resulting in inhibiting the enzyme activity. The present study
      indicated that LLF had potential to be as an ingredient in functional food for
      the prevention of type-2 diabetes.

PMID- 30195613
TI  - Green synthesis of silver nanoparticles, its characterization, and chaperone-like
      activity in the aggregation inhibition of alpha-chymotrypsinogen A.
AB  - Consumption of silver nanoparticles (AgNPs) has been increased many folds due to
      its antimicrobial actions resulting in its widespread incorporation into a wide
      range of biomedical and consumer products. Still, enough research is needed to
      clearly understand the effect of these nanoparticles on the conformations of
      important macromolecules like proteins under different pathophysiological
      conditions. Pointing towards the situation, we carefully designed an in vitro
      study to elucidate the effect of green AgNPs on the aggregation pattern of alpha
      chymotrypsinogen A at a human pathological body temperature. We observed that the
      B-AgNPs inhibited the aggregation in alphaCgn-A in a concentration-dependent
      manner showing maximum inhibition at 30 MUg/ml above which the effect of
      aggregation inhibition was reduced as evident at 40 and 50 MUg/ml concentrations
      of B-AgNPs. Further, in our in vitro analysis, we found that the B-AgNPs of lower
      sizes has potential chaperone-like activity at pathological body temperature,
      which can be used as a component of the drug to prevent protein aggregation after
      further verification in animal models.

PMID- 30195614
TI  - Extraction, characterization, utilization as wound dressing and drug delivery of
      Bletilla striata polysaccharide: A review.
AB  - This review provides updated information on a kind of active polysaccharides
      extracting from Chinese traditional herb Bletilla striata. Preliminary
      investigations have listed several isolation approaches of extracting Bletilla
      striata polysaccharide (BSP) and the characterization result showed that the
      backbone of BSP has mainly consisted of 1,4-linked mannosyl residues and 1,4
      linked glucosyl residues. Remarkably, this review sums up the exploitation of BSP
      as biomaterials, including the preparation, bioactivity and effect mechanism of
      BSP-based wound dressings and drug deliveries. BSP exhibits excellent healing
      function mainly due to its modulation of macrophages throughout inflammation and
      proliferation periods. BSP-based drug vehicles include micelles, nanoparticles,
      microspheres and microneedles which display anti-cancer functions of targeted
      delivering drugs and drug capability of itself as well. This review aims to pave
      the way for further exploitation of this compound in biomedical area.

PMID- 30195615
TI  - Identification of Vulnerable Carotid Plaques: Contrasting Results from Contrast
      Enhanced Ultrasound Scan Studies.

PMID- 30195616
TI  - Provider verification of electronic health record receipt and nonreceipt of
      direct-acting antivirals for the treatment of hepatitis C virus infection.
AB  - PURPOSE: Pharmacoepidemiologic studies using electronic health record data could
      serve an important role in assessing safety and effectiveness of direct-acting
      antiviral therapy for chronic hepatitis C virus (HCV) infection, but the validity
      of these data needs to be determined. We evaluated the accuracy of pharmacy fill
      records in the national Veterans Health Administration (VA) Corporate Data
      Warehouse (CDW) as compared to facility-level electronic health record. METHODS:
      Patients prescribed a direct-acting antiviral regimen at five VA sites between
      2014 and 2016 were randomly selected and reviewed. A random sample of patients
      with chronic HCV infection without evidence of HCV treatment during the study
      period also underwent chart review. We calculated positive predictive value and
      negative predictive value overall and by site. RESULTS: Of the 501 patients who
      received a total of 2416 prescriptions, 494 were validated using data extracted
      from CDW 6 months after the study period, yielding a positive predictive value of
      98.6% (95% confidence interval, 97.6%-99.6%). Of the 100 patients with chronic
      HCV infection without prescriptions for HCV treatment, 99 were confirmed not to
      have received antiviral treatment (negative predictive value, 99.0%; 95%
      confidence interval, 97.1%-100%). CONCLUSIONS: These findings provide assurance
      to researchers who use national VA CDW data for retrospective cohort studies that
      the CDW contains accurate information on HCV therapies in the modern treatment
      era.

PMID- 30195617
TI  - Nicotinamide riboside induces a thermogenic response in lean mice.
AB  - AIMS: Nicotinamide Riboside (NR) is a NAD+ booster with wide physiological
      repercussion including the improvement on glucose and lipid homeostasis,
      increasing the life expectancy in mammals. However, the effects of NR on
      metabolism are only partially known. Here, we evaluated the effects of NR on the
      thermogenic response, highlighting the brown adipose tissue (BAT) in lean mice.
      MAIN METHODS: Male C57BL/67 mice were supplement with NR (400 mg/Kg/day) during 5
      weeks. The Comprehensive Lab Animal Monitoring System (CLAMS) and thermographic
      images were used to evaluated the physiological effects of NR treatment. The BAT
      were extracted and analyzed by Western Blotting and qPCR. Also, bioinformatics
      analyses were performed to establish the connection between the NAD+ synthesis
      pathway in BAT and thermogenic response in several isogenic strains of BXD mice.
      KEY FINDINGS: Transcriptomic analysis revealed that genes involved in NAD+
      synthesis (Nampt and Nmnat1) in the BAT were negatively correlated with body
      weight and fat mass. The heat map showed a strong positive correlation between
      Nampt and Ucp1 mRNA in BAT and body temperature in several strains of BXD lean
      mice. The experimental approaches demonstrated that oral NR supplementation
      reduced the abdominal visceral fat depots, with discrete impact on oxygen
      consumption in C57BL/6J mice. Interestingly, NR significantly increased the body
      temperature, and this phenomenon was accompanied by high levels of UCP1 protein
      content and Pgc1alpha mRNA in BAT. SIGNIFICANCE: This study demonstrated the oral
      NR supplementation was sufficient to induce the thermogenic response in lean mice
      changing the BAT metabolism.

PMID- 30195618
TI  - Serum angiogenesis profile in gestational trophoblastic neoplasm using multiplex
      immunoassay.
AB  - AIMS: Gestational trophoblastic neoplasms (GTN) exemplify a rare, mostly curable
      but highly aggressive disease. It is often associated with a rapid formation of
      distant metastases and most likely with an intense neoangiogenesis processes. The
      aim of the study was to analyze markers in serum of patients with GTN before
      chemotherapy compared to healthy pregnant women. MAIN METHODS: In this study
      sixteen protein angiogenesis markers were evaluated in serum of 21 patients with
      GTN before chemotherapy and compared with healthy pregnant women. Markers were
      measured using BioPlex Pro Human Cancer Biomarker Panel 1 immunoassay. t-Tests
      and receiver operating characteristic curves were used for statistical analysis.
      KEY FINDINGS: Receiver operator curve analysis identified six proteins (sTIE-2,
      osteopontin, sIL-6alpha, sVEGFR-2, sEGFR, PECAM-1) which had sufficient
      sensitivity and specificity (AUC > 0,70) to distinguish GTN patients before the
      treatment from pregnant controls. The levels of three proteins (sTIE-2,
      osteopontin and sIL-6alpha) were altered in GTN patients before the treatment as
      compared to healthy controls (p = 0,0112; p = 0,0442; p = 0,0488, respectively)
      and thereby may serve as potential disease markers. SIGNIFICANCE: Serum
      concentration of proteins related to angiogenesis changes in the course of GTN
      and may appear useful in the diagnostic process of this disease.

PMID- 30195620
TI  - Bipolar transfer of the pectoralis major muscle for restoration of elbow flexion
      in 29 cases.
AB  - BACKGROUND: This study evaluated the functional outcomes of bipolar pedicled
      pectoralis major (PM) transfer to restore elbow flexion. METHODS: We
      retrospectively reviewed 29 transfers in 28 patients with a mean age of 31.2
      years (range, 5-65 years). The loss of elbow flexion was due to brachial plexus
      palsy in 24 patients, elbow flexors necrosis in 4, and poliomyelitis in 1. The
      entire PM muscle was mobilized and fixed proximally to the coracoid process.
      Intraoperative positioning and postoperative immobilization of the shoulder and
      the elbow flexed at 60 degrees  and 120 degrees , respectively, allowed direct
      distal fixation of the muscle to the biceps brachii tendon. RESULTS: At the last
      follow-up (mean, 13 months; range, 4-37 months), 41% of the transfers (n = 12)
      recovered grade 4 elbow flexion strength and were able to lift 2.2 kg on average
      (range, 0.5-5 kg), 52% (n = 15) recovered grade 3 strength, and 7% (n = 2) had a
      poor result (ie, grade 2 elbow flexion). The mean active elbow flexion was 100
      degrees  (ranging, 30 degrees -150 degrees ), and the patients had 0 degrees  to
      10 degrees  elbow flexion contracture. CONCLUSIONS: Our results indicate that
      bipolar PM transfer is a reliable and effective procedure to restore elbow
      flexion. Flexion of the shoulder and elbow allowed the transfer to reach the
      elbow fold and avoided an interposition graft between the distal PM and the
      biceps brachii tendon.

PMID- 30195619
TI  - Memory deficits and hippocampal inflammation in cerebral hypoperfusion and
      reperfusion in male rats: Neuroprotective role of vanillic acid.
AB  - Ischemic stroke is one of the leading causes of neurological deterioration and
      mortality worldwide. Neuroprotective strategies are being investigated to
      minimize cognitive deficits after ischemic events. Here we investigated the
      neuroprotective potential of vanillic acid (VA) in an animal model of transient
      bilateral common carotid artery occlusion and reperfusion (BCCAO/R). Adult male
      Wistar rats (250-300 g) were randomly divided in 4 groups and submitted to either
      cerebral hypoperfusion-reperfusion or a sham surgery after two-weeks of
      pretreatment with VA and/or normal saline. To induce the animal model of
      hypoperfusion, bilateral common carotid arteries were occluded (2VO model) for 30
      min, followed by 72 h of reperfusion. Subsequently, their cognitive performance
      was evaluated in a Morris water maze (MWM) test, and also hippocampi were removed
      for ELISA assays and TUNEL staining test. The results showed that 2VO
      significantly reduced the spatial memory performance in MWM. As well as, BCCAO/R
      increased the level of IL-6, TNF-alpha and TUNEL positive cells, and also
      decreased the contents of IL-10 in the hippocampus of vehicle- pretreated groups
      as compared to the sham-operated groups. Furthermore, 14 consecutive days
      pretreatment with VA significantly restored the spatial memory, decreased the
      levels of IL-6, TNF-alpha and TUNEL positive cells and also increased the IL-10
      levels in the hippocampi of the BCCAO/R rats. VA alone did not show any change
      neither in the status of various cytokines nor behavioral and TUNEL staining
      tests over sham values. Our data confirm that VA could potentially serve as a
      novel, promising, and accessible neuroprotective agent against cerebrovascular
      insufficiency states and vascular dementia.

PMID- 30195621
TI  - Arthroscopic versus open release of internal rotation contracture in the
      obstetrical brachial plexus paralysis (OBPP) sequela.
AB  - BACKGROUND: Latissimus dorsi (LD) and teres major (TM) tendon transfers are
      effective surgical procedures to improve shoulder abduction and external rotation
      for children with obstetrical brachial plexus palsy (OBPP). Open pectoralis major
      (PM) tendon Z-plasty and arthroscopic subscapularis (SS) release are 2 options
      for the release of internal rotation contractures to enhance muscle transfers.
      This study compared the functional results of LD and TM tendon transfers with
      open PM tendon Z-plasty or arthroscopic SS release. METHODS: The study included
      24 patients who underwent LD and TM tendon transfers for OBPP (9 arthroscopic SS
      release, 15 open PM tendon Z-plasty) with a mean follow-up of 41.33 months
      (range, 36-60 months) and 47.2 months (range, 36-60 months), respectively.
      Functional evaluation was made according to range of motion and Mallet scoring
      system. RESULTS: Shoulder abduction-external rotation degrees and scores in all
      sections of the Mallet scoring system significantly increased in both groups (P <
      .001). Postoperatively, the arthroscopic SS release group had significantly
      better abduction degrees (P = .003), total Mallet scores (P < .001), and superior
      abduction (P = .043), active external rotation (P = .043), hand-to-head (P =
      .043), and hand-to-mouth (P < .001) scores for the Mallet scoring system.
      DISCUSSION: Transfer of LD together with TM tendons combined with one of the
      internal rotation contracture release procedures yielded good clinical and
      functional results in patients younger than age 7, regardless of the type of
      release method. However, arthroscopic SS release, although requiring an
      experienced surgeon, revealed better clinical and functional outcomes and is
      considered to be a less invasive and superior method.

PMID- 30195622
TI  - Patient factors influencing outpatient satisfaction in patients presenting with
      shoulder pain.
AB  - BACKGROUND: Patient-based evaluation of health care has been gaining attention in
      the past 2 decades. The purpose of this study was to evaluate patient
      satisfaction in a shoulder outpatient clinic and determine which factors impact
      satisfaction levels. METHODS: Fifty-nine outpatients with shoulder complaints
      from December 2017 to January 2018 were included. Patient satisfaction was
      measured using the Clinician and Group Consumer Assessment of Healthcare
      Providers and Systems survey, and 2 methods of calculation were implemented: top
      box and average scores. The impacts of age, gender, diagnosis, duration with the
      provider, Patient-Reported Outcomes Measurement Information System score, Pain
      Catastrophizing Scale score, pain visual analog scale (VAS) score, and function
      VAS score on patient satisfaction were analyzed. Patients were divided into more
      satisfied and less satisfied groups, and logistic regression analysis was
      performed to determine which factors affect patient satisfaction. RESULTS: The
      median total average and top-box scores were 95.2% and 90%, respectively.
      Similarly, in the analysis of all variables, average scores were always higher
      than top-box scores. The function VAS score and Patient-Reported Outcomes
      Measurement Information System score significantly influenced satisfaction. When
      patients were divided into more satisfied and less satisfied groups, the odds of
      having a less satisfied score among patients with a function VAS score of less
      than 5 was 5.5 times that of patients with a score of 5 or greater (odds ratio of
      5.06 [95% confidence interval, 1.55-16.46] with P = .01 for univariate and
      adjusted odds ratio of 5.53 [95% confidence interval, 1.14-26.76] with P = .03
      for multivariate). CONCLUSION: Despite being calculated from the same question
      set, using the average-score method for the Clinician and Group Consumer
      Assessment of Healthcare Providers and Systems survey generally yields higher
      scores than the top-box method. Among patients with shoulder pathology, function
      of the shoulder, as measured on a VAS, was the most significant factor
      influencing patient satisfaction in the outpatient setting.

PMID- 30195623
TI  - The clinical diagnosis of equine sarcoids - Part 1: Assessment of sensitivity and
      specificity using a multicentre case-based online examination.
AB  - Equine clinicians and researchers often make the diagnosis of equine sarcoids
      (ES) on clinical assessment alone, without histopathological confirmation.
      However, the accuracy of the clinical diagnosis of ES has not been critically
      assessed. To assess sensitivity, specificity, positive and negative predictive
      values of the clinical diagnosis of ES, 40 clinical cases with histologically
      confirmed equine skin lesions (26 ES and 14 non-ES) were compiled in a
      representative online examination. For each case and lesion, at least one
      photograph and all relevant information were presented in a standardised format.
      This included the horse's signalment, lesion localisation, lesion progression,
      presence of other skin lesions, earlier treatments and response to treatment. No
      information relevant for the assessment of the lesion was intentionally withheld.
      Fourteen ES experts, 39 board-certified equine specialists, 103 equine
      practitioners and 25 novices categorised the cases into ES or non-ES and graded
      their level of diagnostic confidence on a scale from 1 to 6 for each case. The
      overall success rate was 82.0% while sensitivity and specificity were 83.3% and
      79.6%, respectively. The positive and negative predictive values were 88.4% and
      72.0%, respectively, in the tested population with a 66% prevalence of ES.
      However, less experienced veterinarians were frequently wrong in their clinical
      judgement despite a high level of diagnostic confidence. Therefore, the authors
      propose to develop a diagnostic tool to help clinicians optimise their selection
      of lesions requiring a biopsy. Ultimately, this will help reduce costs and
      morbidity generated by unnecessary diagnostic and therapeutic efforts.

PMID- 30195625
TI  - Adult onset hereditary hemochromatosis is associated with a novel recurrent
      Hemojuvelin (HJV) gene mutation in north Indians.
AB  - Hereditary hemochromatosis (HH) is a rare disorder in Indians and is not
      associated with the common mutation Cys282Tyr in HFE gene found in Caucasians.
      Non-HFE HH can be associated with mutations in HJV, HAMP, TFR2 and SLC40A1 genes.
      Nineteen unrelated north Indian HH patients were detected after screening 258
      chronic liver disease patients on the basis of increased transferrin saturation,
      ferritin levels >1000 ng/L and siderosis by Perl's stain on liver biopsy wherever
      available. Automated DNA sequencing was performed for the promoters and entire
      coding exons for HFE, HJV, HAMP, TFR2 and SLC40A1. A novel homozygous mutation at
      position p.Gly336Ter (c.1006 G>T) in exon 4 in HJV was identified in four adult
      unrelated patients. We encountered compound heterozygosity for p.Thr217Ile
      (c.650C>T) and p.His63Asp (c.187C>G) mutation of HFE gene in one patient. Two
      patients were compound heterozygous for two novel polymorphisms at c.-358 (G>A)
      and c.-36 (G>A) in 5'UTR of HJV gene. Our study shows a novel HJV gene mutation
      p.Gly336Ter as a recurrent mutation associated with HH in north Indians. Low
      index of suspicion, underlying nutritional iron deficiency and protective effect
      of menstrual blood loss may account for the late clinical presentation of
      juvenile HH.

PMID- 30195624
TI  - "For lack of knowledge, our people will perish": Using focus group methodology to
      explore African-American communities' perceptions of breast cancer and the
      environment.
AB  - Among women living in the United States, breast cancer is the second leading
      cause of cancer death. Disproportionate racial disparities in breast cancer
      exist, with African American (AA) women consistently having the highest rates of
      breast cancer related mortality despite lower incidence. This study attends to
      the Institute of Medicine's (IOM) call to action recommending the identification
      of effective strategies for communicating accurate and reliable breast cancer
      risk information to diverse audiences. Using focus group methodology, this study
      explores how AAs perceive and decipher information related to breast cancer and
      its relationship to their environment. Six focus groups were conducted. The
      sample (n = 50) was African American, 98% female, with an average age of 50.1
      years. The focus group protocol consisted of open-ended questions designed to
      elicit information about participants' perceptions of their environment and its
      link to breast cancer. Focus groups were audio recorded and professionally
      transcribed. Analysis of the focus group transcripts revealed themes pertaining
      to these categories: (1) general knowledge and beliefs about breast cancer, (2)
      perceived environmental risks factors for breast cancer, (3) importance of
      seeking knowledge about breast cancer and the environment, and (4) recommended
      communication strategies. The emergent themes reflect the knowledge participants
      possessed about breast cancer and environmental risk factors, in addition to
      concerns about the importance of possessing accurate information, and how
      culturally appropriate health communication strategies can be used to disseminate
      breast cancer knowledge in the community. Findings from this study can be used
      for culturally appropriate communication about breast cancer and the environment
      with AA communities.

PMID- 30195627
TI  - The clinical features and prognosis of the monoclonal gammopathy undetermined
      significance: A single center study.
AB  - The aim of this study was to identify the clinical features and prognosis of
      monoclonal gammopathy of undetermined significance (MGUS) in China. This single
      center study enrolled 111 subjects visited in Peking University People's hospital
      including 62 males and 49 females. Among them, IgG subtype, IgA subtype and IgM
      subtype were 56.31%, 28.16%, 5.83% respectively. 10.7% patients had the
      abnormality of convectional cytogenetic testing, while the interphase
      fluorescence in situ hybridization (FISH) made the positive rate increased to
      18.9%, and IgH rearrangement was most common. The positive rate of MAGE-C1/CT7
      was 73.8% in MGUS, but the expression level was 0.33%, lower than that in MM.
      After a median follow-up of 15.9 months, 5 cases were determined disease
      progression (PD), and 1 patient had died of disease progression, two died of the
      complication. MGUS is becoming increasingly important in China. Male had higher
      prevalence of MGUS, the most common subtype was IgG, and the IgA subtype was much
      higher which may be related to the air pollution. MGUS patients had a high
      positive rate of MAGE-C1/CT7 gene, but the expression level was low. Some
      patients with MGUS could progress to MM, systemic amyloidosis and other malignant
      diseases.

PMID- 30195626
TI  - Ultrastructural changes in peripheral blood leukocytes in alpha-synuclein
      knockout mice.
AB  - Effects of alpha-synuclein deficiency on cellular blood components have not been
      extensively investigated. This study evaluated ultrastructural changes of
      leukocytes in alpha-synuclein knockout (KO) mice using electron microscopy (EM).
      The following ultrastructural characteristics were quantified in leukocytes:
      mitochondria, primary granules, specific granules (SG), Golgi apparatus (GA),
      inclusions, rough-endoplasmic reticulum (RER), smooth-endoplasmic reticulum
      (SER), and cellular projections (CP). EM showed increased numbers or amounts of
      SG, inclusions, and SER in KO group (5.3 +/- 4.5 in WT vs. 14.1 +/- 10.3 in KO, p
      = 0.02; 0.4 +/- 0.9 in WT vs. 3.2 +/- 2.8 in KO, p = 0.007; and 7.7 +/- 6.7 in WT
      vs. 17.7 +/- 12.2 in KO, p = 0.03, respectively). Although CP number was not
      significantly different between the two groups (13.4 +/- 5.3 in WT vs. 16.3 +/-
      7.5 in KO, p = 0.32), their size and shapes were altered in KO mice. Notably,
      findings occurred in the setting of significant lymphopenia. alpha-Synuclein
      deficiency leads to changes in size and shape of secretory particles and
      increases in SER, SG, and inclusions, indicating a potential role for alpha
      synuclein in vesicular trafficking in leukocytes. Further studies are needed to
      elucidate functions mediated by alpha-synuclein.

PMID- 30195628
TI  - [Anesthetic management of endovascular treatment for acute ischemic stroke:
      Influences on outcome and complications].
AB  - BACKGROUND AND OBJECTIVES: The emerging use of endovascular therapies for acute
      ischemic stroke, like intra-arterial thrombectomy, compels a better understanding
      of the anesthetic management required and its impact in global outcomes. This
      article reviews the available data on the anesthetic management of endovascular
      treatment, comparing general anesthesia with conscious sedation, the most used
      modalities, in terms of anesthetic induction and procedure duration, patient
      mobility, occlusion location, hemodynamic parameters, outcome and safety; it also
      focuses on the state-of-the-art on physiologic and pharmacologic neuroprotection.
      CONTENTS: Most of the evidence on this topic is retrospective and contradictory,
      with only three small randomized studies to date. Conscious sedation was
      frequently associated with better outcomes, but the prospective evidence declared
      that it has no advantage over general anesthesia concerning that issue. Conscious
      sedation is at least as safe as general anesthesia for the endovascular treatment
      of acute ischemic stroke, with equivalent mortality and fewer complications like
      pneumonia, hypotension or extubation difficulties. It has, however, a higher
      frequency of patient agitation and movement, which is the main cause for
      conversion to general anesthesia. CONCLUSIONS: General anesthesia and conscious
      sedation are both safe alternatives for anesthetic management of patients
      submitted to endovascular thrombectomy. No anesthetic management is universally
      recommended and hopefully the ongoing randomized clinical trials will shed some
      light on the best approach; meanwhile, the choice of anesthesia should be based
      on the patient's individual characteristics. Regarding neuroprotection,
      hemodynamic stability is currently the most important strategy, as no
      pharmacological method has been proven effective in humans.

PMID- 30195629
TI  - [Ultrasound dynamics of gastric content volumes after the ingestion of coconut
      water or a meat sandwich. A randomized controlled crossover study in healthy
      volunteers].
AB  - BACKGROUND: Adequate preoperative fasting is critical in preventing pulmonary
      aspiration of gastric content. We proposed to study the sonographic gastric
      content dynamics after the ingestion of liquid or solid food in healthy
      volunteers and confront it with current guidelines for preoperative fasting
      times. METHODS: We performed a prospective, crossover, evaluator-blinded study
      involving 17 healthy volunteers of both sexes. Each participant fasted for 10h
      and was subjected to a baseline gastric ultrasound, intake of 400mL of coconut
      water or a 145g, 355kcal meat sandwich, and sonographic gastric evaluations after
      10min and every hour until the stomach was completely empty. RESULTS: At
      baseline, all subjects had an empty stomach. At 10min, gastric content [mean +
      standard deviation (SD)] was 240.4 + 69.3 and 248.2 + 119.2mL for liquid and
      solid foods, respectively (p>0.05). Mean + SD gastric emptying times were 2.5 +
      0.7 and 4.5 + 0.9h for liquid and solid foods, respectively (p<0.001). For the
      drink, the stomach was completely empty in 59% and 100% of the subjects after two
      and four hours, and for the sandwich, 65% and 100% of the subjects after four and
      seven hours, respectively. CONCLUSIONS: Sonographic gastric dynamics for coconut
      water and a meat sandwich resulted in complete gastric emptying times higher and
      lower, respectively, than those suggested by current guidelines for preoperative
      fasting.

PMID- 30195630
TI  - [Effects of propofol pretreatment on myocardial cell apoptosis and SERCA2
      expression in rats with hepatic ischemia/reperfusion].
AB  - INTRODUCTION: Hepatic ischemia-reperfusion injury is a common pathophysiological
      process in liver surgery. Whether Propofol can reduce myocardial ischemia
      reperfusion injury induced by hepatic ischemia-reperfusion injury in rats,
      together with related mechanisms, still needs further studies. OBJECTIVE: To
      investigate if propofol would protect the myocardial cells from apoptosis with
      hepatic ischemia-reperfusion injury. METHODS: Male Sprague-Dawley rats (n=18)
      were randomly allocated into three groups: Sham Group (Group S, n=6), Hepatic
      Ischemia-reperfusion Injury Group (Group IR, n=6) and Propofol Group (Group P,
      n=6). Group S was only subjected to laparotomy. Group IR was attained by ischemia
      for 30min and reperfusion for 4h. Group P was subjected identical insult as in
      Group IR with the administration of propofol started 10min before ischemia with
      120mg.kg-1, following by continuous infusion at 20mg.kg-1.h-1. Cell apoptosis was
      examined by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end
      labeling assay. Endoplasmic reticulum Ca2+-ATPase2 (SERCA2) and cysteine
      containing aspartic acid cleaved-caspase3 (cleaved-caspase3) were assayed by
      western blot and Altimeter polymerase chain reaction. RESULTS: Apoptosis rate was
      increased, with mRNA and protein of SERCA2 down-regulated and cleaved-caspase3 up
      regulated in Group IR compared with Group S (p<0.01). Apoptosis rate was
      decreased, with mRNA and protein of SERCA2 up-regulated and cleaved-caspase3 down
      regulated in Group P compared with Group IR (p<0.01). CONCLUSIONS: Propofol can
      reduce hepatic ischemia-reperfusion injury-induced myocardial cell apoptosis,
      meanwhile, can up-regulate mRNA and protein of SERCA2 in rats.

PMID- 30195631
TI  - [Continuous quadratus lumborum type 3 block provides effective postoperative
      analgesia for hip surgery].
AB  - INTRODUCTION: Hip surgery is a major surgery that causes severe postoperative
      pain. Although pain during rest is usually considerably reduced mobilization is
      important in terms of thromboembolic complications. The quadratus lumborum block
      is a regional analgesic technique that blocks T6-L3 nerve branches. This block
      may provide adequate analgesia and reduce opioid consumption after hip surgery.
      CASE REPORT: We performed continuous quadratus lumborum type 3 block in two
      patients who underwent hip arthroplasty. Postoperative 24-h pain scores, local
      anesthetic consumptions on patient-controlled analgesia and additional analgesic
      requirement were recorded. In two patients, postoperative pain scores were less
      than 6 during rest and physiotherapy. Patient was mobilized in the early
      postoperative period without additional opioid analgesic requirement and without
      muscle weakness. DISCUSSION: Continuous quadratus lumborum block may be used to
      relieve postoperative acute pain in hip surgery because it provides one-sided
      anesthesia without muscle weakness.

PMID- 30195632
TI  - Characterize the difference between TMPRSS2-ERG and non-TMPRSS2-ERG fusion
      patients by clinical and biological characteristics in prostate cancer.
AB  - The TMPRSS2-ERG gene fusion were frequently found in prostate cancer, and thought
      to play some fundamental mechanisms for the development of prostate cancer.
      However, until now, the clinical and prognostic significance of TMPRSS2-ERG gene
      fusion was not fully understood. In this study, based on the 281 prostate cancers
      that constructed from a historical watchful waiting cohort, the statistically
      significant associations between TMPRSS2-ERG gene fusion and clinicopathologic
      characteristics were identified. In addition, the Elastic Net algorithm was used
      to predict the patients with TMPRSS2-ERG fusion status, and good predictive
      results were obtained, indicating that this algorithm was suitable to this
      prediction problem. The differential gene network was constructed from the
      network, and the KEGG enrichment analysis demonstrated that the module genes were
      significantly enriched in several important pathways.

PMID- 30195634
TI  - Impact of Human Activities on Fasciolosis Transmission.
AB  - Fasciolosis is a worldwide disease caused by the liver fluke Fasciola spp. This
      food- and water-borne disease is a major public health and veterinary issue. It
      is currently (re)emerging in several regions mainly due to the rapid evolution of
      human activities. This article reviews the current knowledge of the impact of
      irrigation-system management, livestock management, and human diet and hygiene
      habits on the emergence of fasciolosis. We also identify the gaps in this
      knowledge and the possible solutions for limiting these impacts. Integrated
      control seems to be the most effective solution for controlling fasciolosis,
      because it enables monitoring, prevention, and rapid action in case of the
      (re)emergence of the disease.

PMID- 30195633
TI  - Association between vascular endothelial growth factor rs699947 polymorphism and
      the risk of three major urologic neoplasms (bladder cancer, prostate cancer, and
      renal cell carcinoma): A meta-analysis involving 11,204 subjects.
AB  - BACKGROUND: The relationship between vascular endothelial growth factor (VEGF)
      gene variant rs699947 polymorphism and urologic neoplasms risk was studied
      extensively in recent years. The VEGF gene plays a key role in angiogenesis of
      urologic neoplasms, but some conclusions are still inconclusive. The aim of this
      study was to determine whether this polymorphism is a risk factor for
      susceptibility to urologic neoplasms by conducting a meta-analysis. METHODS: We
      performed a meta-analysis of 15 different publications from the PubMed, Embase
      and Medline databases, to better assess the association between VEGF rs699947
      polymorphism and urologic neoplasms risk. Odds ratios (ORs) and 95% confidence
      intervals (CIs) were evaluated using random or fixed effects models. RESULTS: By
      pooling all eligible studies, we found that the VEGF rs699947 polymorphism was
      not associated with overall urologic neoplasms. However, subgroup analysis based
      on cancer types demonstrated that significantly increased association was found
      between VEGF rs699947 polymorphism and the risk of bladder cancer (BCa) under
      heterozygous genetic model (OR = 1.48, 95%CI = 1.17-1.89). And rs699947
      polymorphism was also identified an increased risk of renal cell carcinoma (RCC)
      under dominant, recessive, homozygous, heterozygous and allelic contrast genetic
      models, while no association was observed in prostate cancer (PCa). In addition,
      in subgroup analysis by ethnicity, we found rs699947 polymorphism was associated
      with Asian population under dominant, homozygous, heterozygous and allelic
      contrast genetic models. No evidence of publication bias was found (Begg's test,
      P = 0.855; Egger's test, P = 0.590). CONCLUSIONS: In summary, our study showed
      evidence that the VEGF rs699947 polymorphism was obviously associated with an
      increased risk of bladder cancer and renal cell carcinoma, particularly in Asian
      population, while no significant association was observed in overall urologic
      neoplasms. Future studies with larger sample sizes are warranted to further
      evaluate these associations in more details.

PMID- 30195635
TI  - Proteomics of Anopheles Vectors of Malaria.
AB  - Proteomic investigations in Anopheles gained momentum following the sequencing of
      the Anopheles gambiae genome, allowing peptide data from mass spectrometry to be
      searched against large datasets of predicted protein sequences. Exhaustive
      discovery proteomics investigations have improved the annotation of genomic
      datasets and catalogued proteins from mosquito tissues, including the salivary
      glands, midgut, and sensory appendages. These efforts have revealed protein
      constituents that define the unique biological functions of these organs.
      Quantitative proteomics investigations have begun to characterise the molecular
      basis of mosquito behaviour and immune responses. With a current trend towards
      increasing sensitivity of mass spectrometers and simpler workflows, proteomics is
      set to accelerate the development of antiparasite interventions through the
      identification of new targets for parasite or vector control and diagnostic
      biomarkers.

PMID- 30195637
TI  - Analysis of competing endogenous RNA network to identify the key RNAs associated
      with prostate adenocarcinoma.
AB  - OBJECTIVES: Prostate adenocarcinoma (PRAD) is the most common cancer in men. The
      aim of this study was to reveal the critical long non-coding RNA (lncRNAs),
      microRNA (miRNAs) and mRNAs involved in the pathogenesis of PRAD. METHODS: The
      level 3 mRNA and miRNA sequencing data of PRAD were downloaded from The Cancer
      Genome Atlas database. Using the edgeR package of R, the differentially expressed
      mRNAs (DEGs), lncRNAs (DE-lncRNAs) and miRNAs (DE-miRNAs) between PRAD and normal
      tissues were screened. The Cox proportional hazards regression method in the
      survival package was used to select the lncRNAs significantly related to clinical
      characteristics. After the miRNA-lncRNA and miRNA-mRNA pairs were predicted, a
      regulatory network was constructed by the Cytoscape software. For the DEGs
      involved in the network, enrichment analysis was conducted by the Fisher
      algorithm. RESULTS: Compared to the normal samples, 25 DE-lncRNAs, 1421 DEGs and
      68 DE-miRNAs were identified in the PRAD samples. The down-regulated MESTIT1 had
      a significantly negative correlation with overall survival. A total of 44 DE
      miRNA-DE-lncRNA pairs were predicted, including the PCA3-miR-96 and UCA1-miR-96.
      Meanwhile, 33 DEGs targeted by miRNAs (for example, miR-96-CYP19A1) were found to
      correlate with cancers. CONCLUSION: Functional enrichment analysis showed that
      the reproductive development process (which involved TDRD1) was enriched for the
      DEGs implicated in the lncRNA-miRNA-mRNA regulatory network. The lncRNAs MESTIT1,
      PCA3, and UCA1; mRNAs CYP19A1 and TDRD1; as well as miR-96 might affect the
      pathogenesis of PRAD.

PMID- 30195636
TI  - miR-93-3p alleviates lipopolysaccharide-induced inflammation and apoptosis in
      H9c2 cardiomyocytes by inhibiting toll-like receptor 4.
AB  - BACKGROUND: miR-93 is recently recognized to perform anti-inflammatory action in
      the pathological process of cardiomyocytes dysfunction. However, it remains
      unclear whether miR-93-3p involves in lipopolysaccharide (LPS)-induced
      inflammation and apoptosis in H9c2 cells. The present study aimed to investigate
      the functions of miR-93-3p and its target, toll-like receptor 4 (TLR4), in LPS
      stimulated cardiomyocytes. MATERIAL AND METHODS: Cell viability was analyzed by
      CCK-8 assay. AnnexinV-FITC/PI staining and lactate dehydrogenase (LDH) assay were
      used to evaluate the cell death. The mRNA and protein levels were assayed by RT
      qPCR and western blotting, respectively. The targeted gene was predicted by a
      bioinformatics algorithm and confirmed by a dual luciferase reporter assay.
      RESULTS: LDH stimulation resulted in the suppression of cell viability and the
      increase in apoptosis rate, inflammatory cytokines and LDH levels, while
      inhibition of TLR4 with TAK-242 or overexpression of miR-93-3p dramatically
      blocked LPS-induced inflammation and apoptosis in cardiomyocytes. Intriguingly,
      bioinformatics analysis and experimental data suggested that TLR4 was a direct
      target of miR-93-3p, which could inhibit TLR4 expression by transfected with miR
      93-3p mimics or elevate the expression of TLR4 by transfected with miR-93-3p
      inhibitors. Overexpression of TLR4 carried out an opposite effect to miR-93-3p
      and positively regulated LPS-induced inflammation and apoptosis in
      cardiomyocytes. CONCLUSION: miR-93-3p showed the protective effects against LPS
      induced inflammation and apoptosis in cardiomyocytes by inhibiting TLR4
      expression.

PMID- 30195638
TI  - Comparison of prostatic adenocarcinoma Gleason 5 and intraductal carcinoma of the
      prostate with tumor necrosis. A morphometric study.
AB  - Intraductal carcinoma of the prostate(IDCP) is defined as a solid or cribriform
      neoplastic growth confined to ducts and acini, with preservation of the basal
      cell layer. Since IDCP can often present tumor necrosis (TN), it should be
      distinguished from Gleason 5 (GP5) invasive adenocarcinoma for staging and
      clinical purposes. In the present study we reviewed 344 radical prostatectomies
      performed at our institution and selected all cases with either >5% GP5 or IDCP
      for assessment of TN on histology slides (n = 59). A total of 19 cases with TN
      were identified, and morphology, size, location, and histoarchitecture of the
      lesions with TN were recorded. Subsequently, the corresponding sections were
      stained with a basal cell immunomarker (P63), and lesions with TN were assigned
      to IDCP or invasive carcinoma GP5 for comparison. Our results show that a
      branched shape and size 501-1000 MUm are more common in IDCP, while a size >1000
      MUm and location within 1 mm of the periprostatic soft tissue are significantly
      more prevalent in invasive adenocarcinoma GP5. These features, however, usually
      cannot be assessed in core biopsies. In this setting, the utilization of
      immunohistochemistry is warranted to differentiate IDCP and GP5 with necrosis.

PMID- 30195639
TI  - SGLT-2 Inhibitors and Peripheral Artery Disease: A Statistical Hoax or Reality?
AB  - Inhibitors of sodium-glucose cotransporters type-2 are the most recent addition
      to the armamentarium of oral antidiabetic agents. This class of drugs has shown
      promising results in glycemic control and most importantly to reduce
      cardiovascular disease (CVD) mortality risk. Despite the encouraging data, there
      is concern regarding their potential for causing or worsening peripheral artery
      disease (PAD), which may increase the risk of lower extremity amputations.
      Following the publication of results of CANVAS and CANVAS-R trials, which
      revealed that leg and mid-foot amputations occurred about twice as often in
      patients treated with canagliflozin compared to placebo, the Food and Drug
      Administration (FDA) in the United States issued a black box warning of leg and
      foot amputations associated with canagliflozin use. In this article, our main aim
      is to review the available evidence in preclinical and clinical studies regarding
      SGLT-2 inhibitors and PAD events, the possible mechanisms related to increased
      risk of amputation, to evaluate whether it is a class effect or individual drug
      effect, and most importantly, implications for their continued use as
      antidiabetic agents. It also raises the issue of including PAD events among the
      end-points when assessing future antihyperglycemic agents. Thus, we also tried to
      analyze whether outcomes of SGLT2 inhibitors trials mostly focused on stroke,
      myocardial infarction, heart failure, and peripheral vascular disease-related
      outcomes remained underrated.

PMID- 30195640
TI  - DNA double-strand breaks as drivers of neural genomic change, function, and
      disease.
AB  - Early work from about two decades ago implicated DNA double-strand break (DSB)
      formation and repair in neuronal development. Findings emerging from recent
      studies of DSBs in proliferating neural progenitors and in mature, non-dividing
      neurons suggest important roles of DSBs in brain physiology, aging, cancer,
      psychiatric and neurodegenerative disorders. We provide an overview of some
      findings and speculate on what may lie ahead.

PMID- 30195641
TI  - Biochemical attributes of mitotic and meiotic presynaptic complexes.
AB  - Homologous recombination (HR) is a universally conserved mechanism used to
      maintain genomic integrity. In eukaryotes, HR is used to repair the spontaneous
      double strand breaks (DSBs) that arise during mitotic growth, and the programmed
      DSBs that form during meiosis. The mechanisms that govern mitotic and meiotic HR
      share many similarities, however, there are also several key differences, which
      reflect the unique attributes of each process. For instance, even though many of
      the proteins involved in mitotic and meiotic HR are the same, DNA target
      specificity is not: mitotic DSBs are repaired primarily using the sister
      chromatid as a template, whereas meiotic DBSs are repaired primarily through
      targeting of the homologous chromosome. These changes in template specificity are
      induced by expression of meiosis-specific HR proteins, down-regulation of mitotic
      HR proteins, and the formation of meiosis-specific chromosomal structures. Here,
      we compare and contrast the biochemical properties of key recombination
      intermediates formed during the pre-synapsis phase of mitotic and meiotic HR.
      Throughout, we try to highlight unanswered questions that will shape our
      understanding of how homologous recombination contributes to human cancer biology
      and sexual reproduction.

PMID- 30195642
TI  - What happens at the lesion does not stay at the lesion: Transcription-coupled
      nucleotide excision repair and the effects of DNA damage on transcription in cis
      and trans.
AB  - Unperturbed transcription of eukaryotic genes by RNA polymerase II (Pol II) is
      crucial for proper cell function and tissue homeostasis. However, the DNA
      template of Pol II is continuously challenged by damaging agents that can result
      in transcription impediment. Stalling of Pol II on transcription-blocking lesions
      triggers a highly orchestrated cellular response to cope with these cytotoxic
      lesions. One of the first lines of defense is the transcription-coupled
      nucleotide excision repair (TC-NER) pathway that specifically removes
      transcription-blocking lesions thereby safeguarding unperturbed gene expression.
      In this perspective, we outline recent data on how lesion-stalled Pol II
      initiates TC-NER and we discuss new mechanistic insights in the TC-NER reaction,
      which have resulted in a better understanding of the causative-linked Cockayne
      syndrome and UV-sensitive syndrome. In addition to these direct effects on lesion
      stalled Pol II (effects in cis), accumulating evidence shows that transcription,
      and particularly Pol II, is also affected in a genome-wide manner (effects in
      trans). We will summarize the diverse consequences of DNA damage on
      transcription, including transcription inhibition, induction of specific
      transcriptional programs and regulation of alternative splicing. Finally, we will
      discuss the function of these diverse cellular responses to transcription
      blocking lesions and their consequences on the process of transcription restart.
      This resumption of transcription, which takes place either directly at the lesion
      or is reinitiated from the transcription start site, is crucial to maintain
      proper gene expression following removal of the DNA damage.

PMID- 30195643
TI  - Antiquorum sensing and biofilm potential of 5- Hydroxymethylfurfural against Gram
      positive pathogens.
AB  - The present investigates the antiquorum sensing and biofilm inhibitory potential
      of 5 - hydroxymethylfurfural against Chromobacterium violaceum, Streptococcus
      pyogenes, Streptococcus mutans, Staphylococcus aureus and Staphylococcus
      epidermidis. 5HMF inhibits the quorum sensing mediated violacein pigment
      production by 87% at 100 MUg/ml concentration. A 100 MUg/ml concentration of the
      compound inhibits S. mutans and S. epidermidis biofilm formation by 86% and 79%
      whereas for S. pyogenes and S. aureus 125 MUg/ml concentration inhibits biofilm
      formation by 83% and 82%. The Confocal images clearly indicate that 5HMF as a
      promising antibiofilm agent.

PMID- 30195644
TI  - Venom as therapeutic weapon to combat dreadful diseases of 21st century: A
      systematic review on cancer, TB, and HIV/AIDS.
AB  - Cancer and infectious diseases are the preeminent causes of human morbidities and
      mortalities worldwide. At present, chemotherapy, radiotherapy, immunotherapy, and
      gene therapy are considered as predominant options in order to treat cancer. But
      these therapies provide inadequate consequences by affecting both the normal and
      tumor cells. On the other hand, tuberculosis (TB), and HIV (human
      immunodeficiency virus) infections are significant threats, causing over a
      million mortalities each year. The extensive applications of antibiotics have
      caused the microbes to acquire resistance to the existing antibiotics. With the
      emerging dilemma of drug resistant microbes, it has become imperative to identify
      novel therapeutic agents from natural sources as emphatic alternative approach.
      Over the past few decades, venoms derived from several reptiles, amphibians, and
      arthropods including snakes, scorpions, frogs, spiders, honey bees, wasps,
      beetles, caterpillars, ants, centipedes, and sponges have been identified as
      efficient therapeutics. Venoms constitute plethora of bioactive components,
      particularly peptides, enzymes, and other chemical entities, which exhibit a
      large array of anticancer and anti-pathogenic activities. This review highlights
      the panorama of bioactive components of animal venoms divulging the anticancer,
      anti-tubercular, and anti-HIV activities. In a nutshell, this context discloses
      the decisive role of animal venoms as alternative natural resources to combat
      these deadly diseases of 21st century, and propounding the plausible development
      of new therapeutic drugs in the present era.

PMID- 30195645
TI  - Prevalence of the Helicobacter pylori homA and homB genes and their correlation
      with histological parameters in children.
AB  - The significance of Helicobacter pylori (H. pylori) virulence genes such as cagA
      and vacA has been extensively studied in children; however, data regarding the
      significance of homA and homB genes are scarce. The aim of our study was to
      evaluate the prevalence and clinical relevance of these genes in Slovenian
      children. All children diagnosed with H. pylori infection between 1993 and 2013
      were included in the study (n = 343). DNA was extracted from biopsy specimens
      previously used for the rapid urease test. Five histological parameters were
      evaluated and the presence of the vacA, cagA, iceA, babA2, and homA and homB
      genes was determined by PCR amplification. The homA and homB genes were detected
      in 174/285 (61.1%) and 116/285 (40.7%) strains, respectively. The presence of the
      homA gene was significantly associated with the absence of the homB gene (P <
      0.001); however, no associations were found between the presence of either the
      homA or homB genes and any of the other investigated virulence genes. Similarly,
      there were no correlations between the presence of the homA and homB genes and
      any of the histological parameters. In contrast, genotype profiles vacA
      s1m1/cagA+/babA2+/homB+, vacA s1m2/cagA+/babA2+/homA+, vacA
      s1m1/cagA+/babA2+/homA+, vacA s1m1/cagA+/babA2-/homA+, vacA s1m2/cagA-/babA2
      /homA+, and vacA s2m2/cagA-/babA2-/homB+ were associated with a higher degree of
      gastric mucosal damage. Thus, although the homA and homB genes did not represent
      important individual virulence markers in this population, they may act
      synergistically with other H. pylori virulence genes, causing severe gastritis in
      children.

PMID- 30195646
TI  - Immunological characteristics of Mycobacterium tuberculosis subunit vaccines
      immunized through different routes.
AB  - Tuberculosis is chronic infectious disease caused by Mycobacterium tuberculosis
      (M.tb) that is prevalent worldwide. Several specific antigens, such as Antigen
      85B (Ag85B) and 6 kDa early secretory antigenic target (ESAT-6) protein of M.tb,
      are listed as some of the candidate subunit vaccines against M.tb. ESAT-6, as a
      virulent factor and differential gene in M.tb, shows insufficient immunogenicity
      in animal model. In order to investigate the ways to improve the immunogenicity
      of ESAT-6, we immunized ESAT-6 by subcutaneous and intramuscular routes with
      different adjuvants. We found that ESAT-6 immunized alone did not induce
      significant humoral immunity in both immunization routes. However, subcutaneous
      immunization of ESAT-6 plus incomplete Freund's adjuvant can induce a significant
      humoral immune response, enhanced proliferation and elevated secretion of IFN
      gamma from splenocytes. Intramuscular immunization of ESAT-6 plus adjuvant
      aluminum salt or poly(I:C) did not enhance humoral and cellular immune responses.
      Therefore, it is concluded that immunization of ESAT-6 subcutaneously plus
      incomplete Freund's adjuvant induces stronger humoral and cellular immune
      responses, which can be considered of ESAT-6 as a subunit vaccine in further
      research against tuberculosis.

PMID- 30195647
TI  - Phenotypic and functional features of innate and adaptive immunity as putative
      biomarkers for clinical status and leprosy reactions.
AB  - The aim of this study was to identify phenotypic and functional biomarkers
      associated with distinct clinical status of leprosy or leprosy reactions. The
      study included tuberculoid/borderline (BB/BT/T) and lepromatous (BL/L) leprosy
      poles as well as Type-1 and Type-2 leprosy reactions along with healthy controls
      (NI). A range of peripheral blood biomarkers of innate (neutrophils - NEU and
      monocytes - MON) and adaptive immunity (CD4+ and CD8+ T-cells) were evaluated ex
      vivo and upon in vitro stimuli with M. leprae antigen. Data analysis allowed the
      selection of NEUTLR4+ (ex vivo) and CD4+IL-10+ (in vitro) as universal biomarkers
      increased in all leprosy patients and those exhibiting leprosy reactions. A range
      of biomarkers were commonly found in both poles of leprosy patients, including
      decreased levels of MONTGF-beta+ (ex vivo) and increased levels of MONTNF-alpha+,
      CD4+TGF-beta+, CD8+TLR2+, CD8+TNF-alpha+, CD8+IL-4+ and CD8+TGF-beta+ (in vitro).
      Noteworthy was that MONHLA-DR+ (ex vivo) and CD8+IL-10+ (in vitro) were
      particularly found in BL/L patients. Leprosy patients with Type-1 reaction
      exhibited a larger list of altered biomarkers, mainly involving activation
      markers (TLR2, TLR4, HLA-DR and DAF-2T) in NEU and MON along with CD4+ and CD8+
      cells. In summary, this study provided insights about immunological features of
      leprosy poles and leprosy reactional episodes with putative applicability,
      including novel biomarkers for complementary diagnosis and future therapeutic
      approaches in clinical studies.

PMID- 30195648
TI  - A novel insight into fluid bed melt granulation: Temperature mapping for the
      determination of granule formation with the in-situ and spray-on techniques.
AB  - The in-line control of pharmaceutical processes has become a necessary tool for
      the evaluation and follow-up of pharmaceutical dosage forms. In this study, a
      novel approach to the evaluation of conditions established in a conical fluid bed
      granulator during the in-situ and spray-on fluid bed melt granulation (FBMG)
      techniques was developed. The determination of temperature mappings allowed the
      characterization of the critical zones during the melt granulation and the
      prediction of the volume of the wetting zone, hence enabling the identification
      of the areas of optimal granule growth. Two grades of polyethylene glycol (PEG
      2000 and 6000) were used as meltable binders in three binder spraying rates and
      droplet size fractions for spray-on and three binder particle sizes and contents
      for in-situ. The results showed the presence of intense heat exchange in the
      bottom of the bed during the in-situ technique and under the spraying nozzle
      during the spray-on technique, identified as the wetting zone. Isotherm maps
      enabled the identification of the transition between the wetting, cooling and
      consolidation zones for the spray-on and the cooling zone for the in-situ
      technique. The shape and volume of the wetting zone was highly dependent on
      binder spraying rate and spraying pressure for spray-on and binder particle size
      and content for in-situ FBMG. Granule size and size distribution were correlated
      to the volume of the wetting zone and an optimized wetting volume interval was
      determined for both spray-on and in-situ techniques for the optimal quality
      attributes of the granules.

PMID- 30195649
TI  - Intracochlear drug delivery: Fluorescent tracer evaluation for quantification of
      distribution in the cochlear partition.
AB  - Measurement of drug distribution in the inner ear has important roles in the
      design of local delivery methods, such as direct, intracochlear delivery, and in
      assessment of emerging drug candidates in preclinical animal models. Sampling
      methods have been used in the past to measure drug concentrations in the cochlear
      fluids, but these methods provide no direct information about drug distribution
      in the cochlear tissues. In this work, we evaluated four fluorescent markers that
      simulate drug distribution in the organ of Corti after intracochlear delivery to
      the cochlea's scala tympani compartment. Our hypothesis is that ultimately, a
      cocktail comprising several fluorescent drug surrogates or fluorescently-tagged
      drugs, each with differing distribution, spreading, and clearance behavior, can
      be used to evaluate both transient and cumulative drug distributions associated
      with different delivery techniques. In this study, FITC-dextran, QtrackerTM 655,
      gentamicin Texas-Red, and FM 1-43 FX were each evaluated as candidate markers by
      direct intracochlear infusion into guinea-pig cochleae. Distribution of the
      markers was measured using fluorescence confocal microscopy imaging of cochlear
      whole mount dissections from animals sacrificed 3 h after the tracer-infusion.
      For all four tracers, strong fluorescence was observed in the tissue sections
      near the base, but only QtrackerTM-655, gentamicin Texas-Red (GTTR) and FM 1-43
      FX exhibited any specificity in labelling of the sensory hair cells. Therefore,
      these substances represent leading candidates for the quantification drug
      distribution achieved by different delivery approaches to the scala tympani.

PMID- 30195650
TI  - Mechanistic study on hydrodynamics in the mini-scale biphasic dissolution model
      and its influence on in vitro dissolution and partitioning.
AB  - Biphasic dissolution models were proposed to provide good predictive power for in
      vivo absorption kinetics. However, up to date the impact of hydrodynamics in mini
      scale models are not well understood. Consequently, the aim of this work was to
      investigate different setups of a previously published mini-scale biphasic
      dissolution model (miBIdi-pH-II) to better understand the relevance of
      hydrodynamics for evaluating kinetic parameters and to simultaneously increase
      the robustness of the experimental model. As a first step, the hydrodynamics
      within the aqueous phase were characterized by in silico simulations of the flow
      patterns. Different settings, such as higher rotation speeds of the paddles, the
      implementation of a second propeller into the aqueous phase, and different shapes
      of aqueous stirrers were investigated. Second, to evaluate the results of the in
      silico simulations, in vitro experiments with glitter were carried out. Last, the
      same settings were applied in the miBIdi-pH-II using dipyridamole (DPD) as model
      compound to estimate kinetic parameters by applying a compartment-based modelling
      approach. Both in vitro experiments with glitter or DPD demonstrated the
      adequateness of the previous in silico hydrodynamic simulations. The use of
      higher rotation speeds and a second aqueous propeller resulted in more
      homogeneous mixing of the aqueous phase. This resulted in faster distribution of
      dissolved active pharmaceutical ingredient (API) into the octanol phase. A
      kinetic model was successfully applied to quantify the influence of hydrodynamics
      on the partitioning rate of the API into the octanol phase. In conclusion, the
      combination of in silico and in vitro methods was demonstrated to be powerful for
      investigating the flow patterns within the miBIdi-pH-II. A comprehensive
      understanding of the hydrodynamics and the respective influence on the
      dissolution and apparent partitioning into the octanol phase in the biphasic
      dissolution model was obtained and completed by using a compartmental kinetic
      model. This model allowed successful quantification of how the hydrodynamics
      influence the partitioning of API into the octanol phase.

PMID- 30195651
TI  - The needs of families of trauma intensive care patients: A mixed methods study.
AB  - OBJECTIVE: To identify the needs of families of trauma patients in the Intensive
      Care Unit and to assess nurses' perceptions of those needs. METHODOLOGY: A
      sequential mixed-methods study was utilised combining survey data and semi
      structured interviews. SETTING: A tertiary Intensive Care Unit in Australia.
      OUTCOME MEASURES: The Critical Care Family Needs Inventory assessed the needs of
      families of general and trauma patients. Nurses were also surveyed for their
      perspectives on the needs of trauma patients' families. Interviews with families
      were analysed using an inductive thematic analysis technique. RESULTS/FINDINGS:
      214 surveys were completed (50 family members of trauma patients; 53 family
      members of general patients; 111 nurses). No statistically significant sub-scale
      differences in survey responses between the family groups were found. However,
      differences on four of the five survey sub-scales (p <= .001) were identified
      between families of trauma patients and nurses. Three themes emerged identifying
      unique needs of families of trauma patients from the interviews and included:
      Personal Distress and Adjustment,Guidance, and Care. CONCLUSION: This mixed
      methods study identified that families of trauma patients have different needs to
      families of general patients and the nurses rated the needs of the families of
      trauma patients as less important than the families rated their own needs.
      Through a collaborative partnership with these families, nurses can assist and
      better meet their needs. The provision of individualised patient/family-centred
      care is likely to have a positive influence.

PMID- 30195652
TI  - Inter-scan Reproducibility of Carotid Plaque Volume Measurements by 3-D
      Ultrasound: Methodological Issues to Avoid Misinterpretation.

PMID- 30195654
TI  - Modern Dual-Mobility Cups in Revision Total Hip Arthroplasty: A Systematic Review
      and Meta-Analysis.
AB  - BACKGROUND: The purpose of this systematic review is to analyze the outcomes of
      dual-mobility (DM) cups in revision total hip arthroplasty (THA). Specifically,
      we evaluated the following: (1) all-cause and aseptic survivorship rates; (2)
      dislocation rates; (3) complications; and (4) clinical outcomes reported using
      validated health status measures. METHODS: A comprehensive literature search
      included studies that reported the following: (1) re-revision rates, (2)
      complications, and (3) clinical outcomes following DM use in revision THA. The
      following exclusion criteria were used: (1) studies that did not stratify their
      analysis between primary and revision THA, (2) studies that utilized off-label
      techniques, (3) review articles, (4) case studies, (5) basic science articles,
      (6) non-English language reports, and (6) reports on patients who underwent
      surgery before 2010, in order to reflect modern DM implants use and technology. A
      total of 9 studies were included in our final analysis. RESULTS: Aseptic and all
      cause survivorship rates were 97.7% and 94.5%. Prevalence of dislocation was
      2.2%, and 0.3% for intraprosthetic dislocation. Meta-analysis comparing DM to
      fixed-bearing prostheses demonstrated a significantly lower odds of dislocation
      in the DM cohort (odds ratio 0.24, P = .002). Complications occurred in 7.4% of
      revision THAs with DM cups, while infection rates totaled to 3.3% of cases.
      Studies comparing outcomes using Harris Hip Scores did not demonstrate a
      statistically significant difference in improved postoperative scores (P > .05).
      CONCLUSION: DM cups have demonstrated excellent survivorship, low dislocation,
      and overall complication rates. Therefore, it can be considered a safe and
      effective option, particularly in the high-risk patients who undergo revision
      THA.

PMID- 30195653
TI  - LncRNA HOTAIR epigenetically suppresses miR-122 expression in hepatocellular
      carcinoma via DNA methylation.
AB  - BACKGROUND: MicroRNA-122 (miR-122), a pivotal liver-specific miRNA, is frequently
      repressed in hepatocellular carcinoma (HCC) and associated with poor prognosis.
      Long non-coding RNA (lncRNA) HOTAIR has been proved to function as an oncogene in
      multiple cancers including HCC. However, the relationship between HOTAIR and miR
      122 in HCC remains largely unknown. METHODS: We investigated the function of
      HOTAIR and miR-122 in HCC cell models and a xenograft mouse model. The regulatory
      network between HOTAIR and miR-122 was further detected following overexpression
      or knockdown of HOTAIR. DNA methylation status of miR-122 promoter region, as
      well as expression levels of DNMTs, EZH2 and Cyclin G1 were analyzed. FINDINGS:
      In this study, we found that HOTAIR was highly expressed whereas miR-122 was
      suppressed in HCC, and HOTAIR negatively regulated miR-122 expression in HCC
      cells. Furthermore, knockdown of HOTAIR dramatically inhibited HCC cell
      proliferation and induced cell cycle arrest in vitro and suppressed
      tumorigenicity in vivo by upregulating miR-122 expression. Mechanistically, a CpG
      island was located in the miR-122 promoter region. HOTAIR epigenetically
      suppressed miR-122 expression via DNMTs-mediated DNA methylation. Moreover,
      HOTAIR upregulated DNMTs expression via EZH2. In addition, suppression of miR-122
      induced by HOTAIR directly reactivated oncogene Cyclin G1 expression.
      Collectively, our results suggest that HOTAIR epigenetically suppresses miR-122
      expression via DNA methylation, leading to activation of Cyclin G1 and promotion
      of tumorigenicity in HCC, which provide new insight into the mechanism of HOTAIR
      mediated hepatocarcinogenesis via suppressing miR-122.

PMID- 30195655
TI  - Influence of Posterior Tibial Slope on Kinematics After Cruciate-Retaining Total
      Knee Arthroplasty.
AB  - BACKGROUND: The purpose of this study was to investigate the influence of
      posterior tibial slope (PTS) on knee kinematics after cruciate-retaining total
      knee arthroplasty (CR-TKA). These influences were evaluated using a prosthesis
      designed with high geometric conformity to the medial articular surface under the
      weight-bearing condition of deep knee bending. METHODS: We evaluated 71 knees (52
      patients) after CR-TKA using 2- to 3-dimensional registration techniques. All
      patients were categorized into 2 groups: group A (PTS <= 7 degrees ) and group B
      (PTS >= 8 degrees ). We compared in vivo knee kinematics during deep knee bending
      under weight-bearing conditions between the 2 groups. The anteroposterior
      position of the nearest points, flexion angles, and external rotation angles of
      the femoral components relative to the tibial components were evaluated.
      Additionally, the knee flexion angles of the femur relative to the tibia obtained
      from the installation angles of the components were evaluated. RESULTS: PTS did
      not affect the external rotation angles and anteroposterior position. The
      postoperative maximum flexion angle and range of motion between the femur and
      tibia in group B were significantly greater than those in group A. CONCLUSION:
      PTS of 8 degrees  or more in CR-TKA using prosthetics designed with high
      geometric conformity to the medial articular surface did not affect the
      anteroposterior position and external rotation, but increased the postoperative
      maximum flexion angle and range of motion.

PMID- 30195656
TI  - Assessment of mammographic breast density after sleeve gastrectomy.
AB  - BACKGROUND: Mammographic breast density (BD) is an independent risk factor for
      breast cancer. The effects of bariatric surgery on BD are unknown. OBJECTIVES: To
      investigate BD changes after sleeve gastrectomy (SG). SETTING: University
      hospital, United States. METHODS: Fifty women with mammograms before and after SG
      performed from 2009 to 2015 were identified after excluding patients with a
      history of breast cancer, hormone replacement, and/or breast surgery. Patient
      age, menopausal status, co-morbidities, hemoglobin A1C, and body mass index were
      collected. Craniocaudal mammographic views before and after SG were interpreted
      by a blinded radiologist and analyzed by software to obtain breast imaging
      reporting and data system density categories, breast area, BD, and absolute dense
      breast area (ADA). Analyses were performed using chi2, McNemar's test, t test,
      and linear regressions. RESULTS: Radiologist interpretation revealed a
      significant increase in breast imaging reporting and data system B+C category
      (68% versus 54%; P = .0095) and BD (9.8 +/- 7.4% versus 8.3 +/- 6.4%; P = .0006)
      after SG. Software analyses showed a postoperative decrease in breast area
      (75,398.9 +/- 22,941.2 versus 90,655.9 +/- 25,621.0 pixels; P < .0001) and ADA
      (7287.1 +/- 3951.3 versus 8204.6 +/- 4769.9 pixels; P = .0314) with no
      significant change in BD. Reduction in ADA was accentuated in postmenopausal
      patients. Declining breast area was directly correlated with body mass index
      reduction (R2 = .4495; P < 0.0001). Changes in breast rather than whole body
      adiposity better explained ADA reduction. Neither diabetes status nor changes in
      hemoglobin A1C correlated with changes in ADA. CONCLUSIONS: ADA decreases after
      SG, particularly in postmenopausal patients. Software-generated ADA may be more
      accurate than radiologist-estimated BD or breast imaging reporting and data
      system for capturing changes in dense breast tissue after SG.

PMID- 30195658
TI  - Excessive postextraction bleeding associated with Cordyceps sinensis: a case
      report and review of select traditional medicines used by Vietnamese people
      living in the United States.
AB  - Many older people who have emigrated from Vietnam to the United States continue
      to use the traditional medicines that they used in their country of origin.
      Clinicians trained in the West may not be familiar with these products. We
      reviewed 6 Asian traditional medicines that are popular among older Vietnamese
      people living in the United States. Each medicine has significant side effects
      that can lead to complications in patients undergoing surgery. Here, we present
      the case of a patient who used Cordyceps sinensis daily as a tonic and
      experienced prolonged bleeding after dental surgery.

PMID- 30195657
TI  - Psychosocial functioning and quality of life in patients with loose redundant
      skin 4 to 5 years after bariatric surgery.
AB  - BACKGROUND: Bariatric surgery usually results in substantial weight loss and a
      reduction in medical comorbidities. Many patients, as a consequence of the weight
      loss, subsequently evidence loose, redundant skin. OBJECTIVES: This investigation
      seeks to examine the prevalence of body contouring surgery (BCS) by patients
      approximately 4 to 5 years after Roux-en-Y gastric bypass surgery. Demographics,
      change in BMI, and psychosocial variables were also used to predict body
      dissatisfaction, desire for BCS, and patients who reported obtaining BCS.
      SETTING: The clinical sites involved in the Longitudinal Assessment of Bariatric
      Surgery project, which included 10 hospitals across the United States. METHODS:
      The sample comprised 1159 patients who underwent Roux-en-Y gastric bypass and
      were enrolled in the Longitudinal Assessment of Bariatric Surgery-2 study.
      Participants were surveyed using the Excessive Skin Survey and other psychosocial
      measures at their 4- or 5-year postoperative outcome. The participants were
      predominately women (80.5%), Caucasian (88.3%), and middle-aged (mean = 46.1 yr,
      standard deviation = 11.11 yr). RESULTS: Participants reported modest degrees of
      being bothered by excessive skin, primarily in their waist/abdomen, thighs, and
      chest/breasts body areas. Only 11.2% of the sample had undergone any BCS
      procedure, and a majority of those participants paid "out of pocket" for BCS.
      Desire for BCS and body dissatisfaction 4 to 5 years postsurgery was associated
      with higher depression scores and poorer quality of life scores. CONCLUSIONS:
      Excessive skin is associated with poorer psychosocial functioning. Despite
      reporting modest levels of being bothered by excessive skin and body
      dissatisfaction, only a small fraction of participants underwent BCS. Cost of BCS
      was reported to be a primary barrier for not obtaining BCS. All rights reserved.

PMID- 30195659
TI  - Identification of target gene and prognostic evaluation for lung adenocarcinoma
      using gene expression meta-analysis, network analysis and neural network
      algorithms.
AB  - BACKGROUND: Lung adenocarcinoma (LUAD) is a heterogeneous disease with poor
      survival in the advanced stage and a high incidence rate in the world. Novel drug
      targets are urgently required to improve patient treatment. Therefore, we aimed
      to identify therapeutic targets for LUAD based on protein-protein and protein
      drug interaction network analysis with neural network algorithms using mRNA
      expression profiles. RESULTS: A comprehensive meta-analysis of selective non
      small cell lung cancer (NSCLC) mRNA expression profile datasets from Gene
      Expression Omnibus were used to identify potential biomarkers and the molecular
      mechanisms related to the prognosis of NSCLC patients. Using the Network Analyst
      tool, based on combined effect size (ES) methods, we recognized 6566
      differentially expressed genes (DEGs), which included 3036 downregulated and 3530
      upregulated genes linked to NSCLC patient survival. ClueGO, a Cytoscape plugin,
      was exploited to complete the function and pathway enrichment analysis, which
      disclosed "regulated exocytosis", "purine nucleotide binding", "pathways in
      cancer", and "cell cycle" between exceptionally supplemented terms. Enrichr, a
      web tool examination, demonstrated "early growth response protein 1 (EGR-1)",
      "hepatocyte nuclear factor 4alpha (HNF4A)", "mitogen-activated protein kinase 14
      (MAP3K14)", and "cyclin-dependent kinase 1 (CDK1)" to be among the most prevalent
      TFs and kinases associated with NSCLC. Our meta-analysis identified that MAPK1
      and aurora kinase (AURKA) are the most obvious class of hub nodes. Furthermore,
      protein-drug interaction network and neural network algorithms identified
      candidate drugs such as phosphothreonine and 4-(4-methylpiperazin-1-yl)-n-[5-(2
      thienylacetyl)-1,5-dihydropyrrolo[3,4-c]pyrazol-3-yl] benzamide and for the
      targets MAPK1 and AURKA, respectively. CONCLUSION: Our study has identified novel
      candidate biomarkers, pathways, transcription factors (TFs), and kinases
      associated with NSCLC prognosis, as well as drug candidates, which may assist
      treatment strategy for NSCLC patients.

PMID- 30195661
TI  - Efficacy of brief behavioral treatment for insomnia in older adults: examination
      of sleep, mood, and cognitive outcomes.
AB  - OBJECTIVE: The aim of the present study was to examine the effects of a brief
      behavioral intervention for insomnia (BBTi) on sleep parameters, mood, and
      cognitive functioning in older adults. METHODS: Older adults (aged 65 years or
      more) underwent four weekly sessions of BBTi or self-monitoring control (SMC).
      Participants completed 14 days of sleep diaries and actigraphy measuring sleep
      onset latency (SOL), wake after sleep onset (WASO), total sleep time (TST), sleep
      efficiency (SE), and sleep quality ratings at baseline, post-treatment, and three
      month follow-up. Participants also completed mood scales (Geriatric Depression
      Scale [GDS]; Beck Depression Inventory-II; and State Trait Anxiety Inventory) and
      neuropsychological testing (measuring global cognition, language, memory,
      attention and processing speed, and executive function) at the three timepoints.
      RESULTS: Significant condition (BBTi vs. SMC) x time (baseline vs. post-treatment
      vs. follow-up) interactions revealed that BBTi improved relative to baseline in
      sleep diary-reported SOL, WASO, SE, and sleep quality, and these improvements
      were maintained at follow-up. SMC showed no change in these measures. A main
      effect of time showed that actigraphy-measured WASO improved from baseline for
      both BBTi and SMC at post-treatment. A main effect of time revealed that both
      BBTi and SMC patients endorsed fewer GDS symptoms relative to baseline at post
      treatment and follow-up. We observed no change in performance on
      neuropsychological measures. CONCLUSIONS: A four-week BBTi is an efficacious
      intervention for reducing insomnia symptoms in older adults. BBTi does not
      selectively improve mood or cognitive functioning. Future work should examine
      effects of BBTi on physiological measures of sleep architecture and day-to-day
      cognition. CLINICAL TRIAL IDENTIFER: NCT02967185.

PMID- 30195662
TI  - Quantitative Analysis of Surgical Residency Reform: Using Case-Logs to Evaluate
      Resident Experience.
AB  - BACKGROUND: Curricular changes at a mid-sized surgical training program were
      developed to rebalance clinical rotations, optimize education over service,
      decrease the size of service teams, and integrate apprenticeship-type
      experiences. This study quantifies the operative experience before and after
      implementation as part of a mixed-methods program evaluation. STUDY DESIGN:
      Retrospective review of case-log data and data from the Accreditation Council for
      Graduate Medical Education (ACGME) and the American College of Surgeons National
      Surgical Quality Improvement Program: quality in-training initiative to evaluate
      case volume pre- and postintervention. RESULTS: 11,365 cases, excluding "first
      assistant" and "endoscopic" cases, were logged for an average of 291 and 263
      cases/resident pre- and postintervention, respectively. Average case volume
      increased significantly for postgraduate year (PGY) 3 residents and decreased
      significantly for PGY 4 residents between the two time periods. Variability was
      observed among residents at the same PGY level both pre- and postintervention,
      with coefficients of variation of 6.0% to 34.1% in 2014 to 2015 and 11.2% to
      66.8% in 2015 to 2016. Inter-resident variability persisted when comparing a
      specific procedure between ACGME case-log and quality in-training initiative data
      sets. CONCLUSION: The data suggest that inter-resident variability in case load
      is not an artifact of case logging behavior alone, but may reflect personal
      preferences and choices in case selection that are not impacted by curriculum
      change. Logging behavior and accuracy of case-logs may contribute to variability.
      The shift in case load from PGY 4 to PGY 3 after curriculum implementation
      requires validation by ongoing analysis of ACGME case-log data.

PMID- 30195660
TI  - An evaluation of clinical order patterns machine-learned from clinician cohorts
      stratified by patient mortality outcomes.
AB  - OBJECTIVE: Evaluate the quality of clinical order practice patterns machine
      learned from clinician cohorts stratified by patient mortality outcomes.
      MATERIALS AND METHODS: Inpatient electronic health records from 2010 to 2013 were
      extracted from a tertiary academic hospital. Clinicians (n = 1822) were
      stratified into low-mortality (21.8%, n = 397) and high-mortality (6.0%, n = 110)
      extremes using a two-sided P-value score quantifying deviation of observed vs.
      expected 30-day patient mortality rates. Three patient cohorts were assembled:
      patients seen by low-mortality clinicians, high-mortality clinicians, and an
      unfiltered crowd of all clinicians (n = 1046, 1046, and 5230 post-propensity
      score matching, respectively). Predicted order lists were automatically generated
      from recommender system algorithms trained on each patient cohort and evaluated
      against (i) real-world practice patterns reflected in patient cases with better
      than-expected mortality outcomes and (ii) reference standards derived from
      clinical practice guidelines. RESULTS: Across six common admission diagnoses,
      order lists learned from the crowd demonstrated the greatest alignment with
      guideline references (AUROC range = 0.86-0.91), performing on par or better than
      those learned from low-mortality clinicians (0.79-0.84, P < 10-5) or manually
      authored hospital order sets (0.65-0.77, P < 10-3). The same trend was observed
      in evaluating model predictions against better-than-expected patient cases, with
      the crowd model (AUROC mean = 0.91) outperforming the low-mortality model (0.87,
      P < 10-16) and order set benchmarks (0.78, P < 10-35). DISCUSSION: Whether
      machine-learning models are trained on all clinicians or a subset of experts
      illustrates a bias-variance tradeoff in data usage. Defining robust metrics to
      assess quality based on internal (e.g. practice patterns from better-than
      expected patient cases) or external reference standards (e.g. clinical practice
      guidelines) is critical to assess decision support content. CONCLUSION: Learning
      relevant decision support content from all clinicians is as, if not more, robust
      than learning from a select subgroup of clinicians favored by patient outcomes.

PMID- 30195663
TI  - Communication Deficits Among Surgical Residents During Difficult Patient Family
      Conversations.
AB  - OBJECTIVES: To qualitatively analyze videotaped data of surgical residents and
      fellows interacting with standardized patients to identify communication
      weaknesses. To correlate our qualitative data with their quantitative scores.
      DESIGN: We used discourse analysis to identify negative communication patterns
      among 10 surgical residents and fellows who were tested on interpersonal
      competencies during an objective structured clinical examination in 2014. We then
      correlated our findings with the validated evaluation outcomes. Descriptive
      statistics were then used to quantify our findings. SETTING: The setting was an
      objective structured clinical examination performed in 2014 using standardized
      patient surrogate family members. PARTICIPANTS: The participants were a mix of
      first and third year surgical residents and critical care fellows. RESULTS: The
      item that most strongly differentiated the bottom 5 from the top 5 performers was
      not answering the patient appropriately. This was exhibited in 3 ways among the
      lowest performers in our study: (1) paternalism, (2) vagueness, and (3)
      dehumanization. Our statistical analyses showed that the overall number of
      negative communication behaviors correlated with negative staff scores (r = 
      0.653, p < 0.05). Dehumanization and paternalism were the 2 behaviors most
      strongly correlated with negative staff scores (r = 0.796 and 0.781 respectively,
      p < 0.01). CONCLUSIONS: We found the lowest performers responded inappropriately
      to the patient, which we further delineated into vagueness, paternalism, and
      dehumanization. We propose positive communication strategies be taught to
      residents to improve how they are perceived by patients.

PMID- 30195664
TI  - Do Not Blame the Resident: the Impact of Surgeon and Surgical Trainee Experience
      on the Occurrence of Intraoperative Adverse Events (iAEs) in Abdominal Surgery.
AB  - OBJECTIVE: Intraoperative adverse events (iAEs) are defined as inadvertent
      injuries that occur during an operation and are associated with increased
      mortality, morbidity, and health care costs. We sought to study the impact of
      attending surgeon experience as well as resident training level on the occurrence
      of iAEs. DESIGN: The institutional American College of Surgeons-National Surgical
      Quality Improvement Program and administrative databases for abdominal surgeries
      were linked and screened for iAEs using the International Classification of
      Diseases, Ninth Revision, Clinical Modification-based Patient Safety Indicator
      "accidental puncture/laceration." Each flagged record was systematically reviewed
      to confirm iAE occurrence and determine the number of years of independent
      practice of the attending surgeon and the postgraduate year (PGY) of the
      assisting resident at the time of the operation. The attending surgeon experience
      was divided into quartiles (<6 years, 6-13 years, 13-20 years, >20 years). The
      resident experience level was defined as Junior (PGY-1 to PGY-3) or Senior (PGY-4
      or PGY-5). Univariate/bivariate then multivariable logistic regression analyses
      adjusting for patient demographics, comorbidities, and operation type and/or
      complexity (using RVUs as a proxy) were performed to assess the independent
      impact of resident and attending surgeon experience on the occurrence of iAEs.
      SETTING: A large tertiary care teaching hospital. PARTICIPANTS: Patients included
      in the 2007-2012 ACS-NSQIP that had an abdominal surgery performed by both an
      attending surgeon and a resident. RESULTS: A total of 7685 operations were
      included and iAEs were detected in 159 of them (2.1%). Junior residents
      participated in 1680 cases (21.9%), while senior residents were involved in 6005
      (78.1%). The iAE rates for attending surgeons with <6, 6-13, 13-20, and >20 years
      of experience were 2.7%, 1.7%, 2.4%, and 1.4%, respectively. In multivariable
      analyses, the risk of occurrence of an iAE was significantly decreased for
      surgeons with >20 years of experience compared to those with <6 years of
      experience (odds ratio=0.52, 95% confidence interval 0.32-0.86, p = 0.011). On
      bivariate analyses, iAEs occurred in 1.2% of junior resident cases, while senior
      residents had an iAE rate of 2.3%. However, after risk adjustment on
      multivariable analyses, the resident experience level did not significantly
      impact the rate of iAEs. CONCLUSIONS: The surgeon's level of experience, but not
      the resident's, is associated with the occurrence of iAEs in abdominal surgery.
      Efforts to improve patient safety in surgery should explore the value of pairing
      junior surgeons with the more experienced ones thru formalized coaching programs,
      rather than focus on curbing resident operative autonomy.

PMID- 30195665
TI  - A Pilot Study of Inpatient Satisfaction Rating of Surgical Resident Care.
AB  - OBJECTIVE: To describe inpatient satisfaction with surgical resident care given
      the increasing importance of patient satisfaction as a quality metric. DESIGN:
      Surgical inpatients were invited to complete a survey that addressed their
      satisfaction with and attitudes regarding surgical resident care. The survey was
      based on the Consumer Assessment of Healthcare Providers and Systems Surgical
      Care Survey (S-CAHPS). Patients were required to positively identify photos of
      resident physicians prior to providing ratings. Adapted S-CAHPS items were scored
      using the "top-box" method. SETTING: Massachusetts General Hospital, a tertiary
      academic center. PARTICIPANTS: General surgery inpatients recovering from
      elective, major abdominal surgery were recruited on postoperative days 2 to 4.
      RESULTS: Ninety-one percent of approached patients participated (102/112, mean
      age = 62.9, 51.6% male). Patients positively identified both seniors and interns
      88% of the time. Thirteen seniors and 19 interns were rated, with 1 to 14
      evaluations per trainee. Overall quality of care ratings for seniors and interns
      were 9.35 and 9.09, respectively (0-10 scale, 10 = "best possible care"). Sixty
      three percent of senior resident evaluations and 60% of intern evaluations
      received a score of 10. The proportion of residents receiving top-box scores
      ranged from 59.5% to 97.7% depending on the item. Forty percent of senior
      resident and 38% of intern evaluations received top-box scores for all 8 items.
      Over 96% of patients reported strong or moderate agreement with the statements "I
      feel it is important to help in the education of future surgeons." CONCLUSIONS:
      Surgical inpatients willingly completed ratings about their surgery residents,
      typically can recognize their resident physicians, and rate quality of care
      highly. Despite many high ratings, there is room for improvement in some S-CAHPS
      domains. These results indicate patients are a valuable source of feedback
      regarding a resident's progress in several core competencies such as
      interpersonal skills, communication, professionalism, and patient care.

PMID- 30195666
TI  - A scoping review of Chikungunya virus infection: epidemiology, clinical
      characteristics, viral co-circulation complications, and control.
AB  - Chikungunya fever is a mosquito-borne viral illness characterized by a sudden
      onset of fever associated with joint pains. It was first described in the 1950s
      during a Chikungunya virus (CHIKV) outbreak in southern Tanzania and has since
      (re-) emerged and spread to several other geographical areas, reaching large
      populations and causing massive epidemics. In recent years, CHIKV has gained
      considerable attention due to its quick spread to the Caribbean and then in the
      Americas, with many cases reported between 2014 and 2017. CHIKV has further
      garnered attention due to the clinical diagnostic difficulties when Zika (ZIKV)
      and dengue (DENV) viruses are simultaneously present. In this review, topical
      CHIKV-related issues, such as epidemiology and transmission, are examined. The
      different manifestations of infection (acute, chronic and atypical) are described
      and a particular focus is placed upon the diagnostic handling in the case of ZIKV
      and DENV co-circulating. Natural and synthetic compounds under evaluation for
      treatment of chikungunya disease, including drugs already licensed for other
      purposes, are also discussed. Finally, previous and current vaccine strategies,
      as well as the control of the CHIKV transmission through an integrated vector
      management, are reviewed in some detail.

PMID- 30195667
TI  - Ethanol extract of Curcuma longa rhizome mitigates potassium bromate-induced
      liver changes in the Wistar rat: Histological, histochemical and
      immunohistochemical assessments.
AB  - The effects of Curcuma longa rhizome on hepatic cells, glycogen, connective
      tissue fibres and filamentous cytoskeleton were evaluated following KBrO3-induced
      liver injury in Wistar rats. Thirty-five male rats were randomly divided into
      seven groups (n=5). Group 1 were normal saline treated rats. Hepatic injury was
      induced in groups 2 to 7 by oral administration of 100mg/kg KBrO3 for 2 weeks.
      Following induction, rats in group 2 were sacrificed while groups 3, 4, 5 were
      given oral dose of EECLOR at 100, 200, 400mg/kg respectively. Group 6 rats were
      treated with silymarine while group 7 rats were left untreated. The rats were
      sacrificed and the liver sections were stained with H&E, Masson trichrome, Gordon
      and Sweets, PAS, Feulgen reaction, anti-vimentin antibody for demonstration of
      general histoarchitecture, elastic fibre, collagen fibre; glycogen, nuclear DNA
      and filamentous cytoskeleton respectively. Groups 2, 3, 7 developed intranuclear
      vacuolation, plasma coagulation, plamolysis, karyopyknosis, karyorrhexis and
      karyolysis, hyperchromatism, DNA fading and pleomorphism. Immunohistochemical
      study revealed near negative immunoreaction for vimentin. These pathological
      changes were ameliorated in EECLOR-treated groups in a manner comparable to
      silymarine-treated group. The study concluded that ameliorative effects of EECLOR
      in KBrO3-induced liver injury could be due to its vimentin stabilization
      property.

PMID- 30195668
TI  - Preface.

PMID- 30195669
TI  - Investigating missing sources of glyoxal over China using a regional air quality
      model (RAMS-CMAQ).
AB  - Currently, modeling studies tend to significantly underestimate observed space
      based glyoxal (CHOCHO) vertical column densities (VCDs), implying the existence
      of missing sources of glyoxal. Several recent studies suggest that the emissions
      of aromatic compounds and molar yields of glyoxal in the chemical mechanisms may
      both be underestimated, which can affect the simulated glyoxal concentrations. In
      this study, the influences of these two factors on glyoxal amounts over China
      were investigated using the RAMS-CMAQ modeling system for January and July 2014.
      Four sensitivity simulations were performed, and the results were compared to
      satellite observations. These results demonstrated significant impacts on glyoxal
      concentrations from these two factors. In case 1, where the emissions of aromatic
      compounds were increased three-fold, improvements to glyoxal VCDs were seen in
      high anthropogenic emissions regions. In case 2, where molar yields of glyoxal
      from isoprene were increased five-fold, the resulted concentrations in July were
      3-5-fold higher, achieving closer agreement between the modeled and measured
      glyoxal VCDs. The combined changes from both cases 1 and 2 were applied in case
      3, and the model succeeded in further reducing the underestimations of glyoxal
      VCDs. However, the results over most of the regions with pronounced anthropogenic
      emissions were still underestimated. So the molar yields of glyoxal from
      anthropogenic precursors were considered in case 4. With these additional mole
      yield changes (a two-fold increase), the improved concentrations agreed better
      with the measurements in regions of the lower reaches of the Yangtze River and
      Yellow River in January but not in July.

PMID- 30195671
TI  - Baosteel emission control significantly benefited air quality in Shanghai.
AB  - As the largest iron and steel producer in China, a part of Baosteel moved out of
      Shanghai deserves close attention due to its environmental impact. To understand
      the effect of Baosteel emission control on air quality in Shanghai, daily PM10,
      PM2.5, SO2, NO2 and CO were measured from 2010 to 2016. Concentrations of
      pollutants in Baoshan District presented a decreased trend during 2010-2016, with
      a reduction rate of 28.6% for PM10, 67.3% for SO2, 8.6% for NO2 and 42.0% for CO.
      However, fine particle pollution in Baoshan District during 2012-2016 seems to
      become more prominent, with PM2.5 concentration of 47+/-28, 45+/-33, 38+/-24,
      54+/-41 and 51+/-34MUg/m3, respectively, indicating a slight increase of 8.5% in
      PM2.5. Concentrations of PM10 and CO decreased by 12.5% and 33.8% in the second
      half year in 2016 (compared with that in 2015) probably due to closure of blast
      furnace of Baosteel. Baosteel was identified as the largest pollution source in
      Baoshan District. Emission from Baosteel accounted for 58.0% of SO2, 43.6% of NO2
      and 79.3% of dust in total emission from Baoshan District during 2010-2015.
      Meanwhile, pollutant emission and coal consumption from Baosteel decreased by
      52.0% for SO2, 40.1% for NO2, 15.7% for dust and 22% for coal consumption. Energy
      consumption in Baoshan District reduced by 31% from 2011 to 2015. Air quality
      improvement in Shanghai was attributed to local emission reduction, together with
      regional air quality improvement.

PMID- 30195670
TI  - Particulate matter pollution in Kunshan High-Tech zone: Source apportionment with
      trace elements, plume evolution and its monitoring.
AB  - Particulate matter (PM) in the Kunshan High-Tech zone is studied during a three
      month campaign. PM and trace elements are measured by the online pollution
      monitoring, forecast-warning and source term retrieval system AS3. Hourly
      measured concentrations of PM10, PM2.5 and 16 trace elements in the PM2.5 section
      (Ca, Pb, Cu, Cl, V, Cr, Fe, Ti, Mn, Ni, Zn, Ga, As, Se, Sr, Ba) are focused.
      Source apportionment of trace elements by Positive Matrix Factorization modeling
      indicates that there are five major sources, including dust, industrial
      processing, traffic, combustion, and sea salt with contribution rate of 23.68%,
      21.66%, 14.30%, 22.03%, and 6.89%, respectively. Prediction of plume dispersion
      from concrete plant and traffic emissions shows that PM10 pollution of concrete
      plant is three orders of magnitude more than that of the traffic. The influence
      range can extend to more than 3km in 1hr. Because the footprint of the industrial
      plumes is constantly moving according to the local meteorological conditions, the
      fixed monitoring sites scattered in a few hundred meters haven't captured the
      heaviest pollution plume at the local scale of a few km2. As a more intensive
      monitoring network is not operationally possible, the use of online modeling
      gives accurate and quantitative information of plume location, which increases
      the spatial pollution monitoring capacity and improves the understanding of
      measurement data. These results indicate that the development of the AS3 system,
      which combines monitoring equipment and air pollution modeling systems, is
      beneficial to the real-time pollution monitoring in the industrial zone.

PMID- 30195672
TI  - Atmospheric HULIS and its ability to mediate the reactive oxygen species (ROS): A
      review.
AB  - Atmospheric humic-like substances (HULIS) are not only an unresolved mixture of
      macro-organic compounds but also powerful chelating agents in atmospheric
      particulate matters (PMs); impacting on both the properties of aerosol particles
      and health effects by generating reactive oxygen species (ROS). Currently, the
      interests of HULIS are intensively shifting to the investigations of HULIS-metal
      synergic effects and kinetics modeling studies, as well as the development of
      HULIS quantification, findings of possible HULIS sources and generation of ROS
      from HULIS. In light of HULIS studies, we comprehensively review the current
      knowledge of isolation and physicochemical characterization of HULIS from
      atmospheric samples as well as HULIS properties (hygroscopic, surface activity,
      and colloidal) and possible sources of HULIS. This review mainly highlights the
      generation of reactive oxygen species (ROS) from PMs, HULIS and transition
      metals, especially iron. This review also summarized the mechanism of iron
      organic complexation and recent findings of OH formation from HULIS-metal
      complexes. This review will be helpful to carry out the modeling studies that
      concern with HULIS-transition metals and for further studies in the generation of
      ROS from HULIS-metal complexes.

PMID- 30195673
TI  - Characteristics of the pollutant emissions in a tunnel of Shanghai on a weekday.
AB  - Tunnel displays a typical semi-closed environment, and multitudes of the
      pollutants tend to accumulate. The samples of gaseous pollutants and particulate
      matter (PM) were collected from the Xiangyin tunnel at Shanghai to investigate
      the characteristics of the pollutant emissions. The results indicated that both
      gaseous pollutants and PM exhibited much higher concentrations during the rush
      hours in the morning and at night due to vehicle emission. Two peaks of the PM
      concentration were observed in the scope of 0.7-1.1 and 3.3-4.7 MUm, accounting
      for 14.6% and 20.3% of the total concentrations, respectively. Organic matter
      (OM), EC, and many water-soluble ions were markedly higher at the rush hours in
      the morning than those at night, implicating comprehensive effects of vehicle
      types and traffic volume. The particle number concentrations exhibited two peaks
      at Aitken mode (25 nm and 100 nm) and accumulation mode (600 nm), while the
      particle volume concentration displayed high values at the accumulation mode (100
      500 nm) and coarse mode (2.5-4.0 MUm). The peak around 100 nm was detected in the
      morning rush hours, but it diminished with the decrease of the traffic volume.
      Individual-particle analysis revealed that main particles in the tunnel were Fe
      rich particles, K-rich particles, mineral particles, Ca-S rich particles and Al
      Si particles. The particles collected at the rush hours displayed marked
      different morphologies, element concentrations and particle sizes compared to the
      ones collected at the non-rush period. The data presented herein could shed a
      light on the feature of vehicle emissions.

PMID- 30195674
TI  - Atmospheric isoprene and monoterpenes in a typical urban area of Beijing:
      Pollution characterization, chemical reactivity and source identification.
AB  - Continuous observation of isoprene, alpha-pinene and beta-pinene was carried out
      in a typical urban area of Beijing from March 2014 to February 2015, using an
      AirmoVOC online analyzer. Based on the analysis of the ambient level and
      variation characteristics of isoprene, alpha-pinene and beta-pinene, the chemical
      reactivity was studied, and their sources were identified. Results showed that
      the concentrations of isoprene, alpha-pinene and beta-pinene in the urban area of
      Beijing were lower than those in richly vegetated areas; the concentrations of
      isoprene were at a moderate level compared with those of previous studies of
      Beijing. Concentrations of isoprene, alpha-pinene and beta-pinene showed
      different seasonal, monthly, daily and diurnal variations, and all of the three
      species showed higher level at night than those in the daytime as a whole, the
      variations of isoprene, alpha-pinene and beta-pinene mainly influenced by
      emission of sources, photochemical reaction, and meteorological parameters.
      Isoprene was the largest contributor to the total OFP values than alpha-pinene
      and beta-pinene. alpha-Pinene was the largest contributor to the total SOAFP
      values than isoprene and beta-pinene in autumn, while isoprene was the largest
      one in other seasons. Isoprene, alpha-pinene and beta-pinene were derived mainly
      from biological sources; and alpha-pinene level were also affected by industrial
      sources. To reduce the concentrations of isoprene, alpha-pinene and beta-pinene,
      it is necessary to scientifically select urban green plant species, and more
      strict control measures should be taken to reduce the emission of alpha-pinene
      from industrial sources, such as artificial flavors and resins synthesis
      processes.

PMID- 30195675
TI  - Chemical characterization of fine and ultrafine PM, direct and indirect
      genotoxicity of PM and their organic extracts on pulmonary cells.
AB  - Particulate matter in ambient air constitutes a complex mixture of fine and
      ultrafine particles composed of various chemical compounds including metals,
      ions, and organics. A multidisciplinary approach was developed by studying
      physico-chemical characteristics and mechanisms involved in the toxicity of
      particulate atmospheric pollution. PM0.3-2.5 and PM2.5 including ultrafine
      particles were sampled in Dunkerque, a French industrialized seaside city. PM
      samples were characterized from a chemical and toxicological point of view.
      Physico-chemical characterization evidenced that PM2.5 comes from several
      sources: natural ones, such as soil resuspension and marine sea-salt emissions,
      as well as anthropogenic ones, such as shipping traffic, road traffic, and
      industrial activities. Human BEAS-2B lung cells were exposed to PM0.3-2.5, or to
      the Extractable Organic Matter (EOM) of PM0.3-2.5 and PM2.5. These exposures
      induced several mechanisms of action implied in the genotoxicity, such as
      oxidative DNA adducts and DNA Damage Response. The toxicity of PM-EOM was higher
      for the sample including the ultrafine fraction (PM2.5) containing also higher
      concentrations of polycyclic aromatic hydrocarbons. These results evidenced the
      major role of organic compounds in the toxicity of PM.

PMID- 30195676
TI  - Chemical characteristics of haze particles in Xi'an during Chinese Spring
      Festival: Impact of fireworks burning.
AB  - Fireworks burning releases massive fine particles and gaseous pollutants,
      significantly deteriorating air quality during Chinese Lunar New Year (LNY)
      period. To investigate the impact of the fireworks burning on the atmospheric
      aerosol chemistry, 1-hr time resolution of PM2.5 samples in Xi'an during the
      winter of 2016 including the LNY were collected and detected for inorganic ions,
      acidity and liquid water content (LWC) of the fine aerosols. PM2.5 during the LNY
      was 167+/-87MUg/m3, two times higher than the China National Ambient Air Quality
      Standard (75MUg/m3). K+ (28wt.% of the total ion mass) was the most abundant ion
      in the LNY period, followed by SO42- (25wt.%) and Cl- (18wt.%). In contrast, NO3-
      (34wt.%) was the most abundant species in the haze periods (hourly
      PM2.5>75MUg/m3), followed by SO42- (29.2wt.%) and NH4+ (16.3wt.%), while SO42 -
      (35wt.%) was the most abundant species in the clean periods (hourly
      PM2.5<75MUg/m3), followed by NO3- (23.1wt.%) and NH4+ (11wt.%). Being different
      from the acidic nature in the non-LNY periods, aerosol in the LNY period
      presented an alkaline nature with a pH value of 7.8+/-1.3. LWC during the LNY
      period showed a robust linear correlation with K2SO4 and KCl, suggesting that
      aerosol hygroscopicity was dominated by inorganic salts derived from fireworks
      burning. Analysis of correlations between the ratios of NO3-/SO42- and NH4+/SO42-
      indicated that heterogeneous reaction of HNO3 with NH3 was an important formation
      pathway of particulate nitrate and ammonium during the LNY period.

PMID- 30195677
TI  - Size distribution and source of heavy metals in particulate matter on the lead
      and zinc smelting affected area.
AB  - In order to understand the size distribution and the main kind of heavy metals in
      particulate matter on the lead and zinc smelting affected area, particulate
      matter (PM) and the source samples were collected in Zhuzhou, Hunan Province from
      December 2011 to January 2012 and the results were discussed and interpreted.
      Atmospheric particles were collected with different sizes by a cascade impactor.
      The concentrations of heavy metals in atmospheric particles of different sizes,
      collected from the air and from factories, were measured using an inductively
      coupled plasma mass spectrometry (ICP-MS). The results indicated that the average
      concentration of PM, chromium (Cr), arsenic (As), cadmium (Cd) and lead (Pb) in
      PM was 177.3 +/- 33.2 MUg/m3, 37.3 +/- 8.8 ng/m3, 17.3 +/- 8.1 ng/m3, 4.8 +/- 3.1
      ng/m3 and 141.6 +/- 49.1 ng/m3, respectively. The size distribution of PM
      displayed a bimodal distribution; the maximum PM size distribution was at 1.1-2.1
      MUm, followed by 9-10 MUm. The size distribution of As, Cd and Pb in PM was
      similar to the distribution of the PM mass, with peaks observed at the range of
      1.1-2.1 MUm and 9-10 MUm ranges while for Cr, only a single-mode at 4.7-5.8 MUm
      was observed. PM (64.7%), As (72.5%), Cd (72.2%) and Pb (75.8%) were associated
      with the fine mode below 2.1 MUm, respectively, while Cr (46.6%) was associated
      with the coarse mode. The size distribution characteristics, enrichment factor,
      correlation coefficient values, source information and the analysis of source
      samples showed that As, Cd and Pb in PM were the typical heavy metal in lead and
      zinc smelting affected areas, which originated mainly from lead and zinc smelting
      sources.

PMID- 30195678
TI  - Influences of accumulated mileage and technological changes on emissions of
      regulated pollutants from gasoline passenger vehicles.
AB  - In this study, the influences of accumulated mileage (deterioration) and
      technological changes (emission standards) on emission factors (EFs) of regulated
      pollutants (CO, HC, and NOx) from gasoline passenger vehicles were investigated
      based on Inspection and Maintenance (I/M) data using the chassis dynamometer
      method. The accumulated mileage of passenger vehicles was significantly linearly
      correlated with vehicle age. For most cases, the average EFs of CO, HC and NOx
      were significantly linearly correlated with accumulated mileage, indicating that
      emission deterioration had a significant impact on pollutant EFs. Implemented
      emission standards markedly influenced the EFs of regulated pollutants, and EFs
      markedly decreased with progressing emission standards. The present study also
      compared EFs of regulated pollutants between this study and the International
      vehicle emission (IVE) model, and marked differences in EFs were seen with
      variations in emission standards, vehicle types and accumulated mileage; NOx EFs
      in this study were higher than in the IVE model. The results provide new insight
      into estimating regulated pollutant emissions using the IVE model.

PMID- 30195679
TI  - Fog composition along the Yangtze River basin: Detecting emission sources of
      pollutants in fog water.
AB  - To investigate the fog chemistry along the Yangtze River basin, a field
      observation experiment was performed from Shanghai to Wuhan during November 2015.
      Fifteen fog water samples were collected by using a three-stage Caltech Active
      Strand Cloud water Collector (CASCC). The three-stage CASCC was mounted on the
      board of a ship. PH, electrical conductivity (EC), H2O2, HCHO, S(IV), ten
      inorganic ions, seven organicacids and sixteen trace metal elements were measured
      in this study. The pH of fog water samples ranged from weakly acidic (pH4.3) to
      weakly alkaline (pH7.05) and the EC ranged from 32.4 to 436.3MUS/cm. The main
      cations in fog water were NH4+ and Ca2+, accounting for 12.35% and 29.07% of
      those inorganic ions, respectively. In addition, SO42- and NO3- contributed to
      25.52% and 12.93% to total anion concentrations respectively. Moreover, the
      dominant kinds of organicacids were formate and oxalate, occupying 45.28% and
      28.03% of the total organicacids, respectively. For trace metal elements in fog
      samples, Al, Fe, Zn, and Ba revealed 34.6%, 16.4%, 19.3%, and 20.9% contributions
      to these sixteen trace element concentrations, respectively. The results
      indicated that pollutants were mainly from human activities, including fossil
      fuel combustion, biomass burning, steel-making, stone quarrying and sand digging.
      Besides, natural sources including natural background levels and long-range
      transport of sea salt particles also aggravated the pollution levels in the fog
      events along the Yangtze River.

PMID- 30195680
TI  - Long-term observations of tropospheric NO2, SO2 and HCHO by MAX-DOAS in Yangtze
      River Delta area, China.
AB  - Yangtze River Delta (YRD) area is one of the important economic zones in China.
      However, this area faces increasing environmental problems. In this study, we use
      ground-based multi-axis differential optical absorption spectroscopy (MAX-DOAS)
      network in Eastern China to retrieve variations of NO2, SO2, and formaldehyde
      (HCHO) in the YRD area. Three cities of YRD (Hefei, Nanjing, and Shanghai) were
      selected for long-term observations. This paper presents technical performance
      and characteristics of instruments, their distribution in YRD, and results of
      vertical column densities (VCDs) and profiles of NO2, SO2, and HCHO. Average
      diurnal variations of tropospheric NO2 and SO2 in different seasons over the
      three stations yielded minimum values at noon or in the early afternoon, whereas
      tropospheric HCHO reached the maximum during midday hours. Slight reduction of
      the pollutants in weekends occurred in all the three sites. In general trace gas
      concentrations gradually reduced from Shanghai to Hefei. Tropospheric VCDs of
      NO2, SO2, and HCHO were compared with those from Ozone Monitoring Instrument
      (OMI) satellite observations, resulting in R2 of 0.606, 0.5432, and 0.5566,
      respectively. According to analysis of regional transports of pollutants,
      pollution process happened in YRD under the north wind with the pollution
      dissipating in the southeast wind. The feature is significant in exploring
      transport of tropospheric trace gas pollution in YRD, and provides basis for
      satellite and model validation.

PMID- 30195681
TI  - Characterization and acid-mobilization study for typical iron-bearing clay
      mineral.
AB  - In this study, iron speciation in five standard clay samples was characterized.
      Iron mobilization from these clays was then measured in acidic media. For
      comparison, a commercially available Arizona test dust (ATD) was also observed.
      The results showed that the free-Fe contents of clays were commonly lower than
      that of dust aerosols. The components of clays were dominant by the structural Fe
      held in the aluminosilicate lattice. The iron solubility of the clays were in the
      order of KGa-2 > SWy-2 > CCa-2 > IMt-2 > NAu-2. Based upon the Mossbauer spectrum
      and transmission electron microscopy (TEM) analysis, the Fe(II) fraction and the
      Fe/Si ratio of clay particles changed after dissolution, suggesting the total Fe
      solubility depended on the Fe atom states existing within the aluminosilicate
      lattice. The Fe in KGa-2 and SWy-2 was most likely substituted for alkaline
      elements as the interlayer ions held by ionic bonds in the aluminosilicate, which
      are more liable to dissolution. However, the Fe in NAu-2 was more likely to be
      bound by strong covalent bonds in aluminosilicate mineral, which is less soluble.
      The much highly soluble Fe in ATD was not only linked to the dissolution of an
      appreciable fraction of Fe(II), but also could be attributed to the fact that the
      Fe bonds in the clay fraction of ATD were mainly present as ionic bonds. The TEM
      images showed that reacted clay particles displayed less aggregate particles,
      with nanoparticle aggregates and the Fe/S-rich tiny particles attached to the
      remains.

PMID- 30195682
TI  - Observation and analysis of atmospheric volatile organic compounds in a typical
      petrochemical area in Yangtze River Delta, China.
AB  - Volatile organic compounds (VOCs) are a kind of important precursors for ozone
      photochemical formation. In this study, VOCs were measured from November 5th,
      2013 to January 6th, 2014 at the Second Jinshan Industrial Area, Shanghai, China.
      The results showed that the measured VOCs were dominated by alkanes (41.8%),
      followed by aromatics (20.1%), alkenes (17.9%), and halo-hydrocarbons (12.5%).
      The daily trend of the VOC concentration showed a bimodal feature due to the rush
      hour traffic in the morning and at nightfall. Based on the VOC concentration, a
      receptor model of Positive Matrix Factorization (PMF) coupled with the
      information related to VOC sources was applied to identify the major VOC
      emissions. The result showed five major VOC sources: solvent use and industrial
      processes were responsible for about 30% of the ambient VOCs, followed by rubber
      chemical industrial emissions (23%), refinery and petrochemical industrial
      emissions (21%), fuel evaporations (13%) and vehicular emissions (13%). The
      contribution of generalized industrial emissions was about 74% and significantly
      higher than that made by vehicle exhaust. Using a propylene-equivalent method,
      alkenes displayed the highest concentration, followed by aromatics and alkanes.
      Based on a maximum incremental reactivity (MIR) method, the average hourly ozone
      formation potential (OFP) of VOCs is 220.49 ppbv. The most significant source for
      ozone chemical formation was identified to be rubber chemical industrial
      emissions, following one by vehicular emission. The data shown herein may provide
      useful information to develop effective VOC pollution control strategies in
      industrialized area.

PMID- 30195683
TI  - Understanding unusually high levels of peroxyacetyl nitrate (PAN) in winter in
      Urban Jinan, China.
AB  - Peroxyacetyl nitrate (PAN), as a major secondary pollutant, has gained increasing
      worldwide attentions, but relevant studies in China are still quite limited.
      During winter of 2015 to summer of 2016, the ambient levels of PAN were measured
      continuously by an automatic gas chromatograph equipped with an electron capture
      detector (GC-ECD) analyzer at an urban site in Jinan (China), with related
      parameters including concentrations of O3, NO, NO2, PM2.5, HONO, the photolysis
      rate constant of NO2 and meteorological factors observed concurrently. The mean
      and maximum values of PAN concentration were (1.89 +/- 1.42) and 9.61 ppbv
      respectively in winter, and (2.54 +/- 1.44) and 13.47 ppbv respectively in
      summer. Unusually high levels of PAN were observed during severe haze episodes in
      winter, and the formation mechanisms of them were emphatically discussed. Study
      showed that high levels of PAN in winter were mainly caused by local accumulation
      and strong photochemical reactions during haze episodes, while mass transport
      played only a minor role. Accelerated photochemical reactions (compared to winter
      days without haze) during haze episodes were deduced by the higher concentrations
      but shorter lifetimes of PAN, which was further supported by the sufficient solar
      radiation in the photolysis band along with the high concentrations of precursors
      (NO2, VOCs) and HONO during haze episodes. In addition, significant PAN
      accumulation during calm weather of haze episodes was verified by meteorological
      data.

PMID- 30195684
TI  - Strong ozone production at a rural site in theNorth China Plain: Mixed effects of
      urban plumesand biogenic emissions.
AB  - Regional ozone (O3) pollution has drawn increasing attention in China over the
      recent decade, but the contributions from urban pollution and biogenic emissions
      have not been clearly elucidated. To better understand the formation of the
      regional O3 problem in the North China Plain (NCP), intensive field measurements
      of O3 and related parameters were conducted at a rural site downwind of Ji'nan,
      the capital city of Shandong province, in the summer of 2013. Markedly severe O3
      pollution was recorded, with the O3 mixing ratios exceeding the Chinese national
      ambient air quality standard on 28 days (a frequency of 78%) and with a maximum
      hourly value of 198 ppbv. Extensive regional transport of well-processed urban
      plumes to the site was identified. An observation-constrained chemical box model
      was deployed to evaluate in situ photochemical O3 production on two episodes. The
      results show that the in situ formation accounted for approximately 46% of the
      observed O3 accumulation, while the remainder (~54%) was contributed by regional
      transport of the O3-laden urban plumes. The in situ ozone production was in a
      mixed controlled regime that reducing either NOx or VOCs would lead to a
      reduction of ozone formation. Biogenic VOCs played an important role in the local
      ozone formation. This study demonstrates the significant mixed effects of both
      anthropogenic pollution from urban zones and biogenic emission in rural areas on
      the regional O3 pollution in the NCP region, and may have general applicability
      in facilitating the understanding of the formation of secondary pollution over
      China.

PMID- 30195685
TI  - Kinetic and product studies of Cl atoms reactions with a series of branched
      Ketones.
AB  - The rate constants for the Cl atom reaction with three branched ketones have been
      measured at 298+/-2K and 760Torr using the relative rate method in the absence of
      NO. The rate constants values obtained (in units of 10-10cm3/(molecule.sec)) are:
      k(2-methyl-3-pentanone)=1.07+/-0.26, k(3-methyl-2-pentanone)=1.21+/-0.26, and k(4
      methyl-2-pentanone)=1.35+/-0.27. Combining the chemical kinetic data obtained by
      this study with those reported for other ketones, a revised Structure Activity
      Relationship (SAR) parameter and R group reactivity (kR) of R(O)R' and CHx (x=1,
      2, 3) group reactivity (kCHx) toward Cl atoms were proposed. In addition, the
      products from the three reactions in the presence of NO were also identified and
      quantified by using PTR-ToF-MS and GC-FID, and the yields of the identified
      products are: acetone (39%+/-8%)+ethanal (78%+/-12%), 2-butanone (22%+/
      2%)+ethanal (75%+/-10%)+propanal (14%+/-1%) and acetone (26%+/-3%)+2
      methylpropanal (24%+/-2%), for Cl atoms reaction with 2-methyl-3-pentanone, 3
      methyl-2-pentanone and 4-methyl-2-pentanone, respectively. Based on the obtained
      results, the reaction mechanisms of Cl atoms with these three ketones are
      proposed.

PMID- 30195686
TI  - Pollution characteristics of atmospheric dustfall and heavy metals in a typical
      inland heavy industry city in China.
AB  - Through field sampling of atmospheric dustfall in regions of Zhuzhou City, China
      for a period of one year, the deposition fluxes of atmospheric dustfall and five
      heavy metals contained inside, including Cr, As, Cd, Hg and Pb, were analyzed.
      Meanwhile the enrichment factor and index methods were used to analyze the
      pollution characteristics of heavy metals of atmospheric dustfall in Zhuzhou. The
      annual deposition flux of atmospheric dustfall in Zhuzhou was 50.79 g/(m2.year),
      while the annual deposition fluxes of Cr, As, Cd, Hg and Pb were 9.80, 59.69,
      140.09, 0.87 and 1074.91 mg/(m2.year), respectively. The pollution level of
      atmospheric dustfall in Zhuzhou was relatively lower compared with most other
      cities in China, but the deposition fluxes of As, Cd, Hg and Pb in atmospheric
      dustfall in Zhuzhou were much higher than that in most cities and regions around
      the world. Cd is the typical heavy metal element in atmospheric dustfall in
      Zhuzhou, and both the enrichment factor and pollution index of Cd were the
      highest. Cd, Hg, Pb and As in atmospheric dustfall were mainly from human
      activities. According to the single-factor index, Nemerow index and pollution
      load index analyses, the atmospheric dustfall in Zhuzhou could easily cause
      severe heavy metal pollution to urban soil, and the most polluting element was
      Cd, followed by Pb, As and Hg. Only the pollution level of Cr lay in the safety
      region and mainly originated from natural sources.

PMID- 30195687
TI  - Kinetic study of the gas-phase reaction of O3 with three unsaturated alcohols.
AB  - Rate constants for the reactions of ozone with 1-octen-3-ol, 1-nonen-3-ol and 1
      nonen-4-ol have been determined at 298+/-1K and atmospheric pressure for the
      first time. The experiments were performed in a 100-L FEP Teflon film bag using
      absolute rate method; the rate constants were (1.91+/-0.19)*10-17, (1.89+/
      0.20)*10-17, and (0.83+/-0.08)*10-17cm3/(molecule.sec) for 1-octen-3-ol, 1-nonen
      3-ol, and 1-nonen-4-ol, respectively. The rate constants have been compared with
      those of unsaturated alcohols structural homologs, and used to estimate the
      reaction reactivity. The electronegativity of carbon-carbon double bond was
      calculated by atomic charges analysis. The calculated results show that the
      electronic effect of the lone pair electrons of hydroxyl oxygen is the main cause
      of the difference in rate coefficient. According to the obtained rate constants,
      the atmospheric lifetimes of studied unsaturated alcohols were also estimated,
      which indicates that the reaction with ozone is an important loss pathway in the
      atmosphere, especially in polluted areas.

PMID- 30195688
TI  - Seasonal variation and size distribution of biogenic secondary organic aerosols
      at urban and continental background sites of China.
AB  - Size-resolved biogenic secondary organic aerosols (BSOA) derived from isoprene
      and monoterpene photooxidation in Qinghai Lake, Tibetan Plateau (a continental
      background site) and five cities of China were measured using gas
      chromatography/mass spectrometry (GC/MS). Concentrations of the determined BSOA
      are higher in the cities than in the background and are also higher in summer
      than in winter. Moreover, strong positive correlations (R2=0.44-0.90) between
      BSOA and sulfate were found at the six sites, suggesting that anthropogenic
      pollution (i.e., sulfate) could enhance SOA formation, because sulfate provides a
      surface favorable for acid-catalyzed formation of BSOA. Size distribution
      measurements showed that most of the determined SOA tracers are enriched in the
      fine mode (<3.3MUm) except for cis-pinic and cis-pinonic acids, both presented a
      comparable mass in the fine and coarse (>3.3MUm) modes, respectively. Mass ratio
      of oxidation products derived from isoprene to those from monoterpene in the five
      urban regions during summer are much less than those in Qinghai Lake region. In
      addition, in the five urban regions relative abundances of monoterpene oxidation
      products to SOA are much higher than those of isoprene. Such phenomena suggest
      that BSOA derived from monoterpenes are more abundant than those from isoprene in
      Chinese urban areas.

PMID- 30195689
TI  - Characterization of coal burning-derived individual particles emitted from an
      experimental domestic stove.
AB  - Coal combustion in the domestic stoves, which is common in most parts of the
      Chinese countryside, can release harmful substances into the air and cause health
      issues. In this study, particles emitted from laboratory stove combustion of the
      raw powder coals were analyzed for morphologies and chemical compositions by
      using transmission electron microscopy (TEM) coupled with energy-dispersive X-ray
      spectrometry (EDX). The coal burning-derived individual particles were classified
      into two groups: carbonaceous particles (including soot aggregates and organic
      particles) and non-carbonaceous particles (including sulfate, mineral and metal
      particles). The non-carbonaceous particles, which constituted a majority of the
      coal burning-derived emissions, were subdivided into Si-rich, S-rich, K-rich, Ca
      rich, and Fe-rich particles according to the elemental compositions. The Si-rich,
      S-rich and K-rich particles are commonly observed in the coal burning emission.
      The proportions for particles of different types exhibit obvious coal-issue
      dependence. Burning of coal with high ash yield could emit more non-carbonaceous
      particles, and burning of coal with high sulfur content can emit more S-rich
      particles. By comparing the S-rich particles from this coal burning experiment
      with those in the atmosphere, we draw a conclusion that some S-rich particles in
      the atmosphere in China could be mainly sourced from coal combustion.

PMID- 30195690
TI  - Influence of ship emissions on NOx, SO2, O3 and PM concentrations in a North-Sea
      harbor in France.
AB  - The influence of in-port ship emissions on gases and PM10 concentrations has been
      estimated in the port city of Calais, northern France, one of the busiest harbor
      in Europe, with numerous rotations of ferries or roll-on/roll-off cargo in
      average per day. NOx, SO2, O3 and PM10 concentrations were continuously measured
      over a three-month period, as well as real-time particle size distribution. A
      rural site located at Cape Gris-Nez, 20km from Calais, was considered to deduce
      intrinsic contribution of ship emissions at the harbor city. The average
      concentrations of the studied species as well as the pattern of the conditional
      bivariate probability function at the two sites evidenced that in-port shipping,
      especially during the maneuvering operations, has an important influence on the
      NOx and SO2 concentrations. The impact of shipping in the harbor of Calais on
      average concentrations was estimated to 51% for SO2, 35% for NO, 15% for NO2 and
      2% for PM10 in the studied period. Concentration peaks of SO2 and NOx associated
      with an O3 depletion appeared synchronized with departures and arrivals of
      ferries. For winds blowing from the harbor, when compared to the background
      level, the number of particles appeared 10 times higher, with the highest
      differences in the 30-67nm and the 109-167nm size ranges. The average impact of
      in-port ships on PM10 concentrations was estimated to +28.9MUg/m3 and concerned
      mainly the PM1 size fraction (40%). Punctually, PM10 can potentially reach a
      concentration value close to 100MUg/m3.

PMID- 30195691
TI  - Are current Chinese national ambient air quality standards on 24-hour averages
      for particulate matter sufficient to protect public health?
AB  - With rapid economic development and urbanization in recent decades, China has
      experienced the worsening of ambient air quality. For better air quality
      management to protect human health, Chinese government revised national ambient
      air quality standards (NAAQS) for particulate matter (PM) in 2012 (GB3095-2012).
      To assess the effectiveness of current NAAQS for PM on public health in Chinese
      population, we conducted a meta-analysis on published studies examining the
      mortality risk of short-term exposure to PM with aerodynamic diameters less than
      10 and 2.5MUm (PM10 and PM2.5) in China. The reported 24-hour concentrations of
      PM10 and PM2.5 in studies ranged from 43.5 to 150.1MUg/m3 and 37.5 to
      176.7MUg/m3. In the pooled excess, mortality risk estimates of short-term
      exposure to PM. In specific, per 10MUg/m3 increase in PM10, we observed increases
      of 0.40% (95%CI: 0.33%, 0.47%), 0.57% (95%CI: 0.44%, 0.70%) and 0.49% (95%CI:
      0.40%, 0.58%) in total, respiratory and cardiovascular mortality, per 10MUg/m3
      increase in PM2.5, we observed increases of 0.51% (95%CI: 0.38%, 0.63%), 0.62%
      (95%CI: 0.52%, 0.73%) and 0.75% (95%CI: 0.54%, 0.95%) in total, respiratory and
      cardiovascular mortality. Finally, we derived 125MUg/m3 for PM10 and 62.5MUg/m3
      for PM2.5 as 24-hour recommendation values based on the pooled estimates. Our
      results indicated that current Chinese NAAQS for PM could be sufficient in
      mitigating the excess mortality risk from short-term exposure to ambient PM.
      However, future research on long-term exposure cohort studies in Chinese
      population is also essential in revising annual averages for PM in Chinese NAAQS.

PMID- 30195692
TI  - Fast screening compositions of PM2.5 by ATR-FTIR: Comparison with results from IC
      andOC/EC analyzers.
AB  - Chemical speciation of fine particles or PM2.5 collected on filters is still a
      costly and time-consuming task. In this study, filter-based PM2.5 samples were
      collected during November-December 2013 at four sites in Guangzhou, and the major
      components were fast screened (~7min per filter sample) by Attenuated Total
      Reflectance (ATR)-Fourier Transform Infrared Spectroscopic (FTIR) in comparison
      with that measured by Organic carbon/Element carbon (OC/EC) analyzer and Ion
      Chromatography (IC). The concentrations of nitrate, ammonium, sulfate, primary
      organic carbon (POC) and secondary organic carbon (SOC) measured by OC/EC and IC
      analyzers were better correlated with their infrared absorption peak heights at
      1320cm-1 for nitrate, 1435, 3045 and 3215cm-1 for ammonium, 615cm-1 for sulfate,
      690, 760 and 890cm-1 for POC and 1640 and 1660cm-1 for SOC respectively, during
      polluted days (PM2.5>75MUg/m3) than during clean days (PM2.5<=75MUg/m3). With the
      evolution of a haze episode during our field campaign, the concentrations of the
      major PM2.5 components displayed consistent variations with their infrared
      absorption peak heights, suggesting ATR-FTIR could be a fast and useful technique
      to characterize filter-based PM2.5 compositions particularly during pollution
      events although cautions should be taken when PM2.5 levels are low. Notably,
      elevated PM2.5 mass concentrations occurred with enhanced ratios of [NO3-]/[SO42
      ] and [NH4+]/[SO42-], implying that nitrogenous components play vital roles in
      the PM2.5 pollution events in the study region.

PMID- 30195693
TI  - Role of water on the H-abstraction from methanol by ClO.
AB  - The influence of a single water molecule on the reaction mechanism and kinetics
      of hydrogen abstraction from methanol (CH3OH) by the ClO radical has been
      investigated using ab initio calculations. The reaction proceeds through two
      channels: abstraction of the hydroxyl H-atom and methyl H-atom of CH3OH by ClO,
      leading to the formation of CH3O+HOCl (+H2O) and CH2OH+HOCl (+H2O), respectively.
      In both cases, pre- and post-reactive complexes were located at the entrance and
      exit channel on the potential energy surfaces. Results indicate that the
      formation of CH2OH+HOCl (+H2O) is predominant over the formation of CH3O+HOCl
      (+H2O), with ambient rate constants of 3.07*10-19 and 3.01*10
      23cm3/(molecule.sec), respectively, for the reaction without water. Over the
      temperature range 216.7-298.2K, the presence of water is seen to effectively
      lower the rate constants for the most favorable pathways by 4-6 orders of
      magnitude in both cases. It is therefore concluded that water plays an inhibitive
      role on the CH3OH+ClO reaction under tropospheric conditions.

PMID- 30195694
TI  - Effect of relative humidity and the presence of aerosol particles on the alpha
      pinene ozonolysis.
AB  - The alpha-pinene ozonolysis under the different environmental conditions were
      observed in a smog chamber. The second-order rate constant (k) was determined to
      be (7.25+/-0.06)*10-17cm3/(molecule.sec) under 20% of relative humidity (RH) and
      room temperature. RH showed a marked influence on the alpha-pinene ozonolysis.
      The value of k increased with RH increase, which was 1.6 times faster at RH=80%
      than that at RH=20%. Additionally, the value of k apparently changed in the
      presence of the aerosol particles. The diesel soot increased the k value. The fly
      ash prohibited the reaction, however, H2SO4-treated fly ash promoted the
      reaction. The information of products gained using FT-IR and SPAMS showed that
      pinonic acid, 10-hydroxy-pinonic acid and pinic acid could be generated during
      the alpha-pinene ozonolysis. Water molecules could take part in the formation of
      the products, and play a vital role in the degradation of alpha-pinene. The
      atmospheric residence time calculation showed that the ozonolysis in the
      atmosphere is an important way of the alpha-pinene consumption as compared to
      that reacted with OH during daytime. The results suggested that the degradation
      of alpha-pinene via the ozonization in the atmosphere may be affected greatly by
      RH, as well as the presence of aerosol particles. The ozonolysis reaction may be
      an important way of the alpha-pinene consumption during daytime.

PMID- 30195695
TI  - Localised non-viral delivery of nucleic acids for nerve regeneration in injured
      nervous systems.
AB  - Axons damaged by traumatic injuries are often unable to spontaneously regenerate
      in the adult central nervous system (CNS). Although the peripheral nervous system
      (PNS) has some regenerative capacity, its ability to regrow remains limited
      across large lesion gaps due to scar tissue formation. Nucleic acid therapy holds
      the potential of improving regeneration by enhancing the intrinsic growth ability
      of neurons and overcoming the inhibitory environment that prevents neurite
      outgrowth. Nucleic acids modulate gene expression by over-expression of neuronal
      growth factor or silencing growth-inhibitory molecules. Although in vitro
      outcomes appear promising, the lack of efficient non-viral nucleic acid delivery
      methods to the nervous system has limited the application of nucleic acid
      therapeutics to patients. Here, we review the recent development of efficient non
      viral nucleic acid delivery platforms, as applied to the nervous system,
      including the transfection vectors and carriers used, as well as matrices and
      scaffolds that are currently used. Additionally, we will discuss possible
      improvements for localised nucleic acid delivery.

PMID- 30195696
TI  - Pretreatment and hydrolysis of lignocellulosic wastes for butanol production:
      Challenges and perspectives.
AB  - Butanol is acknowledged as a drop-in biofuel that can be used in the existing
      transportation infrastructure, addressing the needs for sustainable liquid fuel.
      However, before becoming a thoughtful alternative for fossil fuel, butanol should
      be produced efficiently from a widely-available, renewable, and cost-effective
      source. In this regard, lignocellulosic materials, the main component of organic
      wastes from agriculture, forestry, municipalities, and even industries seems to
      be the most promising source. The butanol-producing bacteria, i.e., Clostridia
      sp., can uptake a wide range of hexoses, pentoses, and oligomers obtained from
      hydrolysis of cellulose and hemicellulose content of lignocelluloses. The present
      work is dedicated to reviewing different processes containing pretreatment and
      hydrolysis of hemicellulose and cellulose developed for preparing fermentable
      hydrolysates for biobutanol production.

PMID- 30195697
TI  - Applications of membrane bioreactors for water reclamation: Micropollutant
      removal, mechanisms and perspectives.
AB  - Membrane bioreactors (MBRs) have attracted attention in water reclamation as a
      result of the recent technical advances and cost reduction in membranes. However,
      the increasing occurrence of micropollutants in wastewaters has posed new
      challenges. Therefore, we reviewed the current state of research to identify the
      outstanding needs in this field. In general, the fate of micropollutants in MBRs
      relates to sorption, biodegradation and membrane separation processes.
      Hydrophobic, nonionized micropollutants are favorable in sorption, and the
      biological degradation shows higher efficiency at relatively long SRTs (30-40
      days) and HRTs (20-30 h), as a result of co-metabolism, metabolism and/or ion
      trapping. Although the membrane rejection rates for micropollutants are generally
      minor, final water quality can be improved via combination with other
      technologies. This review highlights the challenges and perspectives that should
      be addressed to facilitate the extended use of MBRs for the removal of
      micropollutants in water reclamation.

PMID- 30195698
TI  - Low Testosterone Level as a Predictor of Poststroke Emotional Disturbances: Anger
      Proneness and Emotional Incontinence.
AB  - BACKGROUND: The role of sex hormones in poststroke mood and emotional
      disturbances is unclear. We aimed to evaluate the impact of sex hormones on
      poststroke emotional disturbance, especially anger proneness (AP) and emotional
      incontinence (EI). We also investigated whether statins, which are widely used
      for stroke prevention, affect sex hormone levels or the presence of poststroke
      AP/EI based on the hypothesis that intensive treatment with statins would inhibit
      the synthesis of cholesterol, the preferred substrate of testosterone. METHODS:
      We prospectively enrolled 40 patients who experienced ischemic stroke at least 3
      months prior to study enrollment. We performed clinical and laboratory
      evaluations, including hormone-level measurements and neuropsychological tests.
      Poststroke AP and EI were assessed using interviews, then patients were divided
      into 2 groups: AP/EI-present or absent. RESULTS: Of the 40 patients (30 men, mean
      age 58.8 years), 16 (40.0%) were classified as AP/EI-present group. AP/EI were
      not related to stroke severity or location; however, the testosterone level was
      significantly lower in patients with AP/EI than in those without AP/EI (2.1 +/-
      1.7 vs. 3.9 +/- 2.5 ng/mL, P = .023). After adjusting for potential confounding
      variables, low testosterone levels were a significant independent predictor of
      AP/EI (odds ratio .68, 95% confidence interval .49-.96, P = .027). In contrast,
      sex hormone levels and AP/EI prevalence did not differ between statin users and
      nonusers. CONCLUSIONS: AP/EI were associated with low testosterone levels in
      patients with previous ischemic stroke, but statin use did not affect AP/EI
      prevalence.

PMID- 30195699
TI  - MR imaging of vaginal cellular schwannoma.

PMID- 30195700
TI  - Comparison of cryosurvival and spermatogenesis efficiency of cryopreserved
      neonatal mouse testicular tissue between three vitrification protocols and
      controlled-rate freezing.
AB  - Grafting of cryopreserved testicular tissue is a promising tool for fertility and
      testicular function preservation in endangered species, mutant animals, or cancer
      patients for future use. In this study, we aimed to improve the whole neonatal
      mouse testicular tissue cryopreservation protocols by comparing cryosurvival,
      spermatogenesis, and androgen production of grafted testicular tissue after
      cryopreservation with three different vitrification protocols and an automated
      computed controlled-rate freezing. Whole neonatal mouse testes were vitrified
      with various vitrification solutions (V1) 40% EG + 18% Ficoll + 0.35 M Sucrose,
      (V2) DAP 213 (2 M DMSO + 1 M Acetamid + 3 M PG), or (V3) 15% EG + 15% PG + 0.5 M
      Sucrose (total solute concentration V1:74.34%, V2:44.0%, and V3:49.22% wt/vol).
      Alternatively, neonatal testicular tissue was also frozen in 0.7 M DMSO +5% fetal
      bovine serum using controlled-rate freezing and compared to fresh grafted
      testicular tissue, sham grafted controls, and the vitrification protocol groups.
      Fresh (n = 4) and frozen-thawed (n = 4) testes tissues were grafted onto the
      flank of castrated male NCr Nude recipient mouse. The grafts were harvested after
      three months. Fresh or frozen-thawed grafts with controlled-rate freezing had the
      highest rate of tissue survival compared to other vitrified protocols after
      harvesting (p < 0.05). Both controlled-rate freezing and V1 protocol groups
      displayed the most advanced stages of spermatogenesis with elongated spermatids
      and spermatozoa in 17.6 +/- 1.3% and 16.3 +/- 1.9% of seminiferous tubules based
      on histopathological evaluation, respectively. Hosts of the testicular graft from
      controlled-rate freezing had higher levels of serum testosterone compared to all
      other vitrified-thawed graft groups (p < 0.05). This study shows that completed
      spermatogenesis from whole neonatal mouse testes were obtained when frozen with
      controlled-rate freezing and V1 vitrification solution and that testicular
      cryopreservation efficacy vary with the protocol and vitrification technique.

PMID- 30195701
TI  - Vaccination Status and Other Preventive Measures in Medical Schools. Big Needs
      and Opportunities.
AB  - BACKGROUND: Proper immunization and knowledge in infection prevention are key
      factors in protecting medical students. AIM OF THE STUDY: To describe the status
      on vaccination recommended for healthcare workers (HCW) and infection prevention
      knowledge. METHODS: We conducted a cross-sectional study on medical students at
      clinical years of medical school from a public University in Mexico. RESULTS: A
      total of 1,824 medical students responded the survey. One thousand ninety (59.8%)
      were women. Median age was 22 years. One thousand six hundred twenty-two (88.9%)
      knew their childhood immunization status. One thousand seventy-one (58.7%) were
      vaccinated against influenza for the 2016-2017 season; 1667 (91.4%) had been
      vaccinated at least once against hepatitis B, only 315 (18.9%) of vaccinated had
      received a full course with 3 doses. Most students were vaccinated against
      measles, mumps and rubella during childhood, 542 (29.7%) received an additional
      dosage during or after adolescence. Six hundred ninety-seven (38.2%) were
      concerned about vaccine's safety. A total of 1,431 (78.5%) properly identified
      situations were standard precautions are recommended, and 1540 (84.4%) had
      received some training on safe care delivery and personal protective equipment.
      Regarding needle-stick injuries, 1165 (63.9%) had been informed on the protocols
      to follow if an injury occurred. Three hundred forty-nine (19.1%) had suffered
      needle-stick injuries, only 125 (35.8%) received immediate medical attention at
      the point of care. CONCLUSIONS: Most medical students were not vaccinated as
      recommended, and they were not adequately instructed on safe practices for
      medical attention, nor advised or followed when a health-care related accident
      occurs. The results may be useful for implementation strategies on vaccination
      compliance and training on infection prevention.

PMID- 30195702
TI  - Optimization of Routine Testing for MET Exon 14 Splice Site Mutations in NSCLC
      Patients.
AB  - INTRODUCTION: Genomic alterations affecting splice sites of MNNG HOS transforming
      gene (MET) exon 14 were recently identified in NSCLC patients. Objective
      responses to MET tyrosine kinase inhibitors have been reported in these patients.
      Thus, detection of MET exon 14 splice site mutations represents a major
      challenge. So far, most of these alterations were found by full-exome sequencing
      or large capture-based next-generation sequencing (NGS) panels, which are not
      suitable for routine diagnosis. METHODS: Aiming to provide a molecular testing
      method applicable in routine practice, we first developed a fragment-length
      analysis for detecting deletions in introns flanking MET exon 14. Second, we
      designed an optimized targeted NGS panel called CLAPv1, covering the MET exon 14
      and flanking regions in addition to the main molecular targets usually covered in
      genomic testing. In patients with MET exon 14 mutations, MET gene amplification,
      gene copy number and MET receptor expression were also determined. RESULTS: Among
      1514 formalin-fixed paraffin-embedded NSCLC samples, nonoptimized NGS allowed
      detection of MET exon 14 mutations in only 0.3% of the patients, and fragment
      length analysis detected deletions in 1.1% of the patients. Combined, the
      optimized CLAPv1 panel and fragment-length analysis implemented for routine
      molecular testing revealed MET exon 14 alterations in 2.2% of 365 additional
      NSCLC patients. MET gene amplification or high gene copy number was observed in 6
      of 30 patients (20%) harboring MET exon 14 mutations. CONCLUSIONS: These results
      show that optimized targeted NGS and fragment-length analysis improve detection
      of MET alterations in routine practice.

PMID- 30195703
TI  - Implications of the Eighth Edition of the TNM Proposal: Invasive Versus Total
      Tumor Size for the T Descriptor in Pathologic Stage I-IIA Lung Adenocarcinoma.
AB  - INTRODUCTION: The eighth edition of the TNM staging system included the proposal
      that the T descriptor be determined according to the invasive component,
      excluding lepidic component, for nonmucinous lung adenocarcinomas. We sought to
      conduct a clinicopathologic comparative analysis of the newly proposed
      classification using invasive size versus total tumor size. METHODS: Patients who
      underwent lung resection for primary lung adenocarcinoma with pathologic stage (p
      Stage) I-IIA (based on total size [t]) were reviewed (n = 1704). Pathologic
      invasive size was measured, and tumors were reclassified using invasive size (i).
      Cumulative incidence of recurrence and lung cancer-specific cumulative incidence
      of death were analyzed using a competing-risks approach. Prognostic
      discrimination by p-Stage(t) and p-Stage(i) was evaluated using a concordance
      index (C-index). RESULTS: The use of invasive size resulted in downstaging in 377
      of 1704 patients (22%), with twice as many patients with p-Stage IA1 (IA1[i]
      versus IA1[t]: 389 [23%] versus 195 [11%]). However, outcomes were similar
      between the two groups (IA1[i] versus IA1[t]: 5-year cumulative incidence of
      recurrence, 11% versus 13%; 5-year lung cancer-specific cumulative incidence of
      death, 5% versus 7%). Prognostic discrimination by p-Stage(i) was better than by
      p-Stage(t) (C-index for p-Stage[i] versus p-Stage[t]: recurrence, 0.614 versus
      0.593; lung cancer-specific death, 0.634 versus 0.621). CONCLUSIONS: When
      invasive size, rather than total size, was used for the T descriptor, a larger
      number of patients were classified with a favorable prognosis (p-Stage IA1) and
      better prognostic discrimination of p-Stage I-IIA nonmucinous lung
      adenocarcinomas was achieved.

PMID- 30195704
TI  - Treatment of Knee Meniscus Pathology: Rehabilitation, Surgery, and
      Orthobiologics.
AB  - The meniscal tear treatment paradigm traditionally begins with conservative
      measures such as physical therapy with referral for operative management for
      persistent or mechanical symptoms. As a result, the partial meniscectomy is
      performed more than any other orthopedic procedure in the United States. This
      treatment paradigm has shifted because the recent literature has supported the
      attempt to preserve or repair the meniscus whenever possible given its importance
      for the structural integrity of the knee joint and the risk of early
      osteoarthritis associated after meniscus excision. Choosing an appropriate
      management strategy depends on multiple factors such as patient demographics and
      location of the tear. Physical therapy remains a first-line treatment for knee
      pain secondary to meniscus tear and should be pursued in the setting of acute and
      chronic knee pain. Furthermore, there is a growing amount of evidence showing
      that elderly patients with complex meniscus tears in the setting of degenerative
      arthritis should not undergo arthroscopic surgery. Direct meniscus repair remains
      an option in ideal patients who are young, healthy, and have tears near the more
      vascular periphery of the meniscus but it is not suitable for all patients. Use
      of orthobiologics such as platelet-rich plasma and mesenchymal stem cells have
      shown promise in augmenting surgical repairs or as standalone treatments,
      although research for their use in meniscal tear management is limited.

PMID- 30195705
TI  - Frequency and Circumstances of Falls Reported by Ambulatory Unilateral Lower Limb
      Prosthesis Users: A Secondary Analysis.
AB  - BACKGROUND: More than 50% of lower limb prosthesis (LLP) users report falling at
      least once a year, placing them at high risk for adverse health outcomes such as
      decreased mobility and diminished quality of life. Efforts to decrease falls in
      LLP users have traditionally focused on developing clinical tests to assess fall
      risk, designing prosthetic components to improve patient safety, and identifying
      risk factors to recognize potential fallers. Little attention has been directed
      toward recording, reporting, and characterizing the circumstances of falls in LLP
      users. Identifying the most common types of falls could help guide and prioritize
      clinical and research needs. OBJECTIVE: To characterize the frequency and
      circumstances of falls reported by unilateral LLP users. DESIGN: Secondary
      analysis of data from 2 cross-sectional studies. SETTING: Outpatient clinic and
      research laboratory. PARTICIPANTS: Ambulatory unilateral transtibial and
      transfemoral LLP users (N = 66). INTERVENTION: None. OUTCOME: A fall-type
      classification framework was developed based on biomechanical theory and
      published falls terminology. Self-reported falls and accompanying narrative
      descriptions of LLP users' falls in the previous 12 months were analyzed with the
      framework. Frequencies, estimated proportions, and estimated counts were compared
      across fall circumstances using 95% confidence intervals. RESULTS: Thirty-eight
      participants (57.6%) reported 90 falls during the previous year. All reported
      falls were successfully categorized using the proposed framework. Most falls
      occurred from disruptions to the base of support, intrinsic destabilizing
      factors, and a diverse set of fall patterns. Walking on level terrain was the
      most common activity at the time of a fall. CONCLUSION: This secondary analysis
      showed that falls remain frequent in ambulatory LLP users and that clinicians and
      researchers might wish to prioritize falls owing to disruptions of the base of
      support that occur while walking. Additional research with a larger sample is
      required to confirm and expand these results. LEVEL OF EVIDENCE: III.

PMID- 30195706
TI  - A Descriptive Study of Self-Reported Injury in Non-elite Adaptive Athletes.
AB  - BACKGROUND: Adaptive sports programs are increasing across the country and there
      is a paucity of research investigating the epidemiology and sports injury risk
      factors in non-elite athletes. OBJECTIVE: To assess the demographics, training
      regime, and injuries incurred by adaptive athletes participating in local
      adaptive sports clubs and to assess the athletes' type of medical care and
      prevalence of those with spasticity. DESIGN: Descriptive cross-sectional study.
      SETTING: Local area adaptive sports teams and programs. PARTICIPANTS: Sixty-one
      athletes participating in wheelchair basketball, wheelchair rugby, sled hockey,
      and adaptive rowing were surveyed, with a response rate of 70.5%. INTERVENTIONS:
      Completion of self-report survey. OUTCOME: Report of injury prevalence, injury
      characteristics, type of medical care, and assessment of frequency and severity
      of spasticity using the Penn Spasm Frequency Scale. RESULTS: Most athletes (86%)
      trained or competed in their main sport 9-12 months per year. Most athletes
      (79.1%) trained at least 4 hours per week. In the past 12 months, 39.5% of
      athletes surveyed sustained an injury that required them to miss practice or a
      competition, with 58.8% of these athletes having sustained a significant injury.
      Many of those injured (64.7%) had never participated in an injury prevention or
      conditioning program. Injury prevalence by sport was 42.9% in wheelchair rugby,
      60% in sled hockey, 44% wheelchair basketball, and 0% in adaptive rowing. The
      most commonly injured body parts were the shoulder (52.9%) and wrist (52.9%).
      CONCLUSIONS: This study shows that non-elite adaptive sports athletes sustain
      similar types of injuries as noted in published reports of elite athletes but
      could be provided with less injury prevention education and access to medical
      care. This area will require future study, especially investigating injury risk
      factors within specific sports and diagnoses. LEVEL OF EVIDENCE: III.

PMID- 30195707
TI  - Bone Mineral Density Among Individuals With Residual Lower Limb Weakness After
      Polio.
AB  - BACKGROUND: Literature indicates that individuals with long-term residual lower
      extremity (LE) weakness after polio have decreased bone mineral density (BMD)
      deficiencies related to muscle weakness. Where weakness is asymmetrical, bone
      densitometry (BDt) measured only on the stronger LE may misclassify BMD.
      OBJECTIVE: To determine (1) whether femoral neck BMD differed from side to side
      in individuals with asymmetrical LE muscle weakness, and (2) the proportion of
      individuals at risk for underdiagnosis of low bone density or osteoporosis given
      unilateral assessment of the femoral neck. DESIGN: Retrospective study. SETTING:
      Outpatient postpolio center. PARTICIPANTS: Patients >18 years old with complete
      relevant data. MAIN OUTCOME MEASURES: BDt T scores, BMD categories based on
      standard T-score ranges, and side of LE weakness determined by a strength score.
      RESULTS: Forty-three subjects had at least 1 femoral neck T score and bilateral
      LE strength scores. Fourteen (32.5%) had BDt only on their weaker LE and 14
      (32.5%) had BDt only on their stronger LE. Of the 15 subjects with BDt done on
      both femoral necks, T scores (mean [standard deviation]) were lower in the weaker
      LE (-1.73 [1.09]) than the stronger LE (-0.88 [1.0]) (P = .001). Classification
      of low bone density or osteoporosis was more frequent based on T scores taken on
      a weaker LE (48.3% and 24.1%, respectively) than from T scores from a stronger LE
      (41.4% and 6.9%, respectively). CONCLUSIONS: In this small sample, using strong
      limb T scores resulted in fewer individuals categorized as having low bone
      density or osteoporosis than when weak-limb T scores were used. Underestimating
      BMD loss may lead to undertreatment and increased risk of morbidity, mortality,
      and costs associated with femoral neck fractures in this high-fall-risk group.
      LEVEL OF EVIDENCE: III.

PMID- 30195708
TI  - Ankle Joint and Rearfoot Biomechanics During Toe-In and Toe-Out Walking in People
      With Medial Compartment Knee Osteoarthritis.
AB  - BACKGROUND: Toe-in and toe-out walking are 2 strategies that have been shown to
      be effective in reducing the knee adduction moment in people with knee
      osteoarthritis. However, despite a positive biomechanical impact on the knee,
      altering foot rotation may impart unintended forces or joint positions on the
      ankle that could impact joint health. The kinematic and kinetic changes at the
      ankle during toe-in or toe-out walking have yet to be examined. OBJECTIVE: To
      examine ankle/rearfoot biomechanics during toe-in and toe-out walking in those
      with knee osteoarthritis. DESIGN: Single-session repeated measures design to
      compare ankle biomechanics during walking with 4 different foot rotations.
      SETTING: University motion analysis laboratory. PARTICIPANTS: A convenience
      sample (N = 15) of men and women with a diagnosis of medial knee osteoarthritis
      confirmed by radiographs. METHODS: Participants walked in 4 conditions guided by
      real-time biofeedback: (1) toe-in (+10 degrees ), (2) zero rotation (0 degrees ),
      (3) toe-out (-10 degrees ), and (4) toe-out (-20 degrees ). Ankle and rearfoot
      kinematics and kinetics were examined during barefoot over-ground walking. MAIN
      OUTCOME MEASURES: Ankle joint angles, moments, moment impulses, and foot
      rotation. RESULTS: Overall, toe-in compared to toe-out walking decreased (P =
      .03) peak rearfoot eversion (toe-in = -1.6 degrees ; 10 degrees  toe-out = -3.7
      degrees ; 20 degrees  toe-out = -4.1 degrees ). Toe-in compared to toe-out
      walking also increased rearfoot inversion at initial contact (7.4 degrees  vs 3.1
      degrees  at 10 degrees  toe-out and 1.9 degrees  at 20 degrees  toe-out; P <
      .001) and frontal plane rearfoot angle excursion (9.0 degrees  vs 6.8 degrees  at
      10 degrees  toe-out and 6.0 degrees  at 20 degrees  toe-out; P < .006). Toe-in
      compared to all other conditions increased peak external ankle inversion moments
      (0.04 Nm/kg vs 0.02 Nm/kg at 0 degrees , 0.02 Nm/kg at 10 degrees  toe-out, and
      0.01 Nm/kg at 20 degrees  toe-out; P < .003). CONCLUSIONS: Toe-in and toe-out
      walking require different ankle/rearfoot biomechanics, though no differences in
      discomfort were observed. Longer-term studies are required to properly assess
      these relationships in knee osteoarthritis populations. LEVEL OF EVIDENCE: Level
      IV.

PMID- 30195709
TI  - Transcriptomics analysis reveals candidate genes and pathways for susceptibility
      or resistance to Singapore grouper iridovirus in orange-spotted grouper
      (Epinephelus coioides).
AB  - In this study, the transcriptional response of grouper to Singapore grouper
      iridovirus (SGIV) stimulation was characterized using RNA sequencing.
      Transcriptome sequencing of three test groups in the grouper was performed using
      the Illumina MiSeq platform. The three test groups were a control group, which
      was injected with PBS buffer; a high-susceptible (HS) group, which died shortly
      after the SGIV injection; and a high-resistance (HR) group, which survived the
      SGIV injection. In total, 38,253 unigenes were generated. When the HS group was
      compared with the control group, 885 unigenes were upregulated and 487 unigenes
      were downregulated. When the HR and control groups were compared, 1114 unigenes
      were upregulated and 420 were downregulated, and when the HR and HS groups were
      compared, 1010 unigenes were upregulated and 375 were downregulated. In the KEGG
      analysis, two immune-related pathways, the p53 and peroxisome proliferator
      activated receptor pathways, were detected with highly significant enrichment. In
      addition, 7465 microsatellites and 22,1569 candidate single nucleotide
      polymorphisms were identified from our transcriptome data. The results suggested
      several pathways that are associated with traits of disease susceptibility or
      disease resistance, and provided extensive information about novel gene
      sequences, gene expression profiles, and genetic markers. This may contribute to
      vaccine research and a breeding program against SGIV infection in grouper.

PMID- 30195710
TI  - Analysis of the Atlantic salmon genome reveals a cluster of Mx genes that respond
      more strongly to IFN gamma than to type I IFN.
AB  - Mx proteins are antiviral GTPases, which are induced by type I IFN and virus
      infection. Analysis of the Atlantic salmon genome revealed the presence of 9 Mx
      genes localized to three chromosomes. A cluster of three Mx genes (SsaMx1 -
      SsaMx3), which includes previously cloned Mx genes, is present on chromosome
      (Chr) 12. A cluster of five Mx genes (SsaMx4-SsaMx8) is present on Chr25 while
      one Mx gene (SsaMx9) is present on Chr9. Phylogenetic and gene synteny analyses
      showed that SsaMx1-SsaMx3 are most closely related to the main group of teleost
      Mx proteins. In contrast, SsaMx 4-SsaMx9 formed a separate group together with
      zebrafish MxD and MxG and eel MxB. The Mx cluster in Chr25 showed gene synteny
      similar to a Mx gene cluster in the gar genome. Expression of Mx genes in cell
      lines stimulated with recombinant IFNs showed that Mx genes in Chr12 responded
      more strongly to type I IFN than to type II IFN (IFN gamma) whilst Mx genes in
      Chr25 responded more strongly to IFN gamma than to type I IFNs. SsaMx9 showed no
      response to the IFNs.

PMID- 30195711
TI  - [Subsequent malignancies after long-term follow-up of pediatric hematopoietic
      stem cell transplantation].
AB  - INTRODUCTION: Survival after hematopoietic stem cell transplantation has improved
      dramatically in recent years. Unfortunately, there is an increased risk of
      subsequent malignant neoplasms (SMN) in this population and this represents a
      significant cause of late mortality. PATIENTS AND METHODS: In this study, we
      analyzed the incidence of SMN and the associated risk factors in patients
      referred at a pediatric age for hematopoietic stem cell transplantation
      (allogeneic or autologous) in our center. RESULTS: We observed 19 cases of SMN in
      a cohort of 371 patients, with a cumulative incidence of 6, 12, and 36% at 15,
      20, and 30 years of follow-up, respectively. The solid tumors were the most
      prevalent malignancies. The risk was significantly higher than expected in the
      general population for each tumor type and in the different age ranges (p<.0001).
      Radiotherapy and chronic GvHD were the main risk factors for the development of
      SMN in our series. CONCLUSIONS: We observed a high incidence of SMN among
      hematopoietic stem cell transplantation survivors highlighting the need for life
      long surveillance.

PMID- 30195712
TI  - Role of protein kinase Cdelta in dopaminergic neurotoxic events.
AB  - The pro-apoptotic role of Protein kinase Cdelta (PKCdelta), a member of the novel
      PKC subfamily, has been well-documented in various pathological conditions. In
      the central nervous system, the possible role of PKCdelta has been studied,
      mainly in the condition of dopaminergic loss. It has been suggested that the
      phosphorylation of PKCdelta at tyrosine 311 residue (Tyr311) by redox-sensitive
      Src family kinases (SFKs) is critical for the caspase-3-mediated proteolytic
      cleavage, which produces the constitutively active cleaved form of PKCdelta.
      Mitochondrial translocation of cleaved PKCdelta has been suggested to facilitate
      mitochondria-derived apoptosis and oxidative burdens. Moreover, it has been
      suggested that PKCdelta contribute to neuroinflammation through the
      transformation of microglia into the pro-inflammatory M1 phenotype and the
      assembly of membrane NADPH oxidase in dopaminergic impairments. Interestingly,
      mitochondrial respiratory chain inhibitors or neuroinflammogens have shown to
      induce PKCdelta activation in dopaminergic systems. Thus, PKCdelta activation may
      be one of the pivotal causes of neuropathologic events, and could amplify these
      processes further in a positive feedback manner. Furthermore, PKCdelta may play
      an intermediary role in connecting each neuropathologic event. This review
      affords insight into the role of PKCdelta in various dopaminergic neurotoxic
      models, which could provide a potential target for mitigating dopaminergic
      neurotoxicity.

PMID- 30195714
TI  - Accelerating multi-slice spatiotemporally encoded MRI with simultaneous echo
      refocusing.
AB  - Single-shot spatiotemporally encoded (SPEN) ultrafast magnetic resonance imaging
      (MRI) is of great value to both scientific research and clinical application
      owing to its capability for delivering MR images with greater robustness to
      magnetic field inhomogeneity and chemical-shift displacement effects than
      conventional methods like EPI due to high effective phase-encoded bandwidth. Many
      SPEN MRI methods have been developed, among which multi-slice SPEN MRI arises as
      a promising supplement to ultrafast multi-slice sampling. In this work, we
      propose a new multi-slice SPEN MRI method, termed multi-echo segmented SPEN (ME
      SeSPEN) method, which produces multiple images within a single train of echoes
      and successively samples widely separated slices. The resulting images were
      reconstructed using de-convolution super-resolved algorithm. The robustness and
      efficiency of the proposed method were demonstrated by phantom, lemon and in vivo
      experiments in comparison with spin-echo EPI, spin-echo simultaneous echo
      refocusing (SER), and segmented SPEN (SeSPEN) MRI. The results indicate that the
      new method effectively shortens the sampling time (20% reduction practically in
      comparison with SeSPEN when two slices are simultaneously sampled). ME-SeSPEN
      also reduces eddy current effects while maintaining the benefits of SPEN MRI,
      such as similar robustness to field inhomogeneity, spatial resolution and signal
      to-noise ratio to SeSPEN MRI. The new method will promote the versatility of
      multi-slice MRI in practical applications.

PMID- 30195713
TI  - Nuclear Factor I Represses the Notch Effector HEY1 in Glioblastoma.
AB  - Glioblastomas (GBMs) are highly aggressive brain tumors with a dismal prognosis.
      Nuclear factor I (NFI) is a family of transcription factors that controls glial
      cell differentiation in the developing central nervous system. NFIs have
      previously been shown to regulate the expression of astrocyte markers such as
      glial fibrillary acidic protein (GFAP) in both normal brain and GBM cells. We
      used chromatin immunoprecipitation (ChIP)-on-chip to identify additional NFI
      targets in GBM cells. Analysis of our ChIP data revealed ~400 putative NFI target
      genes including an effector of the Notch signaling pathway, HEY1, implicated in
      the maintenance of neural stem cells. All four NFIs (NFIA, NFIB, NFIC, and NFIX)
      bind to NFI recognition sites located within 1 kb upstream of the HEY1
      transcription site. We further showed that NFI negatively regulates HEY1
      expression, with knockdown of all four NFIs in GBM cells resulting in increased
      HEY1 RNA levels. HEY1 knockdown in GBM cells decreased cell proliferation,
      increased cell migration, and decreased neurosphere formation. Finally, we found
      a general correlation between elevated levels of HEY1 and expression of the brain
      neural stem/progenitor cell marker B-FABP in GBM cell lines. Knockdown of HEY1
      resulted in an increase in the RNA levels of the GFAP astrocyte differentiation
      marker. Overall, our data indicate that HEY1 is negatively regulated by NFI
      family members and is associated with increased proliferation, decreased
      migration, and increased stem cell properties in GBM cells.

PMID- 30195715
TI  - The generalized Stejskal-Tanner equation for non-uniform magnetic field
      gradients.
AB  - The intensity of the diffusion weighted NMR signal is described by the Stejskal
      Tanner equation, which was derived under the assumption that the gradients are
      uniform throughout the sample. Nevertheless, it has been demonstrated numerous
      times that this condition is not fulfilled in the cases of virtually any clinical
      or research MRI scanners. Therefore, technically, the Stejskal-Tanner equation is
      valid only for a very specific case of homogeneous gradients. In this paper the
      Stejskal-Tanner equation was derived for the general case on non-uniform
      diffusion gradients. To this end, the magnetic field was expressed as linear in a
      curvilinear coordinate system defined by a vector function p(r). Thereafter, the
      expression for the non-linear magnetic field was put into the Bloch-Torrey
      equation and solved. Moreover, the meaning of so-called coil tensor, which is
      used for the gradients inhomogeneity correction, was explained. It was proven
      that in the case of the spin echo-based sequences, the Stejskal-Tenner equation
      is still valid, even if the diffusion gradients are non-uniform. However, in such
      a case, the b-matrix should be derived for each voxel separately. For other
      sequence, the derived relation possesses an imaginary term, which corresponds do
      the phase shift of the diffusion weighted signal.

PMID- 30195716
TI  - [Sexual consequences of BPH treatments].
AB  - OBJECTIVE: To review the literature on the sexual adverse effects of
      pharmacological, instrumental and surgical treatments of lower urinary tract
      symptoms related to benign prostatic hyperplasia (LUTS/BPH). METHOD: A non
      systematic review of the scientific literature was conducted from the PubMed
      database to retrieve the most relevant scientific publications. A first research
      was cross-referenced with the results of literature reviews already published and
      enriched by the authors of this review. RESULTS AND CONCLUSION: Sexual
      dysfunction and SBAU/BPH are intimately linked by a cross-over effect in the
      population of men over 50, a possible common pathophysiology and treatments for
      BPH with sexual consequences. Evaluating the sexuality of patients in care for
      SBAU/BPH is therefore essential. Patients should be informed of potential adverse
      drug effects of BPH, including ejaculation disorders with alpha blockers and loss
      of libido and erectile dysfunction with 5 alpha reductase inhibitors. After BPH
      surgery, loss of antegrade ejaculation is common, although preservation
      possibilities exist. The improvement of urinary function and the decrease of
      possible ejaculatory pains have a beneficial effect on the sexuality of the BPH
      patients operated. More rarely, patients may experience orgasmic dysfunction or
      even erectile dysfunction with a possible thermal effect on the vasculo-nerve
      bundles. LEVEL OF EVIDENCE: Consensus d'experts.

PMID- 30195717
TI  - SENS-U: validation of a wearable ultrasonic bladder monitor in children during
      urodynamic studies.
AB  - PURPOSE: Urinary incontinence is a common problem in school-age children. Because
      many children remain unaware of a full-bladder sensation, the SENS-UTM Bladder
      Sensor was developed. The SENS-U is a small, wearable ultrasound sensor, which is
      positioned on the lower abdomen using a skin-friendly adhesive. The sensor
      continuously estimates the bladder filling status and informs the user when it is
      time to go to the toilet. In this study, the clinical performance of the SENS-U
      is evaluated in children during (video) urodynamics. MATERIAL AND METHODS: In
      this study, 30 children (6-12 years) were included who were scheduled for a
      (video) urodynamic study. During urodynamics, the SENS-U determined the average
      anterior-posterior (A-P) bladder dimension (every 30 s) to estimate the filling
      status. The correlation between the average A-P bladder dimension and the infused
      volume is analyzed by Spearman's correlation. RESULTS: Thirty patients
      (boys/girls: 15/15; mean age: 7.9 +/- 1.4 years) were included, in whom the SENS
      U detected the full bladder before voiding in 90% of the patients (27/30). In the
      other patients, the bladder was outside the detection area due to either
      erroneous sensor placement (n = 1) or an (relative) obese abdomen in the upright
      position (n = 2). There was a strong correlation (median rs = 0.94) between the
      average A-P bladder dimension and the infused volume. The detectable maximum
      bladder volume ranged between 71 and 463 ml. CONCLUSION: The SENS-U is able to
      detect a full bladder with a success rate of 90%. When excluding erroneous data
      due to sensor misplacement or an (relative) obese abdomen, the detection rate may
      even be higher. Future research will focus on investigating the effect of theSENS
      U in incontinence training.

PMID- 30195718
TI  - Society of Family Planning clinical recommendations: contraception after surgical
      abortion.
AB  - These recommendations present an evidence-based assessment of provision of
      contraceptives at the time of surgical abortion. Most methods of contraception,
      including the intrauterine devices (IUD), implant, depot medroxyprogesterone
      injection, oral contraceptive pill, contraceptive patch, monthly vaginal ring,
      barrier methods and some permanent methods, can be safely initiated immediately
      after first- or second-trimester surgical abortion. Provision of postabortion
      contraceptives, particularly IUDs and implants, substantially reduces subsequent
      unintended pregnancy. IUD insertion immediately following uterine aspiration is
      safe. While this may be associated with a higher risk of device expulsion than
      with interval placement, expulsion rates remain low, and this risk must be
      weighed against the fact that patients often do not receive their desired IUD at
      an interval insertion and therefore experience higher rates of subsequent
      unintended pregnancy. Many patients experience barriers that prevent access to
      the full spectrum of postabortion contraceptive options, particularly IUDs and
      implants. Advancements in health-systems-based point-of-care provision and
      policies are needed to improve comprehensive contraceptive availability following
      surgical abortion. These recommendations will address clinical considerations for
      postabortion contraceptive provision and recommend interventions to improve
      contraceptive access following uterine evacuation.

PMID- 30195719
TI  - [Accreditation in neurosurgery].

PMID- 30195720
TI  - Cryptococcal meningitis in an immunocompetent patient with obstructive
      hydrocephalus: A case report.
AB  - BACKGROUND: Cryptococcal infections of the central nervous system are very rare
      in immunocompetent patients. They usually present as meningitis or as fungal
      cysts with or without hydrocephalus. Rapid diagnosis and treatment is crucial to
      the prognosis. CASE REPORT: We report the case of an immunocompetent 40-year-old
      male patient with no medical or surgical history and no recent travel, who was
      hospitalized in our neurosurgery department because of a rapidly worsening
      headache. The neurological examination revealed no focal deficit but worrying
      signs of increased intracranial pressure. Magnetic resonance imaging (MRI) with
      contrast showed thick and large-scale cortico-pial cerebellar enhancements,
      associated with severe obstructive hydrocephalus. This required emergency
      endoscopic ventriculocisternostomy during which we observed cottony tissues along
      the ventricular walls. Biopsied tissues and cerebrospinal fluid samples (CSF)
      were not contributive. A CT scan of the chest and abdomen and blood markers of
      common primary tumors were all negative. No evidence of HIV infection or any
      cause of immunosuppression was identified. Symptoms and a second MRI slightly
      improved with intravenous corticosteroid therapy. The hypothesis of a lymphoma or
      granulomatous disease was made initially for which direct surgical biopsies were
      scheduled. The diagnosis of cryptococcal meningitis was obtained later on by
      simultaneous plasma and CSF Cryptococcus antigen detection. Cryptococcus
      neoformans (formerly C. neoformans var. grubii [serotype A]) was then identified
      by PCR. Clinical improvement was obtained with antifungal therapy. CONCLUSION:
      Cryptococcal meningitis is a well-known condition in immunocompromised patients,
      often causing hydrocephalus requiring neurosurgical management. The diagnosis is
      more difficult in patients with no history of HIV or organ transplant.
      Neurologists and neurosurgeons must consider this possibility in case of diffuse,
      thick leptomeningeal enhancement on MRI.

PMID- 30195721
TI  - Hospital surface contamination with antimicrobial-resistant Gram-negative
      organisms in Tanzanian regional and tertiary hospitals: the need to improve
      environmental cleaning.

PMID- 30195722
TI  - Free-breathing coronary CT angiography using 16-cm wide-detector for challenging
      patients: comparison with invasive coronary angiography.
AB  - AIM: To investigate the superiority of free-breathing coronary computed
      tomography angiography (CCTA) with 16-cm wide-detector CT for challenging
      patients who cannot hold their breath. MATEIALS AND METHODS: A total of 76
      patients (62% with either heart rate >75 beats/min or arrhythmia) who were unable
      to breath-hold underwent both free-breathing CCTA and invasive coronary
      angiography (ICA) were included. Two reviewers evaluated coronary arteries on a
      per-segment, per-vessel, and per-patient basis for image quality using a four
      point scale and stenosis degree. CCTA results were compared with ICA to calculate
      the diagnostic accuracy, sensitivity, specificity, positive predictive value
      (PPV), and negative predictive value (NPV). RESULTS: Out of 1,368 segments, 228
      (16.7%) were <1.5 mm in diameter and were excluded. Thirty-two (2.3%) with
      calcification and 26 (1.9%) with motion artefacts were considered positive at CT.
      One thousand and eighty-two segments (79.1%) were evaluated both on CCTA and ICA,
      and 128 (11.8%) segments had >=50% stenosis on ICA. The diagnostic accuracy,
      sensitivity, specificity, PPV, and NPV of CCTA were 90.8%, 88.3%, 91.1%, 57.1%,
      and 98.3% on a per-segment basis; 93.4%, 90.6%, 94.2%, 80.5% and 97.4% on a per
      vessel basis; and 92.1%, 100%, 85%, 85.7% and 100% on a per-patient basis. For
      patients with high heart rates or arrhythmia, 81% (versus 79.1%) segments were
      evaluable, and the accuracy, sensitivity, specificity, PPV, and NPV were
      statistically the same as the entire study population. CONCLUSION: Free-breathing
      CCTA using 16-cm wide-detector CT has high accuracy compared to ICA for detecting
      coronary artery stenosis for challenging patients.

PMID- 30195723
TI  - Ultra-low radiation dose CT angiography of the lower extremity using the
      iterative model reconstruction (IMR) algorithm.
AB  - AIM: To investigate the image quality of lower-extremity computed tomography (CT)
      angiography (CTA) with ultra-low radiation dose using the iterative model
      reconstruction (IMR) algorithm. MATERIALS AND METHODS: Lower-extremity CTA was
      acquired using a 256-multidetector CT system from 90 patients assigned into three
      groups: (1) the routine dose (RD) group: 120 kVp, automatic tube current
      modulation (ACTM) with an image quality index of 12, and filtered back projection
      (FBP); (2) the low-dose (LD) group: 80 kVp, ACTM with an image quality index of
      1, and IMR; and (3) the ultra-low dose (ULD) group: 80 kVp, 20 mAs, and IMR. CT
      attenuation, image noise, signal-to-noise ratio (SNR), and contrast-to-noise
      ratio (CNR) of the lower-extremity arteries were calculated. Subjective image
      quality of lower-extremity segments was assessed. Effective radiation dose was
      recorded. RESULTS: The radiation dose was reduced by 91.4% and 67.3% in the ULD
      group (0.15+/-0.02 mSv) compared to the RD group (1.86+/-0.51 mSv) and the LD
      group (0.49+/-0.08 mSv; both p<0.05). Higher CT attenuation, SNR, CNR, and lower
      image noise were obtained in the ULD group and the LD group compared to the RD
      group (all p<0.05). Better subjective image quality in lower leg segments was
      obtained in the ULD group and the LD group compared to the RD group (all p<0.05).
      No difference was found between the ULD and LD groups in both objective and
      subjective image quality (all p>0.05). CONCLUSION: By using IMR during lower
      extremity CTA, the radiation dose is reduced by up to 91.4% without compromising
      image quality.

PMID- 30195724
TI  - CRISPR-Induced Deletion with SaCas9 Restores Dystrophin Expression in Dystrophic
      Models In Vitro and In Vivo.
AB  - Duchenne muscular dystrophy (DMD), a severe hereditary disease affecting 1 in
      3,500 boys, mainly results from the deletion of exon(s), leading to a reading
      frameshift of the DMD gene that abrogates dystrophin protein synthesis. Pairs of
      sgRNAs for the Cas9 of Staphylococcus aureus were meticulously chosen to restore
      a normal reading frame and also produce a dystrophin protein with normally phased
      spectrin-like repeats (SLRs), which is not usually obtained by skipping or by
      deletion of complete exons. This can, however, be obtained in rare instances
      where the exon and intron borders of the beginning and the end of the complete
      deletion (patient deletion plus CRISPR-induced deletion) are at similar positions
      in the SLR. We used pairs of sgRNAs targeting exons 47 and 58, and a normal
      reading frame was restored in myoblasts derived from muscle biopsies of 4 DMD
      patients with different exon deletions. Restoration of the DMD reading frame and
      restoration of dystrophin expression were also obtained in vivo in the heart of
      the del52hDMD/mdx. Our results provide a proof of principle that SaCas9 could be
      used to edit the human DMD gene and could be considered for further development
      of a therapy for DMD.

PMID- 30195727
TI  - Reply to "Lipocalin-2 contributes to experimental atherosclerosis in a stage
      dependent manner".

PMID- 30195726
TI  - Modeling of nanoparticle transport through the female reproductive tract for the
      treatment of infectious diseases.
AB  - The secreted mucus layer in the vaginal epithelium presents a formidable barrier
      to the transport of active agents for the prevention and treatment of female
      reproductive tract (FRT) infections. Nanoparticle-mediated drug delivery has been
      proposed to help facilitate the transport and release of active agents through
      the cervicovaginal mucus (CVM) and underlying mucosa. However, both nanoparticles
      (NPs) and free active agents face a variety of challenges, often requiring the
      administration of high localized doses to circumvent leakage and poor penetration
      to targeted intravaginal tissue compartments. To address these challenges,
      "stealth" NP modifications have been investigated, due to their favorable mucus
      penetrating properties, resulting in improved intravaginal active agent retention
      and transport. A number of other NP characteristics including size, surface
      modification type, ligand density, and co-modification, as well as the complexity
      of the FRT tissue are involved in obtaining adequate tissue penetration and, if
      needed, cell internalization. Studies that systematically investigate variations
      of these characteristics have yet to be conducted, with the goal to obtain a
      better understanding of what properties most impact prophylactic and therapeutic
      benefit. To complement the progress made with experimental evaluation of active
      agent transport in in vitro and in vivo, mathematical modeling has recently been
      applied to analyze the transport performance of agents and delivery vehicles in
      the FRT. Here, we build upon this work to simulate NP transport through mucus
      gel, epithelial, and stromal compartments, with the goal to provide a platform
      that can systematically evaluate transport based on NP and tissue
      characteristics. Model parameters such as PEG density and NP release (decay) rate
      from mucus gel into the epithelium, are set from previous in vitro and in vivo
      experimental work that assessed the transport of poly(lactic-co-glycolic acid
      (PLGA) NPs. The modeling results show that while unmodified and 2% PEG-modified
      NPs were retained in mucus for ~1-4 h, dependent upon decay constant values, and
      traverse to the epithelium, no NP penetration was observed in the stroma. In
      contrast, NPs modified with 3% PEG, exhibited prolonged retention in each
      compartment, remaining for ~4-6 h. Moreover, a significant concentration of NPs
      is observed in the stroma, indicating a transition in transport behavior. For NPs
      modified with 5, 8, or 25% PEG, steady retention profiles were noted, which
      gradually decline over 24 h. To supplement this modeling study and to develop a
      more representative experimental system that may be useful in future work, we
      report on the feasibility of constructing single and multicellular layered (MCL)
      culture systems to represent the epithelial and stromal tissue of the FRT. We
      anticipate that a combined mathematical/experimental approach may longer term
      enable prediction and customization of patient tissue-specific approaches to
      attain effective NP-mediated drug delivery and release for the treatment of
      infectious disease.

PMID- 30195725
TI  - PDGF Restores the Defective Phenotype of Adipose-Derived Mesenchymal Stromal
      Cells from Diabetic Patients.
AB  - Diabetes is a chronic metabolic disorder that affects 415 million people
      worldwide. This pathology is often associated with long-term complications, such
      as critical limb ischemia (CLI), which increases the risk of limb loss and
      mortality. Mesenchymal stromal cells (MSCs) represent a promising option for the
      treatment of diabetes complications. Although MSCs are widely used in autologous
      cell-based therapy, their effects may be influenced by the constant crosstalk
      between the graft and the host, which could affect the MSC fate potential. In
      this context, we previously reported that MSCs derived from diabetic patients
      with CLI have a defective phenotype that manifests as reduced fibrinolytic
      activity, thereby enhancing the thrombotic risk and compromising patient safety.
      Here, we found that MSCs derived from diabetic patients with CLI not only exhibit
      a prothrombotic profile but also have altered multi-differentiation potential,
      reduced proliferation, and inhibited migration and homing to sites of
      inflammation. We further demonstrated that this aberrant cell phenotype is
      reversed by the platelet-derived growth factor (PDGF) BB, indicating that PDGF
      signaling is a key regulator of MSC functionality. These findings provide an
      attractive approach to improve the therapeutic efficacy of MSCs in autologous
      therapy for diabetic patients.

PMID- 30195728
TI  - Effects of levocarnitine on cardiac function, urinary albumin, hs-CRP, BNP, and
      troponin in patients with coronary heart disease and heart failure.
AB  - OBJECTIVE: To investigate the effects of levocarnitine on cardiac function,
      urinary albumin (ALB), high-sensitivity C-reactive protein (hs-CRP), brain
      natriuretic peptide (BNP), and troponin in patients with coronary heart disease
      (CHD) and heart failure (HF). METHODS: In total, 246 patients with CHD-caused HF
      were selected and randomly divided into Group A and Group B. A fully automatic
      biochemical analyzer was used to measure the levels of ALB, hs-CRP, BNP, and
      troponin in both groups of patients, and the expression levels of LVDD and LVEF
      were detected by cardiac color ultrasonography. Patients in Group B were
      intravenously injected with 3.0 g of levocarnitine, once per day. After 14 days,
      changes in levels of ALB, hs-CRP, BNP, troponin, LVDD, and LVEF in Group A
      patients were detected. RESULTS: The effective cure rates of patients in both
      groups were 65.8% and 81.3%, respectively, and there was a statistically
      significant difference between the two groups (p < 0.05). After administration of
      levocarnitine, all indicators showed decreasing trends, but the LVEF level
      increased. Among them, patients treated with levocarnitine showed the most
      evident decrease in LVEF. Decrease in BNP was the largest (p < 0.05).
      Additionally, there was no statistical difference in incidence rate between the
      two groups (5.8% vs. 2.5%, p = 0.222). CONCLUSION: Levocarnitine can effectively
      improve ALB, hs-CRP, BNP, troponin, and LVDD levels to improve cardiac function
      rating and thus improve cardiac function.

PMID- 30195729
TI  - Role of interleukin 1-beta in the inflammatory response in a fatty acid amide
      hydrolase-knockout mouse model of Alzheimer's disease.
AB  - The search for novel therapies for the treatment of Alzheimer's disease is an
      urgent need, due to the current paucity of available pharmacological tools and
      the recent failures obtained in clinical trials. Among other strategies, the
      modulation of amyloid-triggered neuroinflammation by the endocannabinoid system
      seems of relevance. Previous data indicate that the enhancement of the
      endocannabinoid tone through the inhibition of the enzymes responsible for the
      degradation of their main endogenous ligands may render beneficial effects. Based
      on previously reported data, in which we described a paradoxical effect of the
      genetic deletion of the fatty acid amide hydrolase, we here aimed to expand our
      knowledge on the role of the endocannabinoid system in the context of Alzheimer's
      disease. To that end, we inhibited the production of interleukin-1beta, one of
      the main inflammatory cytokines involved in the neuroinflammation triggered by
      amyloid peptides, in a transgenic mouse model of this disease by using
      minocycline, a drug known to impair the synthesis of this cytokine. Our data
      suggest that interleukin-1beta may be instrumental in order to achieve the
      beneficial effects derived of fatty acid amide hydrolase genetic inactivation.
      This could be appreciated at the molecular (cytokine expression, amyloid
      production, plaque deposition) as well as behavioral levels (memory impairment).
      We here describe a previously unknown link between the endocannabinoid system and
      interleukin-1beta in the context of Alzheimer's disease that open new
      possibilities for the development of novel therapeutics.

PMID- 30195730
TI  - Rifampicin ameliorates lithium-pilocarpine-induced seizures, consequent
      hippocampal damage and memory deficit in rats: Impact on oxidative, inflammatory
      and apoptotic machineries.
AB  - Epilepsy is one of the serious neurological sequelae of bacterial meningitis.
      Rifampicin, the well-known broad spectrum antibiotic, is clinically used for
      chemoprophylaxis of meningitis. Besides its antibiotic effects, rifampicin has
      been proven to be an effective neuroprotective candidate in various experimental
      models of neurological diseases. In addition, rifampicin was found to have
      promising antioxidant, anti-inflammatory and anti-apoptotic effects. Herein, we
      investigated the anticonvulsant effect of rifampicin at experimental meningitis
      dose (20 mg/kg, i.p.) using lithium-pilocarpine model of status epilepticus (SE)
      in rats. Additionally, we studied the effect of rifampicin on seizure induced
      histopathological, neurochemical and behavioral abnormalities. Our study showed
      that rifampicin pretreatment attenuated seizure activity and the resulting
      hippocampal insults marked by hematoxylin and eosin. Markers of oxidative stress,
      neuroinflammation and apoptosis were evaluated, in the hippocampus, 24 h after SE
      induction. We found that rifampicin pretreatment suppressed oxidative stress as
      indicated by normalized malondialdehyde and glutathione levels. Rifampicin
      pretreatment attenuated SE-induced neuroinflammation and decreased the
      hippocampal expression of interleukin-1beta, tumor necrosis factor-alpha, nuclear
      factor kappa-B, and cyclooxygenase-2. Moreover, rifampicin mitigated SE-induced
      neuronal apoptosis as indicated by fewer positive cytochrome c immunostained
      cells and lower caspase-3 activity in the hippocampus. Furthermore, Morris water
      maze testing at 7 days after SE induction showed that rifampicin pretreatment can
      improve cognitive dysfunction. Therefore, rifampicin, currently used in the
      management of meningitis, has a potential additional advantage of ameliorating
      its epileptic sequelae.

PMID- 30195731
TI  - Smiglaside A ameliorates LPS-induced acute lung injury by modulating macrophage
      polarization via AMPK-PPARgamma pathway.
AB  - Macrophages, which have various phenotypes and diverse functions, are becoming
      the target cells in inflammatory diseases. In this study, we evaluated the
      effects of the natural product smiglaside A, a phenylpropanoid glycoside isolated
      from the traditional Chinese medicinal herb Smilax riparia, on macrophage
      polarization and investigated the underlying mechanisms. We found that smiglaside
      A promoted M2 polarization and reduced M1 polarization in LPS-stimulated RAW264.7
      cells and primary mouse peritoneal macrophages. Further mechanistic studies
      showed that the promoting effect of smiglaside A on M2 polarization was
      attenuated by pharmacological inhibition or gene silencing of AMP-activated
      protein kinase (AMPK) or peroxisome proliferator-activated receptor gamma
      (PPARgamma). Moreover, smiglaside A-enhanced PPARgamma activity was prevented by
      the AMPK inhibitor compound C and by an siRNA. These findings indicate that the
      AMPK-PPARgamma pathway is involved in promotion of M2 macrophages by smiglaside
      A. In a mouse model of LPS-induced acute lung injury, smiglaside A significantly
      increased the survival rate of LPS-injected mice and ameliorated the LPS-induced
      inflammatory response and lung damage. In addition, smiglaside A enhanced the
      protein expression levels of phosphorylated AMPK and PPARgamma in the lung and
      promoted alveolar macrophages to the M2 phenotype in this mouse model. Taken
      together, our results indicate that smiglaside A can promote macrophage
      polarization to an anti-inflammatory M2 phenotype via stimulating the AMPK
      PPARgamma signaling pathway. Our study may provide novel approaches and/or
      targets for drug development to treat inflammatory diseases such as acute lung
      injury and sepsis.

PMID- 30195732
TI  - The activity of brain and liver cytochrome P450 2D (CYP2D) is differently
      affected by antidepressants in the chronic mild stress (CMS) model of depression
      in the rat.
AB  - The effect of two second-generation antidepressants escitalopram and venlafaxine
      on the activity of brain and liver cytochrome P450 2D (CYP2D) involved in the
      metabolism of psychotropics and neurotransmitters was determined in the chronic
      mild stress (CMS) model of depression. Escitalopram or venlafaxine (10 mg/kg
      ip/day each) were administered to control and CMS rats for 5 weeks. The activity
      of CYP2D was studied by measurement of the rate of bufuralol 1'-hydroxylation in
      microsomes derived from the liver or different brain structures. The obtained
      results indicate that CMS and the studied antidepressants had different effects
      on the CYP2D activity depending on the location of the enzyme. In the brain, CMS
      produced an increase in the CYP2D activity in the hippocampus. Chronic
      escitalopram or venlafaxine had no effect on the CYP2D activity in the brain of
      nonstressed rats, however, the antidepressants increased the enzyme activity in
      the frontal cortex, hypothalamus and cerebellum of stressed animals. In the
      liver, CMS did not affect the CYP2D activity, while chronic escitalopram or
      venlafaxine significantly decreased the CYP2D activity and protein level in
      nonstressed and stressed rats. We conclude that: 1) CMS stimulates the CYP2D
      activity in the hippocampus and triggers the stimulatory effect of
      antidepressants on CYP2D in other brain structures; 2) the local brain metabolism
      of CYP2D substrates (neurosteroids, neurotransmitters, psychotropics) may be
      enhanced by CMS and/or antidepressants; 3) in contrast to the brain, the liver
      metabolism of CYP2D substrates may be slower during long-term treatment with
      escitalopram or venlafaxine.

PMID- 30195733
TI  - Glucagon-like peptide-1 receptor internalisation controls spatiotemporal
      signalling mediated by biased agonists.
AB  - The glucagon-like peptide-1 receptor (GLP-1R) is a major therapeutic target in
      the treatment of type 2 diabetes due to its roles in regulating blood glucose and
      in promoting weight loss. Like many GPCRs, it is pleiotropically coupled, can be
      activated by multiple ligands and is subject to biased agonism. The GLP-1R
      undergoes agonist mediated receptor internalisation that may be associated with
      spatiotemporal control of signalling and biased agonism, although to date, this
      has not been extensively explored. Here, we investigate GLP-1R trafficking and
      its importance with regard to signalling, including the localisation of key
      signalling molecules, mediated by biased peptide agonists that are either
      endogenous GLP-1R ligands or are used clinically. Each of the agonists promoted
      receptor internalisation through a dynamin and caveolae dependent mechanism and
      traffic the receptor to both degradative and recycling pathways. This
      internalisation is important for signalling, with cAMP and ERK1/2 phoshorylation
      (pERK1/2) generated by both plasma membrane localised and internalised receptors.
      Further assessment of pERK1/2 revealed that all peptides induced nuclear ERK
      activity, but ligands, liraglutide and oxyntomodulin that are biased towards
      pERK1/2 relative to cAMP (when compared to GLP-1 and exendin-4), also stimulated
      pERK1/2 activity in the cytosol. This compartmentalisation of ERK1/2 signalling
      was reliant on receptor internalisation, with restriction of receptor
      localisation to the plasma membrane limiting ERK1/2 signalling to the cytosol.
      Thus, this study implicates a role of receptor internalisation in spatiotemporal
      control of ERK1/2 signalling that may contribute to GLP-1R biased agonism.

PMID- 30195734
TI  - The endocannabinoid 2-arachidonoylglycerol regulates oligodendrocyte progenitor
      cell migration.
AB  - While the endocannabinoid 2-arachidonoylglycerol (2-AG) is thought to enhance the
      proliferation and differentiation of oligodendrocyte progenitor cells (OPCs) in
      vitro, less is known about how endogenous 2-AG may influence the migration of
      these cells. When we assessed this in Agarose drop and Boyden chemotaxis chamber
      assays, inhibiting the sn-1-diacylglycerol lipases alpha and beta (DAGLs) that
      are responsible for 2-AG synthesis significantly reduced the migration of OPCs
      stimulated by platelet-derived growth factor-AA (PDGF) and basic fibroblast
      growth factor (FGF). Likewise, antagonists of the CB1 and CB2 cannabinoid
      receptors (AM281 and AM630, respectively) produced a similar inhibition of OPC
      migration. By contrast, increasing the levels of endogenous 2-AG by blocking its
      degradation (impairing monoacylglycerol lipase activity with JZL-184)
      significantly increased OPC migration, as did agonists of the CB1, CB2 or CB1/CB2
      cannabinoid receptors. This latter effect was abolished by selective CB1 or CB2
      antagonists, strongly suggesting that cannabinoid receptor activation
      specifically potentiates OPC chemotaxis and chemokinesis in response to PDGF/FGF.
      Furthermore, the chemoattractive activity of these cannabinoid receptor agonists
      on OPCs was even evident in the absence of PDGF/FGF. In cultured brain slices
      prepared from the corpus callosum of postnatal rat brains, DAGL or cannabinoid
      receptor inhibition substantially diminished the in situ migration of Sox10+
      OPCs. Overall, these results reveal a novel function of endogenous 2-AG in PDGF
      and FGF induced OPC migration, highlighting the importance of the endocannabinoid
      system in regulating essential steps in oligodendrocyte development.

PMID- 30195735
TI  - PPARalpha/CB1 receptor dual ligands as a novel therapy for alcohol use disorder:
      Evaluation of a novel oleic acid conjugate in preclinical rat models.
AB  - Recent studies have demonstrated the utility of drugs modulating the endogenous
      cannabinoid system to control excessive alcohol intake. Among them, drugs
      interacting with acylethanolamide receptors including cannabinoid CB1 receptor
      antagonists/inverse agonists, peroxisome proliferator-activated receptor alpha
      (PPARalpha) agonists or peroxisome proliferator-activated receptor gamma
      (PPARgamma) agonists have demonstrated utility in the reduction of alcohol intake
      in animal models. However, few studies have addressed the potential utility of
      combining these classes of drugs, especially because of expected safety problems.
      In the present work we took the advantage of the availability of two novel dual
      ligands for these receptors, to test the hypothesis that these types of drugs
      might reproduce and even improve the pharmacological profile of those drugs
      interacting with single targets. To this end we tested (R)-3-[(4-Benzyl-2
      oxooxazolidin-3-yl)methyl]-N-[4-(dodecylcarbamoyl)phenyl]benzamide (NF 10-360), a
      dual PPARalpha/gamma agonist, and N-[1-(3,4-dihydroxyphenyl)propan-2-yl]oleamide
      (OLHHA), a dual CB1 receptor antagonist/PPARalpha agonist, in animal models of
      alcohol consumption. Both drugs were effective in reducing alcohol intake and
      alcohol self-administration, being OLHHA a very potent alcohol intake inhibitor
      (EC50 0.2 mg/kg). OLHHA also reduced self-administration of the opioid oxycodone.
      OLHHA actions on alcohol self-administration were replicated in alcohol
      preferring Marchigian-Sardinian msP rats. Repeated administration of OLHHA did
      result neither in tolerance nor in toxicological or deleterious metabolic changes
      in the liver of msP rats. These data support the feasibility of developing novel
      dual ligands interacting with cannabinoid targets to treat alcohol use disorder
      in humans.

PMID- 30195736
TI  - Targeting Glioma Initiating Cells with A combined therapy of cannabinoids and
      temozolomide.
AB  - Glioblastoma multiforme (GBM) is the most frequent and aggressive type of brain
      tumor due, at least in part, to its poor response to current anticancer
      treatments. These features could be explained, at least partially, by the
      presence within the tumor mass of a small population of cells termed Glioma
      Initiating Cells (GICs) that has been proposed to be responsible for the relapses
      occurring in this disease. Thus, the development of novel therapeutic approaches
      (and specifically those targeting the population of GICs) is urgently needed to
      improve the survival of the patients suffering this devastating disease. Previous
      observations by our group and others have shown that Delta9-Tetrahydrocannabinol
      (THC, the main active ingredient of marijuana) and other cannabinoids including
      cannabidiol (CBD) exert antitumoral actions in several animal models of cancer,
      including gliomas. We also found that the administration of THC (or of THC + CBD
      at a 1:1 ratio) in combination with temozolomide (TMZ), the benchmark agent for
      the treatment of GBM, synergistically reduces the growth of glioma xenografts. In
      this work we investigated the effect of the combination of TMZ and THC:CBD
      mixtures containing different ratios of the two cannabinoids in preclinical
      glioma models, including those derived from GICs. Our findings show that TMZ +
      THC:CBD combinations containing a higher proportion of CDB (but not TMZ + CBD
      alone) produce a similar antitumoral effect as the administration of TMZ together
      with THC and CBD at a 1:1 ratio in xenografts generated with glioma cell lines.
      In addition, we also found that the administration of TMZ + THC:CBD at a 1:1
      ratio reduced the growth of orthotopic xenografts generated with GICs derived
      from GBM patients and enhanced the survival of the animals bearing these
      intracranial xenografts. Remarkably, the antitumoral effect observed in GICs
      derived xenografts was stronger when TMZ was administered together with
      cannabinoid combinations containing a higher proportion of CBD. These findings
      support the notion that the administration of TMZ together with THC:CBD
      combinations - and specifically those containing a higher proportion of CBD - may
      be therapeutically explored to target the population of GICs in GBM.

PMID- 30195737
TI  - Disordered eating behaviors as a potential obesogenic factor in schizophrenia.
AB  - Whilst people with schizophrenia have high levels of obesity and metabolic
      disease, our understanding of their eating behaviors is still limited. Our aim
      was to evaluate the relationships between eating behavior and clinical data in
      schizophrenia. A cross-sectional study including 66 schizophrenia outpatients
      compared to 81 healthy controls was undertaken. Eating behavior was assessed
      using the shortened 21-item version of the Three-Factor Eating Questionnaire
      (TFEQ-R21). The patients had a mean of 44 +/- 11 years; a mean BMI of 30.3 +/- 8
      kg/m2 (vs. 24 +/- 3.3 kg/m2 for controls) and a mean duration of illness of 7.2
      +/- 6 years. All mean TFEQ scores were significantly higher in patients
      (indicating poorer eating behaviors) compared to controls after adjustment for
      age and sex, BMI and smoking status. Among patients, mean TFEQ scores were not
      significantly different between men and women samples. The "cognitive restraint"
      factor was significantly higher in schizophrenia patients with a BMI < 25 than in
      the group of overweight patients with a BMI > 25. Our findings suggest that
      disordered eating behaviors affect schizophrenia patients regardless of gender or
      duration of disease compared to controls. More research is needed to help clarify
      the relationships between eating behaviors and weight-related outcomes in
      schizophrenia.

PMID- 30195738
TI  - Prediction of psychotherapy process and outcome with the Personality Assessment
      Inventory.
AB  - The Personality Assessment Inventory (PAI; Morey, 1991) contains scales that were
      designed to make predictions about how an individual might respond to treatment,
      thereby allowing clinicians to attune treatment plans to a client's specific
      needs. The present study utilized two features of the PAI as predictors of
      treatment process and outcome in a sample of 47 outpatient veterans: the
      Treatment Rejection (RXR) scale and the Treatment Process Index (TPI). Data were
      collected for three treatment process and outcome measures: treatment utilization
      (ratio of appointments attended to appointments scheduled), therapist-rated
      therapeutic alliance, and symptom change over time. Results indicated that RXR
      significantly predicted utilization over and above the TPI. The TPI significantly
      predicted the rate of distress symptom decline over time, but RXR did not.
      Lastly, neither RXR nor the TPI were significant predictors of therapist-rated
      alliance.

PMID- 30195739
TI  - A lab-based study exploring the associations among nonsuicidal self-injury, pain,
      and emotion among university students.
AB  - Nonsuicidal self-injury (NSSI; e.g., self-cutting without lethal intent) is a
      widespread mental health concern among emerging adults in university. Although
      accumulating evidence suggests that NSSI is primarily an emotion coping
      behaviour, little is known about variability in emotional response to pain among
      individuals who self-injure. Recent theory on NSSI suggests that individuals who
      engage in NSSI to self-punish may experience additional affective gains in
      response to pain compared to individuals without self-punishment motivations for
      NSSI and individuals who do not self-injure. To test this hypothesis, 82
      undergraduate students (Mage = 21.52 years) were recruited from a mid-sized
      university, and reported on their emotions three times: at baseline, following a
      stress-induction task, and after a cold-pressor task. Although all participants
      showed decreased negative emotions (e.g., hostility, fear) and increased serenity
      following cold pain, students who engaged in NSSI specifically to self-punish
      also showed decreased guilt and sadness. The present findings demonstrate that
      pain may serve to regulate different emotions for students who self-injure
      depending on their motivations for engaging in NSSI. Additionally, findings
      suggest that prevention and intervention efforts aimed at reducing the need to
      self-punish may help to reduce some of the emotionally reinforcing properties of
      NSSI.

PMID- 30195740
TI  - Decreased levels of serum retinoic acid in chinese children with autism spectrum
      disorder.
AB  - Previous studies framed a possible link of retinoic acid (RA) regulation in brain
      to autism spectrum disorders (ASD) etiology. The aim of this study was to measure
      serum levels of RA in relation to the degree of the severity of autism. Serum RA
      levels were measured by enzyme-linked immunosorbent assay (ELISA) colorimetric
      detection Kit in 81 children with autism and 81 age-sex matched typical
      development children. The severity of autistic symptomatology was measured by the
      Childhood Autism Rating Scale (CARS) score using the Chinese version. The serum
      levels of RA in the children with ASD (1.68 +/- 0.52 ng/ml) were significantly
      lower than those of control subjects (2.13 +/- 0.71 ng/ml) (P < 0.001). At
      admission, 57 children (70.4%) had a severe autism. In those children, the mean
      serum RA levels were lower than in those children with mild to moderate autism
      (1.57 +/- 0.47 ng/ml VS. 1.95 +/- 0.55 ng/ml; P = 0.003). Furthermore, in
      multivariate model, low RA level was associated with having/the presence of ASD
      (adjusted odd ratio[OR] 0.516; P = 0.003) and severe ASD (OR 0.415; P = 0.015)
      after adjusted for confounding factors. The data suggested that serum RA levels
      were reduced in the group with ASD, and the levels negative correlated
      significantly with the severity of autism.

PMID- 30195741
TI  - Identifying Chinese adolescents with a high suicide attempt risk.
AB  - Adolescent suicide has become a serious public health problem in China. Since
      suicide attempts are considered the strongest predictor of suicide completion, it
      is valuable to identify adolescents with a high suicide attempt risk. This study
      aimed to develop a decision tree model for the interactive prediction of high
      suicide attempt risk in Chinese adolescents. A classification tree analysis was
      conducted in a sample of senior high school students (N = 6,686) based on the
      CRUISE program. The results indicated that depression, anxiety, social support,
      gender, self-esteem, family cohesion and adaptability were significant predictors
      of high suicide attempt risk, and interactions among these predictors constructed
      a hierarchical decision tree model. The tree model offered a series of reliable
      rules to identify Chinese adolescents with high suicide attempt risk, for
      example, adolescents with high depression scores had the highest probability
      (69.22%) of having a suicide attempt, female adolescents with low social support
      and low depression scores had the second highest probability (57.58%), and
      adolescents with low anxiety, low family adaptability, and medium depression
      scores had the third highest probability (55.77%). These exploratory findings
      suggested that different screening criteria are needed to detect at-risk Chinese
      adolescents with different severities of depression.

PMID- 30195742
TI  - Evaluation of a few discrete clinical markers may predict categorization of
      actively symptomatic non-acute schizophrenia patients as treatment resistant or
      responders: A study by ROC curve analysis and multivariate analyses.
AB  - Here, we used Receiver Operating Characteristic (ROC) curve analysis to determine
      whether clinical factors may aid predicting the categorization of schizophrenia
      patients as Treatment Resistant (TRS) or antipsychotic responsive schizophrenia
      (ARS). Patients with an established condition of TRS or ARS were assessed for:
      clinical presentation and course; neurological soft signs (NES); psychopathology
      by PANSS; cognitive performances; quality of life scale (QLS); functional
      capacity; social functioning (PSP and SLOF scales). In ROC curve analysis,
      significance indicated that the Area under curve (AUC) allowed distinguishing
      between TRS and ARS. Multivariate analyses were additionally used to provide
      independent predictive analysis. Multiple clinical variables showed significant
      AUCs. The largest significant AUCs were found for: NES total score; SLOF Area2;
      QLS subscale; antipsychotic doses. The highest sensitivity was found for NES
      total score, the highest specificity for previous hospitalizations. The highest
      Odds Ratio of being included within the TRS category were found for: NES total
      score (7.5); QLS total score (5.49); and previous hospitalizations (4.76). This
      same circumscribed group of variables was also found to be predictive of TRS when
      adopting stepwise logistic regression or discriminant analysis. We concluded that
      the evaluation of few clinical factors may provide reliable and accurate
      predictions on whether one schizophrenia patient may be categorized as a TRS.

PMID- 30195743
TI  - Relationship of internet addiction severity with probable ADHD and difficulties
      in emotion regulation among young adults.
AB  - The aim of the present study was to evaluate relationship of Internet addiction
      (IA) symptom severity with probable attention deficit/hyperactivity disorder
      (ADHD) and difficulties in emotion regulation, while controlling the effects of
      depression, anxiety and neuroticism. The study was conducted with online survey
      among 1010 volunteered participants of university students and/or amateur or
      professional gamers. Scale scores were higher among the group with high
      probability of ADHD (n = 190, 18.8%). In linear regression analysis, both
      Inattentiveness and hyperactivity/impulsivity dimensions of ADHD were related
      with the severity of IA symptoms, together with depression and non-accept
      dimension of the Difficulties in Emotion Regulation Scale (DERS). Similarly,
      presence of probable ADHD was related with the severity of IA symptoms in ANCOVA,
      together with depression, neuroticism and non-accept dimension of DERS.
      Participants were two different groups of non-clinical samples and all scales
      were self-rated. Also common comorbidities were not screened. Finally, since this
      study is cross-sectional the findings of this study cannot address the causal
      relationships among the primary constructs of interest. These findings suggest
      that the presence of probable ADHD is related with the severity of IA symptoms,
      together with the difficulties in emotion regulation, particularly non-accept
      dimension, depression and neuroticism among young adults.

PMID- 30195744
TI  - Sleep disturbances, functioning, and quality of life in euthymic patients with
      bipolar disorder.
AB  - There is scarce knowledge about the impact of sleep disturbances on functioning
      and quality of life (QoL). This study aims to investigate the links between sleep
      satisfaction and duration, and functioning and QoL in euthymic BD patients. We
      made a secondary analysis of a cross-sectional, naturalistic, multicenter study.
      Inclusion criteria: DSM-IV BD diagnosis; age > 17 years; written informed
      consent. Sample: 119 Spanish euthymic BD outpatients. Hierarchical multiple
      regressions were performed controlling for confounding factors. We found that
      almost half of the patients reported at least one sleep complaint, nighttime
      awakenings (60.5%) and difficulty falling asleep (31.9%) were the most frequent.
      Long sleep duration was associated with worse global functioning, and also with
      worse occupational functioning along with caffeine consumption. Sleep
      satisfaction was negatively associated with worse QoL in the mental health
      subscale and the summary mental. In both cases, the use of benzodiazepines
      negatively affects these QoL domains. In conclusion, euthymic bipolar patients
      frequently present sleep disturbances that seem to contribute to the impairment
      of their functioning and QoL. Also, the use of benzodiazepines negatively affects
      the QoL of these patients. Thus, a detailed sleep evaluation should be performed,
      and the use of benzodiazepines should be reduced to the minimum.

PMID- 30195745
TI  - Moral injury, suicide ideation, and behavior among combat veterans: The mediating
      roles of entrapment and depression.
AB  - Combat veterans have been identified as a major at-risk group for suicide. Moral
      injury (MI) experiences have recently been acknowledged as significant stressful
      combat events that may lead to psychopathology, such as suicidal ideation and
      behaviors (SIB). In this study, we aimed to examine to what extent potential MI
      events may comprise risk factors for SIB and to explore the mediating role of the
      entrapment experience in this relationship. A sample of 191 Israeli combat
      veterans (Mage = 25.39, SD = 2.37) completed validated self-report questionnaires
      in a cross-sectional design study. All potential MI experiences were
      significantly related to SIB levels among veterans. Moreover, self- and betrayal
      based MI experiences were significantly associated with sense of entrapment,
      which subsequently was associated with high levels of SIB. The integrative model
      indicated that entrapment and depression served as mediators in the association
      of MI-SIB. Even years after their release from military service, veterans exposed
      to potential MI experiences may still feel consumed by their painful memories and
      still have premonitions of a foreshortened future. Thus, they are more prone to
      SIB as well as to other mental health problems.

PMID- 30195747
TI  - The intensity of suicidal ideation at the worst point and its association with
      suicide attempts.
AB  - This study seeks to determine if the severity of suicidal ideation at the worst
      point can differentiate individuals who think about suicide (ideators) from those
      who make a suicide attempt (attempters). Subsequently, the indirect effect of
      worst point ideation on differentiating ideators from attempters through various
      pathways such as an increased capability for suicide, painful and provocative
      experiences, non-suicidal self-injury (NSSI), and planning for suicide was
      examined. The sample included 229 adults with a lifetime history of suicidal
      ideation who were recruited through Amazon's Mechanical Turk program and asked to
      complete a battery of self-report questionnaires. Furthermore, the sample was
      oversampled on the basis of prior suicide attempts. Our results suggest that
      there is a strong relationship between worst point ideation and suicide attempts
      such that there is a greater likelihood of endorsing past suicide attempts when
      individuals reported high intensity at the worst point of their suicidal
      ideation. An elevated level of painful and provocative events partially accounted
      for the aforementioned relationship while a heightened capability for suicide.
      The results from the present study suggest utility in managing intensity of
      suicidal ideation and the importance of addressing painful and provocative
      behaviors to prevent potentially lethal suicide attempts in the future.

PMID- 30195746
TI  - Increased circulating regulatory T cells in medicated people with schizophrenia.
AB  - Immunological abnormalities are increasingly reported in people with
      schizophrenia, but no clear functional biomarkers associated with genetic
      correlates of the disease have been found. Regulatory T cells (Tregs) are key
      immunoregulatory cells involved in the control of inflammatory processes and
      their functions are directly related to the human leucocyte antigen (HLA) gene,
      which has been implicated in schizophrenia genetic studies. However, there is a
      lack of studies reporting Treg status in people with schizophrenia. In the
      current study, the proportion of circulating Tregs was examined using flow
      cytometry in 26 medicated participants with schizophrenia and 17 healthy
      controls. Psychiatric symptoms and cognitive function were evaluated using the
      Scale for the Assessment of Negative Symptoms, the Brief Psychiatric Rating
      Scale, and the MATRICS Consensus Cognitive Battery. The proportion of Tregs was
      found to be significantly greater in the schizophrenia group compared to healthy
      controls. No differences were observed in total lymphocyte counts or CD3+ and
      CD4+ T cells, confirming a specific effect for Tregs. Elevated Tregs in
      schizophrenia correlated with fewer negative symptoms, a core domain of the
      illness. These results suggest that Tregs may contribute to improved negative
      symptoms in schizophrenia, possibly by counteracting on-going inflammatory
      processes.

PMID- 30195748
TI  - The anxiolytic-like effects of estazolam on a PTSD animal model.
AB  - Post-traumatic stress disorder (PTSD) is a serious psychiatric disorder.
      Estazolam has been shown to produce anxiolytic-, hypnotic-, amnestic-, and
      sedative-like effects. However, few studies are concerned about its anti-PTSD
      like effects. The anti-PTSD-like effects of estazolam were evaluated by single
      prolonged stress animal model. After exposure to single prolonged stress, rats
      (Sprague-Dawley, male, 8 weeks) were administered by estazolam (0.5, 1 and 2
      mg/kg, i.p.) from day 2 to 13 once daily. The behavioral assessments were
      performed during treatment with drugs. After the behavioral evaluation, the role
      of allopregnanolone in the anti-PTSD-like effects of estazolam was also evaluated
      via astrocyte cells and brain tissues (e.g. prefrontal cortex, hippocampus, and
      amygdala). The PTSD-like behavioral deficits were significantly blocked by
      estazolam (1 and 2 mg/kg, i.p.) without affecting locomotor activity.
      Consistently, the levels on allopregnanolone were increased by estazolam (1 and 2
      mg/kg, i.p.) in prefrontal cortex, hippocampus, and amygdala. The levels of
      allopregnanolone were increased by sertraline (1 umoL/L) and estazolam (4
      umoL/L), while the effects were antagonized by trilostane (1 umoL/L) and
      finasteride (1 umoL/L) in astrocyte cells, respectively. Collectively, the
      anxiety-like behavior deficits were ameliorated by estazolam in the single
      prolonged stress animal model that was associated with biosynthesis of
      allopregnanolone.

PMID- 30195749
TI  - Sp1 Suppresses miR-3178 to Promote the Metastasis Invasion Cascade via
      Upregulation of TRIOBP.
AB  - Specificity protein (Sp1) plays an important role in invasion-metastasis cascade.
      Sp1 regulation on protein coding genes has been extensively investigated;
      however, little is known about its regulation on protein non-coding genes. In
      this study, miR-3178 is reported as a novel target of Sp1 in multiple cancer cell
      models. Sp1 functions as its transcriptional suppressor as evidenced by
      luciferase reporter and chromatin immunoprecipitation (ChIP) assays. In line with
      the pro-metastatic role of Sp1, miR-3178 exerts anti-metastasis function.
      Overexpression of miR-3178 inhibits both migration and invasion of highly
      metastatic prostate, lung, and breast cancer cells whereas antagonizing miR-3178
      promotes those events in their lowly metastatic counterparts. The in vivo study
      demonstrates that miR-3178 suppresses the tail vein inoculated prostate cancer
      cells to form colonies in lung, lymph node, and liver of BALB/c nude mice. miR
      3178 directly targets the 3' UTR of TRIOBP-1 and TRIOBP-5, two isoforms of TRIOBP
      expressed in prostate, lung, and breast cancer cells. Overexpression of TRIOBP-1
      could rescue miR-3178 inhibition on cell migration and invasion. Collectively,
      our findings reveal the regulatory axis of Sp1/miR-3178/TRIOBP in metastasis
      cascade. Our results suggest miR-3178 as a promising application to suppress
      metastasis in Sp1-overexpressed cancers.

PMID- 30195750
TI  - Targeting the IGF1R Pathway in Breast Cancer Using Antisense lncRNA-Mediated
      Promoter cis Competition.
AB  - Aberrant insulin-like growth factor I receptor (IGF1R) signaling pathway serves
      as a well-established target for cancer drug therapy. The intragenic antisense
      long noncoding RNA (lncRNA) IRAIN, a putative tumor suppressor, is downregulated
      in breast cancer cells, while IGF1R is overexpressed, leading to an abnormal
      IGF1R/IRAIN ratio that promotes tumor growth. To precisely target this pathway,
      we developed an "antisense lncRNA-mediated intragenic cis competition" (ALIC)
      approach to therapeutically correct the elevated IGF1R/IRAIN bias in breast
      cancer cells. We used CRISPR-Cas9 gene editing to target the weak promoter of
      IRAIN antisense lncRNA and showed that in targeted clones, intragenic activation
      of the antisense lncRNA potently competed in cis with the promoter of the IGF1R
      sense mRNA. Notably, the normalization of IGF1R/IRAIN transcription inhibited the
      IGF1R signaling pathway in breast cancer cells, decreasing cell proliferation,
      tumor sphere formation, migration, and invasion. Using "nuclear RNA reverse
      transcription-associated trap" sequencing, we uncovered an IRAIN lncRNA-specific
      interactome containing gene targets involved in cell metastasis, signaling
      pathways, and cell immortalization. These data suggest that aberrantly
      upregulated IGF1R in breast cancer cells can be precisely targeted by cis
      transcription competition, thus providing a useful strategy to target disease
      genes in the development of novel precision medicine therapies.

PMID- 30195751
TI  - Self-Amplifying Replicon RNA Delivery to Dendritic Cells by Cationic Lipids.
AB  - Advances in RNA technology during the past two decades have led to the
      construction of replication-competent RNA, termed replicons, RepRNA, or self
      amplifying mRNA, with high potential for vaccine applications. Cytosolic delivery
      is essential for their translation and self-replication, without infectious
      progeny generation, providing high levels of antigen expression for inducing
      humoral and cellular immunity. Synthetic nanoparticle-based delivery vehicles can
      both protect the RNA molecules and facilitate targeting of dendritic cells
      critical for immune defense development. Several cationic lipids were assessed,
      with RepRNA generated from classical swine fever virus encoding nucleoprotein
      genes of influenza A virus. The non-cytopathogenic nature of the RNA allowed
      targeting to dendritic cells without destroying the cells-important for prolonged
      antigen production and presentation. Certain lipids were more effective at
      delivery and at promoting translation of RepRNA than others. Selection of
      particular lipids provided delivery to dendritic cells that resulted in
      translation, demonstrating that delivery efficiency could not guarantee
      translation. The observed translation in vitro was reproduced in vivo by inducing
      immune responses against the encoded influenza virus antigens. Cationic lipid
      mediated delivery shows potential for promoting RepRNA vaccine delivery to
      dendritic cells, particularly when combined with additional delivery elements.

PMID- 30195752
TI  - Stable Transcriptional Repression and Parasitism of HIV-1.
AB  - Gene-based therapies represent a promising treatment for HIV-1 infection, as they
      offer the potential for sustained viral inhibition and reduced treatment
      interventions. One approach developed here involves using conditionally
      replicating vectors (CR-vectors). CR-vectors utilize HIV-expressed proteins to
      replicate and disseminate along with HIV into the budding viral particles,
      thereby co-infecting target cellular reservoirs. We generated and characterized
      several CR-vectors carrying various therapeutic payloads of non-coding RNAs
      targeted to HIV-1, both transcriptionally and post-transcriptionally. Both virus
      and vector expression was followed in cell culture systems and T cells in the
      presence and absence of mycophenolic acid (MPA) selection. We find here that CR
      vectors functionally suppress HIV expression in a long-term stable manner and
      that transcriptional targeting of and epigenetic silencing of HIV can be passaged
      to newly infected cells by the action of the CR-vector, ultimately establishing a
      sustained parasitism of HIV. Our findings suggest that CR-vectors with modulatory
      non-coding RNAs may be a viable approach to achieving long-term sustained
      suppression of HIV-1, leading ultimately to a functional cure.

PMID- 30195753
TI  - RNA Polymerase II Activity of Type 3 Pol III Promoters.
AB  - In eukaryotes, three RNA polymerases (Pol I, II, and III) are responsible for the
      transcription of distinct subsets of genes. Gene-external type 3 Pol III
      promoters use defined transcription start and termination sites, and they are,
      therefore, widely used for small RNA expression, including short hairpin RNAs in
      RNAi applications and guide RNAs in CRISPR-Cas systems. We report that all three
      commonly used human Pol III promoters (7SK, U6, and H1) mediate luciferase
      reporter gene expression, which indicates Pol II activity, but to a different
      extent (H1 ? U6 > 7SK). We demonstrate that these promoters can recruit Pol II
      for transcribing extended messenger transcripts. Intriguingly, selective
      inhibition of Pol II stimulates the Pol III activity and vice versa, suggesting
      that two polymerase complexes compete for promoter usage. Pol II initiates
      transcription at the regular Pol III start site on the 7SK and U6 promoters, but
      Pol II transcription on the most active H1 promoter starts 8 nt upstream of the
      Pol III start site. This study provides functional evidence for the close
      relationship of Pol II and Pol III transcription. These mechanistic insights are
      important for optimal use of Pol III promoters, and they offer additional
      flexibility for biotechnology applications of these genetic elements.

PMID- 30195754
TI  - Circulating miRNAs as Predictive Biomarkers of Type 2 Diabetes Mellitus
      Development in Coronary Heart Disease Patients from the CORDIOPREV Study.
AB  - Circulating microRNAs (miRNAs) have been proposed as type 2 diabetes biomarkers,
      and they may be a more sensitive way to predict development of the disease than
      the currently used tools. Our aim was to identify whether circulating miRNAs,
      added to clinical and biochemical markers, yielded better potential for
      predicting type 2 diabetes. The study included 462 non-diabetic patients at
      baseline in the CORDIOPREV study. After a median follow-up of 60 months, 107 of
      them developed type 2 diabetes. Plasma levels of 24 miRNAs were measured at
      baseline by qRT-PCR, and other strong biomarkers to predict diabetes were
      determined. The ROC analysis identified 9 miRNAs, which, added to HbA1c, have a
      greater predictive value in early diagnosis of type 2 diabetes (AUC = 0.8342)
      than HbA1c alone (AUC = 0.6950). The miRNA and HbA1c-based model did not improve
      when the FINDRISC was included (AUC = 0.8293). Cox regression analyses showed
      that patients with low miR-103, miR-28-3p, miR-29a, and miR-9 and high miR-30a-5p
      and miR-150 circulating levels have a higher risk of disease (HR = 11.27; 95% CI
      = 2.61-48.65). Our results suggest that circulating miRNAs could potentially be
      used as a new tool for predicting the development of type 2 diabetes in clinical
      practice.

PMID- 30195755
TI  - Parallel Genome-wide Profiling of Coding and Non-coding RNAs to Identify Novel
      Regulatory Elements in Embryonic and Maturated Heart.
AB  - Heart development is a complex process, tightly regulated by numerous molecular
      mechanisms. Key components of the regulatory network underlying heart development
      are transcription factors (TFs) and microRNAs (miRNAs), yet limited investigation
      of the role of miRNAs in heart development has taken place. Here, we report the
      first parallel genome-wide profiling of polyadenylated RNAs and miRNAs in a
      developing murine heart. These data enable us to identify dynamic activation or
      repression of numerous biological processes and signaling pathways. More than 200
      miRNAs and 25 long non-coding RNAs were differentially expressed during embryonic
      heart development compared to the mature heart; most of these had not been
      previously associated with cardiogenesis. Integrative analysis of expression data
      and potential regulatory interactions suggested 28 miRNAs as novel regulators of
      embryonic heart development, representing a considerable expansion of the current
      repertoire of known cardiac miRNAs. To facilitate follow-up investigations, we
      constructed HeartMiR (http://heartmir.sysbiolab.eu), an open access database and
      interactive visualization tool for the study of gene regulation by miRNAs during
      heart development.

PMID- 30195756
TI  - uc.454 Inhibited Growth by Targeting Heat Shock Protein Family A Member 12B in
      Non-Small-Cell Lung Cancer.
AB  - Transcribed ultraconserved regions (T-UCRs) classified as long non-coding RNAs
      (Lnc-RNAs) are transcripts longer than 200-nt RNA with no protein-coding
      capacity. Previous studies showed that T-UCRs serve as novel oncogenes, or tumor
      suppressors are involved in tumorigenesis and cancer progressive. Nevertheless,
      the clinicopathologic significance and regulatory mechanism of T-UCRs in lung
      cancer (LC) remain largely unknown. We found that uc.454 was downregulated in
      both non-small-cell LC (NSCLC) tissues and LC cell lines, and the downregulated
      uc.454 is associated with tumor size and tumors with more advanced stages.
      Transfection with uc.454 markedly induced apoptosis and inhibited cell
      proliferation in SPC-A-1 and NCI-H2170 LC cell lines. Above results suggested
      that uc.454 played a suppressive role in LC. Heat shock protein family A member
      12B (HSPA12B) protein was negatively regulated by uc.454 at the
      posttranscriptional level by dual-luciferase reporter assay and affected the
      expressions of Bcl-2 family members, which finally induced LC apoptosis. The
      uc.454/HSPA12B axis furthers our understanding of the molecular mechanisms
      involved in tumor apoptosis, which may potentially serve as a therapeutic target
      for lung carcinoma.

PMID- 30195757
TI  - Differential Co-expression and Regulatory Network Analysis Uncover the Relapse
      Factor and Mechanism of T Cell Acute Leukemia.
AB  - The pediatric T cell acute lymphoblastic leukemia (T-ALL) still remains a cancer
      with worst prognosis for high recurrence. Massive studies were conducted for the
      leukemia relapse based on diagnosis and relapse paired samples. However, the
      initially diagnostic samples may contain the relapse information and mechanism,
      which were rarely studied. In this study, we collected mRNA and microRNA (miRNA)
      data from initially diagnosed pediatric T-ALL samples with their relapse or
      remission status after treatment. Integrated differential co-expression and miRNA
      transcription factor (TF)-gene regulatory network analyses were used to reveal
      the possible relapse mechanisms for pediatric T-ALL. We detected miR-1246/1248
      and NOTCH2 served as key nodes in the relapse network, and they combined with TF
      WT1/SOX4/REL to form regulatory modules that influence the progress of T-ALL. A
      regulatory loop miR-429-MYCN-MFHAS1 was found potentially associated with the
      remission of T-ALL. Furthermore, we proved miR-1246/1248 combined with NOTCH2
      could promote cell proliferation in the T-ALL cell line by experiments.
      Meanwhile, analysis based on the miRNA-drug relationships demonstrated that drugs
      5-fluorouracil, ascorbate, and trastuzumab targeting miR-1246 could serve as
      potential supplements for the standard therapy. In conclusion, our findings
      revealed the potential molecular mechanisms of T-ALL relapse by the combination
      of co-expression and regulatory network, and they provide preliminary clues for
      precise treatment of T-ALL patients.

PMID- 30195759
TI  - Downregulated lncRNA HOXA11-AS Affects Trophoblast Cell Proliferation and
      Migration by Regulating RND3 and HOXA7 Expression in PE.
AB  - The long noncoding RNA HOXA11-AS displays abnormal expression in numerous human
      diseases. However, its function and biological mechanisms remain unclear in
      preeclampsia (PE). In this study, we report that HOXA11-AS is significantly
      downregulated in preeclamptic placental tissues and could contribute to the
      occurrence and development of PE. Silencing of HOXA11-AS expression could
      significantly suppress trophoblast cell growth and migration, whereas HOXA11-AS
      overexpression facilitated cell growth in the HTR-8/SVneo, JEG3, and JAR cell
      lines. RNA-seq analysis also indicated that HOXA11-AS silencing preferentially
      regulated numerous genes associated with cell proliferation and cell migration.
      Mechanistic analyses showed that HOXA11-AS could recruit Ezh2 and Lsd1 protein
      and regulate RND3 mRNA expression in the nucleus. In the cytoplasm, HOXA11-AS
      modulates HOXA7 expression by sponged miR-15b-5p, affecting trophoblast cell
      proliferation. Together, these data confirm that aberrant expression of HOXA11-AS
      is involved in the occurrence and development of PE and may act as a prospective
      diagnosis and therapeutic target in PE.

PMID- 30195758
TI  - Increased Frataxin Expression Induced in Friedreich Ataxia Cells by Platinum TALE
      VP64s or Platinum TALE-SunTag.
AB  - Frataxin gene (FXN) expression is reduced in Friedreich's ataxia patients due to
      an increase in the number of GAA trinucleotides in intron 1. The frataxin
      protein, encoded by that gene, plays an important role in mitochondria's iron
      metabolism. Platinum TALE (plTALE) proteins targeting the regulatory region of
      the FXN gene, fused with a transcriptional activator (TA) such as VP64 or P300,
      were used to increase the expression of that gene. Many effectors, plTALEVP64,
      plTALEp300, and plTALESunTag, targeting 14 sequences of the FXN gene promoter or
      intron 1 were produced. This permitted selection of 3 plTALEVP64s and 2
      plTALESunTag that increased FXN gene expression by up to 19-fold in different
      Friedreich ataxia (FRDA) primary fibroblasts. Adeno-associated viruses were used
      to deliver the best effectors to the YG8R mouse model to validate their
      efficiencies in vivo. Our results showed that these selected plTALEVP64s or
      plTALESunTag induced transcriptional activity of the endogenous FXN gene as well
      as expression of the frataxin protein in YG8R mouse heart by 10-fold and in
      skeletal muscles by up to 35-fold. The aconitase activity was positively
      modulated by the frataxin level in mitochondria, and it was, thus, increased in
      vitro and in vivo by the increased frataxin expression.

PMID- 30195760
TI  - Spherical Nucleic Acid Architecture Can Improve the Efficacy of Polycation
      Mediated siRNA Delivery.
AB  - Clinical translation of small interfering RNA (siRNA) nanocarriers is hindered by
      limited knowledge regarding the parameters that regulate interactions between
      nanocarriers and biological systems. To address this, we investigated the
      influence of polycation-based nanocarrier architecture on intracellular siRNA
      delivery. We compared the cellular interactions of two polycation-based siRNA
      carriers that have similar size and surface charge but different siRNA
      orientation: (1) polyethylenimine-coated spherical nucleic acids (PEI-SNAs), in
      which polyethylenimine is wrapped around a spherical nucleic acid core containing
      radially oriented siRNA and (2) randomly assembled polyethylenimine-siRNA
      polyplexes that lack controlled architecture. We found that PEI-SNAs undergo
      enhanced and more rapid cellular uptake than polyplexes, suggesting a prominent
      role for architecture in cellular uptake. Confocal microscopy studies
      demonstrated that while PEI-SNAs and polyplexes exhibit similar intracellular
      stability, PEI-SNAs undergo decreased accumulation within lysosomes, identifying
      another advantage conferred by their architecture. Indeed, these advantageous
      cellular interactions enhanced the gene silencing potency of PEI-SNAs by 10-fold
      relative to polyplexes. Finally, cytocompatibility studies showed that PEI-SNAs
      exhibit decreased toxicity per PEI content relative to polyplexes, allowing the
      use of more polycation. Our studies provide critical insight into design
      considerations for engineering siRNA carriers and warrant future investigation of
      how nanocarrier architecture influences cellular-, organ-, and organism-level
      interactions.

PMID- 30195761
TI  - CRISPR/Cas9-Mediated Treatment Ameliorates the Phenotype of the Epidermolytic
      Palmoplantar Keratoderma-like Mouse.
AB  - CRISPR/Cas9 has been confirmed as a distinctly efficient, simple-to-configure,
      highly specific genome-editing tool that has been used to treat monogenetic
      disorders. Epidermolytic palmoplantar keratoderma (EPPK) is a common autosomal
      dominant keratin disease resulting from dominant-negative mutation of the KRT9
      gene, and it has no effective therapy. We performed CRISPR/Cas9-mediated
      treatment on a knockin (KI) transgenic mouse model that carried a small indel
      heterozygous mutation of Krt9, c.434delAinsGGCT (p.Tyr144delinsTrpLeu), which
      caused a humanized EPPK-like phenotype. The mutation within exon 1 of Krt9
      generated a novel protospacer adjacent motif site, TGG, for Cas9 recognition and
      cutting. By delivering lentivirus vectors (LVs) encoding single-guide RNAs
      (sgRNAs) and Cas9 that targeted Krt9 sequence into HeLa cells engineered to
      constitutively express wild-type and mutant keratin 9 (K9), we found the sgRNA
      was highly effective in reducing expression of the mutant K9 protein in vitro. We
      injected the LV into the fore-paws of adult KI-Krt9 mice three times every 8 days
      and found that the expression of K9 decreased ~14.6%. The phenotypic mitigation
      was revealed by restoration of the abnormal differentiation and aberrant
      proliferation of the epidermis. Our data are the first to show that CRISPR/Cas9
      is a potentially powerful therapeutic option for EPPK and other PPK subtypes.

PMID- 30195763
TI  - One-Vector System for Multiplexed CRISPR/Cas9 against Hepatitis B Virus cccDNA
      Utilizing High-Capacity Adenoviral Vectors.
AB  - High-capacity adenoviral vectors (HCAdVs) devoid of all coding genes are powerful
      tools to deliver large DNA cargos into cells. Here HCAdVs were designed to
      deliver a multiplexed complete CRISPR/Cas9 nuclease system or a complete pair of
      transcription activator-like effector nucleases (TALENs) directed against the
      hepatitis B virus (HBV) genome. HBV, which remains a serious global health
      burden, forms covalently closed circular DNA (cccDNA) as a persistent DNA species
      in infected cells. This cccDNA promotes the chronic carrier status, and it
      represents a major hurdle in the treatment of chronic HBV infection. To date,
      only one study demonstrated viral delivery of a CRISPR/Cas9 system and a single
      guide RNA (gRNA) directed against HBV by adeno-associated viral (AAV) vectors.
      The advancement of this study is the co-delivery of multiple gRNA expression
      cassettes along with the Cas9 expression cassette in one HCAdV. Treatment of HBV
      infection models resulted in a significant reduction of HBV antigen production
      and the introduction of mutations into the HBV genome. In the transduction
      experiments, the HBV genome, including the HBV cccDNA, was degraded by the
      CRISPR/Cas9 system. In contrast, the combination of two parts of a TALEN pair in
      one vector could not be proven to yield an active system. In conclusion, we
      successfully delivered the CRISPR/Cas9 system containing three gRNAs using HCAdV,
      and we demonstrated its antiviral effect.

PMID- 30195762
TI  - LncRNA UCA1, Upregulated in CRC Biopsies and Downregulated in Serum Exosomes,
      Controls mRNA Expression by RNA-RNA Interactions.
AB  - Long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) contribute to the
      onset of many neoplasias through RNA-RNA competitive interactions; in addition,
      they could be secreted by cancer cells into biological fluids, suggesting their
      potential diagnostic application. By analyzing the expression of 17 lncRNAs and
      31 circRNAs in biopsies and serum exosomes from colorectal cancer (CRC) patients
      through qRT-PCR, we detected CCAT1, CCAT2, HOTAIR, and UCA1 upregulation and
      CDR1AS, MALAT1, and TUG1 downregulation in biopsies. In serum exosomes, UCA1 was
      downregulated, while circHIPK3 and TUG1 were upregulated. Combined receiver
      operating characteristic (ROC) curves of TUG1:UCA1 and circHIPK3:UCA1 showed high
      values of sensitivity and specificity. Through in vitro (i.e., RNA silencing and
      mitogen-activated protein kinase [MAPK] inhibition) and in silico analyses (i.e.,
      expression correlation and RNA-RNA-binding prediction), we found that UCA1 could
      (1) be controlled by MAPKs through CEBPB; (2) sequester miR-135a, miR-143, miR
      214, and miR-1271, protecting ANLN, BIRC5, IPO7, KIF2A, and KIF23 from microRNA
      (miRNA)-induced degradation; and (3) interact with mRNA 3'-UTRs, preventing miRNA
      binding. UCA1 and its co-regulated antisense LINC01764 could interact and
      reciprocally mask their own miRNA-binding sites. Functional enrichment analysis
      of the RNA-RNA network controlled by UCA1 suggested its potential involvement in
      cellular migration. The UCA1 regulatory axis would represent a promising target
      to develop innovative RNA-based therapeutics against CRC.

PMID- 30195764
TI  - miR-217 Promotes Cardiac Hypertrophy and Dysfunction by Targeting PTEN.
AB  - Previously, we found that the miR-217 expression level was increased in hearts
      from chronic heart failure (CHF) patients by using miRNA profile analysis. This
      study aimed to explore the role of miR-217 in cardiac dysfunction. Heart tissue
      samples from CHF patients were used to detect miR-217 expression levels. A type 9
      recombinant adeno-associated virus (rAAV9) was employed to manipulate miR-217
      expression in mice with thoracic aortic constriction (TAC)-induced cardiac
      dysfunction. Cardiac structure and function were measured by echocardiography and
      invasive pressure-volume analysis. The expression levels of miR-217 were
      increased in hearts from both CHF patients and TAC mice. Overexpression of miR
      217 in vivo aggravated pressure overload-induced cardiac hypertrophy, fibrosis,
      and cardiac dysfunction, whereas miR-217-TUD-mediated downregulation of miR-217
      reversed these effects. PTEN was predicted and validated as a direct target of
      miR-217, and re-expression of PTEN attenuated miR-217-mediated cardiac
      hypertrophy and cardiac dysfunction. Importantly, cardiomyocyte-derived miR-217
      containing exosomes enhanced proliferation of fibroblasts in vitro. All of these
      findings show that miR-217 participates in cardiac hypertrophy and cardiac
      fibrosis processes through regulating PTEN, which suggests a promising
      therapeutic target for CHF.

PMID- 30195765
TI  - Inducing CCR5Delta32/Delta32 Homozygotes in the Human Jurkat CD4+ Cell Line and
      Primary CD4+ Cells by CRISPR-Cas9 Genome-Editing Technology.
AB  - C-C chemokine receptor type 5 (CCR5) is the main co-receptor for HIV entry into
      the target CD4+ cells, and homozygous CCR5Delta32/Delta32 cells are resistant to
      CCR5-tropic HIV infection. However, the CCR5Delta32/Delta32 homozygous donors in
      populations are rare. Here we developed a simple approach to induce
      CCR5Delta32/Delta32 homozygotes through CRISPR-Cas9 genome-editing technology.
      Designing a pair of single-guide RNA targeting the flank region of the
      CCR5Delta32 mutation locus, we applied the CRISPR-Cas9 and lentiviral packaging
      system to successfully convert wild-type CCR5 into CCR5Delta32/Delta32
      homozygotes in the human Jurkat CD4+ cell line and primary CD4+ cells, exactly
      the same as the naturally occurring CCR5Delta32/Delta32 mutation. The successful
      rate is up to 20% in Jurkat cells but less in primary CD4+ cells. The modified
      CCR5Delta32/Delta32 CD4+ cells are resistant to CCR5-tropic HIV infection. Whole
      genome sequencing revealed no apparent off-target sites. This approach has the
      promise to promote HIV/AIDS therapy from the only cured unique Berlin patient to
      a routine autologous cell-based therapy.

PMID- 30195766
TI  - Removal of HIV DNA by CRISPR from Patient Blood Engrafts in Humanized Mice.
AB  - We used NOD/SCID mice, also known as NRG, to assess the ability of lentivirus
      mediated intravenous delivery of CRISPR in editing the HIV-1 genome from the
      circulating PBMC engrafts, some of which homed within several animal solid
      tissues. Lentivirus-mediated delivery of a multiplex of guide RNAs accompanied by
      Cas9 endonuclease led to the excision of the targeted region of the viral genome
      positioned within the HIV-1 LTR from the in-vitro-infected human peripheral blood
      mononuclear cells (PBMCs) embedded in the spleens of NRG mice. Similarly, the
      treatment of NRG mice harboring PBMC engrafts derived from HIV-1-positive
      patients with the therapeutic lentivirus eliminated the presence of the viral DNA
      fragment in the blood, as well as in the spleen, lung, and liver, of the
      engrafted animals. Sanger sequence analysis of the viral DNA after treatment with
      the lentiviral vectors expressing Cas9 and gRNAs verified the editing and removal
      of the proviral DNA fragment from the viral genome at the predicted sites. This
      proof-of-concept study, for the first time, demonstrates successful excision of
      the HIV-1 proviral DNA from patient immune cell engrafts in humanized mice upon
      treatment with lentivirus-expressing CRISPR and causes a decline in the level of
      replication-competent virus.

PMID- 30195768
TI  - Spliceosome-Mediated Pre-mRNA trans-Splicing Can Repair CEP290 mRNA.
AB  - Ocular gene therapy with recombinant adeno-associated virus (AAV) has shown
      vector-mediated gene augmentation to be safe and efficacious in the retina in one
      set of diseases (retinitis pigmentosa and Leber congenital amaurosis (LCA) caused
      by RPE65 deficiency), with excellent safety profiles to date and potential for
      efficacy in several additional diseases. However, size constraints imposed by the
      packaging capacity of the AAV genome restrict application to diseases with coding
      sequence lengths that are less than 5,000 nt. The most prevalent retinal diseases
      with monogenic inheritance are caused by mutations in genes that exceed this
      capacity. Here, we designed a spliceosome mediated pre-mRNA trans-splicing
      strategy to rescue expression of CEP290, which is associated with Leber
      congenital amaurosis type 10 (LCA10) and several syndromic diseases including
      Joubert syndrome. We used this reagent to demonstrate editing of CEP290 in cell
      lines in vitro and in vivo in a mini-gene mouse model. This study is the first to
      show broad editing of CEP290 transcripts and in vivo proof of concept for editing
      of CEP290 transcripts in photoreceptors and paves the way for future studies
      evaluating therapeutic effects.

PMID- 30195767
TI  - MicroRNA-206 Downregulation Improves Therapeutic Gene Expression and Motor
      Function in mdx Mice.
AB  - Duchenne muscular dystrophy (DMD) is a severe muscle-wasting disorder caused by a
      mutation in the dystrophin gene. Numerous gene therapies have been developed to
      replace or repair the defective dystrophin gene; however, these treatments cannot
      restore the full-length protein or completely resolve dystrophic symptoms.
      Secondary pathological mechanisms, such as functional ischemia and fibrosis, are
      thought to exacerbate the primary defect and cause the profound muscle
      degeneration found in dystrophic muscle. Surrogate therapies utilizing
      alternative therapeutic genes, or "booster genes," such as VEGFA and utrophin,
      seek to address these secondary mechanisms and have shown impressive benefit in
      mdx mice. A skeletal muscle-specific microRNA, miR-206, is particularly
      overexpressed in dystrophic muscle and inhibits the expression of known booster
      genes. Thus, we aimed to determine if miR-206 contributes to dystrophic pathology
      by repressing beneficial gene expression. Here, we show that AAV-mediated
      expression of a miR-206 decoy target effectively downregulated miR-206 expression
      and increased endogenous therapeutic gene expression in mature mdx muscle.
      Furthermore, treatment significantly improved motor function and dystrophic
      pathology in mdx mice. In summary, we have identified a contributing factor to
      the dystrophic phenotype and characterized a novel therapeutic avenue for DMD.

PMID- 30195769
TI  - EZH2-Mediated Epigenetic Suppression of GDF15 Predicts a Poor Prognosis and
      Regulates Cell Proliferation in Non-Small-Cell Lung Cancer.
AB  - Growth differentiation factor 15 (GDF15), a member of the TGF-beta superfamily of
      cytokines, has been reported to exert very heterogeneous functions in various
      tumors. However, its expression and roles in mediating non-small-cell lung cancer
      (NSCLC) progression remain unknown. In this study, we found that GDF15 is
      downregulated in paired NSCLC tissues and correlated with poor clinical outcomes
      in NSCLC. A functional experiment demonstrated that overexpression of GDF15
      significantly repressed NSCLC proliferation both in vitro and in vivo.
      Mechanistic studies reveal that inhibition of EZH2 expression prevented its
      binding to the GDF15 promoter region and reduced the trimethylation modification
      pattern of H3K27. Together, our data uncover that GDF15 is a direct target of
      EZH2 and, as a regulator of proliferation, might serve as a candidate prognostic
      biomarker and target for new therapies in human NSCLC.

PMID- 30195770
TI  - MiR-663a Stimulates Proliferation and Suppresses Early Apoptosis of Human
      Spermatogonial Stem Cells by Targeting NFIX and Regulating Cell Cycle.
AB  - Human spermatogonial stem cells (SSCs) could have significant applications in
      reproductive medicine and regenerative medicine because of their great
      plasticity. The fate determinations of human SSCs are mediated by epigenetic
      factors. However, nothing is known about the regulation of non-coding RNA on
      human SSCs. Here we have explored for the first time the expression, function,
      and target of miR-663a in human SSCs. MiR-663a was upregulated in human
      spermatogonia compared with pachytene spermatocytes, as indicated by microRNA
      microarray and real-time PCR. CCK-8 and 5-Ethynyl-2'-deoxyuridine (EDU) assays
      revealed that miR-663a stimulated cell proliferation and DNA synthesis of human
      SSCs. Annexin V and propidium iodide (PI) staining and flow cytometry
      demonstrated that miR-663a inhibited early and late apoptosis of human SSCs.
      Furthermore, NFIX was predicted and verified as a direct target of miR-663a. NFIX
      silencing led to an enhancement of cell proliferation and DNA synthesis and a
      reduction of the early apoptosis of human SSCs. NFIX silencing neutralized the
      influence of miR-663a inhibitor on the proliferation and apoptosis of human SSCs.
      Finally, both miR-663a mimics and NFIX silencing upregulated the levels of cell
      cycle regulators, including Cyclin A2, Cyclin B1, and Cyclin E1, whereas miR-663a
      inhibitor had an adverse effect. Knockdown of Cyclin A2, Cyclin B1, and Cyclin E1
      led to the decrease in the proliferation of human SSCs. Collectively, miR-663a
      has been identified as the first microRNA that promotes the proliferation and DNA
      synthesis and suppresses the early apoptosis of human SSCs by targeting NFIX via
      cell cycle regulators Cyclin A2, Cyclin B1, and Cyclin E1. This study thus
      provides novel insights into the molecular mechanisms underlying human
      spermatogenesis, and it could offer novel targets for treating male infertility
      and other human diseases.

PMID- 30195771
TI  - Thermoresponsive Bacteriophage Nanocarrier as a Gene Delivery Vector Targeted to
      the Gastrointestinal Tract.
AB  - The use of the gastrointestinal tract as a site for the local delivery of DNA is
      an exciting prospect. In order to obtain an effective vector capable of
      delivering a gene of interest to target cells to achieve sufficient and sustained
      transgene expression, with minimal toxicity, we developed a new generation of
      filamentous bacteriophage. This particular bacteriophage was genetically
      engineered to display an arginine-glycine-aspartic acid (RGD) motif (an integrin
      binding peptide) on the major coat protein pVIII and carry a mammalian DNA
      cassette. One unanticipated observation is the thermoresponsive behavior of
      engineered bacteriophage. This finding has led us to simplify the isolation
      method to purify bacteriophage particles from cell culture supernatant by low
      temperature precipitation. Our results showed that, in contrast to non-surface
      modified, the RGD-modified bacteriophage was successfully used to deliver a
      transgene to mammalian cells. Our in vitro model of the human intestinal follicle
      associated epithelium also demonstrated that bacteriophage particles were stable
      in simulated gastrointestinal fluids and able to cross the human intestinal
      barrier. In addition, we confirmed an adjuvant property of the engineered
      bacteriophage to induce nitric oxide production by macrophages. In conclusion,
      our study demonstrated the possibility of using bacteriophage for gene transfer
      in the gastrointestinal tract.

PMID- 30195772
TI  - ISO, via Upregulating MiR-137 Transcription, Inhibits GSK3beta-HSP70-MMP-2 Axis,
      Resulting in Attenuating Urothelial Cancer Invasion.
AB  - Our most recent studies demonstrate that miR-137 is downregulated in human
      bladder cancer (BC) tissues, while treatment of human BC cells with
      isorhapontigenin (ISO) elevates miR-137 abundance. Since ISO showed a strong
      inhibition of invasive BC formation in the N-butyl-N-(4-hydroxybutyl) nitrosamine
      (BBN)-induced invasive BC mouse model, the elucidation of a potential biological
      effect of miR-137 on antagonizing BC invasion and molecular mechanisms underlying
      ISO upregulation of miR-137 are very important. Here we discovered that ectopic
      expression of miR-137 led to specific inhibition of BC invasion in human high
      grade BC T24T and UMUC3 cells, while miR-137 deletion promoted the invasion of
      both cells, indicating the inhibitory effect of miR-137 on human BC invasion.
      Mechanistic studies revealed that ISO treatment induced miR-137 transcription by
      promoting c-Jun phosphorylation and, in turn, abolishing matrix metalloproteinase
      2 (MMP-2) abundance and invasion in BC cells. Moreover, miR-137 was able to
      directly bind to the 3' UTR of Glycogen synthase kinase-3beta (GSK3beta) mRNA and
      inhibit GSK3beta protein translation, consequently leading to a reduction of heat
      shock protein-70 (HSP70) translation via targeting the mTOR/S6 axis.
      Collectively, our studies discover an unknown function of miR-137, directly
      targeting the 3' UTR of GSK3beta mRNA and, thereby, inhibiting GSK3beta protein
      translation, mTOR/S6 activation, and HSP70 protein translation and, consequently,
      attenuating HSP70-mediated MMP-2 expression and invasion in human BC cells. These
      novel discoveries provide a deep insight into understanding the biomedical
      significance of miR-137 downregulation in invasive human BCs and the anti-cancer
      effect of ISO treatment on mouse invasive BC formation.

PMID- 30195773
TI  - A Synthetic Cross-Species CD200R1 Agonist Suppresses Inflammatory Immune
      Responses In Vivo.
AB  - Functional aptamers displaying agonistic or antagonistic properties are showing
      great promise as modulators of immune responses. Here, we report the development
      of a polyethylene glycol-modified (PEGylated) DNA aptamer as a cross-species
      (murine and human) CD200R1 agonist that modulates inflammatory responses in vivo.
      Specifically, DNA aptamers were discovered by performing independent SELEX
      searches on recombinant murine and human CD200R1. Aptamer motifs identified by
      next generation sequencing (NGS) were subsequently compared, leading to the
      discovery of motifs common to both targets. The CD200R1 DNA aptamer CCS13
      displayed the highest agonistic activity toward CD200R1 in terms of suppressing
      the induction of cytotoxic T-lymphocytes (CTLs) in both human and murine
      allogeneic-mixed lymphocyte cultures (allo-MLCs). A 20-kDa polyethylene glycol
      (PEG) chain was covalently attached to the 5' end of this aptamer, and the
      resulting conjugate was shown to block inflammatory responses in murine models of
      skin graft rejection and house-dust-mite-induced allergic airway inflammation.
      Importantly, this agonistic aptamer does not suppress CTL induction in 5-day allo
      MLCs with responder cells derived from CD200R1-/- mice, indicating that its mode
      of action is directly linked to CD200R1 activation. This study suggests that one
      can derive agonistic DNA aptamers that can be verified as immuno-modulators in
      murine models with outcomes potentially translatable to the treatment of human
      conditions.

PMID- 30195774
TI  - The Impact of lncRNA Dysregulation on Clinicopathology and Survival of Breast
      Cancer: A Systematic Review and Meta-analysis.
AB  - Dysregulation of multiple long non-coding RNAs (lncRNAs) was reported to play
      major roles in breast cancer (BC). Here we aimed to collect most of the relevant
      literature to assess the prognostic value of lncRNAs in BC. To this end, we
      systematically searched PubMed, Embase, Web of Science, Chinese National
      Knowledge Infrastructure (CNKI), and Wanfang to identify published articles on
      the associations of lncRNAs with clinicopathology and/or survival of BC. Via this
      searching, we identified 70 articles involving 9,307 BC patients and regarding 48
      lncRNAs. The expression of 41 lncRNAs was related to one or more
      clinicopathological parameters of BC, including tumor size; lymph node
      metastasis; histological grade; TNM stage; and estrogen receptor (ER),
      progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2)
      statuses (p < 0.05). Dysregulation of 28 lncRNAs was associated with overall
      survival, and abnormal expression of 9 lncRNAs was linked to disease-free
      survival. Furthermore, the expression level of 3 lncRNAs was correlated with
      metastasis-free survival, 3 lncRNAs with relapse-free survival, and 3 lncRNAs
      with progression-free survival. Our analysis showed that multiple lncRNAs were
      significantly associated with BC clinicopathology and survival. A large-scale
      study is needed to verify the prognostic value of these lncRNAs in BC.

PMID- 30195775
TI  - Ribosomal Protein S3 Gene Silencing Protects Against Cigarette Smoke-Induced
      Acute Lung Injury.
AB  - Chronic obstructive pulmonary disease (COPD) is estimated to be the third leading
      cause of death by 2030. Transcription factor NF-kappaB may play a critical role
      in COPD pathogenesis. Ribosomal protein S3 (RPS3), a 40S ribosomal protein
      essential for executing protein translation, has recently been found to interact
      with the NF-kappaB p65 subunit and promote p65 DNA-binding activity. We sought to
      study whether RPS3 gene silencing could protect against cigarette-smoke (CS)
      induced acute lung injury in a mouse model. Effects of an intratracheal RPS3
      siRNA in CS-induced lung injury were determined by measuring bronchoalveolar
      lavage (BAL) fluid cell counts, levels of inflammatory and oxidative damage
      markers, and NF-kappaB translocation. Lung RPS3 level was found to be upregulated
      for the first time with CS exposure, and RPS3 siRNA blocked CS-induced neutrophil
      counts in BAL fluid. RPS3 siRNA suppressed CS-induced lung inflammatory mediator
      and oxidative damage marker levels, as well as nuclear p65 accumulation and
      transcriptional activation. RPS3 siRNA was able to disrupt CS extract (CSE)
      induced NF-kappaB activation in an NF-kappaB reporter gene assay. We report for
      the first time that RPS3 gene silencing ameliorated CS-induced acute lung injury,
      probably via interruption of the NF-kappaB activity, postulating that RPS3 is a
      novel therapeutic target for COPD.

PMID- 30195776
TI  - Long Noncoding RNA 00473 Is Involved in Preeclampsia by LSD1 Binding-Regulated
      TFPI2 Transcription in Trophoblast Cells.
AB  - Preeclampsia (PE) is a syndrome manifested by high blood pressure that could
      develop in the latter half of pregnancy; however, the underlying mechanisms are
      not understood. Recent evidence points to the function of noncoding RNAs (ncRNAs)
      as novel regulators of the invasion, migration, proliferation, and apoptosis of
      trophoblasts involved in the development of placental vasculature. Here, we
      investigated the role of long intergenic ncRNA 00473 (linc00473) in PE and the
      associated molecular mechanisms. The expression of linc00473 was downregulated in
      the placenta of patients with severe PE as revealed by qRT-PCR analysis. In
      vitro, linc00473 knockdown in trophoblast cell lines HTR-8/SVneo, JAR, and JEG3
      significantly inhibited cell proliferation and promoted apoptosis, whereas
      linc00473 overexpression stimulated trophoblast proliferation. The mechanistic
      insights were provided by RNA-seq and qRT-PCR, which revealed that linc00473
      could regulate the transcription of genes relevant to cell growth, migration, and
      apoptosis. In particular, linc00473 inhibited the expression of tissue factor
      pathway inhibitor 2 (TFPI2) through binding to lysine-specific demethylase 1
      (LSD1). These results indicate that linc00473 could be involved in the
      pathogenesis and development of PE and may be a candidate biomarker as well as
      therapeutic target for this disease.

PMID- 30195777
TI  - Integrative Analysis of lncRNAs in Th17 Cell Lineage to Discover New Potential
      Biomarkers and Therapeutic Targets in Autoimmune Diseases.
AB  - Th17 cells play a critical role in the pathogenesis of autoimmune diseases,
      including multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus,
      Sjogren's syndrome, and inflammatory bowel disease. Despite the extensive
      investigation into this T cell lineage, little is understood regarding the role
      of Th17 lineage-specific lncRNAs (long non-coding RNAs) > 200 nt. lncRNAs may
      influence disease through a variety of mechanisms; their expression could be
      regulated by SNPs. lncRNAs can also affect the expression of neighboring genes or
      complementary miRNAs, and their expression may have lineage-specific patterns. In
      the system biology study presented here, the effective lncRNAs from different
      criteria were predicted for each autoimmune disease, and we then evaluated their
      expression levels in 50 MS patients compared to 25 controls using qRT-PCR. We
      identified changes in the expression levels of AL450992.2, AC009948.5, and RP11
      98D18.3 as potential peripheral blood mononuclear cell (PBMC) biomarkers for MS
      among our studied lncRNAs in which co-expression analysis of AL450992.2 had the
      most AUCs, and the relationship to RORC was also assessed. We propose that the
      recurrently deregulated lncRNAs identified in this report could provide a
      valuable resource for studies aimed at delineating the relationship between
      functional lncRNAs and autoimmune disorders.

PMID- 30195778
TI  - The Long Noncoding RNA D63785 Regulates Chemotherapy Sensitivity in Human Gastric
      Cancer by Targeting miR-422a.
AB  - Gastric cancer is one of the most prevalent tumor types in the world.
      Chemotherapy is the most common choice for cancer treatment. However,
      chemotherapy resistance and adverse side effects limit its clinical applications.
      Aberrant expression of long noncoding RNAs (lncRNAs) has been found in various
      stages of gastric cancer development and progression. In this study, we
      identified that an oncogenic lncRNA, long intergenic non-protein-coding RNA
      D63785 (lncR-D63785), is highly expressed in gastric cancer tissues and cells.
      Silencing of lncR-D63785 inhibited cell proliferation, cell migration and
      invasion in gastric cancer cell lines and reduced tumor volume and size in mice.
      We found that the expression of lncR-D63785 was inversely correlated with
      microRNA 422a (miR-422a) expression, which was involved in the downregulation of
      expression of myocyte enhancer factor-2D (MEF2D) and drug sensitivity. Knockdown
      of lncR-D63785 increased the expression of miR-422a and the sensitivity of
      gastric cancer cells to apoptosis induced by the anticancer drug doxorubicin
      (DOX). This indicates that lncR-D63785 acts as a competitive endogenous RNA
      (ceRNA) of miR-422a and promotes chemoresistance by blocking miR-422-dependent
      suppression of MEF2D. Together, our results suggest that the therapeutic
      suppression of lncR-D63785 alone or in combination with chemotherapeutic agents
      may be a promising strategy for treating gastric cancer.

PMID- 30195779
TI  - Morpholino Antisense Oligomers as a Potential Therapeutic Option for the
      Correction of Alternative Splicing in PMD, SPG2, and HEMS.
AB  - DNA variants of the proteolipid protein 1 gene (PLP1) that shift PLP1/DM20
      alternative splicing away from the PLP1 form toward DM20 cause the allelic X
      linked leukodystrophies Pelizaeus-Merzbacher disease (PMD), spastic paraplegia 2
      (SPG2), and hypomyelination of early myelinating structures (HEMS). We designed a
      morpholino oligomer (MO-PLP) to block use of the DM20 5' splice donor site,
      thereby shifting alternative splicing toward the PLP1 5' splice site. Treatment
      of an immature oligodendrocyte cell line with MO-PLP significantly shifted
      alternative splicing toward PLP1 expression from the endogenous gene and from
      transfected human minigene splicing constructs harboring patient variants known
      to reduce the amount of the PLP1 spliced product. Additionally, a single
      intracerebroventricular injection of MO-PLP into the brains of neonatal mice,
      carrying a deletion of an intronic splicing enhancer identified in a PMD patient
      that reduces the Plp1 spliced form, corrected alternative splicing at both RNA
      and protein levels in the CNS. The effect lasted to post-natal day 90, well
      beyond the early post-natal spike in myelination and PLP production. Further, the
      single injection produced a sustained reduction of inflammatory markers in the
      brains of the mice. Our results suggest that morpholino oligomers have
      therapeutic potential for the treatment of PMD, SPG2, and HEMS.

PMID- 30195781
TI  - Effects of RANKL Knockdown by Virus-like Particle-Mediated RNAi in a Rat Model of
      Osteoporosis.
AB  - Rebalancing of the RANKL/OPG system seems to be an effective treatment strategy
      in postmenopausal osteoporosis. Here, we evaluate the knockdown of RANKL by in
      vivo-delivered siRNA in a rat model of osteoporosis. Virus-like-particles (VLPs)
      derived from polyoma JC virus were used for delivering RANKL siRNA in
      ovariectomized (OVX) rats. 48 rats were ovariectomized and treated with either
      17beta-estradiol (E2), VLPs containing RANKL siRNA (siRANKL), or VLPs containing
      non-cognate siRNA (siCtrl). All OVX groups were subdivided into the prophylaxis
      group (PG) and the therapy group (TG). The PG received treatment directly after
      being OVX for 10 weeks. The TG received treatment 5 weeks after being OVX for 5
      weeks. Rats were sacrificed 10 weeks after being OVX. Bone and blood samples were
      analyzed. E2 and siRANKL showed a significant knockdown of RANKL mRNA. A protein
      knockdown was observed with E2 and siRANKL in the TG but not in the PG. No
      distinct improvements in biomechanical and morphological properties of the bones
      were observed after siRANKL treatment. In the PG, E2 protected the bone
      structure. We demonstrated successful mRNA and protein knockdown by VLP-mediated
      RNAi in vivo. Knockdown of membranous RANKL did not result in significant
      improvements of bone properties in this model of early-stage postmenopausal
      osteoporosis.

PMID- 30195780
TI  - Implications of Newly Identified Brain eQTL Genes and Their Interactors in
      Schizophrenia.
AB  - Schizophrenia (SCZ) is a devastating genetic mental disorder. Identification of
      the SCZ risk genes in brains is helpful to understand this disease. Thus, we
      first used the minimum Redundancy-Maximum Relevance (mRMR) approach to integrate
      the genome-wide sequence analysis results on SCZ and the expression quantitative
      trait locus (eQTL) data from ten brain tissues to identify the genes related to
      SCZ. Second, we adopted the variance inflation factor regression algorithm to
      identify their interacting genes in brains. Third, using multiple analysis
      methods, we explored and validated their roles. By means of the aforementioned
      procedures, we have found that (1) the cerebellum may play a crucial role in the
      pathogenesis of SCZ and (2) ITIH4 may be utilized as a clinical biomarker for the
      diagnosis of SCZ. These interesting findings may stimulate novel strategy for
      developing new drugs against SCZ. It has not escaped our notice that the approach
      reported here is of use for studying many other genome diseases as well.

PMID- 30195782
TI  - RNA Aptamers Rescue Mitochondrial Dysfunction in a Yeast Model of Huntington's
      Disease.
AB  - Huntington's disease (HD) is associated with the misfolding and aggregation of
      mutant huntingtin harboring an elongated polyglutamine stretch at its N terminus.
      A distinguishing pathological hallmark of HD is mitochondrial dysfunction. Any
      strategy that can restore the integrity of the mitochondrial environment should
      have beneficial consequences for the disease. Specific RNA aptamers were selected
      that were able to inhibit aggregation of elongated polyglutamine stretch
      containing mutant huntingtin fragment (103Q-htt). They were successful in
      reducing the calcium overload, which leads to mitochondrial membrane
      depolarization in case of HD. In one case, the level of Ca2+ was restored to the
      level of cells not expressing 103Q-htt, suggesting complete recovery. The
      presence of aptamers was able to increase mitochondrial mass in cells expressing
      103Q-htt, along with rescuing loss of mitochondrial genome. The oxidative damage
      to the proteome was prevented, which led to increased viability of cells, as
      monitored by flow cytometry. Thus, the presence of aptamers was able to inhibit
      aggregation of mutant huntingtin fragment and restore mitochondrial dysfunction
      in the HD cell model, confirming the advantage of the strategy in a disease
      relevant parameter.

PMID- 30195783
TI  - VSV-G-Enveloped Vesicles for Traceless Delivery of CRISPR-Cas9.
AB  - The method of delivery of CRISPR-Cas9 into target cells is a strong determinant
      of efficacy and specificity in genome editing. Even though high efficiency of
      Cas9 delivery is necessary for optimal editing, its long-term and high levels of
      expression correlate with increased off-target activity. We developed vesicles
      (VEsiCas) carrying CRISPR-SpCas9 ribonucleoprotein complexes (RNPs) that are
      efficiently delivered into target cells through the fusogenic glycoprotein of the
      vesicular stomatitis virus (VSV-G). A crucial step for VEsiCas production is the
      synthesis of the single guide RNA (sgRNA) mediated by the T7 RNA polymerase in
      the cytoplasm of producing cells as opposed to canonical U6-driven Pol III
      nuclear transcription. In VEsiCas, the absence of DNA encoding SpCas9 and sgRNA
      allows rapid clearance of the nuclease components in target cells, which
      correlates with reduced genome-wide off-target cleavages. Compared with SpCas9
      RNPs electroporation, which is currently the method of choice to obtain transient
      SpCas9 activity, VEsiCas deliver the nuclease with higher efficiency and lower
      toxicity. We show that a wide variety of cells can be edited through VEsiCas,
      including a variety of transformed cells, induced pluripotent stem cells (iPSCs),
      and cardiomyocytes, in vivo. VEsiCas is a traceless CRISPR-Cas9 delivery tool for
      efficient and safe genome editing that represents a further advancement toward
      the therapeutic use of the CRISPR-Cas9 technology.

PMID- 30195785
TI  - Long-Term Morpholino Oligomers in Hexose Elicits Long-Lasting Therapeutic
      Improvements in mdx Mice.
AB  - Approval of antisense oligonucleotide eteplirsen highlights the promise of exon
      skipping therapeutics for Duchenne muscular dystrophy patients. However, the
      limited efficacy of eteplirsen underscores the importance to improve systemic
      delivery and efficacy. Recently, we demonstrated that a glucose and fructose (GF)
      delivery formulation effectively potentiates phosphorodiamidate morpholino
      oligomer (PMO). Considering the clinical potential of GF, it is important to
      determine the long-term compatibility and efficacy with PMO in mdx mice prior to
      clinical translation. Here, we report that yearlong administration of a
      clinically applicable PMO dose (50 mg/kg/week for 3 weeks followed by 50
      mg/kg/month for 11 months) with GF elicited sustainably high levels of dystrophin
      expression in mdx mice, with up to 45% of the normal level of dystrophin restored
      in most peripheral muscles without any detectable toxicity. Importantly, PMO-GF
      resulted in phenotypical rescue and mitochondrial biogenesis with functional
      improvement. Carbohydrate metabolites measurements revealed improved metabolic
      and energetic conditions after PMO-GF treatment in mdx mice without metabolic
      anomaly. Collectively, our study shows PMO-GF's ability to elicit long-lasting
      therapeutic effects with tolerable toxicity and represents a new treatment
      modality for Duchenne muscular dystrophy, and provides guidelines for antisense
      oligonucleotides with GF in clinical use.

PMID- 30195784
TI  - miR-7 Modulates hESC Differentiation into Insulin-Producing Beta-like Cells and
      Contributes to Cell Maturation.
AB  - Human pluripotent stem cells retain the extraordinary capacity to differentiate
      into pancreatic beta cells. For this particular lineage, more effort is still
      required to stress the importance of developing an efficient, reproducible, easy,
      and cost-effective differentiation protocol to obtain more mature, homogeneous,
      and functional insulin-secreting cells. In addition, microRNAs (miRNAs) have
      emerged as a class of small non-coding RNAs that regulate many cellular
      processes, including pancreatic differentiation. Some miRNAs are known to be
      preferentially expressed in islets. Of note, miR-375 and miR-7 are two of the
      most abundant pancreatic miRNAs, and they are necessary for proper pancreatic
      islet development. Here we provide new insight into specific miRNAs involved in
      pancreatic differentiation. We found that miR-7 is differentially expressed
      during the differentiation of human embryonic stem cells (hESCs) into a beta cell
      like phenotype and that its modulation plays an important role in generating
      mature pancreatic beta cells. This strategy may be exploited to optimize the
      potential for in vitro differentiation of hESCs into insulin-producing beta-like
      cells for use in preclinical studies and future clinical applications as well as
      the prospective uses of miRNAs to improve this process.

PMID- 30195786
TI  - Impact of miRNA-mRNA Profiling and Their Correlation on Medulloblastoma
      Tumorigenesis.
AB  - Medulloblastoma (MB) is a clinically challenging, childhood brain tumor with a
      diverse genetic makeup and differential miRNA profile. Aiming to identify
      deregulated miRNAs in MB, the miRNA expression profile of human MB samples was
      compared to that of normal cerebellar tissues. As a result, 8 upregulated and 64
      downregulated miRNAs were identified in MB samples. Although various algorithms
      have been developed to predict the interaction between miRNA-mRNA pairs, the
      complexity and fidelity of miRNA-mRNA remain a concern. Therefore, to identify
      the signatures of miRNA-mRNA interactions essential for MB pathogenesis, miRNA
      profiling, RNA sequencing, and ingenuity pathway analysis (IPA) were performed in
      the same primary human MB samples. Further, when miR-217 was inhibited, a
      significant upregulation of predicted target genes SIRT1, ROBO1, FOXO3, and SMAD7
      in HDMB03 cells was observed, confirming the validity of our approach. Functional
      analysis revealed that the inhibition of miR-217 in HDMB03 cells suppresses
      colony formation, migration, invasion, promoted apoptosis, and arrested cell
      population in S phase, indicating that manipulation of miR-217 may have a
      therapeutic potential for MB patients. Therefore, our study provides an essential
      platform for future investigations of specific miRNAs responsible for MB
      pathogenesis.

PMID- 30195787
TI  - Self-Crosslinking Lipopeptide/DNA/PEGylated Particles: A New Platform for DNA
      Vaccination Designed for Assembly in Aqueous Solution.
AB  - Delivery of plasmids for gene expression in vivo is an inefficient process that
      requires improvement and optimization to unlock the clinical potential of DNA
      vaccines. With ease of manufacture and biocompatibility in mind, we explored
      condensation of DNA in aqueous solution with a self-crosslinking, endosome
      escaping lipopeptide (LP), stearoyl-Cys-His-His-Lys-Lys-Lys-amide (stearoyl
      CH2K3), to produce cationic LP/DNA complexes. To test whether poly(ethylene
      glycol) (PEG)-ylation of these cationic complexes to neutralize the surface
      charge would improve the distribution, gene expression, and immune responses
      poly(ethylene glycol), these LP/DNA complexes were combined with 1,2-distearoyl
      sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE
      PEG2000). Fluorescence imaging illustrated that the cationic complexes exhibited
      the highest degree of localization and lowest degree of dispersion throughout the
      injected muscle, suggesting impaired mobility of cationic particles upon
      administration. Nanoluciferase reporter assays over a 90-day period demonstrated
      that gene expression levels in muscle were highest for PEGylated particles, with
      over a 200-fold higher level of expression than the cationic particles observed
      at 30 days. Humoral and cell-mediated immune responses were evaluated in vivo
      after injection of an ovalbumin expression plasmid. PEGylation improved both
      immune responses to the DNA complexes in mice. Overall, this suggests that
      PEGylation of cationic lipopeptide complexes can significantly improve both the
      transgene expression and immunogenicity of intramuscular DNA vaccines.

PMID- 30195788
TI  - Recurrence-Associated Long Non-coding RNA Signature for Determining the Risk of
      Recurrence in Patients with Colon Cancer.
AB  - Patients with colon cancer are often faced a high risk of disease recurrence
      within 5 years of treatment that is the major cause of cancer mortality. Reliable
      molecular markers were required to improve the most effective personalized
      therapy. Here, we identified a recurrence-associated six-lncRNA (long non-coding
      RNA) signature (LINC0184, AC105243.1, LOC101928168, ILF3-AS1, MIR31HG, and
      AC006329.1) that can effectively distinguish between high and low risk of cancer
      recurrence from 389 patients of a discovery dataset, and validated its robust
      performance in four independent datasets comprising a total of 906 colon cancer
      patients. We found that the six-lncRNA signature was an independent predictive
      factor of disease recurrence in multivariate analysis and was superior to the
      performance of clinical factors and known gene signature. Furthermore, in silico
      functional analysis showed that the six-lncRNA-signature-associated coding genes
      are significantly enriched in proliferation and angiogenesis, cell death, as well
      as critical cancer pathways that could play important roles in colon cancer
      recurrence. Together, the six-lncRNA signature holds great potential for
      recurrence risk assessment and personalized management of colon cancer patients.

PMID- 30195789
TI  - Uridine Depletion and Chemical Modification Increase Cas9 mRNA Activity and
      Reduce Immunogenicity without HPLC Purification.
AB  - The Cas9/guide RNA (Cas9/gRNA) system is commonly used for genome editing. mRNA
      expressing Cas9 can induce innate immune responses, reducing Cas9 expression.
      First-generation Cas9 mRNAs were modified with pseudouridine and 5-methylcytosine
      to reduce innate immune responses. We combined four approaches to produce more
      active, less immunogenic second-generation Cas9 mRNAs. First, we developed a
      novel co-transcriptional capping method yielding natural Cap 1. Second, we
      screened modified nucleotides in Cas9 mRNA to identify novel modifications that
      increase Cas9 activity. Third, we depleted the mRNA of uridines to improve mRNA
      activity. Lastly, we tested high-performance liquid chromatography (HPLC)
      purification to remove double-stranded RNAs. The activity of these mRNAs was
      tested in cell lines and primary human CD34+ cells. Cytokines were measured in
      whole blood and mice. These approaches yielded more active and less immunogenic
      mRNA. Uridine depletion (UD) most impacted insertion or deletion (indel)
      activity. Specifically, 5-methoxyuridine UD induced indel frequencies as high as
      88% (average +/- SD = 79% +/- 11%) and elicited minimal immune responses without
      needing HPLC purification. Our work suggests that uridine-depleted Cas9 mRNA
      modified with 5-methoxyuridine (without HPLC purification) or pseudouridine may
      be optimal for the broad use of Cas9 both in vitro and in vivo.

PMID- 30195790
TI  - Gemcitabine-Incorporated G-Quadruplex Aptamer for Targeted Drug Delivery into
      Pancreas Cancer.
AB  - Gemcitabine has been considered a first-line chemotherapy agent for the treatment
      of pancreatic cancer. However, the initial response rate of gemcitabine is low
      and chemoresistance occurs frequently. Aptamers can be effectively internalized
      into cancer cells via binding to target molecules with high affinity and
      specificity. In the current study, we constructed an aptamer-based gemcitabine
      delivery system, APTA-12, and assessed its therapeutic effects on pancreatic
      cancer cells in vitro and in vivo. APTA-12 was effective in vitro and in vivo in
      pancreatic cancer cells with high expression of nucleolin. The results of in
      vitro cytotoxicity assays indicated that APTA-12 inhibited the growth of
      pancreatic cancer cell lines. In vivo evaluation showed that APTA-12 effectively
      inhibited the growth of pancreatic cancer in Capan-1 tumor-bearing mice compared
      to mice that received gemcitabine alone or vehicle. These results suggest that
      the gemcitabine-incorporated APTA-12 aptamer may be a promising targeted
      therapeutic strategy for pancreatic cancer.

PMID- 30195791
TI  - Ex Vivo COL7A1 Correction for Recessive Dystrophic Epidermolysis Bullosa Using
      CRISPR/Cas9 and Homology-Directed Repair.
AB  - Recessive dystrophic epidermolysis bullosa is a rare and severe genetic skin
      disease resulting in blistering of the skin and mucosa. Recessive dystrophic
      epidermolysis bullosa (RDEB) is caused by a wide variety of mutations in COL7A1
      encoding type VII collagen, which is essential for dermal-epidermal adhesion.
      Here we demonstrate the feasibility of ex vivo COL7A1 editing in primary RDEB
      cells and in grafted 3D skin equivalents through CRISPR/Cas9-mediated homology
      directed repair. We designed five guide RNAs to correct a RDEB causative null
      mutation in exon 2 (c.189delG; p.Leu64Trpfs*40). Among the site-specific guide
      RNAs tested, one showed significant cleavage activity in primary RDEB
      keratinocytes and in fibroblasts when delivered as integration-deficient
      lentivirus. Genetic correction was detected in transduced keratinocytes and
      fibroblasts by allele-specific highly sensitive TaqMan-droplet digital PCR
      (ddPCR), resulting in 11% and 15.7% of corrected COL7A1 mRNA expression,
      respectively, without antibiotic selection. Grafting of genetically corrected 3D
      skin equivalents onto nude mice showed up to 26% re-expression and normal
      localization of type VII collagen as well as anchoring fibril formation at the
      dermal-epidermal junction. Our study provides evidence that precise genome
      editing in primary RDEB cells is a relevant strategy to genetically correct
      COL7A1 mutations for the development of future ex vivo clinical applications.

PMID- 30195792
TI  - Hepatocyte Growth Factor Regulates the miR-206-HDAC4 Cascade to Control
      Neurogenic Muscle Atrophy following Surgical Denervation in Mice.
AB  - Hepatocyte growth factor (HGF) has been well characterized for its roles in the
      migration of muscle progenitors during embryogenesis and the differentiation of
      muscle stem cells, but its function in adult neurogenic muscle atrophic
      conditions is poorly understood. Here we investigated whether HGF/c-met signaling
      has any effects on muscle-atrophic conditions. It was found that HGF expression
      was upregulated in skeletal muscle tissue following surgical denervation and in
      hSOD1-G93A transgenic mice showing severe muscle loss. Pharmacological inhibition
      of the c-met receptor decreased the expression level of pri-miR-206, enhanced
      that of HDAC4 and atrogenes, and resulted in increased muscle atrophy. In C2C12
      cells, HGF inhibited phosphorylation of Smad3 and relieved TGF-beta-mediated
      suppression of miR-206 expression via JNK. When extra HGF was exogenously
      provided through intramuscular injection of plasmid DNA expressing HGF, the
      extent of muscle atrophy was reduced, and the levels of all affected biochemical
      markers were changed accordingly, including those of primary and mature miR-206,
      HDAC4, and various atrogenes. Taken together, our finding suggested that HGF
      might play an important role in regard to neurogenic muscle atrophy and that HGF
      might be used as a platform to develop therapeutic agents for neuromuscular
      disorders.

PMID- 30195793
TI  - MicroRNA-125b Promotes Hepatic Stellate Cell Activation and Liver Fibrosis by
      Activating RhoA Signaling.
AB  - miR-125b is frequently dysregulated in different diseases. Activation of hepatic
      stellate cells (HSCs) is a critical event during liver fibrogenesis. However, the
      function and its underlying mechanism of miR-125b in HSC activation and liver
      fibrosis are still unknown. Here, we showed that miR-125b was upregulated in
      HSCs, but not in hepatocytes, during hepatic fibrogenesis in vivo and upon
      culture activation in vitro. Inhibition of miR-125b suppressed the expression of
      profibrogenic genes in culture-activated primary HSCs and reduced the basal and
      transforming growth factor beta (TGF-beta)-induced alpha-smooth muscle actin
      (alpha-SMA) expression and cell contraction of the immortalized HSC cell line. In
      contrast, ectopic expression of miR-125b promoted alpha-SMA expression and HSC
      contraction. Moreover, antagonizing miR-125b in vivo significantly alleviated
      liver fibrosis in CCl4-treated mice. Mechanistically, overexpression of miR-125b
      in HSCs enhanced RhoA activity by directly targeting StAR-related lipid transfer
      (START) domain containing 13 (Stard13), a RhoA-specific GTPase-activating
      protein, whereas knockdown of miR-125b abrogated RhoA activation. Furthermore,
      inhibition of RhoA or its downstream molecules, Mrtf-A and Srf, attenuated the
      miR-125b-induced alpha-SMA expression and HSC contraction. Therefore, our
      findings identify a miR-125b-Stard13-RhoA-alpha-SMA signaling cascade in HSCs and
      highlight its importance in hepatic fibrosis.

PMID- 30195795
TI  - DROSHA Knockout Leads to Enhancement of Viral Titers for Vectors Encoding miRNA
      Adapted shRNAs.
AB  - RNAi-based gene therapy using miRNA-adapted short hairpin RNAs (shRNAmiR) is a
      powerful approach to modulate gene expression. However, we have observed low
      viral titers with shRNAmiR-containing recombinant vectors and hypothesized that
      this could be due to cleavage of viral genomic RNA by the endogenous
      microprocessor complex during virus assembly. To test this hypothesis, we
      targeted DROSHA, the core component of the microprocessor complex, and
      successfully generated monoallelic and biallelic DROSHA knockout (KO) HEK293T
      cells for vector production. DROSHA KO was verified by polymerase chain reaction
      (PCR) and western blot analysis. We produced lentiviral vectors containing Venus
      with or without shRNA hairpins and generated virus supernatants using DROSHA KO
      packaging cells. We observed an increase in the fluorescence intensity of hairpin
      containing Venus transcripts in DROSHA KO producer cells consistent with reduced
      microprocessor cleavage of encoded mRNA transcripts, and recovery in the viral
      titer of hairpin-containing vectors compared with non-hairpin-containing
      constructs. We confirmed the absence of significant shRNAmiR processing by
      northern blot analysis and showed that this correlated with an increase in the
      amount of full-length vector genomic RNA. These findings may have important
      implications in future production of viral shRNAmiR-containing vectors for RNAi
      based therapy.

PMID- 30195794
TI  - A Novel Mechanism of Doxorubicin Resistance and Tumorigenesis Mediated by
      MicroRNA-501-5p-Suppressed BLID.
AB  - Doxorubicin is a widely used anthracycline-based anti-tumor agent for both solid
      and liquid tumors. Mounting evidence has demonstrated that microRNAs (miRNAs) are
      involved in chemoresistance and tumorigenesis. However, the roles of microRNA-501
      5p (miR-501) in doxorubicin resistance and gastric cancer cell proliferation and
      invasion are still not fully understood. In this study, we identified that BLID
      (BH3-like motif-containing protein, cell death inducer) was directly regulated by
      miR-501 at the post-transcriptional level in multiple gastric cancer cell lines.
      Endogenous miR-501 was higher, whereas BLID was lower, in doxorubicin-resistant
      gastric cancer SGC7901/ADR cells compared with their parental SGC7901 cells. miR
      501 suppressed gastric cancer cell apoptosis, induced resistance to doxorubicin,
      and enhanced cell proliferation, migration, and invasion. Subcutaneous injection
      of miR-501 lentivirus-infected SGC7901 cells resulted in rapid growth of
      xenograft tumors and resistance to doxorubicin treatment, unlike injection of
      negative miRNA lentivirus-infected SGC7901 cells. This is achieved at least
      partially by directly targeting BLID and subsequent inactivation of caspase-9 and
      caspase-3 and phosphorylation of Akt. Taken together, miR-501 induces doxorubicin
      resistance and enhances the tumorigenesis of gastric cancer cells by suppressing
      BLID. miR-501 might be a potential target for doxorubicin resistance and gastric
      cancer therapy.

PMID- 30195796
TI  - Elevated Tristetraprolin Impairs Trophoblast Invasion in Women with Recurrent
      Miscarriage by Destabilization of HOTAIR.
AB  - Tristetraprolin (TTP) regulates the stability of multiple targets that have
      important biological roles. However, the role of TTP in trophoblasts at the
      maternal-fetal interface remains poorly understood. We demonstrated that TTP was
      upregulated in placental trophoblasts from patients with recurrent miscarriages
      (RMs). Immunofluorescence and immunoblotting analyses indicated that TTP was
      redistributed from the nucleus to the cytoplasm in trophoblasts from patients
      with RMs. Trophoblast invasion and proliferation was repressed by TTP
      overexpression and was enhanced by TTP knockdown. Interestingly, TTP knockdown
      promoted trophoblast invasion in an ex vivo explant culture model. Furthermore,
      TTP overexpression in trophoblasts significantly inhibited the expression of the
      long non-coding RNA (lncRNA) HOTAIR. TTP was found to regulate HOTAIR expression
      by a posttranscriptional mechanism. To RNA immunoprecipitation (RIP) and RNA
      protein, pull-down identified TTP as a specific binding partner that decreased
      the half-life of HOTAIR and lowered steady-state HOTAIR expression levels,
      indicating a novel posttranscriptional regulatory mechanism. Our findings
      identify a novel function for TTP in lncRNA regulation and provide important
      insights into the regulation of lncRNA expression. This study reveals a new
      pathway governing the regulation of TTP/HOTAIR in trophoblast cell invasion
      during early pregnancy.

PMID- 30195797
TI  - Long Non-coding RNA Profiling Reveals an Abundant MDNCR that Promotes
      Differentiation of Myoblasts by Sponging miR-133a.
AB  - Muscle development is regulated by a series of complicate processes, and non
      coding RNAs (ncRNAs) such as lncRNA have been reported to play important roles in
      regulating skeletal myogenesis and diseases. Here we profile the expression of
      lncRNA in cattle skeletal muscle tissue from fetus and adult developmental stages
      and detect 13,580 lncRNA candidates. Many of these lncRNAs are differentially
      expressed between two developmental stages. We further characterize one abundant
      lncRNA with the highest expression level of all downregulated lncRNAs, which we
      named muscle differentiation-associated lncRNA (MDNCR). Via luciferase screening,
      RNA binding protein immunoprecipitation (RIP), and RNA pull-down assays, MDNCR
      was observed to directly bind to miR-133a with 32 potential binding sites. GosB
      was identified as a target of miR-133a by luciferase activity, quantitative real
      time qPCR, and western blotting assays. Overexpression of MDNCR increased the
      expression of GosB, whereas this effect was abolished by miR-133a. We found that
      MDNCR promotes myoblast differentiation and inhibits cell proliferation by
      sponging miR-133a. These results demonstrate that MDNCR binding miR-133a promotes
      cell differentiation by targeting GosB in cattle primary myoblasts.

PMID- 30195798
TI  - Zinc-Finger Nucleases Induced by HIV-1 Tat Excise HIV-1 from the Host Genome in
      Infected and Latently Infected Cells.
AB  - Highly active anti-retroviral therapy (HAART) cannot clear infected cells
      harboring HIV-1 proviral DNA from HIV-1-infected patients. We previously
      demonstrated that zinc-finger nucleases (ZFNs) can specifically and efficiently
      excise HIV-1 proviral DNA from latently infected human T cells by targeting long
      terminal repeats (LTRs), a novel and alternative antiretroviral strategy for
      eradicating HIV-1 infection. To prevent unwanted off-target effects from
      constantly expressed ZFNs, in this study, we engineered the expression of ZFNs
      under the control of HIV-1 LTR, by which ZFN expression can be activated by the
      HIV-1 (Trans-Activator of Transcription) Tat protein. Our results show that
      functional expression of ZFNs induced by Tat excise the integrated proviral DNA
      of HIV-NL4-3-eGFP in approximately 30% of the population of HIV-1-infected cells.
      The results from HIV-1-infected human primary T cells and latently infected T
      cells treated with the inducible ZFNs further validated that proviral DNA can be
      excised. Taken together, positively regulated expression of ZFNs in the presence
      of HIV-1 Tat may provide a safer and novel implementation of genome-editing
      technology for eradicating HIV-1 proviral DNA from infected host cells.

PMID- 30195799
TI  - Translating SOD1 Gene Silencing toward the Clinic: A Highly Efficacious, Off
      Target-free, and Biomarker-Supported Strategy for fALS.
AB  - Of familial amyotrophic lateral sclerosis (fALS) cases, 20% are caused by
      mutations in the gene encoding human cytosolic Cu/Zn superoxide dismutase
      (hSOD1). Efficient translation of the therapeutic potential of RNAi for the
      treatment of SOD1-ALS patients requires the development of vectors that are free
      of significant off-target effects and with reliable biomarkers to discern
      sufficient target engagement and correct dosing. Using adeno-associated virus
      serotype 9 to deliver RNAi against hSOD1 in the SOD1G93A mouse model, we found
      that intrathecal injection of the therapeutic vector via the cisterna magna
      delayed onset of disease, decreased motor neuron death at end stage by up to 88%,
      and prolonged the median survival of SOD1G93A mice by up to 42%. To our
      knowledge, this is the first report to demonstrate no significant off-target
      effects linked to hSOD1 silencing, providing further confidence in the
      specificity of this approach. We also report the measurement of cerebrospinal
      fluid (CSF) hSOD1 protein levels as a biomarker of effective dosing and efficacy
      of hSOD1 knockdown. Together, these data provide further confidence in the safety
      of the clinical therapeutic vector. The CSF biomarker will be a useful measure of
      biological activity for translation into human clinical trials.

PMID- 30195801
TI  - Lung endothelial cell-targeted peptide-guided bFGF promotes the regeneration
      after radiation induced lung injury.
AB  - Basic fibroblast growth factor (bFGF) can protect the lung against radiation
      induced pulmonary vascular endothelial apoptosis and subsequent radiation-induced
      lung injury (RILI). However, guiding bFGF to pulmonary vascular endothelial cells
      is a key determinant for the success of bFGF therapy. To improve the lung
      targeting ability of bFGF, a lung endothelial cell-targeting peptide was fused to
      bFGF (LET-bFGF). An in vitro biological activity assay indicated that fusion of
      LET did not affect the bioactivity of bFGF. In addition, the fused protein showed
      superior lung-targeting ability following intravenous injection. Upon injecting
      LET-bFGF intravenously after thorax radiation, LET-bFGF could better protect
      against pulmonary vascular endothelial cell apoptosis as early as 4 h post
      radiation. Compared with native bFGF, enhanced therapeutic effects of LET-bFGF
      were also observed in terms of decreased vascular abnormalities, disorganized
      lung structure, inflammatory cell migration, and lung density at 2 months post
      radiation. Therefore, lung endothelial cell-targeted bFGF may represent a
      promising remedy for RILI.

PMID- 30195800
TI  - Priming Human Repopulating Hematopoietic Stem and Progenitor Cells for Cas9/sgRNA
      Gene Targeting.
AB  - Engineered nuclease-mediated gene targeting through homologous recombination (HR)
      in hematopoietic stem and progenitor cells (HSPCs) has the potential to treat a
      variety of genetic hematologic and immunologic disorders. Here, we identify
      critical parameters to reproducibly achieve high frequencies of RNA-guided
      (single-guide RNA [sgRNA]; CRISPR)-Cas9 nuclease (Cas9/sgRNA) and rAAV6-mediated
      HR at the beta-globin (HBB) locus in HSPCs. We identified that by transducing
      HSPCs with rAAV6 post-electroporation, there was a greater than 2-fold
      electroporation-aided transduction (EAT) of rAAV6 endocytosis with roughly 70% of
      the cell population having undergone transduction within 2 hr. When HSPCs are
      cultured at low densities (1 * 105 cells/mL) prior to HBB targeting, HSPC
      expansion rates are significantly positively correlated with HR frequencies in
      vitro as well as in repopulating cells in immunodeficient NSG mice in vivo. We
      also show that culturing fluorescence-activated cell sorting (FACS)-enriched HBB
      targeted HSPCs at low cell densities in the presence of the small molecules,
      UM171 and SR1, stimulates the expansion of gene-edited HSPCs as measured by
      higher engraftment levels in immunodeficient mice. This work serves not only as
      an optimized protocol for genome editing HSPCs at the HBB locus for the treatment
      of beta-hemoglobinopathies but also as a foundation for editing HSPCs at other
      loci for both basic and translational research.

PMID- 30195802
TI  - A novel galactose-PEG-conjugated biodegradable copolymer is an efficient gene
      delivery vector for immunotherapy of hepatocellular carcinoma.
AB  - Successful immunogene therapy depends not only on the therapeutic gene but also
      on the gene delivery vector. In this study, we synthesized a novel copolymer
      consisting of low-molecular-weight polyethylenimine (PEI) cross-linked by myo
      inositol (INO) and conjugated with a galactose-grafted PEG chain, named LA-PegPI.
      We characterized the chemical structure and molecular weight of the copolymer and
      particle properties of LA-PegPI/pDNA. Furthermore, we showed that LA-PegPI/pDNA
      polyplexes possessed excellent stability in physiological salt solution, low
      cytotoxicity, and high transfection efficiency in the asialoglycoprotein receptor
      (ASGPR)-positive liver cells in vitro. Importantly, we also showed that through
      intraperitoneal injection of LA-PegPI/pDNA nanoparticles, the reporter gene was
      forcefully expressed in the liver hepatocytes of mice. Finally, we documented
      that intraperitoneal injection of LA-PegPI/pIL15 nanoparticles effectively
      suppressed tumor growth and prolonged survival time of tumor-bearing mice via
      activation of CD8+ T cells and NK cells and upregulation of the cytokines IFN
      gamma, TNF, and IL12 in an orthotopic hepatocellular carcinoma mouse model.
      Interestingly, LA-PegPI/pluc nanoparticles could effectively stimulate the
      proliferation of NK cells and inhibit tumor growth in this model. In summary, LA
      PegPI is a useful gene vector for immunogene therapy of hepatocellular carcinoma,
      and its potential for clinical application warrants further study.

PMID- 30195803
TI  - Ultra-high FRET efficiency NaGdF4: Tb3+-Rose Bengal biocompatible nanocomposite
      for X-ray excited photodynamic therapy application.
AB  - The limitation of light penetration depth invalidates the application of
      photodynamic therapy in deep-seated tumors. X-ray excited photodynamic therapy (X
      PDT), which is based on X-rays excited luminescent nanoparticles (XLNP), provides
      a new strategy for PDT in deep tissues. However, the high X-ray dosage used and
      non-specific cytotoxicity of the nanoparticle-photosensitizer nanocomposite (NPs
      PS) hamper in-vivo X-PDT applications. To address these problems, a simple and
      efficient NPs-PS nanocomposite using beta-NaGdF4: Tb3+ nanoparticles and widely
      used PS called Rose Bengal (RB) was designed. With perfectly matched spectrum of
      NPs emission and RB absorption upon X-ray excitation and covalent conjugation of
      a large amount of RB on NP surfaces to minimize the energy transfer distance, the
      system demonstrated ultra-high FRET efficiency up to 99.739%, which leads to
      maximum production of singlet oxygen for PDT with significantly increased anti
      tumor efficacy. By 2-aminoethylphosphonic acid surface modification of NPs,
      excellent biocompatibility was achieved even at a high concentration of 1 mg/mL.
      The in-vivo X-PDT efficacy was found around 90% of HepG2 tumor growth inhibition
      with X-ray dose of only 1.5 Gy, which shows the best anti-tumor efficacy at same
      X-ray dose level reported so far. The present work provides a promising platform
      for in-vivo X-PDT in deep tumors.

PMID- 30195804
TI  - Risk and survival of chronic myeloid leukemia after breast cancer: A population
      based study.
AB  - BACKGROUND: We aimed to investigate the risk and survival of chronic myeloid
      leukemia (CML) after breast cancer (BC) diagnosis. METHODS: We used the
      Surveillance, Epidemiology, and End Results 'SEER' database. Females, diagnosed
      with BC between 1992 and 2014, were selected and followed for the development of
      CML after a 6-month latency period from BC diagnosis. We used the Multiple
      Primary Standardized Incidence Ratios session of the SEER*Stat software (version
      8.3.4) to calculate the Observed/Expected (O/E) ratios with 95% confidence
      intervals (CI). To calculate the overall survival, we performed an unadjusted
      Kaplan-Meier analysis using the SPSS software. RESULTS: We included 474,866
      females with BC, of which 178 were later diagnosed with CML. We found the risk of
      CML to increase significantly after BC diagnosis (O/E = 1.26, 95% CI: 1.08-1.45)
      and the risk was specifically higher within the first 5 years of diagnosis (O/E =
      1.45, 95% CI: 1.16-1.8). When the risk was stratified by cancer stage, localized
      BC was associated with a significant increase in CML risk within 5 years of
      diagnosis (O/E = 1.4, 95% CI: 1.06-1.82), while regional BC was associated with a
      significant increase in CML risk after more than 5 years of diagnosis (O/E =
      1.59, 95% CI: 1.09-2.25). Moreover, radiotherapy, chemotherapy, and presence of
      hormonal receptors were associated with a significant increase in CML risk in BC
      patients. The median overall survival of CML after BC was 28 months. CONCLUSION:
      Breast cancer patients have an increased risk of developing CML and further
      investigation is required to establish the causes of this finding.

PMID- 30195805
TI  - Prevalence of bone pain decreases as lymph node stage increases in nonsmall cell
      lung cancer patients.
AB  - According to lung cancer guidelines, positron emission tomography scan is
      recommended for initial evaluation of bone metastasis. However, guidelines differ
      in their recommendations for when it should be used. We investigated the
      appropriate use of bone imaging in nonsmall cell lung cancer (NSCLC) patients.
      One hundred seventy-seven consecutive NSCLC patients who had distant metastases
      at presentation and were admitted between January 2012 and April 2016 were
      retrospectively reviewed. Among patients with bone metastases, we explored bone
      pain, number of bone metastases, location of bone metastases, and clinical tumor
      (T) and lymph node (N) classification. Sixty-three patients had bone metastases.
      There was a trend toward an increase in prevalence of bone metastases as lymph
      node stage increased. The prevalence of bone pain significantly decreased as N
      stage increased (p = 0.017). N0 and N2-3 patients were more likely to have
      multiple bone metastases (p = 0.038). Compared with patients who had a single
      bone metastasis, patients with multiple metastases had a significantly higher
      probability of having at least 1 bone metastasis located in the thorax or upper
      abdomen. All N0 patients have at least 1 bone metastasis in the thorax or upper
      abdomen. Clinical N0 NSCLC patients with bone metastasis are likely to have bone
      pain and have multiple bone metastases. N2-3 patients are more likely to have
      bone metastases but less likely to have bone pain. If NSCLC patients do not have
      bone pain, and CT of the chest and upper abdomen does not reveal any lymph node
      or bone metastasis, further survey for bone metastases may be omitted; bone
      imaging should be performed in N2 and N3 patients regardless of symptoms.

PMID- 30195807
TI  - Reply by Authors.

PMID- 30195806
TI  - Cardiovascular sequelae of breast cancer treatments: A review.

PMID- 30195808
TI  - Editorial Comment.

PMID- 30195809
TI  - Editorial Comment.

PMID- 30195810
TI  - Reply by Authors.

PMID- 30195812
TI  - Editorial Comment.

PMID- 30195813
TI  - Multidisciplinary treatment strategies in high-risk resectable melanoma: Role of
      adjuvant and neoadjuvant therapy.
AB  - Stage III melanoma encompasses a range of disease burdens, including microscopic
      foci of metastatic melanoma in a sentinel lymph node; bulky, clinically detected
      lymphadenopathy; and in-transit dermal metastases. After initial surgical
      management, patients with stage III melanoma at highest risk for recurrence are
      most likely to benefit from adjuvant therapy. Novel therapies that have improved
      the disease response rates and long-term survival of patients with advanced or
      metastatic melanoma have now been evaluated in the adjuvant setting, with the
      goal of eliminating residual microscopic disease to improve relapse-free and
      overall survival. Alternatively, implementing systemic therapies in the
      neoadjuvant setting for bulky, clinically detected disease can potentially limit
      surgical morbidity and improve understanding of an individual's response to
      applied therapy. With multiple therapeutic approaches currently under evaluation
      for adjuvant and neoadjuvant treatment of high-risk melanoma, establishing
      optimal treatment regimens, appropriate clinical endpoints, and treatment risk
      benefit profiles has become increasingly challenging. There is also a critical
      need to identify and validate biomarkers predictive of melanoma patient outcomes
      or treatment efficacy. This article provides an overview of current clinical
      evidence and ongoing trials of targeted therapy and immunotherapy in this rapidly
      evolving area of oncology.

PMID- 30195814
TI  - Diagnosis of early esophageal cancer using blue laser imaging (BLI).

PMID- 30195815
TI  - Management of ulcerative colitis in a real-life setting: An Italian multicenter,
      prospective, observational AIGO study.
AB  - BACKGROUND: No data are available on the variability in the clinical management
      of ulcerative colitis (UC) patients by Italian gastroenterologists. Therefore,
      improving the standards of UC care as provided by the National Welfare Clinical
      Path (PDTA), in accordance with the European Crohn's and Colitis Organization
      (ECCO) guidelines for UC, is not easy. AIMS: To assess the management of UC by
      Italian gastroenterologists in a real-life setting taking into account its
      variability. METHODS: This prospective, cross-sectional, observational study
      included IBD-specialized gastroenterologists (GSIBDs) and general
      gastroenterologists (GGs) working in Italian public hospital units. Consecutive
      patients with an UC flare were enrolled and the medical treatment evaluated. For
      each center, the physician in charge of the study (16 GSIBDs and 10 GGs) was
      administered two electronic questionnaires. RESULTS: Among 26 units, 573 UC
      patients were enrolled. Good adherence to the European guidelines was reported;
      GSIBDs reported greater adherence than GGs with a higher prescription of rectal
      and combination therapy in mild to moderate distal disease and a higher rate of
      hospitalization in severe UC. CONCLUSION: The management of UC by Italian
      gastroenterologists in clinical practice is good according to the ECCO consensus
      recommendations, though some discrepancies are present between GSIBDs and GGs.

PMID- 30195816
TI  - Allogeneic mesenchymal stromal cells for refractory luminal Crohn's disease: A
      phase I-II study.

PMID- 30195817
TI  - High fat diet modulates inflammatory parameters in the heart and liver during
      acute Trypanosoma cruzi infection.
AB  - The high fat diet (HFD) can trigger metabolic and cardiovascular diseases.
      Trypanosoma cruzi infection induces progressive inflammatory manifestations
      capable to affect the structure and the function of important organs such as the
      heart and liver. Here we aimed to investigate the effects of a HFD on the immune
      response and matrix metalloproteinase (MMP) activities during acute infection
      with the T. cruzi strain VL-10. The VL-10 strain has cardiac tropism and causes
      myocarditis in mice. Male C57BL/6 mice were treated with either: (i) regular diet
      (Reg) or (ii) HFD for 8 weeks, after which mice in each group were infected with
      T. cruzi. Mice were euthanized on day 30 after infection, and the liver and heart
      were subjected to histology and zymography to determine MMP-2 activities and
      plasma levels of IL-10, TNF, CCL2, and CCL5. T. cruzi-infected HFD animals had
      higher parasitemia, LDL and total cholesterol levels. Regardless of diet, plasma
      levels of all inflammatory mediators and cardiac MMP-2 activity were elevated in
      infected mice in contrast with the low plasma levels of leptin. HFD animals
      presented micro- and macrovesicular hepatic steatosis, while cardiac leukocyte
      infiltration was mainly detected in T. cruzi-infected mice. Our findings
      suggested that a HFD promotes higher circulating T. cruzi load and cardiac and
      liver immunopathogenesis in an experimental model using the VL-10 strain of the
      T. cruzi.

PMID- 30195818
TI  - Replacement of mycophenolate mofetil with a JAK inhibitor, AS2553627, in
      combination with low-dose tacrolimus, for renal allograft rejection in non-human
      primates.
AB  - In renal transplant patients, using mycophenolate mofetil (MMF) with calcineurin
      inhibitors (CNIs; cyclosporine and tacrolimus [TAC]) has led to a significant
      improvement in graft survival. However, reducing or withholding MMF due to its
      gastrointestinal adverse events increases rejection risk. CNI-sparing strategies
      are important to avoid CNI-related nephrotoxicity in clinical settings. Here, we
      investigated AS2553627, a JAK inhibitor replacing MMF in combination with a sub
      therapeutic dose of TAC to treat allograft rejection in a monkey model. AS2553627
      inhibited proliferation of IL-2 stimulated T cells with little species difference
      between monkeys and humans. In MMF monotherapy, oral administration of 20 or 40
      mg/kg/day prolonged graft survival with median survival times (MSTs) of 16.5 days
      and 33 days, respectively, whereas untreated animals showed MST of 6 days. In
      MMF/TAC (1 mg/kg/day, p.o.) combination therapy, pharmacokinetic analysis
      indicated that MMF 20 mg/kg/day achieved the clinical target AUC0-24h and
      prolonged renal allograft survival, with MST of 24 days. Oral administration of
      AS2553627 0.24 mg/kg/day in combination with TAC significantly prolonged renal
      allograft survival to MST of >90 days with low plasma creatinine levels.
      Histopathological analysis revealed that acute T cell-mediated rejection events
      such as vasculitis and interstitial mononuclear cell infiltration were
      significantly inhibited in AS2553627/TAC-treated allografts compared with MMF/TAC
      treated allografts. All AS2553627/TAC-treated monkeys surviving >90 days
      exhibited less interstitial fibrosis/tubular atrophy than monkeys in the MMF/TAC
      group. These results suggest that AS2553627 replacing MMF is an attractive CNI
      sparing strategy to prevent renal allograft rejection.

PMID- 30195819
TI  - Interleukin 33 ameliorates disturbance of regulatory T cells in pulmonary
      sarcoidosis.
AB  - The feature of pulmonary sarcoidosis is characterized by a Th1/Th17/regulatory T
      cells (Tregs) -driven inflammatory process in lung, resulting in noncaseating
      granulomas containing CD4+ T cells. Tregs increase in both lung and peripheral
      blood, with damaged immunoregulatory function. The current study investigated the
      effects of IL33 or anti-IL23 antibody on restoring the homeostasis and functions
      of Tregs in mycobacterial superoxide dismutase A (SodA)-induced pulmonary
      sarcoidosis. IL33 or anti-IL23 antibody was administered to mice with late-stage
      pulmonary sarcoidosis. The levels of Th1/Th17/Tregs and Tregs' suppressive
      functions were detected by fluorescence activated cell sorting (FACS) analysis or
      qPCR. The expressions of key proteins in PI3K/Akt/mTOR and TGF-beta/Smad2/Smad3
      signaling pathways were tested by western blot. IL33 administration was
      associated with the rebalance of Th1/Th2 and Tregs, as well as a superior
      suppressor activity of Tregs on effector T cells in sarcoidosis, probably through
      increasing ST2 expressions on Tregs, along with the suppression of PI3K/Akt/mTOR
      and TGF-beta/Smad2/Smad3 signaling pathways. Small dose of anti-IL23 antibody
      independently improved Th1/Th2 bias, but had limited effects on the homeostasis
      and ST2 expressions on Tregs. These results suggested a major anti-inflammatory
      ability of IL33 to ameliorate the disturbance of Th1/Th2 and Tregs in pulmonary
      sarcoidosis, and provided rationales for further strategies of targeting the
      IL33/ST2 signals in the treatment of pulmonary sarcoidosis.

PMID- 30195820
TI  - Disease Specific Ontology of Adverse Events: Ontology extension and adaptation
      for Chronic Kidney Disease.
AB  - BACKGROUND: Adverse Event (AE) ontology can be used to support interoperability
      and computer-assisted reasoning of AEs. Despite significant progress in
      developing biomedical ontologies, they are facing the obstacle of adoption partly
      because those ontologies are too general to meet the requirements of a specific
      domain. Understanding and representing of AEs for a specific domain such as
      Chronic Kidney Disease (CKD) has both theoretical and clinical significance. CKD
      patients are at a high risk for an array of disease-intervention specific AEs,
      and these in turn can contribute to disease progression unlike other diseases.
      This study proposes Disease Specific Ontology of Adverse Events (DSOAE) to
      address specific requirements of CKD, and applies it to different usage scenarios
      with real data. METHODS: We introduce a method for developing DSOAE through the
      extension and adaption of general ontologies by incorporating domain-specific
      information and usage requirements. It starts with specifying the goal and scope
      of a target domain (i.e. selecting seed ontologies), followed by identifying main
      AE classes and relations, extracting and creating classes and relations, aligning
      and identifying upper-level classes and lower-level classes, and finally
      populating the ontology with instances. Any of these steps may be repeated to
      refine the ontology. RESULTS: DSOAE contains 22 CKD-specific AE classes, which
      are grouped into two general categories: patient-reported AEs and
      biochemical/laboratory-related AEs. In addition, disease history and comorbidity
      classes as introduced in this study help model patient-related risk factors for
      AEs. With the support of DSOAE, we build a knowledge base of CKD-specific AEs
      using data from different sources (e.g. patient cohort data and social media),
      and apply the knowledge base to data analysis and data integration. CONCLUSIONS:
      DSOAE enables the interoperability of AEs across different sources and supports
      the development of a knowledge base of domain-specific AEs. DSOAE can also meet
      the needs of different usage scenarios. The approach to constructing DSOAE is
      generalizable and can be used to develop AE ontology in other domains.

PMID- 30195821
TI  - Motion analysis in the axial plane after realignment surgery for adolescent
      idiopathic scoliosis.
AB  - BACKGROUND: This study aimed to define changes occurring in axial plane motion
      after scoliosis surgery in patients with adolescent idiopathic scoliosis (AIS)
      using gait analysis. Pre- and postoperative axial plane motion was compared to
      healthy/control subjects. This may potentially improve our understanding of how
      motion is impacted by deformity and subsequent surgical realignment. METHODS: 15
      subjects with AIS underwent pre- and postoperative radiographic and gait
      analysis, with focus on axial plane motion (clockwise [CW] and counterclockwise
      [CCW]). Age, weight, and gender-matched controls (n = 13) were identified for
      gait analysis. Control, preoperative and postoperative groups were compared with
      paired student's t-tests. RESULTS: Surgical realignment resulted in significantly
      decreased in upper thoracic, thoracic, thoracolumbar and lumbar Cobb angles pre
      to-postoperatively (36.7 degrees  vs. 15.2 degrees , 60.1 degrees  vs. 25.6
      degrees , 47.7 degrees  vs. 17.7 degrees  and 27.2 degrees  vs. 4.8 degrees ,
      respectively) (all p < 0.05), with no significant change in thoracic kyphosis,
      lumbar lordosis, central sacral vertical line, pelvic incidence, and sagittal
      vertical axis. However, pelvic tilt significantly increased from 4.9 degrees  to
      8.1 degrees  (p = 0.035). Using gait analysis: preoperative thoracic axial
      rotation differed (mean CW and CCW rotation was 1.9 degrees  and 3.1 degrees  [p
      = 0.01]), whereas mean CW & CCW pelvic rotation remained symmetric (2.0 degrees 
      and 3.0 degrees ; p = 0.44). Postoperatively, CCW thoracic rotation range of
      motion decreased (CW: 0.6 degrees  and CCW: 1.4 degrees ; p = 0.31). No
      significant difference in postoperative pelvic rotation occurred (1.1 degrees 
      and 3.4 degrees ; p = 0.10). Compared to controls, AIS patients demonstrated no
      significant difference in total CW & CCW thoracic motion relative to the pelvis
      both pre- (14.9 degrees  and 12.3 degrees , respectively; p = 0.45) and
      postoperatively (12.9 degrees  and 12.3 degrees , respectively; p = 0.82).
      SIGNIFICANCE: AIS patients demonstrated abnormal gait patterns in the axial plane
      compared to normal controls. After surgical realignment and de-rotation, marked
      improvement in axial plane motion was observed, highlighting how motion analysis
      can afford surgeons three-dimensional perspective into the patient's functional
      status.

PMID- 30195822
TI  - Life is uncertain, eat dessert first: Uncertainty causes controlled and
      unemotional eaters to consume more sweets.
AB  - Sometimes even dieters with the best self-control overindulge. Uncertain
      situations may undermine the self-control of even well-controlled eaters. This
      study was designed to test the hypothesis that uncertainty increases unhealthy
      snacking. Participants were either told that they would be giving a speech, that
      they would be listening to a speech, or that they would find out later whether
      they were to give a speech or not. Among participants who typically reported good
      control over their eating or scored low on emotional eating, participants who
      were uncertain about whether they would be giving a speech ate more candy than
      participants who expected to not have to give a speech and even those who
      expected to have to give a speech. Participants who reported poor control over
      their eating or scored high on emotional eating did not eat significantly more
      when uncertain. These findings suggest that, for people who are typically able to
      control their eating, uncertainty increases snacking more than certainty of a
      negative outcome.

PMID- 30195824
TI  - The Application of Auriculotherapy to the Treatment of Chronic Spontaneous
      Urticarial: a SystematicReview and Meta-analysis.
AB  - Auriculotherapy has been extensively used for chronic spontaneous urticaria in
      China. However, the evidence of its effectiveness and safety for the treatment of
      chronic spontaneous urticaria is insufficient. Hence, we conducted this study to
      compare auriculotherapy or auriculotherapy joint treatment with western medicine
      for the cure of chronic spontaneous urticaria. This meta-analysis of seven RCTs
      showed that auriculotherapy or auriculotherapy joint treatment was significantly
      superior to western medicine in curing clinical signs and symptoms of chronic
      spontaneous urticaria (OR 2.61; 95% CI 1.54 to 4.43; p=0.0004), and also better
      in total effect rate (OR 3.81; 95% CI 2.07 to 7.01; p<0.0001). But,
      auriculotherapy or auriculotherapy joint treatment was similar to western
      medicine in improving clinical signs and symptoms of chronic spontaneous
      urticaria (OR 0.74; 95% CI 0.35 to 1.56; p=0.42). Auriculotherapy or
      auriculotherapy joint treatment was safer than western medicine for curing
      chronic spontaneous urticaria (OR 0.26; 95% CI 0.09 to 0.80; p=0.02).
      Auriculotherapy alone or auriculotherapy joint treatment appears to be more
      effective and safer than western medicine that contain antihistamines in the
      treatment of chronic spontaneous urticaria. However, these findings should be
      interpreted with caution due to the unclear risk bias of methodological quality
      and further studies with large-scale, better and more rigorously designed are
      necessary to prove these findings.

PMID- 30195823
TI  - The prevalence, awareness, and treatment of lipid abnormalities in Iranian adult:
      Surveillance of risk factors of noncommunicable diseases in Iran 2016.
AB  - BACKGROUND: Hypercholesterolemia is one of the modifiable risk factors for
      atherosclerosis and cardiovascular diseases. Prevention and treatment of
      hypercholesterolemia and other lipid abnormalities require reliable data
      regarding the current prevalence of these abnormalities in the country.
      OBJECTIVE: This study aims to determine the current prevalence, awareness, and
      treatment of lipid abnormalities in Iran. METHODS: We planned to recruit 31,050
      individuals who are 18 years old and above and take blood samples from
      individuals who are 25 years and above as representative sample at national and
      provincial levels in 2016. In practice, we recruited 21,293 Iranian adult aged
      more than 25 years through a systematic random sampling from 30 provinces of
      Iran. Sociodemographic, anthropometric, and lifestyle data and history of
      cardiometabolic diseases were gathered. Serum total cholesterol, high-density
      lipoprotein-cholesterol (HDL-C), triglyceride, low-density lipoprotein
      cholesterol (LDL-C), and non-HDL-C were investigated. The prevalence of lipid
      abnormalities, awareness, treatment, and achievement to non-HDL-C and LDL-C goals
      were determined based on National Cholesterol Education Program Adult Treatment
      Panel III criteria. RESULTS: In this representative Iranian adult population,
      80.0% had at least one lipid abnormality, 69.2% had low HDL-C, 39.5% had high non
      HDL-C, 28.0% had hypertriglyceridemia, and 26.7% hypercholesterolemia. Of those
      with hypercholesterolemia, 74.2% were aware of their lipid abnormality. Only
      22.0% and 36.5% of the study population met the desired level of non-HDL-C and
      LDL-C, respectively. CONCLUSION: Low HDL-C is the main lipid abnormality in adult
      Iranian population. The majority of the population did not meet the desired level
      of non-HDL-C and LDL-C. Public health preventive policies should be made and
      implemented to better manage dyslipidemia.

PMID- 30195825
TI  - Spread of activity following TMS is related to intrinsic resting connectivity to
      the salience network: A concurrent TMS-fMRI study.
AB  - Transcranial magnetic stimulation (TMS) modulates activity at local and regions
      distal to the site of simulation. TMS has also been found to modulate brain
      networks, and it has been hypothesized that functional connectivity may predict
      the neuronal changes at local and distal sites in response to a TMS pulse.
      However, a direct relationship between resting connectivity and change in TMS
      induced brain activation has yet to be demonstrated. Concurrent TMS-fMRI is a
      technique to directly measure this spread activity following TMS in real time. In
      twenty-two participants, resting-state fMRI scans were acquired, followed by four
      ten minute sessions of concurrent TMS-fMRI over the left dorsolateral prefrontal
      cortex (DLPFC). Seed-based functional connectivity to the individualized TMS
      target was examined using the baseline resting fMRI scan data, and the change of
      activity resulting from TMS was determined using a general linear model (High vs
      Low intensity TMS). While at the group level the spatial pattern of resting
      connectivity related to the pattern of TMS-induced cortical changes, there was
      substantial variability across individuals. This variability was further probed
      by examining individual's connectivity from the TMS target to six resting state
      networks. Only connectivity between the salience network (SN) and the TMS target
      site correlated with the RSC-TMS score. This suggests that resting state
      connectivity is correlated with TMS-induced changes in activity following DLPFC
      stimulation, particularly when the DLPFC target interacts with the SN. These
      results highlight the importance of examining such relationships at the
      individual level and may help to guide individual treatment in clinical
      populations.

PMID- 30195826
TI  - A Multisite Randomized Controlled Trial of a Patient-Centered Ventricular Assist
      Device Decision Aid (VADDA Trial).
AB  - BACKGROUND: Studies indicate that decision making and informed consent among
      patients considering left ventricular assist device (LVAD) support for advanced
      heart failure could be improved. In the VADDA (Ventricular Assist Device Decision
      Aid) trial, we tested a patient-centered decision aid (DA) to enhance the quality
      of decision making about LVAD therapy. METHODS: After an extensive user-centered
      design process, we conducted a multisite randomized trial of the DA compared with
      standard education (SE) among inpatients considering LVAD treatment for advanced
      heart failure The main outcome was LVAD knowledge at 1 week and 1 month after
      administration of the DA versus the SE, according to a validated scale. Secondary
      measures included prespecified quality decision making measures recommended by
      the International Patient Decision Aid Standards collaboration. RESULTS: Of 105
      eligible patients, 98 consented and were randomly assigned to the DA and SE arms.
      Patients receiving the VADDA exhibited significantly greater LVAD knowledge than
      the SE group at 1 week of follow-up (P = .01) but not at 1 month (P = .47). No
      differences were found between DA and SE patients in rates of acceptance versus
      decline of LVAD treatment (85% vs 78%; P = .74). Recipients in the DA arm
      reported greater satisfaction with life after implantation compared with
      nonrecipients (28 vs 23 out of 30; P = .008), although both arms reported high
      satisfaction. Patients rated the DA high in acceptability and usability.
      CONCLUSIONS: The VADDA enhances LVAD knowledge, particularly in the short term (1
      week) during the peak period of decision making. The DA does not encourage
      decision direction and reflects patient, caregiver, and physician preferences for
      content and format. CLINICAL TRIAL REGISTRATION:
      https://clinicaltrials.gov/ct2/show/NCT02248974. The trial is registered with
      clinicaltrials.gov (NCT02248974).

PMID- 30195827
TI  - Effects of Endurance Training on Detrimental Structural, Cellular, and Functional
      Alterations in Skeletal Muscles of Heart Failure With Preserved Ejection
      Fraction.
AB  - BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is underpinned
      by detrimental skeletal muscle alterations that contribute to disease severity,
      yet underlying mechanisms and therapeutic treatments remain poorly established.
      This study used a nonhuman animal model of HFpEF to better understand whether
      skeletal muscle abnormalities were (1) fiber-type specific and (2) reversible by
      various exercise training regimes. METHODS AND RESULTS: Lean control rats were
      compared with obese ZSF1 rats at 20 weeks and then 8 weeks after sedentary, high
      intensity interval training, or moderate continuous treadmill exercise. Oxidative
      soleus and glycolytic extensor digitorum longus (EDL) muscles were assessed for
      fiber size, capillarity, glycolytic metabolism, autophagy, and contractile
      function. HFpEF reduced fiber size and capillarity by 20%-50% (P < .05) in both
      soleus and EDL, but these effects were not reversed by endurance training. In
      contrast, both endurance training regimes in HFpEF attenuated the elevated
      lactate dehydrogenase activity observed in the soleus. Autophagy was down
      regulated in EDL and up-regulated in soleus (P < .05), with no influence of
      endurance training. HFpEF impaired contractile forces of both muscles by ~20% (P
      < .05), and these were not reversed by training. CONCLUSIONS: Obesity-related
      HFpEF was associated with detrimental structural, cellular, and functional
      alterations to both slow-oxidative and fast-glycolytic skeletal muscles that
      could not be reversed by endurance training.

PMID- 30195828
TI  - Right Ventricular Hypertrophy and Dilation in Patients With Human
      Immunodeficiency Virus in the Absence of Clinical or Echocardiographic Pulmonary
      Hypertension.
AB  - BACKGROUND: Involvement of right-sided heart chambers (RSHCs) in patients
      infected with human immunodeficiency virus (HIV) is common and is usually
      attributed to pulmonary arterial or venous hypertension (PH). However, myocardial
      involvement in patients with HIV is also common and might affect RSHCs even in
      the absence of overt PH. Our aim was to define morphologic and functional
      alterations in RSHC in patients with HIV and without PH. METHODS AND RESULTS: A
      total of 50 asymptomatic patients with HIV and 25 control subjects without
      clinical or echocardiographic signs for PH were included in the study.
      Transthoracic echocardiography was used to obtain measurements. Patients with HIV
      had significantly increased right ventricular end-diastolic diameter (RVEDD) and
      right ventricular free wall thickness (RVFWT), as well as increased right atrial
      area and pulmonary arterial diameter, compared with control subjects. After
      adjustment for age, sex, and body surface area, RVFWT (average 1.81 mm, 95%
      confidence interval [CI] 0.35-3.26 mm) and RVEDD (average 6.82 mm, 95% CI 2.40
      11.24 mm) were significantly higher in subjects infected with HIV. More patients
      with right ventricular hypertrophy were on antiretroviral treatment, and RVFWT
      was on average 1.3 mm higher (95% CI 0.24-2.37 mm) in patients on antiretroviral
      treatment after adjustment for confounders. CONCLUSIONS: These findings suggest
      that alterations in RSHCs were present in patients with HIV without PH.

PMID- 30195829
TI  - Concentration of Listeria monocytogenes in skim milk and soft cheese through
      microplate immunocapture.
AB  - Microplate immunocapture is an inexpensive method for the concentration of
      foodborne pathogens using an antibody-coated microplate. The objective of this
      study was to determine the efficacy of microplate immunocapture as an alternative
      to traditional enrichment for concentrating Listeria monocytogenes to levels
      detectable with selective plating or real-time PCR. L. monocytogenes isolates
      serologically characterized as Type 1 (1/2a) and Type 4 (untypeable) were grown
      overnight and diluted to 100 to 106 colony-forming units (CFU)/mL. The isolates
      were used to optimize microplate immunocapture in tryptic soy broth with 0.6%
      yeast extract (TSBYE), skim milk, and queso fresco samples. Following microplate
      immunocapture, the bacteria were streaked onto polymyxin-acriflavine-LiCl
      ceftazidime-aesculin-mannitol (PALCAM) agar, followed by incubation at 37 
      degrees C for 24 +/- 2 h. The bacteria also underwent real-time polymerase chain
      reaction (PCR). The optimized microplate immunocapture method was tested in
      triplicate for its ability to capture L. monocytogenes in broth and food samples.
      Overall recovery rates for L. monocytogenes in food samples at cell populations
      of 100, 102, and 104 CFU/25 g using microplate immunocapture with real-time PCR
      were 88.9%, 94.4%, and 100%, respectively. Recovery in these matrices using
      microplate immunocapture with selective plating was comparatively lower, at 0%,
      44.4%, and 100%, respectively. Conventional culture method showed 100% detection
      at each inoculation level. Microplate immunocapture combined with real-time PCR
      shows high potential to reduce the time required for detection, with
      concentration of L. monocytogenes to detectable levels within 1-4 h. The
      incorporation of a short enrichment step may improve recovery rates at low cell
      levels.

PMID- 30195830
TI  - Automated counting of bacterial colonies on agar plates based on images captured
      at near-infrared light.
AB  - Counting colonies is usually used in microbiological analysis to assess if
      samples meet microbiological criteria. Although manual counting remains gold
      standard, the process is subjective, tedious, and time-consuming. Some developed
      automatic counting methods could save labors and time, but their results are
      easily affected by uneven illumination and reflection of visible light. To offer
      a method which counts colonies automatically and is robust to light, we
      constructed a convenient and cost-effective system to obtain images of colonies
      at near-infrared light, and proposed an automatic method to detect and count
      colonies by processing images. The colonies cultured by using raw cows' milk were
      used as identification objects. The developed system mainly consisted of a
      visible/near-infrared camera and a circular near-infrared illuminator. The
      automatic method proposed to count colonies includes four steps, i.e.,
      eliminating noises outside agar plate, removing plate rim and wall, identifying
      and separating clustered or overlapped colonies, and counting colonies by using
      connected region labelling, distance transform, and watershed algorithms, etc. A
      user-friendly graphic user interface was also developed for the proposed method.
      The relative error and counting time of the automatic counting method were
      compared with those of manual counting. The results showed that the relative
      error of the automatic counting method was -7.4%~ + 8.3%, with average relative
      error of 0.2%, and the time used for counting colonies on each agar plate was 11
      21 s, which was 15-75% of the time used in manual counting, depending on the
      numbers of colonies on agar plates. The proposed system and automatic counting
      method demonstrate promising performance in terms of precision, and they are
      robust and efficient in terms of labor- and time-savings.

PMID- 30195831
TI  - Comprehensive effects of left ventricular assist device speed changes on alveolar
      gas exchange, sleep ventilatory pattern, and exercise performance.
AB  - BACKGROUND: Increasing left ventricular assist device (LVAD) pump speed according
      to the patient's activity is a fascinating hypothesis. This study analyzed the
      short-term effects of LVAD speed increase on cardiopulmonary exercise test (CPET)
      performance, muscle oxygenation (near-infrared spectroscopy), diffusion capacity
      of the lung for carbon monoxide (Dlco) and nitric oxide (Dlno), and sleep
      quality. METHODS: We analyzed CPET, Dlco and Dlno, and sleep in 33 patients
      supported with the Jarvik 2000 (Jarvik Heart Inc., New York, NY). After a maximal
      CPET (n = 28), patients underwent 2 maximal CPETs with LVAD speed randomly set at
      3 or increased from 3 to 5 during effort (n = 15). Then, at LVAD speed randomly
      set at 2 or 4, we performed (1) constant workload CPETs assessing O2 kinetics,
      cardiac output (CO), and muscle oxygenation (n = 15); (2) resting Dlco and Dlno
      (n = 18); and (3) nocturnal cardiorespiratory monitoring (n = 29). RESULTS: The
      progressive pump speed increase raised peak volume of oxygen consumption (12.5 +/
      2.5 ml/min/kg vs 11.7 +/- 2.8 ml/min/kg at speed 3; p = 0.001). During constant
      workload, from speed 2 to 4, CO increased (at rest: 3.18 +/- 0.76 liters/min vs
      3.69 +/- 0.75 liters/min, p = 0.015; during exercise: 5.91 +/- 1.31 liters/min vs
      6.69 +/- 0.99 liters/min, p = 0.014), and system efficiency (tau = 65.8 +/- 15.1
      seconds vs 49.9 +/- 14.8 seconds, p = 0.002) and muscle oxygenation improved. At
      speed 4, Dlco decreased, and obstructive apneas increased despite a significant
      apnea/hypopnea index and a reduction of central apneas. CONCLUSIONS: Short-term
      LVAD speed increase improves exercise performance, CO, O2 kinetics, and muscle
      oxygenation. However, it deteriorates lung diffusion and increases obstructive
      apneas, likely due to an increase of intrathoracic fluids. Self-adjusting LVAD
      speed is a fascinating but possibly unsafe option, probably requiring a
      monitoring of intrathoracic fluids.

PMID- 30195833
TI  - Utilization of injury care case studies: a systematic review of the World Health
      Organization's "Strengthening care for the injured: Success stories and lessons
      learned from around the world".
AB  - OBJECTIVE: Translation of evidence to practice is a public health priority.
      Worldwide, injury is a leading cause of morbidity and mortality. Case study
      publications are common and provide potentially reproducible examples of
      successful interventions in healthcare from the patient to systems level.
      However, data on how well case study publications are utilized are limited. To
      our knowledge, the World Health Organization (WHO) published the only collection
      of international case studies on injury care at the policy level. We aimed to
      determine the degree to which these injury care case studies have been translated
      to practice and to identify opportunities for enhancement of the evidence-to
      practice pathway for injury care case studies overall. METHODS: We conducted a
      systematic review across 19 databases by searching for the title, "Strengthening
      care for the injured: Success stories and lessons learned from around the world."
      Data synthesis included realist narrative methods and two authors independently
      reviewed articles for injury topics, reference details, and extent of
      utilization. FINDINGS: Forty-seven publications referenced the compilation of
      case studies, 20 of which included further descriptions of one or more of the
      specific cases and underwent narrative review. The most common category utilized
      was hospital-based care (15 publications), with the example of Thailand's quality
      improvement (QI) programme (10 publications) being the most commonly cited case.
      Also frequently cited were case studies on prehospital care (10 publications).
      There was infrequent utilization of case studies on rehabilitation (3
      publications) and trauma systems (2 publications). No reference described a case
      translated to a new scenario. CONCLUSIONS: The only available collection of
      policy-level injury care case studies has been utilized to a moderate extent
      however we found no evidence of case study translation to a new circumstance. QI
      programs seem especially amenable for knowledge-sharing through case studies.
      Prehospital care also showed promise. Greater emphasis on rehabilitation and
      health policy related to trauma systems is warranted. There is also a need for
      greater methodologic rigor in evaluation of the use of case study collections in
      general.

PMID- 30195832
TI  - Impact of body mass index on adverse events after implantation of left
      ventricular assist devices: An IMACS registry analysis.
AB  - BACKGROUND: Limited data exist describing impact of body mass index (BMI) on post
      left ventricular assist device (post-LVAD) outcomes. We sought to define the
      relationship between body mass index (BMI) and adverse events (AEs) after LVAD
      implantation by examining the ISHLT Mechanically Assisted Circulatory Support
      (IMACS) registry. METHODS: Patients implanted with a contemporary continuous flow
      (CF)-LVAD were stratified into 4 groups using pre-operative BMI: underweight (UW;
      BMI <=18.5 kg/m2); non-obese (NO; BMI >18.5 to <30 kg/m2); obese (OB; BMI >=30 to
      <40 kg/m2); and morbidly obese (MO; BMI >=40 kg/m2). Freedom from AEs was
      evaluated using the Kaplan-Meier method and risk factors for development of first
      AE were identified using multiphase parametric hazard modeling. AEs included
      infection, thromboembolic events, bleeding, device malfunction, and neurologic
      dysfunction. RESULTS: Between 2013 and 2015, a total of 9,408 patients underwent
      implantation of a CF-LVAD, which consisted of 368 (4%) UW, 5,719 (61%) NO, 2,770
      (29%) OB, and 444 (5%) MO patients. Survival among the 4 BMI cohorts was similar
      at 2years (70.8% to 75.8%, p = 0.24). MO patients were less likely to be free
      from a non-VAD-related infection (p < 0.0001) or device-related infection (p =
      0.0014) at 2years (50.3%, 70.7%) when compared with OB (58.3%, 78.7%), NO (65.2%,
      81.4%), and UW (68.9%, 77.4%) patients. UW (81.5%) and NO (81.3%) patients were
      more likely to be free from device malfunction at 2years when compared with OB
      (78.3%) and MO (72.6%) (p = 0.0006). Thromboembolic events were rare and more
      common in the UW cohort (p = 0.026). CONCLUSIONS: Although BMI was not correlated
      with 2-year mortality, an increased rate of infectious and device-related AEs was
      noted in OB and MO LVAD patients. In a group with few options for transplant, the
      event morbidity in obese patients can be expected to impact morbidity with longer
      support durations.

PMID- 30195834
TI  - Low Testosterone and Prostate Cancer: Is the Protection Real?

PMID- 30195835
TI  - Reply to Runqiang Yuan's Letter to the Editor re: James T. Kearns, Anna V. Faino,
      Lisa F. Newcomb, et al. Role of Surveillance Biopsy with No Cancer as a
      Prognostic Marker for Reclassification: Results from the Canary Prostate Active
      Surveillance Study. Eur Urol 2018;73:706-12.

PMID- 30195836
TI  - Racial disparities exist among burn patients despite insurance coverage.
AB  - BACKGROUND: Age, total burn surface area (TBSA), and inhalation injury are proven
      predictors of mortality and morbidity following burn injury. Most previous
      studies have also found that African Americans and females with burns also fare
      worse. We sought to determine whether these disparities were reduced when burn
      victims were analyzed separately by categories of insurance coverage. METHODS: We
      evaluated records in the National Burn Registry (NBR) from 2002 to 2011.
      Multivariate logistic regression was performed to determine factors associated
      with inpatient mortality, including age, TBSA, inhalation injury, race, and sex,
      and allowing for clustering by hospital. Separate models were constructed for
      each category of insurance. 95% confidence intervals (CI) not including 1 for any
      odds ratio were considered evidence of statistical significance (designated by *
      in the table below). RESULTS: NBR included records from 172,640 patients (55.8%
      Caucasian, 18.1% African American, 14.2% Hispanic, 6.4% other minority groups,
      5.4% unknown). Age, TBSA, and inhalation were strong predictors of mortality as
      expected. Non-African American males were the largest group for all insurance
      categories, and had the lowest mortality. Controlling for these factors, and
      compared with non-African American males, African American males had consistently
      increased odds of mortality regardless of insurance coverage. African American
      females had increased odds of mortality if they had Private, Medicare, or
      Medicaid insurance, and Non-African American females had increased odds of
      mortality if they had Private or Medicaid insurance. The association of Hispanic
      ethnicity with mortality was inconsistent or insignificant, and other minority
      groups had too few members to evaluate. Most patients were missing comorbidity
      data, and no other socioeconomic or hospital data were available in NBR.
      CONCLUSIONS: African American males with burn injury are at increased risk of
      mortality regardless of insurance coverage, and most females are at increased
      risk regardless of race. Analyzing the reasons for these disparities will require
      databases containing more complete comorbidity, socioeconomic, and/or hospital
      data.

PMID- 30195837
TI  - Newborn screening for congenital heart disease using echocardiography and follow
      up at high altitude in China.
AB  - BACKGROUND: Pulse oximetry screening for critical congenital heart disease (CHD)
      is inapplicable to high altitude due to the variedly decreased arterial
      saturations and rare complex CHD. We examined the incidence and spectrum of CHD
      in newborns using echocardiography at high altitude and followed up their
      outcomes. METHODS: A total of 1337 babies were studied. Echocardiography was
      performed in 1002 asymptomatic newborns (3-5 days). In the same period,
      retrospectively studied 394 newborns (<=2 days) admitted to the NICU where
      echocardiograph was performed in 335. In both groups, follow-up was made at 1-3,
      6 and 12-18 months. RESULTS: The incidence of CHD in asymptomatic newborns was
      27.8%, consisting secundum atrial septal defect (ASD) [175 (62.7%)], patent
      ductus arteriosus (PDA) [61 (21.9%)], ventricular septal defect (VSD) [8 (2.9%)]
      and multiple defects [35 (12.6%)]. And 19.4% in NICU patients with similar
      spectrum, except for 2 with complex CHD who died before discharge. By 12-18
      months of follow-up, 30% of CHD remained open. Thirteen patients developed mild
      to severe pulmonary arterial hypertension (PAH), and 2 of them died of heart
      failure. CONCLUSIONS: The incidence of CHD in newborns at high altitude is about
      20 times higher than that at low altitude, consisting mostly of simple forms with
      left to right shunt, with rare complex CHD. By 12-18 months, the incidence of CHD
      is still about 10 times higher than that at low altitude. About 8% patients
      developed PAH or death. Follow-up must be reinforced in order to provide early
      intervention and prevent from PAH or death.

PMID- 30195838
TI  - Borderline Q-waves in individuals without overt cardiovascular disease: Relations
      with adiposity, subclinical atherosclerosis and vascular stiffness.
AB  - BACKGROUND: Characteristics and risk factors associated with electrocardiographic
      borderline Q-waves are not fully elucidated, especially in individuals without
      overt cardiovascular disease (CVD). Also, the relation of isolated and non
      isolated borderline Q-waves with subclinical atherosclerosis and vascular
      stiffness is unknown. METHODS AND RESULTS: We included 5746 Netherlands
      Epidemiology of Obesity study participants without overt CVD. Participants were
      divided in three groups: no Q-waves (93.7%), isolated (4.6%) and non-isolated
      borderline Q-waves (1.7%). Borderline Q-waves were defined as Minnesota Codes
      1.2.x and 1.3.x and non-isolated as >=1 of abnormal QRS axis, left ventricular
      hypertrophy or ST/T abnormalities. Several characteristics and measures of body
      fat were assessed. Vascular stiffness was assessed by pulse wave velocity (PWV)
      and subclinical atherosclerosis by carotid intima-media thickness (cIMT).
      Percentage of men, alcohol intake, blood pressure and fasting glucose
      concentrations were, compared with no Q-waves, higher in the isolated and highest
      in the non-isolated borderline Q-wave group. Isolated borderline Q-waves were
      associated with higher body mass index (difference compared with no Q-waves: 1.0
      kg/m2; 95%CI: 0.3-1.7; p-value: 0.006), waist circumference (3.4 cm; 1.0-5.8;
      0.005), and visceral adipose tissue (21.9 cm2; 7.4-36.3; 0.003) and differences
      were even larger for non-isolated borderline Q-waves. Compared with no Q-waves,
      non-isolated borderline Q-waves were associated with higher PWV (1.2 m/s; 0.4
      2.0; 0.004) and cIMT (23.4 MUm; 3.0-43.8; 0.024), whereas isolated borderline Q
      waves were not. CONCLUSION: Cardiovascular risk factors and measures of body fat,
      especially abdominal adiposity, were higher in participants with isolated
      borderline Q-waves, compared with no Q-waves, and highest in the non-isolated
      borderline Q-wave group. Non-isolated borderline Q-waves were associated with
      subclinical atherosclerosis and vascular stiffness. Future studies should
      investigate potential added value of borderline Q-waves in CVD prediction.

PMID- 30195839
TI  - Contemporary ACHD training and the reality of the field in the United States.
AB  - BACKGROUND: Care delivery for the growing population of adults living with
      congenital heart disease (CHD) has been met with challenges due to a shortage of
      physicians trained to care for this population. To meet this urgent need,
      restructuring and standardization of the training programs were implemented in
      2015. The consequences of such a system on the graduating fellows have not been
      examined. METHODS: A 25-question electronic survey was distributed to early
      career physicians who graduated following training in adult CHD (ACHD) care
      between 2015 and 2017 and are currently practicing in the United States. The
      survey results were anonymous. RESULTS: Of the 30 physicians who trained in ACHD
      between 2015 and 2017 in the U.S., 21 (70%) responded to the survey. The majority
      completed a 2-year ACHD program, practice at an adult hospital, are happy with
      their current job, spend most of their time in ACHD-related activities, make on
      average around 250,000 USD for entry level positions, and prioritize supportive
      leadership and colleagues. Their training was adequate for their job
      requirements. However, the acquisition of an additional skill, in addition to
      clinical ACHD care, allowed them to secure a more ideal job. A sizeable number of
      jobs required program building or expansion with only 9.5% of trainees
      comfortable doing so immediately after graduation. CONCLUSIONS: The new ACHD
      training curriculum successfully meets most of the needs for ACHD jobs.
      Integration of specialty tracks, ensuring uniformity in the quality of training
      between programs, and promoting leadership skills may improve career prospects.

PMID- 30195840
TI  - Chronic thromboembolic pulmonary hypertension (CTEPH): Updated Recommendations
      from the Cologne Consensus Conference 2018.
AB  - Chronic thromboembolic pulmonary hypertension (CTEPH) is a subgroup of pulmonary
      hypertension that differs from all other forms of PH in terms of its
      pathophysiology, patient characteristics and treatment. For implementation of the
      European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension in
      Germany, the Cologne Consensus Conference 2016 was held and last updated in
      spring of 2018. One of the working groups was dedicated to CTEPH, practical and
      controversial issues were commented and updated. In every patient with suspected
      PH, CTEPH or chronic thromboembolic disease (CTED, i.e. symptomatic residual
      vasculopathy without pulmonary hypertension) should be excluded. Primary
      treatment is surgical pulmonary endarterectomy (PEA) in a multidisciplinary CTEPH
      centre. Inoperable patients or patients with persistent or recurrent CTEPH after
      PEA are candidates for targeted drug therapy. There is increasing experience with
      balloon pulmonary angioplasty (BPA) for inoperable patients; this option, like
      PEA, is reserved for specialised centres with expertise in this treatment method.

PMID- 30195841
TI  - Pulmonary hypertension in adults with congenital heart disease: Updated
      recommendations from the Cologne Consensus Conference 2018.
AB  - In the summer of 2016, delegates from the German Respiratory Society (DGP), the
      German Society of Cardiology (DGK) and the German Society of Pediatric Cardiology
      (DGPK) met in Cologne, Germany, to define consensus-based practice
      recommendations for the management of patients with pulmonary hypertension (PH).
      These recommendations were built on the 2015 European Pulmonary Hypertension
      guidelines, aiming at their practical implementation, considering country
      specific issues, and including new evidence, where available. To this end, a
      number of working groups was initiated, one of which was specifically dedicated
      to PH in adults associated with congenital heart disease (CHD). As such patients
      are often complex and require special attention, and the general PAH treatment
      algorithm in the ESC/ERS guidelines appears too unspecific for CHD, the working
      group proposes an analogous algorithm for the management of PH-CHD which takes
      the special features of this patient group into consideration, and includes
      general measures, supportive therapy, targeted PAH drug therapy as well as
      interventional and surgical procedures. The detailed results and recommendations
      of the working group on PH in adults with CHD, which were last updated in the
      spring of 2018, are summarized in this article.

PMID- 30195842
TI  - Multiple serial ECGs aid with the diagnosis and prognosis of Brugada syndrome.
AB  - BACKGROUND: A spontaneous coved-type ST segment elevation in the
      electrocardiogram (ECG) has long been recognized as a risk stratification tool in
      patients with Brugada syndrome (BrS). This Type-I ST segment elevation is known
      to exhibit high dynamicity, fluctuating between coved-type and non-coved ST
      segment elevation. Our objectives in this study were to: 1) Compare ECG
      parameters in patients with spontaneous coved-type (Type-I) vs. non-coved-type ST
      segment ECGs; 2) Determine the variability of these ECG parameters with repeated
      measurements; and 3) Assess the predictive value of ECG parameters in these two
      groups during follow-up. METHODS: Forty-two consecutive patients with BrS and
      implanted ICD were studied between 2000 and 2017. Serial ECGs and clinical
      characteristics were obtained over a period of 199 months. RESULTS: QT-interval,
      QTc-interval, QRS duration, Tp-e interval and Tp-e dispersion were all
      significantly longer in spontaneous Type I vs. non-Type 1 ECGs and all ECG
      parameters displayed significant variability during serial recording obtained
      throughout the follow-up period. Patients with a spontaneous Type I ECG during
      the 114 +/- 56 months follow-up period were at a much higher risk for VT/VF than
      those without a Type I ECG (p = 0.016). Moreover, the risk for development of
      life-threatening ventricular arrhythmias was directly related to the fraction of
      ECGs displaying a spontaneous Type I pattern during follow-up. CONCLUSION: Our
      study illustrates the need for multiple ECGs to aid with both the diagnosis and
      prognosis of BrS. Serial ECGs can assist with risk stratification based on the
      fraction of ECGs that display a spontaneous Type-I BrS ECG.

PMID- 30195844
TI  - Cusp catastrophe models for cognitive workload and fatigue in teams.
AB  - The use of two cusp catastrophe models has been effective for untangling the
      effects of cognitive workload, fatigue, and other complications on the
      performance of individuals. This study is the first to use the two models to
      separate workload and fatigue effects on team performance. In an experiment
      involving an emergency response simulation, 360 undergraduates were organized
      into 44 teams. Workload was varied by team size, number of opponents, and time
      pressure. The cusp models for workload and fatigue were more accurate for
      describing trends in team performance criteria compared to linear alternatives.
      Individual differences in elasticity-rigidity were less important than subjective
      workload and experimental conditions as control variables. Fluid intelligence
      within the team was an important compensatory ability in the fatigue model.
      Results further supported the nonlinear paradigm for the assessment of cognitive
      workload and fatigue and demonstrated its effectiveness for understanding team
      phenomena.

PMID- 30195843
TI  - Temporal changes within mechanical dyssynchrony and rotational mechanics in
      Takotsubo syndrome: A cardiovascular magnetic resonance imaging study.
AB  - BACKGROUND: The pathophysiological significance of dyssynchrony and rotation in
      Takotsubo syndrome (TTS) is unknown. We aimed to define the influence of
      cardiovascular magnetic resonance feature tracking (CMR-FT) dyssynchrony and
      rotational mechanics in acute and during clinical course of TTS. METHODS: This
      multicenter study included 152 TTS patients undergoing CMR (mean 3 days after
      symptom onset). Apical, midventricular and basal short axis views were analysed
      in a core-laboratory. Systolic torsion, diastolic recoil and dyssynchrony
      expressed as circumferential and radial uniformity ratio estimates (CURE and
      RURE: 0 to 1; 1 = perfect synchrony) were compared to a matched control group (n
      = 21). Follow-up CMR (n = 20 patients; mean 62 days, SD 7.2) and general follow
      up (n = 136; mean 3.3 years, SD 2.4) were performed. RESULTS: CURE was initially
      reduced compared to controls (p = 0.001) and recovered at follow-up (p < 0.001)
      as opposed to RURE (p = 0.116 and p = 0.179). CURE and RURE discriminated between
      ballooning patterns (p = 0.001 and p = 0.045). Recoil was generally impaired
      during the acute phase (p = 0.015), torsion only in highly dyssynchronous
      patients (p = 0.024). Diabetes (p = 0.007), physical triggers (p = 0.013) and
      malignancies (p = 0.001) predicted mortality. The latter showed a distinct
      association with impaired torsion (p = 0.042) and dyssynchrony (p = 0.047).
      Physical triggers and malignancies were related to biventricular impairment (p =
      0.004 and p = 0.026), showing higher dyssynchrony (p < 0.01), greater reduction
      of left ventricular function (p < 0.001) and a strong trend towards increased
      mortality (p = 0.074). CONCLUSION: Transient circumferential dyssynchrony and
      impaired rotational mechanics are distinct features of TTS with different
      severities according to the pattern of ballooning. Patients with malignancies and
      precipitating physical triggers frequently show biventricular affection, greater
      dyssynchrony and high mortality risk.

PMID- 30195845
TI  - A crossroads in predictive analytics monitoring for clinical medicine.
AB  - A new goal for medical informatics is to develop robust tools that integrate
      clinical data on a patient in order to estimate the risk of imminent adverse
      events. This new field of predictive analytics monitoring is growing very
      quickly. Its claims, however, can be vulnerable when clinicians fail to use the
      best mathematical and statistical tools, when quantitative scientists fail to
      grasp the nuances of clinical medicine, and when either fails to incorporate
      knowledge of physiology. Its potential, though is clear: we can provide more
      effective clinical decision support and make better predictive analytics
      monitoring tools if we apply principles learned from physiology and mathematics
      to the right problems in clinical medicine.

PMID- 30195846
TI  - Grade Groups Provides Improved Predictions of Pathologic and Early Oncologic
      Outcomes Compared with Gleason Score Risk Groups.
AB  - PURPOSE: The grade grouping (GG) system was introduced in 2013. Data from
      academic centers suggests GG better distinguishes between prostate cancer risk
      groups than the Gleason score (GS) risk groups. We compared the performance of
      both for predicting pathological/recurrence outcomes using data from Michigan
      Urological Surgery Improvement Collaborative (MUSIC). MATERIALS AND METHODS:
      Patients undergoing biopsy and radical prostatectomy (RP) within MUSIC (3/2012
      6/2017) were classified according to GG and GS. Outcomes included
      presence/absence of extraprostatic extension (EPE), seminal vesical invasion
      (SVI), positive lymph nodes (N1), positive surgical margins (PSM), and time to
      cancer recurrence (defined by having post-operative PSA>=0.2). Logistic and cox
      regression models were used to compare the difference in outcomes. RESULTS: 8052
      patients were identified. Controlling for patient characteristics, significantly
      higher risks of EPE, SVI, and N1 were observed for biopsy GG3 vs. GG2, and for
      GG5 vs. GG4 (p<0.001). Biopsy GG3, GG4, and GG5 also had shorter time to
      biochemical recurrence (BCR) when compared to GG2, GG3, and GG4, respectively
      (p<0.001). GG3, GG4, and GG5 at RP were each associated with greater probability
      of recurrence compared to the next lower GG (p<0.001). GG (vs. GS) had better
      predictive power for EPE, SVI , N1, and BCR. CONCLUSIONS: GG at biopsy and RP
      allows for better discrimination of recurrence-free survival between individual
      risk groups than GS risk groups with GG2, GG3, GG4, and GG5 each incrementally
      associated with increased risk.

PMID- 30195847
TI  - Ureteral Complications of Pediatric Renal Transplantation.
AB  - PURPOSE: Ureteral complications following renal transplantation are more common
      in children than in adults. We identify potential risk factors for ureteral
      complications in pediatric patients. MATERIALS AND METHODS: We performed a
      retrospective cohort study of patients who underwent renal transplantation at
      Lurie Children's Hospital between 2004 and 2016. The associations between patient
      characteristics, operative factors, graft characteristics and post-operative
      complications were analyzed. RESULTS: and Limitations: 224 renal transplantations
      in 219 patients were identified. Pre-existing bladder pathology was present in
      25% of cases. The overall rate of ureteral complications was 16%, with
      symptomatic vesicoureteral reflux being the most common. Ureteral complications
      were significantly more common in patients with underlying bladder pathology (26%
      vs. 12%, p=0.01). The rate of post-operative vesicoureteral reflux in patients
      with bladder pathology was lower when a urologist performed the reimplantation,
      but this was not statistically significant (15% vs. 27%, p=0.35). Urologists were
      significantly more likely to perform the ureteral anastomosis in patients on
      clean intermittent catheterization (85% vs. 43%, p=0.004) and in patients with a
      history of complex bladder reconstruction (75% vs. 28%, p<0.001). CONCLUSIONS:
      Patients with existing bladder pathology are at a higher risk for ureteral
      complications, particularly vesicoureteral reflux. As pediatric urologists
      routinely perform ureteral reimplantation in patients with existing bladder
      pathology, these patients may benefit from a multidisciplinary approach between
      urology and transplant surgery at the time of renal transplantation.

PMID- 30195848
TI  - Bone density changes following surgical correction of femoroacetabular
      impingement deformities.
AB  - OBJECTIVE: Femoroacetabular impingement (FAI) involves abnormal hip biomechanics
      due to deformities and is associated with osteoarthritis. Bone mineral density
      (BMD) in the acetabulum is higher in subjects with convex femoral (cam) FAI
      deformities compared to control subjects. The objective of this study was to
      assess post-operative changes of BMD with and without surgical correction of the
      cam deformity. DESIGN: Thirteen patients with bilateral cam deformities but
      unilateral symptoms underwent pre-operative and follow-up computed tomography
      (CT) scans of both hips. The deformity was surgically removed from the
      symptomatic hip. BMD was measured in regions of interest (ROI) around the
      superior acetabulum from CT scans at both time points. The contralateral
      untreated hip was used as a within-patient control. Changes in BMD were assessed
      by two-way repeated measures ANOVA (side, time) and paired t-tests. RESULTS: A
      greater BMD decrease was seen in the treated compared to the untreated hip (P <
      0.0018). BMD within the superior acetabulum decreased by 39 mg/cc on the treated
      side (P < 0.0001) but only 9 mg/cc (P = 0.15) in the untreated contralateral hip.
      These changes represent 7.1% and 1.7% of the pre-operative BMD on the respective
      sides. CONCLUSIONS: BMD decreased in the treated hip, suggesting a positive
      effect of surgical correction in relieving stresses within the hip joint. Longer
      term follow-up is required to assess the ultimate fate of the articular cartilage
      within the joint. This study showed that surgical correction of the cam deformity
      in patients with FAI may alter the pathological biomechanics within the joint.

PMID- 30195849
TI  - The mechanics of agonistic muscles.
AB  - INTRODUCTION: In this study, we tested two assumptions that have been made in
      experimental studies on muscle mechanics: (i) that the torque-angle properties
      are similar among agonistic muscles crossing a joint, and (ii) that the sum of
      the torque capacity of individual muscles adds up to the torque capacity of the
      agonist group. METHODS: Maximum isometric torque measurements were made using a
      specifically designed animal knee extension dynamometer for the intact rabbit
      quadriceps muscles (n = 10) for knee angles between 60 and 120 degrees . The
      nerve branches of the vastus lateralis (VL), vastus medialis (VM) and rectus
      femoris (RF) muscles were carefully dissected, and a custom made nerve cuff
      electrode was implanted on each branch. Knee extensor torques were measured for
      four maximal activation conditions at each knee angle: VL activation, VM
      activation, RF activation, and activation of all three muscles together. RESULTS:
      With the exception of VL, the torque-angle relationships of the individual
      muscles did not have the shape of the torque-angle relationship obtained when all
      muscles were activated simultaneously. Furthermore, the maximum torque capacity
      obtained by adding the individual torque capacities of VL, VM and RF was
      approximately 20% higher than the torques produced when the three muscles were
      activated simultaneously. DISCUSSION: These results bring into question our
      understanding of in-vivo muscle contraction and challenge assumptions that are
      sometimes made in human and animal muscle force analyses.

PMID- 30195850
TI  - Effect of chronic idiopathic low back pain on the kinetic gait characteristics in
      different foot masks.
AB  - Identification of kinetic variables in different masks of foot is important for
      the evaluation and treatment of chronic low back pain. The aim of this study was
      to investigate the effect of chronic idiopathic low back pain on kinetic
      variables of gait in different foot masks. 11 idiopathic chronic low back pain
      patients and 13 healthy matched controls participated in this study. Using Emed
      foot-scanner system, the ground reaction force and impulse were measured during
      barefoot normal walking. Then, the average footprints were divided into 10 masks
      using the Automask program and the data were extracted using Multimask Evaluation
      programs. The low back pain disability was measured by Quebec questionnaire. Our
      results revealed that the ground reaction force and impulse in medial and lateral
      midfoot and hallux masks of patients were significantly lower than controls.
      Furthermore, these patients demonstrated greater ground reaction force and
      impulse in 3-5th metatarsals mask than control group. There was a significant
      interaction between the low back pain and the foot masks factors. In conclusion,
      the ground reaction forces and impulses in different areas of foot are affected
      by low back pain. Therefore, the kinetic gait analysis should be considered as an
      appropriate tool in evaluation and prescribing proper treatment program in low
      back pain patients.

PMID- 30195851
TI  - Estimation of vertical walking ground reaction force in real-life environments
      using single IMU sensor.
AB  - Monitoring natural human gait in real-life environments is essential in many
      applications, including quantification of disease progression, monitoring the
      effects of treatment, and monitoring alteration of performance biomarkers in
      professional sports. Walking ground reaction forces are among the key parameters
      necessary for gait analysis. However, these parameters are commonly measured
      using force plates or instrumented treadmills which are expensive and bulky and
      can only be used in a controlled laboratory environment. Despite the importance
      of real-life gait measurement, developing reliable and practical techniques and
      technologies necessary for continuous real-life monitoring of gait is still an
      open challenge, mainly due to the lack of a practical and cost-effective wearable
      technology for ground reaction force measurement. This paper presents a
      methodology to estimate the total walking ground reaction force GRFvt in the
      vertical direction using data from a single inertial measurement unit.
      Correlation analysis of the vertical acceleration of different body segments with
      GRFvt indicated that the 7th cervical vertebrae is one of the best locations for
      the sensor. The proposed method improves the accuracy of the state-of-the-art
      GRFvt estimation by 25%, by utilising the time-varying ratio of the vertical
      acceleration of the human body centre of mass and measured C7 vertical
      acceleration. Results of this study showed that the proposed method estimated
      consistently the GRFvt in both indoor and urban outdoor environment, with a 4-8%
      peak-to-peak normalised root mean square error.

PMID- 30195852
TI  - The effect of football helmet facemasks on impact behavior during linear drop
      tests.
AB  - Football helmet certification tests are performed without a facemask attached to
      the helmet; however, the facemask is expected to contribute substantially to the
      structure and dynamics of the helmet through the effects of added mass and added
      stiffness. Facemasks may increase the peak acceleration and severity index;
      therefore, as-used helmets may not mitigate head impacts as effectively as
      certification tests indicate. Furthermore, the effect is expected to depend on
      the helmet design as well as the orientation and speed of the impact. This study
      examined the influence of the facemask on impact behavior in a NOCSAE-style
      linear drop test and the interactions with location, velocity, and helmet model.
      Increases in peak acceleration and severity index of up to 36% were observed when
      helmets were tested with the facemask.

PMID- 30195853
TI  - Identification of regional/layer differences in failure properties and thickness
      as important biomechanical factors responsible for the initiation of aortic
      dissections.
AB  - Thoracic aortic dissections involving the ascending aorta represent one of the
      most dramatic and lethal emergencies in cardiovascular surgery. It is therefore
      critical to identify the mechanisms driving them and biomechanical analyses hold
      great clinical promise, since rupture/dissection occur when aortic wall strength
      is unable to withstand hemodynamic stresses. Although several studies have been
      done on the biomechanical properties of thoracic aortic aneurysms, few data are
      available about thoracic aortic dissections. Detailed mechanical tests with
      measurement of tissue thickness and failure properties were performed with a
      tensile-testing device on 445 standardized specimens, corresponding to 19
      measurement sites per inner (intima with most of media)/outer layer (leftover
      media with adventitia); harvested from twelve patients undergoing emergent
      surgical repair for type A dissection. Our data suggested inherent differences in
      tissue properties between the origin of dissection and distal locations, i.e.
      thinner and stiffer inner layers that might render them more vulnerable to
      tearing despite their increased strength. The strength of tissue
      circumferentially was greater than that longitudinally, likely determining the
      direction of tear. The relative strengths of the inner: ~{65,40}N/cm2 and outer
      layer: ~{350,270}N/cm2 in the two principal directions of dissected tissue were
      differentiated from the intima: ~{100,75}N/cm2, media: ~{150,55}N/cm2, and
      adventitia: ~{270,190}N/cm2 of non-dissected ascending aortic aneurysms (Sokolis
      et al., 2012), in favor of weaker inner and stronger outer layers, allowing an
      explanation as to why the presently-studied tissue suffered dissection, i.e. tear
      of the inner layers, and not rupture, i.e. full tearing across the entire wall
      thickness.

PMID- 30195854
TI  - Age of alcohol use initiation and psychiatric symptoms among young adult trauma
      survivors.
AB  - Alcohol use disorder (AUD) evidences high rates of comorbidity with a range of
      psychiatric disorders, particularly within high-risk populations, such as
      individuals exposed to physical or sexual violence. Increasing efforts are
      focused on understanding the role of early alcohol use (e.g., during adolescence)
      on emotional and psychiatric functioning over time, as well as sex differences in
      these associations. The aim of the current study was to evaluate patterns of
      association between age of initiation of regular alcohol use and posttraumatic
      stress disorder (PTSD), anxiety, and depressive symptoms as a function of sex.
      Participants were 269 college students with a history of interpersonal trauma and
      alcohol use who completed a battery of questionnaires regarding alcohol use and
      emotional health. Neither bivariate correlations nor results from structural
      equation models covarying for key factors showed a relationship between age of
      alcohol use initiation and current psychiatric symptoms among men (n = 63).
      Results of a structural equation model supported an association between earlier
      age of alcohol use initiation and greater levels of current PTSD (beta = -0.14),
      anxiety (beta = -0.15), and depression symptoms (beta = -0.16) in the female sub
      sample (n = 202), after controlling for covariates, as well as intercorrelations
      among criterion variables. Statistical support for sex as a moderator of these
      associations was not detected. The current study provides preliminary evidence
      for potential sex differences in the role of early alcohol use in the development
      of psychiatric symptoms and highlights the need for systematic longitudinal
      research.

PMID- 30195855
TI  - Electroencephalographic time-frequency patterns of braking and acceleration
      movement preparation in car driving simulation.
AB  - The objective of the present work was to identify electroencephalographic (EEG)
      components in order to distinguish between braking and accelerating intention in
      simulated car driving. To do so, we collected high-density EEG data from thirty
      participants while they were driving in a car simulator. The EEG was separated
      into independent components that were clustered across participants according to
      their scalp map topographies. For each component, time-frequency activity related
      to braking and acceleration events was determined through wavelet analysis, and
      the cortical generators were estimated through minimum norm source localisation.
      Comparisons of the time-frequency patterns of power and phase activations
      revealed that theta power synchronisation distinguishes braking from acceleration
      events 800 ms before the action and that phase-locked activity increases for
      braking 800 ms before foot movement in the theta-alpha frequency range. In
      addition, source reconstruction showed that the dorso-mesial part of the premotor
      cortex plays a key role in preparation of foot movement. Overall, the results
      illustrate that dorso-mesial premotor areas are involved in movement preparation
      while driving, and that low-frequency EEG rhythms could be exploited to predict
      drivers' intention to brake or accelerate.

PMID- 30195856
TI  - Impact of benzimidazole and dithiocarbamate fungicides on the photosynthetic
      machinery, sugar content and various antioxidative enzymes in chickpea.
AB  - BACKGROUND AND AIMS: Fungicides, though beneficial for agricultural productivity,
      are known to interfere with the basic metabolism and induce the formation of
      various biomolecules and also alter the physiological parameters of plant growth.
      The present study is an attempt to understand the effect of different conc. of
      benzimidazole (Carbendazim) and dithocarbamate (Mancozeb) fungicides on
      photosynthetic components such as chlorophyll content, total sugar and phenolic
      content and various antioxidative enzymes in developing seedlings of chickpea.
      MATERIAL AND METHODS: Chickpea seeds of two cultivars (PDG-4 and GPF-2) were
      incubated with different conc. (0.1, 0.25 and 0.5%) of the fungicide for 24 and
      48 h and then allowed to germinate for 10 days in an incubated chamber. Seedlings
      were analyzed for various physiological parameters such as variation in
      root/shoot length, photosynthetic activity (chlorophyll content), total sugar and
      phenolic content and activity of antioxidative enzymes such as GPX, CAT and SOD
      etc. RESULTS AND CONCLUSIONS: Compared to the unstressed samples, fungicide
      stress resulted in an overall decrease in root/shoot length, relative water
      content etc. thus indicating that the applied fungicides adversely affects the
      rate of germination of seedlings. A differential behaviour of various chlorophyll
      (Chla, Chlb, total chlorophyll) contents suggests that fungicides stress affects
      the photosynthetic machinery. Estimations of sugar and total phenolic content
      indicated that higher conc. of the fungicide lowered the total sugar content at
      the 10-day-old seedling stage; thereby giving an indication that the fungicide
      may interferes with carbohydrate metabolism. We observed that the level of
      peroxidase increased at higher conc. of the both types of fungicide as compared
      to control samples whereas the catalase activity increased in PDG 4 but a lower
      activity was observed in GPF-2 under increasing conc. of both the fungicides. The
      levels of superoxide dismutase decreased in PDG-4 but increased in GPF-2 under
      higher conc. of both the fungicides thus indicating that different varieties of
      chickpea behaved differently and triggers various antioxidant enzymes as defence
      mechanism to counter the fungicides stress.

PMID- 30195857
TI  - Enzyme-assisted extraction and liquid chromatography-inductively coupled plasma
      mass spectrometry for the determination of arsenic species in fish.
AB  - A sensitive, simple and rapid method for the simultaneous determination of eleven
      arsenic species has been developed. A high performance liquid chromatography
      inductively coupled plasma mass spectrometry (HPLC-ICP-MS) technique was used for
      the analysis of eleven arsenic species in less than 17 min. Different extraction
      solutions were explored and the recovery results using water and aqueous acidic
      solvents, aqueous organic solvents and enzymes showed that 40 mg protease with
      0.75 mL 0.5% hydrochloric acid (v/v) as the extraction agent gave the best
      experimental results. Species separation with ammonium carbonate solution as the
      mobile phase was conducted on an anion-exchange chromatographic column using
      gradient elution. The column temperature was 20  degrees C and kinetic energy
      discrimination (KED) was employed to eliminate spectral interference. The use of
      KED mode effectively removed interference from 75ArCl. The detection limit (LD)
      of the method was in the range of 0.11-0.59 MUg kg-1. Repeatability values
      obtained for spiked real fish samples were in the range of 1.1%-7.6%. Accuracy
      was calculated based on the analysis of spiked real fish samples at five
      concentration levels. Obtained recoveries were 91%-106%. The validated method was
      used in a pilot study to analyze real samples of fish, the organic arsenic
      especially AsB was the major arsenic specie present in the analyzed samples, only
      trace amount of inorganic arsenic were detected. The analytical method should
      improve the assessment of human exposure associated with arsenic intake from
      fish.

PMID- 30195858
TI  - Application of steric exclusion chromatography on monoliths for separation and
      purification of RNA molecules.
AB  - Steric exclusion chromatography (SXC) is a method for separation of large target
      solutes based on their association with a hydrophilic stationary phase through
      mutual steric exclusion of polyethylene glycol (PEG). Selectivity in SXC is
      determined by the size or shape (or both) of the solutes alongside the size and
      concentration of PEG molecules. Elution is achieved by decreasing the PEG
      concentration. In this study, SXC applicability for the separation and
      purification of single-stranded (ss) and double-stranded (ds) RNA molecules was
      evaluated for the first time. The retention of ssRNA and dsRNA molecules of
      different lengths on convective interaction media (CIM) monolithic columns was
      systematically studied under variable PEG-6000 and NaCl concentrations. We
      determined that over 90% of long ssRNAs (700-6374 nucleotides) and long dsRNAs
      (500-6374 base pairs) are retained on the stationary phase in 15% PEG-6000 and
      >=0.4 M NaCl. dsDNA and dsRNA molecules of the same length were partially
      separated by SXC. Separation of RNA molecules below 100 nucleotides from longer
      RNA species is easily achieved by SXC. Furthermore, SXC has the potential to
      separate dsRNAs from ssRNAs of the same length. We also demonstrated that SXC is
      suitable for the enrichment of ssRNA (PRR1 bacteriophage) and dsRNA (Phi6
      bacteriophage) viral genomes from contaminating cellular RNA species. In summary,
      SXC on CIM monolithic columns is an appropriate tool for rapid RNA separation and
      concentration.

PMID- 30195859
TI  - Gradient extractive phase prepared by controlled rate infusion method: An
      applicable approach in solid phase microextraction for non-targeted analysis.
AB  - The aim of this study is to introduce an extractive phase based on gradient
      concept by continuous changing in chemical functional groups for non-targeted
      analysis. For this purpose, three different two-component coatings containing (3
      aminopropyl)trimethoxysilane (APTES) as polar and either phenyltriethoxysilane
      (PTES), octyl-trimethoxysilane (OTMS) or methyltrimethoxysilane (MTMS) as
      nonpolar precursors were formed on the modified stainless steel wires using
      controlled rate infusion (CRI) method. The presence of polar and/or non-polar
      functional groups on the surface of substrate was evaluated by Fourier-transform
      infrared spectroscopy (FTIR) together with contact angles determined alongside
      the gradient surface. The morphology and thickness of the prepared fibers were
      also investigated by scanning electron microscopy (SEM). Furthermore, uniform
      single-component fibers from polar (APTES) and nonpolar (PTES) coatings were
      fabricated in order to be compared with the gradient sorbent. The gradient phase
      was implemented as a fiber coating in headspace- or immersed-solid phase
      microextraction of various compounds including chlorobenzenes, polycyclic
      aromatic hydrocarbons, chlorophenols and volatile organic compounds (Log Kow
      range: -0.77 to 4.64). Under the optimized condition, the limits of detection and
      quantification were obtained in the range of 0.01-0.5 MUg L-1 and 0.05-1.5 MUg L
      1, respectively. The intra-day and inter-day relative standard deviations of 2
      10% and 11-17% were achieved, respectively. The method was successfully applied
      to the extraction of VOCs from real water sample and relative recoveries were
      between 89 and 105%. The capability and efficiency of the gradient coating
      appears to be quite appropriate for non-targeted analysis.

PMID- 30195861
TI  - Adaptive non-negative projective semi-supervised learning for inductive
      classification.
AB  - We discuss the inductive classification problem by proposing a joint framework
      termed Adaptive Non-negative Projective Semi-Supervised Learning (ANP-SSL).
      Specifically, ANP-SSL integrates the adaptive inductive label propagation,
      adaptive reconstruction weights learning and the neighborhood preserving
      projective nonnegative matrix factorization (PNMF) explicitly. To make the label
      prediction results more accurate, ANP-SSL incorporates the semi-supervised data
      representation and classification errors into regular PNMF for minimization,
      which can enable our ANP-SSL to perform the adaptive weights learning and label
      propagation over the spatially local and part-based data representations, which
      differs from most existing work that usually assign weights and predict labels
      based on the original data that often has noise and corruptions. Moreover,
      existing methods usually pre-assign weights before the process of label
      estimation, but such operation cannot ensure the learnt weights by independent
      step to be optimal for the subsequent classification. The combined representation
      error can also make the learnt reduced part-based representations of neighborhood
      preserving PNMF, which can potentially enhance the prediction results. By
      minimizing the classification error jointly over the neighborhood preserving
      nonnegative representation can make the embedding based classification efficient.
      Extensive results on several public image databases verified the effectiveness of
      our ANP-SSL, compared with other state-of-the-art methods.

PMID- 30195860
TI  - Micro-fabricated packed metal gas preconcentrator for enhanced monitoring of
      ultralow concentration of isoprene.
AB  - A novel non-silicon-based micro-preconcentration device, as a pretreatment
      component in a portable gas chromatography system, was developed for the
      preconcentration one of the trace volatile organic compounds (VOCs) in the
      exhaled gases, which is one typical biomarker for the chronic liver disease
      (CLD). The device was designed as an array of manifold-shaped rectangular metal
      micro-channels with flat dimensions of 16 mm * 12.6 mm and the internal empty
      volume is 14.4 MUL on the copper substrate. Instead of the non-silicon
      fabrication process, the traditional laser etching technology (LET) was optimized
      to etch micro-channels, and vacuum diffusion welding (VDW) was applied to form
      internal channels. The fabricated chip was filled with Carbopack X adsorbent. In
      the testing, the metal gas preconcentrator (MGP) was installed in a commercial GC
      (gas chromatography) and nitrogen was used as carrier gas and desorbed gas. With
      the MPG, up to 352 of concentration factor can be achieved for 10 ppb isoprene.
      The developed MGP, which has advantages of high strength, low cost, good thermal
      conductivities, can potentially be used for non-invasive screening of advanced
      liver fibrosis by monitoring isoprene concentrations in exhaled breath.

PMID- 30195862
TI  - Novel Use of a Nurse-Led Telemedicine Team in Acute Stroke: A Retrospective
      Review of the Impact on a Regional Health Care System.
AB  - INTRODUCTION: Despite the increasing incidence of acute ischemic stroke in the
      United States, many health care facilities remain unprepared to manage patients
      with acute stroke, including the administration of intravenous alteplase
      (recombinant tissue plasminogen activator [rTPA]). This has led to an opportunity
      for telemedicine systems to facilitate these evaluations and acute medical stroke
      treatment decisions. However, even telemedicine systems can fail to provide
      timely evaluation and management of the patient with acute stroke. The purpose of
      this retrospective study was to compare stroke outcome metrics pre- and
      postimplementation of a hybrid, local nurse-led "stroke-responder" telemedicine
      system. METHODS: A retrospective chart review was performed on 21 patients at a
      regional community hospital between the years of 2014 and 2016. Data were
      collected pre- and postimplementation of a local stroke-responder system.
      Outcomes obtained included door-to-alert time, door-to-computerized tomography
      (CT) time, door-to-rtPA order time, and door-to-rtPA bolus dose administration
      time. Outcomes were compared among years. RESULTS: Between 2014 and 2016, 21
      charts were reviewed. Decreased mean times were observed for all metrics. The
      mean time for door-to-alert decreased from 21.19 to 5.84 minutes (P = 0.021),
      door-to-CT from 29.9 to 12.2 minutes (P = 0.022), door-to-rtPA order 88.4 to 53
      minutes (P = 0.021), and door-to-rtPA administration from 106.94 to 64.65 minutes
      (P = 0.001). CONCLUSION: In an acute stroke telemedicine system, implementation
      of a local nurse-led "stroke responder" system resulted in significantly
      decreased acute stroke metrics for a community hospital within a regional
      hospital system.

PMID- 30195863
TI  - Sepsis Screening in Triage to Decrease Door-to-Antibiotic Time.
AB  - INTRODUCTION: Identifying patients with sepsis at triage can lead to a decrease
      in door-to-antibiotic time. Our community hospital emergency department's mean
      door-to-antibiotic time was 105.3 minutes, falling short of the Surviving Sepsis
      Campaign guideline's benchmark goal of 60 minutes. One of the most common reasons
      for treatment delays was that patients with sepsis were not identified upon
      entrance to the emergency department. A solution to the delay was to implement a
      practice improvement project by having the triage nurse screen all patients for
      sepsis upon entrance to the emergency department. METHODS: A sepsis-screening
      tool was used to identify patients with sepsis and was based on systemic
      inflammatory response syndrome (SIRS) criteria. Patients screening positive were
      prioritized for ED bed space. The change in process allowed more rapid ED
      physician evaluation and antibiotic administration. Manual chart abstraction was
      used to calculate door-to-antibiotic time and included 12 months of
      preintervention data and 2 months of postintervention data. RESULTS: Door-to
      antibiotic time improved from a baseline of 105.3 minutes to 71.9 minutes.
      OUTCOME: The simple change in patient throughput improved door-to-antibiotic time
      with minimal obstacles. The sepsis-screening tool implemented at triage decreased
      the door-to-antibiotic time by 33.4 minutes, without affecting triage time, and
      enhanced patient throughput of potentially septic patients.

PMID- 30195864
TI  - Recommendations for the post-operative management of an existing Warfarin therapy
      after lower limb joint arthroplasty.
AB  - BACKGROUND: Warfarin administration after lower limb joint replacements is
      associated with a high bleeding risk, creating the circumstances for
      periprosthetic joint infections, increased treatment costs and prolonged Length
      of Stay (L.o.S). We believe that previously warfarinized patients can be treated
      safely and discharged without delays, if appropriate policies are established and
      adhered to. METHODS: This is a retrospective cohort study. We have collected and
      analyzed data from an audit cycle between 2012 and 2015 on: 1) the post-operative
      Warfarin reloading protocol, identifying 4 distinct patterns: usual dose, 1.5
      times or double the usual dose for 2 days and overloading, 2) timing of
      reloading: Evening of Surgery vs post-op Day 1, 3) frequency of INR testing:
      daily vs intermittent, 4) time required to reach a therapeutic INR value >=2.0,
      5) rate of INR variations >=4.0 and 6) bleeding complications, 7) and the overall
      L.o.S. RESULTS: We found a significant difference in the time required to reach
      an INR >=2.0 between reloading with the usual dose and all other protocols (p <
      0.001) without abolishing adverse sequelae. Daily INR testing reduced bleeding
      complications and INR variations at a significant (p < 0.001) and non-significant
      level respectively, while timing of restarting showed no significant effect. We
      found a correlation between INR variations and bleeding complications (odds
      ratio: 4.65, C.I: 0.59-30.87). 41% of the cohort was discharged on the day their
      INR turned therapeutic with an average L.o.S of 6.5 days. CONCLUSION: We
      recommend to: 1) restart Warfarin at double (or in exceptional cases 1.5 times)
      the patient's maintenance dose for the first two doses, 2) starting on the
      Evening of Surgery, 3) with daily INR monitoring after the second loading dose,
      4) using point of care testing devices, 5) and dosing thereafter to be guided by
      an anticoagulation service or computer assistance.

PMID- 30195865
TI  - The impact of indocyanine-green fluorescence angiogram on colorectal resection.
AB  - BACKGROUND: Perfusion plays an important role in anastomotic healing. Indocyanine
      green fluorescence angiogram allows objective bowel perfusion assessment. This
      study aimed to investigate the impact of perfusion assessment on intraoperative
      decision during left-sided colorectal resections. METHOD: This was a prospective,
      single-centre, observational study recruiting patients with left-sided colorectal
      resections. Perfusion of bowel segment was assessed with ICG fluorescence
      angiogram prior to resection and anastomosis intra-operatively. The planned
      transection site and the actual transection site after perfusion assessment were
      compared. The decision for diversion stoma was also evaluated. RESULTS: 110
      patients with cancer of the sigmoid colon (29.1%) and rectum (70.9%) were
      recruited. Total mesorectal excision was performed in 51.8% of patients. The
      transection site was revised in 34.5% of cases: 30.9% more proximally and 3.6%
      more distally. The median distance between the intended and actual transection
      sites was 2 cm (range 1-17 cm). A proximal revision in the transection site was
      more likely seen in rectal cancers (p = 0.036, OR 3.58, 95% CI 1.09-11.78) and
      relatively under-perfused left colon (p = 0.036, OR 1.01, 95% CI 1.01-1.02).
      Three (2.7%) patients were spared from a diversion stoma. The overall anastomotic
      leakage rate was 5.5%. CONCLUSION: ICG fluorescence angiogram altered operative
      decisions in a significant proportion of cases. The impact on transection site
      was more pronounced in patients with rectal cancers and those with relatively
      under-perfused colon.

PMID- 30195866
TI  - Lespedeza cuneata protects the endothelial dysfunction via eNOS phosphorylation
      of PI3K/Akt signaling pathway in HUVECs.
AB  - BACKGROUND: Lespedeza cuneata G.Don (LCE), which belongs to the genus Lespedeza
      (Leguminosae), is a traditional oriental medicine known to prevent diabetes and
      cardiovascular diseases. However, no scientific studies about the effectiveness
      of LCE, their responsible bioactive constituents, and its mechanisms against
      endothelial dysfunction have been performed. PURPOSE: This study was performed to
      investigate the role of LCE and its chemical components in ameliorating
      endothelial dysfunction. METHODS: The production of nitric oxide (NO) was
      evaluated after LCE treatment in HUVECs. Cell viability was measured using 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reagent. Western blot
      analysis was performed to determine the protein expression of endothelial nitric
      oxide synthase (eNOS) and protein kinase B (PKB, also known as Akt) in human
      umbilical vein endothelial cells (HUVECs). RESULTS: Pretreatment with L-NAME and
      LY294002 significantly decreased the LCE-induced NO production, as well as eNOS
      and Akt phosphorylation. beta-Sitosterol and beta-Sitosterol 6'-linolenoyl-3-O
      beta-D-glucopyranoside are the bioactive constituents increase NO production as
      well as eNOS phosphorylation. CONCLUSION: Our findings suggest that LCE increase
      NO production via eNOS phosphorylation of PI3K/Akt signaling pathway.

PMID- 30195867
TI  - Anti-angiogenic activity of para-coumaric acid methyl ester on HUVECs in vitro
      and zebrafish in vivo.
AB  - BACKGROUND: Para-coumaric acid methyl ester (pCAME) is one of the bioactive
      components of Costus speciosus (Koen) Sm. (Zingiberaceae). This plant is
      traditionally used in Asia to treat catarrhal fevers, worms, dyspepsia, and skin
      diseases. PURPOSE: To investigate the anti-angiogenic activity of pCAME and its
      molecular mechanism of action. STUDY DESIGN: We investigated the anti-angiogenic
      activity of pCAME on human umbilical vein endothelial cells (HUVECs) in vitro and
      zebrafish (Danio rerio) in vivo. METHODS: In vitro cell proliferation, would
      healing, migration and tube formation assays were used, along with in vivo
      physiological angiogenic vessel formation, tumor-induced angiogenic vessel
      formation assays on zebrafish model. qRT-PCR and RNA-seq were also used for the
      target investigation. RESULTS: pCAME could inhibit the proliferation, would
      healing, migration and tube formation of HUVECs, disrupt the physiological
      formation of intersegmental vessels (ISVs) and the subintestinal vessels (SIVs)
      of zebrafish embryos, and inhibit tumor angiogenesis in the zebrafish cell-line
      derived xenograft (zCDX) model of SGC-7901 in a dose-dependent manner.
      Mechanistic studies revealed that pCAME inhibited vegf/vegfr2 and ang/tie
      signaling pathways in zebrafish by quantitative RT-PCR analysis, and regulated
      multi-signaling pathways involving immune, inflammation and angiogenesis in SGC
      7901 zCDX model by RNA-seq analysis. CONCLUSION: pCAME may be a multi-target anti
      angiogenic drug candidate and hold great potential for developing novel
      therapeutic strategy for cancer treatment.

PMID- 30195868
TI  - Oral administration of Zuccagnia punctata extract improves lipid profile, reduces
      oxidative stress and prevents vascular dysfunction in hypercholesterolemic
      rabbits.
AB  - BACKGROUND: The consumption of flavonoids has been shown to prevent
      cardiovascular diseases including atherosclerosis. In this sense, in a recent in
      vitro study we demonstrated that a rich in flavonoids extract from Zuccagnia
      punctata has beneficial effects on vascular function in aorta from
      hypercholesterolemic rabbits. PURPOSE: The aim of this study was to evaluate the
      ability of a hydroalcoholic extract from Z.puncata (ZpE) to prevent alterations
      induced by high cholesterol diet in rabbits. METHODS: The major components of the
      ZpE, flavonoids, were analyzed by using a validated reversed phase HPLC method.
      Rabbits were separated in five groups: fed standard chow (CD); CD orally
      administrated 2.5 mg, 5 mg or 10 mg GAE/day ZpE (ZpE- CD); fed 1% cholesterol
      enriched chow (HD); HD orally administrated 2.5 mg GAE/day ZpE (ZpE-HD); HD
      orally administrated 2.5 mg rosuvastatin/day (Ro-HD). All diets were
      administrated by 6 weeks. Body weights (BW), mean blood pressure (MAP), heart
      rate (HR), visceral abdominal fat (VAF), organ weight (heart, kidney, liver) and
      vascular morphology were determined. Total cholesterol (TC), triglycerides (TG),
      fasting glucose (FG), aspartate amino transferase (AST), alanine amino
      transferase (ALT), bilirubin, creatinine, thiobarbituric acids reactive
      substances (TBARS) and glutathione reduced/oxidized index were measured in serum.
      Abdominal aorta was excised and vascular function was assessed by acetylcholine
      and sodium nitroprusiate relaxation and contractile response to norepinephrine
      and angiotensin II. RESULTS: The major compounds of ZpE identified were
      chalcones: 2',4'-dihydroxy-3'-methoxychalcone and 2',4'-dihydroxychalcone. Oral
      treatment with ZpE reduced MAP, TC, TG, TBARS, aortic intima/media ratio and
      increased glutathione reduced/oxidized index in HD rabbits. No differences were
      found in AST, ALT, bilirubin or creatinine. Acetylcholine relaxation was
      normalized and contractile response to norepinephrine and angiotensin II was
      reduced in ZpE-HD. CONCLUSION: Oral administration of ZpE as natural product in
      the prevention of cardiovascular disease related with hypercholesterolemia and
      endothelial dysfunction is very promising.

PMID- 30195869
TI  - Cytotoxicity of epunctanone and four other phytochemicals isolated from the
      medicinal plants Garcinia epunctata and Ptycholobium contortum towards multi
      factorial drug resistant cancer cells.
AB  - INTRODUCTION: Resistance of cancer cells is a serious impediment to chemotherapy
      and several phytochemicals are active against multi-drug resistant (MDR)
      phenotypes. The cytotoxicity of five naturally occurring compounds: betulin (1),
      mundulea lactone (2), seputhecarpan A (3), seputheisoflavone (4) and epunctanone
      (5) was evaluated on a panel of 9 cancer cell lines including various sensitive
      and drug-resistant cell lines. The modes of action of compound 5 were further
      investigated. METHODS: The resazurin reduction assay was used to evaluate
      cytotoxicity of samples and ferroptotic cell death induced by compound 5; caspase
      Glo assay was used to detect the activation of caspases in CCRF-CEM leukemia
      cells treated with compound 5. Flow cytometry was used for cell cycle analysis in
      CCRF-CEM cells treated with compound 5, as well as detection of apoptotic cells
      by annexin V/PI staining, analysis of mitochondrial membrane potential (MMP) and
      measurement of reactive oxygen species (ROS). RESULTS: Compounds 1-5 displayed
      cytotoxic effects in the 9 studied cancer cell lines with IC50 values below 70
      uM. The IC50 values varied from 8.20 uM (in HCT116 (p53-/-) colon cancer cells)
      to 35.10 uM (against HepG2 hepatocarcinoma cells) for 1, from 8.84 uM (in
      CEM/ADR5000 leukemia cells) to 48.99 uM (in MDA-MB-231 breast adenocarcinoma
      cells) for 2, from 12.17 uM (in CEM/ADR5000 cells) to 65.08 uM (in MDA-MB-231
      cells) for 3, from 23.80 uM (in U87MG.DeltaEGFR glioblastoma cells) to 68.66 uM
      (in HCT116 (p53-/-) cells) for 4, from 4.84 uM (in HCT116 (p53-/-) cells) to
      13.12 uM (in HepG2 cells) for 5 and from 0.02 uM (against CCRF-CEM cells) to
      122.96 uM (in CEM/ADR5000 cells) for doxorubicin. Compound 5 induced apoptosis in
      CCRF-CEM cells through alteration of MMP and increase in ROS production. In
      addition to apoptosis, ferroptosis was also identified as another mode of cell
      death induced by epunctanone. CONCLUSIONS: Compounds 1-5 are valuable cytotoxic
      compounds that could be used to combat MDR cancer cells. Benzophenoe 5 is the
      most active molecule and deserve more investigations to develop new anticancer
      drugs.

PMID- 30195870
TI  - Epigallocatechin gallate attenuates mitochondrial DNA-induced inflammatory damage
      in the development of ventilator-induced lung injury.
AB  - OBJECTIVE: We aim to investigate the role of mitochondrial DNA (mtDNA), a novel
      endogenous pro-inflammatory cytokine, in the development of ventilator-induced
      lung injury (VILI). Moreover, the protective effect of epigallocatechin gallate
      (EGCG) on VILI through inhibiting local mtDNA release was examined. METHODS: From
      March 2015 to March 2016, bronchoalveolar lavage fluid (BALF) from 36 patients
      with VILI and well-matched 36 patients without VILI after major surgery were
      consecutively collected. The expression levels of mtDNA and inflammatory
      cytokines in BALF were tested. SD rats were divided into five groups: control,
      low tidal volume (7 ml/kg) group, high tidal volume (HTV, 40 ml/kg) group,
      HTV+low dose EGCG and HTV+high dose EGCG groups. BALF were collected to examine
      the expression levels of mtDNA and several inflammatory cytokines and the lung
      tissue was harvested for pathological examinations. In addition, cyclic stretch
      cell culture was used and culture media was collected to analyze expressions of
      inflammatory cytokines. Administration of mtDNA in a rat model and in vitro cell
      culturing were used to confirm its pro-inflammatory properties in the development
      of inflammatory lung injury. RESULTS: A Significant elevation of mtDNA was
      detected in BALF from patients with VILI (581 +/- 193 vs. 311 +/- 137, p < 0.05)
      and also in rats ventilated with HTV. EGCG could significantly inhibit HTV
      induced local mtDNA release and attenuate the level of inflammatory lung injuries
      (reduced infiltration of local inflammatory cells, lower lung wet/dry ratio and
      expression levels of inflammatory cytokines). The beneficial effects of EGCG on
      preventing inflammatory lung injuries were in a concentration-dependent manner.
      Meanwhile, higher expression levels of mtDNA and inflammatory cytokines were
      observed in the media of cyclic stretched cell culture compared to those in the
      control group (p < 0.05). Furthermore, intra-tracheal administration of mtDNA in
      rats could lead to a marked increase of local inflammatory cytokines and
      subsequent inflammatory lung injuries (p < 0.05). And by adding mtDNA into the
      cell culture, higher level of inflammatory cytokines in the media was detected (p
      < 0.05). EGCG also showed preventive effects on inflammatory responses on a
      concentration-dependent manner (p < 0.05). CONCLUSION: The increased expression
      level of mtDNA and subsequent inflammatory cytokines overproduction may play an
      important role in the development of VILI. EGCG may be a potential novel
      therapeutic candidate for protection against VILI by inhibiting the local release
      of mtDNA.

PMID- 30195871
TI  - Role of curcumin in the management of pathological pain.
AB  - BACKGROUND: Pathological pain conditions can be triggered after peripheral nerve
      injury and/or inflammation. It is a major clinical problem that is poorly treated
      with available therapeutics. Curcumin is a phenolic compound derived from Curcuma
      longa, being widely used for its antioxidant, anti-inflammatory and
      immunomodulatory effects. PURPOSE: This review systematically summarized updated
      information on the traditional uses of curcumin in order to explore
      antinociceptive effects in pathological pain and evaluate future therapeutic
      opportunities clinically. Moreover, some structure-activity relationships would
      greatly enrich the opportunity of finding new and promising lead compounds and
      promote the reasonable development of curcumin. METHODS: PubMed were searched and
      the literature from the year 1976 to January 2018 was retrieved using keywords
      pain and curcumin. RESULTS: This review systematically summarized updated
      information on the traditional uses, chemical constituents and bioactivities of
      curcumin, and highlights the recent development of the mechanisms of curcumin in
      the pathological pain by sciatic nerve injury, spinal cord injury, diabetic
      neuropathy, alcoholic neuropathy, chemotherapy induced peripheral
      neuroinflammtion, complete Freund's adjuvant (CFA) injection or carrageenan
      injection. Importantly, the clinical studies provide a compelling justification
      for its use as a dietary adjunct for pain relief. And we also present multiple
      approaches to improve bioavailability of curcumin for the treatment of
      pathological pain. CONCLUSION: This review focuses on pre-clinical and clinical
      studies in the treatment of pathological pain. Although the mechanisms of pain
      mitigating effects are not very clear, there is compelling evidence proved that
      curcumin plays an essential role. However, further high-quality clinical studies
      should be undertaken to establish the clinical effectiveness of curcumin in
      patients suffering from pathological pain. Potential methods of increase the
      water solubility and bioavailability of curcumin still need to be studied. These
      approaches will help in establishing it as remedy for pathological pain.

PMID- 30195872
TI  - Pharmacokinetic-pharmacodynamic modeling to study the anti-dysmenorrhea effect of
      Guizhi Fuling capsule on primary dysmenorrhea rats.
AB  - BACKGROUND: Primary dysmenorrhea (PDM) is one of the most common gynaecological
      disorders among women, which seriously affects women's life quality due to its
      high incidence rate. Guizhi Fuling capsule (GZFLC), a well-known traditional
      Chinese medical prescription, has been widely used to treat gynecological blood
      stasis syndromes such as PDM. However, its mechanisms of action and combination
      were still unknown. PURPOSE: The aim of this study was to develop a
      pharmacokinetic-pharmacodynamic (PK-PD) model to assess time-concentration-effect
      relationships for anti-dysmenorrhea effect of GZFLC and provide better
      understanding for mechanisms of action and combination of GZFLC. STUDY DESIGN AND
      METHODS: The PDM rats model was induced by oxytocin exposure following estradiol
      benzoate pretreatment. Gallic acid (GA), amygdalin (AMY), albiflorin (ALB),
      prunasin (PA) and cinnamic acid (CA) were evaluated as bioactive ingredients for
      investigating PK processes. GA, AMY, ALB and PA exhibited appropriate PK
      parameters and were selected as the PK markers to map the anti-dysmenorrhea
      effect of GZFLC. A PK-PD model was established on the basis of GA, AMY, ALB and
      PA plasma concentrations vs. the values of two ratios (PGE2/PGF2alpha and 6-Keto
      PGF1alpha/TXB2), by a two-compartment PK model with a simple Emax model to
      explain the time delay between the drug plasma concentrations of PK markers and
      the anti-dysmenorrhea effect. RESULTS: The PDM rat model has been successfully
      established. Compared with the normal treated group, the bioactive ingredients in
      PDM treated group exhibited significant changing trends of PK behaviors, such as
      better absorption and distribution, slower elimination and delays in reaching the
      maximum concentration (Tmax). The analysis of PK-PD parameters indicated that the
      active metabolites and prototypes of bioactive ingredients in GZFLC were inclined
      to regulate the activity of prostacyclin synthetase and thromboxane synthetase to
      control the production of TXA2 and PGI2 so as to treat PDM. As the main effective
      medicinal materials for the treatment of PDM in GZFLC prescription Persicae
      Semen, Moutan Cortex and Paeonia lactiflora Pall, Persicae Semen played the most
      important role, while the role of Paeonia lactiflora Pall was the weakest.
      CONCLUSION: The PK-PD model results provided scientific basis for clarifying
      compatibility mechanisms of GZFLC prescription and a better understanding for
      biosynthetic mechanisms of four prostaglandins (PGE2, PGF2alpha, 6-Keto-PGF1alpha
      and TXB2) in the treatment of PDM by GZFLC. Investigations on the relationship
      between the effects and the bioactive ingredients are of benefit to explore the
      mechanisms of action and combination for traditional Chinese medical
      prescriptions (TCP) and facilitate the development of future clinical
      applications of TCP.

PMID- 30195873
TI  - Coptisine-induced apoptosis in human colon cancer cells (HCT-116) is mediated by
      PI3K/Akt and mitochondrial-associated apoptotic pathway.
AB  - BACKGROUND: Colorectal cancer is the third leading cause of cancer-related deaths
      in the word. Coptisine (COP), an isoquinoline alkaloid derived from Coptis
      chinensis Franch, possesses a wide variety of pharmacological effects. However,
      its anti-proliferative effect on colon cancer is not fully elucidated. In the
      present study, we aimed to ascertain whether COP inhibits HCT-116 cell growth and
      to further explore the molecular mechanism in vitro and in vivo. METHODS: Cell
      viability was determined by MTT assay. Cell migration was detected using wound
      healing assay. Apoptosis, mitochondrial membrane potential (Deltapsim) and
      reactive oxygen species (ROS) was analysis via flow cytometry. Hoechst 33342 was
      used for morphology observation. The expression levels of proteins related to
      mitochondrial-mediated apoptotic pathway were detected by western blotting. In
      addition, the antitumor ability of COP was further measured in athymic nude mice.
      RESULTS: COP significantly decreased cell viability and migration in HCT-116
      cells. Flow cytometry and Hoechst 33342 analysis confirmed that COP suppressed
      cell proliferation by inducing apoptosis. COP decreased Deltapsim dose
      dependently and induced intracellular ROS production time-dependently. Western
      blotting showed that COP activated mitochondrial-associated apoptosis by down
      regulating Bcl-2, Bcl-XL, pro-caspase 3, XIAP level and up-regulating Bax, Bad,
      cytochrome c, Apaf-1, AIF and cleaved caspase-3 expression. In addition, COP also
      attenuated PI3K/Akt signaling pathway. In vivo study showed that 150 mg/kg COP
      significantly delayed the tumor development in BALB/c nude mice.
      Immunohistochemical analysis also confirmed the activated apoptosis in tumor
      tissue. CONCLUSION: The results demonstrated that COP induces apoptosis in HCT
      116 cells through PI3K/Akt and mitochondrial-associated apoptotic pathway. Our
      findings suggest that COP has potential to be a therapeutic candidate for colon
      cancer patients.

PMID- 30195874
TI  - Molecular mechanism and cytotoxicity of allicin and all-trans retinoic acid
      against CD44+ versus CD117+ melanoma cells.
AB  - BACKGROUND: All-trans retinoic acid (ATRA) is a differentiating agent that
      inhibits cancer cell growth during the cell cycle. However, despite its potent
      antitumor properties, some melanoma cells are resistant to ATRA therapy. PURPOSE:
      Here, we hypothesized that allicin can sensitize malignant melanoma cells to ATRA
      treatment. To clarify this mechanism, we determined the sensitivity to ATRA,
      allicin and allicin/ATRA in CD44+ and CD117+ melanoma cell subpopulations.
      METHODS: The CD44+and CD117+cells were sorted from A375 melanoma cell line using
      the magnetic-activated cell sorting (MACS). The potential anticancer effects of
      ATRA, allicin and allicin/ATRA were examined using cell proliferation MTT assay.
      In addition, flow cytometry was used to detect cell cycle arrest. The efficacy of
      the treatments in controlling cancer cell proliferation was assessed by
      quantitative realtime polymerase chain reaction (RT-PCR). RESULTS: Here, we
      demonstrated that CD44+ melanoma cells were more resistant to allicin and ATRA
      than CD117+ cells. Importantly, we observed that allicin sensitized melanoma cell
      to ATRA-induced cell death. The combination treatment with allicin and ATRA
      significantly reduced the IC50 value obtained for ATRA alone in CD44+ melanoma
      cells. In CD44+ cells, the IC50 value of ATRA was 37.43 +/- 0.54, while the IC50
      value of allicin/ATRA treatment was 17.53 +/- 0.2 uM. Allicin treatment resulted
      in significant increases in the percentage of cells at the G2/M and G0/G1 phases
      in the CD44+ and CD117+ cells, respectively. The combination treatment caused the
      inhibition of CD44+ and CD117+ melanoma cells at the S phases compared to ATRA
      alone. Allicin, ATRA, and allicin/ATRA increased the expression of cyclin D1 mRNA
      in both CD44+ and CD117+ cells. Allicin combination with ATRA increased the mRNA
      level of RARbeta in CD117+ cells. Furthermore, allicin alone caused a remarkable
      reduction of MMP-9 mRNA expression in both CD44+ and CD117+ cells. In contrast,
      ATRA and the combination treatment significantly increased MMP-9 gene expression
      in CD44+ cells. CONCLUSION: Overall, our results indicate that allicin reinforces
      the ATRA-mediated inhibitory effects on CD44+ and CD117+ melanoma cells and may
      provide a new approach for the treatment of malignant melanoma.

PMID- 30195875
TI  - Novel nor-monoterpenoid indole alkaloids inhibiting glioma stem cells from fruits
      of Alstonia scholaris.
AB  - BACKGROUND: Glioblastoma multiforme (GBM) is a highly aggressive and frequently
      recurrent malignant brain tumor, and to date, the clinically effective drugs
      against GBM remain scarce. Natural products play an important role in drug
      discovery, and might be the resource of antitumor agents for GSCs. Alstonia
      scholaris (L.) R. Br. is rich in monoterpenoid indole alkaloids (MIAs) and used
      extensively for treatment of tumor in the traditional medicine system of Asia.
      PURPOSE: To search for new MIAs with antitumor activity against glioma stem cells
      from clinical patients and explore their mechanism. METHODS: Compounds were
      obtained from the fruits of A. scholaris by chromatographic separation, including
      silica gel, Sephadex LH-20 and recrystallization. Their structures were
      elucidated by the use of UV, IR, NMR and MS spectra. The antitumor activity of
      the compounds against the glioma stem cells (GSC-3#, GSC-12#, GSC-18#) were
      investigated by phenotypic screening and MTS assays. Cell proliferation assay by
      BrdU immunofluorescence staining, and apoptosis assay by cleaved-caspase-3
      immunofluorescence staining and real-time PCR assay. The soft-agar clonal
      formation assay was performed to determine the antitumor efficacy of the
      compounds in vitro. RESULTS: Two new nor-monoterpenoid indole alkaloids were
      isolated from the fruits of A. scholaris. They exhibited selective antitumor
      activity against glioma stem cells (GSC-3#, GSC-12#, GSC-18#) with IC50 values of
      15-25 ug/ml. Furthermore, they inhibited GSCs proliferation, induced GSCs
      apoptosis by increasing the expression of TNF-alpha and cleavage of caspase-3,
      and significantly damaged colony forming capacity of GSCs. CONCLUSION: New nor
      monoterpenoid indole alkaloids from the fruits of A. scholaris provide new type
      promising molecule for the selective killing of human glioma stem cells.

PMID- 30195876
TI  - Nitensidine B affects proteins of the glycolytic pathway and induces apoptosis in
      cervical carcinoma cells immortalized by HPV16.
AB  - BACKGROUND: Cervical cancer, the fourth most common type of cancer among women
      worldwide, accounts for approximately 12% of all types of malignancies that
      affect women. Natural products have contributed significantly to the development
      of modern therapies; approximately 70% of the drugs available for chemotherapy
      are naturally based products. PURPOSE: The purpose of this study was to examine
      the biological activities of nitensidine B (NTB), a guanidinic alkaloid isolated
      from the leaves of Pterogyne nitens Tul. (Fabaceae) in a cervical cancer cell
      line. METHODS: In vitro experiments were performed using cervical carcinoma cells
      immortalized by human papillomavirus type 16 (HPV16, SiHa cells), since
      epidemiological and molecular studies have demonstrated robust associations
      between the etiologies of cervical cancer and HPV infection. Cytotoxicity as well
      as the effect of NTB treatment on intracellular signals of apoptosis,
      fragmentation of internucleosomal DNA via terminal deoxynucleotidyl transferase
      dUTP nick end labeling (TUNEL), and levels of apoptosis effectors (Caspase 3/7)
      were evaluated. In addition, differential proteomic analysis (iTRAQ) and protein
      validation using western blot were performed. RESULTS: The cytotoxicity of NTB
      treatment in the SiHa cell line was concentration-dependent, with the minimum
      inhibitory concentration of 50% of the cells of 40.98 uM. In the TUNEL assay,
      SiHa cell apoptosis with 3/7 caspase activation was reported at 12 h following
      treatment. Differential proteomic analysis by iTRAQ demonstrated that proteins of
      the glycolytic pathway, aldolase A, alpha-enolase, pyruvate kinase, and
      glyceraldehyde 3-phosphate dehydrogenase were underexpressed. CONCLUSION: These
      results indicated that NTB could play a role in decreasing glycolysis . Since
      tumor cells prefer the glycolytic pathway to generate energy, these findings
      suggest that NTB may be a reliable model for the study of human cervical cancer
      cell lines immortalized by HPV16, however more experiments can be performed.

PMID- 30195877
TI  - Baicalin protects mice against Salmonella typhimurium infection via the
      modulation of both bacterial virulence and host response.
AB  - BACKGROUND: The worsening problems of antibiotic resistance prompt the need for
      alternative strategies. Baicalin, which is isolated from Scutellaria
      baicalensisi, has been demonstrated to exhibit anti-inflammatory, anti-virulence
      and antimicrobial effects. Salmonella typhimurium is an important foodborne
      pathogenic bacteriaum that causes gastrointestinal disease in humans and many
      animals. PURPOSE: The aim of this study was to investigate the effects of
      baicalin on S. typhimurium infection in mice and its possible mechanism in vitro.
      STUDY DESIGN: To evaluate the effect of baicalin in vivo, mice were orally
      administered of baicalin, and then were infected by an intragastric
      administration of S. typhimurium. The minimal inhibitory concentrations (MICs)
      and minimum bactericidal concentrations (MBCs) of baicalin, baicalein, and
      oroxylin A against S. typhimurium were detected under the guides of the Clinical
      and Laboratory Standards Institute. In vitro, Caco-2 cells were infected with S.
      typhimurium in the presence or absence of baicalin, baicalein, and oroxylin A at
      sub-MICs. METHODS: In the in vivo experiment, the body weight loss, the serum
      levels of TNFalpha,  IL-6, and lactic dehydrogenase (LDH), the pathological
      changes of the caecum and the caecum bacterial burdens were examined. The MICs
      and MBCs of baicalin, baicalein, and oroxylin A against S. typhimurium were
      detected by two-fold serial dilutions. In vitro, Caco-2 cells were infected with
      S. typhimurium, and the invasion capacity, TNFalpha, nitrate, and LDH were
      analysed. The transcription levels of Salmonella pathogenicity island 1 virulence
      associated genes (sopB, sopE, sopE2) of S. typhimurium in the presence of
      baicalin, baicalein, and oroxylin A were detected by qRT-PCR. RESULTS: Our
      results showed that baicalin significantly decreased the body weight loss, the
      serum levels of TNFalpha,  IL-6, and LDH, and the caecum bacterial burdens of
      mice challenged with S. typhimurium. Histological examination showed that
      baicalin decreased the lesion in the caecum of S. typhimurium-infected mice. MICs
      and MBCs of baicalin, and oroxylin A. against S. typhimurium were > 128 ug/ml.
      MICs and MBCs of baicalein against S. typhimurium were 64 ug/ml, and > 128 ug/ml,
      respectively. Pretreatment of Caco-2 cells or S. typhimurium with baicalin,
      baicalein, and oroxylin A significantly inhibited the invasion of Caco-2 cells by
      S. typhimurium in a dose-dependent manner. Sub-MICs of baicalin, baicalein, and
      oroxylin A also significantly decreased the levels of TNFalpha, nitrate, and LDH
      from S. typhimurium-infected Caco-2 cells. Moreover, the transcription levels of
      sopB, sopE, and sopE2 were significantly suppressed by baicalin, baicalein, and
      oroxylin A. CONCLUSIONS: These results demonstrated that baicalin is a promising
      agent for the prevention of S. typhimurium infection via the modulation of both
      bacterial virulence and host response.

PMID- 30195878
TI  - Role of the serotonergic pathway in uterotonic activity of Ananas comosus (L.)
      Merr. - An in vitro and in vivo study.
AB  - BACKGROUND: Ananas comosus (L.) Merr. has been used as a traditional medicine in
      inducing abortion in many countries. Our previous in vitro experiments showed
      that the aqueous fraction (F4) of A. comosus extract stimulated the rat and human
      uterine contractions. PURPOSE: The aim of this study was to identify the
      bioactive compound and further investigate the molecular mechanism of F4 induced
      contraction and the in vivo uterotonic effect of F4. MATERIALS AND METHODS: Organ
      bath studies were employed to compare the stimulatory effect of F4 in non and
      late pregnant uterine tissue followed by isolation of protein from late pregnant
      uterine tissue for the western blot analysis. The PhysioTel transmitter was
      implanted in pregnant SD rats to measure the changes in intrauterine pressure
      (IUP). Analyses of the crude extract and active principle in F4 was performed
      using LC-HRMS. RESULTS: Ripe F4 in a similar manner as serotonin produced a
      greater stimulatory response in late pregnant than non-pregnant uterine tissue
      without significant change in potency; ripe F4 also increased ERK phosphorylation
      which eventually led to a significant increase of the final product, MMP-13. In
      pregnant rats (E18), oral ripe F4 (1.5 g.100 g-1 body weight) and ergometrine (1
      mg) did not stimulate the uterine contraction probably due to the low level of
      estradiol and as a consequence low 5-HT receptors at the time of administration.
      In contrast, in postpartum rats, oral administration of F4 and ergometrine
      produced a significant increase in maximal IUP to 4.3 and 4.9 folds of basal IUP
      respectively. Contrary to the folklore use, unripe F4 did not stimulate the
      uterine activity during pregnancy and postpartum. Bioassay guided fractionation
      identified serotonin as a major bioactive compound in ripe F4. CONCLUSIONS: Our
      data clearly indicate that the uterotonic effect of ripe F4 is mediated via the
      serotonergic pathway and suggest that serotonin rich diet may increase the
      peripheral serotonin and implicate in diverse physiological functions, including
      uterine motility.

PMID- 30195879
TI  - The anti-anaphylactoid effects of hydroxysafflor yellow A on the suppression of
      mast cell Ca2+ influx and degranulation.
AB  - BACKGROUND: Anaphylaxis is a type of potentially fatal hypersensitivity reaction
      resulting from the activation of mast cell mediators, especially histamine and
      lipid mediators. Non-IgE-mediated anaphylaxis can occur because of the direct
      activation of mast cells. Hydroxysafflor yellow A (HSYA) is the main chemical
      component of safflower (Carthamus tinctorius) and has been reported to have
      pharmacological activities. However, the anti-anaphylactoid effect of HSYA has
      not yet been investigated. PURPOSE: The aims of this study were to evaluate the
      anti-anaphylactoid activity of HSYA in vivo and to investigate the underlying
      mechanism in vitro. METHODS: The anti-anaphylactoid activity of HSYA was
      evaluated in a mouse model of hindpaw extravasation. Calcium imaging was used to
      assess intracellular Ca2+ mobilization. The levels of cytokines and chemokines
      released by stimulated mast cells were measured using enzyme immunoassay kits.
      Western blotting was used to explore the related molecular signaling pathways.
      RESULTS: HSYA markedly inhibited mast cell degranulation by suppressing the
      activation of intracellular Ca2+ mobilization and preventing the release of
      cytokines and chemokines from mast cells in a dose-dependent manner via the PKC
      PLCgamma-IP3R signaling pathway. CONCLUSION: In summary, HSYA has anti
      anaphylactoid pharmacological activity, which makes it a potential candidate for
      the development of a novel agent to suppress drug-induced anaphylactoid
      reactions.

PMID- 30195880
TI  - Curcumin enhances cisplatin sensitivity of human NSCLC cell lines through
      influencing Cu-Sp1-CTR1 regulatory loop.
AB  - BACKGROUND: Curcumin is a naturally occurring polyphenol which has been
      demonstrated to possess diverse biological activities. We previously reported
      that curcumin is a biologically active copper chelator with antitumor activity.
      Copper transporter 1 (CTR1) on the plasma membrane of eukaryotic cells mediates
      both copper as well as anticancer drug cisplatin uptake. PURPOSE: This study aims
      to investigate whether curcumin enhances cisplatin sensitivity of human non-small
      cell lung cancer (NSCLC) through influencing Cu-Sp1-CTR1 regulatory loop.
      METHODS: The combination effect of curcumin and cisplatin on cell proliferation
      and apoptosis was determined in vitro and in vivo. Platinum level in A549 cells
      and tumor tissue was measured by atomic absorption spectrometry (AAS). The
      binding ability of specificity protein 1 (Sp1) to CTR1 and Sp1 promoters was
      detected by ChIP assay and luciferase reporter assay system. RESULTS: Here we
      show that combined curcumin and cisplatin treatment markedly inhibited A549 cells
      proliferation and induced its apoptosis. Using a mouse model of A549 xenograft,
      we demonstrated that curcumin inhibits copper influx and increases uptake of
      platinum ion in tumor. Curcumin treatment enhances the binding of Sp1 to CTR1 and
      Sp1 promoters, thus induces CTR1 expression and chemosensitization to cisplatin
      treatment. This process is regulated by the Cu-Sp1-CTR1 regulatory loop.
      Moreover, the enhancement mediated by curcumin on cisplatin therapeutic efficacy
      in cultured human NSCLC cell lines (A549, H460, H1299) was dependent on CTR1.
      CONCLUSIONS: Our results demonstrated copper chelator curcumin enhances the
      benefits of platinum-containing chemotherapeutic agents and CTR1 could be a
      promising therapeutic target for non-small cell lung cancer treatment.

PMID- 30195881
TI  - Zingiber officinale extract administration diminishes steroyl-CoA desaturase gene
      expression and activity in hyperlipidemic hamster liver by reducing the oxidative
      and endoplasmic reticulum stress.
AB  - BACKGROUND: Stearoyl CoA desaturases (SCD) are enzymes that convert saturated to
      monounsaturated fatty acids and have increased activity in hepatic steatosis.
      PURPOSE: We aimed to investigate the potential of ginger extract (GIN) to
      modulate the liver SCD1 expression and activity in hyperlipidemic (HL)
      conditions, in order to lower lipid accumulation in the steatotic liver. STUDY
      DESIGN/METHODS: Male Golden Syrian hamsters were divided in three groups: (i) fed
      with standard chow (N), (ii) fed with standard chow plus 3% cholesterol and 15%
      butter for 21 weeks (HL), (iii) HL treated with GIN (800 ug/kg body weight/day)
      in the last 5 weeks of fat diet (HL-GIN). Cholesterol (C), triglycerides (TG),
      non-esterified fatty acids (NEFA), SCD1 estimated activity (C16:1n7/C16:0;
      C18:1n9/C18:0) and gene expression, acetyl-CoA carboxylase (ACC), thiobarbituric
      acid reactive substances (TBARS), paraoxonase1 (PON1) and myeloperoxidase (MPO)
      were determined in the plasma and liver of all hamsters. We measured protein
      expression of endoplasmic reticulum stress (ERS) markers, gene and protein
      expression of liver X receptor alpha/beta (LXRalpha/beta), peroxisome
      proliferator-activated receptor gamma (PPARgamma), ATP-binding cassette sub
      family G member 5/8 (ABCG5/G8) and 7alpha-hydroxylase1 (CYP7A1) in all hamsters'
      livers. RESULTS: In plasma, in HL-GIN versus HL hamsters, SCD1 estimated activity
      was lower (27%; 15%, p < 0.05), NEFA levels decreased by 91%, p < 0.001, while C
      and TG levels did not vary; the oxidative stress expressed as MPO and TBARS
      levels decreased (15%; 11%, p < 0.01), while PON1 protein increased (75%, p <
      0.05). In the liver of HL-GIN versus HL, C, TG, NEFA, MPO and TBARS levels
      decreased (8-40%, p < 0.05) and PON1 protein levels increased (30%, p < 0.05),
      SCD1 estimated activity decreased (8%; 9%, p < 0.05), in parallel with the
      reduced gene expression of SCD1 and ACC (70-80%, p < 0.05). The protein
      expression of the ERS sensors decreased (30-65%, p < 0.05), while that of
      ABCG5/G8, CYP7A1, LXRalpha/beta and PPARgamma increased in HL-GIN (20-30%, p <
      0.05) versus HL liver. CONCLUSION: GIN reduces SCD1 estimated activity and
      expression, as well as the lipids accumulated in the livers of HL hamsters. This
      is achieved through a mechanism involving the decrease of the oxidative and ERS,
      and the enhancement of cholesterol efflux.

PMID- 30195882
TI  - The effect of a garlic supplement on the pro-inflammatory adipocytokines,
      resistin and tumor necrosis factor-alpha, and on pain severity, in overweight or
      obese women with knee osteoarthritis.
AB  - BACKGROUND: Osteoarthritis (OA) is a prevalent degenerative joint disease, which
      is associated with chronic and disabling pain. The adipocytokines, resistin and
      tumor necrosis factor-alpha (TNF-alpha), might play a role in OA pathogenesis and
      outcomes. PURPOSE: The aim of this study was, therefore, to assess the anti
      inflammatory and analgesic effects of a garlic supplement on serum resistin and
      TNF-alpha concentrations and on pain severity in overweight or obese women with
      knee OA. STUDY DESIGN: Randomized, double-blind, placebo-controlled, parallel
      design trial. METHODS: In this study, 80 post-menopausal overweight or obese
      women (25 <= BMI <= 40 kg/m2, age 50-75 years) with mild to moderate knee OA were
      enrolled. Patients were randomly divided into two groups to receive twice-daily
      either garlic tablets (total: 1000 mg) or placebo for 12 weeks. The primary
      outcome measures were fasting serum concentrations of resistin and TNF-alpha, and
      pain severity (assessed using 0-10 point visual analogue scale (VAS)). RESULTS:
      At week 12, resistin concentrations were significantly decreased in the garlic
      group (6.41 +/- 2.40 to 5.56 +/- 2.16 ng/ml; P = 0.008). Serum TNF-alpha levels
      did not change significantly within or between the two groups. Pain scores were
      significantly reduced in the garlic (6.8 +/- 2 to 5.3 +/- 2.3; P = 0.002), but
      not in the placebo (6.7 +/- 2.4 to 6.2 +/- 2.5; P = 0.674), group. Pain scores
      were also significantly lower in the garlic, compared with the placebo, group
      following supplementation (5.3 +/- 2.3 vs. 6.2 +/- 2.5; P = 0.043). CONCLUSIONS:
      The findings suggest that garlic supplementation for 12 weeks might reduce pain
      severity in overweight or obese women with knee OA, which may, at least in part,
      be mediated via a reduction in the pro-inflammatory adipocytokine, resistin.

PMID- 30195883
TI  - Pyrus ussuriensis Maxim. leaves extract ameliorates DNCB-induced atopic
      dermatitis-like symptoms in NC/Nga mice.
AB  - PURPOSE: Pyrus ussuriensis Maxim. has been reported to treat the fever, cough,
      asthma, and chronic skin disease in Korean Medicine. However, there is no
      scientific evidence for the use of Pyrus ussuriensis Maxim. Leaves (PUL) extract
      or its mechanism of action in atopic dermatitis (AD). This study was performed to
      find the potential therapeutic effects of PUL on the progression of AD using in
      vitro and in vivo experimental models. METHODS: We examined the effects of PUL on
      the production of nitric oxide (NO) in RAW 264.7, Interleukin 6 (IL-6) and
      Interleukin 1beta (IL-1beta) in tumor necrosis factor alpha (TNF-alpha) -induced
      HaCaT cells, respectively. The PUL extract was topically administered to the 2,4
      Dinitrochlorobenzene (DNCB) -treated NC/Nga mice. The potential effects of PUL
      extract were evaluated by measuring the dermatitis score, scratching behavior and
      serum levels of immunoglobulin E (IgE). The Interleukin 4 (IL-4) and Interleukin
      13 (IL-13) cytokines levels were also measured in the splenocytes. In addition,
      the major components from PUL were analyzed using high performance liquid
      chromatography (HPLC). RESULTS: PUL extract significantly reduced the level of NO
      in RAW 264.7 cells, as well as IL-6 and IL-1beta in TNF-alpha-induced HaCaT
      cells. It also reduced IL-4 and IL-13 levels in splenocytes. In DNCB-treated
      NC/Nga mice, PUL extract significantly ameliorated the dermatitis severity,
      scratching tendency and transepidermal water loss (TEWL) compared to the negative
      control. Also, it normalized skin barriers with decreased production of IgE in
      mice serum. The arbutin, chlorogenic acid, and rutin were identified as major
      constituents of the extract by HPLC analysis. These constituents may be involved
      either alone or together in the regulation of atopic dermatitis. CONCLUSION: Our
      studies indicate that PUL ameliorates atopic dermatitis-like symptoms by
      suppressing the proinflammatory cytokines and immune stimuli in both in vitro and
      in vivo animal models. Therefore, these data suggest that PUL might be an
      effective natural resource for the treatment of AD.

PMID- 30195884
TI  - Drug resistance in glioblastoma and cytotoxicity of seaweed compounds, alone and
      in combination with anticancer drugs: A mini review.
AB  - BACKGROUND: Glioblastomas (GBM) are one of the most aggressive tumor of the
      central nervous system with an average life expectancy of only 1-2 years after
      diagnosis, even with the use of advanced treatments with surgery, radiation, and
      chemotherapy. There are several anticancer drugs with alkylating properties that
      have been used in the therapy of malignant gliomas. Temozolomide (TMZ) is one of
      them, widely used even in combination with ionizing radiation. However, the main
      disadvantage of using these types of drugs in the treatment of GBM is the
      development of cancer drug resistance. Research of bioactive compounds with
      anticancer activity has been heavily explored. PURPOSE: This review focuses on a
      carotenoid and a phlorotannin present in seaweed, namely fucoxanthin and
      phloroglucinol, and their anticancer activity against glioblastoma. The
      combination of natural compounds with conventional drugs is also discussed.
      CONCLUSION: Several natural compounds existing in seaweeds, such as fucoxanthin
      and phoroglucinol, have shown cytotoxic activity in models in vitro and in vivo,
      acting through different molecular mechanisms, such as antioxidant,
      antiproliferative, DNA damage/DNA repair, proapoptotic, antiangiogenic and
      antimetastic. Within the scope of interactions with conventional drugs, there are
      evidences that some seaweed compounds could be used to potentiate the action of
      anticancer drugs. However, their effects and mechanisms of action, alone or in
      combination with anticancer drugs, namely TMZ, in glioblastoma cell, still few
      explored and require more attention due to the unquestionable high potential of
      these marine compounds.

PMID- 30195885
TI  - Effect of Ginkgo biloba extract-761 on motor functions in permanent middle
      cerebral artery occlusion rats.
AB  - BACKGROUND: Ginkgo biloba extract (EGb-761) has been in use to treat variety of
      ailments including memory loss and emotional disorders usually experienced after
      ischemic stroke. However, data regarding its protective role in stroke associated
      motor dysfunction is scarce. PURPOSE: The present work was designed to
      investigate the long-term effects of EGb-761 on the motor dysfunctions associated
      with permanent middle cerebral artery occlusion (pMCAO) in rats. STUDY
      DESIGN/METHODS: Focal ischemic stroke was induced in male Sprague-Dawley rats by
      pMCAO. These rats were orally administered with EGb-761 (25, 50, 100 mg/kg) and
      positive control butylphthalide (50 mg/kg) for up to 28 consecutive days. The
      motor function was evaluated by assessing neurological scores, rotarod
      performance and gait analysis after 7, 14, 21 and 28 days. After 28 days, the
      histological examination of in frontal cortex and hippocampus was also carried
      out. RESULTS: EGb-761 treatment significantly improved motor function with better
      outcome in coordination and gait impairment rats. EGb-761 (25, 50, 100 mg/kg)
      treatment for 28 days significantly decreased the neurological scores. After 28
      days of treatment EGb-761 (50 and 100 mg/kg) significantly increased the latency
      in rotarod test, walk speed, and the body rotation, whereas, decreased the stride
      time and the left posterior swing length in gait were observed. EGb-761 (50, 100
      mg/kg). EGb-761 (50, 100 mg/kg) significantly improved the pathological changes
      related to pMCAO. CONCLUSIONS: EGb 761 could improve motor function especially
      gait impairments among pMCAO rat model related to the decreased neuronal damage.
      Therefore, it might be the potential to be explored further as an effective
      therapeutic drug to treat post stroke motor dysfunctions.

PMID- 30195886
TI  - Monitoring transient groundwater fluxes using the Finite Volume Point Dilution
      Method.
AB  - Classic estimates of groundwater fluxes are usually based on the application of
      Darcy's law, which can lead to large imprecisions in transient groundwater flow
      cases. There is a need for direct, in situ measurement techniques able to monitor
      time-variable groundwater fluxes. The investigation presented here demonstrates
      that the Finite Volume Point Dilution Method (FVPDM) is a promising technique for
      the continuous monitoring of groundwater fluxes. The experimental configuration
      consisted of monitoring transient groundwater fluxes generated by a multiple step
      pumping test, which was undertaken in the alluvial aquifer of the River Meuse,
      Liege (Belgium). Additionally, two FVPDM tests were simultaneously performed in
      two piezometers screened at two different depths in the alluvial aquifer. Tracer
      concentration changes during the FVPDM tests were interpreted as the consequences
      of Darcy flux changes in the alluvial aquifer, which was related to changes in
      the applied pumping rate. Piezometric levels were also monitored in piezometers
      located around the pumping well. The pumping test was interpreted using classical
      analytical solutions, and the FVPDM tests were interpreted using a new
      mathematical solution, which allows for calculating changes in Darcy fluxes based
      on the FVPDM tracer concentration evolution during transient groundwater flow
      conditions. The experiment demonstrated the FVPDM's ability to monitor, as well
      as be sensitive to changes in transient groundwater fluxes. The FVPDM
      interpretation also showed contrasting results between the upper part of the
      aquifer, which is made of loam and sand and slow groundwater flows prevail, and
      the lower part of the aquifer, which is made of gravels and pebbles and intense
      groundwater flows prevail.

PMID- 30195887
TI  - Electromigration experiments for studying transport parameters and sorption of
      cesium and strontium on intact crystalline rock.
AB  - This study aims to determine upscaling factors for the radionuclides'
      distribution coefficients (Kd) on crushed rocks to intact rock for the safety
      analysis of radionuclide migration from spent nuclear fuel in bedrock towards
      biosphere. Here we report the distribution coefficients for intact rock
      determined by electromigration sorption experiments and compare the results with
      those from recently performed batch sorption experiments. In total 34 rock
      samples, representing three typical rock types from Olkiluoto Finland, were
      studied in order to determine distribution coefficients, effective diffusion
      coefficients and porosities using the electromigration sorption experiments,
      formation factor experiments and porosity measurement. The parameters determined
      represent the three main parameters of geosphere used in the safety assessment of
      spent nuclear fuel disposal. The distribution coefficients of cesium and
      strontium on intact rock varied between (0.12-26.2) * 10-3 m3/kg and (1.4-13.3) *
      10-3 m3/kg, respectively, whereas recent results for crushed rock varied between
      (2-57) * 10-3 m3/kg and (17-40) * 10-3 m3/kg, respectively. This implies that
      crushing increases the distribution coefficient significantly and upscaling
      factors from 3 to 33 were determined for scaling the distribution coefficients of
      crushed rock to ones of intact rock. The determined distribution coefficients of
      cesium and strontium for intact rock can be directly applied in the safety
      assessment whereas the upscaling factors can be used to convert distribution
      coefficients determined for crushed rock into ones for intact rock. Based on the
      results for porosities and effective diffusion coefficients it was concluded that
      they do not seem to correlate with sorption parameters. However, an alteration
      state, heterogeneity and mineral content seem to be important factors affecting
      the distribution coefficients and upscaling factors.

PMID- 30195888
TI  - Corrigendum to "Chemical space screening around Phe3 in opioid peptides:
      Modulating u versus delta agonism by Suzuki-Miyaura cross-couplings" [Bioorg.
      Med. Chem. Lett. 28(13) (2018) 2320-2323].

PMID- 30195889
TI  - Iodine-mediated oxidative cyclization for one pot synthesis of new 8
      hydroxyquinaldine derivatives containing a N-phenylpyrazole moiety as pesticidal
      agents.
AB  - In continuation of our research aimed at discovery and development of new
      pesticidal agents, a series of new 8-hydroxyquinaldine derivatives containing a N
      phenylpyrazole moiety were prepared and their structures were characterized by 1H
      NMR, IR, ESI-MS and mp. Meanwhile, an efficient way of using iodine-mediated
      oxidative cyclization for one pot synthesis of these 8-hydroxyquinaldine
      derivatives containing a N-phenylpyrazole moiety was developed. The bioassay
      showed that compounds 8g and 9f exhibited potent pesticidal activities against
      both Mythimna separata Walker and Plutella xylostella Linnaeus. The structure
      activity relationships were also discussed.

PMID- 30195891
TI  - Clinical Features of Japanese Patients With Anti-alpha-enolase Antibody-Positive
      Autoimmune Retinopathy: Novel Subtype of Multiple Drusen.
AB  - PURPOSE: To evaluate clinical features of Japanese patients with anti-alpha
      enolase antibody-positive autoimmune retinopathy (anti-enolase AIR). DESIGN:
      Multicenter retrospective observational case series. METHODS: Forty-nine eyes of
      25 Japanese anti-enolase AIR patients (16 female and 9 male; mean age at first
      visit, 60.8 years) were included. Fundus characteristics, perimetry, spectral
      domain optical coherence tomography (SD-OCT), electroretinography (ERG), best
      corrected visual acuity (BCVA), and complicating systemic tumors were assessed.
      Protein localization of alpha-enolase was examined by immunohistochemistry in an
      enucleated eye of 1 patient. RESULTS: Patients were classified into 3 groups:
      multiple drusen (48%), retinal degeneration (36%), and normal fundus (16%).
      Drusen varied in size from small deposits to vitelliform-like lesions. Images on
      SD-OCT revealed dome-shaped hyperreflectivity beneath the retinal pigment
      epithelium (RPE), corresponding to drusen. Perimetry showed that ring scotoma was
      the most frequent (39%). Rod-system and/or single-flash cone responses revealed
      decreased responses in 81% of the eyes. Combined rod and cone system responses
      demonstrated significantly lower a-wave amplitudes in the degeneration group than
      in the drusen group (P = .005). BCVA was improved or maintained in 80% of the
      eyes during follow-up. Malignant or benign tumors were detected in 30% of
      patients. The RPE and photoreceptor layers were immunopositive for alpha-enolase.
      CONCLUSIONS: The drusen subtype, scarcely described in the literature, is
      suggested to characterize Japanese patients with anti-enolase AIR. The different
      funduscopic features with different functional severities may have resulted from
      antibody-mediated damage to RPE as well as photoreceptor cells.

PMID- 30195892
TI  - Longitudinal Relationship Between Retinal Diabetic Neurodegeneration and
      Progression of Diabetic Retinopathy in Patients With Type 2 Diabetes.
AB  - PURPOSE: To investigate the longitudinal relationship between diabetic retinal
      neurodegeneration and the progression of diabetic retinopathy (DR) by measuring
      macular ganglion cell-inner plexiform layer (mGCIPL) thickness in patients with
      type 2 diabetes (T2DM). DESIGN: Retrospective cohort study. METHODS: T2DM
      patients with no DR or mild nonproliferative DR (NPDR) followed up for >=4 years
      were included in this study. DR was graded according to retinal photography, and
      mean parafoveal mGCIPL thickness was measured using optical coherence tomography
      with at least a 6-month interval from baseline. Hazard ratios (HR) for predicting
      2-step progression and development of proliferative DR (PDR) were calculated
      using Cox proportional hazard modeling using baseline clinical factors. RESULTS:
      Of 87 eyes of T2DM patients, 39 (44.8%) exhibited 2-step DR progression and 6
      (6.9%) experienced progression to PDR. Patients with DR progression exhibited
      longer T2DM duration, thinner mGCIPL, greater mGCIPL thinning rate, severe
      cardiac autonomic neuropathy (CAN), lower peripheral nerve-conduction velocity,
      and higher glycated hemoglobin A1c level. Multivariate regression modeling
      revealed that baseline mGCIPL thickness (HR = 0.94), mGCIPL thinning rate (HR =
      1.924), CAN score (HR = 1.248), and conduction velocity of peripheral nerves (HR
      = 0.894) were significant predictive factors for DR progression (area under the
      curve = 0.92). CONCLUSION: Progressive loss of mGCIPL is an independent risk
      factor for progression in early-stage DR. Further assessment of autonomic and
      peripheral nerve functions can increase sensitivity in predicting aggravation of
      DR in patients with T2DM.

PMID- 30195890
TI  - Racial Differences in Rate of Change of Spectral-Domain Optical Coherence
      Tomography-Measured Minimum Rim Width and Retinal Nerve Fiber Layer Thickness.
AB  - PURPOSE: To compare race-related differences in estimated rate of change of
      Bruch's membrane opening-minimum rim width (BMO-MRW) and circumpapillary retinal
      nerve fiber layer thickness (RNFLT) in healthy, glaucoma suspect, and glaucoma
      eyes of individuals of European (ED) and African descent (AD). DESIGN:
      Prospective cohort study. METHODS: This study investigated rate of change of BMO
      MRW and RNFLT in 124 healthy, 227 glaucoma suspect, and 177 glaucoma eyes
      followed for approximately 3 years and tested with optical coherence tomography
      every 6 months. Suspect eyes had a history of untreated intraocular pressure
      (IOP) >= 22 mm Hg or suspicion of glaucoma by optic disc photograph assessment
      without repeatable abnormal standard automated perimetry (SAP) results. Glaucoma
      eyes had repeatable abnormal SAP results (GHT ONL or PSD <= 5%). Mixed-effects
      models were used to estimate the rate of change after controlling for age, mean
      follow-up IOP, central corneal thickness, axial length, and BMO area. RESULTS: A
      race-related difference in rate of change of global BMO-MRW but not average RNFLT
      in suspect eyes was observed. Rate of change of BMO-MRW was -1.82 MUm/year and 
      2.20 MUm/year in ED and AD suspect eyes, respectively (P = .03). Rate of change
      of RNFLT was -0.64 MUm/year and -0.75 MUm/year in ED and AD suspect eyes,
      respectively (P = .75). No race-related differences in change rate were found in
      healthy or glaucoma eyes. CONCLUSION: Race is an important consideration when
      assessing structural change, particularly minimum rim width, in glaucoma suspect
      eyes. Differences in rate of structural change may help explain racial
      disparities in glaucoma susceptibility.

PMID- 30195893
TI  - Avoiding hyperopic surprises after Descemet membrane endothelial keratoplasty in
      Fuchs dystrophy eyes by assessing corneal shape.
AB  - PURPOSE: It is unclear which patients unexpectantly have a hyperopic refractive
      outcome after combined Descemet membrane endothelial keratoplasty and cataract
      surgery (triple DMEK). We assessed how corneal shape predicts hyperopia after
      triple DMEK. DESIGN: Retrospective cohort study. METHODS: Patients with Fuchs
      endothelial corneal dystrophy (FECD) with Scheimpflug exams before uncomplicated
      triple DMEK at a tertiary referral center were included. The arithmetic error was
      calculated (stable postoperative refraction minus predicted refraction). Using
      multinomial logistic regression, risk ratios of >+0.5 D hyperopic and >0.5 D
      myopic arithmetic errors were calculated. RESULTS: In 112 eyes, the median
      predicted refraction was -0.43 D (interquartile range [IQR], -0.47 to -0.17) with
      an achieved refraction of -0.63 to 0.56 (IQR). The arithmetic error was 0.34 D
      (IQR, -0.22 to 0.81). A hyperopic arithmetic error was present in 46% of eyes.
      FECD eyes with an oblate posterior cornea (Q value >0) had a 3.0-times higher
      risk of hyperopic shift after triple DMEK (95% confidence interval [CI], 1.3 to
      7.0; p = 0.011), compared to spherical or prolate corneas (Q value <=0). In eyes
      with posterior Q >0, the mean prediction error was +0.50 D higher than in eyes
      with negative Q values (95% CI, 0.19 to 0.82; p = 0.002), independent of corneal
      thickness. CONCLUSIONS: Hyperopic surprises after triple DMEK particularly occur
      in corneas that are flatter centrally than the periphery because of edematous
      changes (oblate posterior profile). Eyes with a positive Q value on Scheimpflug
      imaging should be considered for additional power at the intraocular lens level.

PMID- 30195894
TI  - Intraocular Pressure Measurement Accuracy and Repeatability of a Modified
      Goldmann Prism: Multicenter Randomized Clinical Trial.
AB  - PURPOSE: To clinically evaluate a modified surface Goldmann applanation tomometer
      (GAT) prism for intraocular pressure (IOP) accuracy, repeatability, and safety.
      DESIGN: Prospective, open-label, randomized, controlled, multicenter reference
      device reliability and validity analysis. METHODS: A GAT and a modified surface
      GAT prism measured IOP on 173 unique eyes. The study design and analysis complied
      with FDA 510(k) and ANSIZ80.10-2014 guidelines. All eyes were randomized to IOP
      measurement by 1 of 5 standard prisms or 5 modified prisms, each from a different
      manufacturing lot. Pressures were measured by 6 investigators, 2 times with each
      prism, for a total of 1384 IOP measurements. Analysis included Bland-Altman
      difference accuracy, intraoperator and interoperator IOP measurement, and
      manufactured lot repeatability. RESULTS: Bland-Altman indicated no IOP
      measurements pairs outside the +/-5 mm Hg guidelines. Operator and manufactured
      lot repeatability F tests and 1-way ANOVAs indicated no statistical difference
      between the standard and modified prisms (all P > .10). The difference in IOP
      measurements of the standard and modified prisms correlated well to Dresdner
      central corneal thickness (CCT) correction (P = .01). CONCLUSION: A modified
      surface replacement prism is statistically equivalent to a flat-surfaced prism.
      The modified surface prism indicated statistically significant correction for CCT
      requiring further testing outside the ANSI standard limits (0.500 mm < CCT <
      0.600 mm) to examine its full potential.

PMID- 30195895
TI  - Are Risk Factors for Growth of Choroidal Nevi Associated With Malignant
      Transformation? Assessment With a Validated Genomic Biomarker.
AB  - PURPOSE: To test the hypothesis that widely used clinical risk factors for growth
      of choroidal nevi are associated with malignant transformation. METHODS: Fine
      needle biopsy for assignment of gene expression profile (class 1 or class 2) was
      performed in 207 choroidal melanocytic tumors < 3.5 mm in thickness. The class 2
      profile was employed as a validated biomarker for malignant transformation. The
      following data were collected: patient age and sex, tumor diameter and thickness,
      distance of posterior tumor margin from the optic disc, and the presence or
      absence of serous retinal detachment, orange lipofuscin pigment, drusen, retinal
      pigment epithelial fibrosis, retinal pigment epithelial atrophy, visual symptoms,
      and documented tumor growth. RESULTS: Clinical features associated with the class
      2 profile included patient age > 60 years and tumor thickness > 2.25 mm (Fisher
      exact test, P = .002 for both). Documented growth was not associated with the
      class 2 profile (P = .5). The odds ratio of a tumor having the class 2 profile
      was 2.8 (95% confidence interval 1.3-5.9) for patient age > 60 years and 3.5 (95%
      confidence interval 1.4-8.8) for tumor thickness > 2.25 mm. For patients with
      both risk factors, the "number needed to treat" to identify 1 patient with a
      class 2 tumor was 4.3 (P = .0002). No other clinical feature or combination of
      features was associated with the class 2 profile. CONCLUSIONS: None of the widely
      used choroidal nevus risk factors for tumor growth, nor documented growth itself,
      is pathognomonic of malignant transformation as defined by class 2 gene
      expression profile. Patient age and tumor thickness may be helpful for
      identifying small choroidal melanocytic tumors that are more likely to have the
      class 2 profile. Observation for growth prior to treatment continues to be
      reasonable for most patients with suspicious choroidal nevi.

PMID- 30195896
TI  - Impact of resection on overall survival of recurrent Glioblastoma in elderly
      patients.
AB  - OBJECTIVES: Glioblastoma multiforme (GBM) mostly affects elderly patients.
      Adequate therapy especially in case of tumor recurrence is still under
      discussion, since most studies focus on patients under 65 years. We evaluated the
      impact of second surgery in regard to progression free survival (PFS) and overall
      survival (OAS) in elderly patients. PATIENTS AND METHODS: 59 patients with
      recurrent glioblastoma multiforme were retrospectively evaluated. Patients were
      divided into three subgroups: stereotactic biopsy (STX), resection and second
      resection. Second and third group were pooled as "surgery" after first diagnosis.
      The median age for all groups was 71 years.The primary endpoint was overall
      survival. Statistical analysis was calculated using Kaplan-Meier analysis and
      SPSS. RESULTS: OAS was significantly longer for patients who had undergone
      surgery compared to the STX group. For patients who underwent reresection OAS was
      not significantly longer. Age (over 71) had no significant effect on OAS. PFS was
      significantly increased in patients who underwent surgery compared to those who
      underwent STX. PFS was not significantly longer in patients who underwent second
      resection. Furthermore PFS was not significantly different between patients under
      71 and over. CONCLUSION: OAS and PFS were significant increased for patients who
      underwent surgery compared to only STX. Patients showed prolonged survival of
      almost 4 months after they underwent reresection (p > 0.05). Therapy of elderly
      patients with GBM remains an individual decision with priority on quality of
      life. Clinical status, comorbidities and family background) should be taken into
      account.

PMID- 30195897
TI  - Late-onset cerebral vasculopathy complicating pneumococcal meningitis. A case
      report with unusual clinical features.

PMID- 30195898
TI  - C5 palsy following posterior decompression and instrumentation in cervical
      stenosis: Single center experience and review.
AB  - OBJECTIVE: Causation and avoidance of C5 palsy after laminectomy have proven
      elusive, with multiple factors incriminated including width of the laminectomy,
      spinal cord migration, C5 neural foraminal stenosis, or intraoperative C5 root
      traction. In an attempt to identify risk factors for C5 palsy after decompression
      in cervical stenosis and myelopathy, the following review was conducted. This
      report is from a single center with consistent criteria for diagnosis and
      management of cervical stenosis and myelopathy. PATIENTS AND METHODS: We
      retrospectively reviewed 63 patients with cervical stenosis and myelopathy who
      had been treated with laminectomy with instrumentation at the C4-6 level. Imaging
      studies reviewed included plain X-ray films, magnetic resonance imaging (MRI),
      and computed tomography (CT) scans of the cervical spine. Health-related outcomes
      were assessed before and at follow-up and included Visual Analog Scale (VAS) for
      pain (1-10), Japanese Orthopedic Association (JOA) score for myelopathy (0-18),
      and SF-36 physical functioning, energy and fatigue, and general health categories
      (0-100). RESULTS: In 53 patients (control group), decompression and
      instrumentation was accomplished without incident, but 5 patients developed
      lasting postoperative C5 palsy. At follow-up, there were overall significant
      improvements in VAS, JOA, and SF-36 physical functioning and general health
      domains. Subsequent to surgery, a loss of lordosis of 5 degrees  and an increase
      in C2 sagittal vertical axis (SVA) of 17 mm was significant. There was, however,
      no significant difference between control and C5 palsy patients in lordosis and
      C2 SVA, before or after surgery. Postoperative MRI studies were obtained in 15 of
      the control patients and 6 of the C5 palsy patients. Postoperative width of the
      laminectomy as well as the caliber of the C5 neural foramina in the control and
      C5 palsy cohorts were not statistically different. Though the posterior
      displacement of the cord in the C5 palsy cohort was larger than in controls, this
      difference was also not significant. CONCLUSION: The above findings suggest that
      the cause of C5 palsy remains elusive. Though our incidence of lasting C5 palsy
      subsequent to laminectomy and instrumentation was 8%, it is probably under
      reported. In our experience, laminectomy and instrumentation failed to increase
      lordosis and, in fact, were associated with an increase in positive cervical
      balance. Complications with cervical laminectomy and instrumentation are not by
      any means rare, and need to be emphasized in counselling patients, and selecting
      the approach.

PMID- 30195899
TI  - The functions of active listening responses.
AB  - In the literature, an interlocutor's active listening responses such as "hmh" are
      often defined as "continuers", serving to prolong another interlocutor's turn.
      However, to date, experiments on the effect of non-interruptive active listening
      responses on a conversational partner's duration of talk have given contradictory
      results. Studies have shown one interlocutor's active listening responses to
      correlate sometimes with longer and sometimes with shorter turns of another
      interlocutor. To investigate this contradiction, the effect of a confederate's
      active listening on German participants' (N = 32) duration of speech was tested
      individually in an experiment simulating two significant conversational contexts
      extracted from the literature: explaining and socializing. The effect of active
      listening responses on the duration of talk interacted significantly with the
      conversational context. When socializing, the confederate's active listening led
      participants to talk longer. Whereas in the explanatory context, this effect was
      absent, indicating that the function of active listening responses is context
      dependent.

PMID- 30195900
TI  - Hydrogel from acellular porcine adipose tissue accelerates wound healing by
      inducing intradermal adipocyte regeneration.
AB  - As an important component of the skin, intradermal adipocytes are closely
      associated with skin homeostasis and wound healing. Although studies have focused
      on the role of fibroblasts, keratinocytes, and inflammatory cells in wound
      healing, the role of adipocytes has not been fully investigated. Here, we
      verified whether the induction of adipocyte regeneration in a wound bed can
      effectively promote wound healing, finding that the hydrogel from acellular
      porcine adipose tissue (HAPA) in combination with adipose-derived stem cells
      (ADSCs)can induce in situ adipogenesis in the wound microenvironment. The newly
      regenerated adipocytes enhanced fibroblast migration, accelerated wound closing,
      and enhanced wound epithelialization. More importantly, newly formed, intact skin
      structure was observed after treating the wound with ADSCs-loaded HAPA. These
      results demonstrated that HAPA might substantially improve re-epithelialization,
      angiogenesis, and skin-appendage regeneration, making it a promising therapeutic
      biomaterial for skin-wound healing.

PMID- 30195901
TI  - Differential antiviral activity of European sea bass interferon-stimulated 15
      protein (ISG15) against RGNNV and SJNNV betanodaviruses.
AB  - ISG15 is an antiviral protein acting intracellularly, by conjugation to viral or
      cellular proteins, or extracellularly, as cytokine. In this work, an in vitro
      system, consisting of E-11 cells over-expressing European sea bass ISG15
      (Dl_ISG15_E11 cells), has been developed to evaluate the European sea bass ISG15
      protein activity against RGNNV and SJNNV isolates. Regarding RGNNV, RNA2 copy
      number and viral titres were similar in E-11 and Dl_ISG15_E11 cells, and the
      cellular survival analyses demonstrated that Dl_ISG15_E11 cells were not
      protected from this virus. In contrast, ISG15 compromises SJNNV replication,
      since a reduction of the SJNNV genome synthesis has been recorded. The ISG15 anti
      SJNNV activity was confirmed by viral titration and survival assays. In addition,
      a role of the intracellular ISG15 in modulating the transcription of endogenous
      genes has being recorded, with tlr3 gene being knocked out and e3 gene being up
      regulated in RGNNV-inoculated Dl_ISG15_E11 cells. Sea bass ISG15 has also been
      detected extracellularly, and its activity has been evaluated by co-culture. The
      survival rate of RGNNV-inoculated E-11 cells increased from 25% to 46% when they
      were co-cultured with ISG15-producing cells. Similarly, the survival rate of
      SJNNV-inoculated E-11 cells increased from 27% to 51% in co-culture with ISG15
      producing cells. To our knowledge, this is the first description of a
      differential antiviral activity of an ISG15 protein against two betanodavirus
      species, and the first evaluation of the cytokine-like activity of a fish ISG15
      protein on non-immune cells.

PMID- 30195902
TI  - Modulation of growth performance and nonspecific immunity of red swamp crayfish
      Procambarus clarkia upon dietary fulvic acid supplementation.
AB  - An eight-week experiment was conducted to determine the effects of dietary fulvic
      acids (FAs) on the growth performance, digestive enzymes and nonspecific immunity
      of red swamp crayfish Procambarus clarkia. Three diets supplemented with three
      different levels of FAs (0.1, 0.5 and 1 g kg-1) were formulated and tested for
      the growth performance, digestive enzymes and nonspecific immunity of the
      crayfish, and a diet without FAs served as control. After eight weeks of feeding,
      survival rate, phenoloxidase activity, superoxide dismutase activity, glutathione
      peroxidase level, total haemocyte count and number of hyaline cells, semigranular
      cells and granular cells and resistance to Aeromonas hydrophila of crayfishes fed
      with FA-containing diets were higher than those of the control. Moreover, based
      on the efficiency of FAs on the growth performance and nonspecific immunity of
      crayfish, the optimum dose of FAs was found to be 0.5 g (kg diet)-1. A high level
      of FA administration (1 g kg-1) did not further increase the efficiency of FAs
      compared with those in the moderate group (0.5 g kg-1, p > 0.05). Results
      indicated that oral administration of FA-containing diets can enhance the growth
      performance, intestinal digestive enzymes, immune responses and resistance of
      crayfish to infection by A. hydrophila. Thus, FAs may be utilized as a diet
      supplement for crayfish.

PMID- 30195903
TI  - Single and repetitive microplastics exposures induce immune system modulation and
      homeostasis alteration in the edible mussel Mytilus galloprovincialis.
AB  - Seashore invertebrates such as mussels are exposed to multiple bouts of pollution
      related to human activities. Plastic debris originating from land-based
      activities are a concerning issue as they may be fragmented in smaller pieces
      (microplastics, < 5 mm diameter) which have an excellent potential for uptake by
      a large variety of animals. Here, we set out to explore the whole transcriptome
      profiling of Mytilus galloprovincialis associated with temporal variability of
      microplastics concentrations. Mussels were submitted to (i) a single 18 days
      exposure to a concentration of microplastics found during pollution events (4.6
      E+5 polyethylene microbeads L-1), (ii) a recovery period to investigate the
      reversibility of microplastics effects and (iii) a repeated exposure to
      microplastics to evidence acclimation to microplastics pollution events. Overall,
      18 days-exposure to microplastics was mostly associated with disruption of mussel
      global homeostasis resulting in the production of stress and immune-related
      proteins and as a consequence, a diminution of energy allocated to growth. During
      the recovery period, a contrasting response was observed with the activation of
      apoptotic processes and the up-regulation of immune-receptors and stress-related
      proteins (glutathione peroxidase, hsp70) in mussels previously exposed to
      microplastics. These divergent responses, suggest that the establishment of
      compensatory mechanism as an attempt to recover, is not sufficient to counteract
      physiological stress induced by the first exposure. Finally, the differences
      observed in gene expression between single and repeated exposures to
      microplastics suggest, under the experimental conditions tested, that mussels may
      be able to establish a stress-memory upon microplastics exposure.

PMID- 30195904
TI  - A multi-CRD C-type lectin gene Cnlec-1 enhance the immunity response in noble
      scallop Chlamys nobilis with higher carotenoids contents through up-regulating
      under different immunostimulants.
AB  - C-type lectins have a variety of immunological functions in invertebrates. In
      order to investigate whether C-type lectin gene and carotenoids do have immune
      influences on noble scallop Chlamys nobilis under pathogen stress, acute
      challenges lasting 48 h to Vibrio parahaemolyticus, lipopolysaccharide (LPS),
      polyinosinic polycytidylic acid (Poly I: C), and PBS were conducted in noble
      scallop with different carotenoids content. A multi-CRD C-type lectin gene called
      Cnlec-1 was cloned and its transcripts under different challenges were
      determined. Full length cDNA of Cnlec-1 is 2267 bp with an open reading frame
      (ORF) of 1845 bp encoding 614 deduced amino acids, containing four carbohydrate
      recognition domains (CRD1, CRD2, CRD3 and CRD4). Phylogenetic tree analysis
      showed that CRDs of Cnlec-1 were clustered with CRDs of shellfish C-type lectins,
      especially closely related to Chlamys farreri and Argopecten irradians CRDs.
      Cnlec-1 transcripts were detected in hemocytes, mantle, gonad, kidney,
      intestines, gill and adductor. Compared with PBS control group, Cnlec-1
      transcripts were up-regulated in V. parahaemolyticus, LPS and Poly I: C groups.
      Furthermore, Cnlec-1 transcript levels of Golden scallops were significantly
      higher than that of Brown ones at 3-48 h (P < 0.05) in V. parahemolyticus groups,
      at 24 h in LPS groups and at 12-24 h in Poly I: C groups. These results
      suggesting that Cnlec-1 is an important immune factor involved in the defense
      against pathogens in the noble scallop, and carotenoids can enhance the immunity
      of noble scallop through up-regulating Cnlec-1 to different immunostimulants.

PMID- 30195905
TI  - Molecular characterization of a hepcidin homologue in starry flounder
      (Platichthys stellatus) and its synergistic interaction with antibiotics.
AB  - Hepcidins are small cysteine-rich antimicrobial peptides that play an important
      role in host immunity against pathogenic organisms. Most fish hepcidins exert
      bactericidal activities against a wide range of pathogens. In this study, we
      identified a cDNA sequence encoding a hepcidin homologue (PsHepcidin) in the
      starry flounder Platichthys stellatus. The predicted amino acid sequence of
      PsHepcidin comprises a signal peptide and a prodomain, which are followed by the
      mature peptide. Sequence analysis revealed that PsHepcidin belongs to the fish
      HAMP2 cluster and that it is closely related to mudskipper hepcidin-2. Expression
      of PsHepcidin mRNA was detected in all examined immune-related tissues, with the
      highest transcript levels being found in the liver. In response to
      lipopolysaccharide treatment, PsHepcidin was significantly up-regulated in the
      liver, kidney, and spleen in a time-dependent manner. Chemically synthesized
      mature peptides of PsHepcidin were found to exhibit broad antimicrobial activity
      in vitro. We also investigated the combined effect of PsHepcidin and conventional
      antibiotics and found that these combinations showed synergistic effects against
      most of the examined bacterial strains. Collectively, the results of this study
      indicate that PsHepcidin exhibits potent antibacterial activity both
      independently and when used in combination with conventional antibiotics.

PMID- 30195906
TI  - High-throughput sequencing analysis of microRNAs in gills of red swamp crayfish,
      Procambarus clarkii infected with white spot syndrome virus.
AB  - MicroRNAs (miRNAs) are important posttranscriptional regulators. They play an
      important role in the antiviral innate immunity of invertebrates. In the present
      study, high-throughput small RNAs Illumina sequencing systems were carried out to
      identify differentially expressed miRNAs (DEMs) in the gills of Procambarus
      clarkii, which was challenged with white spot syndrome virus (WSSV). Our results
      identified 11,617 known and 6 novel miRNAs in normal group (NG) and WSSV
      challenged group (WG) small RNA libraries. Additionally, 27 DEMs were shown to
      participate in the antiviral innate immunity of P. clarkii and were significantly
      upregulated or downregulated. In addition, the results of the KEGG pathway
      prediction of the DEMs target genes showed that putative target genes of these 27
      DEMs were related mainly to the RNA transport pathway, tight junction pathway,
      mRNA surveillance pathway, regulation actin cytoskeleton pathway, focal adhesion
      pathway, and MAPK signaling pathway. These results provide important information
      for future studies about the antiviral innate immunity of crustaceans.

PMID- 30195907
TI  - Regulation of apoptosis-related genes during interactions between oyster
      hemocytes and the alveolate parasite Perkinsus marinus.
AB  - The alveolate Perkinsus marinus is the most devastating parasite of the eastern
      oyster Crassostrea virginica. The parasite is readily phagocytosed by oyster
      hemocytes, but instead of intracellular killing and digestion, P. marinus can
      survive phagocytosis and divide in host cells. This intracellular parasitism is
      accompanied by a regulation of host cell apoptosis. This study was designed to
      gain a better understanding of the molecular mechanisms of apoptosis regulation
      in oyster hemocytes following exposure to P. marinus. Regulation of apoptosis
      related genes in C. virginica, and apoptosis-regulatory genes in P. marinus, were
      investigated via qPCR to assess the possible pathways involved during these
      interactions. In vitro experiments were also carried out to evaluate the effect
      of chemical inhibitors of P. marinus antioxidant processes on hemocyte apoptosis.
      Results indicate the involvement of the mitochondrial pathway (Bcl-2, anamorsin)
      of apoptosis in C. virginica exposed to P. marinus. In parallel, the antioxidants
      peroxiredoxin and superoxide dismutase were regulated in P. marinus exposed to C.
      virginica hemocytes suggesting that apoptosis regulation in infected oysters may
      be mediated by anti-oxidative processes. Chemical inhibition of P. marinus
      superoxide dismutase resulted in a marked increase of reactive oxygen species
      production and apoptosis in infected hemocytes. The implication of oxygen
      dependent apoptosis during P. marinus infection and disease development in C.
      virginica is discussed.

PMID- 30195908
TI  - Characterization of an immune deficiency (IMD) homolog from the oriental river
      prawn, Macrobrachium nipponense.
AB  - The immune deficiency (IMD) signal pathway mediates innate immunity against Gram
      negative bacteria in crustaceans. In the present study, an IMD homolog (MnIMD)
      from the oriental river prawn, Macrobrachium nipponense was identified. The full
      length cDNA of MnIMD was 782bp with an open reading frame of 549 bp that encodes
      a putative protein of 182 amino acids including a death domain at the C-terminus.
      Multiple alignment analysis showed that IMDs in prawn M. nipponense and other
      crustaceans shared high similarity. The recombinant protein of MnIMD was
      expressed and purified for further functional analyses. Western blot analysis
      indicated that MnIMD was present in many tissues, but with the highest level in
      the gills, which was consistent with the qRT-PCR results. After Vibrio
      parahaemolyticus challenge, MnIMD was significantly induced in gills. RNA
      interference analysis showed that the IMD pathway was involved in regulating the
      expression of different antimicrobial peptide (AMP) genes, including Cru4 and
      Cru6. These results are helpful in promoting research on the innate immunity in
      M. nipponense.

PMID- 30195909
TI  - Differential expression of microRNAs in Portunus trituberculatus in response to
      Hematodinium parasites.
AB  - Latest studies have indicated that microRNAs (miRNAs) play important roles in
      defending against bacterial and viral infections in marine crustacean, whereas
      little is known regarding the immunological roles of crustacean miRNAs in
      response to parasitic infection. To further reveal the host-parasite interactions
      between the parasitic dinoflagellate Hematodinium and its crustacean hosts, we
      applied the high-throughput sequencing technology to identify and characterize
      miRNAs in the Chinese swimming crab Portunus trituberculatus challenged with the
      Hematodinium parasite at a timescale of 16 days (d). A total of 168 miRNAs were
      identified and 51 miRNAs were differentially expressed in the hepatopancreas
      tissues of affected hosts. Eleven of the differentially expressed miRNAs were
      selected and verified by the quantitative real-time RT-PCR (qRT-PCR), manifesting
      the consistency between the high throughout sequencing and qRT-PCR assays.
      Further analysis of the putative target genes indicated that various immune
      related pathways (e.g. endocytosis, Fc gamma R-mediated phagocytosis, lysosome,
      ECM-receptor interaction, complement and coagulation cascades, antigen processing
      and presentation, focal adhesion, etc.) and signal transduction pathways (e.g.
      JAK-STAT signaling pathway, MAPK signaling pathway, p53 signaling pathway, etc.)
      were mediated by the differentially expressed miRNAs. The results presented
      fundamental knowledge on the immunological roles of crustacean miRNAs and
      contributed to the better understanding of hosts' miRNAs-mediated immunity
      against the parasitic infection.

PMID- 30195910
TI  - Activation of BDNF-TrkB signaling pathway-regulated brain inflammation in
      pentylenetetrazole-induced seizures in zebrafish.
AB  - Seizures are sustained neuronal hyperexcitability in brain that result in loss of
      consciousness and injury. Understanding how the brain responds to seizures is
      critical to help developing new therapeutic strategies for epilepsy, a
      neurological disorder characterized by recurrent and unprovoked seizures.
      However, the mechanisms underlying seizure-dependent alterations of biological
      properties are poorly understood. In this study, we analyzed gene expression
      profiles of the zebrafish heads that were undergoing seizures and identified 1776
      differentially expressed genes. Gene-regulatory network analysis revealed that
      BDNF-TrkB signaling pathway positively regulated brain inflammation in zebrafish
      during seizures. Using K252a, a TrkB inhibitor to block BDNF-TrkB signaling
      pathway, attenuated pentylenetetrazole (PTZ)-induced seizures, which also
      confirmed BDNF-TrkB mediated inflammatory responses including regulation of
      il1beta and nfkappab, and neutrophil and macrophage infiltration of brain. Our
      results have provided novel insights into seizure-induced brain inflammation in
      zebrafish and anti-inflammatory related therapy for epilepsy.

PMID- 30195911
TI  - Molecular characterization and function analysis of a nucleotide excision repair
      gene Rad23 from Litopenaeus vannamei after Vibrio alginolyticus challenge.
AB  - Nucleotide excision repair (NER) removes many different types of DNA lesions, and
      NER related host factors are reported to aid recovery steps during viral
      integration. Here, we report the identification and characterization of a DNA
      repair gene Rad23 from Litopenaeus vannamei and explore its role in innate
      immunity of crustaceans. LvRad23 contains a1149 bp open reading frame (ORF) which
      encodes a 382 amino acids protein with predicted theoretical isoelectric point of
      4.21. LvRad23 was ubiquitously expressed in the muscle, eyestalk, gill, stomach,
      heart, legs, intestine, and hepatopancreas in order from high to low and LvRad23
      protein was showed to be located in the cytoplasm of Drosophila S2 cells. The
      homology analysis showed that it has a high sequence homology with Rad23 protein
      from Marsupenaeus japonicus. Vibrio alginolyticus challenge induced a remarkable
      up-regulation of LvRad23 mRNA in hepatopancreas. Knocking down LvRad23can
      interfere the NER pathway by down regulating the expression of replication
      protein A (RPA) and proliferating cell nuclear antigen (PCNA). However it didn't
      cause any significant difference on total hemocyte count (THC) between LvRad23
      silenced and non-silenced group.LvRad23-silenced then challenge with V.
      alginolyticus inducing high level of reactive oxygen species (ROS) and DNA damage
      in hemolymph. As well as decreased THC, which seriously diminished the innate
      immune system of L. vannamei. Meanwhile, the NER pathway was reactived by
      enhancing the expression of LvRad23 and promoting the production of LvPCNA to
      resist apoptosis and maintain proliferation of hemolymph cells in the later
      stage. Our results suggest that LvRad23 plays a vital role in shrimp specific
      immune response to V. alginolytcus through its participation in NER pathway.

PMID- 30195912
TI  - Ameliorating effects of dietary mixture of Withania somnifera root extract and
      vitamin C in Labeo rohita against low pH and waterborne iron stresses.
AB  - The present study was conducted to elucidate the possible effect of a combination
      of Withania somnifera (Ashwagandha) root extract and dietary L-ascorbic acid
      (vitamin C) on the immune responses and survivability in Labeo rohita fingerlings
      against low pH and waterborne iron toxicity. Four diets were prepared containing
      0% (control), 0.01% (T1), 0.1% (T2) and 1.0% (T3) of a combination of Withania
      somnifera (Ashwagandha) root extract and dietary L-ascorbic acid (vitamin C) at
      the rate of 1:1 (w/w). Fishes were fed for 60 days to find out the best dose and
      duration of feeding by examining different haematological (haemoglobin,
      haematocrit, total RBC count, total WBC count, MCV, MCH and MCHC), immunological
      (NBT, lysozyme and total immunoglobulin activity) and biochemical (glucose, total
      protein, ALP, SGPT and SGOT level) parameters on 7, 15, 30 and 60 days of
      feeding. The best response was observed in fish fed with diet T3 within 15 days.
      The result showed a significant (p < 0.05) increase in haemoglobin, haematocrit,
      total RBC count, total WBC count, NBT, lysozyme activity, total immunoglobulin
      and total protein whereas a significant (p < 0.05) decrease in glucose, ALP, SGPT
      and SGOT level compared to control. Challenged study against waterborne iron
      (6.02 mg l-1) and low pH (4.2-4.5) after feeding the fish for 15 days with diet
      T3 showed significantly (P < 0.05) higher protection than control. The study
      concludes that inclusion of 1.0% Withania somnifera (Ashwagandha) root extract
      and dietary L-ascorbic acid (vitamin C) combination in diet have a stimulatory
      effect on immune response and reduces the effect of multiple stresses (i.e., low
      pH and waterborne iron toxicity) in L. rohita fingerlings.

PMID- 30195913
TI  - Purification and characterization of an antimicrobial peptide mytichitin-chitin
      binding domain from the hard-shelled mussel, Mytilus coruscus.
AB  - An antimicrobial peptide with 55 amino acid residues was purified by C18 reversed
      phase high-performance liquid chromatography (HPLC) from foot extract of the hard
      shelled mussel, Mytilus coruscus. This peptide showed strong antimicrobial
      activity against Gram-positive and Gram-negative bacteria, as well as fungi. The
      purified peptide was determined to have a molecular mass of 6202 Da by matrix
      assisted laser desorption/ionization time-of-flight mass spectrophotometry (MALDI
      TOF/MS). The identified 20-amino acid sequence of the purified peak by Edman
      degradation shared 100% identity with the N-terminal regions of mytichitin-1,
      mytichitin-2, mytichitin-3, mytichitin-4, mytichitin-5, and chitinase-like
      protein-1, and so was named mytichitin-CBD. The cDNA of mytichitin-CBD was cloned
      and sequenced by rapid amplification of cDNA ends (RACE). The mRNA transcripts
      were mainly detected in foot tissue, and they were up-regulated and peaked at 4 h
      after bacterial infection. We constructed and expressed recombinant mytichitin
      CBD protein which displayed antimicrobial activity against Gram-negative bacteria
      Gram-positive bacteria and the fungus as well as anti-parasitic activity against
      scuticociliates. The results of this study demonstrate that the peptide isolated
      from M. coruscus is related to the innate immune system of this marine
      invertebrate and is a possible alternative to antibiotics.

PMID- 30195914
TI  - Cyprinid viral diseases and vaccine development.
AB  - In the past decades, global freshwater fish production has been rapidly growing,
      while cyprinid takes the largest portion. Along with the rapid rise of novel
      forms of intensive aquaculture, increased global aquatic animal movement and
      various anthropogenic stress to aquatic ecosystems during the past century,
      freshwater fish farming industry encounter the emergence and breakout of many
      diseases, especially viral diseases. Because of the ability to safely and
      effectively prevent aquaculture diseases, vaccines have become the mainstream
      technology for prevention and control of aquatic diseases in the world. In this
      review, authors summarized six major cyprinid viral diseases, including koi
      herpesvirus disease (KHVD), spring viraemia of carp (SVC), grass carp hemorrhagic
      disease (GCHD), koi sleepy disease (KSD), carp pox disease (CPD) and herpesviral
      haematopoietic necrosis (HPHN). The present review described the characteristics
      of these diseases from epidemiology, pathology, etiology and diagnostics.
      Furthermore, the development of specific vaccines respective to these diseases is
      stated according to preparation methods and immunization approaches. It is hoped
      that the review could contribute to aquaculture in prevention and controlling of
      cyprinid viral diseases, and serve the healthy and sustainable development of
      aquaculture industry.

PMID- 30195915
TI  - Zebrafish intelectin 1 (zITLN1) plays a role in the innate immune response.
AB  - Intelectin displays carbohydrate binding capacity and has been demonstrated to
      agglutinate bacteria, suggesting its role in innate immunity. It has also been
      linked to many pathogenic conditions in human. After reporting two amphioxus
      orthologs and the zebrafish intelectin 2 (zITLN2), here we cloned and
      characterized zebrafish intelectin 1 (zITLN1). Like zITLN2, zITLN1 also contains
      a conserved fibrinogen-related domain (FReD) and a unique intelectin domain (ITLN
      D), expresses in all the tissues tested, with the highest level in intestine, and
      responds to bacterial challenge in acute phase. We also expressed zITLN1 in E.
      coli system, and purified recombinant zITLN1 could agglutinate both Gram-positive
      and Gram-negative bacteria in a calcium dependent manner. Its ability to
      agglutinate Gram-positive bacteria is stronger than that to Gram-negative
      bacteria whereas zITLN2 did not show such preference. This is probably due to the
      fact that recombinant zITLN1 could bind peptidoglycan (PGN) with a higher degree
      to lipopolysaccharide (LPS). Our results of zITLN1 provided new insight into the
      evolution and function of the intelectin family.

PMID- 30195916
TI  - Alterations of haemato-biochemical parameters pre and post-challenge with
      Aeromonas hydrophila and survival of Oreochromis mossambicus fed Moringa oleifera
      based diets.
AB  - This study investigated the extent of changes in haemato-biochemical and
      immunological parameters of O. mossambicus fed with M. oleifera-based diets pre
      and post-challenge with different concentrations of A. hydrophila. Moringa
      oleifera powdered leaves were added to five experimental diets at 0%, 3%, 6%, 9%
      and 12%, designated D1, D2, D3, D4 and D5, respectively. Each diet was randomly
      fed to triplicate groups of 45 fish (33.46 +/- 1.57 g) for 45 days. There were no
      significant differences (P > 0.05) in WG, FCR and SGR between treatments. There
      was an increase in WBC, RBC, HGB and HCT with increasing M. oleifera levels. No
      significant changes (P > 0.05) were observed in AST, ALT, ALP and LDH levels
      between treatments. After 45 days, fish from each treatment were injected with
      varying concentrations (0, 1 * 106 cfu, 1.5 * 106 cfu, 3 * 106 cfu and 4 * 106
      cfu ml-1) of Aeromonas hydrophila. There was a significant decline in RBC, HGB
      and HCT of fish in the D1-D3 compared to the D4 and D5 groups. There was an
      increase in AST, ALT, ALP and LDH in the D1-D3 groups while no significant
      changes (P > 0.05) were observed in the D4 and D5 groups between bacterial
      concentrations. Survival rate was lower in the D1-D3 compared to the D4 and D5
      groups, indicating that immunity was enhanced in fish fed with the highest M.
      oleifera inclusion levels. NBT and lysozyme activities were also lower in the D1
      D3 groups compared to the D4 and D5 groups. The enhancement of immunity is
      attributed to the presence of biologically active compounds with
      immunostimulatory properties. The phytochemistry of the M. oleifera revealed high
      levels of total polyphenol, total phenols, total flavonoids, carotenoids,
      vitamins C and E.

PMID- 30195917
TI  - A novel effector caspase (Caspase-3/7-1) involved in the regulation of immune
      homeostasis in Chinese mitten crab Eriocheir sinensis.
AB  - Caspases are a conserved family of cysteine proteases characterized by
      specificity for aspartic acid and play an essential role in cell apoptosis. In
      the present study, a novel effector caspase (designated as EsCaspase-3/7-1) was
      identified from Chinese mitten crab Eriocheir sinensis. The open reading frame of
      EsCaspase-3/7-1 cDNA was of 972 bp, encoding a polypeptide of 323 amino acids.
      EsCaspase-3/7-1 contained an N-terminal prodomain and a conservative C-terminal
      CASc domain, with the conserved active site "QACRG". The mRNA transcripts of
      EsCaspase-3/7-1 were constitutively expressed in all the examined tissues with
      high expression level in hemocytes, hepatopancreas and gill. The EsCaspase-3/7-1
      protein was mainly distributed in the cytoplasm of hemocytes. After Aeromonas
      hydrophila and lipopolysaccharide (LPS) stimulations, the mRNA expression level
      of EsCaspase-3/7-1 in hemocytes increased significantly. The mRNA expression
      level of EsCaspase-3/7-1 in hemocytes was significantly up-regulated after H2O2
      treatment in vitro. The recombinant EsCaspase-3/7-1 protein (rEsCaspase-3/7-1)
      was capable of hydrolyzing the substrate Ac-DEVD-pNA rather than Ac-YVAD-pNA and
      Ac-VEID-pNA in vitro, and exhibited binding activity to LPS. These results
      demonstrated that EsCaspase-3/7-1 might act as an LPS receptor, and play an
      important role in the regulation of immune homeostasis of E. sinensis.

PMID- 30195918
TI  - Autophagy participates in innate immune defense in lamprey.
AB  - Autophagy is a homeostatic process which degrades cytoplasmic constituents to
      maintain the balance of organs when they were challenged with nutrient stress. It
      also participates in cancer, neurodegenerative disorders, aging and innate immune
      defense. In order to reveal how autophagy participates in innate immune response
      when invertebrates evolved into vertebrates. Firstly, we performed a systematic
      analysis of Atg genes and found that they are highly conserved among lancelet,
      lamprey and zebrafish. Then, we observed autophagosomes upon starvation by TEM in
      lancelet, lamprey and zebrafish and found that the morphology of autophagosome is
      similar to that was observed in yeast and mammals. In addition, rapamycin can
      induce autophagy in lamprey leukocytes and the deficiency of human Beclin1
      protein can be rescued by lancelet and lamprey Beclin1 proteins. When lamprey
      leukocytes were treated with polyI:C and LPS, autophagy was induced. Moreover,
      when lamprey leukocytes were challenged with live E. coli, phagocytosis along
      with autophagy was triggered to degrade pathogenic bacteria. In all, our study
      here indicated that autophagy is highly conserved during evolution and plays a
      key role in innate defense when invertebrates evolved into vertebrates.

PMID- 30195919
TI  - General Family Functioning as a Predictor of Quality of Life in Parents of
      Children With Cancer.
AB  - PURPOSE: The diagnosis of cancer in a child brings about a crisis for the whole
      family. This study aimed to (1) determine family functioning and parents' quality
      of life in comparison with groups in relevant studies, (2) assess the correlation
      between dimensions of family functioning and parents' quality of life domains,
      and (3) explore the predictive role of general family functioning (GFF) for
      quality of life domains in a sample of families (mother-father as a dyad) of
      children with cancer. DESIGN AND METHODS: This is a cross-sectional study which
      was performed on 62 pairs of parents of children with cancer (n = 124). Data were
      collected using the Demographic-Clinical Information Questionnaire, validated
      Persian versions of the McMaster Family Assessment Device (FAD) and the World
      Health Organization's Quality of Life-BREF (WHOQOL-BRFF). The Canonical
      Correlation Analysis and the Generalized Estimating Equation (GEE) model were
      used for data analysis. RESULTS: All dimensions of the FAD were reported as
      unhealthy dimensions. Also, a poor quality of life was reported in all domains by
      parents. Most of the family functioning dimensions were correlated with quality
      of life domains. Consequently, after controlling for several demographic and
      clinical variables the GFF was the most important predictor of parents' quality
      of life and its domains. CONCLUSIONS: The GFF should be measured at the first
      meeting with a family of a child with cancer and during the follow-up meetings to
      help plan family empowerment interventions.

PMID- 30195920
TI  - Interferon-stimulated gene 60 (ISG60) constitutes a negative feedback loop in the
      downstream of TLR3 signaling in hCMEC/D3 cells.
AB  - Brain capillary endothelial cells are the component of blood brain barrier, and
      the first line of defense against viruses invading into brain. We demonstrate
      that treatment of hCMEC/D3 cells, a human brain capillary endothelial cell line,
      with a Toll-like receptor 3 (TLR3) agonist polyinosinic-polycytidylic acid (poly
      IC) induces the expression of interferon (IFN)-stimulated gene 60 (ISG60), and
      this reaction was mediated by IFN-beta. Knockdown of ISG60 increased the poly IC
      induced expression of IFN-beta and an IFN-beta-inducible chemokine CXCL10. This
      indicates that ISG60 constitutes a negative feedback loop in the downstream of
      TLR3/IFN-beta. ISG60 in brain capillary endothelial cells may contribute to
      prevent excess immune reactions associated with viral infections.

PMID- 30195921
TI  - Psychophysiological and self-reported responses in individuals with
      methamphetamine use disorder exposed to emotional video stimuli.
AB  - Individuals with methamphetamine use disorder (MUD) exhibit irritability and
      compulsive emotional responses, yet the relevant study is scarce. The
      characteristic of their positive and negative emotional responses can provide
      effective targets for the clinical intervention. In this study, we compared the
      emotional responses of 60 participants with MUD and 30 healthy participants to
      visual stimuli. They watched four types of video to elicit anger, fear,
      amusement, and joy emotional responses. The self-report of emotional responses
      (i.e., arousal, valence, and proximity), skin conductance level, and startle
      response were measured. Comparing to the healthy controls, the methamphetamine
      group's subjective arousal level of fear is significantly lower (t = 3.763, p <
      .01); the skin conductance level of joy is significantly higher (t = 2.086, p <
      .05), and the level of anger is marginal significantly higher (t = 1.984, p =
      .05); the startle response level of anger (t = 2.069, p < .05) and joy (t =
      2.406, p < .05) is significantly higher. The methamphetamine group exhibited an
      enhanced emotion response to anger and a decreased response to joy which may
      indicate the emotion dysregulation problem caused by drug. These results provide
      effective targets for clinical intervention in treating patients of MUD with
      emotion dysregulation problems.

PMID- 30195922
TI  - The Intestinal Stem Cell Niche: Homeostasis and Adaptations.
AB  - The intestinal epithelium is a rapidly renewing cellular compartment. This
      constant regeneration is a hallmark of intestinal homeostasis and requires a
      tightly regulated balance between intestinal stem cell (ISC) proliferation and
      differentiation. Since intestinal epithelial cells directly contact pathogenic
      environmental factors that continuously challenge their integrity, ISCs must also
      actively divide to facilitate regeneration and repair. Understanding niche
      adaptations that maintain ISC activity during homeostatic renewal and injury
      induced intestinal regeneration is therefore a major and ongoing focus for stem
      cell biology. Here, we review recent concepts and propose an active
      interconversion of the ISC niche between homeostasis and injury-adaptive states
      that is superimposed upon an equally dynamic equilibrium between active and
      reserve ISC populations.

PMID- 30195923
TI  - Identification of an alternative translation initiation site in the sequence of
      the commonly used Glutathione S-Transferase tag.
AB  - A large number of proteins are expressed in fusion with a tag to perform their
      purification. Glutathione-S-Transferase (GST) is a widely used tag to achieve
      passenger protein purification. Accordingly, commonly used commercial expression
      vectors contain the coding sequence of GST in order to express fusion proteins.
      However, fusion proteins are sometimes expressed in a truncated form that may
      result from an incomplete synthesis, proteolytic cleavage or the presence of a
      functional alternative translation initiation site. In particular, a truncated as
      well as a full-length fusion protein were observed when expressing RGS9-1 Anchor
      Protein without its C-terminal segment (bR9AP) in fusion with GST. Moreover, this
      truncated protein was found to be purified together with the full-length fusion
      protein. Here, we identified for the first time an alternative translation
      initiation site within the sequence of GST that likely becomes accessible for
      translation only when it is fused with a passenger protein. Indeed,
      bioinformatics analyses suggest that the secondary structure of the mRNA of the
      GST-bR9AP fusion protein is different from that of GST alone, which likely allows
      accessibility of an alternative Shine-Dalgarno sequence coupled with an
      additional initiation codon within the sequence of GST. The functionality of this
      alternative translation initiation site was confirmed by site-directed
      mutagenesis, which resulted in the absence of a truncated fusion protein and,
      consequently, only a purified full-length fusion protein. This is an extremely
      important finding in view of the wide use of GST as a purification and solubility
      enhancing tag.

PMID- 30195924
TI  - Administration of chitosan-tripolyphosphate-DNA nanoparticles to knockdown
      glutamate dehydrogenase expression impairs transdeamination and gluconeogenesis
      in the liver.
AB  - Glutamate dehydrogenase (GDH) plays a major role in amino acid catabolism. To
      increase the current knowledge of GDH function, we analysed the effect of GDH
      silencing on liver intermediary metabolism from gilthead sea bream (Sparus
      aurata). Sequencing of GDH cDNA from S. aurata revealed high homology with its
      vertebrate orthologues and allowed us to design short hairpin RNAs (shRNAs) to
      knockdown GDH expression. Following validation of shRNA-dependent downregulation
      of S. aurata GDH in vitro, chitosan-tripolyphosphate (TPP) nanoparticles
      complexed with a plasmid encoding a selected shRNA (pCpG-sh2GDH) were produced to
      address the effect of GDH silencing on S. aurata liver metabolism. Seventy-two
      hours following intraperitoneal administration of chitosan-TPP-pCpG-sh2GDH, GDH
      mRNA levels and immunodetectable protein decreased in the liver, leading to
      reduced GDH activity in both oxidative and reductive reactions to about 53-55 %
      of control values. GDH silencing decreased glutamate, glutamine and aspartate
      aminotransferase activity, while increased 2-oxoglutarate content, 2-oxoglutarate
      dehydrogenase activity and 6-phosphofructo-1-kinase/fructose-1,6-bisphosphatase
      activity ratio. Our findings show for the first time that GDH silencing reduces
      transdeamination and gluconeogenesis in the liver, hindering the use of amino
      acids as gluconeogenic substrates and enabling protein sparing and metabolisation
      of dietary carbohydrates, which would reduce environmental impact and production
      costs of aquaculture.

PMID- 30195925
TI  - High-Flow Nasal Cannulae. The Quest for the Holy Grail in the Critical
      Respiratory Patient?

PMID- 30195926
TI  - Determining the impact of pre-radiation treatment verification simulation/dry run
      by analyzing intradepartmental reported incidents and surveying staff and
      patients.
AB  - PURPOSE: Error identification in radiation therapy is critical to maintain a safe
      and efficient therapeutic environment. A verification simulation (VS; also called
      a dry run for patient information) provides a dedicated time prior to treatment
      to duplicate steps of patient setup, imaging, and treatment process as a final
      quality assurance step. Through the use of surveys and analysis of reported
      incidents, we sought to determine the value of a VS before initiating patient
      treatment. METHODS AND MATERIALS: In November 2014, a VS was instituted across
      our network of 11 radiation oncology clinics. A comparison of the incident rate
      reported through our departmental incident learning system (ILS) was made between
      a non-VS group (965 patients who were treated in the 18 months prior to
      instituting the VS) and a VS group (984 patients who were treated over 18 months
      with the VS policy in place). From August to December 2016, surveys were
      completed by 211 patients and 55 physicians, nurses, and therapists detailing
      their perspectives on the VS. RESULTS: There were 28 incidents (2.9%) in the non
      VS group compared with 18 incidents (1.8%) in the VS group (P = .03). In the VS
      group, more incidents were detected before the day of treatment (P = .03) and
      fewer incidents on the day of treatment (P = .02). In addition, a trend toward
      fewer incidents after treatment started (P = .09) was observed. Patient surveys
      indicated that 99.5% of patients were informed of the VS, 83% reported decreased
      anxiety during treatment, and 5% indicated concerns about delaying treatment. The
      majority of staff members (67%) were satisfied with the VS. CONCLUSIONS: A VS
      helps identify and correct incidents before the administration of radiation
      therapy and reduces patient anxiety.

PMID- 30195927
TI  - Using smaller-than-standard radiation treatment margins does not change survival
      outcomes in patients with high-grade gliomas.
AB  - PURPOSE: The number of studies that evaluate treatment margins for high grade
      gliomas (HGG) are limited. We hypothesize that patients with HGG who are treated
      with a gross tumor volume (GTV) to planning tumor volume (PTV) expansion of <=1
      cm will have progression-free survival (PFS) and overall survival (OS) rates
      similar to those treated in accordance with standard protocols by the Radiation
      Therapy Oncology Group or European Organisation for Research and Treatment of
      Cancer. Furthermore, the PFS and OS of subgroups within the study population will
      have equivalent survival outcomes with GTV1-to-PTV1 margins of 1.0 cm and 0.4 cm.
      METHODS AND MATERIALS: Treatment plans and outcomes for patients with
      pathologically confirmed HGG were analyzed (n = 267). Survival (PFS and OS) was
      calculated from the time of the first radiation treatment and a chi2 test or
      Fisher exact test was used to calculate the associations between margin size and
      patient characteristics. Survival was estimated using Kaplan-Meier and compared
      using the log-rank test. All analyses were performed on the univariate level.
      RESULTS: The median PFS and OS times were 10.6 and 19.1 months, respectively. By
      disease, the median PFS and OS times were 8.6 and 16.1 months for glioblastoma
      and 26.7 and 52.5 months for anaplastic glioma. The median follow-up time was
      18.3 months. The treatment margin had no effect on outcome and the 1.0 cm GTV1
      PTV1 margin subgroup (n = 212) showed median PFS and OS times of 10.7 and 19.1
      months, respectively, and the 0.4 cm margin subgroup (n = 55) 10.2 and 19.3
      months, respectively. In comparison with the standard treatment with 2 cm to 3 cm
      margins, there was not a significant difference in outcomes. CONCLUSIONS: There
      is no apparent difference in survival when utilizing smaller versus larger
      margins as defined by the guidelines of the Radiation Therapy Oncology Group and
      European Organisation for Research and Treatment of Cancer. Although there
      remains no class I evidence that outcomes after treatment with smaller margins
      are identical to those after treatment with larger margins, this large series
      with long-term follow up suggests that a reduction of the margins is safe and
      further investigation is warranted.

PMID- 30195928
TI  - Spatially-resolved mineral identification and depth profiling on chondrules from
      the primitive chondrite Elephant Moraine 14017 with confocal Raman spectroscopy.
AB  - Confocal Raman spectroscopy is effective in unveiling structures of minerals
      without destruction from surface to certain depth. In this study, we introduce an
      application of confocal Raman spectroscopy on minerals in a primitive chondritic
      meteorite. The experimental lateral resolution on silicate minerals in this study
      is ~1.0 MUm. Raman spectrum of mesostasis in a named "Tear Drop" chondrule, a
      spherule object from a primitive chondrite, of Elephant Moraine 14017 (EET 14017)
      shows a broad feature indicating amorphous phase, which is a common
      characteristic of primitive chondrule mesostasis. Weak intensities of 825 and 858
      cm-1 peaks were observed in the glassy mesostasis, probably originated from
      olivine below the surface. A plagioclase-rich chondrule (PRC-1) of EET 14017 was
      investigated with Raman spectroscopy, which contains two different occurrences of
      plagioclase: lath-shaped and interstitial grains. The strong intensity of 488 and
      505 cm-1 (plagioclase) and weak intensity of 461 cm-1 band were observed on the
      lath-shaped plagioclase. The weak 461 cm-1 peak from the plagioclase is probably
      from the subsurface quartz. Raman spectrum of interstital plagioclase in PRC-1
      shows 488 and 505 cm-1 bands and weak pyroxene bands. Depth profiling conducted
      on the interstitial plagioclase clearly shows that pyroxene exists below the
      surface. High-lateral resolution and well-resolved depth profiling with the
      confocal Raman spectroscopy allows us to identify tiny grains and investigate
      hidden phases underneath the surface without destruction of extraterrestrial
      materials.

PMID- 30195929
TI  - Fluorescence spectroscopy-based study of balanced transport of charge carriers in
      hot-air-annealed perovskites.
AB  - Using fluorescence spectroscopy, we investigate the transport of charge carriers
      in (p-i-n) planar perovskite (CH3NH3PbI3-xClx) solar cells with the structure
      ITO/PEDOT:PSS/perovskites/PCBM/Ca/Al, in which the perovskite morphology is
      optimized by moisture pretreatment (MPT) and the hot-air-annealing process
      (HAAP). After annealing with hot air, the electron transport time of the
      perovskites is shortened by a factor of 3.6 (from 28.8 to 7.9 ns), eventually
      leading to balanced transport of electrons and holes (characterized by the
      fluorescence-decay time constants of 7.9 and 7.6 ns, respectively). These results
      are in good agreement with the observed increase in the photovoltaic conversion
      efficiency.

PMID- 30195930
TI  - A new symbiotic nanoarchaeote (Candidatus Nanoclepta minutus) and its host
      (Zestosphaera tikiterensis gen. nov., sp. nov.) from a New Zealand hot spring.
AB  - Three thermophilic Nanoarchaeota-Crenarchaeota symbiotic systems have been
      described. We obtained another stable anaerobic enrichment culture at 80 degrees
      C, pH 6.0 from a New Zealand hot spring. The nanoarchaeote (Ncl-1) and its host
      (NZ3T) were isolated in co-culture and their genomes assembled. The small
      (~200nm) flagellated cocci were often attached to larger cocci. Based on 16S rRNA
      gene similarity (88.4%) and average amino acid identity (52%), Ncl-1 is closely
      related to Candidatus Nanopusillus acidilobi. Their genomes both encode for
      archaeal flagella and partial glycolysis and gluconeogenesis pathways, but lack
      ATP synthase genes. Like Nanoarchaeum equitans, Ncl-1 has a CRISPR-Cas system.
      Ncl-1 also relies on its crenarchaeotal host for most of its biosynthetic needs.
      The host NZ3T was isolated and grows on proteinaceous substrates but not on
      sugars, alcohols, or fatty acids. NZ3T requires thiosulfate and grows best at 82
      degrees C, pH 6.0. NZ3T is most closely related to the Desulfurococcaceae,
      Ignisphaera aggregans (~92% 16S rRNA gene sequence similarity, 45% AAI). Based on
      phylogenetic, physiological and genomic data, Ncl-1 and NZ3T represent novel
      genera in the Nanoarchaeota and the Desulfurococcaceae, respectively, with the
      proposed names Candidatus Nanoclepta minutus and Zestosphaera tikiterensis gen.
      nov., sp. nov., type strain NZ3T (=DSMZ 107634T=OCM 1213T).

PMID- 30195931
TI  - Autism spectrum disorder, social communication difficulties, and developmental
      comorbidities in Sturge-Weber syndrome.
AB  - Sturge-Weber syndrome (SWS) is a neurocutaneous disorder characterized by the
      combination of a facial naevus flammeus and pial angioma, often associated with
      learning difficulties and/or epilepsy. Here, we report on the neuropsychological
      characteristics of a cohort of 92 children with SWS seen at a national referral
      center between 2002 and 2015. Almost a quarter (24%) had a diagnosis of autism
      spectrum disorder (ASD), with 45% overall having evidence of social communication
      difficulties (SCD). Autism spectrum disorder was more commonly seen in those
      individuals with bilateral angioma (p = 0.021). Significant behavioral
      difficulties were reported in 50% while 26% had difficulties with sleep.
      Difficulties with social communication, behavior, and sleep were closely
      associated with one another. They were not, however, significantly associated
      with markers of epilepsy severity and were noted to occur even in children
      without epilepsy. The prevalence of ASD/SCD, sleep difficulties, and behavioral
      disorders seen in SWS is high and reflects the complex needs of this group.

PMID- 30195932
TI  - Electrophysiological assessment methodology of sensory processing dysfunction in
      schizophrenia and dementia of the Alzheimer type.
AB  - Schizophrenia and Alzheimer's disease impacts on various sensory processings are
      extensively reviewed in the present publication. This article describes aspects
      of a research project whose aim is to delineate the neurobiology that may
      underlie Social Withdrawal in Alzheimer's disease, Schizophrenia and Major
      Depression. This is a European-funded IMI 2 project, identified as PRISM
      (Psychiatric Ratings using Intermediate Stratified Markers). This paper focuses
      specifically on the selected electrophysiological paradigms chosen based on a
      comprehensive review of all relevant literature and practical constraints. The
      choice of the electrophysiological biomarkers were fundamentality based their
      metrics and capacity to discriminate between populations. The selected
      electrophysiological paradigms are resting state EEG, auditory mismatch
      negativity, auditory and visual based oddball paradigms, facial emotion
      processing ERP's and auditory steady-state response. The primary objective is to
      study the effect of social withdrawal on various biomarkers and endophenotypes
      found altered in the target populations. This has never been studied in
      relationship to social withdrawal, an important component of CNS diseases.

PMID- 30195933
TI  - Targeting the gut microbiota to influence brain development and function in early
      life.
AB  - In the first 2-3 years of life, the gut microbiota of infants quickly becomes
      diverse and rich. Disruptions in the evolving gut microbiota during this critical
      developmental period can impact brain development. Communication between the
      microbiota, gut and brain is driven by hormonal and neural regulation, as well as
      immune and metabolic pathways, however, our understanding of how the parallel
      developments that may underlie this communication are limited. In this paper, we
      review the known associations between the gut microbiota and brain development
      and brain function in early life, speculate on the potential mechanisms involved
      in this complex relationship and describe how nutritional intervention can
      further modulate the microbiota and, ultimately, brain development and function.

PMID- 30195934
TI  - Review: The role of computational simulation in understanding the postoperative
      sinonasal environment.
AB  - Nasal surgery improves symptoms in a majority of patients for whom medical
      treatment has failed. In rhinosinusitis patients, endoscopic sinus surgery aims
      to alleviate obstruction and re-establish mucociliary clearance. Surgery alters
      the structure-function relationship within the nasal passage, which is difficult
      to assess clinically. Computational modelling has been used to investigate this
      relationship by simulating air flow and environmental variables inside realistic
      three-dimensional models of the human nasal airway but many questions remain
      unanswered and need further investigation. The application of computational
      models to improve pre-surgical planning and post-surgical treatment may not be
      currently possible due to the absence of knowledge correlating the model
      predicted parameters to physiological variables. Links between these parameters
      to patient outcomes are yet to be established. This article reviews the recent
      application of computational modelling to understand the nasal structure-function
      relationship following surgery in patients with sinusitis and nasal obstruction.

PMID- 30195935
TI  - Is there an impact of cervical plating on the development of adjacent segment
      degeneration following Smith-Robinson procedure? A magnetic resonance imaging
      study of 84 patients with a 24-year follow-up.
AB  - BACKGROUND CONTEXT: Anterior cervical discectomy and fusion (ACDF) without and
      with cervical plating (ACDF+CP) are accepted surgical techniques for the
      treatment of degenerative cervical disc disorders. The effect of CP on the
      development of adjacent segment degeneration (ASD) remains unclear. PURPOSE: To
      assess whether CP accelerates the degeneration of the adjacent and adjoining
      segments. STUDY DESIGN/SETTING: This is an imaging cohort study. PATIENT SAMPLE:
      Retrospectively, a total of 84 patients who underwent ACDF or ACDF+CP were
      identified. At final follow-up, an MRI was performed and evaluated in this study.
      MATERIALS AND METHODS: An MRI of 84 patients who underwent ACDF (46 patients) and
      ACDF+PS (38 patients) was performed. The mean follow-up was 24years (17-45
      years). None of the patients had a repeat procedure in the cervical spine. The
      grade of degeneration of the segments adjacent and adjoining to the fusion was
      assessed via a five-step grading system (segmental degeneration index, or SDI)
      that includes disc signal intensity, anterior and posterior disc protrusion,
      narrowing of the disc space, and foraminal stenosis. Furthermore, the disc height
      (DH) and sagittal segmental angle (SSA) of fused segments were measured. RESULTS:
      A significantly (p<.001) greater SDI was identified at the caudal adjacent
      segment following ACDF compared to ACDF+CP. No other significant differences were
      identified in patients following ACDF and ACDF+CP. Between 50% and 96% of all
      segments showed severe degenerative changes according to SDI. There was no
      significant difference in DH between the patients following ACDF and ACDF+CP. The
      SSA in patients who underwent ACDF+CP was significantly greater than in the ACDF
      patients (p=.002). CONCLUSIONS: In this cohort of patients, cervical plating had
      no significant impact on segmental degeneration and decrease of DH in the
      adjacent and adjoining segments. ACDF+CP seem to preserve the lordotic alignment
      more with respect to the SSA than ACDF.

PMID- 30195936
TI  - Computational Investigation of Ripple Dynamics in Biofilms in Flowing Systems.
AB  - Biofilms are collections of microorganisms that aggregate using a self-produced
      matrix of extracellular polymeric substance. It has been broadly demonstrated
      that many microbial infections in the body, including dental plaque, involve
      biofilms. While studying experimental models of biofilms relevant to mechanical
      removal of oral biofilms, distinct ripple patterns have been observed. In this
      work, we describe a multiphase model used to approximate the dynamics of the
      biofilm removal process. We show that the fully nonlinear model provides a better
      representation of the experimental data than the linear stability analysis. In
      particular, we show that the full model more accurately reflects the relationship
      between the apparent wavelength and the external forcing velocities, especially
      at mid-to-low velocities at which the linear theory neglects important
      interactions. Finally, the model provides a framework by which the removal
      process (presumably governed by highly nonlinear behavior) can be studied.

PMID- 30195937
TI  - Lipid-Mediated Interactions between the Antimicrobial Peptides Magainin 2 and
      PGLa in Bilayers.
AB  - A synergistic enhancement of activities has been described for the amphipathic
      cationic antimicrobial peptides magainin 2 and PGLa when tested in antimicrobial
      assays or in biophysical experiments using model membranes. In the presence of
      magainin 2, PGLa changes from an in-planar alignment parallel to the membrane
      surface to a more transmembrane orientation when investigated in membranes made
      from fully saturated PC or PC/PG, but not when one of the fatty acyl chains is
      unsaturated. Such lipid-mediated changes in the membrane topology of polypeptide
      domains could provide an interesting mechanism for the regulation of membrane
      proteins. Here we investigated the PGLa topology in a wide variety of membranes
      made of saturated or unsaturated PE, PC, and/or PG using 15N solid-state NMR
      spectroscopy. In contrast to predictions made by previous models the data show
      that membrane curvature has only a minor effect on PGLa realignment. Furthermore,
      using 2H solid-state NMR spectroscopy of deuterated phospholipid fatty acyl
      chains the order parameters of the lipids were investigated in the presence of
      PGLa, magainin, or equimolar peptide mixtures. Both peptides cause a pronounced
      decrease in the order parameters when oriented parallel to the membrane surface,
      an effect that reverts when PGLa flips into transmembrane alignments. Taken
      together, these data are suggestive that the magainin-induced disordering of
      fatty acyl chains provides an important driving force for PGLa realignment.

PMID- 30195938
TI  - Precise Binding of Tropomyosin on Actin Involves Sequence-Dependent Variance in
      Coiled-Coil Twisting.
AB  - Often considered an archetypal dimeric coiled coil, tropomyosin nonetheless
      exhibits distinctive "noncanonical" core residues located at the hydrophobic
      interface between its component alpha-helices. Notably, a charged aspartate,
      D137, takes the place of nonpolar residues otherwise present. Much speculation
      has been offered to rationalize potential local coiled-coil instability stemming
      from D137 and its effect on regulatory transitions of tropomyosin over actin
      filaments. Although experimental approaches such as electron cryomicroscopy
      reconstruction are optimal for defining average tropomyosin positions on actin
      filaments, to date, these methods have not captured the dynamics of tropomyosin
      residues clustered around position 137 or elsewhere. In contrast, computational
      biochemistry, involving molecular dynamics simulation, is a compelling choice to
      extend the understanding of local and global tropomyosin behavior on actin
      filaments at high resolution. Here, we report on molecular dynamics simulation of
      actin-free and actin-associated tropomyosin, showing noncanonical residue D137 as
      a locus for tropomyosin twist variation, with marked effects on actin-tropomyosin
      interactions. We conclude that D137-sponsored coiled-coil twisting is likely to
      optimize electrostatic side-chain contacts between tropomyosin and actin on the
      assembled thin filament, while offsetting disparities between tropomyosin
      pseudorepeat and actin subunit periodicities. We find that D137 has only minor
      local effects on tropomyosin coiled-coil flexibility, (i.e., on its flexural
      mobility). Indeed, D137-associated overtwisting may actually augment tropomyosin
      stiffness on actin filaments. Accordingly, such twisting-induced stiffness of
      tropomyosin is expected to enhance cooperative regulatory translocation of the
      tropomyosin cable over actin.

PMID- 30195939
TI  - Folding and Lipid Composition Determine Membrane Interaction of the Disordered
      Protein COR15A.
AB  - Plants from temperate climates, such as the model plant Arabidopsis thaliana, are
      challenged with seasonal low temperatures that lead to increased freezing
      tolerance in fall in a process termed cold acclimation. Among other adaptations,
      this involves the accumulation of cold-regulated (COR) proteins, such as the
      intrinsically disordered chloroplast-localized protein COR15A. Together with its
      close homolog COR15B, it stabilizes chloroplast membranes during freezing. COR15A
      folds into amphipathic alpha-helices in the presence of high concentrations of
      low-molecular-mass crowders or upon dehydration. Under these conditions, the
      (partially) folded protein binds peripherally to membranes. In our study, we have
      used coarse-grained molecular dynamics simulations to elucidate the details of
      COR15A-membrane binding and its effects on membrane structure and dynamics.
      Simulation results indicate that at least partial folding of COR15A and the
      presence of highly unsaturated galactolipids in the membranes are necessary for
      efficient membrane binding. The bound protein is stabilized on the membrane by
      interactions of charged and polar amino acids with galactolipid headgroups and by
      interactions of hydrophobic amino acids with the upper part of the fatty acyl
      chains. Experimentally, the presence of liposomes made from a mixture of lipids
      mimicking chloroplast membranes induces additional folding in COR15A under
      conditions of partial dehydration, in agreement with the simulation results.

PMID- 30195940
TI  - Multiplex Single-Molecule DNA Barcoding Using an Oligonucleotide Ligation Assay.
AB  - Detection of specific nucleic acid sequences is invaluable in biological studies
      such as genetic disease diagnostics and genome profiling. Here, we developed a
      highly sensitive and specific detection method that combines an advanced
      oligonucleotide ligation assay with multicolor single-molecule fluorescence. We
      demonstrated that under our experimental conditions, 7-nucleotide long DNA
      barcodes have the optimal short length to ascertain specificity while being long
      enough for sufficient ligation. Using four spectrally separated fluorophores to
      label DNA barcodes, we simultaneously distinguished four DNA target sequences
      differing by only a single nucleotide. Our single-molecule approach will allow
      for accurate identification of low-abundance molecules without the need for
      target DNA preamplification.

PMID- 30195941
TI  - Synchronization of Triggered Waves in Atrial Tissue.
AB  - When an atrial cell is paced rapidly, calcium (Ca) waves can form on the cell
      boundary and propagate to the cell interior. These waves are referred to as
      "triggered waves" because they are initiated by Ca influx from the L-type Ca
      channel and occur during the action potential. However, the consequences of
      triggered waves in atrial tissue are not known. Here, we develop a
      phenomenological model of Ca cycling in atrial myocytes that accounts for the
      formation of triggered waves. Using this model, we show that a fundamental
      requirement for triggered waves to induce abnormal electrical activity in tissue
      is that these waves must be synchronized over large populations of cells. This is
      partly because triggered waves induce a long action potential duration (APD)
      followed by a short APD. Thus, if these events are not synchronized between
      cells, then they will on average cancel and have minimal effects on the APD in
      tissue. Using our computational model, we identify two distinct mechanisms for
      triggered wave synchronization. The first relies on cycle length (CL)
      variability, which can prolong the CL at a given beat. In cardiac tissue, we show
      that CL prolongation leads to a substantial amplification of APD because of the
      synchronization of triggered waves. A second synchronization mechanism applies in
      a parameter regime in which the cell exhibits stochastic alternans in which a
      triggered wave fires, on average, only every other beat. In this scenario, we
      identify a slow synchronization mechanism that relies on the bidirectional
      feedback between the APD in tissue and triggered wave initiation. On large
      cables, this synchronization mechanism leads to spatially discordant APD
      alternans with spatial variations on a scale of hundreds of cells. We argue that
      these spatial patterns can potentially serve as an arrhythmogenic substrate for
      the initiation of atrial fibrillation.

PMID- 30195942
TI  - Functional haplotypes of ARID4A affect promoter activity and semen quality of
      bulls.
AB  - The AT-rich interaction domain 4 A (ARID4A) has an important role in regulating
      Sertoli cell function and male fertility. Its molecular mechanisms, however,
      remain largely unknown. In this study, two single nucleotide polymorphisms (SNPs)
      (g.53 G > T, ss 1966531596, and g.826 G > A, rs 210809648) were identified in the
      promoter region of ARID4A in 215 Chinese Holstein bulls using polymerase chain
      reaction (PCR)-restriction fragment length polymorphism and created restriction
      site-PCR. Results revealed that bulls with g.53 G > T-GG and g.826 G > A-G G
      genotype exhibited higher sperm deformity rate than those with g.53 G > T-TT and
      g.826 G > A-AA genotype (P <  0.01). Furthermore, three haplotypes (H1 (GG), H3
      (TG), H4 (TA)) and six haplotype combinations (H1H1, H1H3, H1H4, H3H3, H3H4,
      H4H4) were obtained. The bulls with H4H4 exhibited lower sperm deformity rate
      than those with H1H1 and H1H3 (P <  0.05). In addition, results of bioinformatics
      analysis revealed that ARID4A has two promoters and that two SNPs of ARID4A are
      located in transcription factor binding sites. Compared with g.53 G > T-G and
      g.826 G > A-G allele, there was a greater fluorescence intensity in g.53 G > T-T
      and g.826 G > A-A allele by transient transfection in MLTC-1 cells and the
      luciferase report assay. qRT-PCR indicated the ARID4A expression was greater in
      bull spermatozoa with H4H4 haplotype combination than those with H1H1 haplotype
      combination (P < 0.05). Results of the present study indicate that g.53 G > T and
      g.826 G > A are functional mutations that are involved in regulation of ARID4A
      gene expression by affecting promoter activity and thus semen quality of Chinese
      Holstein bulls.

PMID- 30195943
TI  - Uterine inflammation and fertility of beef cows subjected to timed AI at
      different days postpartum.
AB  - The aim of this study was to evaluate the uterine health and fertility of
      postpartum beef cows subjected to timed AI (TAI) protocols at different days from
      calving. Lactating Nelore cows (Bos indicus; n = 244) were used in this study.
      The TAI protocols were initiated between 20 and 60 days postpartum (DPP). Cows
      were subjected to an estradiol-progesterone based TAI protocol. The cows were
      divided into three groups according to the days postpartum at the time the
      hormonal treatment was initiated: 1) Early (n = 64), cows between 20 and 30 DPP;
      2) Middle (n = 115), cows between 31 and 45 DPP; and 3) Late (n = 65), cows
      between 46 and 60 DPP. At Day 0 of the protocol, endometrial cytobrush samples
      were collected. Slides for polymorphonuclear (PMN) cell counting were prepared
      and cytobrush was used for RNA extraction and analysis of relative abundance of
      il1, il6, il8, and tnf mRNA. Cows from the Early group had less (P < 0.05)
      pregnancies per AI (P/AI) than cows from Middle and Late groups; 29.7% (19/64),
      45.2% (52/115), and 52.31% (34/65), respectively. Accordingly, the Early group
      had a greater (P < 0.05) proportion of PMN cells in the uterus than Middle and
      Late groups; 9.0%, 3.8%, and 2.2%, respectively. Relative abundances of il1 and
      il8 mRNA were greater (P < 0.05) in the Early group than Middle and Late groups.
      These results indicate that beef cows subjected to TAI protocols early postpartum
      (< 30 DPP) are less likely to become pregnant, which is associated with increased
      inflammation and relative abundance of mRNA for the proinflammatory cytokines il1
      and il8.

PMID- 30195944
TI  - Relationship of organic mineral supplementation and spermatozoa/white blood cells
      mRNA in goats.
AB  - The antioxidant properties and the protective role of organic zinc (Zn) and
      copper (Cu) in white blood cells (WBCs) and spermatozoa were analyzed through
      quantification of superoxide dismutase 1 (SOD1), catalase (CAT), glutathione
      peroxidase 4 (GPx4) and nuclear factor erythroid 2-like 2 (NFE2L2) and
      correlations were determined with sperm functional characteristics in Osmanabadi
      bucks. Bucks (aged 5 months; n = 40) were divided into ten groups, and the
      dietary treatments comprised of a control and nine treatment groups as follows:
      organic Zn as Zn 20, Zn 40 and Zn 60, organic Cu as Cu 12.5, Cu 25, Cu 37.5 and
      combined organic Zn and Cu as Zn 20+Cu 12.5, Zn 40+Cu 25, Zn 60+Cu 37.5,
      respectively per kg dry matter for a period of 8 months. The blood (120 and 240
      days) and semen (240 days: 40 * 4 = 160) samples were collected from 40 bucks. In
      WBCs: the relative abundance of mRNA for SOD1, CAT, GPx4, NFE2L2 was greater (P <
      0.05) in (120 and 240 days) in majority of the mineral supplemented animals. In
      spermatozoa: the relative abundance of SOD1, NFE2L2, GPx4 and CAT mRNA was
      greater (P < 0.05) in selected treatment groups. The abundance of SOD1 mRNA in
      WBCs was positively correlated (P <  0.05) with sperm mass motility (r = 0.692, P
      = 0.027). The abundance of GPx4 mRNA was negatively correlated (P <  0.05) with
      type A sperm (straightness; STR) > 85% and amplitude of lateral head displacement
      (ALH) > 2.5 MUm/ s) (r = -0.711, P = 0.021) and (P <  0.05) positively correlated
      with sperm viability (r = 0.669, P = 0.035). Organic Zn and Cu supplementation
      was associated with an increase in the expression of antioxidant defense enzyme
      genes in bucks.

PMID- 30195945
TI  - Molecular imaging of coronary inflammation.
AB  - Coronary inflammation is related to atherosclerotic disease and, less frequently,
      systemic vasculitis. Regardless of the etiology, coronary inflammation is
      associated with adverse cardiac events. Molecular imaging with 18F
      fluorodeoxyglucose (FDG) positron emission tomography (PET/CT) allows in vivo
      assessment of coronary inflammation and evaluation of response to therapy. The
      aim of this review is to give an update on the recent development of FDG-PET/CT,
      discuss the potential roles of coronary inflammation imaging, review the
      limitations of FDG-PET/CT imaging, and give an overview of the new tracers
      available for PET/CT plaque imaging.

PMID- 30195946
TI  - Effect of Intranasal Vasoconstrictors on Blood Pressure: A Randomized, Double
      Blind, Placebo-Controlled Trial.
AB  - BACKGROUND: Treatment for epistaxis includes application of intranasal
      vasoconstrictors. These medications have a precaution against use in patients
      with hypertension. Given that many patients who present with epistaxis are
      hypertensive, these warnings are commonly overridden by clinical necessity.
      OBJECTIVE: Our aim was to determine the effects of intranasal vasoconstrictors on
      blood pressure. METHODS: We conducted a single-center, randomized, double-blind,
      placebo-controlled trial from November 2014 through July 2016. Adult patients
      being discharged from the emergency department (ED) at Mayo Clinic (Rochester,
      Minnesota) were recruited. Patients were ineligible if they had a
      contraindication to study medications, had a history of hypertension, were
      currently taking antihypertensive or antidysrhythmic medications, or had nasal
      abnormalities, such as epistaxis. Subjects were randomized to one of four study
      arms (phenylephrine 0.25%; oxymetazoline 0.05%; lidocaine 1% with epinephrine
      1:100,000; or bacteriostatic 0.9% sodium chloride [saline]). Blood pressure and
      heart rate were measured every 5 min for 30 min. RESULTS: Sixty-eight patients
      were enrolled in the study; of these, 63 patients completed the study
      (oxymetazoline, n = 15; phenylephrine, n = 20; lidocaine with epinephrine, n =
      11; saline, n = 17). We did not observe any significant differences in mean
      arterial pressure over time between phenylephrine and saline, oxymetazoline and
      saline, or lidocaine with epinephrine and saline. The mean greatest increases
      from baseline in mean arterial pressure, systolic and diastolic blood pressure,
      and heart rate for each treatment group were also not significantly different
      from the saline group. CONCLUSIONS: Intranasal vasoconstrictors did not
      significantly increase blood pressure in patients without a history of
      hypertension. Our findings reinforce the practice of administering these
      medications to patients who present to the ED with epistaxis, regardless of high
      blood pressure.

PMID- 30195947
TI  - A comparative fMRI meta-analysis of altruistic and strategic decisions to give.
AB  - The decision to share resources is fundamental for cohesive societies. Humans can
      be motivated to give for many reasons. Some generosity incurs a definite cost,
      with no extrinsic reward to the act, but instead provides intrinsic satisfaction
      (labelled here as 'altruistic' giving). Other giving behaviours are done with the
      prospect of improving one's own situation via reciprocity, reputation, or public
      good (labelled here as 'strategic' giving). These contexts differ in the source,
      certainty, and timing of rewards as well as the inferences made about others'
      mental states. We executed a combined statistical map and coordinate-based fMRI
      meta-analysis of decisions to give (36 studies, 1150 participants). Methods
      included a novel approach for accommodating variable signal dropout between
      studies in meta-analysis. Results reveal consistent, cross-paradigm neural
      correlates of each decision type, commonalities, and informative differences.
      Relative to being selfish, altruistic and strategic giving activate overlapping
      reward networks. However, strategic decisions showed greater activity in striatal
      regions than altruistic choices. Altruistic giving, more than strategic,
      activated subgenual anterior cingulate cortex (sgACC). Ventromedial prefrontal
      cortex (vmPFC) is consistently involved during generous decisions and processing
      across a posterior to anterior axis differentiates the altruistic/strategic
      context. Posterior vmPFC was preferentially recruited during altruistic
      decisions. Regions of the 'social brain' showed distinct patterns of activity
      between choice types, reflecting the different use of theory of mind in the two
      contexts. We provide the consistent neural correlates of decisions to give, and
      show that many will depend on the source of incentives.

PMID- 30195948
TI  - Time to revise classification of phyllodes tumors of breast? Results of a French
      multicentric study.
AB  - OBJECTIVE: To assess prognostic factors of recurrence of phyllodes tumors (PT) of
      the breast. METHODS: We performed a retrospective, multicentric cohort study,
      including all patients who underwent breast surgery for grade 1 (benign), 2
      (borderline) or 3 (malignant) PT between 2000 and 2016 in five tertiary
      University hospitals, diagnosed according to World Health Organisation
      classification. RESULTS: 230 patients were included: 144 (63%), 60 (26%) and 26
      (11%) with grade 1, 2 and 3 PT, respectively. Recurrence occurred in 10 (7%), 7
      (12%) and 5 (19%) patients with grade 1, 2 and 3 PT, respectively. In univariate
      analysis, moderate to severe nuclear stromal pleomorphism (HR 8.00 [95% CI: 1.65
      38.73], p < 0.009) was correlated with recurrence in all groups including grade 1
      (HR 14.3 [95% CI: 1.29-160], p = 0.031). In multivariate analysis, surgical
      margin >5 mm, (HR 0.20 [95% CI: 0.06-0.63], p = 0.013) were significantly
      correlated with less recurrence in all PT grades. For grade 1 PT, there was also
      significantly less recurrence with surgical margin >5 mm, (HR 0.09 [95% CI: 0.01
      0.85], p = 0.047) in multivariate analysis. CONCLUSION: The surgical margin
      should be at least 5 mm whatever the grade of PT. Moderate to severe nuclear
      stromal pleomorphism identified a subgroup of grade 1 PT with a higher rate of
      recurrence. This suggests that the WHO classification could be revised with the
      introduction of nuclear stromal pleomorphism to tailor PT management.

PMID- 30195949
TI  - The interplay between externalizing disorders polygenic risk scores and
      contextual factors on the development of marijuana use disorders.
AB  - Externalizing disorders have been extensively linked to substance use problems.
      However, less is known about whether genetic factors underpinning externalizing
      disorders and environmental features interact to predict substance use disorders
      (i.e., marijuana abuse and dependence) among urban African Americans. We examined
      whether polygenic risk scores (PRS) for conduct disorder (CD) and attention
      deficit hyperactivity disorder (ADHD) interacted with contextual factors (i.e.,
      parental monitoring, community disadvantage) to influence risk for marijuana use
      disorders in a sample of African American youth. Participants (N=1,050; 44.2%
      male) were initially recruited for an elementary school-based universal
      prevention trial in a Mid-Atlantic city and followed through age 20. Participants
      reported on their parental monitoring in sixth grade and whether they were
      diagnosed with marijuana abuse or dependence at age 20. Blood or saliva samples
      were genotyped using the Affymetrix 6.0 microarrays. The CD and ADHD PRS were
      created based on genome-wide association studies conducted by Dick et al. (2010)
      and Demontis et al. (2017), respectively. Community disadvantage was calculated
      based on census data when participants were in sixth grade. There was an
      interaction between the CD PRS and community disadvantage such that a higher CD
      PRS was associated with greater risk for a marijuana use disorder at higher
      levels of neighborhood disadvantage. This finding should be interpreted with
      caution owing to the number of significance tests performed. Implications for
      etiological models and future research directions are presented.

PMID- 30195950
TI  - Greater Tuberosity Decortication Decreases Load to Failure of All-Suture Anchor
      Constructs in Rotator Cuff Repair.
AB  - PURPOSE: To evaluate the effect of greater tuberosity decortication on ultimate
      load to failure and displacement after cyclic loading with an all-suture anchor.
      METHODS: A 2.9-mm all-suture anchor was evaluated in decorticated and
      nondecorticated greater tuberosities of 10 matched pairs of human cadaveric
      shoulders. Greater tuberosity decortication was performed to a mean depth of 1.7
      mm. Anchors were placed in the anterior, middle, and posterior tuberosity.
      Anchors were tested under cyclic loads followed by load-to-failure testing.
      Displacement after 20, 100, and 200 cycles and ultimate failure strength were
      determined. Clinical failure was defined as displacement greater than 5 mm during
      cyclic loading. RESULTS: After 20 and 100 cycles, there was no difference in mean
      displacement between the decorticated and nondecorticated cohorts (P = .139 and P
      = .127, respectively). The mean displacement after 200 cycles was greater in the
      decorticated cohort, although not significantly (3.4 vs 2.7 mm; P = .05). The
      mean ultimate load to failure was significantly lower in the decorticated cohort
      (314 vs 386 N, P = .049). There were 2 clinical failures in the decorticated
      specimens and 1 in the nondecorticated specimens. CONCLUSIONS: A minimal greater
      tuberosity decortication significantly decreases the ultimate load to failure of
      an all-suture anchor. However, decreased biomechanical strength may not
      necessitate actual clinical failure. CLINICAL RELEVANCE: A decrease in ultimate
      load to failure could increase the risk of catastrophic postoperative anchor
      failure. However, while this decrease in strength is statistically significant,
      the overall decrease in strength may not be sufficient in magnitude to translate
      to clinical failure.

PMID- 30195951
TI  - Bioelectric Silver-Zinc Dressing Equally Effective to Chlorhexidine in Reducing
      Skin Bacterial Load in Healthy Volunteers.
AB  - PURPOSE: The aim of the present study was to evaluate and compare the
      effectiveness of the silver-zinc bioelectric dressing as compared with skin
      preparation with 2% chlorhexidine or 4% chlorhexidine in reducing the bacterial
      count on the knee. METHODS: Three groups consisting of 48 healthy volunteers were
      included. Age range was 23 to 54 years old and 60% of participants were male.
      Each subject had 1 knee serve as the test and the contralateral as the control.
      The test site was prepared with either 2% chlorhexidine, 4% chlorhexidine, or a
      silver-zinc bioelectric dressing and after 24 hours skin cultures were taken and
      examined for bacterial growth. RESULTS: In the 2% chlorhexidine group 23 of 48
      unprepped knees had positive cultures, compared with 9 of 48 prepped knees (P =
      .003; risk reduction, 4.0 times). In the 4% chlorhexidine group 25 of 48
      unprepped knees had positive cultures, compared with 14 of 48 prepped knees (P =
      .027; risk reduction, 2.6 times). In the silver-zinc bioelectric dressing group
      29 of 48 unprepped knees had positive cultures, compared with 7 of 48 prepped
      knees (P < .001; risk reduction, 8.9 times). There was no difference in the
      positive skin culture rate between the 3 methods. CONCLUSIONS: Application of the
      silver-zinc bioelectric dressing was equally effective at reducing skin bacterial
      load when compared with skin preparation with 2% chlorhexidine or 4%
      chlorhexidine in healthy volunteers. LEVEL OF EVIDENCE: Basic Science -
      Microbiology. CLINICAL RELEVANCE: The findings of this study indicate that the
      use of a bioelectric dressing after knee surgery can match the standard of care
      of preparing the skin with an antiseptic before surgery.

PMID- 30195952
TI  - Comparison of Curved and Straight Anchor Insertion for SLAP Repair: A Cadaveric
      Study.
AB  - PURPOSE: To compare a curved drill guide with a straight guide for suture anchor
      placement into the posterosuperior glenoid from an anterolateral portal with
      respect to glenoid perforation, drill contact with the suprascapular nerve, and
      maximum load. METHODS: Ten bilateral pairs of fresh human cadaveric shoulders
      were randomized to the curved technique on 1 side and the straight technique on
      the contralateral side. An anterolateral trans-rotator cuff portal was used for
      placement of anchors at the posterior (11 o'clock right shoulder) and far
      posterior (10 o'clock right shoulder) positions on the glenoid with a 24-mm drill
      stop, and the drill tip was marked with ink. Specimens were dissected for glenoid
      perforation and drill contact with the suprascapular nerve. The maximum load of
      each anchor was measured using a material testing system. RESULTS: Glenoid
      perforation occurred in 30% in the curved group and 60% in the straight group
      overall (P = .01). Ink markings demonstrated a direct hit on the suprascapular
      nerve in most of the penetrations (13 of 18) but was not significantly different
      between the curved and straight guides (P = .25). Maximum load of the posterior
      anchor was greater in the curved group than that in the straight group (199.5 vs
      146.7 N, respectively; P = .01). CONCLUSIONS: The curved technique has a lower
      rate of glenoid perforation and greater maximum load than the straight technique.
      However, the curved technique can result in glenoid perforation and injury to the
      suprascapular nerve, and we do not recommend it. CLINICAL RELEVANCE: Placing
      suture anchors through an anterolateral portal with a curved guide provides a
      more optimal trajectory with decreased risk of glenoid perforation and superior
      biomechanical strength than that with the straight guide, but it is not safe.

PMID- 30195953
TI  - No Functional Difference Between Three and Six Weeks of Immobilization After
      Arthroscopic Rotator Cuff Repair: A Prospective Randomized Controlled Non
      Inferiority Trial.
AB  - PURPOSE: The aim of this study was to compare clinical and radiologic results
      among patients with 3 versus 6 weeks of immobilization after arthroscopic rotator
      cuff (RC) repair in a prospective randomized controlled non-inferiority trial.
      METHODS: One hundred twenty patients were included after RC surgery for a small-
      to medium-sized tear of supraspinatus and upper infraspinatus tendons. Group A
      was immobilized in a simple sling for 3 weeks, and group B had a brace with a
      small abduction pillow with the arm in neutral position for 6 weeks. All patients
      started active range of motion when they removed the sling/brace. One hundred
      eighteen (98%) patients were assessed at 1-year follow-up. They underwent
      magnetic resonance imaging (MRI) of the shoulder, filled out the Western Ontario
      Rotator Cuff (WORC) index, and were evaluated with a Constant Murley (CM) score.
      RESULTS: Statistical non-inferiority was demonstrated for the 2 groups on the
      basis of the WORC index, the primary endpoint at 1 year. The objective for the
      non-inferiority test was to determine whether the expected mean WORC index for
      group A was at most 13% worse than standard treatment (Group B). The WORC index
      at 1 year was similar in both groups, with mean percent scores of 83% in group A
      and 87% in group B (mean difference = -4; 95% one-sided CI -9, -4). Age-adjusted
      CM scores were also similar, with means of 86 in group A and 90 in group B (mean
      difference = -4; 95% CI -13, 5; P = .37). MRI after 1 year showed 50 (89%)
      patients in each group with healed RC repair. Four patients in group A had
      complications: 1 acute postoperative infection, 2 cases of postoperative
      capsulitis treated with corticosteroid injections, and 1 repeat operation because
      of a loose anchor and subacromial pain. No patients in group B had complications.
      CONCLUSION: RC repair resulted in improved postoperative shoulder function,
      regardless of whether the shoulder was immobilized for 3 or 6 weeks. Three weeks
      of postoperative immobilization with sling use was non-inferior to the commonly
      used regimen involving 6 weeks of immobilization in a brace with regard to the
      WORC index at 12 months' follow-up. MRI indicated similar degrees of healing
      between the groups. Based on these findings, it is safe to immobilize patients in
      a simple sling for 3 to 6 weeks after repair of small to medium RC tears. LEVEL
      OF EVIDENCE: Level I, high-quality randomized controlled trial with statistically
      significant differences.

PMID- 30195954
TI  - Arthroscopic Repair of Acetabular Cartilage Lesions by Chitosan-Based Scaffold:
      Clinical Evaluation at Minimum 2 Years Follow-up.
AB  - PURPOSE: To evaluate the functional outcome of using chitosan-based material in
      our patients after 2 years of follow-up. METHODS: Nonarthritic nondysplastic
      femoroacetabular impingement patients with an acetabular chondral lesion, 18 to
      55 years of age, were included for arthroscopic repair between May 2013 and July
      2015. Full-thickness chondral defects >=2 cm2 were filled with chitosan-based
      implant after microfractures. Follow-up consisted of alpha angle assessment and
      clinical outcome in the form of the Non Arthritic Hip Score (NAHS), International
      Hip Outcome Tool 33 (iHOT33), Hip Outcome Score of Activities of Daily Living
      (HOS-ADL), and Hip Outcome Score of Sports Specific Scale (HOS-SSS). RESULTS:
      Twenty-three patients were included. The mean follow-up was 38.4 +/- 7.0 months
      (range, 24-50 months). The mean defect size was 3.5 +/- 1.0 cm2, principally
      involving zone 2 and to a lesser extent in zones 1 and 3. Using femoroplasty, the
      alpha angle was corrected from a mean 70.5 +/- 6.3 degrees  to 44.3 +/- 4.9
      degrees  (P = .00001). Significant improvement occurred comparing the
      preoperative to the first-year postoperative patient-reported outcomes: P =
      .00001 for the NAHS, P = .00004 for the iHOT33, P = .00005 for the HOS-ADL, and P
      = .0002 for the HOS-SSS. No statistically significant change has been observed in
      the patient-reported outcomes obtained at the endpoint when compared with the
      first-year values (P = .13 for the NAHS, P = .21 for the HOS-ADL, and P = .29 for
      the HOS-SSS), except for the iHOT33, which showed further significant improvement
      (P = .02). Up to 91% of the patients met or exceeded the minimal clinically
      important difference. One patient needed total hip arthroplasty. Perineal
      hypoesthesia occurred in 3 patients, who recovered within 2 to 6 weeks, and 1
      patient needed a prolonged physiotherapy program for postoperative muscular
      stiffness. CONCLUSIONS: The arthroscopic combined treatment of microfractures and
      chitosan-based scaffold has maintained satisfactory clinical outcomes in 91% of
      the patients with s large (>=2 cm2) full-thickness acetabular chondral defect
      associated with femoroacetabular impingement at a mean follow-up of 38.4 months.
      The study could not definitely draw any conclusion regarding the safety of
      chitosan-based material for use in the hip joint. LEVEL OF EVIDENCE: Level IV,
      case series.

PMID- 30195955
TI  - Gravity Fluid Flow More Accurately Reflects Joint Fluid Pressure Compared With
      Commercial Peristaltic Pump Systems in a Cadaveric Model.
AB  - PURPOSE: To evaluate intra-articular fluid pressures and joint compliance
      generated by fluid management systems on cadaveric shoulders and knees under
      simulated arthroscopic conditions, and to compare joint compliance between knee
      and shoulder specimens. METHODS: Intra-articular pressures of 5 cadaver shoulders
      and 5 knees were recorded for 4 arthroscopic pumps (Stryker FloControl, Stryker
      CrossFlow, Arthrex DualWave, DePuy Mitek FMS Duo) and a gravity feed system. Each
      specimen was tested 6 times with a pressure transducer for 2 minutes at 0, 25%,
      and 50% suction. The average pressures were analyzed with 1-way analysis of
      variance and Tukey's honestly significant difference tests (P < .05). RESULTS: At
      all suction levels, all pumps exhibited significantly greater pressure than
      gravity feed (P = .001 to P < .001). At both 25% and 50% suction, FloControl
      displayed significantly greater pressures (Pmax 160.44 mm Hg) than the other
      pumps or gravity feed (Pmax 46.9 mm Hg). CrossFlow had the lowest net percentage
      error (36.8%, 18.4 mm Hg) when compared with the standard pressure of 50 mm Hg,
      followed by gravity feed. All pumps had large initial overshoot (ie, Pinitial
      CrossFlow 99.4 mm Hg) followed by settling time, whereas gravity feed did not
      (Pinitial 55.2 mm Hg). CONCLUSIONS: Gravity feed is an accurate, reliable
      delivery method for arthroscopic fluid with minimal overshoot and lower intra
      articular pressure ranges than commercial pump systems. There was no evidence of
      plastic deformation of the joint capsule, because capsular compliance increased
      linearly in both knee and shoulder specimens throughout testing within the
      established safe range of intra-articular pressures. CLINICAL RELEVANCE:
      Arthroscopic flow management systems produce maximal and overshoot pressures that
      are not seen with gravity flow. Surgeons should understand intra-articular
      pressure and fluid delivery behavior during shoulder and knee arthroscopy to
      adapt to the variability and higher maximal pressures when using pump systems.
      Maintaining appropriate pressure could prevent fluid extravasation and possible
      neuromuscular dysfunction.

PMID- 30195956
TI  - Higher Critical Shoulder Angle and Acromion Index Are Associated With Increased
      Retear Risk After Isolated Supraspinatus Tendon Repair at Short-Term Follow Up.
AB  - PURPOSE: To evaluate the effect of critical shoulder angle (CSA), acromion index
      (AI), and glenoid inclination (GI) on the postoperative healing rate after
      arthroscopic supraspinatus tendon repair. METHODS: Patients after arthroscopic
      repair of a symptomatic, unilateral, single-tendon, full-thickness supraspinatus
      tear in whom nonoperative management had failed were retrospectively reviewed.
      Magnetic resonance imaging (MRI) studies were obtained 6 months postoperatively
      and were evaluated by 2 independent observers. Repair integrity was classified as
      either intact or torn. Preoperative true anteroposterior radiographs were used to
      measure CSA, AI, and GI. RESULTS: Fifty-seven patients were evaluated 6 months
      postoperatively. The mean patient age at surgery was 54.7 +/- 7.7 years. On MRI
      studies, 41 patients (71.9%) had an intact repair and 16 patients (28.1%) had a
      full-thickness retear. There were no significant differences between the intact
      and retear group in regard to patient age (P = .648), initial tear size (P =
      .205), or fatty degeneration (P = .508). The mean CSA for the retear group (37
      degrees  +/- 4 degrees ) was significantly higher than that in the intact group
      (35 degrees  +/- 3 degrees ; P = .014). If the CSA was >38 degrees , the odds
      ratio of having a retear was 3.78 (95% confidence interval 1.05 to 13.58; P =
      .042). Average AI for the retear group (0.73 +/- 0.09) was significantly higher
      than that in the intact group (0.69 +/- 0.06; P = .049). The mean GI was 17
      degrees  +/- 6 degrees  for the intact group and 16 degrees  +/- 6 degrees  for
      the retear group (P = .739). CONCLUSIONS: At short-term follow-up, higher CSA and
      AI significantly increased the retear risk after arthroscopic supraspinatus
      tendon repair. CSA >38 degrees  increased the retear risk almost 4-fold. Overall
      GI was elevated but did not correlate with failure rate. LEVEL OF EVIDENCE: III,
      case control study.

PMID- 30195957
TI  - Time From Injury to Surgery Affects Graft Maturation Following Posterior Cruciate
      Ligament Reconstruction With Remnant Preservation: A Magnetic Resonance Imaging
      Based Study.
AB  - PURPOSE: To evaluate the clinical outcomes and graft maturation following
      posterior cruciate ligament reconstruction (PCLR) with preserved remnant and
      further analyze the correlated factors affecting graft maturation. METHODS:
      Consecutive patients who underwent unilateral single-bundle PCLR with remnant
      preservation from January 2011 to October 2014 by the same senior doctor using
      tibialis anterior allografts and same surgical technique were included. At a
      follow-up of more than 2 years, range of motion (ROM) and posterior laxity
      assessed by posterior drawer test and the KT-1000 arthrometer were examined.
      Tegner, Lysholm, and International Knee Documentation Committee scores were
      evaluated. The graft maturation was assessed by a 3.0-T magnetic resonance
      imaging. Overall correlation analyses and multivariate regression analysis were
      performed to identify correlated factors of graft maturation, and then subgroups
      were divided and analyzed according to significant risk factor. RESULTS: Forty
      three (84.3%) of 51 enrolled patients were successfully followed up (38.4 months,
      24-54 months). All clinical scores improved significantly, and there were no
      complications. The results of KT-1000 difference revealed significant decline of
      posterior laxity (9.4 +/- 1.5 vs 2.2 +/- 1.5 mm; P < .001). The MRI evaluation
      confirmed no ligament retears. Both correlation and regression analyses showed
      time from injury to surgery had a positive, statistically significant weak
      correlation with the signal intensity score (R = 0.38, P = .012; coefficient =
      0.10; P = .036). Subgroup (group 1: time from injury to surgery <3 months; group
      2: 3-6 months; group 3: 6-12 months; group 4: >=12 months) analysis showed there
      were no significant differences of clinical outcomes between subgroups, while MRI
      signal intensity was significantly lower in the group with shorter time from
      injury to surgery (P = .02). CONCLUSIONS: The remnant-preserved PCLR resulted in
      satisfactory clinical outcomes and graft maturation at a mean follow-up of 38.4
      months. The time from injury to surgery showed a weak positive correlation with
      postoperative graft signal intensity on MRI. LEVEL OF EVIDENCE: Level III,
      retrospective comparative study.

PMID- 30195958
TI  - Risk of Retear Following Anterior Cruciate Ligament Reconstruction Using a Hybrid
      Graft of Autograft Augmented With Allograft Tissue: A Systematic Review and Meta
      analysis.
AB  - PURPOSE: To compare the risk of anterior cruciate ligament reconstruction failure
      in patients who undergo anterior cruciate ligament reconstruction with either
      autograft tissue or hybrid grafts. METHODS: A systematic search was performed on
      February 28, 2018, on PubMed, Scopus, Arthroscopy, and Cochrane Library. Included
      studies were clinical outcome studies of primary anterior cruciate ligament
      reconstructions that compared failure risk for hybrid grafts versus autografts.
      Baseline and outcomes data were extracted, and reporting quality was assessed via
      modified Coleman criteria. A random effects meta-analysis was conducted for both
      randomized and nonrandomized studies. RESULTS: Nine studies were identified with
      a mean of 40.1 months of follow-up. The mean Coleman methodology score was 66.5
      (standard deviation, 12.8). One randomized study (Level II evidence) was
      identified with no difference in failure rates (0% for both groups, 8-mm minimum
      graft diameter for all patients). Eight nonrandomized studies (all Level III
      evidence) were identified with no difference in failure risk for hybrid grafts
      versus autograft (pooled odds ratio, 1.29; 95% confidence interval, 0.57-2.92; P
      = .55; I2 = 34%). Mean graft diameters were significantly larger in hybrid groups
      (range, 8.5-9.9 mm) than in autograft groups (range, 6.4-8.8 mm) in nonrandomized
      studies (mean difference, 0.5-2.5 mm; P <= .003). There was no evidence of small
      study bias or bias owing to reporting quality, and adjustment for length of
      follow-up, mean patient age, percentage of male patients, year of publication, or
      reporting quality did not improve statistical heterogeneity. CONCLUSIONS: Based
      on the current literature, although it may be theoretically detrimental to add
      allograft to a small-diameter autograft, it cannot be definitively shown based on
      the findings of this review with meta-analysis. Currently, it remains unclear
      that there is an advantage or disadvantage to hybridization of small autograft
      with allograft, although randomized studies of patients with small (<8-mm)
      autograft diameters are lacking. LEVEL OF EVIDENCE: Level III, systematic review
      of Level II and III studies.

PMID- 30195959
TI  - The Clinical Outcomes and Their Associated Factors in Staged Bilateral
      Arthroscopic Rotator Cuff Repair.
AB  - PURPOSE: To compare perioperative characteristics and postoperative outcomes of
      both shoulders in patients who underwent arthroscopic bilateral rotator cuff
      repair sequentially and to assess the associated factors that would affect the
      anatomic healing in staged bilateral rotator cuff repair. METHODS: The study
      enrolled 64 patients who underwent bilateral rotator cuff repair with follow-up
      imaging at least 12 months postoperatively. We allocated the shoulders operated
      on first to the surgery I group and those operated on second to the surgery II
      group. Visual analog scale (VAS) pain and satisfaction scores, range of motion,
      the American Shoulder and Elbow Surgeons score, the Simple Shoulder Test score,
      and healing failure were evaluated. RESULTS: Range of motion improved with no
      significant between-group differences (all P > .05). In the surgery II group, VAS
      pain and VAS satisfaction scores were significantly worse at 6 months
      postoperatively (P = .048 and P = .041, respectively) but were comparable at
      final follow-up (P = .598 and P = .065, respectively). American Shoulder and
      Elbow Surgeons and Simple Shoulder Test scores at 6 months were worse in the
      surgery II group (P = .038 and P = .048, respectively) but similar at final
      follow-up (P = .786 and P = .087, respectively). Tear size was similar between
      the 2 surgical procedures (kappa = 0.537, P < .001). Of the 11 patients with
      nonhealing in the surgery I group, 7 (63.6%) had subsequent failure in the other
      shoulder, and if one shoulder had healing failure, the other shoulder had a high
      possibility of healing failure as well (kappa = 0.373, P = .004). CONCLUSIONS:
      Bilateral arthroscopic rotator cuff repair showed good outcomes at final follow
      up on both sides. Tear size was closely related in both shoulders, and healing
      failure after the first rotator cuff repair was an associated factor with healing
      failure after the second operation. LEVEL OF EVIDENCE: Level IV, case series.

PMID- 30195960
TI  - Recurrence Rate of Instability After Remplissage for Treatment of Traumatic
      Anterior Shoulder Instability: A Systematic Review in Treatment of Subcritical
      Glenoid Bone Loss.
AB  - PURPOSE: To report outcomes after arthroscopic remplissage in patients with
      anterior shoulder instability and subcritical glenoid bone loss, specifically
      regarding recurrence of instability, return to sport, and changes in range of
      motion. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta
      Analyses guidelines were used to perform a search using the PubMed, Embase,
      Cochrane Library, and Scopus databases. Forest plots were used to evaluate the
      overall values for recurrent instability, change in external rotation, and return
      to sport after arthroscopic Bankart repair with or without remplissage. The
      Methodological Index for Non-randomized Studies and Risk of Bias in Nonrandomized
      Studies-Interventions checklist were used to evaluate bias. RESULTS: Twenty-two
      articles met the inclusion and exclusion criteria. The Methodological Index for
      Non-randomized Studies and Risk of Bias in Nonrandomized Studies-Interventions
      checklists deemed studies as acceptable quality with low bias. Among 694 patients
      (522 male and 106 female patients) undergoing remplissage, the mean age was 28.3
      +/- 5.3 years and the mean duration of follow-up was 32.5 +/- 13.9 months. The
      recurrence rate of instability ranged from 0% to 20%. The change in external
      rotation in 90 degrees  of abduction ranged from -11.3 degrees  to -1.0 degrees ,
      and the change in external rotation with the arm fully adducted ranged from -8.0
      degrees  to +4.5 degrees . The overall rate of return to sport ranged from 56.9%
      to 100% after remplissage. The rate of return to sport at the preinjury level
      ranged from 41.7% to 100%. In addition, arthroscopic remplissage in addition to
      Bankart repair had a reduced odds of recurrent instability developing, ranging
      from 0.07 to 0.88, when compared with isolated Bankart repair. CONCLUSIONS:
      Arthroscopic remplissage combined with Bankart repair is an effective procedure
      in the treatment of patients with engaging Hill-Sachs lesions and minimal glenoid
      bone loss. Patients can expect favorable rates of recurrent instability with a
      negligible loss of external rotation when compared with isolated Bankart repair.
      Treatment algorithms may be updated to include this procedure for engaging Hill
      Sachs lesions, measuring between 20% and 40% in volume, with subcritical (<20%)
      glenoid bone loss. LEVEL OF EVIDENCE: Level IV, systematic review of Level III
      and IV studies.

PMID- 30195961
TI  - Epidemiology and Detrimental Impact of Opioid Use in Patients Undergoing
      Arthroscopic Treatment of Femoroacetabular Impingement Syndrome.
AB  - PURPOSE: To determine the prevalence of preoperative opioid use in patients with
      femoroacetabular impingement (FAI) syndrome and to define how opioid use
      influences preoperative hip pain and function at a single center. METHODS:
      Between February 2015 and September 2016, patients undergoing hip arthroscopy at
      a single Midwest institution for FAI syndrome were retrospectively reviewed.
      Patients undergoing arthroscopy for non-FAI conditions and those with
      undocumented preoperative opioid use were excluded. Baseline validated measures
      (Hip Disability and Osteoarthritis Outcome Score [HOOS] pain and physical
      function; University of California, Los Angeles, activity scores; Veterans RAND
      12 Item Health Survey) of health were collected at the time of surgery. Articular
      cartilage status was documented at the time of surgery. Opioid use was extracted
      from the electronic medical record retrospectively, and patients were designated
      current users, past users, or nonusers. Analysis of variance and 2-tailed
      Student's t-tests were used to detect differences between groups according to
      preoperative opioid use, and significance was set to P < .05. RESULTS: During the
      study period 321 patients underwent arthroscopic hip surgery for FAI and met the
      inclusion criteria (75 were excluded). Preoperatively, 55 patients (17%) were
      current opioid users, 89 (28%) were past users (not within 3 months of surgery),
      and 177 (55%) were opioid naive. Current opioid use was associated with
      significantly worse measures of joint and general health including HOOS-Pain
      (15.3 point difference, P < .001), HOOS-Physical Function (13.6 point difference,
      P < .001), University of California, Los Angeles, activity score (1.7 point
      difference, P < .001), and Veterans RAND 12 Item Health Survey mental component
      score (5.5 point difference, P < .001). Outerbridge cartilage grading and
      presence or length of labral tears were not worse in opioid users (P = .2-.61).
      CONCLUSIONS: Preoperative opioid use is common prior to arthroscopy for FAI and
      has detrimental impacts on hip pain and function. The present data also suggest
      cessation of opioid medication for 3 months prior to surgery may have meaningful
      impacts on baseline measures of hip and general health. LEVEL OF EVIDENCE: Level
      III, prognostic.

PMID- 30195962
TI  - Low additional thickness under the toes could change upright balance of healthy
      subjects.
AB  - The purpose of the study was to evaluate the effect of an additional thickness
      placed under the toes (TUT) on the CoP measures and to determine the optimum
      thickness required to maximize the postural control performance. Four conditions
      were compared: TUT 0 (control), 0.8, 3, and 6mm and four variables were computed
      from the CoP displacements. These results suggest that the lowest TUT could
      contribute to changing balance control, and may have clinical interest. This
      brings perspectives in the management of patients with risk of falling or with
      chronic pain syndromes, complementing validated therapeutic strategies.

PMID- 30195963
TI  - A Rare Case of Recurrent Coronary Cameral Fistula: A Unique Surgical Challenge.

PMID- 30195964
TI  - History of Cardiac Anesthesia in New Zealand.
AB  - New Zealand has a long and proud history of innovation in cardiac surgery and
      anesthesia. There have been a number of prominent men and women who have
      contributed to the development of cardiac anesthesia in New Zealand. There are
      numerous ongoing challenges in providing cardiac anesthetic services to the
      population of New Zealand.

PMID- 30195965
TI  - Minocycline Before Aortic Occlusion Reduces Hindlimb Motor Impairment, Attenuates
      Spinal Cord Damage and Spinal Astrocytosis, and Preserve Neuronal
      Cytoarchitecture in the Rat.
AB  - OBJECTIVES: Spinal cord ischemia secondary to trauma or a vascular occlusive
      event is a threatening phenomenon. The neuroprotective properties of minocycline
      have been shown in several models of central nervous system diseases and after
      spinal cord ischemia; however, the benefit of using the drug requires additional
      confirmation in different animal models. Astrocytes are essential as regulators
      of neuronal functions and for providing nutrients. The authors hypothesized that
      astrocytes in the spinal cord may be an important target for minocycline action
      after ischemia and thus in the prevention of secondary spreading damage. DESIGN:
      A prospective, randomized animal study. SETTING: University research laboratory,
      single institution. PARTICIPANTS: Adult male Sprague Dawley rats, weighing
      between 400 and 450 g. INTERVENTIONS: A model of spinal cord ischemia in the rat
      was used for this study to determine whether a single, high-dose (10 mg/kg) of
      minocycline protects against damage to the neuronal cytoskeleton, both in the
      white and gray matter, and whether it reduces glial fibrillary acidic protein
      levels, which is an index for prevention of astrocyte activation during ischemia.
      Thirty minutes before thoracic aorta occlusion, minocycline was administered for
      18 minutes using a 2 F Fogarty catheter. MEASUREMENTS AND MAIN RESULTS:
      Minocycline given prophylactically significantly mitigated severe hindlimb motor
      impairment and reduced glial fibrillary acidic protein plus astrocytosis in both
      the white and gray matter of the spinal cord, caudal to the occlusion. Neuronal
      histologic cytoarchitecture, which was severely and significantly compromised in
      control animals, was preserved in the minocycline-treated animals. CONCLUSIONS:
      This study's data imply that minocycline may attenuate reactive astrocytosis in
      response to injury with better neurologic outcome in a model of spinal cord
      ischemia in rats. The data suggest that future use of minocycline, clinically,
      might be advantageous in surgeries with a potential risk for paraplegia due to
      spinal cord ischemia.

PMID- 30195966
TI  - Semaglutide: Review and Place in Therapy for Adults With Type 2 Diabetes.
AB  - Guidelines increasingly highlight the importance of multifactorial management in
      type 2 diabetes, in contrast to the more traditional focus on glycemic control.
      Semaglutide, a recently approved glucagon-like peptide-1 receptor agonist, is
      indicated in Canada for adults with type 2 diabetes to improve glycemic control
      as monotherapy with diet and exercise when metformin is inappropriate or as an
      add-on to either metformin alone or metformin plus a sulfonylurea or basal
      insulin. The Semaglutide Unabated Sustainability in Treatment of Type 2 Diabetes
      (SUSTAIN) clinical trial program for semaglutide comprises 6 pivotal global phase
      3a trials (SUSTAIN 1 through 6) and 2 Japanese phase 3a trials. Phase 3b trials
      include SUSTAIN 7, and SUSTAIN 8 and 9 (both ongoing). Results from the completed
      trials support the superiority of semaglutide for reduction of glycated
      hemoglobin levels and weight loss vs. placebo as well as active comparators,
      including sitagliptin, exenatide extended-release, dulaglutide and insulin
      glargine. SUSTAIN 6 trial data confirmed cardiovascular safety and demonstrated
      significant reductions in major cardiovascular events with semaglutide vs.
      placebo, an outcome that confirmed the noninferiority of semaglutide. The robust
      and sustained effects of semaglutide on glycated hemoglobin levels and weight
      loss vs. comparators, as well as its safety and possible cardiovascular benefit,
      address an unmet need in the treatment of type 2 diabetes. This article overviews
      data from across the semaglutide clinical trial program, including efficacy and
      safety results and findings from post hoc analyses. The potential place of
      semaglutide in clinical practice is discussed.

PMID- 30195967
TI  - Body dissatisfaction and its relationship with overweight, sedentary behavior and
      physical activity in survivors of breast cancer.
AB  - OBJECTIVES: This study aimed to verify the prevalence of body satisfaction in
      breast cancer survivors and the association of this variable with overweight,
      sedentary behavior and physical activity in this population. STUDY DESIGN: This
      is a cross-sectional study realized in Presidente Prudente-Brazil. Breast cancer
      survivors participated in this study. Questionnaires were used to obtain data on
      socioeconomic status, body dissatisfaction, sedentary behavior and level of
      physical activity. The association between body dissatisfaction and the
      independent variables was verified through binary logistic regression in the
      unadjusted model and model adjusted by socioeconomic level. RESULTS: A total of
      102 breast cancer survivors participated in this study with a mean age of 58.2
      (+/-10.3) years. The prevalence of body dissatisfaction was 75.7%. Body
      dissatisfaction was higher in women with higher BMI (pvalue = 0.003) and in woman
      with high sedentary behavior (p-value = 0.049). Women with overweight had 7.87
      times more chance of presenting body dissatisfaction. Women who reported hormone
      therapy were approximately 3 times more likely to be dissatisfacted with their
      body. CONCLUSION: Body dissatisfaction was associated with lower age, high
      sedentary behavior and overweight in breast cancer survivors in the unadjusted
      analysis. When adjusted for socioeconomic status, only the variables of
      overweight and hormone therapy were associated with body dissatisfaction.

PMID- 30195968
TI  - Molecular identification of steroidogenesis-related genes in scallops and their
      potential roles in gametogenesis.
AB  - Sex steroids are crucial for controlling gametogenesis and germ cell maturation
      in vertebrates. It has been proposed that Yesso scallop (Mizuhopecten yessoensis)
      has the same sex steroids as those animals, but the scallop biosynthetic pathway
      is unclear. In this study, we characterized several steroidogenesis-related genes
      in M. yessoensis and proposed a putative biosynthetic pathway for sex steroids
      that is similar to that of vertebrates. Specifically, we identified several
      steroidogenesis-related gene sequences that encode steroid metabolizing enzymes:
      StAR-related lipid transfer (START) protein, 17alpha-hydroxylase, 17,20-lyase
      (cyp17a), 17beta-hydroxysteroid dehydrogenase (hsd17b), and 3beta-hydroxysteroid
      dehydrogenase (hsd3b). We sampled adult scallops throughout their reproductive
      phase to compare their degree of maturation with their intensity of mRNA
      expression. Semi-quantitative RT-PCR analysis revealed a ubiquitous expression of
      transcripts for steroid metabolizing enzymes (i.e., star, cyp17a, hsd17b, and
      hsd3b) in peripheral and gonadal tissues. Real-time PCR analysis revealed a high
      level of expression of star3 and cyp17a genes in gonadal tissues at the early
      stage of cell differentiation in scallops. Interestingly, mRNA expression of
      hsd3b and hsd17b genes showed a synchronous pattern related to degree of gonad
      maturity. These results indicate that both hsd3b and hsd17b genes are likely
      involved in steroidogenesis in scallops. We therefore believe that these steroid
      metabolizing enzymes allow scallops to endogenously produce sex steroids to
      regulate reproductive events.

PMID- 30195969
TI  - Management of dental extractions in patients on warfarin and antiplatelet
      therapy.
AB  - BACKGROUND/PURPOSE: Planning dental extractions for Taiwanese patients on
      antithrombotic therapy remains controversial. This study aimed to examine
      management of dental extraction in patients on warfarin and antiplatelet therapy.
      METHODS: Subjects comprised 1331 patients, with (1) 60 on warfarin with
      intentional normalized ratio (INR) below 4.0 (warfarin continued: 28 patients/33
      occasions; warfarin stopped and switched to heparin under hospitalization: 32
      patients/37 occasions); (2) 183 on antiplatelet therapy (aspirin: 125
      patients/185 occasions; clopidogrel: 42 patients/65 occasions; dual therapy: 16
      patients/24 occasions); and (3) a control group of 1088 patients/1472 occasions
      without any antithrombotic therapy. The patient's clinico-demographic parameters,
      warfarin effectiveness (dose and INR levels) and antiplatelet therapy, number and
      type of dental extraction and incidence of postoperative bleeding were
      investigated. RESULTS: Incidence of postoperative bleeding in the warfarinized
      group (warfarin continued: 9.1%; warfarin stopped: 8.1%) was higher than in the
      antiplatelet group (aspirin: 1.1%; clopidogrel: 3.1%; dual antiplatelet: 4.2%),
      and the control group (0.7%), but these differences were not significant and
      unrelated to INR or number and type of dental extraction. Postoperative
      hemorrhage was managed successfully by repacking with Gelfoam impregnated with
      tranexamic acid powder in most patients. CONCLUSION: The study indicated that
      there is no need to interrupt warfarin (INR<4.0) and antiplatelet therapy before
      dental extractions in Taiwanese patients. A sufficient hemostasis could be
      obtained using local measures. This approach can save these individuals from
      becoming exposed to the risk of thromboembolism and the inconvenience of bridging
      anticoagulation with heparin.

PMID- 30195970
TI  - A single-institution study of predisposing factors of patients with BAVMs to flow
      related aneurysm.
AB  - BACKGROUND AND PURPOSE: The goal of this study was to assess the potential risk
      factors leading to flow-related aneurysm (FA) formation in patients with brain
      arteriovenous malformations (BAVMs) in Taiwanese. METHODS: We recruited 890
      patients with BAVMs: 72 had FA(s) and 818 did not. Several factors were assessed
      including patient's age, gender, BAVM volume and location, and Spetzler-Martin
      grade. RESULTS: The 890 patients with BAVM had a mean age of 30 years (range: 2
      84), mean BAVM volume of 10.6 mL (range: 0.13-91.4). BAVMs were ruptured in 42%
      of patients. Compared to BAVM patients without FAs, the 72 patients with FAs had
      older age (mean 41 yrs vs 31 yrs, p < 0.001); larger average BAVM volume (39.6 mL
      vs 16.1 mL, p < 0.001). No statistical significance in Spetzler-Martin grades
      (chi2 value = 8.687 and p = 0.122) was found in terms of formation of FA. FA
      demonstrated similar gender distribution and BAVM location distribution (the chi2
      value was 0.242 and 0.812, respectively). CONCLUSIONS: Patients with older age
      and large BAVM volume are more prone to FA. Gender, BAVM location, and BAVM grade
      are not statistically significant predisposing factors for FA.

PMID- 30195971
TI  - Towards closed-loop deep brain stimulation for freezing of gait in Parkinson's
      disease.

PMID- 30195972
TI  - Fast changes of NMDA and AMPA receptor activity under acute hyperammonemia in
      vitro.
AB  - It was established in experiments on cell cultures of neurons and astrocytes that
      ammonium ions at concentrations of 4-8 mM cause hyperexcitation of the neuronal
      network, as a result of which there is a disturbance of calcium homeostasis,
      which can lead to the death of neurons. In the present study, we investigated the
      effect of toxic doses of ammonium (8 mM NH4Cl) on the activity of NMDA and AMPA
      receptors and the role of these receptors in spontaneous synchronous activity
      (SSA). In a control experiment in the absence of NH4Cl, SSA is not suppressed by
      NMDA receptor inhibitors, but is suppressed by AMPA receptor antagonists. In the
      presence of toxic doses of NH4Cl, SSA is completely inhibited by NMDA receptor
      inhibitors in 63% of neurons and by AMPA receptor inhibitors in 33% of neurons.
      After short-term applications of toxic doses of ammonium, the amplitude of the
      Ca2+ response to 10 MUM NMDA increases, and decreases in response to 500 nM FW
      (agonist of AMPA receptors). NMDA receptor blocker MK-801 (20 MUM), competitive
      antagonist D-AP5 (10 MUM) and competitive AMPA receptor antagonist NBQX (2 MUM)
      abolished the activating ammonium mediated effect on the NMDA receptors while
      only MK-801, but not NBQX, abolished the inhibiting ammonium mediated effect on
      AMPA receptors. These data indicate that under acute hyperammonemia, the activity
      of NMDA receptors increases, while the activity of AMPA receptors decreases. This
      phenomenon could explain such a wide range of toxic effects of ammonium ions
      mediated by NMDA receptors.

PMID- 30195973
TI  - Alterations of static functional connectivity and dynamic functional connectivity
      in motor execution regions after stroke.
AB  - The aims of this study were to examine both static functional connectivity (FC)
      and dynamic FC alterations in motor execution regions after stroke and to
      investigate whether the altered static or dynamic FC was associated with the
      clinical behaviors in stroke patients. Seventy-six stroke patients and 55 healthy
      controls (HC) were recruited. Static FC and dynamic FC maps were computed based
      on the seeds of six core regions in motor execution network. Correlation analyses
      were performed between static or dynamic FC and clinical behavioral scores in
      stroke patients. Compared with the HC, the stroke patients had significantly
      higher static FC between the seeds and the precentral or postcentral gyrus,
      frontal gyrus, inferior parietal lobule, thalamus and insula, and lower static FC
      between the seeds and the cerebellum and middle temporal gyrus. There were
      significant differences in dynamic FC between the seeds and precuneus, calcarine
      gyrus, insula, inferior parietal lobule, precentral gyrus, and middle temporal,
      frontal or occipital gyrus between the stroke patients and HC. Furthermore, a
      significant negative correlation was found between the Fugl-Meyer assessment
      scores and dynamic FC of the ipsilesional primary motor cortex and contralesional
      precentral gyrus in patients. The current study shows that the patterns of both
      static FC and dynamic FC changed after stroke, and correlation between motor
      function and temporal variability in the FC of the precentral gyrus was
      significant in stroke patients. Our findings indicate that dynamic FC might be a
      potential indicator for evaluating motor function after stroke.

PMID- 30195974
TI  - Feedback-related negativity reflects omission of monetary gains: Evidence from
      ERP gambling study.
AB  - Feedback processing is an important aspect of learning. In the human brain,
      feedback processing is often examined by measuring an event-related potential,
      the feedback-related negativity component. Typically, the feedback-related
      negativity component is investigated by directly comparing gain with loss
      feedback randomized across trials; however, this method does not control for
      confounds associated with unexpected feedback. For this study we used a blocked
      design gambling task to investigate the sensitivity of feedback-related
      negativity to positive and negative feedback separately for gains and losses.
      While there appeared to be no significant feedback-related negativity in the loss
      domain, results revealed an enlarged feedback-related negativity during the
      omission of gains compared to the reception of gains. These findings further
      support the reward positivity hypothesis which declares that the feedback-related
      negativity is associated with the processing of outcomes in the context of gains
      as opposed to losses, irrespective of unexpectedness.

PMID- 30195975
TI  - Chasing the zone: Reduced beta power predicts baseball batting performance.
AB  - Mental state prior to sports skill execution is related to subsequent
      performance. For example, relationships between pre-performance
      electroencephalogram (EEG) power and subsequent movement outcomes in golf
      putting, pistol shooting, and basketball free throw shooting have been previously
      reported. With that said, the existing body of research examining the pre
      performance EEG - performance relationship has been focused on the execution of
      internally as opposed to externally-paced motor skills. Given that the execution
      of internally and externally-paced movements are dependent on different neural
      pathways, in the present study we examined whether or not pre-performance EEG
      power predicted ensuing performance of an externally-paced motor skill - baseball
      batting. Sixty-seven baseball players had EEG data recorded for 120 s prior to
      batting practice. Performance was assessed by three expert coaches and the
      accuracy of coach performance ratings was verified via Generalizability Theory.
      An analysis of our data revealed an inverse relationship between frontal EEG
      power in the beta range and subsequent batting performance - reduced beta power
      was associated with better batting performance whereas increased beta power was
      associated with worse batting performance. Our results are in line with prior
      research that has demonstrated a relationship between increased EEG power in the
      beta range and the subsequent commitment of motor errors in addition to the
      aforementioned work examining pre-performance EEG and the execution of internally
      paced motor skills.

PMID- 30195976
TI  - Cadmium selenide quantum dot-zinc oxide composite: Synthesis, characterization,
      dye removal ability with UV irradiation, and antibacterial activity as a safe and
      high-performance photocatalyst.
AB  - In this paper, cadmium selenide quantum dot (CdSe QD)-zinc oxide (ZnO)
      nanocomposite (CdSe QD-ZnO) was synthesized and characterized and its
      photocatalytic dye degradation ability was investigated. The XRD, FTIR, UV-Vis,
      AFM and SEM were used to characterize the synthesized nanomaterials. The
      correlation coefficient of pseudo-first-order kinetic reaction is 0.98. The rate
      constants from 20 to 30 mg/L of pollutant concentrations was reduced by the order
      of 0.9. The temporal change in dye concentration reduces as the photocatalyst
      dosage increase up to optimum value of 0.04 g/L, then beyond that value the
      increase in the dosage becomes detrimental. Antibacterial activity of the
      synthesized nanocomposite as a safe photocatalyst was studied in details.
      Antibacterial activity of as prepared samples was also examined against
      Escherichia coli (E. coli). For in vitro study, Human umbilical vein endothelial
      cells (HUVEC) was utilized for the modeling of toxicity of each as prepared
      samples as representative of human normal cell line. In vivo study was conducted
      using leeches (Hirudo orientalis). In the presence of ethanol as hydroxyl radical
      (OH) scavenger, the removal efficiency significantly depresses compared to the di
      methyl sulfoxide as electron scavengers suggesting OH possesses a major role in
      photocatalytic dye (Basic Red 18: BR18) decolorization. By coupling with CdSe QD,
      the zone of inhibition was greatly increased suggesting the size dependent
      inactivation of E. coli. The results presented that the composite had no
      significant effect on the proliferation of HUVEC normal cells. In addition, the
      treatment of cells with ZnO and the composite does not impact on the cell
      morphology.

PMID- 30195977
TI  - Photoactivated [Mn(CO)3Br(MU-bpcpd)]2 induces apoptosis in cancer cells via
      intrinsic pathway.
AB  - Carbon monoxide releasing molecules (CORMs) are organometallic/organic compounds
      that release carbon monoxide (CO) spontaneously or upon activation. PhotoCORMs
      are capable of releasing CO on light based activation. This group of molecules is
      used in photodynamic therapy due to their ability to release CO in a controlled
      manner. In the present investigation, the release of CO from [Mn(CO)3Br(MU
      bpcpd)]2 (MnCORM) upon irradiation at lambdamax 365 nm was assessed
      spectrophotometrically using myoglobin assay and confirmed by liquid FT-IR
      spectroscopic analysis. Further, the cytotoxic potential of MnCORM on normal
      cells (HEK 293) and cancer cell lines such as lung (A549), cervical (HeLa),
      breast (MDA MB-231) and colon (HCT-15) was evaluated. The IC50 values of MnCORM
      were found to be 21.37 +/- 1.72, 24.12 +/- 1.03, 21.89 +/- 0.59 and 13.69 +/-
      0.91 MUM on cervical (HeLa), lung (A549), colon (HCT-15) and breast (MDA MB-231)
      cancer cells respectively. An inquest into the nature of cell death was confirmed
      based on the nuclear and cytological examinations, flow cytometric analyses and
      protein expression studies. The AO/EB dual staining and cytological evaluation of
      the treated cells revealed that the cell death might be due to apoptosis. The
      flow cytometric analysis of propidium iodide (PI) stained cells showed a
      significant amount of sub-G1 hypodiploid cells due to MnCORM treatment. The
      MnCORM-induced apoptosis was mediated through the generation of reactive oxygen
      species (ROS), specifically superoxide radicals leading to loss of mitochondrial
      membrane potential. The intrinsic pathway of apoptosis was elucidated based on
      the expression studies of pro-apoptotic and apoptotic proteins such as bcl-2,
      bax, cyt c, cleaved caspase-3, cleaved caspase-9 and cleaved PARP. Due to its
      innate potential to release CO upon photoactivation and its ability to induce
      apoptosis via intrinsic pathway, the MnCORM molecule could be exploited for
      controlled release and photodynamic cancer therapy.

PMID- 30195978
TI  - The roles of IL-6, IL-8 and IL-10 gene polymorphisms in gastric cancer: A meta
      analysis.
AB  - BACKGROUND: Recently, the roles of interleukin-6 (IL-6), IL-8 and IL-10 gene
      polymorphisms in gastric cancer have been extensively studied, with conflicting
      results. Therefore, we conducted the present study to better assess the potential
      correlations between these interleukin gene polymorphisms and gastric cancer.
      METHODS: Eligible articles were searched in PubMed, Medline, Embase, Web of
      Science and CNKI. Odds ratios (ORs) and 95% confidence intervals (CIs) were used
      to detect any potential associations between interleukin gene polymorphisms and
      the risk of gastric cancer. RESULTS: A total of 73 case-control studies were
      finally included. Significant associations with the risk of gastric cancer were
      only detected for the IL-8 rs4073 polymorphism in overall analyses. Further
      subgroup analyses according to ethnicity of participants revealed that the IL-6
      rs1800796, IL-8 rs4073, IL-10 rs1800871, IL-10 rs1800872 and IL-10 rs1800896
      polymorphisms were all significantly associated with the risk of gastric cancer
      in Asians. No positive results were found for any investigated interleukin gene
      polymorphisms in Caucasians. CONCLUSIONS: Our findings suggest that IL-6
      rs1800796, IL-8 rs4073, IL-10 rs1800871, IL-10 rs1800872 and IL-10 rs1800896
      polymorphisms may serve as genetic biomarkers of gastric cancer in Asians.

PMID- 30195979
TI  - Natural killer T cell ligand alpha-galactosylceramide protects against gut
      ischemia reperfusion-induced organ injury in mice.
AB  - BACKGROUND & AIMS: Gut ischemia reperfusion (I/R) injury is a life-threatening
      condition. The immune response plays an important role in I/R-induced organ
      injury. Alpha-galactosylceramide (alpha-GalCer) is a potent natural killer T
      (NKT) cell stimulator. Activation of NKT cells by alpha-GalCer has been shown to
      reduce I/R-induced injury in the liver and heart. However, whether alpha-GalCer
      has any protective effects on gut I/R-induced organ injury remained unknown. The
      aim of this study was to test the hypothesis that alpha-GalCer attenuates gut I/R
      induced local and remote organ injury through modulating immune responses.
      METHODS: Gut ischemia was induced by placing a microvascular clip across the
      superior mesenteric artery for 30 min in male adult mice. After removing the
      clip, alpha-GalCer (2 ug/mouse) or normal saline containing 0.5% Tween 20
      (Vehicle) was administered intraperitoneally. Blood, gut, lung and mesenteric
      lymph node (MLN) samples were collected 4 h after reperfusion to detect bacterial
      translocation, tight junction protein, tissue damage, edema, apoptosis, IL-4, IL
      10, IFN-gamma and TNF-alpha levels. RESULTS: alpha-GalCer significantly reduced
      bacterial translocation to the MLN, restored tight junction protein and
      attenuated gut and lung injury after gut I/R. alpha-GalCer markedly stimulated
      the production of IL-4, IL-10 and IFN-gamma, but had no obvious effects on TNF
      alpha production in gut I/R mice. Pretreatment with anti-CD1d, IL-4 or IL-10, but
      not IFN-gamma blocking antibodies abolished the protective effects of alpha
      GalCer in gut I/R. CONCLUSIONS: alpha-GalCer treatment improved gut barrier
      function and attenuated gut and lung injury after gut I/R. The beneficial effects
      of alpha-GalCer in gut I/R were NKT cell dependent and mediated through
      upregulation of IL-4 and IL-10. Thus, activation of NKT cells by alpha-GalCer may
      serve as a novel option in the treatment of gut I/R injury.

PMID- 30195980
TI  - [Chemotherapy and chemoradiotherapy indications in the treatment of locally
      advanced gastric carcinoma].
AB  - Currently, there is no international consensus on the best treatment regimen for
      patients with advanced resectable gastric carcinoma. Three approaches exist
      abroad continents. In France and Europe, perioperative chemotherapy and
      gastrectomy with D1.5 lymph-node dissection is the current standard. In Japan and
      South Korea, postoperative adjuvant chemotherapy after surgery with D2 lymph-node
      dissection is the standard treatment. In the United States, where limited lymph
      node dissection is frequently performed, adjuvant chemoradiotherapy after surgery
      is the standard treatment. In France, postoperative chemoradiotherapy indications
      are discussed in limited settings: patients with locally advanced gastric cancer
      or lymph node involvement discovered on the pathologic report of the gastrectomy
      without preoperative chemotherapy delivery or in case of non-carcinologic
      resection (R1). Exclusive chemoradiotherapy can be proposed in patients unfit for
      surgery.

PMID- 30195981
TI  - [Implementation of experience feedback committees meetings between the
      radiotherapy centres of Northern France by the regional oncology network].
AB  - Onco, the Regional oncology network of Northern France, in partnership with
      Cronor, is piloting a project to harmonize radiotherapy practice. In 2016, a
      working party "Quality in Radiotherapy" was set up to encourage all centres in
      the network to participate in regional experience feedback committees. These
      committee meetings allow for analysis and handling of adverse events in
      radiotherapy within predefined areas of expertise. The purpose is to formalize
      and issue recommendations based on good practice by the use of regional
      bulletins. This article details how such experiential feedback committees are
      implemented, what they can contribute and the barriers to such work at each stage
      of the project.

PMID- 30195983
TI  - An architecture of open-source tools to combine textual information extraction,
      faceted search and information visualisation.
AB  - This article presents our steps to integrate complex and partly unstructured
      medical data into a clinical research database with subsequent decision support.
      Our main application is an integrated faceted search tool, accompanied by the
      visualisation of results of automatic information extraction from textual
      documents. We describe the details of our technical architecture (open-source
      tools), to be replicated at other universities, research institutes, or
      hospitals. Our exemplary use cases are nephrology and mammography. The software
      was first developed in the nephrology domain and then adapted to the mammography
      use case. We report on these case studies, illustrating how the application can
      be used by a clinician and which questions can be answered. We show that our
      architecture and the employed software modules are suitable for both areas of
      application with a limited amount of adaptations. For example, in nephrology we
      try to answer questions about the temporal characteristics of event sequences to
      gain significant insight from the data for cohort selection. We present a
      versatile time-line tool that enables the user to explore relations between a
      multitude of diagnosis and laboratory values.

PMID- 30195982
TI  - [Reference bases of radiotherapy under stereotaxic conditions for
      bronchopulmonary, hepatic, prostatic, upper aero-digestive, cerebral and bone
      tumors or metastases].
AB  - Since decades, stereotactic radiotherapy has spread out worldwide. Published
      results are very numerous. To clarify obviousness among all the publications,
      this recommendation review was written. Voluntarily, authors limited analysis of
      international best evidence literature on malignant tumors of lung, liver,
      prostate, head and neck, and metastasis of bone and brain. These data could be
      used to advance standardization and quality improvement of treatments performed
      in the nationwide radiotherapy departments and can provide useful guidance for
      centers worldwide.

PMID- 30195984
TI  - Deep convolutional neural networks for brain image analysis on magnetic resonance
      imaging: a review.
AB  - In recent years, deep convolutional neural networks (CNNs) have shown record
      shattering performance in a variety of computer vision problems, such as visual
      object recognition, detection and segmentation. These methods have also been
      utilised in medical image analysis domain for lesion segmentation, anatomical
      segmentation and classification. We present an extensive literature review of CNN
      techniques applied in brain magnetic resonance imaging (MRI) analysis, focusing
      on the architectures, pre-processing, data-preparation and post-processing
      strategies available in these works. The aim of this study is three-fold. Our
      primary goal is to report how different CNN architectures have evolved, discuss
      state-of-the-art strategies, condense their results obtained using public
      datasets and examine their pros and cons. Second, this paper is intended to be a
      detailed reference of the research activity in deep CNN for brain MRI analysis.
      Finally, we present a perspective on the future of CNNs in which we hint some of
      the research directions in subsequent years.

PMID- 30195985
TI  - Evaluation of the Tinetti score and fall risk assessment via accelerometry-based
      movement analysis.
AB  - Gait and balance disorders are among the main predisposing factors of falls in
      elderly. Clinical scales are widely employed to assess the risk of falling, but
      they require trained personnel. We investigate the use of objective measures
      obtained from a wearable accelerometer to evaluate the fall risk, determined by
      the Tinetti clinical scale. Seventy-nine patients and eleven volunteers were
      enrolled in two rehabilitation centers and underwent a full Tinetti test, while
      wearing a triaxial accelerometer at the chest. Tinetti scores were assessed by
      expert physicians and those subjects with a score <=18 were considered at high
      risk. First, we analyzed 21 accelerometer features by means of statistical tests
      and correlation analysis. Second, one regression and one classification problem
      were designed and solved using a linear model (LM) and an artificial neural
      network (ANN) to predict the Tinetti outcome. Pearson's correlation between the
      Tinetti score and a subset of 9 features (mainly related with standing and
      walking) was 0.71. The misclassification error of high risk patient was 0.21 and
      0.11, for LM and ANN, respectively. The work might foster the development of a
      new generation of applications meant to monitor the time evolution of the fall
      risk using low cost devices at home.

PMID- 30195986
TI  - Investigation of a New Couples Intervention for Individuals with Brain Injury: A
      Randomized Controlled Trial.
AB  - OBJECTIVE: This study aimed to (1) examine the efficacy of a treatment to enhance
      a couple's relationship after brain injury (BI) particularly in relationship
      satisfaction and communication; and (2) determine couples' satisfaction with this
      type of intervention. DESIGN: Randomized Wait-list Controlled (WC) Trial.
      SETTING: Midwestern outpatient BI rehabilitation center. INTERVENTION: The
      Couples CARE intervention is a 16 week, 2-hour, manualized small group treatment
      utilizing psychoeducation, affect recognition and empathy training, cognitive and
      dialectical behavioral treatments (CBT, DBT), communication skills training, and
      Gottman's theoretical framework for couples. PARTICIPANTS: Forty-four
      participants (22 persons with BI and their intimate partner) were randomized by
      couples to the intervention or WC group, with 11 couples in each group. MAIN
      OUTCOME MEASURES: Dyadic Adjustment Scale (DAS); Quality of Marriage Index (QMI);
      4 Horsemen of the Apocalypse communication questionnaire. Measures were completed
      by the person with BI and their partner at 3 time points: baseline, immediate
      post-intervention, 3-month follow-up. RESULTS: The experimental group showed
      significant improvement at post-test and follow-up on the DAS and the Horsemen
      questionnaire compared to baseline and to the WC group which showed no
      significant changes on these measures. No significant effects were observed on
      the QMI for either group. Satisfaction scores were largely favorable. CONCLUSION:
      suggest this intervention can improve couples' dyadic adjustment and
      communication after BI. High satisfaction ratings suggest this small group
      intervention is feasible with couples following BI. Future directions for this
      intervention are discussed.

PMID- 30195988
TI  - Preface.

PMID- 30195987
TI  - The TBI-CareQOL Measurement System: Development and Preliminary Validation of
      Health-Related Quality of Life Measures for Caregivers of Civilians and Service
      Members/Veterans With Traumatic Brain Injury.
AB  - OBJECTIVE: To develop a new measurement system, the Traumatic Brain Injury
      Caregiver Quality of Life (TBI-CareQOL), that can evaluate both general and
      caregiving-specific aspects of health-related quality of life (HRQOL) in
      caregivers of persons with traumatic brain injury (TBI). DESIGN: New item pools
      were developed and refined using literature reviews, qualitative data from focus
      groups, and cognitive debriefing with caregivers of civilians and service
      members/veterans with TBI, as well as expert review, reading level assessment,
      and translatability review; existing item banks and new item pools were assessed
      using an online data capture system. Exploratory and confirmatory factor
      analysis, item response theory, and differential item functioning analyses were
      utilized to develop new caregiver-specific item banks. Known-groups validity was
      examined using a series of independent samples t tests comparing caregivers of
      low-functioning vs high-functioning persons with TBI for each of the new
      measures, as well as for 10 existing Patient-Reported Outcomes Measurement
      Information System (PROMIS) measures. SETTING: Three TBI Model Systems
      rehabilitation hospitals, an academic medical center, and a military medical
      treatment facility. PARTICIPANTS: Caregivers (N=560) of civilians (n=344) or
      service members/veterans with TBI (n=216). INTERVENTIONS: Not applicable. MAIN
      OUTCOME MEASURES: The TBI-CareQOL measurement system (including 5 new measures
      and 10 existing PROMIS measures). RESULTS: Exploratory and confirmatory factor
      analysis, item response theory, and differential item functioning analyses
      supported the development of 5 new item banks for Feelings of Loss-Self, Feelings
      of Loss-Person with TBI, Caregiver-Specific Anxiety, Feeling Trapped, and
      Caregiver Strain. In support of validity, individuals who were caring for low
      functioning persons with TBI had significantly worse HRQOL than caregivers that
      were caring for high-functioning persons with TBI for both the new caregiver
      specific HRQOL measures, and for the 10 existing PROMIS measures. CONCLUSIONS:
      The TBI-CareQOL includes both validated PROMIS measures and newly developed
      caregiver-specific measures. Together, these generic and specific measures
      provide a comprehensive assessment of HRQOL for caregivers of civilians and
      service members/veterans with TBI.

PMID- 30195989
TI  - What are the goals of prenatal genetic testing?
AB  - The landscape of genetic testing and screening has changed tremendously since the
      initial description of the molecular structure of DNA. Given this, it is critical
      that providers reflect on the goals of prenatal screening and diagnostic testing,
      and how these tests impact perinatal outcomes. The participants of this workshop
      were in agreement that the goal of prenatal genetic testing should be focused on
      improving outcomes for women and families. While prenatal testing has
      historically focused on the option for pregnancy termination, increasing numbers
      of prenatal and perinatal treatments are available. As more in utero therapies
      are developed, the detection of disorders that are amenable to, and would benefit
      from, prenatal or immediate neonatal targeted therapy will increasingly be a
      focus of prenatal testing. Prenatal genetic testing must also balance the ethical
      principles of autonomy and distributive justice. The workshop participants agreed
      that stakeholders such as medical professionals, professional societies,
      insurers, commercial laboratories, and the public should consider and come to
      agreement regarding the appropriate objectives for and use of these tests.

PMID- 30195990
TI  - Psychophysical evaluation of contrast sensitivity using Gabor patches in tobacco
      addiction.
AB  - This study, an extension of Fernandes et al. (2017), provided consistent contrast
      sensitivity function (CSF) measurements in a large sample. CSF was assessed for
      luminance stimuli in different 48 chronic smokers and 50 healthy nonsmokers.
      Stimuli for the CSF were Gabor patches with spatial frequencies of .2, 2.5, 5.0,
      10.0, and 20.0 cycles per degree (cpd). The use of Gabor patches minimizes
      uncertainty in spatial position and detection of frequencies. The Gabor patches
      consisted of vertical gratings that were multiplied by a two-dimensional spatial
      Gaussian envelope. All of the groups were matched for gender and level of
      education. All of the participants were free from any neurological disorder,
      cardiovascular disease, and identifiable ocular disease, and they had normal or
      corrected-to-normal visual acuity. No abnormalities were detected on the
      fundoscopic examination or optical coherence tomographic examination. The smoker
      group had a lower CSF compared with healthy nonsmokers at all spatial
      frequencies. These results indicate that cigarette smoking or chronic exposure to
      its constituent compounds affects early-stage visual discrimination, suggesting
      the existence of deficits in early visual spatial processing in smokers.

PMID- 30195991
TI  - New Perspectives on the Pathogenesis of PCOS: Neuroendocrine Origins.
AB  - Polycystic ovary syndrome (PCOS) is the most common endocrine condition in
      reproductive-aged women. It is characterized by reproductive, endocrine,
      metabolic, and psychological features. The cause of PCOS is unknown, thus there
      is no cure and its management remains suboptimal because it relies on the ad hoc
      empirical management of symptoms only. We review here the strong support for PCOS
      having a neuroendocrine origin. In particular, we focus on the role of aberrant
      hypothalamic-pituitary function and associated hyperandrogenism, and their role
      as major drivers of the mechanisms underpinning the development of PCOS. This
      important information now provides a target site and a potential mechanism for
      the future development of novel, targeted, and mechanism-based effective
      therapies for the treatment of PCOS.

PMID- 30195992
TI  - The contribution of atmospheric particulate matter to the formation of CX3R-type
      disinfection by-products in rainwater during chlorination.
AB  - Atmospheric particulate matter (PM) can be scavenged by rainfall and contribute
      dissolved organic matter (DOM) to rainwater. Rainwater may serve as a part or the
      whole of drinking water sources, leading to the introduction of PM-derived DOM
      into drinking water. However, little information is available on the role of PM
      derived DOM as a remarkable precursor of CX3R-type disinfection by-products
      (DBPs) in rainwater. In this study, samples were collected from ten occurrences
      of rainfall in Shanghai and batch experiments were executed to explore the
      contribution of PM-derived DOM to CX3R-type DBP formation in rainwater and to
      further understand some of unknowns regarding its characteristics. Results
      revealed that a part of PM was scavenged by rainfall and the scavenge performance
      was better for smaller PM. The formation potentials (FPs) of individual CX3R-type
      DBP were similar among size-isolated PM. TCM was predominant (around 0.5-4.5 MUg
      C/mg-C) and TCAA was the secondary (around 0.6-3.2 MUg-C/mg-C) among all
      detectable CX3R-type DBPs. Based on the PM removal data and DBP FP results, the
      contribution of PM-derived DOM to CX3R-type DBP formation in rainwater was
      modeled. Furthermore, aromatic proteins and soluble microbial product-like
      compounds were found to be significant compositions, which were reported to be
      DBP precursors. And low molecular weight (< 10 kDa) DOM derived from total PM and
      rainwater exhibited higher CX3R-type DBP FPs. DOM fractions with higher SUVA254
      and SUVA285 values gave relatively higher yields of CX3R-type DBPs, indicating
      that aromatic compounds played an important role in DBP formation.

PMID- 30195993
TI  - Investigation of backwashing effectiveness in membrane bioreactor (MBR) based on
      different membrane fouling stages.
AB  - In this study the effect of different fouling stages of hollow fiber membranes on
      effective backwashing length in MBR has been investigated. Computational fluid
      dynamics (CFD) is imported to simulate backwashing process. A multi-physics
      coupling model for free porous media flow, convective mass transfer and diluted
      species transport was established. The laser bijection sensors (LBS) were
      imported to monitor the backwashing solution position inside fiber lumen.
      Simulation results indicated that membrane fouling degree could change the
      velocity of backwash solution inside fiber lumen and make a further effect on
      effective backwash length. The signal variations of LBS are in accordance with
      the simulation results. The backwashing process can only play an active role when
      the filtration pressure is below the critical TMP. It can be concluded that
      backwash duration in industrial applications need to be set based on changes in
      TMP.

PMID- 30195994
TI  - Corrections.

PMID- 30195995
TI  - Deliberations of the Strategic Advisory Group of Experts on Immunization on the
      use of CYD-TDV dengue vaccine.
AB  - The Strategic Advisory Group of Experts (SAGE) on Immunization advises WHO on
      global policies for vaccines. In April, 2016, SAGE issued recommendations on the
      use of the first licenced dengue vaccine, CYD-TDV. In November, 2017, a
      retrospective analysis of clinical trial data, stratifying participants according
      to their dengue serostatus before the first vaccine dose, showed that although in
      high seroprevalence settings the vaccine provides overall population benefit,
      there was an excess risk of severe dengue in seronegative vaccinees. SAGE's
      working group on dengue vaccines met to discuss the new data and mainly
      considered two vaccination strategies: vaccination of populations with dengue
      seroprevalence rates above 80% or screening of individuals before vaccination,
      and vaccinating only seropositive individuals. We report on the deliberations
      that informed the recommendation of the pre-vaccination screening strategy, in
      April, 2018. Important research and implementation questions remain for CYD-TDV,
      including the development of a highly sensitive and specific rapid diagnostic
      test to determine serostatus, simplified immunisation schedules, and assessment
      of the need for booster doses.

PMID- 30195997
TI  - Back to chloroquine for malaria prophylaxis in pregnancy?

PMID- 30195998
TI  - The Rise of Cotton Genomics.
AB  - Cotton is the most important fiber crop, but its polyploid genome is complex and
      difficult to improve. Recent advances in obtaining high-quality genome sequences
      of cultivated tetraploid and diploid cotton species may now overcome this hurdle,
      as well as provide new insights on important fiber quality and disease resistance
      genes.

PMID- 30195996
TI  - Chloroquine as weekly chemoprophylaxis or intermittent treatment to prevent
      malaria in pregnancy in Malawi: a randomised controlled trial.
AB  - BACKGROUND: Sulfadoxine-pyrimethamine resistance threatens efficacy of
      intermittent preventive treatment of malaria during pregnancy, and alternative
      regimens need to be identified. With the return of chloroquine efficacy in
      southern Africa, we postulated that chloroquine either as an intermittent therapy
      or as weekly chemoprophylaxis would be more efficacious than intermittent
      sulfadoxine-pyrimethamine for prevention of malaria in pregnancy and associated
      maternal and newborn adverse outcomes. METHODS: We did an open-label, single
      centre, randomised controlled trial at Ndirande Health Centre, Blantyre, in
      southern Malawi. We enrolled pregnant women (first or second pregnancy) at 20-28
      weeks' gestation who were HIV negative. Participants were randomly assigned in a
      1:1:1 ratio using a computer-generated list to either intermittent sulfadoxine
      pyrimethamine (two doses of 1500 mg sulfadoxine and 75 mg pyrimethamine, 4 weeks
      apart), intermittent chloroquine (two doses of 600 mg on day 1, 600 mg on day 2,
      and 300 mg on day 3), or chloroquine prophylaxis (600 mg on day 1 then 300 mg
      every week). The primary endpoint was placental malaria in the modified intent-to
      treat population, which consisted of participants who contributed placental
      histopathology data at birth. Secondary outcomes included clinical malaria,
      maternal anaemia, low birthweight, and safety. This trial is registered with
      ClinicalTrials.gov, number NCT01443130. FINDINGS: Between February, 2012, and
      May, 2014, we enrolled and randomly allocated 900 women, of whom 765 contributed
      histopathological data and were included in the primary analysis. 108 (14%) women
      had placental malaria, which was lower than the anticipated prevalence of
      placental malaria infection. Protection from placental malaria was not improved
      by chloroquine as either prophylaxis (30 [12%] of 259 had positive
      histopathology; relative risk [RR] 0.75, 95% CI 0.48-1.17) or intermittent
      therapy (39 [15%] of 253; RR 1.00, 0.67-1.50) compared with intermittent
      sulfadoxine-pyrimethamine (39 [15%] of 253). In protocol-specified analyses
      adjusted for maternal age, gestational age at enrolment, bednet use the night
      before enrolment, anaemia at enrolment, and malaria infection at enrolment, women
      taking chloroquine as prophylaxis had 34% lower placental infections than did
      those allocated intermittent sulfadoxine-pyrimethamine (RR 0.66, 95% CI 0.46
      0.95). Clinical malaria was reported in nine women assigned intermittent
      sulfadoxine-pyrimethamine, four allocated intermittent chloroquine (p=0.26), and
      two allocated chloroquine prophylaxis (p=0.063). Maternal anaemia was noted in
      five women assigned intermittent sulfadoxine-pyrimethamine, 15 allocated
      intermittent chloroquine (p=0.038), and six assigned chloroquine prophylaxis
      (p>0.99). Low birthweight was recorded for 31 babies born to women allocated
      intermittent sulfadoxine-pyrimethamine, 29 assigned intermittent chloroquine
      (p=0.78), and 41 allocated chloroquine prophylaxis (p=0.28). Four women assigned
      intermittent sulfadoxine-pyrimethamine had adverse events possibly related to
      study product compared with 94 women allocated intermittent chloroquine
      (p<0.0001) and 26 allocated chloroquine prophylaxis (p<0.0001). Three women had
      severe or life-threatening adverse events related to study product, of whom all
      were assigned intermittent chloroquine (p=0.25). INTERPRETATION: Chloroquine
      administered as intermittent therapy did not provide better protection from
      malaria and related adverse effects compared with intermittent sulfadoxine
      pyrimethamine in a setting of high resistance to sulfadoxine-pyrimethamine.
      Chloroquine chemoprophylaxis might provide benefit in protecting against malaria
      during pregnancy, but studies with larger sample sizes are needed to confirm
      these results. FUNDING: US National Institutes of Health.

PMID- 30195999
TI  - Mutagenicity assessment of environmental contaminations in a hospital centralized
      reconstitution unit.
AB  - INTRODUCTION: Cytotoxic drug exposure of hospital staff preparing intravenous
      chemotherapy is a major issue and related mutagenic risks should be more
      explored. The aim of this study was to assess the mutagenicity of several
      cytotoxic mixtures prepared at fixed concentrations, and the mutagenicity of
      environmental samples collected in a hospital centralized reconstitution unit. In
      parallel cytotoxic exposure in environmental samples was quantified. METHODS:
      Environmental samples were performed by wiping method using swabs in five
      critical production unit areas. Mutagenicity was assessed with a liquid
      microplate AMES test using two salmonella typhimurium strains (TA98 and TA100),
      in prepared cytotoxic mixtures containing 14 cytotoxic drugs (cyclophosphamide,
      cytarabine, dacarbazine, docetaxel, doxorubicin, epirubicin, etoposide, 5
      fluorouracil, gemcitabine, ifosfamide, irinotecan, methotrexate, paclitaxel and
      pemetrexed) according a dichotomous strategy and in environmental samples.
      Cytotoxic drugs were quantified in samples using liquid chromatography coupled to
      mass tandem spectrometry. RESULTS: Mutagenesis was observed for the mix of 14
      cytotoxic drugs with TA98 strain +/- S9 fraction but not TA100 strain. After
      dichotomous approach, only doxorubicin and epirubicin exposure were associated to
      mutagenesis. The mutagenesis observed was expressed at lower concentrations with
      the mix of the 14 drugs than with anthracyclins alone, assuming a synergistic
      effect. Despite measurable level of cytotoxic contamination in environmental
      samples, no mutagenesis was highlighted in Ames tests performed on these
      environmental samples. CONCLUSIONS: The analyses carried out show the
      conservation of the mutagenicity of cytotoxic drugs found in very low quantities
      in the environment. The traces of cytotoxic drugs found in our unit regularly
      exceed the limits given by some authors. This approach may be considered as a new
      tool to monitor environmental contamination by cytotoxic drugs.

PMID- 30196000
TI  - Characterization of microbial communities of soils from gold mine tailings and
      identification of mercury-resistant strain.
AB  - To enrich the understanding of the complex environmental system of soil and
      microorganisms in gold tailings, we studied the effects of environmental factors
      on the microbial community diversity in gold mine tailing soil in Beijing, and
      the strains screened from the soil with serious mercury (Hg) pollution. The
      results showed that microbial diversity and community composition varied among
      sites, and at varying depths, soil microbes were significantly affected by soil
      environmental factors such as lead (Pb), Hg, pH, and total organic carbon (TOC).
      Pb and Hg negatively affected soil microbial diversity, and less-polluted soil
      showed increased microbial diversities and complex community structure. Community
      composition analysis showed that Firmicutes, Proteobacteria and Actinobacteria
      were the dominant microorganisms. Moreover, Hg-resistant bacterial species
      isolated from soil samples were identified as Pseudomonas plecoglossicida with a
      high Hg tolerance efficiency. This study is important in understanding the
      microbial diversity and function in gold mine tailing soils and can widen the
      application for bioremediation process.

PMID- 30196001
TI  - Elucidation of endocrine-disrupting polychlorinated biphenyls binding potency
      with steroidogenic genes: Integration of in silico methods and ensemble docking
      approaches.
AB  - A myriad of polychlorinated biphenyls (PCBs) may have potential to reproductive
      axis and endocrine disruptions. PCBs mostly breach the cholesterol
      biotransformation in mitochondria through interfering with steroidogenic genes
      and lead to adverse consequences in steroidogenesis; however, studies are scanty.
      In this examination, the combinations of quantitative structure-activity
      relationship (QSAR) modeling and ensemble docking approaches was performed to
      envisage structural properties of PCBs that influence the developmental toxicity,
      estrogen receptor-mediated impacts, and to provide a better comprehension of
      binding levels between PCBs, steroidogenic acute regulatory protein (StAR) and
      cholesterol side-chain cleavage enzyme (CYP11A1). Prognostic QSAR models were
      illustrated with good robustness and predictive ability. Models provide extensive
      data on applicability domain and similarities between PCBs and training set
      compounds was used to implement for clustering and classification of toxic PCBs
      by employing Self-Organizing Maps. Docking and interaction profiles
      interpretations provided various insights into the structural features of PCBs
      that influence the cholesterol binding to StAR and CYP11A1 domains. The non
      polar, atomic pi - stacking and halogen bonds of PCBs with novel hotspots
      residues of StAR and CYP11A1 was indicated subtle conformational changes that
      barrier to cholesterol binding and/or locks to cholesterol ejection from Omega1
      loop of StAR, and inhibits cholesterol to pregnenolone biosynthesis by CYP11A1;
      thus, these are probably revealed as block-cluster mechanisms. These outcomes are
      potential to be useful to predict developmental toxicity, endocrine disruption
      potencies and anti-steroidogenic activities of other environmental pollutants and
      provided sorted pinpoints for further evaluation of interaction mechanisms of
      PCBs with other sterodogenic genes.

PMID- 30196002
TI  - Boron increases root elongation by reducing aluminum induced disorganized
      distribution of HG epitopes and alterations in subcellular cell wall structure of
      trifoliate orange roots.
AB  - Aluminum toxicity limits the plant growth by inducing inhibition of root
      elongation. Although several mechanisms have been proposed regarding the
      phytotoxic effects of aluminum on inhibition of root elongation; the primary
      causes of aluminum induced root inhibition and its mitigation by boron (B) are
      still elusive. The present study was carried out to explore the mechanisms of B
      induced mitigation of aluminum toxicity and to investigate the changes in well
      wall structure under aluminum toxicity coupled with the techniques of confocal
      laser microscope, lumogallion and transmission electron microscope. The results
      revealed that aluminum toxicity severely hampered the root elongation and plant
      biomass. Moreover, alteration in subcellular structure were observed under
      aluminum toxicity, however, such negative effects were further exacerbated with B
      deficiency. Aluminum toxicity indicated disorganized distribution of HG
      (homogalacturonan) epitopes with higher accumulation of apoplastic aluminum.
      Nevertheless, B supply improved root elongation, and reduced the aluminum uptake.
      Taken together, it is concluded that B application can reduce aluminum toxicity
      and improve root elongation by decreasing Al3+ accumulation to cell wall,
      alteration in the cell wall structure and reducing the distribution of HG
      epitopes in the roots of trifoliate (Poncirus trifoliate) orange.

PMID- 30196003
TI  - Alginate-modified biochar derived from Ca(II)-impregnated biomass: Excellent anti
      interference ability for Pb(II) removal.
AB  - A novel biochar modified with sodium alginate was prepared using Ca(II)
      impregnated biomass, and used to remove metals from aqueous solutions. The
      maximum adsorption capacity for Pb(II) was estimated to be 1.225 mmol/g (253.6
      mg/g), which is far more than that of most adsorbents. Moreover, the modified
      biochar had a great anti-interference ability for effective removal of Pb(II)
      from multi-metal system. The biochar still had strong ability to adsorb Pb(II)
      when the initial concentrations of interfering ions were 5 times higher than that
      of Pb(II). Functional groups and minerals of the biochar worked for Pb(II)
      removal and the anti-interference ability. On the one hand, carboxyl could
      complex with Pb(II) through monodentate and bidentate bridging; on the other
      hand, Pb(II) was easier to form a precipitate with minerals than other metals.
      This study suggested that the novel biochar had the potential for practical
      application in effective removal of Pb(II) from wastewater.

PMID- 30196004
TI  - [Studies on the Interaction of Poly-L-lysine with Fibrinogen with Spectroscopic
      Methods].
AB  - Poly-L-lysine is an important polycation which has great prospect in the
      biomedical application. However, there are few reports on the blood compatibility
      of poly-L-lysine at present, especially the interaction between poly-L-lysine and
      some important proteins from the blood, which is studied with spectroscopic
      methods. Therefore, it is of certain innovation to further evaluate the blood
      compatibility of poly-L-lysine, which is studied by the interaction between poly
      L-lysine and fibrinogen with many spectroscopic methods. In this study, the
      fluorescence, ultraviolet visible and circular dichroism spectroscopy were used
      to research the effects of poly-L-lysine on the structure of fibrinogen. Briefly,
      zeta potential experiment showed that positive potential of poly-L-lysine
      increased with increasing concentration. Complexation experiment showed that 0.01
      mg.mL(-1) poly-L-lysine had little effect on the function of fibrinogen, and the
      interaction strengthened with concentration increasing. Fluorescence spectra
      showed that the fluorescence of fibrinogen was quenched in a concentration
      dependent way when the emission wavelength was 341 nm (lambdaem=341 nm).
      Ultraviolet visible spectra showed that the absorption intensity of fibrinogen at
      200~240 and 278 nm, which was less affected by 0.025 mg.mL(-1) poly-L-lysine,
      reduced with the concentration of poly-L-lysine increasing. Circular dichroism
      spectra showed when the concentration of poly-L-lysine increased, the effect of
      poly-L-lysine on the secondary structure of fibrinogen strengthened. Overall, as
      the concentration of poly-L-lysine increased, the alpha-helix content of
      fibrinogen decreased and the beta-fold, beta-turn and random coil content of
      fibrinogen increased. These results showed that the electrostatic interaction was
      occurred between poly-L-lysine and fibrinogen, which influenced the structure of
      fibrinogen by concentration dependence. While the effect of poly-L-lysine (0.01
      and 0.025 mg.mL(-1)) on fibrinogen was little, poly-L-lysine of high
      concentration would damage the physiological function of fibrinogen. Therefore,
      it is necessary to consider the concentration factor in the development and
      application of poly-L-lysine. In this study, a simple, convenient and systematic
      method is utilized to study the interaction between materials and fibrinogen
      which is helpful to evaluate the blood compatibility of materials sufficiently.
      Furthermore, the results of this study will provide important guiding information
      for the biomedical applications of poly-L-lysine.

PMID- 30196005
TI  - Microvascular reconstruction two years after subtotal glossectomy: Is it worth
      it?
AB  - We ought to report an unusual case of a 49-year-old patient who underwent delayed
      reconstruction of the oral cavity defect, with an anterolateral thigh flap, two
      years after surgical demolition and adjuvant chemo-radiotherapy. At the end of
      oncologic treatment, he could not eat through oral route and presented evident
      speech articulation difficulties. After surgical reconstruction, swallowing
      assessment showed an improvement of swallowing with no gross signs of airways
      inhalation. His understandability of speech improved as well. Delayed
      reconstruction by a microvascular free flap with exclusive functional
      rehabilitation intent is feasible and may have satisfactory functional outcomes.

PMID- 30196006
TI  - A well-tolerated and rapidly acting thiopurine for IBD?
AB  - Thiopurine drugs continue to be a cornerstone of inflammatory bowel disease (IBD)
      treatment. Thiopurines are economical compared with many newer medical treatments
      for IBD, other chronic inflammatory diseases and leukaemia, although they are not
      without their shortcomings. These include a slow-onset therapeutic action and
      many adverse drug reactions. This feature article surveys published data,
      unpublished in vitro and in vivo experiments, as well as clinical experience,
      underpinning a rationale for bringing a novel thiopurine drug formulation to
      market. This formulation has a rapid action making it suitable for the induction
      and maintenance treatment of IBD and avoids most thiopurine-associated adverse
      reactions.

PMID- 30196007
TI  - M2 macrophage subset decrement is an indicator of bleeding tendency in pediatric
      dengue disease.
AB  - BACKGROUND/PURPOSE: Dengue disease is widespread in tropical and sub-tropical
      regions. Severe dengue infection is characterized by plasma leakage, fluid
      accumulation, severe bleeding, or vital organ impairment. Bleeding is a critical
      complication of dengue disease. However, the biomarkers of dengue disease are
      still unknown. Macrophages have a distinct polarization phenotype related to
      M1/M2 classification. Macrophage polarization toward the pro-inflammatory M1
      phenotype is considered critical for efficient antiviral immune responses,
      whereas the anti-inflammatory M2 phenotype is considered essential for tissue
      remodeling. We investigated macrophage polarization patterns in the peripheral
      blood of pediatric patients with dengue disease. METHODS: Medical records and
      laboratory data were collected from 23 pediatric healthy controls and 100 dengue
      disease samples from 50 dengue patients. Macrophage polarization-related surface
      markers were assessed using flow cytometry. RESULTS: The percentage of
      macrophages in the peripheral blood was higher in dengue patients than in the
      healthy controls. The percentages of M2a and M2c macrophage subsets were higher
      and the percentage of M1 macrophage subset was lower in dengue patients than in
      healthy controls. However, the percentages of M1, M2a and M2b macrophage subsets
      in dengue patients with bleeding tendency were lower than that without bleeding
      tendency. The percentages of M2a, M2b, and M2c macrophage subsets were positively
      correlated with platelet counts. CONCLUSION: Decreased the percentages of M2
      macrophage subsets in pediatric dengue patients are associated with bleeding
      tendency and lower platelet counts.

PMID- 30196008
TI  - Roles of lysophosphatidic acid and sphingosine-1-phosphate in stem cell biology.
AB  - Stem cells are unique in their ability to self-renew and differentiate into
      various cell types. Because of these features, stem cells are key to the
      formation of organisms and play fundamental roles in tissue regeneration and
      repair. Mechanisms controlling their fate are thus fundamental to the development
      and homeostasis of tissues and organs. Lysophosphatidic acid (LPA) and
      sphingosine-1-phosphate (S1P) are bioactive phospholipids that play a wide range
      of roles in multiple cell types, during developmental and pathophysiological
      events. Considerable evidence now demonstrates the potent roles of LPA and S1P in
      the biology of pluripotent and adult stem cells, from maintenance to repair. Here
      we review their roles for each main category of stem cells and explore how those
      effects impact development and physiopathology.

PMID- 30196009
TI  - Enhanced production of d-lactate from mixed sugars in Corynebacterium glutamicum
      by overexpression of glycolytic genes encoding phosphofructokinase and
      triosephosphate isomerase.
AB  - The use of mixed sugars containing glucose and xylose in lignocellulosic biomass
      is desirable for the microbial production of chemicals and fuels. We investigated
      the effect of individual or simultaneous overexpression of glycolytic genes on d
      lactate production from a mixture of glucose and xylose by a recombinant xylose
      assimilating Corynebacterium glutamicum strain. The individual overexpression of
      genes encoding phosphofructokinase (PFK) and triosephosphate isomerase (TPI)
      increased d-lactate production rate by 71% and 34%, respectively, with
      corresponding increases (2.4- and 1.8-fold) in the glucose consumption; however,
      the amount of xylose consumed not altered. d-Lactate yield was also increased by
      5.5%, but only in the strain overexpressing the gene encoding PFK. In the parent
      strain and the strains overexpressing the genes encoding PFK or TPI, a reduction
      in d-lactate production occurred at approximately 900 mM after 32 h. However, the
      strain that simultaneously overexpressed the genes encoding PFK and TPI continued
      to produce d-lactate after 32 h, with the eventual production of 1326 mM after
      production for 80 h in mineral salts medium. Our findings contribute to the cost
      effective, large-scale production of d-lactate from mixed sugars.

PMID- 30196010
TI  - Effect of cell therapy with allogeneic osteoblasts on bone repair of rat calvaria
      defects.
AB  - BACKGROUND AIMS: Regenerative medicine strategies based on cell therapy are
      considered a promising approach to repair bone defects. The aims of this study
      were to evaluate the effect of subculturing on the osteogenic potential of
      osteoblasts derived from newborn rat calvaria and the effect of these osteoblasts
      on bone repair of rat calvaria defects. METHODS: Cells were obtained from 50
      newborn rat calvaria, and primary osteoblasts (OB) were compared with first
      passage (OB-P1) in terms of osteogenic potential by assaying cell proliferation,
      alkaline phosphatase (ALP) activity, extracellular matrix mineralization and gene
      expression of the osteoblastic markers RUNX2, ALP, osteocalcin and bone
      sialoprotein. Then, 5-mm calvaria defects were created in 24 Wistar rats, and
      after 2 weeks, they were locally injected with 50 uL of phosphate-buffered saline
      containing either 5 * 106 osteoblasts (OB-P1, n = 12) or no cells (control, n =
      12). Four weeks post-injection, the bone formation was evaluated by micro
      computed tomography and histological analyses. Data were compared by analysis of
      variance, followed by the Student-Newman-Keuls's test or Student's t-test (P <=
      0.05). RESULTS: OB-P1 showed high proliferation and ALP activity, and despite the
      reduced gene expression of osteoblastic markers and extracellular matrix
      mineralization compared with OB, they displayed osteogenic potential, being a
      good choice for injection into calvaria defects. The micro-tomographic and
      histological data showed that defects treated with OB-P1 presented higher bone
      formation compared with control defects. DISCUSSION: Our results indicate that
      cells derived from newborn rat calvaria retain osteoblastic characteristics after
      subculturing and that these osteoblasts stimulate bone repair in a rat calvaria
      defect model.

PMID- 30196011
TI  - Functionalized glycolipids for potential bioconjugation of vesicles.
AB  - Two azide-terminated oligoethylene oxide spacered glycolipids have been
      synthesized, and their assembly behavior has been studied in comparison to the
      corresponding base surfactants. The results suggest potential of the Guerbet
      lactoside-based compound for targeted drug delivery, while a coiling of the
      ethylene oxide linker disfavors the application of the glucoside.

PMID- 30196012
TI  - High-risk HPV detection and associated cervical lesions in a population of French
      menopausal women.
AB  - BACKGROUND: With population ageing, post-menopausal women represent a new group
      to be considered in cervical cancer screening strategies, including the
      significance of High Risk (HR)-HPV detection. OBJECTIVES: A retrospective
      analysis was conducted in a cohort of 406 menopausal women attending routine
      gynaecological consultation at the Hospital of Montpellier (France). STUDY
      DESIGN: All women benefited from a cervical smear and HR-HPV detection using
      Hybrid Capture 2 (HC2) test. The prevalence of cytological abnormalities, HR-HPV
      detection and risk factors associated with HR-HPV detection were analyzed.
      Evolution of both tests was evaluated in a sub-group of women with adequate
      follow-up. RESULTS: Five women (1.2%) had an abnormal cervical smear at baseline.
      HR-HPV was detected in 40 women (9.9%), including 36 women with normal cytology
      (9%). Risk factors associated with HR-HPV detection at enrolment were a previous
      history of Cervical Intraepithelial Neoplasia and a high socio-economic level,
      but not hormone replacement therapy. When cytology and HR-HPV detection were
      negative at enrolment, both remained negative for 95% (230/241) of women during
      follow-up (median duration of follow-up: 60 months). HR-HPV persistence was
      observed for 55% (18/33) of women with normal cytology and positive HR-HPV test.
      Finally, all women with a final diagnosis of high-grade (CIN2+) cervical lesion
      (N = 7) had a positive HR-HPV test with or without abnormal cytology.
      CONCLUSIONS: HR-HPV was detected in 9.9% of menopausal women. HR-HPV detection
      was a better predictor of CIN2+ lesions than cytology in this population. Women
      with previous CIN history should benefit from HR-HPV testing and need long term
      follow-up.

PMID- 30196013
TI  - The association between human papillomavirus 16, 18 DNA load and E6 protein
      expression in cervical intraepithelial neoplasia and cancer.
AB  - BACKGROUND: It has been reported that high HPV DNA load and elevated E6 protein
      expression correlate with cervical cancer, but no epidemiological study has been
      performed. OBJECTIVES: To assess the association between type-specific HPV DNA
      load and presence of E6 protein in cervical intraepithelial neoplasia and cancer.
      STUDY DESIGN: This study was a cross-sectional multicenter study performed
      between 2013 and 2017. A total of 1717 women (normal histopathology: n = 916;
      CIN1: n = 94; CIN2: n = 63; CIN3: n = 130; SCC: n = 474; adenocarcinoma: n = 40)
      were included. HPV DNA load and presence of E6 protein were detected. DNA load
      was measured as log copies/10,000 cells. RESULTS: The HPV16/18-E6 positivity
      rates increased from negative for DNA to the highest load grade. Compared to the
      HPV16 DNA negatives, women with low (RR = 31.5, 95%CI = 18.9-52.5), medium-low
      (RR = 133.5, 95%CI = 77.3-230.7), medium-high (RR = 247.9, 95%CI = 134.9-455.6)
      and high DNA loads (RR = 677.9, 95%CI = 301.6-1523.7) had increasingly higher
      relative ratios of HPV16-E6 expression. The association of HPV18-E6 with its DNA
      load was also significant for low (RR = 27.9, 95%CI = 10.4-74.9), medium-low (RR
      = 89.0, 95%CI = 32.8-241.3), medium-high (RR = 276.8, 95%CI = 76.7-998.9) and
      high grade (RR = 441.2, 95%CI = 97.7-1992.4). The positivity rates of both HPV16
      DNA and E6 protein increased consistently with the severity of diseases from
      normal histopathology to SCC. Unlike HPV16, the trends of HPV18 DNA and E6
      protein fluctuated consistently among women from normal histopathology to cancer.
      DNA load in E6-positive women was significantly higher than E6-negative for both
      types. CONCLUSIONS: There is a type-dependent association between HPV16/18 DNA
      load and E6 protein; our study furthers the understanding of the natural history
      of cervical cancer.

PMID- 30196014
TI  - Cell-seeded 3D scaffolds as in vitro models for electroporation.
AB  - Electroporation of cells is usually studied using cell suspensions or monolayer
      cultures. 3D scaffolds for cell culture have been recently designed in order to
      reproduce in vitro the complex and multifactorial environment experimented in
      vivo by cells. In fact, it is well known that 2D cell cultures are not able to
      simulate the complex interactions between the cells and their extracellular
      matrix (ECM). Recently, some examples of 3D models, like spheroids, have been
      investigated also in the electroporation field. Spheroids have been proposed in
      electrochemotherapy (ECT) studies to mimic tumor in vivo conditions: they are
      easy-to-handle 3D models but their sensitivity to electric field pulses depends
      from their diameter and, more interestingly, despite being relevant for
      intercellular junctions, they are not so much so for cell-ECM interactions. In
      this work, we propose a 3D macroscopic myxoid matrix for cell culture that would
      mimic the in vivo environment of myxoid stroma tumors. The myxoid stroma consists
      of abundant basic substances with large amounts of glycosaminoglycans (hyaluronic
      acid) and proteoglycans, poor collagen fibers and no elastin content. In the
      proposed approach, tumor cells seeded on 3D scaffolds mimic of myxoid stroma can
      establish both cell-cell and cell-ECM 3D interactions. The MCF7 cells (human
      breast adenocarcinoma cell line) were seeded in complete culture medium. Cell
      cultures were incubated at 37  degrees C for either 24 h, 3 days or 7 day. Some
      samples were used to assess cell vitality using 3-(4,5-dimethylthiazolyl-2)-2,5
      diphenyltetrazolium bromide (MTT) test and others for electroporation tests and
      for histopathological analysis. The electroporation has been verified by the
      fluorescent dye Propidium cellular uptake. The proposed myxoid stroma scaffold
      induces cell proliferation and shows fibrous structures produced by cells, the
      concentration of which increases with culture time. The proposed matrix will be
      used for further investigations as a new scaffold for cell culture. Tumor cells
      grown into these new scaffolds will be used to evaluate electroporation including
      the stroma effect.

PMID- 30196015
TI  - Towards the integrative analysis of tick microbiome.

PMID- 30196016
TI  - Retrospective study of epidemiological, clinical and pathological findings of
      bovine babesiosis in Mato Grosso do Sul, Brazil (1995 -2017).
AB  - Babesiosis is a tick-borne hemolytic disease caused by intraerythrocytic
      protozoan parasites of the genus Babesia. The present study describes
      epidemiological, clinical, and pathological features of cases of bovine
      babesiosis diagnosed over the last two decades in the state of Mato Grosso do Sul
      in central-western Brazil. Examination of a total of 5298 bovine samples resulted
      in a definitive or presumptive diagnosis of babesiosis in 41 cases from 33
      outbreaks. Babesia bovis was the most common causal agent of bovine babesiosis,
      and animals of all ages were affected. Zebu cattle, which are more frequent in
      the study region than are taurine cattle, were the cattle most often affected.
      Although zebu cattle have been claimed to be highly tolerant, the present
      findings show that they can develop severe illness and die due to Babesia spp.
      infection. The disease was diagnosed almost every year over the time period
      covered in this study (1995-2017). However, the number of cases of bovine
      babesiosis diagnosed was low compared to the total number of cases reviewed.
      Veterinary practitioners that work on cattle farms should to be able to diagnose
      the disease in its early stages so that treatment can be initiated promptly and
      economic losses can be minimized.

PMID- 30196017
TI  - Surgical considerations for neonates with necrotizing enterocolitis.
AB  - Necrotizing enterocolitis (NEC) is a potentially devastating condition that
      preferentially affects premature and low birth weight infants, with approximately
      half requiring acute surgical intervention. Surgical consult should be considered
      early on, and deterioration despite maximal medical therapy or the finding of
      pneumoperitoneum are the strongest indications for emergent surgical
      intervention. There is no clear consensus on the optimal surgical approach
      between peritoneal drainage and laparotomy; the best course of action likely
      depends on the infant's comorbidities, hemodynamic status, size, disease
      involvement, and available resources. Patients who develop surgical NEC are at a
      significant risk for morbidity and mortality, with long-term complications
      including short bowel syndrome, growth failure, and neurodevelopmental
      impairment. Further research into strategies that optimize outcomes following
      surgery for NEC in the neonatal intensive care unit and long-term are paramount.

PMID- 30196018
TI  - T-type calcium channel enhancer SAK3 produces anti-depressant-like effects by
      promoting adult hippocampal neurogenesis in olfactory bulbectomized mice.
AB  - T-type calcium channels are involved in the pathophysiology of epilepsy, pain,
      and sleep. Recently, we developed a novel spiroimidazopyridine compound, SAK3
      (ethyl 8'-methyl-2',4-dioxo-2-(piperidin-1-yl)-2'H-spiro[cyclopentane-1,3'
      imidazo[1,2-a]pyridine]-2-ene-3-carboxylate), which enhances T-type calcium
      channel currents and improves memory deficits in olfactory bulbectomized (OBX)
      mice. Here, we demonstrated the anti-depressant effects of SAK3 in OBX mice.
      Chronic SAK3 administration (0.5 or 1.0 mg/kg, p.o.) improved depressive-like
      behaviors in OBX mice. The impaired adult neurogenesis in the hippocampal dentate
      gyrus (DG) that occurred 4 weeks after OBX administration was significantly
      restored by chronic SAK3 administration (0.5 or 1.0 mg/kg, p.o.). Additionally,
      SAK3 (0.5 mg/kg, p.o.) promoted the proliferation and survival of newborn cells
      in the naive DG. Moreover, SAK3 administration (0.5 mg/kg, p.o.) antagonized the
      reduction of calcium/calmodulin-dependent protein kinase II (CaMKII) and CaMKIV
      phosphorylation levels, thereby rescuing the decreased levels of cAMP response
      element-binding protein (CREB)/brain derived neurotrophic factor (BDNF) signaling
      in the OBX DG. The effects of SAK3 were completely blocked by the T-type calcium
      channel selective blocker NNC 55-0396 (12.5 mg/kg, i.p.). Altogether, these
      results suggest that SAK3 improves depressive-like behaviors by promoting adult
      neurogenesis via T-type calcium channel stimulation in the hippocampus.

PMID- 30196019
TI  - Glycine mitigates renal oxidative stress by suppressing Nox4 expression in rats
      with streptozotocin-induced diabetes.
AB  - Glycine exerts renoprotective effects, but the mechanism remains unclear. Glycine
      is increasingly recognized as a factor that attenuates oxidative stress, a key
      mechanism underlying diabetic nephropathy. In this study, we investigated the
      effects of glycine on diabetic renal injury and oxidative stress by adding 1%
      glycine in the drinking water of rats with streptozotocin-induced diabetes for 20
      weeks. Glycine levels decreased in the plasma and kidney homogenates of diabetic
      rats but were restored by oral glycine administration. In these diabetic rats,
      glycine attenuated renal damage, as evidenced by the decreased mesangial
      expansion, tubular interstitial fibrosis, and neutrophil gelatinase-associated
      lipocalin (NGAL) expression. Glycine also ameliorated the raise in urinary
      malondialdehyde (MDA) levels and partially restored renal glutathione levels in
      diabetic rats. Renal levels of the Nox4 mRNA and protein, a major source of renal
      oxidative stress, were suppressed by the treatment with glycine.
      Immunohistological analysis revealed that glycine had protective effects on the
      tubular area rather than the glomerular area. Our results strongly suggest that
      the protective effect of glycine on renal oxidative stress and structural damage
      may be linked to enhancement of GSH synthesis and suppression of renal Nox4
      expression in diabetic rats.

PMID- 30196020
TI  - Resveratrol-loaded nanoemulsion prevents cognitive decline after abdominal
      surgery in aged rats.
AB  - The maladaptive response of aged microglia to surgery and consequent
      neuroinflammation plays a key pathogenic role in postoperative cognitive
      dysfunction (POCD). Here, we assessed the preventive effect of resveratrol (RESV)
      for POCD in aged rats. The emulsified form of RESV (e-RESV) was selected to
      improve its oral and brain bioavailability. Animals were assigned to one of four
      groups: e-RESV (80 mg/kg) versus vehicle treatment by abdominal surgery versus
      isoflurane anesthesia alone (n = 8 in each group). The dose-dependent effects of
      e-RESV were also assessed in dose range of 0-60 mg/kg. Either vehicle or e-RESV
      was administered intragastrically 24 h before surgery. Seven days after
      procedure, cognitive function was evaluated using a novel object recognition
      test, followed by measurement of hippocampal pro-inflammatory cytokine levels.
      Our results showed that pre-treatment with e-RESV attenuated the surgery-induced
      cognitive impairment and related hippocampal neuroinflammation at 40 mg/kg or
      higher doses. Additionally, the ex-vivo experiments revealed that the preemptive
      e-RESV regimen reduced the hippocampal microglial immune reactivity to
      lipopolysaccharide. Furthermore, e-RESV induced neuroprotective benefits were
      inhibited by the concomitant administration of sirtinol, a specific SIRT1
      inhibitor. Our findings imply the preventive potential of e-RESV for POCD via the
      SIRT1 signaling pathway.

PMID- 30196021
TI  - Commentary - consensus research priorities for facial palsy: A delphi survey of
      patients, carers, clinicians and researchers.

PMID- 30196022
TI  - Diagnostic value of fluorine-18 deoxyglucose positron emission
      tomography/computed tomography in deep sternal wound infection.
AB  - OBJECTIVES: Deep sternal wound infection (DSWI) is a refractory complication
      after heart surgery, and debridement is the first-line treatment. The accurate
      identification of the extent of the infection is the key to successful
      debridement. The present study assessed the diagnostic accuracy of fluorine-18
      deoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT)
      for identifying the infected area of DSWI. METHODS: Between February 2015 and May
      2017, 73 consecutive patients with suspected DSWI received 18F-FDG PET/CT
      examinations before their operation. The PET/CT and extracted CT images were
      analyzed by nuclear medicine physicians and radiologists to determine whether the
      sternum, mediastinum, vascular prosthesis, and each costal cartilage were
      infected. All the patients received debridement and chest wall reconstruction
      within 1 week following the PET scan. The final diagnosis was on the basis of
      surgical, microbiological, and histopathological findings. RESULTS: Of the 73
      patients, 64, 54, 28, and 6 patients were diagnosed with sternal osteomyelitis,
      mediastinitis, costal chondritis, and vascular graft infection (VGI),
      respectively. The sensitivities of PET/CT for diagnosing sternal osteomyelitis,
      mediastinitis, and costal chondritis were 98.4%, 77.8%, and 100.0%, respectively,
      and the corresponding specificities were 94.7%, 82.1%, and 100.0%, respectively.
      PET/CT correctly diagnosed all six cases of VGI. There were 65 infected costal
      cartilages in the patients with costal chondritis. The sensitivity, specificity,
      and accuracy of PET/CT for locating infected costal cartilages were 81.5%, 99.8%,
      and 98.6%, respectively. CONCLUSIONS: PET/CT proved to be a useful tool for
      determining the depth of DSWI and for locating infected costal cartilage;
      therefore, this tool can help guide debridement.

PMID- 30196023
TI  - Re-Using the internal mammary artery as recipient artery in cervicofacial
      reconstruction by fibular flap.

PMID- 30196024
TI  - Letter responds to comment on published paper: "Using the internal mammary artery
      as recipient artery in cervicofacial reconstruction by fibular flap".

PMID- 30196025
TI  - Adjuvant radiotherapy as a risk factor for developing capsular contracture in
      women after breast implant surgery.

PMID- 30196026
TI  - Aspect of brow position changes after bilateral ptosis correction surgery.

PMID- 30196027
TI  - Characterizing cancer cachexia in the geriatric oncology population.
AB  - OBJECTIVES: Cancer cachexia, characterized by weight loss and sarcopenia, leads
      to a decline in physical function and is associated with poorer survival. Cancer
      cachexia remains poorly described in older adults with cancer. This study aims to
      characterize cancer cachexia in older adults by assessing its prevalence
      utilizing standard definitions and evaluating associations with components of the
      geriatric assessment (GA) and survival. MATERIALS AND METHODS: Patients with
      cancer older than 65 years of age who underwent a GA and had baseline CT imaging
      were eligible in this cross-sectional study. Cancer cachexia was defined by the
      international consensus definition reported in 2011. Sarcopenia was measured
      using cross-sectional imaging and utilizing sex-specific cut-offs. Associations
      between cachexia, sarcopenia, and weight loss with survival and GA domains were
      explored. RESULTS: Mean age of 100 subjects was 79.9 years (66-95) and 65% met
      criteria for cancer cachexia. Cachexia was associated with impairment in
      instrumental activities of daily living (IADL) (p = .017); no significant
      association was found between sarcopenia or weight loss and IADL impairment.
      Cachexia was significantly associated with poorer survival (median 1.0 vs 2.1
      years, p = .011). CONCLUSIONS: Cancer cachexia as defined by the international
      consensus definition is prevalent in older adults with cancer and is associated
      with functional impairment and decreased survival. Larger prospective studies are
      needed to further describe cancer cachexia in this population.

PMID- 30196028
TI  - Participation of adults with visual and severe or profound intellectual
      disabilities: Analysis of individual support plans.
AB  - BACKGROUND: The extent of participation of adults with visual and severe or
      profound intellectual disabilities (VSPID) is unclear. AIMS: To explore
      participation of adults with VSPID and the association between occurrence and
      importance of aspects of participation. METHODS: Individual support plans (ISPs)
      of 40 adults with VSPID were analyzed: selected text fragments were categorized
      according to 125 previously operationalized statements that had different levels
      of importance and were divided into seven participation clusters. RESULTS: The
      ISPs contained 2791 text fragments that related to a statement. All clusters were
      covered: the clusters 'Experience and discover' (91.7%), 'Involvement' (90%), and
      'Social relations' (87.5%) were well covered. 'Inclusion' (53.6%) and 'Leisure
      and recreation' (57.1%) were mentioned less often. Among the 36 high-importance
      statements, two related to 'Inclusion', 'Involvement' and 'Social Relations'
      each, three to 'Communication and being understood', and five to 'Self-management
      and autonomy' had at least 30 text fragments. CONCLUSIONS: The participation
      domains 'Experience and discover', 'Involvement', and 'Social relations' are well
      documented, suggesting that adults with VSPID participate in those areas.
      However, domains such as 'inclusion in society' and 'leisure in society' were not
      documented. This overview of participation offers residential facilities the
      opportunity to determine in which areas participation can be improved.

PMID- 30196029
TI  - A novel nanocarrier sirolimus-coated balloon for coronary interventions: 12-Month
      data from the Nanolute Registry.
AB  - BACKGROUND: The aim of the Nanolute registry was to observe the clinical
      performance of a novel sirolimus coated balloon (SCB) (Concept Medical Research
      Private Limited, India) for the treatment of coronary de-novo and restenotic
      lesions. METHODS: All patients treated with SCB between July 2012 and September
      2015 were enrolled at Indian centres and clinically followed for 1, 3, 6 and 12
      months post-procedure. Primary endpoints were procedural success and device
      oriented adverse cardiac events (DOCE) at 12 months. DOCE were defined as a
      composite of cardiac death, target lesion revascularization (TLR) and target
      vessel-myocardial infarction. RESULTS: A total of 394 SCB were used in 332
      patients to treat 356 lesions. In-stent restenosis and small coronary vessel
      disease occurred in 46% and 43% of the patients respectively. Mean balloon length
      and diameter (average +/- SD) were 21.83 +/- 6.70 mm and 2.69 +/- 0.45 mm
      respectively. All patients with 1 year follow-up were included. Overall DOCE rate
      was 4.2% (n = 14) which included death 0.3% (n = 1), TLR 3.6% (n = 12) and
      myocardial infarction 0.3% (n = 1). CONCLUSION: The Nanolute prospective
      registry, is the first clinical evidence of the safety and feasibility of this
      type of SCB, both in patients with in-stent restenosis or de novo lesions.

PMID- 30196030
TI  - Network Meta-analysis of percutaneous intervention-based revascularization
      strategies for ST-elevation myocardial infarction and concomitant multi-vessel
      disease.
AB  - BACKGROUND: In patients with ST elevation myocardial infarction (STEMI) and
      concomitant multi-vessel disease (MVD), primary percutaneous coronary
      intervention (PCI) of the culprit vessel is the preferred reperfusion strategy.
      However, optimum timing of revascularization for non-culprit artery is unclear.
      In this Bayesian network meta-analysis (NMA), we compared different PCI-based
      revascularization strategies in STEMI patients with MVD. METHODS: 11 randomized
      controlled trials (RCTs) were selected using MEDLINE, EMBASE and CENTRAL
      (Inception to September 2017). For all outcomes, median estimate of odds ratio
      from posterior distribution with corresponding 95% credible interval was
      calculated. The Surface under the Cumulative Ranking Curve (SUCRA) metric was
      used to estimate the relative ranking probability of each intervention.
      Sensitivity analysis was conducted by excluding the RCTs in which the staged
      intervention was performed after two weeks of the index procedure or post
      discharge. RESULTS: In this NMA of 3172 patients, CR-I (instant complete
      revascularization) was associated with 40% relative risk reduction in all-cause
      mortality compared with IRA (infarct related artery) [0.60 (0.31-0.89)]. CR-I was
      superior to CR-S (staged complete revascularization) [0.42 (0.22-0.70)] and IRA
      [0.50(0.29-0.72)] in reducing the risk of re- infarction. Both CR-I and CR-S
      significantly reduced the risk of repeat revascularization compared to IRA,
      whereas the risk of CIN (contrast induced nephropathy) and major bleeding was
      similar across all interventions. Sensitivity analysis showed, that CR-I was a
      better strategy compared with CR-S [0.34 (0.12-0.74)] and IRA (0.60 [0.36-0.97])
      in reducing all-cause mortality. CONCLUSIONS: In this NMA, CR-I was associated
      with reduction in all-cause mortality and re- infarction compared with IRA.

PMID- 30196032
TI  - More evidence for further minimisation of breast-cancer surgery.

PMID- 30196033
TI  - Fabrication of nanocomposite photocatalyst CuBi2O4/Bi3ClO4 for removal of acid
      brown 14 as water pollutant under visible light irradiation.
AB  - In the present study, CuBi2O4/Bi3ClO4 nanocomposites have been fabricated via an
      improved Pechini sol-gel process using the mixtures of various gelling agents and
      polybasic acids. This work shows that by controlling the reaction conditions such
      as kind of polybasic acids, gelling agents, pH and mole ratio of polybasic acid
      to total metals, the CuBi2O4/Bi3ClO4 nanocomposites with ultrafine sphere-like,
      irregular polyhedral-like, plate-like and cubic-like morphologies were prepared.
      The phase, elemental composition, morphology and optical characteristics of as
      synthesized CuBi2O4/Bi3ClO4 nanostructures were analyzed utilizing UV-Vis, FESEM,
      TEM, HRTEM, FT-IR, XRD, TOC and EDS techniques. Furthermore, the CuBi2O4/Bi3ClO4
      nanocomposites exhibited excellent TOC removal (75%) and photocatalytic activity
      (92%) to photodegradation of acid brown 14 azo dye as water pollutants under
      visible light irradiation. The excellent degradation activity of CuBi2O4/Bi3ClO4
      photocatalyst can be attributed to the strong visible light absorption, high
      charge separation efficiency, fine particle size distribution and proper band gap
      of the nanocomposite. In addition, the reliable photocatalytic mechanism was
      discussed on the basis of the radical trapping study, which revealed the h+ and
      O2- radicals were the prevailing active species in the photocatalytic process.

PMID- 30196034
TI  - Preparation of micro-electrolysis material from flotation waste of copper slag
      and its application for degradation of organic contaminants in water.
AB  - Flotation waste of copper slag (FWCS) was used as a raw material for the
      preparation of a micro-electrolysis material (MEM) through a carbothermal
      reduction process. The performance of MEM was evaluated for the degradation of
      organic contaminants in water. The effects of preparation conditions on the
      performance of MEM were investigated. Results showed that the MEM prepared under
      the conditions of calcination temperature of 1100  degrees C, calcination time of
      60 min, and coal dosage of 25% presented the best performance for degrading
      methyl orange (MO). The decolorization process was enhanced by increasing the MEM
      dosage, decreasing the initial pH of the solution, and raising the solution
      temperature. Moreover, the MEM presented good capability for the degradation of
      methylene blue, eosin Y, and acid fuchsin. X-ray diffraction (XRD) analysis
      showed that increasing the roasting temperature was beneficial to the formation
      of zero-valent iron (ZVI). Scanning electron microscopy (SEM) and energy
      dispersive spectroscopy (EDS) showed that micro-sized ZVI particles were formed
      in the MEM, and they contained a small amount of copper element. Meanwhile, the
      mechanism analysis showed that a redox reaction of the MEM and MO occurred, the
      azo bond of MO was destroyed, and sulfanilic acid was generated.

PMID- 30196031
TI  - Axillary dissection versus no axillary dissection in patients with breast cancer
      and sentinel-node micrometastases (IBCSG 23-01): 10-year follow-up of a
      randomised, controlled phase 3 trial.
AB  - BACKGROUND: We previously reported the 5-year results of the phase 3 IBCSG 23-01
      trial comparing disease-free survival in patients with breast cancer with one or
      more micrometastatic (<=2 mm) sentinel nodes randomly assigned to either axillary
      dissection or no axillary dissection. The results showed no difference in disease
      free survival between the groups and showed non-inferiority of no axillary
      dissection relative to axillary dissection. The current analysis presents the
      results of the study after a median follow-up of 9.7 years (IQR 7.8-12.7).
      METHODS: In this multicentre, randomised, controlled, open-label, non
      inferiority, phase 3 trial, participants were recruited from 27 hospitals and
      cancer centres in nine countries. Eligible women could be of any age with
      clinical, mammographic, ultrasonographic, or pathological diagnosis of breast
      cancer with largest lesion diameter of 5 cm or smaller, and one or more
      metastatic sentinel nodes, all of which were 2 mm or smaller and with no
      extracapsular extension. Patients were randomly assigned (1:1) before surgery
      (mastectomy or breast-conserving surgery) to no axillary dissection or axillary
      dissection using permuted blocks generated by a web-based congruence algorithm,
      with stratification by centre and menopausal status. The protocol-specified
      primary endpoint was disease-free survival, analysed in the intention-to-treat
      population (as randomly assigned). Safety was assessed in all randomly assigned
      patients who received their allocated treatment (as treated). We did a one-sided
      test for non-inferiority of no axillary dissection by comparing the observed
      hazard ratios (HRs) for disease-free survival with a margin of 1.25. This 10-year
      follow-up analysis was not prespecified in the trial's protocol and thus was not
      adjusted for multiple, sequential testing. This trial is registered with
      ClinicalTrials.gov, number NCT00072293. FINDINGS: Between April 1, 2001, and Feb
      8, 2010, 6681 patients were screened and 934 randomly assigned to no axillary
      dissection (n=469) or axillary dissection (n=465). Three patients were ineligible
      and were excluded from the trial after randomisation. Disease-free survival at 10
      years was 76.8% (95% CI 72.5-81.0) in the no axillary dissection group, compared
      with 74.9% (70.5-79.3) in the axillary dissection group (HR 0.85, 95% CI 0.65
      1.11; log-rank p=0.24; p=0.0024 for non-inferiority). Long-term surgical
      complications included lymphoedema of any grade in 16 (4%) of 453 patients in the
      no axillary dissection group and 60 (13%) of 447 in the axillary dissection
      group, sensory neuropathy of any grade in 57 (13%) in the no axillary dissection
      group versus 85 (19%) in the axillary dissection group, and motor neuropathy of
      any grade (14 [3%] in the no axillary dissection group vs 40 [9%] in the axillary
      dissection group). One serious adverse event (postoperative infection and
      inflamed axilla requiring hospital admission) was attributed to axillary
      dissection; the event resolved without sequelae. INTERPRETATION: The findings of
      the IBCSG 23-01 trial after a median follow-up of 9.7 years (IQR 7.8-12.7)
      corroborate those obtained at 5 years and are consistent with those of the 10
      year follow-up analysis of the Z0011 trial. Together, these findings support the
      current practice of not doing an axillary dissection when the tumour burden in
      the sentinel nodes is minimal or moderate in patients with early breast cancer.
      FUNDING: International Breast Cancer Study Group.

PMID- 30196035
TI  - Combined pollution of copper nanoparticles and atrazine in soil: Effects on
      dissipation of the pesticide and on microbiological community profiles.
AB  - Copper nanoparticles (NCu) have been proposed as an antimicrobial agent in
      agriculture. Therefore, NCu may interact with numerous pollutants including
      pesticides. Little is known about the combined effects of NCu and pesticides in
      soil. This study aimed at assessing the impact of NCu combined with the herbicide
      atrazine (ATZ) on soil. We focused on assessing the adsorption and dissipation of
      ATZ in the presence of NCu and the changes in microbial community profiles.
      First, ATZ adsorption isotherms (described using the Freundlich equation) were
      evaluated. After that, soil samples were spiked with NCu (40-60 nm) at 0.05 and
      0.15% w/w and ATZ (3 mg a.i kg-1) and incubated for 30 days. The results showed
      that ATZ adsorption is favored by the presence of NCu. On the other hand, NCu at
      0.15% w/w caused a significant decrease in ATZ dissipation, increasing its half
      life from 6 to 37 days. Microbial community profiles (bacteria, fungi and
      nitrifying bacteria) remained relatively stable throughout the evaluated period.
      Therefore, our findings suggest that NCu can increase the persistence of ATZ in
      soil, which may be mostly associated to physical-chemical interaction with soil
      particles more than a microbial impact.

PMID- 30196036
TI  - Corrigendum to "Engineered viral vectors for functional interrogation,
      deconvolution, and manipulation of neural circuits" [Curr. Opin. Neurobiol. 50
      (2018) 163-170].

PMID- 30196037
TI  - Reduced colonic smooth muscle cholinergic responsiveness is associated with
      impaired bowel motility after chronic experimental high-level spinal cord injury.
AB  - The mechanisms underlying bowel dysfunction after high-level spinal cord injury
      (SCI) are poorly understood. However, impaired supraspinal sympathetic and
      parasympathetic control is likely a major contributing factor. Disruption of the
      descending autonomic pathways traversing the spinal cord was achieved by a T3
      complete spinal cord transection, and colonic function was examined in vivo and
      ex vivo four weeks post-injury. Total gastrointestinal transit time (TGTT) was
      reduced and contractility of the proximal and distal colon was impaired due to
      reduced M3 receptor sensitivity. These data describe a clinically relevant model
      of bowel dysfunction after SCI.

PMID- 30196038
TI  - Breastfeeding knowledge and attitudes of baccalaureate nursing students in
      Taiwan: A cohort study.
AB  - BACKGROUND: Optimal nutrition during the first year of life is critical to
      infants' healthy growth and development. Hence, it is vital that undergraduate
      health professional curricula provide good quality learning environments to
      enable students to acquire the necessary knowledge and skills to support
      breastfeeding mothers. AIMS: To examine the change in knowledge and attitude in
      Taiwanese nursing students following theoretical and clinical learning
      experiences on breastfeeding. METHODS: This study used a pre-test/post-test
      survey design with two cohorts of nursing students (N=215). Knowledge and
      attitude were assessed before and after: (a) theoretical (didactic and skills
      laboratory) education in Cohort One, and (b) clinical placement in Cohort Two.
      FINDINGS: Students in both cohorts demonstrated significant improvements in
      knowledge and attitude post-theoretical education, and post-clinical placement.
      Prior to theoretical education in Cohort One, those with experience of close
      family members being breastfed were more than 14 times (adjusted odds ratio:
      14.09, 95% confidence interval: 1.73-114.64) to be in the high knowledge group.
      However, following theoretical or clinical education, there were no
      sociodemographic group differences in breastfeeding knowledge or attitude in
      Cohorts One or Two. CONCLUSION: Results revealed that the current breastfeeding
      education program in Taiwan, both theoretical and clinical components, increased
      nursing students' knowledge and improved positive attitudes towards
      breastfeeding, and any sociodemographic differences in knowledge and attitude
      about breastfeeding were ameliorated following theoretical and clinical placement
      experience focused on breastfeeding.

PMID- 30196039
TI  - Practitioner accreditation for the practice of water immersion during labour and
      birth: Results from a mixed methods study.
AB  - BACKGROUND: Water immersion for labour and birth is an option that is
      increasingly favoured by women. Australian water immersion policies and
      guidelines commonly specify that practitioners, such as midwives, must undertake
      further education and training to become accredited. METHOD: A three-phase mixed
      methods approach was used. Phase one used critical discourse analysis to
      determine who or what informs policies and guidelines related to water immersion
      for labour and/or birth. Phase two examined policy and guideline informants'
      experiences of the development of policies/guidelines, whilst phase three
      surveyed Australian midwives' views and experiences of water immersion and their
      use of and/or involvement in the development of policies and guidelines.
      FINDINGS: Practitioner accreditation for the facilitation of water immersion was
      a common finding across all phases of the study. An examination of policies and
      guidelines found that practitioners, namely midwives, were required to meet
      additional training requirements to facilitate water immersion. Participants of
      phases two and three identified and discussed accreditation as a significant
      challenge to the option of water immersion, particularly where there were
      inconsistencies across documents and in the interpretation of their content.
      CONCLUSION: The need for practitioners to be accredited to facilitate water
      immersion was identified as a major barrier to availability and therefore,
      women's ability to access the option. Given these findings, the need for
      accreditation should be challenged.

PMID- 30196040
TI  - Effects of Product Handling Parameters on Particle Levels in a Commercial Factor
      VIII Product: Impacts and Mitigation.
AB  - To reduce the risk of immunogenicity that may be caused by therapeutic protein
      products, it is important to properly characterize subvisible particles and to
      develop strategies to reduce the levels of particles delivered to patients. In
      the present study, by using state-of-the-art methods to quantify particle levels,
      we found that the factor VIII product, Kogenate FS, contained relatively high
      levels of protein particles and silicone oil droplets, the vast majority of which
      were submicron in size. In a test of effects of product mishandling, the Kogenate
      FS vial was shaken instead of swirled during reconstitution. Levels of silicone
      oil droplets and protein particles were increased. In contrast, these levels were
      greatly reduced by 2 mitigation strategies tested, using a nonsiliconized syringe
      for the diluent container or using submicron pore size syringe filters during
      simulated infusion. Thus, to avoid potential adverse effects due to mishandling
      induced increases in particle levels, it is important to educate end-users about
      proper product handling. Furthermore, effective particle mitigation and reduction
      strategies should be developed for factor VIII, and other therapeutic protein
      products. Such efforts could lead to clinically useful approaches to reduce the
      levels of particles delivered to patients and to an associated reduction in
      adverse immunogenicity.

PMID- 30196041
TI  - Pharmacokinetics and Pharmacodynamics of Escalating Doses of SHetA2 After Vaginal
      Administration to Mice.
AB  - SHetA2 is a novel compound with strong potential to treat cervical dysplasia, but
      its low aqueous solubility limits its oral bioavailability. A vaginal suppository
      achieved SHetA2 cervix concentrations that were severalfold above the predicted
      therapeutic levels. Thus, we aimed at determining the minimum dose that would
      achieve SHetA2 therapeutic levels while reducing cyclin D1 levels, the
      pharmacodynamic end point. The disposition of SHetA2 after vaginal administration
      of escalating SHetA2 doses and the corresponding reduction in cyclin D1 levels
      was compared to that after the conventional oral treatment. Vaginal
      administration of a 15-mg/kg dose achieved an area under the cervix concentration
      versus time curve (AUCcervix) that was ~120 times larger than that after a 60
      mg/kg administered orally. AUCcervix and Cmax-cervix did not increase
      proportionally with respect to the dose, with the 30-mg/kg dose resulting in
      higher AUCcervix and Cmax-cervix (1368.53 MUg.mL/h and 155.38 MUg/g,
      respectively) compared to the 15 mg/kg (334.98 MUg.mL/h and 121.78 MUg/g,
      respectively) or 60 mg/kg (1178.55 MUg.mL/h and 410.38 MUg/g, respectively).
      Likewise, the 30-mg/kg dose caused a larger reduction in cyclin D1 levels than
      the other doses. Thus, the 30-mg/kg dose was selected for future efficacy studies
      in a mouse model of cervical neoplasia.

PMID- 30196042
TI  - The effects of changes to the built environment on the mental health and well
      being of adults: Systematic review.
AB  - There is increasing interest in the influence of place on health, and the need to
      distinguish between environmental and individual level factors. For environmental
      level factors, current evidence tends to show associations through cross
      sectional and uncontrolled longitudinal analyses rather than through more robust
      study designs that can provide stronger causal evidence. We restricted this
      systematic review to randomised (or cluster) randomised controlled trials and
      controlled before-and-after studies of changes to the built environment. Date of
      search was December 2016. We identified 14 studies. No evidence was found of an
      effect on mental health from 'urban regeneration' and 'improving green
      infrastructure' studies. Beneficial effects on quality-of-life outcomes from
      'improving green infrastructure' were found in two studies. One 'improving green
      infrastructure' study reported an improvement in social isolation. Risk-of-bias
      assessment indicated robust data from only four studies. Overall, evidence for
      the impact of built environment interventions on mental health and quality-of
      life is weak. Future research requires more robust study designs and
      interdisciplinary research involving public health, planning and urban design
      experts.

PMID- 30196043
TI  - Residential mobility during pregnancy in Urban Gansu, China.
AB  - BACKGROUND: Studies on environmental exposures during pregnancy commonly use
      maternal residence at time of delivery, which may result in exposure
      misclassification and biased estimates of exposure and disease association.
      Studies on residential mobility during pregnancy are needed in various
      populations to aid studies of the environmental exposure and birth outcomes.
      However, there is still a lack of studies investigating residential mobility
      patterns in Asian populations. METHODS: We analyzed data from 10,542 pregnant
      women enrolled in a birth cohort study in Lanzhou, China (2010-2012), a major
      industrial city. Multivariate logistic regression was used to evaluate
      residential mobility patterns in relation to maternal complications and birth
      outcomes. RESULTS: Of the participants, 546 (5.2%) moved during pregnancy; among
      those who moved, 40.5%, 34.8%, and 24.7% moved during the first, second, and
      third trimester, respectively. Most movers (97.3%) moved once with a mean
      distance of 3.75 km (range: 1-109 km). More than half (66.1%) of the movers moved
      within 3 km, 13.9% moved 3-10 km, and 20.0% moved > 10 km. Pregnant women who
      were > 30 years or multiparous, or who had maternal complications were less
      likely to have moved during pregnancy. In addition, movers were less likely to
      deliver infants with birth defects, preterm births, and low birth weight.
      CONCLUSIONS: Residential mobility was significantly associated with several
      maternal characteristics and complications during pregnancy. The study also
      showed a lower likelihood of adverse birth outcomes among movers than non-movers,
      suggesting that moving might be related to reduce exposure to environmental
      hazards. These results confirm the hypothesis that residential mobility may be
      important with respect to exposure misclassification and that this
      misclassification may vary by subpopulations.

PMID- 30196044
TI  - Assessing Treatment Tolerability for Rheumatoid Arthritis. Validation and
      Practical Applications of the 'TOL-AR-18 Questionnaire'.
AB  - INTRODUCTION: Given the lack of standardized tools to assess tolerability from
      patient's perspective, we carried out the validation of a questionnaire to asses
      treatment tolerability for rheumatoid arthritis (RA): TOL-AR-18. METHODS: The TOL
      AR-18 was validated in the cross-sectional observational study in adult patients
      with RA. Socio-demographic and clinical variables were collected. Patients
      completed the TOL-AR-18 and ARTS questionnaires and a question about their
      general health status. RESULTS: Data of 66 patients with a mean age (standard
      deviation; SD) of 56.71 (10.50) years were analyzed; 66.7% were women. Mean (SD)
      time to disease progression was 10.76 (8.23) years, and time from first treatment
      initiation was 9.24 (7.70) years. Patients did not report other adverse events
      rather than those included in the TOL-AR-18. The questionnaire was feasible with
      high internal consistency (Cronbach's alpha >0.90). Discriminant validity was
      moderate, with significant differences between patients in remission and all
      other, and between patients who did not report adverse events and the rest
      (P<.05). Convergent validity was moderate-low when correlated with the ARTS
      questionnaire. CONCLUSION: The TOL-AR-18 is valid for use in a clinical setting
      and useful as an additional tool for all professionals to manage and assess
      tolerability in RA.

PMID- 30196045
TI  - Prevalence of Clinical and Radiological Osteoarthritis in Knee, Hip, and Hand in
      an Urban Adult Population of Mexico City.
AB  - INTRODUCTION: Osteoarthritis (OA) is the most prevalent articular disease
      worldwide, and its prevalence is highly variable depending on the classification
      criteria, population studied, and/or affected joints considered. Reporting
      epidemiologic data about clinical and radiological OA prevalence in Mexico has
      not been done before. PATIENTS AND METHODS: A descriptive cross-sectional study
      was carried out with participants of Mexico City, and included both men and women
      above 40 years of age. All participants were evaluated with radiological and
      clinical criteria for OA. RESULTS: Two hundred and four individuals participated
      in the study: 80 men (39.2%) and 124 women (60.8%). The average age was 57.4+/
      10.9 years. Using clinical criteria alone, 36 participants were found to have
      hand OA (17.6%; 95% CI, 13-23.4), 37 with hip OA (18.1%; 95% CI 13.4-24), and 40
      with knee OA (19.6%; 95% CI 14.7-25.6). When radiological criteria were used, 51
      individuals were reported as having hand OA (25%; 95% CI 19.5-31), 54 with hip OA
      (26.5%; 95% CI 20.8-32.9), and 52 with knee OA (25.5%; 95% CI 20-31.8). When
      clinical criteria were used and then corroborated with radiological criteria, the
      prevalence was 28 individuals with hand OA (13.7%; 95% CI 9.6-19), 31 with hip OA
      (15.1%; 95% CI 10.9-20.7), and 36 with knee OA 36 (17.6%; 95% CI 12.2-26.2).
      DISCUSSION: The prevalences found in this study are greater than those found in
      other studies in Mexico that only report clinical criteria.

PMID- 30196046
TI  - Graphene nanocomposites modified electrochemical aptamer sensor for rapid and
      highly sensitive detection of prostate specific antigen.
AB  - Prostate specific antigen (PSA) is a widely used marker for the diagnosis of
      prostate cancer, and the increasing attention has been attracted on the
      development of rapid assay using biosensing technology. However, it remains
      challenging for the sensitive and selective detection of PSA in clinical samples.
      Here, we report a label-free microfluidic paper-based analytical device for
      highly sensitive electrochemical detection of PSA. The paper device was
      fabricated with wax printing to generate hydrophobic and hydrophilic layers for
      the construction of microfluidic channel, followed by screen-printing of three
      electrodes including working, counter and reference electrode. Gold nanoparticles
      (AuNPs)/reduced graphene oxide (rGO)/thionine (THI) nano composites were
      synthesized and characterized, which were coated onto working electrodes for the
      immobilization of DNA aptamer probe. THI servers as the electrochemical mediator
      to transduce the biological recognition between DNA aptamer and PSA, and the
      excellent conductivity of AuNPs and rGO also play a significant role of electron
      transfer, leading to a sensitive detection for PSA, able to detect PSA as low as
      10 pg mL-1, with a linear range from 0.05 to 200 ng mL-1. We demonstrated that
      our electrochemical sensor for the detection of clinical serum samples,
      indicating that our sensor would provide a new platform for low cost, sensitive
      and point-of-care diagnosis of prostate cancer.

PMID- 30196047
TI  - An electrochemical strategy with tetrahedron rolling circle amplification for
      ultrasensitive detection of DNA methylation.
AB  - Sensitive and specific detection of DNA methylation in genomic DNA is imperative
      for rapid epigenetic evaluations. Here, a novel sensitive electrochemical
      strategy was developed for ultrasensitive detection of DNA methylation in genomic
      DNA via padlock probe primer generating rolling circle amplification (RCA).
      Typically, after bisulfite treatment of methylated DNA, the methylation-specific
      linear padlock is only circularized in the presence of methylated DNA and
      subsequently serves as a template containing a DNA tetrahedron for RCA. The DNA
      tetrahedron is utilized as a nanocarrier that can be immobilized on a gold
      electrode to generate RCA product to load hemin, an iron-containing porphyrin
      with chlorine, forming the G-quadruplex as a horseradish peroxidase like DNAzyme,
      which reduces methylene blue (MB) in the presence of H2O2 to yield a distinct
      current signal. Using the developed DNAzyme with the RCA signal amplification
      strategy, the DNA biosensor can achieve a detection limit as low as 0.1 fM for
      the ultrasensitive electrochemical detection of methylated DNA sequence with a
      detection range from 10-15 M to 10-9 M. At the same time, the satisfactory
      specificity, reproducibility, stability and recovery performances indicated its
      satisfied potentials for clinical diagnosis. Most importantly, this method can be
      further applied to analyse other genomic DNA also.

PMID- 30196048
TI  - Molecular architecture for DNA wiring.
AB  - Detection of the hybridisation events is of great importance in many different
      biotechnology applications such as diagnosis, computing, molecular
      bioelectronics, and among others. However, one important drawback is the low
      current of some redox reporters that limits their application. This paper
      demonstrates the powerful features of molecular wires, in particular the case of
      S-[4-[2-[4-(2-Phenylethynyl)phenyl]ethynyl]phenyl] thiol molecule and the key
      role that play the nanometric design of the capture probe linkers to achieve an
      efficient couple of the DNA complementary ferrocene label with the molecular wire
      for an effective electron transfer in co-immobilised self-assembled monolayers
      (SAMs) for DNA hybridisation detection. In this article, the length of the linker
      capture probe was studied for electron transfer enhancement from the ferrocene
      motifs of immobilised molecules towards the electrode surface to obtain higher
      kinetics in the presence of thiolated molecular wires. The use of the right
      couple of capture probe linker and molecular wire has found to be beneficial as
      it helps to amplify eightfold the signal obtained.

PMID- 30196049
TI  - Trypsin enhances aptamer screening: A novel method for targeting proteins.
AB  - A novel screening method for protein aptamer selection was developed in this
      study. Aptamers with high affinity and specificity to the surface recombinant
      antigen of Helicobacter pylori (HP-Ag) and to tumor markers carcinoembryonic
      antigen (CEA), cancer antigen 125 (CA125) and cancer antigen 19-9(CA19-9) were
      screened using trypsin enhanced screening method. Briefly, the target proteins
      above were immobilized onto 96-well polystyrene plates and incubated with a
      single-stranded DNA (ssDNA) library for aptamer selection. Then, trypsin was
      introduced to digest the proteins and obtain ssDNA that bound to the target
      proteins with high specificity. The concentration of ssDNA that shed from protein
      ssDNA complexes was detected. After sequencing, the enrichment of target-specific
      aptamers was monitored and the affinity of each aptamer was analyzed. Urea, which
      has been reported in other article, was used to compare with trypsin. The results
      revealed that trypsin was more effective than urea for protein aptamer selection.
      The protocol used in this study provided a novel method for generating aptamers.

PMID- 30196050
TI  - Neuromodulation targets pathological not physiological beta bursts during gait in
      Parkinson's disease.
AB  - Freezing of gait (FOG) is a devastating axial motor symptom in Parkinson's
      disease (PD) leading to falls, institutionalization, and even death. The response
      of FOG to dopaminergic medication and deep brain stimulation (DBS) is complex,
      variable, and yet to be optimized. Fundamental gaps in the knowledge of the
      underlying neurobiomechanical mechanisms of FOG render this symptom one of the
      unsolved challenges in the treatment of PD. Subcortical neural mechanisms of gait
      impairment and FOG in PD are largely unknown due to the challenge of accessing
      deep brain circuitry and measuring neural signals in real time in freely-moving
      subjects. Additionally, there is a lack of gait tasks that reliably elicit FOG.
      Since FOG is episodic, we hypothesized that dynamic features of subthalamic (STN)
      beta oscillations, or beta bursts, may contribute to the Freezer phenotype in PD
      during gait tasks that elicit FOG. We also investigated whether STN DBS at 60 Hz
      or 140 Hz affected beta burst dynamics and gait impairment differently in
      Freezers and Non-Freezers. Synchronized STN local field potentials, from an
      implanted, sensing neurostimulator (Activa(r) PC + S, Medtronic, Inc.), and gait
      kinematics were recorded in 12 PD subjects, off-medication during forward walking
      and stepping-in-place tasks under the following randomly presented conditions:
      NO, 60 Hz, and 140 Hz DBS. Prolonged movement band beta burst durations
      differentiated Freezers from Non-Freezers, were a pathological neural feature of
      FOG and were shortened during DBS which improved gait. Normal gait parameters,
      accompanied by shorter bursts in Non-Freezers, were unchanged during DBS. The
      difference between the mean burst duration between hemispheres (STNs) of all
      individuals strongly correlated with the difference in stride time between their
      legs but there was no correlation between mean burst duration of each STN and
      stride time of the contralateral leg, suggesting an interaction between
      hemispheres influences gait. These results suggest that prolonged STN beta burst
      durations measured during gait is an important biomarker for FOG and that STN DBS
      modulated long not short burst durations, thereby acting to restore physiological
      sensorimotor information processing, while improving gait.

PMID- 30196051
TI  - Decline in Sirtuin-1 expression and activity plays a critical role in blood-brain
      barrier permeability in aging.
AB  - Accumulating evidence suggest that cerebral microvascular disease increases with
      advancing age and is associated with lacunar stroke, leukoaraiosis, vascular
      dementia and Alzheimer disease. Increased blood brain barrier (BBB)
      permeability/leakage takes "center stage" in ongoing age-related vascular/brain
      parenchymal injury. Although significant effort has been made in defining the
      gene mutations and risk factors involved in microvascular alterations in vascular
      dementia and Alzheimer disease, the intra- and intercellular pathogenic
      mechanisms responsible for vascular hyperpermeability are still largely unknown.
      The present study aimed to reveal the ongoing senescence process in brain
      endothelial cells and its effect on BBB integrity in healthy/non-disease
      conditions. An analysis of BBB integrity during the life span of C56Bl6 mice
      (young, 2-6 months; middle-aged, 6-12, months; old, 16-22 months) showed
      increased BBB permeability for different molecular sized tracers (sodium
      fluorescein, inulin and 20 kDa dextran) in aged mice which was accompanied by
      modifications in tight junction (TJ) complex organization, manifested as altered
      TJ protein expression (particularly claudin-5). A gene screening analysis of
      aging associated markers in brain microvessels isolated from "aged" mice (C56Bl6,
      18-20 months) and human brain samples showed a significant decline in sirtuin-1
      expression (Sirt1; ~2.8-fold) confirmed at mRNA and protein levels and by
      activation assay. Experiments in Sirt1 transgenic mice and brain endothelial cell
      specific Sirt1 knockout mice indicated that Sirt1 affects BBB integrity, with
      loss increasing permeability. Similarly, in vitro, overexpressing Sirt1 or
      increasing Sirt1 activity with an agonist (Sirt1720) protected against senescence
      induced brain endothelial barrier hyperpermeability, stabilized claudin-5/ZO-1
      interactions and rescued claudin-5 expression. These findings reveal a novel role
      of Sirt1 in modulating aging-associated BBB persistent leakage.

PMID- 30196052
TI  - Peripheral Quantitative Computed Tomography: Review of Evidence and
      Recommendations for Image Acquisition, Analysis, and Reporting, Among Individuals
      With Neurological Impairment.
AB  - In 2015, the International Society for Clinical Densitometry (ISCD) position
      statement regarding peripheral quantitative computed tomography (pQCT) did not
      recommend routine use of pQCT, in clinical settings until consistency in image
      acquisition and analysis protocols are reached, normative studies conducted, and
      treatment thresholds identified. To date, the lack of consensus-derived
      recommendations regarding pQCT implementation remains a barrier to implementation
      of pQCT technology. Thus, based on description of available evidence and
      literature synthesis, this review recommends the most appropriate pQCT
      acquisition and analysis protocols for clinical care and research purposes, and
      recommends specific measures for diagnosis of osteoporosis, assigning fracture
      risk, and monitoring osteoporosis treatment effectiveness, among patients with
      neurological impairment. A systematic literature search of MEDLINE, EMBASE(c),
      CINAHL, and PubMed for available pQCT studies assessing bone health was carried
      out from inception to August 8th, 2017. The search was limited to individuals
      with neurological impairment (spinal cord injury, stroke, and multiple sclerosis)
      as these groups have rapid and severe regional declines in bone mass. Of 923
      references, we identified 69 that met review inclusion criteria. The majority of
      studies (n = 60) used the Stratec XCT 2000/3000 pQCT scanners as reflected in our
      evaluation of acquisition and analysis protocols. Overall congruence with the
      ISCD Official Positions was poor. Only 11% (n = 6) studies met quality reporting
      criteria for image acquisition and 32% (n = 19) reported their data analysis in a
      format suitable for reproduction. Therefore, based on current literature
      synthesis, ISCD position statement standards and the authors' expertise, we
      propose acquisition and analysis protocols at the radius, tibia, and femur sites
      using Stratec XCT 2000/3000 pQCT scanners among patients with neurological
      impairment for clinical and research purposes in order to drive practice change,
      develop normative datasets and complete future meta-analysis to inform fracture
      risk and treatment efficacy evaluation.

PMID- 30196053
TI  - Normative Data for Lean Mass and Fat Mass in Healthy Predominantly Breast-Fed
      Term Infants From 1 Month to 1 Year of Age.
AB  - BACKGROUND: A leaner body phenotype in infancy plays an important role in the
      early life prevention of obesity. However, there is a dearth of reference data
      for body composition in infancy. This study aimed to create a normative reference
      dataset for lean (LM) and fat (FM) mass and accretion rates in healthy infants.
      METHODS: Healthy term-born infants (35 boys; 35 girls) were studied at <= 1, 3,
      6, 9, and 12 mo of age for growth and compared to World Health Organization
      standards. LM (g) and FM (g) were measured using DXA (APEX version 13.3:3,
      Hologic 4500A) in infant whole-body mode. Sex specific reference curves were
      generated using the LMS method (LMSchartmaker, Medical Research Council, UK).
      RESULTS: Infants were predominantly white (82.9%), breastfed (98.4% >= 3 mo), and
      grew in length and weight within World Health Organization Z-score ranges for
      normal growth across infancy. LM accretion was 327.4 +/- 12.5 g/mo representing
      95% increment in LM. Boys had more LM compared to girls at 12 mo (7807.4 +/-
      1114.0 vs 6817.4 +/- 1016.1 g; p = 0.008). FM accretion was 114.3 +/- 12.0 g/mo
      representing 114% increment in FM with no difference between the sexes.
      CONCLUSIONS: This data, which is based on a healthy sample of infants,
      characterizes LM and FM accretion during the first year of life and will aid in
      the interpretation of body composition.

PMID- 30196054
TI  - Antipsychotic treatments: who is really failing here? - Authors' reply.

PMID- 30196055
TI  - Antipsychotic treatments: who is really failing here?

PMID- 30196056
TI  - Mebendazole potentiates radiation therapy in triple-negative breast cancer.
AB  - PURPOSE: The lack of a molecular target in triple negative breast cancer (TNBC)
      makes it one of the most challenging breast cancers to treat. Radiation therapy
      (RT) is an important treatment modality for managing breast cancer, however we
      previously showed that RT can also reprogram a fraction of the surviving BC cells
      into BC initiating cells (BCICs), that are thought to contribute to disease
      recurrence. In this study we characterize mebendazole as a drug with potential
      for preventing radiation-induced reprogramming from occurring and improve the
      effect of RT in TNBC patients. METHODS AND MATERIALS: A high-throughput screen
      was used to identify drugs that prevented radiation-induced conversion of TNBC
      cells into cells with a cancer- initiating phenotype and exhibited significant
      toxicity towards TNBC cells. Mebendazole (MBZ) was one of the drug hits that
      fulfilled these criteria. In additional studies we used BCIC markers and
      mammosphere forming assays to investigate the effect of MBZ on the BCIC
      population. Staining with propidium iodide, annexin-V and g-H2AX were used to
      determine the effect of MBZ on cell cycle, apoptosis and double-strand breaks.
      Finally, the potential for MBZ to enhance the effect of radiation therapy in TNBC
      was evaluated in vitro and in vivo. RESULTS: MBZ efficiently depletes the breast
      cancer initiating cell pool, as well as prevents the IR-induced conversion of BC
      cells into therapy resistant BCICs. In addition, MBZ arrests cells in the G2/M
      phase of the cell cycle arrest and causes double-strand breaks and apoptosis.
      Mebendazole sensitizes TNBC cells to ionizing radiation in vitro and in vivo
      resulting in improved tumor control in a human xenograft model of TNBC.
      CONCLUSIONS: The data presented in this study support the repurposing of
      mebendazole as a combination treatment with radiation therapy in TNBC patients.

PMID- 30196057
TI  - A genome editing vector that enables easy selection and identification of
      knockout cells.
AB  - The CRISPR/Cas9 system is a powerful genome editing tool for disrupting the
      expression of specific genes in a variety of cells. However, the genome editing
      procedure using currently available vectors is laborious, and there is room for
      improvement to obtain knockout cells more efficiently. Therefore, we constructed
      a novel vector for high efficiency genome editing, named pGedit, which contains
      EGFP-Bsr as a selection marker, expression units of Cas9, and sgRNA without a
      terminator sequence of the U6 promoter. EGFP-Bsr is a fusion protein of EGFP and
      blasticidin S deaminase, and enables rapid selection and monitoring of
      transformants, as well as confirmation that the vector has not been integrated
      into the genome. By using pGedit, we targeted human ACTB, ACTG1 and mouse Nes
      genes coding for beta-actin, gamma-actin and nestin, respectively. Knockout cell
      lines of each gene were easily and efficiently obtained in all three cases. In
      this report, we show that our novel vector, pGedit, significantly facilitates
      genome editing.

PMID- 30196058
TI  - Nanoencapsulation techniques for compounds and products with antioxidant and
      antimicrobial activity - A critical view.
AB  - Oxidative decay and microbial spoilage are issues of concern, as they constitute
      threats to human health. Natural antioxidants and antimicrobials hamper the
      negative impact of synthetic compounds and they need appropriate delivery
      systems. Different nanostructures can be developed: association colloids-based
      nanostructures, nanoemulsions, nanoliposomes, nanolaminates, nanofibers, carbon
      nanotubes, nanocomposites. The main nanoencapsulation techniques applied to
      antioxidants and antimicrobials are described: association colloid-based
      nanoincorporation, lipid-based nanoencapsulation techniques, encapsulation
      techniques based on biologically-derived polymeric nanocarriers, encapsulation
      techniques based on non-biological polymeric nanocarriers, cyclodextrin
      incorporation, electrospraying and electrospinning, carbon nanotubes and
      nanocomposite encapsulation. Several nanoencapsulation methods can be followed by
      freeze-drying or spray-drying. Protection of bioactive compounds and controlled
      release are achieved, but the impact of the nanomaterials on human health and on
      the environment should be considered. The influence of the nanoencapsulation
      techniques on the antioxidant/antimicrobial activity is discussed. The choice of
      the appropriate encapsulation method is vital. Bioactivity increase, preservation
      or decrease, depend on the interactions established between the functional groups
      of encapsulated compound and the encapsulating nanomaterial.

PMID- 30196059
TI  - Boronic ester-linked macrocyclic lipopeptides as serine protease inhibitors
      targeting Escherichia coli type I signal peptidase.
AB  - Type I signal peptidase, with its vital role in bacterial viability, is a
      promising but underexploited antibacterial drug target. In the light of steadily
      increasing rates of antimicrobial resistance, we have developed novel macrocyclic
      lipopeptides, linking P2 and P1' by a boronic ester warhead, capable of
      inhibiting Escherichia coli type I signal peptidase (EcLepB) and exhibiting good
      antibacterial activity. Structural modifications of the macrocyclic ring, the
      peptide sequence and the lipophilic tail led us to 14 novel macrocyclic boronic
      esters. It could be shown that macrocyclization is well tolerated in terms of
      EcLepB inhibition and antibacterial activity. Among the synthesized macrocycles,
      potent enzyme inhibitors in the low nanomolar range (e.g. compound 42f, EcLepB
      IC50 = 29 nM) were identified also showing good antimicrobial activity (e.g.
      compound 42b, E. coli WT MIC = 16 MUg/mL). The unique macrocyclic boronic esters
      described here were based on previously published linear lipopeptidic EcLepB
      inhibitors in an attempt to address cytotoxicity and hemolysis. We show herein
      that structural changes to the macrocyclic ring influence both the cytotoxicity
      and hemolytic activity suggesting that the P2 to P1' linker provide means for
      optimizing off-target effects. However, for the present set of compounds we were
      not able to separate the antibacterial activity and cytotoxic effect.

PMID- 30196060
TI  - Structure-based drug design: Synthesis and biological evaluation of quinazolin-4
      amine derivatives as selective Aurora A kinase inhibitors.
AB  - Aurora kinases play critical roles in the regulation of the cell cycle and
      mitotic spindle assembly. Aurora A kinase, a member of the Aurora protein family,
      is frequently highly expressed in tumors, and selective Aurora A inhibition
      serves as a significant component of anticancer therapy. However, designing
      highly selective Aurora A inhibitors is difficult because Aurora A and B share
      high homology and differ only by three residues in their ATP-binding pockets.
      Through structure-based drug design, we designed and synthesized a series of
      novel quinazolin-4-amine derivatives. These derivatives act as selective Aurora A
      kinase inhibitors by exploiting the structural differences between Aurora A and
      B. The selectivities of most compounds were improved (the best up to >757-fold)
      when comparing with the lead compound (3-fold). In vitro biochemical and cellular
      assays revealed that compound 6 potently inhibited Aurora A kinase and most human
      tumor cells. Furthermore, compound 6 effectively suppressed carcinoma, such as
      triple-negative breast cancers (TNBC) in an animal model. Therefore, compound 6
      might serve as a promising anticancer drug. Moreover, through molecular dynamic
      (MD) analysis, we have identified that a salt bridge formed in Aurora B is key
      contributor for the isoform selectivity of the inhibitor. This salt bridge has
      not been previously detected in the reported crystal structure of Aurora B. These
      results might provide a crucial basis for the further development of highly
      potent inhibitors with high selectivity for Aurora A.

PMID- 30196061
TI  - Structure-activity and structure-property relationships of novel Nrf2 activators
      with a 1,2,4-oxadiazole core and their therapeutic effects on acetaminophen
      (APAP)-induced acute liver injury.
AB  - The antioxidant function induced by Nrf2 protects the liver from damage. We found
      a novel Nrf2 activator named compound 25 via structural modification of compound
      1 we previously reported. In vitro, compound 25 induced Nrf2 transport into the
      nucleus and protected hepatocyte L02 cells from APAP-induced cytotoxicity via
      activating the Nrf2-ARE signaling pathway. In vivo, 25 exhibited therapeutic
      effects in a mouse model of acute liver injury induced by acetaminophen (APAP) by
      up-regulating Nrf2-dependent antioxidases and down-regulating liver injury
      markers in serum. Together, these results indicated that 25 is a potent Nrf2/ARE
      activator both in vitro and in vivo. The drug-like properties of compound 25
      further revealed its potential for development as a therapeutic drug against
      acute liver injury.

PMID- 30196062
TI  - Design, synthesis, and evaluation of chalcone analogues incorporate alpha,beta
      Unsaturated ketone functionality as anti-lung cancer agents via evoking ROS to
      induce pyroptosis.
AB  - Chalcone, a natural structure, demonstrates many pharmacological activities
      including anticancer, and one promising mechanism is to modulate the generation
      of ROS. It has been known that pyroptosis is associated with anticancer effects,
      whereas there is fewer researches about ROS-mediated pyroptosis triggered by
      chemotherapy drugs. Moreover, incorporation of a alpha,beta-unsaturated ketone
      unit into chalcone may be an effective strategy for development of chemotherapy
      drugs. Hence, a number of chalcone analogues bearing a alpha,beta-unsaturated
      ketone were synthesized from chalcone analogues 1 with modest anticancer
      activities as the lead compound. Structure-activity relationship (SAR) studies
      confirmed the function of alpha,beta-unsaturated ketone to improve anticancer
      activity. Notably, compound 8, bearing a alpha,beta-unsaturated ketone, is the
      most potent inhibitor of cancer, with IC50 values on NCI-H460, A549 and H1975
      cells of 2.3 +/- 0.3, 3.2 +/- 0.0 and 5.7 +/- 1.4 MUM, respectively. Besides, 8
      showed antiproliferative ability against NCI-H460 cells in a time- and
      concentration-dependent manner through modulating ROS to induce caspase-3
      mediated pyroptosis, and displayed a better safety profile in vivo. Overall,
      these results demonstrated that compound 8 is a candidate agent and a potential
      lead compound for development of chemotherapy drugs, and can be used as a probe
      to further examine the mechanism of ROS-dependent pyroptosis.

PMID- 30196063
TI  - Theoretical modeling of pre and postnatal growth.
AB  - A simultaneous analysis of the pre and postnatal growth data obtained for five
      exemplary animals (zebra, rat, guinea pig, chicken, tilapia) is performed. To
      this aim, the generalized von Bertalanffy (VB) model is employed in which one of
      the fitted parameters is related to the gestation or incubation period of the
      system under consideration. The results obtained reveal a descriptive power of
      the VB model in both the pre and postnatal stages for a wide range of the data
      analyzed using several goodness-of-fit metrics and biologically meaningful
      parameters fitted. It has been proved that generalized VB function with one
      parameter constrained to the experimental value of the gestation (incubation)
      period and other parameters fitted only to the postnatal data predicts with high
      accuracy the growth of animals in the developmental prenatal stages. Hence, the
      VB model features not only descriptive but also retro-predictive power to
      reproduce the prenatal growth patterns of the animals considered. Three main
      sources of the problems with the fit stability reported for the VB function are
      identified: nonlinear nature of the scaling n-exponent, its strong correlation
      with remaining parameters defining the model and n-value placed in the vicinity
      of the discontinuity point n = 1 or outside the standard range 0 <= n < 1 usually
      applied in the data analysis.

PMID- 30196064
TI  - Parasitism effects on coexistence and stability within simple trophic modules.
AB  - Parasites are important components of food webs. Although their direct effects on
      hosts are well-studied, indirect impacts on trophic networks, thus on non-host
      species, remain unclear. In this study, we investigate the consequences of
      parasitism on coexistence and stability within a simple trophic module: one
      predator consuming two prey species in competition. We test how such effects
      depend on the infected species (prey or predator). We account for two effects of
      parasitism: the virulence effect (parasites affect the infected species intrinsic
      growth rate through direct effects on fecundity or mortality) and the interaction
      effect (increased vulnerability of infected prey or increased food intake of
      infected predators). Results show that coexistence is favored when effects have
      intermediate intensity. We link this result to modifications of direct and
      apparent competitions among prey species. Given a prey infection, accounting for
      susceptible-infected population structure highlights that coexistence may also be
      reduced due to predator-parasite competition. Parasites affect stability by
      modulating energy transfer from prey to predator. Predator infection therefore
      has a stabilizing effect due to increased energy fluxes and/or predator
      mortality. Our results suggest that parasites potentially increase species
      coexistence. Precise predictions however require an assessment of various
      parasite effects. We discuss the implications of our results for the functioning
      of trophic networks.

PMID- 30196065
TI  - Cellular, transcriptomic and methylome effects of individual and combined
      exposure to BPA, BPF, BPS on mouse spermatocyte GC-2 cell line.
AB  - Environmental factors, particularly xenoestrogens adversely affect reproductive
      health and their main mechanism is based on steroid-signaling pathway
      alterations. The presence of bisphenol A (BPA) in the environment has been
      confirmed and it is about to be replaced by analogues such as bisphenol F (BPF)
      and bisphenol S (BPS). Whether the BPF and BPS exert similar adverse effects to
      BPA has become the subject of intense scientific scrutiny. The aim of the present
      study was to evaluate and compare the cellular, transcriptomic and methylome
      effects of exposure to BPA, BPF, BPS individually and in combination on GC-2
      spermatocyte cell line. The results show that all studied compounds affect cell
      viability, induce apoptosis and cause cellular damage. BPA, BPF and BPS also
      influence GC-2 cell steroid receptor and steroidogenesis related genes
      expressions. In addition to specific molecular mechanisms, all studied compounds
      also increase global DNA methylation. Exposure to a combination of all the
      studied compounds caused comparable effects on cell culture to each of them
      examined separately. These data suggest that exposure to BPA and its main
      substitutes- BPF and BPS induced multitude of effects and hence, BPF and BPS are
      not safe alternative to BPA in terms of male reproductive health.

PMID- 30196066
TI  - Triptolide enhances chemotherapeutic efficacy of antitumor drugs in non-small
      cell lung cancer cells by inhibiting Nrf2-ARE activity.
AB  - Non-small cell lung cancer (NSCLC) has a high mortality rate worldwide. Various
      treatments strategies have been used against NSCLC including individualized
      chemotherapies, but innate or acquired cancer cell drug resistance remains a
      major obstacle. Recent studies revealed that the Kelch-like ECH associated
      protein 1/Nuclear factor erythroid 2-related factor 2 (Keap1/Nrf2) pathway is
      intimately involved in cancer progression and chemoresistance. Thus, antagonizing
      Nrf2 would seem to be a viable strategy in cancer therapy. In the present study a
      traditional Chinese medicine, triptolide, was identified that markedly inhibited
      expression and transcriptional activity of Nrf2 in various cancer cells,
      including NSCLC and liver cancer cells. Consequently, triptolide made cancer
      cells more chemosensitivity toward antitumor drugs both in vitro and in a
      xenograft tumor model system using lung carcinoma cells. These results suggest
      that triptolide blocks chemoresistance in cancer cells by targeting the Nrf2
      pathway. Triptolide should be further investigated in clinical cancer trials.

PMID- 30196067
TI  - Understanding Modifiable Risk Factors for the Development of Myopia.

PMID- 30196068
TI  - Comparative Efficacy of Laparoscopic Versus Robotic Adrenalectomy for Adrenal
      Malignancy.
AB  - OBJECTIVE: To evaluate whether the technical advantages of robotic-assisted
      surgery over standard laparoscopy, which are well established for complex renal
      surgery, lead to variable surgical outcomes between laparoscopic adrenalectomy
      (LA) and robotic adrenalectomy (RA). METHODS: Using the National Cancer Database,
      we identified patients who underwent LA or RA for nonmetastatic primary adrenal
      malignancy from 2010 to 2013. Primary outcomes were need for open conversion,
      surgical margin status, and performance of regional lymphadenectomy. Secondary
      outcomes were length of stay, readmission, and perioperative mortality. Baseline
      characteristics and outcomes were compared between approaches using the chi
      square, Fisher's exact, and Mann-Whitney U tests. RESULTS: Two hundred thirty
      eight (82%) LA and 51 (18%) RA cases were identified. The LA and RA groups did
      not show any significant differences in terms of patient age, gender, race,
      Charlson score, tumor laterality, size (median 4.2-9.0 cm), histology, grade,
      hospital type, and case volume. The rate of open conversion was 5.9% for RA
      versus 17.2% for LA (P = .04). There were no significant differences in rates of
      positive margins, lymphadenectomy, inpatient stay, readmission, or mortality.
      CONCLUSION: RA significantly decreases need for open conversion compared to LA.
      Although RA improves technical feasibility, the oncological adequacy of minimally
      invasive resection remains uncertain.

PMID- 30196069
TI  - Comparative transcriptome analysis of hESC- and iPSC-derived corneal endothelial
      cells.
AB  - The corneal endothelium (CE), a monolayer of hexagonal cells constitutes the
      innermost layer of the cornea that is critical in maintaining clarity by
      mediating hydration through barrier and pump functions. Corneal endothelial cells
      (CECs) have limited proliferative potential and therefore generation of CECs has
      been undertaken by many groups. We previously reported generation of CECs from
      peripheral blood mononuclear cell (PBMC)-originated, induced pluripotent stem
      cells (iPSCs). In here, we extend our analysis through next-generation seqeuncing
      based transcriptome profiling of H9 human embryonic stem cell (hESC)- and human
      PBMC-originated, iPSC-derived CECs. The differentiating CECs on day 20 (D20)
      exhibited a tightly packed hexagonal/polygonal shape expressing zona occludens-1
      (ZO-1) and N-cadherin at the cell boundaries. Next-generation RNA sequencing of
      hESC- and iPSC-derived CECs detected expression (>=0.659 RPKM) of 13,546 and
      13,536 genes, respectively. Comparative transcriptome analysis of hESC- and iPSC
      derived CECs revealed 13,208 (>96%) genes common in both transcriptomes. Among
      the 13,208 genes common in these transcriptomes, 12,580 (>95%) exhibited a
      quantitatively similar expression. To the best of our knowledge, this is the
      first report presenting comparative transcriptome analysis of hESC- and iPSC
      derived CECs.

PMID- 30196070
TI  - Pathophysiology and inhibition of IL-23 signaling in psoriatic arthritis: A
      molecular insight.
AB  - Psoriatic arthritis (PsA) is a chronic inflammatory arthritis of unknown
      etiology, and currently the cellular and molecular interactions that dictate its
      pathogenesis remain elusive. A role of the interleukin-23 (IL-23)/IL-23R (IL-23
      receptor) interaction in the development of psoriasis and PsA is well
      established. As IL-23 regulates the differentiation and activation of innate and
      adaptive immunity, it pertains to a very complex pathophysiology involving a
      plethora of effectors and transducers. In this review, we will discuss recent
      advances on the cellular and molecular pathophysiological mechanisms that
      regulate the initiation and progression of PsA as well as new therapeutic
      approaches for IL-23/IL-23R targeted therapeutics.

PMID- 30196071
TI  - Comparison of New Glucose-Lowering Drugs on Risk of Heart Failure in Type 2
      Diabetes: A Network Meta-Analysis.
AB  - OBJECTIVES: The authors conducted a systematic review and network meta-analysis
      of placebo-controlled, randomized clinical trials in the post-Food and Drug
      Administration (FDA) guidance era to formally compare the effects of 3 new
      classes of glucose-lowering drugs on hospitalization for heart failure (HF) in
      type 2 diabetes mellitus. BACKGROUND: The 2008 FDA Guidance for Industry launched
      an era of cardiovascular outcome trials for new glucose-lowering drugs in T2DM,
      including glucagon-like peptide (GLP)-1 agonists, dipeptidyl peptidase (DPP)-4
      inhibitors, and sodium glucose co-transporter (SGLT)-2 inhibitors. METHODS: We
      searched Embase, PubMed, Cochrane Library, and clinicaltrials.gov between
      December 1, 2008, and November 24, 2017, for randomized placebo-controlled
      trials, and performed network meta-analyses by Bayesian approach using Markov
      chain Monte Carlo simulation method to compare the effects of glucose-lowering
      drugs on risk of HF hospitalization and estimate the probability that each
      treatment is the most effective. RESULTS: Nine studies were identified, yielding
      data on 87,162 participants. In the network meta-analysis, SGLT-2 inhibitors
      yielded the greatest risk reduction for HF hospitalization compared with placebo
      (relative risk [RR]: 0.56; 95% CrI [credibility interval]: 0.43 to 0.72).
      Moreover, SGLT-2 inhibitors were associated with significant risk reduction in
      pairwise comparisons with both GLP-1 agonists (RR: 0.59; 95% CrI: 0.43 to 0.79)
      and DPP-4 inhibitors (RR: 0.50; 95% CrI: 0.36 to 0.70). Ranking of the classes
      revealed 99.6% probability of SGLT-2 inhibitors being the optimal treatment for
      reducing the risk of this outcome, followed by GLP-1 agonists (0.27%) and DPP-4
      inhibitors (0.1%). CONCLUSIONS: Current evidence suggests that SGLT-2 inhibitors
      are more effective than either GLP-1 agonists or DPP-4 inhibitors for reducing
      the risk of hospitalization for HF in type 2 diabetes mellitus.

PMID- 30196072
TI  - Walking Away From Heart Failure.

PMID- 30196074
TI  - Preventing Heart Failure in Diabetes: Glycemic Targets or Class Effect?

PMID- 30196073
TI  - Physical Activity and Incidence of Heart Failure in Postmenopausal Women.
AB  - OBJECTIVES: This study prospectively examined physical activity levels and the
      incidence of heart failure (HF) in 137,303 women, ages 50 to 79 years, and
      examined a subset of 35,272 women who, it was determined, had HF with preserved
      ejection fraction (HFpEF) and HF with reduced EF (HFrEF). BACKGROUND: The role of
      physical activity in HF risk among older women is unclear, particularly for
      incidence of HFpEF or HFrEF. METHODS: Women were free of HF and reported ability
      to walk at least 1 block without assistance at baseline. Recreational physical
      activity was self-reported. The study documented 2,523 cases of total HF, and 451
      and 734 cases of HFrEF and HFpEF, respectively, during a mean 14-year follow-up.
      RESULTS: After controlling for age, race, education, income, smoking, alcohol,
      hormone therapy, and hysterectomy status, compared with women who reported no
      physical activity (reference group), inverse associations were observed across
      incremental tertiles of total physical activity for overall HF (hazard ratio
      [HR]: Tertile 1 = 0.89, Tertile 2 = 0.74, Tertile 3 = 0.65; trend p < 0.001),
      HFpEF (HR: 0.93, 0.70, 0.68; p < 0.001), and HFrEF (HR: 0.81, 0.59, 0.68; p =
      0.01). Additional controlling for potential mediating factors included attenuated
      time-varying coronary heart disease (CHD) (nonfatal myocardial infarction,
      coronary revascularization) diagnosis but did not eliminate the inverse
      associations. Walking, the most common form of physical activity in older women,
      was also inversely associated with HF risks (overall: 1.00, 0.98, 0.93, 0.72; p <
      0.001; HFpEF: 1.00, 0.98, 0.87, 0.67; p < 0.001; HFrEF: 1.00, 0.75, 0.78, 0.67; p
      = 0.01). Associations between total physical activity and HF were consistent
      across subgroups, defined by age, body mass index, diabetes, hypertension,
      physical function, and CHD diagnosis. Analysis of physical activity as a time
      varying exposure yielded findings comparable to those of baseline physical
      activity. CONCLUSIONS: Higher levels of recreational physical activity, including
      walking, are associated with significantly reduced HF risk in community-dwelling
      older women.

PMID- 30196075
TI  - Ent-kaurane diterpenoids from the cherries of Coffea arabica.
AB  - Four new rearranged ent-kaurane diterpenoids named as caffruenol A (1),
      caffruenol B (2), caffruolide A (3), caffruolide B (4), along with eleven known
      analogues (5-15) were isolated from the cherries of Coffea arabica. The
      structures of new compounds were elucidated by extensive spectroscopic analysis
      and X-ray crystallography. Coffruenols A and B (1 and 2) possessed an ent-4(18)
      kaurene framework and might play an important role on the biosynthesis of the
      rearranged diterpenes that occurred in C. arabica. Moreover, inhibitory effects
      of compounds 1-4 on nitric oxide (NO) production in lipopolysaccharide-activited
      RAW 264.7 macrophages were evaluated.

PMID- 30196076
TI  - Dictyoptesterols A-C, ?22-24-oxo cholestane-type sterols with potent PTP1B
      inhibitory activity from the brown alga Dictyopteris undulata Holmes.
AB  - Three new cholestane-type sterols bearing an unusual ?22-24-oxo side chain,
      namely, dictyoptesterols A-C (1-3), were isolated from the brown alga
      Dictyopteris undulata Holmes, together with five known strutural analogues (4-8).
      Their structures were elucidated on the basis of by extensive spectroscopic
      analysis. The absolute configurations of the steroidal nuclei of the new
      compounds were proposed by a comparison of NMR data with those of related known
      compounds as well as biogenetic considerations. All of the isolates were
      evaluated in vitro for their potential to inhibit protein tyrosine phosphatase-1B
      (PTP1B) activity. The results showed that compounds 1-5 exhibited different
      levels of PTP1B inhibitory activities with IC50 values ranging from 3.03 +/- 0.76
      to 15.01 +/- 2.88 MUM. In particular, compounds 3 and 4 showed promising
      inhibitory effects towards PTP1B with IC50 values of 3.03 +/- 0.76 and 3.72 +/-
      0.40 MUM, respectively, when compared to the positive control oleanolic acid
      (IC50, 2.83 +/- 0.39 MUM). The chemotaxonomic significance of these isolated ?22
      24-oxo cholestanes has also been discussed.

PMID- 30196077
TI  - Predicting subcellular localization of multi-label proteins by incorporating the
      sequence features into Chou's PseAAC.
AB  - The emergence of numerous genome projects has made the experimental
      classification of the protein localization almost impossible due to the
      exponential increase in the number of protein samples. However, most of the
      applications are merely developed for single-plex and completely ignored the
      presence of one protein at two or more locations in a cell. In this regard, few
      attempts were carried out to target Multi-label protein localizations;
      consequently, undesirable accuracies are achieved. This paper presents a novel
      approach, in which a discrete feature extraction method is fused with
      physicochemical properties of amino acids by using Chou's general form of Pseudo
      Amino Acid Composition. The technique is tested on two benchmark datasets namely:
      Gpos-mploc and Virus-mPLoc. The empirical results demonstrated that the proposed
      method yields better results via two examined classifiers i.e. ML-KNN and Rank
      SVM. It is established that the proposed model has improved values in all
      performance measures considered for the comparison.

PMID- 30196078
TI  - Identification and expression analysis of miRNA in hybrid snakehead by deep
      sequencing approach and their targets prediction.
AB  - MicroRNAs (miRNAs) play important regulatory roles in numerous biological
      processes, but there is no report on miRNAs of hybrid snakehead. In this study,
      four independent small RNA libraries were constructed from the spleen, liver
      kidney and muscle of hybrid snakehead. These libraries were sequenced using deep
      sequencing technology, as result, a total of 1,067,172, 1,152,002, 1,653,941 and
      970,866 clean reads from these four libraries were obtained. 252 known miRNAs and
      63 putative novel miRNAs in these small RNA dataset were identified. The stem
      loop RT-qPCR analysis indicated that eight known miRNAs and two novel miRNAs show
      different expression in eight different kinds of tissues. For better
      understanding the functions of miRNAs, 95,947 predicated target genes were
      analyzed by GO and their pathways, the results indicated that these targets of
      the identified miRNAs are involved in a broad range of physiological functions.

PMID- 30196079
TI  - Safety of the Bacillus thuringiensis-derived Cry1A.105 protein: Evidence that
      domain exchange preserves mode of action and safety.
AB  - The lepidopteran-active Cry1A.105 protein is a chimeric three-domain insecticidal
      toxin with distinct structural domains derived from the naturally occurring
      Cry1Ab, Cry1Ac and Cry1F proteins from the soil bacterium Bacillus thuringiensis
      (Bt). The X-ray crystal structure of the Cry1A.105 tryptic core at 3.0 A
      resolution demonstrates its high structural similarity to the tryptic core of
      Cry1Ac. Bioinformatics analyses demonstrate that Cry1A.105 has no significant
      amino acid sequence similarity to known allergens or mammalian toxins, which is
      the same conclusion reached for its component domains. Like its intact donor
      proteins, Cry1A.105 was heat labile at temperatures >=75  degrees C and degraded
      upon exposure to gastrointestinal proteases. No adverse effects were observed in
      mice when Cry1A.105 was dosed orally at 2451 mg/kg body weight. Therefore, the
      weight of evidence supports that Cry1A.105 is safe for human and animal
      consumption. These results support the conclusion that the safety of a chimeric
      protein for human or animal consumption can be evaluated in the context of the
      safety of its donor proteins.

PMID- 30196080
TI  - LmCht5-1 promotes pro-nymphal molting during locust embryonic development.
AB  - Chitinases, key enzymes involved in degradation of chitin, have been repeatedly
      shown to play an indispensable role during insect post-embryonic molting
      processes at stage transitions. However, how chitinases affect insect embryonic
      development remains to be analyzed. In this study, we investigated the role of
      chitinase 5-1 (LmCht5-1) during embryonic development of the hemimetabolous
      insect Locusta migratoria. LmCht5-1 transcript levels were high in pro-nymphs
      during late embryogenesis. The respective protein localized to both the pro
      nymphal and, to a much lesser extent, the newly formed nymphal cuticle. After
      injection of double stranded RNA against LmCht5-1 into 8 days old embryos, LmCht5
      1 transcripts were strongly reduced. Most of dsLmCht5-1-injected pro-nymphs
      failed to develop to first-instar nymphs and died at or before hatching.
      Histological analyzes showed that degradation of the pro-nymph cuticle was
      blocked in these animals. At the ultra-structural level, we found that LmCht5-1
      was needed for the degradation of the lamellar procuticle, while the separation
      of the procuticle from the epicuticle and epidermis (apolysis) was independent of
      LmCht5-1 function. Taken together, our results indicate that LmCht5-1 and other
      yet unknown degrading enzymes act in parallel at distinct positions of the
      cuticle during molting of the pro-nymph to the first-instar nymph during locust
      embryogenesis.

PMID- 30196081
TI  - Promastigote parasites cultured from the lesions of patients with mucosal
      leishmaniasis are more resistant to oxidative stress than promastigotes from a
      cutaneous lesion.
AB  - Human leishmaniasis caused by Leishmania (Viannia) braziliensis can be presented
      as localized cutaneous leishmaniasis (LCL) or mucosal leishmaniasis (ML).
      Macrophages kill parasites using nitric oxide (NO) and reactive oxygen species
      (ROS). The aim of this study was to evaluate the ability of parasites obtained
      from patients with LCL or ML to produce and resist NO or ROS. Promastigotes and
      amastigotes from LCL or ML isolates produced similar amounts of NO in culture.
      Promastigotes from ML isolates were more resistant to NO and H2O2 than LCL
      parasites in a stationary phase, whereas amastigotes from LCL isolates were more
      resistant to NO. In addition, in the stationary phase, promastigote isolates from
      patients with ML expressed more thiol-specific antioxidant protein (TSA) than LCL
      isolates. Therefore it is suggested that infective promastigotes from ML isolates
      are more resistant to microbicidal mechanisms in the initial phase of infection.
      Subsequently, amastigotes lose this resistance. This behavior of ML parasites can
      decrease the number of parasites capable of stimulating the host immune response
      shortly after the infection establishment.

PMID- 30196082
TI  - Patient-Specific Printed Plates Improve Surgical Accuracy In Vitro.
AB  - PURPOSE: It remains unclear to what extent patient-specific printed plates can
      improve surgical outcomes in orthognathic procedures. This study aimed to
      quantify the surgical accuracy of patient-specific printed plates in vitro and to
      compare the results with patients' actual surgical outcomes. PATIENTS AND
      METHODS: This in vitro study enrolled 20 postoperative orthognathic surgical
      patients, all treated with inferior maxillary repositioning. The preoperative
      midfaces were re-created in a 3-dimensionally printed model. The osteotomy and
      screw holes were placed at prespecified positions using a 3-dimensional guide.
      The dental segment was repositioned by means of the patient-specific plates. The
      primary outcome was the mean reposition at 3 dental reference points. The primary
      predictor variable was the obtained surgical reposition in vitro compared with
      the virtual surgical plan. Confounding variables were gender, age, occlusion, and
      bimaxillary surgery. The secondary outcome was surgical accuracy, and the
      secondary predictor was the in vitro outcomes versus the patients' surgical
      outcomes. Surgical accuracy was defined as the difference between the obtained
      reposition and the virtual surgical plan on a continuous scale. The differences
      were recorded in 3 dimensions according to the positive value of the 3 axes:
      right, anterior, and posterior. The results were analyzed using mixed-model
      regression and 1-sample t tests. RESULTS: In the 20 patients (age, 18 to 64
      years; 40% of patients were women), the mean planned reposition was 2.9 mm
      anterior and 1.8 mm inferior. In all models, the osteotomy edge was rounded off
      to position the plate in the predetermined position. Overall, the maxilla was
      positioned 0.5 mm anterior and 0.3 mm inferior to the planned position using
      patient-specific plates. CONCLUSIONS: The patient-specific plates positioned the
      maxilla in close approximation to the planned position without surgically
      relevant differences. The osteotomy edge must be carefully inspected for
      interference with the patient-specific plates to avoid displacement of the
      planned maxillary repositioning.

PMID- 30196083
TI  - Palatal Basal Cell Adenocarcinoma From Misdiagnosis to Cure: A Unique Case Report
      and Review.
AB  - We describe a 66-year-old woman who received a misdiagnosis of benign neoplasms
      twice before receiving the appropriate diagnosis of basal cell adenocarcinoma. At
      the time of recurrence, her care was assumed by the senior author, who made the
      appropriate diagnosis and administered treatment including transoral
      microvascular reconstruction, as well as adjuvant radiation therapy, which
      achieved a cure. A review of the current literature on this disease entity also
      is included.

PMID- 30196084
TI  - The scent of security: Odor of romantic partner alters subjective discomfort and
      autonomic stress responses in an adult attachment-dependent manner.
AB  - When in a stressful situation, access to adult attachment figures (e.g., romantic
      partners) is an important means by which adults regulate stress responses. The
      practice of smelling a partner's worn garment is reported as a self-treatment
      against stress. Here, we experimentally determined whether exposure to a
      partner's body odor attenuates adults' subjective discomfort and
      psychophysiological responses, and whether such effects are qualified by adult
      attachment security. In a blocked design, participants (N = 34) were presented
      with their partner's body odor, their own body odor, the odor of a clean t-shirt
      and rose odor, while exposed to weak electric shocks to induce discomfort and
      stress responses. Results showed that partner body odor reduces subjective
      discomfort during a stressful event, as compared with the odor of oneself. Also,
      highly secure participants had attenuated skin conductance when exposed to
      partner odor. We conclude that partner odor is a scent of security, especially
      for attachment-secure adults.

PMID- 30196085
TI  - Social instability in female rodents as a model of stress related disorders: A
      systematic review.
AB  - The risk of developing stress related disorders such as depression is two times
      higher in women than in men, and social stress is considered the principal
      etiology for this disorder. Social defeat animal model is the most common
      procedure to induce social stress in male rodents, but the stressful stimulus and
      the stress response can be different for each sex. In this regard, social defeat
      stress model does not fit the social nature of females, and according to the
      emerging evidence, the social instability stress (SIS) model could be a suitable
      procedure to investigate this stress related disorder in females. This study aims
      to systematically review the effects of SIS on physiological and behavioral
      parameters involved in the pathophysiology of depression, following the Preferred
      Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method on
      PubMed, Medline and Web of Science. Seventeen studies met the inclusion criteria.
      The reported physiological measures comprised the hypothalamic-pituitary-adrenal
      axis activity, neurotrophic factors, immune and monoaminergic systems,
      vasopressin and oxytocin receptors, sex hormone levels and estrus cycle, while
      main behavioral measures involved sucrose preference test, forced swimming test,
      elevated plus maze, open field test and social interaction. This systematic
      review revealed a wide variability on the social instability regimen and on the
      measured variables. However, all studies agree that SIS model can elicit
      behavioral and physiological alteration involved in stress related disorders,
      with HPA axis hyperactivity, increased anxiety-like behavior and disrupted reward
      system being the most repeated outcomes. A unified SIS application criterion is
      required in order to obtain consistent data and elucidate the underlying
      mechanisms of anxiety and depression in females.

PMID- 30196086
TI  - Neural responses to familiar conspecifics are modulated by a nonapeptide receptor
      in a winter flocking sparrow.
AB  - The social behavior network, a collection of reciprocally connected areas within
      the basal forebrain and midbrain, plays a conserved role in the regulation of
      vertebrate social behavior. Specific behaviors are associated with patterns of
      activity across the network, and these activity profiles vary with species and
      context. We investigated how the social behavior network responds to familiar
      social stimuli in a seasonally flocking songbird. Further, we explored how
      socially-induced neural responses are modulated by endogenous nonapeptide
      receptor blockade. Winter flocking dark-eyed juncos were exposed to either
      familiar conspecifics or a familiar empty aviary following a peripheral injection
      of either saline or [desGly-NH2,d(CH2)5, Tyr(Me)2,Thr4]-ornithine vasotocin, an
      VT3 receptor antagonist. Socially-exposed animals exhibited greater Fos induction
      across the social behavior network. Sex and drug effects were site-specific, with
      females tending to exhibit greater Fos responses to social stimuli and a greater
      sensitivity to VT3 antagonism. We suggest that in flocking animals, VT3
      activation during social interaction may shift the pattern of neural activity
      towards the dorsocaudal lateral septum and rostral arcopallium and away from the
      extended amygdala, anterior and ventromedial hypothalamus, and the caudal
      ventral/ventrolateral lateral septum.

PMID- 30196088
TI  - Postnatal overnutrition alters the orexigenic effects of melanin-concentrating
      hormone (MCH) and reduces MCHR1 hypothalamic expression on spontaneous feeding
      and fasting.
AB  - One of the approaches to induce obesity in rodents consists in reducing litter
      size to 3 pups during the lactation period. Animals submitted to this
      manipulation are heavier, hyperphagic and develop several metabolic diseases for
      the rest of their lives. In the present study, under the premise that melanin
      concentrating hormone (MCH), an orexigenic peptide synthesized by neurons of the
      lateral hypothalamus, is involved in food intake regulation, we aimed to measure
      the hypothalamic expression of its receptor, MCHR1, in adult early overfed obese
      animals and normoweight controls at both ad libitum and food deprived conditions.
      Additionally, we administered MCH, or an antiMCH antibody, into the third
      ventricle of ad libitum-fed rats, or fasted rats, respectively, and evaluated
      chow consumption. Typical nocturnal hyperphagia in rodents was elevated in obese
      animals compared to normoweight controls, accompanied by a lower expression of
      MCHR1 and leptin receptor (Ob-R). Following a 24 h fasting, MCHR1 remained lower
      in SL rats. After 4 h of re-feeding, obese animals ate more than normoweight
      controls. MCH failed to enhance appetite in early overfed obese animals and
      immunoneutralization of the peptide only reduced fasted induced-hyperphagia in
      normoweight controls. These results support the notion that both peptide and
      brain endogenous MCH exert a physiological relevant action in food intake
      regulation in normoweight rats, but that postnatal overnutrition disturbs this
      system, as reflected by MCHR1 downregulation at both ad libitum and fasted
      conditions and in the lack of response to MCH in both positive- and negative
      energetic states in early overfed obese animals.

PMID- 30196087
TI  - Methamphetamine self-administration in a runway model of drug-seeking behavior in
      male rats.
AB  - Cocaine administration has been shown to produce immediate positive (rewarding)
      and subsequent negative (anxiogenic) effects in humans and animals. These dual
      and opposing affective responses have been more difficult to demonstrate with
      administration of methamphetamine (meth). While animal studies have reliably
      demonstrated the positive reinforcing effects of the drug, reports of negative
      aftereffects following acute exposure have been few in number and contradictory
      in nature. The current research was devised to assess the effects of acute meth
      using a runway model of self-administration that is uniquely sensitive to both
      the positive and negative effects of a drug reinforcer in the same animal on the
      same trial. Male rats were allowed to traverse a straight alley once a day for 16
      consecutive days/trials where entry into the goal box resulted in a single IV
      injection of meth (0.25, 0.5 or 1.0 mg/kg/inj.). The chosen doses were confirmed
      to be psychoactive as they produced dose-dependent increases in motoric/locomotor
      activation in these same subjects. The results demonstrated a U-shaped dose
      response curve for the reinforcing effects of meth in that the intermediate dose
      group (0.5 mg/kg) produced the strongest approach behavior in the runway. Unlike
      other psychomotor stimulants, like cocaine, animals running for IV meth exhibited
      no evidence of any significant approach-avoidance behaviors reflective of the
      drug's negative anxiogenic effects. These results suggest that the abuse
      potential for meth is likely higher than for other shorter-acting psychomotor
      stimulants and reaffirms the utility of the runway procedure as a screen for a
      substance's abuse potential.

PMID- 30196089
TI  - Dilatational force in percutaneous tracheostomy : how much is too much?

PMID- 30196090
TI  - Dual epidural catheters for acute pain management of a patient with rib and
      tibial plateau fractures.

PMID- 30196091
TI  - Bellagio Declaration on high-quality health systems: from a quality moment to a
      quality movement.

PMID- 30196092
TI  - Embedding quality at the core of universal health coverage in South Africa.

PMID- 30196094
TI  - Raising a mirror to quality of care in Tanzania: the five-star assessment.

PMID- 30196093
TI  - High-quality health systems in the Sustainable Development Goals era: time for a
      revolution.

PMID- 30196095
TI  - Quality governance in a pluralistic health system: Mexican experience and
      challenges.

PMID- 30196096
TI  - How could health care be anything other than high quality?

PMID- 30196097
TI  - Envisioning a high-quality health system in Nepal: if not now, when?

PMID- 30196098
TI  - Mitochondrial dysfunction caused by m.2336T>C mutation with hypertrophic
      cardiomyopathy in cybrid cell lines.
AB  - Hypertrophic cardiomyopathy (HCM), affecting approximately 1 in 500 in the
      general population, is the most prominent cause of sudden heart disease-related
      mortality in the young. Mitochondrial DNA (mtDNA) mutations are among the primary
      causes of HCM. We previously identified a novel m.2336T>C homoplasmic mutation in
      the mitochondrial 16S rRNA gene (MT-RNR2) in a Chinese maternally inherited HCM
      family. However, the molecular mechanisms by which m.2336T>C mutation contributes
      to HCM remain elusive. Here we generated transferring mitochondria cell lines
      (cybrids) with a constant nuclear background by transferring mitochondria from
      immortalized lymphoblastoid cell lines carrying the HCM-associated m.2336T>C
      mutation into human mtDNA-less (rho degrees ) cells. Functional assays showed a
      decreased stability for 16S rRNA and the steady-state levels of its binding
      proteins in the mutant cybrids. This mutation impaired the mitochondrial
      translation capacity and resulted in many mitochondrial dysfunctions, including
      elevation of ROS generation, reduction of ATP production and impairment of
      mitochondrial membrane potential. Moreover, the mutant cybrids had poor
      physiological status and decreased survival ability. These results confirm that
      the m.2336T>C mutation leads to mitochondrial dysfunction and strongly suggest
      that this mutation may play a role in the pathogenesis of HCM.

PMID- 30196099
TI  - Integrated analysis of in vitro data and the adverse outcome pathway framework
      for prioritization and regulatory applications: An exploratory case study using
      publicly available data on piperonyl butoxide and liver models.
AB  - The integration of existing knowledge to support the risk assessment of chemicals
      is an ongoing challenge for scientists, risk assessors and risk managers. In
      addition, European Union regulations limiting the use of new animal testing in
      cosmetics makes already existing information even more valuable. Applying a
      previous SEURAT-1 program framework to derive predictions of in vivo toxicity
      responses for a compound, we selected piperonyl butoxide (PBO) as a case study
      for identification of knowledge and methodology gaps in understanding a
      compound's effects on the human liver. This is investigated through integration
      of data from human in vitro transcriptomics studies, biological pathway analysis,
      chemical and disease associations, and adverse outcome pathway (AOP) information.
      The outcomes of the analysis are used to generate AOPs of liver-related
      endpoints, identifying areas of concern for risk assessors and regulators. We
      demonstrate that integration of data through already existing and publicly
      available tools can produce outcomes comparable to those that may be found
      through more conventional time- and resource-intensive methods. It is also
      expected that, with more refinement, this approach could in the future provide
      evidence to support chemical risk assessment, while also identifying data gaps
      for which additional testing may be needed.

PMID- 30196100
TI  - Generation of a cluster-free Streptomyces albus chassis strains for improved
      heterologous expression of secondary metabolite clusters.
AB  - Natural products are a rich source of potential drugs for many applications.
      Discovery of natural products through the activation of cryptic gene clusters
      encoding their biosynthetic pathways, engineering of those biosynthetic pathways
      and optimization of production yields often rely on the expression of these gene
      clusters in suitable heterologous host strains. Streptomyces albus J1074 provides
      high success rates of heterologous cluster expression with high levels of
      metabolite production, rapid growth and amenability to genetic manipulations.
      Here, we report the construction of S. albus chassis strains optimized for the
      discovery of natural products through heterologous expression of secondary
      metabolite clusters. 15 clusters encoding secondary metabolite biosynthetic
      pathways were deleted in the chromosome of S. albus Del14. This strain provides a
      substantially improved compound detection limit, owing to the lack of native
      secondary metabolites. Furthermore, the production yield of natural products
      heterologously expressed in S. albus Del14 was higher than in commonly used S.
      albus J1074 and S. coelicolor hosts. S. albus strains B2P1 and B4 were generated
      by introduction of additional phage phiC31 attB sites into the chromosome of S.
      albus Del14, allowing integration of up to four copies of a heterologous gene
      cluster. Amplification of gene clusters in the chromosome of the constructed
      strains further improved production yields of the encoded compounds. One cryptic
      cluster from Streptomyces spp. and two clusters from distantly related Frankia
      spp. strains were successfully activated in these new chassis strains, leading to
      the isolation of a new compound fralnimycin.

PMID- 30196101
TI  - Hyaluronan levels are increased systemically in human type 2 but not type 1
      diabetes independently of glycemic control.
AB  - Hyaluronan (HA), an extracellular matrix glycosaminoglycan, is implicated in the
      pathogenesis of both type 1 diabetes (T1D) as well as type 2 diabetes (T2D) and
      has been postulated to be increased in these diseases due to hyperglycemia. We
      have examined the serum and tissue distribution of HA in human subjects with T1D
      and T2D and in mouse models of these diseases and evaluated the relationship
      between HA levels and glycemic control. We found that serum HA levels are
      increased in T2D but not T1D independently of hemoglobin-A1c, C-peptide, body
      mass index, or time since diabetes diagnosis. HA is likewise increased in
      skeletal muscle in T2D subjects relative to non-diabetic controls. Analogous
      increases in serum and muscle HA are seen in diabetic db/db mice (T2D), but not
      in diabetic DORmO mice (T1D). Diabetes induced by the beta-cell toxin
      streptozotozin (STZ) lead to an increase in blood glucose but not to an increase
      in serum HA. These data indicate that HA levels are increased in multiple tissue
      compartments in T2D but not T1D independently of glycemic control. Given that T2D
      but not T1D is associated with systemic inflammation, these patterns are
      consistent with inflammatory factors and not hyperglycemia driving increased HA.
      Serum HA may have value as a biomarker of systemic inflammation in T2D.

PMID- 30196102
TI  - Resolving neuroinflammation, the therapeutic potential of the anti-malaria drug
      family of artemisinin.
AB  - Artemisinin (Qinghaosu) and its semi-synthetic derivatives have been demonstrated
      to alleviate neuroinflammatory response in the central nerve system (CNS). In
      this review, we summarized that artemisinins are capable to treat
      neuroinflammtion-related CNS diseases in both direct (via regulating inflammatory
      process in the CNS, exerting anti-oxidative stress and neuroprotective effect,
      and preventing Abeta accumulation) and indirect (via maintaining BBB integrity,
      suppressing systemic inflammation and alleviating intestinal inflammtion) manner.
      However, the precise mechanism of their anti-neuroinflammatory effects and
      potential neurotoxicity, which hindered further progress in these aspects,
      remains unclear. We suggest that further understanding of the PK/PD properties
      and structure-action relationship of atemisinin and its derivatives will
      facilitate the development of new therapeutics with better curative effects and
      safety.

PMID- 30196103
TI  - Selective serotonin reuptake inhibitors affect structure, function and metabolism
      of skeletal muscle: A systematic review.
AB  - Selective Serotonin Reuptake Inhibitors (SSRIs) may have side effects, such as
      stiffness, tremors and altered tonic activity, as well as an increased risk of
      developing insulin resistance and diabetes mellitus. However, little is known
      about the structural, functional and metabolic changes of skeletal muscle after
      administration of SSRIs. The aim of this systematic review was to explore and
      discuss the effects of SSRIs on skeletal muscle properties described in human and
      rodent studies. A systematic search of PUBMED, SCOPUS, and WEB OF SCIENCE was
      performed. The inclusion criteria were intervention studies in humans and rodents
      that analysed the effects of SSRIs on skeletal muscle properties. The research
      found a total of six human studies, including two randomized controlled trials,
      one non-randomized controlled trial, one uncontrolled before-after study and two
      case reports, and six preclinical studies in rodents. Overall, the studies in
      humans and rodents showed altered electrical activity in skeletal muscle
      function, assessed through electromyography (EMG) and needle EMG in response to
      chronic treatment or local injection with SSRIs. In addition, rodent studies
      reported that SSRIs may exert effects on muscle weight, the number of myocytes
      and the cross-sectional area of skeletal muscle fibre. The results showed effects
      in energy metabolism associated with chronic SSRI use, reporting altered levels
      of glycogen synthase activity, acetyl-CoA carboxylase phosphorylation, citrate
      synthase activity, and protein kinase B Ser phosphorylation. Moreover, changes in
      insulin signalling and glucose uptake were documented. In this context, we
      concluded based on human and rodent studies that SSRIs affect electrical muscle
      activity, structural properties and energy metabolism in skeletal muscle tissue.
      However, these changes varied according to pre-existing metabolic and functional
      conditions in the rodents and humans.

PMID- 30196104
TI  - Modulation of cellular bioenergetics by CO-releasing molecules and NO-donors
      inhibits the interaction of cancer cells with human lung microvascular
      endothelial cells.
AB  - Interactions between cancer cells and the endothelium play a crucial role during
      metastasis. Here we examined the effects of a carbon monoxide-releasing molecule
      (CORM-401) and a nitric oxide donor (PAPA NONOate) given alone or in combination
      on breast cancer cell adhesion and transmigration across the lung microvascular
      endothelium. We further explored whether the effects of CO and NO on cancer
      endothelial cells interactions are linked with changes in cellular bioenergetics
      in breast cancer or endothelial cells. We found that CORM-401 and PAPA NONOate
      alone or in combination markedly decreased transmigration of breast cancer cells
      across human lung microvascular endothelial cells (hLMVEC), while cancer cell
      adhesion to the endothelium was diminished only by a combination of the two
      compounds. In hLMVECs, CORM-401 decreased glycolysis and stimulated mitochondrial
      respiration, while in breast cancer cells CORM-401 decreased both glycolysis and
      mitochondrial respiration. In contrast, PAPA NONOate decreased mitochondrial
      respiration and slightly stimulated glycolysis in both cell lines. When both
      donors were given together, mitochondrial respiration and glycolysis were both
      profoundly inhibited, and cancer-endothelial cells interactions were additively
      suppressed. Intercellular adhesion molecule-1 (ICAM-1), involved in breast cancer
      cell adhesion to hLMVECs, was downregulated by CORM-401 and PAPA NONOate, when
      applied alone, while a combination of both compounds did not cause any
      enhancement of ICAM-1 downregulation. In conclusion, our findings demonstrate
      that CO and NO differently affect cellular bioenergetics of cancer and
      endothelial cells and suggest that this phenomenon may contribute to additive
      anti-adhesive and anti-transmigratory effects of CO and NO. Pharmacological
      attenuation of metabolism represents a novel, effective way to prevent cancer
      cell interactions with the endothelium, that is an energy-demanding process.

PMID- 30196105
TI  - Familial risk of pleural mesothelioma increased drastically in certain
      occupations: A nationwide prospective cohort study.
AB  - OBJECTIVE: We aimed to explore the effect of occupation on familial risk of
      pleural mesothelioma in a nationwide cohort study design. METHOD: The nationwide
      Swedish Family-Cancer Database includes all Swedes born after 1931 and their
      biological parents, totalling 16.1 million individuals with about 2.3 million
      cancer patients. Hazards ratios (HRs) were calculated adjusting for age, sex and
      region of residence. RESULTS: Having asbestos-related occupation in the absence
      of family history of mesothelioma increased risk of mesothelioma more than
      threefold (adjusted HR = 3.2, 95% confidence interval [CI]: 3.0-3.5). In those
      who had a history of mesothelioma in their first-degree relatives and an asbestos
      related occupation, risk of mesothelioma dramatically increased compared with
      individuals without such occupations and family history (without chronic
      obstructive pulmonary disease [COPD] HR = 24, 95% CI: 15-39; with COPD 45, 95%
      CI: 15-141). In those who had a family history of mesothelioma and no history of
      an asbestos-related occupation, risk of mesothelioma did not show significant
      increase compared with those who had no family history of mesothelioma and no
      asbestos-related occupation (HR = 1.6; 95% CI: 0.7-3.8). CONCLUSION: First-degree
      relatives of patients with pleural mesothelioma had a drastic risk of developing
      this malignancy in case of certain occupations, which shows a gene-environment
      interaction is probable in risk of mesothelioma.

PMID- 30196106
TI  - An extended phase Ib study of epertinib, an orally active reversible dual
      EGFR/HER2 tyrosine kinase inhibitor, in patients with solid tumours.
AB  - BACKGROUND: Dose-escalation of epertinib (S-222611), a new potent oral EGFR/HER2
      inhibitor, has established a recommended daily dose of 800 mg in patients with
      solid tumours. In this study, we have recruited a larger number of patients to
      assess further the safety, tolerability, pharmacokinetics (PKs) and antitumour
      activity. PATIENTS AND METHODS: Patients with solid tumours expressing EGFR or
      HER2 received a single dose of epertinib at 800 mg on Day 1 to assess PK over 7
      days, followed by continuous once-daily dosing from Day 8. RESULTS: We treated 76
      patients with breast (n = 27), upper gastrointestinal (GI; n = 30), head and neck
      (n = 12) or renal cancers (n = 7). Epertinib was well-tolerated with mostly grade
      I and II adverse events (AEs). The most frequent AE was diarrhoea, which was
      generally manageable with loperamide. The objective response rate (ORR) in
      patients with heavily pretreated breast and upper GI cancers was 16.0% (4 PRs)
      and 8.3% (1CR, 1PR), respectively. All six responding patients had HER2-positive
      tumours; the ORR for HER2-positive breast and upper GI cancer populations was
      19.0% and 20.0%. Partial response in the brain disease of one breast cancer
      patient lasted 7.5 months. CONCLUSION: Once-daily dosing of epertinib at 800 mg
      was well-tolerated and demonstrated promising antitumour activity in patients
      with heavily pretreated HER2-positive breast and upper GI cancer, including those
      with brain metastases. EUDRACT NUMBER: 2009-017817-31.

PMID- 30196107
TI  - The impact of effective systemic therapies on surgery for stage IV melanoma.
AB  - INTRODUCTION: The outcomes of patients with metastatic melanoma have
      significantly improved with the introduction of effective systemic therapies
      (ESTs). The role of surgery in the context of ESTs for stage IV melanoma is
      evolving. We sought to characterise the changing patterns of surgery and
      oncological outcomes in patients with stage IV melanoma treated before and after
      the establishment of ESTs. METHODS: Patients undergoing surgical resection of
      stage IV melanoma were identified from our institutional database from 2003 to
      2015. Patients were grouped into two cohorts, those referred before EST (2003
      2007) and after EST (2011-2015). Clinicopathological variables, patterns of
      surgery and oncological outcomes in the two groups were compared. RESULTS: A
      total of 138 patients underwent surgery for stage IV melanoma (n = 69 in each
      cohort). We observed no significant difference in the ratio of
      operations/patients performed. However, the pattern of operations altered, with a
      significant decrease in in-transit excisions (0.9% vs. 19.4%, p < 0.001) and an
      increase in abdominal metastasectomies (21.1% vs. 4.2%, p < 0.001), in the after
      EST cohort. Novel indications for surgical intervention were noted in the after
      EST cohort, with a significant increase in potentially curative operations for
      residual oligometastatic disease (15.9% vs. 4.3%, p = 0.045). Survival after
      surgery was prolonged in the after-EST cohort (median 16 months vs. 6 months, p <
      0.001), with the stage at initial metastasectomy (stage 4a, hazard ratio [HR]
      0.45 (0.28-0.73), p = 0.001) and treatment with immune checkpoint inhibitors (HR
      0.38 (0.25-0.60), p < 0.001) associated with prolonged survival. DISCUSSION:
      Surgery remains important in the management of stage IV melanoma, with evolving
      indications and patterns of intervention after the introduction of ESTs. The
      combination of judicious surgery and EST may improve oncological outcomes.

PMID- 30196108
TI  - Haematological toxicities with immunotherapy in patients with cancer: a
      systematic review and meta-analysis.
AB  - INTRODUCTION: Programmed cell death-1 or ligand 1 (PD-(L)1) inhibitors are
      associated with immune-related adverse events. Conversely, little is known about
      the incidence of haematological toxicities across published trials. We have
      performed a systematic review and meta-analysis to evaluate the incidence of
      immunotherapy-related anaemia, neutropenia and thrombocytopenia among different
      tumour types, trials phases and anti-PD-(L)1 agents. MATERIAL AND METHODS: A
      PubMed, Embase and Cochrane library search on 23rd December 2017 and a review of
      references from relevant articles were done. Studies regarding haematological
      diseases were excluded. The pooled incidence rates weighted for the individual
      sample sizes were calculated according to fixed or random effect models.
      Incidence of all-grade and grade (G) III or higher anaemia were the primary end
      points. Neutropenia, febrile neutropenia and thrombocytopenia were secondary end
      points. RESULTS: Forty-seven studies of PD-(L)1 inhibitors for a total of 9324
      evaluable patients were included in the meta-analysis. The overall incidence of
      anaemia during PD-(L)1 inhibitor was 9.8% (95% confidence interval [CI], 6-13.6%)
      for all-grade and 5% (95% CI, 3.3-6.7%) for G3-5 anaemia. The incidence was
      higher in diseases different from genitourinary, lung and melanoma, with avelumab
      and in phase II studies. In randomised trials, relative risk of all-grade anaemia
      for patients receiving anti-PD-(L)1 agents compared with control arms was 0.25
      (95% CI, 0.16-0.39; p < 0.001). Incidence of all grades and G3-5 neutropenia and
      thrombocytopenia were 0.94%, 1.07%, 2.8% and 1.8%, respectively. Febrile
      neutropenia was 0.45%. CONCLUSIONS: The incidence of PD-(L)1 inhibitor-related
      anaemia was not negligible. Severe neutropenia, thrombocytopenia and febrile
      neutropenia were rare. These findings are useful for clinicians and suggest that
      blood cell count should be checked before every cycle and support should be given
      when severe toxicity appears.

PMID- 30196109
TI  - Farnesoid X receptor agonist obeticholic acid inhibits renal inflammation and
      oxidative stress during lipopolysaccharide-induced acute kidney injury.
AB  - It is increasingly recognized that farnesoid X receptor (FXR) has anti
      inflammatory and antioxidant activities. The present study investigated the
      effects of obeticholic acid (OCA), a novel synthetic FXR agonist, on renal
      inflammation and oxidative stress in a model of sepsis-induced acute kidney
      injury. All mice except controls were intraperitoneally injected with
      lipopolysaccharide (LPS, 2.0 mg/kg). In the OCA + LPS group, mice were orally
      pretreated with three doses of OCA (5 mg/kg) at 48, 24 and 1 h before LPS
      injection. Interestingly, OCA pretreatment alleviated LPS-induced renal
      dysfunction and pathological damage. Moreover, OCA pretreatment repressed renal
      inflammatory cytokines and chemokines during LPS-induced acute kidney injury. In
      addition, OCA blocked nuclear translocation of nuclear factor kappa B (NF-kappaB)
      p65 and p50 subunits in tubular epithelial cells of renal cortex. Additional
      experiment showed that OCA pretreatment attenuated LPS-induced renal glutathione
      depletion, lipid peroxidation and protein nitration. Moreover, OCA pretreatment
      inhibited the upregulation of renal NADPH oxidase and inos genes during LPS
      induced acute kidney injury. In conclusion, OCA pretreatment protects against
      sepsis-induced acute kidney injury through inhibiting renal inflammation and
      oxidative stress. These results provide evidence for roles of FXR as an important
      regulator of inflammation and oxidative stress in the kidney.

PMID- 30196110
TI  - Effective suppression of donor specific antibody production by Cathepsin S
      inhibitors in a mouse transplantation model.
AB  - Donor-specific antibodies (DSA) are a major risk factor for antibody-mediated
      rejection (ABMR) in solid organ transplantation, and ABMR remains a medical
      challenge. Therefore, effective anti-ABMR therapies are needed to improve overall
      graft survival. Cathepsin S (Cat S) is an essential protease for antigen peptide
      loading onto lysosomal/endosomal major histocompatibility complex (MHC) class II
      molecules to promote antigen presentation. Cat S deficiency produces immuno
      deficient phenotypes including a suppressed humoral immune response, and Cat S
      inhibition reportedly prevents autoimmunity. However, little is known about the
      effects of Cat S inhibitors on organ transplantation, especially ABMR. Here, we
      report the pharmacological profile of novel Cat S inhibitors, AS2761325 and
      AS2863995, and explore their preventive potential on DSA production and acute
      rejection in a mouse cardiac transplantation model. Cat S inhibitors potently
      inhibited upregulation of antigen peptide loading MHC class II expression on the
      surface of splenic B cells and suppressed ovalbumin-induced T cell-dependent
      antibody production in mice. In a mouse cardiac transplantation model, oral
      administration of AS2761325 monotherapy inhibited DSA production without
      affecting graft survival. When combined with a suboptimal dose of tacrolimus,
      AS2761325 significantly prolonged graft survival. The more potent Cat S inhibitor
      AS2863995 also prolonged graft survival and almost completely suppressed DSA
      production. These results suggest that Cat S inhibitors may be promising ABMR
      prophylaxis drug candidates. Combination therapy comprising a Cat S inhibitor and
      calcineurin inhibitors may be a more effective immunosuppressive maintenance
      therapy for controlling both cell-mediated and antibody-mediated rejection.

PMID- 30196111
TI  - A short peptide reverses the aggressive phenotype of prostate cancer cells.
AB  - Previous studies have demonstrated that fibroblast growth factor 8b (FGF8b) is up
      regulated in a large proportion of prostate cancer patients, and plays a key role
      in the aggressive progress of prostate cancer. Herein, we investigated the
      effects of a short peptide derived from the gN helix domain of FGF8b on the
      metastatic behaviors of prostate cancer cells. The results demonstrated that the
      synthetic peptide might reverse the effects of FGF8b on cell proliferation,
      migration and invasion by suppressing the activation of MAPK and Akt signaling
      cascades, and reducing the expressions of the metastasis-related proteins,
      resulting in suppression of the aggressive phenotype of the prostate cancer
      cells. Collectively, these results underline the therapeutic potential of the
      FGF8b mimic peptide in advanced prostate cancer.

PMID- 30196112
TI  - Synthesis and application of sugarcane bagasse cellulose mixed esters. Part I:
      Removal of Co2+ and Ni2+ from single spiked aqueous solutions in batch mode using
      sugarcane bagasse cellulose succinate phthalate.
AB  - Sugarcane bagasse cellulose mixed ester succinate phthalate (SBSPh) was
      synthesized by a novel one-pot reaction method. The effects of temperature, time
      and mole fraction of succinic anhydride (chiSA) on the responses weight gain
      (wg), number of carboxylic acid groups (nT,COOH), and adsorption capacity (q) of
      Co2+ and Ni2+ were evaluated by a 23 experimental design. The chemical structure
      of the material was elucidated by Fourier transform infrared, 13C Multiple Cross
      Polarization solid-state NMR spectroscopy and 1H NMR relaxometry. The best SBSPh
      synthesis condition (100  degrees C, 11 h, chiSA of 0.2) yielded a wg of 59.1%,
      nT,COOH of 3.41 mmol g-1, and values of qCo2+ and qNi2+ of 0.348 and 0.346 mmol g
      1, respectively. The Sips model fitted better the equilibrium data, and the
      maximum adsorption capacities (pH 5.75 and 25  degrees C) estimated by this model
      were 0.62 and 0.53 mmol g-1 for Co2+ and Ni2+, respectively. The DeltaadsH
      degrees  values estimated by isothermal titration calorimetry were 8.43 and 7.79
      kJ mol-1 for Co2+ and Ni2+, respectively. Desorption and re-adsorption
      efficiencies were evaluated by a 22 experimental design, which showed that SBSPh
      adsorbent can be recovered and reused without significant loss of adsorption
      capacity.

PMID- 30196113
TI  - Selective removal of phosphate by dual Zr and La hydroxide/cellulose-based bio
      composites.
AB  - Bimetallic oxides nanocomposites always exhibited the better phosphate capacities
      than those monometallic oxides samples. Herein, the high carbohydrate-content
      biomaterials, shaddock peels (SP), were used as the bio-host for supporting the
      bimetallic oxides, zirconium (Zr) and lanthanum (La) hydroxides, forming the SP
      Zr-La composites. Phosphate adsorption properties as well as stability of the
      novel composites were evaluated. The SP-Zr-La composites indicated that some rod
      like or amorphous nanoparticles with sizes of 20-150 nm were anchored inside the
      SP, which exerted more available interface interactions toward the adsorbed ions.
      The Zr-La species were pH-sensitive and adsorption capacity of phosphate by SP-Zr
      La was increased with the rise in temperature. As the molar ratio of accompanying
      ions/phosphate was increased from 0 to 10 times, the SP-Zr-La was observed with
      the adsorption loss of 27.2-36.7%. Whereas the adsorption loss of cationic SP
      (grafted with quaternary ammonium groups) was calculated up to 86.2-91.6%; this
      indicated the more feasibility of SP-Zr-La in real applications. In addition, the
      stability of impregnated Zr and La species in SP-Zr-La was greatly improved by
      the bio-carrier through the "shielding effect" in a low HA surrounding.

PMID- 30196114
TI  - Adsorption of 17beta-estradiol from aqueous solutions by a novel hierarchically
      nitrogen-doped porous carbon.
AB  - A novel interconnected hierarchically nitrogen-doped porous carbon (IHNPC)
      derived from metal-organic framework-based composites was obtained via a facile
      method and applied as a superior material for the capture of 17beta-estradiol
      (E2) from aqueous solution. The adsorption kinetic and isotherm behaviors were
      well described by the pseudo-second-order and Langmuir models. Various
      thermodynamic parameters uncovered that E2 adsorption onto IHNPC was spontaneous
      and exothermic. Moreover, the adsorption rate of E2 by IHNPC didn't decrease with
      increasing water salinity in the presence of electrolyte ions and humic acids.
      Naturally occurring aquatic particles can enhance (i.e., Al2O3), decrease (i.e.,
      kaolin and SiO2) or have no obvious effects (i.e., montmorillonite) on the
      adsorption rate of E2 by IHNPC. The high adsorption capacity and remarkable
      adsorption selectivity of IHNPC highlighted the application of IHNPC for the
      capture of E2 and provided understanding of the fate and transport of E2 in
      natural aquatic environments.

PMID- 30196116
TI  - Genipin attenuates hyperoxia-induced lung injury and pulmonary hypertension via
      targeting glycogen synthase kinase-3 beta in neonatal rats.
AB  - OBJECTIVES: Bronchopulmonary dysplasia is the most common chronic lung disease of
      infancy and is associated with pulmonary hypertension (PH). Inhibition of
      glycogen synthase kinase (GSK)-3 beta has been shown to attenuate lung injury and
      PH in hyperoxia-exposed newborn rats. Genipin has been widely used for the
      treatment of inflammatory diseases. The aim of this study was to show that
      genipin decreased the expression of GSK-3 beta in lung tissues of hyperoxia
      exposed rat pups. METHODS: We established models of hyperoxia-exposed rat pups,
      evaluated lung injury and pulmonary hypertension and detected the mRNA and
      protein expression of key molecules. RESULTS: Hyperoxia resulted in the reduction
      of survival rate and histologic injury of lung tissues; an increase of the
      messenger RNA (mRNA) expression of transforming growth factor-beta1,
      extracellular matrix proteins collagen-I and fibronectin, and alpha-smooth muscle
      actin; an increase of right ventricular (RV) systolic pressure and the weight
      ratio of RV to left ventriclar (LV) plus septum (S) (RV/LV + S) were inhibited by
      genipin. Genipin also decreased the levels of tumor necrosis factor-alpha,
      interleukin-1 beta, and interleukin-6 in both bronchoalveolar lavage fluid and
      lung tissues after hyperoxia exposure. In addition, genipin inhibited p65 nuclear
      factor-kappaB nuclear translocation and matrix metalloproteinase-2 and -9
      expression. Moreover, hyperoxia resulted in an increase of methane dicarboxylic
      aldehyde content and a decrease of superoxide dismutase activity, catalytic
      subunit of glutamate-cysteine ligase, modified subunit of glutamate-cysteine
      ligase, and nuclear factor erythroid 2-related factor 2 expression were inhibited
      by genipin. All these effects induced by genipin were blocked by upregulation of
      GSK-3 beta. Genipin downregulated GSK-3 beta expression, decreased nuclear factor
      kappaB translocation, increased nuclear factor erythroid 2-related factor 2
      expression, attenuated inflammation and oxidative stress, leading to amelioration
      of lung injury and PH in hyperoxia-exposed rat pups. CONCLUSION: Overall, genipin
      may provide a novel therapeutic option for preventing and treating infants with
      bronchopulmonary dysplasia.

PMID- 30196115
TI  - HeteroMeth: A Database of Cell-to-cell Heterogeneity in DNA Methylation.
AB  - DNA methylation is an important epigenetic mark that plays a vital role in gene
      expression and cell differentiation. The average DNA methylation level among a
      group of cells has been extensively documented. However, the cell-to-cell
      heterogeneity in DNA methylation, which reflects the differentiation of
      epigenetic status among cells, remains less investigated. Here we established a
      gold standard of the cell-to-cell heterogeneity in DNA methylation based on
      single-cell bisulfite sequencing (BS-seq) data. With that, we optimized a
      computational pipeline for estimating the heterogeneity in DNA methylation from
      bulk BS-seq data. We further built HeteroMeth, a database for searching,
      browsing, visualizing, and downloading the data for heterogeneity in DNA
      methylation for a total of 141 samples in humans, mice, Arabidopsis, and rice.
      Three genes are used as examples to illustrate the power of HeteroMeth in the
      identification of unique features in DNA methylation. The optimization of the
      computational strategy and the construction of the database in this study
      complement the recent experimental attempts on single-cell DNA methylomes and
      will facilitate the understanding of epigenetic mechanisms underlying cell
      differentiation and embryonic development. HeteroMeth is publicly available at
      http://qianlab.genetics.ac.cn/HeteroMeth.

PMID- 30196117
TI  - Shorter pregnant women restrained in the rear seat of a car are at risk for
      serious neck injuries: Biomechanical analysis using a pregnant crash test dummy.
AB  - INTRODUCTION: When considering seat belt contacts to the neck in pregnant woman
      of shorter height sitting in the rear seat of a vehicle, subsequent injuries
      after a collision must be understood in the context of both maternal and fetal
      outcomes. To determine likely injuries to a pregnant woman sitting in the rear
      seat, we determined the kinematics of a "pregnant" crash test dummy by measuring
      neck compression forces and biomechanical parameters acting on the head and neck.
      METHODS: Sled tests using a shorter-height pregnant woman crash test dummy
      (Maternal Anthropometric Measurement Apparatus, ver. 2B) were performed at the
      HYGE sled test facility representing full frontal impact at target velocities of
      29km/h and 48km/h. Kinematics of the dummy and biomechanical parameters of the
      head, neck, and chest were measured. Pressure to the neck was measured using
      Prescale (Fujifilm, Tokyo, Japan). RESULTS: During frontal collision tests, the
      shoulder belt compressed the neck at a pressure >12.8MPa, even during the low
      velocity impact. In addition to neck flexion, right side bending and the head and
      chest moving in opposite directions were observed, with maximum differences of
      42.4mm at high velocity and 33.7mm at low velocity. CONCLUSIONS: This study
      provides data on the kinematics of pregnant women of short height sitting in the
      rear seat during a frontal collision using a pregnant woman crash test dummy. The
      knowledge gathered from this study should be useful for determining pregnant
      women passengers' kinematics at the time of collision and evaluating the
      relationship between the vehicle collision and fetal outcomes.

PMID- 30196118
TI  - Ectopic follicular variant of papillary thyroid carcinoma in anterior mediastinum
      with a normal thyroid gland. A case report.
AB  - INTRODUCTION: Ectopic thyroid is rare, especially in the anterior mediastinum.
      Furthermore, true malignant transformation in ectopic location with normal
      orthotopic gland is exceptionally unusual. The authors have tried to put forward
      a challenging case of a malignant mediastinal mass managed successfully via a
      multidisciplinary approach. PRESENTATION OF CASE: We report the case of a 55 year
      old female with ectopic follicular variant of papillary thyroid cancer in the
      anterior mediastinum with no disease in the thyroid gland. Subsequently, complete
      excision of the mediastinal mass and total thyroidectomy was done followed by
      radio-iodine ablation with radiotherapy. Patient showed good uneventful recovery
      and remains tumor free till date. CONCLUSION: The aim of this report is to bring
      forward malignant ectopic thyroid carcinoma as a differential for malignant
      mediastinal masses. It is emphasized that the diagnosis is made essentially
      through physical and pathological examination and, in most cases, only after
      surgery. A Multidisciplinary approach is recommended in such cases.

PMID- 30196119
TI  - An unusual presentation of a papillary thyroid carcinoma in the struma ovarii in
      a 10 year-old girl: A case report.
AB  - INTRODUCTION: Struma ovarii is an ovarian tumor with thyroid tissue as its
      predominant component. It usually occurs in older women and presents with
      abdominal mass, pain and abnormal bleeding. Most patients are euthyroid, but some
      reports have noted thyrotoxicosis originating from the malignant struma ovarii.
      PRESENTATION OF CASE: A 10 year-old girl presented with tachycardia, normal
      thyroid exam and thyrotoxicosis. Thyroid scan showed no uptake with increased
      uptake in right ovary indicative of struma ovarii. The patient underwent
      oophorectomy and thyroidectomy, Pathology showed papillary thyroid carcinoma
      limited to the struma ovarii. Following TSH suppressive therapy and treatment
      with I131, she is totally symptom free. DISCUSSION: Struma ovarii should be a
      possible diagnosis in any female patient with thyrotoxicosis manifestations with
      normal thyroid scan and examination.

PMID- 30196120
TI  - Mathematical models for the effects of hypertension and stress on kidney and
      their uncertainty.
AB  - Determining the future state of individual patients, with regard to the
      susceptibility to life-threatening condition is a crucial problem in the public
      health. Chronic Kidney Disease (CKD) is a perilous disease, which is
      characterized by gradual loss of kidney function. This paper presents a set of
      mathematical models for CKD by applying both deterministic and stochastic
      approaches. Specifically, hypertension and stress are considered as the main
      causes of damaging and removing of nephrons thereby reducing the Glomerular
      Filtration Rate (GFR), which leads to irreparable damages to the kidney function
      and may result in renal failure, or even kidney loss. This paper analyzes the
      equilibria for both deterministic and stochastic models. In this regard,
      mathematical theorems related to stability and stochastic stability of the models
      are provided. The other important issue, which is discussed in the presented
      work, is the uncertainty problem for stochastic models. We have used simulations
      in MATLAB to calculate the uncertainty of the stochastic models. In addition, we
      have provided a framework for the future prediction of proposed models in
      specific cases. Finally, the models and the theoretical results are verified in
      application by applying them to the real clinical data.

PMID- 30196121
TI  - Regulatory T-cell deficiency and autoimmune skin disease: Beyond the scurfy mouse
      and immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome.

PMID- 30196122
TI  - Genetic evidence for the intercontinental movement of avian influenza viruses
      possessing North American-origin nonstructural gene allele B into South Korea.
AB  - Avian influenza viruses (AIVs) are genetically separated by geographical
      barriers, resulting in the independent evolution of North American and Eurasian
      lineages. In the present study, to determine whether AIVs possessing the North
      American-origin nonstructural (NS) gene were previously introduced into South
      Korea, we performed a genetic analysis of AIVs isolated from fecal samples of
      migratory birds. We detected seven viruses possessing the North American-origin
      NS allele B among 413 AIV-positive samples obtained during AI surveillance
      between 2012 and 2017. We found evidence for the intercontinental transmission of
      at least three genetically distinct clusters of the B allele of the North
      American-origin NS gene into Eurasia at a low frequency. The host species of
      three viruses were identified as the greater white-fronted goose (Anser
      albifrons) using a DNA barcoding technique. Moreover, we used GPS-CDMA-based
      telemetry to determine the migration route of the greater white-fronted goose
      between the Far East of Russia and South Korea and found that this species may
      play an important role as an intermediate vector in the intercontinental
      transmission of AIVs. To improve our understanding of the role of wild birds in
      the ecology of AIVs, advanced AIV surveillance is required in the Far East of
      Russia as well as in Alaska region of Beringia accompanied by host identification
      and wild bird tracking.

PMID- 30196123
TI  - Training in aspiration abortion care: An observational cohort study of achieving
      procedural competence.
AB  - BACKGROUND: Studies in multiple countries have found that the provision of
      aspiration abortion care by trained nurses, midwives, and other front-line health
      care workers is safe and acceptable to women. In the United States, most state
      abortion laws restrict the provision of abortion to physicians; nurse
      practitioners, nurse-midwives, and physician assistants, can legally perform
      medication abortion in only twelve states and aspiration abortion in five.
      Expansion of abortion care by these providers, consistent with their scopes of
      practice, could help alleviate the increasing difficulty of accessing abortion
      care in many states. OBJECTIVES: This study used a competency-based training
      model to teach advanced practice clinicians to perform vacuum aspiration for the
      abortion care. Previous research reporting on the training of providers other
      than physicians primarily focused on numbers of procedures performed, without
      assessment of skill competency or clinician confidence. DESIGN: In this
      prospective, observational cohort study, advanced practice clinician trainees
      were recruited from 23 clinical sites across six partner organizations. Trainees
      participated in a standardized, competency-based didactic and clinical training
      program in uterine aspiration for first-trimester abortion. SETTINGS: Trainee
      clinicians needed to be employed by one of the six partner organizations and have
      an intention to remain in clinical practice following training. PARTICIPANTS:
      California-licensed advanced practice clinicians were eligible to participate in
      the training if they had at least 12 months of clinical experience, including at
      least three months of medication abortion provision, and certification in Basic
      Life Support. METHODS: A standardized, competency-based training program
      consisting of both didactic and clinical training in uterine aspiration for first
      trimester abortion was completed by 46 advanced practice clinician participants.
      Outcomes related to procedural safety and to the learning process were measured
      between August 2007 and December 2013, and compared to those of resident
      physician trainees. RESULTS: Essentially identical odds of complications
      occurring from advanced practice clinician-performed procedures were not
      significantly different than the odds of complications occurring from resident
      performed procedures (OR: 0.99; CI: 0.46-2.02; p > 0.05) after controlling for
      patient sociodemographic and medical history. The number of training days to
      foundational competence ranged from six to 10, and the number of procedures to
      competence for those who completed training ranged from 40 to 56 (median = 42.5).
      CONCLUSIONS: A standardized, competency-based trainingprogram can prepare
      advanced practice clinicians to safely provide first-trimester aspiration
      abortions. Access to safe abortion care can be enhanced by increasing the number
      of providers from cadres of clinicians other than physicians.

PMID- 30196124
TI  - Reply to assessing usefulness of GlideScope(r) video laryngoscope in children
      with difficult direct laryngoscopy.

PMID- 30196125
TI  - Inward rectifier potassium (Kir) channels in the soybean aphid Aphis glycines:
      Functional characterization, pharmacology, and toxicology.
AB  - Inward rectifier K+ (Kir) channels contribute to a variety of physiological
      processes in insects and are emerging targets for insecticide development.
      Previous studies on insect Kir channels have primarily focused on dipteran
      species (e.g., mosquitoes, fruit flies). Here we identify and functionally
      characterize Kir channel subunits in a hemipteran insect, the soybean aphid Aphis
      glycines, which is an economically important insect pest and vector of soybeans.
      From the transcriptome and genome of Ap. glycines we identified two cDNAs, ApKir1
      and ApKir2, encoding Kir subunits that were orthologs of insect Kir1 and Kir2,
      respectively. Notably, a gene encoding a Kir3 subunit was absent from the
      transcriptome and genome of Ap. glycines, similar to the pea aphid Acyrthosiphon
      pisum. Heterologous expression of ApKir1 and ApKir2 in Xenopus laevis oocytes
      enhanced K+-currents in the plasma membrane; these currents were inhibited by
      barium and the small molecule VU041. Compared to ApKir2, ApKir1 mediated currents
      that were larger in magnitude, more sensitive to barium, and less inhibited by
      small molecule VU041. Moreover, ApKir1 exhibited stronger inward rectification
      compared to ApKir2. Topical application of VU041 in adult aphids resulted in dose
      dependent mortality within 24 h that was more efficacious than flonicamid, an
      established insecticide also known to inhibit Kir channels. We conclude that
      despite the apparent loss of Kir3 genes in aphid evolution, Kir channels are
      important to aphid survival and represent a promising target for the development
      of new insecticides.

PMID- 30196126
TI  - Validation of antibody-based tools for galanin research.
AB  - Antibodies are an integral biomedical tool, not only for research but also as
      therapeutic agents. However, progress can only be made with sensitive and
      specific antibodies. The regulatory (neuro)peptide galanin and its three
      endogenous receptors (GAL1-3-R) are widely distributed in the central and
      peripheral nervous systems, and in peripheral non-neuronal tissues. The galanin
      system has multiple biological functions, including feeding behavior, pain
      processing, nerve regeneration and inflammation, to name only a few. Galanin
      could serve as biomarker in these processes, and therefore its receptors are
      potential drug targets for various diseases. For that reason, it is of paramount
      interest to precisely measure galanin peptide levels in tissues and to determine
      the cellular and subcellular localization of galanin receptors. A plethora of
      antibodies and antibody-based tools, including radioimmunoassay (RIA) and enzyme
      linked immunosorbent assay (ELISA) kits, are commercially available to detect
      galanin and its receptors. However, many of them lack rigorous validation which
      casts doubt on their specificity. A goal of the present study was to raise
      awareness of the importance of validation of antibodies and antibody-based tools,
      with a specific focus on the galanin system. To that end, we tested and report
      here about commercially available antibodies against galanin and galanin
      receptors that appear specific to us. Furthermore, we investigated the validity
      of commercially available galanin ELISA kits. As the tested ELISAs failed to meet
      the validation requirements, we developed and validated a specific sandwich ELISA
      which can be used to detect full-length galanin in human plasma.

PMID- 30196127
TI  - Making protocols available with the article improved evaluation of selective
      outcome reporting.
AB  - OBJECTIVE: To compare primary outcomes reported in publications, protocols and
      registries and to evaluate the contribution of available protocols to assess
      selective outcome reporting (SOR) as compared with registration alone. STUDY
      DESIGN AND SETTING: We included all randomized controlled trials (RCTs) published
      in 2015 and 2016 in the five leading general medical journals. For each RCT, we
      evaluated whether the protocol was available and searched for registration. We
      extracted all primary outcomes reported in publications, registries, and
      protocols. We evaluated whether SOR was suspected (i.e., at least one discrepancy
      in primary outcomes), unclear, or not suspected based on comparisons of
      publications and (1) trial registration alone or (2) protocols in addition to
      registration. RESULTS: Selective outcome reporting was suspected for 77/274
      (28.1%), unclear for 30 (10.9%), and not suspected for 167 (60.9%) when comparing
      publications and trial registration alone. With protocols available, the
      classification changed for 38 RCTs (13.9%): 11 not suspected of SOR based on
      registration became suspected of SOR with protocols available, and 27 with
      unclear assessment based on registration became suspected of SOR (n = 7) and not
      suspected of SOR (n = 20) with protocols available. CONCLUSIONS: Compared to
      registration alone, making protocols available allows for a more precise
      evaluation of SOR.

PMID- 30196128
TI  - A Web-based survey among adults aged 40-54 years was time effective and yielded
      stable response patterns.
AB  - OBJECTIVE: We want to present information about response patterns obtained by Web
      based survey in a large-scale epidemiological study. STUDY DESIGN AND SETTING:
      Within the RAPS (Risk Adapted Prevention Strategies for colorectal cancer [CRC])
      study, we invited 160,000 randomly selected persons aged 40-54 years in three
      large German cities from 2015 to 2016 to complete a Web-based questionnaire on
      CRC risk factors and screening (97 items, average time for completion 15
      minutes). Invitation letters and up to two reminder letters were sent to each
      individual. RESULTS: A total of 21.4% of women and 18.0% of men completed the
      questionnaire. Overall cumulative response rates were 7.5%, 14.3%, and 19.6%
      after the initial invitation letter, and the first and second reminder,
      respectively, with prevalence of and associations of key epidemiological
      parameters (such as family history of cancer, previous colonoscopy, etc.) being
      remarkably stable across waves of responses. For example, the sex and age
      distribution of the sample did not change with additional answers gained from
      additional letters. CONCLUSION: Web-based questionnaires are feasible, cost
      effective, and time effective in the setting of large-scale epidemiological
      studies. Although response patterns were remarkably stable over several rounds of
      reminders with substantially increasing cumulative response rates, future
      research should address possibilities to further enhance response rates.

PMID- 30196129
TI  - Lack of transparency in reporting narrative synthesis of quantitative data: a
      methodological assessment of systematic reviews.
AB  - OBJECTIVE: To assess the adequacy of reporting and conduct of narrative synthesis
      of quantitative data (NS) in reviews evaluating the effectiveness of public
      health interventions. STUDY DESIGN AND SETTING: A retrospective comparison of a
      20% (n = 474/2,372) random sample of public health systematic reviews from the
      McMaster Health Evidence database (January 2010-October 2015) to establish the
      proportion of reviews using NS. From those reviews using NS, 30% (n = 75/251)
      were randomly selected and data were extracted for detailed assessment of:
      reporting NS methods, management and investigation of heterogeneity, transparency
      of data presentation, and assessment of robustness of the synthesis. RESULTS:
      Most reviews used NS (56%, n = 251/446); meta-analysis was the primary method of
      synthesis for 44%. In the detailed assessment of NS, 95% (n = 71/75) did not
      describe NS methods; 43% (n = 32) did not provide transparent links between the
      synthesis data and the synthesis reported in the text; of 14 reviews that
      identified heterogeneity in direction of effect, only one investigated the
      heterogeneity; and 36% (n = 27) did not reflect on limitations of the synthesis.
      CONCLUSION: NS methods are rarely reported in systematic reviews of public health
      interventions and many NS reviews lack transparency in how the data are presented
      and the conclusions are reached. This threatens the validity of much of the
      evidence synthesis used to support public health. Improved guidance on reporting
      and conduct of NS will contribute to improved utility of NS systematic reviews.

PMID- 30196130
TI  - Non-ataxic manifestations of Spinocerebellar ataxia-2, their determinants and
      predictors.
AB  - INTRODUCTION: To evaluate the non-ataxic clinical manifestations in genetically
      proven Spinocerebellar ataxia 2 (SCA2) and identify their determinants and
      predictors. METHODS: Seventy-three subjects with genetically proven SCA2 were
      evaluated clinically for the common non-ataxic manifestations. Based on the
      presence or absence of non-ataxic manifestations, patients were classified into
      groups and then compared for significant differences in the CAG repeat length,
      age at onset (AAO), duration of disease, and ataxia rating score. Predictors of
      non-ataxic symptoms were identified using multivariable binary logistic
      regression. RESULTS: The most common non-ataxic clinical manifestations were
      peripheral neuropathy, extrapyramidal features, pyramidal signs, cognitive
      impairment and lower motor neuron signs. The CAG repeat length was inversely
      related to the AAO of symptoms (r = -0.46, p < .001). Patients with peripheral
      neuropathy and psychiatric symptoms had earlier AAO. Patients with cognitive
      impairment and extrapyramidal symptoms had higher CAG repeat length whereas
      presence of lower motor neuron signs was more common in patients with lower CAG
      repeat length. CONCLUSION: The lower strength of association between CAG repeat
      length and AAO in our cohort suggests the presence of additional factors
      underlying the variability in AAO. Both CAG repeat length and AAO were identified
      as significant determinants and predictors of non-ataxic symptoms.

PMID- 30196131
TI  - The plasticity of the corticospinal tract in children with obstetric brachial
      plexus palsy after Botulinum Toxin A treatment.
AB  - Botulinum neurotoxin A (BTX-A) intervention has long-term benefits for children
      with obstetric brachial plexus palsy (OBPP). Although cortical plasticity has
      been widely studied, plasticity in white matter has not received as much
      attention. Here, six children with OBPP underwent functional magnetic resonance
      imaging (fMRI) and diffusion tensor imaging (DTI) before and 6 months after BTX-A
      treatment. Surface electromyography (EMG) was recorded. The aim was to
      investigate changes in the corticospinal tract (CST) as an example longitudinal
      observation of white matter plasticity. Deterministic fiber tracking with a Fiber
      Assignment by Continuous Tracking algorithm was used to reconstruct the CST.
      Fiber tracts passing through a region of interest (ROI) in the posterior limb of
      the internal capsule and a target ROI in the upper-limb representation of M1
      (defined by task-related fMRI) were selected as the CST. Motor performances were
      improved while EMG showed no significant difference 6 months after the treatment.
      We observed a significant increase in mean fractional anisotropy and a
      significant decrease in fiber number after treatment. We analyzed the
      correlations between DTI metrics and clinical motor assessments. Although the
      correlation results were not statistically significant, they support the notion
      that BTX-A treatment causes white matter plasticity and has a positive long-term
      outcome. Peripheral deafferentation may lead to altered information flow,
      resulting in the positive adaptation of white matter. This study provides novel
      insight into cerebral plasticity following peripheral nerve regeneration and
      indicates that a combination of relatively non-invasive therapies can accelerate
      plasticity of sensorimotor circuits and promote functional recovery in OBPP.

PMID- 30196132
TI  - MicroRNAs to differentiate Parkinsonian disorders: Advances in biomarkers and
      therapeutics.
AB  - Parkinsonian disorders are a set of progressive neurodegenerative movement
      disorders characterized by rigidity, tremor, bradykinesia, postural instability
      and their distinction has significant implications in terms of management and
      prognosis. Parkinson's disease (PD) is the most common among them. Its clinical
      diagnosis is challenging and, it can be misdiagnosed in the early stages.
      Multiple system atrophy and progressive supranuclear palsy are the close
      mimickers in early stages, due to overlapping clinical features. MicroRNAs are a
      class of stable non-coding small RNA molecules implicated in post-transcriptional
      gene regulation. Current studies propose that miRNAs play an essential role in
      the pathobiology of multiple neurodegenerative disorders including Parkinsonism,
      and they seem to be one of the reasonably available methods to aid in the
      differential diagnosis between PD and related disorders. MicroRNA-based
      diagnostic biomarkers and therapeutics are a powerful tool to understand and
      explore the function of the pathogenic gene/s, their mechanism in the disease
      pathobiology, and to validate drug targets. In this review, we emphasize on the
      recent developments in the usage of miRNAs as diagnostic biomarkers to identify
      PD and to differentiate it from atypical parkinsonian conditions, their role in
      disease pathogenesis, and their possible utility in the therapy of these
      disorders.

PMID- 30196133
TI  - Estimating the uptake of brain imaging and 30-days stroke mortality in Nigeria: A
      meta-analysis of hospital-based studies.
AB  - PURPOSE: This study aims to estimate the computed tomography (CT) and Magnetic
      resonance imaging (MRI) uptake, stroke subtypes and 30-days case-fatality in
      Nigeria. METHODS: Stroke diagnosis and mortality data were identified from
      relevant databases. A random effect meta-analysis was conducted to obtain the
      pooled percentage uptake of CT/MRI, including 30-days case fatality and a meta
      regression-like epidemiological model was applied on all data points. FINDINGS: A
      total of 24 studies involving 5874 stroke patients conducted in predominantly
      tertiary referral hospitals met the inclusion criteria. The pooled CT/MRI uptake
      in the last seven years was 46.66% (95% CI = 15.35 to 77.98, 8 studies). There
      were significant variations in the prevalence of stroke subtypes. The pooled
      prevalence ischemic stroke was highest (55.32%, 95% CI 48.67 to 61.97, 16
      studies), followed by intracerebral haemorrhage (ICH) (32.69%, 95% CI 25.54 to
      39.83, 16 studies), subarachnoid haemorrhage (SAH) (3.76%, 95% CI 2.30 to 5.22,
      14 studies). In addition, the stroke of undetermined aetiology was found to be
      16.57% (95% CI, 7.44-25.70, 8 studies). Overall, the 24-h, one-week and 30-days
      case-fatality from stroke were 10.84% (95% CI, 4.48-17.20), 24.62% (95% CI, 17.20
      32.04) and 33.28% (95% CI, 27.80-38.77), respectively. There was a moderate
      negative correlation between prevalence of brain imaging uptake and ischaemic
      stroke, albeit not statistically significant (Spearman rho = 0.333, p-value =
      .412). CONCLUSION: Uptake of CT/MRI procedure for stroke is poor in Nigeria.
      Although poverty, inaccessibility and influence of major risk factors remain
      pronounced, scaling up of effective strategies for stroke prevention and
      management should be a major public health policy priority in Nigeria.

PMID- 30196134
TI  - Short Communication: Management of patients with extensive-stage small-cell lung
      cancer treated with radiotherapy: A survey of practice.
AB  - OBJECTIVES: The results of the randomized phase 3 CREST trial evaluating the use
      of thoracic radiotherapy for extensive-stage small-cell lung cancer (ES-SCLC)
      were published in the Lancet in 2015. The primary endpoint (10% overall survival
      difference at 1-year) was not achieved, but there was significant improvement in
      2-year overall survival (13% vs 3%; p = 0.004) and low toxicity rates, suggesting
      thoracic radiotherapy should be considered for ES-SCLC patients who respond to
      chemotherapy. Questions have been raised as to whether these results will lead to
      a change in practice. MATERIALS AND METHODS: We developed an electronic survey to
      determine the impact of the publication on clinical practice across some European
      countries. RESULTS AND CONCLUSION: We report the results of our survey, which
      suggest the CREST trial has changed practice, resulting in an increase in the use
      of thoracic radiotherapy amongst the surveyed centers from 25% to 85%.
      Furthermore the dose and fractionation schedule used in the trial has been widely
      adopted across Europe.

PMID- 30196135
TI  - Transient modification of lin28b expression - Permanent effects on zebrafish
      growth.
AB  - Recent genome-wide association studies and mouse models have identified LIN28B as
      a gene affecting several pubertal timing-related traits and vertebrate growth.
      However, the exact biological mechanisms underlying the associations remain
      unknown. We have explored the mechanisms linking LIN28B with growth regulation by
      combining human gene expression data with functional models. Specifically, we
      show that 1) pubertal timing-associated genetic variation correlates with LIN28B
      expression in the pituitary and hypothalamus, 2) downregulating lin28b in
      zebrafish embryos associates with aberrant development of kiss2-neurons, and 3)
      increasing lin28b expression transiently by synthetic mRNA injections during
      embryogenesis results in sustained enhancement of zebrafish growth. Unexpectedly,
      the mRNA injections resulted in advanced sexual maturation of female fish,
      suggesting that lin28b may influence pubertal timing through multiple
      developmental mechanisms. Overall, these results provide novel insight into
      LIN28B function in vertebrate growth regulation, emphasizing the importance of
      the gene and related genetic pathways for embryonic and juvenile development.

PMID- 30196136
TI  - Are the persistent effects of "gate control" stimulation on nociception a form of
      generalization of habituation that is endocannabinoid-dependent?
AB  - Repetitive activation of non-nociceptive afferents is known to attenuate
      nociceptive signaling. However, the functional details of how this modulatory
      process operates are not understood and this has been a barrier in using such
      stimuli to effectively treat chronic pain. The present study tests the hypothesis
      that the ability of repeated non-nociceptive stimuli to reduce nociception is a
      form of generalized habituation from the non-nociceptive stimulus-response
      pathway to the nociceptive pathway. Habituation training, using non-nociceptive
      mechanosensory stimuli, did reduce responses to nociceptive thermal stimulation.
      This generalization of habituation to nociceptive stimuli required
      endocannabinoid-mediated neuromodulation, although disrupting of endocannabinoid
      signaling did not affect "direct" habituation of to the non-nociceptive stimulus.
      Surprisingly, the reduced response to nociceptive stimuli following habituation
      training was very long-lasting (3-8 days). This long-term habituation required
      endocannabinoid signaling during the training/acquisition phase, but
      endocannabinoids were not required for post-training retention phase. The
      implications of these results are that applying principles of habituation
      learning could potentially improve anti-nociceptive therapies utilizing repeated
      non-nociceptive stimulation such as transcutaneous nerve stimulation (TENS),
      spinal cord stimulation (SCS), or electro-acupuncture.

PMID- 30196137
TI  - Microbial stress meeting: From systems to molecules and back.
AB  - The 4th Microbial Stress Meeting: from Systems to Moleculesand Back was held in
      April 2018 in Kinsale, Ireland. The meeting covered five main topics: 1. Stress
      at the systems and structural level; 2. Responses to osmotic and acid stress; 3.
      Stress responses in single cells; 4. Stress in host-pathogen interactions; and 5.
      Biotechnological optimisation of microorganisms through engineering and
      evolution, over three days. Almost 130 delegates, from 24 countries and both the
      industrial and academic sectors, attended the meeting, presenting 9 lectures, 28
      short talks and 52 posters. The meeting showcased the diverse and rapid
      advancements in microbial stress research, from the single cell level to mixed
      populations. In this report, a summary of the highlights from the meeting is
      presented.

PMID- 30196138
TI  - Burden of diabetes, hyperglycaemia in China from to 2016: Findings from the 1990
      to 2016, global burden of disease study.
AB  - AIMS: The prevalence of diabetes in China is among the highest in the world. For
      this reason, findings from the 2016 Global Burden of Disease (GBD) study were
      used to calculate the burden of hyperglycaemia and diabetes in China. METHODS:
      Following the general analytical strategy used in GBD 2016, diabetes prevalence
      and mortality were analyzed by age and gender. Trends in disability-adjusted life
      years (DALYs) due to diabetes were assessed in 33 province-level administrative
      units from 1990 to 2016, and similar data were provided for chronic kidney
      disease (CKD) related to diabetes and, as an overall summarizing measure, for
      hyperglycaemia expressed as high fasting plasma glucose (HFPG). RESULTS: From
      1990 to 2016, all-age prevalence of diabetes rose from 3.7% to 6.6%, and all-age
      diabetes and diabetes-related CKD mortality rates increased by 63.5% and 33.3%,
      respectively, with both rates increasing more rapidly in diabetes patients aged
      15-49 years than in any other age groups. In 2016, HFPG became China's sixth
      leading cause of DALYs, and the attributable DALYs burden was 1802.3/100,000
      population. Although the number of diabetes DALYs increased by 95% from 1990 to
      2016, age-standardized diabetes DALYs rates increased by only 2.3%. Also, from
      1990 to 2016, rates of age-standardized DALYs due to diabetes decreased in 14
      provinces, but increased in 19 provinces. High BMI Scores and diets low in whole
      grains, nuts and seeds were the most important risk factors for diabetes in 2016.
      CONCLUSION: Diabetes and hyperglycaemia constitute a huge health burden in China.
      The substantial increase in diabetes-related burden represents an ongoing
      challenge, given the rapidly ageing Chinese population. Thus, a targeted control
      and preventative strategy needs to be developed at risk factor level to reduce
      this burden.

PMID- 30196139
TI  - Effect of excipients on encapsulation and release of insulin from spray-dried
      solid lipid microparticles.
AB  - The study aimed at investigating the potential of spray drying method for
      encapsulation of protein drugs into solid lipid microparticles (MP) and
      evaluating effects of excipients on encapsulation and release of protein from MP.
      After transformation of model protein insulin to insulin-phospholipid complex, it
      was dissolved together with lipid excipients in organic solvent, which was spray
      dried to form solid lipid MP. Polymeric MP with D, L-lactic-co-glycolic acid
      (PLGA) were prepared similarly. Around 90% of insulin was encapsulated in
      glycerol monostearate MP and glycerol distearate MP, whereas the encapsulation
      efficiency was 60% and 35% for tristearate (TG18) MP and tribehenate (TG22) MP,
      respectively. The secondary structure of insulin in the spray-dried MP was
      substantially similar to that of the insulin control solution, suggesting that
      only minor alterations occurred during the spray drying process. Sustained
      release of insulin was observed from both TG18 MP and TG22 MP. The burst release
      of insulin from TG18 MP and TG22 MP was around 30% and 10%, respectively, which
      was significantly lower than that from PLGA MP (40%). In conclusion, spray drying
      a solution containing both lipids and protein-phospholipid complex is a promising
      method for encapsulating protein into solid lipid MP, which can be used for
      sustained delivery of protein drugs.

PMID- 30196140
TI  - Downscaling of the tableting process: Feasibility of miniaturized forced feeders
      on a high-speed rotary tablet press.
AB  - With the current transformation of the pharmaceutical industry towards continuous
      manufacturing, there is an inherent need to embrace this concept already during
      the early stages of drug formulation. Therefore, this research paper investigated
      the feasibility of using miniaturized forced feeders on a high-speed rotary
      tablet press with the intention of downscaling the tableting process. Forced
      feeders with a reduced volume (up to 46% compared to the conventional two
      compartment forced feeder) were designed by either sealing one compartment (i.e.
      R&D1) or lowering of the compartment height (i.e. R&D2). These feed frame designs
      were thoroughly analysed in combination with two paddle types over a wide range
      of process-settings (i.e. tableting speed, paddle speed, direction of paddle
      rotation, overfill-level). A poorly flowing model powder (i.e. MCC 101) was
      deliberately selected as challenging formulation. Empirical modelling of feed
      frame R&D1 revealed a positive impact on the die-filling variability when the
      radial curved cuboid paddles rotated in counterclockwise direction at high paddle
      speed. Moreover, a strong resemblance between the R&D2 feed frame and the
      conventional forced feeder was observed during multivariate data analysis,
      indicating that this miniaturized type could be used during downscaling studies
      of the conventional tableting process. The potential of this forced feeder was
      acknowledged by the similar trends in die-filling variability with respect to
      varying process settings, when a design-of-experiments (DOE) was performing
      including feed frame type as a qualitative factor. Overall, it was concluded that
      both types of miniaturized forced feeders can be used on a high-speed rotary
      tablet press when lower material consumption rates are desired while the R&D2
      feed frame bears the highest predictability regarding the die-filling uniformity
      in the conventional larger two-compartment forced feeder.

PMID- 30196141
TI  - Lipid-bilayer-coated nanogels allow for sustained release and enhanced
      internalization.
AB  - Nanoparticle drug delivery system improves the therapeutic efficacy of a drug;
      however, achieving sustained release from nanoparticles is challenging, owing to
      the increase of surface area and pronounced burst release. In this study, by
      incorporating an organogel of 12-hydroxystearic acid (12-HSA) into lipid
      bilayers, a gel-liposomal formulation was developed to sustain drug release over
      time. The lipid-bilayer-coated nanogels (LBCNs) with a particle size of
      approximately 200 nm and with a core-shell structure had an entrapment efficiency
      of up to 80% for paclitaxel. LBCNs could continually release both hydrophobic and
      water-soluble drugs over time. Interestingly, the incorporation of organogel
      enhanced the cellular uptake of liposomes significantly and, accordingly, enabled
      improved cytotoxicity of chemotherapy agent against the cancer cells. In
      conclusion, by formulating the organogel into the lipid bilayers, gel-liposomes
      were developed, allowing for sustained drug release, improved internalization and
      the resultant enhancement of cytotoxicity of chemotherapy agent to cancer cells.

PMID- 30196142
TI  - Loading studies of the anticancer drug camptothecin into dual stimuli-sensitive
      nanoparticles. Stability scrutiny.
AB  - In recent years, the preparation of valuable drug delivery systems (DDS) from
      self-assembled amphiphilic copolymers has attracted much attention since these
      nanomaterials provide new opportunities to solve problems such as the lack of
      solubility in water of lipophilic drugs, improve their bioavailability, prolong
      their circulation time and decrease the side effects associated with their
      administration. In the current study two types of biocompatible pH-responsive
      nanoparticles derived from poly(2-hydroxyethyl methacrylate) (pHEMA) have been
      used as drug nano-carriers, being one of them core cross-linked to circumvent
      their instability upon dilution in human fluids. The present paper deals with the
      optimization of the loading process of the labile, hydrophobic and highly active
      anticancer drug, Camptothecin (CPT) into the nanoparticles with regard to four
      independent variables: CPT/polymer ratio, sonication, temperature and loading
      time. Forty experiments were carried out and a Box-Behnken experimental design
      was used to evaluate the significance of the independent variables related to
      encapsulation efficiency and drug retention capacity. The enhanced drug loading
      and encapsulation efficiency values (58% and >92%, respectively) of CPT were
      achieved by the core cross-linked NPs in 2 h at 32  degrees C at CPT/polymer
      ratio 1.5:1 w/w and 14 min of sonication. The optimized CPT-loaded NPs were
      studied by dynamic light scattering and scanning electron microscopy, and an
      increase in size of the loaded-NP compared to the unloaded counterparts was
      found. Other twenty experiments were conducted to study the enability to retain
      CPT into the conjugates at different ionic strength values and times. The
      stability studies demonstrated that the core cross-linked nanocarriers displayed
      an excellent drug retention capacity (>90%) at 25  degrees C for 15 days in every
      ionic-strength environments whereas the non-cross-linked ones were more stable at
      physiological ionic strength. The optimized systems proved to be a major step
      forward to encapsulate and retain CPT in the NP nuclei, what makes them ideal
      devices to control the delivery of CPT upon the triggered acidic conditions of
      solid tumors.

PMID- 30196143
TI  - General health perception, depression and quality of life in geriatric
      grandmothers providing care for grandchildren.
AB  - AIM/BACKGROUND: To investigate levels of depression, quality of life, general
      health perception, and factors affecting these in grandmothers providing care for
      their grandchildren. MATERIAL/METHOD: One hundred two family physicians from four
      cities (Samsun, Amasya, Canakkale, and Izmir) in Turkey investigated 2859 women
      older than 65 years on their patient lists. Of these, 282 (9.8%) had spent at
      least 50 h caring for their grandchildren in the previous three months, and these
      were selected as the study group, while the remaining 2563 (89.6%) were enrolled
      as the control group. After all participants' demographic variables had been
      investigated, they completed the Beck Depression Inventory (BDI), Self-Function
      12 (Mental and physical component score) (SF-12), and the Visual Analog Scale of
      EQ-5D (VAS). The participants in the study group also completed a questionnaire
      investigating features of their grandchild care. RESULTS: The study group (with
      the exception of custodial grandmothers) scored better on the SF-12 (PSC = 50.60
      +/- 6.96 vs 48.24 +/- 8.12), (MCS = 49.70 +/- 7.77 vs 45.48 +/- 7.61), VAS (60.44
      +/- 23.5 vs 54.16 +/- 19.5), and BDI (13.97 +/- 0.3 vs 19.49 +/- 0.2) compared to
      the control group (p < 0.0001 for all). Age, monthly income, mean length of
      education, duration of care, mean hours spent caregiving per week, being a
      custodial grandmother, presence of more than one chronic disease, and caring for
      more than one grandchild at a time were identified as factors affecting SF-12,
      VAS and BID in the study group. CONCLUSION: Grandchild care positively affected
      the grandmothers' quality of life, depression levels, and general health
      perception, with the exception of custodial grandmothers.

PMID- 30196144
TI  - Different impacts of dementia on two-year mortality after osteosynthesis and
      hemiarthroplasty in treating geriatric hip fractures.
AB  - BACKGROUND: Geriatric hip fractures are mostly managed by internal fixation (IF)
      or hemiarthroplasty (HA). Survivorship of dementia patients following these
      surgeries has not been extensively compared in literature. By analysis of
      nationwide database, this study aimed to investigate the impact of dementia on
      two-year mortality after IF and HA in treating geriatric hip fractures. METHOD:
      From retrospective review of Taiwan's National Health Insurance Research
      Database, we enrolled 153,623 subjects aged 65 years and older with
      hospitalization for first hip fracture operated by IF (93,029 cases) or HA
      (60,594 cases) between 2000 and 2011. Postoperative mortality was compared
      between subjects with and without dementia after adjustments of age, gender,
      Charlson comorbidity index and hospital level. RESULTS: The prevalence of
      dementia was 5.24% in the IF and 5.29% in the HA group. In the IF group, dementia
      increased adjusted hazard ratio of one-year (1.06, 95%CI:1.00-1.13) and two-year
      mortality (1.10, 95%CI:1.05-1.16). However, short and long-term mortality
      following HA was not significantly impacted by dementia (in-hospital OR:0.79,
      95%CI:0.60-1.03; three-month HR:0.99, 95%CI:0.87-1.12; one-year HR:1.01,
      95%CI:0.93-1.10; two-year HR:1.03, 95%CI:0.96-1.09). In a subgroup of dementia
      patients, mortality following IF was 15% higher than HA in one (p = 0.004) and
      two years (p < 0.001). The negative prognostic factors included female (HR:1.10;
      95%CI:1.03-1.18) and aging 65-84 years (HR:1.15; 95%CI:1.00-1.32). CONCLUSION:
      Dementia increased one and two-year mortality following geriatric hip fracture
      treated by IF, rather than HA. Dementia patients undergoing HA, especially female
      or 65-84 years old, sustained better one and two-year survival than those
      receiving IF.

PMID- 30196145
TI  - Neuronal Growth Factor regulates Brain Specific Kinase 1 expression by inhibiting
      promoter methylation and promoting Sp1 recruitment.
AB  - Brain specific kinases (BRSKs) are serine/threonine kinases, preferentially
      expressed in the brain after Embryonic Day 12. Although BRSKs are crucial
      neuronal development factors and regulation of their enzymatic activity has been
      widely explored, little is known of their transcriptional regulation. In this
      work, we show that Neuronal Growth Factor (NGF) increased the expression of Brsk1
      in PC12 cells. Furthermore, during neuronal differentiation, Brsk1 mRNA increased
      through a MAPK-dependent Sp1 activation. To gain further insight into this
      regulation, we analyzed the transcriptional activity of the Brsk1 promoter in
      PC12 cells treated with NGF. Initially, we defined the minimal promoter region (
      342 to +125 bp) responsive to NGF treatment. This region had multiple Sp1 binding
      sites, one of which was within a CpG island. In vitro binding assays showed that
      NGF-induced differentiation increased Sp1 binding to this site and that DNA
      methylation inhibited Sp1 binding. In vitro methylation of the Brsk1 promoter
      reduced its transcriptional activity and impaired the NGF effect. To evaluate the
      participation of DNA methyltransferases in Brsk1 gene regulation, the 5'Aza-dC
      inhibitor was used. 5'Aza-dC acted synergistically with NGF to promote Brsk1
      promoter activity. Accordingly, DNMT3B overexpression abolished the response of
      the Brsk1 promoter to NGF. Surprisingly, we found Dnmt3b to be a direct target of
      NGF regulation, via the MAPK pathway. In conclusion, our results provide evidence
      of a novel mechanism of Brsk1 transcriptional regulation changing the promoter's
      methylation status, which was incited by the NGF-induced neuronal differentiation
      process.

PMID- 30196146
TI  - Effect of Angelica polysaccharide on brain senescence of Nestin-GFP mice induced
      by D-galactose.
AB  - The incidence of neurodegenerative diseases is severely increasing with the
      aging. It has been proposed that NSCs (neural stem cells) help to control aging,
      but the mechanisms responsible remain unclear. Angelica polysaccharide is an
      active ingredient of Angelica sinensis in traditional Chinese medicine, which
      possesses versatile pharmacological activities including anti-oxidative and anti
      aging effects. In this study, D-gal (D-galactose) was used to construct an aging
      model of Nestin-GFP transgenic mice brain tissues and NSCs. Mouse model was
      subcutaneously injected with D-gal, as we observed that mice consistently
      displayed acceleration of aging-like behavior change, energy metabolism
      decreased, the expression of aging-related genes was up-regulated. Conversely,
      aging retardation was achieved in Nestin-GFP mice Induced by D-gal that was
      locally injected with ASP (Angelica polysaccharide). Mechanistically, we isolated
      and cultured NSCs in vitro. ASP protected NSCs by increasing the cell
      proliferation; decreasing the number of SA-beta-gal stained neurons; increasing
      the activity of SOD(superoxide dismutase) and T-AOC(total antioxidant capacity),
      decreasing the content of MDA(malondialdehyde); decreasing the levels of IL-1b,IL
      6,TNF-a and ROS; and down-regulated the expression of cellular senescence
      associated genes p53, p21 in the aging NSCs. In conclusion, ASP can delay aging
      speed by protecting NSCs and promote neurogenesis by enhancing the antioxidant
      and anti-inflammatory capacity, up-regulation of p53/p21 signaling pathway. As to
      provide theoretical basis for treatment for brain aging related diseases, add new
      scientific connotation for "qi and blood theory" and "supplement blood and delay
      aging" of Traditional Chinese Medicine.

PMID- 30196147
TI  - Knockdown the P2X3 receptor in the stellate ganglia of rats relieved the diabetic
      cardiac autonomic neuropathy.
AB  - Diabetic cardiac autonomic neuropathy (DCAN) is a common and serious complication
      of diabetes mellitus (DM), is manifested by nerve fiber injury in the sympathetic
      and parasympathetic nerve of the autonomic nervous system, and causes
      hypertension, cardiac arrhythmias, silent myocardial infarction, and sudden
      death. Our previous study observed that P2X3 receptor in superior cervical
      ganglia in rat was associated with sympathetic neuropathy caused by myocardial
      ischemia. However, whether the P2X3 receptor is involved in the diabetic cardiac
      autonomic neuropathy and the underlying mechanisms remain unclear. The aim of
      this research was explored the effect of P2X3 short hairpin RNA (shRNA) on
      information transmission of sympathetic nerve induced by DCAN. Sprague-Dawley
      (SD) male rats were randomly divided into four groups: Control, DM, DM treated
      with P2X3 shRNA and DM treated with scramble shRNA. Blood pressure, heart rate
      and heart rate variability were measured in each group. The expression of P2X3 in
      stellate ganglion (SG) was detected by immunohistochemistry, western blotting and
      QPCR. Results showed that P2X3 shRNA alleviated blood pressure and heart rate,
      improved heart rate variability, decreased the up-regulated expression levels of
      P2X3, interleukin-1beta and tumor necrosis factor alpha in stellate ganglion (SG)
      of diabetic rats. P2X3 shRNA also reduced the incremental concentration of serum
      epinephrine and the phosphorylation level of extracellular regulated protein
      kinases1/2 in diabetic rats. These results indicated that P2X3 shRNA could
      decrease sympathetic activity via inhibiting P2X3 receptor in the SG to alleviate
      DCAN.

PMID- 30196148
TI  - Forecasting and foreclosing futures: The temporal dissonance of advance care
      directives.
AB  - Advance care directives situate persons as rational and self-determining actors
      who can make anticipatory plans about their futures. This paper critically
      examines how people interpret individual and future-oriented approaches to
      medical decision-making with limited access to information and knowledge, and
      reduced opportunities to prepare and document their care preferences. Based on
      ethnographic research with Asian migrant families living in Adelaide, South
      Australia (August 2015-July 2018), it reveals a discord between planning for a
      finite future and the contingencies and continuities of social life. It unsettles
      the detached reasoning that is privileged in end-of-life decision-making and
      reveals limitations to "do-it-yourself" approaches to advance care directives
      which, it will be argued, not only forecasts potential futures but also
      forecloses them. Taking Derrida's critique of death and decision-making as a
      point of departure, it develops the concept of temporal dissonance as a
      theoretical framework to articulate the tensions that are constituted in advance
      care directives. The paper suggests that attention to temporal incongruities may
      help to shed light on the many complex interpretations of advance care directives
      and the difficulties of promoting them in diverse contexts.

PMID- 30196149
TI  - Measuring income for catastrophic cost estimates: Limitations and policy
      implications of current approaches.
AB  - There is increasing global policy interest in estimating catastrophic costs
      incurred by households because of ill health, and growing need for information on
      disease-specific household cost data. There are several methodological approaches
      used to estimate income and no current consensus on the best method for
      estimating income in the context of a survey at the health facility. We compared
      six different approaches to estimate catastrophic cost among patients attending a
      health facility in South Africa. We used patient cost and income data collected
      June 2014-March 2015 from 66 participants enrolled in a clinical trial in South
      Africa (TB FastTrack) to explore the variation arising from different income
      estimation approaches and compared the number of households encountering
      catastrophic costs derived for each approach. The total proportion of households
      encountering catastrophic costs varied from 0% to 36%, depending on the
      estimation method. Self-reported mean annual income was significantly lower than
      permanent income estimated using an asset linking approach, or income estimated
      using the national average. A disproportionate number of participants adopting
      certain coping strategies, including selling assets and taking loans, were unable
      to provide self-reported income data. We conclude that the rapid methods for
      estimating income among patients attending a health facility are currently
      inconsistent. Further research on methods for measuring income, comparing the
      current recommended methods to 'gold standard' methods in different settings,
      should be done to identify the most appropriate measurement method.

PMID- 30196150
TI  - Confidence: Fundamental to midwives providing labour care in freestanding
      midwifery-led units.
AB  - : The aim of this study was to reveal what enables, safeguards and sustains
      midwives to provide labour care in freestanding midwifery-led units. DESIGN: A
      hermeneutic phenomenological study was undertaken in the Auckland region of New
      Zealand. In-depth interviews were conducted with 14 participants: 11 midwives who
      provide care in freestanding midwifery-led units and three obstetricians who
      provide antenatal consultations on site in midwifery-led units. MAIN FINDINGS:
      Confidence is necessary to provide intrapartum care in freestanding midwifery
      units. This confidence is cultivated by working in the community or freestanding
      unit and believing this unit is an appropriate space for healthy women to labour
      and birth. Normal labour and birth are commonplace in this space which in turn
      reinforces midwives' confidence. Maintaining confidence for midwives to work in
      these units requires trusting relationships in the midwifery team. Further, there
      needs to be mutually respectful relationships with obstetric colleagues. Midwives
      who have lesser experience, or experience in obstetric unit only, may need
      support to step into the role of providing labour care in freestanding midwifery
      units. When the midwife feels supported, when s/he witnesses women and families
      experiencing their normal birth, one's resolve to practising in this manner is
      strengthened. The midwife holds confidence. KEY CONCLUSIONS AND IMPLICATIONS FOR
      PRACTICE: Confidence required to provide labour care in a midwifery-led unit is
      cultivated through immersion in these units.

PMID- 30196151
TI  - A new temperature-dependent strategy to modulate the epidermal growth factor
      receptor.
AB  - The dynamic manipulation of kinases remains a major obstacle to unraveling cell
      signaling networks responsible for the activation of biological systems. For
      example, epidermal growth factor (EGF) stimulates the epidermal growth factor
      receptor (EGFR/ErbB1); however, EGF also recruits other kinases (HER2/ErbB2)
      involved with various signaling pathways. To better study EGFR we report a new
      strategy to selectively activate receptor tyrosine kinases fused to elastin-like
      polypeptides (ELPs), which can be visualized inside mammalian cells using fixed
      and live-cell fluorescence microscopy. ELPs are high molecular weight
      polypeptides that phase separate abruptly upon heating. When an EGFR-ELP fusion
      is heated, it clusters, initiates receptor internalization, phosphorylates,
      initiates downstream kinase signaling, and undergoes retrograde transport towards
      the cell body. Unlike other strategies to block EGFR (small molecule inhibitors,
      RNAi, or transcriptional regulators), EGFR-ELP clustering can be specifically
      switched on or off within minutes. Live-cell imaging suggests that EGFR-ELPs
      assemble in most cells with only a 3  degrees C increase in temperature. This
      strategy was found reversible and able to dynamically control the downstream
      phosphorylation/activation of the ERK1/2 pathway. For the first time, this
      strategy enables the rational engineering of specific temperature-sensitive
      receptors that may have broad applications in the study and manipulation of
      biological processes.

PMID- 30196152
TI  - Nitrogen and sulfur co-doped graphene quantum dots for the highly sensitive and
      selective detection of mercury ion in living cells.
AB  - In this work, a novel nitrogen and sulfur co-doped graphene quantum dots
      (N,S/GQDs) were synthesized by a simple and green pyrolysis method with citric
      acid as carbon source, d-penicillamine as doped molecule. The obtained N,S/GQDs
      shows good water solubility, low cytotoxicity and high quantum yield of 56.4%.
      The doping of N and S can efficient promoted the coordination between the
      residual group of N,S/GQDs and Hg2+, thus, the fluorescence of N,S/GQDs can be
      dramatically and selectively quenched by Hg2+. Under the optimum conditions, the
      quenching effect of Hg2+ to N,S/GQDs was lined with its concentrations in the
      range of 0.9 to 30 nM with a detection limit of 0.69 nM. 100 fold of common
      metals had no influence for the determination of Hg2+. When Hela cells were
      incubated into the N,S/GQDs solutions for 2 h, more than 85% Cells still kept
      living even at a high concentration of 400 MUg/mL suggesting the good
      biocompatibility and low toxicity of the obtained N,S/GQDs. Besides this, the
      N,S/GQDs also showed good cell permeability and could enter into the cell and
      showed bright blue light. Thus, they were successfully applied as a powerful
      fluorescent nano-sensor for imaging detection of mercury ions in the living
      cells.

PMID- 30196153
TI  - Raman Optical Activity and Raman spectroscopy of carbohydrates in solution.
AB  - This comprehensive study on selected 14 carbohydrates in water solution is an
      extension of previously published one focused only on solid state analysis. Here,
      Raman spectroscopy was used as a dedicated method for analysis of carbohydrates
      in solution, both using a normal effect (RS) and its chiral analogue: Raman
      Optical Activity spectroscopy (ROA). The compounds were selected as biologically
      important and representative of all groups: monosaccharides, disaccharides,
      trisaccharides, cyclodextrines and polysaccharides. RS and ROA spectra are
      presented together with an expanded discussion on various structures and
      conformations of studied carbohydrates in the solution taking into account
      particular regions, i.e. (1) low wavenumber region (250-600 cm-1), (2) anomeric
      region (600-950 cm-1), (3) fingerprint region (950-1200 cm-1) and (4) CH2and COH
      deformations region (1200-1500 cm-1). So, the following information can be
      obtained about: (1) the absolute configuration of the anomeric centre; (2) the
      configuration of the anomeric centre and the orientation of the anomeric hydroxyl
      group; (3) the ring structures and the relative orientation of substituents and
      (4) the conformation of the exocyclic CH2OH (4), respectively. Raman spectroscopy
      and Raman Optical Activity were shown as unique tools to study complex structures
      of carbohydrates.

PMID- 30196154
TI  - Lipid-protein interactions in mitochondrial membranes from bivalve mollusks:
      molecular strategies in different species.
AB  - The mitochondrial F1FO-ATPase, the key enzyme in cell bioenergetics, apparently
      works in the same way in mollusks and in mammals. We previously pointed out a
      raft-like arrangement in mussel gill mitochondrial membranes, which apparently
      distinguishes bivalve mollusks from mammals. To explore the relationship between
      the microenvironmental features and the enzyme activity, the physico-chemical
      features of mitochondrial membranes and the F1FO-ATPase activity temperature
      dependence are here explored in the Manila clam (Ruditapes philippinarum).
      Similarly to the mussel, clam gill mitochondrial membrane lipids exhibit a high
      sterol content (42 mg/g protein), mainly due to phytosterols (cholesterol only
      attains 42% of total sterols), and abundant polyunsaturated fatty acids (PUFA)
      (70% of total fatty acids), especially of the n-3 family. However, the F1FO
      ATPase activation energies above and below the break in the Arrhenius plot (22.1 
      degrees C) are lower than in mussel and mammalian mitochondria. Laurdan
      fluorescence spectroscopy analyses carried out at 10  degrees C, 20  degrees C
      and 30  degrees C on mitochondrial membranes and on lipid vesicles obtained from
      total lipid extracts of mitochondria, indicate a physical state without
      coexisting domains. This mitochondrial membrane constitution, allowed by lipid
      lipid and lipidprotein interactions and involving PUFA-rich phospholipids,
      phytosterols (much more diversified in clams than in mussels) and proteins,
      enables the maintenance of a homogeneous physical state in the range 10-30 
      degrees C. Consistently, this molecular interaction network would somehow extend
      the temperature range of the F1FO-ATPase activity and may contribute to clam
      resilience to temperature changes.

PMID- 30196155
TI  - Range of Normal Liver Stiffness and Factors Associated With Increased Stiffness
      Measurements in Apparently Healthy Individuals.
AB  - BACKGROUND & AIMS: Transient elastography (TE) is a noninvasive technique used to
      measure liver stiffness to estimate the severity of fibrosis. The range of liver
      stiffness measurements (LSMs) in healthy individuals is unclear. We performed a
      systematic review to determine the range of LSMs, examined by TE, in healthy
      individuals and individuals who are susceptible to fibrosis. METHODS: We
      collected data from 16,082 individuals, in 26 cohorts, identified from systematic
      searches of Embase, Ovid MEDLINE, Cochrane Central Register of Controlled Trials,
      and Cochrane Database of Systematic Reviews for studies of liver stiffness
      measurements. Studies analyzed included apparently healthy adults (normal levels
      of liver enzymes, low-risk alcohol use patterns, and negative for markers of
      viral hepatitis). The presence of diabetes, hypertension, dyslipidemia, or
      steatosis, based on ultrasound examination, was known for most participants. We
      performed a meta-analysis of data from individual participants. The cohort was
      divided into 4 groups; participants with a body mass index <30 kg/m2 were
      examined with the medium probe and those with a body mass index >=30 kg/m2 were
      examined with the extra-large probe. Linear regression models were conducted
      after adjusting for potential confounding factors of LSMs. We performed several
      sensitivity analyses. RESULTS: We established LSM ranges for healthy individuals
      measured with both probes-these did not change significantly in sensitivity
      analyses of individuals with platelets >=150,000/mm3 and levels of alanine
      aminotransferase <=33 IU/L in men or <=25 IU/L in women. In multivariate
      analysis, factors that modified LSMs with statistical significance included
      diabetes, dyslipidemia, waist circumference, level of aspartate aminotransferase,
      and systolic blood pressure at examination time. Significant increases in LSMs
      were associated with the metabolic syndrome in individuals examined by either
      probe. Diabetes in obese individuals increased the risk of LSMs in the range
      associated with advanced fibrosis. CONCLUSIONS: In a systematic review and meta
      analysis of data from individual patients, we established a comprehensive set of
      LSM ranges, measured by TE in large cohorts of healthy individuals and persons
      susceptible to hepatic fibrosis. Regression analyses identified factors
      associated with LSMs made by TE with the medium and extra-large probes.

PMID- 30196156
TI  - Emerging Role of the Gut Microbiome in Nonalcoholic Fatty Liver Disease: From
      Composition to Function.
AB  - The gut microbiome, a diverse microbial community in the gastrointestinal tract,
      plays a pivotal role in the maintenance of health. The gut microbiome metabolizes
      dietary and host-derived molecules to produce bioactive metabolites, which have a
      wide array of effects on host metabolism and immunity. 'Dysbiosis' of the gut
      microbiome, commonly considered as perturbation of microbiome diversity and
      composition, has been associated with intestinal and extra-intestinal diseases,
      including nonalcoholic fatty liver disease (NAFLD). A number of endogenous and
      exogenous factors, such as nutritional intake and xenobiotic exposure, can alter
      the gut microbiome. We will review the evolving methods for studying the gut
      microbiome and how these profiling techniques have been utilized to further our
      understanding of the gut microbial community composition and functional potential
      in the clinical spectrum of NAFLD. We will highlight microbiome-host interactions
      that may contribute to the pathogenesis of NAFLD, with a primary focus on
      mechanisms related to the metabolic output of the gut microbiome. Finally, we
      will discuss potential therapeutic implications of the gut microbiome in NAFLD.

PMID- 30196157
TI  - Low Prevalence of Suspected Barrett's Esophagus in Patients with Gastroesophageal
      Reflux Disease Without Alarm Symptoms.
AB  - BACKGROUND & AIMS: Esophagogastroduodenoscopy (EGD) is frequently used to
      evaluate gastroesophageal reflux disease (GERD) without alarm symptoms, although
      the benefits are not clear. We aimed to determine the prevalence of uncomplicated
      GERD as an indication for EGD, the demographic characteristics of these patients,
      and the endoscopic outcomes of these procedures. METHODS: We collected endoscopy
      data from a large national database of 543,103 EGDs performed at 82 sites from
      2003 through 2014. We identified patients with GERD without alarm symptoms
      (dysphagia, bleeding, vomiting, or weight loss). Endpoints included the
      prevalence of endoscopically suspected Barrett's esophagus (sBE) and suspected
      long-segment BE (sLSBE), defined as >=3 cm. RESULTS: We found that 73,535 EGDs
      (13.5%) were performed for a primary indication of GERD without alarm symptoms:
      only 4122 patients (5.6%) had sBE, and of these, 24.2% had sLSBE. Significant
      risk factors for sBE and sLSBE included male sex, age, and white race. Other
      findings included peptic ulcers in 1337 patients (1.8%) and suspected tumors (47
      esophageal, 42 gastric, 13 duodenal tumors, 2 others) in 101 patients.
      CONCLUSIONS: In an analysis of a large cohort of patients undergoing EGD,
      uncomplicated GERD accounted for almost 14% of EGDs; within this population, only
      23.6% were white men older than 50 years, who have an increased risk of BE and
      esophageal adenocarcinoma. The prevalence of sBE is lower than in prior time
      periods-this raises questions about the utility of EGD to detect BE in patients
      with uncomplicated GERD. Guidelines for management of uncomplicated GERD should
      account for these observations.

PMID- 30196158
TI  - Rectovesical Fistula Presenting as Diarrhea.

PMID- 30196159
TI  - Late-Presenting Duodenal Web.

PMID- 30196160
TI  - Influence of Early Life, Diet, and the Environment on the Microbiome.
AB  - Advances in sequencing technology and bioinformatics have greatly enhanced our
      ability to understand the human microbiome. Over the last decade, a growing body
      of literature has linked nutrition and the environment to the microbiome and is
      now thought to be an important contributor to overall health. This paper reviews
      the literature from the past 10 years to highlight the influence of environmental
      factors such as diet, early life adversity and stress in shaping and modifying
      our microbiome towards health and disease. The review shows that many factors
      such as the mode of delivery, breast milk, stress, diet and medications can
      greatly influence the development of our gut microbiome and potentially make us
      more prone to certain diseases. By incorporating environmental factors into
      models that study the microbiome in the setting of health and disease, may
      provide a better understanding of disease and potentially new areas of treatment.
      To highlight this, we will additionally explore the role of the environment and
      the microbiome in the development of obesity and functional bowel disorders.

PMID- 30196161
TI  - Confirmatory Visualization of an Aorto-enteric Fistula With
      Esophagogastroduodenoscopy.

PMID- 30196162
TI  - Brunner's Gland Hamartoma Arising From the Pyloric Ring.

PMID- 30196163
TI  - The Microbiome in Inflammatory Bowel Disease: From Prevailing Clinical Evidence
      to Future Possibilities.
AB  - ???.

PMID- 30196164
TI  - Switching Between Biologics and Biosimilars in Inflammatory Bowel Disease.

PMID- 30196165
TI  - Everted Liver Secondary to Diaphragmatic Eventration: A Very Rare Presentation.

PMID- 30196166
TI  - Agreement and reliability of the velocity time integral method and the method of
      disks to determine stroke volume in preterm infants.

PMID- 30196167
TI  - Scalar diffusion-MRI measures invariant to acquisition parameters: A first step
      towards imaging biomarkers.
AB  - An imaging biomarker is a biologic feature in an image that is relevant to a
      patient's diagnosis or prognosis. In order to qualify as a biomarker, a measure
      must be robust and reproducible. However, the usual scalar measures derived from
      diffusion tensor imaging are known to be highly dependent on the variation of the
      acquisition parameters, which prevents their possible use as biomarkers. In this
      work, we propose a new set of quantitative measures based on diffusion magnetic
      resonance imaging from single-shell acquisitions that are designed to be robust
      to the variations of several acquisition parameters (number of gradient
      directions, b-value and SNR) while keeping a high discrimination power on
      differences in the diffusion characteristics of the tissue. These new scalar
      measures are analytically obtained from a generic diffusion function that does
      not require the calculation of a diffusion tensor. This way, on one hand, we
      avoid the use of a specific diffusion model and, on the other hand, we make
      easier the statistical characterization of the measures. Accordingly, the
      analysis of the measures bias is carried out and it is used to minimize their
      dependency with respect to the acquisition noise for different SNRs. The
      robustness and discrimination power of the measures are tested for different
      number of gradients, b-values and SNRs using a realistic phantom and three real
      datasets: (1) 13 control subjects and different acquisition parameters; (2) a
      public data set from a single subject acquired using multiple shells and (3) 32
      schizophrenia patients and 32 age and sex-matched healthy controls with a varying
      number of gradient directions. The proposed quantitative measures exhibit low
      variability to the changes of the acquisition parameters, while at the same time
      they preserve a discrimination power that is able to detect significant changes
      in the anisotropy of the diffusion.

PMID- 30196168
TI  - Contrast Media-Induced Nephropathy in Patients with Unruptured Cerebral Aneurysm
      After Coiling Endovascular Treatment.
AB  - BACKGROUND: The endovascular coiling procedure to treat cerebral aneurysms using
      contrast media has become more popular. However, studies of the incidence of, and
      risk factors for, contrast media-induced nephropathy (CIN) after coiling
      procedures have been limited. Thus, we evaluated the incidence and risk factors
      for CIN in patients who had undergone cerebral aneurysmal coiling procedures.
      METHODS: We retrospectively reviewed the electric medical records of 380 patients
      who had undergone cerebral aneurysmal coiling treatment under general anesthesia.
      CIN was defined as an absolute increase in serum creatinine (>=0.5 mg/dL) or a
      relative increase (>=25%) in the baseline serum creatinine value at 48-72 hours
      after exposure to a contrast agent. RESULTS: Elective cerebral aneurysmal coiling
      procedures were performed in 230 patients. Of the 230 patients, CIN developed in
      13 (5.6%). The presence of diabetes mellitus (30.8% vs. 9.7%; P = 0.040) and
      patient age >75 years (30.8% vs. 6.5%; P = 0.012) were risk factors for CIN.
      CONCLUSIONS: Our study has demonstrated that the incidence of CIN in patients
      undergoing elective cerebral aneurysmal coiling procedures is ~6.0%. We also
      identified underlying diabetes mellitus and advanced age (>=75 years) as
      potential risk factors.

PMID- 30196169
TI  - Novel Indirect Revascularization Technique with Preservation of Temporal Muscle
      Function for Moyamoya Disease Encephalo-Duro-Fascio-Arterio-Pericranial
      Synangiosis: A Case Series and Technical Note.
AB  - BACKGROUND: Direct and/or indirect bypass surgery is the established approach for
      preventing stroke in patients with moyamoya disease. However, conventional
      indirect revascularization, including encephalo-myo-synangiosis, has some
      disadvantages associated with the mass effect of the temporal muscle under the
      bone flap and postsurgical depression in the temporal region. We devised a novel
      indirect revascularization method, using only the temporal fascia, to address the
      aforementioned disadvantages. METHODS: A skin incision was performed along the
      superficial temporal artery. The temporal fascia was cut such that the base of
      the fascia flap was on the posterior side. The fascia and temporal muscles were
      dissected separately. After turning over the fascia, the muscle was cut such that
      the base of the muscle flap was on the anterior side. Craniotomy, direct bypass,
      and encephalo-duro-synangiosis were performed conventionally. Only the temporal
      fascia was used for indirect revascularization and duraplasty. The muscle was
      replaced in the anatomically correct position after replacing the bone flap.
      RESULTS: We performed the aforementioned surgery on 18 (13 women and 5 men)
      consecutive patients (21 cerebral hemispheres) enrolled between 2012 and 2016.
      The average age was 28.7 years. The mean follow-up period was 31.6 months. In 17
      patients (94%), the symptoms and cerebral blood flow improved. Digital
      subtraction angiography showed satisfactory angiogenesis from the temporal
      fascia. Depression in the temporal region and atrophy of the temporal muscle were
      negligible. CONCLUSIONS: This surgical technique provides good clinical and
      cosmetic outcomes. It may also be one of the good surgical treatments available
      for symptomatic moyamoya disease.

PMID- 30196170
TI  - Is Extended Lesionectomy Needed for Patients with Cerebral Cavernous
      Malformations Presenting with Epilepsy? A Meta-Analysis.
AB  - OBJECTIVE: To determine whether extended lesionectomy is needed for patients with
      cerebral cavernous malformations presenting with epilepsy as compared with
      lesionectomy. METHODS: A literature search of PubMed, Embase, Web of Science,
      Clinical Trials and Cochrane Central Register of Controlled Trials was performed
      for pertinent English-language studies from 1967 to 2017. Eligible studies were
      selected according to uniform inclusion and exclusion criteria. RESULTS: Seven
      studies including 245 patients (107 receiving extended lesionectomy, 138
      receiving lesionectomy) were selected. Meta-analysis and subgroup analyses were
      conducted to compare extended lesionectomy with lesionectomy. Pooled analysis
      demonstrated that seizure outcome was not statistically significantly improved in
      patients who underwent extended lesionectomy compared with lesionectomy (odds
      ratio = 0.77; 95% confidence interval, 0.39-1.51; P = 0.44; I2 = 15%).
      CONCLUSIONS: Extended lesionectomy does not contribute to better seizure control
      for patients with cerebral cavernous malformations with epilepsy. Resection of
      the lesion and surrounding hemosiderin is sufficient for patients with cerebral
      cavernous malformations presenting with epilepsy.

PMID- 30196171
TI  - Vaccine-Based Immunotherapeutics for the Treatment of Glioblastoma: Advances,
      Challenges, and Future Perspectives.
AB  - Glioblastoma is a highly aggressive neoplasm with an extremely poor prognosis.
      Despite maximal gross resection and chemoradiotherapy, these grade IV
      astrocytomas consistently recur. Glioblastoma cells exhibit numerous pathogenic
      mechanisms to decrease tumor immunogenicity while promoting gliomagenesis, which
      manifests clinically as a median survival of less than 2 years and few long-term
      survivors. Recent clinical trials of vaccine-based immunotherapeutics against
      glioblastoma have demonstrated encouraging results in prolonging progression-free
      survival and overall survival. Several vaccine-based treatments have been
      trialed, such as peptide and heat-shock proteins, dendritic cell-based vaccines,
      and viral-based immunotherapy. In this literature review, we discuss the
      immunobiology of glioblastoma, significant current and completed vaccine-based
      immunotherapy clinical trials, and broad clinical challenges and future
      directions of glioblastoma vaccine-based immunotherapeutics.

PMID- 30196172
TI  - The Effect of Preoperative Direct Ligation of Ethmoidal Arteries on the
      Perioperative Outcomes of Large Anterior Skull Base Meningiomas Surgery: A
      Clinical Study.
AB  - BACKGROUND: Anterior skull base meningiomas often grow to a large size (>=4 cm)
      before detection. Their blood supply is mostly provided by the anterior and
      posterior ethmoidal arteries. Because of their vascularity, intraoperative
      bleeding can be a challenging prospect that increases the risk of perioperative
      complications. Preoperative ethmoidal arteries ligation has been used to aid in
      limiting blood loss. Our objective was to assess the effect of preoperative
      arterial ligation on the perioperative course of large (>=4 cm) to giant (>=6 cm)
      anterior skull base meningiomas. METHODS: We retrospectively searched our
      database for large anterior skull base meningiomas (>=4 cm). We analyzed
      differences in intraoperative blood loss, operative time, intraoperative
      transfusion, and hematologic parameters between patients who did not undergo
      preoperative ethmoidal arteries ligation (Group 1) and those who did (Group 2).
      RESULTS: Average estimated blood loss (EBL) was 825 mL (Group 1) versus 350 mL
      (Group 2) (P = 0.42), decrease in hemoglobin was 4 g/dL versus 3.2 g/dL (P =
      0.53), decrease in hematocrit was 12.4% versus 9.6% (P = 0.64), and average
      operative time was 656 minutes versus 598 minutes (P = 0.58). EBL per volume
      yielded a ratio of 10.6 mL/cm3 versus 4.1 mL/cm3 (P = 0.06). CONCLUSIONS:
      Ethmoidal arteries ligation may have a benefit in large-to-giant anterior skull
      base meningiomas surgery. Our results showed a decrease in EBL and lesser
      decrease in pre- and postoperative hemoglobin and hematocrit levels as compared
      with cases in which no vascular ligation was performed when corrected for tumor
      volume.

PMID- 30196173
TI  - Better Hemodynamics and Less Antihypertensive Medication: Comparison of Scalp
      Block and Local Infiltration Anesthesia for Skull-Pin Placement in Awake Deep
      Brain Stimulation Surgery.
AB  - OBJECTIVE: In deep brain stimulation (DBS) surgery, acute high blood pressure
      (BP) is a risk factor for intracranial hemorrhage. To minimize pain and
      hypertensive conditions, sufficient local anesthesia is mandatory. We evaluated
      whether local instillation of anesthetics (LA) or a scalp block (SB) is superior
      concerning intraoperative hemodynamics and analgesia. METHODS: We retrospectively
      analyzed intraoperative cardiovascular parameters and perioperative medication in
      47 patients (LA = 29, SB = 18) undergoing DBS surgery. Primary study end points
      were intraoperative systolic BP and heart rate. Secondary end points were use of
      intraoperative antihypertensives and perioperative analgesics. RESULTS: Patients
      who had SB showed lower mean systolic BP and heart rate compared with patients
      who had LA. Patients who had LA required more antihypertensive medication to
      stabilize BP. BP was higher, particularly during the first 90 minutes of surgery,
      in patients who had LA. Thereafter, more antihypertensives were necessary to
      achieve sufficient BP control in the LA group. The dose of analgesics did not
      differ significantly between both groups during and after surgery. CONCLUSIONS:
      Our data suggest that SB might be superior to LA for DBS surgery with respect to
      BP control and hemodynamics. The need for analgesics does not differ
      substantially between both anesthetic treatment options.

PMID- 30196174
TI  - One Center's Experience with Hybrid Technique for Lumbar Spine Instrumentated
      Surgeries: Evaluation of Different Instrumentation Systems and Their Management.
AB  - BACKGROUND: Minimally invasive surgery (MIS) has been providing many solutions in
      spine surgery, and several technical variations and instrumentation systems are
      available. The aim of our study is to investigate the best system to perform a
      hybrid technique in lumbar spine fusion procedures. METHODS: Sixteen patients
      were enrolled and randomly assigned to 1 of the 4 groups reported later. The
      first step in any case was midline incision, fascia exposure, and, using trocars,
      intravertebral transpedicle Kirschner wires (KWs) positioning through the fascia.
      Group definitions were A) KWs were affixed to surgical towels; B) screws with
      metal extensors were placed and KWs removed; C) screws with plastic extensors
      (K2M) were placed and those extensors were affixed to surgical towels; and D)
      screws without extensors or tulips (Nuvasive) were positioned. We locked the
      system at the end of procedure, after posterior decompression and translumbar
      interbody fusion cage placement. Procedures' features were rated using properly
      designed questionnaires by surgeons. RESULTS: Metal extensors were rated lower
      than other systems in any aspect. C and D groups' procedures were higher rated
      than those in A and B in all examined fields. Furthermore, group D's procedures
      were reported more comfortable during facetectomy, diskectomy, and cage
      placement. Surgeons reported Precept Modular (Nuvasive) as the most comfortable
      and useful system in the hybrid technique. CONCLUSIONS: Precept Modular seems to
      be the most useful system when performing hybrid technique in lumbar fusion
      procedures. Furthermore, it results in the only one that provides the opportunity
      to easily and quickly switch from minimally invasive surgery to open surgery,
      avoiding muscles' injuries.

PMID- 30196175
TI  - Pediatric Case of Li-Fraumeni Syndrome Complicated with Supratentorial Anaplastic
      Ependymoma.
AB  - BACKGROUND: Li-Fraumeni syndrome is a genetic disease that is caused by mutation
      of the tumor suppressor gene TP53. Patients with this syndrome may develop
      multiple malignant neoplasms including brain tumors. We herein report the first
      case of Li-Fraumeni syndrome in which development of supratentorial anaplastic
      ependymoma led to difficulty in terms of selecting the optimal postoperative
      therapeutic protocol. CASE DESCRIPTION: A 7-year-old boy experiencing a
      convulsive attack was brought to our institute. He underwent surgical tumor
      resection, and magnetic resonance imaging of the head revealed a tumor-like
      lesion in the right parietal lobe. Although adjuvant radiotherapy was performed
      after total tumor resection, a focal recurrent lesion appeared soon afterward. We
      initiated chemotherapy with bevacizumab after resection of the recurrent lesion,
      but bevacizumab was unable to control tumor progression. At this writing, he
      remains bedridden and requires tube feeding and artificial ventilation.
      CONCLUSION: Since Li-Fraumeni syndrome is a genetic disease that is caused by
      mutation of the tumor suppression gene TP53, patients should generally not be
      treated with radiotherapy or alkylating agents that induce deoxyribonucleic acid
      damage. However, if the prognostic benefit of postoperative adjuvant therapies is
      thought to surpass the risk of long-term secondary cancer, it is appropriate to
      consider these therapies after consultation with the patient and family.
      Postoperative treatment protocols are controversial, and their role should be
      further explored in cases of Li-Fraumeni syndrome complicated with malignant
      gliomas.

PMID- 30196176
TI  - Unfavorable Vascular Anatomy Is Associated with Increased Revascularization Time
      and Worse Outcome in Anterior Circulation Thrombectomy.
AB  - BACKGROUND: Reperfusion time influences patient outcome in mechanical
      thrombectomy for large vessel occlusion. We analyzed anatomic features that could
      be used to make preoperative and intraoperative decisions to minimize
      revascularization time. METHODS: We reviewed a prospectively maintained database
      for patients with stroke evaluated from February 2015 to July 2016. Patients
      received a score based on bovine arch, aortic arch, and internal carotid artery
      dolichoarteriopathy (B.A.D. score), which we correlated with procedural times and
      outcomes. Univariate analysis was performed to identify predictors of procedural
      times, revascularization, complications, and outcome. Relevant variables were
      assessed via multivariate regression. RESULTS: We identified 61 patients (31 men)
      who underwent transfemoral thrombectomy. Mean puncture to reperfusion time was 46
      minutes. Age >75 years (odds ratio [OR] = 3.98; 95% confidence interval [CI],
      1.17-13.54; P = 0.027) and high B.A.D. score (OR = 2.55; 95% CI, 1.17-5.57; P =
      0.019) were significant predictors of puncture to reperfusion time >40 minutes.
      Mean puncture to first-pass time was 24 +/- 14.2 minutes. Age >65 years (OR =
      4.68; 95% CI, 1.07-20.55; P = 0.041) and high B.A.D. score (OR = 2.84; 95% CI,
      1.18-6.85; P = 0.020) were independently predictive of time to first pass >20
      minutes. Lower scores predicted higher Thrombolysis In Cerebral Infarction score
      (OR = 0.07; 95% CI, 0.01-0.81; P = 0.033). Higher scores predicted hemorrhagic
      transformation (OR = 4.8; 95% CI, 1.19-12.29; P = 0.024) and modified Rankin
      Scale score >4 (OR = 3.0; 95% CI, 1.15-7.92; P = 0.025) after thrombectomy.
      CONCLUSIONS: Bovine variation, aortic arch type, and internal carotid artery
      dolichoarteriopathy are associated with increased revascularization time and poor
      outcomes in thrombectomy. We developed the B.A.D. score to predict reperfusion
      time and outcomes, demonstrating need for preoperative anatomic evaluation to
      guide treatment.

PMID- 30196177
TI  - Precision Treatment of Adult Lumbar Degenerative Scoliosis Complicated by Lumbar
      Stenosis with the Use of Selective Nerve Root Block.
AB  - BACKGROUND: Use of short-segment or long-segment fusion is controversial in
      treatment of adult lumbar degenerative scoliosis (ALDS). The aim of this study
      was to explore efficacy and feasibility of precision treatment of ALDS with
      selective nerve root block. METHODS: From January 2014 to January 2016, a
      retrospective study of 23 patients with ALDS treated with precision short-segment
      surgery with at least 2-year follow-up was performed. Fixation segment was
      determined by selective nerve root block. Visual analog scale and Oswestry
      Disability Index (ODI) were evaluated preoperatively and at 2-year follow-up.
      Radiographic measurements included Cobb angle of lumbar curve, lumbar lordosis,
      sacrum slope, and pelvic tilt. Radiographic evaluation of fusion integrity was
      performed based on Bridwell interbody fusion grading system at final follow-up.
      RESULTS: Mean follow-up time was 25.2 +/- 1.4 months. Average lumbar curve was
      21.6 degrees  +/- 7.4 degrees  preoperatively and 11.2 degrees  +/- 6.5 degrees 
      at final follow-up (P < 0.01), with correction rate of 48.1%. Lumbar lordosis
      changed from -37.1 degrees  +/- 12.9 degrees  to -42.1 degrees  +/- 10.5 degrees 
      at final follow-up (P < 0.01). Mean visual analog scale back pain scores
      decreased from 6.0 +/- 1.8 preoperatively to 1.5 +/- 0.8 at final follow-up (P <
      0.01), and mean visual analog scale leg pain scores decreased from 8.1 +/- 0.6
      preoperatively to 1.3 +/- 1.3 at final follow-up (P < 0.01). Oswestry Disability
      Index score improved from 60.9% +/- 15.7% preoperatively to 22.1% +/- 11.6% at
      final follow-up (P < 0.01). All patients achieved grade I fusion at final
      evaluation. One patient (4%) needed further surgical intervention. CONCLUSIONS:
      Precision treatment of ALDS with selective nerve root block can achieve favorable
      clinical outcomes and good fusion with less surgical injury and low
      complications. Deformity correction is limited, which requires further study.

PMID- 30196178
TI  - Expression of Cyclin E/Cdk2/p27Kip1 in Growth Hormone Adenomas.
AB  - OBJECTIVE: The present study was conducted to evaluate the levels of Cdk2, cyclin
      E, p21, and p27 in growth hormone adenomas (GHPAs) and analyze their association
      with clinicopathologic features. METHODS: We collected 46 GHPA specimens and
      clinical materials from March 2012 to December 2015 at Beijing Tiantan Hospital.
      We analyzed the expression of Cdk2, cyclin E, p21, and p27 using
      immunohistochemistry, quantitative real-time polymerase chain reaction, Western
      blot, and methylation-specific polymerase chain reaction and sequencing. RESULTS:
      The levels of cyclin E and Cdk2 were much greater in the invasive group than in
      the noninvasive group (P < 0.05). Significant differences were found between
      cyclin E and p21 and tumor size (P < 0.05) and between cyclin E expression and
      invasion (P < 0.05). Tumors were more likely to require whole resection in
      patients with low cyclin E expression (P < 0.05). The high-level p27 group had
      better progression-free survival than did the low-level p27 group (P < 0.01).
      Quantitative real-time polymerase chain reaction and Western blot analysis
      revealed a similar trend for Cdk2, cyclin E, p21, and p27 protein levels in
      growth hormone specimens (P < 0.01). An average of 33 CpG sites per sample were
      analyzed using matrix-assisted laser desorption ionization time-of-flight mass
      array, and in 7 of the 33 CpG sites, the methylation levels of p27 were >50%.
      Statistically significant differences were found in 4 CpG sites between the
      invasive and noninvasive specimens (P < 0.01). CONCLUSIONS: Overexpression of
      cyclin E/Cdk2 and loss of p27 appears to be associated with a poor prognosis and
      might play a role in the treatment of GHPAs in the future.

PMID- 30196179
TI  - Sinonasal Non-Intestinal-Type Adenocarcinoma: A Retrospective Review of 22
      Patients.
AB  - OBJECTIVE: To analyze outcomes and prognostic factors of sinonasal nonsalivary
      non-intestinal-type adenocarcinoma (n-ITAC.) METHODS: A retrospective review of
      22 consecutive patients with n-ITAC was performed. RESULTS: Average follow-up
      time was 77 months. The 5-year overall survival and disease-specific survival
      were 95.2%. The 5-year overall survival and disease-specific survival were 100%
      for pT1, pT2, and pT3 tumors and 83.3% for pT4a and pT4b tumors; 100% for G1
      tumors and 87.5% for G3 tumors; and 100% for tumors with negative surgical margin
      and 50% for tumors with positive surgical margin. Stage, grade, and surgical
      margins were independent prognostic factors. Adjuvant radiotherapy was performed
      for high-grade and high-stage tumors. CONCLUSIONS: Surgery followed by
      radiotherapy has remained a mainstay for management of n-ITAC, and the endoscopic
      transnasal approach, when correctly planned and indicated, is the surgery of
      choice. Adjuvant radiotherapy is recommended in cases of high-stage (T3 and T4)
      and high-grade tumors. n-ITAC is associated with a favorable outcome. High grade,
      pT4 stage, and positive surgical margins are independent negative prognostic
      factors.

PMID- 30196180
TI  - Optimization of fermentation-relevant factors: A strategy to reduce ethanol in
      red wine by sequential culture of native yeasts.
AB  - Current consumer preferences are determined by well-structured, full-bodied wines
      with a rich flavor and with reduced alcohol levels. One of the strategies for
      obtaining wines with reduced ethanol content is sequential inoculation of non
      Saccharomyces and Saccharomyces cerevisiae yeasts. However, different factors
      affect the production of metabolites like ethanol, glycerol and acetic acid by
      inoculated yeasts. In order to obtain low alcohol wines without quality loss, the
      aims of our study were: i) to determine optimum conditions (fermentation
      temperature and time of permanence and initial inoculum size of the non
      Saccharomyces population at the beginning of the process, prior to inoculation
      with S. cerevisiae); ii) to validate the optimized factors; and iii) to assess
      sensory quality of the wines obtained after validation. Two combinations of
      yeasts were used in this study: Hanseniaspora uvarum BHu9/S. cerevisiae BSc114
      and Candida membranaefaciens BCm71/S. cerevisiae BSc114. Optimization of three
      fermentation factors that affect to non-Saccharomyces yeasts prior to S.
      cerevisiae inoculation was carried out using a Box-Behnken experimental design.
      Applying the models constructed by Response Surface Methodology, the lowest
      ethanol production by H. uvarum BHu9/S. cerevisiae BSc114 co-culture was obtained
      when H. uvarum BHu9 was inoculated 48 h 37 min prior to S. cerevisiae
      inoculation, at a fermentation temperature of 25  degrees C and at an initial
      inoculum size of 5 * 106 cells/mL. Lowest alcohol production with C.
      membranaefaciens BCm71/S. cerevisiae BSc114 was observed when C. membranaefaciens
      BCm71 was inoculated 24 h 15 min prior to S. cerevisiae at a fermentation
      temperature of 24.94  degrees C and at an initial inoculum size of 2.72 * 106
      cells/mL. The optimized conditions of the two co-cultures were subsequently
      submitted to lab-scale validation. Both proposed strategies yielded ethanol
      levels that were significantly lower than control cultures (S. cerevisiae). Wines
      fermented with non-Saccharomyces/Saccharomyces co-cultures under optimized
      conditions were also associated with higher aromatic complexity characterized by
      the presence of red fruit aromas, whereas wines obtained with S. cerevisiae
      BSc114 were described by parameters linked with high ethanol levels.

PMID- 30196181
TI  - Impact of high on-aspirin platelet reactivity on outcomes following successful
      percutaneous coronary intervention with drug-eluting stents.
AB  - BACKGROUND: Whether high on-aspirin platelet reactivity (HAPR) confers an
      increased risk of adverse outcomes after percutaneous coronary intervention (PCI)
      remains unclear. We sought to examine the specific relationship between HAPR and
      clinical outcomes in ADAPT-DES. METHODS: A total of 8,526 "all-comer" patients in
      the ADAPT-DES registry who underwent placement of drug-eluting stents (DES) and
      were treated with aspirin and clopidogrel were assessed to measure platelet
      reactivity. HAPR was characterized as >=550 aspirin reaction units and high on
      clopidogrel platelet reactivity as >208 P2Y12 reaction units. Univariable and
      propensity-adjusted multivariable analyses were used to assess the relationship
      between HAPR and clinical outcomes. RESULTS: HAPR was present in 478 (5.6%)
      patients. Patients with HAPR were older and had more comorbid illnesses and more
      complex coronary anatomy. During 2-year follow-up, HAPR was not associated with
      increased rates of major adverse cardiac events (MACE), stent thrombosis,
      myocardial infarction, or all-cause mortality. In propensity-adjusted
      multivariable analyses, HAPR was not an independent predictor of MACE after
      successful PCI (multivariable adjusted hazard ratio: 1.04; 95% CI 0.64-1.69, P =
      .87). Nor was HAPR associated with reduced bleeding. Even among patients with
      concomitant high on-clopidogrel platelet reactivity, HAPR was not associated with
      worse ischemic outcomes (adjusted hazard ratio for 2-year MACE: 1.06; 95% CI 0.55
      2.00, P = .87). CONCLUSIONS: HAPR was infrequently present in a large registry of
      patients undergoing PCI. There was no clear relationship between HAPR and 2-year
      clinical outcomes. Investigations of antiplatelet regimens without aspirin after
      DES implantation are ongoing and should inform future management of patients
      undergoing PCI.

PMID- 30196182
TI  - Scalable novel PVDF based nanocomposite foam for direct blood contact and cardiac
      patch applications.
AB  - Scalable novel beta phase polyvinylidene fluoride-poly(methyl methacrylate) (PVDF
      PMMA) polymer blend based nanocomposite foam with hydroxyapatite (HAp) and
      titanium dioxide (TiO2) as nanofillers (beta-PVDF-PMMA/HAp/TiO2) (beta-PPHT-f),
      was prepared by using salt etching assisted solution casting method. The prepared
      beta-PPHT-f nanocomposite material was characterized using XRD, FT-IR, SEM-EDS.
      The XRD and FTIR results confirmed the formation of beta phase of beta-PPHT-f.
      The SEM and EDS results confirmed the formation of high porous structured closed
      cell type morphology of beta-PPHT-f. It also, confirmed the uniform distribution
      of Ti, Ca, P, N and O, in beta-PPHT-f. Contact angle measurements performed using
      sessile drop method with water and EDTA treated blood (EDTA blood) as probe
      liquids revealed that beta-PPHT-f is hydrophilic with contact angle of 48.2
      degrees  as well as hemophilic with contact angle of 13.7 degrees . Porosity,
      fluid absorption and retention investigation by gravimetric analysis revealed
      that beta-PPHT-f was 89.2% porous and can absorb and retain 139.15% and 87.05% of
      water and blood, respectively. The hemolysis assay performed as per ASTM F756
      procedure revealed that beta-PPHT-f is non hemolytic. Also, the Leishman stained
      blood smears prepared from whole blood incubated with beta-PPHT-f for 3, 4, 5 and
      6 h at 37  degrees C revealed that the blood cells were not affected by beta-PPHT
      f, its surface morphology and elemental composition. H9c2 cell line studies on a
      transparent film prepared using beta-PPHT-f revealed that the elemental
      composition of the nanocomposite favored H9c2 cell adhesion and differentiation.
      All the characterization results indicate that the newly developed scalable novel
      beta-PPHT-f is hemocompatible and cardiomyocyte compatible, suggesting it as a
      useful material for direct blood contact and cardiac patch applications.

PMID- 30196183
TI  - Influence of primers on the properties of the adhesive interface between resin
      composite luting cement and fiber-reinforced composite.
AB  - OBJECTIVES: The purpose of this study was to characterize the adhesive interface
      formed due to the dissolving capability of 4 primer systems into pre-polymerized
      semi-interpenetrating polymer network (semi-IPN)-based fiber-reinforced composite
      (FRC) and luting cement. MATERIALS AND METHODS: Semi-IPN FRC (everStick C&B,
      StickTech) prepregs stored for various durations (at 4  degrees C; 1, 1.5, and 3
      years) were used to fabricate the specimens. FRC specimens (n = 10) were light
      cured and treated with primers before adhering a luting cement onto them. Each
      age group was divided into four subgroups according to the primer used: no
      priming, a dimethacrylate adhesive primer, universal primer, and primer intended
      for composite surfaces. The degree of monomer conversion (DC%) of the luting
      cement; nanohardness, elastic modulus and structural information of the luting
      cement-FRC adhesive interface were measured. RESULTS: According to analysis of
      variance (P <= 0.05), no statistical difference was observed in the DC% among the
      tested groups. However, both universal and composite primers showed increased
      nanohardness in 1- and 1.5-year-aged groups. The highest nanohardness (0.55 +/-
      0.21 GPa) and elastic modulus (14.27 +/- 5.19 GPa) were observed in specimens of
      1-year-aged FRC primed with the application of universal primer. Raman
      spectroscopy and scanning electron microscopy examination confirmed the presence
      of poly(methyl methacrylate) at the interface when the FRC prepregs were aged for
      3 years before use. CONCLUSION: Both primers improved diffusion of monomers of
      composite luting cement into the polymerized semi-IPN polymer structure and
      possible covalent binding with pendant methacrylate groups in the polymer matrix
      of FRC. The diffusing capability of universal and composite primers might
      increase the opportunity to form solid adhesive interface bonding between the FRC
      and composite luting cement.

PMID- 30196184
TI  - A three-dimensional micromechanical model of brain white matter with histology
      informed probabilistic distribution of axonal fibers.
AB  - This paper presents a three-dimensional micromechanical model of brain white
      matter tissue as a transversely isotropic soft composite described by the
      generalized Ogden hyperelastic model. The embedded element technique, with
      corrected stiffness redundancy in large deformations, was used for the embedment
      of a histology-informed probabilistic distribution of the axonal fibers in the
      extracellular matrix. The model was linked to a multi-objective, multi-parametric
      optimization algorithm, using the response surface methodology, for
      characterization of material properties of the axonal fibers and extracellular
      matrix in an inverse finite element analysis. The optimum hyperelastic
      characteristics of the tissue constituents, obtained based on the axonal and
      transverse direction test results of the corona radiata tissue samples, indicated
      that the axonal fibers were almost thirteen times stiffer than the extracellular
      matrix under large deformations. Simulation of the same tissue under a different
      loading condition, as well as that of another white matter tissue, i.e., the
      corpus callosum, in the axonal and transverse directions, using the optimized
      hyperelastic characteristics revealed tissue responses very close to those of the
      experiments. The results of the model at the sub-tissue level indicated that the
      stress concentrations were considerably large around the small axons, which might
      contribute into the brain injury.

PMID- 30196185
TI  - Replication and bioactivation of Ti-based alloy scaffold macroscopically
      identical to cancellous bone from polymeric template with TiNbZr powders.
AB  - In the present work, a new type of porous Ti-based alloy scaffold with high
      porosity (about 75%) and interconnected pores in the range of 300-1000 um was
      fabricated by polymeric foam replication method with TiNbZr powders. This porous
      scaffold, which is consisted with major beta phase Ti and minor alpha Ti phase,
      exhibits a compressive strength of 14.9 MPa and an elastic modulus of 0.21 GPa,
      resembling the mechanical properties of nature human cancellous bone (sigma = 10
      50 MPa, E = 0.01-3.0 GPa). To improve its osteogenic potential, a bioactive
      nanostructural titanate network coating was applied to the scaffold surface using
      hydrothermal treatment. The bone-like apatite inducing ability of the treated
      scaffold was systemically assessed using SBF immersion during 3-28 days. The
      nanostructural titanate network coated on porous TiNbZr scaffold is favorable for
      apatite nucleation and subsequent growth due to the hydrolysis of titanate. The
      results suggest that highly porous TiNbZr scaffolds with an appropriate bioactive
      coating, which was fabricated in this study, could be potentially used for bone
      tissue engineering application.

PMID- 30196186
TI  - Fatigue behavior and surface characterization of a Y-TZP after laboratory
      grinding and regeneration firing.
AB  - This study evaluated the effect of grinding and regeneration firing on the
      flexural fatigue limit and surface characterization of LavaTM Y-TZP ceramic.
      Forty bar-shaped specimens with 20 * 4.0 * 1.2 mm constituted the as-sintered
      group (AS = control group), and 80 specimens with 20 * 4.0 * 1.5 mm were ground
      with cylindrical laboratory stone under water-cooling (WG) or in a dry condition
      (G) to reach 1.2 mm in thickness. Half of specimens were submitted to
      regeneration firing (1000  degrees C, 30 min), forming the groups AS/R, WG/R and
      G/R. Fatigue limit (500,000 cycles, 10 Hz) was determined by staircase method in
      a 4-point flexural fixture. Data were analyzed by 2-way ANOVA and Tukey HSD tests
      (alpha = 0.05). The surface topography (n = 3) and fracture area (n = 3) were
      evaluated by SEM. Samples were also analyzed by Rietveld refinement from X-ray
      diffraction data. ANOVA revealed significant differences (P < .001) for grinding
      protocol, regeneration firing and their interaction. In the groups not submitted
      to regeneration firing, the mean flexural fatigue limit of WG was higher (P <
      .05) than that of G and AS, with no statistical difference between each other (P
      > .05). After regeneration firing the inequality WG>AS>G (P < .05) was observed.
      The regeneration firing increased the fatigue limit of AS group and decreased
      those of G and WG groups (P < .05). Grinding protocols created evident grooves on
      zirconia surface. Failures initiated on tensile side of all specimens. The
      percentages (wt%) of monoclinic phase before cyclic loading were: AS (7.4), AS/R
      (6.5), G (2.8), G/R (0.0), WG (4.4), WG/R (0.0); and after cyclic loading: AS
      (8.6), AS/R (1.2), G (2.4), G/R (5.7), WG (6.3), WG/R (0.0). Wet grinding did not
      compromise the fatigue limit of zirconia, increasing its mechanical strength.
      Regeneration firing reduced the fatigue limit of ground samples, despite reducing
      the amount of monoclinic phase in all experimental conditions.

PMID- 30196187
TI  - Femoral entheseal shape and attachment angle as potential risk factors for
      anterior cruciate ligament injury.
AB  - Although non-contact human ACL tears are a common knee injury, little is known
      about why they usually fail near the femoral enthesis. Recent histological
      studies have identified a range of characteristic femoral enthesis tidemark
      profiles and ligament attachment angles. We tested the effect of the tidemark
      profile and attachment angle on the distribution of strain across the enthesis,
      under a ligament stretch of 1.1. We employed a 2D analytical model followed by 3D
      finite element models using three constitutive forms and solved with
      ABAQUS/Standard. The results show that the maximum equivalent strain was located
      in the most distal region of the ACL femoral enthesis. It is noteworthy that this
      strain was markedly increased by a concave (with respect to bone) entheseal
      profile in that region as well as by a smaller attachment angle, both of which
      are features more commonly found in females. Although the magnitude of the
      maximum equivalent strain predicted was not consistent among the constitutive
      models used, it did not affect the relationship observed between entheseal shape
      and maximum equivalent strain. We conclude that a concave tidemark profile and
      acute attachment angle at the femoral ACL enthesis increase the risk for ACL
      failure, and that failure is most likely to begin in the most distal region of
      that enthesis.

PMID- 30196188
TI  - The role of water in the initial sliding of nacreous tablets: Findings from the
      torsional fracture of dry and hydrated nacre.
AB  - Nacre exhibits remarkable mechanical properties resulting from its hierarchical
      brick-and-mortar structures. By using pure shear stresses of torsion, we
      demonstrate how nacre resists the initial tablet sliding by tuning its nanoscale
      toughening mechanisms in dry and hydrated conditions. In hydrated nacre, hydrogen
      bonds between water molecules and organic matrices provide temporal paths for
      stress redistributions, through which the shear resistance is gradually
      transferred from mineral bridges to contacted nanoasperities. In the subsequent
      sliding, dynamical interactions between nacreous tablets enable substantial
      plasticity before the catastrophic failure of hydrated nacre. Our findings should
      help pursuing further insights into the interfacial behavior of natural and
      artificial laminated nanomaterials under different conditions.

PMID- 30196189
TI  - Collective cell polarization and alignment on curved surfaces.
AB  - Curvature as an important topological parameter of 3D extra-cellular matrix has
      drawn growing attention in recent years. But the underlying mechanism that
      curvature influences cell behaviors has remained unknown. In this study, we
      seeded cells on semi-cylindrical and hemispheric surfaces and tested cell
      alignment and polarization. We found that the surface curvature has profound
      effect on cell behaviors. With the decrease of diameter of the cylinder/sphere
      (i.e. increase of curvature), the cells would more preferentially align and
      polarize with large aspect ratio in the axial/peripheral direction. And the
      behaviors of the alignment and polarization were position-dependent. For example,
      at the end of the cylinder, the cells preferred to align circumferentially; while
      in the interior region, the cells preferred to align in the axial direction. We
      showed that the cell polarization and alignment were closely correlated with the
      in-plane stresses in cell layer. That is, the cell polarization and alignment
      were controlled by the maximum shear stress, which drove cells to align and
      polarize along the maximum principal stress. The curvature could influence the
      magnitude of the maximum shear stress and thus regulate cell behaviors. This
      study provided important insights into the mechanisms of surface curvature
      influencing cell behaviors in tissue morphogenesis. In addition, our theory of
      the stress dependent cellular polarity provides a generalized interpretation of
      the curvature and edge effects which might be extended to understand other steric
      effects in cell behaviors.

PMID- 30196190
TI  - Artesunate-induced mitophagy alters cellular redox status.
AB  - Artesunate (ART) is a prominent anti-malarial with significant anti-cancer
      properties. Our previous studies showed that ART enhances lysosomal function and
      ferritin degradation, which was necessary for its anti-cancer properties. ART
      targeting to mitochondria also significantly improved its efficacy, but the
      effect of ART on mitophagy, an important cellular pathway that facilitates the
      removal of damaged mitochondria, remains unknown. Here, we first observed that
      ART mainly localizes in the mitochondria and its probe labeling revealed that it
      binds to a large number of mitochondrial proteins and causes mitochondrial
      fission. Second, we found that ART treatment leads to autophagy induction and the
      decrease of mitochondrial proteins. When autophagy is inhibited, the decrease of
      mitochondrial proteins could be reversed, indicating that the degradation of
      mitochondrial proteins is through mitophagy. Third, our results showed that ART
      treatment stabilizes the full-length form of PTEN induced putative kinase 1
      (PINK1) on the mitochondria and activates the PINK1-dependent pathway. This in
      turn leads to the recruitment of Parkin, sequestosome 1 (SQSTM1), ubiquitin and
      microtubule-associated proteins 1A/1B light chain 3 (LC3) to the mitochondria and
      culminates in mitophagy. When PINK1 is knocked down, ART-induced mitophagy is
      markedly suppressed. Finally, we investigated the effect of mitophagy by ART on
      mitochondrial functions and found that knockdown of PINK1 alters the cellular
      redox status in ART-treated cells, which is accompanied with a significant
      decrease in glutathione (GSH) and increase in mitochondrial reactive oxidative
      species (mROS) and cellular lactate levels. Additionally, knockdown of PINK1
      leads to a significant increase of mitochondrial depolarization and more cell
      apoptosis by ART, suggesting that mitophagy protects from ART-induced cell death.
      Taken together, our findings reveal the molecular mechanism that ART induces
      cytoprotective mitophagy through the PINK1-dependent pathway, suggesting that
      mitophagy inhibition could enhance the anti-cancer activity of ART.

PMID- 30196192
TI  - The detection of significant fractures in suspected infant abuse.
AB  - OBJECTIVE: Skeletal survey is a commonly used means of detecting fractures in
      infants, and is used as a screen in suspected cases of physical abuse. It is
      recognised that in live infants, a repeat survey some days after a suspected
      episode of injury will detect more fractures than one taken shortly after the
      suspected injury, indicating that the latter lacks sensitivity. In infants who
      die soon after a suspected episode of physical abuse, the managing clinicians do
      not have the option of a second survey; however there is the opportunity for the
      microscopic examination of bones removed at autopsy. Increasingly Osteoarticular
      Pathology at the Manchester University NHS Foundation Trust (MFT) is being sent
      samples of bones from infants suspected of inflicted injury for histological
      examination, both from bones with fractures detected at autopsy or skeletal
      survey and from posterior ribs and long bone metaphyses (sites of significance in
      assessing for abusive injury) when there is no evidence of fracture on skeletal
      survey or autopsy. Here we report the results of an audit of the anonymised data
      from a series of such cases, to establish the sensitivity of skeletal survey (SS)
      to detect fractures and to define the medico-legal value of submitting bones for
      histological examination. METHODS: This was an audit of skeletal injuries in 38
      infants aged <18 months presenting to MFT for specialist histopathological
      evaluation of suspected non-accidental fractures between January 2011 and June
      2017. Histopathological examination was performed on all bones submitted and
      compared with contact radiography of isolated bones and post-mortem skeletal
      surveys undertaken by specialist paediatric or musculoskeletal radiologists for
      the presence of fracture. RESULTS: A total of 318 fractures were detected
      histologically; of these, 178 (56%) were of the ribs, 119 (37.5%) were of major
      limb long bones, 10 (3%) were of the skull, and 11 (3.5%) were recorded as
      'other'. Excluding refractures, skeletal survey detected 54% of the fractures
      recorded histologically. No fractures were detected radiologically that were not
      seen histologically. Generally, for skeletal survey, detection rates improved
      with the age of the lesion, and rib fractures were more difficult to detect than
      long bone fractures. Ribs 5-8 were the most frequently fractured ribs, and
      metaphyses around the knee accounted for most metaphyseal limb long bone
      fractures undetected by SS. CONCLUSION: In infants coming to post-mortem,
      histopathology is more sensitive than SS for the detection of clinically
      significant fractures. In children suspected of non-accidental injuries but with
      negative or equivocal SS, sampling of the anterior and posterior end of ribs 5-8
      and the bones around the knee for histological examination could reveal
      clinically unsuspected fractures and significant evidence of physical abuse. 71%
      of infants showed evidence of old fractures typical of non-accidental injury.

PMID- 30196193
TI  - Alterations in the parameters of classic, global, and innovative assays of
      hemostasis caused by sample transportation via pneumatic tube system.
AB  - BACKGROUND: Pneumatic tube system (PTS) is an integral part of large medical
      facilities providing rapid interconnection between units within the hospital and
      often used to transport blood samples. The aim of our study was to compare a wide
      variety of hemostasis assays to identify assays sensitive to this transport
      method and diagnostic relevance of the alterations. METHODS: Routine coagulation
      and platelet tests (APTT, PT, TT, fibrinogen, light transmission aggregometry
      (LTA) with ADP, collagen, ristomycin and epinephrine), whole blood flow cytometry
      platelet function test (levels of CD42b, CD61, CD62P, PAC1, annexin V binding and
      mepacrine release) and global coagulation tests (thromboelastography (TEG),
      thrombin generation (TGT), thrombodynamics (TD), thrombodynamics-4D (TD-4D)) were
      determined in PTS- and manually transported samples of 10 healthy volunteers.
      RESULTS: There were no significant differences between the values of APTT, PT, TT
      or fibrinogen between the samples transported by PTS or manually. The results for
      LTA demonstrated increase in the collagen-induced aggregation (84 +/- 7% versus
      73 +/- 5%), while the response to epinephrine was decreased (58 +/- 20% versus 72
      +/- 7.4%). Flow cytometry-based platelet function test showed a pre-activation of
      platelets by PTS-transportation while all integral assays of coagulation tested
      in the present study (TEG, TGT, TD, TD-4D) demonstrated a hypercoagulation shift.
      CONCLUSIONS: Transportation by PTS caused significant shifts in parameters of
      functional and integral assays that exceeded parameter variation values and
      sometimes even were comparable to normal ranges. The results obtained in this
      study indicate that using of PTS for such assays may cause sufficient alterations
      of results and can lead to patient's mistreatment.

PMID- 30196191
TI  - Putting xanthine oxidoreductase and aldehyde oxidase on the NO metabolism map:
      Nitrite reduction by molybdoenzymes.
AB  - Nitric oxide radical (NO) is a signaling molecule involved in several
      physiological and pathological processes and a new nitrate-nitrite-NO pathway has
      emerged as a physiological alternative to the "classic" pathway of NO formation
      from L-arginine. Since the late 1990s, it has become clear that nitrite can be
      reduced back to NO under hypoxic/anoxic conditions and exert a significant
      cytoprotective action in vivo under challenging conditions. To reduce nitrite to
      NO, mammalian cells can use different metalloproteins that are present in cells
      to perform other functions, including several heme proteins and molybdoenzymes,
      comprising what we denominated as the "non-dedicated nitrite reductases". Herein,
      we will review the current knowledge on two of those "non-dedicated nitrite
      reductases", the molybdoenzymes xanthine oxidoreductase and aldehyde oxidase,
      discussing the in vitro and in vivo studies to provide the current picture of the
      role of these enzymes on the NO metabolism in humans.

PMID- 30196194
TI  - Deep-vein thrombosis in Europe - Burden of illness in relationship to healthcare
      resource utilization and return to work.
AB  - OBJECTIVES: Deep-vein thrombosis (DVT) forms a major healthcare burden in Europe,
      but exact estimates concerning the economic burden on society are lacking. This
      study reports results from the PREFER in VTE study concerning resource
      utilization and absence from work in DVT patients. METHODS: The PREFER in VTE
      registry was a prospective, observational, multicenter study carried out in
      Europe (France, Italy, Spain, the UK, and DACH [Germany, Switzerland and
      Austria]), designed to provide data concerning treatment patterns, resource
      utilization, mortality and quality of life. Patients with a first-time and/or
      recurrent DVT, were recruited and followed for 12 months. Data about resource
      utilization concerns resource utilization related to DVT. Specifically, treatment
      pattern, re-hospitalization rate, length of hospital stay, ambulatory/office
      visit, and proportion of patients returning to work, were analyzed and presented.
      Subgroup analysis by country and active cancer were also conducted. The length of
      hospital stay was analyzed as a function of demographics, previous events and co
      morbidities using zero-inflated binomial negative regression. Similarly, time
      until return to work was analyzed using Cox regression. RESULTS: A total of 2056
      patients with DVT were recruited, with an average age of 60 years. Patients with
      active cancer were mostly treated with heparin (83.9%), while patients without
      active cancer were treated with combinations of heparin, VKA and DOACs. DOACs
      were less often used in Spain and Italy (<7.0%). Following the management of
      their initial DVT 20.5% of the patients with and 12.2% of patients without active
      cancer (n = 88; n = 1462) were hospitalized for on average 8.2 and 10.1 days,
      respectively. The hospitalization-rate was highest in Italy (16.7%) and lowest in
      France (7.7%). Furthermore, the average length of stay was highest in Italy (16.6
      days) and lowest in DACH (5.2 days). Physician visits were highest in DACH (9.3),
      lowest in the UK (2.6). Of those working, 50% returned to work at 1 month; >30%
      did not return to work within the year. CONCLUSIONS: Medical treatment of DVT
      differed between patients with active cancer and those without. Post-VTE or VTE
      related resource utilization differs remarkably between countries. Work-loss
      seems high, but questions may be raised concerning the causality due to the
      presence of co-morbidities.

PMID- 30196195
TI  - Efficacy and safety of anticoagulant agents in patients with venous
      thromboembolism and cancer: A network meta-analysis.
AB  - BACKGROUND: Low-molecular-weight heparins (LMWHs) are the recommended treatment
      for cancer-associated venous thrombosis (CAT). Recent evidences suggest a role
      for direct-acting oral anticoagulants (DOACs) in this clinical setting. METHODS:
      To evaluate the efficacy and safety of different anticoagulants we performed a
      network meta-analysis of RCTs including patients with CAT treated with LMWHs,
      vitamin K antagonists (VKAs) or DOACs. MEDLINE and EMBASE were searched up to
      February 2018. The primary efficacy and safety outcomes were recurrent VTE and
      major bleeding, respectively. RESULTS: Overall, 4720 CAT patients from 12 studies
      were included: 1430 from 2 studies comparing DOACs with LMWHs, 1212 from 4
      studies comparing DOACs with VKAs and 2078 from 6 studies comparing VKAs to
      LMWHs. Recurrent VTE occurred in 4.9% of patients receiving DOACs, 9.6% receiving
      VKAs and 8.4% receiving LMWHs. The network meta-analysis showed a not significant
      increase of recurrent VTE in patients receiving LMWHs compared to those receiving
      DOACs (RR 1.3, 95% CI 0.9 to 2.0). The risk of recurrent VTE was higher in
      patients receiving VKAs compared to LMWHs (RR 1.5, 95% CI 1.0 to 2.0) or DOACs
      (RR 2.0, 95% CI 1.3 to 3.0) with no heterogeneity. Major bleeding occurred in
      4.9, 4.1 and 4.3% of patients with CAT treated with DOAC, VKA or LMWH,
      respectively. No significant differences were observed from the direct, indirect
      and network meta-analyses. CONCLUSION: In patients with CAT, DOACs showed a good
      efficacy and safety profile compared to other anticoagulants and is candidates to
      be an alternative to LMWHs.

PMID- 30196196
TI  - Enhanced photocatalytic performance of Ag/TiO2 nanohybrid sensitized by black
      phosphorus nanosheets in visible and near-infrared light.
AB  - The efficient utilization of solar energy for environmental cleaning has
      attracted great attention, where the key is to efficiently harvest the visible
      and near-infrared (NIR) light which occupies approximately 95% of the solar light
      energy. Recently, black phosphorus (BP), as a new staring 2D material, has been
      extensively studied as photocatalytic materials due to its broad light absorption
      and tunable bandgap. Herein, we report a novel ternary nanocomposite, BP-Ag/TiO2,
      prepared through controlled deposition of Ag clusters on the surface of TiO2
      nanocrystals and then incorporated to BP nanosheets. The BP-Ag/TiO2 nanocomposite
      has shown excellent photocatalytic activity towards the degradation of methylene
      blue (MB) under visible and NIR light irradiation. About 100% and even 25% of MB
      was degraded in 85 min under >420 nm and >780 nm irradiation, respectively. The
      enhanced photocatalytic activity of BP-Ag/TiO2 nanocomposite was mainly ascribed
      to the sensitization of BP nanosheets by fully harvest of solar light and high
      electron-hole separation efficiency. We believe that the BP-Ag/TiO2 nanocomposite
      will be an effective photofunctional material in full-spectrum solar energy
      conversion and opens up a new door for the development of solar light driven
      photocatalysts for the remediation of environmental pollution.

PMID- 30196197
TI  - Highly conductive, mechanically strong graphene monolith assembled by three
      dimensional printing of large graphene oxide.
AB  - The manufacturing of three-dimensional (3D) graphene monolith with high
      mechanical and electrical performance has become an urgent issue in view of their
      potential applications in energy and electronics fields. Due to the structure
      rigidity and poor liquid-phase processing capability of graphene sheets, it is
      challenging to fabricate 3D graphene monolith with high mechanical performance,
      including strength, toughness and resiliency. Graphene oxide (GO) shows an
      improved dispersibility and reduction-restorable conductivity, which enables it
      to effectively balance the processing and comprehensive performances of graphene
      monolith. Here, we demonstrate a strategy to fabricate high-performance, shape
      designable 3D graphene monolith through a 3D printing method based on large-sized
      graphene oxide (LGO) fluid ink. The concentration of the LGO ink for printing is
      as low as 20 mg/mL. The resulting monolith exhibits low density (12.8 mg/cm3),
      high electrical conductivity (41.1 S/m), high specific strength (10.7 * 103
      N.m/Kg) and compressibility (up to 80% compressive strain). Such a 3D printing
      technique enables plenty of complicated monolith structures and broadens the
      application range of graphene.

PMID- 30196198
TI  - Effect of dietary neutral detergent fibre source on lambs growth, meat quality
      and biohydrogenation intermediates.
AB  - With this trial we have tested the effects of structural and chemical composition
      of neutral detergent fibre (NDF) of the diet on lamb fatty acid composition of
      meat and subcutaneous fat. Twenty lambs, were fed complete diets with low starch
      and similar NDF content of different origin (ground alfalfa or soybean hulls).
      Animal performance and product quality were not affected by treatments. Rumen pH
      increased and parakeratosis intensity decreased with the level of alfalfa in the
      diet. Increasing the alfalfa proportion in the diet decreased t10-18:1 (P =
      .023), increased t11-18:1 (P = .003) and decreased the t10/t11 ratio according to
      a quadratic pattern (P = .020). Chemical composition and structure of the diet's
      fibrous fraction influenced the BI pattern of the final product. Forty percent of
      alfalfa in diet reduced the severity of t10-shift, but for its full resolution,
      other factors should be considered including forage particle size and buffering
      capacity of the diet.

PMID- 30196199
TI  - Age-related changes in the carcass composition and meat quality of fallow deer
      (DAMA DAMA L.).
AB  - The present study investigated the possible differences in carcass composition as
      well as texture, structure and percentage of different muscle types of the most
      valuable muscles (BF - biceps femoris, SM - semimembranosus, and L - longissimus)
      from fallow deer (Dama dama L.) bucks shot in the forest farm in north-western
      Poland at four different ages: 18, 30, 42 and 54 months. It was found that
      carcasses of young fallow deer (18-30 months), compared to older animals, were
      characterised by a higher dressing proportion, a higher percentage of the most
      valuable commercial cuts (the saddle, haunch and shoulder), high meat yield with
      the lowest percentage of bones and a lower percentage of skin and head. Their
      muscles, compared with older animals, were characterised by a lower percentage of
      red fibres, lower muscle fibre area, thinner perimysium and endomysium, lower
      amount of intramuscular fat and as a consequence lower hardness, springiness,
      cohesiveness, as well as a higher pH and lower thermal drip.

PMID- 30196200
TI  - Influence of multiple freeze-thaw cycles on quality characteristics of beef
      semimembranous muscle: With emphasis on water status and distribution by LF-NMR
      and MRI.
AB  - Influences of multiple freeze-thaw (F-T) cycles on water status and distribution,
      microstructure and physicochemical properties of beef were investigated. Low
      field nuclear magnetic resonance (LF-NMR) relaxation showed three water
      components were assigned to bound, immobilized and free water in beef matrix.
      With the increase of F-T cycles, the relaxation time and peak area of immobilized
      water decreased significantly (P < 0.05), which suggested the freedom and
      population of immobilized water decreased. T1 and T2 magnetic resonance images
      displayed a continuous decrease of water intensity in beef during multiple F-T
      cycles. The cryo-scanning electron microscopy results revealed repeated F-T
      cycles resulted in more and more large holes in the beef muscle fiber. The
      repeated F-T cycles also led to decrease of pH value, WHC, L* and a* values,
      hardness, springiness, cohesiveness and resilience, and the increase of thawing
      loss, cooking loss, b* and TBARS value. Partial least-squares regression models
      stated the potential of LF-NMR to predict the quality of beef as a non
      destructive method.

PMID- 30196201
TI  - Partial replacement of meat and fat with hydrated wheat fiber in beef burgers
      decreases caloric value without reducing the feeling of satiety after
      consumption.
AB  - The aim of this study was to evaluate the effects of different levels of hydrated
      wheat fiber replacing meat and fat in beef burgers on technological
      characteristics, sensory acceptance and hunger satisfaction. The different levels
      of hydrated wheat fiber (1 g fiber: 6 g water) were 0, 1.25, 2.5, 3.75 and 5.0 g
      of fiber/80 g burger portion. Results showed that the greater the addition of
      hydrated wheat fiber, the lower the protein (P < .0001) and lipid (P = .0006)
      content and consequently the greater the reduction in caloric value. Burgers with
      up to 3.75 g fiber/80 g portion showed the same (P > .05) sensory acceptance as
      the Control burgers (those without added fiber). Sandwiches comprised of burgers
      with 2.5 and 5.0 g fiber/80 g portion caused the same (P > .05) hunger
      satisfaction (satiety feeling) as those comprised of Control burgers for up to 3
      h after consumption. Burgers containing 3.75 g fiber/80 g burger may represent an
      interesting alternative for people who want to reduce caloric intake and/or
      increase the proportion of insoluble fiber in their diet.

PMID- 30196202
TI  - Descriptive and hedonic sensory perception of Brazilian consumers for smoked
      bacon.
AB  - The descriptive and hedonic sensory perception of bacon manufactured using
      different smoking processes was studied. Six bacon samples were evaluated: three
      manufactured with woods, two with liquid smokes, and a commercial bacon.
      Consumers rated their overall liking (OL) and responded the check-all-that-apply
      (CATA) questions coupled with ideal profile method (IPM).1 The preliminary result
      showed that LS2 and Bamboo were the best-rated bacons. However, data analysis
      indicated two segments of consumers (both n = 50), with significant differences
      in the OL. The first segment liked fatty and smoked bacons, while the second
      valued the texture and appearance. The drivers of liking in both segments were
      the attributes related to texture, juiciness and the smoky aroma. The use of
      different woods in the bacon smoking process modified the descriptive and hedonic
      sensory perception of consumers.

PMID- 30196203
TI  - Differential effects of size-specific particulate matter on emergency department
      visits for respiratory and cardiovascular diseases in Guangzhou, China.
AB  - BACKGROUND: Studies differentiating the cardiorespiratory morbidity effects of
      PM2.5, PM10, and PM2.5~10 (i.e. coarse PM or PMc) are still limited and
      inconsistent. OBJECTIVE: To estimate the acute, cumulative, and harvesting
      effects of exposure to the three size-specific PM on cardiorespiratory morbidity,
      and their concentration-response relations. METHODS: A total of 6,727,439
      emergency department (ED) visits were collected from 16 public teaching hospitals
      in Guangzhou, from January 1st 2012 to December 31st 2015, among which over 2.1
      million were asthma, COPD, pneumonia, respiratory tract infection (RTI),
      hypertension, stroke, and coronary heart disease (CHD). Distributed lag non
      linear models (DLNM) was used to estimate the associations between the three size
      specific PM and ED visits for the cardiovascular diseases. Long-term trends,
      seasonality, influenza epidemics, meteorological factors, and other gas
      pollutants, including SO2, NO2, and O3, were adjusted. We stratified the analyses
      by gender and age. RESULTS: Elevated PM2.5 and PM10 were significantly associated
      with increased ED visits for pneumonia, RTI, and CHD at both lag0 and lag0-3. A
      10 MUg/m3 increment of PMc (at lag0-14) was estimated to increase ED visits for
      pneumonia by 6.32% (95% CI, 4.19, 8.49) and for RTI by 4.72% (95% CI, 3.81,
      5.63), respectively. PMc showed stronger cumulative effects on asthma in children
      than elderly. We observed significant harvesting effects (i.e. morbidity
      displacements) of the three size-specific PM on respiratory but very little on
      cardiovascular ED visits. The concentration-response curves suggested non-linear
      relations between exposures to the three different sizes of PM and respiratory
      morbidity. CONCLUSIONS: Overall, the three size-specific PM demonstrated distinct
      acute and cumulative effects on the cardiorespiratory diseases. PM2.5 and PMc
      would have significant effects on pneumonia and RTI. Strategies should be
      considered to further reduce levels of ambient PM2.5 and PMc.

PMID- 30196204
TI  - Coal combustion residues and their effects on trace element accumulation and
      health indices of eastern mud turtles (Kinosternon subrubrum).
AB  - Coal combustion is a major energy source in the US. The solid waste product of
      coal combustion, coal combustion residue (CCR), contains potentially toxic trace
      elements. Before 1980, the US primarily disposed of CCR in aquatic settling
      basins. Animals use these basins as habitat and can be exposed to CCR,
      potentially affecting their physiology. To investigate the effects of CCR on
      eastern mud turtles (Kinosternon subrubrum), we sampled 30 turtles exposed to
      CCRs and 17 unexposed turtles captured in 2015-2016 from the Savannah River Site
      (Aiken, SC, USA). For captured turtles, we (1) quantified accumulation of CCR in
      claw and blood samples, (2) used bacterial killing assays to assess influences of
      CCR on immune responses, (3) compared hemogregarine parasite loads, and (4)
      compared metabolic rates via flow-through respirometry between CCR-exposed and
      unexposed turtles when increased temperature was introduced as an added stressor.
      Turtles exposed to CCR accumulated CCR-associated trace elements, corroborating
      previous studies. Blood Se and Sr levels and claw As, Se, and Sr levels were
      significantly higher in turtles from contaminated sites. Average bacterial
      killing efficiency was not significantly different between groups. Neither
      prevalence nor average parasite load significantly differed between CCR-exposed
      and reference turtles, although parasite load increased with turtle size.
      Regardless of site, temperature had a significant impact on turtle metabolic
      rates; as temperature increased, turtle metabolic rates increased. The effect of
      temperature on turtle metabolic rates was less pronounced for CCR-exposed
      turtles, which resulted in CCR-exposed turtles having lower metabolic rates than
      reference turtles at 30 and 35  degrees C. Our results demonstrate that turtles
      accumulate CCR from their environment and that accumulation of CCR is associated
      with changes in turtle physiological functions when additional stressors are
      present.

PMID- 30196205
TI  - A simple boronic acid-based fluorescent probe for selective detection of hydrogen
      peroxide in solutions and living cells.
AB  - An approach of high sensitivity and selectivity for hydrogen peroxide (H2O2)
      detection is highly demanded due to its important roles in regulating diverse
      biological process. In this work, we introduced an easily synthesized fluorescent
      "turn off" probe, BNBD. It is designed based on the core structure of 4-chloro-7
      nitrobenzofurazan as a fluorophore and incorporated with a specific H2O2-reactive
      group, aryl boronate, for sensitive and selective detection of H2O2. We
      demonstrated its selectivity by incubating the probe with other types of ROS, and
      measured the limit of detection of BNBD as 1.8 nM. BNBD is also conducive to H2O2
      detection at physiological conditions. We thus applied it to detect both
      exogenous and endogenous changes of H2O2 in living cells by confocal microscopy,
      supporting its future applications to selectively monitor H2O2 levels and
      identify H2O2-related physiological or pathological responses from live cells or
      tissues in the near future.

PMID- 30196206
TI  - Conjugation of antifungal benzoic acid derivatives as a path for detoxification
      in Penicillium brasilianum, an endophyte from Melia azedarach.
AB  - In this study, the consumption of 4-bromobenzoic acid and 4-chlorobenzoic acid by
      the fungus Penicillium brasilianum, an endophyte from Melia azedarach is
      evaluated. This fungus metabolizes these halobenzoic acids to produce three new
      brominated compounds, which have been isolated and characterized, and three new
      chlorinated derivatives identified by HRMS. Among these products, (4
      bromobenzoyl)proline has been also chemically synthesized and employed in
      biological assays, thus providing insights for the elucidation of the defense
      mechanism of P. brasilianum towards these halobenzoic acids.

PMID- 30196207
TI  - Discovery of Wogonin-based PROTACs against CDK9 and capable of achieving
      antitumor activity.
AB  - Wogonin is a natural product isolated from the Scutellaria baicalensis and has
      been proved to be a potent and selective inhibitor of CDK9. Using this scaffold,
      we designed and synthesized a series of proteolysis targeting chimeras (PROTACs)
      targeting CDK9 by recruiting ubiquitin E3 ligase cereblon (CRBN). For
      constructing diverse Wogonin-based PROTACs, a "click chemistry" approach was
      employed for the synthesis of CDK9-targeting PROTACs. The results of western
      blotting assays showed that compounds containing triazole group in the linker
      could selectively downregulate the intracellular CDK9 level. Among these
      compounds, 11c could selectively degrade CDK9 in a concentration-dependent
      manner. In addition, the application of the proteasome inhibitor MG132 and CRBN
      siRNA silencing confirmed that 11c could promote the proteasome-dependent and
      CRBN-dependent degradation. Consistent with the degradation of the CDK9 protein,
      11c selectively inhibits proliferation of CDK9-overexpressed cancer cells. Thus,
      our Wogonin-based PROTAC would be an efficient probe that induces the degradation
      of CDK9.

PMID- 30196208
TI  - Stereoisomeric guaiacylglycerol-beta-coniferyl aldehyde ether induces distinctive
      apoptosis by downregulation of MEK/ERK pathway in hepatocellular carcinoma cells.
AB  - Two 8-O-4'-type neolignan epimers erythro-guaiacylglycerol-beta-coniferyl
      aldehyde ether (1) and threo-guaiacylglycerol-beta-coniferyl aldehyde ether (2)
      were isolated from the stems of Picrasma quassioides. Further chiral separation
      gave two pairs of enantiomers 1a/1b and 2a/2b. The cytotoxicity assay against
      hepatocellular carcinoma Hep3B and HepG2 cells was evaluated by MTT assay. The
      results showed that 1b (IC50 = 45.56 MUM) and 2b (IC50 = 39.02 MUM) had more
      cytotoxic effect than its enantiomers 1a (IC50 = 82.66 MUM) and 2a (IC50 = 67.97
      MUM) in Hep3B cells, respectively. Moreover, 1b and 2b could induce more
      apoptotic cells as well as higher reactive oxygen species (ROS) generation than
      1a and 2a at 50 MUM. In addition, a further study on the phosphoinositide 3
      kinase (PI3K)/AKT and mitogen-activated protein kinase kinase (MEK)/extracellular
      signal-regulated kinase (ERK) signaling pathways was investigated. The results
      revealed that all compounds had no significant effect on PI3K/AKT pathway,
      however, 1b and 2b attenuated the relative levels of p-MEK and p-ERK when
      compared with 1a and 2a. Taken together, the absolute configurations of
      guaiacylglycerol-beta-coniferyl aldehyde ether had an impact on the inhibitory
      effect on Hep3B cells. The inactivation of MEK/ERK signaling pathway might
      contribute to apoptosis induction and ROS generation in 1b- and 2b-treated cells.

PMID- 30196209
TI  - A novel strategy to evaluate the quality of herbal products based on the chemical
      profiling, efficacy evaluation and pharmacokinetics.
AB  - The purpose of this study was to establish a chemical profiling method to compare
      the chemical composition of herbal products by using extracts of Belamcandae
      Rhizoma(EBR) extracted with different polarity solvent as an example, and
      evaluate the quality of EBR based on the analysis of chemical profiling, efficacy
      evaluation and pharmacokinetics. As seen from the results of chemical profiling,
      the PCA and PLS-DA score plot indicated that the dots of Belamcandae Rhizoma
      water extracts were separated from ethanol extracts obviously, which suggested
      significant differences of chemical profiling existing in the different solvent
      extracts. The PCA and PLS-DA loading plot illustrated that the main compounds
      contributing to chemical profiling differences were tectoridin(TD), iristectorin
      B(IT B), iridin(ID), tectorigenin(TG), irigenin(IG), iristectorigein A(IG A),
      dichotomitin(DT) and irisflorentin(IF). Furthermore, the results of HPLC analysis
      demonstrated that the contents of these main compounds in ethanol extracts were
      significantly higher than that in water extracts (P < 0.01). Both the
      pharmacological and hematoxylin-eosin staining studies indicated that the ethanol
      extracts of Belamcandae Rhizoma had a better therapeutic effect than water
      extracts in oral ulcer model rats (P<0.01). It is suggested that the ethanol
      extracts were beneficial to the absorption and bioavailability of TG which was
      one of the most important bioactive compounds of Belamcandae Rhizoma in
      pharmacokinetic study in rats. This work provided a novel method to optimize the
      extraction process of EBR and related herbal products. Compared with the
      conventional chemical fingerprint methodology, the approach proposed above is not
      only a powerful tool to identify efficacy-related components for the quality
      evaluation, but also can be used to predict the therapeutic efficacy of herbal
      products.

PMID- 30196210
TI  - How is biodiversity changing in response to ecological restoration in terrestrial
      ecosystems? A meta-analysis in China.
AB  - Biodiversity is an important ecosystem characteristic, and is vital for
      maintaining ecosystem health and stability. However, biodiversity was often
      ignored in previous Chinese restoration planning and design due to its complex
      roles and the unclear mechanisms in providing human well-being. In order to
      evaluate the response of biodiversity to ecological restoration in terrestrial
      ecosystems, we assembled biodiversity in different metrics and different
      organisms and generated a large dataset comprised 2099 observations from 103
      published studies to conduct a meta-analysis in China. Our results revealed that
      the biodiversity of restored ecosystem increased by 43% compared with degraded
      state, but it was difficult to recover to the natural level across the whole
      China. The gap between restored and natural ecosystems was about 13%. Ecological
      restorations have contributed not only to increasing vegetation coverage but also
      to improving soil environment and habitat quality. The recovery levels of
      vascular plant, soil microorganism and soil invertebrate were 30%, 73% and 48%,
      respectively. Biodiversity recovery would be better reflected in enhancing the
      structure feature (65%) such as plant height and density rather than the
      diversity feature (18%) such as diversity indices of Shannon and Simpson.
      Moreover, the response of biodiversity to ecological restoration varied with
      restoration actions (i.e., initial land use/cover type, restoration approach and
      restoration age), and the interaction effects among restoration actions
      significantly impacted biodiversity recovery. Passive approach performed better
      than active approach for biodiversity recovery. Meanwhile, the magnitude and
      direction of the impact of ecological restoration on biodiversity greatly altered
      with environmental conditions (i.e., climate condition and altitude). Our
      findings could facilitate priority setting and selection of treatment methods for
      biodiversity recovery during ecological restoration planning and assessment to
      ensure high effectiveness and sustainability.

PMID- 30196211
TI  - Mercury mobility and effects in the salt-marsh plant Halimione portulacoides:
      Uptake, transport, and toxicity and tolerance mechanisms.
AB  - The plant Halimione portulacoides, an abundant species widely distributed in
      temperate salt-marshes, has been previously assessed as bioindicator and
      biomonitor of mercury contamination in these ecosystems. The present study aims
      to assess uptake and distribution of total mercury (THg) and methylmercury (MMHg)
      within H. portulacoides, potential mercury release by volatilization through
      leaves, and toxicity and tolerance mechanisms by investigating plant
      photochemical responses. Stem cuttings of H. portulacoides were collected from a
      salt-marsh within the Tagus estuary natural protected area, and grown under
      hydroponic conditions. After root development, plants were exposed to 199HgCl2
      and CH3201HgCl, and sampled at specific times (0, 1, 2, 4, 24, 72, 120, 168 (7
      days) and 432 h (18 days)). After exposure, roots, stems and leaves were analysed
      for total 199Hg (T199Hg) and MM201Hg content. Photobiology parameters, namely
      efficiency and photoprotection capacity, were measured in leaves. Both THg and
      MMHg were incorporated into the plant root system, stems and leaves, with roots
      showing much higher levels of both isotope enriched spikes than the other plant
      tissues. Presence of both mercury isotopes in the stems and leaves and high
      significant correlations found between roots and stems, and stems and leaves, for
      both THg and MMHg concentrations, indicate Hg translocation between the roots and
      above-ground organs. Long-term uptake in stems and leaves, leading to higher Hg
      content, was more influenced by temperature and radiation than short-term uptake.
      However, the relatively low levels of both THg and MMHg in the aerial parts of
      the plant, which were influenced by temperature and radiation, support the
      possibility of mercury release by stems and leaves, probably via stomata
      aperture, as a way to eliminate toxic mercury. Regarding photochemical responses,
      few differences between control and exposed plants were observed, indicating high
      tolerance of this salt marsh plant to THg and MMHg.

PMID- 30196212
TI  - Assessing the effects of Awba dam sediment (Nigeria) on the steroidogenesis of
      H295R cells using different extraction methods.
AB  - In the present study, H295R human cells were used to investigate the endocrine
      disruptor potential of three different sediments extracts taken from a Nigerian
      tropical freshwater dam (Awba Dam), using three extraction methods that allowed a
      selective consideration of contaminants based on their binding affinity, which is
      mainly driven by polarity, to sediment particles. After exposure to different
      concentration of each extract, H295R cells were evaluated for the expression
      profiles of 10 steroidogenic enzyme genes and estradiol (E2) and testosterone (T)
      levels. Our results showed a comparable concentrated-related increase in the
      expression of 17beta-hsd1, 3beta-hsd2 and cyp21 in cells treated with the polar
      and non-polar extracts. The star, hmgr, cyp11b2 and 17beta-hsd4 were slightly
      decreased, in an apparent concentration-specific manner, after treatment with the
      polar extract and decreased in the non-polar treatment. The cyp11a and cyp17
      showed an opposite trend in the polar and non-polar treatments. E2 was
      significantly higher in cell treated with the non-polar extract. Elutriate
      exposure produced less pronounced variation in mRNA and hormones levels. Overall
      the extract with non-polar compounds produced the most severe effects in H295R
      cells. Thus, direct ingestion of detritus and mud from fishes and other benthonic
      organisms represent possible transfer of contaminants in the trophic web, and
      mainly account for alteration of the endocrine system previously observed in fish
      from the same study site.

PMID- 30196213
TI  - Interactions between freshwater ecosystem services and land cover changes in
      southern Bangladesh: A perspective from short-term (seasonal) and long-term (1973
      2014) scale.
AB  - We aimed to assess the long-term (1973-2014) and short-term (pre- and post
      monsoon) quantities, values and changes of freshwater ecosystem services (FES) in
      the wetland areas of Southern Bangladesh using land cover change as a proxy
      indicator. Bangladesh is a sub-tropical country that receives >80% of its annual
      rainfall during the monsoon and post-monsoon periods, between the months of June
      and November. Therefore, it could be hypothesized that the monsoon and post
      monsoon rainfalls significantly contribute to altering the local land cover, and
      consequently change the FES. Our multi-stage methodology, among others, included;
      (i) participatory FES identification (ii) long-term and seasonal land cover
      analysis using Remote Sensing and GIS, and (iii) assessing FES quantities and
      values using an expert-developed FES Matrix. The results identified 14 major FES;
      seven provisioning, six regulating and one cultural service. The results showed
      that over the last 40 years, significant land cover transformations occurred in
      the study area e.g. increase of agricultural land, rural vegetation with
      settlement (RVS) in exchange of wetlands, along with significant seasonal
      variations include increase of wetland in the post-monsoon seasons and
      agricultural land in the pre-monsoon seasons. Such changes contributed to the
      decrease of total long-term FES quantities and economic values including a
      significant reduction of regulating and provisioning services. Post-monsoon
      seasons experienced increased quantities of regulating services (e.g. soil
      fertility, water purification and biodiversity), mainly as a result of additional
      rainfall, although its overall quantities considerably decreased over the long
      term. The results of the study highlighted the importance of prudent land
      management policies at rural scales for better ecosystem services and
      conservation.

PMID- 30196214
TI  - How do households perceive flood-risk? The impact of flooding on the cost of
      accommodation in Dublin, Ireland.
AB  - Climate change and human behaviour, such as building on floodplains, are
      increasing the incidence of floods in urban areas. This paper investigates the
      relationship between flood risk and residential accommodation costs, both sales
      and rental, using a detailed dataset of over 650,000 sale and rental listings in
      Dublin, Ireland over the period 2006-2015. These are combined with detailed data
      for the Dodder river on 1% flood risk and past flooding events. Research to date
      suggested that the lack of a persistent effect may have an impact on buyers' and
      sellers' risk perceptions by changing with the prevalence of hazard events and
      that homebuyers are unaware of flood risks and insurance requirements when
      bidding on properties. Using hedonic regression techniques, the presented work
      shows opposite results: flood events are found to have a negative impact,
      particularly on sale prices, while being at 1% risk has no effect once past flood
      events are controlled for. For past flood events, however, there is evidence to
      suggest that this impacts on property values, certainly in the areas affected and
      up to 200 m away. Before the institutional flood risk maps were published, the
      assessment was based on existing Ordnance Survey maps which showed areas 'Liable
      to flooding' generated with land surveys carried out around the 1830. Set against
      these devices for raising awareness of flooding is the Irish constitution which
      regards property rights almost the same as human rights, which obvious impacts on
      the ability of planners to implement development/zoning plans. On the basis of
      this evidence, it is reasonable to conclude that households pay more attention to
      past flood events than to scientific assessments of flood risk, has important
      policy implications about communicating flood risk to consumers.

PMID- 30196215
TI  - Robust spatial analysis of sequestered metals in a Southern California Bioswale.
AB  - Bioswales are a type of permeable green infrastructure designed to slow
      stormwater and clean runoff by sequestering pollutants such as heavy metals.
      Measurements of dissolved pollutants before and after the bioswale often justify
      their ability to clean this runoff, but research addressing the physical and
      chemical sequestration of these pollutants is scarce. Soil samples were taken
      from an arid bioswale and analyzed for concentrations of aluminum, cobalt,
      chromium, copper, iron, magnesium, manganese, nickel, lead, vanadium and zinc.
      Heat maps of the concentration of these metals in soil were generated via
      Empirical Bayesian Kriging (EBK) and demonstrate that location-specific
      sequestration differs between metals within the same swale. Sequential extraction
      with a modified Tessier et al. (1979) protocol coupled with profiles of metal
      concentration versus distance along the main flow axis in the bioswale illustrate
      that the carbonate soil fraction contains elevated concentrations of zinc, lead,
      cobalt, and manganese, metals sequestered by the bioswale with statistical
      significance.

PMID- 30196216
TI  - High sulfide production induced by algae decomposition and its potential
      stimulation to phosphorus mobility in sediment.
AB  - This study is devoted to addressing the effects of algae blooms on sulfur cycle
      and the consequent phosphorus mobility in the sediments of freshwater lake
      ecosystems. A mesocosm experiment was conducted to investigate these effects
      through monitoring the dynamics of sulfur (S), iron (Fe) and phosphorus (P) in
      water and sediments, and their diffusion fluxes at the sediment-water interface
      (SWI). In addition, the abundance of sulfate-reducing bacteria (SRB) in the water
      column was also detected. The addition of the algae lead to an increase of SRB, a
      drastic decline of sulfate and a significant increase of total dissolved sulfide
      (SigmaS2-, the peak value of near 3.0 mmol/L on day 6) in the water column. These
      results suggest the sulfate reduction was dramatically promoted during algae
      decomposition. Indeed the SigmaS2- was 2 to 3 times of SO42- initial
      concentration, and higher SigmaS2- was produced with higher algal biomass.
      Moreover, the diffusive flux of SigmaS2- at the SWI was negative, indicating that
      diffusion of SigmaS2- from water column toward sediment was occurring. These
      results indicated that algae decomposition might also be another important source
      of SigmaS2- (termed "algae-derived SigmaS2-") in addition to sulfate reduction.
      The increase of Fe(II) in surface sediment pore-water was slightly delayed
      compared to the SigmaS2- generation in the water column, which illustrated that
      Fe oxyhydroxides in sediments were transformed into Fe(II) through chemical
      reduction of SigmaS2-. Concomitantly, the vertical distribution of PO43- in high
      amounts algae group suggested that desorption and release of iron oxides-bound
      PO43- occurred in sediments. Collectively, algae bloom can boost the lake
      eutrophication not only through direct release of nutrients but also through the
      high production of SigmaS2-and indirect promotion of phosphorus mobility in
      sediment.

PMID- 30196217
TI  - Retention-release of ciprofloxacin and azithromycin in biosolids and biosolids
      amended soils.
AB  - Ciprofloxacin (CIP) and azithromycin (AZ) are commonly prescribed antibiotics,
      often found at elevated concentrations in treated sewage sludge (biosolids), and
      could pose human and ecological risks when land applied. Limited retention
      release data preclude assessing potential risks from the target antibiotics in
      biosolids and biosolids-amended soils. The present work assessed sorption
      desorption of CIP and AZ in biosolids and biosolids-amended soils using the
      "traditional" batch equilibration method. The batch equilibration method also
      included un-amended soils for comparison. Release potentials of the biosolids
      borne antibiotics were assessed via multiple desorption equilibrations in the
      presence of CaCl2, soils, PbCl2, or competing antibiotic (CIP versus AZ)
      solutions. Desorption kinetics of CIP from biosolids were also evaluated by the
      diffusive gradient in thin films technique (DGT), coupled with a diffusion
      transport-exchange model available in 2D-DIFs. Sorption of both antibiotics
      followed linear models with partitioning coefficient (Kd) values for CIP ranging
      between 40 and 334 L kg-1 in soils and 357 L kg-1 in biosolids, and values for AZ
      ranging between 11 and 202 L kg-1 in soils and 428 L kg-1 in biosolids.
      Antibiotic desorption from the biosolids was highly hysteretic (hysteresis
      coefficients < 0.003) and desorption of the biosolids-borne chemicals was
      extremely small (<3%) using any of the various desorption equilibration
      approaches. Desorption was hysteric in soils too; where desorption percentages
      were 4, 5, and 26% for CIP and 6, 32, and 50% for AZ in the silt loam soil,
      manured sand, and sand, respectively. CIP release from biosolids determined by
      DGT was also small (<1%), ascribed to low dissolved and labile concentrations in
      the solid phase and a small effective diffusion coefficient. Results obtained
      using equilibrium and dynamic approaches suggest that the target antibiotic
      bioaccessibilities from biosolids and finer-textured (typical agricultural) soils
      would be minimal and that biosolids (not soils) control desorption of the two
      biosolids-borne chemicals.

PMID- 30196218
TI  - Can variability in corticosterone levels be related to POPs and OPEs in feathers
      from nestling cinereous vultures (Aegypius monachus)?
AB  - Persistent organic pollutants (POPs) are still globally distributed and some have
      been shown to interact with the endocrine system of birds. However, the
      relationship between POPs and the stress response mediated by the hypothalamic
      pituitary-adrenal (HPA) axis is still poorly understood. Raising concerns are now
      focused on the toxic properties of emergent organophosphate ester flame
      retardants (OPEs), but whether OPEs interact with the HPA axis response has not
      yet been investigated. We measured corticosterone concentrations in feathers
      (CORTf) as a long-term biomarker of the bird HPA axis response and we
      investigated their relationship with POP and OPE concentrations in down feathers
      of nestling cinereous vultures (Aegypius monachus). We also examined whether high
      contaminant burden and high CORTf concentrations impacted the duration of chick
      development. The most predominant compounds were the following: p,p'-DDE (3.28 +/
      0.26 ng g-1 dw) > gamma-HCH (0.78 +/- 0.09 ng g-1 dw) > BDE-99 (0.73 +/- 0.09 ng
      g-1 dw) > CB-153 (0.67 +/- 0.04 ng g-1 dw). The most persistent POP compounds (CB
      170, -177, -180, -183, -187, -194 and p,p'-DDE) were associated (P = 0.02) with
      high concentrations of CORTf (range: 0.55-6.09 pg mm-1), while no relationship
      was found when OPEs were tested (P > 0.05). Later egg-laying was positively
      associated to high levels of CORTf (P = 0.02) and reduced duration of chick
      development (P < 0.001), suggesting a beneficial effect of the HPA axis response
      on the growth of the chicks. In addition, males with high concentrations of the
      most persistent POP compounds tended to show a reduced duration of the nestling
      period (P = 0.05) and an equal fledging success than chicks with lower levels.
      These findings suggest that POPs, but not OPEs, may interact with the HPA axis
      response of chicks, although levels were not high enough to cause detrimental
      consequences.

PMID- 30196219
TI  - Organophosphate esters in house dust: A comparative study between Canada, Turkey
      and Egypt.
AB  - Organophosphate esters (OPEs) are commonly used as flame retardants (FRs) and
      plasticizers. The usage of OPEs has increased recently due to the ban of several
      brominated flame retardants, but information on levels in the environment,
      including the indoor environment is still limited. We investigated the occurrence
      and distribution of 12 OPEs in urban house dust from Vancouver, Canada; Istanbul,
      Turkey; and Cairo, Egypt. The median ?OPE concentration was 41.4 MUg/g in the
      Vancouver samples while median levels in Istanbul and Cairo were significantly
      lower. The median composition profiles of OPEs in Vancouver and Cairo were
      dominated by tris (2-butoxyethyl) phosphate (TBOEP), accounting for 56 and 92% of
      total OPEs respectively while it showed a detection frequency of only 14% in
      Istanbul. Tris (2-chloropropyl) phosphate (TCPP) was the most abundant
      chlorinated OPE representing 20 and 36% of the total OPEs in Vancouver and
      Istanbul respectively, but was below the detection limit in the Cairo dust
      samples. Consistent with other studies, SigmaOPE concentrations were ~1 to 2
      orders of magnitude higher than PBDEs and currently used flame retardants in the
      same dust samples. The mean estimated daily intakes (EDI) of SigmaOPE from dust
      were 115, 38 and 9 ng/kg/bw/day in Vancouver, Cairo and Istanbul respectively for
      toddlers where adults were ~10 times lower. The total toddler OPE intake ranged
      from 115 to 2900, 38 to 845 and from 9 to 240 ng/kg bw/day across the three
      cities. TBOEP had the largest contribution to the EDI in both toddler and adults,
      where toddler TBOEP exposures via dust represented 4% to 80%, 2% to 44% and 0.1%
      to 6% of the Reference Doses (RfD) in the mean and high intake scenarios for
      toddlers in Vancouver, Cairo and Istanbul respectively.

PMID- 30196220
TI  - Understanding the antagonism of Hg and Se in two shark species from Baja
      California South, Mexico.

PMID- 30196221
TI  - Enhanced inactivation of E. coli by pulsed UV-LED irradiation during water
      disinfection.
AB  - Pulsed ultraviolet (UV) irradiation has presented enhanced inactivation
      efficiency in water disinfection and food decontamination. As an emerging UV
      source, UV light-emitting diodes (UV-LEDs) are an attractive alternative for
      pulsed irradiation because they can be turned on and off with a high and
      adjustable frequency. In this study, disinfection efficiencies of pulsed and
      continuous UV-LED irradiation were compared for Escherichia coli (E. coli)
      inactivation in water using a high power 285 nm LED and low power 265 and 280 nm
      LEDs. Factors including various duty cycles, pulse frequencies and UV irradiances
      were evaluated. The log-inactivation of E. coli increased substantially as the
      duty cycle decreased from 100% to 5% at the same UV dose. For 265 and 280 nm
      LEDs, the log-inactivation enhancements of pulsed UV irradiation were similar.
      When a higher irradiance was applied, the energy efficiency enhancement of pulsed
      UV irradiation became more obvious. The log-inactivation of E. coli enhanced
      remarkably using high current pulsed irradiation of 280 nm LEDs. Compared to
      continuous UV irradiation, pulsed UV-LED irradiation is an attractive alternative
      for E. coli inactivation in water considering energy efficiency.

PMID- 30196222
TI  - Technical quality of fauna monitoring programs in the environmental impact
      assessments of large mining projects in southeastern Brazil.
AB  - Biodiversity monitoring is a key element of impact assessment follow-up
      activities, as it has the potential to generate relevant information about the
      actual impacts of approved projects on the environment. However, the
      effectiveness of such monitoring programs depends on issues such as technical
      quality. The extent to which this issue actually affects biodiversity monitoring
      is unclear. This knowledge gap was addressed in this study, whose main objective
      was to analyze the technical quality of fauna monitoring, using empirical data
      from large-scale mining enterprises in the state of Minas Gerais in southeastern
      Brazil. More specifically, this study aimed at analyzing: 1) whether license
      conditions related to fauna monitoring programs were being met by mining
      companies; 2) the extent to which fauna monitoring programs met a set of
      technical quality criteria; 3) whether there were significant differences among
      taxonomic groups; and, finally, 4) how fauna monitoring programs can be made more
      meaningful to decision-makers. A total of 236 fauna monitoring reports were
      analyzed. Findings indicated that, while companies complied with all license
      conditions, their fauna programs met, on average, 32% of the desirable technical
      requirements, and there were no significant differences among taxonomic groups.
      The main technical quality gaps were found to be lack of driving questions,
      hypothesis-testing and conceptual models, as well as lack of comparisons between
      control and impacted areas. Overall, findings indicated that the data generated
      in such programs have very limited value to decision-makers as they do not shed
      sufficient light on the actual impacts of mining activities on biodiversity. The
      study discusses a number of barriers to more meaningful fauna monitoring
      programs, and highlights the urgent need for revising current Terms of Reference.

PMID- 30196223
TI  - Climatic burden of eating at home against away-from-home: A novel Bayesian Belief
      Network model for the mechanism of eating-out in urban China.
AB  - Dietary patterns of eating away-from-home (AFH) considerably differ from those of
      eating at home in urban China, thus generating varied carbon footprints. However,
      few studies have investigated the effect of eating places on diet-related
      climatic burden, and few have modelled the mechanism under the condition of
      eating-out because the decision of consumers on whether to eat AFH or at home is
      determined by multiple non-linear socioeconomic factors. Here, we compared the
      carbon footprints of eating at home and AFH using household survey data from 12
      Chinese provinces, and developed a Bayesian Belief Network (BBN) model to
      identify key factors of eating AFH. Our findings show that eating AFH leads to
      higher climatic burdens though respondents consume less food on average than when
      eating at home. However, in urban areas, the carbon footprint generated increases
      more rapidly from eating at-home than when eating AFH. The BBN model was found to
      have strong capability to predict the possibility of eating out with an accuracy
      of 89%. Although diet patterns and embedded carbon footprint vary considerably
      across provinces from northeastern to southwestern China, sufficient evidence
      could not be found to support the influence of geographic factors on the decision
      of respondents to eat AFH at large scale. Instead, individual occupation and
      income were found to be the two key contributors. Thus, merely estimating the
      carbon footprint of food consumption is currently not sufficient, but social and
      economic elements need to be quantitatively considered to differentiate the
      eating-place effect on diet-related climatic burden.

PMID- 30196224
TI  - Nitrogen and phosphorus removal and Typha domingensis tolerance in a floating
      treatment wetland.
AB  - The aim of this work was to study the efficiency of microcosms-scale floating
      treatment wetlands (FTWs) in the N and P removal from a synthetic runoff effluent
      and to evaluate the effluent tolerance of Typha domingensis. Each FTW consisted
      of a raft constructed with a plastic net where T. domingensis plants were
      installed. In order to evaluate the plant role, reactors with FTWs and without
      FTWs (controls) were used. P and N additions were carried out as follows: 5 mg L
      1 P (P5 and P5-control); 10 mg L-1 N (N10 and N10-control); 5 mg L-1 P + 10 mg L
      1 N (P5N10 and P5N10-control). Also, a biological control (B-control) without
      contaminant addition was used. The removal of soluble reactive phosphorus and
      total phosphorus were significantly higher in the FTWs than in the controls.
      Ammonium and nitrate concentrations were not significantly different between FTWs
      and controls at the end of the experiment. However, nitrate concentrations showed
      significant differences between FTWs and controls during the experiment. N and P
      were mainly accumulated in plant tissues and not in the sediment. Plants
      tolerated the effluent conditions and showed a positive growth rate. The use of
      FTWs is a promising strategy for the sustainable treatment of water bodies
      affected by runoff waters.

PMID- 30196225
TI  - Changes in the abundance and community composition of different nitrogen cycling
      groups in response to fumigation with 1,3-dichloropropene.
AB  - The fumigant 1,3-dichloropropene (1,3-D) is widely-used to control pathogenic
      bacteria, fungi, nematodes and insects in soil before a crop is planted. Although
      fumigants in general have been reported to have a 'fertilizer effect' in the soil
      by increasing nitrogen availability, little is known of how a specific fumigant
      such as 1,3-D affects available nitrogen. This study used real-time quantitative
      PCR (qPCR) and 16S rRNA gene amplicon sequencing techniques to investigate the
      effects of 1,3-D on microorganisms involved in nitrogen cycling that were present
      in 2 soils: Jiangxi lateritic red soil and Beijing fluvo-aquic soil. The fumigant
      1,3-D temporarily decreased the abundance of 11 functional genes involved in
      nitrogen-fixing, nitrification and denitrification in both soil types. Different
      nitrogen cycling groups recovered to the unfumigated level in various incubation
      phases. Microorganisms containing nifH, nxrB, napA and qnorB genes were most
      vulnerable to 1,3-D fumigation. However, a stronger and longer inhibition effect
      of 1,3-D on these 11 functional genes was observed in Jiangxi soil than in
      Beijing soil. At the same time, the abundance of nifH, AOBamoA, nirS, qnorB and
      cnorB genes was significantly increased 59 days after 1,3-D fumigation.
      Fumigation with 1,3-D significantly reduced the nitrogen-fixing bacteria
      Azospirillum and Paenibacillus; the nitrifiers Nitrosomonas and Nitrospira; and
      the denitrifiers Pseudomonas, Paracoccus and Sphingomonas. Conversely, fumigation
      with 1,3-D increased the nitrogen-fixing bacteria Bradyrhizobium and Rhizobium;
      the nitrification bacteria Nitrosospira and Nitrolancea; and the denitrification
      bacteria Sphingobium, Alcanivorax, Bacillus, Streptomyces and Aeromonas.
      Fumigation with 1,3-D therefore caused significant shifts in the species
      composition and number of microbes directly involved in nitrogen cycling in the
      short-term. These results contribute toward a better understanding of the impact
      of 1,3-D fumigation on various types of soil nitrogen-cycling groups.

PMID- 30196226
TI  - Development of a vibrational startle response assay for screening environmental
      pollutants and drugs impairing predator avoidance.
AB  - The present paper describes the vibrational startle response assay (VSRA), a new
      robust, simple and automated in vivo medium- to high-throughput procedure for
      assessment of the escape response and its habituation in zebrafish larvae. Such
      behaviors enable fish larvae to escape from predator strikes in aquatic
      ecosystems. The assay is based on measuring the distance moved by each larva
      during the startle response evoked by repetitive vibrational stimuli. The
      iterative reduction observed in the response to a series of tapping stimulus in
      VSRA met the main criteria of habituation. Subsequently, the analysis of
      concordance using a battery of neuroactive compounds modulating different
      neurotransmitter systems demonstrated that the results of VSRA are highly
      predictive of the effects on other vertebrates. Finally, as a proof of concept,
      VSRA was used to test two relevant environmental pollutants at different
      concentrations. The results demonstrated that VSRA is suitable for concentration
      response analysis of environmental pollutants, opening the possibility to
      determine the potency and the associated hazard of impaired escape response for
      the different compounds. Therefore, we suggest that VSRA could be a valuable tool
      for screening of chemical compounds capable of compromising predator avoidance
      behavior.

PMID- 30196227
TI  - Phase-segregated Membrane Model assessed by a combined SPR-AFM Approach.
AB  - Model biomembranes can provide valuable insights into the properties of complex
      biological membranes. Among several techniques, Surface Plasmon Resonance (SPR)
      provides a label-free analysis of the interactions of bioactive molecules with
      biomembranes with an experimental setup that allows mimicking biological
      environments. Nevertheless, protocols that enable the preparation of stable
      supported membrane systems with reproducible structural and functional properties
      on the biosensor chip are still needed. In this work, we present a simple
      protocol to modify SPR substrates that allows the formation of a phase-segregated
      supported lipid bilayer (SLB). SLBs are formed by fusion of lipid vesicles of
      pure phospholipids (DMPC, DPPC and DOPC) and of a ternary mixture (DOPC/16:0
      SM/Cho in 2:1:1 molar ratio) on a SPR gold sensor chip covered with a
      dithiothreitol monolayer. The formation of a SLB on the SPR sensing surface in a
      reproducible way was assessed by the combined use of the SPR technique with AFM.
      The interaction of a cholesterol-extracting drug with SLBs was studied as a model
      of membrane-lipophilic biomolecule interaction. The proposed strategy allowed us
      to obtain a membrane model where phase coexistence is present and where Cho
      depletion from ternary mixtures was comparable to the extraction results reported
      for human erythrocytes.

PMID- 30196228
TI  - Plasmonic carbon nanohybrids for repetitive and highly localized photothermal
      cancer therapy.
AB  - Integrating metallic and non-metallic platform for cancer nanomedicine is a
      challenging task and bringing together multi-functionality of two interfaces is a
      major hurdle for biomaterial design. Herein, NIR light responsive advanced hybrid
      plasmonic carbon nanomaterials are synthesized, and their properties toward
      repetitive and highly localized photothermal cancer therapy are well understood.
      Graphene oxide nanosheets having thickness of ~2 nm are synthesized using
      modified Hummers' method, thereafter functionalized with biodegradable NIR light
      responsive gold deposited plasmonic polylactic-co-glycolic acid nanoshells
      (AuPLGA NS, tuned at 808 nm) and NIR dye (IR780) to examine their repetitive and
      localized therapeutic efficacy as well resulting side effects to nearby healthy
      cells. It is observed that AuPLGA NS decorated graphene oxide nanosheets (GO
      AuPLGA) and IR780 loaded graphene oxide nanosheets (GO-IR780) are capable in
      standalone complete photothermal ablation of cancer cells within 4 min. of 808 nm
      NIR laser irradiation and also without the aid of any anticancer drugs. However,
      GO-AuPLGA having the potential for repetitive photothermal treatment of a big
      tumor, ablate the cancer cells in highly localized fashion, without having side
      effects on neighboring healthy cells.

PMID- 30196229
TI  - Harnessing carbazole based small molecules for the synthesis of the fluorescent
      gold nanoparticles: A unified experimental and theoretical approach to understand
      the mechanism of synthesis.
AB  - Six structurally different carbazoles (1-6) were explored as the green reducing
      agents for the synthesis of the fluorescent Au nanoparticles with tailor-made
      morphology in anionic (sodium dodecyl sulphate, SDS), cationic
      (cetyltrimethylammonium bromide, CTAB) and neutral (polyvinylpyrrolidone, PVP)
      micelle medium. Structure of the carbazoles played an important role in
      controlling the morphology, rate of formation and fluorescent activity of the Au
      nanoparticles. The Au nanoparticles formed in-situ also simultaneously catalyzed
      the intermolecular CC and NN couplings between the carbazoles, leading to the
      corresponding bis-carbazole derivatives. The free and bis-carbazole derivatives
      functionalized the surface of the synthesized Au nanoparticles and thereby
      controlling their morphology and fluorescence activity. A computational study was
      also made to determine the origin of the absorption and emission bands of the
      synthesized nanoparticles. The combined experimental and theoretical studies
      unraveled the nanoparticle formation process and mechanistic pathway of this
      green and easily implementable synthetic protocol of Au nanoparticles.

PMID- 30196230
TI  - Understanding the antimicrobial activity of water soluble gamma
      cyclodextrin/alamethicin complex.
AB  - In our previous investigation (Zhang et. al., J. Functional Foods 40 (2018) 700
      706), we have proposed a method of complexation of alamethicin (ALM) with gamma
      cyclodextrin (gamma-CD) to increase the solubility and demonstrated an
      enhancement in its antimicrobial activity against Listeria monocytogenes. In this
      study, transmission electron microscopy of L. monocytogenes treated with gamma
      CD/ALM complex indicated cell lysis due to pore formation. This was further
      corroborated by fluorescent dye leakage from DMPC/cholesterol liposomes when
      exposed to gamma-CD/ALM complex for molar ratios of 1, 5 and 10. The extent of
      dye leakage increased with ALM-lipid ratio in the range of 0.00015 to 0.16. Dye
      leakage of gamma-CD/ALM complex was found to be the highest for molar ratio of 5,
      consistent with our earlier results of antimicrobial activity of the complex
      against L. monocytogenes. All atom molecular dynamics (MD) simulation showed that
      gamma-CD/ALM complex can effectively bind to the 3:1 POPE/POPG bilayer, a mimic
      of bacterial cell membrane. In addition, circular dichroism spectrum indicated
      that ALM in the complex has a helical conformation in solution as well as in the
      presence of liposome. Transmembrane MD simulation of six gamma-CD/ALM complex
      aggregates in alpha helical conformation showed water channel with barrel stave
      like pore structure.

PMID- 30196231
TI  - Deformation of giant unilamellar vesicles under osmotic stress.
AB  - Biological membrane plays an important role in maintaining an osmotic equilibrium
      between the cytoplasm and the extracellular solution of cells. Here, the giant
      unilamellar vesicles (GUVs) as cell models were used to investigate the effect of
      osmotic stress on phospholipid membranes. The deformation of GUVs, including
      inward budding and outward budding, was systematically investigated by the
      osmotic press from glucose, sucrose, LiCl, and KCl solutions. The permeability
      (P) of DMPC, DMPC/10 mol% Chol GUVs, DMPC/25 mol% Chol GUVs, and DMPC/40 mol%
      Chol GUVs in glucose, sucrose, LiCl, and KCl solutions were all obtained. The P
      value decreases with the addition of more cholesterol in the bilayer. The
      monovalent cations caused higher permeability of lipid bilayer membranes due to
      their combination with phospholipids. The molar flux of water (J) value was found
      to be the key factor for determining the deformation state from mainly inward
      budding to mainly outward budding. The findings in this paper may help us to
      understand cell transformation triggered with osmotic stress.

PMID- 30196232
TI  - The therapeutic effects of lipoxin A4 during treadmill exercise on monosodium
      iodoacetate-induced osteoarthritis in rats.
AB  - Lipoxin A4 (LXA4), a kind of adipokines, is a potent stop signal of inflammation.
      Our preliminary study found that LXA4 of serum and intra-articular lavage fluid
      (IALF) was rapidly elevated in 2 h and rapidly reduced to normal level at 4 h
      after moderate-intensity treadmill exercise. The aim was to confirm the
      therapeutic effects of LXA4 during treadmill exercise on rat model of monosodium
      iodoacetate (MIA)-induced OA and the detailed mechanism of LXA4 on OA. One
      hundred and twenty-four male Sprague-Dawley rats were submitted to two different
      protocols. A single session of treadmill exercise: sixty-four rats were randomly
      divided into treadmill exercise of different intensities for 60 min only once (n
      = 4). Formal treadmill exercise: sixty rats were randomly divided into six groups
      (n = 10): control group (CG), knee OA group (OAG), OA with treadmill exercise of
      different intensities (OAL, OAM and OAH), and OAM + BOC-2 (an antagonist of LXA4
      receptor). The rats were evaluated by ELISA, histology, immunohistochemistry and
      western blotting. Fibroblast-like synoviocytes (FLSs) were obtained from knee
      joint of rats. The effects of LXA4 on interleukin (IL)-1beta induced FLSs were
      evaluated by western blotting and immunofluorescence. The results of ELISA,
      histological evaluation, western blotting and immunohistochemistry indicated that
      OAM had a better treatment which could be suppressed by BOC-2. Moreover, LXA4
      could attenuate the expression of matrix metalloproteinase (MMP)-3 and MMP-13 and
      suppress the expression of nuclear factor-kappa B (NF-kappaB) p65 induced by IL
      1beta in FLSs. The therapeutic effects of LXA4 during treadmill exercise on MIA
      induced OA via inhibiting NF-kappaB signaling pathway.

PMID- 30196233
TI  - Revealing the protective and pathogenic potential of MAIT cells.
AB  - Mucosal-associated Invariant T (MAIT) cells represent a large proportion of T
      cells in human blood, and are also present throughout the body, being
      concentrated at mucosal sites. Their high level of conservation throughout
      mammalian evolution and recognition of conserved microbial antigens, derived from
      precursors of riboflavin (vitamin B2) biosynthesis, suggest an important role in
      protective immunity to pathogens. However, the picture that is emerging of MAIT
      cell immune function is increasingly complex, with numerous correlations of MAIT
      cell numbers with human diseases, and with recent studies demonstrating their
      pathogenic potential. The conditions that drive MAIT cell responses towards a
      protective versus pathogenic role are only beginning to be deciphered and, yet,
      must be understood for any attempt to harness MAIT cells therapeutically. In this
      review we summarise our current knowledge of immune protection and pathology
      driven by MAIT cells, models used to study their role in immunity and steps
      towards elucidating the immune signals driving these responses.

PMID- 30196234
TI  - Biological function of SPNS2: From zebrafish to human.
AB  - Sphingosine-1-phosphate (S1P), a bioactive metabolite of sphingolipid, has an
      important role in lymphocyte trafficking, immune responses, vascular and
      embryonic development, cancer, bone homeostasis, etc. S1P is produced
      intracellularly and then secreted into the circulation to engage in the above
      physiological or pathological processes by regulating the proliferation,
      differentiation and survival of target cells; however, the underlying mechanisms
      of S1P secretion and function remain poorly understood. Recently, Spinster 2
      (SPNS2), a newly identified transporter of S1P, was shown to act as a mediator of
      intracellular S1P release and play an important role in the regulation of S1P. In
      this review, we focus on the primary biological characteristics and functions of
      SPNS2 and provide novel insights into the development of therapies for S1P
      related disorders.

PMID- 30196235
TI  - Disorganized and unresolved states in adulthood.
AB  - Fear plays a central role in attachment theory and disorganization in adulthood.
      Fear associated with traumatic memories interferes with resolution of trauma
      resulting in disorganized mental states, captured as unresolved/disorganized
      speech surrounding loss and/or abuse in the Adult Attachment Interview. Mothers
      who are unresolved experience fear stemming from traumatic memories and display
      frightening behavior towards their infants. Disorganization can predispose
      individuals to dissociative mental processes, including altered states
      (absorption), PTSD, and depersonalization. Social psychologists have
      conceptualized adult disorganization as fear of the romantic partner. Studies
      examining stability of adult disorganization indicate unresolved loss is more
      readily resolved than unresolved abuse. Understanding disorganization in
      adulthood, including experiences that support reparation and reorganization, is
      important for developing effective interventions.

PMID- 30196236
TI  - The Mutant p53-Targeting Compound APR-246 Induces ROS-Modulating Genes in Breast
      Cancer Cells.
AB  - TP53 is the most frequently mutated gene in human cancer and thus an attractive
      target for novel cancer therapy. Several compounds that can reactive mutant p53
      protein have been identified. APR-246 is currently being tested in a phase II
      clinical trial in high-grade serous ovarian cancer. We have used RNA-seq analysis
      to study the effects of APR-246 on gene expression in human breast cancer cell
      lines. Although the effect of APR-246 on gene expression was largely cell line
      dependent, six genes were upregulated across all three cell lines studied, i.e.,
      TRIM16, SLC7A11, TXNRD1, SRXN1, LOC344887, and SLC7A11-AS1. We did not detect
      upregulation of canonical p53 target genes such as CDKN1A (p21), 14-3-3sigma,
      BBC3 (PUMA), and PMAIP1 (NOXA) by RNA-seq, but these genes were induced according
      to analysis by qPCR. Gene ontology analysis showed that APR-246 induced changes
      in pathways such as response to oxidative stress, gene expression, cell
      proliferation, response to nitrosative stress, and the glutathione biosynthesis
      process. Our results are consistent with the dual action of APR-246, i.e.,
      reactivation of mutant p53 and modulation of redox activity. SLC7A11, TRIM16,
      TXNRD1, and SRXN1 are potential new pharmacodynamic biomarkers for assessing the
      response to APR-246 in both preclinical and clinical studies.

PMID- 30196238
TI  - Survival Impact of Delaying Postoperative Radiotherapy in Patients with
      Esophageal Cancer.
AB  - The purpose of the current study was to retrospectively assess the effect of
      postoperative radiotherapy (RT) delay on survival for patients with esophageal
      cancer. From 2008 to 2011, patients with esophageal cancer who had undergone
      postoperative RT in five different hospitals in China were reviewed. Clinical
      data, including time interval between surgery to RT, were prospectively
      collected. Kaplan-Meier method was conducted to estimate the effect of each
      variable on progression-free survival (PFS) and overall survival (OS), with
      differences assessed by log-rank test. Univariate Cox proportional-hazards models
      were performed for both PFS and OS for all assumed predictor variables.
      Statistically significant predictor variables (P < .05) on univariate analysis
      were then included in multivariate Cox proportional-hazards models, which were
      performed to compare the effects of RT delay on PFS and OS. A total of 316
      patients were finally enrolled in this prospectively multicentric study. Time to
      RT after surgery varied from 12 days to over 60 days (median, 26 days).
      Multivariate analysis showed that delay to RT longer than the median does not
      appear to be a survival cost. There was also no statistically difference in PFS
      (P = .513) or OS (P = .236) between patients stratified by quartiles (<=21 days
      vs ?35 days). However, patients with particularly long delays (?42 days)
      demonstrated a detrimental impact on OS (P = .021) but not PFS (P = .580).
      Delaying postoperative RT of esophageal cancer does not impact PFS, but results
      in a significant reduction on OS if delaying longer than 6 weeks.

PMID- 30196237
TI  - Autophagy: A New Mechanism of Prosurvival and Drug Resistance in Multiple
      Myeloma.
AB  - Autophagy is an intracellular self-degradative process that balances cell energy
      source and regulates tissue homeostasis. In physiological condition, autophagy
      funnels cytoplasmic constituents to autophagolysosomes for degradation and is an
      alternative way for cell-death behavior. Here, we inspected autophagy as a
      prosurvival mechanism essential for drug resistance in multiple myeloma (MM).
      Accordingly, autophagy inhibitors used in association to conventional anti-MM
      drugs might enforce the effect against resistant MM plasma cells and render
      autophagy a new therapeutic target.

PMID- 30196239
TI  - Short-Term Responders of Non-Small Cell Lung Cancer Patients to EGFR Tyrosine
      Kinase Inhibitors Display High Prevalence of TP53 Mutations and Primary
      Resistance Mechanisms.
AB  - Non-small cell lung cancer (NSCLC) with activating EGFR mutations in exon 19 and
      21 typically responds to EGFR tyrosine kinase inhibitors (TKI); however, for some
      patients, responses last only a few months. The underlying mechanisms of such
      short responses have not been fully elucidated. Here, we sequenced the genomes of
      16 short-term responders (SR) that had progression-free survival (PFS) of less
      than 6 months on the first-generation EGFR TKI and compared them to 12 long-term
      responders (LR) that had more than 24 months of PFS. All patients were diagnosed
      with advanced lung adenocarcinoma and harbored EGFR 19del or L858R mutations
      before treatment. Paired tumor samples collected before treatment and after
      relapse (or at the last follow-up) were subjected to targeted next-generation
      sequencing of 416 cancer-related genes. SR patients were significantly younger
      than LR patients (P < .001). Collectively, 88% of SR patients had TP53 variations
      compared to 13% of LR patients (P < .001). Additionally, 37.5% of SR patients
      carried EGFR amplifications compared to 8% of LR patients. Other potential
      primary resistance factors were also identified in the pretreatment samples of 12
      SR patients (75%), including PTEN loss; BIM deletion polymorphism; and
      amplifications of EGFR, ERBB2, MET, HRAS, and AKT2. Comparatively, only three LR
      patients (25%) were detected with EGFR or AKT1 amplifications that could possibly
      exert resistance. The diverse preexisting resistance mechanisms in SR patients
      revealed the complexity of defining treatment strategies even for EGFR-sensitive
      mutations.

PMID- 30196240
TI  - Tetrazole-functionalized cation-exchange membrane adsorbers with high binding
      capacity and unique separation feature for protein.
AB  - The modification with high-density functional groups is a widely used method to
      enhance the binding capacity of membrane adsorbers, where the types of the
      attached groups are crucial to achieve good selectivity for protein separation.
      In this work, a novel tetrazole-functionalized weak cation-exchange membrane with
      high-capacity was prepared by constructing tetrazole-containing polymer brushes
      on the surface of regenerated cellulose membrane via the combination of surface
      initiated atom transfer radical polymerization (SI-ATRP) and "click chemistry"
      between cyano and azide. Densities of tetrazolyl groups on the membranes can be
      easily controlled by manipulating the polymerization time. The binding capacity
      of lysozyme increased with the polymerization time but eventually reached maximum
      due to the reduction of the utilization percentage of ion-exchange sites. The
      adsorption of newly designed membrane conforms to the feature of weak cation
      exchanger in terms of pH and salt effects, whereas the effect of pH exhibits a
      large difference from that on the carboxylic-functionalized ion-exchange
      membranes. Most importantly, the membranes possess higher dynamic binding
      capacity independent of the flow rate of mobile phase compared with the
      previously reported cation-exchange membranes. Featured with the unique
      properties, the modified membrane could simultaneously purify lysozyme and
      ovotransferrin from hen egg white at higher productivity. The present work
      provides a new alternative for membrane chromatography of biomacromolecules.

PMID- 30196241
TI  - Four new choanoflagellate species from extreme saline environments: Indication
      for isolation-driven speciation exemplified by highly adapted Craspedida from
      salt flats in the Atacama Desert (Northern Chile).
AB  - With this study we aim to extend the knowledge on the biogeography of craspedid
      choanoflagellates with additional data from extreme environments. Up to now, very
      little is known about choanoflagellates from extreme saline environments, as most
      studies have focused on marine and freshwater habitats. Though previously
      investigated high saline ice biota communities have indicated a possible
      adaptation to environments with high salt concentrations. Hypersaline endorheic
      basins, so-called salt flats or salares from the Atacama Desert in Northern Chile
      provide an intense environment regarding fluctuating and extreme salinities,
      which allow for studies on evolutionary adaptations of protists to hypersaline
      conditions. This study focused on choanoflagellate species isolated from
      different salt flats, their morphological characteristics using light and
      electron microscopy, molecular marker genes (SSU and LSU rDNA) and their salinity
      tolerance. Here, we described four new craspedid choanoflagellate species, highly
      adapted to the hypersaline environment of the Atacama Desert. This study extends
      our knowledge on choanoflagellate phylogeny and ecology and can become the basis
      for further molecular studies to understand the mechanisms of adaptations.
      Additionally, we emphasize the need of adding additional data such as
      autecological characteristics to amend species definitions, which is only
      possible from cultivated strains. This data would support the use of molecular
      data originating from metagenomic analyses also in an ecological context.

PMID- 30196242
TI  - A critical review on the impacts of beta-glucans on gut microbiota and human
      health.
AB  - The beta-glucans are the glucose polymers present in the cells walls of yeast,
      fungi and cereals. beta-Glucans are the major compositions of various nutritional
      diets such as oats, barley, seaweeds and mushrooms. Various biological activities
      of beta-glucans have been reported such as anticancer, antidiabetic, anti
      inflammatory and immune-modulating effects. The importance of beta-glucans in
      food processing industries such as bread preparation, yogurt and pasta have been
      well elucidated. In recent findings on food science research gut microbiota plays
      a significant role and vastly studied for its intermediate role in regulating
      health. Several reports have suggested that beta-glucans should have a
      significant impact on the gut microbiota changes and in turn on human health. The
      review was aimed to accumulate the evidence on types of beta-glucans, their
      functional properties and the mechanism by how the beta-glucans regulate the gut
      microbiota and human health. The various in vitro, in vivo and clinical studies,
      have been summarized, in particular, the changes happening upon the beta-glucans
      supplementation on the gut microbiota. Overall, this review updates the recent
      studies on beta-glucans and gut microbiota and also inputs the demanding
      questions to be addressed in beta-glucans-microbiota research in the future.

PMID- 30196243
TI  - Gut microbes as future therapeutics in treating inflammatory and infectious
      diseases: Lessons from recent findings.
AB  - The human gut microbiota has been the interest of extensive research in recent
      years and our knowledge on using the potential capacity of these microbes are
      growing rapidly. Microorganisms colonized throughout the gastrointestinal tract
      of human are coevolved through symbiotic relationship and can influence
      physiology, metabolism, nutrition and immune functions of an individual. The gut
      microbes are directly involved in conferring protection against pathogen
      colonization by inducing direct killing, competing with nutrients and enhancing
      the response of the gut-associated immune repertoire. Damage in the microbiome
      (dysbiosis) is linked with several life-threatening outcomes viz. inflammatory
      bowel disease, cancer, obesity, allergy, and auto-immune disorders. Therefore,
      the manipulation of human gut microbiota came out as a potential choice for
      therapeutic intervention of the several human diseases. Herein, we review
      significant studies emphasizing the influence of the gut microbiota on the
      regulation of host responses in combating infectious and inflammatory diseases
      alongside describing the promises of gut microbes as future therapeutics.

PMID- 30196244
TI  - N gene enhances resistance to Chilli veinal mottle virus and hypersensitivity to
      salt stress in tobacco.
AB  - Plants use multiple mechanisms to fight against pathogen infection. One of the
      major mechanisms involves the disease resistance (R) gene, which specifically
      mediates plant defense. Recent studies have shown that R genes have broad
      spectrum effects in response to various stresses. N gene is the resistance gene
      specifically resistant to Tobacco mosaic virus (TMV). However, the role of N gene
      in abiotic stress and other viral responses remains obscure. In this study, we
      investigated the mechanisms by which N regulates plant defense responses under
      Chilli veinal mottle virus (ChiVMV) infection and salt stress. Here, we monitored
      the physiological and molecular changes of tobacco plants under virus attack. The
      results showed that when tobaccoNN and tobacconn plants were exposed to ChiVMV,
      tobaccoNN plants displayed higher susceptibility at five days post infection
      (dpi), while tobacconn plants exhibited higher susceptibility at 20 dpi. In
      addition, accumulation of reactive oxygen species (ROS) and expression of HARPIN
      INDUCED1(NtHIN1) were higher in tobaccoNN plants than in tobacconn plants at 5
      dpi. Interestingly, the pathogenesis-related gene (NtPR1 and NtPR5), the
      activities of antioxidant enzymes, and the content of salicylic acid (SA) in
      tobaccoNN plants increased compared with those in tobacconn plants. It was
      suggested that the N gene induced a hypersensitive response (HR) and enhanced the
      systemic resistance of plants in response to ChiVMV via the SA-dependent
      signaling pathway. In addition, the N gene was also induced significantly by salt
      stress. However, tobaccoNN plants showed hypersensitivity toward increased salt
      stress, and this hypersensitivity was dependent on abscisic acid and jasmonic
      acid but not SA. Taken together, our results indicate that the N gene appears to
      be important in the plant response to ChiVMV infection and salt stress.

PMID- 30196245
TI  - RNA-Seq-based transcriptome profiling and expression of 16 cytochrome P450 genes
      in the benzo[alpha]pyrene-exposed estuarine copepod Eurytemora affinis.
AB  - The calanoid copepod Eurytemora affinis is one of the most abundant estuarine
      species and is considered to be an ideal candidate species for ecotoxicological
      research. An RNA-Seq-based transcriptome was developed from whole bodies of this
      species. Among 142,442 contigs of the de novo assembly by Trinity, 48,480 open
      reading frame (ORF) contigs were found using TransDecoder. A total of 17,762
      genes were identified by BLAST analysis, which covers about 75% of the annotated
      genes in the E. affinis genome. Kyoto Encyclopedia of Genes and Genomes (KEGG)
      pathway analysis showed that most annotated sequences were related to metabolism
      pathways, including xenobiotic biodegradation. Using transcriptome data, we
      identified putative transcripts related to xenobiotic processing genes including
      phase I enzymes, phase II enzymes, transporters, and transcription factors. To
      understand the CYP-mediated detoxification metabolism of xenobiotics, we measured
      the transcriptional levels of 16 CYPs (within full sequences) of E. affinis in
      response to benzo[alpha]pyrene (B[alpha]P). Most Ea-CYP genes were significantly
      down- and/or up-regulated (P < 0.05) in response to B[alpha]P, suggesting that Ea
      CYP genes are likely involved in detoxification (mainly in biotransformation of
      xenobiotics) with particular genes, demonstrating significant upregulation or
      downregulation compared to others, as shown in other copepod model species (e.g.
      Tigriopus japonicus and Paracyclopina nana). This study will provide insight into
      the potential role of E. affinis in response to various toxic or xenobiotic
      chemicals in the marine environment.

PMID- 30196246
TI  - UV effect on the cathodo- and thermoluminescence properties of a gem-quality Cr
      rich diaspore (alpha-AlOOH).
AB  - This work reports on the cathodoluminescence (CL) and thermoluminescence (TL)
      properties of gem-quality diaspore samples from Milas/Mugla (Turkey) after 100 h
      of ultraviolet-C (UVC) exposure. The UVC exposure induces significant changes in
      the intensity of the CL emission in the range of 400-800 nm that would be mainly
      associated with photo-oxidation processes of the impurities (Cr3+, Ti3+, Fe2+)
      that substitute for Al3+ in the diaspore (alpha-AlOOH) lattice. The UVC effect on
      the 400 nm-TL behavior of beta irradiated samples in the range of 0.1-8 Gy
      modifies the TL glow curves probably due to both photo-transfer process where
      electrons release from deeper to shallower traps and redox reactions involving,
      also, breakages-linkages of chemical bonds. Meanwhile, the 'as received' samples
      consist of three maxima centered at about 120, 180, and 234  degrees C, the 100 h
      UVC-irradiated samples display three maxima at 122, 220 and 270  degrees C. The
      physical trapping parameters (intensity and peak position, trap depth and pre
      exponential factor) for each TL curve were estimated by using a computerized glow
      curve analysis program.

PMID- 30196247
TI  - L-[S-methyl-11C]methionine - An example of radiosynthetic optimization.
AB  - Radiosynthetic optimization is crucial in routine PET production but is often
      neglected in literature. Small changes in the radiochemical procedure can
      increase the yield significantly and reduce time fluctuation within the synthetic
      procedure enabling better planning and product release on time. Therefore, a
      highly reproducible production method for L-[S-methyl-11C]methionine is
      presented, which uses a fully automated GE TRACERlab FX C Pro synthesizer.
      Evolution of the synthetic procedure lead to a protocol with a nearly doubled
      absolute yield.

PMID- 30196248
TI  - Automated spectra analysis of in situ radioactivity measurements in the marine
      environment using NaI(Tl) detector.
AB  - The NaI(Tl) detector has become the main way of research and application of in
      situ radioactivity measurement in the marine environment due to many advantages
      on detection efficiency, power consumption, cost and applicability. But for the
      poor energy resolution and there is a high background in the low energy region of
      the spectrum measured mainly originating from the Compton scattering of natural
      radionuclides such as 40K with high concentrations in seawater, it is difficult
      and also an interesting topic for NaI(Tl) detector to identificate the
      radionuclides and calculate them in seawater by analyzing the spectra measured.
      In this paper, an in situ NaI(Tl) detector developed for the marine environment
      was energy, resolution and efficiency calibrated. The detection response matrix
      was calculated by taking all the responsible processes and interactions of gamma
      rays in water as well as in the detector into account using Monte Carlo
      simulation method. And then an improved Richardson-Lucy (R-L) deconvolution
      algorithm was proposed to reconstruct the gamma spectrum measured in the seawater
      to remove as efficiently as possible the background counts into the corresponding
      photopeaks. The original spectrum was transformed from poor energy resolution to
      the corresponding deconvolution spectrum of the high energy resolution with
      several isolated photopeaks. The experiments of synthetic spectrum and measured
      spectrum both showed promising results for the radionuclide qualitative and
      quantitative analysis.

PMID- 30196249
TI  - Radiological evaluation of the use of clay brick and pumice brick as a structural
      building material.
AB  - In this study, clay brick (CBRICK) and pumice brick (PBRICK) samples used as
      structural material in the construction of dwellings, schools, workplaces and
      factories in Turkey were compared with each other from a radiological viewpoint.
      The activity concentrations of 226Ra, 232Th and 40K naturally occurring in CBRICK
      and PBRICK samples collected from different regions of Turkey were determined by
      using a gamma-ray spectrometer with a high purity germanium detector (HPGe). The
      average activity concentrations of 226Ra, 232Th and 40K in CBRICK and PBRICK
      samples were found as 35.4 +/- 3.3, 37.5 +/- 2.4 and 593.7 +/- 42.7 Bq kg-1 and
      81.9 +/- 2.5, 65.8 +/- 6.0 and 1066.0 +/- 46.6 Bq kg-1, respectively. The radon
      surface exhalation rate (EXS) and radon mass exhalation rate (EXM) of CBRICK and
      PBRICK samples were measured by using an active radon gas analyzer with an
      accumulation container. The average value of EXS and EXM of CBRICK and PBRICK
      samples found as 45.9 +/- 2.9 mBq m-2 h-1 and 3.7 +/- 2.9 mBq kg-1 h-1 and 100.9
      +/- 4.7 mBq m-2 h-1 and 9.9 +/- 0.5 mBq kg-1 h-1, respectively. Radiological
      parameters related to external and internal exposure to members of the public
      such as the radiation protection index, alpha index, and indoor absorbed gamma
      radiation dose rate and the corresponding annual effective dose from external
      exposure, annual effective dose from inhalation of radon, and the lifetime cancer
      risk were estimated for CBRICK and PBRICK samples. The results were compared with
      each other and with the international recommended limits or criteria. The results
      reveal that the average values measured and estimated for CBRICK samples are
      approximately two times lower than those measured and estimated for PBRICK
      samples. Thus, from the radiological viewpoint, clay brick is preferable to
      pumice brick as a structural material in the building sector.

PMID- 30196250
TI  - Anticholinergic drug use and cognitive performances in middle age: findings from
      the CONSTANCES cohort.
AB  - BACKGROUND: Previous studies have shown associations between the use of
      anticholinergics (AC) and cognitive performance in the elderly, considering AC as
      a homogeneous set of drugs. The present study aims to assess the relationship
      between exposure to AC drugs and cognitive performance in middle-aged adults
      according to AC potency and drug class. METHODS: Our cross-sectional study used
      baseline data of 34 267 participants aged 45-70 from the Consultants des centres
      d'examen de sante de la securite sociale (CONSTANCES) cohort. The cumulative
      exposure to AC was measured using national reimbursement databases over the 3
      year period preceding assessment of cognitive performance. Eight classes of AC
      drugs were differentiated. Episodic verbal memory, language abilities and
      executive functions were evaluated by validated neuropsychological tests.
      Analyses were controlled on lifestyle and health status variables. RESULTS: This
      study showed a negative association between overall cumulative AC exposure and
      cognitive performances after adjustment. The use of drugs with possible AC effect
      according to the Anticholinergic Cognitive Burden scale (ACB-1 score) was only
      associated with executive functions. Analyses of AC exposure across drug classes
      showed a negative association between the use of AC antipsychotics and all
      cognitive functions assessed. Heterogeneous associations were found for the use
      of AC anxiolytics, AC opioids and AC drugs targeting the gastrointestinal tract
      or metabolism. We did not find significant associations between the use of
      antihistamines, antidepressants, cardiovascular system or other AC medications
      and cognitive function. CONCLUSION: Association between AC drugs and cognitive
      performance was highly heterogeneous across drug classes; this heterogeneity will
      have to be considered by future studies.

PMID- 30196251
TI  - Patient with ALS with a novel TBK1 mutation, widespread brain involvement,
      behaviour changes and metabolic dysfunction.

PMID- 30196252
TI  - X linked Charcot-Marie-Tooth disease and multiple sclerosis: emerging evidence
      for an association.
AB  - OBJECTIVE: X linked Charcot-Marie-Tooth disease (CMTX) is a hereditary neuropathy
      caused by mutations in GJB1 coding for connexin-32, a gap junction protein
      expressed in Schwann cells, but also found in oligodendrocytes. Four patients
      with CMTX developing central nervous system (CNS) demyelination compatible with
      multiple sclerosis (MS) have been individually published. We presently sought to
      systematically investigate the relationship between CMTX and MS. METHODS: Over 20
      years, 70 consecutive patients (36 men) with GJB1 mutations were identified at
      our Neurogenetics Unit, Athens, Greece, and assessed for clinical features
      suggestive of MS. Additionally, 18 patients with CMTX without CNS symptoms and 18
      matched controls underwent brain MRI to investigate incidental findings. Serum
      from patients with CMTX and MS was tested for CNS immunoreactivity. RESULTS: We
      identified three patients with CMTX who developed clinical features suggestive of
      inflammatory CNS demyelination fulfilling MS diagnostic criteria. The resulting
      20-year MS incidence (4.3%) differed significantly from the highest background 20
      year MS incidence ever reported from Greece (p=0.00039). The search for
      incidental brain MRI findings identified two CMTX cases (11%) with lesions
      suggestive of focal demyelination compared with 0 control. Moreover, 10 cases in
      the CMTX cohort had hyperintensity in the splenium of the corpus callosum
      compared with 0 control (p=0.0002). No specific CNS-reactive humoral factors were
      identified in patients with CMTX and MS. CONCLUSIONS: We have demonstrated a
      higher than expected frequency of MS in patients with CMTX and identified
      incidental focal demyelinating lesions on brain MRI in patients with CMTX without
      CNS symptoms. This provides circumstantial evidence for GJB1 mutations acting as
      a possible MS risk factor.

PMID- 30196253
TI  - Septicaemia in an adolescent presenting with potentially fatal CA MRSA
      osteomyelitis.

PMID- 30196254
TI  - Recurrent giant cell tumour of the maxillary sinus and pterygoid process treated
      with denosumab.
AB  - We report the case of a 74-year-old man with a giant cell tumour (GCT) of the
      right maxilla and pterygoid process. The patient presented to the maxillofacial
      and head and neck surgery clinic with an ulcerated lesion of the hard palate.
      Initial workup with CT revealed a mass within the right maxillary sinus and
      pterygoid process with associated bone expansion and erosion. Biopsy showed a GCT
      with mucosal ulceration. Two years after surgical resection, a follow-up CT
      revealed tumour recurrence involving the right pterygoid process and lateral
      pterygoid muscle. The patient was then proposed for therapy with denosumab. Under
      denosumab treatment, the lesion maintained stable dimensions and became sclerotic
      and heavily ossified.

PMID- 30196255
TI  - Venous thromboembolism leading to diagnosis of de novo malignancy in an organ
      transplant recipient.
AB  - We report the case of a patient with remote orthotopic liver transplant who was
      ultimately diagnosed with Merkel cell carcinoma following admission for initial
      venous thromboembolism. Additionally, we review pertinent literature related to
      the risk of skin cancer in solid organ transplant recipients and discuss the
      importance of yearly skin exams in this patient population.

PMID- 30196256
TI  - Recurrent gallstone ileus in a patient with ileostomy successfully treated by
      removal of impacted gallstone via the stoma.
AB  - A 75-year-old man with a permanent ileostomy presented with recurrent gallstone
      ileus that was treated successfully with removal of the stones via the stoma.

PMID- 30196257
TI  - Effect of halo-type frontal cockpit protection on overtaking.
AB  - In 2018, the Federation Internationale de l'Automobile introduced the halo
      frontal cockpit protection system into Formula 1. While extensive testing was
      conducted to confirm that the halo protects the driver from contact, the halo's
      effect on the driver during overtaking was not tested prior to its introduction.
      Here, we describe the effect of a halo-type structure on the neck muscle activity
      of one of the authors, a national-level amateur racing driver, during on-track
      simulations designed to practise overtaking. We found that the halo-type
      structure caused an increase in the rates of fatigue and workloads of
      sternocleidomastoid and cervical erector spinae. The results suggest that the
      driver adopted a forward and right laterally flexed head position, presumably to
      clear the central pillar from his visible field. This has the potential to
      increase compressive loading of the cervical spine and affect the ability to use
      visual cues during steering manoeuvres.

PMID- 30196258
TI  - Neuroblastoma with flat genomic profile: a question of representativity?
AB  - Neuroblastoma is one of the most common paediatric malignancies. Detection of
      somatic genetic alterations in this tumour is instrumental for its risk
      stratification and treatment. On the other hand, an absence of detected
      chromosomal imbalances in neuroblastoma biopsies is difficult to interpret
      because it is unclear whether this situation truly reflects the tumour genome or
      if it is due to suboptimal sampling. We here present a neuroblastoma in the left
      adrenal of a newborn. The tumour was subjected to single-nucleotide polymorphism
      array analysis of five tumour regions with >80% tumour cells in histological
      mirror sections. This revealed no aberrations compared with a normal reference
      sample from the patient. Whole exome sequencing identified two single-nucleotide
      variants present in most tumour regions, corroborating that the tumour resulted
      from monoclonal expansion. Our data provide proof-of-principle that rare cases of
      neuroblastoma can have a normal whole genome copy number and allelic profile.

PMID- 30196259
TI  - Neuromyelitis optica spectrum disorder presenting in an octogenarian.
AB  - This case describes an 81-year-old woman with a history of Sjogren's syndrome
      presenting with recurrent falls and poor balance. She subsequently developed new
      and rapidly evolving neurology including hyperaesthesia, spastic paraplegia and
      sphincteric dysfunction. Following serial clinical reviews and detailed
      investigations, MRI (brainstem and cervicothoracic spine) and a seropositive
      result for aquaporin 4 IgG, a diagnosis of neuromyelitis optica spectrum disorder
      (NMOSD) was made. This case describes the clinical course of this index patient
      with an unusual late age of onset. The report also includes a discussion on
      NMOSD. We review aspects of terminology, brief epidemiology, pathogenesis,
      notable autoimmune associations, variance in clinical presentation and current
      diagnostic criteria. We also review the importance of distinguishing NMOSD from
      multiple sclerosis in view of the significant implications for treatment and
      prognosis.

PMID- 30196261
TI  - Adjuvant conundrum in central mucoepidermoid carcinoma of the mandible: case
      presentation and literature review.
AB  - The cornerstone modality of treatment of central mucoepidermoid carcinoma (CMEC)
      of the mandible is surgery, optimally, an en bloc resection with/without
      segmental or hemimandibulectomy. Notwithstanding the documentation of a survival
      benefit in few case reports with the addition of postoperative radiotherapy in
      carefully selected high-risk patients, there does not exist a clearly defined
      consensus regarding the role of adjuvant radiotherapy. We report the case of a 49
      year-old man who presented with right lower jaw swelling which on imaging was
      found to be a multiloculated lesion causing bony expansion and cortical
      destruction of the mandible and was diagnosed with CMEC after radiological and
      histopathological criteria were met. He underwent right hemimandibulectomy and
      histopathology showed squamous and mucinous cells with positive mucicarmine
      staining and characteristic immunohistochemistry markers confirming the diagnosis
      of CMEC. He subsequently underwent adjuvant radiotherapy and is disease free 5
      years since treatment completion.

PMID- 30196260
TI  - Long-term survival in a patient with pulmonary spindle cell carcinoma treated
      with traditional Chinese medicine.
AB  - Spindle cell carcinoma (SCC) is a rare pulmonary malignancy, accounting for only
      0.2%-0.3% of all lung cancers. Therefore, the prognosis and treatment of
      pulmonary SCC is unclear. There are only 13 reported cases in literature, only
      three of which had a survival of more than 11 months. Here we reported a long
      term survival of a patient with pulmonary SCC who underwent treatment with
      traditional Chinese medicine. At the most recent follow-up in July 2018, her
      survival after diagnosis is 48 months and she continues to do well. To our
      knowledge, this is the longest survival of late stage SCC with the largest tumour
      burden.

PMID- 30196262
TI  - Goitre, lymphoma and the doughnut sign.

PMID- 30196263
TI  - Unusual cause for small bowel obstruction.

PMID- 30196264
TI  - Intractable vomiting and the medulla: neuromyelitis optica spectrum disorder
      presenting as area postrema syndrome.

PMID- 30196265
TI  - Effectiveness of service models and organisational structures supporting
      tuberculosis identification and management in hard-to-reach populations in
      countries of low and medium tuberculosis incidence: a systematic review.
AB  - OBJECTIVE: To determine which service models and organisational structures are
      effective and cost-effective for delivering tuberculosis (TB) services to hard-to
      reach populations. DESIGN: Embase and MEDLINE (1990-2017) were searched in order
      to update and extend the 2011 systematic review commissioned by National
      Institute for Health and Care Excellence (NICE), discussing interventions
      targeting service models and organisational structures for the identification and
      management of TB in hard-to-reach populations. The NICE and Cochrane
      Collaboration standards were followed. SETTING: European Union, European Economic
      Area, European Union candidate countries and Organisation for Economic Co
      operation and Development countries. PARTICIPANTS: Hard-to-reach populations,
      including migrants, homeless people, drug users, prisoners, sex workers, people
      living with HIV and children within vulnerable and hard-to-reach populations.
      PRIMARY AND SECONDARY OUTCOME MEASURES: Effectiveness and cost-effectiveness of
      the interventions. RESULTS: From the 19 720 citations found, five new studies
      were identified, in addition to the six discussed in the NICE review. Community
      health workers from the same migrant community, street teams and peers improved
      TB screening uptake by providing health education, promoting TB screening and
      organising contact tracing. Mobile TB clinics, specialised TB clinics and
      improved cooperation between healthcare services can be effective at identifying
      and treating active TB cases and are likely to be cost-effective. No difference
      in treatment outcome was detected when directly observed therapy was delivered at
      a health clinic or at a convenient location in the community. CONCLUSIONS:
      Although evidence is limited due to the lack of high-quality studies,
      interventions using peers and community health workers, mobile TB services,
      specialised TB clinics and improved cooperation between health services can be
      effective to control TB in hard-to-reach populations. Future studies should
      evaluate the (cost-)effectiveness of interventions on TB identification and
      management in hard-to-reach populations and countries should be urged to publish
      the outcomes of their TB control systems. PROSPERO REGISTRATION NUMBER:
      CRD42015017865.

PMID- 30196266
TI  - Incidence and characteristics of ventilator-associated pneumonia in a regional
      non-tertiary Australian intensive care unit: protocol for a retrospective
      clinical audit study.
AB  - INTRODUCTION: Ventilator-associated pneumonia (VAP) is a medical complication
      associated with prolonged mechanical ventilation. Most studies looking at VAP
      originate from major, tertiary intensive care units (ICUs). Our understanding of
      VAP in regional hospitals is limited. Given that patient characteristics often
      differ between metropolitan and regional centres, it is important to investigate
      VAP in a regional non-tertiary ICU. This project will establish and report the
      incidence, case characteristics and outcomes including mortality and length of
      stay related to VAP in a regional non-tertiary Australian ICU. Furthermore, it
      will compare the incidence of VAP in accordance with consultant diagnosed cases
      in the medical record, and by a post hoc screening of all cases against a list of
      previously published diagnostic criteria. METHODS AND ANALYSIS: This
      retrospective clinical audit study will screen medical records from the period 1
      January 2013 to 31 December 2016. All cases requiring mechanical ventilation for
      >=72 hours will be screened against previously reported diagnostic criteria for
      VAP. At the same time, their medical records will be screened for a documented
      diagnosis of VAP. ETHICS AND DISSEMINATION: This study has been granted ethical
      approval from the Central Queensland Hospital and Health Service (CQHHS) Human
      Research Ethics Committee (HREC/17/QCQ/11) and the Central Queensland University
      Human Research Ethics Committee (H17/05-102). This study will be submitted for
      publication in a peer-reviewed scientific journal and presented at internal
      workshops (within Queensland Health) and national and/or international scientific
      conferences.

PMID- 30196267
TI  - Universal, school-based interventions to promote mental and emotional well-being:
      what is being done in the UK and does it work? A systematic review.
AB  - OBJECTIVES: The present review aimed to assess the quality, content and evidence
      of efficacy of universally delivered (to all pupils aged 5-16 years), school
      based, mental health interventions designed to promote mental health/well-being
      and resilience, using a validated outcome measure and provided within the UK in
      order to inform UK schools-based well-being implementation. DESIGN: A systematic
      review of published literature set within UK mainstream school settings. DATA
      SOURCES: Embase, CINAHL, MEDLINE, PsycINFO, PsychArticles, ASSIA and
      Psychological and Behavioural Sciences published between 2000 and April 2016.
      ELIGIBILITY CRITERIA: Published in English; universal interventions that aimed to
      improve mental health/emotional well-being in a mainstream school environment;
      school pupils were the direct recipients of the intervention; pre-post design
      utilised allowing comparison using a validated outcome measure. DATA EXTRACTION
      AND SYNTHESIS: 12 studies were identified including RCTs and non-controlled pre
      post designs (5 primary school based, 7 secondary school based). A narrative
      synthesis was applied with study quality check. 1 RESULTS: Effectiveness of
      school-based universal interventions was found to be neutral or small with more
      positive effects found for poorer quality studies and those based in primary
      schools (pupils aged 9-12 years). Studies varied widely in their use of measures
      and study design. Only four studies were rated 'excellent' quality.
      Methodological issues such as small sample size, varying course fidelity and lack
      of randomisation reduced overall study quality. Where there were several positive
      outcomes, effect sizes were small, and methodological issues rendered many
      results to be interpreted with caution. Overall, results suggested a trend
      whereby higher quality studies reported less positive effects. The only study
      that conducted a health economic analysis suggested the intervention was not cost
      effective. CONCLUSIONS: The current evidence suggests there are neutral to small
      effects of universal, school-based interventions in the UK that aim to promote
      emotional or mental well-being or the prevention of mental health difficulties.
      Robust, long-term methodologies need to be pursued ensuring adequate recording of
      fidelity, the use of validated measures sensitive to mechanisms of change,
      reporting of those lost to follow-up and any adverse effects. Further high
      quality and large-scale research is required across the UK in order to robustly
      test any long-term benefits for pupils or on the wider educational or health
      system.

PMID- 30196268
TI  - Impact of levothyroxine therapy on obstetric, neonatal and childhood outcomes in
      women with subclinical hypothyroidism diagnosed in pregnancy: a systematic review
      and meta-analysis of randomised controlled trials.
AB  - OBJECTIVE: To determine in women with subclinical hypothyroidism diagnosed in
      pregnancy whether levothyroxine treatment compared with control, impacts
      important obstetrical or childhood outcomes (specifically IQ) in randomised
      controlled trials. DESIGN: Systematic review and meta-analysis. STUDY ELIGIBILITY
      CRITERIA: Randomised trials which met all the following were included: (1)
      reported original data of women with subclinical hypothyroidism diagnosed in
      pregnancy (by any prespecified study definition); (2) randomised to either
      levothyroxine or control (placebo or no treatment); (3) reported obstetrical
      outcomes and/or childhood neurodevelopmental outcomes and (4) published from 1980
      to January 2018 in either English or French language. DATA SOURCES: Medline,
      EMBASE, CINAHL, Cochrane Database of Systematic Reviews, Cochrane Central
      Register of Controlled Trials and ClinicalTrials.gov. OUTCOME MEASURES:
      Obstetrical, neonatal and childhood outcomes including: miscarriage, gestational
      hypertension, pre-eclampsia, preterm delivery, mode of delivery, neonatal
      intensive care unit admission, birth weight, gestational age at delivery,
      childhood IQ and neurodevelopmental scores. Risk of bias assessment Cochrane Risk
      of Bias Tool (Modified) for Quality Assessment of Randomised Controlled Trials
      RESULTS: Three trials of low to unclear risk of bias with 1837 participants were
      included. Two studies were meta-analysed for maternal and neonatal outcomes and
      two studies for childhood IQ. No statistically significant differences were found
      for any clinical outcomes with levothyroxine therapy compared with control.
      LIMITATIONS: Only three trials were identified for inclusion. CONCLUSIONS: This
      review, based on three randomised trials in women with subclinical hypothyroidism
      diagnosed in pregnancy, found no evidence of benefit of levothyroxine therapy on
      obstetrical, neonatal, childhood IQ or neurodevelopmental outcomes. Current trial
      evidence does not support the treatment of subclinical hypothyroidism diagnosed
      in pregnancy. PROSPERO REGISTRATION NUMBER: CRD4201707980.

PMID- 30196269
TI  - Systematic review of high-cost patients' characteristics and healthcare
      utilisation.
AB  - OBJECTIVES: To investigate the characteristics and healthcare utilisation of high
      cost patients and to compare high-cost patients across payers and countries.
      DESIGN: Systematic review. DATA SOURCES: PubMed and Embase databases were
      searched until 30 October 2017. ELIGIBILITY CRITERIA AND OUTCOMES: Our final
      search was built on three themes: 'high-cost', 'patients', and 'cost' and 'cost
      analysis'. We included articles that reported characteristics and utilisation of
      the top-X% (eg, top-5% and top-10%) patients of costs of a given population.
      Analyses were limited to studies that covered a broad range of services, across
      the continuum of care. Andersen's behavioural model was used to categorise
      characteristics and determinants into predisposing, enabling and need
      characteristics. RESULTS: The studies pointed to a high prevalence of multiple
      (chronic) conditions to explain high-cost patients' utilisation. Besides, we
      found a high prevalence of mental illness across all studies and a prevalence
      higher than 30% in US Medicaid and total population studies. Furthermore, we
      found that high costs were associated with increasing age but that still more
      than halve of high-cost patients were younger than 65 years. High costs were
      associated with higher incomes in the USA but with lower incomes elsewhere.
      Preventable spending was estimated at maximally 10% of spending. The top-10%, top
      5% and top-1% high-cost patients accounted for respectively 68%, 55% and 24% of
      costs within a given year. Spending persistency varied between 24% and 48%.
      Finally, we found that no more than 30% of high-cost patients are in their last
      year of life. CONCLUSIONS: High-cost patients make up the sickest and most
      complex populations, and their high utilisation is primarily explained by high
      levels of chronic and mental illness. High-cost patients are diverse populations
      and vary across payer types and countries. Tailored interventions are needed to
      meet the needs of high-cost patients and to avoid waste of scarce resources.

PMID- 30196270
TI  - Protocol for a randomised controlled trial of interventions to promote adoption
      and maintenance of physical activity in adults with mental illness.
AB  - INTRODUCTION: Physical activity (PA) has diverse benefits for physical and mental
      health and can reduce symptoms of mental illness. Adults with mental illness face
      practical, psychosocial and socioeconomic barriers to adopting and maintaining
      PA, and it is unclear how to effectively promote PA in this group. Supervised
      exercise interventions provide high support but may not promote autonomous
      motivation, which is important for PA maintenance. The aim of this study is to
      compare the effectiveness of two interventions to promote PA in adults with
      mental illness. METHODS AND ANALYSIS: This is a randomised controlled trial of
      two interventions to promote PA: (1) supervised exercise and gym membership and
      (2) motivational discussions and self-monitoring of PA using fitness trackers.
      The intervention duration is 16 weeks, including 8 weeks of weekly supervised
      group sessions, and 8 weeks of access to the gym or fitness tracker unsupervised.
      Participants are community-dwelling adults recruited from outpatient clinics of
      public mental health services. The primary outcome is PA adoption assessed using
      GENEActiv accelerometers worn continuously over 8 weeks. Secondary outcomes
      measured at baseline, postintervention (8 weeks) and follow-up (16 weeks),
      include exercise motivation, psychological distress and self-reported PA assessed
      using self-administered questionnaires and indicators of physical health measured
      by a researcher blinded to allocation (blood pressure, weight, waist
      circumference, 6 min walk test). Participant experiences will be assessed using
      qualitative focus groups with analysis informed by a theoretical model of
      behaviour (COM-B). ETHICS AND DISSEMINATION: Ethics approval has been obtained
      from the Royal Brisbane and Women's Hospital (HREC/17/QRBW/302). We plan to
      submit a manuscript on protocol development from pilot work, and a manuscript of
      the results to a peer-reviewed journal. Results will be presented at conferences,
      community and consumer forums and hospital grand rounds. TRIAL REGISTRATION
      NUMBER: ACTRN12617001017314; Pre-results.

PMID- 30196271
TI  - Chronic ocular hypertension in rabbits induced by limbal buckling.
AB  - AIM: To establish a rabbit model of chronic ocular hypertension (OHT) by limbal
      buckling. METHODS: Eighteen New Zealand White rabbits were involved and divided
      into three groups. A latex encircling band of 20, 25 or 35 mm was implanted
      behind the limbus in the right eye of each animal. The intraocular pressure (IOP)
      was monitored for 8 weeks, after which optic nerve damage was evaluated by fundus
      photography, optical coherence tomography (OCT) retrograde labelling and
      histology. Meanwhile, the anterior chamber angle (ACA) was examined by OCT and
      gonioscopy. RESULTS: OHT was induced in all animals after surgery. The IOP peaked
      at 38.0+/-3.7, 32.0+/-3.9 and 24.1+/-6.5 mm Hg in groups 1, 2 and 3,
      respectively, and remained elevated for 22, 25 and 39 days on average,
      respectively. The elevated IOPs showed good consistency within 2 weeks, although
      the durations of high IOP varied moderately. The area ratio between the optic cup
      and disc (cup to disc area) was increased in 73% of the treated eyes, and the
      average changes were 0.10+/-0.13, 0.11+/-0.08 and 0.09+/-0.02 in groups 1, 2 and
      3, respectively. The depth of the optic cup was also increased in the treated
      eyes, and the density of the retinal ganglion cells was reduced. Additionally,
      the ACA showed a dynamic change with IOP after the latter was reduced by
      paracentesis. CONCLUSION: Limbal buckling provides an effective method of
      producing chronic OHT and glaucomatous optic neuropathy in rabbits.

PMID- 30196272
TI  - Active cytomegalovirus retinitis after the start of antiretroviral therapy.
AB  - Patients with AIDS-related cytomegalovirus (CMV) retinitis receiving combined
      antiretroviral therapy (cART), but not specific anti-CMV therapy, consistently
      showed active retinitis for several months. Delayed diagnosis and treatment of
      CMV retinitis may have severe consequences. Patients first entering care with
      advanced HIV infection and vulnerability to reactivation of latent CMV infection
      should be screened immediately for CMV retinitis by dilated indirect
      ophthalmoscopy and treated with specific anti-CMV therapy without delay, in
      addition to cART.

PMID- 30196273
TI  - Microscopic examination of Gram-stained smears for anogenital gonorrhoea in men
      who have sex with men is cost-effective: evidence from a modelling study.
AB  - OBJECTIVE: To assess the cost-effectiveness of three testing strategies with or
      without light microscopic Gram-stained smear (GSS) evaluation for the detection
      of anogenital gonorrhoea among men who have sex with men (MSM) at the Amsterdam
      STI clinic using a healthcare payer perspective. METHODS: Three testing
      strategies for MSM were compared: (1) GSS in symptomatic MSM only (currently
      practised strategy), (2) no GSS and (3) GSS in symptomatic and asymptomatic MSM.
      The three testing protocols include testing with nucleic acid amplification test
      to verify the GSS results in (1) and (3), or as the only test in (2). A
      transmission model was employed to calculate the influence of the testing
      strategies on the prevalence of anogenital gonorrhoea over 10 years. An economic
      model combined cost data on medical consultations, tests and treatment and
      utility data to estimate the number of epididymitis cases and quality-adjusted
      life years (QALY) associated with gonorrhoea. Incremental cost-effectiveness
      ratios (ICERs) for the testing scenarios were estimated. Uncertainty and
      sensitivity analyses were performed. RESULTS: No GSS testing compared with GSS in
      symptomatic MSM only (current strategy) resulted in nine extra epididymitis cases
      (95% uncertainty interval (UI): 2-22), 72 QALYs lost (95% UI: 59-187) and ?7300
      additional costs (95% UI: -?185 000 (i.e.cost-saving) to ?407 000) over 10 years.
      GSS testing in both symptomatic and asymptomatic MSM compared with GSS in
      symptomatic MSM only resulted in one prevented epididymitis case (95% UI: 0-2),
      1.1 QALY gained (95% UI: 0.1-3.3), ?148 000 additional costs (95% UI: ?86 000 to
      ?217 000) and an ICER of ?177 000 (95% UI: ?67 000-to ?705 000) per QALY gained
      over 10 years. The results were robust in sensitivity analyses. CONCLUSIONS: GSS
      for symptomatic MSM only is cost-effective compared with no GSS for MSM and with
      GSS for both symptomatic and asymptomatic MSM.

PMID- 30196274
TI  - Assessors' and trainees' perceptions of workplace-based assessments in
      histopathology.
AB  - AIM: Workplace-based assessments (WBAs) are an integral part of specialist
      medical and dental training in the UK. Histopathology represents a very different
      training environment to the surgical specialities so it is important to know that
      the current WBAs are fit for purpose. A literature search revealed very little
      evidence regarding the perception of WBAs in histopathology. The aim of this
      study was therefore to assess the current perception of WBAs in histopathology by
      assessors and trainees. METHODS: A questionnaire was sent to all histopathology
      assessors and trainees on the Royal College of Pathologists database. Data were
      analysed using basic descriptive statistics. Free text comments were analysed by
      thematic analysis. RESULTS: The questionnaire was completed by 242/2175 assessors
      (response rate 11.1%) and 91/519 trainees (response rate 17.5%). There was no
      significantly different perception of WBAs between trainers and trainees
      (p>0.05). Key findings included respondents stating that they strongly disagreed
      or disagreed WBAs identify diagnostic competence (68% of trainees; 62% of
      assessors), identify trainees in difficulty (69% of trainees; 64% of assessors)
      or accurately reflect trainee progress (62% of trainees; 59% of assessors).
      Analysis of free text comments identified three main issues related to WBAs:
      their utilisation, purpose and design. CONCLUSION: There was an overall negative
      perception of WBAs, particularly their perceived regulatory nature. It appears
      that the current WBAs do not always meet the criteria of a useful test in that
      they are perceived as being applied variably, produce results with questionable
      validity and have little apparent educational value.

PMID- 30196275
TI  - Treatment of post-traumatic joint contracture in a rabbit model using pulsed,
      high intensity laser and ultrasound.
AB  - Post-traumatic joint contracture induced by scar tissues following a surgery or
      injury can leave patients in a permanent state of pain and disability, which is
      difficult to resolve by current treatments. This randomized controlled trial
      examines the therapeutic effect of pulsed high-intensity laser (PHIL) and pulsed
      high-intensity focused ultrasound (PHIFU) for post-traumatic joint contracture
      due to arthrofibrosis. The peak power levels of both PHIL and PHIFU are much
      higher than that of laser or ultrasound currently used in physical therapy, while
      short pulses are utilized to prevent damage. To test the effectiveness of these
      treatments, a rabbit knee model for joint contracture was established. Twenty-one
      rabbits were split into four groups: untreated control (n  =  5), PHIL (n  =  5),
      PHIFU (n  =  5), and a PHIL  +  PHIFU group (n  =  6). Maximum extension of the
      surgically modified rabbit knee was compared to that of the contralateral control
      knee over the course of 16 weeks. The rabbits in the untreated control group
      maintained a relatively consistent level of joint contracture, while every rabbit
      in each of the treatment groups had improved range of motion, eventually leading
      to a restoration of normal joint extension. Average recovery time was 7.6  +/- 
      1.5 weeks for the PHIL treatment group, 9.8  +/-  3.7 weeks for the PHIFU group,
      and 8.0  +/-  2.2 weeks for the combined treatment group. Histopathology
      demonstrated reduced density and accelerated resorption of scar tissues in the
      treated knee joints. This study provides evidence that both PHIL and PHIFU are
      effective in treating post-traumatic joint contracture in rabbits and warrant
      further investigation into the underlying mechanisms to optimize PHIL and PHIFU
      based treatments in a larger number of animals.

PMID- 30196276
TI  - Quantification of temporal resolution improvement factor in SMART-RECON based
      time-resolved C-arm Cone beam computed tomography angiography (TR-CBCTA).
AB  - In a recently published paper by Li et al (2018 Phys. Med. Biol. 63 075001),
      reconstruction parameters were optimized for the so-called synchronized
      multiArtifact reduction with tomographic reconstruction (SMART-RECON) method to
      enable time-resolved Cone beam computed tomography angiography (TR-CBCTA) from a
      single short-scan CBCT data set. However, the paper did not quantitatively
      address how much temporal resolution can be improved by using the SMART-RECON
      algorithm in TR-CBCTA. The purpose of this note was to present a method to
      quantify this temporal resolution improvement factor and to use that method to
      quantify the improvement in temporal resolution using SMART-RECON and optimized
      reconstruction parameters. In the method proposed in this note, the potential
      temporal blurring caused by SMART-RECON was modeled as a convolution between a
      temporal Gaussian blurring kernel and the ground truth temporal enhancement
      curve. The width parameter of the resulting Gaussian blurring kernel was used as
      a surrogate metric for temporal resolution to quantify the achievable temporal
      resolution for the conventional filtered backprojection (FBP) and SMART-RECON
      methods. The ratio of the surrogate temporal resolutions for the two
      reconstruction methods was calculated to quantify the factor of temporal
      resolution improvement. The quantitative results show that the temporal
      resolution is improved by a factor of 4.5 using SMART-RECON compared with FBP.

PMID- 30196277
TI  - Administration of Interleukin-35-Conditioned Autologous Tolerogenic Dendritic
      Cells Prolong Allograft Survival After Heart Transplantation.
AB  - BACKGROUND/AIMS: IL-35, a powerful suppressor of inflammation and autoimmunity,
      is primarily secreted by regulatory T cells (Tregs) and can, in turn, promote
      Treg differentiation. However, the precise effect of IL-35 on dendritic cells
      (DCs) remains to be clarified. METHODS: In this study, we investigated the
      expression of IL-35 in DCs after stimulation with LPS utilizing enzyme linked
      immunosorbent assay(ELISA), quantitative real-time reverse transcriptase
      polymerase chain reaction (qRT-PCR) and western blotting, and the influence of IL
      35 on the maturation and function of DCs by mixed lymphocyte reaction assay and
      flow cytometry. We further examined the regulation of IL-35 in DCs by the
      microRNA let-7i (let-7i) via transfected with let-7i mimic, inhibitor or
      suppressor of cytokine signalling 1 (SOCS1) siRNA. IL-35-overexpressing DCs were
      transfused into BALB/c recipients with C57BL/6 heart transplantations to verify
      the role of immune tolerance in transplantation. RESULTS: The results showed that
      IL-35 expression was significantly up-regulated following lipopolysaccharide
      (LPS)-induced DC maturation. Overexpression of IL-35 suppressed DC maturation,
      promoted the secretion of anti-inflammatory cytokines, and subsequently affected
      the balance between Treg and Th17 cells. IL-35 expression in DCs was regulated by
      let-7i, which targets SOCS1. The transfusion of IL-35-transfected DCs induced
      Treg generation in mice and prolonged cardiac allograft survival. CONCLUSION: Our
      data demonstrated that IL-35 induces tolerogenic DCs which are capable of
      alleviating allograft rejection. Clinical application of IL-35-treated DCs might
      be a promising approach for eliciting cardiac allograft immune tolerance.

PMID- 30196278
TI  - Protective Effects of 2-Dodecyl-6-Methoxycyclohexa-2,5 -Diene-1,4-Dione Isolated
      from Averrhoa Carambola L. (Oxalidaceae) Roots on Neuron Apoptosis and Memory
      Deficits in Alzheimer's Disease.
AB  - BACKGROUND/AIMS: The roots of Averrhoa carambola L. (Oxalidaceae) have long been
      used as a traditional Chinese medicine for the treatment of headaches, vomiting,
      coughing and hangovers. 2-dodecyl-6-methoxycyclohexa-2, 5-1, 4-dione (DMDD) has
      been isolated from A. carambola L. roots, and this study was carried out to
      investigate the potential beneficial effects of DMDD on neuron apoptosis and
      memory deficits in Alzheimer's disease. METHODS: The effects of a DMDD on
      learning and memory in APP/PS1 transgenic AD mice in vivo were investigated via
      Morris water maze and Y-type electric maze tests. In vitro, Cell viability was
      assessed by CCK-8. Apoptosis was assessed by Annexin V-FITC/PI flow cytometry
      assay, and transmission electron microscopy assay. Relative quantitative real
      time PCR and Western blot were used to determine the expressions of genes and
      proteins. RESULTS: The spatial learning and memory deficit, fear memory deficit,
      as well as apoptosis and loss of neuron in hippocampal area of APP/PS1 mice were
      reversed by DMDD in APP/PS1 transgenic AD mice. DMDD protected against the Abeta1
      42-induced apoptosis, loss of mitochondria membrane potential, induction of pro
      apoptotic Bcl-2 family protein Bax, reduction of anti-apoptotic Bcl-2 family
      proteins Bcl-2, and activation of Caspase-3, and -9 in PC-12 cells. The Bcl-2/Bax
      ratio was also increased in DMDD-pretreated PC-12 cells in vitro and APP/PS1 mice
      in vivo. CONCLUSION: DMDD has potential benefit on treating learning and memory
      deficit in APP/PS1 transgenic AD mice, and its effects may be associated with
      reversing the apoptosis of neuron via inhibiting Bax/Bcl-2 mediated mitochondrial
      membrane potential loss.

PMID- 30196279
TI  - Minimal Reporting Standards for Active Middle Ear Hearing Implants.
AB  - There is currently no standardized method for reporting audiological, surgical
      and subjective outcome measures in clinical trials with active middle ear
      implants (AMEIs). It is often difficult to compare studies due to data
      incompatibility and to perform meta-analyses across different centres is almost
      impossible. A committee of ENT and audiological experts from Germany, Austria and
      Switzerland decided to address this issue by developing new minimal standards for
      reporting the outcomes of AMEI clinical trials. The consensus presented here aims
      to provide a recommendation to enable better inter-study comparability.

PMID- 30196280
TI  - Propofol Anesthesia Precludes LFP-Based Functional Mapping of Pallidum during DBS
      Implantation.
AB  - BACKGROUND/AIMS: There are reports that microelectrode recording (MER) can be
      performed under certain anesthetized conditions for functional confirmation of
      the optimal deep brain stimulation (DBS) target. However, it is generally
      accepted that anesthesia affects MER. Due to a potential role of local field
      potentials (LFPs) in DBS functional mapping, we characterized the effect of
      propofol on globus pallidus interna (GPi) and externa (GPe) LFPs in Parkinson
      disease (PD) patients. METHODS: We collected LFPs in 12 awake and anesthetized PD
      patients undergoing DBS implantation. Spectral power of beta (13-35 Hz) and high
      frequency oscillations (HFOs: 200-300 Hz) was compared across the pallidum.
      RESULTS: Propofol suppressed GPi power by > 20 Hz while increasing power at lower
      frequencies. A similar power shift was observed in GPe; however, power in the
      high beta range (20-35 Hz) increased with propofol. Before anesthesia both beta
      and HFO activity were significantly greater at the GPi (chi2 = 20.63 and chi2 =
      48.81, p < 0.0001). However, during anesthesia, we found no significant
      difference across the pallidum (chi2 = 0.47, p = 0.79, and chi2 = 4.11, p =
      0.12). CONCLUSION: GPi and GPe are distinguishable using LFP spectral profiles in
      the awake condition. Propofol obliterates this spectral differentiation.
      Therefore, LFP spectra cannot be relied upon in the propofol-anesthetized state
      for functional mapping during DBS implantation.

PMID- 30196281
TI  - Inhibition of the Notch Signaling Pathway Reduces the Differentiation of Hepatic
      Progenitor Cells into Cholangiocytes in Biliary Atresia.
AB  - BACKGROUND/AIMS: Viral infections, especially with rotavirus, are often
      considered an initiator of the pathogenesis of biliary atresia (BA). However, the
      mechanism by which rotavirus induces BA is still unclear. METHODS: A BA mouse
      model was induced in newborn mice by i.p. inoculation with rhesus rotavirus
      within 6 h of birth. The expression of Notch pathway-associated molecules (JAG1,
      JAG2, Notch1, Notch2, Notch3, Notch4, DII1, DII3, and DII4) was measured by
      quantitative PCR and western blot analysis. Bile duct obstruction was detected by
      hematoxylin and eosin staining and CK-19 immunohistochemical staining. DAPT was
      used to inhibit the Notch pathway in vivo and in vitro. RESULTS: In the livers of
      patients with BA and rotavirus-induced BA mice, the expression of JAG1 and Notch2
      was significantly increased. Inhibition of the Notch pathway by DAPT in vivo
      ameliorated bile duct obstruction and delayed BA-induced mortality. The serum
      levels of inflammation cytokines (TNF-alpha, IL-2, IL-8, and IL-18) were reduced
      by inhibiting the Notch pathway. The expression of CK19, Sox9, and EpCAM was
      significantly increased in BA liver, while DAPT treatment decreased the
      expression of CK19, Sox9, and EpCAM. CONCLUSION: Notch activation is involved in
      the pathogenesis of BA by promoting the differentiation of hepatic progenitor
      cells into cholangiocytes.

PMID- 30196282
TI  - Ganoderma Lucidum Polysaccharide Peptide Alleviates Hepatoteatosis via Modulating
      Bile Acid Metabolism Dependent on FXR-SHP/FGF.
AB  - BACKGROUND/AIMS: Non-alcoholic fatty liver disease (NAFLD) encompasses a series
      of pathologic changes ranging from steatosis to steatohepatitis, which may
      progress to cirrhosis and hepatocellular carcinoma. The purpose of this study was
      to determine whether ganoderma lucidum polysaccharide peptide (GLPP) has
      therapeutic effect on NAFLD. METHODS: Ob/ ob mouse model and ApoC3 transgenic
      mouse model were used for exploring the effect of GLPP on NAFLD. Key metabolic
      pathways and enzymes were identified by metabolomics combining with KEGG and
      PIUmet analyses and key enzymes were detected by Western blot. Hepatosteatosis
      models of HepG2 cells and primary hepatocytes were used to further confirm the
      therapeutic effect of GLPP on NAFLD. RESULTS: GLPP administrated for a month
      alleviated hepatosteatosis, dyslipidemia, liver dysfunction and liver insulin
      resistance. Pathways of glycerophospholipid metabolism, fatty acid metabolism and
      primary bile acid biosynthesis were involved in the therapeutic effect of GLPP on
      NAFLD. Detection of key enzymes revealed that GLPP reversed low expression of
      CYP7A1, CYP8B1, FXR, SHP and high expression of FGFR4 in ob/ob mice and ApoC3
      mice. Besides, GLPP inhibited fatty acid synthesis by reducing the expression of
      SREBP1c, FAS and ACC via a FXR-SHP dependent mechanism. Additionally, GLPP
      reduced the accumulation of lipid droplets and the content of TG in HepG2 cells
      and primary hepatocytes induced by oleic acid and palmitic acid. CONCLUSION: GLPP
      significantly improves NAFLD via regulating bile acid synthesis dependent on FXR
      SHP/FGF pathway, which finally inhibits fatty acid synthesis, indicating that
      GLPP might be developed as a therapeutic drug for NAFLD.

PMID- 30196283
TI  - Integrin beta3 Mediates the Endothelial-to-Mesenchymal Transition via the Notch
      Pathway.
AB  - BACKGROUND/AIMS: Neointimal hyperplasia is responsible for stenosis, which
      requires corrective vascular surgery, and is also a major morphological feature
      of many cardiovascular diseases. This hyperplasia involves the endothelial-to
      mesenchymal transition (EndMT). We investigated whether integrin beta3 can
      modulate the EndMT, as well as its underlying mechanism. METHODS: Integrin beta3
      was overexpressed or knocked down in human umbilical vein endothelial cells
      (HUVECs). The expression of endothelial markers and mesenchymal markers was
      determined by real-time reverse transcription PCR (RT-PCR), immunofluorescence
      staining, and western blot analysis. Notch signaling pathway components were
      detected by real-time RT-PCR and western blot analysis. Cell mobility was
      evaluated by wound-healing, Transwell, and spreading assays. Fibroblast-specific
      protein 1 (FSP-1) promoter activity was determined by luciferase assay. RESULTS:
      Transforming growth factor (TGF)-beta1 treatment or integrin beta3 overexpression
      significantly promoted the EndMT by downregulating VE-cadherin and CD31 and
      upregulating smooth muscle actin alpha and FSP-1 in HUVECs, and by enhancing cell
      migration. Knockdown of integrin beta3 reversed these effects. Notch signaling
      was activated after TGF-beta1 treatment of HUVECs. Knockdown of integrin beta3
      suppressed TGF-beta1-induced Notch activation and expression of the Notch
      downstream target FSP-1. CONCLUSION: Integrin beta3 may promote the EndMT in
      HUVECs through activation of the Notch signaling pathway.

PMID- 30196284
TI  - Enhanced Expression of TGFBI Promotes the Proliferation and Migration of Glioma
      Cells.
AB  - BACKGROUND/AIMS: Transforming growth factor beta-induced protein (TGFBI) is an
      extracellular matrix protein induced by TGF-beta. Previous studies have reported
      that the abnormal expression of TGFBI is related to the occurrence and
      development of some types of cancers, while the role of TGFBI in glioma is
      uncertain. METHODS: The association between TGFBI expression and the prognosis of
      patients with glioma was analyzed based on data obtained from The Cancer Genome
      Atlas database. TGFBI expression was analyzed in 3 normal human brains and 57
      cases of human gliomas by immunohistochemistry followed by an evaluation of the
      relationships between TGFBI expression and clinic-pathological features.
      Furthermore, the RNA interference plasmid pSUPER-shTGFBI was constructed and
      transfected into U87 and U251 cells to explore the effect of short hairpin RNA
      against TGFBI (shTGFBI) on cell proliferation, migration, invasion and apoptosis.
      Western blot analysis was performed to examine the expression of proteins related
      to apoptosis and proteins in the PI3K/Akt signaling pathway. RESULTS: High TGFBI
      expression was found to be associated with poor prognosis in patients with
      glioblastoma multiforme. Immunohistochemistry showed that TGFBI expression was
      significantly higher in glioma tissue than in normal human brain tissues. The
      expression level of TGFBI showed no significant correlation with age, sex, lymph
      node metastasis, or pathological grade. sh-TGFBI could inhibit proliferation,
      invasion and migration and induce apoptosis in U87 and U251 cells in vitro.
      Furthermore, the phosphorylation levels of AKT and mTOR declined significantly in
      sh-TGFBI transfected U81 and U251 cells when compared with control. CONCLUSION:
      TGFBI was up-regulated in glioma cells and played a promoting role in the growth
      and motility of U87 and U251 cells. These results suggested that TGFBI has the
      potential to be a diagnostic marker and to serve as a target for the treatment of
      gliomas.

PMID- 30196285
TI  - Anti-Inflammatory Activity of Dehydroandrographolide by TLR4/NF-kappaB Signaling
      Pathway Inhibition in Bile Duct-Ligated Mice.
AB  - BACKGROUND/AIMS: Clinically, biliary obstruction is often accompanied by
      progressive inflammation. Dehydroandrographolide (DA) possesses anti-inflammatory
      properties. However, the anti-inflammatory activities of DA in cholestatic liver
      injury remain unclear. METHODS: Mice were administered with DA by intraperitoneal
      injection after bile duct ligation (BDL) on day 1. Then mice were subjected to an
      ileocecal vein injection of lipopolysaccharide (LPS). Liver function markers,
      histology, pro-inflammatory cytokine levels, NF-kappaB activation and fibrosis
      formation were evaluated in BDL mice with LPS. LPS binding to primary Kupffer
      cells was examined by high-content cytometers. RESULTS: DA was shown to greatly
      lower initially higher than normal levels of alanine aminotransferase (ALT) and
      total bilirubin (TBIL) in the serum and liver of BDL mice with LPS. DA exerted
      hepatic protective effects that were also confirmed by prolonged survival of BDL
      mice with LPS. Liver histopathology showed reduced inflammatory cellular
      infiltration, bile duct proliferation, and biliary necrosis with DA treatment.
      Furthermore, DA reduced the expression levels of tumor necrosis factor (TNF)
      alpha and interleukin (IL)-6 in liver tissue and plasma and showed decreased NF
      kappaB activation in BDL mice with LPS. DA could prevent LPS binding to primary
      Kupffer cells in the normal liver and BDL mice liver. DA also suppressed LPS
      stimulated inflammatory responses by blocking the interaction between LPS and
      TLR4 in primary Kupffer cells and human LX-2 cells, thereby inhibiting NF-kappaB
      activation. CONCLUSION: DA inhibition of inflammation against liver damage
      following BDL with LPS may be a promising agent for the treatment of cholestatic
      liver injury.

PMID- 30196286
TI  - Stereoscopic Vision in Macular Telangiectasia Type 2.
AB  - PURPOSE: To investigate stereoscopic vision in patients with macular
      telangiectasia (MacTel) type 2 and correlate paracentral sensitivity loss to
      reduced stereoscopic function. METHODS: In a prospective single-center study, 50
      patients with MacTel type 2 and 25 age-matched controls were investigated.
      Stereoscopic function was evaluated with Lang I, Titmus, and TNO tests.
      Sensitivity of the central 16 degrees  was tested using fundus-controlled
      perimetry (microperimetry). Functional loss was quantified as depth, size, and
      localization of scotomata. RESULTS: Both the Titmus and the TNO test revealed
      significantly reduced stereoscopic vision in patients compared to controls (p <
      0.0001 for both). This applied even to patients with only relative or monocular
      paracentral scotoma. A strong correlation was observed for reduced stereoscopic
      vision with horizontal scotoma size and with the distance of scotomata from the
      foveal center. CONCLUSIONS: The results indicate that stereoscopic vision is
      impaired early in patients with MacTel type 2. A paracentral sensitivity loss,
      even if mild and limited to one eye, may considerably interfere with stereoscopic
      function despite normal visual acuity. Projection of paracentral scotomata within
      the patient's central visual field plays an important role in stereoscopic vision
      and should be considered when interpreting stereoscopic test results.

PMID- 30196287
TI  - Down-Regulation of miR-327 Alleviates Ischemia/Reperfusion-Induced Myocardial
      Damage by Targeting RP105.
AB  - BACKGROUND/AIMS: Micro RNAs (miRNAs) play a very important role in myocardial
      ischemia/ reperfusion injury (MIRI), including in inflammation, apoptosis, and
      angiogenesis. Previous studies have demonstrated up-regulation of miR-327 in
      renal ischemia/reperfusion injury and MIRI. Via TargetScan, we found RP105 is a
      possible target gene of miR-327; our previous studies have also confirmed that
      RP105 acted as a cardioprotective protein in MIRI by reducing inflammation.
      However, the regulatory effect of miR-327 on RP105 has not previously been
      proposed. In our study, we aimed to identify the regulatory effect of miR-327 on
      RP105 protein in MIRI rats. METHODS: Sixty male Sprague-Dawley rats were randomly
      divided into five groups, which were pre-treated with saline (sham and
      ischemia/reperfusion group), adenovirus-expressing miR-327-RNAi (Ad-miR-327-i
      group), control (Ad-NC group), or pri-miR-327 (Ad-miR-327 group) treatments.
      Three days later, the rat MIRI model was established by ischemia for 30 min,
      followed by reperfusion for 3 h. Myocardium and plasma were harvested and
      assessed. RESULTS: miR-327 was increased by nearly 3-fold both in myocardium and
      plasma, which down-regulated RP105 in a 3'-untranslated region-dependent manner,
      and down-regulation of miR-327 via adenovirus transfection indirectly suppressed
      the TLR4/ TLR2-MyD88-NF-kappaB signaling axis activation via up-regulation of
      RP105, which subsequently resulted in reduced myocardial infarct size, attenuated
      cardiomyocyte destruction, and alleviated inflammation. In contrast, up
      regulation of miR-327 induced the opposite effect. CONCLUSION: Down-regulation of
      miR-327 exerts a cardioprotective effect against MIRI by reducing inflammation,
      which may constitute a promising molecular therapeutic target for treating MIRI.

PMID- 30196288
TI  - Discovery and Characterization of a High-Affinity Small Peptide Ligand, H1,
      Targeting FGFR2IIIc for Skin Wound Healing.
AB  - BACKGROUND/AIMS: How to aid recovery from severe skin injuries, such as burns,
      chronic or radiation ulcers, and trauma, is a critical clinical problem. Current
      treatment methods remain limited, and the discovery of ideal wound-healing
      therapeutics has been a focus of research. Functional recombinant proteins such
      as basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) have
      been developed for skin repair, however, some disadvantages in their use remain.
      This study reports the discovery of a novel small peptide targeting fibroblast
      growth factor receptor 2 IIIc (FGFR2IIIc) as a potential candidate for skin wound
      healing. METHODS: A phage-displayed peptide library was used for biopanning
      FGFR2IIIc-targeting small peptides. The selected small peptides binding to
      FGFR2IIIc were qualitatively evaluated by an enzyme-linked immunosorbent assay.
      Their biological function was detected by a cell proliferation assay. Among them,
      an optimized small peptide named H1 was selected for further study. The affinity
      of the H1 peptide and FGFR2IIIc was determined by an isothermal titration
      calorimetry device. The ability of theH1 peptide to promote skin wound repair was
      investigated using an endothelial cell tube formation assay and wound healing
      scratch assay in vitro. Subsequently, the H1 peptide was assessed using a rat
      skin full-thickness wound model and chorioallantoic membrane (CAM) assays in
      vivo. To explore its molecular mechanisms, RNA-Seq, quantitative real-time PCR,
      and western blot assays were performed. Computer molecular simulations were also
      conducted to analyze the binding model. RESULTS: We identified a novel FGFR2IIIc
      targeting small peptide, called H1, with 7 amino acid residues using phage
      display. H1 had high binding affinity with FGFR2IIIc. The H1 peptide promoted the
      proliferation and motility of fibroblasts and vascular endothelial cells in
      vitro. In addition, the H1 peptide enhanced angiogenesis in the chick
      chorioallantoic membrane and accelerated wound healing in a rat full-thickness
      wound model in vivo. The H1 peptide activated both the PI3K-AKT and MAPK-ERK1/2
      pathways and simultaneously increased the secretion of vascular endothelial
      growth factor. Computer analysis demonstrated that the model of H1 peptide
      binding to FGFR2IIIc was similar to that of FGF2 and FGFR2IIIc. CONCLUSION: The
      H1 peptide has a high affinity for FGFR2IIIc and shows potential as a wound
      healing agent. As a substitute for bFGF, it could be developed into a novel
      therapeutic candidate for skin wound repair in the future.

PMID- 30196289
TI  - Icariside II, a Phosphodiesterase-5 Inhibitor, Attenuates Beta-Amyloid-Induced
      Cognitive Deficits via BDNF/TrkB/CREB Signaling.
AB  - BACKGROUND/AIMS: Icariside II (ICS II) is an active component from Epimedium
      brevicornum, a Chinese medicine extensively used in China. Our previous study has
      proved that ICS II protects against learning and memory impairments and neuronal
      apoptosis in the hippocampus induced by beta-amyloid25-35 (Abeta25-35) in rats.
      However, its in-depth underlying mechanisms remain still unclear. Hence this
      study was designed to explore the potential underlying mechanisms of ICS II by
      experiments with an in vivo model of Abeta25-35-induced cognitive deficits in
      rats combined with a neuronal-like PC12 cells injury in vitro model. METHODS: The
      cognitive deficits was measured using Morris water maze test, and apoptosis,
      intracellular reactive oxygen species (ROS) and mitochondrial ROS levels were
      detected by TUNEL, DCFH-DA and Mito-SOX staining, respectively. Expression of Bcl
      2, Bax, brain derived neurotrophic factor (BDNF), tyrosine receptor kinase B
      (TrkB), and cAMP response element binding (p-CREB) and active-Caspase 3 levels
      were evaluated by Western blot. RESULTS: It was found that ICS II, a
      phosphodiesterase-5 inhibitor, significantly attenuated cognitive deficits caused
      by Abeta25-35 injection in rats, and ICS II not only significantly enhanced the
      expression of BDNF and TrkB, but also activated CREB. Furthermore, ICS II also
      significantly abrogated Abeta25-35-induced PC12 cell injury, and inhibited
      Abeta25-35-induced intracellular reactive oxygen species (ROS) overproduction, as
      well as mitochondrial ROS levels. In addition, ICS II up-regulated the
      expressions of BDNF and TrkB consistent with the findings in vivo. ANA-12, a TrkB
      inhibitor, blocked the neuroprotective effect of ICS II on Abeta25-35-induced
      neuronal injury. CONCLUSION: ICS II mitigates Abeta25-35-induced cognitive
      deficits and neuronal cell injury by upregulating the BDNF/TrkB/CREB signaling,
      suggesting that ICS II can be used as a potential therapeutic agent for dementia,
      such as Alzheimer's disease.

PMID- 30196290
TI  - Activation of M3 Muscarinic Acetylcholine Receptors Delayed Cardiac Aging by
      Inhibiting the Caspase-1/IL-1beta Signaling Pathway.
AB  - BACKGROUND/AIMS: Because the prevalence of age-related cardiac impairment
      increases as the human lifespan increases, it is important to combat the effects
      of aging. Recently, the cardiac M3 muscarinic acetylcholine receptor (M3-mAChR)
      has been demonstrated to play important roles in cardiac development and in the
      pathogenesis of cardiac diseases. However, the role of M3-mAChR in aging remains
      largely unknown. Therefore, the aim of this study was to investigate the
      involvement of M3-mAChR in the progression of cardiac aging. METHODS: We
      established a cardiac aging model in mice through subcutaneous injection with D
      galactose at a dose of 100 mg/kg/day for 6 weeks. D-galactose was also used to
      induce aging in primary cultured neonatal mouse cardiomyocytes. The myocardium
      from mice was stained with hematoxylin and eosin for histological analysis. The
      protein expression levels of p53 and p21 were determined using western blotting.
      The mRNA and protein expression levels of M3-mAChR, caspase-1, and interleukin
      (IL)-1beta were determined using real-time PCR, immunohistochemical staining, and
      western blotting. RESULTS: The expression of M3-mAChR was down-regulated in the
      myocardium from aged mice and D-galactose-treated mice, while the expression
      levels of caspase-1 and its downstream molecule IL-1beta were significantly
      increased. The M3-mAChR agonist choline reduced the increase in caspase-1 in
      cardiomyocytes induced by D-galactose, which was reversed by the M3-mAChR
      antagonist 4-DAMP. Moreover, 4-DAMP promoted D-galactose-induced cardiomyocyte
      aging, which was attenuated by a caspase-1 inhibitor. CONCLUSION: Activation of
      M3-mAChR delayed cardiac aging by inhibiting the caspase-1/IL-1beta signaling
      pathway.

PMID- 30196291
TI  - Novel Polysaccharide H-1-2 from Pseudostellaria Heterophylla Alleviates Type 2
      Diabetes Mellitus.
AB  - BACKGROUND/AIMS: To investigate the potential therapeutic effect of novel
      polysaccharide H-1-2 from pseudostellaria heterophylla against type 2 Diabetes
      Mellitus (T2DM) and elucidate the underling molecular mechanisms. METHODS:
      Relative expression of HIF1alpha and Sirt1 in T2DM patients was determined via
      real-time PCR. The direct binding of HIF1alpha on Sirt1 promoter was validated by
      ChIP assay. The inhibitory regulation of Sirt1 by HIF1alpha was analyzed using
      luciferase reporter assay. The endogenous protein of HIF1alpha and Sirt1 in
      response to H-1-2 treatment was quantified by western blotting. The blood
      glucose, secreted insulin and serous lipid profiles were measured with ELISA
      kits. RESULTS: We consolidated that HIF1alpha and Sirt1 was dysregulated in T2DM
      patients and subjected to H-1-2 modulation. H-1-2 significantly inhibited hypoxia
      and up-regulated Sirt1 expression in EndoC-betaH1 cells. Accordingly, H-1-2
      enhanced glucose-stimulation insulin secretion and improved blood glucose and
      lipid profiles in T2DM cells, and elevated the glucose and insulin tolerance
      simultaneously. Furthermore, we demonstrated that H-1-2 alleviated T2DM via
      inhibition of hypoxia and up-regulation of Sirt1 in isolated pancreatic beta
      cells from T2DM rats. CONCLUSION: Our data unambiguously demonstrated H-1-2
      administration alleviated T2DM by enhancing Sirt1 expression through inhibition
      of hypoxia.

PMID- 30196292
TI  - Association of Low Zinc Finger Antiviral Protein Expression with Progression and
      Poor Survival of Patients with Hepatocellular Carcinoma.
AB  - BACKGROUND/AIMS: Zinc finger antiviral protein (ZAP) has been reported to be
      expressed in hepatocellular carcinoma (HCC), and ZAP expression is associated
      with apoptotic signaling in cancer cells. This study aimed at investigating the
      expression of ZAP in HCC cells and its significance in clinical pathology.
      METHODS: Real-time quantitative PCR and western blot assays were employed to
      detect ZAP RNA and protein expression in normal human hepatocytes, HCC cells, and
      five primary HCC cell lines. Immunohistochemistry was performed to detect ZAP
      expression in 147 paraffin-embedded HCC tissues and adjacent normal tissues. The
      clinical significance of ZAP expression was analyzed in tissue samples from
      patients with or without infection by hepatitis B virus (HBV). RESULTS: ZAP
      expression in HCC cells and human primary HCC cell lines was significantly lower
      than that of normal human hepatocytes. Among 147 HCC samples, ZAP expression was
      lower in HCC tissues than in adjacent normal tissues for 107 (77.0%) samples. In
      patients with HCC and HBV infection, ZAP expression was related to pathological
      grade (P < 0.05); in HBV-negative patients with HCC, ZAP expression was
      associated with tumor size (P < 0.05) and clinical stage (P < 0.05). The overall
      survival time in patients with low ZAP expression was significantly shorter than
      survival times of those with high ZAP expression (P < 0.05), especially for
      patients with moderately to well-differentiated HCC (Grade 1-2) and HCC at stage
      T1 and T2 (P < 0.05). Cox multivariate analysis showed that ZAP expression was an
      independent predictor of survival of patients with HCC (P < 0.01). CONCLUSION:
      Low ZAP expression is closely associated with disease progression and poor
      prognosis for patients with HCC.

PMID- 30196293
TI  - Complementary Feeding: Beyond Nutrition.
AB  - In this article, we will summarize the key non-nutritional aspects of the
      introduction of complementary feeding. Intestinal maturation related to starch
      digestion is relatively complete by the time complementary feeding is recommended
      to be initiated. A much more complex maturation is needed, however, from the
      neurodevelopmental standpoint as the infants need to be able to hold their head
      and trunk and be able to coordinate tongue movement followed by swallowing.
      Issues can arise in infants with a history of medical problems as well as when
      caretakers cannot handle the initial difficulties or want to impose certain
      rigidity to the learning process. The introduction of complementary feedings is
      also part of the early steps in introduction to human socialization. In that
      regard, it sets up the infant to internalize and accept the diversity of food
      textures and food choices. Early refusal of some food items is common and should
      not be interpreted as being disliked. Multiple attempts should be made to
      incorporate new food items. To accomplish these dynamics, caregivers need
      comprehensive education and relevant information.

PMID- 30196294
TI  - Complementary Feeding in Developed Countries: The 3 Ws (When, What, and Why?).
AB  - While a wide knowledge exists on the effects of breast milk or infant formula on
      growth and infant development, less attention has been paid to the importance of
      complementary feeding (CF). This review focuses on current recommendations for
      optimal introduction of CF in healthy full-term European infants and discusses
      the potential impact of this type of feeding on health outcomes. Overall,
      exclusive breastfeeding is recommended at least for 4 months and preferable for 6
      months, followed by the introduction of CF alongside breast milk; infants'
      nutrient requirements must meet the differences between nutrients provided by
      breast milk and the estimated total needs. There is growing evidence that healthy
      feeding practices during the CF period have positive short- and long-term effects
      on optimal growth, body composition, neurodevelopment, healthy food preferences,
      and gut microbiota composition and function; adequate and healthy CF may also
      diminish the risk of infections, allergies, type 1 diabetes mellitus, as well as
      celiac and non-communicable diseases. Following the expert recommendations, the
      design of nutritional strategies must encourage parents to provide a healthy
      lifestyle for their offspring. Future research should aim to optimize timing,
      content, and methods of CF; furthermore, it is necessary to explore future CF
      targeted health-promoting strategies in early life (appetite regulation, eating
      patterns, eating behavior, gut dysbiosis, etc.) to prevent growth/obesity
      outcomes, immune system related-diseases or non-communicable diseases in later
      life.

PMID- 30196295
TI  - Impact of Food Fortification on Child Growth and Development during Complementary
      Feeding.
AB  - There appears to be increasing evidence of the relationship between infant
      feeding practices and growth during infancy. Effective complementary feeding has
      demonstrated an observable positive effect on the linear growth of a child within
      the first 24 months of life. It appears that improved complementary feeding is
      directly proportional to the linear growth of a child. Fortification of commonly
      used food vehicles provides an opportunity for increasing nutrient intake during
      infancy and has the potential to improve growth and development dimensions. This
      review scanned through 186 articles from common search engines, mainly PubMed,
      BioMed Central, and Google Scholar. The result based on a systematic review of
      articles which met the minimum selection criteria identified milk, iodine, maize
      meal porridge, and vegetable oils as recurring fortification vehicles in the
      context of complementary feeding. A significant impact of fortification on linear
      and cognitive growth was demonstrated recurrently across the included empirical
      studies. However, the review reflects outcomes that still do not demonstrate
      direct cause and effect relationships but rather implied meaning in the
      relationship matrix.

PMID- 30196296
TI  - Overnutrition: Does Complementary Feeding Play a Role?
AB  - Globally, obesity is considered an epidemic due to an increase in its prevalence
      and severity especially among young children and adolescents. This nutritional
      disorder is not limited to affluent countries as it is becoming increasingly
      prevalent in developing countries. Obesity is associated not only with
      cardiovascular, endocrine, gastrointestinal, orthopedic, and respiratory
      diseases, but also with psychological complications, implying a problem of far
      reaching consequences for health and health services. Recently, evidence-based
      studies have shown that the duration of exclusive breastfeeding and the type of
      complementary feeds during the weaning period of an infant may have an effect on
      overnutrition later on in life. Thus, stemming the tide of obesity early on in
      life would potentially decrease the prevalence and complications of adult
      obesity, which could have significant implications for health care and the
      economy at large. This review explores the role of complementary feeding in
      obesity and approaches to prevention and treatment of childhood obesity by
      summarizing key systematic reviews. In conclusion, we found that although the
      relationship between complementary feeding and childhood obesity has been
      suspected for a long time, specific risk parameters are not as firmly
      established. Early introduction of complementary feeds (before the 4th month of
      life), high protein and energy content of feeds, and nonadherence to feeding
      guidelines may be associated with overweight and obesity later in life.

PMID- 30196297
TI  - Editorial.

PMID- 30196298
TI  - Connexin 43: a New Therapeutic Target Against Chronic Kidney Disease.
AB  - Chronic kidney disease is an incurable to date pathology with a continuously
      growing incidence that contributes to the increase of the number of deaths
      worldwide. With currently no efficient prognostic or therapeutic options being
      available, the only possibility for treatment of end-stage renal disease is renal
      replacement therapy through dialysis or transplantation. Understanding the
      molecular mechanisms participating in the progression of renal diseases and
      uncovering the pathways implicated will permit the identification of novel and
      more efficient targets of therapy. Connexin43 was recently identified as a novel
      player in the development of chronic kidney disease. It was found de novo
      expressed and/or differentially localized in various renal cell populations
      during progression of renal disease, indicating an abnormal connexin signaling,
      both in patients and animal models. Subsequent in vivo studies demonstrated that
      connexin43 is involved in mediating inflammatory and fibrotic processes
      contributing to renal damage. Genetic, pharmaco-genetic or peptide-based
      inhibition of connexin43 in animal models and cell culture systems was successful
      in preventing the progression of the pathology and preserving the cell
      phenotypes. This review will summarize the recent advances on connexin43 in the
      field of kidney diseases and discuss the potential of future connexin43-based
      therapies against chronic kidney disease.

PMID- 30196299
TI  - S100A4 Knockout Sensitizes Anaplastic Thyroid Carcinoma Cells Harboring
      BRAFV600E/Mt to Vemurafenib.
AB  - BACKGROUND/AIMS: Anaplastic thyroid cancer (ATC), with 25% BRAFV600E mutation, is
      one of the most lethal human malignancies that currently has no effective
      therapy. Vemurafenib, a BRAFV600E inhibitor, has shown promise in clinical
      trials, including ATC patients, but is being hampered by the acquisition of drug
      resistance. Therefore, combination therapy that includes BRAFV600E inhibition and
      avoids resistance is a clinical need. METHODS: ATC cell lines 8505C
      (BRAFV600E/mt), SW1736 (BRAFV600E/mt), KAT18 (BRAFV600E/wt) and Cal
      62(BRAFV600E/wt) cells were used in the study. The ability of S100A knockout or
      /and in combination with the BRAF inhibitor vemurafenib on growth, apoptosis,
      invasion and apoptosis in ATC cells in vitro was demonstrated by MTT and BrdUrd
      incorporation assay, Annexin-V-FITC staining analyzed by flow cytometry,
      Transwell migration and Matrigel invasion assay. S100A4,pERK1/2, pAKT and
      pROCK1/2 protein was detected by western blot assay; Small molecule inhibitors of
      Y27632, U0126, MK-2206 and constitutively active forms of pCDNA-Myc-pERK, pCMV6
      HA-Akt, pCMV-RhoA were employed, and the mechanistic studies were performed. We
      assessed the efficiency of in vivo combination treatment with S100A4 knockout and
      Vemurafenib on tumors. RESULTS: S100A4 knockout induced apoptosis and reduced
      proliferation by inactivation of pAKT and pERK signals, and inhibited invasion
      and migration by inactivation of pAKT and RhoA/ROCK1/2 signals in 8505C or Cal-62
      cells in vitro, and vice versa in SW1736 and KAT18 cells. Vemurafenib did not
      affect apoptosis of both 8505C and SW1736 cells, but reduced proliferation via
      arresting cell cycle, and promoted cell migration and invasion in vitro.
      Combination treatment with S100A4 knockdown and vemurafenib reduced cell
      proliferation, migration and invasion in vitro compared to the S100A4 knockdown
      or Vemurafenib alone. Vemurafenib treatment resulted in a transient inhibition of
      pERK expression and gradually activation of pAKT expression, but quickly recovery
      from ERK1/2 activation inhibition by vemurafenib treatment in 4 h for SW1736 and
      8505C cells. Combined treatment completely inhibited ERK1/2 and AKT activation
      during 48 h. In an in vivo mouse model of SW1736 and 8505C, vemurafenib treatment
      alone did not significantly inhibit tumor growth in both of the tumors, but
      inhibited tumor growth in combined groups. CONCLUSION: Our results show S100A4
      knockout alone inhibits ATC cells (rich endogenous S100A4) survival and invasion,
      regardless of the BRAFV600E status, and potentiates the effect of vemurafenib on
      tumor regression in vitro and in vivo. In addition, S100A4 knockout potently
      inhibits the recovery from ERK1/2 activation inhibition and the AKT activation
      following vemurafenib treatment and reversed the vemurafenib resistance. This
      therapeutic combination may be of benefit in patients with ATC.

PMID- 30196300
TI  - Blood-Based Therapies to Combat Aging.
AB  - Dysfunction associated with the aging process positions aging as a leading
      culprit for development of devastating diseases and mounting health-care costs.
      Many age-associated conditions for which aging increases risk are neurological
      disorders with no effective treatments, including Alzhei-mer's disease. As the
      proportion of aged individuals continues to rise in the coming decades, aging
      related costs are expected to increase dramatically. Diverse approaches have
      emerged to meet the clinical need to treat aging and its associated conditions,
      including those aimed at increasing longevity, slowing the aging process itself,
      and improving healthspan. An emerging approach takes advantage of molecules
      circulating in the blood to limit or reverse aspects of aging in various organs
      throughout the body. Efforts are underway to translate these findings into novel
      therapeutics that harness the activity of youth-associated molecules present
      within blood. Here, we discuss the current state of blood-based approaches in
      this arena. Despite the apparent ease with which blood products might conceivably
      be applied as treatment paradigms, we propose that challenges nonetheless exist,
      which may be overcome with mechanistic studies that identify common pathways for
      targeted therapeutics.

PMID- 30196301
TI  - Switching from Epoetin Alfa (Epogen(r)) to Epoetin Alfa-Epbx (RetacritTM) Using a
      Specified Dosing Algorithm: A Randomized, Non-Inferiority Study in Adults on
      Hemodialysis.
AB  - BACKGROUND: For patients with anemia undergoing hemodialysis, erythropoiesis
      stimulating agents (ESAs) are typically dosed via precise algorithms. Using one
      such algorithm, we assessed the maintenance of hemoglobin levels in patients
      switched from epoetin alfa reference product (Epogen(r)) to epoetin alfa-epbx
      (RetacritTM; a biosimilar to US-licensed Epogen(r)/Procrit(r)). METHODS: This
      randomized, open-label, non-inferiority study was conducted at Fresenius Medical
      Care North America (FMCNA) hemodialysis centers. Patients with anemia and chronic
      kidney disease undergoing maintenance hemodialysis and receiving routine
      intravenous (IV) Epogen(r) were randomized 1: 1 to switch to IV RetacritTM or
      continue standard-of-care (Epogen(r)) for 24 weeks, using analogous versions of
      the FMCNA ESA-dosing algorithm. The primary endpoint was the proportion of time
      patients' hemoglobin was 9-11 g/dL during weeks 17-24. RESULTS: Of 432 randomized
      patients, 418 received treatment (RetacritTM, n = 212; standard-of-care, n = 206)
      and comprised the full analysis set. A similar proportion of patients
      discontinued from each arm. The proportion of time patients' hemoglobin was
      within the target range was 61.9% (95% CI 57.5-66.2) in the RetacritTM arm and
      63.3% (95% CI 58.7-67.7) in the standard-of-care arm. The difference in
      proportions between treatment arms was -1.4% (95% CI -7.6 to 4.9), and the lower
      bound of the confidence interval was within the pre-specified non-inferiority
      margin of -12.5%. There was no statistically significant difference between arms
      in the mean change from baseline in the weekly mean ESA dose during weeks 17-24,
      and no clinically relevant differences in safety outcomes. CONCLUSIONS: Switching
      to RetacritTM was non-inferior to continuing -Epogen(r) in maintaining hemoglobin
      levels in patients receiving hemodialysis, when both ESAs were dosed using a
      specified algorithm (ClinicalTrials.gov, NCT02504294).

PMID- 30196302
TI  - Low-Level Aflatoxin B1 Promotes Influenza Infection and Modulates a Switch in
      Macrophage Polarization from M1 to M2.
AB  - BACKGROUND/AIMS: Swine influenza virus (SIV) is a major pathogen of both animals
      and humans. Afatoxin B1 (AFB1) is one of the most common mycotoxins in feed and
      food. However, the central contribution of AFB1 to SIV infection remains unclear.
      METHODS: Here, TCID50 assays, fluorescence-based quantitative real-time PCR,
      western blotting, immunofluorescence staining, histopathological examination,
      flow cytometry and scanning electron microscopy were performed to investigate the
      involvement and underlying mechanism of AFB1 in SIV infection in vivo and in
      vitro using mouse models and porcine alveolar macrophage (PAM) models,
      respectively. RESULTS: The in vivo study showed that low levels of AFB1 promoted
      SIV infection and increased its severity, as demonstrated by the increased mRNA
      expression of viral matrix protein (M); by the increased protein expression of
      nucleoprotein (NP), matrix protein 1 and ion channel protein; and by animal
      weight loss, lung index and lung histologic damage. In addition, the increased
      occurrence of SIV infection accompanied by increases in the level of IL-10 in
      sera and lungs, in the spleen index and in the number of CD206-positive mouse
      alveolar macrophages but decreases in the level of TNF-alpha in sera and lungs,
      in the thymus index and in the number of CD80-positive mouse alveolar macrophages
      was observed in SIV-infected mice after low-level AFB1 exposure. The in vitro
      study showed that low concentrations of AFB1 promoted SIV infection, as
      demonstrated by the increases in viral titers and viral M mRNA and NP expression
      levels in SIV-infected PAMs as well as by the number of cells positive for NP
      protein expression. Furthermore, AFB1 promoted the polarization of SIV-infected
      PAMs to the M1 phenotype at 8 hpi and to the M2 phenotype at 24 hpi, as measured
      by the increases in IL-10 expression and in the number of CD206-positive PAMs as
      well as by the morphological changes observed by scanning electron microscopy.
      The administration of the immune stimulant lipopolysaccharide (LPS) reversed the
      switch in PAM polarization from M2 to M1 and thereby counteracted the promotion
      of influenza virus infection induced by AFB1. CONCLUSION: Our results are the
      first to confirm that low-level exposure to AFB1 promotes SIV infection and
      modulates a switch in macrophage polarization from M1 to M2. The work reported
      here provides important data that point to a role for AFB1 in SIV infection, and
      it opens a new field of study.

PMID- 30196303
TI  - FGF18 Enhances Migration and the Epithelial-Mesenchymal Transition in Breast
      Cancer by Regulating Akt/GSK3beta/Beta-Catenin Signaling.
AB  - BACKGROUND/AIMS: Fibroblast growth factors (FGFs) and their high-affinity
      receptors contribute to autocrine and paracrine growth stimulation in several
      human malignant tumors, including breast cancer. However, the mechanisms
      underlying the carcinogenic actions of FGF18 remain unclear. METHODS: The
      transcription level of FGF18 under the hypoxic condition was detected with
      quantitative PCR (qPCR). A wound-healing assay was performed to assess the role
      of FGF18 in cell migration. A clonogenicity assay was used to determine whether
      FGF18 silencing affected cell clonogenicity. Western blotting was performed to
      investigate Akt/GSK3beta/beta-catenin pathway protein expression. Binding of beta
      catenin to the target gene promoter was determined by chromatin
      immunoprecipitation (ChIP) assays. RESULTS: FGF18 promoted the epithelial
      mesenchymal transition (EMT) and migration in breast cancer cells through
      activation of the Akt/GSK3beta/beta-catenin pathway. FGF18 increased Akt-Ser473
      and -Thr308 phosphorylation, as well as that of GSK3beta-Ser9. FGF18 also
      enhanced the transcription of proliferation-related genes (CDK2, CCND2, Ki67),
      metastasis-related genes (TGF-beta, MMP-2, MMP-9), and EMT markers (Snail-1,
      Snail-2, N-cadherin, vimentin, TIMP1). beta-catenin bound to the target gene
      promoter on the ChIP assay. CONCLUSION: FGF18 contributes to the migration and
      EMT of breast cancer cells following activation of the Akt/GSK3beta/beta-catenin
      pathway. FGF18 expression may be a potential prognostic therapeutic marker for
      breast cancer.

PMID- 30196304
TI  - In Vitro Analyses of Novel HCN4 Gene Mutations.
AB  - BACKGROUND/AIMS: The hyperpolarization-activated cyclic nucleotide-gated cation
      channel HCN4 contributes significantly to the generation of basic cardiac
      electrical activity in the sinus node and is a mediator of modulation by beta
      adrenergic stimulation. Heterologous expression of sick sinus syndrome (SSS) and
      bradycardia associated mutations within the human HCN4 gene results in altered
      channel function. The main aim was to describe the functional characterization of
      three (two novel and one known) missense mutations of HCN4 identified in families
      with SSS. METHODS: Here, the two-electrode voltage clamp technique on Xenopus
      laevis oocytes and confocal imaging on transfected COS7 cells respectively, were
      used to analyze the functional effects of three HCN4 mutations; R378C, R550H, and
      E1193Q. Membrane surface expressions of wild type and the mutant channels were
      assessed by confocal microscopy, chemiluminescence assay, and Western blot in
      COS7 and HeLa cells. RESULTS: The homomeric mutant channels R550H and E1193Q
      showed loss of function through increased rates of deactivation and distinctly
      reduced surface expression in all three homomeric mutant channels. HCN4 channels
      containing R550H and E1193Q mutant subunits only showed minor effects on the
      voltage dependence and rates of activation/deactivation. In contrast, homomeric
      R378C exerted a left-shifted activation curve and slowed activation kinetics.
      These effects were reduced in heteromeric co-expression of R378C with wild-type
      (WT) channels. CONCLUSION: Dysfunction of homomeric/heteromeric mutant HCN4
      R378C, R550H, and E1193Q channels in the present study was primarily caused by
      loss of function due to decreased channel surface expression.

PMID- 30196305
TI  - Prognostic Significance of Asymptomatic Brain Natriuretic Peptide Elevation at
      Nephrology Referral in Patients with Chronic Kidney Disease.
AB  - BACKGROUND: It is unclear whether asymptomatic elevation of brain natriuretic
      peptide (BNP) is associated with cardiovascular events (CVEs) or heart failure
      (HF) in predialysis chronic kidney disease (CKD) patients. METHODS: We measured
      BNP in 482 asymptomatic predialysis patients with CKD stages 2-5 at nephrology
      referral between August 2004 and October 2010, and followed them prospectively to
      investigate the prognostic significance of BNP using Cox models and receiver
      operating characteristic (ROC) analyses. The primary composite end point was the
      time to death or the first nonfatal CVEs. Secondary end points included CVEs
      including sudden death, HF and all-cause death. RESULTS: The median age was 67
      years (male, 67.4%; diabetic nephropathy, 33.4%), and estimated glomerular
      filtration rate was 20.1 mL/min/1.73 m2. The primary end point occurred in 92
      patients. CVEs including sudden death, HF and all-cause death occurred in 66, 35,
      and 54 patients, respectively during a median follow-up period of 37.7 months.
      Multivariate analyses showed that BNP level was significantly associated with the
      primary end point (hazard ratio [HR] 1.241; 95% CI 1.020-1.511; p = 0.031), CVEs
      (HR 1.337; 95% CI 1.067-1.675; p = 0.012) and HF (HR 1.489; 95% CI 1.059-2.091; p
      = 0.022), but not associated with all-cause death (HR 1.081; 95% CI 0.829-1.410;
      p = 0.565). The ROC curves showed that the optimal predictive BNP levels for the
      primary end point, CVEs and HF were 92.5, 127.0, and 274.6 (pg/mL) respectively.
      CONCLUSION: Asymptomatic elevation of BNP is strongly predictive for CVEs and HF,
      which might help to integrate cardio-renal risk stratification in predialysis CKD
      patients.

PMID- 30196306
TI  - Impact of Thermo-Expandable Memokath Ureteral Stent on Renal Function in the
      Management of Ureteroileal Anastomotic Stricture.
AB  - PURPOSE: The study aimed to assess the impact of the Memokath 051 stent (MK) on
      glomerular filtration rate (GFR) and split renal function in the management of
      ureteroileal anastomotic strictures. MATERIALS AND METHODS: We treated 6 patients
      in the ages of 66-77 years, 2 of whom had bilateral strictures, with a total of 8
      ureteroileal strictures using the MK stent. Five patients had chronic kidney
      disease (CKD) prior to MK insertion. Mean time between conduit surgery and MK
      insertion was 28.4 months. Serum creatinine, GFR, and MAG-3 renography were
      determined before stent insertion and postoperatively at 3 months. RESULTS:
      Postoperative complications at 3-month follow-up included migration in 2
      patients, occlusion in 2 patients, and urinary tract infection in 4 patients. The
      mean stent indwelling time was 353.4 +/- 169.3 days. Mean preoperative
      creatinine, GFR, right, and left split renal function were 158.3 +/- 76.3
      MUmol/L, 43.6 +/- 32.9 mL/min/1.73 m2, 52.8 +/- 22.2%, and 47.1 +/- 22.2%,
      respectively. Mean postoperative values were 168.1 +/- 84 MUmol/L (p = 0.84),
      40.8 +/- 28.4 mL/min/1.73 m2 (p = 0.56), 51.1 +/- 18.3% (p = 1), and 48.8 +/-
      18.3% (p = 1), respectively. CONCLUSION: MK stent is a safe and efficient
      minimally invasive long-term treatment option to preserve GFR in patients who
      develop CKD through ureteroileal anastomotic stricture. In spite of MK stent
      insertion and alleviation of obstruction, it was presumably inserted too late to
      improve renal function.

PMID- 30196307
TI  - Label-Free Spectral Imaging Unveils Biochemical Mechanisms of Low-Level Laser
      Therapy on Spinal Cord Injury.
AB  - BACKGROUND/AIMS: Low-level laser therapy (LLLT) leads to complex photochemical
      responses during the healing process of spinal cord injury (SCI). Confocal Raman
      Microspectral Imaging (in combination with multivariate analysis) was adopted to
      illustrate the underlying biochemical mechanisms of LLLT treatment on a SCI rat
      model. METHODS: Using transversal tissue sections, the Raman spectra can identify
      areas neighboring the injury site, glial scar, cavity, and unharmed white matter,
      as well as their correlated cellular alterations, such as demyelination and up
      regulation of chondroitin sulfate proteoglycans (CSPGs). Multivariate data
      analysis methods are used to depict the underlying therapeutic effects by
      highlighting the detailed content and distribution variations of the biochemical
      constituents. RESULTS: It is confirmed that photon-tissue interactions might lead
      to a decay of the inhibitory response to remyelination by suppressing CSPG
      expression, as also morphologically demonstrated by reduced glial scar and cavity
      areas. An inter-group comparison semi-quantitatively confirms changes in lipids,
      phosphatidic acid, CSPGs, and cholesterol during SCI and its LLLT treatment,
      paving the way for in vitro and in vivo understanding of the biochemical changes
      accompanying pathobiological SCI events. CONCLUSION: The achieved results in this
      work not only have once again proved the well-known cellular mechanisms of SCI,
      but further illustrate the underlying biochemical variability during LLLT
      treatment, which provide a sound basis for developing real-time Raman
      methodologies to monitor the efficacy of the SCI LLLT treatment.

PMID- 30196309
TI  - Marsdenia Tenacissima Extract Inhibits Proliferation and Promotes Apoptosis in
      Human Ovarian Cancer Cells.
AB  - BACKGROUND Marsdenia tenacissima extract (MTE) is a traditional Chinese medicine
      that can be effectively used against various cancers. However, to the best of our
      knowledge, its role in ovarian cancer is not known. This study investigated the
      effects of MTE on human ovarian cancer SKOV3 cells. MATERIAL AND METHODS The
      viability and cell cycle of SKOV3 cells were assessed using the cell counting kit
      8 (CCK-8) and propidium Iodide (PI) staining kit, respectively. Cell apoptosis
      and mitochondrial membrane potential (MMP) were detected by flow cytometry. The
      expression levels of proliferation-related and apoptosis-related factors were
      tested by quantitative real-time PCR (qRT-PCR) and Western blot assays,
      respectively. RESULTS We found that MTE markedly reduced the viability of SKOV3
      cells in dose-dependent and time-dependent manners. MTE induced cell cycle arrest
      by downregulating the levels of cyclin D1and cyclin B1. MTE (10, 20, and 40
      mg/mL) markedly increased apoptosis rates (2.77+/-0.6%, 4.95+/-0.97%, and 12.16+/
      0.69%, respectively), and enhanced the loss of MMP. MTE obviously downregulated
      the expression of B cell lymphoma-2 (Bcl-2) and upregulated the expression levels
      of fibroblast-associated (Fas), Fas ligand (FasL), cleaved cysteinyl aspartate
      specific proteinas-3 (caspase-3), and Bcl-2-associated X protein (Bax) compared
      to the control group. In addition, the expressions of phosphorylated mammalian
      target of rapamycin (p-mTOR), phosphorylated protein kinase B (p-AKT), and
      phosphorylated-phosphatidylinositol 3 kinase (p-PI3K) were decreased by MTE.
      CONCLUSIONS MTE inhibited proliferation and induced apoptosis of SKOV3 cells. The
      depression of the PI3K/AKT/mTOR pathway may augment the protective effect of MTE.
      Thus, MTE might be expected to be a new drug for curing ovarian cancer.

PMID- 30196308
TI  - Oxymatrine Inhibits Transforming Growth Factor beta1 (TGF-beta1)-Induced Cardiac
      Fibroblast-to-Myofibroblast Transformation (FMT) by Mediating the Notch Signaling
      Pathway In Vitro.
AB  - BACKGROUND Oxymatrine, a component extracted from the traditional Chinese herb
      Sophora japonica (Sophora flavescens Ait.), has various pharmacological effects,
      especially on the cardiovascular system. However, its cardiac protection effects
      and the underlying mechanism are still poorly understood. In the present study,
      we investigated the inhibitory effect and mechanism of oxymatrine on cardiac
      fibrosis induced by TGF-beta1. MATERIAL AND METHODS Cardiac fibroblasts were
      isolated and purified from neonatal rats. Immunocytochemical staining was used to
      identify the cells. MTT assay and immunofluorescence staining were used to assess
      cardiac fibroblasts proliferation and myofibroblasts transformation. Hematoxylin
      eosin staining was performed to evaluate morphological changes of cardiac
      fibroblasts. The secretion of type I and III collagen was assessed by staining
      with picrosirius red and the hydroxyproline content was determined by
      colorimetric assay. Cardiac fibroblast migration was examined by scratch assay
      and DNA content was detected to analyze cell cycle distribution using flow
      cytometry. Western blot analysis was used to detect the protein expressions of
      Notch pathway-associated protein in cardiac fibroblasts. RESULTS Oxymatrine and
      Notch signaling pathway inhibitor DAPT could attenuated TGF-beta1 induced the
      capacity of proliferation and migration increased in cardiac fibroblasts, as well
      as the secretion of collagen and hydroxyproline colorimetric content in medium.
      TGF-beta1 induced the biomarker alpha-SMA of fibroblast-to-myofibroblast
      transformation (FMT), which was inhibited by oxymatrine and DAPT. Western
      blotting confirmed that oxymatrine blocked the activation of Notch induced by TGF
      beta1. CONCLUSIONS Oxymatrine is a potential inhibitor FMT induced by TGF-beta1,
      which is at least in part mediated via inhibition of Notch signaling.

PMID- 30196310
TI  - Decreased Serum Bilirubin Levels and Increased Uric Acid Levels are Associated
      with Ulcerative Colitis.
AB  - BACKGROUND In recent years, emerging evidence has suggested that ulcerative
      colitis occurs as a consequence of an imbalance between oxidative stress and
      antioxidant capacity. The objective of this study was to investigate whether
      serum total bilirubin and serum uric acid levels were associated with ulcerative
      colitis. MATERIAL AND METHODS We conducted a retrospective case-control study
      which included 170 patients with ulcerative colitis and 200 healthy individuals.
      Concentrations of serum total bilirubin and serum uric acid were obtained from
      biochemical information and segregated into quartiles. Logistic regression
      analysis was adopted to explore the correlations between levels of the 2
      biochemical markers and the risk of ulcerative colitis. RESULTS Compared with
      healthy controls, patients with ulcerative colitis exhibited lower levels of
      serum bilirubin (9.30 umol/L versus 12.49 umol/L respectively, P<0.001).
      Multivariate logistic regression showed that the lowest quartile of total serum
      bilirubin was independently associated with the occurrence of ulcerative colitis
      (OR=2.56, 95%CI: 1.54-4.25, P<0.001). Similarly, ulcerative colitis patients
      exhibited higher concentrations of serum uric acid (338 umol/L versus 300 umol/L
      respectively, P=0.041). Multivariate logistic regression showed that the highest
      quartile of serum uric acid was independently associated with ulcerative colitis
      risk (OR=1.20, 95%CI: 1.05-1.77, P=0.045). Furthermore, a negative association
      was observed between serum total bilirubin and serum uric acid in patients with
      ulcerative colitis. CONCLUSIONS Lower levels of serum total bilirubin and higher
      levels of serum uric acid are associated with ulcerative colitis patients
      compared to healthy controls.

PMID- 30196311
TI  - Neonatal cerebrovascular autoregulation.
AB  - Cerebrovascular pressure autoregulation is the physiologic mechanism that holds
      cerebral blood flow (CBF) relatively constant across changes in cerebral
      perfusion pressure (CPP). Cerebral vasoreactivity refers to the vasoconstriction
      and vasodilation that occur during fluctuations in arterial blood pressure (ABP)
      to maintain autoregulation. These are vital protective mechanisms of the brain.
      Impairments in pressure autoregulation increase the risk of brain injury and
      persistent neurologic disability. Autoregulation may be impaired during various
      neonatal disease states including prematurity, hypoxic-ischemic encephalopathy
      (HIE), intraventricular hemorrhage, congenital cardiac disease, and infants
      requiring extracorporeal membrane oxygenation (ECMO). Because infants are
      exquisitely sensitive to changes in cerebral blood flow (CBF), both hypoperfusion
      and hyperperfusion can cause significant neurologic injury. We will review
      neonatal pressure autoregulation and autoregulation monitoring techniques with a
      focus on brain protection. Current clinical therapies have failed to fully
      prevent permanent brain injuries in neonates. Adjuvant treatments that support
      and optimize autoregulation may improve neurologic outcomes.

PMID- 30196312
TI  - Group-based healthy lifestyle workplace interventions for shift workers: a
      systematic review.
AB  - Objective Shift work is a risk factor for many chronic diseases and has been
      associated with unhealthy lifestyle behaviors. Workplaces have great potential
      for promoting and supporting behavior change. We conducted a systematic review of
      group-based lifestyle workplace interventions for shift workers to (i) identify
      adaptations and intervention components that accommodate shift working and (ii)
      assess their impact on weight, physical activity, sedentary behavior and healthy
      eating. Methods A systematic search was conducted in Scopus, Web of Knowledge,
      EBSCO and Ovid databases. Using pre-established criteria, independent pairs of
      researchers conducted the study selection, quality appraisal and data extraction.
      Results In total, 22 studies on group-based workplace interventions for shift
      workers were included. Many demonstrated organizational level adaptations, such
      as flexible delivery times and paying employees' time for their involvement.
      Delivery locations near the workplace and management support were other key
      features. Common intervention components included competitive group activities,
      individualized goal setting, self-monitoring and feedback, staff involvement in
      intervention delivery, and incentives. There was moderate evidence for
      effectiveness on weight and physical activity outcomes, but insufficient evidence
      for healthy eating outcomes. No interventions focusing on sedentary behavior
      among shift workers were found. Conclusion Current evidence demonstrates that
      group-based workplace interventions can be effective for supporting shift workers
      to lose weight and increase physical activity, while further research is needed
      to change healthy eating and sedentary behaviors. Our findings offer decision
      support on organizational-level adaptations and intervention components that are
      important to make interventions that promote healthy lifestyles more accessible
      to shift workers.

PMID- 30196313
TI  - Alvimopan usage increasing following radical cystectomy.
AB  - PURPOSE: Alvimopan (Entereg), a peripherally acting opioid receptor antagonist,
      is effective in reducing the rate of postoperative ileus and length of hospital
      stay in patients undergoing colorectal surgery, and is now approved for use after
      radical cystectomy (RC). Using data from Vizient (formerly University Health
      System Consortium), we assessed the utilization of alvimopan and its effect on
      perioperative factors after RC. METHODS: The Vizient database, contributed to by
      over 200 US academic hospitals, was evaluated from 2014 to 2016. Patients who had
      undergone radical cystectomy were included. Alvimopan exposure and postoperative
      outcomes were collected. RESULTS: 7472 patients underwent cystectomy in the 3
      years examined, with 3391 (45.4%) patients receiving alvimopan over this time
      period. The use of alvimopan increased from 35 to 59%. The receipt of alvimopan
      was associated with a decrease in perioperative morbidity (10.53% vs 19.23%, p =
      0.027). CONCLUSION: This study, the largest to examine the real-world utilization
      of alvimopan since FDA approval for RC, shows that alvimopan utilization has
      increased substantially and is associated with reduced perioperative morbidity in
      patients undergoing cystectomy.

PMID- 30196314
TI  - Microbiome Diversity in Cotton Rhizosphere Under Normal and Drought Conditions.
AB  - Climate change contributes to drought stress and subsequently affects crop
      growth, development, and yield. The microbial community, such as fungi and
      bacteria in the rhizosphere, is of special importance to plant productivity. In
      this study, soil collected from a cotton research field was used to grow cotton
      plants (Gossypium hirsutum cv. Jin668) under controlled environment conditions.
      Drought stress was applied at flowering stage, while control plants were
      regularly watered. At the same time, the soil without plants was also subjected
      to drought, while control pots were regularly watered. The soil was collected in
      sterilized tubes and microbial DNA was isolated and high-throughput sequencing of
      16S rRNA genes was carried out. The alpha diversity of bacteria community
      significantly increased in the soil with cotton plants compared to the soil
      without cotton plants. Taxonomic analysis revealed that the bacterial community
      structure of the cotton rhizosphere predominantly consisted of the phyla
      Proteobacteria (31.7%), Actinobacteria (29.6%), Gemmatimonadetes (9.8%),
      Chloroflexi (9%), Cyanobacteria (5.6%), and Acidobacteria. In the drought-treated
      rhizosphere, Chloroflexi and Gemmatimonadetes were the dominant phyla. This study
      reveals that the cotton rhizosphere has a rich pool of bacterial communities even
      under drought stress, and which may improve drought tolerance in plants. These
      data will underpin future improvement of drought tolerance of cotton via the soil
      microbial community.

PMID- 30196315
TI  - Correction to: Tetraspanin-enriched microdomains regulate digitation junctions.
AB  - In the original publication, abstract text, one of the co-author's name and the
      legend to Table 1 were incorrectly published.

PMID- 30196316
TI  - Cellular localization and regulation of receptors and enzymes of the
      endocannabinoid system in intestinal and systemic inflammation.
AB  - Surveys suggest that Cannabis provides benefit for people with inflammatory bowel
      disease. However, mechanisms underlying beneficial effects are not clear. We
      performed in situ hybridization RNAscope(r) combined with immunohistochemistry to
      show cell-specific distribution and regulation of cannabinoid receptor 1 and 2
      (CB1, CB2), G protein-coupled receptor 55 (GPR55), and monoacylglycerol lipase
      (MGL) mRNA in immune cells using murine models of intestinal and systemic
      inflammation. In healthy animals, the presence in enteric ganglia is high for CB1
      mRNA, but low for CB2 and GPR55 mRNAs. MGL mRNA is predominant throughout the
      intestinal wall including myenteric neurons, epithelium, circular and
      longitudinal muscular layers, and the lamina propria. Within the immune system,
      B220+ cells exhibit high gene expression for CB2 while the expression of CB2 in
      F4/80+ and CD3+ cells is less prominent. In contrast, GPR55 mRNA is highly
      present in F4/80+ and CD3+ cells. qRT-PCR of total colonic segments shows that
      the expression of GPR55 and MGL genes drops during intestinal inflammation. Also
      at cellular levels, GPR55 and MGL gene expression is reduced in F4/80+, but not
      CD3+ cells. As to systemic inflammation, reduced gene expression of MGL is
      observed in ileum by qRT-PCR, while at cellular levels, altered gene expression
      is also seen for CB1 and GPR55 in CD3+ but not F4/80+ cells. In summary, our
      study reveals changes in gene expression of members of the endocannabinoid system
      in situ attesting particularly GPR55 and MGL a distinct cellular role in the
      regulation of the immune response to intestinal and systemic inflammation.

PMID- 30196317
TI  - Definition, symptoms and risk of techno-stress: a systematic review.
AB  - PURPOSE: Techno-stress (TS) is an emergent phenomenon closely related to the
      pervasive use of information and communication technologies in modern society.
      Despite numerous studies existing in the literature, only few comprehensive
      reviews have been performed, which has led to fragmented information about TS.
      This systematic review aimed to clarify the definition, the symptoms, and the
      risk factors of TS, focusing on the differences between work-related and non-work
      related sources of TS. METHODS: A comprehensive literature review of three
      electronic databases was performed according to the PRISMA statement.
      'Technostress' was used as the only keyword. RESULTS: In the qualitative
      synthesis, 105 studies were included: 84 cross-sectional studies, 8 experimental
      studies and 13 reviews (11 narrative and 2 systematic reviews). 70 studies (67%)
      addressed work-related TS, 26 (25%) addressed non-work-related TS, while 8 (8%)
      did not differentiate between work and non-work fields. The presence and level of
      TS among individuals was described in 38 studies (29%), whilst the techno
      stressors, and the consequences of TS, were described in 53 studies (51%). The
      antecedents of TS were reported in 47 studies (45%), its moderators in 40 studies
      (38%), whilst its symptoms in only 11 studies (10%). CONCLUSIONS: TS affects both
      professional and private life. It can determine a reduction in job and life
      satisfaction and in productivity, and is often associated to the occurrence of
      psychological and behavioral disorders. Efforts should be made to recognize
      situations with a high risk of causing TS, to prevent its progressive development
      in a prospective way using mainly cohort studies.

PMID- 30196318
TI  - Distinguishing groups and exploring health differences among multiple job holders
      aged 45 years and older.
AB  - PURPOSE: To identify distinct groups of older multiple job holders and to explore
      health differences between these groups. METHODS: We selected respondents from
      STREAM, a Dutch cohort study among persons aged 45 years and older, who reported
      having multiple jobs (N = 702). We applied latent class analysis to identify
      groups of multiple job holders. The association between these groups and health,
      measured with the SF-12, was studied cross-sectionally and longitudinally (1 year
      of follow-up), using linear regression analyses. RESULTS: Four groups of older
      multiple job holders were identified: (1) a vulnerable group (N = 145), who
      preferred having one job, and had jobs with high demands and low resources; (2)
      an indifferent group (N = 134), who did not experience many benefits or
      disadvantages of multiple job holding (MJH); (3) a satisfied hybrid group, who
      were all self-employed in their second job (N = 310); and (4) a satisfied
      combination group, who all had a second job as an employee (N = 113). Both the
      satisfied hybrid and satisfied combination groups preferred MJH and experienced
      benefits of it. At baseline, the vulnerable group experienced significantly lower
      physical and mental health than the other groups. We found no significant
      differences regarding changes in health after 1 year. CONCLUSIONS: Four groups of
      older multiple job holders could be distinguished. The vulnerable group
      experienced lower physical and mental health at baseline than the other three
      groups. Policies and interventions supporting vulnerable multiple job holders may
      need to be developed. Future research is recommended to take heterogeneity among
      multiple job holders into account.

PMID- 30196319
TI  - Investigating effects of climate change, urbanization, and sea level changes on
      groundwater resources in a coastal aquifer: an integrated assessment.
AB  - Urbanization and climate change are causing numerous side effects on groundwater
      resources. In this study, an integrated modeling approach by linking soil and
      water application tool (SWAT), modular finite difference groundwater flow
      (MODFLOW), and three-dimensional variable-density groundwater flow coupled with
      multi-species solute and heat transport (SEAWAT) models were used to exhibit
      responses of groundwater systems, in terms of flow and salt concentrations to
      current and future climatic and anthropogenic changes. Future climate scenarios
      for periods of 2010-2040 were generated from the Canadian Global Coupled Model
      (CGCM) for scenarios A1B, B1, and A2 which was downscaled by the Long Ashton
      Research Station weather generator (LARS-WG) providing precipitation and
      temperature patterns for the period 2018-2040. The GCM's outputs were applied to
      SWAT model to estimate recharge rate for the ten scenarios designed to assess the
      sensitivity of the aquifer to urbanization and climate change. The estimated
      recharge rate from SWAT was utilized as an input in numerical groundwater model
      to evaluate saltwater intrusion (SWI), changes in freshwater storage within the
      aquifer system, and changes in groundwater level. Based on the results of each
      scenario's simulation, increase of pumping rate yield by future population growth
      will have more adverse effects on the unconfined aquifer. The derived information
      from this study can be used to improve future works by developing a better
      understanding of the managed and unmanaged response of freshwater storage and
      unconfined groundwater systems to climate change and anthropogenic activities.

PMID- 30196320
TI  - Evaluation of susceptibility of HIV-1 CRF01_AE variants to neutralization by a
      panel of broadly neutralizing antibodies.
AB  - Broadly neutralizing antibodies (bNAbs) are very promising agents for HIV-1
      prophylaxis and AIDS treatment. However, the neutralization susceptibility of
      circulating recombinants such as CRF01_AE, which is becoming increasingly
      prevalent, has not been studied in detail until now. Here, we focused on CRF01_AE
      in China and aimed to find bNAbs that can be used for neutralization of CRF01_AE.
      Full-length env clones were obtained from the plasma samples of 22 HIV-1-infected
      individuals sampled in 2009 and 2015. An env-pseudovirus-based neutralization
      assay was conducted using five categories of bNAbs: VRC01, NIH45-46G54W, and
      3BNC117 (targeting the CD4 binding site); PG9 and PG16 (targeting the V1V2 loop);
      2G12 (glycan specific), PGT121 and 10-1074 (targeting the V3 glycan); 2F5, 4E10,
      and 10E8 (targeting the membrane-proximal external region (MPER)). The
      neutralizing efficiency was compared, and features of the escape pseudoviruses
      were analyzed. The CRF01_AE pseudoviruses exhibited different susceptibility to
      these bNAbs. Overall, 4E10, 10E8, and 3BNC117 neutralized all 22 env-pseudotyped
      viruses, followed by NIH45-46G54W and VRC01, which neutralized more than 90% of
      the viruses. 2F5, PG9, and PG16 showed only moderate breadth, while the other
      three bNAbs neutralized none of these pseudoviruses. Specifically, 10E8, NIH45
      46G54Wand 3BNC117 showed the highest efficiency, combining neutralization potency
      and breadth. Mutations at position 160, 169, 171 were associated with resistance
      to PG9 and PG16, while loss of a potential glycan at position 332 conferred
      insensitivity to V3-glycan-targeting bNAbs. Our results may help for choosing
      bNAbs that can be used preferentially for prophylactic or therapeutic approaches
      in China.

PMID- 30196321
TI  - Correction to: Description of a new species Physaloptera goytaca n. sp.
      (Nematoda, Physalopteridae) from Cerradomys goytaca Tavares, Pessoa & Goncalves,
      2011 (Rodentia, Cricetidae) from Brazil.
AB  - The name of Luanna Castro Oliveira was incorrectly spelled as Luana Castro
      Oliveira in the original version of this article.

PMID- 30196322
TI  - Filarial nematode (order: Spirurida) surveillance in urban habitats, in the city
      of Pecs (Hungary).
AB  - As part of the seasonal mosquito control activities in the city of Pecs (Baranya
      County, Hungary), a total of 1123 adult female mosquitoes belonging to 18 species
      (including the invasive species Aedes koreicus) were collected from human
      inhabited areas, using CO2-baited traps, during two consecutive years. To survey
      the presence and prevalence of filarial parasites in these mosquitoes, we
      performed a molecular survey for filarial DNA, attempted by PCR using generic
      primers (COI), and followed by DNA sequencing. Filaroid nematode DNA was detected
      in 4% of investigated mosquito pools. Out of 410 pools, 9 pools of mosquitoes
      were positive for Dirofilaria repens (Aedes vexans, Aedes koreicus,
      Coquillettidia richiardii), and/or Dirofilaria immitis (Ae. vexans, Cq.
      richiardii), and further 8 pools were positive for Setaria tundra (Ae. vexans,
      Cq. richiardii). Our study provides novel insight for prevalence of filaroid
      nematodes in mosquitoes occurring in close proximity to humans, thereby
      highlights the possible human and veterinary health importance of these mosquito
      species, including the recently introduced invasive mosquito Ae. koreicus.

PMID- 30196323
TI  - Febuxostat in the treatment of gout patients with low serum uric acid level: 1
      year finding of efficacy and safety study.
AB  - To retrospectively analyze the efficacy and safety of febuxostat on gout patients
      with low serum uric acid level. A study was conducted in Nanjing First Hospital
      from October 2015 to September 2016. Thirty nine acute gouty arthritis patients
      from the emergency and outpatient department were included. Patients met the 2015
      Gout Classification Criteria revised by American College of Rheumatology/European
      League Against Rheumatism (ACR/EULAR) and had urate deposition around the joints
      detected by dual-energy computerized tomography (DECT). Patients whose serum uric
      acid (SUA) were between 5.0 and 7.0 mg/dl (300-420 MUmol/l) received febuxostat
      treatment to maintain the SUA level between 3.0 and 5.0 mg/dl for 1 year.
      Efficacy and safety of febuxostat were observed during the process. Three of 39
      subjects were excluded because of adverse events (AEs) after receiving an initial
      febuxostat treatment for 2 months. Thirty six subjects were enrolled. The mean
      SUA level was reduced significantly from 6.51 +/- 0.28 mg/dl at baseline to 4.24
      +/- 0.38 mg/dl and SUA of all subjects decreased by 34.8% compared with baseline.
      After 1-year treatment, the volume of tophus was reduced approximately 62.8%.
      Serum creatinine decreased stepwise in 8 gout patients with chronic kidney
      diseases from 162.5 +/- 9.2 MUmol/l to 131.4 +/- 11.0 MUmol/l. Two months after
      initiation of treatment, the number of gout flares began to markedly decrease and
      almost did not occur after 1 year. After the 1-year treatment of febuxostat, the
      average SUA level declined significantly, and the renal function improved
      gradually. There was nearly complete abolition of gout flares by the end of the
      study. Tophi resolved markedly compared with baseline as assessed by DECT.
      Furthermore, only a few people experienced adverse events. Febuxostat has a
      notable effect for gout patients in the lower SUA level range.

PMID- 30196324
TI  - Sensor-based gait analysis of individualized improvement during apomorphine
      titration in Parkinson's disease.
AB  - Mobile, sensor-based gait analysis in Parkinson's disease (PD) facilitates the
      objective measurement of gait parameters in cross-sectional studies. Besides
      becoming outcome measures for clinical studies, the application of gait
      parameters in personalized clinical decision support is limited. Therefore, the
      aim of this study was to evaluate whether the individual response of PD patients
      to dopaminergic treatment may be measured by sensor-based gait analysis. 13 PD
      patients received apomorphine every 15 min to incrementally increase the
      bioavailable apomorphine dose. Motor performance (UPDRS III) was assessed 10 min
      after each apomorphine injection. Gait parameters were obtained after each UPDRS
      III rating from a 2 * 10 m gait sequence, providing 41.2 +/- 9.2 strides per
      patient and injection. Gait parameters and UPDRS III ratings were compared cross
      sectionally after apomorphine titration, and more importantly between consecutive
      injections for each patient individually. For the individual response, the effect
      size Cohen's d for gait parameter changes was calculated based on the stride
      variations of each gait sequence after each injection. Cross-sectionally,
      apomorphine improved stride speed, length, gait velocity, maximum toe clearance,
      and toe off angle. Between injections, the effect size for individual changes in
      stride speed, length, and maximum toe clearance correlated to the motor
      improvement in each patient. In addition, significant changes of stride length
      between injections were significantly associated with UPDRS III improvements. We
      therefore show, that sensor-based gait analysis provides objective gait
      parameters that support clinical assessment of individual PD patients during
      dopaminergic treatment. We propose clinically relevant instrumented gait
      parameters for treatment studies and especially clinical care.

PMID- 30196325
TI  - Treatment course and outcomes after revascularization surgery for moyamoya
      disease in adults.
AB  - BACKGROUND: International trials suggest benefit of revascularization surgery
      (RS) for moyamoya disease (MMD). However, nationally representative US data on
      demographics and outcomes after RS in MMD are lacking. AIMS: To estimate causes
      and rates of readmission after RS for MMD. METHODS: In the Nationwide
      Readmissions Database, index admissions for ECICB for MMD and readmissions for
      ischemic stroke (IS), subarachnoid hemorrhage (SAH), and intracerebral hemorrhage
      (ICH) were identified using validated International Classification of Diseases,
      Ninth Revision, Clinical Modification codes. We summarized demographics and
      comorbidities, and calculated 30-, 60-, and 90-day readmission rates per 100,000
      index admissions. RESULTS: Among 201 index admissions for RS for MMD, mean age
      (SD) was 41.7 (12.6) years; 75% were female; 24% had diabetes; 53% had
      hypertension; 40% had hypercholesterolemia; 3% had ICH; 16% had IS; and 1% had
      SAH. RS was performed at large hospitals in 83%, urban hospitals in 85%, and
      teaching hospitals in 97%. 80% were discharged home. 34% had a readmission during
      follow-up. Leading reasons for readmission up to 90 days included MMD (62%),
      postoperative infection (10%), sickle cell crisis (4%), ischemic stroke (4%),
      epilepsy (2%), subdural hemorrhage (2%) and headache (2%). Readmission rates (per
      100,000 index admissions) were 559 at 30 days, 1829 at 60 days, and 2027 at 90
      days for IS. There were no readmissions for SAH or ICH. CONCLUSIONS: This
      analysis of nationally representative US data suggests that although readmission
      after RS for MMD is not uncommon, cerebral hemorrhagic events during the 90-day
      postoperative period are rare.

PMID- 30196326
TI  - The effect of a single botulinum toxin treatment on somatosensory processing in
      idiopathic isolated cervical dystonia: an observational study.
AB  - BACKGROUND: Patients with idiopathic cervical dystonia (CD) experience
      involuntary neck muscle contractions, abnormal head position and pain accompanied
      by dysfunctions in somatosensory processes such as postural control, cervical
      sensorimotor and perception of visual verticality. First-line treatment is
      injection with botulinum toxin (BoNT). It remains unclear whether this affects
      sensorimotor processes. AIM: To investigate the effect of first-line care on
      deficiencies in somatosensory processes. METHODS: In this observational study, 24
      adult patients with idiopathic CD were assessed three times over a treatment
      period of 12 weeks following a single treatment with BoNT. Disease severity was
      assessed by a disease-specific questionnaire, rating scale and the visual
      analogue scale. Seated postural control was assessed with posturography, cervical
      sensorimotor control was assessed by the joint repositioning error with an eight
      camera infrared motion analysis system during a head repositioning accuracy test
      and perception of visual verticality was assessed with the subjective visual
      vertical test. RESULTS: Disease symptoms significantly improved following BoNT
      injections and deteriorated again at 12 weeks. This improvement was not
      accompanied by improved postural control, cervical sensorimotor control and
      perception of visual verticality. A trend toward improvement was seen; however,
      it did not reach the level of the control population. CONCLUSION: The peripheral
      and central treatment effects of BoNT have little to no effect on postural and
      cervical sensorimotor control in CD. Further research may explore whether sensory
      training or specialized exercise therapy improves somatosensory integration and
      everyday functioning in patients with CD.

PMID- 30196327
TI  - 2017 revisions of McDonald criteria shorten the time to diagnosis of multiple
      sclerosis in clinically isolated syndromes.
AB  - OBJECTIVES: To investigate the impact of the 2017 revisions of McDonald criteria
      on the diagnosis of multiple sclerosis (MS) in a cohort of patients with
      clinically isolated syndrome (CIS) and dissemination in space (DIS) of
      demyelinating lesions. METHODS: We retrospectively analyzed 137 patients with CIS
      + DIS from two Italian MS centers. RESULTS: Application of the 2017 revisions of
      McDonald criteria in our cohort led to a diagnosis of MS in 82.5% of the patients
      who could have not been diagnosed with MS according to the previous criteria at
      the time of the first demyelinating event. After a follow-up of 3.8 +/- 2.9
      years, 85.8% of these patients eventually satisfied also the previous (2010)
      criteria. CONCLUSIONS: Application of the 2017 revisions of McDonald criteria
      results in an earlier diagnosis of MS in a large percentage of CIS patients
      destined to convert to MS.

PMID- 30196328
TI  - Production of alpha-linolenic acid in Yarrowia lipolytica using low-temperature
      fermentation.
AB  - alpha-Linolenic acid (ALA) is an essential omega-3 fatty with reported health
      benefits. However, this molecule is naturally found in plants such as flaxseed
      and canola which currently limits production. Here, we demonstrate the potential
      to sustainably produce ALA using the oleaginous yeast Yarrowia lipolytica.
      Through the use of a recently identified Delta12-15 desaturase (Rk Delta12-15),
      we were able to enable production in Y. lipolytica. When combined with a
      previously engineered lipid-overproducing strain with high precursor
      availability, further improvements of ALA production were achieved. Finally, the
      cultivation of this strain at lower temperatures significantly increased ALA
      content, with cells fermented at 20  degrees C accumulating nearly 30% ALA of the
      total lipids in this cell. This low-temperature fermentation represents improved
      ALA titer up to 3.2-fold compared to standard growth conditions. Scale-up into a
      fed-batch bioreactor produced ALA at 1.4 g/L, representing the highest published
      titer of this omega-3 fatty acid in a yeast host.

PMID- 30196329
TI  - Endo-xylanases as tools for production of substituted xylooligosaccharides with
      prebiotic properties.
AB  - Xylan has a main chain consisting of beta-1,4-linked xylose residues with diverse
      substituents. Endoxylanases cleave the xylan chain at cleavage sites determined
      by the substitution pattern and thus give different oligosaccharide product
      patterns. Most known endoxylanases belong to glycoside hydrolase (GH) families 10
      and 11. These enzymes work well on unsubstituted xylan but accept substituents in
      certain subsites. The GH11 enzymes are more restricted by substituents, but on
      the other hand, they are normally more active than the GH10 enzymes on insoluble
      substrates, because of their smaller size. GH5 endoxylanases accept arabinose
      substituents in several subsites and require it in the - 1 subsite. This
      specificity makes the GH5 endoxylanases very useful for degradation of highly
      arabinose-substituted xylans and for the selective production of
      arabinoxylooligosaccharides, without formation of unsubstituted
      xylooligosaccharides. The GH30 endoxylanases have a related type of specificity
      in that they require a uronic acid substituent in the - 2 subsite, which makes
      them very useful for the production of uronic acid substituted oligosaccharides.
      The ability of dietary xylooligosaccharides to function as prebiotics in humans
      is governed by their substitution patterns. Endoxylanases are thus excellent
      tools to tailor prebiotic oligosaccharides to stimulate various types of
      intestinal bacteria and to cause fermentation in different parts of the
      gastrointestinal tract. Continuously increasing knowledge on the function of the
      gut microbiota and discoveries of novel endoxylanases increase the possibilities
      to achieve health-promoting effects.

PMID- 30196330
TI  - A gestural repertoire of 1- to 2-year-old human children: in search of the ape
      gestures.
AB  - When we compare human gestures to those of other apes, it looks at first like
      there is nothing much to compare at all. In adult humans, gestures are thought to
      be a window into the thought processes accompanying language, and sign languages
      are equal to spoken language with all of its features. Some research firmly
      emphasises the differences between human gestures and those of other apes;
      however, the question about whether there are any commonalities is rarely
      investigated, and has mostly been confined to pointing gestures. The gestural
      repertoires of nonhuman ape species have been carefully studied and described
      with regard to their form and function-but similar approaches are much rarer in
      the study of human gestures. This paper applies the methodology commonly used in
      the study of nonhuman ape gestures to the gestural communication of human
      children in their second year of life. We recorded (n = 13) children's gestures
      in a natural setting with peers and caregivers in Germany and Uganda. Children
      employed 52 distinct gestures, 46 (89%) of which are present in the chimpanzee
      repertoire. Like chimpanzees, they used them both singly, and in sequences, and
      employed individual gestures flexibly towards different goals.

PMID- 30196331
TI  - Plant metabolic engineering in the synthetic biology era: plant chassis
      selection.

PMID- 30196332
TI  - HIV Disclosure Among Pregnant Women Initiating ART in Cape Town, South Africa:
      Qualitative Perspectives During the Pregnancy and Postpartum Periods.
AB  - For women enrolled in prevention of mother-to-child transmission (PMTCT)
      programs, non-disclosure of their HIV status can be a significant barrier to
      sustained HIV care engagement. To explore decision-making surrounding HIV
      disclosure among HIV-infected pregnant women, we conducted repeated in-depth
      interviews during pregnancy and postpartum with 20 women recruited from a PMTCT
      clinic in Cape Town, South Africa. Three domains were examined using thematic
      analysis: (1) disclosure experiences, (2) challenges associated with partner
      disclosure, and (3) implications of nondisclosure. All women had disclosed to
      someone by the time of the baby's birth, typically limiting their disclosure to
      trusted individuals. Only half of participants disclosed to the father of the
      child. Nondisclosure, particularly to partners, was a significant source of worry
      and stress. Women used pregnancy as an explanation for using medication and
      attending frequent clinic appointments, and recognized impending challenges in
      the postpartum period when this excuse would no longer apply. Results suggest
      that PMTCT programs have a key role to play in helping individuals to make
      decisions about HIV disclosure, and assisting patients to navigate the disclosure
      process, especially with partners.

PMID- 30196333
TI  - Working Below Skill Level as Risk Factor for Distress Among Latin American
      Migrants Living in Germany: A Cross-Sectional Study.
AB  - About 84,710 Latin American migrants currently live in Germany. Knowledge about
      their work situation in relation to their skill level and its association with
      mental health is limited. Therefore, the aims of this study were to assess the
      prevalence of working below skill level and its association with the prevalence
      of distress in Latin Americans living in Germany. This cross-sectional study
      included a convenience sample of 282 Latin American migrants living in Germany.
      Participants were recruited by a short online (Facebook, personal contacts) or
      interview-based questionnaire from November 2015 to April 2016. Questions
      included skill level, job category (categorized by ISCO 2008 code), socio
      demographics, violence at the workplace and distress. The latter was assessed by
      Goldberg's General Health Questionnaire using a cut-off of 4/5. Descriptive
      statistics were followed by logistic regression analyses adjusting for potential
      confounders. About half of the study population reported symptoms of distress
      (45%). 63% of the population worked below skill level. 12-months prevalence of
      violence at the workplace was 14%. After adjustment, working below skill level
      was statistically significantly related to distress (odds ratio 2.80; 95%
      confidence interval 1.58-4.95). Working below skill level is common in Latin
      American migrants in Germany and may result in poor psychosocial well-being.

PMID- 30196334
TI  - Abdominal obesity, glucose intolerance and decreased high-density lipoprotein
      cholesterol as components of the metabolic syndrome are associated with the
      development of colorectal cancer.
AB  - Metabolic syndrome (MetS) and its components has been thought to be involved in
      the development of colorectal cancer (CRC). However, the results is often
      inconsistent according to gender or anatomical location of tumor. This study
      aimed to investigate the association between MetS and its components and CRC
      development by gender and tumor location. We evaluated the data of 22,809,722
      Korean individuals of the National semi-compulsive cohort who underwent regular
      health check-ups between 2009 and 2012. Compared to subjects without MetS
      components, the hazard ratio for CRC development in patients with MetS was 1.22
      (95% Confidence Interval [CI] 1.20-1.24) and this association was more prominent
      in men than in women (HR 1.41 95% CI 1.37-1.44 vs. HR 1.23 95% CI 1.20-1.27, P
      for interaction < 0.001). Left-sided colon cancers were more associated with MetS
      among men compared to women (HR 1.70, 95% CI 1.61-1.80 vs. HR 1.43, 95% CI 1.33
      1.54), while right colon cancers showed a stronger association with MetS among
      women than men (HR 1.63, 95% CI 1.49-1.78 vs. HR 1.34, 95% CI 1.24-1.44) (all P
      for interaction < 0.001, respectively). Having two MetS components was still
      associated with CRC development and the association was the highest when two of
      glucose intolerance, abdominal obesity and low high-density lipoprotein
      cholesterol (HDL-C) combined. Individuals with glucose intolerance, abdominal
      obesity or low HDL-C levels, may need to undergo thorough screening for CRC even
      if they do not meet the diagnostic MetS criteria.

PMID- 30196335
TI  - Mitochondrial targeting domain of NOXA causes necrosis in apoptosis-resistant
      tumor cells.
AB  - The resistance of tumor cells to apoptosis-inducing anticancer agents is regarded
      as a major impediment for the treatment of cancer patients. This study aimed to
      examine the possibility whether a necrosis-inducing peptide containing the
      mitochondria-targeting domain (MTD) of NOXA kills tumor cells that are resistant
      to apoptosis-inducing anticancer agents. To examine this possibility, we
      established doxorubicin-resistant (Dox-Res) cells by treating CT26 cells with
      increasing amounts of doxorubicin. The apoptosis resistance of the Dox-Res CT26
      cells was confirmed by measuring the cell viability and activation of caspases.
      We showed that the MTD-containing peptide fused to eight arginine residues
      (R8:MTD), a necrosis-inducing peptide, induced necrosis in the Dox-Res CT26
      cells, together with a cytosolic calcium spike, reactive oxygen species
      production, and the release of high mobility group box 1 into the media.
      Moreover, we demonstrated the killing effect of R8:MTD in tumor tissues generated
      using the Dox-Res CT26 cells in a mouse model. Therefore, our results suggest
      that MTD-containing peptides may provide an alternative tool for the elimination
      of relapsed tumor cells that are not responsive to apoptosis-inducing anticancer
      agents.

PMID- 30196336
TI  - Elucidating the mechanism governing cell rotation under DEP using the volumetric
      polarization and integration method.
AB  - Cell rotation can be achieved by utilizing rotating electric fields through which
      torques are generated due to phase difference between the dipole moment of cells
      and the external electric field. While reports of cell rotation under non
      rotating electrical fields, such as dielectrophoresis (DEP), are abound, the
      underlying mechanism is not fully understood. Because of this, contradicting
      arguments remain regarding if a single cell can rotate under conventional DEP.
      What's more, the current prevailing DEP theory is not adequate for identifying
      the cause for such disagreements. In this work we applied our recently developed
      Volumetric Polarization and Integration (VPI) method to investigate the possible
      causes for cell rotation under conventional DEP. Three-dimensional (3D) computer
      models dealing with a cell in a DEP environment were developed to quantify the
      force and torque imparted on the cell by the external DEP field using COMSOL
      Multiphysics software. Modeling results suggest that eccentric inclusions with
      low conductivity inside the cell will generate torques (either in clockwise or
      counter-clockwise directions) sufficient to cause cell rotation under DEP. For
      validation of modeling predictions, experiments with rat adipose stem cells
      containing large lipid droplets were conducted. Good agreement between our
      modeling and experimental results suggests that the VPI method is powerful in
      elucidating the underlying mechanisms governing the complicated DEP phenomena.

PMID- 30196337
TI  - Comparative analysis of surgical processes for image-guided endoscopic sinus
      surgery.
AB  - PURPOSE: This study proposes a method to analyze surgical performance by
      modeling, aligning, and comparing surgical processes. This method is intended to
      serve as a means to support the enhancement of surgical skills for endoscopic
      sinus surgeries (ESSs). We focus on surgical navigation systems used in image
      guided ESSs and aim to construct a comparative analysis method for surgical
      processes based on the information about the surgical instruments motion obtained
      from the navigation system. METHODS: The proposed method consists of the
      following three parts: quantification of surgical features, modeling of surgical
      processes, and alignment and comparison of surgical process models (SPMs). First,
      we defined time-series parameters using the navigation-based surgical data.
      Second, we created SPMs by applying the defined parameters and the relative
      positional information of the instruments to the patient's anatomy. Third, we
      constructed a method to align and compare SPMs based on dynamic time warping with
      barycenter averaging. RESULTS: The proposed method was validated on a dataset
      containing surgical data obtained by an optical tracking system from 14 clinical
      ESS cases. We evaluated the validity of the comparative analysis by aligning and
      comparing SPMs between experts and residents. The validation results suggested
      that the proposed method could achieve proper alignment of the SPMs and clarify
      the differences in surgical processes between experts and residents. CONCLUSION:
      We developed a method to enable a time-series comparative analysis of surgical
      processes based on the surgical data from the navigation system. This method can
      allow surgeons to identify differences between their procedures and reference
      procedures such as experts' procedures.

PMID- 30196339
TI  - Meaning-making and quality of life in heart failure interventions: a systematic
      review.
AB  - PURPOSE: Heart failure (HF) patients often report high levels of psychological
      distress and diminished quality of life (QoL). As such, interventions aimed at
      improving their QoL and other positive psychosocial outcomes are needed. Some
      interventions have shown promise, but results are mixed. Interventions directed
      toward physical well-being (e.g., self-care behaviors, medical adherence) may be
      less effective at improving QoL than those aimed at improving psychological well
      being (e.g., stress reduction, coping strategies). We systematically reviewed
      recent HF interventions and compared results of those emphasizing coping
      strategies related to meaning-making to those lacking meaning-making components
      as a possible factor in QoL discrepancies. METHODS: A systematic review of four
      databases produced 439 studies for potential inclusion, of which 25 qualified for
      review. These were coded into substantial or minimal meaning focus. RESULTS:
      Forty percent of all studies (n = 10) reported improved QoL due to intervention
      effects, while 60% reported no significant change in QoL (60%; n = 15). Fewer
      than one-third of minimal meaning focus studies demonstrated significant
      improvements in QoL (30.8%; n = 4). In contrast, half of substantial meaning
      focus studies demonstrated significant improvements in QoL (50%; n = 6).
      CONCLUSIONS: By clarifying the potential importance of promoting meaning-making
      in improving QoL of HF patients, we highlight its potential value in future
      interventions directed to this underserved, high-risk patient population.

PMID- 30196342
TI  - 25th Annual Conference of the International Society for Quality of Life Research.

PMID- 30196340
TI  - Population health status based on the EQ-5D-Y-3L among adolescents in Sweden:
      Results by sociodemographic factors and self-reported comorbidity.
AB  - PURPOSE: The EQ-5D-Y-3L is a generic health-related quality of life (HRQoL)
      measure developed for youth from 8 years old. The aim of this study is to present
      population health status, based on the EQ-5D-Y-3L, among adolescents in Sweden,
      by sex, age, self-reported comorbidity and parents' occupational status. METHODS:
      Data were obtained from a cross-sectional total survey among students, aged 13-18
      years, in a Swedish County year 2014. The survey included EQ-5D-Y-3L, questions
      regarding self-reported health, disease, functional impairment and mental
      distress. Parents' occupational status was used as a proxy for socio-economic
      status. RESULTS: A total of 6574 participants answered all the EQ-5D-Y-3L
      dimensions (mean age was 15.9 years, same proportion of boys and girls). Girls
      reported more problems than boys in the dimensions 'doing usual activities',
      'having pain or discomfort' and 'feeling worried, sad or unhappy', and lower mean
      VAS score. Respondents with one or both parents unemployed reported more problems
      with usual activities, pain/discomfort and in the mood dimension than those with
      both parents employed. Those with comorbidity had in general more problems in all
      dimensions and lower mean VAS score. The highest impact on VAS score was found
      for adolescents who reported that they always felt depressed. CONCLUSIONS: Sex,
      age, self-reported comorbidity and parents' occupational status were associated
      with HRQoL determined by the EQ-5D-Y-3L in the general population of adolescents.
      The ability of EQ-5D-Y-3L to distinguish adolescents' health status based on
      these factors confirms the instrument's usefulness in assessment of HRQoL and as
      guidance for prioritization.

PMID- 30196343
TI  - Drug interaction as a predictor of direct oral anticoagulant drug levels in
      atrial fibrillation patients.
AB  - Data are limited on the effects of drug interactions on direct-acting oral
      anticoagulant (DOAC) levels. We evaluated the effects of the use of interacting
      drugs on DOAC levels in patients with atrial fibrillation (AF). We reviewed data
      of AF patients tested for DOAC levels in 2013-2017. The primary outcomes were
      drug levels exceeding the expected steady-state range, and in the highest
      quartile. A multivariate analysis was performed to evaluate the correlation of
      treatment by the use of interacting drugs, CYP3A4 and P-glycoprotein (P-gp)
      inhibitors, with the primary outcomes. Overall, 147 patients underwent DOAC level
      measurement [dabigatran (n = 31), rivaroxaban (n = 29), apixaban (n = 87)].
      Thirty-three (22.4%) had drug levels exceeding the expected range. Seventy-nine
      (53.7%) patients were treated with at least one interacting drug. In multivariate
      analysis, the concomitant use of interacting drugs was an independent predictor
      for drug levels exceeding the expected range (OR 3.3, 95% CI 1.20-9.05). The
      defined daily dose of the interacting drug correlated positively with DOAC levels
      (r = 0.29, P = 0.001). Co-treatment with interacting drugs was associated with
      extremely high levels of dabigatran, (OR 16.6, 95% CI 1.29-215.18) but not of the
      other DOAC examined. Concomitant use of interacting drugs is associated with high
      DOAC levels in patients with AF. Further investigation is warranted to establish
      the differences between specific DOAC, evaluate the effect on patient outcomes,
      and characterize the role of DOAC monitoring in this setting.

PMID- 30196345
TI  - Massive juvenile polyposis of the stomach in a family with SMAD4 gene mutation.
AB  - Relatively little is known on the genotype-phenotype correlations between SMAD4
      gene mutations, juvenile polyposis of the intestine and Hereditary Hemorrhagic
      Teleangectasia. We describe a family in which the proband (a 46-year old woman)
      had massive polyposis of the stomach-leading to surgery-with high-grade dysplasia
      at histology. Molecular analysis was carried out using Next Generation sequencing
      techniques with Miseq Illumina Platforms and a minimal coverage of 40 reads. In
      the proband, the analysis showed the presence of a truncating mutation in the
      SMAD4 gene (c.1213dupC, a variant previously associated with juvenile polyposis
      and Hereditary Hemorrhagic Teleangectasia). The same mutation was detected in two
      other members of the family (father and brother of the proband), who showed
      massive polypoid involvement of the stomach at gastroscopy. By taking the family
      history, subtle evidence of Hereditary Teleangectasia was found (nasal bleeding
      and arterovenous malformations) in the three gene carriers. Colonoscopy showed
      polyp occurrence in all three affected members with SMAD4 mutation, with
      prevalence of adenomatous lesions in one (father), of hamartomas in the brother,
      and of a mix of histological types in the proband. The main features of the
      family can be summarized as follows: (A) In hereditary juvenile polyposis,
      lesions of different histology can be detected at colonoscopy; (B) In the gene
      carriers of SMAD4 mutations, lesions of the stomach require careful surveillance
      and, when necessary, surgical interventions; (C) Signs and symptoms of Hereditary
      Hemorrhagic Teleangectasia should be suspected (and searched) in individuals with
      SMAD4 constitutional mutations.

PMID- 30196346
TI  - Falls management framework for supporting an independent lifestyle for older
      adults: a systematic review.
AB  - Falls are one of the common health and well-being issues among the older adults.
      Internet of things (IoT)-based health monitoring systems have been developed over
      the past two decades for improving healthcare services for older adults to
      support an independent lifestyle. This research systematically reviews
      technological applications related to falls detection and falls management. The
      systematic review was conducted in accordance to the preferred reporting items
      for systematic reviews and meta-analysis statement (PRISMA). Twenty-four studies
      out of 806 articles published between 2015 and 2017 were identified and included
      in this review. Selected studies were related to pre-fall and post-fall
      applications using motion sensors (10; 41.67%), environment sensors (10; 41.67%)
      and few studies used the combination of these types of sensors (4; 16.67%). As an
      outcome of this review, we postulated a falls management framework (FMF). FMF
      considered pre- and post-fall strategies to support older adults live
      independently. A part of this approach involved active analysis of sensor data
      with the aim of helping the older adults manage their risk of fall and stay safe
      in their home. FMF aimed to serve the researchers, developers, clinicians and
      policy makers with pre- and post-falls management strategies to enhance the older
      adults' independent living and well-being.

PMID- 30196344
TI  - Characteristics, treatment patterns and outcomes of patients presenting with
      venous thromboembolic events after knee arthroscopy in the RIETE Registry.
AB  - Knee arthroscopy is the most common orthopedic procedure worldwide. While
      incidence of post-arthroscopy venous thromboembolic events (VTE) is low,
      treatment patterns and patient outcomes have not been described. Patients from
      the "Registro Informatizado Enfermedad TromboEmbolica" who had confirmed post
      arthroscopy VTE were compared to patients with provoked, post bone-fracture, and
      to patients with unprovoked VTE. Baseline characteristics, presenting signs and
      symptoms, treatment and outcomes including recurrent VTE, bleeds or death were
      compared. A total of 101 patients with post-arthroscopy VTE and 19,218 patients
      with unprovoked VTE were identified. Post-arthroscopy patients were younger (49.5
      vs. 66 years, P < 0.0001) and had less history of VTE [5.9% vs. 20%, OR 0.26
      (0.11-0.59)]. Among patients with isolated DVT, there were fewer proximal DVT in
      the post-arthroscopy group [40% vs. 86%, OR 0.11 (0.06-0.19)]. Treatment duration
      was shorter in the post-arthroscopy group (174 +/- 140 vs. 311 +/- 340 days, P <
      0.0001) and more often with DOAC [OR 3.67 (1.95-6.89)]. Recurrent VTE occurred in
      6.18 (1.96-14.9) and 11.9 (11.0-12.8) per 100 patient years [HR 0.52 (0.16-1.26)]
      after treatment in the post-arthroscopy and unprovoked groups, respectively.
      Recurrent VTE occurred in 5.17 (1.31-14.1) per 100 patient years in a separate
      post bone-fracture group (n = 147), also not statistically different than the
      post-arthroscopy recurrence rate. After anticoagulation cessation, some patients
      post-knee arthroscopy develop VTE. While our small sample size precludes drawing
      firm conclusions, this signal should warrant further research into the optimal
      treatment duration for these patients, as some patients may be at increased risk
      for long-term recurrence.

PMID- 30196347
TI  - Comparison of the Role of D1- and D2-Like Receptors in the CA1 Region of the
      Hippocampus in the Reinstatement Induced by a Subthreshold Dose of Morphine and
      Forced Swim Stress in Extinguished Morphine-CPP in Rats.
AB  - Reward-seeking and relapse to drug use are two characteristics of addiction and
      reports have indicated the role of hippocampal structures in reward learning. To
      find the best ways of treatment, the understanding of the neurobiological
      mechanisms of reward and its involved factors is a must. For this reason, in the
      present study, we aimed to investigate the role of D1- and D2-like dopamine
      receptors and compared their activities in the CA1 region, focusing on the
      reinstatement induced by forced swim stress (FSS) or the combination of FSS and a
      subthreshold dose of morphine in extinguished morphine-CPP in rats. The rats were
      bilaterally implanted by two separate cannulas into the CA1 region. The animals
      received different doses of SCH23390 or sulpiride (0.5, 2, and 4 ug/0.5 ul
      vehicle/side) into the CA1 region on the reinstatement day and were tested for
      FSS-induced reinstatement or the combination of FSS and a subthreshold dose of
      morphine in separate groups. Our findings indicated that the D1- and D2-like
      receptor antagonists attenuated the reinstatement induced by the combination of
      FSS and the subthreshold dose of morphine. The behavioral results were more
      prominent in the groups of animals that received SCH23390 as compared to
      sulpiride. The data may suggest a role for the dopamine receptors in the CA1
      region in relapse to drugs of abuse, which may be induced by exposure to a
      stressor.

PMID- 30196348
TI  - Effects of an Intraparenchymal Injection of Lidocaine in the Rat Cervical Spinal
      Cord.
AB  - Lidocaine effects in the spinal cord have been extensively investigated over the
      years. Although the intrathecal route is usually used to treat insults occurring
      in the spinal cord, the local delivery drug via intraparenchymal infusions has
      gained increasing favor for the treatment of some neurodegenerative disorders.
      The aim of the present study was to evaluate the behavioral and tissue effects of
      the intraparenchymal injection of different concentrations of lidocaine into the
      rat cervical spinal cord. Young male Sprague-Dawley rats were intraparenchymally
      injected with 0.5%, 1% or 2% lidocaine at the C5 segment of the spinal cord.
      Other rats were injected with saline solution (sham group). Hot plate test was
      determined at 0, 1, 2, 3, 7 and 14 post-injection (pi) days. Rats of each
      experimental group were euthanized either at 1, 2, 3, 7 or 14 pi days. Intact
      animals were used as controls. Sections of the C5 segment were used for
      histological, immunohistochemical or immunofluorescence analysis. Injection of
      0.5% lidocaine did not affect neuronal counting, did not evoke an inflammatory
      reaction, nor induce astrocyte activation. Therefore, a concentration of 0.5%
      lidocaine is suggested to promote anti-inflammatory effects after injury.

PMID- 30196349
TI  - Monitoring of the Cytoskeleton-Dependent Intracellular Trafficking of Fluorescent
      Iron Oxide Nanoparticles by Nanoparticle Pulse-Chase Experiments in C6 Glioma
      Cells.
AB  - Iron oxide nanoparticles (IONPs) are used for various biomedical and therapeutic
      approaches. To investigate the uptake and the intracellular trafficking of IONPs
      in neural cells we have performed nanoparticle pulse-chase experiments to
      visualize the internalization and the fate of fluorescent IONPs in C6 glioma
      cells and astrocyte cultures. Already a short exposure to IONPs for 10 min at 4 
      degrees C (nanoparticle pulse) allowed binding of substantial amounts of
      nanoparticles to the cells, while internalization of IONPs into the cell was
      prevented. The uptake of bound IONPs and the intracellular trafficking was
      started by increasing the temperature to 37  degrees C (chase period). While
      hardly any cellular fluorescence nor any iron staining was detectable directly
      after the nanoparticle pulse, dotted cellular fluorescence and iron patterns
      appeared already within a few minutes after start of the chase incubation and
      became intensified in the perinuclear region during further incubation for up to
      90 min. Longer chase incubations resulted in separation of the fluorescent coat
      from the core of the internalized IONPs. Disruption of actin filaments in C6
      cells strongly impaired the internalization of IONPs, whereas destabilization of
      microtubules traped IONP-containing vesicles to the plasma membrane. In
      conclusion, nanoparticle pulse-chase experiments allowed to synchronize the
      cellular uptake of fluorescent IONPs and to identify for C6 cells an actin
      dependent early and a microtubule-dependent later process in the intracellular
      trafficking of fluorescent IONPs.

PMID- 30196350
TI  - Peramivir: A Review in Uncomplicated Influenza.
AB  - Intravenous peramivir (AlpivabTM; Rapivab(r); Rapiacta(r); PeramiFlu(r)), the
      most recent globally approved inhibitor of influenza neuraminidase, is indicated
      for the treatment of uncomplicated influenza in adults and children from the age
      of 2 years. This article, written from an EU perspective, reviews the clinical
      use of peramivir in this indication and summarizes its pharmacological
      properties. In large, randomized, double-blind, multicentre trials in previously
      healthy adults with uncomplicated influenza, a single infusion of peramivir 600
      mg significantly shortened the median time to resolution of influenza symptoms
      compared with placebo and was noninferior to the recommended oseltamivir regimen
      in terms of this primary outcome. Albeit data are limited, results from a
      noncomparative phase 3 trial in paediatric patients (~ 95% of whom were aged >= 2
      years) with acute uncomplicated influenza receiving the recommended dose of
      peramivir were generally consistent with those in adults. Peramivir was generally
      well tolerated in children and adults participating in these clinical trials,
      with most adverse events of mild to moderate intensity. Given its simple single
      dose regimen and with intravenous administration offering a potential advantage
      over oral administration in individuals with nausea, vomiting or having
      difficulty in swallowing, peramivir provides an additional option for treating
      uncomplicated influenza infection in adults and children from the age of 2 years.

PMID- 30196351
TI  - Ventilator Associated Pneumonia in Children: Current Status and Future Prospects.

PMID- 30196352
TI  - Infective Endocarditis Due to Streptococcus gallolyticus subsp. pasteurianus with
      Pulmonary Vein Obstruction.

PMID- 30196353
TI  - School Refusal Behavior: An Enigma Still To Be Resolved.

PMID- 30196354
TI  - HOXA4-regulated miR-138 suppresses proliferation and gefitinib resistance in non
      small cell lung cancer.
AB  - Many non-small cell lung cancer (NSCLC) patients initially benefiting from
      gefitinib are confronted with acquired resistance. MiR-138 was previously stated
      as a growth inhibitor of several cancer cell lines including NSCLC cells and its
      expression level was significantly lower in gefitinib-resistant cells. The role
      of miR-138 in NSCLC cell lines PC9 and A549 was verified using methyl thiazolyl
      tetrazolium (MTT) assay and colony formation assay. Quantitative real-time PCR
      (RT-PCR) was employed to assess the level of miR-138 in gefitinib-sensitive PC9
      cells and gefitinib-resistant PC9GR cells. Bioinformatic algorithms (TargetScan)
      and rVISTA 2.0 were used to predict binding sites on miR-138 and its target
      genes. MiR-138 inhibited cell proliferation of PC9 and A549 cells. In PC9GR
      cells, miR-138 expression was inhibited. Gefitinib treatment negatively regulated
      miR-138 in PC9 cells. Transfection of PC9GR cells with miR-138 mimics
      significantly reduced cell viability. MiR-138 was directly regulated by Homeobox
      A4 (HOXA4) via an HOXA4-binding site on the promoter region. TargetScan predicted
      numerous miR-138 target genes and EGFR was found to be the functional downstream
      effector of miR-138. We demonstrated that miR-138 is regulated by HOXA4 and
      exerts its functions via inhibiting EGFR expression in NSCLC cells.

PMID- 30196355
TI  - Increasing incidence of candidaemia and shifting epidemiology in favor of Candida
      non-albicans in a 9-year period (2009-2017) in a university Greek hospital.
AB  - PURPOSE: The aim of the present study was to analyze candidaemia's epidemiology
      (incidence, species distribution, and susceptibility rates) and antifungal
      consumption during a 9-year period. METHODS: All candidaemias recorded at The
      University General Hospital of Patras, Greece, between 2009 and 2017 were
      included. Candida isolates were identified using the germ tube test, API 20C AUX
      System, and/or Vitek-2 YST card. Antifungal susceptibility was determined by the
      gradient method according to CLSI. RESULTS: During the study period, 505 episodes
      of candidaemia were observed with an overall incidence of 1.5 episodes per 1000
      hospital admissions (1.1 episodes in 2009 to 1.9 in 2017: P 0.038, r 0.694). C.
      albicans was the leading cause (200 cases; 39.6%), followed by C. parapsilosis
      (185; 36.6%), C. glabrata (56; 11.1%), C. tropicalis (50; 9.9%), C. krusei (8;
      0.2%), C. lusitaniae (5; < 0.1%), and C. guilliermondii (1; < 0.1%). Overall
      resistance to fluconazole, voriconazole, anidulafungin, caspofungin, and
      micafungin (according to CLSI) were 11.6%, 4.1%, 2.0%, 6.0%, and 0.8%,
      respectively. The overall consumption of antifungal drugs was stable, with a
      significant reduction of fluconazole's use in favor of echinocandins.
      CONCLUSIONS: An increase in the incidence of candidaemia and a predominance of
      Candida non-albicans due to decreasing use of fluconazole in favor of more potent
      antifungals, such as echinocandins, are reported in this study.

PMID- 30196356
TI  - Molecular targeting of breast and colon cancer cells by PAR1 mediated apoptosis
      through a novel pro-apoptotic peptide.
AB  - A novel activating peptide was designed and synthesized from V. cholerae
      hemagglutinine protease (HAP) mediated cleavage site of mouse PAR1. The peptide
      "PFISED" interacts with PAR1 in a new site which is different from its thrombin
      mediated conventional activation site and induced a series of new downstream
      signaling pathways. The peptide showed apoptosis in human and mouse breast (MCF-7
      and EAC) and colon (HT29 and CT26) cancer cells where as in the same peptide
      concentration in normal human breast epithelial cells (MCF-10A), normal human
      fibroblast cells (MRC-5), normal mouse peritoneal macrophage cells and normal
      mouse breast and colon tissues did not show any effect. Treatment with this
      peptide enhanced the survival kinetics of EAC induced mice. The peptide mediated
      apoptosis was inhibited in presence of PAR1 inhibitor and was significantly
      reduced in si-PAR1 treated cells that indicate the activating peptide "PFISED"
      induced PAR1 mediated apoptosis of colon and breast cancer cells. This peptide
      induced over expression and activation of PAR1 and its downstream MAP kinase and
      NFkappaB signaling pathways. These signaling pathways enhanced the cellular ROS
      level to kill malignant cells. We report a novel pro-apoptotic peptide which can
      selectively kill malignant cells via its specific target receptor PAR1 which is
      over expressed in the malignant cells and can be used as a molecular target
      therapy for cancer treatment.

PMID- 30196357
TI  - Outcomes After Metabolic Surgery in Asians-a Meta-analysis.
AB  - BACKGROUND: Obesity and type 2 diabetes mellitus (T2DM) are now increasingly
      epidemic in Asia. As obesity and T2DM have different disease patterns in Asians
      compared to Westerners, outcomes after metabolic surgery may differ. The aim of
      this meta-analysis was to gather the current available evidence on the outcomes
      after metabolic surgery in Asians. METHODS: A literature search was conducted in
      September 2017. Four outcome measures were examined: (1) % excess weight loss
      (EWL), (2) post-intervention body mass index (BMI), (3) T2DM resolution or
      improvement, and (4) hypertension resolution. RESULTS: Thirteen publications with
      a total of 1052 patients were analyzed, of which nine were randomized controlled
      trials, and four were case-matched studies. All the studies had a minimum follow
      up duration of at least 1 year. % EWL was significantly higher in those who have
      undergone Roux-en-Y gastric bypass (RYGB) (SMD 0.53, 95% CI 0.12 to 0.94) versus
      sleeve gastrectomy (SG). T2DM resolution/improvement was favorable in those who
      have undergone RYGB (pooled OR 1.39, 95% CI 0.53 to 3.67) versus SG, although not
      statistically significant. Hypertension resolution was not significantly
      different between patients who have undergone SG versus RYGB (pooled OR 0.96, 95%
      CI 0.44 to 2.11). CONCLUSION: RYGB results in better weight loss compared to SG
      in Asians, but the rate of T2DM resolution/improvement and improvement of
      hypertension appears to be similar. In Asian patients without symptoms of gastro
      esophageal reflux disease in whom metabolic surgery is performed mainly for T2DM
      and metabolic syndrome, SG may be the surgery of choice.

PMID- 30196358
TI  - Seroma in breast surgery: all the surgeons fault?
AB  - BACKGROUND: Despite a trend for less radical surgical approaches in breast cancer
      due to better understanding of tumour biology and new treatment options such as
      neoadjuvant chemotherapy (NAC) and intra-operative radiotherapy (IORT), seroma
      production remains one of the main surgical side effects that can result in
      prolonged recovery, delay of radiotherapy and patient discomfort. The aim of this
      study is to provide an update on risk factors for seroma production after breast
      cancer surgery considering the latest treatment options. METHODS: A retrospective
      analysis of seroma production in primary breast cancer patients treated between
      01.01.2010 and 31.12.2014 at the Breast Cancer Centre, University Hospital Ulm,
      was performed. Patients with previous breast/axillary surgery or more than one
      intervention were excluded. Seroma formation was measured using wound drains
      placed in breast and axilla. RESULTS: In total, 581 patients met the inclusion
      criteria. Median age at diagnosis was 60 years, and median BMI 25.6 kg/m2. 60
      (10.3%) patients had a mastectomy, 175 (30.1%) patients received IORT, and 72
      (12.4%) patients received NAC. Median amount of seroma production was 82.5 ml
      (range 0-3012.5 ml). Multivariate analysis revealed that most of the observed
      variation in seroma production was due to type of surgery (mastectomy vs. breast
      conserving), length of surgery and number of removed lymph nodes. Both NAC and
      IORT explained a significant but very small amount of the observed variation in
      seroma production. CONCLUSION: The most important factors for seroma production
      are extent and duration of breast surgery.

PMID- 30196360
TI  - The anatomy of the renal pyelocaliceal system studied by CTU.
AB  - INTRODUCTION AND OBJECTIVES: Knowledge of the pyelocaliceal system anatomy is
      essential for the safe and successful performance of endourologic procedures. The
      purpose of this study was to provide a better understanding of the full three
      dimensional pyelocaliceal system anatomy. METHODS: Morphometric parameters of the
      three-dimensional reconstructions of computed tomography intravenous urography
      scans (n = 25 scans) were analyzed. Both kidneys were divided into three equal
      sized segments (US: upper segment, MS: mid segment, LS: lower segment).
      Infundibular length (IL), infundibular width (IW), the number of calyces, and the
      transverse orientation in hours of a clock of each calyx as well as the dimension
      of the pyelum were determined. RESULTS: The mean upper IL (n = 92) was longer
      than the middle (n = 154) and lower IL (n = 112) (30.6 +/- 7.9 mm vs. 16.4 +/-
      7.7 mm vs. 16.0 +/- 6.0 mm, respectively; P = < 0.0001). IW was significantly
      smaller in the MS [3.7 +/- 1.9 mm], followed by the US [4.6 +/- 1.9 mm], and the
      LS [4.9 +/- 2.2] in the increasing order. No correlation was found between IL and
      IW (Pearson correlation coefficient = 0.1). The US calyces were predominantly
      orientated lateral (8-10 o'clock: 44.5%) and medial (2-4 o'clock: 30.5%), in the
      MS lateral (8-10 o'clock: 87.6%) and anterolateral in the LS (9-12 o'clock:
      67.9%). 74% of the kidneys consisted of 6-8 calyces (mean 7.2 +/- 1.4, range 4
      10), with the majority of the calyces in the MS (3.1 +/- 0.8) followed by the LS
      (2.24 +/- 0.8), and US (1.8 +/- 0.7). There were no statistical differences
      between the right and left kidneys in terms of IL (P = 0.112) and number of
      calyces (P = 0.685). CONCLUSION: Anatomic differences between the three segments
      of the pyelocaliceal system in terms of IL, IW, calyces number, and orientation
      are seen and should be considered when performing an endourologic procedure.

PMID- 30196359
TI  - Predicting attention deficit hyperactivity disorder using pregnancy and birth
      characteristics.
AB  - PURPOSE: The aim of this study was to evaluate maternal, prenatal, perinatal, and
      postpartum parameters as risk factors for the later development of an attention
      deficit hyperactivity disorder (ADHD) in the child. METHODS: Women who had given
      birth at Erlangen University Hospital between 1996 and 1999 were sent a
      questionnaire in 2009. The results of the questionnaire were correlated with the
      prospectively collected data for the births in 1996-1999. RESULTS: A total of 573
      mother and child pairs were analyzed. Forty-four of the mothers reported that
      their child had ADHD (7.7%). No significant associations were found for the
      following parameters: mother's age; mother's educational level; number of the
      pregnancy; maternal weight before and at the end of pregnancy; mother's height;
      alcohol consumption during pregnancy; mode of delivery; gestational week;
      birthweight; umbilical artery blood values; Apgar score at 5 and 10 min; or
      breastfeeding. The parameters of smoking in pregnancy and an Apgar score lower
      than 7 after 1 min were significantly associated with a risk for later
      development of ADHD. CONCLUSIONS: This analysis of maternal, prenatal, perinatal,
      and postnatal parameters found that smoking in pregnancy and a low Apgar score 1
      min after birth are associated with a significantly greater risk for the
      development of ADHD. Beyond the question of the causal mechanism involved, this
      is a relevant finding, since smoking during pregnancy is a preventable risk
      factor.

PMID- 30196361
TI  - Magnetic resonance imaging of the placenta and gravid uterus: a pictorial essay.
AB  - The placenta is commonly overlooked on magnetic resonance imaging of the pregnant
      patient, which is frequently performed for alternative reasons such as to
      characterize fetal or uterine anomalies or to investigate the etiology of acute
      pelvic pain in pregnancy. Placental disorders have potential for significant
      maternal and fetal morbidity and peripartum complications if not recognized and
      treated in a timely manner. The radiologist must be familiar with normal
      placental variants and the spectrum of benign to life-threatening conditions
      affecting the placenta so that the Obstetrician can be promptly notified and
      patient management altered, if necessary. In this pictorial essay, we will
      describe our MR protocol for placental imaging, provide an image-rich review of
      the normal placenta, placental variants, and a variety of pathological conditions
      affecting the placenta and gravid uterus.

PMID- 30196362
TI  - Pearls and pitfalls of response evaluation criteria in solid tumors (RECIST) v1.1
      non-target lesion assessment.
AB  - Oncologic imaging is an important facet of abdominal imaging that radiologists
      encounter nearly every day. Many oncology clinical trials utilize response
      evaluation criteria in solid tumors (RECIST) version 1.1 which divides tumor
      sites into target and non-target lesions. Although RECIST v1.1 provides clear
      instructions regarding the use of imaging in clinical trials, errors in response
      assessment still occur using these criteria. This is especially true of response
      assessment with regards to non-target lesions which involve rules which are less
      well-defined and somewhat subjective. This pictorial essay will review RECIST
      v1.1 guidelines and common non-target lesion errors which can occur at baseline
      and follow-up response assessment.

PMID- 30196363
TI  - Differentiation of hepatic abscess from metastasis on contrast-enhanced dynamic
      computed tomography in patients with a history of extrahepatic malignancy:
      emphasis on dynamic change of arterial rim enhancement.
AB  - OBJECTIVES: The objective of the study is to identify computed tomography (CT)
      findings that differentiate hepatic abscess from hepatic metastasis in a patient
      with a history of extrahepatic malignancy. MATERIALS AND METHODS: This
      retrospective study included 30 patients with 93 hepatic abscesses and 40
      patients with 125 hepatic metastases who had a history of extrahepatic malignancy
      and underwent contrast-enhanced dynamic CT with arterial phase (AP) and portal
      venous phase (PVP). The diagnosis of hepatic abscess and hepatic metastasis was
      made using pathological confirmation or clinical diagnosis. Margin, patchy
      parenchymal enhancement, arterial rim enhancement, dynamic change of arterial rim
      enhancement, size discrepancy of lesions between arterial and portal phases, bile
      duct dilatation, perilesional hyperemia, and perilesional low density were
      evaluated by two radiologists independently. Significant findings for
      differentiating two groups were identified at univariate and multivariate
      analysis with nomogram for predicting hepatic abscess. Interobserver agreement
      was also analyzed for each variable. RESULTS: Multivariate analysis revealed that
      patchy parenchymal enhancement (P < 0.001), arterial rim enhancement persistent
      through PVP (P < 0.001), and perilesional hyperemia (P = 0.013) were independent
      significant findings to predict hepatic abscess than metastasis. Among them,
      arterial rim enhancement persistent through PVP showed a highest odds ratio (OR
      33.73) on multivariate analysis and a highest predictor point on a nomogram for
      predicting hepatic abscess. When two of these three criteria were combined, 80.7%
      (75/93) of hepatic abscess were correctly identified, with a specificity of 85.6%
      (107/125). When all three criteria were satisfied, specificity was up to 100%
      (125/125). CONCLUSIONS: At contrast-enhanced dynamic CT, patchy parenchymal
      enhancement, arterial rim enhancement persistent through PVP, perilesional
      hyperemia, and their combinations may be reliable CT features for differentiating
      hepatic abscess from metastasis in patients with a history of primary
      extrahepatic malignancy.

PMID- 30196364
TI  - MR imaging findings of the prostate gland following prostate artery embolization:
      results from a prospective phase 2 study.
AB  - PURPOSE: To assess changes in imaging and volume characteristics of the prostate
      gland by magnetic resonance (MR) following prostatic artery embolization (PAE)
      for benign prostate hyperplasia. METHODS: With IRB approval, we analyzed
      prospectively acquired MR data of PAE patients at baseline and 6-month following
      treatment from 2015 to 2017. We reviewed prostate MRs looking for sequelae of
      embolization [changes in signal intensity and/or enhancement,
      infection/inflammation, infarction, edema, and change in intravesical prostatic
      protrusion (IPP)]. We calculated the total volume (TV) and central gland volumes
      (CGV) using DynaCAD(r) and measured change in volumes. Analyses were performed
      using SPSS with p < 0.05 considered significant. RESULTS: Forty-three patients (n
      = 43) met our inclusion criteria. 93% (30/43) and 100% (43/43) showed a decrease
      in TV and CGV at 6-months respectively. At baseline, median TV was 86 cc (range
      29.4-232) and median CGV was 54.4 cc (range 12.9-165.5). Median decrease in TV
      was 18.2% (CI 13.3-27.2) (p = 0.0001) and median decrease in CGV was 26.7% (CI
      20.4-35.9) (p = 0.0001). Thirty-seven percent (16/43) of patients had IPP at
      baseline; 100% showed a decrease in size of median lobe at follow-up. At 6-month
      follow-up, 33% (14/43) showed imaging features of infarction, 79% (34/43) had
      decrease in T2-signal intensity, and 51% (22/43) showed a decrease in
      enhancement. None had edema, peri-prostatic fat changes or
      infection/inflammation. CONCLUSION: PAE causes a statistically significant
      reduction in the TV and CGV. There is also a reduction of the degree of IPP. Non
      specific findings of infarction, decrease in T2-signal, and enhancement were also
      seen.

PMID- 30196365
TI  - Contribution of PET imaging to mortality risk stratification in candidates to
      lead extraction for pacemaker or defibrillator infection: a prospective single
      center study.
AB  - PURPOSE: 18F-FDG PET/CT is an emerging technique for diagnosis of cardiac
      implantable electronic devices infection (CIEDI). Despite the improvements in
      transvenous lead extraction (TLE), long-term survival in patients with CIEDI is
      poor. The aim of the present study was to evaluate whether the extension of CIEDI
      at 18F-FDG PET/CT can improve prediction of survival after TLE. METHODS:
      Prospective, monocentric observational study enrolling consecutive candidates to
      TLE for a diagnosis of CIEDI. 18F-FDG PET/CT was performed in all patients prior
      TLE. RESULTS: There were 105 consecutive patients with confirmed CIEDI enrolled.
      An increased 18F-FDG uptake was limited to cardiac implantable electrical device
      (CIED) pocket in 56 patients, 40 patients had a systemic involvement. We had nine
      negative PET in patients undergoing prolonged antimicrobial therapy (22.5 +/-
      14.0 days vs. 8.6 +/- 13.0 days; p = 0.005). Implementation of 18F-FDG PET/CT in
      modified Duke Criteria lead to reclassification of 23.8% of the patients. After a
      mean follow-up of 25.0 +/- 9.0 months, 31 patients died (29.5%). Patients with
      CIED pocket involvement at 18F-FDG PET/CT presented a better survival
      independently of presence/absence of systemic involvement (HR 0.493, 95%CI 0.240
      0.984; p = 0.048). After integration of 18F-FDG PET/CT data, absence of
      overt/hidden pocket involvement in CIEDI and a (glomerular filtration rate) GFR <
      60 ml/min were the only independent predictors of mortality at long term.
      CONCLUSIONS: Patient with CIEDI and a Cold Closed Pocket (i.e., a CIED pocket
      without skin erosion/perforation nor increased capitation at 18F-FDG PET/CT)
      present worse long-term survival. Patient management can benefit by systematic
      adoption of pre-TLE 18F-FDG PET/CT through improved identification of CIED
      related endocarditis (CIEDIE) and hidden involvement of CIED pocket.

PMID- 30196366
TI  - Correction to: Regulation of human brown adipose tissue by adenosine and A2A
      receptors - studies with [15O]H2O and [11C]TMSX PET/CT.
AB  - The original version of this article contained a mistake in the first sentence of
      the Results section of the Abstract.

PMID- 30196367
TI  - Correction to: HIV Persistence on Antiretroviral Therapy and Barriers to a Cure.
AB  - Correction to: Chapter 7 in L. Zhang, S. R. Lewin (eds.), HIV Vaccines and Cure,
      Advances in Experimental Medicine and Biology 1075, https://doi.org/10.1007/978
      981-13-0484-2_7.

PMID- 30196368
TI  - Post-operative cardiovascular complications and time to recurrence in meningioma
      patients treated with versus without pre-operative embolization: a retrospective
      cohort study of 741 patients.
AB  - PURPOSE: Preoperative embolization of radiographically suspected meningiomas is
      often performed to facilitate tumor resection. Its effects on the subsequent
      disease course of meningioma patients have not been studied in detail and
      randomized trials are lacking. The purpose of this study was to explore
      associations of preoperative meningioma embolization with postoperative outcome.
      PATIENTS AND METHODS: Patients undergoing resection of an intracranial meningioma
      at the University Hospital Zurich 2000-2013 (N = 741) were reviewed for the
      inclusion of pre-operative embolization in the management strategy. Annotations
      included demographics, radiographic, surgical, histological and hematological
      parameters, cardiovascular risk factors, pre- and postoperative neurological
      function and gene methylation-based classification. Binary regression and Cox
      proportional hazards models were applied to determine factors associated with
      outcome. RESULTS: Pre-operative embolization was performed in 337 patients (42%).
      Cardiovascular events after surgery comprised mostly deep vein thrombosis (N =
      39) and pulmonary embolisms (N = 64). On multivariate analyses of post-operative
      cardiovascular adverse events controlling for established risk factors, there
      were associations with embolization (OR 2.38, 95% CI 1.37-4.00), and with female
      gender (OR 2.18, 95% CI 1.17-4.08). Recurrence-free survival (RFS) of embolized
      patients was less favorable among patients with WHO grade II or grade III
      meningiomas (median RFS: 4.3 vs. 7.0 years, P = 0.029) or in patients with
      intermediate or malignant gene methylation subtype meningiomas (median RFS: 2.0
      vs. 8.2 years, P = 0.005). CONCLUSION: Pre-operative meningioma embolization may
      cause adverse outcomes. Randomized trials to determine benefit-risk ratios are
      warranted to clarify the role of pre-operative embolization for the treatment of
      meningioma patients.

PMID- 30196369
TI  - Abuse as a risk factor for prenatal depressive symptoms: a meta-analysis.
AB  - Depression is the most common mental disorder in pregnancy. An important risk
      factor in the development of prenatal depression is lifetime history of abuse.
      The current review quantitatively synthesized research on the association between
      history of abuse and prenatal depressive symptoms using a meta-analytic
      technique. A total of 3322 articles were identified through electronic searches
      of the following databases: PsycINFO, PubMed, CINAHL, and EMBASE Cochrane
      Collaboration databases between the years of 1980 and 2016. All were
      independently screened against the following inclusion criteria: articles
      reporting on original data that included measures of prenatal depression and
      abuse. Data were extracted by the first and second authors. Descriptive analyses
      were conducted using Excel version 15.32, and all analyses involving effect sizes
      were conducted using comprehensive meta-analysis (CMA) version 3.0. Seventy
      articles met the inclusion criteria and were included in the meta-analyses. Meta
      bias detected no publication bias. Abuse had a significant positive relation with
      prenatal depressive symptoms, with effect sizes in the moderate range for any
      abuse ([Formula: see text] = 0.287), physical abuse ([Formula: see text] =
      0.271), sexual abuse ([Formula: see text] = 0.259), and emotional abuse
      ([Formula: see text] = 0.340; Cohen 1969. Statistical power analysis for the
      behavioral sciences. Academic Press, New York). The meta-analyses found a robust
      relation between abuse and prenatal depressive symptoms holding across a variety
      of demographic and study design characteristics. These results reinforce the
      established association between trauma victimization and subsequent
      psychopathology, extending current knowledge to specifically address the under
      studied area of prenatal depression. These findings highlight the need for women
      who have survived child or adulthood abuse to receive appropriate referral and
      psychological treatment to mitigate their risk for prenatal depression.

PMID- 30196370
TI  - Dual-phase 16 slice CT angiography in stroke imaging: a poor man's multiphase
      study?
AB  - Multiphase CT angiography (CTA) in collateral assessment provides time-resolved
      cerebral angiograms of the intracranial vasculature, requiring a high-speed
      multidetector CT (MDCT) scanner with >= 64 slices. Unfortunately, many hospitals
      are equipped with lower speed MDCT scanners. Herein, we present our experience
      performing dual-phase CTA (d-CTA) on a 16 slice MDCT with a biphasic rate
      injection to grade intracranial collaterals as predictor of clinical outcome. 42
      patients were evaluated with both dual-phase CTA (d-CTA) and single-phase CTA (s
      CTA) for occluded anterior intracranial circulation and collaterals. They were
      treated with endovascular reperfusion. Univariate and multivariate analyses were
      performed to define the independent predictors for favorable outcome at 3 months.
      Good collateral circulation status on d-CTA was associated with a lower median 24
      h (5 vs. 7.5, p = 0.03) and discharge (2 vs. 4.6, p = 0.04) NIHSS. A logistic
      regression model showed that only age (OR 0.95, 95% CI 0.91-0.98, p = 0.03) and
      good collateral circulation status at d-CTA (OR 4.3, 95% CI 1.87-11.3, p < 0.01)
      were independent predictors of favorable functional outcome at 3 months, but that
      s-CTA was not. The collateral status on d-CTA can be a useful predictor for
      clinical outcome in acute stroke patients. The proposed protocol adapted to a low
      speed MDCT scanner could be of particular interest in hospitals without access to
      the more up-to-date technology.

PMID- 30196371
TI  - Bilateral thalamic and basal ganglia lesions in an old woman: unusual involvement
      of uremic encephalopathy.

PMID- 30196372
TI  - An intoxication mimicking brain death: baclofen.
AB  - Baclofen is a derivative of gamma-aminobutyric acid, used mainly for the
      treatment of muscle spasticity. Baclofen overdose can result in severe
      respiratory depression, autonomic disturbances, seizures and coma. Here we report
      a 15-year-old girl who was found unresponsive, intubated and admitted to the
      PICU. On initial presentation, her Glasgow Coma Score was 3, with fixed dilated
      pupils. EEG revealed cerebral bioelectric activity and ground amplitudes
      significantly lower than normal. Supportive treatments were administered. On the
      2nd PICU day, she regained consciousness and was able to follow commands. She was
      extubated and discharged on hospital day 3. Conclusively emergency physicians
      should consider baclofen overdose in children presenting with acute loss of
      consciousness, flaccidity, and hyporeflexia.

PMID- 30196373
TI  - "Hyperdense artery sign" in early ischemic stroke: diagnostic value of model
      based reconstruction approach in comparison with standard hybrid iterative
      reconstruction algorithm.
AB  - PURPOSE: Hyperdense artery sign is the earliest sign of ischemic stroke on non
      enhanced computed tomography and it can be visible long before parenchymal
      changes. The aim of our study was to compare diagnostic value of model-based
      iterative reconstruction algorithm (IMR) with that of iterative reconstruction
      algorithm (iDose4) in identifying hyperdense artery sign. METHODS: We selected 56
      consecutive patients suspected for ischemic stroke, who underwent a NCCT and that
      demonstrated a vessel occlusion at angio-CT or developed ischemic lesion at
      follow-up CT. Two readers randomly analyzed images of NCCT reconstructed both
      with iDose4 (4 mm) and IMR (2 mm), reporting presence of hyperdense artery sign
      (0: no; 1: yes; 2: not sure). They rated image quality on a 4-point scale (1:
      unacceptable; 4: more than average) and recorded HU values of clot and of normal
      vessel and measured noise index, CNR and SNR. RESULTS: Mean values of CTDI, DLP,
      and ED were respectively of 43 mGy, 819.7 mGy cm, and 1.72 mSv. By analyzing the
      IMR reconstruction, both readers were able to recognize hyperdense vessel sign in
      55/56 patients, while only in 12/56 patients were identified with iDose. IMR
      obtained better rating of image quality (mean score for IMR 3.32 vs 2.53 for
      iDose), higher clot density (57.2 vs 46.7 HU), lower noise index (5 vs 2), higher
      CNR and SNR (respectively 4.2 vs 2 and 16.8 vs 8.5). CONCLUSIONS: Model-based
      approach significantly increases sensitivity in detecting hyperdense artery sign,
      offering higher SNR and CNR in brain CT images in comparison with standard hybrid
      reconstruction algorithm.

PMID- 30196374
TI  - The ammonia-catalyzed release of glycoprotein N-glycans.
AB  - Despite the great significance of release and analysis of glycans from
      glycoproteins, the existing N-glycan release methods are undermined by some
      limitations and deficiencies. The traditional enzymatic protocols feature high N
      glycan release specificity but are generally costly and inefficient for some
      types of N-glycans. The existing chemical methods require harsh reaction
      conditions or are accompanied by the remarkable formation of by-products. Herein,
      we describe a versatile chemical method for the release and analysis of N-glycans
      from glycoproteins. This method differs from the existing methods as only aqueous
      ammonia is used to catalyze the N-glycan release reactions. Optimization of
      reaction conditions was performed using RNase B as a model glycoprotein and the
      obtained results indicated a highest N-glycan yield in ammonia at 60  degrees C
      for 16 h. Comparison of this method with traditional enzymatic protocols and
      recently reported NaClO methods confirmed the good reliability and efficiency of
      the novel approach. We also successfully applied this method to some complex
      biological samples, such as Ginkgo seed protein, fetal bovine serum (FBS) and hen
      egg white, and demonstrated its great compatibility with various neutral N
      glycans, core alpha-1,3-fucosylated N-glycans and sialylated N-glycans. This
      method is very simple and cost-effective, enabling convenient analysis and large
      scale preparation of released reducing N-glycans from various biological samples
      for structural and functional glycomics studies.

PMID- 30196376
TI  - The impact of metabolic syndrome on 30-day outcomes in geriatric hip fracture
      surgeries.
AB  - PURPOSE: Past literature has reported metabolic syndrome (MetS) to complicate
      postoperative care in patients undergoing various surgical procedures. We sought
      to analyze the impact of MetS on 30-day outcomes following hip fracture surgeries
      in the geriatric population. MATERIALS AND METHODS: The 2015-2016 ACS-NSQIP
      database was queried for patients undergoing hip fracture repair using CPT codes
      for total hip arthroplasty (27130), hemiarthroplasty (27125) and open reduction
      internal fixation (27236, 27244, 27245). Only patients >= 65 years of age
      undergoing surgery due to a traumatic hip fracture were included in the study.
      MetS was defined using preset criteria used by other NSQIP studies as the
      presence of-(1) diabetes mellitus AND (2) hypertension requiring medication AND
      (3) BMI >= 30 kg/m2. RESULTS: Out of 31,621 patients, a total of 1388 (4.4%)
      geriatric patients with MetS underwent hip fracture surgery. Following adjusted
      analysis, the presence of MetS was associated with higher odds of a prolonged
      length of stay > 5 days (OR 1.14 [95% CI 1.01-1.29]; p = 0.031), deep SSI (OR
      2.48 [95% CI 1.20-5.14]; p = 0.014), progressive renal insufficiency (OR 3.27
      [95% CI 1.98-5.42]; p < 0.001), acute renal failure (OR 2.08 [95% CI 1.04-4.15];
      p = 0.038), urinary tract infection (OR 1.43 [95% CI 1.12-1.81]; p = 0.004), 30
      day readmissions (OR 1.28 [95% CI 1.08-1.52]; p = 0.005) and a non-home discharge
      (OR 1.42 [95% CI 1.18-1.71]; p < 0.001). CONCLUSION: MetS is associated with a
      significantly increased risk of several postoperative complications, readmissions
      and non-home discharge dispositions. Providers can utilize these data to promote
      the need for better perioperative care in these high-risk patients.

PMID- 30196375
TI  - Contribution of bone turnover markers to the variation in bone mineral density: a
      study in Vietnamese men and women.
AB  - : The present cross-sectional study constructed reference ranges for bone
      resorption marker beta isomerized form of C-terminal crosslinking telopeptides of
      type I collagen (beta-CTX) and bone formation marker procollagen type 1 N
      terminal propeptide (PINP) for the Vietnamese population. We have further shown
      that for a given age and weight, higher levels of beta-CTX were significantly
      associated with bone mineral density in men and women. INTRODUCTION: Normal bone
      is constantly renewed by two opposing processes of resorption and formation which
      can be reflected by bone turnover markers (BTMs). This study sought to define the
      contribution of BTMs to the variation in bone mineral density (BMD) in normal
      individuals. METHODS: The study involved 205 men and 432 women aged between 18
      and 87, who were randomly selected from various districts within Ho Chi Minh
      City, Vietnam. Fasting serum levels of PINP and beta-CTX were determined by
      electrochemiluminescence (Roche, ECLIA). BMD at the lumbar spine (LS) and femoral
      neck (FN) was measured by dual-energy x-ray absorptiometry (Hologic, Waltham, MA,
      USA). RESULTS: Among those aged < 50 years, women had lower PINP and beta-CTX
      levels than men, but among those aged > 50 years, women had higher PINP and beta
      CTX levels than men. In the multiple linear regression analysis, beta-CTX-but not
      PINP-was significantly associated with both femoral neck (P = 0.008) and lumbar
      spine BMD (P = 0.008) and the association was independent of gender, age, and
      body weight. The proportion of variance in BMD attributable to beta-CTX was 1%
      for femoral neck BMD and 2% for lumbar spine BMD. CONCLUSION: The elevation in
      bone formation marker PINP and bone resorption marker beta-CTX in postmenopausal
      women was greater than in elderly men. However, only beta-CTX was modestly but
      significantly associated with BMD.

PMID- 30196377
TI  - The Effects of Neurokinin-1 Receptor Antagonist in an Experimental Autoimmune
      Cystitis Model Resembling Bladder Pain Syndrome/Interstitial Cystitis.
AB  - To identify the effects of the neurokinin-1 receptor (NK1R) antagonist aprepitant
      in treating pelvic pain, micturition symptoms, and bladder inflammation in mice
      with experimental autoimmune cystitis (EAC) similar to bladder pain
      syndrome/interstitial cystitis (BPS/IC). Female C57BL/6 mice were divided into
      the following three groups: normal control, EAC, and EAC plus aprepitant. EAC was
      induced in mice by duplicate immunization with bladder homogenate. In the EAC
      model group, EAC mice were given PBS by gavage once a day during the fourth week.
      In the EAC plus aprepitant group, aprepitant was administered instead of PBS in
      the same way. After 4 weeks, pelvic pain threshold and urination habits of mice
      were analyzed, as well as the bladder weight to body weight ratio, and histologic
      assessment of the expression of IL-1beta, TNF-alpha, intercellular adhesion
      molecule 1 (ICAM-1), and NK1R in bladder tissue. EAC mice mimicked the phenotype
      and pathophysiologic lesions of BPS/IC well. Compared to PBS-treated EAC mice,
      the mice treated with aprepitant exhibited higher pain threshold values, less
      number of total urine spots or small urine spots, lower bladder weight to body
      weight ratio, and reduced bladder inflammation with less mast cell infiltration
      and decreased expressions of IL-1beta, TNF-alpha, and ICAM-1 in bladder tissue.
      There was no difference in NK1R expression in bladders treated with or without
      aprepitant. The NK1R antagonist aprepitant relieved pelvic pain, urinary
      symptoms, and bladder inflammation in EAC mice. This indicated that NK1R may be a
      novel therapeutic target in BPS/IC treatment.

PMID- 30196378
TI  - Volume-based parameters on FDG PET may predict the proliferative potential of
      soft-tissue sarcomas.
AB  - INTRODUCTION: Soft-tissue sarcomas (STS) are rare types of tumors that have
      variable levels of tumor differentiation. F-18 fluorodeoxyglucose positron
      emission tomography (FDG PET) has been established as an useful tool for STS
      patients, and the metabolic tumor volume (MTV) and total lesion glycolysis (TLG)
      are reported to be useful in various cancers. We compared the diagnostic value of
      four PET parameters (maximum standardized uptake value [SUVmax], SUVmean, MTV,
      and TLG) from two acquisition timings for predicting the expression of the
      pathological marker of cell proliferation Ki-67, based on pathological
      investigation. MATERIALS AND METHODS: In this retrospective study, we
      investigated 20 patients (59 +/- 19 years old, 18-87 years old) with
      pathologically confirmed STS who underwent FDG PET before surgical intervention.
      The patients fasted >= 6 h before the intravenous injection of FDG. The whole
      body was scanned twice; at an early phase (61.5 +/- 2.6 min) and at a delayed
      phase (118.0 +/- 2.1 min) post-injection. The SUVmax, SUVmean, MTV, and TLG of
      the primary lesion were measured with a tumor boundary determined by SUV >= 2.0.
      Ki-67 was measured using MIB-1 immunohistochemistry. We used Pearson's
      correlation coefficient to analyze the relationships between the PET parameters
      and Ki-67 expressions. The Kaplan-Meier analysis with the log-rank test was
      performed to compare overall survival between high-group and low-group at each of
      the four PET parameters and Ki-67 expression. RESULTS: All four PET parameters at
      each phase showed significant correlations with Ki-67. Among them, the Pearson's
      correlation coefficient (r) was largest for TLG (r = 0.76 and 0.77 at the early
      and delayed phases, respectively), followed by MTV (0.70 and 0.72), SUVmax (r =
      0.65 and 0.66), and SUVmean (r = 0.62 and r = 0.64). From early to delayed
      phases, the SUVmax and SUVmean both increased in all 20 patients, whereas the MTV
      and TLG increased in 13/20 (65%) and 16/20 (80%) patients, respectively. None of
      the %increases of the PET parameters were significantly correlated with Ki-67.
      The overall survival was shorter for high-SUVmax, high-SUVmean, high-TLG, and
      high-Ki-67 groups than the other groups, although the difference did not reach
      statistical significance. CONCLUSION: The SUVmax, SUVmean, MTV, and TLG acquired
      at both 1 and 2 h after injection showed significant correlations with Ki-67.
      Among them, correlation coefficient with Ki-67 expression was highest for TLG,
      although the best parameter should be determined in a larger population. The
      delayed-phase FDG PET was equally useful as that of early-phase to predict tumor
      aggressiveness in STS.

PMID- 30196379
TI  - Relationship Between Pulmonary-to-Systemic-Blood-Flow Ratio (Qp:Qs) Based on
      Cardiac Catheterization and Indices Derived from Simultaneously Measured End
      Tidal CO2 (EtCO2) in Children with Complex Congenital Heart Disease.
AB  - CO2 removal by the lungs depends upon ventilation and pulmonary blood flow, with
      end tidal CO2 (EtCO2) as surrogate for it. We studied indices based on EtCO2
      measured routinely during anesthesia for cardiac catheterization, along with
      simultaneously calculated Qp:Qs (pulmonary-to-systemic-blood-flow ratio) in
      children with complex congenital heart disease to assess the relationship between
      these measures. A retrospective, single-center, correlational cohort study was
      conducted at a tertiary-care, free-standing children's hospital. All included
      subjects had Qp:Qs calculated as well as EtCO2 and PaCO2 documented during a
      single cardiac catheterization. Children with stage-1 single ventricle or complex
      biventricular repair with highly variable Qp:Qs were defined as Group 1, and
      Group 2 comprised those with stage 2 or 3 repairs with less variable Qp:Qs.
      Exclusion criteria were uncuffed artificial airway, EtCO2 > PaCO2, and abnormally
      high Qp:Qs. EtCO2 indices were defined as EtCO2:PaCO2 (alveolar functional
      fraction) and EtCO2 gap (PaCO2-EtCO2). Correlation coefficients were obtained
      between Qp:Qs and EtCO2 indices in both groups. A total of 29 patients in Group 1
      and 24 in Group 2 underwent final analysis. Even with highly variable Qp:Qs,
      Group 1 showed a strong correlation between Qp:Qs and EtCO2:PaCO2 (r = 0.83, p <
      0.0001). A similarly strong correlation was maintained in Group 2 (r = 0.79, p <
      0.0001) and in both groups combined (r = 0.86, p < 0.0001). A very strong
      negative correlation was present between Qp:Qs and EtCO2 gap (r = - 0.77, p <
      0.0001). EtCO2:PaCO2 has a very strong correlation with Qp:Qs simultaneously
      calculated during catheterization. It can be an additional parameter to estimate
      Qp:Qs in critical management of children with congenital heart disease. Our
      results also provide a basis for future prospective studies to assess dynamic
      changes in EtCO2-based indices and Qp:Qs.

PMID- 30196380
TI  - Examining the Utility of Coronary Artery Lack of Tapering and Perivascular
      Brightness in Incomplete Kawasaki Disease.
AB  - BACKGROUND: In 2017, the AHA published revised guidelines for the diagnosis of
      Kawasaki disease (KD). In the absence of compelling data supporting or refuting
      the utility of lack of tapering (LT) and perivascular brightness (PB), expert
      panel consensus removed LT and PB from consideration. We hypothesize that LT and
      PB are unreliable, subjective findings, non-specific to KD, which can be seen in
      systemic febrile illnesses without KD and in normal controls. METHODS: We
      performed a single-center retrospective study from 1/2008 to 12/2016. De
      identified coronary artery (CA) echocardiographic clips from patients 0-10 years
      old were interpreted blindly by six pediatric cardiologists. Subjects were
      grouped as follows: (1) healthy: afebrile with benign murmur, (2) KD: IVIG
      treatment, 4-5 clinical criteria at presentation, (3) incomplete KD (iKD): IVIG,
      1-3 clinical criteria, (4) Febrile: >=3 days of fever, no IVIG, KD not suspected.
      The presence or absence of LT and PB was recorded. Inter-rater and intra-rater
      reliabilities were analyzed using intra-class correlation coefficient, Fleiss'
      Kappa and Cohen's Kappa coefficients. RESULTS: We interpreted 117 echocardiograms
      from healthy (27), KD (30), iKD (32), and febrile (28) subjects. Analysis showed
      moderate agreement in CA z score measurements. LT and PB were observed by most
      readers in control groups. LT exhibited fair inter-reader agreement (reliability
      coefficient 0.36) and PB slight inter-reader agreement (reliability coefficient
      0.13). Intra-rater reliability was inconsistent for both parameters. CONCLUSIONS:
      LT and PB are subjective, poorly reproducible features that can be seen in
      febrile patients without KD and in healthy children.

PMID- 30196382
TI  - Risk factors for early B cell recovery following single-dose rituximab therapy in
      Japanese children with steroid-dependent nephrotic syndrome.

PMID- 30196381
TI  - Is Sutureless Technique Beneficial in the Primary Repair of Total Anomalous
      Pulmonary Venous Connection? A Systematic Review and Meta-Analysis.
AB  - A meta-analysis was performed for a comparison of outcomes between sutureless
      technique and conventional surgery for primary repair for total anomalous
      pulmonary venous connection (TAPVC). Electronic databases including PubMed,
      EMbase, Scopus, and Cochrane Library were searched systematically for the single
      arm studies regarding sutureless repair or conventional surgery, and two-arm
      studies compared the outcomes of sutureless repair and conventional surgery for
      TAPVC. Corresponding data were extracted and the methodological quality was
      assessed by two reviewers independently. 26 studies were included, involving a
      total of 2702 patients. It was observed that compared with conventional surgery,
      sutureless technique was associated with a lower occurrence rate of post
      operative pulmonary veins obstruction (PVO) (4.6% vs. 13.5%, OR 0.54 in favor of
      sutureless technique) and re-operations due to PVO (3.4% vs. 12.4%, 0.25 in favor
      of sutureless technique). However, meta-analyses of post-operative early (OR
      0.57; 95% CI 0.27-1.19; P = 0.13), late (OR 0.37; 95% CI 0.13-1.06; P = 0.13),
      and overall (OR 0.61; 95% CI 0.36-1.03; P = 0.07) mortality showed no significant
      difference between sutureless technique and conventional surgery. Compared with
      conventional surgery, sutureless technique was associated with a lower occurrence
      rate of post-operative PVO and re-operations due to PVO. Meanwhile, post
      operative early, late, and overall mortality were not statistically different
      between two surgical approaches. Sutureless technique is beneficial in the
      primary repair of TAPVC regarding post-operative PVO and re-operations due to
      PVO. However, the level of evidence was low and randomized controlled trials
      should be designed to evaluate the safety and effectiveness of sutureless
      technique for TAPVC.

PMID- 30196383
TI  - A clinical predictive model of chronic kidney disease in children with posterior
      urethral valves.
AB  - BACKGROUND: Posterior urethral valves (PUVs) are associated with severe
      consequences to the urinary tract and are a common cause of chronic kidney
      disease (CKD). The aim of this study was to develop clinical predictive model of
      CKD in a cohort of patients with PUVs. METHODS: In this retrospective cohort
      study, 173 patients with PUVs were systematically followed up at a single
      tertiary unit. The primary endpoint was CKD >= stage 3. Survival analyses were
      performed by Cox regression proportional hazard models with time-fixed and time
      dependent covariables. RESULTS: Mean follow-up time was 83 months (SD, 70
      months). Sixty-five children (37.6%) developed CKD stage >= 3. After adjustment
      by the time-dependent Cox model, baseline creatinine, nadir creatinine,
      hypertension, and proteinuria remained as predictors of the endpoint. After
      adjustment by time-fixed model, three variables were predictors of CKD >= stage
      3: baseline creatinine, nadir creatinine, and proteinuria. The prognostic risk
      score was divided into three categories: low-risk (69 children, 39.9%), medium
      risk (45, 26%), and high-risk (59, 34.1%). The probability of CKD >= stage 3 at
      10 years age was estimated as 6%, 40%, and 70% for patients assigned to the low
      risk, medium-risk, and high-risk groups, respectively (P < 0.001). The main
      limitation was the preclusion of some relevant variables, especially bladder
      dysfunction, that might contribute to a more accurate prediction of renal
      outcome. CONCLUSION: The model accurately predicts the risk of CKD in PUVs
      patients. This model could be clinically useful in applying timely intervention
      and in preventing the impairment of renal function.

PMID- 30196384
TI  - Heterogeneous distribution of trastuzumab in HER2-positive xenografts and
      metastases: role of the tumor microenvironment.
AB  - Most HER2-positive metastatic breast cancer patients continue to relapse.
      Incomplete access to all target HER2-positive cells in metastases and tumor
      tissues is a potential mechanism of resistance to trastuzumab. The location of
      locally bound trastuzumab was evaluated in HER2-positive tissues in vivo and as
      in vivo xenografts or metastases models in mice. Microenvironmental elements of
      tumors were related to bound trastuzumab using immunohistochemical staining and
      include tight junctions, vasculature, vascular maturity, vessel patency, hypoxia
      and HER2 to look for correlations. Trastuzumab was evaluated alone and in
      combination with bevacizumab. Dynamic contrast-enhanced magnetic resonance
      imaging parameters of overall vascular function, perfusion and apparent
      permeability were compared with matched histological images of trastuzumab
      distribution and vascular patency. Trastuzumab distribution is highly
      heterogeneous in all models examined, including avascular micrometastases of the
      brain and lung. Trastuzumab distributes well through the extravascular
      compartment even in conditions of high HER2 expression and poor convective flow
      in vivo. Microregional patterns of trastuzumab distribution in vivo do not
      consistently correlate with vascular density, patency, function or maturity;
      areas of poor trastuzumab access are not necessarily those with poor vascular
      supply. The number of vessels with perivascular trastuzumab increases with time
      and higher doses and dramatically decreases when pre-treated with bevacizumab.
      Areas of HER2-positive tissue without bound trastuzumab persist in all
      conditions. These data directly demonstrate tissue- and vessel-level barriers to
      trastuzumab distribution in vivo that can effectively limit access of the drug to
      target cells in brain metastases and elsewhere.

PMID- 30196385
TI  - Platelet-rich plasma and the shoulder: clinical indications and outcomes.
AB  - PURPOSE OF REVIEW: The orthopedic community has seen a rapid rise in the clinical
      use of platelet-rich plasma (PRP) in the management of shoulder pathologies over
      the past decade. The purpose of this paper is to review the current literature
      regarding the indications and outcomes of PRP for the surgical and non-surgical
      management of common shoulder pathologies, including rotator cuff tears. RECENT
      FINDINGS: Multiple studies have been published recently regarding the use of PRP
      for the operative and non-operative treatment of rotator cuff tears. There has
      been less research published on the use of PRP in the management of other
      conditions of the shoulder. Despite attempts to standardize and classify PRP
      formulations, there remains great variation in the inter- and intra-subjection
      composition, preparation, and administration techniques of PRP, limiting the
      conclusions that can be drawn regarding the utility and effectiveness of this
      biologic treatment as reported by Mazzocca et al. (J Bone Joint Surg Am.
      94(4):308-16, 2012). Recent literature has shown equivocal to minor benefit of
      PRP use for shoulder pain, function, and healing. While few complications have
      been reported and PRP administration appears to carry little risk to the patient,
      the body of literature is currently inconclusive regarding the clinical benefit
      and cost-effectiveness of PRP in the treatment of shoulder pathology. As for PRP
      use specifically as an adjunct to surgical rotator cuff repairs, there is no
      clear consensus on its effectiveness in either clinical or structural outcomes.
      To further delineate the efficacy of PRP for shoulder pathology, it is essential
      that more double-blinded, randomized controlled investigations with large sample
      sizes and standardized PRP preparations be performed.

PMID- 30196386
TI  - Management of Midfoot Fractures and Dislocations.
AB  - PURPOSE OF REVIEW: To outline the classic and recent literature of midfoot
      fractures and dislocations. RECENT FINDINGS: There has been an evolution of
      implant technology to include mini-fragment fixation, suture fixation, and
      staples. Their efficacy is still being elucidated in the literature. Also, there
      has been a recent push for primary fusion, which we will discuss. Open reduction
      internal fixation of the midfoot remains to be the gold standard treatment, to
      which all other treatments are compared. It remains to be seen if adjunct
      fixation techniques are efficacious enough to provide a good result. Further
      study is needed to determine which patients are likely to progress to
      debilitating arthrosis and require fusion.

PMID- 30196387
TI  - Third nerve decompression by anterior petroclinoid ligament opening after
      clipping of posterior communicating artery aneurysm-How I do it.
AB  - BACKGROUND: Posterior communicating artery aneurysms sometimes present with
      partial or complete oculomotor nerve palsy, due to direct oculomotor nerve
      compression, irritation by subarachnoid blood, or both. Superiority of surgical
      clipping over endovascular coiling in terms of postoperative outcome is still
      controversial. METHOD: Direct oculomotor nerve decompression by opening of the
      anterior petroclinoid ligament during aneurysm clipping is performed as a simple
      and feasible surgical maneuver which allows to improve the decompression effect
      obtained by aneurysm exclusion. CONCLUSION: Anterior petroclinoid ligament
      opening permits to achieve a better oculomotor nerve decompression. Its
      efficiency on the recovery of the deficit needs to be proved by larger series.

PMID- 30196388
TI  - Correction to: Behavioral Genetics and Attributions of Moral Responsibility.
AB  - The original version of this article unfortunately contained a few mistakes in
      the Introduction section.

PMID- 30196391
TI  - Case report of cardiac herniation after sleeve pneumonectomy with superior vena
      cava reconstruction.
AB  - Cardiac herniation is a complication that occurs after intrapericardial
      pneumonectomy. It is life-threatening unless promptly diagnosed and surgery
      performed. We report a case of cardiac herniation after right intrapericardial
      pneumonectomy following radiotherapy for lung cancer. The patient developed
      cardiac herniation with sudden hypotension following a switch to the spine
      position. An immediate switch to the lateral decubitus position improved the
      cardiocirculatory dynamics, and surgical patch closure was performed. The
      circulation dynamics was unstable for several hours after surgery with elevated
      enzyme levels, which improved 2 days later. Immediate thoracotomy before
      irreversible myocardial damage resulted in a successful outcome. The risk of
      cardiac herniation should always be considered after intrapericardial
      pneumonectomy.

PMID- 30196389
TI  - Towards Three-Dimensional Dynamic Regulation and In Situ Characterization of
      Single Stem Cell Phenotype Using Microfluidics.
AB  - Mesenchymal stem cells and pluripotent stem cells are recognized as promising
      tools for tissue engineering, cell therapy, and drug screening. Their use in
      therapy requires the production of a sufficient number of cells committed to
      functional regenerative phenotypes. Time- and magnitude-controlled application of
      mechanical and biochemical cues is required to appropriately control the
      evolution of stem cell phenotype in 3D. The temporal monitoring of the impact of
      these cues on the diverse fates of individual stem cells is also needed to ensure
      the reliability of the differentiation processes. However, macro-scale
      bioreactors are limited in regulating stem environment and display limited
      capability to monitor heterogeneities at the single cell level. In turn,
      microfluidics devices are emerging as powerful tools for tightly controlling
      culture parameters and precisely monitoring stem cell behavior. This work
      summarizes recent advances in the applications of microfluidics for the dynamic
      regulation and characterization of stem cells in 3D.

PMID- 30196390
TI  - 3-Aminobenzamide Prevents Concanavalin A-Induced Acute Hepatitis by an Anti
      inflammatory and Anti-oxidative Mechanism.
AB  - BACKGROUND AND AIMS: Concanavalin A is known to activate T cells and to cause
      liver injury and hepatitis, mediated in part by secretion of TNFalpha from
      macrophages. Poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors have been shown to
      prevent tissue damage in various animal models of inflammation. The objectives of
      this study were to evaluate the efficacy and mechanism of the PARP-1 inhibitor 3
      aminobenzamide (3-AB) in preventing concanavalin A-induced liver damage. METHODS:
      We tested the in vivo effects of 3-AB on concanavalin A-treated mice, its effects
      on lipopolysaccharide (LPS)-stimulated macrophages in culture, and its ability to
      act as a scavenger in in vitro assays. RESULTS: 3-AB markedly reduced
      inflammation, oxidative stress, and liver tissue damage in concanavalin A-treated
      mice. In LPS-stimulated RAW264.7 macrophages, 3-AB inhibited NFkappaB
      transcriptional activity and subsequent expression of TNFalpha and iNOS and
      blocked NO production. In vitro, 3-AB acted as a hydrogen peroxide scavenger. The
      ROS scavenger N-acetylcysteine (NAC) and the ROS formation inhibitor
      diphenyleneiodonium (DPI) also inhibited TNFalpha expression in stimulated
      macrophages, but unlike 3-AB, NAC and DPI were unable to abolish NFkappaB
      activity. PARP-1 knockout failed to affect NFkappaB and TNFalpha suppression by 3
      AB in stimulated macrophages. CONCLUSIONS: Our results suggest that 3-AB has a
      therapeutic effect on concanavalin A-induced liver injury by inhibiting
      expression of the key pro-inflammatory cytokine TNFalpha, via PARP-1-independent
      NFkappaB suppression and via an NFkappaB-independent anti-oxidative mechanism.

PMID- 30196392
TI  - The Wilbrand's knee does not exist in the optic chiasm.

PMID- 30196393
TI  - Delayed-onset paralysis induced by spontaneous spinal epidural hematoma
      communicated with hematoma in the paraspinal muscle in a 6-month-old girl: a case
      report.
AB  - Spontaneous spinal epidural hematoma (SSEH) very rarely develops in infants
      younger than 1 year old. To our knowledge, no previous case of delayed-onset
      paralysis induced by SSEH communicated with hematoma in the paraspinal muscle has
      been reported in the literature. The authors present the case of a 6-month-old
      girl with a tumor mass on her back who developed a paresis of her bilateral lower
      limbs. On spinal magnetic resonance imaging, the epidural mass appeared to be a
      dumbbell type and communicated with the mass in the paraspinal muscle through
      T12/L1 intervertebral foramen at the right side. After excision of the mass in
      the paraspinal muscle, hemi-laminectomy of T10-L3 was performed. No solid lesion
      was also present in the spinal canal and it was found to be an epidural hematoma.
      No malignancy was observed on pathological examination, and vascular and nerve
      system tumors were negative. When a tumor mass suddenly develops on the back of
      an infant and motor impairment of the lower limbs develops as the mass gradually
      enlarges, differential diagnosis should be performed taking SSEH into
      consideration.

PMID- 30196394
TI  - Suppressing Tau Aggregation and Toxicity by an Anti-Aggregant Tau Fragment.
AB  - Tau aggregation is a hallmark of a group of neurodegenerative diseases termed
      Tauopathies. Reduction of aggregation-prone Tau has emerged as a promising
      therapeutic approach. Here, we show that an anti-aggregant Tau fragment
      (F3DeltaKPP, residues 258-360) harboring the DeltaK280 mutation and two proline
      substitutions (I277P & I308P) in the repeat domain can inhibit aggregation of Tau
      constructs in vitro, in cultured cells and in vivo in a Caenorhabditis elegans
      model of Tau aggregation. The Tau fragment reduced Tau-dependent cytotoxicity in
      a N2a cell model, suppressed the Tau-mediated neuronal dysfunction and
      ameliorated the defective locomotion in C. elegans. In vitro the fragment
      competes with full-length Tau for polyanionic aggregation inducers and thus
      inhibits Tau aggregation. Our combined in vitro and in vivo results suggest that
      the anti-aggregant Tau fragment may potentially be used to address the
      consequences of Tau aggregation in Tauopathies.

PMID- 30196395
TI  - Transcriptomic Analysis Reveals Sex-Dependent Expression Patterns in the
      Basolateral Amygdala of Dominant and Subordinate Animals After Acute Social
      Conflict.
AB  - The basolateral amygdala (BLA) is a critical nucleus mediating behavioral
      responses after exposure to acute social conflict. Male and female Syrian
      hamsters both readily establish a stable dominant-subordinate relationship among
      same-sex conspecifics, and the goal of the current study was to determine
      potential underlying genetic mechanisms in the BLA facilitating the establishment
      of social hierarchy. We sequenced the BLA transcriptomes of dominant,
      subordinate, and socially neutral males and females, and using de novo assembly
      techniques and gene network analyses, we compared these transcriptomes across
      social status within each sex. Our results revealed 499 transcripts that were
      differentially expressed in the BLA across both males and females and 138
      distinct gene networks. Surprisingly, we found that there was virtually no
      overlap in the transcript changes or in gene network patterns in males and
      females of the same social status. These results suggest that, although males and
      females reliably engage in similar social behaviors to establish social
      dominance, the molecular mechanisms in the BLA by which these statuses are
      obtained and maintained are distinct.

PMID- 30196396
TI  - Hyaluronic acid (HA)-based hydrogels for full-thickness wound repairing and skin
      regeneration.
AB  - In this work, two kinds of hyaluronic acid (HA)-based hydrogels were fabricated:
      one is made from physical freezing-thawing of HA solution (HA1), and the other is
      from chemical cross-linking of HA and polysaccharide (HA2). They were applied to
      repair full-thickness skin defects with New Zealand rabbits as the test animals,
      using powder HA and cotton dress as the references. The wound starts to heal
      after wounds were disinfected with iodine followed by coating with HA2, HA1, HA
      and cotton dress (the control), respectively. They were recorded as 4 treatments
      (groups), HA2, HA1, HA and the control. The healing progress was followed and
      tested in the duration of 56 days, and the biological repairing mechanism was
      explored. From the wound area alteration, white blood cell (WBC) measurements and
      H&E staining, HA2 was the most promising treatment in promoting the wound healing
      with least serious scar formation. Immunochemistry analyses and real-time PCR
      tests of the bio-factors involved in the wound healing, vascular endothelial
      growth factor (VEGF), alpha-smooth muscle actin (alpha-SMA) and transforming
      growth factor beta-1 (TGF-beta1), exhibited that HA2 enhanced VEGF and alpha-SMA
      secretion but reduced TGF-beta1 expression at early stage, which alleviated the
      wound inflammation, improved the skin regeneration and relieved the scar
      formation.

PMID- 30196398
TI  - An Update on the Therapeutic Potential of Stem Cells.
AB  - The seeming setbacks noted for stem cells underscore the need for experimental
      studies for safe and efficacious application to patients. Both clinical and
      experimental researchers have gained valuable knowledge on the characteristics of
      stem cells, and their behavior in different microenvironment. This introductory
      chapter focuses on adult mesenchymal stem cells (MSCs) based on the predominance
      in the clinic. MSCs can be influenced by inflammatory mediators to exert immune
      suppressive properties, commonly referred to as "licensing." Interestingly, while
      there are questions if other stem cells can be delivered across allogeneic
      barrier, there is no question on the ability of MSCs to provide this benefit.
      This property has been a great advantage since MSCs could be available for
      immediate application as "off-the-shelf" stem cells for several disorders, tissue
      repair and gene/drug delivery. Despite the benefit of MSCs, it is imperative that
      research continues with the various types of stem cells. The method needed to
      isolate these cells is outlined in this book. In parallel, safety studies are
      needed; particularly links to oncogenic event. In summary, this introductory
      chapter discusses several potential areas that need to be addressed for safe and
      efficient delivery of stem cells, and argue for the incorporation of
      microenvironmental factors in the studies. The method described in this chapter
      could be extrapolated to the field of chimeric antigen receptor T-cells (CAR-T).
      This will require application to stem cell hierarchy of memory T-cells.

PMID- 30196397
TI  - Reduction in social anxiety after MDMA-assisted psychotherapy with autistic
      adults: a randomized, double-blind, placebo-controlled pilot study.
AB  - RATIONALE: Standard therapeutic approaches to reduce social anxiety in autistic
      adults have limited effectiveness. Since 3,4-methylenedioxymethamphetamine (MDMA)
      assisted psychotherapy shows promise as a treatment for other anxiety disorders,
      a blinded, placebo-controlled pilot study was conducted. OBJECTIVES: To explore
      feasibility and safety of MDMA-assisted psychotherapy for reduction of social
      fear and avoidance that are common in the autistic population. METHODS: Autistic
      adults with marked to very severe social anxiety were randomized to receive MDMA
      (75 to 125 mg, n = 8) or inactive placebo (0 mg, n = 4) during two 8-h
      psychotherapy sessions (experimental sessions) in a controlled clinical setting.
      Double-blinded experimental sessions were spaced approximately 1 month apart with
      3 non-drug psychotherapy sessions following each. The primary outcome was change
      in Leibowitz Social Anxiety Scale (LSAS) Total scores from Baseline to one month
      after the second experimental session. Outcomes were measured again six months
      after the last experimental session. RESULTS: Improvement in LSAS scores from
      baseline to the primary endpoint was significantly greater for MDMA group
      compared to the placebo group (P = 0.037), and placebo-subtracted Cohen's d
      effect size was very large (d = 1.4, CI - 0.074, 2.874). Change in LSAS scores
      from baseline to 6-month follow-up showed similar positive results (P = 0.036),
      with a Cohen's d effect size of 1.1 (CI - 0.307, 2.527). Social anxiety remained
      the same or continued to improve slightly for most participants in the MDMA group
      after completing the active treatment phase. CONCLUSIONS: This pilot trial
      demonstrated rapid and durable improvement in social anxiety symptoms in autistic
      adults following MDMA-assisted psychotherapy. Initial safety and efficacy
      outcomes support expansion of research into larger samples to further investigate
      this novel treatment for social anxiety. TRIAL REGISTRATION: clinicaltrials.gov
      identifier, NCT02008396.

PMID- 30196399
TI  - Single-Step Plasmid Based Reprogramming of Human Dermal Fibroblasts to Induced
      Neural Stem Cells.
AB  - Reprogramming of somatic cells to induced pluripotent stem cells (iPSC) and
      subsequent differentiation opened up the opportunity of deriving cell types in
      vitro which (like neurons) had a very restricted accessibility in the past.
      However, cell culture protocols for iPSC reprogramming, neural induction and
      differentiation tend to be labor and time intensive, costly and commonly depend
      on viral vector delivery. Single-step reprogramming to induced neural stem cells
      (iNSC) avoids many of the necessary intermediate steps of the aforementioned
      method but yields a cell type that proliferates over longer time spans and
      readily differentiates to mature neurons when required. Here we describe a
      plasmid based reprogramming protocol employing defined, commercially available
      components for induction and proliferation of iNSC, followed by a defined, small
      molecule based differentiation step toward mature neurons. The described method
      might be of particular interest for groups with limited resources and/or
      restricted access to higher biosafety level facilities required for viral
      transduction, but also for groups requiring a high throughput for dealing with
      large numbers of cell lines.

PMID- 30196400
TI  - Isolation and Analysis of Mesenchymal Progenitors of the Adult Hematopoietic
      Niche.
AB  - Mesenchymal stromal cells are an important component of the adult hematopoietic
      stem cell niche. They are a diverse population of cells that include a hierarchy
      of primitive, intermediate, and mature osteoprogenitors that support HSCs and
      supply the bone with matrix producing osteoblast. To understand the different
      roles played by individual types of progenitors, it is necessary to separate
      individual populations and analyze them in a controlled environment. Here we
      describe two transplantation models, an ectopic bone forming assay and an
      intravenous injection assay, in which niche components can be isolated and
      manipulated to dissect their individual properties.

PMID- 30196401
TI  - Identification and Isolation of Mice and Human Hematopoietic Stem Cells.
AB  - Hematopoietic stem cells (HSCs) are multipotent cells capable of differentiating
      into all types of blood cells. The important feature of the HSCs is their ability
      to repopulate the complete blood cells after BM ablation. For clinical
      application, cord blood derived HSCs and G-CSF mobilized peripheral blood HSCs
      are good alternative to bone marrow HSCs. For immunological and hematological
      studies the obvious choice of model organism is Mouse. Therefore, understanding
      HSCs in murine model is important. In this chapter, we describe the
      common/currently used methods to isolate and identify human and mouse HSCs.

PMID- 30196402
TI  - Identification and Characterization of Hair Follicle Stem Cells.
AB  - Hair follicle stem cells (HFSCs) are epithelial cells that inhabit in the bulge
      region of hair follicles. They govern development of hair follicle as well as
      periodically regeneration of hair follicle. Under special condition, they also
      play roles in homeostasis of skin and other skin appendages. To characterize
      HFSCs in vitro, HFSCs must be isolated and cultured. In this chapter, we
      introduce a mechanical method to isolate HFSCs from mouse vibrissa hair follicle,
      and a modified method to culture isolated HFSCs. We also describe methods to
      characterize HFSCs, including clone formation assay and chamber graft assay.

PMID- 30196403
TI  - Methods of Mesenchymal Stem Cell Homing to the Blood-Brain Barrier.
AB  - Mesenchymal stem/stromal cells (MSC) are multipotent cells that can be isolated
      from adult and fetal tissues. In vitro, MSCs show functional plasticity by
      differentiating into specialized cells of all germ layers. MSCs are of relevant
      to medicine and have been proposed for several disorders. MSCs can be
      transplanted across allogeneic barriers as "off the shelf" cells. This chapter
      focuses on methods to deliver MSCs to the brain because neurological pathology
      such as damage due to stroke can lead to debilitating mental and physical
      problems. In general, neurological diseases are difficult to treat, partly due to
      the challenge in getting drugs across the blood-brain barrier (BBB). MSCs as well
      as other stem cells can cross the BBB. The described method begins to develop
      procedures, leading to efficient delivery of drugs to the brain. Here describe
      how MSCs can be propagated from bone marrow aspirates and their utility in
      delivering small RNA to the brain. The chapter discusses the issue to enhance
      efficient delivery of MSCs to the brain.

PMID- 30196404
TI  - 3D Bioprinting and Stem Cells.
AB  - Three-dimensional (3D) in vitro modeling is increasingly relevant as two
      dimensional (2D) cultures have been recognized with limits to recapitulate the
      complex endogenous conditions in the body. Additionally, fabrication technology
      is more accessible than ever. Bioprinting, in particular, is an additive
      manufacturing technique that expands the capabilities of in vitro studies by
      precisely depositing cells embedded within a 3D biomaterial scaffold that acts as
      temporary extracellular matrix (ECM). More importantly, bioprinting has vast
      potential for customization. This allows users to manipulate parameters such as
      scaffold design, biomaterial selection, and cell types, to create specialized
      biomimetic 3D systems.The development of a 3D system is important to recapitulate
      the bone marrow (BM) microenvironment since this particular organ cannot be
      mimicked with other methods such as organoids. The 3D system can be used to study
      the interactions between native BM cells and metastatic breast cancer cells
      (BCCs). Although not perfect, such a system can recapitulate the BM
      microenvironment. Mesenchymal stem cells (MSCs), a key population within the BM,
      are known to communicate with BCCs invading the BM and to aid in their transition
      into dormancy. Dormant BCCs are cycling quiescent and resistant to chemotherapy,
      which allows them to survive in the BM to resurge even after decades. These
      persisting BCCs have been identified as the stem cell subset. These BCCs exhibit
      self-renewal and can be induced to differentiate. More importantly, this BCC
      subset can initiate tumor formation, exert chemoresistance, and form gap junction
      with endogenous BM stroma, including MSCs. The bioprinted model detailed in this
      chapter creates a MSC-BC stem cell coculture system to study intercellular
      interactions in a model that is more representative of the endogenous 3D
      microenvironment than conventional 2D cultures. The method can reliably seed
      primary BM MSCs and BC stem cells within a bioprinted scaffold fabricated from
      CELLINK Bioink. Since bioprinting is a highly customizable technique, parameters
      described in this method (i.e., cell-cell ratio, scaffold dimensions) can easily
      be altered to serve other applications, including studies on hematopoietic
      regulation.

PMID- 30196405
TI  - Characterization of Gastrospheres Using 3D Coculture System.
AB  - To understand the molecular mechanisms involved in gastric disorders and
      regeneration, we need an in vitro tridimensional (3D) culture model, which can
      mimic the in vivo gastric microenvironment. A 3D coculture system named
      gastrosphere is proposed herein, composed of primary human gastric epithelial and
      stromal cells. The primary cultures were obtained from endoscopic gastric
      biopsies, and after mechanical and enzymatic dispersion, epithelial (HGE3) and
      stromal (HGS12) cells were expanded. After extensive immunocytochemical
      characterization, cells were seeded onto 96-well round bottom plates previously
      covered with 1% agarose. Cells were cultured in KM-F12 culture medium with 10%
      fetal bovine serum (FBS), antibiotics, and antimycotics, in humidified air at 37 
      degrees C and atmosphere containing 5% CO2 for 72 h or until spheres formation.
      Then gastrospheres were carefully transferred to a rotary cell culture system
      (RCCS-4), and maintained for 07, 14, 21, and 28 days. Gastrospheres were
      morphologically characterized by immunocytochemistry [cytokeratins (CK),
      vimentin, alpha-smooth muscle actin (alpha-SMA), laminin (LN), fibronectin (FN),
      and type IV collagen (CIV), proliferating cell nuclear antigen (PCNA)], and
      electron microscopy. In gastrospheres, the cytokeratin-positive epithelial cells
      were found in the outer layer, while vimentin-positive stromal cells were
      localized in the center of the gastrospheres. PCNA+ cells were mainly seen at the
      peripheral and in the intermediary region while nestin+ cells were also depicted
      in the latter zone. Scanning electron microscopy revealed groups of cohesive
      gastric cells at the periphery, while transmission electron microscopy
      demonstrated some differentiated mucous-like or zymogenic-like cells in the
      periphery and stromal structures located at the center of the 3D structures.
      Extracellular matrix was deposed between cells. Our data suggest that in vitro
      gastrospheres recapitulate the in vivo gastric microenvironment.

PMID- 30196406
TI  - Markers and Methods to Study Adult Midgut Stem Cells.
AB  - Stem cells have emerged as a promising cell source to heal, replace or regenerate
      tissue and organs damaged by aging, injury or diseases. The intestinal epithelium
      is the most rapidly renewing tissue in our body, which is maintained by
      intestinal stem cells (ISCs), located at the bottom of the crypts. ISCs
      continuously replace lost or injured intestinal epithelial cells in organisms
      ranging from Drosophila to humans. The adult Drosophila midgut provides an
      excellent in vivo model system to study ISC behavior during stress, regeneration,
      aging and infection. There are several signaling pathways/genes have been
      identified to regulate ISCs self-renewal and differentiation during normal and
      pathological conditions. A significant number of genetic tools and markers have
      been developed in the last one decade to study Drosophila ISCs behavior. Here, we
      describe some of the markers and methods used to study ISCs behavior in adult
      midgut of Drosophila.

PMID- 30196407
TI  - Quantitative Analysis of Intestinal Stem Cell Dynamics Using Microfabricated Cell
      Culture Arrays.
AB  - Regeneration of intestinal epithelium is fueled by a heterogeneous population of
      rapidly proliferating stem cells (ISCs) found in the base of the small intestine
      and colonic crypts. ISCs populations can be enriched by fluorescence-activated
      cell sorting (FACS) based on expression of combinatorial cell surface markers,
      and fluorescent transgenes. Conventional ISC culture is performed by embedding
      single ISCs or whole crypt units in a matrix and culturing in conditions that
      stimulate or repress key pathways to recapitulate ISC niche signaling. Cultured
      ISCs form organoid, which are spherical, epithelial monolayers that are self
      renewing, self-patterning, and demonstrate the full complement of intestinal
      epithelial cell lineages. However, this conventional "bulk" approach to studying
      ISC biology is often semiquantitative, low throughput, and masks clonal effects
      and ISC phenotypic heterogeneity. Our group has recently reported the
      construction, long-term biocompatibility, and use of microfabricated cell raft
      arrays (CRA) for high-throughput analysis of single ISCs and organoids. CRAs are
      composed of thousands of indexed and independently retrievable microwells, which
      in combination with time-lapse microscopy and/or gene-expression analyses are a
      powerful tool for studying clonal ISC dynamics and micro-niches. In this
      protocol, we describe how CRAs are used as an adaptable experimental platform to
      study the effect of exogenous factors on clonal stem cell behavior.

PMID- 30196408
TI  - Detection, Labeling, and Culture of Lung Stem and Progenitor Cells.
AB  - Identification, isolation, and clonal culture of stem cells is essential for
      understanding their proliferative and differentiation potential, and the cellular
      and molecular mechanisms that regulate their fate. Akin to development in vivo,
      the in vitro growth of adult lung epithelial stem cells requires support of
      mesenchymal-derived growth factors. In the adult mouse lung, epithelial
      stem/progenitor cells are defined by the phenotype CD45neg CD31neg EpCAMpos
      CD104pos CD24low, and mesenchymal cells are defined by the phenotype CD45neg
      CD31neg EpCAMneg Sca-1hi. Here we describe a method for primary cell isolation
      from the adult mouse lung, a flow cytometry strategy for fractionation of
      epithelial stem/progenitor cells and mesenchymal cells, and a three-dimensional
      epithelial colony-forming assay.

PMID- 30196409
TI  - Isolation, Characterization and Differentiation of Mouse Cardiac Progenitor
      Cells.
AB  - Despite several strategies developed for replenishing the dead myocardium after
      myocardial infarction (MI), stem cell therapy remains the leading method to
      regenerate new myocardium. Although induced pluripotent stem cells (iPS) and
      transdifferentiation of the differentiated cells have been used as novel
      approaches for myocardial regeneration, these approaches did not yield very
      successful results for myocardial regeneration in in vivo studies. Asynchronous
      contractility of newly formed cardiomyocytes with the existing cardiomyocytes is
      the most important issue with iPS approach, while very low yield of
      transdifferentiated cardiomyocytes and their less chances to beat in the same
      rhythm as existing cardiomyocytes in the MI heart are important caveats with
      transdifferentiation approach. CSCs are present in the heart and they have the
      potential to differentiate into myocardial cells. However, the number of resident
      CSCs is very low. Therefore, it is important to get maximum yield of CSCs during
      isolation process from the heart. Increasing the number of CSCs and initiating
      their differentiation ex vivo are crucial for CSC-based stem cell therapy. Here,
      we present a better method for isolation, characterization and differentiation of
      CSCs from the mouse heart. We also demonstrated morphological changes in the CSCs
      after 2 days, 3 days, and 7 days in maintenance medium and a separate group of
      CSCs cultured for 12 days in differentiation medium using Phase-Contrast
      microscopy. We have used different markers for identification of CSCs isolated
      from the mouse heart such as marker for mouse CSC, Sca-1, cardiac-specific
      markers NKX2-5, MEF2C, GATA4, and stemness markers OCT4 and SOX2. To characterize
      the differentiated CSCs, we used CSCs maintained in differentiation medium for 12
      days. To evaluate differentiation of CSCs, we determined the expression of
      cardiomyocyte-specific markers actinin and troponin I. Overall; we described an
      elegant method for isolation, identification, differentiation and
      characterization of CSCs from the mouse heart.

PMID- 30196410
TI  - Isolating and Characterizing Adipose-Derived Stem Cells.
AB  - The research and application of regeneration medicine will require a reliable
      source of stem cells. Adipose tissue has proven to be an easily accessible and
      rich source of adult stem cells, termed adipose-derived stem cells (ASCs). ASCs
      have the most important advantage over stem cells from other available sources.
      There is no other human tissue as abundant as adipose tissue, making it possible
      to isolate adequate numbers of ASCs for potential clinical applications. Here, we
      describe detailed methods for isolating and characterizing ASCs. These procedures
      can be applied to adipose tissue not only for humans but also for other species.

PMID- 30196411
TI  - Enzyme-Free Isolation of Adipose-Derived Mesenchymal Stem Cells.
AB  - Mesenchymal stem cells (MSCs) are a population of multipotent cells that can be
      isolated from various adult and fetal tissues, including adipose tissue. These
      cells contain enormous clinical and basic research appeal due to their plasticity
      to differentiate into cells of all germ layers in vitro, cross allogeneic
      barriers in vivo, and suppress inflammation. Methods to isolate adipose-derived
      MSCs (ADSCs) primarily rely on enzymatic digestion of the adipose tissue using
      harsh enzymes such as collagenase. However, these harsh enzymes are expensive and
      can have detrimental effects on the ADSCs, including risks of using xenograft
      components in clinical application. This chapter focuses on methods of isolating
      ADSCs from adipose tissue without enzymatic digestion.

PMID- 30196412
TI  - Identification and Characterizations of Annulus Fibrosus-Derived Stem Cells.
AB  - Annulus fibrosus (AF) injuries are common in degenerative disc disease (DDD) and
      can lead to substantial deterioration of the intervertebral disc. However, repair
      or regeneration of AF remains challenging. Recently, we have found that there
      exists a subpopulation of cells, which form colonies in vitro and could self
      renew, in AF tissue. These cells express typical surface antigen molecules of
      mesenchymal stem cells, including CD29, CD44, and CD166. They also express common
      stem cell markers such as Oct-4, nucleostemin, and SSEA-4. In addition, they can
      be induced to differentiate into adipocytes, osteocytes, and chondrocytes. Being
      AF tissue-specific, such AF-derived stem cells may potentially be an ideal
      candidate for DDD treatments using stem cell-based cell therapies or tissue
      engineering approaches.

PMID- 30196413
TI  - Maintenance of Tendon Stem/Progenitor Cells in Culture.
AB  - Tendon stem/progenitor cells (TSCs) are tendon-specific adult stem cells, which
      play crucial roles in tendon homeostasis, repair or regeneration once tendons are
      injured. Additionally, their pathological role in the development of tendinopathy
      in response to excessive mechanical loading placed on the tendon is also
      implicated. Similar to other adult stem cells, TSCs also exhibit universal
      characteristics of stem cells including colony formation in culture, self-renewal
      and multidifferentiation potential. Nevertheless, once TSCs are isolated from
      tendinous tissues and cultured in vitro, they may quickly lose stemness by
      undergoing differentiation. To maintain and prolong the stemness of TSCs in
      culture, we have developed two effective methods, namely culturing TSCs in
      hypoxic condition, or in growth media supplemented with low levels of PGE2. Here
      we present these methods in detail, along with the detailed description of the
      procedures to isolate TSCs from tendon samples and to culture them in vitro.

PMID- 30196414
TI  - Intravital Imaging to Understand Spatiotemporal Regulation of Osteogenesis and
      Angiogenesis in Cranial Defect Repair and Regeneration.
AB  - Angiogenesis plays a critical role in skeletal repair and regeneration. Our
      understanding of the intricate relationship between osteogenesis and angiogenesis
      at a repair site has been hindered by the lack of an effective approach that
      allows tracking of bone healing and neovascularization simultaneously at a high
      spatiotemporal resolution in living animals. To overcome this barrier, we have
      recently established a cranial bone defect window chamber model in mice that
      enables high-resolution, four-dimensional imaging analyses of bone defect healing
      using multiphoton laser scanning microscopy (MPLSM). The windowed defect model
      confers imaging of the defect through both micro computed tomography (microCT)
      and MPLSM in vivo, facilitating lineage tracing and longitudinal analyses of
      osteogenesis and angiogenesis in repair. The windowed chamber model further
      permits insertion of cellular implants or bone graft materials, aiding in
      spatiotemporal analyses of the interactions between biomaterials and vascular
      microenvironment in living animals. In this chapter, we describe the improved
      technique for establishing the chronic cranial defect window chamber model for
      long-term imaging as well as the imaging analysis protocols for quantitative
      analyses of osteogenesis and angiogenesis at the site of bone defect repair.

PMID- 30196415
TI  - Beating Heart Cells from Hair-Follicle-Associated Pluripotent (HAP) Stem Cells.
AB  - The neural stem-cell marker nestin is expressed in hair follicle stem cells
      located in the bulge area which are termed hair-follicle-associated pluripotent
      (HAP) stem cells. HAP stem cells can differentiate into neurons, glia,
      keratinocytes, smooth muscle cells, and melanocytes in vitro. Subsequently, we
      demonstrated that HAP stem cells could affect nerve and spinal cord regeneration
      in mouse models. We subsequently demonstrated that HAP stem cells differentiated
      into beating cardiac muscle cells. The differentiation potential to cardiac
      muscle is greatest in the upper part of the mouse whisker follicle. The beat rate
      of the cardiac muscle cells differentiated from HAP stem cells was stimulated by
      isoproterenol and inhibited by propanolol. The addition of activin A, bone
      morphogenetic protein 4, and basic fibroblast growth factor, along with
      isoproternal, induced the cardiac muscle cells to form tissue sheets of beating
      heart muscle cells. Under hypoxic conditions, HAP stem cells differentiated into
      troponin-positive cardiac-muscle cells at a higher rate that under normoxic
      conditions. Hypoxia did not influence the differentiation to other cell types.
      This method is appropriate for future use with human hair follicles to produce
      hHAP stem cells in sufficient quantities for future heart, nerve, and spinal cord
      regeneration in the clinic.

PMID- 30196416
TI  - Generation of FLIP and FLIP-FlpE Targeting Vectors for Biallelic Conditional and
      Reversible Gene Knockouts in Mouse and Human Cells.
AB  - Rapid generation of conditional knockout models in a diploid system is
      challenging. Recently, CRISPR-FLIP strategy has been introduced, which
      facilitates the generation of biallelic conditional or reversible gene knockouts
      in various mammalian cell lines including mouse and human pluripotent stem cells
      by codelivery of the CRISPR/Cas9 system and a universal intronic cassette-FLIP
      and FLIP-FlpE. Here, I describe the design and cloning method of FLIP and FLIP
      FlpE targeting vectors for conditional and reversible gene knockouts. This method
      is applicable to mouse embryonic stem cells, human induced pluripotent stem
      cells, and adult stem cell-derived organoids.

PMID- 30196417
TI  - Analytical Platforms and Techniques to Study Stem Cell Metabolism.
AB  - Over the past decade, advances in systems biology or 'omics techniques have
      enabled unprecedented insights into the biological processes that occur in cells,
      tissues, and on the organism level. One of these technologies is the
      metabolomics, which examines the whole content of the metabolites in a given
      sample. In a biological system, a stem cell for instance, there are thousands of
      single components, such as genes, RNA, proteins, and metabolites. These multiple
      molecular species interact with each other and these interactions may change over
      the life-time of a cell or in response to specific stimuli, adding to the
      complexity of the system. Using metabolomics, we can obtain an instantaneous
      snapshot of the biological status of a cell, tissue, or organism and gain
      insights on the pattern(s) of numerous analytes, both known and unknown, that
      result because of a given biological condition. Here, we outline the main methods
      to study the metabolism of stem cells, including a relatively recent technology
      of mass spectrometry imaging. Given the abundant and increasing interest in stem
      cell metabolism in both physiological and pathological conditions, we hope that
      this chapter will provide incentives for more research in these areas to
      ultimately reach wide network of applications in biomedical, pharmaceutical, and
      nutritional research and clinical medicine.

PMID- 30196418
TI  - The prevalence of chronic low back pain and lumbar deformities in patients with
      Parkinson's disease: implications on spinal surgery.
AB  - PURPOSE: This observational study was aimed at quantification of low back pain
      (LBP) in Parkinsonian patients and its morphological correlation. BACKGROUND:
      Parkinson's disease (PD) is a common disabling condition in the elderly
      population. Parkinsonian patients frequently are troubled by LBP. Causes for LBP
      in PD are muscular imbalances by the movement disorder itself and skeletal
      degeneration. METHODS: Ninety-seven PD patients and 97 controls were inquired
      about low back pain through the Oswestry Low Back Pain Disability Questionnaire
      and visual analogue scales. Fifty-four patients with LBP underwent X-ray of the
      lumbar spine in two planes and flexion-extension views. Parkinson's disease was
      characterized by stage, disease duration, motor score, lateralization of symptoms
      and dosage of medication. RESULTS: LBP occurred significantly more frequent in PD
      (87.6%) compared to controls (62.6%) with longer duration and higher pain
      intensity. Pain intensity and disability scores were associated with higher PD
      stages and higher motor scores. Patients with the hypokinetic PD subtype
      experienced more pain intensity. X-ray of the lumbar spine revealed lumbar
      arthrosis in 79.6%, scoliosis in 38.8% and spondylolisthesis in 24.1% of PD
      patients with LBP. Lateralization of scoliosis and PD symptoms were significantly
      correlated. Only a small portion of PD patients with LBP received specialized
      orthopaedic treatment. CONCLUSION: LBP and lumbar degeneration are common in PD.
      Both are related to movement disorder symptoms. The knowledge about
      musculoskeletal conditions in Parkinson's disease is important for an
      interdisciplinary conservative or operative treatment decision of LBP. These
      slides can be retrieved under Electronic Supplementary Material.

PMID- 30196419
TI  - Correction to: Total disc replacement versus fusion for lumbar degenerative disc
      disease: a systematic review of overlapping meta-analyses.
AB  - The authors declare that when writing their article [1] they referenced two
      previously published papers [2, 3]. Several sentences on pages 807, 808, and 813
      were similar to sentences from these two previously published articles.

PMID- 30196420
TI  - Validation of the Croatian version of the Oswestry Disability Index.
AB  - PURPOSE: To translate, cross-culturally adapt, and validate the Croatian version
      of the Oswestry Disability Index (ODI). METHODS: The original English-language
      ODI was cross-culturally adapted into Croatian and then evaluated in a group of
      114 patients with chronic low back pain (LBP) at the Department of Neurosurgery,
      Zagreb University School of Medicine. Confirmatory factor analysis (CFA) was
      conducted with three models: two were theory driven (unidimensional and two
      dimensional-static and dynamic factors); the other was based on our exploratory
      factor analysis (EFA). Internal consistency and test-retest reliability were
      evaluated using Cronbach's alpha and the intraclass correlation coefficient
      (ICC), respectively. Construct validity was assessed by evaluating the
      correlation between the ODI and Visual Analogue Scale (VAS), and between the ODI
      and 36-item short form survey (SF-36) scores. RESULTS: The EFA-derived two
      dimensional structure explained 82.7% of the total variance and was significantly
      better than the other models (P < 0.001); however, none of the models had
      acceptable fit. Internal consistency (Cronbach alpha = 0.84) and test-retest
      reliability (ICC = 0.94) were satisfactory. The ODI was positively correlated
      with VAS (rs = 0.54, P < 0.001) and negatively correlated with all of the SF-36
      sections (rs = - 0.35 to - 0.64, P < 0.001, all), apart from the role-physical
      (rs = - 0.02, P = 0.767). CONCLUSIONS: The Croatian version of the ODI has
      acceptable psychometric properties. It appears to be suitable for assessment of
      LBP and treatment outcomes in Croatian-speaking patients. Overall, there was no
      evidence to reject the original unidimensional structure in favor of a two-factor
      solution. As such, the unidimensional structure should continue to be used in
      future studies. These slides can be retrieved under Electronic Supplementary
      Material.

PMID- 30196421
TI  - Characterization and mapping of secondary metabolites of Streptomyces sp. from
      caatinga by desorption electrospray ionization mass spectrometry (DESI-MS).
AB  - The discovery of new secondary metabolites is a challenge to biotechnologists due
      to the emergence of superbugs and drug resistance. Knowledge about biodiversity
      and the discovery of new microorganisms have become major objectives; thus, new
      habitats like extreme ecosystems have become places of interest to research. In
      this context, caatinga is an unexplored biome. The ecosystem caatinga is a rich
      habitat for thermophilic microbes. Its high temperature and dry climate cause
      selective microbes to flourish and become established. Actinobacteria (Caat 1-54
      genus Streptomyces sp.) isolated from the soil of caatinga was investigated to
      characterize and map its secondary metabolites by desorption electrospray
      ionization mass spectrometry imaging (DESI-MSI). With this technique, the
      production of bioactive metabolites was detected and associated with the
      different morphological differentiation stages within a typical Streptomyces sp.
      life cycle. High-resolution mass spectrometry, tandem mass spectrometry, UV-Vis
      profiling and NMR analysis were also performed to characterize the metabolite
      ions detected by DESI-MS. A novel compound, which is presumed to be an analogue
      of the antifungal agent lienomycin, along with the antimicrobial compound
      lysolipin I were identified in this study to be produced by the bacterium. The
      potency of these bioactive compounds was further studied by disc diffusion assays
      and their minimum inhibitory concentrations (MIC) against Bacillus and
      Penicillium were determined. These bioactive metabolites could be useful to the
      pharmaceutical industry as candidate compounds, especially given growing concern
      about increasing resistance to available drugs with the emergence of superbugs.
      Consequently, the unexplored habitat caatinga affords new possibilities for novel
      bioactive compound discovery. Graphical Abstract ?.

PMID- 30196422
TI  - Magnetic carbon nanocomposites as a MALDI co-matrix enhancing MS-based glycomics.
AB  - More than 50% of all known proteins are glycosylated, which is critical for many
      biological processes such as protein folding and signal transduction.
      Glycosylation has proven to be associated with different mammalian diseases such
      as breast and liver cancers. Therefore, characterization of glycans is highly
      important to facilitate a better understanding of the development and progression
      of many human diseases. Although matrix-assisted laser desorption ionization-mass
      spectrometry (MALDI-MS) offers several advantages such as ease of operation and
      short analysis times, however, due to the complexity of glycan structures and
      their low ionization efficiency, there are still challenges that need to be
      addressed to achieve sensitive glycan analysis. Here, magnetic carbon
      nanocomposites (CNPs@Fe3O4 NCs) were used as a new MALDI matrix or co-matrix for
      the analysis of glycans derived from different model glycoproteins and human
      blood serum samples. The addition of CNPs@Fe3O4 NCs to the matrix significantly
      enhanced glycan signal intensity by several orders of magnitude, and effectively
      controlled/reduced/eliminated in-source decay (ISD) fragmentation. The latter was
      attained by modulating CNPs@Fe3O4 NCs concentrations and allowed the simultaneous
      study of intact and fragmented glycans, and pseudo-MS3 analysis. Moreover,
      CNPs@Fe3O4 NCs was also effectively employed to desalt samples directly on MALDI
      plate, thus enabling direct MALDI-MS analysis of unpurified permethylated glycans
      derived from both model glycoproteins and biological samples. On-plate desalting
      enhanced sensitivity by reducing sample loss. Graphical abstract ?.

PMID- 30196423
TI  - The genetic landscape of gliomas arising after therapeutic radiation.
AB  - Radiotherapy improves survival for common childhood cancers such as
      medulloblastoma, leukemia, and germ cell tumors. Unfortunately, long-term
      survivors suffer sequelae that can include secondary neoplasia. Gliomas are
      common secondary neoplasms after cranial or craniospinal radiation, most often
      manifesting as high-grade astrocytomas with poor clinical outcomes. Here, we
      performed genetic profiling on a cohort of 12 gliomas arising after therapeutic
      radiation to determine their molecular pathogenesis and assess for differences in
      genomic signature compared to their spontaneous counterparts. We identified a
      high frequency of TP53 mutations, CDK4 amplification or CDKN2A homozygous
      deletion, and amplifications or rearrangements involving receptor tyrosine kinase
      and Ras-Raf-MAP kinase pathway genes including PDGFRA, MET, BRAF, and RRAS2.
      Notably, all tumors lacked alterations in IDH1, IDH2, H3F3A, HIST1H3B, HIST1H3C,
      TERT (including promoter region), and PTEN, which genetically define the major
      subtypes of diffuse gliomas in children and adults. All gliomas in this cohort
      had very low somatic mutation burden (less than three somatic single nucleotide
      variants or small indels per Mb). The ten high-grade gliomas demonstrated
      markedly aneuploid genomes, with significantly increased quantity of
      intrachromosomal copy number breakpoints and focal amplifications/homozygous
      deletions compared to spontaneous high-grade gliomas, likely as a result of DNA
      double-strand breaks induced by gamma radiation. Together, these findings
      demonstrate a distinct molecular pathogenesis of secondary gliomas arising after
      radiation therapy and identify a genomic signature that may aid in
      differentiating these tumors from their spontaneous counterparts.

PMID- 30196424
TI  - Familial Cancer Clustering in Patients with Prolactinoma.
AB  - People are at higher risk for malignancy as they get older or have a strong
      family history of cancer. This study aims to collect family history of cancer in
      a large cohort of patients with pituitary adenomas (PA) in outpatient clinic from
      years 2005-2017. Overall, 46.6% of 1062 patients with PA had a family member
      affected with cancer. Breast cancer in family members was reported in 15.3% of
      patients with prolactinomas which was significantly higher than in families of
      patients with non-functioning pituitary adenomas (NFPA) (10.0%) or acromegaly
      (6.8%) (p = 0.004). Lung cancer in family members was reported in 12.1% of
      patients with prolactinomas, significantly higher than in families of NFPA
      patients (7.0%, p = 0.049). Colorectal cancer in relatives of patients with PA
      was reported with any type of PA. Furthermore, patients with a positive family
      history of malignancy were diagnosed with PA at an earlier age than patients with
      a negative family history (43.6 +/- 15.9 vs 46.0 +/- 16.4 years, p = 0.015).
      Female patients with prolactinoma are more commonly diagnosed before the age of
      25 years. Forty-two percent of patients with PA diagnosed before the age of 25
      years had a second- and third-degree relative with cancer, significantly higher
      than patients with PA diagnosed later in life (25.8%, p < 0.001). Breast, lung,
      and colon cancers in second- and third-degree relatives were reported in
      significantly higher proportion of patients with PA diagnosed before the age of
      25 years, compared with patients with PA diagnosed later in life (breast cancer:
      10.9 vs 6.1%, p = 0.033; lung cancer: 10.9 vs 5.8%, p = 0.02; colon cancer: 9.5
      vs 4.0%, p = 0.004). These results suggest familial cancer clustering in patients
      with prolactinoma and young patients with PA (younger than 25 years at diagnosis
      of PA). In particular, there is a strong association between prolactinoma and
      family history of breast and lung cancers. Further research of possible shared
      genetic susceptibility of prolactinoma and breast and lung cancers is needed.

PMID- 30196425
TI  - Tumor grade and progesterone receptor status predict 21-gene recurrence score in
      early stage invasive breast carcinoma.
AB  - PURPOSE: The 21-gene recurrence score (RS) assay is increasingly utilized to
      predict the risk of recurrence in early stage estrogen receptor (ER)-positive
      breast cancer. We hypothesize that tumor grade and progesterone receptor (PR)
      status predict RS categorization. METHODS: We identified women between the ages
      of 18 and 74 years with stage I or II, ER-positive, invasive carcinoma of the
      breast from the Surveillance Epidemiology End-Results database from 2010 to 2013.
      Multivariable logistic regression was performed to determine factors associated
      with high-risk RS. RESULTS: We identified 42,530 patients that met inclusion
      criteria. Multivariable logistic regression demonstrated that grade I tumors [OR
      (odds ratio) 0.33, 95% CI (confidence interval) 0.31-0.37] and PR positive (PR+)
      status (OR 0.16, 95% CI 0.15-0.17) were significantly less likely to be
      associated with high-risk RS. Of patients with grade I PR+ tumors, 1% was in the
      high-risk group by the traditional cutoffs and 4% was in the high-risk group by
      the TAILORx cutoffs. The percentage of patients with high-risk RS remained low
      for grade I PR+ tumors regardless of age, race, tumor size, and lymph node
      status. CONCLUSIONS: We found that grade I PR+ tumors are associated a < 5%
      probability of having high-risk RS regardless of other patient demographic or
      pathologic factors. This suggests that the histologic factors of grade and PR
      status should be taken into consideration before ordering the 21-gene recurrence
      score assay.

PMID- 30196426
TI  - Parent experience in the resuscitation room: how do they feel?
AB  - The aim of this study is to describe the experience of parents present in the
      resuscitation room during the attention given to their children in the pediatric
      emergency department, and to identify areas for improvement in this regard. This
      was a prospective study carried out in a third-level pediatric hospital. Children
      with life-threatening pathologies are treated in the resuscitation room of the
      pediatric emergency department. A survey was carried out among parents present in
      the resuscitation room during the period September 2016-August 2017. Excluded
      were the parents of children that died and those with a language barrier. The
      parents were interviewed in person or over the phone within 72 h of the care
      provided in the resuscitation room. Fifty surveys were completed (15 in person
      and 35 by phone). Forty mothers and 10 fathers responded, with an average age of
      41. In the resuscitation room, 39 parents were accompanied by a health
      professional and 22 were given information about how the resuscitation room
      operated. The feelings most frequently reported by the parents were nervousness
      (39) and trust in the healthcare provided (20). All of the parents wished to be
      present. They felt that their presence was beneficial for the child (46), for
      themselves (50), and for the healthcare personnel (28).Conclusion: The experience
      of the parents in our resuscitation room is a positive one. Nevertheless, some
      aspects need to be improved, such as accompaniment of the parents and the
      information that they are provided. What is Known: * There is an international
      recommendation for parental presence during invasive procedures and
      cardiopulmonary resuscitation. * Few studies have been carried out on how parents
      in the resuscitation room feel and how they encounter the experience. What is
      New: * Even though most of the parents feel nervous in the resuscitation room,
      they expressed confidence in the medical team and they would wish to be present
      under similar circumstances.

PMID- 30196427
TI  - First-line therapies in metastatic colorectal cancer: integrating clinical
      benefit with the costs of drugs.
AB  - PURPOSE: In light of the relevant expenses of pharmacological interventions, it
      might be interesting to make a balance between the cost of the new drugs
      administered and the added value represented by the improvement in progression
      free survival (PFS) in first-line for metastatic colorectal cancer CRC (mCRC).
      METHODS: Phase III randomized controlled trials (RCTs) that compared at least two
      first-line chemotherapy regimens for mCRC patients were evaluated. Differences in
      PFS between the different arms were compared with the pharmacological costs (at
      the pharmacy of our hospital). The European Society for Medical Oncology
      Magnitude of Clinical Benefit Scale (ESMO-MCBS) was applied to the above RCTs.
      RESULTS: Overall 28 phase III RCTs, including 19,958 patients, were analyzed. The
      FOLFOX resulted the least expensive (56 ? per month of PFS gained) while the
      addition of irinotecan to FOLFOX (FOLFOXIRI) increased only marginally the costs
      (90 ? per month of PFS gained). Treatments including the monoclonal antibodies
      showed a cost per month of PFS gained of 2823 ? (FOLFIRI with cetuximab in KRAS
      wild-type patients and liver-only metastases), of ? 15,822 (FOLFOX with
      panitumumab in KRAS wild type), and of 13,383 ? (FOLFOX with bevacizumab).
      According to the ESMO-MCBS, the treatments including an EGFR-inhibitor (cetuximab
      or panitumumab) were associated with a score of 4, while the inclusion of
      bevacizumab reached a score of 3. CONCLUSIONS: Our data demonstrate a huge
      difference in cost per month of PFS gained in modern first-line treatments in
      mCRC.

PMID- 30196429
TI  - An integrated analysis of mRNA and sRNA transcriptional profiles in Coffea
      arabica L. roots: insights on nitrogen starvation responses.
AB  - Coffea arabica L. is an important agricultural commodity, accounting for 60% of
      traded coffee worldwide. Nitrogen (N) is a macronutrient that is usually limiting
      to plant yield; however, molecular mechanisms of plant acclimation to N
      limitation remain largely unknown in tropical woody crops. In this study, we
      investigated the transcriptome of coffee roots under N starvation, analyzing poly
      A+ libraries and small RNAs. We also evaluated the concentration of selected
      amino acids and N-source preferences in roots. Ammonium was preferentially taken
      up over nitrate, and asparagine and glutamate were the most abundant amino acids
      observed in coffee roots. We obtained 34,654 assembled contigs by mRNA
      sequencing, and validated the transcriptional profile of 12 genes by RT-qPCR.
      Illumina small RNA sequencing yielded 8,524,332 non-redundant reads, resulting in
      the identification of 86 microRNA families targeting 253 genes. The
      transcriptional pattern of eight miRNA families was also validated. To our
      knowledge, this is the first catalog of differentially regulated amino acids, N
      sources, mRNAs, and sRNAs in Arabica coffee roots.

PMID- 30196428
TI  - Management of Intraductal Papillary Mucinous Neoplasms: Controversies in
      Guidelines and Future Perspectives.
AB  - PURPOSE OF REVIEW: Management of intraductal papillary mucinous neoplasm (IPMN)
      is currently based on consensus, in the absence of evidence-based guidelines. In
      recent years, several consensus guidelines have been published, with distinct
      management strategies. In this review, we will discuss these discrepancies, in
      order to guide treating physicians in clinical management. RECENT FINDINGS: The
      detection rate of pancreatic cysts has increased substantially with the expanded
      use of high-quality imaging techniques to up to 45%. Of these cysts, 24-82% are
      IPMNs, which harbour a malignant potential. Timely detection of high-risk lesions
      is therefore of great importance. Surgical management is based on the presence of
      clinical and morphological high-risk features, yet the majority of resected
      specimens appear to be low risk. International collaboration and incentive large
      scale prospective registries of individuals undergoing cyst surveillance are
      needed to accumulate unbiased data and develop evidence-based guidelines.
      Additionally, development of non-invasive, accurate diagnostic tools (e.g.
      biomarkers) is needed to differentiate between neoplastic and non-neoplastic
      pancreatic cysts and detect malignant transformation at an early stage (i.e. high
      grade dysplasia).

PMID- 30196431
TI  - General intelligence is associated with working memory-related brain activity:
      new evidence from a large sample study.
AB  - Psychometric intelligence is closely related to working memory capacity. Here we
      aim to determine the associations of neural activation patterns during the N-back
      working memory paradigm with psychometric intelligence and working memory
      performance. We solved the statistical problems of previous studies using (1) a
      large cohort of 1235 young adults and (2) robust voxel-by-voxel permutation-based
      statistics at the whole-brain level. Many of the significant correlations were
      weak, and our findings were not consistent with those of previous studies. We
      observed that many of the significant correlations involved brain areas in the
      periphery or boundaries between the task-positive network (TPN) and task-negative
      network (TNN), suggesting that the expansion of the TPN or TNN is associated with
      greater cognitive ability. Lower activity in TPN and less task-induced
      deactivation (TID) in TNN were associated with greater cognitive ability. These
      findings indicate that subjects with greater cognitive ability have a lower brain
      response to task demand, consistent with the notion that TID in TNN reflects
      cognitive demand but partly inconsistent with the prevailing neural efficiency
      theory. One exception was the pre-supplementary motor area, which plays a key
      role in cognitive control and sequential processing. In this area, intelligent
      subjects demonstrated greater activity related to working memory, suggesting that
      the pre-supplementary motor area plays a unique role in the execution of working
      memory tasks in intelligent subjects.

PMID- 30196432
TI  - Stress-induced brain activation: buffering role of social behavior and neuronal
      nicotinic receptors.
AB  - Social behavior and stress responses both rely on activity in the prefrontal
      cortex (PFC) and amygdala. We previously reported that acute stress exposure
      impoverishes social repertoire and triggers behavioral rigidity, and that both
      effects are modulated by beta2-containing nicotinic receptors. We, therefore,
      hypothesized that the activity of brain regions associated with the integration
      of social cues will be modulated by stress exposure. We mapped the expression of
      c-fos protein in all subregions of the PFC and basolateral (BLA) and central (Ce)
      areas of the amygdala in C57BL/6J (B6) and beta2-/- mice. We show altered brain
      activity and differences in functional connectivity between the two genotypes
      after stress: the PFC and BLA were hyperactivated in B6 and hypo-activated in
      beta2-/- mice, showing that the impact of stress on brain activity and functional
      organization depends on the nicotinic system. We also show that the effects of
      the opportunity to explore a novel environment or interact socially after acute
      stress depended on genotype: exploration induced only marginal PFC activation in
      both genotypes relative to stress alone, excluding a major role for beta2
      receptors in this process. However, social interaction following stress only
      activated the rostral and caudolateral areas of the PFC in B6 mice, while it
      induced a kindling of activation in all PFC and amygdalar areas in beta2-/- mice.
      These results indicate that acute stress triggers important PFC-amygdala
      plasticity, social interaction has a buffering role during stress-induced brain
      activation, and beta2 receptors contribute to the effects of social interaction
      under stress.

PMID- 30196430
TI  - Distinct and complementary functions of rho kinase isoforms ROCK1 and ROCK2 in
      prefrontal cortex structural plasticity.
AB  - Rho-associated protein kinases (ROCK) 1 and 2 are attractive drug targets for a
      range of neurologic disorders; however, a critical barrier to ROCK-based
      therapeutics is ambiguity over whether there are isoform-specific roles for ROCKs
      in neuronal structural plasticity. Here, we used a genetics approach to address
      this long-standing question by analyzing both male and female adult ROCK1+/- and
      ROCK2+/- mice compared to littermate controls. Individual pyramidal neurons in
      the medial prefrontal cortex (mPFC) were targeted for iontophoretic
      microinjection of fluorescent dye, followed by high-resolution confocal
      microscopy and neuronal 3D reconstructions for morphometry analysis. Increased
      apical and basal dendritic length and intersections were observed in ROCK1+/- but
      not ROCK2+/- mice. Although dendritic spine densities were comparable among
      genotypes, apical spine length was decreased in ROCK1+/- but increased in ROCK2+/
      mice. Spine head and neck diameter were reduced similarly in ROCK1+/- and
      ROCK2+/- mice; however, certain spine morphologic subclasses were more affected
      than others in a genotype-dependent manner. Biochemical analyses of ROCK
      substrates in synaptic fractions revealed that phosphorylation of LIM kinase and
      cofilin were reduced in ROCK1+/- and ROCK2+/- mice, while phosphorylation of
      myosin light chain was decreased exclusively in ROCK1+/- mice. Collectively,
      these observations implicate ROCK1 as a novel regulatory factor of neuronal
      dendritic structure and detail distinct and complementary roles of ROCKs in mPFC
      dendritic spine structure.

PMID- 30196433
TI  - Hemiepiphysiodesis is a potentially effective surgical management for skeletally
      immature patients with patellofemoral instability associated with isolated genu
      valgum.
AB  - PURPOSE: Genu valgum is one of the well-known predisposing factors for
      patellofemoral instability. The study aims to investigate the outcomes of
      isolated hemiepiphysiodesis in the correction of genu valgum and in the
      management of recurrent patellofemoral instability. The hypothesis was that
      hemiepiphysiodesis alone would result in significant correction of genu valgum,
      thereby preventing recurrent patellofemoral instability. METHODS: In the cohort
      study, all skeletally immature patients who underwent isolated hemiepiphysiodesis
      for recurrent patellofemoral instability were included. All patients included in
      the study had a minimum of 1-year follow-up duration prior to the conclusion of
      the study. RESULTS: Sixteen of twenty knees had no further patellofemoral
      instability post-operatively. The change in the status of patellofemoral
      instability was statistically significant (p = 0.001), similar to the change in
      the tibiofemoral angle (p = 0.015) and patellar tilt angle (p = 0.002).
      Comparison between patients with and without patellofemoral instability post
      operatively revealed that the pre-operative patellar tilt angle (p = 0.005) and
      tibiofemoral angle (p = 0.001), post-operative patellar tilt angle (p = 0.004)
      and tibiofemoral angle (p = 0.027) as well as the change in patellar tilt angle
      (p = 0.001) and tibiofemoral angle (p = 0.001) were all significant predictors of
      the outcomes of genu valgum. CONCLUSION: Hemiepiphysiodesis is a potentially
      effective surgical management for skeletally immature patients with
      patellofemoral instability associated with isolated genu valgum. This is
      especially for patients who are skeletally immature and have sufficient remaining
      years for their genu valgum to be corrected using hemiepiphysiodesis. These
      patients also tended to have less severe genu valgum and patellar tilt angle,
      which could be corrected using hemiepiphysiodesis with the remaining years of
      growth. LEVEL OF EVIDENCE: II.

PMID- 30196434
TI  - Physiologic knee joint alignment and orientation can be restored by the minimally
      invasive double level osteotomy for osteoarthritic knees with severe varus
      deformity.
AB  - PURPOSE: The purpose of this study was to examine early radiological and clinical
      outcomes following minimally invasive double level osteotomy (DLO) procedure
      performed for osteoarthritic knees with severe varus deformity. METHODS: Twenty
      consecutive patients who underwent DLO for varus osteoarthritic knees were
      included in the study. All patients could be tracked for a minimum of 1 year.
      Periodical radiological and clinical evaluations were performed at 6 and 12
      months after surgery. In the radiological assessment, the following parameters
      were measured on full-length weight-bearing radiographs both pre- and
      postoperatively: mechanical tibiofemoral angle (mTFA), mechanical lateral distal
      femoral angle (mLDFA), mechanical medial proximal tibial angle (mMPTA), and joint
      line convergence angle (JLCA). In addition, subjective clinical results were
      evaluated using the Knee Injury and Osteoarthritis Outcome Score (KOOS) and the
      International Knee Documentation Committee (IKDC) Subjective Score. RESULTS: The
      mean age of the study population was 62.5 +/- 6.8 years (range 45-76 years). In
      the radiological evaluation, the preoperative mTFA, mLDFA, mMPTA, and JLCA values
      averaged 13.5 degrees  +/- 3.1 degrees  varus, 91.1 degrees  +/- 1.4 degrees ,
      82.3 degrees  +/- 2.0 degrees , and 5.8 degrees  +/- 2.3 degrees , respectively.
      At 6 and 12 months, all of the radiological parameters significantly improved and
      corrected to the values within normal range. In the clinical assessments at the
      follow-up evaluations, both the KOOS and IKDC subjective scores significantly
      improved from the preoperative values. No significant changes were noted between
      the 6 and 12-month results in the radiological and clinical assessments.
      CONCLUSIONS: The minimally invasive DLO technique is a valuable surgical
      technique accomplishing restoration of physiologic knee joint alignment and
      orientation with significant improvement in patient-registered clinical outcomes
      in early postoperative evaluation. Although the follow-up period is still short,
      the excellent clinical and radiological outcomes shown in the present study
      support the efficacy of this procedure. LEVEL OF EVIDENCE: Retrospective case
      series, Level IV.

PMID- 30196435
TI  - Deterioration of patellofemoral cartilage status after medial open-wedge high
      tibial osteotomy.
AB  - PURPOSE: To identify parameters associated with deterioration of patellofemoral
      (PF) cartilage after open-wedge high tibial osteotomy (OWHTO) and determine
      predictive values. It was hypothesized that cartilage injuries in PF joints would
      progress after OWHTO in patients who need a large alignment correction. METHODS:
      Fifty-two knees in 47 patients who underwent bi-planer OWHTO for the treatment of
      medial compartment osteoarthritis from 2012 to 2017 and received a second-look
      arthroscopy at the time of plate removal (mean 14 months post-OWHTO) were
      assessed. Clinical outcomes were evaluated by the Knee Society Scores. Cartilage
      status in PF joints were evaluated arthroscopically using the International
      Cartilage Repair Society (ICRS) grading system. Patients were divided into two
      groups and patients who had progressed PF cartilage injury (progressed group)
      were compared with those who did not have progressed PF cartilage injuries (non
      progressed group) using various parameters. The relationships between medial
      opening gap or change in the medial proximal tibial angle (DeltamPTA) and
      progression of PF cartilage injuries were examined by receiver operating
      characteristic (ROC) curve analysis. RESULTS: The mean Knee Society Scores were
      significantly improved after surgery (P < 0.01). The grades for the patella and
      trochlea progressed in 12 (23.0%) and 16 knees (30.8%), respectively. The mean
      preoperative hip-knee-ankle (HKA) angle, mechanical axis, and mPTA in the
      progressed group were significantly smaller than those in the non-progressed
      group (P < 0.01). The mean medial opening gap and DeltamPTA in the progressed
      group were significantly larger than those in the non-progressed group (P <
      0.01). ROC curve analysis showed that the cut-off values of the medial opening
      gap and DeltamPTA for progression of PF cartilage injuries were 13 mm and 9
      degrees , respectively. Progression of PF cartilage injuries was more frequently
      observed in knees with a medial opening gap >= 13 mm (P = 0.019, odds ratio =
      4.60) or a DeltamPTA >= 9 degrees  (P = 0.003, odds ratio 6.93) than knees with
      those of < 13 mm or 9 degrees , respectively. CONCLUSIONS: Cartilage injuries in
      PF joints tended to progress after OWHTO in patients with medial opening gap >=
      13 mm or DeltamPTA >= 9 degrees . If medial opening gap is >= 13 mm or DeltamPTA
      is >= 9 degrees  in planning for OWHTO, other type of surgery may need to be
      considered to avoid early progression of PF cartilage injuries. LEVEL OF
      EVIDENCE: Level IV, therapeutic case series.

PMID- 30196436
TI  - Inferior graft maturity in the PL bundle after autograft hamstring double-bundle
      ACL reconstruction.
AB  - PURPOSE: The purpose of this study was to evaluate the signal/noise quotient
      (SNQ) for graft maturation and the serial changes observed in the magnetic
      resonance imaging (MRI) findings after double-bundle (DB) anterior cruciate
      ligament (ACL) reconstruction using a hamstring tendon autograft at a minimum of
      5 years after surgery. METHODS: Forty-five patients who underwent DB ACL
      reconstruction between 2007 and 2010 were included in this prospective study. All
      participants underwent postoperative MRI at 3 weeks and 3, 6, 9 and 12, 18, 24,
      36, 48 and 50 months. The signal intensity (SI) characteristics of the
      reconstructed graft were evaluated on oblique axial proton density-weighted MR
      imaging (PDWI) perpendicular to the grafts. The signal/noise quotient (SNQ) was
      calculated to quantitatively determine the normalized SI. The SNQ of the AMB and
      PLB was evaluated separately. RESULTS: The mean SNQ of the AM bundle (AMB)
      continued to increase until 6 months after surgery (5.2 +/- 1.2), and then
      gradually decreased and became well stabilized by 18 months (3.3 +/- 0.5), after
      which it remained unchanged. On the other hand, the mean SNQ of the PL bundle
      (PLB) continued to increase until 9 months after surgery (6.2 +/- 1.1), and then
      decreased incrementally and became well stabilized by 24 months (4.1 +/- 0.5).
      The SI of PLB was significantly higher than that of AMB between 3 and 24 months
      (p = 0.04, 0.03, 0.01, 0.04, 0.02 and 0.03, respectively). CONCLUSIONS: These
      results indicate that at least 18 months is needed after ACL reconstruction to
      sufficiently restore the SI of the AMB, while at least 24 months are needed to
      for the PLB. The SI of the PLB was significantly higher than that of the AMB at 3
      24 months after surgery, indicating that the PLB showed inferior graft maturity
      to the AMB until 24 months after surgery. For clinical relevance, the correct
      understanding of serial changes in graft maturation may potentially be used in
      decision-making regarding a return to sports. LEVEL OF EVIDENCE: Prospective case
      series, Level IV.

PMID- 30196437
TI  - Increasing the deltoid muscle volume positively affects functional outcomes after
      arthroscopic rotator cuff repair.
AB  - PURPOSE: The aim of this study was to determine the effect of changes in deltoid
      muscle volume (DMV) on the clinical outcomes of patients who underwent
      arthroscopic repair due to chronic rotator cuff rupture. METHODS: A total of 54
      patients (35 females, 19 males) between 40 and 70 years of age who underwent
      single-row arthroscopic repair due to chronic rotator cuff tears were compared
      via preoperative (preop) and postoperative (postop) (6-12 months) magnetic
      resonance imaging (MRI) to determine the total DMV (tDMV). A clinical evaluation
      was performed with American Shoulder and Elbow Surgeons (ASES) and Constant
      scores in both the preop and postop groups. tDMV values were also measured in a
      randomly selected control group (50 patients). A standardized rehabilitation
      program was recommended for all patients. RESULTS: Positive correlations were
      found between the change in tDMV (DeltatDMV) and ASES and Constant scores (p <
      0.03 and p < 0.032, respectively). The preop tDMV value was significantly lower
      in the patient group than in the control group (p < 0.02). Significantly lower
      DeltatDMV and body mass index (BMI)-adjusted tDMV values [Delta(tDMV/BMI)] were
      observed in patients who had rerupture at the postop MRI. CONCLUSIONS: According
      to the present study, changes in DMV impact clinical outcomes after rotator cuff
      repair. Rehabilitation of the DMV or increasing the preop DMV values positively
      affects postop clinical outcomes. In addition, if the DMV is below the cutoff
      value during the preop period, there is insufficient improvement in clinical
      scores. The clinical relevance of this study is the finding that in patients with
      a chronic rotator cuff tear and a hypotrophic deltoid muscle, increasing the
      preop DMV could help achieve better functional outcomes. LEVEL OF EVIDENCE:
      Prognostic, Level 3, case-control study.

PMID- 30196438
TI  - What Is the Role of Additional Pharmacotherapy and Neuromodulation in Patients
      with Marginal Benefit from Botulinum Toxin Injection?
AB  - PURPOSE OF REVIEW: Third-line therapies for patients with overactive bladder
      (OAB) can improve symptoms for those who have failed conservative therapies.
      Options include percutaneous tibial nerve stimulation (PTNS), cystoscopic
      injection of onabotulinumtoxinA (BTX-A), and sacral neuromodulation (SNM). This
      paper aims to review the current literature on the treatment of patients with
      idiopathic OAB who have undergone BTX-A injections and have not responded or have
      undesirable side effects from the therapy. RECENT FINDINGS: There are no
      randomized control trials examining the role of concurrent medical therapy and
      BTX-A; rather, there are observational studies in the neurogenic population.
      Furthermore, there are two observational studies on the role of SNM in BTX-A
      refractory idiopathic OAB patients demonstrating its safety and efficacy. There
      are many options available to the patient who fails BTX-A. Further research in
      this specific patient population is necessary to determine why patients have
      suboptimal responses and to delineate the next step in treatment.

PMID- 30196439
TI  - Correction to: The impact of different doses of indocyanine green on the sentinel
      lymph-node mapping in early stage endometrial cancer.
AB  - Unfortunately, the P value at multivariate analysis for ICG concentration in
      Table 3 was incorrectly published.

PMID- 30196440
TI  - Visualize and quantify the structural alteration of the rat spinal cord injury
      based on multiphoton microscopy.
AB  - The development of imaging technique to visualize and quantify the structural
      alteration of the spinal cord injury (SCI) may lead to better understanding and
      treatments of the injuries. In this work, multiphoton microscopy (MPM) based on
      two-photon excited fluorescence (TPEF) and second-harmonic generation (SHG) was
      tentatively applied to quantitatively visualize the cellular microstructures of
      SCI to demonstrate the feasibility and superiority of MPM in SCI imaging. High
      contrast MPM images of normal and injured spinal cord tissue were obtained for
      comparison. Moreover, the changes of injured spinal cord were characterized by
      the quantitative analysis of the MPM images. These results showed that MPM
      combined with quantitative method has the ability to identify the characteristics
      of spinal cord injury including the changes in the contents of nerve fibers and
      extracellular matrix. With the advancement of MPM, we believe that this technique
      has great potential to provide the histological diagnosis for the monitoring and
      evaluation of SCI.

PMID- 30196441
TI  - The growth of Pichia pastoris Mut+ on methanol-glycerol mixtures fits to
      interactive dual-limited kinetics: model development and application to optimised
      fed-batch operation for heterologous protein production.
AB  - The methanol-glycerol co-feeding during the induction stage for heterologous
      protein production in Pichia pastoris has shown significant productive
      applications. Available model analysis applied to this dual-limited condition is
      scarce and normally does not consider the interaction effects between the
      substrates. In this work, a dual-limited growth model of P. pastoris considering
      an interactive kinetic effect was applied to an optimised fed-batch process
      production of heterologous Rhizopus oryzae lipase (ROL). In the proposed model,
      the growth kinetics on glycerol is fully expressed, whereas methanol kinetics is
      modulated by the co-metabolisation of glycerol, resulting in an enhancing effect
      of glycerol-specific growth rate. The modelling approach of fed-batch cultures
      also included the methanol volatilisation caused by the aeration that was found
      to be a not-negligible phenomenon. The model predicts the ability of P. pastoris
      to keep control of the methanol concentration in the broth during ROL-optimised
      production process in fed batch and fits satisfactorily the specific cell growth
      rate and ROL production. Implications of interaction effect are discussed
      applying the general procedure of modelling approach.

PMID- 30196442
TI  - Subcutaneous internal anterior fixation of pelvis fractures-which configuration
      of the InFix is clinically optimal?-a retrospective study.
AB  - INTRODUCTION: Subcutaneous internal fixation (InFix) has become a valid
      alternative for anterior fixation of pelvic ring injuries. Complications
      associated with this technique are lateral femoral cutaneous nerve (LFCN)
      irritation and anterior thigh pain due to prominent implants. The aim of this
      study was to identify a configuration of the InFix that causes the least adverse
      side effects. METHODS: Nineteen patients (6 females, mean age 61 years) with 38
      hemipelves were included. Rod-to-bone distance and symphysis-rod distance were
      measured on AP- and outlet- radiographs. These distances were analyzed in
      relation to the primary outcomes: early removal of the InFix, post-operative
      complications and damage of the LFCN. RESULTS: Regarding rod-to-bone distance, a
      distance of 20 to 25 mm causes less complications, LFCN damage and no early
      removals of the InFix. Symphysis-to-rod distance analysis showed the best results
      regarding LFCN damage and other complications when the rod had a distance of less
      than 40 mm to the symphysis. A distance more than 40 mm was associated with fewer
      early removal of the InFix. CONCLUSIONS: Planned optimized configuration of the
      InFix with a rod-to-bone distance between 20 and 25 mm may reduce postoperative
      complications. Regarding LFCN damage, the rod-to-symphysis distance should not be
      more than 40 mm.

PMID- 30196443
TI  - Conventional versus computer-assisted surgery in total knee arthroplasty:
      comparison at ten years follow-up.
AB  - PURPOSE: Computer-assisted systems (CAS) for total knee arthroplasty (TKA) were
      expected to result in more accurate prosthesis implantation, better patient
      outcomes, and longer implant survival when compared to conventional
      instrumentation (CI). The aim of this study was to compare two groups of patients
      operated using CAS or CI at ten years follow-up. METHODS: One hundred twenty TKA
      patients, 60 using CAS and 60 using CI, were contacted after a decade for follow
      up. Eligible patients received radiological examination to assess the lower-limb
      mechanical axis. They were also clinically assessed using the Knee Injury and
      Osteoarthritis Outcome Score (KOOS) and the Knee Society Score for Knee (KSS-K)
      and Function (KSS-F) Scoring. Kaplan-Meier survival analysis was performed to
      assess revisions, not for post-traumatic reasons. RESULTS: In CAS and CI groups,
      the lower-limb mechanical axis was 1.7 degrees  +/- 2.4 degrees  and 1.5 degrees 
      +/- 2.8 degrees , respectively; corresponding KOOS values were 82.3 +/- 14.3 and
      78.6 +/- 14.4; KSS-K values were 85.9 +/- 11.1 and 85.0 +/- 9.7; KSS-F values
      were 82.2 +/- 19.3 and 83.8 +/- 18. For these assessments, the differences
      between the two groups were not statistically significant (p > 0.05). Two CAS
      (3.8%) and three CI patients (5.7%) were revised. The Kaplan-Meier analysis
      showed no significant differences between the two groups. CONCLUSIONS: No
      significant differences were found at long-term follow-up in terms of
      radiographical-clinical outcomes and of implant survival between TKA operated
      using CAS or CI.

PMID- 30196444
TI  - National registry of hemoglobinopathies in Greece: updated demographics, current
      trends in affected births, and causes of mortality.
AB  - National registries constitute an invaluable source of information and contribute
      to the improvement of hemoglobinopathy management. Herein, we present the second
      updated report of the National Registry for Haemoglobinopathies in Greece (NRHG)
      and critically discuss the time trends in demographics, affected births, and
      causes of mortality. Thirty-eight Greek hemoglobinopathy units reported data from
      diagnosis to the last follow-up or death by retrospectively completing an
      electronic form. Four thousand thirty-two patients were eligible for inclusion;
      more than half of them had thalassaemia major. Compared to the previous report, a
      reduction in the total number of all hemoglobinopathies except for
      hemoglobinopathy "Eta" was evident. The total number of affected births was also
      reduced; most of them were attributable to diagnostic errors and lack of
      awareness. Importantly, data on iron overload are reported for the first time;
      although most patients had low or moderate liver iron concentration (LIC) values,
      a non-negligible proportion of patients had high LIC. The burden due to heart
      iron overload was less prominent. Cardiac- and liver-related complications are
      the major causes of morbidity and mortality. From 2000 to 2015, a decrease in
      heart-related deaths along with an increase in liver-associated fatalities was
      observed. The Hellenic Prevention Program along with advances in chelation
      regimens and iron status monitoring have resulted in improved patient outcomes.
      The NRHG gives insight into the effectiveness of prevention programs, the
      therapeutic management of hemoglobinopathies and associated outcomes. NRHG may
      contribute to the formulation of a roadmap for hemoglobinopathies in Europe and
      promote the implementation of effective public health policies.

PMID- 30196445
TI  - Trehalose-Induced Variation in Physical Properties of Fluidic Lipid Bilayer.
AB  - The effect of the trehalose on the physical properties of the fluidic lipid
      bilayer was studied using surface plasmon resonance (SPR) and cyclic voltammetry
      (CV). The bilayer was fabricated by tethering 1,2-dipalmitoyl-sn-glycero-3
      phosphothioethanol on a gold surface to form a monolayer and then using liposomes
      to adsorb an upper layer on the tethered monolayer. The liposomes were prepared
      with a desired ratio (mol/mol) of trehalose to lipid, before the adsorption was
      performed. The formation of the adsorbed layer was monitored with SPR, and the
      SPR responses were converted to the surface density of the layer. In addition,
      the CV measurement was conducted to acquire the current-potential responses to
      evaluate the charge permeability of the layer. The surface density was gradually
      increased with the trehalose ratio up to 0.5, while the charge permeability was
      decreased. From these changes, the trehalose appears to be related to the
      curvature generation induced by the trehalose, which is consistent with the
      previous simulation results. In the identical measurements at glucose, little
      change in the properties was observed with even up to 2:1 ratio of glucose:lipid.
      These results seem attributed to the osmotic and volumetric effect on the
      headgroup packing disruption. The present study may provide a unique platform to
      control biological functions related to cellular processes.

PMID- 30196446
TI  - 1,2-Diarylethylamine- and Ketamine-Based New Psychoactive Substances.
AB  - While phencyclidine (PCP) and ketamine remain the most well-studied and widely
      known dissociative drugs, a number of other agents have appeared since the late
      1950s and early 1960s, when the pharmacological potential of this class was first
      realized. For example, hundreds of compounds have been pursued as part of
      legitimate research efforts to explore these agents. Some of these found their
      way out of the research labs and onto illicit markets of the 1960s and following
      decades as PCP analogs. Other "illicit analogs" apparently never appeared in the
      scientific literature prior to their existence on clandestine markets, thus
      originating as novel innovations in the minds of clandestine chemists and their
      colleagues. Like so much else in this world, new technologies changed this
      dynamic. In the 1990s individuals separated by vast geographical distances could
      now communicate nearly instantaneously with ease through the Internet. Some
      individuals used this newly found opportunity to discuss the chemistry and
      psychoactive effects of dissociative drugs as well as to collaborate on the
      design and development of novel dissociative compounds. Similar to modern
      pharmaceutical companies and academic researchers, these seekers tinkered with
      the structure of their leads pursuing goals such as improved duration of action,
      analgesic effects, and reduced toxicity. Whether all these goals were achieved
      for any individual compound remains to be seen, but their creations have been let
      out of the bag and are now materialized as defined compositions of matter.
      Moreover, these creations now exist not only in and of themselves but live on
      further as permutations into various novel analogs and derivatives. In some cases
      these compounds have made their way to academic labs where potential clinical
      applications have been identified. These compounds reached wider distribution
      when other individuals picked up on these discussions and began to market them as
      "research chemicals" or "legal highs". The result is a continuously evolving game
      that is being played between legislatures, law enforcement, and research chemical
      market players. Two structurally distinct classes that have appeared as
      dissociative-based new psychoactive substances (NPS) are the 1,2
      diarylethylamines and beta-keto-arylcyclohexylamines. Examples of the former
      include diphenidine and various analogs such as fluorolintane and N-ethyl
      lanicemine, and examples of the latter are analogs of ketamine such as
      methoxetamine, deschloroketamine, and 2-fluoro-2-deschloroketamine. The subject
      of this chapter is the introduction to some of the dissociative NPS from these
      classes and their known pharmacology that have emerged on the market in recent
      years.

PMID- 30196447
TI  - Resistance training in young men induces muscle transcriptome-wide changes
      associated with muscle structure and metabolism refining the response to exercise
      induced stress.
AB  - BACKGROUND: Gene expression is an important process underpinning the acute and
      chronic adaptive response to resistance exercise (RE) training. PURPOSE: To
      investigate the effect of training status on vastus lateralis muscle global
      transcriptome at rest and following acute RE. METHODS: Muscle biopsies of nine
      young men (age: 26(2) years; body mass: 69(9) kg; height 172(6) cm) who undertook
      RE training for 10 weeks were collected pre and 24 h post-RE in the untrained
      (W1) and trained (W10) states and analysed using microarray. Tests of
      differential expression were conducted for rested and after RE contrasts in both
      training states. To control for false discovery rate (FDR), multiple testing
      correction was performed at a cut-off of FDR < 0.05. RESULTS: Unaccustomed RE (at
      W1) upregulated muscle gene transcripts related to stress (e.g., heat shock
      proteins), damage and inflammation, structural remodelling, protein turnover and
      increased translational capacity. Trained muscles (at W10) showed changes in the
      transcriptome signature regarding the regulation of energy metabolism, favouring
      a more oxidative one, upregulated antioxidant- and immune-related genes/terms,
      and gene transcripts related to the cytoskeleton and extracellular matrix, muscle
      contraction, development and growth. CONCLUSIONS: These results highlight that
      chronic repetition of RE changes muscle transcriptome response towards a more
      refined response to RE-induced stress.

PMID- 30196448
TI  - The influence of alkalosis on repeated high-intensity exercise performance and
      acid-base balance recovery in acute moderate hypoxic conditions.
AB  - PURPOSE: Exacerbated hydrogen cation (H+) production is suggested to be a key
      determinant of fatigue in acute hypoxic conditions. This study, therefore,
      investigated the effects of NaHCO3 ingestion on repeated 4 km TT cycling
      performance and post-exercise acid-base balance recovery in acute moderate
      hypoxic conditions. METHODS: Ten male trained cyclists completed four repeats of
      2 * 4 km cycling time trials (TT1 and TT2) with 40 min passive recovery, each on
      different days. Each TT series was preceded by supplementation of one of the 0.2
      g kg-1 BM NaHCO3 (SBC2), 0.3 g kg-1 BM NaHCO3 (SBC3), or a taste-matched placebo
      (0.07 g kg-1 BM sodium chloride; PLA), administered in a randomized order.
      Supplements were administered at a pre-determined individual time to peak
      capillary blood bicarbonate concentration ([HCO3-]). Each TT series was also
      completed in a normobaric hypoxic chamber set at 14.5% FiO2 (~ 3000 m). RESULTS:
      Performance was improved following SBC3 in both TT1 (400.2 +/- 24.1 vs. 405.9 +/-
      26.0 s; p = 0.03) and TT2 (407.2 +/- 29.2 vs. 413.2 +/- 30.8 s; p = 0.01)
      compared to PLA, displaying a very likely benefit in each bout. Compared to SBC2,
      a likely and possible benefit was also observed following SBC3 in TT1 (402.3 +/-
      26.5 s; p = 0.15) and TT2 (410.3 +/- 30.8 s; p = 0.44), respectively. One
      participant displayed an ergolytic effect following SBC3, likely because of
      severe gastrointestinal discomfort, as SBC2 still provided ergogenic effects.
      CONCLUSION: NaHCO3 ingestion improves repeated exercise performance in acute
      hypoxic conditions, although the optimal dose is likely to be 0.3 g kg-1 BM.

PMID- 30196449
TI  - Exploring the effect of exercise training on testicular function.
AB  - PURPOSE: The impact of exercise training on testicular function is relatively ill
      defined. To gain new insights into this important topic, published data, deriving
      from both humans and animal studies, were critically analyzed. RESULTS AND
      CONCLUSIONS: The effects of exercise on the hypothalamus-pituitary-gonadal axis,
      influenced by the type, intensity and duration of the exercise program, can be
      evaluated in terms of total and free testosterone and/or luteinizing hormone and
      follicle-stimulating hormone serum levels and sperm parameters. High-intensity
      exercise promotes a common decrease in these parameters, and therefore,
      negatively impacts upon testicular function. However, published data for moderate
      intensity exercise training are inconsistent. Conversely, there is consistent
      evidence to support the benefits of exercise training to prevent and/or
      counteract the impairment of testis function caused by aging, obesity and
      doxorubicin treatment. This positive effect is likely the consequence of
      decreased oxidative stress and inflammatory status. In the future, it will be
      important to clarify the molecular mechanisms which explain these reported
      discrepancies and to establish guidelines for an active lifestyle to promote
      healthy testicular function.

PMID- 30196451
TI  - The effects of breed, season and parity on the reproductive performance of pigs
      reared under hot and humid environments.
AB  - A research aimed at evaluating the reproductive performance of pigs as influenced
      by breed, season, and parity was carried out. Reproductive performance records of
      1383 sows made up of 204 primiparous and 1179 multiparous large white (687) and
      Duroc * large white crosses (696) obtained over a 3-year period (2013 to 2016)
      were used. Data on reproductive performance taken were farrowing rate, litter
      size at birth and at weaning, piglet weight at birth and at weaning farrowing
      interval and pre-weaning mortality. To determine the effect of season, parity and
      breed on reproductive performance, the 4-way analysis of variance (ANOVA) was
      used. A mixed model was fitted using the generalized linear model (GLM) procedure
      of the GenStat (Discovery Edition) to investigate the fixed effects of breed (two
      classes), season of birth (three classes) and parity (five classes) on the
      reproductive traits. Where differences in means were observed, the means were
      separated using the least significant difference at 5% level of significance.
      Results obtained indicated litter size at birth of 12.5 +/- 0.3 and 14.2 +/- 0.5
      for the large white and the Duroc * large white respectively and farrowing rates
      of 90.0 +/- 2.3 and 94.5 +/- 2.5% for the large white and the Duroc * large white
      respectively. Litter size at birth and at weaning, farrowing rate and piglet
      weight at birth were all influenced by parity and season with increasing parity
      significantly reducing litter size at birth and at weaning. Reproductive traits
      of the sows were superior during the rainy season, an indication of the need to
      consider season of birth in making decision.

PMID- 30196450
TI  - Trends in hospital admission for acute diverticulitis in Italy from 2008 to 2015.
AB  - BACKGROUND: Epidemiological studies in Western countries have documented an
      increase of hospitalizations for acute diverticulitis (AD) but Italian evidence
      is scarce. The aim of the present study was to analyse the trend in
      hospitalization for AD, including in-hospital mortality, in Italy from 2008 to
      2015. METHODS: Through the Italian Hospital Information System of the National
      Health System, we identified diverticulitis of the colon as a discharge
      diagnosis. Age- and gender-specific rates of hospitalization for AD were
      assessed. RESULTS: 174,436 hospitalizations were identified with an increasing
      rate in 2008-2015 from 39 to 48 per 100,000 inhabitants (p < 0.001). The rate of
      hospitalization was higher for women, but the increasing trend over time was even
      more pronounced among men (mean increase per year 3.9% and 2.1% among men and
      women, respectively) (p < 0.001). The increased rate of hospitalization was
      accounted for by patients less than 70 years old, especially those under 60. In
      contrast, the hospitalization rate for older patients (age >= 70 years) was
      higher but remained unchanged during the study period. The number of patients
      with one hospital admissions was significantly higher than the number of patients
      with at least two hospitalizations (p < 0.001) and both groups showed a
      significant and comparable increase year by year. The overall in-hospital
      mortality rate increased from 1.2 to 1.5% (p = 0.017). More specifically, the
      increase was observed in patients at their first hospitalization [from 1 to 1.4%
      (mean increase per year of 3%, p = 0.003)]. An increase in mortality was most
      evident among women (from 1.4 to 1.8% p = 0.025) and in older patients [age 70-79
      years from 1.2 to 1.7% (p = 0.034), >= 80 years from 2.9 to 4% (p = 0.001)].
      CONCLUSIONS: In Italy, between 2008 and 2015, the rate of hospitalization for AD
      has been constantly increasing due to the hospitalization of younger individuals,
      especially men. There was a significant increase of in-hospital mortality
      especially among women, elderly and during the first hospitalization. These
      findings suggest the need for increased awareness and clinical skills in the
      management of this common condition.

PMID- 30196452
TI  - Influence of dislocations, twins, and stacking faults on the fracture behavior of
      nanocrystalline Ni nanowire under constant bending load: a molecular dynamics
      study.
AB  - In this paper, constant load bending tests were performed on a nanocrystalline Ni
      nanowire specimen at different deformation temperatures using molecular dynamics
      simulation to investigate deformation behavior and mechanisms responsible for
      fracture. The nature of the fracture occurred in this nanowire specimen is found
      to transit from brittle to ductile as the temperature rises from 500 to 800 K.
      Also, with an increase in temperature, the fracture strain is increased
      indicating more plastic deformation prior to fracture. In the case of 500 K and
      600 K deformation temperatures, fracture occurred along the shear band due to
      slip-twin interaction. On the other hand, at comparatively higher deformation
      temperatures, such as 700 K and 800 K, twinning and detwinning mechanisms are
      responsible for accommodating large plastic strain before fracture thus imparting
      plasticity in the specimen. It has also been found that formation and collapse of
      the stacking fault tetrahedron causes fracture of nanocrystalline Ni nanowire at
      800 K.

PMID- 30196453
TI  - A phantom based evaluation of vessel lumen area quantification for coronary CT
      angiography.
AB  - Coronary computed tomography (CT) angiography is a noninvasive method for
      visualizing coronary artery disease. However, coronary CT angiography is limited
      in assessment of stenosis severity by the partial volume effect and
      calcification. Therefore, an accurate method for assessment of stenosis severity
      is needed. A 10 cm diameter cylindrical Lucite phantom with holes in the range of
      0.4-4.5 mm diameter was fitted in a chest phantom. The holes were filled with an
      iodine solution of 8 mg/mL. To simulate coronary artery disease, different levels
      of stenosis were created by inserting Lucite rods into the holes with diameter
      range of 2-4.5 mm. The resulting lumen cross sectional areas ranged from 1.4 to
      12.3 mm2. To simulate arterial calcification, calcium hydroxyapatite rods were
      inserted into the holes with diameter range of 2-4.5 mm. Images of the phantoms
      were acquired at 100 kVp using a 320-slice CT scanner. A maual and a semi
      automated technique based on integrated Hounsfield units was used to calculate
      vessel cross-sectional area. There was an excellent correlation between the
      measured and the known cross-sectional area for both normal and stenotic vessels
      using the manual and the semi-automated techniques. However, the overall
      measurement error for the manual method was more than twice as compared with the
      integrated HU technique. Determination of vessel lumen area using the semi
      automated integrated Hounsfield unit technique yields more than a factor of two
      improvement in precision and accuracy as compared to the existing manual
      technique for vessels with and without stenosis. This technique can also be used
      to accurately measure arterial cross-sectional area in the presence of coronary
      calcification.

PMID- 30196454
TI  - Rational design-based engineering of a thermostable phytase by site-directed
      mutagenesis.
AB  - Phytases are enzymes that hydrolysis phytic acid and makes mineral phosphorus
      available to animals. Phytases face relatively extreme heating during food
      processing, thus thermostability plays an important role in industrial
      applicability of this enzyme. Herein, we report the design of a thermostable
      phytase with favorable biochemical properties and high enzymatic activity using
      molecular dynamics and rational design-based molecular engineering. Based on the
      crystal structure of E. coli phytase, bioinformatics analysis and docking binding
      energy measurement, S392F mutant was introduced by site-directed mutagenesis in
      order to improve thermostability of phytase through strengthen the bounding
      interactions. Wilde type and Mutated constructs were expressed in E. coli BL 21.
      The WT and manipulated phytase were purified; their biochemical and kinetic was
      investigated. Results revealed that recombinant WT and mutant phytase have
      optimum temperature of 50  degrees C with no significance change but optimum pH
      of WT and mutant was respectively 5 and 6 with a pH shift. Furthermore, S392F
      phytase catalytic efficiency values showed significant improve of 25.6%, compared
      with the WT. Analysis of the retained enzymatic activity at high temperatures,
      indicated that despite of phytase stability reduction at high temperatures but
      mutant phytase showed more stable behavior in compare with WT phytase, So that at
      70  degrees C showed twice thermo stability and at 80  degrees C and 90  degrees
      C display respectively 74% and 78.4% improvement of thermostability compared to
      the wild-type. In conclusion, our results implied that the designed phytase could
      be a potential candidate for phytase manipulation research and industrial
      applications with improved thermostability.

PMID- 30196455
TI  - Plant stem cells: what we know and what is anticipated.
AB  - Plant stem cell research is of interest due to stem cells ability of unlimited
      division, therapeutic potential and steady supply to provide precursor cells.
      Their isolation and culture provides the important source for the production of
      homogenous lines of active constituents that allow large-scale production of
      various metabolites. The process of dedifferentiation and reversal to pluripotent
      cells involves the various pathways genes related to the stem cells and are
      associated to each other for maintaining a specific niche. Domains such as niche
      dynamics and maintenance signaling can be used for the identification of genes
      for stem cell niche. Significant findings have been achieved in the past on plant
      stem cells however our understanding towards mechanisms underlying some specific
      phenomenon like dedifferentiation, regulation, niche dynamics is still in
      infancy. The present review is based on the past research efforts and also pave a
      way forward for the future anticipation in the field of development of cell
      cultures for the production of active metabolites on large scale and undertanding
      transcriptional regulation of stem cell genes involved in niche signaling.

PMID- 30196456
TI  - Isolation and characterization of nine microsatellite markers for the red alga
      Corallina officinalis.
AB  - We report the development of nine polymorphic microsatellite markers for
      Corallina officinalis (Linnaeus, 1758), a calcifying intertidal red alga and
      important ecosystem engineer spread along the North East Atlantic.
      Characterization and analysis of loci were made using 15 individuals of C.
      officinalis from populations in Iceland and the UK. The average number of alleles
      per locus was 3.78 (range 2-6) and mean of gene diversity was 0.58 (range 0.38
      0.77). The set of microsatellites developed here will provide a useful molecular
      tool for population genetic and conservation studies.

PMID- 30196457
TI  - Correction to: Antimicrobial resistance and the presence of extended-spectrum
      beta-lactamase genes in Escherichia coli isolated from the environment of horse
      riding centers.
AB  - The original publication of this paper contains a mistake.

PMID- 30196459
TI  - Performance of a kerb side inlet to irrigate street trees and to improve road
      runoff water quality: a comparison of four media types.
AB  - The TREENET inlet is an emerging water-sensitive urban design technology that
      consists of a novel kerb side inlet coupled with a leaky well infiltration
      system. The inlets have been retrofitted to existing roads since 2006; however,
      there is currently little information available on the effectiveness of these
      inlet and leaky well systems. This study investigated the performance of the kerb
      side inlets and leaky well system for water quality improvement prior to
      infiltration to native soil. The leaky wells included four filter media types,
      namely gravel, water treatment solids, sandy loam and clay. To compare the
      performance of the four filter media types, batch and column studies were
      performed in the laboratory. The best performance was observed using the sandy
      loam as a filter media, followed by clay, water treatment solids and then gravel.
      The selection of effective media for removal of heavy metals is important as each
      media type has different pollutant removal capacity, infiltration and clogging
      performance.

PMID- 30196458
TI  - Fenton oxidation of municipal secondary effluent: comparison of Fe/Ce-RGO
      (reduced graphene oxide) and Fe2+ as catalysts.
AB  - The advanced treatment of municipal secondary effluent by heterogeneous and
      homogeneous Fenton processes using Fe/Ce-RGO (reduced graphene oxide) and Fe2+ as
      catalysts was studied and compared. Sulfamethazine (SMT) was spiked in the
      effluent to examine the effectiveness of the emerging contaminant removal. The
      Fe/Ce-RGO catalyst was characterized using a scanning electron microscope (SEM)
      and cycle voltammetry curves. The removal of dissolved organic carbon (DOC),
      soluble chemical oxygen demand (SCOD), SMT, and ultraviolet-visible spectroscopy
      in 254 nm (UV254) of municipal secondary effluents was examined. The DOC removal
      efficiency of secondary effluent (without addition of SMT) was 36.30% and 11.74%
      using Fe/Ce-RGO and Fe2+ as catalysts, respectively. The removal efficiency of
      DOC, SCOD, and SMT in heterogeneous Fenton process was higher than that in
      homogeneous Fenton process. The changes of three-dimensional excitation-emission
      matrix (3DEEM) fluorescence, soluble microbial products (SMPs), humic acids, and
      UV254 were determined, and the results indicated that UV254, aromatic proteins,
      and humic acids decreased rapidly in both processes; however, polysaccharides and
      protein-like substances were difficult to degrade. Although some toxic substances
      produced after Fenton-like treatment, the biodegradability of the treated
      effluent was enhanced.

PMID- 30196460
TI  - Selenate tolerance and selenium hyperaccumulation in the monocot giant reed
      (Arundo donax), a biomass crop plant with phytoremediation potential.
AB  - The response of giant reed (Arundo donax L.) to selenium (Se), added as selenate,
      was studied. The development, stress response, uptake, translocation, and
      accumulation of Se were documented in three giant reed ecotypes STM (Hungary), BL
      (USA), and ESP (Spain), representing different climatic zones. Plantlets
      regenerated from sterile tissue cultures were grown under greenhouse conditions
      in sand supplemented with 0, 2.5, 5, and 10 mg Se kg-1 added as sodium selenate.
      Total Se content was measured in different plant parts using hydride generation
      atomic fluorescence spectroscopy. All plants developed normally in the 0-5.0 mg
      Se kg-1 concentration range regardless of ecotype, but no growth occurred at 10.0
      mg Se kg-1. There were no signs of chlorosis or necrosis, and the photosynthetic
      machinery was not affected as evidenced by no marked differences in the structure
      of thylakoid membranes. There was no change in the maximum quantum yield of
      photosystem II (Fv/Fm ratio) in the three ecotypes under Se stress, except for a
      significant negative effect in the ESP ecotype in the 5.0 mg Se kg-1 treatment.
      Glutathione peroxidase (GPx) activity increased as the Se concentration increased
      in the growth medium. GPx activity was higher in the shoot system than the root
      system in all Se treatments. All ecotypes showed great capacity of take up,
      translocate and accumulate selenium in their stem and leaf. Relative Se
      accumulation is best described as leaf ?? stem ? root. The ESP ecotype
      accumulated 1783 MUg g-1 in leaf, followed by BL with 1769 MUg g-1, and STM with
      1606 MUg g-1 in the 5.0 mg Se kg-1 treatment. All ecotypes showed high values of
      translocation and bioaccumulation factors, particularly the ESP ecotype (10.1 and
      689, respectively, at the highest tolerated Se supplementation level). Based on
      these findings, Arundo donax has been identified as the first monocot
      hyperaccumulator of selenium, because Se concentration in the leaves of all three
      ecotypes, and also in the stem of the ESP ecotype, is higher than 0.1% (dry
      weight basis) under the conditions tested. Tolerance up to 5.0 mg Se kg-1 and the
      Se hyperaccumulation capacity make giant reed a promising tool for Se
      phytoremediation.

PMID- 30196462
TI  - Effects of waste lime and Chinese medicinal herbal residue amendments on
      physical, chemical, and microbial properties during green waste composting.
AB  - Traditional composting is time-consuming and often results in a low-quality
      product. The objective of this study was to determine the effects of waste lime
      (WL; at 0, 2.5, and 3.5%) and/or Chinese medicinal herbal residues (CMHRs; at 0,
      10, and 20%) as amendments on the two-stage composting of green waste (GW). The
      combination of WL and CMHRs improved compost particle-size distribution and pH,
      decreased nitrogen loss, and increased cation exchange capacity (CEC), nutrient
      content, and microbial numbers. The combination of WL and CMHRs also accelerated
      organic matter humification and lignocellulose degradation and therefore
      increased the germination index of the final compost. Relative to the non-amended
      compost, the optimal amendment (2.5% WL and 20% CMHRs) increased the percentage
      of particles of ideal size from 23.8 to 66.9%, the pH from 6.69 to 7.17, the CEC
      from 52 to 169 cmol/kg, the humic acid to fulvic acid ratio from 1.32 to 2.49,
      the hemicellulose degradation rate from 42 to 87%, and the cellulose degradation
      rate from 20 to 61%. The treatment with addition of 2.5% WL and 20% CMHRs to GW
      required only 21 days to generate the highest quality compost product.

PMID- 30196463
TI  - Influence of phosphate amendment and zinc foliar application on heavy metal
      accumulation in wheat and on soil extractability impacted by a lead smelter near
      Jiyuan, China.
AB  - Higher concentrations of Pb and Cd in wheat grains harvested in several lead
      smelting-polluted areas in northern China have been reported. This field
      experiment was conducted to investigate the effect of phosphate amendment and Zn
      foliar application on the accumulation of Pb and Cd in wheat grains grown in a
      lead-smelting impacted area in Jiyuan in northern China. The soil (total Pb and
      Cd are 261 and 2.65 mg kg-1, respectively) was amended with superphosphate at
      P:Pb ratios (mol:mol) of 1.90 or 2.57 either during wheat (Triticum aestivum L.)
      planting or a split of 60% of the phosphate applied at planting, with remaining
      40% applied at the jointing stage. Zn was sprayed on the canopy of the wheat
      plants at the jointing stage. The phosphate amendment resulted in lower DTPA
      (diethylene triamine pentaacetic acid)-extractable Pb (1.39-10.7% lower than the
      control) and Cd (0.040-7.12%) in the soil. No significant effect of split
      application of phosphate was found on Pb and Cd availability in soil; however,
      higher rates of P resulted in lower Pb and Cd availabilities in the soil. Grain
      Pb (5.41-21.5% lower than the control), Cd (3.62-6.76%), and Zn (4.29-9.02%)
      concentrations were negatively affected by the phosphate application, with higher
      rates of phosphate resulting in lower grain heavy metal concentrations. Foliar
      application had no statistically significant influence on Pb and Cd
      concentrations in the grain (p > 0.05). Although Pb and Cd concentrations in
      wheat grains were reduced by the phosphate application, their concentrations were
      still much higher than the maximum permissible concentrations for wheat in the
      national standards of China. The results suggest that it is feasible to reduce
      wheat grain concentrations of Pb and Cd in Pb-smelting-polluted areas in northern
      China by soil application of superphosphate; however, the split application of
      the phosphate and the foliar application of Zn compounds do not have substantial
      impact on reducing accumulation of Pb and Cd in the wheat grains.

PMID- 30196461
TI  - Advances of magnetic nanoparticles in environmental application: environmental
      remediation and (bio)sensors as case studies.
AB  - Nanotechnology is an emerging technique drawing increasing attentions in
      biomedical, electronic, environmental, and industrial application. Nanoparticles
      (NPs) possess unique optical, electrical, catalytic, and thermal properties,
      among which magnetic NPs (MNPs) are one of the most important groups with
      excellent superparamagnetism property, large surface area, and biocompatibility.
      In this review, methods for synthesizing and functionalizing MNPs are summarized
      and linked to their applications in environmental science as either adsorbents or
      catalysts for removing contaminants from environmental matrices, illustrating
      stronger reactivity, higher removal capacity, and fast kinetics. Additionally, we
      also comprehensively discuss the application of MNPs as (bio)sensors to
      selectively and sensitively detect the presence of environmental contaminants or
      pathogenic bacteria. This work summarizes the recent progresses of using MNPs as
      powerful tools in environmental science and engineering, raising their state-of
      art application from environmental perspectives and benefiting researchers
      interested in NPs and environmental studies.

PMID- 30196464
TI  - Improved waste-sourced biocomposite for simultaneous removal of crude oil and
      heavy metals from synthetic and real oilfield-produced water.
AB  - Oil- and gas-produced water (PW) which contains various pollutants is an enormous
      threat to the environment. In this study, a novel low-cost bio-adsorbent was
      prepared from shrimp shell and acid-activated montmorillonite. The results of FT
      IR spectroscopy, energy dispersive X-ray (EDX) analysis, and SEM-EDX technique
      indicated that the chitosan-activated montmorillonite (CTS-A-MMT) was prepared
      successfully. The synthesized CTS-A-MMT was applied to remove simultaneously five
      cationic and anionic metal species and crude oil from synthetic and real oilfield
      PW. The adsorption data indicated that crude oil and all studied metals (except
      As) were adsorbed to CTS-A-MMT in a monolayer model (best fitted by Langmuir
      model), while As adsorption fits well with Freundlich model. Kinetic models'
      evaluation demonstrated that the adsorption kinetics of metals on CTS-A-MMT are
      initially controlled by the chemical reaction (film diffusion) followed by intra
      particle diffusion. Application of the prepared CTS-A-MMT in real oilfield PW
      indicated removal efficiency of 65 to 93% for metals and 87% for crude oil in
      simultaneous removal experiments. Presence of additional ions in PW decreased the
      removal of studied metals and crude oil considerably; however, the concentration
      of the investigated pollutants in treated PW is less than the ocean discharge
      criteria. It is concluded that the prepared CTS-A-MMT composite is a low-cost and
      effective adsorbent for treating wastewater contaminated with crude oil and heavy
      metals (i.e., PW).

PMID- 30196465
TI  - Effects of coal blending in electrostatic precipitation efficiency-Inner
      Mongolia, China.
AB  - Based on this study, the Al2O3 content of Jungar coal ash is over 45%, and the
      resistivity of high-Al2O3 ash in Jungar reaches up to 1012 Omega.cm. These
      results seriously influenced the electric characteristics of fly ash, and the
      collection efficiency of electrostatic precipitators (ESPs) evidently decreased.
      To facilitate the effective collection of fine particle in the flue gas generated
      before and after coal blending via ESP, the fly ash obtained from a power plant
      electrostatic precipitation was analyzed in terms of resistivity, size
      distribution, and cohesive force through a portable dust electrical resistivity
      test instrument, Bahco centrifuge, and a cohesive force test apparatus invented
      by the researchers. The mixed ratio of else coal is higher than 50%, the
      resistivity of the fly ash in the flue gas was lowered to approximately two
      orders of magnitude, and the size distribution showed an evident decrease in the
      PM2.5 and PM10 content in fly ash. In addition, the adhesive force and efficiency
      increase from 95.9 to 99.5% in the electrostatic precipitation. Therefore, the
      combustion of blending coal is an effective approach to improve the efficiency of
      ESP used to collect high-Al2O3 fly ash.

PMID- 30196466
TI  - Physicochemical properties of acid- and pepsin-soluble collagens from the
      cartilage of Siberian sturgeon.
AB  - To look for the collagen alternatives of mammalian cartilages from aquatics and
      their by-products, acid-soluble collagen (ASC-SC) and pepsin-soluble collagen
      (PSC-SC) were extracted from cartilages of Siberian sturgeon (Acipenser baerii)
      with yields of 27.13 +/- 1.15 and 14.69 +/- 0.85% on dry weight basis. ASC-SC and
      PSC-SC had glycine as the major amino acid with the contents of 326.8 and 327.5
      residues 1000 residues-1, and their contents of proline and hydroxyproline were
      205.9 and 208.0 residues 1000 residues-1. ASC-SC and PSC-SC comprised type I
      collagen ([alpha1(I)]2alpha2(I)) and type II collagen ([alpha1(II)]3) on the
      literatures and results of amino acid composition, SDS-PAGE pattern, UV, and FTIR
      spectra. Meanwhile, FTIR spectra data indicated that there were more hydrogen
      bonds in ASC-SC and more intermolecular crosslinks in PSC-SC. The maximum
      transition temperature (Tmax) of the ASC (28.3  degrees C) and PSC (30.5  degrees
      C) was lower than those of collagens from mammalian cartilages (> 37  degrees C).
      ASC-SC and PSC-SC showed high solubility in the acidic pH ranges and the
      solubility decreased in the presence of NaCl at concentrations above 3%. Zeta
      potential studies indicated that both ASC-SC and PSC-SC exhibited a net zero
      charge at pH 6.30 and 6.32. SEM results indicated that ASC-SC and PSC-SC
      presented irregular dense sheet-like film linked by random-coiled filaments.
      Therefore, collagens from Siberian sturgeon cartilages might be the suitable
      alternatives of the collagens of mammal cartilages as functional ingredient to
      treat some diseases.

PMID- 30196467
TI  - Hazelnut-enriched chocolate improves flow-mediated artery dilatation via
      inhibition of oxidative stress.

PMID- 30196468
TI  - Antinociceptive action of Achillea biebersteinii methanolic flower extract is
      mediated by interaction with cholinergic receptor in mouse pain models.
AB  - Achillea biebersteinii is a perennial aromatic herb that grows in the
      Mediterranean area. The leaves of this plant are used in foods as bittering and
      appetizing agents. In folk medicine, it is used for the treatment of stomachache
      and abdominal pain. In this study, the analgesic effect of A. biebersteinii
      methanolic flower extract was tested in three pain models, namely: writhing, tail
      flick and paw-licking (formalin) tests. A. biebersteinii extract inhibited
      abdominal cramps produced by acetic acid. The effect of A. biebersteinii was
      better than that of 70 mg/kg indomethacin. In tail flick, A. biebersteinii
      extract increased latency at 30 min and was as effective as 100 mg/kg diclofenac
      sodium. In formalin test, A. biebersteinii extracts decreased paw-licking and
      flinching response in early and late phases. Atropine blocked the action of A.
      biebersteinii extract (300 mg/kg) in the late phase of formalin test as well as
      in writhing and tail-flick tests. GC-MS analysis revealed that ascaridole and iso
      ascaridole were the main constituents of A. biebersteinii flower extract. In
      conclusion, this study shows for the first time that the antinociceptive effect
      of A. biebersteinii is mediated by the cholinergic receptor.

PMID- 30196469
TI  - Infective endocarditis due to Streptococcus dysgalactiae: clinical presentation
      and microbiological features.
AB  - Knowledge of infective endocarditis (IE) caused by Streptococcus dysgalactiae
      (SD) is limited. This study aimed to identify the clinical and microbiological
      features of SD-caused IE and to investigate any possible synergy between
      penicillin and gentamicin on SD isolates. Cases of IE 2008-2016 due to SD
      reported to the Swedish Registry of Infective Endocarditis (SRIE) were
      identified. Isolates were emm typed and synergy between antibiotics was
      determined in time-kill experiments. Medical records were reviewed and SD-cases
      were compared to cases of IE due to other pathogens reported to the SRIE. Fifty
      cases of SD-caused IE were confirmed. emm types stC74a, stG62647, and stG643 were
      most commonly encountered. The patients had a median age of 74 years (range 38
      93) and were significantly older compared to patients with Staphylococcus aureus
      caused IE, (65 years (p = 0.003)). The median time to diagnosis from symptom
      onset was 1 day for patients with SD-caused IE which was less compared to
      patients with IE due to the other pathogens (2-15 days). Embolization was seen in
      46% and the in-hospital mortality was 8%. Etest-based methods did not indicate
      any synergy between penicillin and gentamicin whereas synergy was noted for four
      out of nine isolates applying time-kill assays. This is the largest study of SD
      caused IE, a condition with an acute onset predominantly affecting elderly
      people. Synergy between penicillin and gentamicin against some SD isolates was
      distinguished but the potential benefit of this must be weighed against the risk
      of aminoglycoside side effects.

PMID- 30196470
TI  - Mathematical arterialisation of peripheral venous blood gas for obtainment of
      arterial blood gas values: a methodological validation study in the clinical
      setting.
AB  - Arterial blood gas (ABG) analysis is an essential tool in the clinical assessment
      of acutely ill patients. Venous to arterial conversion (v-TAC), a mathematical
      method, has been developed recently to convert peripheral venous blood gas (VBG)
      values to arterialized VBG (aVBG) values. The aim of this study was to test the
      validity of aVBG compared to ABG in an emergency department (ED) setting. Twenty
      ED patients were included in this study. ABG and three aVBG samples were
      collected from each patient. The aVBG samples were processed in three different
      ways to investigate appropriate sample handling. All VBG samples were
      arterialized using the v-TAC method. ABG and aVBG samples were compared using
      Lin's concordance correlation coefficient (CCC), Bland-Altman plots and
      misclassification analysis. Clinical acceptable threshold of aVBG value deviance
      from ABG values were +/- 0.05 pH units, +/- 0.88 kPa pCO2 and +/- 0.88 kPa pO2.
      CCC revealed an agreement in pH and pCO2 parameters for both aVBG in comparison
      to ABG. In all aVBG samples, an overestimation of pO2 compared to ABG was
      observed. Bland-Altman plot revealed clinically acceptable mean difference and
      limits-of-agreement intervals between ABG and aVBG pH and pCO2, but not between
      ABG and aVBG pO2. Arterialization of VBG using v-TAC is a valid method for
      measuring pH and pCO2, but not for pO2. Larger clinical studies are required to
      evaluate the applicability of v-TAC in different patient subpopulations.

PMID- 30196471
TI  - Early Caregiver-Child Interaction and Children's Development: Lessons from the
      St. Petersburg-USA Orphanage Intervention Research Project.
AB  - We review a series of interrelated studies on the development of children
      residing in institutions (i.e., orphanages) in the Russian Federation or placed
      with families in the USA and the Russian Federation. These studies rely on a
      single population, and many potential parameters that typically vary in the
      literature are similar across studies. The conceptual focus is on the role of
      early caregiver-child interactions and environmental factors that influence those
      interactions in children's development. Generally, children residing in
      institutions that provided minimal caregiver-child interactions displayed delayed
      physical, cognitive, and social-emotional development. Children and adolescents
      adopted from such institutions at 18 months of age or older had higher rates of
      behavioral and executive function problems, even many years after adoption. An
      intervention that improved the institutional environment by increasing the
      quality of caregiver-child interactions-without changes in nutrition, medical
      care, sanitation, and safety-led to substantial increases in the physical,
      cognitive, and social-emotional development of resident children with and without
      disabilities. Follow-up studies of children in this intervention who were
      subsequently placed with USA and Russian families revealed some longer-term
      benefits of the intervention. Implications are discussed for theoretical
      understanding of the role of early caregiver-child interactions in development as
      well as for practice and policy.

PMID- 30196473
TI  - Manipulation of Non-canonical NF-kappaB Signaling by Non-oncogenic Viruses.
AB  - Nuclear factor (NF)-kappaB is a major regulator of antiviral response. Viral
      pathogens exploit NF-kappaB activation pathways to avoid cellular mechanisms that
      eliminate the infection. Canonical (classical) NF-kappaB signaling, which
      regulates innate immune response, cell survival and inflammation, is often
      manipulated by viral pathogens that can counteract antiviral response. Oncogenic
      viruses can modulate not only canonical, but also non-canonical (alternative) NF
      kappaB activation pathways. The non-canonical NF-kappaB signaling is responsible
      for adaptive immunity and plays a role in lymphoid organogenesis, B cell
      development, as well as bone metabolism. Thus, non-canonical NF-kappaB activation
      has been linked to lymphoid malignancies. However, some data strongly suggest
      that the non-canonical NF-kappaB activation pathway may also function in innate
      immunity and is modulated by certain non-oncogenic viruses. Collectively, these
      findings show the importance of studying the impact of different groups of viral
      pathogens on alternative NF-kappaB activation. This mini-review focuses on the
      influence of non-oncogenic viruses on the components of non-canonical NF-kappaB
      signaling.

PMID- 30196472
TI  - TLR2 Expression on Leukemic B Cells from Patients with Chronic Lymphocytic
      Leukemia.
AB  - Antigenic stimulation is considered as a possible trigger of neoplastic
      transformation in chronic lymphocytic leukemia (CLL). B-cell receptor plays a key
      role in the interactions between the microenvironment and leukemic cells;
      however, an important role has also been attributed to Toll-like receptors
      (TLRs). It is believed that disorders of TLR expression may play a part in the
      pathogenesis of CLL. In this study, we investigated the potential role of TLR2 in
      CLL by analyzing its expression on leukemic B cells in correlation with clinical
      and laboratory parameters characterizing disease activity and patients' immune
      status. We assessed the frequencies of TLR2+/CD19+ cells by the flow cytometry
      method in peripheral blood of 119 patients with CLL. The percentage of
      TLR2+/CD19+ cells was significantly lower in patients with CLL as compared to the
      healthy volunteers. There was also a lower percentage of TLR2+/CD19+ cells in CLL
      patients with poor prognostic factors, such as ZAP70 and/or CD38 expression, 17p
      and/or 11q deletion. On the other hand, among patients with del(13q14) associated
      with favorable prognosis, the percentage of TLR2+/CD19+ cells was higher than
      among those with del(11q22) and/or del(17p13) as well as in the control group. We
      found an association between low percentage of CD19+/CD5+/TLR2+ cells and shorter
      time to treatment. We also demonstrated the relationship between low percentage
      of CD19+/CD5+ TLR2-positive and overall survival (OS) of CLL patients. CLL
      patients with a proportion of 1.6% TLR2-positive B CD5+ cells (according to the
      receiver operating characteristic curve analysis) or more had a longer time to
      treatment and longer OS than the group with a lower percentage of TLR2 positive
      cells. To sum up, the results of the study suggest that low TLR2 expression is
      associated with poor prognosis in CLL patients. The monitoring of
      CD19+/CD5+/TLR2+ cells number may provide useful information on disease activity.
      Level of TLR2 expression on leukemic B cells may be an important factor of
      immunological dysfunction for patients with CLL. Our study suggests that TLR2
      could becomes potential biological markers for the clinical outcome in patients
      with CLL.

PMID- 30196474
TI  - Morbidity associated with closure of ileostomy after a three-stage ileal pouch
      anal anastomosis.
AB  - The aim of the study was to compare the perioperative outcomes of patients
      undergoing ileostomy closure after a three-stage ileal pouch-anal anastomosis to
      a control group of patients who had elective colorectal resections and stoma, and
      to analyse the differences based on the technique of closure. The cases were
      retrospectively compared for demographic characteristics and postoperative
      outcomes. Chi-square, Fisher's exact and Wilcoxon rank sum tests were used as
      appropriate. Between 2011 and 2016, 338 patients having their stoma reversed
      after three-stage IPAA were compared to 158 patients in the control group. A
      younger age (43.2 vs 60.6 years, p < 0.0001), a lower body mass index (22 vs 24.4
      kg/m2, p < 0.0001), a higher rate of hand-sewn anastomosis (84.3 vs 15.7%, p <
      0.0001), a lower rate of intraoperative complications (0 vs 1.2%, p = 0.038), a
      shorter operative time (91.5 vs 99.4 min, p = 0.0046) and length of hospital stay
      (6.6 vs 7.6 days, p = 0.045) were seen in the IPAA group. The 30-day rate of
      wound infection, anastomotic leak (0.6 vs 0.6%), small bowel obstruction (SBO, 8
      vs 11.4%) and reoperation (1.8 vs 1.3%) was similar. Among IPAA patients, the
      hand-sewn anastomosis was correlated with a higher chance of developing SBO (9.1
      vs 1.9%, p = 0.03). Closure of ileostomy after three-stage IPAA is associated
      with low rate of serious complications, despite the higher number of previous
      abdominal surgeries. This supports the construction of routine ileostomy during
      IPAA to reduce the risk of pelvic sepsis.

PMID- 30196475
TI  - Muscle transcriptome resource for growth, lipid metabolism and immune system in
      Hilsa shad, Tenualosa ilisha.
AB  - The information on the genes involved in muscle growth, lipid metabolism and
      immune systems would help to understand the mechanisms during the spawning
      migration in Hilsa shad, which in turn would be useful in its future
      domestication process. The primary objective of this study was to generate the
      transcriptome profile of its muscle through RNA seq. The total RNA was isolated
      and library was prepared from muscle tissue of Tenualosa ilisha, which was
      collected from Padma River at Farakka, India. The prepared library was then
      sequenced by Illumina HiSeq platform, HiSeq 2000, using paired-end strategy. A
      total of 8.68 GB of pair-end reads of muscle transcriptome was generated, and
      43,384,267 pair-end reads were assembled into 3,04,233 contigs, of which 23.99%
      of assembled contigs has length >= 150 bp. The total GO terms were categorised
      into cellular component, molecular function and biological process through
      PANTHER database. Fifty-three genes related to muscle growth were identified and
      genes in different pathways were: 75 in PI3/AKT, 46 in mTOR, 76 in MAPK
      signalling, 24 in Janus kinase-signal transducer and activator of transcription,
      45 in AMPK and 27 in cGMP pathways. This study also mined the genes involved in
      lipid metabolism, in which glycerophospholipid metabolism contained highest
      number of genes (32) and four were found to be involved in fatty acid
      biosynthesis. There were 58 immune related genes found, in which 31 were under
      innate and 27 under adaptive immunity. The present study included a large genomic
      resource of T. ilisha muscle generated through RNAseq, which revealed the
      essential dataset for our understanding of regulatory processes, specifically
      during the seasonal spawning migration. As Hilsa is a slow growing fish, the
      genes identified for muscle growth provided the basic information to study
      myogenesis. In addition, genes identified for lipid metabolism and immune system
      would provide resources for lipid synthesis and understanding of Hilsa defense
      mechanisms, respectively.

PMID- 30196476
TI  - Generation of an Rtel1-CreERT2 knock-in mouse model for lineage tracing RTEL1+
      stem cells during development.
AB  - Regulator of telomere length 1 (RTEL1) DNA helicase has been demonstrated to be
      essential for the maintenance of telomeres and genomic stability. This function
      of RTEL1 could be required for protecting stem cells from genomic mutations as
      suggested by its selective expression in stem cell-zones, as well as by RTEL1
      mutations identified in Hoyeraal-Hreidarsson syndrome, a severe dyskeratosis
      congenita that targets primarily stem cell compartments. As a first step to
      establish a role of RTEL1 in stem cells, we generated an Rtel1CreERT2 mouse
      allele in which a tamoxifen-inducible Cre (CreERT2) cDNA was specifically knocked
      into the Rtel1 genomic locus and controlled by the endogenous Rtel1 regulatory
      elements. By crossing with a Cre-dependent LacZ reporter mouse strain (R26RLacZ),
      we further demonstrated that Cre activity in Rtel1CreERT2 mice could be
      specifically induced by tamoxifen, which allowed the fate of RTEL1+ cells to be
      traced at various stages of development. Using this tracing assay, we showed for
      the first time that RTEL1+ cells in the intestine and the testis can act as stem
      cells that have the capacity to self-renew and differentiate into progeny cells.
      Therefore, the Rtel1CreERT2 mice generated in this study will be a valuable
      transgenic tool to explore the function of RTEL1 in stem cells.

PMID- 30196477
TI  - Concomitant subcutaneous intravascular lymphoma lesions in a patient with cardiac
      diffuse large B-cell lymphoma: is intravascular lymphoma a distinct clinical
      entity?
AB  - We describe a patient who presented with large cardiac diffuse large B-cell
      lymphoma (DLBCL) and adrenal masses. The patient also had subcutaneous
      intravascular lymphoma lesions which were detected by random skin biopsy.
      Although ambiguous, minimal extravascular location of lymphoma cells is permitted
      for the diagnosis of intravascular large B-cell lymphoma (IVLBCL) in the WHO
      definition, a number of rare cases have been reported as having concomitant
      tumours in other organs, such as the adrenal gland, brain, and penis. We assume
      that IVLBCL might be a peculiar feature of DLBCL characterised by preferential
      localisation of lymphoma cells within the capillaries rather than a distinct
      disease entity of DLBCL.

PMID- 30196478
TI  - Papillary Thyroid Microcarcinoma: Reclassification to Non-Invasive Follicular
      Thyroid Neoplasm with Papillary-Like Nuclear Features (NIFTP): a Retrospective
      Clinicopathologic Study.
AB  - Papillary thyroid microcarcinoma (PTMC) accounts for nearly 50% of newly
      diagnosed PTC cases. There is considerable debate in literature about the
      clinicopathologic features and prognostic significance of PTMC and whether it
      should be treated as a separate entity. Due to lack of agreement and supportive
      data, the consensus study group that established the criteria for non-invasive
      thyroid neoplasm with papillary-like features (NIFTP) kept its size above 1 cm
      i.e., excluding PTMC from this new group. As a result, to date, some patients
      diagnosed with PTMC get aggressive treatments such as partial or total
      thyroidectomy and even radioactive iodine ablation. We retrospectively studied
      clinicopathologic features and long-term follow-up of 48 cases of papillary
      thyroid microcarcinoma. Of these, 7 cases (15%) had capsular invasion, 2 cases
      (4%) had extrathyroidal extension, 1 case (2%) had lymphovascular invasion, 5
      cases (25%) had lymph node metastases, no case (0%) had any distant metastases,
      and 1 case had recurrence after long-term follow-up (mean 13.7 years, range 1-21
      years). Upon slide review, 8 cases fulfilled the criteria for NIFTP and were sub
      classified under this new category. These 8 cases had no recurrence after long
      term follow-up (mean 12.1 years, range 7-19 years). In this study, we confirmed
      the previous published reports exhibiting indolent nature of PTMC and also
      suggested that PTMC cases that fulfill all the criteria for NIFTP can be sub
      classified under this term in order to avoid unnecessary aggressive treatment.

PMID- 30196479
TI  - Dose prescription point in forward intensity-modulated radiotherapy of breast and
      head/neck cancers.
AB  - In the forward intensity-modulated radiotherapy (FIMRT) technique of treatment
      planning, the isocenter cannot fulfill the requirements of the International
      Commission on Radiation Units and Measurements (ICRU) reference point. This study
      aimed to propose dose prescription points to be used in breast and head/neck
      cancer patients treated using the FIMRT technique. Two-hundred patients with
      head/neck (n = 100) and breast (n = 100) cancers were selected. Treatment plans
      involved using the FIMRT technique. The suggested reference points (SRPs) for
      dose prescription were placed at selected locations in the lateral neck site and
      the tangential site in breast and head/neck cancer patients, respectively. Next,
      doses at the SRPs (DSRPs) were compared to the planning treatment volume (PTV)
      equivalent uniform dose (EUD) and mean dose in the PTV (Dmean) extracted from
      dose-volume histograms. The differences between DSRPs and Dmean for the PTVs were
      less than 2% in 78 cases and less than 1% in 28 cases. The DSRPs were comparable
      with the EUD in both types of PTVs; moreover, paired t test analyses indicated
      that the SRP doses and PTV EUD were statistically similar (p > 0.05). In 116
      cases, the discrepancy between DSRP and EUD was less than 2% and less than 1% in
      74 cases. The SRPs satisfy the ICRU requirement that the reference point dose
      should be clinically relevant and representative of the dose throughout the PTV.
      A consensus on the definition of the reference point is expected to lead to
      accurate inter-comparison between results from different treatment centers,
      facilitating the optimization of treatment procedures.

PMID- 30196480
TI  - Characteristics and risk factors of recurrent keratoconus over the long term
      after penetrating keratoplasty.
AB  - PURPOSE: To determine the characteristics and risk factors of recurrent
      keratoconus (KC) after penetrating keratoplasty (PK). METHODS: We enrolled
      patients who had maintained clear grafts for at least 10 years after PK based on
      their medical records. Patients were divided into the KC group or Others group
      based on the primary indication for PK. Each case was reviewed for clinically
      observed corneal ectasia. Steepest keratometric power (Ks), cylinder (CYL), and
      difference between Ks and minimum keratometric power (MinK) were analyzed in
      patients that underwent corneal topography more than three times after the 5th
      postoperative year. RESULTS: One hundred one eyes of 82 patients were enrolled.
      The KC group comprised 50 eyes and the Others group comprised 51 eyes (herpes [n
      = 22], corneal leukoma [n = 12], and other [n = 17]). The mean period after PK
      was 27.2 years in the KC group and 26.0 years in the Others group. Recurrent KCs
      were observed in 18 eyes of 14 patients (36%), all of whom were in the KC group
      (p = 0.0001). Six of these eyes underwent PK again and all the grafts showed
      keratoconic changes histopathologically. The mean Ks during the whole observation
      period was 52.5 diopters (D) in the KC group and 49.2 D in the Others group (p <
      0.0001). Logistic regression analysis revealed the risk factors of recurrent KC
      with positive Ks change and large CYL with significant p values (p = 0.0102,
      0.0318, respectively). CONCLUSIONS: KC progresses even after PK over the long
      term, requiring re-grafting in some cases. Risk factors for recurrent KC after PK
      are increasing Ks over time and a large CYL.

PMID- 30196481
TI  - Binocular and accommodative function in the controlled randomized clinical trial
      MiSight(r) Assessment Study Spain (MASS).
AB  - PURPOSE: To evaluate the binocular and accommodative function in children wearing
      dual focus (DF) MiSight(r) contact lenses (CLs) for myopia control compared with
      children wearing single-vision (SV) spectacles. METHODS: This was a randomized,
      controlled clinical trial involving subjects aged 8 to 12, with myopia ranging
      from - 0.75 to - 4.00D and astigmatism < 1.00D, allocated to MiSight(r) study CLs
      group or control group wearing SV. Binocular and accommodative function was
      determined at baseline, 12-, and 24-month visits, assessed by the following
      sequence of tests: distance and near horizontal phoria, accommodative
      convergence/accommodation (AC/A) ratio, stereopsis, accommodative amplitude (AA),
      and accommodative response (AR) at 33, 25 and 20 cm. RESULTS: Seventy-four
      children completed the study: 41 in the CL group and 33 in the SV group. CLs
      group did not show any significant differences in binocular and accommodative
      measurements throughout the study. In control group, distance and near phoria,
      stereopsis, AC/A and AR at 20 cm did not show any significant change, but AA, AR
      at 33 cm and AR at 25 cm were greater at 24-month visit compared with baseline (p
      < 0.05). CONCLUSIONS: DF lenses do not change the binocular and accommodative
      function in children wearing dual focus CLs. TRIAL REGISTRATION: NCT01917110.

PMID- 30196482
TI  - Using Acer platanoides annual rings to monitor the amount of heavy metals
      accumulated in air.
AB  - Annual rings are good indicators for determining the increase in the amount of
      heavy metals in the atmosphere from past to the present. Air pollution has
      rapidly increased in Ankara over the past 20 years. In particular, there is a
      serious increase in the concentration of heavy metals that adversely affect human
      health. In this study, the accumulation of Al, Zn, Cu, Co, Fe, Mn, Cr, Cd, Na,
      Ca, Ba, P, Mg, As, and B on Acer platanoides rings has been determined using the
      GBC Integra XL-SDS-270 ICP-OES instrument. Based on our experimental findings, we
      determined that the concentration of heavy metals accumulated on the rings over
      the past 20 years varied and that there was a significant correlation between
      heavy metal concentration in air and heavy metal accumulation on trees. The main
      reasons for this increase were an increase in the amount of exhaust emission
      gases and most importantly the transport of heavy metals by the prevailing winds
      from heavy industrial plants established after 1990 in Ankara. As a result, when
      the values were examined, we found that except for Na, all the elements, which
      showed differences at statistically significant levels, were in considerably high
      quantities in the bark. On average, the values obtained for bark were 6 times
      higher than those obtained for wood. In terms of elements that showed
      statistically significant level of differences, this difference was the lowest in
      P (1.61 times higher), Mg (2.52 times higher), and B (3.94 times higher) and the
      highest in Mn (23.87 times higher), Al (22.0 times higher), and Fe (14.27 times
      higher). In the case of Na, we found that the value obtained for wood was 1.64
      times higher than that obtained for bark.

PMID- 30196483
TI  - Morphometric analysis of talus and calcaneus.
AB  - PURPOSE: The variations in the subtalar joint regarding its morphology and
      articulation of bones are common worldwide. This study aimed to analyze the
      morphometric variations in articulating facets of talus and calcaneum in South
      Indian population. METHODS: For this study, the morphometric parameters of 92 dry
      tali and 49 dry calcanei of unknown gender were analyzed. The pattern of
      articulating facets was classified based on Boyan et al. as Type A (A1-A4), Type
      B (B1 and B2), and Type C. RESULTS: Type B was found to be the most common
      pattern in the study population (talus-97.8%; calcaneus-80.2%). The morphometric
      parameters were expressed as mean +/- 2 SD. The anteroposterior length of the
      left talus was more than right talus, while the transverse width of right and
      left talus is almost equal. The length of right sulcus tali appears to be more
      than left sulcus tali, whereas the width and depth of right and left sulcus tali
      was almost equal. The transverse width of the right calcaneus was greater than
      left calcaneus. Width and depth of right and left sulcus calcanei were almost
      equal, but the length of right sulcus calcanei was more than the left sulcus
      calcanei (p value - 0.036). CONCLUSION: Analysis of the pattern of articulating
      facets of talus and calcaneum and establishing the common types and their
      morphometric parameters will be helpful as an important tool for reconstruction
      surgeries of hind-foot deformities and foot rehabilitation procedures.

PMID- 30196484
TI  - The use of intra-articular analgesics to improve outcomes after temporomandibular
      joint arthrocentesis: a review.
AB  - PURPOSE: The aim of this review was to assess the efficacy of intra-articular
      analgesics in improving outcomes after temporomandibular joint (TMJ)
      arthrocentesis. MATERIAL AND METHODS: An electronic search of PubMed, Scopus, and
      Google scholar databases was performed for papers in English published up to
      December 2017 reporting the use of intra-articular analgesics after TMJ
      arthrocentesis. Randomized controlled trials (RCTs), controlled clinical trials
      (CCTs), comparative studies, retrospective studies, and case series were included
      while case reports, technical reports, animal studies, cadaveric studies, and
      review papers were excluded. RESULTS: Of the six studies included in the review,
      three were RCTs, two were randomized comparative studies, and one was a
      retrospective study. Both opioids and non-steroidal anti-inflammatory drugs have
      been used after TMJ arthrocentesis. Morphine, tramadol, fentanyl, buprenorphine,
      tenoxicam, and COX-2 inhibitors are the drugs used till date. Placebo-controlled
      studies reported improved outcomes after TMJ arthrocentesis with morphine and
      fentanyl but no such results with buprenorphine and tenoxicam. Tramadol was found
      to be better than COX-2 inhibitor. The quality of literature was not high.
      CONCLUSIONS: There is inconclusive evidence in literature on the benefits of
      using intra-articular analgesics after TMJ arthrocentesis. Well-designed high
      quality RCTs with standard protocol studying the effects of intra-articular
      opioids and NSAIDS after TMJ arthrocentesis would provide stronger evidence on
      its use.

PMID- 30196485
TI  - Muraqaba as a Mindfulness-Based Therapy in Islamic Psychotherapy.
AB  - This article first describes Sufism, the mystical/spiritual tradition of Islam
      then move to define Islamic psychotherapy and the various aspects of muraqaba by
      providing an overview of the Sufi literature. I will also highlight how the
      techniques used in muraqaba can be adapted and used as mindfulness-based stress
      reduction, mindfulness-based cognitive therapy, meditation, transcendental
      meditation, mind-body techniques (meditation, relaxation), and body-mind
      techniques. Although muraqaba might not be effective for all mental health
      issues, I suggest a possible value of muraqaba for treating symptomatic anxiety,
      depression, and pain. Furthermore, Muslim clinicians must be properly trained in
      classical Sufi traditions before using muraqaba techniques in their clinical
      practice.

PMID- 30196486
TI  - Boric Acid Activation of eIF2alpha and Nrf2 Is PERK Dependent: a Mechanism that
      Explains How Boron Prevents DNA Damage and Enhances Antioxidant Status.
AB  - Boron is abundant in vegetables, nuts, legumes, and fruit and intake is
      associated with reduced risk of cancer and DNA damage and increased antioxidant
      status. Blood boric acid (BA) levels are approximately 10 MUM BA in men at the
      mean US boron intake. Treatment of DU-145 human prostate cancer cells with 10 MUM
      BA stimulates phosphorylation of elongation initiation factor 2alpha (eIF2alpha)
      at Ser51 leading to activation of the eIF2alpha/ATF4 pathway which activates the
      DNA damage-inducible protein GADD34. In the present study, we used MEF WT and MEF
      PERK (+/-) cells to test the hypothesis that BA-activated eIF2alpha
      phosphorylation requires protein kinase RNA-like endoplasmic reticulum kinase
      (PERK) and activates Nrf2 and the antioxidant response element (ARE). BA (10 MUM)
      increased phosphorylation of eIF2alpha Ser51 in MEF WT cells at 1 h, but not in
      MEF Perk -/- cells exposed for as long as 6 h. GCN2 kinase-dependent
      phosphorylation of eIF2alpha Ser51 was activated in MEF PERK -/- cells by amino
      acid starvation. Nrf2 phosphorylation is PERK dependent and when activated is
      translocated from the cytoplasm to the nucleus where it acts as a transcription
      factor for ARE. DU-145 cells were treated with 10 MUM BA and Nrf2 measured by
      immunofluorescence. Cytoplasmic Nrf2 was translocated to the nucleus at 1.5-2 h
      in DU-145 and MEF WT cells, but not MEF PERK -/- cells. Real-time PCR was used to
      measure mRNA levels of three ARE genes (HMOX-1, NQO1, and GCLC). Treatment with
      10 MUM BA increased the mRNA levels of all three genes at 1-4 h in DU-145 cells
      and HMOX1 and GCLC in MEF WT cells. These results extend the known boric acid
      signaling pathway to ARE-regulated genes. The BA signaling pathway can be
      expressed using the schematic [BA + cADPR -> cADPR-BA -> [[ER]i Ca2+?] -> 3
      pathways: PERK/eIF2alphaP -> pathways ATF4 and Nrf2; and [[ER]i Ca2+?] -> ER
      stress -> ATF6 pathway. This signaling pathway provides a framework that links
      many of the molecular changes that underpin the biological effects of boron
      intake.

PMID- 30196487
TI  - Effect of Injectable Copper and Zinc Supplementation on Weight, Hematological
      Parameters, and Immune Response in Pre-weaning Beef Calves.
AB  - Copper (Cu) and zinc (Zn) deficiency may cause poor weight gain, hematological
      changes, and immune failure in extensive beef cattle breeding systems. Diagnosis
      of the deficiency is based on plasma Cu and Zn concentrations; however, there are
      discrepancies regarding data interpretation. Here, plasma Cu and Zn
      concentrations are discussed as risk markers. We evaluated the effect of
      parenteral Cu and Zn supplementation on their plasma concentrations, weight gain,
      hematological parameters, and antibody titers to bovine herpes virus 1 (BoHV-1).
      Pre-weaning calves (n = 40; 99 +/- 8 kg bw) from a typical breeding area of
      Argentina with background Cu and Zn deficiency were used. They were assigned to
      two homogeneous groups in a completely randomized design. Calves were
      subcutaneously injected with 0.3 mg/kg Cu and 1 mg/kg Zn (supplemented group), or
      saline solution (control), every 40 days during 120 days. Plasma Cu and Zn
      concentrations, hematological parameters, and weight were recorded. On days 40
      and 80 of the trial, calves were vaccinated with inactivated BoHV-1. Antibody
      immune response was measured on days 80 and 120. Data were analyzed with a mixed
      model for repeated measures over time. Before treatment, plasma Cu was low and Zn
      was adequate in both groups. After treatment, plasma Cu increased and remained
      within a normal range, whereas plasma Zn remained constant. Supplemented animals
      had higher weight gain (p < 0.01); higher hematocrit, mean corpuscular volume,
      and mean corpuscular hemoglobin levels (p < 0.05); and higher immune response to
      BoHV-1 (p < 0.05). Our results suggest that Cu and Zn supplementation improved
      daily weight gain and the immune response of pre-weaning calves.

PMID- 30196488
TI  - Chlorogenic Acid Ameliorates Lead-Induced Renal Damage in Mice.
AB  - Lead (Pb) exposure is a global environmental problem and its exposure can lead to
      serious renal damage by disturbing the pro-oxidant/antioxidant balance and
      facilitating inflammation. Chlorogenic acid (CGA) is one of the most abundant
      polyphenols in the diet and has been reported to have many biological properties
      such as antioxidant and anti-inflammatory. In this study, we aimed to investigate
      the protective efficacy and mechanism of CGA against Pb-induced nephrotoxicity in
      mice. The results showed that CGA inhibited Pb-induced bodyweight loss, reduced
      kidney coefficients, and alleviated renal function and structure. Exploration on
      the potential mechanism demonstrated that CGA suppressed Pb-induced inflammation
      in the kidney by regulating NF-kappaB pathway activation. Furthermore, CGA
      significantly increased Pb-induced reduction in the activity of SOD and GSH-Px,
      and reduced Pb-induced increase in the content of MDA. The expression of Bax and
      Bcl-2 associated with apoptosis was also significantly regulated by CGA. These
      data indicated that CGA may play a potential treatment strategy for Pb toxicity.

PMID- 30196489
TI  - Antibody Design and Humanization via In Silico Modeling.
AB  - Antibody humanization process converts any nonhuman antibody sequence into
      humanized antibodies. This can be achieved using different methods of antibody
      design and engineering. This chapter will primarily focus on antibody design
      using a homology model followed by framework shuffling of murine to human
      germline sequence for humanization. Historically, mouse antibodies have been
      humanized using sequence-based approaches, in which all the murine frameworks are
      replaced with most homologous human germline sequence or related scaffold. Most
      often this humanized antibody design, when tested, has a significantly reduced
      binding or no binding to the cognate antigen. This is due to noncompatibility of
      mouse CDRs being supported by non-native human framework scaffold. This mismatch
      between mouse, human structural fold, and elimination of key conformational
      residues often leads to antibody humanization failures. Recently, there has been
      advent of homology modelor structure-guided antibody humanization. Instead of
      humanization based on linear sequence, this approach takes into account the
      tertiary structure and fold of the mouse antibody. A mouse homology model of the
      fragment variable is created, and based on sequence alignment with human
      germline, residues that are different in mouse are replaced with humanized
      sequence in the model. Energy minimization is applied to this humanized model
      that also delineates residues which might have steric clashes due to change in
      the overall tertiary conformation of the humanized antibody. Therefore, a
      homology model-guided with rational mutations, and reintroduction of key
      conformational residues from mouse antibody not only eliminates steric clashes
      but might also restore function in relation to binding affinity to its antigen.

PMID- 30196490
TI  - Antibody Affinity Maturation by Computational Design.
AB  - The immune systems protect our bodies from foreign molecules or antigens, where
      antibodies play important roles. Antibodies evolve over time upon antigen
      encounter by somatically mutating their genome sequences. The end result is a
      series of antibodies that display higher affinities and specificities to specific
      antigens. This process is called affinity maturation. Recent improvements in
      computer hardware and modeling algorithms now enable the rational design of
      protein structures and functions, and several works on computer-aided antibody
      design have been published. In this chapter, we briefly describe computational
      methods for antibody affinity maturation, focusing on methods for sampling
      antibody conformations and for scoring designed antibody variants. We also
      discuss lessons learned from the successful computer-aided design of antibodies.

PMID- 30196491
TI  - Use of IMGT(r) Databases and Tools for Antibody Engineering and Humanization.
AB  - IMGT(r), the international ImMunoGeneTics information system(r) (
      http://www.imgt.org ), was created in 1989 by Marie-Paule Lefranc (Universite de
      Montpellier and CNRS) to manage the huge diversity of the antigen receptors,
      immunoglobulins (IG) or antibodies, and T cell receptors (TR). The founding of
      IMGT(r) marked the advent of immunoinformatics, which emerged at the interface
      between immunogenetics and bioinformatics. Standardized sequence and structure
      analysis of antibody using IMGT(r) databases and tools allow one to bridge, for
      the first time, the gap between antibody sequences and three-dimensional (3D)
      structures. This is achieved through the IMGT Scientific chart rules, based on
      the IMGT-ONTOLOGY concepts of classification (IMGT gene and allele nomenclature),
      description (IMGT standardized labels), and numerotation (IMGT unique numbering
      and IMGT Collier de Perles). IMGT(r) is acknowledged as the global reference for
      immunogenetics and immunoinformatics, and its standards are particularly useful
      for antibody engineering and humanization. IMGT(r) databases for antibody
      nucleotide sequences and genes include IMGT/LIGM-DB and IMGT/GENE-DB,
      respectively, and nucleotide sequence analysis is performed by the IMGT/V-QUEST
      and IMGT/JunctionAnalysis tools and for NGS by IMGT/HighV-QUEST. In this chapter,
      we focus on IMGT(r) databases and tools for amino acid sequences, two-dimensional
      (2D) and three-dimensional (3D) structures: the IMGT/DomainGapAlign and IMGT
      Collier de Perles tools and the IMGT/2Dstructure-DB and IMGT/3Dstructure-DB
      database. IMGT/mAb-DB provides the query interface for monoclonal antibodies
      (mAb), fusion proteins for immune applications (FPIA), and composite proteins for
      clinical applications (CPCA) and related proteins of interest (RPI) and links to
      the proposed and recommended lists of the World Health Organization International
      Nonproprietary Name (WHO INN) programme, to IMGT/2Dstructure-DB for amino acid
      sequences, and to IMGT/3Dstructure-DB and its associated tools
      (IMGT/StructuralQuery, IMGT/DomainSuperimpose) for crystallized antibodies.

PMID- 30196492
TI  - Construction of Human Naive Antibody Gene Libraries.
AB  - Size and variability often represent an obstacle in generating an effective
      antibody gene library for the detection of an abundant repertoire of antigens.
      Therefore, optimizing the construction of a large library is essential for the
      selection of high-affinity reactive fragments. Here, we report a highly efficient
      method for the construction of a human naive antibody gene library for the
      selection of antibodies as single-chain variable fragments. This protocol is
      based on many different sets of oligonucleotide primers and multistep
      electroporation and ligation reactions.This advanced method can be adopted by any
      molecular biology laboratory to generate a naive library for use in isolating
      single-chain fragment variables against specific targets.

PMID- 30196493
TI  - Construction of Synthetic Antibody Libraries.
AB  - Libraries of antibody fragments displayed on filamentous phages are now a widely
      used approach to isolate antibodies against virtually any target. We describe a
      simple protocol to make large and diverse libraries based on a single or a
      limited number of frameworks. The approach is flexible enough to be used with any
      antibody format, either single-chain (scFv, VHH) or multi-chain (Fv, Fab,
      (Fab')2), and to target in a single step the six complementarity-determining
      regions-or any other part-of the antibody molecule. Using this protocol,
      libraries larger than 1010 can be constructed in a single week.

PMID- 30196494
TI  - Construction of Histidine-Enriched Shark IgNAR Variable Domain Antibody Libraries
      for the Isolation of pH-Sensitive vNAR Fragments.
AB  - The adaptive immune system of sharks comprises a heavy chain-only antibody
      isotype, referred to as immunoglobulin new antigen receptor (IgNAR). Antigen
      binding in case of IgNAR antibodies is mediated by a single variable domain
      (vNAR). Due to their inherent beneficial biophysical properties, such as small
      size and high thermal stability combined with a high specificity and affinity to
      their target antigens, vNAR domains emerged as promising tools for
      biotechnological and biomedical applications. Herein, we present detailed
      protocols for the engineering of pH-sensitivity into IgNAR V domains by
      constructing histidine-enriched and CDR3-diversified semisynthetic antibody
      libraries which can then be screened upon using yeast surface display.
      Protonation or deprotonation of incorporated histidine residues at different pH
      values results in structural transitions caused by altered electrostatic
      interactions. These interactions account for an altered binding behavior toward
      the target antigen. In the following protocol, we describe the generation of a
      semisynthetic vNAR master library that comprises two histidine residues on
      average in the 12-residue CDR3 loop. Moreover, once a pH-dependent vNAR
      population toward the target antigen is identified, this population can further
      be optimized in terms of affinity and pH sensitivity upon conducting a CDR1
      mediated affinity maturation.

PMID- 30196495
TI  - Display Technologies for Generation of Ig Single Variable Domains.
AB  - Variable fragments of heavy-chain-only antibodies (VHH) found in camelids are
      valuable research tools in pharmacology and biotechnology and are being developed
      for the clinic to treat patients with autoimmune and infectious diseases or
      cancer. Their single-domain nature and biochemical properties greatly facilitate
      the development process. The most common technology to select single-domain
      antibody fragments is phage display following active immunization of llamas or
      other members of Camelidae family. Selection of VHH from immune phage libraries
      is a rapid approach to discover a broad panel of in vivo matured antigen-specific
      clones with comprehensive functionalities. In this chapter, we describe a
      detailed protocol for construction of VHH immune libraries and phage display
      selection against antigens in their native conformation.

PMID- 30196496
TI  - A Streamlined Approach for the Construction of Large Yeast Surface Display Fab
      Antibody Libraries.
AB  - Yeast surface display is a versatile platform technology for antibody discovery.
      Nevertheless, the construction of antibody Fab libraries typically is a tedious
      multistep process that involves the generation of heavy chain as well as light
      chain display plasmids in different haploid yeast strains followed by yeast
      mating. Here, we present a focused one-step Golden Gate cloning approach for the
      generation of yeast surface display Fab libraries that allows for simultaneous
      introduction of heavy-chain and light-chain variable regions into one single
      display vector. Thereby, the overall time as well as the materials needed for
      library generation can be reduced significantly.

PMID- 30196497
TI  - Phage Display and Selections on Purified Antigens.
AB  - The isolation of antibody fragments targeting proteins implicated in cancers and
      other diseases remains a crucial issue on targeted therapy or diagnostic tool
      development. In many case, the protein of interest, or a relevant portion of this
      protein such as its extracellular domain, is available as purified protein. In
      such cases, phage display on purified antigen is an easy and fast way to select
      antibody fragment able to efficiently bind this antigen. However the output of
      phage selection can vary significantly depending on the way to immobilize the
      purified antigen during selection. The following protocols describe the selection
      of phage antibody on purified antigen adsorbed on plastic, i.e., panning, or a
      selection in solution, using a biotinylated antigen as well as the corresponding
      screening produces, and give hints on the advantage and drawbacks of each
      approach.

PMID- 30196498
TI  - Selection of Antibodies to Transiently Expressed Membrane Proteins Using Phage
      Display.
AB  - Cell membrane proteins serve as attractive targets for biopharmaceutical
      development in addition to gauging their fundamental process in a biological
      system. Approximately 38% of the entire genome codes for plasma membrane
      proteins; however the discovery and development of antibody binders to such
      targets are a technical challenge. Methods to raise binders against such targets
      by cloning and expressing soluble extracellular regions have been met with
      limited success due to the loss of critical epitopes, with the resulting
      antibodies failing to bind to their target in its native conformation. This
      chapter outlines a "cell based biopanning" method in order to isolate antibodies
      against membrane proteins in their native conformation using transiently
      expressed, GFP-tagged target proteins. This method overcomes the limitations of
      non-specific binding of phage to the cells, abundance of irrelevant antigens on
      the cell surface, while retaining the native structure of the antigen on the cell
      surface.

PMID- 30196499
TI  - Selection of Antibody Fragments Against Structured DNA by Phage Display.
AB  - In addition to the canonical B-form structure, DNA can adopt alternative
      conformations including Z DNA, triplex DNA, as well as G4 and i-Motif quadruplex
      structures. Such structures have been shown to form in cells in a dynamic manner.
      Monoclonal antibodies against such structures represent key tools to study the
      biological functions of these structures. Here we provide protocols for the
      generation of antibody fragments against structured DNA using phage display
      selections.

PMID- 30196500
TI  - Selection of Antibody Fragments by Yeast Display.
AB  - The critical need for renewable, high-quality affinity reagents in biological
      research, as well as for diagnostic and therapeutic applications, has required
      the development of new platforms of discovery. Yeast display is one of the main
      methods of in vitro display technology with phage display. Yeast display has been
      chosen by numerous groups to refine both affinity and specificity of antibodies
      because it enables fine discrimination between mutant clones of similar affinity.
      In addition, the construction of display libraries of antibody fragments in yeast
      permits to sample the immune antibody repertoire more fully than using phage.
      This chapter gives an updated overview of the available systems of yeast display
      platforms and libraries, followed up by technical descriptions of selection
      methods of antibody fragments by yeast display.

PMID- 30196501
TI  - Rapid Selection of High-Affinity Antibody scFv Fragments Using Ribosome Display.
AB  - Ribosome display has proven to be a powerful in vitro selection and evolution
      method for generating high-affinity binders from libraries of folded proteins. It
      works entirely in vitro, and this has two important consequences. First, since no
      transformation of any cells is required, libraries with much greater diversity
      can be handled than with most other techniques. Second, since a library does not
      have to be cloned and transformed, it is very convenient to introduce random
      errors in the library by PCR-based methods and select improved binders. Thus, a
      true directed evolution, an iteration between randomization and selection over
      several generations, can be conveniently carried out, e.g., for affinity
      maturation, either on a given clone or on the whole library. Ribosome display has
      been successfully applied to antibody single-chain Fv fragments (scFv), which can
      be selected not only for specificity but also for stability and catalytic
      activity. High-affinity binders with new target specificity can be obtained from
      highly diverse libraries in only a few selection rounds. In this protocol, the
      selection from the library and the process of affinity maturation and off-rate
      selection are explained in detail.

PMID- 30196502
TI  - In Vitro Selection of Single-Domain Antibody (VHH) Using cDNA Display.
AB  - Single-domain antibody (e.g., Nanobody, VHH antibody) is a promising scaffold for
      therapeutic and diagnostic reagents. To expand the range of target molecules, in
      vitro selection using cell-free display technologies such as cDNA display is
      useful and powerful because of their huge libraries and robust stability. We
      provide technical details for in vitro selection of single-domain antibodies
      using cDNA display.

PMID- 30196503
TI  - Sequencing and Affinity Determination of Antigen-Specific B Lymphocytes from
      Peripheral Blood.
AB  - Here we describe methods for screening human blood to isolate peripheral blood
      mononuclear cells (PBMCs) capable of binding fluorescently labeled antigen, as
      well as methods for the amplification and sequencing of B cell receptor (BCR)
      heavy and light chain genes. Detailed protocols are provided for transient
      mammalian expression in a hexahistidine-tagged Fab format, purification by
      immobilized metal affinity chromatography (IMAC), and affinity determination by
      BioLayer interferometry (BLI).

PMID- 30196504
TI  - Expression of IgG Monoclonals with Engineered Immune Effector Functions.
AB  - The therapeutic development of monoclonal antibodies requires robust and reliable
      methods for their recombinant expression and characterization. In this context,
      an increasingly important aspect in the antibody development process is to
      determine the contribution of Fc-mediated immune effector functions to
      therapeutic activity. Here we describe steps for the cloning and mammalian
      expression of mouse and human IgG monoclonals with reduced immune effector
      functions, based on mutation of Fc-gamma receptor and complement-binding sites.
      The resulting antibody preparations contain low levels of endotoxin and are
      suitable for testing in animal models of disease.

PMID- 30196505
TI  - An IRES-Mediated Tricistronic Vector for Efficient Generation of Stable, High
      Level Monoclonal Antibody Producing CHO DG44 Cell Lines.
AB  - The generation of stable, high-level monoclonal antibody (mAb) producing cell
      lines remains a major challenge in biopharmaceutical industry. The commonly used
      plasmid vectors for mAb expression, which express light chain (LC), heavy chain
      (HC), and selection marker genes on separate vectors or via multiple promoters on
      a single vector, are not able to accurately control the ratio of LC over HC
      expression and tend to result in non-expressing clones. To overcome these issues,
      we have developed a tricistronic vector using two internal ribosome entry sites
      (IRES) to express the LC, HC, and dihydrofolate reductase (DHFR) selection marker
      genes in one transcript. In this tricistronic vector, the three genes are under
      the control of a hapten-modified human cytomegalovirus (hCMV) promoter containing
      a core CpG island element (IE) to enhance the production stability. The LC gene
      is arranged as the first cistron followed by a wild-type IRES to control the HC
      expression. Such design expresses excess LC polypeptides which enhance mAb
      expression level and reduce aggregate. A mutated IRES with attenuated strength is
      applied on DHFR to reduce its expression for enhancing the stringency of
      selection for high producers. This vector allows easy generation of stable, high
      mAb producing CHO DG44 pools and clones for antibody development and
      manufacturing.

PMID- 30196506
TI  - Production, Purification, and Characterization of Antibody-TNF Superfamily Ligand
      Fusion Proteins.
AB  - Antibody-fusion proteins with ligands, e.g., of the TNF superfamily (TNFSF) can
      be adequately produced in mammalian expression systems. Here, we describe the
      transient production in adherent and suspension human embryonic kidney cells at
      laboratory scale, followed by purification procedures applying protein A and
      immobilized metal affinity chromatography for proteins with Fc domain and 6 *
      histidine-tag, respectively. In addition, characterization of the purified
      proteins by size exclusion chromatography is described.

PMID- 30196507
TI  - Chemoenzymatic Defucosylation of Therapeutic Antibodies for Enhanced Effector
      Functions Using Bacterial alpha-Fucosidases.
AB  - Core fucosylation plays a critical role in modulating the effector functions of
      therapeutic antibodies such as the antibody-dependent cellular cytotoxicity
      (ADCC) through adversely affecting the affinity of antibodies for Fcgamma
      receptors. Thus, a facile method for Fc defucosylation of antibodies is important
      both for functional studies and for an enhanced therapeutic efficacy. In this
      chapter, we describe a detailed protocol for chemoenzymatic defucosylation of
      antibodies using Herceptin (trastuzumab) as a model system. The protocol includes
      (a) Fc deglycosylation using endoglycosidase S2 (Endo-S2); (b) enzymatic
      defucosylation of the resulting Fucalpha1,6GlcNAc-Herceptin using two distinct
      bacterial alpha-fucosidases, AlfC and BfFuc; (c) transglycosylation of the GlcNAc
      Herceptin using an Endo-S2 mutant (Endo-S2 D184M) as the enzyme and a complex N
      glycan oxazoline as the donor substrate; and (d) SPR analysis of the binding of
      antibody glycoforms with the FcgammaIIIA receptor. The protocol of enzymatic
      defucosylation of Herceptin should be equally applicable for the Fc glycan
      engineering of other mAbs.

PMID- 30196508
TI  - Fc Glyco- and Fc Protein-Engineering: Design of Antibody Variants with Improved
      ADCC and CDC Activity.
AB  - Monoclonal antibodies are established treatment options in cancer therapy.
      However, not all patients benefit from antibody therapy. Basic research and
      findings from clinical trials revealed that certain Fc-mediated effector
      mechanisms triggered by monoclonal antibodies are essential for efficient
      antitumor activity. Today, next-generation monoclonal antibodies can be designed
      displaying tailor-made improved effector functions. The introduction of Fc
      engineering technologies offers the potential to fine-tune Fc-mediated effector
      functions such as antibody-dependent cell-mediated cytotoxicity (ADCC),
      phagocytosis, or complement-dependent cytotoxicity (CDC). Fc-engineered
      antibodies hopefully will overcome some limitations of current forms of antibody
      therapy.

PMID- 30196509
TI  - Fc Engineering: Tailored Synthetic Human IgG1-Fc Repertoire for High-Affinity
      Interaction with FcRn at pH 6.0.
AB  - The therapeutic efficacy of an antibody drug depends on the variable domains and
      on the constant crystallizable fragment (Fc). IgG variable domains have been the
      targets of extensive molecular engineering in search of more specific binders
      with higher affinities for their targets. Similarly, Fc engineering approaches
      have led to modulating both the immune effector responses and serum half-lives of
      therapeutic antibodies. A high-affinity interaction between the IgG Fc and
      neonatal Fc receptor (FcRn) at a slightly acidic pH can protect IgG molecules
      from undergoing lysosomal or serum proteinase-induced degradation. Here we
      describe an optimized protocol for the development of a tailored, synthetic human
      Fc repertoire to select Fc mutants which show highly pH-restricted FcRn binding
      with high affinity.

PMID- 30196510
TI  - Measuring Antibody-Antigen Binding Kinetics Using Surface Plasmon Resonance.
AB  - Surface plasmon resonance (SPR) is now widely embraced as a technology for
      monitoring a diverse range of protein-protein interactions and is considered
      almost de rigueur for characterizing antibody-antigen interactions. The technique
      obviates the need to label either of the interacting species, and the binding
      event is visualized in real time. Thus, it is ideally suited for screening crude,
      unpurified antibody samples that dominate early candidate panels following
      antibody selection campaigns. SPR returns not only concentration and affinity
      data but when used correctly can resolve the discrete component kinetic
      parameters (association and dissociation rate constants) of the affinity
      interaction. Herein, we outline some SPR-based generic antibody screening
      configurations and methodologies in the context of expediting data-rich ranking
      of candidate antibody panels and ensuring that antibodies with the optimal
      kinetic binding characteristics are reliably identified.

PMID- 30196511
TI  - Parallel Evolution of Antibody Affinity and Thermal Stability for Optimal
      Biotherapeutic Development.
AB  - Naive antibody libraries provide a rich resource for the identification of
      binding domains against targets of therapeutic interest. Being naive in nature
      means a lack in antigen bias, resulting in a breadth of diversity with respect to
      epitopes that can be successfully targeted. In combination with display-based
      technology platforms, selection strategies allow for the generation of ortholog
      cross-reactive binding domains which enable critical preclinical proof-of-concept
      studies. However, naive binding domains often suffer from low target affinity. In
      addition, construction of large naive libraries results in non-native pairing of
      heavy and light v-domains which can present a challenge to molecular stability.
      Here we describe effective methods for the parallel evolution of antibody
      affinity and thermal stability which couple mutant antibody library phage display
      with carefully designed selection strategies.

PMID- 30196512
TI  - The Use of Somatic Hypermutation for the Affinity Maturation of Therapeutic
      Antibodies.
AB  - The engineering of antibodies and antibody fragments for affinity maturation,
      stability, and other biophysical characteristics is a common aspect of
      therapeutic development. Maturation of antibodies in B cells during the adaptive
      immune response is the result of a process called somatic hypermutation (SHM), in
      which the activation-induced cytidine deaminase (AID) acts to introduce mutations
      into immunoglobulin (Ig) genes. Iterative selection and clonal expansion of B
      cells containing affinity-enhancing mutations drive an increase in the overall
      affinity of antibodies. Here we describe the use of SHM coupled with mammalian
      cell surface display for the maturation of antibodies in vitro and the
      complementarity of these methods with the mining of immune lineages using next
      generation sequencing (NGS).

PMID- 30196513
TI  - Selection and Use of Intracellular Antibodies.
AB  - Intracellularly expressed recombinant antibodies, or intrabodies, are powerful
      tools for cell biology studies as well as therapeutic applications. Cell
      biologists use them to either block the intracellular antibody target or to image
      endogenous target dynamics. We describe here methods to select recombinant
      antibodies from antibody phage display libraries and to subsequently express them
      as fluorescent intrabodies.

PMID- 30196514
TI  - Site-Specific Radioactive Labeling of Nanobodies.
AB  - Single-domain antibody fragments, also called nanobodies (Nbs), are increasingly
      being used as targeting molecular tools for imaging and/or targeted radionuclide
      therapy. To translate these tools to the clinic, it is preferred to obtain a
      homogeneous, well-defined, and well-characterized product. It has been shown that
      Sortase A, a transpeptidase found in Staphylococcus aureus, catalyzes the site
      specific conjugation between a recognition oligopeptide (LPXTG, known as sortag)
      and an oligoglycine functionalized probe. This versatile technique manages to
      couple various molecular reagents, such as biotin, fluorophores, bifunctional
      chelators, etc., to the target protein containing the sortag. This chapter
      focuses on the site-specific coupling of a bifunctional chelator (e.g., CHX-A"
      DTPA) to a Nb equipped with a C-terminal sortag. The chelator conjugated to the
      Nb can be radiolabeled with 111In or 177Lu for SPECT imaging or targeted
      radionuclide therapy, respectively.

PMID- 30196515
TI  - Cost evolution of biological agents for the treatment of spondyloarthritis in a
      tertiary hospital: influential factors in price.
AB  - Background Spending on biological agents has risen dramatically due to the high
      cost of the drugs and the increased prevalence of spondyloarthritis. Objective To
      evaluate the annual cost per patient and cost for each biological drug for
      treating patients with spondyloarthritis from 2009 to 2016, and to calculate
      factors that affect treatment cost, such as optimizing therapies by monitoring
      drug serum levels, the use of biosimilar-TNF inhibitors, and official discounts
      or negotiated rebates in biologicals acquired by the pharmacy department. Method
      Retrospective, observational study in a Spanish tertiary hospital. Main outcome
      Annual cost per patient and per drug. Factors that influenced the costs and socio
      demographic parameters and disease activity. Results A total of 129, 215, and 224
      patients were treated in 2009, 2013, and 2016, respectively. The annual cost per
      patient decreased: EUR11,604 in 2009, EUR8513 in 2013, and EUR7464 in 2016. The
      introduction of new drugs drives economic competition, leading to total savings
      per drug, with discounts reaching 5.8, 12.4, 16.7, 17.7, 13.7, and 24.8% for
      original infliximab, etanercept, adalimumab, ertolizumab, golimumab, and
      secukinumab, respectively, while rebates for biosimilar infliximab reached 31.90%
      in 2016. The number of patients with optimized therapies reached 47.5% in 2016,
      which led to cost savings of EUR798,614, in addition to savings from official
      discounts and rebates of EUR252,706 and savings from optimized therapies of
      EUR545,908 in 2016. Conclusion The cost of biological treatments declined after
      official discounts, negotiated rebates, and optimized therapies, leading to a
      significant decrease in the annual cost per patient. The greatest contribution to
      economic savings in biological therapy according to our study was biological
      therapy optimization.

PMID- 30196517
TI  - Psychiatric morbidity in inflammatory bowel disease: Time to screen all the
      patients.

PMID- 30196516
TI  - Psychiatric comorbidities in patients with inflammatory bowel disease.
AB  - BACKGROUND: Psychiatric comorbidities are associated with inflammatory bowel
      disease (IBD). We conducted an observational study to evaluate the prevalence of
      depression and anxiety in patients with IBD. METHODS: Seventy consecutive
      consenting patients with IBD (62 ulcerative colitis [UC], 8 Crohn's disease [CD];
      40 males, mean age [SD] 36.2 [11.3] years) and 100 healthy volunteers (44 males,
      age 31.22 [SD] [10.5] years) as controls were enrolled. All participants were
      directed to take self-assessment tests, Patient Health Questionnaire -9 (PHQ-9)
      and Symptom Checklist Anxiety Scale (SCL-A20). Participants having a score >= 10
      on PHQ-9, or >= 29 on SCL-A20 were administered the Hamilton Depression Rating
      Scale (HAM-D) or Hamilton Anxiety (HAM-A) scales, respectively. The severity of
      depression and anxiety was graded with HAM-D and HAM-A scales, respectively. The
      protocol was approved by the Institutional Ethics Committee. RESULTS: The
      prevalence of depression (34.3% vs. 5%, p < 0.0001, OR 9.7) and anxiety (18.6%
      vs. 2%, p = 0.0002, OR 11.17) was higher in patients with IBD as compared to
      controls. The severity of depression was higher in patients compared to controls
      (mean rank 17 vs. 7, p = 0.04). The prevalence of depression was not different
      between UC and CD; all IBD patients with anxiety had UC. The mean duration of
      disease and history of corticosteroid treatment or surgery for IBD were not
      associated with the presence of depression or anxiety. Patients with severe CD
      (Crohn's disease activity index, CDAI > 450) had more severe depression. The
      severity of UC did not correlate with severity of anxiety or depression in UC.
      CONCLUSIONS: Anxiety and depression are more prevalent in IBD patients as
      compared to healthy individuals.

PMID- 30196519
TI  - A Modified Surgical Technique to Treat Strabismus in Complete Sixth Nerve Palsy.
AB  - INTRODUCTION: A lot of different techniques have been proposed in order to manage
      abduction limitation secondary to sixth nerve palsy; however, anterior segment
      ischemia remains a concern. The aim of this study was to evaluate the results of
      augmented vertical recti muscle transposition (VRT) with partial recession of
      medial rectus muscle (MR) for complete, chronic sixth nerve palsy, a new modified
      technique that could also minimize the risk for anterior segment ischemia (ASI).
      METHODS: In this nonrandomized 8-year (2009-2017) retrospective review, 20
      patients with complete sixth nerve palsy and contracted MR were enrolled. All of
      them underwent augmented VRT and partial recession of the MR, following a new
      proposed surgical technique. Only the central part of the MR tendon and belly was
      recessed by 6.5 mm, leaving 1.5 mm of the upper pole and 1.5 mm of the lower pole
      of the muscle intact, preserving the circulation of two anterior ciliary
      arteries. RESULTS: Twenty patients with a mean age of 43 years (range 12-71), all
      unilateral cases, were enrolled in this study. The mean preoperative deviation
      was 64.25 +/- 10.9 prism diopters (PD) base out (range 50 to 90). In 17 cases
      (88%), the postoperative deviation was within 10 PD of orthotropia. Two patients
      (10%) had residual esotropia (15 PD and 20 PD, respectively), and one patient
      (5%) had 10 PD of hypotropia. The mean preoperative abduction limitation of -5.9
      improved to -3.1 (p < 0.0001). None of the cases presented with ASI (success rate
      100%). CONCLUSION: Partial recession of the MR preserving the two anterior
      ciliary arteries (Kozeis modified technique) with augmented vertical recti muscle
      transposition is an effective procedure, with a high success rate and is probably
      less risky for ASI.

PMID- 30196518
TI  - Role and safety of human thrombin injection for the treatment of bleeding gastric
      varices.
AB  - BACKGROUND: Human thrombin appears to be a new effective tool in the
      armamentarium of management of bleeding gastric varices, but there are paucity of
      data on its use. Thus, we share our experience with human thrombin in the
      treatment of bleeding gastric varices. METHODS: It was a prospective
      interventional study conducted between September 2015 and December 2017. Patients
      with upper gastrointestinal bleeding from gastric varices were included, while
      patients with previous history of cyanoacrylate glue injection or band ligation
      were excluded. RESULTS: A total of 20 patients including 13 males (mean age 32.65
      [18-52] years) presenting with gastric variceal bleeding requiring endoscopic
      injection of human thrombin were studied. The underlying diagnosis was cirrhosis
      in 8 patients, and extrahepatic portal vein thrombosis, noncirrhotic portal
      fibrosis, and chronic pancreatitis in 6, 4, and 2 patients, respectively.
      Isolated gastric varices were found in 6 patients while 14 patients had
      gastroesophageal varices (GOV) (GOV1-3, GOV2-11). Patients received 1 to 3
      sessions (mean = 1.3) of thrombin with a mean total dose of 700 IU (range = 500
      2000 IU). Mean follow up was 16.8 months (range 3-28 months). Hemostasis in the
      acute setting was successfully managed in all the 20 patients on initial
      presentation. On serial follow up, 4 out of 20 patients required repeat
      endoscopic session for gastric varices. No thrombin injection-related
      complication was recorded. CONCLUSION: Endoscopic therapy with thrombin appears
      safe and effective in the management of bleeding gastric varices.

PMID- 30196520
TI  - Biological variation of procalcitonin levels in hemodialysis patients.
AB  - BACKGROUND: There is no obvious evidence regarding biological variation of
      procalcitonin (PCT) levels in hemodialysis (HD) patients without infections. The
      aim of this study was to determine the within- and between-person biological
      variation of PCT levels in HD patients without infections. METHODS: A
      multicenter, prospective, cohort study enrolled 123 HD patients without any signs
      of infectious disease. Baseline PCT levels were determined pre- and post-HD, and
      then repeated pre-HD PCT measurements were performed at 2, 4, 8, 12, 16, 20, and
      24 weeks after baseline blood-sampling, regardless of the presence or absence of
      infectious disease. Analytical variation (CVa), the within-person biological
      variation (CVi), between-person biological variation (CVb), individual index
      (II), and the reference change value (RCV) were calculated. RESULTS: The mean age
      was 62.4 years, 76.4% were male, and 32.5% had diabetes. The mean duration of HD
      was 87 months. The median value for baseline pre-HD PCT was 0.23 ng/mL, which is
      much higher than the reference level for healthy individuals. PCT levels
      decreased of 46.6% after a single HD session. CVi was 24.9%, CVb was 54.2%, II
      was 0.46, and RCV was calculated as 96.4% with 99% probability. CONCLUSIONS: The
      PCT level was significantly higher in stable HD patients without manifest
      bacterial infection. CVb was more variable than CVi in HD patients, which
      indicates that relative change is more important than absolute PCT levels for
      diagnosing bacterial infection, and doubling or more of the baseline PCT level
      may imply the presence of a bacterial infection in HD patients.

PMID- 30196521
TI  - Dental considerations and recommendations in Eisenmenger syndrome: A report of an
      unusual paediatric case.
AB  - BACKGROUND: Eisenmenger syndrome (ES) is a heart cyanotic condition characterised
      by elevated pulmonary vascular resistance and an intra-cardiac right-to-left
      shunting of blood through a systemic-to-pulmonary circulation connection.
      Affected children usually exhibit severe hypoxia, clubbing of fingers/toes,
      haemoptysis, anaemia, and organ damage. CASE REPORT: During autumn 2015, the
      patient and her parents arrived at the paediatric dentistry clinic. The patient
      presented with the main complaint of generalised inflamed gingival tissues,
      severely protruded upper incisors, and evident abnormal mouth breathing.
      TREATMENT: This was performed under local analgesia, rubber-dam isolation, and
      antimicrobial prophylaxis with amoxicillin (50 mg/kg). The patient's parents
      agreed to the treatment plan through a signed informed consent. This treatment
      consisted of the placement of pit and fissure sealants on the four permanent
      first molars (which included enamel preparation with fissurotomy burs), in-depth
      gingiva/dental frequent cleanings, local fluoride varnish applications, and an
      exhaustive programme of at-home oral hygiene (brushing, flossing, and
      chlorhexidine mouth rinses), including adequate nutrition. Gingivoplasty surgery
      to remove residual enlarged tissues was indicated for the near future. FOLLOW-UP:
      The child did not return to the clinic. When contacted, the parents reported that
      their daughter's systemic condition worsened significantly. She was confined to a
      bed at home under palliative care, with a life-span expectation of only a few
      months. CONCLUSION: Comprehensive dental care of children with ES requires
      careful consideration of their medical condition, and dental care delivery should
      be coordinated with the paediatric cardiologist. General analgesia should be
      considered only in strictly selected cases, due to the high peri-operative
      mortality reported.

PMID- 30196522
TI  - Cervical lymphadenopathy: can the histogram analysis of apparent diffusion
      coefficient help to differentiate between lymphoma and squamous cell carcinoma in
      patients with unknown clinical primary tumor?
AB  - PURPOSE: To retrospectively evaluate the value of whole-lesion histogram analysis
      of apparent diffusion coefficient (ADC) maps in differentiating between lymphoma
      and metastatic squamous cell carcinoma (SCC) of unknown clinical primary in neck
      nodes. METHODS: A total of 39 patients, 20 affected by lymphoma and 19 affected
      by metastatic non-nasopharyngeal SCC, were included in this retrospective study.
      All patients underwent MR imaging with a 1.5 T scanner system, including
      diffusion-weighted imaging (DWI) with three different b values (b = 0, 500 and
      800 s/mm2). The entire tumor volume was manually delineated on the ADC maps,
      using the T2-weighted images and DWIs with b = 800 s/mm2 as a guide to the lesion
      location. The Mann-Whitney rank-sum test for independent samples was performed to
      compare the histogram parameters of patients with lymphoma and SCC. RESULTS: The
      SCCs showed significantly higher median ADC (ADCmedian) and mean ADC (ADCmean)
      values, compared to lymphomas (p < 0.001), while they exhibited lower kurtosis
      and skewness without reaching significance (p = 0.066 and 0.148, respectively).
      The ADCmean and ADCmedian had the best discriminative powers for differentiating
      lymphoma and SCC, with an area under the curve of 87% and 85%, respectively. The
      optimal cutoff values for ADCmean and ADCmedian as predictors for lymphoma were
      <= 0.83 * 10-3 mm2/s and <= 0.73 * 10-3 mm2/s, respectively. CONCLUSIONS: The
      whole-lesion ADC histogram analysis of cervical lymphadenopathy may help to
      discriminate lymphomas from non-nasopharyngeal SCC in patients with unknown
      clinical primary tumor.

PMID- 30196524
TI  - Upregulation of HSP60 expression in the postnatal rat cochlea and rats with drug
      induced hearing loss.
AB  - Heat shock protein 60 (HSP60) is a highly conserved chaperone molecule that plays
      important roles in mediating some physiological and pathological functions.
      However, researchers have not yet determined whether HSP60 is expressed in the
      mammalian cochlea. This study constitutes the first investigation of the
      expression of HSP60 in the postnatal rat cochlea. We also examined the expression
      of HSP60 in rats with drug-induced hearing loss. Auditory thresholds were
      assessed by monitoring the auditory brainstem response (ABR) prior to and after
      drug injection. Expression levels of the HSP60 gene (Hsp60) and HSP60 protein in
      the rat cochlea were detected by quantitative real-time polymerase chain reaction
      and Western blotting, respectively. The distribution of HSP60 in the rat cochlea
      was further examined by immunofluorescence staining. We have demonstrated that
      HSP60 was expressed in the postnatal rat cochlea in an age-dependent and cell
      specific manner. In addition, after drug exposure, the average hearing threshold
      of rats in the experimental group was significantly higher than that in the
      control group, with increased HSP60 expression level in response to kanamycin and
      furosemide treatments. HSP60 expression was observed in the supporting cells
      (SCs) within the organ of Corti in both the uninjured and the injured cochlea,
      but it was undetectable in the mechanosensory hair cells (HCs) and spiral
      ganglion neurons. Therefore, our research suggests that HSP60 may play an
      important role in auditory function.

PMID- 30196525
TI  - Gender differences in relations between alcohol-related compensatory behavior and
      eating pathology.
AB  - PURPOSE: Concerns about caloric intake associated with alcohol use (e.g., fear of
      weight gain) are positively associated with compensatory eating behaviors (e.g.,
      caloric restriction, self-induced vomiting), a phenomenon that has been
      identified across gender. Specific motivations for compensatory behaviors differ;
      some relate to eating disorder (ED) pathology (e.g., shape and weight concerns),
      and others to alcohol (e.g., enhancing effects). Research examining motivations
      for alcohol-related compensatory behaviors in men is limited to date. The current
      study sought to assess how specific types of alcohol-related compensatory
      behaviors and their association with ED pathology present differently by gender.
      METHODS: Undergraduates (N = 530, 48% female) completed the Compensatory Eating
      Behaviors in Response to Alcohol Consumption Scale (CEBRACS), Eating Disorders
      Diagnostic Scale (EDDS), and reported height, weight, and frequency and quantity
      of alcohol consumption. Data were examined using linear regression, and relations
      between CEBRACS behaviors and eating pathology were compared across gender.
      RESULTS: Factors that were positively associated with EDDS scores for both men
      and women included alcohol-related dietary restraint, and exercise. For women,
      but not men, alcohol-related bulimic behavior also contributed to elevations in
      EDDS scores. CONCLUSIONS: Findings indicate that specific types of alcohol
      related compensatory eating behaviors (i.e., dietary restraint and exercise) are
      positively related to ED pathology for both male and female participants. In
      contrast, bulimic behaviors' association with ED pathology is gender specific.
      Understanding gender differences in alcohol-related compensatory behaviors and ED
      risk may inform gender-specific intervention targets. LEVEL OF EVIDENCE: Cross
      sectional descriptive study, Level V.

PMID- 30196523
TI  - In silico fragment-mapping method: a new tool for fragment-based/structure-based
      drug discovery.
AB  - Here, we propose an in silico fragment-mapping method as a potential tool for
      fragment-based/structure-based drug discovery (FBDD/SBDD). For this method, we
      created a database named Canonical Subsite-Fragment DataBase (CSFDB) and
      developed a knowledge-based fragment-mapping program, Fsubsite. CSFDB consists of
      various pairs of subsite-fragments derived from X-ray crystal structures of known
      protein-ligand complexes. Using three-dimensional similarity-matching between
      subsites on one protein and another, Fsubsite compares the surface of a target
      protein with all subsites in CSFDB. When a local topography similar to the
      subsite is found on the surface, Fsubsite places a fragment combined with the
      subsite in CSFDB on the target protein. For validation purposes, we applied the
      method to the apo-structure of cyclin-dependent kinase 2 (CDK2) and identified
      four compounds containing three mapped fragments that existed in the list of
      known inhibitors of CDK2. Next, the utility of our fragment-mapping method for
      fragment-growing was examined on the complex structure of tRNA-guanine
      transglycosylase with a small ligand. Fsubsite mapped appropriate fragments on
      the same position as the binding ligand or in the vicinity of the ligand.
      Finally, a 3D-pharmacophore model was constructed from the fragments mapped on
      the apo-structure of heat shock protein 90-alpha (HSP90alpha). Then, 3D
      pharmacophore-based virtual screening was carried out using a commercially
      available compound database. The resultant hit compounds were very similar to a
      known ligand of HSP90alpha. As a result of these findings, this in silico
      fragment-mapping method seems to be a useful tool for computational FBDD and
      SBDD.

PMID- 30196526
TI  - Psychometric evaluation of the English version of the Dusseldorf Orthorexie Scale
      (DOS) and the prevalence of orthorexia nervosa among a U.S. student sample.
AB  - PURPOSE: Recently, the concept of orthorexia nervosa (ON) as a potential new
      variant of disordered eating behavior has gained popularity. However, published
      prevalence rates appear to be questionable given the lack of validity of the
      available questionnaires. The Dusseldorf Orthorexie Scale (DOS) is a validated
      questionnaire only available in German to measure orthorexic behavior. METHODS:
      The DOS was translated into English using the back-translation process.
      Cronbach's alpha was used to establish internal consistency and an intra-class
      correlation coefficient was calculated to assess reliability. The Eating Habits
      Questionnaire (EHQ) was used to test construct validity and the Eating Disorders
      Inventory was used to test discriminant validity. Principal and confirmatory
      factor analyses were carried out to test the factor structure. The sample
      consists of 384 university students in the U.S. RESULTS: English (E)-DOS and EHQ
      were highly correlated (r = 0.76, p < .001) indicating very good construct
      validity. Cronbach's alpha coefficient reached 0.88, indicating very good
      internal consistency. Confirmatory factor analyses revealed a poorly fitted one
      factor model, but good results for the standardized coefficients for the 10 items
      ranging between 0.52 and 0.82 were found. According to the E-DOS, 8.0% of the
      students exceeded the preliminary cut-off score, while an additional 12.4% would
      be considered being at risk of developing ON. CONCLUSIONS: The E-DOS appears to
      be a valid, reliable measure for assessing ON. The results revealed higher
      prevalence rates for orthorexic behavior among U.S. students compared to German
      students. Cultural aspects could play a role in those differences. LEVEL OF
      EVIDENCE: Descriptive study, Level V.

PMID- 30196527
TI  - Structural validation of ORTO-11-ES for the diagnosis of orthorexia nervosa,
      Spanish version.
AB  - PURPOSE: The ORTO-11-ES questionnaire is a tool to assess the pathological
      obsession displayed by some individuals regarding healthy eating. The aims of
      this study were (1) to confirm the factor structure of the Spanish version of
      ORTO-11-ES using confirmatory factor analysis (CFA) and (2) to examine the
      possible association between the ORTO-11-ES score, gender and body mass index
      (BMI). METHODS: The sample comprised 492 students from the University of Castilla
      la Mancha, Spain. Of these, 280 were women (56.9%). Participants were surveyed
      using the ORTO-11-ES questionnaire. RESULTS: The confirmatory factor analysis
      (CFA) supported the 11 elements and 3 domains of this tool as the better fitting
      model; for the Comparative Fit Index (CFI) and the Tucker-Lewis Index (TLI), the
      values were 0.94 and 0.91, respectively, and the Root Mean-Square Error of
      Approximation (RMSEA) was 0.058. The tendency towards orthorexic behavior is more
      associated with the female gender. The BMI had no influence on the tendency for
      ON. CONCLUSIONS: This study is the first attempt to confirm the three-factor
      structure of a Spanish version of the ORTO-15 questionnaire. These findings
      suggest that the ORTO-11-ES may be a valuable tool for identifying subjects with
      specific eating behavior patterns. This information may be useful for health
      professionals involved in the research, development and implementation of
      interventions catered to individuals suffering from this eating disorder. LEVEL
      OF EVIDENCE: Level V, descriptive cross-sectional study.

PMID- 30196528
TI  - The use of enteral nutrition in the treatment of eating disorders: a systematic
      review.
AB  - PURPOSE: Enteral nutrition (EN) is frequently used in the treatment of anorexia
      nervosa (AN), and less commonly, bulimia nervosa (BN); yet, no standardized
      guidelines for treatment exist at this time. The aim of this review is to
      investigate the efficacy of EN in the treatment of eating disorders and make
      recommendations for clinical practice and future research. METHODS: An exhaustive
      literature search of 7 databases was completed. The search strategy combined key
      terms anorexia nervosa, bulimia, and eating disorders with terms associated with
      EN. There were no restrictions on publication date or language. Studies that
      assessed the effect of EN on weight restoration, refeeding syndrome, and
      binge/purge behaviors in the treatment of AN and BN were included. RESULTS: Of 73
      full-text articles reviewed, 22 met inclusion criteria. Nineteen studies reported
      that significant short-term weight gain was achieved when EN was used for
      refeeding malnourished AN patients; however, results varied for the six studies
      reporting on long-term weight gain, maintenance, and recovery. In studies with a
      comparator, no significant differences were found between the EN and oral
      refeeding cohorts regarding gastrointestinal disturbance, refeeding syndrome, or
      electrolyte abnormalities. Five studies examined the effect of EN on binge/purge
      behaviors, suggesting that temporary exclusive EN decreases the frequency and
      severity of binge/purge episodes. CONCLUSION: Although EN is an essential life
      saving treatment in severe cases of AN, it does not guarantee long-term success
      or recovery. The results of this systematic review highlight the need for
      prospective controlled trials with adequate sample sizes to make comparisons
      between specific feeding methods, formulations, and defined short and long-term
      outcomes. Evidence-based standards for clinical practice are needed with specific
      guidelines for best results for AN and BN treatment. LEVEL OF EVIDENCE: I,
      systematic review.

PMID- 30196529
TI  - Determinants of binge eating disorder among normal weight and overweight female
      college students in Korea.
AB  - PURPOSE: The aim of the present study was to describe the clinical features of
      binge eating disorder (BED) in normal weight and overweight undergraduate Korean
      women. METHODS: 117 overweight (BMI >= 25 kg/m2) and 346 normal weight (18 kg/m2
      <= BMI < 25 kg/m2) undergraduate Korean women completed questionnaires to assess
      for BED. Their emotional eating behaviors, binge eating-related behaviors, a
      spectrum of compulsive behaviors such as substance abuse and obsessive-compulsive
      disorder, and psychological profiles were evaluated through personal interviews
      and questionnaires. The features of those with BED were compared to those without
      BED in the overweight and normal weight groups. RESULTS: Both normal weight and
      overweight BED women had higher levels of functional impairment, eating disorder
      psychopathology including emotional and external eating behaviors, and
      neuroticism than their non-BED counterparts. In the normal weight group, BED
      women had more frequent alcohol consumption and obsessive-compulsive symptoms
      than non-BED women. In the overweight group, BED women had higher levels of
      depression and lower extraversion than non-BED women. CONCLUSIONS: BED is
      associated with global functional impairment and mental health problems. Thus,
      the association with high functional impairments and psychiatric comorbidities
      suggest that people with BED may benefit from treatment. LEVEL III: Evidence
      obtained from well-designed case-control analytic studies, from more than one
      center.

PMID- 30196530
TI  - Advancements in imaging technology for microvascular free tissue transfer.
AB  - The use of preoperative imaging has become routine for many reconstructive
      microsurgeons to help localize perforators for planning of microvascular free
      flaps. However, with advancements in imaging technology, perforator mapping
      represents only one potential benefit as virtual planning and medical modeling,
      and flap tissue perfusion are also rapidly becoming commonplace and the standard
      of care for many surgeons who perform high-volume free flap reconstruction for
      the breast, head and neck, torso, and the extremities.

PMID- 30196531
TI  - An evolutionary view of patient experience in primary care: A concept analysis.
AB  - AIM: This concept analysis explores "patient experience" in the context of
      primary care. BACKGROUND: In the 21st century, person-centered care became the
      manner to address the healthcare quality needs of the United States. This study
      led to using measures of patient experience as an evaluation of patient-centered
      care. DESIGN: Concept analysis. DATA SOURCES: CINAHL, Cochrane Review, PUBMED
      Central, PsycINFO, Web of Science, and Scopus were queried using "patient
      experience" and "primary care." All peer-reviewed US-based articles were included
      from January 2000 to October 2017 (n = 59). REVIEW METHODS: Rodgers' evolutionary
      view of concept analysis guided this inquiry. RESULTS: Patient experience is any
      process discernible by patients, including subjective experiences, objective
      experiences, and observations of provider or staff behavior. Patient experience
      reports are mediated and moderated by many variables and reflect care experiences
      that directly measure patient-centeredness from the patient's viewpoint.
      Consequences of patient experience may lead to adherence to shared plans of care,
      patient engagement, and appropriate use of healthcare services. CONCLUSION:
      Conceptual clarity of patient experience adds to the understanding of how
      patients experience healthcare quality. If healthcare aspires to deliver patient
      centered care, understanding quality from the viewpoint of the patient is
      essential.

PMID- 30196532
TI  - Noninvasive detection of cancer spread to lymph nodes: A review of molecular
      imaging principles and protocols.
AB  - Identification of cancer spread to tumor-draining lymph nodes offers critical
      information for guiding treatment in many cancer types. Current clinical methods
      of nodal staging are invasive and can have substantial negative side effects.
      Molecular imaging protocols have long been proposed as a less invasive means of
      nodal staging, having the potential to enable highly sensitive and specific
      evaluations. This review article summarizes the current status and future
      perspectives for molecular targeted nodal staging.

PMID- 30196533
TI  - Sentinel lymph node biopsy in patients with thin melanomas: Frequency and
      predictors of metastasis based on analysis of two large international cohorts.
AB  - BACKGROUND: Sentinel lymph node (SLN) metastasis in patients with thin melanomas
      (<=1 mm) is uncommon but adverse prognostic factors may indicate an increased
      risk. We sought to determine how often SLN biopsy (SLNB) was performed in
      patients with thin melanomas, establish the frequency of SLN metastasis and
      evaluate the predictive value of ulceration, tumor mitotic rate, and thickness
      for SLN involvement. METHODS: Melanoma patients with a Breslow thickness greater
      than or equal to 0.5 to less than or equal to 1 mm, diagnosed 2009-2016, were
      identified in the Swedish Melanoma Register (SMR) and the Melanoma Institute
      Australia (MIA) Database. RESULTS: In total 8165 patients were included from the
      SMR and 1603 from MIA. SLNB was performed in 9.5% and 16.2% of patients,
      respectively. Corresponding figures for T1b (American Joint Committee on Cancer
      [AJCC] 7th Edition) were 19.5% and 24.6%. The SLN positivity rate were 4.4%
      (Sweden) and 5.8% (MIA). SLN metastasis was more frequent in tumors with
      ulceration, mitoses, and Breslow thickness greater than or equal to 0.9 mm but
      none were statistically significant. Younger age was identified as a significant
      risk factor for SLN positivity at MIA. CONCLUSIONS: A minority of patients with
      thin melanomas had SLNB performed and the SLN positivity rate was low. This study
      did not confirm tumor ulceration, mitoses, or thickness as statistically
      significant predictors for SLN metastasis.

PMID- 30196534
TI  - Development and validation of a nomogram for predicting survival in Chinese han
      patients with resected colorectal cancer.
AB  - BACKGROUND: Estimates of survival after curative colorectal cancer (CRC) surgery
      are the basis of patient care and treatment planning. A nomogram is a useful tool
      for individualized cancer prognosis. METHODS: A total of 2450 patients with
      nonmetastatic CRC were included to develop a nomogram. Prognostic factors were
      identified and integrated by the Cox proportional hazards model. Then, we
      developed and validated a prognostic nomogram. The performance of this model was
      assessed by the concordance index (C-index) and a calibration curve. The nomogram
      was internally validated by bootstrapping and externally validated with a
      separate database of 299 patients from The Cancer Genome Atlas. RESULTS: Age, T
      stage, N stage, histological type, tumor location, lymph-vascular invasion,
      preoperative carcinoembryonic antigen, and sample lymph nodes were integrated
      into the nomogram. The C-index of the nomogram for predicting overall survival
      was higher than that of the seventh edition American Joint Committee on Cancer
      TNM staging system (training data set, 0.76 vs 0.68, respectively; P < 0.001;
      validation data set, 0.78 vs 0.69, respectively; P = 0.003). CONCLUSION: We
      developed a prognostic nomogram for patients with nonmetastatic CRC, which could
      provide a more individualized outcome prognostication than that afforded by the
      TNM staging system by using common clinicopathologic factors.

PMID- 30196535
TI  - CD90 expression in human intrahepatic cholangiocarcinoma is associated with lymph
      node metastasis and poor prognosis.
AB  - BACKGROUND AND OBJECTIVES: Intrahepatic cholangiocarcinoma (ICC) is the second
      most common primary liver cancer. However, its prognosis remains poor. Expression
      of cluster of differentiation 90 (CD90) has been identified as an indicator of
      poor prognosis in many cancers. Here, we examined the importance of CD90
      expression in ICC. METHODS: We performed immunohistological assays for CD90 in
      human ICC surgical specimens and assessed its relationship with
      clinicopathological findings and prognosis. Moreover, we analyzed the
      characteristics of CD90+/- cells, mainly with respect to metastatic potential,
      using human ICC cell lines. RESULTS: CD90 expression was significantly associated
      with lymph node metastasis and was revealed to be an independent prognostic
      factor. The CD90+ cells present in ICC specimens did not appear to be cancer
      associated fibroblasts, as they did not express alpha-smooth muscle actin. In
      vitro, CD90 + cells exhibited greater migratory ability and higher expression of
      epithelial-mesenchymal transition (EMT)-related genes, including CXCR4 and MMP7,
      than CD90- cells. Wnt/beta-catenin signaling pathway activation was also
      heightened in CD90+ cells. In such cells, EMT appeared to be induced by CXCR4 and
      MMP7 expression through activation of Wnt/beta-catenin signaling. CONCLUSION:
      CD90+ cells demonstrate high metastatic potential owing to Wnt/beta-catenin
      signaling activation and are associated with poor prognosis in ICC.

PMID- 30196536
TI  - Professional male caregiving: A concept analysis.
AB  - The number of men in professional caregiving roles has increased. While still a
      small percentage, the numbers of men in these roles continues to expand. Too
      often, the methods that professional male caregivers use to provide care differ
      from their female counterparts. There has not been much research conducted to
      understand how males in the professional role differ from their female
      counterparts in terms of caregiving characteristics.

PMID- 30196537
TI  - Readmission after pulmonary resection for lung cancer.

PMID- 30196538
TI  - Predictive value of breast magnetic resonance imaging in detecting
      mammographically occult contralateral breast cancer: Can we target women more
      likely to have contralateral breast cancer?
AB  - BACKGROUND AND OBJECTIVES: Preoperative breast magnetic resonance imaging (B-MRI)
      staging in newly diagnosed breast cancer increases detection of synchronous
      contralateral findings, but may result in false-positive outcomes. This study
      objective was to identify women more likely of having mammographically occult,
      MRI detected contralateral breast cancer (CBC). METHODS: We performed a
      retrospective review of patients who had preoperative B-MRI prior to surgery from
      2010 to 2015 and collected patient imaging and clinicopathologic data.
      Multivariate logistic regression was used to identify predictors of CBC. RESULTS:
      MRI resulted in contralateral findings in 201 of 1894 patients (10.6%). Overall
      3.2% (60 of 1894) had synchronous CBC detected on B-MRI. The majority of CBCs (n
      = 60) were stage 0 or IA (85.0%), hormone receptor positive (94.9%), human
      epidermal growth factor receptor 2 (HER2/neu) negative (89.7%), and
      low/intermediate pathological grade (87.2%). Women more likely to have CBC were
      older (P < .001), had lobular index cancer (P = .03), and estrogen receptor (ER)+
      (P = .027) or progesterone receptor (PR)+ (P = .002) tumors. On multivariate
      analysis (receiver operating characteristic curve area = 0.75), PR + status (P =
      .022), and older age (P = .004) were predictive of CBC. CONCLUSIONS: Preoperative
      MRI is most effective in detecting early stage, hormone receptor-positive CBC in
      older women.

PMID- 30196540
TI  - Fenestrated ASD device "angioplasty": How to adjust a "pop-off" mechanism when
      needed.
AB  - We report on three cases of atrial septal defect (ASD) closure where a handmade
      fenestration had to be modified after device implantation. Two patients suffered
      from left ventricular diastolic dysfunction and one had severe pulmonary arterial
      hypertension. Amplatzer ASD occluder fenestration was created in all patients.
      Devices were implanted using an "over-the-wire" implantation technique. Due to a
      sub-optimal hemodynamic result, fenestration was upsized by using a new
      technique.

PMID- 30196539
TI  - Neutrophil to lymphocyte ratio is an independent predictor of outcome for
      patients undergoing definitive resection for stage IV melanoma.
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was to perform a retrospective
      analysis of survival rates and determine prognostic indicators for patients who
      underwent definitive surgical resection of stage IV melanoma. METHODS: Patients
      included were those who underwent complete resection of metastatic melanoma. Data
      was analyzed using IBM SPSS 2.0. Survival estimates were derived from Kaplan
      Meier, log-rank, and Breslow tests. RESULTS: The study population (n = 95)
      consisted of 60 males and 35 females. Median overall survival (OS) from the first
      metastasectomy was 49 months (95% confidence interval, 31-67 months). OS at 1, 2,
      and 5 years was 92%, 87%, and 50% respectively. Predictors of survival included
      clear surgical margins compared to patients with positive margins (median OS 53
      vs 20 months, P = .026). A preoperative neutrophil to lymphocyte ratio less than
      5 experienced a median OS of 65 months compared to 15 months ( P = .006;
      multivariable analysis for OS: hazard ratio 3.590, P = .009). CONCLUSION: This
      study's results are consistent with previous findings demonstrating favourable
      long-term outcomes following selective resection of metastatic melanoma. In
      addition to achieving clear surgical margins, a low preoperative neutrophil to
      lymphocyte ratio was associated with improved outcomes. These factors may help
      identify surgical candidates.

PMID- 30196541
TI  - Novel approach to coronary artery perforation repair.
AB  - Coronary artery perforation (CAP) during percutaneous coronary intervention is a
      rare but serious complication. Treatment options of CAP include prolonged balloon
      inflation, covered stent, and coil embolization. Although most cases of CAP can
      be treated with prolonged balloon inflation, some cases, especially Ellis grade
      III CAP require covered stents or coiling. Covered stents may require a large
      bore guide catheter and have a high rate of restenosis, which can be a limiting
      factor in patients with severe peripheral arterial disease. Coil embolization is
      generally used in distal CAP because coiling in the proximal vessels results in a
      large territory of infarction. We present a case of an Ellis grade III CAP during
      rotational atherectomy successfully treated with a novel coiling technique
      whereby the thrombogenic coil extends through the perforation outside of the
      vessel, and the intraarterial portion of the coil is excluded from the lumen by
      drug-eluting stent placement over the proximal portion of the coil.

PMID- 30196542
TI  - Use of Amplatzer vascular plugs and Amplatzer duct occluder II additional sizes
      for occlusion of patent ductus arteriosus: A multi-institutional study.
AB  - BACKGROUND: Variable patent ductus arteriosus (PDA) morphology and the need to
      close PDAs in small size patients has led physicians to use Amplatzer Vascular
      Plugs (AVP) and recently available Amplatzer Duct Occluder II - Additional Sizes
      (ADO II AS). The purpose of this study was to analyze the safety, efficacy, and
      complication rates of the ADO II AS and AVPs, specifically AVP II. METHODS: All
      patients undergoing PDA closure with an AVP or ADO II AS from 2011 to 2016 were
      included. Clinical, echocardiographic, and angiographic data were collected and
      reviewed. RESULTS: Four hundred and sixty-nine patients were included. Median age
      was 27 months (0.75-852) and the median weight was 11.4 kg (1-92). There were 51
      patients <=5 kg. Type A PDA was most common in 48% (n = 225), followed by type E
      (27.5%, n = 129), type D (13%, n = 61), type C (10.2%, n = 48), and type B (1.3%,
      n = 6). Devices included AVP II (n = 421), ADO II AS (n = 30), and AVP IV (n =
      18), left pulmonary artery stenosis occurred in 4.3% (n = 20). One patient
      required surgery for severe stenosis; the remaining cases were mild and required
      no intervention. Device embolization occurred in 3 patients (10%) with the ADO II
      AS. Successful device closure was achieved in 98.9% of cases. CONCLUSIONS: The
      AVP II was highly effective for closing PDAs in smaller babies with varying
      morphologies and is safe when used in small sized patients with relatively low
      risk of complications. More studies are warranted to clarify the risks of ADO II
      AS.

PMID- 30196543
TI  - Coronary intervention and arteria lusoria-Not simple as it may seem.
AB  - We reviewed the letter from Dr. Walter W. Woody and would like to thank him for
      showing his interest in our article and providing his opinion and point of view.
      However, we respectfully disagree with few points that have been raised.
      Switching to a femoral approach was considered to be a safer alternative for
      percutaneous intervention due to the presence of arteria lusoria. Risks and
      possible complications would include increased contrast use, increased radiation
      exposure, aortic dissection and even cerebral stroke, all of which have been
      reported extensively in literature. One single procedural methodology cannot be
      applied to a particular clinical scenario, whether simple or challenging. We have
      multiple different catheters and multiple different interventional approaches at
      our disposal to help and guide us through a case, in the best interest of the
      patient.

PMID- 30196544
TI  - Radial first, radial second, and beyond.

PMID- 30196545
TI  - Study of biodegradable occluder of atrial septal defect in a porcine model.
AB  - OBJECTIVE: To evaluate the safety and feasibility of a modified poly(l-lactic
      acid) (PLLA) atrial septal defect (ASD) occluder. METHODS: Forty-five piglets
      were divided into two groups: an experimental group (n = 27) and a control group
      (n = 18). The experimental group underwent percutaneous implantation of a
      modified PLLA ASD device while the control group underwent percutaneous
      implantation of a widely used metal ASD device. X-ray imaging, transthoracic
      echocardiography (TTE), electrocardiogram (ECG), histopathology and electron
      microscopic examination were performed at 7 days, 1, 3, 6, and 12 months after
      implantation. RESULTS: Twenty-seven experimental piglets and 18 control piglets
      were all successfully implanted with modified biodegradable and metal ASD
      devices, respectively. While both devices exhibited very good occluding effects,
      the modified PLLA ASD devices were completely endothelialized at 3 months after
      implantation, and the endothelialization appeared to be more complete compared to
      the control group. Degradation of the PLLA devices was noted at 12 months follow
      up with no loss of integrity at the atrial septum. CONCLUSION: This animal model
      with implanting of the occluders was effective and not associated with
      complications. The modified PLLA ASD devices are more controllable and practical
      than our previous devices. The implanted devices demonstrated good
      endothelialization and degradability in short and moderate term follow-up. Long
      term studies are now underway to further evaluate the biodegradability of this
      novel device.

PMID- 30196546
TI  - Influence of novel X-ray imaging technology on radiation exposure during chronic
      total occlusion procedures.
AB  - OBJECTIVES: We assessed whether use of the novel X-ray imaging technology
      AlluraClarity (Philips Healthcare, Best, The Netherlands) results in a meaningful
      reduction of radiation exposure for patients during coronary intervention on
      chronic total occlusions (CTO-PCI) compared to its predecessor Allura Xper
      (Philips Healthcare, Best, The Netherlands). BACKGROUND: Percutaneous coronary
      intervention on chronic total occlusion causes 2- to 10-fold higher radiation
      burden on patients and operators compared to standard PCI. To avoid iatrogenic
      damage to our patients and personnel, all efficient ways to reduce radiation
      should be identified and implemented. METHODS: Radiation exposure of 196
      consecutive CTO patients treated in the same laboratory by a single experienced
      operator (total experience: > 2,500 CTOs, annual experience: > 100 CTOs/year) was
      analyzed. Ninety-eight CTO-PCIs (n1 ) were performed with the Allura Xper system
      and 98 patients (n2 ) were treated using AlluraClarity. RESULTS: The two groups
      had similar BMI (n1 : mean 28.43 kg/m2 ; n2 : mean 28.41 kg/m2 ), procedure
      duration (n1 : mean 75.9 min; n2 : mean 70.7 min), and J-CTO scores (n1 : mean
      2.99; n2 : mean 2.82). The success rates did not differ (n1 : 86/98 successful).
      n2 : 87/98 successful). The radiation doses, however, revealed significant
      differences in kerma area product (KAP; absolute reduction of 34%; n1 : mean 61.5
      Gycm2 ; n2 : mean 40.8 Gycm2 ; P < 0.002) and cumulative air kerma (AK; absolute
      reduction of 30%; n1 : mean 966.8 mGy; n2 : mean 675.9 mGy; P < 0.002).
      CONCLUSION: Use of the novel X-ray imaging technology resulted in a meaningful
      and significant reduction in patient radiation exposure during complex coronary
      interventions (CTO-PCI) compared to use of its predecessor. Similar success rates
      support the operator's subjective impression of similar, and in some cases
      superior, image quality.

PMID- 30196547
TI  - Premounted stents for branch pulmonary artery stenosis in children: A short term
      solution.
AB  - OBJECTIVE: Define outcomes of premounted stent implantation (PMS) for branch
      pulmonary artery stenosis (BPAS). BACKGROUND: PMS for BPAS in children raises
      concern of long term viability, with limited maximal expansion. METHODS: We
      reviewed our cardiac database over an 11-year period ending in 2013. Primary
      endpoint was need for surgical stent intervention (SSI). Other endpoints included
      acute results and repeat interventions (RI). RESULTS: 82 PMS were implanted in 60
      children for BPAS. Median weight was 6.3 (25th -75th 4.6-9.8) kg. Median stent
      diameter was 6 (range 4-9) mm. Acutely, vessel diameter improved from 2.0 (25th 
      75th 1.6-3.4) to 5.0 (25th -75th 4.2-5.9) mm (p < 0.001), pressure gradient
      decreased from 41 (25th -75th 29-50) to 11 (25th -75th 7-18) mmHg (n = 47, p <
      0.001), RV:Ao pressure ratio decreased from 100% (25th -75th 85-110%) to 59%
      (25th -75th 49-74%) (n = 40, p < 0.001). Freedom from SSI was 81% at 1 year and
      35% at 5 years. Freedom from RI was 50% at 1 year and 14% at 5 years. 86% of PMS
      underwent SSI during a concomitant planned cardiac surgery. 45% patients had
      stent redilation, improving stent diameter from 4.6 (25th -75th 4.1-5.4) to 5.7
      (25th -75th 4.9-7) mm (p < 0.001). 1 stent (3%) was able to be fractured
      longitudinally. CONCLUSIONS: PMS is an effective short term solution for BPAS in
      children. PMS is associated with expected early need for transcatheter
      reintervention to accommodate for growth, but also has high rates of SSI.

PMID- 30196548
TI  - Plasma Amyloid as Prescreener for the Earliest Alzheimer Pathological Changes.
AB  - OBJECTIVE: We investigated the association of plasma amyloid beta (Abeta)40,
      Abeta42, and total tau (tTau) with the presence of Alzheimer pathological changes
      in cognitively normal individuals with subjective cognitive decline (SCD).
      METHODS: We included 248 subjects with SCD (61 +/- 9 years, 42% female, Mini
      Mental State Examination = 28 +/- 2) from the SCIENCe project and Amsterdam
      Dementia Cohort. Subjects were dichotomized as amyloid abnormal by cerebrospinal
      fluid (CSF) and positron emission tomography (PET). Baseline plasma Abeta40,
      Abeta42, and tTau were measured using Simoa technology. Associations between
      plasma levels and amyloid status were assessed using logistic regression analyses
      and receiver operating characteristic analyses. Association of plasma levels with
      risk of clinical progression to mild cognitive impairment (MCI) or dementia was
      assessed using Cox proportional hazard models. RESULTS: Fifty-seven (23%)
      subjects were CSF-amyloid abnormal. Plasma Abeta42/Abeta40 ratio and plasma
      Abeta42 alone, but not tTau, identified abnormal CSF-amyloid status (plasma
      ratio: area under the curve [AUC] = 77%, 95% confidence interval [CI] = 69-84%;
      plasma Abeta42: AUC = 66%, 95% CI: 58-74%). Combining plasma ratio with age and
      apolipoprotein E resulted in AUC = 83% (95% CI = 77-89%). The Youden cutoff of
      the plasma ratio gave a sensitivity of 76% and specificity of 75%, and applying
      this as a prescreener would reduce the number of lumbar punctures by 51%. Using
      PET as outcome, a comparable reduction in number of PET scans would be achieved
      when applying the plasma ratio as prescreener. In addition, low plasma ratio was
      associated with clinical progression to MCI or dementia (hazard ratio = 2.0, 95%
      CI = 1.4-2.3). INTERPRETATION: Plasma Abeta42/Abeta40 ratio has potential as a
      prescreener to identify Alzheimer pathological changes in cognitively normal
      individuals with SCD. Ann Neurol 2018;84:656-666.

PMID- 30196549
TI  - Erratum.

PMID- 30196550
TI  - Screening of known disease genes in congenital scoliosis.
AB  - BACKGROUND: Congenital scoliosis (CS) is defined as a lateral curvature of the
      spine due to the vertebral malformations and has an incidence of 0.5-1/1,000
      births. We previously examined TBX6 in Japanese CS patients and revealed that
      approximately 10% of CS was caused by TBX6 mutations. However, the genetic cause
      of remaining CS is unknown. METHODS: We recruited 78 CS patients without TBX6
      mutations and major comorbidities, and investigated the genes previously reported
      to be associated with CS and congenital vertebral malformations by whole-exome
      sequencing. RESULTS: We identified the compound heterozygous missense variants in
      LFNG in one patient. No likely disease-causing variants were identified in other
      patients, however. LFNG encodes a GlcNAc-transferase. The LFNG variants showed
      loss of their enzyme function. CONCLUSIONS: A LFNG mutation is reported in a case
      of spondylocostal dysostosis (SCD), a skeletal dysplasia with severe
      malformations of vertebra and rib. The CS patient with LFNG mutations had
      multiple vertebral malformations including hemivertebrae, butterfly vertebrae,
      and block vertebrae, and rib malformations. LFNG mutations may cause a spectrum
      of phenotypes including CS and SCD. The current list of known disease genes could
      explain only a small fraction of genetic cause of CS.

PMID- 30196551
TI  - Analysis of clinical outcomes of upper and lower extremity reconstructions in
      patients with soft-tissue sarcoma.
AB  - BACKGROUND AND OBJECTIVES: Primary amputations have been the standard of
      treatment for extremity soft tissue sarcomas. However, over the last few decades,
      this mode of treatment has been increasingly replaced by limb-sparing
      procedures.1 Our goal is to report the clinical outcomes of upper and lower
      extremity reconstructions in patients with a history of soft-tissue sarcoma.
      METHODS: A retrospective review of 178 patients with a history of soft-tissue
      sarcoma who underwent upper or lower extremity reconstructions was conducted.
      Demographics, tumor characteristics, treatment modalities, type of flap utilized,
      functional outcomes, and postoperative donor-/recipient-site complications
      (DSC/RSC) were analyzed. Variables were compared between free and pedicle flaps
      (FF or PF). RESULTS: PF reconstructions had a higher rate of DSC (P < 0.044),
      whereas FF reconstructions had a higher rate of RSC (P < 0.03). Upper extremity
      reconstruction resulted in a mean QuickDASH score of 5.98 (SD 9.37) with no
      significant difference between PF and FF. Lower extremity reconstruction resulted
      in a mean score of 71.2 (SD 10.7) for PF and 71.3 (SD 5.1) for FF on the Lower
      Extremity Function Scale. CONCLUSION: Limb-preserving reconstruction with PF and
      FF is a reliable and safe option after sarcoma resection. In addition, long-term
      outcomes are promising and reassure the adequate functionality of the limb.

PMID- 30196552
TI  - How do genetically disabled adults view selective reproduction? Impairment,
      identity, and genetic screening.
AB  - BACKGROUND: Genomic medicine is rapidly evolving, particularly in the domain of
      reproduction. Population carrier screening for a range of disorders is becoming
      possible using whole genome/exome sequencing. However, very little is known about
      the views of genetically disabled adults toward selective reproduction. METHODS:
      Forty-three in-depth qualitative interviews were carried out with adults living
      with different types of genetic condition, recruited through support groups and
      clinics. Interviews covered participants' experiences of their condition and
      their views toward genetic intervention in reproduction. Thematic analysis of the
      data using NVivo 11 was undertaken, and participants were assigned categories as
      either supporting, not-supporting, or having ambivalent views toward selective
      reproduction. RESULTS: The majority of participants (65%) expressed either
      disapproval of, or held ambivalent views toward, selective reproduction. Key
      reasons for non-support included regarding genetic impairment as part of personal
      identity and the prioritization of social and environmental barrier removal. Key
      reasons for support of selective reproduction included negative and externalizing
      attitudes toward genetic impairment and a belief in the importance of informed
      reproductive decision-making. CONCLUSION: The degree to which participants
      identified with their impairment, more so than how they valued it, was
      significant in determining attitudes toward selective reproduction. Those who
      supported genetic screening viewed their impairment as separate to themselves,
      while participants who considered their impairment as integral to their identity
      were most likely to report ambivalent or negative attitudes. Policymakers and
      stakeholders considering the role of genetic carrier screening panels might
      usefully engage with adults affected by heritable disease as well as disability
      identity politics when considering the acceptability and social impact of genetic
      screening programs.

PMID- 30196553
TI  - Emergency trans-catheter coronary intervention for left main compression
      secondary to pulmonary hypertension in a 4-year-old child.
AB  - Here, we report on the case of a 4-year-old child with large atrial septal defect
      (ASD) and severe pulmonary hypertension presenting an ischemic cardiomyopathy
      secondary to left main (LM) compression by a dilated pulmonary artery trunk.
      Despite of surgical treatment consisting in ASD closure and coronary artery
      bypass grafting, the patient was not weanable from ECMO. Control coronarography
      showed a near-occlusion of the left mammary bypass. A rescue percutaneous LM
      angioplasty with drug-eluting stent implantation was performed.

PMID- 30196554
TI  - Homeopathic medicinal products for preventing and treating acute respiratory
      tract infections in children.
AB  - BACKGROUND: Acute respiratory tract infections (ARTIs) are common and may lead to
      complications. Most children experience between three and six ARTIs annually.
      Although these infections are self-limiting, symptoms can be distressing. Many
      treatments are used to control symptoms and shorten illness duration. Most have
      minimal benefit and may lead to adverse effects. Oral homeopathic medicinal
      products could play a role in childhood ARTI management if evidence for
      effectiveness is established. OBJECTIVES: To assess the effectiveness and safety
      of oral homeopathic medicinal products compared with placebo or conventional
      therapy to prevent and treat acute respiratory tract infections in children.
      SEARCH METHODS: We searched CENTRAL (2017, Issue 11) including the Cochrane Acute
      Respiratory Infections Specialised Register, MEDLINE (1946 to 27 November 2017),
      Embase (2010 to 27 November 2017), CINAHL (1981 to 27 November 2017), AMED (1985
      to December 2014), CAMbase (searched 29 March 2018), British Homeopathic Library
      (searched 26 June 2013 - no longer operating). We also searched the WHO ICTRP and
      ClinicalTrials.gov trials registers (29 March 2018), checked references, and
      contacted study authors to identify additional studies. SELECTION CRITERIA:
      Double-blind, randomised controlled trials (RCTs) or double-blind cluster-RCTs
      comparing oral homeopathy medicinal products with identical placebo or self
      selected conventional treatments to prevent or treat ARTIs in children aged 0 to
      16 years. DATA COLLECTION AND ANALYSIS: We used standard methodological
      procedures expected by Cochrane. MAIN RESULTS: We included eight RCTs of 1562
      children receiving oral homeopathic medicinal products or a control treatment
      (placebo or conventional treatment) for upper respiratory tract infections
      (URTIs). Four treatment studies examined the effect on URTI recovery, and four
      studies investigated the effect on preventing URTIs after one to three months of
      treatment, followed up for the remainder of the year. Two treatment and two
      prevention studies involved homeopaths individualising treatment. The other
      studies used predetermined, non-individualised treatments. All studies involved
      highly diluted homeopathic medicinal products.We found several limitations to the
      included studies, in particular methodological inconsistencies and high attrition
      rates, failure to conduct intention-to-treat analysis, selective reporting, and
      apparent protocol deviations. We assessed three studies as at high risk of bias
      in at least one domain, and many had additional domains with unclear risk of
      bias. Three studies received funding from homeopathy manufacturers; one support
      from a non-government organisation; two government support; one was cosponsored
      by a university; and one did not report funding support.Methodological
      inconsistencies and significant clinical and statistical heterogeneity precluded
      robust quantitative meta-analysis. Only four outcomes were common to more than
      one study and could be combined for analysis. Odds ratios (OR) were generally
      small with wide confidence intervals (CI), and the contributing studies found
      conflicting effects, so there was little certainty that the efficacy of the
      intervention could be ascertained. All studies assessed as at low risk of bias
      showed no benefit from oral homeopathic medicinal products; trials at uncertain
      and high risk of bias reported beneficial effects.We found low-quality evidence
      that non-individualised homeopathic medicinal products confer little preventive
      effect on ARTIs (OR 1.14, 95% CI 0.83 to 1.57). We found low-quality evidence
      from two individualised prevention studies that homeopathy has little impact on
      the need for antibiotic usage (N = 369) (OR 0.79, 95% CI 0.35 to 1.76). We also
      assessed adverse events, hospitalisation rates and length of stay, days off
      school (or work for parents), and quality of life, but were not able to pool data
      from any of these secondary outcomes.There is insufficient evidence from two
      pooled individualised treatment studies (N = 155) to determine the effect of
      homeopathy on short-term cure (OR 1.31 favouring placebo, 95% CI 0.09 to 19.54;
      very low-quality evidence) and long-term cure rates (OR 0.99, 95% CI 0.10 to
      9.67; very low-quality evidence). Adverse events were reported inconsistently;
      however, serious events were not reported. One study found an increase in the
      occurrence of non-severe adverse events in the treatment group. AUTHORS'
      CONCLUSIONS: Pooling of two prevention and two treatment studies did not show any
      benefit of homeopathic medicinal products compared to placebo on ARTI recurrence
      or cure rates in children. We found no evidence to support the efficacy of
      homeopathic medicinal products for ARTIs in children. Adverse events were poorly
      reported, so conclusions about safety could not be drawn.

PMID- 30196555
TI  - Readmission after lung surgery.

PMID- 30196556
TI  - Testicular tumours discovered during infertility workup are predominantly benign
      and could initially be managed by sparing surgery.
AB  - BACKGROUND AND OBJECTIVES: To evaluate the pathological features and recurrence
      of incidental testis tumours treated by partial orchiectomy in a population of
      infertile men. METHODS: We retrospectively pooled, from four andrology referral
      centres, 32 patients diagnosed with testis mass during regular infertility
      workup. Patients included had an impaired sperm analysis and testis sparing
      surgery was performed to prevent secondary azoospermia or androgen therapy.
      RESULTS: Mean age was 36 (IQR, 32 to 37). The mean largest tumoral diameter was
      8.5 mm (IQR, 5 to 10). A total of 25% (8 of 32) of patients had a malignant
      tumour (seminoma, 7 of 32, 22%; teratoma, 1 of 32, 3%) and 75% (24 of 32) had a
      benign lesion (Leydig cell tumour, 23 of 32, 72%; scar tissue, 1 of 32, 3%).
      Malignant tumours were then managed by total orchiectomy (six of eight) or by
      radiotherapy (two of eight). With a mean follow up of 26 months (IQR, 8 to 32),
      one patient (3%) had an homolateral recurrence, which was a Leydig cell tumour.
      Not a single patient developed metastasis. CONCLUSION: Seventy-five per cent of
      the tumours discovered during infertility management were of a benign pathology.
      A conservative approach could be proposed initially to avoid unnecessary
      orchiectomies. Orchiectomy and radiotherapy could be discussed as salvage
      therapies for malignant lesions.

PMID- 30196557
TI  - EC-IC bypass for cerebral revascularization following skull base tumor resection:
      Current practices and innovations.
AB  - Complex skull base tumors can involve critical vessels of the head and neck. To
      achieve a gross total resection, vessel sacrifice may be necessary. In cases
      where vessel sacrifice will cause symptomatic cerebral ischemia, surgical
      revascularization is required. The purpose of this paper is to review cerebral
      revascularization for skull base tumors, the indications for these procedures,
      outcomes, advances, and future directions.

PMID- 30196558
TI  - Surrogate indicators of quality are associated with survival following surgical
      treatment for hepatocellular carcinoma.
AB  - INTRODUCTION: Quality/core measures have been collected for over 10 years.
      Studies have demonstrated hospital performance is related to postoperative
      outcomes. We hypothesize that hospital quality measures are associated with long
      term survival following surgical resection for hepatocellular carcinoma (HCC).
      METHODS: The National Cancer Data Base was queried for all HCC cases. Individual
      hospitals were deidentified. Quality markers were defined as hospital-specific
      median length of stay (LOS), 30-day mortality rate and readmit rate. A Cox
      regression stratified by stage estimated survival. To minimize confounding, a
      landmark analysis was estimated for patients that survived greater than 30 days.
      RESULTS: A total of 16 202 HCC patients underwent surgical resection and 996
      (6.1%) died within 30 days following surgery. Calculated by unique hospital,
      median 30-day death rate was 4.6% (interquartile range [IQR]: 1.2% to 7.6%).
      Thirty-day readmit rate was 2.6% (IQR: 0% to 5.9%) and median LOS was 8.0 days
      (IQR: 6.5 to 9.2). In the multivariate Cox regression, 30-day death rate (hazard
      ratio [HR], 1.89; 95% confidence interval [CI]: 1.32 to 2.71) and longer LOS (HR,
      1.02; 95% CI: 1.01 to 1.02) were associated with worse survival. Higher 30-day
      readmission rate was associated with improved survival (HR, 0.61; 95% CI, 0.38 to
      0.97). CONCLUSIONS: Hospital-level surrogate markers of surgical quality appear
      to be significantly associated with HCC survival following resection. Patients
      treated in higher 30-day mortality centers, experienced worse outcomes.
      Individual hospitals should critically review disease-specific outcomes following
      resection to identify areas for improvement.

PMID- 30196559
TI  - Contrast volume to estimated glomerular filtration rate ratio for prediction of
      contrast-induced acute kidney injury after cardiac catheterization in adults with
      congenital heart disease.
AB  - BACKGROUND: Adults with congenital heart disease (ACHD) are vulnerable to
      contrast-induced acute kidney injury (CI-AKI) after cardiac catheterization. The
      aim of this study was to identify risk factors for clinically significant CI-AKI
      and evaluate the predictive value of contrast volume to estimated glomerular
      filtration rate ratio (V/eGFR) for the risk of CI-AKI following catheterization
      in the ACHD population. METHODS: ACHD patients who underwent catheterization at
      Boston Children's hospital between 1/2011 and 1/2017 were retrospectively
      analyzed. CI-AKI was defined as an increase in serum creatinine >=0.3 mg/dL
      within 48 hr or >=1.5 times baseline within 7 days of procedure. Controls without
      CI-AKI were matched for calendar year of catheterization with cases using a 3:1
      ratio. RESULTS: Of 453 catheterizations meeting inclusion criteria, 27
      catheterizations (5.9%) were complicated by CI-AKI, with dialysis being used to
      manage renal dysfunction in five of these events. Older age, male gender,
      admission prior to catheterization, and V/eGFR ratio were found to be related to
      risk of CI-AKI. Patients with a V/eGFR >= 2.6 had a significantly higher risk of
      CI-AKI (OR = 6.4; 95% CI = 2.0-20.4; P = 0.002). Survival at 3 years post
      catheterization, was significantly shorter for CI-AKI cases compared to controls
      (49% versus 97%; P < 0.001) even in those with return to baseline renal function
      prior to discharge (60% versus 97%, P < 0.001). CONCLUSION: In ACHD patients
      undergoing cardiac catheterization, a higher V/eGFR ratio is a strong predictor
      of clinically significant CI-AKI. Development of CI-AKI is a poor prognostic
      indicator and is associated with decreased survival in this population.

PMID- 30196561
TI  - Central venous catheter care for children with cancer should focus on early
      infections.

PMID- 30196560
TI  - Valve-in-valve-in-valve: Balloon expandable transcatheter heart valve in failing
      self-expandable transcatheter heart valve in deteriorated surgical bioprosthesis.
AB  - Valve-in-valve (ViV) procedures for failing bioprostheses carry a certain risk
      for device malfunction. We herein report a case of a failing Evolut R in a
      deteriorated Mitroflow, treated with a Sapien 3. An 81 year old female patient
      received surgical aortic valve replacement and was treated by ViV due to
      deterioration. Three years later, echocardiography revealed a pressure gradient
      of peak/mean 105/63 mmHg. Subsequently, a second ViV procedure with initial
      intentional rupture of the bioprosthetic stent was performed. Immediate stent
      recoil of the Evolut R prompted implantation of a Sapien 3. In 30-day follow-up,
      mean pressure gradient of 30 mmHg and nearly complete symptom relief was
      documented. Fracture of a surgical bioprosthetic stent is feasible in a ViV
      configuration. Supra-annular placement of a balloon-expandable THV as ViV-in
      valve is feasible with suboptimal hemodynamic results in this case. Risk of re-do
      surgery should be weighted against anticipated hemodynamic and clinical results.

PMID- 30196562
TI  - Malignant granular cell tumor: Clinical features and long-term survival.
AB  - BACKGROUND: Malignant granular cell tumor GCT (mGCT) has not been well described.
      We sought to investigate associations between tumor characteristics, treatments
      and survival. METHODS: Patients diagnosed with mGCT years 1995-2014 were
      identified using the Surveillance, Epidemiology and End Results database.
      Descriptive statistics regarding tumor and treatment characteristics were
      calculated. Chi-square tests determined associations between tumor location and
      features. Survival analyses included Kaplan-Meier functions and Cox proportional
      hazard ratios (HR). RESULTS: Of 113 patients included, median age was 54 years
      and 77.0% were female. Frequent tumor sites included soft tissues (36.3%),
      ovary/testis (16.8%), and skin (11.5%). Median tumor size was 4.0 cm. Metastases
      to regional lymph nodes (12.5%) and distant sites (11.4%) occurred. Treatments
      included surgery (85.0%), radiotherapy (12.4%) and chemotherapy (8.9%). Overall
      five and 10-year cause-specific survival was 74.3% and 65.2%, respectively.
      Survival was worse for patients with tumors >5 cm compared to those with tumors
      <=5 cm (HR = 34.03; 95% confidence interval [CI]: 2.57-450.17), and patients with
      metastasis (HR = 15.25; 95% CI: 1.19-195.72) compared with those without
      metastasis. Patients who underwent surgery had superior survival than those who
      did not (HR = 0.13; 95% CI: 0.05-0.34). CONCLUSIONS: Particular tumor features
      and treatments are associated with superior survival. This information may be
      used to more accurately estimate prognosis.

PMID- 30196563
TI  - Assessing tools for management of noncolorectal nonneuroendocrine liver
      metastases: External validation of a prognostic model.
AB  - INTRODUCTION: Selection criteria and benefits for resection of noncolorectal,
      nonneuroendocrine liver metastases (NCNNELM) remain debated. A prognostic score
      was developed by the Association Francaise de Chirurgie (AFC) for patient
      selection, but not validated. We performed a geographic external validation of
      this score. METHODS: Patients with resected NCNNELM from six institutions (2000
      2014) were assigned risk groups based on the AFC score. Discrimination was
      evaluated by visually inspecting separation of overall survival (OS) curves among
      risk categories. The slope of the continuous score on OS and hazard ratios for
      risk categories were examined. RESULTS: Of 165 patients, 53 (32.1%) were low
      risk, 85 (51.5%) intermediate-risk, and 27 (16.4%) high-risk. The OS curves did
      not separate among risk groups: 5-year OS were 60.1% (low), 57.1% (intermediate),
      and 55.6% (high). The parameter estimate (0.02) indicated lower discrimination
      than in the AFC cohort. Hazard ratios of 1.05 (0.63 to 1.70) for low vs
      intermediate, 0.87 (0.46 to 1.64) for low vs high, and 0.83 (0.46 to 1.49) for
      intermediate vs. high, demonstrated lack of discrimination in OS among risk
      groups. CONCLUSION: While long-term survival is achievable, discrimination of the
      AFC score is not maintained in a geographic external cohort of resected NCNNELM.
      It is not generalizable to this external population.

PMID- 30196564
TI  - Health policy engagement among graduate nursing students in the United States.
AB  - AIM: The aim was to understand how health policy education is currently being
      delivered in the United States' graduate nursing programs. METHODS: This
      exploratory cross-sectional design used an anonymous online survey to target
      graduate nursing students attending American Association of College of Nursing
      (AACN) member institutions. RESULTS: Over 75% of the sample (n = 140) reported
      taking a dedicated health policy course and 71.5% ( n = 131) of the sample
      responded that a health policy course was required and an equal distribution
      among master's and doctoral students. There was no significant difference between
      type of graduate degree sought and the requirement to take a health policy course
      ( P = 0.37). For students involved in health policy, there was a greater
      proportion of master's students involved at the state level, than doctorate of
      nursing practice (DNP) or PhD students ( P = 0.04). CONCLUSIONS: Health policy
      and advocacy education are important aspects of graduate nursing curriculum and
      have been integrated into curricula. Graduate nursing students at all levels
      reported that health policy AACN Essential competencies are being included in
      their program, either as stand-alone health policy courses or integrated health
      policy learning activities during matriculation.

PMID- 30196565
TI  - Effect of mapping biopsy on surgical management of cholangiocarcinoma.
AB  - BACKGROUND: The effect of endoscopic transpapillary mapping biopsy (MB) on
      decision-making of surgical indications, selecting surgical procedures, or
      operative outcomes remains unclear. METHODS: Two-hundred and thirty-four patients
      with cholangiocarcinoma who were evaluated for surgical resection from 2007 to
      2017 were reviewed. MB was performed in 80 patients who underwent tumor
      resection. We examined how MB affected operative indications or modified surgical
      procedures. Operative curability was compared between patients with and without
      preoperative MB. RESULTS: MB resulted in avoidance of noncurative resections in
      eight patients (14%, 8/57) of abandoned laparotomies. Based on the MB, surgical
      procedures were modified in nine patients (11.3%, 9/80), and this was justified
      by pathological examinations in eight patients (88.9%, 8/9). The MB group had an
      improved negative margin rate (83.8% vs 67.5%, P = 0.017) and a lower incidence
      of carcinoma in situ (8.8% vs 20.0%, P = 0.043) at the first cut than the non-MB
      group. The incidence of bile leakage was significantly lower in the MB group in
      both anastomotic site (5.0% vs 16.3%, P = 0.018) and parenchymal surface (2.5% vs
      10.0%, P = 0.043). CONCLUSION: MB is helpful for selecting optimal surgical
      procedure for cholangiocarcinoma and it contributes for safe surgery by securing
      negative bile duct margin on the first cut.

PMID- 30196566
TI  - Validation and refinement of the catheterization RISk score for pediatrics (CRISP
      score): An analysis from the congenital cardiac interventional study consortium.
AB  - OBJECTIVES: To externally validate the CRISP score, and determine if refinements
      might improve clinical utility. BACKGROUND: The CRISP score estimates risk of
      serious adverse events (SAEs) for pediatric catheterization. METHODS: Pediatric
      (age < 18) procedures reported to the Congenital Cardiovascular Interventional
      Study Consortium registry from 05/08 to 09/17 (n = 29,830, 27 centers) were
      divided into a development dataset of 14,784 earlier procedures, and a validation
      dataset of 15,046 more recent procedures. The development dataset was used to
      refit the original CRISP model, and to develop a revised(r) CRISP score,
      consisting of entirely pre-procedurally collected data. The validation dataset
      was then used to compare model fit and risk prediction between CRISP, rCRISP and
      two existing risk scores using Akaike's (AIC), Schwarz's (BIC) Bayes Information
      Criteria, -log Likelihood (N2LL), area under the receiver operator curve and chi
      square goodness-of-fit statistic (across 5 risk categories). RESULTS: Overall
      4.31% of patients experienced at least one SAE with frequency increasing from
      1.08% in CRISP category 1 to 27.34% in category 5. Both CRISP and rCRISP
      (entirely pre-procedural) predicted risk of SAEs well, with observed to predicted
      ratios ranging from 0.71 to 1.18 across the 5 risk categories. Compared to the
      original CRISP score, rCRISP demonstrated less optimal model fit (higher AIC,
      BIC, and N2LL) but similar risk prediction (C-statistic = 0.71 vs. 0.70; chi
      squared statistic = 6.77 vs. 6.85). CONCLUSION: The CRISP score accurately
      predicts procedural risk. With minor modifications, the revised version (rCRISP)
      performed well with arguably greater clinical utility as an entirely
      preprocedural risk model.

PMID- 30196567
TI  - Radiation therapy damages external anal sphincter and perineal muscle floor.

PMID- 30196568
TI  - Feasibility and clinical outcome of rotational atherectomy in patients presenting
      with an acute coronary syndrome.
AB  - OBJECTIVES: We aimed to investigate the feasibility, safety, and outcome of
      rotational atherectomy (RA) in the setting of acute coronary syndrome (ACS).
      BACKGROUND: Limited data are available on the use of RA in patients presenting
      with ACS. METHODS: This analysis is from an observational registry, which
      enrolled all consecutive patients undergoing RA in a tertiary center. Between
      2002 and 2015, 433 patients with stable coronary artery disease (SCAD) were
      treated with RA. Within the same period, 108 patients with ACS (8 STEMI and 100
      NSTE-ACS) were treated with RA. Procedural success was similar between the ACS
      and the SCAD groups (96.6% vs. 96.4%, P = 0.90), and no significant difference
      was observed in procedural complications (slow-flow: 0.8% vs. 2.8%, P = 0.32;
      coronary dissection: 6.8% vs. 7.2%, P = 1.00; coronary perforation: 0.8% vs.
      1.7%, P = 0.69). In-hospital MACE rates were comparable (3.7% vs. 3.2%, P =
      0.77). The risk of MACE within 24 months was higher in ACS patients (39.9% vs.
      22.4%, log-rank P = 0.002; HR: 1.39; 95% CI: 1.12-1.73; P = 0.003). Multivariable
      Cox regression analysis identified left ventricular ejection fraction (HR 0.97;
      95% CI: 0.85-0.99; P = 0.001), treatment with a BMS (HR 2.22, 95% CI: 1.15-4.25,
      P = 0.02) or early generation drug eluting stent (HR 1.99; 95% CI 1.09-3.64; P =
      0.03), as well as ACS presentation (HR 1.53; 95% CI: 1.02-2.29; P = 0.04) as
      predictors of MACE at two years. CONCLUSIONS: RA is technically feasible and safe
      in high risk patients presenting with ACS. However, successful application of RA
      did not mitigate the higher rate of long term cardiovascular events.

PMID- 30196569
TI  - Shake No Bake: A Homemade Ultrasound Gel Recipe for Low-Resource Settings.
AB  - Commercially produced ultrasound coupling gel is often a scarce resource in rural
      regions of low-income countries that use sonography as their main imaging
      modality and, when available, may be cost prohibitive. Various homemade gels were
      created and tested to assure image quality was not compromised. Glucomannan-based
      gel and guar gum-based gel had superior physical properties in initial testing
      and showed no substantial difference compared with commercially available
      ultrasound gel on subject and phantom imaging and analysis (P > .05 using a 1
      tailed sign test). Neither gel required heating, attracted insects, damaged
      ultrasound transducers, stained samples of clothing, or had harmful effects to
      subjects.

PMID- 30196571
TI  - NARCA: A novel prognostic scoring system using neutrophil-albumin ratio and Ca19
      9 to predict overall survival in palliative pancreatic cancer.
AB  - BACKGROUND AND OBJECTIVES: Several serum based-markers and ratios have been
      investigated for their prognostic value in pancreatic ductal adenocarcinoma
      (PDAC). This cohort study aimed to combine these into a novel prognostic scoring
      system. METHODS: A retrospective cohort study was performed on 145 patients with
      unresectable histologically-confirmed PDAC. Based on the existing literature the
      following markers were investigated: neutrophil-lymphocyte ratio (NLR),
      neutrophil-albumin ratio (NAR), platelet-lymphocyte ratio (PLR), fibrinogen, and
      Ca19-9. These values were dichotomized about their medians for Kaplan-Meier and
      Cox regression analysis. RESULTS: Univariate Cox regression revealed
      statistically significant prognostic value for: NLR, NAR, PLR, fibrinogen, and
      Ca19-9. When combining these using Cox regression analysis adjusting for other
      prognostic indicators, only NAR (hazard ratios [HR] = 3.174, P = 0.022) and Ca19
      9 (HR = 2.697, P = 0.031) were independent predictors of survival. Combining NAR
      and Ca19-9 we split the cohort into three "NARCA" groups: NARCA0 = NAR <= 0.13
      and Ca19-9 <= 770, NARCA1 = either NAR > 0.13 or Ca19-9 >770, NARCA2 = NAR > 0.13
      and Ca19-9 > 770. Median survival was 20.5, 9.7 and 4.1 months in NARCA0, 1, and
      2 respectively ( P < 0.0005, log-rank test). A separate validation cohort
      confirmed the prognostic significance of the score ( P = 0.048). CONCLUSIONS:
      Combining NAR and Ca19-9 into a prognostic score allows stratification of
      unresectable PDAC patients into groups with significantly different overall
      survival.

PMID- 30196572
TI  - MAGnesium-based bioresorbable scaffold and vasomotor function in patients with
      acute ST segment elevation myocardial infarction: The MAGSTEMI trial: Rationale
      and design.
AB  - AIM: Use of a Bioresorbable Scaffolds (BRS) either in clinical practice or in the
      setting of an acute myocardial infarction (MI) is controversial. Despite an
      overall high rate of thrombosis, vascular healing response following BRS
      implantation tend to superiority as compared to metallic drug-eluting stent in ST
      segment elevation myocardial infarction (STEMI) patients. We sought to compare
      the in-stent/scaffold vasomotion between metallic BRS and sirolimus eluting stent
      (SES) at 12-month angiographic follow-up in the setting of patients with STEMI
      treated by primary PCI. STUDY DESIGN: This is an investigator-driven,
      prospective, multicenter, randomized, single blind, two-arm, controlled trial
      (ClinicalTrials.gov number: NCT03234348). This trial will randomize ~148 patients
      1:1 to SES or BRS. Primary end-point is the in-stent/scaffold change in mean
      lumen diameter after nitroglycerin administration at 12-month angiographic follow
      up. Besides, patient-oriented combined endpoint of all-cause death, any MI, and
      any revascularization, together with scaffold/stent thrombosis rate and device
      oriented endpoint of cardiac death, target vessel (TV)-MI and TVR at 1 year will
      be also evaluated. Clinical follow-up will be scheduled yearly up to 5 years.
      CONCLUSION: This trial will shed light on the vascular vasomotion following BRS
      implantation in the complex scenario of STEMI.

PMID- 30196573
TI  - Effect of non-compliant balloon postdilatation on magnesium-based bioresorbable
      vascular scaffolds.
AB  - BACKGROUND: Optimal implantation results of bioresorbable scaffolds (BRS) are
      typically assumed to require postdilatation with non-compliant (NC) balloons to
      achieve full scaffold apposition and minimize event rates. We systematically
      evaluated the mechanical effect of NC balloon postdilatation on magnesium-based
      BRS (Magmaris(r), Biotronik AG, Bulach, Switzerland) in vivo. METHODS: In 35
      patients, 40 Magmaris(r) BRS were implanted to treat 37 de novo coronary artery
      stenoses. A systematic implantation protocol was followed. After appropriately
      sized NC balloon predilatation (1:1:1 vessel:balloon:scaffold ratio), Magmaris(r)
      BRS were implanted with a pressure of 10 atm, followed by NC balloon
      postdilatation at nominal BRS size (standardized at 16 atm). OCT was performed
      before and after postdilatation and OCT images were analyzed at a spacing of 0.2
      mm to measure BRS dimensions and determine apposition as well as to detect strut
      fractures. RESULTS: PCI with Magmaris(r) BRS (mean diameter: 3.21 +/- 0.32 mm;
      mean length: 20 +/- 4 mm) was successful in all cases, in one case a non-flow
      limiting distal edge dissection occurred after implantation and before
      postdilatation. NC balloon postdilatation led to significantly larger mean
      scaffold diameter (3.21 +/- 0.32 mm vs. 2.80 +/- 0.39 mm, P < 0.001), abluminal
      scaffold area (7.92 +/- 1.43 mm2 vs. 6.72 +/- 1.28 mm2 , P < 0.001) and lumen
      area (7.58 +/- 1.1 mm2 vs. 6.83 +/- 1.12 mm2 , P < 0.001). Incomplete scaffold
      apposition area was significantly lower if postdilatation was performed (0.01 +/-
      0.04 mm2 vs. 0.17 +/- 0.11 mm2 , P < 0.001). Strut fractures could neither be
      observed before nor after postdilatation. CONCLUSION: NC balloon postdilatation
      of Magmaris(r) BRS is required to achieve optimal expansion. It significantly
      reduces malapposition and can safely be performed without relevant rates of strut
      fracture.

PMID- 30196574
TI  - Plant-microbe competition: does injection of isotopes of C and N into the
      rhizosphere effectively characterise plant use of soil N?
AB  - Despite considerable attention over the last 25 yr, the importance of early
      protein breakdown products to plant nitrogen (N) nutrition remains uncertain. We
      used rhizosphere injection of 15 N-, 13 C- and 14 C-labelled inorganic N and
      amino acid (l-alanine), with chase periods from 1 min to 24 h, to investigate the
      duration of competition for amino acid between roots (Triticum aestivum) and soil
      microorganisms. We further investigated how microbial modification of l-alanine
      influenced plant carbon (C) and N recovery. From recovery of C isotopes, intact
      alanine uptake was 0.2-1.3% of added. Soil microbes appeared to remove alanine
      from soil solution within 1 min and release enough NH4+ to account for all plant
      15 N recovery (over 24 h) within 5 min. Microbially generated inorganic or keto
      acid C accounted for < 25% of the lowest estimate of intact alanine uptake. Co
      location of C and N labels appears a reasonable measure of intact uptake.
      Potential interference from microbially modified C is probably modest, but may
      increase with chase period. Similarly, competition for l-alanine is complete
      within a few minutes in soil, whereas NO3- added at the same rate is available
      for > 24 h, indicating that long chase periods bias outcomes and fail to
      accurately simulate soil processes.

PMID- 30196575
TI  - Transfemoral aortic valve implantation following lithoplasty of iliac artery in a
      patient with poor vascular access.
AB  - Transfemoral approach is considered the preferred route to perform transcatheter
      aortic valve implantation (TAVI) by most operators due to the low invasiveness
      and good outcome, as compared to non-transfemoral approach. However, transfemoral
      access is not always feasible particularly in patients with small and calcific
      vessels. Recently, catheter-based lithoplasty has emerged as a new technique
      based on the use of circumferential pulse pressure waves to disrupt calcific
      plaques. This technology may help to expand eligibility for transfemoral TAVI to
      patients with calcific ileo-femoral vessels and at high risk for non-transfemoral
      approach. We present the case of an 87-year-old woman with poor vascular access
      who successfully underwent transfemoral TAVI following lithoplasty of iliac
      artery.

PMID- 30196576
TI  - Caffeine content of pre-workout supplements commonly used by Australian
      consumers.
AB  - The stimulant properties of caffeine are often promoted in pre-workout
      supplements (PWS) to assist with training, reduce the perception of fatigue, and
      for some brands, assist body fat loss. While manufacturers of PWS often indicate
      the inclusion of significant amounts of caffeine, no independent verification of
      the caffeine content of these products exists. The aim of this investigation was
      to independently assess the caffeine content of popular PWS in Australia and
      compare these values to nutrition information panel data. Fifteen PWS were tested
      for their caffeine content (both within and between batches of the same product).
      The caffeine content of selected PWS ranged from 91 to 387 mg.serve-1 . Only 6 of
      the 15 PWS nutrition information panels included details on caffeine content. The
      percent of caffeine present ranged from 59% to 176% of packaging claims. All but
      one PWS contained a variation of caffeine within and between batches that was
      considered "practically" significant (ie, >=40 mg.serve-1 variation). Consumers
      are likely to be exposed to large and variable caffeine doses if ingesting PWS.
      Product information panels do little to improve consumer awareness of likely
      caffeine intakes.

PMID- 30196577
TI  - Predicting the Onset of Nonlinear Pharmacokinetics.
AB  - When analyzing the pharmacokinetics (PK) of drugs, one is often faced with
      concentration C vs. time curves, which display a sharp transition at a critical
      concentration Ccrit . For C > Ccrit , the curve displays linear clearance and for
      C < Ccrit clearance increases in a nonlinear manner as C decreases. Often, it is
      important to choose a high enough dose such that PK remains linear in order to
      help ensure that continuous target engagement is achieved throughout the duration
      of therapy. In this article, we derive a simple expression for Ccrit for models
      involving linear and nonlinear (saturable) clearance, such as Michaelis-Menten
      and target-mediated drug disposition (TMDD) models. Study Highlights.

PMID- 30196578
TI  - Radioprotective strategies for interventional echocardiographers during
      structural heart interventions.
AB  - OBJECTIVE: We investigated radioprotective strategies for the interventional
      echocardiographer (IE) during structural heart interventions in comparison with
      the interventional cardiologist (IC). BACKGROUND: Structural heart interventions
      are expanding in complexity with increased reliance on IE. Recent reports have
      demonstrated concerning exposure and higher radiation to the IE. METHODS: We
      monitored 32 structural interventions - 19 transcatheter aortic valve
      replacements (TAVR), 6 transcatheter mitral valve repairs, 5 paravalvular leak
      closures, and 2 atrial septal defect closures. Seventeen utilized transesophageal
      echocardiography (TEE) while 15 used transthoracic echocardiography (TTE).
      Members of the IC and IE teams wore multiple dosimeters on different sites of the
      body to measure radiation dose to the total body, lens of the eye, and hand.
      During each case, IE utilized dedicated radiation shielding. RESULTS: Mean doses
      were higher for the primary IC than the primary IE: IC#1-99, 222, 378; IE#1-48,
      52, 416 (body, lens, and hand doses in MUSv). IE radioprotective strategies were
      able to reduce body and lens doses compared to IC during both TTE and TEE-guided
      procedures. Hand equivalent dose remained higher for the IE driven by exposure
      during TEE-guided procedures (IC#1 294 vs. IE#1 676 MUSv). In a subgroup using
      radioprotective drapes during TTE-guided TAVR, IC dose was reduced without effect
      on the IE. CONCLUSIONS: Radiation exposure during structural heart interventions
      is concerning. With dedicated shielding, IE received lower doses to the body and
      lens than IC. Further optimization of structural suite design and shielding is
      needed.

PMID- 30196579
TI  - The effect of preoperative treatments on lymph node counts after total
      gastrectomy in esophagogastric adenocarcinoma.
AB  - OBJECTIVES: This study aims to explore the effects of preoperative treatments on
      lymph nodes (LNs) counts after total gastrectomy with D2 lymphadenectomy in
      esophagogastric adenocarcinoma. METHODS: A retrospective analysis was performed
      for 446 patients with locally advanced esophagogastric adenocarcinoma. The
      patients were divided into three groups: surgery first (SF), preoperative
      chemotherapy (PCT), and preoperative chemoradiotherapy (PCRT). Clinical
      pathological data were analyzed. RESULTS: The case number in SF, PCT, and PCRT
      groups was 281, 109, and 56, respectively, and the median total LNs count was
      32.0 (10.0-102.0), 31.0 (12.0-62.0), and 25.5 (10.0-50.0), respectively, (P <
      0.001). Univariate and multivariate analyses demonstrated the total LNs count was
      lower in PCRT than SF/PCT (P < 0.001), and had no correlation with tumor
      regression grades (TRGs). Subgroup comparison showed radiation target LNs count
      was lower in PCRT than SF/PCT (P < 0.001), and peritarget LNs count was lower in
      PCRT than SF (P = 0.002). CONCLUSION: For esophagogastric adenocarcinoma, PCRT
      reduced total LNs count after total gastrectomy with D2 lymphadenectomy, whereas
      PCT did not. In the PCRT group, LNs count was lower in both radiation target and
      peritarget areas than in the SF group but only in radiation target area than in
      the PCT group. The correlation between TRGs and total LNs count remained unclear.

PMID- 30196580
TI  - A comprehensive educational approach to improving NCLEX-RN pass rates.
AB  - BACKGROUND: Nurse educators strive to find the best educational methods to
      prepare students in their attempt to pass the National Council Licensure
      Examination for Registered Nurses (NCLEX-RN). The purpose of this study is to
      describe the implementation of an online coaching program with Appreciative
      Advising and Emotional Intelligence education as combined educational strategies
      to improve student learning outcomes. METHODS: The study was conducted at a
      university in the Midwestern United States. The sample consisted of students in
      four graduating classes (2013, n = 15; 2014, n = 19; 2015, n = 18; and 2016, n =
      17), who had followed supplemented program preparation in a prelicensure program.
      Electronic surveys were disseminated to determine satisfaction with student
      program supports through analysis of the mean overall average scoring of seven
      point Likert scale rates. NCLEX-RN actual pass rates were reviewed to examine the
      quality of online coaching toward student preparation via a t test to compare the
      mean NCLEX-RN pass rates before and after implementation. RESULTS: The students
      reported satisfaction with the additions of Appreciative Advising and Emotional
      Intelligence. NCLEX-RN pass rates showed significant improvements with the
      combined program support additions. CONCLUSION: The findings suggest that nursing
      schools that include student program support with an online coaching program can
      result in positive trends related to NCLEX-RN pass rates.

PMID- 30196581
TI  - One-stop shop: Simultaneous direct mitral annuloplasty and percutaneous mitral
      edge-to-edge repair in a patient with severe mitral regurgitation.
AB  - Percutaneous edge-to-edge repair of severe mitral regurgitation has been
      established as an alternative treatment option for patients at high risk for
      cardiac surgery. More recently, the introduction of the Cardioband system enabled
      percutaneous direct annuloplasty. Here, we present a case of simultaneous
      percutaneous direct annuloplasty with edge-to-edge repair. Moreover, annuloplasty
      did facilitate clip implantation bei approximating the anterior and posterior
      mitral leaflet. In conclusion, the combination of direct annuloplasty with edge
      to-edge repair is feasible in a single procedure.

PMID- 30196582
TI  - [The Effect of Ambient Temperature on Human Head's Surface Skin Temperature].
AB  - It is important to understand heat loss from human head because human head
      produces much heat for its high metabolism, it also functions as a heat radiator
      to keep body heat balance. Heat loss from human head is closely related to its
      skin temperature. Therefore, skin surface temperature of human head changes with
      ambient temperature is studied. In this research, several positions were sampled
      and the advanced infrared detectors (the infrared thermal imager and the infrared
      thermometer) were used as tools for measurement. For the sake of comparison, the
      young volunteers were grouped into the boys team and the girls team. Results
      showed that, firstly, between the groups, there was only a little difference in
      that girls' head temperature was a little higher; secondly, head temperature of
      either girls or boys rises with air temperature till about 30 C; and thirdly,
      exercise has only a little effect on the head temperature variation. This
      research is practical for further investigation on head heat flow and referential
      for health diagnosing by comparing the data recorded in this experiment.

PMID- 30196583
TI  - [Research on Visual Perception-Referenced Compression Method for Multi-Spectral
      Data with High-Fidelity].
AB  - Aim In order to maintain the chromaticity precision in the process of linear
      compression of the multispectral data, a visual perception-referenced compression
      method (VPCM) based on the chroma gradient (refer to the partial derivative of
      chroma to wavelength) is proposed. Method The method firstly successfully
      developed the transfer functions which could synchronously fusion the spectral
      features and chromaticity characteristics of human visuals based on the nonlinear
      analytic feature of human visual system. For further improvement the transfer
      function, a modified optimizing function was developed to help find out the
      optimal transfer direction for different sample sets. If the transfer function
      was finally settled, it will be applied to transforming the spectral data of the
      sample set (Gamma(S)=C). Then the transformed spectral data of the sample set
      will be compressed with high chromatic accuracy by the principle components
      analysis method. After that, the compressed data will be reconstructed through
      inverse transformation (Gamma(-1)(C)=), while the reconstructed spectral data
      will be using to evaluate the effective of the proposed VPCM method. Result Four
      groups typical and representative sample sets were chosen to test the effective
      of the proposed method. The CIELab color difference in the D50/2 degrees 
      calculates condition and a proposed mean metamerism index (MMI) calculated with
      75 groups typical light sources (including tungsten, fluorescent and LED lamp)
      was adopted as evaluating metrics. Eventually, the comparative experiment
      involving several existing methods Lab-PQR and 2-XYZ indicates that the proposed
      VPCM hold the best chromatic accuracy both for metric MMI and the average color
      difference DeltaE(ab) when compared with Lab-PQR and 2-XYZ, and the spectral
      accuracy was calculated between Lab-PQR and 2-XYZ with Lab-PQR maintained the
      highest spectral accuracy. Conclusion The proposed VPCM can preserve high
      compression chromatic precision at the price of small loss of spectral precision
      and possess good colorimetric stability under variable reference conditions. It
      is very applicable for some application fields which require compressing of the
      multi-spectral data with high chromatic accuracy.

PMID- 30196584
TI  - [Study on the Distinguishment of Camouflage Paints Based on Depolarization
      Characteristics].
AB  - As an important part in the modern warfare, camouflage technology plays a
      critical role in the battlefield, and the results of detection of camouflage
      target directly affect the results of war. However, there is little paper to
      detect camouflage paint by depolarization characteristics, so it is of great
      significance to use the depolarization technology to study the distinguishment of
      camouflage paints. To address this issue, we studied the mechanism of the
      scattering of electromagnetic wave, and analysed the relationship between the
      characteristics of depolarization and mechanism of scattering. Jones Matrix and
      Mueller Matrix were used to set up the physical model, and the Mueller-Jones
      Matrix was decomposed with the characteristics of polarization, then the
      depolarization coefficients(omegad) of the surfaces of the samples was acquired.
      In this experiment, we measured soil and three kinds of camouflage yellow paints
      in seven different incident angles to analyze the characteristics of depolazation
      of the soil and three kinds of camouflage yellow paints' surfaces. Finally, we
      applied the theory of Fresnel formulas to verify the theoretical model. The
      results showed that: the depolarization coefficients of the samples' surfaces
      were related to the scattering, and with the increase of the incident angles, the
      depolarization coefficients were decline. But in the whole measurement process,
      the depolarization coefficients of the soil were far above the camouflage
      paints'. Research indicated that: this article was the first paper which used the
      depolarization coefficients as an important parameter to identify the camouflage
      targets, and could identify the camouflage yellow paints in the soil-background
      accurately and effectively. The processes of the experiments were simpler, and
      the time was shorter. In modern battlefield, it could identify the camouflage
      targets quickly and easily, and furnish the precious time for the victory of the
      war. Therefore, the depolarization technology had a great application value, and
      the paper had very important significance on the development of camouflage
      recognition technology.

PMID- 30196585
TI  - [Modeling and Predicting of MODIS Leaf Area Index Time Series Based on a Hybrid
      SARIMA and BP Neural Network Method].
AB  - The modeling and predicting of vegetation Leaf area index (LAI) is an important
      component of land surface model and assimilation of remote sensing data. The
      MODIS LAI product (i.e. MOD15A2) is one of the most widely used LAI data sources.
      However, the time series of MODIS LAI contains some data of low quality. For
      example, because of the influence of the cloud, aerosol, etc., the MODIS LAI
      presents the characteristics of the discontinuous in time and space. In fact, the
      time series of MODIS LAI include both linear and nonlinear components, which
      cannot be accurately modeled and predicted by either linear method or nonlinear
      method alone. In this paper, the original LAI time series data were first
      smoothed with Savitzky-Golay (SG) filtration and linear interpolation; SARIMA, BP
      neural network and a hybrid method of SARIMA-BP neural network were then used for
      modeling and predicting MODIS LAI time series. The SARIMA-BP neural network
      combined both SARIMA and BP neural network, which could model the linear and the
      nonlinear component of MODIS LAI time series respectively. That is, the final
      result of SARIMA-BP neural network was the sum of results of the two methods.
      Experiments showed that the time series of MODIS LAI that were smoothed with the
      SG filtration and linear interpolation were more smooth than original time
      series, with a determination coefficient up to 0.981, closer to 1 than that of
      SARIMA (0.941) and BP neural network (0.884); the correlation coefficient between
      SARIMA-BP neural network and the observation is 0.991, higher than that of
      between SARIMA (0.971) or BP neural network (0.942) SARIMA and the observation.
      Thus, it can be concluded that, the proposed SARIMA-BP neural network method can
      better adapt to the LAI time series, and it outperforms the SARIMA and BP neural
      network methods.

PMID- 30196586
TI  - [Sensitive Bands Extraction and Prediction Model of Tomato Chlorophyll in Glass
      Greenhouse].
AB  - In order to predict the content of chlorophyll in tomato rapidly and accurately,
      this study, with spectrum technology, focused on the extraction of sensitive
      spectral bands of tomato chlorophyll in glass greenhouse environment and created
      an effective estimation model. During the period of cultivating tomatoes, leaf
      spectra were measured with an ASD FieldSpec HH spectrophotometer and chlorophyll
      content was measured with Type 752 UV-Vis spectrophotometer. Based on the
      original spectra, absorbance spectra, first derivative spectra and continuum
      removal spectra, spectral data was preprocessed, in which the effectiveness of
      spectral features of chlorophyll content of tomato was highlighted and spectral
      response characteristics of the absorbance spectra in the visible part was
      enhanced. It was shown that both the continuum removal spectra and the first
      derivative spectra have strong blue and red absorption valley and green
      reflection peak. In this paper, the original spectrum, absorbance spectrum, first
      derivative spectrum and continuum removal spectrum were analyzed and compared,
      and then optimal spectral feature parameters were extracted with methods of Inter
      Correlation analysis and multivariate collinearity diagnosis. Sensitive bands
      from original spectrum are 639, 672, 696, 750 and 768 nm. Sensitive bands from
      absorbance spectrum are 638, 663, 750 and 763 nm. Sensitive bands from first
      derivative spectrum are 516, 559 and 778 nm. Sensitive bands from continuum
      removal spectrum are 436, 564, 591, 612, 635, 683 and 760 nm. The stepwise
      multiple regressions were used to develop the prediction models of the
      chlorophyll content of tomato leaf. The result showed that the prediction model,
      which used the values from continuum removal spectrum at 436, 564, 591, 612, 635,
      683, 760 nm as input variables, had the best predictive ability. The calibration
      R-Square was 0.88 and the validation R-Square was 0.82.

PMID- 30196587
TI  - [Identification of Fertilized Chicken Eggs Based on Visible/Near-Infrared
      Spectrum During Early Stage of Incubation].
AB  - In the process of chicken egg hatching, some eggs can not be hatched successfully
      due to the absence of fertilization. These eggs not only cause a lot of waste,
      but also infect other normal eggs with bacteria. In the study, the fertilized
      eggs and clear eggs is identified by using the visible/near-infrared spectrum. It
      is of great necessity to get the best time of identifying the clear eggs in the
      early of hatching, so the variation of eggs' quality in the condition of hatching
      over time is studied. The results show that eggs are fresh after 24 hours'
      hatching and eggs can not be eaten after 72 hours' hatching while the best time
      of identification is within 36 hours. Static acquisition system is developed
      based on visible/near-infrared transmission spectrum for acquiring spectrum.
      Comparing the effect of the model of the different samples of same breed and
      samples of different breed, the different part of spectrum among fertilized eggs
      and clear eggs is deleted which caused by the color of eggshell and yolk, the
      effective spectral band are 355~590 and 670~1 025 nm. Adopting the pretreatment
      of PCA and comparing the accuracy of the various mathematical models with
      different time and the number of principal components decide the best number of
      principal components. Considering the production efficiency and comparing the
      different pretreatment methods of spectrum, for examples, SNV, MSC, Derivative
      correction and PCA, and various mathematical models are combined to establish the
      most efficient discriminant model. The result shows that the most efficient
      discriminant model is established with Fisher and based on the pretreatment of
      PCA after 24 hours' hatching. And the precision rate is 87.18%. The study
      provides a new way for nondestructive and online identification of the fertilized
      eggs and clear eggs.

PMID- 30196588
TI  - [New Algorithms to Separate the Contribution of Petroleum Substances and
      Suspended Particulate Matter on the Scattering Coefficient Spectrum from Mixed
      Water].
AB  - In the water with petroleum pollution, the petroleum will be adsorbed on the
      surface of suspended particulate matter and form a double-layer structure, which
      impacts on the spectrum characteristics to the scattering coefficient. It is a
      key to improve the accuracy of the scattering theory model that the contribution
      of petroleum substances and suspended particulate matter on the scattering
      spectrum coefficient is be separated. A backward scattering coefficient spectrum
      measurement system was being built from linkage observation of three kinds of
      instruments, including DAWN HELEOS II18 angle scattering measuring instrument
      (Wyatt company, American), LISST-100-xB size instrument(SEQUOIA SCIENTIFIC, INC,
      American), HydroScat-6 Sprctral Backscattering Sensor (HS6) ( Hobilabs company,
      American). Many parameters were measured such as voltage value of the scattering
      intensity, the particle size distribution, particle concentration and backward
      scattering coefficient in different water samples. Using the Mie scattering
      theory, a new algorithm to separate the scattering coefficient spectrum and new
      way of thinking to calculate volume scattering function beta(lambda, theta) of
      the unknown refractive index material were proposed. The matching experiments
      were done by selecting quartz sand as particles whose refractive index (m) is
      known and petroleum sewage collected from different oilfield area. On the basis
      of matching experiments different water samples with different properties were
      obtained and related data were determinated. Firstly, according to Mie scattering
      theory the water volume scattering function beta(lambda, theta) for each sample
      is calculated. Secondly, the equation was set up which can convert the scattering
      intensity corresponding to the voltage value V(theta) measured by DAWN HELEOS II
      18 Angle laser scattering instrument into volume scattering function beta(lambda,
      theta). Thirdly, according to the method of optimum the equivalent refractive
      index (mos) of the oil sands mixed and the refractive index (mo) of petroleum
      sewage were estimated; Finally, using beta(lambda, theta) and estimation of mos
      values and mo values to calculate the backscatter coefficient bb(lambda) of all
      kinds samples, and new algorithms were set up which seperated quartz sand bb,
      s(lambda) and petroleum sewage bb, o(lambda) from mixed water with petroleum and
      sands respectively. The establishment of these separation algorithms improves the
      accuracy of the scattering theory model of the water petroleum pollution, on the
      other hand expands the Mie scattering theory in the application of ocean color
      remote sensing.

PMID- 30196589
TI  - [Degradation Characteristics of Spectral Analysis of Straw Nursery Containers in
      Situ Soil Culture].
AB  - This paper aimed to reveal the degradation behavior of a new type of
      biodegradable containers. The biodegradable containers, which was made of
      modified soybean adhesive and straw, was processed in situ biodegradation under
      natural condition. The physicochemical property and microstructure of straw
      nursery containers treated and untreated were characterized with Cellulose
      Tester, Fourier Transform Infrared Spectroscopy (FTIR), Scanning Electron
      Microscope - Energy Dispersive X-ray Spectroscopy (SEM-EDS), and Thermo
      gravimetry Analysis (TGA), respectively. The results indicated that the content
      of cellulose, hemicellulose and lignin of treated specimen decreased to 21.43%,
      21.41% and 9.54% from 29.03%, 30.44% and 12.52%, respectively, comparing with
      those of untreated straw nursery container. FTIR analysis revealed that the ester
      and fat bond have been ruptured, and the aromatic characteristic peak became
      weakened. SEM-EDS spectrum showed the microfibril chain in the container has been
      fragmentation, and the soybean adhesive was also degradation. The surface of
      container appeared oxidization degradation. TGA analysis showed that a large
      number of small molecules have been produced in the process of degradation and
      the thermo-stability of treated samples improved.

PMID- 30196590
TI  - Emodin Successfully Inhibited Invasion of Brucella abortus Via Modulting
      Adherence, Microtubule Dynamics and ERK Signaling Pathway in RAW 264.7 Cells.
AB  - The aim of this work is to investigate the protective efficacy of emodin, an
      active, naturally-occurring anthraquinone derivative of several traditional
      Chinese herbs, against Brucella abortus infection in macrophages. Brucella were
      incubated with different concentrations of emodin and showed that bacterial
      survival rates were markedly reduced in a dose-dependent manner at increasing
      incubation time points. Through bacterial infection assay, the highest non
      cytotoxic concentration of emodin demonstrated attenuated invasion of Brucella
      into macrophages, however it did not inhibit the growth of these pathogens within
      the host cells. On the other hand, emodin effectively decreased the number of
      bacteria that adhered to host cells, which indicated its potential as an anti
      adhesin agent. Furthermore, using immunoblotting and FACS assay for detecting
      MAPK signaling proteins and F-actin polymerization, respectively, the results
      showed that the emodin-incubated cells displayed modest reduction in the
      phosphorylation levels of ERK1/2 and inhibition of F-actin polymerization as
      compared to control cells. These findings indicate the potential use of emodin as
      a naturally-occurring alternative method for the prevention of animal brucellosis
      although this requires confirmation of safe clinical doses.

PMID- 30196591
TI  - Inhibitory Effect of Standardized Curcuma xanthorrhiza Supercritical Extract on
      LPS-Induced Periodontitis in Rats.
AB  - Periodontitis, which is a severe inflammatory disease caused by endotoxins
      secreted from oral pathogens, destructs gingival tissue and alveolar bone.
      Curcuma xanthorrhiza, commonly called Java turmeric, has been shown to possess
      anti-bacterial and anti-inflammatory activities. The present study evaluated the
      inhibitory effect of C. xanthorrhiza supercritical extract (CXS) standardized
      with xanthorrhizol on lipopolysaccharide (LPS)-induced periodontitis in an animal
      model. LPS was topically injected into the periodontium of Sprague-Dawley rats to
      induce periodontitis and CXS (30 and 100 mg.kg-1.day-1) was orally administered
      after day 12. Histologically, CXS inhibited the collapse of gingival tissue by
      preventing cell infiltration. CXS significantly downregulated the expression of
      matrix metalloproteases (MMPs) and inflammation-related biomarkers, such as
      nuclear factor-kappa B (NF-kappaB) and interleukin-1 beta (IL-1beta) in gingival
      tissue. CXS also improved bone remodeling by downregulating osteoclastic
      transcription factors, such as nuclear factor of activated T-cells c1 (NFATc1),
      tartrate-resistant acid phosphatase (TRAP), and cathepsin K. In addition, CXS
      upregulated osteoblast differentiation-related markers, alkaline phosphate (ALP)
      and collagen type I alpha (COLA1). Thus, CXS can ameliorate periodontitis by
      inhibiting inflammation and improving bone remodeling.

PMID- 30196592
TI  - Transcriptional Response and Enhanced Intestinal Adhesion Ability of
      Lactobacillus rhamnosus GG after Acid Stress.
AB  - Lactobacillus rhamnosus GG (LGG) is a probiotic commonly used in fermented dairy
      products. In this study, RNA-sequencing was performed to unravel the effects of
      acid stress on LGG. The transcriptomic data revealed that the exposure of LGG to
      acid at pH 4.5 (resembling the final pH of fermented dairy products) for 1 h or
      24 h provoked a stringent-type transcriptomic response wherein stress response-
      and glycolysis-related genes were upregulated, whereas genes involved in
      gluconeogenesis, amino acid metabolism, and nucleotide metabolism were
      suppressed. Notably, the pilus-specific adhesion genes, spaC, and spaF were
      significantly upregulated upon exposure to acid-stress. The transcriptomic
      results were further confirmed via quantitative polymerase chain reaction
      analysis. Moreover, acid-stressed LGG demonstrated an enhanced mucin-binding
      ability in vitro, with 1 log more LGG cells (p < 0.05) bound to a mucin layer in
      a 96-well culture plate as compared to the control. The enhanced intestinal
      binding ability of acid-stressed LGG was confirmed in an animal study, wherein
      significantly more viable LGG cells (>= 2 log CFU/g) were observed in the ileum,
      caecum, and colon of acid-stressed LGG-treated mice as compared with a non-acid
      stressed LGG-treated control group. To our knowledge, this is the first report
      showing that acid stress enhanced the intestine-binding ability of LGG through
      the induction of pili-related genes.

PMID- 30196593
TI  - Fusarium mangiferae as New Cell Factories for Producing Silver Nanoparticles.
AB  - Finding a safe and broad-spectrum medication is a goal of scientists,
      pharmacists, and physicians, but developing and fabricating the right medicine
      can be challenging. The current study describes the formation of silver
      nanoparticles (AgNPs) by Fusarium mangiferae. It involves the antibiofilm
      activity of the nanoparticles against Staphylococcus aureus. It also involves
      cytotoxic effect against mammalian cell lines. Well-dispersed nanoparticles are
      formed by F. mangiferae. The sizes of the nanoparticles were found to range from
      25 to 52 nm, and UV-Vis scan showed absorption around 416-420 nm. SEM, TEM, and
      AFM results displayed spherical and oval shapes. Furthermore, the FTIR histogram
      detected amide I and amide II compounds responsible for the stability of AgNPs in
      an aqueous solution. AgNPs were observed to decrease the formation of biofilm at
      75% (v/v). DNA reducing, smearing, and perhaps fragmentation were noticed after
      treating the bacterial cells with 50% (v/v). Additionally, cell lysis was
      detected releasing proteins in the supernatant. It was also observed that the
      AgNPs have the ability to cause 59% cervical cancer cell line (HeLa) deaths at
      25% (v/v), however, they showed about 31% toxicity against rat embryo fibroblast
      transformed cell lines (REF). The results of this study prove the efficiency of
      AgNPs as an antibiofilm against S. aureus, suggesting that AgNPs could be an
      alternative to antibiotics. It must also be emphasized that AgNPs displayed
      cytotoxic behavior against mammalian cell lines. Further studies are needed for
      assessing risk in relation to the possible benefit of prescribing AgNPs.

PMID- 30196594
TI  - Proteolytic System of Streptococcus thermophilus.
AB  - The growth of lactic acid bacteria (LAB) generates a high number of metabolites
      related to aromas and flavors in fermented dairy foods. These microbial proteases
      are involved in protein hydrolysis that produces necessary peptides for their
      growth and releases different molecules of interest, like bioactive peptides,
      during their activity. Each genus in particular has its own proteolytic system to
      hydrolyze the necessary proteins to meet its requirements. This review aims to
      highlight the differences between the proteolytic systems of Streptococcus
      thermophilus and other lactic acid bacteria (Lactococcus and Lactobacillus) since
      they are microorganisms that are frequently used in combination with other LAB in
      the elaboration of fermented dairy products. Based on genetic studies and in
      vitro and in vivo tests, the proteolytic system of Streptococcus thermophilus has
      been divided into three parts: 1) a serine proteinase linked to the cellular wall
      that is activated in the absence of glutamine and methionine; 2) the transport of
      peptides and oligopeptides, which are integrated in both the Dpp system and the
      Ami system, respectively; according to this, it is worth mentioning that the Ami
      system is able to transport peptides with up to 23 amino acids while the Opp
      system of Lactococcus or Lactobacillus transports chains with less than 13 amino
      acids; and finally, 3) peptide hydrolysis by intracellular peptidases, including
      a group of three exclusive of S. thermophilus capable of releasing either
      aromatic amino acids or peptides with aromatic amino acids.

PMID- 30196595
TI  - High-Level Production of High-Purity Human and Murine Recombinant Prion Proteins
      Functionally Compatible to In Vitro Seeding Assay.
AB  - Recombinant (rec) prion protein (PrP) is an extremely useful resource for
      studying protein misfolding and subsequent protein aggregation events. Here, we
      report mass production of high-purity rec-polypeptide encoding the C-terminal
      globular domain of PrP; (90-230) for human and (89-231) for murine PrP. These
      proteins were expressed as His-tagged fusion proteins in E. coli cultured by a
      high cell-density aerobic fermentation method. RecPrPs recovered from inclusion
      bodies were slowly refolded under reducing conditions. Purification was performed
      by a sequence of metal-affinity, cation-exchange, and reverse-phase
      chromatography. The current procedure yielded several dozens of milligrams of
      recPrP per liter with >95% purity. The purified recPrPs predominantly adopted an
      alpha-helix-rich conformation and were functionally sufficient as substrates to
      measure the seeding activity of human and animal prions. Establishment of a
      procedure for high-level production of high-purity recPrP supports the
      advancement of in vitro investigations of PrP including diagnosis for prion
      diseases.

PMID- 30196596
TI  - Complete genome of Bacillussubtilis subsp. subtilis KCTC 3135T and variation in
      cell wall genes of B. subtilis strains.
AB  - The type strain Bacillus subtilis subsp.subtilis KCTC 3135T was deeply sequenced
      and annotated, replacing a previous draft genome in this study. The tar and tag
      genes were involved in synthesizing wall teichoic acids (WTAs), and these genes
      and their products were previously regarded as the distinguishing difference
      between B. s. subtilis and B. s. spizizenii. However, a comparative genomic
      analysis of B. subtilis spp. revealed that both B. s. subtilis and B. s.
      spizizenii had various types of cell walls. These tar and tag operons were
      mutually exclusive and the tar genes from B. s. spizizenii were very similar to
      the genes from non-Bacillus bacteria, unlike the tag genes from B. s. subtilis.
      The results and previous studies suggests that the tar genes and the tag genes
      are not inherited after subspecies speciation. The phylogenetic tree based on
      whole genome sequences showed that each subspecies clearly formed a monophyletic
      group, while the tree based on tar genes showed that monophyletic groups were
      formed according to the cell wall type rather than the subspecies. These findings
      indicate that the tar genes and the presence of ribitol as a cell-wall
      constituent were not the distinguishing difference between the subspecies of B.
      subtilis and that the description of subspecies B. s. spizizenii should be
      updated.

PMID- 30196597
TI  - [Immune imbalance: one of the essential issue in sepsis].

PMID- 30196598
TI  - [Timing of antibiotic therapy in patients with sepsis].

PMID- 30196599
TI  - [Sepsis: how to evaluate tissue hypoperfusion in clinical practice].

PMID- 30196600
TI  - [Sepsis: how to assess the clinical value of biomarkers].

PMID- 30196601
TI  - [Consideration and evaluation of sepsis associated coagulopathy].

PMID- 30196602
TI  - [A clinical study of diaphragmatic dysfunction in subjects with mechanical
      ventilation in sepsis].
AB  - Objective: To investigate the prevalence of diaphragmatic dysfunction in
      mechanical ventilated subjects with sepsis and the relationship between
      diaphragmatic dysfunction and clinical outcomes. Methods: Newly intubated
      patients with sepsis diagnosed according to "Sepsis-3" were enrolled from January
      2017 to October 2017 in Intensive Care Unit (ICU) of Sir Run Run Shaw Hospital.
      Diaphragm thickness was recorded ultrasonographically at end-inspiration and end
      expiration when the patients' spontaneous breathing recovered. The diaphragmatic
      thickening fraction (DTF) was calculated as the percentage from the following
      formula: (Thickness at end-inspiration-Thickness at end-expiration) / Thickness
      at end-expiration. The subjects were stratified into a diaphragmatic dysfunction
      group and a non-diaphragmatic dysfunction group based on whether DTF was < 20%.
      Results: Fifty-three subjects were included, and the prevalence of diaphragmatic
      dysfunction was 41.5%(22/53). The diaphragm thickness at end-expiration of the 2
      groups were similar(t=1.328, P>0.05). A significant difference of diaphragm
      thickness at end-inpiration was observed between the 2 groups[(2.2+/-0.4)mm vs.
      (2.8+/-0.8)mm, t=3.677, P<0.05]. Ventilation time after inclusion [(10+/-8)d vs.
      (6+/-5)d, t=2.340, P<0.05], mechanical ventilation durations [(15+/-8)d vs. (11+/
      6)d, t=2.201, P<0.05] and ICU length of stay [(18+/-8)d vs. (14+/-7)d, t=2.039,
      P<0.05]were all significantly longer in the diaphragmatic dysfunction group than
      in the non-diaphragmatic dysfunction group. There was no significant difference
      in the mortality between these 2 groups(chi(2)=0.366, P>0.05). Conclusions:
      Diaphragmatic dysfunction was common in patients with sepsis treated by
      mechanical ventilation and was the consequence of contractile force damages.
      Subjects with such diaphragmatic dysfunction showed longer mechanical ventilation
      durations and ICU stays.

PMID- 30196603
TI  - [Clinical value of Oxford acute severity of illness score in identifying quick
      sequential organ failure assessment-negative patients with sepsis].
AB  - Objective: The quick sequential organ failure assessment (qSOFA) score has been
      proposed as part of diagnostic criteria for sepsis, but there might be an
      underestimation of the incidence of qSOFA-negative sepsis according to a few
      recent studies. The purpose of this study was to evaluate the value of Oxford
      acute severity of illness score (OASIS) in identifying qSOFA-negative (qSOFA<2)
      patients with sepsis. Methods: Sepsis patients with negative qSOFA scores were
      selected from the Medical Information Mart for Intensive Care III(MIMIC-III), a
      database comprising de-identified health-related data from patients staying in
      the critical care units of Beth Israel Deaconess Medical Center between 2001 and
      2012. Non-infectious patients with both qSOFA and SOFA scores less than 2 were
      enrolled as controls. Propensity score matching (PSM) analysis was used to reduce
      the effects of selection bias. Receiver operating characteristic (ROC) curve
      analysis was performed to assess the value of OASIS in discriminating qSOFA
      negative patients with sepsis and to determine its optimal cut-off. Associations
      of OASIS with 28-day mortality after intensive care unit (ICU) admission, ICU
      mortality, and hospital mortality were further examined using multivariate Cox
      regression and multivariate logistic regression analysis. Results: 2 273 qSOFA
      negative patients with sepsis and 3 342 non-sepsis controls were included finally
      with a PSM cohort consisted of 1 677 sepsis patients and 1 677 controls. Results
      of ROC analysis showed that the area under ROC curve was 0.753 [95% confidence
      interval (CI) 0.741-0.765] and the optimal OASIS threshold according to the
      Youden index was 26.5 and yielded a 67.2% sensitivity and 70.8% specificity.
      Multivariate regression analysis indicated that OASIS>26 was an independent risk
      factor for 28-day mortality (hazard ratio 2.80, 95% CI 2.15-3.65, P<0.01), ICU
      mortality (odds ratio 4.69, 95% CI 2.60-8.49, P<0.01), and hospital mortality
      (odds ratio 4.48, 95% CI 3.13-6.42, P<0.01). Analysis of the PSM cohort presented
      consistent results. Conclusions: OASIS had a good discriminative value to
      differentiate qSOFA-negative patients with sepsis from those without sepsis.

PMID- 30196604
TI  - [Effect of connecting airbag in different filling state at the front end of
      piezometric tube in noninvasive ventilation circuit on man-machine
      synchronization].
AB  - Objective: To investigate the effect of connecting airbag in different filling
      state at the front end of piezometric tube in the noninvasive ventilation circuit
      on pressure transmission and human-machine synchronization. Method: In test 1,
      the airbag was connected to a piezometric tube which was placed in a closed
      container, the filling state of the airbag was regulated, and the pressure inside
      the container was changed to observe the corresponding pressure change in the
      piezometric tube. In test 2, the airbag in different filling state was connected
      at the front end of piezometric tube in noninvasive ventilation circuit. Twelve
      subjects were connected to the ventilator such that dynamic changes in the
      pressure inside the mask (Pmask) and piezometric tube (Ptube) could be measured.
      Data with normal distribution was analyzed by t test, while data with abnormal
      distribution was analyzed by K-W test. Results: In test 1, the pressure inside
      the container changed between 0 and 50 cmH(2)O(1 cmH(2)O=0.098 kPa), when the big
      airbag was filled at 1/5, 2/5, 3/5, 4/5, the medium-sized airbag was filled at
      3/5, 4/5, 5/5, and the small airbag was filled at 4/5, the pressure inside the
      piezometric tube changed synchronously with the pressure inside the container
      with no statistically significant difference(P>0.05). In a state of no filling in
      the small airbag and the medium-sized airbag, and filled at 1/5 in the small
      airbag, the pressure inside the piezometric tube no longer changed with the
      pressure in the container when the pressure reached a certain level .When the
      small airbag was filled at 1/5, 2/5, 3/5, 5/5, the medium-sized airbag at 1/5,
      2/5, and the big airbag at 5/5, and all the airbags were in the state of no
      filling , the difference in the pressure between the piezometric tube and the
      container was statistically significant. In test 2, respiratory ventilation
      parameters were set on 10/4 cmH(2)O-30/14 cmH(2)O , and the connecting airbag at
      the front end of piezometric tube in noninvasive ventilation circuit. The
      platform pressure in the mask was slightly higher than that in the piezometer
      tube, and the baseline pressure in the mask was slightly lower than that of the
      piezometer tube. When the big airbag was filled at 1/5, 2/5, 3/5, 4/5 and medium
      sized airbag at 2/5, 3/5, 4/5, the pressure difference between Pmask and Ptube
      was less than 0.5 cmH(2)O, which was acceptable clinically. When the big airbag
      was filled at 1/5, 2/5, 3/5 and the medium-sized airbag at 2/5, 3/5, there was no
      significant difference in trigger work before and after connecting the airbag at
      the front end of the piezometric tube(P>0.05). Conclusion: Connecting the airbag
      at the front end of the piezometric tube could avoid the forming of condensate in
      piezometric tube. The airbag showed good properties of pressure conductivity
      under ideal size and filling state.

PMID- 30196605
TI  - [Analysis of factors associated with failure of sequential mechanical ventilation
      in patients with acute exacerbation of chronic obstructive pulmonary disease
      complicated with respiratory failure].
AB  - Objective: By retrospectively analyzing the clinical data of patients with acute
      exacerbation of chronic obstructive pulmonary disease (AECOPD) complicated with
      respiratory failure, to find the associated factors for failure of invasive
      noninvasive sequential ventilation therapy. Methods: We conducted a cohort study
      of 64 patients with AECOPD complicated with respiratory failure, who were treated
      by invasive-noninvasive sequential ventilation. We took re-intubation, death or
      spontaneous discharge within 7 days following extubation as the endpoints. By
      comparing the APACHE II score at admission into RICU, the ABCD grouping for COPD,
      the ratio of the diameter of the pulmonary artery to the diameter of the
      ascending aorta in chest CT(PA: A ratio), the levels of NT-proBNP, PaCO(2),
      PaO(2), the total number of leukocytes and the level of procalcitonin, we
      analyzed the differences between the success group(43 cases) and the failure
      group(21 cases). Results: The APACHE II score at admission to RICU, the PA: A
      ratio, the level of NT-proBNP, the total leukocytes and the level of
      procalcitonin at admission to RICU showed significant differences in the
      univariate analysis(P<0.05). The average APACHE II score was 23+/-4 in the
      success group and 27+/-6 in the failure group. The average PA: A ratio was 0.88+/
      0.09 in the success group and 1.03+/-0.10 in the failure group. In the
      multivariate regression analysis, there were significant differences only in the
      APACHE II score(P=0.02)and the PA: A ratio(P=0.012). The area under the ROC curve
      of the PA: A ratio for all patients was 0.894 and the cut-off value of the PA: A
      ratio was 0.98. Conclusion: The APACHE II score and the PA: A ratio in CT are
      independent risk factors for failure of sequential ventilation in AECOPD patients
      complicated with respiratory failure. In particular, patients with a PA: A ratio
      greater than 0.98 have a higher risk of treatment failure.

PMID- 30196606
TI  - [The clinic experience of implantable diaphragm pacer in a patient with high
      cervical spinal cord injury and literature review].
AB  - Objective: To report the use of implantable diaphragm pacer (IDP) in a patient
      with high cervical spinal cord injury(HCSCI). Methods: A 14-year-old male
      patient, who suffered from a HCSCI at C2 neurological level and had been on a
      ventilator for 2 years, received IDP in August 2017 at China Rehabilitation
      Research Center. A systematic literature review was performed on IDP in patients
      with HCSCI in Pubmed, CNKI, and Wanfang databases, using the keywords: phrenic
      nerve and electrical stimulation and spinal cord injury; IDP and spinal cord
      injury; breathing pacemaker system and spinal cord injury. All fields were
      covered from 1970/01/01 to 2018/01/01 in Pubmed, from 1981/01/01 to 2018/01/01 in
      CNKI, and from 1900/01/01to 2018/01/01 in Wanfang. Results: No spontaneous
      breathing was observed preoperatively in the patient. The electrical response of
      phrenic nerves was intact on the right, but unresponsive on the left. We got
      started with the IDP at 4 weeks after surgery. The threshold voltage of the right
      hemidiaphragm pacing was 0.1 V and at the level of 0.7 V with an optimal effect.
      No significant diaphragmatic contraction was found at left side with the extent
      up till 0.7 V. The maximum tidal volume was 840 ml when electrical stimulation
      was given at an intensity of 0.7 V bilaterally. The bilateral stimulation voltage
      at 0.1-0.2 V, pacing frequencies at 9 beats/min in bed, or at 12 beats/min on
      wheelchair, were set to maintain the tidal volume at the level of (435+/-32) ml.
      After 2-week adaptive training, the patient could wean from the ventilator for 12
      hours and had a normal blood gas analysis. At 6 week after surgery, with the aid
      of IDP, the patient could get out in wheelchair for outdoor activities. By
      literature review, we found 78 English papers, including 6 clinical trials, 10
      reviews, and 11 Chinese papers, consisting of 8 reviews, 1 study in animal, and 2
      news reports. Extensive contents, such as preoperative evaluation, preoperative
      preparation, surgical procedures, complications, surgical outcomes, and animal
      model studies of IDP were involved. The indications of IDP reported by literature
      were: (1) central alveolar hypoventilation; (2) Sleep apnea syndrome (Biot's
      respiration); (3) Respiratory failure induced by brainstem injury or disease; (4)
      Respiratory failure induced by spinal cord injury or disease above C3 level.
      Conclusion: Our case study confirmed the therapeutic effect of IDP on patients
      with respiratory failure caused by HCSCI.

PMID- 30196607
TI  - [Clinical features of 12 cases of respiratory diseases associated with
      inflammatory bowel diseases].
AB  - Objective: To investigate the clinical features of respiratory diseases
      associated with inflammatory bowel diseases(IBD). Methods: A retrospective
      analysis was performed for 12 cases of respiratory diseases associated with IBD
      admitted to Beijing Chaoyang Hospital from January 2011 to May 2017. Their
      clinical data, including symptoms, laboratory, spirometry, radiological findings
      as well as therapy and clinical course, were collected. Results: These 12
      patients, including 11 males and 6 smokers, were 37-75 years old, with an average
      age of (61+/-12) years. There were 11 patients with ulcerative colitis(UC) and 1
      with Crohn's disease(CD). The interval between the diagnosis of IBD and the
      occurrence of respiratory diseases ranged from 5 months to 30 years. The patients
      did not receive therapy for IBD when respiratory diseases were diagnosed. The
      respiratory diseases associated IBD included bronchiectasis (n=3), interstitial
      lung diseases (n=5, with 2 cases of organizing pneumonia by pathology), pulmonary
      embolism(n=3) and pulmonary arterial stenosis (n=1). Of the 12 cases, 9 presented
      with respiratory symptoms, including cough, expectoration and dyspnea. One
      patient presented with abdominal symptoms and 2 cases were found by physical
      examinations. Chest CT features were manifested as bronchiectasis, reticular
      patterns, patchy opacity and pulmonary artery filling defect. Conclusions:
      Respiratory diseases associated with IBD are various, which can involve airways,
      interstitium and pulmonary vessels. Respiratory diseases seem to be more common
      in patients with UC as compared to those with CD.

PMID- 30196608
TI  - [Analysis of the characteristics of electrocardiogram in patients of different
      genders with pulmonary hypertension].
AB  - Objective: To analyze the characteristics of ECG in patients with pulmonary
      hypertension(PH) and explore their correlation with pulmonary vascular
      resistance(PVR), mean pulmonary arterial hypertension(mPAP) and cardiac
      index(CI). Methods: A total of 186 patients with right heart catheterization were
      enrolled in the Department of Respiratory of the First Affiliated Hospital of
      Guangzhou Medical University from August 2015 to October 2017. Patients with
      normal pulmonary artery pressure, incomplete clinical data and repeated
      examinations were excluded and there were 101 patients with pulmonary
      hypertension included. The results of ECG parameters and right heart
      catheterization were collected to analyze the ECG characteristics of patients
      with different genders and their correlation with PVR, mPAP and CI. Results:
      Among all PH patients, the duration of QRS axial in male group was significantly
      longer than that of the female group [(110.38+/-15.829) vs. (98.63+/-18.041) ms,
      P<0.001], and the S wave amplitude in V5 was significantly higher compared to
      female group [(1.304+/-1.356) vs. (0.648+/-0.663) mv, P<0.001]. Their heart rate
      corrected QT interval (QTc), QRS axis, S wave amplitude in I, S and R wave
      amplitude in V1, R/S ratio in V1, S wave amplitude V5, all had a correlation with
      their PVR and the S wave amplitude in V1 was negatively correlated with PVR (r=
      0.441, P<0.001). In the male group, PVR was not correlated with R/S ratio in V1
      and S wave amplitude in V5. While PVR in the female group was significantly
      correlated with QTc, R wave amplitude in V1, R / S ratio in V1. In all PH
      patients, their P wave duration in II, QRS axis and S wave amplitude in I, S wave
      and R wave amplitude in V1, S wave amplitude in V5, QTc, R/S ratio in V1, all had
      correlations with mPAP (P<0.05). In male group, mPAP was not correlated with QTc,
      P wave duration in II, and the S wave amplitude in V5 (P>0.05). The mPAP in the
      female group was only related to the S wave and R wave amplitude in V1, and S
      amplitude in I and S wave amplitude in V5 (P<0.05). The CI was positively
      correlated with the S wave amplitude in V1 (r=0.34, P<0.001), and negatively
      correlated with the QRS axis (r=-0.219, P=0.04); CI in male group was not
      correlated with QRS axis(P=0.073), but correlated with QTc (r=-0.296, P=0.044).
      Conclusion: There were gender differences in QRS duration and S wave amplitude in
      V5 in patients with pulmonary hypertension. The QRS axis and the S wave amplitude
      in V1 were related to the heart index. There was a difference in the correlation
      between ECG and PVR, mPAP and CI in patients of different genders with pulmonary
      hypertension.

PMID- 30196609
TI  - [The research progress on the function and clinical value of micro RNA in
      sepsis].

PMID- 30196610
TI  - [The potential role and value of Vimentin in sepsis].

PMID- 30196611
TI  - [Application of ultrasonography in the diagnosis of pulmonary embolism].

PMID- 30196612
TI  - [The application of PD-1 antibody in infectious diseases].

PMID- 30196614
TI  - [Considerations of long-term stability of orthodontic treatment results].

PMID- 30196613
TI  - [Advance in assessment instruments of comorbidity in chronic obstructive
      pulmonary and their application].

PMID- 30196615
TI  - [Consensus recommendations from Chinese experts on the standard operation
      procedure of curing light in direct composite resin adhesive restorations].
AB  - The curing light in direct composite resin adhesive restorations is a common
      technique and treatment method in oral clinic. It has many advantages, such as
      matching the color of the teeth, less removing the hard tissues of the teeth,
      resistance to abrasion, good masticatory performance and so on. It has almost
      replaced the traditional amalgam filling in the clinical dentistry repair.
      However, in clinical practice, improper use of the technique can also lead to
      increased loss of restorations and postoperative sensitivity. The reason is
      related not only to the physical and chemical properties of the material itself,
      but also the operator's lack of understanding and mastering the properties of the
      light cured material, especially the use rules of the light curing lamp. To this
      end, in September 2017, the vice chairman of Society of Cariology and
      Endodontology, Chinese Stomatological Association, professor Liang Jingping,
      organized a part of professional experts in this field, and invited the chief
      expert in 3M company, Dr. Joe Oxman, held a meeting about the use principle,
      operation mode and specification symposium of light curing lamp. Experts at the
      meeting had a very heated discussion, forming the following consensus.

PMID- 30196616
TI  - [Stability of orthodontic treatment in the patients with cleft lip and palate].
AB  - Severe maxillary deficiency is often seen in cleft lip and palate patients due to
      multiple factors such as congenital defect, traumatic effect of surgeries and
      constriction of scar tissue, which causes moderate to severe crowding and
      anterior and posterior crossbite. Orthodontic treatment is usually difficult and
      time consuming. Upper arch expansion and maxillary protraction are often carried
      out to release transverse and sagittal intermaxillary discrepancy. Orthodontic
      treatment for cleft patients is different from that of non-cleft patients.
      Special management is needed and the stability of treatment should be considered.
      Relapse usually occurred after upper arch expansion especially in canine and
      premolar area. Over expansion should be cautious and orthognathic surgery may
      reduce the unstability of expansion. Maxillary protraction can improve the facial
      esthetics of the children with cleft. Alveolar bone grafting could improve the
      protraction effect and reduce the side effect such as clockwise mandibular
      rotation and upper incisor proclination. Forward movement of maxilla by
      protration is stable and continuous growth of the mandible is the most liable
      factor causing relapse. High mandibular angle and over growth of mandible are the
      risk factors of unstability of maxillary protraction.

PMID- 30196617
TI  - [A review of the effectiveness and long-term stability of the functional
      appliance].
AB  - The orthopedic treatment of the orthodontics is a typical and crucial technique
      and method that uses functional appliances to fully work out the potentials of
      the jaws and muscles, and accordingly to correct the functional or mild skeletal
      malocclusions in pre-pubertal children and adolescents. A successful orthopedic
      treatment involves its short-time effectiveness and its long-term stability. For
      many years, however, the effectiveness of the functional appliance is
      controversial and the long-term stability of the functional appliance has always
      been overlooked. Thus, with an aim of presenting guidelines on orthopedic
      treatment, the effectiveness and the long-term stability of the functional
      appliance are discussed in this article.

PMID- 30196618
TI  - [Advances in studies on distal molar movement with temporary anchorage devices].
AB  - Crowding and protrusion of the dentition are often the chief complaint of
      orthodontic patients. For patients with severe crowding or protrusion,
      orthodontist often improve their profile with premolar extraction treatment.
      However, for patients with mild crowding and protrusion, orthodontist usually
      achieve treatment objective using distal molar movement with temporary anchorage
      devices (TAD). The present article reviewed the advances in the use of TAD in
      total arch distalization, including therapeutic effect measured in three
      dimensions, factors that affected distal movement and the stability of curative
      effect.

PMID- 30196619
TI  - [Factors affecting stability after fixed orthodontic treatment].
AB  - Objective: To analyze factors affecting stability after fixed orthodontic
      treatment. Methods: Five hundred and forty-four patients who had finished fixed
      orthodontic treatment more than two years in First Department of Orthodontics,
      China Medical University from January, 2000 to December, 2017 were investigated
      and the rate of regular revisit was counted. The data of 288 patients were
      successfully collected by calling or sending text messages and the rate of
      standard use of retainers as prescribed (patients wore retainers for 24 months or
      longer) was counted. According to the variation of peer assessment rating (PAR)
      index at the start of retention and the time the data collected, the patients
      were divided into relapse group (variation of PAR index >5) and non-relapse group
      (variation of PAR index <=5). Difference significance analysis and multiple
      factor logistic regression analysis were used. Sixty patients wearing retainers
      well were collected and the curative effects of Hawley retainer and vacuum formed
      retainer (VFR) were compared, which included overbite, overjet, maxillary
      irregularity index, mandibular irregularity index, width betwenn canine and width
      between first molar. Results: The rate of regular revisit was 41.0% (223/544).
      Two hundred and one of 288 patients (69.8%) who were visited successfully had
      regular revisit, and 60.4%(174/288) of the patients wore retainers well; 30.2%
      (87/288) of the patients who were visited successfully didn't have regular
      revisit, and 10.4% (30/288) of the patients wore retainers well. Difference
      significance analysis showed that there was highly significant difference between
      relapse group and non-relapse group in the type of retainer and duration of
      retention (P<0.01). One hundred and forty of 224 patients (62.5%) in non-relapse
      group and 37.5% (24/64) of the patients in relapse group used VFR, and the
      duration of retention in non-relapse group was significantly longer than that in
      relapse group (P<0.01). Multiple-factor Logistic regression analysis showed that
      wearing Hawley retainers (OR=3.067, P<0.05) was the risk factor influencing
      relapse. The duration of retention (OR=0.832, P<0.01) was the protective factor
      influencing relapse. Independent-sample t test indicated that the variations of
      maxillary [(0.82+/-0.36) mm] and mandibular [(1.05+/-0.22) mm] irregularity index
      in Hawley retainer group were larger than maxillary [(0.64+/-0.29) mm] and
      mandibular [(0.72+/-0.35) mm)] irregularity index in VFR group, respectively. The
      differences between the two groups were significant (P<0.05). Conclusions:
      Duration of retention was implicated in stability after orthodontic treatment.
      VFR had better effect in the aspects of irregularity index than Hawley retainer.

PMID- 30196620
TI  - [Orthodontic treatment of a patient with unilateral complete cleft lip and
      palate].

PMID- 30196621
TI  - [Fifteen-year follow-up of a skeletal class III patient after orthodontic
      treatment with extraction of four premolars].

PMID- 30196622
TI  - [Long-term follow-up of an orthodontically treated class II patient with
      crowding].

PMID- 30196623
TI  - [Long-term follow-up of an adult skeletal class III patient after orthodontic
      treatment].

PMID- 30196624
TI  - [Maxillary protraction treatment of a skeletal class III patient with severe
      maxillary crowding].

PMID- 30196625
TI  - [Long-term stability of a functional class III patient with severe crowding after
      nonsurgical orthodontic treatment].

PMID- 30196626
TI  - [Economic evaluation of treatments under dental general anesthesia and protective
      stabilization].
AB  - Objective: To conduct economic evaluation of treatments under dental general
      anesthesia (DGA) and protective stabilization (PS), in order to compare the cost
      and the final therapeutic effect of these two treatments. Methods:
      Retrospectively studied twenty-six 2 to 4 years old patients treated under DGA
      and twenty-seven treated under PS in the Department of Pediatric Dentistry,
      Peking University School and Hospital of Stomatology. The general information,
      treatment information and total treatment cost information of patients were
      collected. The cost and cost-survival time ratio of the two groups were compared
      in units of people and tooth respectively. When compared in unit of people,
      patients were divided into two groups depending on the number of teeth treated,
      when compared in unit of tooth, teeth were divided into two groups depending on
      the treatment received, i.e. restoration or root canal treatment. In addition, we
      recalculated and compared two groups under the assumption that the treatment
      charges of DGA was consistent with common outpatient charges. Results: The tooth
      average cost and cost-survival time ratio of each patient in DGA group which were
      [(1 133.87+/-87.37) yuan] and [3.51 (1.30, 5.72) yuan/d] respectively were
      significantly higher than those in PS group which were [(303.81+/-155.34) yuan]
      and [1.54 (0.95, 2.13) yuan/d] respectively (P<0.01). The number of teeth and the
      way of treatments wouldn't change the result. The recalculated result of the cost
      survival time ratio of each patient in DGA group [1.63 (0.72, 2.55) yuan/d] and
      PS group [1.54 (0.95, 2.13) yuan/d] showed no significant difference (P=0.455).
      Conclusions: Patients treated in Peking University School and Hospital of
      Stomatology showed a significant higher cost and cost-survival time radio in DGA
      group than that in PS group. If the treatment charges of DGA group was consistent
      with common outpatient charges, PS group will no longer have economic advantage.

PMID- 30196627
TI  - [Expression profile of long non-coding RNA in gingival tissues from the patients
      with aggressive periodontitis].
AB  - Objective: To detect and analyze the differential expression profile of long non
      coding RNA (lncRNA) in aggressive periodontitis (AgP) and healthy gingival
      tissues, in order to explore the role of lncRNA in AgP. Methods: After the
      informed consents were obtained, gingival tissues from AgP patients (n=40) and
      healthy volunteers (n=40) were collected in Department of Periodontology, Ninth
      People's Hospital, Shanghai Jiao Tong University School of Medicine (from Mar.
      2012 to Aug. 2012) and Department of Periodontology, Hospital of Stomatology,
      Tianjin Medical University (from Oct. 2016 to Apr. 2017). The differential
      expression of lncRNA of tissues from AgP patients (n=20) and healthy volunteers
      (n=20) were examined via microarray assay. Bioinformatics was applied to analyze
      the expression data of lncRNA and correlative mRNA. Two lncRNAs (lncRNA-TNFRSF13C
      and lncRNA-API5) were chosen to verify the microarray results by using real time
      quantitative polymerase chain reaction (PCR) in the other gingival tissues.
      Results: Compared with the result of healthy gingival tissues, totally 8 632
      lncRNAs were differentially expressed in tissues from AgP patients. From these
      data, 1 986 lncRNAs were significantly upregulated while 6 646 lncRNAs were
      downregulated, amongst which 48 lncRNAs were upregulated (>10 times) (P<0.05), 14
      lncRNAs were downregulated (>10 times) (P<0.05). Furthermore, totally 5 519
      correlative mRNAs were differentially expressed, amongst which 1 676 mRNAs were
      upregulated (>=2 times, P<0.05) and 3 843 mRNAs were downregulated<=0.5 (P<0.05).
      The selected lncRNA-TNFRSF13C and lncRNA-API5 were up-regulated in AgP (P<0.05),
      which confirmed the results of microarray. From bioinformatics, differential
      expression lncRNAs were in association with many signal pathways including toll
      like receptor signaling pathway, cell cycle and apoptosis pathway, and tumor
      necrosis factor receptor superfamily pathway. Conclusions: LncRNA may be involved
      in the pathogenesis of AgP through various pathways, which need to be further
      explored.

PMID- 30196628
TI  - [Effect of human trophoblast cell-surface antigen 2 gene expression by RNA
      interference on proliferation and apoptosis of tongue squamous cell carcinoma and
      its mechanism].
AB  - Objective: To investigate the effect and its mechanism of human trophoblast cell
      surface antigen 2 (Trop2) gene expression was inhibited in squamous cell
      carcinoma of tongue on the proliferation and apoptosis of cancer cells. Methods:
      A total of 46 patients from February 2014 to May 2016 received radical treatment
      of tongue cancer from oral and maxillofacial surgery of the First Affiliated
      Hospital of Zhengzhou University were enrolled in this study. Real time PCR and
      Western blotting were used to detect mRNA and protein expression of Trop2 in
      tongue squamous cell carcinoma and corresponding adjacent tissues; NC-siRNA and
      Trop2-siRNA were transfected into human tongue squamous cell carcinoma CAL-27
      cells, a blank control group (control) was set, the expression of Trop2, Ki-67,
      cyclin D1, cleaved caspase3, Notch1, Hes1 protein after transfected for 48 h were
      detected by Western bloting; cell proliferation was detected by cell counting kit
      8; cell cycle and apoptosis rate were detected by flow cytometry. Results: The
      mRNA (5.72+/-1.13) and protein expression (0.77+/-0.06) of Trop2 gene in tongue
      squamous cell carcinoma were significantly higher than those in adjacent tissues
      (0.92+/-0.15, 0.11+/-0.01, P<0.05); Trop2 protein expression after transfeced
      Trop2-siRNA (0.08+/-0.01) in CAL-27 cells decreased significantly (0.46+/-0.05);
      the survival rate (64.28+/-4.12)%, S cells (14.54+/-1.02)% and Ki-67 (0.12+/
      0.01), cyclin D1 (0.04+/-0.01) protein expression in Trop2-siRNA group were
      significantly lower than those in control group [(100.00+/-1.02)%, (27.33+/
      1.11)%, (0.24+/-0.02), (0.20+/-0.02)] and NC-siRNA group [(96.55+/-2.43)%,
      (26.67+/-1.23)%, (0.26+/-0.03), (0.21+/-0.024)], the apoptosis rate (23.55+/
      1.45)%, G0/G1 cells (72.32+/-0.94)% and the expression of cleaved caspase 3
      (0.16+/-0.02), Notch1 (0.62+/-0.06) and Hes1 (0.50+/-0.05) protein were
      significantly higher than control group and NC-siRNA group (P<0.05). Conclusions:
      The expression of Trop2 gene was inhibited in tongue squamous carcinoma cells can
      reduce the proliferation of cancer cells, block the cells in phase G1, and
      promote the apoptosis of cells. The mechanism is related to the up regulation of
      Notch1 signaling pathway.

PMID- 30196629
TI  - [Clinical applications of transcrestal around detached sinus floor elevation
      technique using osteotomes and sequential drills with stops].
AB  - Sinus floor elevation was needed in 11 patients having 15 implant sites with the
      residual bone height (RBH) was less than 10 mm in the posterior maxillary region
      from Feb to May 2017. The RBH ranged from 3.10 to 8.34 mm [averaged (6.18+/-1.60)
      mm]. RBH<6 mm was observed in 40% implant sites (6 implant sites) and RBH>=6 mm
      was observed in 60% implant sites (9 implant sites). The thickness of the sinus
      floor membrane correspond to the implant site measured by cone beam CT (CBCT)
      ranged from 0.50 to 4.24 mm [averaged (1.21+/-0.92) mm]. Sequential drills with
      stops were used to perforate the cortical bone of the sinus floor firstly, then
      the transcrestal around detached sinus floor elevation technique (TADSFET) was
      carried with osteotomes. Anorganic bovine bone was used as the augmentation
      material.Fifteen implants were placed in 15 implant sites. CBCT pictures showed
      that there was a smooth and continuous tent-shaped apophysis on each lifted site
      and no air fluid level was observed in the sinus immediately after operation. The
      mean elevated height of the 15 implant sites was (7.83+/-1.57) mm (ranged from
      5.94 to 11.01 mm). The mean follow-up time was 7.91 months (7-10 months). The
      survival rate was 100% during the follow up period.

PMID- 30196630
TI  - [Thoughts of international cooperation programs of HIV/AIDS in China].

PMID- 30196631
TI  - [Drinking water safety: the basis of "Healthy China 2030" blueprint].

PMID- 30196632
TI  - [Recommendations on use of human papillomavirus vaccines in adult women].

PMID- 30196633
TI  - [Exposure to disinfection by-products during gestation and newborns' small for
      gestational age].
AB  - Objective: To explore the associations between exposure to chlorination
      disinfection by-products (CDBPs) during gestation and newborns' small for
      gestational age (SGA). Methods: During April 2010 to July 2012, a total of 3 903
      pregnant women who lived in a district with the same water treatment plant in
      Wuhan, China were recruited to this perspective study. Information about
      demographic characteristics of pregnant women and their newborns was collected.
      The tap water samples were monthly collected for 28 months in 3 different sites,
      with 84 samples, and 4 kinds of trihalomethanes (THMs)(chloroform (TCM),
      bromodichloromethane (BDCM), dibromochloromethane (DBCM), and bromoform (TBM))
      and 2 kinds of chlorohaloacetic acids (HAAs) (trichloroacetic acid (TCAA),
      dichloroacetic acid (DCAA)) were determined. The pregnant women were divided into
      4 groups(Q1 to Q4) by quartile method according to their exposure level of CDBPs.
      Binary Logistic regression models were used to assess the associations between
      exposure to CDBPs during gestation and newborns' small for gestational age.
      Results: The average weight of all the newborns was (3 310.19+/-389.91) g, of
      which 169 (4.33%) were SGA. The median concentrations of TCM, BDCM, bromo-THMs,
      total THMs, TCAA, and DCAA during the whole pregnancy were 18.07, 4.93, 8.51,
      26.74, 10.65, and 13.77 MUg/L, respectively. Binary Logistic regression analysis
      showed dose-response relationships between elevated TCM and total THMs during the
      whole gestation and compared with Q1 group, while there was a increased risk of
      SGA in Q4 group, and OR(95%CI) was 1.87 (1.01-3.49) , 2.30 (1.22-4.35) ,
      respectively (P for trend equaled to 0.044, 0.015). Compare with Q1 group, there
      also be positive associations between exposure to TCAA (Q4 group) during first
      trimester and the whole gestation and SGA, while OR(95%CI) was 2.16 (1.19-3.91)
      (P for trend equaled to 0.015). Conclusion: Exposure to CDBPs during gestation
      might increase the risk of newborns' SGA.

PMID- 30196634
TI  - [Study on the transfer mechanism and destructive law of the bacterial antibiotic
      resistance genes disinfected by chlorination].
AB  - Objective: To study the response of Escherichia coli (E. coli) HB101 (plasmid
      pUC19) and its carried antibiotic resistance genes to the process of
      cholorination under different environmental conditions. Methods: The E. coli
      strain was reacted with sodium hypochlorite at the concentration of 0.5, 0.75,
      1.00, and 0.55 mg/L, then the residual chlorine and the colonies were detected at
      the 0.25, 1, 2, 5, 10, 20, and 30 min of the reaction, respectively. The first
      order disinfection kinetic model and EFH model were used to evaluate the
      inactivation effect of E. coli (plasmid pUC19) treated by sodium hypochlorite,
      while the plasmid pUC19 and antibiotic resistance gene amp(r) were detected by
      PCR method. Besides, the logarithm of Ct (residual chlorine in t) under different
      concentration were calculated. Results: The temperature and pH value played
      important roles on the inactivation of E. coli and elimination of plasmid pUC19
      and amp(r) under the function of sodium hypochlorite. The Ct value needed for 5
      log of E.coli HB101(pUC19) inactivation at 4, 20, 36 C was 11.92, 10.28, 7.67,
      respectively, and when the pH was in 6.0, 7.0, 8.0, with chloride concentration
      were 0.75, 0.70, 0.55 mg/L, the Ct value needed for reached to 6.68, 10.28, 15.73
      min.mg/L. At pH 7.2 condition, when the temperature was 4, 20, 36 C, and chloride
      concentration were 9, 5, 3 mg/L.The required Ct values to completely destroy the
      transformation function of free antibiotic resistant plasmids were 36.11,
      34.17,16.09 min.mg/L. Sodium hypochlorite disinfection can release free ampr gene
      and even the transformed plasmid pUC19, and pollute the water body. Only when the
      Ct value reached 903.03 min.mg/L, the complete ampr gene can be destroyed which
      was far more exceed the bacterial lethal Ct value. Conclusion: Even if all the
      antibiotic resistant bacteria were inactivated, the antibiotic resistant plasmids
      or genes might still maintain complete with the transformable function, which may
      result in new potential risks of waterborne diseases.

PMID- 30196635
TI  - [The transformation of microcystin-LR during tap water treatment process and
      analysis of its degradation products].
AB  - Objective: To establish a liquid chromatography-tandem mass spectrometry
      (LC/MS/MS) method for the determination of microcystin-LR (MC-LR) in drinking
      water, investigate its removal efficiency during tap water advanced treatment
      process and analyze its degradation products in the tap water. Methods: Two
      parallel water samples were collected from each point of tap water advanced
      treatment process in September 2015, November 2015 and January 2016,
      respectively, and treated by mixing, filtration, concentration, elution, nitrogen
      blow and re-dissolvement. The samples were analyzed by LC/MS/MS to determine the
      MC-LR concentration and its removal efficiency during treatment process. The
      combination of actual water enrichment (including source water enrichment of 50
      times and 1 500 times concentrated, finished water enrichment of 50 times and 2
      500 times concentrated) and laboratory simulated water (including the mixture of
      MC-LR and liquid chlorine in the mass ratio of 1?10, 1?20, 1?100 and 1?1 000,
      respectively) were used to qualitative analyze the MC-LR degradation products by
      Orbitrap mass spectrometry. Results: The linearity of MC-LR ranged from 2 to 200
      MUg/L with the detection limit of 0.007 9 MUg/L and the limit of quantification
      of 0.026 3 MUg/L. The recovery rate of MC-LR from different contration in
      drinking water were from 94.88%-101.47%. The intra-day precision was 2.51%-7.93%
      and the intra-day precision was 3.24%-8.41%. The average concentration of MC-LR
      in source water was (0.631+/-0.262) MUg/L, 94.0% of which can be removed by ozone
      exposure while the concentrate was (0.038+/-0.016) MUg/L, biological pre
      treatment and chlorination. The remaining can hardly be removed by sand
      filtration, ozone exposure, activated carbon, ultrafiltration and other
      processes. The MC-LR average concentration in the finished water maintained at
      about (0.036+/-0.016) MUg/L. Degradation products including hydroxy-microcystin,
      methyl-hydroxy-microcystin, methyl-microcystin were identified in the laboratory
      simulated water of the mixture of MC-LR and liquid chlorine in the mass ratio of
      1?10. Conclusion: The established MC-LR detection method can be well applied to
      the monitoring of MC-LR in drinking water due to its simple pre-treatment process
      and good methodological validation parameters. The degradation products of
      treatment processes was different.

PMID- 30196636
TI  - [Time-series analysis of association between ambient ozone and premature birth in
      Taiyuan, 2013-2015].
AB  - Objective: To understand the correlation between ambient ozone (O(3)) and
      premature birth in Taiyuan. Methods: The data of O(3) daily average
      concentrations and maximum concentration of 8 hours, PM(2.5) daily average
      concentrations, meteorological factors (including the average temperature and
      relative humidity) and daily premature birth numbers during 2013-2015 were
      collected in Taiyuan from China National Environmental Monitoring Center and
      China Meteorological Administration. The models were developed by using
      generalized linear model. The gender of the premature birth was analyzed by
      subgroup analysis. Sensitive analysis were used to estimate the model stability.
      Results: Ambient O(3) daily average concentrations and maximum concentration of 8
      hours in Taiyuan of 2013 to 2015 were 45.35 MUg/m(3) and 71.33 MUg/m(3)
      respectively. In single pollutant model, the effects of different window
      exposures on premature birth were different. The RR of preterm birth about an
      increase of 10 MUg/m(3) of O(3) (lag 3 weeks, lag 4 weeks) were 1.090 (95%CI:
      1.042-1.139), 1.095 (95%CI: 1.032-1.163) respectively. According to the infant
      gender subgroup analysis, male infants were more likely to be affected by ambient
      O(3). The average daily of O(3) concentration increased by 10 MUg/m(3), and the
      RR for male infants and female infant were 1.013 (95%CI: 0.997-1.029), 0.996
      (95%CI: 0.983-1.010) respectively. By comparing the daily average concentration
      of O(3) with the maximum daily concentration of O(3) for 8 hours as an indicator
      of exposure, it was found that the daily average concentration of O(3) was more
      sensitive. The RR of preterm birth about an increase of 10 MUg/m(3) of average
      daily of O(3) concentration and the maximum daily concentration of O(3) for 8
      hours. were 1.006 (95%CI: 0.994-1.017) and 0.997 (95%CI: 0.988-1.005)
      respectively. As for sensitive analysis, when O(3) introduced PM(2.5) or change
      the degree of model variables, the association of premature birth was still
      constant. Conclusion: Prenatal exposure to O(3) may increase the risk of
      premature birth, with different window exposures premature births have different
      risks and this risk is more pronounced in male infants.

PMID- 30196637
TI  - [Risk assessment of dioxin in the surrounding area of a waste incineration plant
      in Beijing].
AB  - Objective: Assess the health risks faced by local residents, based on the results
      of dioxin detection in the surrounding area of a waste incineration plant in
      Beijing. Methods: Select three representative points plant near the waste
      incineration plant--the people's government, Central Primary School and a
      community, collect 4 air and soil samples and detect their dioxin concentrations
      from March to December 2016, respectively, simulate people's intake through
      breathing, skin contact and soil intake, assess residents' lifetime cancer risk
      according to epidemiological studies. Results: The daily average concentration in
      air at three test points were 0.15, 0.17, 0.19 pg/m(3), and 12.5, 20.2, 6.1 ng/kg
      in soil. At three representative sites, residents' lifetime cancer risk through
      breathing from 9.55*10(-6), 1.08*10(-5), 1.21*10(-5) in the people's government,
      Central Primary School and a community, while through skin contact were 3.40*10(
      7), 5.50*10(-7), 1.65*10(-7), respectively. The lifetime cancer risk through soil
      intake range from 2.08*10(-6) to 6.91*10(-6). The lifetime cancer risk of eating
      vegetables ranges from 5.50*10(-6) to 6.98*10(-6). The lifetime cancer risk of
      eating chicken or eggs ranges from 2.72 *10(-9) to 6.30*10(-9). Residents'
      lifetime cancer risk through soil intake, eating vegetables and eating chicken or
      eggs ranges from 2.08*10(-6) to 6.30*10(-9). Conclusion: Under all exposures, the
      life time risk of cancer for residents around the waste incineration is under the
      upper end of the range of acceptability(10(-4)).

PMID- 30196638
TI  - [Relationship between weight change and the changes in blood pressure, blood
      glucose and blood lipid profiles in middle-aged and elderly Chinese people: a
      cohort study].
AB  - Objective: To explore the relationship between weight change and the changes in
      blood pressure, blood glucose and blood lipid profiles in middle-aged and elderly
      Chinese people. Methods: All participants were from the Dongfeng-Tongji cohort
      study. The study included 16 606 middle-aged and elderly Chinese people with
      complete information in the baseline survey in 2008 and the first follow-up
      survey in 2013. We collected the data on demographic characteristics, lifestyle,
      history of diseases and medication, and the results of medical health
      examinations, including height, weight, blood pressure, fasting blood glucose and
      lipid profiles. We divided the weight change into five groups, moderate or above
      weight loss (<-8.0%), slight weight loss (-8.0%, -3.1%), weight maintenance (
      3.0%, 3.0%), slight weight increased (3.1%, 8.0%), and moderate or above weight
      increased (>8.0%). Generalized linear regression model was used to analyze the
      relationship between weight change and the changes in systolic blood pressure
      (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), total
      cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high density
      lipoprotein cholesterol (HDL-C) and triglyceride (TG). Subgroup analyses were
      used to explore the influences of gender, age and baseline BMI level on the
      relationship between weight change and the above-mentioned metabolic indicators.
      Results: The average age of participants in baseline survey was (62.19+/-7.28)
      years with a range of 45 to 89 years. During the five-year period, there were
      18.86% (2 633), 28.03% (4 655), 35.87% (5 956), 13.96% (2 319), 6.28% (1 043)
      people with moderate or above weight loss, slight weight loss, weight
      maintenance, slight weight increased, and moderate or above weight increased,
      respectively. Regression analyses showed that body weight change were positively
      correlated with changes in SBP, DBP, FBG, TC, LDL-C and TG, and negatively
      correlated with change in HDL-C (all linear trend P values were<0.05); As every
      10% of weight changed, the beta (95%CI) of changes in SBP (mmHg) (1 mmHg=0.133
      kPa), DBP (mmHg), FBG (mmol/L), TC (mmol/L), LDL-C (mmol/L), HDL-C (mmol/L) and
      TG (mmol/L) were 4.94 (4.32, 5.55), 2.50 (2.11, 2.88), 0.05 (0.02, 0.08), 0.13
      (0.11, 0.16), 0.14 (0.12, 0.16), -0.05 (-0.07, -0.04) and 0.16 (0.14, 0.18),
      respectively. Furthermore, subgroup analyses showed that weight change can lead
      to greater changes in blood pressure in older and overweight or obesity elderly
      people (all P for interaction<0.05). Conclusion: Weight loss was beneficial for
      middle-aged and elderly people to improve the blood pressure, blood glucose and
      blood lipid profiles, regardless of the weight at the baseline, while weight gain
      was not.

PMID- 30196639
TI  - [Association between TV watching time and the cognitive functions among the
      elderly aged 60 years and above in Xiamen City].
AB  - Objective: To explore the cognitive functions of the elderly aged 60 years and
      above in Xiamen, and whether TV watching time would affect those functions.
      Methods: We conducted a cross-sectional study on 3 230 registered individuals
      aged 60 years and above in Xiamen from July to October in 2016 with a multi-stage
      random sampling method. Montreal Cognitive Assessment (MoCA) was used to measure
      cognitive functions and ordinal logistic regression was used to quantify their
      associations with TV watching time. Results: A total of 2 944 respondents were
      included in this study. The overall age of them was (70.14+/-7.81) years. 51.49%
      (n=1 516) of all participants were men. Overall, the mean scores of MoCA in
      general and each subdomain cognitive function were 18.65+/-6.43 (general), 5.43+/
      1.17 (orientation), 2.33+/-1.95 (memory), 1.80+/-1.52 (visuospatial), 1.66+/-1.20
      (executive), 4.54+/-1.71 (attention), and 4.09+/-1.64 (language). Compared to
      those who watched TV no more than 2 hours per day, the elderly who did not watch
      TV had a worse performance in general, orientation, memory, visuospatial,
      executive, attention, language function, with OR (95%CI) values about 0.50 (0.35
      0.71), 0.52 (0.37-0.73), 0.68 (0.48-0.96), 0.67 (0.47-0.96), 0.48 (0.34-0.67),
      0.56 (0.41-0.77) and 0.45 (0.33-0.62), respectively. As to respondents who
      watched TV more than 2 hours but no more than 4 hours per day, they had a better
      performance in general, executive, attention, language, and orientation function
      with respective OR (95%CI) values about 1.24 (1.05-1.47), 1.20 (1.02-1.41), 1.41
      (1.19-1.67), 1.51 (1.28-1.77) and 1.33 (1.08-1.64). Conclusion: The elderly aged
      60 years and above in Xiamen City with TV watching time between 2 and 4 hours per
      day had a good performance in cognitive functions compared to those with more or
      less TV watching time.

PMID- 30196640
TI  - [Case-control study on the influencing factors related to cognitive impairment in
      the elderly population of China].
AB  - Objective: To explore the influencing factors affecting the cognitive impairment
      of the elderly population in China. Methods: A stratified multi-stage cluster
      sampling was used in 6 provinces (autonomous administrative regions and
      municipalities) to select the sample. A total 24 000 urban and rural residents
      aged 60 years and above received a set of standardized questionnaire interview,
      physical examinations, laboratory test of lipid and glucose levels of blood and
      apolipoprotein E (APOE) genotype. The primary screening of cognitive function was
      assessed by using the Chinese Version of Ascertain Dementia 8, and then
      suspicious cognitive impairment cases with more than two abnormal results would
      receive the further cognitive function assessment by using the Mini-Mental State
      Examination (MMSE). 1 300 cases with cognitive impairment and 2 600 controls
      without cognitive impairment were recruited and matched according to their age,
      gender and resident area in a 1?2 case-control study. The conditional logistic
      regression model was used to analyze the association between relevant factors and
      cognitive impairment. Results: Factors negatively associated with cognitive
      impairment and their OR (95%CI) values were primary or middle school as 0.63
      (0.51-0.77), high school and above as 0.59 (0.39-0.88), daily neighborhood
      communication as 0.61 (0.50-0.75), weekly participating in social activities 0.59
      (0.44-0.79), daily tea drinking as 0.71 (0.58-0.88) and doing regular exercise as
      0.71 (0.57-0.88), reading newspaper (occasional: 0.50 (0.37-0.67); frequent: 0.40
      (0.28-0.57)), playing majiang or cards (occasional: 0.51 (0.34-0.74); frequent:
      0.50 (0.36-0.68)) respectively. Factors positively associated with cognitive
      impairment and their OR (95%CI) values were APOE-epsilon4 heterozygote as 1.31
      (1.08-1.58), homozygote as 2.74 (1.52-5.00), diabetes onset before 50 years of
      age and after as 9.03 (3.07-33.60) and 4.40 (3.18-6.17), stroke as 1.90 (1.35
      2.69), asthma as 1.95 (1.11-3.42) respectively. Conclusion: APOE-epsilon4
      alleles, lower educational level, stroke, asthma, diabetes are risk factors of
      cognitive impairment in the elderly. Keeping a healthy lifestyle and preventing
      chronic diseases in the whole life course could significantly reduce the
      incidence of cognitive impairment in the elderly.

PMID- 30196641
TI  - [Investigation of drug resistance and multilocus sequence typing for
      differentiation of strains of Candida tropicalis of Shanghai].
AB  - Objective: To analyze the drug resistance of clinical isolates of Candida
      tropicalis in patients with infectious diseases, and preliminarily study their
      molecular characteristics. Methods: 95 strains of Candida tropicalis were
      isolated from the fungal culture specimens of 87 patients with infectious
      diseases in Shanghai Public Health Clinical Center from 2012 to 2015. Meanwhile,
      basic clinical data of patients were collected. The drug resistance of the
      strains to fungal drugs was analyzed by ATB FUNGUS 3 drug sensitivity test
      strips. All strains were classified by Multilocus sequence typing(MLST). Then,
      homology analysis was conducted by MEGA 5.2 software, and the evolutionary tree
      was mapped by using UPGMA method. Results: Patients distribution of strains was
      rendered as following: 31 strains from TB patients, 21 strains from HIV/AIDS
      patients, 19 strains from patients with liver disease, and 24 strains from rare
      cause infection or fever patients. The drug resistance rate to five antifungal
      drugs commonly used in clinical (amphotericin B, 5-fluorine cytosine,
      fluconazole, itraconazole, voriconazole) were 2.11% (2 strains), 0, 26.32% (25
      strains), 26.32% (25 strains), and 26.32% (25 strains) respectively. Among the 25
      azole-resistant strains: 14 strains were from rare cause infection or fever
      patients, 8 strains were from HIV/AIDS patients, and 3 strains were from
      tuberculosis patients. In MLST, 72 sequence types (ST types) were produced, 70 of
      which were new types. Evolutionary tree analysis showed that 95 strains of
      clinical strains distribute as three large clusters. 24 azole resistant strains
      (96.0%) were located in CLUSER I. Conclusion: The isolated Candida tropicalis
      were mainly resistant to azole drugs. MLST typing indicates that they was closely
      related to their genetic background.

PMID- 30196642
TI  - [Etiological study of diarrhea in children under 5 years old in Dongcheng
      district of Beijing].
AB  - Objective: To analyze the etiological characteristics of infectious diarrhea
      among people under 5 years old in Dongcheng District, Beijing. Methods: The age,
      time of infection, clinical symptoms and laboratory test results of the cases who
      didn't used antibiotics within 3 days in the second maternal and child health
      care hospital were collected from 2012 to 2015, through the information
      management system of infectious disease monitoring technology platform. To
      compare the detection rate of virus and bacteria in children with different sex,
      time and age,and the difference of clinical characteristics between virus
      detection group and bacteria detection group by chi square test. Results: 1 977
      cases of infectious diarrhea were collected, the median of the month age (P(25),
      P(75)) was 14.19 (8.31, 23.15) months. The virus detection rate was 34.3% (679
      cases); the bacterial detection rate was 14.6% (288 cases). The difference of
      virus detection rate in children with different months was statistically
      significant (chi(2)=72.38, P<0.001), the virus detection rate of 24-60 months
      (40.9% (188/460)) was the hightest, and the detection rate of 0-5 months (15.3%
      (48/314)) was the lowest. The difference of bacteria detection rate was also
      statistically significant (chi(2)=32.67, P<0.001), and the detection rate of 12
      17 months (19.0% (81/426)) was the highest, the detection rate of 0-5 months
      (6.7% (21/314)) was the lowest. The proportion of vomit and water sample in the
      virus detection group was 22.2% (136 cases) and 73.3% (449 cases), respectively,
      which were higher than those in bacteria detection group (8.1% (18 cases) and
      57.2% (127 cases)), the difference was statistically significant (chi(2) values
      were 125.92 and 19.60; P values were both<0.001); the proportion of mucus stool
      and fever was 0.8% (5 cases) and 14.0% (86 cases), respectively, which were lower
      than those in bacterial detection group (4.1% (9 cases) and 18.5% (41 cases)),
      and the difference was statistically significant (chi(2) values were 8.50 and
      23.01; P values were 0.004 and <0.001). Conclusion: The virus detection rate of
      infantile infective diarrhea is higher than that of bacteria in Dongcheng
      district of Beijing, and the clinical characteristics are significantly
      different.

PMID- 30196643
TI  - [The clinical performance of high risk HPV DNA test among triage women with
      cytology showing atypical squamous cells of undetermined significance].
AB  - Objective: To evaluate the performance of high risk human papillomavirus (HR-HPV)
      DNA test for triage ASC-US in Chinese population. Methods: The study population
      was from Jiyuan city in Henan Province where a cervical cancer screening cohort
      (4 026 women) was set up from April to July in 2017. Women with ASC-US and
      complete recall information of colposcope were selected as the study objects.
      Self-designed questionnaire was used to survey the general information and
      medical history of cervical cancer, thencervical cytological speciments were
      collected for cytodiagnosis and HPV DNA test, followed by colposcopy, lesion
      biopsy and histology diagnose. The diagnosis of histology was used as the gold
      standard. The sensitivity, specificity, positive predictive value (PPV) and
      negative predictive value (NPV) as well as corresponding 95% confidential
      interval (CI) were calculated. Results: The average age of the included 393 women
      with ASC-US were (50.81+/-9.22) years old. The positivity of high risk human
      papillomavirus (HR-HPV), HPV16 and HPV18 were 35.6%, 10.69% and 2.80%,
      respectively. The sensitivity, specificity, PPV and NPV for HR-HPV to detect
      CIN2+ were 84.38% (68.25%-93.14%), 68.70% (63.74%-73.26%), 19.29% (13.61%-26.61%)
      and 98.02% (95.46%-99.15%). When compared with HR-HPV, HPV16/18 had a lower
      sensitivity (59.38% (42.26%-74.48%)) and a higher specificity(91.14% (87.75%
      93.65%)), the PPV and NPV were 59.38% (25.32%-50.98%) and 91.14% (93.61%-97.77%).
      Conclusion: It was more effective for HR-HPV to triage ASC-US than HPV16/18. In
      order to improve the effect of HPV16/18, it should include more HR-HPV types
      which were more prevalent in Chinese population.

PMID- 30196644
TI  - [Screening different HPV genotypes infection and type-specific in cervical
      exfoliated cells of women in Yili area of Xinjiang Uygur Autonomous Region,
      China].
AB  - Objective: To investigate the infection status and genotype distribution of
      cervical human papillomavirus (HPV) in women of different ethnic groups and
      different ages in Yili, Xinjiang Uygur Autonomous Region (Xinjiang). Methods: By
      using the convenient sampling method, 54 760 women from November 2015 to May 2017
      seeking for service in gynecological clinics in a general hospital in Yili,
      Xinjiang, were selected as the research subjects, and 3 445 samples of cervical
      mucous exfoliative cells were collected, and the social information of their
      ethnic and age was collected at the same time. The inclusion criteria were those
      with sexual life, cervical integrity, and ethnic groups for Han or Uygur or
      Kazak. PCR-reverse dot blot hybridization was used to detect HPV genotyping in
      exfoliated cells, and chi-square test was used to compare the difference of HPV
      positive rate among different ethnic groups. Then, according to ethnicity and
      age, the differences in positive rates of different ages and ethnic groups were
      compared in each layer. Results: The positive rate of HPV was 25.6% (882 cases),
      of which the Han, Uygur and Kazakh were 27.9% (564 cases), 22.9% (196 cases) and
      21.6% (122 cases), and the difference was statistically significant
      (chi(2)=13.80, P=0.001). The most prevalent high-risk genotypes of Han women were
      HPV16/52/58, accounting for 24.8% (140 cases), 17.7% (100 cases) and 9.8% (55
      cases), respectively. The most prevalent high-risk genotypes of Uygur women were
      HPV16/52/53, accounting for 34.2% (67 cases), 12.8% (25 cases), 9.2% (18 cases),
      respectively. The most prevalent high-risk genotypes of Kazak were HPV16/52/53,
      accounting for 37.7% (46 cases), 17.2% (21 cases), 12.3% (15 cases),
      respectively. The highest rate of HPV in Uygur patients aged >=61 years was 41.5%
      (22 cases), and the lowest in group 36-40 years old, 15.9% (21 cases), the
      difference between different age groups was statistically significant
      (chi(2)=35.01, P<0.001). Conclusion: The positive rate of HPV infection among
      Han, Uygur and Kazak in Yili Prefecture of Xinjiang was different, and the HPV
      positive genotype differs among different ethnic groups.

PMID- 30196645
TI  - [Prevalence of anemia during pregnancy in China, 2012-2016: a Meta-analysis].
AB  - Objective: To understand the prevalence and epidemiological features of anemia
      during pregnancy in China. Methods: The literature retrieval was conducted by
      using China Biology Medicine disc (CBMdisc), China National Knowledge
      Infrastructure (CNKI), Wanfang Data, China Science and Technology Journal
      Database (CSTJ), PubMed, Cochrane Library and Embase database. The time was from
      January 2012 to October 2017, and the language was limited to Chinese and
      English. The Chinese and corresponding English search terms included pregnancy,
      anemia, epidemiology and prevalence. Results: A total of 28 papers were included.
      The total number of participants investigated was 58 752, with 11 588 cases with
      anemia during pregnancy identified. The overall prevalence of anemia during
      pregnancy was 19.9% (95%CI: 16.3%-23.5%). The prevalence varied in anemia with
      different levels. The prevalence of mild, moderate and severe anemia were 15.9%
      (95%CI: 11.7%-20.2%), 5.7% (95%CI: 4.5%-6.8%) and 1.3% (95%CI: 0.8%-1.8%)
      respectively. The prevalence of mild anemia was highest and the prevalence of
      severe anemia was lowest. The prevalence of anemia increased with gestational
      weeks. The prevalence of anemia at the first, second and third trimester of
      pregnancy were 10.1% (95%CI: 6.2%-14.0%), 26.7% (95%CI: 18.0%-35.5%) and 28.1%
      (95%CI: 21.0%-35.1%) respectively. Both degree and gestational week subgroup
      analysis showed a significant difference among groups (P<0.05). There were no
      statistically significant differences among subgroups of cut-off year, region,
      resident area, age, education level and parity (P>0.05). Conclusion: The
      prevalence of anemia during pregnancy in China had remained at a low level during
      the past 5 years. The prevalence of mild anemia was higher than that of moderate
      and severe anemia. The prevalence of anemia in women at the second and third
      trimester of pregnancy was higher than that at the first trimester of pregnancy.
      Women at the second and third trimester of pregnancy should be attached a great
      importance in the prevention and control of anemia during pregnancy.

PMID- 30196646
TI  - [Development of rating scale on job competency for preventive medicine graduate].

PMID- 30196647
TI  - [Progress on the research of social contact pattern and infectious diseases
      transmission].
AB  - The pattern of social contact that the connection exists between people in social
      life tends to have certain rules. Hence, studying the laws of social contact of
      the population can improve the accuracy of modeling infectious diseases and
      provide scientific evidences for the spreading and intervention of infectious
      diseases transmitted by droplets or contact. This paper is a review that
      summarizes the current research methods of social contact pattern, the law of
      social contact and its significance to the spreading and prevention of infectious
      diseases. It finds that the survey methods of social contact mainly include
      direct observation, contact diaries and proximity sensors and the social contact
      patterns show regularities in multiple dimensions such as contact time, contact
      location and contact objects. Moreover, these regularities relevant to social
      contact patterns can apply to the mathematical model of infectious diseases and
      the evaluation of the effect of interventions, which provide the effective basis
      for the prevention and control of infectious diseases.

PMID- 30196648
TI  - Development of a multi-channel NIRS-USG hybrid imaging system for detecting
      prostate cancer and improving the accuracy of imaging-based diagnosis: a phantom
      study.
AB  - Purpose: This study aimed to develop a multi-channel near-infrared spectroscopy
      (NIRS) and ultrasonography (USG) fusion imaging system for imaging prostate
      cancer and to verify its diagnostic capability by applying the hybrid imaging
      system to a prostate cancer phantom. Methods: A multi-channel NIRS system using
      the near-infrared 785-nm wavelength with 12 channels and four detectors was
      developed. After arranging the optical fibers around a USG transducer, we
      performed NIRS imaging and grayscale USG imaging simultaneously. Fusion imaging
      was obtained by processing incoming signals and the spatial reconstruction of
      NIRS, which corresponded with grayscale USG acquired at the same time. The NIRS
      USG hybrid system was applied to a silicone-based optical phantom of the prostate
      gland containing prostate cancer to verify its diagnostic capability
      qualitatively. Results: The NIRS-USG hybrid imaging system for prostate cancer
      imaging simultaneously provided anatomical and optical information with 2
      dimensional registration. The hybrid imaging system showed more NIR attenuation
      over the prostate cancer model than over the model of normal prostate tissue. Its
      diagnostic capability to discriminate a focal area mimicking the optical
      properties of prostate cancer from the surrounding background mimicking the
      optical properties of normal prostate tissue was verified by applying the hybrid
      system to a silicone-based optical phantom of prostate cancer. Conclusion: This
      study successfully demonstrated that the NIRS-USG hybrid system may serve as a
      new imaging method for improving the diagnostic accuracy of prostate cancer, with
      potential utility for future clinical applications.

PMID- 30196650
TI  - Prognostic implications of trunk muscle mass in liver cirrhosis.

PMID- 30196649
TI  - Association between Serum Uric Acid and Oxidative Stress in Korean Adults.
AB  - BACKGROUND: Oxidative stress is implicated in the pathogenesis and development of
      lifestyle-related diseases. In the present study, we evaluated the correlation
      between the serum uric acid (UA) levels and oxidative status in Korean adults.
      METHODS: The subjects were 5,093 individuals (2,041 women and 3,052 men) who
      underwent a health checkup between June 2012 and December 2016. Oxidative stress
      levels (derivatives of reactive oxygen metabolites [d-ROMs]) and antioxidant
      potential (biological antioxidant potential [BAP]) were measured. Metabolic
      markers, including UA, were also examined. RESULTS: Higher serum UA levels were
      associated with decreased levels of d-ROMs (P<0.05). The UA levels were
      positively associated with BAP levels (P<0.001). CONCLUSION: Serum UA is related
      to oxidative status, especially antioxidant capacity, in Korean adults; UA may
      play a role in antioxidant defense systems in humans.

PMID- 30196651
TI  - Combination of synbiotic and sitagliptin in nonalcoholic fatty liver disease: Is
      it better than sitagliptin alone?

PMID- 30196652
TI  - Review of the UBC Porcine Model of Traumatic Spinal Cord Injury.
AB  - Traumatic spinal cord injury (SCI) research has recently focused on the use of
      rat and mouse models for in vivo SCI experiments. Such small rodent SCI models
      are invaluable for the field, and much has been discovered about the biologic and
      physiologic aspects of SCI from these models. It has been difficult, however, to
      reproduce the efficacy of treatments found to produce neurologic benefits in
      rodent SCI models when these treatments are tested in human clinical trials. A
      large animal model may have advantages for translational research where
      anatomical, physiological, or genetic similarities to humans may be more relevant
      for pre-clinically evaluating novel therapies. Here, we review the work carried
      out at the University of British Columbia (UBC) on a large animal model of SCI
      that utilizes Yucatan miniature pigs. The UBC porcine model of SCI may be a
      useful intermediary in the pre-clinical testing of novel pharmacological
      treatments, cell-based therapies, and the "bedside back to bench" translation of
      human clinical observations, which require preclinical testing in an applicable
      animal model.

PMID- 30196653
TI  - Can Right-Handed Surgeons Insert Upper Thoracic Pedicle Screws in much
      Comfortable Position? Right-Handedness Problem on the Left Side.
AB  - OBJECTIVE: Thoracic pedicles have special and specific properties. In particular,
      upper thoracic pedicles are positioned in craniocaudal plane. Therefore,
      manipulation of thoracic pedicle screws on the left side is difficult for right
      handed surgeons. We recommend a new position to insert thoracic pedicle screw
      that will be much comfortable for spine surgeons. METHODS: We retrospectively
      reviewed 33 patients who underwent upper thoracic pedicle screw instrumentation.
      In 15 patients, a total of 110 thoracic pedicle screws were inserted to the upper
      thoracic spine (T1-6) with classical position (anesthesiologist and monitor were
      placed near to patient's head. Surgeons were standing classically near to
      patient's body while patients were lying in prone position). In 18 patients, a
      total of 88 thoracic pedicle screws were inserted to the upper thoracic spine
      with the new standing position-surgeons stand by the head of the patient and the
      anesthesia monitor laterally and under patient's belt level. All the operations
      performed by the same senior spine surgeons with the help of C-arm. Postoperative
      computed tomography scans were obtained to assess the screw placement. The screw
      malposition and pedicle wall violations were divided and evaluated separately.
      Cortical penetration were measured and graded at either : 1-2 mm penetration, 2-4
      mm penetration and >4 mm penetration. RESULTS: Total 198 screws were inserted
      with two different standing positions. Of 198 screws 110 were in the classical
      positioning group and 88 were in the new positioning group. Incorrect screw
      placement was found in 33 screws (16.6%). The difference between total screw
      malposition by both standing positions were found to be statistically significant
      (p=0.011). The difference between total pedicle wall violations by both standing
      positions were found to be statistically significant (p=0.003). CONCLUSION: Right
      handedness is a problem during the upper thoracic pedicle screw placement on the
      left side. Changing the surgeon's position standing near to patient's head could
      provide a much comfortable position to orient the craniocaudal plane of the
      thoracic pedicles.

PMID- 30196654
TI  - Can the Zero-Profile Implant Be Used for Anterior Cervical Discectomy and Fusion
      in Traumatic Subaxial Disc Injury? A Preliminary, Retrospective Study.
AB  - OBJECTIVE: The zero-profile implant (Zero-P) is accepted for use in anterior
      cervical fusion for the treatment of degenerative cervical disease. However,
      evidence pertaining to its efficiency and safety in traumatic cervical injury is
      largely insufficient. This study aimed to compare the overall outcomes of
      patients who underwent Zero-P for traumatic cervical disc injury. METHODS: Data
      from a total of 53 consecutive patients who underwent surgery for traumatic or
      degenerative cervical disc disease using the Zero-P were reviewed. Seventeen
      patients (group A) had traumatic cervical disc injury and the remaining 36 (group
      B) had degenerative cervical disc herniation. The fusion and subsidence rates and
      Cobb angle were measured retrospectively from plain radiographs. The patients'
      clinical outcomes were evaluated using the Japanese Orthopedic Association (JOA)
      score and Odom's criteria. RESULTS: The C2-7 Cobb and operative segmental angles
      increased by 3.45+/-7.61 and 2.94+/-4.59 in group A; and 2.46+/-7.31 and 2.88+/
      5.49 in group B over 12 postoperative months, respectively. The subsidence and
      fusion rate was 35.0% and 95.0% in group A; and 36.6% and 95.1% in group B,
      respectively. None of the parameters differed significantly between groups. The
      clinical outcomes were similar in both groups in terms of increasing the JOA
      score and producing a grade higher than "good" using Odom's criteria. CONCLUSION:
      The application of Zero-P in patients with traumatic cervical disc injury was
      found to be acceptable when compared with the clinical and radiological outcomes
      of degenerative cervical spondylosis.

PMID- 30196655
TI  - Predictive Values of Magnetic Resonance Imaging Features for Tracheostomy in
      Traumatic Cervical Spinal Cord Injury.
AB  - OBJECTIVE: To evaluate the magnetic resonance (MR) imaging features that have a
      statistically significant association with the need for a tracheostomy in
      patients with cervical spinal cord injury (SCI) during the acute stage of injury.
      METHODS: This study retrospectively reviewed the clinical data of 130 patients
      with cervical SCI. We analyzed the factors believed to increase the risk of
      requiring a tracheostomy, including the severity of SCI, the level of injury as
      determined by radiological assessment, three quantitative MR imaging parameters,
      and eleven qualitative MR imaging parameters. RESULTS: Significant differences
      between the non-tracheostomy and tracheostomy groups were determined by the
      following five factors on multivariate analysis : complete SCI (p=0.007), the
      radiological level of C5 and above (p=0.038), maximum canal compromise (MCC)
      (p=0.010), lesion length (p=0.022), and osteophyte formation (p=0.015). For the
      MCC, the cut-off value was 46%, and the risk of requiring a tracheostomy was
      three times higher at an interval between 50-60% and ten times higher between 60
      70%. For lesion length, the cut-off value was 20 mm, and the risk of requiring a
      tracheostomy was two times higher at an interval between 20-30 mm and fourteen
      times higher between 40-50 mm. CONCLUSION: The American Spinal Injury Association
      grade A, a radiological injury level of C5 and above, an MCC >=50%, a lesion
      length >=20 mm, and osteophyte formation at the level of injury were considered
      to be predictive values for requiring tracheostomy intervention in patients with
      cervical SCI.

PMID- 30196657
TI  - An Evaluation of the Quality of Sleep Before and After Surgical Treatment of
      Patients with Cervical Disc Herniation.
AB  - OBJECTIVE: It has been reported in recent studies that 50-80% of patients with
      cervical disc hernia have concomitant sleep disorders. The aim of this study was
      to evaluate the quality of sleep before and after surgical treatment in patients
      with cervical disc hernia and to assess the effects on treatment. METHODS: The
      study included 32 patients performed discectomy and fusion with an intervertebral
      cage through the right anterior cervical approach. Oswestry Disability Index
      (ODI), Visual Analog Scale (VAS) and Pittsburgh Sleep Quality Index (PSQI) were
      applied to all patients preoperatively and at one month postoperatively. RESULTS:
      The postoperative PSQI total points and all the PSQI subscale points, the ODI and
      VAS scores were significantly reduced compared to the preoperative values. A
      positive correlation was determined between the preoperative ODI points and the
      PSQI total points and sleep duration, sleep latency and daytime functional loss
      subscale points. A positive correlation was also found between preoperative ODI
      points and VAS points. A positive correlation was determined between the
      preoperative VAS points and and the PSQI total points and sleep duration, and
      sleep latency subscale points. A negative correlation was determined between the
      postoperative ODI and the daytime functional loss subscale points. CONCLUSION:
      The results of the study showed that in patients with cervical disc hernia, sleep
      quality and daytime functionality were negatively affected by severity of pain
      that limited daily activities. Bringing the pain under control with surgical
      treatment was observed to increase sleep quality. It can be concluded that when
      planning treatment for these patients, it should be taken into consideration that
      there could be a sleep disorder in addition to the complaints and symptoms such
      as pain, hypoestesia and loss of strength.

PMID- 30196658
TI  - Prospective Multicenter Surveillance Study of Surgical Site Infection after
      Spinal Surgery in Korea : A Preliminary Study.
AB  - OBJECTIVE: This study aimed to investigate the rates, types, and risk factors of
      surgical site infection (SSI) following spinal surgery using data from a Korean
      SSI surveillance system that included diagnoses made by surgeons. METHODS: This
      was a prospective observational study of patients who underwent spinal surgeries
      at 42 hospitals in South Korea from January 2017 to December 2017. The procedures
      included spinal fusion, laminectomy, discectomy, and corpectomy. Univariate and
      multivariate logistic regression analyses were performed. RESULTS: Of the 3080
      cases included, 30 showed infection, and the overall SSI rate was 1.0% (an
      incidence of 1.2% in spinal fusion and 0.6% in laminectomy). Deep incisional
      infections were the most common type of SSIs (46.7%). Gram-positive bacteria
      caused 80% of the infections, and coagulase-negative staphylococci, including
      Staphylococcus epidermidis, accounted for 58% of the grampositive bacteria. A
      longer preoperative hospital stay was significantly associated with the incidence
      of SSI after both spinal fusion and laminectomy (p=0.013, p<0.001). A combined
      operation also was associated with SSI after laminectomy (p=0.032). CONCLUSION:
      An SSI surveillance system is important for the accurate analysis of SSI. The
      incidence of SSI after spinal surgery assessed by a national surveillance system
      was 1.0%. Additional data collection will be needed in future studies to analyze
      SSI in spinal surgery.

PMID- 30196656
TI  - Gamma Knife Radiosurgery for Metastatic Brain Tumors with Exophytic Hemorrhage.
AB  - OBJECTIVE: Metastatic brain tumors (MBTs) often present with intracerebral
      hemorrhage. Although Gamma Knife surgery (GKS) is a valid treatment option for
      hemorrhagic MBTs, its efficacy is unclear. To achieve oncologic control and
      reduce radiation toxicity, we used a radiosurgical targeting technique that
      confines the tumor core within the hematoma when performing GKS in patients with
      such tumors. We reviewed our experience in this endeavor, focusing on local tumor
      control and treatment-associated morbidities. METHODS: From 2007 to 2014, 13
      patients with hemorrhagic MBTs were treated via GKS using our targeting
      technique. The median marginal dose prescribed was 23 Gy (range, 20-25). GKS was
      performed approximately 2 weeks after tumor bleeding to allow the patient's
      condition to stabilize. RESULTS: The primary sites of the MBTs included the liver
      (n=7), lung (n=2), kidney (n=1), and stomach (n=1); in two cases, the primary
      tumor was a melanoma. The mean tumor volume was 4.00 cm3 (range, 0.74-11.0). The
      mean overall survival duration after GKS was 12.5 months (range, 3-29), and three
      patients are still alive at the time of the review. The local tumor control rate
      was 92% (tumor disappearance 23%, tumor regression 46%, and stable disease 23%).
      There was one (8%) instance of local recurrence, which occurred 11 months after
      GKS in the solid portion of the tumor. No GKS-related complications were
      observed. CONCLUSION: Our experience shows that GKS performed in conjunction with
      our targeting technique safely and effectively treats hemorrhagic MBTs. The
      success of this technique may reflect the presence of scattered metastatic tumor
      cells in the hematoma that do not proliferate owing to the inadequate
      microenvironment of the hematoma. We suggest that GKS can be a useful treatment
      option for patients with hemorrhagic MBTs that are not amenable to surgery.

PMID- 30196659
TI  - Cubital Tunnel Syndrome Caused by Anconeus Epitrochlearis Muscle.
AB  - OBJECTIVE: We evaluated the clinical manifestation and surgical results following
      operative treatment of cubital tunnel syndrome (CuTS) caused by anconeus
      epitrochlearis (AE) muscle. METHODS: Among 142 patients who underwent surgery for
      CuTS from November 2007 to October 2015, 12 were assigned to the AE group based
      on discovery of AE muscle; 130 patients were assigned to the other group. We
      analyzed retrospectively; age, sex, dominant hand, symptom duration, and weakness
      in hand. Severity of the disease was evaluated using the Dellon classification
      and postoperative symptom were evaluated using disability of arm shoulder and
      hand (DASH) and visual analogue scale (VAS) scores. Surgery consisted of
      subfascial anterior transposition following excision of AE muscle. RESULTS: AE
      muscle was present in 8.5% of all patients, and was more common in patients who
      were younger and with involvement of their dominant hand; the duration of symptom
      was shorter in patients with AE muscle. All patients showed postoperative
      improvement in symptoms according to DASH and VAS scores. CONCLUSION: The
      possibility of CuTS caused by AE muscle should be considered when younger
      patients have rapidly aggravated and activity-related cubital tunnel symptoms
      with a palpable mass in the cubital tunnel area. Excision of AE muscle and
      anterior ulnar nerve transposition may be considered effective surgical
      treatment.

PMID- 30196660
TI  - Analysis According to Characteristics of 18 Cases of Brachial Plexus Tumors : A
      Review of Surgical Treatment Experience.
AB  - OBJECTIVE: Because the anatomical structure of the brachial plexus is very
      complex, surgical treatment of tumors in this region is challenging. Therefore, a
      lot of clinical and surgical experience is required for successful treatment;
      however, many neurosurgeons have difficulty accumulating this experience owing to
      the rarity of brachial plexus tumors. The purpose of this report is to share our
      surgical experience with brachial plexus tumor with other neurosurgeons. METHODS:
      The records of 18 consecutive patients with brachial plexus tumors who underwent
      surgical treatment between January 2010 and December 2017 in a single institution
      were retrospectively reviewed. The surgical approach was determined according to
      the tumor location and size, and intraoperative neurophysiological monitoring
      (IONM) was used in most of cases to prevent iatrogenic nerve injury during
      surgery. In addition, to evaluate the differences in tumor characteristics
      according to pathologic diagnosis, the tumors were divided twice into two groups,
      based on two separate classifications, and statistical analysis was performed.
      RESULTS: The 18 brachial plexus tumors comprised 15 (83.3%) benign peripheral
      nerve sheath tumors including schwannoma and neurofibroma, one (5.6%) malignant
      peripheral nerve sheath tumor, one (5.6%) benign tumor of non-neural sheath
      origin (neurogenic cyst), and one (5.6%) metastatic tumor (papillary carcinoma).
      The authors analyzed relationship between tumor size/ location and tumor
      characteristic parameters such as age, size, right-left, and pathology. There
      were no statistically significant differences except a tendency of bigger tumor
      size in young age. CONCLUSION: For a successful surgical outcome, an appropriate
      surgical approach is essential, and the appropriate surgical approach is
      determined by the location and size of the tumor. Furthermore, applying IONM may
      prevent postoperative complications and it is favorable option for brachial
      plexus tumors surgery.

PMID- 30196661
TI  - A Novel Implantable Cerebrospinal Fluid Reservoir : A Pilot Study.
AB  - OBJECTIVE: The purpose of this pilot study was to examine the safety and function
      of the newly developed cerebrospinal fluid (CSF) reservoir called the V-Port.
      METHODS: The newly developed V-Port consists of a non-collapsible reservoir
      outlined with a titanium cage and a connector for the ventricular catheter to be
      assembled. It is designed to be better palpated and more durable to multiple
      punctures than the Ommaya reservoir. A total of nine patients diagnosed with
      leptomeningeal carcinomatosis were selected for V-Port insertion. Each patient
      was followed up for evaluation for a month after the operation. RESULTS: The
      average operation time for V-Port insertion was 42 minutes and the average
      incision size was 6.6 cm. The surgical technique of V-Port insertion was found to
      be intuitive by all neurosurgeons who participated in the pilot study. There was
      no obstruction or leakage of the V-Port during intrathecal chemotherapy or CSF
      drainage. Also, there were no complications including post-operative
      intracerebral hemorrhage, infection and skin problems related to the V-Port.
      CONCLUSION: V-Port is a safe and an easy to use implantable CSF reservoir that
      addresses problems of other implantable CSF reservoirs. Further multicenter
      clinical trial is needed to prove the safety and the function of the V-Port.

PMID- 30196662
TI  - Prospective Multicenter Surveillance Study of Surgical Site Infection after
      Intracranial Procedures in Korea : A Preliminary Study.
AB  - OBJECTIVE: This study aimed to investigate the rates, types, and risk factors of
      surgical site infection (SSI) following intracranial neurosurgical procedures
      evaluated by a Korean SSI surveillance system. METHODS: This was a prospective
      observational study of patients who underwent neurosurgical procedures at 29
      hospitals in South Korea from January 2017 to June 2017. The procedures included
      craniectomy, craniotomy, cranioplasty, burr hole, and ventriculoperitoneal shunt.
      Univariate and multivariate logistic regression analyses were performed. RESULTS:
      Of the 1576 cases included, 30 showed infection, for an overall SSI rate of 1.9%.
      Organ/space infection was the most common, found in 21 out of the 30 cases (70%).
      Staphylococcus aureus was the most common (41%) of all bacteria, and Serratia
      marcescens (12%) was the most common among gram-negative bacteria. In univariate
      analyses, the p-values for age, preoperative hospital stay duration, and over T
      hour were <0.2. In a multivariate analysis of these variables, only preoperative
      hospital stay was significantly associated with the incidence of SSI (p<0.001),
      whereas age and over T-hour showed a tendency to increase the risk of SSI (p=0.09
      and 0.06). CONCLUSION: Surveillance systems play important roles in the accurate
      analysis of SSI. The incidence of SSI after neurosurgical procedures assessed by
      a national surveillance system was 1.9%. Future studies will provide clinically
      useful results for SSI when data are accumulated.

PMID- 30196663
TI  - Research Progress on Leptotrombidium deliense.
AB  - This article reviews Leptotrombidium deliense, including its discovery and
      nomenclature, morphological features and identification, life cycle, ecology,
      relationship with diseases, chromosomes and artificial cultivation. The first
      record of L. deliense was early in 1922 by Walch. Under the genus
      Leptotrombidium, there are many sibling species similar to L. deliense, which
      makes it difficult to differentiate L. deliense from another sibling chigger
      mites, for example, L. rubellum. The life cycle of the mite (L. deliense)
      includes 7 stages: egg, deutovum (or prelarva), larva, nymphochrysalis, nymph,
      imagochrysalis and adult. The mite has a wide geographical distribution with low
      host specificity, and it often appears in different regions and habitats and on
      many species of hosts. As a vector species of chigger mite, L. deliense is of
      great importance in transmitting scrub typhus (tsutsugamushi disease) in many
      parts of the world, especially in tropical regions of Southeast Asia. The
      seasonal fluctuation of the mite population varies in different geographical
      regions. The mite has been successfully cultured in the laboratory, facilitating
      research on its chromosomes, biochemistry and molecular biology.

PMID- 30196665
TI  - Survey on Intestinal Helminthic Infection Status of Students in Two Counties,
      Hadong-gun and Goseong-gun, Korea.
AB  - This study was conducted to investigate the prevalence of intestinal parasites
      among students from Goseonggun, Gangwon-do and Hadong-gun, Gyeongsangnam-do as
      typical low and high endemic counties. From May to July 2017, a total of 2,033
      fecal samples were collected at 27 elementary, 10 junior high, and 8 high schools
      from 2 counties and examined by the Kato-Katz technique for egg-positive surveys
      (Collection rate: 37.02% [2,033/5,492]). Of the participants examined, 13 (0.64%)
      were found to harbor eggs of 3 parasitic species, Trichuris trichiura, Clonorchis
      sinensis and Metagonimus yokogawai. Based on the regional distribution, the egg
      positive rate in Goseong-gun was 0% (0/550) and that in Hadong-gun was 0.88%
      (13/1,483). The positive rates for C. sinensis, M. yokogawai, and T. trichiura in
      Hadonggun were 0.20% (3/1,483), 0.61% (9/1,483), and 0.07% (1/1,483),
      respectively. The present survey showed that the prevalence of parasitic
      infection among students is currently very low even in remote, previously endemic
      areas, and the present status of parasitic diseases can be summarized as some
      transmission of fish/food-borne trematodes. Thus, it is necessary to carefully,
      continuously monitor the trematode infection status, particularly of C. sinensis
      and M. yokogawai.

PMID- 30196664
TI  - Evaluation of Protective Immune Response Induced by a DNA Vaccine Encoding GRA8
      against Acute Toxoplasmosis in a Murine Model.
AB  - Toxoplasma gondii is an apicomplexan zoonotic protozoan parasite that infects
      most species of warm-blooded animals, including humans. The heavy incidence and
      severe or lethal damage caused by T. gondii infection clearly indicate a need for
      the development of an effective vaccine. T. gondii GRA8 is a member of the dense
      granules protein family and is used as a marker of acute infection. In the
      present study, we evaluated the protective immunity induced by DNA vaccination
      based on a recombinant eukaryotic plasmid, pDsRed2-GRA8, against acute
      toxoplasmosis in mice. BALB/c mice were intramuscularly immunized with the
      pDsRed2-GRA8 plasmid and then challenged by infection with the highly virulent
      GFP-RH strain of T. gondii. The specific immune responses and protective efficacy
      against T. gondii of this vaccine were analyzed by measuring cytokine and serum
      antibody titers, splenocyte proliferation assays, and the survival times of mice
      after challenge. Our results showed that mice immunized with pDsRed2-GRA8
      demonstrated specific humoral and cellular responses, induced higher IgG antibody
      titers with predominant IgG2a production; increased levels of IL-10, IL-12 (p70),
      IFN-gamma, TNF-alpha, and splenocyte proliferation; and prolonged survival times
      compared to those of control mice. The present study showed that DNA immunization
      with pDsRed2-GRA8 induced humoral and cellular immune responses, and all
      immunized mice showed greater Th1-type immune responses and longer survival times
      than those of control mice. These results indicated that T. gondii GRA8 DNA
      immunization induces a partial protective effect against acute toxoplasmosis.

PMID- 30196666
TI  - Infections with Centrocestus armatus Metacercariae in Fishes from Water Systems
      of Major Rivers in Republic of Korea.
AB  - The infection status of Centrocestus armatus metacercariae (CaMc) was broadly
      surveyed in freshwater fishes from major river systems in the Republic of Korea
      (Korea) during 2008-2017. A total of 14,977 fishes was caught and examined by the
      artificial digestion method. CaMc were detected in 3,818 (97.1%) (2,114 Z.
      platypus: 96.1% and 1,704 Z. temminckii: 98.4%) out of 3,932 Zacco spp. examined
      and their density was 1,867 (2,109 in Z. platypus and 1,567 in Z. temminckii) per
      fish infected. The prevalences with CaMc were high, 93.7-100%, in Zacco spp. from
      all surveyed areas. However, their densities were more or less different by the
      surveyed areas and fish species. They were most high in Nakdong-gang in
      Gyeongsangnam-do (4,201 in average), and followed by Geum-gang (2,343), Nakdong
      gang in Gyeongsangbuk-do (1,623), Han-gang (1,564), Tamjin-gang and Yeongsan-gang
      (1,540), streams in the east coast (1,028), Seomjin-gang (488) and Mangyeong-gang
      (170). In another species of rasborinid fish, Opsariichthys uncirostris
      amurensis, CaMc were detected in 222 (74.8%) out of 297 ones examined and their
      density was 278 (1-4,480) per fish infected. CaMc were also detected in total 41
      fish species except for the rasborinid fish, Z. platypus, Z. temminckii and O.
      uncirostris amurensis. Conclusively, it was confirmed that among the 3 species of
      rasborinid fish, Z. platypus and Z. temminckii are highly prevalent and O.
      uncirostris amurensis is moderately prevalent with CaMc. Additionally, we could
      know that variety of fish species act as the second intermediate hosts of C.
      armatus in Korea.

PMID- 30196667
TI  - Infection Status with Metagonimus spp. Metacercariae in Fishes from Seomjin-gang
      and Tamjin-gang in Republic of Korea.
AB  - To grasp the infection status of Metagonimus spp. metacercariae (MsMc), the
      freshwater fishes were surveyed from Seomjin-gang (river) and Tamjin-gang in the
      Republic of Korea. Total 1,604 fishes from 7 local sites of Seomjin-gang and
      1,649 fishes from 2 sites of Tamjin-gang were examined for 6 years (2012-2017) by
      the artificial digestion method. MsMc were detected in fishes from 7 sites, i.e.,
      Osucheon in Imsil-gun (36.3% fish in 6 spp.), Seomjin-gang in Sunchanggun (49.8%
      in 18 spp.), Songdaecheon in Namwon-si (64.5% in 8 spp.), Seomjin-gang in
      Gokseong-gun (72.4% in 14 spp.) and in Gurye-gun (78.8% in 17 spp.), Hoengcheon
      (75.9% in 11 spp.) and Namsancheon (58.9% in 7 spp.) in Hadong-gun. Their average
      densities were 4.2, 86.8, 39.9, 43.1, 246.5, 173.6 and 67.5 per fish infected
      respectively. Prevalence with MsMc in rasborinid fish from Seomjin-gang was 89.2%
      and their intensity was 73.6 per fish infected. Endemicities of MsMc in
      rasborinid fish from Seomjin-gang were significantly higher in fishes from the
      lower reaches (prevalence: 98.7%; density: 137) rather than in fishes from the
      middle (93.5%; 38) and upper (72.4%; 13) reaches. MsMc were also detected in
      56.1% and 66.4% fishes from 2 surveyed areas, i.e., the middle reaches in
      Jangheung-gun and the lower reaches in Gangjin-gun, of Tamjin-gang, and their
      densities were 147 and 121 per fish infected. In susceptible fishes from Tamjin
      gang, the prevalence was 84.1% and density was 227 per fish infected. By the
      present study, it was confirmed that MsMc is highly prevalent in the fishes from
      Seomjin-gang and Tamjin-gang in Korea.

PMID- 30196668
TI  - Molecular Genetic Findings of Spirometra decipiens and S. ranarum in Korea.
AB  - The taxonomy of Spirometra species has been controversial despite the medical and
      veterinary importance. Currently, only a few Spirometra species are considered
      valid species in the genus Spirometra. In the present study, the distribution of
      Spirometra species obtained from animals in Korea were identified by molecular
      analysis of the mitochondrial cytochrome c oxidase I (cox1) gene. A total of 28
      Spirometra species specimens were analyzed. These were all collected between 1973
      and 2008 in the Republic of Korea. Mitochondrial cox1 sequences were examined for
      a total of 28 specimens comprising 14 S. decipiens and 14 S. ranarum. The
      difference in partial cox1 sequences (316 bp) between S. erinaceieuropaei
      (KJ599680) and S. ranarum (this study) was 9.3%, while that between S. decipiens
      (KJ599679) and S. ranarum (this study) was 2.2%. Genetic analyses identified 2
      Spirometra species in animals such as cat, leopard cat, dog, duck and snake in
      Korea as S. decipiens and S. ranarum. S. decipiens and S. ranarum were present in
      Gyeongnam Province (P), Jeonnam P, Gangwon P, Chungbuk P, and Seoul. S. decipiens
      was found in tadpoles, snakes, ducks, cats, leopard cats and dogs, while S.
      ranarum was found in cats and dogs. The ratio of S. decipiens:S. ranarum
      calculated from the molecular data was 14:14 (or 1:1). These results indicate
      that S. decipiens and S. ranarum are sympatrically distributed in Korea.

PMID- 30196669
TI  - Molecular Identification of Bartonella melophagi and Wolbachia Supergroup F from
      Sheep Keds in Xinjiang, China.
AB  - To confirm that Bartonella and Wolbachia were carried by sheep keds (Melophagus
      ovinus) in southern Xinjiang of China, 17 M. ovinus samples, which were collected
      in Aksu Prefecture, Xinjiang, were randomly selected. In this study, the
      Bartonella gltA and Wolbachia 16S rRNA gene were amplified through conventional
      PCR and the sequence of those amplified products, were analyzed. The results
      demonstrated that Bartonella was carried by all of the 17 sheep keds and
      Wolbachia was carried by 15 out of them. Bartonella was identified as B.
      melophagi. Three strains of Wolbachia were supergroup F and 1 strain has not been
      confirmed yet. It is the first report about Wolbachia supergroup F was found in
      sheep keds and provided the molecular evidence that B. melophagi and Wolbachia
      supergroup F were carried by sheep keds in Aksu Prefecture of southern Xinjiang,
      China. The 2 pathogens were found in sheep keds around Taklimakan Desert for the
      first time.

PMID- 30196670
TI  - Identification of Cystoisospora ohioensis in a Diarrheal Dog in Korea.
AB  - A 3-month-old female Maltese puppy was hospitalized with persistent diarrhea in a
      local veterinary clinic. Blood chemistry and hematology profile were analyzed and
      fecal smear was examined. Diarrheal stools were examined in a diagnostic
      laboratory, using multiplex real-time polymerase chain reaction (PCR) against 23
      diarrheal pathogens. Sequence analysis was performed using nested PCR amplicon of
      18S ribosomal RNA. Coccidian oocysts were identified in the fecal smear. Although
      multiplex real-time PCR was positive for Cyclospora cayetanensis, the final
      diagnosis was Cystoisospora ohioensis infection, confirmed by phylogenetic
      analysis of 18S rRNA. To our knowledge, this the first case report of C.
      ohioensis in Korea, using microscopic examination and phylogenetic analysis.

PMID- 30196671
TI  - A Case of Fascioliasis in A Wild Nutria, Myocastor coypus, in Republic of Korea.
AB  - A total of 44 adult or juvenile nutrias were necropsied for disease survey. A
      large nodule was found in the liver of a nutria. The histopathological specimen
      of the hepatic nodule was microscopically examined, and sectional worms were
      found in the bile duct. The worms showed a tegument with spines, highly branches
      of vitelline glands and intestine. Finally, we histopathologically confirmed
      fascioliasis in a wild nutria. In the present study, a case of fascioliasis in a
      wild nutria is first confirmed in Korea.

PMID- 30196672
TI  - Molecular and Morphologic Identification of Spirometra ranarum Found in the Stool
      of African Lion, Panthera leo in the Serengeti Plain of Tanzania.
AB  - The present study was performed with morphological and molecular analysis (cox1
      and nad1 mitochondrial genes) to identify the proglottids of spirometrid tapeworm
      found in the stool of an African lion, Panthera leo, in the Serengeti plain of
      Tanzania. A strand of tapeworm strobila, about 75 cm in length, was obtained in
      the stool of a male African lion in the Serengeti National Park (34 50' E, 02 30'
      S), Tanzania, in February 2012. The morphological features of the adult worm
      examined exhibited 3 uterine coils with a bow tie appearance and adopted a
      diagonal direction in the second turn. The posterior uterine coils are larger
      than terminal uterine ball and the feature of uteri are swirling rather than
      spirally coiling. The sequence difference between the Spirometra species
      (Tanzania origin) and S. erinaceieuropaei (GenBank no. KJ599680) was 9.4% while
      those of S. decipiens (GenBank no. KJ599679) differed by 2.1% in the cox1 and
      nad1 genes. Phylogenetic tree topologies generated using the 2 analytic methods
      were identical and presented high level of confidence values for the 3 major
      branches of the 3 Spirometra species in the cox1 gene. The morphological and
      molecular findings obtained in this study were nearly coincided with those of S.
      ranarum. Therefore, we can know for the first time that the African lion,
      Panthera leo, is to the definitive host of this tapeworm.

PMID- 30196673
TI  - A Retrospective Analysis on the Cystic Echinococcosis Cases Occured in
      Northeastern Punjab Province, Pakistan.
AB  - A retrospective study was performed to report the case occurrence of cystic
      echinococcosis (CE) in three hospitals of north-eastern region in Punjab
      Province, Pakistan. We reviewed retrospectively the clinical records of patients
      in 4 hospitals which were diagnosed with CE during 2012-2017. A total of 198
      cases, 82 (41.4%) male and 116 (58.6%) females were detected as CE. The most
      Highest incidence was revealed in.... 21-30 years-old group (24.2%) followed by
      41-50 (22.7%), 31-40 (16.2%), 11-20 (13.6%), 51-60 (8.1%), below 10 (5.5%), over
      71 (5.1%) and 61-70 year-old group (4.5%). CE was detected in various organs of
      infected individuals. However, most of CE cases were detected in the liver
      (47.4%) and lung (18.6%). The present study indicated that CE is more or less
      prevalent in surveyed areas and one of the most important public health problems
      in Punjab Province, Pakistan.

PMID- 30196675
TI  - Robot-Assisted Spine Surgery: A Solution for Aging Spine Surgeons.

PMID- 30196676
TI  - The 16th Summer Intensive Course & the EACON 2018.

PMID- 30196674
TI  - Genetic Diversity of Echinococcus granulosus Genotype G1 in Xinjiang, Northwest
      of China.
AB  - Cystic echinococcosis (CE) caused by E. granulosus is a serious helminthic
      zoonosis in humans, livestock and wildlife. Xinjiang is one of high endemic
      province for CE in China. A total of 55 sheep and cattle livers containing
      echinococcal cysts were collected from slaughterhouses in Changji and Yining
      City, northern region of Xinjiang. PCR was employed for cloning 2 gene fragments,
      12S rRNA and CO1 for analysis of phylogenetic diversity of E. granulosus. The
      results showed that all the samples collected were identified as G1 genotype of
      E. granulosus. Interestingly, YL5 and CJ75 strains were the older branches
      compared to those strains from France, Argentina, Australia. CO1 gene fragment
      showed 20 new genotype haploids and 5 new genotype haplogroups (H1-H5) by the
      analysis of Network 5.0 software, and the YLY17 strain was identified as the most
      ancestral haplotype. The major haplotypes, such as CJ75 and YL5 strains, showed
      identical to the isolates from Middle East. The international and domestic trade
      of livestock might contribute to the dispersal of different haplotypes for E.
      granulosus evolution.

PMID- 30196677
TI  - New Pathophysiological Considerations on Cerebral Aneurysms.
AB  - Cerebral aneurysm is a common cerebrovascular disease that is sometimes
      complicated by rupture or an enlarged mass. We are now aggressively evaluating
      and managing unruptured cerebral aneurysms based on a significant concern for the
      high morbidity and mortality related to its associated complications. However,
      the actual rupture rate is very low and the diagnostic and treatment modalities
      are expensive and invasive, which may lead to unnecessary costs and potential
      medical complications. This disproportionate situation is related to a poor
      understanding of the natural course and pathophysiology of cerebral aneurysms. In
      consideration of the concept that not all cerebral aneurysms must be removed, we
      need to examine their course and progression more accurately. Cerebral aneurysms
      may follow a variety of pathophysiological scenarios over their lifetime, from
      formation to growth and rupture. The disease course and the final outcome can
      differ depending on the timing and intensity of the pathological signals acting
      on the cerebral vessel wall. We should delineate a method of predicting the
      stability and risk of rupture of the lesion based on a comprehensive knowledge of
      the vessel wall integrity. This review deals with the basic knowledge and
      advanced concepts underlying the pathophysiology of cerebral aneurysms.

PMID- 30196678
TI  - Endovascular Treatment in Acute Ischemic Stroke: A Nationwide Survey in Korea.
AB  - PURPOSE: As endovascular therapy (EVT) has been approved as a treatment guideline
      for acute ischemic stroke (AIS), it has been increasing in Korea. We conducted a
      nationwide survey to evaluate the current status of EVT for patients with AIS in
      Korea. MATERIALS AND METHODS: An electronic survey was sent to a representative
      clinician at each hospital where EVT was available in Korea. A Google survey was
      used to distribute the questionnaires and receive responses from October 2017 to
      December 2017. RESULTS: Among 120 hospitals in our society, 76 participated in
      this survey. In 26% of the hospitals, more than 50 annual cases of EVT were
      performed, and 25-50 annual cases in 37%. Fifty-six hospitals (73.7%) achieved
      successful recanalization (thrombolysis in cerebral infarction >=2b) in more than
      80% of patients. Computed tomography (CT) angiography was the most common imaging
      modality for AIS treatment, and magnetic resonance (MR) diffusion, MR
      perfusion/diffusion, and perfusion CT were frequently used in order. Non
      eligibility criteria for EVT included a National Institutes of Health Stroke
      Scale <4 (64.5%), the absence of MR perfusion/diffusion mismatch (52.6%), and a
      low Alberta Stroke Program Early CT Score (42.1%). For anterior circulation
      stroke, 60% of Korean hospitals adopted a wider time range of "8 hours" from
      symptom onset, while 70% of hospitals had a time limitation of 12-24 hours for
      posterior circulation stroke. The most preferred EVT device was a stentriever
      (89.4%). In the failed cases due to underlying stenosis, 79% of Korean hospitals
      performed angioplasty or stenting for revascularization. CONCLUSION: This first
      nationwide survey showed that most Korean hospitals conducted EVT for AIS
      patients according to the present guideline in the era of mechanical thrombectomy
      by integrating the clinical experiences of many medical institutions and
      specialists.

PMID- 30196679
TI  - Characteristic Signs on T2*-Based Imaging and Their Relationship with Results of
      Reperfusion Therapy for Acute Ischemic Stroke: A Systematic Review and Evidence
      to Date.
AB  - PURPOSE: Characteristic signs - the susceptibility vessel sign (SVS) and the
      prominent hypointense vessel sign (PHVS) - on T2*-based magnetic resonance
      imaging (T2*MRI) can be seen for acute ischemic stroke with large artery
      occlusion. In this study, we investigated the evidence to support our hypothesis
      that these findings may help to predict outcomes after reperfusion therapy.
      MATERIALS AND METHODS: We searched for papers describing SVS and PHVS in patients
      treated with reperfusion therapy for acute ischemic stroke, and their
      functional/radiologic outcomes were systematically reviewed. RESULTS: Nine
      studies on the SVS and six studies on the PHVS were included. The pooled odds
      ratio (OR) of recanalization after intravenous thrombolysis or mechanical
      thrombectomy was not significantly different with the presence of SVS (OR, 0.615;
      95% confidence interval [CI], 0.335-1.131 and OR, 0.993; 95% CI, 0.629-1.567).
      The OR of favorable functional outcome after reperfusion therapy in terms of the
      presence of PHVS varied (0.083 to 1.831) by study. CONCLUSION: Our meta-analysis
      of the published data showed that a SVS was not a predictive factor for
      recanalization after reperfusion therapy for acute ischemic stroke. Currently,
      the data available on T2*MRI are too limited to warrant reperfusion therapy in
      routine practice. More data are needed from studies with randomized treatment
      allocation to determine the role of T2*MRI.

PMID- 30196680
TI  - Contact Aspiration versus Stent-Retriever Thrombectomy for Distal Middle Cerebral
      Artery Occlusions in Acute Ischemic Stroke: Meta-Analysis.
AB  - PURPOSE: The evidence for endovascular therapy and choice of technique in distal
      middle cerebral artery (MCA) M2 segment occlusions in acute ischemic stroke
      remains controversial. We aimed to conduct a systematic review and meta-analysis
      primarily comparing reperfusion rates of stent-retrieval versus contact
      aspiration for M2 occlusions. MATERIALS AND METHODS: Study selection included
      cohorts of patients with distal MCA occlusions in acute ischemic strokes treated
      with an endovascular approach including stent-retrieval or contact aspiration.
      Twelve studies were selected for meta-analysis for a total of 835 cases. Meta
      analysis by proportions was conducted on parameters including baseline and
      procedural characteristics, thrombolysis in cerebral infarction (TICI) 2b-3
      outcomes, and 90-day modified Rankin scale (mRS) outcomes. RESULTS: Hypertension
      and hyperlipidemia were more prevalent in stent-retriever patients. Pooled
      baseline National Institute of Health Stroke Scale scores and Alberta Stroke
      Program Early Computed Tomography Score imaging scores were similar. Pooled time
      onset of symptoms to door arrival was higher for the stent-retrieval group (154
      vs. 97.4 minutes, P=0.01), as was time to groin puncture (259.9 vs. 156.2
      minutes, P=0.02), but there was no difference in procedure time. The TICI 2b-3
      recanalization rate was similar (80.5% vs. 86.8%, P=0.168). The frequency of mRS
      0-2 at 90-day was also similar (74.5% vs. 59.9%, P=0.120), and an excellent mRS 0
      1 was lower for stent-retrievers (39.9% vs. 65.6%, P=0.003). A significant
      negative correlation was found between onset to groin puncture time and the
      proportion of patients with a good mRS (r=-0.71, P=0.048). CONCLUSION: Both
      endovascular techniques achieved recanalization rates greater than 80% and 90-day
      outcomes of minimal disability with similar complication rates. The literature is
      skewed by aspiration cases being performed sooner after onset of stroke compared
      to stent-retriever cases.

PMID- 30196681
TI  - Patient Radiation Dose in Neurointerventional Radiologic Procedure: A Tertiary
      Care Experience.
AB  - PURPOSE: Neurointerventional radiology procedures often require a long time to
      perform. Patient radiation dose is an important issue due to the hazards of
      ionizing radiation. The objective of this study was to measure the peak skin dose
      (PSD) and effective dose to estimate the deterministic and stochastic effects of
      a therapeutic interventional neuroradiologic procedure. MATERIALS AND METHODS:
      The cumulative dose (CD) and dose area product (DAP) were automatically recorded
      by a fluoroscopic machine and collected prospectively between April and November
      2015. The study included 54 patients who underwent therapeutic
      neurointerventional radiology procedures. The CD of each patient was used to
      estimate the peak skin dose and the DAP was also calculated to estimate the
      effective dose. RESULTS: The average estimated peak skin dose was 1,009.68 mGy.
      Two patients received radiation doses of more than 2 Gy, which is the threshold
      that may cause skin complications and radiation-induced cataract. The average
      effective dose was 35.32 mSv. The majority of patients in this study (85.2%) who
      underwent therapeutic neurointerventional radiologic procedures received
      effective doses greater than 20 mSv. CONCLUSION: Not all therapeutic
      neurointerventional radiology procedures are safe from deterministic
      complications. A small number of patients received doses above the threshold for
      skin complications and radiation induced cataract. In terms of stochastic
      complications, most neurointerventional radiology procedures in this study were
      quite safe in terms of radiation-induced cancer.

PMID- 30196682
TI  - In Vitro Evaluation of Fusiform-Shaped Stents for Wide-Neck Intracranial Aneurysm
      Treatment.
AB  - PURPOSE: Wide-neck aneurysms (WNAs) associated with a dilated parent artery (PA)
      are not uncommon morphological abnormalities and usually cause inappropriate wall
      apposition and incomplete neck coverage of a tubular stent in stent-assisted
      coiling of aneurysms. We aimed to introduce a fusiform-shaped stent (FSS) and
      test its effectiveness in treating intracranial WNAs associated with a dilated PA
      using a three-dimensional (3D) model. MATERIALS AND METHODS: Two FSS types were
      designed with the middle one-third segment dilated by 10% (FSS10) and 20% (FSS20)
      and were compared with the tubular-shaped stent (TSS). A patient-specific 3D WNA
      model was prototyped and produced, and in vitro stent placement was performed.
      Angiographic images of the three stent types were analyzed and compared using
      predetermined parameters. RESULTS: The stent lumens were significantly larger in
      FSS10 and FSS20 than in TSS in the middle segments (P=0.046), particularly FSS20
      (P=0.018). The non-covered area at the ostium tended to be smaller in FSS10 and
      FSS20 than in TSS, but the difference was not significant (P>0.05). The stent
      length was significantly longer in FSS10 and FSS20 than in TSS. The stent cell
      size was significantly larger in FSS than in TSS. CONCLUSION: Better vessel wall
      apposition and aneurysmal neck coverage was observed for FSS than for TSS. No
      significant difference was observed between FSS10 and FSS20.

PMID- 30196683
TI  - Low-Dose Prasugrel in Patients with Resistance to Clopidogrel for the Treatment
      of Cerebral Aneurysms.
AB  - Thromboembolism is one of the major complications of stent assisted coiling in
      treatment of cerebral aneurysm. Clopidogrel resistance is so common and prasugrel
      is more effective in its rapid and potent effect. We investigated changes in the
      value of P2Y12 resistance unit (PRU) when prasugrel was administered to patients
      with clopidogrel resistance. One hundred mg of aspirin and 75 mg of clopidogrel
      were administered for 5 days before the procedure, and PRU were examined. The
      resistance to clopidogrel was defined as the inhibition of PRU was less than 20%.
      PRU was re-examined after loading 20 mg of prasugrel. We treated 98 consecutive
      patients between January 2018 and July 2018, and 24 patients (24.5%) had
      resistance to clopidogrel. Nineteen patients were female. The mean PRU value at
      admission was 238.5+/-36.9 and the percentage inhibition value was 4.8+/-6.3%.
      After the use of prasugrel, the mean PRU and percentage inhibition values were
      measured as 124.9+/-49.9 and 48.0+/-19.24, respectively. All patients except one
      patient had a PRU inhibition value as a responder. There was no hemorrhage or
      thromboembolic complication during mean 1.5 months follow-up after embolization
      procedure. In conclusion, in patients resistant to clopidogrel, the low dose
      prasugrel seems to be effective in keeping the percentage inhibition value of PRU
      within the normal range in treatment of cerebral aneurysm. Further study will be
      needed to determine the optimal dose of prasugrel to enhance prevention effect of
      thromboembolism and to reduce hemorrhagic complications during stent assisted
      coiling.

PMID- 30196684
TI  - Low-Dose Prasugrel in Treatment of Cerebral Aneurysms.

PMID- 30196685
TI  - First Human Evaluation of Endothelial Healing after a Pipeline Flex Embolization
      Device with Shield Technology Implanted in Posterior Circulation Using Optical
      Coherence Tomography.
AB  - A 64-year-old female presented with an incidentally-discovered right posterior
      inferior cerebral artery (PICA) aneurysm, initially treated in 2015 by simple
      coiling. Follow-up demonstrated significant coil compaction that required
      retreatment. Retreatment was done uneventfully using a Pipeline embolization
      device (PED) shield deployed starting from the basilar artery and ending at the
      V4 segment of the vertebral artery. Eight-weeks post-deployment, a follow-up
      digital subtraction imaging (DSA) and intravascular imaging with optical
      coherence tomography were obtained. The intravascular imaging demonstrated that
      the flow diverter had good wall apposition and concentric neointimal growth over
      the braid with exception to the areas that the PED was not in contact with the
      endothelial wall, such as at the right PICA ostium and at the vertebrobasilar
      junction. The entire procedure was safe, and the patient had no complications. In
      this article, we describe for the first time the assessment of the status of
      endothelial "healing" of the PED shield at 8-weeks.

PMID- 30196686
TI  - Internal Carotid Artery Reconstruction with a "Mega Flow Diverter": First
      Experience with the 6*50 mm DERIVO Embolization Device.
AB  - Endoluminal reconstruction with a flow diverter device has emerged as a viable
      and often preferable alternative to traditional techniques for the treatment of
      intracranial aneurysms. Precise measurement and device selection are mandatory
      steps when considering flow diverters usage in order to avoid potential
      complications. In this sense, incomplete wall-apposition has been described as a
      predictive factor for immediate in-stent and delayed thrombosis after stent use.
      One significant usage limitation of flow diverter devices is the parent artery
      diameter, since the maximum opening of the sizes available are recommended for
      vessel diameters between 5.2-5.75 mm. Here we present the first clinical use of
      the largest flow diverter available, the 6*50 mm DERIVO embolization device
      (Acandis GmbH & Co. KG, Pforzheim, Germany), into the arterial circulation for a
      cervical internal carotid artery endovascular reconstruction. This is a new
      device for large or fusiform aneurysms requiring flow diversion, especially
      located in the vertebrobasilar system or extracranial segments.

PMID- 30196687
TI  - Endovascular Treatment of Idiopathic Intracranial Hypertension with Stenting of
      the Transverse Sinus Stenosis.
AB  - For many years, the pathophysiology of idiopathic intracranial hypertension (IIH)
      was interpreted as "secondary intracranial hypertension," and IIH was considered
      to be caused by brain edema due to obstructive sleep apnea. Another theory
      proposed cerebrospinal fluid (CSF) absorption impairment due to excessive
      medication with vitamin A derivatives. Other reports pointed out the importance
      of obesity, which may cause an impairment of intracranial venous drainage due to
      elevated right atrial pressure. Patients with medically refractory IIH have
      traditionally undergone a CSF diversion. Venous outlet impairment on IIH has
      recently been reported as a causative or contributory cause, and thus focused
      venoplasty of the stenotic sinus with a stent has emerged as a new treatment
      strategy. We report the cases of two patients who presented with headache and
      papilledema with IIH. They successfully underwent stent placement at the stenosis
      of the transverse sinus and experienced complete resolution of symptoms.

PMID- 30196688
TI  - Robotic and Endoscopic Thyroid Surgery: Evolution and Advances.
AB  - To minimize surgical morbidity and neck scarring, minimally invasive
      thyroidectomy and robotic/endoscopic thyroidectomy via cervical, axillary,
      anterior chest, breast, postauricular or transoral approaches have been developed
      over the past 20 years. In this article, we review the evolution of robotic and
      endoscopic thyroid surgery and recent advances. Among remote access approaches,
      the gasless transaxillary approach, bilateral axillo-breast approach,
      postauricular facelift approach, and transoral vestibular approach are in common
      use today. Each procedure has its own advantages and disadvantages. Therefore, we
      need to understand these advantages and limitations, and to select the
      appropriate method for each patient. The most significant advantage of remote
      access thyroidectomy is its excellent cosmesis. The complication rate is similar
      in patients undergoing a remote access approach and those undergoing conventional
      surgery if the former is performed by experienced surgeons. Operative time is
      significantly longer in remote access thyroidectomy. In conclusion remote access
      thyroidectomy is feasible and its outcomes are comparable to those of
      conventional transcervical thyroidectomy in highly selected patients.

PMID- 30196689
TI  - Zygomatic implants in our daily practice. Part I: Treatment Plan and Surgical
      Technique
AB  - Prosthetic rehabilitation of the atrophic edentulous maxilla is a challenge for
      which zygomatic implants (ZI) stand out from traditional techniques (aiming to
      increase bone volume) with reduced treatment duration and immediate loading. The
      aim of this study was to review the ZI treatment plan and its surgical technique
      based on a series of nine edentulous atrophic maxillary cases. Implant survival
      rate and postoperative follow-up were reported as well as those described in the
      literature. The advantages and disadvantages of ZI versus traditional methods of
      rehabilitation in our daily work were also discussed. Implant survival rate was
      100% over follow-up periods varying from 5 to 47 months. During postoperative
      follow-up, two patients presented with slight palate inflammation. The results
      obtained with zygomatic implants are satisfactory in terms of reproducibility and
      speed of rehabilitation of the maxillary. When the patient wishes a fixed
      prosthetic rehabilitation, the solution provided by the ZI becomes more common in
      the daily practice of the clinician.

PMID- 30196690
TI  - Zygomatic implants in our daily practice. Part II: Prosthetic rehabilitation and
      effect on quality of life
AB  - Effect of prosthesis and dental implants on quality of life related to the
      patient's oral health can guide the clinician in providing best services. The
      zygomatic implant (ZI) is a partial or complete alternative technique to so
      called traditional rehabilitation techniques (aiming to increase bone volume) of
      edentulous atrophic maxillae. The objective of this study was to evaluate the
      impact of fixed prosthetic rehabilitation by ZI on patients' quality of life.
      This study highlighted the level of satisfaction of nine patients treated with ZI
      via their pre-therapeutic and post-therapeutic scores on the Oral Health Impact
      Profile (OHIP)-14 scale. Effect of ZI on quality of life in reference literature
      was also discussed. The mean pre-therapeutic and post-therapeutic OHIP scores
      were 29.1 and 5.8, respectively. Results about the quality of life of our
      patients was very satisfying. In accordance with literature, fixed prosthetic
      rehabilitation on ZI brought satisfaction in both its functional and aesthetic
      dimensions. This option of therapeutic arsenal for advanced atrophy of the
      edentulous maxillary is becoming more and more interesting in our daily practice.

PMID- 30196691
TI  - PRF in dentistry - a short synopsis about implementation and workflow
AB  - Platelet-rich fibrin (PRF) is a blood concentrate system derived from human
      peripheral blood. A solid and a liquid PRF-based matrix can be obtained by
      centrifugation in accordance with specific centrifugation protocols without the
      addition of anticoagulants or external chemicals. In dentistry, oral- and cranio
      maxillo-facial surgery, PRF-based matrices are used on different subjects. The
      healing benefits of platelet-rich preparations together with the low risk profile
      and disposability of a simple preparation procedure should encourage more
      clinicians to incorporate PRF as a treatment option in their practice to
      accelerate healing, reduce adverse events, and improve patient outcomes.

PMID- 30196692
TI  - Low Temperature Oxidation Kinetics of Biodiesel Molecules: Rate Rules for
      Concerted HO2 Elimination from Alkyl Ester Peroxy Radicals.
AB  - In an attempt to construct detailed kinetic mechanisms for biodiesel fuels on the
      fly, high-pressure rate rules for the concerted HO2 elimination reaction class
      were derived using a comprehensive training reaction set of more than 60
      reactions involving different alkyl methyl/ethyl ester peroxy radicals (RCOOR')
      OO*. Using the composite electronic structure method CBS-QB3 in combination with
      classical statistical mechanics and the transition state theory (TST) rate model,
      high-pressure rate constants for the reactions in the training set as well as
      thermodynamic properties for the species involved were calculated. The
      corrections from Eckart tunneling and hindered internal rotation (HIR) treatments
      were also included in the calculations. The results reveal that the ester group (
      COO-) selectively promotes the reaction when compared with the traditional
      hydrocarbon fuels; thus it is recommended that the seven derived rate rules for
      the title reaction class (including the thermodynamic data of the species
      involved in the NASA format) should be used for construction of detailed kinetic
      mechanisms for real biodiesel molecules.

PMID- 30196693
TI  - Quantitative Imaging of Specific Proteins in the Human Retina by Laser Ablation
      ICPMS using Bioconjugated Metal Nanoclusters as Labels.
AB  - A sensitive methodology using antibody-conjugated gold nanoclusters (AuNCs) was
      developed for the quantitative bioimaging of specific proteins in biological
      tissues by laser ablation (LA) coupled to inductively coupled plasma-mass
      spectrometry (ICPMS). Determination of metallothioneins (MT1/2 protein isoforms)
      images in human retina tissue sections was carried out as a proof of concept.
      AuNCs used as label were conjugated to the selected antibody through carbodiimide
      coupling. A stoichiometry of AuNCs/available antibody of 1:1 was obtained. The
      high amplification provided by AuNC labels allowed for obtaining the distribution
      of MT1/2 in the neurosensory retina layers (5 MUm thick sections) by LA-ICPMS.
      Elemental images of 197Au+ were quantified with gelatin matrix-matched standards
      and then converted to 2D quantitative images of MT1/2 concentration. For
      validation purposes, average concentrations of MT1/2 obtained in the human
      retinal layers by LA-ICPMS were successfully compared with those obtained with a
      commercial ELISA kit.

PMID- 30196694
TI  - Mitochondrial Peroxynitrite Mediation of Anthracycline-Induced Cardiotoxicity as
      Visualized by a Two-Photon Near-Infrared Fluorescent Probe.
AB  - Anthracyclines rank among the most efficacious anticancer medications. However,
      their clinical utility and oncologic efficacy are severely compromised by the
      cardiotoxicity risk facing the early-diagnosis difficulty and their unclear
      molecular mechanism. Herein, a two-photon-excitable and near-infrared-emissive
      fluorescent probe, TPNIR-FP, was fabricated and endowed with extraordinary
      specificity and sensitivity and a rapid response toward peroxynitrite (ONOO-), as
      well as mitochondria-targeting ability. With the aid of TPNIR-FP, we demonstrate
      that mitochondrial ONOO- is upregulated in the early stage and contributes to the
      onset and progression of anthracycline cardiotoxicity in cardiomyocyte and mouse
      models; therefore, it represents an early biomarker to predict subclinical
      cardiotoxicity induced by drug challenge. Furthermore, TPNIR-FP is proved to be a
      robust imaging tool to provide critical insights into drug-induced cardiotoxicity
      and other ONOO--related pathophysiological processes.

PMID- 30196695
TI  - Acrylamide Defects the Expression Pattern of the Circadian Clock and
      Mitochondrial Dynamics in C57BL/6J Mice Liver and HepG2 Cells.
AB  - Circadian rhythm helps organisms adapt to their environment and control a variety
      of physiological and metabolic processes. Acrylamide is a toxic compound that can
      be produced during food processing. The aim of this research is to investigate
      whether the circadian clock is involved in the toxicity mechanisms of acrylamide
      in mice liver. Our results revealed that acrylamide markedly induced circadian
      gene oscillation disorder and blocked circadian-related protein in mice liver and
      HepG2 cells. Simultaneously, the balance of the daily oscillation of the
      antioxidant enzymes was impeded under acrylamide treatment. Furthermore,
      acrylamide treatment elevated the mitochondrial dynamic gene expressions and
      influenced the mitochondrial morphology at the night phase. Acrylamide blocked
      circadian protein expression via repressing the phosphorylation of AKT or
      inducing oxidative stress. Taken together, our work reveals acrylamide as a clock
      repressing compound generated through the Maillard browning reaction in certain
      foods that may possess a toxic effect via circadian clock mechanisms.

PMID- 30196696
TI  - Effects of Amphipathic Polypeptides on Membrane Organization Inferred from
      Studies Using Bicellar Lipid Mixtures.
AB  - SP-B63-78, a lung surfactant protein fragment, and magainin 2, an antimicrobial
      peptide, are amphipathic peptides with the same overall charge but different
      biological functions. Deuterium nuclear magnetic resonance has been used to
      compare the interactions of these peptides with dispersions of 1,2-dimyristoyl-
      sn-glycero-3-phophocholine (DMPC)/1,2-dihexanoyl- sn-glycero-3-phophocholine
      (DHPC) (4:1) and DMPC/1,2-dimyristoyl- sn-glycero-3-phopho-(1'-rac-glycerol)
      (DMPG)/DHPC (3:1:1), two mixtures of long-chain and short-chain lipids that
      display bicellar behavior. This study exploited the sensitivity of a bicellar
      system structural organization to factors that modify partitioning of their lipid
      components between different environments. In small bicelle particles formed at
      low temperatures, short-chain components preferentially occupy curved rim
      environments around bilayer disks of the long-chain components. Changes in chain
      order and lipid mixing, on heating, can drive transitions to more extended
      assemblies including a magnetically orientable phase at intermediate temperature.
      In this work, neither peptide had a substantial effect on the behavior of the
      zwitterionic DMPC/DHPC mixture. For bicellar mixtures containing the anionic
      lipid DMPG, the peptide SP-B63-78 lowered the temperature at which magnetically
      orientable particles coalesced into more extended lamellar structures. SP-B63-78
      did not promote partitioning of the zwitterionic and anionic long-chain lipid
      components into different environments. Magainin 2, on the other hand, was found
      to promote separation of the anionic lipid, DMPG, and the zwitterionic lipid,
      DMPC, into different environments for temperatures above 34  degrees C. The
      contrast between the effects of these two peptides on the lipid mixtures studied
      appears to be consistent with their functional roles in biological systems.

PMID- 30196697
TI  - Modulation of Water Vapor Sorption by a Fourth-Generation Metal-Organic Material
      with a Rigid Framework and Self-Switching Pores.
AB  - Hydrolytically stable adsorbents are needed for water vapor sorption related
      applications; however, design principles for porous materials with tunable water
      sorption behavior are not yet established. Here, we report that a platform of
      fourth-generation metal-organic materials (MOMs) with rigid frameworks and self
      switching pores can adapt their pores to modulate water sorption. This platform
      is based upon the hydrolytically stable material CMOM-3S, which exhibits bnn
      topology and is composed of rod building blocks based upon S-mandelate ligands,
      4,4-bipyridine ligands, and extraframework triflate anions. Isostructural
      variants of CMOM-3S were prepared using substituted R-mandelate ligands and
      exhibit diverse water vapor uptakes (20-67 cm3/g) and pore filling pressures ( P/
      P0, 0.55-0.75). [Co2( R-4-Cl-man)2(bpy)3](OTf) (33R) is of particular interest
      because of its unusual isotherm. Insight into the different water sorption
      properties of the materials studied was gained from analysis of in situ
      vibrational spectra, which indicate self-switching pores via perturbation of
      extraframework triflate anions and mandelate linker ligands to generate
      distinctive water binding sites. Water vapor adsorption was studied using in situ
      differential spectra that reveal gradual singlet water occupancy followed by
      aggregation of water clusters in the channels upon increasing pressure. First
      principles calculations identified the water binding sites and provide structural
      insight on how adsorbed water molecules affect the structures and the binding
      sites. Stronger triflate hydrogen bonding to the framework along with significant
      charge redistribution were determined for water binding in 33R. This study
      provides insight into a new class of fourth-generation (self-switching pores) MOM
      and the resulting effect upon water vapor sorption properties.

PMID- 30196698
TI  - Aroma Compounds in Chicken Broths of Beijing Youji and Commercial Broilers.
AB  - The unique flavor of Beijing Youji (BJY) chicken broth compared with that of
      commercial broilers (CB) was investigated by solvent-assisted flavor evaporation
      combined with AEDA/GC-O (aroma extract dilution analysis of gas chromatography
      olfactometry), quantitation, and aroma recombination. A total of 71 odorants with
      almost the same major odorants (>=10 ng/g broth) were found by GC-O in both BJY
      and CB broths. However, BJY broth had thirty-two more extra odorants than CB
      broth, indicating the rich fragrance of the former. Aroma recombination and
      omission experiments demonstrated that 21 versus 17 odorants (with OAV >= 1)
      contributed significantly to BJY and CB broth aromas, respectively. Those key
      odorants mainly included sulfur-containing compounds and aliphatic aldehydes,
      such as 2-methyl-3-furanthiol, 3-(methylthio)propanal, ( E, E)-2,4-decadienal,
      etc. Furthermore, composition analysis of the meat suggested that the better
      flavor, with rather more odorants, of BJY broth is probably due to higher
      contents of polyunsaturated fatty acids and water-soluble flavor precursor,
      including ribose, cysteine, thiamine, etc., present in the BJY meat.

PMID- 30196699
TI  - Reversible Control of Protein Localization in Living Cells Using a Photocaged
      Photocleavable Chemical Dimerizer.
AB  - Many dynamic biological processes are regulated by protein-protein interactions
      and protein localization. Experimental techniques to probe such processes with
      temporal and spatial precision include photoactivatable proteins and chemically
      induced dimerization (CID) of proteins. CID has been used to study several
      cellular events, especially cell signaling networks, which are often reversible.
      However, chemical dimerizers that can be both rapidly activated and deactivated
      with high spatiotemporal resolution are currently limited. Herein, we present a
      novel chemical inducer of protein dimerization that can be rapidly turned on and
      off using single pulses of light at two orthogonal wavelengths. We demonstrate
      the utility of this molecule by controlling peroxisome transport and mitotic
      checkpoint signaling in living cells. Our system highlights and enhances the
      spatiotemporal control offered by CID. This tool addresses biological questions
      on subcellular levels by controlling protein-protein interactions.

PMID- 30196700
TI  - Two-Step to One-Step Nucleation of a Zeolite through a Metastable Gyroid
      Mesophase.
AB  - The importance of nonclassical nucleation pathways in the formation of complex
      crystals has become apparent in recent years. Nonclassical pathways were
      unraveled for, among others, the crystallization of proteins, colloids, and
      clathrates. In those cases, the formation of a metastable fluid with density
      close to the crystal decreases the crystallization barrier. Recent simulations
      indicate that mesophases can facilitate the nucleation of zeolites. Here, we use
      molecular simulations to investigate the role of a gyroid mesophase on the
      crystallization of a model zeolite from liquid. The nucleation pathway is always
      nonclassical. At warmer temperatures, the mechanism proceeds in two well-defined
      steps: nucleation of a metastable gyroid followed by its crystallization into a
      zeolite. At colder temperatures, the second barrier becomes negligible, and the
      crystallization occurs in one step. This second scenario is also nonclassical, as
      the critical nucleus for the crystallization has the structure of the gyroid and
      seamlessly transforms into a zeolite as it grows past its critical size. To our
      knowledge, this is the first report of a nonclassical mechanism of
      crystallization mediated by a mesophase.

PMID- 30196701
TI  - Ajothiolanes: 3,4-Dimethylthiolane Natural Products from Garlic ( Allium
      sativum).
AB  - Stereoisomers of 5-(2-allylsulfinyl)-3,4-dimethylthiolane-2-ol, a family of 3,4
      dimethylthiolanes of formula C9H16O2S2 we name ajothiolanes, were isolated from
      garlic ( Allium sativum) macerates and characterized by a variety of analytical
      and spectroscopic techniques, including ultraperformance liquid chromatography
      (UPLC), direct analysis in real time-mass spectrometry (DART-MS), and liquid
      chromatography-tandem mass spectrometry (LC-MS/MS). Ajothiolanes were found to be
      spectroscopically identical to a family of previously described compounds named
      garlicnins B1-4 (C9H16O2S2), whose structures we demonstrate have been
      misassigned. 2D 13C-13C NMR incredible natural abundance double quantum transfer
      experiments (INADEQUATE) were used to disprove the claim of nine contiguous
      carbons in these compounds, while X-ray absorption spectroscopy (XAS) along with
      computational modeling was used to disprove the claim that these compounds were
      thiolanesulfenic acids. On the basis of the similarity of their NMR spectra to
      those of the ajothiolanes, we propose that the structures of previously
      described, biologically active onionins A1-3 (C9H16O2S2), from extracts of onion
      ( Allium cepa) and Allium fistulosum, and garlicnin A (C12H20O2S4), from garlic
      extracts, should also be reassigned, in each case as isomeric mixtures of 5
      substituted-3,4-dimethylthiolane-2-ols. We conclude that 3,4-dimethylthiolanes
      may be a common motif in Allium chemistry. Finally, we show that another garlic
      extract component, garlicnin D (C7H12O2S3), claimed to have an unprecedented
      structure, is in fact a known compound from garlic with a structure different
      from that proposed, namely, 2( E)-3-(methylsulfinyl)-2-propenyl 2-propenyl
      disulfide.

PMID- 30196702
TI  - The C 1Bu <- X 1Sigmag+ Transition of Ethanedinitrile (C2N2): Assignment of the
      Electronic State Origin and Vibrational Bands.
AB  - An analysis is presented for the vacuum ultraviolet C2N2 C1Bu <- X1Sigmag+
      transition. Contrary to previous assumptions this is found to be a linear to bent
      transition with a trans-bent C1Bu excited electronic state. The band origin is at
      59 840 cm-1. Vibrational bands between 170 and 145 nm are assigned. Vibrational
      frequencies for the C1Bu state are found to be nu1 = 2055 +/- 20 cm-1 for the
      symmetric CN stretch, nu2 = 979 +/- 20 cm-1 for the symmetric CC stretch, nu3 =
      542 +/- 10 cm-1 for the trans-bend, nu4 = 131 +/- 10 cm-1 for the out-of-plane
      torsional bend, and nu6 = 141 +/- 10 cm-1 for the cis-bend.

PMID- 30196703
TI  - Digestive-Ripening-Facilitated Nanoengineering of Diverse Bimetallic
      Nanostructures.
AB  - From an ingenious methodology for obtaining monodispersity, digestive ripening
      has advanced to become an outstanding solution-based synthesis route to realizing
      various bimetallic heterostructures. This feature article attempts to provide an
      overview of the various facets of the codigestive ripening process and the array
      of heterostructures that could be achieved by this technique. We briefly discuss
      the mechanism of digestive ripening in the case of monometallic elements and use
      that understanding to elucidate the mechanism of the less well established
      codigestive ripening strategy for designing bimetallic nanostructures. The
      systems studied by our group in the past decade for the fabrication of diverse
      heterostructures are highlighted in this article. The exploitation of digestive
      ripening to realize monodisperse bimetallic nanostructures by several other
      groups is also featured. In addition to digestive ripening agents, the
      significance of tuning various reaction parameters and its consequences on the
      final structure and morphology have also been discussed. Additionally, efforts
      based on theoretical studies to gain insight into the factors which dominate the
      mechanism of the digestive ripening process have also been covered. This article
      is a contribution to the understanding of the codigestive ripening methodology
      and a demonstration of its tremendous potential in achieving the desired
      bimetallic heteronanostructures.

PMID- 30196704
TI  - ( R)- N-(1-Methyl-2-hydroxyethyl)-13-( S)-methyl-arachidonamide (AMG315): A Novel
      Chiral Potent Endocannabinoid Ligand with Stability to Metabolizing Enzymes.
AB  - The synthesis of potent metabolically stable endocannabinoids is challenging.
      Here we report a chiral arachidonoyl ethanolamide (AEA) analogue, namely, (13
      S,1' R)-dimethylanandamide (AMG315, 3a), a high affinity ligand for the CB1
      receptor ( Ki of 7.8 +/- 1.4 nM) that behaves as a potent CB1 agonist in vitro
      (EC50 = 0.6 +/- 0.2 nM). (13 S,1' R)-dimethylanandamide is the first potent AEA
      analogue with significant stability for all endocannabinoid hydrolyzing enzymes
      as well as the oxidative enzymes COX-2. When tested in vivo using the CFA-induced
      inflammatory pain model, 3a behaved as a more potent analgesic when compared to
      endogenous AEA or its hydrolytically stable analogue AM356. This novel analogue
      will serve as a very useful endocannabinoid probe.

PMID- 30196705
TI  - Experience of receiving care by interns reduces psychological barrier of
      community residents to further care in Japan.
AB  - INTRODUCTION: A uniform certified basic training program for interns started in
      Japan in 2004. Following this change, more interns chose to train in community
      settings, including in rural areas. Patients' experiences of and attitudes toward
      interns' practice might vary across communities. To examine the geographic and
      demographic variations linked to the new training system, a nationwide cross
      sectional survey was conducted and analyzed. METHODS: Two years after the start
      of the new certified basic program, 2400 adults were randomly selected from all
      areas of Japan. Those who participated were asked about their experiences of and
      attitudes toward interns' practice. The data were used to compare differences in
      geographic areas and by demographic factors. RESULTS: A total of 1109 (46%)
      people participated in the study. Of these, 10% (114/1109) had been treated by
      interns. In total, 37% (410/1084) of respondents were prepared to accept
      treatment from interns. Those with personal experience of receiving treatment
      from an intern were significantly more likely to be comfortable with the idea
      than those who had no personal experience (55%, p<0.001). This acceptance level
      did not vary by region or population (between urban and rural areas). People who
      were comfortable with interns providing treatment, and who had personal
      experience of care provision by interns (they or a family member had done so)
      were more likely to understand the importance of interns being able to practice
      as part of their clinical training (92% (p<0.001) vs 76% (p=0.006)). They were
      also more likely to believe that interns should be able to receive training at
      smaller hospitals (76% (p<0.001) vs 77% (p=0.02)). CONCLUSIONS: Acceptance by
      patients of interns' practice was positively associated with experience of care
      provision by interns. However, there was no significant difference of acceptance
      among geographic conditions, and among the size of population. Community-based
      medical education could be implemented and developed independent of geographic
      and demographic elements in Japan.

PMID- 30196706
TI  - A Guide to Evaluation of Quality Improvement and Patient Safety Educational
      Programs: Lessons From the VA Chief Resident in Quality and Safety Program.
AB  - With the recent proliferation of quality improvement (QI) and patient safety (PS)
      education programs, guidance is needed on how to assess the effectiveness of
      these programs. Without a systematic approach, evaluation efforts may end up
      being disjointed, lead to excess participant burden, or yield unhelpful feedback
      because of poor fit with program priorities. This article presents a framework
      for developing a multilevel evaluation infrastructure using examples from the
      evaluation of the national Department of Veterans Affairs Chief Resident in
      Quality and Safety program, a 1-year, post-accreditation program to develop
      leadership and teaching skills in QI and PS. It illustrates how to apply the
      framework to establish evaluation priorities and methods, and shares sample
      results and how they are used to guide program improvements and track important
      outcomes at multiple levels. The framework is particularly relevant to other
      nonaccredited advanced QI/PS programs, yet offers useful considerations for
      evaluating any advanced medical education program.

PMID- 30196707
TI  - Interactive effects of alpha-tocopheryl acetate and zinc supplementation on the
      antioxidant and immune systems of broilers.
AB  - 1. A total of 1440 one-day-old Ross 308 male broilers were allocated to 12
      dietary treatments to evaluate dose-dependent effects of alpha-tocopheryl acetate
      (alpha-TOA) combined with zinc (Zn) supplementation on humoral and cellular
      immune responses, antioxidant enzymes, serum and hepatic contents of vitamins and
      minerals in broilers. 2. Three levels of supplemental alpha-TOA (0, 150 and 300
      mg/kg) and 4 levels of Zn (0, 100, 200 and 400 mg/kg) were combined as a
      completely randomised design as a 3 * 4 factorial arrangement. 3. Concentrations
      of serum alpha-tocopherol and selenium were influenced by the interaction of
      alpha-TOA and Zn. The interaction of alpha-TOA and Zn affected malondialdehyde
      (MDA) concentration in serum and liver (p < 0.05). Incremental amounts of
      supplemental Zn augmented the effects of alpha-TOA in reducing serum and hepatic
      MDA concentrations. 4. The interaction of alpha-TOA and Zn on antibody titres (p
      < 0.05) was such that increasing level of Zn at each alpha-TOA level led to a
      linear enhancement in antibody titre. Moreover, dietary supplementation with
      alpha-TOA and Zn resulted in an increase in relative weight of lymphoid organs
      (thymus, bursa, spleen; p < 0.05) along with an increase in humoral and cellular
      immune responses (p < 0.05). 5. In conclusion, alpha-TOA with Zn showed
      interactive effects in improving oxidative stability and humoral immune
      responses, which could result from their impact on the concentrations of
      antioxidant vitamins and minerals in tissues.

PMID- 30196709
TI  - Taking the Patient Out of Patient-Centered Care?

PMID- 30196708
TI  - Changes in Care After Implementing a Multifaceted Intervention to Improve
      Preventive Cardiology Practice in Rheumatoid Arthritis.
AB  - Rheumatoid arthritis (RA) increases cardiovascular disease (CVD) risk. However,
      CVD risk factor identification and treatment is often inadequate. The authors
      implemented a multifaceted rheumatology practice intervention to improve CVD risk
      factor measurement, assessment, and management. The intervention included
      clinician education, point-of-care decision support, feedback, and care
      management. The authors measured quality indicators from electronic health
      records and assessed impact with interrupted time series. Following the
      intervention, more RA patients had all major CVD risk factors assessed (53% vs
      72.2%), and the rate of increase was greater during the intervention period than
      baseline (difference of 0.74% per month, P = .0016). Moderate- or high-intensity
      statin prescribing increased (21.6% to 28.2%), but the rate of change was not
      different from baseline. Several other quality measures did not increase.
      Although CVD risk factor assessment improved, the intervention did not affect
      risk factor management and control. Other strategies are needed to optimize CVD
      prevention in RA.

PMID- 30196710
TI  - Feeding broilers with thyme essential oil loaded in chitosan nanoparticles: an
      efficient strategy for successful delivery.
AB  - 1. The use of chitosan nanoparticles (CNPs) for the entrapment of active
      components has gained considerable interest in food and pharmaceutical industries
      due to its mucous adhesiveness, non-toxicity, biocompatibility and
      biodegradability. 2. This study aimed to investigate the usefulness of feeding
      encapsulated thyme essential oil (E-TEO) on performance, blood parameters,
      immunity and ileal microflora in broilers. 3. CNPs were prepared by using
      ionotropic gelation and structurally characterised by dynamic light scattering;
      scanning electron microscope and Fourier transform infrared spectroscopy. The
      encapsulation efficiency percentage of TEO in CNPs and its in vitro release were
      determined using ultraviolet visible spectroscopy and dialysis method,
      respectively. 4. An in vivo experiment was conducted with five treatments of five
      replicates with ten chicks per pen. Dietary treatments consisted of an
      unsupplemented control diet, or supplemented with chlortetracycline (80 and 50
      mg/kg during the starter and grower phase, respectively); CNPs (60 mg/kg); TEO
      (40 mg/kg diet) or E-TEO (60 mg/kg). 5. Results showed uniform distribution of
      nanoparticles with roughly spherical morphology, and the size of particles ranged
      from 30 to 100 nm. It was observed that 68.3% of TEO was encapsulated into CNPs,
      from which more than 90% was released within the first 96 h. Birds treated with
      antibiotic and E-TEO showed significantly (P < 0.05) higher body weight gain than
      the control and the other treatments were intermediate. Compared to the control
      group, adding of E-TEO into diet significantly (P < 0.05) improved feed
      conversion ratio at 42 days of age. Feeding birds with E-TEO significantly (P <
      0.05) decreased the number of coliform and total aerobic bacteria compared to
      other treatments. Birds supplemented with E-TEO showed lower heterophile to
      lymphocyte ratio compared to birds that received TEO. 6. The results suggested
      that the entrapment of TEO in CNPs and its sustained release promoted broiler
      performance via the improvement of physiological status and modulating intestinal
      microbiota and therefore could be used as substitute for antibiotic growth
      promoter in broiler diets.

PMID- 30196711
TI  - Lessons Learned in Providing Claims-Based Data to Participants in Health Care
      Innovation Models.
AB  - The Centers for Medicare & Medicaid Services (CMS) has been providing data to
      organizations participating in a range of innovation models to help them
      implement interventions and to provide feedback on performance. The authors
      studied 18 CMS models to gain a better understanding of factors contributing to
      model participants' use or nonuse of CMS-provided data. Factors that contribute
      to greater use include providing data that participants view as actionable, some
      type of accountability for performance, robust learning support, participants
      having resources to work with the data, and soliciting ongoing feedback about the
      data and related learning needs. Factors that discourage data uptake include time
      lag, lack of aggregated multi-payer data, exclusion of data for sensitive
      diagnoses, and small sample sizes. Claims-based data from payers can be an
      important source of information to innovation model participants. Lessons from
      this study can increase the usefulness of such data.

PMID- 30196712
TI  - Impact of Hearing Loss on Patient-Provider Communication Among Hospitalized
      Patients: A Systematic Review.
AB  - Age-related hearing loss is a highly prevalent chronic condition in older adults,
      but hearing loss is rarely accounted for in patient-provider communication
      studies. This systematic review synthesizes current evidence on the impact of age
      related hearing loss on patient-provider communication in hospitalized older
      adults. Five databases were queried to identify original research that examined
      patient-provider communication in older adults with hearing loss in an inpatient
      setting. Of 1053 studies, 13 were included in the final review. All studies
      reported an adverse effect of hearing loss on patient-provider communication.
      Among studies that evaluated an intervention to improve communication in older
      adults with hearing loss, simple interventions such as low-cost voice amplifiers
      were found to improve communication. An understanding of the effect of hearing
      loss on patient-provider communication and strategies to mitigate the impact are
      needed in order to provide safe, quality, patient-centered care to older adults
      with hearing loss.

PMID- 30196713
TI  - BRAFi/MEKi in patients with metastatic melanoma: predictive factors of complete
      response.
AB  - AIM: A survival benefit was demonstrated by dabrafenib + trametinib for
      metastatic BRAF-mutated melanoma patients. Best response is a strong prognostic
      marker for survival. PATIENTS & METHODS: The specific features associated with
      complete response (CR) were evaluated. RESULTS: A total of 15/66 patients
      achieved CR. Median size of lesions was 3 cm (range: 0.5-10). Using that value as
      cut-off, the CR rate was 39.3% in patients with smaller lesions and 10.5% in
      patients with bigger size (p = 0.006). The clinical features associated with CR
      were the number of metastatic sites and the largest diameter of the biggest
      metastatic site. CONCLUSION: The number of the metastases and the diameter of the
      largest metastatic site are associated with a higher CR rate.

PMID- 30196714
TI  - [A new era of transfusion-transmitted pathogens, infections. Renewed need for
      updating standards for clinicans along with blood banking].
AB  - Preparative and clinical transfusiology and transfusion, a majestic part of
      clinical medicine saved the life of hundred millions. However, bloodborne or
      transmitted infections became a serious issue in France in the 1980s, when many
      haemophiliacs were infected by HIV or hepatitis C virus by receiving plazma
      FactorVIII concentrates. This resulted in a quick and powerful development of
      screening as well as pathogen-inactivating methods, which reduced pathogen
      contamination and transmission to minimal levels. Times and pathogens are
      continously and rather quickly changing, so during the last decade many - not
      only egzotic - new pathogens and diseases were recognised, and some of them
      (e.g., Zyka virus, Ebola, hepatitis E virus, etc.) can also be transmitted by
      blood or blood-component transfusions, and in some instances they escape from
      standard screening and inactivation procedures. Hereby we try to focus and draw
      attention to some of these potentially pathogenic new bloodborne microbiological
      agents, and along with this we try to emphasize the significance of application
      of updated next generation screening and inactivation procedures. Interestingly a
      recent British trial, based on large population data, showed some evidence of a
      slight increase of non-Hodgkin lymphoma incidence in patients with multiple
      previous transfusions. Probably these facts are even more important in
      haemophiliacs, who receive prophylactic treatment 3 times weekly either by plasma
      factor concentrates derived from multiple donors or by gene synthetic factor
      sources. It is important that haemophiliac patient and family should receive the
      necessary information, and go for a fully informed consent based on the potential
      advantages and hazards of a particular treatment modality, the same way as in the
      chronic treatment of other diseases. Orv Hetil. 2018; 159(37): 1495-1500.

PMID- 30196715
TI  - [The spontaneous recanalization of the internal carotid artery. Case report].
AB  - The occlusion of the internal carotid artery (ICA) frequently leads to stroke and
      develops most commonly as a consequence of embolism or atherosclerotic
      thrombosis. Following acute care, if the patient's general condition makes it
      possible, the patient is usually emitted from the hospital or, if necessary, his
      treatment continues in the rehabilitation department. The occlusion is generally
      considered irreversible, but a regular duplex ultrasonographic (sometimes CT
      angiographic) check of the patient is required. According to recent literature,
      spontaneous recanalization of the ICA may occur occasionally. The authors
      demonstrated by evaluating a local case that ICA occlusion is not necessarily
      permanent: through a case of a 67-year-old man, who suffered a right ICA
      occlusion, subsequent ichaemic stroke, then spontaneous recanalization of the
      occlusion allowing a successful endarterectomy later on, they overview the
      literature and propose appropriate prospective examinations to track patents with
      similar conditions. Orv Hetil. 2018; 159(37): 1525-1528.

PMID- 30196717
TI  - [The effect of alternating meteorological parameters on fatally ruptured aortic
      aneurysms (autopsy-based data)].
AB  - INTRODUCTION: There are several statements about the connection between
      cardiovascular diseases and climate change. On behalf of our observation-based
      knowledge we hypothesized a relationship between the occurence of aortic aneurysm
      (AA) rupture and weather changes. AIM: The purpose of our study was to explore
      the relationship between fatal aortic catastrophe and changes in atmospheric
      pressure and temperature. By using a new method we could even measure the
      intensity of the connection. METHOD: We have developed a software earlier to
      examine the link between pulmonary embolism mortality and the weather on data
      sets comprised of aortic aneurysm cases, where the medical condition had led to
      the fatal rupture of the aorta. For the events mentioned earlier we used the
      autopsy database of Semmelweis University between January 1, 2005 and January 1,
      2014. Altogether we examined 152 aneurysm-related aortic catastrophes. We
      reported the exact day of the incident and the weather conditions on that day and
      the day before. RESULTS AND CONCLUSION: We have defined that the occurrence rate
      of fatal aortic catastrophe showed a slight dependence on the two examined
      parameters within our groups. We have found the connection related to ruptured
      aortic aneurysm and changes in atmospheric pressure more significant than their
      connection with mean daily temperatures. With the increase in atmospheric
      pressure, the rate of AA mortality also increased. In the knowledge of our
      results we believe that the mathematical model we used can be an effective
      starting point for population-based and prospective studies. Orv Hetil. 2018;
      159(37): 1501-1505.

PMID- 30196718
TI  - [A clinicopathological retrospective epidemiological analysis of benign tumors
      and tumor-like lesions in the oral and maxillofacial region, diagnosed at the
      University of Szeged, Department of Oral Medicine (1960-2014)].
AB  - INTRODUCTION: In a clinicopathological retrospective epidemiological study we
      investigated benign tumors and tumor-like lesions located in the orofacial
      region, diagnosed at the Universiy of Szeged, Department of Oral Medicine.
      METHOD: During a 54-year period (1960-2014), 14 661 biopsies were taken. The
      included subjects were 7491 patients diagnosed with benign tumors and tumor-like
      lesions. RESULTS: The average age of patients was 55.3 years, 2823 (37.7%)
      patients were male and 4668 (62.3%) female. The male : female ratio was 1 : 1.65.
      Most of the patients included in the study were aged 51-60 (1280, 17.1%). The
      number of children was 1014 (13.6%) and the number of adults was 6477 (86.3%).
      The number of non-neoplasms was 6420 (85.7%), being significantly higher than the
      number of neoplasms (1071, 14.3%). Most of the lesions were of mesenchymal origin
      (5574, 77.4%); the number of lesions of non-mesenchymal origin was 982 (13.1%).
      The most prevalent type of lesions was traumatic fibroma (fibrosis): 1806
      (32.4%). The most common lesion type in the group of lesions of
      infectious/inflammational origin was pyogenic granuloma, the number of which was
      465 (8.3%). The most common cystic lesion was mucocele (805, 10.7%). Hemangioma
      was the most frequent lesion type among developmental anomalies with the number
      of 815 (14.6%). The most common location of the lesions was the lip in 2081 cases
      (27.8%), followed by the gingiva in 2024 cases (27.0%), bucca in 1069 cases
      (14.3%), tongue in 981 cases (13.1%), and the facial skin in 695 cases (9.3%).
      After taking biopsy, the majority of benign lesions were treated with cryo-,
      laser-, or combined (cryo and laser) surgery. CONCLUSION: The present computer
      aided study showed that irritational fibroma was the most common orofacial benign
      tumor, and the lip was the most frequent location. The diagnostic classification
      and the methodology are considerably different in the majority of the studies,
      which may hinder the exact comparison with other surveys from different regions
      of the world. Orv Hetil. 2018; 159(37): 1516-1524.

PMID- 30196720
TI  - Improving Patient-Provider Communication and Therapeutic Practice Through Better
      Integration of Electronic Health Records in the Exam Room: A Pilot Study.
AB  - BACKGROUND: The rapid proliferation of electronic health records (EHRs) in
      clinics has had mixed impact on patient-centered communication, yet few evaluated
      interventions exist to train practicing providers in communication practices.
      AIMS: We extended the evidence-based Physician Asthma Care Education (PACE)
      program with EHR-specific communication strategies, and tested whether training
      providers with the extended program (EHR-PACE) would improve provider and patient
      perceptions of provider communication skills and asthma outcomes of patients.
      METHOD: A pilot randomized design was used to compare EHR-PACE with usual care.
      Participants were providers ( n = 18) and their adult patients with persistent
      asthma ( n = 126). Outcomes were assessed at baseline and 3- and 6-month
      postintervention, including patient perception of their provider's communication
      skills and provider confidence in using EHRs during clinical encounters. RESULTS:
      Compared with the control group, providers who completed the EHR-PACE program
      reported significant improvements at 3-month follow-up in their confidence with
      asthma counseling practices (estimate 0.90, standard error [ SE] 0.4); p < .05)
      and EHR-specific communication practices (estimate 2.3, SE 0.8; p < .01), and at
      6-month follow-up, a significant decrease in perception that the computer
      interferes with the patient-provider relationship (estimate -1.0, SE 0.3; p <
      .01). No significant changes were observed in patient asthma outcomes or their
      perception of their provider's communication skills. DISCUSSION: Training
      providers with skills to accommodate EHR use in the exam room increases provider
      confidence and their perceived skills in maintaining patient-centered
      communications in the short term. CONCLUSION: Evidence-supported training
      initiatives that can increase capacity of busy providers to manage increased
      computing demands shows promise. More research is needed to fully evaluate EHR
      PACE on patients' health status and their perceptions of their provider's care
      through a large-scale trial.

PMID- 30196719
TI  - [The role of endoscopy registries in quality health care. The first data from the
      Hungarian Endoscopic Retrograde Cholangiopancreatography (ERCP) Registry].
AB  - INTRODUCTION: The continuous monitoring of quality indicators in gastrointestinal
      endoscopy has become an essential requirement nowadays. Most of these data cannot
      be extracted from the currently used free text reports, therefore a structured
      web-based data-collecting system was developed to record the indicators of
      pancreatobiliary endoscopy. AIM: A structured data-collecting system, the ERCP
      Registry, was initiated to monitor endoscopic retrograde cholangiopancreatography
      (ERCP) examinations prospectively, and to verify its usability. METHOD: From
      January 2017, all ERCPs performed at the First Department of Medicine, University
      of Pecs, have been registered in the database. In the first year, the detailed
      data of 595 examinations were entered into the registry. After processing these
      data, the testing period of the registry is now finished. RESULTS: On 447
      patients, 595 ERCPs were performed. The success rate of cannulation is 93.8% if
      all cases are considered. Difficult biliary access was noted in 32.1% of patients
      with native papilla, and successful cannulation was achieved in 81.0% of these
      cases during the first procedure. Post-ERCP pancreatitis was observed in 13 cases
      (2.2%), clinically significant post-papillotomy bleeding was registered in 2
      cases (0.3%), while 27 patients (4.5%) developed temporary hypoxia during the
      procedure. 30-day follow-up was successful in 75.5% of the cases to detect late
      complications. All of the quality indicators determined by the American Society
      of Gastrointestinal Endoscopy (ASGE) were possible to monitor with the help of
      the registry. Our center already complies with most of these criteria.
      CONCLUSIONS: Continuous monitoring of the quality indicators of endoscopic
      interventions are not supported by the current hospital information system but it
      became possible with our registry. The ERCP Registry is a suitable tool to detect
      the quality of patient care and also useful for clinical research. Several
      endoscopy units have joined already this initiative and it is open for further
      centres through our web page ( https://tm-centre.org/hu/regiszterek/ercp
      regiszter/ ). Orv Hetil. 2018; 159(37): 1506-1515.

PMID- 30196721
TI  - Biologic bases of residual risk of cardiovascular events: A flawed concept.

PMID- 30196722
TI  - The envirome and coronary atherosclerosis: The role of socioeconomic conditions.

PMID- 30196723
TI  - Blue light exposure decreases systolic blood pressure, arterial stiffness, and
      improves endothelial function in humans.
AB  - AIMS: Previous studies have shown that ultraviolet light can lead to the release
      of nitric oxide from the skin and decrease blood pressure. In contrast to visible
      light the local application of ultraviolet light bears a cancerogenic risk. Here,
      we investigated whether whole body exposure to visible blue light can also
      decrease blood pressure and increase endothelial function in healthy subjects.
      METHODS: In a randomised crossover study, 14 healthy male subjects were exposed
      on 2 days to monochromatic blue light or blue light with a filter foil (control
      light) over 30 minutes. We measured blood pressure (primary endpoint), heart
      rate, forearm vascular resistance, forearm blood flow, endothelial function (flow
      mediated dilation), pulse wave velocity and plasma nitric oxide species, nitrite
      and nitroso compounds (secondary endpoints) during and up to 2 hours after
      exposure. RESULTS: Blue light exposure significantly decreased systolic blood
      pressure and increased heart rate as compared to control. In parallel, blue light
      significantly increased forearm blood flow, flow-mediated dilation, circulating
      nitric oxide species and nitroso compounds while it decreased forearm vascular
      resistance and pulse wave velocity. CONCLUSION: Whole body irradiation with
      visible blue light at real world doses improves blood pressure, endothelial
      function and arterial stiffness by nitric oxide released from photolabile
      intracutanous nitric oxide metabolites into circulating blood.

PMID- 30196724
TI  - Diastolic left ventricular function in relation to circulating metabolic
      biomarkers in a population study.
AB  - Aims We studied the association of circulating metabolic biomarkers with
      asymptomatic left ventricular diastolic dysfunction, a risk-carrying condition
      that affects 25% of the population. Methods and results In 570 randomly recruited
      people, we assessed in 2005-2010 and in 2009-2013 the multivariable-adjusted
      correlations of e' (early left ventricular relaxation) and E/e' (left ventricular
      filling pressure) measured by Doppler echocardiography with 43 serum metabolites,
      quantified by magnetic resonance spectroscopy. In 2009-2013, e' cross-sectionally
      increased (Bonferroni corrected p <= 0.016) with the branched-chain amino acid
      valine (per one standard deviation increment, +0.274 cm/s (95% confidence
      interval, 0.057-0.491)) and glucose+the amino acid (AA) taurine (+0.258 cm/s
      (0.067-0.481)), while E/e' decreased ( p <= 0.017) with valine (-0.264 (-0.496- 
      0.031)). The risk of developing left ventricular diastolic dysfunction over
      follow-up (9.4%) was inversely associated ( p <= 0.0059) with baseline
      glucose+amino acid taurine (odds ratio, 0.64 (0.44-0.94). In partial least
      squares analyses of all the baseline and follow-up data, markers consistently
      associated with better diastolic left ventricular function included the amino
      acids 2-aminobutyrate and 4-hydroxybutyrate and the branched-chain amino acids
      leucine and valine, and those consistently associated with worse diastolic left
      ventricular function glucose+amino acid glutamine and fatty acid pentanoate.
      Branched-chain amino acid metabolism (-log10 p = 12.6) and aminoacyl-tRNA
      biosynthesis (9.9) were among the top metabolic pathways associated with left
      ventricular diastolic dysfunction. Conclusion The associations of left
      ventricular diastolic dysfunction with circulating amino acids and branched-chain
      amino acids were consistent over a five-year interval and suggested a key role of
      branched-chain amino acid metabolism and aminoacyl-tRNA biosynthesis in
      maintaining diastolic left ventricular function.

PMID- 30196725
TI  - Efficacy of the NICHD vaginal birth after cesarean delivery calculator: a single
      center experience.
AB  - OBJECTIVE: As the cesarean delivery rate has risen future pregnancy outcomes are
      impacted including the decision to undergo a repeat cesarean or a vaginal birth
      after cesarean (VBAC) in the subsequent pregnancy. A calculator was developed by
      the maternal fetal medicine units (MFMUs) network in 2007 to estimate the chance
      of successful VBAC and is used widely. The purpose of this study was to
      investigate the calculator's validity on our obstetric patient population. STUDY
      DESIGN: This was a retrospective study of patients attempting a VBAC delivery at
      a single center from January 2012 to June 2014. Chances for success were
      estimated using the MFMU network VBAC calculator in 201 evaluable patients. We
      then compared the calculator's results with the outcomes observed. In order to
      determine if the MFMU VBAC calculator was accurately predicting successful
      vaginal deliveries, we discretized our dataset by binning into MFMU score
      deciles. Each decile was then tested for significant deviations from the
      predicted success rate using an exact binomial test. Significance was determined
      at 0.05 levels. RESULTS: Two hundred and one patients were included. Our results
      demonstrated higher actual VBAC success than anticipated by using the MFMU
      network calculator for patients with scores in the 40-80% decile range. When
      stratified by race, we found the calculator to be a better predictor of success
      in African-American patients, as the calculator appears to underestimate success
      in white and Hispanic patients. CONCLUSION: Calculators are helpful to facilitate
      patient counseling and shared decision-making regarding the patient's choice for
      VBAC. When providing such counseling, the potential for reduced predicted VBAC
      success in the mid-decile range with the MFMU calculator should be recognized.

PMID- 30196726
TI  - Proof-of-concept preparation and characterization of dual-drug amorphous
      nanoparticle complex as fixed-dose combination of poorly soluble drugs.
AB  - OBJECTIVES: To carry out a proof-of-concept study on the development of dual-drug
      amorphous nanoparticle complex (nanoplex in short) as a potential formulation
      platform for fixed-dose combination (FDC) of poorly-soluble drugs. SIGNIFICANCE:
      FDC has been proven effective in improving patient compliance for treatment that
      requires complex multidrug regimen. Currently, there is growing interest to
      develop FDC of poorly-soluble drugs due to the increased number of drugs
      exhibiting poor solubility thus low bioavailability. METHODS: The dual-drug
      nanoplex was prepared by electrostatically-driven co-complexation of drug
      molecules with oppositely charged dextran sulfate, using ciprofloxacin (CIP) and
      itraconazole (ITZ) as the model poorly-soluble drugs. RESULTS: We first verified
      that the co-complexation products were dual-drug CIP-ITZ nanoplex, and not binary
      mixtures of the single-drug CIP and ITZ nanoplexes, by demonstrating their
      distinct thermal behaviors and dissolution characteristics. Depending on the
      preparation condition, the dual-drug nanoplex exhibited size and zeta potential
      of 160-410 nm and -35-50 mV, respectively. The individual drug payloads were
      readily manipulated by varying the CIP/ITZ mass ratio in the feed, resulting in
      CIP and ITZ payloads in the range of 60-30% and 15-45%, respectively. The CIP-ITZ
      nanoplex, however, exhibited diminished CIP supersaturation generation, thus
      lower CIP solubility enhancement, compared to the single-drug CIP nanoplex. The
      CIP-ITZ nanoplex, nonetheless, remained capable of generating high ITZ
      supersaturation level. CONCLUSION: Dual-drug nanoplex was successfully prepared
      with a high degree of control over its physical characteristics. Nevertheless,
      whether dual-drug nanoplex always exhibits diminished solubility enhancement
      compared to its single-drug counterparts needs to be investigated using different
      poorly-soluble drugs.

PMID- 30196727
TI  - Targeted agents for HER2-positive breast cancer in older adults: current and
      future perspectives.
AB  - INTRODUCTION: One-third of breast cancer (BC) cases worldwide occur in women aged
      65 years and older, with 10 to 15% overexpressing the human epidermal growth
      factor receptor 2 (HER2). Although several HER2-targeted therapies have been
      developed, the lack of data regarding their use in older patients hampers
      evidence-based decision-making for this population. Areas Covered: We review
      current evidence on the efficacy and safety of HER2-targeted therapies in older
      adults with BC, focusing on approved therapies such as trastuzumab, lapatinib,
      pertuzumab, ado-trastuzumab-emtansine, and neratinib. Additionally, we discuss
      drugs under development to target the HER2-receptor, and to overcome resistance
      to existing therapies. Finally, we highlight the cardiotoxicity of HER2-targeted
      drugs among older adults. Expert Opinion: Older adults are underrepresented in
      trials of HER2-targeted therapies in BC. We propose strategies to increase
      recruitment of older adults in clinical trials in order to increase the evidence
      base to treat this growing population.

PMID- 30196728
TI  - Investigation of Heme Oxygenase 2 Enzyme Protein Expression in Keratoconus and
      Normal Human Corneal Epithelium: An Immunohistochemical Study.
AB  - PURPOSE: To compare heme oxygenase 2 (HO-2) enzyme levels detected by
      immunohistochemical staining methods in the cornea epithelium obtained from
      keratoconus patients and normal subjects. MATERIALS AND METHODS: The keratoconus
      group included 69 eyes of 69 patients with keratoconus scheduled for cross
      linking surgery. The control group included 52 eyes of 52 patients with
      refractive error scheduled for photorefractive keratectomy surgery. After a
      detailed ophthalmologic examination, corneal topographic maps of each patient
      were generated, and then the patients underwent surgery. The corneal epithelium
      was collected mechanically during the surgery, fixed with formalin, embedded in
      paraffin blocks, and sectioned by microtomes. HO-2 antibodies were applied to the
      samples for immunohistochemical evaluation. The intensity of the staining was
      identified as negative, weak, moderate or strong. The keratoconus group was
      classified as early (average keratometry (AvrK) <= 47 D), moderate (AvrK 47-55 D)
      and advanced keratoconus (AvrK >= 55 D). Finally, intergroup and intragroup
      comparison analyses were made statistically. RESULTS: In the keratoconus group,
      20 (29%) (14 weak and 6 moderate staining) of the 69 corneal epithelial specimens
      were identified with HO-2 expression. In the control group, 40 (76.9%) (16
      moderate and 24 strong staining) of the 52 corneal epithelial specimens were
      identified with HO-2 expression. HO-2 expression in the corneal epithelial
      specimens was significantly less in the keratoconus group than in the control
      group (p < 0.001). There was no substantial difference among the keratoconus
      subgroups in terms of staining with the HO-2 antibody (p = 0.797). CONCLUSIONS:
      The HO-2 enzyme staining using immunohistochemical methods was at lower amounts
      in the keratoconic corneal epithelial cells as compared with normal corneal
      epithelial cells. The HO-2 enzyme may play a role in the etiopathogenesis of
      keratoconus.

PMID- 30196729
TI  - Drugs that increase the risk of community-acquired pneumonia: a narrative review.
AB  - INTRODUCTION: Community-acquired pneumonia (CAP), a major cause of morbidity and
      mortality, is the leading infectious cause of death in the developed world.
      Population-based studies and systematic reviews have identified a large number of
      risk factors for the development of pneumonia in adults. In addition to age,
      lifestyle habits, and comorbidities, some forms of pharmacotherapy may also
      increase the risk for CAP. Areas covered: MEDLINE, CENTRAL, and Web of Science
      were used in 2017 to search for case-control, cohort studies, as well as
      randomized controlled trials and meta-analysis that involved outpatient proton
      pump inhibitors (PPIs), inhaled corticosteroids (ICSs), antipsychotics, oral
      antidiabetics, and CAP diagnosis in patients aged >18 years. Expert opinion: Our
      review confirmed that the use of ICSs, PPIs or antipsychotic drugs was
      independently associated with an increased risk for CAP. We also identified a
      positive association between specific oral antidiabetics and the development of
      pneumonia.

PMID- 30196730
TI  - Exclusive breast feeding and dehydration fever in newborns during the first days
      of life.
AB  - OBJECTIVES: To determine the prevalence of dehydration fever in infants admitted
      to the Neonatal Intensive Care Unit (NICU) from the well newborn nursery with
      fever in the first days of life. STUDY DESIGN: Retrospective data analysis of
      term infants admitted to the NICU from the well newborn nursery with fever (n =
      75). Infants were divided into two groups based on hydration status using
      clinical and laboratory signs of dehydration. Clinical and laboratory variables
      were compared between the two groups. RESULTS: Fifty-three of the 75 infants
      admitted to the NICU with fever had clinical and laboratory signs of dehydration
      (71%). Infants with dehydration were more likely to be exclusively breast fed and
      present with fever at >24 h of age. There were no positive blood or cerebrospinal
      fluid cultures in infants with dehydration. The incidence of dehydration fever
      increased after implementation of an "Exclusive Breast Feeding" policy from
      1.4/1000 to 3.5/1000 live births (p <= .01). CONCLUSIONS: Dehydration is
      associated with fever in exclusively breast fed infants during the first several
      days of life. There were no cases of serious bacterial or viral infections in the
      cohort of febrile infants with clinical and laboratory signs of dehydration.

PMID- 30196731
TI  - Challenges in the management of asthma associated with smoking-induced airway
      diseases.
AB  - INTRODUCTION: Smoking-induced airway diseases such as chronic bronchitis,
      emphysema, and small airway dysfunction contribute to the chronic respiratory
      symptoms experienced by adults with asthma, including those with spirometric
      chronic obstructive pulmonary disease (COPD), termed asthma-COPD overlap (ACO).
      Drug treatment of symptomatic smokers with asthma or ACO is uncertain due to
      their exclusion from most clinical trials. Areas covered: This review summarizes
      evidence for the efficacy of small molecule drugs used in the clinic to treat
      current and former smokers with a diagnostic label of asthma or ACO. Other
      therapeutic interventions are reviewed, including smoking cessation and
      biologics. Expert opinion: Clinical trials and observational studies suggest that
      smoking cessation and approved drugs used to treat non-smokers with asthma
      produce clinical benefits in smokers with asthma or ACO, although the overall
      quality of evidence is low. The efficacy of some treatments for asthma is altered
      in current smokers, including reduced responsiveness to short-term inhaled
      corticosteroids and possibly improved responsiveness to leukotriene receptor
      antagonists. Preliminary findings suggest that low-dose theophylline, statins,
      and biologics, such as omalizumab, mepolizumab, and dupilumab, may improve
      clinical outcomes in smokers with asthma or ACO. Improved phenotyping and
      endotyping of asthma and smoking-induced airway diseases should lead to better
      targeted therapies.

PMID- 30196732
TI  - Low molecular weight chitosan-based conjugates for efficient Rhein oral delivery:
      synthesis, characterization, and pharmacokinetics.
AB  - OBJECTIVE: This article aims to design low molecular weight chitosan (LMWC)-based
      conjugates of Rhein (RH) by means of an amino acid linker (Alanine) for improved
      solubility and enhanced bioavailability. SIGNIFICANCE: Rhein is a potential
      candidate for the therapy of kidney disease. However, the poor solubility,
      inadequate bioavailability, and lack of proper formulation restrict its clinical
      applicability. LMWC-drug conjugates offer the potential to improve the water
      solubility of RH, increase its oral absorption, and thereby enhance its
      bioavailability. METHODS: The conjugates were synthesized via a carbodiimide
      reaction and confirmed using UV-vis, FTIR, and 1H-NMR spectroscopy. The water
      solubility and in vitro release properties were evaluated. Free RH and RH-LMWC
      conjugates were administered at an equivalent oral gavage dose of RH at 35 mg/kg
      for pharmacokinetic studies in Sprague Dawley rats. RESULTS: The conjugates with
      RH content of 9.65% were successfully synthesized and featured a satisfactory
      water-solubility of 9.73 mg/mL, which exhibited a sustained release pattern over
      72 h, and the enzymes present may promote the degradation of the conjugate to
      increase the release of Rhein. Oral administration of RH-LMWC conjugates to rats
      led to seven-folds and 3.1-folds increase in the T1/2 and AUC0-infinity,
      respectively, as compared to RH suspension. CONCLUSION: The present work
      demonstrated that the RH-LMWC conjugates exhibited sustained release properties
      with outstanding oral bioavailability enhancements compared to administration of
      RH itself. Potentially, RH-LMWC conjugates may serve as a promising lead for
      developing a new platform for RH oral delivery.

PMID- 30196733
TI  - The association between selected mid-trimester amniotic fluid candidate proteins
      and spontaneous preterm delivery.
AB  - OBJECTIVE: The aim of this study was to explore inflammatory response and
      identify early potential biomarkers in mid-trimester amniotic fluid associated
      with subsequent spontaneous preterm delivery (PTD). METHODS: A cohort study was
      performed at Sahlgrenska University Hospital/Ostra, Gothenburg, Sweden, between
      2008 and 2010. Amniotic fluid was collected from consecutive women undergoing mid
      trimester transabdominal genetic amniocentesis at 14-19 gestational weeks.
      Clinical data and delivery outcome variables were obtained from medical records.
      The analysis included 19 women with spontaneous PTD and 118 women who delivered
      at term. A panel of 26 candidate proteins was analyzed using Luminex xMAP
      technology. Candidate protein concentrations were analyzed with ANCOVA and
      adjusted for plate effects. RESULTS: The median gestational age at delivery was
      35 + 3 weeks in women with spontaneous PTD and 40 + 0 weeks in women who
      delivered at term. Nominally significantly lower amniotic fluid levels of
      adiponectin (PTD: median 130,695 pg/mL (IQR 71,852-199,414) vs term: median
      185,329 pg/mL (IQR (135,815-290,532)), granulocyte-macrophage colony stimulating
      factor (PTD: median 137 pg/mL (IQR 74-156) vs term: median 176 pg/mL (IQR 111
      262)), and macrophage migration inhibitory factor (PTD: median 3025 pg/mL (IQR
      1885-3891) vs term: median 3400 pg/mL (IQR 2181-5231)) were observed in the
      spontaneous PTD group, compared with the term delivery group, after adjusting for
      plate effects. No significant differences remained after Bonferroni correction
      for multiple comparisons. CONCLUSIONS: Our results are important in the process
      of determining the etiology behind spontaneous PTD but due to the non
      significance after Bonferroni correction, the results should be interpreted with
      caution. Further analyses of larger sample size will be required to determine
      whether these results are cogent and to examine whether microbial invasion of the
      amniotic cavity or intra-amniotic inflammation occurs in asymptomatic women in
      the mid-trimester with subsequent spontaneous PTD.

PMID- 30196734
TI  - The role of fetal growth restriction in the association between Down syndrome and
      perinatal mortality.
AB  - OBJECTIVE: Down syndrome (DS) is associated with significant risk of perinatal
      mortality. We hypothesize that this association is primarily mediated through the
      effects of fetal growth restriction (FGR). METHODS: This was a retrospective
      cohort analysis using the US Natality Database from 2011 to 2013. Analysis was
      limited to singleton nonanomalous pregnancies or confirmed DS pregnancies without
      severe structural anomalies between 24 and 42 w in gestation. The risk of
      stillbirth (SB) associated with DS was estimated using both Cox proportional
      Hazard (HR) regression and accelerated failure time (AFT) methods. The risk of
      neonatal mortality was estimated using logistic regression analyses. Mediation
      analysis was then performed to estimate the effect of small for gestational age
      (SGA), defined as birthweight <=10th percentile for gestational age, on perinatal
      mortality associated with DS. All regression models were selected using backward
      stepwise elimination method. The final regression models included adjustment for
      maternal age, hypertension, and diabetes. RESULTS: The final cohort included 2446
      DS cases among 9,804,718 births. The overall SB rate was 223.6/1000 births in DS
      group and 4.7/1000 births without DS (p < .001, adjusted hazard ratio (aHR):
      58.25; 95% CI [53.44,63.49]). Based on the AFT model, DS survival-to-delivery
      rate is 4.3 times lower (TR: 0.23; 95% CI [0.22,0.24]). Thirty-five percentage of
      the effect of DS on stillbirth was mediated through SGA (% mediation:35.1%; 95%
      CI [33.7,36.4]). The rate of neonatal mortality among DS was 69.0/1000 births
      compared with 2.8/1000 births without DS (p < .001, adjusted odds ratio (aOR):
      27.16; 95% CI: [22.63,32.60]). Only 11.6% of the effect of DS on neonatal deaths
      was mediated through SGA (%mediation:11.6%; 95% CI [8.4,10.6]). CONCLUSION: Over
      one-third of overall stillbirths were mediated through SGA. Routine surveillance
      of fetal growth and standard SGA surveillance protocols may reduce the risk of
      perinatal mortality in DS pregnancies. Conversely, it is important to point out
      that these surveillance strategies may not be effective two-third of the cases
      not affected by growth restriction.

PMID- 30196735
TI  - Mobility following cesarean delivery: an observational study utilizing
      pedometers.
AB  - INTRODUCTION: Thromboembolic events are a leading cause of maternal death, and
      peak in the postpartum period. We aimed to assess immediate patient mobility
      following cesarean delivery (CD) with digital step counters (pedometers), and to
      characterize factors associated with reduced mobility. MATERIALS AND METHODS:
      This was a prospective observational study at the maternity unit of the Edith
      Wolfson Medical Center between June 2017 and February 2018. Patients who
      underwent a cesarean - primary and repeat, and emergent and nonemergent - were
      asked to wear pedometers for 48 h following cesarean. Comparison of maternal
      characteristics, surgical, and postpartum course was performed between three
      groups: high mobility patients (n = 33), intermediate mobility patients (n = 34),
      and low mobility patients (n = 34), according to the upper third of steps
      recorded, intermediate third, and the lower third, respectively. RESULTS: The
      average number of steps taken during the first 48 h following delivery was 6974
      +/- 2582, 2724 +/- 732, and 1056 +/- 454 in the high, intermediate, and low
      mobility groups, respectively, p < .001. Patients' demographics, parity,
      intrapartum, and postpartum course were not found to be associated with patient
      mobility. However, smokers were found to walk an additional 1549 steps following
      CD as compared to nonsmokers. CONCLUSION: This study failed to identify risk
      factors for reduced mobility in the immediate postpartum period, but an increased
      mobility was noted in smokers, most probably related to the need to ambulate
      outside the maternity ward. The decision to treat patients following a cesarean
      with thromboprophlaxis will continue to be based on previously identified risk
      factors.

PMID- 30196737
TI  - Comparing the Accuracy of Mass Casualty Triage Systems in a Pediatric Population.
AB  - INTRODUCTION: It was previously difficult to compare the accuracy of different
      mass casualty triage systems to one another. This pilot study is one of the first
      attempts to operationalize an expert panel's criterion standard definitions of
      triage categories in a pediatric population in order to compare accuracy between
      different systems. OBJECTIVE: To compare the accuracy of 4 different mass
      casualty triage systems (SALT, JumpSTART, Triage Sieve, and CareFlight) when used
      for children. METHODS: We observed the emergency department triage of patients
      less than 18 years old presenting to the only pediatric specialty hospital/Level
      1 trauma center in Milwaukee County, Wisconsin. A single, certified EMS provider
      observed each patient's initial triage in the emergency department and recorded
      all findings that were necessary to categorize the patient using each of the 4
      mass casualty triage systems being studied. Hospital medical records were then
      reviewed for each patient and assigned a criterion standard triage category based
      on the treatments received and final disposition. Descriptive statistics were
      used to compare accuracy, over-, and under-triage rates for each of the triage
      systems. RESULTS: A total of 115 subjects were enrolled. Of those, 51% were male
      and 57% were transported by ambulance. When compared to the criterion standard
      definitions, SALT was found to have the highest accuracy rate (59%; 95% CI 50-68)
      compared to JumpSTART (57%; 95% CI 48-66), CareFlight (56%; 95% CI 47-65), and
      TriageSieve (56%; 95% CI 46-65). SALT also had the lowest under-triage rate (33%;
      95% CI 24-42) compared to JumpSTART (39%; 95% CI 30-48), CareFlight (39%; 95% CI
      30-48), and TriageSieve (39%; 95% CI 30-48). SALT had the highest over-triage
      rate (6%; 95% CI 2-11) compared to JumpSTART (4%; 95% CI 1-8), CareFlight (5%;
      95% CI 1-9), and TriageSieve (5%; 95% CI 1-9). However, the confidence intervals
      for both the accuracy and under-triage rates overlapped between all triage
      systems. For each triage system, the most common error was designating a patient
      as "minimal" that, according to the criterion standard, should have been triaged
      as "delayed." CONCLUSION: We found that the 4 most popular mass casualty triage
      systems preformed similarly in an emergency department-based pediatric
      population. None of the systems were extremely accurate, and each demonstrated an
      unacceptable amount of under-triage. Better differentiating between patients
      categorized as "minimal" and "delayed" may improve the accuracy of mass casualty
      triage systems.

PMID- 30196738
TI  - Consequences of unintended pregnancy on mother and fetus and newborn in North
      East of Iran.
AB  - INTRODUCTION: Unintended pregnancy is one of the most important public health
      problems. The complications of unintended pregnancy can lead to mortality and
      irreversible health damages in the whole world and may involve the mother, fetus,
      and neonate. This study aims to determine the most important complications of
      unintended pregnancy for mother, her fetus, and neonate. MATERIALS AND METHODS:
      This retrospective cohort study was conducted to assess the effects of unintended
      pregnancy on pregnant women in Bojnourd County, North Khorasan Province, Iran. In
      total 748 pregnant mothers were selected, including 374 mothers as exposed group
      (unintended pregnancy) and 374 as unexposed group (planned pregnancy). The data
      were collected using a researcher-made checklist and the mothers were interviewed
      by phone to complete the data. RESULTS: The relationship between unintended
      pregnancy with maternal complications of maternal age (R2adj = 1.03) (p = .044),
      education level (R2adj = 2.01) (p < .001), mother's job (R2adj = 0.88) (p =
      .025), father's job (R2adj = 0.86) (p = .018), number of prenatal cares (R2adj =
      0.80) (p < .001), private specialist visit (R2adj = 0.28) (p = .001), use of
      certain drugs (R2adj = 2.58) (p = .001), gestational weight gain (R2adj = 1.79)
      (p = .01), vaginal bleeding (R2adj = 3.81) (p = .004), breastfeeding start 3-h
      postpartum (R2adj =19.06) (p < .001), gestational diabetes (R2adj = 12.94) (p <
      .001), and urinary tract infection (R2adj = 7.48) (p < .001) was significant
      after adjusting for confounding factors in the logistic regression model. There
      was a significant relationship between unintended pregnancy with neonatal
      variables such as deviation of 6- to 12-month neonate from height growth (R2adj =
      4.78) (p = .016) and from weight growth (R2adj = 2.01) (p = .011), as well as the
      presence of another infant under 2 years in the family (R2adj = 4.28) (p = .014).
      CONCLUSION: It is concluded that unwanted pregnancy seems to have substantial
      negative consequences for women during their pregnancy and also her children. It
      is suggested health policy makes in Iran consider this important issue in
      national reproductive health and family program to reduce healthcare burden.

PMID- 30196739
TI  - Association between time from cessation of oxytocin infusion for labor to
      delivery and intraoperative severe blood loss during cesarean section: a
      retrospective cohort study.
AB  - AIM: Prolonged oxytocin infusion during labor results in receptor desensitization
      and increases the risk of obstetric hemorrhage. We aimed to examine the
      association between recovery time (RT) and intraoperative severe blood loss in
      women who underwent a cesarean section after oxytocin pretreatment. METHODS: We
      retrospectively assessed 103 Japanese women who underwent cesarean section after
      oxytocin pretreatment. RT (time from cessation of oxytocin infusion during labor
      to delivery) and intraoperative severe blood loss (active bleeding exceeding 1000
      mL) were measured. Confounding factors were controlled, and RT cut-off value
      associated with severe blood loss and association between RT and intraoperative
      severe blood loss were assessed. RESULTS: The mean maternal age was 34 years, and
      100 (97.1%) women delivered at term. Mean RT was 121.6 min. The overall incidence
      of intraoperative severe blood loss was 22.3% (23/103). The cut-off point to
      predict intraoperative severe blood loss was 96 min (sensitivity, 65.2%;
      specificity, 81.3%). On multivariate analysis, an RT of <=96 min [adjusted odds
      ratio (OR), 11.9; 95% confidence interval (CI), 3.32-42.7] and macrosomia
      (adjusted OR, 3.91; 95% CI, 1.10-13.8) were associated with intraoperative severe
      blood loss. CONCLUSIONS: Consideration of RT is helpful in the management of
      women undergoing cesarean section after oxytocin pretreatment.

PMID- 30196736
TI  - DNA damage-induced dynamic changes in abundance and cytosol-nuclear translocation
      of proteins involved in translational processes, metabolism, and autophagy.
AB  - Ionizing radiation (IR) causes DNA double-strand breaks (DSBs) and activates a
      versatile cellular response regulating DNA repair, cell-cycle progression,
      transcription, DNA replication and other processes. In recent years proteomics
      has emerged as a powerful tool deepening our understanding of this multifaceted
      response. In this study we use SILAC-based proteomics to specifically investigate
      dynamic changes in cytoplasmic protein abundance after ionizing radiation; we
      present in-depth bioinformatics analysis and show that levels of proteins
      involved in autophagy (cathepsins and other lysosomal proteins), proteasomal
      degradation (Ubiquitin-related proteins), energy metabolism (mitochondrial
      proteins) and particularly translation (ribosomal proteins and translation
      factors) are regulated after cellular exposure to ionizing radiation.
      Downregulation of no less than 68 ribosomal proteins shows rapid changes in the
      translation pattern after IR. Additionally, we provide evidence of compartmental
      cytosol-nuclear translocation of numerous DNA damage related proteins using
      protein correlation profiling. In conclusion, these results highlight unexpected
      cytoplasmic processes actively orchestrated after genotoxic insults and protein
      translocation from the cytoplasm to the nucleus as a fundamental regulatory
      mechanism employed to aid cell survival and preservation of genome integrity.

PMID- 30196740
TI  - Is the risk of small for gestational age influenced by maternal body composition
      in young Japanese women?
AB  - BACKGROUND: We aimed to investigate whether there was a high incidence of young
      Japanese mothers being underweight (pregravid body mass index [BMI] < 18.5 kg/m2)
      and if they delivered infants who were small for gestational age (SGA). MATERIALS
      AND METHODS: Our study was carried out from 2013 to 2017 and included adolescent
      women (maternal age at delivery: <20 years old; n = 94), women in their early
      twenties (maternal age at delivery: 20-24 years; n = 479), and controls (maternal
      age at delivery: 25-34 years; n = 2061). RESULTS: In both the adolescent and
      early twenties groups, the incidence of being underweight, based on prepregnancy
      BMI, was significantly higher than controls (p < .0001 and p < .05,
      respectively). In both groups, gestational weight gain (GWG) was significantly
      higher than controls (p < .0001). There were no notable group differences in the
      incidences of SGA. CONCLUSION: The incidence of being underweight was higher in
      younger mothers than in controls. However, the risk of SGA did not increase in
      younger mothers, possibly because their GWG overcame the influence of their pre
      pregnancy body composition.

PMID- 30196741
TI  - Outcome after fetoscopic laser coagulation in twin-twin transfusion syndrome - is
      the survival rate of at least one child at 6 months of age dependent on
      preoperative cervical length and preterm prelabour rupture of fetal membranes?
AB  - PURPOSE: Twin-to-twin transfusion syndrome (TTTS) complicates 10-15% of all
      monochorionic twin pregnancies. Selective laser coagulation of placental
      anastomoses is the only causal therapy. The aim of this study was to analyze the
      neonatal survival, the survival rate of at least one child at 6 months of age,
      and maternal outcome after laser therapy in a Swiss cohort. MATERIAL AND METHODS:
      Between 2008 and 2014, 39 women were treated with fetoscopic laser procedure due
      to TTTS. Two women were excluded from the study because of missing informed
      consent or loss of follow-up. The women were divided into two groups: group 1
      with a cervical length >25 mm and group 2 with a cervical length <=25 mm. The
      primary end point was the survival rate of at least one child at 6 months of age
      and its dependence on maternal preoperative cervical length or the time interval
      between operation (OP)-preterm prelabour rupture of fetal membranes (PPROM).
      Secondary outcomes were neonatal complications and maternal complications due to
      the procedure. Statistical analysis was performed using the program SPSS 22. A p
      value of <.05 was considered statistically significant. RESULTS: Mean gestational
      age (GA) at OP of group 1 (20.3 +/- 3 GW) was comparable with group 2 (21.5 +/-
      2.4 GW; p = .27). The GA at birth was significantly higher in group 1 (31.5 +/-
      5.9 GW) than in group 2 (27.0 +/- 4.7 GW: p = .02). The survival rate of at least
      one child at 30 days and 6 months of age was 81% in group 1 and only 60% in group
      2 (p = .1). PPROM <32 GW occurred in 43%. The survival rate of at least one child
      was significantly higher if the OP-PPROM interval was >28 days (93 versus 43%; p
      = .02). Major brain injury was observed in 11% of infants. Severe maternal
      complications (pulmonary edema) occurred in three cases (8%). CONCLUSIONS: Our
      survival rate of at least one child at 30 days and 6 months of age and the
      outcome of the mothers is well comparable to other international studies. A
      preoperative maternal cervical length of >25 mm and an occurrence of PPROM more
      than 28 days after the laser therapy is associated with a higher survival rate of
      at least one child at 6 months of age.

PMID- 30196742
TI  - Evidence for intra-mitochondrial variation in population genetic structure of
      Platycephalus sp.1 In the Northwestern Pacific.
AB  - Understanding evolutionary dynamics of population structure and genetic diversity
      of marine fish species is of great importance for fishery management and resource
      conservation. Platycephalus sp.1 is a commercially important marine fish in the
      Northwestern Pacific. Yet, current understanding of population genetic patterns
      of Platycephalus sp.1 remains limited. In this study, the Platycephalus sp.1
      individuals from four populations in the Northwestern Pacific, which cover large
      geographic distances and latitudinal gradients, were sampled to examine genetic
      diversity and population structure by investigating the mitochondrial sequences
      of Cytochrome b (CYTB, 1141 bp) and control region (CR, 458 bp), and then to
      assess intra-mitochondrial genetic variability by using a combination of
      population- and individual-based analytical approaches. Moderate to low levels of
      genetic diversity were observed in sampled populations by investigating both CR
      and CYTB datasets. In CR dataset, weak genetic differentiation among populations
      were observed and population Tokyo Bay was significantly differentiated with
      other sampled populations. In CYTB dataset, lower genetic differentiations were
      observed and population Beihai (BH) was significantly differentiated. A non
      synonymous substitution was predominantly detected in population BH, and such
      substitution was tested as a significantly positive selective site in natural
      selection tests. Based on these findings, we propose that local adaptation
      influenced by natural selection contributes largely to the intra-mitochondrial
      variation in Platycephalus sp.1 populations. The present study provides new
      perspectives on the population genetic structure of Platycephalus sp.1, which
      could have important implications for the sound management and conservation of
      this fishery species.

PMID- 30196743
TI  - Correlation of single nucleotide polymorphisms in the promoter region of the
      ANXA5 (annexin A5) gene with recurrent miscarriages in women of Greek origin.
AB  - BACKGROUND: Recent findings show that a number of single nucleotide polymorphisms
      (SNPs) within the promoter region of the annexin A5-gene (ANXA5) reduce the
      expression of the reporter gene and so they display a significant association
      with recurrent pregnancy loss (RPL). OBJECTIVE: The objective of the present
      study aimed to address the contribution of ANXA5 M2 haplotype consisting of four
      minor alleles: (SNP1: (-)467G > A, SNP2: (-)448A > C, SNP3: (-)422T > C, and
      SNP4: (-)373G > A) in the occurrence of recurrent pregnancy losses in the Greek
      population, and the role of further two minor alleles: SNP5: (-)302 T > G and
      SNP6: (-)1C > T as independent risk factors for RPL. METHODS: A 752-bp genomic
      region of ANXA5 promoter was amplified by PCR using specific primers. Genotypic
      analysis by Sanger sequencing was performed for these six SNPs (minor alleles) in
      the promoter region of ANXA5 gene, in 100 (100) Greek women with recurrent
      miscarriages (median =3) and 70 (70) fertile controls. Statistical analysis was
      done using the SAS 9.3 for Windows (SAS Institute Inc, NC, USA) and SPSS packages
      for Windows (C.DiMaggio 2013, SAS Institute 2014). RESULTS: This case-control
      study revealed that there is no significantly increased risk of RPL among the
      M2/ANXA5 haplotype carriers in the Greek population, as there were no statistical
      differences between the patients with recurrent pregnancy losses and the fertile
      controls (11.5% in RPL cases versus 9.29% in controls, p-value: .6364). There was
      no difference in SNP5 and SNP6 minor carriership between the two groups. In
      particular, carriers of SNP5 and SNP6 had an increased risk for RPL state with
      odds ratio: 1.2472 and 1.3846 respectively, however without statistically
      significant importance. CONCLUSION: The M2/ANXA5 haplotype does not differ
      between RPL patients and controls in the Greek population. Also, it is the first
      time that SNP5 and SNP6 minor alleles were evaluated extensively in women of
      European origin with recurrent pregnancy losses (RPL), and they do not seem to be
      independent risk factors in the occurrence of RPL in the Greek population.
      Though, this has to be confirmed in further and larger clinical trials with women
      of European origin.

PMID- 30196744
TI  - ATG5 is required for B cell polarization and presentation of particulate
      antigens.
AB  - : The involvement of macroautophagy/autophagy proteins in B-cell receptor (BCR)
      trafficking, although suspected, is not well understood. We show that ATG5
      (autophagy related 5) contributes to BCR polarization after stimulation and
      internalization into LAMP1 (lysosomal-associated membrane protein 1)+ and major
      histocompatibility complex class II (MHC-II)+ compartments. BCR polarization is
      crucial in the context of immobilized antigen processing. Moreover, antigen
      presentation to cognate T cells is decreased in the absence of ATG5 when the
      model antigen OVAL/ovalbumin is provided in an immobilized form in contrast to
      the normal presentation of soluble OVAL. We further show that ATG5 is required
      for centrosome polarization and actin nucleation in the immune synapse area. This
      event is accompanied by an increased interaction between ATG16L1 (autophagy
      related 16-like 1 [S. cerevisiae]) and the microtubule-organizing center
      associated protein PCM1 (pericentriolar material 1). In the human B cell line
      BJAB, PCM1 is required for BCR polarization after stimulation. We thus propose
      that the ATG12 (autophagy related 12)-ATG5-ATG16L1 complex under BCR stimulation
      allows its interaction with PCM1 and consequently facilitates centrosome
      relocalization to the immune synapse, optimizing the presentation of particulate
      antigens. ABBREVIATIONS: ACTB: actin beta; ACTR2/3: ARP2/3 actin-related protein
      2/3; APC: antigen-presenting cells; ATG: autophagy-related; BCR: B cell receptor;
      BECN1/Beclin 1: beclin 1, autophagy related; CDC42: cell division cycle 42; Cr2:
      complement receptor 2; CSFE: carboxyfluorescein succinimidyl ester; DAPI: 4',6
      diamidino-2-phenylindole dihydrochloride; EEA1: early endosome antigen 1; ELISA:
      enzyme-linked immunosorbent assay; FITC: fluorescein isothyocyanate; GC: germinal
      center; GJA1/CX3: gap junction protein, alpha 1; Ig: immunoglobulin; LAMP1:
      lysosomal-associated membrane protein 1; LAP: LC3-associated phagocytosis; LM:
      littermate; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3;
      MAPK/ERK: mitogen activated protein kinase; MHC-II: major histocompatibility
      complex class II; MIIC: MHC class II compartment; OVAL: ovalbumin; PBS: phosphate
      buffered saline; PCM1: pericentriolar material 1; PtdIns3K: phosphatidylinositol
      3-kinase; PTPRC/CD45RB/B220; Protein tyrosine phosphatase, receptor type, C; SYK:
      spleen tyrosine kinase; TBS: Tris-buffered saline; TCR: T cell receptor; ULK1:
      unc-51 like kinase 1.

PMID- 30196745
TI  - Screening Strategies and Methods for Better Off-Target Liability Prediction and
      Identification of Small-Molecule Pharmaceuticals.
AB  - Pharmaceutical discovery and development is a long and expensive process that,
      unfortunately, still results in a low success rate, with drug safety continuing
      to be a major impedance. Improved safety screening strategies and methods are
      needed to more effectively fill this critical gap. Recent advances in informatics
      are now making it possible to manage bigger data sets and integrate multiple
      sources of screening data in a manner that can potentially improve the selection
      of higher-quality drug candidates. Integrated screening paradigms have become the
      norm in Pharma, both in discovery screening and in the identification of off
      target toxicity mechanisms during later-stage development. Furthermore, advances
      in computational methods are making in silico screens more relevant and suggest
      that they may represent a feasible option for augmenting the current screening
      paradigm. This paper outlines several fundamental methods of the current drug
      screening processes across Pharma and emerging techniques/technologies that
      promise to improve molecule selection. In addition, the authors discuss
      integrated screening strategies and provide examples of advanced screening
      paradigms.

PMID- 30196746
TI  - High prevalence of vitamin D insufficiency in professional handball athletes.
AB  - OBJECTIVES: Vitamin D affects multiple body functions through the regulation of
      gene expression. In sports medicine, its influence on musculoskeletal health and
      performance is of particular interest. Vitamin D insufficiency might decrease
      athletic performance and increase the risk of musculoskeletal injuries. Several
      studies have demonstrated vitamin D deficiency in professional athletes; however,
      the prevalence of vitamin D insufficiency in professional handball players is yet
      unknown. METHODS: The study was planned as a prospective, non-interventional
      study. We examined 70 male elite handball athletes (first league) in a pre
      competition medical assessment in July. Age, height, weight, body mass index, 25
      OH vitamin D, calcium, and parathyroid hormone were evaluated, and a sun exposure
      score was calculated. Players were then divided into two groups of vitamin D
      levels: insufficient (<30 ng/mL) and sufficient (>=30 ng/mL). RESULTS: The mean
      25-OH vitamin D level of the 70 players was 33.5 +/- 10.9 ng/mL (median 32.2, IQR
      26.5-38.9 ng/mL). Thirty-nine (55.7%) had sufficient and 31 (44.3%) insufficient
      levels. Athletes with sufficient vitamin D levels had significantly lower
      parathyroid hormone levels than athletes with insufficiency (24.9 +/- 12.1 vs.
      33.5 +/- 15.1 ng/mL, p = 0.02). All other parameters evaluated demonstrated no
      significant difference between the two groups. CONCLUSION: Vitamin D
      insufficiency is a common finding in professional handball athletes even in
      summer, which might negatively affect physical performance. Furthermore, it might
      lead to an increased risk of musculoskeletal injuries and infections. This should
      be evaluated in further studies.

PMID- 30196747
TI  - Toxoplasma gondii profilin does not stimulate an innate immune response through
      bovine or human TLR5.
AB  - Toxoplasma gondii is responsible for one of the most prevalent infections in
      people. T. gondii profilin (TgPr) is a protein integral to parasite movement and
      cellular invasion. Murine TLRs has been described to bind TgPr. Furthermore, more
      recently, human TLR5 has been described to recognise recombinant TgPr, as well as
      bacterial flagellin. In addition to infections in humans, T. gondii infects farm
      animals, but little information is available about its innate recognition. We
      aimed to investigate whether, similarly to their human orthologue, bovine and
      porcine TLR5 could also be stimulated by TgPr by using a combination of reporter
      cell lines expressing full length TLR5 from each species as well as primary
      cells. Although human and bovine TLR5-transfected cells responded to flagellin,
      no response was detected upon stimulation with profilin. Furthermore, TgPr failed
      to elicit IL-6 secretion in human peripheral blood mononuclear cells and CD14+
      monocytes. In contrast, exposure of RAW cells, known to express TLR11, to TgPr
      slightly increased the IL-6 response. Our data cast doubts on the possibility
      that profilin is a specific ligand for human TLR5 and bovine TLR5. This leaves
      the immunogenic properties of this potential target antigen (Ag) uncharacterised
      outside of the murine system.

PMID- 30196748
TI  - Skull pathology in 10 cats with patellar fracture and dental anomaly syndrome.
AB  - Case series summary The aim of this case series is to describe the clinical and
      radiological features of mandibular and maxillary abnormalities in cats diagnosed
      with patellar fractures and dental anomalies, a condition that we have named
      'patellar fracture and dental anomaly syndrome' (PADS), also known previously as
      'knees and teeth syndrome'. Where available, clinical records, skull and/or
      intraoral dental radiographs, head CT images, microbiology and histopathology
      reports were collected, and follow-up was obtained. Ten cats with mandibular or
      maxillary abnormalities were identified. Common clinical features included
      multiple persistent deciduous teeth, gingivitis and swellings of the jaw. Skull
      radiographs were available for 7/10 cats and head CT images were available for
      one cat. Findings included marked bony and periosteal proliferation, hypodontia,
      root resorption, root malformation and unerupted permanent teeth. Where
      available, microbiology and histopathology results were consistent with
      osteomyelitis. Relevance and novel information Mandibular and maxillary
      abnormalities are an additional unreported clinical feature of the rare condition
      that we have termed PADS. Radiologically, these lesions can have an aggressive
      appearance, which can mimic neoplasia. Medical management with antibiotic and
      anti-inflammatory therapy improves clinical signs in the short term; however,
      surgical extraction of persistent deciduous and unerupted permanent teeth, and
      debridement of proliferative and necrotic bone appear to be necessary for an
      improved outcome. Additional information on long-term outcome is required.

PMID- 30196750
TI  - Broadcasting War Trauma: An Exploratory Netnography of Veterans' YouTube Vlogs.
AB  - This exploratory netnographic study is among the first to investigate military
      video blogs (milvlogs) posted by Iraq and Afghanistan veterans who self-published
      stories on military-related trauma to YouTube. Studies have shown that self
      published milvlogs provide benefits such as education, social support, and self
      management of chronic physical and psychological illness. The aim of this study
      was to explore combat veterans' milvlogs and to determine themes that emerged
      across the videos. We transcribed and analyzed content from 17 milvlogs. Our
      analysis yielded seven themes: motivation, loss, managing symptoms, help-seeking,
      guilt and shame, suicide, and connecting to other veterans. We concluded that
      veterans were initially drawn to vlogging to connect to others. Vlogging also
      served as a medium for combat veterans to tell their stories, position these
      stories against others' experiences, and engage in outreach and advocacy.
      Finally, milvlogs may provide an easily accessible resource for developing
      preventive and/or mental health treatment/support links.

PMID- 30196749
TI  - Prion-based nanomaterials and their emerging applications.
AB  - Protein misfolding and aggregation into highly ordered fibrillar structures have
      been traditionally associated with pathological processes. Nevertheless, nature
      has taken advantage of the particular properties of amyloids for functional
      purposes, like in the protection of organisms against environmental changing
      conditions. Over the last decades, these fibrillar structures have inspired the
      design of new nanomaterials with intriguing applications in biomedicine and
      nanotechnology such as tissue engineering, drug delivery, adhesive materials,
      biodegradable nanocomposites, nanowires or biosensors. Prion and prion-like
      proteins, which are considered a subclass of amyloids, are becoming ideal
      candidates for the design of new and tunable nanomaterials. In this review, we
      discuss the particular properties of this kind of proteins, and the current
      advances on the design of new materials based on prion sequences.

PMID- 30196751
TI  - Does cardiology hold pharmacogenetics to an inconsistent standard? A comparison
      of evidence among recommendations.
AB  - Current guideline recommendations for pharmacogenetic testing for clopidogrel by
      the American Heart Association/American College of Cardiology (AHA/ACC)
      contradict the Clinical Pharmacogenetics Implementation Consortium and the US
      FDA. The AHA/ACC recommends against routine pharmacogenetic testing for
      clopidogrel because no randomized controlled trials have demonstrated that
      testing improves patients' outcomes. However the AHA/ACC and the National
      Comprehensive Cancer Network (NCCN) recommend other pharmacogenetic tests in the
      absence of randomized controlled trials evidence. Using clopidogrel as a case
      example, we compared the evidence for other pharmacogenetic tests recommended by
      the AHA/ACC and NCCN. In patients that received percutaneous coronary
      intervention, the evidence supporting pharmacogenetic testing for clopidogrel is
      stronger than other pharmacogenetic tests recommended by the AHA/ACC and NCCN.

PMID- 30196753
TI  - Risk of Synchronous and Metachronous Colorectal Cancer: Population-Based
      Estimates in Denmark with Focus on Non-Hereditary Cases Diagnosed After Age 50.
AB  - BACKGROUND AND AIMS: The risk of synchronous and metachronous colorectal cancer
      is influenced by heritable and environmental factors. As a basis for comparative
      studies, we provide population-based estimates of synchronous and metachronous
      colorectal cancer with a focus on non-heritable cases. MATERIAL AND METHODS:
      Based on data from national Danish cancer registers, we estimated the proportion
      of synchronous colorectal cancer and the incidence rates and risks for
      metachronous colorectal cancer in 28,504 individuals, who developed 577
      metachronous colorectal cancer above age 50. RESULTS: Synchronous colorectal
      cancer was diagnosed in 1.3% of the cases. The risk of metachronous colorectal
      cancer was associated with sex, tumor location, and age with the strongest
      influence from the latter. The incidence rate ratios for metachronous colorectal
      cancer ranged from above 6 in patients below age 65 to <1-3.2 in patients above
      age 65. The absolute risk of metachronous colorectal cancer was ?10% in patients
      below age 65 and 1.0%-8.0% in patients above age 65. CONCLUSION: Individuals who
      develop sporadic, non-inherited colorectal cancer above age 50 are at a
      significantly increased risk of metachronous colorectal cancer with risk
      estimates that are strongly affected by age. This observation underscores the
      need for development of targeted surveillance in the most common clinical subset
      of colorectal cancer.

PMID- 30196752
TI  - Elevated expression of NFE2L3 predicts the poor prognosis of pancreatic cancer
      patients.
AB  - : The highly malignant feature and difficulties for early diagnosis are the key
      reasons contributing to the poor prognosis of pancreatic cancer (PC) patients.
      NFE2L3 is a nuclear transcription factor, which has been reported an important
      biomarker of several tumors. But the role of NFE2L3 in PC remained undefined.
      Herein, through qPCR and immunohistochemistry, we found a significantly increased
      NFE2L3 in PC tissues as compared with adjacent non-tumor tissues. While reducing
      NFE2L3 expression suppressed the invasion abilities of PC cells, elevated NFE2L3
      was found associated with lymph node metastasis (P = 0.001; HR = 3.95; 95% CI:
      1.70 - 9.17) and advanced TNM stages (P < 0.001; HR = 4.06; 95% CI: 1.74 - 9.46).
      Consistently, data from both our two cohorts and the TCGA database revealed that
      higher NFE2L3 PC carriers had worse outcomes than those lower NFE2L3 expressers.
      Lastly, we confirmed the regulatory role of NFE2L3 on VEGFA, an important player
      involved in tumor angiogenesis. Collectively, our investigations suggested the
      oncogenic role of NFE2L3 in PC development and provided the rational for future
      adding NFE2L3 for the risk assessment of PC patients. ABBREVIATIONS: NFE2L3: NF
      E2-related factor 3; UHMK1: U2AF homology motif kinase 1; VEGFA: vascular
      endothelial growth factor A; GEO: gene expression omnibus; TCGA: The Cancer
      Genome Atlas; HPDE: human pancreas duct cells; OS: overall survival; IHC:
      immunohistochemistry; FFPE: formalin-fixed and paraffin-embedded; SEM: standard
      error of mean.

PMID- 30196755
TI  - Using the common-sense model to understand health outcomes for medically
      unexplained symptoms: a meta-analysis.
AB  - Consistent with the common-sense model of self-regulation, illness
      representations are considered the key to improving health outcomes for medically
      unexplained symptoms and illnesses (MUS). Which illness representations are
      related to outcomes and how they are related is not well understood. In response,
      we conducted a meta-analysis of the relationship between illness representations,
      self-management/coping, and health outcomes (perceived disease state,
      psychological distress, and quality of life) for patients with MUS. We reviewed
      23 studies and found that threat-related illness representations and emotional
      representations were related to worse health outcomes and more negative coping
      (moderate to large effect). Generally, increases in negative coping mediated
      (with a moderate to large effect) the relationship of threat/emotional illness
      representations and health outcomes. Protective illness representations were
      related to better health outcomes, less use of negative coping and greater use of
      positive coping (small to moderate effect). The relationship of protective
      illness representations to better health outcomes was mediated by decreases in
      negative coping (moderate to large effect) and increases in positive coping
      (moderate effect). Perceiving a psychological cause to the MUS was related to
      more negative health outcomes (moderate to large effect) and more negative
      emotional coping (small effect). The relationship of perceiving a psychological
      cause and more negative health outcomes was mediated by increases in negative
      emotional coping. Improving our understanding of how illness representations
      impact health outcomes can inform efforts to improve treatments for MUS. Our
      results suggest behavioural treatments should focus on reducing threat-related
      illness representations and negative coping.

PMID- 30196754
TI  - Nonreplicative functions of the origin recognition complex.
AB  - Origin recognition complex (ORC), a heteromeric six-subunit complex, is the
      central component of the eukaryotic pre-replication complex. Recent data from
      yeast, frogs, flies and mammals present compelling evidence that ORC and its
      individual subunits have nonreplicative functions as well. The majority of these
      functions, such as heterochromatin formation, chromosome condensation, and
      segregation are dependent on ORC-DNA interactions. Furthermore, ORC is involved
      in the control of cell division via its participation in centrosome duplication
      and cytokinesis. Recent findings have also demonstrated a direct interaction
      between ORC and mRNPs and highlighted an essential role of ORC in mRNA nuclear
      export. Along with the growth of evolutionary complexity of organisms, ORC
      complex functions become more elaborate and new functions of the ORC sub
      complexes and individual subunits have emerged.

PMID- 30196756
TI  - Predicting microRNA-disease associations using bipartite local models and hubness
      aware regression.
AB  - The development and progression of numerous complex human diseases have been
      confirmed to be associated with microRNAs (miRNAs) by various experimental and
      clinical studies. Predicting potential miRNA-disease associations can help us
      understand the underlying molecular and cellular mechanisms of diseases and
      promote the development of disease treatment and diagnosis. Due to the high cost
      of conventional experimental verification, proposing a new computational method
      for miRNA-disease association prediction is an efficient and economical way.
      Since previous computational models ignored the hubness phenomenon, we presented
      a novel computational model of Bipartite Local models and Hubness-Aware
      Regression for MiRNA-Disease Association prediction (BLHARMDA). In this method,
      we first used known miRNA-disease associations to calculate the Jaccard
      similarity between miRNAs and between diseases, then utilized a modified kNNs
      model in the bipartite local model method. As a result, we effectively alleviated
      the detriments from 'bad' hubs. BLHARMDA obtained AUCs of 0.9141 and 0.8390 in
      the global and local leave-one-out cross validation, respectively, which
      outperformed most of the previous models and proved high prediction performance
      of BLHARMDA. Besides, the standard deviation of 0.0006 in 5-fold cross validation
      confirmed our model's prediction stability and the averaged prediction accuracy
      of 0.9120 showed the high precision of our model. In addition, to further
      evaluate our model's accuracy, we implemented BLHARMDA on three typical human
      diseases in three different types of case studies. As a result, 49 (Esophageal
      Neoplasms), 50 (Lung Neoplasms) and 50 (Carcinoma Hepatocellular) out of the top
      50 related miRNAs were validated by recent experimental discoveries.

PMID- 30196757
TI  - The Role of Dynamic Retinoscopy in Predicting Infantile Accommodative Esotropia
      and Influencing Emmetropization.
AB  - INTRODUCTION AND PURPOSE: To investigate the role that dynamic retinoscopy can
      play in reducing the occurrence of infantile accommodative esotropia and
      facilitating emmetropization in infants with high hyperopia. PATIENTS AND
      METHODS: 211 orthotropic infants under 1 year of age (3.5 to 12 months)
      identified as having >=5 diopters of hyperopia in their more hyperopic eye on a
      routine eye exam. On enrollment, infants underwent an assessment of accommodation
      using dynamic retinoscopy as well as a cycloplegic refraction. Infants who showed
      normal accommodation were followed without spectacles. If dynamic retinoscopy
      showed subnormal accommodation, partial hyperopic correction that allowed for
      full binocular accommodative responses at near were prescribed. Main outcome
      measures were the occurrence of esotropia, changes in refractive error, and
      visual acuity. RESULTS: Of the 211 infants enrolled, 146 showed normal
      accommodation and were followed without glasses (Group 1). None of these patients
      developed strabismus. Sixty-five patients showed subnormal accommodation and
      received partial hyperopic correction (Group 2). Thirty-four of the 65 (52%) in
      Group 2 did not develop strabismus (Group 2A) and 31 of the 65 (48%) developed
      strabismus (Group 2B). All 3 groups showed a reduction of hyperopia of 0.37D +/-
      0.25/year, 0.50D +/- 0.28/year, and 0.60D +/- 0.20/year in groups 1, 2A, and 2B,
      respectively. None of the differences between groups were statistically
      significant. CONCLUSIONS: Normal accommodation on dynamic retinoscopy in
      orthotropic hyperopic infants is a predictor of continued good alignment and such
      infants can be followed without spectacles. Partial spectacle correction based on
      dynamic retinoscopy may have a beneficial effect on reducing the development of
      strabismus without impeding emmetropization. Early binocular accommodative
      behavior seems to be predictive of infants at risk of developing strabismus.

PMID- 30196758
TI  - The Functional Benefits of Strabismus Surgery.
AB  - When performed prior to visual maturity, strabismus surgery can result in the
      development or recovery of binocularity. When strabismus surgery is performed
      after visual maturity, the functional benefits of the surgery should be
      dichotomized according to whether the onset of the strabismus was before or after
      visual maturity. If the onset was after visual maturity, patients typically are
      diplopic. Specific success rates for eliminating diplopia vary according to the
      nature of the strabismus; however, overall the success rate is quite high. There
      is a common misperception that surgery in adults for strabismus that began prior
      to visual maturity is merely cosmetic. Numerous studies contradict this
      misconception. Even if the strabismus has been longstanding, most adults will
      experience some improvement in binocular function after strabismus surgery. In
      esotropic patients, this improvement typically takes the form of an expansion of
      binocular visual fields; however, some patients may also regain stereopsis. There
      are many psychosocial benefits to adult strabismus surgery. This is reflected in
      the finding that the majority of adults surveyed with strabismus would trade a
      portion of their life expectancy to be rid of their strabismus.

PMID- 30196759
TI  - Re-Operation Strategies in Strabismus-Cooper's Dictum Amended.
AB  - PURPOSE: To outline a systematic approach to strabismus reoperations. Many
      strabismologists have a formulaic approach to strabismus reoperations, e.g.,
      treat it as a fresh case, advance previously recessed muscles to the original
      insertion, etc. Patients and methods: This paper is a collection of pearls gained
      from the author's 40+ years in practice. RESULTS: Effective strategies for
      strabismus reoperations are not formulaic and should be tailored to the specific
      history and findings of the patient. The first, and most important decision, is
      whether to operate on previously operated muscles or fresh muscles. This should
      be influenced, in part, by whether one is treating an overcorrection or
      undercorrection. Limitations of rotations and incomitance patterns should be
      addressed. Many important decisions should be made intraoperatively based on
      where muscles are found, their integrity (slipped in the capsule, stretched scar,
      etc.), repeated intraoperative forced ductions, and spring back balance testing.
      CONCLUSION: A proper plan for a strabismus reoperation takes into account a
      number of preoperative factors, and the surgeon should be prepared to modify the
      plan based on intraoperative findings.

PMID- 30196760
TI  - Pharmacogenetic impact of docetaxel on neoadjuvant treatment of breast cancer
      patients.
AB  - AIM: This study aimed to investigate the effect of CYP3A4 and CYP3A5 genotypes on
      clinical outcomes of docetaxel treatment. PATIENTS & METHODS: In the PROMIX
      trial, 150 breast cancer patients received docetaxel preoperatively. CYP3A4 and
      CYP3A5 genotype combinations were transformed into total CYP 3A phenotypes.
      RESULTS: Seven patients were characterized as poor metabolizer (PM), 22 patients
      as extensive metabolizer and 121 patients as intermediate metabolizer. The
      frequency of grade 3/grade 4 adverse events was higher in the PM group (p =
      0.002). One PM subject who basically lacked enzyme activity died from typhlitis.
      Total 45 recurrences were reported after a median of 5-year follow-up; none of
      these was PM. CONCLUSION: The allelic variants CYP3A4*22 and CYP3A5*3 contribute
      to the interpatient variations of docetaxel.

PMID- 30196761
TI  - Impact of military type footwear and load carrying workload on postural
      stability.
AB  - Postural stability has been shown to be impacted by footwear and task performed.
      This study analysed the impact of two military footwear, standard boot (STB) and
      minimalist boot (MTB) on postural stability, before (PRE) and after (POST) a load
      carriage task. Sixteen participants were tested for postural stability using
      sensory organisation and motor control tests on Neurocom EquitestTM. Postural
      sway, equilibrium scores and postural latencies were analysed using a two-factor
      repeated measures ANOVA: boot type (STB-MTB) * time (PRE-POST) load carriage
      task. Significantly greater postural sway variables, lower balance scores and
      slower postural latencies were seen in STB and POST load carriage conditions (p <
      .05). The results suggest that MTB exhibited greater balance compared to STB in
      balance conditions that rely on somatosensory feedback and that balance is
      lowered after a load carriage task. Decrements in postural stability could be
      attributed to boot design characteristics and muscular exertion due to the load
      carriage task. Practitioner Summary: Maintaining optimal postural stability is
      crucial in military. Impact of military footwear types and load carriage task on
      postural stability are addressed. Findings provide footwear design and physical
      exertion implications on postural stability leading to potential interventions
      that reduce postural stability decrements; thereby, reducing potential falls and
      fall related injuries.

PMID- 30196762
TI  - "We Don't Want to Live Like This": The Lived Experience of Dislocation, Poor
      Health, and Homelessness for Western Australian Aboriginal People.
AB  - Many policy interventions have attempted to address the entrenched disadvantage
      of Aboriginal Australians1; however, sustained improvement in social, cultural,
      physical, and emotional well-being is not evident. This disadvantage is
      compounded by paternalistic practices which do not promote Aboriginal self
      determination or empowerment. This article presents the lived experience and
      voice of Aboriginal Australians spending time in parks in Perth, Western
      Australia. A community-based participatory action research approach informed by
      critical Indigenous methodologies involving collaboration between Aboriginal and
      non-Aboriginal service providers was used. Participants experienced disconnection
      from kin and country, serious risk to personal safety, homelessness, and
      problematic health; all related to, and intersecting with, time spent in the
      parks. The participants' narratives highlight the enduring impacts of
      colonization, dispossession, and racism. These lived experiences are situated
      within contexts of rising moral panic from politicians, residents and mass media,
      and siloed policy and service delivery responses.

PMID- 30196763
TI  - Eugene Louis Doyen (1859-1916): The Reformer of French Surgery.
AB  - Eugene Louis Doyen (1859-1916) is considered as the reformer of French surgery at
      the end of 19th and early 20th century. Although he had a short life, dying at
      the age of 57, he left his mark in the history of French medicine and especially
      surgery, not only because he introduced many new medical instruments but also for
      his innovative idea to introduce cinematography in surgical education, which is
      crucial until today in the education of every surgeon in the world.

PMID- 30196764
TI  - Intraoperative Neuromonitoring During Thyroid Surgery: The Effect of Surgical
      Positioning.
AB  - Intraoperative neuromonitoring during thyroid surgery has been used to
      successfully prevent permanent neurological injury by early identification of
      anatomical variants. Proper interpretation of neuromonitoring data requires
      knowledge of what factors might affect the data. In this study, we examined the
      effect of surgical positioning on the latency and amplitude of neural recordings
      made from the vocalis muscle during thyroid surgery. A retrospective review was
      performed of 145 patients who underwent thyroid surgery. Eighty-three had open
      cervical procedures, and 62 had robotic-assisted transaxillary procedures.
      Intraoperative neuromonitoring recordings were made by stimulation of the vagus
      and recurrent laryngeal nerves for both groups. Ultrasound measurements were made
      of a subset of the transaxillary patients immediately before and after arm
      positioning. Groups differed only on right-sided recordings. Patients with
      transaxillary surgeries had significantly shorter latencies evoked from the vagus
      nerve. We found that vagus nerve-evoked latencies were also correlated to
      ultrasound measurements of the nerves. Surgical positioning during thyroid
      surgery is a factor that may affect intraoperative neuromonitoring data and
      should be taken into account by the surgeon during interpretation.

PMID- 30196765
TI  - Maintaining "mianzi" and "lizi": Understanding the reasons for formality
      marriages between gay men and lesbians in China.
AB  - As a result of societal expectations and to avoid societal homophobia, many
      lesbians and gay men in China marry heterosexual partners and do not disclose
      their own sexual orientation. This study used qualitative methods to explore why
      gay men enter into such marriages of convenience. A total of 17 in-depth
      interviews were conducted with lesbians and gay men who had entered "formality
      marriages." All interviews were digitally recorded for transcription; transcripts
      were analyzed using grounded theory to determine themes. The reasons for engaging
      in formality marriage can be grouped into broad categories, including:
      maintaining mianzi (reputation) and lizi (inner reality), avoiding moral
      distress, social discrimination, working in tizhi (social systems), accounting
      for their social relationships, and fulfilling filial piety. From our model we
      can see growing up as a member of a minority sexual orientation group means being
      discriminated against and marginalized in the family, work place, community, and
      society at large. Formality marriages not only offer a way to maintain one's
      personal and family reputation ( mianzi) in different contexts, but also avoid
      moral distress and maintain a personal private sexual orientation ( lizi) with
      their own homosexual partner. Formality marriage serves as a compromise to ensure
      cultural continuity, and it harmonizes individuals' interpersonal relationships
      and traditional Chinese family values. Understanding the reasons for formality
      marriage practices can help health professionals to create public health
      campaigns to dispel stereotypes and stigma about homosexuality, and to develop
      culturally sensitive services for homosexual populations.

PMID- 30196766
TI  - Urban Waste Collectors in Belo Horizonte, Brazil: Their Perceptions of
      Occupational Health Risk.
AB  - Frequent contact with hazardous materials makes waste collection a potentially
      unhealthy activity. This article assesses the perception of waste management
      workers regarding work-related accidents in domestic and health service contexts
      in Brazil. Six focus groups were performed between June 2014 and August 2015. The
      aims of this study were to apprehend different aspects of the participants'
      health, workers' experiences of work-related accidents and perception of risks.
      Cuts and puncture injuries were reported most frequently in the line of work and
      were often considered as irrelevant. Immunization against hepatitis B was not
      common among all workers, which increases the risk of infection for those
      individuals. Finally, it is considered urgent to consolidate an inclusive space
      in which workers can have discussions on their health.

PMID- 30196767
TI  - Stapled Transperineal Fistula Repair of Rectovaginal Fistula: A Preliminary
      Experience.
AB  - PURPOSE: This study is designed to assess the safety, efficacy, and postoperative
      outcomes of stapled transperineal repair in management of rectovaginal fistula
      (RVF). METHODS: A prospective database of patients with RVF undergoing stapled
      transperineal repair between May 2015 and December 2017 was established and
      studied retrospectively. RESULTS: Seven consecutive RVF patients underwent
      stapled transperineal repair. The mean operative time was 119 +/- 42 minutes. The
      estimated blood loss during operation was 24 +/- 14 mL. Concomitant levatorplasty
      was performed with 4 patients and sphincteroplasty with 2 patients. Over a median
      follow-up of 6 months (range 3-33 months), no case was encountered with
      recurrence. The mean postoperative Wexner score was significantly improved when
      compared with the preoperative scores (mean preoperative vs postoperative Wexner
      scores 3 [range 3-4] vs 1 [range 1-2], respectively; P = .01). CONCLUSIONS:
      Stapled transperineal repair of RVF appears safe and effective. The initial
      results are encouraging, suggesting the need for a more formal prospective
      assessment of this technique as part of a randomized trial for the management of
      low- and mid-vaginal fistulas.

PMID- 30196768
TI  - OneShot-M: A New Device for Close Laparoscopy Pneumoperitoneum.
AB  - INTRODUCTION: The induction of pneumoperitoneum is the first and most critical
      phase of laparoscopy, due to the significant risk of serious vascular and
      visceral complications. The closed technique for the creation of pneumoperitoneum
      could lead to several surgical complications. The present study aimed to overcome
      the complications associated with the insertion of Veress needle, improving its
      use, and facilitating the rapid creation of pneumoperitoneum. METHODS: Thirty
      large white female pigs were enrolled in our study. A common plunger was modified
      in order to allow the passage of a 15-cm long Veress needle. This method was
      applied to 26 laparoscopic procedures (26 pigs) of several specialist branches.
      RESULTS: OneShot-M close laparoscopy pneumoperitoneum creation device allowed us
      to obtain pneumoperitoneum quickly in all attempts, without any intraoperative
      and postoperative complications related to the use of the Veress needle.
      CONCLUSION: The use of the proposed device showed an induction time as quick as
      the standard laparoscopic closed abdominal entry. The patented device is cheap
      and allows a safe abdominal entry. In addition, abdominal entry is much faster
      than the classic open technique.

PMID- 30196769
TI  - Evaluation of the New ISGLS Definitions of Typical Posthepatectomy Complications.
AB  - BACKGROUND AND OBJECTIVES: The International Study Group of Liver Surgery
      established the first internationally standardized definitions and grading for
      posthepatectomy hemorrhage, posthepatectomy liver failure, and bile leakage. We
      aimed to correlate these definitions and grades of complications with objective
      parameters of the postoperative course, namely, mortality and length of stay, to
      assess the usefulness in clinical routine. METHODS: A total of 415 patients
      underwent hepatic surgery between 2004 and 2014. Uni- and multivariate analyses
      were made for correlations of posthepatectomy hemorrhage, posthepatectomy liver
      failure, and bile leakage with perioperative parameters and mortality. RESULTS:
      Of the total, 25 (6.1%) patients developed a posthepatectomy hemorrhage Grade A,
      3 (0.7%) patients a posthepatectomy hemorrhage Grade B, and 1 (0.2%) patient a
      posthepatectomy hemorrhage Grade C; 23 (5.5%) patients had a posthepatectomy
      liver failure Grade A, 24 (5.8%) patients a posthepatectomy liver failure Grade
      B, and 7 patients (1.6%) a posthepatectomy liver failure Grade C. Bile leakage
      Grade A occurred in 10 (2.4%) patients, bile leakage Grade B in 24 (5.8%)
      patients, and bile leakage Grade C in 7 (1.6%) patients. Mortality was
      significantly increased in patients with posthepatectomy hemorrhage Grades B and
      C and in patients with posthepatectomy liver failure Grades A, B, and C. Three
      (42.9%) patients with bile leakage Grade C died. CONCLUSION: Our data indicate
      that the new definitions correlate well with mortality and duration of hospital
      stay.

PMID- 30196770
TI  - Autologous Fat Transfer After Augmentation and Reconstruction of the Female
      Breast: An International, Cross-Sectional Photo-Comparison Study Among Different
      Physician and Laymen Study Groups.
AB  - OBJECTIVE: The aim of this study is to compare the cosmetic evaluation of
      autologous fat transfer (AFT) for various indications between surgeons and
      different laymen groups. BACKGROUND DATA: Despite the upsurge in AFT
      scientific/clinical interest, objectifying satisfaction has only recently
      progressed beyond simple Likert-type/Visual Analog Scales. Furthermore,
      differences in satisfaction between laymen and surgeons has not been thoroughly
      studied. METHOD: A photo comparison study between European plastic surgeons and
      different laymen groups was conducted to investigate agreement on cosmetic
      evaluation of AFT. Three sets of preoperative/postoperative photographs
      illustrating patients treated with External Vacuum Expansion (EVE) + AFT for
      various indications in breast surgery were scored according to the Harris Scale,
      and the interrater agreement was analyzed using Cohen's kappa. RESULTS: The
      overall agreement between the surgeons and the groups of former augmentation,
      control group, and deep inferior epigastric artery perforator patients was fair,
      moderate, and substantial, respectively. Interrater agreements among different
      laymen groups and surgeons from different countries among themselves was
      substantial to almost perfect. Finally, we found that laymen are generally more
      optimistic about postoperative results than surgeons. CONCLUSION: In our study,
      former augmentation patients showed the lowest agreement with surgeons, in the
      cosmetic appreciation of EVE + AFT and this group might benefit from a more
      thorough preoperative consultation regarding expectations when choosing AFT.
      However, overall laymen tend to be more optimistic about postoperative results
      and surgeon education in general does not seem influenced by surgeon nationality.
      The significant differences between surgeons and laymen in the cosmetic
      evaluation of EVE + AFT justifies further studies that focus on the qualitative
      aspects of these differences to further balance patients' and surgeons'
      expectations.

PMID- 30196771
TI  - Cyclooxygenase-2 interacts with MMP and FGF pathways to promote epimorphic
      regeneration in lizard Hemidactylus flaviviridis.
AB  - Cyclooxygenase-2 (COX-2) is an inducible enzyme known for its role in promoting
      inflammation, pain and cancer. It has more recently been attributed a function in
      epimorphic regeneration of vertebrate appendages. However, its position among the
      molecular regulators of regeneration remains unclear. This work was aimed at
      analyzing the influence of COX-2 on critical mediators of regenerative processes
      in the lizard Hemidactylus flaviviridis. It was found during the early events of
      regeneration that MMP and FGF genes get altered in their expression in response
      to administration of etoricoxib, a COX-2 inhibitor. Results herein also reflect a
      positive correlation between COX-2 activity and gelatinase activities in our
      system. These observations, for the first time, establish a definitive
      interaction of the COX-2 signal with the MMPs and FGFs as essential to the
      initiation of tail regeneration, placing it as one of the top regulators of the
      molecular events which characterize epimorphosis.

PMID- 30196773
TI  - What's In A Name?

PMID- 30196772
TI  - Effect of adipocyte-derived IGF-I on adipose tissue mass and glucose metabolism
      in the Berlin Fat Mouse.
AB  - Besides liver, IGF-I is expressed in adipose tissue. However, the effects of this
      local IGF-I on adipose tissue and metabolism are unclear. We generated adipocyte
      specific knock-out mice on the background of the Berlin Fat Mouse Inbred (BFMI)
      line to evaluate the contribution of adipocyte-IGF-I on glucose metabolism and
      adipose tissue development. BFMI mice are obese, non-diabetic with elevated
      plasma insulin and IGF-I concentration. The knock-out in adipocytes led to a
      total white adipose tissue expression of 50-60% due to unaltered Igf-1 expression
      in stromavascular cells. The lack of IGF-I from adipocytes did not alter plasma
      IGF-I concentration. BFMIChr3-Igf-I-KOQ-AT mice had reduced adipose tissue mass
      in most depots. During oral glucose tolerance tests, BFMIChr3-Igf-I-KOQ-AT mice
      showed an impaired glucose clearance (p = .03). Interestingly, insulin action was
      enhanced during insulin tolerance tests (p = .05). In conclusion, adipocyte
      specific IGF-I ablation in obese BFMI mice results in reduced adipose tissue mass
      and thereby alters glucose metabolism.

PMID- 30196774
TI  - Looking Forward but Glancing Backward.

PMID- 30196775
TI  - Ophthalmoplegia: When the Eyes Don't Move: An Introduction.

PMID- 30196776
TI  - Ophthalmoplegia and Congenital Cranial Dysinnervation Disorders.
AB  - Some forms of ophthalmoplegia are congenital and fall into the category of
      Congenital Cranial Dysinnervation Disorders (CCDDs). These disorders arise from a
      primary defect of cranial nucleus/nerve development or guidance. Many have
      substantial limitations of ocular motility with or without other associated
      features. The type and degree of ophthalmoplegia can be similar between CCDD
      subtypes as well as with non-congenital forms of ophthalmoplegia. Therefore
      diagnostic confirmation often requires neuro-imaging and/or genetic
      investigations. The clinician should consider this category in cases of
      ophthalmoplegia that are congenital and nonprogressive in nature.

PMID- 30196777
TI  - Ophthalmoplegia: Definition and Clinical Diagnostic Techniques.
AB  - Ophthalmoplegia can be caused by multiple etiologies. There are restrictive,
      paretic, neurologic, and myasthenic conditions that can lead to reduced mobility
      of the eyes that at first glance may be difficult to discern from one another.
      While the examiner may be tempted to order various lab tests and scans to reach a
      diagnosis, the assessment of ophthalmoplegia by clinical examination alone can
      often provide enough information to determine the etiology, or at least rule out
      causes that can spare the patient and facility from unnecessary time-consuming
      and costly tests. This article will discuss the definition of ophthalmoplegia as
      well as various techniques that can be performed in the clinical setting that may
      help distinguish its underlying causes.

PMID- 30196778
TI  - Infantile and Early Acquired Ophthalmoplegic Syndromes.
AB  - Ophthalmoplegia is rare in infants and may present either as a static or a
      progressing deficit. In this report, I will summarize the major causes of
      ophthalmoplegia when it presents in infancy or early childhood. Strategies for
      narrowing the differential diagnosis will also be considered.

PMID- 30196779
TI  - The Non-surgical Management of Ophthalmoplegia.
AB  - Ophthalmoplegia can result from damage or dysfunction of the supranuclear eye
      movement pathways, the brainstem internuclear pathways, or the ocular motor
      nerves. Diplopia and impaired eye movements are commonly associated symptoms. The
      goal of non-surgical treatment is usually management of symptoms, and the primary
      tool used is prism. Results of recent studies in the neurorehabilitation
      literature have suggested that eye muscle exercise may do more than compensate
      for symptoms of ophthalmoplegia. They may accelerate recovery for those
      conditions in which recuperation is possible, and restore ocular mobility in
      chronic and degenerative conditions. A large, randomized, blind study is needed
      to investigate the efficacy of eye exercises in ophthalmoplegia.

PMID- 30196780
TI  - What Did They Know Then? A Journey Among the Giants of the Past.
AB  - Dr. Richard Scobee has the honorary title "The Father of American Orthoptics." In
      addition to his numerous accomplishments in his academic career, he had hobbies
      that included collecting historical stamps. In tribute to his love of things
      past, this lecture will delve into the remote history of ophthalmology, to see
      what eminent pioneers knew and wrote about eye muscle disorders and binocular
      vision in their treatises. Our journey will include eight personalities and their
      works, ranging from the 7th century through to the early 19th century, and will
      encompass Europe, the Middle East, Great Britain, and North America. Analyzing
      the writings of these masters affords glimpses into the knowledge base and
      philosophies that were prevalent in different centuries. Many of these
      individuals were innovators who pushed the boundaries of knowledge. Some of them
      made advances using intuition and reason, mainly through case experience and case
      studies, while others used the scientific method to gain new information. In many
      cases, the words written by these luminaries centuries ago still resonate with us
      today and guide us in our everyday practices. It is hoped that this journey will
      be enlightening for orthoptists, ophthalmologists, and allied health personnel,
      and confirm, as in many areas of science, that we truly stand on the shoulders of
      giants, the masters from the recent and the distant past.

PMID- 30196781
TI  - Acquired Ophthalmoplegia in Older Children and Adults.
AB  - Ophthalmoplegia or ophthalmoparesis are the terms given to paralysis or paresis
      of one or more of the extraocular muscles in one or both eyes. It may be
      representative of serious neurological or systemic disease. Other mechanisms may
      cause limitation of eye movement, including restrictive or myasthenic conditions,
      or combinations of several etiologies. Evaluating and differentiating the
      mechanisms causing ophthalmoplegia is important in determining the correct
      diagnosis and selecting the appropriate management in these complex cases.

PMID- 30196782
TI  - Red Flags in the Assessment of Adult Ophthalmoplegia.
AB  - Acquired ophthalmoplegia can represent a harbinger of vision and life-threatening
      disease. Recognition of select clinical "red flags" on history or examination can
      facilitate early diagnosis. This article reviews relevant clinical pearls for the
      detection of dire causes of acquired ophthalmoplegia in adults including
      myasthenia gravis, carotid cavernous fistula, giant cell arteritis, and thiamine
      deficiency. Prompt treatment of all of these disorders can either reverse or halt
      the progression of visual manifestations.

PMID- 30196783
TI  - Surgical Management of Ophthalmoplegia.
AB  - Surgical management-depending upon the severity of the ophthalmoplegia-ranges
      from restorative to palliative. In paresis with reasonable residual muscle
      function and ductions, the goal of the surgery is not only to restore single
      vision in primary position but also to provide a relatively normal field of
      single binocular vision. With complete paralysis of a single muscle or more than
      one muscle served by a single cranial nerve (third), in addition to conventional
      recess or resect surgery, the transposition of still-functioning muscles is often
      needed to obtain a durable result and restore at least some field of single
      binocular vision. In complete ophthalmoplegia, the benefits of the surgery are
      limited; but even in these cases, surgery can often reduce the need for an
      awkward head posture and improve appearance.

PMID- 30196784
TI  - Isolated Ocular Motor Nerve Palsies.
AB  - Isolated cranial nerve (CN) palsies are frequently encountered by
      strabismologists. Management decisions for patients with isolated ocular motor
      nerve palsies must take into account multiple factors, including patient age,
      historical features, the specific CN affected, examination findings, and
      coexistent medical diagnoses. In general, isolated ocular motor nerve palsies in
      children are assessed and managed differently than adults. Furthermore, older
      adults with vascular risk factors may be managed differently than younger adults
      and children. The need for urgent neuroimaging in older adults with microvascular
      risk factors is under debate and requires the physician to weigh the risks and
      benefits of close observation with immediate testing. The presence of multiple
      cranial neuropathies should also raise the level of concern and indicate the need
      for a more urgent work-up. The following manuscript aims to provide information
      on common etiologies of isolated ocular motor nerve palsies and to suggest
      algorithms for the management of these CN palsies in children and adult.

PMID- 30196785
TI  - Spasm of the Near Reflex: Literature Review and Proposed Management Strategy.
AB  - BACKGROUND AND PURPOSE: Spasm of the near reflex (SNR) can be a variable,
      unpredictable condition. There is no standard management strategy. The purpose of
      this paper is to summarize the pertinent information from a literature review to
      better identify, explain, and manage this condition. PATIENTS AND METHOD: Case
      presentations and retrospective literature review Results: The presumed cause of
      SNR can be grouped into four categories: psychogenic, head trauma,
      organic/neurologic, and other causes. Etiology is often presumed rather than
      confirmed and may be multifactorial. A number of treatments have been reported,
      all with unpredictable efficacy.Etiology may be the most important factor in
      predicting treatment outcomes. In general, SNR due to psychogenic causes often
      has a good prognosis but time required for resolution varies widely. SNR due to
      an organic/neurologic cause may resolve with treatment of the underlying
      condition, but a psychogenic component may also occur in these cases. SNR due to
      head trauma has the poorest prognosis with incomplete resolution for many.
      CONCLUSION: SNR is highly variable in presentation and may have various causes.
      Response to treatment is unpredictable but may be dependent on etiology. A
      standardized treatment protocol for SNR may not be attainable, but it is possible
      to approach management of SNR in a methodical manner. A proposed management
      strategy is presented.

PMID- 30196786
TI  - Double vision in adults.
AB  - PURPOSE: To determine the patient characteristics, patterns in presentation and
      incidences of the various etiologies in adult patients with the chief complaint
      of double vision. DESIGN: Retrospective review. SUBJECTS: All persons greater
      than 18 years of age who presented to a single provider (DG) in a nonacademic
      private practice over a 2-year period, from 2011 to 2013, with the chief
      complaint of double vision. The provider is part of a multispecialty eye care
      group practice with both ophthalmologists and optometrists. This group practice
      provides a large adult referral base. METHODS: Examination for each patient
      included refraction, versions, alignment in different positions of gaze at
      distance and at near, binocular sensory testing, neuro-ophthalmologic
      examination, and dilated fundus examination if not recently documented. Alignment
      was measured with cover-uncover testing and alternate cover testing with prism
      bars or free prisms, using Snellen letters for fixation. Appropriate refractive
      correction was ensured. Alignment was measured in the primary position at
      distance and in gaze directed 20 degrees L, R, up, and down. The near deviation
      was measured in the reading position with the large letters on a near card for
      fixation. Sensory testing was performed with the Worth 4-dot at distance and near
      and with the Titmus stereopsis test. Vectograph testing was also performed at
      distance on many patients, particularly those with small-angle deviations. The
      prismatic correction necessary to correct diplopia subjectively at distance in
      the primary position and at near in the reading position was also recorded.
      PRIMARY OUTCOME: Ocular alignment and etiology of diplopia. Management, response
      to treatment, and outcome were also recorded. RESULTS: A total of 125 patients
      were included in the analysis. Subjects ranged from 18 to 93 years of age. Most
      cases of idiopathic strabismus were in the elderly, but the age range varied with
      category of underlying strabismus. Small-angle HT was the most common type of
      strabismus, comprising 21% of all subjects. ET, usually of the divergence
      insufficiency type (20%); XT (14%); and palsies not including trochlear palsy
      (12%) and trochlear palsy (8%) were the next most common etiologies. No
      strabismus was found in 11% of subjects. CONCLUSIONS: Most cases of diplopia in
      adults presenting as an outpatient can be classified into a few categories based
      on their type of strabismus. These categories of strabismus share typical age
      ranges and features. While diplopia in adults is usually idiopathic, diplopia can
      be the presenting sign of serious underlying pathology. Thus, a thorough history;
      examination; and, in some cases, diagnostic testing is necessary.

PMID- 30196788
TI  - Ad-hoc Reviewers 2017-2018.

PMID- 30196787
TI  - Orbital Imaging in Strabismus.
AB  - Normal orbital anatomy plays a foundational role in stabilizing binocular eye
      movements. Abnormal orbital anatomy, contrariwise, destabilizes binocular eye
      alignment by introducing eccentric and unbalanced EOM forces. These abnormalities
      can be categorized into five broad etiologies: (1) orbital structural disorders;
      (2) globe size disorders; (3) degenerative disorders; (4) innervational
      disorders; and (5) trauma. Orbital imaging provides important diagnostic
      information on EOM path and innervational status, but only if performed properly.
      The three critical elements are (1) maximize the field of view by focusing on the
      orbit of interest; (2) control gaze, ideally imaging in primary position; and (3)
      image perpendicular (direct coronals) and parallel (axial for horizontal,
      sagittal for vertical) to the EOM(s) of interest. Images should be analyzed
      systematically by comparing EOM size and location between orbits and with
      established normative values. The single most critical image is the most anterior
      direct coronal plane that contains both globe and clearly defined EOM cross
      sections. EOM positional abnormalities in this plane establish the diagnosis for
      the first three categories of orbital abnormalities. Innervational abnormalities
      are best evaluated in the mid-orbit; asymmetry in mid-orbital EOM size and shape
      defines or confirms innervational disorders like complete or partial cranial
      nerve palsies.

PMID- 30196789
TI  - The AtRial Cardiopathy and Antithrombotic Drugs In prevention After cryptogenic
      stroke randomized trial: Rationale and methods.
AB  - : Rationale Recent data suggest that a thrombogenic atrial substrate can cause
      stroke in the absence of atrial fibrillation. Such an atrial cardiopathy may
      explain some proportion of cryptogenic strokes. Aims The aim of the ARCADIA trial
      is to test the hypothesis that apixaban is superior to aspirin for the prevention
      of recurrent stroke in subjects with cryptogenic ischemic stroke and atrial
      cardiopathy. Sample size estimate 1100 participants. Methods and design Biomarker
      driven, randomized, double-blind, active-control, phase 3 clinical trial
      conducted at 120 U.S. centers participating in NIH StrokeNet. Population studied
      Patients >= 45 years of age with embolic stroke of undetermined source and
      evidence of atrial cardiopathy, defined as >= 1 of the following markers: P-wave
      terminal force >5000 uV * ms in ECG lead V1, serum NT-proBNP > 250 pg/mL, and
      left atrial diameter index >= 3 cm/m2 on echocardiogram. Exclusion criteria
      include any atrial fibrillation, a definite indication or contraindication to
      antiplatelet or anticoagulant therapy, or a clinically significant bleeding
      diathesis. INTERVENTION: Apixaban 5 mg twice daily versus aspirin 81 mg once
      daily. ANALYSIS: Survival analysis and the log-rank test will be used to compare
      treatment groups according to the intention-to-treat principle, including
      participants who require open-label anticoagulation for newly detected atrial
      fibrillation. Study outcomes The primary efficacy outcome is recurrent stroke of
      any type. The primary safety outcomes are symptomatic intracranial hemorrhage and
      major hemorrhage other than intracranial hemorrhage. Discussion ARCADIA is the
      first trial to test whether anticoagulant therapy reduces stroke recurrence in
      patients with atrial cardiopathy but no known atrial fibrillation.

PMID- 30196790
TI  - Elevated C-reactive protein increases diagnostic accuracy of algorithm-defined
      stroke-associated pneumonia in afebrile patients.
AB  - Background and aim Pyrexia-dependent clinical algorithms may under or
      overdiagnose stroke-associated pneumonia. This study investigates whether
      inclusion of elevated C-reactive protein as a criterion improves diagnosis.
      Methods The contribution of C-reactive protein  >=30 mg/l as an additional
      criterion to a Centers for Disease Control and Prevention-based algorithm
      incorporating pyrexia with chest signs and leukocytosis and/or chest infiltrates
      to diagnose stroke-associated pneumonia was assessed in 1088 acute stroke
      patients from 37 UK stroke units. The sensitivity, specificity, and positive
      predictive value of different approaches were assessed using adjudicated stroke
      associated pneumonia as the reference standard. Results Adding elevated C
      reactive protein to all algorithm criteria did not increase diagnostic accuracy
      compared with the algorithm alone against adjudicated stroke-associated pneumonia
      (sensitivity 0.74 (95% CI 0.65-0.81) versus 0.72 (95% CI 0.64-0.80), specificity
      0.97 (95% CI 0.96-0.98) for both; kappa 0.70 (95% CI 0.63-0.77) for both). In
      afebrile patients (n = 965), elevated C-reactive protein with chest and
      laboratory findings had sensitivity of 0.84 (95% CI 0.67-0.93), specificity of
      0.99 (95% CI 0.98-1.00), and kappa 0.80 (95% CI 0.70-0.90). The modified
      algorithm of pyrexia or elevated C-reactive protein and chest signs with
      infiltrates or leukocytosis had sensitivity of 0.94 (95% CI 0.87-0.97),
      specificity of 0.96 (95% CI 0.94-0.97), and kappa of 0.88 (95% CI 0.84-0.93)
      against adjudicated stroke-associated pneumonia. Conclusions An algorithm
      consisting of pyrexia or C-reactive protein >=30 mg/l, positive chest signs,
      leukocytosis, and/or chest infiltrates has high accuracy and can be used to
      standardize stroke-associated pneumonia diagnosis in clinical or research
      settings. Trial Registration http://www.isrctn.com/ISRCTN37118456.

PMID- 30196791
TI  - Incidence of atrial fibrillation among patients with an embolic stroke of
      undetermined source: Insights from insertable cardiac monitors.
AB  - Background Prophylactic use of direct oral anticoagulants for recurrent stroke
      prevention in patients with embolic strokes of undetermined source is currently
      being investigated. It is uncertain whether the bleeding risks associated with
      prophylactic direct oral anticoagulants use will outweigh any stroke prevention
      benefit in embolic strokes of undetermined source patients who lack underlying
      atrial fibrillation. Methods We determined the proportion of cryptogenic stroke
      patients in the CRYSTAL atrial fibrillation trial who met inclusion criteria for
      the NAVIGATE embolic stroke of undetermined source and RE-SPECT embolic stroke of
      undetermined source trials and their atrial fibrillation incidence. Both embolic
      strokes of undetermined source trials impose requirements on age, modified Rankin
      Score, antiplatelet use, and type of infarction. Insertable cardiac monitors were
      used to determine the atrial fibrillation detection rates at 30 days and 3 years
      using Kaplan-Meier's estimates. Results Among 441 patients enrolled in the
      CRYSTAL atrial fibrillation trial, 189 (42.9%) and 236 (53.5%) met the inclusion
      criteria of the NAVIGATE embolic stroke of undetermined source and RE-SPECT
      embolic stroke of undetermined source trials, respectively. Atrial fibrillation
      detection rates at 3 years among insertable cardiac monitors patients eligible
      for the NAVIGATE embolic stroke of undetermined source and RE-SPECT embolic
      stroke of undetermined source trials were 35.8% and 33.6% while detection rates
      at 30 days were 5.6% and 3.5%, respectively. Conclusion Only half of cryptogenic
      stroke patients in CRYSTAL atrial fibrillation met the inclusion criteria for the
      ongoing embolic strokes of undetermined source trials. Approximately, two-thirds
      of patients with embolic strokes of undetermined source do not have any atrial
      fibrillation despite continuous rhythm monitoring for up to three years. The
      benefits of prophylactic use of direct oral anticoagulants in the absence of
      atrial fibrillation is unknown and therefore embolic strokes of undetermined
      source patients could benefit from prolonged atrial fibrillation monitoring until
      more robust data are available. ClinicalTrials.gov Registration NCT00924638.
      https://clinicaltrials.gov/ct2/show/NCT00924638 .

PMID- 30196792
TI  - A protocol for precise comparisons of small vessel disease lesions between ex
      vivo magnetic resonance imaging and histopathology.
AB  - Rationale Neuroimaging and clinical studies have defined human sporadic cerebral
      small vessel disease but the pathophysiology remains relatively poorly
      understood. To develop effective therapies and preventative strategies, we must
      better understand the heterogeneity and development of small vessel disease at a
      cellular level. Hypothesis Small vessel disease lesions as seen on neuroimaging
      have specific neuropathological correlates. Methods and design Standard
      histological samples are taken from strategic areas of the brain typically
      affected by small vessel disease, in cases with a range of disease from mild to
      severe and controls. Tissue is formalin fixed, scanned using 7-tesla magnetic
      resonance imaging and processed for histology. Histological slides are
      digitalized then registered with the corresponding magnetic resonance image.
      Small vessel disease burden is assessed and lesions are precisely identified on
      the ex vivo imaging and microscopy independently then compared. The tissue can be
      interrogated using multiple magnetic resonance sequences and histological methods
      targeting the gliovascular unit. Study outcomes The primary outcome is
      identifying and defining the cellular characteristics of small vessel disease
      lesions compared to imaging. Secondary outcomes are related to obtaining
      information about abnormalities of protein expression in the gliovascular unit,
      defining groups of small vessel disease severity in our cohorts for future
      analysis and developing a reliable, reproducible protocol for accurate
      radiological-histological lesion comparison, which can be applied to other
      neurological diseases in the future. Discussion Comprehensive, precise
      pathological-radiological-clinical correlations in small vessel disease will
      provide greater insight into associations and pathophysiology underlying magnetic
      resonance imaging findings in normal- and abnormal-appearing tissue, ex vivo and
      in vivo.

PMID- 30196793
TI  - Modern and traditional approaches combined into an effective gray-box
      mathematical model of full-blood acid-base.
AB  - BACKGROUND: The acidity of human body fluids, expressed by the pH, is
      physiologically regulated in a narrow range, which is required for the proper
      function of cellular metabolism. Acid-base disorders are common especially in
      intensive care, and the acid-base status is one of the vital clinical signs for
      the patient management. Because acid-base balance is connected to many bodily
      processes and regulations, complex mathematical models are needed to get insight
      into the mixed disorders and to act accordingly. The goal of this study is to
      develop a full-blood acid-base model, designed to be further integrated into more
      complex human physiology models. RESULTS: We have developed computationally
      simple and robust full-blood model, yet thorough enough to cover most of the
      common pathologies. Thanks to its simplicity and usage of Modelica language, it
      is suitable to be embedded within more elaborate systems. We achieved the
      simplification by a combination of behavioral Siggaard-Andersen's traditional
      approach for erythrocyte modeling and the mechanistic Stewart's physicochemical
      approach for plasma modeling. The resulting model is capable of providing
      variations in arterial pCO2, base excess, strong ion difference, hematocrit,
      plasma protein, phosphates and hemodilution/hemoconcentration, but insensitive to
      DPG and CO concentrations. CONCLUSIONS: This study presents a straightforward
      unification of Siggaard-Andersen's and Stewart's acid-base models. The resulting
      full-blood acid-base model is designed to be a core part of a complex dynamic
      whole-body acid-base and gas transfer model.

PMID- 30196794
TI  - Updated cost-effectiveness and risk-benefit analysis of two infant rotavirus
      vaccination strategies in a high-income, low-endemic setting.
AB  - BACKGROUND AND OBJECTIVE: Since 2013, a biennial rotavirus pattern has emerged in
      the Netherlands with alternating high and low endemic years and a nearly 50%
      reduction in rotavirus hospitalization rates overall, while infant rotavirus
      vaccination has remained below 1% throughout. As the rotavirus vaccination cost
      effectiveness and risk-benefit ratio in high-income settings is highly influenced
      by the total rotavirus disease burden, we re-evaluated two infant vaccination
      strategies, taking into account this recent change in rotavirus epidemiology.
      METHODS: We used updated rotavirus disease burden estimates derived from (active)
      surveillance to evaluate (1) a targeted strategy with selective vaccination of
      infants with medical risk conditions (prematurity, low birth weight, or
      congenital conditions) and (2) universal vaccination including all infants. In
      addition, we added herd protection as well as vaccine-induced intussusception
      risk to our previous cost-effectiveness model. An age- and risk-group structured,
      discrete-time event, stochastic multi-cohort model of the Dutch pediatric
      population was used to estimate the costs and effects of each vaccination
      strategy. RESULTS: The targeted vaccination was cost-saving under all scenarios
      tested from both the healthcare payer and societal perspective at rotavirus
      vaccine market prices (?135/child). The cost-effectiveness ratio for universal
      vaccination was ?51,277 at the assumed vaccine price of ?75/child, using a
      societal perspective and 3% discount rates. Universal vaccination became cost
      neutral at ?32/child. At an assumed vaccine-induced intussusception rate of
      1/50,000, an estimated 1707 hospitalizations and 21 fatal rotavirus cases were
      averted by targeted vaccination per vaccine-induced intussusception case.
      Applying universal vaccination, an additional 571 hospitalizations and <  1
      additional rotavirus death were averted in healthy children per vaccine-induced
      intussusception case. CONCLUSION: While universal infant rotavirus vaccination
      results in the highest reductions in the population burden of rotavirus, targeted
      vaccination should be considered as a cost-saving alternative with a favorable
      risk-benefit ratio for high-income settings where universal implementation is
      unfeasible because of budget restrictions, low rotavirus endemicity, and/or
      public acceptance.

PMID- 30196795
TI  - Leukemic arthritis and severe hypercalcemia in a man with chronic myeloid
      leukemia: a case report and review of the literature.
AB  - BACKGROUND: Patients with chronic myeloid leukemia typically present with high
      white blood cell counts revealed during annual checkups. Leukemic arthritis and
      hypercalcemia are rare manifestations in patients with chronic myeloid leukemia.
      CASE PRESENTATION: A 35-year-old Thai man who had been diagnosed with chronic
      myeloid leukemia in the chronic phase developed blast crisis while he was
      receiving ongoing treatment with imatinib at 400 mg/day. Initially, he presented
      with oligoarthritis in both knees and ankles. A bone scintigraphy showed a
      prominent bony uptake, with a symmetrical, increased uptake in many bone areas.
      Induction therapy with a 7 + 3 induction regimen was prescribed in conjunction
      with 600 mg of imatinib once daily before switching to 140 mg of dasatinib. He
      subsequently developed severe hypercalcemia (total serum calcium of 17.8 mg/dL),
      with generalized osteolytic lesions detected on a bone survey. His serum vitamin
      D level was 50.64 ng/mL, while the serum parathyroid hormone level was 9.82
      pg/mL. Despite the administration of an aggressive intravenously administered
      hydration, intravenously administered calcitonin, and 600 mg/day of imatinib, the
      severe hypercalcemia was refractory. We therefore decided to prescribe 20 mg/day
      of intravenously administered dexamethasone; fortunately, his serum calcium level
      decreased dramatically to normal range within a few days. CONCLUSIONS: Although
      leukemic arthritis and severe hypercalcemia are extraordinary presentations in
      patients with chronic myeloid leukemia, the advanced phase of the disease might
      bring on these symptoms. Apart from parathyroid hormone-related protein-related
      hypercalcemia, vitamin D is a mechanism of humoral-mediated hypercalcemia.

PMID- 30196796
TI  - Women in Intensive Care study: a preliminary assessment of international data on
      female representation in the ICU physician workforce, leadership and academic
      positions.
AB  - BACKGROUND: Despite increasing female enrolment into medical schools, persistent
      gender gaps exist in the physician workforce. There are limited published data on
      female representation in the critical care medicine workforce. METHODS: To obtain
      a global perspective, societies (n = 84; 79,834 members (40,363 physicians,
      39,471 non-physicians)) registered with the World Federation of Societies of
      Intensive and Critical Care Medicine were surveyed. Longitudinal data on female
      trainee and specialist positions between 2006-2017 were obtained from Australia
      and New Zealand. Data regarding leadership and academic faculty representation
      were also collected from national training bodies and other organisations of
      critical care medicine. RESULTS: Of the 84 societies, 23 had a registered
      membership of greater than 500 members. Responses were received from 27 societies
      (n = 55,996), mainly high-income countries, covering 70.1% of the membership.
      Amongst the physician workforce, the gender distribution was available from six
      (22%) participating societies-mean proportion of females 37 +/- 11% (range 26
      50%). Longitudinal data from Australia and New Zealand between 2006 and 2017
      demonstrate rising proportions of female trainees and specialists. Female trainee
      and specialist numbers increased from 26 to 37% and from 13 to 22% respectively.
      Globally, female representation in leadership positions was presidencies of
      critical care organisations (0-41%), representation on critical care medicine
      boards and councils (8-50%) and faculty representation at symposia (7-34%).
      Significant gaps in knowledge exist: data from low and middle-income countries,
      the age distribution and the time taken to enter and complete training.
      CONCLUSIONS: Despite limited information globally, available data suggest that
      females are under-represented in training programmes, specialist positions,
      academic faculty and leadership roles in intensive care. There are significant
      gaps in data on female participation in the critical care workforce. Further data
      from intensive care organisations worldwide are required to understand the
      demographics, challenges and barriers to their professional progress.

PMID- 30196797
TI  - Estimation of the burden of flu-association influenza-like illness visits on
      total clinic visits through the sentinel influenza monitoring system in Senegal
      during the 2013-2015 influenza seasons.
AB  - Knowing the burden of influenza is helpful for policy decisions. Here we
      estimated the contribution of influenza-like illness (ILI) visits associated with
      laboratory-confirmed influenza among all clinic visits in a Senegal sentinel
      network. ILI data from ten sentinel sites were collected from January 2013 to
      December 2015. ILI was defined as an axillary measured fever of more than 37.5 
      degrees C with a cough or a sore throat. Collected nasopharyngeal swabs were
      tested for influenza viruses by rRT-PCR. Influenza-associated ILI was defined as
      ILI with laboratory-confirmed influenza. For the influenza disease burden
      estimation, we used all-case outpatient visits during the study period who sought
      care at selected sites. Of 4030 ILI outpatients tested, 1022 were influenza
      positive. The estimated proportional contribution of influenza-associated ILI
      was, per 100 outpatients, 1.2 (95% CI 1.1-1.3), 0.32 (95% CI 0.28-0.35), 1.11
      (95% CI 1.05-1.16) during 2013, 2014, 2015, respectively. The age-specific
      outpatient visits proportions of influenza-associated ILI were higher among
      children under 5 years (0.68%, 95% CI: 0.62-0.70). The predominant virus during
      years 2013 and 2015 was influenza B while A/H3N2 subtype was predominant during
      2014. Influenza viruses cause a substantial burden of outpatient visits
      particularly among children under 5 of age in Senegal and highlight the need of
      vaccination in risk groups.

PMID- 30196798
TI  - From insertion to removal: A multicenter survival analysis of an admitted cohort
      with peripheral intravenous catheters inserted in the emergency department.
AB  - BACKGROUND: Most patients admitted to the hospital via the emergency department
      (ED) do so with a peripheral intravenous catheter/cannula (PIVC). Many PIVCs
      develop postinsertion failure (PIF). OBJECTIVE: To determine the independent
      factors predicting PIF after PIVC insertion in the ED. METHODS: We analyzed data
      from a prospective clinical cohort study of ED-inserted PIVCs admitted to the
      hospital wards. Independent predictors of PIF were identified using Cox
      proportional hazards regression modeling. RESULTS: In 391 patients admitted from
      2 EDs, the rate of PIF was 31% (n=118). The types of PIF identified were
      infiltration, occlusion, pain and/or peripheral intravenous assessment score >2
      (ie, the hospital's assessment of PIVC phlebitis), and dislodgement (ie,
      accidental securement device failure or purposeful removal). Of the PIVCs that
      failed, infiltration and occlusion combined were the most common causes of PIF
      (n=55, 47%). The median PIVC dwell time was 28.5 hours (interquartile range
      [IQR], 17.4-50.8 hours). The following variables were associated with increased
      risk of PIF: being an older patient (for a 1-year increase, hazard ratio [HR],
      1.02; 95% confidence interval [CI], 1.01-1.03; P=.0001); having an Australian
      Triage Scale score of 1 or 2 compared to a score of 3, 4, or 5 (HR, 2.04; 95% CI,
      1.39-3.01; P=.0003); having an ultrasound-guided PIVC (HR, 6.52; 95% CI, 2.11
      20.1; P=.0011); having the PIVC inserted by a medical student (P=.0095);
      infection prevention breaches at insertion (P=.0326); and PIVC inserted in the
      ante cubital fossa or the back of hand compared to the upper arm (P=.0337).
      CONCLUSION: PIF remains at an unacceptable level in both traditionally inserted
      and ultrasound-inserted PIVCs.Clinical trial registrationAustralian and New
      Zealand Trials Registry (ANZCTRN12615000588594).

PMID- 30196799
TI  - The cost of managing complex surgical site infections following primary hip and
      knee arthroplasty: A population-based cohort study in Alberta, Canada.
AB  - OBJECTIVE: Nearly 800,000 primary hip and knee arthroplasty procedures are
      performed annually in North America. Approximately 1% of these are complicated by
      a complex surgical site infection (SSI), leading to very high healthcare costs.
      However, population-based studies to properly estimate the economic burden are
      lacking. We aimed to address this knowledge gap. DESIGN: Economic burden study.
      METHODS: Using administrative health and clinical databases, we created a cohort
      of all patients in Alberta, Canada, who received a primary hip or knee
      arthroplasty between April 1, 2012, and March 31, 2015. All patients who
      developed a complex SSI postoperatively were identified through a provincial
      infection prevention and control database. A combination of corporate
      microcosting data and gross costing methods were used to determine total mean 12-
      and 24-month costs, enabling comparison of costs between the infected and
      noninfected patients. RESULTS: Mean 12-month total costs were significantly
      greater in patients who developed a complex SSI compared to those who did not
      (CAD$95,321 [US$68,150] vs CAD$19,893 [US$14,223]; P < .001). The magnitude of
      the cost difference persisted even after controlling for underlying patient
      factors. The most commonly identified causative pathogen (38%) was Staphylococcus
      aureus (95% MSSA). CONCLUSIONS: Complex SSIs following hip and knee arthroplasty
      lead to high healthcare costs, which are expected to rise as the yearly number of
      surgeries increases. Using our costing estimates, the cost-effectiveness of
      different strategies to prevent SSIs should be investigated.

PMID- 30196800
TI  - Decoding Brain States for Planning Functional Grasps of Tools: A Functional
      Magnetic Resonance Imaging Multivoxel Pattern Analysis Study.
AB  - OBJECTIVES: We used multivoxel pattern analysis (MVPA) to investigate neural
      selectivity for grasp planning within the left-lateralized temporo-parieto
      frontal network of areas (praxis representation network, PRN) typically
      associated with tool-related actions, as studied with traditional neuroimaging
      contrasts. METHODS: We used data from 20 participants whose task was to plan
      functional grasps of tools, with either right or left hands. Region of interest
      and whole-brain searchlight analyses were performed to show task-related neural
      patterns. RESULTS: MVPA revealed significant contributions to functional grasp
      planning from the anterior intraparietal sulcus (aIPS) and its immediate
      vicinities, supplemented by inputs from posterior subdivisions of IPS, and the
      ventral lateral occipital complex (vLOC). Moreover, greater local selectivity was
      demonstrated in areas near the superior parieto-occipital cortex and dorsal
      premotor cortex, putatively forming the dorso-dorsal stream. CONCLUSIONS: A
      contribution from aIPS, consistent with its role in prospective grasp formation
      and/or encoding of relevant tool properties (e.g., potential graspable parts), is
      likely to accompany the retrieval of manipulation and/or mechanical knowledge
      subserved by the supramarginal gyrus for achieving action goals. An involvement
      of vLOC indicates that MVPA is particularly sensitive to coding of object
      properties, their identities and even functions, for a support of grip formation.
      Finally, the engagement of the superior parieto-frontal regions as revealed by
      MVPA is consistent with their selectivity for transient features of tools (i.e.,
      variable affordances) for anticipatory hand postures. These outcomes support the
      notion that, compared to traditional approaches, MVPA can reveal more fine
      grained patterns of neural activity. (JINS, 2018, 24, 1013-1025).

PMID- 30196801
TI  - Psychiatric symptoms and risk of victimisation: a population-based study from
      Southeast London.
AB  - : AimsAlthough violence is a vital public health problem, no prospective studies
      have tested for subsequent vulnerability to violence, as a victim or witness, in
      members of the general population with a range of psychiatric symptoms, or
      evaluated the importance of higher symptom burden on this vulnerability. METHODS:
      We used successive waves of a household survey of Southeast London, taken 2 years
      apart, to test if association exists between psychiatric symptoms (symptoms of
      psychosis, common mental disorders, post-traumatic stress disorder and
      personality disorder) and later victimisation, in the form of either witnessing
      violence or being physically victimised, in weighted logistic regression models.
      Statistical adjustment was made for prior violence exposure, sociodemographic
      confounders, substance/alcohol use and violence perpetration. Sensitivity
      analyses were stratified by violence perpetration, sex and history of mental
      health service use. RESULTS: After adjustments, psychiatric symptoms were
      prospectively associated with reporting any subsequent victimisation (odds ratio
      (OR) 1.88, 95% confidence interval (CI) 1.25-2.83), a two times greater odds of
      reporting witnessed violence (OR 2.24, 95% CI 1.33-3.76) and reporting physical
      victimisation (OR 1.76, 95% CI 1.01-3.06). One more symptom endorsed was
      accompanied by 47% greater odds of subsequent victimisation (OR 1.47, 95% CI 1.16
      1.86). In stratified analyses, statistical associations remained evident in non
      perpetrators, and among those without a history of using mental health services,
      and were similar in magnitude in both men and women. CONCLUSIONS: Psychiatric
      symptoms increase liability to victimisation compared with those without
      psychiatric symptoms, independently of a prior history of violence exposure and
      irrespective of whether they themselves are perpetrators of violence. Clinicians
      should be mindful of the impact of psychiatric symptoms on vulnerability to
      victimisation, including among those with common psychiatric symptoms and among
      those who are not considered at risk of perpetrating violence.

PMID- 30196802
TI  - Retrograde Personal Semantic Memory During Post-Traumatic Amnesia and Following
      Emergence.
AB  - OBJECTIVES: Anecdotal reports suggest that following traumatic brain injury (TBI)
      retrograde memories are initially impaired and recover in order of remoteness.
      However, there has been limited empirical research investigating whether a
      negative gradient in retrograde amnesia-relative preservation of remote over
      recent memory-exists during post-traumatic amnesia (PTA) compared with the acute
      phase post-emergence. This study used a repeated-measures design to examine the
      pattern of personal semantic (PS) memory performance during PTA and within two
      weeks of emergence to improve understanding of the nature of the memory deficit
      during PTA and its relationship with recovery. METHODS: Twenty patients with
      moderate-severe TBI and 20 healthy controls (HCs) were administered the Personal
      Semantic Schedule of the Autobiographical Memory Interview. The TBI group was
      assessed once during PTA and post-emergence. Analysis of variance was used to
      compare the gradient across lifetime periods during PTA relative to post
      emergence, and between groups. RESULTS: PS memory was significantly lower during
      PTA than post-emergence from PTA, with no relative preservation of remote
      memories. The TBI group was still impaired relative to HCs following emergence
      from PTA. Lower overall PS memory scores during PTA were associated with
      increased days to emerge from PTA post-interview. CONCLUSIONS: These results
      suggest a global impairment in PS memory across lifetime periods particularly
      during PTA, but still present within 2 weeks of emergence from PTA. PS memory
      performance may be sensitive to the diffuse nature of TBI and may, therefore,
      function as a clinically valuable indicator of the likely time to emerge from
      PTA. (JINS, 2018, 24, 1064-1072).

PMID- 30196803
TI  - Health justice partnerships: a promising model for increasing access to justice
      in health services.
AB  - Many people experience legal issues that affect their health, but do not seek
      legal help, particularly if they are disadvantaged in some way. This may be
      because they do not recognise they have a legal problem, they are unwilling or
      unable to address it, or they do not know how to go about dealing with it. Most
      people seek health care at some point, so linking health and legal services may
      help promote access to justice. There have been ongoing efforts in Australia to
      link health and law services, such as through co-locating health and legal
      services or through running legal 'clinics' in health services, but these have
      not always reached the intended clients. Fully integrated health justice
      partnerships are a model where the law/health partnership is collaborative at all
      levels of the organisation. This perspective piece argues that the model is
      particularly suitable for health services that have clients with needs in a
      specific area of law, and should be carefully targeted to where it is most
      needed. Factors that contribute to successful implementation of the model are
      described.

PMID- 30196804
TI  - Extracellular vesicles derived from donor oviduct fluid improved birth rates
      after embryo transfer in mice.
AB  - Embryo transfer (ET) is an important procedure for assisted reproduction.
      However, the relatively lower success rate of ET hampers its application
      potential. In this study we aimed to elucidate the effects of extracellular
      vesicles derived from donor oviduct fluid (EDOF) on embryo development after ET.
      Extracellular vesicles from the oviduct were isolated and purified using
      ultracentrifugation and identified using transmission electron microscopy,
      NanoSight, bicinchoninic acid (BCA) protein assay and western blotting. The
      results revealed that extracellular vesicles were present in donor oviduct fluid
      in higher concentrations (P < 0.05) and contained more proteins (P < 0.05) than
      extracellular vesicles derived from recipient oviduct fluid (EROF). EDOF or EROF
      were supplemented in an ET medium (ETM) and the results showed that EDOF
      significantly improved birth rate via resisting apoptosis and promoting
      differentiation. In conclusion, our study indicated that there are differences in
      EDOF and EROF and that supplementing EDOF to ETM can improve the efficiency of
      ET; improved ET efficiency promotes the use of gene editing and benefits assisted
      reproductive technology and animal welfare.

PMID- 30196805
TI  - Zebularine significantly improves the preimplantation development of ovine
      somatic cell nuclear transfer embryos.
AB  - Aberrant DNA methylation reduces the developmental competence of mammalian
      somatic cell nuclear transfer (SCNT) embryos. Thus, hypomethylation-associated
      drugs are beneficial for improving reprogramming efficiency. Therefore, in the
      present study we investigated the effect of zebularine, a relatively novel DNA
      methyltransferase inhibitor, on the developmental potential of ovine SCNT
      embryos. First, reduced overall DNA methylation patterns and gene-specific DNA
      methylation levels at the promoter regions of pluripotency genes (octamer-binding
      transcription factor 4 (Oct4), SRY (sex determining region Y)-box 2 (Sox2) and
      Nanog) were found in zebularine-treated cumulus cells. In addition, the DNA
      methylation levels in SCNT embryos derived from zebularine-treated cumulus cells
      were significantly reduced at the 2-, 4-, 8-cell, and blastocyst stages compared
      with their corresponding controls (P < 0.05). The blastocyst rate was
      significantly improved in SCNT embryos reconstructed by the cumulus donor cells
      treated with 5 nM zebularine for 12 h compared with the control group (25.4+/-1.6
      vs 11.8+/-1.7%, P < 0.05). Moreover, the abundance of Oct4 and Sox2 mRNA was
      significantly increased during the preimplantation stages after zebularine
      treatment (P < 0.05). In conclusion, the results indicate that, in an ovine
      model, zebularine decreases overall DNA methylation levels in donor cumulus cells
      and reconstructed embryos, downregulates the DNA methylation profile in the
      promoter region of pluripotency genes in donor cells and ultimately elevates the
      expression of pluripotency genes in the reconstructed embryos, which can lead to
      improved development of SCNT embryos.

PMID- 30196806
TI  - Fostering healthcare innovation in public hospitals: the Queensland experience.
AB  - Faced with scarce resources and a demand for health care that exceeds supply,
      health policy makers at all levels of government need to adopt some form of
      rationing when deciding which health services should be funded in the public
      health system. With a relatively small investment, programs such as Queensland
      Health's New Technology Funding Evaluation Program (NTFEP) fosters innovation by
      providing funding and pilot studies for new and innovative healthcare
      technologies. The NTFEP assists policy makers to make informed decisions
      regarding investments in new safe and effective technologies based on available
      evidence gathered from real-world settings relevant to Queensland patients and
      clinicians. In addition, the NTFEP allows appropriate patient access, especially
      in rural and remote locations, to potentially beneficial technologies and acts a
      gatekeeper, protecting them from technologies that may be detrimental or
      harmful.What is known about the topic? Jurisdictions have struggled to identify
      ways to manage the introduction of new and innovative health technologies into
      clinical practice. The 2009 review of health technology in Australia recommended
      better assessment and appraisal by ensuring real-life practices in hospitals and
      community settings were considered, with a consumer and patient focus.What does
      this paper add? Queensland Health's NTFEP provides a robust and transparent
      mechanism to manage the introduction of innovative healthcare technologies into
      clinical practice, providing an opportunity to collect real-world data outside of
      formal clinical trials. These data can not only be used to inform clinical, but
      also purchasing, decision-making within the public health system. This model of
      investment and innovation has the potential to be implemented in other
      jurisdictions and provide opportunities to share learnings.What are the
      implications for practitioners? Programs such as the NTFEP provide reassurance to
      practitioners and patients alike that innovative healthcare technologies are
      adopted in public hospitals using an evidence-based approach after demonstrating
      that they are not only safe and clinically effective, but represent value for
      money and improved patient outcomes in a public health system.

PMID- 30196807
TI  - Facilitating Colostrum Collection by Hospitalized Women in the Early Postpartum
      Period for Infant Trophic Feeding and Oral Immune Therapy.
AB  - Administration of colostrum for early trophic feedings and colostrum oral immune
      therapy for neonates in the NICU is essential to enhance gut maturation and lower
      risk of infections. However, it is often difficult for women to collect early
      colostrum because of its thick viscosity and low volume. Women may be unable to
      sit upright during pumping sessions because of postsurgical pain, acute or
      chronic illness, or birth complications and may need assistance. In this article,
      we describe specific techniques that providers can use to help women to collect
      colostrum when they are unable to accomplish collection on their own. Helping
      women collect and administer colostrum to their neonates in the NICU may engage
      and motivate them to continue to pump and provide breast milk for their
      hospitalized neonates.

PMID- 30196808
TI  - Risk-Appropriate Care to Improve Practice and Birth Outcomes.
AB  - Identification and referral of women with high-risk pregnancies to hospitals
      better equipped and staffed to provide care for them have been important steps to
      improve birth outcomes. Based on recent recommendations from the American College
      of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine to
      provide regionalized maternal care for pregnant women at high risk and reduce
      rates of maternal morbidity and mortality, health care organizations and
      providers have refocused their attention to women's well-being rather than solely
      on the well-being of the fetus or newborn. Opportunities to improve practice and
      birth outcomes exist through the implementation of a more standardized and
      integrated system of risk-appropriate care.

PMID- 30196809
TI  - The production of pig preimplantation embryos in vitro: Current progress and
      future prospects.
AB  - Human assisted reproductive technology procedures are routinely performed in
      clinics globally, and some of these approaches are now common in other mammals
      such as cattle. This is currently not the case in pigs. Given that the global
      population is expected to increase by over two billion people between now and
      2050, the demand for meat will also undoubtedly increase. With this in mind, a
      more sustainable way to produce livestock; increasing productivity and
      implementing methods that will lead to faster genetic selection, is imperative.
      The establishment of routine and production scale pig embryo in vitro production
      could be a solution to this problem. Producers would be able to increase the
      overall number of offspring born, animal transportation would be more
      straightforward and in vitro produced embryos could be produced from the gametes
      of selected elite. Here we review the most recent developments in pig embryology,
      outline the current barriers and key challenges that exist, and outline research
      priorities to surmount these difficulties.

PMID- 30196810
TI  - Follistatin supplementation during in vitro embryo culture improves developmental
      competence of bovine embryos produced using sex-sorted semen.
AB  - Using sex-sorted semen to produce offspring of desired sex is associated with
      reduced developmental competence in vitro and lower fertility rates in vivo. The
      objectives of the present study were to investigate the effects of exogenous
      follistatin supplementation on the developmental competence of bovine embryos
      produced with sex-sorted semen and possible link between TGF-beta regulated
      pathways and embryotrophic actions of follistatin. Effects of follistatin on
      expression of cell lineage markers (CDX2 and Nanog) and downstream targets of
      SMAD signaling (CTGF, ID1, ID2 and ID3) and AKT phosphorylation were
      investigated. Follistatin was supplemented during the initial 72 h of embryo
      culture. Exogenous follistatin restored the in vitro developmental competence of
      embryos produced with sex-sorted semen to the levels of control embryos produced
      with unsorted semen, and comparable results were obtained using sorted semen from
      three different bulls. The mRNA abundance for SMAD signaling downstream target
      genes, CTGF (SMAD 2/3 pathway) and ID2 (SMAD 1/5 pathway), was lower in
      blastocysts produced using sex-sorted versus unsorted semen, but mRNA levels for
      CDX2, NANOG, ID1 and ID3 were similar in both groups. Follistatin supplementation
      restored CTGF and ID2 mRNA in blastocysts produced using sex-sorted semen to
      levels of control embryos. Moreover, levels of phosphorylated (p)AKT (Ser-473 and
      Thr-308) were similar in embryos derived from sex-sorted and unsorted semen, but
      follistatin treatment increased pAKT levels in both groups. Taken together,
      results demonstrated that follistatin improves in vitro development of embryos
      produced with sex-sorted semen and such effects are associated with enhanced
      indices of SMAD signaling.

PMID- 30196811
TI  - Free Energy Landscape for the Entire Transport Cycle of Triose
      Phosphate/Phosphate Translocator.
AB  - Secondary active transporters translocate their substrates using the
      electrochemical potentials of other chemicals and undergo large-scale
      conformational changes. Despite extensive structural studies, the atomic details
      of the transport mechanism still remain elusive. We performed a series of all
      atom molecular dynamics simulations of the triose-phosphate/phosphate
      translocator (TPT), which exports organic phosphates in the chloroplast stroma in
      strict counter exchange with inorganic phosphate (Pi). Biased sampling methods,
      including the string method and umbrella sampling, successfully reproduced the
      conformational changes between the inward- and outward-facing states, along with
      the substrate binding. The free energy landscape of this entire TPT transition
      pathway demonstrated the alternating access and substrate translocation
      mechanisms, which revealed that Pi is relayed by positively charged residues
      along the transition pathway. Furthermore, the conserved Glu207 functions as a
      "molecular switch", linking the local substrate binding and the global
      conformational transition. Our results provide atomic-detailed insights into the
      substrate transport mechanism of the antiporter.

PMID- 30196812
TI  - Corrigendum to "SurR9C84A protects and recovers human cardiomyocytes from hypoxia
      induced apoptosis" [Exp. Cell Res. 350(1) (2017) 19-31].

PMID- 30196813
TI  - Microbial electrocatalysis: Redox mediators responsible for extracellular
      electron transfer.
AB  - Redox mediator plays an important role in extracellular electron transfer (EET)
      in many environments wherein microbial electrocatalysis occurs actively. Because
      of the block of cell envelope and the low difference of redox potential between
      the intracellular and extracellular surroundings, the proceeding of EET depends
      mainly on the help of a variety of mediators that function as an electron carrier
      or bridge. In this Review, we will summarize a wide range of redox mediators and
      further discuss their functional mechanisms in EET that drives a series of
      microbial electrocatalytic reactions. Studying these mediators adds to our
      knowledge of how charge transport and electrochemical reactions occur at the
      microorganism-electrode interface. This understanding would promote the
      widespread applications of microbial electrocatalysis in microbial fuel cells,
      bioremediation, bioelectrosynthesis, biomining, nanomaterial productions, etc.
      These improved applications will greatly benefit the sustainable development of
      the environmental-friendly biochemical industries.

PMID- 30196814
TI  - Editor's Choice - Cerebral Hyperperfusion Syndrome After Carotid Artery Stenting:
      A Systematic Review and Meta-analysis.
AB  - INTRODUCTION: Cerebral hyperperfusion syndrome (CHS) is a preventable cause of
      stroke after carotid endarterectomy (CEA). There are currently no pooled data
      available on the incidence of CHS after carotid artery stenting (CAS). The aim of
      this review was to assess the relevance of CHS in the procedural stroke rate
      following CAS. METHOD: A systematic search on incidence rates of CHS after CAS
      was conducted in the MEDLINE, EMBASE, and Cochrane databases in November 2017. A
      meta-regression analysis was performed on CHS to explain heterogeneity and
      determine the impact of potential risk factors on observed CHS. The
      methodological quality of the included studies was assessed using the Cowley
      criteria. RESULTS: The pooled CHS risk across 33 studies concerning 8731 CAS
      patients was 4.6% (3.1-6.8%). Stroke occurred in 47% of CHS patients, of which
      54% were fatal or disabling. Average time from procedure to symptoms was 12 h
      (IQR 8-36 h). Impaired cerebrovascular reserve (CVR) was associated with a higher
      risk of CHS after CAS (RR 5.18; 95% CI 1.0-26.8; p = .049). Symptomatic status
      was associated with a lower risk of CHS (RR 0.20; 95% CI 0.07-0.59; p = .001).
      CONCLUSION: CHS is a serious and frequent complication in patients undergoing
      carotid angioplasty with stenting, and is most likely to occur in the very early
      post-procedural period. Future studies are encouraged to investigate the effect
      of intensive haemodynamic monitoring, including blood pressure control and
      assessment of cerebral blood flow, on the incidence of stroke caused by CHS after
      CAS.

PMID- 30196815
TI  - In Situ Antegrade Laser Fenestrations During Endovascular Aortic Repair.
AB  - INTRODUCTION: The technique and preliminary outcomes are reported for laser
      fenestrated endografting (LfEVAR), developed as an alternative procedure for
      endovascular repair of thoraco-abdominal aortic aneurysms (TAAAs), type IA
      endoleaks (T1AELs), and pararenal aortic aneurysms (PAAAs). METHODS: Patients
      with TAAA, T1AEL, and PAAA considered unfit for open repair by a
      multidisciplinary team and who could not benefit from a custom made device were
      selected. LfEVAR is a physician modified technique requiring sequential steps.
      After preliminary stenting of each target artery, a standard stent graft was
      deployed in the aorta. Laser fenestration was performed using a steerable sheath
      positioned in the stent graft lumen in front of each target artery ostium. After
      progressive dilation of the laser fenestration, bridging stents were placed and
      flared to insure accurate perfusion of the visceral arteries. RESULTS: Between
      August 2015 and March 2017, 16 consecutive patients were treated using LfEVAR
      including two TAAAs, four T1AELs, and 10 PAAAs. Thirty-three laser fenestrations
      were performed with a 94.3% success rate for visceral artery fenestration. The
      median ischaemic was 7.5 minutes for the superior mesenteric artery, 48 and 50
      minutes for the left and right renal arteries, and 125 minutes for the coeliac
      trunk. Four secondary procedures were required: two endoleaks (type II and III),
      and two related to fenestrations: one renal stent dislocation, and one renal
      artery stent stenosis. During a mean follow up of 17 months, no deaths occurred.
      Follow up computed tomography (CT) scans performed at 30 days, 6, 12, and 18
      months were satisfactory (4 endoleaks and two aneurysm enlargements were
      observed). The follow up CT scan imaging demonstrated 97% primary patency.
      CONCLUSION: In situ antegrade LfEVAR is feasible and a safe alternative option
      for high risk inoperable patients or for those not eligible for custom made
      device endografting, particularly in emergency cases.

PMID- 30196816
TI  - Effect of Arrival of Prior Mammograms on Recall Negation for Screening Mammograms
      Performed With Digital Breast Tomosynthesis in a Clinical Setting.
AB  - PURPOSE: This retrospective study evaluates the effect of comparison with prior
      mammograms on recall negation for screening mammography performed with digital
      breast tomosynthesis (DBT) in a clinical setting and compares it with that
      performed without DBT. METHODS: This is an Institutional Review Board-approved,
      HIPAA-compliant retrospective review of the electronic medical record for all
      nonbaseline screening mammograms performed in clinical practice over 13 months.
      For each mammogram, we recorded if DBT were used, the BI-RADS assigned at initial
      interpretation, and whether prior mammograms were available at initial
      interpretation. If prior mammograms arrived later for comparison, the final BI
      RADS assigned after comparison was recorded. A mammogram assigned a BI-RADS 0 at
      initial interpretation and assigned a BI-RADS 1 or BI-RADS 2 after prior
      mammograms arrived for comparison was labeled as a recall that was negated by the
      arrival of prior mammograms. The number of recalls negated for mammograms that
      used DBT was compared with that for mammograms that did not use DBT. RESULTS:
      Arrival of prior mammograms for comparison negated the need for recall for
      mammograms performed with DBT by 67.67% and negated the need for recall for
      mammograms performed without DBT by 55.80%. After adjusting for age, density, and
      time between mammograms, the percentage of recalls negated by comparison with
      prior mammograms was not significantly different for mammograms performed with
      DBT than it was for those performed without DBT. CONCLUSION: Comparison with
      prior mammograms remains important for the minimization of recall rates during
      the use of DBT for screening mammography in the clinical setting.

PMID- 30196817
TI  - Patient-Friendly Summary of the ACR Appropriateness Criteria: Imaging for
      Transcatheter Aortic Valve Replacement.

PMID- 30196818
TI  - 86-Year-Old Man With Sharp Chest Pain and Dyspnea.

PMID- 30196819
TI  - 58-Year-Old Man With Eosinophilia, Lymphadenopathy, and Proteinuria.

PMID- 30196820
TI  - Granulocyte-macrophage colony-stimulating factor as a mediator of autoimmunity in
      multiple sclerosis.
AB  - Autoreactive, myelin-specific, CD4+ T cells have a central role in multiple
      sclerosis (MS) pathogenesis; however the exact phenotype characteristics of these
      cells remain elusive. Recently, granulocyte-macrophage colony-stimulating factor
      (GM-CSF) expression has emerged as the main pathological signature of the
      encephalogenicity in both T and B cell compartment. In this review we have
      summarized the current data supporting GM-CSF relevance in MS pathophysiology, in
      the context of both immunomodulatory and neuroinflammatory processes; as well as
      the potential cellular sources of this stimulating factor, including different T
      and B cell subsets.

PMID- 30196821
TI  - Neuroinflammatory responses in experimental and human stroke lesions.
AB  - Neuroinflammation has been suggested as an attractive treatment target in stroke,
      since it offers a broader therapeutic window in comparison to currently
      established thrombolytic approaches. Inflammatory cells of both the innate and
      the adaptive immune system have been identified in experimental as well as human
      stroke lesions. In animal models, various therapeutic strategies targeting
      neuroinflammation have shown beneficial effects, however, translation to human
      disease has so far been disappointing. Comparisons of the numerous experimental
      findings with until now rather limited human data reveal that despite
      similarities in the core signature of the inflammatory reaction, human stroke
      lacks clearly definable temporal and spatial sequences of lesion maturation that
      can be generalized and applied for a large patient population. Thus, in
      comparison with well-timed animal models with a clear succession of pathogenic
      mechanisms, precise and stage-dependent targeting of neuroinflammation in human
      stroke patients will be difficult to achieve. In addition, the contribution of
      different components of the innate and adaptive immune system quantitatively
      varies between humans and experimental animals and even between different modes
      of ischemia induction in animal models. Finally, human stroke lesions develop on
      a basis of age-dependent microglia pre-activation, which may have major impact on
      the further activation and functional differentiation of these cells. Knowledge
      about neuroinflammation in stroke patients, however, is currently limited and it
      has to be determined in future studies to what extent different causes of stroke
      and different co-morbidities in the patients result in distinct patterns of
      inflammation.

PMID- 30196822
TI  - CTLA-4, PD-1 and TIM-3 expression predominantly downregulated in MS patients.
AB  - Multiple sclerosis (MS), is an autoimmune disorder of central nervous system
      (CNS) characterized by inflammation and demyelination. Self-tolerance impairment
      is considered to be induced by a combination of inherited susceptibility and
      environmental agents. In this work, we demonstrate that a reduction in the
      comparative expression of well-known inhibitory receptors (i.e., CTLA-4, PD-1,
      and TIM-3) is importantly linked with MS patients compared to healthy controls.
      The relative expression of interested genes was performed on peripheral blood
      mononuclear cells (PBMCs), by using quantitative real time-PCR (qRT-PCR). Our
      data highlighted the role of inhibitory receptors in the maintenance of immune
      homeostasis in autoimmune disease.

PMID- 30196823
TI  - Genome-wide association study in Guillain-Barre syndrome.
AB  - Guillain-Barre syndrome (GBS) is considered to have an immune-mediated basis, but
      the genetic contribution to GBS is unclear. We conducted a GWAS involving 215 GBS
      patients and 1,105 healthy controls. No significant associations of individual
      SNPs or imputed HLA types were observed. We performed a genome-wide complex trait
      analysis for evaluation of the heritability of GBS, and found that common SNPs
      contribute up to 25% of susceptibility to the disease. Genetic risk score
      analysis showed no evidence of overlap in genetic susceptibility factors of GBS
      and multiple sclerosis. Given the unexplained heritability of the trait further
      larger GWAS are indicated.

PMID- 30196824
TI  - Fulminant Anti-GAD antibody encephalitis presenting with status epilepticus
      requiring aggressive immunosuppression.
AB  - Antibodies against glutamic acid decarboxylase (GAD) are reported in association
      with numerous neurological conditions including temporal lobe epilepsy and limbic
      encephalitis. We report a case of Anti-GAD-Antibody associated encephalitis
      presenting with epilepsia partialis continua (EPC) progressing to a fulminant
      encephalopathy preferentially affecting the frontal lobes associated with coma
      and refractory status epilepticus. The abnormalities identified on MRI included
      marked bilateral frontal lobe involvement which has not been reported in other
      auto-immune encephalitides and may be specific for Anti-GAD-Antibody associated
      encephalitis. Similar to the majority of cases of Anti-GAD associated
      neurological disturbance no underlying malignancy was identified. Treatment with
      high dose corticosteriods, IVIG and plasmapheresis had minimal response, but
      escalation of treatment with rituximab and cyclophosphamide was associated with
      clinical improvement, reducing antibody titers and resolution of MRI changes.

PMID- 30196825
TI  - Th17 pathway signatures in a large Indian cohort of Guillain Barre syndrome.
AB  - The etiopathogenesis of Guillain Barre Syndrome (GBS) is inadequately understood.
      The role of immuno-inflammatory Th17 pathway was examined in GBS patients by
      genetic, gene expression and biochemical studies. Genotyping of G197A single
      nucleotide polymorphism within IL17 gene was carried out by PCR-RFLP method in
      220 GBS patients. Quantification of gene expression of STAT3 and RORC and
      estimation of plasma level of IL-17A were carried out in a subset of patients.
      Significantly increased STAT3 gene expression in lymphocytes and plasma IL-17A
      levels were observed in GBS patients. This study adds new dimension and
      reinforces important implications of Th17 pathway in GBS.

PMID- 30196826
TI  - Oxymatrine attenuates cognitive deficits through SIRT1-mediated autophagy in
      ischemic stroke.
AB  - To investigate if oxymatrine could ameliorate hippocampus ischemia/reperfusion
      (I/R) injury induced in rats and explore the possible mechanism. Rats were
      randomly divided into four groups: sham group, I/R group, I/R + OMT-treated
      group, I/R + Vehicle-treated group. Oxymatrine or vehicle solution was
      intraperitoneally injected OMT (150 mg/kg) 60 min before renal ischemia
      respectively. Water maze was measured; cell apoptosis was assessed by doing TUNEL
      assay and detecting the expression of P53, Bax, and Cleaved-Caspase-3; autophagy
      were assessed by measuring the expression of LC3 and P62. The expression of SIRT1
      was also detected. Oxymatrine treatment alleviated histological injury in I/R
      rats, inhibiting apoptosis, promoting autophagy and accompanied by upregulated
      expression of SIRT1 proteins. Oxymatrine may attenuate hippocampus
      ischemia/reperfusion injury through upregulation SIRT1, further influencing the
      processes of apoptosis and autophagy.

PMID- 30196828
TI  - MicroRNA-150 targets PU.1 and regulates macrophage differentiation and function
      in experimental autoimmune encephalomyelitis.
AB  - PU.1 is a transcription factor which is expressed in myeloid cells. Herein, we
      investigated the expression of PU.1 and its potentially targeting miRNAs in the
      central nervous system (CNS) of mice with experimental autoimmune encephalitis
      (EAE) and in cultured primary macrophages. PU.1 levels where highly induced in
      EAE spinal cords and in activated macrophages; this was associated with a
      significant reduction in miR-150-5p levels at chronic phase of disease and in
      activated cells. Luciferase assays confirmed the PU.1-miR-150-5p interaction.
      Overexpression of miR-150-5p in macrophages decreased the expression of
      proinflammatory cytokines and shifted the polarization of macrophages away from
      the M1-like phenotype.

PMID- 30196827
TI  - Lower level noise exposure that produces only TTS modulates the immune
      homeostasis of cochlear macrophages.
AB  - Noise exposure producing temporary threshold shifts (TTS) has been demonstrated
      to cause permanent changes to cochlear physiology and hearing function. Several
      explanations have been purported to underlie these long-term changes in cochlear
      function, such as damage to sensory cell stereocilia and synaptic connections
      between sensory cells and their innervation by spiral ganglion neurons, and
      demyelination of the auditory nerve. Though these structural defects have been
      implicated in hearing difficulty, cochlear responses to this stress damage
      remains poorly understood. Here, we report the activation of the cochlear immune
      system following exposure to lower level noise (LLN) that causes only TTS. Using
      multiple morphological, molecular and functional parameters, we assessed the
      responses of macrophages, the primary immune cell population in the cochlea, to
      the LLN exposure. This study reveals that a LLN that causes only TTS increases
      the macrophage population in cochlear regions immediately adjacent to sensory
      cells and their innervations. Many of these cells acquire an activated morphology
      and express the immune molecules CCL2 and ICAM1 that are important for macrophage
      inflammatory activity and adhesion. However, LLN exposure reduces macrophage
      phagocytic ability. While the activated morphology of cochlear macrophages
      reverses, the complete recovery is not achieved 2 months after the LLN exposure.
      Taken together, these observations clearly implicate the cochlear immune system
      in the cochlear response to LLN that causes no permanent threshold change.

PMID- 30196829
TI  - Age-adjusted CSF beta2-microglobulin and lactate are increased and ACE is
      decreased in patients with multiple sclerosis, but only lactate correlates with
      clinical disease duration and severity.
AB  - We compared cerebrospinal fluid levels of lactate, beta2-microglobulin and
      angiotensin-converting enzyme (ACE) between 438 untreated patients with multiple
      sclerosis and 276 patients with non-inflammatory neurological disorders. Age
      adjusted beta2-microglobulin and lactate were significantly higher and ACE was
      significantly lower in MS patients than in controls. beta2-microglobulin and ACE
      positively correlated with high significance both in MS patients and controls.
      While disease duration negatively correlated and progression index, defined as
      EDSS score divided by disease duration in years, positively correlated with age
      adjusted lactate levels, both did neither correlate with beta2-microglobulin nor
      with ACE. Both CSF beta2-microglobulin and ACE deserve further investigation as
      biomarkers of multiple sclerosis pathophysiology.

PMID- 30196830
TI  - Differential binding patterns of anti-sulfatide antibodies to glial membranes.
AB  - Sulfatide is a major glycosphingolipid in myelin and a target for autoantibodies
      in autoimmune neuropathies. However neuropathy disease models have not been
      widely established, in part because currently available monoclonal antibodies to
      sulfatide may not represent the diversity of anti-sulfatide antibody binding
      patterns found in neuropathy patients. We sought to address this issue by
      generating and characterising a panel of new anti-sulfatide monoclonal
      antibodies. These antibodies have sulfatide reactivity distinct from existing
      antibodies in assays and in binding to peripheral nerve tissues and can be used
      to provide insights into the pathophysiological roles of anti-sulfatide
      antibodies in demyelinating neuropathies.

PMID- 30196831
TI  - Increased costimulatory molecule expression of thymic and peripheral B cells and
      a sensitivity to IL-21 in myasthenia gravis.
AB  - B cells may contribute to the pathogenesis of myasthenia gravis with anti
      acetylcholine antibodies (AChR+ MG) by co-stimulation or selection of T cells. In
      this study, we investigated costimulatory molecules on B cells in the blood and
      in the thymus as well as by TLR9 and IL-21 stimulations in AChR+ MG patients with
      or without immunosuppressive treatment and controls. CD80 and CD86 expression on
      B cells was increased in the peripheral blood and in the thymus of untreated
      patients. CD86 was further amplified by IL-21. A role for activated B cells,
      active thymic environment and IL-21 is implicated in MG.

PMID- 30196832
TI  - Effect of fingolimod action on the release of monocyte-derived microvesicles in
      multiple sclerosis patients.
AB  - Recently, microvesicles (MVs) were considered as important mediators of
      intercellular communication, especially in pathological conditions as Multiple
      Sclerosis (MS). In myeloid cells, MV shedding is induced by the receptor P2X7
      with the involvement of acid sphingomyelinase (A-SMase) and release of the IL
      1beta. In this study we evaluate how Fingolimod affects MVs production by the
      monocytes, as well as P2X7R, IL-1beta expression and A-SMase activity. Treatment
      decreased MVs production and IL-1beta expression. This effect was associated with
      the inhibition of A-SMase activity in BzATP-stimulated monocytes from MS
      patients. These evidences suggest monocyte MVs as a possible disease and drug
      efficacy biomarkers.

PMID- 30196833
TI  - High levels of antibodies against PtpA and PknG secreted by Mycobacterium avium
      ssp. paratuberculosis are present in neuromyelitis optica spectrum disorder and
      multiple sclerosis patients.
AB  - Mycobacterium avium ssp. paratuberculosis (Map) is the etiological agent of
      Paratuberculosis in ruminants. Protein tyrosine phosphatase A (PtpA) and protein
      kinase G (PknG) are secreted proteins necessary for the survival of the pathogen
      within macrophages. In this study we analyzed if Map was able to grow within
      astrocytes and investigated on the presence of antibodies against PtpA and PknG
      proteins in MS and NMOSD patients by ELISA. Map was unable to proliferate in
      astrocytes after of 72 h post-infection, but we observed a high level of
      antibodies against both virulence factors, suggesting that these patients have
      been exposed/infected with Map.

PMID- 30196834
TI  - PDCB does not promote CNS autoimmunity in the context of genetic susceptibility
      but worsens its outcome.
AB  - BACKGROUND: Para-dichlorobenzene (PDCB) is an aromatic hydrocarbon contained in
      mothballs that is potentially neurotoxic. A potential pathogenic role of PDCB in
      MS pathogenesis has been suggested. METHODS: To determine the ability of chronic
      PDCB ingestion to induce CNS autoimmunity in a genetically susceptible mammalian
      species, naive myelin oligodendrocyte glycoprotein peptide (MOGp)35-55 T cell
      receptor (TCR) transgenic mice (2D2) on the C57Bl/6 background were orally
      gavaged once daily with corn oil control, 125 mg/kg PDCB, or 250 mg/kg PDCB for
      45 days. The incidence of spontaneous EAE is increased in this mouse strain.
      RESULTS: Both PDCB treatment groups showed the same spontaneous incidence of EAE,
      an earlier disease onset, and a slight decrease in survival for 125 mg/kg PDCB
      mice compared to control mice. We were unable to detect any PDCB, or its
      metabolites 2,5-dichlorophenol, 2,5-dicholormethylsulfide, and 2,5
      dichloromethylsulfone in the brain and spinal cord of control mice. In contrast,
      PDCB was readily detectable in both compartments in mice who received PDCB via
      oral gavage, with concentrations being significantly higher in the brain (p <
      0.01). Levels of the metabolites 2,5-dichlorophenol and 2,5-dichloromethylsulfone
      were also significantly higher in brains compared to spinal cords. CONCLUSION:
      Our study refutes the hypothesis that PDCB or its metabolites trigger spontaneous
      T cell-mediated CNS autoimmunity in the setting of genetic susceptibility. A
      slight increase in mortality with PDCB exposure may be due systemic toxicity of
      hydrocarbons.

PMID- 30196835
TI  - Increased serum microRNA-29b expression and bad recovery in Japanese encephalitis
      virus infected patients; A new component to improve the disease recovery.
AB  - BACKGROUND: Japanese encephalitis virus (JEV) is a neurotropic mosquito-borne
      Flavivirus, mainly prevalent in Asia. It is the most important causative agent of
      acute viral encephalitis in humans. Recently, micro RNAs are discovered as a key
      regulator of inflammatory and immune responses in various diseases including
      neurological and viral infections. Thus, this study was proposed to check whether
      changes in cellular miRNA expression due to JE virus infection, can be detected
      in circulation which would be helpful in diagnosis and treatment. METHODS: miRNAs
      (miR-29b and miR-146a) were analyzed in the serum of JEV infected patients using
      quantitative reverse transcription polymerase chain reaction (RT-qPCR). RESULTS:
      miR-146a was found significantly decreased (p = 0.0008) in JEV infected patients
      as compared to healthy controls whereas miR-29b was significantly increased (p =
      0.001) in JEV patients recovered with neurological sequelae when compared to
      those recovered without sequelae. CONCLUSION: In conclusion, miRNA can be
      measured in serum. Studying microRNAs will provide novel information and help us
      to identify the components that can serve as biomarkers and can lead to new
      discovery in controlling disease recovery.

PMID- 30196836
TI  - Predictors of neural-specific autoantibodies and immunotherapy response in
      patients with cognitive dysfunction.
AB  - Recognition of autoimmunity as a cause of encephalopathy has increased. Recent
      studies have validated the use of Antibody-Prevalence-in-Epilepsy (APE) and
      Responsive-to-immunotherapy-in-Epilepsy (RITE) scores in the evaluation and
      management of autoimmune-epilepsy. We aim to assess the utility of these models
      for patients with cognitive dysfunction. Among the evaluated patients, 17% had
      antibodies universally associated with autoimmune-encephalopathy. NMDA-R-IgG and
      LGI1-IgG were the most common antibody specificities. Antibody-Prevalence-in
      Epilepsy-and-Encephalopathy (APE2) score >= 4 was 99% sensitive and 93% specific
      for neural-specific-antibodies. Responsive-to-immunotherapy-in-Epilepsy-and
      Encephalopathy (RITE2) score >= 7 had 96% sensitivity and 86% specificity for
      favorable initial immunotherapy response. Application of these models may
      optimize autoantibody evaluations and immunotherapeutic trials.

PMID- 30196837
TI  - Serum levels of leptin and adiponectin are not associated with disease activity
      or treatment response in multiple sclerosis.
AB  - Adipokines secreted by fatty tissue have inflammatory properties and are
      suggested biomarkers of MS disease activity. To assess this, 88 MS patients were
      followed with nine repeated measurements of leptin and adiponectin and 12
      magnetic resonance imaging (MRI) scans for two years; six months without any
      immunomodulatory treatment followed by 18 months during interferon-beta (IFNB)
      treatment. Serum levels of leptin dropped and adiponectin increased upon
      initiation of IFNB-therapy, but were not associated with clinical or MRI disease
      activity or with treatment response. Our findings indicate that leptin and
      adiponectin are not useful as biomarkers of MS disease activity.

PMID- 30196838
TI  - Anti-inflammatory properties of Honokiol in activated primary microglia and
      astrocytes.
AB  - Honokiol has been used in traditional medicine for the treatment of inflammatory
      diseases. Activation of glial cells plays an essential role in neurodegenerative
      disorders. In this study, we show that Honokiol reduces the inflammatory response
      to LPS of primary cultures of microglia and astrocytes through the inhibition of
      pro-inflammatory mediators (iNOS, IL-6, IL-1beta and TNF-alpha) and the
      simultaneous stimulation of anti-inflammatory cytokines (IL-10). Expression of
      KLF4 was induced in microglia and astrocytes after treatment with LPS and this
      response was mitigated by Honokiol. These findings extend our understanding of
      the anti-inflammatory properties of Honokiol on central glial cells and support
      its use as a therapeutic compound in neuroinflammatory disorders.

PMID- 30196839
TI  - Variability in PolyIC induced immune response: Implications for preclinical
      maternal immune activation models.
AB  - Maternal infection during pregnancy may increase the risk of offspring
      neurodevelopmental disorders. The preclinical Polyinosinic-polycytidylic acid
      (PolyIC) model has become one of the most widely used approaches in maternal
      immune activation (MIA) research. However, variability in molecular weight may
      impact the immune activating potential of PolyIC. Nulliparous rats injected with
      high molecular weight PolyIC exhibit pronounced cytokine response and sickness
      behavior that was not observed in rats injected low molecular weight PolyIC.
      Although an essential next step is to extend these studies to pregnant animals,
      the preliminary results suggest that PolyIC molecular weight is an important
      experimental design consideration.

PMID- 30196840
TI  - Calcitonin gene-related peptide decreases IL-1beta, IL-6 as well as Ym1, Arg1,
      CD163 expression in a brain tissue context-dependent manner while ameliorating
      experimental autoimmune encephalomyelitis.
AB  - Activation states of immune cells (among them, the so-called pro- or anti
      inflammatory states) influence the pathogenesis of multiple sclerosis (MS). The
      neuropeptide calcitonin gene-related peptide (CGRP) can exert a pro- or anti
      inflammatory role in a context-dependent manner. In mice CGRP was found to
      attenuate the development of experimental autoimmune encephalomyelitis (EAE, a
      common MS animal model). We analyzed CGRP effects on the expression of cytokines
      and markers of activation states, as well as its intracellular cascade, following
      intrathecal administration during EAE immunization. Real Time quantitative-PCR
      (RT-PCR) showed that IL-1beta and IL-6 (associated to a pro-inflammatory state in
      EAE), but also Ym1 (also known as Chil3), Arg1 and CD163 (associated to an anti
      inflammatory state in EAE) were decreased in the encephalon (devoid of
      cerebellum). In the cerebellum itself, IL-1beta and Ym1 were decreased. TNF-alpha
      (associated to a pro-inflammatory state in EAE), but also IL-10 (associated to
      another type of anti-inflammatory state) and BDNF were unchanged in these two
      regions. No changes were detected in the spinal cord. Additional tendencies
      toward a change (as revealed by RT-PCR) were again decreases: IL-10 in the
      encephalon and Arg1 in the spinal cord. CGRP decreased percentage of Ym1+/CD68+
      immunoreactive cells and cell density of infiltrates in the cervical spinal cord
      pia mater. Instead, Ym1 in the underlying parenchyma and at thoracic and lumbar
      levels, as well as Arg1, were unchanged. In cultured microglia the neuropeptide
      decreased Ym1, but not Arg1, immunoreactivity. Inducible NOS (iNOS) was unchanged
      in spinal cord microglia and astrocytes. The neuropeptide increased the
      activation of ERK1/2 in the astrocytes of the spinal cord and in culture, but did
      not influence the activation of ERK1/2 or p38 in the spinal cord microglia.
      Finally, in areas adjacent to infiltration sites CGRP-treated microglia showed a
      larger ramification radius. In conclusion, CGRP-induced EAE amelioration was
      associated to a concomitant, context-dependent decrease in the expression of
      markers belonging to both pro- or anti-inflammatory activation states of immune
      cells. It can be hypothesized that CGRP-induced EAE attenuation is obtained
      through a novel mechanism that promotes down-regulation of immune cell activation
      that facilitates the establishment of a beneficial environment in EAE provided
      possibly also by other factors.

PMID- 30196841
TI  - Evaluating the response to locoregional and systemic treatment for hepatocellular
      carcinoma.
AB  - Evaluating the response to different treatments is a decisive factor in the
      clinical management of patients with hepatocellular carcinoma because it can
      determine the efficacy of the treatment and because it can detect the recurrence
      of treated tumors or the appearance of new lesions that can be candidates for new
      treatments. When locoregional treatments that induce necrosis or molecular
      therapies are applied, the treated lesions usually change their behavior on
      imaging studies. It is important to point out that the size of the lesions does
      not usually decrease, at least initially, and some lesions can even appear to
      increase in size. For this reason, it is essential to know the mechanisms of
      action for each treatment applied and the spectrum of findings that these
      treatments can cause in the different imaging techniques used to assess the
      response.

PMID- 30196842
TI  - Seminal vesicle cyst: An isolated finding?

PMID- 30196844
TI  - A Population-based Study of Survival Impact of New Targeted and Immune-based
      Therapies for Metastatic or Unresectable Melanoma.
AB  - AIMS: New targeted drugs and immune therapies reported since 2010 for metastatic
      or unresectable melanoma (MM) have shown improved survival in randomised trials.
      We studied the uptake of these new drugs and their impact on population-based
      survival. MATERIALS AND METHODS: This was a retrospective, population-based
      cohort study of all patients treated for MM in Ontario 2007-2015. Provincial
      administrative sources covering the whole population identified palliative
      systemic therapy, radiotherapy and metastasis surgery. Temporal trends in
      utilisation and survival were investigated, as was survival of treatments
      predefined as 'new drugs' (BRAF or MEK inhibitors, anti-CTLA4 and anti-PD-1
      antibodies). RESULTS: We identified 2793 treated MM patients. First treatment was
      systemic therapy (46%), radiotherapy (41%) and metastasis surgery (14%). Systemic
      treatment increased from 53% of patients (2007) to 75% (2015). New drug
      treatments increased from <6% of known first-line regimens in 2007 to 82% in
      2015. One and 2 year overall survival was 28% and 15%, respectively, for all MM
      2007-2009, rising to 46% and 35% for 2014-2015 (adjusted hazard ratio 0.56, 95%
      confidence interval 0.49-0.63, P < 0.0001). Survival gains were observed
      primarily among those cases initially treated with systemic therapy, which became
      dominated by the use of new drugs over the study period (2 year overall survival
      16% 2007-2009 versus 44% 2014-2015; adjusted hazard ratio 0.46, 95% confidence
      interval 0.38-0.56, P < 0.0001). CONCLUSIONS: Utilisation of new targeted drugs
      and immune therapies for MM has increased considerably in routine practice 2007
      2015. Consistent with the results of clinical trials, adoption was associated
      with substantial increases in survival of patients in the general population.

PMID- 30196845
TI  - Contact X-ray Brachytherapy as an Adjunct to a Watch and Wait Approach is an
      Affordable Alternative to Standard Surgical Management of Rectal Cancer for
      Patients with a Partial Clinical Response to Chemoradiotherapy.
AB  - AIMS: Emerging evidence suggests that contact X-ray brachytherapy (CXB) may
      increase the clinical complete response rate and durability when administered
      after standard chemoradiotherapy in patients with rectal cancer. The addition of
      CXB in partial responders is therefore probably cost-effective. The affordability
      of widening access to CXB in the UK, however, has not been evaluated. MATERIALS
      AND METHODS: Decision analytical modelling with Monte Carlo simulation was used
      to evaluate long-term costs for the management of patients with rectal cancers
      who were given a CXB boost when a clinical complete response was not initially
      achieved following chemoradiotherapy in order to facilitate a watch and wait
      approach. A third-party payer (National Health Service) perspective was adopted,
      probabilistic sensitivity analysis was carried out and a scenario analysis was
      performed to investigate the effect of the number of referral centres and number
      of patients treated with CXB. RESULTS: We estimate that 818 (95% confidence
      interval 628-1021) patients per year are eligible for CXB as an adjunct to a
      watch and wait approach in England and Wales. As this management is less costly
      than surgical management for each individual patient, the more patients treated,
      the more affordable the technology. Even if as few as 125 patients are treated
      nationally in 15 centres, the cost of implementing this technology would be less
      than L4 million. If the average number of patients treated in each centre is 30,
      this technology would be cost saving within 5 years. CONCLUSIONS: The cost of CXB
      is not prohibitive according to the National Institute for Health and Care
      Excellence threshold for implementation of new technology and may even be cost
      saving within 5 years compared with standard surgical management, depending on
      the uptake of the technology and the number of referral centres.

PMID- 30196846
TI  - Site-specific Chemotherapy Based on Predicted Primary Site by Pathological
      Profile for Carcinoma of Unknown Primary Site.
AB  - AIMS: Although platinum-based combination chemotherapies are commonly used for
      unfavourable subsets of cancer of unknown primary (CUP), the prognosis remains
      poor. Several studies have suggested that gene expression profiling or
      immunohistochemistry was useful for the prediction of primary sites in CUP, and
      site-specific therapy based on predicted primary sites might improve overall
      outcomes. In Japan, to identify primary sites, immunohistochemical tests were
      commonly used for CUP in clinical practice. However, it is unclear whether site
      specific therapy based on predicted primary sites by pathological examination
      contributes survival benefit for unfavourable CUP subsets. PATIENTS AND METHODS:
      In this study, 122 patients with unfavourable subsets of CUP were retrospectively
      reviewed. Ninety patients assigned to cohort A after July 2012 had received
      chemotherapy according to predicted primary sites; 32 patients assigned to cohort
      B before June 2012 had received platinum-based empiric chemotherapy. RESULTS: In
      cohort A, 56 patients (62.2%) with predicted primary sites by pathological
      examination received site-specific therapy; 34 patients (37.8%) with
      unpredictable primary sites received platinum-based empiric chemotherapy, the
      same as cohort B. The median overall survival was 20.3 months in patients with
      predictable primary sites in cohort A and 10.7 months in those of cohort B, with
      a significant difference between these cohorts (P = 0.03, adjusted hazard ratio =
      0.57, 95% confidence interval 0.34-0.94). CONCLUSION: Site-specific therapy based
      on predicted primary sites by pathological examination could improve prognosis in
      patients with an unfavourable subset of CUP.

PMID- 30196847
TI  - Development of a pharmacy referral protocol to enhance interprofessional services
      in a university-affiliated dental medicine clinic.
AB  - OBJECTIVE: To discuss the process of developing pharmacy consult services within
      a university-affiliated dental clinic. Secondary objectives are to describe the
      frequency of pharmacy consults provided when comparing the initial to the
      modified protocol and interventions, over time. SETTING: A university-affiliated
      student-driven dental medicine clinic in the Midwest. PRACTICE DESCRIPTION: The
      dental clinic consists of third- and fourth-year dental students who provide
      dental services and are supervised by dental faculty. Pharmacy consults are
      prompted due to patient criteria met on the protocol, patient-specific factors,
      drug information, or other reasons. Pharmacists are present to provide consults
      directly with dental students or patients. PRACTICE INNOVATION: Since October
      2013, pharmacy services have been implemented into a dental clinic. A protocol is
      established to identify dental patients with high risk medications and medical
      conditions that may interfere with dental treatment. The initial protocol has
      been modified to include additional high-risk medications and conditions that the
      pharmacy team was being consulted for outside the protocol criteria. EVALUATION:
      A retrospective chart review was completed to evaluate the frequency of use of
      the original pharmacy protocol and the interventions provided. After the protocol
      was modified to include additional high-risk criteria, a second chart review was
      completed to assess changes in frequency of protocol use and interventions
      provided. RESULTS: Pharmacists undergo extensive self-learning to understand the
      dental-related concerns of the high-risk criteria as well as the dental workflow.
      The original pharmacy protocol accounted for 42.3% (n = 113) of the overall
      pharmacy consults (n = 267). After protocol modifications, utilization increased
      to 76.4% (n = 352, total n = 461). CONCLUSION: Pharmacists are successfully
      integrated into a dental medicine clinic to provide services to enhance dental
      patient care. The approximate 30% increase in the use of the pharmacy consult
      protocol demonstrated that the modified version was more effective.

PMID- 30196848
TI  - Comprehensive steroid profiling by liquid chromatography coupled to high
      resolution mass spectrometry.
AB  - A steroidomics workflow has been developed in the objective of monitoring a wide
      range (n >150) of steroids in urine. The proposed workflow relies on the
      optimization of an adequate SPE extraction step followed by an UHPLC-HRMS/MS
      simultaneous analysis of both free and conjugated forms of C18, C19 and C21
      steroid hormones. On the basis of 44 selected steroids, representative of main
      classes of steroids constituting the steroidome, the performances of the
      developed workflow were evaluated in terms of selectivity, repeatability (< 13%)
      and linearity (R2> 0.985 in the concentration range [0.01-10 ng/mL]). As
      metabolites identification and characterization constitute the bottleneck of such
      profiling approaches, a homemade database was created encompassing a large number
      of characterized free and conjugated steroids (n> 150) for putative steroid-like
      biomarkers identification purposes. The efficiency of the workflow in
      highlighting fine modifications within the urinary steroidome was assessed in the
      frame of an anabolic treatment involving an intra-muscular administration of
      boldenone undecylenate (2 mg/kg) to veals (n=6) and the investigation of
      potential steroid biomarkers. Besides monitoring known phase II metabolites of
      boldenone in the bovine specie, namely, boldenone glucuronide and sulfate, the
      applied strategy also permitted to observe, upon boldenone administration, a
      modified profile of epiboldenone glucuronide. Furthermore, 31 signals
      corresponding to non-identified steroid species could also be highlighted as
      impacted upon the exogenous steroid treatment. This study is the first to
      simultaneously investigate both free and conjugated C18, C19 and C21 steroid
      hormones in their native form using UHPLC-HRMS/MS and allowing their
      comprehensive profiling. This strategy was probed in-vivo.

PMID- 30196849
TI  - Corrigendum to ''Person-centered analysis of psychological traits to explain
      heterogeneity in patient-reported outcomes of coronary artery disease- the
      THORESCI study'' [Journal of Affective Disorders (2018) 15;236:14-22].

PMID- 30196850
TI  - Corrigendum to ''The role of affective temperaments assessed by the Temperament
      Evaluation of Memphis, Pisa and San Diego-Autoquestionnaire (TEMPS-A) in the
      relationship between morningness-eveningness and bipolarity'' [Journal of
      Affective Disorders 232 (2018) 83-88].

PMID- 30196851
TI  - Corrigendum to "KCa1.1 is potential marker for distinguishing Ah-type
      baroreceptor neurons in NTS and contributes to sex-specific presynaptic
      neurotransmission in baroreflex afferent pathway" [Neurosci. Lett. 604 (2015) 1
      6].

PMID- 30196852
TI  - Using registry data to improve quality of care.
AB  - Patient registries provide clinicians, patients and families with the ability to
      track important health outcomes at a population, cystic fibrosis (CF) center, and
      patient level. International quality improvement (QI) work driven by registries
      has been effective at improving the health and the care delivered to the
      individual patient. In this review, we examine the role CF registries have played
      in the QI process over the years and discuss the inherent strengths and
      limitations that exist when using registry data for this purpose.

PMID- 30196854
TI  - Maxillary stability following Le Fort I osteotomy using prebent plates and wire
      fixation in patients undergoing surgery for OSAS.
AB  - The purpose of this study was to analyze the stability of Le Fort I maxillary
      advancement in the vertical and horizontal directions using a combination of wire
      and rigid fixation in patients undergoing surgery to treat obstructive sleep
      apnea (OSA). Wire osteosynthesis can be performed quicker and at a reduced cost.
      The lateral cephalograms of 21 patients were evaluated preoperatively (T0),
      immediately postoperatively (T1), and at least 6 months postoperatively (T2).
      Four cephalometric points were used to measure movement in the horizontal and
      vertical directions. Mean values were determined, and data were statistically
      analyzed by ANOVA to determine differences between time points. Of the four
      points analyzed, the average maxillary advancement in the horizontal direction
      was 7.48 mm and the relapse was 0.56 mm with absence of statistically significant
      differences between the measurements taken (T1) and (T2). There was a 5%
      probability of error in the vertical movements at the points I and posterior
      nasal spine. The combination of two pre-bent plates in piriform aperture with
      osteosynthesis using surgical steel wires in the zygomatic buttress in patients
      undergoing maxillary surgery for OSA stabilized the large horizontal maxillary
      advancements and enhanced vertical stability in the first molar and A point
      regions.

PMID- 30196853
TI  - Retinal AAV8-RS1 Gene Therapy for X-Linked Retinoschisis: Initial Findings from a
      Phase I/IIa Trial by Intravitreal Delivery.
AB  - This study evaluated the safety and tolerability of ocular RS1 adeno-associated
      virus (AAV8-RS1) gene augmentation therapy to the retina of participants with X
      linked retinoschisis (XLRS). XLRS is a monogenic trait affecting only males,
      caused by mutations in the RS1 gene. Retinoschisin protein is secreted
      principally in the outer retina, and its absence results in retinal cavities,
      synaptic dysfunction, reduced visual acuity, and susceptibility to retinal
      detachment. This phase I/IIa single-center, prospective, open-label, three-dose
      escalation clinical trial administered vector to nine participants with
      pathogenic RS1 mutations. The eye of each participant with worse acuity (<=63
      letters; Snellen 20/63) received the AAV8-RS1 gene vector by intravitreal
      injection. Three participants were assigned to each of three dosage groups: 1e9
      vector genomes (vg)/eye, 1e10 vg/eye, and 1e11 vg/eye. The investigational
      product was generally well tolerated in all but one individual. Ocular events
      included dose-related inflammation that resolved with topical and oral
      corticosteroids. Systemic antibodies against AAV8 increased in a dose-related
      fashion, but no antibodies against RS1 were observed. Retinal cavities closed
      transiently in one participant. Additional doses and immunosuppressive regimens
      are being explored to pursue evidence of safety and efficacy (ClinicalTrials.gov:
      NCT02317887).

PMID- 30196855
TI  - Accuracy of soft tissue prediction in surgery-first treatment concept in
      orthognathic surgery: A prospective study.
AB  - PURPOSE: The purpose of this study was to provide a quantitative accuracy
      assessment of soft tissue predictions generated by a computer-aided maxillofacial
      planning system in patients undergoing orthognathic surgery following the
      "surgery-first" treatment. MATERIALS AND METHODS: For this study, we looked at 16
      patients with open bite dentofacial-dysmorphosis who underwent orthognathic
      surgery. Surgeries were planned using conventional sketches and the newly
      developed computer-assisted SOTIRIOS planning software (developed by the
      authors). Validation procedures were performed in the following steps: (1)
      Standardized registration of the pre- and postoperative CT volumes; (2) Automated
      adjustment of the bone-related preoperative planning to the actual postoperative
      bony displacement; (3) Simulation of soft tissue changes according to the
      definitive bony movements; and (4) Calculation of soft tissue differences between
      the predicted and the actual 6-month postoperative results by distance mapping.
      RESULTS: The program produced a clinically satisfactory 3D soft tissue
      prediction, with a mean error of 1.46 mm +/- 1.53 mm. The program was suitable
      for use in virtual surgical planning without technical assistance. CONCLUSION:
      This study shows that the program is quite accurate, enabling the surgeon to
      predict the outcome of the soft tissue. This has the potential to promote the
      routine application of the surgery-first approach in patients suffering from open
      bite.

PMID- 30196856
TI  - Three-dimensional volumetric analysis of condylar head and glenoid cavity after
      mandibular advancement.
AB  - The aim of this study was to assess condylar resorption, spatial change in
      glenoid cavity, and its risk factors after mandibular advancement by three
      dimensional volumetric analysis. Subjects consisted of 30 condyles of 15 patients
      diagnosed with mandibular retrognathism who underwent Le Fort I and bilateral
      sagittal split ramus osteotomy advancement. CBCT images were taken before surgery
      (T0), immediately after surgery (T1), and postoperatively at 6 months (T2) and 1
      year (T3). Condylar resorption was observed in 21 condyles. The posterior was the
      most affected region, while the anterior was the least affected. The volume of
      the glenoid cavity was significantly increased after surgery regardless of the
      presence or absence of resorption. However, the cavity recovered close to its
      original volume over time. At 1 year after surgery, the volume was not
      significantly different from the preoperative volume. Counterclockwise rotation
      of the proximal segment was found to be a risk factor affecting resorption based
      on correlation analysis. Mandibular advancement appeared to generate excessive
      mechanical stress on the posterior condyle, and might be responsible for the
      resorption. Counterclockwise rotation might have added stress to the region.
      Articular spatial change was transient and did not appear to be related to
      condyle resorption.

PMID- 30196857
TI  - Validation of a low-cost laser scanner device for the assessment of three
      dimensional facial anatomy in living subjects.
AB  - The present study compared the reliability of a low-cost laser scanner device to
      an already-validated stereophotogrammetric instrument. Fifty volunteers underwent
      duplicate facial scans through laser scanner and stereophotogrammetry. Intra- and
      inter-instrument reproducibility of linear distances, angles, facial surface area
      and volume was verified through the Bland-Altman test and calculation of absolute
      (TEM) and relative (rTEM) technical errors of measurement; rTEM was then
      classified as follows: <1% excellent; 1-3.9% very good; 4-6.9% good; 7-9.9%
      moderate; >10% poor. The scans performed through different devices were
      registered and superimposed to calculate the root mean square (RMS) (point-to
      point) distance between the two surfaces. The same protocol was applied to a
      mannequin head. In inter-instruments comparison, 12/26 measurements showed a
      "good" rTEM; 5 were "very good". In intra-instrument comparison, most
      performances worsened, with only 10 of 26 measurements classified as "good" and
      "very good". All the measurements made on mannequin scans were at least "good",
      and 14/26 were "very good". Surface area was "very good" only in intra-instrument
      comparison; conversely, volumes were poorly repeatable for all the comparisons.
      On average, RMS point-to-point distances were 0.65 mm (inter-devices comparison),
      0.56 mm (mannequin scans), 0.42 mm (intra-device comparison). In conclusion, the
      low-cost laser scan device can be reliably applied to inanimate objects, but does
      not meet the standards for three-dimensional facial acquisition on living
      persons.

PMID- 30196858
TI  - Pediatric facial injuries: Hitting close to home.
AB  - PURPOSE: The aims of this study were as follows: To determine the national
      incidence of facial fractures among infants, toddlers, and children; to evaluate
      the types of facial fractures; and to analyze common products/activities
      associated with the fractures. MATERIALS AND METHODS: A retrospective review was
      conducted to explore patterns of facial fractures among infants (<1 year),
      toddlers (1-3 years), and children (3-5 years), using the National Electronic
      Injury Surveillance System (NEISS) from the Consumer Product Safety Commission
      (CPSC). The database was searched for emergency department (ED) visits involving
      facial fractures sustained by children 1 month through 5 years of age from 2004
      through 2016 and analyzed for patient demographics, primary diagnosis and
      associated products/activities. Subset analyses were performed between age groups
      to determine the relationship between causes of injury and age using extrapolated
      national incidences. RESULTS: A total of 1507 ED visits for facial fractures
      among infants, toddlers, and children were obtained and extrapolated to an
      estimated total of 39,388 ED visits, averaging 3030 annually. The majority of
      these ED visits were for facial fractures that occurred at home. Most facial
      fractures sustained at the age period of 1 month-5 years old were nasal
      fractures. Facial fractures in infants were caused most commonly by floors or
      flooring materials, likely due to falls, while household items/furniture-related
      injuries were the most common cause of facial fractures in both toddlers and
      children. Facial fractures from playground equipment and riding toys were more
      common in children than in the other age groups. CONCLUSION: The reported trends
      in the incidence by age group and types of fracture can assist physicians by
      serving as supplement for clinical history and examination when encountering this
      challenging patient population. Our findings highlight preventative
      opportunities, particularly in baby care items and beds for reducing facial
      fractures in infants. Similarly, preventative opportunities are highlighted in
      household items and furniture for lowering the incidence of facial fractures in
      toddlers and children. Our study also suggests ensuring safe handling of
      playground equipment and riding toys for the prevention of facial fractures in
      children.

PMID- 30196859
TI  - An experimental study on antitumoral effects of KI-21-3, a synthetic fragment of
      antimicrobial peptide LL-37, on oral squamous cell carcinoma.
AB  - PURPOSE: The aim of this study was to investigate the oncolytic properties of KI
      21-3, a shortened fragment of LL-37, against oral squamous cell carcinoma (OSCC)
      in an animal model. MATERIALS AND METHODS: Twelve athymic nude mice were divided
      into a therapy and a control group of six animals each. In both groups, SCC-4
      cells were administered extraorally into the floor of the mouth in order to
      create an OSCC model. In the study group, KI-21-3 was applied intravenously
      during the 8th and 9th weeks. The subjects in the control group were injected
      with phosphate buffered saline solution in the same manner. During an examination
      period of 12 weeks, weight control was performed twice a week. Tumor growth was
      further controlled volumetrically via ultrasonography once a week with regular
      intervals. Following sacrifice, ablated tumoral tissues were
      immunohistochemically evaluated in order to determine the proliferation and
      apoptotic properties. RESULTS: The mean tumor weight in the AMP group was 0.0236
      +/- 0.023 g, which was 30% lower than the control group with the mean value of
      0.01651 +/- 0.012 g. In the control group, the approximate number of the
      proliferating cells per visualized field was fourfold higher compared to the
      therapy group. Moreover, in the control group, the number of apoptotic cells per
      visualized field was significantly lower compared to the therapy group.
      CONCLUSION: KI-21-3 showed considerable oncolytic properties on SCC-4 carcinoma
      cells via antiproliferative and caspase-3 apoptotic pathway. Further
      investigations are necessary to clarify the dose-dependent effects of this agent.

PMID- 30196860
TI  - Combining autologous bone marrow mononuclear cells seeded on collagen sponge with
      Nano Hydroxyapatite, and platelet-rich fibrin: Reporting a novel strategy for
      alveolar cleft bone regeneration.
AB  - INTRODUCTION: The aim of this study was to examine and assess the use of
      autologous bone marrow mononuclear cells (BMMNCs) combined with platelet-rich
      fibrin (PRF) and nanohydroxyapatite for bone regeneration as an effective
      technique for alveolar cleft repair. PATIENTS AND METHODS: This study included 20
      patients with unilateral alveolar cleft defects and with an age range of 8-15
      years. They were divided equally into two groups: Group A, received treatment via
      the regenerative approach which includes; autologous BMMNCs seeded on a collagen
      sponge in combination with nanohydroxyapatite and autologous PRF. Group B,
      received the standard alveolar bone grafting with iliac crest bone. The
      effectiveness of the new technique was evaluated and compared to the standard
      grafting technique through a 12-month follow-up via clinical and radiographic
      assessments. RESULTS: During the 12-month follow-up, Group A exhibited less donor
      site complications, faster and better soft tissue healing, and less postoperative
      pain, when compared to group B. 90% of the cases in group A, exhibited complete
      alveolar bone union verses 70% only in group B. CONCLUSION: Combination of
      BMMNCs, nanohydroxyapatite, and PRF greatly promote bone regeneration in alveolar
      cleft defects providing an alternative novel therapeutic strategy to the standard
      alveolar bone grafting.

PMID- 30196861
TI  - Biofunctionalization of synthetic bone substitutes with angiogenic stem cells:
      Influence on regeneration of critical-size bone defects in an in vivo murine
      model.
AB  - PURPOSE: The aim of this study was to investigate the influence of human bone
      marrow-derived endothelial progenitor cells (EPC) on vascularization and bone
      regeneration in combination with a bone-substitute material (BSM) in a critical
      size bone defect in a murine model. Critical-size bone defects were performed and
      the defects were filled according to the group membership. MATERIALS AND METHODS:
      Eighteen rats were randomized in two experimental groups: BSM (BoneCeramic)
      with/without EPC biofunctionalization, and a control group without BSM and EPC.
      Calvaria bone defects were performed and the defects were filled according to the
      group membership. After 8 weeks, qualitative tissue response of newly formed bone
      mass was analyzed by histology, cone beam CT (CBCT) and micro-CT (MUCT) scans.
      Occurrence of tumor masses due to EPC vascularization in peripheral organs was
      investigated microscopically in histological slides of liver and kidney. RESULTS:
      The combination of EPC and BSM showed smaller bone defects in the CT scans and
      the histological evaluation as the single use of BSM without EPC by trend (p =
      0.067). Further, a higher amount of blood vessels could be found in histological
      slices of BSM in combination with EPC. No inflammatory response or tumor
      formation could be found. CONCLUSION: These findings confirm the biocompatibility
      of the used BSM and provide evidence that the combination of BSM with EPC might
      be effective for bone vascularization and regeneration. Using EPC in augmentation
      sites might overall lead to faster and better bone regeneration and should be
      further investigated in future studies.

PMID- 30196862
TI  - Microvascular reconstruction in the vessel depleted neck - A systematic review.
AB  - Surgical therapy is the gold standard in head and neck cancer treatment, whereas
      adjuvant radiation and chemotherapy may be indicated in advanced cases.
      Frequently, neck dissections, former flap anastomoses and irradiated tissue leave
      a neck depleted of recipient vessels. If further surgery becomes inevitable the
      surgeon is faced with a heavily pretreated surgical field asking for highly
      reliable solutions for microsurgical reconstruction. From September 2017 until
      October 2017, a standardised review on the literature of the databases PubMed,
      Cochrane Library and Web of Science was performed. The primary research led to
      1.614 articles, an evaluation by comprehensive content resulted in 26 suitable
      articles. Overall, 325 patient cases were included in the study. 112 postsurgical
      complications were noted (34.5%) and 12 deaths were reported (3.7%). The most
      common flaps harvested were the anterolateral-thigh flap (n = 85, 25.8%), the
      radial forearm flap (n = 78, 23.7%) and the flaps from the trunk (n = 31, 9.4%).
      The arteries most frequently used for anastomosis were the internal mammary
      artery (n = 81; 28%), the transverse cervical artery (n = 46; 15.9%) and the
      superficial temporal artery (n = 43; 14.9%). The cephalic vein (n = 84; 25.9%),
      the internal mammary vein (n = 79; 24.4%) and the superficial temporal vein (n =
      50; 15.4%) were the most successfully applied veins.

PMID- 30196863
TI  - The prognostic relevance of lymph node ratio in patients with oral squamous cell
      carcinoma treated with neoadjuvant therapy regimen and radical surgery.
AB  - BACKGROUND: This study aims at investigating the prognostic significance of lymph
      node ratio (LNR) in a cohort of patients with oral squamous cell carcinomas
      (OSCC), treated with neoadjuvant radiochemotherapy followed by radical surgery.
      METHODS: The study included 171 treatment-naive patients with biopsy-proven
      primary OSCC, being reviewed retrospectively. All patients received a concomitant
      neoadjuvant radiochemotherapy (RCT) followed by radical surgery of the primary
      tumor and neck dissection based on the pretreatment staging results. The Kaplan
      Meier survival analysis method was used to estimate the events of interest for
      overall survival (OS). Prognostic factors were identified through univariate and
      multivariate analysis. RESULTS: The 5-year overall survival rate for all patients
      was 48 %. In univariate analysis, patient's age and data compiled from the
      histopathological examination as margin status, extracapsular spread, ypT, ypN,
      ypUICC, number of positive lymph nodes and lymph node ratio (LNR) had a
      statistically significant impact on overall survival. Multivariate analysis
      revealed an independent significant impact of patient age, ypT, margin status and
      LNR on OS. ypN showed no statistical significant impact on OS. CONCLUSION: Our
      results show that LNR is an important predictor for OS in patients with OSCC that
      were treated with neoadjuvant radiochemotherapy and radical surgery.

PMID- 30196864
TI  - Primary Prevention of Mood Disorders: A Primary Concern That Requires Urgent
      Action.
AB  - Among mental disorders in youth, mood disorders contribute the greatest burden.
      With a multifactorial etiology and a developmental trajectory, mood disorders
      have myriad manifestations; hence, preventative approaches have to be equally
      diverse.

PMID- 30196865
TI  - Parental Psychiatric Symptoms and Children's Outcomes: Toward Understanding and
      Responding to Intergenerational Risk in Child Psychiatry.
AB  - Family history of psychiatric illness is a core feature of any competent clinical
      history taken in a child and adolescent psychiatry clinical setting, and this
      history is often limited to reviewing caregivers' reports of diagnosed or
      suspected mental disorders in biological parents and relatives across several
      generations. Less commonly included is a detailed inquiry into parents' and
      caregivers' current mental health, including psychiatric symptoms at the time
      that their child is presenting for evaluation. Recent evidence is a strong
      reminder that parental mental illness is an important adversity that critically
      affects lifelong mental well-being in offspring, and that maternal depression in
      particular is an established factor influencing offspring mental health.1-3 In
      this issue of the Journal, Wesseldijk et al. present their article "Do Parental
      Psychiatric Symptoms Predict Outcome in Children With Psychiatric Disorders? A
      Naturalistic Clinical Study," an effort to examine relationships between parental
      psychiatric symptoms and clinical outcomes in child psychiatric patients.4 The
      study moves beyond a focus on maternal depression as a risk factor for offspring
      psychopathology to include a range of active psychiatric symptomatology in both
      mothers and fathers at the time that children are presenting for clinical
      evaluation, and again at follow-up over a year and a half later.

PMID- 30196866
TI  - Spontaneous Thoughts and Brain Connectivity: Possible Links Between Early
      Maltreatment and Later Depression.
AB  - Maltreatment (MT) during childhood wreaks lasting havoc on the developing central
      nervous system and is one of the most salient risk factors for numerous
      psychiatric disorders, including depression.1 Early intervention and prevention
      strategies to improve outcomes of youth who have experienced MT are sorely
      needed; advancement in this area will require a deeper understanding of the
      neurobiological trajectory between the occurrence of MT and the later emergence
      of illness. One approach is to select neurobiological measures that are known to
      be impaired in the fully fledged disorder and use them to assess youth with a
      history of MT who have not yet shown impairment. In depression research, an
      emerging research area is to study spontaneously generated thoughts that occur
      while awake but at unstructured times, when thoughts tend to wander. Mind
      wandering has been linked with intelligence, creative thought generation, and
      resting-state functional connectivity within the default mode network.2 However,
      in depression, these wandering thoughts can get stuck on negative content3,4 and
      could represent a core feature of the illness. Therefore, examination of
      spontaneously generated thoughts, and their neural correlates, is a promising
      avenue for research seeking precursors of depression in youth with a history of
      MT.

PMID- 30196867
TI  - Child Abuse and Neglect.
AB  - Physical, sexual, and emotional abuse and various forms of neglect of children
      are associated with substantially increased risk for concurrent and subsequent
      psychopathology and are among the common problems encountered by clinicians in
      many clinical settings. Such cases pose additional challenges for clinicians
      because of the many complex family and system forces that engulf these children
      and their families. Assessing maltreated children generally requires more time
      than evaluations of children who have not experienced maltreatment. Young
      children, who experience the highest rates of maltreatment, present especially
      complex assessments because they are so dependent upon their caregiving
      environments. Treatment of psychopathology associated with maltreatment, which is
      often multimodal, requires addressing a variety of external factors that may
      perpetuate or exacerbate symptoms and impaired functioning. We suggest that the
      more clinicians understand the different cultures of the legal and child
      protective services systems will help them advocate more effectively for
      maltreated children's bests interests so that the complexity of their problems is
      matched by the comprehensiveness of our efforts to minimize their suffering,
      enhance their development, and promote their competence.

PMID- 30196868
TI  - A Meta-Analysis of Maternal Prenatal Depression and Anxiety on Child
      Socioemotional Development.
AB  - OBJECTIVE: Observed associations between maternal prenatal stress and children's
      socioemotional development have varied widely in the literature. The objective of
      the current study was to provide a synthesis of studies examining maternal
      prenatal anxiety and depression and the socioemotional development of their
      children. METHOD: Eligible studies through to February 2018 were identified using
      a comprehensive search strategy. Included studies examined the association
      between maternal prenatal depression or anxiety and the future development of
      their children's socioemotional development (eg, difficult temperament,
      behavioral dysregulation) up to 18 years later. Two independent coders extracted
      all relevant data. Random-effects meta-analyses were used to derive mean effect
      sizes and test for potential moderators. RESULTS: A total of 71 studies met full
      inclusion criteria for data analysis. The weighted average effect size for the
      association between prenatal stress and child socioemotional problems was as
      follows: odds ratio (OR) = 1.66 (95% CI = 1.54-1.79). Effect sizes were stronger
      for depression (OR = 1.79; 95% CI = 1.61-1.99) compared to anxiety (OR = 1.50;
      95% CI = 1.36-1.64). Moderator analyses indicated that effect sizes were stronger
      when depression was more severe and when socio-demographic risk was heightened.
      CONCLUSION: Findings suggest that maternal prenatal stress is associated with
      offspring socioemotional development, with the effect size for prenatal
      depression being more robust than for anxiety. Mitigating stress and mental
      health difficulties in mothers during pregnancy may be an effective strategy for
      reducing offspring behavioral difficulties, especially in groups with social
      disadvantage and greater severity of mental health difficulties.

PMID- 30196869
TI  - Two-Year Follow-Up of Internet and Telephone Assisted Parent Training for
      Disruptive Behavior at Age 4.
AB  - OBJECTIVE: To determine whether an internet-based and telephone-assisted parent
      training intervention, which used whole population screening and which
      comprehensively targeted symptomatic 4-year-old children, was effective 24 months
      after the start of treatment. No long-term follow-up studies using a randomized
      controlled trial (RCT) existed on this subject. METHOD: Of the 4,656 children 4
      years old who were screened in Southwest Finland, 730 met the criteria for high
      level disruptive behavioral problems, and 464 parents agreed to be randomized to
      the 11-week Strongest Families Smart Website (SFSW) intervention (n = 232) or an
      educational control (EC) (n = 232). After 24 months, 163 SFSW parents (70%) and
      165 EC parents (71%) were still participating. RESULTS: When we compared the
      results at baseline and 24 months, the primary outcome of the Child Behavior
      Checklist (CBCL) externalizing score showed significantly higher improvements in
      the SFSW group (effect size 0.22; p < 0.001). This group also showed greater
      improvements in the secondary outcomes: the CBCL total and internalizing scales,
      5 of the 7 CBCL symptom domains, 3 of the 5 DSM subscores, and self-reported
      parenting skills. Fewer SFSW children (17.5%) than EC children (28.0%) had been
      referred to child mental health services between baseline and 24 months (odds
      ratio = 1.8; 95% confidence interval = 1.1-3.1). CONCLUSION: The SFSW internet
      based and telephone-assisted parental training program was effective 24 months
      after initiation, underlining the value of identifying children at risk in the
      community early and providing evidence-based parent training for a large number
      of families. CLINICAL TRIAL REGISTRATION INFORMATION: STRONGEST FAMILIES FINLAND
      CANADA: Family-based Prevention and Treatment Program of Early Childhood
      Disruptive Behavior (Fin-Can). http://www.clinicaltrials.gov; NCT01750996.

PMID- 30196870
TI  - Do Parental Psychiatric Symptoms Predict Outcome in Children With Psychiatric
      Disorders? A Naturalistic Clinical Study.
AB  - OBJECTIVE: Parental psychiatric symptoms can negatively affect the outcome of
      children's psychopathology. Studies thus far have mainly shown a negative effect
      of maternal depression. This study examined the associations between a broad
      range of psychiatric symptoms in mothers and fathers and the child's outcome.
      METHOD: Internalizing and externalizing psychiatric symptoms were assessed in 742
      mothers, 440 fathers, and their 811 children at the first evaluation in 3 child
      and adolescent psychiatric outpatient clinics and at follow-up (on average 1.7
      years later). Predictions of child's symptoms scores were tested at follow-up by
      parental symptom scores at baseline, parental scores at follow-up, and offspring
      scores at baseline. RESULTS: Children whose mother or father scored above the
      (sub)clinical threshold for psychiatric symptoms at baseline had higher symptom
      scores at baseline and at follow-up. Offspring follow-up scores were most
      strongly predicted by offspring baseline scores, in addition to parental
      psychiatric symptoms at follow-up. Offspring symptom scores at follow-up
      generally were not predicted by parental scores at baseline. Maternal and
      paternal associations were of similar magnitude. CONCLUSION: Higher symptom
      scores at follow-up in children of parents with psychopathology were mainly
      explained by higher symptom scores at baseline. Continuing parent-offspring
      associations could be a result of reciprocal effects, ie, parental symptoms
      influencing offspring symptoms and offspring symptoms influencing parental
      symptoms. Nevertheless, the results show that these children are at risk for
      persisting symptoms, possibly indicating the need to treat maternal and paternal
      psychopathology.

PMID- 30196871
TI  - Interaction Between Parenting Styles and Adrenarcheal Timing Associated With
      Affective Brain Function in Late Childhood.
AB  - OBJECTIVE: Parenting and pubertal timing have consistently been associated with
      internalizing and externalizing symptoms in childhood and adolescence, and there
      is some evidence that the interaction between these factors may be important in
      conferring risk. However, few studies have investigated whether neurobiological
      factors mediate these relationships. The current study examined whether
      interactions between adrenarcheal timing and parenting styles were associated
      with affective brain function and, in turn, mental health difficulties. METHOD:
      Participants were 88 healthy children (46 female and 42 male, mean age 9.42
      years, SD = 1.08 years), with 45 classified as relatively early and 43 as
      relatively late in adrenarcheal development based upon adrenal hormone levels.
      Participants completed an affective face functional magnetic resonance imaging
      task, and parents reported on 5 parenting styles and on child internalizing and
      externalizing symptoms. RESULTS: Negative parenting styles (corporal punishment
      and poor monitoring) were associated with brain hemodynamic response while
      viewing affective faces in several subcortical and lateral prefrontal regions,
      and adrenarcheal timing and/or sex moderated most of these relationships. Sex
      differences in associations between corporal punishment and brain activation to
      affective faces indicated that late females might show less adaptive affective
      neural function when more exposed to this parenting style. CONCLUSION: Findings
      suggest that the interaction between parenting styles and adrenarcheal timing is
      associated with affective brain function in late childhood, with marked sex
      differences. Further longitudinal research with larger samples is needed to
      corroborate and expand upon these findings.

PMID- 30196872
TI  - Evidence for Depressogenic Spontaneous Thoughts and Altered Resting-State
      Connectivity in Adolescents With a Maltreatment History.
AB  - OBJECTIVE: Childhood maltreatment has been associated with major depressive
      disorder (MDD). Atypical self-generated thoughts (SGT), lacking in positive and
      privileging negative content-a feature of ruminative thinking-might represent one
      vulnerability factor for developing depression. Rumination in MDD has been linked
      to alterations in resting-state functional connectivity (RSFC) of the subgenual
      anterior cingulate cortex (sgACC) to the default mode network and the fronto
      parietal network (FPN). This study aimed to investigate online SGT content and
      its variability, as well as sgACC RSFC, as potential risk markers for depression
      in adolescents who experienced maltreatment. METHOD: Adolescents 12 to 16 years
      old (29 with maltreatment history [MT] and 39 with no maltreatment history [NMT])
      performed an established mind-wandering task. Participants made nondemanding
      number discriminations during which intermittent questions probed their SGTs that
      were classified as off-task, positive, negative, self-related, other-related,
      past-oriented, or future-oriented. Resting-state data were acquired separately
      for 22 of 29 MT and 27 39 NMT adolescents, and seed-based functional connectivity
      analyses of the sgACC were performed. RESULTS: MT, relative to the NMT
      adolescents, generated significantly fewer positively valenced thoughts, and
      exhibited more extreme ratings for positively valenced thoughts. MT adolescents
      also showed significantly reduced RSFC between the sgACC and the FPN. Group
      differences in depressive symptoms between the MT and NMT adolescents were partly
      accounted by differences in sgACC-FPN RSFC. CONCLUSION: Adolescents who
      experienced maltreatment show a reduction in positively valenced spontaneous
      thoughts and reduced sgACC-FPN RSFC at the neural level. These may contribute to
      a ruminative thinking style, representing risk factors for developing depression
      later in life.

PMID- 30196873
TI  - Psychiatric Morbidity Among a School Sample of Syrian Refugee Children in Turkey:
      A Cross-Sectional, Semistructured, Standardized Interview-Based Study.
AB  - Now in its eighth year, the Syrian civil war has caused displacement of more than
      half the population before the war and is viewed as the single largest
      contributing factor to many of the worsening global trends of children living in
      areas affected by conflict.1.

PMID- 30196874
TI  - Effect of Selective Serotonin Reuptake Inhibitor Use in Pregnancy on Emotional
      Health of Children.
AB  - I read with interest the article by Lupattelli et al., "Effect of Time-Dependent
      Selective Serotonin Reuptake Inhibitor Antidepressants During Pregnancy on
      Behavioral, Emotional, and Social Development in Preschool-Aged Children,"1 which
      describes the effects of selective serotonin reuptake inhibitor (SSRI) use in
      pregnancy on mental health in offspring, in the March issue of the Journal. The
      investigators found that SSRI use in late pregnancy resulted in greater risk for
      anxious/depressed behaviors in children by 5 years of age compared with unexposed
      children.

PMID- 30196875
TI  - Dr. Lupattelli et al. Reply.
AB  - We thank Dr. Shaligram, author of this Letter to the Editor, for the interest in
      our recent article reporting time-dependent effects of prenatal exposure to
      selective serotonin reuptake inhibitors (SSRIs) on behavioral, emotional, and
      social development in offspring at age 5 years.1 Dr. Shaligram raises interesting
      points of consideration for interpretation of the study results, and poses
      methodological questions about our window of exposure classification.2.

PMID- 30196876
TI  - The Problem of Same-Rater Bias.
AB  - The diagnostic process in child and adolescent psychiatry relies heavily on
      information from multiple informants, including parents, teachers, and the child
      itself. It has long been well known that information from informants who see the
      child in different settings may differ, but that each type of informant may
      contribute useful and unique information to the prediction of mental health
      problems.1 The diagnosis of attention-deficit/hyperactivity disorder (ADHD)
      depends on reports from informants who see the child in different settings. This
      is illustrated in the DSM-5, in which the diagnostic criteria require several
      inattentive or hyperactive-impulsive symptoms to be present in two or more
      settings.

PMID- 30196877
TI  - Dr. Overgaard et al. Reply.
AB  - We appreciate that Rimvall et al. read our latest article with interest.1 Early
      and accurate screening of attention-deficit/hyperactivity disorder (ADHD) is
      important for the remediation of the disorder. Clinicians' lack of time has been
      identified as a barrier to screening for behavioral disorders.2 A short screener
      such as the Strengths and Difficulties Questionnaire (SDQ) hyperactivity
      inattention (HI) subscale holds the potential to improve detection of ADHD in
      preschoolers. Rimvall et al. make the point that diagnosing children with ADHD
      requires a broader assessment that includes information from parents, teachers,
      and the child. We agree, except to say that 3-year-old children are too young to
      provide information.

PMID- 30196878
TI  - The Body and the Traumatic Real.
AB  - The symbol (word) first manifests itself as the killing of the thing...-Jacques
      Lacan1 This month our books and reviewers challenge us to examine the mental
      worlds and lived experience of women whose bodies are brutalized, pushed to
      extremes of overeating and undereating, of wishing to shout yet being unable to
      say a word. Nathalie Szilagyi reviews writer and feminist Roxane Gay's Hunger, a
      memoir detailing the author's struggles with self-acceptance and her body in the
      aftermath of severe trauma. In her review, Szilgayi asks us to imagine how we can
      help people facing situations like that of Gay, in ways more affirming and
      effective. Meanwhile, Michael Goldenberg, Kimberly Myers, and Jennifer Aengst
      examine three graphic memoirs and novels (Ink in Water, Lighter Than My Shadow,
      Speak: The Graphic Novel). They encourage us to look beyond our patients' speech
      balloons, affects, and exteriors, imagining the thought bubbles that loom
      overhead.

PMID- 30196879
TI  - Corrigendum.

PMID- 30196880
TI  - Advancing Nutrition Education Research and Practice.

PMID- 30196881
TI  - Being Responsive to Parents' Concerns About Fussy Eaters.

PMID- 30196882
TI  - Concern Explaining Nonresponsive Feeding: A Study of Mothers' and Fathers'
      Response to Their Child's Fussy Eating.
AB  - OBJECTIVE: To examine the role of parent concern in explaining nonresponsive
      feeding practices in response to child fussy eating in socioeconomically
      disadvantaged families. DESIGN: Mediation analysis of cross-sectional survey
      data. SETTING: Socioeconomically disadvantaged urban community in Queensland,
      Australia. PARTICIPANTS: Cohabiting mother-father pairs (n = 208) with children
      aged 2-5 years. MAIN OUTCOME MEASURE(S): Two validated measures of nonresponsive
      feeding: persuasive feeding and reward for eating. ANALYSIS: Mediation analysis
      tested concern as a mediator of the relationship between child food fussiness
      (independent variable) and parent nonresponsive feeding practices (dependent
      variables), adjusted for significant covariates and modeled separately for
      mothers and fathers. RESULTS: Maternal concern fully mediated the relationship
      between child food fussiness and persuasive feeding (indirect effect: B [SE] =
      0.10 [0.05]; 95% confidence interval [CI], 0.01-0.20). Concern also fully
      mediated the relationship between child food fussiness and reward for eating for
      mothers (indirect effect: B [SE] = 0.17 [0.07]; CI, 0.04-0.31) and fathers
      (indirect effect: B [SE] = 0.14 [0.05]; CI, 0.04-0.24) CONCLUSIONS AND
      IMPLICATIONS: Concern for fussy eating behaviors may explain mothers' and
      fathers' nonresponsive feeding practices. In addition to providing education and
      behavioral support, health professionals working with socioeconomically
      disadvantaged families can incorporate strategies that aim to alleviate parents'
      concerns about fussy eating.

PMID- 30196883
TI  - Pilot-Testing an Intervention to Enhance Wellness Policy Implementation in
      Schools: Wellness Champions for Change.
AB  - OBJECTIVE: To develop and pilot-test Wellness Champions for Change (WCC) to
      enhance local wellness policy (LWP) implementation by forming wellness teams.
      DESIGN: Randomized, controlled school-level pilot study. SETTING: Five Maryland
      school districts. PARTICIPANTS: A total of 63 elementary, middle, or high
      schools. INTERVENTION(S): Developed from stakeholder interviews, focus groups,
      and existing programs. Schools were randomized within district to (1) WCC
      training (6-hour, single-day teacher training), (2) WCC training plus technical
      assistance (TA), or (3) delayed training (control). MAIN OUTCOME MEASURE(S):
      Online teacher/administrator survey pre-post (spring, 1 year apart) that examined
      the direct effect of the intervention on active wellness team formation
      (postintervention, 8-item sum score) and LWP implementation (29 items, not
      implemented to fully implemented)/indirect effect of intervention on LWP
      implementation via active wellness team formation. ANALYSIS: Adjusted linear or
      logistic regression and mediation modeling. RESULTS: Postintervention, WCC plus
      TA and WCC had more active wellness teams (vs control, beta = 1.49, P = .02 and
      beta = 1.42, P = .03, respectively). No direct effect of intervention on LWP
      implementation was found. Formation of active wellness teams mediated the
      association between both WCC plus TA and WCC and LWP implementation (WCC plus TA
      confidence interval [CI], 1.22-16.25; WCC CI, 10.98-15.61 [CI was significant
      without 0]). CONCLUSIONS AND IMPLICATIONS: The WCC intervention approaches
      indirectly affected LWP implementation through the formation of active wellness
      teams. These results support building and school-level wellness teams.

PMID- 30196884
TI  - Acculturation and Food Insecurity Among Puerto Ricans Living in Boston.
AB  - OBJECTIVE: To examine the associations among acculturation, food environment, and
      food insecurity among Puerto Ricans in Boston. METHODS: The researchers used data
      from the second wave of the Boston Puerto Rican Health Study. The sample included
      719 Puerto Rican adults in Boston. The researchers used logistic regression to
      examine the associations between psychological and language acculturation and
      food insecurity. RESULTS: Individuals with medium psychological acculturation
      were more likely to be food insecure than were those with low or high
      psychological acculturation (P = .01). The association between language
      acculturation and food insecurity differed by distance of residence from primary
      shopping location (P = .02). CONCLUSIONS AND IMPLICATIONS: This study extends the
      understanding of acculturation and food insecurity by investigating the impact of
      psychological and language acculturation. The findings highlight biculturalism,
      indicated by medium psychological acculturation, as a risk factor for food
      insecurity. People with low language acculturation who live far from food
      shopping locations had the highest prevalence of food insecurity.

PMID- 30196886
TI  - Foreword.

PMID- 30196885
TI  - [An audit of preventable hospital admissions due to heart failure in a primary
      care district].

PMID- 30196887
TI  - Sex and gender in Alzheimer's disease - Does it matter?

PMID- 30196888
TI  - Screening of cold tolerance in fifteen springtail species.
AB  - Springtails (Collembola) are ubiquitous and help ecosystem processes such as the
      decomposition of dead plant material. Their ability to survive low winter
      temperatures is an important trait that partly defines their geographic
      distribution. The cold tolerances of 15 laboratory-reared species of springtails
      were investigated. Springtails were cold acclimated in the laboratory over two
      months in order to simulate a seasonal change in temperature during autumn.
      Springtails were then exposed to decreasing sub-zero temperatures and at the same
      time simulating the moisture conditions in frozen soil. The cold tolerance of the
      species reflected well the climate of region of origin. Differential scanning
      calorimetry of individual springtails showed that melting points of body fluids
      did not become lower due to long-term cold acclimation (from 20 degrees  to 1.5
      degrees C). However, both water content and melting point of two arctic species
      (Hypogastrura viatica and Protaphorura macfadyeni) decreased drastically during
      exposure to sub-zero temperatures indicating cryoprotective dehydration (CPD).
      These arctic species survived exposure to - 9  degrees C for two weeks and - 20 
      degrees C for at least one week using CPD. Four other subarctic or cool temperate
      species also used CPD and survived - 9  degrees C for weeks, whereas springtails
      in culture from less cool temperate regions had poor cold tolerance.

PMID- 30196889
TI  - Dietary nano-silver: Does support or discourage thermal tolerance and biochemical
      status in air-breathing fish reared under multiple stressors?
AB  - Unexpected fluctuations in weather parameters due to global climate change have
      been observed in all ecosystems worldwide. The aquatic ecosystem shelters a great
      diversity of fishes in the upper region of the ecosystem which adversely get
      affected due to their poikilothermic nature. The present study was designed to
      elucidate the impact of critical temperature minima (CTMin), lethal temperature
      minima (LTMin), critical temperature maxima (CTMax), and lethal temperature
      maxima (LTMax) on Channa striatus. Biologically synthesized silver nanoparticles
      (Ag-NPs) were evaluated for their potential to enhance thermal tolerance and
      improve the activities of biochemical enzymes of C. striatus reared under lead
      (Pb) and high temperature (34  degrees C) for 50 days. Three iso-caloric and iso
      nitrogenous diets which included a basal diet and two supplemented diets with Ag
      NPs @ 0.5 mg/kg, and 1 mg/kg were used in the study. Results suggested that CTMin
      and LTMin were significantly (p < 0.01) reduced and CTMax and LTMax were enhanced
      in the group fed with 0.5 mg/kg Ag-NPs supplemented feed. Pre-exposure to high
      temperature led to enhanced CTMax and LTMax in C. striatus. The biochemical
      enzymes involved in protein metabolism, carbohydrate metabolism, acetylcholine
      esterase and antioxidant activities were found to be normal in fish fed with 0.5
      mg/kg Ag-NPs supplemented diet. Bioaccumulation of silver and Pb was determined
      in different fish tissues and experimental water. Overall, the incorporation of
      Ag-NPs at 0.5 mg/kg in diet can confer protection to fish against Pb and thermal
      stress and enhance thermal tolerance of C. striatus.

PMID- 30196890
TI  - Chronic heat stress increases insulin-like growth factor-1(IGF-1) but does not
      affect IGF-binding proteins in growing pigs.
AB  - The insulin-like activity of insulin-like growth factor-1 (IGF-1) is heavily
      blunted by IGF binding proteins (IGFBPs, including IGFBP-1 and IGFBP-3). The
      effects of heat stress (HS) on the IGF-1 and IGFBPs in growing pigs are still not
      clear. This study aimed to investigate the alterations of IGF-1 and IGFBPs under
      chronic HS in growing pigs. Twenty-seven growing large white barrows with similar
      body weight were collected from nine litters and were assigned into three
      treatments. The litter effect is balanced in all treatments. Treatments were: 1)
      thermal-neutral (TN) group (23  degrees C), 2) chronic HS group (33  degrees C),
      and 3) pair-fed in TN condition (PFTN). The experiment lasted for 21 days.
      Compared with TN controls, decreased FI, lower average body weight gain, higher
      rectal temperature and increased respiration rates were observed in HS pigs. On
      D7, increased plasma insulin concentration and insulin:glucose ratio were
      observed in HS pigs compared to TN controls. A overall elevation of plasma IGF
      1:IGFBP-3 ratio was detected in HS pigs compared with PFTN and TN counterparts.
      Besides, hepatic IGF-1 gene expression of HS pigs was 50% higher than TN
      counterparts. PFTN pigs, however, had no differences in plasma IGF-1:IGFBP-3
      ratio and hepatic IGF-1 gene expression, compared with TN pigs. PFTN pigs
      increased plasma IGFBPs concentration and hepatic IGFBPs gene expression,
      compared with TN controls. However, no differences in plasma IGFBPs concentration
      and hepatic IGFBPs gene expression were observed between TN and HS group. Liver
      IRS-1 gene and protein expressions of HS pigs tended to be increased compared
      with TN controls, while PFTN pigs still kept liver IRS-1 gene and protein
      expressions in normal level. High temperature (33  degrees C), independent of
      feed intake reduction, increased IGF-1 but did not affect IGFBPs levels in
      growing pigs.

PMID- 30196891
TI  - Effect of the trabecular bone microstructure on measuring its thermal
      conductivity: A computer modeling-based study.
AB  - The objective of this work is to quantify the relation between the value of the
      effective thermal conductivity of trabecular bone and its microstructure and
      marrow content. The thermal conductivity of twenty bovine trabecular bone samples
      was measured prior to and after defatting at 37, 47, and 57  degrees C. Computer
      models were built including the microstructure geometry and the gap between the
      tissue and measurement probe. The thermal conductivity (k) measured was 0.39 +/-
      0.06 W m-1 K-1 at 37  degrees C, with a temperature dependence of + 0.2% degrees
      C-1. Replacing marrow by phosphate-buffered saline (defatting) increased both the
      computer simulations and measurement results by 0.04 W m-1 K-1. The computer
      simulations showed that k increases by 0.02-0.04 W m-1 K-1 when the model
      includes a gap filled by phosphate-buffered saline between the tissue and
      measurement probe. In the presence of microstructure and fatty red marrow, k
      varies by +/- 0.01 W m-1 K-1 compared with the case considering matrix only,
      which suggests that there are no significant differences between cortical and
      trabecular bone in terms of k. The computer results showed that the presence of a
      gap filled by phosphate-buffered saline around the energy applicator changes
      maximum temperature by < 0.7  degrees C, while including the bone microstructure
      involved a variation of < 0.2 mm in the isotherm location. Future experimental
      studies on measuring the value of k involving the insertion of a probe into the
      bone through a drill hole should consider the bias found in the simulations.
      Thermal models based on a homogeneous geometry (i.e. ignoring the microstructure)
      could provide sufficient accuracy.

PMID- 30196892
TI  - Sex difference in cold perception and shivering onset upon gradual cold exposure.
AB  - To maintain a thermal balance when experiencing cold, humans reduce heat loss and
      enhance heat production. A potent and rapid mechanism for heat generation is
      shivering. Research has shown that women prefer a warmer environment and feel
      less comfortable than men in the same thermal condition. Using the Blanketrol(r)
      III, a temperature management device commonly used to study brown adipose tissue
      activity, we tested whether the experimental temperature (TE) at which men and
      women start to shiver differs. Twenty male and 23 female volunteers underwent a
      cooling protocol, starting at 24  degrees C and gradually decreasing by 1-2 
      degrees C every 5 min until an electromyogram detected the shivering or the
      temperature reached 9  degrees C. Women started shivering at a higher TE than men
      (11.3 +/- 1.8  degrees C for women vs 9.6 +/- 1.8  degrees C for men, P = 0.003).
      In addition, women felt cool, scored by a visual analogue scale, at a higher TE
      than men (18.3 +/- 3.0  degrees C for women vs 14.6 +/- 2.6  degrees C for men, P
      < 0.001). This study demonstrates a sex difference in response to cold exposure:
      women require shivering as a source of heat production earlier than men. This
      difference could be important and sex should be considered when using cooling
      protocols in physiological studies.

PMID- 30196893
TI  - Higher environmental temperatures promote acceleration of spermatogenesis in vivo
      in mice (Mus musculus).
AB  - Temperature is considered a crucial modulator of reproductive activity and testis
      homeostasis. It is well known that elevated temperatures cause several effects on
      testicular components, particularly on germ cells, which might lead to the
      impairment of spermatogenesis and loss of male fertility. The present study aimed
      to evaluate the effects of different environmental temperatures on several
      morphofunctional testis parameters, with emphasis on duration of spermatogenesis
      and spermatogenic efficiency. Thirty sexually mature Swiss mice (Mus musculus)
      were allocated in three different experimental groups, being kept in vivarium for
      three weeks at 16  degrees C, 23  degrees C (control group) and 32  degrees C. In
      order to estimate the duration of spermatogenesis, three animals per each group
      received intraperitoneal injections of tritiated thymidine and the testes were
      perfused-fixed and routinely processed for histological, morphometrical and
      immunoperoxidase analyses. Although the lower temperature (16  degrees C) did not
      change most of the evaluated testicular parameters, our findings showed that
      higher environmental temperature (32  degrees C) is able to alter important
      testis parameters, resulting for instance in acceleration of spermatogenesis,
      alterations in the stages frequencies, increased number of germ and Leydig cells
      apoptosis and reduced Sertoli cell and spermatogenic efficiencies. As in many
      conditions infertile men exhibit higher mean scrotal temperature, we believe that
      experimental studies with mice involving temperature might represent an
      interesting approach to better understand the mechanisms related to human testis
      function and sperm production.

PMID- 30196894
TI  - Uncoupling psychological from physiological markers of heat acclimatization in a
      military context.
AB  - Heat acclimatization may help personnel who travel to areas with a hot climate
      (WBGT > 27  degrees C), making them operationally more efficient and performant
      through improvements in physiological and psychological parameters. Their work
      related physical activities may aid active heat acclimatization. However, it is
      unknown whether adding physical training to improve adaptation is effective,
      particularly if there is sufficient time for full acclimatization, classically
      reached after 15 days. Thirty French soldiers (Training group, T) performed a
      progressive and moderate (from three to five 8-min running sets at 50-60% of
      their speed at VO2max with 4-min periods of active recovery in between) aerobic
      training program upon arriving at their base in United Arab Emirates (~40 
      degrees C and 20% RH). A control group (30 soldiers; No Training, NT) continued
      to perform only their usual outdoor military activities (~5 h d-1). A field heat
      stress test (HST: three 8-min running sets at 50% of the speed at VO2max) was
      performed before (D0), during (D10), and after (D15) the heat acclimatization
      period to assess physiological and psychological changes. An 8-km trial in
      battledress was then performed at D17. Although physiological modifications were
      mostly similar (p < 0.001 for all) for both groups (rectal temperature at the end
      of the HST: -0.58 +/- 0.51 vs -0.53 +/- 0.40  degrees C, HR at the end of the
      HST: -21 +/- 12 vs -19 +/- 9 bpm, and sweat osmolality: -47 +/- 30 vs -26 +/- 32
      mOsmol.l-1 between D15 and D0 for T and NT groups, respectively), thermal
      discomfort (-31 +/- 4 vs -11 +/- 5 mm between D15 and D0, p = 0.001) and rates of
      perceived exertion (-3.0 +/- 0.4 vs -1.4 +/- 0.3 D15 and D0, p = 0.001) were much
      lower in the T than NT group during the HST. HST-induced modifications in facial
      temperature only decreased in the T group (-1.08 +/- 0.28 between D15 and D0, p <
      0.001). Moreover, there was a difference in perceived thermal discomfort during
      the 8-km trial (40 +/- 20 vs 55 +/- 22 mm for the T and NT groups, respectively,
      p = 0.010). Thus, a 15-day, low-volume training regimen during a mission in a hot
      and dry environment has a modest impact on physiological adaptation but strongly
      decreases the perceived strain of exertion and climate potentially via greater
      reductions in facial temperature, even during a classical operational physical
      task in a military context.

PMID- 30196895
TI  - Annotation of differential protein expression in the hypothalami of layer-type
      Taiwan country chickens in response to acute heat stress.
AB  - The hypothalamus is the coordinating center for maintaining temperature
      homeostasis. In this study, global protein expression in the hypothalami of layer
      type Taiwan country chickens in response to acute heat stress was investigated.
      Twelve 30-week-old female TCCs were divided into three acute heat-stressed
      groups, namely acute heat stress at 36  degrees C for 4 h with 0 h (without
      recovery, H4R0), 2 h (H4R2), or 6 h (H4R6) of recovery. A control group was
      maintained at 25  degrees C. Hypothalamus samples were collected at the end of
      each time point for proteomic analysis. The analysis results revealed that 134
      protein spots representing 118 distinct proteins exhibited differential
      expressions after acute heat stress treatment. Results of gene ontology analysis
      showed that most of the differentially expressed proteins are involved in
      carbohydrate metabolism, cellular processes, actin cytoskeleton organization, and
      responses to stimuli. Functional pathway analysis results suggested that the
      proteins are associated with networks of carbon metabolism, glycolysis, and
      gluconeogenesis. Upregulation of the expression of triosephosphate isomerase,
      phosphoglycerate kinase, pyruvate kinase, alpha-enolase, glycogen phosphorylase
      (brain form), phosphoglucomutase, L-lactate dehydrogenase A chain and
      downregulation of 6-phosphogluconolactonase expression indicated an increase in
      the glycolytic activity and glucose supply for ATP production in the hypothalami
      in response to heat stress. By contrast, upregulated expressions of heat shock
      protein 90 alpha, glutathione S-transferase 2s, peroxiredoxin-1, and
      dihydropyrimidinase-like 2 suggested that acute heat stress adversely affects the
      hypothalamus; thus, it induces mechanisms that prevent oxidative damage and
      endoplasmic reticulum stress. In conclusion, acute heat stress induces
      differential protein expression in the hypothalami of the L2 strain Taiwan
      country chickens, which may manifest detrimental effects. Furthermore,
      differential expression is a critical response in the hypothalamus for the
      regulation of thermotolerance.

PMID- 30196896
TI  - A review and quantitative assessment of cattle-related thermal indices.
AB  - Many thermal indices have been developed to assess the levels of heat stress
      imposed on cattle during hot weather. In this paper, the 16 cattle-related
      thermal indices are critically reviewed. The primary emphasis is to evaluate each
      index's coherence to the typical heat transfer characteristics of a cow. Other
      perspectives including incorporated environmental parameters in the equation(s),
      experimental data, correlated physiological responses, heat-stress thresholds,
      scope of application, specific cattle breed involved, and experiment location(s)
      are also well categorised and discussed. The coherence evaluation indicates that
      the main effects of environmental parameters on heat stress have been properly
      reflected, while some interactions between the parameters have been treated
      differently. Given the variety of the equations used to define the 16 indices and
      the wide range of information used to develop each index, we conclude that each
      thermal index is distinct to an extent that it should be selected and employed
      carefully.

PMID- 30196897
TI  - Variation of preferred body temperatures along an altitudinal gradient: A multi
      species study.
AB  - Temperature affects the physiological functions of ectotherms. To maintain
      optimal body temperature and ensure physiological performance, these organisms
      can use behavioral adjustments to keep the body temperature in their specific
      temperature range, so-called preferred temperature (Tpref). It is therefore
      crucial to describe and understand how Tpref vary within and amongst populations
      to predict the effects of climate change of altitudinal range shifts in
      organisms. We aimed at determining the altitudinal variations in Tpref in three
      ectothermic species (the Pyrenean brook salamander - a semi-aquatic and
      thigmothermic amphibian - the European common lizard and the wall lizard - both
      heliothermic species). Using an experimental approach where Tpref were measured
      along a temperature gradient in laboratory conditions, we used a cross-sectional
      approach to compare the variation of Tpref measured in populations sampled along
      the altitudinal gradient in the Pyrenees. We hypothesized a complex and highly
      variable intra-specific response of Tpref along geographical clines, with a
      positive relationship between Tpref and altitude (as predicted by the
      countergradient variation), the reverse pattern (referring to the adaptation of
      local optima hypothesis), or no relationship at all. Our results corroborated
      partially the countergradient hypothesis in the salamander (middle to high
      elevation part). At high altitude level, individuals may compensate for lower
      opportunities of favorable conditions by choosing a high temperature which
      maximizes their activities. However, populations from low elevation level hence
      better supported the adaptation of local optima hypothesis, such as both lizard
      species, for which Tpref tended instead to decrease with altitude. Lizards from
      cold climates may be physiologically adapted to low temperature, with the ability
      to reach optimal functioning at lower temperature than individuals from low
      altitude. Our findings suggest that predicting future niche models should
      therefore take into account the variability of Tpref, where species might be
      differently affected by global warming.

PMID- 30196898
TI  - Numerical investigation of the effect of vessel size and distance on the
      cryosurgery of an adjacent tumor.
AB  - Cryosurgery is an efficient cancer treatment which can be used for non-invasive
      ablation of some internal tumors such as liver and prostate. Tumors are usually
      located near the large blood vessels and the heat convection may affect the
      progression of the ice ball. Hence it is necessary to predict the surgery
      procedure and its consequences earlier. In spite of the recent studies it is
      still unclear that which arteries will significantly affect the freezing
      treatment of tumors and which can be ignored. Therefore a numerical model of a
      spherical 3 cm diameter liver tumor, subjected to cryosurgery was developed. The
      specific thermophysical properties were applied to the tumor and healthy tissues
      in frozen and unfrozen states. A simplified Hepatic artery with different
      anatomical diameters was placed in different positions relative to the tumor and
      energy and momentum equations were solved. The temperature distribution and the
      shape of the resultant ice ball were discussed. The results showed that a 4 mm
      diameter artery in the vicinity of a tumor will increase the minimum temperature
      achieved at the tumor boundary by 12.5  degrees C and therefore significantly
      affects the cryosurgery outcome. This may cause insufficient freezing which leads
      to incomplete death of tumor cells, failure of the surgery and tumor regenesis.
      Eventually it was shown that injection of gold and Fe3O4 nanoparticles to the
      surrounding tissue of the artery can enhance the heat transfer and progression of
      the ice ball, making temperature distribution similar to the no vessel state.
      Development of computational models can provide the physicians an applicable tool
      which helps them recognize how efficient a treatment method will be for a
      specific case and design a suitable cryosurgery plan.

PMID- 30196899
TI  - EPR hyperthermia of S. cerevisiae using superparamagnetic Fe3O4 nanoparticles.
AB  - Presently we communicate a newly developed method of resonant radiofrequency
      heating, applicable in hyperthermal therapy. This method uses electron
      paramagnetic resonance (EPR) to transform the electromagnetic field energy into
      heat. We report the growth dynamics of the S. cerevisiae yeast cells exposed to
      EPR heating with superparamagnetic magnetite (Fe3O4) nanoparticles, with only 4%
      of yeast cells surviving hyperthermia. Given that EPR functions independently of
      type of the biologic species exposed, and produces spatially localized heating in
      conjunction with MRI hardware, it may be used in hyperthermal therapy of cancer
      and other diseases.

PMID- 30196900
TI  - Effects of pre-exercise sucrose ingestion on thermoregulatory responses to near
      maximal 5-km running.
AB  - Research has shown that carbohydrate consumption can increase body temperature at
      rest and, in some cases, during exercise. Most exercise studies, however, haven't
      matched exercise intensity between carbohydrate and placebo conditions. The
      purpose of this randomized, double-blind, placebo-controlled trial was to examine
      whether pre-exercise carbohydrate consumption independently accelerates the usual
      temperature rise with intense exercise. Twenty-eight runners self-reported 5-km
      performance (16-23 min) and were randomized, using a matched-pairs design, to 750
      ml water containing 100 g sucrose or 0.8 g aspartame. Beverages were consumed 60
      min before running at 93% of maximum 5-km speed in temperate conditions.
      Gastrointestinal temperature, Thermal Sensation Scale (TSS) and Feeling Scale
      (FS) were recorded before ingestion, every 10 min during 60 min of rest, and
      every 1-km during the 5-km run. Rating of Perceived Exertion was recorded every 1
      km. Independent samples t-tests and two-way mixed ANOVAs with repeated measures
      assessed whether there were baseline differences or treatment effects.
      Gastrointestinal temperature didn't differ between carbohydrate (38.7 +/- 0.4 
      degrees C) and placebo (38.6 +/- 0.4  degrees C) by the end of the 5-km (p =
      0.49). No group x time interactions or main group effects were found, except for
      a modest interaction for TSS (F = 2.1, p = 0.02, partial eta2 = 0.075). Time
      effects were found for all outcomes, with temperature, TSS, and RPE increasing,
      and FS decreasing, during the run. Ingesting 100 g of sucrose prior to intense
      running lasting < 25 min didn't influence gastrointestinal temperature and
      therefore doesn't likely impact on the risk of heat illness.

PMID- 30196901
TI  - Effects of the daily heat load duration exceeding determined heat load thresholds
      on activity traits of lactating dairy cows.
AB  - In recent years, the problem of the welfare and heat load of dairy cows has
      become increasingly important in moderate climate zones. The objective of the
      present study was to determine heat load thresholds of average daily temperature
      humidity index (THI) that lead to changes in different activity traits of
      lactating high-yielding dairy cows. Furthermore, we studied how the activity of
      the cows to heat load was influenced by the daily heat load duration which
      exceeded the heat load we had determined as threshold in our experiments. The
      study was conducted from June 2015 to May 2017 in a naturally ventilated dairy
      barn in Grobeta Kreutz, Germany. The climate was measured at several positions
      inside the barn, and the average THI was calculated every 10 min. The THI was
      used to define the dairy cows' heat load exposure. In addition, the activity of
      the cows was measured by pedometers, and different activity traits were recorded
      in the functional groups "resting behavior" and "locomotion behavior". The heat
      load thresholds determined by broken-stick models were 47 THI (standing bout
      duration, number of steps) as well as 67 THI (total lying/standing time, number
      of lying/standing bouts, lying bout duration). During the experimental period,
      the most reliable heat load threshold of 67 THI was exceeded from May to
      September for up to 480 h per month. The analysis model of each activity trait
      included the effect of the average daily THI values below and above the
      determined heat load threshold and the effect of the daily heat load duration
      exceeding the determined heat load threshold. The total lying/standing time and
      the number of steps showed significant changes related to increasing daily heat
      load duration. The effect of the daily heat load duration additionally
      intensified the effect of the average daily THI.

PMID- 30196902
TI  - Low quality diet and challenging temperatures affect vital rates, but not thermal
      tolerance in a tropical insect expanding its diet to an exotic plant.
AB  - Determining responses of organisms to changing temperatures is a research
      priority, as global warming threatens populations and ecosystems worldwide. Upper
      thermal limits are frequently measured as the critical thermal maximum (CTmax), a
      quick bioassay where organisms are exposed to increasing temperatures until
      individuals are not able to perform basic motor activities such as walking or
      flying. A more informative approach to understand organism responses to global
      warming is to evaluate how vital rates, such as growth or survival, change with
      temperatures. The main objectives of this study are: (1) to determine if factors
      affecting insect vital rates such as diet quality, developmental temperatures or
      acclimation also affect CTmax and (2) to determine if vital rates of different
      life stages (i.e., insect larvae or adults) display different responses to
      temperature changes. If different life stages have particular thermal
      requirements, this may indicate different susceptibility to global warming. This
      study focuses on Cephaloleia belti (Coleoptera: Chrysomelidae), a tropical insect
      currently expanding its diet to an exotic host plant. We determined how high and
      low-quality diets (i.e., native vs novel host), as well as exposure temperatures
      affect CTmax of adult beetles. We also estimated larval and adult survival when
      feeding on high and low quality host plants, when exposed to temperatures typical
      of the elevational distribution of this species, or when exposed to projected
      temperatures in 100 years. We did not detect an effect of diet quality or
      acclimation on CTmax. However, larvae and adults had different thermal
      requirements. CTmax is not affected by previous diet or acclimation as an adult.
      We propose that to understand processes involved in the adaptation and
      persistence of ectotherm populations in a warming world, studies must explore
      responses beyond CTmax, and focus on the response of vital rates to changing
      temperatures.

PMID- 30196903
TI  - Small interfering RNA based knock down of acute heat shock and or GGA inducible
      bovine heat shock protein 70 may interfere invitro expression pattern of TLR2/4
      and NOD1/2.
AB  - Heat shock protein 70 (Hsp70) is a widely known mammalian stress-inducible
      protein critical for cytoprotection against different stressors. Despite the
      chaperone based cytoprotective functions, intracellular Hsp70 also participates
      in diverse immune modulatory activities. To investigate the immune modulatory
      effect of inducible bovine Hsp70, we examined the expression profile of four
      major pattern recognition receptors (PRRs) viz. TLR2/4 and NOD1/2 using two
      different invitro cell cultured models. We observed that, invitro acute heat
      stress and Geranylgeranylacetone (GGA) induction increased the level of Hsp70
      which upregulated the expression of all the four PRRs in both the cell cultured
      models. However, the expression level of TLR4 was found to be highest followed by
      NOD2, TLR2 and NOD1. Conversely, specific siRNA based knockdown of Hsp70 showed a
      decreased expression level of all the four PRRs. This study may add some
      references pertaining to the innate immune modulatory effects of bovine heat
      shock protein 70.

PMID- 30196904
TI  - Central cholinergic activation induces greater thermoregulatory and
      cardiovascular responses in spontaneously hypertensive than in normotensive rats.
AB  - There is evidence that central cholinergic stimulation increases heat dissipation
      in normotensive rats besides causing changes on the cardiovascular system via
      modulation of baroreceptors activity. However, the contribution of the central
      cholinergic system on thermoregulatory responses and its relationship with
      cardiovascular adjustments in spontaneously hypertensive rats (SHRs), an animal
      model of reduced baroreceptor sensitivity and thermoregulatory deficit, has not
      been completely clarified. Therefore, the aim of this study was to verify the
      involvement of the central cholinergic system in cardiovascular and
      thermoregulatory adjustments in SHRs. Male Wistar rats (n = 17) and SHRs (n = 17)
      were implanted with an intracerebroventricular cannula for injections of 2 uL of
      physostigmine (phy) or saline solution. Tail temperature (Ttail), internal body
      temperature (Tint), systolic arterial pressure (SAP), heart rate (HR) and
      metabolic rate were registered during 60 min while the animals remained at rest
      after randomly receiving the injections. The variability of the SAP and the HR
      was estimated by the fast Fourier transform. Phy treatment began a succession of
      cardiovascular and thermoregulatory responses that resulted in increased SAP,
      reduced HR and increased Ttail in both Wistar and SHRs groups. The magnitude of
      these effects seems to be more intense in SHRs, since the improvement of heat
      dissipation reflected in Tint. Taken together, these results provide evidence
      that hypertensive rats present greater cardiovascular and thermoregulatory
      responses than normotensive rats after central cholinergic stimulation.

PMID- 30196905
TI  - An altered Bioheat model for persons with cervical spinal cord injury.
AB  - The objective of this work is to develop a Bioheat model to predict the thermal
      responses of people with tetraplegia (TP) under hot, cold and neutral ambient
      conditions as well as different physical activities suitable for their level of
      injury. The focus is on TP with impairment or loss of motor and/or sensory
      function in C1 to C7 segments of the spinal cord due to damage of neural elements
      within the spinal canal. Starting from transient multi-segmented Bioheat model of
      able-bodied (AB) people, specific modifications were performed reflecting the
      changes in physiology due to the injury affecting the blood circulation system,
      energy expenditure, and thermoregulatory functions in the body. The TP Bioheat
      model predicts the TP thermal responses under steady and transient thermal
      conditions, and different activity levels that are appropriate for the level of
      injury. The model was validated with published experimental data reporting
      physiological and thermal data measurements on cases of people with complete and
      incomplete tetraplegia under controlled environmental conditions and activity
      levels. In both transient and steady state environmental conditions, the
      predicted core and mean skin temperature values were compared against the
      experimental data with maximum error of 0.86  degrees C and 0.9  degrees C
      respectively. The TP Bioheat model can be used as a tool to propose appropriate
      personal cooling strategies for TP.

PMID- 30196906
TI  - The changing scenario of 1st line therapy in non-oncogene addicted NSCLCs in the
      era of immunotherapy.
AB  - During the last two decades front-line treatment of metastatic Non Small Cell
      Lung Cancer (NSCLC) has profoundly changed moving from the old "one size fits
      all" concept to a "histology-based" approach and then, for a small subgroup of
      patients to a "molecularly-selected" one. The development of immune checkpoint
      inhibitors and the unprecedented results reported in 2nd/3rd line prompted the
      evaluation of these novel therapeutic agents in chemotherapy-naive patients
      either alone or in combination with platinum-based chemotherapy. Several
      randomized trials are evaluating the impact of immune-checkpoint inhibitors in
      1st line and some of them have yet produced preliminary evidence of efficacy.
      However, still a long way to go and several questions are still unanswered,
      including proper patients selection, optimal sequential/combinatorial use of
      these agents, appropriate treatment duration, and finally the identification of
      predictive biomarkers. The aim of this paper is to provide a comprehensive
      overview on the growing role of immune checkpoint inhibitors in the upfront
      treatment of advanced non-oncogene addicted NSCLC either as single agent or in
      combination with other agents.

PMID- 30196907
TI  - Biomarkers of response to immune checkpoint blockade in cancer treatment.
AB  - Immune checkpoint inhibitors (ICPis) are emerging as the new corner stone of
      cancer treatment due to their ability to produce durable responses in patients
      with various cancers. But, objective responses to ICPis vary among each type of
      cancer. Further, treatment with ICPis is often associated with risk of developing
      immune-related adverse event, which are potentially life-threatening if
      untreated, indicating a need for patient selection. However, given the complexity
      of the tumor microenvironment and the dynamic interaction between tumor and
      immune cells, development of robust biomarkers to predict patients who are likely
      to respond to treatment with ICPis remains a challenge. In this review we present
      an overview of the immune monitoring strategies that are currently in use to
      enable appropriate patient selection.

PMID- 30196908
TI  - Immuno-oncology in GI tumours: Clinical evidence and emerging trials of PD-1/PD
      L1 antagonists.
AB  - The use of immune checkpoint inhibitors constitutes an emerging therapeutic field
      for the therapy of gastrointestinal (GI) malignancies following the recent FDA
      approvals of PD-1 inhibitors for esophago-gastric adenocarcinoma, hepatocellular
      carcinoma and for microsatellite-instable tumors, which are mainly colorectal
      cancers. This paper reviews the clinical evidence end of 2017 and discusses the
      clinical development programs of atezolizumab, avelumab, durvalumab, nivolumab
      and pembrolizumab in GI-tract cancers. Since 2014, these antagonists of the PD
      1/PD-L1 axis have gained approval for use in numerous other tumors. Phase II
      trials and phase I expansion cohorts demonstrate clinical activity in patients
      with oesophageal, gastric, colorectal, anal and hepatic cancer. Signals of
      outstanding efficacy are particularly observed in biomarker selected populations
      and for certain combination regimen. Comprehensive phase III development programs
      have been initiated in oesophageal and gastric cancer, with randomized trials
      ongoing in hepatocellular and colorectal cancer as well.

PMID- 30196910
TI  - Evolution of randomized controlled trials and surrogacy of progression-free
      survival in advanced/metastatic urothelial cancer.
AB  - BACKGROUND: Clinical trials in advanced/metastatic urothelial cancer have been
      difficult to perform. We review the current characteristics of randomized
      controlled trials (RCTs) and evaluate whether PFS could be a potential surrogate
      endpoint for overall survival (OS) in advanced/metastatic urothelial cancer.
      METHODS: We identified trials by a systematic review of Medline, Embase, and the
      Cochrane Central Register of Controlled Trials from inception to April 2017. We
      included RCTs of patients with locally advanced/metastatic urothelial cancer that
      involved systemic therapy as an intervention, and those with reported hazards
      ratios (HRs) and corresponding 95% confidence intervals (CIs) for both OS and
      PFS, or provided Kaplan-Meier curves from which HRs and 95% CI could be
      calculated. The correlation coefficient between log of HRs for OS and PFS was
      calculated using linear regression weighted by sample size. RESULTS: Forty eight
      trials that enrolled 7019 patients were included in the review and 24 RCTs were
      included in the surrogacy analysis. 27(56.3%) of identified 48 RCTs were phase II
      trials, and the median sample size was 107(range, 30-626) for all RCTs. The
      correlation coefficient between log HR for PFS and log HR for OS was 0.79 (95%
      CI, 0.58-0.91). The correlation coefficient increased to 0.87 (95% CI, 0.72-0.94)
      after excluding the only trial with immune checkpoint inhibitor. Multiple
      sensitivity analyses did not change the results..aph."/> CONCLUSIONS: PFS is
      strongly correlated with OS in trials of advanced/metastatic urothelial cancer
      assessing the treatment benefit of new drugs And PFS warrants further exploration
      as a surrogate endpoint in clinical trial datasets.

PMID- 30196909
TI  - Early mortality in myeloma patients treated with first-generation novel agents
      thalidomide, lenalidomide, bortezomib at diagnosis: A pooled analysis.
AB  - INTRODUCTION: Early toxic death (<=60 days of diagnosis) in elderly multiple
      myeloma (MM) patients is attributable to active disease, age and co-morbidities.
      Rate of early toxic deaths is 10% with conventional chemotherapy mainly due to
      infection and renal failure. Novel agents have improved MM outcome at the expense
      of newer toxicity. METHODS: We analyzed 1146 individual patient data to assess
      toxic deaths during induction treatment with first-generation novel agents
      thalidomide, lenalidomide, bortezomib. RESULTS: During first-line therapy,
      119/1146 patients (10%) died for any cause, and 47/1146 (4%) due to toxicity,
      including 12/1146 (1%) early deaths. The 24-month cumulative incidence was 4.1%
      without any difference between bortezomib (18/503 patients, 4%) and lenalidomide
      (29/643patients, 5%; p = 0.31). Toxic deaths occurred in 34/1039 (3%) patients
      <80 years and 13/107 (12%) patients >=80 years. Causes were cardiac events (28%),
      infections (26%) and vascular complications (15%). In a multivariate analysis,
      older age and unfavorable ISS stage increased the risk of death. CONCLUSION:
      First-generation novel agents significantly reduced toxic deaths compared to
      conventional chemotherapy. One third of deaths during first-line therapy were due
      to cumulative drug-related toxicities, thus supportive approaches and prevention
      strategies should be optimized. The higher mortality rate for toxicity in
      octogenarians confirms the need for a careful frailty assessment.

PMID- 30196911
TI  - Role of vena cava filters for the management of cancer-related venous
      thromboembolism: Systematic review and meta-analysis.
AB  - BACKGROUND: Results from cohort studies evaluating the benefit in prevention of
      recurrent Venous Thromboembolism in cancer population are heterogeneous and
      controversial. OBJECTIVE: To determine the effectiveness and harms of vena cava
      filters alone or combined with anticoagulation to prevent the risk of recurrent
      venous thromboembolism in patients with cancer-related venous thromboembolism.
      MATERIALS AND METHODS: A search strategy was conducted in the MEDLINE, CENTRAL,
      EMBASE and LILACS databases. Searches were also conducted in other databases and
      unpublished literature. Clinical trials were included without language
      restrictions. The risk of bias was evaluated with the Cochrane Collaboration's
      tool and a modified version for cohort studies. An analysis of fixed effects was
      conducted. The primary outcome was recurrent venous thromboembolism. The
      secondary outcomes were overall survival and adverse effects. The measure of the
      effect was the risk ratio with a 95% confidence interval. RESULTS: Seven studies
      were included in the qualitative and quantitative analysis. 35,333 patients were
      found among the seven studies. A low risk of bias was shown for most of the study
      items. The overall risk ratio (RR) for recurrent venous thromboembolism was 2.53
      95%CI (1.35-4.75) favoring anticoagulation compared with vena cava filter.
      CONCLUSION: Vena cava filter did not show benefits for recurrent venous
      thromboembolism prevention in the cancer-patients population.

PMID- 30196912
TI  - GEORCC recommendations on target volumes in radiotherapy for Head Neck Cancer of
      Unkown Primary.
AB  - Head Neck Cancer of Unknown Primary (HNCUP) is a rare condition, representing
      approximately 5-10% of all head neck cancers. Radiotherapy, adjuvant or radical,
      is usually employed in the treatment of those patients. To date, no specific
      guidelines for the optimal definition of the target volume to be irradiated have
      been published. In recent years, there have been advances in the knowledge of the
      molecular biology of HNCUP, its diagnostic imaging and the implementation of
      sophisticated radiotherapy techniques with enhanced precision in target
      localization and treatment delivery. These progresses have provided valuable
      information about the natural history of HNCUP that will allow for establishment
      of the best treatment for each patient, including standardized, consistent and
      reproducible target volumes definitions. Several recommendations regarding how to
      choose volumes when contouring HNCUP in clinical practice are reported, in order
      to achieve a high rate of loco-regional control while avoiding unnecessary
      toxicity.

PMID- 30196913
TI  - A comprehensive review of the role of immune checkpoint inhibitors in brain
      metastasis of renal cell carcinoma origin.
AB  - The contribution of renal cell carcinoma (RCC) to brain metastases (BM) reaches 7
      13%. These patients have limited survival with local control and targeted
      therapies. Immune checkpoint inhibitors (ICI) revolutionized the treatment
      landscape of RCC but commonly excluded BM patients from their pivotal trials. The
      daily clinical practice often imposes the use of ICI in RCC patients with BM in
      view of the promising survival times and durations of response. Only small
      prospective trials have included BM patients but rarely reported on the efficacy
      or safety of ICI in this subgroup. The available data is limited to small
      retrospective and prospective series that have shown comparable efficacy to that
      of the pivotal trials. In this review, we will discuss the biological rationale
      and potential concerns for the use of ICI in BM RCC. Furthermore, we will
      summarize BM subgroup data from the prospective and retrospective series of ICI
      in RCC as well as the use of cranial radiation and ICI.

PMID- 30196915
TI  - Clinical update on K-Ras targeted therapy in gastrointestinal cancers.
AB  - KRAS mutations are common in pancreatic and colorectal cancers and are associated
      with lack of response to anti-epidermal growth factor receptor therapy. Ras is an
      established therapeutic target that has long eluded efforts to develop specific
      inhibitors, while targeting downstream signaling pathways has proven largely
      ineffective, highlighting a need for rational combination strategies to overcome
      resistance. Recently, renewed interest in directly targeting Ras has led to the
      development of several small-molecule inhibitors that bind directly to K-Ras or
      its effector proteins, downregulation of K-Ras expression using therapeutic
      antisense oligonucleotides or siRNAs, and targeting scaffold proteins such as
      kinase suppressor of Ras. Indirect approaches to inhibiting K-Ras include
      combining inhibitors of the mitogen-activated protein kinase pathway with novel
      targeted agents. Immunotherapy in early studies has also shown clinical promise.
      This review summarizes the current evidence for each of these approaches.

PMID- 30196914
TI  - The use of SAMe in chemotherapy-induced liver injury.
AB  - Drug-induced liver injury (DILI) remains the most common cause of acute liver
      failure in the Western world. Chemotherapy is one of the major class of drugs
      most frequently associated with idiosyncratic DILI. For this reason, patients who
      receive chemotherapy require careful assessment of liver function prior to
      treatment to determine which drugs may not be appropriate and which drug doses
      should be modified. S-adenosylmethionine (SAMe) is an endogenous agent derived
      from methionine. Its supplementation is effective in the treatment of liver
      disease, in particular intrahepatic cholestasis (IHC). The target of this review
      is to analyze the mechanisms of hepatotoxicity of the principal anticancer agents
      and the role of SAMe in the prevention of this complication.

PMID- 30196916
TI  - Trastuzumab uptake in HER2-positive breast cancer patients: a systematic review
      and meta-analysis of observational studies.
AB  - Overexpression of the HER2 gene is predictive of treatment benefit with
      trastuzumab therapy for breast cancer (BC) patients. The study objective was to
      investigate whether all eligible patients with HER2-positive BC initiated
      trastuzumab therapy. A systematic search was conducted through PubMed, Web of
      Science PsycINFO, Cumulative Index to Nursing and Allied Health Literature
      (CINAHL) and Cochrane Library. From 2651 studies identified, 107 observational
      studies were included for full text review, of which 26 met the inclusion
      criteria and an additional 7 studies were identified through citation searching.
      Two independent reviewers extracted data for accuracy and completeness. From 33
      observational studies, 14,644 patients were exposed to trastuzumab therapy. Age
      range varied across studies; the youngest cohort had a median age of 50 and the
      oldest had a median age of 84. Sample sizes ranged from 11 to 1928 and included
      patients from 10 countries. Studies were heterogenous and few studies accounted
      for confounders. We identified large variability in uptake of trastuzumab in HER2
      positive early BC patients (9.1-100%) and metastatic BC patients (50.8-84.0%).
      The pooled uptake was 71.3% (95% CI 64.6-77.9%), with high heterogeneity (I2 =
      99.05%). The most conservative predictors of higher uptake included younger age
      (OR 2.09; 95% CI 1.36-3.20) and lower Charlson Comorbidity Index of patients (OR
      1.62; 95% CI 1.32-1.99). In addition, tumour characteristics including higher
      tumour grade (OR 1.73; 95% CI 1.23-2.45), larger tumour size (OR 1.80; 95% CI
      1.54-2.10), advanced tumour stage (OR 2.07; 95% CI 1.44-2.96) and hormone
      receptor negative tumor (OR 1.54; 95% CI 1.35-1.77) were associated with higher
      uptake. The uptake of trastuzumab therapy varied widely between studies and
      across subgroups suggesting that there may be some inequalities in the use of
      this agent. However, our findings should be interpreted with caution due to study
      heterogeneity and potential confounding, and thus additional studies of
      individual level data which control for confounders are needed to understand more
      about inequalities in uptake.

PMID- 30196917
TI  - The toxic benthic dinoflagellate Prorocentrum maculosum Faust is a synonym of
      Prorocentrum hoffmannianum Faust.
AB  - Three strains of the toxic benthic dinoflagellate Prorocentrum hoffmannianum were
      isolated in the Canary Islands (north-east Atlantic Ocean, Spain). The identity
      of the strains was determined by phylogenetic analyses of partial LSU rDNA (D1-D2
      regions) but their morphology based on SEM images corresponded to P. maculosum.
      Their toxin profiles were analyzed by liquid chromatography and high resolution
      mass spectrometry analysis (LC-HRMS) on cell extracts and culture media. Okadaic
      acid and three analogs were detected in all strains. Rather, in culture media the
      detected compounds were variable among strains, two of them being okadaic acid
      analogs not found on cell extracts. As a result, the taxonomy of the species was
      revised and P. maculosum is proposed as a junior synonym of P. hoffmannianum
      whose description is emended.

PMID- 30196918
TI  - Differential feeding by common heterotrophic protists on 12 different Alexandrium
      species.
AB  - The genus Alexandrium often forms harmful algal blooms causing human illness and
      large-scale mortality of fish and shellfish. Thus, Alexandrium bloom dynamics are
      primary concerns for scientists, government officials, aquaculture farmers, and
      the public. To understand bloom dynamics, mortality due to predation needs to be
      assessed; however, interactions between many Alexandrium species and their
      potential predators have not previously been reported. Thus, feeding by five
      common heterotrophic dinoflagellates (Oxyrrhis marina, Gyrodinium dominans,
      Polykrikos kofoidii, Pfiesteria piscicida, and Oblea rotunda) and a naked ciliate
      (Strombidinopsis sp.) on 12 Alexandrium species was examined. Furthermore, the
      growth and ingestion rates of P. kofoidii on A. minutum CCMP 1888 (previously A.
      lusitanicum), A. minutum CCMP 113, and A. tamarense were measured as a function
      of prey concentration. The growth rates of P. kofoidii on the other Alexandrium
      species at single high prey concentrations were measured, at which the growth
      rates on A. minutum CCMP 1888 and A. tamarense were saturated. Feeding occurrence
      by these predators on 12 Alexandrium species could be categorized into 6
      different prey groups. Each Alexandrium species was consumed by at least one
      predator; however, there was no Alexandrium species that was eaten by all six
      predators. Cells of A. minutum CCMP 1888, A. minutum CCMP 113, and A. tamarense
      were fed upon by four predators, but A. affine and A. pacificum by only one
      predator species, P. kofoidii or Strombidinopsis sp. Furthermore, A. minutum CCMP
      1888 and A. tamarense supported high growth rates of P. kofoidii, but the other
      Alexandrium species did not support, but rather inhibited P. kofoidii growth.
      With increasing prey concentrations, the growth and ingestion rates of P.
      kofoidii on A. minutum CCMP 1888 and A. tamarense increased and became saturated,
      whereas those on A. minutum CCMP 113 continuously decreased. The maximum growth
      rates of P. kofoidii on A. tamarense and A. minutum CCMP 1888 were 1.010 and
      0.765 d-1, respectively, and P. kofoidii maximum ingestion rates were 26.2 and
      11.1 ng C predator-1d-1, respectively. In contrast, the growth rates of P.
      kofoidii on the other Alexandrium species at single high prey concentrations were
      almost zero (A. pacificum) or negative. Based on the feeding occurrence and
      growth and ingestion rates of predators on 12 Alexandrium species, it is
      suggested that common heterotrophic protistan predators respond differently to
      different Alexandrium species, and thus ecological niches of the Alexandrium
      species may be different from each other. These results may provide an insight
      into the roles of protistan predators in bloom dynamics of Alexandrium species.

PMID- 30196919
TI  - Environmental factors influencing the quantitative distribution of microcystin
      and common potentially toxigenic cyanobacteria in U.S. lakes and reservoirs.
AB  - Many species of cyanobacteria are capable of producing toxins and causing
      nuisance blooms, however response to environmental conditions is likely taxon
      specific. Environmental factors influencing cyanobacterial composition and toxin
      production in lakes have been examined in many studies; yet are often confined to
      individual water bodies, or to a small number of systems within the same region.
      Here, data from the 2012 USEPA National Lakes Assessment are used to examine
      relationships between biovolume of common potentially-toxigenic cyanobacteria
      (Aphanizomenon spp., Cylindrospermopsis spp., Dolichospermum spp., Microcystis
      spp. and Planktothrix spp.) and environmental variables across the entire
      conterminous United States, and results are compared across nine distinct
      ecoregions. Total phosphorus and water clarity were identified as the most
      influential environmental factors correlated with phytoplankton community
      composition. The Northern, Southern and Temperate Plains ecoregions displayed the
      highest biovolumes of potentially toxigenic taxa on average, as well as highest
      mean concentrations of microcystin. In those three ecoregions, samples with
      microcystin concentrations greater than 1 ppb were primarily dominated by
      Planktothrix spp. while in all other ecoregions Dolichospermum spp. was the
      dominant genus. Canonical Correlation Analysis revealed a strong association
      between high microcystin concentrations and high nutrient concentrations (total
      nitrogen and total phosphorus), and between high microcystin concentrations and
      low percentage of watershed forest cover. Results from this study indicate that
      the likely occurrence of potentially toxigenic taxa in lakes and reservoirs is
      predictable on a biogeographical basis, depending on morphological and water
      quality characteristics. Data from this study may be useful to regional managers
      attempting to prevent or mitigate nuisance cyanobacterial blooms.

PMID- 30196920
TI  - Diversity and toxicity of Pseudo-nitzschia species in Monterey Bay: Perspectives
      from targeted and adaptive sampling.
AB  - Monterey Bay, California experiences near-annual blooms of Pseudo-nitzschia that
      can affect marine animal health and the economy, including impacts to tourism and
      commercial/recreational fisheries. One species in particular, P. australis, has
      been implicated in the most toxic of events, however other species within the
      genus can contribute to widespread variability in community structure and
      associated toxicity across years. Current monitoring methods are limited in their
      spatial coverage as well as their ability to capture the full suite of species
      present, thereby hindering understanding of HAB events and limiting predictive
      accuracy. An integrated deployment of multiple in situ platforms, some with
      autonomous adaptive sampling capabilities, occurred during two divergent bloom
      years in the bay, and uncovered detailed aspects of population and toxicity
      dynamics. A bloom in 2013 was characterized by spatial differences in Pseudo
      nitzschia populations, with the low-toxin producer P. fraudulenta dominating the
      inshore community and toxic P. australis dominating the offshore community. An
      exceptionally toxic bloom in 2015 developed as a diverse Pseudo-nitzschia
      community abruptly transitioned into a bloom of highly toxic P. australis within
      the time frame of a week. Increases in cell density and proliferation coincided
      with strong upwelling of nutrients. High toxicity was driven by silicate
      limitation of the dense bloom. This temporal shift in species composition
      mirrored the shift observed further north in the California Current System off
      Oregon and Washington. The broad scope of sampling and unique platform
      capabilities employed during these studies revealed important patterns in bloom
      formation and persistence for Pseudo-nitzschia. Results underscore the benefit of
      expanded biological observing capabilities and targeted sampling methods to
      capture more comprehensive spatial and temporal scales for studying and
      predicting future events.

PMID- 30196921
TI  - Overvalued allelopathy and overlooked effects of humic acid-like substances on
      Microcystis aeruginosa and Scenedesmus obliquus competition.
AB  - To form Microcystis blooms, Microcystis must be competitively dominant to other
      phytoplankton species to produce enough biomass. The aim of this study was to
      determine the competition mechanisms between Microcystis aeruginosa and
      Scenedesmus obliquus. M. aeruginosa and S. obliquus were separately cultured in
      the filtrate of mono and mixed cultures of M. aeruginosa and S. obliquus with
      varying treatments concerning N, P and iron availability. The inhibition rate for
      M. aeruginosa was 20-31% when cultured in mono and mixed culture filtrates
      enriched with N and P, but this rate was reduced to -15 to 19% when cultured in
      filtrates enriched with N, P and iron. The inhibition rate for M. aeruginosa
      decreased from 80 to 100% to 11-39% in dialytic filtrates. However, there were no
      differences in inhibition rate for S. obliquus, regardless of filtrate or
      dialytic filtrate treatments. The potential allelochemical, 2-butyl-octanol
      (0.144 mg L-1), was found to have little inhibitory effect to M. aeruginosa or S.
      obliquus. Thus, previously reported allelopathy to Microcystis would be
      overestimated. We also report a new mechanism in phytoplankton competition in
      this study. The phytoplankton secreted humic acid-like substances that can reduce
      the bioavailability of iron, resulting in the inhibition of other phytoplankton.

PMID- 30196922
TI  - Seawater nitrogen concentration and light independently alter performance,
      growth, and resource allocation in the bloom-forming seaweeds Ulva lactuca and
      Ulvaria obscura (Chlorophyta).
AB  - Ulva lactuca and Ulvaria obscura are seaweeds that form green tides on Salish Sea
      shores. They have similar macroscopic morphologies but differ in their
      biochemistries and physiological responses. To understand how they are affected
      by changes in environmental conditions, a factorial experiment was conducted in
      which algae were grown in artificial seawater with either low (10 MUM) or high
      (160 MUM) nitrate (NO3-) concentrations at high (29 mol photons.m-2.day-1) and
      low (4 mol photons.m-2.day-1) light levels. Light and NO3- affected algal
      responses, but always independently. After two weeks, U. lactuca grown in high
      light were larger, had lower maximum quantum yields (MQYs), and lower nitrogen
      (N), carbon (C), pigment, and dimethylsulfoniopropionate (DMSP) concentrations,
      respectively, relative to algae in low light. In contrast, U. obscura growth was
      unaffected by light. Like U. lactuca, U. obscura grown in high light had lower
      MQYs, and N, pigment, and DMSP concentrations. In high light, U. obscura also had
      89% higher dopamine concentrations and a tendency to fragment. Both U. lactuca
      and U. obscura grown in 160 MUM NO3- were larger, had higher MQYs, and higher N,
      pigment, and DMSP concentrations, respectively, than algae in 10 MUM NO3-. Also,
      when U. obscura was grown in the 160 MUM NO3- medium, it significantly increased
      its surface area/mass ratio. Although both species grew faster in high NO3-, high
      light only promoted the growth of Ulva, which may explain the dominance of Ulva
      in summer months. High light was physiologically stressful to both species and
      caused increases in photoprotective mechanisms, such as the production of
      dopamine, a melanin precursor, in Ulvaria, and DMSP lysis in Ulva to generate
      antioxidants. Growing in 10 MUM NO3- produced responses that were consistent with
      nitrogen limitation and had greater impacts on Ulvaria than Ulva, suggesting that
      Ulvaria responds more strongly to eutrophication.

PMID- 30196923
TI  - The impact of short-term depositions of macroalgal blooms on widgeon-grass
      meadows in a river-dominated estuary.
AB  - Macroalgal blooms can trigger adverse biogeochemical conditions at the sediment
      water interface of shallow coastal areas, hence threatening critical habitats
      such as seagrasses meadows. The direction and magnitude of macroalgal blooms
      impacts on the aquatic ecosystem can be context-dependent, varying according to
      the local hydrodynamic conditions. Thus, studies investigating the impacts of
      stagnant algal depositions on the benthos may fail to address realistic
      situations and interactions which are common in well-flushed systems. This is
      especially true for the South America coast, where no study has investigated the
      effects of macroalgal blooms on seagrasses meadows. To fully understand the
      impacts of macroalgal blooms on sediment biogeochemistry and seagrass habitats
      across distinct environmental conditions and biogeographical regions, two
      independent, complementary field experiments replicated the natural temporal
      patterns of drift macroalgal mats depositions on unvegetated and vegetated
      (Ruppia maritima meadows) shoals of the Patos Lagoon estuary (PLE), a
      subtropical, high hydrodynamic system in southern Brazil. Transitory depositions
      of algal mats alleviated deleterious biogeochemical conditions in the sediment
      water interface of unvegetated bottoms. Nevertheless, these unstable algal
      depositions promoted significant reductions in R. maritima biomass, by reducing
      their shoot height and density, and rhizome length. That plant biomass reductions
      were followed by a decrease in the abundance of the dominant infaunal tanaidacean
      Monokalliapseudes schubarti, indicating that algal impacts on seagrasses were
      transferred to higher trophic levels. Our results suggest that, although unstable
      deposition of drift algal mats can attenuate potential adverse impacts at the
      sediment-water interface, the physical stress during mats advection can still
      trigger small seagrass losses. This process may diminish the resilience of R.
      maritima meadows in the PLE, with impacts on estuarine nutrient cycling and
      secondary production. We conclude that, although harmful drift macroalgal blooms
      area global phenomenon, the mechanisms through which macroalgae impair seagrass
      habitats may vary according to the environmental context. Therefore, further
      studies are necessary to identify the underlying mechanisms of drift macroalgae
      seagrass-macrofauna interactions in high hydrodynamic systems and their
      generality across distinct biogeographical areas.

PMID- 30196924
TI  - Microcystin interferes with defense against high oxidative stress in harmful
      cyanobacteria.
AB  - Harmful cyanobacteria producing toxic microcystins are a major concern in water
      quality management. In recent years, hydrogen peroxide (H2O2) has been
      successfully applied to suppress cyanobacterial blooms in lakes. Physiological
      studies, however, indicate that microcystin protects cyanobacteria against
      oxidative stress, suggesting that H2O2 addition might provide a selective
      advantage for microcystin-producing (toxic) strains. This study compares the
      response of a toxic Microcystis strain, its non-toxic mutant, and a naturally non
      toxic Microcystis strain to H2O2 addition representative of lake treatments. All
      three strains initially ceased growth upon H2O2 addition. Contrary to
      expectation, the non-toxic strain and non-toxic mutant rapidly degraded the added
      H2O2 and subsequently recovered, whereas the toxic strain did not degrade H2O2
      and did not recover. Experimental catalase addition enabled recovery of the toxic
      strain, demonstrating that rapid H2O2 degradation is indeed essential for
      cyanobacterial survival. Interestingly, prior to H2O2 addition, gene expression
      of a thioredoxin and peroxiredoxin was much lower in the toxic strain than in its
      non-toxic mutant. Thioredoxin and peroxiredoxin are both involved in H2O2
      degradation, and microcystin may potentially suppress their activity. These
      results show that microcystin-producing strains are less prepared for high levels
      of oxidative stress, and are therefore hit harder by H2O2 addition than non-toxic
      strains.

PMID- 30196925
TI  - Habitat complexity affects benthic harmful dinoflagellate assemblages in the
      fringing reef of Rawa Island, Malaysia.
AB  - Few studies have investigated the effect of fine-scale habitat differences on the
      dynamics of benthic harmful dinoflagellate assemblages. To determine how these
      microhabitat differences affect the distribution and abundance of the major
      benthic harmful dinoflagellate genera in a tropical coral reef ecosystem, a field
      study was undertaken between April-September 2015 and January 2016 on the shallow
      reef flat of the fringing reef of Rawa Island, Terengganu, Malaysia. Sampling of
      benthic dinoflagellates was carried out using an artificial substrate sampling
      method (fiberglass screens). Benthic microhabitats surrounding the sampling
      screens were characterized simultaneously from photographs of a 0.25-m2 quadrat
      based on categories of bottom substrate types. Five taxonomic groups of benthic
      dinoflagellates, Ostreopsis, Gambierdiscus, Prorocentrum, Amphidinium, and Coolia
      were identified, and cells were enumerated using a light microscope. The results
      showed Gambierdiscus was less abundant than other genera throughout the study
      period, with maximum abundance of 1.2 * 103 cells 100 cm-2. While most taxa were
      present on reefs with high coral cover, higher cell abundances were observed in
      reefs with high turf algal cover and coral rubble, with the exception of
      Ostreopsis, where the abundance reached a maximum of 3.4 * 104 cells 100 cm-2 in
      habitats with high coral cover. Microhabitat heterogeneity was identified as a
      key factor governing the benthic harmful dinoflagellate assemblages and may
      account for much of the observed variability in dominant taxa. This finding has
      significant implications for the role of variability in the benthic harmful algal
      bloom (BHAB) outbreaks and the potential in identifying BHAB-related toxin
      transfer pathways and the key vectors in the food webs.

PMID- 30196926
TI  - Insights into cyanophage-mediated dynamics of nodularin and other non-ribosomal
      peptides in Nodularia spumigena.
AB  - The effect of cyanophage infection and lysis on the dynamics of the hepatotoxin
      nodularin (NOD) and other non-ribosomal peptides (NRPs) produced by cyanobacteria
      is poorly understood. In this study, changes in concentration of NOD and other
      NRPs during cyanophage infection of the filamentous cyanobacteria Nodularia
      spumigena were assessed using incubation experiments. Viral infection and lysis
      were associated with a significant reduction (93% at the 96 h post infection) of
      N. spumigena cell density. While no correlation between N. spumigena abundance
      and total concentration of NOD (ng mL-1) within the infected cells was observed,
      cellular NOD quota (ng cell-1) gradually increased in the remaining cyanophage
      resistant N. spumigena subpopulation. Lysis of N. spumigena cells resulted in a
      substantial increase (>57 times) of dissolved NOD concentration in the culture
      medium. The relative concentration of other cyclic (anabaenopeptins) and linear
      (aeruginosins, spumigins) NRPs produced by N. spumigena also increased in
      response to cyanophage addition. This study highlights the importance of
      cyanophage infection on the population toxicity of filamentous cyanobacteria and
      demonstrates a significant contribution of virus-mediated cell lysis on the
      conversion of NOD from the particulate to dissolved phase.

PMID- 30196927
TI  - Sympatric occurrence of two Azadinium poporum ribotypes in the Eastern
      Mediterranean Sea.
AB  - The marine dinoflagellate Azadinium poporum produce azaspiracids (AZA) and has
      been recorded widely in the world. However, information on its biogeography is
      still limited, especially in view of the fact that A. poporum comprises several
      genetically differentiated groups. A total of 18 strains of A. poporum were
      obtained from the Eastern Mediterranean area by incubating surface sediment
      collected from Ionian Sea of Greece. The morphology of these strains was examined
      with light microscopy and scanning electron microscopy. Small subunit ribosomal
      DNA (SSU rDNA), large subunit ribosomal DNA (LSU rDNA) and internal transcribed
      spacer (ITS) sequences were obtained from all cultured strains. Molecular
      phylogeny based on concatenated SSU, LSU and ITS sequences confirmed three
      ribotypes within A. poporum and revealed two subclades within ribotypes A and C.
      Greek strains of A. poporum ribotype A were nested within ribotype A2 together
      with strains from Western Mediterranean Sea and French Atlantic, and Greek
      strains of A. poporum ribotype C were nested within ribotype C2 together with a
      strain from the Gulf of Mexico. Growth experiments on four selected strains
      revealed that ribotypes A and C from Greece differed in their growth at higher
      temperatures, indicating that they are physiologically differentiated.
      Azaspiracid profiles were analyzed for 15 cultured A. poporum strains using
      LCMS/MS and demonstrate that the A. poporum ribotype A from Greece produce low
      level or no AZA and A. poporum ribotype C from Greece produces predominantly AZA
      40 (9.6-30.2 fg cell-1) followed by AZA-2 (2.1-2.6 fg cell-1). The first record
      of AZA-40 producing A. poporum from the Mediterranean suggests that this species
      is a potential source for azaspiracid contaminations in shellfish from the
      Eastern Mediterranean Sea.

PMID- 30196928
TI  - Genetic evidence in tracking the origin of Ulva prolifera blooms in the Yellow
      Sea, China.
AB  - Recurrent green tides have been recorded in the Yellow Sea for 11 consecutive
      years. The origin of floating green algae in the Yellow Sea, however, remains a
      subject of debate. Previous studies suggest that the major bloom-forming green
      alga Ulva prolifera represent a unique ecotype different from other attached
      populations of U. prolifera in China. In this study, 97 green algal samples
      collected during the 2012 green-tide event and from other locations along the
      coastline of China were analyzed. Based on the sequences of nuclear ribosomal RNA
      gene (rDNA) internal transcribed spacer (ITS) region and 5S rDNA spacer region,
      the green alga U. prolifera in the samples were identified. The intraspecific
      genetic diversity within U. prolifera was then examined using sequences of 5S
      rDNA spacer and a marker of sequence characterized amplified region (SCAR) highly
      specific for bloom-forming U. prolifera in the Yellow Sea. The screening results
      for SCAR marker demonstrated that U. prolifera attached to aquaculture rafts in
      Subei Shoal belong to the same ecotype of the bloom-forming U. prolifera in the
      Yellow Sea. These findings offer genetic evidence that aquaculture rafts in Subei
      Shoal are a major source of floating green algae in the Yellow Sea.

PMID- 30196929
TI  - Effects of salinity variation on growth and yessotoxin composition in the marine
      dinoflagellate Lingulodinium polyedra from a Skagerrak fjord system (western
      Sweden).
AB  - The marine dinoflagellate Lingulodinium polyedra is a toxigenic species capable
      of forming high magnitude and occasionally harmful algal blooms (HABs),
      particularly in temperate coastal waters throughout the world. Three cultured
      isolates of L. polyedra from a fjord system on the Skagerrak coast of Sweden were
      analyzed for their growth characteristics and to determine the effects of a
      strong salinity gradient on toxin cell quotas and composition. The cell quota of
      yessotoxin (YTX) analogs, as determined by liquid chromatography coupled with
      tandem mass spectrometry (LC-MS/MS), ranged widely among strains. For two
      strains, the total toxin content remained constant over time in culture, but for
      the third strain, the YTX cell quota significantly decreased (by 32%) during
      stationary growth phase. The toxin profiles of the three strains differed
      markedly and none produced YTX. The analog 41a-homo-YTX (m/z 1155), its putative
      methylated derivative 9-Me-41a-homo-YTX (m/z 1169) and an unspecified keto-YTX
      (m/z 1047) were detected in strain LP29-10H, whereas strain LP30-7B contained nor
      YTX (m/z 1101), and two unspecified YTX analogs at m/z 1159 and m/z 1061. The
      toxin profile of strain LP30-8D comprised two unspecified YTX analogs at m/z 1061
      and m/z 991 and carboxy-YTX (m/z 1173). Strain LP30-7B cultured at multiple
      salinities (10, 16, 22, 28 and 34) did not tolerate the lowest salinity (10), but
      there was a statistically significant decrease (by 21%) in toxin cell quota
      between growth at the highest versus lower permissible salinities. The toxin
      profile for strain LP30-7B remained constant over time for a given salinity. At
      lower salinities, however, the proportion of the unspecified YTX analog (m/z
      1061) was significantly higher, especially with respect to nor-YTX (m/z 1101).
      This study shows high intra-specific variability in yessotoxin composition among
      strains from the same geographical region and inconsistency in toxin cell quota
      under different environmental regimes and growth stages in culture. This
      variation has important implications for the kinetics of YTX production and food
      web transfer in natural bloom populations from diverse geographical regions.

PMID- 30196931
TI  - Nigeria: respiratory health in Africa's most populous nation.

PMID- 30196930
TI  - Effect of ciliate strain, size, and nutritional content on the growth and
      toxicity of mixotrophic Dinophysis acuminata.
AB  - Previous studies indicate differences in bloom magnitude and toxicity between
      regional populations, and more recently, between geographical isolates of
      Dinophysis acuminata; however, the factors driving differences in
      toxicity/toxigenicity between regions/strains have not yet been fully elucidated.
      Here, the roles of prey strains (i.e., geographical isolates) and their
      associated attributes (i.e., biovolume and nutritional content) were investigated
      in the context of growth and production of toxins as a possible explanation for
      regional variation in toxicity of D. acuminata. The mixotrophic dinoflagellate,
      D. acuminata, isolated from NE North America (MA, U.S.) was offered a matrix of
      prey lines in a full factorial design, 1 * 2 * 3; one dinoflagellate strain was
      fed one of two ciliates, Mesodinium rubrum, isolated from coastal regions of
      Japan or Spain, which were grown on one of three cryptophytes
      (Teleaulax/Geminigera clade) isolated from Japan, Spain, or the northeastern USA.
      Additionally, predator: prey ratios were manipulated to explore effects of the
      prey's total biovolume on Dinophysis growth or toxin production. These studies
      revealed that the biovolume and nutritional status of the two ciliates, and less
      so the cryptophytes, impacted the growth, ingestion rate, and maximum biomass of
      D. acuminata. The predator's consumption of the larger, more nutritious prey
      resulted in an elevated growth rate, greater biomass, and increased toxin quotas
      and total toxin per mL of culture. Grazing on the smaller, less nutritious prey,
      led to fewer cells in the culture but relatively more toxin exuded from the cells
      on per cell basis. Once the predator: prey ratios were altered so that an equal
      biovolume of each ciliate was delivered, the effect of ciliate size was lost,
      suggesting the predator can compensate for reduced nutrition in the smaller prey
      item by increasing grazing. While significant ciliate-induced effects were
      observed on growth and toxin metrics, no major shifts in toxin profile or
      intracellular toxin quotas were observed that could explain the large regional
      variations observed between geographical populations of this species.

PMID- 30196932
TI  - Usefulness of Serial 12-Lead Electrocardiograms in Predicting 30-Day Outcomes in
      Patients With Undifferentiated Chest Pain (the ASAP CATH Study).
AB  - An initial electrocardiogram (ECG) and serial troponin measurements are both
      independently and incrementally predictive of acute coronary syndrome in patients
      presenting with undifferentiated chest pain in the Emergency Department (ED).
      However, it is unclear if serial (ECGs) add significant to the contemporary
      diagnostic evaluation of this patient group. The ASAP CATH study was a single
      center, prospective study that enrolled patients presenting to an ED with
      undifferentiated chest pain. In addition to standard clinical evaluation, serial
      ECGs were performed at 90-minute intervals to evaluate whether serial changes
      suggestive of ischemia developed (Q waves, ST elevation or depression, or T-wave
      inversion). Total 365 subjects were enrolled from March 2014 to May 2015. Serial
      ECG changes developed in 6.6% (n = 24 of 365), the most common being the
      development of T-wave inversion (66.7%, n = 16 of 24). The sensitivity and
      positive predictive value of serial ECG changes were poor (<30%), with a less
      areas under the curve (0.55) compared with serial troponins alone (0.83). The
      addition of serial ECG changes to Thrombolysis In Myocardial Infarction risk
      scoring showed a decrease in the net reclassification index for major adverse
      cardiovascular events (-0.04, p <0.1) and was not significant for the prediction
      of major adverse cardiovascular events and/or acute coronary syndrome in 30 days
      (-0.003, p = 0.94). In conclusion, routine serial ECG evaluation for patients
      presenting with undifferentiated chest pain in the ED may not significantly
      improved diagnostic prognosis beyond current standard evaluation modalities.

PMID- 30196933
TI  - [We have to stop talking about "non compliant" patients but rather about patients
      with difficulties of medication adherence].
AB  - Medication adherence can be defined as the link between "what the patient
      implements" and "what the patient and his doctor have decided together after
      negotiating without constrains". This definition should be put into perspective
      with the chronology of the disease and the way the patient experiences it.
      Counselling actions should always be adapted to the situation and negotiated with
      the patient, all along the process of care. This article proposes a model for
      this process and offers options pour tailored counselling. Key elements for
      pharmacist's practice are: simplify the prescription; communicate with the
      patient according to his stage of acceptation of the disease; get adequate
      training for motivational interviewing.

PMID- 30196934
TI  - Cancer epidemiology update, following the 2011 IARC evaluation of radiofrequency
      electromagnetic fields (Monograph 102).
AB  - Epidemiology studies (case-control, cohort, time trend and case studies)
      published since the International Agency for Research on Cancer (IARC) 2011
      categorization of radiofrequency radiation (RFR) from mobile phones and other
      wireless devices as a possible human carcinogen (Group 2B) are reviewed and
      summarized. Glioma is an important human cancer found to be associated with RFR
      in 9 case-control studies conducted in Sweden and France, as well as in some
      other countries. Increasing glioma incidence trends have been reported in the UK
      and other countries. Non-malignant endpoints linked include acoustic neuroma
      (vestibular Schwannoma) and meningioma. Because they allow more detailed
      consideration of exposure, case-control studies can be superior to cohort studies
      or other methods in evaluating potential risks for brain cancer. When considered
      with recent animal experimental evidence, the recent epidemiological studies
      strengthen and support the conclusion that RFR should be categorized as
      carcinogenic to humans (IARC Group 1). Opportunistic epidemiological studies are
      proposed that can be carried out through cross-sectional analyses of high,
      medium, and low mobile phone users with respect to hearing, vision, memory,
      reaction time, and other indicators that can easily be assessed through
      standardized computer-based tests. As exposure data are not uniformly available,
      billing records should be used whenever available to corroborate reported
      exposures.

PMID- 30196935
TI  - Economic Burden of Veno-occlusive Disease in Patients With B-cell Acute
      Lymphoblastic Leukemia in the United States.
AB  - PURPOSE: The goal of this study was to evaluate the incidence, inpatient
      mortality, and economic burden of hepatic veno-occlusive disease (VOD) in adults
      with B-cell acute lymphoblastic leukemia (ALL) in the United States. METHODS:
      Using MarketScan Commercial Claims and Encounters Database and Medicare
      Supplemental and Coordination of Benefits Database, data for patients with B-cell
      ALL from April 1, 2009, to October 31, 2016, were extracted by using diagnosis
      codes. VOD was identified based on clinical criteria and expert opinions.
      Patients with VOD were followed up from diagnosis of VOD until the earliest
      occurrence of inpatient death, end of continuous enrollment, end of study period,
      or for a maximum of 100days. The incidence of VOD and VOD-associated inpatient
      mortality were calculated. VOD-related health care costs based on paid
      adjudicated claims were calculated. FINDINGS: Of the 2571 adults with B-cell ALL,
      the overall incidence of VOD was low at 3.4% (88 of 2571). Of these patients with
      VOD, 52% (46 of 88) experienced multiorgan failure and were identified as having
      severe VOD. VOD was only identified in patients having undergone hematopoietic
      stem cell transplantation (5.4% [88 of 1624]). The inpatient mortality rate of
      those with any VOD over the 100-day postindex period was 26.1%, and the inpatient
      mortality was even higher for patients with severe VOD (37.0%). Total mean (SD)
      medical costs per patient during the 100 days' post-VOD diagnosis were $55,975
      ($160,335); mean (SD) costs per patient were ~4-fold higher for severe ($86,953
      [$206,906]) versus nonsevere ($22,047 [$72,847]) VOD. IMPLICATIONS: Clinical
      criteria were used to identify VOD events and thus VOD might be underdiagnosed.
      The mortality of VOD also might be underestimated because only inpatient deaths
      are captured in the data. The incidence and mortality of VOD could also be
      underestimated because we focused on adult patients who might receive reduced
      intensity treatment. The economic burden of VOD may be underestimated because the
      Healthcare Common Procedure Coding System code specific for defibrotide was not
      available, and thus the cost for defibrotide might not be included. Finally, as
      the study population consisted of patients with commercial or Medicare
      supplemental insurance, results may not be generalizable to all patients with VOD
      in the United States. Although VOD occurred infrequently in adults with B-cell
      ALL, it was associated with high inpatient mortality and substantial costs.
      Patients with severe VOD were associated with highest mortality and highest
      costs. Given the clinical and economic burden associated with VOD, it is
      important that patients at high risk for VOD be identified and treated to
      minimize this risk.

PMID- 30196936
TI  - The Who, What, and Why of Drug Discovery and Development.
AB  - Inquiry into declining pharmaceutical R&D efficiency has focussed on 'what' can
      be improved, with only brief thought given to 'who' can be improved. Here, we
      argue that enabling people in the idea-to-product chain to have a more holistic
      knowledge of the behaviours and incentives of each other can optimise R&D.

PMID- 30196937
TI  - Introduction: Impact of nutrition on reproduction: an overview.
AB  - This Views and Reviews explores existing data regarding the impact of nutrition,
      supplements, and lifestyle changes as they relate to weight on the fertility of
      both men and women. Challenges and shortcomings in developing and performing well
      designed studies of nutrition and fertility are reviewed in these five papers,
      and the best evidence is presented. Recommendations are made based on the data,
      such as they are. It appears that folic acid supplementation above the level used
      by women to reduce the risk of neural tube defects may be of value in producing
      favorable pregnancy outcomes. Certain polyunsaturated fatty acids may have a
      beneficial effect on fertility, and a Mediterranean diet may prove advantageous
      in both men and women. Data do not consistently support a beneficial effect of
      vitamin D on reproduction, and caffeine use has not been shown to have a
      deleterious effect. Alcohol use may negatively impact reproductive success, and
      smoking appears to have a clearly negative impact in both men and women. Present
      data consistently show that obesity is associated with reduced reproductive
      efficiency in both women and men, but the data do not confirm that weight loss
      proximate to attempts at conception will reverse this effect. We would do well to
      appreciate that the ongoing state of being obese appears to be more relevant to
      reproduction than changing the obese state.

PMID- 30196938
TI  - Diet and female fertility: doctor, what should I eat?
AB  - Fecundity is the capacity to produce offspring. Identifying dietary factors that
      influence human fecundity is of major clinical and public health significance.
      This review focuses on the evidence from epidemiologic literature for the
      relationships between key nutritional factors and female reproductive potential.
      According to existing data, women trying to achieve pregnancy are encouraged to
      increase consumption of whole grains, omega-3 fatty acids, fish, and soy and to
      reduce consumption of trans fats and red meat. In addition, a daily multivitamin
      that contains folic acid before and during pregnancy may not only prevent birth
      defects, but also improve the chance of achieving and maintaining a pregnancy. In
      contrast, there is limited evidence supporting an association between vitamin D
      and human fecundity outcomes despite promising evidence from nonhuman studies.
      Questions for future research included the roles of other types of fat
      (especially omega-6 and monounsaturated fats) and protein (especially white meat
      and seafood) on female fertility; particular attention should also be paid to
      exposure to environmental contaminants in foods. Although much work remains, this
      review accrued best available evidence to provide practical dietary
      recommendations for women trying to conceive.

PMID- 30196939
TI  - Diet and men's fertility: does diet affect sperm quality?
AB  - Male contribution to a couple's fecundity is important, and identifying the
      dietary factors that can influence male fertility potential is of high
      importance. Despite this importance, there are currently no clear clinical
      guidelines for male patients seeking fertility treatment. In this review, we
      present the most up-to-date evidence about diet and male fertility in humans. We
      focus on the dietary factors necessary for production of healthy functioning
      sperm with high fertility potential. Based on this review, men may be encouraged
      to use antioxidant supplements and to follow dietary patterns favoring the
      consumption of seafood, poultry, nuts, whole grains, fruits, and vegetables.
      Evidence is strongest for recommending the use of antioxidant supplements to men
      in couples undergoing infertility treatment-although the specific antioxidants
      and doses remain unclear-and increasing consumption of omega-3 fatty acids from
      fish and nuts.

PMID- 30196940
TI  - Antioxidants in fertility: impact on male and female reproductive outcomes.
AB  - A couple may be considered to have fertility problems if they have been trying to
      conceive for over 1 year with no success. Worldwide, the inability to have
      children affects 10% to 15% of all couples. Subfertility can be divided into
      either male or female factor, or both partners can be affected. However, for some
      couples the cause for subfertility cannot be identified, and this is called
      unexplained subfertility. It is thought that oxidative stress is involved in the
      pathophysiology of subfertility, and antioxidants are thought to reduce the
      damage caused by oxidative stress. Antioxidants are widely available and
      inexpensive. However, there is currently little high-quality evidence to show
      that taking antioxidants will provide any benefit or harm for infertile couples.

PMID- 30196941
TI  - Successful weight loss interventions before in vitro fertilization: fat chance?
AB  - Most expert opinions and guidelines indicate the necessity for weight loss before
      in vitro fertilization (IVF) in women who are overweight or obese. This is based
      on the documented impact of obesity on pregnancy rates and pregnancy
      complications and the long-term impact on the child in natural conceptions. Some
      clinicians and authorities refuse to treat patients unless they are below a
      certain body mass index. In the past this advice has been hindered by a lack of
      opportunity for patients to join lifestyle programs and the high dropout failure
      before treatment. However, the ideal has remained in the search for effective
      methods for weight loss. New clinical trials have evaluated a lifestyle program
      before IVF treatment and compared the results with those who were merely given
      advice and allowed to proceed directly to other fertility treatments or IVF. No
      compelling evidence of the value of lifestyle intervention for weight loss on
      live-birth rates was gained from these well-conducted studies. The research and
      medical and ethical opinions may now favor moving to fertility treatment earlier
      than originally recommended for patients who are overweight or obese.

PMID- 30196942
TI  - Caffeine, alcohol, smoking, and reproductive outcomes among couples undergoing
      assisted reproductive technology treatments.
AB  - During the past decade, as the use of assisted reproductive technologies (ART)
      has continued to increase worldwide, research investigating whether modifiable
      lifestyle factors, such as alcohol, caffeine, and smoking, may affect ART
      outcomes has grown. Despite the vast literature, there is still uncertainty
      regarding the effects of some of these exposures on ART outcomes. The objective
      of this review is to summarize the epidemiologic literature on intakes of
      caffeine and alcohol, smoking, and reproductive outcomes among women undergoing
      ART. Of the five epidemiologic studies on caffeine intake and ART outcomes, only
      one found a significant negative effect of caffeine intake on live birth
      following ART. There have been six epidemiologic studies exploring whether
      alcohol intake is associated with fertility outcomes among women undergoing ART.
      Three studies assessed current alcohol consumption and observed a negative effect
      on outcomes such as fertilization, embryo quality, and implantation. When alcohol
      intake in the year before treatment was assessed, no relationships were observed
      with clinical outcomes following ART. Finally, numerous epidemiologic studies and
      a handful of meta-analyses have confirmed that female current smokers have worse
      ART outcomes compared with nonsmokers. Although former smokers tend to have
      better ART outcomes than current smokers, very few individual studies have
      investigated the influence of smoking cessation on ART outcomes. Literature on
      male smoking, drinking, and caffeine habits in relation to ART outcomes is even
      sparser and inconsistent, making it difficult to draw strong conclusions on that
      topic. In summary, there is little evidence supporting a detrimental effect of
      moderate caffeine intake on ART outcomes. Current consumption of alcohol may have
      a negative effect on ART outcomes, but at present the evidence is limited. Women
      who currently smoke cigarettes have been consistently found to have poorer ART
      outcomes, including reduced live birth rates, but a quantification of the
      benefits of smoking cessation is lacking.

PMID- 30196943
TI  - Liver injury and ulipristal acetate: an overstated tragedy?

PMID- 30196944
TI  - Association of childhood obesity with female infertility in adulthood: a 25-year
      follow-up study.
AB  - OBJECTIVE: To evaluate whether childhood obesity is associated with infertility
      in women's reproductive-aged life. DESIGN: Prospective longitudinal study.
      SETTING: Not applicable. INTERVENTION(S): None. PATIENT(S): A total of 1,544
      girls, aged 7-15 years in 1985, and who completed questionnaires at follow-up in
      2004-2006 and/or 2009-2011. MAIN OUTCOME MEASURE(S): Infertility was defined as
      having difficulty conceiving (had tried for >=12 months to become pregnant
      without succeeding) or having seen a doctor because of trouble becoming pregnant.
      RESULT(S): At ages from 7-11 years, girls at both the lower and upper end of the
      body mass index (BMI) z score had increased risk of infertility. Compared with
      normal weight girls, those with obesity at ages 7-11 years were more likely in
      adulthood to report infertility (adjusted relative risk [aRR] = 2.94, 95%
      confidence interval [CI] 1.48-5.84), difficulty conceiving (aRR = 3.89, 95% CI
      1.95-7.77), or having seen a doctor because of trouble becoming pregnant (aRR =
      3.65, 95% CI 1.90-7.02) after adjusting for childhood age, follow-up length,
      highest parental education, and marital status. CONCLUSION(S): Childhood obesity
      before 12 years of age appears to increase the risk of female infertility in
      later life.

PMID- 30196945
TI  - American Society for Reproductive Medicine position statement on uterus
      transplantation: a committee opinion.
AB  - Following the birth of the first child from a transplanted uterus in Gothenburg,
      Sweden, in 2014, other centers worldwide have produced scientific reports of
      successful uterus transplantation, as well as more recent media reports of
      successful births. The American Society for Reproductive Medicine recognizes
      uterus transplantation as the first successful medical treatment of absolute
      uterus factor infertility, while cautioning health professionals, patient
      advocacy groups, and the public about its highly experimental nature.

PMID- 30196946
TI  - Smoking and infertility: a committee opinion.
AB  - Approximately 21% of women of reproductive age and 22% of men of reproductive age
      in the United States smoke cigarettes. Substantial harmful effects of cigarette
      smoke on fecundity and reproduction have become apparent but are not generally
      appreciated. This committee opinion reviews the potential deleterious effects of
      smoking on conception, ovarian follicular dynamics, sperm parameters, gamete
      mutations, early pregnancy, and assisted reproductive technology (ART) outcomes.
      It also reviews the current status of smoking cessation strategies. This document
      replaces the 2012 ASRM Practice Committee document of the same name (Fertil
      Steril 2012;98:1400-6).

PMID- 30196947
TI  - Ethical obligations in fertility treatment when intimate partners withhold
      information from each other: an Ethics Committee opinion.
AB  - Clinicians should encourage disclosure between intimate partners but must
      maintain confidentiality in cases where there is no prospect of harm to the
      partner and/or offspring. In cases where one member of a couple refuses to
      disclose relevant health information to the other partner and there exists a risk
      of harm to the unaware partner and/or offspring, clinicians may refuse to offer
      care and should decline to treat if full informed consent is not possible due to
      lack of disclosure.

PMID- 30196948
TI  - Disclosure of sex when incidentally revealed as part of preimplantation genetic
      testing (PGT): an Ethics Committee opinion.
AB  - Clinics may develop a policy to disallow selecting which embryos to transfer
      based on sex and choose to use only embryo quality as selection criteria. Clinics
      may also develop a policy to use randomization to select those embryos for
      transfer if more embryos suitable for transfer are available than can be
      transferred.

PMID- 30196949
TI  - Importance of studying infertility from a life course perspective.

PMID- 30196950
TI  - Non-obstructive azoospermia and shortened leukocyte telomere length: further
      evidence linking poor health and infertility.

PMID- 30196951
TI  - With a good quality blastocyst, single embryo transfer remains the best choice.

PMID- 30196952
TI  - Are too many eggs truly too many?

PMID- 30196953
TI  - Trying to define the optimal progesterone elevation cut-off in fresh in vitro
      fertilization cycles: time to evolve our way of thinking.

PMID- 30196954
TI  - Programmed versus natural frozen embryo transfer: which is the best nest?

PMID- 30196955
TI  - Let's rescue oocytes: in vitro maturation 2.0 is coming.

PMID- 30196956
TI  - Identifying at-risk populations: are we simply not doing enough fertility
      preservation procedures?

PMID- 30196957
TI  - Hysterosalpingography and fertility: a technical relationship.

PMID- 30196958
TI  - Revisiting the relationship between vitamin D and ovarian reserve.

PMID- 30196959
TI  - Toxic pelvic cavity in endometriosis, a new frontier for medical therapies.

PMID- 30196960
TI  - True, true, and unrelated: tubal patency, tubal architecture, and tubal function.
AB  - "To understand the actual world as it is, not as we should wish it to be, is the
      beginning of wisdom." - Bertrand Russell.

PMID- 30196961
TI  - Shorter leukocyte telomere length is associated with risk of nonobstructive
      azoospermia.
AB  - OBJECTIVE: To determine the association between leukocyte telomere length and the
      risk of nonobstructive azoospermia (NOA). DESIGN: The mean leukocyte telomere
      length (LTL) among men with NOA, obstructive azoospermia (OA), and normospermic
      subjects was determined by quantitative polymerase chain reaction (PCR). We used
      logistic regression to investigate the association between LTL and the risk of
      NOA after adjustment for age and body mass index (BMI). Partial correlation
      analysis was also used to evaluate the relationship of clinical parameters with
      the mean LTL among men with OA and NOA. SETTING: Reproductive medicine center.
      PATIENTS(S): A total of 866 men, including 270 normospermic controls, 247 OA and
      349 NOA patients. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Leukocyte
      telomere length. RESULT(S): The mean relative LTL of men with NOA was
      significantly shorter than that of those with OA and in normospermic controls
      (odds ratio [OR] 0.81, 95% confidence interval [CI] 0.64-0.98 vs. OR 0.92, 95% CI
      0.70-1.24 vs. OR 0.99, 95% CI 0.83-1.22), respectively). Subjects with shorter
      telomeres (lowest tertile) had a significantly higher risk of NOA than those with
      longer telomeres (highest tertile). Interestingly, we also found that a low
      relative LTL was associated with poor efficiency of spermatogenesis using the
      Johnsen score after testis biopsy and histopathology in azoospermic patients,
      after adjusting for patient age and BMI. CONCLUSION(S): This is the first report
      that short LTL is associated with NOA, shedding light on an important biological
      pathway involved in the etiology of this form of male factor infertility.

PMID- 30196962
TI  - Effect of transfer of a poor quality embryo along with a top quality embryo on
      the outcome during fresh and frozen in vitro fertilization cycles.
AB  - OBJECTIVE: To evaluate the impact of a poor quality embryo (PQE) during double ET
      (DET) with a top quality embryo (TQE) on IVF outcome. DESIGN: A review of
      prospectively collected data. SETTING: Tertiary level fertility clinic.
      PATIENT(S): All patients undergoing blastocyst transfers as part of fresh IVF (n
      = 939) and frozen ET (n = 1,009) cycles performed between 2010 and 2016.
      INTERVENTION(S): Single ET (SET) with TQE (group 1) was set as control and
      compared with outcomes for SET with PQE (group 2), DET with 2 TQEs (group 3), PQE
      plus TQE (group 4), and 2 PQE (group 5). MAIN OUTCOME MEASURE(S): Live births and
      multiple births. RESULT(S): The live birth rates for group 4 were statistically
      similar to group 1 during fresh IVF (26.5% vs. 33.7%; odds ratio [OR], 0.95; 95%
      confidence interval [CI] 0.53-1.7) and frozen ET (24.2% vs. 32.7%; OR, 0.75; 95%
      CI 0.48-1.2), although there was a trend for lower success. Conversely, multiple
      births were higher in group 4 for fresh IVF (19% vs. 4.7%; OR, 2.9; 95% CI 1.3
      6.6) and frozen ET (10.3% vs. 2.6%; OR, 2.4; 95% CI 1.2-4.9). The live birth
      rates for group 2 (12.2% for fresh IVF and 14.6% for frozen ET) and group 5
      (21.2% for fresh IVF and 14% for frozen ET) were lower and for group 3 were
      higher (40.8% for fresh IVF and 40.3% for frozen ET) when compared with group 1.
      Multiple births were significantly higher with DET. CONCLUSION(S): This study
      does not support DET with one PQE along with a TQE, when there is only one TQE
      and one or more PQEs available for fresh IVF or frozen ET.

PMID- 30196963
TI  - Cumulative live birth rates according to the number of oocytes retrieved after
      the first ovarian stimulation for in vitro fertilization/intracytoplasmic sperm
      injection: a multicenter multinational analysis including ~15,000 women.
AB  - OBJECTIVE: To evaluate the association between the number of oocytes retrieved
      and cumulative live birth rates. DESIGN: Retrospective multicenter analysis using
      individual patient data. SETTING: Tertiary referral hospitals. PATIENT(S): In
      total, 14,469 patients were analyzed. The study included the first cycle of
      patients stimulated for IVF/intracytoplasmic sperm injection (ICSI) from 2009 to
      2014. All patients included in the analysis had either delivered a baby or had
      used all their embryos after their first stimulated cycle. All patients had
      vitrification as cryopreservation method. All women were followed up for at least
      2 years. INTERVENTION(S): Ovarian stimulation with GnRH antagonist protocol for
      IVF/ICSI. MAIN OUTCOME MEASURE(S): The primary outcome was the cumulative live
      birth rate defined as the delivery of at least one live-born infant (>24 weeks of
      gestation) in the fresh or in the subsequent frozen-thawed cycles in relation to
      the number of oocytes retrieved. Only the first delivery was considered in the
      analysis. The secondary outcome was live birth after the fresh IVF/ICSI cycle
      only. RESULT(S): Cumulative live birth rates steadily increased with the number
      of oocytes, reaching 70% when >=25 oocytes were retrieved. Interestingly, no
      plateau in cumulative live birth rates was observed, but a moderate increase of
      5.1% on average was detected beyond 27 oocytes. Regarding the fresh cycle
      outcome, live birth probability increased up to seven oocytes retrieved and
      remained relatively unchanged (increase or decrease of <=5%) between seven and 20
      oocytes retrieved. However, a drop in fresh live birth rates was identified
      thereafter, which could be attributed to the progressive increase in "freeze-all"
      cycle rate with the number of oocytes retrieved, exceeding 20% in patients with
      >20 oocytes retrieved. CONCLUSION(S): This is the largest multicenter study
      evaluating for the first time the impact of ovarian response on cumulative live
      birth rate. The significant progressive increase of cumulative live birth rate
      with the number of oocytes in our study suggests that ovarian stimulation may not
      have a detrimental effect on oocyte/embryo quality in good-prognosis women less
      than 40 year old. Nevertheless, although very high ovarian response may further
      increase cumulative live birth rates, ovarian stimulation should be rational and
      avoid extreme response in terms of oocytes retrieved to preserve patients'
      convenience and safety and avoid ovarian hyperstimulation syndrome or other
      iatrogenic complications.

PMID- 30196964
TI  - Defining thresholds for abnormal premature progesterone levels during ovarian
      stimulation for assisted reproduction technologies.
AB  - OBJECTIVE: To evaluate methodologies to establish abnormal progesterone (P)
      levels on the day of trigger for recommending freeze only cycles. DESIGN:
      Threshold analysis and cost analysis. SETTING: Private ART practice. PATIENT(S):
      Fresh autologous ART. INTERVENTIONS(S): None. MAIN OUTCOME MEASURE(S): Live
      birth. RESULT(S): Fourteen established statistical methodologies for generating
      clinical thresholds were evaluated. These methods were applied to 7,608 fresh ART
      transfer cycles to generate various P thresholds which ranged widely from 0.4 to
      3.0 ng/mL. Lower thresholds ranged from 0.4 to 1 ng/mL and classified the
      majority of cycles as abnormal as well as required very large number needed to
      treat (NNT) to increase one live birth. Frozen embryo transfer was cost-effective
      when P was >=1.5 ng/mL, with 12% of the population having an abnormal test result
      and an NNT of 13. Statistical and cost-effective thresholds clustered between 1.5
      and 2.0 ng/mL. CONCLUSION(S): Statistically significant thresholds for P were
      demonstrated as low as 0.4 ng/mL but resulted in a very large NNT to increase one
      live birth. A clinical benefit to a freeze-only approach was demonstrated above P
      thresholds ranging from 1.5 to 2.0 ng/dL. At these thresholds, elevated P has a
      demonstrable and clinically significant negative effect and captures a smaller
      percentage of the patient population at higher risk for fresh transfer failure,
      thus making freeze-only a cost-effective option.

PMID- 30196965
TI  - Impact of method of endometrial preparation for frozen blastocyst transfer on
      pregnancy outcome: a retrospective cohort study.
AB  - OBJECTIVE: To determine whether live birth rates differ by type of endometrial
      preparation in frozen embryo transfer (FET) cycles. DESIGN: Retrospective cohort
      study. SETTING: Academic fertility center. PATIENT(S): Reproductive-aged women
      undergoing autologous vitrified-warmed blastocyst FETs. INTERVENTION(S):
      Comparison of two methods of endometrial preparation: programmed FET (known as
      group A: luteal phase GnRH agonist suppression, oral E2, and IM P starting 5 days
      before ET) versus unstimulated FET (known as group B: hormone and ultrasound
      monitoring for follicle collapse to time transfer). MAIN OUTCOME MEASURE(S): Live
      birth rates in group A and group B. RESULT(S): Group A consisted of 923 cycles,
      and group B consisted of 105. When stratified by age at transfer, there was no
      difference in any of the measured outcomes, including live birth rates in
      adjusted models (adjusted odds ratio 1.0, 95% confidence interval 0.6-1.5),
      except in patients older than 40 years. These patients in group B had a 100%
      failure rate (n = 6). CONCLUSION(S): In most women, unstimulated endometrial
      preparation with luteal support before FET has similar success compared with
      exogenous hormone preparation. Women older than 40 years may benefit from
      programmed FETs owing to the challenges of increased cycle variability expected
      in that age group.

PMID- 30196966
TI  - Endometrial scratch injury for women with one or more previous failed embryo
      transfers: a systematic review and meta-analysis of randomized controlled trials.
AB  - OBJECTIVE: To investigate endometrial scratch injury (ESI) as an intervention to
      improve IVF outcome in women with a history of ET failure. DESIGN: Systematic
      review and meta-analysis. SETTING: Not applicable. PATIENT(S): Infertile women
      undergoing IVF after one or more failed ET. INTERVENTION(S): We included all
      randomized controlled trials of women undergoing IVF after one or more failed ET,
      where the intervention group received ESI and controls received placebo or no
      intervention. Pooled results were expressed as relative risk (RR) with a 95%
      confidence interval (95% CI). The review protocol was registered in PROSPERO
      before starting the data extraction (CRD42017082777). MAIN OUTCOME MEASURE(S):
      Live birth rate (LBR), clinical pregnancy rate (PR), multiple PR, miscarriage
      rate, ectopic pregnancy (EP) PR. RESULT(S): Ten studies were included (1,468
      participants). The intervention group showed higher LBR (RR 1.38, 95% CI 1.05
      1.80) and clinical PR (RR 1.34, 95% CI 1.07-1.67) in comparison to controls,
      without difference in terms of multiple PR, miscarriage rate, and EP PR. Double
      luteal ESI with pipelle was associated with the greatest effect on LBR (RR 1.54,
      95% CI 1.10-2.16) and clinical PR (RR 1.30, 95% CI 1.03-1.65). The ESI was
      beneficial for patients with two or more previous ET failure, but not for women
      with a single previous failed ET. No effect was found in women undergoing frozen
      thawed ET cycles. CONCLUSION(S): The ESI may improve IVF success in patients with
      two or more previous ET failures undergoing fresh ET. The ESI timing and
      technique seem to play a crucial role in determining its effect on embryo
      implantation.

PMID- 30196967
TI  - Cumulative live birth rate in freeze-all cycles is comparable to that of a
      conventional embryo transfer policy at the cleavage stage but superior at the
      blastocyst stage.
AB  - OBJECTIVE: To determine whether the freeze-all policy ensures a higher efficacy
      in terms of cumulative live birth rate (CLBR) in comparison with a conventional
      fresh/frozen embryo transfer (ET) approach in patients with normal ovarian
      response. DESIGN: Retrospective, matched, multicenter cohort study. SETTING:
      Private IVF centers. PATIENT(S): This study analyzed 564 completed IVF cycles in
      which an average of 12-18 oocytes were retrieved. In 435 cycles the conventional
      strategy was applied, with initial ET followed by frozen embryo replacements,
      whereas in 129 cycles the freeze-all policy was performed, with elective
      cryopreservation and deferred use of all viable embryos. INTERVENTION(S): None.
      MAIN OUTCOME MEASURE(S): The primary endpoint was CLBR. The secondary endpoint
      was cumulative clinical pregnancy rate. RESULT(S): Overall, statistically
      comparable CLBRs were achieved in the fresh/frozen and freeze-all groups (45.5%
      vs. 53.5%). Stratification of data for age and number of retrieved oocytes
      confirmed the absence of differences between the two groups. In a subanalysis in
      which the day of ET and cryopreservation were taken into account, a similar
      outcome was achieved in cleavage-stage groups (45.6% vs. 46.4%), whereas when ET
      was performed at the blastocyst stage the CLBR was significantly higher in the
      freeze-all group (45.3% vs. 66.7%). CONCLUSION(S): Our CLBR analysis indicates
      that clinical performance of the freeze-all policy is equivalent to that of the
      conventional strategy when ET is carried out at the cleavage stage. However, it
      seems to be superior if associated with cryopreservation and transfer at the
      blastocyst stage.

PMID- 30196968
TI  - Follicular fluid and supernatant from cultured cumulus-granulosa cells improve in
      vitro maturation in patients with polycystic ovarian syndrome.
AB  - OBJECTIVE: To study the effectiveness of a new in vitro maturation (IVM) approach
      based on heterologous follicular fluid (HFF) and supernatant of cumulus-granulosa
      cells (CGCs) mimicking the intact follicular microenvironment to rescue immature
      denuded oocytes (IDOs) of patients with polycystic ovary syndrome (PCOS) whose
      IVM or IVF outcomes remain poor. DESIGN: Randomized controlled trial. SETTING:
      University-affiliated private center. PATIENT(S): One hundred fifty-nine IDOs
      were obtained from 47 patients with PCOS. First, a simple IVM system (S-IVM; 40
      IDOs; control group) was compared with different protocols based on the addition
      of autologous follicular fluid (AFF-IVM; 44 IDOs), HFF (HFF-IVM; 42 IDO), or HFF
      with CGC isolated from seven women without PCOS and presenting 100% in vivo
      oocyte maturation (HFF/CGC-IVM; 33 IDOs). INTERVENTION(S): None. MAIN OUTCOME
      MEASURE(S): IVM outcomes were compared among the four groups (S-IVM, AFF-IVM, HFF
      IVM, HFF/CGC-IVM); then the vitro and in vivo maturation results (from controlled
      ovarian stimulation of PCOS patients) were compared for each group. RESULT(S):
      The HFF/CGC-IVM method gave the best yield of developed blastocysts per IDO
      compared with S-IVM, AFF-IVM, and HFF-IVM (27% vs. 2%, 2%, and 12%,
      respectively). The IVM rate with the HFF/CGC-IVM method was even higher than that
      compared with the in vivo maturation rate (79% vs. 42%), with significant
      improvement in the cleavage rate (71% vs. 61%). CONCLUSION(S): This adapted IVM
      system could be used to reach an acceptable result in meiotic competence and
      competent metaphase II oocytes capable of developing into intact embryos after
      fertilization and before transfer.

PMID- 30196969
TI  - Risks associated with fertility preservation for women with sickle cell anemia.
AB  - OBJECTIVE: To highlight the risk of complications among women with sickle cell
      anemia (SCA) receiving fertility preservation treatment (FPT) before
      hematopoietic stem cell transplant (HSCT). DESIGN: Single-center case series.
      SETTING: Academic fertility center. PATIENT(S): Women aged 15-32 years with SCA
      undergoing FPT before HSCT. INTERVENTION(S): Retrospective, systematic review.
      MAIN OUTCOME MEASURE(S): FPT modality, SCA complications during FPT. RESULT(S):
      Over an 8-year period (2009-2017), seven women with SCA ages 15-32 years (mean
      28.5 years) underwent FPT with embryo cryopreservation (n = 1), oocyte
      cryopreservation (n = 4), and ovarian tissue cryopreservation (n = 2). The five
      women subjects who underwent oocyte or embryo cryopreservation were treated with
      an antagonist controlled ovarian hyperstimulation protocol and individualized
      gonadotropin dosing. The trigger medications included leuprolide acetate (n = 2),
      and human chorionic gonadotropin (n = 3). Most patients (n = 5) received a
      disease-modifying therapy for SCA (hydroxyurea or chronic transfusions) before
      FPT. Three patients experienced periprocedural SCA complications that included
      life-threatening respiratory failure, painful crisis requiring interruption of a
      stimulation cycle, and severe postharvest painful crisis. CONCLUSION(S): Women
      with SCA may choose to undergo diverse FPT strategies before HSCT and are at risk
      for serious SCA-related complications. Evidence-based strategies to mitigate SCA
      related morbidity and to optimize fertility preservation outcomes are needed.

PMID- 30196970
TI  - When standard genetic testing does not solve the mystery: a rare case of
      preimplantation genetic diagnosis for campomelic dysplasia in the setting of
      parental mosaicism.
AB  - OBJECTIVE: To report a rare case of somatic mosaicism with a germline component
      of campomelic dysplasia in a woman undergoing in vitro fertilization with
      preimplantation genetic diagnosis (IVF-PGD). DESIGN: Case report. SETTING:
      Clinic. PATIENT(S): A 28-year old G2P0110 and her 34-year old husband had two
      previous pregnancies complicated by fetal campomelic dysplasia with suspected
      germline mosaic mutation. The couple, both phenotypically normal, underwent IVF
      PGD to reduce their chances of transmission. None of the embryos could initially
      be determined to be disease free, because all embryos shared either a maternal or
      a paternal short tandem repeat haplotype with the products of conception from her
      last pregnancy. INTERVENTION(S): Peripheral-blood cytogenomic single-nucleotide
      polymorphism (SNP) microarray to identify the carrier of the mutation, and IVF
      PGD to identify the disease-free embryo. MAIN OUTCOME MEASURE(S): Disease-free
      embryo. RESULT(S): Only one of the five euploid embryos was identified as disease
      free. CONCLUSION(S): A woman with suspected germline mosaicism for campomelic
      dysplasia was found to be a somatic mosaic with a germline component via a
      peripheral blood SNP microarray test. This identified her solitary disease-free
      embryo, which was transferred to her uterus but did not result in a viable
      pregnancy.

PMID- 30196972
TI  - Treatment of vaginal agenesis in Mayer-Rokitansky-Kuster-Hauser syndrome in
      Denmark: a nationwide comparative study of anatomical outcome and complications.
AB  - OBJECTIVE: To compare the long-term anatomical outcome and complications in
      treatments of vaginal agenesis in Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome.
      DESIGN: A historical comparative follow-up study using medical chart reviews.
      SETTING: Public hospitals. PATIENT(S): A nationwide cohort of patients diagnosed
      with MRKH syndrome (n = 168). INTERVENTION(S): McIndoe vaginoplasty (n = 54),
      self-dilation (n = 60), coital dilation (n = 20), Baldwin vaginoplasty (n = 4),
      Williams vaginoplasty (n = 3), Davydov vaginoplasty (n = 2), or no treatment (n =
      29). MAIN OUTCOME MEASURES(S): Mean vaginal depth at follow-up, anatomical
      treatment success rates at levels of >=6 cm, >=7 cm, and >=8 cm, complications,
      and resurgery. RESULT(S): Mean vaginal depths were 7.4 cm (95% confidence
      interval [CI] 6.8-8.1 cm), 7.3 cm (95% CI 6.7-7.9 cm), and 8.7 cm (95% CI 7.9-9.5
      cm) at follow-up in patients treated by McIndoe vaginoplasty, self-dilation, and
      coital dilation, respectively. Overall complication rates in the three groups
      were 35/54 (65%), 21/52 (35%), and 1/20 (5%), respectively. Eighteen (33%) of the
      patients who underwent McIndoe vaginoplasty needed resurgery. CONCLUSION(S): Our
      findings support the current recommendations of dilation therapy as the first
      line treatment of vaginal agenesis and emphasize the relevance of coital dilation
      in patients able to regularly engage in coital activity. However, further studies
      of functional outcome and patient satisfaction are needed.

PMID- 30196971
TI  - Transethnic and race-stratified genome-wide association study of fibroid
      characteristics in African American and European American women.
AB  - OBJECTIVE: To identify, through genome-wide association studies, genetic loci
      that associate with differences in fibroid size and number in a population of
      African American and European American women. DESIGN: Cross-sectional study.
      SETTING: Not applicable. PATIENT(S): Using BioVU, a clinical population from the
      Vanderbilt University Medical Center, and the Coronary Artery Risk Development in
      Young Adults cohort, a prospective cohort, we identified 1520 women (609 African
      American and 911 European American) with documented fibroid characteristics.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Outcome measurements include
      volume of largest fibroid, largest fibroid dimension, and number of fibroids
      (single vs. multiple). RESULT(S): In race-stratified analyses we achieved genome
      wide significance at a variant located between MAT2B and TENM2 (rs57542984, beta
      = 0.13; 95% confidence interval 0.09, 0.17) for analyses of largest fibroid
      dimension in African Americans. The strongest signal for transethnic analyses was
      at a variant on 1q31.1 located between PLA2G4A and BRINP3 (rs6605005, beta =
      0.24; 95% confidence interval 0.15, 0.33) for fibroid volume. Results from
      MetaXcan identified an association between predicted expression of the gene ER
      degradation enhancing alpha-mannosidase like protein 2 (EDEM2) in the thyroid and
      number of fibroids (Z score = -4.51). CONCLUSION(S): This study identified many
      novel associations between genetic loci and fibroid size and number in both race
      stratified and transethnic analyses. Future studies are necessary to further
      validate our study findings and to better understand the mechanisms underlying
      these associations.

PMID- 30196973
TI  - Oil-based or water-based contrast for hysterosalpingography in infertile women: a
      cost-effective analysis of a randomized controlled trial.
AB  - OBJECTIVE: To determine the cost effectiveness of the use of oil-based versus
      water-based contrast in infertile women undergoing hysterosalpingography (HSG).
      DESIGN: Economic evaluation alongside a multicenter randomized trial. SETTING:
      Hospitals. PATIENT(S): Infertile women with an ovulatory cycle, 18-39 years of
      age, low risk of tubal pathology. INTERVENTION(S): Use of oil-based versus water
      based contrast during HSG. MAIN OUTCOME MEASURE(S): Costs per additional ongoing
      pregnancy and per live birth within 6 months of randomization, incremental cost
      effective ratios (ICERs). RESULT(S): A total of 1,119 women were randomized to
      HSG (oil-based contrast, n = 557; water-based contrast, n = 562). After HSG, most
      women had no additional treatment; a minority had IUI or IVF. In the oil group,
      39.7% women had an ongoing pregnancy within 6 months of randomization versus
      29.1% women in the water group. There was a 10.7% increase in the live birth rate
      in the oil group. For ongoing pregnancy, the mean costs per couple were US$2,014
      in the oil group and US$1,144 in the water group, with a corresponding ICER of
      US$8,198 per additional ongoing pregnancy. For live birth, the mean costs per
      couple were US$11,532 in the oil group and US$8,310 in the water group, with a
      corresponding ICER of US$30,112 per additional live birth. CONCLUSION(S):
      Hysterosalpingography with oil-based contrast results in higher 6-month ongoing
      pregnancy and live birth rate. If society is willing to pay US$8,198 for an
      additional ongoing pregnancy, HSG with oil-based contrast is a cost-effective
      strategy compared with HSG with water-based contrast for infertile, ovulatory
      women at low risk for tubal pathology. CLINICAL TRIAL REGISTRATION NUMBER: Dutch
      Trial Register, NTR 6577 (www.trialregister.nl).

PMID- 30196974
TI  - Vitamin D levels are not associated with ovarian reserve in a group of infertile
      women with a high prevalance of diminished ovarian reserve.
AB  - OBJECTIVE: To determine whether a relationship exists between vitamin D (25OH-D)
      levels and ovarian reserve parameters (antimullerian hormone [AMH] and FSH
      levels) in a large cohort of infertile women with a high prevalence of diminished
      ovarian reserve. DESIGN: Retrospective cohort study. SETTING: Academically
      affiliated private fertility center. PATIENT(S): A total of 457 infertile women
      21-50 years of age who had baseline hormone measurements. INTERVENTION(S): None.
      MAIN OUTCOME MEASURE(S): Statistical analyses to determine whether a relationship
      exists between AMH, FSH, and serum 25OH-D levels. RESULT(S): As defined by 25OH-D
      <20.0 ng/mL, 74/457 patients (16.2%) had vitamin D deficiency. AMH and FSH levels
      did not vary between women with vitamin D deficiency and those with normal levels
      (0.8 +/- 3.0 vs. 0.5 +/- 1.6 ng/mL [P=.18] and 9.4 +/- 7.2 vs. 9.2 +/- 9.5 mIU/mL
      [P=.54], respectively). Multivariate linear regression analysis of log
      transformed AMH and FSH with 25OH-D levels adjusted for age, body mass index, and
      seasonal variation confirmed lack of association. Receiver operating
      characteristic (ROC) analysis to determine if 25OH-D levels are predictive of AMH
      showed areas under the ROC curves (AUCs) for women <38 years of age to be 0.501,
      0.554, and 0.511 for AMH threshold values of 0.5 ng/mL, 1.0 ng/mL, and 5.0 ng/mL,
      respectively. For women >=38 years respective AUC values were 0.549, 0.545, and
      0.557 ng/mL. CONCLUSION(S): Vitamin D levels were not associated with ovarian
      reserve in a large group of infertile women with a high prevalence of diminished
      ovarian reserve. Previously reported vitamin D-associated outcomes in infertility
      patients may, therefore, be mediated by factors other than ovarian reserve.

PMID- 30196975
TI  - Elevated peritoneal fluid ceramides in human endometriosis-associated infertility
      and their effects on mouse oocyte maturation.
AB  - OBJECTIVE: To characterize the peritoneal fluid (PF) sphingolipid profile in
      endometriosis-associated infertility (EAI), and to assess the plausible
      functional role(s) of ceramides in oocyte maturation potential. DESIGN:
      Retrospective case-control study and in vitro mouse oocyte study. SETTING:
      University-affiliated hospital and university laboratory. SUBJECTS: Twenty-seven
      infertile patients diagnosed with endometriosis and 20 infertile patients who did
      not have endometriosis; BALB/c female mice. INTERVENTION(S): None. MAIN OUTCOME
      MEASURE(S): PF sphingolipid concentrations. Number of metaphase II (MII) mouse
      oocytes. RESULT(S): Liquid chromatography-tandem mass spectrometry revealed 11
      significantly elevated PF sphingolipids in infertile women with severe
      endometriosis compared with infertile women without endometriosis (change >50%,
      false discovery rate <=10%). Logistic regression analysis identified three very
      long-chain ceramides potentially associated with EAI. Functional studies revealed
      that very-long-chain ceramides may compromise or induce murine MII oocyte
      maturation. The oocyte maturation effects induced by the very long-chain
      ceramides were triggered by alterations in mitochondrial superoxide production in
      a concentration-dependent manner. Scavenging of mitochondrial superoxide reversed
      the maturation effects of C24:0 ceramide. CONCLUSION(S): EAI is associated with
      accumulation of PF very-long-chain ceramides. Mouse studies demonstrated how
      ceramides affect MII oocyte maturation, mediating through mitochondrial
      superoxide. These results provide an opportunity for direct functional readout of
      pathophysiology in EAI, and future therapies targeted at this sphingolipid
      metabolism may be harnessed for improved oocyte maturation.

PMID- 30196976
TI  - Pre-, intra-, and postoperative management of Robert's uterus.
AB  - OBJECTIVES: To demonstrate a minimally invasive approach and management in three
      different types of Robert's uterus. DESIGN: Video presentation of surgical and
      ultrasound techniques. SETTING: University hospital and two private centers.
      PATIENTS: Patients with three types of Robert's uterus; a rare form of septate
      uterus consisting of non-communicating hemicavity, a contralateral unicornuate
      uterine cavity in a single uterine body with normal fundus: with large
      hematometra in the blind hemi-cavity and acute pelvic pain; with an inactive
      blind hemi-cavity without hematometra and recurrent miscarriages; and with small
      hematometra in the blind hemi-cavity. INTERVENTIONS: Three-dimensional ultrasound
      with saline infusion sonohysterography and automatic volume calculation software
      (SonoHySteroAVC) were used for differential diagnosis and surgical planning.
      Transrectally guided hysteroscopic metroplasty, a incision of myometrium between
      two parts of cavities by resectoscope and Collin's electrode, were performed and
      recorded. Sequentional balloon anti-adhesion therapy and three-dimensional
      ultrasound with saline infusion sonohysterography with SonoHysteroAVC were used
      in post-operative management. MAIN OUTCOME MEASURES: Pre-, intra- and
      postoperative findings regarding uterine morphology, feasibility of surgery and
      anatomical and clinical outcomes. RESULTS: A successful unification of non
      communicating and communicating uterine cavity parts during surgery, better shape
      and several times higher volume of uterine cavity, and total elimination of pain
      associated with obstruction after healing period were recorded. CONCLUSIONS:
      Three-dimensional ultrasound techniques seem to be the best tool for complex pre-
      and postoperative management of Robert's uterus. Minimally invasive ultrasound
      guided hysteroscopic metroplasty should be considered as the first choice of
      treatment because of the potential for normalization of uterine morphology and
      function.

PMID- 30196977
TI  - The role of rumination in the guilt associated with bereavement according to
      cause of death.
AB  - The purpose of this study was to analyse the role rumination plays in the
      relationship between cause of death and the guilt present during bereavement. The
      sample consisted of 90 people that had suffered a loss due to an expected or
      unexpected natural death, suicide or accident. The results suggest that
      rumination increases the levels of guilt felt by people that had suffered a loss
      due to suicide compared to those whose loss was due to an expected natural death.
      These findings contribute to a better understanding of the mechanisms with an
      influence on bereavement.

PMID- 30196978
TI  - Synthesis and biological evaluation of novel heteroring-annulated pyrrolino
      tetrahydroberberine analogues as antioxidant agents.
AB  - Tetrahydroberberine (THB), otherwise known as canadine, is a natural alkaloid
      showing significant pharmacological properties and antioxidant protection against
      oxidative damage. Herein, we synthetized structurally complex THB analogues,
      namely pyrrolino-tetrahydroberberines (PTHBs) 4a-g, containing the pyrrolino[2,3
      b]pyridine system, by means of the reactions of 1,2-diaza-1,3-dienes and 7,8
      dihydroberberine. Aim of the study was to explore the in vitro antioxidant
      properties of PTHBs in comparison to THB thus to identify the most effective
      against free radical-induced oxidative injury, by using three different
      antioxidant tests: the ORAC method, the DNA nicking assay, and the DCFH-DA
      cellular assay. As a result, PTHB 4d emerged among the other THB analogues by
      exhibiting the best antioxidant properties. First, it was the only compound
      having an ORAC value completely comparable to that of THB, indicating the same
      ability to neutralize peroxyl radicals. Secondly, 4d showed an even better
      antioxidant capacity than THB in protecting DNA against ferrous ion-induced
      strand breaks. These observations were also confirmed in NCTC-2544 human
      keratinocytes exposed to hydrogen peroxide. Indeed, 4d protected cells against
      oxidation more efficiently than THB both in the short (1 and 3 h) and long (24 h)
      period of incubation, possibly suggesting increased cell membrane permeability
      and/or intracellular stability of 4d as compared to THB.

PMID- 30196980
TI  - Response from Authors.

PMID- 30196979
TI  - Carbon monoxide poisoning in a young, healthy patient: A case study of heart
      failure recovery after Hyperbaric Oxygenation Treatment.

PMID- 30196981
TI  - Stimulus-specific adaptation in the anesthetized mouse revealed by brainstem
      auditory evoked potentials.
AB  - Neural responses to sensory inputs in a complex and natural environment must be
      weighted according to their relevance. To do so, the brain needs to be able to
      deal with sudden stimulus fluctuations in an ever-changing acoustic environment.
      Stimulus-specific adaptation (SSA) is a phenomenon of some neurons along the
      auditory pathway that show a reduced response to repetitive sounds while
      responsive to those that occur rarely. SSA has been shown from the inferior
      colliculus to auditory cortex, but has not been detected in the cochlear nucleus.
      To discover where SSA is first generated along the auditory pathway, auditory
      brainstem responses (ABRs) to pure tones were evaluated in anesthetized mice
      using an oddball paradigm. Using a typical narrow band-pass filter, changes in
      the ABRs suggest unspecific short-term adaptation may occur as early as the
      auditory nerve fibers. Furthermore, after applying a wide band-pass filter 
      allowing the visualization of a late slow wave in the ABR- we found a reduction
      of the amplitude of the response to repetitive sounds, compared to rare ones, in
      the slow wave component P0 that follow the fast wave V. Previous studies have
      shown the P0 shows temporal correlation with the sustained responses of inferior
      colliculus, thus we suggest that this nucleus is the first to show stimulus
      specific adaptation in the auditory pathway.

PMID- 30196983
TI  - One-stage revision anterior cruciate ligament reconstruction in cases with
      excessive tunnel osteolysis. Results of a new technique using impaction bone
      grafting.
AB  - BACKGROUND: This level IV study describes a new one-stage procedure for revision
      ACL reconstruction in cases with extreme tunnel widening. METHODS: Eight
      consecutively treated subjects requiring ACL revision and presenting with
      excessive tunnel widening (87.5% to 250% tunnel enlargement) were included in
      this study. The graft-tunnel mismatch was resolved in this one-stage revision
      procedure by the use of custom-made eight to 10 mm cylindrical shaped bone
      allografts in a press-fit construct with the ACL-graft in combination with the
      usual fixation devices for ACL-reconstruction. All subjects were evaluated pre
      operatively and at a minimum follow-up of one year by the IKDC objective and
      subjective scores, KOOS, and Tegner activity scale. RESULTS: Mean improvement was
      24.8 +/- 16.1 on the KOOS evaluation (P-value 0,006) and 38.1 +/- 16.8 on the
      IKDC subjective score (P-value 0,001). The objective IKDC scores improved
      significantly with an average of one grade (P-value 0,038). Anterior laxity as
      determined on the KT-1000 arthrometer improved with an average of 3.63 mm
      compared to the situation before primary reconstruction, and the Pivot-shift test
      was negative in all but one patient after the revision procedure while positive
      in all patients before primary reconstruction. CONCLUSION: This new surgical
      technique using eight to 10 mm allograft bone cylinders for the management of
      excessive tunnel enlargement at single stage revision ACL reconstruction delivers
      excellent results after minimum one year of follow-up. The results of this study
      have the potential to lower the threshold for one-stage surgery in ACL revision
      complicated by extreme tunnel widening.

PMID- 30196982
TI  - A TCP-based early regression index predicts the pathological response in neo
      adjuvant radio-chemotherapy of rectal cancer.
AB  - PURPOSE: Introducing a radiobiological index based on early tumor regression
      during neo-adjuvant radio-chemotherapy (RCT, including oxaliplatin) of rectal
      adenocarcinoma and testing its discriminative power in predicting the tumor
      response. METHODS: Seventy-four patients were treated with Helical Tomotherapy
      following an adaptive (ART) protocol (41.4 Gy/18 fr, 2.3 Gy/fr) delivering a
      simultaneous integrated boost on the residual tumor in the last 6 fractions up to
      45.6 Gy. T2-weighted MRI were taken before (MRIpre) and at mid (MRImid) therapy
      and the corresponding tumor volumes were considered (Vpre,Vmid). The "Early
      Regression Index" [Formula: see text] was introduced and its discriminative power
      was assessed in terms of AUC, sensitivity/specificity, positive/negative
      predictive value (PPV/NPV). Two end-points were considered: (a) pathological
      complete response (pCR) or clinical complete response followed by watch-and-wait,
      (cCR); (b) limited response (residual vital cells (RVC) in the surgical specimen
      >10%). RESULTS: Complete data were available for 65 patients: pCR, cCR and RVC
      >10% were 20, 2 and 19 respectively. The discriminative power of ERITCP was
      moderately high (AUC = 0.81/0.75 for /pCRorcCR/RVC >10% respectively, p <
      0.0005). ERITCP was highly sensitive (86-89%) with very high NPV (90-94%). The
      discriminative power of ERITCP was confirmed on a subgroup of 44/65 patients when
      considering tumor volumes delineated by a skilled radiologist. CONCLUSION: A
      radiobiologically consistent index based on early regression showed high
      performances in predicting the pathological response after neo-adjuvant RCT for
      rectal cancer with relevant potentialities for ART/treatment customization.

PMID- 30196984
TI  - Ultrasound-assisted heterogeneous activation of persulfate by nano zero-valent
      iron (nZVI) for the propranolol degradation in water.
AB  - This study investigated the degradation of propranolol (PRO), a beta (beta)
      blockers, by nano zero-valent iron (nZVI) activated persulfate (PS) under
      ultrasonic irradiation. Effects of several critical factors were evaluated,
      inclusive of PS concentration, nZVI dosage, ultrasound power, initial pH, common
      anions, and chelating agent on PRO degradation kinetics. Higher PS concentration,
      nZVI dosage and ultrasound power as well as acidic pH favored the PRO
      degradation. Conversely, anions and chelating agent took on the inhibitory effect
      towards PRO degradation to different extents. Furthermore, the variations of
      morphology and surface composition of nZVI before and after the reaction were
      characterized by TEM, XRD and XPS. Finally, on the basis of identified
      degradation intermediates by LC/MS/MS analysis, this work tentatively proposed
      the degradation pathways. These encouraging results suggest that US/nZVI/PS
      process is a promising strategy for the treatment of PRO-induced water pollutant.

PMID- 30196985
TI  - Association of increased microvessel density with skeletal extramedullary disease
      relapse in multiple myeloma patients who have skeletal extramedullary disease at
      diagnosis.
AB  - The aim of the study was to investigate whether microvessel density (MVD) could
      be associated with skeletal extramedullary disease relapse (skeletal-EMDR) in
      patients with multiple myeloma (MM) who have skeletal-EMD at diagnosis. Seventy
      nine newly diagnosed MM patients who have skeletal-EMD were retrospectively
      enrolled in this study. The 4-year cumulative incidence of skeletal-EMDR was
      35.0%+/-8.3%. The 4-year probability of overall survival (OS) was 54.0%+/-7.6%.
      Multivariate analysis showed that skeletal-EMDR (HR = 4.144; 95% CI: 1.608
      10.685; P = 0.003) was independently associated with inferior OS for the MM
      patients who have skeletal-EMD at diagnosis. The factors associated with skeletal
      EMDR were MVD (HR = 3.990, 95%CI:1.136-14.018; P = 0.031), white blood cell (WBC)
      (HR = 0.262, 95% CI:0.090-0.769; P = 0.015), and the EMD sites involved at onset
      (HR = 0.263, 95% CI: 0.074-0.937; P = 0.039). The MVD in patients with thoracic
      and lumbar vertebrae as the involved sites at diagnosis was significantly lower
      than those with other sites involved (41.59 +/- 14.39 vs. 60.82 +/- 35.14,
      P=0.001). Our data suggest that increased MVD could be used to predict skeletal
      EMDR, which is associated with inferior survival in patients with MM who have
      skeletal-EMD at diagnosis.

PMID- 30196986
TI  - Upregulation of Periostin expression in the pathogenesis of ameloblastoma.
AB  - Ameloblastoma(AB) is an aggressive and slow-growing tumor with high recurrence
      rate, which arises from odontogenic epithelium. AB mostly shows osteolytic
      growth, but the specific pathogenesis is not yet clear. Periostin is a considered
      a prominent oncogene, which was mainly produced by osteoblasts and their
      precursors cells, it have been proved that Periostin play an important role in
      bone lysis. However, the precise role of Periostin in AB progression remains
      unknown. In this article, the surgical specimens from cases of AB were collected,
      and the Periostin expression was tested and the results were analyzed for
      possible correlations with clinical characteristics. In addition, the
      proliferation,cell cycle and migration of AM-1 cells were evaluated after
      transfection of siPeriostin. The results showed that Periostin levels were
      significantly higher in patients with AB than in controls. Moreover, Periostin
      levels in patients with AB were significantly associated with the number of
      disease. Furthermore, the results suggested that Periostin expression
      significantly promoted the proliferation and migration, in addition to cell cycle
      progression of AM-1 cells. The present study demonstrated that Periostin may be
      important in the pathogenesis and progression of AB and indicated its potential
      therapeutic value.

PMID- 30196988
TI  - Functions of transcription factors NF-kappaB and Nrf2 in the inhibition of LPS
      stimulated cytokine release by the resin monomer HEMA.
AB  - OBJECTIVE: Resin monomers like 2-hydroxyethyl methacrylate (HEMA) interfere with
      effects induced by stressors such as lipopolysaccharide (LPS) released from
      cariogenic microorganisms. In this study, mechanisms underlying monomer-induced
      inhibition of the LPS-stimulated secretion of inflammatory cytokines from
      immunocompetent cells were investigated. METHODS: Secretion of pro-inflammatory
      cytokines TNF-alpha, IL-6 and the anti-inflammatory IL-10 from RAW264.7 mouse
      macrophages exposed to LPS and HEMA (0-6-8mM) was determined by ELISA. The
      formation of reactive oxygen (ROS) and nitrogen species (RNS) was determined by
      flow cytometry (FACS) after staining of cells with specific fluorescent dyes.
      Cell viability was analyzed by FACS, and protein expression was detected by
      Western blotting. RESULTS: Secretion of TNF-alpha, IL-6 and IL-10 from LPS
      stimulated cells increased after a 24h exposure. A HEMA-induced decrease in
      cytokine secretion resulted from the inhibition of LPS-stimulated NF-kappaB
      activation. Nuclear translocation of NF-kappaB was inhibited possibly as a result
      of enhanced levels of hydrogen peroxide (H2O2) and nitric oxide (NO) in HEMA
      exposed cells. Oxidative stress caused by HEMA-induced formation of H2O2 and LPS
      stimulated peroxynitrite (ONOO) also enhanced nuclear expression of Nrf2 as the
      major regulator of redox homeostasis, as well as Nrf2-controlled stress protein
      HO-1 to inhibit NF-kappaB activity. HEMA inhibited the LPS-stimulated expression
      of NOS (nitric oxide synthase) to produce NO but counteracted the expression of
      Nox2, which forms superoxide anions that combine with NO to peroxynitrite.
      CONCLUSIONS: Resin monomers like HEMA inhibit LPS-stimulated NF-kappaB activation
      essential for cytokine release as a crucial response of immunocompetent cells of
      the dental pulp to invading cariogenic pathogens.

PMID- 30196989
TI  - Uptake of the English Bowel (Colorectal) Cancer Screening Programme: an update 5
      years after the full roll-out.
AB  - BACKGROUND: The initial roll-out of the English Bowel (Colorectal) Cancer
      Screening programme, during 2006 and 2009, found uptake to be low (54%) and
      socially graded. The current analysis used data from 2010 to 2015 to test whether
      uptake is increasing and becoming less socially graded over time. METHODS:
      Postcode-derived area-level uptake of 4.4 million first-time invitees, stratified
      by gender and the year of the first invitation (2010-2015), was generated using
      the National Bowel Cancer Screening System. Data were limited to people aged 60
      64 years. Binomial regression tested for variations in uptake by the year of
      invitation, gender, region, area-based socio-economic deprivation and area-based
      ethnic diversity. RESULTS: Overall, the first-time colorectal cancer (CRC)
      screening uptake across 6 years was 52% (n = 2,285,996/4,423,734) with a decline
      between 2010 and 2015 (53%, 54%, 52%, 50%, 49%, 49% respectively). Uptake
      continued to be socially graded between the most and the least deprived area
      level socio-economic deprivation quintiles (43% vs 57%), the most and the least
      area-based ethnic diversity quintiles (41% vs 56%) and men and women (47% vs
      56%). Multivariate analysis demonstrated the effects of year, deprivation,
      ethnicity and gender on uptake. The effect of deprivation was more pronounced in
      the most deprived area quintile between men and women (40% vs 47%) than the least
      deprived area quintile (52% vs 62% respectively). CONCLUSION: We did not find
      evidence of change in uptake patterns in CRC screening since its initial launch
      10 years ago. The programme is unlikely to realise its full public health
      benefits and is en route to widening inequalities in CRC outcomes.

PMID- 30196987
TI  - Expression of RNA-binding protein LIN28 in classic gastric hepatoid carcinomas,
      gastric fetal type gastrointestinal adenocarcinomas, and hepatocellular
      carcinomas: An immunohistochemical study with comparison to SALL4, alpha
      fetoprotein, glypican-3, and Hep Par1.
AB  - INTRODUCTION: Gastric hepatoid carcinomas (GHCs) include type I (classic) and
      type II (fetal type gastrointestinal adenocarcinoma). The classic type shows
      overlapping morphologic features with those of hepatocellular carcinoma (HCC).
      The aim of this study is to investigate expression of LIN28 in GHCs and explore
      its utility to distinguish classic GHC from HCC. METHODS: We investigated
      immunohistochemical expression of LIN28 in 93 primary GHCs (47 type I, 46 type
      II) and 60 HCCs with comparison to SALL4, AFP, glypican-3, Hep Par1, p-CEA and
      CK7. We also stained LIN28 and SALL4 in 52 conventional gastric adenocarcinomas
      to assess their specificity in gastric carcinomas. RESULTS: Classic GHCs and
      fetal type gastrointestinal adenocarcinomas showed positive LIN28 in 21/47 (45%)
      and 10/46 (22%), SALL4 in 41/47 (87%) and 36/46 (78%), AFP in 30/46 (65%) and
      33/46 (72%), glypican-3 in 31/41 (76%) and 24/38 (63%), Hep Par1 in 27/41 (66%)
      and 28/37 (76%), and CK7 in 15/40 (38%) and 25/38 (66%), respectively. p-CEA
      staining was seen in 19/44 (43%) classic GHCs. Among HCCs, LIN28, SALL4, AFP,
      glypican-3, Hep Par1, p-CEA and CK7 was seen in 1/60 (2%), 0/60 (0%), 6/30 (20%),
      23/30 (77%), 29/30 (97%), 28/30 (93%) and 21/30 (70%) cases, respectively. LIN28
      and SALL4 staining was seen in 2/52 (4%) and 14/52 (27%) gastric conventional
      adenocarcinomas, respectively. The sensitivity and specificity of distinguishing
      classic GHCs from HCCs was 45% and 98% for LIN28, 87% and 100% for SALL4, 65% and
      80% for AFP, 76% and 30% for glypican-3, 66% and 3% for Hep Par1, 43% and 7% for
      p-CEA, and 38% and 30% for CK7, respectively. Combining LIN28 and SALL4 increased
      the sensitivity to 96% with 98% specificity to distinguish classic GHCs from
      HCCs. CONCLUSIONS: LIN28 is a very specific marker (98% specificity) for
      distinguishing classic GHCs from HCCs though it is not as sensitive as SALL4.
      AFP, glypican-3, Hep Par1 and p-CEA are not useful in distinguishing classic GHCs
      from HCCs. Combining LIN28 and SALL4 increased the sensitivity to distinguish
      classic PHCs from HCCs.

PMID- 30196990
TI  - The nephrotoxicity of immune checkpoint inhibitor-based combinations.

PMID- 30196991
TI  - An inherited KMT2B duplication variant in a Chinese family with dystonia and/or
      development delay.

PMID- 30196992
TI  - The lead contaminated land treated by the circulation-enhanced electrokinetics
      and phytoremediation in field scale.
AB  - Some agricultural lands have been contaminated by heavy metals in Taiwan for
      several decades, because the irrigation system was polluted by wastewater. In
      this study, a circulation-enhanced electrokinetics (CEEK) and phytoremediation
      were applied alternately to the real lead-contaminated site. In the beginning,
      the CEEK was used; then, the corn plants were raised. After this
      phytoremediation, the CEEK was employed again. Experimental results show that the
      lead concentration can be reduced from 5672 mg/kg to 2083 mg/kg (around 63%)
      after the three-stage treatment (CEEK + corn + CEEK). At each stage, CEEK, corn
      plants, and CEEK can remove around 25%, 5%, and 30% lead from the soil,
      respectively. During the whole process, the soil pH can maintain around neutral
      range and the electrical conductivity of soil was stable. The electricity
      consumption of the CEEK was quite low (89 USD per ton) and the corn plants still
      were alive throughout the remediation.

PMID- 30196993
TI  - Gestational diabetes and postnatal depressive symptoms: A prospective cohort
      study in Western China.
AB  - BACKGROUND: Gestational diabetes mellitus (GDM) can lead to adverse birth
      outcomes, but its effect on postnatal depression has not been thoroughly
      investigated, especially in Asian populations. AIM: To determine the prospective
      association between GDM and postnatal depressive symptoms in Western China.
      METHODS: A prospective cohort study of 1449 mothers was conducted in Chengdu,
      capital city of Sichuan Province. GDM was diagnosed during pregnancy using oral
      glucose tolerance tests. Maternal depressive symptoms were measured at 32-37weeks
      of gestation, then at one and three months after giving birth using a validated
      Chinese version of the Edinburgh Postnatal Depression Scale (EPDS). Associations
      between the postnatal EPDS scores, GDM status and blood glucose levels were
      assessed by multivariable mixed-effects regression models, accounting for
      baseline EPDS scores of the cohort and other confounding factors. FINDINGS:
      Compared to the non-GDM group (n=1220), women with GDM (n=229, 15.8%) reported
      significantly higher mean EPDS scores at both 1-month (p=0.02) and 3-month
      (p<0.01) postpartum. Similarly, high levels of fasting, 1-h and 2-h blood glucose
      levels during pregnancy were associated with increased EPDS scores. Mixed-effects
      models further confirmed the positive association between GDM status and
      postnatal depressive symptoms, even though the mean EPDS scores decreased
      substantially over the three time points. CONCLUSION: Chinese women with GDM were
      more susceptible to postnatal depression than others without the condition,
      despite their depressive symptoms reducing over time after childbirth. It is thus
      important to raise awareness of postnatal depression amongst healthcare
      professionals who care for women with GDM.

PMID- 30196994
TI  - Integrated chemiluminescence-based lab-on-chip for detection of life markers in
      extraterrestrial environments.
AB  - The detection of life markers is a high priority task in the exploration of the
      Solar System. Biochips performing in-situ multiplex immunoassays are a very
      promising approach alternative to gas chromatography coupled with mass
      spectrometry. As part of the PLEIADES project, we present the development of a
      chemiluminescence-based, highly integrated analytical platform for the detection
      of biomarkers outside of the Earth. The PLEIADES device goes beyond the current
      lab-on-chip approaches that still require bulky external instrumentation for
      their operation. It exploits an autonomous capillary force-driven microfluidic
      network, an array of thin-film hydrogenated amorphous silicon photosensors, and
      chemiluminescence bioassays to provide highly sensitive analyte detection in a
      very simple and compact configuration. Adenosine triphosphate was selected as the
      target life marker. Three bioassay formats have been developed, namely (a) a
      bioluminescence assay exploiting a luciferase mutant with enhanced thermal and pH
      stability and (b and c) binding assays exploiting antibodies or functional
      nucleic acids (aptamers) as biospecific recognition elements and peroxidase or
      DNAzymes as chemiluminescence reporters. Preliminary results, showing limits of
      detection in the nanomolar range, confirm the validity of the proposed approach.

PMID- 30196996
TI  - Epicardial adipose tissue: The new target for statin therapy.

PMID- 30196995
TI  - Incidence of contrast-induced acute kidney injury in a large cohort of all-comers
      undergoing percutaneous coronary intervention: Comparison of five contrast media.
AB  - BACKGROUND: There is controversy as to whether iso-osmolar contrast media (IOCM)
      are associated with lower risk of contrast-induced acute kidney injury (CI-AKI),
      compared with low-osmolar contrast media (LOCM). We aimed to evaluate if a
      differential risk of CI-AKI exists after percutaneous coronary intervention (PCI)
      according to different contrast media (CM) types. METHODS: We performed a single
      center retrospective study in a cohort of all-comers undergoing PCI between
      January 2012 and December 2016. CI-AKI was defined as an increase in serum
      creatinine >=0.3 mg/dl or >=50% within 72 h from PCI. IOCM were represented by
      iodixanol, whereas four different LOCM were utilized (ioversol, iopromide,
      iomeprol, iobitridol). Multiple-treatment inverse probability of treatment
      weighting (IPTW)-adjusted logistic regression analysis was performed to identify
      whether CM type was an independent predictor of CI-AKI. RESULTS: We included 2648
      subjects (ioversol, n = 272; iopromide, n = 818; iomeprol, n = 611; iobitridol, n
      = 460; iodixanol, n = 487). CI-AKI occurred in 300 patients (11.7%) overall, with
      no differences across CM groups (ioversol 13.0%, iopromide 11.5%, iomeprol 10.2%,
      iobitridol 13.9%, iodixanol 11.3%; p = 0.42). CI-AKI requiring dialysis was
      observed in 8 patients (0.3%) overall (p = 0.50). On IPTW-adjusted analysis, none
      of the LOCM was associated with a significantly different risk of CI-AKI compared
      with iodixanol: ioversol OR 0.986 (95% confidence interval [CI] 0.611-1.591),
      iopromide OR 0.870 (95% CI 0.606-1.250), iomeprol OR 0.904 (95% CI 0.619-1.319),
      iobitridol OR 1.258 (95% CI 0.850-1.861). CONCLUSIONS: In a large cohort of all
      comers undergoing PCI, there were no differences in the adjusted risk of CI-AKI
      across 4 LOCM, compared with iodixanol.

PMID- 30196997
TI  - MALAT1/miR-204/LC3-II: A potential regulated axis of autophagy in myocardial
      ischemia-reperfusion injury.

PMID- 30196999
TI  - Optimize the comprehensive evaluation of hemodynamical significance by coronary
      CT angiography.

PMID- 30196998
TI  - Ventricular tachycardia ablation in structural heart disease: Impact of ablation
      strategy and non-inducibility as an end-point on long term outcome.
AB  - BACKGROUND: To investigate the long term outcomes after catheter ablation (CA) of
      ventricular tachycardia (VT) in the context of structural heart disease in a
      multicenter cohort. The impact of different ablation strategies (substrate
      ablation versus activation guided versus combined) and non-inducibility as an end
      point was evaluated. METHODS: Data was pooled from prospective registries at 5
      centres over a 5 year period. Success was defined as survival free from recurrent
      ventricular arrhythmias (VA). Multivariate analysis of factors predicting
      survival free from VA was analysed by Cox regression. RESULTS: Five hundred sixty
      six patients underwent CA for VT. Patients were 64 +/- 15 years. Left ventricular
      ejection fraction was 35 +/- 15% and 66% had ischaemic heart disease. At 2.3 (IQR
      1.0-4.2) years, success was achieved in 44% after a single procedure, rising to
      60% after repeat procedures. Mortality at final follow up was 22%. Multivariate
      analysis showed that higher left ventricular ejection fraction, younger age,
      ischaemic heart disease, and non-inducibility of VA predicted long term survival
      free from VA (all p < 0.05). There was no impact of the approach to ablation.
      CONCLUSION: CA eliminates VT in a large proportion of patients long term.
      Ablation strategy did not impact outcome and hence substrate ablation is a
      reasonable initial strategy. Non-inducibility of VA predicted survival free from
      VA and may be worth pursuing as a procedural end-point.

PMID- 30197000
TI  - How clinicians can minimize transfusion-related adverse events?
AB  - OBJECTIVES: Transfusion-related adverse events (TRAE) can contribute to patient
      morbidity and mortality. In this brief narrative review, the strategies that
      clinicians can apply at the bedside to avoid TRAE are discussed. METHODS:
      Strategies to avoid the following five types of TRAE were reviewed: transfusion
      associated circulatory overload (TACO), transfusion-related acute lung injury
      (TRALI), transfusion-associated hypothermia (TAH), transfusion-related allergic
      reactions (TRAR) and acute haemolytic transfusion reactions (AHTR). RESULTS:
      Minimizing exposure to blood components is fundamental to TRAE avoidance. Pre
      transfusion assessment can identify patients at risk of TACO, TRAR and TAH, and
      avoidance steps implemented. Preventive strategies for TACO include lower
      transfusion rate, 'one unit at a time' transfusion policy and possibly diuretic
      medication. Patients with past history of TRAR should preferably be given plasma
      free blood components; anti-histamine medication prior to transfusion could be
      considered. TAH is common in the massive transfusion setting, particularly trauma
      patients. Warming of patients are key strategies to avoid TAH. Identification of
      patients at risk of TRALI is more opaque; however, any measures that limit
      pulmonary inflammation prior to transfusion may decrease the risk of TRALI.
      Causes of AHTR are commonly due to human error and failure to apply rigorous
      cross-checks of patient and issued RBC component blood groups. CONCLUSIONS:
      Beneficial strategies to avoid TRAE include judicious use of blood components,
      identification of high-risk patients, adherence to recommended clinical processes
      and awareness of TRAE pathophysiology. More evidence is warranted to better guide
      clinicians in the prevention of TRAE.

PMID- 30197001
TI  - LncRNA LINC00968 accelerates the proliferation and fibrosis of diabetic
      nephropathy by epigenetically repressing p21 via recruiting EZH2.
AB  - Emerging evidence have indicated the vital roles of long noncoding RNAs (lncRNAs)
      in the pathophysiological process of diabetic nephropathy. However, the deepgoing
      mechanism that lncRNAs regulate the diabetic nephropathy pathogenesis is still
      ambiguous. In present study, we found that lncRNA LINC00968 expression was high
      expressed in the diabetic db/db mouse tissue and high-glucose induced mesangial
      cells. Functional experiments indicated that LINC00968 silencing by siRNAs
      significantly inhibited the proliferation and cycle progression, and decreased
      the extracellular matrix (ECM) proteins (fibronectin, collagen IV) expression in
      the high glucose induced of mesangial cells. RNA immunoprecipitation (RIP) and
      chromatin immunoprecipitation (ChIP) assay revealed that LINC00968 recruit EZH2
      to the promoter of p21 to inhibit its expression. In summary, our results support
      the conclusion that lncRNA LINC00968 accelerates the proliferation and fibrosis
      of mesangial cells by epigenetically repressing p21 via recruiting EZH2,
      providing a novel insight for the diabetic nephropathy pathogenesis.

PMID- 30197002
TI  - Targeting CD26 suppresses proliferation of malignant mesothelioma cell via
      downmodulation of ubiquitin-specific protease 22.
AB  - Malignant pleural mesothelioma (MPM) is an aggressive malignancy arising from
      mesothelial lining of pleura. It is associated with a poor prognosis, partly due
      to the lack of a precise understanding of the molecular mechanisms associated
      with its malignant behavior. In the present study, we expanded on our previous
      studies on cell cycle control of MPM cells by targeting CD26 molecule with
      humanized anti-CD26 monoclonal antibody (HuCD26mAb), focusing particularly on
      ubiquitin-specific protease 22 (USP22). We showed that USP22 protein expression
      is detected in clinical specimens of MPM and that USP22 knockdown, as well as
      CD26 knockdown, significantly inhibits the growth and proliferation of MPM cells
      in vitro and in vivo. Moreover, depletion of both USP22 and CD26 suppresses MPM
      cell proliferation even more profoundly. Furthermore, expression levels of USP22
      correlate with those of CD26. HuCD26mAb treatment induces a decrease in USP22
      level through its interaction with the CD26 molecule, leading to increased levels
      of ubiquitinated histone H2A and p21. By demonstrating a CD26-related linkage
      with USP22 in MPM cell inhibition induced by HuCD26mAb, our present study hence
      characterizes USP22 as a novel target molecule while concurrently suggesting a
      new therapeutic strategy for MPM.

PMID- 30197003
TI  - Crystal structure of GSK3beta in complex with the flavonoid, morin.
AB  - GSK3beta is a key kinase that plays a role in cellular signaling pathways. In
      Alzheimer's disease (AD), GSK3beta has been implicated in hyperphosphorylation of
      tau proteins in the neuron, which is a hallmark of AD. Morin, a flavonoid that is
      abundant in nature, was found as an inhibitor of GSK3beta that can reduce tau
      pathology in vivo and in vitro. In this study, we determined the crystal
      structure of GSK3beta in complex with morin. The structure revealed that morin
      inhibits GSK3beta by binding to the ATP binding pocket. Our findings augment the
      potential of morin as a functional food to help prevent AD, as well as to provide
      structural information to develop new therapeutics based on the morin skeleton.

PMID- 30197004
TI  - Uncovering the underlying physical mechanism for cancer-immunity of MHC class I
      diversity.
AB  - The cancer cells are heterogeneous populated, which can be classified as MHC
      class I positive and MHC I class negative. They influence the immune system
      differently. In this work, we build a core cancer-immune circuit of MHC class I
      diversity including MHC class I positive cancer type, MHC I class I negative
      cancer type and 4 immune cell types to uncover the underlying mechanism of the
      cancer immunity based on the underlying landscape topography. We quantify four
      steady state attractors, normal state, two low cancer states and a high cancer
      state. The landscape topography changes upon changes in cancer self-activation
      and the related killing rate of the killer cells are illustrated. It demonstrates
      that the competition between the two cancer cell types. We simulate the
      tumorigenesis and development of cancer according to its biological process and
      classify these into 7 stages. This landscape framework provides a quantitative
      way to understand characteristics of these two cancer cell types under immune
      microenvironment and the underlying physical mechanisms of cancer cell evolution
      along cancer development.

PMID- 30197006
TI  - Fibroblast growth factor 21 attenuates hypoxia-induced pulmonary hypertension by
      upregulating PPARgamma expression and suppressing inflammatory cytokine levels.
AB  - Hypoxia-induced pulmonary hypertension (HPH) is a progressive disease
      characterized by a sustained, elevated pulmonary arterial pressure and vascular
      remodeling. The latter pathogenesis mainly involves overproliferation of
      pulmonary artery smooth muscle cells (PASMCs). Fibroblast growth factor 21
      (FGF21) has recently emerged as a novel regulator that prevents cardiac
      hypertrophic remodeling. However, its possible role in pulmonary remodeling
      remains unclear. The activation of peroxisome proliferator activated receptor
      gamma (PPARgamma) is reported to attenuate HPH by suppressing proliferative
      signals. Loss of PPARgamma in the lung contributes to abnormal proliferation of
      PASMCs. FGF21 is a key regulator of PPARgamma activity in adipocytes, but its
      role has not been elucidated in PASMCs. Therefore, we hypothesized that FGF21 may
      confer therapeutic effects in HPH by upregulating the expression of PPARgamma.
      Sprague-Dawley rats were exposed to hypoxia and treated with FGF21 for 4 weeks.
      In parallel, hypoxic conditions and FGF21 were administered to rat PASMCs for 48
      h. FGF21 attenuated the hypoxia-induced elevation in mean pulmonary arterial
      pressure (mPAP), right ventricular hypertrophy (RVH), medial thickening and
      overproliferation of PASMCs. Furthermore, FGF21 abrogated the reductions in
      PPARgamma expression and increases in TNF-alpha, IL-1 and IL-6 levels in PASMC
      culture media. Collectively, these results demonstrate that FGF21 could
      potentially attenuate the pathogenic derangements of HPH by targeting PPARgamma
      and inflammatory cytokines.

PMID- 30197005
TI  - Linkage between lipid droplet formation and nuclear deformation in HeLa human
      cervical cancer cells.
AB  - Because lipid droplets (LDs) and the nucleus are cellular organelles that
      regulate seemingly very different biochemical processes, very little attention
      has been focused on their possible interplay. Here, we report a correlation
      between nuclear morphology and cytoplasmic LD formation in HeLa human cervical
      cells. When the cells were treated with oleic acid (OA), LDs were formed in the
      cytoplasm, but not in the nucleoplasm. Interestingly, cells harboring OA-induced
      cytoplasmic LDs showed deformity of the nucleus, particularly at the nuclear rim.
      Conversely, when alteration from a single spherical nuclear shape to a
      multinucleated form was enforced by coadministration of paclitaxel and reversine,
      a significant amount of LDs was detected in the cytoplasm of the multinucleated
      cells. These two distinct pharmacological culture conditions not only allow
      analysis of the previously underappreciated organelle relationship, but also
      provide insights into the mutual affectability of LD formation and nuclear
      deformation.

PMID- 30197007
TI  - In vitro assessment of the acaricidal activity of carvacrol, thymol, eugenol and
      their acetylated derivatives on Rhipicephalus microplus (Acari: Ixodidae).
AB  - This study reports the comparative evaluation of the activity of carvacrol,
      thymol, eugenol and their respective acetylated derivatives (carvacrol acetate,
      thymol acetate and eugenol acetate) on Rhipicephalus microplus, to verify the
      possible influence of the acetate group. The acetylated derivatives were prepared
      from reactions of the phenolic compounds with acetic anhydride/pyridine. The
      formation of the products was confirmed by analysis of hydrogen and carbon-13
      nuclear magnetic resonance (1H and 13C NMR) spectra. The larval packet test was
      used to evaluate the acaricidal activity, with concentrations of 0.312, 0.625,
      1.25, 2.5, 5.0, 7.5, 10.0 and 15.0 mg/mL. Thymol and carvacrol resulted in 100%
      mortality starting at the concentration of 2.5 mg/mL, while the same was observed
      for carvacrol acetate starting at the concentration of 5.0 mg/mL. For the other
      treatments, 100% mortality was only achieved in the groups treated with the
      highest concentration (15.0 mg/mL). The LC50 and LC90 values (mg/mL) of carvacrol
      acetate (2.49, 4.21), thymol acetate (2.97, 8.52) and eugenol acetate (4.25,
      13.10) were higher than those for the corresponding precursor molecules carvacrol
      (0.83, 2.02), thymol (1.26, 2.21) and eugenol (2.77, 5.35). The acetylation
      process did not enhance the activity of these substances on unengorged larvae of
      R. microplus, since the precursor substances (carvacrol, thymol and eugenol) had
      greater efficacy.

PMID- 30197008
TI  - Molecular characterization and protective immunity of rhoptry protein 35 (ROP35)
      of Toxoplasma gondii as a DNA vaccine.
AB  - Toxoplasma gondii rhoptry proteins (TgROPs) have been considered the main targets
      and indicator molecules for immune diagnosis and prophylaxis because they present
      during the initial process of invasion. The aim of this study was to evaluate the
      protective effect of a TgROP35 DNA vaccine on experimental mice subjected to T.
      gondii challenge. The effect of intramuscularly injecting the genetic vaccine
      pVAX-ROP35 into BALB/c mice was evaluated, by first inserting the TgROP35
      sequence into the pVAX I eukaryotic expression vector. The levels of IgG, IgG1
      and IgG2a in pVAX-ROP35-vaccinated animals were integrally increased. Cytokine
      profile analyses revealed that IFN-gamma, IL-2 and IL-10 levels were
      significantly increased, while there were no significant differences in IL-4
      expression between the pVAX-ROP35 immunized and control groups. Additionally, we
      found that immunization with pVAX-ROP35 significantly prolonged the survival time
      (13.90 +/- 1.97 days) of mice after challenge infection with the virulent T.
      gondii RH strain compared with that in non-vaccinated control animals (mice died
      within 10 days). Moreover, the number of brain cysts (1450 +/- 287) in the
      animals subjected to pVAX-TgROP35 vaccination decreased remarkably (P <  0.05)
      compared to that in the blank control mice (2333 +/- 473). Furthermore, the size
      of brain cysts in the pVAX-TgROP35 group was significantly smaller than that in
      the blank control, PBS and pVAXI groups. The findings indicated that intense cell
      mediated and humoural immunity was triggered and that defence mechanisms against
      T. gondii were partially induced after vaccination by TgROP35.

PMID- 30197009
TI  - Renal azotemia and associated clinical and laboratory findings in dogs with
      Babesia rossi infection.
AB  - The occurrence of acute kidney injury in canine babesiosis is not well
      documented. Furthermore, interpretation of urine specific gravity (USG) to assess
      renal concentrating ability is hampered by the frequent presence of
      hemoglobinuria in this disease. This cross-sectional study aimed to test the
      hypothesis that renal azotemia (RA) is underdiagnosed according to current canine
      babesiosis literature by determining its occurrence at presentation, using urine
      osmolality instead of USG to measure urinary concentration. The second objective
      was to examine potential associations between the presence of RA and selected
      clinical and laboratory variables at presentation. Medical records available from
      3 previously performed prospective data collections were reviewed
      retrospectively. Client-owned dogs that were diagnosed with babesiosis caused by
      Babesia rossi, were included if a complete blood count, biochemistry profile, and
      urinalysis was performed at admission. Urine osmolality was measured to identify
      dogs with RA. Differences between dogs with RA and dogs without RA were assessed
      by nonparametric statistics. One hundred and fifty-two dogs were included, of
      which 26 (17%) were azotemic at admission. The occurrence of RA was 14% (21/152),
      hence 81% (21/26) of all azotemic dogs were diagnosed with RA. In contrast, when
      diagnosis of RA was based on an admission USG < 1.030, only 23% (6/26) of the
      azotemic dogs would have been considered to have RA. Several signalment and
      clinicopathological findings were found to be associated with the presence of RA,
      including older age, and the presence of collapse, hypoglycemia,
      hyperphosphatemia, cerebral babesiosis, and acute respiratory distress syndrome.
      Lastly, survival at discharge was significantly lower in dogs diagnosed with RA
      at presentation. Our results clarified that RA is more common than previously
      reported in B. rossi. This study also demonstrated that USG determination is not
      a reliable method to evaluate renal concentrating ability in azotemic dogs with
      babesiosis. Thus, if available, urine osmolality should be part of the diagnostic
      work-up of dogs infected with B. rossi to avoid misclassification of dogs with RA
      as having prerenal azotemia. If urine osmolality cannot be measured, clinicians
      should realize that most azotemic dogs with B. rossi infection have RA.

PMID- 30197010
TI  - Cryptosporidium infection is associated with reduced growth and diarrhoea in
      goats beyond weaning.
AB  - Cryptosporidium and Giardia are common parasites of ruminant livestock worldwide.
      These parasites are associated with diarrhoea outbreaks in young goats (pre
      weaning), but the impacts on health and productivity for older goats (post
      weaning) are not well understood. Here we show Cryptosporidium faecal shedding is
      associated with reduced growth and diarrhoea in goats aged approximately 9-15
      months. Goats were sampled four times at one-month intervals. Faecal shedding for
      a range of pathogens were determined using quantitative PCR and sequencing
      (Cryptosporidium, Giardia, Eimeria, Salmonella, Campylobacter), and microscopy
      (trichostrongylid nematode worm egg count and Entamoeba). Cryptosporidium faecal
      shedding was associated with 1.5 kg lower growth for the one-month period
      following sampling. Specifically, C. xiaoi was associated with 1.9 kg lower
      growth in the following month. This is the first report of production impacts
      associated with C. xiaoi in ruminants older than 3 months of age. Cryptosporidium
      shedding was associated with an over 4-fold increase in risk of diarrhoea, with
      C. parvum associated with 10-fold and C. ubiquitum associated with 16-fold
      increase in risk of diarrhoea. Notably, C. xiaoi shedding was not associated with
      increased risk of diarrhoea. Giardia shedding was associated with looser faecal
      consistency, but not diarrhoea. Higher Eimeria oocyst counts were weakly
      associated with lower live weight, poorer body condition and looser faecal
      consistency. Shedding of other enteric pathogens were not associated with impacts
      on live weight, growth or diarrhoea risk. This study challenges the two notions
      that Cryptosporidium infections only impact health and productivity of goats
      during the pre-weaning period, and that Cryptosporidium (and specifically C.
      xiaoi) infections in the absence of diarrhoea are asymptomatic. Recognising the
      potential for impacts of Cryptosporidium infection on growth rates in the absence
      of diarrhoea will support improved design for experiments testing impacts of
      Cryptosporidium on ruminant health and production. Improved understanding of the
      role of protozoan infections on animal health has implications for the management
      of goats in order to reduce adverse impacts on farm profitability, animal welfare
      and public health risk.

PMID- 30197011
TI  - Assessment of the effective dose of an experimental intramuscular formulation
      against immature and adult Fasciola hepatica in sheep.
AB  - The effective dose of an injectable prodrug, named compound alpha prodrug,
      against immature and adult Fasciola hepatica in experimentally infected sheep was
      determined. In a first experiment, 30 sheep were infected with Fasciola hepatica
      on day 0 and 50. After microscopic detection of faecal eggs on day 80, groups (n
      = 6) 1 to 3 were treated with 6, 8 and 10 mg/kg of the experimental water-soluble
      prodrug compound alpha intramuscularly, respectively. Group 4 was treated with
      closantel and group 5 remained untreated. Copromicroscopical examinations were
      made on day 0, 80 and 108. On day 110, trematodes were collected from the bile
      ducts. Fasciolicide efficacy was assessed as a percentage of fluke-egg and adult
      fluke reduction. Fluke length was also recorded. In a second experiment aimed to
      assess the fasciolicide activity of compound alpha prodrug against four-week-old
      flukes, 12 sheep were infected on day 0 and allocated into two groups (n = 6). On
      day 50 post infection, group A was treated with the experimental water-soluble
      prodrug compound alpha at 6 mg/kg/IM and B remained untreated. Fasciolicide
      activity was assessed on day 80 after collection, microscopic observation and
      measurement of flukes present in the parenchyma for immature stages and on day
      108 for adults. Egg output decreased 91.2, 96.0, 98.8 and 94.9% for groups 1, 2,
      3 and 4, respectively. Compound alpha prodrug cleared 97.6%, 98.51% and 100% of
      adult stages in a dose-dependent manner. Closantel killed 81.95% flukes.
      Regarding the second experiment, 81.2% efficacy was achieved. Immature flukes
      were significantly smaller in the treated group. It is concluded that the
      intramuscular application of compound alpha prodrug exerted fasciolicide efficacy
      against adults of Fasciola hepatica.

PMID- 30197012
TI  - Determination of the specific gravity of eggs of equine strongylids, Parascaris
      spp., and Anoplocephala perfoliata.
AB  - Given the ever-increasing levels of anthelmintic resistance in livestock
      parasites globally, it is recommended to use parasite fecal egg counts to make
      treatment decisions and to evaluate treatment efficacy. The consensus in equine
      parasitology is to use a flotation medium with a specific gravity (SG) of >= 1.20
      to float the main parasite egg types of interest in egg counting techniques.
      However, the density of common equine endoparasite eggs has been sparsely
      investigated. Equine tapeworm eggs are known to be particularly difficult to
      determine and count in fecal samples. It is unknown whether this could be because
      of differences in egg density. The aim of this study was to provide estimates of
      relative densities for equine ascarid, strongyle, and tapeworm eggs. Six aqueous
      glucose-salt solutions with specific gravities ranging from 1.06 to 1.16 were
      made and placed from most to least dense into thirteen 15 mL centrifuge tubes.
      Concentrated aqueous suspensions of the three types of endoparasite eggs were
      placed on top of each tube. These tubes were then centrifuged at 800 g for 20 min
      and each layer of flotation solution was carefully pipetted and transferred to a
      McMaster egg counting slide. Egg type and count were recorded for each specific
      gravity layer. Each egg was assigned a specific gravity based on the specific
      gravity layer it was observed in. In a second trial of this study, five similar
      flotation media were made ranging from 1.02 to 1.10 and were used in four
      subsequent replicates. In total between the two trials, the mean egg SGs of
      Anoplocephala perfoliata (n = 3811), Parascaris spp. (n = 3478), and strongylid
      type eggs (n = 9291) were 1.0636 (95% confidence interval (CI): 1.0629-1.0642),
      1.0903 (95% CI: 1.0897-1.0909), and 1.0453 (95% CI: 1.0448-1.0458), respectively.
      The three egg types were statistically different from each other (p < 0.0001).
      This is the first time that the specific gravity of equine strongylid and
      Anoplocephala perfoliata eggs has been determined. With a tapeworm egg density
      demonstrated to be between that of strongylids and Parascaris spp., the poor
      recovery of tapeworm eggs in equine fecal samples must have other explanations.

PMID- 30197013
TI  - Identification of third stage larval types of cyathostomins of equids: An
      improved perspective.
AB  - Cyathostomins comprise around 50 parasite species of equids, offering a great
      challenge regarding their individual identification. The objective of our work
      was to improve identification of infective third stage larvae (L3) with a
      morphological key supplemented with detailed scientific illustrations based on
      our research and available literature. The highlighted features were; the number,
      arrangement, and shape of intestinal cells (IC), general features and the total
      body length of the eight different Cyathostomin sensu latum types (Type A, B, C,
      D, E, F, G, H), Gyalocephalus capitatus, and Posteriostomum spp. Due to
      variability, we were unable to define final body length measurements to
      differentiate L3 of cyathostomins. However, IC characteristics displayed a higher
      difference between L3 types than total body length. Through the number and
      arrangement of IC, 14 species were classified within three larval types. The
      classification of L3 into distinct larval types sensu latum gives us the
      advantage of reducing the number of probable species presented in equine faecal
      samples using a low-cost technique when monitoring the parasite fauna present in
      individual horses or on the farm level. The present improved identification key
      shall increase the diagnostic capabilities of classical equine parasitology
      techniques, using general L3 morphology thereby pragmatically improving regional
      and transnational epidemiological and biodiversity studies. The present key may
      also assist in defining the cyathostomin community in cyathostominosis clinical
      cases and within drug resistant populations across different management systems
      and geographical locations.

PMID- 30197014
TI  - Corrigendum to "Larval development of Aelurostrongylus abstrusus in
      experimentally infected Rumina decollata snails" [Vet. Parasitol. 251 (2018) 50
      55].

PMID- 30197015
TI  - Development and validation of direct dry loop mediated isothermal amplification
      for diagnosis of Trypanosoma evansi.
AB  - Non-tsetse transmitted Trypanosoma evansi infection (Surra) is one of the most
      important diseases of camels in north and east Africa and of buffalo and cattle
      in Asia. Early, accurate and feasible diagnosis is a crucial step towards the
      control of Surra. Dry format of loop-mediated isothermal amplification (LAMP)
      diagnostics for the detection of T. evansi was developed, where the detection
      limit was determined as to equivalent to one parasite per reaction. The assay was
      validated by testing blood from 48 camels clinically diagnosed to have Surra,
      which all tested negative microscopically and revealed 43 (89.6%) to be positive
      for T. evansi when tested by the dry-LAMP. Furthermore, DNA extracted from a
      randomly selected subset of 20 of these blood samples were then subjected to
      RoTat1.2-PCR (TaKara Ex Taq), with 14 matching results, with six that were
      positive by dry-LAMP and negative by PCR. The kappa value of dry-LAMP applied to
      direct blood was 0.4211, indicating moderate agreement to RoTat 1.2-PCR. In
      addition, 103 genomic DNA extracted from camels' blood were tested by both dry
      LAMP and RoTat1.2-PCR revealed 67 matching results and 31 positive by dry-LAMP
      and negative by PCR and a further five positives by PCR and negative by dry-LAMP.
      This novel dry-LAMP method is more sensitive than conventional PCR, direct
      (without DNA extraction step), is user friendly and does not require cold chain
      or highly trained personnel.

PMID- 30197016
TI  - Influence of selective treatment of bulls on the infestation of Haematobia
      irritans on untreated cows.
AB  - The distribution of Hematobia irritans is not homogeneous in cattle populations.
      Generally, between 15% and 30% of bovines carry more than 50% of the flies, and
      higher infestations occur in bulls. In this study, the effect of treating the
      bulls with ear tags containing 40% diazinon on the infestation of flies on the
      herd during the breeding season was evaluated. Four groups of cattle were made,
      each containing one bull and 35 Braford cows. Groups 1 and 2 were on pastures in
      highlands. Groups 3 and 4 were on pastures in lowlands. At the beginning of the
      trial, each bull from Groups 1 and 3 was treated with an ear tag. Bulls from
      Groups 2 and 4 remained untreated. Weekly, for 10 weeks, horn flies were counted
      from each bull and 15 cows from each group. A repeated measures linear mixed
      model was used with cows as random effects. The number of horn flies in the
      treated groups was lower than that in the untreated group, suggesting that
      selective treatment of bulls could be an effective strategy to control horn flies
      on the herd. The number of flies was higher in the lowland than that in the
      highland groups, suggesting an effect of the environment on horn fly
      infestations. In addition, we estimated the cow level predictions from the model
      to estimate the cow effect on fly counts, and we compared those values with the
      observed weekly quartiles for each group. Fly-susceptible cows were defined as
      those for which the infestation of flies appeared in the upper quartile more than
      50% of the weeks and in the lower quartile less than 20% of the weeks. In
      contrast, a fly-resistant cow was defined as one for which the fly counts
      appeared in the lower quartile more than 50% of the weeks and in the upper
      quartile less than 20% of the weeks. In all, 8.3% of the cows were susceptible
      and 15% were resistant. These results may be used to selectively treat bulls or
      to treat the bulls and the most susceptible cows during the breeding season.

PMID- 30197017
TI  - The use of the larval development assay for predicting the in vivo efficacy of
      levamisole against Haemonchus contortus and Trichostrongylus colubriformis.
AB  - The larval development assay has been used for many years to measure the
      sensitivity of the free-living life stages of trichostrongylid nematodes to
      anthelmintics. The assay has applications in both drug discovery and the
      diagnosis of drug resistance. We revisited the usefulness of the larval
      development assay for diagnosis of resistance to levamisole using field-derived
      isolates of Haemonchus contortus and Trichostrongylus colubriformis showing
      varying levels of resistance to this drug in vivo. Each of the resistant isolates
      showed a plateau in their larval development assay dose-response at the highest
      drug concentrations tested, representing a highly-resistant fraction, amounting
      to between 6.9 and 55.1% of the populations. The remaining population fractions
      for the resistant isolates showed IC50 values from 1.4- to 17.8-fold higher than
      their corresponding susceptible isolate of the same species. We used a data set
      from the DrenchRite(r) test user manual to derive equations describing the
      relationship between the IC50 values for these low / moderate resistance
      components of each population and in vivo drug efficacy, and then used these
      equations to estimate the expected in vivo efficacy of levamisole against this
      population component of each isolate. A combination of this expected efficacy,
      with the known zero efficacy of the drug in vivo against the highly-resistant
      population fractions in each isolate, allowed us to calculate a predicted drug
      efficacy for the whole population for each isolate. The predicted levamisole
      efficacies for the three resistant H. contortus isolates were 88.8, 84.1 and
      43.7%. These compared favourably with the actual efficacy of the drug against
      these isolates as determined in faecal egg count reduction tests or total worm
      count studies: 79, 66.3 and 40.6%, respectively. Similarly, for T. colubriformis,
      predicted efficacies of 82.0 and 1.8% compared favourably with the actual
      efficacies of 65-92 % and 0%, respectively. This study illustrates the usefulness
      of the larval development assay as a diagnostic tool for predicting in vivo
      efficacy of levamisole against H. contortus and T. colubriformis.

PMID- 30197018
TI  - Relationship between serum anti-Leishmania antibody levels and acute phase
      proteins in dogs with canine leishmaniosis.
AB  - This study examined the relationship between two serologic assays which quantify
      anti-Leishmania antibodies (a commercial enzyme-linked immunosorbent assay
      (ELISA) and a time-resolved immunofluorometric assay (TR-IFMA)) and selected
      acute phase proteins (APPs) and analytes related to protein concentration. Data
      were obtained from 205 canine serum samples from different veterinary clinics
      located in an area in which canine leishmaniosis (CanL) is endemic. The samples
      were submitted to the Interdisciplinary Laboratory of Clinical Analysis (Interlab
      UMU), University of Murcia, Spain, for analysis. The biochemical analytes
      evaluated were serum ferritin, C-reactive protein (CRP), haptoglobin, paraoxonase
      1 (PON-1) and albumin as APPs and total proteins and globulins as indicative
      analytes of protein concentration. Samples were submitted for the initial
      diagnosis of CanL, or to monitor the response to treatment in patients with CanL.
      The evaluation of the biochemical analytes did not show differences between
      Leishmania-seronegative and Leishmania-seropositive dogs. However, dogs with high
      antibody titers showed more pronounced clinicopathological abnormalities. Both
      serological assays had correlations of different significance with the
      biochemical analytes, showing higher significant correlations with total proteins
      and globulins than with the rest of the analytes. When the samples submitted for
      diagnosis and treatment monitoring were analyzed separately, serological assays
      showed lower correlation in samples for treatment monitoring (r = 0.531, p < 
      0.0001) than in samples for diagnosis (r = 0.769, p <  0.0001). In addition,
      higher correlations were found between TR-IFMA and analytes such as serum
      ferritin and CRP in the treatment monitoring group than with the ELISA. These
      results may help to clarify the relationship between anti-Leishmania antibody
      levels and selected biochemical analytes related to inflammation and protein
      concentration in CanL.

PMID- 30197019
TI  - French guidelines for the outpatient management of Ebola virus disease:
      Applicability by family physicians.
AB  - BACKGROUND: During the last alarming Ebola Virus Disease (EVD) outbreak, the
      French Ministry of Health developed guidelines for the outpatient management of
      EVD. We aimed to assess family physicians' (FP) knowledge of EVD, to assess their
      working conditions, and to collect their opinion about the applicability of these
      guidelines in France. METHODS: Cross-sectional quantitative study (telephone or
      email) performed (November 2014-June 2015) during the EVD outbreak. Relevant
      results were further analyzed with a qualitative study (interviews) based on
      grounded theory (June-September 2016), after the end of the EVD outbreak.
      RESULTS: Thirty-three FPs out of 100contacted answered our survey (response rate:
      33%). We interviewed five FPs. Their knowledge of EVD was good. Information sent
      by post, especially from the national medical association, was considered the
      best means of information and was preferred to emails. Compliance with guidelines
      was based on their ease of understanding and application (common sense). The main
      difficulty in applying these guidelines was the unusual recommended equipment
      that seemed unnecessary as the management of these patients was based on their
      interview (anamnesis) and isolation without examination. EVD had little impact on
      the FPs' practice, they only trained their secretaries to screen for suspected
      EVD patients and refer them to the mobile emergency unit. CONCLUSION: FPs had
      good knowledge of EVD and guidelines. This seemed important to prevent the
      outbreak in France as they were ready to cope with such a situation, thanks to
      guidelines they could easily adjust to their practice.

PMID- 30197020
TI  - Large artery stiffness according to different assessment methods in adult
      population of St.Petersburg.
AB  - OBJECTIVE: The aim of the present study was to assess the prevalence of increased
      arterial stiffness by different diagnostic methods and its association with
      cardiovascular risk in Russian population-based cohort. DESIGN AND METHODS: In
      terms of Russian epidemiological study ESSE-RF a random selection of 452
      apparently healthy Saint-Petersburg inhabitants aged 25-65 years was performed.
      Fasting lipids, glucose and blood pressure measurements were performed. We used 3
      diagnostic methods of arterial stiffness assessment: pulse wave velocity by
      applanation tonometry (SphygmoCor - PWV-S) and pulse wave velocity by volumetric
      sphygmography (VaSera - PWV-V), and cardio-ankle vascular index (CAVI) by VaSera.
      RESULTS: 341 (75,4%) had normal parameters of arterial stiffness assessed by all
      methods. Spearmen's coefficient of correlation and "kappa" coefficient for PWV-S
      and CAVI were 0,74 and 0,04, for PWV-S and PWV-V - 0,10 and 0,06, for CAVI and
      PWV-V - 0,28 and 0,03, respectively. There was a significant correlation between
      cardiovascular risk (defined by SCORE) and PWV-S (r = 0,38, p < 0,001) and a non
      significant trend of increasing CAVI along with cardiovascular risk (r = 0,35, p
      = 0,14). CONCLUSIONS: Different methods of arterial stiffness assessment showed a
      weak correlation with each other. Carotid-femoral pulse wave velocity detected by
      applanation tonometry is associated with high cardiovascular risk score and might
      be considered as better additional risk marker for cardiovascular risk
      stratification.

PMID- 30197021
TI  - Making a case for routine high resolution ultrasonography (HRUSG) of thyroid in
      Graves' disease.

PMID- 30197022
TI  - Burnout and gender in surgical training: A call to re-evaluate coping and
      dysfunction.
AB  - BACKGROUND: Physicians experience burnout and mental illness at significantly
      higher rates than the general population, with sequelae that negatively affect
      providers, patients, and the healthcare system at large. Gender is rarely
      considered in characterizing the problem or vetting interventions. METHODS: Using
      data from a recent national survey and a longitudinal pilot study of general
      surgery residents, we examined gender variation in burnout and distress. RESULTS:
      In the national survey, male residents had higher depersonalization and female
      residents had higher alcohol misuse, with a significant association between
      alcohol misuse, high depersonalization and low anxiety not seen in males. In the
      longitudinal pilot study, males' burnout scores were higher and had a greater
      contribution from depersonalization. Both males and females had increasing
      prevalence of high depersonalization over the intern year. CONCLUSIONS: Residency
      affects males and females differently in ways that merit further investigation
      and better understanding to effectively address burnout and distress.

PMID- 30197023
TI  - AMSC-derived exosomes alleviate lipopolysaccharide/d-galactosamine-induced acute
      liver failure by miR-17-mediated reduction of TXNIP/NLRP3 inflammasome activation
      in macrophages.
AB  - BACKGROUND: Mesenchymal stem cell (MSC)-derived exosome administration has been
      considered as a novel cell-free therapy for liver diseases through cell-cell
      communication. This study was aimed to determine the effects and mechanisms of
      AMSC-derived exosomes (AMSC-Exo) for acute liver failure (ALF) treatment.
      METHODS: AMSC-Exo were intravenously administrated into the mice immediately
      after lipopolysaccharide and D-galactosamine (LPS/GalN)-exposure and their
      effects were evaluated by liver histological and serum biochemical analysis. To
      elucidate its mechanisms in ALF therapy, the expression levels of miRNAs and
      inflammasome-related genes in macrophages were evaluated by qPCR and Western blot
      analysis, respectively. The exosomes from miR-17-knockdowned AMSCs (AMSC-ExomiR
      17-KD) were used for further determine the role of miR-17 in AMSC-Exo-based
      therapy. FINDINGS: AMSC-Exo administration significantly ameliorated ALF as
      determined by reduced serum alanine aminotransferase and aspartate
      aminotransferase levels and hepatic inflammasome activation. Further experiments
      revealed that AMSC-Exo were colocalized with hepatic macrophages and could reduce
      inflammatory factor secretion by suppressing inflammasome activation in
      macrophages. Moreover, miR-17, which can suppress NLRP3 inflammasome activation
      by targeting TXNIP, was abundant in AMSC-Exo cargo. While, the therapeutic
      effects of AMSC-ExomiR-17-KD on ALF were significantly abolished as they could
      not effectively suppress TXNIP expression and consequent inflammasome activation
      in vitro and in vivo. INTERPRETATION: Exosome-shuttled miR-17 plays an essential
      role in AMSC-Exo therapy for ALF by targeting TXNIP and suppressing inflammasome
      activation in hepatic macrophages. AMSC-Exo-based therapy may present as a
      promising approach for TXNIP/NLRP3 inflammasome-related inflammatory liver
      diseases. FUND: Key R&D projects of Zhejiang province (2018C03019) and National
      Natural Science Fund (81470851 and 81500616).

PMID- 30197024
TI  - [Multidisciplinary consultation for patients with HPV-related invasive carcinoma
      or precancerous lesions].
AB  - Given the recent increase in the number of human papillomavirus (HPV)-induced
      cancers in other locations than gynaecological, the number of patients with two
      cancers at distinct sites, and because of the lack of exhaustive data, we decided
      to create a multidisciplinary network around an HPV consultation at the Georges
      Pompidou European Hospital (HEGP). This network aims to set up the best tools for
      detecting HPV-associated "multisite" precancerous lesions in order to determine
      the possible impact of dedicated care for this at-risk population. This monthly
      consultation was created at the HEGP in June 2014. It is currently organized
      around five consultations: gynaecological, ENT, urological, digestive and
      immunological. Every patient who has been diagnosed with HPV-related cancer and
      whose care is provided at the HEGP is offered this particular follow-up:
      systematically, once the initial lesion has been treated, the patient is convened
      annually for a day during which it benefits from the consultations mentioned
      above. A consultation with a psychologist is systematically proposed. Local
      samples are taken at each site: a cytological examination, the analysis of known
      predictive and prognostic virological markers are carried out. This study fits
      more broadly in a theme of clinical and fundamental research around cancers
      related to HPV.

PMID- 30197025
TI  - [Hypofractioned radiotherapy in elderly patient with glioblastoma].
AB  - Glioblastoma is the most frequent primary brain tumor, with more than half of all
      patients being at least 65 years old. The treatment of the elderly in this
      pathology represents therefore a considerable challenge for oncologists and
      radiation therapists. However, in most clinical trials, age is a non-eligible
      criterial. In the last ten years, geriatric therapeutic trials have been
      multiplied. The treatment of glioblastoma consists of adjuvant chemoradiotherapy.
      In elderly patients, the evaluation of performans status and the molecular
      characteristics of the tumor are important factors in order to propose the
      appropriate treatment in terms of efficacy and toxicity.

PMID- 30197026
TI  - Combining radiation therapy and cancer immune therapies: From preclinical
      findings to clinical applications.
AB  - Besides its direct cytotoxic effect on the tumor cells, radiation therapy is also
      able to elicit an immune-mediated systemic anti-tumor response, resulting in
      tumor regression in irradiated sites but also within distant out of field
      secondary lesions and providing a long-term anti-tumor response. It is now clear
      that associating ionizing radiation with immune therapies can enhance radio
      induced anti-tumor immune responses. Over the last decade, such a combination
      aroused considerable interest among the scientific community, with many
      preclinical models and clinical trials, using many types of immune therapies and
      radiation regimens. In this article, we summarize the main mechanisms underlying
      radio-induced anti-tumor responses. We will then present an extended overview of
      the recent preclinical and clinical research built on this background of combined
      radiation and immune therapy, shedding light on what we know so far about such a
      promising strategy.

PMID- 30197028
TI  - Nutritional considerations in the care of conjoined twins.
AB  - Conjoined twins represent an interesting nutritional challenge as nutrient
      delivery and absorption is greatly affected by anatomy and, therefore, unique to
      each twin pair. Nutritional support is essential to optimize growth and
      development in the neonatal period; however, very little data exists on the topic
      in this population. Conjoined twins require individualized nutritional assessment
      that focuses on the interaction between the metabolic rate, nutrient uptake, and
      nutrient delivery of each twin in the dyad. This report describes one center's
      experience with monitoring growth, establishing nutrient requirements, and
      determining substrate utilization in three sets of conjoined twins.

PMID- 30197027
TI  - [Prevalence and expectations of "alternative and complementary medicine" use
      during radiotherapy in 2016: A prospective study].
AB  - PURPOSE: Alternative and complementary medicine is defined as any substance or
      technique of non-allopathic medicine used to improve health and quality of life.
      The purpose of this prospective observational study was to evaluate the use of
      alternative and complementary medicine during radiotherapy. MATERIAL AND METHODS:
      A questionnaire was given the last week of treatment to all patients treated for
      breast cancer, prostate cancer or head and neck cancer in our centre in 2016.
      RESULTS: In 2016, 132 patients were included. Fifty-seven patients (43%) used
      alternative and complementary medicine during radiotherapy, more women (61%) than
      men (35%) (P=0.005). The use of alternative and complementary medicine varied
      according to locations: 44% of head and neck cancers, 57% of breast cancers and
      24% of prostate cancers, but sex was the confounding factor. If alternative and
      complementary medicine was used before radiotherapy, 82% of patients used it
      during treatment, compared to 30% if they were naive (P<10-7). Healing touch
      (68%), homeopathy (26%) and magnetisers (21%) were the most used alternative and
      complementary medicines. Sixty-one percent of patients used alternative and
      complementary medicine to reduce skin and mucosal side effects of treatments, 28%
      to improve well-being, and 9% to treat cancer. Seventy-two percent of all
      patients would advise their loved one to use an alternative and complementary
      medicine and 87% would like information about them in the hospital. CONCLUSION:
      Alternative and complementary medicines are used more by women, and by patients
      who used them before radiotherapy. The desired effects are mainly to reduce the
      side effects of the treatments. More than 80% of patients, whether or not they
      use alternative and complementary medicine, demand medical information.

PMID- 30197029
TI  - Synthesis and biological evaluation of novel 5,6-dihydropyrimido[4,5
      f]quinazoline derivatives as potent CDK2 inhibitors.
AB  - As serine/threonine kinase, the cyclin dependent kinase 2 (CDK2) is a promising
      target for various diseases such as cerebral hypoxia, cancer, and
      neurodegenerative diseases. Here we reported the structure-based synthesis and
      biological evaluation of novel 5,6-dihydropyrimido[4,5-f]quinazoline derivatives
      as CDK2 inhibitors, which exhibited potent CDK2 inhibitory activities, as well as
      anticancer activities in low concentration against two human cancer cell lines
      (MCF-7 and HCT116). In particular, compounds 11a and 11f (IC50 values of 0.11 and
      0.09 MUM for CDK2, respectively) have demonstrated significantly inhibitory
      potency against CDK2 and have showed great inhibitory activities against MCF-7
      and HCT116 cell lines.

PMID- 30197030
TI  - (E)-N-Aryl-2-oxo-2-(3,4,5-trimethoxyphenyl)acetohydrazonoyl cyanides as tubulin
      polymerization inhibitors: Structure-based bioisosterism design, synthesis,
      biological evaluation, molecular docking and in silico ADME prediction.
AB  - A series of (E)-N-Aryl-2-oxo-2-(3,4,5-trimethoxyphenyl)acetohydrazonoyl cyanides
      have been synthesized and evaluated for their anticancer activity in human
      hepatocellular liver carcinoma HepG2 and breast adenocarcinoma MCF-7 cell lines.
      Among all the tested compounds, compound 3a, 3e and 3n displayed more activity
      than lead compound with IC50 value of 0.26-0.61 MUM. Meanwhile, these compounds
      (3a, 3e and 3n) showed potent antiproliferative activity against a panel of
      cancer cells and the HCT-8/T multidrug resistant cell line with IC50 values in
      the range of 0.077- 7.44 MUM. Flow cytometric analyses revealed that compound 3n
      induced cell cycle arrest in G2/M phases in a dose dependent manner. The compound
      3n also displayed potent tubulin polymerization inhibition with an IC50 value of
      0.9 uM, with ten folds more active than colchicine (IC50 = 9 MUM). Molecular
      docking studies revealed that compound 3n efficiently interacted with the
      colchicine binding site of tubulin through hydrophobic, cation-pi and hydrogen
      bond interaction. Furthermore, in silico pharmacokinetic prediction shown that
      these compounds have a good ADME-related physicochemical parameters. These
      results demonstrate that 3n exhibits potent cytotoxicity in cancer cells by
      targeting the colchicine binding site of tubulin and potentially acts as a
      therapeutic lead compound for the development of anticancer drugs.

PMID- 30197031
TI  - Breathlessness catastrophizing relates to poorer quality of life in adults with
      cystic fibrosis.
AB  - BACKGROUND: Cystic Fibrosis (CF) is the most common genetic disease affecting
      children and young adults in Canada. It is a multi-system disease, however lung
      disease is largely responsible for mortality. Treatment advances have resulted in
      increased life expectancy and a subsequent need to better understand psychosocial
      issues associated with quality of life in adults living with CF. Emerging
      research suggests that anxiety and depression are related to poorer health
      related quality of life (HRQoL) in CF patients, but there is little research
      examining cognitive processes, such as breathlessness catastrophizing. The
      present study addresses this gap in the literature. METHODS: Participants in this
      study are based on a convenience sample of patients recruited during their
      regular CF clinic appointments at a tertiary care center. Forty-five adults (Mage
      = 30.73 years) completed measures of lung function, depression, anxiety, pain,
      breathlessness catastrophizing, and HRQoL at one time point. RESULTS: Results of
      a hierarchical multiple regression indicate that increased breathlessness
      catastrophizing was related to poorer HRQoL, after controlling for lung function,
      depression, anxiety, and pain (p < .05). Depression, pain, and breathlessness
      catastrophizing all emerged as significant unique predictors of HRQoL.
      CONCLUSIONS: Breathlessness catastrophizing is a potential target for clinical
      intervention and might impact HRQoL. Further research on breathlessness
      catastrophizing in CF is warranted including longitudinal studies to examine the
      mechanisms by which breathlessness catastrophizing relates to HRQoL and treatment
      outcomes in CF.

PMID- 30197032
TI  - Development and psychometric validation of a novel measure of sensory
      expectancies associated with E-cigarette use.
AB  - INTRODUCTION: E-cigarette dependence measures largely focus on e-cigarette use
      ("vaping") that is linked to nicotine use, and measures assessing sensory aspects
      of vaping that may influence use (e.g., taste) are limited in scope. Thus, we
      developed the novel Sensory E-cigarette Expectancies Scale (SEES). METHODS: In
      Summer 2017, 610 adult e-cigarette users (48.7% male, 84.9% White, 37.41[+/
      12.15] years old) completed an online survey that included 23 SEES items.
      Psychometric analyses included evaluating latent structure, internal consistency,
      measurement invariance, mean differences, and test-criterion relationships.
      RESULTS: Factor analyses supported a 9-item, 3-subscale structure (taste/smell,
      pleasure/satisfaction, vapor cloud production). Subscales evidenced internal
      consistency and scalar invariance by sex, race, smoking status (current/not),
      vaping status (daily/not), e-liquid nicotine content (yes/no), and device type
      (cig-a-likes/vape-pens/Advanced Personal Vaporizers [APVs]/Mods). Women and daily
      e-cigarette users reported stronger SEEs for taste/smell and pleasure than their
      counterparts. Non-white participants reported stronger SEEs for cloud production
      than White participants. Cig-a-like users reported the weakest SEEs for
      taste/smell and weaker SEEs linked to cloud production than APV/mod users. SEES
      scores evidenced convergence with nicotine dependence (mean r = .36). Finally,
      SEES scores predicted vaping frequency and habitual vaping concurrently and
      incrementally beyond nicotine dependence. CONCLUSIONS: The SEES evidenced good
      psychometric properties, suggesting that the measure can be used to assess
      sensory vaping expectancies in adults. Importantly, SEES scores indicated that
      sensory expectancies are related, yet distinct, from nicotine dependence. Future
      research should evaluate how SEEs relate to product characteristic preferences
      and patterns of vaping including the development and maintenance of addiction.

PMID- 30197033
TI  - Variant morphology and arterial supply of diaphragmatic crura with probe patent
      foramen ovale.
AB  - Crura are the posterior pillars of the tendino-muscular partition between
      thoracic and abdominal cavity. This study highlights bilaterally an unfamiliar
      morphology of diaphragmatic crura with uncommon origin of inferior phrenic artery
      and accompanying atrial septal defect in a 63-years-old female cadaver with
      scoliosis. An attempt is made to portray the clinical implications of these
      variations. In addition authors have discussed the embryological and genetic
      basis of these variations. In the recent few decades, surgical correction of
      scoliosis involving intervention with the crura has gained pace. Knowledge about
      the normal as well as variant crural morphology is imperative for the surgeons to
      decide the correct approach during spinal corrective surgeries and for
      radiologist to prevent any diagnostic pitfall. Familiarity about the variant
      origin of inferior phrenic artery may prevent complications during treatment of
      pathological conditions related to inferior phrenic artery. Preoperative
      awareness about the coexisting atrial septal defect is vital for
      anesthesiologists promoting them to administer cardioprotective anesthetic drugs.
      To the best of our knowledge, description of such a combination of variations in
      anatomical literature is rare and scarcely reported. Awareness of these
      anatomical variations is relevant for operating surgeons, radiologists,
      anesthesiologists and anatomists.

PMID- 30197034
TI  - A 3D characterization method of geometric variation in edentulous mandibles.
AB  - PURPOSE: The aim of this study was to perform an exploratory analysis of the
      morphological variations of mandibles at diverse states of edentulousness using
      tridimensional geometric morphometrics. METHODS: Twelve cadaveric mandibles were
      selected and divided in three groups: dentate (G1), partially edentate (G2) and
      totally edentate (G3). CT scans, segmentation and digital reconstruction of 3D
      surfaces of each specimen was made. Thirteen landmarks were defined; the
      measurement error was determined and 3D morphometrics exploratory analysis by
      principal components (PCs) and PC scores was performed. RESULTS: The principal
      shape variations in G2 and G3 compared to G1 can be summarized as follows: (1)
      decrease in the mid body mandibular height of 24% in G2 and 41% in G3, (2)
      decrease of symphysis height of 16% in G2 and 37% in G3, (3) a decrease in
      posterior mandibular height of 30% in both G1 and G2, (4) a deeper sigmoid notch
      also in both groups and finally (5) a widening of 7.7% in the cross sectional
      morphology on the symphysis in G3. CONCLUSIONS: The 3D morphometric methods,
      combined with surface morphing tools confirmed the main patterns of bone changes
      in edentulous mandibles, referenced in the literature. The average 3D mandibular
      morphologies of each edentulousness state group was also defined. These methods
      could offer more accurate definition of shape variations, which is critical in a
      clinical context. This study provides clinicians with highlights of 3D
      morphological mandibular variations at different states of edentulism and not
      only in 2D projections as they are currently described. The 3D surface model for
      each group in PDF3D file format, are include in supplementary material.

PMID- 30197035
TI  - Varian Halcyon dosimetric comparison for multiarc VMAT prostate and head-and-neck
      cancers.
AB  - The Varian Halcyon linear accelerator is designed for faster treatment time and
      fewer treatment errors than conventional linear accelerators. Its increased
      gantry speed (4 rpm), dose rate (800 MU/min), and leaf speed (5 cm/s) reduce
      treatment time. The 2 multileaf collimator banks of 1 cm leaf width could cause
      planning difficulties, but utilizing many arcs could address this challenge.
      While 3 or more arcs are often avoided due to the increased treatment time, the
      Halcyon can deliver 5 arcs in under 3 minutes. For prostate and head-and-neck, we
      hypothesized plan quality would increase with increasing arcs without
      compromising treatment time. Fifteen prostate and fifteen head-and-neck
      previously treated patients were replanned to 78 and 66 Gy, respectively. A total
      of 150 volumetric modulated arc therapy (VMAT) plans, ranging from 1 to 5 arcs,
      were created to compare organ-at-risk (OAR) sparing, target coverage,
      homogeneity, and hotspot volume. Plans were normalized to the prescribed dose of
      98% and 95% of the primary target volume for prostate and head-and-neck,
      respectively. All prostate 4-arc and 5-arc plans met MD Anderson Cancer Center
      (MDACC) constraints, while 86.7%, 20%, and 6.7% of the 1-arc, 2-arc, and 3-arc
      plans did not meet constraints, respectively. As the number of arcs increased,
      all OAR maximum doses decreased. All head-and-neck 5-arc plans met MDACC
      constraints, while 73.3%, 26.7%, 13.3%, and 6.7% of the 1-arc, 2-arc, 3-arc, and
      4-arc plans did not meet constraints, respectively. The contralateral parotid
      mean dose and the spinal cord maximum dose decreased with increasing arcs.
      Homogeneity and conformity indices decreased when increasing from 1 to 5 arcs for
      both prostate and head-and-neck. Overall, homogeneity and conformity indices and
      OAR doses improved when using three or more arcs. Therefore, using at least 3
      arcs for VMAT plans on the Halcyon will increase plan quality without
      compromising treatment time.

PMID- 30197036
TI  - Trypanosomatid Deoxyhypusine Synthase Activity Is Dependent on Shared Active-Site
      Complementation between Pseudoenzyme Paralogs.
AB  - Trypanosoma brucei is a neglected tropical disease endemic to Africa. The
      polyamine spermidine is essential for post-translational hypusine modification of
      eukaryotic initiation factor 5A (eIF5A), which is catalyzed by deoxyhypusine
      synthase (TbDHS). In trypanosomatids, deoxyhypusine synthase (DHS) activity is
      dependent on heterotetramer formation between two paralogs, DHSc and DHSp, both
      with minimal activity on their own due to missing catalytic residues. We
      determined the X-ray structure of TbDHS showing a single functional shared active
      site is formed at the DHSc/DHSp heterodimer interface, with deficiencies in one
      subunit complemented by the other. Each heterodimer contains two NAD+ binding
      sites, one housed in the functional catalytic site and the second bound in a
      remnant dead site that lacks key catalytic residues. Functional analysis of these
      sites by site-directed mutagenesis identified long-range contributions to the
      catalytic site from the dead site. Differences between trypanosomatid and human
      DHS that could be exploited for drug discovery were identified.

PMID- 30197038
TI  - Propagated Perturbations from a Peripheral Mutation Show Interactions Supporting
      WW Domain Thermostability.
AB  - Inter-residue interactions stabilize protein folds and facilitate allosteric
      communication. Predicting which interactions are crucial and understanding why
      remain challenging. We highlight this through studies of a single peripheral
      mutation (Q33E) on the surface of the Pin1 WW domain that causes an unexpected
      loss of thermostability. Nuclear magnetic resonance studies attribute the loss to
      reorganizations of electrostatic and hydrophobic interactions, resulting in
      propagated conformational perturbations. The propagation demonstrates the
      cooperative response of Pin1 WW to external perturbations, consistent with its
      allosteric behavior within Pin1. Microsecond molecular dynamics simulations
      suggest the wild-type fold relies on couplings between a surface electrostatic
      network and a highly conserved hydrophobic core; Q33E directly perturbs the
      former, thereby disrupting the latter. These couplings suggest that predictions
      of mutation consequences that assume dominance of a single interaction type can
      be limiting, and highlight challenges in predicting protein mutational
      landscapes.

PMID- 30197037
TI  - Insights into Kinesin-1 Activation from the Crystal Structure of KLC2 Bound to
      JIP3.
AB  - Kinesin-1 transports numerous cellular cargoes along microtubules. The kinesin-1
      light chain (KLC) mediates cargo binding and regulates kinesin-1 motility. To
      investigate the molecular basis for kinesin-1 recruitment and activation by
      cargoes, we solved the crystal structure of the KLC2 tetratricopeptide repeat
      (TPR) domain bound to the cargo JIP3. This, combined with biophysical and
      molecular evolutionary analyses, reveals a kinesin-1 cargo binding site, located
      on KLC TPR1, which is conserved in homologs from sponges to humans. In the
      complex, JIP3 crosslinks two KLC2 TPR domains via their TPR1s. We show that TPR1
      forms a dimer interface that mimics JIP3 binding in all crystal structures of the
      unbound KLC TPR domain. We propose that cargo-induced dimerization of the KLC TPR
      domains via TPR1 is a general mechanism for activating kinesin-1. We relate this
      to activation by tryptophan-acidic cargoes, explaining how different cargoes
      activate kinesin-1 through related molecular mechanisms.

PMID- 30197039
TI  - Criticality of the measurement of corneal thickness in specular reflection by
      digital biomicroscope.
AB  - PURPOSE: The aim was to evaluate the effects on corneal thickness (t)
      measurement, of asymmetry of the CCD position for a digital biomicroscope in
      specular reflection. METHODS: t was deduced from the distance between reflexes
      from anterior and posterior corneal surfaces using a biomicroscope (Takagi SM70
      N), with the illuminator either, (a) farther from sensor side (150 eyes) or, (b)
      closer to it (134 eyes). The distance between reflexes was also measured on a
      glass slide and a reference lens, with nominal thicknesses of 1580 and 520 MUm,
      respectively. Corneal thickness (tPACH) was also measured by pachymeter (Canon TX
      20 P). RESULTS: When biomicroscope asymmetry was ignored, t for the glass slide
      was (a) 1760 and (b) 1404 MUm. Correcting for the asymmetry provided
      corresponding values of 1588 and 1591 MUm. For the lens, t was (a) 696 and (b)
      543 MUm, or 642 and 497 MUm, when using the approximation of parallel surfaces
      (APS). Correcting for the asymmetry gave 565 and 552 MUm (578 and 564 MUm, with
      APS). Mean corneal t was (a) 560 and (b) 467 MUm, (564 and 468 MUm, with APS).
      Correcting for asymmetry gave (a) 506 and (b) 529 MUm (508 and 530 MUm, with
      APS). Mean tPACH was 552 MUm. CONCLUSION: Biomicroscope asymmetry critically
      affects corneal thickness measurement in specular reflection. Induced errors can
      be accounted for and corrected, however. While the correction to the curvature
      radius is clinically relevant, it plays a minor role compared to asymmetry.

PMID- 30197040
TI  - Background and Update for S1602 "A Phase III Randomized Trial to Evaluate the
      Influence of BCG Strain Differences and T Cell Priming with Intradermal BCG
      Before Intravesical Therapy for BCG-naive High-grade Non-muscle-invasive Bladder
      Cancer.
AB  - The S1602 Intergroup trial is a randomized phase III clinical trial that aims to
      test two important hypotheses: (1) priming with intradermal bacillus Calmette
      Guerin (BCG) vaccine prior to standard intravesical BCG improves response to BCG
      in terms of recurrence-free survival and (2) Tokyo-172 BCG strain is non-inferior
      to TICE BCG in terms of time to high-grade recurrence. The study was approved by
      the Cancer Therapy Evaluation Program of the National Cancer Institute and
      activated in spring 2017. Here, we provide a synopsis of the study background,
      design, and update of the clinical trial.

PMID- 30197041
TI  - A Randomized, Double-blind, Phase II Trial of PSA-TRICOM (PROSTVAC) in Patients
      with Localized Prostate Cancer: The Immunotherapy to Prevent Progression on
      Active Surveillance Study.
AB  - The Immunotherapy to Prevent Progression on Active Surveillance Study is the
      first trial of immunotherapy for localized prostate cancer. We randomized active
      surveillance patients to PSA-TRICOM (PROSTVAC) or placebo for 5mo. Final results
      will be available in 2019.

PMID- 30197042
TI  - The Case for Photodynamic Diagnosis-assisted Resection Without Intravesical
      Single-shot Chemotherapy.
AB  - Although there is level 1 evidence for the use of intravesical chemotherapy after
      the transurethral resection of bladder tumour, the decision to apply it needs to
      be individualised. "What benefit will the patient derive from it?"

PMID- 30197043
TI  - Comprehensive Assessment of Indocyanine Green Usage: One Tracer, Multiple
      Urological Applications.
AB  - The intraoperative use of fluorescent tracers and matching cameras can empower
      urologists' ability to recognize critical anatomical and functional features.
      Indocyanine green is the most extensively used near-infrared fluorescent tracer.
      It has been widely applied due to its ability to illuminate vascular and
      lymphatic anatomies. A plurality of fluorescence cameras are available allowing
      the connection of this technology with many surgical approaches, including
      robotic surgery. Although large comparative validation studies are lacking,
      numerous studies support the role of fluorescence guidance in urology.

PMID- 30197045
TI  - Type 1 diabetes: combining technology with personal care.

PMID- 30197044
TI  - The acute transcriptomic response of coral-algae interactions to pH fluctuation.
AB  - Little is known about how the coral host and its endosymbiont interactions change
      when they are exposed to a sudden nonlinear environmental transformation, yet
      this is crucial to coral survival in extreme events. Here, we present a study
      that investigates the transcriptomic response of corals and their endosymbionts
      to an abrupt change in pH (pH 7.60 and 8.35). The transcriptome indicates that
      the endosymbiont demonstrates a synchronized downregulation in carbon acquisition
      and fixation processes and may result in photosynthetic dysfunction in
      endosymbiotic Symbiodinium, suggesting that the mutualistic continuum of coral
      algae interactions is compromised in response to high-CO2 exposure.
      Transcriptomic data also shows that corals are still capable of calcifying in
      response to the low pH but could experience a series of negative effects on their
      energy dynamics, which including protein damage, DNA repair, ion transport,
      cellular apoptosis, calcification acclimation and maintenance of intracellular pH
      homeostasis and stress tolerance to pH swing. This suggests enhanced energy costs
      for coral metabolic adaptation. This study provides a deeper understanding of the
      biological basis related to the symbiotic corals in response to extreme future
      climate change and environmental variability.

PMID- 30197046
TI  - Allergic Contact Dermatitis to Kojic Acid.

PMID- 30197047
TI  - Multiparametric imaging-based differentiation of lymphoma and glioblastoma: using
      T1-perfusion, diffusion, and susceptibility-weighted MRI.
AB  - AIM: To compare the diagnostic performance of T1 perfusion magnetic resonance
      imaging (MRI), diffusion-weighted imaging (DWI), and susceptibility-weighted
      imaging (SWI) for differentiating primary central nervous system lymphoma (PCNSL)
      and glioblastoma (GBM). MATERIALS AND METHODS: This retrospective study comprised
      a cohort of 70 patients with glioblastoma and 30 patients with PCNSL. T1
      perfusion MRI-derived rCBV_corr (leakage corrected relative cerebral blood
      volume), apparent diffusion coefficient (ADC) derived from DWI, and intratumoural
      susceptibility signals intensity (ITSS) measured on SWI were evaluated in these
      100 patients. The Mann-Whitney U-test was used for pairwise comparison between
      groups. The diagnostic performance for differentiating PCNSL from glioblastoma
      was evaluated by using univariate and multivariable logistic regression analyses
      and receiver operating characteristic (ROC) analysis. RESULTS: Minimum ADC,
      maximum rCBVs_corr, kep (back flux exchange rate), and ITSS scores were
      significantly lower in patients with PCNSL than in those with glioblastoma
      (p<0.05). On ROC analysis, ITSS showed the best discrimination ability for
      differentiation of GBM and PCNSL with an area under the ROC curve (AUC) of 0.80.
      rCBV_corr and ADC showed AUCs of 0.68 and 0.63, respectively. Multiparametric
      assessment using ADC, rCBV_corr, kep, and ITSS scores significantly increased the
      diagnostic ability for differentiating PCNSL from GBM as compared to mean ADC,
      mean rCBV_corr, and ITSS alone or a combination of these parameters. The
      multiparametric model could correctly discriminate 84% of tumours with a
      sensitivity and specificity of 90% and 70% with an AUC of 0.92. CONCLUSION:
      Multiparametric MRI evaluation using DWI, T1 perfusion MRI, and SWI enabled
      reliable differentiation of PCNSL and GBM in the majority patients, and these
      results support an integration of advanced MRI techniques for the diagnostic work
      up of patients with these tumours.

PMID- 30197048
TI  - Controversies in Computerized Cognitive Training.
AB  - Computerized cognitive training (CCT) to improve cognitive functioning is of
      enormous interest and has been applied in a broad range of populations with goals
      of improving both cognition and community functioning. Recent reviews presenting
      negative conclusions about CCT efficacy have inconsistent definitions of the
      treatment targets and cognitive improvement. They do not present an accurate
      representation of the typical process of CCT and cognitive remediation (CR),
      especially as delivered in major mental illnesses such as schizophrenia. This
      review provides guidance on the definitions of CCT and CR, the uses of CCT and
      CR, and the definitions and measurements of cognitive and functional gains. The
      review focuses on schizophrenia and healthy aging, with each population receiving
      unique CCT or CR approaches and substantial extant literature with which to
      elucidate fundamental CCT and CR concepts and research findings. It is our
      conclusion that CCT has been shown in most studies to improve cognitive
      performance on untrained tests in healthy older people and in people with
      schizophrenia. Functional gains in schizophrenia appear to be limited to CR
      studies. Clearly defining CCT, CR, and levels of treatment-related gains will be
      critical for understanding the benefits of these widely used treatment programs.

PMID- 30197050
TI  - Let the Diagram Speak: Compass Arcs and Visual Auxiliaries in Printed Diagrams of
      Euclid's Elements.
AB  - The printed Elements in the sixteenth century presented more practical and
      functional diagrams than those of previous manuscripts. Whereas conventional
      diagrams were limited to implementing the description of the text, the new
      diagrams introduced more concise constructions and visual auxiliaries. This
      change toward more practical and functional diagrams reflects the increased
      emphasis on the pedagogical value of the diagram. As is evident from the compass
      arcs upon the diagram, readers of the Elements were invited to draw their own
      diagrams, deviating from tradition and also from the text. Also, the increased
      visual auxiliaries such as correspondence markers, dotted lines, and stereoscopic
      presentations enabled the reader to read diagrams more easily. This backdrop of
      increased engagement with the diagram made it easier for mathematical novices
      (tyrones) to learn the Elements. These tool-based and auxiliaries-laden diagrams
      were more effective for teaching beginners than the earlier, less-functional
      diagrams. This paper explores the function of these new visual vocabularies and
      how they were circulated. This survey comprises a brief history of how diagrams
      began to have their say.

PMID- 30197052
TI  - [Dramatic efficacy of topical ivermectin in idiopathic facial aseptic granuloma].

PMID- 30197051
TI  - Marijuana use by middle-aged and older adults in the United States, 2015-2016.
AB  - BACKGROUND: Marijuana use is increasing among middle-aged and older adults in the
      US, but little is understood of its pattern of use by this population. METHODS:
      We performed a cross-sectional analysis of responses from 17,608 adults aged >=50
      years from the 2015 and 2016 administrations of the National Survey on Drug Use
      and Health. Prevalence of past-year marijuana use was estimated and compared
      between middle-aged adults (age 50-64) and older adults (>=65). Characteristics
      of past-year marijuana users including demographics, substance use, chronic
      disease, and emergency room use, were compared to non-marijuana users and
      stratified by age group. Marijuana use characteristics were also compared between
      middle-aged and older adults. We used multivariable logistic regression to
      determine correlates of past-year marijuana use. RESULTS: Prevalence of past-year
      marijuana use was 9.0% among adults aged 50-64 and 2.9% among adults aged >=65.
      Prevalence of past-year alcohol use disorder (AUD), nicotine dependence, cocaine
      use, and misuse of prescription medications (i.e., opioids, sedatives,
      tranquilizers) were higher among marijuana users compared to non-users. In
      adjusted models, initiation of marijuana use <19 years of age [adjusted odds
      ratio (AOR) = 13.43, 95% confidence interval (CI) 9.60, 18.78)], AUD (AOR = 2.11,
      95% CI 1.51, 2.94), prescription opioid misuse (AOR 2.49, 95% CI 1.61, 3.85),
      nicotine dependence (AOR = 1.90, 95% CI 1.59, 2.26), and cocaine use (AOR 7.43,
      95% CI 4.23, 13.03), were all associated with increased odds of past-year
      marijuana use. CONCLUSION: Marijuana use is becoming more prevalent in this
      population and users are also at high risk for other drug use.

PMID- 30197053
TI  - [Digital necrosis revealing cold agglutinin disease: Treatment with rituximab].
AB  - BACKGROUND: Digital necrosis is rarer than lower limb necrosis and constitutes a
      medical or surgical emergency. Etiological evaluation is required. Cold
      agglutinin disease is a cause of digital necrosis but diagnosis is difficult.
      PATIENTS AND METHODS: Herein we report the case of a 57-year-old man presenting
      recent paroxysmal acrosyndrome of the left hand subsequently complicated by
      digital necrosis following occupational exposure to cold in his work as a
      forklift driver. After etiological evaluation, a diagnosis of primary cold
      agglutinin disease was made. Intravenous rituximab and topical treatment resulted
      in complete healing. DISCUSSION: Cold agglutinin disease is a rare type of auto
      immune hemolytic anemia. Following exposure to cold, paroxysmal cutaneous signs
      are frequent. The disease may be either primary or secondary with B-cell
      lymphoproliferative disorder, auto-immune disease or infection. A thorough workup
      is required. To date, the treatment combining the best positive response rate and
      good safety is rituximab in weekly perfusions over a 1-month period.

PMID- 30197054
TI  - Calculated Risk for Sudden Cardiac Death in Patients with Apical Versus
      Nonobstructive Nonapical Hypertrophic Cardiomyopathy.
AB  - There are limited and conflicting data regarding the prognosis of patients with
      apical hypertrophic cardiomyopathy (HC) and their risk for sudden cardiac death
      (SCD). We used data from a single tertiary center for comparing the clinical
      course and the calculated risk for SCD in patients with nonobstructive apical HC
      (apical HC) versus patients with nonobstructive, nonapical HC (NONA HC). The 5
      year SCD risk was calculated based on the HC risk-SCD tool. A total of 109
      patients were included in the cohort of whom 44 (40%) patients were diagnosed
      with apical HC. The majority of patients were males with a median age at
      diagnosis of 40 years (interquartile range 26, 59 years). Patients with apical HC
      had a significant lower calculated 5-year risk for SCD compared with patients
      with NONA HC (2.65 +/- 2.2% vs 4.00 +/- 3.5%, respectively, p = 0.017), primarily
      due to a lower incidence of familial SCD (20% vs 43% respectively, p = 0.014).
      Only 9% of patients with apical HC had a calculated risk of >6% (implantable
      cardioverter-defibrillator recommended), as compared with 23% of patients with
      NONA HC. During a median follow-up of 1,018 days (interquartile range 546, 1449
      days), apical HC patients tended to develop less malignant ventricular arrhythmia
      episodes compared with NONA HC patients (0% vs 7.7%, respectively, p = 0.060). In
      conclusion, apical HC patients have a lower calculated risk of SCD compared with
      NONA HC patients, mainly due to a lower incidence of family history of SCD. Thus,
      apical HC should be considered a form of HC less prone to SCD.

PMID- 30197055
TI  - Effects of altrenogest on reproductive performance of gilts and sows: A meta
      analysis.
AB  - Altrenogest is a synthetic progestogen that allows for synchronization of the
      time of estrus in swine. Its effect on reproductive performance, however, is
      inconsistent due to conflicting data in the scientific literature. A meta
      analysis of published data, therefore, was performed to determine whether
      altrenogest affects gilt and sow reproductive performance. Altrenogest
      administration to pigs enhanced the number of piglets born alive per litter
      (NBA), total number born per litter (TNB), estrous rate within 10 days after
      treatment (ER10) and pregnancy rate (PR) as well as the farrowing rate (FR) of
      gilts. The NBA and TNB of primiparous sows fed altrenogest were improved although
      FR was less. In multiparous sows, altrenogest treatment did not result in any
      improvement for any of the five analyzed variables. Additionally, 14-day
      treatment regimens for gilts and >8-days for primiparous sows improved
      reproductive performance and extent of estrous synchrony. The effects of
      altrenogest on reproductive performance of swine were parity and treatment
      duration dependent.

PMID- 30197056
TI  - Peri-conceptional nutritional restriction alters transcriptomic profile in the
      peri-implantation pig embryos.
AB  - Restricted nutritional consumption during the peri-conceptional period affects
      the potential for DNA methylation and alters endometrial transcriptomic profile
      during the peri-implantation period. The restricted diet fed to females during
      the peri-conceptional period may affect the transcriptomic profile in peri
      implantation embryos. In the present study, the transcriptome of embryos of
      normal-diet-fed gilts was determined and compared with that in embryos of
      restricted-diet-fed gilts during the peri-implantation period. The restricted
      diet-fed gilts were fed forage, in which the dose of proteins and energy had been
      reduced by 30% compared to the normal diet (Polish Norms of Nutrition). To
      clarify the issue Agilent's Porcine (V2) Two-Color Gene Expression Microarray 4 *
      44 was used. Analysis of the microarray data revealed that the expression of 787
      genes with known biological function were consistently altered (496 up- and 291
      down-regulated) in embryos. The accurately annotated genes were organized into
      five categories and 18 subcategories containing 62 biological pathways. The qPCR
      analysis of ten selected genes [i.e., 5 acid phosphatase, tartrate resistant
      (ACP5), high mobility group box 2 (HMGB2), prostaglandin-endoperoxide synthase 2
      (PTGS2), arachidonate 12-lipoxygenase (ALOX12), adiponectin receptor 2 (ADIPOR2),
      DNA (cytosine-5)-methyltransferase 1 (DNMT1), steroidogenic acute regulatory
      protein (STAR), progesterone receptor membrane component 2 (PGRMC2), progestin
      and adipoQ receptor family member 7 (PAQR7) and serpin family A member 1
      (SERPINA1)] confirmed altered gene expression in embryos of restricted-diet-fed
      gilts. The insight into embryonic transcriptome indicates that female under
      nutrition during the peri-conceptional period may create alterations in the
      pattern of genes expressed in the peri-implantation embryos.

PMID- 30197049
TI  - Association of Whole-Genome and NETRIN1 Signaling Pathway-Derived Polygenic Risk
      Scores for Major Depressive Disorder and White Matter Microstructure in the UK
      Biobank.
AB  - BACKGROUND: Major depressive disorder is a clinically heterogeneous psychiatric
      disorder with a polygenic architecture. Genome-wide association studies have
      identified a number of risk-associated variants across the genome and have
      reported growing evidence of NETRIN1 pathway involvement. Stratifying disease
      risk by genetic variation within the NETRIN1 pathway may provide important routes
      for identification of disease mechanisms by focusing on a specific process,
      excluding heterogeneous risk-associated variation in other pathways. Here, we
      sought to investigate whether major depressive disorder polygenic risk scores
      derived from the NETRIN1 signaling pathway (NETRIN1-PRSs) and the whole genome,
      excluding NETRIN1 pathway genes (genomic-PRSs), were associated with white matter
      microstructure. METHODS: We used two diffusion tensor imaging measures,
      fractional anisotropy (FA) and mean diffusivity (MD), in the most up-to-date UK
      Biobank neuroimaging data release (FA: n = 6401; MD: n = 6390). RESULTS: We found
      significantly lower FA in the superior longitudinal fasciculus (beta = -.035,
      pcorrected = .029) and significantly higher MD in a global measure of thalamic
      radiations (beta = .029, pcorrected = .021), as well as higher MD in the superior
      (beta = .034, pcorrected = .039) and inferior (beta = .029, pcorrected = .043)
      longitudinal fasciculus and in the anterior (beta = .025, pcorrected = .046) and
      superior (beta = .027, pcorrected = .043) thalamic radiation associated with
      NETRIN1-PRS. Genomic-PRS was also associated with lower FA and higher MD in
      several tracts. CONCLUSIONS: Our findings indicate that variation in the NETRIN1
      signaling pathway may confer risk for major depressive disorder through effects
      on a number of white matter tracts.

PMID- 30197057
TI  - The segmental distribution of cervical range of motion: A comparison of ACDF
      versus TDR-C.
AB  - This study was a retrospective radiographic evaluation of patients after cervical
      total disc replacement (TDR-C) or anterior cervical discectomy and fusion (ACDF)
      for one-level cervical disc disease. Our objective was to evaluate (1) total
      cervical (C1-C7) range of motion (ROM) during dynamic imaging, and (2) relative
      contribution to total cervical ROM from operative and adjacent levels.
      Radiographic review of 64 patients who underwent TDR-C (n = 30) or ACDF (n = 34)
      for one-level cervical disc disease. ROM measurements were performed
      independently using a vertebral motion analysis system to evaluate total cervical
      ROM and relative contribution to total ROM from each level (C1-C7) preoperatively
      and at 12-month follow-up. At follow-up, TDR-C patients had significantly greater
      improvement in total cervical ROM (+5.67 degrees , 1.15 mm) than ACDF patients (
      0.96 degrees , 0.12 mm) (P = 0.001). In TDR-C patients, relative contributions to
      total cervical ROM from operative and adjacent caudal and cranial levels were
      statistically equivalent to baseline values. ACDF patients had a significantly
      reduced contribution to total cervical ROM from the operative level (-22.5%, P <
      0.001) and significantly elevated contributions from the adjacent caudal level
      (+16.5%-21.3%, P < 0.001) and from the adjacent first (20.6% vs. 34.6%, P <
      0.001), second (22.9% vs. 30.4%, P < 0.001), and third cranial levels (17.5% vs.
      25.6%, P < 0.001). The cervical spine compensates for loss of ROM at the
      operative level in ACDF patients. However, total cervical ROM increases with TDR
      C and maintains physiologic distribution of ROM throughout the cervical spine at
      12-month follow-up, potentially reducing the risk for adjacent segment breakdown.

PMID- 30197058
TI  - Accuracy of frame-based and frameless systems for deep brain stimulation: A meta
      analysis.
AB  - Deep brain stimulation (DBS) is an effective treatment for movement disorders. It
      relies on the accurate placement of leads within small nuclei in the basal
      ganglia. Traditionally, this has been done with great success using frame-based
      stereotaxy. More recently, frameless systems have been introduced, and several
      studies have investigated whether they can achieve a similar accuracy. The
      objective of this meta-analysis was to assess the difference in targeting
      accuracy between frameless and frame-based systems in deep brain stimulation,
      using prior studies reporting error in all cardinal directions. We recorded the
      mean error and standard deviation, and calculated the composite mean difference
      in error between frame-based and frameless methods using standard difference of
      means. A total of 76 papers were screened, 25 papers were further assessed, and 5
      papers were included in the meta-analysis for a total of 425 DBS electrode
      placements evaluated. Standard difference of means analysis revealed a
      statistically significant benefit to frame-based stereotaxy for the x and y
      coordinates with p = 0.036 and p = 0.0025, respectively. There was no significant
      difference in the z coordinate. However, the mean differences between frame-based
      and frameless stereotaxy was small and the composite mean differences were found
      to be 0.3037 mm, 0.0305 mm, and 0.1630 mm in the x, y and z direction. Our
      analysis shows that frameless systems represent a reasonable alternative to frame
      based methods. Though there was a statistically significant loss of accuracy with
      frameless methods, the size of this effect was very small and of questionable
      clinical significance.

PMID- 30197059
TI  - Chrysophanol attenuates nitrosative/oxidative stress injury in a mouse model of
      focal cerebral ischemia/reperfusion.
AB  - Nitrosative/oxidative stress plays an important role in neuronal death following
      cerebral ischemia/reperfusion (I/R). Chrysophanol (CHR) has been shown to afford
      significant neuroprotection on ischemic stroke, however, whether its mechanism is
      related to attenuating nitrosative/oxidative stress is not clear. In the present
      study, we investigated the effect of CHR on neuronal injury related to nitric
      oxide (NO) production by using mouse middle cerebral artery occlusion (MCAO)
      model. Our results revealed that nitrite plus nitrate (NOx-) and 3-nitrotyrosine
      (3-NT) levels increased in ischemic brain 14 days after reperfusion, and were
      subsequently attenuated by CHR treatment. Moreover, 3-NT is colocalized with NeuN
      and TUNEL, suggesting that neuronal apoptosis following I/R is associated with 3
      NT and CHR suppresses NO-associated neuronal cell death. Accordingly, cleaved
      caspase-3 expression in ischemic brain was decreased by CHR treatment. I/R also
      decreased the activity of total superoxide dismutase (SOD) and manganese
      dependent SOD (MnSOD), whilst increased reactive oxygen species (ROS) production
      significantly. Interestingly, CHR reversed this decrease in total SOD, and MnSOD
      activity, and inhibited ROS generation in the ischemic brain. Taken together, our
      results provide direct evidence suggesting that CHR attenuates
      nitrosative/oxidative stress injury induced by I/R, providing a novel therapeutic
      target in the treatment of acute ischemic stroke.

PMID- 30197060
TI  - Prognostic implications of histological tumor regression (Bohm's score) in
      patients receiving neoadjuvant chemotherapy for high grade serous tubal & ovarian
      carcinoma.
AB  - OBJECTIVE: Primary objective of this study was to determine prognostic
      significance of Bohm's histopathological regression score in patients who
      received neoadjuvant chemotherapy (NACT) for treatment of high grade serous (HGS)
      tubal & ovarian carcinoma. METHODS: This was a retrospective cohort study of
      patients who received NACT between 2010 and 2015. The 3 point histopathological
      regression score of Bohm was used to classify chemotherapy response. Survival
      outcomes between the 3 different subgroups was analysed and compared with
      standard clinico-pathological variables using the Cox proportional hazards model
      and log-rank test. RESULTS: Study cohort comprised 111 patients. Chemotherapy
      response score (CRS) 3 was observed in 47 (42.4%) and CRS 1and CRS 2 in 22
      (19.8%) and 42 (37.8%) women respectively. Women with CRS score of 1 and 2
      combined showed a three-fold increased risk of progression on both univariate and
      multivariate assessment (HR 3.54; C.I 2.19-5.72, p < 0.001). The median overall
      survival for patients with CRS 1 was 34 months, CRS 2 was 30 months and 47 months
      for CRS 3. CRS 1 and 2 combined was the only variable that held significance in
      prediction of reduced overall survival on multivariate assessment (HR 3.26, C.I
      1.91-5.54, p 0.0006). CRS 1 and 2 were also associated with 5.15-fold increased
      risk of relapse within 6 months of completion of chemotherapy (Odds ratio OR
      5.15, C.I 0.07-0.47, p - 0.002). CONCLUSION: CRS is an independent prognosticator
      of survival and reliable predictor of relapse within 6 months in advanced high
      grade serous tubal and ovarian carcinoma patients receiving NACT.

PMID- 30197061
TI  - SPERANZA project: HPV vaccination after treatment for CIN2.

PMID- 30197062
TI  - Tumor-specific outcome of metachronous uterine malignancy after pelvic
      irradiation for cervical cancer.
AB  - OBJECTIVE: To examine survival of women who develop metachronous uterine
      malignancy after definitive pelvic radiotherapy for cervical cancer. METHODS:
      This retrospective observational study examined the Surveillance, Epidemiology,
      End Results Program between 1973 and 2013. Women with cervical cancer who
      received definitive radiotherapy without hysterectomy were examined for the
      diagnosis of metachronous uterine malignancy (n = 5277). Survival was compared
      between metachronous and non-metachronous uterine malignancies according to tumor
      factors. RESULTS: The 10- and 20-year cumulative incidences of metachronous
      uterine malignancy were 0.6% and 1.2%, respectively. When compared to non
      metachronous uterine malignancy, metachronous tumor were more likely to be non
      endometrioid and advanced-stage (both, P < 0.001). As a whole cohort,
      metachronous uterine malignancy was significantly associated with decreased
      overall survival (OS) compared to non-metachronous tumors (hazard ratio [HR]
      4.22, P < 0.001). OS was significantly worse in metachronous compared to non
      metachronous malignancies, although the magnitude of statistical significance was
      greater for endometrioid tumors (HRs for endometrioid versus non-endometrioid:
      6.17 versus 1.92). For grade 1-2 endometrial cancer, metachronous cases had
      significantly decreased OS compared to non-metachronous cases, a larger
      difference than that seen in higher grade tumors (HRs for grade 1-2 versus 3:
      7.79 versus 2.15). Similarly, in early-stage endometrial cancer, metachronous
      cases had significantly decreased OS, with a greater HR compared to advanced
      stage disease (HRs for stage I-II versus III-IV: 5.29 versus 2.29). CONCLUSION:
      Radiotherapy-associated metachronous uterine malignancy after cervical cancer is
      rare but commonly presents with aggressive tumor characteristics. The impact on
      survival is considerably high when metachronous uterine malignancy is
      endometrioid, low-grade, and early-stage.

PMID- 30197063
TI  - Sonochemical synthesis of molybdenum oxide (MoO3) microspheres anchored graphitic
      carbon nitride (g-C3N4) ultrathin sheets for enhanced electrochemical sensing of
      Furazolidone.
AB  - Present strategy introduce the sonochemical synthesis of molybdenum oxide (MoO3)
      microspheres anchored graphitic carbon nitride (g-C3N4) ultrathin sheets as a
      novel electrocatalyst for the detection of Furazolidone (FU). TEM results
      revealed that MoO3 are microspheres with an average size of 2 uM and the g-C3N4
      seems like ultrathin sheets. Owing to their peculiar morphological structure, g
      C3N4/MoO3 composite modified electrode provided an enriched electroactive surface
      area (0.3788 cm2) and higher heterogeneous electron transfer kinetics (K degrees
      eff = 4.91*10-2 cm s-1) than the other controlled electrodes. It is obviously
      observed from the voltammetric studies that the proposed sensor based on g
      C3N4/MoO3 composite can significantly improve the electrocatalytic efficiency
      towards the sensing of FU. Due to the excellent synergic effect of g-C3N4/MoO3
      composite, can detect the ultra-level FU with a limit of detection of 1.4 nM and
      a broad dynamic range of 0.01-228 uM, which surpassed the many previously
      reported FU sensors. Hence, the proposed sensor was successfully applied to
      sensing the FU in human blood serum, urine and pharmaceutical samples, gained an
      agreeable recoveries.

PMID- 30197064
TI  - Oxygen-rich bismuth oxychloride Bi12O17Cl2 materials: construction,
      characterization, and sonocatalytic degradation performance.
AB  - In this study, a series of oxygen-rich bismuth oxychloride Bi12O17Cl2 samples
      were prepared at different calcination temperatures and characterized by X-ray
      diffraction patterns, UV-Vis diffuse reflectance spectra, scanning electron
      microscope, X-ray energy dispersion spectroscope, X-ray photoelectron
      spectroscopy, and photoluminescence spectroscopy. The calcination temperature
      greatly affected microstructures and band structures of as-prepared samples,
      further influencing sonocatalytic degradation efficiencies over dye Rhodamine B.
      Some dependant factors such as ultrasonic power, catalyst dosage, pH value,
      initial concentration of Rhodamine B, and reaction temperature were
      systematically investigated and the robust sample Bi12O17Cl2-550 with a favorable
      microstructure and band structure provided the best sonocatalytic removal
      efficiency around 90% at the optimal condition. Based upon reactive species
      entrapping and hydroxyl radical detection experiments, a primary sonocatalysis
      mechanism was eventually speculated.

PMID- 30197065
TI  - Nipple-sparing mastectomy with different approaches: surgical incisions,
      complications, and cosmetic results. Preliminary results of 100 consecutive
      patients at a single center.
AB  - Nipple- and areola-sparing mastectomy is a novel surgical approach that preserves
      the nipple-areolar complex. Patients with moderate and/or severe breast ptosis
      are usually not eligible for this surgical approach. In this study, we aimed to
      demonstrate the feasibility of nonconventional surgical approaches for nipple
      sparing mastectomy. One hundred consecutive patients diagnosed with primary
      breast cancer (BC) were enrolled in this study. Clinical and pathological data
      such as body mass index, smoking status, breast ptosis, complications, and
      aesthetic satisfaction (Breast-Q test) were collected. According to different
      types of breast ptosis, surgical procedures were classified as (a) hemi
      periareolar, (b) round block, (c) vertical pattern, and (d) wise pattern skin
      incisions. We performed statistical analysis to assess the correlation with
      complications, degree of ptosis, and breast-Q scores. Among the 117 surgical
      procedures performed in 100 patients with BC, no significant associations are
      verified considering clinical and pathological data, complications, pre- and
      postsurgery satisfactions, and other parameters. Different surgical approaches
      represent the evolution of "classic" nipple-sparing mastectomy, thus meeting the
      cosmetic and oncological results. These procedures are safe and also indicated in
      cases conventionally considered as not eligible for nipple-areola preservation.

PMID- 30197066
TI  - Risk factors for developing capsular contracture in women after breast implant
      surgery: A systematic review of the literature.

PMID- 30197067
TI  - Eosinophils: Friends or Foes?
AB  - The roles eosinophils are recognized to play in health and disease continue to
      evolve. Formerly, eosinophils were believed to fill a primary role in host
      defense against helminths, an intermediary one in the propagation of allergic
      conditions, and a pathologic one in clinical conditions characterized by systemic
      eosinophilia and eosinophilic infiltration of target organs. Eosinophils are
      increasingly understood to be positioned centrally within mammalian immune and
      inflammatory networks, possessing receptors for an array of inflammatory
      mediators and capable of producing numerous proinflammatory and homeostatic
      mediators. The concept has emerged that eosinophils play a major role in the
      modulation of allergic inflammation and in the repair of damaged tissues in
      diseases characterized by eosinophilic infiltration. Possible new emerging roles
      for eosinophils include neoplasm surveillance, tissue remodeling during puberty
      and pregnancy, and the restructuring of adipose tissue. The eosinophil
      granulocyte line appeared hundreds of millions of years ago during the
      evolutionary process and continues to be retained by all vertebrate species. This
      is strong evidence that although all the beneficial roles of eosinophils have yet
      to emerge, eosinophils, on balance, must be considered friends and not foes.

PMID- 30197069
TI  - Eosinophilic Granulomatosis with Polyangiitis: Clinical Pathology Conference and
      Review.
AB  - Eosinophilic granulomatosis with polyangiitis (EGPA) (formerly Churg-Strauss
      syndrome) is a small vessel vasculitis associated with asthma and eosinophilia.
      Despite its rarity, continuous gains are being made in understanding the disease
      with knowledge advancements regarding its epidemiology, heterogeneous clinical
      manifestations, management, and outcomes. Large knowledge gaps remain, however,
      particularly surrounding pathophysiologic and diagnostic uncertainties. There is
      still an incomplete understanding of the interplay between the eosinophilic and
      vasculitic processes that are features of disease pathogenesis. EGPA is also a
      conceptually difficult disorder given its dual categorization with
      hypereosinophilic syndromes and systemic vasculitides and the absence of a
      biomarker that can reliably distinguish between the two. In addition, recent
      evidence points to distinct, but partly overlapping, disease phenotypes, yet
      there is insufficient understanding to inform phenotype-tailored therapies. EGPA
      also remains a diagnostic challenge in part because asthma may be the primary or
      predominant manifestation for years, and the chronic corticosteroid requirement
      may mask other disease features. Efforts are ongoing to better elucidate
      pathophysiologic mechanisms, resolve classification issues, better characterize
      disease manifestations, and further clarify disease subcategorization, all of
      which will translate into better diagnosis and treatment with the possibility of
      specifically adapted therapies.

PMID- 30197070
TI  - Eosinophils and the Scope of Practice in Allergy/Immunology.

PMID- 30197068
TI  - Consultation for Elevated Blood Eosinophils: Clinical Presentations, High Value
      Diagnostic Tests, and Treatment Options.
AB  - The workup of a patient found to have eosinophilia should follow a thorough path
      with a detailed history and physical examination aimed at eliciting eosinophilic
      organ involvement, followed by histological confirmation whenever possible. The
      differential diagnosis of hypereosinophilia is extensive, but a rational approach
      beyond the history and physical examination including serologic, blood, and bone
      marrow cell analyses, genetic testing, and radiologic imaging can distinguish
      many of the causes. Often input from specialists (eg, hematology, dermatology,
      pulmonary, gastroenterology, and neurology) can help narrow down the
      possibilities and eventually result in a specific diagnosis. An accurate
      diagnosis is key to choosing the optimal treatment for a particular condition,
      and this is certainly true for eosinophilic disorders. Myeloid neoplasms that
      present with eosinophilia, for example, may respond to medicines that the
      allergist may be less accustomed to using, such as immunosuppressive agents and
      kinase inhibitors. Similarly, newly approved biologics that target IL-5 and
      eosinophils may provide new options for management. What follows is a case-based
      approach that helps to underscore key features of diagnosis, management, and
      follow-up when faced with a patient with a potential eosinophil-related disorder.

PMID- 30197071
TI  - How Important Is Adherence to Inhaled Medications Before Starting a Biologic
      Therapy for Asthma?

PMID- 30197072
TI  - Hypersensitivity to Neuromuscular Blocking Agents: Can Skin Tests Give the Green
      Light for Re-Exposure?

PMID- 30197073
TI  - Eosinophilic Esophagitis.

PMID- 30197074
TI  - Treating chronic spontaneous urticaria in children.

PMID- 30197075
TI  - Reply.

PMID- 30197076
TI  - Indoor environmental interventions for furry pet allergens: How to decrease the
      degree of passive transport.

PMID- 30197077
TI  - Possible contribution of decreased phytoprostanes to diet-induced improvements in
      aspirin exacerbated respiratory disease.

PMID- 30197078
TI  - Correction.

PMID- 30197080
TI  - Correction.

PMID- 30197079
TI  - Correction.

PMID- 30197081
TI  - Mutations in Disordered Regions Can Cause Disease by Creating Dileucine Motifs.
AB  - Many disease-causing missense mutations affect intrinsically disordered regions
      (IDRs) of proteins, but the molecular mechanism of their pathogenicity is
      enigmatic. Here, we employ a peptide-based proteomic screen to investigate the
      impact of mutations in IDRs on protein-protein interactions. We find that
      mutations in disordered cytosolic regions of three transmembrane proteins (GLUT1,
      ITPR1, and CACNA1H) lead to an increased clathrin binding. All three mutations
      create dileucine motifs known to mediate clathrin-dependent trafficking. Follow
      up experiments on GLUT1 (SLC2A1), the glucose transporter causative of GLUT1
      deficiency syndrome, revealed that the mutated protein mislocalizes to
      intracellular compartments. Mutant GLUT1 interacts with adaptor proteins (APs) in
      vitro, and knocking down AP-2 reverts the cellular mislocalization and restores
      glucose transport. A systematic analysis of other known disease-causing variants
      revealed a significant and specific overrepresentation of gained dileucine motifs
      in structurally disordered cytosolic domains of transmembrane proteins. Thus,
      several mutations in disordered regions appear to cause "dileucineopathies."

PMID- 30197083
TI  - Neural Entrainment Determines the Words We Hear.
AB  - Low-frequency neural entrainment to rhythmic input has been hypothesized as a
      canonical mechanism that shapes sensory perception in time. Neural entrainment is
      deemed particularly relevant for speech analysis, as it would contribute to the
      extraction of discrete linguistic elements from continuous acoustic signals.
      However, its causal influence in speech perception has been difficult to
      establish. Here, we provide evidence that oscillations build temporal predictions
      about the duration of speech tokens that affect perception. Using
      magnetoencephalography (MEG), we studied neural dynamics during listening to
      sentences that changed in speech rate. We observed neural entrainment to
      preceding speech rhythms persisting for several cycles after the change in rate.
      The sustained entrainment was associated with changes in the perceived duration
      of the last word's vowel, resulting in the perception of words with different
      meanings. These findings support oscillatory models of speech processing,
      suggesting that neural oscillations actively shape speech perception.

PMID- 30197084
TI  - Rapid Antagonistic Coevolution in an Emerging Pathogen and Its Vertebrate Host.
AB  - Host-pathogen coevolution is assumed to play a key role in eco-evolutionary
      processes, including epidemiological dynamics and the evolution of sexual
      reproduction [1-4]. Despite this, direct evidence for host-pathogen coevolution
      is exceptional [5-7], particularly in vertebrate hosts. Indeed, although
      vertebrate hosts have been shown to evolve in response to pathogens or vice versa
      [8-12], there is little evidence for the necessary reciprocal changes in the
      success of both antagonists over time [13]. Here, we generate a time-shift
      experiment to demonstrate adaptive, reciprocal changes in North American house
      finches (Haemorhous mexicanus) and their emerging bacterial pathogen, Mycoplasma
      gallisepticum [14-16]. Our experimental design is made possible by the existence
      of disease-exposed and unexposed finch populations, which were known to exhibit
      equivalent responses to experimental inoculation until the recent spread of
      genetic resistance in the former [14, 17]. Whereas inoculations with pathogen
      isolates from epidemic outbreak caused comparable sub-lethal eye swelling in
      hosts from exposed (hereafter adapted) and unexposed (hereafter ancestral)
      populations, inoculations with isolates sampled after the spread of resistance
      were threefold more likely to cause lethal symptoms in hosts from ancestral
      populations. Similarly, the probability that pathogens successfully established
      an infection in the primary host and, before inducing death, transmitted to an
      uninfected sentinel was highest when recent isolates were inoculated in hosts
      from ancestral populations and lowest when early isolates were inoculated in
      hosts from adapted populations. Our results demonstrate antagonistic host
      pathogen coevolution, with hosts and pathogens displaying increased resistance
      and virulence in response to each other over time.

PMID- 30197082
TI  - Extracellular Matrix Remodeling Regulates Glucose Metabolism through TXNIP
      Destabilization.
AB  - The metabolic state of a cell is influenced by cell-extrinsic factors, including
      nutrient availability and growth factor signaling. Here, we present extracellular
      matrix (ECM) remodeling as another fundamental node of cell-extrinsic metabolic
      regulation. Unbiased analysis of glycolytic drivers identified the hyaluronan
      mediated motility receptor as being among the most highly correlated with
      glycolysis in cancer. Confirming a mechanistic link between the ECM component
      hyaluronan and metabolism, treatment of cells and xenografts with hyaluronidase
      triggers a robust increase in glycolysis. This is largely achieved through rapid
      receptor tyrosine kinase-mediated induction of the mRNA decay factor ZFP36, which
      targets TXNIP transcripts for degradation. Because TXNIP promotes internalization
      of the glucose transporter GLUT1, its acute decline enriches GLUT1 at the plasma
      membrane. Functionally, induction of glycolysis by hyaluronidase is required for
      concomitant acceleration of cell migration. This interconnection between ECM
      remodeling and metabolism is exhibited in dynamic tissue states, including
      tumorigenesis and embryogenesis.

PMID- 30197085
TI  - A Switch in Microtubule Orientation during C. elegans Meiosis.
AB  - In oocytes of many organisms, meiotic spindles form in the absence of centrosomes
      [1-5]. Such female meiotic spindles have a pointed appearance in metaphase with
      microtubules focused at acentrosomal spindle poles. At anaphase, the microtubules
      of acentrosomal spindles then transition to an inter-chromosomal array, while the
      spindle poles disappear. This transition is currently not understood. Previous
      studies have focused on this inter-chromosomal microtubule array and proposed a
      pushing model to drive chromosome segregation [6, 7]. This model includes an end
      on orientation of microtubules with chromosomes. Alternatively, chromosomes were
      thought to associate along bundles of microtubules [8, 9]. Starting with
      metaphase, this second model proposed a pure lateral chromosome-to-microtubule
      association up to the final meiotic stages of anaphase. Here, we applied large
      scale electron tomography [10] of staged C. elegans oocytes in meiosis to analyze
      the orientation of microtubules in respect to chromosomes. We show that
      microtubules at metaphase I are primarily oriented laterally to the chromosomes
      and that microtubules switch to an end-on orientation during progression through
      anaphase. We further show that this switch in microtubule orientation involves a
      kinesin-13 microtubule depolymerase, KLP-7, which removes laterally associated
      microtubules around chromosomes. From this, we conclude that both lateral and end
      on modes of microtubule-to-chromosome orientations are successively used in C.
      elegans oocytes to segregate meiotic chromosomes.

PMID- 30197086
TI  - Direct Electrophysiological Evidence for Prefrontal Control of Hippocampal
      Processing during Voluntary Forgetting.
AB  - Forgetting does not necessarily reflect failure to encode information but can, to
      some extent, also be voluntarily controlled. Previous studies have suggested that
      voluntary forgetting relies on active inhibition of encoding processes in the
      hippocampus by the dorsolateral prefrontal cortex (DLPFC) [1-4]. During
      attentional and sensorimotor processing, enhanced DLPFC theta power alongside
      increased alpha/beta oscillations are a neural signature of an inhibitory top
      down mechanism, with theta oscillations reflecting prefrontal control and
      alpha/beta oscillations occurring in areas targeted by inhibition [5-12]. Here,
      we used intracranial EEG recordings in presurgical epilepsy patients implanted in
      DLPFC (n = 13) and hippocampus (n = 15) during an item-method directed forgetting
      paradigm. We found that voluntary forgetting is associated with increased neural
      oscillations in the low theta band (3-5 Hz) in DLPFC and in a broad
      theta/alpha/beta (6-18 Hz) frequency range in hippocampus. Combining time-lagged
      correlation analysis, phase synchronization, and Granger causality in 6 patients
      with electrodes in both DLPFC and hippocampus, we obtained converging evidence
      for a top-down control of hippocampal activity by the DLPFC. Together, our
      results provide strong support for a model in which voluntary forgetting relies
      on enhanced inhibition of the hippocampus by the DLPFC.

PMID- 30197087
TI  - Cortico-hippocampal Schemas Enable NMDAR-Independent Fear Conditioning in Rats.
AB  - The neurobiology of memory formation has been studied primarily in experimentally
      naive animals, but the majority of learning unfolds on a background of prior
      experience. Considerable evidence now indicates that the brain processes initial
      and subsequent learning differently. In rodents, a first instance of contextual
      fear conditioning requires NMDA receptor (NMDAR) activation in the dorsal
      hippocampus, but subsequent conditioning to another context does not. This shift
      may result from a change in molecular plasticity mechanisms or in the information
      required to learn the second task. To clarify how related events are encoded, it
      is critical to identify which aspect of a first task engages NMDAR-independent
      learning and the brain regions that maintain this state. Here, we show in rats
      that the requirement for NMDARs in hippocampus depends neither on prior exposure
      to context nor footshock alone but rather on the procedural similarity between
      two conditioning tasks. Importantly, NMDAR-independent learning requires the
      memory of the first task to remain hippocampus dependent. Furthermore, disrupting
      memory maintenance in the anterior cingulate cortex after the first task also
      reinstates NMDAR dependency. These results reveal cortico-hippocampal
      interactions supporting experience-dependent learning.

PMID- 30197088
TI  - The Genetic Basis of Adaptation following Plastic Changes in Coloration in a
      Novel Environment.
AB  - Phenotypic plasticity has been hypothesized to precede and facilitate adaptation
      to novel environments [1-8], but examples of plasticity preceding adaptation in
      wild populations are rare (but see [9, 10]). We studied a population of side
      blotched lizards, Uta stansburiana, living on a lava flow that formed 22,500
      years ago [11] to understand the origin of their novel melanic phenotype that
      makes them cryptic on the black lava. We found that lizards living on and off of
      the lava flow exhibited phenotypic plasticity in coloration but also appeared to
      have heritable differences in pigmentation. We sequenced the exomes of 104
      individuals and identified two known regulators of melanin production, PREP and
      PRKAR1A, which had markedly increased levels of divergence between lizards living
      on and off the lava flow. The derived variants in PREP and PRKAR1A were only
      found in the lava population and were associated with increased pigmentation
      levels in an experimental cohort of hatchling lizards. Simulations suggest that
      the derived variants in the PREP and PRKAR1A genes arose recently and were under
      strong positive selection in the lava population. Overall, our results suggest
      that ancestral plasticity for coloration facilitated initial survival in the lava
      environment and was followed by genetic changes that modified the phenotype in
      the direction of the induced plastic response, possibly through de novo
      mutations. These observations provide a detailed example supporting the
      hypothesis that plasticity aids in the initial colonization of a novel habitat,
      with natural selection subsequently refining the phenotype with genetic
      adaptations to the new environment. VIDEO ABSTRACT.

PMID- 30197090
TI  - Exaptation as a Mechanism for Functional Reinforcement of an Animal Pheromone
      System.
AB  - Animal sex pheromone systems often exist as multicomponent signals [1-11] to
      which chemical cues have been added over evolutionary time. Little is known on
      why and how additional molecules become recruited and conserved in an already
      functional pheromone system. Here, we investigated the evolutionary trajectory of
      a series of 15 kDa proteins-termed persuasins-that were co-opted more recently
      alongside the ancient sodefrin precursor-like factor (SPF) courtship pheromone
      system in salamanders [9, 12]. Expression, genomic, and molecular phylogenetic
      analyses show that persuasins originated from a gene that is expressed as a multi
      domain protein in internal organs where it has no pheromone function but
      underwent gene duplication and neofunctionalization. The subsequent evolution
      combined domain loss and the introduction of a proteolytic cleavage site in the
      duplicated gene to give rise to two-domain cysteine rich proteins with structural
      properties similar to SPF pheromones [12]. An expression shift to the pheromone
      producing glands, where expression of persuasins was immediately spatiotemporally
      synchronized with the already available pheromone system, completed the birth of
      a new pheromone. Electrostatic forces between members of both protein families
      likely enhance co-localization and simultaneous activation of different female
      olfactory neurons, explaining why persuasins immediately had a selective
      advantage. In line with this, behavioral assays show that persuasins increase
      female receptivity on their own but also exert a cumulative or synergistic effect
      in combination with SPF, clearly reinforcing the pheromone system as a whole. Our
      study reveals molecular remodeling of an existing protein architecture as an
      evolutionary mechanism for functional reinforcement of animal pheromone systems.

PMID- 30197091
TI  - Optimal treatment for African-Americans with intractable mesial temporal lobe
      epilepsy remains anterior temporal lobectomy.

PMID- 30197089
TI  - IRTKS (BAIAP2L1) Elongates Epithelial Microvilli Using EPS8-Dependent and
      Independent Mechanisms.
AB  - Transporting epithelial cells like those that line the gut build large arrays of
      actin-supported protrusions called microvilli, which extend from the apical
      surface into luminal spaces to increase functional surface area. Although
      critical for maintaining physiological homeostasis, mechanisms controlling the
      formation of microvilli remain poorly understood. Here, we report that the
      inverse-bin-amphiphysin-Rvs (I-BAR)-domain-containing protein insulin receptor
      tyrosine kinase substrate (IRTKS) (also known as BAIAP2L1) promotes the growth of
      epithelial microvilli. Super-resolution microscopy and live imaging of
      differentiating epithelial cells revealed that IRTKS localizes to the distal tips
      of actively growing microvilli via a mechanism that requires its N-terminal I-BAR
      domain. At microvillar tips, IRTKS promotes elongation through a mechanism
      involving its C-terminal actin-binding WH2 domain. IRTKS can also drive
      microvillar elongation using its SH3 domain to recruit the bundling protein EPS8
      to microvillar tips. These results provide new insight on mechanisms that control
      microvillar growth during the differentiation of transporting epithelial cells
      and help explain why IRTKS is targeted by enteric pathogens that disrupt
      microvillar structure during infection of the intestinal epithelium.

PMID- 30197092
TI  - Impact of carbapenem versus non-carbapenem treatment on the rates of
      superinfection: A meta-analysis of randomized controlled trials.
AB  - Imipenem and meropenem are the recommended antipseudomonal carbapenems for
      nosocomial pneumonia per clinical practice guidelines. However, these agents have
      a relatively broader spectrum of activity than other antibiotics and need to be
      reserved. Carbapenems might cause higher rate of superinfection. The aim of this
      study was to compare the rate of superinfection between patients who received
      imipenem or meropenem versus those who received non-carbapenem treatment. PubMed,
      EMBASE, Cochrane Library databases and two trial registries were searched for
      relevant randomized controlled trials of hospitalized adults with pneumonia
      through February 24, 2017 without date or language restrictions. Risk ratios
      (RRs) with 95% confidence intervals (CIs) were estimated using random-effects
      models. The primary outcome was based on the intention-to-treat analysis while
      clinically evaluable patients were analyzed as secondary outcome. Eight RCTs were
      included in this meta-analysis. A statistically higher risk of superinfection
      with low heterogeneity (RR = 1.690, 95% CI 1.247-2.291, p = 0.001, I2 = 0%) was
      associated with the two carbapenems compared to non-carbapenems. However, in
      comparison with non-carbapenems, superinfection with imipenem was significantly
      higher (RR = 1.694, 95% CI 1.234-2.325, p = 0.001, I2 = 0%), while it was non
      significant with meropenem (RR = 1.647, 95% CI 0.552-4.919, p = 0.371, I2 = 0%).
      Superinfection was statistically higher in both double-blind and open-label
      studies and when carbapenems were compared to other antipseudomonal beta-lactams.
      This meta-analysis identified significantly higher superinfection with imipenem
      compared to non-carbapenems. The findings confirm the theory of higher
      superinfections with broader spectrum agents and provide additional support for
      reserving carbapenems for the treatment of infections caused by multidrug
      resistant organisms.

PMID- 30197093
TI  - Evaluation of three automated Treponema pallidum antibody assays for syphilis
      screening.
AB  - The accuracy of the test is critical for the syphilis serology diagnosis. This
      study aims to evaluate the values of the Elecsys syphilis assay, the Architect
      syphilis assay, and the Mindray syphilis assay, as syphilis screening tests for
      pregnant women and patients with syphilis or other diseases. A reverse algorithm
      was used for the syphilis serology diagnosis. Serum samples (n = 584) were tested
      with three automated screening assays. All reactive sera by one, two, or three
      screening assays were further analyzed with the tolulized red unheated serum test
      (TRUST). Inconsistent results were confirmed by the Treponema pallidum particle
      agglutination assay (TPPA). The final patient diagnosis was made according to the
      results of syphilis serology, clinical evidence, and past medical history. The
      sensitivity, specificity, accuracy, and kappa value of each assay were as
      follows: for the Elecsys syphilis assay, 100.0%, 98.5%, 98.6%, and 0.927,
      respectively; for the Architect syphilis assay: 100.0%, 94.5%, 95.0%, and 0.770;
      and for the Mindray syphilis assay: 100.0%, 97.0%, 97.3%, and 0.862. The McNemar
      test showed that there were significant differences in the performance between
      the Elecsys syphilis assay and the Architect syphilis assay (P < 0.001), and
      between the Mindray syphilis assay and the Architect syphilis assay (P = 0.001).
      Our study demonstrated that three automated Treponema pallidum antibody assays
      generally showed high sensitivities and specificities, and so, they are suitable
      for use in screening for syphilis. The performances of the Elecsys syphilis assay
      and the Mindray syphilis assay are superior to Architect syphilis assay.

PMID- 30197094
TI  - Electromyographic analysis of infraspinatus and scapular muscles during external
      shoulder rotation with different weight loads and positions.
AB  - BACKGROUND: Strengthening the infraspinatus is important in shoulder
      rehabilitation. Changes in infraspinatus activity with changing load and position
      have not been quantified. We sought to determine the most appropriate load and
      posture for early infraspinatus strengthening by assessing for changes in
      electromyographic activity in the healthy infraspinatus and other shoulder girdle
      muscles during isometric external rotational exercise under different loads with
      the shoulder adducted in the supine and seated positions. METHODS: Sixteen
      healthy adults (30 shoulders) performed isometric shoulder external rotation in
      the sitting and supine positions, starting with the shoulder and forearm in
      neutral position and the elbow flexed 90 degrees . Loads (0.5 kg, 1 kg, and 2 kg)
      were applied at rest. We assessed the infraspinatus, upper trapezius, posterior
      deltoid, and biceps brachii. For analysis, we used the mean percentage of maximum
      voluntary muscle contraction (%MVC) value measured during each isometric
      contraction divided by the maximum voluntary muscle contraction (MVC) of each
      muscle. RESULTS: In the infraspinatus and posterior deltoid, significant
      interaction was observed between body position and load. Compared to the sitting
      position, an increase in activity in the supine position was attenuated as load
      increased, especially at 2 kg. The supine values of the upper trapezius and
      biceps brachii were always significantly lower than those in the sitting position
      regardless of load. CONCLUSION: The activity of the infraspinatus can be
      increased gradually during rehabilitation by beginning in the supine position,
      which assures low activity of the upper trapezius and biceps brachii. Exercise
      with the shoulder adducted in the supine position can strengthen the
      infraspinatus gradually and avoid compensatory mobility. LEVEL OF EVIDENCE: Level
      3.

PMID- 30197096
TI  - The Challenges of Using MRI During Radiotherapy.
AB  - In this article we aim to introduce the main considerations in integrating
      magnetic resonance imaging (MRI) into the radiotherapy workflow. We will cover
      the use of MRI for improved delineation, considerations regarding MRI-only
      workflows, and the potential of functional imaging techniques. The challenges of
      implementing each of these will be discussed to ensure safe usage in
      radiotherapy.

PMID- 30197095
TI  - Magnetic Resonance Image-Guided Radiotherapy (MRIgRT): A 4.5-Year Clinical
      Experience.
AB  - AIMS: Magnetic resonance image-guided radiotherapy (MRIgRT) has been clinically
      implemented since 2014. This technology offers improved soft-tissue
      visualisation, daily imaging, and intra-fraction real-time imaging without added
      radiation exposure, and the opportunity for adaptive radiotherapy (ART) to adjust
      for anatomical changes. Here we share the longest single-institution experience
      with MRIgRT, focusing on trends and changes in use over the past 4.5 years.
      MATERIALS AND METHODS: We analysed clinical information, including patient
      demographics, treatment dates, disease sites, dose/fractionation, and clinical
      trial enrolment for all patients treated at our institution using MRIgRT on a
      commercially available, integrated 0.35 T MRI, tri-cobalt-60 device from 2014 to
      2018. For each patient, factors including disease site, clinical rationale for
      MRIgRT use, use of ART, and proportion of fractions adapted were summated and
      compared between individual years of use (2014-2018) to identify shifts in
      institutional practice patterns. RESULTS: Six hundred and forty-two patients were
      treated with 666 unique treatment courses using MRIgRT at our institution between
      2014 and 2018. Breast cancer was the most common disease, with use of cine MRI
      gating being a particularly important indication, followed by abdominal sites,
      where the need for cine gating and use of ART drove MRIgRT use. One hundred and
      ninety patients were treated using ART in 1550 fractions, 67.6% (1050) of which
      were adapted. ART was primarily used in cancers of the abdomen. Over time, breast
      and gastrointestinal cancers became increasingly dominant for MRIgRT use,
      hypofractionated treatment courses became more popular, and gastrointestinal
      cancers became the principal focus of ART. DISCUSSION: MRIgRT is widely
      applicable within the field of radiation oncology and new clinical uses continue
      to emerge. At our institution to date, applications such as ART for
      gastrointestinal cancers and accelerated partial breast irradiation (APBI) for
      breast cancer have become dominant indications, although this is likely to
      continue to evolve.

PMID- 30197097
TI  - Beam parameters optimization and characterization for a TUrning LInac for
      Protontherapy.
AB  - TULIP (TUrning LInac for Protontherapy) is a novel compact accelerator system for
      protontherapy mounted on a rotating gantry (Amaldi et al., 2013, 2010, 2009). Its
      high-energy Linac has the unique property of being able to modulate the beam
      energy from one pulse to the next, in only a couple of milliseconds. The main
      purpose of this study is to optimize the properties of the beam exiting the Linac
      to make them compatible to medical therapy and to characterize their medical
      physics properties for later implementation in a Treatment Planning System. For
      this purpose, multi-particle tracking and Monte Carlo (MC) simulations are used
      to follow the particles through their path up to the treatment isocenter,
      following the so-called phase-space method. The data compiled includes particle
      fluences in air and depth-dose curves and provides the basis for a specific model
      of the TULIP beam.

PMID- 30197098
TI  - Clinical Development of Darolutamide: A Novel Androgen Receptor Antagonist for
      the Treatment of Prostate Cancer.
AB  - Prostate cancer (PC) is the second most common cancer in men and is the fifth
      leading cause of cancer-related deaths among men. Androgen receptor (AR)
      signaling plays a key role in PC tumor growth and progression, with androgens
      stimulating PC proliferation and survival. Castration-resistant PC (CRPC) is
      characterized by increasing levels of prostate-specific antigen or radiographic
      progression despite androgen-deprivation therapy (ADT). In most patients,
      castration resistance results from aberrations in AR or the AR signaling pathway.
      Up to one-third of patients with localized high-risk PC will have disease
      progression on local therapy and develop CRPC. This review summarizes the key
      clinical data, including ongoing trials, for hormonal therapies in CRPC and
      provides an overview of the clinical development of darolutamide, a novel,
      nonsteroidal AR antagonist currently in phase III development for the treatment
      of nonmetastatic CRPC and metastatic hormone-sensitive PC. In phase I/II trials,
      darolutamide has demonstrated a favorable safety profile, antitumor activity, and
      significant decreases in prostate-specific antigen in patients with metastatic
      CRPC. In the phase III ARAMIS (NCT02200614; A Multinational, Randomized, Double
      Blind, Placebo-Controlled, Phase III Efficacy and Safety Study of Darolutamide
      [ODM-201] in Men With High-Risk Non-metastatic Castration-Resistant Prostate
      Cancer) study, metastasis-free survival is being evaluated in men with
      nonmetastatic CRPC who will receive ADT in combination with darolutamide or
      placebo. The ARASENS (NCT02799602; A Randomized, Double-Blind, Placebo Controlled
      Phase III Study of Darolutamide [ODM-201] Versus Placebo in Addition to Standard
      Androgen Deprivation Therapy and Docetaxel in Patients With Metastatic Hormone
      Sensitive Prostate Cancer) study is a placebo-controlled trial assessing whether
      the addition of darolutamide to ADT and docetaxel significantly prolongs overall
      survival in men with metastatic hormone-sensitive PC.

PMID- 30197099
TI  - The prostacyclin analogue Iloprost as an early predictor of successful
      revascularization in diabetic patients affected by critical limb ischemia and
      foot ulcers.
AB  - PURPOSE: The aim of this study is to evaluate the role of Iloprost as an early
      predictor of successful revascularization in patients affected by ischemic
      diabetic foot ulcers (DFUs). METHODS: Consecutive patients with ischemic DFUs
      with persistent low TcPO2 (<30mmHg) one day after a technical successful
      Percutaneous Transluminal Angioplasty (PTA) have been included. All patients
      underwent Iloprost infusion and TcPO2 has been recorded at days 3, 14 and 30.
      According to the TcPO2 reported at day 3, patients were divided into two groups:
      group A (patients with TcPO2 >=30mmHg) and group B (patients with TcPO2 <30mmHg).
      Baseline TcPO2 values at days 3, 14 and 30 after Iloprost infusion and needing of
      re-intervention (re-PTA) have been evaluated. RESULTS: Twenty-five patients have
      been included, 12/25 (48%) in Group A and 13/25 (52%) in Group B. There were no
      significant differences at the baseline and one day after PTA between the two
      groups while TcPO2 values recorded in Group A at days 3, 14 and 30 after Iloprost
      infusion were significant higher in comparison to the Group B (chi = 0.005). The
      rate of re-PTA were respectively 33,3% (Group A) and 53,8% (Group B) (p = 0.03).
      CONCLUSIONS: Iloprost may be an early predictor of successful revascularization
      in patients affected by critical limb ischemia (CLI) and DFUs.

PMID- 30197100
TI  - Do we need a guide for left main stenting?

PMID- 30197101
TI  - All-cause mortality among people with HIV released from an integrated system of
      jails and prisons in Connecticut, USA, 2007-14: a retrospective observational
      cohort study.
AB  - BACKGROUND: People transitioning from prisons or jails have high mortality, but
      data are scarce for people with HIV and no studies have integrated data from both
      criminal justice and community settings. We aimed to assess all-cause mortality
      in people with HIV released from an integrated system of prisons and jails in
      Connecticut, USA. METHODS: We linked pharmacy, custodial, death, case management,
      and HIV surveillance data from Connecticut Departments of Correction and Public
      Health to create a retrospective cohort of all adults with HIV released from
      jails and prisons in Connecticut between 2007 and 2014. We compared the mortality
      rate of adults with HIV released from incarceration with the general US and
      Connecticut populations, and modelled time-to-death from any cause after prison
      release with Cox proportional hazard models. FINDINGS: We identified 1350 people
      with HIV who were released after 24 h or more of incarceration between 2007 and
      2014, of whom 184 (14%) died after index release; median age was 45 years (IQR 39
      50) and median follow-up was 5.2 years (IQR 3.0-6.7) after index release. The
      crude mortality rate for people with HIV released from incarceration was 2868
      deaths per 100 000 person-years, and the standardised mortality ratio showed that
      mortality was higher for this cohort than the general US population (6.97, 95% CI
      5.96-7.97) and population of Connecticut (8.47, 7.25-9.69). Primary cause of
      death was reported for 170 individuals; the most common causes were HIV/AIDS (78
      [46%]), drug overdose (26 [15%]), liver disease (17 [10%]), cardiovascular
      disease (16 [9%]), and accidental injury or suicide (13 [8%]). Black race
      (adjusted hazard ratio [HR] 0.52, 95% CI 0.34-0.80), having health insurance
      (0.09, 0.05-0.17), being re-incarcerated at least once for 365 days or longer
      (0.41, 0.22-0.76), and having a high percentage of re-incarcerations in which
      antiretroviral therapy was prescribed (0.08, 0.03-0.21) were protective against
      mortality. Positive predictors of time-to-death were age (>=50 years; adjusted HR
      3.65, 95% CI 1.21-11.08), lower CD4 count (200-499 cells per MUL, 2.54, 1.50
      4.31; <200 cells per MUL, 3.44, 1.90-6.20), a high number of comorbidities (1.86,
      95% CI 1.23-2.82), virological failure (2.76, 1.94-3.92), and unmonitored viral
      load (2.13, 1.09-4.18). INTERPRETATION: To reduce mortality after release from
      incarceration in people with HIV, resources are needed to identify and treat HIV,
      in addition to medical comorbidities, psychiatric disorders, and substance use
      disorders, during and following incarceration. Policies that reduce incarceration
      and support integrated systems of care between prisons and communities could have
      a substantial effect on the survival of people with HIV. FUNDING: US National
      Institutes of Health.

PMID- 30197102
TI  - Lessons from HIV deaths after incarceration.

PMID- 30197103
TI  - Alterations in body lean angle in lame horses before and after diagnostic
      analgesia in straight lines in hand and on the lunge.
AB  - Altered body lean has been subjectively observed during lungeing in lame horses.
      The objectives were to quantify the influence of lameness on body lean in trot on
      the lunge and to investigate the influence of improvement in lameness on the
      differences in body lean between reins. Thirteen lame horses were trotted in
      straight lines and lunged on a 10m-diameter circle on both reins before and after
      lameness was subjectively substantially improved by diagnostic analgesia. A
      global position system-aided inertial measurement unit attached to the tubera
      sacrale quantified body lean. Differences between reins in body lean before and
      after diagnostic analgesia were calculated and means were determined. Five and
      eight horses had unilateral and bilateral hindlimb lameness, respectively. Two of
      five horses with unilateral and three of eight horses with bilateral lameness
      leaned more on the rein with the lame or lamer hindlimb on the inside of the
      circle (difference between reins 5-8 degrees ). Two of five horses with
      unilateral and two of eight horses with bilateral lameness leaned more on the
      rein with the lame or lamer hindlimb on the outside of the circle (4-10 degrees
      ). Four horses, one with unilateral and three with bilateral lameness, had only 1
      degrees  difference in body lean angle between left and right reins. When
      lameness was improved by diagnostic analgesia, the body lean changed
      significantly towards similar leaning on left and right reins (mean angle changed
      from 8.8 degrees  to 10.0 degrees  (P=0.03) on one rein and 13.4 degrees  to 10.8
      degrees  (P=0.002) on the other rein). It was concluded that body lean becomes
      more symmetrical between reins after improvement in lameness using diagnostic
      analgesia.

PMID- 30197104
TI  - Quantifying the beliefs of key players in the UK sheep industry on the efficacy
      of two treatments for footrot.
AB  - Clinical trials have demonstrated that sheep with footrot treated with parenteral
      and topical antibiotics without foot trimming (treatment A), cure faster than
      sheep treated with foot trimming and topical antibiotics (treatment B). We
      investigated how key players in the UK sheep industry recommended treating
      footrot, and tested whether reviewing the evidence surrounding treatment of
      footrot changed their beliefs. Eight key players attended a workshop to
      investigate their current practices, and their perceived efficacy of treatments,
      using probabilistic elicitation. At the start of the study, all participants
      recommended use of antibiotic injection but only four recommended not foot
      trimming feet with footrot. Initial beliefs in the difference in cure rate within
      five days of treatment ranged from 30 to 97% in favour of treatment A (true
      difference 60%); this heterogeneity reduced after reviewing the evidence.
      Participants who believed the cure rate differed by >60% over-estimated the cure
      rate of treatment A whilst participants who believed the difference was <60% over
      estimated the efficacy of treatment B. During discussions, participants stated
      that parenteral antibiotics had always been recommended as a treatment for
      footrot but that the new research clarified when to use them. In contrast, it was
      highly novel to hear that foot trimming was detrimental to recovery, and key
      players and farmers are taking longer to accept this evidence. Three months after
      the workshop, two participants stated that they now placed greater emphasis on
      rapid individual antibiotic treatment of lame sheep and one was no longer
      recommending trimming feet.

PMID- 30197105
TI  - Implantable biosensors and their contribution to the future of precision
      medicine.
AB  - Precision medicine can be defined as the prevention, investigation and treatment
      of diseases taking individual variability into account. There are multiple ways
      in which the field of precision medicine may be advanced; however, recent
      innovations in the fields of electronics and microfabrication techniques have led
      to an increased interest in the use of implantable biosensors in precision
      medicine. Implantable biosensors are an important class of biosensors because of
      their ability to provide continuous data on the levels of a target analyte; this
      enables trends and changes in analyte levels over time to be monitored without
      any need for intervention from either the patient or clinician. As such,
      implantable biosensors have great potential in the diagnosis, monitoring,
      management and treatment of a variety of disease conditions. In this review, we
      describe precision medicine and the role implantable biosensors may have in this
      field, along with challenges in their clinical implementation due to the host
      immune responses they elicit within the body.

PMID- 30197106
TI  - Randomised clinical trial comparing clinically relevant sedation outcome measures
      in dogs after intramuscular administration of medetomidine in combination with
      midazolam or butorphanol for routine diagnostic imaging procedures.
AB  - The aim of this study was to investigate the sedative effects of medetomidine in
      combination with midazolam or butorphanol for routine imaging procedures in dogs.
      Eighty client owned dogs were recruited in a prospective, randomised, blinded
      clinical study and randomly assigned to receive one of four treatments
      intramuscularly (IM): (1) 30MUg/kg medetomidine (Med30); (2) 20MUg/kg
      medetomidine combined with 0.3mg/kg butorphanol (Med20But0.3); (3) 20MUg/kg
      medetomidine combined with 0.3mg/kg midazolam (Med20Mid0.3); and (4) 10MUg/kg
      medetomidine combined with 0.3mg/kg midazolam (Med10Mid0.3). The level of
      sedation was evaluated using a composite sedation scale assessed by one
      investigator (0=no sedation, 15=profound sedation). The number of dogs deemed to
      be adequately clinically sedated and the dose of propofol administered as rescue
      sedation were recorded. Mean+/-standard deviation sedation scores at 30min after
      the commencement of treatment in the groups that received Med20But0.3 (9.8+/-4)
      and Med20Mid0.3 (8.9+/-4.4) were not statistically significantly different from
      each other, but were significantly different from the group receiving Med10Mid0.3
      (5.6+/-3.6). Only Med20But0.3 was significantly associated with adequate clinical
      sedation, while Med10Mid0.3 was associated with 85% sedation failure. The rescue
      sedation dose of propofol (1.5+/-1mg/kg) for the Med10Mid0.3 group was
      significantly higher than for other treatments. A sedation score>=10 out of 15
      was a satisfactory cut-off to predict adequate clinical sedation. In healthy
      dogs, the combination of medetomidine with midazolam did not provide comparable
      sedation to the same dose of medetomidine in combination with butorphanol in a
      clinical setting.

PMID- 30197107
TI  - Functional anatomy of the equine temporomandibular joint: Histological
      characteristics of the articular surfaces and underlining tissues.
AB  - It has been assumed that dental conditions cause disorders of the equine
      temporomandibular joint (TMJ), due to biomechanical overload or aberrant loading.
      However, the incidence of published TMJ disorders in horses is low and this leads
      to the question whether the equine TMJ is adapted well to its biomechanical
      requirements or is able to remodel its articular surfaces in response to modified
      loading conditions. The aim of this study was to determine the histological
      characteristics of healthy equine TMJs. The tissue components of the articular
      surfaces of 10 TMJs obtained from horses without any clinical history of dental
      or TMJ disorders were analysed. Apart from the mandibular fossa of the temporal
      bone, the osseous aspects of the TMJ exhibited a uniform zoning pattern. The
      articular surfaces were composed of three tissue layers: (1) a superficial cell
      rich dense connective tissue layer; (2) a middle fibrocartilage layer; and (3) a
      deep hyaline-like cartilage layer. The articular disc was composed of an inner
      core of fibrocartilage and hyaline-like cartilage meshwork covered with both cell
      rich dense connective tissue and fibrocartilage at its dorsal and ventral
      aspects. In contrast, the mandibular fossa was only covered by a dense connective
      tissue, frequently supplemented by a synovial membrane, suggesting low
      biomechanical stress. Glycosaminoglycans, which are indicative of compressive
      loads, were predominantly present within the rostral part of the articular
      tubercle and the retroarticular process, the dorsal part of articular disc and
      the entire mandibular head, but were absent within the mandibular fossa. The
      results of this study suggest the presence of different biomechanical demands in
      the dorsal and ventral compartment of the equine TMJ.

PMID- 30197108
TI  - Pain sensitivity and injury associated with three methods of disbudding goat
      kids: Cautery, cryosurgical and caustic paste.
AB  - Pain sensitivity and skull/brain injury associated with cautery, cryosurgical and
      caustic paste disbudding were evaluated in goat kids. Kids (reared for meat;
      n=280) were randomly assigned to one of four treatments (n=70 per treatment): (1)
      sham-handling (SHAM) or (2) cautery (CAUT), (3) cryosurgical (CRYO) or (4)
      caustic paste (CASP) disbudding. A pain sensitivity test was carried out 15min
      pre-treatment and 1h post-treatment. Skull/brain injury was assessed at post
      mortem examination. Kids with evidence of injury to the skull/brain, as well as a
      random sample of kids (n=15 per treatment) without evidence of skull/brain
      injury, were selected for histological examination of brain tissue. Average daily
      gains (ADG) were calculated from body weight measurements taken 10min pre
      treatment and then at 2, 7 and 14days post-treatment as a measure of the
      potential effects of pain or injury on growth. CASP and CRYO kids displayed
      higher pain sensitivity post-treatment than CAUT or SHAM kids, suggesting that
      they experienced more acute pain 1h post-treatment. One of 70 CAUT kids had a
      perforated skull, but there was no histological evidence of brain injury in this
      animal; a further nine CAUT kids exhibited hyperaemia of the skull. The other
      treatments did not result in injury to the skull/brain. There was no evidence of
      a difference in ADG across treatments. Caustic paste and cryosurgical disbudding
      resulted in greater acute pain sensitivity than cautery disbudding; however,
      cautery disbudding has the potential to cause skull injury if performed
      incorrectly.

PMID- 30197109
TI  - Risk factors associated with beef cattle losses on intensive fattening farms in
      Austria, Germany and Italy.
AB  - The aim of this study was to investigate management and feeding practices
      associated with on-farm loss rate (mortality) on 63 beef cattle farms in Austria,
      Germany and Italy with housing systems other than fully slatted pens. Information
      on mortality and 56 categorised factors relating to the cleanliness of animal
      facilities, health and feeding management, animal-human interaction, cattle
      transport and origin were gathered during on-farm visits. Samples of total mixed
      rations (TMRs) were collected and analysed for chemical composition and particle
      size distribution. Twenty-eight categorised factors were removed from the initial
      56 due to exclusion criteria (missing data>=20% and/or monolevel factors
      with>=80% answers in one category). Mortality was the response variable in the
      risk factor analysis and the remaining 10 continuous covariates from TMR analyses
      and 28 categorised factors were independent predictors. Mean (+/-standard
      deviation) mortality, representing the proportion of dead, euthanased and early
      culled animals over the total number of animals bought in or reared in the
      previous year, was 2.8+/-3.5%. Fourteen factors were significantly associated
      with mortality in the bivariable analyses; seven factors were not considered
      further in the multivariable analysis due to collinearity. None of the factors
      related to TMR were associated with mortality. Four categorical factors,
      referring to biosecurity measures and management, were retained in the final
      multivariable model, with country effect. Buying cattle from only one farm, no
      mixing of animals during transport, presence of a dedicated sick pen and keeping
      production records were associated with lower percentage mortality.

PMID- 30197110
TI  - Shelter-housed cats show no evidence of faecal shedding of canine parvovirus DNA.
AB  - Canine parvovirus (CPV) and feline panleukopenia virus (FPV) are
      deoxyriboncucleic acid (DNA) viruses in the taxon Carnivore protoparvovirus 1.
      Exposure of cats to either CPV or FPV results in productive infection and faecal
      shedding of virus. Asymptomatic shedding of CPVs by one-third of shelter-housed
      cats in a UK study suggests that cats may be an important reservoir for
      parvoviral disease in dogs. The aim of this cross-sectional study was to
      determine the prevalence of faecal shedding of CPVs in asymptomatic shelter
      housed cats in Australia. Faecal samples (n=218) were collected from cats housed
      in three shelters receiving both cats and dogs, in Queensland and NSW. Molecular
      testing for Carnivore protoparvovirus 1 DNA was performed by polymerase chain
      reaction (PCR) amplification followed by DNA sequencing of the VP2 region to
      differentiate CPV from FPV. Carnivore protoparvovirus 1 DNA was detected in only
      four (1.8%, 95% confidence interval 0.49-4.53%) faecal samples from a single
      shelter. Sequencing identified all four positive samples as FPV. Faecal shedding
      of CPV by shelter-cats was not detected in this study. While the potential for
      cross-species transmission of CPV between cats and dogs is high, this study found
      no evidence of a role for cats in maintaining CPV in cat and dog populations
      through faecal shedding in the regions tested.

PMID- 30197111
TI  - Assessment of quality of life and chronic pain in dogs.
AB  - Assessment of chronic pain and quality of life (QOL) are integral to clinical
      veterinary research and practice, and recent years have seen an increase in the
      published tools available for the assessment of both. However, the relationship
      between chronic pain and QOL in veterinary patients has received insufficient
      attention. This narrative review for the first time explores similarities,
      differences and interactions between chronic pain and quality of life and
      identifies common challenges to their assessment in dogs. In the opinion of these
      authors, assessments of both chronic pain and quality of life should be pro
      active, global, regular, applied to answer specific questions for researchers and
      decision makers, and transparent about what has, and has not, been assessed.
      Collaboration in this field between animal welfare scientists, veterinary
      researchers and clinicians appears rare, and should be prioritised.

PMID- 30197112
TI  - Avian influenza viruses in pigs: An overview.
AB  - This paper reviews important aspects of infection of pigs with avian influenza
      viruses. Wild waterfowl are the main reservoir for influenza A viruses; other
      species, such as pigs, can be infected, but most avian strains are imperfectly
      adapted to replication and transmission in such new hosts. However, some avian-to
      porcine host jumps have resulted in the emergence of stable swine influenza virus
      lineages, with major consequences for both animal and human health. Different
      categories of factors are involved in these cross-species adaptations, both
      epidemiological (relating to host-host interactions) and virological (relating to
      host-virus interactions). An understanding of the adaptation of avian influenza
      viruses to pigs has benefited from a number of recent studies, but more research
      is warranted to fully appreciate the key molecular and epidemiological factors
      involved in this intriguing viral host jump.

PMID- 30197113
TI  - The use of time-domain analysis on the choice of measurement location for pulse
      diagnosis research: A pilot study.
AB  - BACKGROUND: Pulse diagnosis researches acquiring pulse waves from the wrist
      radial artery has not yet addressed the issue of whether this information is
      affected by differences in the hemodynamic characteristics of pressure waves
      derived from different locations. This study aimed to clarify whether the blood
      dynamic states are identical with regard to the "three positions and nine
      indicators" () listed in traditional Chinese medicine (TCM). METHODS: A total of
      37 participants of CAD group and 20 participants of healthy group were recruited,
      and pressure pulse waves were measured at 18 locations on both hands. A
      multivariate analysis (MANOVA) was performed with a "randomized block design"
      using SPSS 22.0 and R 3.4.1 to examine the time-domain parameters that
      represented certain hemodynamic characteristics. RESULTS: In CAD group, the
      results showed significant differences (p < 0.05) among the h1, h2, h3, h1/t, and
      h3/h1 measurements of the pulse waves using different indicators at the same
      position; the h1, h2, h3, and h1/t measurements of the pulse waves at different
      positions using the indicator "Superficial"; and the h1, h2, h3, h1/t, and h3/h1
      measurements of the pulse waves at different positions using the indicator
      "Medium". In healthy group, the results showed significant differences (p < 0.05)
      among the h1, h2, h3, and h1/t measurements of the pulse waves using different
      indicators at the same position; the h1, h2, and h1/t measurements of the pulse
      waves at different positions using the same indicator. CONCLUSION: Because of the
      differences in the hemodynamic characteristics among the different positions and
      indicators, the article might provide a new opinion for future pulse diagnosis
      investigations to carefully consider the measurement location to ensure the
      completeness of the information.

PMID- 30197114
TI  - Impact of code stroke on thrombolytic therapy in patients with acute ischemic
      stroke at a secondary referral hospital in Taiwan.
AB  - BACKGROUND: Efficacy of thrombolytic therapy decreases with time elapsed from
      symptom onset. We sought to identify the impact of code stroke on the
      thrombolytic therapy. METHODS: Code stroke is activated by the emergency
      physician when a patient is eligible for thrombolytic therapy. We retrospectively
      reviewed patients with acute ischemic stroke between January 2011 and December
      2014. RESULTS: In total, 1809 patients were enrolled. Code stroke was activated
      in 233 of 351 patients arriving at the emergency room (ER) within 3 h of symptom
      onset, and in 21 patients arriving >3 h. The sensitivity, specificity, and
      positive and negative predictive values of code stroke were 76%, 46%, 72%, and
      51%, respectively. Thrombolytic therapy was provided to 58 patients, accounting
      for 3.4% of all cerebral infarcts. Code stroke was activated in 40 of these
      patients. The most common reasons for excluding thrombolytic therapy were:
      National Institute of Health Stroke Scale (NIHSS) < 6, intracranial hemorrhage
      (ICH), and age >80 years. Mean liaison-to-neurological evaluation time was only 6
      min. Code stroke activation significantly reduced all the intervals, except for
      the onset-to-ER and door-to-order times. During the 4-year study period, there
      were significant reductions of the door-to-neurology liaison time by 28 min and
      door-to-laboratory time by 22 min. The proportion of door-to-needle time within
      60 min improved from 33% in 2011 to 67% in 2014. Improved NIHSS scores during
      hospitalization were most prominent in tPA-treated patients. Symptomatic ICH
      occurred in 3.6% patients arriving within 3 h. Death occurred in 50% of patients
      received tPA treatment on family's request, and only 13% of those patients had
      favorable outcome. CONCLUSION: Code stroke is effective in reducing in-hospital
      delays. The accuracy of code stroke activation has acceptable sensitivity but low
      specificity. Rapid patient assessment by neurologists increases the number of
      patients eligible for thrombolytic therapy.

PMID- 30197115
TI  - Effect of ivabradine, a funny current inhibitor, on portal hypertensive rats.
AB  - BACKGROUND: Ivabradine is a funny current inhibitor which is administered to
      patients with congestive heart failure to reduce their heart rate (HR) and
      attenuate oxidative stress. Chronic liver diseases are characterized by portal
      hypertension and hyperdynamic circulation with tachycardia. The present study
      aimed to investigate the effect of ivabradine on portal hypertension. METHODS:
      Male Sprague-Dawley rats received partial portal vein ligation (PVL) to induce
      portal hypertension. The PVL rats were randomly allocated to receive either
      vehicle or ivabradine treatment for 10 days. Then the hemodynamic data were
      collected. The levels of oxidative stress markers and the mRNA expression of
      nitric oxide synthase (NOS) were measured in the collateral vessel, the superior
      mesentery artery and the liver. In addition, the collateral vascular
      responsiveness to arginine vasopressin (AVP) was examined in the ivabradine
      treated and vehicle-treated PVL rats. RESULTS: Treatment with ivabradine
      significantly lowered the HR (174 +/- 20 vs. 374 +/- 9 beats/min; p < 0.001) and
      the superior mesentery arterial flow (SMAf) (6.6 +/- 0.3 vs. 9.1 +/- 0.7
      mL/min/100 g BW; p = 0.005) of the PVL rats compared with the control group. The
      mean arterial pressure, cardiac index, systemic vascular resistance, portal
      pressure and serum levels of oxidative stress markers were not significantly
      affected by ivabradine treatment. In addition, the NOS expression and collateral
      vascular responsiveness to AVP were not significantly influenced by ivabradine
      treatment, either. CONCLUSION: Ivabradine reduced the HR and SMAf in PVL rats,
      which alleviated the hyperdynamic circulatory state and splanchnic hyperemia of
      portal hypertension. However, whether these effects would help alleviate portal
      hypertension-related complications requires further clinical investigations.

PMID- 30197116
TI  - Activation of Intrinsic Growth State Enhances Host Axonal Regeneration into
      Neural Progenitor Cell Grafts.
AB  - Axonal regeneration after spinal cord injury (SCI) can be enhanced by activation
      of the intrinsic neuronal growth state and, separately, by placement of growth
      enabling neural progenitor cell (NPC) grafts into lesion sites. Indeed, NPC
      grafts support regeneration of all host axonal projections innervating the normal
      spinal cord. However, some host axons regenerate only short distances into
      grafts. We examined whether activation of the growth state of the host injured
      neuron would elicit greater regeneration into NPC grafts. Rats received NPC
      grafts into SCI lesions in combination with peripheral "conditioning" lesions.
      Six weeks later, conditioned host sensory axons exhibited a significant, 9.6-fold
      increase in regeneration into the lesion/graft site compared with unconditioned
      axons. Regeneration was further enhanced 1.6-fold by enriching NPC grafts with
      phenotypically appropriate sensory neuronal targets. Thus, activation of the
      intrinsic host neuronal growth state and manipulation of the graft environment
      enhance axonal regeneration after SCI.

PMID- 30197117
TI  - Defining Lineage-Specific Membrane Fluidity Signatures that Regulate Adhesion
      Kinetics.
AB  - Cellular membrane fluidity is a critical modulator of cell adhesion and
      migration, prompting us to define the systematic landscape of lineage-specific
      cellular fluidity throughout differentiation. Here, we have unveiled membrane
      fluidity landscapes in various lineages ranging from human pluripotency to
      differentiated progeny: (1) membrane rigidification precedes the exit from
      pluripotency, (2) membrane composition modulates activin signaling transmission,
      and (3) signatures are relatively germ layer specific presumably due to unique
      lipid compositions. By modulating variable lineage-specific fluidity, we
      developed a label-free "adhesion sorting (AdSort)" method with simple cultural
      manipulation, effectively eliminating pluripotent stem cells and purifying target
      population as a result of the over 1,150 of screened conditions combining
      compounds and matrices. These results underscore the important role of tunable
      membrane fluidity in influencing stem cell maintenance and differentiation that
      can be translated into lineage-specific cell purification strategy.

PMID- 30197118
TI  - Inactivation of PLK4-STIL Module Prevents Self-Renewal and Triggers p53-Dependent
      Differentiation in Human Pluripotent Stem Cells.
AB  - Centrioles account for centrosomes and cilia formation. Recently, a link between
      centrosomal components and human developmental disorders has been established.
      However, the exact mechanisms how centrosome abnormalities influence
      embryogenesis and cell fate are not understood. PLK4-STIL module represents a key
      element of centrosome duplication cycle. We analyzed consequences of inactivation
      of the module for early events of embryogenesis in human embryonic stem cells
      (hESCs) and human induced pluripotent stem cells (hiPSCs). We demonstrate that
      blocking of PLK4 or STIL functions leads to centrosome loss followed by both p53
      dependent and -independent defects, including prolonged cell divisions,
      upregulation of p53, chromosome instability, and, importantly, reduction of
      pluripotency markers and induction of differentiation. We show that the observed
      loss of key stem cells properties is connected to alterations in mitotic timing
      and protein turnover. In sum, our data define a link between centrosome, its
      regulators, and the control of pluripotency and differentiation in PSCs.

PMID- 30197119
TI  - Rapid Mast Cell Generation from Gata2 Reporter Pluripotent Stem Cells.
AB  - Mast cells are tissue-resident immune cells. Their overgrowth/overactivation
      results in a range of common distressing, sometimes life-threatening disorders,
      including asthma, psoriasis, anaphylaxis, and mastocytosis. Currently, drug
      discovery is hampered by use of cancer-derived mast cell lines or primary cells.
      Cell lines provide low numbers of mature mast cells and are not representative of
      in vivo mast cells. Mast cell generation from blood/bone marrow gives poor
      reproducibility, requiring 8-12 weeks of culture. Here we report a method for the
      rapid/robust production of mast cells from pluripotent stem cells (PSCs). An
      advantageous Gata2Venus reporter enriches mast cells and progenitors as they
      differentiate from PSCs. Highly proliferative mouse mast cells and progenitors
      emerge after 2 weeks. This method is applicable for rapid human mast cell
      generation, and could enable the production of sufficient numbers of
      physiologically relevant human mast cells from patient induced PSCs for the study
      of mast cell-associated disorders and drug discovery.

PMID- 30197121
TI  - Application of alkaloids in reversing multidrug resistance in human cancers.
AB  - Multidrug resistance (MDR) in human cancer is one of greatest challenges in
      cancer therapy. Natural products, especially the alkaloids, exert reversed
      effects on MDR with low toxicity, by interacting with various targets. In this
      review article, we summarize the recent progress made in the research of the main
      alkaloids, including classification, function, mechanism, research status, and
      application in reversing MDR.

PMID- 30197120
TI  - Cell Surface N-Glycans Influence Electrophysiological Properties and Fate
      Potential of Neural Stem Cells.
AB  - Understanding the cellular properties controlling neural stem and progenitor cell
      (NSPC) fate choice will improve their therapeutic potential. The
      electrophysiological measure whole-cell membrane capacitance reflects fate bias
      in the neural lineage but the cellular properties underlying membrane capacitance
      are poorly understood. We tested the hypothesis that cell surface carbohydrates
      contribute to NSPC membrane capacitance and fate. We found NSPCs differing in
      fate potential express distinct patterns of glycosylation enzymes. Screening
      several glycosylation pathways revealed that the one forming highly branched N
      glycans differs between neurogenic and astrogenic populations of cells in vitro
      and in vivo. Enhancing highly branched N-glycans on NSPCs significantly increases
      membrane capacitance and leads to the generation of more astrocytes at the
      expense of neurons with no effect on cell size, viability, or proliferation.
      These data identify the N-glycan branching pathway as a significant regulator of
      membrane capacitance and fate choice in the neural lineage.

PMID- 30197123
TI  - Quercetin modulates iron homeostasis and iNOS expression of splenic macrophages
      in a rat model of iron deficiency anemia.
AB  - Iron deficiency anemia is one of the most common micronutrient deficient
      conditions around the globe with various consequences, including the weakened
      immune system. Quercetin is widely distributed bioflavonoid; it has been debated
      for its dual roles in iron regulation. Quercetin-iron interaction in the body is
      a complex mechanism which has not been completely understood. The present study
      aimed to investigate the effect of quercetin on iron supplementation in iron
      deficiency anemia and on iNOS expression in splenic macrophages. The rat model of
      iron deficiency anemia was induced by feeding low iron diet to weanling rats for
      20 days. The animals were then administered with ferrous sulfate, quercetin, and
      their combination for 30 days. Blood parameters, histopathological analysis, iron
      storage, CD68, iNOS and SLC40 expression in rat spleen were investigated. Our
      results showed that quercetin regulated iron absorption, despite SLC40 down
      expression, indicating possible alternate route of iron transport, and that
      quercetin modulated iNOS production in splenic macrophages.

PMID- 30197122
TI  - Hypolipidemic effect of SIPI-7623, a derivative of an extract from oriental
      wormwood, through farnesoid X receptor antagonism.
AB  - Farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily of
      ligand-activated transcription factors. As a metabolic regulator, FXR plays key
      roles in bile acid and cholesterol metabolism and lipid and glucose homeostasis.
      Therefore, FXR is a potential drug target for several metabolic syndromes,
      especially those related to lipidemia disorders. In the present study, we
      identified small molecule SIPI-7623, a derivative of an extract from Oriental
      wormwood (Artemisia capillaris), and found that it specifically upregulated the
      expression of cholesterol-7-alpha-hydroxylase (CYP7A1), downregulated the
      expression of sterol-regulatory element-binding protein 1c (SREBP-1c) in the
      liver, and inhibited the expression of ileal bile acid binding-protein (IBABP) in
      the ileum of rats. We found that inhibition of FXR by SIPI-7623 decreased the
      level of cholesterol and triglyceride. SIPI-7623 reduced the levels of
      cholesterol and triglyceride in in vitro HepG2 cell models, ameliorated diet
      induced atherosclerosis, and decreased the serum lipid content on rats and
      rabbits model of atherosclerosis in vivo. Furthermore, SIPI-7623 decreased the
      extent of atherosclerotic lesions. Our resutls demonstrated that antagonism of
      the FXR pathway can be employed as a therapeutic strategy to treat metabolic
      diseases such as hyperlipidemia and atherosclerosis. In conclusion, SIPI-7623
      could be a promising lead compound for development of drugs to treat
      hyperlipidemia and atherosclerosis.

PMID- 30197124
TI  - Global gene expression analysis in liver of db/db mice treated with catalpol.
AB  - Catalpol, a major bioactive component from Rehmannia glutinosa, which has been
      used to treat diabetes. The present study was designed to elucidate the anti
      diabetic effect and mechanism of action for catalpol in db/db mice. The db/db
      mice were randomly divided into six groups (10/group) according to their blood
      glucose levels: db/db control, metformin (positive control), and four dose levels
      of catalpol treatment (25, 50, 100, and 200 mg.kg-1), and 10 db/m mice were used
      as the normal control. All the groups were administered orally for 8 weeks. The
      levels of fasting blood glucose (FBG), random blood glucose (RBG), glucose
      tolerance, insulin tolerance, and glycated serum protein (GSP) and the globe gene
      expression in liver tissues were analyzed. Our results showed that catalpol
      treatment obviously reduced water intake and food intake in a dose-dependent
      manner. Catalpol treatment also remarkably reduce fasting blood glucose (FBG) and
      random blood glucose (RBG) in a dose-dependent manner. The RBG-lowering effect of
      catalpol was better than that of metformin. Furthermore, catalpol significantly
      improved glucose tolerance and insulin tolerance via increasing insulin
      sensitivity. Catalpol treatment significantly decreased GSP level. The
      comparisons of gene expression in liver tissues among normal control mice, db/db
      mice and catalpol treated mice (200 and 100 mg.kg-1) indicated that there were
      significant increases in the expressions of 287 genes, whichwere mainly involved
      in lipid metabolism, response to stress, energy metabolism, and cellular
      processes, and significant decreases in the expressions of 520 genes, which were
      mainly involved in cell growth, death, immune system, and response to stress.
      Four genes expressed differentially were linked to glucose metabolism or insulin
      signaling pathways, including Irs1 (insulin receptor substrate 1), Idh2
      (isocitrate dehydrogenase 2 (NADP+), mitochondrial), G6pd2 (glucose-6-phosphate
      dehydrogenase 2), and SOCS3 (suppressor of cytokine signaling 3). In conclusion,
      catalpol ecerted significant hypoglycemic effect and remarkable therapeutic
      effect in db/db mice via modulating various gene expressions.

PMID- 30197125
TI  - 1-Methoxycarbony-beta-carboline from Picrasma quassioides exerts anti-angiogenic
      properties in HUVECs in vitro and zebrafish embryos in vivo.
AB  - Angiogenesis is a crucial process in the development of inflammatory diseases,
      including cancer, psoriasis and rheumatoid arthritis. Recently, several alkaloids
      from Picrasma quassioides had been screened for angiogenic activity in the
      zebrafish model, and the results indicated that 1-methoxycarbony-beta-carboline
      (MCC) could effectively inhibit blood vessel formation. In this study, we further
      confirmed that MCC can inhibit, in a concentration-dependent manner, the
      viability, migration, invasion, and tube formation of human umbilical vein
      endothelial cells (HUVECs) in vitro, as well as the regenerative vascular
      outgrowth of zebrafish caudal fin in vivo. In the zebrafish xenograft assay, MCC
      inhibited the growth of tumor masses and the metastatic transplanted DU145 tumor
      cells. The proteome profile array of the MCC-treated HUVECs showed that MCC could
      down-regulate several angiogenesis-related self-secreted proteins, including ANG,
      EGF, bFGF, GRO, IGF-1, PLG and MMP-1. In addition, the expression of two key
      membrane receptor proteins in angiogenesis, TIE-2 and uPAR, were also down
      regulated after MCC treatment. Taken together, these results shed light on the
      potential therapeutic application of MCC as a potent natural angiogenesis
      inhibitor via multiple molecular targets.

PMID- 30197126
TI  - Two new C21 steroidal glycosides isolated from Cynanchum komarovii.
AB  - The present study was designed to further investigate the C21 steroidal
      glycosides in Cynanchum plants. Two new steroidal glycosides based on a 13,
      14:14, 15-disecopregnane-type aglycone, komaroside P (1) and komaroside Q (2),
      together with three known compounds (3-5) were isolated from the whole herbs of
      Cynanchum komarovii. The aglycones of compounds 1 and 2 were two new
      disecopregnane. Their structures were elucidated on the basis of 1D, 2D NMR
      spectroscopic data and acid hydrolysis. All the compounds (1-5) showed potent
      inhibitory activities against human leukemia cell lines (HL-60) with IC50 values
      ranging from 16.6 to 26.3 MUmol.L-1, compared to the positive control 5
      fluorouracil (6.4 MUmol.L-1).

PMID- 30197127
TI  - New flavonoids and methylchromone isolated from the aerial parts of Baeckea
      frutescens and their inhibitory activities against cyclooxygenases-1 and -2.
AB  - In the present study, we carried out a phytochemical investigation of the ethanol
      extract of the aerial parts of Baeckea frutescens, which resulted in the
      isolation of two new flavonoid glycosides, myricetin 3-O-(5"-O-galloyl)-alpha-L
      arabinofuranoside (1), 6-methylquercetin 7-O-beta-D-glucopyranoside (2), one new
      methylchromone glycoside, 7-O-(4', 6'-digalloyl)-beta-D-glucopyranosyl-5-hydroxy
      2-methylchromone (3), together with three known compounds (4-6). The structures
      of these isolated compounds were established on the basis of 1D and 2D NMR
      techniques and chemical methods. The anti-inflammatory activities of the
      compounds 1-6 were evaluated for their inhibitory effects against cyclooxygenases
      1 and -2 in vitro. Compounds 1-6 showed potent COX-1 and COX-2 inhibiting
      activities in vitro with IC50 values ranging from 1.95 to 5.54 MUmol.L-1 and
      ranging from 1.01 to 2.27 MUmol.L-1, respectively.

PMID- 30197128
TI  - Novel sesquiterpenoids isolated from Chimonanthus praecox and their antibacterial
      activities.
AB  - In the present study, four new sesquiterpenoids, chimonols A-D (compounds 1-4),
      together with four known compounds (5-8) were isolated from the EtOAc extract of
      Chimonanthus praecox Link. The structures of these new compounds were elucidated
      on the basis of spectroscopic techniques (UV, IR, MS, and 1D and 2D NMR), and
      their absolute configurations were established by comparing experimental and
      calculated electronic circular dichroism (ECD) spectra. Compounds 1-8 were
      evaluated for antimicrobial activities and the minimum inhibitory concentrations
      (MICs) were determined by the broth microdilution method in 96-well culture
      plates. Compounds 1, 2, and 7 exhibited weak antibacterial effects for S. aureus
      (ATCC 6538), E. coli (ATCC 11775), and P. aeruginosa (ATCC 10145) with MIC values
      being 158-249 ug.mL-1. Compounds 3-7 showed activities against C. glabrata (ATCC
      2001) and S. aureus (ATCC 43300) with MIC values being 128-197 ug.mL-1. Compounds
      1-4 showed activity against S. aureus (ATCC 25923) with MIC values being 162-254
      ug.mL-1. The present study provided a basis for future evaluation of these
      compounds as antibacterial agents.

PMID- 30197129
TI  - Metabonomics delineates allergic reactions induced by Shuang-huang-lian injection
      in rats using ultra performance liquid chromatography-mass spectrometry.
AB  - Shuang-huang-lian Injection (SHLI) is the first successfully developed drug from
      traditional Chinese medicine (TCM) powder for injection, since its use for the
      treatment of acute respiratory tract infection, pneumonia, influenza, etc. At the
      same time, its allergic reactions have also emerged, which limits clinical
      applications. However, few scholars pay attention to the mechanism of allergic
      reactions. In this present study, metabonomics technology was used to explore the
      changes in endogenous metabolites in urine of the rat model of SHLI induced
      allergic reaction; we and analyzed the metabolites, metabolic pathway, and the
      mechanism which were closely related to the allergic reactions. The levels of
      serum histamine and tryptase were examined and changes in histomorphology were
      also observed. Based on the UPLC-Q-TOF/MS metabonomics, we carried out the
      pattern recognition analysis, selected potential biomarkers associated with
      allergic reactions, and explored the pathological mechanism for SHLI induced
      allergic reaction, which laid the foundation for the safety research of SHLI. Our
      results showed that SHLI increased the levels of serum histamine and tryptase in
      rats with allergic reaction; we determined 15 biomarkers in rat allergic reaction
      model induced by SHLI and found multiple metabolic pathways involved, such as
      metabolism of linolenic acid, phenylalanine, amino acid, 2-oxo acid, and purine
      and other metabolic pathways.

PMID- 30197130
TI  - Does chronic caregiving stress accelerate T cell immunosenescence?

PMID- 30197131
TI  - Effect of concentrate level on enteric methane emissions, production performance,
      and rumen fermentation of Jersey cows grazing kikuyu-dominant pasture during
      summer.
AB  - The effect of concentrate feeding level on enteric CH4 emissions from cows
      grazing medium quality summer pasture is yet to be investigated. Sixty
      multiparous Jersey cows (9 rumen-cannulated) were used in a randomized complete
      block design study (with the cannulated cows in a 3 * 3 Latin square design) to
      investigate the effect of concentrate feeding level (0, 4, and 8 kg/cow per day;
      as-fed basis) on enteric CH4 emissions, production performance, and rumen
      fermentation of dairy cows grazing summer pasture (17 cows plus 3 cannulated cows
      per treatment). Enteric CH4 emissions were measured from 11 cows per treatment
      group during one 7-d measurement period using the sulfur hexafluoride tracer gas
      technique. Pasture dry matter intake (DMI) was determined parallel with the CH4
      measurement period using TiO2 as an external marker, and milk yield, milk
      composition, cow condition, and pasture pre- and postgrazing measurements were
      also recorded. Daily total DMI (11.2 to 15.6 kg/cow), milk yield (9.1 to 18.2
      kg/cow), energy-corrected milk (ECM; 11.2 to 21.6 kg/cow), and milk lactose
      content (44.1 to 46.7 g/kg) increased linearly, whereas pasture DMI (11.2 to 8.4
      kg/cow) decreased linearly with increasing concentrate feeding level. Daily CH4
      production (323 to 378 g/d) increased linearly due to the increase in total DMI,
      whereas CH4 yield (29.1 to 25.1 g/kg of DMI) and CH4 intensity (35.5 to 21.1 g/kg
      of milk yield; and 28.8 to 17.6 g/kg of ECM) decreased linearly with increasing
      concentrate feeding level. Diurnal ruminal pH (6.45 to 6.32) and in sacco DM and
      neutral detergent fiber disappearance decreased linearly. Acetic and propionic
      acid were unaffected by treatment, whereas butyric acid (5.21 to 6.14 mM)
      increased linearly and quadratically with increasing concentrate feeding level.
      It was concluded that a high concentrate feeding level not only increases animal
      efficiency but is moreover a viable CH4 mitigation option for dairy cows grazing
      kikuyu-dominant pasture in late summer when pasture is inherently fibrous.

PMID- 30197132
TI  - Methane production, rumen fermentation, and diet digestibility of Holstein and
      Jersey dairy cows being divergent in residual feed intake and fed at 2 forage-to
      concentrate ratios.
AB  - Improving feed efficiency of dairy cows through breeding is expected to reduce
      enteric methane production per unit of milk produced. This study examined the
      effect of 2 forage-to-concentrate ratios on methane production, rumen
      fermentation, and nutrient digestibility in Holstein and Jersey dairy cows
      divergent in residual feed intake (RFI). Before experimental onset, RFI was
      estimated using a random regression model on phenotypic herd data. Ten lactating
      Holstein and 10 lactating Jersey cows were extracted from the herd and allocated
      to a high or low pre-experimental RFI group of 5 animals each within breed. Cows
      were fed ad libitum with total mixed rations either low (LC) or high (HC) in
      concentrates during 3 periods in a crossover design with a back-cross and
      staggered approach. Forage-to-concentrate ratio was 68:32 for LC and 39:61 for
      HC. Cows adapted to the diets in 12 to 24 d and feces were subsequently collected
      on 2 d. Afterward, gas exchange was measured in respiration chambers and rumen
      liquid was collected once after cows exited the chambers. Pre-experimental RFI
      was included in the statistical analysis as a class (low and high RFI) or
      continuous variable. Methane per kilogram of dry matter intake (DMI) was lower
      for Holsteins than Jerseys and the response to increased concentrate level was
      more pronounced for Holsteins than Jerseys (27.2 vs.13.8%); a similar pattern was
      found for the acetate:propionate ratio. However, methane production per kilogram
      of energy-corrected milk (ECM) was unaffected by breed. Further, total-tract
      digestibility of neutral detergent fiber was higher for Jerseys than Holsteins.
      For RFI as a class variable, DMI, methane production regardless of the
      expression, and digestibility were unaffected by RFI. For RFI as a continuous
      variable, DMI was lower and methane per kilogram of DMI was higher for cows with
      negative (efficient) than positive (inefficient) RFI values, and neutral
      detergent fiber digestibility was higher for Holsteins with negative than
      positive RFI values, but not for Jerseys. Daily methane production and methane
      per kilogram of ECM were unaffected by RFI. In conclusion, methane per kilogram
      of DMI of Jerseys was lowered to a smaller extent in response to the HC diet than
      of Holsteins. When pre-experimental RFI was used as a continuous variable, higher
      methane per kilogram of DMI was found for cows with negative RFI than positive
      RFI values, but not for methane per kilogram of ECM. These findings call for
      validation in larger studies.

PMID- 30197133
TI  - Particle size and endosperm type of dry corn grain altered duodenal flow of B
      vitamins in lactating dairy cows.
AB  - The objective of the experiment was to determine if factors such as endosperm
      type (floury vs. vitreous) and particle size (fine vs. medium) of dry corn grain,
      known to affect starch digestibility in the rumen, modify apparent ruminal
      synthesis and duodenal flow of B vitamins in lactating dairy cows. Eight
      lactating multiparous Holstein cows equipped with rumen and duodenal cannulas
      were assigned randomly to a treatment sequence according to a 2 * 2 factorial
      arrangement in duplicate 4 * 4 Latin square design experiment. Duration of each
      experimental period was 21 d. When expressed per unit of dry matter intake (DMI),
      floury treatments increased duodenal flow and apparent ruminal synthesis of
      niacin and folates but tended to increase apparent degradation of thiamin in the
      rumen. Duodenal flow of thiamin, riboflavin, niacin, folates, and vitamin B12,
      expressed per unit of DMI, decreased with an increase in particle size.
      Similarly, apparent degradation of thiamin and riboflavin was greater and
      apparent synthesis of niacin, folates, and vitamin B12 was reduced when cows were
      fed coarser dry corn grain particles. Neither endosperm type nor particle size
      had an effect on duodenal flow and apparent ruminal synthesis of vitamin B6.
      Apparent ruminal syntheses, expressed per unit of DMI, of all studied B vitamins
      but thiamin were negatively correlated with apparent ruminal digestibility of
      neutral detergent fiber. Duodenal flow of microbial N was positively correlated
      with apparent ruminal synthesis of riboflavin, niacin, vitamin B6, and folates.
      Under the conditions of the present experiment, except for thiamin, the effects
      of factors increasing starch digestibility of dry corn grain in the rumen on the
      amounts of B vitamins available for absorption by the dairy cow seem to be
      mediated through differences on ruminal digestibility of neutral detergent fiber
      and, to a lesser extent, on duodenal microbial N flow.

PMID- 30197134
TI  - Associations between the general condition of culled dairy cows and selling price
      at Ontario auction markets.
AB  - Dairy cows are culled from the herd for a variety of reasons, the most common
      being fertility problems, low milk production, or udder problems. Disease and
      injury can contribute to the decision to cull either directly, or indirectly, by
      causing fertility or production problems, leading to culling. Disease or injury
      may also affect the cow's ability to handle the stress of transportation and may
      increase the risk for reduced welfare. The purpose of this study was to determine
      the general condition of culled dairy cows sold at Ontario auction markets, to
      quantify the frequency of culled cows in poor condition sold at these auctions,
      and to determine how this relates to the sale price of the cow. Data were
      collected on 4,460 culled dairy cows, sold at 3 Ontario auction markets, over a
      continuous 16-wk study period. Observers assessed the general condition of dairy
      cows entering the sales ring by recording each individual cow's hock injury
      score, body condition score (BCS), gait score, and tail score, in accordance with
      2017 Canadian proAction Animal Care guidelines. Each cow's body weight, breed,
      and sale price were also recorded. Results showed that 27.2% of culled cows
      scored had unacceptable hock injuries, 40.5% had a BCS <=2, 72.7% had an abnormal
      gait, and 12.5% had docked tails. Culled cows with a BCS <=2 sold for $0.20
      less/kg compared with those with a BCS >2, which equated to an overall average
      loss of $117 per cow. Cows with an abnormal gait sold for $0.05 less/kg compared
      with culled cows with a normal gait, which equated to an overall average loss of
      $32.45 per cow. There was no difference in the sale price depending on hock
      injury score or the presence or absence of a full tail. The main issues
      identified in this study were the high prevalence of low body condition and
      abnormal gait, indicating that the welfare of these cows may be at risk.
      Additionally, cows with low BCS or abnormal gait sold for a lower price compared
      with cows that were in good condition, leading to reduced potential profit for
      the producer.

PMID- 30197135
TI  - Freezing point and other technological properties of milk of the Polish Coldblood
      horse breed.
AB  - Mare milk is a valued and sought-after raw material for the production of
      innovative dairy products. The high demand, low supply, high price, and lack of
      accurate characterization of the milk of a given horse breed may provoke its
      deliberate fraudulent dilution. The aim of this work was to analyze the freezing
      point against a background of various selected technological parameters of Polish
      Coldblood mare milk. Research was carried out on multiparous Polish Coldblood
      mares from 5 to 8 yr of age with live weights between 618 and 851 kg. Their milk
      was tested on d 1, 3, and 7 postpartum and once a month for the next 9 mo of
      lactation (n = 52). Milk from 13 mares, taken daily in mo 4 of lactation, was
      collected for the dilution study (n = 403). The basic composition of the milk was
      as follows: solids-not-fat, 84.4 g/kg, fat 15.1 g/kg, lactose 65.3 g/kg, and
      total protein 24.2 g/kg (made up of casein, 14.6 g/kg, and whey protein, 9.5
      g/kg). The dominant amino acids were glutamic acid, proline, leucine, and
      aspartic acid. The mean freezing point during a 9-mo lactation was -0.557 degrees
      C (coefficient of variation = -2.787; 5th to 95th percentile: -0.563 to -0.550
      degrees C). Based on our analysis, we adopted -0.550 degrees C (from 3 to 6 mo)
      as the reference value for milk from the Polish Coldblood horse. Analysis of the
      model of changes in freezing point, after dilution, using the coefficient of
      determination and Akaike's information criterion, showed that a linear model
      could be recommended (y = 79.35 + 144.35x). Addition of 1% water increased the
      freezing point of Polish Coldblood mare milk by 0.0069 degrees C.

PMID- 30197136
TI  - Short communication: Use of an ultrafiltration device in gland cistern for
      continuous sampling of healthy and mastitic quarters of lactating cattle for
      pharmacokinetic modeling.
AB  - Pharmacokinetic studies of the drugs in the milk are often limited due to
      infrequent sampling associated with milking. Alternatively, frequent sample
      collection with repeated milking may increase drug elimination. The objective of
      this study was to determine the feasibility of continuously sampling the udder
      using ultrafiltration. An ultrafiltration probe was placed into the gland
      cisterns through mammary parenchyma of normal and mastitic quarters of 6 mature
      mid-lactation Jersey cows with naturally occurring subclinical mastitis. An
      ultrafiltration probe was secured to the caudal or lateral aspect of the udder
      depending on the quarter being sampled. The timed interval samples were collected
      at 0, 2, 4, 6, 8, 12, 18, 24, 28, 32, 36, 48, 60, 72, 84, and 96 h after drug
      administration. Plasma samples were collected at the same time points. Each cow
      received 2.2 mg/kg of flunixin intravenously before milking at time 0. All cows
      were routinely milked by machine every 12 h. Flunixin concentrations in plasma,
      whole milk, and milk ultrafiltrates were analyzed by use of ultra-high
      performance liquid chromatography with mass spectrometric detection. We found no
      significant effects on the appearance of the milk or the ability to milk the cows
      after implantation of the ultrafiltration probes. The concentration of flunixin
      collected from the ultrafiltration probes in the mastitic quarters tended to be
      greater than that of the healthy quarters. We concluded that collection of
      ultrafiltration samples from the mammary gland of cows provides a viable means to
      continuously assess drug concentrations in the milk while continuing to milk the
      cow normally. This study demonstrates the utility of continuous sampling of milk
      via ultrafiltration for future pharmacokinetic studies in cattle.

PMID- 30197137
TI  - Feeding high oleic acid soybeans in place of conventional soybeans increases milk
      fat concentration.
AB  - It is well established in the literature that feeding free vegetable oils rich in
      oleic acid results in greater milk fat secretion than does feeding linoleic-rich
      oils. The objectives of these experiments were to analyze the effects of oleic
      and linoleic acid when fed in the form of full-fat soybeans and the interaction
      between soybean particle size and fatty acid (FA) profile. Soybeans were included
      in diets on an iso-ether extract basis and diets were balanced for crude protein
      using soybean meal. Experiment 1 used 63 cows (28 primiparous, PP; 35
      multiparous, MP) housed in a freestall barn with Insentec roughage intake control
      gates (Marknesse, the Netherlands). Cows were divided into 4 mixed parity groups
      within the same pen. Two groups were assigned to each of the 2 diets: whole raw
      Plenish (WP, high oleic; Dupont-Pioneer, Johnston, IA) soybeans or whole raw
      conventional (WC, high linoleic) soybeans. The MP cows exhibited significantly
      increased milk fat yield on the WP diet compared with the WC diet. A
      significantly greater C18 milk FA yield by the MP cows fed WP was observed
      compared with those fed WC, but no difference was present in the C16 or short
      chain FA yield. No effects were seen in the PP cows. Experiment 2 used 20 cows
      (10 PP, 10 MP) in 2 balanced 5 * 5 Latin squares within parity. Cows received 5
      diets: raw WP and WC diets, raw ground Plenish and conventional soybean diets (GP
      and GC, respectively), and a low fat control. A significant benefit was found for
      the GP diet compared with the GC diet for milk fat concentration and yield. In
      experiment 2, no difference was observed between cows fed the WP compared with
      the WC diet. In experiment 2, cows consuming the Plenish diets produced less milk
      than when consuming the conventional soybean diets. The soybean diets resulted in
      significantly more C18 and less <C18 FA compared with the low fat diet. The GP
      diet resulted in significantly more C18 FA than the GC diet and the ground
      soybeans resulted in less C16 FA compared with whole soybeans. In both
      experiments, cows fed the Plenish diets exhibited decreased trans-10 18:1, a FA
      often increased during milk fat depression, compared with those fed the
      conventional soybean diets, though differences were not observed in trans-10,cis
      12 conjugated linoleic acid. These results indicate that feeding whole soybeans
      rich in oleic acid may result in some increased milk fat secretion compared with
      conventional whole soybeans containing high levels of linoleic acid. This
      advantage is clear for ground high-oleic soybeans compared with ground
      conventional soybeans.

PMID- 30197138
TI  - Canadian dairy cattle veterinarian perspectives on calf welfare.
AB  - As advisors to dairy farmers, veterinarians are ideally positioned to influence
      the health of the dairy herd. Recent studies have demonstrated that dairy cattle
      veterinarians are also concerned about animal welfare, specifically on issues
      related to the housing environment, painful conditions and procedures, and
      managing disease in adult animals. However, less is known regarding their
      perspectives on calf welfare. The goal of this study was to engage cattle
      veterinarians in an in-depth discussion to gain a better understanding of what
      they think about calf welfare, and to provide clarity on what they feel is their
      responsibility to improve the welfare of dairy calves. Focus groups (n = 5), that
      collectively had 33 participants representing 5 Canadian provinces and different
      geographical regions, were conducted as part of a continuing education workshop
      for Canadian cattle veterinarians. Two trained individuals undertook exploratory
      data analysis using applied thematic analysis, where initial themes were
      identified and used to develop a detailed codebook to further guide the coding
      process. All transcripts were coded twice to test the validity of the initial
      codes and themes. Four major themes were identified: (1) veterinarians
      prioritized calf health and traded off this issue for other issues such as the
      calf's social needs; additionally, concerns included nutrition, hunger, and bull
      calf management; (2) veterinarians see their role in improving calf welfare
      within the context of shifting norms of calf management, believed to be
      consequence of pressure from within their profession, but also arising from
      pressure from their clients and the public; (3) veterinarians see their role as
      one of exerting social influence, primarily as an educator of their clients; and
      finally, (4) veterinarians see their responsibility in improving calf welfare as
      shaped by their personal values and professional ethics. Our results indicate
      that the veterinarians participating in this study are concerned about a range of
      calf welfare issues, believe they should have a more active role in calf
      management on farms, and see their role in improving calf welfare as shaped by
      their own values, the needs of their clients, and the concerns of the public.

PMID- 30197139
TI  - Method for short-term prediction of milk yield at the quarter level to improve
      udder health monitoring.
AB  - Udder health problems are often associated with milk losses. These losses are
      different between quarters, as infected quarters are affected both by systemic
      and pathogen-specific local effects, whereas noninfected quarters are only
      subject to systemic effects. To gain insight in these losses and the milk yield
      dynamics during disease, it is essential to have a reliable reference for quarter
      level milk yield in an unperturbed state, mimicking its potential yield. We
      developed a novel methodology to predict this quarter milk yield per milking
      session, using an historical data set of 504 lactations collected on a test farm
      by an automated milking system from DeLaval (Tumba, Sweden). Using a linear mixed
      model framework in which covariates associated with the linearized Wood model and
      the milking interval are included, we were able to describe quarter-level yield
      per milking session with a proportional error below 10%. Applying this model
      enables us to predict the milk yield of individual quarters 1 to 50 d ahead with
      a mean prediction error ranging between 8 and 20%, depending on the amount of
      historical data available to estimate the random effect covariates for the
      predicted lactation. The developed methodology was illustrated using 2 examples
      for which quarter-level milk losses are calculated during clinical mastitis.
      These showed that the quarter-level mixed model allows us to gain insight in
      quarter lactation dynamics and enables to calculate milk losses in different
      situations.

PMID- 30197140
TI  - Effect of the environment on the risk of respiratory disease in preweaning dairy
      calves during summer months.
AB  - Heat stress has the potential to adversely affect the physiology, passive
      immunity, and growth of preweaning dairy calves, increasing their risk of
      respiratory disease. The effect of heat stress on the risk for bovine respiratory
      disease (BRD) may be mediated in part through housing, ventilation, and
      management factors. As a result, differences may exist in meteorological measures
      recorded in the calf-rearing area (macroenvironment) and within a calf's
      enclosure (microenvironment). The objective of this prospective cohort study was
      to evaluate and compare the association between exposure to temperature and
      humidity measured at the macro- and microenvironment, and BRD in preweaning dairy
      calves; a secondary objective was to evaluate the correlation between the macro-
      and microenvironment. A cohort of 252 calves from 4 premises in central San
      Joaquin Valley, California (CA), was followed and evaluated for development of
      respiratory disease using the CA BRD scoring system for preweaning dairy calves,
      a standardized and validated scoring system. During this time, the meteorological
      conditions of the calf-rearing area and the within-hutch environment were
      measured and showed a significant correlation with regard to temperature and
      humidity. Mixed effects logistic regression and survival analysis were used to
      analyze the association between the exposures daily environmental measures of
      temperature, humidity, and temperature-humidity index (THI) and the outcome BRD,
      adjusted for dairy premises, calf age, sex, and breed. Results showed a
      significant positive association between daily maximum temperature and BRD in
      both the calf's macroenvironment [odds ratio = 1.121 (95% confidence interval
      (CI) = 1.029-1.222)] and microenvironment [odds ratio = 1.203 (95% CI = 1.020
      1.418)]. Estimated hazard rates also showed a significant positive association
      between BRD and daily maximum temperature in both the macroenvironment [hazard
      ratio = 1.127 (95% CI = 1.053-1.206)] and microenvironment [hazard ratio = 1.119
      (95% CI = 1.047-1.197)]. In contrast, we found no association between daily
      maximum humidity in a calf's microenvironment and BRD. Daily maximum THI within
      the hutch was significantly associated with only the rate of BRD cases [hazard
      ratio = 1.070 (95% CI = 1.003-1,141)] but not the odds of occurrence of BRD.
      Maximum THI is estimated using temperature and humidity, which in California's
      hot and dry summers may limit variability in THI, explaining its weaker
      significant association with risk of BRD (or lack of association with odds of
      BRD) compared with models for maximum temperature in this study. Calves exposed
      to high day temperatures and relatively low humidity may be experiencing heat
      stress that predisposes to BRD. Results of the current study suggest that heat
      abatement efforts should address heat stress at the microenvironment level to
      mitigate BRD in calves. Further research should investigate strategies to improve
      calf hutch systems, including hutch materials and design that may optimize
      ventilation, provide ample shade, spacing, cleanliness, and protection from heat.

PMID- 30197141
TI  - Genetic parameters for cheese-making properties and milk composition predicted
      from mid-infrared spectra in a large data set of Montbeliarde cows.
AB  - Cheese-making properties of pressed cooked cheeses (PCC) and soft cheeses (SC)
      were predicted from mid-infrared (MIR) spectra. The traits that were best
      predicted by MIR spectra (as determined by comparison with reference
      measurements) were 3 measures of laboratory cheese yield, 5 coagulation traits,
      and 1 acidification trait for PCC (initial pH; pH0PPC). Coefficients of
      determination of these traits ranged between 0.54 and 0.89. These 9 traits as
      well as milk composition traits (fatty acid, protein, mineral, lactose, and
      citrate content) were then predicted from 1,100,238 MIR spectra from 126,873
      primiparous Montbeliarde cows. Using this data set, we estimated the
      corresponding genetic parameters of these traits by REML procedures. A univariate
      or bivariate repeatability animal model was used that included the fixed effects
      of herd * test day * spectrometer, stage of lactation, and year * month of
      calving as well as the random additive genetic, permanent environmental, and
      residual effects. Heritability estimates varied between 0.37 and 0.48 for the 9
      cheese-making property traits analyzed. Coagulation traits were the ones with the
      highest heritability (0.42 to 0.48), whereas cheese yields and pH0 PPC had the
      lowest heritability (0.37 to 0.39). Strong favorable genetic correlations, with
      absolute values between 0.64 and 0.97, were found between different measures of
      cheese yield, between coagulation traits, between cheese yields and coagulation
      traits, and between coagulation traits measured for PCC and SC. In contrast, the
      genetic correlations between milk pH0 PPC and CY or coagulation traits were weak
      (-0.08 to 0.09). The genetic relationships between cheese-making property traits
      and milk composition were moderate to high. In particular, high levels of
      proteins, fatty acids, Ca, P, and Mg in milk were associated with better cheese
      yields and improved coagulation. Proteins in milk were strongly genetically
      correlated with coagulation traits and, to a lesser extent, with cheese yields,
      whereas fatty acids in milk were more genetically correlated with cheese yields
      than with coagulation traits. This study, carried out on a large scale in
      Montbeliarde cows, shows that MIR predictions of cheese yields and milk
      coagulation properties are sufficiently accurate to be used for genetic analyses.
      Cheese-making traits, as predicted from MIR spectra, are moderately heritable and
      could be integrated into breeding objectives without additional phenotyping cost,
      thus creating an opportunity for efficient improvement via selection.

PMID- 30197142
TI  - Behavioral changes in group-housed dairy calves infected with Mannheimia
      haemolytica.
AB  - Monitoring sickness behavior may improve identification, management, and welfare
      of sick animals. The objective of this study was to characterize components of
      sickness behavior in group-housed dairy calves, using an experimental disease
      challenge model with Mannheimia haemolytica (MH). Holstein bull calves (aged 3-7
      weeks; 58.0 +/- 12.0 kg of body weight) were group-housed based on age and body
      weight in sand-bedded pens (6 calves/pen, 6.6 m2/calf) and provided pasteurized
      waste milk (8 L/d) 2*/d and grain concentrate ad libitum. Within group, calves
      were randomly assigned to 1 of 2 treatments: (1) inoculation at the tracheal
      bifurcation with 3 * 109 cfu of MH suspended in 5 mL of sterile phosphate
      buffered saline (PBS) followed by a 120 mL wash PBS (MH; n = 12, 3/pen), or (2)
      inoculation with 5 mL + 120 mL of sterile PBS only (control; n = 12, 3/pen).
      Rectal temperature and health scores were collected from d 0 to +6 of the
      challenge. A range of behaviors, including feeding patterns and social
      interactions, were recorded from video from d 0 to +2. The challenge model
      resulted in calves experiencing a mild disease state: rectal temperatures of MH
      calves were elevated throughout the challenge compared with control calves,
      peaking at 12 h postinoculation (39.2 vs. 38.9 degrees C; standard error = 0.14).
      Many behavioral responses were subject to treatment by day effects, with calves
      generally becoming less active following inoculation with MH and then returning
      to baseline. Affected behaviors surrounding feeding included milk feeding time,
      frequency of competitive displacements, and concentrate feeding time. Lying time
      was similarly subject to treatment by day effects, and MH calves also spent more
      time lying on their left side compared with their right (604 vs. 471 min/h;
      standard error = 32), whereas control calves expressed no laterality. Duration of
      social lying did not differ, but frequency of social lying bouts decreased in MH
      calves following inoculation (0.44 vs. 0.75 bouts/h; standard error = 0.04).
      Social grooming was initiated less by MH calves (0.78 vs. 1.96 min/h; standard
      error = 0.38), but they tended to receive more social grooming for a greater
      duration of time (1.59 vs. 1.25 min/h; standard error = 0.13). Overall, we found
      that infected calves exhibited reduced grooming, feeding, and social
      interactions, suggesting that these behavioral changes may be useful indicators
      of early stages of respiratory disease.

PMID- 30197143
TI  - Detection of microRNA in cattle serum and their potential use to diagnose
      severity of Johne's disease.
AB  - Mycobacterium avium subspecies paratuberculosis (MAP) causes Johne's disease in
      ruminants, which is characterized by chronic progressive granulomatous enteritis.
      The infection leads to wasting and weight loss in the animals and eventually
      death, causing considerable production losses to the agricultural industry
      worldwide. Currently available ELISA- and PCR-based diagnostic tests have limited
      sensitivity and specificity during early MAP infection in cattle, suggesting that
      there is an urgent demand for alternative diagnostic tests. Circulating microRNA
      (miRNA) have recently gained attention as potential biomarkers for several
      diseases in humans. However, knowledge and use of miRNA as biomarkers in diseases
      of ruminants, including Johne's disease, are very limited. Here we used
      NanoString nCounter technology (NanoString, Seattle, WA), a digital platform for
      amplification-free and hybridization-based quantitative measurement of miRNA in
      the sera of noninfected and naturally MAP-infected cattle with different severity
      of infection. Using probes developed against human miRNA, 26 miRNA were detected
      in cattle serum; 13 of these miRNA were previously uncharacterized for cattle.
      Canonical discrimination analysis using 20 miRNA grouped animals into 4 distinct
      clusters based on their disease status, suggesting that the levels of these miRNA
      can reflect disease severity. A model was developed using a combination of 4
      miRNA (miR-1976, miR-873-3p, miR-520f-3p, and miR-126-3p), which distinguished
      moderate and severely infected animals from noninfected animals. Our study
      demonstrated the ability of the NanoString nCounter technology to detect
      differential expression of circulating miRNA in cattle and contributes to widely
      growing evidence that miRNA can be used as biomarkers in infectious diseases in
      cattle.

PMID- 30197144
TI  - Effects of gradual and later weaning ages when feeding high milk replacer rates
      on growth, textured starter digestibility, and behavior in Holstein calves from 0
      to 4 months of age.
AB  - The objectives of this study were to evaluate calf performance, diet
      digestibility, and behaviors when feeding 4 milk replacer (MR) programs with
      different MR rates, weaning ages, and MR reduction steps. Male Holstein calves (n
      = 96; 40 +/- 1 kg of body weight; 1 to 2 d of age) were housed in individual pens
      for 56 d. Feeding programs for MR were 0.66 kg for 35 d; then 0.33 kg for 7 d fed
      only in the a.m. (0.6 kg); 0.66 kg for 7 d, 0.82 kg for 35 d, 0.33 kg for 4 d in
      a.m. only, and 0.22 kg for 3 d in a.m. only (0.8 kg); 0.66 kg for 7 d, 0.82 kg
      for 7 d, 1.1 kg for 21 d, 0.82 kg for 7 d, 0.33 kg for 4 d in a.m. only, and 0.22
      kg for 3 d in a.m. only (1.1 kg); and ad libitum allowance for 35 d, 0.82 kg for
      7 d, 0.44 kg for 4 d in a.m. only, and 0.22 kg for 3 d in a.m. only (ad lib).
      Calves were fed a common MR [25% crude protein, 17% fat, dry matter (DM) basis].
      A textured calf starter with whole corn and oats (20% crude protein and 39%
      starch, DM basis) and water were fed for ad libitum intake during the nursery
      trial. Daily behavior duration (rumination, eating, and activity) was
      continuously recorded from d 1 to 55 for 4 calves/treatment using ear tag
      accelerometers (CowManager SensOor; Agis, Harmelen, the Netherlands). All calves
      were moved into groups by MR program (4 calves/pen) at 56 d and fed the same
      starter blended with 5% grass hay. Fecal samples were collected from individual
      calves between d 52 to 56 and from pen floors on d 66 to 70 to estimate total
      tract digestibility. Data were analyzed as a randomized complete block design
      with repeated measures when appropriate. Intake of MR averaged 25.3, 35.3, 40.9,
      and 46.5 kg of DM per calf for 0.6 kg, 0.8 kg, 1.1 kg, and ad lib treatments,
      respectively. Starter intake was greatest for 0.6 kg compared with others and
      average daily gain (ADG) differed among all 4 programs with 0.6 kg < 0.8 kg < 1.1
      kg < ad lib during d 0 to 56. Intake of MR for ad lib was highly variable and was
      reflected in ADG. Daily rumination, eating, and activity durations did not differ
      among treatments from d 1 to 55 of the nursery trial. Digestibility of DM,
      organic matter, acid and neutral detergent fiber, and sugar at d 52 to 56 were
      greater for 0.6 kg versus ad lib. Digestibility of DM at d 66 to 70 differed for
      all treatments with 0.6 kg > 0.8 kg > 1.1 kg > ad lib and was mostly influenced
      by fiber digestibility. During the grower trial (d 56 to 112), ADG was greater
      for 0.6 kg versus 1.1 kg and ad lib. Hip width change was greater for 0.6 kg
      versus other treatments. Feeding more than 0.6 kg/d of MR increased ADG
      preweaning, but reduced diet digestibility postweaning resulted in similar calf
      BW and frame size by 4 mo of age among MR feeding programs.

PMID- 30197145
TI  - Level of circulating concentrations of progesterone during ovulatory follicle
      development affects timing of pregnancy loss in lactating dairy cows.
AB  - The objective of this experiment was to determine the effect of high versus low
      progesterone (P4) during the pre-dominance or dominance phase (or both) of
      ovulatory follicle development on follicular dynamics and fertility of lactating
      dairy cows. Progesterone (P4) was manipulated to reach high (H) or low (L) serum
      concentrations during the pre-dominance phase (d 0 to 4 of the wave) and
      dominance phase (d 5 to 7 of the wave) of a second follicular wave ovulatory
      follicle, creating 4 treatments: H/H, H/L, L/H, and L/L. Luteolysis was induced
      with PGF2alpha on d 7 of the wave and ovulation was induced with GnRH 56 h after
      PGF2alpha. Cows (n = 558) received artificial insemination (AI) 16 h following
      GnRH. Pregnancy was determined at 6 intervals during gestation and at calving to
      quantify pregnancy loss beginning at d 23 post-AI utilizing pregnancy-specific
      protein B (PSPB) in novel within-cow comparisons. Cows with single ovulations
      assigned to the L/L treatment had greater pre-ovulatory follicle diameter
      compared with cows assigned to the L/H or H/L treatments. Cows with single
      ovulations had greater pre-ovulatory follicle diameter compared with cows with
      double ovulations. Low P4 in H/L, L/H, and L/L increased double ovulation rate
      compared with H/H. Cows with double ovulations had greater pregnancies per AI
      (P/AI) on d 23 post-AI compared with cows with single ovulations but had greater
      losses if ovulations were unilateral. Cows with low P4 during the entire period
      of the ovulatory follicle development also had greater P/AI on d 23 post-AI
      compared with cows with high P4 during both phases. However, full-term P/AI was
      not different between treatments. This was a result of the greater incidence of
      pregnancy losses between d 35 and 56 of gestation for cows with unilateral double
      ovulations compared with bilateral double ovulations and single ovulatory cows.
      Cows with single ovulation and low circulating P4 during the dominance period of
      follicle development had increased pregnancy losses between d 35 and 56 of
      gestation compared with cows with single ovulations and high P4. The PSPB
      measurements on d 16 and 23 post-AI were highly accurate in the prediction of
      pregnancy at d 28. The PSPB differed on d 23 and 28 between cows that had versus
      cows that did not have pregnancy losses between d 28 and 35 of gestation. In
      summary, circulating concentrations of P4 during ovulatory follicle development
      affected numbers of follicles ovulated and timing of subsequent pregnancy losses.

PMID- 30197146
TI  - Interactions between whey protein or polymerized whey protein and soybean
      lecithin in model system.
AB  - Soybean lecithin is often used as a surfactant in food formulation. The aim of
      this study was to investigate the interactions between soybean lecithin (SL, 0
      3%, wt/vol) and whey protein (WP, 10%, wt/vol) or polymerized whey protein (PWP,
      10%, wt/vol) induced by heating WP solutions at 85 degrees C for 0 to 20 min at
      pH 7.0. The samples were evaluated for zeta potential, particle size, morphology,
      rheological properties, thermal properties, secondary structure, and surface
      hydrophobicity. Zeta potential of WP increased linearly as SL level increased
      from 0 to 3%, whereas that of PWP changed with plateau at SL level of 1%, which
      may be due to the aggregation of SL. The addition of SL increased the particle
      size and apparent viscosity of both WP and PWP. All the samples exhibited
      different morphology depending on SL level and heating time according to
      transmission electron microscopy images. Whey protein showed obviously decreased
      gelation time and increased storage modulus in the presence of SL. Differential
      scanning calorimetry curves confirmed the effects of SL on the thermal properties
      of both WP and PWP. Circular dichroism spectra indicated that SL had effects on
      the secondary structure of both WP and PWP. The changes in surface hydrophobicity
      indicated the hydrophobic interactions between WP/PWP and SL. Data indicate that
      the physicochemical and functional properties of WP and PWP can be altered by
      adding soybean lecithin.

PMID- 30197147
TI  - Effects of altering the ratio of dietary n-6 to n-3 fatty acids on spontaneous
      luteolysis in lactating dairy cows.
AB  - Objectives were to evaluate the effects of altering the dietary ratio of omega-6
      (n-6) to omega-3 (n-3) fatty acids on the profile of fatty acids and expression
      of genes related to the prostaglandin biosynthesis on endometrial tissue, uterine
      secretion of PGF2alpha, and timing of spontaneous luteolysis in dairy cows.
      Multiparous lactating Holstein cows (n = 45) were blocked based on milk yield
      and, within each block, assigned randomly to 1 of 3 dietary treatments at 14 d
      postpartum for 90 d. Diets were supplemented with a mixture of Ca salts of fish,
      safflower, and palm oils to create 3 different ratios of n-6 to n-3 fatty acids,
      namely R4, R5, and R6, which resulted in 3.9, 4.9, and 5.9 parts of n-6 to 1 part
      of n-3 fatty acids, respectively. Blood was sampled every 2 h from d 16 to 23 of
      the estrous cycle and assayed for concentrations of progesterone and the
      PGF2alpha metabolite 13,14-dihydro-15-keto-PGF2alpha (PGFM). In a subsequent
      estrous cycle, endometrial tissue was collected for biopsy on d 8 and endometrial
      fatty acids profile and gene expression were quantified. The proportion of
      arachidonic acid of the endometrial fatty acids increased as the dietary ratio n
      6 to n-3 fatty acids increased (R4 = 9.05, R5 = 11.64, and R6 = 13.41%). On the
      other hand, proportions of eicosapentaenoic (R4 = 2.85, R5 = 2.14, and R6 =
      2.02%) and docosahexaenoic (R4 = 3.30, R5 = 1.57, and R6 = 1.08%) decreased as
      the ratio of n-6 to n-3 fatty acids in the diet increased. Increasing the ratio
      of dietary n-6 to n-3 fatty acids increased mRNA expression of estrogen receptor
      1, oxytocin receptor, cyclooxygenase 2, prostaglandin E and F synthases, and
      steroidogenic acute regulatory protein in endometrium, but decreased expression
      of peroxisome proliferator-activated receptor gamma and insulin-like growth
      factor-1. The changes in endometrium gene expression caused by dietary treatments
      were associated with changes in the ratio of n-6 to n-3 fatty acids in the
      endometrium. As the ratio increased from R4 to R6, the number of PGFM pulses (R4
      = 5.6, R5 = 4.3, and R6 = 3.8 +/- 0.6 pulses; least squares means +/- standard
      error of the means) decreased, but the amplitude of the greatest PGFM pulse
      increased (R4 = 226, R5 = 267, and R6 = 369 +/- 38 pg/mL). Luteolysis by d 23 of
      the estrous cycle was observed in 79.6% of the cows (R4 = 11/14; R5 = 13/15; and
      R6 = 11/15) and day of spontaneous luteolysis did not differ among treatments (R4
      = 20.8; R5 = 21.1; and R6 = 21.0 +/- 0.4). Three pulses of PGFM was the best
      predictor of luteolysis in dairy cows. Collectively, supplying the same quantity
      of fatty acids in the diet of lactating dairy cows, but altering the ratio of n-6
      to n-3 fatty acids, influenced the endometrial fatty acids profile and gene
      expression and altered the pattern of prostaglandin synthesis; however, the
      changes were not sufficient to alter the length of the estrous cycle.

PMID- 30197148
TI  - Efficacy of vaccination with a Klebsiella pneumoniae siderophore receptor protein
      vaccine for reduction of Klebsiella mastitis in lactating cattle.
AB  - Clinical mastitis caused by Klebsiella spp. is an emerging problem in the US
      dairy industry and results in a high degree of financial losses to dairy workers.
      This study was conducted as a randomized, blinded, and placebo-controlled
      efficacy study of a Klebsiella pneumoniae siderophore receptor protein (SRP)
      vaccine (Kleb-SRP), with a total of 569 cows and heifers enrolled. The study was
      designed to look at vaccine effect on Klebsiella mastitis; however, the SRP in
      Klebsiella are highly conserved across coliform bacteria, which means that the
      vaccine has potential for cross-protection against all coliforms. Cows were
      paired based on parity, days in milk at enrollment, and somatic cell count.
      Within pairs, individuals were randomized to receive either Kleb-SRP or a placebo
      formulation. Following vaccination, the incidence of Klebsiella spp. and total
      coliform mastitis from natural exposure were compared to determine the efficacy
      of the vaccine. When analyzing all cows, the reduction of mastitis risk was not
      significant, though milk production increased 0.31 kg/d and somatic cell counts
      were reduced by 20.1%. When administered before calving, the vaccine reduced the
      risk of Klebsiella and total coliform mastitis by 76.9 and 47.5% respectively;
      however, we observed no significant effect when administered after calving. The
      vaccine, when administered before calving, also increased milk production by an
      average of 1.74 kg/d and reduced somatic cell counts by 64.8%. When administered
      after calving, we noted a slight decrease in daily milk production (0.39 kg) but
      no significant effect on somatic cell counts. All cows in the study (including
      vaccinates and placebo) received multiple doses of a commercially available
      licensed Escherichia coli bacterin. It should be noted that this herd was chosen
      because of the high number of clinical Klebsiella clinical mastitis cases this
      herd experienced before the trial and the extreme environmental challenge that
      was present from bedding with dried manure solids. The data from this study
      demonstrate efficacy of the Kleb-SRP vaccine against Klebsiella mastitis alone
      and coliform mastitis in general (including all coliforms) when administered
      before the initiation of a lactation cycle.

PMID- 30197149
TI  - Fetal metacarpal/metatarsal bone thickness as possible predictor of dystocia in
      Holstein cows.
AB  - Dystocia and perinatal calf mortality cause significant economic losses in the
      dairy cattle industry. Despite advanced ultrasound examination procedures, there
      is no reliable method to estimate the birth weight of calves in order to predict,
      prepartum, the risk of dystocia. The aim of this study was to predict calf birth
      weight and dystocia based on transrectal ultrasonographic (TRUS) examinations in
      late-term Holstein heifers and cows. Therefore, TRUS examination was performed on
      128 animals that were between 265 and 282 d of gestation to measure the bone
      thickness of the fetal metacarpus (MC) or metatarsus (MT). Fetal TRUS
      measurements were successful in 104 cases. Excluding twin deliveries, 97 fetal
      MC/MT bone thicknesses were measured and the mean (+/-SD) MC/MT thickness was
      2.54 +/- 0.37 cm. A novel index, the metacarpal/metatarsal index [MCTI = maternal
      body weight (kg)/fetal MC or MT thickness (cm)], was also calculated to study its
      association with calving ease. The average MCTI was 257.3 kg/cm in the studied
      population. A lower MCTI was associated with the risk of dystocia with an odds
      ratio of 2.074 that was not significantly different from 1 (95% confidence
      interval: 0.002-11.104). Fetal presentation, fetal age, fetal sex, body condition
      score of the dam, age of dam, and intercoxal and interischiadic distances were
      not related to dystocia. A fair phenotypic correlation (0.226) was found between
      MC/MT thickness and calf birth weight. The genetic correlation between MC/MT
      thickness and calf birth weight was 0.235. Our results indicate that late-term
      measurement of the fetal MC/MT bone thickness by means of TRUS examination
      augmented with the MCTI may have clinical significance in the prediction of
      dystocia in Holstein cattle. Because the odds ratio for dystocia based on MCTI
      determination was not significant, the applied technique should be improved based
      on further studies on prepartum TRUS examinations combined with dam pelvic
      measurements.

PMID- 30197150
TI  - Keto acid decarboxylase and keto acid dehydrogenase activity detected during the
      biosynthesis of flavor compound 3-methylbutanal by the nondairy adjunct culture
      Lactococcus lactis ssp. lactis F9.
AB  - 3-Methylbutanal is one of the primary substances that contribute to the nutty
      flavor in cheese. Lactococcus strains have been shown to have higher
      aminotransferase and alpha-keto acid decarboxylase activities compared with other
      microbes, indicating that they might form a higher amount of 3-methylbutanal by
      decarboxylation. Several dairy lactococcal strains have been successfully applied
      as adjunct cultures to increase the 3-methylbutanal content of cheese. Moreover,
      compared with dairy cultures, the nondairy lactococci are generally metabolically
      more diverse with more active AA-converting enzymes. Therefore, it might be
      appropriate to use nondairy lactococcal strains as adjunct cultures to enrich the
      3-methylbutanal content of cheese. This study thereby aimed to select a nondairy
      Lactococcus strain that is highly productive of 3-methylbutanal, identify its
      biosynthetic pathway, and apply it to cheese manufacture. Twenty wild nondairy
      lactococci isolated from 5 kinds of Chinese traditional fermented products were
      identified using 16S rRNA sequence analysis and were found to belong to
      Lactococcus lactis ssp. lactis. The nondairy strains were then screened in vitro
      for their production of 3-methylbutanal and whether they met the criteria to
      become an adjunct culture for cheese. The L. lactis ssp. lactis F9, isolated from
      sour bamboo shoot, was selected because of its higher 3-methylbutanal production,
      suitable autolysis rate, and lower acid production. The enzymes involved in the
      catabolic pathway of leucine were then evaluated. Both alpha-keto acid
      decarboxylase (6.96 MUmol/g per minute) and alpha-keto acid dehydrogenase (30.06
      MUmol/g per minute) activities were detected in nondairy L. lactis F9. Cheddar
      cheeses made with different F9 levels were ripened at 13 degrees C and analyzed
      after 90 d by a combination of instrumental and sensory methods. The results
      showed that adding nondairy L. lactis F9 significantly increased 3-methylbutanal
      content and enhanced the nutty flavor of the cheese without impairing its
      textural properties. Thus, nondairy L. lactis F9 efficiently enhanced the
      biosynthesis of 3-methylbutanal in vitro and in manufactured cheese.

PMID- 30197151
TI  - Quantified in vitro tibiofemoral contact during bodyweight back squats.
AB  - Squats are a common lower extremity task used in strength and conditioning,
      balance training, and rehabilitation. It is important to understand how slight
      alterations in lower extremity kinematics during a squat affect the internal
      joint loading of the knee. This study directly quantified tibiofemoral contact
      throughout the in vitro simulation of a bodyweight back squat performed two ways:
      a heel squat (knees in line with toes) and a toe squat (knees anterior to the
      toes) at peak knee flexion. Three cadaveric right lower extremities were
      instrumented and positioned into the University of Texas Joint Load Simulator.
      Kinematics, kinetics, and predicted muscle forces from a 20-year-old athletic
      male performing the two back squats were used as inputs for the in vitro
      simulations. The quantified tibiofemoral contact area, peak pressure, net force,
      and center of pressure location were significantly different between squat types
      (p > 0.05). Net contact area on the tibial plateau at peak knee flexion was
      significantly larger in the heel versus toe squat (599 +/- 80 mm2 vs. 469 +/- 125
      mm2; p < 0.05). Peak lateral pressure was significantly higher in the heel versus
      toe squat (2.73 +/- 0.54 MPa vs. 0.87 +/- 0.56 MPa; p < 0.05). Results suggest
      the heel squat generates an even load distribution, which is less likely to
      affect joint degeneration. Future in vitro simulations should quantify the
      effects lower extremity kinematics, kinetics, and individual muscle forces have
      on tibiofemoral contact parameters during common athletic tasks.

PMID- 30197152
TI  - Interdisciplinary training for cancer specialists: The time has come.

PMID- 30197154
TI  - Editorial Overview: Membranes and organelles: rethinking membrane structure,
      function and compartments.

PMID- 30197153
TI  - Ketamine for Rapid Sedation of Agitated Patients in the Prehospital and Emergency
      Department Settings: A Systematic Review and Proportional Meta-Analysis.
AB  - BACKGROUND: Rapid tranquilization of agitated patients can prevent injuries and
      expedite care. Whereas antipsychotics and benzodiazepines are commonly used for
      this purpose, ketamine has been suggested as an alternative. OBJECTIVE: The aim
      of this systematic review is to determine the safety and effectiveness of
      ketamine to sedate prehospital and emergency department (ED) patients with
      undifferentiated agitation. METHODS: Studies and case series of patients
      receiving ketamine for agitation were included. Studies were excluded if ketamine
      was used for analgesia, procedural sedation, asthma, or induction. Information
      sources included traditional and gray literature. RESULTS: The initial search
      yielded 1176 results from 14 databases. After review of titles and abstracts, 32
      studies were reviewed and 18 were included in the analysis, representing 650
      patient encounters. The mean dose of ketamine was 315 mg (SD 52) given
      intramuscularly, with adequate sedation achieved in 7.2 min (SD 6.2, range 2
      500). Intubation occurred in 30.5% of patients (95% confidence interval [CI] 27.0
      34.1%). In the majority of those patients, ketamine was administered by
      paramedics during ground transport and the patient was intubated on ED arrival.
      When ketamine was administered in the ED, the intubation rate was 1.8% (95% CI
      0.0-4.4%); in air medical transport, the rate was 4.9% (95% CI 0.0-10.3%). Other
      reported side effects included: vomiting, 5.2% (2.3-8.1%); hypertension, 12.1%
      (5.7-18.6%); emergence reactions, 3.5% (1.4-5.6%); transient hypoxia, 1.8% (0.1
      3.6%) and laryngospasm, 1.3% (0.3-2.3%). CONCLUSIONS: Ketamine provides rapid
      sedation for undifferentiated agitated patients and is associated with higher
      intubation rates when used by ground Emergency Medical Services paramedics,
      compared with ED or air medical transport patients. Other side effects are common
      but usually self-limiting.

PMID- 30197155
TI  - Nutritional Modulation of Innate Immunity: The Fat-Bile-Gut Connection.
AB  - Altered nutritional behavior in Western societies has unleashed numerous
      metabolic disorders, intimately linked to profound disruptions of the immune
      system. Here we summarize how nutrition modulates innate immunity. We outline
      recent findings regarding nutrient signaling and we particularly focus on the
      collateral impact of nutrition on the microbiome and on the bile acid (BA) pool.
      We discuss how the integration of postprandial signals by the gut microbiota,
      along with the absorption routes of metabolites, differentially affects immune
      niches to orchestrate immune responses. Finally, we discuss the potential
      consequences of these signals in the light of trained immunity. A better
      understanding of nutrition signaling will permit the optimization of therapeutic
      and dietary strategies against the arising immune disorders.

PMID- 30197156
TI  - Correlation between vestibular neuritis and cerebrovascular risk factors.
AB  - PURPOSE: To investigate the relationship between cerebrovascular risk factors,
      including carotid plaques, and vestibular neuritis (VN). MATERIALS AND METHODS:
      According to the inclusion and exclusion criteria, this retrospective study
      included 90 VN patients and 74 age- and sex-matched healthy controls from January
      2016 to December 2017. All subjects' records of cerebrovascular risk factors,
      such as age, sex, height, weight, history of hypertension and diabetes mellitus,
      living habits, serum levels of glucose, lipids, glycosylated haemoglobin (HbA1c),
      creatinine (CR), albumin (ALB), haemoglobin (HGB); and results of carotid colour
      Doppler ultrasound, were obtained and compared. RESULTS: No significant
      differences in age; sex ratio; body mass index; history of hypertension or
      diabetes mellitus; or mean serum lipids, glucose, creatinine, haemoglobin or
      HbA1c were found between patients with VN and healthy controls (all P > 0.05).
      The mean serum ALB level was significantly lower in VN patients than in healthy
      controls (40.65 +/- 3.77 vs 42.84 +/- 4.32, P = 0.001).The prevalence of carotid
      plaques was significantly higher in VN patients than in healthy controls (36.67%
      vs. 16.22%, P = 0.003). Regression analyses demonstrated that a high frequency of
      carotid plaques was associated with VN with an odds ratio of 2.252 (95% CI 1.165
      5.458, P = 0.019). CONCLUSION: A high frequency of carotid plaques may be a risk
      factor for VN.

PMID- 30197157
TI  - Prediction of permanent hypoparathyroidism by parathyroid hormone and serum
      calcium 24 h after thyroidectomy.
AB  - PURPOSE: To assess the value of 24-hour intact parathyroid hormone (iPTH), serum
      calcium, and decreases in both were evaluated against preoperative values (iPTH
      and serum calcium decline) and used to determine the existence of permanent
      hypoparathyroidism (pHPP) after total thyroidectomy (TT). MATERIALS AND METHODS:
      The clinical data of patients who underwent total thyroidectomy in our hospital
      between September 2014 and July 2015 were retrospectively analyzed. RESULTS:
      There were 42 cases with normal parathyroid function, 58 cases with temporary
      HPP, and 10 cases with pHPP. When iPTH and serum calcium were administered at 24
      h after surgery, iPTH decline and calcium decline differed significantly among
      the three groups above (P < .01). The accuracy and positive predictive value of
      24 h iPTH for pHPP were higher than any one of the others. The sensitivity,
      specificity, false positive rate, and accuracy were 100%, 95%, 33.33%, and
      94.45%, respectively. The AUC was 0.982 when 24-hour iPTH was equal to or <3.15
      pg/mL. The use of blood calcium equal to or <2.03 mmol/L (8.12 mg/dL) pointed to
      a diagnosis of pHPP, with a sensitivity of 100%, specificity of 63%, false
      positive rate of 78.72%, and accuracy of 66.36%. CONCLUSIONS: Measurement of the
      postoperative 24-h intact parathyroid hormone and serum calcium concentration can
      predict the occurrence of permanent hypoparathyroidism and the former is more
      advantageous. Postoperative 24-h intact parathyroid hormone equal to or <3.15
      pg/mL is a reliable index, and it is suitable for the prediction of postoperative
      permanent hypoparathyroidism.

PMID- 30197158
TI  - Metformin prescription status and abdominal aortic aneurysm disease progression
      in the U.S. veteran population.
AB  - BACKGROUND: Identification of a safe and effective medical therapy for abdominal
      aortic aneurysm (AAA) disease remains a significant unmet medical need. Recent
      small cohort studies indicate that metformin, the world's most commonly
      prescribed oral hypoglycemic agent, may limit AAA enlargement. We sought to
      validate these preliminary observations in a larger cohort. METHODS: All patients
      with asymptomatic AAA disease managed in the Veterans Affairs Health Care System
      between 2003 and 2013 were identified by International Classification of
      Diseases, Ninth Revision codes. Those with a concomitant diagnosis of diabetes
      mellitus who also received two or more abdominal imaging studies (computed
      tomography, magnetic resonance imaging, or ultrasound) documenting the presence
      and size of an AAA, separated by at least 1 year, were included for review.
      Maximal AAA diameters were determined from radiologic reports. Further data
      acquisition was censored after surgical AAA repair, when performed.
      Comorbidities, active smoking status, and outpatient medication records (within 6
      months of AAA diagnosis) were also queried. Yearly AAA enlargement rates, as a
      function of metformin treatment status, were compared using two statistical
      models expressed in millimeters per year: a multivariate linear regression (model
      1) and a multivariate mixed-effects model with random intercept and random slope
      (model 2). RESULTS: A total of 13,834 patients with 58,833 radiographic records
      were included in the analysis, with radiology imaging follow-up of 4.2 +/- 2.6
      years (mean +/- standard deviation). The average age of the patients at AAA
      diagnosis was 69.8 +/- 7.8 years, and 39.7% had a metformin prescription within
      +/-6 months of AAA. The mean growth rate for AAAs in the entire cohort was 1.4 +/
      2.0 mm/y by model 1 analysis and 1.3 +/- 1.6 mm/y by model 2 analysis. The
      unadjusted mean rate of AAA growth was 1.2 +/- 1.9 mm/y for patients prescribed
      metformin compared with 1.5 +/- 2.2 mm/y for those without (P < .001), a 20%
      decrease. This effect remained significant when adjusted for variables relevant
      on AAA progression: metformin prescription was associated with a reduction in
      yearly AAA growth rate of -0.23 mm (95% confidence interval, -0.35 to -0.16; P <
      .001) by model 1 analysis and 0.20 mm/y (95% confidence interval, -0.26 to -0.14;
      P < .001) by model 2 analysis. A subset analysis of 7462 patients with baseline
      AAA size of 35 to 49 mm showed a similar inhibitory effect (1.4 +/- 2.0 mm/y to
      1.7 +/- 2.2 mm/y; P < .001). Patients' factors associated with an increased
      yearly AAA growth rate were baseline AAA size, metastatic solid tumors, active
      smoking, chronic obstructive pulmonary disease, and chronic renal disease.
      Factors associated with decreased yearly AAA growth rates included prescriptions
      for angiotensin II type 1 receptor blockers or sulfonylureas and the presence of
      diabetes-related complications. CONCLUSIONS: In a nationwide analysis of diabetic
      Veterans Affairs patients, prescription for metformin was associated with
      decreased AAA enlargement. These findings provide further support for the conduct
      of prospective clinical trials to test the ability of metformin to limit
      progression of early AAA disease.

PMID- 30197159
TI  - Variability in hospital costs for carotid artery revascularization.
AB  - OBJECTIVE: The objective of this study was to understand drivers of cost for
      carotid endarterectomy (CEA) and carotid artery stenting (CAS) and to compare
      variation in cost among cases performed by vascular surgery (VS) with other
      services (OSs). METHODS: We collected internal hospital claims data for CEA and
      CAS between September 2013 and August 2015 and performed a financial analysis of
      all hospital costs including room accommodations, medications, medical and
      surgical supplies, imaging, and laboratory tests. Cases were stratified by
      presence of symptoms and procedure type, and costs of procedures performed by VS
      were compared with those performed by OSs. RESULTS: The cohort comprised 144
      patients (78 asymptomatic, 66 symptomatic; 44 CAS, 100 CEA) receiving unilateral
      revascularization. VS (24 CAS, 70 CEA) and neurosurgery and neurointerventional
      radiology services (20 CAS, 30 CEA) performed all procedures. Age (71 +/- 9 years
      vs 70 +/- 11 years; P = .8) and length of stay (1.7 +/- 2.1 days vs 2.2 +/- 2.4
      days; P = .73) were similar for VS and OSs. Symptoms were present before
      revascularization for 46% and were more commonly treated by OSs (78% vs 29%; P <
      .001). Case mix index was similar after stratifying by symptoms (asymptomatic,
      1.28 +/- 0.35 vs 1.39 +/- 0.42 [P = .5]; symptomatic, 1.66 +/- 0.73 vs 1.82 +/-
      0.81 [P = .9]). The largest cost components were operating room (OR)-related
      costs, beds, and supplies, together accounting for 76% of costs. Asymptomatic
      patients had 37% lower average hospital costs. For asymptomatic CAS, average
      index hospitalization cost was 17% less for VS compared with OSs because of 78%
      lower intensive care unit costs, 44% lower OR-related costs, 40% lower medication
      costs, and 24% lower cardiac testing costs. VS had 22% higher supply costs. For
      asymptomatic CEA, average index hospitalization costs were 22% lower for VS,
      driven by lower OR-related costs (28%), medications (28%), imaging (62%), and
      neurointerventional monitoring (64%). Costs were 38% higher for CAS vs CEA. For
      symptomatic CAS, costs were similar for both groups. For symptomatic CEA, total
      costs were 14% lower for VS compared with OSs, driven by 25% lower OR-related
      costs, 62% lower neurointerventional monitoring, 20% step-down beds, and 28%
      lower supply costs (and counterbalanced by 117% higher intensive care unit
      costs). CONCLUSIONS: VS average hospital costs were lower for asymptomatic CAS
      and all CEAs compared with OSs. Drivers of higher cost appear to be attributed to
      variation in physicians' practice as well as patients' complexity, affording an
      opportunity to reduce cost by establishing standard practices when appropriate.

PMID- 30197160
TI  - What is ventricular fibrillation undersensing?
AB  - Ventricular fibrillation (VF), uninterrupted, is fatal within minutes.
      Implantable cardioverter defibrillators (ICDs) sense ventricular electrograms
      (EGMs) during VF and detect the VF rhythm (a sequence of VF sensed events) to
      deliver a shock to terminate VF and save lives. VF sensing and detection in
      Medtronic ICDs has been reported to be highly sensitive. However, Castellano et
      al. reported that Medtronic ICDs have the potential for high levels of
      undersensing in VF, sufficient to underdetect VF and withhold life-saving
      therapy. This manuscript reviews the process of EGM sensing and VF detection in
      ICDs and compares the process of sensing in Medtronic ICDs with the process
      described in this recent publication.

PMID- 30197162
TI  - The suitability of a DRG casemix system in the Maltese hospital setting.
AB  - The healthcare system in Malta is financed through global budgets and healthcare
      is provided free at the point of use. This paper is a first attempt to examine
      the feasibility of introducing a Diagnosis Related Groups casemix system for
      Malta, not necessarily for payment and funding purposes, but as a tool to help
      describe, manage and measure resource use. This is particularly challenging in
      view of the constraints and characteristics of a small state country. The study
      evaluates the applicability of the MS-DRG (Version 27.0) Grouper to describe
      acute hospital activity on the island. The classification of 151,615 admissions
      between 2009-2011 resulted in 636 DRG categories. Around half of these DRGs
      accounted for 99% of the total activity at the hospital, while 296 DRG categories
      had fewer than 15 cases over the period. Patient length of stay is used to
      explain resource use and the Coefficient of Multiple Determination obtained was
      of 0.19 (improving to 0.25 when a number of trimming algorithms were applied). A
      good proportion of the resulting DRGs had a Coefficient of Variation, which
      indicates a low degree of variability within the obtained DRG groups. This
      presents good evidence to support the introduction of a DRG system in Malta
      particularly in view of the recent drive towards more public-private partnerships
      and legislation on cross-border patient treatment.

PMID- 30197161
TI  - Glycemic reduction alters white blood cell counts and inflammatory gene
      expression in diabetes.
AB  - OBJECTIVE: Systemic inflammation contributes to cardiovascular disease in
      patients with type 2 diabetes, and elevated white blood cell (WBC) counts are an
      established risk factor. Our goal is to describe changes in WBCs and inflammatory
      markers after glycemic reductions in diabetes. RESEARCH DESIGN AND METHODS: This
      study enrolled 63 subjects with poorly controlled diabetes, defined as hemoglobin
      A1c (HbA1c) >=8% [64 mmol/mol]. Circulating granulocytes and mononuclear cells
      were separated by histopaque double-density protocol. Inflammatory markers from
      these isolated WBCs were assessed at baseline and after 3 months of medical
      management. RESULTS: After 3 months, significant glycemic reduction, defined as a
      decrease in HbA1c >= 1.5%, occurred in 42 subjects. Fasting plasma glucose
      decreased by 47% (165.6 mg/dL), and HbA1c decreased from 10.2 +/- 1.8 to 6.8 +/-
      0.9. Glycemic reductions were associated with a 9.4% decrease in total WBC
      counts, 10.96% decrease in neutrophils, and 21.74% decrease in monocytes. The
      mRNA levels of inflammatory markers from granulocytes and mononuclear cells
      decreased, including receptor for advanced glycation endproducts; S100 calcium
      binding proteins A8, A9, A12; kruppel-like factor 5; and IL-1. Also, circulating
      levels of IL-1beta and C-reactive protein decreased. Insulin dose was a mediator
      between HbA1c and both total WBC and neutrophil counts, but not changes in WBC
      inflammatory markers. In contrast, the 17 subjects without significant glycemic
      reductions showed no significant differences in their WBC counts and proteins of
      inflammatory genes. CONCLUSION: Significant glycemic reduction in subjects with
      poorly controlled diabetes led to reduced circulating WBC counts and inflammatory
      gene expression.

PMID- 30197163
TI  - The microbiology of infected pancreatic necrosis.
AB  - BACKGROUND: Acute pancreatitis (AP) continues to cause significant morbidity and
      mortality, especially when it leads to infected pancreatic necrosis (IPN). Modern
      treatment of IPN frequently involves prolonged courses of antibiotics in
      combination with minimally invasive therapies. This study aimed to update the
      existing evidence base by identifying the pathogens causing IPN and therefore aid
      future selection of empirical antibiotics. METHODS: Clinical data, including
      microbiology results, of consecutive patients with IPN undergoing minimally
      invasive necrosectomy at our institution between January 2009 and July 2016 were
      retrospectively reviewed. RESULTS: The results of 40 patients (22 males and 18
      females, median age 60 years) with IPN were reviewed. The etiology of AP was
      gallstones, alcohol, dyslipidemia and unknown in 31, 2, 2 and 5 patients,
      respectively. The most frequently identified microbes in microbiology cultures
      were Enterococcus faecalis and faecium (22.5% and 20.0%) and Escherichia coli
      (20.0%). In 19 cases the cultures grew multiple organisms. The antibiotics with
      the least resistance amongst the microbiota were teicoplanin (5.0%), linezolid
      (5.6%), ertapenem (6.5%), and meropenem (7.4%). CONCLUSION: The carbapenem
      antibiotics, ertapenem and meropenem provide good antimicrobial cover against the
      common, mainly enteral, microorganisms causing IPN. Culture and sensitivity
      results of acquired samples should be regularly reviewed to adjust prescribing
      and monitor for emergence of resistance.

PMID- 30197164
TI  - Comparison of laparoscopic proximal gastrectomy with double-tract reconstruction
      and laparoscopic total gastrectomy in terms of nutritional status or quality of
      life in early gastric cancer patients.
AB  - BACKGROUND: This study aimed to evaluate the surgical outcomes of laparoscopic
      proximal gastrectomy (LPG) reconstructed by the double-tract method in comparison
      to those of laparoscopic total gastrectomy (LTG). METHODS: A retrospective review
      of the prospectively established database identified early gastric cancer
      patients who underwent LPG (n = 34) or LTG (n = 46) between January 2011 and
      December 2015. Baseline characteristics and surgical outcomes including
      postoperative complications, changes in body composition, nutritional status, and
      quality of life (QOL) after surgery were compared between the LPG and LTG
      patients. RESULTS: Operating time was significantly longer in the LTG group
      (240.7 +/- 43.9 vs. 211.7 +/- 32.8 min, p = 0.007). The incidence of grade II or
      more complications and the hospital stay were comparable between the groups.
      There was no significant difference between the groups in terms of body
      composition using a bioelectrical impedance method in 1 year postoperatively.
      Nutritional status assessed by serum hemoglobin, iron, vitamin B12, albumin,
      total protein, and total cholesterol levels and postoperative changes in quality
      of life up to 2 years after surgery were also similar between the groups. Vitamin
      B12 supplementation was required in 75.4% of the patients in the LTG group and
      46.5% in the LPG group within 2 years after surgery (p = 0.005). CONCLUSION: LPG
      with double-tract reconstruction appears superior in preventing vitamin B12
      deficiency compared to LTG, particularly after 1 year after the surgery, although
      it offered little benefit in terms of postoperative body composition changes and
      QOL.

PMID- 30197165
TI  - A long-term conditional survival analysis for gastric cancer based on 7th and 8th
      TNM classification in Eastern and Western populations.
AB  - BACKGROUND: To compare the power to predict the 5-year conditional disease
      specific survival (CS5) between the 7th and 8th editions of the TNM for gastric
      cancer (GC) patients. METHOD: This retrospective study recruited 20,548 patients
      who underwent GC surgery from the databases of the Surveillance, Epidemiology,
      End Results and a center in Asia. The CS5 was evaluated with the 7th and 8th TNM
      classification. RESULTS: A two-step model showed that at the 3-5th postoperative
      years, the 8th staging remained an independent risk factor, whereas there was no
      significant difference for 7th -edition staging. Further analysis of the ability
      to predict CS5 indicated that there were significant differences in the CS5 of
      7th -edition stages IIb and IIIa at baseline and at the postoperative 1-4th years
      (all p < 0.05, Cohen's d > 0.5). However, the CS5 of the fifth year was similar
      between them (p = 0.307, Cohen's d = 0.35). Meanwhile, the results indicated that
      the 8th -edition staging could effectively determine the CS5 among stages Ia, Ib,
      IIa, IIb, IIIa, and IIIb at baseline and at the postoperative 1-5th years (all p
      < 0.05). However, neither the 7th - nor the 8th -edition staging could predict
      the CS5 for stages IIIb and IIIc from the postoperative third to fifth years (all
      p > 0.05). CONCLUSIONS: For patients with stages IIB and IIIA GC, the 8th TNM has
      a higher discriminatory value than the 7th edition for CS5 after the
      postoperative fourth year. However, a more detailed classification system is
      still needed to predict conditional survival for GC.

PMID- 30197166
TI  - Interimplant femoral fractures: risk factors, treatment and evolution.
AB  - OBJECTIVE: The aim of this study is to determine the risk factors involved in the
      development of these fractures and analyze the treatments used as well as their
      influence on the clinical and functional prognosis of patients. MATERIALS AND
      METHODS: We made an observational, retrospective case-control study, with a
      sample of 38 patients (40 femoral bones) operated in our hospital, who had two
      femoral ipsilateral implants, proximal and distal. We found 10 cases of
      interimplant fracture and 28 patients who had not suffered a fracture (2 of them
      had bilateral implants). We analyzed the influence of different variables, such
      as age, gender, comorbidities, radiological variables, type of treatments
      employed, clinical evolution, etc. RESULTS: the female sex was predominant in
      both groups, 80.7 was the average age. Osteoporosis was statistically significant
      (P=.007) for the development of these fractures. We did not find statistical
      significance in the radiological variables. Surgical treatment was the most
      frequent, and the plate of osteosynthesis the most employed option. We found a
      death rate of 40% at 4 years. Although all fractures healed, the survivors'
      ambulation ability was reduced. CONCLUSIONS: interimplant fractures are
      predominant in elderly women. Osteoporosis is a statistically significant risk
      factor. Despite optimal treatment and fracture healing, functional outcomes were
      decreased. Specific classification systems and therapeutic algorithms are
      necessary to improve the management and prognosis of these patients.

PMID- 30197167
TI  - Intraplaque Microvascular Flow Signal in Superb Microvascular Imaging and
      Magnetic Resonance Imaging Carotid Plaque Imaging in Patients with Atheromatous
      Carotid Artery Stenosis.
AB  - Carotid artery atherosclerosis is one of the major risk factors for ischemic
      stroke. Intraplaque neovascularization (IPN) is one of the steps toward the
      development of vulnerable plaque. Superb microvascular imaging (SMI) is a new
      ultrasonographic technique for visualizing low-velocity and microvascular flow by
      clutter suppression to extract flow signals from large to small vessels and
      enables visualization of intraplaque microvascular flow (IMVF) without echo
      contrast media. We aimed to investigate the association between IMVF signal in
      SMI and MRI plaque imaging among patients with atherosclerotic carotid stenosis.
      We prospectively enrolled patients (>18 years old) with mild to severe carotid
      stenosis (more than 50% in cross-sectional area) diagnosed by carotid
      ultrasonography between August 2017 and April 2018, irrespective of sex and
      history of stroke. A total of 40 patients (31 men, 9 women; mean age, 75.1 +/-
      10.0 years) were enrolled. SMI revealed IPN findings in 21 patients. SMI clearly
      visualized the direction of pulsatile flow movement in microvessels and IPN was
      easily classified into the two types of Type V (n=2) and Type E (n=19).
      Multivariate logistic regression analysis presented that microvascular flow
      signal in carotid plaque on SMI was identified as a significant predictor of
      intraplaque hemorrhage as evaluated by MRI (OR, 8.46; 95%CI, 1.44-49.9; p=0.018).
      This study demonstrated a significant association between the presence of IMVF
      signal in SMI and intraplaque hemorrhage characterized by high-intensity lesions
      on MRI T1-FFE images.

PMID- 30197168
TI  - Association and Clinical Outcomes of Marijuana in Patients with Intracerebral
      Hemorrhage.
AB  - OBJECTIVE: An epidemiological relationship between intracerebral hemorrhage (ICH)
      and marijuana use is not known. Data about the impact of marijuana on ICH
      patient's outcomes remain scarce. METHODS: The Nationwide Inpatient Sample was
      investigated from 2004 to 2011 to identify cohorts with marijuana (N = 2,496,165)
      and nonmarijuana (N = 116,163,454) usage. Patients with a primary diagnosis of
      ICH were identified using International Classification of Diseases, Ninth
      Edition, Clinical Modification codes. Univariable analysis was used to compare
      demographics and risk factors for ICH, and to study patient outcomes in ICH
      patients with or without marijuana use. Binary logistic regression analyses were
      used to study marijuana as independent predictor of ICH and to assess its effect
      on patient outcomes. RESULTS: The prevalence of ICH was greater in the marijuana
      cohort (relative risk: 1.11, confidence interval [CI]: 1.07-1.16). However,
      marijuana use (odds ratio [OR]: 1.063; CI: .963-1.173) was not an independent
      predictor of ICH after adjusting for other illicit drug use and ICH risk factors.
      For in-hospital outcomes, marijuana users had fewer adverse discharge
      dispositions (OR .78; CI: .72-.86), reduced length of hospitalization (OR .54;
      CI: .48-.61), and lower hospitalization cost (OR .72; CI: .64-.81) but higher in
      hospital mortality (OR 1.26; CI: 1.12-1.41). CONCLUSIONS: Marijuana users are
      more likely to be admitted with ICH, however, marijuana is not an independent
      risk factor for ICH. Although marijuana has paradoxical effect on ICH related
      outcomes, higher mortality rates in marijuana users offset any potential
      protective effect among ICH patients.

PMID- 30197169
TI  - A Functional Polymorphism rs145204276 in the Promoter of Long Noncoding RNA GAS5
      Is Associated with an Increased Risk of Ischemic Stroke.
AB  - Long noncoding RNAs (lncRNAs) play crucial roles in the regulation of
      pathological process of ischemic stroke (IS) via affecting cell apoptosis,
      inflammation, cell death, and angiogenesis. LncRNA growth arrest-specific 5
      (GAS5) was observed to be up-regulated in IS, acting as a competing endogenous
      RNA for miR-137 to mediate the Notch1 signaling pathway. In this study, we aimed
      to whether an insertion/deletion polymorphism (rs145204276) in the promoter of
      GAS5 was related to the risk of IS. The rs145204276 was genotyped using
      polymerase chain reaction (PCR)-polyacrylamide gel electrophoresis in 509
      patients with IS and 668 healthy controls with frequencies matched to cases
      regarding age, gender, living area, and ethnicity. The GAS5 expression levels
      were determined using qPCR and relative luciferase activity was measured using
      the Dual Luciferase assay system. The presence of del/del genotype and del allele
      was associated with an increased risk of IS [del/del versus ins/ins: adjusted
      odds ratio (OR) = 2.06, 95% confidence interval (CI): 1.37-3.11; recessive model:
      adjusted OR = 2.07, 95% CI: 1.41-3.04; del versus ins: adjusted OR = 1.31, 95%
      CI: 1.08-1.57]. Results from logistic regression analysis identified risk factors
      for IS, including hypertension, total cholesterol, triglyceride, low-density
      lipoprotein cholesterol, and rs145204276 del/del genotype. Furthermore, patients
      carrying rs145204276 del/del genotype had significantly higher levels of GAS5 and
      cells transfected with rs145204276 del allele exhibited a larger increase in
      luciferase activity. These findings indicate that rs145204276 del allele
      exhibited a significant association with an increased IS susceptibility by
      elevating the transcriptional activity and subsequently enhancing the expression
      of lncRNA GAS5.

PMID- 30197170
TI  - Right Ventricular Failure After Left Ventricular Assist Device Placement-The
      Beginning of the End or Just Another Challenge?
AB  - Left ventricular assist device (LVAD) therapy has greatly improved outcomes in
      patients with end-stage heart failure. However, development of right ventricular
      failure (RVF) in LVAD recipients is associated with increased long- and short
      term morbidity and mortality. The incidence of RVF after LVAD placement is
      difficult to assess due to the lack of a common definition. Risk-score models
      attempting to identify patients at risk for RVF prior to the placement of LVADs
      had equivocal outcomes. With the exception of cardiac magnetic resonance, right
      ventricle (RV) imaging lacks accuracy. Echocardiographic evaluation is expanded
      to 3D technology and deformation imaging in an attempt to get further insight
      into the functional reserve of the RV in states of abnormal RV function. Beyond
      commonly use agents, pharmacological treatment for RVF and post-bypass vasoplegia
      in LVAD patients include the off-label use of methylene blue and/or
      hydroxycobalamin. Communication among the perioperative team may be beneficial
      for early initiation of temporary right-sided mechanical support in order to
      avoid RVF-related complications. As long-term RVADs are unavailable, currently
      approved treatment of prolonged RVF is limited to heart transplantation or the
      placement of a total artificial heart as bridge-to-transplant. Strategies to
      improve outcome in this patient population should include better risk
      stratification for RVF prior to LVAD placement as well as frank discussions about
      LVAD candidacy in patients ineligible for transplantation. The development of
      durable right-sided mechanical support would improve the scope of care of LVAD
      patients developing persistent RVF.

PMID- 30197172
TI  - CNS efficacy of osimertinib in EGFR-mutated advanced NSCLC.

PMID- 30197171
TI  - Maternal hormonal contraception and childhood leukaemia.

PMID- 30197173
TI  - Preliminary activity of capmatinib with gefitinib in NSCLC.

PMID- 30197174
TI  - Maternal use of hormonal contraception and risk of childhood leukaemia: a
      nationwide, population-based cohort study.
AB  - BACKGROUND: Maternal hormonal contraception has been suspected of being linked to
      an increased risk of childhood cancer. The aim of this study was to assess the
      association between maternal use of hormonal contraception and diagnosis of
      leukaemia in their children. METHODS: In this cohort study, we followed a
      nationwide cohort of 1 185 157 liveborn children between 1996 and 2014 listed in
      the Danish Medical Birth Registry and identified those diagnosed with leukaemia
      in the Danish Cancer Registry. Redeemed prescriptions from the Danish National
      Prescription Registry provided information about maternal hormonal contraceptive
      use, categorised as: no use (never used contraception before birth; reference
      category), previous use (>3 months before start of pregnancy), and recent use
      (<=3 months before and during pregnancy). We also calculated risk estimates
      separately for maternal hormonal contraceptive use during pregnancy. The primary
      outcome of interest was a diagnosis of any leukaemia in the children. Secondary
      outcomes were diagnoses of lymphoid leukaemia and non-lymphoid leukaemia. We used
      Cox proportional hazards models to estimate hazard ratios (HRs) with 95% CIs for
      risk of leukaemia in children. The Data Protection Agency registration number for
      this study is 2017-41-5221. FINDINGS: Between Jan 1, 1996, and Dec 31, 2014, the
      1 185 157 liveborn children accumulated 11 114 290 person-years of follow-up
      (median 9.3 years, IQR 4.6-14.2), during which 606 children were diagnosed with
      leukaemia (465 with lymphoid leukaemia and 141 with non-lymphoid leukaemia).
      Children born to women with recent use of any type of hormonal contraception were
      at higher risk for any leukaemia than children of women who never used
      contraception (HR 1.46, 95% CI 1.09-1.96; p=0.011); and for exposure during
      pregancy the risk was 1.78 (0.95-3.31; p=0.070). No association was found between
      timing of use and risk for lymphoid leukaemia (HR 1.23, 95% CI 0.97-1.57,
      p=0.089, for previous use and 1.27, 0.90-1.80, p=0.167, for recent use); however,
      the HRs for non-lymphoid leukaemia were 2.17 (1.22-3.87; p=0.008) for recent use
      and 3.87 (1.48-10.15; p=0.006) for use during pregnancy. Hormonal contraception
      use close to or during pregnancy might have resulted in one additional case of
      leukaemia per about 50 000 exposed children, or 25 cases during the 9-year study
      period. INTERPRETATION: Our findings suggest the maternal hormonal use affects
      non-lymphoid leukaemia development in children. Since almost no risk factors have
      been established for childhood leukaemia, these findings suggest an important
      direction for future research into its causes and prevention. FUNDING: The Danish
      Cancer Research Foundation, the Arvid Nilssons Foundation, the Gangsted
      Foundation, the Harboe Foundation, and the Johannes Clemmesens Foundation.

PMID- 30197176
TI  - Pancreatic mucinous cystadenoma doubly complicated by acute pancreatitis and
      retroperitoneal rupture.
AB  - Mucinous cystadenomas are the most frequent cystic benign tumors of the pancreas.
      They are characterized by a malignant potential. Acute pancreatitis is their most
      common complication. This manuscript reports a unique complication of mucinous
      cystadenomas of the pancreas: retroperitoneal rupture associated to acute
      pancreatitis. After resuscitation, the patient underwent surgery. A cystic mass
      of the pancreas tail with retroperitoneal rupture was found. Splenopancreatectomy
      was performed. Outcomes were straightforward. After 3 years of follow-up, no
      signs of recurrence are highlighted.

PMID- 30197175
TI  - Cancer-Associated PIK3CA Mutations in Overgrowth Disorders.
AB  - PIK3CA is one of the most commonly mutated genes in solid cancers. PIK3CA
      mutations are also found in benign overgrowth syndromes, collectively known as
      PIK3CA-related overgrowth spectrum (PROS). As in cancer, PIK3CA mutations in PROS
      arise postzygotically, but unlike in cancer, these mutations arise during
      embryonic development, with their timing and location critically influencing the
      resulting disease phenotype. Recent evidence indicates that phosphoinositide 3
      kinase (PI3K) pathway inhibitors undergoing trials in cancer can provide a
      therapy for PROS. Conversely, PROS highlights gaps in our understanding of PI3K's
      role during embryogenesis and in cancer development. Here, we summarize current
      knowledge of PROS, evaluate challenges and strategies for disease modeling, and
      consider the implications of PROS as a paradigm for understanding activating
      PIK3CA mutations in human development and cancer.

PMID- 30197177
TI  - Retraction notice to "Si RNA inhibition of GRP58 associated with decrease in
      mitomycin C-induced DNA cross-linking and cytotoxicity": [Chem. Biol. Interact.
      162/1 (2006) 81-87].
AB  - This article has been retracted: please see Elsevier Policy on Article Withdrawal
      (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This
      article has been retracted at the request of the Office of Integrity of the
      University of Maryland due to data entered in Fig 3 of the publication that were
      not supported by raw data, in addition to the fact that the statistical
      evaluations were adultered.

PMID- 30197178
TI  - Corrigendum to "Unplanned Intraoperative Extubations in Pediatric Neurosurgery:
      Analysis of Case Series to Increase Patient Safety" [World Neurosurgery 115
      (2018), e1-e6].

PMID- 30197179
TI  - Corrigendum to "How does maternal oxytocin influence children's mental health
      problem and maternal mental health problem? [Psychiatry Research 258C (2017) 124
      129].

PMID- 30197180
TI  - Computational Model of Chimeric Antigen Receptors Explains Site-Specific
      Phosphorylation Kinetics.
AB  - Chimeric antigen receptors (CARs) have recently been approved for the treatment
      of hematological malignancies, but our lack of understanding of the basic
      mechanisms that activate these proteins has made it difficult to optimize and
      control CAR-based therapies. In this study, we use phosphoproteomic mass
      spectrometry and mechanistic computational modeling to quantify the in vitro
      kinetics of individual tyrosine phosphorylation on a variety of CARs. We show
      that each of the 10 tyrosine sites on the CD28-CD3zeta CAR is phosphorylated by
      lymphocyte-specific protein-tyrosine kinase (LCK) with distinct kinetics. The
      addition of CD28 at the N-terminal of CD3zeta increases the overall rate of
      CD3zeta phosphorylation. Our computational model identifies that LCK
      phosphorylates CD3zeta through a mechanism of competitive inhibition. This model
      agrees with previously published data in the literature and predicts that
      phosphatases in this system interact with CD3zeta through a similar mechanism of
      competitive inhibition. This quantitative modeling framework can be used to
      better understand CAR signaling and T cell activation.

PMID- 30197182
TI  - Confidence Analysis of DEER Data and Its Structural Interpretation with Ensemble
      Biased Metadynamics.
AB  - Given its ability to measure multicomponent distance distributions between
      electron-spin probes, double electron-electron resonance (DEER) spectroscopy has
      become a leading technique to assess the structural dynamics of biomolecules.
      However, methodologies to evaluate the statistical error of these distributions
      are not standard, often hampering a rigorous interpretation of the experimental
      results. Distance distributions are often determined from the experimental DEER
      data through a mathematical method known as Tikhonov regularization, but this
      approach makes rigorous error estimates difficult. Here, we build upon an
      alternative, model-based approach in which the distance probability distribution
      is represented as a sum of Gaussian components, and use propagation of errors to
      calculate an associated confidence band. Our approach considers all sources of
      uncertainty, including the experimental noise, the uncertainty in the fitted
      background signal, and the limited time span of the data collection. The
      resulting confidence band reveals the most and least reliable features of the
      probability distribution, thereby informing the structural interpretation of DEER
      experiments. To facilitate this interpretation, we also generalize the molecular
      simulation method known as ensemble-biased metadynamics (EBMetaD). This method,
      originally designed to generate maximal-entropy structural ensembles consistent
      with one or more probability distributions, now also accounts for the uncertainty
      in those target distributions exactly as dictated by their confidence bands.
      After careful benchmarks, we demonstrate the proposed techniques using DEER
      results from spin-labeled T4 lysozyme.

PMID- 30197181
TI  - Human Dystrophin Structural Changes upon Binding to Anionic Membrane Lipids.
AB  - Scaffolding proteins play important roles in supporting the plasma membrane
      (sarcolemma) of muscle cells. Among them, dystrophin strengthens the sarcolemma
      through protein-lipid interactions, and its absence due to gene mutations leads
      to the severe Duchenne muscular dystrophy. Most of the dystrophin protein
      consists of a central domain made of 24 spectrin-like coiled-coil repeats (R).
      Using small angle neutron scattering (SANS) and the contrast variation technique,
      we specifically probed the structure of the three first consecutive repeats 1-3
      (R1-3), a part of dystrophin known to physiologically interact with membrane
      lipids. R1-3 free in solution was compared to its structure adopted in the
      presence of phospholipid-based bicelles. SANS data for the protein/lipid
      complexes were obtained with contrast-matched bicelles under various phospholipid
      compositions to probe the role of electrostatic interactions. When bound to
      anionic bicelles, large modifications of the protein three-dimensional structure
      were detected, as revealed by a significant increase of the protein gyration
      radius from 42 +/- 1 to 60 +/- 4 A. R1-3/anionic bicelle complexes were further
      analyzed by coarse-grained molecular dynamics simulations. From these studies, we
      report an all-atom model of R1-3 that highlights the opening of the R1 coiled
      coil repeat when bound to the membrane lipids. This model is totally in agreement
      with SANS and click chemistry/mass spectrometry data. We conclude that the
      sarcolemma membrane anchoring that occurs during the contraction/elongation
      process of muscles could be ensured by this coiled-coil opening. Therefore,
      understanding these structural changes may help in the design of rationalized
      shortened dystrophins for gene therapy. Finally, our strategy opens up new
      possibilities for structure determination of peripheral and integral membrane
      proteins not compatible with different high-resolution structural methods.

PMID- 30197183
TI  - Clinical guidelines on the diagnosis and treatment of celiac disease in Mexico.
AB  - Celiac disease, celiac sprue, or gluten-sensitive enteropathy, is a generalized
      autoimmune disease characterized by chronic inflammation and atrophy of the small
      bowel mucosa. It is caused by dietary exposure to gluten and affects genetically
      predisposed individuals. In Mexico, at least 800,000 are estimated to possibly
      have the disease, prompting the Asociacion Mexicana de Gastroenterologia to
      summon a multidisciplinary group of experts to develop the "Clinical guidelines
      on the diagnosis and treatment of celiac disease in Mexico" and establish
      recommendations for the medical community, its patients, and the general
      population. The participating medical professionals were divided into three
      working groups and were given the selected bibliographic material by the
      coordinators (ART, LUD, JMRT), who proposed the statements that were discussed
      and voted upon in three sessions: two voting rounds were carried out
      electronically and one at a face-to-face meeting. Thirty-nine statements were
      accepted, and once approved, were developed and revised by the coordinators, and
      their final version was approved by all the participants. It was emphasized in
      the document that epidemiology and risk factors associated with celiac disease
      (first-degree relatives, autoimmune diseases, high-risk populations) in Mexico
      are similar to those described in other parts of the world. Standards for
      diagnosing the disease and its appropriate treatment in the Mexican patient were
      established. The guidelines also highlighted the fact that a strict gluten-free
      diet is essential only in persons with confirmed celiac disease, and that the
      role of gluten is still a subject of debate in relation to nonceliac, gluten
      sensitive patients.

PMID- 30197184
TI  - Graves' disease and celiac disease in a patient with myotonic dystrophy type 2.
AB  - We report a patient with progressive proximal muscle weakness in her legs, early
      onset cataract and perceptive hearing loss, who was recently diagnosed with
      myotonic dystrophy type 2 (DM2). She also had two autoimmune disorders in her
      history, namely Graves' disease and celiac disease. Previous studies have shown a
      high frequency of autoimmune diseases (21%) in patients with DM2. This is the
      first report of a patient with DM2 and two autoimmune diseases which both have
      not yet been described in DM2. The cause of this association might be explained
      at DNA, mRNA and protein levels, including genetic mutation in flanking genes and
      the toxic effect of the DM2 mutation on proteins involved in inflammation. This
      case report widens the spectrum of autoimmune diseases in DM2 and has
      implications both for clinical practice and for research.

PMID- 30197185
TI  - CISH is a negative regulator of IL-13-induced CCL26 production in lung
      fibroblasts.
AB  - BACKGROUND: Bronchial asthma is a chronic airway disease characterized by
      eosinophilic airway inflammation. Lung fibroblasts activated by IL-13 serve as
      important sources of chemokines, such as eotaxins, contributing to persistent
      eosinophilic inflammation. Src-homology 2-containing protein (CISH), belonging to
      the suppressor of cytokine signaling (SOCS) family, acts as a negative regulator
      of cytokine induction. The aim of this study was to elucidate the role of CISH in
      the production of eosinophil chemotactic chemokines in human lung fibroblasts.
      METHODS: Normal human lung fibroblasts were stimulated by IL-13, and global gene
      expression profile was assessed by cDNA microarray. Expression changes and
      downstream of IL-13 signaling were evaluated by quantitative RT-PCR, ELISA or
      western blotting. Loss- and gain-of-function analyses of CISH were performed by
      small interfering RNA and vector overexpression, respectively. RESULTS: Ingenuity
      pathway analysis revealed that IL-13 induced chemokine signaling, including the
      eotaxin family, while significantly suppressing IFN-alpha/beta signaling. Among
      eight SOCS family members, CISH was most strongly induced by IL-13 via
      phosphorylation of signal transducer and activator of transcription 6 (STAT6).
      Loss- and gain-of-function studies demonstrated that CISH negatively regulated
      the expression of CCL26. CONCLUSIONS: These findings suggest that CISH plays a
      key role in the eosinophilic inflammation associated with bronchial asthma by
      regulating IL-13-induced CCL26 production. Augmentation of CISH function could be
      a novel approach for treating eosinophilic inflammation in severe asthma.

PMID- 30197186
TI  - A motivational phone call improves participation to screening colonoscopy for
      those with a positive FIT in a national screening programme (NCT 03276091).
AB  - BACKGROUND: A large proportion of individuals with a positive faecal immunologic
      test (FIT) will never undergo the recommended colonoscopy despite a full sequence
      of reminders. AIMS: This prospective study aimed to recruit refractory
      individuals by a motivational personalised phone call given by a screening
      physician. METHODS: We evaluated the impact of a motivational phone call given by
      a physician of the screening organisation in order to convince patients with
      positive FIT to undergo a colonoscopy. RESULTS: 115 individuals with a positive
      FIT were targeted. After GP phone call, it was ascertained that 15 had had a
      colonoscopy, one died, one moved outside the region, and the GP refused the study
      phone call for 13. Finally, we attempted to call 85 individuals; 24 could not be
      reached, 5 colonoscopies had been performed, and thus 56 individuals were
      included. The main reason for colonoscopy refusal (33.9%) was wrong advice from
      the GP or the gastroenterologist. Among those included, 33.9% (19/56) underwent
      the colonoscopy within 22.7 months after FIT; 1 invasive cancer, 18 adenomas and
      9 serrated sessile lesions were found. CONCLUSION: Motivational phone call
      performed by a physician from the screening organisation is effective to recruit
      a third of refractory individuals. Education for GPs and gastroenterologists is
      necessary to increase participation to colonoscopy and to avoid the performance
      of an inappropriate secondary FIT. TRIAL REGISTRATION: NCT 03276091.

PMID- 30197187
TI  - Epidemiology of inflammatory bowel disease in the Republic of San Marino: The
      "EPIMICI - San Marino" study.
AB  - BACKGROUND: The burden of Crohn's disease (CD) and ulcerative colitis (UC) has
      never been estimated in the Republic of San Marino, the third smallest nation of
      the world. AIMS: To assess the occurrence and clinical features of CD and UC in
      San Marino during the last 35 years. METHODS: We retrospectively evaluated the
      prevalence, incidence, and main clinical aspects of CD and UC from 1980 to 2014,
      crossing data from various sources. RESULTS: Prevalence rates (per 100,000) on
      December 31, were 241 for CD (263 in males and 220 in females) and 311 for UC
      (370 in males and 255 in females). The specific incidence of UC steadily
      increased from 4.6 (95% CI: 1.5-10.6) in 1980-1984 to 12.4 (95% CI: 7.6-19.1) in
      2010-2014; CD incidence showed a higher proportional increase, from 1.8 (95% CI:
      0.2-6.6) in 1980-1984 to 17.9 (95% CI: 12.0-25.7) in 2010-2014. The main clinical
      features of CD and UC (activity and location at diagnosis, extra-intestinal
      manifestations, disease progression overtime, therapies, and hospitalizations)
      were analyzed. CONCLUSIONS: This study provides the first epidemiological report
      on CD and UC in San Marino, showing specific traits and overall higher prevalence
      and incidence rates than previously reported in neighbor Areas.

PMID- 30197188
TI  - ?
AB  - We report cases of delayed, sustained elevated intraocular pressure (IOP)
      associated with repeated intravitreal anti-VEGF injections (IVI), which
      ultimately resulted in the need for filtering surgery. Two of the three cases
      demonstrated severe IOP elevation despite maximal medical treatment following
      unilateral IVI and required urgent filtering surgery. Optic nerve involvement was
      severe in all three cases. These intravitreal injections were performed for
      exudative age-related macular degeneration (AMD), and the patients did not show
      any sign of glaucoma or ocular hypertension prior to the initiation of treatment.
      Elevated IOP secondary to intravitreal steroids is a well-known side effect, as
      is immediate transient IOP elevation associated with anti-VEGF injection. Late,
      sustained IOP elevation after repeated injections of anti-VEGF, described
      approximately ten years ago, is often underestimated. Its incidence is estimated
      between 2.1 % and 13 % according to studies and increases with the number of IVI
      (cumulative effect). The pathophysiologic process is becoming increasingly
      understood, and several risk factors for this chronic IOP elevation have been
      identified. Most often, it is a moderate IOP elevation for which topical
      monotherapy is sufficient, or sometimes two, three or four medications or even
      selective laser trabeculoplasty (SLT). However, filtering surgery may rarely be
      required. Our findings illustrate a little-described phenomenon: a sudden,
      severe, late IOP elevation in response to anti-VEGF by an "overflow" effect,
      requiring urgent filtering surgery.

PMID- 30197189
TI  - Correlations between peripapillary retinal nerve fiber layer thickness and
      macular thickness in different various stages of primary open-angle glaucoma.
AB  - PURPOSE: To determine the relationship between macular thickness and
      peripapillary retinal nerve fiber layer (RNFLp) thickness in different stages of
      primary open-angle glaucoma (POAG). METHODS: Ninety prospectively selected
      patients with different stage POAG underwent spectral domain optical coherence
      tomography (SD-OCT) to determine macular and RNFLp thicknesses in different
      regions and sectors respectively. Correlations were then established through
      Pearson's correlation coefficient between RNFLp and macular thicknesses in the
      different disease stages. RESULTS: Greatest correlation was observed between the
      inferior RNFLp sector and the internal inferior macula both in the whole patient
      population and in the subset of patients with incipient glaucoma. CONCLUSIONS:
      When the optic nerve disc is affected by another condition, macular thickness
      determination may help detect POAG and monitor its progression.

PMID- 30197191
TI  - Genetics and myocardial infarction.

PMID- 30197190
TI  - [A case of congenital cerulean cataract].

PMID- 30197192
TI  - Tetralogy of Fallot after repair: A heritage of modern cardiac surgery.

PMID- 30197193
TI  - Reactive Persulfides from Salmonella Typhimurium Downregulate Autophagy-Mediated
      Innate Immunity in Macrophages by Inhibiting Electrophilic Signaling.
AB  - Reactive persulfides such as cysteine persulfide and glutathione persulfide are
      produced by bacteria including Salmonella during sulfur metabolism. The
      biological significance of bacterial reactive persulfides in host-pathogen
      interactions still warrants investigation. We found that reactive persulfides
      produced by Salmonella Typhimurium LT2 regulate macrophage autophagy via
      metabolizing 8-nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP), an
      electrophilic product of reactive oxygen species and nitric oxide signaling. 8
      Nitro-cGMP signaling was required for efficient autophagy-mediated clearance of
      Salmonella from infected macrophages. In the infected cells, 8-nitro-cGMP caused
      cGMP adduct formation (S-guanylation) of bacterial surface proteins, which
      triggered recruitment of autophagy-related proteins p62 and LC3-II to the
      intracellular bacteria. We also found that Salmonella-produced reactive
      persulfides downregulated this autophagy by decreasing cellular 8-nitro-cGMP
      content, thereby inhibiting electrophilic signaling. These data reveal a
      pathogenic role of bacteria-derived reactive persulfides via suppression of anti
      bacterial autophagy.

PMID- 30197194
TI  - Potent alpha-Synuclein Aggregation Inhibitors, Identified by High-Throughput
      Screening, Mainly Target the Monomeric State.
AB  - alpha-Synuclein (alphaSN) aggregation is central to the etiology of Parkinson's
      disease (PD). Large-scale screening of compounds to identify aggregation
      inhibitors is challenged by stochastic alphaSN aggregation and difficulties in
      detecting early-stage oligomers (alphaSOs). We developed a high-throughput
      screening assay combining SDS-stimulated alphaSN aggregation with FRET to
      reproducibly detect initial stages in alphaSN aggregation. We screened 746,000
      compounds, leading to 58 hits that markedly inhibit alphaSN aggregation and
      reduce alphaSOs' membrane permeabilization activity. The most effective
      aggregation inhibitors were derivatives of (4-hydroxynaphthalen-1-yl)sulfonamide.
      They interacted strongly with the N-terminal part of monomeric alphaSN and
      reduced alphaSO-membrane interactions, possibly by affecting electrostatic
      interactions. Several compounds reduced alphaSO toxicity toward neuronal cell
      lines. The inhibitors introduced chemical modifications of alphaSN that were,
      however, not a prerequisite for inhibitory activity. We also identified several
      phenyl-benzoxazol compounds that promoted alphaSN aggregation (proaggregators).
      These compounds may be useful tools to modulate alphaSN aggregation in cellula.

PMID- 30197195
TI  - Small Molecule Targeting of Specific BAF (mSWI/SNF) Complexes for HIV Latency
      Reversal.
AB  - The persistence of a pool of latently HIV-1-infected cells despite combination
      anti-retroviral therapy treatment is the major roadblock for a cure. The BAF
      (mammalian SWI/SNF) chromatin remodeling complex is involved in establishing and
      maintaining viral latency, making it an attractive drug target for HIV-1 latency
      reversal. Here we report a high-throughput screen for inhibitors of BAF-mediated
      transcription in cells and the subsequent identification of a 12-membered
      macrolactam. This compound binds ARID1A-specific BAF complexes, prevents
      nucleosomal positioning, and relieves transcriptional repression of HIV-1.
      Through this mechanism, these compounds are able to reverse HIV-1 latency in an
      in vitro T cell line, an ex vivo primary cell model of HIV-1 latency, and in
      patient CD4+ T cells without toxicity or T cell activation. These macrolactams
      represent a class of latency reversal agents with unique mechanism of action, and
      can be combined with other latency reversal agents to improve reservoir
      targeting.

PMID- 30197196
TI  - Dectin-1 on macrophages modulates the immune response to Fasciola hepatica
      products through the ERK signaling pathway.
AB  - Fasciolosis is a zoonotic disease of increasing importance due to its worldwide
      distribution and elevated economic losses. Previously, we demonstrated that
      Fasciola hepatica excretory-secretory products (FhESP) induce immunomodulatory
      effects on peritoneal macrophages in a Dectin-1 dependent manner. In this study,
      we observed that peritoneal macrophages from naive BALB/c mice stimulated in
      vitro with FhESP presented increased expression levels of phosphorylated
      extracellular-signal-regulated kinase (ERK), and this effect was dependent on
      Syk, protein kinase C (PKC) and Dectin-1. In this sense, we observed increased
      levels of arginase activity, IL-10 and TGF-beta in macrophages stimulated with
      FhESP, which were dependent on PKC and ERK. Furthermore, we observed that the
      increased arginase activity, as well as in TGF-beta and IL-10 levels, was
      partially dependent on IL-10 receptor signaling in macrophages that were pre
      incubated with anti-IL10R before being stimulated with FhESP. Taken together,
      these results suggest the participation of Dectin-1 and Syk in FhESP interaction
      with peritoneal macrophages and the possible role of ERK and IL-10 in downstream
      signaling pathways involved in the immunomodulatory effects induced by Fasciola
      hepatica products.

PMID- 30197197
TI  - Surveillance or Safekeeping? How School Security Officer and Camera Presence
      Influence Students' Perceptions of Safety, Equity, and Support.
AB  - PURPOSE: Target hardening, or increasing the use of security measures, is a
      frequently used response to perceived safety concerns in schools. Studies are
      mixed as to their effectiveness on students' perceptions of safety and little is
      known about their influence on other aspects of school climate, particularly for
      minority students. This study will examine the association between observed
      security measures in secondary schools and students' perceptions of safety,
      equity, and support. METHODS: School climate surveys were completed by 54,350
      students from 98 middle and high schools across the state of Maryland beginning
      in Spring 2014. Concurrent observations of the school physical environment,
      including security measures (i.e., officers and cameras), were conducted by
      trained outside assessors. Multilevel regression analyses examined the
      association between school security officers and cameras and students'
      perceptions of safety, equity, and support, while controlling for school and
      neighborhood characteristics. Cross-level interactions explored differential
      effects of security measures for Black students. RESULTS: Greater use of security
      cameras inside the school was related to lower perceptions of safety, equity, and
      support. A moderate level of security camera use outside the school was related
      to higher student perceptions of support. Security officer presence was
      associated with higher perceptions of safety. For black students, cameras were
      associated with elevated perceptions of safety and support relative to white
      students. CONCLUSIONS: Our findings may suggest that outside cameras and security
      may be perceived by students as safekeeping, whereas inside cameras may evoke
      feelings of being viewed as potential perpetrators who need surveillance.

PMID- 30197198
TI  - Effectiveness and Behavioral Mechanisms of Social Media Interventions for
      Positive Nutrition Behaviors in Adolescents: A Systematic Review.
AB  - PURPOSE: To determine the effectiveness of social media-based interventions in
      promoting positive changes in nutrition behaviors amongst adolescents, and
      identify the behavior change technique(s) (BCT(s)) that were used in effective
      interventions. METHODS: MEDLINE, Embase, PsycINFO, Cinahl, and Cochrane library
      were systematically searched. Eligible studies included: participants aged 13-18
      years; use of one or more social media platform(s) in the intervention; a
      comparison group not exposed to the social media-based intervention; nutrition-
      and diet-related behavior outcome(s); and an experimental study design. BCTs were
      identified using a behavior change taxonomy. Quality and risk of bias assessments
      were also conducted. RESULTS: Seven eligible interventions were included, varying
      from internet-only programs to in-person programs with internet or website-based
      component(s). Studies used relatively outdated forms of social media such as
      purpose-built discussion boards or chat rooms rather than commercial social media
      interfaces (e.g. Facebook). Five of the seven interventions demonstrated
      improvements in at least one nutrition behavior. The most common improvement was
      for fruit or vegetable intake, and two of four studies showed improvements for
      sugar-sweetened beverage consumption. The most common BCT used was social
      support, followed by demonstration of behavior, self-monitoring, goal setting,
      and feedback. CONCLUSIONS: The current evidence base is equivocal with respect to
      changing overall dietary behaviors, as increasing intakes of desirable food
      groups were more successful than decreasing unfavorable food habits. Further
      research using better quality interventions, full description of the BCTs, long
      term follow-up, and popular contemporary social media platforms to build the
      evidence base are required.

PMID- 30197199
TI  - Young Women's Experiences Obtaining Judicial Bypass for Abortion in Texas.
AB  - PURPOSE: Like many states, Texas requires parental consent for adolescents under
      18 to access abortion care. Adolescents who cannot obtain parental consent can
      try to obtain a judicial bypass of parental consent through the court system.
      Little is known about adolescents' experiences with the judicial bypass process.
      Working with Jane's Due Process, an organization providing legal representation
      for adolescents, we explored adolescents' experiences with the judicial bypass
      process. METHODS: We conducted phone interviews with 20 adolescents, 16-19years
      old in Texas between September and December 2016 about their experiences trying
      to obtain a judicial bypass. Data analysis included inductive and deductive
      coding based on theories about engaging with the court system and stigma
      regarding abortion and adolescent sexuality. RESULTS: In addition to
      unpredictability and logistic burdens such as finding time away from school and
      arranging transportation, participants described the bypass process as
      "intimidating" and "scary" and described judges and guardians-ad-litem who shamed
      them, "preached" at them, and discredited evidence of their maturity. Data
      suggest adolescents internalize stigma and trauma they experienced through
      rationalizing both the need for the bypass process and disrespectful treatment by
      authority figures. CONCLUSIONS: We found the bypass process functions as a form
      of punishment and allows state actors to humiliate adolescents for their personal
      decisions. The bypass process was implemented to protect adolescents from alleged
      negative emotional consequences of abortion, yet our results suggest the bypass
      process itself causes emotional harm through unpredictability and humiliation.
      Despite participants' resilience, the process may have negative consequences for
      adolescent health.

PMID- 30197200
TI  - Maternal Lifetime Trauma and Birthweight: Effect Modification by In Utero
      Cortisol and Child Sex.
AB  - OBJECTIVES: To evaluate associations between maternal lifetime traumatic stress
      and offspring birthweight and examine modifying effects of third trimester
      cortisol and fetal sex. STUDY DESIGN: Analyses included 314 mother-infant dyads
      from an ethnically mixed pregnancy cohort. Maternal lifetime trauma was reported
      via the Life Stressor Checklist-Revised. Fenton birthweight for gestational age z
      scores (BWGA-z) were calculated. A 3-cm scalp-nearest maternal hair segment
      collected at birth was assayed to reflect cumulative third trimester cortisol
      secretion. Multivariable regression was used to investigate associations between
      maternal lifetime trauma and BWGA-z and examine 2- and 3-way interactions with
      cortisol and fetal sex. Because subjects with low or high cortisol levels could
      represent susceptible populations, varying coefficient models that relax the
      linearity assumption on cortisol level were used to assess the modification of
      maternal lifetime trauma associations with BWGA-z as a function of cortisol.
      RESULTS: Women were primarily minorities (41% Hispanic, 26% black) with <=12
      years education (63%); 63% reported >=1 traumatic event. Prenatal cortisol
      modified the association between maternal lifetime trauma and birthweight. Women
      with higher lifetime trauma and increased cortisol had significantly lower
      birthweight infants in males; among males exposed to the 90th percentile of
      cortisol, a 1-unit increase in trauma score was associated with a 0.19-unit
      decrease in BWGA-z (95% CI, -0.34 to -0.04). Associations among females were
      nonsignificant, regardless of cortisol level. CONCLUSIONS: These findings
      underscore the need to consider complex interactions among maternal trauma,
      disrupted in utero cortisol production, and fetal sex to fully elucidate
      intergenerational effects of maternal lifetime trauma.

PMID- 30197201
TI  - Early Glycemic Profile Is Associated with Brain Injury Patterns on Magnetic
      Resonance Imaging in Hypoxic Ischemic Encephalopathy.
AB  - OBJECTIVE: To investigate whether the early glycemic profile in infants with
      hypoxic ischemic encephalopathy is associated with distinct patterns of brain
      injury on magnetic resonance imaging (MRI). STUDY DESIGN: We performed a
      secondary analysis of 178 prospectively enrolled infants who received therapeutic
      hypothermia for hypoxic ischemic encephalopathy. Glycemic profiles were
      identified by glucose concentrations within 24 hours after birth: normoglycemia
      (all glucose concentrations of >47 to <=150 mg/dL; n = 62); hypoglycemia (>=1
      concentration <=47 mg/dL; n = 17); hyperglycemia (>=1 concentration >150 mg/dL; n
      = 76); and labile glucose (both hypoglycemia and hyperglycemia; n = 23). Patterns
      of brain injury were identified for 151 infants based on Barkovich scores from
      the postrewarming brain MRIs at a median age of 9 days. RESULTS: A normal brain
      MRI was reported in 37 of 62 infants (60%) with normal blood glucose values
      compared with 37 of 116 infants (32%) with an abnormal glucose profile (adjusted
      for Sarnat stage of encephalopathy and Apgar score at 5 minutes; P = .02). The
      distribution of MRI patterns of brain injury differed among the glycemic groups
      (P = .03). The odds of predominant watershed or focal-multifocal injury was
      higher in infants with hypoglycemia (aOR, 6; 95% CI, 1.5-24.2) and labile glucose
      (6.6; 95% CI, 1.6-27) compared with infants with normoglycemia. Infants with
      labile glucose had higher odds (5.6; 95% CI, 1.1-29.3) of predominant basal
      ganglia or global injury compared with infants with normal blood glucose values.
      CONCLUSIONS: The early glycemic profile in infants with hypoxic ischemic
      encephalopathy is associated with specific patterns of brain injury on MRI.
      Further investigation is needed to explore its prognostic significance and role
      as a phenotype biomarker.

PMID- 30197202
TI  - Comparison of Modified Transtibial and Outside-In Techniques in Anatomic Single
      Bundle Anterior Cruciate Ligament Reconstruction.
AB  - PURPOSE: To compare the bending angle of anterior cruciate ligament (ACL) graft
      at femoral tunnel, graft maturation, and tunnel positions and the clinical
      outcomes of the modified transtibial (mTT) and outside-in (OI) techniques.
      METHODS: Patients who met the inclusion criteria were divided into the mTT group
      (n = 50) and the OI group (n = 50). Using 3-dimensional computed tomography (3-D
      CT), tunnel placement and femoral tunnel bending angle were analyzed. The 3.0-T
      magnetic resonance imaging (MRI) was used to assess the graft signal intensity
      (indicative of maturation) with signal/noise quotient (SNQ). Graft tension and
      synovialization were evaluated with second-look arthroscopy in all cases.
      Clinical and functional tests were completed at 36 months of follow-up. RESULTS:
      When tunnel placements were analyzed using the quadrant method, no significant
      differences were found between the mTT group and the OI group. The femoral graft
      bending angle was reduced in the mTT group, and the total mean of SNQ values and
      mean SNQ values at the femoral intraosseous and proximal graft of the mTT group
      were significantly lower than in the OI group (P < .001), respectively. The
      femoral graft bending angle on the coronal and axial planes showed moderate-to
      strong correlation with the SNQ values at the femoral intraosseous and proximal
      graft. Second-look arthroscopy revealed better synovialization in the mTT group
      than in the OI group (P = .040), with no significant difference in graft tension
      between the 2 groups (P = .328). CONCLUSIONS: Anatomic tunnel placements did not
      vary between the mTT group and the OI group. However, the mTT group had more
      benefits in femoral graft bending angle and showed higher graft maturity and
      better synovial coverage than the OI group, although there were no significant
      differences in clinical outcomes. The acute femoral graft bending angle might
      negatively affect the maturation of proximal graft. LEVEL OF EVIDENCE: Level III,
      retrospective comparative study.

PMID- 30197203
TI  - Commentary to "Improving surgical training by identifying the most common
      feedback trainees require for index cases".

PMID- 30197204
TI  - Correlation between the length from the elbow to the distal interphalangeal joint
      of the little finger and the length of the intramedullary nail selected for
      femoral fracture fixation.
AB  - AIM: To determine whether there is a correlation between the length of forearm to
      the distal interphalangeal joint (DIPJ) of the little finger and length of
      antegrade intramedullary (IM) femoral nails in adults. STUDY DESIGN AND METHODS:
      Measurements from the tip of the olecranon to the DIPJ of the ipsilateral upper
      limb was taken in 30 patients undergoing antegrade IM femoral nails. The length
      of the IM nails inserted was determined by intra-operative measurements using a
      guide wire. The two measurements were analysed for correlation and mean
      difference. RESULTS: The mean forearm to DIP of little finger length was 38.86
      with a standard deviation of 2.83. The mean IM length and standard deviation were
      38.56 and 2.77 respectively. The difference between the two means 0.3 (95% CI).
      Correlation testing between the two variables shows a positive relationship
      (Pearson Correlation factor of 1). The scatter plot shows a positive linear
      relationship. CONCLUSIONS: Length of the forearm from the tip of the olecranon to
      the DIP joint of the little finger represents the ideal length of IM nail for the
      femur. It can be readily performed with the use of a tape measure and can serve
      as a useful adjunct to determining ideal length in cases where the contralateral
      femur cannot be used.

PMID- 30197205
TI  - Cycling related traumatic brain injury requiring intensive care: association with
      non-helmet wearing in young people.
AB  - INTRODUCTION: Traumatic injury is the leading cause of death in children after
      infancy. Almost 25% of all cyclists killed in the UK are children, and two thirds
      of these will die because of their head injuries. We compared the population of
      young people wearing helmets whilst cycling, to those admitted with serious post
      cycling head injuries to our paediatric critical care unit. METHOD: All children
      aged 0-18 years admitted to our intensive care following a bicycle accident
      between the years January 2011-June 2018 were identified and information on the
      mechanism of injury, and both immediate and long term clinical data were
      collected. For comparison data, helmet wearing on a random morning was observed
      from six schools. All pupils arriving at school by bicycle were observed. Data
      collected included the school year and sex of the child, and whether each child
      was wearing a helmet or not. RESULTS: Of 28 cases, 22 were admitted due to head
      injuries. None wore a helmet. 23/133 school pupils wore a helmet. The intensive
      care population were significantly less likely to be wearing helmets than the
      general population (p = 0.044, Fisher's exact test). A Chi-Square test for helmet
      wearing by school year showed a reduction in helmet wearing with increasing
      school year with a p value of 0.0026. There was no association between helmet
      wearing and abdominal injury. CONCLUSION: Young people admitted to a Critical
      Care Unit with cycling related head trauma are statistically significantly less
      likely to wear a helmet than the general, age matched cycling population. Helmet
      wearing decreases as children get older. Outcomes were mixed, but in the head
      trauma group only 3/18 recovered with no neurological deficit.

PMID- 30197206
TI  - How older adults with multimorbidity manage their own care within a formal care
      coordination program?
AB  - As the number of older adults with multimorbidity increases, care coordination
      programs are being designed to streamline the complex care older adults receive
      from multiple providers by improving health and reducing unnecessary costs. Well
      coordinated care requires actions by both patients and providers. Yet little
      attention is paid to the what older adults do to manage their own care alongside
      a formal Care Coordination Program (CCP). This paper presents a qualitative
      descriptive study that explored what actions older adults took on their own to
      manage their care. Findings from this study identified that there were two
      actions older adults took to manage their care; they lived within their limits
      and they lived with grit. This study suggests that by recognizing what older
      adults do to self-manage their care within the context of a CCP, nurses can build
      on older adults' actions and provide person-centered strategies for care
      coordination.

PMID- 30197207
TI  - The Skiles Mummy: Care of a debilitated hunter-gatherer evidenced by coprolite
      studies and stable isotopic analysis of hair.
AB  - The Skiles Mummy (SMM), a naturally mummified adult male from the late archaic
      period of Lower Pecos Canyonlands of South Texas, represents a unique case of
      care. SMM is an exceptional mummy within this region due to both the retention of
      a full head of hair, and having a diagnosed case of megacolon, a complication
      commonly associated with Chagas disease caused by Trypanosoma cruzi. Stable
      isotopic analysis of his hair is consistent with a diet incorporating of C4/CAM
      plants with some C3 plants, freshwater resources, and higher trophic level
      animals. However, the segments of hair most proximal to the scalp exhibited
      elevated delta15N values. Data from previous research indicate starvation and
      malnutrition can cause delta15N values to rise. The presence of large fecal
      boluses in the digestive tract suggest peristalsis ceased in the last four to
      five months of life, and this, together with results from coprolite analysis,
      indicate he would not have been able to adequately absorb protein and nutrients
      during this time. His condition would have rendered him immobile. Following
      Tilley's index of care, someone would have had to bring him food resources, as
      well as attending to his daily needs.

PMID- 30197208
TI  - A comparison of modelling options to assess annual variation in susceptibility of
      generic Escherichia coli isolates to ceftiofur, ampicillin and nalidixic acid
      from retail chicken meat in Canada.
AB  - Statistical modelling of antimicrobial resistance (AMR) data is an important
      aspect of AMR surveillance programs; however, minimum inhibitory concentration
      (MIC) data can be challenging to model. The conventional approach is to
      dichotomize data using established breakpoints, then use logistic regression
      modelling for analysis. A disadvantage of this approach is a loss of information
      created by dichotomizing the data. The objectives of the study were to compare
      the performance and results of different regression models for the analysis of
      annual variation in susceptibility of generic Escherichia coli (E. coli) isolates
      to ceftiofur, ampicillin and nalidixic acid from retail chicken meat surveillance
      samples. E. coli susceptibility data for the three antimicrobials from retail
      chicken samples from 2007 to 2014 were obtained from the Canadian Integrated
      Program for Antimicrobial Resistance Surveillance (CIPARS). Annual variation in
      susceptibility for each antimicrobial was evaluated using multivariable linear,
      tobit, logistic, multinomial, ordinal and complementary log-log regression models
      (clog-log). MIC (log2), censored MIC (log2), resistant/susceptible, and
      categorized MIC (3 or 4 categories) data were used as outcome variables for the
      appropriate statistical models. Year and region were modelled as categorical
      predictor variables. Random intercepts were included in the ceftiofur and
      ampicillin models to account for clustering by retail establishment. The model
      assumptions evaluated for the mixed models included homoscedasticity and
      normality of residuals (linear and tobit), homoscedasticity and normality of best
      linear unbiased predictions (all models), proportional odds (ordinal), and
      proportional hazards (clog-log). Fixed effects models were used for the nalidixic
      acid models. The model assumptions evaluated for the fixed effects models
      included homoscedasticity and normality of residuals (linear and tobit), goodness
      of-fit test (logistic and multinomial), proportional odds (ordinal), and
      proportional hazards (clog-log).Only logistic and multinomial models met model
      assumptions. Significant annual variation in susceptibility to all three
      antimicrobials was identified by the multinomial regression models, whereas the
      logistic regression models only identified significant annual variation in
      susceptibility to ceftiofur. The multinomial regression model consistently
      identified additional significant annual variation in susceptibility compared to
      the logistic regression model. The multinomial modelling approach was able to
      identify differences between MIC categories within susceptible MIC values, which
      were below the breakpoint (R) detection level. Given the convention of
      dichotomizing susceptibility data, the logistic regression approach is likely to
      remain the standard method of analysis for AMR surveillance data; however, the
      results of this study demonstrate that multinomial regression should be
      considered for the analysis of AMR surveillance data.

PMID- 30197209
TI  - Advancing from a "hemodynamic model" to a "mechanistic disease-modifying model"
      of cardiogenic shock.
AB  - Emerging clinical evidence has suggested that short-term mechanical augmentation
      of cardiac output (CO) may not consistently improve mortality in patients with
      cardiogenic shock (CS), despite improvements in hemodynamics. Such failures could
      reflect the underlying complexity of the mechanisms that contribute to
      malperfusion and organ dysfunction in CS. Distinct molecular and physiologic
      shock endophenotypes likely exist among patients with CS, with hemodynamic
      aberrations as the inciting insult but not necessarily the primary drivers of
      clinical outcomes. We propose that building a framework that moves away from the
      current "hemodynamic model" in preference for a "mechanistic disease-modifying
      model" of CS may facilitate progress toward reducing the stagnant mortality rates
      in this population. Such a therapeutic paradigm shift in patients with chronic
      systolic heart failure-the shift away from strategies that augment CO to those
      that modulate the systemic responses to low CO-has been one of the single most
      important shifts in contemporary cardiovascular medicine.

PMID- 30197210
TI  - Euthanasia through living organ donation: Ethical, legal, and medical challenges.
AB  - Euthanasia is categorically prohibited in almost all countries throughout the
      world. In Belgium and the Netherlands, combining euthanasia and subsequent organ
      donation in a so-called donation after circulatory-death (DCD) procedure is
      feasible on legal and medical grounds, and is increasingly gaining social and
      ethical acceptance. However, heart transplantation after DCD is currently not
      performed in Belgium and the Netherlands after euthanasia due to concerns
      surrounding the prolonged warm ischemia time associated with DCD and its effect
      on subsequent heart function. A number of patients who undergo euthanasia
      explicitly express their wish to donate their organs in a "living organ donation"
      procedure, which then causes death. Assuming that euthanasia is permitted, as
      expressed in Dutch and Belgian legislation, this exploratory article addresses
      whether it is legally and ethically sound to donate organs, especially the heart,
      as a living donor and to perform euthanasia in the same procedure in a patient
      who fulfills the due diligence requirements for euthanasia. Organ donation
      euthanasia (ODE) would then cause death by the associated surgical procedure, and
      in addition would improve the quality of the other donated organs, a procedure
      that would fully respect the patient's autonomy.

PMID- 30197211
TI  - Aortic regurgitation in patients with a left ventricular assist device: A
      contemporary review.
AB  - Aortic regurgitation (AR) developing while using a continuous-flow left
      ventricular assist device (CF-LVAD) affects 25% to 30% of patients within the
      first year of implantation and is increasingly being recognized as a cause of
      recurrence of symptomatic heart failure (HF). The underlying mechanisms are
      likely multifactorial, including changes in the leaflets of the aortic valve
      (AV), altered root biomechanics, and excessive left ventricular (LV) unloading,
      together promoting cusp remodeling and commissural fusion. Known risk factors for
      the development of AR while under support include advanced age, lower body
      surface area, systemic hypertension, large aortic root diameter, permanently
      closed AV, and duration of support. Further, variants in the anastomotic angle
      between the outflow graft and the ascending aorta have recently been recognized
      to induce structural changes in the aortic wall, contributing to the development
      and progression of AV disease. Nevertheless, it remains controversial as to
      whether AR on LVAD has an independent impact on prognosis, and no clear
      recommendation exists regarding its optimal diagnosis criteria and treatment.
      Herein we briefly review the literature and focus on the latest results regarding
      development of AR in patients supported with CF-LVADs. We also provide a
      structured echocardiographic approach for an accurate assessment of AV
      dysfunction in this challenging situation.

PMID- 30197212
TI  - Relevance of phenotypic information for the taxonomy of not-yet-cultured
      microorganisms.
AB  - To date, far less than 1% of the estimated global species of Bacteria and Archaea
      have been described and their names validly published. Aside from these
      quantitative limitations, our understanding of phenotypic and functional
      diversity of prokaryotes is also highly biased as not a single species has been
      described for 85 of the 118 phyla that are currently recognized. Due to recent
      advances in sequencing technology and capacity, metagenomic datasets accumulate
      at an increasing speed and new bacterial and archaeal genome sequences become
      available at a faster rate than newly described species. The growing gap between
      the diversity of Bacteria and Archaea held in pure culture and that detected by
      molecular methods has led to the proposal to establish a formal nomenclature for
      not-yet-cultured taxa primarily based on sequence information. According to this
      proposal, the concept of Candidatus species would be extended to groups of
      closely related genome sequences and their names validly published following
      established rules of bacterial nomenclature. The corresponding sequences would be
      deposited in public databases as the type. The suggested alterations of the
      International Code of Nomenclature of Prokaryotes raise concerns regarding (1)
      the reliability and stability of nomenclature, (2) the technological and
      conceptual limitations as well as availability of reference genomes, (3) the
      information content of in silico functional predictions, and (4) the recognition
      of evolutionary units of microbial diversity. These challenges need to be
      overcome to arrive at a meaningful taxonomy of not-yet-cultured prokaryotes with
      so far poorly understood phenotypes.

PMID- 30197213
TI  - Application of the 3D digital ostectomy template (DOT) in mandibular angle
      ostectomy (MAO).
AB  - BACKGROUND: Mandibular angle ostectomy (MAO) is a standard approach in
      reconstruction of facial contour that is commonly used in East Asian patients
      with prominent mandibular angles (PMA). MAO is commonly performed via an
      intraoral approach to reduce scar visibility and risk of facial nerve injury.
      Since this intraoral approach for MAO has limited visual guidance during the
      procedure, plastic surgeons often perform the operation based on personal
      clinical experience. Therefore, we designed a 3D digital ostectomy template (DOT)
      for guidance during surgery to improve the accuracy and safety of MAO. METHODS:
      10 female patients (average age 25.3 years) with PMA were enrolled in this study
      from August 2014 to October 2015. The DOTs were designed and printed
      preoperatively and utilized in the operation to guide the osteotomy. The excised
      mandibular angle bone and the DOTs were measured respective to each other. The
      data were analyzed to verify the feasibility and safety of the DOT. RESULTS: All
      of the patients were satisfied with the surgical results, and no complications
      such as fracture, hemorrhage and infection occurred. The distance from gonion
      (Go) along inferior margin of mandible forward to the distal end of the excised
      bone is "a". The distance from Go along posterior margin of ramus upward to the
      distal end of the excised bone is "b". The widest distance from Go to the
      ostectomy line is denoted by "c". Similarly, the corresponding distance in the
      DOT is denoted by "a'", "b'", "c'". The statistical results showed that left a vs
      a', b vs b', c vs c' was 63.27 +/- 6.39 mm vs 62.97 +/- 6.30 mm (p > 0.05), 23.98
      +/- 2.25 mm vs 21.83 +/- 2.27 mm (p < 0.05), 13.58 +/- 2.24 mm vs 13.37 +/- 2.14
      mm (p > 0.05), respectively. The right a vs a', b vs b', c vs c' was 62.92 +/-
      5.00 mm vs 62.72 +/- 4.99 mm (p > 0.05), 24.03 +/- 1.88 mm vs 21.80 +/- 1.91 mm
      (p < 0.05), 13.36 +/- 1.70 mm vs 13.22 +/- 1.72 mm (p > 0.05), respectively. The
      results indicate a significant difference between b and b' both on the right and
      left sides. CONCLUSION: Through the application of DOT in MAO, the accuracy and
      safety of the operation were improved significantly. Unfortunately, the osteotomy
      could not be guided well in the posterior rim of the ramus. Further improvements
      in the surgical template are needed for application in PMA associated with
      oversized chin deformity or in PMA associated with large mandibular angle and
      severe involution.

PMID- 30197214
TI  - Pattern of distribution of 35 red cell antigens in regular voluntary blood donors
      of South Gujarat, India.
AB  - BACKGROUND: Extended phenotyping is one of the important method of reducing red
      cell alloimmunisation. Extended phenotyping of red cells from voluntary donors
      have many uses in addition to its application in population genetics. As there
      was very little data extended phenotyping on a cohort of Indian Voluntary blood
      donors this project was undertaken. STUDY DESIGN & METHODOLOGY: 200 regular
      voluntary blood donors having 'O' blood group were included for red cell antigen
      typing of Rh (D,C,E,c,e), Kell (K, k, Kpa, Kpb), Duffy (Fya, Fyb), Kidd (Jka,
      Jkb), Lewis(Lea, Leb), P(P1), MNS (M, N,S,s), and Lutheran (Lua, Lub), Colton
      (Coa, Cob), Diago (Diaa, Wra), Vw and Xga antigens using conventional antisera
      provided by DIAGAST. Calculations of antigen and phenotypes frequencies were
      expressed as percentages. RESULTS: Out of 200 'O' group blood donors, 96.5% were
      Rh D and 2.5% were K positive. Amongst Rh antigens, e was the most common (100%)
      followed by D, C (91.0%), c (50.5%) and E (16.5%) with DCe/DCe (R1R1, 48.0%)
      being the most common phenotype. In Kell blood group system, we found k antigen
      to be 100% and a rare phenotype Kp (a + b+) was found in 1% of the donors. For
      Kidd and Duffy blood group systems, Jk (a + b+) and Fy (a + b-) were the most
      common phenotypes (39.0% and 64.0%, respectively). In the MNS blood group system,
      M + N+ (67.5%) and S + s+(43.5%) were the most common phenotypes. There were
      antigens like Cw(3.5%), K(2.3%), Kpa(1.2%), Ina(1.0%), Vw(1.2%), Coa(4.5%),
      Cob(1%), Lua(1.75%), Dia+(1.2%), and Wra+(0.6%) with frequency < 5% in the donor
      population. CONCLUSION: Extensively antigen phenotypes group 'O' red cells showed
      significant variation with other population from India as well as with Caucasian
      and black population. Extensive phenotyping 'O' group regular blood donors of red
      cell antigens is very useful to prepare in-house red cell panels for
      identification of alloantibodies.

PMID- 30197215
TI  - Association Between Knee Malalignment and Ankle Degeneration in Patients With End
      Stage Knee Osteoarthritis.
AB  - BACKGROUND: The association between knee malalignment and ankle degeneration has
      not been well established. This study aimed at determining whether knee
      malalignment and compensatory ankle morphology to knee malalignment are
      associated with the development and progression of ankle osteoarthritis (OA) in
      patients with end-stage knee OA. METHODS: We retrospectively reviewed 96 patients
      (106 knees) who underwent total knee arthroplasty. The progression of ankle OA,
      knee alignment, and ankle morphology were evaluated based on digital radiographs.
      Alignment deformity of the lower extremity was evaluated with hip-knee-ankle
      angle and medial proximal tibial angle (MPTA). Ankle morphology was evaluated by
      the lateral distal tibial angle, talar tilt, tibial plafond inclination angle,
      and ankle joint line orientation angle. RESULTS: The incidence of radiological
      ankle OA was observed in 39 of 106 cases. The MPTA (odds ratio = 0.72, P = .0009)
      and hip-knee-ankle angle (odds ratio = 1.13, P = .0169) were significantly
      associated with ankle OA. Among patients with tibial varus deformity, 26 of 49
      had ankle OA. Among patients with neutral tibial alignment, 13 of 57 had
      radiological findings of ankle OA. MPTA was the only parameter associated with
      the progression of ankle OA. No association was observed between compensatory
      change in ankle morphology and the severity of ankle OA. CONCLUSION: Tibial varus
      deformity is associated with the development and progression of ankle OA;
      however, it is unclear whether it causes ankle OA. Due to the high incidence of
      ankle OA in total knee arthroplasty patients, it is reasonable to consider
      routine evaluation of the ankle.

PMID- 30197216
TI  - Increased Patellar Fracture Rate in Total Knee Arthroplasty With Preoperative
      Varus Greater Than 15 degrees : A Case-Control Study.
AB  - BACKGROUND: Management of severe varus deformity requires soft tissue balancing
      for implantation of low-constraint knee prosthesis. Patellar complications have
      been rarely studied in this specific group. Our hypothesis was that severe genu
      varum (>15 degrees ) would increase the rate of patellar complications. METHODS:
      Using a prospective cohort of 4216 prostheses performed at a single center
      beginning in 1987, we analyzed 280 prostheses having preoperative varus greater
      than 15 degrees , compared to 673 total knee arthroplasties (TKAs) with a
      preoperative hip-knee-ankle angle of 180 degrees  +/- 2 degrees . Preoperative
      and postoperative clinical and radiological characteristics were compared between
      the 2 groups, with particular attention paid to patellar complications. RESULTS:
      Average follow-up was 40.2 months (24-239). The mean preoperative Knee Society
      Score (KSS) was statistically higher in the normal (hip-knee-ankle angle 180
      degrees  +/- 2) axis group (62.65 vs 37.47, P = .001). At the last follow-up, no
      significant difference was found between the 2 groups in terms of postoperative
      KSS (87.5 in the varus group vs 87.3 in the normal axis group, P = .87). The rate
      of satisfied patients was identical between the 2 groups (85.3% vs 88.8%, P =
      .49). However, at mid-term, there were more patellar fractures in the varus group
      (2.9% vs 0.9%, P = .005). A significantly lower patellar height in both the varus
      group and the group of patella fractures (P < .001) was also found. CONCLUSION:
      TKA in severe varus knees produces a KSS equivalent to TKA in knees with a
      mechanical axis of 0 +/- 2. The risk of patellar fracture could initiate a
      decline in patella resurfacing in patients with major varus deformation,
      especially in case of a preoperative patella baja.

PMID- 30197217
TI  - Skilled Nursing Facilities After Total Knee Arthroplasty: The Time for Selective
      Partnerships Is Now!
AB  - BACKGROUND: Bundled payment initiatives for total knee arthroplasty (TKA)
      patients are dramatically impacted by discharges to skilled nursing facilities
      (SNFs), making target prices set by the Center for Medicare and Medicaid Services
      difficult to achieve. However, we hypothesized that a granular examination of SNF
      discharges would reveal that some may disproportionately increase costs compared
      to others. METHODS: The institutional database was retrospectively queried for
      primary TKA patients under bundled payment initiatives. The 4 most common SNFs
      utilized by our patient population (A, B, C, and D) were investigated for length
      of stay, cost of care, and whether the overall target price for the episode of
      care (EOC) was reached. RESULTS: In total, 1223 TKA patients were analyzed, with
      378 (30.9%) discharged to an SNF and 246 patients selecting one of the 4 most
      common SNFs (A: 198, B: 21, C: 15, D: 12). Each SNF represented a significant
      fiscal portion of the total EOC; however, SNF D had significantly longer length
      of stay (21 vs 13 days, P < .001) and cost of care ($11,805 vs $6015, P < .001)
      relative to the others, resulting in no EOC under the target price. SNF costs
      >24.6% of the total EOC were predictive of exceeding the target price.
      CONCLUSION: Bundled payment models are significantly impacted by SNF disposition;
      however, select facilities disproportionately impact this system. In order to
      maintain free patient selection for disposition, post-acute care facilities must
      be held accountable for controlling cost, or a separate bundled payment provided.

PMID- 30197218
TI  - Peripheral Nerve Blocks vs Periarticular Injections in Total Knee Arthroplasty.
AB  - In patients undergoing surgery, optimal pain management is associated with
      improved perioperative outcomes, patient satisfaction with surgery, and a more
      rapid functional recovery. In recent years, the employment of multimodal pain
      management strategies has become increasingly widespread. In particular, there
      has been an explosion in the use of peripheral nerve blockade and periarticular
      injections in total knee arthroplasty. However, there is significant variability
      in the administration of either modality of anesthesia. As such, a critical
      evaluation of the current literature is warranted to elucidate the advantages and
      disadvantages of each technique with the ultimate goal of further refining
      current pain control strategies. In this symposium, we review each of these
      modalities and their association with pain management, narcotic consumption,
      length of hospital stay, and adverse events.

PMID- 30197219
TI  - A Comparative Study Between Uncemented and Hybrid Total Hip Arthroplasty in
      Octogenarians.
AB  - BACKGROUND: The aim of this prospective cohort study is to evaluate the outcome
      of octogenarian patients undergoing uncemented total hip arthroplasty (THA) with
      a control group of similarly aged patients undergoing hybrid THA with a minimum 5
      year follow-up. METHODS: Clinical outcomes including intraoperative and
      postoperative complications, blood transfusion, revision rate, and mortality were
      recorded. Radiological analysis of preoperative and postoperative radiographs
      assessed bone quality, implant fixation, and any subsequent loosening. RESULTS:
      One hundred forty-three patients (mean age 86.2 years) were enrolled in the
      study. Seventy-six patients underwent uncemented THA and 67 underwent hybrid THA.
      The uncemented cohort had a significantly lower intraoperative complication rate
      (P = .017) and also a lower transfusion rate (P = .002). Mean hospital stay (P =
      .27) was comparable between the 2 groups. Two patients underwent revision surgery
      in each cohort. CONCLUSION: Our study demonstrates that uncemented THA is safe
      for the octogenarian patient and we recommend that age should not be a barrier to
      the choice of implant. However, intraoperative assessment of bone quality should
      guide surgeons to the optimum decision regarding uncemented and hybrid implants.
      LEVEL OF EVIDENCE: 3.

PMID- 30197220
TI  - Evaluation of Responsiveness to Reduced-Dose Rituximab in
      Corticotropin/Intravenous Immunoglobulin/Rituximab Combination Immunotherapy for
      Opsoclonus-Myoclonus Syndrome.
AB  - BACKGROUND: Rituximab (anti-CD20) has been used as B-cell-targeted intervention
      to treat opsoclonus-myoclonus syndrome. Due to isolated reports of chronic
      hypogammaglobulinemia and B lymphopenia following rituximab in several disorders,
      and rapid B-cell depletion after a few doses, we reduced the dosage 20% in our
      clinical practice. METHODS: In this Institutional Review Board-approved
      retrospective study, 32 children with opsoclonus-myoclonus syndrome and
      cerebrospinal fluid B-cell expansion had received front-loaded
      adrenocorticotropic hormone, intravenous immunoglobulin, and rituximab
      combination immunotherapy for de novo opsoclonus-myoclonus syndrome. Parametric
      statistical analysis compared 10 children receiving 1200 mg/m2 of rituximab (300
      mg/m2 * 4) and 22 receiving 1500 mg/m2 (375 mg/m2 * 4). Clinical response had
      been video documented and scored by a blinded observer. RESULTS: In both groups,
      motor severity (total score) lessened by >=76% and cerebrospinal fluid B cells
      were similarly depleted (>=95%) six months after treatment. None of the treated
      patients remained unable to walk independently. Serum IgM depletion was analogous
      in the 1200 mg/m2 (-73%) and 1500 mg/m2 group (-64%). The relapse frequency was
      similar in both groups. Side effects were principally steroidal, tolerable, and
      transient. Circulating B-cell repopulation was comparable. CONCLUSIONS: The
      reduced-dose of rituximab in rituximab combination immunotherapy was as effective
      and well tolerated as the standard dose, and provided rapid, early therapeutic
      intervention in opsoclonus-myoclonus syndrome. Pending a long-term prospective
      study, these are proof-of-concept data in support of challenging the dose of
      rituximab in various disorders, which may have different dose requirements.

PMID- 30197221
TI  - Juvenile Ocular Myasthenia Gravis: Presentation and Outcome of a Large Cohort.
AB  - BACKGROUND: Isolated ocular myasthenia gravis (MG) is sparingly common in
      children relative to adults, ranging from 71% to 93% of all children with MG.
      PURPOSE: We aimed to characterize the ocular manifestations and outcomes in
      children with isolated ocular MG. METHODS: Medical records of consecutive 62
      subjects less than 15 years of age with ocular MG, were retrospectively reviewed.
      Demographic data, presenting ocular features, types and variabilities of duction
      limitation, MG confirmatory tests, types of and responses to treatment, and
      generalized MG conversion were reviewed. RESULTS: Mean age at onset and follow-up
      time were 49 months (range, one to 173 months) and 95 months (range, six to 226
      months), respectively. Female-to-male ratio was 1.5:1. Initially, ptosis was
      found in 60 subjects (96.8%), while duction limitation was observed in 28
      subjects (45.2%). Total ophthalmoparesis was the most common type of duction
      limitation. Variability of duction limitation was found in 68% of subjects during
      the follow-up. Pyridostigmine alone was the most common medication used (48.4%);
      ptosis was more responsive to therapy than duction limitation. Conversion to
      generalized MG occurred in 19.4% of subjects, with a mean interval to conversion
      of nine months after symptom onset. Most conversions (91.7%) occurred in the
      first two years. CONCLUSIONS: Ptosis was more responsive to treatment than
      duction limitation. Thus other treatment modalities, as well as strabismic
      amblyopia screening, should be considered in children with prolonged duction
      limitation that is refractory to medication. In contrast with adults, a much
      lower proportion of children converted to generalized MG. This may explain the
      higher prevalence of isolated ocular MG among the juvenile population.

PMID- 30197222
TI  - Cryo-electron tomography for the structural study of mitochondrial translation.
AB  - Cryo-electron tomography (cryo-ET) enables the three-dimensional (3D) structural
      characterization of macromolecular complexes in their physiological environment.
      Thus, cryo-ET is uniquely suited to study the structural basis of biomolecular
      processes that are extremely difficult or even impossible to reconstitute using
      purified components. Translation of mitochondrial genes, which occurs in the
      secluded interior of mitochondria, falls into this category. Here, we describe
      the principles of cryo-ET in the context of mitochondrial translation and outline
      recent developments and challenges of the method. The 3D image of a frozen
      hydrated biological sample is computed from its 2D projections, which are
      acquired using a transmission electron microscope. In conjunction with automated
      detection of different copies of the molecule of interest and averaging of the
      corresponding subtomograms, cryo-ET enables macromolecular structure
      determination in the native environment (i.e. in situ) at sub-nanometer
      resolution. The preservation of the native environment furthermore allows the
      extraction of contextual information about the molecules, including the location
      of specific molecules with respect to membranes, their relative positioning and
      the spatial organization with respect to other types of macromolecules. Recent
      preparative developments extend the field of application of cryo-ET from isolated
      organelles to cultured eukaryotic cells and even tissue, making the traditional
      borders between molecular and cellular structural biology disappear.

PMID- 30197223
TI  - Social capital and disaster preparedness in Oromia, Ethiopia: An evaluation of
      the "Women Empowered" approach.
AB  - Ethiopia is faced with challenges posed by natural disasters, especially drought.
      Integrated approaches to disaster risk reduction are necessary to improve the
      lives and livelihoods of those most vulnerable to disaster. The Women Empowered
      (WE) approach provides economic and social opportunities for women to build
      resilience to respond to disasters. This study examines the association between
      WE group membership and disaster preparedness and whether this relationship is
      mediated by social capital. We used a multi-stage random cluster sampling
      strategy to select and interview 589 female respondents from Lage Hidha district
      (298 from the intervention area and 291 in the comparison area). Using Stata
      14.0, we employed Poisson regression analysis to study the mechanisms through
      which WE groups are associated with disaster preparedness. After controlling for
      clustering and confounding factors, we found that different components of social
      capital mediate the relationship between WE group membership and disaster
      preparedness. Specifically, taking action to prepare for a disaster is primarily
      mediated by emotional support from the group and perceived preparedness for a
      disaster is mediated by social network support, emotional support from the group,
      collective action, and trust. This study suggests that the association between WE
      groups and disaster preparedness operates through social capital in drought-prone
      areas of Ethiopia. Future research is needed to determine which forms of social
      capital have the greatest potential to help families prepare for and respond to a
      variety of humanitarian crises.

PMID- 30197224
TI  - Comparing static and dynamic predictors of risk for hostility in serious mental
      illness: Preliminary findings.
AB  - This study compared static predictors of hostility (e.g. demographics, clinician
      ratings) to subjective (i.e., self-reported affect on slider scales in response
      to written questions) and objective (i.e., vocal indicators of arousal from
      speech samples in a story-retelling task) dynamic predictors using ambulatory
      assessment over five days in a sample of 25 stable outpatients with diagnoses of
      a serious mental illness. Multilevel modeling showed that both subjective and
      objective dynamic predictors were significant, but none of the static predictors
      were. These results suggest that, in predicting hostility, it is more important
      to account for state variation than static traits.

PMID- 30197225
TI  - Smart Bandages: The Future of Wound Care.
AB  - Chronic non-healing wounds are major healthcare challenges that affect a
      noticeable number of people; they exert a severe financial burden and are the
      leading cause of limb amputation. Although chronic wounds are locked in a
      persisting inflamed state, they are dynamic and proper therapy requires
      identifying abnormalities, administering proper drugs and growth factors, and
      modulating the conditions of the environment. In this review article, we discuss
      technologies that have been developed to actively monitor the wound environment.
      We also highlight drug delivery tools that have been integrated with bandages to
      facilitate precise temporal and spatial control over drug release and review
      automated or semi-automated systems that can respond to the wound environment.

PMID- 30197226
TI  - Tongue function is important for masticatory performance in the healthy elderly:
      A cross-sectional survey of community-dwelling elderly.
AB  - PURPOSE: The aim of this study was to determine the influences of oral motor
      function such as tongue function and bite force on masticatory performance in the
      elderly. METHODS: We randomly selected 245 subjects who has 28 natural teeth
      among community-dwelling elderly. We evaluated masticatory performance using a
      gummy jelly, and also measured bite force, tongue muscle force, and the speed of
      tongue movement. RESULTS: We found that reduced masticatory performance to be
      associated with decreased the speed of tongue movement and/or tongue muscle
      force, indicating that reduced oral motor function also influences masticatory
      performance. CONCLUSIONS: These results suggest that keeping oral motor function,
      as well as maintenance of occlusal support, to be important for maintaining
      masticatory function in the elderly.

PMID- 30197227
TI  - Caring electronically for young outpatients who have epilepsy.
AB  - PURPOSE: The purpose of this study was to review electronic tools that might
      improve the delivery of epilepsy care, reduce medical care costs, and empower
      families to improve self-management capability. METHOD: We reviewed the epilepsy
      specific literature about self-management, electronic patient-reported or
      provider-reported outcomes, on-going remote surveillance, and alerting/warning
      systems. CONCLUSIONS: The improved care delivery system that we envision includes
      self-management, electronic patient (or provider)-reported outcomes, on-going
      remote surveillance, and alerting/warning systems. This system and variants have
      the potential to reduce seizure burden through improved management, keep children
      out of the emergency department and hospital, and even reduce the number of
      outpatient visits.

PMID- 30197229
TI  - Clozapine-induced myocarditis: A rare adverse drug reaction not to ignore.

PMID- 30197228
TI  - [Illogical association nalmefene and opioids: Analysis in the French
      pharmacovigilance database].
AB  - INTRODUCTION: Nalmefene, an opioid antagonist, causes withdrawal syndromes in
      patients exposed to an opioid agonist. Despite its contraindication, this
      illogical drug association persists, especially with opioid substitution drugs
      (ODS). We measured the benefits of the modification in the summary of product
      characteristics (SPC) in March 2015 and the package leaflet of Selincro(r) in
      September 2016 on this misuse. MATERIAL AND METHOD: We analyzed the observations
      regarding a use of nalmefene with an opioid between September 2014 and August
      2017 in the French pharmacovigilance database and the laboratory. RESULTS: The
      combination nalmefene and methadone was reported in about half of the cases
      (46/90). Observations were highest between October 2015 and March 2016 (29/90)
      and then decreased. Those with self-medication have increased. From October 2016,
      declarations become rarer. CONCLUSION: The effect of modifications in the SPC and
      the package leaflet on the use of nalmefene with ODS was real and progressive.

PMID- 30197230
TI  - Decompensation of adrenal insufficiency associated with birch juice use as stated
      by the manufacturer information leaflet: A case report.

PMID- 30197231
TI  - Thyroid storm following rapid sequence intubation.
AB  - Thyroid storm is a rare complication with an estimated incidence ranging from
      0.61 to 0.76 cases per 100,000 people. Common causes include intrinsic
      hyperthyroidism, such as in Grave's disease, infection, surgery, severe emotional
      stress, and acute trauma to the thyroid gland. Without immediate treatment,
      mortality is seen in up to 30% of cases. Here, we report a case of a 46-year-old
      male who presented with a possible food impaction for the past 48 h. The patient
      developed extreme hypertension, tachycardia, and diaphoresis immediately
      following rapid sequence intubation (RSI), which, after further work-up, was due
      to thyroid storm.

PMID- 30197232
TI  - Which technique for resuscitation physicians should use? Preliminary data.

PMID- 30197233
TI  - Use of the vestibular and oculomotor examination for concussion in a pediatric
      emergency department.
AB  - BACKGROUND: Concussion guidelines recommend a vestibular and oculomotor (VOM)
      examination be performed for all patients with concern for concussion, however
      the feasibility of performing testing is unknown. We aimed to measure rates of
      exam performance after implementation of training and support tools in a
      pediatric emergency department. METHODS: We conducted a retrospective study of
      patients age 6 to 18 years old presenting over a 12-month period. Charts were
      obtained via natural language processing, where concussion was suggested as a
      diagnosis in the electronic health record, and then manually reviewed to record
      patient and provider factors. A multivariable logistic regression was performed
      to determine factors associated with exam performance, and a classification and
      regression tree (CART) analysis was performed to determine if a specific patient
      type was at risk for not having testing performed. RESULTS: Four hundred patients
      were included in the analysis. Sixty-four percent received a VOM examination
      (including 73% of those diagnosed with concussion). Provider type, concussion
      history, symptom burden, injury mechanism, and final diagnosis were all
      significantly associated with exam performance. CART analysis determined patients
      with a non-concussion diagnosis, a non-sports injury mechanism, no prior history
      of concussion, and two or fewer symptoms had the lowest likelihood (46%) of
      receiving the exam. CONCLUSION: Performing a VOM examination for concussion is
      feasible in the acute setting following provider education and using clinical
      support tools. The exam is more likely to be performed on those children with
      history or exam findings associated with perceived risk for ongoing symptoms.

PMID- 30197234
TI  - Precise control of maxillary multidirectional movement in Le Fort I osteotomy
      using a surgical guiding device.
AB  - We introduced a surgical protocol to achieve accurate maxillary multidirectional
      movement in Le Fort I osteotomies. This comprised a way of controlling precision
      and a guiding device together with prebent titanium plates. We evaluated the
      protocol using a semiautomated 3-dimensional assessment in 22 patients with
      maxillary multidirectional movement (movement in three or more of six
      directions). Operations were all done between October 2015 and April 2017 by the
      same surgeon, who followed the protocol strictly. To evaluate the accuracy, we
      measured the deviation of the orientation of landmarks and of the upper
      dentition. All cases were followed up for at least a year. They all involved
      maxillary movement in at least three directions, and nine involved movement in
      six. The guiding device was used intraoperatively in all cases. Vertical
      deviation of the segments of bone was often detected during removal of bone, and
      sagittal deviation in three cases, but we found no transverse deviations. The
      assessment of accuracy showed that the mediolateral, anteroposterior, and
      superoinferior translations of landmarks were all less than 1mm, with mean values
      of 0.29, 0.43, and 0.39mm, respectively. The pitch, roll, and yaw of the upper
      dentition were also less than 1 degrees , with mean values of 0.60 degrees , 0.35
      degrees , 0.36 degrees , respectively. The proposed protocol allowed accurate
      reposition of the maxilla with multidirectional movement during Le Fort I
      osteotomy.

PMID- 30197235
TI  - Development of a position statement for Australian critical care nurse education.
AB  - Position statements are used by large organisations such as the Australian
      College of Critical Care Nurses to publically present an official philosophy or
      beliefs and to propose recommendations. Position statements are increasingly used
      by health departments and healthcare facilities to allocate resources and to
      guide and audit nursing practice, yet there are limited resources on the process
      of their development. A position statement should help readers better understand
      the issue, communicate solutions to problems, and inform decision-making. It
      should be supported by the highest level of evidence available and reflect the
      organisation's governing objectives and goals. In this article, we describe the
      structured approach used to develop a position statement for Australian critical
      care nurse education. The formation of an expert advisory panel, synthesis of
      available evidence using Whittemore and Knafl's integrative review methodology,
      use of Donabedian's structure-process-outcomes quality framework as a theoretical
      approach, and multiple layers of consensus building and consultation enabled the
      development of an important critical care document and informed an implementation
      plan. The framework and processes we have outlined in this discussion article may
      provide a useful starting point for other professional organisations wishing to
      develop similar position statements.

PMID- 30197236
TI  - Cadherin Combinations Recruit Dendrites of Distinct Retinal Neurons to a Shared
      Interneuronal Scaffold.
AB  - Distinct neuronal types connect in complex ways to generate functional neural
      circuits. The molecular diversity required to specify this connectivity could be
      supplied by multigene families of synaptic recognition molecules, but most
      studies to date have assessed just one or a few members at a time. Here, we
      analyze roles of cadherins (Cdhs) in formation of retinal circuits comprising
      eight neuronal types that inform the brain about motion in four directions. We
      show that at least 15 classical Cdhs are expressed by neurons in these circuits
      and at least 6 (Cdh6-10 and 18) act individually or in combinations to promote
      specific connectivity among the cells. They act in part by directing the
      processes of output neurons and excitatory interneurons to a cellular scaffold
      formed by inhibitory interneurons. Because Cdhs are expressed combinatorially by
      many central neurons, similar interactions could be involved in patterning
      circuits throughout the brain.

PMID- 30197238
TI  - Validation of a simplified in vitro Transwell(r) model of the alveolar surface to
      assess host immunity induced by different morphotypes of Aspergillus fumigatus.
AB  - Interactions between fungal pathogens such as Aspergillus fumigatus with host
      alveolar epithelium and innate immune cells are crucial in the defense against
      opportunistic fungal infections. In this study a simplified Transwell(r) system
      with a confluent layer of A549 cells acted as a model for the alveolar surface.
      A. fumigatus and dendritic cells were added to simulate the spatial and cellular
      complexity in the alveolus. Fungal growth into the lower chamber was validated by
      galactomannan assays. Addition of moDCs to the upper chamber led to a reduced GM
      signal and fungal growth, indicating moDC antifungal activity. Minimal cell death
      was documented by analyses of lactate dehydrogenase concentrations and pro
      apoptotic gene expression. Measurement of trans-epithelial dextran blue movement
      confirmed tightness of the epithelial barrier even in presence of A. fumigatus.
      Cytokine measurements in supernatants from both chambers of the Transwell(r)
      system documented distinct response patterns during early and late stages of
      epithelial invasion, with A549 cells appearing to make a minimal contribution to
      cytokine release. Concentrations of cytokines in the lower chamber varied
      distinctly from the upper chamber, depending on the molecular weight of the
      cytokines. Low inter-assay variability of fungal biomarkers and cytokines was
      confirmed, highlighting that in vitro models closely mimicking conditions in the
      human lung can facilitate reproducible measurement of the dynamics of cytokine
      release and fungal penetration of host epithelia.

PMID- 30197237
TI  - FoxO Function Is Essential for Maintenance of Autophagic Flux and Neuronal
      Morphogenesis in Adult Neurogenesis.
AB  - Autophagy is a conserved catabolic pathway with emerging functions in mammalian
      neurodevelopment and human neurodevelopmental diseases. The mechanisms
      controlling autophagy in neuronal development are not fully understood. Here, we
      found that conditional deletion of the Forkhead Box O transcription factors
      FoxO1, FoxO3, and FoxO4 strongly impaired autophagic flux in developing neurons
      of the adult mouse hippocampus. Moreover, FoxO deficiency led to altered
      dendritic morphology, increased spine density, and aberrant spine positioning in
      adult-generated neurons. Strikingly, pharmacological induction of autophagy was
      sufficient to correct abnormal dendrite and spine development of FoxO-deficient
      neurons. Collectively, these findings reveal a novel link between FoxO
      transcription factors, autophagic flux, and maturation of developing neurons.

PMID- 30197239
TI  - Myomaker and Myomerger Work Independently to Control Distinct Steps of Membrane
      Remodeling during Myoblast Fusion.
AB  - Classic mechanisms for membrane fusion involve transmembrane proteins that
      assemble into complexes and dynamically alter their conformation to bend
      membranes, leading to mixing of membrane lipids (hemifusion) and fusion pore
      formation. Myomaker and Myomerger govern myoblast fusion and muscle formation but
      are structurally divergent from traditional fusogenic proteins. Here, we show
      that Myomaker and Myomerger independently mediate distinct steps in the fusion
      pathway, where Myomaker is involved in membrane hemifusion and Myomerger is
      necessary for fusion pore formation. Mechanistically, we demonstrate that
      Myomerger is required on the cell surface where its ectodomains stress membranes.
      Moreover, we show that Myomerger drives fusion completion in a heterologous
      system independent of Myomaker and that a Myomaker-Myomerger physical interaction
      is not required for function. Collectively, our data identify a stepwise cell
      fusion mechanism in myoblasts where different proteins are delegated to perform
      unique membrane functions essential for membrane coalescence.

PMID- 30197240
TI  - Opposing Action of Hedgehog and Insulin Signaling Balances Proliferation and
      Autophagy to Determine Follicle Stem Cell Lifespan.
AB  - Egg production declines with age in many species, a process linked with stem cell
      loss. Diet-dependent signaling has emerged as critical for stem cell maintenance
      during aging. Follicle stem cells (FSCs) in the Drosophila ovary are exquisitely
      responsive to diet-induced signals including Hedgehog (Hh) and insulin-IGF
      signaling (IIS), entering quiescence in the absence of nutrients and initiating
      proliferation rapidly upon feeding. Although highly proliferative FSCs generally
      exhibit an extended lifespan, we find that constitutive Hh signaling drives FSC
      loss and premature sterility despite high proliferative rates. This occurs due to
      Hh-mediated induction of autophagy in FSCs via a Ptc-dependent, Smo-independent
      mechanism. Hh-dependent autophagy increases during aging, triggering FSC loss and
      consequent reproductive arrest. IIS is necessary and sufficient to suppress Hh
      induced autophagy, promoting a stable proliferative state. These results suggest
      that opposing action of diet-responsive IIS and Hh signals determine reproductive
      lifespan by modulating the proliferation-autophagy balance in FSCs during aging.

PMID- 30197242
TI  - Clinical Characteristics, Complications, and Treatment Practices in Patients With
      RHD: 6-Year Results From HP-RHD Registry.
AB  - BACKGROUND: Despite the high prevalence of rheumatic heart disease (RHD) in
      developing countries such as India, data on characteristics, complications, and
      treatment practices are lacking. The HP-RHD (Himachal Pradesh Rheumatic Heart
      Disease) registry aimed at reporting these parameters in patients with RHD from a
      northern state of India. METHODS: A total of 2,005 consecutive patients of RHD
      were enrolled over a period of 6 years (2011 to 2016) in the present study. The
      clinical characteristics, complications, and treatment practices were
      systematically recorded. RESULTS: The mean age for patients with RHD was 40.3 +/-
      14.3 (range 5 to 83 years). RHD predominantly affected females (72.3%) and
      population from rural background (92%). Multivalvular involvement was frequent
      (43.2%), mitral valve was the commonest affected valve (83.3%). The majority of
      the patients had moderate-to-severe valvular dysfunction (69.3%). Mitral and
      tricuspid valve involvement was more frequent in female subjects compared with
      more frequent aortic valve involvement in male subjects (p < 0.001). The major
      adverse cardiovascular events were recorded in 23.4% patients at the time of
      registry and comprised mainly advanced heart failure (15.6%), peripheral embolism
      (4.1%), and stroke (3.9%). The independent risk determinants of major adverse
      cardiovascular events (were advanced age (odds ratio [OR]: 1.01; 95% confidence
      interval [CI]: 1.00-1.02), severe mitral stenosis (OR: 1.73; 95% CI: 1.34-2.20),
      severe tricuspid regurgitation (OR: 2.11; 95% CI: 1.48-3.02), presence of
      pulmonary artery hypertension (OR: 1.33; 95% CI: 1.04-1.69), and atrial
      fibrillation (OR: 1.64; 95% CI: 1.28-2.11). Evidence-based use of oral
      anticoagulant therapy was documented in 77.7% of high-risk patients. Only 28.5%
      of study population was receiving secondary prophylaxis. CONCLUSIONS:
      Complications in patients with RHD increase with age and worsening valvular
      dysfunction. Programs focused on early detection and evidence-based management
      will assist in improving outcomes.

PMID- 30197241
TI  - Modulation of Asymmetric Division Diversity through Cytokinin and SPEECHLESS
      Regulatory Interactions in the Arabidopsis Stomatal Lineage.
AB  - Coordinated growth of organs requires communication among cells within and
      between tissues. In plants, leaf growth is largely dictated by the epidermis;
      here, asymmetric and self-renewing divisions of the stomatal lineage create two
      essential cell types-pavement cells and guard cells-in proportions reflecting
      inputs from local, systemic, and environmental cues. The transcription factor
      SPEECHLESS (SPCH) is the prime regulator of divisions, but whether and how it is
      influenced by external cues to provide flexible development is enigmatic. Here,
      we show that the phytohormone cytokinin (CK) can act as an endogenous signal to
      affect the extent and types of stomatal lineage divisions and forms a regulatory
      circuit with SPCH. Local domains of low CK signaling are created by SPCH
      dependent cell-type-specific activity of two repressive type-A ARABIDOPSIS
      RESPONSE REGULATORs (ARRs), ARR16 and ARR17, and two secreted peptides, CLE9 and
      CLE10, which, together with SPCH, can customize epidermal cell-type composition.

PMID- 30197243
TI  - Vasospastic angina: A literature review of current evidence.
AB  - Vasospastic angina (VSA) is a variant form of angina pectoris, in which angina
      occurs at rest, with transient electrocardiogram modifications and preserved
      exercise capacity. VSA can be involved in many clinical scenarios, such as stable
      angina, sudden cardiac death, acute coronary syndrome, arrhythmia or syncope.
      Coronary vasospasm is a heterogeneous phenomenon that can occur in patients with
      or without coronary atherosclerosis, can be focal or diffuse, and can affect
      epicardial or microvasculature coronary arteries. This disease remains
      underdiagnosed, and provocative tests are rarely performed. VSA diagnosis
      involves three considerations: classical clinical manifestations of VSA;
      documentation of myocardial ischaemia during spontaneous episodes; and
      demonstration of coronary artery spasm. The gold standard diagnostic approach
      uses invasive coronary angiography to directly image coronary spasm using
      acetylcholine, ergonovine or methylergonovine as the provocative stimulus.
      Lifestyle changes, avoidance of vasospastic agents and pharmacotherapy, such as
      calcium channel blockers, nitrates, statins, aspirin, alpha1-adrenergic receptor
      antagonists, rho-kinase inhibitors or nicorandil, could be proposed to patients
      with VSA. This review discusses the pathophysiology, clinical spectrum and
      management of VSA for clinicians, as well as diagnostic criteria and the
      provocative tests available for use by interventional cardiologists.

PMID- 30197244
TI  - Risk Factors for Local Relapse and Inferior Disease-free Survival After Breast
      conserving Management of Breast Cancer: Recursive Partitioning Analysis of 2161
      Patients.
AB  - BACKGROUND: The purpose of this study was to analyze risk factors for ipsilateral
      in-breast relapse and inferior disease-free survival (DFS) after standard
      adjuvant whole-breast radiotherapy (+/- boost and systemic treatment) as part of
      a multimodal breast-conserving approach. PATIENTS AND METHODS: Decision trees
      were built through recursive partitioning analysis (RPA). The median follow-up
      for all 2161 patients was 114 months (9.5 years). RESULTS: Local relapse in the
      treated breast was uncommon (actuarial rates after 5 and 10 years were 2.7% and
      5.8%, respectively). In RPA, the first split was related to age (52 years), with
      younger patients having a significantly higher risk of local relapse. The younger
      patients were stratified further by lymph node ratio (LNR). In patients older
      than 52 years, lack of endocrine treatment was associated with significantly
      higher risk. DFS was 80.7% at 10 years. The first split was caused by LNR, and
      the group with unfavorable LNR (> 0.20) could not be stratified further. Ten-year
      DFS in this group was as low as 50.6%. Patients with favorable LNR (0-0.20) could
      be stratified by additional risk factors, in particular primary tumor size.
      CONCLUSION: RPA is a suitable method to assign patients with early stage breast
      cancer to different risk groups, both regarding local relapse and DFS. Although
      age was a major risk factor for local relapse after breast-conserving management,
      LNR was associated with both endpoints. The systemic treatment approaches used in
      this study failed to provide satisfactory DFS in patients with LNR > 0.20 and 2
      other subgroups.

PMID- 30197245
TI  - Acute appendicitis: Factors associated with inconclusive ultrasound study and the
      need for additional computed tomography.
AB  - PURPOSE: To identify variables associated with inconclusive ultrasound
      examination and the need for further abdominopelvic computed tomography (CT)
      examination for the diagnosis of acute appendicitis. MATERIALS AND METHODS: A
      total of 105 adult patients with acute appendicitis were included. There were 55
      patients (38 men, 17 women; mean age, 23+/-9 [SD] years; range: 15-58 years) with
      a diagnosis of acute appendicitis using ultrasound alone and 50 patients (30 men,
      20 women; mean age, 31+/-14 [SD] years; range: 16-83 years) who required further
      CT. Demographic, clinical, and biological criteria and appendix location were
      compared between the two groups to search for variables associated with the need
      of further CT. RESULTS: Patients who required further CT were older (31.1+/-14
      [SD] years) and had a greater body mass index (BMI) (26.7+/-4.3 [SD]kg/m2) than
      those who did not require CT (23+/-9 [SD] years and 22.9+/-3.4 [SD]kg/m2),
      respectively (P<0.01). A greater proportion of patients with complicated acute
      appendicitis was observed in patients who required further CT (9/50; 18%) than in
      those who had only ultrasound (1/55; 2%) (P=0.012). Atypical appendix location
      was more frequent in patients who required CT (19/50; 36%) than in those who had
      only ultrasound (6/55; 11%) (P<0.001). There were no significant differences
      regarding gender, inflammatory syndrome and hours of imaging (on call vs. working
      hours) between the two groups. CONCLUSION: Advanced age, high BMI, atypical
      appendix location, and complicated appendicitis are associated with inconclusive
      ultrasound and the need for further CT to diagnose acute appendicitis.

PMID- 30197246
TI  - Migration of implanon contraceptive implant into the pulmonary artery.

PMID- 30197247
TI  - The 2018 ISHLT/APM/AST/ICCAC/STSW Recommendations for the Psychosocial Evaluation
      of Adult Cardiothoracic Transplant Candidates and Candidates for Long-term
      Mechanical Circulatory Support.
AB  - The psychosocial evaluation is well-recognized as an important component of the
      multifaceted assessment process to determine candidacy for heart transplantation,
      lung transplantation, and long-term mechanical circulatory support (MCS).
      However, there is no consensus-based set of recommendations for either the full
      range of psychosocial domains to be assessed during the evaluation, or the set of
      processes and procedures to be used to conduct the evaluation, report its
      findings, and monitor patients' receipt of and response to interventions for any
      problems identified. This document provides recommendations on both evaluation
      content and process. It represents a collaborative effort of the International
      Society for Heart and Lung Transplantation (ISHLT) and the Academy of
      Psychosomatic Medicine, American Society of Transplantation, International
      Consortium of Circulatory Assist Clinicians, and Society for Transplant Social
      Workers. The Nursing, Health Science and Allied Health Council of the ISHLT
      organized a Writing Committee composed of international experts representing the
      ISHLT and the collaborating societies. This Committee synthesized expert opinion
      and conducted a comprehensive literature review to support the psychosocial
      evaluation content and process recommendations that were developed. The
      recommendations are intended to dovetail with current ISHLT guidelines and
      consensus statements for the selection of candidates for cardiothoracic
      transplantation and MCS implantation. Moreover, the recommendations are designed
      to promote consistency across programs in the performance of the psychosocial
      evaluation by proposing a core set of content domains and processes that can be
      expanded as needed to meet programs' unique needs and goals.

PMID- 30197248
TI  - Small intestinal bacterial overgrowth is common after gastrectomy but with little
      impact on nutritional status.
AB  - BACKGROUND: Available evidence assessing the impact of small intestinal bacterial
      overgrowth (SIBO) following gastrectomy is limited. OBJECTIVES: To evaluate the
      prevalence of SIBO after gastrectomy and its association with malnutrition. To
      describe the antibiotic treatment required to correct it and if nutritional
      status improves. MATERIAL AND METHODS: A prospective cohort study was performed
      at the Agencia Sanitaria Costa del Sol (Costa del Sol Health Agency) from 2012 to
      2015. A hydrogen-methane breath test with oral glucose overload was performed.
      Demographic variables and nutritional parameters were collected at baseline and
      one month after effective treatment of SIBO. The antibiotic regimens and the
      number of treatment lines used were assessed. RESULTS: Sixty gastrectomy patients
      were analysed, 58.3% of which were male. A sub-analysis of the curve was
      performed at 45min to minimise possible false positives, and SIBO was identified
      in 61.6% of cases. SIBO patients tended to have a lower BMI, although this trend
      was not statistically significant. After treatment with rifaximin, 94.6% of
      patients were still positive for SIBO, which fell to 85.7% after metronidazole.
      The rate of total antibiotic treatment failure was 67.6%. No statistically
      significant changes were found in nutritional parameters after treatment.
      CONCLUSIONS: SIBO was identified in 61.6% of patients after gastrectomy. No
      correlation was found with any malnutrition parameter. Rifaximin and
      metronidazole were found to be largely ineffective in eradicating SIBO. When
      treatment was effective, the impact on malnutrition was negligible and may have
      been associated with other factors.

PMID- 30197249
TI  - Porous eco-friendly fibers for on-line micro solid-phase extraction of
      nonsteroidal anti-inflammatory drugs from urine and plasma samples.
AB  - In this study, cellulose acetate (CA) fibers were prepared using different
      solvent systems in electrospinning. The recorded scanning electron microscopy
      micrographs indicated that the morphology of the prepared fibers is closely
      associated with the type of electrospinning solvents. The prepared CA fibers were
      used as an extractive phase for on-line micro-solid phase extraction (MU-SPE) of
      nonsteroidal-inflammatory drugs (NSAIDs) in biological samples pursued by HPLC-UV
      determination. Work conducted on this research ascertained that the use of
      dichloromethane:acetone (3:1, v/v) solvent system in the CA dissolution for
      electrospinning, leads to the formation of porous ribbon-like fibers and
      subsequent excellent extraction efficiencies for the selected drugs. Moreover,
      the effects of diverse parameters on the extraction efficiency were surveyed and
      optimized. The proposed method was used for determination of naproxen, diclofenac
      and mefenamic acid in human urine and plasma samples. The optimized method was
      validated and the limits of detection (1.0-2.4 MUg L-1), limits of quantification
      (3.3-8.0 MUg L-1) and linear dynamic range (4.0-1000.0 MUg L-1) were obtained.
      The reproducibility (relative standard deviation: 2.6-7.9%) was in an acceptable
      range. Trueness of the procedure was accomplished through recovery assays in
      urine (94-105%) and plasma (85-102%) samples, indicating the minor contribution
      from the sample matrix. Finally, the CA porous fibers within the framework of the
      MU-SPE method were found to be appropriate for the separation and determination
      of the selected drugs in urine and plasma samples collected from treated
      patients. Also, the adsorption behavior of the porous fibers was well described
      by Freundlich isotherm and porous fibers showed acceptable adsorption capacity.

PMID- 30197251
TI  - Effects of prenatal education on complaints during pregnancy and on quality of
      life.
AB  - OBJECTIVE: The study was conducted to determine the effects of prenatal education
      on quality of life and complaints during pregnancy. METHODS: This study is a
      quasi-experimental research with a control group. Personal Information Form and
      Scale of Complaints during Pregnancy and their Effects on Quality of Life
      (SCPEQL) were used to collect the data. Thirty participants were included in both
      the control and the intervention groups (N = 60). RESULTS: The mean scores of
      SCPEQL of the intervention group was 46.2 +/- 21.1 and the mean scores of SCPEQL
      of the control group was 99.8 +/- 21.6 in 2nd trimester. In the 3rd trimester,
      the mean score of SCPEQL of the intervention group was 43.5 +/- 16.4, and the
      mean score of SCPEQL of the control group was 108.0 +/- 16.8. The difference
      between the groups was statistically significant in 2nd and 3rd trimesters (p <
      0.05). CONCLUSION: Findings of the study suggest that providing prenatal
      education reduces complaints and increases quality of life of pregnant women.
      PRACTICE IMPLICATIONS: Assessing complaints during pregnancy by nurses is a part
      of the prenatal care. Therefore, nurses should evaluate pregnancy-related
      complaints. Quality of life should be increased by giving effective education
      about complaints during pregnancy.

PMID- 30197250
TI  - Ultrafast separations via pulse flow valve modulation to enable high peak
      capacity multidimensional gas chromatography.
AB  - Ultrafast modulation with a modulation period PM >= 50ms via a pulse flow valve
      is demonstrated for comprehensive two-dimensional gas chromatography (GC*GC) and
      comprehensive three-dimensional (3D) gas chromatography (GC3). Significant
      increases in peak capacity and peak capacity production are achieved for GC*GC
      and GC3 relative to previous studies due to using pulse flow valve modulation.
      Due to the nature of the "partial" modulation process, the separation dimension
      following pulse flow valve modulation is not a traditional chromatogram, rather
      requires data processing to convert the data to expose the encoded
      chromatographic information, producing "apparent" chromatographic peaks. In the
      GC*GC mode, a 115-component test mixture was evaluated using a PM of 500ms,
      creating an apparent 2D peak width-at-base 2W with an average of 25ms, producing
      a 2nc of 20. Based on the average 1W of 1.0s for the 6min first dimension 1D
      separation, an ideal peak capacity nc,2D of 7200 is achieved (1,200/min peak
      production). For a high-speed GC*GC separation (30s run), a PM of 75ms produced
      apparent 2W of 8ms, ideal for the third dimension of a GC3 instrument. Using the
      knowledge gained from this high-speed GC*GC experiment, the pulse flow valve was
      implemented as the second modulator in GC3. Three samples were evaluated in the
      GC3 mode: a simple mixture containing 18 compounds (to illustrate basic
      concepts), the 115-component test mixture (to determine peak capacity figures-of
      merit), and a diesel spiked with 8 polar compounds (to illustrate chemical
      selectivity benefits of GC3). For the 115-component test mixture with a 1PM of
      1.2s and a 2PM of 60ms, average 1W of 3.2s, 2W of 130ms, and apparent 3W of 13ms
      were produced, resulting in a 1nc of 210, 2nc of 9.2, and 3nc of 5, respectively.
      Hence, an ideal peak capacity, nc,3D of ~10,000 for GC3 was achieved for the
      11min 1D separation window of the 115-component test mixture.

PMID- 30197252
TI  - The Taxonomy of Everyday Self-management Strategies (TEDSS): A framework derived
      from the literature and refined using empirical data.
AB  - OBJECTIVE: To extend our understanding of self-management by using original data
      and a recent concept analysis to propose a unifying framework for self-management
      strategies. METHODS: Longitudinal interview data with 117 people with
      neurological conditions were used to test a preliminary framework derived from
      the literature. Statements from the interviews were sorted according to the
      predefined categories of the preliminary framework to investigate the fit between
      the framework and the qualitative data. Data on frequencies of strategies
      complemented the qualitative analysis. RESULTS: The Taxonomy of Every Day Self
      management Strategies (TEDSS) Framework includes five Goal-oriented Domains
      (Internal, Social Interaction, Activities, Health Behaviour and Disease
      Controlling), and two additional Support-oriented Domains (Process and Resource).
      The Support-oriented Domain strategies (such as information seeking and health
      navigation) are not, in and of themselves, goal focused. Instead, they underlie
      and support the Goal-oriented Domain strategies. Together, the seven domains
      create a comprehensive and unified framework for understanding how people with
      neurological conditions self-manage all aspects of everyday life. CONCLUSIONS:
      The resulting TEDSS Framework provides a taxonomy that has potential to resolve
      conceptual confusion within the field of self-management science. PRACTICE
      IMPLICATIONS: The TEDSS Framework may help to guide health service delivery and
      research.

PMID- 30197253
TI  - Arthroscopic Grading of Injuries of the Inferior Tibiofibular Syndesmosis.
AB  - The objective of this study was to describe the technical details of performing a
      newly developed arthroscopic grading of inferior tibiofibular syndesmosis
      injuries. Arthroscopy is emerging as the gold standard for evaluating painful,
      unstable ankles. The inferior tibiofibular syndesmosis contributes substantially
      to disorders of the ankle. However, no structured grading system exists that
      would help surgeons evaluate injuries of the syndesmosis. Seventy-eight patients
      with pain or instability symptoms in the ankle were arthroscopically evaluated
      for syndesmosis injury. The lesions were graded according to the prospectively
      developed protocol. More than 61% of the patients had syndesmosis disruptions of
      various grades affecting the anterior/posterior ligaments or both ligaments.
      Fourteen patients had anterior ligament disruptions whereas 4 patients had
      posterior lesions; another 7 patients had both ligaments asymmetrically injured.
      Eighteen of the 78 patients had symmetric grade 1 lesions, and 5 had grade 2
      lesions. More than half of chronic ankle pain cases have syndesmotic lesions.
      Symmetrical lesions of the anterior and posterior ligaments predominate, followed
      by isolated anterior ligament disruptions. The proposed grading system for
      inferior tibiofibular syndesmosis disruptions serves as a guide to systematic
      documentation of injuries of the syndesmosis.

PMID- 30197254
TI  - Predictors for Surgery-Related Emergency Department Visits within 30 Days of Foot
      and Ankle Surgeries.
AB  - Presentation to an emergency department (ED) after foot and ankle surgeries not
      only causes inconvenience to patients but also increases healthcare costs. To
      minimize this, many major institutions have tracked these data as a part of
      quality improvement measures. Our previous study showed that factors associated
      with any (surgery-related and unrelated) postoperative ED visits were not easily
      modifiable by surgeons. Therefore, in the current study, we focused on factors
      associated specifically with surgery-related postoperative ED visits, because
      this may provide some insights for surgeons rather than just administrators. We
      examined 513 foot and ankle surgeries, of which 114 resulted in 30-day
      postoperative ED visits for surgery-related reasons. Demographic, medical, and
      surgical factors were evaluated, and risk factors were identified after adjusting
      for potential clinically relevant covariates. Both inpatient and outpatient
      surgical settings and outpatient surgical settings alone were analyzed
      separately. Regardless of the setting, we found that shorter surgery was
      protective against postoperative ED visits, as was having a previous ED visit
      within 6 months before surgery. In the outpatient setting, younger age and having
      no insurance were also proxies for a postoperative ED visit, in addition to the
      above factors.

PMID- 30197255
TI  - Three-Dimensional Computed Tomographic Characterization of Normal Anatomic
      Morphology and Variations of the Distal Tibiofibular Syndesmosis.
AB  - Malreduction of distal tibiofibular syndesmosis (DTFS) leads to poor functional
      outcomes after ankle fracture surgery. Difficulty achieving anatomic alignment of
      the syndesmosis is due to variable morphology of the fibular incisura of the
      tibia and a paucity of literature regarding its morphologic characteristics. We
      surveyed 775 consecutive ankle computed tomography (CT) scans performed from June
      2008 to December 2011, and 203 (26.2%) were included for evaluation. Two
      observers performed quantitative measurements and qualitative evaluated fibular
      incisura morphology. Tang ratios for fibular rotation, anterior and posterior
      tibiofibular distances, fibular incisura depth, and subjective morphologies on CT
      were assessed using conventional multiplanar reconstruction (MPR) and maximum
      intensity projections (MIPs). On conventional CT, the mean Tang ratio was 0.97 +/
      0.06; the mean anterior tibiofibular distance was 2.17 +/- 0.87 mm; the mean
      posterior tibiofibular distance was 3.52 +/- 0.94 mm; and the mean depth of
      fibular incisura was 3.29 +/- 1.19 mm. Five morphologic variations of the fibular
      incisura were identified: crescentic, trapezoid, flat, chevron, and widow's peak.
      The most common fibular incisura morphology was crescentic (61.3%), followed by
      trapezoid shape (25.1%); the least common morphology was flat (3.1%).
      Interobserver variability with intraclass correlation coefficient (ICC) was
      slightly higher for all quantitative measures on MPR (ICC = 0.72 to .81) versus
      MIP (ICC = 0.64 to 0.75). ICC for incisura shape and depth assessments was poor
      on both modalities (0.13 to 0.38). This comprehensive CT study reports on
      quantitative and qualitative descriptive measures to evaluate fibular incisura
      morphologies and fibular orientation. It also defines the frequency of DTFS
      measures and the interobserver performance on 2 CT evaluation methods.

PMID- 30197256
TI  - Evaluation of the Mechanical Axis of the First Ray Before and After First
      Metatarsal-Phalangeal Joint Reconstructive Surgery.
AB  - LaPorta et al published a description of measurement of the mechanical axis of
      the first ray in an attempt to introduce center-of-rotation angulation principles
      into forefoot reconstructive surgery. They found significant differences in the
      measurement of the first intermetatarsal angle between groups of feet with and
      without hallux abducto valgus deformity, but they found no difference in the
      measurement of the M1-M2 mechanical axis angle between groups. The objectives of
      this study were to further investigate the proposed M1-M2 mechanical axis angle
      and to examine the effect of hallux abducto valgus corrective surgery on its
      measurement. We retrospectively evaluated weight-bearing dorsal-plantar
      projection radiographs taken in the angle and base of gait of 56 consecutive feet
      before and after first metatarsal-phalangeal joint corrective surgery. On each
      radiograph, we calculated the first intermetatarsal angle, the hallux abductus
      angle, the tibial sesamoid position, the M1-M2 mechanical axis angle, and the
      position of the sesamoids relative to the mechanical axis of the medial column.
      Statistically significant decreases were observed when comparing pre- versus post
      operative measurement of the first intermetatarsal angle (-4.83 degrees ; p <
      .001), hallux abductus angle (-11.46 degrees ; p < .001), and tibial sesamoid
      position (-1.99 positional grade; p < .001). Statistically significant
      differences were also observed for the M1-M2 mechanical axis angle (-0.47 degrees
      ; p = .007) and the position of the sesamoids relative to the mechanical axis of
      the medial column (0.38 positional grade; p < .001), but it is unlikely that
      these results would be considered clinically significant given the differences of
      less than 1 degrees  and less than 1 positional grade, respectfully. The results
      of this investigation add to the body of knowledge and will hopefully lead to
      future investigations into the progression, evaluation, and treatment of the
      hallux abducto valgus deformity.

PMID- 30197257
TI  - Quality Improvement Standards for the Treatment of Pediatric Empyema.

PMID- 30197258
TI  - Factors That Prevent Progression to Transcatheter Aortic Valve Implantation
      (TAVI).
AB  - BACKGROUND: Transcatheter aortic valve implantation (TAVI) is increasingly used
      for intermediate- and high-risk patients with severe symptomatic aortic stenosis
      (AS). However, safe undertaking of the procedure may be precluded by various
      anatomic factors. This study sought to identify prevalence of factors that
      prevent progression to TAVI. METHODS: TAVI candidates with severe AS undergoing
      workup coronary angiography and iliac vessel angiography (+/-cardiac-gated CT)
      were identified and factors precluding TAVI were reviewed retrospectively from a
      single-centre cardiac database over a 10-year period. RESULTS: 197 patients were
      included; mean age was 81.5+/-6.5years (+/-SD); 46.2% were male. 26.9% of TAVI
      candidates could not proceed to femoral access TAVI due to various factors
      including unsuitable peripheral vasculature (13.2%), untreated coronary artery
      disease (CAD) deemed high risk for TAVI (8.1%), unfavourable aortic
      characteristics (4.1%), and low-lying coronary ostia (1.5%). Factors associated
      with unsuitable femoral vasculature included female gender (p<0.01) and any CAD
      (p=0.03). Factors associated with the presence of unrevascularised CAD included
      male gender (p<0.01), estimated glomerular filtration rate (eGFR)<30mL/min/1.73m2
      (p=0.02), history of CAD (p<0.01), while prior percutaneous coronary intervention
      (PCI) or bypass surgery were protective (both p<0.01). Rates of progression to
      TAVI have increased over the last 10 years (p<0.01) from 58.3% prior to 2012 to
      83.7% in 2016 and 2017, while incidence of unsuitable peripheral vasculature
      preventing TAVI (p=0.01) and CAD deemed unsuitable for TAVI (p=0.04) have both
      decreased. CONCLUSIONS: Non-progression to TAVI among higher risk patients with
      severe AS has become less common over the last 10 years with improvements in
      operator experience, lower profile devices, and wider ranges of valve sizes.

PMID- 30197259
TI  - Incidence, Risk Factors, and Effect on Survival of Immune-related Adverse Events
      in Patients With Non-Small-cell Lung Cancer.
AB  - BACKGROUND: The risk factors for immune-related adverse events (irAEs) remain
      undefined. Recently, a correlation between irAEs and clinical benefit was
      suggested. We examined the risk factors for irAEs and their effect on survival in
      patients with non-small-cell lung cancer (NSCLC) who had received immunotherapy.
      PATIENTS AND METHODS: We performed a retrospective review of patients with NSCLC
      treated with single-agent immunotherapy at our institution. irAEs were determined
      by treating physician diagnosis. A landmark analysis was performed at 3 months
      using log-rank tests and the Bonferroni method. RESULTS: irAEs occurred in 27 of
      91 patients (30%). The median overall survival (OS) for patients with irAEs was
      longer than that for patients without (24.3 vs. 5.3 months; hazard ratio, 2.75;
      95% confidence interval, 1.54-4.92; P < .001). However, a landmark analysis of
      patients after 3 months of treatment revealed no difference in OS between
      patients with and without irAEs. No increased risk of pneumonitis was seen in
      patients with previous thoracic radiotherapy, although these patients had shorter
      survival (4.2 vs. 9.7 months; P = .004). Radiotherapy after the initiation of
      immunotherapy (n = 15) did not increase the risk of irAEs or pneumonitis;
      however, these patients had improved OS (17.3 vs. 6.0 months; P = .016).
      CONCLUSION: The development of irAEs did not significantly correlate with
      survival when controlling for the duration of therapy in a landmark analysis. We
      found no increased risk of pneumonitis or irAEs in patients who had received
      radiotherapy. Radiotherapy before immunotherapy was associated with shorter
      survival, and radiotherapy after immunotherapy was associated with improved
      survival.

PMID- 30197260
TI  - Bronchoscopic Manifestations of Airway Toxicity After Radiotherapy.

PMID- 30197262
TI  - PD-1 and PD-L1 Protein Expression Predict Survival in Completely Resected Lung
      Adenocarcinoma.
AB  - BACKGROUND: We assessed the prognostic value of programmed cell death 1 (PD-1)
      and programmed cell death ligand 1 (PD-L1) in patients with completely resected
      lung adenocarcinoma. PATIENTS AND METHODS: PD-1 and PD-L1 expression was
      determined using immunohistochemistry in formalin-fixed paraffin-embedded
      surgical specimens and correlated with the clinicopathologic features and
      survival of 161 patients with lung adenocarcinoma. RESULTS: PD-1 expression on
      immune cells was observed in 71 of 159 evaluable tumor samples (45%) and was not
      significantly associated with the clinicopathologic features. Multivariate
      analyses identified PD-1 expression as an independent prognostic factor for
      recurrence (adjusted hazard ratio [HR], 0.59; 95% confidence interval [CI], 0.36
      0.95; P = .03) and death (adjusted HR, 0.48; 95% CI, 0.27-0.86; P = 0.01). PD-L1
      expression on tumor cells was seen in 59 of 161 cases (37%) and correlated with
      KRAS mutation status (P = .02) and type of surgery (P = .01). PD-L1 expression
      was not associated with recurrence-free survival in the patients (adjusted HR,
      0.90; 95% CI, 0.55-1.48; P = .68) but correlated with longer overall survival
      (adjusted HR, 0.54; 95% CI, 0.30-0.97; P = .04). CONCLUSION: PD-1 and PD-L1
      expression was associated with favorable overall survival in patients with
      completely resected adenocarcinoma of the lung.

PMID- 30197261
TI  - First-line Chemotherapy Responsiveness and Patterns of Metastatic Spread Identify
      Clinical Syndromes Present Within Advanced KRAS Mutant Non-Small-cell Lung Cancer
      With Different Prognostic Significance.
AB  - BACKGROUND: Unsuccessful KRAS-specific treatment approaches in non-small-cell
      lung cancer (NSCLC) might reflect underlying disease heterogeneity. We sought to
      define clinical "syndromes" within advanced KRAS mutant NSCLC to improve future
      clinical trials and create a clinical framework for future molecular development.
      PATIENTS AND METHODS: To test a series of a priori hypotheses regarding KRAS
      mutant NSCLC clinical syndromes, we conducted a multi-institutional retrospective
      medical record review. Survival probabilities were estimated using the Kaplan
      Meier model. Between-group differences were assessed using the log-rank test.
      Multivariate Cox regression analyses and Wilcoxon rank sum testing were used to
      assess progression-free survival and overall survival (OS) differences. RESULTS:
      Among 218 patients with advanced KRAS-mutant NSCLC, OS and progression-free
      survival with first-line chemotherapy did not differ by intrathoracic versus
      extrathoracic spread, smoking intensity, or the specific KRAS mutation.
      Metastatic disease at diagnosis resulted in significantly worse OS than
      recurrent, unresectable disease (median OS, 14.6 vs. 40.9 months; P = .001).
      Among the patients with metastatic disease at diagnosis, nonscalp, soft tissue
      metastases (syndrome X; 6% of cases; 95% confidence interval [CI], 2.5%-10.1%)
      signified a poor prognosis (median OS, 7.5 vs. 15.9 months for the controls; P =
      .021). The response to first-line chemotherapy (syndrome Y; 41% of cases; 95% CI,
      32.3%-50.6%) signified a good prognosis (median OS, 26.7 vs. 11.9 months; P =
      .002). The overlap between these 2 syndromes was minimal (2 of 111). Multivariate
      analysis confirmed these observations. The hazard ratio for death for syndromes X
      and Y was 2.64 (95% CI, 1.13-6.14) and 0.45 (95% CI, 0.28-0.76), respectively.
      CONCLUSION: Chemotherapy-responsive disease and nonscalp, soft tissue spread
      might represent distinct clinical syndromes within KRAS-mutant NSCLC. The
      molecular biology underlying this heterogeneity warrants future studies.

PMID- 30197263
TI  - Twice-daily Thoracic Radiotherapy for Limited-stage Small-cell Lung Cancer Does
      Not Increase the Incidence of Acute Severe Esophagitis.
AB  - PURPOSE: Acute esophagitis is common after thoracic radiation therapy (TRT) given
      with chemotherapy for limited-stage small-cell lung cancer (LS SCLC). Although
      twice-daily TRT to 45 Gy in 30 fractions is considered standard, some clinicians
      are reluctant to use this schedule because of its perceived impracticality and
      risk of severe esophagitis. We reviewed a single-institution experience with
      severe (grade >= 3) esophagitis after TRT with chemotherapy for LS SCLC. PATIENTS
      AND METHODS: A total of 504 patients were identified as having received TRT (>=45
      Gy) with platinum-containing chemotherapy for LS SCLC at MD Anderson Cancer
      Center in 1987 through 2012. Patients with complete or good partial response were
      offered prophylactic cranial irradiation. Esophagitis was scored retrospectively
      with the Common Terminology Criteria for Adverse Events, V3.0. Clinical variables
      were analyzed for possible association with acute grade >= 3 esophagitis.
      RESULTS: At a median follow-up time of 23.9 months (range, 1.2-240.8 months), 103
      (20%) patients had experienced grade >= 3 esophagitis. In univariate analysis,
      TRT dose >= 60 Gy was the only factor associated with severe esophagitis (odds
      ratio [OR], 1.84; 95% confidence interval [CI], 1.02-3.30; P = .043); use of
      twice-daily TRT was not (OR, 0.96; 95% CI, 0.61-1.52; P = .867). The significance
      of TRT to >= 60 Gy was maintained in multivariate Cox regression analysis
      adjusted for tumor size (OR, 1.91; 95% CI, 1.05-3.46; P = .034). CONCLUSIONS: TRT
      to >= 60 Gy predicted acute severe esophagitis, but twice-daily fractionation did
      not. Standard-dose 45-Gy twice-daily TRT should not be avoided for fear of severe
      esophagitis.

PMID- 30197264
TI  - Osimertinib With Ramucirumab in EGFR-mutated, T790M-positive Patients With
      Progression During EGFR-TKI Therapy: Phase Ib Study.
AB  - BACKGROUND: Epidermal growth factor receptor (EGFR) T790M mutation is the most
      frequent mechanism of resistance among patients with progression during EGFR
      tyrosine kinase inhibitor (TKI) therapy. A third-generation EGFR-TKI,
      osimertinib, demonstrated durable efficacy with mild adverse events in a phase
      III trial and is considered a novel standard regimen. The tolerability of
      osimertinib monotherapy has allowed for the development of a more efficacious
      combination regimen. Preclinical and clinical study data have suggested that
      vascular endothelial growth factor inhibition can enhance EGFR-TKI activity with
      tolerable toxicity. AIMS: The aim of the present single-arm, phase Ib study is to
      assess the tolerability of osimertinib combined with ramucirumab in patients with
      EGFR-mutated, T790M+ lung cancer with progression during EGFR-TKI therapy. The
      primary endpoint is to assess the safety of osimertinib plus ramucirumab at a
      fixed dose. The secondary endpoints are the overall response rate, progression
      free survival, overall survival, and safety. Six patients will be enrolled in the
      trial.

PMID- 30197265
TI  - Phase III Randomized Trial of Palonosetron and Dexamethasone With or Without
      Aprepitant to Prevent Nausea and Vomiting Induced by Full-dose Single-day
      Cisplatin-based Chemotherapy in Lung Cancer.
AB  - INTRODUCTION: This study aimed to determine the efficacy and safety of
      aprepitant, palonosetron, and dexamethasone to prevent chemotherapy-induced
      nausea and vomiting in patients with locally advanced or metastatic lung cancer
      receiving full-dose single-day cisplatin-based combination chemotherapy.
      MATERIALS AND METHODS: Patients diagnosed with locally advanced or metastatic
      lung cancer who received full dose single-day cisplatin-based chemotherapy were
      randomized (1:1) to aprepitant plus palonosetron and dexamethasone, or placebo
      plus palonosetron and dexamethasone. The primary endpoint was complete response
      of nausea and vomiting in the first cycle. The secondary endpoints were the
      proportion of patients with nausea and vomiting who received rescue antiemetic
      medication, the response of cross-over patients, and safety. RESULTS: A total of
      244 patients were randomized. There was no difference between the 2 groups
      regarding personal characteristics. The administration of aprepitant
      significantly improved the complete response for vomiting in the overall period
      (92.6% vs. 79.93%; P < .01), but not a nausea-free response (75.4% vs. 71.3%; P >
      .05) in the first cycle. The percentage of patients who received rescue
      antiemetic medication was decreased for the aprepitant group (14.8% vs. 37.1%; P
      < .001). Patients who did not use aprepitant and suffered with nausea and
      vomiting in cycle 1 were crossed over to the aprepitant group (N = 32), and the
      rate of nausea and vomiting in cycle 2 was decreased to 37.5% (P < .05) and 25%
      (P < .05), respectively. There were no drug-related adverse effects. CONCLUSIONS:
      Aprepitant plus palonosetron and dexamethasone proved to be effective and well
      tolerated in preventing chemotherapy-induced nausea and vomiting after
      administration of full-dose single-day cisplatin-based combination chemotherapy.

PMID- 30197266
TI  - Self-reported vaccination coverage against tick-borne encephalitis in Slovenia.

PMID- 30197267
TI  - Multi-locus sequence typing of Ixodes ricinus and its symbiont Candidatus
      Midichloria mitochondrii across Europe reveals evidence of local co-cladogenesis
      in Scotland.
AB  - Ticks have relatively complex microbiomes, but only a small proportion of the
      bacterial symbionts recorded from ticks are vertically transmitted. Moreover, co
      cladogenesis between ticks and their symbionts, indicating an intimate
      relationship over evolutionary history driven by a mutualistic association, is
      the exception rather than the rule. One of the most widespread tick symbionts is
      Candidatus Midichloria, which has been detected in all of the major tick genera
      of medical and veterinary importance. In some species of Ixodes, such as the
      sheep tick Ixodes ricinus (infected with Candidatus Midichloria mitochondrii),
      the symbiont is fixed in wild adult female ticks, suggesting an obligate
      mutualism. However, almost no information is available on genetic variation in
      Candidatus M. mitochondrii or possible co-cladogenesis with its host across its
      geographic range. Here, we report the first survey of Candidatus M. mitochondrii
      in I. ricinus in Great Britain and a multi-locus sequence typing (MLST) analysis
      of tick and symbiont between British ticks and those collected in continental
      Europe. We show that while the prevalence of the symbiont in nymphs collected in
      England is similar to that reported from the continent, a higher prevalence in
      nymphs and adult males is apparent in Wales. In general, Candidatus M.
      mitochondrii exhibits very low levels of sequence diversity, although a
      consistent signal of host-symbiont coevolution was apparent in Scotland.
      Moreover, the tick MLST scheme revealed that Scottish specimens form a clade that
      is partially separated from other British ticks, with almost no contribution of
      continental sequence types in this north-westerly border of the tick's natural
      range. The low diversity of Candidatus M. mitochondrii, in contrast with
      previously reported high rates of polymorphism in I. ricinus mitogenomes,
      suggests that the symbiont may have swept across Europe recently via a
      horizontal, rather than vertical, transmission route.

PMID- 30197268
TI  - Cost-effectiveness of a potential anti-tick vaccine with combined protection
      against Lyme borreliosis and tick-borne encephalitis in Slovenia.
AB  - This study assessed cost-effectiveness of a potential anti-tick vaccine that
      would protect against both Lyme borreliosis (LB) and tick-borne encephalitis
      (TBE) in a highly endemic setting of Slovenia. A Markov model was developed to
      estimate cost-effectiveness of a vaccine with potential combined protection
      against LB and TBE from the societal perspective. The model expressed time in
      annual cycles, followed a target population through their lifetime, and applied
      an annual discounting of 3%. A target population entered the model in a
      susceptible state, with time dependent probabilities to acquire LB/TBE. Disease
      manifestations were either resolved within one cycle, or a patient developed
      LB/TBE sequelae. The vaccination consisted of initial immunization and one
      revaccination. Estimates of LB/TBE direct and indirect costs, and data on natural
      course of LB/TBE were obtained from Slovenian databases. Effectiveness of the
      vaccine with potential combined protection against LB/TBE was derived from
      studies on existing TBE and LB vaccines, while utility estimates were collected
      from various literature sources. A vaccine with potential combined protection
      against LB/TBE was predicted to have an incremental cost of ?771,300 per 10,000
      vaccinated persons, an incremental utility of 17QALYs and a base-case incremental
      cost-effectiveness ratio (ICER) of 46,061?/QALY. Vaccine cost, effectiveness and
      discount rates were identified as the most influential model parameters. A
      wholesale price for a vaccine shot of ?9.13 would lead to cost savings followed
      by health gains for the vaccination strategy. The base-case ICER was below
      commonly accepted thresholds of cost-effectiveness, indicating that a combined
      LB/TBE vaccine might be a cost-effective option in Slovenia. With early Health
      Technology Assessment becoming increasingly important, this analysis still
      represents a rare example of cost-effectiveness assessment prior to market
      authorisation. Although obviously in such a situation some key parameters are
      unknown, our model sets up a tool to analyse pharmacoeconomic criteria that can
      help development of a cost-effective health technology, in this case a combined
      tick-borne diseases vaccine.

PMID- 30197269
TI  - Mediterranean spotted fever rickettsiosis in Italy, 2001-2015: Spatio-temporal
      distribution based on hospitalization records.
AB  - The Mediterranean spotted fever (MSF) rickettsiosis is the predominant
      rickettsial disease among the spotted fever group (SFG) rickettsiae in the
      Mediterranean countries and North Africa. Its causative agent is Rickettsia
      conorii, although, SFG rickettsiosis - cases due to Rickettsia monacensis,
      Rickettsia massiliae and Rickettsia aeschlimannii were also described. A
      retrospective study based on hospital discharge records with a diagnosis of SFG
      rickettsiosis was carried out to describe the spatial pattern, the trend of the
      disease, and the epidemiological characteristics of persons hospitalized in the
      period 2001-2015. Standardized hospitalization ratios were calculated at
      municipal level using the European population. Smoothed maps were produced using
      a localised smoothing Poisson model. The mean annual standardized hospitalization
      rate was 1.36/100,000 person years (95%CI: 1.34; 1.39). Rates showed strong
      summer seasonality and tended to decrease over time. During the study period,
      28.89% of municipalities had smoothed standardized hospitalization ratios greater
      than 1 and 14.01% above 20. Higher standardized hospitalization ratios were found
      in areas along the Tyrrhenian coast, especially in the south of Calabria and in
      the islands of Sardinia and Sicily, where the disease is of public health
      relevance.

PMID- 30197270
TI  - [Evaluation of the quality of recovery and the postoperative health status after
      elective surgery].
AB  - PURPOSE: Postoperative recovery is a complex process with physiologic,
      functional, and psychologic dimensions. Postoperative quality of recovery is
      considered as a crucial outcome following surgery and anesthesia. The objective
      of this study was to assess and compare the quality of postoperative recovery and
      health status before and after surgery, in patients undergoing elective surgery.
      METHODS: This observational, prospective study was conducted on patients proposed
      for elective surgery. Evaluation of postoperative recovery was performed using
      the Postoperative Quality of Recovery Scale and health status was assessed by
      applying the EuroQol assessing problems in five dimensions: mobility, personal
      care, usual activities, pain/discomfort, and anxiety/depression, and the World
      Health Organization Disability Assessment Schedule 2.0. Poor quality of recovery
      was defined as recovery in fewer than two domains at postoperative Day 1 in the
      Postoperative Quality of Recovery Scale. RESULTS: Before surgery (D0), patients
      with poor quality of recovery had median Visual Analog Scale scores in EuroQol
      similar to those of patients without poor quality of recovery, but they had more
      problems in the mobility, usual activities, pain/discomfort, and
      anxiety/depression dimensions. At 3 months after surgery, patients with poor
      quality of recovery had median Visual Analog Scale scores in EuroQol similar to
      those of patients without poor quality of recovery, but they maintained more
      problems in the pain/discomfort dimension. Patients with poor quality of recovery
      scored significantly higher on the World Health Organization Disability
      Assessment Schedule 2.0 scale at baseline, although the results were similar at 3
      months. CONCLUSIONS: Patients with poor quality of recovery had the worst health
      status at D0. Evaluation at 3 months indicated similar rates of problems in
      EuroQol (except for pain/discomfort) and World Health Organization Disability
      Assessment Schedule 2.0 scores were similar.

PMID- 30197272
TI  - Agitation and Aggression Are 2 Different Syndromes in Persons With Dementia.

PMID- 30197271
TI  - Tolerability and safety of early enteral nutrition in children after percutaneous
      endoscopic gastrostomy placement: A multicentre randomised controlled trial.
AB  - BACKGROUND & AIMS: We assessed the tolerability and safety of implementing early
      enteral nutrition in children at 3 h after percutaneous endoscopic gastrostomy
      (PEG) placement to establish an optimum feeding mode in paediatric patients that
      reduced the fasting period, the inadequate nutritional support interval, and the
      hospitalisation time. METHODS: Children with clinical indications for PEG
      placement were recruited from six medical centres in Poland to participate in the
      study. The patients were centrally randomised to receive the first bolus feed,
      which comprised a polymeric diet (1 kcal/mL), via a feeding tube at 3 h (group 1)
      or 8 h (group 2) after PEG placement. The pre-procedural preparation, the post
      operative care, and the resumption of feeding were performed on all of the
      patients in accordance with the study's protocol. The primary endpoint was the
      number of patients who consumed a full feed, which contained their total fluid
      and caloric requirements, within 48 h of the first bolus feed. The secondary
      endpoints were the number of complications and the duration of hospitalisation
      after PEG placement. RESULTS: Of the 97 randomised patients, 49 were assigned to
      group 1 and 48 were assigned to group 2. There were no differences between the
      groups regarding feeding tolerability (81.6% vs. 91.6%), the number of
      complications (25.5% vs. 37.5%), or the duration of hospitalisation after PEG
      placement (p > 0.05). Full feed post PEG placement was achieved within 24-48 h in
      most cases (74% vs. 82%). Most of the complications were mild. Two patients in
      group 2 due to dislocation of the PEG were qualified for laparotomy (at 6 days
      post-PEG placement in one case and at 14 days post-PEG placement in the other
      case). One patient in group 2 died at 7 days post-PEG placement; the death was
      unrelated to the investigation. CONCLUSIONS: Introducing feeding at 3 h post-PEG
      placement in children appears to be well tolerated. The early initiation of post
      PEG feeding was not associated with an increase in the number of complications
      and it had no impact on the duration of hospitalisation. CLINICAL TRIAL REGISTRY:
      www.clinicaltrials.gov (NCT02777541; registration date: 18/05/2016).

PMID- 30197273
TI  - Effects of free omega-3 carboxylic acids and fenofibrate on liver fat content in
      patients with hypertriglyceridemia and non-alcoholic fatty liver disease: A
      double-blind, randomized, placebo-controlled study.
AB  - BACKGROUND: Treatment with omega-3 fatty acids and fenofibrates reduces serum
      triglyceride levels, but few studies have compared the effect of these agents on
      liver fat. OBJECTIVE: The aim of the EFFECT I trial (NCT02354976) was to
      determine the effects of free omega-3 carboxylic acids (OM-3CA) and fenofibrate
      on liver fat in overweight or obese individuals with non-alcoholic fatty liver
      disease and hypertriglyceridemia. METHODS: Seventy-eight patients were randomized
      to receive oral doses of 4 g OM-3CA (n = 25), 200 mg fenofibrate (n = 27), or
      placebo (n = 26) for 12 weeks in a double-blind, parallel-group study. Liver
      proton density fat fraction (PDFF) and volume, pancreas volume, and adipose
      tissue volumes were assessed by magnetic resonance imaging. RESULTS: Changes in
      liver PDFF at 12 weeks were not significantly different across treatment groups
      (relative changes from baseline: placebo, +4%; OM-3CA, -2%; and fenofibrate,
      +17%). The common PNPLA3 genetic polymorphism (I148M) did not significantly
      influence the effects of OM-3CA or fenofibrate on liver PDFF. Fenofibrate
      treatment significantly increased liver and pancreas volumes vs placebo
      treatment, and the changes in liver and pancreas volumes were positively
      correlated (rho 0.45, P = .02). Total liver fat volume increased significantly in
      patients using fenofibrate vs OM-3CA (+23% vs -3%, P = .04). Compared with OM
      3CA, fenofibrate increased total liver fat and liver volume. Serum triglycerides
      decreased with OM-3CA (-26%, P = .02) and fenofibrate (-38%, P < .001) vs
      placebo. In contrast to OM-3CA, fenofibrate reduced plasma docosahexaenoic acid
      levels and increased plasma acetylcarnitine and butyrylcarnitine levels,
      estimated delta-9 desaturase activity and the concentration of urine F2
      isoprostanes. CONCLUSIONS: OM-3CA and fenofibrate reduced serum triglycerides but
      did not reduce liver fat. Fenofibrate increased total liver volume and total
      liver fat volume vs OM-3CA, indicating a complex effect of fenofibrate on human
      hepatic lipid metabolism.

PMID- 30197274
TI  - BLIMP1 transcriptionally induced by EGFR activation and post-translationally
      regulated by proteasome and lysosome is involved in keratinocyte differentiation,
      migration and inflammation.
AB  - BACKGROUND: B lymphocyte-induced maturation protein-1 (BLIMP1) is a
      transcriptional repressor, and plays a crucial role in the regulation of
      development and functions of various immune cells. Currently, there is limited
      understanding about the regulation of BLIMP1 expression in keratinocytes and
      crosstalk between EGFR and BLIMP1 in skin homeostasis. OBJECTIVE: The aim of the
      study was to investigate the regulation and functional link between EGFR and
      BLIMP1 in human epidermal keratinocytes. METHODS: Immunoblotting and Q-PCR were
      used to determine the molecular mechanism of BLIMP1 expression induced by EGFR in
      primary human epidermal keratinocytes (NHEK) and HaCaT cells. In functional
      assay, effects of BLIMP1 knockdown on EGFR-mediated cytokine production,
      differentiation, and migration in NHEK were evaluated by Q-PCR, ELISA,
      immunoblotting, and/or wound-healing assay. RESULTS: EGFR activation by EGFR
      ligands could upregulate the protein and mRNA levels of BLIMP1 in NHEK and HaCaT
      cells. This effect was dependent on PKC, p38, and ERK activation. Additionally,
      the stability of BLIMP1 protein was under the control of the proteasome and
      lysosome degradation systems. EGF could also upregulate BLIMP1 expression in skin
      squamous cell carcinomas. In addition, BLIMP1 knockdown enhanced the EGFR
      mediated IL8, CXCL5 and IL6 gene expression and keratinocyte migration, but
      reduced the EGFR-mediated suppression of differentiation marker K10. CONCLUSIONS:
      Our findings shed new insights into the regulation of BLIMP1 expression by EGFR
      mediated gene transcription and proteasome/lysosome-mediated degradation in
      keratinocytes. Functionally, BLIMP1 is a negative regulator of EGF-induced
      inflammation and migration in keratinocytes, and exerts a gene-specific
      regulation on keratinocyte differentiation.

PMID- 30197275
TI  - The utility of EEG monitoring in neonates with hyperammonemia due to inborn
      errors of metabolism.
AB  - BACKGROUND: Continuous EEG studies demonstrate that neonates with seizures due to
      cerebral pathology, such as hypoxia ischemia, exhibit predominantly
      electrographic seizures (i.e. those only detected with EEG because they lack
      clinical features). Previous small case series demonstrate EEG changes and
      seizures during hyperammonemia associated with inborn errors of metabolism (IEM)
      but there are no reports utilizing continuous EEG in these conditions. OBJECTIVE:
      To characterize seizures and evaluate the utility of continuous EEG recording
      during hyperammonemia due to inborn errors of metabolism. METHODS: We
      retrospectively reviewed medical records and EEG tracings of neonates who
      presented with hyperammonemia due to inborn errors of metabolism who had
      continuous EEG and full medical records available for review, including follow
      up. RESULTS: Eight neonates with hyperammonemia were studied, 7 had urea cycle
      defects: Argininosuccinate lyase deficiency [3], (ornithine transcarbamylase
      deficiency [3], carbomyl phosphate synthase deficiency [1] and one had an organic
      acidemia: Methylmalonic acidemia [1]. Most common presentations were lethargy and
      poor feeding at 12-72 h of life. The highest blood ammonia level was 874 MUmol/L
      (median); range 823-1647 MUmol/L (normal value <50 MUmol/L in term neonates).
      Seven were treated with hemodialysis in addition to nitrogen scavengers. Seven
      neonates had seizures; six had only electrographic seizures. Seizures initially
      occurred within 24-36 h of clinical presentation, sometimes with normal ammonia
      and glutamine levels. Neonates with seizures all lacked state changes on EEG.
      Inter burst interval duration correlated with degree of hyperammonemia. Two cases
      with normal plasma ammonia but increasing interburst interval duration were
      proven to have stroke by MRI. CONCLUSIONS: Seizures occur frequently in neonates
      with hyperammonemia; most can be detected only with continuous EEG. Seizures may
      occur when ammonia and glutamine levels are normal. Interburst interval duration
      is associated with ammonia levels or cerebral dysfunction from other brain
      pathology. Continuous EEG can be a useful tool for managing infants with
      hyperammonemia and may be essential for seizure management especially for infants
      in deep metabolic coma.

PMID- 30197276
TI  - Worldwide Analysis of Radiology Access and Education for Stroke Care: View From
      Abroad From 14 Countries.

PMID- 30197277
TI  - Sphingolipids and their enigmatic role in asthma.
AB  - Asthma is defined as a chronic inflammatory condition in the lung and is
      characterized by episodic shortness of breath with expiratory wheezing and cough.
      Asthma is a serious public health concern globally with an estimated incidence
      over 300 million. Asthma is a complex disease in that it manifests as disease of
      gene and environmental interactions. Sphingolipids are a unique class of lipids
      involved in a host of biological functions ranging from serving as key cellular
      membrane lipids to acting as critical signaling molecules. To date sphingolipids
      have been studied across various human conditions ranging from neurological
      disorders to cancer to infection to autoimmunity. This review will focus on the
      role of sphingolipids in asthma development and pathology with particular focus
      on the role of mast cell sphingolipid biology.

PMID- 30197278
TI  - Loss of muscle mass during preoperative chemotherapy as a prognosticator for poor
      survival in patients with colorectal liver metastases.
AB  - BACKGROUND: The survival impact of specific body composition changes during
      preoperative chemotherapy in patients with colorectal liver metastases undergoing
      curative-intent surgery remains unclear. This study aimed to determine the impact
      of changes in body weight and muscle mass during preoperative chemotherapy on
      survival after hepatectomy in patients with colorectal liver metastases. METHODS:
      Consecutive patients with colorectal liver metastases undergoing preoperative
      chemotherapy and curative hepatectomy during 2009-2013 were retrospectively
      analyzed. Recurrence-free and overall survival were examined according to body
      compositions, including muscle mass, as measured by skeletal muscle index (area
      of muscle [cm2]/square of height [m2]), and body weight before and after
      preoperative chemotherapy. RESULTS: The median follow-up duration in overall 169
      patients was 47 months. Skeletal muscle index and body weight changed
      significantly during chemotherapy (skeletal muscle index: -0.52 cm2/m2, P = .03;
      body weight: +1.1 kg, P = .002). Patients with major muscle mass loss (>=7%) had
      significantly shorter median RFS than patients with no or minor muscle mass loss
      (<7%) (9.6 months vs 15.9 months; P = .02). Although major muscle mass loss was
      associated with poor outcome, skeletal muscle index before or after preoperative
      chemotherapy was not associated with recurrence-free or overall survival. On
      multivariate analysis, major muscle mass loss was independently associated with
      poorer recurrence-free survival (hazard ratio, 1.76; P = .045). CONCLUSION: Major
      loss of muscle mass but not body weight loss during preoperative chemotherapy is
      significantly associated with poor recurrence-free survival after hepatectomy in
      patients with colorectal liver metastases. The mechanisms mediating this
      association may inform future trials on maintaining muscle mass with dedicated
      nutrition and exercise programs to improve outcomes.

PMID- 30197279
TI  - Common mistakes when using large databases for surgical research.

PMID- 30197280
TI  - The location of the primary colon cancer has no impact on outcomes in patients
      undergoing cytoreductive surgery for peritoneal metastasis.
AB  - BACKGROUND: The impact of the location of colorectal cancer on patient outcomes
      has been reported in several settings. The objective of this study was to assess
      the prognostic impact of the location of the primary colon cancer among patients
      with colorectal cancer peritoneal metastases undergoing complete cytoreductive
      surgery. METHODS: Using the prospectively maintained clinical and biological
      digestive peritoneal metastasis database of the BIG-RENAPE network, we identified
      796 patients treated by a complete cytoreductive surgery between January 2004 and
      January 2017 for colorectal cancer peritoneal metastases in 16 different
      institutions. The 2 primary endpoints were overall survival and progression-free
      survival. To evaluate the impact on overall survival and progression-free
      survival of potential prognostic factors (including the location of the primary
      colorectal cancer), these factors were included in univariate and multivariate
      Cox proportional hazard models. RESULTS: Right-sided colorectal cancers were more
      often BRAF mutated and had microsatellite instability, whereas the frequency of
      RAS mutation was similar between right-sided and left-sided colorectal cancers.
      After a median follow-up time of 3.3 years, there was no significant difference
      in overall survival or progression-free survival according to tumor side. The
      lack of effect of tumor location on overall survival and progression-free
      survival was consistent across subgroups. CONCLUSION: Among patients undergoing
      complete cytoreductive surgery for peritoneal metastases, the site of the primary
      colorectal cancer was not associated with differences in progression-free
      survival or overall survival. Tumor side should not be used as a stratification
      factor in trials of colorectal cancer peritoneal metastases and should not be
      used in the selection process of patients for cytoreductive surgery.

PMID- 30197281
TI  - Recurrence risk of a hypotonic hyporesponsive episode in two Australian
      specialist immunisation clinics.
AB  - BACKGROUND: A hypotonic hyporesponsive episode (HHE) is a well-described adverse
      event following immunisation (AEFI) in young children. There is limited data
      regarding recurrence post re-vaccination. METHOD: A retrospective analysis of
      HHEs reported to two tertiary paediatric hospitals in Australia: The Royal
      Children's Hospital, Melbourne [2006-11] and the Children's Hospital Westmead,
      Sydney [1997-2014]. HHE definition level of confidence was allocated according to
      Brighton Collaboration (BC) criteria and defined immediate if within 30 min post
      vaccination. The Australian Immunisation Register (AIR) was utilised to document
      current immunisation status. RESULTS: 235 HHE cases (135 Melbourne, 100 Sydney)
      were identified: 47% were female and 67% (157/235) occurred following the routine
      dose one vaccines at 6-8 weeks of age. Median time following immunisation was 120
      min (range 1 min to 14 days) An immediate HHE occurred in 43% (102/235) and by BC
      criteria, 74% (173/235) were level 1 (definite). Subsequent vaccines were
      administered under supervision in hospital in 37% overall (86/235); 43% (58/135)
      in Melbourne and 28% (28/100) in Sydney. HHE recurrence rate was 3% (7/235) [95%
      confidence interval 1-6%]. AIR records were available in 94% (221/235). At a
      median age of 3.1 years, 84% (186/221) were up-to-date with recommended vaccines.
      CONCLUSION: This study highlights the importance of specialist immunization
      clinics in supporting the National Immunisation Program, through follow-up and
      management of serious adverse events following immunization.

PMID- 30197282
TI  - Antibody persistence and safety and immunogenicity of a second booster dose nine
      years after a first booster vaccination with a reduced antigen diphtheria-tetanus
      acellular pertussis vaccine (Tdap) in adults.
AB  - BACKGROUND: Over the last decades, pertussis showed periodic increases in its
      incidence among adults, despite being a vaccine-preventable disease. METHODS:
      This phase III, multicenter, extension study (NCT00489970) was conducted in
      adults from the United States, followed at Year (Y) 5 and Y9 post-vaccination
      with a dose of reduced-antigen-content tetanus-diphtheria-acellular pertussis
      vaccine containing either 3 (Tdap-B group) or 5 pertussis components (Tdap-A
      group). Willing participants in Tdap groups and newly-recruited participants
      (Control group) received one Tdap-B dose at Y9. Antibody persistence (at Y5 and
      Y9) and safety of Tdap-B at Y9 were assessed. Non-inferiority of immune response
      elicited by 2 Tdap doses was evaluated at Y9: (i) versus one Tdap-B dose for
      diphtheria and tetanus in terms of seroprotection rates; (ii) for all antigens in
      terms of booster response rates (Tdap-B and Tdap-A groups versus Control group);
      and (iii) for pertussis antigens in terms of geometric mean concentrations (GMCs)
      versus a 3-dose series of a combined diphtheria-tetanus-acellular pertussis
      vaccine (DTPa) administered during infancy. RESULTS: 1257 participants were
      enrolled at Y5 and 809 participants were vaccinated at Y9. Seroprotection rates
      in both Tdap groups were >=98.4% and >=98.0% (Y5) and >=98.3% and >=98.1% (Y9)
      for diphtheria and tetanus, respectively. For pertussis antigens, antibody
      concentrations above assay cut-offs were observed for >=76.6% (Y5) and >=84.9%
      (Y9) of participants in Tdap groups. At Y9, one month post-Tdap vaccination,
      comparable seroprotection/seropositivity rates and antibody GMCs were observed
      among groups. Non-inferiority of immune responses in both Tdap groups was
      demonstrated when compared to the Control group for diphtheria and tetanus and to
      a 3-dose DTPa series for pertussis antigens. Non-inferiority criteria in terms of
      booster response were not met for all antigens. No safety concerns were raised.
      CONCLUSION: A second dose of Tdap-B administered in adults, 9 years after initial
      Tdap vaccination, is immunogenic and well-tolerated.

PMID- 30197283
TI  - Biological and molecular characterization of ArkGA: A novel Arkansas serotype
      vaccine that is highly attenuated, efficacious, and protective against homologous
      challenge.
AB  - Almost all commercial poultry are vaccinated against avian coronavirus infectious
      bronchitis virus (IBV) using live attenuated vaccines mass administered by spray
      at day of hatch. Although many different types of IBV vaccines are used
      successfully, the ArkDPI serotype vaccine, when applied by spray, does not infect
      and replicate sufficiently to provide protection against homologous challenge. In
      this study, we examined a different Ark vaccine strain (Ark99), which is no
      longer used commercially due to its reactivity in one day old chicks, to
      determine if it could be further attenuated by passage in embryonated eggs but
      still provide adequate protection. Further attenuation of the Ark99 vaccine was
      achieved by passage in embryonated eggs but ArkGA P1, P20, and P40 (designated
      ArkGA after P1) were still too reactive to be suitable vaccine candidates.
      However, ArkGA P60 when given by spray had little or no vaccine reaction in one
      day old broiler chicks, and it induced protection from clinical signs and
      ciliostasis following homologous challenge. In addition, vaccinated and
      challenged birds had significantly less challenge virus, an important measure of
      protection, compared to non-vaccinated and challenged controls. The full-length
      genomes of viruses from egg passages 1, 20, 40, and 60 were sequenced using the
      Illumina platform and the data showed single nucleotide polymorphisms (SNPs) had
      accumulated in regions of the genome associated with viral replication,
      pathogenicity, and cell tropism. ArkGA P60 accumulated the most SNPs in key genes
      associated with pathogenicity (polyprotein gene 1ab) and cell tropism (spike
      gene), compared to previous passages, which likely resulted in its more
      attenuated phenotype. These results indicate that the ArkGA P60 vaccine is safe
      for spray vaccination of broiler chicks and induces suitable protection against
      challenge with pathogenic Ark-type virus.

PMID- 30197284
TI  - Plant lyophilisate carrying S-HBsAg as an oral booster vaccine against HBV.
AB  - A formulation of a defined antigen dosage together with an appropriate and
      convenient immunisation regime are the main problems of a plant-derived oral
      vaccine against HBV. Both factors have to be mutually adjusted to ensure
      efficacious vaccination and to minimise the risk of oral tolerance acquisition.
      As based on previous research, solely oral immunisation appears to be of limited
      effectiveness, but a combined immunisation scheme via injection priming and oral
      boosting can be proposed. Thus, the previously optimised plant lyophilisate with
      accumulated S-HBsAg was orally administered in a series of mouse immunisation
      trials. The impact of various S-HBsAg oral dosages and concentrations on the
      induction of an active immune response was studied. Immunisation via i.m. priming
      followed by double oral boosting in 6-week intervals was comparably efficient as
      standard i.m. vaccination. Among the tested dosages, 2* 5 or 200 ng triggered
      effective and exclusively systemic responses. Mucosal adjuvants CTB or quillaja
      bark saponins as well as alhydrogel either had no or a negative effect on immune
      response, which indicates that a low-dosed plant lyophilisate as an oral booster
      vaccine may not require exogenous adjuvants. Additionally, a positive effect of S
      HBsAg encapsulation in lyophilised cells on immune response stimulation was
      confirmed by comparison with the antigen released in the plant extract. The low
      dosed plant lyophilisate with concentrated S-HBsAg was proven as an effective and
      convenient oral booster vaccine. Results of immunisation via a mixed injection
      oral route provide the foundation for research on further standardisation of a
      plant-derived oral vaccine against HBV and details of immune response together
      with effects for health condition.

PMID- 30197286
TI  - In Vitro Evaluation of Aortic Stent Graft Deployment Accuracy in the Distal
      Landing Zone.
AB  - OBJECTIVES: Thoracic endovascular aortic repair technology focuses on accurately
      deploying the stent graft in the proximal landing zone in the proximal to distal
      direction. The aim of this in vitro study was to evaluate the accuracy of stent
      graft deployment in the distal landing zone. METHODS: It was hypothesised that a
      reverse implantation mechanism (in a distal to proximal deployment direction,
      when the operator starts to open the endoprosthesis from distal to proximal),
      might enhance landing accuracy in the distal LZ. The aim was to investigate this
      hypothesis by implanting stent grafts into the 3D printed aortas with the
      currently available deployment mechanism. Based on two human patients' computed
      tomography angiography scans, two aortas were 3D printed at 1:1 scale: "straight"
      and "crooked" aortas with distal aortic tortuosity of 1.006 and 1.078,
      respectively. They were used in order to test three endoprostheses (E-vita
      THORACIC 3G, Relay Plus, Valiant Captivia) 10 times by implanting them in three
      ways: proximal landing in the aneurysm, proximal landing in another stent graft,
      reverse implantation (via simulated antegrade access). The aim was to land just
      above the target vessel's upper edge. The distance to the target vessel and wedge
      apposition were assessed under a direct view using caliper. RESULTS: The distance
      to the target vessel was 3 mm (IQR 0; 8) if the stent graft landed proximally in
      aneurysm, 2 mm (IQR 0; 5) if it landed proximally in another stent graft, and 0
      mm (IQR 0; 0) when reverse implantation was applied. The distance to the target
      vessel measuring 5 mm or occurred in 45%, 30%, and 0%, respectively. Overall the
      median wedge apposition after stent graft implantation was 0 mm (IQR 0; 0) in the
      "straight" versus 18 mm (IQR 15; 20) in the "crooked" aorta (p < .001).
      CONCLUSIONS: Reverse stent graft deployment is associated with more accurate
      landing in the distal landing zone. Distal aortic tortuosity constitutes an
      important impediment to covering the distal LZ's entire circumference with a
      stent graft.

PMID- 30197285
TI  - Co-delivery of a CD4 T cell helper epitope via covalent liposome attachment with
      a surface-arrayed B cell target antigen fosters higher affinity antibody
      responses.
AB  - Liposomal vaccines incorporating adjuvant and CD4 T cell helper peptides enhance
      antibody responses against weakly immunogenic B cell epitopes such as found in
      the membrane proximal external region (MPER) of the HIV-1 gp41 subunit. While the
      inclusion of exogenous helper peptides in vaccine formulations facilitates
      stronger and more durable antibody responses, the helper peptide incorporation
      strategy per se may influence the overall magnitude and quality of B cell target
      antigen immunogenicity. Both variability in individual peptide encapsulation as
      well as the potential for liposome surface-associated helper peptides to
      misdirect the humoral response are potential parameters impacting outcome. In
      this study, we used MPER/liposome vaccines as a model system to examine how the
      mode of the potent LACK T helper peptide formulation modulates antibody responses
      against the MPER antigen. We directly compared liposome surface-arrayed palmitoyl
      LACK (pLACK) versus soluble LACK (sLACK) encapsulated in the liposomes and free
      in solution. Independent of LACK formulation methods, dendritic cell activation
      and LACK presentation were equivalent in vivo. The frequency of MPER-specific GC
      B cells promoted by sLACK was higher than that stimulated by pLACK formulation, a
      finding associated with a significantly greater frequency of LACK-specific GC B
      cells induced by pLACK. While there were no significant differences in the
      quantity of MPER-specific serological responses, the MPER-specific antibody titer
      trended higher with sLACK formulated vaccines at the lower dose of LACK. However,
      pLACK generated relatively greater MPER-specific antibody affinities than those
      induced by sLACK-formulated vaccines. Overall, the results suggest that liposomal
      surface-associated LACK enhances immunogenicity of LACK through better engagement
      of LACK-specific B cells. Of note, this is not detrimental to the induction of
      MPER-specific immune responses; rather, the elicitation of higher affinity anti
      MPER antibodies benefits from augmented help delivered via covalent linkage of
      the pLACK CD4 T cell epitope in conjunction with MPER/liposome presentation.

PMID- 30197288
TI  - Cerebral Autosomal Dominant Arteriopathy (CADASIL) with cardiac involvement
      (ANOCA) and subcortical leukencephalopathy.
AB  - We report a rare case of a CADASIL-syndrome with cardiac involvement presenting
      as ANOCA (angina in the absence of obstructive coronary artery disease). Our case
      highlights the added value of non-invasive fractional flow reserve (FFR)CT over
      coronary CT angiography (CTA), and recommends CTA as useful indication in CADASIL
      patients for screening of occult coronary artery disease (CAD).

PMID- 30197287
TI  - Prognostic Impact of Asymptomatic Carotid Artery Stenosis in Patients Undergoing
      Coronary Artery Bypass Grafting.
AB  - OBJECTIVES: The aim of this study was to evaluate the prognostic impact of
      untreated asymptomatic carotid artery stenosis (CS) in patients undergoing
      isolated coronary artery bypass grafting (CABG). METHODS: This was a post hoc
      analysis of data from a prospective multicentre observational study. Patients
      without history of stroke or transient ischaemic attack from the multicentre E
      CABG registry who were screened for CS before isolated CABG were included.
      RESULTS: Among 2813 patients screened by duplex ultrasound and who did not
      undergo carotid intervention for asymptomatic CS, 11.1% had a stenosis of 50-59%,
      6.0% of 60-69%, 3.1% of 70-79%, 1.4% of 80-89%, 0.5% of 90-99%, and 1.1% had
      carotid occlusion. In the screened population post-operative stroke occurred in
      25 patients (0.9%), with an incidence of 1.5% among patients with CS >= 50% (n =
      649). Pre-operative screening had not found a relevant CS in 15 of 25 patients
      suffering stroke after CABG. Brain imaging identified cerebral ischaemic injury
      in 20 patients, which was bilateral in five patients (25%), ipsilateral to a CS
      >= 50% in six (30%), and ipsilateral to a CS >= 70% in three (15%). In
      univariable analysis, the severity of CS was associated with a significantly
      increased risk of stroke (CS < 50%, 0.7%; 50-59%, 1.0%; 60-69%, 0.6%; 70-79%,
      1.2%; 80-89%, 5.1%; 90-99%, 7.7%; occluded, 6.7%, p < .001). In multivariable
      analysis, a CS of 90-99% (OR 12.03, 95% CI 1.34-108.23) and the presence of an
      occluded internal carotid artery (OR 8.783, 95% CI 1.820-42.40) were independent
      predictors of stroke along with urgency of the procedure, severe massive bleeding
      according to the E-CABG classification, and the presence of a porcelain ascending
      aorta. CONCLUSIONS: Among screened patients with untreated asymptomatic patients,
      CS >= 90% was an independent predictor of post-operative stroke. As this
      condition has a low prevalence and when left untreated is associated with a
      relatively low rate of stroke, pre-operative screening of asymptomatic CS before
      CABG may not be justified. CLINICAL TRIAL REGISTRATION:
      https://clinicaltrials.gov. Unique identifier: NCT02319083.

PMID- 30197289
TI  - Mechanical and morphological response of confluent epithelial cell layers to
      reinforcement and dissolution of the F-actin cytoskeleton.
AB  - The F-actin cytoskeleton and its connection to the plasma membrane provide
      structure and shape of epithelial cells. In this study we focus on the impact of
      the F-actin cytoskeleton on the morphology and mechanical behaviour of confluent
      epithelial cells. F-actin depolymerisation was fostered by Latrunculin A, while
      depolymerisation was allayed by Jasplakinolide. The impact of drug treatment on
      cellular mechanics was measured using atomic force microscopy based active
      microrheology and force-indentation curves, while morphology was monitored by AFM
      imaging, electric cell-substrate impedance sensing (ECIS) experiments and
      fluorescence microscopy. A softening and fluidisation of the cells upon
      dissolution of F-actin was observed, accompanied by reduction of cell-substrate
      and cell-cell contacts and an altered topography. The strengthening of actin
      filaments upon Jasplakinolide treatment was mirrored in several mechanical
      properties. The largest impact was on the cellular viscosity. The cells were,
      however, capable of restoring their initial phenotypes, e.g., amount of actin,
      intercellular and cell-substrate interactions.

PMID- 30197290
TI  - [Autologous breast reconstruction by deep inferior epigastric free flap: Classic
      and minimally invasive extraperitoneal approaches].
AB  - Perforator free flaps allow breast reconstructions " like with like " with skin
      and fat, excluding mammary gland, with a low morbidity. Those autologous
      reconstructions prevent material associated infections, capsular contracture and
      implant replacements, associated to breast reconstructions including implants.
      DIEP flap was described in 1994 to reduce the morbidity faced with TRAM flaps
      harvest. It only includes sub-umbilical skin and deep epigastric vessels. Deep
      inferior epigastric vessels harvest requires rectus abdominis muscle sheet
      opening and traction on rectus muscles, both associated with increased risks of
      abdominal bulges. Since 2014, we developed a minimally invasive DIEP harvest by
      totally extra-peritoneal laparoscopic dissection of epigastric vessels with a 70%
      reduction of aponeurosis opening and avoiding traction on rectus' motor nerves.
      We report both classic and minimally invasive DIEP harvest techniques. Bresat
      reconstructions by DIEP require that the ombilicus can be transposed and are
      indicated for all patients with need for skin inset, particularly secondary
      breast reconstructions. The reconstructed breast as a volume that follows
      patients weight variations and allows for improved quality of life on a long
      term. Its minimally invasive totally extra peritoneal harvest by laparoscopy,
      with or without robotic assistance, offers a reduced morbidity and might allows
      for reduced risks of abdominal wall weakness on a long-term.

PMID- 30197291
TI  - [Breast reconstruction by prosthesis].
AB  - Breast reconstruction by prosthesis remains the most used in the world and even
      tends to increase again at the expense of musculo-cutaneous flaps since the
      systematic use, in recent years, of adipocytes grafts (lipofilling) before and/or
      after in place of the implant. This simpler technique is often preferred by
      patients who want to avoid scars and pain away from the chest area. The use of
      different implant forms, fat injection, abdominal advancement flaps, biological
      or synthetic matrices can significantly improve the results of these
      reconstructions in secondary or immediate. All these techniques are detailed in
      the following article to show the different devices that allow to achieve this
      intervention with maximum security.

PMID- 30197292
TI  - [Breast reconstruction with Muscle-Sparing Latissimus Dorsi flap combined to a
      Thoraco-Abdominal advancement flap and fat grafting].
AB  - The Latissimus Dorsi flap (or LD flap) was first described by the Tansini in 1896
      and published in 1906. It concerned a case of chest wall reconstruction after
      breast amputation. The use of the LD flap in all its variants is very frequent in
      breast reconstruction. In these indications, the muscle is harvested for skin
      paddle vascularization and/or for bringing volume to the reconstructed breast.
      When all or most of the muscle is taken, its motor function is completely lost.
      The functional sequelae due to the loss of the latissimus dorsi muscle are then
      definitive. Tobin et al. showed that the LD muscle can be separated into two
      flaps based on the division of the thoracodorsal artery; the concept of muscle
      sparing was then posed (Muscle-Sparing Latissimus Dorsi [MSLD]). The MSLD as we
      perform now, concerns only a thin muscle strip and preserves 95% of the LD muscle
      with its vascularization and motor innervation. This technique is quick with very
      low donor site morbidity. The functional sequelae and postoperative complications
      appear limited compared to the harvest of a total LD whatever the posterior scar.
      The volume of the breast to be reconstructed is obtained by several sessions of
      fat grafting. We present here the anatomical bases and the surgical technique of
      the muscle-sparing latissimus dorsi associated with a thoracoabdominal
      advancement flap and fat grafting in breast reconstruction.

PMID- 30197293
TI  - [Response to the article "The portfolio of the plastic surgery intern. A tool for
      training". A context to be specified, a point of view to qualify].

PMID- 30197294
TI  - Pentoxifylline protects against loss of function and renal interstitial fibrosis
      in chronic experimental partial ureteral obstruction.
AB  - Tubulointerstitial fibrosis (TIF) is a hallmark of chronic kidney disease
      resulting from diverse etiologies and predicts severity and progression of the
      kidney disease. To investigate the pathogenesis of TIF, complete unilateral
      ureteral obstruction (UUO) is the most widely used animal model. However, UUO
      precludes evaluation of renal function. In the present study, we created a rat
      model of chronic partial ureteral obstruction (PUO), which allowed assessment of
      renal function at different intervals after obstruction. We examined the effects
      of pentoxifylline (PTF), a phosphodiesterase inhibitor used clinically to treat
      peripheral artery disease, on renal function and TIF. Studies were performed in
      sham-PUO rats and rats with 14-day PUO or 30-day PUO receiving vehicle in
      drinking water or PTF (400 mg/liter in drinking water). At day-14 PUO, glomerular
      filtration rate (GFR) was markedly and similarly depressed in rats receiving
      vehicle or PTF as compared with sham-operated rats. However, at day-30 PUO, GFR
      in rats receiving PTF was significantly higher than that in rats receiving
      vehicle, approaching the level seen in the sham-operated rats. At day-30 PUO,
      histologic studies also revealed a marked reduction of TIF in rats treated with
      PTF as compared with the rats receiving vehicle in drinking water. Western blot
      analysis demonstrated that at day-30 the expression of alpha-smooth muscle actin
      (an indicator of renal fibrosis) in the medulla was significantly reduced in PUO
      rats treated with PTF. In conclusion, PTF treatment ameliorated renal fibrosis
      and helped preserve renal function in a rodent model of PUO.

PMID- 30197296
TI  - Identification of ICAT as an APC Inhibitor, Revealing Wnt-Dependent Inhibition of
      APC-Axin Interaction.
AB  - Adenomatous polyposis coli (APC) and Axin are core components of the beta-catenin
      destruction complex. How APC's function is regulated and whether Wnt signaling
      influences the direct APC-Axin interaction to inhibit the beta-catenin
      destruction complex is not clear. Through a CRISPR screen of beta-catenin
      stability, we have identified ICAT, a polypeptide previously known to block beta
      catenin-TCF interaction, as a natural inhibitor of APC. ICAT blocks beta-catenin
      APC interaction and prevents beta-catenin-mediated APC-Axin interaction,
      enhancing stabilization of beta-catenin in cells harboring truncated APC or
      stimulated with Wnt, but not in cells deprived of a Wnt signal. Using ICAT as a
      tool to disengage beta-catenin-mediated APC-Axin interaction, we demonstrate that
      Wnt quickly inhibits the direct interaction between APC and Axin. Our study
      highlights an important scaffolding function of beta-catenin in the assembly of
      the destruction complex and suggests Wnt-inhibited APC-Axin interaction as a
      mechanism of Wnt-dependent inhibition of the destruction complex.

PMID- 30197295
TI  - Differential m6A, m6Am, and m1A Demethylation Mediated by FTO in the Cell Nucleus
      and Cytoplasm.
AB  - FTO, the first RNA demethylase discovered, mediates the demethylation of internal
      N6-methyladenosine (m6A) and N6, 2-O-dimethyladenosine (m6Am) at the +1 position
      from the 5' cap in mRNA. Here we demonstrate that the cellular distribution of
      FTO is distinct among different cell lines, affecting the access of FTO to
      different RNA substrates. We find that FTO binds multiple RNA species, including
      mRNA, snRNA, and tRNA, and can demethylate internal m6A and cap m6Am in mRNA,
      internal m6A in U6 RNA, internal and cap m6Am in snRNAs, and N1-methyladenosine
      (m1A) in tRNA. FTO-mediated demethylation has a greater effect on the transcript
      levels of mRNAs possessing internal m6A than the ones with cap m6Am in the tested
      cells. We also show that FTO can directly repress translation by catalyzing m1A
      tRNA demethylation. Collectively, FTO-mediated RNA demethylation occurs to m6A
      and m6Am in mRNA and snRNA as well as m1A in tRNA.

PMID- 30197297
TI  - Structural Basis for Regulation of METTL16, an S-Adenosylmethionine Homeostasis
      Factor.
AB  - S-adenosylmethionine (SAM) is an essential metabolite that acts as a cofactor for
      most methylation events in the cell. The N6-methyladenosine (m6A)
      methyltransferase METTL16 controls SAM homeostasis by regulating the abundance of
      SAM synthetase MAT2A mRNA in response to changing intracellular SAM levels. Here
      we present crystal structures of METTL16 in complex with MAT2A RNA hairpins to
      uncover critical molecular mechanisms underlying the regulated activity of
      METTL16. The METTL16-RNA complex structures reveal atomic details of RNA
      substrates that drive productive methylation by METTL16. In addition, we identify
      a polypeptide loop in METTL16 near the SAM binding site with an autoregulatory
      role. We show that mutations that enhance or repress METTL16 activity in vitro
      correlate with changes in MAT2A mRNA levels in cells. Thus, we demonstrate the
      structural basis for the specific activity of METTL16 and further suggest the
      molecular mechanisms by which METTL16 efficiency is tuned to regulate SAM
      homeostasis.

PMID- 30197298
TI  - alpha-Proteobacterial RNA Degradosomes Assemble Liquid-Liquid Phase-Separated RNP
      Bodies.
AB  - Ribonucleoprotein (RNP) granules play an important role in organizing eukaryotic
      mRNA metabolism via liquid-liquid phase separation (LLPS) of mRNA decay factors
      into membrane-less organelles in the cytoplasm. Here we show that the bacterium
      Caulobacter crescentus Ribonuclease (RNase) E assembles RNP LLPS condensates that
      we term bacterial RNP-bodies (BR-bodies), similar to eukaryotic P-bodies and
      stress granules. RNase E requires RNA to assemble a BR-body, and disassembly
      requires RNA cleavage, suggesting BR-bodies provide localized sites of RNA
      degradation. The unstructured C-terminal domain of RNase E is both necessary and
      sufficient to assemble the core of the BR-body, is functionally conserved in
      related alpha-proteobacteria, and influences mRNA degradation. BR-bodies are
      rapidly induced under cellular stresses and provide enhanced cell growth under
      stress. To our knowledge, Caulobacter RNase E is the first bacterial protein
      identified that forms LLPS condensates, providing an effective strategy for
      subcellular organization in cells lacking membrane-bound compartments.

PMID- 30197299
TI  - Methylation of Structured RNA by the m6A Writer METTL16 Is Essential for Mouse
      Embryonic Development.
AB  - Internal modification of RNAs with N6-methyladenosine (m6A) is a highly conserved
      means of gene expression control. While the METTL3/METTL14 heterodimer adds this
      mark on thousands of transcripts in a single-stranded context, the substrate
      requirements and physiological roles of the second m6A writer METTL16 remain
      unknown. Here we describe the crystal structure of human METTL16 to reveal a
      methyltransferase domain furnished with an extra N-terminal module, which
      together form a deep-cut groove that is essential for RNA binding. When presented
      with a random pool of RNAs, METTL16 selects for methylation-structured RNAs where
      the critical adenosine is present in a bulge. Mouse 16-cell embryos lacking
      Mettl16 display reduced mRNA levels of its methylation target, the SAM synthetase
      Mat2a. The consequence is massive transcriptome dysregulation in ~64-cell
      blastocysts that are unfit for further development. This highlights the role of
      an m6A RNA methyltransferase in facilitating early development via regulation of
      SAM availability.

PMID- 30197301
TI  - Daily Fasting Improves Health and Survival in Male Mice Independent of Diet
      Composition and Calories.
AB  - The importance of dietary composition and feeding patterns in aging remains
      largely unexplored, but was implicated recently in two prominent nonhuman primate
      studies. Here, we directly compare in mice the two diets used in the primate
      studies focusing on three paradigms: ad libitum (AL), 30% calorie restriction
      (CR), and single-meal feeding (MF), which accounts for differences in energy
      density and caloric intake consumed by the AL mice. MF and CR regimes enhanced
      longevity regardless of diet composition, which alone had no significant impact
      within feeding regimens. Like CR animals, MF mice ate quickly, imposing periods
      of extended daily fasting on themselves that produced significant improvements in
      morbidity and mortality compared with AL. These health and survival benefits
      conferred by periods of extended daily fasting, independent of dietary
      composition, have major implications for human health and clinical applicability.

PMID- 30197300
TI  - beta-Hydroxybutyrate Prevents Vascular Senescence through hnRNP A1-Mediated
      Upregulation of Oct4.
AB  - beta-hydroxybutyrate (beta-HB) elevation during fasting or caloric restriction is
      believed to induce anti-aging effects and alleviate aging-related
      neurodegeneration. However, whether beta-HB alters the senescence pathway in
      vascular cells remains unknown. Here we report that beta-HB promotes vascular
      cell quiescence, which significantly inhibits both stress-induced premature
      senescence and replicative senescence through p53-independent mechanisms.
      Further, we identify heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) as a
      direct binding target of beta-HB. beta-HB binding to hnRNP A1 markedly enhances
      hnRNP A1 binding with Octamer-binding transcriptional factor (Oct) 4 mRNA, which
      stabilizes Oct4 mRNA and Oct4 expression. Oct4 increases Lamin B1, a key factor
      against DNA damage-induced senescence. Finally, fasting and intraperitoneal
      injection of beta-HB upregulate Oct4 and Lamin B1 in both vascular smooth muscle
      and endothelial cells in mice in vivo. We conclude that beta-HB exerts anti-aging
      effects in vascular cells by upregulating an hnRNP A1-induced Oct4-mediated Lamin
      B1 pathway.

PMID- 30197302
TI  - Leucine Signals to mTORC1 via Its Metabolite Acetyl-Coenzyme A.
AB  - The mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) is a master
      regulator of cell growth and metabolism. Leucine (Leu) activates mTORC1 and many
      have tried to identify the mechanisms whereby cells sense Leu in this context.
      Here we describe that the Leu metabolite acetyl-coenzyme A (AcCoA) positively
      regulates mTORC1 activity by EP300-mediated acetylation of the mTORC1 regulator,
      Raptor, at K1097. Leu metabolism and consequent mTORC1 activity are regulated by
      intermediary enzymes. As AcCoA is a Leu metabolite, this process directly
      correlates with Leu abundance, and does not require Leu sensing via intermediary
      proteins, as has been described previously. Importantly, we describe that this
      pathway regulates mTORC1 in a cell-type-specific manner. Finally, we observed
      decreased acetylated Raptor, and inhibited mTORC1 and EP300 activity in fasted
      mice tissues. These results provide a direct mechanism for mTORC1 regulation by
      Leu metabolism.

PMID- 30197303
TI  - The Translational Machinery of Human CD4+ T Cells Is Poised for Activation and
      Controls the Switch from Quiescence to Metabolic Remodeling.
AB  - Naive T cells respond to T cell receptor (TCR) activation by leaving quiescence,
      remodeling metabolism, initiating expansion, and differentiating toward effector
      T cells. The molecular mechanisms coordinating the naive to effector transition
      are central to the functioning of the immune system, but remain elusive. Here, we
      discover that T cells fulfill this transitional process through translational
      control. Naive cells accumulate untranslated mRNAs encoding for glycolysis and
      fatty acid synthesis factors and possess a translational machinery poised for
      immediate protein synthesis. Upon TCR engagement, activation of the translational
      machinery leads to synthesis of GLUT1 protein to drive glucose entry.
      Subsequently, translation of ACC1 mRNA completes metabolic reprogramming toward
      an effector phenotype. Notably, inhibition of the eIF4F complex abrogates
      lymphocyte metabolic activation and differentiation, suggesting ACC1 to be a key
      regulatory node. Thus, our results demonstrate that translation is a direct
      mediator of T cell metabolism and indicate translation factors as targets for
      novel immunotherapeutic approaches.

PMID- 30197304
TI  - Practice strategies to improve primary care for chronic disease patients under a
      pay-for-value program.
AB  - BACKGROUND: Improving primary care for patients with chronic illness is critical
      to advancing healthcare quality and value. Yet, little is known about what
      strategies are successful in helping primary care practices deliver high-quality
      care for this population under value-based payment models. METHODS: Double-blind
      interviews in 14 primary care practices in the state of Michigan, stratified
      based on whether they did (n = 7) or did not (n = 7) demonstrate improvement in
      primary care outcomes for patients with at least one reported chronic disease
      between 2010 and 2013. All practices participate in a statewide pay-for
      performance program run by a large commercial payer. Using an implementation
      science framework to identify leverage points for effecting organizational
      change, we sought to identify, describe and compare strategies among improving
      and non-improving practices across three domains: (1) organizational learning
      opportunities, (2) approaches to motivating staff, and (3) acquisition and use of
      resources. RESULTS: We identified 10 strategies; 6 were "differentiating" - that
      is, more prevalent among improving practices. These differentiating strategies
      included: (1) participation in learning collaboratives, (2) accessing payer tools
      to monitor quality performance, (3) framing pay-for-performance as a practice
      transformation opportunity, (4) reinvesting earned incentive money in equitable,
      practice-centric improvement, (5) employing a care manager, and (6) using
      available technical support from local hospitals and provider organizations to
      support performance improvement. Implementation of these strategies varied based
      on organizational context and relative strengths. CONCLUSIONS: Practices that
      succeeded in improving care for chronic disease patients pursued a mix of
      strategies that helped meet immediate care delivery needs while also creating new
      adaptive structures and processes to better respond to changing pressures and
      demands. These findings help inform payers and primary care practices seeking
      evidence-based strategies to foster a stronger delivery system for patients with
      significant healthcare needs.

PMID- 30197305
TI  - Association measures for estimating semantic similarity and relatedness between
      biomedical concepts.
AB  - Association measures quantify the observed likelihood a term pair co-occurs
      versus their predicted co-occurrence together if by chance. This is based both on
      the terms' individual occurrence frequencies, and their mutual co-occurrence
      frequencies. One application of association scores is estimating semantic
      relatedness, which is critical for many natural language processing applications,
      such as clustering of biomedical and clinical documents and the development of
      biomedical terminologies and ontololgies. In this paper we propose a method of
      generating association scores between biomedical concepts to estimate semantic
      relatedness. We use co-occurrence statistics between Unified Medical Language
      System (UMLS) concepts to account for lexical variation at the synonymous level,
      and introduce a process of concept expansion that exploits hierarchical
      information from the UMLS to account for lexical variation at the hyponymous
      level. State of the art results are achieved on several standard evaluation
      datasets, and an in depth analysis of hyper-parameters is presented.

PMID- 30197306
TI  - An Initiative to Reduce Routine Viral Diagnostic Testing in Pediatric Patients
      Admitted with Bronchiolitis.
AB  - BACKGROUND: Bronchiolitis is a viral lower respiratory tract infection that
      causes significant morbidity and mortality in the pediatric population. Viral
      diagnostic testing (VDT) has been used to identify specific viral pathogens.
      However, current guidelines suggest that routine use of this testing is not
      advisable. For children admitted to a children's hospital from the pediatric
      emergency department (PED), the rate of VDT was 63%, which was higher than the
      national rate. A quality improvement project was conducted to reduce the use of
      routine VDT. METHODS: Key drivers of VDT were identified, and interventions,
      which included staff education about the cost and use of VDT and dissemination of
      a simplified cohorting policy aimed to eliminate VDT without medical necessity,
      were implemented through the PED and inpatient unit settings. RESULTS: Between
      January 2017 and April 2017, VDT use in all non-ICU patients admitted from the
      PED with bronchiolitis decreased from 63% to 12%. In the same time period,
      patients with VDT sent from the PED fell from 53% to 14%. A reduction in VDT for
      patients admitted with asthma exacerbation was also observed-from 24% to 0%
      demonstrating early spread of these effects. Cost savings of approximately $8,584
      per year in direct supply costs alone was documented. CONCLUSION: Using simple,
      low-cost interventions, including education and guideline refinement, the rate of
      VDT use for bronchiolitis was significantly reduced. Further directions for this
      project include the reduction of routine testing for patients with bronchiolitis
      who are admitted to the ICU or discharged for outpatient care.

PMID- 30197307
TI  - SLC30A8 Gene rs13266634 C/T Polymorphism in Type 1 Diabetes Children of Tamil
      Nadu, India.
AB  - OBJECTIVE: Zinc transporter 8 (ZnT8) is a multi-trans membrane protein situated
      in the insulin secretory granule of the islets of beta-cells and is identified as
      a novel auto-antigen in Type 1 diabetes (T1D). The gene coding for ZnT8 (solute
      carrier family 30 member 8; SLC30A8) is located in Chromosome 8q24.11. In this
      work it is aimed to identify the association of SLC30A8 rs13266634 C/T gene
      polymorphism with T1D in chosen children of Tamil Nadu, India. METHODS: The
      family based study is made on 121 T1D patients and 214 of their family members as
      control. The SLC30A8 gene rs13266634 C/T polymorphism is evaluated by polymerase
      chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: No
      significant differences was observed in allele (OR=0.92; CI=0.33 - 2.58; p=0.88)
      and genotype (CC: p=0.74; CT: p=0.82; TT: p=0.80) frequencies of rs13266634 C/T
      between T1D patients and controls. Transmission disequilibrium test (TDT) has
      identified over-transmission of mutant T allele from parents to affected children
      (T: U = 9:7) without statistical significance. Metaanalysis on the overall
      effects of rs13266634 C allele frequency was not different (p=0.10 and P
      heterogeneity = 0.99) in T1D patients upon comparison with control. CONCLUSION:
      The present study along with the meta-analysis does not show any substantial
      association of the rs13266634 C/T polymorphism with T1D development.

PMID- 30197308
TI  - [Inhibitory effect of andrographolide on angiogenesis induced by the supernatant
      from cultured tumor cells].
AB  - OBJECTIVE: To determine the effect of andrographolide (Andro) on angiogenesis of
      human umbilical vein endothelial cells (HUVECs).? Methods: HUVECs were treated
      with different concentrations of Andro and the cell viability was detected with
      Cell Counting Kit-8 (CCK-8). HUVECs were treated with half lethal dose (IC50) of
      Andro. Matrigel was used to make capillary formation of HUVECs and the effect of
      Andro on capillary formation was evaluated by calculating the percentage of
      capillary formation. Moreover, the effects of Andro and the supernatant from
      cultured A549 tumor cells on capillary formation were evaluated by calculating
      the percentage of capillary formation. The effect of Andro on the expression of
      matrix metalloproteinase-9 (MMP-9) was determined with Western blot.? Results:
      The cell viability of HUVECs decreased with the increase of Andro concentrations.
      IC50 was 20 MUmol/L. The capillary formation of HUVECs was inhibited when treated
      with 20 MUmol/L Andro for 24 hours. Moreover, Andro was able to antagonize the
      promotion of the capillary formation induced by the supernatant from cultured
      tumor cells. Andro could suppress the expression of MMP-9 and antagonize the
      capillary formation.? Conclusion: Andro inhibits the capillary formation of
      HUVECs and can antagonize the promotion of angiogenesis induced by the
      supernatant from cultured tumor cells.

PMID- 30197309
TI  - [Alterations in gene expression profiles in children with Type 2 diabetes
      mellitus and its mechanisms].
AB  - OBJECTIVE: To explore the mechanisms for Type 2 diabetes mellitus (T2DM) in
      children and provide genomic evidence for its early diagnosis and treatment.?
      Methods: The peripheral blood gene chip datasets from 12 children with T2DM and
      24 healthy children were retrieved from the Gene Expression Omnibus (GEO) at
      National Center for Biotechnology Information (NCBI). The differentially
      expressed genes were screened by R language software. GenCLiP 2.0, STRING, and
      Cytoscape software were used to analyze the biological functions, protein-protein
      interaction network, signal pathway, gene-pathway network, expression of key
      genes, and predictive value between the two differentially expressed genes.?
      Results: A total of 79 differentially expressed genes were identified. Among
      them, 58 (73.42%) were up-regulated, and 21 (26.58%) were down-regulated.
      Differentially expressed genes mainly involved molecular functions and biological
      processes, such as defensive response, response to external stimulus, and
      inflammatory responses. At the same time, they were mainly involved in the
      Leishmaniasis, cytokine-cytokine receptor interaction, Toll-like receptor
      signaling pathway. interleukin 1beta (IL-1beta), jun proto-oncogene (JUN), and IL
      8 were 3 important linking nodes in the protein-protein interaction network. JUN
      and IL-1beta were key genes, which were related to interleukin 17 (1L-17)
      signaling pathway, Toll-like receptor signaling pathway and so on. The expression
      of JUN gene in peripheral blood of children with T2DM was decreased while the
      expression of IL-1beta gene was increased. JUN and IL-1beta genes possessed
      certain diagnostic and predictive value in children with T2DM.? Conclusion: The
      gene expression profile of peripheral blood in children with T2DM changes
      significantly. The genes of JUN and IL-1beta are closely related to T2DM in
      children. IL-1beta gene expression level shows a better predictive value on T2DM
      in children.

PMID- 30197310
TI  - [Effect of methotrexate on regulation for the number of regulatory T cells and
      expression of Foxp3 in psoriasis].
AB  - OBJECTIVE: To explore the role of methotrexate (MTX) in regulating the number of
      regulatory T cells (Treg) and the mRNA expression of transcription factor Foxp3.?
      Methods: 1) We analyzed the number of Treg and the mRNA expression of Foxp3 by
      flow cytometry (FCM) and quantitative real-time PCR (qRT-PCR) respectively in
      patients with psoriasis vulgaris, patients with psoriasis vulgaris after the 8
      week treatment of MTX, and healthy people. 2) BALB/c female mice were smeared
      with imiquimod (IMQ) cream for 6 days. We recorded the change of the lesion in
      mice every day. The morphological changes of lesion in mice were evaluated by the
      psoriasis area and severity index (PASI) and HE staining. 3) The mouse model was
      randomly divided into a control group and an MTX group. The MTX group was treated
      with different doses of MTX (38.5 and 77.0 nmol/L) on the third day of this
      experiment. The morphological changes of lesion in mice were evaluated by PASI
      and HE staining. We tested the number of Treg and the expression level of Foxp3
      mRNA in splenic lymphocytes.? Results: 1) The number of Treg and the expression
      level of Foxp3 mRNA were lower in psoriasis vulgaris patients than those in the
      healthy control group (P<0.05). After 8-week treatment of MTX, the number of Treg
      was increased (P<0.05) and Foxp3 mRNA level was up-regulated (P<0.01). 2) Typical
      psoriasis-like skin lesions, such as red scaly skin plaque were found after
      topical application of IMQ. Both the number of Treg in the splenic lymphocytes of
      mice and the Foxp3 mRNA level of Treg were reduced by IMQ (P<0.01 and P<0.05). 3)
      Different doses of MTX for mice showed the ability to improve skin lesion,
      increase the number of Treg in the spleen of mice and Foxp3 mRNA level in
      psoriatic dermatitis of mice (P<0.05).? Conclusion: MTX is able to regulate the
      number of Treg and Foxp3 mRNA expression in psoriasis.

PMID- 30197312
TI  - [Types for 1 849 patients with urinary calculi and patients' clinical
      characteristics].
AB  - OBJECTIVE: To analyze types of urinary calculi and patients' clinical
      characteristics, and to explore the strategies for prevention and treatment of
      urinary calculi.? Methods: A total of 1 849 patients with urinary calculi were
      treated in the Department of Urology, the Third Xiangya Hospital of Central South
      University. The components were analyzed by infrared spectroscopy. The
      relationship between stone composition and clinical parameters was analyzed
      according to the clinical characteristics of the patients.? Results: The
      proportion of calcium oxalate stone or uric acid stone in male (84.1% or 7.7%)
      was higher than that in female (78.4% or 4.2%). The older patients were more
      likely to be diagnosed as uric acid stone. The proportions of uric acid stone in
      patients <18 years old, 18-<41 years old, 41-<66 years old, and >=66 years old
      were 0.0%, 1.6%, 6.6%, and 12.4%, respectively. There was no significant
      difference in the proportion of stones in patients with different BMI. There were
      no significant difference in the stone composition between the patients with or
      without urinary tract infection, hypertension or diabetes. The proportion of uric
      acid stones in patients with acidic urine was higher than the other types. The
      proportion of uric acid stones in patients with elevated creatinine (12.1%) was
      higher than that in the patients with normal creatinine (4.5%).? Conclusion:
      Elderly patients, or patients with high uric acid and renal insufficiency are
      more prone to uric acid stones. Regulation of urinary pH may be an important
      strategy for preventing and treating urinary calculi in Hunan Province.

PMID- 30197313
TI  - [Continuous lumbar plexus block reduces the incidence of early postoperative
      cognitive dysfunction in elderly patients undergoing hip arthroplasty].
AB  - OBJECTIVE: To observe the impacts of continuous lumbar plexus block (CLPB) on
      postoperative cognitive dysfunction (POCD) in elderly patients undergoing hip
      arthroplasty.? Methods: Sixty elderly patients scheduled for hip arthroplasty
      with general anesthesia, were randomly allocated into a CLPB group and a PCIA
      group (n=30 each). In the CLPB group, lumbar plexus block was performed before
      trachea intubation, and CLPB was used for postoperative analgesia. In the PCIA
      group, intravenous analgesia was controlled in patients after operation. Visual
      Analogue Scale (VAS) at 12, 24, and 48 h after operation was recorded. Mini
      Mental State Examination (MMSE) scale was used to evaluate the cognitive
      dysfunction at the 1st day before operation (D0) and at the 1st (D1), 3rd (D3),
      and 7th (D7) days after operation and the occurrence of POCD was recorded. S
      100beta concentrations were detected by ELISA at D1, D3, and D7. Postoperative
      adverse events were recorded.? Results: VAS scores at 12, 24, and 48 h after
      operation in the CLPB group were significantly lower than those in the PCIA group
      (P<0.05). Compared with the PCIA group, the MMSE scores were significantly higher
      (P<0.05), and the incidence of POCD at D1 and D3 was obviously reduced in the
      CLPB group (P<0.05). S-100beta concentration at D1 and D3 in the CLPB group was
      significantly lower than that in the PCIA group (P<0.05).? Conclusion:
      Application of CLPB in elderly patients undergoing hip arthroplasty could
      obviously relieve their postoperative pain, inhibit the production of S-100beta,
      and reduce the incidence of early postoperative cognitive dysfunction.

PMID- 30197311
TI  - [Anti-cicatricial and anti-restenosis effect of verapamil on anterior urethral
      stricture: A randomized controlled clinical trial].
AB  - OBJECTIVE: To evaluate the anti-cicatricial and anti-restenosis effect of
      verapamil on anterior urethral stricture.? Methods: A total of 32 patients
      received anterior urethral stricture were enrolled in this study. They were
      divided into 4 blocks according to the duration of previous urethral operations
      and dilations. Every block was further randomly divided into an experimental
      group and a control group. Experimental groups received 2 mL injection of
      verapamil around the anastomosis site of urethra before and after the surgery (2,
      4, 6, 8, and 10 weeks after the surgery), while the control groups only received
      the anastomosis surgery. After surgery, maximal urinary flow rate (Qmax) was
      examined for all patients once the catheter was removed. In addition, they were
      also conducted palpation of urethral scar range. The sum of long transverse
      diameters of urethral scar was measured, and the narrowest urethral inner
      diameter was examined. The Qmax was rechecked and the urethral scar range was
      assessed by penis color Doppler elastography after 12 weeks of surgery. The above
      4 indexes were used to evaluate the inhibitory effect of verapamil on urethral
      scar.? Results: The length of palpated urethral scar in the Block 1 to 4 of the
      experimental groups was (22.75+/-1.03), (21.25+/-0.25), (20.75+/-1.03), and
      (20.0+/-0.58) mm, respectively; and those in the control groups (26.00+/-0.82),
      (24.5+/-1.04), (25.75+/-1.65), and (28.25+/-1.75) mm, respectively. The Qmax
      rates in the Block 1 to 4 of the experimental groups were (11.85+/-0.77),
      (11.33+/-0.81), (10.23+/-0.26), and (10.35+/-0.17) mL/s, respectively; and those
      in the control groups were (10.85+/-0.39), (10.50+/-0.76), (10.53+/-1.00),
      (12.60+/-0.39) mL/s, respectively. The Qmax rates in the Block 1 to 4 of the
      experimental groups were (11.73+/-0.87), (10.65+/-0.25), (10.23+/-0.19), and
      (10.35+/-0.29) mL/s, respectively; and those in the control groups were (8.05+/
      0.28), (7.73+/-0.68), (7.53+/-0.92), and (9.60+/-0.32) mL/s, respectively. The
      narrowest diameters of urethral in the Block 1 to 4 of the experimental groups
      were (9.00+/-0.58), (7.50+/-2.89), (7.00+/-0.10), and (7.00+/-0.41) mm,
      respectively; and those in the control groups were (5.50+/-0.29), (5.00+/-0.41),
      (4.75+/-0.48), and (6.75+/-0.48) mm, respectively. The ultrasound strain ratio in
      the Block 1 to 4 of the experimental groups were 6.10+/-0.22, 6.10+/-0.17, 5.10+/
      0.16, and 6.90+/-0.19, respectively; and those in the control groups were 8.00+/
      0.25, 10.60+/-0.29, 11.30+/-0.16, and 8.90+/-0.33, respectively. Compared with
      the control groups, the experimental groups displayed smaller urethral scar
      range, less severe scarring, improved Qmax rates and wider inner diameters (all
      P<0.05).? Conclusion: Urethral regional injection of verapamil intraoperatively
      or postoperatively can prevent overgrowth of urethral scar tissues after the
      transperineal anastomosis surgery, and reduce the tendency of postoperative
      restenosis of anterior urethral stricture.

PMID- 30197314
TI  - [Dosimetric verification of flattening filter free model based on TrueBeam
      accelerator using ArcCheck system].
AB  - OBJECTIVE: To study the feasibility of ArcCheck verification system in dosimetric
      verification for stereotactic radiotherapy (SRT) the stereotactic radiotherapy
      (SRT) with flattening filter free (FFF) model.? Methods: A total of 76 cases
      under SRT treatment plans were introduced into ArcCheck phantom and recalculated.
      Threshold criteria was set as (3%, 3 mm, 10%) or (2%, 2 mm, 10%). The calculated
      dose distribution and the measured dose distribution of ArcCheck phantom were
      compared by means of distance to agree (DTA) and Gamma analysis method
      respectively.? Results: Based on the threshold criteria (3%, 3 mm, 10%), the
      relative and absolute mean pass rates of SRT treatment plans by DTA and Gamma
      analysis were greater than 95%. Based on the threshold criteria (2%, 2 mm, 10%),
      the relative and absolute mean pass rates of SRT treatment plan by DTA and Gamma
      analysis were about 90%. The dose pass rate of Gamma analysis method was slightly
      higher than that of DTA analysis method (P<0.001).? Conclusion: The ArcCheck
      verification system is a rapid and accurate method for SRT dose verification, and
      discrepancies are found in different analysis methods.

PMID- 30197315
TI  - [Nontarget area and threshold selection in 99mTc-DTPA orbital SPECT/CT imaging
      inthyroid associated ophthalmopathy].
AB  - OBJECTIVE: To compare diagnostic value of 4 kinds of target-to-nontarget ratio
      (T/NT), and to choose a better one to assess thyroid associated ophthalmopathy
      (TAO) activity.? Methods: The clinical data were collected for 29 newly-diagnosed
      patients (58 eyes) with TAO who underwent orbital 99mTc-DTPA single photon
      emission computed tomography/computed tomography (SPECT/CT) fusion images
      according to the clinical activity score (CAS). They were divided into an active
      group (18 cases, 36 eyes), an inactive group (11 cases, 22 eyes), and a control
      group (9 cases, 18 eyes). Diagnostic value of orbital/occipital lobe radioactive
      uptake count ratio (T/NT1), orbital/occipital radioactive uptake count ratio
      (T/NT2), orbital/thalamus radioactive uptake count ratio (T/NT3), and
      orbital/cerebellar radioactivity uptake count ratio (T/NT4) were calculated, and
      the CAS of Spearman rank correlation and receiver operating characteristic (ROC)
      curve were analyzed.? Results: T/NT1, T/NT2 and CAS were correlated (r1=0.873,
      r2=0.527; P<0.001), with the better correlation between T/NT1 and CAS and there
      was no correlation between T/NT3, T/NT4 and CAS (r3=0.039, r4=0.090; P>0.05).
      Area under the ROC curve of T/NT1 was 0.860, area under the ROC curve of T/NT2
      was 0.581, and the accuracy for T/NT1 on TAO activity was good. T/NT1=9.74 could
      be used as active threshold for judge of TAO in patients.? Conclusion: There is a
      good correlation between T/NT1 and CAS. TAO activity assessment possesses high
      diagnostic value, and SPECT/CT together with imaging anatomical location is more
      accurate.

PMID- 30197317
TI  - [Clinical value for contrast-enhanced transrectal ultrasound in diagnosis of
      prostate cancer].
AB  - OBJECTIVE: To explore the value for contrast-enhanced transrectal ultrasound
      (CETRUS) in the diagnosis of prostate cancer.? Methods: Prostate biopsy from 207
      cases of suspected prostate cancer were collected between January 2013 and March
      2015. These patients were performed ultrasound-guided prostate biopsy in Central
      Hospital of Changsha. They were randomly divided into a radiography group (n=104)
      and a non-radiography group (n=103) according to the order of treatment.
      Transrectal ultrasonography (TRUS) was the first choice in the 2 groups, and
      CETRUS was conducted in the radiography group. Then, the transrectal biopsy was
      carried out in the 2 groups. The diagnostic value of CETRUS in prostate cancer
      was evaluated by pathological examination, a gold standard.? Results: The
      sensitivity, specificity, and coincidence rates of TRUS in diagnosing prostate
      cancer were 65%, 60.4%, and 62.8%, respectively, while those rates of CETRUS in
      diagnosing prostate cancer were 89%, 78%, and 84%, respectively, with significant
      difference between the above 2 groups (all P<0.05).? Conclusion: The
      sensitivities, specificities, and coincidence rates for CETRUS are superior to
      TRUS in diagnosing prostate cancer, which can provide a clinical basis for the
      diagnosis and differential diagnosis of prostate cancer.

PMID- 30197316
TI  - [Effect of a noise-optimized virtual monoenergetic reconstruction technique on
      dual-energy CT for image quality of inflammatory bowel disease].
AB  - OBJECTIVE: To assess the value of noise-optimized virtual monoenergetic imaging
      (VMI+) reconstruction technique on objective and subjective image quality in
      patients with inflammatory bowel disease (IBD) undergoing abdominal dual-energy
      computed tomography (DECT).? Methods: Datasets from 32 patients (22 men, 10
      women) with IBD, who underwent abdominal DECT, were reconstructed by using the
      standard linearly blended (M_0.6), traditional monoenergetic (VMI) and VMI+
      algorithms in 10-keV intervals from 40-100 keV. Attenuation in IBD lesions was
      measured to perform objective evaluation using signal-to-noise (SNR) and contrast
      to-noise ratios (CNR). Subjective evaluation was performed by 3 independent
      blinded radiologists using 5-point Likert scales. The overall image quality,
      image sharpness, lesion delineation, and image noise were analyzed. ? Results:
      Mean SNR and CNR peaked at 40 keV VMI+ series (SNR 8.28+/-2.34, CNR 5.10+/-2.10)
      and they were significantly higher than those in linearly blended (SNR 5.82+/
      1.44, CNR 1.53+/-0.86) and all VMI series (all P<0.01). Subjective image
      parameter was the highest for the 50 keV VMI+ series regarding overall image
      quality (mean 4.80, all P<0.01). The highest image sharpness scores were observed
      at 40 and 50 keV VMI+ reconstructions (mean 4.14 and 4.25, respectively;
      P=0.415). VMI+ series at 40 keV provided the highest lesion delineation (mean
      4.52, all P<0.01). Image noise was low at the 100 keV VMI+ and VMI series (mean
      4.58 and 4.40, respectively; P>=0.11).? Conclusion: Low-keV VMI+ reconstructions
      improves SNR, CNR, and subjective image quality significantly in patients with
      IBD.

PMID- 30197318
TI  - [Blood flow parameters of posterior cerebral artery in normal pregnancy during
      middle and late stage].
AB  - OBJECTIVE: To study the blood flow parameters for 2 anatomical segments of
      posterior cerebral artery (PCA) in normal singleton fetal.? Methods: The blood
      flow velocity parameters peak systolic velocity (PSV), end diastolic velocity
      (EDV), time-average maximum velocity (TAMAXV), velocity time integral (VTI) and
      resistance parameters systolic peak velocity and end diastolic velocity ratio
      (S/D), pulsatility index (PI), resistance index (RI) for 2 anatomical segments in
      PCA were recorded. The first segment of the PCA (PCAS1) was recorded between the
      origin of PCA and the proximal part of the posterior communicating artery. The
      second segment of the PCA (PCAS2) was recorded at the distal part of the
      posterior communicating artery. The blood parameters in both PCAS1 and PCAS2 were
      analyzed by using Pearson correlation and multiple curves fitting with
      gestational age (GA). Paired student's t test was performed to compare the
      difference in blood parameter between PCAS1 and PCAS2.? Results: The blood flow
      velocity parameters in both PCAS1 and PCAS2 were increased with the GA
      (P<0.0001), with the best fitted curves of Quadratic curve (P<0.0001). There were
      no correlations between resistance parameters in PCA and GA (P>0.05). Resistance
      parameters in PCAS1 were higher than those in PCAS2 (P<0.05).? Conclusion: The
      blood flow velocity parameters in both PCAS1 and PCAS2 are increased with GA. The
      resistance parameters in both PCAS1 and PCAS2 do not change with GA. Study on the
      velocities and resistance in these 3 arterial branches provides a more
      comprehensive evaluation on the process of brain circulation.

PMID- 30197319
TI  - [Association between red blood cell volume distribution width and osteophytes: A
      cross-sectional study].
AB  - OBJECTIVE: To investigate the association between red blood cell volume
      distribution width (RDW) and osteophytes.? Methods: This cross-sectional study
      was conducted in the Department of Health Examination Center of Xiangya Hospital,
      Central South University in Changsha, Hunan Province, China. A total of 8 334
      subjects were included in this study. The severity of osteophytes was graded
      using the criteria of the Osteoarthritis Research Society International (OARSI).
      Osteophytes incident was defined as at least one side of the knee had a
      osteophytes grade >=1. According to the quartiles of the RDW level, the subjects
      were divided into 4 groups. Multivariate logistic regression analysis was used to
      calculate the odds ratio (OR) and the 95% confidence interval (CI) of the knee
      osteophytes incidence between each RDW group and the lowest level group. Tests
      for linear trends were conducted based on logistic regression using a median
      variable of RDW level in each category.? Results: Quartile 1 (Q1), RDW<=9.78; Q2,
      9.78<RDW<=10.70; Q3, 10.70<RDW<=13.10; Q4, RDW>13.10. The multivariable adjusted
      ORs (95%CI) of the prevalence of osteophytes were 1.38 (1.06 to 1.79) in the
      second percentile interval, and 1.27 (0.97 to 1.66) and 1.50 (1.15 to 1.94) in
      the third and fourth percentile interval, respectively. Test for linear trends
      suggested that there was a positive association between the RDW level and the
      risk of knee osteophytes incidence (P=0.019).? Conclusion: The risk of
      osteophytes incidence increases with the increasing RDW levels.

PMID- 30197320
TI  - [Epidemiological characteristics and spatial-temporal clustering analysis on
      pulmonary tuberculosis in Changsha from 2013 to 2016].
AB  - OBJECTIVE: To analyze the epidemic characteristics and to explore the spatial
      temporal clusters of pulmonary tuberculosis (PTB) in Changsha from 2013 to 2016.?
      Methods: Descriptive analysis and space-time permutation scan statistic were used
      to analyze the reported PTB cases in Changsha from 2013 to 2016.? Results:
      Between 2013 and 2016, a total of 17 721 PTB cases were reported in Changsha,
      with annual reported incidence rate at 60.87 per 100 000 population. Males and
      individuals aged 15 to <60 years accounted for higher proportion of PTB cases
      compared to females and other age groups. The number of reported PTB cases
      reached peak from March to May in each year. The space-time permutation scan
      statistic identified one most likely cluster and two secondary clusters of PTB
      cases. The most likely cluster covered most areas of Liuyang City and the North
      east part of Changsha County from October 1, 2013 to February 28, 2014. The first
      cluster occupied 12 towns (streets) in Kaifu District and Changsha County in
      December 2016. The second cluster included four towns (streets) in Yuhua District
      and Tianxin District from March 1 to September 30, in 2013.? Conclusion: Between
      2013 and 2016, significant space-time clusters of PTB cases were identified in
      Changsha. These findings could provide a guide for development of regional
      intervention strategies for PTB control.

PMID- 30197321
TI  - [Biological roles of adenosine deaminase acting on RNA and their relationship
      with human diseases].
AB  - RNA editing, especially A-to-I RNA editing, is a common post-transcriptional
      modification in mammals. Adenosine deaminase acting on RNA (ADAR) is a key
      protein for A-to-I editing, which converts the adenosine group of a double
      stranded RNA to creatinine group by deaminating it, resulting in a change of
      nucleotide sequence. There are 3 types of ADARs (ADAR1, ADAR2, ADAR3) that have
      been found in recent years. The abnormalities of ADARs are closely related to
      many human diseases such as viral infections, metabolic diseases, nervous system
      diseases, and tumors.

PMID- 30197322
TI  - [Research progress of long noncoding RNA in regulating adipogenesis].
AB  - Long noncoding RNA (lncRNA) is once thought to be the genome transcriptional
      "noise". However, it has received considerable attention in the past few years
      and is emerging as potentially important player in biological regulation. Recent
      studies have revealed that increasing number of lncRNA plays pivotal roles in
      regulating the gene expression which involves in the development of the human
      disease. Functions of lncRNA include 3 types of interaction: RNA-RNA, RNA-DNA,
      and RNA-protein, which may participate in gene expression regulation through
      epigenetic modifications, transcriptional regulation, post-transcriptional
      regulation, acting as biological media. Due to the prevalence of obesity and
      related diseases, some attempts have been done to explore the pathogenesis of
      obesity from the field of noncoding RNA. Several lncRNAs have been identified to
      be involved in the regulation of the adipogenesis (white adipose tissue and brown
      adipose tissue) and energy metabolism. In this review, we summarized recent
      advances of lncRNAs to provide a new sight for the mechanism of obesity.

PMID- 30197323
TI  - [Recent progress in smooth muscle autophagy of vascular diseases].
AB  - Autophagy plays a crucial role in maintaining normal structure and vascular
      function in vivo. When stress-relevant stimuli are involved, the increases of
      autophagy can protect vascular smooth muscle cells, promote cell survival, and
      phenotype transformation, as well as reduce calcification. On the contrary, the
      decrease of autophagy can accelerate cell senescence, resulting in structural
      changes and dysfunction of vasomotor and vasodilation. However, excessive
      activation of autophagy can induce the damage of the healthy protein and
      essential organelles, and even lead to autophagic cell death, accelerating the
      progression of vascular disease. Thus, the precise targeting of autophagy opens a
      novel way for treatment of vascular diseases.

PMID- 30197324
TI  - Bosutinib: Valuable therapeutic option for the Bulgarian market.
AB  - Aim of Study: This review aims to highlight that bosutinib represents a valuable
      alternative for patients already treated unsuccessfully with one or more other
      tyrosine kinase inhibitors (TKIs). Chronic myelogenous leukemia (CML) is a
      myeloproliferative neoplasm associated with a specific genetic abnormality
      resulting in a fusion protein with an active tyrosine kinase region. Therefore,
      TKIs were developed as a suitable treatment option. Methods: Full-text articles,
      abstracts, and meta-analysis comparing the efficacy and safety of the five TKIs
      were included in the review. Efficacy of these enhanced therapies is estimated on
      the basis of achievement of a complete cytogenetic response (CCyR) and this
      outcome is an important goal as a surrogate marker for improved survival.
      Results: Bosutinib's efficacy is comparable to that of imatinib in the first-line
      setting and with dasatinib and nilotinib as second-line therapy, while its safety
      profile is distinctly different. Most therapeutic guidelines for CML recommend an
      initiation of therapy with imatinib and application of dasatinib and nilotinib as
      subsequent lines. Conclusion: Bosutinib is generally not recommended despite its
      demonstrated efficacy and manageable toxicity. However, resistance, intolerance,
      specific mutations, as well as disease progression are often the reasons for the
      lack of sufficient response to therapy registered by the lower rates or complete
      absence of CCyR. Treatment options are limited for these patients.

PMID- 30197325
TI  - Assessment of microsatellite instability for screening bladder cancer in high
      risk population.
AB  - Aims: This study aims to determine the diagnostic efficacy of microsatellite
      markers for screening bladder cancer in population at high risk. Materials and
      Methods: A population of 200 people was screened for bladder cancer using a set
      of microsatellite markers. Urine samples were obtained from four different types
      of population groups - Group 1 (healthy population group), Group 2 (current
      smokers with a smoking history of more than 10 years), Group 3 (bladder cancer
      group), and Group 4 (bladder cancer group who were former smokers with a history
      of more than 10 years). Polymerase chain reaction (PCR) was performed to amplify
      microsatellite sequences at D9S63, D9S156, and D9S283. PCR products were
      separated on 1.8% agarose gel and were scanned using ultraviolet
      transilluminator. Results: In Group 2 (high-risk population group, mainly current
      smokers with a history of more than 10 years), microsatellite alterations were
      found in 36 out of 50 people. We observed microsatellite alterations in 38 out of
      50 people in Group 3 (bladder cancer group) and in 39 out of 50 people in Group 4
      (bladder cancer group, mainly former smokers with a history of more than 10
      years). The sensitivity of this test in Group 2, Group 3, and Group 4 was found
      to be 72%, 76% and 78%, respectively. The specificity of this test in each group
      was found to be 90%. Conclusion: Using these set of microsatellite markers,
      medium sensitivity and high specificity were reported for this test. The current
      findings suggest that a set of microsatellite markers (D9S63, D9S156, and D9S283)
      can be used to detect bladder cancer in high-risk population.

PMID- 30197326
TI  - Comparative analysis of oral rinse-based cytology and conventional exfoliative
      cytology: A pilot study.
AB  - Background: Oral exfoliative cytology is a novel technique of using cells to
      detect dysplastic changes in the oral cavity in potentially malignant disorders
      and malignant oral lesions in resourced challenged areas. The aim of this study
      was to compare specimen adequacy and cellular clarity between oral rinse-based
      smears and conventional smears in normal controls, histologically confirmed and
      clinically diagnosed squamous cell carcinoma, and oral leukoplakia. For many
      years, oral rinse-based cytology has been used to detect candidal colonization in
      microbiology. Emphasis has been placed to detect changes in oral rinse-based
      cytology. From this research and development, oral rinse-based cytology has
      evolved as a method of preparing samples for examination in cytopathology.
      Materials and Methods: Oral exfoliated cells from 10 cases of smears of
      potentially malignant disorders (oral leukoplakia), 10 cases of histologically
      confirmed and clinically diagnosed squamous cell carcinoma, and 10 controls with
      healthy mucosa were taken. Smears were stained with the Papanicolaou stain and
      were examined independently by two different oral pathologists. The results were
      compared to assess four parameters such as nuclear cytoplasmic ratio, sample
      adequacy, cellular distribution, and cellular clarity in both the smears. The
      results were then analyzed with SPSS (version 20) software using the descriptive
      statistics such as mean and standard deviation and inferential statistics such as
      t-test and one-way ANOVA. The level of significance was set at 5%. Results: Oral
      rinse-based cytology was significantly more efficient than conventional
      exfoliative cytology in terms of cellular clarity (P < 0.001), cellular
      distribution (P < 0.001), and sample adequacy (P < 0.001). Conclusion: Oral rinse
      based cytology shows overall improvement in cellular clarity, sample adequacy as
      compared to traditional exfoliative cytology.

PMID- 30197327
TI  - Lomustine, cytarabine, cyclophosphamide, etoposide - An effective conditioning
      regimen in autologous hematopoietic stem cell transplant for primary refractory
      or relapsed lymphoma: Analysis of toxicity, long-term outcome, and prognostic
      factors.
AB  - Background: High-dose chemotherapy followed by autologous hematopoietic stem cell
      transplant (HSCT) is the treatment of choice for patients with relapsed and
      refractory (RR) lymphoma. We analyzed toxicity and long-term outcome with
      lomustine, cytarabine, cyclophosphamide, etoposide (LACE) conditioning in
      patients with primary refractory or relapsed lymphoma undergoing autologous
      transplant. Materials and Methods: One-hundred patients with primary refractory
      (23), chemotherapy sensitive relapse (74) or RR (3) Hodgkin lymphoma (HL - 70
      patients), and non-HL (NHL - 30 patients) underwent HSCT with LACE (lomustine 200
      mg/m 2 day-7, etoposide 1000 mg/m 2 day-7, cytarabine 2000 mg/m 2 day-6 to day-5,
      and cyclophosphamide 1800 mg/m 2 day-4 to day-2) conditioning between November
      2007 and December 2013. At transplant, 68 patients were in complete remission
      (CR), 29 in partial remission, 2 had stable disease, and 1 had progressive
      disease. Patients were followed up for development of transplant-related
      toxicities and long-term survival outcome. Results: The incidence of grades 3-4
      oral mucositis and grades 3-4 diarrhea was 8% and 4%, respectively. Median days
      to myeloid and platelet engraftment were 10 and 13. Transplant-related mortality
      was 7%. At median follow-up of 3 years, probability of overall survival (OS) and
      progression-free survival (PFS) at 3 years was 70% and 58% in entire cohort, 78%
      and 62% in HL and 51% and 46% in NHL subgroup, respectively. International
      Prognostic Score (IPS) >2 at relapse prognosticated for poor OS (P = 0.002) and
      PFS (P < 0.001) in HL subgroup. Positron emission tomography positivity
      pretransplant (HL subgroup) and at day + 100 (NHL subgroup) predicted for poor
      survival. Conclusion: We conclude that LACE is effective and well-tolerated
      conditioning regimen. IPS at relapse is the most important prognostic factor in
      HL transplant.

PMID- 30197329
TI  - The anti-cancer efficacies of diffractaic, lobaric, and usnic acid: In vitro
      inhibition of glioma.
AB  - Aims: Glioblastoma multiforme (GBM) shows the most aggressive invasion among
      primary brain tumors. In spite of the standard therapy methods such as surgery,
      radiotherapy, and chemotherapy, the mortalities are high in GBM patients owing to
      side effects. Some lichen secondary metabolites that have many bioactive
      functions exhibited anti-cancer efficacy toward many cancer types. The present
      study was undertaken to investigate proliferation change, oxidative status and
      DNA damage potentials of human U87MG-GBM, and primary rat cerebral cortex (PRCC)
      cells exposed to three lichen secondary metabolites. Materials and Methods:
      Different concentrations of lichen secondary metabolites including diffractaic
      acid (DA), lobaric acid (LA), and (+)-usnic acid (UA) were used for the
      treatments. PRCC cells were obtained from Sprague Dawley(r) rats. U87MG cell line
      was preferred as GBM cells. Results: The results showed that lactate
      dehydrogenase and 8-hydroxy-2'-deoxyguanosine levels increased in PRCC and U87MG
      cells in a clear dose-dependent manner. Inhibitory concentration 50% (IC50)
      values of LA, DA, and UA were calculated as 9.08, 122.26, 132.69 mg/L for PRCC
      cells and 5.77, 35.67, 41.55 mg/L for U87MG cells, respectively. Concentration of
      10 mg/L of DA and UA demonstrated high anti-oxidant capacity on healthy PRCC
      cells. Conclusions: Overall, obtained data indicated that LA was highly toxic on
      GBM and PRCC cells. However, DA and then UA had high anti-oxidant capacity on
      PRCC cells. These results suggest that further studies that will be held on LA
      may play a critical role in GBM treatment.

PMID- 30197328
TI  - Correlation of serum lactate dehydrogenase and alkaline phosphatase in different
      histological grades of head and neck squamous cell carcinoma and premalignant
      lesions.
AB  - Context: Head neck cancer (HNCA) in North-East India accounts for 54.48% cancers
      at all sites, one of the highest in the country. Increased serum lactate
      dehydrogenase (LDH) activity is considered as a marker of cellular necrosis while
      serum alkaline phosphatase (ALP) is recognized as an important marker of
      induction of tumor cell differentiation. Considering the importance and need of
      biomarker in HNCA and there being no previous study on tumor markers from this
      highly prevalent region, we intended to examine the role of serum LDH and ALP in
      head and neck squamous cell carcinoma (HNSCC) and epithelial precursor lesions
      (EPLs) and also to find their correlation with the different histological grades
      of tumor. Materials and Methods: This is a prospective observational study on
      patients with HNSCC and precancerous lesions attending Department of ENT of a
      Teaching Hospital. Serum LDH and ALP was measured in HNSCC, EPL and control
      groups and the results were statistically analyzed and compared using analysis of
      variance, Pearson correlation coefficient, and sensitivity-specificity analysis.
      Results: Serum LDH was found to be a significant marker of HNSCC. Total serum LDH
      level was high in both premalignant and HNSCC cases. There was a significant
      correlation between serum LDH and grades of HNSCC showing highest levels of
      expression in moderately differentiated SCC. Elevated serum LDH was also seen in
      erythroleukoplakia, leukoplakia, and verrucous lesion, but serum ALP levels were
      not significant. Conclusions: This is the first study from this highly prevalent
      region of HNCA showing that serum LDH could be regarded as a biomarker for
      malignant and premalignant conditions of the head and neck.

PMID- 30197330
TI  - Immunohistochemical study of the expression of human chorionic gonadotropin-beta
      in salivary gland tumors.
AB  - Background and Objectives: Human chorionic gonadotropin-beta (hCGbeta) is a
      hormone glycoprotein usually secreted by trophoblastic cells in early pregnancy
      and helps in growth and development of the embryo. While many trophoblastic and
      nontrophoblastic malignancies express elevated levels of hCGbeta in serum,
      increased immunohistochemical reactivity has also been reported in malignant and
      aggressive tumors, thus serving as a marker. As limited studies exist on tumors
      of the oral- and para-oral region, it prompted us to observe the
      immunohistochemical expression of hCGbeta in salivary gland tumors. Materials and
      Methods: A total of 21 cases of salivary gland tumors - 16 cases of
      mucoepidermoid carcinoma (MEC), adenoid cystic carcinoma (ACC), and five cases of
      pleomorphic adenoma - were included in the study. The sections were subjected to
      immunohistochemical procedures using hCGbeta antigen. The degree of intensity and
      distribution of hCGbeta immunostaining was assessed. Results: One case of each
      (12.5%) MEC and ACC showed positive staining, and no staining was observed in the
      pleomorphic adenoma. Conclusion: The presence of hCGbeta positive tumor cells
      appears to potentially reflect the aggressive behavior of MEC and ACC.

PMID- 30197332
TI  - Immunohistochemical expression of TWIST in oral squamous cell carcinoma and its
      correlation with clinicopathologic factors.
AB  - Background and Objectives: TWIST is a transcription factor that plays a key role
      in the development of primary tumor to metastatic stage of cancer. It is an
      inhibitor of E-cadherin in epithelial-to-mesenchymal transformation process
      (epithelial-mesenchymal transition). Few studies are available on the use of
      TWIST as a goal in molecular-targeted therapy. The aim of this study was to
      evaluate of TWIST expression in oral squamous cell carcinoma (OSCC) and its
      correlation with clinicopathologic factors. Materials and Methods: In this cross
      sectional study, immunohistochemical staining was for TWIST performed on 30
      paraffin-embedded blocks of OSCC. Furthermore, thirty paraffin-embedded blocks of
      normal oral mucosa with minimum inflammation from the clinical and
      histopathologic aspects were selected. Staining intensity and percentage of
      stained cells from nuclear and cytoplasmic aspects were ranked in epithelial
      cells. TWIST expression and correlation with clinicopathologic factors were
      analyzed using Cox regression and Chi-square tests. Results: TWIST expression in
      OSCC was significantly increased compared to oral normal mucosa. Nuclear
      expression of TWIST in OSCC was significantly associated with clinical stage (P =
      0.01) and lymph node metastasis (P = 0.007). Cytoplasmic expression of TWIST in
      OSCC was not associated with any clinicopathological factors. Conclusion: The
      results support the role of TWIST in carcinogenesis, development of OSCC, and its
      metastasis to lymph nodes.

PMID- 30197331
TI  - Health-related quality of life: Impact of surgery and treatment modality in
      breast cancer.
AB  - Background: Breast cancer is the most common malignancy among women leading to
      serious sequelae on the health-related quality of life (HRQOL). Materials and
      Methods: This is a cross-sectional study. The Arabic version of EORTC QLQ-C30
      (version 3) and EORTC QLQ-BR23 questionnaire was administered to a random sample
      of 172 Egyptian women with breast cancer. One hundred and nineteen patients had
      modified radical mastectomy (MRM) and 53 had breast conservative surgery (BCS).
      Results: The mean age was 50.32 years (+/-standard deviation [SD] = 8.54) with a
      mean period of 4.75 years (+/-SD 3.33) from surgery. The global health was poor
      (28.38 +/- 11.7, 95% confidence interval [95% CI]: 30.71). Among the functional
      scales of QLQ-C30, social functioning scored the highest (87.91 +/- 17.92, 95%
      CI: 91.64) whereas emotional functioning scored the lowest (59.61 +/- 24.96, 95%
      CI: 64.66). The most distressing symptom on the symptom scales of QLQ-C30 was
      financial impact followed by fatigue and pain (mean: 57.87, 39.43, and 36.44).
      Using the disease-specific tools, it was found that body image and sexual
      functioning scored the lowest (mean 74.51 +/- 13.21 and 74.45 +/- 14.89, 95% CI:
      77.27 and 77.55), respectively. On the symptom scale, arm symptoms scored the
      highest with a mean of 32.35 +/- 23.22 (95% CI: 37.19). MRM patients had more
      favorable global health status and body image among the functional scale (P =
      0.011, 0.027) due to social and religious issues. The functional scale was better
      in BCS with significant role function (P = 0.004). In the symptom scale, fatigue,
      pain, systemic side effects, and arm symptoms were statistically significant
      better in the BCS (P = 0.004, 0.006, 0.002, and 0.003, respectively). Conclusion:
      Egyptian breast cancer survivors reported lower overall global QOL. HRQOL is
      better in BCS in spite of good global health and body image in MRM.

PMID- 30197333
TI  - Expression of Numb and Gli1 in malignant pleural mesothelioma and their clinical
      significance.
AB  - Aim of Study: Malignant pleural mesothelioma (MPM) is a highly lethal and
      refractory to multimodal treatment tumor. Numb is considered as a tumor
      suppressor playing critical roles in determining cell fate and has been shown to
      target the oncogenic transcription factor Gli1 for Itch-dependent ubiquitination,
      resulting in suppression of the oncogenic sonic hedgehog signaling in
      medulloblastoma. This study was designed to analysis the role of Numb and Gli1 in
      MPM. Materials and Methods: Tissues of 61 MPM patients and 22 normal pleura as
      control were investigated. Numb and Gli1 expression were evaluated by
      immunohistochemistry. The associations with clinical and pathological parameters
      of the two markers were statistically analyzed, and the correlation between them
      was also demonstrated. Results: The expression levels of Numb with nuclear Gli1
      exhibited a significant inverse correlation (r = -0.361 P < 0.05). In addition,
      Numb has an inverse correlation with ki-67 labeling index (P < 0.05), and nuclear
      Gli1 was found in associated with the tumor International Mesothelioma Interest
      Group-stage (P < 0.05). The overall survival was influenced by the expression of
      Numb (P < 0.05) and histological subtype (P < 0.05), further regression analysis
      showed that only histological subtype has a prognostic influence on survival (P <
      0.05). Conclusion: The results provide new evidence of Numb and Gli1 on the
      clinical characteristics of MPM, which may be helpful in clinical diagnosis and
      targeted therapy. Further research with larger sample size is needed.

PMID- 30197334
TI  - Speckle-type POZ protein as a diagnostic biomarker in renal cell carcinoma.
AB  - Background: Renal cell carcinoma (RCC) is the most common kidney neoplasm and
      requires an early diagnosis because of poor response to conventional cancer
      treatments. However, till date, there is no reliable tumor marker available for
      the diagnosis of RCC. Objective: The aim of the study was to evaluate the
      expression of speckle-type POZ protein (SPOP) as a biomarker in patients with
      RCC. Materials and Methods: Blood samples were collected from fifty patients with
      RCC and ten healthy controls. Tumor tissue samples were obtained from nephrectomy
      specimen. Adjoining normal renal parenchyma of these fifty patients and eight
      normal renal tissue samples from normal kidney served as controls. Reverse
      transcriptase-polymerase chain reaction assay was performed for SPOP and
      mammalian target of rapamycin expression. Results: SPOP was significantly
      increased in blood of patients with RCC as compared to controls (0.754 +/- 0.32
      vs. 0.224 +/- 0.14; P < 0.001). Twenty-two patients (44%) had SPOP value more
      than mean + 2 standard deviation (SD) of controls. In RCC tissue, 42 (84%)
      patients had increased expression of SPOP more than 0.523 (mean + 2 SD value of
      SPOP expression in controls). SPOP expression was high in blood of 60% patients
      and in tumor tissue of 90% patients with clear cell RCC. SPOP was higher in high
      grade and high stage of RCC. Conclusions: Our result suggests that SPOP
      expression in blood might have a sensitivity that is low for routine diagnostic
      use and for screening for RCC. However, SPOP could be a potential tissue
      diagnostic biomarker in RCC.

PMID- 30197335
TI  - Comparison of microvessel density using CD34 and CD105 in oral submucous fibrosis
      and its correlation with clinicopathological features: An immunohistochemical
      study.
AB  - Objectives: To compare immunohistochemical expression of CD34 and CD105 in oral
      submucous fibrosis (OSF) and normal oral mucosa (NOM) and correlate with
      clinicopathological features of OSF. Materials and Methods: Total of thirty
      clinically diagnosed and histologically confirmed cases of OSF and 15 NOM were
      included in the study. Tissues sections were immunostained using CD34 and CD105
      antibodies. Results: Twenty-eight cases (93.33%) were positive for CD34, and only
      12 cases (40%) were positive for CD105 in OSF. In NOM all cases were positive for
      CD34 and only one case was positive for CD105. CD34 and CD105 significantly
      expressed in moderately advanced OSF when compared to very early, early, and
      advanced cases. It was found that the microvessel density (MVD) in NOM was
      significantly higher as compared to OSF and MVD decreased with advanced OSF. MVD
      was higher in CD34 when compared to CD105. MVD decreased with disease progression
      in OSF using both the markers. Conclusion: The role of CD34 in determining the
      premalignant nature of OSF could not be ascertained, since all endothelial cells
      were positive for CD34, whereas CD105 appeared to be more specific as it is
      associated with hypoxia-induced angiogenesis which is occurring in OSF due to
      hyalinization suggesting, CD105 to be more specific marker to determine
      neoangiogenesis in OSF. Thus further follow-up study of the cases positive for
      CD105 is required to determine the true nature of angiogenesis in OSF patients.

PMID- 30197336
TI  - Clinical significance of standardized uptake values in thyroid incidentaloma
      discovered by F-18 fluorodeoxyglucose positron emission tomography/computed
      tomography.
AB  - Aim of Study: While using F-18 fluorodeoxyglucose (FDG) positron emission
      tomography computed tomography (PET/CT) for other than thyroid disease, an
      increased frequency of incidentally discovered areas of focally or diffuse
      increased uptake within the thyroid gland can be seen. We aimed to find the focal
      thyroid FDG uptake and compare the maximum standardized uptake value (SUVmax)
      results with cytology and histology results. Materials and Methods: We examined
      PET scan reports for all patients undergoing FDG PET/CT investigation over a 10
      year period in a single center. Twelve thousand seven hundred and ninety-six
      patients underwent FDG PET/CT scanning in one PET/CT unit. Within this group, 526
      patients had diffuse, focal, or multifocal FDG uptake. About 305 of 526 patients
      (57.9%) showed diffuse FDG uptake and 221 (42%) showed focal uptake on thyroid
      gland. Results: The malignant group thyroid nodule sizes were between 8 and 39 mm
      (21.1 mm average, standard deviation [SD] +/-7.3) on ultrasonography (USG)
      examination. These nodules have SUVmax values between 2.3 and 31.2 (average 8.8
      SD +/- 5.7). Benign group thyroid nodule sizes were between 5 and 46 mm (average
      18.3 mm, SD +/- 5.8) on USG examination. There were no significant correlations
      between SUVmax of the incidental focal thyroid lesions seen on FDG PET/CT and
      fine needle aspiration biopsy results. Conclusion: There is a relatively high
      possibility of a malignant lesion in thyroid incidentaloma. FDG uptake of these
      lesions is not a useful tool in absolute discrimination between malignancy and
      benign lesion. The presence of primary or secondary malign lesion is diagnosed in
      34.1% of the patients who are found to have incidental focal FDG uptake within
      thyroid gland in PET/CT scans, but we suggest that the thyroid incidentalomas
      detected on FDG PET/CT should be further examined with USG and scintigraphy.

PMID- 30197337
TI  - The correlation of prognostic biomarkers (Ki-67, Bcl-2, HIF-1alpha, cyclin D1)
      with metabolic tumor volume measured by F-FDG PET/CT inlaryngeal cancer.
AB  - Objectives: To investigate the correlation between tumor stage, Ki-67, Bcl-2,
      hypoxia inducible factor-1alpha (HIF-1alpha), cyclin D1 and metabolic tumor
      volume (MTV), total lesion glycolysis (TLG), maximum standardized uptake value
      (SUVmax) measured by 18F fluorodeoxyglucose positron emission tomography/computed
      tomography (FDG PET/CT) in patients diagnosed with laryngeal cancer. Patients and
      Methods: In this study, included 25 consecutive laryngeal cancer patients (2
      women, 23 men) diagnosed and treated in the Otorhinolaryngology Department of our
      tertiary care center. All cases underwent 18F FDG PET/CT and SUVmax, mean
      standardized uptake value, MTV, and TLG values were calculated. Tumor staging was
      made and immunohistochemical staining was carried out for Ki-67, Bcl-2, HIF
      1alpha and cyclin D1. Results: Eight (32%) patients had glottic laryngeal cancer,
      6 (24%) had supraglottic laryngeal cancer and 11 (44%) had transglottic laryngeal
      cancer. Cyclin D1 was significantly correlated with MTV (r = 0.45, P = 0.03), TLG
      (r = 0.492, P = 0.01) and T-stage (r = 0.483, P = 0.02). Bcl-2 was significantly
      correlated with SUVmax (r = -0.41, P = 0.05) and tumor stage (r = -0.442, P =
      0.03). MTV and TLG are significantly correlated with nodal stage (r = 0.422, P =
      0.04, r = 0.419, P = 0.04), while TLG (r = 0.403, P = 0.05) and SUVmax (r =
      0.440, P = 0.03) were correlated with tumor stage. Conclusion: Our results
      indicated that biomarkers such as cyclin D1 and Bcl-2 were correlated with
      measures such as MTV, TLG, and SUV in 18F-FDG PET/CT. Integrative and combined
      evaluation of biomarkers and imaging data derived from 18F-FDG PET/CT are
      important for staging and appropriate management of patients with laryngeal
      cancer.

PMID- 30197338
TI  - Incidence of second primary malignant neoplasm in Malwa region of central India.
AB  - Background: Advancement in diagnostic and therapeutic modalities lead to
      increased cancer survivors who have 20% higher risk of developing second primary
      malignancy (SPM). Aim: To look for the incidence, epidemiological factors,
      treatment-related factors, and common risk factors responsible for the
      development of the SPM in Malwa region. Materials and Methods: Records of 7709
      patients who visited the Department of Oncology between May 2008 and August 2015
      were analyzed and looked for the presence of SPM based on Warren and Gates
      criteria for head and neck and International Agency for Research on Cancer
      definition for other sites. Data pertaining age at diagnosis of each tumor,
      gender, site, histology, the duration between primary and secondary tumors,
      treatment received for each malignancy, smoking and drinking habits, and
      metastasis sites were recorded. Results: Of 7709 patients, 56 developed SPM (11
      synchronous and 45 metachronous) with an overall incidence of 0.726%. For
      metachronous SPM, the interval of 10-312 months was observed, with a mean time of
      103.32 months (standard deviation 65.9 months). About 71.42% patients with SPM
      belonged to fifth, sixth, and seventh age decade. The median age of diagnosis for
      the second primary neoplasm was 57 years (range: 34-85 years). Maximum SPM were
      observed among head and neck tumors (33.93%) followed by breast (26.78%). The
      most common sites for SPM are head and neck (32.14%) followed by digestive system
      (19.64%). Breast as the first or the second location was seen associated with
      almost all systems. For the treatment of first primary, six received surgery,
      three received chemotherapy (CT), one received radiotherapy (RT) alone, and rest
      46 patients received combined modality. For the treatment of SPM, 37 patients
      received combined modality, ten received CT, three with RT, and two with surgery
      while four patients received no treatment. Thirty-two patients had habits of
      tobacco, smoking and alcohol intake with twenty patients continued these after
      treatment for the first primary neoplasm. Conclusions: Patients with breast and
      head and neck cancer have a higher risk of developing SPM. The possibility of SPM
      should be considered and excluded during pretreatment evaluation and during
      follow-up of treated cancer patients.

PMID- 30197339
TI  - Comparison of dosimetric parameters of volumetric modulated arc therapy and three
      dimensional conformal radiotherapy in postmastectomy patients with carcinoma
      breast.
AB  - Objective: Our study was undertaken to compare the dosimetric parameters of
      volumetric modulated arc therapy (VMAT) and three-dimensional conformal
      radiotherapy (3DCRT) in postmastectomy patients with left-sided carcinoma breast.
      Study Design: This was a hospital-based cross-sectional study. Materials and
      Methods: Thirty plans were generated - VMAT with two partial arcs and field in
      field tangential 3DCRT plans. Results: In the 3DCRT plans, planning target volume
      (PTV) dose coverage was 2% higher compared with the VMAT plan 98.21 +/- 1.79
      versus 96.30 +/- 2.62 (P = 0.028). The conformity index was better for the 3DCRT
      plan (0.97 vs. 0.95; P = 0.022), while the homogeneity index was worse for the
      VMAT plans (0.16 vs. 0.23; P = 0.057). However, the organ at risk sparing was
      better with the VMAT plans when compared to the 3DCRT plans. This was
      particularly relevant for the higher doses. The V20 Gy (34.94 vs. 24.42), V30 Gy
      (32.32 vs. 16.19), and V40 Gy (28.23 vs. 8.03) for the lung were significantly
      higher for the 3DCRT plans when compared to VMAT plans (P = 0.000). Similarly,
      the V20 Gy (29.88 vs. 12.79), V30 Gy (27.25 vs. 4.94), and V40 Gy (24.58 vs.
      1.47) for the heart was significantly higher for the 3DCRT plans when compared to
      the VMAT plans (P = 0.000). The V5 Gy for lung (77.86 vs. 47.38) and heart (76.18
      vs. 39.36) was significantly higher for the VMAT plans when compared to the 3DCRT
      plans (P = 0.000). Conclusion: VMAT is dosimetrically superior to the field-in
      field 3DCRT for left-sided breast cancer patients owing to its comparable PTV
      coverage and better sparing of heart and lung.

PMID- 30197340
TI  - Oxaliplatin treatment and peripheral nerve damage in cancer patients: A Polish
      cohort study.
AB  - Introduction: Oxaliplatin-induced neurotoxicity is the single main dose-limiting
      factor in the treatment of colorectal cancer. The degree of neurotoxicity may be
      either acute and reversible or observed as cumulative and chronic peripheral
      nerve damage leading to peripheral neuropathy (PNP), walking difficulties,
      extremity hypersensitivity, tingling and numbness, and increased pain sensation.
      Aim: The aim of this paper is to determine and compare the ratio of clinical
      versus subclinical PNP cases in colorectal patients who underwent oxaliplatin
      treatment. Materials and Methods: Thirty-two colorectal cancer patients were
      enrolled in the study. Patients received chemotherapy either as folinic acid and
      5-fluorouracil and oxaliplatin or capecitabine and oxaliplatin regimen.
      Electroneurophysiological tests were performed before the treatment and after the
      4th cycle when the risk of peripheral nerve damage increases. All patients were
      subject to a standard neurological examination and a semi-structured
      questionnaire interview. Results and Discussion: Following oxaliplatin treatment,
      21 (66.6%) of all patients presented neurological symptoms and/or
      electrophysiologically measured signs of PNP; of those, 7 patients (33.4%)
      displayed only electrophysiological changes and the remaining 14 patients (66.6%)
      presented fully symptomatic PNP - 4 patients were new neuropathy cases while the
      other 10 patients were previously diagnosed with PNP and showed signs of further
      neuronal deterioration and progressing sensory and motor dysfunction. Conclusion:
      Our study lays ground for further larger scale longitudinal studies on
      oxaliplatin neurotoxicity and its prevention. We believe that early diagnosis of
      oxaliplatin-induced neurotoxicity is essential in the prevention of irreversible
      nerve damage and should be prioritized when assessing and evaluating treatment so
      that adequate adjustment may be made.

PMID- 30197341
TI  - Imaging features of Ewing's sarcoma: Special reference to uncommon features and
      rare sites of presentation.
AB  - Context: Ewing's sarcoma (EWS) commonly involves long bones with a permeative
      pattern of bone destruction and aggressive interrupted periosteal new bone
      formation. However, radiological features show wide variation and some
      presentations are uncommon, leading to diagnostic confusion. This study is aimed
      at studying the imaging features of proven EWS and highlight the uncommon
      features and rare sites of presentation. Materials and Methods: The imaging
      findings of 100 consecutive histopathologically proven EWS were analyzed
      retrospectively. All uncommon presentations with respect to age and site and
      morphology of lesion were observed. Results: Most of the patients were below 20
      years of age and 8% were younger than 5 years. Other than long bones, ribs, and
      pelvis, other sites considered to be rare and were noted in 25%. Extraosseous
      site involvement was 11%. Uncommon features included epiphyseal involvement (4%),
      sclerosis (4%), expansion of bone (8%), sunray spiculation (10%), calcification
      in soft tissue (8%), saucerization (4%), pathological fracture (5%), fluid-fluid
      level (2%), vertebra plana (2%), and lesion crossing the joint (13%).
      Conclusions: The uncommon observations included incidence in children <5 years
      (8%) and occurrence in craniofacial bones, spine, scapula, and clavicles and in
      extraosseous sites such as retroperitoneum, adrenals, or extremity. Uncommon
      findings included epiphyseal involvement, sclerosis, saucerization, calcification
      in soft tissue component, and pathological fracture and lesion crossing the
      joint.

PMID- 30197342
TI  - Synergistic effect of temozolomide and thymoquinone on human glioblastoma
      multiforme cell line (U87MG).
AB  - Aims: Temozolomide (TMZ) is an alkylating agent used for glioblastoma multiforme
      (GBM) treatment. Nevertheless, resistance to TMZ is a major obstacle to
      successful treatment of this cancer. The aim of the present study was to
      investigate the effects of TMZ and thymoquinone (TQ) on U87MG cell line.
      Materials and Methods: The effect of TMZ and/or TQ on viability and invasion
      potential of U87MG cells was evaluated using various techniques including 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, lactate dehydrogenase
      activity, cell invasion, migration, and adhesion assays. Enzyme-linked
      immunosorbent assay and polymerase chain reaction were used to study the
      expression and secretion of matrix metalloproteinases (MMPs). Results:
      Combination of TMZ and TQ had a synergistic cytotoxic effect on U87MG cells. TMZ
      and/or TQ significantly reduced the potential of U87MG cells invasion. In
      addition, after treating with TMZ and/or TQ, there was a decrease in the levels
      of matrix matrix metalloproteinase 2 nad 9 (MMP 2 and 9) expression and secretion
      in U87MG cells. Conclusions: The combination of TMZ and TQ may emerge as a
      promising strategy for the successful treatment of GBM.

PMID- 30197343
TI  - Evaluation of the photon dose calculation accuracy in radiation therapy of
      malignant pleural mesothelioma.
AB  - Background: Photon dose distribution of malignant pleural mesothelioma (MPM) in
      matched photon-electron technique is influenced by media inhomogeneity, lateral
      electronic disequilibrium at interfaces and narrow field. These may influence the
      dose calculation accuracy, calculated by treatment planning systems (TPS). This
      study aimed to evaluate the dose calculation accuracy of TiGRT TPS in radiation
      therapy of MPM. Materials and Methods: 18 MV photon beams of ONCOR Siemens linear
      accelerator was simulated using EGSnrc Monte Carlo (MC) code. Data of four
      patients were used to compare TPS and MC results in different regions included:
      Open and in-field, under shied and out of field regions. Results: Compared to MC
      results, the TPS overestimated the pleura dose coverage (90% of prescribed dose)
      about 3-12 mm, and also it overestimated the dose in under the shielded regions
      of lung (4-74%). While the TPS underestimated the dose profile width about 1-16
      mm in low dose region (<50% prescribed dose) as well as the out of field region
      dose (4-100%). Conclusions: Results showed that TPS underestimated the dose in
      out of field and overestimated the dose in under the shielded regions. Unlike MC
      measurements, TPS calculation showed adequate pleural dose coverage. Based on the
      results, MC calculation can be used in matched photon-electron beam radiation
      therapy of MPM to modify the TPS photon dose calculations in the presence of
      heterogeneity, interfaces, and shield in MPM radiotherapy.

PMID- 30197344
TI  - Fusion of k-Gabor features from medio-lateral-oblique and craniocaudal view
      mammograms for improved breast cancer diagnosis.
AB  - Context: Computer-aided diagnosis (CAD) combining mammographic features from
      cranio-caudal (CC) and medio-lateral-oblique (MLO) views improve the diagnostic
      performance of breast cancer. This could help doctors incorrect diagnosis at the
      earlier stage thereby reducing mortality. Aim: The aim of this study is to
      propose a breast cancer diagnostic technique for improving the diagnostic
      accuracy and reducing the false positive rate by fusing mammographic features
      from CC and MLO views. Settings and Design: The MLO and CC view mammograms of
      same patients must be used to extract k-Gabor features and then fused to form a
      single feature vector. Subjects and Methods: Mammograms from the digital database
      for screening mammography (DDSM) and INbreast datasets are collected. k-Gabor
      features extracted from both MLO and CC view mammograms are fused serially and
      reduced by principal component analysis (PCA) or genetic algorithm. The reduced
      features are classified using a multi-layer perceptron feed forward neural
      network with backpropagation learning algorithm. Statistical Analysis Used:
      Various relevant performance metrics such as accuracy, sensitivity, specificity,
      discriminant power, Mathews correlation coefficient (MCC), F1 score and Kappa are
      used to analyze the classification results. Results: The accuracy, sensitivity,
      specificity, discriminant power, MCC, F1 score, and Kappa obtained as 92.5%, 93%,
      91.8%, 1.198, 0.845, 0.936, and 0.845, respectively, for DDSM. For INbreast, the
      above specified metrics are 87.5%, 90.9%, 85.7%, 0.980, 0.741, 0.833, and 0.734,
      respectively. The results show 4.4%, 4.3%, and 9.4% improvements in accuracy,
      sensitivity, and specificity, respectively, compared to the previous works.
      Conclusions: Detailed analysis of the results implies that the serial fusion of k
      Gabor features extracted from MLO and CC views with PCA reduction in CAD
      significantly improves the diagnostic performance.

PMID- 30197345
TI  - Comparative expression of caspases and annexin V in benign and malignant ovarian
      tumors.
AB  - Aim of Study: Ovarian cancer (OC) leads to high mortality rate if diagnosed at
      late stage. The aim of the present study was to increase the survival rate by
      early disease diagnosis. Materials and Methods: A total of 21 females were
      divided into three groups. The control (n = 3), benign (n = 8), and malignant
      group (n = 10). We used flow cytometry to analyze cell cycle, caspase-3, -8, and
      annexin V. Results: The results showed that the annexin V expressed in malignant
      group more than benign and normal groups with (P = 0.000 and P = 0.007),
      respectively. Caspase-3 and 8 expression decreased in benign and malignant group
      than in normal group (P = 0.012 and P = 0.007), respectively. Furthermore, sub-G1
      apoptosis level decreased statistically significant in benign and malignant group
      than in normal group (P = 0.012 and P = 0.007), respectively. These data showed
      that (S phase) level had statistically significant increase in malignant group (P
      = 0.007) than the control group and marked statistically significant decrease (P
      = 0.000) in benign group than malignant group. This study explained changes in
      sub-G1 apoptosis for benign group increase statistically significant (P = 0.003)
      than malignant group level. Conclusion: Caspase-3 and -8 and annexin V may serve
      as diagnostic markers in OC, also explained that the decrement in control of the
      S phase in the cell cycle may considered one of the significant factors in the
      development of ovarian tumors.

PMID- 30197346
TI  - Prognostic significance of pretreatment sodium levels in patients of nonsmall
      cell lung cancer treated with pemetrexed-platinum doublet chemotherapy.
AB  - Background: Recent studies have shown pretreatment sodium level to be a
      predictive and prognostic marker in nonsmall cell lung cancer (NSCLC) patients
      treated with erlotinib. The objective of this study was to evaluate the
      prognostic significance of pretreatment sodium levels on progression-free
      survival (PFS) and overall survival (OS) in patients of NSCLC treated with
      pemetrexed-platinum doublet chemotherapy. Patients and Methods: Stage IIIb/IV
      NSCLC patients aged >=18 years for whom baseline serum sodium level was available
      were included in this retrospective study. All patients received standard
      pemetrexed-cisplatin/carboplatin doublet for six cycles followed by maintenance
      pemetrexed till progression. Electronic medical record database of our hospital
      was used to retrieve demographic data, pretreatment sodium levels, and survival
      data. Normal serum sodium (NSS) was defined as serum sodium >=136 mEq/L, and low
      serum sodium (LSS) was defined as serum sodium <136 mEq/L. The impact of sodium
      levels on PFS and OS after adjusting other prognostic factors was estimated using
      Cox proportional hazard model. Results: Data were available for 257 patients
      (male/female = 182/75) with median age of 55 (21-78) years. A total of 120 (46%)
      patients had LSS whereas 137 (54%) had NSS. Patients with NSS had significantly
      longer median PFS (7 months vs. 6 months; P < 0.05) and OS (16 months vs. 11
      months; P < 0.05) compared to LSS group. Multivariate analysis showed LSS as an
      independent prognostic variable for poor survival (hazard ratio = 2.07, 95%
      confidence interval = 1.11-3.84). Conclusion: Pretreatment serum sodium level is
      an important prognostic marker in Stage IIIb/IV NSCLC patients. The simple
      possibility of testing coupled with low cost makes it an attractive biomarker.

PMID- 30197347
TI  - Effect of postoperative time for adjuvant radiotherapy in malignant phyllodes
      tumor: An institutional experience.
AB  - Introduction: Cystosarcoma phyllodes of the breast, an uncommon sarcoma found
      primarily in women of the age group of 35-55 years, constitutes <1% of all breast
      neoplasms. These tumors are resistant to chemotherapy and hormonal therapies and
      often recur aggressively after initial surgery. Limited research is available
      about the role and effectiveness of adjuvant radiotherapy in reducing
      recurrences. Objectives: Surgery has been the primary treatment modality to date
      but with high recurrence rates. The purpose of this retrospective study is to
      highlight the role of postoperative time for adjuvant radiotherapy in aggressive
      borderline and malignant phyllodes tumor (PT). Materials and Methods: This
      retrospective study reviewed 13 histopathologically proven borderline and
      malignant PT, treated with radiation therapy to the dose of 50 Gray by external
      beam radiotherapy (EBRT) after primary surgical management. Results: The mean age
      at presentation was 33 years. Right laterality was more common (60% cases).
      Although all patients presented with lump, those who had pain as an added symptom
      turned out to be histopathologically malignant later on. Histopathologically,
      66.6% patients were malignant, 20% borderline, and 13.3% benign. High mitotic
      index and stromal activity were observed in younger patients. Patients who
      received EBRT within a month of surgery had no local recurrence, whereas those
      who received EBRT after a month developed local recurrence (P = 0.012).
      Conclusion: Adjuvant radiotherapy is appropriate treatment for aggressive
      borderline and malignant PT. This study revealed that time interval between
      surgery to initiation of EBRT plays a significant role in the prevention of
      recurrence.

PMID- 30197348
TI  - Investigation of melanoma-associated antigen A4 cancer/testis antigen clinical
      relevance in esophageal squamous cell carcinoma.
AB  - Background: Esophageal squamous cell carcinoma (ESCC) is considered as the
      seventh most common cancer worldwide, and the second prevalent malignancy in the
      north of Iran. A subfamily group of tumor-specific antigens, commonly specified
      as cancer/testis antigens (CTAs), are expressed restrictedly in testis, ovary,
      and placenta. Melanoma-associated antigen A4 (MAGEA4) as a CTA is overexpressed
      in a variety of cancers. Expressional analysis of MAGEA4 protein in ESCC may be
      useful to investigate its clinical relevance leading to effective improvements in
      ESCC diagnosis and treatment. Materials and Methods: Fifty-six ESCC patients with
      no preoperative therapeutic circumstance such as radiotherapy or chemotherapy
      were analyzed to explore the protein expression level of MAGEA4 using
      immunohistochemistry assay. Results: MAGEA4 overexpression was detected in 66% of
      ESCC samples showing strong nuclear and cytoplasmic staining compared to the
      normal epithelium. There were significant correlations between MAGEA4 protein
      expression and depth of tumor invasion (P = 0.019), and the number of involved
      lymph nodes (P = 0.045). Conclusion: Because of the significant correlation of
      MAGEA4 and indices of poor prognosis, the role of this CTA may be confirmed in
      ESCC aggressiveness and metastasis. Therefore, MAGEA4 may be a promising
      therapeutic candidate for suppressing ESCC aggressiveness.

PMID- 30197349
TI  - Evaluation of boron neutron capture therapy in-phantom parameters by response
      matrix method.
AB  - Aim: Determination of boron neutron capture therapy in-phantom parameters by
      response matrix (RM) method. Materials and Methods: In this study, various in
      phantom figures-of-merit including therapeutic gain, advantage depth dose rate,
      advantage depth, therapeutic depth, treatment time, skin dose rate, and skull
      dose rate have been analyzed using the RM method. This method is based on the
      division of neutron/gamma spectrum and calculation of various dose components of
      each energy group. Summation of these dose responses is equal to the total dose
      of the whole spectrum. Based on this method, in-phantom parameters could be
      calculated by a computer program in a very short time. Results: There is a good
      agreement between direct calculation and RM method. The maximum allowable
      contaminations of the thermal and fast neutrons in a neutron beam have been
      calculated by RM method. It was found that these values are 17.4% and 2.6%, for
      thermal and fast neutron, respectively. Conclusion: The results confirm that the
      RM method is a fast method to evaluate in-phantom parameters without repeating
      simulations due to change in neutron spectrum and treatment conditions.

PMID- 30197350
TI  - Evaluation of breast lesions by digital mammography and ultrasound along with
      fine-needle aspiration cytology correlation.
AB  - Introduction: Screening and diagnostic efforts for breast cancer are critical
      because the disease has a high rate of successful outcomes with early
      identification and treatment. The mammography (MG) and Ultrasonography/
      ultrasound (USG) are individually effective diagnostic modalities for detection
      of breast pathologies. Materials and Methods: This cross-sectional, prospective,
      hospital-based study was carried out with an aim to evaluate breast lesions using
      digital MG and ultrasonography (USG) independently and in combination with fine
      needle aspiration cytology (FNAC) correlation. Results: The sensitivity,
      specificity, positive predictive value (PPV), and negative predictive value (NPV)
      of MG in detecting carcinoma breast were 77.77%, 97.72%, 87.5%, and 95.55%,
      respectively. The sensitivity, specificity, PPV, and NPV of USG in detecting
      carcinoma breast were 55.55%, 97.72%, 83.33%, and 91.48%, respectively. In our
      study population, 83.01% of breast lesions were benign, and of them, 77.27% were
      diagnosed by MG alone and 72.72% were diagnosed by USG alone. When these
      modalities were combined, 97.72% of the lesions were diagnosed. The correlation
      coefficients of MG alone (0.792), USG alone (0.631), and MG and USG combination
      (0.884) with FNAC are all positive, and P values are significant of all the
      modalities. Conclusion: This study confirms that the MG and ultrasound (USG) when
      combined have significantly higher sensitivity and NPV than observed for a single
      modality in detecting the both benign and malignant lesions of the breast.

PMID- 30197352
TI  - Gene expression analysis of noncoding PCA3 gene in patients with chronic myeloid
      leukemia.
AB  - Introduction and Objectives: Nowadays, noncoding RNAs are of special significance
      to scientists. Among RNAs, long noncoding RNAs (lncRNAs) have an important role
      in gene expression regulation. Recent studies show aberrant lncRNAs expression in
      different types of cancer including blood malignancies. As such, lncRNAs could be
      a possible way for diagnosis and treatment of certain cancers. In the current
      study, the level of PCA3 gene expression in patients with chronic myeloid
      leukemia (CML) was compared with normal individuals to find out whether the level
      of PCA3 in CML patients is increased according to our hypothesis. Materials and
      Methods: The buffy coat was collected from peripheral blood of thirty untreated
      CML patients (BCR-ABL positive) and twenty normal volunteers. RNA was extracted
      from white blood cells and cDNA was synthesized. The level of PCA3 gene
      expression was measured using quantitative reverse transcription-polymerase chain
      reaction. Results: The results showed that PCA3 has expression in both normal and
      leukemic white blood cells. The data also revealed higher expression of PCA3 in
      leukemic patients, compared to the normal counterpart (P < 0.05). Conclusion: The
      unusual increase in PCA3 gene expression in CML patients suggests the need for
      more research on mechanisms of molecular pathways related to PCA3 which could
      help achieve better treatment.

PMID- 30197351
TI  - CXCL12 rs18011157 polymorphism in patients with non-Hodgkin's lymphoma: Is it
      associated with poor outcome?
AB  - Objective: We studied CXCL12-related rs18011157 polymorphism in non-Hodgkin
      lymphoma (NHL) patients. We also determined the effect of this polymorphism on
      clinical features and outcome of NHL. Methods: We included 90 NHL patients (54
      males, 36 females) and 88 healthy controls (54 males, 34 females). CXCL12-related
      rs18011157 polymorphism was determined by polymerase chain reaction. Results:
      rs18011157 polymorphism was significantly more frequent in NHL patients with GA
      genotype than in healthy controls (37.8% vs. 20.5%, P = 0.011). The frequency of
      patients with initially high lactate dehydrogenase (LDH) level (65.8% vs. 38.5%)
      and extranodal involvement (61.1% vs. 43.8%) was significantly higher in the GA
      plus AA genotype groups when considered altogether (P = 0.01 and 0.09). Poor
      prognostic factors in univariate analysis were the presence of B symptoms,
      initially high International Prognostic Index (IPI), splenomegaly, nonresponse to
      first-line therapy, the presence of early relapse, and carrying A allele (GA plus
      AA genotypes). The independent prognostic factors in multivariate analysis were
      only early relapse and an initially high IPI score. Discussion: CXCL12 rs1801157
      polymorphism which was found to be associated with extranodal involvement and
      increased LDH in NHL might be a marker of poor prognosis in patients with GA and
      AA genotypes. Conclusions: CXCL12-related rs18011517 polymorphism was more
      frequent in NHL patients: it might be associated with NHL pathogenesis and
      outcome.

PMID- 30197353
TI  - Associations of interleukin-10 gene polymorphisms with acute myeloid leukemia in
      human (Egypt).
AB  - Background: Acute myeloid leukemia (AML) is a cytogenetically and molecularly
      heterogeneous diseases, and characterization of transforming genetic events is
      becoming increasingly important. Interleukins (ILs) are a diverse set of small
      cell signaling protein molecules. Single nucleotide polymorphisms (SNPs) of ILs
      alter their function, increasing susceptibility to different diseases. Patients
      and Methods: We investigated the association between polymorphism in IL-10 
      819T/C (rs1800871) and the risk of AML in the Egyptian population. DNA was
      isolated from bone marrow of 80 newly diagnosed adult AML patients, and 85 age-
      and sex-matched controls. Genetic analysis of IL-10 SNPs at -819T/C was assayed
      by polymerase chain reaction-restriction fragment length polymorphism. Results:
      Genetic analysis of IL-10 revealed that the Egyptians have high -819T allele
      frequencies in apparently healthy controls, whereas -819CC genotype and the -819C
      allele frequencies in the AML group were higher than in the controls (P =
      0.000086). The study suggested that subjects carrying the rs1800871CC genotype
      and C allele had a significantly increased risk for AML. Conclusion: IL-10 SNP at
      -819 was associated with enhanced AML risk, suggesting that rs1800871 provides
      clue for future studies and early detection of AML.

PMID- 30197354
TI  - A survival study of uterine cervical patients in the North East India: Hospital
      cancer registry-based analysis.
AB  - Background: Uterine cervical cancer constitutes a major proportion of cancer in
      females of our population. The objective of this study was to conduct a clinical
      study of uterine cervical cancers including their survival from hospital-cancer
      registry data. Materials and Methods: Data of uterine cervical cancer patients
      diagnosed from January 1, 2010 to December 31, 2010 and that were treated at a
      regional cancer center in North East (NE) India was recruited. The cases were
      analyzed for age group distribution, stage, and treatment types. Survival from
      the date of first diagnosis and hazard ratios (HRs) was estimated. Survival
      probability and HRs were calculated by Kaplan-Meier method and Cox-proportional
      regression analysis, respectively. Active follow-up was done for the survival
      analysis. Results: One hundred and ninety-three patients (53.4%) were included
      for the analysis. Median age was 48 years, 56.5% (108/193) of patients were in
      the age group of 45-64 years, 56.5% (109/193) were Stage II patients,
      radiotherapy alone was the main treatment modality in 65.8% (127/193) of cases, 5
      year overall survival (OS) was 40.7%, median survival was 44 months, early staged
      and advanced stage patients had 47.7%, and 29.4% 5-year OS (P = 0.002),
      respectively, and HR for advanced stages was 1.8 (P = 0.003, confidence interval
      (CI) = 1.2 to 2.7). Conclusion: Describing the clinical characteristics and
      survival of uterine cervical cancer patients is important for planning and
      identifying the gaps for its control in the NE India.

PMID- 30197355
TI  - The factors that affect the prediction of lymph node metastasis in prostate
      cancer.
AB  - Objective: We aimed to demonstrate the effects of clinical evaluations as well as
      biopsy characteristics in terms of lymph node involvement (LNI) despite the small
      number of patients in our study. Materials and Methods: A total of 221 patients
      who underwent radical prostatectomy (RP) and extended pelvic lymph node
      dissection (ePLND) in our clinic between 2010 and 2015 and who met the inclusion
      criteria were enrolled in our study group. All of the patients were evaluated in
      terms of age, prostate-specific antigen (PSA) value before transrectal ultrasound
      guided prostate biopsy (TRUSPB), digital rectal examination, Gleason score (GS)
      on TRUSPB, percentage of positive cores on TRUSPB, total number of positive
      cores, highest percentage of cancer in positive cores, and number of lymph nodes
      removed at RP. Pathological examination of the data of RP specimens, PSA values
      in follow-up after surgery, and follow-up periods was recorded. The TNM 2009
      classification was used for staging. Results: In the evaluation of LNI risk, as
      regards the assessment of predictors and outcomes with respect to the univariate
      and multivariate analyses, LNI was found in the univariate analysis to be
      associated with GS, clinical stage, number of lymph nodes removed according to
      the D'Amico risk classification. In the multivariate analysis, however, the
      number of lymph nodes removed was found significant. Conclusion: Risk
      stratification should be considered in patients with prostate cancer while
      selecting the patients who would undergo pelvic lymphadenectomy. In addition,
      ePLND should be performed to patients undergoing lymphadenectomy.

PMID- 30197356
TI  - Auditory function and quality of life in patients receiving cisplatin
      chemotherapy in head and neck cancer: A case series follow-up study.
AB  - Background: Cisplatin is one of the anticancer drugs used for head and neck
      cancers. Although some studies have shown that cisplatin can cause ototoxicity,
      periodic audiometric assessments have not been extensively studied in the Indian
      rural population. Hence, this study has been undertaken to evaluate the effects
      of cisplatin on hearing. Materials and Methods: Fifty-nine patients with squamous
      cell carcinomas of head and neck, who received cisplatin chemotherapy, were
      recruited. Serum creatinine, blood urea, serum proteins, and audiometry were
      assessed before and after the first, second, and third chemotherapy cycle. The
      cochleotoxic effect of cisplatin was assessed by pure tone audiometry. Hearing
      loss was graded accordingly. All patients were administered a quality of life
      questionnaire at baseline and at the end of the third cycle. Results: Hearing
      loss was observed in 12 patients at speech frequencies and those at higher
      frequencies were 12 (4000 Hz), 18 (6000 Hz), and 28 (8000 Hz). The hearing loss
      was symmetrical, sensorineural, and showed a strong correlation with the low
      serum albumin levels at the end of the third cycle. Dizziness was seen in eight
      patients, at the end of the study. The commonly observed adverse effects were
      nausea, vomiting, hair loss, fatigue, and tinnitus. Conclusion: The studies have
      shown hearing loss in higher frequencies, but in our study, we have observed
      hearing loss at speech frequency in 22.2% of patients receiving cisplatin, who
      also had low serum albumin levels. Periodic audiometric monitoring and serum
      albumin level may be helpful to provide timely intervention to prevent further
      hearing loss and deterioration in the quality of life.

PMID- 30197357
TI  - Combination therapy with azacitidine, etoposide, and cytarabine in the treatment
      of elderly acute myeloid leukemia patients: A single center experience.
AB  - Aims: The prognosis of acute myeloid leukemia (AML) in elderly patients is worse
      due to age and comorbidities. Lately, monotherapy with hypomethylating agents
      like azacitidine (Aza) has been used to prolong overall survival (OS) in AML
      patients. Herein, we present a retrospective study investigating treatment
      responses and OS of Aza in combination with etoposide (Eto) and cytarabine (ARA
      C) in elderly. Materials and Methods: In this study, therapies and outcomes of 37
      newly diagnosed AML patients, >60 years old, and ineligible for intensive
      chemotherapy were investigated retrospectively. Patients were grouped according
      to the treatments they received as follows - Group 1: low-dose conventional
      therapies as hydroxyurea, low-dose ARA-C, or best supportive care (n = 11); Group
      2: Aza alone (n = 6); Group 3: Aza in combination with Eto and ARA-C (Aza + Eto +
      ARA-C, n = 20). Results: It was found that an Aza + Eto + ARA-C combination
      therapy had significantly better overall response rates (P = 0.002). Combination
      group had significantly better OS than Group 1 (8 months vs. 1 month, P < 0.001),
      the difference between combination and monotherapy was not significant. The OS
      was also associated with age and performance status, but the difference was still
      statistically significant after adjustment for these factors, especially for
      patients with younger age and better performance. Conclusions: We concluded that
      combination therapy of Aza with Eto and ARA-C increases response rates, and
      prolong survival for this poor prognosed patient group. We believe that larger
      controlled studies investigating Aza combinations with other antileukemic drugs
      will contribute to the development of tolerable treatment protocols for elderly
      AML patients.

PMID- 30197358
TI  - Efficacy and safety of everolimus in hormone receptor positive breast cancer in a
      developing country: Real-life single institutional experience.
AB  - Introduction: Breast cancer is the second leading cause of cancer-related
      mortality despite the staggering improvement in cancer therapeutics. So far,
      published data illustrate endocrine therapy as the cornerstone treatment for
      patients with hormone receptor-positive metastatic breast cancer. Unfortunately,
      most patients eventually develop resistance to this treatment. Methods: The
      purpose of this study is to evaluate the efficacy of mammalian target of
      rapamycin inhibition in reversing hormone resistance in the Lebanese breast
      cancer patients. Efficacy of the intervention according to the independent
      factors and notable side effects encountered were the primary points of the
      evaluation. Results: In total, fifty patients received the combination of
      everolimus and exemestane. The mean age of the study population was 61 +/- 11
      years. Sensitivity to hormonal therapy before the start of the combination
      treatment was estimated at 64%. Response rate was 14%, and all patients were
      partial responders. After regular interval evaluation, the median progression
      free survival was 5.2 months since the initiation of therapy. The main toxicities
      associated with the combination were stomatitis (22%), myalgia (22%), skin
      toxicity (8%), and hyperglycemia (4%), all Grades 1 and 2. Conclusion: Everolimus
      has been shown to be effective in overcoming hormonal resistance in Lebanese
      breast cancer patients with results inferior to those reported in the BOLERO-2
      population. The particular differences in molecular and pathological aspects of
      breast cancer in our region should stimulate the extensive research for a better
      understanding of the particular pattern of the disease.

PMID- 30197359
TI  - Concurrent chemoradiotherapy with or without induction chemotherapy for the
      management of cervical lymph node metastasis from unknown primary tumor.
AB  - Background: To determine the impact of concurrent chemoradiotherapy (CCRT) with
      or without induction chemotherapy over radiation alone for the treatment of
      patients of cervical lymph node metastasis from an unknown primary tumor.
      Materials and Methods: A total of 96 patients with squamous cell histology of
      cervical lymph node metastases from unknown primary tumor were retrospectively
      reviewed. About 12 patients were treated with radiation alone (RT alone), 45 with
      CCRT, and 39 with induction chemotherapy followed by CCRT (ICCRT). Results:
      Overall response rate (ORR) obtained with RT alone arm was 75%, whereas for CCRT,
      it was 86.7%. About 15.4% had a complete response (CR) after induction
      chemotherapy with 92.3% ORR after the completion of CCRT. At 2 years, the disease
      free survival (DFS) was 50% in RT alone, 73% with CCRT, and 62% with ICCRT, while
      the corresponding rates at 5 years were 50% for RT alone, 45% with CCRT, and 54%
      in ICCRT arm. Conclusion: Though we obtained a high ORR with concurrent or
      induction chemotherapy arm over RT alone, there is no clear advantage in the DFS.
      The nonrandomized nature of this trial and the potential for selection bias
      should definitely be taken into account while drawing comparisons from this
      trial.

PMID- 30197360
TI  - Signal transducer and activator of transcription 3 downregulation in J774A.1 cell
      line as a model of M2 macrophages in tumor microenvironment.
AB  - Aim: Tumor-associated macrophages (TAMs) play a decisive role in the regulation
      of tumor progression by manipulating tumor oncogenesis, angiogenesis, and immune
      functions within tumor microenvironments. Tumor progression is frequently
      associated with a phenotypic switch from M1 to M2 in TAM. Activation of signal
      transducer and activator of transcription 3 (STAT3) in TAM lead to tumor-induced
      immunosuppression. STAT3 is usually constitutively activated in a variety of
      malignancies. Consequently, STAT3 has emerged as a promising target for cancer
      immunotherapy. Materials and Methods: In this study, J774A.1 cell line which is
      an M2 macrophage and overexpress STAT3 was cultured in Dulbecco's Modified Eagle
      Medium supplemented by fetal bovine serum. Then, the STAT3 silencing was
      evaluated by semi-quantitative reverse transcription-polymerase chain reaction
      (RT-PCR) using oligofectamine containing STAT3 short interfering RNA (siRNA).
      Oligofectamine containing STAT3 siRNA and control siRNA were added at a final
      concentration of 100 nM siRNA. The untransfected cells were considered as control
      group. Results: The semi-quantitative RT-PCR studies showed that J774A.1 cells
      express a high level of STAT3. Incubation of J774A.1 cells with oligofectamine
      containing STAT3 siRNA knockdown the STAT3 expression significantly both in 48
      and 72 h study; however, the effect was more pronounced in 72 h study.
      Conclusion: The expression of STAT3 in J774A.1 cells confirmed that these cells
      are M2 macrophage. Moreover, silencing of STAT3 by siRNA delivery using
      oligofectamine delivery suggests that siRNA delivery using vehicles like
      nanoliposome could be a useful therapeutic agent in M2 macrophage therapy and its
      switch to M1 macrophages. This approach could be considered as a novel
      therapeutic agent for the treatment of all cancers.

PMID- 30197361
TI  - Design of a slab phantom for breast dosimetry applications.
AB  - Background: Design of phantoms for use in radiotherapy should consider the
      complex geometry of breast tissue and inhomogeneity. The aim of this study is
      design of a slab phantom for breast dosimetry applications. Materials and
      Methods: In this study, an anatomical slab phantom was designed with cork lung
      inhomogeneity and plexi colored heart part, also describes the different size of
      breast and chest wall phantom that have been designed and constructed for
      dosimetry. Three size different phantoms have been manufactured that installed in
      one trunk, as "small," "medium," and "large," two breast size fixed and one size
      was movable on a chest wall phantom. Two different dosimeters selected to
      dosimetry in this phantom, film was chosen for this dosimetry since it provides
      good spatial resolution and suitable for two-dimensional dosimetry also measure
      dose distribution used a point dosimetry with thermoluminescent dosimeter (TLD).
      Results: The results were shown near date due to either software or phantom
      calculation. Conclusion: Application include assessment dose in the junction
      region between the tangential fields and the supraclavicular fossa field, as well
      as assess dose in inhomogeneities, the phantom were formed from a variety of
      tissue substitute materials.

PMID- 30197362
TI  - Atypical presentation of hairy cell leukemia: Significance of CD200 on flow
      cytometry.
AB  - Hairy cell leukemia (HCL) is a rare, low-grade mature B-cell neoplasm with a
      characteristic clinical, morphological, immunophenotypic, and more recently
      described molecular (BRAF p.V600E mutation) profile. It typically affects middle
      aged to elderly male who present with pancytopenia and massive splenomegaly.
      Lymphadenopathy is usually not seen. Atypical presentations such as absence of
      splenomegaly and presence of lymphadenopathy and leukocytosis, a hypoplastic
      marrow masquerading as aplastic anemia, pose a diagnostic challenge to both
      clinician and pathologist. A diligent morphological examination to look for the
      presence of hairy cells along with flow cytometric immunophenotyping showing
      consistent bright expression of CD200, in addition to well-described
      characteristic immunophenotype, helps in correctly diagnosing the case. This can
      be further confirmed by the consistent presence of V600E point mutation in BRAF
      gene. The correct identification of HCL in these unusual clinical presentations
      is of utmost importance owing to a different treatment approach in these cases.
      We present here four such cases with atypical presentation.

PMID- 30197363
TI  - Lobular breast cancer metastasis to uterus during adjuvant tamoxifen treatment: A
      case report and review of the literature.
AB  - Tamoxifen plays a critical role in the treatment of hormone receptor-positive
      breast cancer. Despite these great benefits against breast cancer, tamoxifen
      increases the risk of endometrial pathologies such as endometrial hyperplasia,
      polyp, and neoplasms because of agonistic effect on endometrial tissues.
      Therefore, gynecologic follow-up should be carried out during tamoxifen
      treatment. Uterine tumors are frequently detected as the result of presentation
      with abnormal uterine bleeding. In addition, genital tract's metastases from
      distant primary tumors can present with abnormal uterine bleeding. Therefore, it
      is important to determine whether the uterine mass is metastatic or primary
      because different treatment modalities are used for them. In this context, breast
      carcinomas are the most frequent metastatic tumors, particularly invasive lobular
      carcinoma. Here, we report an invasive lobular carcinoma case that presented with
      abnormal uterine bleeding while receiving tamoxifen therapy and has metastasize
      in the uterus.

PMID- 30197365
TI  - Poorly differentiated carcinoma of thyroid: Case report of an uncommon entity.
AB  - Malignant thyroid tumors of follicular origin comprise a spectrum, with the
      indolent well-differentiated thyroid carcinoma (WDTC) at one end and lethal
      anaplastic thyroid carcinoma (ATC) at the other. Poorly differentiated thyroid
      carcinoma (PDTC) lies intermediately between WDTC and ATC in terms of morphology
      and prognostic standpoint. This thyroglobulin producing neoplasm accounts for 4
      7% of all thyroid malignancies. PDTC has been controversial due to lack of
      defined diagnostic criteria. We hereby report a case of PDTC in a 42-year-old
      female presenting with neck swelling, pain, and dysphagia for 10 months. She was
      diagnosed as colloid goiter on fine-needle aspiration cytology. On imaging, a
      large complex thyroid with central neck nodes was seen. Total thyroidectomy and
      central neck node dissection were done. Based on the morphology, immunostaining,
      and the diagnostic criteria, a diagnosis of PDTC was made. PDTC is a diagnostic
      challenge due to its rarity and previous equivocal diagnostic criteria.

PMID- 30197364
TI  - Malignant phyllodes tumor metastatic to bilateral ovaries: A Krukenberg-like
      presentation.
AB  - Phyllodes tumor (PT) is an extremely rare tumor of the breast of mixed
      mesenchymal and epithelial origin. It may pursue a benign or malignant evolution
      with distant metastases in the latter case in 3-12% of patients. The most common
      sites of metastases are the lungs and bones. Although theoretically any organ may
      have metastasis, it is extremely rare that a PT will metastasize to the bilateral
      ovaries and present as Krukenberg tumor. Herein, we report such a case.

PMID- 30197366
TI  - Malignant peripheral nerve sheath tumor of the thorax: Unusual location of a rare
      tumor.
AB  - Malignant peripheral nerve sheath tumor (MPNST) is a rare variety as sporadic
      tumor but more common when associated with neurofibromatosis, and its usual site
      of origin lies in the extremities. MPNST of thoracic cavity is a rare site of
      origin with only anecdotal reports in literature. Progression to a large size
      without distant metastases is even rarer owing to its high metastatic potential.
      We present a case of thoracic MPNST highlighting its rarity and the treatment
      options available to provide a best possible outcome.

PMID- 30197367
TI  - Durable complete response with a short course of streptozotocin plus doxorubicin
      combination in malignant metastatic insulinoma.
AB  - Due to the cytotoxic effects of old chemotherapy regimens used in the islet cell
      tumors, capecitabine plus temozolomide combination has now become the first
      choice in the treatment of malignant insulinoma (MIoma). We present this case to
      emphasize and remind that a durable complete response in advanced stage MIoma may
      be achieved with a short course of streptozotocin plus doxorubicin combination.

PMID- 30197368
TI  - Recurrent petrositis due to nasopharyngeal carcinoma in an adult patient:
      Gradenigo's syndrome.
AB  - The early diagnosis of very rare nasopharyngeal carcinoma (NPC) is so difficult,
      to surrounded by structures such as the orbital skull base. With the invasion of
      the disease, the symptoms are manifested in different ways so that it may be
      confusion and delay in diagnosis and treatment in this situation. Including
      otological symptoms (serous otitis media), Gradenigo's syndrome is a rare
      clinical condition. The majority of published cases involve children, and the
      most common etiology is otitis media. We report a case of a diabetic man who
      presented with repeating Gradenigo's syndrome symptoms due to NPC.

PMID- 30197369
TI  - Superinfection of mature ovarian cystic teratoma in a child: An unusual
      presentation.
AB  - Mature cystic teratoma is the most common type of ovarian germ cell tumor. The
      presentation ranges from its asymptomatic nature to various complications such as
      torsion, rupture, and malignant change. The present case summarizes the rarest
      complication in the form of superinfection in a young girl without preexisting
      risk factors.

PMID- 30197370
TI  - Live birth following in vitro fertilization in a breast cancer survivor: A case
      report and review of literature.
AB  - The well-being of young cancer survivors is hampered due to the toxic effects of
      chemotherapy on the ovaries, resulting in infertility. We report a case of a 42
      year-old woman with a history of bilateral ductal carcinoma of the breast who
      underwent radical mastectomy with chemotherapy and radiotherapy was anxious to
      conceive. In vitro fertilization was performed with donor oocyte; the patient
      became pregnant and delivered a full term baby with no congenital anomalies. As
      very few have a background for providing guidance and treatment in this setting,
      this report highlights the possibility of improving the quality of reproductive
      life of young survivors by various assisted reproductive techniques, the
      importance of fertility preservation and a multidisciplinary team approach.

PMID- 30197371
TI  - Nasopharyngeal carcinoma with unusual metastasis to urinary bladder.
AB  - Nasopharyngeal carcinoma (NPC) metastasizing to urinary bladder is an uncommon
      site. We report an interesting case of NPC, on follow-up, presenting with unusual
      urinary symptoms and mimicking a primary bladder cancer. Subsequent bladder cold
      cup biopsy and immunohistochemistry unfolded a metastasis of NPC, highlighting
      unexpected and a rare presentation.

PMID- 30197372
TI  - Significance of documentation of secondhand smoke in history taking procedure of
      head and neck squamous cell carcinoma patients with no tobacco habit.

PMID- 30197373
TI  - Thalassemia, cholangiocarcinoma, and Vitamin E deficiency: A scenario in endemic
      area inSoutheast Asia.

PMID- 30197374
TI  - Retraction: Correlation of serum intercellular adhesion molecule 1 and vascular
      endothelial growth factor with tumor grading and staging in breast cancer
      patients.

PMID- 30197375
TI  - Surface-enhanced Raman Spectroscopy.

PMID- 30197376
TI  - Direct Analysis of Human Sputum for Differentiating Non-small Cell Lung Cancer by
      Neutral Desorption Extractive Electrospray Ionization Mass Spectrometry.
AB  - Human sputum, a typical highly viscous biosample, was directly characterized at
      the molecular level using neutral desorption extractive electrospray ionization
      mass spectrometry (ND-EESI-MS) without multi-step sample pretreatment, in an
      attempt to provide a method for constructing the pattern recognition of rapid
      diagnosis of lung cancer. Under the optimal experiment conditions, glucose, amino
      acids, phosphoric lipids and other typical analytes in the sputum sample could be
      used to conduct qualitative or quantitative (in arginine) analysis. More
      interestingly, the full scan mass spectra from 50 patients of non-small cell lung
      cancer, recording the mass spectral fingerprints of sputum samples, were
      differentiated from the control group (50 healthy individuals) through principal
      component analysis (PCA). These findings suggest that valuable molecular
      information concealed in human sputum could be easily revealed and applied for
      conducting qualitative or quantitative analysis by direct ND-EESI-MS analysis.

PMID- 30197377
TI  - A Simple and Rapid Fluorescent Probe for Detection of Cr3+ Based on a Coumarin
      Schiff Base in Aqueous Solution.
AB  - A new Cr3+ probe was synthesized using simple Schiff base reaction, which showed
      prominent fluorescence increasing switch before and after addition Cr3+. The
      probe proved to have excellent properties, based on both UV-vis absorption and
      fluorescence spectra. Those properties included high switching performance, good
      selectivity, and small interference with other metal ions. The fluorescent change
      mechanism of the probe was attributed to the combined action between the
      restricted C=N isomerization and the suppression of highly efficient photo
      induced electron transfer (PET) process. Moreover, this fluorescence probe for
      Cr3+ detection also has great potential for bioimaging of cancer cells.

PMID- 30197378
TI  - Quantitative Assessment of the Absolute Purity of Thiopeptcin Reference Standard
      by 1H-NMR.
AB  - Quantitative nuclear magnetic resonance (qNMR) has emerged as an easy, rapid and
      reproducible method for various pharmaceuticals. In the current study, a general
      qNMR approach for calibrating the purity of the thiopeptcin reference standard
      (also known as nocathiacin I) was developed using sulfadoxine as an internal
      standard. Experimental conditions, such as the relaxation delay time and number
      of scans, were systematically optimized, and the method was validated with
      different analytical parameters, including selectivity, stability, linearity,
      precision and robustness. To examine the reliability and feasibility of the
      present qNMR method, there was no significant difference in the quantification of
      this complex cyclic peptide compared to the mass balance method. The present
      study further exemplified that qNMR is a reliable and valuable approach for the
      assessing of absolute purity of small-molecule pharmaceuticals, which provides a
      useful tool for drug discovery and development.

PMID- 30197379
TI  - Continuous Liquid-Liquid Extraction of Uranium from Uranium-containing Wastewater
      Using an Organic Phase-refining-type Emulsion Flow Extractor.
AB  - A previously reported emulsion flow (EF) extraction system does not equip the
      refining device for any used organic phase. Therefore, the processing of large
      quantities of wastewater by using the EF extractor alone could lead to the
      accumulation of extracted components into the organic phase, and a lowering of
      the extraction performance. In the present study, we developed an organic phase
      refining-type EF system, which is equipped with a column for refining a used
      organic phase to prevent accumulation, and successfully applied it for treating
      uranium-containing wastewater.

PMID- 30197381
TI  - "Biomolecular Mass Spectrometry".

PMID- 30197382
TI  - Vanishing of ruptured adrenal mass with takotsubo cardiomyopathy.
AB  - A 45-year-old male suddenly experienced left-flank abdominal pain.
      Echocardiography revealed akinesis of the 'takotsubo cardiomyopathy' type. He
      experienced a sudden haemodynamic collapse (blood pressure, 324/154 mmHg; pulse
      rate, 180 beats/min) during emergency cardiac catheterisation. An abdominal
      computed tomography (CT) revealed expansion of a soft tissue mass 64 * 33 mm in
      dimension in the left adrenal region, with accumulation of fluid surrounding the
      left pararenal space. Three days after the attack, his urinary catecholamine
      concentrations were slightly elevated. We suspected the patient as having a
      pheochromocytoma followed by acute haemorrhagic rupture, based on signatures of
      adrenal mass, 'takotsubo cardiomyopathy', and the hypertensive crisis. Over the
      next few weeks, he recovered well as an outpatient, and his blood pressure
      remained around 110/60 mmHg without medication. Three weeks after the attack, an
      abdominal CT showed shrinkage of the ruptured adrenal mass (to a diameter of 30
      mm) and absorption of the retroperitoneal hematoma. On day 190 after the attack,
      abdominal CT did not detect any left adrenal mass. This is the first report of
      the case showing a complete vanishing of ruptured adrenal mass with takotsubo
      cardiomyopathy. Although surgical approaches for ruptured adrenal mass involve
      either emergency or elective surgery, the patients did not need even the elective
      surgery. Accumulation of the similar cases may unravel clinical factors
      predicting self-limiting of the ruptured adrenal mass to avoid unnecessary risky
      surgery.

PMID- 30197383
TI  - Micro-organic ion-associate phase extraction/micro-volume back-extraction (MVBE)
      for the pre-concentration and GF-AAS determination of cadmium, nickel and lead in
      environmental water.

PMID- 30197384
TI  - Naked-eye detection of Hg2+ in practical application using a highly selective and
      sensitive fluorescent probe.

PMID- 30197385
TI  - Colorimetric Determination of (Aminoalkyl)indole-containing Synthetic
      Cannabimimetics.

PMID- 30197386
TI  - Trace determination of cyanocobalamin (vitamin B12) by analyzing cobalt using a
      portable total reflection X-ray fluorescence spectrometer.

PMID- 30197387
TI  - Quantification of cadmium in rice by surface-enhanced Raman spectroscopy based on
      ratiometric indicator and conical holed enhancing substrates.

PMID- 30197388
TI  - [Changing concept of liver diseases in the era of hepatitis virus control].

PMID- 30197389
TI  - [Various clinical conditions after successful eradication of hepatitis C virus].

PMID- 30197390
TI  - [Hepatitis B Vaccine:the way to universal vaccination and future problems].

PMID- 30197391
TI  - [Autoimmune liver diseases -issues to be solved in Japan].

PMID- 30197392
TI  - [Renaissance of alcoholic liver disease].

PMID- 30197393
TI  - [A retrospective study of the clinical characteristics and treatment of 93 adult
      patients with eosinophilic gastroenteritis].
AB  - We performed a retrospective analysis on three patients diagnosed with EGE
      (eosinophilic gastroenteritis) at our hospital and 90 cases obtained from a case
      database. The cases' genders, ages, peripheral eosinophils, ascites, endoscopic
      findings, biopsy findings, diagnostic scores, and rates of glucocorticoid use
      were evaluated. The gender ratio was 40 males to 53 females, and the median age
      was 50. 78.5% of cases had peripheral eosinophilia. The prevalence of allergic
      diseases was 31.2%, and the incidence of ascites was 34.4%. 83.9% of endoscopic
      findings were positive, and 92.5% of biopsies were positive. The total rate of
      glucocorticoid use was 77.4%. When both score <5 and age <33 conditions were met,
      the rate of glucocorticoid use was approximately 30%, meaning it was possible to
      avoid glucocorticoid use.

PMID- 30197394
TI  - [A case of metastatic prostate cancer with gastric metastases and high serum
      CEA].
AB  - A 74-year-old male who was receiving endocrine therapy for prostate cancer, with
      multiple bone and lymph node metastases (T2bN1M1 Stage D2), underwent follow-up
      computed tomography (CT). The CT revealed multiple liver metastases, a high serum
      CEA level, and an unchanged PSA level. Upper gastrointestinal endoscopy showed an
      elevated lesion with mucosal erosion on the lesser curvature of the middle
      gastric corpus, revealed to be a metastatic prostate cancer lesion following
      immunohistochemical confirmation. This case demonstrates the potential for
      gastric metastases in patients with advanced prostate cancer and high serum CEA
      levels.

PMID- 30197395
TI  - [A case of a hepatic arterial pseudoaneurysm that occurred after acute
      cholangitis due to choledocholithiasis].
AB  - We describe a 52-year-old male who underwent endoscopic retrograde biliary
      drainage for acute cholangitis associated with common bile duct stones.
      Endoscopic papillary balloon dilatation was performed, and the stones were
      removed using a balloon catheter. Simultaneously, we initiated edoxaban for
      portal vein thrombosis. Approximately one month later, he visited our hospital
      complaining of tarry stools and dizziness. Contrast-enhanced computed tomography
      revealed a pseudoaneurysm in the hepatic artery (A7), and he was diagnosed with
      hemobilia from bile duct perforation associated with the hepatic arterial
      pseudoaneurysm. We performed an emergent transcatheter arterial embolization.
      Notably, re-bleeding has not occurred to date. Hepatic arterial pseudoaneurysms
      can occur after acute cholangitis;therefore, careful follow-up is essential.

PMID- 30197396
TI  - [A case of liver Mycobacterium avium complex syndrome, diagnosed by liver
      biopsy].
AB  - A man in his 70s was referred to our hospital for evaluation of low-grade fever,
      weight loss, and liver dysfunction. Serological tests for viral hepatitis or
      autoimmune diseases were negative. No significant findings were observed on whole
      body computed tomography (CT). Histopathologic examination of a liver biopsy
      sample revealed a non-caseating granuloma with acid-fast bacillus using the Ziehl
      Neelsen stain. Serum Mycobacterium avium complex (MAC) antibody was positive. We
      started treatment for pulmonary MAC disease. His clinical condition and liver
      function improved within two months. He was diagnosed with liver MAC disease.

PMID- 30197397
TI  - [A case of relapsed hemosuccus pancreaticus successfully treated with
      interventional radiology].
AB  - A 67-year-old male with chronic pancreatitis presented with upper abdominal pain
      and melena. Abdominal dynamic computed tomography revealed a splenic artery
      aneurysm in the main pancreatic duct. Esophagogastroduodenoscopy showed active
      bleeding from Vater's papilla. The patient was diagnosed with hemosuccus
      pancreaticus (HP) due to rupture of the aneurysm and treated with interventional
      radiology (IVR). The patient's poor lung function did not allow for a radical
      operation and a follow-up examination was recommended. The HP relapsed 7 months
      later and was successfully retreated with IVR. Although IVR is associated with a
      high recurrence rate, it is less invasive and therefore effective for treating
      relapsing HP in patients with a poor general condition.

PMID- 30197398
TI  - Delayed perforation after endoscopic submucosal dissection for mucosal colon
      cancer: A conservatively treated case.
AB  - A 66-year-old man was diagnosed from colonoscopy as having a 40-mm elevated tumor
      in the cecum. With a preoperative diagnosis of intramucosal carcinoma, endoscopic
      submucosal dissection (ESD) was performed. The tumor was resected en bloc,
      yielding a specimen with a 66-mm diameter. No perforation was detected during the
      operation.Although neither abdominal pain nor fever was observed immediately
      after ESD, abdominal pain developed on the following day. Two days after ESD, the
      abdominal pain ceased. The patient was managed conservatively with fasting and
      intravenous antibiotic treatment. Four days after ESD, abdominal X-ray revealed
      marked gas retention. Computed tomography revealed pneumoperitoneum and a pelvic
      abscess, leading to a diagnosis of delayed perforation after colonic ESD and
      paralytic intestinal obstruction. A decompression tube was then inserted
      transnasally into the small intestine. Because a gradual decrease occurred in
      intestinal gas, the decompression tube was removed. Oral ingestion was resumed 13
      days post-ESD.Delayed perforation after colonic ESD often requires emergency
      surgery. The present case was managed conservatively, despite paralytic
      intestinal obstruction. This approach is rarely employed for this condition and
      is therefore worth reporting.

PMID- 30197399
TI  - Endoscopic ultrasound-guided fine needle aspiration for pancreatic cancer.
AB  - Since the development of endoscopic ultrasound-guided fine needle aspiration (EUS
      FNA) in the early 1990s, its application has been extended to various diseases.
      For pancreatic cancer (PC), EUS-FNA can obtain specimens from the tumor itself
      with fewer complications than other methods. EUS-FNA can also be more useful for
      TNM staging than other imaging modalities. Furthermore, EUS-FNA can contribute to
      precision medicine by obtaining tissue for immunohistochemical or genetic studies
      from primary or metastatic sites of diseases. This paper will focus on the role
      of EUS-FNA in PC.

PMID- 30197400
TI  - A Novel Selective PPARalpha Modulator (SPPARMalpha), K-877 (Pemafibrate),
      Attenuates Postprandial Hypertriglyceridemia in Mice.

PMID- 30197401
TI  - How does the promoter of an oocyte-specific gene function in male germ cells?
AB  - Studying gene expression in germ cells is useful for elucidating mechanisms of
      transcriptional regulation, because different genes are activated in male and
      female germ cells. The promoter regions of an oocyte-specific gene, Oog1, have
      been characterized. Driving the expression of green fluorescent protein with
      these different promoter regions provided us with critical information on the
      regulation of gene expression. The 3.9 kb long promoter functions in both male
      and female germ cells in transgenic mice. What is the cause of this sexually
      dimorphic expression? There may be important factors within and perhaps also
      outside this 3.9 kb promoter region that are required to maintain proper sex
      specific gene expression.

PMID- 30197402
TI  - Different Neointimal Pattern in Early vs. Late In-Stent Restenosis and Clinical
      Outcomes After Drug-Coated Balloon Angioplasty - An Optical Coherence Tomography
      Study.
AB  - BACKGROUND: There are few data of clinical outcomes after drug-coated balloon
      (DCB) angioplasty according to neointimal characteristics. This study
      investigated long-term clinical outcomes according to timing of in-stent
      restenosis (ISR) and neointimal characteristics in patients with drug-eluting
      stent (DES) ISR after DCB angioplasty. Methods and Results: In all, 122 patients
      (122 ISR lesions), treated with DCB under optical coherence tomography (OCT)
      examination before and after DCB, were categorized as early ISR (<12 months; E
      ISR; n=21) and late ISR (>=12 months; L-ISR; n=101). Associations between OCT
      based neointima characteristics and period of ISR, as well as clinical outcomes
      after DCB were evaluated. Major adverse cardiac events (MACE) were a composite of
      cardiac death, non-fatal myocardial infarction, or target lesion
      revascularization (TLR). Quantitative parameters of the neointima were similar,
      but qualitative characteristics showed significant differences between the E-ISR
      and L-ISR groups. The incidence of MACE (33.3% vs. 20.8%; P=0.069) and TLR (33.3%
      vs. 18.5%; P=0.040) was higher in the E-ISR group. In addition, the incidence of
      MACE was significantly higher for heterogeneous than non-heterogeneous neointima
      (43.7% vs. 19.6%; P=0.018), but was not significantly associated with
      neoatherosclerosis (33.4% vs. 18.4%; P=0.168). CONCLUSIONS: DCB angioplasty is
      less effective for heterogeneous neointima in DES ISR. OCT-based neointimal
      evaluation may be helpful in guiding treatment of DES ISR.

PMID- 30197403
TI  - Significant Association Between Coronary Artery Low-Attenuation Plaque Volume and
      Apnea-Hypopnea Index, But Not Muscle Sympathetic Nerve Activity, in Patients With
      Obstructive Sleep Apnea Syndrome.
AB  - BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is associated with augmented
      sympathetic nerve activity and cardiovascular diseases. However, the interaction
      between coronary artery plaque characteristics and sympathetic nerve activity
      remains unclear. The purpose of this study was to clarify the relationships
      between coronary artery plaque characteristics, sleep parameters and single- and
      multi-unit muscle sympathetic nerve activity (MSNA) in OSAS patients. Methods and
      Results: A total of 32 OSAS patients who underwent full-polysomnography
      participated in this study. The coronary plaque volume was calculated with 320
      slice coronary computed tomography (CT). Single- and multi-unit MSNA were
      obtained during the daytime within 1 week from full-polysomnography. Patients
      were divided into 2 groups according to their apnea-hypopnea index (AHI) score
      (mild-moderate group, AHI <30; and severe group, AHI >=30). There were no group
      differences in risk factors for atherosclerosis; however, severe AHI patients
      showed significantly high single-unit MSNA, and low- and intermediate-attenuation
      plaque volumes. In regression analysis, the plaque volume of any CT value was not
      associated with single- or multi-unit MSNA; only AHI significantly correlated
      with low-attenuation plaque volume (R=0.52, P<0.05). CONCLUSIONS: Our findings
      provided the evidence that AHI is an independent predictor for low-attenuated,
      vulnerable plaque volume, but not daytime MSNA, in patients with OSAS.

PMID- 30197404
TI  - Effect of the Initial Strategy for Active Endocarditis Complicated With Acute
      Heart Failure.
AB  - BACKGROUND: Early surgery for infective endocarditis (IE) with acute heart
      failure (AHF) is recommended, despite clinical results being unclear. We
      investigated the effect of initial treatment in such patients. Methods and
      Results: Outcomes for 470 patients with active IE who underwent valvular surgery
      during 2009-2016 were reviewed. Of them, 177 had symptomatic AHF when diagnosed
      with IE (excluding those with cardiogenic shock or intubated for AHF). They were
      divided into 2 groups based on initial treatment: Group S (underwent valvular
      surgery immediately; n=74) and Group M (received initial medical treatment for
      infection and HF; n=103). The median (interquartile range) waiting period from
      diagnosis to surgery in Groups S and M was 1 (1-3) and 15 (8-33) days,
      respectively (P<0.001). The 5-year survival rate was higher in Group S than Group
      M (80% vs. 64%; P=0.108). Group M was divided into Group P (initial medical
      treatment was effective and elective surgery was performed; n=62) and Group E
      (emergency surgery was necessary during medical treatment; n=41); overall 5-year
      survival was significantly worse in Group E than Group P (42% vs. 79%; P<0.012).
      In Group M, multivariate analysis indicated that Staphylococcus aureus infection
      (odds ratio 3.82; 95% confidence interval 1.19-13.3; P=0.024) was a significant
      risk factor for conversion to emergency surgery. CONCLUSIONS: Considering poor
      outcomes of emergency surgery for medically refractory HF, early surgery may be a
      reasonable option for IE patients, especially those with S. aureus infection.

PMID- 30197405
TI  - Total Anomalous Pulmonary Venous Connection - Least Common Type Delineated on
      Computed Tomography.

PMID- 30197406
TI  - Synthesis of Novel Pyrazole Derivatives as Promising DNA-Binding Agents and
      Evaluation of Antitumor and Antitopoisomerases I/II Activities.
AB  - Molecules bearing pyrazole nucleus present diverse biological properties such as
      antitumor and anti-inflammatory activities that can be associated with DNA
      interactions. This study aimed to the synthesis of new pyrazol derivatives and
      evaluated their ability to interact with the DNA and antitumor and topoisomerase
      inhibition activities. All derivatives were successfully synthesized, and their
      structures were elucidated by 1H-NMR and high resolution (HR)-MS (electrospray
      ionization positive mode (ESI+)). Antiproliferative inhibition assays, UV
      titration assays, fluorescence titration assays, circular dichroism (CD) assays,
      KI quenching studies, topoisomerase inhibitory activity assays and molecular
      docking were evaluated for these compounds. Especially, compounds 5e and 5q
      showed higher antitumor activity with IC50 values <13 uM for the tested cell
      lines. However, compounds 5e and 5q did not inhibit the topoisomerase activity
      evaluated by relaxation assay. These results show that the pyrazole nucleus
      contributes to the incorporation of molecules into the DNA. Moreover, it was
      highlighted that positive charges are relevant for the design of promising
      antitumor and DNA binding compounds.

PMID- 30197408
TI  - Intramural Coronary Amyloidosis Mimicking Effort Angina Pectoris Preceding Fatal
      Heart Failure.

PMID- 30197407
TI  - An Open-Label, Single-Arm Study of a Patient-Specific Femoral Guide for Total Hip
      Arthroplasty via the Anterolateral Supine Approach, Linked with Three-Dimensional
      Surgical Support Software: Study Protocol.
AB  - In total hip arthroplasty (THA), it is generally accepted that the bones of the
      acetabular cup and femur of hip joint must be accurately cut and components
      (artificial joint parts) be implanted in exact positions at exact angles to
      achieve improvement of daily living (ADL) and quality of life (QOL). However,
      with the conventional surgical method, it is difficult to grasp and measure the
      acetabular cup and femoral stem precisely during surgery, making some kind of
      reliable guide necessary. Although it was reported that an accurate angle was
      achieved in acetabular cup implantation by support instruments for surgical
      planning, an effective support instrument is now being developed for stem
      implantation on the out-of-reach femur side. This is the first clinical study to
      assess the efficacy and safety of anterolateral approach THA using an
      extracorporeal patient-specific femoral guide (PSG) for stem implantation with
      three-dimensional (3D) surgical support software in patients with hip joint
      disease.

PMID- 30197409
TI  - Ablation Index for Catheter Ablation of Atrial Fibrillation - Clinical
      Applicability and Comparison With Force-Time Integral.
AB  - BACKGROUND: Key determinants for lesion formation in catheter ablation are
      contact force, radiofrequency (RF) power and time. The aim of this study was to
      evaluate the clinical applicability of ablation index (AI), a novel non-linear
      formula based on these components, and to compare AI with the conventional linear
      force-time interval (FTI) in pulmonary vein isolation (PVI). Methods and Results:
      Target AI ranges were defined for anatomical segments of the ipsilateral
      pulmonary veins. The operator was blinded to AI during PVI for the initial 11
      patients (group A), and was unblinded for the remaining 23 patients (group B). We
      assessed (1) the clinical value of AI to avoid excessively high and low values
      with an operator blinded vs. non-blinded to AI; and (2) the relation of AI and
      FTI in predefined ranges. In group A, 235/564 lesions (41.7%) were in the
      predefined target range as compared with 1,171/1,412 lesions (82.9%) in group B
      (P<0.001). A given AI may correspond to a wide range of FTI, as reflected by a
      quartile coefficient of dispersion for AI of 0.11 vs. a quartile coefficient of
      dispersion for FTI of 0.36. CONCLUSIONS: Incorporating RF current power, the non
      linear AI provides more comprehensive information during PVI compared with FTI.
      Given that the FTI for a given AI varies widely, the value of FTI in clinical
      practice is questionable.

PMID- 30197410
TI  - Echinacoside, an Active Constituent of Cistanche Herba, Exerts a Neuroprotective
      Effect in a Kainic Acid Rat Model by Inhibiting Inflammatory Processes and
      Activating the Akt/GSK3beta Pathway.
AB  - Echinacoside is a major compound of Cistanche Herb and has glutamate release
      inhibiting activity in the brain. Given the involvement of excitotoxicity caused
      by massive glutamate in the pathophysiology of epilepsy, we explored the
      antiepileptic effect of echinacoside on kainic acid-induced seizures in rats. The
      rats were intraperitoneally administrated echinacoside for 30 min prior to
      intraperitoneal injection with kainic acid. The results showed that kainic acid
      induced seizure-like behavioral patterns, increased glutamate concentrations,
      caused neuronal loss and microglial activation, and stimulated proinflammatory
      cytokine gene expression in the hippocampus. These kainic acid-induced
      alternations were found to be attenuated by echinacoside pretreatment.
      Furthermore, decreased Akt and glycogen synthase kinase 3beta (GSK3beta)
      phosphorylation as well as Bcl-2 expression in the hippocampus was reversed by
      the echinacoside pretreatment. These results demonstrate that echinacoside exert
      its antiepileptic and neuroprotective actions in a kainic acid rat model through
      suppressing inflammatory response and activating the Akt/GSK3beta signaling.
      Therefore, the present study suggests that echinacoside is the potentially useful
      in the prevention of epilepsy.

PMID- 30197412
TI  - A Case of Ocular Kaposi's Sarcoma Successfully Treated with Highly Active
      Antiretroviral Therapy (HAART) Combined with Docetaxel.
AB  - BACKGROUND Ocular Kaposi's sarcoma (KS) involving the conjunctiva and ocular
      adnexa is uncommon and is usually treated with cryotherapy or surgical excision.
      We report a case of ocular KS successfully treated with HAART combined with 8
      cycles of weekly docetaxel. CASE REPORT Our patient was a 24-year-old, treatment
      naive, HIV-positive (CD4 cell count 198 cells/mm3), homosexual man treated as
      having atypical hordeolum and subconjunctival hemorrhage, and later confirmed
      with pathology to have ocular KS with immunohistochemistry study showing KS with
      positive HHV8, CD34, CD31, and focal positive staining with Factor VIIIRA. HAART
      therapy was initiated combined with weekly docetaxel. With 2-month treatment of
      HAART and 8 cycles of weekly docetaxel, the KS of the bulbar conjunctiva and the
      eyelid partially resolved. CONCLUSIONS HAART combined with weekly docetaxel is an
      effective and well-tolerated option for ocular KS, which could be considered
      before cryotherapy or surgical excision.

PMID- 30197413
TI  - Polymorphism of ABCG2 Gene in Hyperuricemia Patients of Han And Uygur Ethnicity
      with Phlegm/Non-Phlegm Block in Xinjiang, China.
AB  - BACKGROUND This study investigated the relationship between hyperuricemia (with
      phlegm/non-phlegm block) and ABCG2 gene polymorphism in Han and Uygur people from
      Xinjiang, China. MATERIAL AND METHODS We recruited 600 hyperuricemia patients
      with phlegm/non-phlegm block. Genomic DNA was extracted from the whole blood.
      Gene polymorphism was classified by SnaPshot method. RESULTS The SNP loci
      rs2725220 and rs2231137 of the ABCG2 gene, but not rs2231142, were significantly
      different between patients with non-phlegm block and phlegm block (P<0.05). The
      rs2231142 allele G was the protective factor in Uygur hyperuricemia patients. In
      both Han and hyperuricemia patients, the rs2725220 allele G was a protective
      factor and the rs2231137 allele C was a risk factor. For non-phlegm-block
      hyperuricemia, the rs2231142 and rs2231137 genotypes were significantly different
      between Uygur and Han patients (P<0.05). The rs2231142 allele G was 1.563 times
      higher in the Uygur patients compared with Han, and rs2231137 allele C was 1.673
      times higher in the Uygur patients compared with the Han. For phlegm-block
      hyperuricemia, rs2231142 allele G was 1.397 times higher in the Uygur patients
      compared with the Han. CONCLUSIONS ABCG2 gene rs2231137 with more allele C tends
      to be phlegm-block type and rs2725220 with more allele G tends to be non-phlegm
      block type. In the Uygur hyperuricemia patients, ABCG2 gene rs2231142 with more
      allele G tends to be non-phlegm-block type. Allele C of rs2231137 and allele G of
      rs2231142 in ABCG2 gene are more likely to be found in the Uygur people.

PMID- 30197411
TI  - Phosphorus-mineralizing Communities Reflect Nutrient-Rich Characteristics in
      Japanese Arable Andisols.
AB  - Elucidating the soil phosphorus cycle driven by soil microbes is a vital question
      in soil microbial ecology. The Japanese arable Andisols, occupying half of the
      Japanese cropland, are known for their high phosphorus sorption capacity.
      However, limited information is currently available on microbially driven
      phosphorus mineralization in arable Andisols. We herein report that the
      phosphorus-mineralizing community in the Japanese arable Andisols showed
      characteristic distribution and composition patterns, from those in other types
      of soils. We performed a chemical analysis and microbial community analysis of 43
      arable Andisols along the Japanese archipelago. Soil phosphomonoesterase
      activities measured at pH 11 were approximately 70% of those at pH 6.5, which
      indicates that alkaline phosphatase contributes to phosphorus cycling, although
      most soil samples were acidic. Functional gene predictions based on 16S rRNA gene
      sequencing indicated that the alkaline phosphatase gene phoD was more abundant
      than other alkaline phosphatase genes and, thus, plays major roles. Hence,
      amplicon sequencing targeting phoD was performed and the results obtained showed
      that alphaproteobacterial phoD was dominant. This is in contrast to previously
      reported phoD compositions in other soils and may be attributed to the nutrient
      conditions in arable Andisols, which favor copiotrophic Alphaproteobacteria.
      Furthermore, the composition of phoD correlated with soil pH and bioavailable
      phosphorus concentrations rather than carbon or nitrogen concentrations. These
      results were partly different from previous findings, varying in the soil types
      and geographic ranges of sampling sites. Collectively, the present results
      indicate that the phosphorus-mineralizing community in the Japanese arable
      Andisols is regulated differently from those in other soil types.

PMID- 30197414
TI  - [Public health competencies and contents of Nursing degree programs in Spanish
      universities].
AB  - OBJECTIVE: The Forum of Public Health University Teachers aims to update the
      Public Health training in the degree studies. The aim was to determine the
      competences and basic contents of Public Health of Nursing Degree in Spain
      according to the criterion of the university academic staff. METHODS: Qualitative
      study, based on the nominal group technique. The snowball sampling was used to
      recruit Public Health professors of the Nursing degree, with full time dedication
      and preferably of the area of Preventive Medicine and Public Health. Finally, 17
      professors from 11 public universities participated, who formed the Forum of
      University Professors of Public Health of the Nursing Degree, which was held at
      the University of Barcelona. RESULTS: Nursing professors selected 43 of the 80
      competences which are recognized for Public Health professionals. The majority
      corresponded to the functions 'Assessing population health needs' and 'Developing
      health policies'. Professors also got to agree about 47 issues organized in 7
      blocks, with contents on introduction of Public Health, demography, health
      determinants, epidemiology of communicable and non-communicable diseases, health
      systems and health management, and health promotion and education for health.
      CONCLUSIONS: The university teachers agreed on Public Health competencies and
      contents suitable for the Nursing Degree. This consensus constitutes a reference
      to elaborate educational guides of Public Health for Nursing Degree.

PMID- 30197415
TI  - Race and precision medicine: is it time for an upgrade?

PMID- 30197416
TI  - Long-term metformin treatment in adolescents with obesity and insulin resistance,
      results of an open label extension study.
AB  - BACKGROUND/OBJECTIVES: Off-label metformin is nowadays frequently used for the
      treatment of obesity in adolescents. However, studies on long-term metformin
      treatment in adolescents with obesity are scarce. Therefore, an 18 month open
      label extension study following an 18 months randomized placebo-controlled trial
      (RCT) on the efficacy, safety, and tolerability of metformin in adolescents with
      obesity and insulin resistance was performed. SUBJECTS/METHODS: After completion
      of the RCT, metformin was offered to all participants with a body mass index
      standard deviation score (BMI-sds) > 2.3 and Homeostasis Model Assessment for
      Insulin Resistance (HOMA-IR) >= 3.4. Endpoints were change in BMI and HOMA-IR.
      RESULTS: Overall, 31/42 participants completed the extension study (74% girls,
      median age 14.8 (11.6 - 17.9), BMI 31.2 (22.3 - 45.1), HOMA-IR 3.4 (0.2 - 8.8)).
      At start, 22/42 (52.4%) participants were eligible for metformin of which 13
      (59.0%) agreed with treatment. In participants who continued metformin, an
      increase was observed in BMI (+2.2 (+0.2 to +9.0)) and HOMA-IR (+13.7 (+1.6 to
      +48.3)). In metformin naive participants, BMI stabilized after an initial
      decrease (+0.5 (-2.1 to +5.1)). For HOMA-IR, a decrease was observed (-1.1 (-4.6
      to +1.4)). CONCLUSION: While metformin treatment in metformin naive participants
      seems to result in an initial decrease in BMI and HOMA-IR, there is no evidence
      for sustained effect after prolonged use in adolescents. Limited compliance
      and/or insufficient dose may explain the differences in long-term effects between
      adolescents and adults.

PMID- 30197417
TI  - Outcomes based on prior therapy in the phase 3 METEOR trial of cabozantinib
      versus everolimus in advanced renal cell carcinoma.
AB  - BACKGROUND: In the phase 3 METEOR trial, cabozantinib improved progression-free
      survival (PFS), objective response rate (ORR), and overall survival (OS) versus
      everolimus in patients with advanced renal cell carcinoma (RCC), after prior
      antiangiogenic therapy. METHODS: Outcomes were evaluated for subgroups defined by
      prior therapy with sunitinib or pazopanib as the only prior VEGFR inhibitor, or
      prior anti-PD-1/PD-L1 therapy. RESULTS: For the prior sunitinib subgroup (N =
      267), median PFS for cabozantinib versus everolimus was 9.1 versus 3.7 months (HR
      0.43, 95% CI 0.32-0.59), ORR was 16% versus 3%, and median OS was 21.4 versus
      16.5 months (HR 0.66, 95% CI 0.47-0.93). For the prior pazopanib subgroup (N =
      171), median PFS for cabozantinib versus everolimus was 7.4 versus 5.1 months (HR
      0.67, 95% CI 0.45-0.99), ORR was 19% versus 4%, and median OS was 22.0 versus
      17.5 months (HR 0.66, 95% CI 0.42-1.04). For prior anti-PD-1/PD-L1 therapy (N =
      32), median PFS was not reached for cabozantinib versus 4.1 months for everolimus
      (HR 0.22, 95% CI 0.07-0.65), ORR was 22% versus 0%, and median OS was not reached
      versus 16.3 months (HR 0.56, 95% CI 0.21-1.52). CONCLUSIONS: Cabozantinib was
      associated with improved clinical outcomes versus everolimus in patients with
      advanced RCC, irrespective of prior therapy, including checkpoint inhibitor
      therapy.

PMID- 30197418
TI  - Low-level parental mosaicism affects the recurrence risk of holoprosencephaly.
AB  - PURPOSE: De novo variants (DNVs) represent an important fraction of the
      pathogenic variant burden in holoprosencephaly (HPE). However, unexpected
      recurrences can occur, as evidenced by multiple affected children harboring the
      same apparently DNV. This study was performed to estimate the rate of parental
      mosaicism in a cohort of patients with HPE. METHODS: We developed a targeted
      capture next-generation sequencing (NGS) panel of 153 genes with potential
      implication in HPE. Sequencing data from a cohort of 136 HPE family trios were
      analyzed to identify probands with apparently DNVs. DNVs were examined in the
      proband and their parents to detect any deviations from the expected ~50/50
      allele ratio of true heterozygosity. Selected variants were confirmed by Droplet
      DigitalTM polymerase chain reaction (ddPCR). RESULTS: We identified 28 high
      confidence DNVs, 20 of which occurred in known HPE genes. Nineteen of the 20
      variants (95%) were pathogenic or likely pathogenic. Sequence data analysis
      showed evidence of parental mosaicism in five cases, for an overall mosaicism
      rate of 26%. In addition, we found evidence for likely postzygotic events in four
      cases (50%). CONCLUSIONS: High sensitivity methods, such as high-depth NGS and
      ddPCR, are essential to providing an accurate assessment of recurrence risk in
      HPE families with apparently DNVs.

PMID- 30197419
TI  - HLBS-PopOmics: an online knowledge base to accelerate dissemination and
      implementation of research advances in population genomics to reduce the burden
      of heart, lung, blood, and sleep disorders.
AB  - Recent dramatic advances in multiomics research coupled with exponentially
      increasing volume, complexity, and interdisciplinary nature of publications are
      making it challenging for scientists to stay up-to-date on the literature.
      Strategies to address this challenge include the creation of online databases and
      warehouses to support timely and targeted dissemination of research findings.
      Although most of the early examples have been in cancer genomics and
      pharmacogenomics, the approaches used can be adapted to support investigators in
      heart, lung, blood, and sleep (HLBS) disorders research. In this article, we
      describe the creation of an HLBS population genomics (HLBS-PopOmics) knowledge
      base as an online, continuously updated, searchable database to support the
      dissemination and implementation of studies and resources that are relevant to
      clinical and public health practice. In addition to targeted searches based on
      the HLBS disease categories, cross-cutting themes reflecting the ethical, legal,
      and social implications of genomics research; systematic evidence reviews; and
      clinical practice guidelines supporting screening, detection, evaluation, and
      treatment are also emphasized in HLBS-PopOmics. Future updates of the knowledge
      base will include additional emphasis on transcriptomics, proteomics,
      metabolomics, and other omics research; explore opportunities for leveraging data
      sets designed to support scientific discovery; and incorporate advanced machine
      learning bioinformatics capabilities.

PMID- 30197420
TI  - Nitinol versus non-Nitinol prostheses in otosclerosis surgery: a meta-analysis.
AB  - The aim of this study is to perform a systematic review and meta-analysis of
      observational studies in which hearing outcomes after primary stapes surgery have
      been reported. After the surgical procedure, the effectiveness of stapes surgery
      using nickel titanium (Nitinol) or other prostheses were systematically compared
      and evaluated using a meta-analytic method. A systematic search for articles
      before January 2017 in Embase, Medline and Cochrane Library databases was
      conducted. Only articles in English were included. Inclusion criteria for
      qualitative synthesis consisted of a population of otosclerosis patients,
      intervention with primary stapes surgery using the Nitinol heat-crimping
      prosthesis compared with other type of stapes stapedotomy prostheses, and hearing
      outcome. Inclusion criteria for quantitative analysis consisted of application of
      audiometry guidelines of the American Academy of Otolaryngology Head and Neck
      Surgery Committee on Hearing and Equilibrium for evaluation of conductive hearing
      loss. A postoperative air-bone gap (ABG) <= 10 dB was considered effective. A
      bias assessment tool was developed according to Cochrane guidelines. To evaluate
      the mean age of the samples we used the chi-square test. Of the 4926 papers
      identified through the electronic database search (3695 in Pubmed/Cochrane and
      1231 in Embase), 540 studies matched the selection criteria (436 in
      Pubmed/Cochrane and 104 in Embase) after application of filters and elimination
      of duplicate articles. After analysis of the title and abstract, 459 were
      excluded (396 in Pubmed/Cochrane and 63 in Embase). Of the remaining 81 papers,
      74 were excluded according to the study selection criteria. A total of seven
      eligible studies with 1385 subjects, consisting of 637 in the Nitinol group and
      748 in the non-Nitinol group, were included in our study. There were
      statistically significant differences in the effectiveness of stapes surgery
      between the Nitinol and non-Nitinol prostheses; the data showed a combined odds
      ratio (OR) of 2.56 (95% CI 1.38-4.76, p = 0.003). There were no statistically
      significant differences in the mean pre-operative age between Nitinol and non
      Nitinol prostheses (p = 0.931). Our results suggest that the effectiveness of
      Nitinol was higher than non-Nitinol prostheses, with superiority of the number of
      patients with ABG <= 10 dB.

PMID- 30197422
TI  - Differential chemokine expression patterns in tonsillar disease.
AB  - Expression profiles of CXC- and CC-chemokines in various forms of tonsillar
      disease were studied to evaluate whether certain chemokines play a predominant
      role in a specific subset of tonsillar disease. Total RNA was isolated from 89
      biopsies (21 hyperplastic palatine tonsils, 25 adenoids, 16 chronic inflammatory
      palatine tonsils and 27 chronic inflammatory palatine tonsils with histological
      prove of acute inflammation), reverse transcribed and subjected to PCR amplifying
      IL-8, Gro-alpha, eotaxin-1, eotaxin-2, MCP-3, MCP-4 and RANTES. 2% agarose gel
      electrophoresis revealed a predominance of IL-8 in the chronic inflammatory
      palatine tonsil group compared to tonsillar hyperplasia. Furthermore, eotaxin-2
      was strongly overexpressed in adenoid samples compared to chronic inflammatory
      specimens. Our data suggest that the majority of diseases related to adenoid
      formation are mediated via an eotaxin-2 expression, whereas chronic inflammatory
      tonsillitis is associated with IL-8 upregulation. These data imply that adenoids
      are related to a Th-2, and chronic inflammatory tonsillitis to a Th-1 based
      immune response.

PMID- 30197421
TI  - New frontiers and emerging applications of 3D printing in ENT surgery: a
      systematic review of the literature.
AB  - 3D printing systems have revolutionised prototyping in the industrial field by
      lowering production time from days to hours and costs from thousands to just a
      few dollars. Today, 3D printers are no more confined to prototyping, but are
      increasingly employed in medical disciplines with fascinating results, even in
      many aspects of otorhinolaryngology. All publications on ENT surgery, sourced
      through updated electronic databases (PubMed, MEDLINE, EMBASE) and published up
      to March 2017, were examined according to PRISMA guidelines. Overall, 121 studies
      fulfilled specific inclusion criteria and were included in our systematic review.
      Studies were classified according to the specific field of application (otologic,
      rhinologic, head and neck) and area of interest (surgical and preclinical
      education, customised surgical planning, tissue engineering and implantable
      prosthesis). Technological aspects, clinical implications and limits of 3D
      printing processes are discussed focusing on current benefits and future
      perspectives.

PMID- 30197423
TI  - Effectiveness of endoscopic septoplasty in different types of nasal septal
      deformities: our experience with NOSE evaluation.
AB  - Septal deviations are the most frequent cause of nasal obstruction, and represent
      a common complaint in rhinologic practice. Since the first description of Lanza
      et al. in 1991, the use of the endoscope for the correction of septal deformities
      is increasingly more frequent. The purpose of this study is to evaluate the
      effectivenes of the endoscopic septoplasty for the correction of each of the 7
      types of septal deformities according to the Mladina's classification. A
      retrospective chart review was performed in 59 consecutive patients presenting to
      our Department for Endoscopic Septoplasty from February 2012 to August 2014. For
      each deviation, descriptive statistics (mean and standard deviation, significant
      increase/decrease) was used to asses the corrective capacity and time-dependent
      effects at follow-up. This study shows that the corrective power of endoscopic
      septoplasty is different according to the type of deviation. To our knowledge
      this is the first study that evaluates the corrective capacity of this technique
      for each deviation by analysing pre- and postoperative objective outcomes as well
      as subjective outcomes gathered from the validated NOSE questionnaire. Even if
      endoscopic septoplasty may now be considered a reliable alternative to the
      classic technique, it is essential to identify the right deformity preoperatively
      in order to provide the correct therapeutic choice.

PMID- 30197424
TI  - Extracorporeal septoplasty with internal nasal valve stabilisation.
AB  - Among various septoplasty techniques, the extracorporeal one is used for severe
      deformities of the caudal septum and consists essentially in removal of the nasal
      septum followed by correction of deformities. Reconstruction of the neo-septum is
      carried out by repositioning the septal fragments in a straight position. The
      disadvantages of this surgical technique are the septal haematoma, oedema of the
      mucosa in the valve area and some types of abnormalities of the middle third of
      the nose such as saddling of the dorsum. All of these conditions can be
      associated with various degrees of functional disorders. To prevent these
      possible complications, we developed a suture technique to fix the caudal portion
      of the neo-septum and avoid alterations or narrowing of the internal nasal valve.
      The purpose of this study is to describe extracorporeal septoplasty results with
      this suture technique in stabilising the internal nasal valve. From January 2011
      to December 2013, a retrospective review of adult patients treated with
      extracorporeal septoplasty was performed at the ENT department of Imola Hospital.
      Pre- and post-operative evaluations were carried out by rhinomanometry and
      acoustic rhinometry. Statistical analysis was performed with commercially
      available software (IBM SPSS Statistics for Windows, Version 21.0. Armonk, NY:
      IBM Corp). 133 cases fulfilled inclusion criteria and were enrolled. A
      significant improvement was evident after surgery based on the results of
      rhinomanometry and acoustic rhinology. Extracorporeal septoplasty with
      stabilisation of the internal nasal valve is an effective and reproducible
      surgical technique that yields optimal functional results.

PMID- 30197425
TI  - Olfactory evaluation in obstructive sleep apnoea patients.
AB  - The sense of smell has a high impact on the quality of life. The aim of the
      present study was to investigate olfactory dysfunction in patients with
      obstructive sleep apnoea syndrome (OSAS) and correlate the severity of disease
      with olfactory dysfunction. The relationships between nasal obstruction, nasal
      mucociliary cleareance and olfactory tests were also evaluated. Sixty patients
      with a diagnosis of OSAS were enrolled and underwent olfactory function
      evaluation. In all patients olfactory performance was tested with the Sniffin'
      Sticks method. Mucociliary transport times and anterior rhinomanometry were
      performed to identify eventual nasal obstruction and deficits in nasal
      mucociliary clearance. Olfactory dysfunction was present in 22 (36.6%) patients
      of the study group: of these, hyposmia was present in 19 (86.4%) and anosmia in 3
      (13.6%). The mean TDI score in the study group was 30. A strong correlation
      between the olfactory dysfunction and severity of sleep apnoea measured using the
      AHI was found. Patients with OSA would seem to have a high incidence of olfactory
      dysfunction. The degree of olfactory dysfunction appears to be related to the
      severity of disease. However, other co-factors such as nasal obstruction and
      reduced mucociliary clearance might also play a role in of the aetiology of this
      condition.

PMID- 30197426
TI  - Frontal brain asymmetries as effective parameters to assess the quality of
      audiovisual stimuli perception in adult and young cochlear implant users.
AB  - How is music perceived by cochlear implant (CI) users? This question arises as
      "the next step" given the impressive performance obtained by these patients in
      language perception. Furthermore, how can music perception be evaluated beyond
      self-report rating, in order to obtain measurable data? To address this question,
      estimation of the frontal electroencephalographic (EEG) alpha activity imbalance,
      acquired through a 19-channel EEG cap, appears to be a suitable instrument to
      measure the approach/withdrawal (AW index) reaction to external stimuli.
      Specifically, a greater value of AW indicates an increased propensity to stimulus
      approach, and vice versa a lower one a tendency to withdraw from the stimulus.
      Additionally, due to prelingually and postlingually deafened pathology
      acquisition, children and adults, respectively, would probably differ in music
      perception. The aim of the present study was to investigate children and adult CI
      users, in unilateral (UCI) and bilateral (BCI) implantation conditions, during
      three experimental situations of music exposure (normal, distorted and mute).
      Additionally, a study of functional connectivity patterns within cerebral
      networks was performed to investigate functioning patterns in different
      experimental populations. As a general result, congruency among patterns between
      BCI patients and control (CTRL) subjects was seen, characterised by lowest values
      for the distorted condition (vs. normal and mute conditions) in the AW index and
      in the connectivity analysis. Additionally, the normal and distorted conditions
      were significantly different in CI and CTRL adults, and in CTRL children, but not
      in CI children. These results suggest a higher capacity of discrimination and
      approach motivation towards normal music in CTRL and BCI subjects, but not for
      UCI patients. Therefore, for perception of music CTRL and BCI participants appear
      more similar than UCI subjects, as estimated by measurable and not self-reported
      parameters.

PMID- 30197427
TI  - Hearing threshold estimation by auditory steady state responses (ASSR) in
      children.
AB  - Hearing threshold identification in very young children is always problematic and
      challenging. Electrophysiological testing such as auditory brainstem responses
      (ABR) is still considered the most reliable technique for defining the hearing
      threshold. However, over recent years there has been increasing evidence to
      support the role of auditory steady-state response (ASSR). Retrospective study.
      Forty-two children, age range 3-189 months, were evaluated for a total of 83
      ears. All patients were affected by sensorineural hearing loss (thresholds >= 40
      dB HL according to a click-ABR assessment). All patients underwent ABRs, ASSR and
      pure tone audiometry (PTA), with the latter performed according to the child's
      mental and physical development. Subjects were divided into two groups: A and B.
      The latter performed all hearing investigations at the same time as they were
      older than subjects in group A, and it was then possible to achieve
      electrophysiological and PTA tests in close temporal sequence. There was no
      significant difference between the threshold levels identified at the frequencies
      tested (0.25, 0.5, 1, 2 and 4 kHz), by PTA, ABR and ASSR between the two groups
      (Mann Whitney U test, p < 0.05). Moreover, for group A, there was no significant
      difference between the ASSR and ABR thresholds when the children were very young
      and the PTA thresholds subsequently identified at a later stage. Our results show
      that ASSR can be considered an effective procedure and a reliable test,
      particularly when predicting hearing threshold in very young children at lower
      frequencies (including 0.5 kHz).

PMID- 30197428
TI  - MR imaging of endolymphatic hydrops in Meniere's disease: not all that glitters
      is gold.
AB  - Meniere's disease (MD) is a chronic condition characterised by fluctuating
      hearing loss, intermittent vertigo, tinnitus and aural fullness. Its anatomical
      and pathological counterpart is represented by endolymphatic hydrops (EH). Recent
      development and progress in magnetic resonance (MR) imaging techniques has
      enabled visualisation of EH in living human subjects using a 3 Tesla (T) scanner
      and gadolinium-based contrast-agent (GBCA) via intravenous (IV) or intra-tympanic
      (IT) administration. Data emerging from the literature about MR imaging of EH in
      MD patients are limited, and we therefore reviewed the most common MR imaging
      findings in the study of the endolymphatic space in both MD and non-MD patients.

PMID- 30197429
TI  - Anatomical and functional results of ossiculoplasty using titanium prosthesis.
AB  - Titanium ossicular chain replacement prosthesis is often used for rehabilitation
      of the columellar effect in otologic surgeries. This retrospective study aims to
      analyse the anatomical and functional results of surgeries in which a titanium
      prosthesis was used. Two hundred and eighty procedures in 256 patients operated
      on in a tertiary referral center were analysed. Aetiologies, preoperative
      audiograms, peroperative data and postoperative outcomes at 2 and 12 months
      postoperatively were reviewed. Chronic suppurative otitis media with or without
      cholesteatoma was the main aetiology (89%). There was no difference in anatomical
      results between partial and total ossicular replacement prosthesis, with an
      overall dislocation rate of 6%, and an overall extrusion rate of 3%. Regarding
      functional results, a postoperative air-bone gap <= 20 dB was achieved in 65% of
      cases, with a better result for partial compared to total ossiculoplasty (p =
      0.02). A significant difference in air bone gap closure was found when comparing
      aetiologies, with a higher air-bone gap closure in malformation cases compared to
      chronic suppurative otitis media with cholesteatoma or retraction cases (p =
      0.03). Ossiculoplasty using titanium prosthesis is a safe and effective procedure
      for rehabilitation of hearing loss, which allows reaching an air-bone gap <= 20
      dB in the majority of patients.

PMID- 30197430
TI  - Multi-option therapy vs observation for small acoustic neuroma: hearing-focused
      management.
AB  - The current treatment options for acoustic neuromas (AN) - observation,
      microsurgery and radiotherapy - should assure no additional morbidity on cranial
      nerves VII and VIII. Outcomes in terms of disease control and facial function are
      similar, while the main difference lies in hearing. From 2012 to 2016, 91 of 169
      patients (54%) met inclusion criteria for the present study, being diagnosed with
      unilateral, sporadic, intrameatal or extrameatal AN up to 1 cm in the cerebello
      pontine angle; the remaining 78 patients (46%) had larger AN and were all
      addressed to surgery. The treatment protocol for small AN included observation,
      translabyrinthine surgery, hearing preservation surgery (HPS) and radiotherapy.
      Hearing function was assessed according to the Tokyo classification and the
      American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS)
      classification. Sixty-one patients (71%) underwent observation, 19 (22%) HPS and
      6 (7%) translabyrinthine surgery; 5 patients were lost to follow-up. Median
      follow-up was 25 months. In the observation group, 24.6% of patients abandoned
      the wait-and-see policy for an active treatment; the risk of switching from
      observation to active treatment was significant for tumour growth (p = 0.0035) at
      multivariate analysis. Hearing deteriorated in 28% of cases without correlation
      with tumour growth; the rate of hearing preservation for classes C-D was higher
      than for classes A-B (p = 0.032). Patients submitted to HPS maintained an overall
      preoperative hearing class of Tokyo and AAO-HNS in 63% and 68% of cases,
      respectively. Hearing preservation rate was significantly higher for patients
      presenting with preoperative favourable conditions (in-protocol) (p = 0.046). A
      multi-option management for small AN appeared to be an effective strategy in
      terms of hearing outcomes.

PMID- 30197431
TI  - The "Italian way" to counteract obstructive sleep apnoea syndrome in children.

PMID- 30197432
TI  - Last Place? The Intersection of Ethnicity, Gender, and Race in Biomedical.

PMID- 30197434
TI  - July 2018 Quiz: Appropriate choice of an antimicrobial drug - A comment.

PMID- 30197433
TI  - The applicability of eye-controlled highlighting to the field of visual
      searching.
AB  - Objective: With the increasing amount of information presented on current human
      computer interfaces, eye-controlled highlighting has been proposed, as a new
      display technique, to optimise users' task performances. However, it is unknown
      to what extent the eye-controlled highlighting display facilitates visual search
      performance. The current study examined the facilitative effect of eye-controlled
      highlighting display technique on visual search with two major attributes of
      visual stimuli: stimulus type and the visual similarity between targets and
      distractors. Method: In Experiment 1, we used digits and Chinese words as
      materials to explore the generalisation of the facilitative effect of the eye
      controlled highlighting. In Experiment 2, we used Chinese words to examine the
      effect of target-distractor similarity on the facilitation of eye-controlled
      highlighting display. Results: The eye-controlling highlighting display improved
      visual search performance when words were used as searching target and when the
      target-distractor similarity was high. No facilitative effect was found when
      digits were used as searching target or target-distractor similarity was low.
      Conclusions: The effectiveness of the eye-controlled highlighting on a visual
      task was influenced by both stimulus type and target-distractor similarity. These
      findings provided guidelines for modern interface design with eye-based displays
      implemented.

PMID- 30197435
TI  - Reach out and get involved.

PMID- 30197436
TI  - Veterinary Medical Ethics.

PMID- 30197437
TI  - Antimicrobial resistance in bacteria isolated from horses from the Atlantic
      Provinces, Canada (1994 to 2013).
AB  - This study determined the antimicrobial susceptibility patterns and trends for
      selected bacteria isolated from horses using diagnostic data from the Atlantic
      Veterinary College Diagnostic Services Bacteriology Laboratory, Charlottetown,
      Prince Edward Island over a 20-year period. Streptococcus equi subsp.
      zooepidemicus and Escherichia coli were the most commonly isolated bacteria over
      the study period. Clinical samples were most frequently submitted from
      respiratory and reproductive systems. Most bacterial isolates were susceptible to
      ceftiofur. Resistance was most common in Gram-negative enteric bacteria, while
      streptococci were frequently susceptible to most of the antimicrobials tested
      including penicillin and trimethoprim-sulfamethoxazole. The antimicrobial
      resistance trends over the study period were relatively stable. Multi-drug
      resistance was observed in 9% of the bacterial isolates. Information provided in
      this study could be used to help guide rational, empirical antimicrobial
      treatment selection in equine practices in Atlantic Canada.

PMID- 30197438
TI  - A randomized blind placebo-controlled trial investigating the effects of
      photobiomodulation therapy (PBMT) on canine elbow osteoarthritis.
AB  - The effect of photobiomodulation therapy (PBMT) or sham light therapy on pain,
      nonsteroidal anti-inflammatory drug (NSAID) requirement, and lameness was studied
      in 20 dogs with naturally occurring elbow osteoarthritis. Dogs (n = 20) were
      randomly assigned to receive either PBMT (group PBMT; n = 11) 10 to 20 J/cm2 or a
      placebo treatment (sham light group S; n = 9) treatment 0 J/cm2, to both elbows
      for 6 weeks. Lameness score, pain score, and NSAID dose were recorded by blinded
      study personnel before and 7 to 10 days after last treatment. Reduction in NSAID
      dose occurred in 9/11 dogs in the PBMT group, and in 0/9 of group S dogs (P =
      0.0003). There was greater improvement in lameness score post PMBT versus S
      therapy (P = 0.001). A greater reduction in pain score was detected in 9/11
      parameters in group PBMT (P < 0.05). Regularly scheduled PBMT at 10 to 20 J/cm2
      per joint for 6 weeks was successful in improving lameness and pain scores, and
      in lowering NSAID requirement in canine elbow osteoarthritis patients.

PMID- 30197439
TI  - Canine visceral hemangiosarcoma treated with surgery alone or surgery and
      doxorubicin: 37 cases (2005-2014).
AB  - The purpose of this retrospective study was to determine survival times and
      prognostic factors of dogs with visceral hemangiosarcoma (HSA) treated with
      surgery alone or surgery and doxorubicin. Medical records from 2 hospitals from
      2005 to 2014 were searched for dogs with histopathologically confirmed visceral
      HSA. Data relevant to patient demographics, tumor characteristics, and outcomes
      were abstracted. The most common primary organ affected was the spleen; however,
      primary tumor location had no influence on prognosis. Twenty-three dogs were
      treated with surgery alone, while 14 dogs were treated with surgery and
      doxorubicin. There was a significant difference in survival times between dogs
      treated with surgery alone and with surgery followed by doxorubicin (66 days
      versus 274 days). Dogs with stage I tumors (196 days) had a longer median
      survival time (MST) than dogs with stage II (117 days) and stage III (23 days)
      disease. The overall MST was 179 days with a 1-year survival rate of 29.2%.

PMID- 30197440
TI  - Ultrasound measurements of the caudal vena cava before and after blood donation
      in 9 greyhound dogs.
AB  - This prospective study evaluated variation in the diameter of the caudal vena
      cava (DCdVC) as a marker of change in intravascular volume before and after blood
      donation in greyhound dogs. A preliminary study determined that the DCdVC
      increased with body weight. Nine greyhound blood donors had ultrasonographic
      images acquired of the maximum and minimum DCdVCs in transverse and sagittal
      orientations and sagittal aortic diameter (AoD) before and after blood donation.
      The collapsibility index = [(maximal mean transverse DCdVC - minimal mean
      transverse DCdVC)/maximal mean transverse DCdVC] and transverse DCdVC:AoD ratio
      were calculated for each dog. In the greyhounds, the changes in mean minimal and
      maximal transverse DCdVC (0.69 and 0.84 mm, respectively) and sagittal mean
      maximal DCdVC (0.9 mm) and collapsibility index (0.018) were significantly
      different (P < 0.05) before and after blood donation. While statistically
      significant, the magnitude of DCdVC change found in this limited number of
      greyhound dogs with 8% intravascular volume loss during blood donation was small.
      This magnitude of change is likely indistinguishable in clinical patients.

PMID- 30197441
TI  - Post-surgical outcome and prognostic factors in canine malignant melanomas of the
      haired skin: 87 cases (2003-2015).
AB  - The medical records of 87 dogs treated with surgery for cutaneous malignant
      melanoma (CMM) of the haired skin were retrospectively reviewed for overall
      survival time (OST), progression-free survival time (PFS), and prognostic
      factors. The post-surgery median PFS and median OST were 1282 days and 1363 days,
      respectively. The post-surgery metastatic rate was 21.8% with a local recurrence
      rate of 8%. Increasing mitotic index (MI) was predictive of a significantly
      decreased OST and PFS on multivariable analysis [hazard ratio (HR): 1.05, 95%
      confidence interval (CI): 1.02 to 1.07 and HR: 1.04, 95% CI: 1.02 to 1.06,
      respectively]. Increasing age was likewise predictive of a significantly
      decreased OST and PFS on multivariable analysis (HR: 1.39, 95% CI: 1.17 to 1.65
      and HR: 1.33, 95% CI: 1.14 to 1.54, respectively). These results confirm clinical
      impressions that long survival times are likely in dogs diagnosed with malignant
      melanoma of the haired skin when treated with surgery alone.

PMID- 30197442
TI  - Seminal plasma does not aid in the transport of phenolsulfonphthalein across the
      uterotubal junction in mares.
AB  - This study tested the hypothesis that the presence of prostaglandin E2 in seminal
      plasma would aid in the transport of phenolsulfonphthalein (PSP) across the
      uterotubal junction. Five mares in estrus were inseminated during estrus with PSP
      dissolved in phosphate-buffered saline and during the subsequent estrus with PSP
      added to a standard insemination dose. Serum and urine samples were obtained at
      hours 0, 1, 2, and 3 following treatment and examined for the presence of PSP.
      Phenolsulfonphthalein could not be detected in any of the urine samples collected
      from mares following either treatment. None of the serum samples collected
      following intrauterine installation of PSP in PBS contained PSP.
      Phenolsulfonphthalein was detected in serum samples from 1 mare following
      insemination with semen containing PSP. Components in seminal plasma such as PGE2
      did not facilitate the transport of PSP across the uterotubal junction as had
      been hypothesized.

PMID- 30197443
TI  - Tetralogy of Fallot with concurrent patent foramen ovale and tricuspid valve
      dysplasia in a dog.
AB  - The echocardiographic findings of a young Pomeranian-cross dog with tetralogy of
      Fallot, patent foramen ovale, and tricuspid valve dysplasia are described.
      Ongoing medical management of hypoxemia and erythrocytosis was carried out and
      the dog survived to 2 years of age. Treatment options for tetralogy of Fallot are
      discussed.

PMID- 30197444
TI  - An epidemiological study of Streptococcus suis serotypes of pigs in Ontario
      determined by a multiplex polymerase chain reaction.
AB  - The purpose of the study was to identify the serotypes of Streptococcus suis from
      tonsil swabs in clinically ill and healthy pigs in Ontario using a multiplex
      polymerase chain reaction (PCR) method. Although 22 different serotypes were
      identified, most isolates were S. suis-like bacteria or untypable.

PMID- 30197445
TI  - Changing demographics of the Canadian cow-calf industry for the period 2011 to
      2016.
AB  - From 2011 to 2016, both the number of cow-calf producers and farm operations in
      Canada decreased by 12.4%. Furthermore, the current demographics portend a
      similar or greater loss in the number of producers and farms by the next census
      (2021). This level of consolidation has implications with respect to veterinary
      education and how practitioners will service the cow-calf sector.

PMID- 30197446
TI  - Spongiform encephalomyelopathy in a calf with a congenital portosystemic shunt.
AB  - A 3-month-old Holstein heifer calf was presented because of an abnormal gait.
      Further examination revealed cranial nerve deficits, including a severely delayed
      corneal reflex. The calf was not ataxic and maintained an appetite, but was
      considerably stunted for her age. A postmortem examination resulted in a
      diagnosis of a congenital portosystemic shunt.

PMID- 30197447
TI  - Sharing in the spoils: Non-DVM wages outpacing inflation.

PMID- 30197448
TI  - An embarrassment of riches: An update on the symptomatic treatment of canine
      atopic dermatitis.

PMID- 30197449
TI  - Diagnostic Ophthalmology.

PMID- 30197450
TI  - Communication-Carbon Nanotube Fiber Microelectrodes for High Temporal
      Measurements of Dopamine.
AB  - Carbon nanotube (CNT) yarn and fiber-microelectrodes were developed for
      neurotransmitter detection using fast scan cyclic voltammetry (FSCV). Fibers were
      made by suspending CNTs in acid/surfactant and extruding into
      acetone/polyethyleneimine (PEI) and compared to a CNT yarn. They were FSCV
      frequency independent for dopamine up to 100 Hz. With faster frequencies, up to
      500 Hz, high currents are maintained, which allows a 2 ms sampling rate for FSCV,
      compared to 100 ms. CNT fibers have rough surfaces which trap dopamine and
      dopamine-o-quinone (DOQ), creating more reversible CVs. CNT yarns and fibers are
      beneficial for high sensitivity, rapid measurements of neurotransmitters.

PMID- 30197451
TI  - General Chemistry Student Attitudes and Success with Use of Online Homework:
      Traditional-Responsive versus Adaptive-Responsive.
AB  - We investigated whether use of an adaptive-responsive online homework system
      (OHS) that tailors homework to students' prior knowledge and periodically
      reassesses students to promote learning through practice retrieval has inherent
      advantages over traditional-responsive online homework. A quasi-experimental
      cohort control post-test-only design with nonequivalent groups and propensity
      scores with nearest neighbor matching (n = 6,114 pairs) was used. The adaptive
      system was found to increase the odds of a higher final letter grade for average,
      below average, and failing students. However, despite the learning advantages,
      students self-reported less favorable attitudes toward adaptive-responsive (3.15
      of 5) relative to traditional-responsive OHS (3.31). Specific to the adaptive
      OHS, the following were found: (i) student attitudes were moderately and
      positively correlated (r = 0.36, p < 0.01) to final letter grade, (ii) most
      students (95%) reported engaging in remediation of incorrect responses, (iii) a
      majority of students (69%) reported changes in study habits, and (iv) students
      recognized the benefit of using adaptive OHS by ranking its assignments and
      explanations or review materials as two of the top three most useful course
      aspects contributing to perceived learning. Instructors can use our findings to
      inform their choice of online homework system for formative assessment of
      chemistry learning by weighing the benefits, disadvantages, and learning
      pedagogies of traditional-responsive versus adaptive-responsive systems.

PMID- 30197452
TI  - Paternity Leave-Taking and Father Engagement.
AB  - Evidence suggests that paternity leave-taking is associated with higher levels of
      father involvement, but research has been limited in its focus on cross-sectional
      analyses and indicators of father involvement used. This study utilizes national
      longitudinal data to examine whether paternity leave-taking is associated with
      two indicators of father engagement when children are infants, whether paternity
      leave-taking is associated with trajectories of father engagement during the
      first few years of a child's life, and whether the relationships between
      paternity leave and father engagement are explained by fathering commitments and
      attitudes. Results suggest that longer periods of leave are associated with more
      frequent engagement in developmental tasks and caretaking when children are
      infants as well as during the first few years of children's lives. There is also
      evidence that father attitudes partially explain the relationships between length
      of paternity leave and father engagement.

PMID- 30197454
TI  - Fostering Today What is Needed Tomorrow: Investigating Students' Interest in
      Science.
AB  - This paper investigates the structure of German sixth-grade students' interest in
      science (N = 474; age 11-12 years) by considering different subject-related
      contexts (biology, chemistry, and physics) and different activities. Confirmatory
      factor analysis models were designed to validate the hypothetical structure of
      interest, connecting the whole spectrum of early school science with Holland's
      RIASEC model, and revealed that students' interest in science is best described
      by a cross-classified model with latent context and activity factors. Students
      were most interested in investigative and hands-on activities in all contexts.
      Despite the young age group, there were significant gender differences with
      regard to interest in contexts and interest in activities. For example, girls
      were more interested in artistic and realistic activities among most contexts and
      generally in the biological context. Surprisingly, boys were more interested in
      social physics activities than girls. This paper discusses implications for
      future research, for school science curricula as well as for how to engage
      students in science with particular emphasis on gender differences.

PMID- 30197453
TI  - Astrochemical evolution along star formation: Overview of the IRAM Large Program
      ASAI.
AB  - Evidence is mounting that the small bodies of our Solar System, such as comets
      and asteroids, have at least partially inherited their chemical composition from
      the first phases of the Solar System formation. It then appears that the
      molecular complexity of these small bodies is most likely related to the earliest
      stages of star formation. It is therefore important to characterize and to
      understand how the chemical evolution changes with solar-type protostellar
      evolution. We present here the Large Program "Astrochemical Surveys At IRAM"
      (ASAI). Its goal is to carry out unbiased millimeter line surveys between 80 and
      272 GHz of a sample of ten template sources, which fully cover the first stages
      of the formation process of solar-type stars, from prestellar cores to the late
      protostellar phase. In this article, we present an overview of the surveys and
      results obtained from the analysis of the 3 mm band observations. The number of
      detected main isotopic species barely varies with the evolutionary stage and is
      found to be very similar to that of massive star-forming regions. The molecular
      content in O- and C- bearing species allows us to define two chemical classes of
      envelopes, whose composition is dominated by either a) a rich content in O-rich
      complex organic molecules, associated with hot corino sources, or b) a rich
      content in hydrocarbons, typical of Warm Carbon Chain Chemistry sources. Overall,
      a high chemical richness is found to be present already in the initial phases of
      solar-type star formation.

PMID- 30197455
TI  - Ion Velocity Measurements for the Ionospheric Connections Explorer.
AB  - The Ionospheric Connections Explorer (ICON) payload includes an Ion Velocity
      Meter (IVM) to provide measurements of the ion drift motions, density,
      temperature and major ion composition at the satellite altitude near 575 km. The
      primary measurement goal for the IVM is to provide the meridional ion drift
      perpendicular to the magnetic meridian with an accuracy of 7.5 ms-1 for all
      daytime conditions encountered by the spacecraft within 15 degrees  of the
      magnetic equator. The IVM will derive this parameter utilizing two sensors, a
      retarding potential analyzer (RPA) and an ion drift meter (IDM) that have a
      robust and successful flight heritage. The IVM described here incorporates
      improvements in the design and operation to produce the most sensitive device
      that has been fielded to date. It will specify the ion drift vector, from which
      the component perpendicular to the magnetic field will be derived. In addition it
      will specify the total ion density, the ion temperature and the fractional ion
      composition. These data will be used in conjunction with measurements from the
      other ICON instruments to uncover the important connections between the dynamics
      of the neutral atmosphere and the ionosphere through the generation of dynamo
      currents perpendicular to the magnetic field and collisional forces parallel to
      the magnetic field. Here the configuration and operation of the IVM instrument
      are described as well as the procedures by which the ion drift velocity is
      determined. A description of the subsystem characteristics, which allow a
      determination of the expected uncertainties in the derived parameters, is also
      given.

PMID- 30197456
TI  - Sustained Groundwater Loss in California's Central Valley Exacerbated by Intense
      Drought Periods.
AB  - The accelerated rate of decline in groundwater levels across California's Central
      Valley results from overdrafting and low rates of natural recharge and is
      exacerbated by droughts. The lack of observations with an adequate spatiotemporal
      resolution to constrain the evolution of groundwater resources poses severe
      challenges to water management efforts. Here we present SAR interferometric
      measurements of high-resolution vertical land motion across the valley, revealing
      multiscale patterns of aquifer hydrogeological properties and groundwater storage
      change. Investigating the depletion and degradation of the aquifer-system during
      2007-2010, when the entire valley experienced a severe drought, we find that ~2%
      of total aquifer-system storage was permanently lost, owing to irreversible
      compaction of the system. Over this period, the seasonal groundwater storage
      change amplitude of 10.11 +/- 2.5 km3 modulates a long-term groundwater storage
      decline of 21.32 +/- 7.2 km3. Estimates for subbasins show more complex patterns,
      most likely associated with local hydrogeology, recharge, demand, and underground
      flow. Presented measurements of aquifer-system compaction provide a more complete
      understanding of groundwater dynamics and can potentially be used to improve
      water security.

PMID- 30197457
TI  - Process Evaluation of a Community Outpatient Program Treating Substance Use
      Disorders.
AB  - Addiction treatment can improve its impact by providing evidence-based care for
      the variety of problems that accompany substance use disorders. We conducted a
      retrospective evaluation of a new treatment program in California that aimed at
      providing multifaceted services through affiliated licensed and certified
      outpatient providers. The process evaluation used a logic model, focusing on
      program inputs, activities, and outputs, to understand the services received by
      the initial 18 clients who entered treatment. Outcomes for these patients were
      not assessed. Results indicated that clients received a variety of services: On
      average clients contracted for 118 treatment sessions and received 143 sessions.
      Among the many types of services provided, the most frequently received were
      integrative healthcare (averaging 42 sessions), group therapy (32 sessions), and
      individual therapy (32 sessions). This logic-model process evaluation indicated
      that a range of services were provided. The comprehensive approach may have
      promise for extending addiction treatment beyond its usual boundaries.

PMID- 30197458
TI  - Bayesian data analysis in the phonetic sciences: A tutorial introduction.
AB  - This tutorial analyzes voice onset time (VOT) data from Dongbei (Northeastern)
      Mandarin Chinese and North American English to demonstrate how Bayesian linear
      mixed models can be fit using the programming language Stan via the R package
      brms. Through this case study, we demonstrate some of the advantages of the
      Bayesian framework: researchers can (i) flexibly define the underlying process
      that they believe to have generated the data; (ii) obtain direct information
      regarding the uncertainty about the parameter that relates the data to the
      theoretical question being studied; and (iii) incorporate prior knowledge into
      the analysis. Getting started with Bayesian modeling can be challenging,
      especially when one is trying to model one's own (often unique) data. It is
      difficult to see how one can apply general principles described in textbooks to
      one's own specific research problem. We address this barrier to using Bayesian
      methods by providing three detailed examples, with source code to allow easy
      reproducibility. The examples presented are intended to give the reader a flavor
      of the process of model-fitting; suggestions for further study are also provided.
      All data and code are available from: https://osf.io/g4zpv.

PMID- 30197459
TI  - Cetylpyridinium chloride direct spray treatments reduce Salmonella on cantaloupe
      rough surfaces.
AB  - : Cetylpyridinium chloride (CPC) solutions (0, 0.5, or 1.0%) were applied to
      cantaloupe ("Athena" and "Hale's Best Jumbo" cultivars) rind plugs, either before
      or after inoculation with a broth culture of Salmonella Michigan (109 CFU/mL) and
      held at 37 degrees C for 1 or 24 hr. Rind plugs were diluted, shaken, and
      sonicated, and solutions were enumerated. Texture quality and color were
      evaluated over 14 days storage at 4 degrees C after 0 and 1% CPC spray
      applications. A 0.5 or 1.0% (vol/vol) application of CPC after Salmonella reduced
      the pathogen levels between 2.34 log CFU/mL and 5.16 log CFU/mL in comparison to
      the control (p < .01). No differences were observed in the firmness and color of
      1% CPC treated cantaloupes. Salmonella concentrations on cantaloupes, treated
      with 1.0% CPC, were lower after 1 hr storage as compared to 24 hr. And,
      Salmonella on "Athena" surfaces were more susceptible to CPC spray treatments
      than on "Hale's Best Jumbo." Practical applications: Cetylpyridinium chloride
      (CPC) is the active ingredient of some antiseptic oral mouth rinses, and has a
      broad antimicrobial spectrum with a rapid bactericidal effect on gram-positive
      pathogens. The spray application of CPC solutions to cantaloupe may reduce the
      level of Salmonella surface contamination during production from irrigation water
      and manure fertilizers and, during food processing by contaminated equipment and
      food handlers. Since the surfaces of cantaloupes are highly rough or irregular,
      bacteria can easily attach to these surfaces and become difficult to remove.
      Appropriate postharvest washing and sanitizing procedures are needed that can
      help control Salmonella and other pathogens on melons, especially on cantaloupes
      with nested surfaces. A direct surface spray application of CPC may be an
      alternative antimicrobial postharvest treatment to reduce pathogen contamination
      of cantaloupe melons, while providing an alternative to chlorine-based solutions.

PMID- 30197460
TI  - The instrumental resolution of a moire extensometer in light of its recent
      automatisation.
AB  - This paper assesses the instrumental resolution of a mechanical extensometer in
      light of its recent automatisation. The instrument takes advantage of the moire
      phenomenon of optical interference to measure angular rotation in two
      perpendicular planes and displacement in three dimensions. Our assessment
      systematically defines an analytical solution for the complete interpretation of
      a generic moire pattern and a set of mathematical approximations for the moire
      patterns used to measure rotation and displacement. The ultimate sensitivity of
      the automated instrument is determined on the basis of a generic least square
      differences fitting procedure while the instrumental resolution is defined on the
      basis of realistic, rather than optimal, scenarios: the resolution of the
      rotation measurements are in the order of 8.7*10-5 rad while the resolution of
      the displacement measurements are better than 5 MUm. This assessment represents
      the first step towards a global numerical repository for processed data recorded
      by the automated extensometers.

PMID- 30197461
TI  - Spatial scale, time and process in mega-events: The complexity of host community
      perspectives on neighbourhood change.
AB  - A focus on the 'mega' aspect of hallmark events can divert attention from the
      micro - those local communities who are most impacted by the event. Similarly,
      attention to the 'event' aspect underplays the long process of bidding and
      preparation before any putative legacy of urban transformation for local people.
      This paper uses qualitative data to unpack the complex and multi-layered views of
      local residents, living in a deprived neighbourhood beside the Glasgow 2014
      Commonwealth Games site in Scotland. They reflect on five years of intensive
      urban regeneration, evaluate the experience of 'lockdown' at Games time, and
      consider their hopes and fears for the future of the community. Interviewing a
      mixture of lifelong, established, new and returning residents, we found
      considerable common ground across the different groups in terms of hopes for a
      new, mixed community in the area. However, findings also highlight concerns
      around urban governance practices and the limitations of a market-led approach to
      regeneration.

PMID- 30197462
TI  - Optical Biopsy of Head and Neck Cancer Using Hyperspectral Imaging and
      Convolutional Neural Networks.
AB  - Successful outcomes of surgical cancer resection necessitate negative, cancer
      free surgical margins. Currently, tissue samples are sent to pathology for
      diagnostic confirmation. Hyperspectral imaging (HSI) is an emerging, non-contact
      optical imaging technique. A reliable optical method could serve to diagnose and
      biopsy specimens in real-time. Using convolutional neural networks (CNNs) as a
      tissue classifier, we developed a method to use HSI to perform an optical biopsy
      of ex-vivo surgical specimens, collected from 21 patients undergoing surgical
      cancer resection. Training and testing on samples from different patients, the
      CNN can distinguish squamous cell carcinoma (SCCa) from normal aerodigestive
      tract tissues with an area under the curve (AUC) of 0.82, 81% accuracy, 81%
      sensitivity, and 80% specificity. Additionally, normal oral tissues can be sub
      classified into epithelium, muscle, and glandular mucosa using a decision tree
      method, with an average AUC of 0.94, 90% accuracy, 93% sensitivity, and 89%
      specificity. After separately training on thyroid tissue, the CNN differentiates
      between thyroid carcinoma and normal thyroid with an AUC of 0.95, 92% accuracy,
      92% sensitivity, and 92% specificity. Moreover, the CNN can discriminate
      medullary thyroid carcinoma from benign multi-nodular goiter (MNG) with an AUC of
      0.93, 87% accuracy, 88% sensitivity, and 85% specificity. Classical-type
      papillary thyroid carcinoma is differentiated from benign MNG with an AUC of
      0.91, 86% accuracy, 86% sensitivity, and 86% specificity. Our preliminary results
      demonstrate that an HSI-based optical biopsy method using CNNs can provide multi
      category diagnostic information for normal head-and-neck tissue, SCCa, and
      thyroid carcinomas. More patient data are needed in order to fully investigate
      the proposed technique to establish reliability and generalizability of the work.

PMID- 30197463
TI  - Convolutional Neural Networks for the Detection of Diseased Hearts Using CT
      Images and Left Atrium Patches.
AB  - Cardiovascular disease is a leading cause of death in the United States. The
      identification of cardiac diseases on conventional three-dimensional (3D) CT can
      have many clinical applications. An automated method that can distinguish between
      healthy and diseased hearts could improve diagnostic speed and accuracy when the
      only modality available is conventional 3D CT. In this work, we proposed and
      implemented convolutional neural networks (CNNs) to identify diseased hears on CT
      images. Six patients with healthy hearts and six with previous cardiovascular
      disease events received chest CT. After the left atrium for each heart was
      segmented, 2D and 3D patches were created. A subset of the patches were then used
      to train separate convolutional neural networks using leave-one-out cross
      validation of patient pairs. The results of the two neural networks were
      compared, with 3D patches producing the higher testing accuracy. The full list of
      3D patches from the left atrium was then classified using the optimal 3D CNN
      model, and the receiver operating curves (ROCs) were produced. The final average
      area under the curve (AUC) from the ROC curves was 0.840 +/- 0.065 and the
      average accuracy was 78.9% +/- 5.9%. This demonstrates that the CNN-based method
      is capable of distinguishing healthy hearts from those with previous
      cardiovascular disease.

PMID- 30197464
TI  - Heart Chamber Segmentation from CT Using Convolutional Neural Networks.
AB  - CT is routinely used for radiotherapy planning with organs and regions of
      interest being segmented for diagnostic evaluation and parameter optimization.
      For cardiac segmentation, many methods have been proposed for left ventricular
      segmentation, but few for simultaneous segmentation of the entire heart. In this
      work, we present a convolutional neural networks (CNN)-based cardiac chamber
      segmentation method for 3D CT with 5 classes: left ventricle, right ventricle,
      left atrium, right atrium, and background. We achieved an overall accuracy of
      87.2% +/- 3.3% and an overall chamber accuracy of 85.6 +/- 6.1%. The deep
      learning based segmentation method may provide an automatic tool for cardiac
      segmentation on CT images.

PMID- 30197465
TI  - Ultrasound Segmentation of Rat Hearts Using Convolution Neural Networks.
AB  - Ultrasound is widely used for diagnosing cardiovascular diseases. However,
      estimates such as left ventricle volume currently require manual segmentation,
      which can be time consuming. In addition, cardiac ultrasound is often complicated
      by imaging artifacts such as shadowing and mirror images, making it difficult for
      simple intensity-based automated segmentation methods. In this work, we use
      convolutional neural networks (CNNs) to segment ultrasound images of rat hearts
      embedded in agar phantoms into four classes: background, myocardium, left
      ventricle cavity, and right ventricle cavity. We also explore how the inclusion
      of a single diseased heart changes the results in a small dataset. We found an
      average overall segmentation accuracy of 70.0% +/- 7.3% when combining the
      healthy and diseased data, compared to 72.4% +/- 6.6% for just the healthy
      hearts. This work suggests that including diseased hearts with healthy hearts in
      training data could improve segmentation results, while testing a diseased heart
      with a model trained on healthy hearts can produce accurate segmentation results
      for some classes but not others. More data are needed in order to improve the
      accuracy of the CNN based segmentation.

PMID- 30197466
TI  - Slow Long-Term Exhumation of the West Central Andean Plate Boundary, Chile.
AB  - We present a regional analysis of new low-temperature thermochronometer ages from
      the Central Andean fore arc to provide insights into the exhumation history of
      the western Andean margin. To derive exhumation rates over 10 million-year
      timescales, 38 new apatite and zircon (U-Th)/He ages were analyzed along six ~500
      km long near-equal-elevation, coast parallel, transects in the Coastal Cordillera
      (CC) and higher-elevation Precordillera (PC) of the northern Chilean Andes
      between latitudes 18.5 degrees S and 22.5 degrees S. These transects were
      augmented with age-elevation profiles where possible. Results are synthesized
      with previously published thermochronometric data, corroborating a previously
      observed trenchward increase in cooling ages in Peru and northern Chile. One
      dimensional thermal-kinematic modeling of all available multichronometer equal
      elevation samples reveals mean exhumation rates of <0.2 km/Myr since ~50 Ma in
      the PC and ~100 Ma in the CC. Regression of pseudovertical age-elevation
      transects in the CC yields comparable rates of ~0.05 to ~0.12 km/Myr between ~40
      and 80 Ma. Differences between the long-term mean 1-D rates and shorter-term age
      elevation-derived rates indicate low variability in the exhumation history.
      Modeling results suggest similar background exhumation rates in the CC and PC;
      younger ages in the PC are largely a function of increased heat flow and
      consequently an elevated geothermal gradient near the arc. Slow exhumation rates
      are suggestive of semiarid conditions across the region since at least the Eocene
      and deformation and development of the Andean fore arc around this time.

PMID- 30197467
TI  - Incarceration and Health.
AB  - The expansion of the penal system has been one of the most dramatic trends in
      contemporary American society. A wealth of research has examined the impact of
      incarceration on a range of later life outcomes and has considered how the penal
      system has emerged as a mechanism of stratification and inequality in the United
      States. In this article, we review the literature from a comparatively new vein
      of this research: the impact of incarceration on health outcomes. We first
      consider the impact of incarceration on a range of individual outcomes, from
      chronic health conditions to mortality. We then consider outcomes beyond the
      individual, including the health of family members and community health outcomes.
      Next, we discuss mechanisms linking incarceration and health outcomes before
      closing with a consideration of limitations in the field and directions for
      future research.

PMID- 30197468
TI  - The impact of SST-forced and unforced teleconnections on 2015/16 El Nino winter
      precipitation over the western United States.
AB  - The factors impacting western U.S. winter precipitation during the 2015/16 El
      Nino are investigated using the Modern-Era Retrospective analysis for Research
      and Applications version 2 (MERRA-2) data, and simulations with the Goddard Earth
      Observing System version 5 (GEOS-5) atmospheric general circulation model forced
      with specified sea surface temperatures (SSTs). Results reveal that the simulated
      response to the tropical Pacific SST associated with the 2015/16 El Nino was to
      produce wetter than normal conditions over much of the west coast including
      California - a result at odds with the negative precipitation anomalies observed
      over much of the Southwestern U.S. It is shown that two factors acted to partly
      counter the canonical ENSO response in that region. First, a potentially
      predictable but modest response to the unusually strong and persistent warm SST
      in the northeastern Pacific decreased precipitation in the Southwestern U.S. by
      increasing sea level pressure, driving anticyclonic circulation and atmospheric
      descent, and reducing moisture transport into that region. Second, large-scale
      unforced (by SST) components of atmospheric variability (consisting of the
      leading modes of unpredictable intra-ensemble variability) resembling the
      positive phase of the North Atlantic Oscillation and Arctic Oscillation are found
      to be an important contributor to the drying over the western U.S. While a
      statistical reconstruction of the precipitation from our simulations that account
      for internal atmospheric variability does much to close the gap between the
      ensemble mean and observed precipitation in the Southwestern U.S., some
      differences remain, indicating that model error is also playing a role.

PMID- 30197469
TI  - Soft Nondamaging Contacts Formed from Eutectic Ga-In for the Accurate
      Determination of Dielectric Constants of Organic Materials.
AB  - A method for accurately measuring the relative dielectric constant (epsilonr) of
      thin films of soft, organic materials is described. The effects of the
      bombardment of these materials with hot Al atoms, the most commonly used top
      electrode, are mitigated by using electrodes fabricated from eutectic gallium
      indium (EGaIn). The geometry of the electrode is defined by injection into
      microchannels to form stable structures that are nondamaging and that conform to
      the topology of the organic thin film. The epsilonr of a series of references and
      new organic materials, polymers, and fullerene derivatives was derived from
      impedance spectroscopy measurements for both Al and EGaIn electrodes showing the
      specific limitations of Al with soft, organic materials and overcoming them with
      EGaIn to determine their dielectric properties and provide realistic values of
      epsilonr.

PMID- 30197471
TI  - Early fire detection for underground diesel fuel storage areas.
AB  - With the increased use of mobile diesel-powered equipment in underground mines,
      the fire risk posed by underground diesel fuel storage areas is a concern. To
      reduce the risk associated with the storage and transfer of large quantities of
      diesel fuel in permanent underground mine storage areas, an experimental study
      was conducted to investigate the responses of different sensors for early
      detection of diesel fuel fires in a storage area. Fire sensors tested in this
      study were four carbon monoxide (CO) sensors, two smoke sensors, and one flame
      sensor. A series of fire tests were conducted in the NIOSH Safety Research Coal
      Mine, Bruceton, PA, using various fire sizes at different ventilation airflow
      velocities and fire locations. Response times for different sensors were
      analyzed, and the results suggest that the flame sensor and smoke sensors
      resulted in shorter response times in most tests compared to the CO sensors.
      Based on the test results, the appropriate sensor locations for early fire
      detection in a diesel fuel storage area were identified. The results of this
      study can help mining companies to select appropriate fire sensors for
      underground diesel fuel storage areas and improve the deployment of these sensors
      to ensure the safety of underground miners.

PMID- 30197470
TI  - Unveiling the Outstanding Oxygen Mass Transport Properties of Mn-Rich Perovskites
      in Grain Boundary-Dominated La0.8Sr0.2(Mn1-x Co x )0.85O3+/-delta Nanostructures.
AB  - Ion transport in solid-state devices is of great interest for current and future
      energy and information technologies. A superior enhancement of several orders of
      magnitude of the oxygen diffusivity has been recently reported for grain
      boundaries in lanthanum-strontium manganites. However, the significance and
      extent of this unique phenomenon are not yet established. Here, we fabricate a
      thin film continuous composition map of the La0.8Sr0.2(Mn1-x Co x )0.85O3+/-delta
      family revealing a substantial enhancement of the grain boundary oxygen mass
      transport properties for the entire range of compositions. Through isotope
      exchange depth profiling coupled with secondary ion mass spectroscopy, we show
      that this excellent performance is not directly linked to the bulk of the
      material but to the intrinsic nature of the grain boundary. In particular, the
      great increase of the oxygen diffusion in Mn-rich compositions unveils an
      unprecedented catalytic performance in the field of mixed ionic-electronic
      conductors. These results present grain boundaries engineering as a novel
      strategy for designing highly performing materials for solid-state ionics-based
      devices.

PMID- 30197472
TI  - Collective Motion in Human Crowds.
AB  - The balletic motion of bird flocks, fish schools, and human crowds is believed to
      emerge from local interactions between individuals, in a process of self
      organization. The key to explaining such collective behavior thus lies in
      understanding these local interactions. After decades of theoretical modeling,
      experiments using virtual crowds and analysis of real crowd data are enabling us
      to decipher the 'rules' governing these interactions. Based on such results, we
      build a dynamical model of how a pedestrian aligns their motion with that of a
      neighbor, and how these binary interactions are combined within a neighborhood in
      a crowd. Computer simulations of the model generate coherent motion at the global
      level and reproduce individual trajectories at the local level. This approach
      yields the first experiment-driven, bottom-up model of collective motion,
      providing a basis for understanding more complex patterns of crowd behavior in
      both everyday and emergency situations.

PMID- 30197473
TI  - Assessment of magnification of digital radiographs in total HIP arthroplasty.
AB  - Objective: Total hip arthroplasty (THA) preoperative planning requires the
      calibration of X-ray. We evaluate the magnification in standard pelvis hip X-ray
      and determine its relation with biometric factors. Methods: The magnification of
      140 THA X-ray were calculated with the known femoral head (MFFH) and acetabular
      component (MFAC). Gender, age, height, weight, and BMI were correlated to the
      magnification. Results: The MFFH and MFAC were 113.2 +/- 4,4 and 113,4 +/- 3,6
      respectively. No significant differences by gender and no correlation with
      height, weight or BMI. Conclusion: The X-ray magnification should be calibrated
      in every institution to improve the accuracy of preoperative planning.

PMID- 30197474
TI  - Time to think: Selecting patients who may benefit from synchronous resection of
      primary pancreatic cancer and liver metastases.
AB  - Pancreatic cancer remains a lethal disease and is associated with poor prognosis,
      particularly for patients with distant metastasis at diagnosis. Recently, Oweira
      reported a retrospective study that included 13233 metastatic pancreatic cancer
      patients from the Surveillance, Epidemiology and End Results database. They
      demonstrated that pancreatic cancer patients with isolated liver metastases had
      worse outcomes than patients with isolated lung metastases or distant nodal
      metastases. At present, the standard treatment for metastatic pancreatic cancer
      is chemotherapy. However, improvement in the safety of pancreatic surgery has led
      to the consideration of more aggressive surgical approaches. Schneitler reported
      two cases of hepatic metastatic pancreatic cancer in which negative margin (R0)
      resection and long survival were achieved after effective preoperative
      chemotherapy. In general, these two studies indicate that although pancreatic
      cancer patients with liver metastasis have a poor prognosis, surgical approaches
      may prolong survival for a few of these patients. A strategy to select hepatic
      metastatic pancreatic cancer patients who may benefit from surgical intervention
      is urgently needed.

PMID- 30197475
TI  - From bench to bedside: Fecal calprotectin in inflammatory bowel diseases clinical
      setting.
AB  - Fecal calprotectin (FC) has emerged as one of the most useful tools for clinical
      management of inflammatory bowel diseases (IBD). Many different methods of
      assessment have been developed and different cut-offs have been suggested for
      different clinical settings. We carried out a comprehensive literature review of
      the most relevant FC-related topics: the role of FC in discriminating between IBD
      and irritable bowel syndrome (IBS) and its use in managing IBD patients In
      patients with intestinal symptoms, due to the high negative predictive value a
      normal FC level reliably rules out active IBD. In IBD patients a correlation with
      both mucosal healing and histology was found, and there is increasing evidence
      that FC assessment can be helpful in monitoring disease activity and response to
      therapy as well as in predicting relapse, post-operative recurrence or pouchitis.
      Recently, its use in the context of a treat-to-target approach led to a better
      outcome than clinically-based therapy adjustment in patients with early Crohn's
      disease. In conclusion, FC measurement represents a cheap, safe and reliable
      test, easy to perform and with a good reproducibility. The main concerns are
      still related to the choice of the optimal cut-off, both for differentiating IBD
      from IBS, and for the management of IBD patients.

PMID- 30197476
TI  - Updates on the hepatocyte growth factor/c-Met axis in hepatocellular carcinoma
      and its therapeutic implications.
AB  - Hepatocellular carcinoma (HCC) is the fifth most common cancer and is the second
      leading cause of cancer death. Since the diagnosis of HCC is difficult, in many
      cases patients with HCC are diagnosed advanced stage of development. Hepatocyte
      growth factor (HGF)/c-mesenchymal-epithelial transition receptor (c-Met) axis is
      a key signaling pathway in HCC, either via canonical or non-canonical pathways.
      Available treatments against HCC based upon HGF/c-Met inhibition can increase
      patient lifespan, but do not reach the expected therapeutic benefits. In HCC, c
      Met monomers can bind other receptor monomers, activating several noncanonical
      signaling pathways, leading to increased cell proliferation, invasion, motility,
      and drug resistance. All of these processes are enhanced by the tumor
      microenvironment, with stromal cells contributing to boost tumor progression
      through oxidative stress, angiogenesis, lymphangiogenesis, inflammation, and
      fibrosis. Novel treatments against HCC are being explored to modulate other
      targets such as microRNAs, methyltransferases, and acetyltransferases, which are
      all involved in the regulation of gene expression in cancer. This review compiles
      basic knowledge regarding signaling pathways in HCC, and compounds already used
      or showing potential to be used in clinical trials.

PMID- 30197477
TI  - p21-activated kinase signalling in pancreatic cancer: New insights into tumour
      biology and immune modulation.
AB  - Pancreatic cancer is one of the most aggressive and lethal malignancies
      worldwide, with a very poor prognosis and a five-year survival rate less than 8%.
      This dismal outcome is largely due to delayed diagnosis, early distant
      dissemination and resistance to conventional chemo-therapies. Kras mutation is a
      well-defined hallmark of pancreatic cancer, with over 95% of cases harbouring
      Kras mutations that give rise to constitutively active forms of Kras. As
      important down-stream effectors of Kras, p21-activated kinases (PAKs) are
      involved in regulating cell proliferation, apoptosis, invasion/migration and
      chemo-resistance. Immunotherapy is now emerging as a promising treatment modality
      in the era of personalized anti-cancer therapeutics. In this review, basic
      knowledge of PAK structure and regulation is briefly summarised and the pivotal
      role of PAKs in Kras-driven pancreatic cancer is highlighted in terms of tumour
      biology and chemo-resistance. Finally, the involvement of PAKs in immune
      modulation in the tumour microenvironment is discussed and the potential
      advantages of targeting PAKs are explored.

PMID- 30197480
TI  - Establishment, functional and genetic characterization of a colon derived large
      cell neuroendocrine carcinoma cell line.
AB  - AIM: To establish cell line and patient-derived xenograft (PDX) models for
      neuroendocrine carcinomas (NEC) which is highly desirable for gaining insight
      into tumor development as well as preclinical research including biomarker
      testing and drug response prediction. METHODS: Cell line establishment was
      conducted from direct in vitro culturing of colonic NEC tissue (HROC57). A PDX
      could also successfully be established from vitally frozen tumor samples.
      Morphological features, invasive and migratory behavior of the HROC57 cells as
      well as expression of neuroendocrine markers were vastly analyzed. Phenotypic
      analysis was done by microscopy and multicolor flow cytometry. The extensive
      molecular-pathological profiling included mutation analysis, assessment of
      chromosomal and microsatellite instability; and in addition, fingerprinting
      (i.e., STR analysis) was performed from the cell line in direct comparison to
      primary patient-derived tissues and the PDX model established. Drug
      responsiveness was examined for a panel of chemotherapeutics in clinical use for
      the treatment of solid cancers. RESULTS: The established cell line HROC57 showed
      distinct morphological and molecular features of a poorly differentiated large
      cell NEC with KI-67 > 50%. Molecular-pathological analysis revealed a CpG island
      promoter methylation positive cell line with microsatellite instability being
      absent. The following mutation profile was observed: KRAS (wt), BRAF (mut). A
      high sensitivity to etoposide, cisplatin and 5-FU could be demonstrated while it
      was more resistant towards rapamycin. CONCLUSION: We successfully established and
      characterized a novel patient-derived NEC cell line in parallel to a PDX model as
      a useful tool for further analysis of the biological characteristics and for
      development of novel diagnostic and therapeutic options for NEC.

PMID- 30197479
TI  - Antiangiogenic therapy for portal hypertension in liver cirrhosis: Current
      progress and perspectives.
AB  - Developing medicines for hemodynamic disorders that are characteristic of
      cirrhosis of the liver is a relevant problem in modern hepatology. The increase
      in hepatic vascular resistance to portal blood flow and subsequent hyperdynamic
      circulation underlie portal hypertension (PH) and promote its progression,
      despite the formation of portosystemic collaterals. Angiogenesis and vascular bed
      restructurization play an important role in PH pathogenesis as well. In this
      regard, strategic directions in the therapy for PH in cirrhosis include
      selectively decreasing hepatic vascular resistance while preserving or increasing
      portal blood flow, and correcting hyperdynamic circulation and pathological
      angiogenesis. The aim of this review is to describe the mechanisms of
      angiogenesis in PH and the methods of antiangiogenic therapy. The PubMed
      database, the Google Scholar retrieval system, and the reference lists from
      related articles were used to search for relevant publications. Articles
      corresponding to the aim of the review were selected for 2000-2017 using the
      keywords: "liver cirrhosis", "portal hypertension", "pathogenesis",
      "angiogenesis", and "antiangiogenic therapy". Antiangiogenic therapy for PH was
      the inclusion criterion. In this review, we have described angiogenesis
      inhibitors and their mechanism of action in relation to PH. Although most of them
      were studied only in animal experiments, this selective therapy for abnormally
      growing newly formed vessels is pathogenetically reasonable to treat PH and
      associated complications.

PMID- 30197478
TI  - Long non-coding RNAs involved in metastasis of gastric cancer.
AB  - Gastric cancer (GC) is one of the most frequently diagnosed malignant diseases.
      The molecular mechanisms of metastasis remain unclear. Recently, studies have
      shown that long non-coding RNAs (lncRNAs) play critical roles in metastasis.
      Therefore, deeper understanding of this mechanism could provide potential
      diagnostic tools and therapeutic targets for metastatic GC. This review focuses
      on dysregulated lncRNAs in GC metastases. Due to the identification of multiple
      diverse mechanisms involved in GC metastasis, we classified them into seven
      categories, including lncRNAs related to epithelial-mesenchymal transition,
      regulation of degradation of extracellular matrix, angiopoiesis, vasculogenic
      mimicry, and immunologic escape. As the TNM stage is pivotal for evaluating the
      severity and prognosis of GC patients, we summarize the lncRNAs relevant to
      lymphatic metastasis, distant metastasis and TNM classification. This review
      summarizes the lncRNAs related to metastasis, which may provide insight into the
      mechanisms, and provide potential markers for prognostic prediction and
      monitoring the relapse of GC.

PMID- 30197481
TI  - Metabolomic alterations and chromosomal instability status in gastric cancer.
AB  - AIM: To explore the correlation of metabolomics profiles of gastric cancer (GC)
      with its chromosomal instability (CIN) status. METHODS: Nineteen GC patients were
      classified as CIN and non-CIN type by The Cancer Genome Atlas Research Group
      system, based on 409 oncogenes and tumor suppressor genes sequenced. The aqueous
      metabolites of the GC tumor and its surrounding adjacent healthy tissues were
      identified through liquid chromatography-mass spectrometry. Groups were compared
      by defining variable importance in projection score of > 1.2, a fold change value
      or its reciprocal of > 1.2, and a P value of < 0.05 as a significant difference.
      RESULTS: In total, twelve men and seven women were enrolled, with a median age of
      66 years (range, 47-87 years). The numbers of gene alterations in the CIN GC
      group were significantly higher than those in the non-CIN GC (32-218 vs 2-17; P <
      0.0005). Compared with the adjacent healthy tissues, GC tumors demonstrated
      significantly higher aspartic acid, citicoline, glutamic acid, oxidized
      glutathione, succinyladenosine, and uridine diphosphate-N-acetylglucosamine
      levels, but significantly lower butyrylcarnitine, glutathione
      hydroxyhexanoycarnitine, inosinic acid, isovalerylcarnitine, and threonine levels
      (all P < 0.05). CIN tumors contained significantly higher phosphocholine and
      uridine 5'-monophosphate levels but significantly lower beta-citryl-L-glutamic
      acid levels than did non-CIN tumors (all P < 0.05). CIN GC tumors demonstrated
      additional altered pathways involving alanine, aspartate, and glutamate
      metabolism, glyoxylate and dicarboxylate metabolism, histidine metabolism, and
      phenylalanine, tyrosine, and tryptophan biosynthesis. CONCLUSION: Metabolomic
      profiles of GC tumors and the adjacent healthy tissue are distinct, and the CIN
      status is associated with downstream metabolic alterations in GC.

PMID- 30197482
TI  - Beta-blockers and physical frailty in patients with end-stage liver disease.
AB  - AIM: To investigate beta-blocker (BB) use in patients with cirrhosis and
      determine their effects on physical frailty and overall survival. METHODS: Adult
      outpatients with cirrhosis listed for liver transplantation underwent testing of
      physical frailty using the performance-based Liver Frailty Index, comprised of
      chair stands, grip strength, and balance testing, as well as self-reported
      assessments of exhaustion and physical activity. BB use was assessed from medical
      chart review. Univariable and multivariable logistic regression were performed to
      determine BB use and their association with measures of physical frailty.
      Competing risk analyses were performed to determine the effect of BB use on wait
      list mortality, as defined by death or delisting for being too sick for
      transplant. RESULTS: Of 344 patients, 35% were female, median age was 60, median
      model for end stage liver disease was 15, and 53% were prescribed a BB. Compared
      to those not on BB, patients on BB were similar except for percentage female (25%
      vs 46%; P < 0.001) and BMI (29 vs 28; P = 0.008). With respect to tests of
      physical frailty, BB use was not associated with increased odds of frailty (by
      the Liver Frailty Index), exhaustion, or low physical activity. BB use was,
      however, significantly associated with a decreased adjusted risk of mortality
      (SHR 0.55; P = 0.005). CONCLUSION: In patients with cirrhosis awaiting liver
      transplantation, BB use is not associated with physical frailty. We confirmed the
      known survival benefits with BB use, and concerns about adverse effects should
      not deter their utilization when indicated.

PMID- 30197483
TI  - Secondary endoscopic submucosal dissection for locally recurrent or incompletely
      resected gastric neoplasms.
AB  - AIM: To investigate the feasibility and safety of secondary endoscopic submucosal
      dissection (ESD) for residual or locally recurrent gastric tumors. METHODS:
      Between 2010 and 2017, 1623 consecutive patients underwent ESD for gastric
      neoplasms at a single tertiary referral center. Among these, 28 patients
      underwent secondary ESD for a residual or locally recurrent tumor. Our analysis
      compared clinicopathologic factors between primary ESD and secondary ESD groups.
      RESULTS: The en bloc resection and curative rate of resection of secondary ESD
      were 92.9% and 89.3%, respectively. The average procedure time of secondary ESD
      was significantly longer than primary ESD (78.2 min vs 55.1 min, P = 0.004), and
      the adverse events rate was not significantly different but trended slightly
      higher in the secondary ESD group compared to the primary ESD group (10.7% vs
      3.8%, P = 0.095). Patients who received secondary ESD had favorable outcomes
      without severe adverse events. During a mean follow-up period, no local
      recurrence occurred in patients who received secondary ESD. CONCLUSION: Secondary
      ESD of residual or locally recurrent gastric tumors appears to be a feasible and
      curative treatment though it requires greater technical efficiency and longer
      procedure time.

PMID- 30197485
TI  - Percutaneous transhepatic extraction and balloon dilation for simultaneous
      gallbladder stones and common bile duct stones: A novel technique.
AB  - AIM: To evaluate the clinical efficacy and safety of an innovative percutaneous
      transhepatic extraction and balloon dilation (PTEBD) technique for clearance of
      gallbladder stones in patients with concomitant stones in the common bile duct
      (CBD). METHODS: The data from 17 consecutive patients who underwent PTEBD for
      clearance of gallbladder stones were retrospectively analyzed. After removal of
      the CBD stones by percutaneous transhepatic balloon dilation (PTBD), the
      gallbladder stones were extracted to the CBD and pushed into the duodenum with a
      balloon after dilation of the sphincter of Oddi. Large stones were fragmented
      using a metallic basket. The patients were monitored for immediate adverse events
      including hemorrhage, perforation, pancreatitis, and cholangitis. During the two
      year follow-up, they were monitored for stone recurrence, reflux cholangitis, and
      other long-term adverse events. RESULTS: Gallbladder stones were successfully
      removed in 16 (94.1%) patients. PTEBD was repeated in one patient. The mean
      hospitalization duration was 15.9 +/- 2.2 d. Biliary duct infection and
      hemorrhage occurred in one (5.9%) patient. No severe adverse events, including
      pancreatitis or perforation of the gastrointestinal or biliary tract occurred.
      Neither gallbladder stone recurrence nor refluxing cholangitis had occurred two
      years after the procedure. CONCLUSION: Sequential PTBD and PTEBD are safe and
      effective for patients with simultaneous gallbladder and CBD stones. These
      techniques provide a new therapeutic approach for certain subgroups of patients
      in whom endoscopic retrograde cholangiopancreatography/endoscopic sphincterotomy
      or surgery is not appropriate.

PMID- 30197484
TI  - Differentiation of intrahepatic cholangiocarcinoma from hepatocellular carcinoma
      in high-risk patients: A predictive model using contrast-enhanced ultrasound.
AB  - AIM: To develop a contrast-enhanced ultrasound (CEUS) predictive model for
      distinguishing intrahepatic cholangiocarcinoma (ICC) from hepatocellular
      carcinoma (HCC) in high-risk patients. METHODS: This retrospective study
      consisted of 88 consecutive high-risk patients with ICC and 88 high-risk patients
      with HCC selected by propensity score matching between May 2004 and July 2016.
      Patients were assigned to two groups, namely, a training set and validation set,
      at a 1:1 ratio. A CEUS score for diagnosing ICC was generated based on
      significant CEUS features. Then, a nomogram based on the CEUS score was
      developed, integrating the clinical data. The performance of the nomogram was
      then validated and compared with that of the LR-M of the CEUS Liver Imaging
      Reporting and Data System (LI-RADS). RESULTS: The most useful CEUS features for
      ICC were as follows: rim enhancement (64.5%), early washout (91.9%), intratumoral
      vein (58.1%), obscure boundary of intratumoral non-enhanced area (64.5%), and
      marked washout (61.3%, all P < 0.05). In the validation set, the area under the
      curve (AUC) of the CEUS score (AUC = 0.953) for differentiation between ICC and
      HCC was improved compared to the LI-RADS (AUC = 0.742) (P < 0.001). When clinical
      data were added, the CEUS score nomogram was superior to the LI-RADS nomogram
      (AUC: 0.973 vs 0.916, P = 0.036, Net Reclassification Improvement: 0.077,
      Integrated Discrimination Index: 0.152). Subgroup analysis demonstrated that the
      CEUS score model was notably improved compared to the LI-RADS in tumors smaller
      than 5.0 cm (P < 0.05) but not improved in tumors smaller than 3.0 cm (P > 0.05).
      CONCLUSION: The CEUS predictive model for differentiation between ICC and HCC in
      high-risk patients had improved discrimination and clinical usefulness compared
      to the CEUS LI-RADS.

PMID- 30197487
TI  - How Au Outperforms Pt in the Catalytic Reduction of Methane towards Ethane and
      Molecular Hydrogen.
AB  - Within the context of a "hydrogen economy", it is paramount to guarantee a stable
      supply of molecular hydrogen to devices such as fuel cells. At the same time,
      catalytic conversion of the environmentally harmful methane into ethane, with a
      significantly lower Global Warming Potential, turns into a highly desirable
      challenge. Herein we propose a first-step novel proof-of-concept mechanism to
      accomplish both tasks simultaneously. For that purpose we provide transition
      state barriers and reaction Helmholtz free energies obtained from first
      principles Density Functional Theory by taking account vibrations for 2CH4(g) ->
      C2H6(g) + H2(g) to show that molecular hydrogen can be produced by subnanometer
      Pt38 and Au38 nanoparticles from natural gas. Interestingly, the active sites for
      the reaction are located on different planes on the two nanoparticles,
      effectively differentiating the working principle of the two metals. The analysis
      shows that the complete cycle to reduce CH4 can be performed on Au and Pt with
      similar efficiencies, but Au requires only half the working temperature of Pt.
      This substantial decrease of temperature can be traced back to several
      intermediate steps, but most crucially to the final one where the catalyst must
      be cleaned from H(?) to be able to restart the catalytic cycle. This simple study
      case provides useful guidelines to capitalize on finite-size effects in small
      nanoparticles for the design of new and more efficient catalysts. Interestingly,
      present results obtained for the intermediate steps of the catalytic cycle show
      an excellent agreement with previous experimental evidence. Finally, we stress
      the importance of including the final cleaning steps to start a new fresh
      catalytic cycle.

PMID- 30197486
TI  - Neurofibromatosis type 1-associated multiple rectal neuroendocrine tumors: A case
      report and review of the literature.
AB  - Neurofibromatosis type 1 (NF-1) is commonly associated with benign or malignant
      tumors in both the central and peripheral nervous systems. However, rare cases of
      NF-1-associated multiple rectal neuroendocrine tumors have been reported. This
      report describes a case of a 39 year old female with NF-1 and intermittent
      hematochezia as a primary symptom. Physical examination showed multiple
      subcutaneous nodules and cafe au lait spots with obvious scoliosis of the back.
      Imaging examinations and colonoscopy found malformation of the left external
      iliac vein and multiple gray-yellow nodules with varying sizes and shapes in the
      rectal submucosal layer. Histological and immunohistochemical results suggested
      multiple rectal neuroendocrine tumors, a rare disease with few appreciable
      symptoms and a particularly poor prognosis. The patient with NF-1 presented here
      had not only multiple rectal neuroendocrine neoplasms but also vascular
      malformations, scoliosis and other multiple system lesions. This case therefore
      contributes to improving clinical understanding, diagnosis and treatment of
      related complications for patients with NF-1 who present with associated medical
      conditions.

PMID- 30197488
TI  - Academic Resilience Despite Early Academic Adversity: A Three-Wave Longitudinal
      Study on Regulation-Related Resiliency, Interpersonal Relationships, and
      Achievement in First to Third Grade.
AB  - Using a bio-social-ecological systems framework, we examined whether
      interpersonal relationships at school (specifically teacher-student and peer
      relationships) mediated the link between child resiliency (temperament-based
      adaptability) and reading or math achievement in a sample of children assessed as
      experiencing early academic adversity. Participants were 784 ethnically diverse
      students (mean age at Year 1 = 6.57 years, SD=0.39) who began school as
      struggling readers or as weak in reading skills relative to their peers (scoring
      below the median on a school-wide standardized literacy exam). Data on children's
      resiliency, teacher-student warmth and conflict, peer social preference and peer
      liking, and reading and math achievement scores were collected across 3 years and
      three-wave longitudinal models of mediation were tested. Accounting for students
      nested within classrooms and for baseline covariates (i.e., ethnicity, social
      economic status, gender), results showed that peer relationships mediated the
      effect of resiliency on reading, but not math, achievement. Teacher-student
      relationships were not found to be a mediator between resiliency and achievement.
      Findings suggest that for children with early academic adversity, resiliency is a
      protective factor against future academic problems with peer competence
      facilitating children's academic engagement and achievement.

PMID- 30197489
TI  - The Increasing Diversity and Complexity of Family Structures for Adolescents.
AB  - The structure of adolescents' families, and thus parental forms, in the United
      States, have become more heterogeneous and fluid over the past several decades.
      These changes are due to increases in never-married, single parents, divorce,
      cohabitation, same-sex parenting, multi-partnered fertility, and co-residence
      with grandparents. We document current diversity and complexity in adolescents'
      families as important context for rethinking future parenting theory and
      research. We also discuss how understandings of adolescents' families are
      somewhat limited by current methods used to measure characteristics of families.
      We recommend social network and profile-based methods as alternatives to
      capturing key dimensions of family structure and processes. Understanding the
      diversity of households and families in which adolescents are raised can improve
      theory and research on parenting.

PMID- 30197490
TI  - Enhancing Relationship Skills and Couple Functioning with Mobile Technology: An
      Evaluation of the Love Every Day Mobile Intervention.
AB  - A research-informed mobile application (app) was created to encourage and
      activate couples to demonstrate healthy relationship behaviors in an effort to
      promote relationship quality, stability, and resilience. The app, Love Every Day,
      is grounded in the literature on couple quality, habit formation, and family
      resilience, and it uses tenets of effective behavioral intervention technologies.
      Forty-three couples (N = 86 participants) engaged with the app across a 21-day
      period and completed online evaluations, which consisted of a pretest, posttest,
      and three weekly questionnaires. Findings suggest that the couples' app promoted
      high levels of engagement, such that most participants viewed the app multiple
      times a day and also submitted answers to daily prompts 19.8 of the 21 days (94%
      of the intervention). Pretest and posttest assessments suggest that participants
      enhanced their relationship skills and behaviors, including knowledge of their
      partner's general well-being, care for one's partner, partner communication, and
      self-efficacy to manage conflict. Participants also reported higher levels of
      relationship quality after engaging with the app for 21 days, including less
      relationship distress, greater partner cohesion, better relationship
      satisfaction, and more relationship confidence. Implications for self-directed
      modes of relationship education and promoting family resilience are discussed.

PMID- 30197491
TI  - Men Who Specifically Seek Unprotected Sex Partners via the Internet: Whose
      Profiles Are the Most Searched for by Other Site Users?
AB  - Men who have sex with men (MSM) account for the largest number of persons
      diagnosed with AIDS in the United States, with higher than-average rates of drug
      use and unprotected sex being cited as the principal reasons underlying their
      high rates of HIV infection. Recent evidence has suggested that the use of Web
      sites specifically designed to promote unsafe sexual practices may be
      particularly common among MSM, therebyfostering their risky behaviots. In light
      of these findings, the present study which compares HIV risk behaviors sought by
      men whose profiles are among the most frequently brought up in searches to those
      whose profiles ate not aspopular with other site users, is based on a content
      analysis of 1,316 ads/profiles posted on one of the most popular MSM Web sites
      that specifically fosters unprotected sex. Ads/profiles were selected randomly
      based on the American ZIP code of residence. Data were collected between
      September 2006 and January 2007. Rates of advertised-for high-risk sexual
      behaviots were very high both for men whose profiles were among the most popular
      and those whose profiles were not, particularly for oral sex involving
      ejaculation into the mouth, anal sex involving ejaculation into the anus,
      multiple partner sex, and fetching. Analytical comparisons of these groups showed
      that the most searched for profiles weae thosepromoting the highest levels
      ofrisky behaviors and the greatest propensity toward wanting to engage in high
      risk activities. Ihe HIV intenention-related implications of these findings are
      discussed.

PMID- 30197493
TI  - Comparing Rotary Bend Wire Fatigue Test Methods at Different Test Speeds.
AB  - Given its relatively simple setup and ability to produce results quickly, rotary
      bend fatigue testing is becoming commonplace in the medical device industry and
      is the subject of a new standard test method ASTM E2948-14. Although some
      research has been conducted to determine if results differ for different rotary
      bend fatigue test setups or test speeds, these parameters have not been
      extensively studied together. In this work, we investigate the effects of these
      two parameters on the fatigue life of three commonly used medical device alloys
      (ASTM F2063 nitinol, ASTM F138 stainless steel, and ASTM F1058 cobalt chromium).
      Results with three different rotary bend fatigue test setups revealed no
      difference in fatigue life among those setups. Increasing test speed, however,
      between 100 and 35,000 RPM led to an increased fatigue life for all three alloys
      studied (average number of cycles to fracture increased between 2.0 and 5.1 times
      between slowest and fastest test speed). Supplemental uniaxial tension tests of
      stainless steel wire at varying strain rates showed a strain rate dependence in
      the mechanical response which could in part explain the increased fatigue life at
      faster test speeds. How exactly strain rate dependence might affect the fatigue
      properties of different alloys at different alternating strain values requires
      further study. Given the difference in loading rates between benchtop fatigue
      tests and in vivo deformations, the potential for strain rate dependence should
      be considered when designing durability tests for medical devices and in
      extrapolating results of those tests to in vivo performance.

PMID- 30197494
TI  - Atypical Clinical Findings in Prader-Willi Syndrome Patients: Analysis of Survey
      Data.

PMID- 30197495
TI  - Underrepresentation and Symbolic Annihilation of Socially Disenfranchised Groups
      ("Out Groups") in Animated Cartoons.
AB  - For many years, the mass media have been accused of providing negative and
      potentially-damaging messages to viewers. Some have complained that the media are
      replete with too much violence while others have lamented on media stereotyping
      of various groups. In this article, the authors examine the issues of
      underrepresentation and symbolic annihilation as they apply to one particular
      medium-namely, animated cartoons-to which people are exposed early in life,
      typically on a regular basis for many years. Our principal research questions are
      (a) To what extent do cartoons underrepresent and/or symbolically annihilate
      social groups that are not considered desirable in society-at-large? (b) Has
      underrepresentation and/or symbolic annihilation changed over time? and (c) When
      social "out groups" are shown, how are they depicted vis-a-vis "in groups"? To
      examine these questions, the authors examine portrayals based on gender, age,
      race, and sexual orientation. The data revealed that animated cartoons have a
      long history of underrepresenting and symbolically annihilating socially devalued
      "out groups" and that little has changed over the course of the past 65+ years.
      When "out group" members are included in cartoons, however, their portrayals tend
      not to be dramatically different-not better and not much worse-than those typical
      of their "in group" counterparts.

PMID- 30197492
TI  - Testing genetic modifiers of behavior and response to atomoxetine in autism
      spectrum disorder with ADHD.
AB  - Background: Frequent non-pathogenic genetic variants may act as moderators of
      phenotypic severity for complex disorders such as autism spectrum disorder (ASD).
      We previously identified polymorphisms affecting mRNA expression of candidate
      genes, including tryptophan hydroxylase 2 (TPH2), dopamine beta hydroxylase
      (DBH), and dopamine transporter (DAT, SLC6A3). Method: We compare genotypes and
      (1) clinical response to atomoxetine, (2) scores from the Autism Diagnostic
      Interview-Revised (ADI-R), and (3) severity of Attention Deficit Hyperactivity
      Disorder (ADHD) symptoms in a cohort of patients with ASD from multiple study
      sites. Results: There was no association between CYP2D6 metabolizer status and
      atomoxetine response. TPH2 rs7305115 genotype was associated with ADI-R
      Restrictive/Repetitive Behavior score (p=0.03). DBH rs1611115 genotype was
      associated with ADI-R Social score (p=0.002) and Restrictive/Repetitive Behavior
      score (p=0.04). The DAT intron 8 5/6 repeat was associated with ADHD symptoms
      (ABC Hyperactivity p=0.01 and SNAP ADHD p=0.03), replicating a previous finding.
      Conclusions: We find associations between ASD phenotypes and regulatory variants
      in catecholamine biosynthesis genes. This work may help guide future genetics
      studies related to ASD.

PMID- 30197496
TI  - Blood pressure, ocular perfusion pressure and open-angle glaucoma in patients
      with systemic hypertension.
AB  - Background: The aim of the study was to evaluate the relationship between blood
      pressure (BP), ocular perfusion pressure (OPP) and occurrence of primary open
      angle glaucoma (POAG) among patients with systemic hypertension. Participants and
      methods: A cross-sectional study of hypertensive patients was conducted in six
      cities in Colombia. The participants underwent a complete ophthalmological
      examination. The intraocular pressure measurement was obtained by Goldmann
      tonometry. The diagnosis of glaucoma was confirmed by visual field and optic
      nerve photos. Interviews and questionnaires were used to evaluate participants'
      lifestyle and other health conditions. A multinomial logistic regression was used
      to assess the relationship between BP, OPP and presence of suspected or confirmed
      POAG. Results: A total of 1,272 individuals were included in this study; 131
      (10.3%) were diagnosed with suspected glaucoma and 65 (5.1%) with confirmed
      glaucoma. High values of diastolic BP (>90 mmHg) and low values of OPP (<40 mmHg)
      were associated to an increased risk of confirmed POAG. The type of
      antihypertensive treatment did not modify these relationships. Conclusion: This
      study suggests that there is a close relationship between OPP and confirmed
      glaucoma in hypertensive patients, providing further evidence of the vascular
      mechanism in glaucoma pathogenesis.

PMID- 30197497
TI  - Real-life results of switching from preserved to preservative-free artificial
      tears containing hyaluronate in patients with dry eye disease.
AB  - Background: Dry eye disease (DED) is a chronic, multifactorial disease of the
      ocular surface leading to discomfort, visual disturbance, and tear film
      instability, with potential damage to the ocular surface. Aim: The aim of this
      study was to assess the clinical benefit of a switch from preserved to
      preservative-free artificial tears (ATs) containing hyaluronate in patients with
      DED. Materials and methods: This is a nationwide, multicenter, noninterventional,
      and transversal observational survey. Results: The mean age was 51.0+/-15.4
      years, ranging from 6 to 96 years. The majority (61.4%) was female. The mean
      Ocular Surface Disease Index (OSDI) before the switch was surprisingly high at
      56.0+/-23.5, and 73.0% of the patients had superficial punctate keratitis (SPK).
      The mean duration of use of preserved ATs before the switch was 15.8+/-12.1
      months. OSDI scores and the presence of SPK correlated with the patients' ages
      but were independent of the duration of treatment with the preserved AT. The
      patients using ATs containing "soft" or "vanishing" preservatives presented
      exactly the same clinical pattern (level of OSDI and frequency of SPK) as those
      using ATs containing classical preservatives such as benzalkonium chloride (BAK).
      After switching to preservative-free AT containing hyaluronate (Hyabak(r)), the
      OSDI of 97.0% of the patients improved, decreasing from an average of 56.0 to an
      average of 28.2, with 23% of patients reporting a normal value of OSDI. The SPK
      frequency as well improved dramatically, with a frequency of positive fluorescein
      staining dropping from 73% to 46.1% of patients. A total of 94.0% of the patients
      considered that they preferred being treated with the preservative-free AT.
      Conclusion: In patients suffering from DED and treated with a preserved AT,
      switching to a preservative-free AT provides clinical benefit by decreasing the
      severity of DED and reducing the prevalence of SPK, even after only 3 weeks of
      daily use of the preservative-free AT.

PMID- 30197498
TI  - New corneal assessment index from the relational thickness and other OCULUS
      values (CAIRO Index).
AB  - Purpose: The aim of this study was to find indices for keratoconus (KC) detection
      with higher sensitivity and specificity than the currently available ones with
      the rotating Scheimpflug imaging (Oculyzer I, Pentacam) software. Patients and
      methods: Data of 103 normal and 73 KC eyes imaged by Oculyzer I, including slit
      lamp examination, refraction, Scheimpflug images, and follow-up data were
      collected. Logistic regression was done to find new indices with higher area
      under receiver operating characteristic curves using the currently available
      ones. Results: The Corneal Assessment Index from Relational thickness and other
      OCULUS Values 9 (CAIRO 9) index, deduced from the Ambrosio relational thickness
      maximum and the anterior elevation at thinnest point from 9 mm best-fit sphere,
      and the CAIRO 8, deduced from Ambrosio relational thickness-maximum and anterior
      elevation at thinnest point from 8 mm best-fit sphere, have a very high area
      under receiver operating characteristic curves for KC detection (0.997 and 0.995,
      respectively). Conclusion: New corneal assessment index is deduced with better
      sensitivity and specificity for KC detection.

PMID- 30197500
TI  - Risk factors for early onset elevated intraocular pressure after pterygium
      surgery.
AB  - Purpose: In this study, we aimed to identify the risk factors for early
      postoperative elevation of intraocular pressure (IOP) after pterygium surgery.
      Patients and methods: All patients in this retrospective cohort study were
      evaluated for inclusion from a single tertiary care center at Boston Medical
      Center. Their pre- and postoperative IOP measurements (day 1, week 1, month 1,
      month 3, and when clinically necessary) were compared. Patients with
      postoperative IOP measurement of >22 mmHg or with an increase in IOP by >=10 mmHg
      compared with the preoperative measurement value were grouped as "Ocular
      Hypertension" group; otherwise, patients were grouped in the "No Ocular
      Hypertension" group. Age, sex, race, baseline IOP, cup-to-disc (C/D) ratio,
      history of glaucoma, and frequency of use of postoperative steroid drops in all
      patients were compared. Chi square test was performed to compare the categorical
      variables, whereas Student's t-test was performed to compare continuous
      variables. We performed a multivariate logistic regression analysis of
      categorical data with a significance level of p < 0.05. Results: In total, 240
      patient charts were reviewed for inclusion in this study. Twenty-six patients
      required pterygium surgery on both eyes; for these patients, the eye with higher
      IOP was analyzed. Two patients were discontinued from this study because of
      elevated IOP in the contralateral, nonsurgical eye. Fortyeight out of 212 eyes
      (22.64%) developed postsurgical elevation of IOP within the first 3 months of
      operation. No significant differences were found between age, sex, baseline IOP,
      C/D ratio, history of glaucoma diagnoses, and frequency of use of postoperative
      steroid drops. However, Hispanic/Latino race (p = 0.036) and lack of application
      of steroid ointment (p = 0.001) were found to be the significant risk factors for
      the development of "Ocular Hypertension" in multivariate analysis. Conclusion:
      Early elevation of IOP is a risk of pterygium surgery. One nonmodifiable risk
      factor, Hispanic/Latino race, and one modifiable risk factor, lack of application
      of steroid ointments, were identified as potential causes of early postoperative
      IOP elevation.

PMID- 30197499
TI  - Evaluation of a smartphone photoscreening app to detect refractive amblyopia risk
      factors in children aged 1-6 years.
AB  - Purpose: To determine the specificity and sensitivity of a smartphone app
      (GoCheckKids [GCK] used as a photoscreening tool on the iPhone 7 to detect
      refractive amblyopia risk factors in children aged 1-6 years. Participants and
      methods: A prospective, multicenter, 10-month evaluation of children aged 1-6
      years old who underwent photoscreening with the GCK app to detect amblyopia risk
      factors. The first acceptable quality photograph of each study subject was
      evaluated by trained technicians using GCK's proprietary automated image
      processing algorithm to analyze for amblyopia risk factors. Trained graders,
      masked to the cycloplegic clinical data, remotely reviewed photographs taken with
      the app and compared results to the gold standard pediatric ophthalmology
      examinations using the 2013 American Association for Pediatric Ophthalmology &
      Strabismus amblyopia risk factor guidelines. Primary outcome was the ability of
      the GCK app to identify amblyopia risk factors compared to the cycloplegic
      refraction. Results: There were 287 patient images analyzed. The overall
      sensitivity and specificity in detecting amblyopia risk factors were 76% and 85%,
      respectively using manual grading. The overall automated grading results had a
      sensitivity and sensitivity in detecting amblyopia risk factors of 65% and 83%,
      respectively. Conclusion: The GCK smartphone app is a viable photoscreening
      device for the detection of amblyopia risk factors in children aged 1-6 years.

PMID- 30197501
TI  - A randomized, double-blind clinical trial of canrenone vs hydrochlorothiazide in
      addition to angiotensin II receptor blockers in hypertensive type 2 diabetic
      patients.
AB  - Aim: The aim of this study was to evaluate the effects of canrenone compared to
      hydrochlorothiazide (HCTZ) added to angiotensin II receptor blockers (ARBs) on
      glycemia, lipid profile, potassium, aldosterone and renal function in patients
      with hypertension and type 2 diabetes mellitus. Patients and methods: The study
      enrolled 182 Caucasian patients with hypertension and type 2 diabetes mellitus.
      Patients were already taking ARBs and were randomized to canrenone, 50 mg once a
      day, or HCTZ, 12.5 mg once a day for 1 month. After the first month, patients not
      reaching an adequate blood pressure (BP) were up-titrated to canrenone 100 mg or
      HCTZ 25 mg once a day for 12 months. The following parameters were considered at
      6 and 12 months: BP, body weight, body mass index (BMI), fasting plasma glucose
      (FPG), post-prandial glucose (PPG), fasting plasma insulin (FPI), homeostasis
      model assessment insulin (HOMA-IR), lipid profile, potassium, plasma aldosterone,
      urine albumin excretion rate and estimated glomerular filtration rate (eGFR).
      Results: We observed a similar decrease in BP with both treatments. Canrenone led
      to a significant decrease in FPG, PPG and HOMA index compared to baseline, while
      there was a significant increase in the same parameters with HCTZ. HCTZ also
      worsened glycated hemoglobin (HbA1c), while canrenone did not change it. No
      variations in lipid profile were recorded with canrenone, while there was a
      worsening of total cholesterol (TC) and triglycerides (Tg) with HCTZ. Potassium
      levels were decreased and uric acid levels were increased by HCTZ, but not by
      canrenone that had a neutral effect on these parameters. We recorded a slight
      decrease in eGFR with HCTZ and an improvement with canrenone; creatinine and eGFR
      were improved by canrenone compared to HCTZ. Plasma aldosterone levels were
      decreased by canrenone and increased by HCTZ. Conclusion: Canrenone and HCTZ have
      a similar effect on BP; however, canrenone seems to improve metabolic parameters,
      while HCTZ worsens them.

PMID- 30197502
TI  - Predictors of medication nonadherence in patients with systemic lupus
      erythematosus in Sichuan: a cross-sectional study.
AB  - Purpose: The aim of this study was to determine the prevalence and predictors of
      medication nonadherence among patients with systemic lupus erythematosus (SLE) in
      Sichuan. Patients and methods: A cross-sectional investigation was performed.
      Participants were recruited by consecutive sampling from the Rheumatic Clinic of
      a university hospital between June and September 2016. Patients' self-reported
      medication adherence was assessed by the eight-item Morisky Medication Adherence
      Scale. Additional surveys included patients' demographics, and clinical and
      treatment characteristics. Logistic regression analysis was used to identify the
      predictors of medication nonadherence. Results: A total of 140 patients were
      included in analysis. The percentage of patients classified as nonadherent to
      medication was 75%. Low education, rural residency, childlessness, limited
      comprehension of medication instructions, side effects experienced,
      dissatisfaction with treatment and better physical health were associated with an
      increased risk of nonadherence. Conclusion: This study demonstrated a high
      prevalence of medication nonadherence among SLE patients in Sichuan, and factors
      associated with the nonadherence are multifaceted. Interventions for these
      factors, such as appropriate adjustment of the service resources for patients
      with rheumatic disease in rural communities and improved communication between
      the health care providers and the patients, may contribute to improve the
      medication adherence of this cohort.

PMID- 30197503
TI  - Portable coagulometer for vitamin K-antagonist monitoring: the patients' point of
      view.
AB  - Purpose: The aim of this study was to know the patients' point of view on the
      monitoring of vitamin K-antagonist (VKA) therapy by means of a point of care
      testing (POCT), ie, using a portable coagulometer by self-testing at home. At
      first, patients had prothrombin time (PT) international normalized ratio (INR)
      monitoring at a thrombosis center; afterward, they were shifted to self-testing
      at home. An interview was done to evaluate the patients' point of view on the two
      monitoring periods. Patients and methods: A total of 92 oral anticoagulated
      patients were enrolled. The questionnaire contained nine questions that elicited
      a maximum of five closer answers that were arranged in increasing levels of
      satisfaction: very little, little, enough, much and completely. Percentage of
      time in therapeutic range (TTR) and adverse events were compared during the two
      periods of conventional monitoring and self-testing. Results: The period of
      conventional monitoring was shorter than that of self-testing (p<0.0001), and the
      median TTR was satisfactory but lower than that of self-testing (p<0.0001). A
      total of 85% of the patients were satisfied with self-testing at home. In all,
      83% and 73% (p=0.06) of patients felt comfortable about side effects while
      measuring the PT INR at both home and the thrombosis center, respectively. During
      the self-testing period, quality of life was improved in 87% of the patients. The
      cost of test strips was medium-high for 89% of the patients, and 75% of them
      stated that it was worth improving their quality of life. A switch from VKA to a
      direct oral anticoagulant (DOAC) was proposed to 24% of the patients, but 68% of
      them declined because they felt more comfortable monitoring their oral
      anticoagulant therapy by POCT. Conclusion: VKA monitoring using POCT at home may
      play a role in improving the patients' quality of life and may be considered as
      an alternative to the use of DOAC at least in certain settings of patients.

PMID- 30197505
TI  - A discrete choice experiment on preferences of patients with rheumatoid arthritis
      regarding disease-modifying antirheumatic drugs: the identification, refinement,
      and selection of attributes and levels.
AB  - Objective: To comprehensively describe the identification, refinement, and
      selection of attributes and levels for a discrete choice experiment (DCE) on
      preferences of patients with rheumatoid arthritis (RA) regarding disease
      modifying antirheumatic drugs (DMARDs). Methods: A mixed-methods approach,
      consisting of three consecutive steps: a literature review, expert
      recommendations, and focus groups. Attributes and levels were identified by a
      scoping review and compiled into a list that was evaluated on its relevance by an
      expert panel. The list that resulted thereafter was used to inform three focus
      groups, including 23 patients with RA. New attributes and levels could be
      identified during the focus groups. Also, a ranking exercise was performed. The
      patients individually ranked the attributes (ie, the ones on the list and newly
      identified attributes) by relevance. The patients' individual rankings were
      summed to derive a ranking at group level and make an a priori selection of the
      most relevant attributes. The group discussions were transcribed for qualitative
      analysis. Results: Nineteen attributes, each specified by two to seven levels,
      were identified by the scoping review. The expert recommendations resulted in the
      removal of one attribute. Furthermore, two new attributes and levels were
      identified and two attributes were split into two. One new attribute was
      identified during the focus groups. The results of the ranking exercise and
      qualitative analysis led to the refinement and selection of the following
      attributes: route of administration, frequency of administration, chance of
      efficacy, onset of action, risk of serious infections, risk of liver injury, and
      risk of cancer. Each attribute was specified by three levels. Conclusion: This
      study contributes to the limited literature on the development of attributes and
      levels. Future research should pay more attention to a comprehensive description
      of this process. It ensures transparency and thereby allows researchers to judge
      a DCE's quality and generalizability.

PMID- 30197504
TI  - A perspective on nonadherence to drug therapy: psychological barriers and
      strategies to overcome nonadherence.
AB  - Medication adherence represents an inefficiency and ongoing challenge within
      medical care. The problem has been long-recognized - indeed, the research
      literature contains thousands of articles on the topic. Nonetheless, because of
      the complex nature of the problem, it still cannot be considered to be solved.
      Reasons for nonadherence are myriad but psychological barriers to adherence are
      most difficult to mitigate and, thus, are the focus of this paper. The present
      narrative review sketches a summary of theoretical models commonly utilized to
      understand and help address medication nonadherence; uses a patient-centered care
      approach to contextualize the problem of nonadherence to drug therapies; and then
      outlines a set of best-practice recommendations based on the extant data and
      framed from the perspective of the Information-Motivation-Strategy model.

PMID- 30197506
TI  - Adherence to disease-modifying therapies in patients with multiple sclerosis.
AB  - Background: Multiple sclerosis (MS) is a chronic, inflammatory progressive
      demyelinating disease of the central nervous system. MS is one of the main causes
      of disability among young adults, and its management is a serious challenge for
      the healthcare system. Purpose: The main purpose of this study was to examine
      adherence to first-line disease-modifying therapy (DMT) in MS patients using the
      self-report Multiple Sclerosis Treatment Adherence Questionnaire (MS-TAQ).
      Materials and methods: The participants consisted of 226 MS patients (166 women
      and 60 men) who were treated with first-line immunomodulatory DMT. This study
      used a questionnaire designed by the authors, which contained questions about
      sociodemographic data, and the Polish version of the MS-TAQ. Results: The overall
      adherence was 76.5% according to the first criterion (missed >=1 injection or
      tablet). There were no statistically significant differences due to
      sociodemographic variables between adherent and nonadherent patients. However,
      patients taking Avonex(r) significantly more often belonged to the adherent group
      (P=0.042). The most frequently mentioned reasons why nonadherent patients forget
      to take the drug included the following: too busy in their daily activities,
      indisposition to take the drug, unwillingness to take the drug, interference with
      daily activities, and dissatisfaction with the drug. The degree of adherence
      among MS patients treated with immunomodulatory drugs is high; however, some
      patients do not take medications regularly. Conclusion: Due to the utility of the
      MS-TAQ, the caregivers of MS patients are able to quickly and easily assess the
      occurrence of side effects, ways to cope with them, and the occurrence of
      barriers to taking medication.

PMID- 30197507
TI  - The impact of first and second eye cataract surgeries on falls: a prospective
      cohort study.
AB  - Purpose: The purpose of this study was to investigate the impact of the first and
      second eye cataract surgeries on the risk of falls in participants with bilateral
      cataract and to determine which changes in visual measures are associated with
      changes in the number of falls throughout the cataract surgery process. Patients
      and methods: Fifty-five older adults with bilateral cataract aged 55+ years were
      assessed at three time points during the cataract surgery process, and they
      completed a falls diary. Two separate generalized estimating equation-negative
      binomial models were undertaken to assess changes in the number of falls before
      first eye cataract surgery, between first and second eye surgeries, and after
      second eye cataract surgery and which changes in visual measures were associated
      with changes in the number of falls. Results: After adjusting for potential
      confounding factors, the risk of falls decreased by 54% (incidence rate ratio
      (IRR) =0.458, 95% CI=0.215-0.974, p=0.04) after first eye cataract surgery only,
      compared with the period before first eye surgery. The risk of falls decreased by
      73% (IRR =0.268, 95% CI =0.114-0.628, p=0.002) after second eye cataract surgery,
      compared with the period before first eye surgery. Improved binocular visual
      acuity (IRR =5.488, 95% CI =1.191-25.282, p=0.029) and contrast sensitivity (IRR
      =0.257, 95% CI =0.070-0.939, p=0.040) were associated with a decrease in the
      number of falls. Conclusion: The study found that first and second eye cataract
      surgeries reduced the risk of falls among a cohort of bilateral cataract patients
      with relatively good baseline vision. This suggests that timely first and second
      eye cataract surgeries could play an important role in reducing the burden due to
      falls among older adults with cataract.

PMID- 30197508
TI  - Glucocorticoid-induced delayed fracture healing and impaired bone biomechanical
      properties in mice.
AB  - Background: The objective of the study was to investigate the effects of
      glucocorticoid (GC) on the fracture healing process in a closed femur fracture
      mice model. Materials and methods: Forty 12-week-old female CD-1 mice were
      randomly allocated into four groups: healthy control and mice with prednisone
      exposure (oral gavage), 6 mg/kg/day (GC-L), 9 mg/kg/day (GC-M) and 12 mg/kg/day
      (GC-H). Three weeks after the initiation of prednisone dosing, closed femur
      fractures were created on prednisone-exposed mice and the healthy control.
      Prednisone administration was continued for 9 weeks post-fracture, and X-ray
      imaging was performed weekly to monitor the fracture healing process until the
      mice were euthanized. Necropsy was performed after 9 weeks and the fractured
      femurs were isolated and processed at necropsy for micro-CT and biomechanical
      property analysis. Another 20 mice (control and GC-H, 10 mice/group) were used
      for histology and micro-CT analysis at early time point (2-week post fracture)
      with continued prednisone exposure. Results: The results showed that oral
      administration of prednisone for 3 months in this strain of mice could inhibit
      endochondral ossification and delay the healing process, especially hard callus
      formation (woven bone) and bone remodeling during healing. It also could
      significantly decrease bone biomechanical properties. Conclusion: Long-term GC
      administration leads to significantly delayed fracture healing and impaired bone
      biomechanical properties. This mouse model may be used to systematically study
      the cellular and molecular mechanisms underlying fracture healing with GC
      treatment background and may also be used to study the influence of different
      therapeutic interventions for bone fracture healing.

PMID- 30197510
TI  - Health effects in COPD smokers who switch to electronic cigarettes: a
      retrospective-prospective 3-year follow-up.
AB  - Background: Health effects of electronic cigarette (EC) use in patients with
      chronic obstructive pulmonary disease (COPD) are largely unexplored. Aim: We
      present findings from a long-term prospective assessment of respiratory
      parameters in a cohort of COPD patients who ceased or substantially reduced
      conventional cigarette use with ECs. Methods: We prospectively re-evaluated COPD
      exacerbations, spirometric indices, subjective assessments (using the COPD
      Assessment Tool [CAT] scores), physical activity (measured by the 6-minute walk
      distance [6MWD]), and conventional cigarette use in EC users with COPD who were
      retrospectively assessed previously. Baseline measurements prior to switching to
      EC use were compared to follow-up visits at 12, 24, and 36 months. Age- and sex
      matched regularly smoking COPD patients who were not using ECs were included as
      reference (control) group. Results: Complete data were available from 44
      patients. Compared to baseline in the EC-user group, there was a marked decline
      in the use of conventional cigarettes. Although there was no change in lung
      function, significant improvements in COPD exacerbation rates, CAT scores, and
      6MWD were observed consistently in the EC user group over the 3-year period
      (p<0.01). Similar findings were noted in COPD EC users who also smoked
      conventional cigarettes ("dual users"). Conclusion: The present study suggests
      that EC use may ameliorate objective and subjective COPD outcomes and that the
      benefits gained may persist long-term. EC use may reverse some of the harm
      resulting from tobacco smoking in COPD patients.

PMID- 30197509
TI  - Low bone mineral density is associated with global coronary atherosclerotic
      plaque burden in stable angina patients.
AB  - Background: Accelerated atherosclerosis is considered to be the linking factor
      between low bone mineral density (BMD) and increased cardiovascular events and
      mortality, while some coronary angiographic studies do not support this point. In
      this study, we attempt to provide a distinct comprehensive view of the
      relationship between BMD and the angiographically determined coronary
      atherosclerotic burden. Methods: A total of 459 consecutive patients with stable
      chest pain suspected of coronary artery disease (CAD) underwent both dual-energy
      X-ray absorptiometry scan and selective coronary angiography. The association
      between BMD and global coronary atherosclerotic plaque burden as represented by
      the multivessel involvement and the modified Gensini score was analyzed. Results:
      Multivariable analysis revealed that the low BMD at femoral neck and total hip
      was an independent correlate of multivessel CAD. The T-scores measured at femoral
      neck and total hip were both negatively and independently associated to the
      modified Gensini score. These inversely correlated relationships between BMD and
      CAD were not observed at lumbar spine 1-4. Conclusion: This cross-sectional study
      elucidated an inverse relationship between hip BMD and the modified Gensini
      score, and low hip BMD values (T-scores) were significantly and independently
      associated with increased risk of multivessel coronary disease in patients
      hospitalized for stable chest pain.

PMID- 30197511
TI  - Influence of body mass on predicted values of static hyperinflation in COPD.
AB  - Introduction: For interpretation of body plethysmographic static hyperinflation,
      reference values are of crucial importance. Earliest reference values have been
      published by the European Coal and Steel Community (ECSC) and are based on sex,
      body height and age as predictors. As obesity can lead to a reduction of
      functional residual capacity (FRC) in lung-healthy subjects, more recent
      approaches included body weight or body surface area. This raises the question
      whether these models are appropriate in patients with COPD-induced
      hyperinflation. Method: Several FRC prediction models and their relation to body
      weight were analyzed in 1513 patients with stable COPD (mean [SD] age: 64.5 [8.2]
      years; GOLD grades 1-4: 219/722/484/88), a subset of the multicenter COPD and
      Systemic Consequences - Comorbidities Network cohort. Results: Absolute values of
      FRC were inversely related to body mass index (p<0.001). Applying the ECSC
      equations to calculate predicted values, this pattern was maintained (p<0.001).
      By contrast, an inverted, ie, positive, relation occurred when using equations
      that include body weight or surface area (p<0.001). The present analysis
      confirmed the inverse relation of body mass and FRC in COPD, resulting from a
      restrictive ventilatory pattern by diaphragm elevation and decreased chest wall
      compliance in obesity. The weight influence in the prediction models, as obtained
      from lung-healthy controls, appears to lead to an overcorrection and consequently
      to an inappropriate overestimation of hyperinflation as indicated by FRC
      %predicted in COPD. Conclusion: It is concluded that models not including body
      weight as predictor, like the classical ECSC equations, could be superior in the
      interpretation of FRC in COPD.

PMID- 30197512
TI  - Dual bronchodilation vs triple therapy in the "real-life" COPD DACCORD study.
AB  - Background: No observational studies have evaluated the "real-world"
      effectiveness of dual bronchodilation comprising a long-acting beta2-agonist plus
      a long-acting muscarinic antagonist vs that of triple therapy (long-acting beta2
      agonist plus long-acting muscarinic antagonist plus inhaled corticosteroid) in
      COPD. Materials and methods: DACCORD is a non-interventional, observational
      clinical study that recruited patients following COPD maintenance therapy
      initiation or change in maintenance therapy between or within therapeutic class.
      Given the non-interventional nature of the study, the decision to initiate or
      change medication had to be made by the patients' physicians prior to inclusion
      in DACCORD. We used a matched-pairs analysis to compare disease progression in
      two patient groups: those receiving dual bronchodilation vs those receiving
      triple therapy (each group n=1,046). Results: In two subgroups of patients
      matched according to a broad range of demographic and disease characteristics,
      over 1 year, fewer patients receiving dual bronchodilation exacerbated than those
      receiving triple therapy (15.5% vs 26.6%; P<0.001), with a greater improvement
      from baseline in COPD Assessment Test total score at 1 year (mean+/-SD -2.9+/-5.8
      vs -1.4+/-5.5;P<0.001). When analyzed according to prior therapy, the highest
      rate of exacerbations was in patients on triple therapy prior to the study who
      remained on triple therapy. Those changing from mono-bronchodilator to dual
      bronchodilation had the greatest COPD Assessment Test total score improvement.
      Conclusion: In this "real-life" cohort of patients with COPD, most of whom had
      not exacerbated in the 6 months prior to entry, triple therapy did not seem to
      improve outcomes compared with dual bronchodilation in terms of either
      exacerbations or health status. Our analyses clearly demonstrate the potential
      impact of prior medication on study results, something that should be taken into
      account when interpreting the results even of controlled clinical trials.

PMID- 30197513
TI  - IL-26 in the induced sputum is associated with the level of systemic
      inflammation, lung functions and body weight in COPD patients.
AB  - Background: Chronic inflammatory process is the main link in COPD pathogenesis,
      which causes structural changes in the respiratory tract and lungs. In overweight
      patients, an adipose tissue could contribute to activation of the inflammatory
      process. Therefore, it is highly important to identify potential biomarkers of
      inflammation for patients with COPD and obesity. The aim of this study was to
      investigate the role of interleukin-26 (IL-26) and evaluate the relationship
      between the level of systemic inflammation, lung function, and body mass index
      (BMI) in patients with COPD. Patients and methods: Eighty-three patients with
      COPD in the stable condition (stage 2 according to the 2016 Global Initiative for
      Chronic Obstructive Lung Disease recommendations), aged 40-70 years, were
      included in the study. All patients were divided into 2 groups: obese (n=53) (BMI
      - 30.0-39.9 kg/m2) and non-obese (n=30) (BMI - 18.5-24.9 kg/m2). We conducted
      patients' examination, spirometry, induced the sputum, determined the level of C
      reactive protein (CRP), leptin in serum and IL-26 in sputum. Results: Obese and
      non-obese COPD patients had a significant increase in IL-26 compared with healthy
      subjects by 2.3 and 2.6 (P=0.0003). We also observed a higher level of CRP by
      1.38 times (P=0.0008), compared with the rate in non-obese COPD patients, and by
      1.8 times (P=0.015) higher concentration level of leptin compared with healthy
      subjects. The sputum IL-26 level had positive correlation with BMI, CRP, and
      leptin, and a negative - with forced expiratory volume in 1 second (FEV1) and
      FEV1/forced vital capacity. Leptin level had positive correlation with BMI and
      CRP, and negative with FEV1, FEV1/forced vital capacity. Conclusion: Obese COPD
      patients had a higher level of persistent systemic inflammation than non-obese
      ones, which is confirmed by a significant increase of CRP and leptin in serum.
      The data confirm that IL-26 can be considered as a perspective marker to detect
      the inflammation level in lung tissue of COPD patients.

PMID- 30197514
TI  - Magnetic nanoparticle hyperthermia potentiates paclitaxel activity in sensitive
      and resistant breast cancer cells.
AB  - Introduction: Overcoming resistance to antimitotic drugs, such as paclitaxel
      (PTX), would represent a major advance in breast cancer treatment. PTX induces
      mitotic block and sensitive cells exit mitosis dying by mitotic catastrophe.
      Resistant cells remain in block and continue proliferation after drug decay,
      denoting one of the PTX resistance mechanisms. Mild hyperthermia (HT) triggers
      mitotic exit of PTX-pretreated cells, overcoming PTX resistance and suggesting HT
      forced mitotic exit as a promising strategy to potentiate PTX. Methods and
      results: Superparamagnetic iron oxide nanoparticles (SPIONs) were used to deliver
      mild HT at 42 degrees C in PTX-pretreated breast adenocarcinoma MCF-7 cells
      sensitive and resistant to PTX. To evaluate mechanism of cell death, cells were
      classified based on nuclear morphology into interphase, mitotic, micronucleated,
      and apoptotic. The combined PTX->SPION treatment resulted in an increase in the
      percentage of micronucleated cells, an indication of forced mitotic exit.
      Importantly, in PTX-resistant cells, the combination therapy using SPION HT helps
      to overcome resistance by reducing the number of cells relative to the control.
      Conclusion: SPION HT potentiates PTX by significantly reducing cell survival,
      suggesting potential of combined treatment for future clinical translation.

PMID- 30197515
TI  - Diagnosis of rubella virus using antigen-conjugated Au@Pt nanorods as nanozyme
      probe.
AB  - Background: As nanotechnology advances rapidly, the nanozymes which could replace
      protein enzymes in bioanalytical assays bring a new opportunity to the
      development of simple and sensitive diagnostic tools. Purpose: Antibody
      conjugated Au-Pt core/shell nanorods (Au@Pt NRs) have been used for nanozyme
      probes for diagnosis of rubella virus. Au@Pt NRs, prepared by Au nanorod-mediated
      growth, exhibit peroxidase-like activities and could serve as an inexpensive
      replacement for horseradish peroxidase (HRP) in conjugation of antigen. Method:
      Using a capture enzyme-linked immunosorbant assay for the determination of
      rubella virus. Results: Compared with antibody-conjugated HRP, the antigen
      conjugated Au@Pt NRs are more stable and more robust, but less expensive. Based
      on the enhanced catalytic properties of this nanozyme probe, it was found that
      the antigen-conjugated Au@Pt NRs-based enzyme-linked immunosorbant assay
      exhibited good sensitivity. Conclusion: Our results indicate that these antigen
      conjugated Au@Pt NRs represent a suitable nanozyme probe for future clinical
      applications under various conditions.

PMID- 30197516
TI  - Fabrication of ultra-small monolayer graphene quantum dots by pyrolysis of
      trisodium citrate for fluorescent cell imaging.
AB  - Background: The preparation and biological applications of ultra-small graphene
      quantum dots (GQDs) with accurate-controlled size are of great significance.
      Methods: Here in, we report a novel procedure involving pyrolysis of trisodium
      citrate and subsequent ultrafiltration for fabricating monolayer GQDs with ultra
      small lateral size (1.3+/-0.5 nm). Results: The GQDs exhibit blue
      photoluminescence with peak position independent of excitation wavelength. The
      quantum yield of GQDs is measured to be 3.6%, and the average fluorescence
      lifetime is 2.78 ns. Conclusion: Because of high stability and low toxicity, GQDs
      are demonstrated to be excellent bioimaging agents. The ultra-small GQDs can not
      only distribute in the cytoplasm but also penetrate into the nuclei. We ensure
      that this work will add a new dimension to the application of graphene materials
      for nanomedicine.

PMID- 30197517
TI  - ESSENCE-Q: Slavic language versions for developmental screening in young
      children.
AB  - Purpose: The Early Symptomatic Syndromes Eliciting Neurodevelopmental Clinical
      Examinations - Questionnaire (ESSENCE-Q) was developed as a brief screener to
      identify children with developmental concerns who might have neurodevelopmental
      disorders (NDDs). This study aimed to translate the ESSENCE-Q into south Slavic
      languages, namely, Bosnian, Bulgarian, Croatian, Macedonian, Montenegrin,
      Serbian, and Slovenian, and to evaluate its psychometric properties for screening
      purposes in clinical settings. Patients and methods: In the study, the ESSENCE-Q
      was completed for 251 "typically developing" children and 200 children with 1 or
      more diagnosed NDDs, all aged 1-6 years. Internal consistency and construct
      validity were tested first, followed by generating receiver operating
      characteristic curves and the area under the curve. Optimal cutoff values were
      then explored. Results: The Cronbach's alpha coefficients were 0.91, 0.88, and
      0.86 for ESSENCE-Q parent-completed form, and the telephone and direct interview
      forms administered by trained nurse or specialist, respectively. The 3 versions
      produced area under the curve values (95% confidence interval): 0.96 (0.93-0.99),
      0.91 (0.86-0.95), and 0.91 (0.86-0.97), respectively. An optimal cutoff for
      ESSENCE-Q parent-completed form was found to be >=3 points, while for the
      telephone and direct interviews, it was >=5 points. Conclusion: We found adequate
      measurement properties of the south Slavic languages versions of the ESSENCE-Q as
      a screener for NDDs in clinical settings. This study provided additional data
      supporting sound psychometric properties of the ESSENCE-Q.

PMID- 30197518
TI  - The relationship of individual social activity and cognitive function of
      community Chinese elderly: a cross-sectional study.
AB  - Background: The prevention of cognitive impairment is a crucial public health
      issue, and leisure activities have been studied as the strategy of the cognitive
      preservation. The aim of the study was to explore the possible relationship
      between social activity and cognitive function among community-dwelling Chinese
      elderly in two big cities of Southern China. Participants and methods:
      Altogether, 557 nondemented older adults aged 60 years and older (73.4+/-6.5
      years) were recruited in the social centers in Hong Kong and Guangzhou. A leisure
      activity questionnaire was used to measure the social activity participation.
      Cognitive function was examined using a neuropsychological battery. The
      association between social activity and cognitive function was analyzed using the
      multiple linear regression analysis. Results: Social activities had a weak
      relationship with cognitive performance when measured in terms of overall
      participation. Attending an interest class had significant association with the
      Cantonese version of Mini Mental State Examination, the word list learning test,
      the delayed recall test, and the trail making test. Religious activity showed
      significant association with the word list learning test and the digit vigilance
      test. Singing had significant association with the Category Verbal Fluency Test
      (CVFT) and the trail making test. Conclusion: Some individual social activity
      items may be associated with better cognitive function among the community
      Chinese elderly independently of other factors.

PMID- 30197519
TI  - Epicardial adipose tissue volume is associated with non-alcoholic fatty liver
      disease and cardiovascular risk factors in the general population.
AB  - Background: Epicardial adipose tissue (EAT) is considered an important source of
      bioactive molecules that can influence coronary arteries directly and is related
      to the concurrent presence of both obstructive coronary stenosis and myocardial
      ischemia independently. Non-alcoholic fatty liver disease (NAFLD) has become an
      emergent health problem worldwide. Aim: This cross-sectional study aimed to
      address the relationship between the volume of EAT and NAFLD and other
      cardiovascular risk factors in the general population. Materials and methods: In
      this study, we selected a total of 2,238 participants aged at least 40 years from
      the Jidong community in Tangshan, China. The 64-slice CT was used to survey the
      volume of EAT and liver ultrasonography was used for the diagnosis of NAFLD. The
      study cohorts were compared according to EAT volume. Results: Cardiovascular risk
      factors, such as coronary artery calcium score, carotid intima-media thickness,
      NAFLD, and ideal cardiovascular health metrics were also found to be related to
      EAT. In multivariate logistic regression analysis, NAFLD groups showed
      significant association with higher EAT volume, after correcting for main
      cardiovascular disease risk factors (OR [95% CI], 1.407 [1.117, 1.773]).
      Conclusion: Our findings in a general community population provide evidence that
      EAT is strongly associated with NAFLD and other cardiovascular risk factors.

PMID- 30197521
TI  - Effect of lncRNA ANRIL silencing on anoikis and cell cycle in human glioma via
      microRNA-203a.
AB  - Background: Glioma is a deadly nervous system tumor with a poor prognosis.
      Although there have been many efforts to overcome glioma, the molecular mechanism
      of its pathogenesis remains unclear. Methods: We used human glioma U251 cells
      silenced for the oncogenic lncRNA ANRIL or overexpressing the anti-oncogene miR
      203a to examine the role of lncRNA ANRIL silencing on anoikis and cell cycle
      arrest by flow cytometry. Meanwhile, the activity of caspase-3/8/9 was measured
      by fluorometric assay, the expression of tumor-related genes and activity of AKT
      signaling pathway was measured by Western blotting, real-time PCR, and dual
      luciferase reporter gene assay. Results: lncRNA ANRIL was positively correlated
      with glioma grade and negatively correlated with miR-203a. lncRNA ANRIL silencing
      could induce anoikis and cell cycle arrest in G0/G1 phase, while regulating the
      activity of caspase-3/8/9 and the AKT signaling pathway, and the expression of
      tumor-related genes in the U251 cell line. miR-203a mimics could partially
      reverse these functions. Conclusion: We consider that lncRNA ANRIL is a potential
      therapeutic and diagnostic target for glioma, and miR-203a plays an important
      role in the biological function of lncRNA ANRIL in glioma.

PMID- 30197520
TI  - Effect of continuous positive airway pressure on allergic rhinitis in patients
      with obstructive sleep apnea-hypopnea syndrome.
AB  - Background: The effect of continuous positive airway pressure (CPAP) on nasal
      symptoms in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS)
      remains controversial. In addition, possible mechanism(s) remains unclear.
      Objective: To examine whether CPAP contributes to the onset and exacerbation of
      allergic rhinitis (AR) in OSAHS patients based on patient-reported changes in
      nasal symptoms with and without CPAP therapy and the detection of house dust
      mites (HDMs) in CPAP filters and household environments. Materials and methods:
      In a cohort of OSAHS patients, 350 patients who were undergoing CPAP therapy and
      100 patients who declined CPAP therapy were retrospectively analyzed. These
      patients were contacted by telephone and asked to compare their nasal symptoms
      before and after CPAP therapy. HDMs in air conditioner and CPAP device filters
      and in household dust samples were detected using enzyme-linked immunosorbent
      assays. Results: The prevalence of AR was higher in the CPAP group vs the non
      CPAP group (15.8% vs 7.0%, respectively; P = 0.025). The onset of AR among the
      OSAHS patients with no previous history of AR significantly increased within the
      first year of CPAP therapy compared with the control group (5.7% vs 0%,
      respectively; P = 0.031). Meanwhile, the patients with a history of AR were more
      likely to experience exacerbated rhinitis symptoms within the second year of
      treatment compared with the control group (7.5% vs 0%, respectively; P = 0.005).
      There was no significant difference in HDM concentrations between the CPAP and
      air conditioner filters, yet the concentrations in both the filters were higher
      than the concentrations in the bedroom dust samples (all P < 0.05). Conclusion:
      CPAP is associated with the onset and exacerbation of AR in OSAHS patients. Long
      term exposure to high concentrations of HDM allergens may be a significant
      factor.

PMID- 30197522
TI  - MiRNA-16 inhibited oral squamous carcinoma tumor growth in vitro and in vivo via
      suppressing Wnt/beta-catenin signaling pathway.
AB  - Background: Oral carcinoma, one of the most commonly diagnosed cancers, has a
      poor prognosis and low survival rate with treatment. In recent years, some
      studies reported the upregulation of miRNA-16 (miR-16) in the oral carcinoma,
      whereas some other studies confirmed the downregulation of miR-16. In the current
      study, we aimed to investigate the function of miR-16 in oral carcinoma.
      Materials and methods: Cell proliferation assay was measured by MTT assay,
      quantitative real time polymerase chain reaction (qRT-PCR) was used to evaluate
      the expression of miR-16, and apoptosis was analyzed by flow cytometry. In
      addition, the expression of proteins was detected by Western blot. Moreover,
      xenograft tumor model was established to detect the effect of miR-16 in vivo.
      Results: The results suggested that miR-16 was downregulated in the oral
      carcinoma tissues. Overexpression of miR-16 inhibited the growth and
      proliferation of oral squamous carcinoma cells (OSCCs) and induced apoptosis both
      in vitro and in vivo, which is due to the suppression of Wnt/beta-catenin
      signaling pathway. Conclusion: This study provides evidence that overexpression
      of miR-16 inhibits OSCC growth by regulating Wnt/beta-catenin signaling. Our
      findings suggest that overexpression of miR-16 could be a potential approach for
      gene therapy of OSCC in future.

PMID- 30197523
TI  - Synergistic antitumoral efficacy of a novel replicative adenovirus SG611-PDCD5
      and daunorubicin in human leukemic cells.
AB  - Background: Daunorubicin is a traditional chemotherapeutic agent that plays a
      pivotal role in leukemia therapy. However, the dose-related toxicity remains a
      considerable challenge. The apoptosis-regulating gene, PDCD5, is downregulated in
      various tumors, including leukemias, and may provide a potential target for the
      diagnosis and treatment of leukemia. The purpose of this study was to construct a
      triple-regulated oncolytic adenovirus carrying a PDCD5 gene expression cassette
      (SG611-PDCD5) and explore the combined antitumor efficacy of SG611-PDCD5 in
      combination with low dose daunorubicin on leukemic cells. Materials and methods:
      A variety of leukemic cell lines, including K562, MEG-01, KG-1a, HL-60, SUP-B15,
      and BV-173, were cultured according to the providers' instructions. The insertion
      and orientation of all recombined plasmids were confirmed by restriction enzyme
      digestion and PCR. The tumor-selective replication of the constructed
      conditionally replicating SG611-PDCD5 and its antitumor efficacy in combination
      with daunorubicin were characterized in leukemic cell lines in vitro and in a
      nude mouse xenograft model. Cell viability was detected using cell-counting kit
      8. Apoptosis was detected in whole living cells using flow cytometry and in
      paraffin-embedded tumor tissues using a terminal deoxynucleotidyl transferase
      dUTP nick end labeling (TUNEL) assay. Results: The triple-regulated CRAd carrying
      SG611-PDCD5 and nude mouse xenograft models of K562 cells were successfully
      constructed. In vitro treatment with SG611-PDCD5 in combination with low-dose
      daunorubicin elicited more potent anti-proliferative and proapoptotic effects in
      leukemic cells in a dose-dependent manner. The Chou-Talalay analysis revealed
      synergistic anti-proliferative effects in all of the above cell lines. In the
      nude mice xenograft model, the tumor size in the control, daunorubicin, SG611
      PDCD5, and combined treatment groups on day 10 were 170.1+/-47.8, 111.9+/-81.1,
      60.7+/-12.3, and 33.2+/-17.5 mm3, respectively (all P<0.05). The results of the
      TUNEL assay showed significantly more apoptotic cells in the SG611-PDCD5 plus
      daunorubicin group than in the SG611-PDCD5 or daunorubicin groups alone (25+/
      0.82, 12.5+/-2.27, and 7.8+/-2.67 apoptotic cells/field, respectively) (P<0.05).
      Conclusion: The findings suggest that combined treatment with SG611-PDCD5 and
      daunorubicin may be a promising strategy for enhancing chemosensitivity and thus
      lowering the dose-related toxicity of daunorubicin in leukemia therapy.

PMID- 30197524
TI  - Carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa:
      characterization of carbapenemase genes and E-test evaluation of colistin-based
      combinations.
AB  - Background: Carbapenamase producing Acinetobacter baumannii and Pseudomonas
      aeruginosa are emerging worldwide limiting the use of carbapenems as effective
      and safe drugs. Purpose: To characterize different carbapenemase genes carried by
      carbapenem-resistant (CR) A. baumannii and P. aeruginosa isolates and to evaluate
      the in vitro effect of some colistin-based combinations by E-test method in
      Zagazig University Hospitals ICU isolates. Methods: CR A. baumannii and P.
      aeruginosa isolated from the surgical intensive care unit (ICU) were tested for
      carbapenemase genes by polymerase chain reaction and the effect of
      colistin/meropenem and colistin/tigecycline combinations was evaluated by E-test.
      Results: Genes coding for OXA-23, NDM and GES were detected in 90, 66.7 and 50%
      of CR A. baumannii, respectively, while genes coding for VIM, GES, NDM and IMP
      were detected in 50, 40.9, 27.3 and 18.2% of CR P. aeruginosa, respectively.
      Colistin/tigecycline combination showed synergistic and additive effect in 20%
      and 60% of A. baumannii isolates, respectively, while colistin/meropenem
      combination showed synergistic and additive effect in 63.6% and 36.4% of P.
      aeruginosa, respectively. Conclusion: Carbapenemase genes carriage accounts for
      high level carbapenem resistance in our isolates. Colistin/tigecycline and
      colistin/meropenem combinations can be considered for treatment of severe
      infections by CR A. baumannii and P. aeruginosa, respectively.

PMID- 30197525
TI  - Application of tuf gene sequence analysis for the identification of species of
      coagulase-negative staphylococci in clinical samples and evaluation of their
      antimicrobial resistance pattern.
AB  - Introduction: Coagulase-negative staphylococci (CoNS) are normal inhabitants of
      human skin and mucous membranes. However, CoNS represent one of the major
      nosocomial pathogens, especially in immunocompromised patients. The increasing
      incidence of CoNS and mainly methicillin-resistant strains underlines the need
      for an accurate identification of Staphylococcus isolates at the species level.
      Analysis of the tuf gene proved to be an accurate tool for the species
      identification of CoNS. The aims of this study were to identify the CoNS species
      by tuf gene-based polymerase chain reaction method and sequencing, and to
      determine the frequency of CoNS clinical isolates resistant to methicillin
      (MRCoNS) and other antibiotics. Methods: A total of 200 staphylococci isolates
      were collected from various clinical samples. Phenotyping methods were used for
      initial identification followed by polymerase chain reaction amplification of tuf
      gene with subsequent sequencing. The phylogenetic relationships among species
      were analyzed using the neighbor-joining method based on the partial gene
      sequence of tuf. Microbroth dilution test was used for screening methicillin
      resistance, and disk diffusion susceptibility testing was performed for
      evaluation of antibiotic resistance among the isolates. Results: In the present
      study, 125 isolates were identified as CoNS; among them, Staphylococcus
      epidermidis 54(43.2%) and Staphylococcus haemolyticus 50 (40.0%) were
      demonstrated as the most prevalent species. Resistance to methicillin was
      detected in 54.4% of the CoNS based on microbroth dilution method. In disk
      diffusion susceptibility testing, the greatest resistance of CoNS was
      demonstrated for cefoxitin (65.4%), cotrimethoxazole (54.4%), and clindamycin
      (49.6%), while daptomycin (87.2%) and linezolid (83.2%) showed the greatest
      effectiveness for CoNS isolates. Conclusion: Our results confirmed the
      predominance of S. epidermidis and S. haemolyticus among CoNS isolates. The high
      prevalence of MRCoNS strains is a serious concern and strongly suggests the need
      for control program measures in our hospitals in order to reduce MRCoNS
      infections, especially in immunocompromised patients.

PMID- 30197526
TI  - Trough concentration of itraconazole and its relationship with efficacy and
      safety: a systematic review and meta-analysis.
AB  - Objectives: The optimum trough concentration of itraconazole for clinical
      response and safty is controversial. The objective of this systematic review and
      meta-analysis was to determine the optimum trough concentration of itraconazole
      and evaluate its relationship with efficacy and safety. Methods: We searched
      PubMed, EMBASE, Web of Science, the Cochrane Library, Clinical-Trials.gov, and
      three Chinese literature databases (CNKI, WanFang, and CBM). We included
      observational studies that compared clinical outcomes below or above the trough
      concentration cut-off value which we set as 0.25, 0.5, and 1.0 mg/L. The efficacy
      outcomes were rate of successful treatment, rate of prophylaxis failure and
      invasive fungal infection (IFI)-related mortality. The safety outcomes included
      incidents of hepatotoxicity and other adverse events. Results: The study included
      a total of 29 studies involving 2,346 patients. Our meta-analysis showed that
      compared with itraconazole trough concentrations (Ctrough) of >=0.25 mg/L, levels
      of <0.25 mg/L significantly increased the incidence of IFI for prophylaxis (RR
      =3.279, 95% confidence interval [CI] 1.73-6.206). Moreover, the success rate of
      treatment decreased significantly at a cut-off level of 0.5 mg/L (RR =0.396, 95%
      CI 0.176-0.889). An itraconazole trough level of 1.0 mg/L was associated with
      hepatotoxicity and other adverse events in a review of many studies. Conclusion:
      An itraconazole trough concentration of 0.25 mg/L should be considered as the
      lower threshold for prophylaxis, and a target concentration of 0.5 mg/L should be
      the lower limit for effective treatment. A trough level of 1.0 mg/L is associated
      with increased hepatotoxicity and other adverse events (using High Performance
      Liquid Chromatography [HPLC]).

PMID- 30197527
TI  - Phenotypic and molecular characteristics of methicillin-resistant and methicillin
      susceptible Staphylococcus aureus isolated from pigs: implication for livestock
      association markers and vaccine strategies.
AB  - Background: Routine non-therapeutic antimicrobial use and overcrowding in animal
      farming may facilitate the propagation of methicillin-resistant Staphylococcus
      aureus (MRSA). This study aimed to examine the carriage prevalence and phenotype
      genotype characteristics of MRSA and methicillin-susceptible S. aureus isolated
      from pigs. Methods: Nasal swabs were collected from 1,458 pigs in 9 pig farms and
      3 slaughterhouses. All strains were tested for antimicrobial susceptibility,
      resistance genes, and virulence genes, and characterized by multilocus sequence
      typing. The correspondence analysis was conducted to explore the relationships
      between multiple phenotypic and molecular characteristics of S. aureus isolates.
      Results: In the 1,458 pigs, the carriage prevalence was 9.5% for S. aureus, 3.3%
      for MRSA, and 9.3% for multidrug-resistant S. aureus. Notably, 97.1% S. aureus
      isolates were multidrug resistant, and the predominant resistance pattern was non
      susceptible to clindamycin, tetracycline, and erythromycin. The predominant
      genotype was CC9 (ST9) for S. aureus and MRSA isolates. Importantly, all S.
      aureus isolates were negative for the scn gene and resistant to tetracycline.
      Notably, all 9 linezolid-resistant isolates were classified as multidrug
      resistance, including 1 expressing the cfr gene and 6 expressing the optrA gene.
      The correspondence analysis showed a significant relationship between clonal
      complexes and resistance pattern or virulence genes. For example, CC9 was
      associated with extensive drug-resistance and co-carrying chp, sak, and hlb, and
      CC1 was associated with multidrug resistance and co-carrying sak and hlb.
      Conclusion: The significant correspondence relationship between multiple
      characteristics provides some implication for vaccine strategies and new ideas
      for monitoring new epidemiologic clones.

PMID- 30197528
TI  - Obesity in Germany and Italy: prevalence, comorbidities, and associations with
      patient outcomes.
AB  - Purpose: This study investigated the association between body mass index (BMI)
      and three comorbid conditions (type 2 diabetes [T2D], prediabetes, and
      hypertension) on humanistic and economic outcomes. Patients and methods: This
      retrospective observational study collected data from German (n=14286) and
      Italian (n=9433) respondents to the 2013 European Union National Health and
      Wellness Survey, a cross-sectional, nationally representative online survey of
      the general adult population. Respondents were grouped, based on their self
      reported BMI, and stratified into three other comorbid conditions (T2D,
      prediabetes, and hypertension). Generalized linear models, controlling for
      demographics and health characteristics, tested the relationship between BMI and
      health status, work productivity loss, and health care resource utilization.
      Indirect and direct costs were calculated based on overall work productivity loss
      and health care resource utilization, respectively. The same generalized linear
      models were also performed separately for those with T2D, prediabetes, and
      hypertension. Results: The sample of German respondents was 50.16% male, with a
      mean age of 46.68 years (SD =16.05); 35.24% were classified as overweight and
      21.29% were obese. In Italy, the sample was 48.34% male, with a mean age of 49.27
      years (SD =15.75); 34.85% were classified as overweight, and 12.89% were obese.
      Multivariable analyses demonstrated that, in both countries, higher BMI was
      associated with worse humanistic outcomes and only those from Germany also
      reported greater direct and indirect costs. Differences in the impact of BMI on
      outcomes by country were additionally found when the sample was stratified into
      those with prediabetes, T2D, and hypertension. Conclusion: The high percentage of
      patients who are overweight or obese in Germany and Italy remains problematic.
      Better elucidating the impact of overweight or obese BMI, as well as the
      incremental effects of relevant comorbid conditions, on humanistic and economic
      outcomes is critical to quantify the multifaceted burden on individuals and
      society.

PMID- 30197529
TI  - Liver function tests in identifying patients with liver disease.
AB  - Background and aims: Many patients with liver disease come to medical attention
      once they have advanced cirrhosis or acute decompensation. Most often, patients
      are screened for liver disease via liver function tests (LFTs). There is very
      limited published data evaluating laboratory values with biopsy-proven stages of
      hepatic fibrosis. We set out to evaluate whether any correlation exists between
      routine LFTs and stages of hepatic fibrosis. Methods: A large retrospective
      observational study on 771 liver biopsies was conducted for evaluating the stage
      of fibrosis with AST, ALT, INR, BUN, creatinine, platelets, alkaline phosphatase,
      bilirubin, and albumin. Mean and 95% confidence intervals were used to describe
      the distributions of serum markers in different fibrosis stages. Multivariable
      generalized linear models were used and a two-tailed P-value was calculated.
      Results: ALT was not statistically significant for any stage, and AST was
      statistically significant for stage 3 and 4 fibrosis. INR was statistically
      significant only in stage 4 disease but remained near the upper limit of normal
      range. Albumin failed to show a clinically relevant association. Platelets
      remained within normal laboratory range for all stages. The remaining laboratory
      values failed to show statistical and clinical significance. Conclusion: The
      health care burden from chronic liver disease (CLD) will likely continue to rise,
      unless clinicians are made aware that normal or near normal laboratory findings
      may be seen in asymptomatic patients. Earlier identification of asymptomatic
      patients will allow for treatment with new promising modalities and decrease
      morbidity and mortality from CLD. Our study shows that laboratory values
      correlate poorly with liver disease.

PMID- 30197530
TI  - Role of intravenous iron in the treatment of anemia in patients with
      gastrointestinal tract tumors undergoing chemotherapy: a single-center,
      observational study.
AB  - Purpose: The prevalence of anemia ranges between 30% and 90% in cancer patients,
      affecting the health status, quality of life, and treatment outcome. Therefore, a
      proper diagnosis and management of anemia is crucial in these patients. Iron
      deficiency is diagnosed in~32%-60% of the cases. In this observational study, we
      evaluated the efficacy and safety of intravenous iron (ferric carboxymaltose
      [FCM], Ferinject(r)) in the treatment of iron-deficiency anemia in patients with
      gastrointestinal tumors undergoing palliative or adjuvant chemotherapy. Patients
      and methods: Thirty patients with gastrointestinal tumors undergoing chemotherapy
      diagnosed with iron-deficiency anemia were included in the study and received at
      least one FCM administration. The need for iron replacement therapy was evaluated
      by the assessment of hemoglobin and iron status parameters, and patients could be
      treated with FCM during 12-14 weeks. Paired t-test approach was used to evaluate
      the mean differences between the baseline and the end of the study. A p-value of
      <0.05 was considered statistically significant. Results: Data showed that there
      was a statistically significant increase in the mean of hemoglobin (10.3 vs 11.2
      g/dL), ferritin (230.3 vs 877.0 ng/mL), transferrin saturation (13.0% vs 19.7%),
      and serum iron (42.3 vs 59.6 mg/mL) from the baseline to the end of the study in
      cancer patients. Most of the patients (n=25) were only administered one dose of
      FCM. There was one FCM-related adverse event during the study. Conclusion: FCM
      was well tolerated and had a positive impact in the treatment of iron-deficiency
      anemia in patients with gastrointestinal tract tumors undergoing chemotherapy.

PMID- 30197531
TI  - Acromegaly: a challenging condition to diagnose.
AB  - Acromegaly is an uncommon, chronic disease, characterized by hypersecretion of a
      pituitary growth hormone by somatotroph adenomas, along with increased levels of
      insulin-like growth factor-1. Although acromegaly presents a wide array of
      clinical manifestations, the salient symptoms include acral and soft tissue
      enlargement, joint pain, heart and respiratory failure, diabetes mellitus, and
      hypertension, leading to increased morbidity and mortality. Hence, early
      diagnosis of the disease is critical to enhance life expectancy and quality of
      life. New approaches are being developed for diagnosis and surveillance (both
      screening and follow-up), including sensitive biochemical assays and the use of
      MRI to visualize extremely small tumors, and are helpful in the early diagnosis
      of acromegaly, subsequent treatment, and disease control. This mini-review
      summarizes the most common and effective tools used in the diagnosis of
      acromegaly.

PMID- 30197533
TI  - OnabotulinumtoxinA injections for atypical odontalgia: an open-label study on
      nine patients.
AB  - Background: Atypical odontalgia (AO) manifests as continuous pain in the region
      of one or several teeth, in the absence of signs of dental pathology. Currently,
      there is insufficient evidence to establish treatment guidelines for AO. The aim
      of this study was to describe the effectiveness and safety of treatment with
      OnabotulinumtoxinA (OnabotA) on a series of patients with AO. Methods: Nine
      patients with AO (four males and five females, aged between 31 and 77 years)
      received injections of OnabotA in the region of pain. The dosage used in each
      procedure ranged between 10 and 30 U, spread between 4 and 12 injection sites
      along the gums (n=9), the lips (n=3), and the hard palate (n=1). The median
      follow-up time was 27 months (interquartile range, IQR 20-40) and the median
      number of injection sessions per patient was seven (IQR 4.5-9). The assessment
      variables included the change in the maximal intensity of pain on a 0-10
      numerical rating scale (NRS), the response latency, and the duration of the
      effect. Results: All patients experienced a significant improvement, with >=50%
      of reduction in the intensity of the maximal pain. The median of reduction of
      maximal pain after treatment was six points on the NRS (IQR 5-8.5). The response
      latency was 2-15 days and the duration of the effect was 2-6 months. No
      significant adverse reactions were registered. Conclusion: OnabotA may be a safe
      and effective option for the treatment of AO.

PMID- 30197532
TI  - Paravertebral blocks and enhanced recovery after surgery protocols in breast
      reconstructive surgery: patient selection and perspectives.
AB  - The management of postoperative pain is of critical importance for women
      undergoing breast reconstruction after surgical treatment for breast cancer.
      Mitigating postoperative pain can improve health-related quality of life, reduce
      health care resource utilization and costs, and minimize perioperative opiate
      use. Multimodal analgesia pain management strategies with nonopioid analgesics
      have improved the value of surgical care in patients undergoing various
      operations but have only recently been reported in reconstructive breast surgery.
      Regional anesthesia techniques, with paravertebral blocks (PVBs) and transversus
      abdominis plane (TAP) blocks, and enhanced recovery after surgery (ERAS) pathways
      have been increasingly utilized in opioid-sparing multimodal analgesia protocols
      for women undergoing breast reconstruction. The objectives of this review are to
      1) comprehensively review regional anesthesia techniques in breast
      reconstruction, 2) outline important components of ERAS protocols in breast
      reconstruction, and 3) provide evidence-based recommendations regarding each
      intervention included in these protocols. The authors searched across six
      databases to identify relevant articles. For each perioperative intervention
      included in the ERAS protocols, the literature was exhaustively reviewed and
      evidence-based recommendations were generated using the Grading of
      Recommendations, Assessment, Development, and Evaluation system methodology. This
      study provides a comprehensive evidence-based review of interventions to optimize
      perioperative care and postoperative pain control in breast reconstruction.
      Incorporating evidence-based interventions into future ERAS protocols is
      essential to ensure high value care in breast reconstruction.

PMID- 30197535
TI  - MicroRNA-200b expression level is negatively associated with pathological grading
      in human gliomas.
AB  - Aim: To elucidate the clinical implication of microRNA (miRNA)-200b in the
      pathological grading of gliomas. Methods: We searched the Chinese National
      Knowledge Infrastructure, Web of Knowledge, Embase, and PubMed databases. Related
      articles were assessed, and ORs with 95% CIs were calculated to examine the
      relationship between miRNA-200b expression levels and the World Health
      Organization (WHO) glioma grade, patients' sex and age, tumor size, and extent of
      surgical resection. Heterogeneity, publication bias, and stability of the pooled
      results of the included studies were also analyzed. MiR-200b expression in 87
      human glioma tissues (50 high grade and 37 low grade) and matched 41 non
      neoplastic brain tissues was measured by real-time quantitative RT-PCR assay.
      Results: Five eligible studies involving 630 patients were included in the
      present meta-analysis. The miRNA-200b expression in glioma tissues was negatively
      associated with the WHO glioma grade (OR, 0.070; 95% CI, 0.007-0.678; P=0.022).
      No significant correlations were found between miRNA-200b and sex (P=0.858), age
      (P=0.776), tumor size (P=0.134), or extent of resection (P=0.778). In our own
      test, compared with non-neoplastic brain tissues, the expression level of miR
      200b was significantly decreased in glioma tissues (tumor vs normal: 4.29+/-1.90
      vs 10.45+/-2.34, P<0.001). In addition, we found that the glioma tissues from
      high-grade tumors (grade III and IV) had much lower miR-200b expression than
      glioma tissues from low grade tumors (grade I and II). Conclusion: Our results
      suggest that the miRNA-200 expression level may be negatively associated with the
      WHO glioma grade (malignancy). MiRNA-200 might serve as a prognostic and
      diagnostic biomarker or a helpful therapeutic target.

PMID- 30197534
TI  - Assessment and pathophysiology of pain in cardiac surgery.
AB  - Analysis of the problem of surgical pain is important in view of the fact that
      the success of surgical treatment depends largely on proper pain management
      during the first few days after a cardiosurgical procedure. Postoperative pain is
      due to intraoperative damage to tissue. It is acute pain of high intensity
      proportional to the type of procedure. The pain is most intense during the first
      24 hours following the surgery and decreases on subsequent days. Its intensity is
      higher in younger subjects than elderly and obese patients, and preoperative
      anxiety is also a factor that increases postoperative pain. Ineffective
      postoperative analgesic therapy may cause several complications that are
      dangerous to a patient. Inappropriate postoperative pain management may result in
      chronic pain, immunosuppression, infections, and less effective wound healing.
      Understanding and better knowledge of physiological disorders and adverse effects
      resulting from surgical trauma, anesthesia, and extracorporeal circulation, as
      well as the development of standards for intensive postoperative care units are
      critical to the improvement of early treatment outcomes and patient comfort.

PMID- 30197536
TI  - Tissue transglutaminase 2 expression is epigenetically regulated in human lung
      cancer cells and prevents reactive oxygen species-induced apoptosis.
AB  - Purpose: Tissue transglutaminase 2 (TG2) is a stress-regulated protein and
      associated with cancer cell survival. However, the effects of TG2 expression in
      human non-small-cell lung cancer (NSCLC) cells on reactive oxygen species (ROS)
      production and redox homeostasis have not been fully elucidated. Materials and
      methods: We investigated the TG2 expression and activity in A549, H1299, H1355,
      and H460 lung cancer cells by Western blots and quantitative polymerase chain
      reaction assay. The enzyme-linked immunosorbent assay was used for
      transglutaminase activity. The epigenetic expression was characterized with
      histone deacetylase inhibitor trichostatin A and DNA methyltransferase inhibitor
      5-Aza treatment. TG2 expression was inhibited by siRNA transfection and the
      intracellular calcium was measured by Flow-3AM assay, apoptosis was analyzed by
      Annexin V/propidium iodide assay, and intracellular ROS was detected by
      fluorescence-activated cell sorting analysis. The ROS scavenger N-acetyl-L
      cysteine (NAC) was applied to reduce TG2-knockdown-induced oxidative stress.
      Results: Only A549 cells expressing high levels of TG2 correlated with high TG2
      activity. The expression of TG2 can be regulated by epigenetic regulation in
      A549, H1299, and H1355 cells. The data also show that TG2 reduction induces
      apoptosis in A549 and H1299 cells. Furthermore, increased intracellular ROS and
      calcium levels were both detected in TG2-reduced cells. Moreover, endoplasmic
      reticulum stress inhibitor (salubrinal) and antioxidant NAC were able to reduce
      ROS and calcium levels to recover cell viability. Interestingly, the extrinsic
      and intrinsic apoptosis pathways were activated with a p53 independence upon TG2
      reduction. TG2 reduction not only attenuated AKT activation but also reduced
      superoxide dismutase 2 (SOD2) expression. Exogenous NAC partially recovered SOD2
      expression, indicating that mitochondrial-mediated apoptosis accounts for a part
      of but not all of the TG2-reduction-related death. Conclusion: TG2 plays a
      protection role in NSCLC cell lines. Regardless of the endogenous level of TG2
      and p53 status, reduction of TG2 may result in oxidative stress that induces apop
      tosis. Therefore, target TG2 expression represents a logical strategy for NSCLC
      management.

PMID- 30197537
TI  - Gfi-1 promotes proliferation of human cervical carcinoma via targeting of FBW7
      ubiquitin ligase expression.
AB  - Background: The independent growth factor 1 (Gfi-1) is a transcription factor
      essential for several diverse hematopoietic functions and developments. However,
      the role and molecular mechanism of Gfi-1 in the development and progression of
      cervical cancer remains unclear. Purpose: The present study investigates the
      relation of expression of Gfi-1 with prognoses in patients with cervical cancer.
      Methods: We used Western blot and reverse transcription polymerase chain reaction
      (RT-PCR) and the inhibition of proliferation and metastasis of cervical cancer
      cells in vitro. Results: This study confirms that the expression of Gfi-1 in
      cervical cancer tissues was higher than that in adjacent normal tissues. The
      level of Gfi-1 mRNA in human cervical cancer tissues was significantly higher
      than that in normal tissues adjacent to cancer. Furthermore, overexpression of
      Gfi-1 promoted cell proliferation, colony formation, and migration of cervical
      cancer cells. The increased expression of Gfi-1 promotes the proliferation of
      cervical cancer cells targeting the tumor suppressor F-box and WD repeat domain
      containing 7 (FBW7). Clinically, our data suggest that overexpression of Gfi-1 is
      associated with poor prognosis in patients with cervical cancer. In a tumor
      xenograft model, knockdown of Gfi-1 inhibited the tumor growth of Hela cells in
      vivo. Conclusion: Our results reveal that Gfi-1 plays an important role in
      cervical cancer and Gfi-1/FBW7 axis serves as a potential therapeutic target for
      cervical cancer.

PMID- 30197538
TI  - Using LC-MS/MS-based targeted proteomics to monitor the pattern of ABC
      transporters expression in the development of drug resistance.
AB  - Purpose: The overexpression of ATP-binding cassette transporters (ABC
      transporters), mainly including permeability glycoproteins (P-gp), multidrug
      resistance (MDR)-related protein 1 (MRP1), and breast cancer resistance proteins
      (BCRP), is one of the main reasons for the development of MDR which directly
      leads to chemotherapy failure. However, most of the currently used detection
      methods in MDR-related studies are qualitative or semiquantitative, but not
      quantitative. As a result, the measurement criteria of different experiments are
      not unified. Moreover, there are many contradictory results of the studies of the
      induction effect of drugs on ABC transporters. So, it is necessary to establish a
      quantitative assay for the quantification of P-gp, MRP1, and BCRP to study the
      mechanism of drug resistance. Methods: In this paper, a novel and advanced liquid
      chromatography/mass spectrometry (MS)/MS-based targeted proteomics method for the
      quantification of P-gp, MRP1, and BCRP was developed and validated. Then, the
      cell lines MCF-7, HepG-2, and SMMC-7721 were, respectively, induced by different
      concentrations of doxorubicin (adriamycin [ADM]), mitoxantrone (MX), and
      methotrexate (MTX), to establish resistance cell lines. The method established
      was used to quantify the expression of P-gp, MRP1, and BCRP. Results: The result
      showed that the induction effects of drugs on protein were relatively stable and
      selective. ADM, MX, and MTX could induce overexpression of P-gp, MRP1, and BCRP.
      And, the induction effect of different drugs on proteins was selective. The
      pattern of overexpression of ABC transporters in the three types of resistance
      cell lines was different. Conclusion: During the development of drug resistance,
      the cell type and patch, but not drug type, were the most important determinant
      factors of the overexpression level of ABC transporters in resistance cell lines.
      This study provides a good foundation for understanding the development of drug
      resistance in cell lines and can be used to explain the contradictory results in
      other published studies as described above.

PMID- 30197539
TI  - Early treatment with talk therapy or antidepressants in severely bereaved people
      and risk of suicidal behavior and psychiatric illness: an instrumental variable
      analysis.
AB  - Purpose: Losing a loved one to death is a common and natural life-course
      experience. Still, bereavement has been associated with an increased risk of
      suicidal behavior and psychiatric hospitalization and little is known of how to
      counter these adverse events. We aimed to study the effect of early treatment in
      primary care with talk therapy (TT) or antidepressants (AD) in severely bereaved
      people. Methods: We conducted a population-based cohort study including 207,435
      adult Danes who experienced a severe loss in 1996-2013. We compared treatment and
      no treatment with either of the two treatment regimens within 6 months after the
      loss. The main outcome was a serious mental health condition (defined as suicide,
      deliberate self-harm, or psychiatric hospitalization) occurring >6 months after
      bereavement. Adjusted risk differences (RDs) 2 years after bereavement were
      calculated using both standard regression analysis and instrumental variable
      analysis (IVA) in which estimated physician preferences for treatment served as
      instruments. Results: The standard adjusted regression analysis showed a higher
      risk of developing a serious mental health condition associated with both TT (RD,
      7.1; 95% CI, 5.0 to 9.1 per 1000 people) and AD (RD, 30.1; 95% CI, 25.7 to 34.6
      per 1000 people). The IVA, which was used to control for unmeasured confounding,
      showed that TT was associated with a lower risk of a serious mental health
      condition (RD, -17.1; 95% CI, -30.7 to -3.5 per 1000 people), whereas the results
      were inconclusive for AD (RD, -8.6; 95% CI, -62.6 to 45.4 per 1000 people).
      Conclusion: This study suggests that early treatment with TT is associated with
      reduced long-term risk of serious mental health conditions in severely bereaved
      people. No clear benefit or harm of treatment with AD after bereavement was
      ascertained since the statistical precision was low.

PMID- 30197541
TI  - Optimal timing of complete revascularization in patients with ST-segment
      elevation myocardial infarction and multivessel disease: a pairwise and network
      meta-analysis.
AB  - Introduction: The optimal revascularization strategy for patients with ST-segment
      elevation myocardial infarction and multivessel disease is unclear. In this
      study, we performed a meta-analysis to determine the optimal revascularization
      strategy for treating these patients. Methods: Searches of PubMed, the Cochrane
      Library, clinicaltrial.gov, and the reference lists of relevant papers were
      performed covering the period between the year 2000 and March 20, 2017. A
      pairwise analysis and a Bayesian network meta-analysis were performed to compare
      the effectiveness of early complete revascularization (CR) during the index
      hospitalization, delayed CR, and culprit only revascularization (COR). The
      primary endpoint was the incidence of major adverse cardiac events (MACE), which
      were defined as the composite of recurrent myocardial infarction (MI), repeat
      revascularization, and all-cause mortality. The secondary endpoints were the
      rates of all-cause mortality, recurrent MI, and repeat revascularization. This
      study is registered at PROSPERO under registration number CRD42017059980.
      Results: Eleven randomized controlled trials including a total of 3,170 patients
      were identified. A pairwise meta-analysis showed that compared with COR, early CR
      was associated with significantly decreased risks of MACE (relative risk [RR]
      0.47, 95% CI 0.39-0.56), MI (RR 0.55, 95% CI 0.37-0.83), and repeat
      revascularization (RR 0.35, 95% CI 0.27-0.46) but not of all-cause mortality (RR
      0.78, 95% CI 0.52-1.16). These results were confirmed by trial sequential
      analysis. The network meta-analysis showed that early CR had the highest
      probability of being the first treatment option during MACE (89.2%), MI (83.3%),
      and repeat revascularization (80.4%). Conclusion: Early CR during the index
      hospitalization was markedly superior to COR with respect to reducing the risk of
      MACE, as CR significantly decreased the risks of MI and repeat revascularization
      compared with COR. However, further study is warranted to determine whether CR
      during the index hospitalization can improve survival in patients with concurrent
      ST-segment elevation myocardial infarction and multivessel disease. The optimal
      timing of CR remains inconclusive considering the small number of studies and
      patients included in the analysis comparing early and delayed CR.

PMID- 30197540
TI  - HPV self-sampling in cervical cancer screening: the effect of different
      invitation strategies in various socioeconomic groups - a randomized controlled
      trial.
AB  - Background: Participation in cervical cancer screening varies by socioeconomic
      status. The aims were to assess if offering human papilloma virus (HPV) self
      sampling kits has an effect on screening participation among various
      socioeconomic groups and to determine if two invitation strategies for offering
      self-sampling influence the participation rate equally. Methods: The study was
      based on registry data that were applied to data from a randomized controlled
      trial (n=9,791) measuring how offering HPV self-sampling affected screening
      participation. The women received either 1) a self-sampling kit mailed directly
      to their homes (directly mailed group); 2) an invitation to order the kit (opt-in
      group); or 3) a standard second reminder to attend regular cytology screening
      (control group). The participation data were linked to registries containing
      socioeconomic information. Results: Women in the directly mailed group
      participated significantly more than women in the control group, regardless of
      their socioeconomic status, but the largest effects were observed in Western
      immigrants (participation difference [PD]=18.1%, 95% CI=10.2%-26.0%) and social
      welfare recipients (PD=15.2%, 95% CI=9.7%-20.6%). Compared with the control
      group, opt-in self-sampling only had an insignificant effect on participation
      among women who were immigrants, retired, or less educated. Western immigrants
      had a significantly higher increase in participation than native Danish women
      when kits were mailed directly compared with the opt-in strategy (PD=18.1%, 95%
      CI=10.2%-26.2% and PD=5.5%, 95% CI=2.9%-8.1%, respectively, P=0.01). Conclusion:
      All socioeconomic groups benefited from the directly mailed strategy in terms of
      higher screening participation, but Western immigrants and lower socioeconomic
      groups seemed to benefit the most. Immigrants and some lower socioeconomic groups
      only had insignificant benefits of opt-in self-sampling. The directly mailed
      strategy might be preferable to opt-in self-sampling because it ensures that
      ethnic minority groups obtain benefits of introducing HPV self-sampling in an
      organized cervical cancer screening program. Trial registration: Current
      Controlled Trials NCT02680262. Registered February 10, 2016.

PMID- 30197542
TI  - Pelvic floor disorders in postpartum adolescents in the Western Amazon: a cross
      sectional study.
AB  - Purpose: To analyze the postpartum pelvic floor disorders (PFD) and mode of
      delivery among adolescents, late adolescents, and young women from Western
      Amazon. Patients and methods: Cross-sectional study was carried out in the urban
      area of Western Amazon in the city of Rio Branco, Acre, Brazil, from October 2016
      to February 2017. This is a convenience sample of women up to 30 years who
      completed six months postpartum, separated in three groups according to maternal
      age: adolescents (age <=19 years), late adolescents (20-24 years), and young
      women (25-30 years). Participants were home interviewed and answered Pelvic Floor
      Distress Inventory-20 (PFDI-20). Delivery clinical data were collected from
      patient's medical records. Results: In total, 285 participants were interviewed:
      41 adolescents, 103 late adolescents, and 141 young women. After controlling for
      confounding factors, prevalences of PFD were higher in the adolescents' group
      compared with the young women's group (urinary incontinence [UI], prevalence
      ratio [PR] = 1.75, 95% CI 1.14-2.69; urge urinary incontinence [UUI], PR = 1.88,
      95% CI 1.02-3.47; stress urinary incontinence, PR = 2.00, 95% CI 1.11-3.62; fecal
      incontinence [FI], PR = 4.40, 95% CI 1.36-14.27). PFDI-20 scores also presented
      higher values in the adolescent group (Pelvic Organ Prolapse Distress Inventory
      [POPDI], PR = 2.02, 95% CI 1.49-2.75; urinary distress inventory [UDI], PR =
      2.09, 95% CI 1.47-2.98; PFDI, PR = 2.12, 95% CI 1.47-2.98). Analyzing the
      influence of cesarean section, adolescents have higher prevalence of UI (PR =
      1.84, 95% CI 1.04-3.26, P=0.037), UUI (PR = 2.36, 95% CI 1.03-5.40, P=0.042), and
      FI (PR = 4.09, 95% CI 1.21-13.81, P=0.023). In addition, POPDI (PR = 2.15, 95% CI
      1.60-2.89, P<0.001), UDI (PR = 2.25, 95% CI 1.61-3.16, P<0.001), and PFDI (PR =
      2.27, 95% CI 1.68-3.08, P<0.001) scores are also higher among adolescents where
      the baby is born by cesarean section. Conclusion: Adolescents present higher
      prevalence and symptoms of PFD; furthermore, cesarean delivery has a greater
      negative influence on the pelvic floor of adolescents when compared with young
      women. This reinforces the importance of PFD investigation among the adolescent
      population, mainly in developing countries which have high rates of adolescent
      pregnancy and cesarean section.

PMID- 30197543
TI  - Uterine flexion suture: modified B-Lynch uterine compression suture for the
      treatment of uterine atony during cesarean section.
AB  - Objective: The aim of this study was to report our clinical experience of
      applying a uterine flexion suture, which was modified from the B-Lynch uterine
      compression suture, for treating uterine atony during cesarean section. Materials
      and methods: This is a retrospective descriptive study describing the use of a
      new technique, uterine flexion suture, for treating uterine atony during cesarean
      section. The study period was from January 2009 to December 2017 at Udonthani
      Hospital, Udonthani, Thailand. Uterine atony during cesarean section was treated
      by manual compression, intravenous oxytocin, methylergonovine maleate, and
      prostaglandins and then was observed for 10-15 minutes before applying a uterine
      flexion suture in the failed medical treatment cases. The patients were observed
      for vaginal bleeding, hematometra, and infection after operation. Uterine
      ultrasound scan results on days 1, 7, and 30 postoperation were also reviewed.
      Results: Fifty-seven patients with uterine atony during cesarean delivery
      received the uterine flexion suture. The mean age of patients was 27.0 (15-44
      years). Thirty-four patients were primipara. The indications for cesarean section
      were cephalopelvic disproportion in 27 (47.4%) cases, and previous cesarean
      section in 11 (19.3%) cases. Neither postoperative excessive bleeding nor
      hysterectomy was observed. There was no hematometra or serious postoperative
      complication after surgery. The estimated time for uterine flexion suture is only
      2-3 minutes and was very easy to perform. Conclusion: Uterine flexion suture
      technique, which was modified from the B-Lynch suture, was inexpensive, quick,
      and effective in the treatment of atonic postpartum uterus in women undergoing
      cesarean section.

PMID- 30197544
TI  - Stroke prevention in Europe: how are 11 European countries progressing toward the
      European Society of Cardiology (ESC) recommendations?
AB  - Purpose: Stroke is a leading cause of death and disability, although studies show
      that 90% of strokes can be prevented. The evidence base for stroke prevention is
      well established, and this study aimed to investigate how well European countries
      are adopting the European Society of Cardiology (ESC) guidelines, particularly
      toward implementation of the recommended best practice in stroke prevention.
      Materials and methods: We developed a stroke prevention scorecard - populated
      with World Health Organization (WHO) data, secondary research, time-series data,
      and a survey of 550 physicians - to benchmark 11 European countries in the
      context of the ESC guidelines. Results: All countries were found to have policies
      in place to manage general behavioral risk factors of noncommunicable disease
      (NCD), but we found that more needs to be done to address cardiovascular disease 
      specifically, stroke risk factors. Although ten of the countries in this study
      endorse the ESC cardiovascular clinical guidelines, implementation is lacking.
      Eight out of the 11 countries received the lowest score in regard to raising
      awareness around stroke, and 7 countries were found not to have a stroke
      registry. Among physicians surveyed in primary care it was reported that less
      than 30% of patients over 40 years old were screened for blood pressure, whereas
      even fewer were screened for atrial fibrillation; in 10 out of the 11 countries,
      less than 20% of patients over 65 years old were screened for atrial
      fibrillation. Conclusion: Although progress is being made in managing the burden
      of NCDs, our findings reveal opportunities for improvement in the primary
      prevention of stroke. Further developments in strategic planning, raising
      awareness, and monitoring disease are required, as is research on barriers to the
      implementation of best practice screening of blood pressure and atrial
      fibrillation in primary care.

PMID- 30197546
TI  - Comprehensive review of fetal adenocarcinoma of the lung.
AB  - Fetal adenocarcinoma of the lung (FLAC) is a rare tumor. It accounts for ~0.1%
      0.5% of all pulmonary neoplasms. Due to its rarity, much of the world literature
      regarding FLAC comes from case reports and case series. FLAC is an adenocarcinoma
      resembling developing fetal lung in its pseudoglandular stage (8-16 weeks of
      gestation). It is distinguishable from pulmonary blastoma (PB) because it lacks
      the mesenchymal component which is a hallmark finding in PB. Due to differences
      in histopathology and clinical course, FLAC has been further categorized into low
      grade (L-FLAC) and high-grade (H-FLAC) forms. L-FLAC displays low nuclear atypia
      and prominent morule formation and has a pure pattern. H-FLAC typically presents
      with at least 50% fetal morphology, and is often associated with other
      conventional types of lung adenocarcinoma. FLAC expresses neuroendocrine markers
      and thyroid transcription factor 1 in most cases. L-FLAC has an aberrant
      nuclear/cytoplasmic expression of beta-catenin and presents mutations in this
      gene. H-FLAC overexpresses p53. These tumors have a very low frequency of
      mutations in KRAS and EGFR; it is thought that they are different from a
      molecular point of view to conventional lung adenocarcinomas. Approximately 25%
      40% of patients are asymptomatic at presentation; most of them are incidental
      findings on chest radiographs. H-FLAC is more common in elderly male patients,
      with a heavy smoking history. L-FLAC tends to occur in young females. Patients
      with L-FLAC are usually diagnosed with stage I-II disease, while patients with H
      FLAC usually present with a more advanced-stage disease. Poor prognostic factors
      for FLAC are thoracic lymphadenopathy, metastases at diagnosis, and tumor
      recurrence; however, the 10-year survival for FLAC is estimated at 75%.

PMID- 30197547
TI  - 1-, 3-, and 5-year survival among early-stage lung cancer patients treated with
      lobectomy vs SBRT.
AB  - Background: Lobectomy has traditionally been recommended for fit patients
      diagnosed with early-stage non-small-cell lung cancer (NSCLC). Recently, however,
      stereotactic body radiotherapy (SBRT) has been introduced as an alternative
      treatment option. The purpose of this investigation is to compare survival
      outcomes for individuals with stage I/II NSCLC treated with lobectomy vs SBRT.
      Methods: This retrospective study included 191 patients (100 surgery, 91 SBRT)
      identified through the Lung Cancer Evaluation Center, Stony Brook, NY, between
      2008 and 2012. Survival and recurrence rates were compared using Kaplan-Meier
      curves, log-rank tests, and Cox proportional hazard models to adjust for possible
      confounders. A subset of cases was propensity-matched to address potential
      differences in health status between groups. Results: 1-, 3-, and 5-year survival
      outcomes were significantly better among patients undergoing lobectomy vs SBRT.
      Survival rates at 3 years were 92.8% and 59.0% (p<0.001) in the 2 groups,
      respectively. Propensity-matched analyses indicated similar findings. Recurrence
      rates were likewise lower among patients undergoing surgery (7.1% vs 21.0%,
      p<0.01 at 3 years); however, statistical significance was not maintained in the
      propensity-matched analysis. Conclusion: These findings add to a growing evidence
      base supporting the use of lobectomy vs SBRT in the treatment of lung cancer
      among healthy, early-stage NSCLC patients.

PMID- 30197545
TI  - From pillow to podium: a review on understanding sleep for elite athletes.
AB  - Sleep is considered vital to human health and well-being, and is critical to
      physiological and cognitive functioning. Elite athletes experience high training
      and competition demands, and are often exposed to various factors, situations,
      and environments that can cause sleep impairments. Previous research has shown
      that athletes commonly experience sleep loss in the lead up to and following
      competition, which could have significant impacts on their preparation,
      performance, and recovery. In particular, the results from previous research show
      significant reductions in total sleep time (~1:40 h:min) and significant
      increases in sleep latency (~45 minutes) following evening competition. Napping
      is common in both the training and competition setting in athletes; however,
      research on the effect of napping on physiology and performance is limited. In
      contrast, research on strategies and interventions to improve sleep are
      increasing in the athletic population, with sleep hygiene research resulting in
      significant improvements in key sleep indices. This review investigates the
      physiological importance of sleep in athletes, current tools to monitor athletes'
      sleep, the role of sleep for cognitive functioning and athletic performance, the
      prevalence of sleep disturbances and the potential mechanisms causing sleep
      disturbances, the role of napping, and different intervention strategies to
      improve sleep.

PMID- 30197549
TI  - Advancing New Testament interpretation through spatio-temporal analysis:
      Demonstrated by case studies.
AB  - This article explores, via three case studies, how spatio-temporal analysis can
      advance New Testament text interpretation. Acts 2, verse 9 to 11 is the text of
      study. Case study 1 applies network analysis to data representing the Roman road
      network constrained by parameters valid for ancient times. This analysis provided
      new information on the background of people attending a festival in Jerusalem.
      Case study 2 located geographical entities from the text in a cartographic
      visualization and provided supportive information to compare contemporary textual
      resources. For the disciplines of textual and conjectural criticism (case study
      3), spatio-temporal analysis opens a new window to study what would be the most
      probable variant of the original text. The case study puts emendations that have
      been proposed over centuries in a 3D spatial context and provides in this way a
      sophisticated tool to relate different alternative variants of a specific text.
      From the case studies, it can be concluded that spatializing, visualizing, and
      spatially analyzing geographical concepts from the texts in Acts 2 contributes to
      the field of New Testament interpretation. Further work will elaborate on the
      findings.

PMID- 30197548
TI  - Preterm Neurodevelopmental Outcomes Following Orosensory Entrainment
      Intervention.
AB  - Previous research indicates that the NTrainer, a pressurized pacifier programmed
      to produce pulsed pneumotactile stimulation during gavage feeds, has been found
      to facilitate non-nutritive suck development and shorten the length of hospital
      stay when used in the Neonatal Intensive Care Unit (NICU). Four groups of
      children, including infants of diabetic mothers (IDM), healthy controls (HI), and
      those with respiratory distress syndrome (RDS), or chronic lung disease (CLD),
      were randomly assigned to an NTrainer therapy or sham 'control' condition when in
      the NICU. At 30 months of age, 113/223 study participants were assessed using
      standardized language, motor, and cognitive assessments. No significant group
      differences were evident between the NTrainer and sham groups in language, motor,
      or cognitive functioning. The NTrainer did not improve nor adversely impact
      language, cognition, or motor outcomes.

PMID- 30197550
TI  - Age of acquisition and proficiency in a second language independently influence
      the perception of non-native speech.
AB  - Sensorimotor processing in children and higher-cognitive processing in adults
      could determine how non-native phonemes are acquired. This study investigates how
      age-of-acquisition (AOA) and proficiency-level (PL) predict native-like
      perception of statistically dissociated L2 categories, i.e., within-category and
      between-category. In a similarity task, participants rated the level of
      similarity between pairs of English syllables from 1 (similar) to 4 (dissimilar).
      Early L2 acquisition predicts accurate within-categorization and high proficiency
      in late L2 acquisition predicts improved between-categorization. Our results
      suggest that the manner in which bilinguals learn to categorize non-native sounds
      depends on the cognitive processes available at the age of L2 exposure.

PMID- 30197551
TI  - Spirituality and mental health status among Northern Plain tribes.
AB  - Spirituality measures often show positive associations with preferred mental
      health outcomes in the general population; however, research among American
      Indians (AIs) is limited. We examined the relationships of mental health status
      and two measures of spirituality - the Midlife Development Inventory (MIDI) and a
      tribal cultural spirituality measure - in Northern Plains AIs, aged 15-54 (n =
      1636). While the MIDI was unassociated with mental health status, the tribal
      cultural spirituality measure showed a significant relationship with better
      mental health status. Mental health conditions disproportionately affect AIs.
      Understanding protective factors such as cultural spirituality that can mitigate
      mental health disorders is critical to reducing these health disparities.

PMID- 30197552
TI  - A survey of high dimension low sample size asymptotics.
AB  - Peter Hall's work illuminated many aspects of statistical thought, some of which
      are very well known including the bootstrap and smoothing. However, he also
      explored many other lesser known aspects of mathematical statistics. This is a
      survey of one of those areas, initiated by a seminal paper in 2005, on high
      dimension low sample size asymptotics. An interesting characteristic of that
      first paper, and of many of the following papers, is that they contain deep and
      insightful concepts which are frequently surprising and counter-intuitive, yet
      have mathematical underpinnings which tend to be direct and not difficult to
      prove.

PMID- 30197554
TI  - Adaptive flood risk management planning based on a comprehensive flood risk
      conceptualisation.
AB  - Densely populated deltas are so vulnerable to sea level rise and climate change
      that they cannot wait for global mitigation to become effective. The Netherlands
      therefore puts huge efforts in adaptation research and planning for the future,
      for example through the national research programme Knowledge for Climate and the
      Delta Programme for the Twenty-first century. Flood risk is one of the key issues
      addressed in both programmes. Adaptive management planning should rely on a sound
      ex-ante policy analysis which encompasses a future outlook, establishing whether
      a policy transition is required, an assessment of alternative flood risk
      management strategies, and their planning in anticipation without running the
      risk of regret of doing too little too late or too much too early. This
      endeavour, addressed as adaptive delta management, calls for new approaches,
      especially because of uncertainties about long-term future developments. For
      flood risk management, it also entails reconsideration of the underlying
      principles and of the application of portfolios of technical measures versus
      spatial planning and other policy instruments. To this end, we first developed a
      conceptualisation of flood risk which reconciles the different approaches of
      flood defence management practice and spatial planning practice in order to
      bridge the gap between these previously detached fields. Secondly, we looked
      abroad in order to be better able to reflect critically on a possible Dutch bias
      which could have resulted from many centuries of experience of successful
      adaptation to increasing flood risk, but which may no longer be sustainable into
      the future. In this paper, we explain the multiple conceptualisation of flood
      risk and argue that explicitly distinguishing exposure determinants as a new
      concept may help to bridge the gap between engineers and spatial planners,
      wherefore we show how their different conceptualisations influence the framing of
      the adaptation challenge. Also, we identify what the Netherlands may learn from
      neighbouring countries with a different framing of the future flood risk
      challenge.

PMID- 30197555
TI  - Flood risk assessments at different spatial scales.
AB  - Managing flood risk, i.e. both the hazard and the potential consequences, is an
      important aspect of adapting to global change and has gained much traction in
      recent decades. As a result, a priori flood risk assessments have become an
      important part of flood management practices. Many methodologies have been set
      up, ranging from global risk assessments for the world as a whole, to local
      assessments for a particular stretch of a river/coast or small town. Most
      assessment frameworks generally follow a similar approach, but there are also
      notable differences between assessments at different spatial scales. This review
      article examines these differences, for instance those related to the
      methodology, use of assessments and uncertainties. From this review, future
      research needs are identified in order to improve flood risk assessments at
      different scales. At global/continental scale, there is a clear need for
      harmonised information on flood defences to improve assessments. Furthermore,
      inclusions of indirect economic effects at the macro-/meso-scale would give a
      better indication of the total effects of catastrophic flooding. At the meso
      /micro-scale, there is an urgent need to improve our understanding of the effects
      of flooding on critical infrastructures, given their importance to society, the
      economy, emergency management and reconstruction. An overarching theme at all
      scales is the validation of flood risk assessments, which is often limited. More
      detailed post-disaster information would allow for improved calibration,
      validation and thus performance of flood risk models. Lastly, the link between
      spatial scales also deserves attention, for instance up- or downscaling
      methodologies.

PMID- 30197556
TI  - Salt marshes to adapt the flood defences along the Dutch Wadden Sea coast.
AB  - Concern about the effects of climate change have set in motion a search for flood
      protection measures to adapt coastlines to the foreseen accelerated sea level
      rise. In this context, the potential role of salt marshes to adapt the Wadden
      Sea's flood defences was explored in the Netherlands Wadden Region Delta
      Programme. This paper provides an overview of the steps taken by the programme in
      developing a climate change adaptation strategy so that others might learn from
      its experiences. The second aim is to summarize the knowledge generated by the
      programme on the potential role of salt marshes as part of a climate change
      adaption strategy. Explorative modelling results indicate that Wadden Sea salt
      marshes affect wave heights, even under extreme conditions. Therefore, a salt
      marsh zone in front of the Wadden Sea dikes that could keep pace with sea level
      rise may result in a reduced dike reinforcement task. A salt marsh potential map
      gives a rough impression of locations that are potentially interesting for salt
      marsh conservation and development, based on the current situation, on available
      information about abiotic conditions for salt marsh formation and the habitats
      present in the coastal zone. Besides elongated stretches were seminatural salt
      marshes are already present or developing, several stretches along the Dutch
      Wadden Sea coast have favourable abiotic conditions for salt marsh development.
      However, the prospects for integrating salt marshes into flood defences depend
      also on other aspects. Various nature conservation agreements are in effect with
      their associated obligations. Furthermore, the foreseen value of salt marsh
      development compared to traditional reinforcements, in terms of both costs and
      benefits, must be considered.

PMID- 30197557
TI  - An integrated approach to flood risk management and spatial quality for a
      Netherlands' river polder area.

PMID- 30197553
TI  - Metallic Nanoparticles for Cancer Immunotherapy.
AB  - Cancer immunotherapy, or the utilization of the body's immune system to attack
      tumor cells, has gained prominence over the past few decades as a viable cancer
      treatment strategy. Recently approved immunotherapeutics have conferred remission
      upon patients with previously bleak outcomes and have expanded the number of
      tools available to treat cancer. Nanoparticles -including polymeric, liposomal,
      and metallic formulations - naturally traffic to the spleen and lymph organs and
      the relevant immune cells therein, making them good candidates for delivery of
      immunotherapeutic agents. Metallic nanoparticle formulations in particular are
      advantageous because of their potential for dense surface functionalization and
      their capability for optical or heat based therapeutic methods. Many research
      groups have investigated the potential of nanoparticle-mediated delivery
      platforms to improve the efficacy of immunotherapies. Despite the significant
      preclinical successes demonstrated by many of these platforms over the last
      twenty years, few metallic nanoparticles have successfully entered clinical
      trials with none achieving FDA approval for cancer therapy. In this review, we
      will discuss preclinical research and clinical trials involving metallic
      nanoparticles (MNPs) for cancer immunotherapy applications and discuss the
      potential for clinical translation of MNPs.

PMID- 30197559
TI  - Agroecosystem specific climate vulnerability analysis: application of the
      livelihood vulnerability index to a tropical highland region.
AB  - In topographically diverse highland terrain, socio-economic and environmental
      conditions can vary dramatically over relatively short distances. This presents a
      challenge for climate resilient development strategies, as exposure to climate
      variability and change, climate impacts, and adaptive capacity differ between
      communities located within common cultural and administrative units. The
      Livelihood Vulnerability Index (LVI) framed within the United Nations
      Intergovernmental Panel on Climate Change (IPCC) vulnerability framework (LVI
      IPCC) offers a tool to assess climate vulnerability through direct household
      surveys. This makes it particularly appropriate for analyses at sub-community and
      community scales. Here we apply the LVI-IPCC to communities of Choke Mountain,
      located in the Blue Nile Highlands of Ethiopia. Recognizing the physiographic and
      climatic diversity that exists in this mountainous environment, we implement LVI
      IPCC analysis for 793 mixed crop-livestock farming households using the five
      distinct agroecological systems (AES) that compose the populated area of Choke
      Mountain as a framework for analysis. For each AES, an LVI index, adaptive
      capacity metric, and LVI-IPCC vulnerability score was calculated. We found that
      each of these metrics varied systematically across AES. High elevation sloping
      lands and low elevation steep lands exhibited relatively low adaptive capacity
      and high vulnerability while midland AES had higher capacity and lower
      vulnerability. These results suggest that resilience building interventions for
      Choke Mountain ecosystems should be targeted to address the specific
      circumstances of each AES. The approach of applying LVI-IPCC at AES scale could
      be applicable to other climate vulnerable mountainous regions.

PMID- 30197558
TI  - Multi-model comparison of the economic and energy implications for China and
      India in an international climate regime.
AB  - This paper presents a modeling comparison on how stabilization of global climate
      change at about 2  degrees C above the pre-industrial level could affect economic
      and energy systems development in China and India. Seven General Equilibrium
      (CGE) and energy system models on either the global or national scale are soft
      linked and harmonized with respect to population and economic assumptions. We
      simulate a climate regime, based on long-term convergence of per capita carbon
      dioxide (CO2) emissions, starting from the emission pledges presented in the
      Copenhagen Accord to the United Nations Framework Convention on Climate Change
      and allowing full emissions trading between countries. Under the climate regime,
      Indian emission allowances are allowed to grow more than the Chinese allowances,
      due to the per capita convergence rule and the higher population growth in India.
      Economic and energy implications not only differ among the two countries, but
      also across model types. Decreased energy intensity is the most important
      abatement approach in the CGE models, while decreased carbon intensity is most
      important in the energy system models. The reduction in carbon intensity is
      mostly achieved through deployment of carbon capture and storage, renewable
      energy sources and nuclear energy. The economic impacts are generally higher in
      China than in India, due to higher 2010-2050 cumulative abatement in China and
      the fact that India can offset more of its abatement cost though international
      emission trading.

PMID- 30197560
TI  - Economic and environmental effects of unilateral climate actions.
AB  - Unilateral climate policy can be detrimental to global climate protection. Our
      objective is to provide insight into such a policy, to quantify the risk of
      carbon leakage, and to investigate the effects related to potential anti-leakage
      measures. We analyze existing definitions of carbon leakage and propose an
      alternative, rigorous one, which is different in three respects. The definition
      is then tested using computable general equilibrium analysis of the global
      economy and decomposition analysis. We identify a list of parameters that affect
      not only the magnitude but also the sign of the carbon leakage rate. Manipulating
      elasticities of substitution suggests that carbon leakage can be either positive
      or negative. Computable general equilibrium models, which are widely applied,
      including by the European Commission in this area, should be transparent, and
      their assumptions call for careful validation. We find that emission limits are
      properly distributed between sectors covered by the European Union Emissions
      Trading System and other sectors for the first commitment period (ended in 2012)
      but not for the second one (ending in 2020), where the target for the non-trading
      sectors should be reduced relative to the target for the trading sectors in order
      to equlize marginal abatement costs.

PMID- 30197562
TI  - Monetary incentives to avoid deforestation under the Reducing emissions from
      deforestation and degradation (REDD)+ climate change mitigation scheme in
      Tanzania.
AB  - The paper estimates and compares the level of Reducing Emissions from
      Deforestation and Degradation (REDD+) payments required to compensate for the
      opportunity costs (OCs) of stopping the conversion of montane forest and miombo
      woodlands into cropland in two agro-ecological zones in Morogoro Region in
      Tanzania. Data collected from 250 households were used for OC estimation. REDD+
      payment was estimated as the net present value (NPV) of agricultural rent and
      forest rent during land clearing, minus net returns from sustainable wood
      harvest, divided by the corresponding reduction in carbon stock. The median
      compensation required to protect the current carbon stock in the two vegetation
      types ranged from USD 1 tCO2e-1 for the montane forest to USD 39 tCO2e-1 for the
      degraded miombo woodlands, of which up to 70 % and 16 %, respectively, were for
      compensating OCs from forest rent during land clearing. The figures were
      significantly higher when the cost of farmers' own labor was not taken into
      account in NPV calculations. The results also highlighted that incentives in the
      form of sustainable harvests could offset up to 55 % of the total median OC to
      protect the montane forest and up to 45 % to protect the miombo woodlands,
      depending on the wage rates. The findings suggest that given the possible factors
      that can potentially affect estimates of REDD+ payments, avoiding deforestation
      of the montane forest would be feasible under the REDD+ scheme. However,
      implementation of the policy in villages around the miombo area would require
      very high compensation levels.

PMID- 30197561
TI  - Estimating changes in flood risks and benefits of non-structural adaptation
      strategies - a case study from Tyrol, Austria.
AB  - Flood damage has increased significantly and is expected to rise further in many
      parts of the world. For assessing potential changes in flood risk, this paper
      presents an integrated model chain quantifying flood hazards and losses while
      considering climate and land use changes. In the case study region, risk
      estimates for the present and the near future illustrate that changes in flood
      risk by 2030 are relatively low compared to historic periods. While the impact of
      climate change on the flood hazard and risk by 2030 is slight or negligible,
      strong urbanisation associated with economic growth contributes to a remarkable
      increase in flood risk. Therefore, it is recommended to frequently consider land
      use scenarios and economic developments when assessing future flood risks.
      Further, an adapted and sustainable risk management is necessary to encounter
      rising flood losses, in which non-structural measures are becoming more and more
      important. The case study demonstrates that adaptation by non-structural measures
      such as stricter land use regulations or enhancement of private precaution is
      capable of reducing flood risk by around 30 %. Ignoring flood risks, in contrast,
      always leads to further increasing losses-with our assumptions by 17 %. These
      findings underline that private precaution and land use regulation could be taken
      into account as low cost adaptation strategies to global climate change in many
      flood prone areas. Since such measures reduce flood risk regardless of climate or
      land use changes, they can also be recommended as no-regret measures.

PMID- 30197563
TI  - The 4Cs of adaptation tracking: consistency, comparability, comprehensiveness,
      coherency.
AB  - Adaptation tracking seeks to characterize, monitor, and compare general trends in
      climate change adaptation over time and across nations. Recognized as essential
      for evaluating adaptation progress, there have been few attempts to develop
      systematic approaches for tracking adaptation. This is reflected in polarized
      opinions, contradictory findings, and lack of understanding on the state of
      adaptation globally. In this paper, we outline key methodological considerations
      necessary for adaptation tracking research to produce systematic, rigorous,
      comparable, and usable insights that can capture the current state of adaptation
      globally, provide the basis for characterizing and evaluating adaptations taking
      place, facilitate examination of what conditions explain differences in
      adaptation action across jurisdictions, and can underpin the monitoring of change
      in adaptation over time. Specifically, we argue that approaches to adaptation
      tracking need to (i) utilize a consistent and operational conceptualization of
      adaptation, (ii) focus on comparable units of analysis, (iii) use and develop
      comprehensive datasets on adaptation action, and (iv) be coherent with our
      understanding of what constitutes real adaptation. Collectively, these form the
      4Cs of adaptation tracking (consistency, comparability, comprehensiveness, and
      coherency).

PMID- 30197564
TI  - Collaborative use of geodesign tools to support decision-making on adaptation to
      climate change.
AB  - Spatial planners around the world need to make climate change adaptation plans.
      Climate adaptation planning requires combining spatial information with
      stakeholder values. This study demonstrates the potential of geodesign tools as a
      mean to integrate spatial analysis with stakeholder participation in adaptation
      planning. The tools are interactive and provide dynamic feedback on stakeholder
      objectives in response to the application of spatial measures. Different
      rationalities formed by underlying internalized values influence the reasoning of
      decision-making. Four tools were developed, each tailored to different
      rationalities varying between a collective or individual viewpoint and analytical
      or political arguments. The tools were evaluated in an experiment with four
      groups of participants that were set around an interactive mapping device: the
      touch table. To study how local decision-making on adaptation can be supported,
      this study focuses on a specific case study in the Netherlands. In this case
      study, multiple different stakeholders need to make spatial decisions on land use
      and water management planning in response to climate change. The collaborative
      use of four geodesign tools was evaluated in an interactive experiment. The
      results show that the geodesign tools were able to integrate the engagement of
      stakeholders and assessment of measures. The experiment showed that decision
      making on adaptation to climate change can benefit from the use of geodesign
      tools as long as the tool is carefully matched to the rationality that applies to
      the adaptation issue. Although the tools were tested to support the design of
      adaptation plans in a Dutch setting, the tools could be used for regional
      adaptation planning in other countries such as the development of regional
      adaptation strategies (RAS) as required by the European Union or on a national
      scale to support developing national adaptation plans of action (NAPAs) as
      initiated by the United Nations Framework Convention on Climate Change (UNFCCC)
      for least developed countries.

PMID- 30197565
TI  - Economic analysis of adaptive strategies for flood risk management under climate
      change.
AB  - Climate change requires reconsideration of flood risk management strategies. Cost
      benefit analysis (CBA), an economic decision-support tool, has been widely
      applied to assess these strategies. This paper aims to describe and discuss
      probabilistic extensions of CBA to identify welfare-maximising flood risk
      management strategies under climate change. First, uncertainty about the changes
      in return periods of hydro-meteorological extremes is introduced by probability
      weighted climate scenarios. Second, the analysis is extended by learning about
      climate change impacts. Learning occurs upon the probabilistic arrival of
      information. We distinguish between learning from scientific progress, from
      statistical evidence and from flood disasters. These probabilistic extensions can
      be used to analyse and compare the economic efficiency and flexibility of flood
      risk management strategies under climate change. We offer a critical discussion
      of the scope of such extensions and options for increasing flexibility. We find
      that uncertainty reduction from scientific progress may reduce initial
      investments, while other types of learning may increase initial investments. This
      requires analysing effects of different types of learning. We also find that
      probabilistic information about climate change impacts and learning is imprecise.
      We conclude that risk-based CBA with learning improves the flexibility of flood
      risk management strategies under climate change. However, CBA provides subjective
      estimates of expected outcomes and reflects different decision-maker preferences
      than those captured in robustness analyses. We therefore advocate robustness
      analysis in addition to, or combined with, cost-benefit analysis to support local
      investment decisions on flood risk reduction and global strategies on allocation
      of adaptation funds for flood risk management.

PMID- 30197566
TI  - Assessing potential future urban heat island patterns following climate
      scenarios, socio-economic developments and spatial planning strategies.
AB  - Climate change and urban development will exacerbate current urban heat island
      effects. While most studies acknowledge the importance of projected temperature
      increases for raising urban temperatures, little attention is paid to the impacts
      of future changes in urbanisation patterns. Yet, steering urban development may
      be an effective strategy to further limit increases in the intensity and
      spreading of the urban heat island effect. We describe a method that allows
      exploring the impact of urban development scenarios on the urban heat island
      effect. This paper starts with a basic analysis of the strength of this effect in
      a temperate climate under relatively favourable conditions based on data from
      amateur weather stations and own observations. It explains local variation in
      observed temperatures and quantifies how the urban heat island effect may develop
      in the coming 30 years. Using the obtained relations, we assess potential future
      changes building on existing scenarios of climatic and socio-economic changes and
      a land use simulation model. Our measurements for the Amsterdam region in the
      Netherlands indicate that the urban heat island effect induces maximum
      temperature differences with the surrounding countryside of over 3  degrees C on
      moderately warm summer days. The simulations of potential future changes indicate
      that strong local temperature increases are likely due to urban development.
      Climate change will, on average, have a limited impact on these changes. Large
      impacts can, however, be expected from the combination of urban development and
      potentially more frequent occurrences of extreme climatic events such as heat
      waves. Spatial planning strategies that reduce the lateral spread of urban
      development will thus greatly help to limit a further increase in urban heat
      island values.

PMID- 30197567
TI  - An interactive simulation and visualization tool for flood analysis usable for
      practitioners.
AB  - Developing strategies to mitigate or to adapt to the threats of floods is an
      important topic in the context of climate changes. Many of the world's cities are
      endangered due to rising ocean levels and changing precipitation patterns. It is
      therefore crucial to develop analytical tools that allow us to evaluate the
      threats of floods and to investigate the influence of mitigation and adaptation
      measures, such as stronger dikes, adaptive spatial planning, and flood disaster
      plans. Up until the present, analytical tools have only been accessible to domain
      experts, as the involved simulation processes are complex and rely on
      computational and data-intensive models. Outputs of these analytical tools are
      presented to practitioners (i.e., policy analysts and political decision-makers)
      on maps or in graphical user interfaces. In practice, this output is only used in
      limited measure because practitioners often have different information
      requirements or do not trust the direct outcome. Nonetheless, literature
      indicates that a closer collaboration between domain experts and practitioners
      can ensure that the information requirements of practitioners are better aligned
      with the opportunities and limitations of analytical tools. The objective of our
      work is to present a step forward in the effort to make analytical tools in flood
      management accessible for practitioners to support this collaboration between
      domain experts and practitioners. Our system allows the user to interactively
      control the simulation process (addition of water sources or influence of
      rainfall), while a realistic visualization allows the user to mentally map the
      results onto the real world. We have developed several novel algorithms to
      present and interact with flood data. We explain the technologies, discuss their
      necessity alongside test cases, and introduce a user study to analyze the
      reactions of practitioners to our system. We conclude that, despite the
      complexity of flood simulation models and the size of the involved data sets, our
      system is accessible for practitioners of flood management so that they can carry
      out flood simulations together with domain experts in interactive work sessions.
      Therefore, this work has the potential to significantly change the decision
      making process and may become an important asset in choosing sustainable flood
      mitigations and adaptation strategies.

PMID- 30197568
TI  - The potential of water markets to allocate water between industry, agriculture,
      and public water utilities as an adaptation mechanism to climate change.
AB  - One of the climate change scenarios that have been developed for the Netherlands
      predicts hotter and drier summers and a substantial drop in river discharge. This
      might lead to water scarcity with detrimental economic and environmental effects.
      Among the possible adaptation responses to climate change-induced water scarcity,
      the re-allocation of water resources among competing uses should also be
      considered. In this paper, we extend and apply a computable general equilibrium
      (CGE) model to assess the potential of water markets (water allocation according
      to its shadow price) to guide the allocation of scarce water across agriculture,
      manufacturing, and public water supply. We develop four scenarios in which the
      scope of water markets is increased from industry-specific to economy-wide. The
      results show that the agricultural sector bears nearly all of the losses from a
      new water-scarce climate, while the manufacturing sectors are able to mitigate
      their losses to a large extent by technical measures. Extending the scope of
      water markets unambiguously increases economic output and results in a re
      allocation of water to the manufacturing sector from the agricultural sector and
      from public water services. If, perhaps for political reasons, public water
      services are excluded from water trading, water is re-allocated from agriculture
      to manufacturing. Depending on which sectors are included, the construction of a
      water market can have negative or positive effects on a sector's output, and
      although the implementation of water markets may be positive for overall economic
      output and can hence assist adaptation, the effect on vulnerable or societally
      sensitive economic sectors, such as public water, should be taken into account
      when implementing such a market.

PMID- 30197569
TI  - Effect of fiber-matrix adhesion on the creep behavior of CF/PPS composites:
      temperature and physical aging characterization.
AB  - The influence of fiber-matrix adhesion on the linear viscoelastic creep behavior
      of 'as received' and 'surface modified' carbon fibers (AR-CF and SM-CF,
      respectively) reinforced polyphenylene sulfide (PPS) composite materials was
      investigated. Short-term tensile creep tests were performed on +/-45 degrees 
      specimens under six different isothermal conditions, 40, 50, 60, 65, 70 and 75 
      degrees C. Physical aging effects were evaluated on both systems using the short
      term test method established by Struik. The results showed that the shapes of the
      curves were affected neither by physical aging nor by the test temperature,
      allowing then superposition to be made. A unified model was proposed with a
      single physical aging and temperature-dependent shift factor, aT,te . It was
      suggested that the surface treatment carried out in SM-CF/PPS had two major
      effects on the creep response of CF/PPS composites at a reference temperature of
      40  degrees C: a lowering of the initial compliance of about 25 % and a slowing
      down of the creep response of about 1.1 decade.

PMID- 30197570
TI  - Infrared divergences and quantum coherence.
AB  - In theories with long-range forces like QED or perturbative gravity, only rates
      that include emitted soft radiation are non-vanishing. Independently of detector
      resolution, finite observables can only be obtained after integrating over the IR
      component of this radiation. This integration can lead to some loss of quantum
      coherence. In this note, however, we argue that it should in general not lead to
      full decoherence. Based on unitarity, we suggest a way to define non-vanishing
      off-diagonal pieces of the IR-finite density matrix. For this IR-finite density
      matrix, we estimate the dependence of the loss of quantum coherence, i.e. of its
      purity, on the scattering kinematics.

PMID- 30197571
TI  - Charged hadron fragmentation functions from collider data: NNPDF Collaboration.
AB  - We present NNFF1.1h, a new determination of unidentified charged-hadron
      fragmentation functions (FFs) and their uncertainties. Experimental measurements
      of transverse-momentum distributions for charged-hadron production in proton
      (anti)proton collisions at the Tevatron and at the LHC are used to constrain a
      set of FFs originally determined from electron-positron annihilation data. Our
      analysis is performed at next-to-leading order in perturbative quantum
      chromodynamics. We find that the hadron-collider data is consistent with the
      electron-positron data and that it significantly constrains the gluon FF. We
      verify the reliability of our results upon our choice of the kinematic cut in the
      hadron transverse momentum applied to the hadron-collider data and their
      consistency with NNFF1.0, our previous determination of the FFs of charged pions,
      kaons, and protons/antiprotons.

PMID- 30197572
TI  - Higgs alignment from extended supersymmetry.
AB  - We consider the effective type-II two-Higgs doublet model originating from Dirac
      gaugino models with extended supersymmetry in the gauge sector, which is
      automatically aligned in the simplest realisations. We show that raising the
      scale at which the extended supersymmetry is manifest and including quantum
      corrections actually improves the alignment. Using an effective field theory
      approach including new threshold corrections and two-loop RGEs, plus two-loop
      corrections to the Higgs mass in the low-energy theory, we study the implications
      from the Higgs mass and other experimental constraints on the scale of
      superpartners. We contrast the results of the minimal Dirac gaugino model, where
      alignment is automatic, with the hMSSM and the MRSSM, where it is not, also
      providing an hMSSM-inspired analysis for the new models.

PMID- 30197573
TI  - Umbilical cord blood banking and its interruptions: notes from Chennai, India.
AB  - What is the relationship between globalization and the body? In both scholarly
      discourse and everyday practice, the relationship between globalization and the
      body has been understood through the idea of accumulation - the intensified and
      interlinked pursuit of health and wealth. Through an examination of private
      umbilical cord blood banking in south India, this paper investigates the
      interplay of accumulation and its interruption in Indians' uptake of this
      practice. Although Chennai-based bankers, doctors and parents explain the recent
      surge in popularity for cord blood banking in the city in terms of interlinked
      financial and familial accumulation, investment and security, Indians' cultural
      and religious conceptions of the latent power of the placenta and cord often work
      against cord blood banking marketers' neat account of twinned economic and
      familial accumulation. Analytic attention to interruption highlights the tensions
      within and precariousness of the accumulation at the heart of the relationship
      between globalization and the body.

PMID- 30197574
TI  - What constitutes 'good practice' in early intervention for psychosis? Analysis of
      clinical guidelines.
AB  - Background: Early Intervention in Psychosis (EIP) services have been implemented
      with the dual aims of preventing harmful outcomes associated with early-onset
      psychosis and improving prognosis. However, concerns have been raised regarding
      the ethical implications of involving young people in EIP services. One way to
      ensure high ethical standards and promote good practice in EIP delivery is
      through governance of clinical practice. This study aimed to investigate the
      normative dimensions of good practice in EIP through examination of clinical
      guideline documents published in England over the past 15 years. Methods: A total
      of 14 clinical guidelines and relevant policy documents for EIP were retrieved
      and analysed using a mixed inductive and deductive thematic approach. Themes were
      derived from the data itself, whereas the development of broader categories was
      performed through a constant comparison with the scientific literature describing
      ethical issues in EIP. Results: Ethical touchpoints of good practice in EIP
      included both procedural and substantive factors, which were seen to be
      interdependent and mutually constitutive. These ethical touchpoints were largely
      implicit in the documents analysed. Procedural requirements of EIP service
      delivery consisted of norms and rules pertaining to EIP service structure,
      adherence to codes of ethics, inclusivity, patient and family centredness and
      appropriate treatment provision. Substantive factors consisted of moral
      attributes that should be cultivated by healthcare professionals working in EIP:
      competency, empathy, sensitivity and trustworthiness. Conclusions: We argue that,
      to ensure good practice in EIP, procedural and substantive ethical expectations
      embedded in EIP guideline documents should be made explicit in EIP service and
      care delivery. We suggest that the procedural and substantive factors highlighted
      in this paper contribute useful dimensions for the eventual evaluation of good
      practice in EIP services across England.

PMID- 30197575
TI  - Exploring the feasibility and acceptability of a school-based self-referral
      intervention for emotional difficulties in older adolescents: qualitative
      perspectives from students and school staff.
AB  - Background: Adolescents with emotional difficulties need accessible, acceptable
      and evidence-based mental health interventions. Self-referral workshops (DISCOVER
      workshops) were offered to stressed 16- to 19-year olds in 10 Inner London
      schools. Method: Semistructured interviews were conducted with three groups of
      participants: students who attended a 1-day workshop (n = 15); students who
      initially showed interest in the DISCOVER workshop programme, but decided not to
      take part (n = 9); and school staff who helped organise the programme in their
      schools (n = 10). Students were purposively sampled to ensure that those from
      Black and minority ethnic (BME) backgrounds were represented. Data were analysed
      using thematic analysis. Results: The accounts generally indicate that the
      delivery and evaluation of this intervention is perceived as feasible and
      acceptable. Students, including those from BME backgrounds, described the setting
      as suitable and reported that the workshop helped them develop new understandings
      of stress and how to handle it. They expressed a preference for engaging and
      interactive activities, and valued a personalised approach to workshop provision.
      School staff felt that the workshop was in line with school values. They
      described some logistical barriers to providing the workshops in school settings,
      and expressed a desire for more information about the workshop in order to
      provide follow-up support. The main reason students gave for nonparticipation was
      limited time. Conclusions: Findings are discussed in relation to increasing the
      feasibility of implementing school-based psychological interventions and the
      value of providing access to mental health support in schools.

PMID- 30197576
TI  - The presentation of depression symptoms in attention-deficit/hyperactivity
      disorder: comparing child and parent reports.
AB  - Background: Attention-deficit/hyperactivity disorder (ADHD) frequently co-occurs
      with depression, and outcomes are poor when both are present. Little is known
      about whether depression symptoms present differently in ADHD compared to the
      general population, or how reliable young people with ADHD are at reporting these
      symptoms. This study aimed to describe depression symptoms in a clinical ADHD
      sample compared to a population sample, and compare self-reports of depression
      symptoms with parent-reports. Methods: Two hundred and forty-nine children with
      ADHD and their parents completed follow-up questionnaires around 5 years after
      taking part in a Cardiff University ADHD study. Child depression symptoms were
      measured using parent- and child-reported Mood and Feelings Questionnaires (MFQ)
      and compared to a population sample with MFQ data (n = 1460). Within both
      samples, child- and parent-reported depression symptoms were compared. Results:
      Although the profile of depression symptoms was similar between young people with
      ADHD and those in the general population, depression symptoms were much more
      common in the ADHD sample (parent-rated MFQ score = 24.52 vs. 9.39; child-rated =
      21.02 vs. 11.86). The most common symptoms in both samples included irritability,
      restlessness and concentration difficulties, with core depression symptoms such
      as feeling miserable/unhappy also prominent. Within the ADHD sample, but not the
      population sample, children reported depression symptoms less frequently than
      their parents. Conclusions: Young people with ADHD are at high risk of
      experiencing symptoms of depression but may under-report the severity of their
      symptoms. Obtaining parent reports of depression symptoms in this group may be
      important to avoid missing key indicators of risk.

PMID- 30197577
TI  - A depth dose study between AAA and AXB algorithm against Monte Carlo simulation
      using AIP CT of a 4D dataset from a moving phantom.
AB  - Aim: To identifying depth dose differences between the two versions of the
      algorithms using AIP CT of a 4D dataset. Background: Motion due to respiration
      may challenge dose prediction of dose calculation algorithms during treatment
      planning. Materials and methods: The two versions of depth dose calculation
      algorithms, namely, Anisotropic Analytical Algorithm (AAA) version 10.0
      (AAAv10.0), AAA version 13.6 (AAAv13.6) and Acuros XB dose calculation (AXB)
      algorithm version 10.0 (AXBv10.0), AXB version 13.6 (AXBv13.6), were compared
      against a full MC simulated 6X photon beam using QUASAR respiratory motion
      phantom with a moving chest wall. To simulate the moving chest wall, a 4 cm thick
      wax mould was attached to the lung insert of the phantom. Depth doses along the
      central axis were compared in the anterior and lateral beam direction for field
      sizes 2 * 2 cm2, 4 * 4 cm2 and 10 * 10 cm2. Results: For the lateral beam
      direction, the moving chest wall highlighted differences of up to 105% for
      AAAv10.0 and 40% for AXBv10.0 from MC calculations in the surface and buildup
      doses. AAAv13.6 and AXBv13.6 agrees with MC predictions to within 10% at similar
      depth. For anterior beam doses, dose differences predicted for both versions of
      AAA and AXB algorithm were within 7% and results were consistent with static
      heterogeneous studies. Conclusions: The presence of the moving chest wall was
      capable of identifying depth dose differences between the two versions of the
      algorithms. These differences could not be identified in the static chest wall as
      shown in the anterior beam depth dose calculations.

PMID- 30197578
TI  - The effect of beam shape on physical parameters of head and neck simultaneous
      integrated boost intensity-modulated radiation therapy.
AB  - Aim: To evaluate the influence of the beam shape created by X-rays with "flat
      beams" and without "flattening-filter-free [FFF] beams" a flattening filter, and
      the isocenter locations for FFF beams on the treatment of a large irradiated
      volume for tumours. Background: The increase of dose rate and the decrease of out
      of-field dose can be expected for FFF beams and lead to effective and safety
      radiotherapy. On the other hand, the bell-shaped dose profile is thought to be a
      factor of negating these advantages. Materials and methods: Treatment plans for
      15 patients with head and neck cancer were created using XiO (Elekta, Stockholm
      AB, Sweden) in fixed-gantry step-and-shoot delivery under the same dose
      constraints. Seven fields of FFF beams with 7 MV and flat beams with 6 MV were
      used with the technique of intensity-modulated radiation therapy (IMRT). We
      compared the dose homogeneity and conformity of targets and dose constraints for
      organs as the plan quality and evaluated physical parameters: monitor unit (MU)
      values, number of segments and their locations from the isocenter in beam's-eye
      view. Results: No significant differences were found in the plan quality. The
      isocenter locations do not affect the physical parameters for FFF beams. It has
      been confirmed that the number of segments and MU values were 40% higher with FFF
      beams than with flat beams (p < 0.05). Conclusion: This study demonstrates flat
      dose distribution is more suitable for IMRT with large and complex targets.

PMID- 30197579
TI  - Design of spread-out Bragg peaks in hadron therapy with oxygen ions.
AB  - Aim: Design of a numerical method for creating spread-out Bragg peak (SOBP) and
      evaluation of the best parameter in Bortfeld Model to this aim in oxygen ion
      therapy. Background: In radiotherapy, oxygen ions have more biological benefits
      than light beams. Oxygen ions have a higher linear energy transfer (LET) and
      larger relative biological effectiveness (RBE) than lighter ones. Materials and
      methods: For the design of the spread-out Bragg peak (SOBP) for oxygen beam, we
      designed a numerical method using the Geant4 Monte Carlo simulation code, along
      with matrix computations. Results: The profiles of the Bragg Peak have been
      calculated for each section in the target area by the Geant4 tool. Then, in order
      to produce SOBP smoothly, a set of weighting factors for the intensity of oxygen
      ion radiation in each energy was extracted through a numerically designed method.
      This method was tested for producing SOBP at various widths and at different
      depths of a phantom. Also, weighting factors of intensity for producing a flat
      SOBP with oxygen ions were also obtained using the Bortfeld model in order to
      determine the best parameters. Then, the results of the Bortfeld model were
      compared with the outcomes of the method that was developed in this study.
      Conclusions: The results showed that while the SOBP designed by the Bortfeld
      model has a homogeneity of 92-97%, the SOBP designed by the numerical method in
      the present study is above 99%, which in some cases even closed to 100%.

PMID- 30197582
TI  - Cultural antecedents to community: An evaluation of community experience in the
      United States, Thailand, and Vietnam.
AB  - To what extent does community experience differ between low context and high
      context societies? Prior literature theorizes that community experience consists
      of two separate, yet highly related concepts: community attachment, an
      individual's general rootedness to a place, and community satisfaction, how well
      an individual's community meets their societal needs. We test this
      conceptualization of community experience across communities in the US and two
      Southeast Asian nations: Thailand and Vietnam. We argue that Southeast Asian
      nations constitute "high context" societies with relatively high social
      integration and solidarity while the US is more individualized and less socially
      integrated and thus constitutes a "low context" society. Our results provide
      empirical evidence that individuals' experience of community varies between low
      and high context societies. These results demonstrate that cultural context
      continues to matter in regards to the lived experience of community and
      researchers need to remain vigilant in accounting for such differences as they
      seek to examine the concept of community more broadly.

PMID- 30197580
TI  - Interinstitutional patient transfers between rapid chemotherapy cycles were
      feasible to utilize proton beam therapy for pediatric Ewing sarcoma family of
      tumors.
AB  - Aim: To assess the feasibility of transferring to the University of Tsukuba
      Hospital for proton beam therapy (PBT) during intensive chemotherapy in children
      with Ewing sarcoma family of tumors (ESFT) who had been diagnosed and started
      their first-line treatment at prefectural or regional centers for pediatric
      oncology. Background: The treatment of ESFT relies on a multidisciplinary
      approach using intensive neoadjuvant and adjuvant chemotherapies with surgery and
      radiotherapy. Multi-agent chemotherapy comprising vincristine, doxorubicin,
      cyclophosphamide, ifosfamide, and etoposide (VDC-IE) is widely used for ESFT, and
      the interval between each course is very important for maintaining the intensity
      and effect of chemotherapy. Materials and methods: Clinical information of
      patients who received PBT and VDC-IE between April 2009 and May 2016 was
      collected retrospectively. The intervals between each course of VDC-IE and
      adverse events were assessed. Results: Fifteen patients were evaluated. No delays
      in the intervals of chemotherapy due to transfer were observed. There were no
      adverse events caused during/just after transfer and no increases in adverse
      events. The estimated 4-year overall and event-free survival rates were 94.6% and
      84.8%, respectively. Discussion: Although the results of efficacy are
      preliminary, survival rates were comparable with past studies. More experience
      and follow-up are required to further assess the efficacy of PBT for patients
      with ESFT. Conclusion: Multidisciplinary therapy for children with ESFT involving
      transfer to our hospital for PBT during VDC-IE was feasible without treatment
      delay or an increase in adverse events.

PMID- 30197581
TI  - Evaluating Caregiver Sensitivity to Infants: Measures Matter.
AB  - The significance of caregiver sensitivity for child development has been debated
      among scholars, not least due to sensitivity's inconsistent predictive value over
      time and across contexts. A lack of uniformity in the definition of sensitivity
      contributes to this debate, but shortfalls of inter-tool concordance and
      construct validity in the instruments used to assess sensitivity may also be at
      issue. This study examines correspondences among four established standardized
      measures of caregiver sensitivity in independent classifications of the same
      sample of mothers of infants. 50 European American mother- infant dyads of
      diverse SES were independently assessed with three observational caregiver
      sensitivity measures: the Emotional Availability Scales (EAS; Biringen, 2008),
      the Parent Child Interaction - Nursing Child Assessment Feeding Scale (PCI-NCAFS;
      Oxford & Findlay, 2015), and the Maternal Behaviour Q-Sort (MBQS; Moran, Pederson
      & Bento, 2009). Ratings were juxtaposed with classifications of the same sample
      based on the original Ainsworth Maternal Sensitivity Scales (AMSS; Ainsworth,
      1969). The EAS, NCAFS, and MBQS related to the AMSS, but large proportions of
      variance were unshared. Researchers and clinicians should be cautious when
      assuming that popular observational assessment instruments, commonly believed to
      measure a generic construct of caregiver sensitivity, are interchangeable, as
      these measures may evaluate different features of sensitivity to infants.

PMID- 30197583
TI  - Repeated Transarterial Chemoembolization with Degradable Starch ?Microspheres
      (DSMs-TACE) of Unresectable Hepatocellular Carcinoma: A Prospective Pilot Study.
AB  - OBJECTIVE: The aims of this study were to: a) evaluate tumor response rates using
      modified-Response-evaluation-criteria-in-solid-tumors (mRecist) criteria, b)
      evaluate safety of Degradable Starch Microspheres Trans-arterial-chemo
      embolization (DSMs-TACE) for unresectable hepatocellular-carcinoma (HCC)
      treatment. MATERIALS AND METHODS: We prospectively enrolled 24 HCC cirrhotic
      patients (21/3 M/F, mean age 66.3 years) to be treated with repeated DSMs-TACE
      procedures, performed at 4-6 week intervals on the basis of tumor response and
      patients tolerance. Clinical and biochemical evaluations were performed before
      and after each procedure. Treatment response was also assessed by Computed
      tomography (CT) or Magnetic-resonance-imaging (MRI)-scan 4-6 weeks following each
      procedure. RESULTS: In our experience, DSMs-TACE was both safe and effective. A
      total of 53 DSMs-TACE procedures were performed (2.2 per patient). No procedure
      related death was observed. Complete Response (CR) was observed in 5/24 (20.8%),
      4/17 (23.5%) and 5/12 (41.6%) patients after the first, second and third
      procedure, respectively. At the end of each treatment, all patients experienced
      at least a partial response. At the end of the repeated procedures, no
      differences between mono- or bi-lobar disease were observed in patients with CR
      (64.2% vs 50%; p=ns). In most cases, treatment discontinuation was due to
      worsening liver function. CONCLUSION: DSMs-TACE is a valid, well-tolerated
      alternative treatment to Lipiodol-TACE or DEB-TACE, as it has demonstrated to
      achieve a relatively high percentage of complete tumor necrosis. CR rates were
      similar between patients with mono- or bi-lobar disease indicating the
      possibility of carrying-out repeated procedure in a safe and effective way in
      both types of patients.

PMID- 30197584
TI  - Impaired Cognitive Functioning in Cochlear Implant Recipients Over the Age of 55
      Years: A Cross-Sectional Study Using the Repeatable Battery for the Assessment of
      Neuropsychological Status for Hearing-Impaired Individuals (RBANS-H).
AB  - Primary Objective: To compare cognitive functioning among experienced, unilateral
      cochlear implant (CI) recipients and normal-hearing (NH) controls by means of the
      Repeatable Battery for the Assessment of Neuropsychological Status for Hearing
      impaired individuals (RBANS-H). Methods: Sixty-one post-lingually and bilaterally
      severely hearing-impaired CI recipients (median age: 71.0, range: 58.3 to 93.9
      years) with at least 1 year of CI experience (median: 12.4, range: 1.1 to 18.6
      years) and 81 NH control participants (median age: 69.9, range: 50.1 to 87.1
      years) took part in this cross-sectional study. The RBANS-H was performed, as
      well as an audiometric assessment, including best-aided speech audiometry in
      quiet (monosyllabic words) and in noise (Leuven Intelligibility Sentences test).
      Results: The RBANS-H performances of the CI recipients (mean: 88.1 +/- 14.9) were
      significantly poorer than the those of the NH participants (mean: 100.5 +/-
      13.2), with correction of age, sex, and education differences (general linear
      model: p = 0.001). The mean difference, corrected for the effects of these three
      demographic factors, was 8.8 (+/- 2.5) points. Additionally, in both groups, a
      significant correlation was established between overall cognition and speech
      perception, both in quiet and in noise, independently of age. Conclusion:
      Experienced, unilateral CI recipients present subnormal cognitive functioning,
      beyond the effect of age, sex and education. This has implications for auditory
      rehabilitation after CI and may highlight the need for additional cognitive
      rehabilitation in the long term after implantation. Long-term prospective and
      longitudinal investigations are imperative to improve our understanding of
      cognitive aging in severely hearing-impaired individuals receiving CIs and its
      association with CI outcomes.

PMID- 30197585
TI  - Loss of alpha-Calcitonin Gene-Related Peptide (alphaCGRP) Reduces Otolith
      Activation Timing Dynamics and Impairs Balance.
AB  - Calcitonin gene-related peptide (CGRP) is a neuroactive peptide that is thought
      to play a role at efferent synapses in hair cell organs including the cochlea,
      lateral line, and semicircular canal. The deletion of CGRP in transgenic mice is
      associated with a significant reduction in suprathreshold cochlear nerve activity
      and vestibulo-ocular reflex (VOR) gain efficacy when compared to littermate
      controls. Here we asked whether the loss of CGRP also influences otolithic end
      organ function and contributes to balance impairments. Immunostaining for CGRP
      was absent in the otolithic end organs of alphaCGRP null (-/-) mice while choline
      acetyltransferase (ChAT) immunolabeling appeared unchanged suggesting the overall
      gross development of efferent innervation in otolithic organs was unaltered.
      Otolithic function was assessed by quantifying the thresholds, suprathreshold
      amplitudes, and latencies of vestibular sensory-evoked potentials (VsEPs) while
      general balance function was assessed using a modified rotarod assay. The loss of
      alphaCGRP in null (-/-) mice was associated with: (1) shorter VsEP latencies
      without a concomitant change in amplitude or thresholds, and (2) deficits in the
      rotarod balance assay. Our findings show that CGRP loss results in faster otolith
      afferent activation timing, suggesting that the CGRP component of the efferent
      vestibular system (EVS) also plays a role in otolithic organ dynamics, which when
      coupled with reduced VOR gain efficacy, impairs balance.

PMID- 30197586
TI  - Human Tau Expression Does Not Induce Mouse Retina Neurodegeneration, Suggesting
      Differential Toxicity of Tau in Brain vs. Retinal Neurons.
AB  - The implication of the microtubule-associated protein (MAP) Tau in the ocular
      manifestations of Alzheimer's disease (AD) is elusive due to the lack of relevant
      animal model. However, signs of AD have been reported in the brain of transgenic
      mice expressing human Tau (hTau). To assess whether hTau is sufficient to induce
      AD pathogenesis in the retina as well, in the present study, we compared the
      retinal structure and function of KO mice deprived of Tau (mTKO) with those of
      transgenic mice expressing hTau. Our results revealed that hTau is particularly
      abundant in the inner nuclear layer (INL) cells of the retina. By
      electroretinogram (ERG) recording, light-induced retinal cell activation was not
      altered in hTau compared with mTKO littermates. Surprisingly, the ERG response
      mediated by cone photoreceptor stimulation was even stronger in hTau than in mTKO
      retinae. Immunofluorescent analysis of retinal sections allowed us to observe
      thicker inner retina in hTau than in mTKO eyes. By Western Blotting (WB), the
      upregulation of mTOR that was found in hTau mice may underlie retinal structure
      and function increases. Taken together, our results not only indicate that hTau
      expression is not toxic for retinal cells but they also suggest that it may play
      a positive role in visual physiology. The use of hTau may be envisaged to improve
      visual recovery in ocular diseases affecting the retinal function such as
      glaucoma or diabetic retinopathy.

PMID- 30197587
TI  - Anxiety Specific Response and Contribution of Active Hippocampal Neural Stem
      Cells to Chronic Pain Through Wnt/beta-Catenin Signaling in Mice.
AB  - Chronic pain usually results in persistent anxiety, which worsens the life
      quality of patients and complicates the treatment of pain. Hippocampus is one of
      the few brain regions in many mammalians species which harbors adult neural stem
      cells (NSCs), and plays a key role in the development and maintenance of chronic
      anxiety. Recent studies have suggested a potential involvement of hippocampal
      neurogenesis in modulating chronic pain. Whether and how hippocampal NSCs are
      involved in the pain-associated anxiety remains unclear. Here, we report that
      mice suffering persistent neuropathic pain showed a quick reduction of active
      NSCs in the ventral dentate gyrus (vDG), which was followed by the decrease of
      neurogenesis and appearance of anxiety. Wnt/beta-catenin signaling, a key pathway
      in sustaining the active status of NSCs was suppressed in the vDG of mice
      suffering chronic pain. Depleting beta-catenin by inducible Nestin-Cre
      significantly reduced the number of active NSCs and facilitated anxiety
      development, while expressing stabilized beta-catenin amplified active NSCs and
      alleviated anxiety, indicating that Wnt activated NSCs is required for anxiety
      development under chronic pain. Treatment with Fluoxetine, the most widely used
      anxiolytic in clinic, significantly increased the proliferation of active NSCs
      and enhanced Wnt signaling. Interestingly, both beta-catenin manipulation and
      Fluoxetine treatment had no significant effects on the pain thresholds.
      Therefore, our data demonstrated an anxiety-specific response and contribution of
      activated NSCs to chronic pain through Wnt/beta-catenin signaling, which may be
      targeted for treating chronic pain- or other diseases-associated anxiety.

PMID- 30197589
TI  - Astrocytes Protect Neurons in the Hippocampal CA3 Against Ischemia by Suppressing
      the Intracellular Ca2+ Overload.
AB  - In the hippocampus, delayed neuronal death is normally seen in neurons of the CA1
      region but not in those of the CA3 region. Astrocytes have been reported to play
      multiple supporting or pathological roles in neuronal functioning. While evidence
      indicates that astrocytes could exert neuroprotective effects following ischemia,
      the possible underlying mechanisms remain unclear. We aimed to investigate the
      roles of astrocytes in the process of delayed neuronal death following transient
      forebrain ischemia. L-alpha-aminoadipic acid (L-alpha-AAA), an astrocyte
      selective gliotoxin, was injected into the hippocampal CA3 region of rats through
      a cranial window to selectively damage astrocytes. Immunofluorescence staining of
      glial fibrillary acidic protein (GFAP) was used to evaluate the effect of L-alpha
      AAA on astrocyte numbers. Three days after the L-alpha-AAA injection, transient
      forebrain ischemia was induced by a modification of the four-vessel occlusion
      procedure. Seven days after transient forebrain ischemia, hematoxylin-eosin
      staining was performed to reveal the morphology of hippocampal pyramidal neurons.
      In rats with ischemia and reperfusion, regional cerebral blood flow (rCBF) and
      change in intracellular Ca2+ concentration ([Ca2+]i) were separately measured in
      CA1 and CA3 regions. L-alpha-AAA injection significantly decreased the number of
      astrocytes in CA3, but did not affect the pattern of rCBF changes upon
      ischemia/reperfusion. Seven days after transient forebrain ischemia, in rats
      receiving L-alpha-AAA, delayed neuronal death comparable with that in CA1 was
      observed in the CA3 region. In addition, the pattern of increase in [Ca2+]i due
      to transient forebrain ischemia was completely changed in the hippocampal CA3.
      The loss of astrocytes induced a persistent increase in [Ca2+]i in the CA3 region
      following transient ischemia, similar to what is observed in the CA1 region. Our
      study indicates that astrocytes in the hippocampal CA3 region exert
      neuroprotective effects following transient forebrain ischemia and act by
      suppressing the intracellular Ca2+ overload. Furthermore, our study will most
      likely provide a new therapeutic strategy for brain ischemic diseases, targeted
      to astrocytes.

PMID- 30197588
TI  - SUMOylation of Alpha-Synuclein Influences on Alpha-Synuclein Aggregation Induced
      by Methamphetamine.
AB  - Methamphetamine (METH) is an illegal and widely abused psychoactive stimulant.
      METH abusers are at high risk of neurodegenerative disorders, including
      Parkinson's disease (PD). Previous studies have demonstrated that METH causes
      alpha-synuclein (alpha-syn) aggregation in the both laboratory animal and human.
      In this study, exposure to high METH doses increased the expression of alpha-syn
      and the small ubiquitin-related modifier 1 (SUMO-1). Therefore, we hypothesized
      that SUMOylation of alpha-syn is involved in high-dose METH-induced alpha-syn
      aggregation. We measured the levels of alpha-syn SUMOylation and these enzymes
      involved in the SUMOylation cycle in SH-SY5Y human neuroblastoma cells (SH-SY5Y
      cells), in cultures of C57 BL/6 primary mouse neurons and in brain tissues of
      mice exposure to METH. We also demonstrated the effect of alpha-syn SUMOylation
      on alpha-syn aggregation after METH exposure by overexpressing the key enzyme of
      the SUMOylation cycle or silencing SUMO-1 expression in vitro. Then, we make
      introduced mutations in the major SUMOylation acceptor sites of alpha-syn by
      transfecting a lentivirus containing the sequence of WT alpha-syn or K96/102R
      alpha-syn into SH-SY5Y cells and injecting an adenovirus containing the sequence
      of WT alpha-syn or K96/102R alpha-syn into the mouse striatum. Levels of the
      ubiquitin-proteasome system (UPS)-related makers ubiquitin (Ub) and UbE1, as well
      as the autophagy-lysosome pathway (ALP)-related markers LC3, P62 and lysosomal
      associated membrane protein 2A (LAMP2A), were also measured in SH-SY5Y cells
      transfected with lentivirus and mice injected with adenovirus. The results showed
      that METH exposure decreases the SUMOylation level of alpha-syn, although the
      expression of alpha-syn and SUMO-1 are increased. One possible cause is the
      reduction of UBC9 level. The increase in alpha-syn SUMOylation by UBC9
      overexpression relieves METH-induced alpha-syn overexpression and aggregation,
      whereas the decrease in alpha-syn SUMOylation by SUMO-1 silencing exacerbates the
      same pathology. Furthermore, mutations in the major SUMOylation acceptor sites of
      alpha-syn also aggravate alpha-syn overexpression and aggregation by impairing
      degradation through the UPS and the ALP in vitro and in vivo. These results
      suggest that SUMOylation of alpha-syn plays a fundamental part in alpha-syn
      overexpression and aggregation induced by METH and could be a suitable target for
      the treatment of neurodegenerative diseases.

PMID- 30197590
TI  - More Than Meets the Eye: The Impact of Materialism on Information Selection
      During Luxury Choices.
AB  - Visual attention is an important condition for consumer decision-making. However,
      not much is known on individuals' determinants of this visual attention. Using
      eye tracking, this study investigated how psychological values (i.e.,
      materialism) modulate visual attention to specific sources of information (i.e.,
      product, brand and additional information) in the context of luxury consumption.
      Participants were asked to perform a forced-choice experiment, where products
      were randomly assigned with luxury and non-luxury brands (Experiment 1) and
      product information (Experiment 2). Experiment 1 revealed that materialism was
      related to relatively higher attention to luxury as opposed to non-luxury and
      higher choice proportion of products displayed with a luxury brand. Experiment 2
      showed that when providing additional product information (e.g., regarding the
      material) in addition to the brand, all participants chose luxury products more
      often. Interestingly, choices seemed to be driven by enhanced attention to brand
      for participants with high levels of materialism when choosing luxury products.
      In contrast, choices were driven by text for participants with low levels of
      materialism for non-luxury products. This suggests that individuals with high
      levels of materialism may prefer luxury products for different reasons than
      individuals with low levels of materialism: while the first focus on the symbolic
      dimension conveyed by the brand (Experiment 1), the latter pay attention to the
      actual product characteristics (Experiment 2). Taken together, our results
      suggest that materialism as a psychological value has an impact on visual
      attention and information selection during decision-making in the context of
      luxury consumption.

PMID- 30197591
TI  - Adolescent Changes in Cellular Proliferation in the Dentate Gyrus of Male and
      Female C57BL/6N Mice Are Resilient to Chronic Oral Corticosterone Treatments.
AB  - Adolescent development is marked by significant changes in neurobiological
      structure and function. One such change is the substantial adolescent-related
      decline in cellular proliferation and neurogenesis in the dentate gyrus of the
      hippocampal formation. Though the behavioral implications of these developmental
      shifts in cell proliferation are unclear, these changes might contribute to the
      altered cognitive and emotional functions associated with puberty and
      adolescence. The significant decrease in cellular proliferation throughout
      adolescence might make the hippocampus more vulnerable to perturbations during
      this developmental stage, particularly to factors known to disrupt neurogenesis,
      such as chronic exposure to stress-related hormones. To examine this possibility,
      we first measured cellular proliferation in the dentate gyrus of male and female
      C57BL/6N mice before and after adolescence and then assessed both cellular
      proliferation and the number of immature neurons in mice treated with oral
      corticosterone for 4 weeks during either adolescence or adulthood. We found
      significant age-related decreases in hippocampal cellular proliferation in both
      males and females. Though the greatest decrease in proliferation was during
      adolescence, we also observed that proliferation continued to decline through
      young adulthood. Despite the significant effect of chronic oral corticosterone on
      body weight gain in both the adolescent- and adult-treated males and females and
      the subtle, but significant suppressive effect of corticosterone on the number of
      immature neurons in the adolescent-treated males, cell proliferation in the
      hippocampus was unaffected by these treatments. These data show that the
      substantial adolescent-related change in cellular proliferation in the dentate
      gyrus is largely unaffected by chronic oral corticosterone exposure in males and
      females. Thus, despite being vulnerable to the metabolic effects of these chronic
      corticosterone treatments, these results indicate that the developmental changes
      in cellular proliferation in the dentate gyrus are relatively resilient to these
      treatments in mice.

PMID- 30197592
TI  - Cathodal tDCS Over Motor Cortex Does Not Improve Tourette Syndrome: Lessons
      Learned From a Case Series.
AB  - Introduction: Current pathophysiological hypotheses of Gilles de la Tourette
      Syndrome (GTS) refer to temporally abnormal neuronal activation in cortico
      striato-thalamo-cortical (CSTC) networks. Modifying cortical activity by non
      invasive brain-stimulation appears to be a new treatment option in GTS.
      Background: Previous studies suggested therapeutic effects of cathodal
      transcranial direct current stimulation (tDCS) to pre-supplementary motor areas
      (SMA), however, treatment modalities concerning electrode placement, current
      intensity and stimulation-rate have not been systematically explored. Aim of this
      study was to assess efficacy of an alternative stimulation regime on GTS symptoms
      in a pilot study. To test a treatment protocol with tDCS twice a day, we
      administered 10 sessions over 5 days of bilateral cathodal tDCS (30 min, 2 mA)
      over the pre-SMA in three patients with severe GTS. Tic severity as well as
      obsessive-compulsive (OC) symptoms and affective scales were rated before and
      after tDCS treatment. Discussion: Only one out of three patients showed a 34.5%
      reduction in tic severity. The two other patients showed an increase in tic
      severity. All patients showed a mild increase in positive affect and a reduction
      in negative affect, OC symptom changes were heterogeneous. Our results do not
      support earlier findings of extensive therapeutic effects of cathodal tDCS on
      tics in patients with GTS and show that prediction of stimulation effects on a
      targeted brain area remains inaccurate. Concluding Remarks: Future research will
      have to focus on the determination of most effective stimulation modes regarding
      site, polarity and frequency of tDCS in GTS patients.

PMID- 30197594
TI  - Interleukin-35 Attenuates D-Galactosamine/Lipopolysaccharide-Induced Liver Injury
      via Enhancing Interleukin-10 Production in Kupffer Cells.
AB  - Interleukin (IL) -35 is an anti-inflammatory cytokine which exerts various
      beneficial effects on autoimmune diseases. However, whether IL-35 plays a role in
      endotoxin induced hepatitis demands clarification. This study aims to reveal the
      effect and mechanism of IL-35 on endotoxin induced liver injury. Acute hepatic
      injury was induced by D-galactosamine (D-GalN, 400 mg/kg) and lipopolysaccharide
      (LPS, 5 MUg/kg) administration in mice. IL-35 treatment ameliorated D-GalN/LPS
      induced liver injury in a dose dependent manner as shown by histological
      examination, ALT determination and Caspase-3 activity assay. It also reduced
      production of pro-inflammatory cytokines, tumor necrosis factor (TNF)-alpha, IL
      1beta, and IL-6, and increased production of anti-inflammatory cytokines, IL-4,
      IL-10, and transforming growth factor (TGF)-beta. This hepato-protective effect
      was proved mainly mediated by Kupffer cells (KC) via gadolinium chloride
      depletion and cell adoptive transfer experiment. In addition, IL-35 emolliated
      the cytotoxicity of LPS-triggered KCs to hepatocytes, suppressed nitric oxide
      (NO) and TNF-alpha production, and elevated IL-10 production in LPS stimulated
      KCs. Furthermore, IL-35 could not exert hepato-protective effect in IL-10
      deficient mice in vivo and it could not suppress LPS induced NO and TNF-alpha
      production in IL-10-deficient KCs in vitro. In conclusion, IL-35 protects
      endotoxin-induced acute liver injury, which mainly acts thought increasing IL-10
      production in KCs. This finding demonstrates a role of IL-35 in anti-infectious
      immunity and provides a potential therapeutic target in treating fulminant
      hepatitis.

PMID- 30197593
TI  - Neuroscience Information Toolbox: An Open Source Toolbox for EEG-fMRI Multimodal
      Fusion Analysis.
AB  - Recently, scalp electroencephalography (EEG) and functional magnetic resonance
      imaging (fMRI) multimodal fusion has been pursued in an effort to study human
      brain function and dysfunction to obtain more comprehensive information on brain
      activity in which the spatial and temporal resolutions are both satisfactory.
      However, a more flexible and easy-to-use toolbox for EEG-fMRI multimodal fusion
      is still lacking. In this study, we therefore developed a freely available and
      open-source MATLAB graphical user interface toolbox, known as the Neuroscience
      Information Toolbox (NIT), for EEG-fMRI multimodal fusion analysis. The NIT
      consists of three modules: (1) the fMRI module, which has batch fMRI
      preprocessing, nuisance signal removal, bandpass filtering, and calculation of
      resting-state measures; (2) the EEG module, which includes artifact removal,
      extracting EEG features (event onset, power, and amplitude), and marking
      interesting events; and (3) the fusion module, in which fMRI-informed EEG
      analysis and EEG-informed fMRI analysis are included. The NIT was designed to
      provide a convenient and easy-to-use toolbox for researchers, especially for
      novice users. The NIT can be downloaded for free at
      http://www.neuro.uestc.edu.cn/NIT.html, and detailed information, including the
      introduction of NIT, user's manual and example data sets, can also be observed on
      this website. We hope that the NIT is a promising toolbox for exploring brain
      information in various EEG and fMRI studies.

PMID- 30197595
TI  - Relationship of Transmural Variations in Myofiber Contractility to Left
      Ventricular Ejection Fraction: Implications for Modeling Heart Failure Phenotype
      With Preserved Ejection Fraction.
AB  - The pathophysiological mechanisms underlying preserved left ventricular (LV)
      ejection fraction (EF) in patients with heart failure and preserved ejection
      fraction (HFpEF) remain incompletely understood. We hypothesized that transmural
      variations in myofiber contractility with existence of subendocardial dysfunction
      and compensatory increased subepicardial contractility may underlie preservation
      of LVEF in patients with HFpEF. We quantified alterations in myocardial function
      in a mathematical model of the human LV that is based on the finite element
      method. The fiber-reinforced material formulation of the myocardium included
      passive and active properties. The passive material properties were determined
      such that the diastolic pressure-volume behavior of the LV was similar to that
      shown in published clinical studies of pressure-volume curves. To examine changes
      in active properties, we considered six scenarios: (1) normal properties
      throughout the LV wall; (2) decreased myocardial contractility in the
      subendocardium; (3) increased myocardial contractility in the subepicardium; (4)
      myocardial contractility decreased equally in all layers, (5) myocardial
      contractility decreased in the midmyocardium and subepicardium, (6) myocardial
      contractility decreased in the subepicardium. Our results indicate that decreased
      subendocardial contractility reduced LVEF from 53.2 to 40.5%. Increased
      contractility in the subepicardium recovered LVEF from 40.5 to 53.2%. Decreased
      contractility transmurally reduced LVEF and could not be recovered if
      subepicardial and midmyocardial contractility remained depressed. The
      computational results simulating the effects of transmural alterations in the
      ventricular tissue replicate the phenotypic patterns of LV dysfunction observed
      in clinical practice. In particular, data for LVEF, strain and displacement are
      consistent with previous clinical observations in patients with HFpEF, and
      substantiate the hypothesis that increased subepicardial contractility may
      compensate for subendocardial dysfunction and play a vital role in maintaining
      LVEF.

PMID- 30197596
TI  - Insulin-Like Peptides Regulate Feeding Preference and Metabolism in Drosophila.
AB  - Fruit flies have eight identified Drosophila insulin-like peptides (DILPs) that
      are involved in the regulation of carbohydrate concentrations in hemolymph as
      well as in accumulation of storage metabolites. In the present study, we
      investigated diet-dependent roles of DILPs encoded by the genes dilp1-5, and
      dilp7 in the regulation of insect appetite, food choice, accumulation of
      triglycerides, glycogen, glucose, and trehalose in fruit fly bodies and
      carbohydrates in hemolymph. We have found that the wild type and the mutant lines
      demonstrate compensatory feeding for carbohydrates. However, mutants on dilp2,3,
      dilp3, dilp5, and dilp7 showed higher consumption of proteins on high yeast
      diets. To evaluate metabolic differences between studied lines on different diets
      we applied response surface methodology. High nutrient diets led to a moderate
      increase in concentration of glucose in hemolymph of the wild type flies.
      Mutations on dilp genes changed this pattern. We have revealed that the dilp2
      mutation led to a drop in glycogen levels independently on diet, lack of dilp3
      led to dramatic increase in circulating trehalose and glycogen levels, especially
      at low protein consumption. Lack of dilp5 led to decreased levels of glycogen and
      triglycerides on all diets, whereas knockout on dilp7 caused increase in glycogen
      levels and simultaneous decrease in triglyceride levels at low protein
      consumption. Fruit fly appetite was influenced by dilp3 and dilp7 genes. Our data
      contribute to the understanding of Drosophila as a model for further studies of
      metabolic diseases and may serve as a guide for uncovering the evolution of
      metabolic regulatory pathways.

PMID- 30197597
TI  - The Maximum Lyapunov Exponent During Walking and Running: Reliability Assessment
      of Different Marker-Sets.
AB  - The maximum Lyapunov exponent (MLE) has often been suggested as the prominent
      measure for evaluation of dynamic stability of locomotion in pathological and
      healthy population. Although the popularity of the MLE has increased in the last
      years, there is scarce information on the reliability of the method, especially
      during running. The purpose of the current study was, thus, to examine the
      reliability of the MLE during both walking and running. Sixteen participants
      walked and ran on a treadmill completing two measurement blocks (i.e., two trials
      per day for three consecutive days per block) separated by 2 months on average.
      Six different marker-sets on the trunk were analyzed. Intraday, interday and
      between blocks reliability was assessed using the intraclass correlation
      coefficient (ICC) and the root mean square difference (RMSD). The MLE was on
      average significantly higher (p < 0.001) in running (1.836 +/- 0.080) compared to
      walking (1.386 +/- 0.207). All marker-sets showed excellent ICCs (>0.90) during
      walking and mostly good ICCs (>0.75) during running. The RMSD ranged from 0.023
      to 0.047 for walking and from 0.018 to 0.050 for running. The reliability was
      better when comparing MLE values between blocks (ICCs: 0.965-0.991 and 0.768
      0.961; RMSD: 0.023-0.034 and 0.018-0.027 for walking and running respectively),
      and worse when considering trials of the same day (ICCs: 0.946-0.980 and 0.739
      0.844; RMSD: 0.042-0.047 and 0.045-0.050 for walking and running respectively).
      Further, different marker-sets affect the reliability of the MLE in both walking
      and running. Our findings provide evidence that the assessment of dynamic
      stability using the MLE is reliable in both walking and running. More trials
      spread over more than 1 day should be considered in study designs with increased
      demands of accuracy independent of the locomotion condition.

PMID- 30197599
TI  - Short-Term Preconditioning With Blood Flow Restricted Exercise Preserves
      Quadriceps Muscle Endurance in Patients After Anterior Cruciate Ligament
      Reconstruction.
AB  - Surgical ACL reconstruction performed with a tourniquet induces compression and
      ischemic stress of the quadriceps femoris (QF) muscle which can accelerate
      postoperative weakness. Given that low-load blood flow restricted (BFR) exercise
      is potent in enhancing muscle oxygenation and vascular function, we hypothesized
      that short-term preconditioning with low-load BFR exercise can attenuate QF
      muscle endurance deterioration in the postoperative period. Twenty subjects
      undergoing arthroscopic ACL reconstruction performed 5 exercise sessions in the
      last 8 days prior to surgery. They were assigned into either BFR group,
      performing low-load BFR knee-extension exercise, or SHAM-BFR group, replicating
      equal training volume with sham occlusion. Blood flow (near-infrared
      spectroscopy) and surface EMG of QF muscle during sustained isometric contraction
      at 30% of maximal voluntary isometric contraction (MVIC) torque performed to
      volitional failure were measured prior to the intervention and again 4 and 12
      weeks after surgery. There was an overall decrease (p = 0.033) in MVIC torque
      over time, however, no significant time-group interaction was found. The time of
      sustained QF contraction shortened (p = 0.002) in SHAM-BFR group by 97 +/- 85 s
      at week 4 and returned to preoperative values at week 12. No change in the time
      of sustained contraction was detected in BFR group at any time point after
      surgery. RMS EMG amplitude increased (p = 0.009) by 54 +/- 58% at week 4 after
      surgery in BFR group only. BFm increased (p = 0.004) by 52 +/- 47% in BFR group,
      and decreased (p = 0.023) by 32 +/- 19% in SHAM-BFR group at week 4 after
      surgery. Multivariate regression models of postoperative changes in time of
      sustained QF contraction revealed its high correlation (R2 = 0.838; p < 0.001)
      with changes in BFm and RMS EMG in the SHAM-BFR group, whereas no such
      association was found in the BFR group. In conclusion, enhanced endurance of QF
      muscle was triggered by combination of augmented muscle fiber recruitment and
      enhanced muscle perfusion. The latter alludes to a preserving effect of
      preconditioning with BFR exercise on density and function of QF muscle
      microcirculation within the first 4 weeks after ACL reconstruction.

PMID- 30197601
TI  - Exosomes From Human Cardiac Progenitor Cells for Therapeutic Applications:
      Development of a GMP-Grade Manufacturing Method.
AB  - Exosomes, nanosized membrane vesicles secreted by cardiac progenitor cells (Exo
      CPC), inhibit cardiomyocyte apoptosis under stress conditions, promote
      angiogenesis in vitro, and prevent the early decline in cardiac function after
      myocardial infarction in vivo in preclinical rat models. The recognition of
      exosome-mediated effects has moved attempts at developing cell-free approaches
      for cardiac repair. Such approaches offer major advantages including the fact
      that exosomes can be stored as ready-to-use agents and delivered to patients with
      acute coronary syndromes. The aim of the present work was the development of a
      good manufacturing practice (GMP)-grade method for the large-scale preparation of
      Exo-CPC as a medicinal product, for a future clinical translation. A GMP
      compliant manufacturing method was set up, based on large-scale cell culture in
      xeno-free conditions, collection of up to 8 l of exosome-containing conditioned
      medium and isolation of Exo-CPC through tangential flow filtration. Quality
      control tests were developed and carried out to evaluate safety, identity, and
      potency of both cardiac progenitor cells (CPC) as cell source and Exo-CPC as
      final product (GMP-Exo-CPC). CPC, cultured in xeno-free conditions, showed a
      lower doubling-time than observed in research-grade condition, while producing
      exosomes with similar features. Cells showed the typical phenotype of mesenchymal
      progenitor cells (CD73/CD90/CD105 positive, CD14/CD20/CD34/CD45/HLA-DR negative),
      and expressed mesodermal (TBX5/TBX18) and cardiac-specific (GATA4/MESP1)
      transcription factors. Purified GMP-Exo-CPC showed the typical nanoparticle
      tracking analysis profile and expressed main exosome markers
      (CD9/CD63/CD81/TSG101). The GMP manufacturing method guaranteed high exosome
      yield (>1013 particles) and consistent removal (>=97%) of contaminating proteins.
      The resulting GMP-Exo-CPC were tested for safety, purity, identity, and potency
      in vitro, showing functional anti-apoptotic and pro-angiogenic activity. The
      therapeutic efficacy was validated in vivo in rats, where GMP-Exo-CPC ameliorated
      heart function after myocardial infarction. Our standardized production method
      and testing strategy for large-scale manufacturing of GMP-Exo-CPC open new
      perspectives for reliable human therapeutic applications for acute myocardial
      infarction syndrome and can be easily applied to other cell sources for different
      therapeutic areas.

PMID- 30197598
TI  - Sense and Insensibility - An Appraisal of the Effects of Clinical Anesthetics on
      Gastropod and Cephalopod Molluscs as a Step to Improved Welfare of Cephalopods.
AB  - Recent progress in animal welfare legislation stresses the need to treat
      cephalopod molluscs, such as Octopus vulgaris, humanely, to have regard for their
      wellbeing and to reduce their pain and suffering resulting from experimental
      procedures. Thus, appropriate measures for their sedation and analgesia are being
      introduced. Clinical anesthetics are renowned for their ability to produce
      unconsciousness in vertebrate species, but their exact mechanisms of action still
      elude investigators. In vertebrates it can prove difficult to specify the
      differences of response of particular neuron types given the multiplicity of
      neurons in the CNS. However, gastropod molluscs such as Aplysia, Lymnaea, or
      Helix, with their large uniquely identifiable nerve cells, make studies on the
      cellular, subcellular, network and behavioral actions of anesthetics much more
      feasible, particularly as identified cells may also be studied in culture,
      isolated from the rest of the nervous system. To date, the sorts of study
      outlined above have never been performed on cephalopods in the same way as on
      gastropods. However, criteria previously applied to gastropods and vertebrates
      have proved successful in developing a method for humanely anesthetizing Octopus
      with clinical doses of isoflurane, i.e., changes in respiratory rate, color
      pattern and withdrawal responses. However, in the long term, further refinements
      will be needed, including recordings from the CNS of intact animals in the
      presence of a variety of different anesthetic agents and their adjuvants. Clues
      as to their likely responsiveness to other appropriate anesthetic agents and
      muscle relaxants can be gained from background studies on gastropods such as
      Lymnaea, given their evolutionary history.

PMID- 30197600
TI  - Odorant Receptors and Odorant-Binding Proteins as Insect Pest Control Targets: A
      Comparative Analysis.
AB  - Recently, two alternative targets in insect periphery nerve system have been
      explored for environmentally-friendly approaches in insect pest management,
      namely odorant-binding proteins (OBPs) and odorant receptors (ORs). Located in
      insect antennae, OBPs are thought to be involved in the transport of odorants to
      ORs for the specific signal transduction of behaviorally active odorants. There
      is rich information on OBP binding affinity and molecular docking to bioactive
      compounds as well as ample 3D crystal structures due to feasible production of
      recombinant proteins. Although these provide excellent opportunities for them to
      be considered as pest control targets and a tool to design pest control agents,
      the debates on their binding specificity represent an obstacle. On the other
      hand, ORs have recently been functionally characterized with increasing evidence
      for their specificity, sensitivity and functional roles in pest behaviors.
      However, a major barrier to use ORs for semiochemical discovery is the lack of 3D
      crystal structures. Thus, OBPs and ORs have not been analyzed comparatively
      together so far for their feasibility as pest control targets. Here, we summarize
      the state of OBPs and ORs research in terms of its application in insect pest
      management. We discuss the suitability of both proteins as pest control targets
      and their selection toward the discovery of new potent semiochemicals. We argue
      that both proteins represent promising targets for pest control and can be used
      to identify new super-ligands likely present in nature and with reduced risk of
      resistance development than insect pesticides currently used in agriculture. We
      discuss that with the massive identification of OBPs through RNA-seq and improved
      binding affinity measurements, these proteins could be reconsidered as suitable
      targets for semiochemical discovery.

PMID- 30197602
TI  - The Role of Oxidative Stress in the Development of Systemic Sclerosis Related
      Vasculopathy.
AB  - Systemic sclerosis (SSc) is a rare connective tissue disease characterized by
      autoimmunity, vasculopathy, and progressive fibrosis typically affecting multiple
      organs including the skin. SSc often is a lethal disorder, because effective
      disease-modifying treatment still remains unavailable. Vasculopathy with
      endothelial dysfunction, perivascular infiltration of mononuclear cells, vascular
      wall remodeling and rarefaction of capillaries is the hallmark of the disease.
      Most patients present with vasospastic attacks of the digital arteries referred
      to as 'Raynaud's phenomenon,' which is often an indication of an underlying
      widespread vasculopathy. Although autoimmune responses and inflammation are both
      found to play an important role in the pathogenesis of this vasculopathy, no
      definite initiating factors have been identified. Recently, several studies have
      underlined the potential role of oxidative stress in the pathogenesis of SSc
      vasculopathy thereby proposing a new aspect in the pathogenesis of this disease.
      For instance, circulating levels of reactive oxygen species (ROS) related markers
      have been found to correlate with SSc vasculopathy, the formation of fibrosis and
      the production of autoantibodies. Excess ROS formation is well-known to lead to
      endothelial cell (EC) injury and vascular complications. Collectively, these
      findings suggest a potential role of ROS in the initiation and progression of SSc
      vasculopathy. In this review, we present the background of oxidative stress
      related processes (e.g., EC injury, autoimmunity, inflammation, and vascular wall
      remodeling) that may contribute to SSc vasculopathy. Finally, we describe the use
      of oxidative stress related read-outs as clinical biomarkers of disease activity
      and evaluate potential anti-oxidative strategies in SSc.

PMID- 30197604
TI  - Influence of Age on Cardiorespiratory Kinetics During Sinusoidal Walking in
      Humans.
AB  - We sought to determine the influence of age on cardiorespiratory kinetics during
      sinusoidal walking in two groups: 13 healthy young subjects (YG; 7 men and 6
      women, age 21 +/- 2 years) and 15 healthy elderly subjects (ELD; 9 men and 6
      women, age 67 +/- 5 years). A treadmill's speed was sinusoidally changed between
      3 and 6 km h-1 in the YG and between 3 and 5 km h-1 in the ELD during periods of
      1, 2, 5, and 10 min, and in a stepwise manner. We compared the groups' heart rate
      (HR), ventilation ( VE), and gas exchange (CO2 output ( V CO2) and O2 uptake ( V
      O2)) responses. We determined the phase shift (PS) and the normalized amplitude
      (Amp) ratio of these kinetics in relation to the sinusoidal change in walking
      speed in response to the magnitude from the maximum to minimum speeds as revealed
      by a Fourier analysis in all cardiorespiratory variables. Both the Amp ratio and
      PS in the VE, V CO2, and V O2 responses were very similar between the ELD and YG,
      and being independent of the periods of sinusoidal oscillations. In marked
      contrast, the PS of the HR kinetics was significantly slowed in the ELD compared
      to the YG. The Amp ratio of HR was not related to the covariance variation of HR
      (CVHR) at standing rest in the ELD. The HR kinetics during sinusoidal walking may
      not be attributable to parasympathetic nerve activity into the heart in the ELD.
      The slope of the Amp of VE related to the Amp of V CO2 ( VE/ V CO2 slope) was
      steeper in the ELD (0.0258) compared to the YG (0.0132), suggesting that exercise
      hyperpnea could be greatly induced during walking in the ELD. These findings
      suggest that aging influences the alterations of autonomic nervous system
      dependent slower HR kinetics and exercise hyperpnea during walking in the ELD.

PMID- 30197603
TI  - Calcitriol, the Bioactive Metabolite of Vitamin D, Increases Ventricular K+
      Currents in Isolated Mouse Cardiomyocytes.
AB  - Calcitriol, the bioactive metabolite of vitamin D, interacts with the
      ubiquitously expressed nuclear vitamin D receptor (VDR) to induce genomic
      effects, but it can also elicit rapid responses via membrane-associated VDR
      through mechanisms that are poorly understood. The down-regulation of K+ currents
      is the main origin of electrophysiological remodeling in pathological hypertrophy
      and heart failure (HF), which can contribute to action potential prolongation and
      subsequently increase the risk of triggered arrhythmias. Adult mouse ventricular
      myocytes were isolated and treated with 10 nM calcitriol or vehicle for 15-30
      min. In some experiments, cardiomyocytes were pretreated with the Akt inhibitor
      triciribine. In the adult mouse ventricle, outward K+ currents involved in
      cardiac repolarization are comprised of three components: the fast transient
      outward current (Itof), the ultrarapid delayed rectifier K+ current (Ikur), and
      the non-inactivating steady-state outward current (Iss). K+ currents were
      investigated using the whole-cell or the perforated patch-clamp technique and
      normalized to cell capacitance to obtain current densities. Calcitriol treatment
      of cardiomyocytes induced an increase in the density of Itof and Ikur, which was
      lost in myocytes isolated from VDR-knockout mice. In addition, calcitriol
      activated Akt in cardiomyocytes and pretreatment with triciribine prevented the
      calcitriol-induced increase of outward K+ currents. In conclusion, we demonstrate
      that calcitriol via VDR and Akt increases both Itof and Ikur densities in mouse
      ventricular cardiomyocytes. Our findings may provide new mechanistics clues for
      the cardioprotective role of this hormone in the heart.

PMID- 30197606
TI  - Internet Game Overuse Is Associated With an Alteration of Fronto-Striatal
      Functional Connectivity During Reward Feedback Processing.
AB  - Internet gaming disorder is associated with abnormal reward processing in the
      reward circuit, which is known to interact with other brain regions during
      feedback learning. Kim et al. (1) observed that individuals with internet game
      overuse (IGO) exhibit altered behavior and neural activity for non-monetary
      reward, but not for monetary reward. Here, we extend our analysis of IGO to the
      functional connectivity of the reward network. Functional MRI data were obtained
      during a stimulus-response association learning task from 18 young males with IGO
      and 20 age-matched controls, where either monetary or non-monetary rewards were
      given as positive feedback for a correct response. Group differences in task
      dependent functional connectivity were examined for the ventromedial prefrontal
      cortex (vmPFC) and ventral striatum (VS), which are known for reward evaluation
      and hedonic response processing, respectively, using a generalized form of the
      psychophysiological interaction approach. For non-monetary reward processing, no
      differences in functional connectivity were found. In contrast, for monetary
      reward, connectivity of the vmPFC with the left caudate nucleus was weaker for
      the IGO group relative to controls, while vmPFC connectivity with the right
      nucleus accumbens (NAcc) was elevated. The strength of vmPFC-NAcc functional
      connectivity appeared to be behaviorally relevant, because individuals with
      stronger vmPFC-NAcc connectivity showed lower learning rates for monetary reward.
      In addition, the IGO group showed weaker ventral striatum functional connectivity
      with various brain regions, including the right ventrolateral prefrontal cortex,
      dorsal anterior cingulate regions, and left pallidum. Thus, for monetary reward,
      the IGO group exhibited stronger functional connectivity within the brain regions
      involved in motivational salience, whereas they showed reduced functional
      connectivity the widely distributed brain areas involved in learning or
      attention. These differences in functional connectivity of reward networks, along
      with related behavioral impairments of reward learning, suggest that internet
      gaming disorder is associated with the increased incentive salience or "wanting"
      of addiction disorders, and may serve as the neurobiological mechanisms
      underlying the impaired goal-directed behavior.

PMID- 30197607
TI  - The Experience of Sleep Problems and Their Treatment in Young People at Ultra
      High Risk of Psychosis: A Thematic Analysis.
AB  - We view sleep disruption as a contributory causal factor in the development of
      psychotic experiences. Clinical trials indicate that psychological interventions
      targeting insomnia result in improvements in both sleep and psychotic
      experiences. The aim of this study was to gain the perspective of young people at
      ultra-high risk of psychosis on their sleep problems and associated psychological
      treatment. Interviews were conducted with 11 patients, aged 15-22 years, at ultra
      high risk of psychosis who had received a psychological sleep intervention.
      Responses were analyzed using thematic analysis. Disrupted sleep timing and a
      lack of routine were the characteristic hallmarks of participants' sleep
      problems. Sleep disturbance, psychological wellbeing, and functioning had a
      reciprocal relationship. There were negative expectations prior to therapy,
      however meaningful improvements occurred in sleep, mood, and functioning. The
      active implementation of therapy techniques was highlighted as important. These
      findings indicate that the treatment of sleep problems is highly valued and has a
      meaningful impact on wellbeing in young people at ultra-high risk of psychosis.

PMID- 30197605
TI  - Long Non-coding RNA Structure and Function: Is There a Link?
AB  - RNA has emerged as the prime target for diagnostics, therapeutics and the
      development of personalized medicine. In particular, the non-coding RNAs (ncRNAs)
      that do not encode proteins, display remarkable biochemical versatility. They can
      fold into complex structures and interact with proteins, DNA and other RNAs,
      modulating the activity, DNA targets or partners of multiprotein complexes. Thus,
      ncRNAs confer regulatory plasticity and represent a new layer of epigenetic
      control that is dysregulated in disease. Intriguingly, for long non-coding RNAs
      (lncRNAs, >200 nucleotides length) structural conservation rather than nucleotide
      sequence conservation seems to be crucial for maintaining their function. LncRNAs
      tend to acquire complex secondary and tertiary structures and their functions
      only impose very subtle sequence constraints. In the present review we will
      discuss the biochemical assays that can be employed to determine the lncRNA
      structural configurations. The implications and challenges of linking function
      and lncRNA structure to design novel RNA therapeutic approaches will also be
      analyzed.

PMID- 30197609
TI  - Adapting the Research Development and Innovation (RD & I) Value Chain in
      Psychology to Educational Psychology Area.
AB  - Educational Psychology, as an area of Psychology that specializes in formative
      processes, faces several important challenges in the information and knowledge
      society of this twenty first century. One of these challenges is to facilitate a
      paradigm shift from a nearly exclusive focus on social science to the scientific
      technological approach of a discipline that produces innovation and meaningful
      transfer of science and technology. The Research, Development, and Innovation (RD
      & I) value chain means pursuing these three endeavors in both the academic and
      professional lines of Educational Psychology. It is a strategy of innovation that
      leads us to integrate academic or research activity (R), research-related or
      professional scientific-technological development of innovation (D) and transfer
      and entrepreneurship activity (I). Generating innovation and transfer, applicable
      to educational contexts, can be an important stimulus of activity for new
      practicing psychologists in Educational Psychology. The RD & I value chain can
      become an academic, research-related or professional advantage in different
      activities, since it pertains to the processes, products and services found in
      the sphere of Educational Psychology. Several examples of how the RD & I chain
      can help improve psychoeducational activities are presented. First, we analyze
      competitive improvements that the RD & I chain can offer in competitive bids.
      Second, we give examples of the RD & I chain in the development of new processes,
      products and services in Projects of Innovation and Entrepreneurship in
      Educational Psychology, specifically illustrating the chain in each case. In
      order for this conception to take shape, a new cross-functional area must be
      created in professional and educational organizations. Specifically, this means
      creating an RD & I Department, or some area that branches across the other
      functions. The mission of this cross-functional unit is the actual implementation
      of the RD & I chain in the educational organization, as well as an incentive for
      innovative activities: use of ICT applications, organizational improvement,
      improved assessment, analysis of information produced by the organization itself,
      cost-benefit analysis, strategic decision-making processes, and so on.

PMID- 30197608
TI  - The Double Burdens of Mental Health Among AIDS Patients With Fully Successful
      Immune Restoration: A Cross-Sectional Study of Anxiety and Depression in China.
AB  - Background: Anxiety and depression continue to be significant comorbidities for
      people with HIV infection. We investigated the prevalence of and factors
      associated with anxiety and depression among adult HIV-infected patients across
      China. Methods: In this cross-sectional study, we described clinical and
      psychosocial variables related to depression and anxiety in 4103 HIV-infected
      persons. Doctors assessed anxiety and depression by asking patients whether they
      had experienced anxiety or depression in the prior month. Patients also self
      administered the Hospital Anxiety and Depression (HAD) scale; those with score
      >=8 on HAD-A/D were considered to be at high risk of anxiety or depression.
      Results: Associations between socio-demographic, psychosocial, and ART-related
      clinical factors and risk of depression or anxiety were investigated using
      multivariable logistic regression. Among patients assessed between 9/2014 and
      11/2015, 27.4% had symptoms of anxiety, 32.9% had symptoms of depression, and
      19.0% had both. Recentness of HIV diagnoses (P = 0.046) was associated with
      elevated odds of anxiety. Older age (P = 0.004), higher educational attainment (P
      < 0.001), employment (P = 0.001), support from family / friends (P < 0.001), and
      sleep disturbance (P < 0.001), and number of ART regimen switches (P = 0.046)
      were associated with risk of depression, while neither sex nor transmission route
      showed any associations. There were no significant associations with HIV-specific
      clinical factors including current CD4+ T cell count and current viral load.
      Conclusions: Prevalence of symptoms of anxiety and depression is high in this
      cohort of treatment-experienced HIV patients. Psychological and social
      demographic factors, rather than HIV disease status, were associated with risk of
      depression and anxiety. This finding highlights the need to deliver interventions
      to address the mental health issues affecting HIV-infected persons with fully
      successful immune restoration across China.

PMID- 30197610
TI  - Time Perspective Biases Are Associated With Poor Sleep Quality, Daytime
      Sleepiness, and Lower Levels of Subjective Well-Being Among Older Adults.
AB  - This study examined the extent to which individual differences in time
      perspective, i.e., habitual way of relating to the personal past, present, and
      future, are associated with sleep quality and daytime sleepiness in a sample of
      older adults. The participants (N = 437, 60-90 years) completed the Karolinska
      Sleep Questionnaire (KSQ), a the Swedish version of the Zimbardo Time Perspective
      Inventory (S-ZTPI), and two ratings of subjective well-being (SWB) (life
      satisfaction, happiness). Based on established relationships between dimension of
      time perspective and other variables (e.g., depression) and relations between
      negative retrospection (rumination) and negative prospection (worry) in prior
      studies, we expected higher scores on Past Negative and Future Negative to be
      linked to poor sleep quality and (indirectly) increased daytime sleepiness.
      Moreover, we examined the possibility that variations in perceived sleep and
      sleepiness during the day mediates the expected association between an aggregate
      measure of deviations from a so called balanced time perspective (DBTP) and SWB.
      In regression analyses controlling for demographic factors (age, sex, and work
      status), higher scores on Past Negative and Future Negative predicted poorer
      sleep quality and higher levels of daytime sleepiness. Additionally, most of the
      association between time perspective and daytime sleepiness was accounted for by
      individual differences in sleep quality. Finally, structural equation modeling
      yielded results consistent with the hypothesis that variations in sleep mediate
      part of the negative relationship between DBTP and SWB. Given that good sleep is
      essential to multiple aspects of health, future studies evaluating relationships
      between time perspective and adverse health outcomes should consider sleep
      quality as a potentially contributing factor.

PMID- 30197611
TI  - Expertise in Evaluating Choreographic Creativity: An Online Variation of the
      Consensual Assessment Technique.
AB  - In contemporary dance, experts evaluate creativity in competitions, auditions,
      and performances, typically through ratings of choreography or improvisation.
      Audiences also implicitly evaluate choreographic creativity, so dancers'
      livelihoods also hinge upon the opinions of non-expert observers. However, some
      argue that the abstract and often pedestrian nature of contemporary dance
      confuses non-expert audiences. Therefore, agreement regarding creativity and
      appreciation amongst experts and non-experts may be low. Finding appropriate
      methodologies for reliable and real-world creativity evaluation remains the
      subject of considerable debate within the psychology creativity research field.
      Although considerably variant in methodological operationalisation, the
      Consensual Assessment Technique (CAT) asks individuals to use an implicit
      definition to assess creativity in others' work. This study aimed to investigate
      the role of experience and expertise in the evaluation of choreographic
      creativity, with a secondary aim of testing the feasibility of an online
      snowballing methodology for large-scale dance-specific research, informed by the
      methodology of the CAT. We filmed 23 Contemporary Dance students each performing
      a 3-min peer-choreographed solo and then recruited 850 online evaluators with
      varying degrees of expertise and experience in dance and creativity. Evaluators
      viewed at least one randomly selected video and rated creativity, technical
      ability, appreciation and understanding of the work, each using a seven-point
      Likert scale. A one-way ANOVA showed a significant difference in creativity
      ratings across the 23 videos, and creativity correlated significantly with the
      other variables. We then categorized evaluators on nine aspects of their dance
      and creative experience and entered the data into a repeated-measures linear
      mixed model. Two of the fixed effects yielded differences in creativity
      evaluations: (i) contemporary choreographic experience and (ii) self-reported
      creative expertise, as did the random effect of the video. The results indicate
      that personal experience of the choreographic process impacts creativity
      assessment, above and beyond experience in dance class participation.
      Implications for creativity assessment within creativity research and practice
      are discussed.

PMID- 30197612
TI  - Effective Treatment of Veterans With PTSD: Comparison Between Intensive Daily and
      Weekly EMDR Approaches.
AB  - The effectiveness of EMDR therapy in treating veterans diagnosed with PTSD was
      evaluated in this study using two treatment formats: intensive daily EMDR
      treatment provided twice a day during a 10-day period and a second format of one
      session each week. The study used archived outcome data previously collected and
      stored at Soldier Center. Both formats provided 18-20 treatment sessions of EMDR
      therapy to veterans diagnosed with PTSD that included dissociative exhibitions
      and moral injury issues. Questions addressed included: (1) does EMDR therapy
      administered twice daily ameliorate veterans' PTSD symptoms; (2) does EMDR
      therapy administered twice daily provide equivalent outcome results as EMDR
      therapy administered weekly for 18-20 sessions; and (3) does the treatment
      outcome persist. The effectiveness of the weekly treatment group was also
      evaluated. Both groups' results were assessed at pre-treatment, post-treatment
      and 1-year follow-up. The results indicated that both weekly treatment and
      intensive daily treatment groups produced statistically significant treatment
      effects (p < 0.001) that were maintained at 1-year follow-up. The10-day EMDR
      intensive daily treatment (EMDR therapy twice a day for 10 days) produced a
      similar outcome as to that of the weekly treatment with a 1-year follow-up.
      Results support the effectiveness of EMDR therapy when offered in both weekly
      treatment format as well as the intensive 10-day format on an outpatient basis.
      While recognizing the limitations of this study the results are significant to
      warrant additional research.

PMID- 30197614
TI  - Culture Moderates the Relationship Between Emotional Fit and Collective Aspects
      of Well-Being.
AB  - The present study examined how emotional fit with culture - the degree of
      similarity between an individual' emotional response to the emotional response of
      others from the same culture - relates to well-being in a sample of Asian
      American and European American college students. Using a profile correlation
      method, we calculated three types of emotional fit based on self-reported
      emotions, facial expressions, and physiological responses. We then examined the
      relationships between emotional fit and individual well-being (depression, life
      satisfaction) as well as collective aspects of well-being, namely collective self
      esteem (one's evaluation of one's cultural group) and identification with one's
      group. The results revealed that self-report emotional fit was associated with
      greater individual well-being across cultures. In contrast, culture moderated the
      relationship between self-report emotional fit and collective self-esteem, such
      that emotional fit predicted greater collective self-esteem in Asian Americans,
      but not in European Americans. Behavioral emotional fit was unrelated to well
      being. There was a marginally significant cultural moderation in the relationship
      between physiological emotional fit in a strong emotional situation and group
      identification. Specifically, physiological emotional fit predicted greater group
      identification in Asian Americans, but not in European Americans. However, this
      finding disappeared after a Bonferroni correction. The current finding extends
      previous research by showing that, while emotional fit may be closely related to
      individual aspects of well-being across cultures, the influence of emotional fit
      on collective aspects of well-being may be unique to cultures that emphasize
      interdependence and social harmony, and thus being in alignment with other
      members of the group.

PMID- 30197615
TI  - The Origin of Protoconversation: An Examination of Caregiver Responses to Cry and
      Speech-Like Vocalizations.
AB  - Turn-taking is a universal and fundamental feature of human vocal communication.
      Through protoconversation, caregivers play a key role for infants in helping them
      learn the turn-taking system. Infants produce both speech-like vocalizations
      (i.e., protophones) and cries from birth. Prior research has shown that
      caregivers take turns with infant protophones. However, no prior research has
      investigated the timing of caregiver responses to cries. The present work is the
      first to systematically investigate different temporal patterns of caregiver
      responses to protophones and to cries. Results showed that, even in infants'
      first 3 months of life, caregivers were more likely to take turns with
      protophones and to overlap with cries. The study provides evidence that
      caregivers are intuitively aware that protophones and cries are functionally
      different: protophones are treated as precursors to speech, whereas cries are
      treated as expressions of distress.

PMID- 30197613
TI  - Associative Learning of Stimuli Paired and Unpaired With Reinforcement:
      Evaluating Evidence From Maggots, Flies, Bees, and Rats.
AB  - Finding rewards and avoiding punishments are powerful goals of behavior. To
      maximize reward and minimize punishment, it is beneficial to learn about the
      stimuli that predict their occurrence, and decades of research have provided
      insight into the brain processes underlying such associative reinforcement
      learning. In addition, it is well known in experimental psychology, yet often
      unacknowledged in neighboring scientific disciplines, that subjects also learn
      about the stimuli that predict the absence of reinforcement. Here we evaluate
      evidence for both these learning processes. We focus on two study cases that both
      provide a baseline level of behavior against which the effects of associative
      learning can be assessed. Firstly, we report pertinent evidence from Drosophila
      larvae. A re-analysis of the literature reveals that through paired presentations
      of an odor A and a sugar reward (A+) the animals learn that the reward can be
      found where the odor is, and therefore show an above-baseline preference for the
      odor. In contrast, through unpaired training (A/+) the animals learn that the
      reward can be found precisely where the odor is not, and accordingly these larvae
      show a below-baseline preference for it (the same is the case, with inverted
      signs, for learning through taste punishment). In addition, we present previously
      unpublished data demonstrating that also during a two-odor, differential
      conditioning protocol (A+/B) both these learning processes take place in larvae,
      i.e., learning about both the rewarded stimulus A and the non-rewarded stimulus B
      (again, this is likewise the case for differential conditioning with taste
      punishment). Secondly, after briefly discussing published evidence from adult
      Drosophila, honeybees, and rats, we report an unpublished data set showing that
      relative to baseline behavior after truly random presentations of a visual
      stimulus A and punishment, rats exhibit memories of opposite valence upon paired
      and unpaired training. Collectively, the evidence conforms to classical findings
      in experimental psychology and suggests that across species animals associatively
      learn both through paired and through unpaired presentations of stimuli with
      reinforcement - with opposite valence. While the brain mechanisms of unpaired
      learning for the most part still need to be uncovered, the immediate implication
      is that using unpaired procedures as a mnemonically neutral control for
      associative reinforcement learning may be leading analyses astray.

PMID- 30197616
TI  - Bimodal Patterning Discrimination in Harnessed Honey Bees.
AB  - In natural environments, stimuli and events learned by animals usually occur in a
      combination of more than one sensory modality. An important problem in
      experimental psychology has been thus to understand how organisms learn about
      multimodal compounds and how they discriminate this compounds from their unimodal
      constituents. Here we tested the ability of honey bees to learn bimodal
      patterning discriminations in which a visual-olfactory compound (AB) should be
      differentiated from its visual (A) and olfactory (B) elements. We found that
      harnessed bees trained in classical conditioning of the proboscis extension
      reflex (PER) are able to solve bimodal positive and negative patterning (NP)
      tasks. In positive patterning (PP), bees learned to respond significantly more to
      a bimodal reinforced compound (AB+) than to non-reinforced presentations of
      single visual (A-) or olfactory (B-) elements. In NP, bees learned to suppress
      their responses to a non-reinforced compound (AB-) and increase their responses
      to reinforced presentations of visual (A+) or olfactory (B+) elements alone. We
      compared the effect of two different inter-trial intervals (ITI) in our
      conditioning approaches. Whereas an ITI of 8 min allowed solving both PP and NP,
      only PP could be solved with a shorter ITI of 3 min. In all successful cases of
      bimodal PP and NP, bees were still able to discriminate between reinforced and
      non-reinforced stimuli in memory tests performed one hour after conditioning. The
      analysis of individual performances in PP and NP revealed that different learning
      strategies emerged in distinct individuals. Both in PP and NP, high levels of
      generalization were found between elements and compound at the individual level,
      suggesting a similar difficulty for bees to solve these bimodal patterning tasks.
      We discuss our results in light of elemental and configural learning theories
      that may support the strategies adopted by honey bees to solve bimodal PP or NP
      discriminations.

PMID- 30197617
TI  - The Mind-Evolution Problem: The Difficulty of Fitting Consciousness in an
      Evolutionary Framework.

PMID- 30197618
TI  - Heterogeneity in Cognitive and Socio-Emotional Functioning in Adolescents With On
      Track and Delayed School Progression.
AB  - Adolescence is characterized by considerable changes in cognitive and socio
      emotional skills. There are considerable differences between adolescents with
      regards to the development of these skills. However, most studies examine
      adolescents' average functioning, without taking into account this heterogeneity.
      The current study applies network analysis in order to examine heterogeneity of
      cognitive and socio-emotional functioning in adolescents on-track or delayed in
      their school progression. Data was collected at two time-points for on-track (n =
      320) and delayed (n = 69) adolescents (Mage = 13.30 years, SDage = 0.77).
      Repeated measures ANOVA showed no significant differences between the groups in
      cognitive and socio-emotional functioning (p's > 0.05). Network analysis revealed
      that executive functions play a key role in the network of cognitive, social, and
      emotional functioning. This is especially the case in the delayed group where
      executive functions are even more central, both at T1 (inhibition and shifting)
      and T2 (shifting). Subsequent community analysis revealed three profiles in both
      groups: a well-adapted and well-balanced group, a group with high levels of need
      for arousal and risk-taking, and a group with regulation problems. Compared to on
      track adolescents, delayed adolescents showed even higher levels of risk-taking
      in the second profile and higher levels of executive function problems in the
      third profile at T1. These differences were leveled out at T2, indicating
      adolescents in the delayed group catch up with their peers. This study highlights
      the intricate balance between cognitive, social and emotional functioning in
      adolescents in relation to school performance and provides preliminary evidence
      of the importance of taking individual differences within groups into account.

PMID- 30197619
TI  - Subclinically Anxious Adolescents Do Not Display Attention Biases When Processing
      Emotional Faces - An Eye-Tracking Study.
AB  - Recent research suggests that early difficulties with emotion regulation go along
      with an increased risk for developing psychiatric disorders, such as anxiety
      disorders for example. Adolescent anxiety is often referred to as a gateway
      disorder, due to its high predictability for lifelong persistent mental health
      problems. It has been shown that clinically anxious adolescents exhibit attention
      biases toward negative stimuli, yet whether these biases can also be found in the
      subclinical range of subclinically anxious adolescents is currently unclear. In
      this study, we set out to investigate this question by combining an emotional Go
      Nogo task with eye-tracking techniques to assess attention biases for emotional
      faces in a subclinical sample of 23 subclinically anxious adolescent girls. This
      combined approach allowed us to look at both, behavioral and covert attention
      biases. Using both traditional and Bayesian hypothesis testing, we found no
      evidence for a bias toward negative, threat-relevant stimuli in the behavioral
      level or eye-tracking data. We believe that the results can help close a gap in
      the current literature by showing that like low-anxious adolescents,
      subclinically anxious adolescents do not exhibit attention biases when viewing de
      contextualized emotional stimuli in the Overlap task. Together with previous
      research findings in clinically anxious participants which have reported high
      levels of attention biases, our results seem to suggest that attention biases do
      no increase linearly as a function of individual anxiety level. Future research
      is now needed to explore the contribution of additional factors, such as
      depression for example.

PMID- 30197622
TI  - Physical Activity and Sleep/Wake Behavior, Anthropometric, and Metabolic Profile
      in Pediatric Narcolepsy Type 1.
AB  - Objectives: Regular physical activity is routinely recommended in children and
      adolescents suffering from narcolepsy type 1 (NT1), but controlled studies
      analyzing its influence on sleep/wake behavior, metabolic, and anthropometric
      profile in pediatric NT1 are lacking. Methods: Fifty consecutive drug-naive NT1
      children and adolescents were assessed through actigraphic, clinical, and
      metabolic evaluations. Patients were compared with respect to their engagement in
      leisure-time physical activities (LTPA): patients engaged in LTPA (n = 30) and
      patients not engaged (No-LTPA, n = 20), respectively. Results: LTPA patients
      presented lower BMI, with different BMI categories distribution and higher HDL
      cholesterol, when compared with No-LTPA subjects. Increased night-sleep duration,
      higher sleep quality, and reduction of nap frequency were documented through
      actigraphy in LTPA subjects. Subjective sleepiness, as measured by ESS-CHAD, was
      also lower in LTPA subjects while cataplexy frequency proved similar between the
      two groups. Discussion: In pediatric NT1 patients, regular engagement in LTPA is
      associated with significant differences on sleepiness, anthropometric and
      metabolic profile and objectively assessed sleep/wake behavior. Engagement in
      LTPA is beneficial and should be strongly encouraged in pediatric NT1 patients.

PMID- 30197621
TI  - Cerebral White Matter Changes in Young Healthy Individuals With High Trait
      Anxiety: A Tract-Based Spatial Statistics Study.
AB  - Background: Abnormalities in prespecified and empirical white matter tracts in
      young patients with anxiety-related disorders have been reported in some
      diffusion tensor imaging (DTI) studies. However, with few literatures examining
      the association between the integrity of whole brain white matter and trait
      anxiety levels in the non-clinical populations, whether white matter changes
      arise in young healthy individuals with high trait anxiety remains unknown.
      Methods: We examined whole brain white matter alterations in young healthy
      individuals with high anxiety but without history of neurological or psychiatric
      disorders via DTI technology. Group comparison of tract-based spatial statistics
      (TBSS) was performed to investigate the microstructural diffusion alterations in
      38 high anxious subjects in comparison with 34 low anxious subjects matched with
      age, gender, and degree of education. These analyses controlled for depression to
      establish specificity to trait anxiety. Results: Young healthy subjects with high
      trait anxiety had significantly decreased fractional anisotropy (FA) values in
      multiple clusters, including corona radiate (CR), anterior thalamic radiation
      (ATR), inferior fronto-occipital fasciculus (IFOF), bilaterally, body, genu, and
      splenium of corpus callosum (CC) and forceps minor, compared with low trait
      anxious subjects. For the abnormal FA regions, the other diffusion metrics were
      also altered slightly. Conclusions: Non-clinical individuals with high anxiety
      already have white matter alterations in the thalamus-cortical circuit and some
      emotion-related areas that were widely reported in anxiety-related disorders. The
      altered white matter may be a vulnerability marker in individuals at high risk of
      clinical anxiety. These findings can deepen our understanding of the pathological
      mechanism of anxiety and further support the need for preventive interventions in
      high anxiety individuals.

PMID- 30197620
TI  - Endocrine Crosstalk Between Skeletal Muscle and the Brain.
AB  - Skeletal muscle is an essential regulator of energy homeostasis and a potent
      coordinator of exercise-induced adaptations in other organs including the liver,
      fat or the brain. Skeletal muscle-initiated crosstalk with other tissues is
      accomplished though the secretion of myokines, protein hormones which can exert
      autocrine, paracrine and long-distance endocrine effects. In addition, the
      enhanced release or uptake of metabolites from and into contracting muscle cells,
      respectively, likewise can act as a powerful mediator of tissue interactions, in
      particular in regard to the central nervous system. The present review will
      discuss the current stage of knowledge regarding how exercise and the muscle
      secretome improve a broad range of brain functions related to vascularization,
      neuroplasticity, memory, sleep and mood. Even though the molecular and cellular
      mechanisms underlying the communication between muscle and brain is still poorly
      understood, physical activity represents one of the most effective strategies to
      reduce the prevalence and incidence of depression, cognitive, metabolic or
      degenerative neuronal disorders, and thus warrants further study.

PMID- 30197625
TI  - Improved Thyroid Hypoechogenicity Following Bariatric-Induced Weight Loss in
      Euthyroid Adults With Severe Obesity-a Pilot Study.
AB  - Background: Obesity may affect both biochemical thyroid function tests; and
      thyroid morphology, as assessed using ultrasound scans (US). The aim of the
      present pilot study was to explore whether weight loss achieved by bariatric
      surgery alters thyroid US morphology including gray-scale measurements; and/or
      function in euthyroid adults with severe obesity. Methods: Euthyroid adults (>18
      years) with body mass index (BMI) >=40 kg/m2 and negative thyroid peroxidase
      antibodies were assessed at baseline (pre-surgery) and after achieving at least
      5% weight loss of their baseline body weight following bariatric surgery.
      Anthropometric assessments, biochemical/hormonal measurements (TSH, free-T4, free
      T3, reverse-T3, and leptin) and thyroid US with gray-scale histogram analysis
      were performed at the baseline and post-surgery follow-up. Results: Ten
      Caucasian, euthyroid patients (women/men: 8/2; age: 48.6 +/- 3.1 years; BMI: 51.4
      +/- 1.8 kg/m2) successfully completed this study with significantly decreased
      body weight (>5% weight loss), waist circumference and serum leptin levels post
      surgery (mean post-surgery follow-up duration: 16.5 +/- 2.5 months). In parallel
      to the observed bariatric-induced weight loss, thyroid US echogenicity increased
      by 25% (p = 0.03), without significant changes in thyroid volume. No significant
      changes in thyroid function tests were detected. No significant correlations were
      observed between the increase in thyroid echogenicity and the decreases in
      anthropometric parameters and circulating leptin. Conclusion: Our results
      indicate that in euthyroid adults with severe obesity, marked weight loss
      achieved by bariatric surgery is associated with a parallel significant increase
      in the thyroid US echogenicity, suggesting that morphological changes of the
      thyroid in obesity are reversible with weight loss. Clinical Trial Registration:
      www.ClinicalTrials.gov, identifier: NCT03048708.

PMID- 30197623
TI  - Heparan Sulfate and Heparan Sulfate Proteoglycans in Cancer Initiation and
      Progression.
AB  - Heparan sulfate (HS) are complex unbranched carbohydrate chains that are heavily
      modified by sulfate and exist either conjugated to proteins or as free,
      unconjugated chains. Proteins with covalently bound Heparan sulfate chains are
      termed Heparan Sulfate Proteoglycans (HSPGs). Both HS and HSPGs bind to various
      growth factors and act as co-receptors for different cell surface receptors. They
      also modulate the dynamics and kinetics of various ligand-receptor interactions,
      which in turn can influence the duration and potency of the signaling. HS and
      HSPGs have also been shown to exert a structural role as a component of the
      extracellular matrix, thereby altering processes such as cell adhesion, immune
      cell infiltration and angiogenesis. Previous studies have shown that HS are
      deregulated in a variety of solid tumors and hematological malignancies and
      regulate key aspects of cancer initiation and progression. HS deregulation in
      cancer can occur as a result of changes in the level of HSPGs or due to changes
      in the levels of HS biosynthesis and remodeling enzymes. Here, we describe the
      major cell-autonomous (proliferation, apoptosis/senescence and differentiation)
      and cell-non-autonomous (angiogenesis, immune evasion, and matrix remodeling)
      roles of HS and HSPGs in cancer. Finally, we discuss therapeutic opportunities
      for targeting deregulated HS biosynthesis and HSPGs as a strategy for cancer
      treatment.

PMID- 30197624
TI  - Pathogenesis of Nonalcoholic Steatohepatitis and Hormone-Based Therapeutic
      Approaches.
AB  - Non-alcoholic fatty liver disease (NAFLD) is an emerging global health problem
      and a potential risk factor for type 2 diabetes, cardiovascular disease, and
      chronic kidney disease. Nonalcoholic steatohepatitis (NASH), an advanced form of
      NAFLD, is a predisposing factor for development of cirrhosis and hepatocellular
      carcinoma. The increasing prevalence of NASH emphasizes the need for novel
      therapeutic approaches. Although therapeutic drugs against NASH are not yet
      available, fundamental insights into the pathogenesis of NASH have been made
      during the past few decades. Multiple therapeutic strategies have been developed
      and are currently being explored in clinical trials or preclinical testing. The
      pathogenesis of NASH involves multiple intracellular/extracellular events in
      various cell types in the liver or crosstalk events between the liver and other
      organs. Here, we review current findings and knowledge regarding the pathogenesis
      of NASH, focusing on the most recent advances. We also highlight hormone-based
      therapeutic approaches for treatment of NASH.

PMID- 30197626
TI  - An Adipokinetic Hormone Acts as a Volume Regulator in the Intertidal Gastropod
      Mollusk, Aplysia californica.
AB  - Adipokinetic hormone (AKH) is a multifunctional neuropeptide in the gonadotropin
      releasing hormone superfamily. In insects, AKH acts to mobilize energy stores
      during times of high energetic demand, but has been shown to have other effects.
      In lophotrochozoans, the presence and function of AKH are less characterized. We
      have previously identified an AKH in an intertidal gastropod mollusk, the
      California sea hare (Aplysia californica), and named it ac-AKH. Our previous data
      showed ac-AKH induced an acute weight loss, suggesting a role in volume
      regulation. The overarching goals of this study were to test the role of ac-AKH
      as a volume regulator and examine the mechanism by which ac-AKH induced the acute
      weight loss. Our results showed that ac-AKH reduced body mass, in part, through
      the reduction of hemolymph volume without altering hemolymph osmolality or
      specific osmolytes. The effect of ac-AKH on volume loss was accentuated under a
      hyposaline condition. We further showed that ac-akh expression was inhibited
      during a hyposaline challenge, and that the administration of ac-AKH partially
      reversed the increase in body mass, but not hemolymph osmolality change, caused
      by the hyposaline challenge. These data collectively show that ac-AKH is a
      proximate regulator controlling the fluid volume, but not osmolality, in A.
      californica. Importantly, our results highlight the functional divergence of this
      structurally conserved neuropeptide in the molluscan lineage.

PMID- 30197627
TI  - Central Precocious Puberty in a Child With Metachromatic Leukodystrophy.
AB  - Metachromatic leucodystrophy (MLD) is a rare inherited lysosomal disorder caused
      by reduced activity of the enzyme arylsulfatase A with accumulation of sulfatides
      in the nervous system. We report a female child affected by MLD who developed
      central precocious puberty (CPP). This association has not been described so far.
      The proposita, after normal growth and psychomotor development, at age of 30
      months presented with a rapidly progressive gait disturbance with frequent falls
      and with loss of acquired language skills. Magnetic resonance imaging showed
      leukoencephalopathy. Biochemical blood essays showed a 91% reduction in the
      arylsulfatase A activity and genetic analysis revealed compound heterozygous
      mutations of the Arylsulfatase A gene, enabling diagnosis of MLD. Subsequently,
      the patient had further rapid deterioration of motor and cognitive functions and
      developed drug-resistant epilepsy. At 4 years and 7 months of age bilateral
      thelarche occurred. Magnetic resonance imaging showed a small pituitary gland,
      extensive signal changes of the brain white matter, increased choline, decreased
      N-acetyl-aspartate and presence of lactate on 1HMR spectroscopy. Pelvic
      ultrasound demonstrated a slightly augmented uterine longitudinal diameter (42
      mm). The gonadotropin-releasing hormone stimulation test revealed a pubertal LH
      peak of 12.9 UI/l. A diagnosis of CPP was made and treatment with gonadotropin
      releasing hormone agonists was initiated, with good response. In conclusion, a
      CPP may occur in MLD as in other metabolic diseases with white matter
      involvement. We hypothesize that brain accumulation of sulfatides could have
      interfered with the complex network regulating with the hypothalamic-pituitary
      axis and thus triggering CPP in our patient.

PMID- 30197629
TI  - Pockets of HIV Non-infection Within Highly-Infected Risk Networks in Athens,
      Greece.
AB  - As part of a network study of HIV infection among people who inject drugs (PWID)
      and their contacts, we discovered a connected subcomponent of 29 uninfected PWID.
      In the context of a just-declining large epidemic outbreak, this raised a
      question: What explains the existence of large pockets of uninfected people?
      Possible explanations include "firewall effects" (Friedman et al., 2000;
      Dombrowski et al., 2017) wherein the only HIV+ people that the uninfected take
      risks with have low viral loads; "bottleneck effects" wherein few network paths
      into the pocket of non-infection exist; low levels of risk behavior; and an
      impending outbreak. We considered each of these. Participants provided
      information on their enhanced sexual and injection networks and assisted us in
      recruiting network members. The largest connected component had 241 members. Data
      on risk behaviors in the last 6 months were collected at the individual level.
      Recent infection was determined by LAg (SediaTM Biosciences Corporation), data on
      recent seronegative tests, and viral load. HIV RNA was quantified using Artus HI
      Virus-1 RG RT-PCR (Qiagen). The 29 members of the connected subcomponent of
      uninfected participants were connected (network distance = 1) to 17 recently
      infected and 24 long-term infected participants. Fourteen (48%) of these 29
      uninfected were classified as "extremely high risk" because they self-reported
      syringe sharing and had at least one injection partner with viral load >100,000
      copies/mL who also reported syringe sharing. Seventeen of the 29 uninfected were
      re-interviewed after 6 months, but none had seroconverted. These findings show
      the power of network research in discovering infection patterns that standard
      individual-level studies cannot. Theoretical development and exploratory network
      research studies may be needed to understand these findings and deepen our
      understanding of how HIV does and does not spread through communities. Finally,
      the methods developed here provide practical tools to study "bottleneck" and
      "firewall" network hypotheses in practice.

PMID- 30197628
TI  - Fermented Foods as a Dietary Source of Live Organisms.
AB  - The popularity of fermented foods and beverages is due to their enhanced shelf
      life, safety, functionality, sensory, and nutritional properties. The latter
      includes the presence of bioactive molecules, vitamins, and other constituents
      with increased availability due to the process of fermentation. Many fermented
      foods also contain live microorganisms that may improve gastrointestinal health
      and provide other health benefits, including lowering the risk of type two
      diabetes and cardiovascular diseases. The number of organisms in fermented foods
      can vary significantly, depending on how products were manufactured and
      processed, as well as conditions and duration of storage. In this review, we
      surveyed published studies in which lactic acid and other relevant bacteria were
      enumerated from the most commonly consumed fermented foods, including cultured
      dairy products, cheese, fermented sausage, fermented vegetables, soy-fermented
      foods, and fermented cereal products. Most of the reported data were based on
      retail food samples, rather than experimentally produced products made on a
      laboratory scale. Results indicated that many of these fermented foods contained
      105-7 lactic acid bacteria per mL or gram, although there was considerable
      variation based on geographical region and sampling time. In general, cultured
      dairy products consistently contained higher levels, up to 109/mL or g. Although
      few specific recommendations and claim legislations for what constitutes a
      relevant dose exist, the findings from this survey revealed that many fermented
      foods are a good source of live lactic acid bacteria, including species that
      reportedly provide human health benefits.

PMID- 30197630
TI  - A Prospective Study on the Fermentation Landscape of Gaseous Substrates to
      Biorenewables Using Methanosarcina acetivorans Metabolic Model.
AB  - The abundance of methane in shale gas and of other gases such as carbon monoxide,
      hydrogen, and carbon dioxide as chemical process byproducts has motivated the use
      of gas fermentation for bioproduction. Recent advances in metabolic engineering
      and synthetic biology allow for engineering of microbes metabolizing a variety of
      chemicals including gaseous feeds into a number of biorenewables and
      transportation liquid fuels. New computational tools enable the systematic
      exploration of all feasible conversion alternatives. Here we computationally
      assessed all thermodynamically feasible ways of co-utilizing CH4, CO, and CO2
      using ferric as terminal electron acceptor for the production of all key
      precursor metabolites. We identified the thermodynamically feasible co
      utilization ratio ranges of CH4, CO, and CO2 toward production of the target
      metabolite(s) as a function of ferric uptake. A revised version of the iMAC868
      genome-scale metabolic model of Methanosarcina acetivorans was chosen to assess
      co-utilization of CH4, CO, and CO2 and their conversion into selected target
      products using the optStoic pathway design tool. This revised version contains
      the latest information on electron flow mechanisms by the methanogen while
      supplied with methane as the sole carbon source. The interplay between different
      gas co-utilization ratios and the energetics of reverse methanogenesis were also
      analyzed using the same metabolic model.

PMID- 30197631
TI  - Fecal Microbiota Transplantation Ameliorates Experimentally Induced Colitis in
      Mice by Upregulating AhR.
AB  - Ulcerative colitis (UC) is a chronic non-specific inflammatory disease that
      occurs in the colon and rectum. While fecal microbiota transplantation (FMT) is
      gaining attention as a clinical treatment of UC, the molecular mechanisms behind
      this effect have yet to be fully understood. A C57BL/6 mouse model was
      established to test whether FMT promotes the recovery of colon inflammation.
      Administration of 2% dextran sulfate sodium (DSS) for 7 days successfully induced
      acute colitis, as evidenced by diarrhea, hematochezia and colon shortening as
      well as a decrease in body weight. FMT alleviated the severity of colon mucosa
      injury and improved histological alterations compared with that of the DSS group.
      In addition, FMT promoted homeostasis of the intestinal microbiota. Furthermore,
      FMT upregulated the expression of aryl hydrocarbon receptor (AHR), interleukin-10
      (IL-10), and transforming growth factor beta (TGF-beta) in colon tissues. These
      results suggest that the significant anti-inflammatory effect of FMT may be
      attributed to its promotion of IL-10 and TGF-beta production and AHR activation.
      Based on these results, FMT had a favorable therapeutic effect on DSS-induced
      colitis.

PMID- 30197632
TI  - Probiotic Lactobacillus plantarum Promotes Intestinal Barrier Function by
      Strengthening the Epithelium and Modulating Gut Microbiota.
AB  - Weaning disturbs the intestinal barrier function and increases the risk of
      infection in piglets. Probiotics exert beneficial health effects, mainly by
      reinforcing the intestinal epithelium and modulating the gut microbiota. However,
      the mechanisms of action, and especially, the specific regulatory effects of
      modulated microbiota by probiotics on the intestinal epithelium have not yet been
      elucidated. The present study aimed to decipher the protective effects of the
      probiotic Lactobacillus plantarum strain ZLP001 on the intestinal epithelium and
      microbiota as well as the effects of modulated microbiota on epithelial function.
      Paracellular permeability was measured with fluorescein isothiocyanate-dextran
      (FD-4). Gene and protein expression levels of tight junction (TJ) proteins,
      proinflammatory cytokines, and host defense peptides were determined by RT-qPCR,
      ELISA, and western blot analysis. Short-chain fatty acid (SCFA) concentrations
      were measured by ion chromatography. Fecal microbiota composition was assessed by
      high-throughput sequencing. The results showed that pretreatment with 108 colony
      forming units (CFU) mL-1 of L. plantarum ZLP001 significantly counteracted the
      increase in gut permeability to FD-4 induced by 106 CFU mL-1 enterotoxigenic
      Escherichia coli (ETEC). In addition, L. plantarum ZLP001 pretreatment alleviated
      the reduction in TJ proteins (claudin-1, occludin, and ZO-1) and downregulated
      proinflammatory cytokines IL-6 and IL-8, and TNFalpha expression and secretion
      caused by ETEC. L. plantarum ZLP001 also significantly increased the expression
      of the host defense peptides pBD2 and PG1-5 and pBD2 secretion relative to the
      control. Furthermore, L. plantarum ZLP001 treatment affected piglet fecal
      microbiota. The abundance of butyrate-producing bacteria Anaerotruncus and
      Faecalibacterium was significantly increased in L. plantarum ZLP001-treated
      piglets, and showed a positive correlation with fecal butyric and acetic acid
      concentrations. In addition, the cell density of Clostridium sensu stricto 1,
      which may cause epithelial inflammation, was decreased after L. plantarum ZLP001
      administration, while the beneficial Lactobacillus was significantly increased.
      Our findings suggest that L. plantarum ZLP001 fortifies the intestinal barrier by
      strengthening epithelial defense functions and modulating gut microbiota.

PMID- 30197633
TI  - Antagonistic Activities and Probiotic Potential of Lactic Acid Bacteria Derived
      From a Plant-Based Fermented Food.
AB  - In this study, antagonistic activities and probiotic potential of lactic acid
      bacteria (LAB) derived from a plant-based fermented food, kimchi, were
      demonstrated. The cell free supernatants (CFS) from Lactobacillus curvatus KCCM
      43119, Leuconostoc mesenteroides KCCM 43060, Weissella cibaria KCTC 3746, and W.
      koreensis KCCM 41517 completely inhibited the growth of foodborne pathogenic
      bacteria, while neutralized CFS (pH 6.5) partially inhibited the growth. The
      competition, exclusion, and displacement of foodborne pathogenic bacteria by the
      LAB strains from adhesion to HT-29 cells were investigated. The LAB strains were
      able to compete with, exclude, and displace the foodborne pathogenic bacteria.
      However, the degree of inhibition due to the adhesion was found to be a LAB
      strain-dependent phenomenon. The LAB strains showed high coaggregation with
      foodborne pathogenic bacteria, and they also exhibited high resistance to acidic
      condition. Except W. cibaria KCTC 3746, all LAB strains were capable of surviving
      in the presence of bile salts. Furthermore, while all LAB strains were resistant
      to chloramphenicol, kanamycin, streptomycin, gentamicin, and erythromycin, only
      W. cibaria KCTC 3746 and W. koreensis KCCM 41517 displayed resistance to
      vancomycin. These results suggest that the LAB strains derived from kimchi
      exerted antagonistic activities against foodborne pathogenic bacteria with
      probiotic potential.

PMID- 30197635
TI  - Metabolic Syndrome During Perinatal Period in Sows and the Link With Gut
      Microbiota and Metabolites.
AB  - In humans, the metabolic and immune changes occurring during perinatal period
      also describe metabolic syndrome. Gut microbiota can cause symptoms of metabolic
      syndrome in pregnant women. Increased gut permeability is also involved in
      metabolic disorders in non-pregnant hosts. However, longitudinal studies
      investigating the changes in metabolic characteristics, gut microbiota, and gut
      permeability of sows throughout pregnancy and lactation are lacking. The
      correlation between gut microbiota and metabolic status of sows is also poorly
      known. The present study was conducted to investigate the temporal variations in
      sow metabolic characteristics, gut microbiota, gut permeability, and gut
      inflammation at days 30 (G30) and 109 (G109) of gestation and days 3 (L3) and 14
      (L14) of lactation. Results showed that insulin sensitivity was decreased in L3.
      Circulating concentrations of pro-inflammatory cytokine IL-6 increased in G109
      and L3. 16S rRNA gene sequencing of the V3-V4 region showed that gut microbiota
      changed dramatically across different reproductive stages. The bacterial
      abundance and alpha diversity in L3 were the lowest. The phyla Proteobacteria and
      Fusobacteria exhibited the highest relative abundance in L3. Among the genera,
      Bacteroides, Escherichia_Shigella, and Fusobacterium were highest, but
      Oscillospira the lowest, in relative abundance in L3. The fecal levels of acetate
      and total short-chain fatty acids were increased in G109, but fecal butyrate
      concentrations were markedly decreased in L3. The plasma zonulin concentrations,
      a biomarker for gut permeability, were increased in G109 and L3. The plasma
      endotoxin concentrations were increased in L3. Furthermore, levels of fecal
      lipocalin-2 and pro-inflammatory cytokines IL-6 and TNF-alpha were increased in
      G109 and L3. In contrast, fecal levels of anti-inflammatory cytokine IL-10 were
      significantly decreased in G109 and L3. Additionally, the increased relative
      abundances of Fusobacterium in L3 were positively correlated with plasma zonulin
      and fecal endotoxin but negatively correlated with fecal IL-10. These findings
      indicate that the mother sow exhibits a metabolic syndrome and dramatical changes
      in gut microbiota during perinatal period, especially in early lactation.
      Besides, increased gut permeability and plasma endotoxin concentrations caused by
      negative microbial changes would possibly be the potential mechanisms under which
      sow's metabolic disorders and inflammatory status were exacerbated during early
      lactation.

PMID- 30197634
TI  - The Hurdle Approach-A Holistic Concept for Controlling Food Safety Risks
      Associated With Pathogenic Bacterial Contamination of Leafy Green Vegetables. A
      Review.
AB  - Consumers appreciate leafy green vegetables such as baby leaves for their
      convenience and wholesomeness and for adding a variety of tastes and colors to
      their plate. In Western cuisine, leafy green vegetables are usually eaten fresh
      and raw, with no step in the long chain from seed to consumption where
      potentially harmful microorganisms could be completely eliminated, e.g., through
      heating. A concerning trend in recent years is disease outbreaks caused by
      various leafy vegetable crops and one of the most important foodborne pathogens
      in this context is Shiga toxin-producing Escherichia coli (STEC). Other pathogens
      such as Salmonella, Shigella, Yersinia enterocolitica and Listeria monocytogenes
      should also be considered in disease risk analysis, as they have been implicated
      in outbreaks associated with leafy greens. These pathogens may enter the
      horticultural value network during primary production in field or greenhouse via
      irrigation, at harvest, during processing and distribution or in the home
      kitchen/restaurant. The hurdle approach involves combining several mitigating
      approaches, each of which is insufficient on its own, to control or even
      eliminate pathogens in food products. Since the food chain system for leafy green
      vegetables contains no absolute kill step for pathogens, use of hurdles at
      critical points could enable control of pathogens that pose a human health risk.
      Hurdles should be combined so as to decrease the risk due to pathogenic microbes
      and also to improve microbial stability, shelf-life, nutritional properties and
      sensory quality of leafy vegetables. The hurdle toolbox includes different
      options, such as physical, physiochemical and microbial hurdles. The goal for
      leafy green vegetables is multi-target preservation through intelligently applied
      hurdles. This review describes hurdles that could be used for leafy green
      vegetables and their biological basis, and identifies prospective hurdles that
      need attention in future research.

PMID- 30197636
TI  - Segmented Filamentous Bacteria - Metabolism Meets Immunity.
AB  - Segmented filamentous bacteria (SFB) are a group of host-adapted, commensal
      organisms that attach to the ileal epithelium of vertebrate and invertebrate
      hosts. A genetic relative of the genus Clostridium, these morphologically unique
      bacteria display a replication and differentiation lifecycle initiated by
      epithelial tissue binding and filamentation. SFB intimately bind to the surface
      of absorptive intestinal epithelium without inducing an inflammatory response.
      Rather, their presence impacts the generation of innate and differentiation of
      acquired immunity, which impact the clearance of extracellular bacterial or
      fungal pathogens in the gastrointestinal and respiratory tracts. SFB have
      recently garnered attention due to their role in promoting adaptive and innate
      immunity in mice and rats through the differentiation and maturation of Th17
      cells in the intestinal tract and production of immunoglobulin A (IgA). SFB are
      the first commensal bacteria identified that impact the maturation and
      development of Th17 cells in mice. Recently, microbiome studies have revealed the
      presence of Candidatus Arthromitus (occasionally designated as Candidatus
      Savagella), a proposed candidate species of SFB, in higher proportions in higher
      performing flocks as compared to matched lower-performing flocks, suggesting that
      SFB may serve to establish a healthy gut and protect commercial turkeys from
      pathogens resulting in morbidity and decreased performance. In this review we
      seek to describe the life cycle, host specificity, and genetic capabilities of
      SFB, such as bacterial metabolism, and how these factors influence the host
      immunity and microbiome. Although the role of SFB to induce antigen-specific Th17
      cells in poultry is unknown, they may play an important role in modulating the
      immune response in the intestinal tract to promote resistance against some
      infectious diseases and promote food-safety. This review demonstrates the
      importance of studying and further characterizing commensal, host-specific
      bacteria in food-producing animals and their importance to animal health.

PMID- 30197637
TI  - Role of Short Chain Fatty Acids in Controlling Tregs and Immunopathology During
      Mucosal Infection.
AB  - Interactions between mucosal tissues and commensal microbes control appropriate
      host immune responses and inflammation, but very little is known about these
      interactions. Here we show that the depletion of resident bacteria using
      antibiotics (Abx) causes oral and gut immunopathology during oropharyngeal
      candidiasis (OPC) infection. Antibiotic treatment causes reduction in the
      frequency of Foxp3+ regulatory cells (Tregs) and IL-17A producers, with a
      concomitant increase in oral tissue pathology. While C. albicans (CA) is usually
      controlled in the oral cavity, antibiotic treatment led to CA dependent oral and
      gut inflammation. A combination of short chain fatty acids (SCFA) controlled the
      pathology in Abx treated mice, correlating to an increase in the frequency of
      Foxp3+, IL-17A+, and Foxp3+IL-17A+ double positive (Treg17) cells in tongue and
      oral draining lymph nodes. However, SCFA treatment did not fully reverse the gut
      inflammation suggesting that resident microbiota have SCFA independent
      homeostatic mechanisms in gut mucosa. We also found that SCFA potently induce
      Foxp3 and IL-17A expression in CD4+ T cells, depending on the cytokine milieu in
      vitro. Depletion of Tregs alone in FDTR mice recapitulated oral inflammation in
      CA infected mice, showing that Abx mediated reduction of Tregs was involved in
      infection induced pathology. SCFA did not control inflammation in Treg depleted
      mice in CA infected FDTR mice, showing that Foxp3+ T cell induction was required
      for the protective effect mediated by SCFA. Taken together, our data reveal that
      SCFA derived from resident bacteria play a critical role in controlling
      immunopathology by regulating T cell cytokines during mucosal infections. This
      study has broader implications on protective effects of resident microbiota in
      regulating pathological infections.

PMID- 30197638
TI  - A Review of the Effect of Management Practices on Campylobacter Prevalence in
      Poultry Farms.
AB  - Poultry is frequently associated with campylobacteriosis in humans, with
      Campylobacter jejuni being the most usual Campylobacter associated with disease
      in humans. Far-reaching research on Campylobacter was undertaken over the past
      two decades. This has resulted in interventions being put in place on farms and
      in processing plants. Despite these interventions, coupled with increased media
      coverage to educate the consumer on Campylobacter prevalence and
      campylobacteriosis, human health incidents are still high. Recent research is now
      shifting toward further understanding of the microorganisms to challenge
      interventions in place and to look at further and more relevant interventions for
      the reduction in human incidents. Farm practices play a key role in the control
      of colonization within poultry houses and among flocks. Prevalence at the farm
      level can be up to 100% and time of colonization may vary widely between flocks.
      Considerable research has been performed to understand how farm management and
      animal health practices can affect colonization on farms. This review will focus
      on farm practices to date as a baseline for future interventions as the
      microorganism becomes better understood. Further research is required to
      understand the chicken microbiome and factors influencing vertical transmission.
      The persistence of Campylobacter in animal and environmental reservoirs within
      and around farms requires further investigation to tailor farm practices toward
      preventing such reservoirs. IMPLICATIONS  This review gives an overview of farm
      practices and their effect on Campylobacter prevalence in poultry. Various
      elements of farm practices have been captured in this review.

PMID- 30197639
TI  - Transcriptomic Characterization of a Chicken Embryo Model Infected With Duck
      Hepatitis A Virus Type 1.
AB  - Duck hepatitis A virus type 1 (DHAV-1) is one of the most common and lethal
      pathogens in young ducklings. Live-attenuated DHAV vaccine (CH60 strain)
      developed by passaging in chicken embryos provided effective immune protection
      for ducklings. However, the accurate mechanism for such adaption in chicken
      embryos is not fully revealed. Here, we utilize RNA-sequencing to perform global
      transcriptional analysis of DHAV-1-innoculated embryonated livers along with
      histopathological and ultrastructural analysis. This study revealed that
      infection with DHAV-1 strain CH60 is associated with enhanced type I and II
      interferon responses, activated innate immune responses, elevated levels of
      suppressor of cytokine signaling 1 and 3 (SOCS1 and SOCS3) accompanied with
      abnormalities in multiple metabolic pathways. Excessive inflammatory and innate
      immune responses induced by the CH60 strain are related to severe liver damage.
      Our study presents a comprehensive characterization of the transcriptome of
      chicken embryos infected with DHAV-CH60 and provides insight for in-depth
      exploration of viral adaption and virus-host interactions.

PMID- 30197640
TI  - Commentary: Uterine Microbiota: Residents, Tourists, or Invaders?

PMID- 30197641
TI  - Low Peripheral T Follicular Helper Cells in Perinatally HIV-Infected Children
      Correlate With Advancing HIV Disease.
AB  - Background: T follicular helper (Tfh) cells are crucial for B cell
      differentiation and antigen-specific antibody production. Dysregulation of Tfh
      mediated B cell help weakens B cell responses in HIV infection. Moreover, Tfh
      cells in the lymph node and peripheral blood comprise a significant portion of
      the latent HIV reservoir. There is limited data on the effects of perinatal HIV
      infection on Tfh cells in children. We examined peripheral Tfh (pTfh) cell
      frequencies and phenotype in HIV-infected children and their associations with
      disease progression, immune activation, and B cell differentiation. Methods: In a
      Kenyan cohort of 76 perinatally HIV-infected children, comprised of 43 treatment
      naive (ART-) and 33 on antiretroviral therapy (ART+), and 42 healthy controls
      (HIV-), we identified memory pTfh cells, T cell activation markers, and B cell
      differentiation states using multi-parameter flow cytometry. Soluble CD163 and
      intestinal fatty acid-binding protein plasma levels were quantified by ELISA.
      Results: ART- children had reduced levels of pTfh cells compared with HIV-
      children that increased with antiretroviral therapy. HIV+ children had higher
      programmed cell death protein 1 (PD-1) expression on pTfh cells, regardless of
      treatment status. Low memory pTfh cells with elevated PD-1 levels correlated with
      advancing HIV disease status, indicated by increasing HIV viral loads and T cell
      and monocyte activation, and decreasing %CD4 and CD4:CD8 ratios. Antiretroviral
      treatment, particularly when started at younger ages, restored pTfh cell
      frequency and eliminated correlations with disease progression, but failed to
      lower PD-1 levels on pTfh cells and their associations with CD4 T cell
      percentages and activation. Altered B cell subsets, with decreased naive and
      resting memory B cells and increased activated and tissue-like memory B cells in
      HIV+ children, correlated with low memory pTfh cell frequencies. Last, HIV+
      children had decreased proportions of CXCR5+ CD8 T cells that associated with low
      %CD4 and CD4:CD8 ratios. Conclusion: Low memory pTfh cell frequencies with high
      PD-1 expression in HIV+ children correlate with worsening disease status and an
      activated and differentiated B cell profile. This perturbed memory pTfh cell
      population may contribute to weak vaccine and HIV-specific antibody responses in
      HIV+ children. Restoring Tfh cell capacity may be important for novel pediatric
      HIV cure and vaccine strategies.

PMID- 30197642
TI  - A Novel Function for 15-Lipoxygenases in Cholesterol Homeostasis and CCL17
      Production in Human Macrophages.
AB  - Arachidonate 15-lipoxygenase (ALOX15) and arachidonate 15-lipoxygenase, type B
      (ALOX15B) catalyze the dioxygenation of polyunsaturated fatty acids and are
      upregulated in human alternatively activated macrophages (AAMs) induced by Th2
      cytokine interleukin-4 (IL-4) and/or interleukin-13. Known primarily for roles in
      bioactive lipid mediator synthesis, 15-lipoxygenases (15-LOXs) have been
      implicated in various macrophage functions including efferocytosis and
      ferroptosis. Using a combination of inhibitors and siRNAs to suppress 15-LOX
      isoforms, we studied the role of 15-LOXs in cellular cholesterol homeostasis and
      immune function in naive and AAMs. Silencing or inhibiting the 15-LOX isoforms
      impaired sterol regulatory element binding protein (SREBP)-2 signaling by
      inhibiting SREBP-2 processing into mature transcription factor and reduced SREBP
      2 binding to sterol regulatory elements and subsequent target gene expression.
      Silencing ALOX15B reduced cellular cholesterol and the cholesterol intermediates
      desmosterol, lanosterol, 24,25-dihydrolanosterol, and lathosterol as well as
      oxysterols in IL-4-stimulated macrophages. In addition, attenuating both 15-LOX
      isoforms did not generally affect IL-4 gene expression but rather uniquely
      impacted IL-4-induced CCL17 production in an SREBP-2-dependent manner resulting
      in reduced T cell migration to macrophage conditioned media. In conclusion, we
      identified a novel role for ALOX15B, and to a lesser extent ALOX15, in
      cholesterol homeostasis and CCL17 production in human macrophages.

PMID- 30197643
TI  - Control of Germinal Center Responses by T-Follicular Regulatory Cells.
AB  - Regulatory T-cells (Treg cells), expressing the transcription factor Foxp3, have
      an essential role in the control of immune homeostasis. In order to control
      diverse types of immune responses Treg cells must themselves show functional
      heterogeneity to control different types of immune responses. Recent advances
      have made it clear that Treg cells are able to mirror the homing capabilities of
      known T-helper subtypes such as Th1, Th2, Th17, and T-follicular helper cells
      (Tfh), allowing them to travel to the sites of inflammation and deliver
      suppression in situ. One of the more recent discoveries in this category is the
      description of T-follicular regulatory (Tfr) cells, a specialized subset of Treg
      cells that control Tfh and resulting antibody responses. In this review we will
      discuss recent advances in our understanding of Tfr biology and the role of both
      Tfr and activated extra-follicular Tregs (eTreg) in the control of humoral
      immunity.

PMID- 30197644
TI  - Graft Pre-conditioning by Peri-Operative Perfusion of Kidney Allografts With
      Rabbit Anti-human T-lymphocyte Globulin Results in Improved Kidney Graft Function
      in the Early Post-transplantation Period-a Prospective, Randomized Placebo
      Controlled Trial.
AB  - Introduction: Although prone to a higher degree of ischemia reperfusion injury
      (IRI), the use of extended criteria donor (ECD) organs has become reality in
      transplantation. We therefore postulated that peri-operative perfusion of renal
      transplants with anti-human T-lymphocyte globulin (ATLG) ameliorates IRI and
      results in improved graft function. Methods: We performed a randomized, single
      blinded, placebo-controlled trial involving 50 kidneys (KTx). Prior to
      implantation organs were perfused and incubated with ATLG (AP) (n = 24 kidney).
      Control organs (CP) were perfused with saline only (n = 26 kidney). Primary
      endpoint was defined as graft function reflected by serum creatinine at day 7
      post transplantation (post-tx). Results: AP-KTx recipients illustrated
      significantly better graft function at day 7 post-tx as reflected by lower
      creatinine levels, whereas no treatment effect was observed after 12 months
      surveillance. During the early hospitalization phase, 16 of the 26 CP-KTx
      patients required dialysis during the first 7 days post-tx, whereas only 10 of
      the 24 AP-KTx patients underwent dialysis. No treatment-specific differences were
      detected for various lymphocytes subsets in the peripheral blood of patients.
      Additionally, mRNA analysis of 0-h biopsies post incubation with ATLG revealed no
      changes of intragraft inflammatory expression patterns between AP and CP organs.
      Conclusion: We here present the first clinical study on peri-operative organ
      perfusion with ATLG illustrating improved graft function in the early period post
      kidney transplantation. Clinical Trial Registration: www.ClinicalTrials.gov,
      NCT03377283.

PMID- 30197645
TI  - Establishment and Characterization of a Functionally Competent Type 2
      Conventional Dendritic Cell Line.
AB  - Dendritic cells (DCs) are the most potent antigen presenting cells and possess an
      incomparable ability to activate and instruct T cells, which makes them one of
      the cornerstones in the regulation of the cross-talk between innate and adaptive
      immunity. Therefore, a deep understanding of DC biology lays the foundations to
      describe and to harness the mechanisms that regulate the development of the
      adaptive response, with clear implications in a vast array of fields such as the
      study of autoimmune diseases and the development of new vaccines. However, the
      great difficulty to obtain large quantities of viable non-activated DCs for
      experimentation have considerably hindered the progress of DC research. Several
      strategies have been proposed to overcome these limitations by promoting an
      increase of DC abundance in vivo, by inducing DC development from DC progenitors
      in vitro and by generating stable DC lines. In the past years, we have described
      a method to derive immortalized stable DC lines, named MutuDCs, from the spleens
      of Mushi1 mice, a transgenic mouse strain that express the simian virus 40 Large
      T-oncogene in the DCs. The comparison of these DC lines with the vast variety of
      DC subsets described in vivo has shown that all the MutuDC lines that we have
      generated so far have phenotypic and functional features of type 1 conventional
      DCs (cDC1s). With the purpose of deriving DC lines with characteristics of type 2
      conventional DCs (cDC2s), we bred a new Batf3-/- Mushi1 murine line in which the
      development of the cDC1 subset is severely defective. The new MutuDC line that we
      generated from Batf3-/- Mushi1 mice was phenotypically and functionally
      characterized in this work. Our results demonstrated that all the tested
      characteristics of this new cell line, including the expression of subset
      determining transcription factors, the profile of cytokine production and the
      ability to present antigens, are comparable with the features of splenic CD4-
      cDC2s. Therefore, we concluded that our new cell line, that we named CD4- MutuDC2
      line, represents a valuable model for the CD4- cDC2 subset.

PMID- 30197646
TI  - Hepatitis C Virus Envelope Glycoproteins: A Balancing Act of Order and Disorder.
AB  - Chronic hepatitis C virus infection often leads to liver cirrhosis and primary
      liver cancer. In 2015, an estimated 71 million people were living with chronic
      HCV. Although infection rates have decreased in many parts of the world over the
      last several decades, incidence of HCV infection doubled between 2010 and 2014 in
      the United States mainly due to increases in intravenous drug use. The approval
      of direct acting antiviral treatments is a necessary component in the elimination
      of HCV, but inherent barriers to treatment (e.g., cost, lack of access to
      healthcare, adherence to treatment, resistance, etc.) prevent dramatic
      improvements in infection rates. An effective HCV vaccine would significantly
      slow the spread of the disease. Difficulties in the development of an HCV culture
      model system and expression of properly folded- and natively modified-HCV
      envelope glycoproteins E1 and E2 have hindered vaccine development efforts. The
      recent structural and biophysical studies of these proteins have demonstrated
      that the binding sites for the cellular receptor CD-81 and neutralizing
      antibodies are highly flexible in nature, which complicate vaccine design.
      Furthermore, the interactions between E1 and E2 throughout HCV infection is
      poorly understood, and structural flexibility may play a role in shielding
      antigenic epitopes during infection. Here we discuss the structural complexities
      of HCV E1 and E2.

PMID- 30197648
TI  - Clonally Expanded Decidual Effector Regulatory T Cells Increase in Late Gestation
      of Normal Pregnancy, but Not in Preeclampsia, in Humans.
AB  - Background: Regulatory T (Treg) cells are necessary for the maintenance of
      allogenic pregnancy. However, the repertoire of effector Treg cells at the feto
      maternal interface in human pregnancy remains unknown. Our objective was to study
      T cell receptor (TCR) repertoires of Treg cells during pregnancy compared to
      normal and complicated pregnancies. Methods:Paired samples of peripheral blood
      and decidua in induced abortion and miscarriage cases were obtained from
      consenting patients. CD4+CD25+CD127low/-CD45RA- effector Treg cells were single
      cell sorted from mononuclear cells. cDNAs of complementarity determining region 3
      (CDR3) in TCRbeta were amplified from the single cells by RT-PCR and the
      sequences were analyzed. The TCRbeta repertoires were determined by amino acid
      and nucleotide sequences. Treg cells were classified into clonally expanded and
      non-expanded populations by CDR3 sequences. Results: We enrolled nine induced
      abortion cases in the 1st trimester, 12 cases delivered without complications in
      the 3rd trimester, 11 miscarriages with abnormal chromosomal karyotyped embryo,
      seven miscarriages with normal chromosomal karyotyped embryo, and seven cases of
      preeclampsia [median gestational week (interquartile range): 7 (7-9), 39 (38-40),
      9 (8-10), 8 (8-10), and 34 (32-37), respectively]. The frequency of clonally
      expanded populations of effector Treg cells increased in decidua of 3rd trimester
      cases compared to 1st trimester cases [4.5% (1.4-10.8%) vs. 20.9% (15.4-28.1%), p
      < 0.001]. Clonally expanded Treg cells were rarely seen in peripheral blood. The
      ratio of clonally expanded populations of decidual effector Treg cells in
      miscarriages with abnormal and normal embryos was not significantly different
      compared with that in 1st trimester normal pregnancy. Interestingly, clonally
      expanded populations of effector Treg cells decreased in preeclampsia compared
      with that in 3rd trimester normal pregnancy [9.3% (4.4-14.5%) vs. 20.9% (15.4
      28.1%), p = 0.003]. When repertoires in previous pregnancy and subsequent
      pregnancy were compared, some portions of the repertoire were shared. Conclusion:
      TCR repertoires of decidual effector Treg cells are skewed in the 3rd trimester
      of normal pregnancy. Failure of clonal expansion of populations of decidual
      effector Treg cells might be related to the development of preeclampsia.

PMID- 30197649
TI  - Alleles Causing Resistance to Isoxaben and Flupoxam Highlight the Significance of
      Transmembrane Domains for CESA Protein Function.
AB  - The cellulose synthase (CESA) proteins in Arabidopsis play an essential role in
      the production of cellulose in the cell walls. Herbicides such as isoxaben and
      flupoxam specifically target this production process and are prominent cellulose
      biosynthesis inhibitors (CBIs). Forward genetic screens in Arabidopsis revealed
      that mutations that can result in varying degrees of resistance to either
      isoxaben or flupoxam CBI can be attributed to single amino acid substitutions in
      primary wall CESAs. Missense mutations were almost exclusively present in the
      predicted transmembrane regions of CESA1, CESA3, and CESA6. Resistance to
      isoxaben was also conferred by modification to the catalytic residues of CESA3.
      This resulted in cellulose deficient phenotypes characterized by reduced
      crystallinity and dwarfism. However, mapping of mutations to the transmembrane
      regions also lead to growth phenotypes and altered cellulose crystallinity
      phenotypes. These results provide further genetic evidence supporting the
      involvement of CESA transmembrane regions in cellulose biosynthesis.

PMID- 30197647
TI  - The Unsolved Jigsaw Puzzle of the Immune Response in Chagas Disease.
AB  - Trypanosoma cruzi interacts with the different arms of the innate and adaptive
      host's immune response in a very complex and flowery manner. The history of host
      parasite co-evolution has provided this protozoan with means of resisting,
      escaping or subverting the mechanisms of immunity and establishing a chronic
      infection. Despite many decades of research on the subject, the infection remains
      incurable, and the factors that steer chronic Chagas disease from an asymptomatic
      state to clinical onset are still unclear. As the relationship between T. cruzi
      and the host immune system is intricate, so is the amount and diversity of
      scientific knowledge on the matter. Many of the mechanisms of immunity are fairly
      well understood, but unveiling the factors that lead each of these to success or
      failure, within the coordinated response as a whole, requires further research.
      The intention behind this Review is to compile the available information on the
      different aspects of the immune response, with an emphasis on those phenomena
      that have been studied and confirmed in the human host. For ease of
      comprehension, it has been subdivided in sections that cover the main humoral and
      cell-mediated components involved therein. However, we also intend to underline
      that these elements are not independent, but function intimately and concertedly.
      Here, we summarize years of investigation carried out to unravel the puzzling
      interplay between the host and the parasite.

PMID- 30197650
TI  - A Novel Approach to Assess Salt Stress Tolerance in Wheat Using Hyperspectral
      Imaging.
AB  - Salinity stress has significant adverse effects on crop productivity and yield.
      The primary goal of this study was to quantitatively rank salt tolerance in wheat
      using hyperspectral imaging. Four wheat lines were assayed in a hydroponic system
      with control and salt treatments (0 and 200 mM NaCl). Hyperspectral images were
      captured one day after salt application when there were no visual symptoms.
      Subsequent to necessary preprocessing tasks, two endmembers, each representing
      one of the treatment, were identified in each image using successive volume
      maximization. To simplify image analysis and interpretation, similarity of all
      pixels to the salt endmember was calculated by a technique proposed in this
      study, referred to as vector-wise similarity measurement. Using this approach
      allowed high-dimensional hyperspectral images to be reduced to one-dimensional
      gray-scale images while retaining all relevant information. Two methods were then
      utilized to analyze the gray-scale images: minimum difference of pair assignments
      and Bayesian method. The rankings of both methods were similar and consistent
      with the expected ranking obtained by conventional phenotyping experiments and
      historical evidence of salt tolerance. This research highlights the application
      of machine learning in hyperspectral image analysis for phenotyping of plants in
      a quantitative, interpretable, and non-invasive manner.

PMID- 30197653
TI  - Impact of Cultivar and Grafting on Nutrient and Water Uptake by Sweet Pepper
      (Capsicum annuum L.) Grown Hydroponically Under Mediterranean Climatic
      Conditions.
AB  - In closed-cycle hydroponic systems (CHS), nutrients and water should be delivered
      to the plants at identical ratios to those they are removed via plant uptake, to
      avoid their depletion or accumulation in the root zone. For a particular plant
      species and developmental stage, the nutrient to water uptake ratios, henceforth
      termed "uptake concentrations" (UC), remain relatively constant over time under
      similar climatic conditions. Thus, the nutrient to water uptake ratios can be
      used as nutrient concentrations in the nutrient solution (NS) supplied to CHS to
      compensate for nutrient and water uptake by plants. In the present study, mean UC
      of macro- and micronutrients were determined during five developmental stages in
      different pepper cultivars grown in a closed hydroponic system by measuring the
      water uptake and the nutrient removal from the recirculating NS. The experiment
      was conducted in a heated glasshouse located in Athens Mediterranean environment
      and the tested cultivars were 'Orangery,' 'Bellisa,' 'Sondela,' 'Sammy,' self
      grafted and 'Sammy' grafted onto the commercial rootstock 'RS10' (Capsicum
      annuum). 'Sondela' exhibited significantly higher NO3-, Mg2+, Ca2+ and B UC,
      while Bellisa exhibited higher K UC in comparison with all other cultivars. The
      UC of all nutrients were similar in the grafted and the non-grafted 'Sammy'
      plants, which indicates that this Capsicum annum rootstock does not modify the
      uptake of nutrients and water by the scion. The UC of macronutrients estimated in
      the present study (mmol L-1) ranged from 2.4 to 3.7 for Ca, 1.0 to 1.5 for Mg,
      6.2 to 9.0 for K, 11.7 to 13.7 for N, and 0.7 to 1.1 for P. The UC of N, K, Ca,
      and Mg were appreciably higher than the corresponding values found in Dutch
      tomato glasshouse, while that of P was similar in both locations during the
      vegetative stage and higher in the present study thereafter. The UC of Fe, Zn and
      B tended to decrease with time, while that of Mn increased initially and
      subsequently decreased slightly during the reproductive developmental stage.

PMID- 30197652
TI  - Benzyl Cyanide Leads to Auxin-Like Effects Through the Action of Nitrilases in
      Arabidopsis thaliana.
AB  - Plants within the Brassicales order generate glucosinolate hydrolysis products
      that can exert different biological effects on several organisms. Here, we
      evaluated the physiological effects of one of these compounds, benzyl cyanide
      (phenylacetonitrile), when exogenously applied on Arabidopsis thaliana. Treatment
      with benzyl cyanide led to a dose-dependent reduction of primary root length and
      total biomass. Further morphological changes like elongated hypocotyls, epinastic
      cotyledons, and increased formation of adventitious roots resembled a severe
      auxin-overproducer phenotype. The elevated auxin response was confirmed by
      histochemical staining and gene expression analysis of auxin-responsive genes.
      Nitriles are converted by specific enzymes, nitrilases (NIT1-3), to their
      corresponding carboxylic acids. The nitrilase mutants nit1 and nit2 tolerated
      benzyl cyanide treatments better than the wild type, with nit2 being less
      resistant than nit1. A NIT2RNAi line suppressing several nitrilases was resistant
      to all tested benzyl cyanide concentrations. When exposed to phenylacetic acid
      (PAA) - the corresponding carboxylic acid of benzyl cyanide - wild type and
      mutant seedlings were, however, equally susceptible and showed a more severe
      auxin phenotype than upon cyanide treatment. Here, we demonstrate that the auxin
      like effects triggered by benzyl cyanide on Arabidopsis are due to its nitrilase
      mediated conversion to the natural auxin PAA.

PMID- 30197651
TI  - De novo Transcriptome Characterization of Rhodomyrtus tomentosa Leaves and
      Identification of Genes Involved in alpha/beta-Pinene and beta-Caryophyllene
      Biosynthesis.
AB  - Plant-derived terpenes are effective in treating chronic dysentery, rheumatism,
      hepatitis, and hyperlipemia. Thus, understanding the molecular basis of terpene
      biosynthesis in some terpene-abundant Chinese medicinal plants is of great
      importance. Abundant in mono- and sesqui-terpenes, Rhodomyrtus tomentosa (Ait.)
      Hassk, an evergreen shrub belonging to the family Myrtaceae, is widely used as a
      traditional Chinese medicine. In this study, (+)-alpha-pinene and beta
      caryophyllene were detected to be the two major components in the leaves of R.
      tomentosa, in which (+)-alpha-pinene is higher in the young leaves than in the
      mature leaves, whereas the distribution of beta-caryophyllene is opposite. Genome
      wide transcriptome analysis of leaves identified 138 unigenes potentially
      involved in terpenoid biosynthesis. By integrating known biosynthetic pathways
      for terpenoids, 7 candidate genes encoding terpene synthase (RtTPS1-7) that
      potentially catalyze the last step in pinene and caryophyllene biosynthesis were
      further characterized. Sequence alignment analysis showed that RtTPS1, RtTPS3 and
      RtTPS4 do not contain typical N-terminal transit peptides (62-64aa), thus
      probably producing multiple isomers and enantiomers by terpenoid isomerization.
      Further enzyme activity in vitro confirmed that RtTPS1-4 mainly produce (+)-alpha
      pinene and (+)-beta-pinene, as well as small amounts of (-)-alpha-pinene and (-)
      beta-pinene with GPP, while RtTPS1 and RtTPS3 are also active with FPP, producing
      beta-caryophyllene, along with a smaller amount of alpha-humulene. Our results
      deepen the understanding of molecular mechanisms of terpenes biosynthesis in
      Myrtaceae.

PMID- 30197654
TI  - The Enhancement of Plant Disease Resistance Using CRISPR/Cas9 Technology.
AB  - Genome editing technologies have progressed rapidly and become one of the most
      important genetic tools in the implementation of pathogen resistance in plants.
      Recent years have witnessed the emergence of site directed modification methods
      using meganucleases, zinc finger nucleases (ZFNs), transcription activator-like
      effector nucleases (TALENs), and clustered regularly interspaced short palindrome
      repeats (CRISPR)/CRISPR-associated protein 9 (Cas9). Recently, CRISPR/Cas9 has
      largely overtaken the other genome editing technologies due to the fact that it
      is easier to design and implement, has a higher success rate, and is more
      versatile and less expensive. This review focuses on the recent advances in plant
      protection using CRISPR/Cas9 technology in model plants and crops in response to
      viral, fungal and bacterial diseases. As regards the achievement of viral disease
      resistance, the main strategies employed in model species such as Arabidopsis and
      Nicotiana benthamiana, which include the integration of CRISPR-encoding sequences
      that target and interfere with the viral genome and the induction of a CRISPR
      mediated targeted mutation in the host plant genome, will be discussed.
      Furthermore, as regards fungal and bacterial disease resistance, the strategies
      based on CRISPR/Cas9 targeted modification of susceptibility genes in crop
      species such as rice, tomato, wheat, and citrus will be reviewed. After spending
      years deciphering and reading genomes, researchers are now editing and rewriting
      them to develop crop plants resistant to specific pests and pathogens.

PMID- 30197655
TI  - High-Resolution Genetic Map and QTL Analysis of Growth-Related Traits of Hevea
      brasiliensis Cultivated Under Suboptimal Temperature and Humidity Conditions.
AB  - Rubber tree (Hevea brasiliensis) cultivation is the main source of natural rubber
      worldwide and has been extended to areas with suboptimal climates and lengthy
      drought periods; this transition affects growth and latex production. High
      density genetic maps with reliable markers support precise mapping of
      quantitative trait loci (QTL), which can help reveal the complex genome of the
      species, provide tools to enhance molecular breeding, and shorten the breeding
      cycle. In this study, QTL mapping of the stem diameter, tree height, and number
      of whorls was performed for a full-sibling population derived from a GT1 and
      RRIM701 cross. A total of 225 simple sequence repeats (SSRs) and 186 single
      nucleotide polymorphism (SNP) markers were used to construct a base map with 18
      linkage groups and to anchor 671 SNPs from genotyping by sequencing (GBS) to
      produce a very dense linkage map with small intervals between loci. The final map
      was composed of 1,079 markers, spanned 3,779.7 cM with an average marker density
      of 3.5 cM, and showed collinearity between markers from previous studies.
      Significant variation in phenotypic characteristics was found over a 59-month
      evaluation period with a total of 38 QTLs being identified through a composite
      interval mapping method. Linkage group 4 showed the greatest number of QTLs (7),
      with phenotypic explained values varying from 7.67 to 14.07%. Additionally, we
      estimated segregation patterns, dominance, and additive effects for each QTL. A
      total of 53 significant effects for stem diameter were observed, and these
      effects were mostly related to additivity in the GT1 clone. Associating accurate
      genome assemblies and genetic maps represents a promising strategy for
      identifying the genetic basis of phenotypic traits in rubber trees. Then, further
      research can benefit from the QTLs identified herein, providing a better
      understanding of the key determinant genes associated with growth of Hevea
      brasiliensis under limiting water conditions.

PMID- 30197657
TI  - Baseline IGFBP - 3 as the Key Element to Predict Growth Response to Growth
      Hormone and IGF - 1 Therapy in Subjects with Non - GH Deficient Short Stature and
      IGF - 1 Deficiency.
AB  - Background: Short stature in children represents a heterogeneous group with
      different etiologies. Primary Insulin like growth factor 1 (IGF - 1) deficiency
      in short stature can present with normal or elevated growth hormone (GH)
      production. Currently there is no model that can reliably predict response to
      recombinant (r)GH therapy and/or rIGF - 1 therapy in children with non - GH
      deficient short stature. Hypothesis: Baseline Insulin like growth factor binding
      protein 3 (IGFBP - 3) along with ? IGF - 1 in the first 3 months of GH therapy
      level can be a marker of growth response to the rGH and/or rIGF - 1 therapy in
      children with non - growth hormone deficiency short stature. Objectives: To study
      the relationship between baseline IGFBP - 3 and IGF - 1 levels and the response
      to rGH and rIGF - 1 therapy in children with short stature, normal GH secretion
      and low IGF - 1 SDS. Methods: 43 children, age 9.07 +/- 2.75 years with height 
      2.72 +/- 0.7 SD and baseline IGF - 1 of -2.76 +/- 0.58 SD, who passed the growth
      hormone releasing hormone (GHRH) stimulation test were included in a
      retrospective chart review. They were treated with rGH therapy with a mean dose
      of 0.46 +/- 0.1 mg/kg/week. Growth velocity (GV), IGF - 1 and IGFBP - 3 levels
      were done at 3 and 6 months of therapy. Subjects with poor response to rGH after
      6 months of therapy were switched to rIGF - 1 therapy at 0.24 mg/kg/day for the
      next 6 months. Subjects were divided according to their growth rate into
      responders to rGH (N = 23); non - responders to rGH, responders to rIGF - 1 (N =
      14) and non - responders to rGH and rIGF-1 (N = 6). Results: There was no
      correlation between GV and peak GH level at GHRH test. Growth velocity positively
      correlated with DeltaIGF - 1 SD among subjects treated with rGH therapy. Height
      SD positively correlated with IGFBP - 3 SD. Baseline IGFBP - 3 also inversely
      correlated with GH peak during GHRH test. Conclusions: In subjects with short
      stature and low IGF - 1 level, baseline IGFBP - 3 levels can predict the growth
      response to rGH and/or rIGF - 1 therapy.

PMID- 30197658
TI  - Factors Associated with Pre-Hypertension Among Tehranian Adults: A Novel
      Application of Structural Equation Models.
AB  - Background: Pre-hypertension is proposed as an independent risk factor for the
      incidence of cardiovascular diseases. Objectives: This study aimed to explore the
      main factors associated with pre-hypertension via testing a hypothesized model in
      Tehranian adults. Methods: The study was conducted within the framework of the
      Tehran Lipid and Glucose Study (TLGS) between 2009 - 2011 on 4640 adults without
      hypertension, aged >= 20 years. Results: The mean age of participants was 38.61
      +/- 12.14 years and 56.6% of them were female. More than one third of the studied
      participants had pre-hypertension (35.4%) with significantly higher prevalence in
      males compared to females (46.5% vs. 26.9%; chi2 = 190.7, P < 0.001). Age, waist
      circumference (WC), and serum triglyceride concentrations (TG) were directly
      associated with pre-hypertension in both men (beta = 0.16, beta = 0.25, and beta
      = 0.11, respectively) and women (beta = 0.16, beta = 0.21 and beta = 0.09,
      respectively). Physical activity, only in men (beta = 0.07), and marital status
      only, in women (beta = -0.06), were also directly associated with pre
      hypertension. Both healthy and poor dietary patterns showed indirect associations
      with pre-hypertension in both genders via WC and TG. Higher age and lower
      education in both genders, being married only in men, and unemployed status only
      in women, were positively associated with pre-hypertension via behavioral and
      cardio-metabolic factors. Conclusions: Level of TG and WC in both genders are
      direct modifiable associated factors of pre-hypertension. These findings could be
      considered in designing future health promotion programs aimed at preventing high
      blood pressure and its consequences among Tehranian adults.

PMID- 30197659
TI  - The Effects of Chemical Castration with Degarelix on Bone Turnover: Densitometric
      and Biomechanics Bone Properties of Male Rats.
AB  - Background: Gonadotropin releasing hormone (GnRH) antagonists may cause chemical
      castration in males by suppressing the pituitary-gonadal axis, hence reducing
      testosterone level. There are limited data on the effects of degarelix, a newer
      series of potent and long acting GnRH antagonist on bone. Objectives: The current
      study aimed at determining the effects of degarelix on bone turnover, bone
      densitometry, and bone mechanical strength in male rats. Methods: Eighteen male
      Sprague-Dawley rats were randomly divided into sham (SHAM), orchidectomized
      (ORX), and degarelix-induced (DGX) groups. Chemical castration was performed by
      subcutaneous degarelix injection (2 mg/kg) at the scapular region. The rats were
      scanned for baseline bone mineral area (BMA), bone mineral content (BMC), and
      bone mineral density (BMD) using dual-energy x-ray absorptiometry (DXA).
      Following six weeks of experimental period, BMA, BMC, and BMD were measured again
      with DXA and blood was collected for testosterone and bone biomarkers
      (osteocalcin and C-terminal of type I collagen crosslink (CTX-1)) measurements.
      The rats were euthanized and femora were dissected for bone biomechanical
      strength analysis. Results: Bilateral orchidectomy and degarelix administration
      significantly lowered serum testosterone level, decreased whole body BMC, femoral
      BMA, femoral BMC, and femoral BMD (P < 0.05) compared with the SHAM group.
      However, no significant changes were observed in bone biochemical markers and
      bone mechanical strength in all experimental groups. Conclusions: In conclusion,
      degarelix administration had comparable effects on bone as bilateral
      orchidectomy. Administration of degarelix provides an alternative method of
      inducing testosterone deficient-osteopenia in male rats without need for removing
      the testes.

PMID- 30197656
TI  - Curvilinear Association Between Language Disfluency and FMR1 CGG Repeat Size
      Across the Normal, Intermediate, and Premutation Range.
AB  - Historically, investigations of FMR1 have focused almost exclusively on the
      clinical effects of CGG expansion within the categories of the premutation (55
      200 CGG repeats) and fragile X syndrome (>200 CGG repeats). However, emerging
      evidence suggests that CGG-dependent phenotypes may occur across allele sizes
      traditionally considered within the "normal" range. This study adopted an
      individual-differences approach to determine the association between language
      production ability and CGG repeat length across the full range of normal,
      intermediate, and premutation alleles. Participants included 61 adult women with
      CGG repeats within the premutation (n = 37), intermediate (i.e., 41-54 repeats; n
      = 2), or normal (i.e., 6-40 repeats; n = 22) ranges. All participants were the
      biological mothers of a child with a developmental disorder, to control for the
      potential effects of parenting stress. Language samples were collected and the
      frequency of language disfluencies (i.e., interruptions in the flow of speech)
      served as an index of language production skills. Verbal inhibition skills,
      measured with the Hayling Sentence Completion Test, were also measured and
      examined as a correlate of language disfluency, consistent with theoretical work
      linking language disfluency with inhibitory deficits (i.e., the Inhibition
      Deficit Hypothesis). Blood samples were collected to determine FMR1 CGG repeat
      size. A general linear model tested CGG repeat size of the larger allele (allele
      2) as the primary predictor of language disfluency, covarying for education
      level, IQ, age, and CGG repeats on the other allele. A robust curvilinear
      association between CGG length and language disfluency was detected, where low
      normal (~ <25 repeats) and mid-premutation alleles (~90-110 repeats) were linked
      with higher rates of disfluency. Disfluency was not associated with inhibition
      deficits, which challenges prior theoretical work and suggests that a primary
      language deficit could account for elevated language disfluency in FMR1
      associated conditions. Findings suggest CGG-dependent variation in language
      production ability, which was evident across individuals with and without CGG
      expansions on FMR1.

PMID- 30197660
TI  - Spectrum of clinicohematological profile and its correlation with average
      parasite density in visceral leishmaniasis.
AB  - Background: Leishmaniasis is the prevalent in tropical and subtropical regions of
      the world. Demonstration of Leishman-Donovan (LD) bodies in the bone marrow
      aspirates (BMA) is vital to diagnosis of visceral leishmaniasis (VL). In the
      present study, we studied the clinicohematological parameters encountered in VL
      and correlated them with parasite load on BMA. Methods: Retrospective analysis
      over 3 years was done; clinical details, biochemical profile, complete hemogram
      with peripheral smear findings, and BMA smears were reviewed and average parasite
      density (APD) calculated in each case. Multivariate analysis and tests of
      significance were applied. Results: The study included 28 patients. Splenomegaly
      showed a positive trend with APD. rK39 antigen detection test was 100% positive
      in select cases. A strong negative correlation was observed between albumin to
      globulin ratio and grade of APD. BMA revealed hemophagocytosis (HPS) in 78.57%
      cases and it had a significant strong correlation with APD (P = 0.014). A
      significant correlation was also observed between APD and bone marrow plasma cell
      percentage (P = 0.01). LD bodies were noted in unusual locations such as within
      myelocytes (14.2%), plasma cells (7.1%), and megakaryocytes (10.7%). Conclusion:
      HPS and bone marrow plasmacytosis were two statistically significant findings,
      which showed positive correlation with parasite load. The presence of these two
      findings should prompt hematopathologists for more focused search of
      hemoparasites in BMA to arrive at a definitive diagnosis. This will avoid
      unnecessary workups and improve the prognosis. To the best of our knowledge, a
      statistical correlation between APD and clinicohematological parameters has never
      been previously studied.

PMID- 30197661
TI  - Cytological diagnosis of osteoblastoma of the talus: Case report with unusual
      presentation and diagnostic pitfalls.
AB  - Osteoblastoma is a rare bone tumor mostly affecting the young adults and commonly
      involving the spinal cord and long bones. Talus is the uncommon site of
      presentation, and if involved, then the neck is more commonly involved than the
      body of talus. The cytological diagnosis of osteoblastoma is limited, and to the
      best of our knowledge, its fine-needle aspiration (FNA) in the talus has still
      not been reported in the literature. The present case of osteoblastoma is,
      therefore, being reported due to the unusual presentation in elderly male in the
      body of talus and showing extensive involvement on X-ray. The case was initially
      diagnosed on FNA cytology excluding the possibility of giant-cell tumor and
      osteosarcoma. The case also highlights the importance of vigilant observation of
      subtle cytological features of this rare tumor which may be helpful in avoiding
      diagnostic pitfalls, especially at an uncommon site and with unusual
      presentation. An early precise diagnosis by cytology may be followed by
      appropriate treatment and thus avoiding any further complications.

PMID- 30197662
TI  - Lung tumor in a young African American patient with sickle trait: Pieces of a
      puzzle.

PMID- 30197664
TI  - A Data-Driven Approach to Appraisal and Selection at a Domain Data Repository.
AB  - Social scientists are producing an ever-expanding volume of data, leading to
      questions about appraisal and selection of content given finite resources to
      process data for reuse. We analyze users' search activity in an established
      social science data repository to better understand demand for data and more
      effectively guide collection development. By applying a data-driven approach, we
      aim to ensure curation resources are applied to make the most valuable data
      findable, understandable, accessible, and usable. We analyze data from a domain
      repository for the social sciences that includes over 500,000 annual searches in
      2014 and 2015 to better understand trends in user search behavior. Using a newly
      created search-to-study ratio technique, we identified gaps in the domain data
      repository's holdings and leveraged this analysis to inform our collection and
      curation practices and policies. The evaluative technique we propose in this
      paper will serve as a baseline for future studies looking at trends in user
      demand over time at the domain data repository being studied with broader
      implications for other data repositories.

PMID- 30197665
TI  - Pediatric residents' attitudes and practice patterns regarding transition to
      adult-oriented care.
AB  - Background: Most youth with chronic illness will survive into adulthood. The
      complexity of the medical history and care in these patients necessitates a well
      planned and coordinated transition over several years as they move from pediatric
      to adult-oriented health care. Methods: We assessed pediatric residents' practice
      patterns and attitudes regarding transition communication by administering a
      survey about transition to pediatric, combined internal medicine-pediatrics,
      pediatric neurology, and combined psychiatry-child psychiatry-pediatric
      residents. Results: Among 110 residents who were contacted, 66 completed the
      survey, for a response rate of 61%. Surveyed residents report discussing
      transition with their patients when their patients are age 18 or older, when
      guidelines suggest a discussion should begin around age 12. Most residents felt
      that transition should be initially addressed one year prior to transfer.
      Residents also reported barriers such as lack of experience with transition and
      lack of role modeling by supervisors as barriers to providing transitional care.
      Conclusions: The practice patterns and attitudes of pediatric residents in this
      study do not reflect the recommendations that have been published regarding
      transitional care services to prepare patients and families for transfer from
      pediatric to adult-oriented care. In particular, most residents report that they
      start transition discussions when a patient is near the age of 18, rather than
      the age of 12 as guidelines suggest and as families would prefer. Pediatric
      residents need further education regarding transition, with particular emphasis
      on the need for early and frequent discussions with patients and families
      regarding transition.

PMID- 30197663
TI  - The Prevalence of Autism Spectrum Disorders in Adult Psychiatric Inpatients: A
      Systematic Review.
AB  - Background: Whilst the prevalence of autism spectrum disorders in adults within
      the community setting is well-established, less is known about the prevalence
      among adults based within a psychiatric inpatient setting. Objective: To conduct
      a systematic literature review pertaining to the prevalence of autism spectrum
      disorders among the adult psychiatric inpatient population. Method: Eligibility
      criteria included: (a) investigation of the prevalence of autism spectrum
      disorders (b) adult psychiatric inpatient study population (c) published in
      English language. Electronic databases accessed included PubMed, Medline, CINAHL,
      PsycINFO and EMBASE. Additionally, the ancestry method was utilised for the
      references of eligible papers, as well as grey literature searches and
      consultation with experts in the field. Results: From the search, 4 studies were
      identified which satisfied the inclusion criteria, conducted in a variety of
      inpatient psychiatric settings, including secure forensic and intellectual
      disability units and a state psychiatric hospital. There were significant
      differences in methodological approaches, including the screening tests,
      diagnostic instruments and diagnostic criteria utilised. Autism spectrum disorder
      prevalence estimates varied considerably, from 2.4-9.9%. Conclusion: From the
      limited research data currently available, it appears that the prevalence of
      autism spectrum disorders is increased in inpatient psychiatric settings relative
      to the general population. There is a need for further high quality research in
      this patient group, to add to this limited evidence base, as well as in
      developing effective strategies to identify patients with a high likelihood of
      autism spectrum disorders within this setting.

PMID- 30197666
TI  - Effect of sheath material and reaction overpressure on Ag extrusions into the
      TiO2 insulation coating of Bi-2212 round wire.
AB  - In order to develop a high current density in coils, Bi-2212 wires must be
      electrically discrete in tight winding packs. It is vital to use an insulating
      layer that is thin, fulfils the dielectric requirements, and can survive the heat
      treatment whose maximum temperature reaches 890  degrees C. A thin (20-30 um)
      ceramic coating could be better as the insulating layer compared to alumino
      silicate braided fiber insulation, which is about 100 MUm thick and reacts with
      the Ag sheath during heat treatment, degrading the critical current density (Jc).
      At present, TiO2 seems to be the most viable ceramic material for such a thin
      insulation because it is chemically compatible with Ag and Bi-2212 and its
      sintering temperature is lower than the maximum temperature used for the Bi-2212
      heat treatment. However, recent tests of a large Bi-2212 coil insulated only with
      TiO2 showed severe electrical shorting between the wires after over pressure heat
      treatment (OPHT). The origin of the shorting was frequent silver extrusions that
      penetrated the porous TiO2 layer and electrically connected adjacent Bi-2212
      wires. To understand the mechanism of this unexpected behaviour, we investigated
      the effect of sheath material and hydrostatic pressure on the formation of Ag
      extrusions. We found that Ag extrusions occur only when TiO2-insulated Ag-0.2%Mg
      sheathed wire (Ag(Mg) wire) undergoes OPHT at 50 bar. No Ag extrusions were
      observed when the TiO2-insulated Ag(Mg) wire was processed at 1 bar. The TiO2
      insulated wires sheathed with pure Ag that underwent 50 bar OPHT were also free
      from Ag extrusions. A key finding is that the Ag extrusions emanating from the
      Ag(Mg) sheath actually contain no MgO, suggesting that local depletion of MgO
      facilitates local, heterogeneous deformation of the sheath under hydrostatic
      overpressure. Our study also suggests that predensifying the Ag(Mg) wire before
      insulating it with TiO2 and doing the final OPHT can potentially prevent Ag
      extrusion.

PMID- 30197667
TI  - Sorbus commixta water extract induces apoptotic cell death via a ROS-dependent
      pathway.
AB  - The stembark of Sorbus commixta Hedl. has been used for treating asthma,
      bronchitis, gastritis and edema. However, the anticancer and proapoptotic effects
      of the water extract of the stembark of S. commixta (SCE) remain unknown. In the
      present study, it was shown that SCE inhibited the cell viability of the
      hepatocellular carcinoma cell lines Hep3B and HepG2, and of the colon carcinoma
      cell line HCT116. DNA content analysis indicated that SCE increased the sub-G1
      population of HCT116 cells. In addition, degradation of nuclear DNA and levels of
      proapoptotic cascade components, including caspase-9, caspase-3 and poly ADP
      ribose polymerase, were augmented by SCE treatment. Mitochondrial membrane
      potential and the ratio of B-cell lymphoma-2 (Bcl-2)/Bcl-2-associated X protein
      (Bax) were also reduced. Furthermore, SCE increased the expression of
      proapoptotic proteins, including p21, p27 and p53. Mouse double minute 2
      homology, a negative regulator of p53, was cleaved by SCE treatment.
      Intracellular reactive oxygen species (ROS) production was also increased by SCE
      treatment. However, the SCE-induced cytotoxic effects and the increased
      expression of proapoptotic proteins, including p53 and p21, and reduced Bcl-2/Bax
      ratio, could be attenuated by N-acetyl cysteine, an ROS inhibitor. Taken
      together, these results indicate that SCE is a potent proapoptotic herbal
      medicine, which exerts its effects via the ROS-mediated mitochondrial pathway.

PMID- 30197668
TI  - Enhanced plasma miR-26a-5p promotes the progression of bladder cancer via
      targeting PTEN.
AB  - The current study aimed to evaluate the expression and specific role of miR-26a
      5p in the progression of bladder cancer (BC). Reverse transcription-quantitative
      polymerase chain reaction analysis was performed to evaluate the level of miR-26a
      5p in BC cancer and healthy controls. The present data showed that plasma miR-26a
      5p was significantly increased in BC patients. Furthermore, BC tissues exhibited
      greater levels of miR-26a-5p compared with adjacent non-neoplastic tissues-26a
      5p. Compared with BC patients at Ta-T1 stage, the level of miR-26a-5p was
      significantly elevated in BC patients >=T2. BC patients at G3 stage demonstrated
      a higher plasma miR-26a-5p level compared with those at G1/2 stage. Receiver
      operating characteristic (ROC) analysis indicated that miR-26a-5p could
      differentiate BC patients from controls. Additionally, Kaplan-Meier analysis
      demonstrated that plasma miR-26a-5p negatively correlated with survival of BC
      patients. Dual luciferase reporter assay indicated that miR-26a-5p significantly
      suppressed the relative luciferase activity of pmirGLO-PTEN-3'UTR compared with
      the control. In conclusion, the current study indicated novel data that the
      levels of plasma miR-26a-5p was significantly increased in BC patients.
      Furthermore, the present study suggested that determination of plasma miR-26a-5p
      level could help to distinguish BC patients from healthy controls via targeting
      PTEN.

PMID- 30197669
TI  - Human chorionic gonadotropin promotes cell proliferation through the activation
      of c-Met in gastric cancer cells.
AB  - Hormones and their receptors affect the development process of gastric cancer.
      Previous studies have revealed that human chorionic gonadotropin (hCG) is
      expressed in gastric cancer tissue. However, the mechanism by which hCG exerts
      its effects on gastric cancer cells had not been reported. In the present study,
      the expression of hCG and its receptor was detected in gastric cancer tissues and
      para-carcinoma tissues of 62 patients with gastric carcinoma. Following the
      treatment of gastric cancer cells SGC-7901 with hCG, a cell counting kit-8 assay,
      flow cytometry, a colony formation assay and a xenograft tumor model in nude mice
      were used to detect the effect of hCG on cell proliferation; and the expression
      of c-Met was determined by western blot analysis. The expression of hCG and its
      receptor were significantly higher in gastric cancer tissues compared with that
      of the matched para-carcinoma tissue (P<0.01). Proliferation of SGC-7901 cells
      treated with hCG was significant higher and the number of cells at the G2/M phase
      of the cell cycle increased compared with the control cells. Hepatocyte growth
      factor transmembrane protein receptor expression was increased in hCG-treated
      cells compared with the control cells, which relies on the protein kinase A
      signaling pathway. The present study revealed the potential function of hCG in
      the development of gastric cancer, suggesting that hCG may be a molecular marker
      and potential drug target in gastric cancer.

PMID- 30197670
TI  - Jinfukang induces cellular apoptosis through activation of Fas and DR4 in A549
      cells.
AB  - The traditional Chinese medicine Jinfukang (JFK) has been shown as a valuable
      drug to treat non-small cell lung cancer (NSCLC). Previously, it was reported
      that JFK-induced epigenetic alteration is involved in anti-lung cancer activity.
      In the present study, the effect of JFK on lung cancer cell lines was examined
      with the aim to further understand the underlying mechanisms of JFK-induced anti
      lung cancer activity by transcriptome profiling analysis. JFK was observed to
      decrease lung cancer cell viability and simultaneously induce cellular morphology
      alteration. Additionally, this causes cell cycle arrest and apoptosis in A549
      cells. The present RNA-seq analysis identified 5,281 genes with differential
      expression (P<0.05). Gene ontology analysis indicated that genes involved in the
      cell cycle pathway are downregulated, including cyclin-dependent kinase 2, cyclin
      dependent kinase 4, cyclin B1 and cyclin A2, and apoptosis-associated genes are
      upregulated, including Fas, death receptor 4 (DR4), tumor protein P53 binding
      protein 2 and BCL2 interacting protein 3 like. Particularly, the present results
      indicate knockdown of Fas and DR4 attenuates JFK-induced apoptosis in A549 cells.
      Overall, the present study suggests JFK induces cellular apoptosis through
      activation of Fas and DR4 in A549 cells and provides an insight for understanding
      the antitumor mechanisms of this Chinese traditional medicine.

PMID- 30197671
TI  - Effects of zerumbone on proliferation and apoptosis of esophageal cancer cells
      and on P53 and Bcl-2 expression levels.
AB  - The effects of zerumbone on the proliferation and apoptosis of esophagus cancer
      cells and on the P53 and Bcl-2 expression levels were studied. The esophagus
      cancer EC-109 cells were cultured and inoculated. The effect of zerumbone on
      proliferation of EC-109 cells was detected via the Cell Counting Kit-8 (CCK-8)
      method. Cell apoptosis was detected via TdT-mediated dUTP nick end-labeling
      (TUNEL) staining. Moreover, the mRNA expression levels of P53 and Bcl-2 were
      detected via reverse transcription-polymerase chain reaction (RT-PCR), and the
      protein expression levels of P53 and Bcl-2 were evaluated via western blotting.
      CCK-8 detection results showed that compared with control group, zerumbone in
      different concentrations could inhibit the activity of EC-109, and the
      proliferation inhibition rate was significantly increased in a concentration
      dependent manner with the increase of concentration. TUNEL staining showed that
      cell apoptosis gradually occurred in administration group, and the number of
      apoptotic cells was increased in a concentration-dependent manner with the
      increase of concentration. RT-PCR detection results showed that the mRNA
      expression level of P53 in administration group was significantly increased
      compared with that in control group, but that of Bcl-2 was significantly
      decreased. Western blotting showed that the protein expression level of Bcl-2 in
      administration group in different concentrations was significantly increased with
      the increase of zerumbone concentration, but that of Bcl-2 was significantly
      decreased in a concentration-dependent manner. Zerumbone can inhibit the
      proliferation and induce apoptosis of esophageal cancer EC-109 cells, and its
      induction of apoptosis may be realized through upregulating the mRNA expression
      of P53 and downregulating the mRNA expression of Bcl-2, and upregulating the
      protein expression of P53 and downregulating the protein expression of Bcl-2.

PMID- 30197672
TI  - Primary small cell neuroendocrine carcinoma of the Bartholin's gland: A case
      report.
AB  - Primary carcinoma of the Bartholin's gland (BG) is a rare malignancy. There are
      extremely rare cases of small cell neuroendocrine carcinoma (SCNC) of the BG
      reported in the English literature. A postmenopausal female presented with a 1
      month history of increasing pain and swelling on the left vulva consistent with
      spontaneously bleeding. Pathology identified SCNC that arose in BG. The patient
      was treated with a radical wide local excision and bilateral inguinal lymph node
      dissection followed by six courses of chemotherapy. One month after primary
      treatment, without any pelvic recurrence or abnormal tumor markers indications,
      distant metastasis of the liver was diagnosed and VI hepatic lobectomy was
      performed. The patient maintained regular adjuvant chemotherapy every month under
      outpatient surveillance and has no local recurrence or distant metastasis.

PMID- 30197673
TI  - Intensity-modulated radiotherapy for synchronous cancer of the anal canal and
      cervix.
AB  - Due to recent advancements in diagnostic techniques, the incidence of multiple
      primary cancer has increased; however, synchronous cancer of the anal canal and
      cervix (SCACC) is rare, and no previous studies have investigated the treatment
      of this disease. The present study reports a case in which intensity-modulated
      radiotherapy (IMRT) was used to treat a 64-year-old female with SCACC, inguinal
      lymphadenopathy and anal pain. The patient was diagnosed with cT3N3M0 stage IIIb
      anal canal squamous cell carcinoma and cT1b1N0M0 stage Ib1 cervical squamous cell
      carcinoma, based on biopsy and imaging study data. According to the definitive
      treatment for advanced-stage anal canal cancer, outpatient treatment with
      chemoradiotherapy (CRT) using S-1 for SCACC was recommended, as the patient did
      not want to undergo resection of the anus. Considering the lymph node regions
      involved in SCACC and the necessary doses, the treatment plan was as follows:
      Whole pelvis and inguinal lymph node region radiation (36 Gy/20 fractions); a
      first booster radiation dose (9 Gy/5 fractions) for the whole pelvis; and a
      second booster radiation dose (14.4 Gy/8 fractions) for the primary lesions. The
      patient was prescribed S-1 at a dose of 60 mg/m2/day twice daily on days 1-14 and
      29-42. The patient experienced grade 2 diarrhea and anal mucositis, but CRT was
      completed without discontinuation and hospitalization. The patient exhibited a
      complete response and remained disease-free without any treatment-associated
      complications at the 6-month follow-up. In conclusion, SCACC was successfully
      treated with IMRT in the present case. It is important to determine the treatment
      strategy for synchronous cancer types, taking into consideration the tumor stage,
      tumor location and patient situation.

PMID- 30197674
TI  - beta-Bourbonene attenuates proliferation and induces apoptosis of prostate cancer
      cells.
AB  - Sesquiterpenes have antitumor, anti-inflammation, and anti-fungal effects. beta
      bourbonene is a kind of sesquiterpene, but its pharmacological effect has not
      been studied. The present study was conducted in order to investigate the
      potential anticancer effects of beta-bourbonene on human prostate cancer PC-3M
      cells. PC-3M cells were incubated with 0, 25, 50, 100 ug/ml of beta-bourbonene.
      Cell Counting Kit-8 (CCK-8) detection showed that compared with the control
      group, beta-bourbonene inhibited the growth of PC-3M cells in a dose-dependent
      manner. G0/G1 phase arrest was observed by beta-bourbonene by using flow
      cytometry. TUNEL staining and Annexin V/PI dual-staining method revealed that
      apoptosis was found in cells with beta-bourbonene treatment, and the quantity of
      apoptotic cells was increased with the elevation in concentration. The mRNA and
      protein expression levels of Fas and FasL in the drug-treatment group were
      significantly elevated. Furthermore, the western blot assay also indicated that
      with an increase in the concentration of beta-bourbonene, the protein expression
      of Bax in the drug-treatment group was significantly elevated, while a decrease
      was identified in the protein expression of Bcl-2. Taken together, beta
      bourbonene can inhibit the proliferation and simultaneously, induce apoptosis and
      G0/G1 arrest of prostate cancer PC-3M cells, which may be realized by
      upregulation of mRNA expression of Fas and FasL, increase of Bax protein
      expression and decrease of Bcl-2 protein expression.

PMID- 30197675
TI  - Selective enrichment of CD133+/SOX2+ glioblastoma stem cells via adherent
      culture.
AB  - Most of the brain tumors are malignant with an extremely poor survival rate.
      Recent progress in identifying cancer stem cells (CSCs) within the brain tumors
      is starting to revolutionize our understanding in the imitation and progression
      of tumors as well as relapse and the development of therapeutic strategies.
      Suspension spheroid body culture paradigm is a routine method in enriching CSCs.
      While, it was reported recently that CSCs within the brain tumor may also be
      enriched through adherent monolayer culture with optimized properties. In the
      present study, 18 surgically resected brain tumors were used for analyzing the
      feasibility of adherent enrichment of CSCs. The results indicated that 50% of
      glioblastomas were able to generate adherent CSCs, which were uniformly positive
      for Sox2, CD133, GFAP and Nestin. However, adherent culture paradigm failed to
      yield CSCs in secondary brain tumors, including neurocytomas, ependymomas, germ
      cell tumors or low-grade astrocytomas, which is most likely due to a lack of
      CD133+/Sox2+ cells within the original biopsies. Therefore, it was concluded that
      the adherent culture paradigm may serve as a reliable method in enriching brain
      CSCs, but this method is more suitable for enriching CD133+/Sox2+ CSCs in
      glioblastomas.

PMID- 30197676
TI  - Rab-like protein 1 A is upregulated by cisplatin treatment and partially inhibits
      chemoresistance by regulating p53 activity.
AB  - Rab-like protein 1 A (RBEL1A), which is a predominant isoform of RBEL1, has been
      identified to serve an important function in breast tumorigenesis and may be
      upregulated in breast tumor cells. RBEL1A may block the transcriptional activity
      of p53, which is important in the induction of cisplatin sensitivity. Previous
      studies supported the association between the induction of chemoresistance and
      the inhibition of p53 by RBEL1A. However, the response of RBEL1A to
      chemotreatment and its interaction with p53 remains to be investigated. The
      present study revealed that the cisplatin treatment induced the expression of
      RBEL1A in MCF-7 cells. Consistent with previous studies, the present study
      demonstrated that cisplatin treatment and RBEL1A overexpression blocked the
      oligomerization of p53 in MCF-7 cells and led to a decrease of the
      transcriptional activity of p53 and its downstream target gene p21. Additionally,
      upregulation of RBEL1A decreased the protein level of p53 by promoting the
      ubiquitination of p53. A cytotoxicity assay demonstrated that upregulation of
      RBEL1A partially contributed to chemosensitivity via inhibiting p53 in MCF-7
      cells. A pG13L (p53-responsive reporter plasmid) luciferase reporter and co
      immunoprecipitation assay revealed that upregulation of RBEL1A led to an
      inhibition of the transcriptional activity of p53 or its target gene p21.
      Analysis of cellular proliferation, cell cycle and invasion also confirmed the
      regulatory activity of RBEL1A on the malignancy of breast cancer cells. Taken
      together, these results suggest that the induction of RBEL1A following cisplatin
      treatment may partially inhibit chemosensitivity in a p53-dependent manner.

PMID- 30197677
TI  - MAPK/AP-1 pathway regulates benzidine-induced cell proliferation through the
      control of cell cycle in human normal bladder epithelial cells.
AB  - Bladder cancer is the most common malignancy of the urinary tract. Long-term
      exposure to benzidine is one of the major causes of bladder cancer. However, the
      mechanism of benzidine-induced bladder cancer is not yet sufficiently
      characterized. Dysregulated cell proliferation serves a critical role in cancer
      initiation and development; whether benzidine promotes cell proliferation, and
      the role of MAPKs in this process, have not previously been investigated. The
      present study aimed to investigate the benzidine-induced modulation of
      intracellular mitogen-activated protein kinases (MAPKs) and activator protein-1
      (AP-1) signaling cascades on cell proliferation in SV-40 immortalized human
      uroepithelial cells (SV-HUC-1). It was identified that benzidine exposure
      enhanced the proliferation of SV-HUC-1 cells, promoted the transition of cells
      from G1 to S phase and altered the expression level of cell cycle-associated
      genes at the mRNA and protein levels. Furthermore, exposure of the SV-HUC-1 cells
      to benzidine was associated with the activation of MAPKs, including extracellular
      regulated protein kinases 1 and 2, p38 and Jun N-terminal kinase. The downstream
      target of MAPKs, AP-1 monomers, was also activated. Benzidine-induced
      proliferation was reversed by MAPK-specific inhibitors. Thus, the present study
      demonstrated that benzidine enhances the proliferation of bladder cells via
      activating the MAPK/AP-1 pathway, which may provide novel insights into the
      molecular mechanisms of benzidine-initiated bladder tumorigenesis, as well as
      cancer prevention.

PMID- 30197679
TI  - Synergistic antitumor effect of suberoylanilide hydroxamic acid and cisplatin in
      osteosarcoma cells.
AB  - Cisplatin, as a first-line chemotherapy drug, has been widely applied for therapy
      of osteosarcoma. However, its application is limited by drug resistance and
      serious side effects, including nephrotoxicity and ototoxicity. Suberoylanilide
      hydroxamic acid (SAHA) is a newly developed histone deacetylase (HDAC) inhibitor,
      which is the first Food and Drug Administration-approved HDAC inhibitor for the
      treatment of cutaneous manifestations of T-cell lymphoma. However, SAHA as a
      monotherapy was revealed to be limited, particularly in solid tumors. In the
      present study, 143B osteosarcoma cells were treated with multiple concentrations
      of SAHA or cisplatin, either alone or combined. The morphological characteristics
      of the treated cells were observed using an inverted microscope. The cytotoxicity
      effects of the combination of SAHA and cisplatin on 143B cells were analyzed by
      MTT assay, colony formation assay, wound healing cell migration assay, cell
      apoptosis assay and cell cycle analysis. Western blot analysis was performed to
      detect the protein expression levels of B cell lymphoma-2 (Bcl-2)-associated X
      protein (Bax), Bcl-2, cleaved-caspase-3, cleaved-caspase-8 and cleaved-poly (ADP
      ribose) polymerase (PARP). The experimental data indicated that the inhibition of
      cell proliferation in the combination group was significantly increased compared
      with that in single drug groups. Expression levels of pro-apoptotic protein were
      upregulated, whereas anti-apoptotic Bcl-2 was downregulated significantly in 143B
      cells following SAHA/cisplatin treatment. Taken together, the results revealed
      that the combination of SAHA and cisplatin inhibited the proliferation of 143B
      cells and induced their apoptosis synergistically, and this effectiveness may be
      mediated by caspase activation.

PMID- 30197678
TI  - Total ginsenosides of Chinese ginseng induces cell cycle arrest and apoptosis in
      colorectal carcinoma HT-29 cells.
AB  - Colorectal carcinoma (CRC) is the most frequent malignant disease of the
      gastrointestinal tract and it has a poor prognosis. The current treatment options
      for CRC are far from optimal; they have limited efficacy and toxic effects.
      Chinese ginseng (the dried root of Panax ginseng) is a medicinal herb, of which
      ginsenosides are the most effective anticancer component. The aim of the present
      study was to evaluate the anti-CRC effect of total ginsenosides of Chinese
      ginseng (TGCG), by analyzing the cellular and molecular pathways. This was done
      via MTT assay, morphological observation (DAPI staining), flow cytometry for cell
      cycle and apoptosis analyses, reverse transcription-quantitative polymerase chain
      reaction and western blot analysis. The results revealed that TGCG inhibited cell
      proliferation and induced cell cycle arrest and cell apoptosis in HT-29 cells in
      a dose-dependent manner. The mRNA expression of CDK2, CDK4, CDK6, BAX, CDKN2B,
      CASP8, CASP3, TP53, TOP1, MYC, MDM2, and CCND1 and the protein expression of
      cyclin-dependent kinase (Cdk) 2, Cdk4, Cyclin D1, Bax, p21WAF1, p27Kip1, c-Myc,
      p15INK4b, and p53 were revealed to be modulated by TGCG in HT-29 cells, and are
      all factors associated with DNA damage, cell proliferation, cell cycle and
      apoptosis. In conclusion, TGCG induced cell cycle arrest at the G0/G1 and G2/M
      phases and induced apoptosis in HT-29 cells through the c-Myc- and p53-mediated
      signaling pathways, possibly in response to DNA damage. Therefore, TGCG may be
      regarded a promising candidate for development as an anticancer agent for the
      treatment of CRC.

PMID- 30197680
TI  - Circulating long non-coding RNAs HULC and ZNFX1-AS1 are potential biomarkers in
      patients with gastric cancer.
AB  - Long non-coding RNAs (lncRNAs) have been demonstrated to be involved in different
      types of cancer, including gastric cancer. Although altered lncRNAs profiles have
      been observed in or around gastric cancer tissues, the diagnostic value of
      circulating lncRNAs in gastric cancer remains unclear. In the present study, a
      number of highly expressed lncRNAs, including uc001lsz, GACAT2, ABHD11-AS1,
      GACAT3, SUMP1P3, CHET1, TUG1, SNHG12, GAS5, PVT1, LINC00152, HOTAIR, CCAT1, H19,
      HULC and ZNFX1-AS1, were investigated as potential minimally invasive biomarkers
      for this tumor. Preliminary screening experiments revealed that ZNFX1-AS1 and
      HULC were differentially expressed in the plasma of gastric cancer patients and
      healthy control subjects. The study further examined the relative expression of
      ZNFX1-AS1 and HULC in the plasma of 50 matching preoperative and postoperative
      patients, 50 gastrointestinal stromal tumor (GIST) patients, 50 gastritis/peptic
      ulcer patients and 50 healthy control subjects through reverse transcription
      quantitative polymerase chain reaction. The correlation of lncRNA relative
      expression with the general characteristics and clinicopathological factors was
      analyzed. It was observed that the levels of ZNFX1-AS1 and HULC in the plasma of
      preoperative patients were markedly higher compared with those in the plasma of
      GIST patients, gastritis/peptic ulcer patients and healthy control subjects,
      while no significant difference was detected among these three groups. Receiver
      operating characteristic curve analysis was also conducted to distinguish gastric
      cancer patients from healthy control subjects. The area under the curve was 0.85
      and 0.65 for ZNFX1-AS1 and HULC, respectively. In conclusion, the results
      indicated that the lncRNAs ZNFX1-AS1 and HULC are promising in the clinical
      diagnosis of gastric cancer.

PMID- 30197681
TI  - miR-126/VCAM-1 regulation by naringin suppresses cell growth of human non-small
      cell lung cancer.
AB  - Certain studies have indicated that naringin possesses various pharmacological
      activities including anti-aging, anti-oxidation, anticancer, cardiovascular and
      cerebrovascular disease prevention, in addition to anti-hepatic effects. The
      present study explores the anticancer effect of naringin on human small cell lung
      cancer H69AR cells. Cell growth and apoptosis rates of H69AR cells were measured
      by MTT or flow cytometry, which demonstrated naringin suppressed cell growth and
      induced apoptosis of H69AR cells. MicroRNA (miR)-126 expression and levels of
      phosphorylated protein kinase B (AKT), mechanistic target of rapamycin (mTOR),
      nuclear factor (NF)-kappaB and vascular cell adhesion molecule 1 (VCAM-1)
      proteins were detected by quantitative polymerase chain reaction and western
      blotting. It was identified that naringin increased miR-126 expression and
      suppressed the phosphorylation of AKT, mTOR, NF-kappaB and VCAM-1 proteins in
      H69AR cells. Suppression of miR-126 expression reduced the anticancer effects of
      naringin on H69AR cells, reversed the naringin-induced reduction of
      phosphoinositide 3-kinase/AKT/mTOR, and suppressed VCAM-1 protein levels.
      However, close of miR-126 expression did not affect the levels of NF-kappaB
      protein in H69AR cells. In summary, naringin exhibits its anti-cancer effect by
      suppressing cell growth of small cell lung cancer cells through miR-126/VCAM-1
      signaling pathway.

PMID- 30197682
TI  - A curated target gene pool assisting disease prediction and patient-specific
      biomarker selection for lung squamous cell carcinoma.
AB  - There have been hundreds of genes demonstrated to be associated with lung
      squamous cell carcinoma (LSCC), presenting various degrees of association with
      this disease. In the present study, gene vectors were investigated as genetic
      biomarkers for the diagnosis and personalized treatment of LSCC. A LSCC genetic
      database (LSCC_GD) was developed through literature-associated data analysis,
      where 260 LSCC target genes were curated. Subsequently, numerous associations
      between these genes and LSCC were studied. Following this, a sparse
      representation-based variable selection (SRVS) was employed for gene selection
      from two LSCC gene expression datasets, followed by a case/control
      classification. Results were compared using analysis of variance (ANOVA)-based
      gene selection approaches. Using SRVS, a gene vector was selected from each
      dataset, resulting in significantly higher classification accuracy (CR), compared
      with randomly selected genes (For datasets GSE18842 and GSE1987, CR=100 and 100%
      and permutation P=5.0*10-4 and 1.8*10-3, respectively). The SRVS method
      outperformed ANOVA in terms of the classification ratio. The results indicated
      that, for a given dataset, there may be a gene vector from the 260 curated LSCC
      genes that possesses significant prediction power. SRVS is effective in
      identifying the optimum gene subset target for personalized treatment.

PMID- 30197683
TI  - MicroRNA-146a-5p enhances ginsenoside Rh2-induced anti-proliferation and the
      apoptosis of the human liver cancer cell line HepG2.
AB  - Liver cancer is one of the leading causes of malignancy-associated mortality
      worldwide and its clinical therapy remains very challenging. Ginsenoside Rh2
      (Rh2) has been reported to have antitumor effects on some types of cancer,
      including liver cancer. However, its regulatory mechanism has not been
      extensively evaluated. In the present study, Rh2 increased the expression of
      microRNA (miR)-200b-5p, miR-224-3p and miR-146a-5p, and decreased the expression
      of miR-26b-3p and miR-29a-5p. Of the three upregulated miRs, miR-146a-5p
      exhibited the highest fold elevation. In accordance with a previous study, Rh2
      effectively inhibited the survival of liver cancer cells in vitro and in a mouse
      model. In addition, it was observed that Rh2 markedly promoted liver cancer
      apoptosis and inhibited colony formation. Cell apoptosis and the inhibition of
      cell survival as well as colony formation induced by Rh2 were enhanced and
      weakened by miR-146a-5p overexpression and inhibition, respectively. The results
      of the present study provide further evidence of the antitumor effect of Rh2 in
      liver cancer and also demonstrate that this effect may be mediated via the
      regulation of miR-146a-5p expression in the liver cancer cell line HepG2. The
      results indicated that miR-146a-5p may be a promising regulatory factor in Rh2
      mediated effects in liver cancer.

PMID- 30197684
TI  - Near-infrared spectroscopy muscle oximetry of patients with postural orthostatic
      tachycardia syndrome.
AB  - Postural orthostatic tachycardia syndrome (POTS) is a disabling condition
      characterized by orthostatic intolerance with tachycardia in the absence of drop
      in blood pressure. A custom-built near-infrared spectroscopy device (NIRS) is
      applied to monitor the muscle oxygenation, noninvasively in patients undergoing
      incremental head-up tilt table (HUT). Subjects (6 POTS patients and 6 healthy
      controls) underwent 30 mins of 70 degrees on a HUT. The results showed a
      significant difference in deoxyhemoglobin (Hb), change-in-oxygenation (DeltaOxy)
      and blood volume (DeltaBV) between patients and healthy controls. However,
      oxyhemoglobin (HbO2) showed a significantly faster rate of change in the healthy
      controls during the first 10 mins of the tilt and during the recovery. This NIRS
      muscle oximetry tool provides quantitative measurements of blood oxygenation
      monitoring in diseases such as POTS.

PMID- 30197686
TI  - Sequence-Based In-silico Discovery, Characterisation, and Biocatalytic
      Application of a Set of Imine Reductases.
AB  - Imine reductases (IREDs) have recently become a primary focus of research in
      biocatalysis, complementing other classes of amine-forming enzymes such as
      transaminases and amine dehydrogenases. Following in the footsteps of other
      research groups, we have established a set of IRED biocatalysts by sequence-based
      in silico enzyme discovery. In this study, we present basic characterisation data
      for these novel IREDs and explore their activity and stereoselectivity using a
      panel of structurally diverse cyclic imines as substrates. Specific activities of
      >1 U/mg and excellent stereoselectivities (ee>99 %) were observed in many cases,
      and the enzymes proved surprisingly tolerant towards elevated substrate loadings.
      Co-expression of the IREDs with an alcohol dehydrogenase for cofactor
      regeneration led to whole-cell biocatalysts capable of efficiently reducing
      imines at 100 mM initial concentration with no need for the addition of
      extracellular nicotinamide cofactor. Preparative biotransformations on gram scale
      using these 'designer cells' afforded chiral amines in good yield and excellent
      optical purity.

PMID- 30197687
TI  - Closing yield gaps in smallholder goat production systems in Ethiopia and India.
AB  - Small ruminants such as goats are an important source of income for smallholder
      farmers in South Asia and Sub Saharan Africa: they may be kept as a stepping
      stone to owning larger and higher-value animals such as cattle or buffalo, or
      provide a more-profitable and less-risky alternative in marginal or densely
      populated areas where access to feed resources are limited. However, smallholder
      goat production in these areas is often low due to low growth and reproduction
      rates and high animal mortality. The aim of this study was to investigate the
      potential for different intervention packages to increase yields and
      profitability of goat meat production in Ethiopia and India. Packages were based
      on improved nutrition, reduced flock mortality from improved control of health
      and diseases, and replacing indigenous livestock with improved goat breeds.
      Household modelling was used to simulate the effects of interventions on goat
      production and household income in the extensive lowland grazing zone and
      highland mixed crop-livestock zones of Ethiopia, and the extensive arid zone of
      India. Our analysis showed that there are opportunities to increase goat meat
      production in both countries. Reproduction, liveweight gain and survival rates
      can be increased through better nutrition, genetics and healthcare, but the
      biggest increase in production and profits occurred when multiple interventions
      were combined. Importantly, interventions resulting in the biggest increases in
      goat meat production or number of animals sold did not always give the highest
      profits.

PMID- 30197685
TI  - Meta-analysis of Mobile Phone Reminders on HIV Patients' Retention to Care.
AB  - Aims: This research aims to systematically review the current clinical evidence
      of the efficacy of mobile phone reminders on retention to care among HIV
      patients. This study also seeks to determine an effect size of the intervention
      and presents implications for future studies. Background: Use of mobile
      technologies is an innovative and affordable approach to HIV prevention and care,
      particularly in resource limited settings. Approximately two-thirds of people who
      are initially diagnosed with HIV are lost to follow-up before starting HIV
      treatment in low and middle-income countries, posing serious global health
      concerns. While mobile text message reminders for HIV medication adherence have
      shown positive health outcomes, it is not well understood whether the reminders
      can also improve patients' retention to care. Methods: The authors conducted a
      meta-analysis of literature in the following databases: PubMed, CINAHL, ProQuest,
      and Web of Science. Of the 667 peer-reviewed research articles reviewed, nine
      studies were included in the final analysis. Stata version 13 was used for the
      analysis. Results: Nine studies (5 randomized controlled and 4 before and after
      studies) from 7 countries included 3,004 HIV patients. Random-effect meta
      analysis (I-squared = 94.1%) found that HIV patients who received mobile phone
      reminders for their follow-up appointments were two times more likely to return
      to care than those who didn't receive reminders (pooled odd ratio (OR)=2.04, 95%
      CI: 0.97-4.27). Our sub-group analysis of 5 randomized controlled studies showed
      a significant effect of mobile phone reminders (OR=2.04, 95% CI: 1.11-3.74). Six
      studies in Africa showed that HIV patients (mostly women) receiving mobile phone
      reminders were three times more likely to return to care than those who received
      no reminders (OR=2.92, 95% CI: 1.13-7.53). Conclusion: Mobile phone reminders are
      an effective intervention to improve retention to HIV care. Women with HIV living
      in resource limited settings benefit significantly from the intervention. Also,
      mobile phone reminders using text messages are as effective as phone calls to
      improve retention to HIV care.

PMID- 30197688
TI  - RpbL12 Assists Catalysis by Correctly Positioning the Incoming Aminoacyl-tRNA in
      the A-Site of E. coli 70S Ribosomes.
AB  - Introduction: We have recently demonstrated that Lys-65 of the 62GANK65 motif of
      E. coli RpbL12 was affinity labeled with a tRNA analogue, resulting in the loss
      of activity. Materials and Methods: In this report, we show that mutations
      operated at the position of Lys-65 led to an impairment in the activity of the
      mutant ribosomes, except the K65R or K65H bL12 mutants, suggesting that the only
      requirement of the reaction catalyzed or facilitated by RpbL12is the positive
      charge of the side chain of Lys-65. We also demonstrate that Lys-65 did not play
      any role in the peptidyl transferase reaction with respect to puromycin, but
      rather assisted the binding of the incoming aminoacyl-tRNA to the ribosomal A
      site. Results & Discussions: The protonated, positively charged epsilonNH3+ form
      of Lys-65 is likely to participate to the binding of aa-tRNA through ionic bonds
      with phosphate groups, in order to insure the accurate positioning required for
      the nucleophilic attack of its alpha-amino group on the carbonyl carbone of
      peptidyl-tRNA. Conclusion: This alpha-NH2 group is likely to be generated by the
      unprotonated epsilonNH2 form of Lys-65 which is capable of withdrawing a proton
      from the alpha-NH3+ group of aa-tRNA.

PMID- 30197689
TI  - The Effect of Flat Dual-Cure Stabilizer Occlusal Splint in Pain Relief of
      Individuals Suffering from Migraine Headaches.
AB  - Background: No study on the effect of dual-cure stabilizer splint without canine
      ramp in migraine patients is present. Objective: This study was conducted to
      determine the effects of maxillary flat dual-cure stabilizer occlusal splint on
      severity, frequency and episodes of headaches in individuals suffering from a
      migraine. Methods: In this interventional clinical trial, 30 eligible patients
      were divided into 2 groups (case and control); each group consisted of 8 men and
      7 women. Dual-cure stabilizer splint was made for patients in the case group and
      they used the adjusted splint 20 hours a day for 6 weeks. The severity, frequency
      and episodes of migraine attacks before and after using the splint were
      determined. For grading pain, severity visual analogue scale was used. The data
      were analyzed using SPSS 20 and Kolmogorov-Smirnov test and paired t-test.
      Results: The severity, frequency, and episodes of migraine attacks before and
      after using the splint were reduced by 56%, 68%, and 72%, respectively. The
      reduction was statistically significant (p < 0.05). Discussion: Despite the
      effect of occlusal devices on the migraine disorder is controversial, the most
      researchers agree that using these appliances can be effective in reducing
      headache in migraine patients. Conclusion: Given the favorable effects of dual
      cure stabilizer splint on reducing the severity, frequency and episodes of
      migraine headaches, the device can be used as an effective alternative therapy
      besides common pain-relieving methods.

PMID- 30197690
TI  - The Association between Ponticulus Posticus and Dental Agenesis: A Retrospective
      Study.
AB  - Objective: Neural tube defects may increase the risk of an abnormal development
      of skull, vertebral column and teeth formation, including dental agenesis in non
      syndromic patients. The association between the presence of a congenital Dental
      Agenesis (DA) and the Atlantooccipital Ligament (AOL) calcification, known as
      "Ponticulus Posticus" (PP), as possible links can be investigated. Design: After
      a systematic review of the scientific literature on this topic, two independent
      examiners assessed the AOL calcification in lateral cephalograms of 350 non
      syndromic patients(7-21 years old). The results were compared with a control
      group (non syndromic patients, without congenital missing teeth). Results: The
      16.3% of the population studied by cephalometric analysis revealed a prevalence
      rate of PP (both complete and partial) with a slight male predominance is seen,
      not statistically significant (chi square test = 0.09; p= 0.76). In both sexes
      complete PP is more observed. In the patients affected by DA the frequency of PP
      is the 66.6% (both complete than partial). The chi square test with Yates
      correction showed a significative difference(chi= 66.20; p value= 0.00) between
      PP in patients with DA compared to not affected by DA. Conclusions: PP is not an
      uncommon anomaly. Since orofacial pain like migraine and other symptoms are often
      associated to PP, during routine radiographic examination, if detected, it should
      be documented in patients' health record and with symptoms, further investigation
      should be sought for. These findings encourage to think there's an association
      between DA in non syndromic patients and neuro-crestal cells defects.

PMID- 30197691
TI  - The Periodontium as a Potential Cause of Orofacial Pain: A Comprehensive Review.
AB  - Introduction: Orofacial pain of periodontal origin has a wide range of causes,
      and its high prevalence and negative effect on patients' quality of life make
      intervention mandatory. This review provides a periodontological overview of the
      field of orofacial pain, focusing on the entities which involve the periodontal
      tissues and may be the cause of this pain or discomfort. Methods: The study
      comprised a literature search of these pathologies conducted in the
      MEDLINE/PubMed Database. Acute infectious entities such as gingival and
      periodontal abscesses are emergencies that require a rapid response.
      Periodontitis associated with endodontic processes, necrotizing periodontal
      disorders, desquamative gingivitis, gingival recession, and mucogingival herpetic
      lesions, cause mild to severe pain due to tissue destruction and loss. Other
      lesions that lead to periodontal discomfort include gingival enlargement and
      periodontal ligament strains associated with occlusal trauma, parafunctional
      habit and the impaction of food or foreign bodies. Conclusion: A range of
      therapeutic, pharmacological and surgical alternatives are available for the
      management of these injuries. However, the wide variety of causes of orofacial
      pain or periodontal discomfort may confuse the clinician during diagnosis and may
      lead to the wrong choice of treatment.

PMID- 30197692
TI  - Peri-Implant Bone Loss at Implants Placed in Preserved Alveolar Bone Versus
      Implants Placed in Native Bone: A Retrospective Radiographic Study.
AB  - Objectives: The aim of our study was to compare peri-implant bone loss at
      implants placed in alveolar sockets filled with a particulate allogenous bone
      graft (DFDBA 300-500 um) and platelet concentrates versus at implants placed in
      the native bone. Materials and Methods: A retrospective clinical study was
      performed. A total of 84 patients were included with 247 implants for the
      restoration of mono and pluri-radicular teeth: 169 implants in native bone and 78
      in socket-grafted bone. The peri-implant bone loss was measured by 2 independent
      operators at 6 and 12 months. Results: The overall mesial and distal peri-implant
      bone losses were 0.9 +/- 0.7 mm and 0.9 +/- 0.8 mm at 6 months, respectively, and
      1 +/- 0.65 mm and 1.2 +/- 0.9 mm at 12 months, respectively. In the tested group,
      the bone loss was 0.8 +/- 0.8 mm at 6 months and 1.2 +/- 0.9 mm at 12 months. In
      the control group, the bone loss was 1.0 +/- 0.7 mm at 6 months and 0.95 +/- 0.6
      mm at 12 months. There were no statistically significant differences in bone loss
      between the two groups. Taking both groups together, there were no statistically
      significant difference in bone loss between patients with or without histories of
      periodontitis, but there was a statistically significant difference in bone loss
      between the mandible and maxilla as well as between unitary and total edentations
      and between partially and total edentulous patients. Conclusion: At 6 and 12
      months, the peri-implant bone loss in sockets preserved with DFDBA and platelet
      concentrates was similar to the peri-implant bone loss in native bone.

PMID- 30197693
TI  - Evaluation of Effect of Low-Dose Methotrexate on Osseointegration of Implants: A
      Biomechanical Study on Dogs.
AB  - Background: Methotrexate (MTX) is an immunosuppressive drug, widely used in
      inflammatory disturbances including rheumatoid arthritis. However, there is no
      consensus regarding the effect of MTX on implant osseointegration. Objective: The
      purpose of this experimental study was to investigate the effect of low dose MTX
      on Bone-Implant Contact (BIC) of dogs. Methods: Six mandibular premolar teeth
      (bilateral) of 8 mature dogs were extracted. After 3 months of healing, 6
      implants (bone level, resorbable blast media surface) were inserted into the
      mandible of each dog (3 in each side). Dogs were randomly divided into a study
      group (receiving 2.5 mg/week MTX orally, 3 times per week for 4 weeks) and a
      control group each containing 4 dogs. In the 1st week, postoperative BIC was
      evaluated in 4 dogs, two from each group. In the 4th week, reverse torque and BIC
      were evaluated in the remaining 4 dogs. Data were analyzed with two-way ANOVA
      test for 95% confidence interval. Results: The reverse torque test of the 4th
      week, showed a satisfying osseointegration. Histopathologic evaluation revealed
      that the BIC was significantly higher in the control group in comparison to the
      MTX group in the 1st and 4th week. In addition, the BIC of both groups were
      significantly increased in the 4th week in comparison to the 1st week in both
      groups. Conclusion: MTX has the potential to interfere with osseointegration
      process.

PMID- 30197694
TI  - Influence of Time Intervals between Bleaching Procedures on Enamel Microhardness
      and Surface Roughness.
AB  - Background: Dental bleaching has been increasingly sought out to improve dental
      aesthetics, but it may cause changes in dental enamel. Objective: To assess the
      influence of different time intervals on bleaching gel applications with regard
      to the Microhardness (MH) and Surface Roughness (SR) on dental enamel. Material
      and Methods: Forty bovine incisors were randomly divided into two groups (G1 and
      G2) and both were bleached with 35% Hydrogen Peroxide (HP35) (n=20; G1: seven-day
      interval and G2: two-day interval). The MH and SR tests were performed before
      bleaching (T0) and after the first (T1), second (T2), and third (T3) bleaching
      gel applications. The specimens were stored in artificial saliva between each
      application (37 degrees C). The data were analyzed using the student's t-test (p
      <= 0.05) for dependent samples. Results: The reduced time interval (two days) led
      to a significant reduction in MH, while MH was not affected during the seven-day
      interval. The SR results increased regardless of the bleaching gel application
      time interval. Conclusion: The decreased time interval of two days between
      bleaching gel applications caused changes in MH but did not influence the SR of
      dental enamel.

PMID- 30197695
TI  - Purification of Stem Cells from Oral Pyogenic Granuloma Tissue.
AB  - Introduction: The isolation of stem cells from pathologically damaged dental
      tissues has been examined only by a few studies. The purpose of this study was to
      evaluate the possibility of isolation of stem cells from pyogenic granuloma.
      Methods: Pyogenic granuloma tissues were enzymatically digested and the resulting
      single cells were cultured. Then, the cultured cells differentiated into
      adipocytes and osteoblasts cells. Flow cytometry analyses were performed on
      markers such as CD 90, CD 73, CD105, CD 45 and CD14. Other features were also
      analyzed including the effect of colony formation and potentials of
      differentiation into adipocytes and osteoblasts. Results: The cells derived from
      pyogenic granuloma tissue formed higher colonies similar to typical spindle
      shaped fibroblasts. The cells were positive for mesenchymal markers such as CD
      44, CD 271, CD 90, and CD 73, and negative for surface molecules such as CD 14,
      CD 34 and CD 45. Moreover, they successfully differentiated into adipocytes and
      osteoblasts. Conclusion: The cells isolated from pyogenic granuloma could form
      CFU fibroblastic units expressing an appropriate marker panel of the cell surface
      antigen and adequate differentiation potential, all of which met the Cell Therapy
      International Association criteria for the definition of mesenchymal stromal
      cells. Pyogenic granuloma contains cells with stem cell properties.

PMID- 30197696
TI  - Microbial Infections and Antimicrobial Resistance in Nepal: Current Trends and
      Recommendations.
AB  - Antimicrobial resistance is a life threatening challenges to the world. Most of
      the well-known antibiotics are currently ineffective to several microbial
      diseases. Ampicillin, metronidazole, amoxicillin, cotrimoxazole, chloramphenicol,
      ciprofloxacin, nalidixic acid, gentamicin, and ceftazidime are common antibiotics
      whose resistance pattern has been elevated in recent years. The rise and
      dissemination of resistant bacteria has contributed in increasing cases of
      antimicrobial resistance. Multi-drug Resistant (MDR) organism such as
      Staphylococcus aureus, Pseudomionas aeruginosa, Escherchia coli, and
      Mycobacterium tuberculosis are principal problems for public health and
      stakeholders. Globally, issues of antimicrobial resistance are major concern. In
      the context of Nepal, insufficient surveillance system, lack of appropriate
      policy, and poor publications regarding the use of antibiotics and its resistance
      pattern has misled to depict exact scenario of antimicrobial resistance. This
      mini-review presents current trends of antibiotic use and its resistance pattern
      in Nepal. In addition, global progression of antibiotic discovery and its
      resistance has been covered as well. Furthermore, use of antibiotics and possible
      ways on improvement of effectiveness have been discussed.

PMID- 30197697
TI  - Nontypable Haemophilus influenzae Septicemia and Urinary Tract Infection
      Associated with Renal Stone Disease.
AB  - Introduction: Haemophilus influenzae commonly causes upper respiratory tract
      infections and has only rarely been reported etiology of urinary tract
      infections. Since the introduction of the Haemophilus influenzae b (Hib) vaccine,
      non-typable haemophilus species now cause the majority of invasive disease in
      Europe. Case Report: We report a case of an adult man with non-typable
      Haemophilus influenzae septicemia, urinary tract infection and bilateral renal
      stone disease. The patient presented with right sided flank pain and a CT scan
      showed bilateral renal stones and a right sided ureteral stone causing
      obstruction. Results and Discussion: Haemophilus influenzae was identified in
      blood and urine and despite a tendency of increasing antibiotic resistance among
      Haemophilus influenzae, our strain was susceptible to all antibiotics tested.
      Treatment consisted of 3 days of intravenous cefuroxime, insertion of a right
      sided JJ ureteric stent and 5 days of peroral ciprofloxacin after discharge.
      Physicians and microbiologists should be aware of Haemophilus influenzae as a
      possible urinary tract pathogen, especially when urinary tract abnormalities are
      present, and take the risk of antibiotic resistance into consideration at initial
      treatment.

PMID- 30197698
TI  - Detection of Plasmid-Mediated qnr Genes Among the Clinical Quinolone-Resistant
      Escherichia coli Strains Isolated in Tehran, Iran.
AB  - Background: Escherichia coli is one of the most important bacterial agents to
      cause urinary tract infections. Inappropriate and unnecessary administration of
      antibiotics has led to an increase in the appearance of multidrug-resistant E.
      coli isolates, limiting treatment options. The increase in a number of resistant
      strains of bacteria is a major concern of health authorities worldwide.
      Objective: The purpose of this study was to determine the presence of the qnr
      genes among E. coli isolated from UTIs of patients in Baqiyatallah hospital in
      Tehran province, Iran. Method: Clinical urine samples of patients with suspected
      urinary tract infection were collected by standard methods in sterile disposable
      containers. After analysis of urine, microscopic observations and culture
      analysis, the bacterial genome was extracted by boiling method. PCR for detection
      of qnr genes including qnrA, qnrB and qnrS was done by specific primers, then PCR
      products were run using gel electrophoresis and visualized by gel documentation
      system. Results: In the present study among the 95 isolates, 60 strains were
      resistant to nalidixic acid. PCR showed that 92 strains were positive for qnrS.
      The qnrA and qnrB genes were not found among the clinical isolates. Conclusion:
      Our finding indicates a high level of resistance against nalidixic acid among E.
      coli isolates recovered from the patients with UTI. Also, the high frequency of
      qnrS imposes the importance of survey of molecular and genetic analysis of
      mechanisms of quinolone resistance in E. coli strains.

PMID- 30197699
TI  - The Frequency of Antibiotic Resistance and ESBLs Among Clinically Acinetobacter
      baumannii Strains Isolated from Patients in a Major Hospital in Tehran, Iran.
AB  - Background: Bacterial resistance to antibiotics limits treatment options,
      increases morbidity and mortality, and raises the risk of antibiotic-associated
      adverse events. Antibacterial resistance emerges rapidly following an increase in
      the consumption of antibiotics against infectious diseases. The spread of ESBL
      producing strains has a limiting factor based on antibiotic function for the
      treatment of infections particularly caused by Acinetobacter baumannii (A.
      baumannii). Objective: This study was conducted to evaluate the prevalence of
      antimicrobial resistance and distribution of blaTEM , blaCTX , and blaSHV genes
      among A. baumannii strains isolated from clinical samples at a major hospital in
      Teheran, Iran. Methods: A. baumannii strains were isolated and identified using
      standard microbiological methods. The disc diffusion and combined discs methods
      were used for testing antimicrobial susceptibility and to identify the strains
      producing Extended-Spectrum Beta-Lactamases (ESBL), respectively. DNA extraction
      was done by boiling method. Finally, the frequency of resistant genes including
      blaTEM , blaCTX , and blaSHV in ESBL producing isolates was studied by PCR.
      Results: Gender distribution in this study was 53 (53%) samples for men and 47
      (47%) for women. Totally, one hundred A. baumannii strains were isolated. More
      than 93% of the isolates were multi drug resistant. The highest to lowest
      antibiotic resistance was observed against amoxicillin/clavulanic acid (98%),
      ceftriaxone (96%), cefotaxime (94%), and ceftazidime (93%), respectively. The
      frequency of positive phenotypic test of ESBL was 19% and 16% for CAZ-C and CTX
      C, respectively. The frequency of blaTEM , blaCTX , and blaSHV genes was 52.1,
      43.4, and 21.7, respectively. Conclusion: A. baumannii isolates exhibited an
      extremely worrying level of antibiotic resistance, and a high percentage of the
      isolates showed MDR in this study. This is a serious warning because ESBLs are a
      major threat to the effectiveness of antibiotics that are currently available for
      medical uses. The frequency of genes encoded ESBL isolates of A. baumannii may be
      due to overuse and misuse of antibiotics.

PMID- 30197701
TI  - Functional Exploration Of T-Type Calcium Channels (Cav3.2 And Cav3.3) And Their
      Sensitivity To Zinc.
AB  - Introduction: T-type Ca2+ channels (TTCC) are low Voltage-gated calcium channels,
      expressed in various tissues such as the brain and heart, and contribute to a
      variety of physiological functions including neuronal excitability, hormone
      secretion, muscle contraction, and pacemaker activity. At high concentrations,
      Zinc (Zn2+) is naturally attached to cell membranes and is therefore considered a
      reversible inhibitor of calcium. Zinc is also involved in the kinetics of sodium
      and potassium currents. Zinc is essential for many functions. A low zinc tenor is
      associated with emotional instability, digestive disorders, slow-growing and
      alteration of protein synthesis. Material and Methods: For the Cell Culture we
      used HEK-293/tsA-201, and for transfection, the pCDNA3 plasmid constructs
      encoding human CaV3.2, and CaV3.3 subunits. Electrophysiological experiments were
      performed using the whole cell configuration of the patch-clamp technique. T-type
      currents were recorded using a test pulse from a holding potential at (-100mV) to
      (-30 mV), data Acquisition and Analysis for Current-voltage relationships (I-V
      curves) were recorded for the two cloned T-type Ca2+ channels (Cav3.2, Cav3.3).
      Results: Our studies describe the behavior of these channels Cav3.2 and Cav3.3
      and also their current sensitivity to Zinc (Zn2+) in transfected HEK-293/tsA
      201cells. Our results show that Zn2+ applies a modulatory effect on T-type
      calcium channels. We observe that Zn2+ differentially modulates the CaV3.2 and
      CaV3.3 channels. Zn2+ preferably inhibits Cav3.2. Conclusion: We have
      demonstrated that Zn2+ differentially modulates two CaV3 channels (Cav3.2 and
      Cav3.3): It is a preferential blocker of CaV3.2 channels and it alters the gating
      behaviour of CaV3.3 channels.

PMID- 30197700
TI  - Below-ground-above-ground Plant-microbial Interactions: Focusing on Soybean,
      Rhizobacteria and Mycorrhizal Fungi.
AB  - Introduction: Organisms seldom exist in isolation and are usually involved in
      interactions with several hosts and these interactions in conjunction with the
      physicochemical parameters of the soil affect plant growth and development.
      Researches into below and aboveground microbial community are unveiling a myriad
      of intriguing interactions within the rhizosphere, and many of the interactions
      are facilitated by exudates that are secreted by plants roots. These interactions
      can be harnessed for beneficial use in agriculture to enhance crop productivity
      especially in semi-arid and arid environments. The Rhizosphere: The rhizosphere
      is the region of soil close to plants roots that contain large number of diverse
      organisms. Examples of microbial candidates that are found in the rhizosphere
      include the Arbuscular Mycorrhizal Fungi (AMF) and rhizobacteria. These
      rhizosphere microorganisms use plant root secretions such as mucilage and
      flavonoids which are able to influence their diversity and function and also
      enhance their potential to colonize plants root. Natural Interactions between
      Microorganisms and Plant: In the natural environments, plants live in
      interactions with different microorganisms, which thrive belowground in the
      rhizosphere and aboveground in the phyllosphere. Some of the plant-microbial
      interactions (which can be in the form of antagonism, amensalism, parasitism and
      symbiosis) protect the host plants against detrimental microbial and non
      microbial invaders and provide nutrients for plants while others negatively
      affect plants. These interactions can influence below-ground-above-ground plants'
      biomass development thereby playing significant role in sustaining plants.
      Therefore, understanding microbial interactions within the rhizosphere and
      phyllosphere is urgent towards farming practices that are less dependent on
      conventional chemical fertilizers, which have known negative impacts on the
      environments. Below Ground Rhizobacteria Interactions Alleviate Drought Stress:
      Drought stress is one of the major factors militating against agricultural
      productivity globally and is likely to further increase. Belowground
      rhizobacteria interactions could play important role in alleviating drought
      stress in plants. These beneficial rhizobacterial colonize the rhizosphere of
      plants and impart drought tolerance by up regulation or down regulation of
      drought responsive genes such as ascorbate peroxidase, S-adenosyl-methionine
      synthetase, and heat shock protein. Insights into Below and above the Ground
      Microbial Interactions via Omic Studies: Investigating complex microbial
      community in the environment is a big challenge. Therefore, omic studies of
      microorganisms that inhabit the rhizosphere are important since this is where
      most plant-microbial interactions occur. One of the aims of this review is not to
      give detailed account of all the present omic techniques, but instead to
      highlight the current omic techniques that can possibly lead to detection of
      novel genes and their respective proteins within the rhizosphere which may be of
      significance in enhancing crop plants (such as soybean) productivity especially
      in semi-arid and arid environments. Future Prospects and Conclusions: Plant
      microbial interactions are not totally understood, and there is, therefore, the
      need for further studies on these interactions in order to get more insights that
      may be useful in sustainable agricultural development. With the emergence of omic
      techniques, it is now possible to effectively monitor transformations in
      rhizosphere microbial community together with their effects on plant development.
      This may pave way for scientists to discover new microbial species that will
      interact effectively with plants. Such microbial species can be used as
      biofertilizers and/or bio-pesticides to increase crop yield and enhance global
      food security.

PMID- 30197702
TI  - The Effect of Comprehensive Medical Care on the Long-Term Outcomes of Children
      Discharged from the NICU with Tracheostomy.
AB  - Background: Survival of infants with complex care has led to a growing population
      of technology-dependent children. Medical technology introduces additional
      complexity to patient care. Outcomes after NICU discharge comparing Usual Care
      (UC) with Comprehensive Care (CC) remain elusive. Objective: To compare the
      outcomes of technology-dependent infants discharged from NICU with tracheostomy
      following UC versus CC. Methods: A single site retrospective study evaluated
      forty-three (N=43) technology-dependent infants discharged from NICU with
      tracheostomy over 51/2 years (2011-2017). CC provided 24-hour accessible
      healthcare-providers using an enhanced medical home. Mortality, total hospital
      admissions, 30-days readmission rate, time-to-mechanical ventilation liberation,
      and time-to-decannulation were compared between groups. Results: CC group showed
      significantly lower mortality (3.4%) versus UC (35.7%), RR, 0.09 [95%CI, 0.12
      0.75], P=0.025. CC reduced total hospital admissions to 78 per 100 child-years
      versus 162 for UC; RR, 0.48 [95% CI, 0.25-0.93], P=0.03. The 30-day readmission
      rate was 21% compared to 36% in UC; RR, 0.58 [95% CI, 0.21-1.58], P=0.29). In
      competing-risk regression analysis (treating death as a competing-risk), hazard
      of having mechanical ventilation removal in CC was two times higher than UC; SHR,
      2.19 [95% CI, 0.70-6.84]. There was no difference in time-to-decannulation
      between groups; SHR, 1.09 [95% CI, 0.37-3.15]. Conclusion: CC significantly
      decreased mortality, total number of hospital admissions and length of time-to
      mechanical ventilation liberation.

PMID- 30197704
TI  - Immune Regulatory Genes Are Major Genetic Factors to Behcet Disease: Systematic
      Review.

PMID- 30197705
TI  - Comparison of Vitamin D Serum Values between Rheumatoid Arthritis and Lupus
      Populations: An Observational Study.

PMID- 30197703
TI  - MicroRNA155 Expression in Relation to BDCAF Scored Behcet's Disease in an
      Egyptian Patients' Sample.
AB  - Objective: To discover the possibility of using microRNA155 (miRNA155) expression
      level as a biomarker of Behcet's Disease (BD) activity or remission. Methods:
      Thirty BD patients' white blood cells (WBCs) miRNA155 expression was measured and
      compared to WBCs miRNA155 expression in 15 healthy subjects. Assessment of
      disease activity was done using Behcet's Disease Current Activity Form (BDCAF).
      Results: miRNA155 expression significantly decreases with the increase of BD
      activity scored by BDCAF. Conclusion: Increased miRNA155 may be used as a
      biomarker of BD remission and thus in the disease follow up. There could be a
      prospect of treating the disease via microRNA 155 effect enhancement.

PMID- 30197706
TI  - Pamidronate Treatment of Osteonecrosis of the Hip in Young Male.
AB  - Background: Aseptic osteonecrosis of the hip is a clinical entity in which the
      necrotic process of the bone leads to pain and progressive disability. Objective:
      Pamidronate seems to reduce drastically the activation of the osteoclasts so that
      it can be useful only in the early stage of the disease, delaying the time of
      bone collapsing. Method: A 27-years-old male was treated with pamidronate for
      three consecutive days every four weeks. Results: After three months the patient
      came back at control showing a marked improvement in clinical condition, referred
      full recover from pain and dysmotility with improvement of the quality of life,
      which was confirmed by the result of MRI he had for control. Conclusion: We
      reported a case of aseptic osteonecrosis of the hip which was successfully
      treated pamidronate at dosage of 45 mg.

PMID- 30197707
TI  - Labral Repair Versus Biceps Tenotomy/Tenodesis for the Treatment of Type II SLAP
      Lesions: Indications and Technique.

PMID- 30197708
TI  - An Age and Activity Algorithm for Treatment of Type II SLAP Tears.
AB  - Background: Type II SLAP tears predominantly occur in males between their third
      and fifth decades of life. The mechanism of injury is often repeated overheard
      activity but can also occur due to direct compression loads and traction
      injuries. The treatment options have changed over the years and include non
      operative therapy, direct labral-biceps complex repair, and labral debridement
      with biceps tenodesis or tenotomy. Objective: To review the existing literature
      on the management of Type II SLAP tears and provide clinical recommendations
      based on patient age and activity level. Methods: A review of the existing
      literature through October 2017 investigating the management of Type II SLAP
      tears was performed. Emphasis was placed on distinguishing the outcomes based on
      age and activity level to provide an appropriate treatment algorithm. Results:
      Patients with Type II SLAP tears should first be trialed with non-operative
      management and many patients will have a successful result with ability to return
      to their respective sports or activities. Surgical management should be
      considered if non-operative management does not provide symptomatic relief.
      Young, athletic, or high-demand patients should be treated with a SLAP repair
      while biceps tenodesis should be considered for older or worker's compensation
      patients. Patients undergoing revision surgery for a failed SLAP repair should be
      managed with biceps tenodesis. Conclusion: Type II SLAP tears remain a difficult
      pathology to manage clinically, but the treatment indications are narrowing. The
      age and activity algorithm described in this review provides an effective method
      of managing this complex clinical condition.

PMID- 30197709
TI  - A Treatment-Based Algorithm for the Management of Type-II SLAP Tears.
AB  - Background: The management of Type-II superior labral tears (SLAP) of the
      shoulder remains a controversial topic. Treatment ranges from non-operative
      management to surgical management including SLAP repair, biceps tenotomy, and
      biceps tenodesis. An optimal treatment algorithm has yet to reach universal
      acceptance. Objective: The goal of this paper was to provide a treatment
      algorithm for the management of Type-II SLAP tears based on current literature
      and expert opinion. Method: Current literature was reviewed and expert opinion
      was reported to develop a comprehensive treatment protocol for patients based on
      age, activity level, and pathology. Results: Operative management of type-II SLAP
      tears yields good to excellent outcomes when proper indications are followed.
      Biceps tenodesis may produce more reliable pain relief and functional improvement
      when compared to primary SLAP repair in patients over the age of 40. Conclusion:
      When non-operative management of Type-II SLAP tears fails, operative management
      yields good to excellent outcomes in most patients. Primary SLAP repair should be
      performed in patients under the age of 40 with no evidence of proximal biceps
      pathology, while biceps tenodesis can provide consistent pain relief and return
      to activity in patients over the age of 40 or with significant proximal biceps
      pathology. Tenotomy should be reserved for elderly or low demand individuals.

PMID- 30197710
TI  - Treatment of SLAP Lesions.
AB  - Background: The surgical treatment of a Superior Labrum Anterior and Posterior
      (SLAP) lesion becomes more and more frequent as the surgical techniques, the
      implants and the postoperative rehabilitation of the patient are improved and
      provide in most cases an excellent outcome. Objective: However, a standard
      therapy of SLAP lesions in the shoulder surgery has not been established yet. An
      algorithm on how to treat SLAP lesions according to their type and data on the
      factors that influence the surgical outcome is essential for the everyday
      clinical practice. Method: In this article, a retrospective evaluation of
      patients with SLAP lesion, treated surgically in our orthopaedic clinic was
      conducted. Results: According to the clinical outcome and our experience with the
      surgical therapy of SLAP lesions we demonstrate an algorithm on the proper
      therapeutic approach. Conclusion: SLAP I lesions are treated with debridement.
      Most controversies concern patients with SLAP II lesions, whose therapy is either
      fixation of the superior labrum or tenotomy/tenodesis of the long head of the
      biceps tendon. For patients with SLAP III or IV lesions the most commonly
      accepted approach is tenotomy or tenodesis of the long head of biceps tendon.

PMID- 30197711
TI  - Superior Capsular Release After Failed Combined Superior Labral Repair And Biceps
      Tenodesis For Slap Tear.
AB  - Introduction: Optimal treatment of type II superior labrum anterior and posterior
      (SLAP) tears is controversial. There has been a recent trend towards biceps
      tenodesis over SLAP repair in older patients. Few surgeons have performed
      combined biceps tenodesis and SLAP repair with inferior results. Case Report:
      This case describes a 46-year-old patient who had persistent pain and stiffness
      after combined biceps tenodesis and SLAP repair for a type II SLAP tear. His pain
      and motion improved after arthroscopic superior capsular release. Conclusion:
      Failed SLAP repair is often multifactorial and a thorough workup is needed.
      Combined biceps tenodesis and SLAP repair can cause pain, stiffness, and
      dysfunction which can be successfully treated with arthroscopic superior capsular
      release.

PMID- 30197712
TI  - Superior Labral Anterior to Posterior Tear Management in Athletes.
AB  - Background: The diagnosis and treatment of Superior Labrum Anterior to Posterior
      (SLAP) tears have been evolving and controversial. The lack of clear diagnostic
      criteria on physical examination, Magnetic Resonance Imaging (MRI), and
      arthroscopic evaluation clouds the issue. The high rate of MRI diagnosed SLAP
      lesions in the asymptomatic population of athletes and non-athletes warrants
      consideration when planning treatment for those with shoulder pain. Objective: To
      provide information on the evaluation, diagnosis and management of SLAP tears in
      athletes. Methods: The results of a structured non-operative rehabilitation
      program are discussed and compared to traditional surgical techniques. The
      evolution of the author's treatment algorithm is presented. Results: The
      successful return to overhand throwing is more common with non-operative
      treatment than with surgical. Conclusion: A rehabilitation program focused on
      stretching the posterior capsule and correcting scapular posture is more
      successful than surgery for most throwers with SLAP lesions.

PMID- 30197713
TI  - MR Imaging of SLAP Lesions.
AB  - Background: SLAP lesions of the shoulder are challenging to diagnose by clinical
      means alone. Interpretation of MR images requires knowledge of the normal
      appearance of the labrum, its anatomical variants, and the characteristic
      patterns of SLAP lesions. In general, high signal extending anterior and
      posterior to the biceps anchor is the hallmark of SLAP lesions. Common diagnostic
      criteria for a SLAP lesion by MR or MR arthrography include the following:
      presence of a laterally curved, high signal intensity in the labrum on a coronal
      image, multiple or branching lines of high signal intensity in the superior
      labrum on a coronal image, full-thickness detachment with irregularly marginated
      high signal intensity and/or separation >2 mm on conventional MRI or 3 mm on MR
      arthrography between the labrum and glenoid on a coronal image, and a paralabral
      cyst extending from the superior labrum. Methods: MR diagnosis of SLAP tears may
      be improved with provocative maneuvers, such as longitudinal traction of the arm
      or positioning of the shoulder in abduction and external rotation during imaging.
      The use of intra-articular contrast distends the joint similar to what occurs
      during arthroscopy and forced diffusion under the labrum may improve the ability
      to detect SLAP lesions that might not be seen with standard MR. Improved
      diagnostic accuracy for SLAP tears is seen with 3-T compared with 1.5-T MR
      imaging, with or without intra-articular contrast material. Conclusion:
      Regardless of MR findings, however, physicians should be cautious when
      recommending surgery in the patient with a vague clinical picture. The patient's
      history, physical exam, and imaging evaluation all should be considered together
      in making the decision to proceed with surgery.

PMID- 30197714
TI  - Treatment of Type Two Slap Lesion With Anatomic Suture Anchor Repair Without
      Biceps Tenotomy Or Tenodesis.
AB  - Background: Poor results after repair of type 2 SLAP tears are relatively common
      and some have reported better results after biceps tenodesis or tenotomy than
      repair. In addition, some believe that the long head of the biceps is expendable.
      Therefore, many now favor biceps tenotomy or tenodesis over biceps anchor repair
      either in all patients or in older patients, reserving SLAP lesion repair only
      for young athletes. Hypothesis: We hypothesized that repair of the biceps anchor
      of the labrum would be effective in all patients regardless of age provided that
      care was taken not to overtighten the labrum and that rotator cuff pain as the
      primary pain generator had been ruled out. Methods: All patients with type 2 SLAP
      lesion repair by the senior author since he began repairing them with suture
      anchors were prospectively evaluated. Patients with more than one other
      concomitant procedure, simultaneous rotator cuff repair or worker's compensation
      status were excluded. Results: 77% of patients were available for minimum two
      year followup. No patient had subsequent surgery or manipulation under anesthesis
      as a result of their SLAP repair. Standardized shoulder test score increased by 4
      points. Mean SANE score decreased from 53 pre-op to 14 post-op. Results were the
      same in those over versus under 40 years of age. Conclusion: Anatomic repair of
      Type 2 SLAP lesions at the biceps anchor without biceps tenodesis or tenotomy can
      produce good results in patients of all ages.

PMID- 30197716
TI  - SLAP lesions, An Opinion Piece.
AB  - SLAP lesions were first classified by Snyder in 1990. Results of treatment have
      been controversial without clear consensus. All have agreed that prospective
      studies would be useful. We conducted such a study between 2008 to 2114 that
      randomized treatment between sham surgery, biceps tenodesis and labral repair. No
      significant differences in results between the groups were found. Crossover
      between groups was only possible from the sham surgery group and this may
      introduce some degree of bias. However, the six month outcomes between all three
      groups before any crossover were statistically identical. Our results also do not
      favor biceps tenodesis versus SLAP repair when surgery is performed. Based on
      these results we have narrowed our indications for SLAP lesion surgery. We still
      treat some SLAP lesions surgically and individualize our treatment in each such
      cases. Most SLAP lesion patients, however, are ultimately treated non
      operatively.

PMID- 30197715
TI  - Current Concepts in the Evaluation and Management of Type II Superior Labral
      Lesions of the Shoulder.
AB  - Background: Superior labrum tears extending from anterior to posterior (SLAP
      lesion) are a cause of significant shoulder pain and disability. Management for
      these lesions is not standardized. There are no clear guidelines for surgical
      versus non-surgical treatment, and if surgery is pursued there are controversies
      regarding SLAP repair versus biceps tenotomy/tenodesis. Objective: This paper
      aims to briefly review the anatomy, classification, mechanisms of injury, and
      diagnosis of SLAP lesions. Additionally, we will describe our treatment protocol
      for Type II SLAP lesions based on three groups of patients: throwing athletes,
      non-throwing athletes, and all other Type II SLAP lesions. Conclusion: The
      management of SLAP lesions can be divided into 4 broad categories: (1)
      nonoperative management that includes scapular exercise, restoration of balanced
      musculature, and that would be expected to provide symptom relief in 2/3 of all
      patients; (2) patients with a clear traumatic episode and symptoms of instability
      that should undergo SLAP repair without (age < 40) or with (age > 40) biceps
      tenotomy or tenodesis; (3) patients with etiology of overuse without instability
      symptoms should be managed by biceps tenotomy or tenodesis; and (4) throwing
      athletes that should be in their own category and preferentially managed with
      rigorous physical therapy centered on hip, core, and scapular exercise in
      addition to restoration of shoulder motion and rotator cuff balance. Peel-back
      SLAP repair, Posterior Inferior Glenohumeral Ligament (PIGHL) release, and
      treatment of the partial infraspinatus tear with debridement, PRP, or (rarely)
      repair should be reserved for those who fail this rehabilitation program.

PMID- 30197717
TI  - Fabella Syndrome Following De-Rotation Surgery to Correct a Femoral Malunion.
AB  - Background: The fabella is a sesamoid bone situated within the lateral head of
      the gastrocnemius tendon, close to the lateral femoral condyle, and adjoined to
      the fabellofibular ligament. It is a normal variant, found in up to 87% of
      patients. Fabella Syndrome describes traditionally posterolateral knee pain,
      occurring due to biomechanical pressure of the fabella against the lateral
      femoral condyle. Given its rarity, its diagnosis is often overlooked. We present
      a case of Fabella Syndrome with a modified surgical excision technique and review
      of the literature. Methods and Results: A thirty-four-year-old man presented with
      posterolateral knee pain following de-rotation surgery to correct a femoral
      malunion, from a previous femoral shaft fracture. Due to the patient's complex
      orthopaedic history, Fabella Syndrome was not initially diagnosed. Fabellectomy
      eliminated all symptoms of knee pain, with no limitations in knee function.
      Conclusion: Review of the literature identified ten publications (evidence level
      IV) describing Fabella Syndrome. This is the first reported case of Fabella
      Syndrome secondary to femoral de-rotation surgery. The authors recommend
      fabellectomy as a definitive treatment for Fabella Syndrome, in keeping with
      published literature.

PMID- 30197718
TI  - Simultaneous Accelerated Corneal Crosslinking and Laser In situ Keratomileusis
      for the Treatment of High Myopia in Asian Eyes.

PMID- 30197719
TI  - A New User-Friendly and Affordable Method in Descemet Stripping Endothelial
      Keratoplasty.
AB  - Aims: To describe a new technique in Descemet Stripping Automated Endothelial
      Keratoplasty (DSAEK). Materials and Methods: In this technique, we use easily
      available materials (mainly a Nelaton tube) to make an injector for loading DSAEK
      lenticule and also easily pulling it (using a gauge 23 needle) into the eye. In
      this paper, we report outcomes of this technique in four cases. Results: Using
      these available instruments could easily lead to a clear postoperative cornea.
      Mean Endothelial Cell Density (ECD) loss at sixth postoperative month was 26%.
      Conclusion: We proposed a novel effective user-friendly and affordable technique
      to perform DSAEK.

PMID- 30197720
TI  - Effects of a Mobile Educational Program for Colorectal Cancer Patients Undergoing
      the Enhanced Recovery After Surgery.
AB  - Background: The Enhanced Recovery After Surgery (ERAS) program hastens recovery
      from colorectal cancer by shortening the treatment period and enabling a return
      to normal activities. However, patients with colorectal cancer treated under the
      ERAS program have fewer opportunities to consult with medical staff and receive
      education regarding self-care and experience more affective stress and anxiety.
      Objective: This study aimed to develop and assess an educational program for
      patients with colorectal cancer treated under the ERAS program, considering
      affective aspects. Method: Patients with colorectal cancer (n = 118) who
      underwent open colon surgery under the ERAS program were assigned alternately in
      the order of admission on a 1:1 basis to a treatment group (n = 59) and
      conventional care group (n = 59). The treatment group received a two-week mobile
      based intervention, whereas the control group received conventional care. Quality
      of life, self-efficacy, anxiety, and depression were compared between the two
      groups. Results: The mobile web-based educational program significantly reduced
      the negative impact of surgery on the quality of life in the treatment group,
      compared with the conventional care group, and triggered a noticeable decline in
      anxiety and depression and increase in self-efficacy. Conclusion: The developed
      mobile web-based educational program effectively enhanced self-efficacy,
      positively impacted the quality of life, and reduced anxiety and depression. The
      program could have a positive effect on the quality of life of patients with
      colorectal cancer treated under the ERAS program.

PMID- 30197721
TI  - The Effect of Deworming School Children on Anemia Prevalence: A Systematic Review
      and Meta-Analysis.
AB  - Introduction: High prevalence of anemia attributable to intestinal parasite
      infection occurs among children in developing countries. As a result mass
      treatment of all children with anti-helminthic drugs particularly in school
      setting is being implemented. There are few studies conducted to assess impact of
      deworming on anemia prevalence among school children with inconclusive finding.
      Therefore we aimed to conduct a systematic review on impact assessment of
      deworming on anemia prevalence or hemoglobin level of school children so that
      policy makers and other stalk holders could have pooled evidence on the direction
      to make decision. Methods: The review was conducted through a systematic
      literature search of articles published between 1998 and 2015. Five bibliographic
      databases and libraries: PubMed/Medline, Global Health Database, Embase, the
      Cochrane Library, and African Index Medicus were used. After cleaning and
      sorting, analysis was performed using STATA version 11. The pooled estimate was
      through a fixed-effects model. Heterogeneity was assessed by the I2 and
      publication bias through funnel plot. Results: Eight studies were retained for
      final analysis which enrolled a total of 1,005,239 school children. The overall
      change in the hemoglobin level after deworming was 1.62(95%CI=1.01-2.25)
      gram/deciliter. There was no difference between the random effect model and the
      fixed effect model. The prevalence of anemia was markedly changed after the
      program, particularly in the studies which implemented deworming with hygiene
      program, co-administration of iron and retinol. Conclusion and Recommendation:
      School based deworming program decreases prevalence of anemia and will contribute
      to reduction of anemia in the community. Therefore the program should be expanded
      in all areas and integrated with other child care programs.

PMID- 30197722
TI  - Child-rearing Support Provided by Public Health Nurses to People with Mental
      Illness: Qualitative Descriptive Study.
AB  - Background: The growing rates of deinstitutionalization in Japan have resulted in
      an increase in the number of children being raised by parents with mental
      illness. Given this situation, public health nurses working for local governments
      play an important role. Objective: The purpose of this qualitative descriptive
      study was to describe the child-rearing support provided by public health nurses
      to parents with mental illness. Methods: Seven nurses identified 28 cases of
      parents with mental illness. Descriptions of the goals and details of the
      appropriate nursing support were extracted from transcripts, coded, and
      categorized. Results: Parents with mental illness diagnosed with addiction and
      personality disorders were more difficult to support than those diagnosed with
      mood disorders or schizophrenia. Public health nurses supported parents with
      mental illness with the aim of achieving goals such as "building continuous
      consultative relationships," "ensuring living conditions had a minimum level of
      safety and comfort," "parents playing their roles," "parents and children living
      together in the community," and "fostering children's growth." While they
      provided support by "assessing their relationships with parents," "building
      consultative relationships with parents," "assessing parents' illnesses/disorders
      and supporting," "assessing child-rearing abilities and supporting," and
      "cooperating with related agencies," they tended to focus on the growth of the
      children rather than the recovery of parents. Conclusion: Consultative
      relationships were the beginning of support, as well as the most important and
      difficult skill. Public health nurses need to provide support for the recovery of
      parents with mental illness and learn about personality disorders and addiction.

PMID- 30197723
TI  - HIV Prevention in Adolescents and Young People in the Eastern and Southern
      African Region: A Review of Key Challenges Impeding Actions for an Effective
      Response.

PMID- 30197724
TI  - Incident Angle Dependence of CHD3 Dissociation on the Stepped Pt(211) Surface.
AB  - The dissociation of methane on transition metal surfaces is not only of
      fundamental interest but also of industrial importance as it represents a rate
      controlling step in the steam-reforming reaction used commercially to produce
      hydrogen. Recently, a specific reaction parameter functional (SRP32-vdW) has been
      developed, which describes the dissociative chemisorption of CHD3 at normal
      incidence on Ni(111), Pt(111), and Pt(211) within chemical accuracy (4.2 kJ/mol).
      Here, we further test the validity of this functional by comparing the initial
      sticking coefficients (S0), obtained from ab-initio molecular dynamics
      calculations run using this functional, with those measured with the King and
      Wells method at different angles of incidence for CHD3 dissociation on Pt(211).
      The two sets of data are in good agreement, demonstrating that the SRP32-vdW
      functional also accurately describes CHD3 dissociation at off-normal angles of
      incidence. When the direction of incidence is perpendicular to the step edges, an
      asymmetry is seen in the reactivity with respect to the surface normal, with S0
      being higher when the molecule is directed toward the (100) step rather than the
      (111) terrace. Although there is a small shadowing effect, the trends in S0 can
      be attributed to different activation barriers for different surface sites, which
      in turn is related to the generalized co-ordination numbers of the surface atom
      to which the dissociating molecule is adsorbed in the transition state.
      Consequently, most reactivity is seen on the least co-ordinated step atoms at all
      angles of incidence.

PMID- 30197725
TI  - Oriented Attachment and Nanorod Formation in Atomic Layer Deposition of TiO2 on
      Graphene Nanoplatelets.
AB  - Understanding the spontaneous organization of atoms on well-defined surfaces
      promises to enable control over the shape and size of supported nanostructures.
      Atomic layer deposition (ALD) boasts atomic-scale control in the synthesis of
      thin films and nanoparticles. Yet, the possibility to control the shape of ALD
      grown nanostructures remains mostly unexplored. Here, we report on the bottom-up
      formation of both linear and V-shaped anatase TiO2 nanorods (NRs) on graphene
      nanoplatelets during TiCl4/H2O ALD carried out at 300  degrees C. NRs as large as
      200 nm form after only five ALD cycles, indicating that diffusional processes
      rather than layer-by-layer growth are behind the NR formation. In particular,
      high-resolution transmission electron microscopy reveals that the TiO2 NRs and
      graphene nanoplatelets are in rotational alignment as a result of lattice
      matching. Crucially, we also show that individual nanocrystals can undergo in
      plane oriented attachment.

PMID- 30197726
TI  - Using Scaffolding and Deliberate Practice to Improve Abstract Writing in an
      Introductory Biology Laboratory Course.
AB  - s play the pivotal role of selling an article to a prospective reader, and for
      students, the ability to communicate science in concise written form may foster
      scientific thinking. However, students struggle with abstract composition, and we
      lack evidence-based educational innovations to help them develop this skill. We
      designed, implemented, and assessed an intervention for abstract composition with
      elements of scaffolding and transparency to ask whether deliberate practice
      improves concise scientific writing in early career undergraduate biology majors.
      We evaluated student performance by analyzing abstracts written before and after
      the intervention and by assessing pre- and posttest student concept maps. We
      found that scaffolded learning improved student abstract writing, with the
      greatest gains in students' ability to describe the motivation for their work.
      Using a set of tested tools to teach scientific writing has important
      implications for strengthening students' capacity to reinforce and synthesize
      content in the future, whether that is in laboratory course exercises, in
      independent research, or as a transferable skill to general critical thinking.

PMID- 30197727
TI  - Exploring Infectious Disease Outbreaks and Herd Immunity Through Simulations with
      a Visual Appeal.

PMID- 30197728
TI  - Role-Playing Activity to Demonstrate Diffusion Across a Cell Membrane.

PMID- 30197729
TI  - The Use of Baker's Yeast in the Resazurin Reduction Test: A Simple, Low-Cost
      Method for Determining Cell Viability in Proliferation and Cytotoxicity Assays.

PMID- 30197730
TI  - Developing Course-Based Research Experiences in Discipline-Based Education
      Research: Lessons Learned and Recommendations.
AB  - In this perspective, we highlight the opportunity for the biology education
      research community to develop course-based research experiences (CREs) or course
      based undergraduate research experiences (CUREs) in discipline-based education
      research. Building on our prior experience developing and teaching four biology
      education research CREs, we present opportunities, potential pitfalls, and
      recommendations for discipline-based education researchers interested in
      integrating their research and teaching in the context of a CRE.

PMID- 30197731
TI  - It Takes a Village: Workflow to Publish a Peer-Reviewed Article.

PMID- 30197732
TI  - A Simple Exercise for Teaching Bacteriophage Concepts in the Undergraduate
      Laboratory Using Commercially Available Disinfectant.

PMID- 30197733
TI  - Tuberculosis infection among health care workers: a case series in two district
      hospitals, Kenya, August 2013.
AB  - Introduction: health care workers (HCWs) have an increased risk of M.
      tuberculosis infection and tuberculosis (TB) disease compared to the general
      population. We evaluated the magnitude of TB disease among HCWs in two District
      Hospitals in Kenya. Methods: retrospective review of TB laboratory registers was
      performed at Makindu and Kiambu district hospitals. Cases were HCWs with
      confirmed TB diagnosis working at either hospital from 2010 to 2013. Cases were
      interviewed using structured questionnaire to collect clinical and epidemiologic
      information. Infection prevention (IP) practices were observed and recorded.
      Results: Makindu and Kiambu had 91 and 450 HCWs respectively. As from the
      registers, 6,275 sputum smears were examined with 1,122 (18%) acid alcohol fast
      bacilli smear positive. Kiambu and Makindu reported 11 and five cases of TB among
      HCWs respectively. Of the 16, 57% were male; mean age was 45 (SD 5.32) years.
      HCWs affected were: four (25%) laboratory technicians, four (25%) nurses, two
      (13%) occupation therapists, two (13%) clinical officers and one pharmacist,
      telephone operator, driver and casual worker. Mean working time lost recuperating
      was 14 (range: 0-28) weeks. Both facilities lacked high-efficiency particulate
      air filters and Kiambu hospital lacked a biosafety cabinet too. Windows at both
      facilities were often closed and suspected TB patients shared common crowded
      outpatient waiting area where sputum was also collected. No standard reporting
      tool for TB disease among HCWs was in place at both facilities. Conclusion: TB
      disease was distributed across professional cadres with long working time lost
      recuperating. Inadequate IP measures exposed HCWs to occupational risk of
      acquiring TB disease.

PMID- 30197734
TI  - Antimicrobial residues and compositional quality of informally marketed raw cow
      milk, Lamu West Sub-County, Kenya, 2015.
AB  - Introduction: unadulterated milk, free of antimicrobial residues is important for
      industrial processing and consumers' health. Antimicrobial residues in foods of
      animal origin can cause adverse public health effects like drug resistance and
      hypersensitivity. Milk produced in Lamu West sub-county is sold raw directly to
      consumers. We estimated the compositional quality and prevalence of antimicrobial
      residues in informally marketed raw cow milk in Lamu West Sub-County, Kenya.
      Methods: we randomly recruited 152 vendors and 207 farmers from four randomly
      selected urban centers in a cross-sectional study and interviewed them using a
      pretested standardized questionnaire. A100-ml raw milk sample was aseptically
      collected from each vendor and farm and tested for antimicrobial residues using
      Charm Blue Yellow II kit following the European Union Maximum Residue Limits (EU
      MRLs) while an Ekomilk(r) Analyzer was used to measure compositional quality
      where samples with either solid not fat (SNF) < 8.5 or added water >= 0.01% or
      both were considered adulterated. We analyzed data using univariate analysis and
      unconditional logistic regression to calculate odds ratios (OR) and 95%
      confidence intervals (CI). Results: thirty-two of the 207 (15.5%) samples from
      farmers and 28 (18.4%) of the 152 samples from vendors tested positive for
      antimicrobial residues. Thirty-six (17.4 %) samples from farmers and 38 (25.0%)
      from vendors were found to be adulterated with water. Farmers' awareness of the
      danger of consuming milk with antimicrobial residues and farmers having training
      on good milking practices were protective against selling milk with antimicrobial
      residues (adjusted OR and 95% CI 0.20, 0.07-0.55 and 0.33, 0.11-0.99,
      respectively). Conclusion: the antimicrobial residues above EU MRLs and
      adulteration of raw marketed cow milk observed in this study provide evidence for
      routine testing of marketed milk and educating farmers to observe antimicrobial
      withdrawal period.

PMID- 30197735
TI  - Folate deficiency and utilization of folic acid fortified flour among pregnant
      women attending antenatal clinic at Pumwani Maternity Hospital, Kenya, 2015.
AB  - Introduction: in 2012, the Government of Kenya amended the Food, Drug and
      Chemical Substances Act to make the fortification of maize and wheat flour with
      folic acid mandatory. We assessed folate deficiency, awareness and use of folic
      acid fortified flour among pregnant women receiving antenatal care (ANC) at a
      clinic at Pumwani Maternity Hospital, Kenya, 2015. Methods: we conducted a cross
      sectional survey at Pumwani Maternity Hospital between October and November 2014.
      We enrolled pregnant women who received ANC and interviewed them using a semi
      structured questionnaire after obtaining informed consent. Blood samples were
      collected from all study participants and serum folate level was analyzed by
      electrochemiluminescence immunoassay. Folate deficiency was defined as serum
      folate of < 10nmols/L and borderline folate deficiency was defined as serum
      folate of between 10nmols/L and 15nmols/L. Results: among the 247 study
      participants, two (1%) had folate deficiency. One hundred and seventy-nine
      (73.4%) had heard about folic acid, but only 56 (23%) had heard about folic acid
      fortified flour. Overall, 198 (80%) study participants consumed fortified brands
      of maize flour and 205 (84%) consumed fortified brands of wheat flour; only four
      (2%) and two (1%) of study participants consumed specific brands of maize and
      wheat flour respectively because they were fortified. Conclusion: the prevalence
      of folate deficiency was low and this may have been because of the availability
      of fortification programs. Although there was limited knowledge of fortified
      flour, utilization was high. The Kenyan Ministry of Health should enforce
      implementation of the legislation on maize flour and wheat flour fortification by
      all milling industries.

PMID- 30197736
TI  - [Complex management of macrodactylia of the hand: between aesthetic and
      functional prejudice].
AB  - Macrodactylia is a rare congenital malformation of unknown origin that can affect
      the fingers or the toes. It is characterized by an increase in the size of all
      the elements of one or more rays, recognizable at birth or occurring in a
      progressive manner. Social, aesthetic as well as functional impact imposes early
      surgical management or even amputations in advanced forms. We report the case of
      a 18-year old unmarried, left handed patient without a profession, admitted to
      the Department of Burns, Plastic and Aesthetic Surgery at the University Hospital
      Mohammed VI in Marrakech, with progressive acrodactylia involving the first and
      the second ray of the right hand. Clinical examination showed hypertrophy of the
      first two rays of the right hand associated with predominant fibro-fatty
      infiltration of the palmar as well as phalanx deviation 90 degrees at the level
      of the second finger. Given the severity of the macrodactylia, amputation of the
      second ray associated with reduction of the fatty infiltration of the palmar was
      proposed to the patient, allowing him to maintain pollici-digital pinch and to
      return to a social life as close as possible to normal life.

PMID- 30197737
TI  - [Black henna tattoo: risk of developing allergic contact eczema].
AB  - Henna is used for coloring hair, but also to draw labile skin tattoo. Henna is
      often mixed with paraphenylenediamine (PPD). We report the case of a female
      patient presenting with contact eczema due to labile tattoo containing PPD. The
      study involved a 23-year old young woman with an aesthetic Black Henna tattoo on
      the back of the hand and on the forearm. This labile tattoo contained PPD. Two
      days later, the patient developed intensely pruritic, burning
      erythematovesiculosus and edematous lesions. The lesions involved the tattooed
      area, corresponding with the original drawing. The lesions were improved using
      Class 1 of topical corticosteroids (Clobetasol propionate). The patient refused
      allergy patch testing, so no allergy test was performed. Now, henna is very
      popular in the western countries. PPD is added to reduce the fixing time or to
      obtain a darker coloration. It can result in severe systemic reactions. The most
      frequent allergic reaction is contact dermatitis. Treatment is based on local
      corticosteroid therapy. A better regulation on labile tattoo, the control of
      preparations as well as a regular annual information for the general public are
      essential. The interest of our study lies in highlighting the importance of
      informing, especially young people, on the risks of labile tattoo.

PMID- 30197738
TI  - [Recurrence of capsular pseudoexfoliation on intraocular implant].
AB  - We here report the case of a 79-year old patient who underwent cataract by
      phacoemulsification associated with preoperative left and right eyes pseudo
      capsular exfoliation in 2000. He had pseudo-exfoliative glaucoma with recurrence
      on the implant.

PMID- 30197739
TI  - [Intraperitoneal cystic lymphangioma and Crohn's disease: an exceptional
      association].
AB  - Cystic lymphangioma is a rare benign malformative tumor of the lymphatic vessels
      which may occur in various locations. Intra-abdominal cystic lymphangioma is less
      frequent than cervicoaxillary cystic lymphangioma. Clinical presentation is
      polymorphic. Diagnosis is based on imaging data but it requires histological
      confirmation. Surgery is the gold standard treatment. We here report a rare case
      of acquired intraperitoneal cystic lymphangioma secondary to subtotal colectomy
      in a female patient with severe evolutive Crohn's disease treated with anti-TNF
      alpha. The patient presented with irreducible right painful paramedian mass with
      no impulse on coughing, suggesting the diagnosis of strangulated eventration
      within a surgical scar from midline laparotomy. She underwent emergency surgery.
      Surgical exploration showed multi-cystic intraperitoneal mass protrunding through
      the right paramedian eventration. Anatomo-pathological examination helped to
      confirm the diagnosis of cystic lymphangioma. Postoperatively, the mass was
      punctured twice to evacuate the fluid, because of incomplete surgical resection.
      This is the first reported case of cystic lymphangioma in a patient under anti
      TNF alpha. It could be caused by disruption of the immune system and more
      specifically of the lymphocyte population. This association has not hitherto been
      established and experimental studies are necessary to accept or refuse this
      hypothesis.

PMID- 30197740
TI  - Physiological and psychosocial stressors among hemodialysis patients in the Buea
      Regional Hospital, Cameroon.
AB  - Introduction: End Stage Renal Disease (ESRD) is an irreversible kidney condition
      and hemodialysis is the most frequent treatment option used for this condition.
      However, hemodialysis also has a detrimental impact on the quality of life and
      the individuals' physical and psychosocial wellbeing. The main objective of this
      study was to identify physiological and psychosocial stressors faced by patients
      undergoing hemodialysis in the Buea Regional Hospital in Cameroon. Methods: A
      cross-sectional study was carried out (December 2016 - January 2017) among
      patients undergoing hemodialysis at the Buea regional hospital. Data were
      collected with the use of a structured questionnaire and analyzed using SPSS
      version 21.0. Quantitative variables were expressed as frequencies, percentages
      and means. Results: Among the patients undergoing hemodialysis, 28 (70.0%) were
      below 5-year dialysis while 12 (30.0%) had been on dialysis for five years and
      more. 21(52.5%) were male and 19(47.5%) female. Half of the patients were married
      20(50%), 13(32.5%) were single, 6(15%) were divorced, and one (2.5%) was a
      widower. Also, 28 (70.0%) were below 5-year dialysis while 12 (30.0%) had been on
      dialysis for five years and more. All participants experienced at least one or
      more physiological and psychosocial stressors. Among physiological stressors, the
      most frequent were feeling tired (97%), followed by arterial and venous stick
      (88%) while itching (49.5%) was the least noted physiological stressor. Among
      psycho-social stressors, the most recurrent were transportation to and from the
      hospital (99.5%), cost of treatment (99.5%) and Limits on time and place of
      vacation (99%), followed by Limitation in physical activities, frequent
      hospitalizations, the length of time on dialysis, uncertainty about the future,
      changes in life style, increased dependence and sleep disturbances. Conclusion:
      The topic of stressors is of importance among patients receiving dialysis, as
      these affect their psycho-social and physiological wellbeing. Thus,
      nephrologists, nurses and family members play an important role in providing
      patients with effective psycho-social and physiological support.

PMID- 30197741
TI  - Status of Ebola Virus Disease (EVD) preventive practices among Health care
      workers (HCWs) in Benin City: a year after disease containment in Nigeria.
AB  - Introduction: Ebola Virus Disease (EVD) is of great public health importance.
      Health care workers (HCWs) in various health care facilities especially in
      developing countries such as Nigeria, are particularly vulnerable to the disease.
      It is therefore imperative that health care workers adopt the necessary
      preventive practices to reduce to the barest minimum the risk of infection
      transmission. The study assessed the factors associated with EVD preventive
      practices among HCWs in a tertiary institution in Benin City, Nigeria. Methods: A
      total of 374 health care workers selected using a two-staged sampling technique
      participated in this descriptive cross-sectional study. Data were collected using
      structured, self-administered questionnaires and analyzed with IBM SPSS, version
      21.0. Univariate and bivariate analysis were done. Level of significance was set
      at p < 0.05. Results: The mean age of respondents was 36.3 +/- 8.0 years. All,
      374 (100.0%) of the respondents were aware of EVD and 347 (92.8%) of respondents
      had good knowledge of EVD. More than half of the respondents, 228 (61.0%) and 201
      (53.7%) had positive attitude towards EVD and good EVD preventive practices
      respectively. A higher proportion of respondents with positive attitude towards
      EVD were observed to have good preventive practice (p < 0.05). Conclusion:
      Knowledge, attitude and preventive practices towards EVD among HCWs were
      generally good. Positive attitude towards EVD was significantly associated with
      good preventive practices.

PMID- 30197742
TI  - Reasons for low level of skilled birth attendance in Afar pastoralist community,
      North East Ethiopia: a qualitative exploration.
AB  - Introduction: Ethiopia has expanded the number of health facilities that offer
      maternal health services during the last two decades. However, the utilization of
      skilled birth attendants in health facilities is still very low especially among
      the pastoralist regions of the country. This study explored why women in the
      pastoralist region of Afar, Ethiopia still prefer to give birth at home. Methods:
      A qualitative study approach was used to collect information from October to
      December 2015. A total of eighteen focus group discussions and twenty-four key
      informant interviews were conducted. Focus group discussions were separately
      conducted with mothers and male tribal or religious leaders. Key informant
      interviews were conducted with heads of Women's Affairs Bureau, district health
      office heads and traditional birth attendants. Data were coded and categorized
      using open code software for qualitative data management and analyzed based on a
      thematic approach. Results: Women preferred to deliver at home due to lack of
      awareness about the benefits of maternity health facilities, their nomadic
      lifestyle, lack of confidence and trust in health workers and their close
      affinity and easy access to traditional birth attendants. Supply-side barriers
      included distant health facilities, lack of transportation and poor health care.
      Conclusion: Demand and supply related factors were identified as barriers to
      utilization of skilled birth attendants. Increasing awareness, bringing the
      service closer, arranging maternity waiting area around health facilities, and
      creating client-friendly service were found critical. Future research to define
      and improve services and approaches suitable for pastoralist population is
      warranted.

PMID- 30197743
TI  - Solitary epidural lipoma.

PMID- 30197744
TI  - Metastasis of renal cell carcinoma to the pancreas 11 years postnephrectomy.

PMID- 30197745
TI  - [Case of thyroid ectopia in the hyoid region in a young Malagasy girl].
AB  - Thyroid ectopia is rare. It results from a failure of migration of the thyroid
      gland during its embryonic development. It is most often asymptomatic. We here
      report a case of thyroid ectopia in the hyoid region in a young Malagasy girl,
      presenting as aesthetic discomfort associated with subclinical hypothyroidism.
      Diagnosis was confirmed using cervical ultrasound and scintigraphy with
      technetium-99m. Hormone replacement therapy is the gold standard even in patients
      with subclinical hypothyroidism because it results in physiologic euthyroidism
      and good clinical evolution.

PMID- 30197746
TI  - Erratum: Food hygiene assessment in catering establishments in Hay Hassani
      district-Casablanca.
AB  - [This corrects the article DOI: 10.11604/pamj.2016.24.335.9171.].

PMID- 30197747
TI  - Knowledge of Lassa fever and use of infection prevention and control facilities
      among health care workers during Lassa fever outbreak in Ondo State, Nigeria.
AB  - Introduction: Hospital-acquired infections of Lassa fever (LF) have been
      described in many West African countries. We assessed the availability of
      Infection Prevention and Control (IPC) measures and their use in the health
      centres (HCs) at the affected Local Government Areas (LGAs) during an ongoing LF
      outbreak in Ondo State, Nigeria. Methods: We included all primary and secondary
      HCs and their healthcare workers (HCWs) in the affected Ose and Owo LGAs. We
      collected data from respondents using self-administered questionnaires and used a
      checklist to assess the IPC measures at the HCs. We generated frequencies and
      proportions and tested associations using odds ratios at 95% CI. Results: One
      hundred and ninety HCWs from 59 HCs were surveyed of which 34 (57.6%) were
      located in Owo LGA. All HCs had soap for handwashing, 57(96.6%) had wash-hand
      basins but only 52(88.1%) had water. While 57(96.6%) had gloves and 53(89.8%) had
      sharps boxes, only 16(27.1%) had an isolation room. Only 44(23.2%) respondents
      had been trained in IPC. The majority, 144 (91.6%) always had gloves available
      for their use, 79(41.6%) always had facemask/shield and 71(37.4%) always had full
      personal protective equipment. At the last patient contact, only 151 (79.8%)
      washed their hands before the contact, 188(98.9%) washed their hands after and
      183 (96.2%) wore gloves. While there was no association between availability of
      gloves and its use (OR: 0.21, 95%CI 0.04-1.17), there was significant association
      between having had training in basic universal precautions and having used gloves
      (OR: 3.64, 95%CI 1.21-19.40) and having washed hands after last patient contact
      (OR: 2.31, 95%CI 1.67-12.30). Conclusion: Among these HCs that serve as point of
      first contact with possible cases of LF in these endemic LGAs, none met the
      minimum standard for IPC. We recommend that IPC committee for each LGA and the
      whole state should be set up and IPC trainings made mandatory.

PMID- 30197748
TI  - [Advanced lymphomatous tumor of the trunk].
AB  - Malignant lymphomas are a group of cancers that arise in the lymphoid tissue, in
      the lymph nodes or in extranodal sites due to neoplastic lymphocytic cell
      transformation. Within this group, malignant non-Hodgkin lymphomas are
      distinctive. We report a case of diffuse advanced and extremely aggressive
      malignant cutaneous non-Hodgkin lymphoma. The study involved a 30-year old
      patient, driver, married and father of one child, followed-up in the Department
      of Hematology and Oncology for 2 years due to malignant non-Hodgkin lymphoma
      diagnosed on the basis of axillary and inguinal polyadenopathies. The patient
      underwent 13 chemotherapy sessions. He was admitted to the Department of Plastic,
      Cosmetic and Burn Surgery at the University Hospital Mohammed VI in Marrakech
      with skin involvement of his lymphoma manifesting as an advanced left latero
      thoracic tumor rapidly increasing in size. On clinical examination, his general
      condition was quite good. It showed voluminous left latero-thoracic mass adherent
      to its deeper structure with ipsilateral axillary shield. Partial biopsy was
      performed. Anatomo-pathological examination confirmed the diagnosis of diffuse
      malignant large B-cells non-Hodgkin's lymphoma. Immunohistochemical and genetic
      study was not performed. Serology tests were negative. Serial Computed Tomography
      (CT) scan showed voluminous left antero-lateral predominantly axillary and
      thoracic ganglionic mass made of confluent lymph nodes, with persistence of
      peripheral lymph nodes, skin ulcers and necrotic areas measuring 30cm in
      diameter. In our Hospital, the patient underwent wide tumor resection, then
      coverage with a split-thickness skin, thus reducing tumor volume and ensuring
      better patient's comfort. When the patient started healing, he was referred to
      the Department of Hematology and Oncology for complementary treatment.

PMID- 30197749
TI  - Verbal Aggression in Animated Cartoons.
AB  - Relying upon a content analysis of one specific type of medium to which young
      people are exposed beginning at an early age, on a regular basis, and for many
      years (i.e., animated cartoons), the present study examines what types of
      messages are provided about verbal aggression. This research examines the
      following issues: (1) How prevalent is verbal aggression in animated cartoons?
      (2) Has this prevalence changed over time? (3) What characteristics tend to be
      associated with being a perpetrator of verbal aggression? (4) What reasons are
      given for why cartoon characters engage in verbal aggression? (6) What "types" of
      characters are yelled at, threatened, insulted, and so forth? Results indicate
      that verbal aggression is fairly prevalent in cartoons (it is the second most
      common type of antisocial behavior shown, ranking second only to violence) and
      that this prevalence has increased greatly over time. Cartoons tend to normalize
      verbal aggression, both by virtue of its frequency of occurrence and by the lack
      of patterning of characteristics associated with perpetrating this behavior.
      Although many (nearly half) of the reasons implied for being verbally aggressive
      are negative in nature, a substantial proportion of the time, this behavior is
      undertaken for positive reasons or for no reason at all. Characters of all types
      are equally likely to be verbally aggressive for negative reasons, although only
      certain types of characters (e.g., female, intelligent, "good guys," physically
      attractive) are shown to engage in this behavior for positive reasons.

PMID- 30197750
TI  - Distinguishing mechanisms of adverse drug reactions from mechanisms of actions of
      drugs.

PMID- 30197751
TI  - Clinical utility of chromatin analysis.

PMID- 30197752
TI  - An intestinal stem cell niche in Apc mutated neoplasia targetable by CtBP
      inhibition.
AB  - C-terminal binding protein 2 (CtBP2) drives intestinal polyposis in the Apcmin
      mouse model of human Familial Adenomatous Polyposis. As CtBP2 is targetable by an
      inhibitor of its dehydrogenase domain, understanding CtBP2's role in adenoma
      formation is necessary to optimize CtBP-targeted therapies in Apc mutated human
      neoplasia. Tumor initiating cell (TIC) populations were substantially decreased
      in ApcminCtbp2+/- intestinal epithelia. Moreover, normally nuclear Ctbp2 was
      mislocalized to the cytoplasm of intestinal crypt stem cells in Ctbp2+/- mice,
      both Apcmin and wildtype, correlating with low/absent CD133 expression in those
      cells, and possibly explaining the lower burden of polyps in Apcmin Ctbp2+/-
      mice. The CtBP inhibitor 4-chloro-hydroxyimino phenylpyruvate (4-Cl-HIPP) also
      robustly downregulated TIC populations and significantly decreased intestinal
      polyposis in Apcmin mice. We have therefore demonstrated a critical link between
      polyposis, intestinal TIC's and Ctbp2 gene dosage or activity, supporting
      continued efforts targeting CtBP in the treatment or prevention of Apc mutated
      neoplasia.

PMID- 30197753
TI  - A novel molecular mechanism for a long non-coding RNA PCAT92 implicated in
      prostate cancer.
AB  - The role of many lncRNAs in cancer remains elusive including that for a Prostate
      Cancer Associated Transcript 92 (PCAT92). PCAT92 shares the locus on chromosome
      13 with ABCC4 gene, known to be implicated in prostate cancer. It has been shown
      that PCAT92 and ABCC4 are up-regulated in prostate cancer samples from multiple
      transcriptome datasets. Among the prostate cancer cell-lines LNCaP showed maximum
      overexpression of PCAT92 compared to control cell-line RWPE-1. We have shown that
      knockdown of PCAT92 in LNCaP cells reduces cell viability and proliferation and
      down-regulates ABCC4 transcript/protein expression. The shared region between
      PCAT92 and ABCC4 has a binding site for an oncogenic transcription factor (ZIC2)
      which is also upregulated in the majority of datasets studied here. ZIC2 binding
      to the predicted ABCC4 promoter has been confirmed using pull-down assay.
      Interestingly, under PCAT92 knockdown condition, there is a reduction in the ZIC2
      binding to ABCC4 promoter indicating the potential involvement of PCAT92 in the
      recruitment of ZIC2. We have identified distinct regions on PCAT92 with potential
      to bind to ZIC2 non-DNA binding Zinc-finger domain and potential for triplex
      formation near ABCC4 promoter region, which have been experimentally validated.
      Together, these observations and localization in the nucleus suggests that PCAT92
      may play a role in prostate cancer by increasing the local concentration of ZIC2
      by forming RNA-DNA triplex near ABCC4 promoter thus helping in recruitment of
      ZIC2 for ABCC4 regulation.

PMID- 30197754
TI  - Integrin alpha2beta1 decelerates proliferation, but promotes survival and
      invasion of prostate cancer cells.
AB  - High expression level of integrin alpha2beta1 is a hallmark of prostate cancer
      stem cell like cells. The role of this collagen receptor is controversial since
      it is down regulated in poorly differentiated carcinomas, but concomitantly
      proposed to promote metastasis. Here, we show that docetaxel resistant DU145
      prostate cancer cells express high levels of alpha2beta1 and that alpha2beta1High
      subpopulation of DU145 cells proliferates slower than the cells representing
      alpha2beta1Low subpopulation. To further study this initial observation we used
      Crispr/Cas9 technology to create an alpha2beta1 negative DU145 cell line.
      Furthermore, we performed rescue experiment by transfecting alpha2 knockout cells
      with vector carrying alpha2 cDNA or with an empty vector for appropriate control.
      When these two cell lines were compared, alpha2beta1 positive cells proliferated
      slower, were more resistant to docetaxel and also migrated more effectively on
      collagen and invaded faster through matrigel or collagen. Integrin alpha2beta1
      was demonstrated to be a positive regulator of p38 MAPK phosphorylation and a
      selective p38 inhibitor (SB203580) promoted proliferation and inhibited invasion.
      Effects of alpha2beta1 integrin on the global gene expression pattern of DU145
      cells in spheroid cultures were studied by RNA sequencing. Integrin alpha2beta1
      was shown to regulate several cancer progression related genes, most notably
      matrix metalloproteinase-1 (MMP-1), a recognized invasion promoting protein. To
      conclude, the fact that alpha2beta1 decelerates cell proliferation may explain
      the dominance of alpha2beta1 negative/low cells in primary sites of poorly
      differentiated carcinomas, while the critical role of alpha2beta1 integrin in
      invasion stresses the importance of this adhesion receptor in cancer
      dissemination.

PMID- 30197755
TI  - "Two hits - one stone"; increased efficacy of cisplatin-based therapies by
      targeting PCNA's role in both DNA repair and cellular signaling.
AB  - Low response rate and rapid development of resistance against commonly used
      chemotherapeutic regimes demand new multi-targeting anti-cancer strategies. In
      this study, we target the stress-related roles of the scaffold protein PCNA with
      a cell-penetrating peptide containing the PCNA-interacting motif APIM. The APIM
      peptide increased the efficacy of cisplatin-based therapies in a muscle-invasive
      bladder cancer (MIBC) solid tumor model in rat and in bladder cancer (BC) cell
      lines. By combining multiple omics-levels, from gene expression to
      proteome/kinome and metabolome, we revealed a unique downregulation of the
      EGFR/ERBB2 and PI3K/Akt/mTOR pathways in the APIM-peptide-cisplatin combination
      treated cells. Additionally, the combination treatment reduced the expression of
      anti-apoptotic proteins and proteins involved in development of resistance to
      cisplatin. Concurrently, we observed increased levels of DNA breaks in
      combination treated cells, suggesting that the APIM-peptide impaired PCNA - DNA
      repair protein interactions and reduced the efficacy of repair. This was also
      seen in cisplatin-resistant cells, which notably was re-sensitized to cisplatin
      by the APIM-peptide. Our data indicate that the increased efficacy of cisplatin
      treatment is mediated both via downregulation of known oncogenic signaling
      pathways and inhibition of DNA repair/translesion synthesis (TLS), thus the APIM
      peptide hits both nuclear and cytosolic functions of PCNA. The novel multi
      targeting strategy of the APIM-peptide could potentially improve the efficacy of
      chemotherapeutic regiments for treatment of MIBC, and likely other solid tumors.

PMID- 30197756
TI  - SPIN1 is a proto-oncogene and SPIN3 is a tumor suppressor in human seminoma.
AB  - SPIN1 is necessary for normal meiotic progression in mammals. It is overexpressed
      in human ovarian cancers and some cancer cell lines. Here, we examined the
      functional significance and regulation of SPIN1 and SPIN3 in the TCam-2 human
      seminoma cell line. We found that while SPIN1 overexpression reduced apoptosis in
      these cells, SPIN3 overexpression induced it. Similarly, SPIN1 upregulated and
      SPIN3 downregulated CYCD1, which is a downstream target of the PI3K/AKT pathway
      and contributes to apoptosis resistance in cancer cell lines. It appears that
      SPIN1 is pro-oncogenic and SPIN3 acts as a tumor suppressor in TCam-2 cells. To
      our knowledge, this is the first report of SPIN3 tumor suppressor activity.
      However, both SPIN1 and SPIN3 stimulated cell cycle progression. In addition,
      using luciferase reporters carrying SPIN1 or SPIN3 mRNA 3'UTRs, we found that
      PUM1 and PUM2 targeted and repressed SPINs. We also found that PUM1 itself
      strongly stimulated apoptosis and moderately slowed cell cycle progression in
      TCam-2 cells, suggesting that PUM1, like SPIN3, is a tumor suppressor. Our
      findings suggest that acting, at least in part, through SPIN1 and SPIN3, PUM
      proteins contribute to a mechanism promoting normal human male germ cell
      apoptotic status and thus preventing cancer.

PMID- 30197757
TI  - Zac1 regulates IL-11 expression in osteoarthritis.
AB  - Interleukin (IL)-11, a member of the IL-6 family of cytokines, exerts pleiotropic
      effects under normal and various disease conditions. We assessed IL-11 expression
      regulation and the IL-11/IL-6 ratio in osteoarthritis (OA) to better guide
      clinical therapeutic decision-making. Our findings suggest that Zac1, a zinc
      finger protein that regulates apoptosis and cell cycle arrest, is a transcription
      factor regulating IL-11 expression. Zac1 overexpression or knockdown respectively
      induced or suppressed IL-11 expression in HeLa cells. Zac1 acted synergistically
      with AP-1, human papillomavirus E2, and hypoxia inducible factor 1 alpha
      (HIF1alpha). IL-11 expression under various conditions, including hypoxia or
      treatment with phorbol 12-myristate 13-acetate or copper sulfate. Recombinant IL
      11-induced phosphorylation of signal transducer and activator of transcription 3
      at tyrosine 705 was reduced in a dose-dependent manner in HeLa cells. Cross-talk
      between Zac1, IL-11, p53, and suppressor of cytokine signaling 3 was
      differentially affected by copper sulfate, digoxin, and caffeine. Finally,
      aggressive vs. conventional treatment of OA patients was primarily determined by
      IL-6 levels. However, we suggest that OA patients with higher IL-11 levels may
      respond well to conventional treatments, even in the presence of high IL-6.

PMID- 30197758
TI  - Therapeutic targeting of Aurora A kinase in Philadelphia chromosome-positive ABL
      tyrosine kinase inhibitor-resistant cells.
AB  - Abelson murine leukemia viral oncogene homolog (ABL) tyrosine kinase inhibitors
      (TKIs) have been shown to be effective for treatment of chronic myeloid leukemia
      (CML) and Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia
      patients. However, resistance to ABL TKIs can develop as a result of breakpoint
      cluster region-ABL point mutations. Aurora kinases regulate many processes
      associated with mitosis. In this study, we investigated whether inhibiting Aurora
      kinase can reduce the viability of Ph+ leukemia cells. Treatment with the Aurora
      kinase A inhibitor alisertib blocked Ph+ leukemia cell proliferation and Aurora
      kinase A phosphorylation; it also induced G2/M-phase arrest and increased the
      intracellular levels of reactive oxygen species. Combined treatment of Ph+ cells
      with ABL TKIs and alisertib was cytotoxic, with the fraction of senescent cells
      increasing in a time- and dose-dependent manner. Aurora A gene silencing
      suppressed cell proliferation and enhanced ABL TKI efficacy. In a mouse xenograft
      model, co-administration of ponatinib and alisertib enhanced survival and reduced
      tumor size; moreover, the treatments were well tolerated by the animals. These
      results indicate that inhibiting Aurora kinase can enhance the cytotoxic effects
      of ABL TKIs and is, therefore, an effective therapeutic strategy against ABL TKI
      resistant cells, including those with the T315I mutation.

PMID- 30197759
TI  - miR-193b and miR-30c-1* inhibit, whereas miR-576-5p enhances melanoma cell
      invasion in vitro.
AB  - In cancer cells, microRNAs (miRNAs) are often aberrantly expressed resulting in
      impaired mRNA translation. In this study we show that miR-193b and miR-30c-1*
      inhibit, whereas miR-576-5p accelerates invasion of various human melanoma cell
      lines. Using Boyden chamber invasion assays the effect of selected miRNAs on the
      invasive capacity of various human melanoma cell lines was analyzed. Upon gene
      expression profiling performed on transfected A375 cells, CTGF, THBS1, STMN1,
      BCL9, RAC1 and MCL1 were identified as potential targets. For target validation,
      qPCR, Western blot analyses or luciferase reporter assays were applied. This
      study reveals opposed effects of miR-193b / miR-30c-1* and miR-576-5p,
      respectively, on melanoma cell invasion and on expression of BCL9 and MCL1,
      possibly accounting for the contrasting invasive phenotypes observed in A375
      cells transfected with these miRNAs. The miRNAs studied and their targets
      identified fit well into a model proposed by us explaining the regulation of
      invasion associated genes and the observed opposed phenotypes as a result of
      networked direct and indirect miRNA / target interactions. The results of this
      study suggest miR-193b and miR-30c-1* as tumor-suppressive miRNAs, whereas miR
      576-5p appears as potential tumor-promoting oncomiR. Thus, miR-193b and miR-30c
      1* mimics as well as antagomiRs directed against miR-576-5p might become useful
      tools in future therapy approaches against advanced melanoma.

PMID- 30197760
TI  - Genomic mutations and histopathologic biomarkers in Y90 radioembolization for
      chemorefractory colorectal liver metastases.
AB  - Background: To investigate mutational load and histologic biomarkers as
      prognostic factors in patients with chemorefractory colorectal liver metastases
      (CRLM) treated with Y-90 radioembolization therapy. Materials and Methods: Single
      institution retrospective study of patients with CRLM who received Y-90
      radioembolization after undergoing molecular testing was performed. Patient
      demographics, systemic therapy regimens, tumor characteristics and overall
      survival were analyzed between patients with differing histopathologic and
      genomic status. PIK3CA, KRAS, NRAS, AKT1, MEK1, MLH1, MSH2, MSH6 and PMS2 were
      analyzed. Kaplan-Meier survival estimation and multivariate Cox regression were
      analyzed. Results: 23 patients underwent genomic analysis prior to Y-90. Eleven
      (47.8%) had mutations identified (MUT), and 12 were sequenced as wild type (WT)
      (52.2%). Median OS of 23 patients after Y-90 was 9.6 months (95% CI 6.67-16.23).
      Median OS from first Y-90 was significantly greater in WT patients (16.2 mo vs
      6.5 mo; p =.0054). The survival difference between poorly differentiated tumors
      compared to all other histologic grades was significant (poor vs. well p=0.025,
      HR=26.8; poor vs. moderate p=.014, HR=23.07; poor vs. moderate/poor p=0.014,
      HR=23.68). When separated into 3 different groups (WT vs. MUT/moderate
      differentiation vs. MUT/poor differentiation) there was a difference in median OS
      observed (16.2 vs. 8.0 vs. 3.8 mos; p<.0001). Imaging response via RECIST
      criteria was significantly different between MUT and WT groups (p=0.02).
      Conclusions: Mutational status and histopathologic grade may predict survival
      after Y-90 radioembolization therapy for CRLM.

PMID- 30197762
TI  - Retraction: MicroRNA-371-5p targets SOX2 in gastric cancer.
AB  - [This retracts the article DOI: 10.18632/oncotarget.8289.].

PMID- 30197763
TI  - Cross-talks between the kidneys and the central nervous system in multiple
      sclerosis.
AB  - Multiple sclerosis (MS) is an inflammatory demyelinating disease, which is
      considered as a common autoimmune disorder in young adults. A growing number of
      evidences indicated that the impairment in non-neural tissues plays a significant
      role in pathology of MS disease. There are bidirectional relationship, metabolic
      activities and functional similarity between central nervous system (CNS) and
      kidneys which suggest that kidney tissue may exert remarkable effects on some
      aspects of MS disorder and CNS impairment in these patients compels the kidney to
      respond to central inflammation. Recently, it has been well documented that
      hormonal secretion possesses the important role on CNS abnormalities. In this
      regard, due to the functional similarity and significant hormonal and non
      hormonal relationship between CNS and kidneys, we hypothesized that kidneys exert
      significant effect on initiation, progression or amelioration of MS disease which
      might be regarded as potential therapeutic approach in the treatment of MS
      patients in the future.

PMID- 30197761
TI  - Approaches to the discovery of non-invasive urinary biomarkers of prostate
      cancer.
AB  - Prostate cancer (PCa) continues to be one of the most common cancers in men
      worldwide. Prostate specific antigen (PSA) measured in blood has been used for
      decades as an aid for physicians to detect the presence of prostate cancer.
      However, the PSA test has limited sensitivity and specificity, leading to
      unnecessary biopsies, overdiagnosis and overtreatment of patients. For these
      reasons, there is an urgent need for more accurate PCa biomarkers that can detect
      PCa with high sensitivity and specificity. Urine is a unique source of potential
      protein biomarkers that can be measured in a non-invasive way. This review
      comprehensively summarizes state of the art approaches used in the discovery and
      validation of urinary biomarkers for PCa. Numerous strategies are currently being
      used in the discovery of urinary biomarkers for prostate cancer including gel
      based separation techniques, mass spectrometry, activity-based proteomic assays
      and software approaches. Antibody-based approaches remain preferred method for
      validation of candidate biomarkers with rapidly advancing multiplex immunoassays
      and MS-based targeted approaches. In the last decade, there has been a dramatic
      acceleration in the development of new techniques and approaches in the discovery
      of protein biomarkers for prostate cancer including computational, statistical
      and data mining methods. Many urinary-based protein biomarkers have been
      identified and have shown significant promise in initial studies. Examples of
      these potential biomarkers and the methods utilized in their discovery are also
      discussed in this review.

PMID- 30197764
TI  - Cytomegalovirus infection and risk of preeclampsia: A meta-analysis of
      observational studies.
AB  - Background: Cytomegalovirus (CMV) infection is one of the most common infectious
      diseases in pregnant women in terms of global impact and is related with many
      adverse health consequences during pregnancy. For the first time, we performed a
      systematic review and meta-analysis study to evaluate the possible association
      between CMV infection and preeclampsia (PE). Methods: A comprehensive literature
      search to identify the relevant papers published earlier than February 2018 was
      performed in PubMed, ISI (Web of Science), Google Scholar and SCOPUS databases.
      We followed the PRISMA (preferred reporting items for systematic reviews and meta
      analyses) guidelines for design, analysis and interpretation of results. Pooled
      odds ratio (OR) and 95% confidence intervals (CI) were estimated using a random
      effects meta-analysis model. Heterogeneity was assessed with Q-test and I2
      statistics. Results: A total of 13 studies including 6158 pregnant women (2734
      women with PE and 3424 healthy controls) met the eligibility criteria. The
      results of meta-analyses based on PCR (OR: 3.09; 95% CI:0.72-13.24; I2=57.3%),
      IgG-ELISA (OR: 1.24; 95% CI:0.83-1.85; I2=71%) and IgM-ELISA (OR: 1.04; 95%
      CI:0.66-1.65; I2=0.0%) demonstrated that CMV infection could not be a potential
      risk factor for PE. Conclusions: In conclusion, results of the present study
      demonstrated that CMV infection could not be a potential risk for developing PE.
      More epidemiological and experimental studies are needed to investigate the
      impact of CMV infection on the development of PE.

PMID- 30197765
TI  - Efficacy of different doses of ketamine as a bolus in major depressive disorder.
AB  - Background: Major depressive disorder is a severe, heterogeneous, common medical
      illness and a leading cause of disability throughout the world that poses a
      significant public health issue. Previous studies have shown rapid antidepressant
      effects following a single administration of ketamine. This study aimed to assess
      the impact of route of administration and dose of ketamine for the reduction of
      depressive symptoms and compare the effects of different doses and methods.
      Methods: A double-blind clinical controlled trial was done on 100 patients with a
      primary diagnosis of major depressive disorder who were assigned into two groups
      of 50 subjects at a dose of 0.5 mg/kg and 0.75 mg/kg ketamine and each group was
      divided into two groups of 25 subjects following a single dose of intravenous
      bolus and infusion of ketamine. The patient's severity of depression was
      evaluated with Hamillton Depression Rating Scale and Beck Depression Inventory
      scores after 2 days, 7 days, 30 days and 60 days of ketamine administration, then
      the results were compared between groups. Results: According to Hamilton and Beck
      score, the treatment response in investigated patients was 64% and 60%,
      respectively. Conclusions: These data suggest that ketamine effect is related to
      drug dose and type of administration. The dose of 0.75 mg/kg of ketamine is more
      effective than 0.5 mg/kg and a bolus injection of low-dose ketamine (0.5 mg/kg)
      is more effective than infusion and in high-dose ketamine (0.75 mg/kg), there was
      no difference between the methods of drug administration.

PMID- 30197766
TI  - Benefits of omalizumab on anxiety and depression in patients with severe asthma.
AB  - Background: Asthma is one of the most common chronic diseases and may cause
      psychiatric disorders affecting the patients' quality of life. In our study, we
      evaluated the effect of omalizumab treatment on anxiety disorder and depression
      using Beck Depression Scale (BDS) and State Trait Anxiety Inventory (STAI).
      Methods: Anxiety level was determined with STAI, whereas depression level was
      evaluated by BDS. Patients were asked to mark the questionnaires to reflect their
      emotional state before treatment, and to reflect their emotions they are feeding
      in the current moment. All patients receiving omalizumab treatment were included
      in the study. Patients with known neuropsychiatric disorder were excluded from
      the study. Results: A total of 20 patients with mean age of 50.25 years were
      enrolled in the study. Gender distribution was: 5(25%) male patients and 15(75%)
      female patients. All patients with severe asthma received omalizumab treatment.
      The omalizumab treatment period was shown for mean 17.6 months (2-40 months). In
      anxiety scales, there was statistically significant difference compared with
      pretreatment and posttreatment periods. Depression (moderate to severe) was
      present in 12 patients before omalizumab treatment and 3 patients after
      omalizumab treatment. Conclusions: Uncontrolled asthma as a chronic disorder can
      cause depressive symptoms and worsen quality of life. We believe by controlling
      asthma, quality of life will improvein such patients. In appropriate indication,
      omalizumab can improve depression and anxiety in asthma patients.

PMID- 30197767
TI  - Serum ferritin levels and bone mineral density in the elderly.
AB  - Background: Iron overload influences negatively on bone mineral density (BMD) but
      the results of studies regarding serum ferritin (SF) and BMD are conflicting.This
      study aimed to determine the association of SF and BMD in the elderly. Methods:
      All participants of the Amirkola cohort selected between 2011-2012, aged > 60
      years were classified as high or normal (<200ng/ml) SF. BMD at femoral neck and
      lumbar spine was determined by dual energy x-ray absorptiometry (DXA) and the
      results were expressed as BMD g/cm2 and BMDT-score. Multiple logistic regression
      analysis with calculation of odds ratio (OR) and 95% confidence interval was used
      to estimate the association of low BMD (LBMD) defined as BMD T-score < -1 with
      SF. Results: 1089 subjects (women, 44.7%) were studied. High SF was observed in
      366 (33.6%) and LBMD in 874 (80.2%) subjects. The two groups of SF were similar
      regarding biochemical parameters and demographic characteristics except MetS,
      overweight /obesity and diabetes which were more prevalent in high SFgroup. BMD
      g/cm2 at both measurement sites was significantly higher (P=0.001 for both) and
      the prevalence of LBMD was significantly lower (74.1% vs 83.1%, P=0.001) in high
      SF group by OR= 0.60 (0.44-0.81). After adjustment for all biochemical and
      demographic variables, the association remained significant by adjusted OR= 0. 68
      (0.49-0.94). Conclusions: These findings show a negative association between high
      SF and LBMD indicating a beneficial effect of high SF in the elderly. Regarding
      detrimental effect of iron overload on bone mass, these findings require further
      studies.

PMID- 30197768
TI  - Q-T interval prolongation in cirrhosis: Relationship and severity.
AB  - Background: Cirrhosis as the final stage of progressive fibrosis of liver can
      affect other organs such as lungs, kidneys and heart. "Cirrhotic cardiomyopathy"
      involves the electrophysiological abnormalities such as QT interval prolongation.
      We assessed correlation between corrected QT interval prolongation and severity
      of cirrhosis based on Child Classification in each ECG lead. Methods: In this
      case-control study, the patients attending the outpatient clinic and inpatient
      department of internal medicine of Velayat Hospital in Qazvin were enrolled from
      September 2014 to July 2015. Total samples were 74 patients, half of which were
      used as controls. Cirrhosis severity was determined as per Child Classification.
      Both groups had Ca2+, Mg2+, K+ tested and 12- lead ECG was obtained. The QT
      interval was corrected by two different formulas: (1) QTc=QT/?RR (QTc1); (2)
      QTc=QT+1.75 (heart rate-60) (QTc2). To analyze the data, the software SPSS
      Version 16 and Mann-Whitney, Pearson's chisquare test-Kruskal-Wallis, and t-tests
      were used. Results: The mean of QTc1 and QTc2 was longer in cirrhotics than the
      control group. There was a significant correlation between Child score and length
      of QTc1 in leads: III (p=0.032), AVL (p=0.041), V2 (p=0.049), V6 (p=0.015). There
      were significant differences in length of QTc1 in leads: V3 (p=0.031) and V6
      (p=0.021); and QTc2 in lead V3 (p=0.039) between Child Classification.
      Conclusions: Cirrhosis can induce QTc interval prolongation. Lead V3 has
      statistically significant correlation with the severity of cirrhosis based on
      child classification. We propose that QT interval prolongation be added as a
      criterion for prioritizing liver transplantation.

PMID- 30197770
TI  - Metabolic syndrome and different obesity phenotypes in the elderly women
      population: Iran's Health System on aging.
AB  - Background: Current literature has been focused on types of obesity with normal
      BMI (body mass index), but metabolically unhealthy.This study evaluates the
      prevalence of metabolical phenotypes of obesity. We also identified the best
      obesity index in predicting the components of metabolic syndrome (MetS). Methods:
      A cross-sectional study has been conducted on 164 women over 60 years.
      Anthropometric parameters, body fat percentage (%BF), and biologic criteria were
      measured to assess the types of obesity. Unhealthy metabolic was defined by
      modified Adult Treatment Panel III, and obesity based on BMI>=25.ANOVA and
      logistic regression were utilized for the association of MetS components and
      obesity phenotypes, and linear regression logistic for finding the best MetS
      related obesity index. Results: The prevalence of metabolically unhealthy was
      45.7%, out of which 33.3% was among the individuals with normal BMI.Logistic
      regression has shown that triglyceride (TG) (OR=3.30, p<0.001) and high density
      lipoprotein (HDL-C) (OR=2.15,p<0.01) was independently related to metabolically
      healthy and normal weight(MHNW) phenotype. Moreover, TG (OR=3.92,p<0.001), HDL-C
      (OR=2.18,p<0.001), fasting blood glucose(FBG) (OR=1.73,p<0.01) and waist
      circumference(WC) (OR=3.18,p<0.001) are correlated significantly with
      metabolically unhealthy and overweight/obese (MUO) and also TG (OR=2.88,p<0.001)
      and WC (OR=2.67,p<0.001) with metabolically unhealthy and
      overweight/obese(MHO).WC followed by %body fat (BF) showed to be highly
      correlated with the prognosis of MetS components. Conclusions: There is a high
      prevalence of unhealthy metabolic among the elderly women,even with normal
      weight.There were different associations between MetS components and various
      obesity phenotypes.TG was the most powerful indicator for the prognosis of
      unhealthy metabolic phenotypes which was independently correlated with the WC,
      %BF and BMI.

PMID- 30197769
TI  - Impairment, disability and fatigue in multiple sclerosis.
AB  - Background: Identifying the predictors of pain is important for both health
      professionals and researchers, because pain has repeatedly been found to be a
      strong predictor of activity limitations and participation restrictions. The
      objective of this study was to determine the predictors of pain presence and
      severity in a large, well-designed sample of community dwelling individuals with
      multiple sclerosis (MS). Methods: This was a cross-sectional study. A center
      stratified random sample including 188 persons with MS were recruited from three
      major MS clinics in the Greater Montreal, Canada. Main outcomes included pain
      prevalence and severity. Predictor variables included depression, anxiety,
      perceived health status, fatigue, sleep problems, and perceived cognitive
      deficits. Participants completed three questionnaires: the first asked about the
      socio-demographic and clinical information of the subjects, the second assessed
      the pain characteristics of the subjects, and the third covered the predictor
      variables. Results: The prevalence of pain in our sample was 42%. MS- related
      disability was found to be in the main predictor for both pain presence and
      intensity. Fatigue also was a main contributor to pain presence. The results of
      this study also showed that pain was associated with higher levels of depression,
      anxiety, sleep problems, and perceived cognitive deficits, and diminished
      perceived health status. Conclusions: The results of this study indicated that
      pain is a common symptom among people with MS. Pain presence was predicted by MS
      related disability and fatigue, while pain intensity was only predicted by MS
      severity.

PMID- 30197771
TI  - Insulin resistance and adverse metabolic profile in overweight/obese and normal
      weight of young women with polycystic ovary syndrome.
AB  - Background: Polycystic ovary syndrome (PCOs) is an endocrine-metabolic disorder.
      This study intends to determine the comparison of insulin resistance (IR) and
      metabolic disturbance in overweight/obese and normal-weight of young women with
      polycystic ovary syndrome. Methods: Using a comparative cross-sectional study
      design in 2015, 27 normal weight (18<BMI<25) and 85 overweight/obese (BMI>=25)
      aged 18 and 35 underwent clinical measures of HOMA (IR) as insulin resistance and
      QUICKI as insulin sensitivity tools in Fatemezahra Infertility Research Center of
      Babol. Lipid profile and hormonal parameters were evaluated between two groups.
      Results: 112 women with PCOS participated in this study. The mean age was 22.4+/
      3.48 years in the normal PCOS group (n=27) and 24.4+/-5.06 years in the
      overweight/obese PCOS patients (n=85). BMI had a significant straight correlation
      with insulin resistance (p<0.001) and a negative correlation with insulin
      sensitivity (p<0.001). BMI showed a straight stronger correlation with
      triglyceride (TG) (p<0.001) and LDL cholesterol (<0.05) and a stronger reverse
      relationship with SHBG (p<0.001). In overweight/obese group, 91.7% (48) of the
      women showed insulin resistance (HOMA>3.15) vs. 8.3% (5) in the normal group
      (P<0.001). 82.4% (62) of the overweight/obese group revealed low insulin
      sensitivity (QUICKI<0.34) while this value was 17.6 % (13) within their lean
      counterparts (p<0.001). In the study group, 89.7 % (54) showed elevated fasting
      insulin concentration (>13uU/ml) vs. 10.3% (7) in the control group (p<0.001).
      Conclusions: Overweight/obese PCOs patients revealed higher insulin resistance
      and lower insulin sensitivity, and also greater TG and LDL cholesterol. Priority
      of management of insulin resistance and lipid profile should be considered on
      identifying these potentially major complications.

PMID- 30197772
TI  - Lifestyle patterns in the Iranian population: Self- organizing map application.
AB  - Background: The present study evaluated the lifestyle behavior patterns and its
      associations with demographic factors in the Iranian population. Methods: A total
      of 8244 people aged 25-70 years who participated in a national survey in 2011
      were included in the study. Factors related to lifestyle (such as diet, physical
      activity, and tobacco use) have been collected using a questionnaire. A self
      organizing map was used for cluster analysis and a multinomial logistic model was
      used for assessment of associations. Results: Seven clusters were identified as
      the following: cluster 1 (15.84%): healthiest lifestyle; cluster 2 (12.45%):
      excessive consumption of sweet tasting soft drinks, salt, and fast food; cluster
      3 (33.73%): no recreational physical activity; cluster 4 (6.86%) alcohol
      consumption, smoking, and consumption of sweet tasting soft drinks; cluster 5
      (14.18%): less salt and oil intake and lack of physical activity; cluster 6
      (7.85%): no use of dairy products; cluster 7 (9.08%): the most unhealthy
      lifestyles; excessive work-related physical activity and smoking and unhealthy
      diet. Male gender was associated with higher odds of being in clusters 4 and 7.
      Individuals who were in unhealthy lifestyle clusters were mostly less educated
      and more self-employed or laborers. Conclusions: A very small percentage of
      individuals was in the healthy lifestyle cluster yet they had poor nutrition.
      Health policy-makers should pay more attention to low recreational physical
      activity among elder people and in middle-aged and housekeepers, and also to high
      work-related physical activities that have a strong tendency to be in a cluster
      with smoking among workers and less educated men.

PMID- 30197773
TI  - Obstructive sleep apnea and severity of coronary artery disease.
AB  - Background: It has been implicated that obstructive sleep apnea (OSA) is
      associated with increased risk of cardiovascular disease including stroke,
      myocardial infarction, coronary artery disease (CAD) and hypertension. The aim of
      this study was to investigate the correlation between OSA and severity of
      atherosclerosis assessed by angiography. Methods: This study included 337
      patients undergoing diagnostic coronary angiography at Tehran Heart Center, Iran.
      The Gensini score was obtained from each patient for coronary angiogram, and OSA
      were assessed by using Multivariable apnea prediction (MAP) risk index on the day
      of cardiac catheterization. The Gensini scores increased in accordance with
      increases in the MAP value. Results: The prevalence rates of three-vessel disease
      were 68.0% in OSA group and 32.0% in non-OSA group. The MAP index was the most
      significant independent determinant for the Gensini score. Conclusions: The
      independent association between OSA and CAD, even after adjustment for
      traditional confounders, suggests that, OSA should be taken into account when
      considering risk factors for CAD.

PMID- 30197774
TI  - Manual therapy in the treatment of carpal tunnel syndrome in diabetic patients: A
      randomized clinical trial.
AB  - Background: Generally, conservative interventions including physiotherapy
      modalities and manual therapy have been recommended in the management of carpal
      tunnel syndrome (CTS), but this subject has not been studied in diabetic patients
      with CTS. Therefore the aim of this study was to investigate the effects of
      manual therapy on diabetic patients with CTS. Methods: Thirty diabetic patients
      with CTS were randomly divided into two equal groups: modality group and manual
      therapy group. Participants in the modality group received transcutaneous
      electrical nerve stimulation (TENS) and therapeutic ultrasound (US) and patients
      in the manual therapy group received manual techniques for the median nerve and
      its surrounding structures. Interventions were applied 3 times weekly for 4 weeks
      in both groups. Visual analogue scale (VAS), symptom severity scale (SSS),
      functional status scale (FSS) and median neurodynamic test (MNT) were evaluated
      before and after the interventions in both groups. Paired t-test and independent
      t-test were used for statistical analysis. Results: Paired t-test revealed that
      all of the outcome measures had a significant change in the manual therapy group,
      whereas only the VAS and SSS changed significantly in the modality group at the
      end of 4 weeks. Independent t-test showed that the variables of SSS, FSS and MNT
      in the manual therapy group improved significantly greater than the modality
      group. Conclusions: Manual therapy techniques applied to mechanical interface of
      the median nerve and nerve mobilization possess more appropriate and valuable
      effects on hand difficulties than modalities in diabetic patients with CTS.

PMID- 30197776
TI  - Antibiotic prophylaxis in the prevention of urinary tract infection in patients
      with sterile urine before extracorporeal shock wave lithotripsy.
AB  - Background: One of the lithotripsy complications is urinary tract infection (UTI)
      and sepsis after extracorporeal shock wave lithotripsy (ESWL). The aim was to
      study the prophylactic effect of antibiotics on UTI after ESWL. Methods: This
      randomized double-blind clinical trial was carried out on 600 patients admitted
      to Babol Clinic hospital in 2014-2015. Patients were randomly divided into
      treatment group (receiving 200 mg ofloxacin and control group (receiving placebo.
      The effect of prophylactic antibiotics on the incidence of bacteriuria after ESWL
      and the impact of variables such as gender, age, urolithiasis size and location
      and underlying diseases in the incidence of UTI after ESWL were evaluated.
      Results: Totally, 67 of the population had positive urine cultures. Twenty-nine
      (10.13%) of them were in the treatment group (n=286) and 38 (13.01%) of them were
      in the control group (n=292). All 67 patients had asymptomatic bacteriuria.
      Escherichia coli and proteus were the grown microorganisms in most samples. The
      mean age of sample population was 44.8+/-23, and 67.16% of patients with positive
      urine culture were older than 45 years. Conclusions: The results indicated that
      prophylactic antibiotics prior to ESWL in patients with urinary calculi and
      negative urine culture had no significant decrease in urinary tract infection
      after lithotripsy. It is better that the use of prophylactic antibiotics is
      limited to patients with risk factors.

PMID- 30197775
TI  - Glomerular filtration rate determination by creatinine and cystatin-C in patients
      with acute pyelonephritis.
AB  - Background: Measurement of glomerular filtration rate (GFR) and monitoring of it
      in any patient on nephrotoxic drugs is very important. Recently, cystatin C (cys
      C) has been introduced as a better marker for determining and monitoring renal
      function than creatinine especially in a mild decrease of GFR. This study was
      done to assess the change of GFR measurement based on serum Cys-C and creatinine
      and their comparison in children with acute pyelonephritis on amikacin. Methods:
      All children with acute pyelonephritis who were admitted in Nephrology ward were
      enrolled in this study. Serum creatinine, serum cys-C and the GFR calculation
      based on them were measured in patients on the day of admission (day zero) and
      then on days 3 and 7 after the start of treatment with amikacin and p-value less
      than 0.05 was considered significant. Results: Among the 70 children, 61 patients
      were females and the others were males. Mean age was 42.66+/-41.53 months.
      Estimated GFR based on creatinine on day 0 (before amikacin administration), 3
      and 7 were 72.41+/-20.89 ml/min/1.73 m2, 78.42+/-21.15 ml/min/1.73 m2 and 80.5+/
      22.43 ml/min/1.73 m2, respectively. Moreover, GFR based on cys-C during these
      days were 116.23+/-58.9 ml/min/1.73 m2, 116.49+/-53.31 ml/min/1.73 m2 and
      108.37+/-51.02 ml/min/1.73 m2, respectively (p<0.05). Conclusions: According to
      this study, decrease of GFR calculation based on Cys-C was seen and estimated GFR
      was not changed according to creatinine. So, we recommend the use of cys-C for
      the monitoring of renal function in any patient treated with nephrotoxic drugs
      such as amikacin.

PMID- 30197777
TI  - Pacemaker lead endocarditis with hiccups (Kalayci).
AB  - Background: Lead-related infections that might develop after pacemaker
      implantation associated with high mortality and morbidity rates are challenging
      to manage and pose high-cost. Patients with lead-related infections usually
      present with fever, chills and fatigue and the treatment can be challenging
      unless the implant system is extracted. Case presentation: A 66-year old male
      patient who underwent dual chamber pacemaker and implantable cardioverter
      defibrillator was admitted to the emergency service with a six-week history of
      complaints of hiccups and fever. After a detailed investigation, lead-related
      infective endocarditis was the diagnosis. The patient was initiated on antibiotic
      therapy and lead extraction was performed. Conclusions: Patients with signs of
      infection who underwent pacemaker implantation may present with atypical symptoms
      such as hiccup. In these cases, imaging, particularly echocardiography, should be
      performed as soon as possible and the localization of the pacemaker leads and
      signs of infective endocarditis should be investigated.

PMID- 30197778
TI  - Reparative radiological changes of hip joint after TNF inhibitors in ankylosing
      spondylitis.
AB  - Background: Hip involvement in ankylosing spondylitis (AS) is a common
      extraspinal arthritic manifestation, which is associated to a worse functional
      outcome. Little data are available on the effectiveness of conservative treatment
      strategies. The TNF inhibitors have been proven effective on AS activity
      parameters. Their structural effect on hip disease however, little is studied.
      Case presentation: We describe four new cases of reparative changes of a damaged
      hip joint after treatment with TNF inhibitors. The average of age was 32.5 (27-
      36) years. There were 3 men and 1 woman. Hip involvement was bilateral in all
      cases. Etanercept was prescribed in 3 cases and infliximab in 1 case. At
      baseline, all patients had a painful and limited hip with high disease activity
      and an important functional impairment. After an average of 5.5 years of
      treatment with TNF inhibitors, the BASRI hip evaluated in antero-posterior x-rays
      of the pelvis remained unchanged at 2.4. The average of mean hip joint space was
      2.9mm (2.3-3.6). A widening in hip joint space was observed in all cases with
      less subchondral cysts. Conclusion: TNF inhibitors seem to be effective on hip
      joint disease in patients with AS.

PMID- 30197779
TI  - Simultaneous bilateral rupture of patellar tendons in diabetic hemodialysis
      patient: A case report.
AB  - Background: Bilateral rupture of the patellar tendon is a very rare injury, which
      takes place in relation to chronic systemic diseases. These injuries are known
      causes. Some of these causes are particular in patellar tendon rupture and
      another are in quadriceps tendon rupture. Case presentation: 70-year-old diabetic
      man with simultaneous bilateral patellar tendon disruption of proximal insertion
      without trauma, receiving long-term hemodialysis. Conclusions: In the present
      study, we report a case of patellar tendon rupture that has two differences with
      literature: first, renal failure is a known risk factor for quadriceps tendon
      rupture, and secondly, the prevalent age of patellar tendon rupture is less than
      40 years. Clinical picture, diagnosis, pathogenesis and treatment are discussed.
      Finally, the literature is reviewed based on previous studies.

PMID- 30197780
TI  - Primary duodenal malignant melanoma: A case report.
AB  - Background: Melanoma is a neoplasm derived commonly from melanocytic cells of
      skin. Although coetaneous presentation of malignant melanoma is easily
      recognizable, the presentation of melanoma in other organs is so confusing. In
      particular, when it metastasizes to other organs, many bizarre figures and
      unusual organs may be involved. In this report, we present a case of primary
      duodenal malignant melanoma. Case Presentation: A 68-year-old man presented with
      a history of iron deficiency anemia. The upper gastrointestinal endoscopy showed
      a prominent papilla of duodenum along with an ulcerative lesion adjacent to
      second part of duodenum. Histopathologic evaluation showed a high-grade malignant
      neoplasm involving the bowel wall which was labeled for S100 protein and markers
      of melanocytic differentiation; Melan-A indicating the definitive diagnosis of
      malignant melanoma of the second portion of duodenal mucosa. Conclusions: In
      patients with a history of iron deficiency anemia, any GI symptom should be
      evaluated carefully. However, the diagnosis of primary GI melanomas in patients
      without any history of melanoma is possible. Full medical investigations are
      recommended in these patients with primary mucosal lesions.

PMID- 30197781
TI  - Pediatric nonalcoholic fatty liver disease.

PMID- 30197782
TI  - Framework for life cycle assessment of livestock production systems to account
      for the nutritional quality of final products.
AB  - Life cycle assessment (LCA) is widely regarded as a useful tool for comparing the
      environmental impacts of multiple livestock production systems. While LCA results
      are typically communicated in the form of environmental burdens per mass unit of
      the end product, it is increasingly becoming recognized that the product quality
      also needs to be accounted for to truly understand the value of a farming system
      to society. To date, a number of studies have examined environmental consequences
      of different food consumption patterns at the diet level; however, few have
      addressed nutritional variations of a single commodity attributable to production
      systems, leaving limited insight into how on-farm practices can be improved to
      better balance environment and human nutrition. Using data from seven livestock
      production systems encompassing cattle, sheep, pigs, and poultry, this paper
      proposes a novel framework to incorporate nutritional value of meat products into
      livestock LCA. The results of quantitative case studies demonstrate that relative
      emissions intensities associated with different systems can be dramatically
      altered when the nutrient content of meat replaces the mass of meat as the
      functional unit, with cattle systems outperforming pig and poultry systems in
      some cases. This finding suggests that the performance of livestock systems
      should be evaluated under a whole supply chain approach, whereby end products
      originating from different farm management strategies are treated as competing
      but separate commodities.

PMID- 30197783
TI  - Effect of vitamin D supplementation on depressive symptoms and psychological
      wellbeing in healthy adult women: a double-blind randomised controlled clinical
      trial.
AB  - Epidemiological evidence has linked low vitamin D status to a range of mood
      disorders. However, studies examining whether vitamin D supplementation can
      improve mood-related outcomes in healthy populations are limited. We investigated
      whether vitamin D supplementation over winter is beneficial for improving mood
      related outcomes in healthy women. A total of 152 healthy women (18-40 years) in
      Dunedin, New Zealand were randomly assigned to receive 50 000 IU (1.25 mg) of
      oral vitamin D3 or placebo once per month for 6 months. They completed the Center
      for Epidemiologic Studies Depression Scale, the anxiety subscale of the Hospital
      Anxiety and Depression Scale and the Flourishing Scale every month. Additionally,
      they reported their positive and negative mood each day for three consecutive
      days every 2 months. Participants provided a blood sample at the beginning and at
      the end of the study for 25-hydroxyvitamin D3 analysis. ANCOVA was used to
      compare the outcome measures between the groups, controlling for baseline. We
      found no evidence of lower depression (P = 0.339), lower anxiety (P = 0.862),
      higher flourishing (P = 0.453), higher positive moods (P = 0.518) or lower
      negative moods (P = 0.538) in the treatment group compared with the control group
      at follow-up. Mood outcomes over the study period were similar for the two
      groups. We found no evidence of any beneficial effect of monthly vitamin D3
      supplementation on mood-related outcomes in healthy premenopausal women over the
      winter period, so recommendations for supplementations are not warranted in this
      population for mood-related outcomes.

PMID- 30197784
TI  - Surgical strategy for suspected early gallbladder carcinoma including incidental
      gallbladder carcinoma diagnosed during or after cholecystectomy.
AB  - Purpose: This paper presents an overview of the surgical strategy for patients
      with suspected gallbladder carcinoma (GBC), including incidental GBC cases,
      preoperatively or intraoperatively, as well as their outcomes. Methods: Between
      April 2009 and December 2017, 529 patients underwent cholecystectomy for
      gallbladder disease at our hospital. Both intraoperative and postoperative
      histological examinations of the excised gallbladder facilitated the diagnosis of
      GBC. Surgery-related variables and surgical approaches were evaluated according
      to the extent of tumor invasion. Results: Of 529 patients, eight were diagnosed
      with GBC during/after cholecystectomy, including four women and four men. Mean
      age was 75.4 (range, 59-89) years. Five patients had gallbladder stones and three
      had cholecystitis. Three patients with stages T1b and T2 underwent additional
      liver bed wedge resections with or without prophylactic common bile duct
      excision. Five of the eight patients are still alive and two of the remaining
      three died from other diseases; one patient with pT3 died of recurrent GBC
      (peritonitis carcinomatosa). Conclusion: Because of the ability to obtain full
      thickness frozen biopsies during laparoscopic cholecystectomy, we could diagnose
      GBC intraoperatively, allowing for rapid diagnosis and tumor resection. We
      recommend developing a surgical treatment strategy for suspected early GBC in
      advance of cholecystectomy.

PMID- 30197785
TI  - A Zero-inflated Beta-binomial Model for Microbiome Data Analysis.
AB  - The microbiome is increasingly recognized as an important aspect of the health of
      host species, involved in many biological pathways and processes and potentially
      useful as health biomarkers. Taking advantage of high-throughput sequencing
      technologies, modern bacterial microbiome studies are metagenomic, interrogating
      thousands of taxa simultaneously. Several data analysis frameworks have been
      proposed for microbiome sequence read count data and determining the most
      significant features. However, there is still room for improvement. We introduce
      a zero-inflated beta-binomial (ZIBB) to model the distribution of microbiome
      count data and to determine association with a continuous or categorical
      phenotype of interest. The approach can exploit mean-variance relationships to
      improve power and adjust for covariates. The proposed method is a mixture model
      with two components: (i) a zero model accounting for excess zeros and (ii) a
      count model to capture the remaining component by beta-binomial regression,
      allowing for overdispersion effects. Simulation studies show that our proposed
      method effectively controls type I error and has higher power than competing
      methods to detect taxa associated with phenotype. An R package ZIBBSeqDiscovery
      is available on R CRAN.

PMID- 30197786
TI  - Synergistic effects of engineered nanoparticles and organics released from laser
      printers using nano-enabled toners: potential health implications from exposures
      to the emitted organic aerosol.
AB  - Recent studies have shown that engineered nanoparticles (ENPs) are incorporated
      into toner powder used in printing equipment and released during their use. Thus,
      understanding the functional and structural composition and potential synergistic
      effects of this complex aerosol and released gaseous co-pollutants is critical in
      assessing their potential toxicological implications and risks. In this study,
      toner powder and PEPs were thoroughly examined for functional and molecular
      composition of the organic fraction and the concentration profile of 16
      Environmental Protection Agency (EPA)-priority polycyclic aromatic hydrocarbons
      (PAH) using state of the art analytical methods. Results show significant
      differences in abundance of non-exchangeable organic hydrogen of toner powder and
      PEPs, with a stronger aromatic spectral signature in PEPs. Changes in structural
      composition of PEPs are indicative of radical additions and free-radical
      polymerization favored by catalytic reactions, resulting in formation of
      functionalized organic species. Particularly, accumulation of aromatic carbons
      with strong styrene-like molecular signatures on PEPs is associated with
      formation of semivolatile heavier aromatic species (i.e., PAHs). Further, the
      transformation of low molecular weight PAHs in the toner powder to high molecular
      weight PAHs in PEPs was documented and quantified. This may be a result of
      synergistic effects from catalytic metal/metal oxide ENPs incorporated into the
      toner and the presence/release of semi-volatile organic species (SVOCs). The
      presence of known carcinogenic PAHs on PEPs raises public health concerns and
      warrants further toxicological assessment.

PMID- 30197787
TI  - "Dopamine homeostasis" requires balanced polypharmacy: Issue with destructive,
      powerful dopamine agents to combat America's drug epidemic.
AB  - The well-researched pro-dopamine regulator KB220 and variants result in increased
      functional connectivity in both animal and human brains, and prolonged
      neuroplasticity (brain cell repair) having been observed in rodents. Moreover, in
      addition to increased functional connectivity, recent studies show that KB220Z
      increases overall brain connectivity volume, enhances neuronal dopamine firing,
      and eliminates lucid dreams in humans over a prolonged period. An unprecedented
      number of clinical studies validating this patented nutrigenomic technology in re
      balancing brain chemistry and optimizing dopamine sensitivity and function have
      been published. On another note, it is sad that unsuspecting consumers could be
      deceived and endangered by false promises of knock-off marketers with look- and-
      sound-alike products. Products containing ingredients having potential dangers
      (i.e., combinations of potent D2 agonists including L-Dopa and L-Theanine)
      threaten the credibility and reputation of validated, authentic, and ethical
      products. We encourage clinicians and neuroscientists to continue to embrace the
      concept of "dopamine homeostasis" and search for safe, effective, validated and
      authentic means to achieve a lifetime of recovery, instead of reverting to anti
      dopaminergic agents doomed to fail in the war against the devastating drug
      epidemic, or promoting powerful D2 agonists that compromise needed balance.

PMID- 30197788
TI  - New developments in immunotherapy for lymphoma.
AB  - The development of immunotherapies for lymphoma has undergone a revolutionary
      evolution over the past decades. Since the advent of rituximab as the first
      successful immunotherapy for B-cell non-Hodgkin lymphoma over two decades ago, a
      plethora of new immunotherapeutic approaches to treat lymphoma has ensued. Four
      of the most exciting classes of immunotherapies include: chimeric antigen
      receptor T-cells, bispecific antibodies, immune checkpoint inhibitors, and
      vaccines. However, with addition of these novel therapies the appropriate timing
      of treatment, optimal patient population, duration of therapy, toxicity, and cost
      must be considered. In this review, we describe the most-promising
      immunotherapeutic approaches for the treatment of lymphoma in clinical
      development, specifically focusing on clinical trials performed to date and
      strategies for improvement.

PMID- 30197790
TI  - Knockdown of long non-coding RNA LCPAT1 inhibits autophagy in lung cancer.
AB  - Objective: Long non-coding RNAs (lncRNAs) are involved in numerous biological
      processes in lung cancer cells. In our previous studies, we identified a lncRNA,
      ENST00000439577, which is highly expressed in lung carcinomas, and termed it lung
      cancer progression-associated transcript 1 (LCPAT1). To characterize the role of
      LCPAT1 in lung cancer, we conducted the current study. Methods: Expression of
      LCPAT1 and autophagy-associated markers in tumor tissues and lung cancer cell
      lines was determined by real-time quantitative polymerase chain reaction (qPCR).
      Hematoxylin and eosin (HE) staining, qPCR, Western blot, and immunohistochemistry
      were performed to evaluate xenografted tumor tissues. Autophagy induced by
      rapamycin was detected by Western blot and immunofluorescence in lung cancer cell
      lines. Results: Expression of LCPAT1 and microtubule-associated protein 1 light
      chain 3 beta (LC3B) was positively correlated in lung cancer. Knockdown of LCPAT1
      inhibited tumor growth and suppressed cell autophagy in vivo. Moreover, LCPAT1
      knockdown in lung cancer cell lines resulted in decreased autophagy-associated
      gene expression and alleviated the cell autophagy induced by rapamycin.
      Conclusions: We speculate that LCPAT1 plays a crucial role in regulating
      autophagy in lung cancer.

PMID- 30197789
TI  - ATM in breast and brain tumors: a comprehensive review.
AB  - The ATM gene is mutated in the syndrome, ataxia-telangiectasia (AT), which is
      characterized by predisposition to cancer. Patients with AT have an elevated risk
      of breast and brain tumors Carrying mutations in ATM, patients with AT have an
      elevated risk of breast and brain tumors. An increased frequency of ATM mutations
      has also been reported in patients with breast and brain tumors; however, the
      magnitude of this risk remains uncertain. With the exception of a few common
      mutations, the spectrum of ATM alterations is heterogeneous in diverse
      populations, and appears to be remarkably dependent on the ethnicity of patients.
      This review aims to provide an easily accessible summary of common variants in
      different populations which could be useful in ATM screening programs. In
      addition, we have summarized previous research on ATM, including its molecular
      functions. We attempt to demonstrate the significance of ATM in exploration of
      breast and brain tumors and its potential as a therapeutic target.

PMID- 30197791
TI  - LncRNA PVT1 promotes ovarian cancer progression by silencing miR-214.
AB  - Objective: Emerging evidence indicates that long non-coding RNAs (lncRNAs) are
      critical in carcinogenesis and progression of ovarian cancer. This study aimed to
      explore the functions and molecular mechanisms of plasmacytoma variant
      translocation I (PVT1) in ovarian cancer. Methods: PVT1 and miR-214 were detected
      by qRT-PCR assays in ovarian cancer tissues and cells. The cell proliferation,
      migration, and invasion abilities were detected by cell functional experiments,
      respectively. Western blot assay was performed to detect epithelial-mesenchymal
      transition (EMT) markers. MiR-214 expression regulated by PVT1 was studied by RNA
      immunoprecipitation (RIP) and chromatin immunoprecipitation (ChIP) assays.
      Results: The expression of PVT1 was up-regulated in ovarian cancer tissues and
      cell lines. Elevated PVT1 expression was associated with advanced stage and
      indicated poor prognosis for ovarian cancer patients. The knockdown of PVT1
      impaired SKOV3 cell proliferation, migration, and invasion in vitro. The
      promotion of ovarian cancer progression by PVT1 involved in regulation of the
      epithelial-mesenchymal transition process and PVT1 interaction with EZH2
      represses miR-214 expression in ovarian cancer cells. Conclusions: PVT1 plays an
      important role in ovarian cancer tumorigenesis, which might be as a novel
      diagnostic marker and therapeutic target for ovarian cancer.

PMID- 30197792
TI  - Increased paracellular permeability of tumor-adjacent areas in 1,2
      dimethylhydrazine-induced colon carcinogenesis in rats.
AB  - Objective: The morphology and functions of the proximal and distal large
      intestine are not the same. The incidence of colorectal cancer in these regions
      is also different, as tumors more often appear in the descending colon than in
      the ascending colon. Inflammatory bowel disease and colorectal cancer can
      increase transepithelial permeability, which is a sign of reduced intestinal
      barrier function. However, there is not enough evidence to establish a connection
      between the difference in colorectal cancer incidence in the proximal and distal
      colon and intestinal permeability or the effects of carcinogenesis on the barrier
      properties in various areas of the colon. The aim of the study was to assess the
      permeability of different segments of the large intestine according to a
      developed mapping methodology in healthy rats and rats with 1,2-dimethylhydrazine
      (DMH)-induced colon adenocarcinoma. Methods: The short circuit current, the
      transepithelial electrical resistance and the paracellular permeability to
      fluorescein of large intestine wall of male Wistar rats were examined in the
      Ussing chambers. The optical density of the solution from the serosa side to
      assess the concentration of the diffused fluorescein from mucosa to serosa was
      analyzed by spectrophotometry. The morphometric and histological studies were
      performed by optical microscopy. Results: Rats with DMH-induced colon
      adenocarcinomas showed elevated transepithelial electrical resistance in the
      areas of neoplasm development. In contrast, there was no change in the
      electrophysiological properties of tumor adjacent areas, however, the
      paracellular permeability of these areas to fluorescein was increased compared to
      the control rats and was characterized by sharply reduced barrier function.
      Conclusions: The barrier properties of the colon vary depending on tumor
      location. The tumors were less permeable than the intact intestinal wall and
      probably have a negative influence on tumor-adjacent tissues by disrupting their
      barrier function.

PMID- 30197793
TI  - Autophagic flux response and glioblastoma sensitivity to radiation.
AB  - Objective: Glioblastoma is the most common primary brain tumor in adults and one
      of the most lethal human tumors. It constitutes a unique non-metastasizing human
      tumor model with high resistance to radiotherapy and chemotherapy. The current
      study investigates the association between autophagic flux and glioblastoma cell
      resistance. Methods: The expression kinetics of autophagy- and lysosome-related
      proteins following exposure of two glioblastoma cell lines (T98 and U87) to
      clinically relevant radiation doses was examined. Then, the response of cells
      resistant to radiotherapy and chemotherapy was investigated after silencing of
      LC3A, LC3B, and TFEB genes in vitro and in vivo. Results: Following irradiation
      with 4 Gy, the relatively radioresistant T98 cells exhibited enhanced autophagic
      flux. The more radiosensitive U87 cell line suffered a blockage of autophagic
      flux. Silencing of LC3A, LC3B, and TFEB genes in vitro, significantly sensitized
      cells to radiotherapy and temozolomide (U87: P < 0.01 and < 0.05, respectively;
      T98: P < 0.01 and < 0.01, respectively). Silencing of the LC3A gene sensitized
      mouse xenografts to radiation. Conclusions: Autophagy in cancer cells may be a
      key factor of radio-resistance and chemo-resistance in glioblastoma cells.
      Blocking autophagy may improve the efficacy of radiochemotherapy for glioblastoma
      patients.

PMID- 30197794
TI  - Coagulation factor VII gene polymorphisms are not associated with the occurrence
      or the survival of hepatocellular carcinoma: a report of 37 cases.
AB  - Objective: : Coagulation factor VII (FVII) triggers the extrinsic pathway of
      blood coagulation. In our previous study, we showed that FVII plays an important
      role in tumorigenesis of hepatocellular carcinoma (HCC). However, the role of
      FVII polymorphism in HCC is still unknown. The present study aimed to investigate
      the relationship between HCC carcinogenesis and single nucleotide polymorphism of
      FVII. Methods: : Thirty-seven HCC patients and 30 healthy donors were recruited
      in this study. Four common FVII gene polymorphisms - a decanucleotide insertion
      at position -323 (-323ins10-bp), a G to T substitution at position -401 (
      401G/T), a G to A substitution at position -402 (-402G/A), and a T to C
      substitution at position -122 (-122T/C) - were analyzed by sequencing or
      commercialized assays using genomic DNA isolated from blood samples.
      Clinicopathological parameters between control and HCC subjects were compared
      according to the specific genotypes. Results: : The most common nucleotide
      variation was -402G/A. However, no statistically significant difference was
      observed between healthy controls and HCC subjects for all four polymorphisms in
      terms of genotype distribution and allele frequencies, indicating that these
      polymorphisms may not affect HCC tumorigenesis. Furthermore, no association was
      found between -402G/A polymorphisms and tumor stage, recurrence, and overall
      survival. Conclusions: : Our results indicate that FVII polymorphisms may not be
      a key factor that clinically impact tumorigenesis and outcomes of HCC, although
      further investigations should be conducted to confirm our findings.

PMID- 30197795
TI  - Analysis of factors related to non-sentinel lymph node metastasis in 296 sentinel
      lymph node-positive Chinese breast cancer patients.
AB  - Objective: Axillary lymph node dissection (ALND) may be unnecessary in 20%-60% of
      breast cancer patients with sentinel lymph node (NSLN) metastasis. The aim of the
      present study was to review the medical records of Chinese patients with early
      stage breast cancer and positive NSLN metastasis to identify clinicopathological
      characteristics as risk factors for non-NSLN metastasis. Methods: The medical
      records of 2008 early-stage breast cancer patients who received intraoperative
      sentinel lymph node biopsy (SLNB) between 2006 and 2016 were retrospectively
      reviewed. These patients were clinically and radiologically lymph node-negative
      and had no prior history of receiving neoadjuvant chemotherapy or
      endocrinotherapy. The clinicopathological characteristics of patients with
      positive NSLN metastasis who underwent ALND were investigated. Results: In the
      present study, 296 patients with positive NSLN metastases underwent ALND.
      Positive non-NSLN metastases were confirmed in 95 patients (32.1%). On univariate
      analysis, >= 3 positive NSLN metastases (P <0.01), NSLN macrometastases ( P =
      0.023), and lymphovascular invasion (P = 0.04) were associated with non-NSLN
      metastasis (P <0.05). In multivariate analysis, the number of positive SLNs was
      the most significant predictor of non-SLN metastasis. For patients with 0, 1, 2,
      or 3 associated risk factors, the non-SLN metastatic rates were 11.5%, 22.5%,
      35.2%, and 73.1%, respectively. Conclusions: The number of positive NSLNs, NSLN
      macrometastases, and lymphovascular invasion were correlated with non-SLN
      metastasis. The number of positive SLNs was an independent predictor for non-NSLN
      metastasis. When 2 or 3 risk factors were present in one patient, the probability
      of non-NSLN was higher than that in the American College of Surgeons Oncology
      Group Z0011 trial (27.3%); thus, avoiding ALND should be considered carefully.

PMID- 30197796
TI  - The prognostic value of programmed cell death ligand 1 expression in non-Hodgkin
      lymphoma: a meta-analysis.
AB  - Objective: Although the prognostic value of programmed cell death-ligand 1 (PD
      L1) expression in non-Hodgkin lymphoma (NHL) has been evaluated in many studies,
      the results remain controversial. To investigate the prognostic role of PD-L1
      expression and the association between PD-L1 expression and clinicopathological
      features of NHL, we performed a meta-analysis. Methods: The PubMed, EMBASE, and
      Cochrane Library databases were searched up to November 30, 2017. The hazard
      ratio (HR), 95% confidence interval (CI), and odds ratios (OR) with 95% CIs were
      combined to evaluate the association of PD-L1 expression with overall survival
      (OS) and clinicopathological features. Review manager 5.3 and STATA 12.0 were
      used in this meta-analysis. Results: A total of 2,005 patients across nine
      studies were enrolled in our meta-analysis, and the pooled results showed that
      high PD-L1 expression was associated with a poor prognosis (HR=2.04, 95% CI: 1.18
      3.54, P=0.01). In the subgroup analysis according to histology types, pooled
      results demonstrated that an increased PD-L1 expression was an unfavorable
      prognostic factor for diffuse large B-cell lymphoma (HR=1.92, 95% CI: 1.06-3.48,
      P=0.03) but not for natural killer/T-cell lymphoma (HR=2.41, 95% CI: 0.47-12.22,
      P=0.29). Pooled ORs indicated that PD-L1 expression was higher in NHL with
      international prognostic indices of >=3. However, PD-L1 expression had no
      correlation with gender, age, disease stage, lactate dehydrogenase level, B
      symptoms, and germinal center B-cell-like lymphoma. Conclusions: High PD-L1
      expression was a poor prognostic biomarker in patients with NHL. Because of our
      limited sample size, high-quality studies with larger sample sizes are needed to
      validate our results.

PMID- 30197797
TI  - Yttrium-90 transarterial radioembolization versus conventional transarterial
      chemoembolization for patients with hepatocellular carcinoma: a systematic review
      and meta-analysis.
AB  - Objective: To compare the effects and safety of conventional transarterial
      chemoembolization (cTACE) and yttrium-90 transarterial radioembolization [TARE
      (90Y)] for hepatocellular carcinoma (HCC). Methods: Nine high-quality
      observational studies, one low bias-risk randomized controlled trial (RCT), and
      one moderate bias-risk RCT included 1,652 patients [cTACE, 1,124; TARE (90Y),
      528], from whom data were extracted for this systematic review and meta-analysis.
      Results: The extracted study outcomes included 1-year and 2-year overall survival
      (OS) rates, objective responses (ORs), and serious adverse events (AEs). 1-year
      OS rates: OR = 0.939, 95 % CI: 0.705-1.251, P = 0.66. 2-year OS rates: overall
      pooled OR = 0.641, 95% CI: 0.382-1.075, P = 0.092; observational study subgroup
      OR = 0.575, 95% CI: 0.336-0.984, P = 0.043; RCT subgroup OR* = 0.641, 95% CI:
      0.382-1.075, P = 0.346. OR: overall pooled OR = 0.781, 95% CI: 0.454-1.343, P =
      0.371; mRECIST subgroup OR = 0.584, 95 % CI: 0.349-0.976, P = 0.040; WHO subgroup
      OR = 1.065; 95% CI: 0.500-2.268, P = 0.870. Serious AEs: overall pooled RR =
      1.477, 95% CI: 0.864-2.526, P = 0.154; RCT subgroup RR = 0.680, 95% CI: 0.325
      1.423, P = 0.306; observational study subgroup RR = 1.925; 95 % CI: 0.978-3.788,
      P = 0.058. Conclusions: TARE (90Y) increased 2-year OS rates in the observational
      subgroup and resulted in better OR rates, according to mRECIST criteria, in
      comparison with cTACE. Furthermore, a lower risk of AEs was observed for TARE
      (90Y) than for cTACE.

PMID- 30197798
TI  - Extracranial metastasis of anaplastic oligoastrocytoma.
AB  - Extracranial metastasis (ECM) of glioma is a rare condition that occurs in the
      internal nervous axis. A 23-year-old woman presented with anaplastic
      oligoastrocytoma (WHO III) in a left temporal tumor. The patient received
      chemoradiotherapy after surgery in our center. Three years after treatment, the
      patient experienced multiple ECMs in the right lung, left iliac bone, and
      multiple swollen subcutaneous nodules including the right clavicle, back of the
      neck, left forearm, right upper arm, and right clavicle. The patient died of
      cerebral herniation at the age of 27 due to recurrent intracranial glioma.
      Treatment of ECM of glioma remains very challenging, and further investigations
      are needed.

PMID- 30197800
TI  - We Would Like to Withdraw Our Manuscript!

PMID- 30197799
TI  - Benefit of everolimus as a monotherapy for a refractory breast cancer patient
      bearing multiple genetic mutations in the PI3K/AKT/mTOR signaling pathway.
AB  - A postmenopausal patient with a diagnosis of estrogen receptor (ER) (+),
      progesterone receptor (PR) (+), and human epidermal growth factor receptor-2
      (HER2) (-) breast cancer was reported. The patient refused surgery and was
      resistant to conventional chemotherapy regimens. Computed tomography and the
      circulating tumor cell test indicated that the patient's tumor burden increased
      rapidly even after several chemotherapy sessions. Multiple genetic aberrances in
      the phosphatidylinositol3-kinases (PI3K) signaling pathway were detected via next
      generation sequencing (NGS)-based liquid biopsy, including a p. G1007R missense
      mutation in exon 21 of PIK3CA (33.61%), a p.L70fs frameshift mutation in exon 3
      of phosphatase and tension homolog deleted on chromosome ten (PTEN) (49.14%), and
      a p. D1542Y missense mutation in exon 32 of mammalian target of rapamycin (mTOR)
      (1.66%). Therefore, only the mTOR inhibitor everolimus was administered to the
      patient. Partial remission (PR) was observed after 2 months, and sustained stable
      disease (SD) was observed after a year and a half. Subsequent sequencing showed
      that the mutation ratio of PIK3CA decreased to 4.17%, and that the PTEN and mTOR
      mutations disappeared, which revealed the significant curative effect of
      everolimus. We report the first case of successful monotherapy treatment using
      everolimus in a patient with advanced breast cancer bearing mutations in genes
      involved in the PI3K/ARK/mTOR signaling pathway. The success of this case
      highlights the invaluable clinical contribution of NGS-based liquid biopsy, as it
      successfully provided an optimal therapeutic target for the patient with advanced
      breast cancer.

PMID- 30197801
TI  - Is There a Change in the Treatment of T1 Glottic Cancer After CO2 Laser? A
      Comparative Study with Cold Steel.
AB  - Objective: Carbon dioxide (CO2) laser provides high local control and disease
      specific survival rates with minor morbidity and good quality of life in
      transoral cordectomy. We aimed to compare the oncological outcome and survival
      between cold steel and CO2 laser in the treatment of early glottic cancer.
      Methods: In this retrospective study, the participants were divided into two
      groups. The first group comprised patients who were operated upon between 2001
      and 2007 using cold steel (group 1, n=38), and the second group comprised
      patients who were operated upon between 2008 and 2016 using CO2 laser (group 2,
      n=88). Both groups were compared regarding age, gender, pathological grade, T
      stage, type of cordectomy, margin status, anterior commissure involvement, follow
      up, locoregional recurrence, and disease-free survival (DFS). Results: The
      overall survival rate and DFS were similar between the two groups (94.7% vs.
      98.9% and 100% vs. 98.9%, respectively), and no association was found between
      surgical margin positivity and local recurrence. However, a significant
      association between the presence of anterior commissure involvement and
      recurrence was found in all 126 patients (p=0.016). Local recurrence was
      significantly higher in the group 2 (p=0.024), but it did not affect overall
      survival and DFS in these patients (100% vs. 94.1%). Conclusion: Although CO2
      laser excision is considered to be superior to cold steel regarding surgical time
      and bleeding control, the local recurrence rates were found to be higher with the
      laser than the cold steel. Thus, we argue that cases should be selected more
      carefully concerning the anterior commissure, depth of tumor invasion lateral to
      vocal muscle, difficulty at endoscopic exposure for lesions with anterior
      commissure involvement, and reliability of surgical margins at frozen sections.

PMID- 30197802
TI  - Investigation of GLUT1, HIF1alpha and TBX21 Gene Polymorphisms in Laryngeal
      Cancer.
AB  - Objective: We aimed to investigate the association of the frequency of three
      single-nucleotide polymorphisms [glucose transporter isoform 1 (GLUT1) reference
      single-nucleotide polymorphism (rs) 710218, hypoxia-inducible factor 1 alpha
      (HIF1alpha) rs11549465, and T-box transcription factor protein 21 (TBX21)
      rs17250932], which have been proved to be related with various benign and
      malignant diseases, with the development of laryngeal cancer and its size and
      grade. Methods: In this study, we included 35 patients with laryngeal cancer and
      35 volunteers at least 30 years old who had smoked for at least 20 years. DNA was
      obtained from the blood samples of the participants using an isolation kit. Then,
      polymorphisms for both the groups were determined using real-time polymerase
      chain reaction. Results: No significant differences were detected regarding the
      genotype and allele frequencies in the three polymorphisms assessed between the
      two groups. In the patient group, on examining the association of polymorphisms
      with tumor size and grade, no significant relation was observed in three
      polymorphisms regarding the related parameters. Conclusion: GLUT1, HIF1alpha, and
      TBX21 polymorphisms have no impact on the development of laryngeal cancer.

PMID- 30197803
TI  - Impact of Hard Palate Angulation Caused by Septal Deviation on Maxillary Sinus
      Volume.
AB  - Objective: To investigate the effect of hard palate angulation caused by septal
      deviation on the volume of the maxillary sinus. Methods: Coronal computed
      tomographic (CT) scans of 1568 patients aged from 18 to 60 were examined. CT
      scans of 402 patients were included in the study. On these scans, the maxillary
      sinus volume, the angle of the nasal septal deviation, and the angulation of the
      hard palate were calculated using the ImageJ software. Each maxillary sinus
      volume was statistically compared with each other and with those in the control
      group. Correlations between palatal angulation and septal deviation were
      determined. Results: Deviated nasal septum whether with or without deflection of
      the hard palate was noted to have caused changes in the volume of the maxillary
      sinus in both female and male patients. The volume of the maxillary sinus on the
      deviated side was less than that of the opposite side, and the differences
      between the volumes of both sinuses were statistically significant (p<0.05). No
      significant differences were noted when compared with the control group. A
      positive correlation was observed between the nasal septal deviation angle and
      the angulation of the hard palate. Conclusion: Regardless of whether or not it
      affects the hard palate, nasal septal deviation reduces the volume of the
      maxillary sinus on the deviated side but does not affect the total volume of the
      maxillary sinuses. Significant differences between the volumes on the two sides
      can lead to facial asymmetry.

PMID- 30197804
TI  - Analyses with the Video Head Impulse Test During the Canalith Repositioning
      Maneuver in Patients with Isolated Posterior Semicircular Canal Benign Paroxysmal
      Positional Vertigo.
AB  - Objective: To evaluate the posterior semicircular canal (PSCC) functions using
      video head impulse test (vHIT) during canalith repositioning maneuver (CRM)
      treatment in patients with isolated, posterior semicircular canal benign
      paroxysmal positional vertigo (PSCC-BPPV). Methods: A total of 44 subjects
      comprising of 24 subjects with isolated PSCC-BPPV and 20 age- and sex-matched
      healthy control subjects were enrolled in the present study. vHIT was performed
      for the affected PSCC before and just after CRM and at the third and seventh day
      and first month to evaluate vestibulo-ocular reflex (VOR) gain, gain asymmetry
      (GA), and corrective saccades. Repeated determinations of VOR gain and GA were
      compared to evaluate the time course of vHIT measurements during CRM treatment in
      isolated PSCC-BPPV patients, and the values were also compared with the control
      group. Results: VOR gains and GA values were not statistically different before
      and after CRM and at the third-day, seventh-day and first-month visits for the
      affected PSCC. Moreover, values did not differ between the BPPV and control
      groups, and none of the subjects demonstrated corrective saccades. Conclusion: To
      our knowledge, this study is the first report to investigate vHIT measurements
      with a time course of alterations during CRM treatment in PSCC-BPPV patients.
      vHIT may not provide an additional contribution for evaluating vestibular
      dysfunction during the diagnosis and treatment of isolated PSCC-BPPV.

PMID- 30197805
TI  - Infrahyoid Flap, a Convenient Alternative for Reconstruction of Tongue and Floor
      of Mouth Defects: Case Series.
AB  - Objective: The aim of this study was to share our clinical experience with the
      neurovascular myofasiocutan infrahyoid flap (NMIHF), which was used for the
      reconstruction of the defects after oral cavity cancer surgery. Methods: Records
      of five patients who were diagnosed with oral cavity cancer and underwent tumor
      resection, neck dissection, and defect reconstruction with NMIHF between 2012 and
      2017 were analyzed retrospectively. Results: The infrahyoid flap was used in five
      patients: four males and one female. The mean age of patients was 61.8 years.
      Four patients underwent tumor resection and bilateral level I-III neck
      dissection, whereas one patient underwent tumor resection and unilateral level I
      III neck dissection. NMIHF was used for the reconstruction of the defects during
      the same procedure in all the patients. Mean post-operative follow-up was 30.6
      months. Partial skin necrosis was observed in two patients, but none of the
      patients showed total necrosis of the flap. Postoperatively, oral intake was
      initiated after an average of 12 days in all patients. For two patients who
      required post-operative radiotherapy (RT), the treatment was started after an
      average of 50 days. Conclusion: NMIHF does not prolong operation time and does
      not cause additional scar in the neck, and the defect in the donor field can be
      closed without the use of a graft or flap. This is considered to be a reliable
      and successful alternative to free flaps for the reconstruction of oral cavity
      defects.

PMID- 30197806
TI  - Assessment of Bone Conduction Thresholds After Surgical Treatment in Patients
      with Labyrinthine Fistula.
AB  - Objective: This study aimed to analyze the bone conduction thresholds before and
      after surgery in chronic otitis media patients with cholesteatoma who had
      labyrinthine fistula and whose cholesteatoma matrix had been completely cleaned.
      Methods: The study was performed between 2013 to 2017 with 23 chronic otitis
      media patients who had labyrinthine fistula with cholesteatoma and who were
      operated at the Department of Otorhinolaryngology of Dicle University School of
      Medicine. Patients were assessed by anamnesis and examination and when necessary,
      by temporal computerized tomography and diffusion magnetic resonance imaging.
      Bone conduction thresholds at frequencies of 500, 1000, 2000, and 4000 Hz were
      determined by audiometric examination and they were compared before and after
      surgery. Results: Of the 23 patients, 12 were female and 11 were male; their age
      range was 10-55 (26.04+/-14.13) years. In the post-operative period, it was
      possible to conduct audiological follow-up on 20 patients. In these follow-ups,
      16 patients showed no change in bone conduction thresholds, two patients showed
      worsening, and two showed improvement. When pre- and post-operative bone
      conduction thresholds at each frequency were compared separately, no significant
      difference was found (p=0.937). No statistically significant difference was found
      between the pre- and post-operative means at the four frequencies (p=0.712).
      Conclusion: In this study, we found that to reduce complications relating to
      cholesteatoma, it might be necessary to completely remove the matrix especially
      in the case of type 1 and 2 labyrinthine fistulas.

PMID- 30197807
TI  - Audiological Results of Total Ossicular Replacement Prosthesis with Cartilage
      Shoe Technique.
AB  - Objective: The aim of this study was to investigate functional results of total
      ossicular replacement prosthesis (TORP) shaft stabilization with a cartilage shoe
      in chronic otitis media patients with cholesteatoma who had undergone canal wall
      down tympanomastoidectomy (CWDT). In addition, it was determined whether the
      presence of granular and edematous mucosa in middle ear altered functional
      outcomes. Methods: Sixty patients, who had undergone CWDT with the use of TORP
      for the reconstruction of ossicular chain, were divided into two groups. Patients
      with cartilage shoe were classified as Group 1 (n=30) and those without the shoe
      were classified as Group 2 (n=30). Patients in both groups were classified into
      "A" and "B" subgroups according to the middle ear risk index (MERI). Air
      conduction (AC) and bone conduction thresholds were evaluated preoperatively and
      postoperatively. Results: There was no statistically significant change between
      preoperative AC thresholds of the groups and subgroups (p>0.05). There were
      statistically significant differences regarding AC thresholds and air-bone gap
      (ABG) values between Groups 1 and 2 at the postoperative 12th month (p<0.05).
      Postoperative AC thresholds and ABG values of Group 1B patients with a high MERI
      score were statistically significant at all frequencies than those of Group 2B
      patients (p<0.05). When ABG values were compared, it was observed that functional
      results were better in Group 1B, but a statistically significant difference was
      observed only at 2000 Hz (p<0.01). Conclusion: The cartilage shoe method for
      titanium TORP stabilization that is used for ossicular reconstruction during CWDT
      has been found to have a beneficial effect on auditory outcomes. Cartilage shoe
      application increases positive effects on hearing outcomes, particularly if the
      middle ear mucosa is granular and edematous.

PMID- 30197808
TI  - Does Nasal Septal Deviation Affect the Eustachian Tube Function and Middle Ear
      Ventilation?
AB  - Objective: Our aim is to evaluate the effect of nasal septal deviation on the
      middle ear pressure and Eustachian Tube (ET) functions with regard to the side of
      deviation. Methods: A prospective randomized clinical trial was conducted.
      Overall, 50 patients (22 female, 28 male) undergoing septoplasty because of nasal
      septum deviation were included. The nasal obstruction symptom evaluation (NOSE)
      scale was used to evaluate surgical satisfaction. Middle ear ventilation and the
      ET functions of a total of 100 ears were assessed with basal tympanometry and
      insufflation tests (Valsalva and Toynbee). The tests were performed on the
      operation day and eight weeks after surgery. The ears were divided into two
      groups: the affected side (the side of nasal obstruction) (Group 1) and the
      contralateral side (Group 2). The study parameters obtained before and after
      septoplasty were compared. Results: The NOSE scores decreased after septoplasty
      (12.48+/-4.78/7.56+/-3.4) (p<0.001). There were 20 functional ETs (40%) in the
      affected side preoperatively, which increased to 36 ears (72%) postoperatively,
      and functional tubes increased to 35 (70%) from 29 (58%) after surgery in the
      contralateral side. The changes in the tympanometry results were statistically
      significant for both the affected side (-33.56 daPA/-21.18 daPA) and
      contralateral side (29.24daPA/-24.96daPA) (p<0.05), but the alteration in the
      side of deviation was more evident. Conclusion: Our study shows that septoplasty
      may have a beneficial effect on middle ear ventilation and ET functions.

PMID- 30197809
TI  - Malignant Otitis Externa: A Retrospective Analysis and Treatment Outcomes.
AB  - Objective: The purpose of this study was to analyze previous treatments and
      outcomes in patients with malignant otitis externa (MOE) retrospectively. The
      efficacy of medical and surgical treatments was also evaluated. Methods: This
      study included 25 patients diagnosed with MOE and treated at the Department of
      Otorhinolaryngology, Ege University School of Medicine between 2006 and 2017. The
      duration of hospitalization, Hemoglobin A1c (HbA1c) levels of the patients,
      erythrocyte sedimentation rate (ESR), source of the infection, complications, and
      previous medical and surgical treatments were also retrospectively assessed.
      Results: The mean age of the patients (7 females and 18 males) was 69.68+/-11.29
      years. The mean length of hospital stay in patients with HbA1c levels <=6 and in
      patients with HbA1c levels >6 was 26.86 and 33.39 days, respectively. The mean
      hospitalization time was significantly longer in patients with HbA1c levels >6
      (p<0.05). Additionally, elderly patients (age>65 years) had a significantly
      longer hospital stay in our study (p<0.05). ESR was found to be 52.76+/-32.49 (9
      108) mm/h at the first examination and 14.92+/-1.22 (4-32) mm/h at the time of
      discharge. Conclusion: MOE is an aggressive disease that requires conservative
      management, and ESR proved to be a good indicator of treatment response. Long
      term antibiotherapy are recommended for treatment.

PMID- 30197810
TI  - The Effectiveness of Botulinum Toxin Type A Injections in the Management of
      Sialorrhea.
AB  - Objective: The aim of this study was to evaluate the effect of Botulinum toxin
      type A by injecting in the submandibular and parotid glands on the frequency and
      severity of sialorrhea. Methods: Pediatric patients who were referred to our
      department with sialorrhea were evaluated using their parents' frequency and
      severity scores of sialorrhea with visual analog scales before and after 3 months
      of botulinum toxin type A injections. Bilateral submandibular and parotid glands
      were injected with Botulinum toxin type A. Results: Twenty-seven pediatric
      patients who were referred to our department with a complaint of sialorrhea were
      included in this study. Seventeen patients were female and 10 were male. Severe
      sialorrhea with cerebral palsy was present in all the patients. There were no
      complications after the procedure. Conclusion: Botulinum toxin A injected in the
      major salivary glands in pediatric patients with neurological disorders is a safe
      and effective method.

PMID- 30197811
TI  - False-Positive Laryngeal FDG Uptake During PET/CT Imaging: Reinke's Edema.
AB  - Positron emission tomography/computed tomography (PET/CT) is frequently used for
      diagnosing, staging, and following-up various malignancy types because it
      provides information on the site and metabolic activity of the tumor.
      Fluorodeoxyglucose (FDG) uptake by the normal laryngeal tissue is symmetric and
      low, whereas that under some non-malignant conditions of the larynx, such as
      vocal cord paralysis and Teflon granuloma, is asymmetrically increased. We
      reported the first case of histologically proven Reinke's edema causing false
      positive laryngeal FDG uptake on PET/CT imaging. A clinician must be aware of
      these rare benign lesions in the case of increased FDG uptake, and
      histopathological investigation is mandatory to rule out malignancy for
      suspicious cases.

PMID- 30197813
TI  - Complications of Formaldehyde Injection for a Cystic Mass of the Neck.
AB  - Formaldehyde is a colorless reactive chemical with suffocating and pungent odor.
      It is irritant to mucous membranes and can enter the body by either oral
      ingestion or inhalation. Formaldehyde is toxic to living tissue. In this report,
      we present the case of a 22-year-old woman who was treated with formaldehyde
      injection for a cystic mass of the neck with developing complications.

PMID- 30197812
TI  - Primary Sinonasal Tuberculosis: A Diagnostic Challenge.
AB  - Primary sinonasal tuberculosis remains a diagnostic challenge as it mimics
      sinonasal granulomatous disease or neoplasms. Its characteristic signs and
      symptoms may be non-specific and highly variable. Here we report a unique
      clinical condition of a 24-year-old man who presented with unilateral nasal
      obstruction and epiphora for 2 years. He was without any comorbidity, was
      immunocompetent, and was otherwise healthy. Subsequent investigations, including
      a computed tomography scan of the paranasal sinuses, and perioperative findings
      revealed a sinonasal mass involving the lateral nasal wall and paranasal sinuses.
      The histopathology was consistent with the features of tuberculosis. There was no
      evidence of pulmonary or any other primary tubercular foci elsewhere in the body,
      suggesting the diagnosis of primary sinonasal tuberculosis.

PMID- 30197814
TI  - A Rare Orbital Complication of Sinusitis in a Pregnant Patient: Orbital
      Inflammatory Granulation.
AB  - Development of orbital inflammatory granulation in pregnant patients as an
      orbital complication of acute sinusitis is extremely rare. Herein, we describe
      the case of a patient with a complication of acute sinusitis that mimicked
      orbital tumors. The patient presented with left orbital protrusion. Magnetic
      resonance imaging revealed pansinusitis with a well-defined mass lesion in the
      extraconal space of the left orbit. Endoscopic endonasal sphenoethmoidectomy and
      orbital decompression were performed. Histopatological examination revealed acute
      inflammatory granulation tissue. To the best of our knowledge, this is the first
      report to describe orbital inflammatory granulation in a pregnant patient as an
      orbital complication of sinusitis.

PMID- 30197815
TI  - Is Adenoidectomy Preventable?

PMID- 30197816
TI  - Erratum.
AB  - [This corrects the article on p. 180 in vol. 55, PMID: 29515932.].

PMID- 30197818
TI  - Conventional Microscopical versus Digital Whole-Slide Imaging-Based Diagnosis of
      Thin-Layer Cervical Specimens: A Validation Study.
AB  - Background: Whole-slide imaging (WSI) has been implemented in many areas of
      pathology, but primary diagnostics of cytological specimens are lagging behind.
      One of the objectives of viewing scanned whole-slide images from histological or
      cytological specimens is remote exchange of knowledge and expertise of
      professionals to increase diagnostic accuracy. We compared the scoring results of
      our team obtained in double readings of two different data sets: conventional
      light microscopy (CLM) versus CLM and CLM versus WSI. We hypothesized that WSI is
      noninferior to CLM for primary diagnostics of thin-layer cervical slides.
      Materials and Methods: First, we determined the concordance rate at different
      thresholds of the participating cytotechnicians by double reading with CLM of 500
      thin-layer cervical slides (Cohort 1). Next, CLM was compared with WSI
      examination of another 505 thin-layer cervical slides (Cohort 2) scanned at *20
      in single focus plane. Finally, all major discordant cases of Cohort 1 were
      evaluated by an external expert in the field of gynecological cytology and of
      Cohort 2 in the weekly case meetings. Results: The overall concordance rate of
      Cohort 1 (CLM vs. CLM) was 97.8% (95% confidence interval [CI]: 96.0%-98.7%) and
      of Cohort 2 was 95.3% (95% CI: 93.0%-96.9%). Conclusion: Concordance rates of WSI
      versus CLM were comparable with those of CLM versus CLM. We have made a step
      forward paving the road to implementation of WSI also in routine diagnostic
      cytology.

PMID- 30197819
TI  - Masculinity and Barebacker Identification in Men who have Sex with Men.
AB  - Purpose: Barebacking is a term that is used to refer to intentional involvement
      in unprotected anal sex. This paper examines the relationship between masculinity
      and self-identification as a barebacker, and how these factors related to HIV
      risk practices in a sample of men who have sex with other men (MSM). Method: As
      part of the Men4Men Study, a brief Internet-based survey was completed in 2007
      with English-speaking MSM aged 18+ who were not involved in a marital/romantic
      relationship at the time of interview. 886 participants were recruited by placing
      electronic postings and banner advertisements on Weblogs, social and sexual
      networking sites, and listservs frequented by MSM. Results: A number of factors
      differentiated men who self-identified as barebackers from those who did not, and
      barebacking identity was linked with greater involvement in HIV risk practices.
      Multivariate analysis revealed that having a high level of masculinity was
      associated with a greater likelihood of self-identifying as a barebacker.
      Conclusions: HIV prevention and intervention efforts targeting MSM ought to
      address issues of self-identification as a barebacker as well as the extent to
      which men adhere to a masculine ideology.

PMID- 30197817
TI  - Examining Joint Effects of Air Pollution Exposure and Social Determinants of
      Health in Defining "At-Risk" Populations Under the Clean Air Act: Susceptibility
      of Pregnant Women to Hypertensive Disorders of Pregnancy.
AB  - Pregnant women are uniquely susceptible to adverse effects of air pollution
      exposure due to vulnerabilities and health consequences during pregnancy (e.g.,
      hypertensive disorders of pregnancy [HDP]) compared to the general population.
      Because the Clean Air Act (CAA) creates a duty to protect at-risk groups, the
      regulatory assessment of at-risk populations has both policy and scientific
      foundations. Previously, pregnant women have not been specially protected in
      establishing the margin of safety for the ozone and particulate matter (PM)
      standards. Due to physiological changes, pregnant women can be at greater risk of
      adverse effects of air pollution and should be considered an at-risk population.
      Women with preexisting conditions, women experiencing poverty, and groups that
      suffer systematic discrimination may be particularly susceptible to cardiac
      effects of air pollutants during pregnancy. We rigorously reviewed 11 studies of
      over 1.3 million pregnant women in the United States to characterize the
      relationship between ozone or PM exposure and HDP. Findings were generally mixed,
      with a few studies reporting a joint association between ozone or PM and social
      determinants or pre-existing chronic health conditions related to HDP. Adequate
      evidence associates exposure to PM with an adverse effect of HDP among pregnant
      women not evident among non-gravid populations.

PMID- 30197820
TI  - Mining FDA resources to compute population-specific frequencies of adverse drug
      reactions.
AB  - Adverse drug reactions (ADRs) represent one of the main health and economic
      problems in the world. With increasing data on ADRs, there is an increased need
      for software tools capable of organizing and storing the information on drug-ADR
      associations in a form that is easy to use and understand. Here we present a step
      by step computational procedure capable of extracting drug-ADR frequency data
      from the large collection of patient safety reports stored in the Federal Drug
      Administration database. Our procedure is the first of its type capable of
      generating population specific drug-ADR frequencies. The drug-ADR data generated
      by our method can be made specific to a single patient population group (such as
      gender or age) or a single therapy characteristic (such as drug dosage, duration
      of therapy) or any combination of such.

PMID- 30197821
TI  - The Use of Imaging in Management of Patients with Low Back Pain.
AB  - Lower back pain (LBP) is one of the most common chief complaints encountered in
      primary care. Advanced imaging studies, including computerized tomography (CT)
      and magnetic resonance imaging (MRI), are frequently ordered in the setting of
      LBP. Structural abnormalities are commonly identified by CT and MRI in patients
      complaining of low back pain, however, these findings are also found in
      asymptomatic patients. In the past decade, multiple guidelines have been
      published to help providers identify patients in whom the use of advanced imaging
      is appropriate. In this article, we review common conditions associated with LBP
      that require advanced imaging along with their clinical and associated imaging
      findings.

PMID- 30197822
TI  - Computed Tomography Evaluation of the Arterial Supply to Segment 4 of the Liver.
AB  - Introduction: In a setting of living-donor liver transplant and patients
      undergoing extended hepatic resections for both primary and metastatic liver
      tumors, preoperative assessment of hepatic arterial anatomy is very important
      because of the risk of ischemic complications in the event of inadvertent injury
      to the arterial supply. Anatomical variations in hepatic arterial supply to the
      liver are very common and seen in nearly half the population. Identifying
      anomalous origin of segment 4 hepatic artery is vital since this vessel can cross
      the transection plane and can result in liver ischemia and liver failure. The
      purpose of our study is to study the variations in hepatic arterial anatomy to
      segment 4 of the liver in the Indian population. Materials and Methods: A
      retrospective evaluation of 637 consecutive computed tomography (CT) angiograms
      over a period of 1 year was performed, and we analyzed the arterial supply to
      segment 4 of the liver. Results: We found that the arterial supply to segment 4
      of the liver originated from left hepatic artery (LHA) in majority of cases,
      76.3%. LHA along with the accessory LHA supplied this segment in 6.4%, whereas
      the accessory LHA solely supplied this segment in 0.4%. The right hepatic artery
      (RHA) was seen to supply this segment in 10.2%. Dual supply with branches from
      the RHA and LHA was seen in 6.6% of patients. Conclusion: Preoperative mapping of
      segment 4 hepatic arterial supply using CT angiography will act as a roadmap to
      surgeons as they attempt to carefully dissect and preserve this segments'
      arterial supply. Depending on the anatomical variation, surgical techniques will
      vary to ensure safety of segment 4 arterial supply.

PMID- 30197823
TI  - Mucinous Neoplasm of the Appendix as a Mimic of Cystic Adnexal Pathology.
AB  - Pelvic pain presents a common diagnostic conundrum with a myriad of causes
      ranging from benign and trivial to malignant and emergent. We present a case
      where a mucinous neoplasm of the appendix acted as a mimic for tubular adnexal
      pathology on imaging. With the associated imaging findings on ultrasound,
      computed tomography, and magnetic resonance imaging, we wish to raise awareness
      of mucinous tumors of the appendix when tubular right adnexal pathology is
      present both in the presence of pelvic or abdominal pain or when noted
      incidentally. Tubular pathology such as uncomplicated paraovarian cysts or
      hydrosalpinx is frequently treated conservatively with long-interval follow-up
      imaging or left to clinical follow-up. Thus, if incorrectly diagnosed as tubular
      pathology, an appendix mucocele or mucinous neoplasm of the appendix is likely to
      be undertreated. We wish to clarify some of the confusion around nomenclature and
      classification of the multiple entities that are comprised by the terms mucocele
      and mucinous tumor of the appendix.

PMID- 30197824
TI  - Unusual Locations of Pancreatic Pseudocysts in Lumbar Triangle, Psoas Muscle and
      Intercostal Space, and Obturator Externus.
AB  - Pancreatic pseudocyst develops as a complication of both acute and chronic
      pancreatitis. Although the common location of pseudocyst is lesser sac, extension
      of pseudocyst can occur into mesentery, retroperitoneum, inguinal region,
      scrotum, liver, spleen, mediastinum, pleura, and lung. Extension of pseudocyst
      into psoas muscle and lumbar triangle is extremely rare. The development of
      pseudocyst in lumbar triangle is radiologically equivalent and further extension
      of Grey Turner's sign seen clinically in acute pancreatitis. This extension
      occurs due to the destructive nature of pancreatic enzymes. The lumbar triangle
      is the site of anatomic weakness in the lateral abdominal wall in the lumbar
      region. We report the case of a 35-year-old alcoholic male patient who presented
      with abdominal pain followed by distension and swelling in the right lumbar
      region for 1 week. On computed tomography scan of the abdomen, acute-on-chronic
      pancreatitis with multiple pseudocysts in the right posterior pararenal space,
      extending through the right lumbar triangle in the right lateral abdominal wall,
      right posterior paraspinal muscles, right iliopsoas, right obturator externus,
      and medial aspect of the right upper thigh, beneath anterior abdominal wall in
      the upper abdomen and in the right lateral thoracic wall through the right 11th
      intercostal space, was detected.

PMID- 30197825
TI  - A Study on the Use of Radiation-Protective Apron among Interventionists in
      Radiology.
AB  - Objective: Radiation-protective aprons are commonly used by interventionists to
      protect against the harmful effects of ionizing radiation. Choice of appropriate
      aprons with respect to lead equivalence and weight is necessary for effective
      protection and reduced physical strain. This study evaluates the knowledge and
      practice of using radiation-protective aprons by interventionists. Materials and
      Methods: Ninety-one interventional radiologists who attended an annual
      interventional conference were provided with a questionnaire which included age,
      years of experience, area of expertise, type and weight of apron used, and
      physical strain caused due to the use of apron. Results: About 14.3% of the
      interventionists practiced in an angiographic suite for less than an hour a day,
      45% for 2-4 h, 21% for 4-6 h, 10% for 6-10 h, and the rest above 10 h/day. About
      68% of the interventionists wore 0.5 mm lead-equivalent (Pbeq) aprons; 15.4% with
      0.25 mm Pbeq; about 5.5% with 0.35 mm Pbeq aprons, and the remaining were not
      aware of the lead equivalence. About 47% reported that they had body aches due to
      wearing single-sided aprons. Interventionists working more than 10 h/day wearing
      single-sided lead apron predominantly complained of shoulder pain and back pain.
      Conclusion: A large fraction of interventionists reported that they had physical
      strain. It is suggestive for interventionists to wear correct fit and light
      weight aprons with appropriate lead equivalence.

PMID- 30197826
TI  - The "Lightning bolt" Sign on Computed Tomography during Percutaneous Renal Mass
      Cryoablation.
AB  - Ice-ball fracture is a rare and often overlooked entity that may lead to
      intraprocedural hemorrhage after percutaneous cryoablation of renal masses. There
      is scant literature on ice-ball fractures associated with percutaneous renal
      cryoablation. Immediate recognition of the lightning bolt sign during
      intraprocedural computed tomography can help identify patients who may have
      developed this complication.

PMID- 30197827
TI  - Clinical Significance of T2*gradient-recalled Echo/susceptibility-weighted
      Imaging Sequences in Evaluating Superficial Siderosis in the Setting of
      Intracerebral Tumors: Pilocytic Astrocytoma.
AB  - Superficial siderosis is the slow accumulation of hemosiderin on the pial
      surfaces of the brain and spinal cord. The most common cause of intracranial
      superficial siderosis is secondary to subarachnoid hemorrhage. Rarely,
      superficial siderosis can also be caused by tumors. Superficial siderosis
      presents clinically as hearing loss and gait instability that progressively
      worsen. The diagnosis is primarily made by magnetic resonance imaging; however,
      susceptibility-weighted imaging (SWI) and T2* gradient echo (GRE) sequences
      demonstrate the highest sensitivity in detecting this condition. To the best of
      our knowledge, there has been only one previous case of superficial siderosis
      secondary to a pilocytic astrocytoma of the spine. However, we present a case of
      intracerebral pilocytic astrocytoma resulting in superficial siderosis, with
      emphasis on acquisition and use of T2*GRE/SWI sequences.

PMID- 30197828
TI  - Contrast-enhanced Computed Tomography Imaging of Splenic Artery Aneurysms and
      Pseudoaneurysms: A Single-center Experience.
AB  - Aim: The aim of our study was to evaluate the computed tomography (CT) imaging
      features of splenic artery aneurysm and pseudoaneurysm and to identify the
      disease conditions related to the same. We also wanted to ascertain any
      relationship between these associated disease conditions and the imaging features
      of the aneurysms. Materials and Methods: This retrospective study included
      patients diagnosed to have splenic artery aneurysms on contrast-enhanced CT
      examination between January 2001 and January 2016. Data were obtained from the
      picture archiving and communication system. The size, number, location,
      morphology, the presence of thrombosis, calcification, and rupture of the
      aneurysms were evaluated. Results: A total of 45 patients were identified with a
      mean age of 45 years. Splenic artery aneurysms were idiopathic in 12 (26.6%)
      patients. In the remaining patients, the main associated disease conditions
      included pancreatitis 15 (33%), chronic liver disease with portal hypertension 8
      (18%), and extrahepatic portal vein obstruction (EHPVO) 6 (13%). Statistically
      significant findings included the relationship between EHPVO and multiple
      aneurysms (P = 0.002), chronic liver disease and fusiform aneurysm (P = 0.008),
      and smaller size of idiopathic aneurysms (P < 0.001). Conclusion: Based on this
      study, splenic artery aneurysms were associated with a variety of etiologies. The
      characteristics of the aneurysms such as size, location, and morphology vary with
      the associated disease conditions. These variations may have implications for the
      management.

PMID- 30197829
TI  - Adding Value to the Magnetic Resonance Examination in a Case of Brachial Plexus
      Birth Palsy.
AB  - We report a case of brachial plexus birth palsy in an infant with the inability
      to move the left upper limb since birth. There was neither history of birth
      trauma nor any complications during delivery. Magnetic resonance imaging (MRI) of
      brachial plexus showed postganglionic injury with musculoskeletal abnormalities.
      The child underwent surgical repair of the plexus and is on physical
      rehabilitation. In this case report, we discuss the utility of a single MRI
      examination with an elaborate discussion on various MRI signs of brachial plexus
      injury including secondary musculoskeletal manifestations. The case reiterates
      the significance of two-in-one approach while imaging these cases with MRI. Apart
      from reporting the damage to the brachial plexus, the radiologist should actively
      search for glenohumeral dysplasia. Awareness of classification and assessment of
      glenohumeral dysplasia should be routinely included as an integral part of
      imaging report as it adds incremental value to the overall patient management and
      functional outcome.

PMID- 30197830
TI  - How far is too far? Understanding identity and overconformity in collegiate
      wrestlers.
AB  - Athletes are expected to distinguish themselves from their peers, make sacrifices
      for the good of the game, play through pain and injury, and push physical and
      mental limits on the path to achieve their goals. Collectively, these
      expectations are known as the 'sport ethic' and while they are considered part of
      sport culture, athletes who overconform to them engage in behaviours that pose
      potentially serious health risks. To explore athlete identity and deviant
      overconformity, this study was designed within a psychocultural life story
      framework using a constructivist-interpretivist paradigm. Three Division I
      wrestlers provided interview data for analysis. Following provisional and
      narrative coding, a word cloud and creative nonfiction were used to present
      results. Participants described a process of overconformity to the sport ethic
      that supported and extended previous research. Results indicated that the
      participants believed that because athletes must push boundaries in order to find
      success, they cannot go 'too far'. Moreover, they reported that their athlete
      identity held significant personal and social meaning to the extent that they
      willingly engaged in forms of deviant overconformity. Recommendations for future
      research include studies with other sport populations (e.g. other sports,
      competitive levels, cultural backgrounds) and the development of an instrument to
      measure athletes' degrees of deviant overconforming. Practitioners may use this
      research to understand the health-compromising behaviours used by their clients
      in an effort to obtain athletic success, which may improve treatment planning and
      outcomes.

PMID- 30197831
TI  - Targeting Prion-like Cis Phosphorylated Tau Pathology in Neurodegenerative
      Diseases.
AB  - Tau is a microtubule-associated protein heavily implicated in neurodegenerative
      diseases collectively known as tauopathies, including Alzheimer's disease and
      chronic traumatic encephalopathy. Phosphorylation of tau at Thr231 allows for the
      isomerization of phosphorylated tau (p-tau) into distinct cis and trans
      conformations. Cis, but not trans, p-tau is detectable not only in Alzheimer's
      disease and chronic traumatic encephalopathy, but also right after traumatic
      brain injury depending on injury severity and frequency both in humans and animal
      models. Cis p-tau is not only neurotoxic but also spreads from a neuron to
      another in a prion-like fashion, functioning as a primary driver of
      neurodegeneration, which can be effectively neutralized by cis p-tau antibody.
      This represents an exciting new opportunity for understanding disease development
      and developing early biomarkers and effective therapies of tauopathies.

PMID- 30197832
TI  - Health Sciences Libraries Advancing Collaborative Clinical Research Data
      Management in Universities.
AB  - Purpose: Medical libraries need to actively review their service models and
      explore partnerships with other campus entities to provide better-coordinated
      clinical research management services to faculty and researchers. TRAIL
      (Translational Research and Information Lab), a five-partner initiative at the
      University of Washington (UW), explores how best to leverage existing expertise
      and space to deliver clinical research data management (CRDM) services and
      emerging technology support to clinical researchers at UW and collaborating
      institutions in the Pacific Northwest. Methods: The initiative offers 14 services
      and a technology-enhanced innovation lab located in the Health Sciences Library
      (HSL) to support the University of Washington clinical and research enterprise.
      Sharing of staff and resources merges library and non-library workflows, better
      coordinating data and innovation services to clinical researchers. Librarians
      have adopted new roles in CRDM, such as providing user support and training for
      UW's Research Electronic Data Capture (REDCap) instance. Results: TRAIL staff are
      quickly adapting to changing workflows and shared services, including teaching
      classes on tools used to manage clinical research data. Researcher interest in
      TRAIL has sparked new collaborative initiatives and service offerings. Marketing
      and promotion will be important for raising researchers' awareness of available
      services. Conclusions: Medical librarians are developing new skills by supporting
      and teaching CRDM. Clinical and data librarians better understand the information
      needs of clinical and translational researchers by being involved in the earlier
      stages of the research cycle and identifying technologies that can improve
      healthcare outcomes. At health sciences libraries, leveraging existing resources
      and bringing services together is central to how university medical librarians
      will operate in the future.

PMID- 30197833
TI  - Measuring Pedestrian Collision Detection With Peripheral Field Loss and the
      Impact of Peripheral Prisms.
AB  - Purpose: Peripheral field loss (PFL) due to retinitis pigmentosa, choroideremia,
      or glaucoma often results in a highly constricted residual central field, which
      makes it difficult for patients to avoid collision with approaching pedestrians.
      We developed a virtual environment to evaluate the ability of patients to detect
      pedestrians and judge potential collisions. We validated the system with both PFL
      patients and normally sighted subjects with simulated PFL. We also tested whether
      properly placed high-power prisms may improve pedestrian detection. Methods: A
      virtual park-like open space was rendered using a driving simulator (configured
      for walking speeds), and pedestrians in testing scenarios appeared within and
      outside the residual central field. Nine normally sighted subjects and eight PFL
      patients performed the pedestrian detection and collision judgment tasks. The
      performance of the subjects with simulated PFL was further evaluated with field
      of view expanding prisms. Results: The virtual system for testing pedestrian
      detection and collision judgment was validated. The performance of PFL patients
      and normally sighted subjects with simulated PFL were similar. The prisms for
      simulated PFL improved detection rates, reduced detection response times, and
      supported reasonable collision judgments in the prism-expanded field; detections
      and collision judgments in the residual central field were not influenced
      negatively by the prisms. Conclusions: The scenarios in a virtual environment are
      suitable for evaluating PFL and the impact of field of view expanding devices.
      Translational Relevance: This study validated an objective means to evaluate
      field expansion devices in reproducible near-real-life settings.

PMID- 30197835
TI  - Application of Pattern Recognition Analysis to Optimize Hemifield Asymmetry
      Patterns for Early Detection of Glaucoma.
AB  - Purpose: To assess the diagnostic utility of a new hemifield asymmetry analysis
      derived using pattern recognition contrast sensitivity isocontours (CSIs) within
      the Humphrey Field Analyzer (HFA) 24-2 visual field (VF) test grid. The
      performance of an optimal CSI-derived map was compared against a commercially
      available clustering method (Glaucoma Hemifield Test, GHT). Methods: Five hundred
      VF results of 116 healthy subjects were used to determine normative distribution
      limits for comparisons. Pattern recognition analysis was applied to HFA 24-2
      sensitivity data to determine CSI theme maps delineating clusters for hemifield
      comparisons. Then, 1019 VF results from 228 glaucoma patients were assessed using
      different clustering methods to determine the true-positive rate. We also
      assessed additional 354 VF results of 145 healthy subjects to determine the false
      positive rate. Results: The optimum clustering method was the CSI-derived seven
      theme class map, which identified more glaucomatous VFs compared with the GHT
      map. The seven-class theme map also identified more cases compared with the five
      , six-, and eight-class maps, suggesting no effect of number of clusters.
      Integrating information regarding the location of glaucomatous defects to the CSI
      clusters did not improve detection rate. Conclusions: A clustering map derived
      using CSIs improved detection of glaucomatous VFs compared with the currently
      available GHT. An optimized CSI-derived map may serve as an additional means to
      aid earlier detection of glaucoma. Translational Relevance: Pattern recognition
      derived theme maps provide a means for guiding test point selection for asymmetry
      analysis in glaucoma assessment.

PMID- 30197834
TI  - Quantification of the Posterior Cornea Using Swept Source Optical Coherence
      Tomography.
AB  - Purpose: We define optical coherence tomography (OCT) measurement parameters of
      the corneal endothelium/Descemet's membrane (DM) complex and peripheral
      transition zone (TZ) and describe these measurements in an ethnically Chinese
      population. Methods: OCT images of the anterior segment and iridocorneal angle
      were obtained from 129 healthy Chinese subjects (129 eyes), aged 40 to 81 years.
      The scleral spur (SS) and Schwalbe's line (SL) were identified in each image.
      Endothelium/DM diameter, referred to as endothelial arc length (EAL), is the SL
      to-SL distance. The SS-to-SL distance encompasses the TZ and trabecular meshwork
      (TM). Since the TZ cannot be visualized by OCT, a ratio of TZ-to-TZ+TM width was
      calculated from scanning electron microscopy (SEM) images obtained from 5
      cadaveric corneas. The SS-to-SL distance was multiplied by this ratio to
      approximate in vivo TZ width. Results: From SEM measurements, the relationship TZ
      = 0.20*(TZ+TM) was determined. From OCT measurements, mean EAL was 12.15 +/- 0.58
      mm and mean TZ width was 156 +/- 20 MUm. For eyes with horizontal and vertical
      images, vertical EAL was significantly greater than horizontal EAL (P = 0.03).
      Conclusions: Corneal endothelium/DM diameter and TZ width can be obtained from
      OCT images. Although only combined TZ+TM is visualized on OCT, TZ width can be
      reasonably approximated. Translational Relevance: Emerging procedures, like
      endothelial cell injection and DM transplantation (DMT), require accurate
      measurements of endothelium/DM size for preoperative planning. Size of the TZ,
      which may contain progenitor cells, also could contribute to endothelial
      regeneration in these procedures.

PMID- 30197836
TI  - Imaging Melanin Distribution in the Zebrafish Retina Using Photothermal Optical
      Coherence Tomography.
AB  - Purpose: To demonstrate and validate that photothermal optical coherence
      tomography (PT-OCT) can image melanin in the retinal pigment epithelium (RPE) and
      can observe light-driven melanosome translocation in the zebrafish retina.
      Methods: A commercial spectral domain OCT system was modified to perform both OCT
      and PT-OCT. Four adult tyrosinase-mosaic zebrafish with varying levels of melanin
      expression across their retinas were imaged, and the PT-OCT signal for pigmented
      and nonpigmented regions were compared. Wild-type dark-adapted (n = 11 fish) and
      light-adapted (n = 10 fish) zebrafish were also imaged with OCT and PT-OCT.
      Longitudinal reflectivity and absorption profiles were generated from B-scans to
      compare the melanin distribution between the two groups. Results: A significant
      increase in PT-OCT signal (P < 0.0001, Student's t-test) was observed in
      pigmented regions of interest (ROI) compared to nonpigmented ROIs in the
      tyrosinase-mosaic zebrafish, which confirms the PT-OCT signal is specific to
      melanin in the eye. A significant increase in PT-OCT signal intensity (P <
      0.0001, Student's t-test) was also detected in the light-adapted wild-type
      zebrafish group compared to the dark-adapted group. Additionally, light-adapted
      zebrafish display more distinct melanin banding patterns than do dark-adapted
      zebrafish in PT-OCT B-scans. Conclusions: PT-OCT can detect different levels of
      melanin absorption and characterize pigment distribution in the zebrafish retina,
      including intracellular changes due to light-driven melanosome translocation
      within the RPE. Translational Relevance: PT-OCT could quantify changes in
      pigmentation that occur in retinal diseases. The functional information provided
      by PT-OCT may also enable a better understanding of the anatomical features
      within conventional OCT images.

PMID- 30197837
TI  - Ultrasound Imaging and Measurement of Choroidal Blood Flow.
AB  - Purpose: The choroid is a vascular network providing the bulk of the oxygen and
      nutrient supply to the retina and may play a pivotal role in retinal disease
      pathogenesis. While optical coherence tomography angiography provides an en face
      depiction of the choroidal vasculature, it does not reveal flow dynamics. In this
      report, we describe the use of plane-wave ultrasound to image and characterize
      choroidal blood flow. Methods: We scanned both eyes of 12 healthy subjects in a
      horizontal plane superior to the optic nerve head using an 18-MHz linear array.
      Plane-wave data were acquired over 10 transmission angles that were coherently
      compounded to produce 1000 images/sec for 3 seconds. These data were processed to
      produce a time series of power Doppler images and spectrograms depicting
      choroidal flow velocity. Analysis of variance was used to characterize peak
      systolic, and end diastolic velocities and resistive index, and their variability
      between scans, eyes, and subjects. Results: Power Doppler images showed distinct
      arterioles within a more diffuse background. Choroidal flow was moderately
      pulsatile, with peak systolic velocity averaging approximately 10 mm/sec and
      resistive index of 0.55. There was no significant difference between left and
      right eyes, but significant variation among subjects. Conclusions: Plane-wave
      ultrasound visualized individual arterioles and allowed measurement of flow over
      the cardiac cycle. Characterization of choroidal flow dynamics offers a novel
      means for assessment of the choroid's role in ocular disease. Translational
      Relevance: Characterization of choroidal flow dynamics offers a novel means for
      assessment of the choroid's role in ocular disease.

PMID- 30197838
TI  - Developments in the Diagnostic Techniques of Infectious Diseases: Rural and Urban
      Prospective.
AB  - Objectives: Diagnostics is the first step for the treatment and eradication of
      infectious microbial diseases. Due to ever evolving pathogens and emerging new
      diseases, there is an urgent need to identify suitable diagnostic techniques for
      better management of each disease. The success rate of specific diagnostic
      technique in any population depends on various factors including type of the
      microbial pathogen, availability of resources, technical expertise, disease
      severity and degree of epidemic of disease in the area. One of the important
      tasks of the policy makers is to identify and implement suitable diagnostic
      techniques for specific regions based on their specific requirements. In this
      review we have discussed various techniques available in the literature and their
      suitability for the target population based on above mentioned criteria. Methods:
      Diagnostic techniques evaluation of well documented representative microbial
      diseases; Tuberculosis (bacterial), Malaria (parasitic) and HIV (viral) were
      included in the study. Identification and collection of information and data was
      performed focusing on the diagnostic techniques used from the scientific
      publications from Pubmed, Science Access, Scopus, EMBASE and several regional
      databases. WHO and CDC database for Tuberculosis, Malaria and HIV were also
      included. These techniques were compared with respect to the financial resource
      availability, expertise and management, functional capacity, pathogen virulence
      and degree of epidemic in the population. Results and Conclusion: In case of
      Tuberculosis, ELISA and colorimetric techniques are successful in rural and urban
      communities with 80% - 90% sensitivity. Genotyping and SNP analysis are useful in
      drug resistant strains. Parasitic disease Malaria also follows the same trend
      with diagnostic techniques like RDTs being common in both population with fast
      results and around 90% sensitivity. STD disease like HIV however shows slight
      different trends due to urgent need of interference in rural epidemics of the
      disease. Rapid and sensitive immunotechniques like dipsticks and agglutination
      with almost 100% sensitivity are used in both rural and urban areas. For the
      confirmation further tests are done like protein Western and NAAT. Advance
      techniques could be the option for higher epidemic area, drug resistance and
      disease research, while rapid techniques would be suitable for low income areas
      and POC facilities. Therefore, suitability of the diagnostic techniques for
      better management depends not only on the financial resources and assessment
      skills of a community but sometimes on the disease itself. We have further
      discussed the technological improvements for specific settings (rural/urban)
      based on the past research for better management of diseases, which could be
      implemented for the understanding of understudied and newly emerging diseases.

PMID- 30197840
TI  - Frequency of Infection during Fever Episodes among Long-Term Care Residents.
AB  - Background: Empirical data regarding the frequency of infection during fever
      episodes among women in long-term care facilities are lacking. Methods: We
      conducted a case-series analysis of women long-term care residents enrolled in a
      randomized trial evaluating cranberry capsules to reduce bacteriuria plus pyuria
      across twenty-one long-term care facilities in CT, USA. Fever episodes identified
      during adverse event surveillance were assessed using established guidelines for
      older adults. Among fever episodes, infections were classified using standardized
      infection surveillance definitions in long-term care residents. Results: We
      identified 123 fever episodes among 80 women long-term care residents. Median age
      was 88 years (range, 65-101), and 81% (N=65) had dementia. Among 123 fever
      episodes, 79 (64%) met criteria for 86 total infections (lower respiratory tract,
      N=43; pneumonia, N=27; gastroenteritis, N=9; urinary tract, N=7). Conclusion:
      Data from this study suggest that approximately two-thirds of fever episodes
      involve infection among women in long-term care facilities. These data may guide
      provider assessments of fever in older adult women in long-term care facilities.

PMID- 30197839
TI  - Vitamin D and Major Chronic Illness.
AB  - OBJECTIVE: To review the current literature regarding vitamin D insufficiency and
      supplementation in major illnesses. DESIGN AND METHODS: We reviewed Pubmed
      indexed, English language manuscripts from January, 2003 to June, 2012 using
      search terms related to vitamin D, all-cause mortality, cardiovascular disease,
      pulmonary disease, diabetes mellitus, and cancer. OUTCOME MEASURES: Incidence of
      disease, risk ratios associated with 25-hydroxyvitamin D [25(OH)D] levels, and/or
      vitamin D supplementation schedules were documented. RESULTS: Although 25(OH)D
      levels >=20 ng/mL were often associated with improved health outcomes, evidence
      suggests that 25(OH)D levels >=30 ng/mL may confer additional health benefits.
      CONCLUSIONS: Based on the available evidence, vitamin D supplementation to
      restore 25(OH)D levels within a range of 30-50 ng/mL is reasonable in order to
      optimize potential benefits and minimize potential risks. This, of course, should
      be considered in the context of individual patient needs and co-morbidities.

PMID- 30197841
TI  - Inositol 1,4,5-trisphosphate Receptor Mutations associated with Human Disease.
AB  - Calcium release into the cytosol via the inositol 1,4,5-trisphosphate receptor
      (IP3R) calcium channel is important for a variety of cellular processes. As a
      result, impairment or inhibition of this release can result in disease. Recently,
      mutations in all four domains of the IP3R have been suggested to cause diseases
      such as ataxia, cancer, and anhidrosis; however, most of these mutations have not
      been functionally characterized. In this review we summarize the reported
      mutations, as well as the associated symptoms. Additionally, we use clues from
      transgenic animals, receptor stoichiometry, and domain location of mutations to
      speculate on the effects of individual mutations on receptor structure and
      function and the overall mechanism of disease.

PMID- 30197842
TI  - Image Quality Evaluation in Clinical Research: A Case Study on Brain and Cardiac
      MRI Images in Multi-Center Clinical Trials.
AB  - Magnetic resonance imaging (MRI) system images are important components in the
      development of drugs because it can reveal the underlying pathology in diseases.
      Unfortunately, the processes of image acquisition, storage, transmission,
      processing, and analysis can influence image quality with the risk of
      compromising the reliability of MRI-based data. Therefore, it is necessary to
      monitor image quality throughout the different stages of the imaging workflow.
      This report describes a new approach to evaluate the quality of an MRI slice in
      multi-center clinical trials. The design philosophy assumes that an MRI slice,
      such as all natural images, possess statistical properties that can describe
      different levels of contrast degradation. A unique set of pixel configuration is
      assigned to each possible level of contrast-distorted MRI slice. Invocation of
      the central limit theorem results in two separate Gaussian distributions. The
      central limit theorem says that the mean and standard deviation of pixel
      configuration assigned to each possible level of contrast degradation will follow
      a normal distribution. The mean of each normal distribution corresponds to the
      mean and standard deviation of the underlying ideal image. Quality prediction
      processes for a test image can be summarized into four steps. The first step
      extracts local contrast feature image from the test image. The second step
      computes the mean and standard deviation of the feature image. The third step
      separately standardizes each normal distribution using the mean and standard
      deviation computed from the feature image. This gives two separate z-scores. The
      fourth step predicts the lightness contrast quality score and the texture
      contrast quality score from cumulative distribution function of the appropriate
      normal distribution. The proposed method was evaluated objectively on brain and
      cardiac MRI volume data using four different types and levels of degradation. The
      four types of degradation are Rician noise, circular blur, motion blur, and
      intensity nonuniformity also known as bias fields. Objective evaluation was
      validated using a proposed variation of difference of mean opinion scores.
      Results from performance evaluation show that the proposed method will be
      suitable to monitor and standardize image quality throughout the different stages
      of imaging workflow in large clinical trials. MATLAB implementation of the
      proposed objective quality evaluation method can be downloaded from
      (https://github.com/ezimic/Image-Quality-Evaluation).

PMID- 30197843
TI  - Design and Integration of an Inexpensive Wearable Mechanotactile Feedback System
      for Myoelectric Prostheses.
AB  - The aim of this paper was to demonstrate the functionality of an inexpensive
      mechanotactile sensory feedback system for transhumeral myoelectric prostheses.
      We summarize the development of a tactile-integrated prosthesis, including 1)
      evaluation of sensors that were retrofit onto existing commercial terminal
      devices; 2) design of two custom mechanotactile tactors that were integrated into
      a socket without compromising suction suspension; 3) design of a modular
      controller which translated sensor input to tactor output, was wirelessly
      adjusted, and fit within a prosthetic forearm; and 4) evaluation of the system
      with a single transhumeral participant. Prosthesis functionality was demonstrated
      over three test sessions; the participant was able to identify tactor stimulation
      location and demonstrated a reduction in grasp force with the mechanotactile
      stimulation. This system offers an inexpensive and modular solution for
      integration of a mechanotactile sensory feedback system into a prosthetic socket
      without compromising the suction seal. These principles can be applied in future
      studies to investigate the direct impact of sensory feedback on tangible outcomes
      for prosthetic users, thereby reducing barriers to clinical translation.

PMID- 30197844
TI  - Effect of Albumin Polymorphism on Thyroid Hormones: A Case Report and Literature
      Review.
AB  - Familial dysalbuminemic hyperthyroxinemia (FDH) is the most common cause of the
      inherited increase of serum thyroxine in Caucasians. This disorder occurs due to
      a missense mutation in the human serum albumin, resulting in an increased
      affinity of thyroxine to the binding sites on the human serum albumin (HSA)
      molecule. HSA is a carrier protein of thyroid hormones and only 10% of thyroxine
      (T4) is bound to human serum albumin, 75% is bound to thyroxine-binding globulin,
      15% to transthyretin, and 0.03% is free. The disorder is characterized by a
      greater elevation of serum thyroxine than triiodothyronine (T3). The high serum
      concentration of T4 is due to the modification of a binding site located in the N
      terminal half of HSA (in subdomain IIA). Arg218 or Arg222 gets replaced with
      smaller amino acids, such as histidine, proline, or serine, due to missense
      mutation; this reduces the steric hindrances in the binding site and creates a
      high-affinity binding site for thyroxine. We herein report a case of FDH with a
      characteristically elevated total T4 and normal free T4 (measured by equilibrium
      dialysis).

PMID- 30197846
TI  - A Case of Herpes Zoster Presented with Lower Limb Paresis.
AB  - Herpes zoster is a common viral disorder that typically shows characteristic
      painful skin lesion. Motor neuropathy rarely complicates herpes zoster infection,
      and it may be overlooked without suspicion. Here, we report a case of a herpes
      zoster patient who presented with sciatica and paresis, but without the typical
      skin lesion. The patient was initially misdiagnosed as having other disorders
      including trauma or spine lesion. Electrodiagnostic study and magnetic resonance
      imaging (MRI) helped to make an accurate diagnosis and localize the motor nerve
      involvement of herpes zoster.

PMID- 30197845
TI  - Meaning of the Solid and Liquid Fascia to Reconsider the Model of Biotensegrity.
AB  - The definition of fascia includes tissues of mesodermal derivation considered as
      specialized connective tissues: the blood and lymph. As water shapes rocks,
      bodily fluids modify the shape and functioning of bodily structures. Bodily
      fluids are silent witnesses to mechanotransductive information, allowing
      adaptation and life, transporting biochemical and hormonal signals. While the
      solid fascial tissue divides, supports, and connects the different parts of the
      body system, the liquid fascial tissue feeds and transports messages for the
      solid fascia. This article reconsiders the model of biotensegrity, by revising
      the definition of solid and liquid fascia, and tries to integrate the fascial
      continuum with the lymph and blood in a new model, because in the previous model,
      these two liquid elements were not taken into consideration. The name given to
      this new model is Rapid Adaptability of Internal Network (RAIN).

PMID- 30197847
TI  - Low Dose Naltrexone and Lung Cancer: A Case Report and Discussion.
AB  - Low dose naltrexone (LDN) has been promising as a complementary medication for
      patients with a broad range of medical disorders. Although not a proven cure,
      evidence from clinical trials supports LDN as being a valuable adjunct for
      disorders in which the immune system plays a centralized role. Additionally,
      clinical trials have proposed a unique mechanism(s) allowing LDN to affect tumors
      including non-small cell lung cancer (NSCLC) at the cellular level by augmenting
      the immune system. We present a case of a 50-year-old male with a prolonged
      survival and a past medical history of prostate and lung cancer.

PMID- 30197848
TI  - Assessment of Validity of SF 36 Questionnaire Using Nepali Language to Determine
      Health-related Quality of Life in Patients with Chronic Liver Disease: A Pilot
      Study.
AB  - OBJECTIVES: The main objective of this study was to translate and validate the
      short form 36 (SF-36) health survey questionnaire into the Nepali language using
      a standard protocol to determine health-related quality of life (HRQoL) in
      patients with chronic liver disease (CLD). METHODS: We conducted a cross
      sectional study among 40 patients with CLD. A formal translation of SF-36 from
      English into the Nepali language was performed. Patients with CLD without other
      known co-morbidities were administered the Nepali version of SF-36. Cronbach's
      alpha and test-retest were performed for reliability analysis. RESULTS:
      Cronbach's alpha of overall SF-36 score was 0.85, and the test-retest correlation
      coefficient was 0.78 (p <0.05). CONCLUSION: The Nepali language version of SF-36
      is valid and reliable.

PMID- 30197849
TI  - Pneumothorax During Cervical Paraspinal Muscle Electromyography: A Case Report.
AB  - Needle electromyography is a common procedure used by physicians to detect an
      underlying neuromuscular disorder. It is performed by inserting a needle
      electrode in different locations of the muscles and measures the muscle reaction
      or electrical activity in response to a nerve's stimulation of the muscle on an
      oscilloscope. The procedure is usually safe, however, in rare cases, the
      insertion of the needle in the pleura or lung can cause a pneumothorax, which can
      be life-threatening. Here, we have reported a case in which a puncture in the
      right cervical paraspinal muscle during a needle electromyography procedure
      caused a right-sided pneumothorax in a 49-year-old female patient who was further
      treated in the hospital until the pneumothorax resolved. In addition, a technique
      that can be used to prevent this life-threatening complication will also be
      discussed. To our knowledge, one similar case report has been presented in the
      past.

PMID- 30197850
TI  - Prosthetic Tricuspid Valve Thrombosis.
AB  - Prosthetic valve thrombosis, a serious complication of prosthetic valve
      replacement, can be lethal without proper treatment. Right-sided valve thrombosis
      is rare but several therapeutic modalities can be considered: anticoagulation
      therapy, fibrinolysis, or surgery. Here, we report a case of significant
      tricuspid valve thrombosis which failed fibrinolytic therapy requiring repeat
      sternotomy with repeat tricuspid valve replacement with a porcine bioprosthesis.

PMID- 30197851
TI  - The Nail Flag Sign: Case Report in a Man with Diverticulitis and Review of
      Dermatology Flag Sign of the Hair, Skin, and Nails.
AB  - A sign is a physical feature or microscopic change which can be observed when the
      patient or their tissue specimen is evaluated. An astute clinician or pathologist
      may be able to diagnose a patient's condition by recognizing this unique
      morphologic feature or pathological change. In dermatology, the flag sign
      alternating transverse bands of the skin or its adnexal structures that are
      analogous to the alternating colors of the stripes of a flag-has been associated
      with distinctive disorders of the hair, skin, or nails. The hair flag sign is
      characterized by alternating horizontal bands of hypopigmentation of the hair (in
      children with kwashiorkor type of protein-calorie malnutrition) or
      hyperpigmentation of the hair (in a male child who has intravenously received
      several cycles of high-dose methotrexate). In skin, the flag sign can be observed
      microscopically in actinic keratosis, and demonstrates by alternating
      parakeratosis and orthokeratosis of the stratum corneum-corresponding to the type
      of hyperkeratosis occurring above the interadnexal epidermis or the ostea of the
      acrosyringia and acrotrichia. The nail flag sign-noted in some individuals who
      have diabetes mellitus, diverticulitis, leprosy, or vitiligo-presents with
      alternating white and pink-red horizontal bands beginning at the proximal nail
      fold and extending distally to the free edge of the nail plate. A man with
      chronic diverticulitis and the nail flag sign is reported; he also has a history
      of congenital leukonychia, actinic keratoses, basal cell carcinoma and psoriasis.
      In addition, the features of hair, skin, and nail flag signs are reviewed. The
      detection of the dermatology flag sign can prompt a pathologist to consider the
      diagnosis of actinic keratosis. Alternating horizontal bands of hair color can
      indicate protein-calorie malnutrition or an effect of chemotherapy in a child.
      Certain autoimmune, inflammatory, or infectious conditions in individuals present
      with white and pink-red horizontal bands on their nails.

PMID- 30197852
TI  - Depression and its Associated Factors among Patients with Chronic Obstructive
      Pulmonary Disease in Karachi, Pakistan.
AB  - Introduction Depression in patients with chronic obstructive pulmonary disease
      (COPD) can be an incapacitating health problem that negatively affects the
      quality of life. If the depression is not treated, it is associated with
      increased morbidity and mortality. The goal of this study was to determine the
      frequency of depression in patients with COPD and examine the factors
      contributing to depression in these patients. Methods This cross-sectional study
      was conducted using a sample of 556 patients with COPD visiting the Pulmonology
      Clinic of the Aga Khan University Hospital in Karachi, Pakistan, from March 2010
      to March 2011. A pretested structured questionnaire was used for data collection.
      The Hospital Anxiety and Depression Scale (HADS) was used to screen for
      depression. SPSS Statistics for Windows, Version 19.0. (IBM Corp, Armonk, NY) was
      used to enter and analyze data. Results Out of the total 556 participants,
      majority 62.9% were between 60 and 79 years of age and 70.1% of the participants
      were males. The frequency of depression in COPD patients was 57.2%, and multiple
      logistic regression analyses indicated being over 59 years (Adjusted odds ratio
      (ORadj), 2.750; 95% confidence interval [CI]: 1.25 to 6.05, p = 0.039), being
      male (ORadj, 2.28; 95% CI: 0.89 to 5.14), being retired or unemployed (ORadj,
      1.041; 95% CI: 0.41 to 2.62, p = 0.000), using inhaled steroids (ORadj, 3.929;
      95% CI: 2.59 to 5.97, p = 0.000), and living alone were significantly associated
      with depression in COPD patients. Conclusion Several risk factors for depression
      in patients with COPD were identified. Patients with COPD who are elderly, male,
      retired or unemployed, use inhaled steroids, and patients who live alone have
      characteristics significantly associated with depression. These factors should be
      considered by practicing family physicians, pulmonologists, and healthcare
      workers.

PMID- 30197853
TI  - Superior Cerebellar Arteries Originating from the Posterior Cerebral Arteries but
      Normal Course of the Oculomotor Nerves.
AB  - The posterior cerebral artery (PCA) is a branch of the terminal part of the
      basilar artery and perfuses the temporal lobes, midbrain, thalamus, and the
      posterior inferior portion of the parietal lobes. It is divided into P1-P4
      segments. Variations in the P1 segment of the PCA are important to neurosurgeons
      when performing surgery, for example, on basilar tip aneurysms. We report
      bilateral superior cerebellar artery (SCA) arising from the P1 segment of the
      PCA. Such a configuration appears to be uncommon but should be kept in mind by
      neurosurgeons, neurointerventionalists, and neuroradiologists.

PMID- 30197854
TI  - Clinical Features of Tourette Syndrome and Tic Disorders.
AB  - Background: Tourette syndrome (TS) is a neurodevelopmental disorder characterized
      by motor and vocal tics--rapid, repetitive, stereotyped movements or
      vocalizations lasting at least one year in duration. The goal of this article was
      to review the long-term clinical course of tics and frequently co-occurring
      conditions in children with TS. Methods: We conducted a traditional literature
      search to locate relevant articles regarding long-term outcome and prognosis in
      TS and tic disorders. Results: Tics typically have an onset between the ages of 4
      and 6 years and reach their worst-ever severity between the ages of 10 and 12
      years. By age 10 years, most children are aware of nearly irresistible
      somatosensory urges that precede the tics. A momentary sense of relief typically
      follows the completion of a tic. Over the course of hours, tics occur in bouts,
      with a regular inter-tic interval. Tics increase during periods of psychosocial
      stress, emotional excitement and fatigue. Tics can become "complex" in nature and
      appear to be purposeful. Tics can be willfully suppressed for brief intervals and
      can be evoked by the mere mention of them. Tics typically diminish during periods
      of goal-directed behavior. Over the course of months, tics wax and wane. By early
      adulthood, roughly three-quarters of children with TS will have greatly
      diminished tic symptoms and more than one-third will be virtually tic free.
      Conclusion: Although tics are the defining aspect of TS, they are often not the
      most enduring or impairing symptoms in children with TS. Indeed in TS tics rarely
      occur in isolation, and other coexisting conditions--such as behavioral
      disinhibition, hypersensitivity to a broad range of sensory stimuli, problems
      with visual motor integration, procedural learning difficulties, attention
      deficit hyperactivity disorder, obsessive-compulsive disorder, depression,
      anxiety, and emotional instability--are often a greater source of impairment than
      the tics themselves. Measures used to enhance self-esteem, such as encouraging
      independence, strong friendships and the exploration of interests, are crucial to
      ensuring positive adulthood outcome.

PMID- 30197855
TI  - Effect of sodium chloride on gene expression of Streptococcus mutans and zeta
      potential of demineralized dentin.
AB  - Purpose: In this work, the effects of sodium chloride (NaCl) on gene expression
      of planktonic Streptococcus mutans cells are investigated. Also assessed are the
      effects of NaCl on zeta potential of sound and demineralized dentin. Methods: The
      relative level of glucosyltransferase B (gtfB), gtfC and gtfD transcription of S.
      mutans in the presence of NaCl was evaluated by quantitative polymerase chain
      reaction (qPCR). The osmolality of varying salt (NaCl) concentrations and their
      influence on the zeta potential of sound and demineralized dentin was
      investigated as well. Results: NaCl significantly reduced the expression of gtfB
      and C genes in planktonic S. mutans; whereas, gtf D gene expression significantly
      increased in the presence of NaCl (P < 0.05). NaCl at concentrations of 37.5
      mg/ml reduced zeta potential of demineralized dentin, while no significant
      decrease of zeta potential was found when sound dentin was exposed to this
      concentration. Conclusion: NaCl reduces the expression of some gtfs in S. mutans
      and increases negative potential charge of demineralized dentin.

PMID- 30197856
TI  - Mutagenicity potential (affect) of new atraumatic restorative treatment (ART)
      material incorporated with Azadirachta indica (Neem) against Salmonella
      typhimurium.
AB  - Background: The mutagenicity potential of a new atraumatic restorative treatment
      (ART) material against Salmonella typhimurium without metabolic activity using
      the Ames test (genotoxicity) was carried out. Methods and materials: The
      potential mutagenicity of new atraumatic restorative treatment materials (ART-I
      and ART-II) was analyzed using the Ames test. The materials were eluted in
      dimethyl sulphoxide, 0.9% NaCl solution and sterilized de-ionized water and the
      aliquots were used after an incubation period of 24 h at 37  degrees C. Mutagenic
      effects of the materials were tested on Salmonella typhimurium strains TA 98 and
      TA 100 using the standard assay, and in absence of S9 fraction from rat liver.
      Result: No mutagenic effects were detected for these new ART materials on S.
      typhimurium TA100. The incubated DMSO extract and 0.9% NaCl extract (50
      MUl/plate) of the ART-I exhibited a weak mutagenic potential on S. typhimurium TA
      98. In particular, Aqua extract (50 MUl/plate) of ART-II, was associated with a
      weak mutagenic potential on S. typhimurium TA98. Conclusion: Both ART materials
      (ART-I and II) exhibited weak mutagenic effects on S. typhimurium TA98 whereas no
      mutagenic effect was detected on S. typhimurium TA100. ART-II is safer than ART
      I.

PMID- 30197857
TI  - Psychometric properties of Hindi version of child oral impact on daily
      performances (C-OIDP) index amongst school children in North India.
AB  - Aim: To assess validity and reliability of Hindi version of Child Oral impact on
      daily performances (C-OIDP) index among school children in North India. Material
      and methodology: Descriptive cross sectional study was conducted amongst 250, 11
      12 year old school children in primary schools of Rishikesh, Uttarakhand, India.
      The study was done in two phases: first phase included assessment of Psychometric
      and linguistic properties of hindi version of C-OIDP index which was then pilot
      tested on study subjects. Phase two comprised of the actual main study which
      included the re-assessment of Hindi C-OIDP index on the entire study population.
      The pilot study comprised of 40 school children while the main study was
      conducted on 250 school children. Results: The inter-item correlation coefficient
      ranged from 0.1 to 0.786 while corrected item total correlation coefficient
      ranged from 0.176 (smiling) to 0.843 ((cleaning). The standardised Cronbach's
      Alpha coefficient was 0.88. Moreover, the alpha coefficients didn't increase upon
      deleting any of the items. Weighted kappa was 0.85 & ICC was 0.9. Children with
      higher scores were less satisfied with their mouth (p- 0.001) in case of
      concurrent validity. Conclusion: Hindi Child Oral Impact on Daily Performances
      index can be used as a valid and reliable instrument in measuring OHRQoL. of
      Paediatric North Indian population.

PMID- 30197858
TI  - Ceramic soft tissue trimming bur: A new tool for gingival depigmentation.
AB  - Objective: Pigmentation of the gingiva plays a negative role in an otherwise
      acceptable "smile window". In the present world, people are more concerned about
      their aesthetics. Several techniques have been employed such as scalpel surgery,
      electrosurgery, cryosurgery, chemical agents, abrasion and LASER method for the
      removal of melanin hyper-pigmentation. The present study is aimed at comparing
      the efficacy of LASER and soft tissue trimmer for gingival depigmentation.
      Methods: A randomized split-mouth study was conducted for twenty patients with
      gingival pigmentation. Dummet Oral Pigmentation Index (DOPI), Gingival
      Pigmentation Index (GPI) for pigmentation, bleeding factor, wound healing factor,
      gingival colour and visual analogue scale (VAS) score for pain were evaluated for
      both the groups at baseline, 7th day, 1st month and 6th month. Results: Intra
      group comparison between baseline and 6th month showed highly significant
      difference for both LASER and bur groups. There was no statistically significant
      difference found between both the groups at 6th month using gingival pigmentation
      index. Conclusion: It can be concluded that LASER and soft tissue trimmer both
      are comparable in achieving aesthetic satisfaction. Hence, the soft tissue
      trimmer could also be used for depigmentation as it is very cost effective,
      readily available and acceptable by the patients.

PMID- 30197859
TI  - Estimation of salivary and serum basic fibroblast growth factor in treated and
      untreated patients with oral squamous cell carcinoma.
AB  - Objective: The purpose of this study was to evaluate salivary and serum basic
      fibroblast growth factor (bFGF) level in OSCC patients to provide a reliable
      biomarker for the early detection, monitoring, and prognosis of OSCC patients.
      Materials and methods: The study enrolled 90 subjects, equally grouped as
      recently diagnosed & untreated OSCC patients (Group I), treated OSCC without any
      recurrence (Group II) & as control (Group III). Enzyme-linked immunosorbent assay
      was employed to measure bFGF concentrations in saliva and serum samples of all
      three groups. The results were tabulated and analyzed statistically. Results:
      Group I showed high-level of bFGF expression profile in saliva (8.80 +/- 1.26
      pg/ml) whereas the levels of bFGF in group II (2.69 +/- 0.17 pg/ml) and Group III
      (3.17 +/- 0.43 pg/ml) are significantly lower than group I. Serum bFGF levels
      were also high in group I (6.33 +/- 0.81 pg/ml) and decreased significantly in
      group II (3.52 +/- 0.45 pg/ml) however, the control group showed elevated range
      of levels (7.63 +/- 0.88 pg/ml). Conclusions: This study demonstrates the
      reliability of salivary bFGF marker as diagnostic as well as prognostic marker.
      Serum bFGF could also be used as prognostic marker only in Oral Squamous cell
      carcinoma patients.

PMID- 30197860
TI  - Analysis of bite marks in food stuffs by CBCT 3D-reconstruction.

PMID- 30197861
TI  - Antifungal efficacy of herbs.
AB  - : Candida carriage was reported to be common in oral cancer patients, with C.
      albicans being the predominant species. The prevalence of diseases caused by
      Candida species have been found to increase in recent years. AIM: The aim of our
      study was to find the antifungal activities at MIC of selected fifteen plant
      leaves extracts prepared in three different solutions (methanol and ethanol)
      against the opportunistic pathogen Candida albicans isolated from oral cavity
      infections. It may also help the clinician to treat the patient not only for the
      particular lesion that is present, but also to treat the infection by Candida
      albicans so as to reduce its potential to malignant transformation. Material n
      methods: Leaves extract of selected plant prepared in methanolic and eethanolic
      solution have been chosen for the investigation of in vitro antifungal activity
      which acts as expectorant and not having toxic properties on humans while for
      comparison or control, antifungal drugs have been taken. Results showed that
      Candida albicans shows most sensitivity towards the standard antibiotic
      cotrimoazol but very less towards other drugs like Fluconazole, minocycline,
      erythromycin respectively which indicated Candida albicans shows some resistance
      character towards drugs while the herbal extracts of Lawsonia inermis, Withania
      somnifer, Curcuma longa, Cymbopogon citrates and Zingiber officinale gives the
      best inhibitory effect and they have the potential to control growth of Candida
      albicans.

PMID- 30197862
TI  - Expression, characterization and one step purification of heterologous glucose
      oxidase gene from Aspergillus niger ATCC 9029 in Pichia pastoris.
AB  - Glucose Oxidase (GOD), is a common flavoprotein from Aspergillus niger ATCC 9029
      with a broad application in biotechnology, food and medical industries. In this
      study, GOD gene was cloned into the expression vector, pPIC9 and screened by the
      alcohol oxidase promoter. The enzyme production increased at 28  degrees C. GOD
      activity induced by 1.0% methanol and the highest level of GOD production was the
      result of shaking rate at 225 rpm. The highest enzyme activity obtained at a pH
      value ranged from 5 to 7 at 50  degrees C. The enzyme was stable at a broad pH
      range and temperature.

PMID- 30197863
TI  - Simultaneous biosynthesis of (R)-acetoin and ethylene glycol from D-xylose
      through in vitro metabolic engineering.
AB  - (R)-acetoin is a four-carbon platform compound used as the precursor for
      synthesizing novel optically active materials. Ethylene glycol (EG) is a large
      volume two-carbon commodity chemical used as the anti-freezing agent and building
      block molecule for various polymers. Currently established microbial fermentation
      processes for converting monosaccharides to either (R)-acetoin or EG are plagued
      by the formation of undesirable by-products. We show here that a cell-free
      bioreaction scheme can generate enantiomerically pure acetoin and EG as co
      products from biomass-derived D-xylose. The seven-step, ATP-free system included
      in situ cofactor regeneration and recruited enzymes from Escherichia coli W3110,
      Bacillus subtilis shaijiu 32 and Caulobacter crescentus CB 2. Optimized in vitro
      biocatalytic conditions generated 3.2 mM (R)-acetoin with stereoisomeric purity
      of 99.5% from 10 mM D-xylose at 30  degrees C and pH 7.5 after 24 h, with an
      initial (R)-acetoin productivity of 1.0 mM/h. Concomitantly, EG was produced at
      5.5 mM, with an initial productivity of 1.7 mM/h. This in vitro biocatalytic
      platform illustrates the potential for production of multiple value-added
      biomolecules from biomass-based sugars with no ATP requirement.

PMID- 30197864
TI  - CO2 to succinic acid - Estimating the potential of biocatalytic routes.
AB  - Microbial carbon dioxide assimilation and conversion to chemical platform
      molecules has the potential to be developed as economic, sustainable processes.
      The carbon dioxide assimilation can proceed by a variety of natural pathways and
      recently even synthetic CO2 fixation routes have been designed. Early assessment
      of the performance of the different carbon fixation alternatives within
      biotechnological processes is desirable to evaluate their potential. Here we
      applied stoichiometric metabolic modeling based on physiological and process data
      to evaluate different process variants for the conversion of C1 carbon compounds
      to the industrial relevant platform chemical succinic acid. We computationally
      analyzed the performance of cyanobacteria, acetogens, methylotrophs, and
      synthetic CO2 fixation pathways in Saccharomyces cerevisiae in terms of
      production rates, product yields, and the optimization potential. This analysis
      provided insight into the economic feasibility and allowed to estimate the future
      industrial applicability by estimating overall production costs. With reported,
      or estimated data of engineered or wild type strains, none of the simulated
      microbial succinate production processes showed a performance allowing
      competitive production. The main limiting factors were identified as gas and
      photon transfer and metabolic activities whereas metabolic network structure was
      not restricting. In simulations with optimized parameters most process
      alternatives reached economically interesting values, hence, represent promising
      alternatives to sugar-based fermentations.

PMID- 30197865
TI  - Harnessing a P450 fatty acid decarboxylase from Macrococcus caseolyticus for
      microbial biosynthesis of odd chain terminal alkenes.
AB  - Alkenes are industrially important platform chemicals with broad applications. In
      this study, we report a direct microbial biosynthesis of terminal alkenes from
      fermentable sugars by harnessing a P450 fatty acid (FA) decarboxylase from
      Macrococcus caseolyticus (OleTMC). We first characterized OleTMC and demonstrated
      its in vitro H2O2-independent activities towards linear C10:0-C18:0 FAs, with
      higher activity for C16:0-C18:0 FAs. Next, we engineered a de novo alkene
      biosynthesis pathway, consisting of OleTMC and an engineered E. coli thioesterase
      (TesA) with compatible substrate specificities, and introduced this pathway into
      E. coli for terminal alkene biosynthesis from glucose. The recombinant E. coli
      EcNN101 produced a total of 17.78 +/- 0.63 mg/L odd-chain terminal alkenes,
      comprising of 0.9% +/- 0.5% C11 alkene, 12.7% +/- 2.2% C13 alkene, 82.7% +/- 1.7%
      C15 alkene, and 3.7% +/- 0.8% C17 alkene, and a yield of 0.87 +/- 0.03 (mg/g) on
      glucose. To improve alkene production, we identified and overcame the electron
      transfer limitation in OleTMC, by introducing a two-component redox system,
      consisting of a putidaredoxin reductase (CamA) and a putidaredoxin (CamB) from
      Pseudomonas putida, into EcNN101, and demonstrated the alkene production
      increased ~2.8 fold. Finally, to better understand the substrate specificities of
      OleTMC observed, we employed in silico protein modeling to illuminate the
      functional role of FA binding pocket.

PMID- 30197867
TI  - A hand-held, power-free microfluidic device for monodisperse droplet generation.
AB  - Here we develop a microfluidic device to generate monodispersion sub-nanoliter
      size droplets. Our system reaches steady state within 3 s after the flow starts
      and generates 100,000 droplets in 28 s with high size consistency (CV < 8%). This
      low cost device is composed with a microfluidic chip, 2 tubings, a collection
      vial, a syringe and a station; and is in the size of an iPad Mini (4" * 6" *
      3/4"). In this system, all incoming reagents share the same pressure drop across
      the fluidic passage to generator droplets. A single source negative pressure is
      applied to the fluids to create the flow by a vacuum at the exit end of the
      device. The vacuum is generated on-site by pulling the plunger of a syringe. The
      position of the plunger before and after pulling determines the degree of vacuum.
      A fixture is used to hold the plunger after it is pulled to maintain its vacuum.
      Although this system loses vacuum gradually as the liquid filling in, it
      maintains a flow rates with the changes less than 10% and droplet sizes changes
      less than 2% during the course of generating 150,000 droplets. The pressure drop
      across the chip, the flow rates of all reagents, the droplet size and generation
      frequency are predictable, programmable, and reproducible. This device is
      designed for generating droplets for single cell genome profiling application but
      can be also used for digital PCR or other droplet-based applications.

PMID- 30197866
TI  - Whole-cell (+)-ambrein production in the yeast Pichia pastoris.
AB  - The triterpenoid (+)-ambrein is a natural precursor for (-)-ambrox, which
      constitutes one of the most sought-after fragrances and fixatives for the perfume
      industry. (+)-Ambrein is a major component of ambergris, an intestinal excretion
      of sperm whales that is found only serendipitously. Thus, the demand for (-)
      ambrox is currently mainly met by chemical synthesis. A recent study described
      for the first time the applicability of an enzyme cascade consisting of two
      terpene cyclases, namely squalene-hopene cyclase from Alicyclobacillus
      acidocaldarius (AaSHC D377C) and tetraprenyl-beta-curcumene cyclase from Bacillus
      megaterium (BmeTC) for in vitro (+)-ambrein production starting from squalene.
      Yeasts, such as Pichia pastoris, are natural producers of squalene and have
      already been shown in the past to be excellent hosts for the biosynthesis of
      hydrophobic compounds such as terpenoids. By targeting a central enzyme in the
      sterol biosynthesis pathway, squalene epoxidase Erg1, intracellular squalene
      levels in P. pastoris could be strongly enhanced. Heterologous expression of
      AaSHC D377C and BmeTC and, particularly, development of suitable methods to
      analyze all products of the engineered strain provided conclusive evidence of
      whole-cell (+)-ambrein production. Engineering of BmeTC led to a remarkable one
      enzyme system that was by far superior to the cascade, thereby increasing (+)
      ambrein levels approximately 7-fold in shake flask cultivation. Finally,
      upscaling to 5 L bioreactor yielded more than 100 mg L-1 of (+)-ambrein,
      demonstrating that metabolically engineered yeast P. pastoris represents a
      valuable, whole-cell system for high-level production of (+)-ambrein.

PMID- 30197868
TI  - Development of a new equation in fuzzy logic analysis for ascertaining
      appropriate dose of gamma irradiation of virgin coconut oil.
AB  - Our previous investigation had established 4.2 kGy to be the appropriate dosage
      of gamma irradiation for removal of obnoxious rancid-acid-odor of virgin coconut
      oil (VCO) on the basis of sensory and electronic nose (e nose) studies. This
      study endeavored to revalidate the sensory data employing fuzzy logic analysis.
      An equation has been developed for the first time for deriving defuzzified
      scores, when the sum of the first and third coordinates of the triplet (a b c) of
      overall sensory score was greater than 100, i.e. (a + c) > 100. This study
      reaffirmed 4.2 kGy to be the most preferred dose for deodorization of VCO.
      Besides, ranking of the VCO samples were similar by either approach. *According
      to the fuzzy logic method, overall sensory scores were assigned to the VCO
      samples under investigation, these sensory scores have been represented by a
      triangle and a polygon when (a+c) is less and more than100, respectively.*The
      coordinates of the polygon were determined and a new equation has been developed
      for evaluating defuzzified scores, which has been validated by similarity value
      analysis.*This new methodology of fuzzy logic analysis can be used to rank
      samples rapidly and reliably, without any complexity of conventional similarity
      value approach.

PMID- 30197869
TI  - Methods of determing biokinetics of arsenate accumulation and release in
      Microcystis aeruginosa regulated by common environmental factors: Practical
      implications for enhanced bioremediation.
AB  - Only little information is available on combined effects of abiotic environmental
      factors on algal arsenate (AsV ) metabolic biokinetics. Herein, we demonstrated
      the methods of using the Taguchi statistical method to investigate four
      environmental factors including AsV , nitrate (N), orthophosphate (P) and pH for
      their combined effects on algal growth and arsenic (As) uptake but also
      extracellular adsorption of Microcystis aeruginosa, as well as As release from
      dead algal cells. Results showed that an increase of N facilitated M. aeruginosa
      growth and thus was the principal factor for the algal maximum specific growth
      rate (  MUmax ). P was vital to AsV bioconcentration factor (BCF) and As
      partition coefficients (LogKd ) released from deal algal cells. AsV impacted the
      extracellular As adsorption onto the algal cells, which thereby increased with
      increasing initial AsV level. The initial pH had an imperative effect on the AsV
      uptake (ku ) and release rate (Ke ) from the dead cells. Collectively, the
      condition of low P, high N and alkaline pH level was favorable to As accumulation
      rate of living cells and restrictive to As release rate from dead cells of M.
      aeruginosa. The obtained information can pave a road for extensive understanding
      on efficient utilization of As bioremediation of algae in practical environment.
      *Principal factors were identified on AsV metabolic biokinetics by Taguchi
      method.*High N and pH but low P fasten AsV uptake and reduce As efflux from dead
      cells.*AsV only as the main factor impacted As extracellular adsorption on algal
      cells.

PMID- 30197870
TI  - Novel properties of recombinant Sso7d-Taq DNA polymerase purified using aqueous
      two-phase extraction: Utilities of the enzyme in viral diagnosis.
AB  - Using Sso7d from Sulfolobus solfataricus as the DNA binding protein fused to Taq
      DNA polymerase at its amino terminus, we report the hyper-expression and a novel
      purification methodology of Sso7d-Taq polymerase (S-Taq) using aqueous two-phase
      extraction system followed by Ni-affinity chromatography. The utility of such a
      fusion enzyme in carrying out PCR of human genes from whole blood directly and in
      detecting hepatitis B virus from clinical samples is demonstrated in this
      article. We present data on the enhanced thermo-stability of S-Taq DNA polymerase
      over Taq DNA polymerase and also provide evidence of its higher stability with
      detergents in comparison to Taq polymerase. The purified S-Taq protein showed
      acceptable limits of host genomic DNA levels without the use of DNases and other
      DNA precipitating agents and shows promising potential for use in PCR based
      diagnostics, in-situ PCR's and forensic science.

PMID- 30197872
TI  - Hydrogen peroxide production in a pilot-scale microbial electrolysis cell.
AB  - A pilot-scale dual-chamber microbial electrolysis cell (MEC) equipped with a
      carbon gas-diffusion cathode was evaluated for H2O2 production using acetate
      medium as the electron donor. To assess the effect of cathodic pH on H2O2 yield,
      the MEC was tested with an anion exchange membrane (AEM) and a cation exchange
      membrane (CEM), respectively. The maximum current density reached 0.94-0.96 A/m2
      in the MEC at applied voltage of 0.35-1.9 V, regardless of membranes. The highest
      H2O2 conversion efficiency was only 7.2 +/- 0.09% for the CEM-MEC. This low
      conversion would be due to further H2O2 reduction to H2O on the cathode or H2O2
      decomposition in bulk liquid. This low H2O2 conversion indicates that large-scale
      MECs are not ideal for production of concentrated H2O2 but could be useful for a
      sustainable in-situ oxidation process in wastewater treatment.

PMID- 30197871
TI  - Antimicrobial activity of bacteria isolated from Red Sea marine invertebrates.
AB  - Marine invertebrates-associated microorganisms were considered to be important
      sources of marine bioactive products. This study aims to isolate marine
      invertebrates associated bacteria with antimicrobial activity from the Red Sea
      and test their biosynthetic potential through the detection of PKS and NRPS gene
      clusters involved with the production of bioactive secondary metabolites. In this
      respect, fifty bacterial strains were isolated from eight different Red Sea
      marine invertebrates and screened for their antimicrobial activity against
      standard pathogenic bacteria (Staphylococcus aureus ATCC 25923, Escherichia coli
      ATCC 25922, Bacillus subtilis ATCC 6633) and yeast (Candida albicans ATCC 10231)
      using the standard well diffusion assay. Five isolates showed antifungal activity
      against Candida albicans with no activity recorded against other pathogenic
      bacterial strains. On the other hand when these isolates were screened for the
      presence of biosynthetic gene clusters (PKS and NRPS) by PCR using five sets of
      degenerative primers, 60% of the isolates were shown to contain at least one type
      of PKS and NRPS gene clusters, which indicates the biosynthetic potential of
      these isolates even if the isolates didn't express any biological activity in
      vitro. Moreover the 16S rRNA molecular identification of the isolates reveal the
      biodiversity of the red sea marine invertebrates associated bacteria as they were
      found to belong to several bacterial groups present in Alphaproteobacteria,
      Gammaproteobacteria, Actinobacteria and Firmicutes.

PMID- 30197873
TI  - Chemical characterization and antioxidant properties of exopolysaccharides from
      mangrove filamentous fungi Fusarium equiseti ANP2.
AB  - A filamentous fungi F. equiseti strain ANP2 with good exopolysaccharide (EPS)
      yield, apparent viscosity was screened and isolated from Krishna estuarine
      mangrove sediments. Based on molecular characteristics the selected strain was
      confirmed as F. equiseti, yielded EPS (4.9 +/- 0.25 g/L) and whole cell biomass
      (3.5 +/- 0.2 g/L) in MSM during early stationary phase. The crude EPS was
      purified by chromatography of Q-Sepharose and Superdex-75, affording Ms and MF-1
      fractions were obtained, respectively. Chemical analyses revealed that EPS is
      primarily composed of neutral sugars and proteins. FTIR-spectroscopy revealed
      presence of hydroxyl, carbonyl groups and glycosidic bonds which correspond to
      typical heteropolysaccharide. GC analysis demonstrated that MF-1 mainly consist
      of mannose (72.6%) and glucose (27.3%). Viscosity studies exhibited typical non
      Newtonian pseudoplastic behaviour with high viscosity. The scavenging ability on
      hydroxyl radicals, indicate that MF-1-EPS has good antioxidant activity. Current
      study demonstrated that MF-1 differed from previously characterized Fusarium sp.,
      and can serve as potential antioxidant.

PMID- 30197874
TI  - Genome sequence analysis of Zooshikella ganghwensis strain VG4 and its potential
      for the synthesis of antimicrobial metabolites.
AB  - With antimicrobial resistance on the rise, the discovery of new compounds with
      novel structural scaffolds exhibiting antimicrobial properties has become an
      important area of research. Such compounds can serve as starting points for the
      development of new antimicrobials. In this report, we present the draft genome
      sequence of the Zooshikella ganghwensis strain VG4, isolated from Red Sea
      sediments, that produces metabolites with antimicrobial properties. A genomic
      analysis reveals that it carries at least five gene clusters that have the
      potential to direct biosynthesis of bioactive secondary metabolites such as
      polyketides and nonribosomal peptides. By using in-silico approaches, we predict
      the structure of these metabolites.

PMID- 30197875
TI  - Multifactorial regulators of tumor programmed death-ligand 1 (PD-L1) response.

PMID- 30197876
TI  - New light on the pancreatic cyst conundrum.

PMID- 30197877
TI  - ADAR Mediated RNA Editing Modulates MicroRNA Targeting in Human Breast Cancer.
AB  - RNA editing by RNA specific adenosine deaminase acting on RNA (ADAR) is
      increasingly being found to alter microRNA (miRNA) regulation. Editing of miRNA
      transcripts can affect their processing, as well as which messenger RNAs (mRNAs)
      they target. Further, editing of target mRNAs can also affect their
      complementarity to miRNAs. Notably, ADAR editing is often increased in malignancy
      with the effect of these RNA changes being largely unclear. In addition, numerous
      reports have now identified an array of miRNAs that directly contribute to
      various malignancies although the majority of their targets remain largely
      undefined. Here we propose that modulating the targets of miRNAs via mRNA editing
      is a frequent occurrence in cancer and an underappreciated participant in
      pathology. In order to more accurately characterize the relationship between
      these two regulatory processes, this study examined RNA editing events within
      mRNA sequences of two breast cancer cell lines (MCF-7 and MDA-MB-231) and
      determined whether or not these edits could modulate miRNA associations.
      Computational analyses of RNA-Seq data from these two cell lines identified over
      50,000 recurrent editing sites within human mRNAs, and many of these were located
      in 3' untranslated regions (UTRs). When these locations were screened against the
      list of currently-annotated miRNAs we discovered that editing caused a subset
      (~9%) to have significant alterations to mRNA complementarity. One miRNA in
      particular, miR-140-3p, is known to be misexpressed in many breast cancers, and
      we found that mRNA editing allowed this miRNA to directly target the apoptosis
      inducing gene DFFA in MCF-7, but not in MDA-MB-231 cells. As these two cell lines
      are known to have distinct characteristics in terms of morphology, invasiveness
      and physiological responses, we hypothesized that the differential RNA editing of
      DFFA in these two cell lines could contribute to their phenotypic differences.
      Indeed, we confirmed through western blotting that inhibiting miR-140-3p
      increases expression of the DFFA protein product in MCF-7, but not MDA-MB-231,
      and further that inhibition of miR-140-3p also increases cellular growth in MCF
      7, but not MDA-MB-231. Broadly, these results suggest that the creation of miRNA
      targets may be an underappreciated function of ADAR and may help further
      elucidate the role of RNA editing in tumor pathogenicity.

PMID- 30197879
TI  - Influence of Micropatterned Grill Lines on Entamoeba histolytica Trophozoites
      Morphology and Migration.
AB  - Entamoeba histolytica, the causal agent of human amoebiasis, has two
      morphologically different phases: a resistant cyst and a trophozoite responsible
      for the invasion of the host tissues such as the colonic mucosa and the
      intestinal epithelium. During in vitro migration, trophozoites usually produce
      protuberances such as pseudopods and rarely filopodia, structures that have been
      observed in the interaction of trophozoites with human colonic epithelial tissue.
      To study the different membrane projections produced by the trophozoites,
      including pseudopods, filopodia, uropods, blebs, and others, we designed an
      induction system using erythrocyte extract or fibronectin (FN) in micropatterned
      grill lines (each micro-line containing multiple micro-portions of FN or
      erythrocyte extract) on which the trophozoites were placed in culture for
      migration assays. Using light, confocal, and scanning electron microscopy, we
      established that E. histolytica trophozoites frequently produce short and long
      filopodia, large retractile uropods in the rear, pseudopods, blebs, and others
      structures, also showing continuous migration periods. The present study provides
      a simple migration method to induce trophozoites to generate abundant membrane
      protrusion structures that are rarely obtained in normal or induced cultures,
      such as long filopodia; this method will allow a-better understanding of the
      interactions of trophozoites with FN and cell debris. E. histolytica trophozoites
      motility plays an important role in invasive amoebiasis. It has been proposed
      that both physical forces and chemical signals are involved in the trophozoite
      motility and migration. However, the in vivo molecules that drive the chemotactic
      migration remain to be determined. We propose the present assay to study host
      molecules that guide chemotactic behavior because the method is highly
      reproducible, and a live image of cell movement and migration can be quantified.

PMID- 30197880
TI  - In silico Description of LAT1 Transport Mechanism at an Atomistic Level.
AB  - The molecular mechanism of transport mediated by LAT1, a sodium-independent
      antiporter of large neutral amino acids, was investigated through in silico
      procedures, specifically making reference to two transported substrates, tyrosine
      (Tyr) and leucine methyl ester (LME), and to 3,5-diiodo-L-tyrosine (DIT), a well
      known LAT1 inhibitor. Two models of the transporter were built by comparative
      modeling, with LAT1 either in an outward-facing (OF) or in an inward-facing (IF)
      conformation, based, respectively, on the crystal structure of AdiC and of GadC.
      As frequently classic Molecular Dynamics (MD) fails to monitor large-scale
      conformational transitions within a reasonable simulated time, the OF structure
      was equilibrated for 150 ns then processed through targeted MD (tMD). During this
      procedure, an elastic force pulled the OF structure to the IF structure and
      induced, at the same time, substrates/inhibitor to move through the transport
      channel. This elastic force was modulated by a spring constant (k) value; by
      decreasing its value from 100 to 70, it was possible to comparatively account for
      the propensity for transport of the three tested molecules. In line with our
      expectations, during the tMD simulations, Tyr and LME behaved as substrates,
      moving down the transport channel, or most of it, for all k values. On the
      contrary, DIT behaved as an inhibitor, being (almost) transported across the
      channel only at the highest k value (100). During their transit through the
      channel, Tyr and LME interacted with specific amino acids (first with Phe252 then
      with Thr345, Arg348, Tyr259, and Phe262); this suggests that a primary as well as
      a putative secondary gate may contribute to the transport of substrates. Quite on
      the opposite, DIT appeared to establish only transient interactions with side
      chains lining the external part of the transport channel. Our tMD simulations
      could thus efficiently discriminate between two transported substrates and one
      inhibitor, and therefore can be proposed as a benchmark for developing novel LAT1
      inhibitors of pharmacological interest.

PMID- 30197881
TI  - Comprehensive Study of the Enzymatic Catalysis of the Electrochemical Oxygen
      Reduction Reaction (ORR) by Immobilized Copper Efflux Oxidase (CueO) From
      Escherichia coli.
AB  - In recent years, enzymatic fuel cells have experienced a great development
      promoted by the availability of novel biological techniques that allow the access
      to a large number of enzymatic catalysts. One of the most important aspects in
      this area is the development of biocatalysts for the oxygen reduction reaction
      (ORR). Laccases from the group of enzymes called blue multi-cooper oxidases have
      received considerable attention because of their ability to catalyze the
      electrochemical oxygen reduction reaction to water when immobilized on metallic
      or carbonaceous electrode materials. In this paper we report a comprehensive
      study of the electrocatalytic activity of the enzyme Copper efflux oxidase (CueO)
      from Escherichia coli immobilized on different electrode materials. The influence
      of the electrode substrate employed for protein immobilization was evaluated
      using glassy carbon, gold or platinum electrodes. Gold and platinum electrodes
      were modified using different self-assembled monolayers (SAM) able to tune the
      electrostatic interaction between the protein and the substrate, depending on the
      nature of the terminal functional group in the SAM. The effects of protein
      immobilization time, electrode potential, solution pH and temperature, protein
      and O2 concentration have been carefully investigated. Finally, direct electron
      transfer (DET) was investigated in the presence of the following inhibitors:
      fluoride (F-), chloride (Cl-) and azide ( N3- ).

PMID- 30197882
TI  - Exploring the Reasons for Decrease in Binding Affinity of HIV-2 Against HIV-1
      Protease Complex Using Interaction Entropy Under Polarized Force Field.
AB  - In this study, the differences of binding patterns between two type HIV (HIV-1
      and HIV-2) protease and two inhibitors (darunavir and amprenavir) are analyzed
      and compared using the newly developed interaction entropy (IE) method for the
      entropy change calculation combined with the polarized force field. The
      functional role of protonation states in the two HIV-2 complexes is investigated
      and our study finds that the protonated OD1 atom of Asp25' in B chain is the
      optimal choice. Those calculated binding free energies obtained from the
      polarized force field combined with IE method are significantly consistent with
      the experimental observed. The bridging water W301 is favorable to the binding of
      HIV-1 complexes; however, it is unfavorable to the HIV-2 complexes in current
      study. The volume of pocket, B-factor of Calpha atoms and the distance of flap
      tip in HIV-2 complexes are smaller than that of HIV-1 consistently. These changes
      may cause localized rearrangement of residues lining their surface and finally
      result in the different binding mode for the two types HIV. Predicated hot-spot
      residues (Ala28/Ala28', Ile50/Ile50', and Ile84/Ile84') are nearly same in the
      four systems. However, the contribution to the free energy of Asp30 residue is
      more favorable in HIV-1 system than in HIV-2 system. Current study, to some
      extent, reveals the origin for the decrease in binding affinity of inhibitors
      against HIV-2 compared with HIV-1 and will provides theoretical guidance for
      future design of potent dual inhibitors targeting two type HIV protease.

PMID- 30197878
TI  - Metabolic Plasticity of Tumor Cell Mitochondria.
AB  - Mitochondria are dynamic organelles that exchange a multiplicity of signals with
      other cell compartments, in order to finely adjust key biological routines to the
      fluctuating metabolic needs of the cell. During neoplastic transformation, cells
      must provide an adequate supply of the anabolic building blocks required to meet
      a relentless proliferation pressure. This can occur in conditions of inconstant
      blood perfusion leading to variations in oxygen and nutrient levels. Mitochondria
      afford the bioenergetic plasticity that allows tumor cells to adapt and thrive in
      this ever changing and often unfavorable environment. Here we analyse how
      mitochondria orchestrate the profound metabolic rewiring required for neoplastic
      growth.

PMID- 30197883
TI  - Shadow Cell Differentiation: A Comparative Analysis of Modes of Cell Death with
      Apoptosis and Epidermal/Trichilemmal Keratinization.
AB  - Shadow cells are characterized by an eosinophilic cytoplasm and a ghost-like
      nuclear contour; the cell shape is preserved, in spite of nuclear disappearance.
      Shadow cell nests (SCNs) are frequently observed in pilomatricoma (PMX), where
      the transitional cells immediately adjacent to SCNs often have a crescent-shaped
      nucleus showing fragmentation similar to that of apoptotic bodies. They show
      nuclear accumulation of beta-catenin and DNA double strand breaks (as revealed by
      in situ 3'-tailing reaction or immunohistochemistry for single-stranded DNA
      [ssDNA]), while they are negative for cleaved caspase-3 or cleaved lamin A,
      suggesting that shadow cell differentiation (SCD) is a caspase-independent
      programmed cell death. SCD can be differentiated from epidermal keratinization
      (EK) and trichilemmal keratinization (TK) based on the expression pattern of beta
      catenin, ssDNA, and caspase-14/CD138. SCD is observed not only in PMX, but also
      sometimes in basal cell carcinomas, gonadal teratomas, and various extra
      cutaneous carcinomas. In particular, SCNs are found in 24$ of endometrial
      adenoacanthoma and are derived from squamoid morules. This establishes a link
      between basaloid cells in PMX and squamoid morules in endometrial adenoacanthomas
      as common precursors of shadow cells. Overall, it is suggested that SCD is
      different from, but partly similar to, apoptosis and that SCD and EK/TK should be
      differentiated from the standpoint of cell death/differentiation.

PMID- 30197884
TI  - Melanocytic Lesions of the Nail Unit.
AB  - Melanocytic lesions of the nail unit are traditionally classified as follows:
      melanocytic activation, lentigo, nevi, and melanoma. Undoubtedly, melanoma is the
      most important malignant tumor of the nail unit. Differentiating nail unit
      melanoma from other melanocytic lesions is often difficult both clinically and
      histopathologically. This article will first describe the histology of the nail
      unit, followed by a brief summary of clinical and histopathological features as
      well as differential diagnosis of melanocytic lesions of the nail unit.

PMID- 30197886
TI  - Atrichia with Papular Lesions: Importance of Histology at an Early Disease Stage.
AB  - We report the case of a 5-year-old girl born from consanguineous parents,
      presenting with alopecia universalis since the age of 8 months, without papules
      or cysts over the scalp or body. The goal of this paper is to emphasize the
      relevance of histopathology for the early diagnosis of atrichia with papular
      lesions in children with alopecia universalis, in settings where genetic testing
      may not be available.

PMID- 30197885
TI  - Activation of the Calcium-Sensing Receptor Corrects the Impaired Mitochondrial
      Energy Status Observed in Renal Polycystin-1 Knockdown Cells Modeling Autosomal
      Dominant Polycystic Kidney Disease.
AB  - Autosomal Dominant Polycistic kidney Disease (ADPKD) is a renal channelopathy due
      to loss-of-function mutations in the PKD1 or PKD2 genes, encoding polycystin-1
      (PC1) or polycystin-2 (PC2), respectively. PC1 is a large protein found
      predominantly on the plasma membrane where interacts with different proteins,
      including PC2. PC2 is a smaller integral membrane protein also expressed in
      intracellular organelles, acting as a non-selective cation channel permeable to
      calcium. Both PC1 and PC2 are also localized to the primary cilium of renal
      epithelial cells serving as mechanosensor that controls calcium influx through
      the plasma membrane and regulates intracellular calcium release from the
      endoplasmic reticulum. The mechanisms by which PC1/2 dysfunction leads to ADPKD
      needs still to be clarified. We have recently reported that selective Calcium
      Sensing Receptor (CaSR) activation in human conditionally immortalized Proximal
      Tubular Epithelial cells deficient for PC1 (ciPTEC-PC1KD), deriving from urine
      sediments reduces intracellular cAMP and mTOR activity, and increases
      intracellular calcium reversing the principal ADPKD dysregulations. Reduced
      cellular free calcium found in ADPKD can, on the other hand, affect mitochondrial
      function and ATP production and, interestingly, a relationship between
      mitochondria and renal polycystic diseases have been suggested. By using ciPTEC
      PC1KD as experimental tool modeling of ADPKD, we show here that, compared with
      wild type cells, ciPTEC-PC1KD have significantly lower mitochondrial calcium
      levels associated with a severe deficit in mitochondrial ATP production,
      secondary to a multilevel impairment of oxidative phosphorylation. Notably,
      selective CaSR activation with the calcimimetic NPS-R568 increases mitochondrial
      calcium content close to the levels found in resting wild type cells, and fully
      recovers the cell energy deficit associated to the PC1 channel disruption.
      Treatment of ciPTEC-PC1KD with 2-APB, an IP3R inhibitor, prevented the rescue of
      bioenergetics deficit induced by CaSR activation supporting a critical role of
      IP3Rs in driving ER-to-mitochondria Ca2+ shuttle. Together these data indicate
      that, besides reversing the principal dysregulations considered the most proximal
      events in ADPKD pathogenesis, selective CaSR activation in PKD1 deficient cells
      restores altered mitochondrial function that, in ADPKD, is known to facilitate
      cyst formation. These findings identify CaSR as a potential therapeutic target.

PMID- 30197887
TI  - Health-Related Quality of Life of Patients with Hidradenitis Suppurativa Measured
      with the 15D Instrument and Comparison with the General Population and Patients
      with Psoriasis.
AB  - Background: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease
      significantly impacting health-related quality of life (HRQoL). We measured the
      HRQoL of Finnish HS patients and compared it with that of the general population
      and psoriasis patients. Methods: Twenty-six diagnosed HS patients completed the
      15D HRQoL questionnaire (15D), the Dermatology Life Quality Index (DLQI), and the
      Beck Depression Inventory-21 (BDI-21). The correlation between the results of
      these instruments was analyzed and the 15D results were compared with an age
      standardized general population and psoriasis patients. Results: Compared with an
      age-standardized general population, HS patients scored statistically
      significantly worse on several 15D dimensions. A statistically significant
      difference compared to psoriasis patients was detected on the sexual activity
      dimension. Even though not statistically significant, the observed mean values of
      the remaining dimensions suggest that clinically important differences may exist.
      The 15D score negatively correlated with the DLQI score (r = -0.492; p = 0.011)
      and the BDI-21 score (r = -0.592; p = 0.001). Conclusions: HS is a serious
      condition, with an impact at least comparable to that of psoriasis. This study
      shows that the 15D is a feasible tool for examining HRQoL in HS patients.

PMID- 30197888
TI  - Antibiofilm Treatment for Onychomycosis and Chronic Fungal Infections.
AB  - Onychomycosis is a difficult-to-treat chronic fungal infection of the nail. The
      chronic nature of onychomycosis, with relevance to current treatment practices,
      could be attributed to host anergy, development of increased virulence in causal
      agents (multidrug resistance efflux pump), and biofilms. Biofilms must be
      disrupted prior to antifungal treatment suggesting the necessity of combination
      treatment. Once the biofilm has been disrupted, further techniques in addition to
      antifungal usage are suggested to ensure a positive prognosis including use of
      antimicrobial photodynamic therapy or low-frequency surface acoustic waves.
      Overall, with continued success in developing antibiofilm treatment for bacterial
      and yeast pathogens, therapy can be more quickly expanded to dermatophytes. With
      a rise in predisposing factors, it is important to preemptively address treatment
      for this disease with continued investigation into antibiofilm therapy including
      optimal treatment combinations and dosages targeted specifically at
      dermatophytes.

PMID- 30197889
TI  - Variability in Systemic Treatment Efficacy for Onychomycosis: Information That
      Clinical Studies Do Not Impart to the Office Dermatologist.
AB  - Wide differences in the cure rates of onychomycosis in various clinical studies
      can be avoided if we bear in mind some insights that will help us make study
      results more consistent. We suggest less rigid criteria in defining the cure
      rate, the inclusion of all toenails in studies, and the exclusion of nails with a
      history of trauma. Rather than address patients as a homogenous group, regardless
      of age, we suggest dividing them into age groups. Researchers should not forget
      inflammatory diseases that can imply changes on the nails and should take into
      account the duration of onychomycosis, nail changes caused by asymmetry, and the
      possibility of dermatophytoma.

PMID- 30197890
TI  - Facial Papules in Frontal Fibrosing Alopecia: Beyond Vellus Hair Follicle
      Involvement.
AB  - Background: Frontal fibrosing alopecia (FFA) is considered a variant of lichen
      planopilaris affecting mainly the frontotemporal hairline. Since the first report
      in 1994, several other clinical features have been associated with the disease,
      such as facial papules (FP). Even though FP have been linked to facial vellus
      hair follicle involvement, how this finding alone could lead to the formation of
      clinically evident FP in FFA patients had not yet been addressed. Objective: To
      describe histopathological findings of FP in the context of FFA and to highlight
      features that may be linked to their clinical formation. Methods: Cutaneous FP
      biopsies of FFA patients performed between January 2016 and May 2017 were
      retrieved from our pathology database and reexamined by 2 pathologists. Results:
      Histological sections of thirteen 3.0-mm punch biopsy specimens (2 horizontally
      and 11 vertically oriented) were collected from 7 patients. Eleven specimens
      demonstrated prominent sebaceous glands and 10 dilated sebaceous ducts. Pinkus
      acid orcein staining revealed reduction and fragmentation of the elastic fibers
      in 12 samples and, in 7 of these, this finding was observed in both the papillary
      and reticular dermis, particularly around sebaceous lobules. Vellus hair follicle
      involvement was only seen in 2 samples. Conclusions: Prominent sebaceous lobules
      with dilated ducts associated with an abnormal elastic framework seem to be the
      main explanation for the formation of FP in the context of FFA.

PMID- 30197891
TI  - Meeting Report on the 1st Singapore Nail Workshop and Cadaveric Nail Surgery
      Course 2017.

PMID- 30197892
TI  - Subungual Solitary Angiokeratoma Simulating a Squamous Cell Carcinoma.
AB  - Subungual angiokeratoma is extremely rare. Only 1 case is reported in the
      literature, presenting as a longitudinal pigmented band on a toenail. We report a
      case of a subungual angiokeratoma on a fingernail of a 43-year-old woman,
      clinically mimicking a squamous cell carcinoma. Medical imaging revealed a soft
      tissue tumor and erosion of the distal phalanx. Although extremely rare, solitary
      angiokeratomas may arise in the nail apparatus and should be added to the
      differential diagnosis of subungual warty tumors.

PMID- 30197893
TI  - Nail Sarcoidosis Presenting with Longitudinal Erythronychia.
AB  - A 37-year-old woman presented with progressive longitudinal erythronychia and
      onychorrhexis of the toenails. She had a history of sarcoidosis of the lung and
      nose, which was silent without treatment at the time of presentation.
      Histopathological examination of a nail matrix biopsy revealed granulomas with
      palisading histiocytes in the connective tissue and a lymphocytic infiltrate in
      and around the granulomas without necrosis. Based on the clinical presentation,
      medical history, and histopathological examination, the diagnosis of nail
      sarcoidosis was made. Treatment with triamcinolone acetonide 40 mg/mL resulted in
      the disappearance of the onychorrhexis and a significant improvement of
      erythronychia. To our knowledge, a clinical presentation with longitudinal
      erythronychia as seen in our patient has not been previously described. Bone
      involvement of the underlying distal phalanges and systemic involvement can be
      paucisymptomatic but are present in most patients with sarcoidosis of the nails.
      Nail and bone involvement are both regarded as features of chronic and systemic
      sarcoidosis. Screening for bone and systemic involvement should be performed in
      all patients with nail sarcoidosis, as this may influence decisions on treatment
      and follow-up. Therefore, it is important to recognize longitudinal erythronychia
      as a possible clinical sign of nail sarcoidosis.

PMID- 30197894
TI  - Efficacy and Safety of a Topical Botanical in Female Androgenetic Alopecia: A
      Randomized, Single-Blinded, Vehicle-Controlled Study.
AB  - Introduction: Androgenetic alopecia (AGA) in females is a difficult to treat skin
      disorder. A novel topical botanical lotion has been approved for its treatment.
      It acts by increasing Bcl-2, perifollicular Langerhans and mast cells, and
      perifollicular collagen. The aim of this study was to evaluate the efficacy and
      safety of this lotion in females. Methods: Forty women with AGA were randomized
      to apply the active lotion or placebo, twice daily for 24 weeks. Subjects were
      evaluated at 0, 12, and 24 weeks by clinical examination, photographic
      documentation, quality of life evaluation (DLQI), and trichogram (anagen to
      telogen ratio). Results: The clinical evaluation demonstrated an increased hair
      density in the intervention group (great improvement in 7.7$, moderate in 88.5$,
      and stable in 3.8$). The self-assessment score increased from 4.5 to 6.0 (24
      weeks), and the DLQI improved from 4 to 3 in the intervention group (p < 0.001).
      The mean anagen to telogen ratio in the intervention group was 2.1, 3.9, and 6.0
      at 0, 12, and 24 weeks, respectively, whereas in the control group it was 2.2,
      3.8, and 3.3, respectively. Conclusion: The new topical botanical lotion showed
      remarkable efficacy, with a high degree of patient satisfaction and improvement
      of their quality of life.

PMID- 30197895
TI  - A Retrospective Study Comparing K101 Nail Solution as a Monotherapy and in
      Combination with Oral Terbinafine or Itraconazole for the Treatment of Toenail
      Onychomycosis.
AB  - Background: Onychomycosis is a difficult-to-treat fungal infection of the nails.
      The efficacy of monotherapy is not ideal, and combination therapies provide an
      alternative that may increase treatment efficacy. Method: A retrospective
      analysis of data from 91 patients was undertaken. Treatment for toenail
      onychomycosis occurred between 2014 and 2016 and consisted of combination therapy
      with oral terbinafine (250 mg/day for 12 weeks) or itraconazole (3 pulses, 400
      mg/day for 7 days) + K101 nail solution daily, or K101 nail solution monotherapy.
      Efficacy outcomes at 12 and 15 months were analyzed. Results: At 12 months, the
      clinical cure rate for combination of terbinafine + K101 solution was
      significantly higher than that for K101 monotherapy (p = 0.008). Patients
      receiving this combination also showed significant improvement in percent of
      affected nail at 3 months (p = 0.029), while patients receiving itraconazole +
      K101 solution demonstrated improvement in percent of affected nail at 6 months (p
      = 0.037). At 15 months, there was no significant difference between treatments
      for complete, clinical, and mycological cure. Conclusion: Combination therapy
      with oral terbinafine or itraconazole and K101 nail solution results in clearance
      of infected nail earlier than that with topical K101 alone. These combinations
      may encourage compliance and be effective for patients with moderate
      onychomycosis.

PMID- 30197896
TI  - Onychomatricoma: A Rare Nail Tumor with an Unusual Clinical Presentation.
AB  - First described in 1992, onychomatricoma is a rare, benign, fibroepithelial tumor
      of the nail matrix with few reported cases in the literature. The tumor
      predominately affects the fingers of Caucasian women during the 5th decade of
      life and is typically slow growing and painless. The authors present a unique
      clinical presentation of a giant onychomatricoma in a darker-skinned 60-year-old
      South Asian individual who presented with a large dome-shaped nail that was
      smooth, shiny, and green.

PMID- 30197897
TI  - Ingrown Hairs: A Recurrent Trichoscopic Feature in Scarring Alopecias.

PMID- 30197898
TI  - Seasonal Onychomadesis of the Great Toes.
AB  - Onychomadesis occurs when the proximal nail plate becomes unattached to the
      underlying structures. When only one or a few nails are involved, the cause is
      usually physical trauma. A 23-year-old female presented with a 4-year history of
      recurrent onychomadesis involving her bilateral great toes that occurred during
      the springtime. While recurrent trauma from winter shoes or athletic activities
      may be a contributing factor, our patient was convinced that wearing tight
      fitting socks during winter nights was the primary pathophysiologic process. By
      wearing socks only during the days and decreasing the amount of time the nails
      spent traumatized due to pressure, the patient's recurrent condition was
      eliminated.

PMID- 30197899
TI  - Erosive Pustular Dermatosis: A Manifestation of Immunosenescence A Report of 8
      Cases.
AB  - Erosive pustular dermatosis (EPD) is a rare condition of the scalp and legs that
      is marked by crusted erosions or superficial ulcerations that may result in
      scarring alopecia and chronic wounds. The condition predominantly affects elderly
      female as compared to male patients. Its pathogenesis remains poorly understood.
      The majority of the cases in the literature are from the United Kingdom and
      continental Europe. In this series, we present 8 North American patients with EPD
      of the scalp, one of whom also had involvement of the legs and another with the
      involvement of the face. All our patients were advanced in age and had a
      predisposition to chronic actinic damage, which are common characteristics of EPD
      previously reported in the literature. We hypothesize that immunosenescence leads
      to an aberrant immune response to wound healing and, along with other factors
      such as a loss of the normal epidermal barrier, ultraviolet damage, and hormonal
      factors, may contribute to the development of this condition.

PMID- 30197900
TI  - Scalp Itch: A Systematic Review.
AB  - Scalp itch is a frequent complaint in the dermatological setting. It is common
      for the dermatologist to encounter patients with no evident cause of scalp
      pruritus, making it a distressing situation for both the clinician and the
      patient. The aim of this paper is to propose a systematic approach to scalp itch,
      which classifies scalp pruritus into two types: (1) with or (2) without
      dermatological lesions, and presence or absence of hair loss. Also, it is
      important to think first about the most common causes and then rule out other,
      less common etiologies. The acronym SCALLP and the five steps for scalp
      evaluation (listen, look, touch, magnify, and sample) are useful tools to keep in
      mind for an assertive approach in these patients.

PMID- 30197901
TI  - Acute Kidney Failure as a Single Complication of Varicella Virus Infection in an
      Adult Patient.
AB  - Background: Varicella zoster virus (VZV) is distributed worldwide and is highly
      contagious. In adults and immunosuppressed patients of any age, the clinical
      course is much more severe. The most severe complications are pneumonia (the main
      cause of lethal outcomes in this infection), encephalitis, and very rarely Reye
      syndrome and hepatitis. Case Presentation: We present a 59-year-old man who came
      to the emergency department due to varicella and diarrhea. During initial
      evaluation acute kidney failure (AKF) was diagnosed, and the patient was admitted
      to the intensive care unit. Continuous renal replacement therapy was applied, and
      the patient was treated with acyclovir in adjusted doses; renal biopsy revealed
      acute tubular necrosis. Complete renal function recovery was established after 12
      days. Conclusion: VZV infection occurs in a range of clinical scenarios,
      sometimes presenting only with mild symptoms, but in some other setting it can
      result in severe AKF even in healthy kidneys. Acute VZV infection can lead to
      isolated, clinically significant kidney failure. The administration of continuous
      renal replacement therapy and adjusted doses of acyclovir has a favorable effect
      on the course of the infection, with complete recovery of kidney function.

PMID- 30197902
TI  - A Rare Case of Severe Metabolic Alkalosis with Unusual Hyperproteinemia Treated
      with Continuous Renal Replacement Therapy and Regional Citrate Anticoagulation.
AB  - A 23-year-old woman was referred to the tertiary centre with acute kidney injury
      and severe metabolic alkalosis following an accidental ethylene glycol poisoning.
      The patient had been treated with continuous haemodiafiltration and regional
      citrate anticoagulation, and a tracheostomy was performed due to pneumonia.
      Besides severe metabolic alkalosis and hypernatremia, the laboratory tests
      revealed total protein of 108 g/L on admission to the tertiary centre. The
      haemodiafiltration with regional citrate anticoagulation continued with parallel
      correction of the alkalosis and normalisation of the total plasma protein. The
      tracheostomy was decannulated and the patient was discharged to the district
      hospital. The case demonstrates the usefulness of regional citrate
      anticoagulation even in severe metabolic alkalosis which was likely related to
      the method setting prior to admission and to an overcompensation of the initial
      severe metabolic acidosis. The unusual hyperproteinaemia might be interpreted
      with the aid of the Stewart-Fencl model of the acid-base regulation.

PMID- 30197903
TI  - A Case of Chronic Calcium Oxalate Nephropathy due to Short Bowel Syndrome and
      Cholecystectomy.
AB  - Background: Oxalate nephropathy is a rare disease. Especially chronic oxalate
      nephropathy still has many unknown aspects as compared to acute oxalate
      nephropathy with relatively well-known causality. Case Presentation: The patient
      was a 70-year-old woman who had a history of small bowel resection 25 years
      before, cholecystectomy 10 years before, and renal stones (calcium oxalate
      stones) 7 years before. She had been suffering from chronic diarrhea and had been
      treated by a local physician. The patient was found to have renal dysfunction
      (creatinine 3.09 mg/dL, eGFR 12.3 mL/min/1.73 m2, hemoglobin 7.8 g/dL) and was
      referred to our department. The patient was admitted to our hospital for further
      investigation. Renal ultrasound showed hepatorenal echo contrast in an opposite
      manner and clear contrast between the renal cortex and medullary pyramid. Renal
      biopsy was performed, and histological examination showed tubulointerstitial
      disorder due to deposition of calcium oxalate. Daily urinary excretion of calcium
      oxalate was significantly increased. The patient was encouraged to drink water
      and administered vitamin B6, citric acid, K and Na hydrate. Thereafter, her
      symptoms improved. Conclusion: Case reports of chronic oxalate neuropathy are
      rare in the literature, and its underlying mechanism has not been understood. Our
      patient had a history of small bowel resection and cholecystectomy. We considered
      that her short bowel syndrome had influenced the development of calcium oxalate
      nephropathy.

PMID- 30197904
TI  - Disseminated Strongyloidiasis in Association with Nephrotic Syndrome.
AB  - Strongyloidiasis is a well-known parasitic infection endemic in tropical and
      subtropical areas of the world. While most infected individuals are asymptomatic,
      strongyloidiasis-related glomerulopathy has not been well documented. We present
      a case of disseminated strongyloidiasis in a patient with minimal change
      nephrotic syndrome treated with high-dose corticosteroids. The remission of
      nephrotic syndrome after treatment of strongyloidiasis suggests a possible causal
      relationship between Strongyloides and nephrotic syndrome.

PMID- 30197906
TI  - Acute Kidney Injury after Pembrolizumab-Induced Adrenalitis and Adrenal
      Insufficiency.
AB  - Pembrolizumab is an immune checkpoint inhibitor that targets the programmed cell
      death protein 1 (PD-1) antigen and induces an immune response against tumor
      tissues. It has been successful in inducing remission in patients with severe
      metastatic disease, often refractory to other chemotherapeutic agents. The risk
      of injury of other organ systems has been noted with reported cases of glomerular
      disease and endocrine disease. In addition, hypophysitis as well as
      dermatological and gastroenterological side effects have been reported. Renal
      injury with immune checkpoint inhibitors like nivolumab and pembrolizumab is
      usually mediated via interstitial nephritis, though glomerular disease
      presentations like anti-neutrophil cytoplasmic antibody-associated vasculitis,
      immune complex disease, and thrombotic microangiopathy have also been reported.
      We report a 70-year-old Caucasian male who underwent treatment with pembrolizumab
      for adenocarcinoma of the lung. He developed acute adrenal insufficiency and
      concomitant severe hypotension upon presentation. He did not require renal
      replacement therapy, rather his severe acute kidney injury resolved with
      hydration, normalization of blood pressures with vasopressors, and treatment with
      high-dose corticosteroids. His urinary indices (fractional excretion of urea,
      FEUrea) and clinical course were highly suspicious for acute tubular necrosis
      that resolved quickly after treating his underlying adrenalitis. The urinary
      sediment, proteinuria, and clinical course were not typical for the usually
      expected renal lesion of interstitial nephritis in patients treated with immune
      checkpoint inhibitors.

PMID- 30197905
TI  - Case Report: Patient with Hepatitis C, p-ANCA, and Cryoglobulin Antibodies
      Presenting with Necrotizing Crescentic p-ANCA Glomerulonephritis.
AB  - Hepatitis C (HCV) infection has a prevalence of 3 million infected individuals in
      the United States, according to recent Center for Disease Control reports, and
      can have various renal manifestations. Cryoglobulins, antibodies that precipitate
      at colder temperatures in vitro, are a relatively common cause of renal disease
      in HCV infection. The cryoglobulin proteins can form occlusive aggregates in
      small glomerular capillary lumina or deposit in other areas of the glomerulus,
      resulting in hypocomplementemia, proteinuria, hematuria, and renal injury. The
      typical biopsy pattern is that of membranoproliferative glomerulonephritis
      (MPGN). There are, however, other HCV-related patterns of glomerular injury. Anti
      neutrophil cytoplasmic antibodies (ANCA) are known to exist in HCV-infected
      patients. In many reported cases, ANCA serologic testing may appear positive due
      to cross-reactivity of the immune assays; however, the biopsy findings do not
      support ANCA-associated crescentic glomerulonephritis (GN)/vasculitis as the
      primary cause of glomerular injury. There are rare reports of microscopic
      polyangiitis (MPA) p-ANCA vasculitis, in patients with HCV infection. In
      comparison with the MPGN pattern of cryoglobulinemic glomerular injury, biopsies
      from these HCV-infected patients with concomitant MPA revealed a crescentic GN,
      associated with normal serum complement levels. We present a case of HCV
      associated glomerular disease with the surprising biopsy finding of necrotizing
      and crescentic p-ANCA GN, with a background, low-grade mesangial immune complex
      GN. Thus, p-ANCA disease should also be considered in HCV-infected patients, in
      addition to the more typical lesions of MPGN or cryoglobulinemic GN.

PMID- 30197907
TI  - Artificial T Cell Mimetics to Combat Melanoma Tumor Growth.
AB  - Despite recent breakthroughs in melanoma treatment with anti-PD-1 immunotherapy,
      innovative approaches are needed to improve off-target effects. In this study, we
      report a T cell mimetic microparticle delivery of soluble PD1 aiming at providing
      a carrier substrate for future combinatorial and targeting efforts.
      Microparticles of sizes varying from (5 MUm to-7 MUm) were conjugated with
      soluble mouse or human PD-1 through nearly irreversible binding between
      streptavidin and biotin. PD-1 conjugated microparticles (PDMPs) suppressed 3
      dimensional tumor growth of human A375 and mouse B16-F10 melanoma cells compared
      to control microparticles conjugated with the Fc portion of human IgG1 (IgG1MPs).
      This can be attributed to competitive inhibition by PDMPs on a melanoma cell
      intrinsic PD-1/PD-L1 pathway. A single, local administration of mPDMPs in a B16
      F10 mouse melanoma model inhibited tumor growth significantly compared to control
      IgMPs at the same dose. CD45+ immune cells were found to infiltrate tumors
      treated with mPDMPs as a mechanism for tumor control. These results collectively
      suggest that PDMPs can target the melanoma cell-intrinsic PD-1/PD-L1 pathway and
      that these artificial T cell mimetics can be the scaffold for further
      improvements in anti-tumor immunotherapy.

PMID- 30197909
TI  - Enzymatic synthesis of geranyl acetate in packed bed reactor in supercritical
      carbon dioxide under various pressure-temperature conditions and reactor
      configurations.
AB  - Data in this paper describes the catalytic performances, expressed in terms of
      conversion %, of geraniol and acetic acid to geranyl acetate, using the
      immobilized lipase B from Candida antarctica in packed bed reactors (PBR) using
      supercritical CO2 as a solvent. Readers will find data related to different
      Figures or equations of the article as well as supplementary data that will help
      to make the difference between flowrates of CO2 in a liquid state and
      corresponding flowrates of supercritical CO2 for various CO2 pressure and
      temperature combinations.

PMID- 30197910
TI  - Dataset for the estimation of costs for direct contact condenser.
AB  - The dataset on equations and procedures for the estimation of detailed capital
      and annual costs for direct contact condenser are presented. Full dataset on four
      design cases relevant to the comparisons on the costs of air and oxy-fuel direct
      contact condenser is given. The data are presented in this format to allow the
      comparison with those from other researchers in this field. The data presented
      are related to the article entitled "A comparative study on the design of direct
      contact condenser for air and oxy-fuel combustion flue gas based on Callide Oxy
      fuel Project" (Liu et al., 2018) [1].

PMID- 30197908
TI  - Hypothesis Testing and Statistical Analysis of Microbiome.
AB  - After the initiation of Human Microbiome Project in 2008, various biostatistic
      and bioinformatic tools for data analysis and computational methods have been
      developed and applied to microbiome studies. In this review and perspective, we
      discuss the research and statistical hypotheses in gut microbiome studies,
      focusing on mechanistic concepts that underlie the complex relationships among
      host, microbiome, and environment. We review the current available statistic
      tools and highlight recent progress of newly developed statistical methods and
      models. Given the current challenges and limitations in biostatistic approaches
      and tools, we discuss the future direction in developing statistical methods and
      models for the microbiome studies.

PMID- 30197911
TI  - Data on degradome sequencing and analysis from mock-inoculated and Fusarium
      oxysporum treated leaves samples in Persicaria minor.
AB  - Degradome sequencing referred as parallel analysis of RNA ends (PARE) by
      modifying 5'-rapid amplification of cDNA ends (RACE) with deep sequencing method.
      Deep sequencing of 5' products allow the determination of cleavage sites through
      the mapping of degradome fragments against small RNAs (miRNA or siRNA) on a large
      scale. Here, we carried out degradome sequencing in medicinal plant, Persicaria
      minor, to identify cleavage sites in small RNA libraries in control (mock
      inoculated) and Fusarium oxysporum treated plants. The degradome library
      consisted of both control and treated samples which were pooled together during
      library preparation and named as D4. The D4 dataset have been deposited at
      GenBank under accession number SRX3921398,
      https://www.ncbi.nlm.nih.gov/sra/SRX3921398.

PMID- 30197912
TI  - Data on beetle-killed and surviving lodgepole pine (Pinus contorta) radial growth
      from the Beaverhead-Deerlodge National Forest, MT prior to a severe mountain pine
      beetle outbreak.
AB  - This article contains measurements of raw radial growth, distance to pith, and
      calculated basal area increments (BAI) from 444 5-mm increment cores (237 trees)
      collected in July 2016 from the Beaverhead-Deerlodge National Forest, MT. These
      data were used for the study presented in "Mountain pine beetle attack faster
      growing lodgepole pine at low elevations in western Montana, USA" [1]. Plot
      locations where increment cores were taken as well as code to calculate BAI are
      also included. Cores were collected from lodgepole pine (Pinus contorta) trees
      that were killed during a recent bark beetle outbreak (220 cores; 117 trees) as
      well as trees that survived the outbreak (210 cores; 113 trees) in twelve stands
      spanning north and south aspects and three elevational bands along a 600-m
      gradient. 14 additional cores were collected from 7 strip-attacked trees.
      Increment cores were prepared and measured using standard dendrochronological
      techniques, "An Introduction to Tree-Ring Dating" [2]. Master chronologies for
      each aspect-elevation combination were created using approximately ten cores from
      surviving trees at each location. Cores were cross-dated, then scanned at 2400
      dpi. Annual ring widths were measured using CooRecorder 7.7, "Cybis Electronic,
      CDendro and CooRecorder V.7.7" [3], and final chronologies were quantitatively
      validated in COFECHA, "Computer-assisted quality control in tree-ring dating and
      measurement, Tree-Ring Society" [4].

PMID- 30197913
TI  - Proteomic and functional data sets on synaptic mitochondria from rats with
      genetic ablation of Parkin.
AB  - In this paper, we provide proteomic and functional data for synaptic mitochondria
      from the striatum of rats with Parkin ablation. The quantitative proteomic data
      was obtained using SWATH-MS methodology and mitochondrial function was assessed
      through measurement of oxygen consumption rate using the Seahorse XF Analyzer.
      This data facilitates comparisons with previous proteomic and functional data
      obtained using the exact same methods. A complete set of proteomic data is
      contained in Supplementary Table 1.

PMID- 30197914
TI  - Phytochemical screening and antioxidant parameters data in prostatic rats fed
      with Laportea aestuans leaves.
AB  - Several plants have been used in ancient times as medicines to treat, manage and
      prevent many diseases in various traditional settings throughout the world. The
      effect of administration of hydro-ethanolic extract of Laportea aestuans (La)
      leaves at different doses in Wistar rats induced with benign prostatic
      hyperplasia (BPH) using antioxidant parameters and phytochemical screening data
      was obtained. Thirty (30) animals were randomly divided into six (6) groups (A-F)
      of five (5) animals each. BPH was induced in the animals by daily subcutaneous
      injection of testosterone propionate (TP) (3 mg/kg) in olive oil and
      administration of treatments for four (4) weeks were done concurrently. Group A
      received olive oil alone subcutaneously, group B was induced with BPH alone,
      groups C-E were induced with BPH but received different doses of La at 100, 200
      and 400 mg/kg. Lastly, group F was induced with BPH but treated with finasteride
      (5 mg/kg) which serves as the positive control group. Phytochemical screening
      data of saponins, flavonoids (0.5010 +/- 0.0009 mg/ml), alkaloids (0.528 mg/ml),
      phenols (0.6195 +/- 0.0015 mg/ml), tannins (0.5410 +/- 0.0013 mg/ml) and steroids
      (1.6230 +/- 0.0210 mg/ml) in hydro-ethanolic extract of La. Antioxidant
      parameters such as superoxide dismutase, catalase and reduced glutathione data
      were alsou gotten at 400 mg/kg La (48.1 +/- 4.17U/mg protein), (29.43 +/-
      1.38U/mg protein) and (30.60 +/- 2.05 ug/ml) respectively when compared to the
      BPH group (35.5 +/- 0.97U/mg protein), (11.36 +/- 2.39U/mg protein) and (15.60 +/
      1.14 ug/ml).

PMID- 30197915
TI  - Technical data of a grid-connected photovoltaic/wind hybrid system with and
      without storage battery for residential buildings located in a warm area.
AB  - Electric production data of a grid-connected hybrid system are presented. The
      system consists of a photovoltaic generator, a wind micro-generator in the
      presence (HPWBS) or absence (HPWS) of an electric storage system. In such a
      system, the power generated by RES (renewable energy sources) is sent directly to
      balance the load. A residential use has been analysed in warm climate. The
      analysis has been carried out by TRNSYS 17 (Transient System Simulation) software
      and the mathematical modelling and the energy balance of the system have been
      shown in Mazzeo et al. (2018). The annual energy performance has been evaluated,
      in terms of dimensionless balance of the generated energy and dimensionless
      balance of the energy required by the load, for 375 hybrid system configurations.
      These configurations were obtained by varying the photovoltaic power, the wind
      power and the battery storage capacity, considering different hourly average
      daily values of the load.

PMID- 30197916
TI  - Survey data on political attitudes of China's urban residents compiled from the
      Chinese General Social Survey (CGSS).
AB  - The data discussed in this article is related to the article entitled "Identity
      and trust in government: A comparison of locals and migrants in urban China" (Niu
      and Zhao, 2018) [1], which analyses the political trust among three groups of
      urban residents in China (rural-urban migrants, urban-urban migrants, and urban
      locals) based on a sample with 4059 observations extracted from the 2010 Chinese
      General Social Survey (CGSS). The dataset contains detailed information on
      respondents' political and social attitudes, demographic characteristics, and
      socio-economic status.

PMID- 30197917
TI  - Data on cell survival, apoptosis, ceramide metabolism and oxidative stress in A
      494 renal cell carcinoma cell line treated with hesperetin and hesperetin-7-O
      acetate.
AB  - Ceramide pathway is a key regulator in cell proliferation and apoptosis and
      oxidative stress up-regulate ceramides. Acid ceramidase (ACDase), neutral
      sphingomyelinase (NSMase) and glucosylceramide synthase (GCS) are critical
      enzymatic systems in ceramide metabolism. Our data represent the comparative
      assessment of Hesperetin (Hst) and hesperetin-7-O-acetate (HTA) effects on A-494
      renal carcinoma cells include cell survival, caspase-3 and 9 activities, total
      cellular ceramide and the activities of ACDase, NSMase, GCS and superoxide
      dismutase (SOD). Data reveals potentiating effects of both HTA and Hst on
      ceramide pathway and may offer a novel tool in human renal cell carcinoma
      therapy.

PMID- 30197918
TI  - Microbiological dataset of rural drinking water supplies in Zahedan, Iran.
AB  - The residual chlorine and microbial quality of drinking water in the Zahedan
      villages by a number of1221 samples from all 168 villages were collected between
      2014-2015. Then the samples were evaluated using 9-tube fermentation methods and
      portable chlorine method test. Based on the microbial coliform and fecal coliform
      indices, the data indicated that the maximum and minimum controlling of the
      bacteria in the distribution network were in the winter (90.62%) and autumn
      (85.56%), respectively. Also in the reservoirs, the maximum and minimum
      controlling of the bacteria were in winter (93.49%) and autumn (87.35%),
      respectively. The residual chlorine was prepared in almost all of seasons.

PMID- 30197920
TI  - Longitudinal data for magnetic susceptibility of normative human brain
      development and aging over the lifespan.
AB  - The data presented in this article accompany the research article entitled
      "Longitudinal Atlas for Normative Human Brain Development and Aging over the
      Lifespan using Quantitative Susceptibility Mapping" (Zhang et al., 2018) [1]. The
      longitudinal evolution of magnetic susceptibility in human brain indicates
      critical characteristics of normal brain development and aging. In the
      corresponding research article, we build longitudinal QSM atlases over various
      age intervals using 166 healthy subjects (83F/69M) with an age range of 1-83
      years old. Based on the newly built atlases, we investigate the regional
      evolutions of magnetic susceptibility in the brain. In this article, we report
      anatomical evolutions of the age-specific QSM atlases in deep gray matter nuclei
      and in two selected white matter fiber bundles. In addition to iron-rich brain
      nuclei, the evolution patterns of the magnetic susceptibility in the amygdala and
      hippocampus are also presented.

PMID- 30197921
TI  - Phenology, nectar dynamics and reproductive success of Inga vera (Leguminosae) in
      monospecific plantations and forest remnants in Atlantic forest: Dataset
      exploration.
AB  - Distinct approaches have been adopted for tropical forest restoration in the last
      decades. The long-term viability of these restored forests and their capacity to
      provide the required services demand continuous evaluation to guide future
      initiatives. In addition, the resilience and maintenance of plant and animals
      communities in restored forests in tropical regions are closely related to the
      recovery of animal-mediated interactions. We provide, in this article, raw data
      related to the reproductive ecology of Inga vera, one of the most common tree
      species used in forest restoration initiatives in the Brazilian northeastern
      Atlantic forest. Specifically, we explore data on phenology, nectar dynamics and
      reproductive success of I. vera in natural and planted (monospecific)
      populations. This data article is related to the research article "Pollination
      partial recovery across monospecific plantations of a native tree (Inga vera,
      Leguminosae) in the Atlantic forest: lessons for restoration" (Cruz-Neto et al.,
      2018) [1].

PMID- 30197919
TI  - Data on whole genome sequencing of extrapulmonary tuberculosis clinical isolates
      from India.
AB  - This article describes the whole genome sequencing data from 5 extrapulmonary
      tuberculosis clinical isolates. The whole genome sequencing was carried out on
      Illumina MiSeq platform to identify single nucleotide variations (SNVs)
      associated with drug resistance. A total of 214 SNVs in the coding and promoter
      regions were identified in the whole genome sequencing analysis. Among the
      identified SNVs, 18 SNVs were identified in genes known to be associated with
      first and second line drug resistance. The data is related to the research
      article "Whole genome sequencing of Mycobacterium tuberculosis isolates from
      extrapulmonary sites" (Sharma et al., 2017) [1].

PMID- 30197922
TI  - Prostate specific antigen and relative prostate weight data on effect of
      Tetracarpidium conophorum leaf extract on testosterone-induced benign prostatic
      hyperplasia.
AB  - Benign prostatic hyperplasia (BPH) is a common urological disorder of men,
      characterized by prostatic enlargement and urethral obstruction. In this study,
      BPH was induced in experimental groups by daily subcutaneous injections of
      testosterone propionate (TP) for 3 weeks. Tetracarpidium conophorum was
      administered daily by oral gavage at a dose of 100, 200 and 400 mg/kg BW of
      extract for three weeks, along with the TP injections and 5 mg/kg of finasteride
      for comparison. On day 21, the animals were sacrificed after anesthesia. Prostate
      were excised, weighed and used to determine relative prostate weight.
      Quantitative and qualitative phytochemical screening was also done and it showed
      the presence of flavonoids (0.370 mg/ml), tannins (0.458 mg/ml), phenols (0.508
      mg/ml) and steroids (0.257 mg/ml). The prostate specific antigen level was
      evaluated, the result showed the data for extract group 200 mg/kg, 400 mg/kg,
      finasteride control group and BPH control group to be 0.186 +/- 0.0023 ng/ml,
      0.153 +/- 0.005 ng/ml, 0.119 +/- 0.0125 ng/ml and 0.332 +/- 0.004 ng/ml
      respectively.

PMID- 30197923
TI  - New WGS data and annotation of the heterosomal vs. autosomal localization of
      Ostrinia scapulalis (Lepidoptera, Crambidae) nuclear genomic scaffolds.
AB  - Here, we introduce new whole-genome shotgun sequencing and annotation data
      describing the autosomal vs. Z-heterosomal localization of nuclear genomic
      scaffolds of the moth species Ostrinia scapulalis. Four WGS libraries
      (corresponding to 2 males and 2 females) were sequenced with an Illumina
      HiSeq2500 sequencing technology, and the so-called 'AD-ratio' method was applied
      to distinguish between autosomal and Z-heterosomal scaffolds based on sequencing
      depth comparisons between homogametic (male) and heterogametic (female)
      libraries. A total of 25,760 scaffolds (corresponding to 341.69 Mb) were labelled
      as autosomal and 1273 scaffolds (15.29 Mb) were labelled as Z-heterosomal,
      totaling about 357 Mb. Besides, 4874 scaffolds (29.07 Mb) remain ambiguous
      because of a lack of AD-ratio reproducibility between the two replicates. The
      annotation method was evaluated a posteriori, by comparing depth-based annotation
      with the exact localization of known genes. Raw genomic data have been deposited
      and made accessible via the EMBL ENA BioProject id PRJEB26557. Comprehensive
      annotation is made accessible via the LepidoDB database
      (http://bipaa.genouest.org/sp/ostrinia_scapulalis/download/genome/v1.2/).

PMID- 30197924
TI  - Dataset describing ethanol and 1,2-propanediol production by a stenothermal
      moderately thermophilic anaerobe, Clostridium strain AK1.
AB  - The dataset details the fermentation of D-glucose, L-rhamnose, and L-fucose and
      their end-product formation by the moderate thermophile Clostridium strain AK1
      (DSM 18778) as related to the work described in "Propanediol from L-rhamnose
      using the moderately thermophilic Clostridium strain AK1" [1]. The influence of
      culture conditions on end product formation from D-glucose and L-rhamnose by AK1
      was investigated in batch culture. Strain AK1 was cultivated at initial substrate
      concentrations varying from 0 to 60 mM and initial pH values varying from 4.5 to
      8.5. Additionally different cultivation temperatures (30-65  degrees C), the
      influence of liquid-gas phase ratio as well as different phosphate concentrations
      on growth were investigated.

PMID- 30197925
TI  - Establishing research priorities to improve the One Health efficacy of Australian
      general practitioners and veterinarians with regard to zoonoses: A modified
      Delphi survey.
AB  - While general medical practitioners (GPs) and veterinarians are often the first
      line responders in the face of a disease outbreak, pathways to improving the One
      Health efficacy of these clinicians remain unclear. A two-phase modified Delphi
      survey of professionals with known expertise in One Health ('expert panel') was
      used to 1) identify key knowledge, attitudes and practices (KAPs) of GPs and
      veterinarians that would be consistent with a One Health approach to zoonoses;
      and 2) determine priorities for future surveys with Australian GPs and
      veterinarians to identify important gaps that impede effective diagnosis and
      management of zoonoses. A list of 13 topics/sub-topics, as well as a list of 25
      specific zoonotic diseases/agents emerged from the first phase of the survey. In
      the second phase the expert panel identified general knowledge of the clinical
      aspects and epidemiological aspects of zoonoses, as well as risk management
      practices, as the most important KAPs and research priorities for both GPs and
      veterinarians. In terms of diseases, the expert panel regarded knowledge of
      Hendra virus, Q fever, Australian bat lyssavirus (ABLV), anthrax and Brucella
      suis most important for veterinarians, whilst for GPs, Q fever,
      gastrointestinal/foodborne diseases, influenza, ABLV and local vector-borne
      diseases were found to be most important by the expert panel. Some differences
      were noted in terms of prioritization of topics/sub-topics and diseases/agents
      according to expert background (veterinary and non-veterinary). The Delphi survey
      technique enabled efficient collection of data from a diverse range of One Health
      'experts'/specialists and provided clear priorities for proposed future research,
      and potentially for educational interventions to improve One Health efficacy of
      clinicians.

PMID- 30197926
TI  - Isolation, Characterisation and Identification of Plant Growth Promoting
      Rhizobacteria from Cauliflower (Brassica oleracea).
AB  - Bio-fertilizers are currently being considered as effective and environmentally
      safe alternatives to synthetic fertilizers. In recent years, the use of many
      Rhizobia in the growth of many plants has found commercial utilization in
      developing countries especially as growth promoters. This study was conducted to
      isolate Rhizobacteria from the rhizosphere, rhizoplane and endorhizosphere of
      cauliflower (Brasicca oleracea) collected from ChattaBakhtawar, Islamabad,
      Pakistan. Extraction of rhizobacteria was done and the composition was maintained
      accordingly as for biofertilizers. Luria-Bertini (LB) media was used to isolate
      rhizobacterial strains and the identification of rhizobacteria was done by
      studying many morphological characteristics of colonies growing on the media.
      These characteristics include Form, Elevation, Margin, Opacity and Colour; these
      were recorded periodically. For the confirmation of rhizobacteria; biochemical
      tests were performed. Gram staining was done for 14 strains CF-ES-4, CF-ES-5A, CF
      ES-5B, CF-ES-5C, CF-ES-6A, CF-ES-6B, CF-RP-4C, CF-RP-4B, CF-RP-6, CF-RP-5A, CF-RP
      4, CF-RS -4, CF-RS-5, and CF-RS-6: Among these, 11 strains were Gram negative
      while the 3 strains CF-RP-5A, CF-ES-5A and CF-RP-4 were Gram positive. The
      strains which were phosphate negative were: CF-RP-4C, CF-RS-8, CF-RP-4A, CF-ES-4,
      CF-RS-7, CF-ES-5C, CF-RP-6 while the CF-RP-5A CF-RP-5B, CF-ES-5B, CF-ES-5A, CF-RP
      4B, CF-ES-6B, CF-RS-4 and CF-RS-6 strains were phosphate positive; these
      confirmed qualities of rhizobacteria. Taken together, the present investigation
      adds more information to current understanding of Nitrogen-fixing by
      rhizobacteria; and will be useful for the commercialization of these strains to
      improve the yield of economic plants like cauliflower. Thus, identification of
      strains to species level and field studies are recommended before adoption by
      farmers in agricultural field practices.

PMID- 30197927
TI  - Examining Barriers as Risk Factors for Relapse: A focus on the Canadian Treatment
      and Recovery System of Care.
AB  - Objectives: In 2016, the Canadian Centre on Substance Use and Addiction (CCSA)
      conducted the first survey of individuals in recovery from addiction in Canada.
      The findings revealed that many individuals in recovery lead meaningful lives,
      contributing to their families and society. However, participants also identified
      a number of barriers to starting and maintaining recovery. The current study
      examined the relationship between the barriers experienced and relapse during
      recovery. Methods: Data from the 2016 Life in Recovery (LIR) from Addiction in
      Canada survey were analyzed using descriptive and logistic regression analyses.
      Participants comprised 855 individuals (Mage = 47.3 years), all of whom self
      reported being in recovery from addiction. Results: Logistic regressions revealed
      that upon starting recovery, long delays for treatment, odds ratio (OR) = 1.77,
      95% confidence interval (CI) = 1.21-2.60, P < 0.01, and not having stable
      housing, OR = 1.83, 95% CI = 1.14-2.95, P < 0.05, were associated with increased
      risk of relapse. Moreover, upon examining barriers to maintaining recovery, a
      lack of supportive social networks, OR = 2.10, 95% CI = 1.26-3.48, p < 0.01, a
      lack of programs or supports, OR = 1.75, 95% CI = 1.03-2.98, P < 0.05, and the
      costs of recovery services OR = 1.73, 95% CI = 1.02-2.91, P < 0.05 were
      associated with increased risk of relapse. Conclusions: Targeted investments to
      address the treatment-related barriers that most strongly relate to relapse,
      could significantly improve the lives of individuals struggling with addiction
      and those beginning and maintaining their recovery journey. Objectifs: En 2016,
      le Centre canadien de lutte contre l'alcoolisme et les toxicomanies (CCLAT) a
      mene un premier sondage aupres des personnes en retablissement a la suite d'une
      dependance au Canada. Les resultats ont revele que de nombreuses personnes en
      retablissement menent des vies significatives, contribuant ainsi a leur famille
      et a la societe. Cependant, les participants ont egalement identifie un certain
      nombre d'obstacles au demarrage et au maintien du retablissement. La presente
      etude a examine la relation entre les obstacles rencontres et la rechute pendant
      le retablissement. Methodes: Les donnees de l'enquete Life in Recovery (LIR) de
      l'Enquete sur la toxicomanie au Canada de 2016 ont ete analysees a l'aide
      d'analyses de regression descriptives et logistiques. Les participants
      comprenaient 855 individus (Moyenne d'age = 47,3 ans), qui ont tous declare etre
      en retablissement apres une dependance. Resultats: Les regressions logistiques
      ont revele qu'au debut du retablissement, de longs delais de traitement, chance
      de reussite (CR) = 1,77, intervalle de confiance a 95% (IC) = 1,21-2,60, p <
      0,01, et n'ayant pas de logement stable, CR = 1,83, IC 95% = 1,14-2,95, p < 0,05,
      etaient associes a un risque accru de rechute. De plus, en examinant les
      obstacles au maintien du retablissement, un manque de reseaux sociaux de soutien,
      CR = 2.10, IC a 95% = 1.26-3.48, p < 0.01, manque de programmes ou de soutien, CR
      = 1.75, IC a 95% = 1.03-2,98, p < 0,05, et les coUts des services de recuperation
      CR = 1,73, IC 95% = 1,02-2,91, p < 0,05 etaient associes a un risque accru de
      rechute. Conclusions: Des investissements cibles visant a surmonter les obstacles
      lies au traitement les plus etroitement lies a la rechute pourraient ameliorer
      considerablement la vie des personnes aux prises avec une dependance et de celles
      qui amorcent et poursuivent leur chemin vers le retablissement.

PMID- 30197928
TI  - Why Is It so Hard to Do Good Science?
AB  - "Good science" means answering important questions convincingly, a challenging
      endeavor under the best of circumstances. Our inability to replicate many
      biomedical studies has been the subject of numerous commentaries both in the
      scientific and lay press. In response, statistics has re-emerged as a necessary
      tool to improve the objectivity of study conclusions. However, psychological
      aspects of decision making introduce preconceived preferences into scientific
      judgment that cannot be eliminated by any statistical method. The psychology of
      decision making, expounded by Kahneman, Tversky, and Thayer, is well known in the
      field of economics, but the underlying concepts of cognitive psychology are also
      relevant to scientific judgments. I repeated experiments carried out on
      undergraduates by Kahneman and colleagues four to five decades ago, but with
      scientists, and obtained essentially the same results. The experiments were in
      the form of written reactions to scenarios, and participants were scientists at
      all career stages. The findings reinforce the roles that two inherent intuitions
      play in scientific decision making: our drive to create a coherent narrative from
      new data regardless of its quality or relevance and our inclination to seek
      patterns in data whether they exist or not. Moreover, we do not always consider
      how likely a result is regardless of its p value. Low statistical power and
      inattention to principles underpinning Bayesian statistics reduce experimental
      rigor, but mitigating skills can be learned. Overcoming our natural human
      tendency to make quick decisions and jump to conclusions is a deeper obstacle to
      doing good science; this too can be learned.

PMID- 30197929
TI  - Amyloid beta accumulation in HIV-1 infected brain: the role of altered
      cholesterol homeostasis.
AB  - The long-term survival of HIV-1 infected individuals credited to the availability
      and use of effective antiretroviral therapy (ART) is unfortunately now
      accompanied by an almost 50% prevalence of HIV-1 associated neurocognitive
      disorder (HAND). Increasingly, it has been realized that HIV-1 infected people on
      ART have clinical and pathological observations of Alzheimer's disease (AD)-like
      manifestations including neurocognitive problems, intraneuronal accumulation of
      amyloid beta (Abeta) protein, and disturbed synaptic integrity. Part of the
      current challenge facing the medical community and people living with HIV-1
      infection is that the pathogenesis of HAND remains unclear, and little is known
      about how AD-like pathology is developed as a result of HIV-1 infection and/or
      long-term ART treatment. Here we discuss the potential role of altered plasma
      cholesterol homeostasis, a prominent feature of HIV-1 infection, on the
      development of intraneuronal Abeta accumulation in HIV-1 infected brain. We
      speculate that elevated plasma LDL cholesterol, once it enters brain parenchyma
      via an increasingly leaky BBB, can be internalized by neurons via receptor
      mediated endocytosis, a process that could promote internalization of amyloid
      beta precursor protein (AbetaPP). Unlike brain in situ synthesized apoE
      cholesterol, apoB-containing LDL-cholesterol could lead to cholesterol
      accumulation thus disturbing neuronal endolysosome function and ultimately the
      accumulation of intraneuronal Abeta in HIV-1 infected brain.

PMID- 30197930
TI  - Construction of an overexpression library for Mycobacterium tuberculosis.
AB  - There is a pressing need to develop novel anti-tubercular drugs. High-throughput
      phenotypic screening yields chemical series that inhibit bacterial growth. Target
      identification for such series is challenging, but necessary for optimization of
      target engagement and the development of series into clinical drugs. We
      constructed a library of recombinant Mycobacterium tuberculosis strains each
      expressing a single protein from an inducible promoter as a tool for target
      identification. The library of 1733 clones was arrayed in 96-well plates for
      rapid screening and monitoring growth. The library contains the majority of the
      annotated essential genes as well as genes involved in cell wall and fatty acid
      biosynthesis, virulence factors, regulatory proteins, efflux, and respiration
      pathways. We evaluated the growth kinetics and plasmid stability over three
      passages for each clone in the library. We determined expression levels (mRNA
      and/or protein) in 396 selected clones. We screened the entire library and
      identified the Alr-expressing clone as the only recombinant strain, which grew in
      the presence of d-cycloserine (DCS). We confirmed that the Alr-expressing clone
      was resistant to DCS (7-fold shift in minimum inhibitory concentration). The
      library represents a new tool that can be used to screen for compound resistance
      and other phenotypes.

PMID- 30197931
TI  - Log D analysis using dynamic approach.
AB  - Log D the logarithm ( log10 ) of the distribution coefficient ( D ), is one of
      the important parameters used in Lipinski's rule to assess the druggability of a
      molecule in pharmaceutical formulations. The distribution of a molecule between a
      hydrophobic organic phase and an aqueous buffer phase is influenced by the pH of
      the buffer system. In this work, we used both the conventional algebraic method
      and the generalized 'dynamic' approach to model the distribution coefficient of
      amphoteric, diamino-monoprotic molecule and monoprotic acid in the presence of
      salt or co-solvent. We have shown the equivalence of these methods by analysing
      the recently reported experimental data of amphoteric molecules such as nalidixic
      acid, mebendazole, benazepril and telmisartan.

PMID- 30197932
TI  - Multi-technique analysis of precipitable water vapor estimates in the sub-Sahel
      West Africa.
AB  - Precipitable water vapor (PWV) is an important climate parameter indicative of
      available moisture in the atmosphere; it is also an important greenhouse gas.
      Observations of precipitable water vapor in sub-Sahel West Africa are almost non
      existent. Several Aerosol Robotic Network (AERONET) sites have been established
      across West Africa, and observations from four of them, namely, Ilorin (4.34
      degrees  E, 8.32 degrees  N), Cinzana (5.93 degrees  W, 13.28 degrees  N),
      Banizoumbou (2.67 degrees  E, 13.54 degrees  N) and Dakar (16.96 degrees  W,
      14.39 degrees  N) are being used in this study. Data spanning the period from
      2004 to 2014 have been selected; they include conventional humidity parameters,
      remotely sensed aerosol and precipitable water information and numerical model
      outputs. Since in Africa, only conventional information on humidity parameters is
      available, it is important to utilize the unique observations from the AERONET
      network to calibrate empirical formulas frequently used to estimate precipitable
      water vapor from humidity measurements. An empirical formula of the form
      PWV=aTd+b where Td is the surface dew point temperature, a and b are constants,
      was fitted to the data and is proposed as applicable to the climatic condition of
      the sub-Sahel. Moreover, we have also used the AERONET information to evaluate
      the capabilities of well-established numerical weather prediction (NWP) models
      such as ERA Interim Reanalysis, NCEP-DOE Reanalysis II and NCEP-CFSR, to estimate
      precipitable water vapor in the sub-Sahel West Africa; it was found that the
      models tend to overestimate the amount of precipitable water at the selected
      sites by about 25 %.

PMID- 30197934
TI  - The 2017 American Society of Radiation Oncology (ASTRO) annual meeting: Taking a
      deeper dive into social media.

PMID- 30197933
TI  - Recruiting young pre-symptomatic children for a clinical trial in type 1
      diabetes: Insights from the Fr1da insulin intervention study.
AB  - Background: Although detection of children at high risk of developing type 1
      diabetes and diagnosis of early stages is possible, up to now there exists no
      approved therapy to delay or prevent type 1 diabetes. Thus it is vital to develop
      evidence-based interventions. For this a sufficient number of trial participants
      is crucial but difficult to obtain especially in asymptomatic children. Aim:
      Identifying family characteristics that lead to or impede trial participation and
      analyze reasons stated by families for non-participation. Methods: Participants
      for the Fr1da Insulin Intervention study are recruited from the Fr1da study, a
      population based screening for early stage type 1 diabetes in Bavaria. Families
      with eligible children were invited to enroll. We analyzed sex and age of the
      child, distance of the family to the study center in Munich and the existence of
      a first degree family member with type 1 as possible influential factors for
      study participation. We also analyzed reasons stated by families who declined
      study participation in a phone interview. Results: Of 146 eligible children 77
      (53%) were enrolled into the trial. None of the tested family characteristics
      differed significantly between the enrolling and the families not participating,
      but in general enrolling families lived closer to the study site than families
      not participating. This is also reflected in the reasons given by non
      participating families. The most frequent reason stated were time restrictions.
      The second most frequent reason was the venous blood draw. Conclusion: The
      factors for non-participation identified in this project need be taken into
      account for the design of future trials in young children to ensure proper
      recruitment and thus to generate valid results for medical treatment of children.
      More research on the reason of participation and non-participation in clinical
      trials is needed.

PMID- 30197935
TI  - Resident satisfaction with radiation oncology training.
AB  - Purpose: Residency training environments can differ significantly; therefore,
      resident satisfaction may vary widely among programs. Here, we sought to examine
      several variables in program satisfaction through a survey of radiation oncology
      (RO) trainees in the United States. Methods and materials: An anonymous,
      institutional review board-approved, internet-based survey was developed and
      distributed to U.S. residents in RO in September 2016. This email-based survey
      assessed program-specific factors with regard to workload, work-life balance, and
      education as well as resident-specific factors such as marital status and
      postgraduate year. Binomial multivariable regression assessed the correlations
      between these factors and the endpoint of resident-reported likelihood of
      selecting an alternative RO residency program if given the choice again. Results:
      A total of 215 residents completed the required survey sections, representing
      29.3% of U.S. RO residents. When asked whether residency allowed for an adequate
      balance between work and personal life, the majority of residents (75.6%) agreed
      or strongly agreed, but a minority (9.3%) did not feel that residency allowed for
      sufficient time for personal life. The majority of residents (69.7%) indicated
      that they would choose the same residency program again, but 12.2% would have
      made a different choice. Almost three-fourths of residents (73.0%) felt that
      faculty and staff cared about the educational success of residents, but 9.27% did
      not. Binomial multivariable regression revealed that senior residents (odds
      ratio: 6.70; 95% confidence interval, 2.20-22.4) were more likely to desire a
      different residency program. In contrast, residents who reported constructive
      feedback use by the residency program (odds ratio:0.22; 95% confidence interval,
      0.06-0.91) were more satisfied with their program choice. Conclusions: Most RO
      residents reported satisfaction with their choice of residency program, but
      seniors had higher rates of dissatisfaction. Possible interventions to improve
      professional satisfaction include incorporating constructive resident feedback to
      enhance the program. The potential impact of job market pressures on seniors
      should be further explored.

PMID- 30197936
TI  - Updated strategies in the treatment of benign diseases-a patterns of care study
      of the german cooperative group on benign diseases.
AB  - Purpose: Radiation therapy (RT) is a common treatment for benign diseases in
      Germany. Because the treatment concepts are inconsistent, we conducted this
      pattern-of-care study on behalf of the German Cooperative Group on Benign
      Diseases to evaluate treatment standards in Germany. Methods and materials:
      Questionnaires were mailed to all radiation therapy facilities in Germany. We
      assessed the treatment equipment, annual number of patients, treatment
      indications, and, in particular, treatment strategies in patients with benign
      diseases in 2014. Results: We evaluated questionnaires returned by 116
      participating institutions, of which 41 were ambulatory health care centers, 28
      were private institutions, 27 were community hospitals, and 20 were university
      hospitals. On average, 2 linac accelerators and 2 megavoltage units were
      available in each institution. In 2014, a total of 36,830 patients were treated
      for benign diseases: 16,989 for degenerative diseases (peritendinitis
      humeroscapularis n = 2691; epicondylitis humeri n = 3788; heel spur n = 10,510);
      14,936 for osteoarthritis (coxarthrosis n = 2230; gonarthrosis n = 2623;
      omarthrosis n = 2691; rhizarthrosis n = 2440; polyarthrosis n = 2297; others n =
      2655); 1563 for hyperproliferative diseases (morbus Dupuytren n = 960; morbus
      Ledderhose n = 441; keloids n = 139; pterygium of the conjunctiva n = 3; other
      hyperproliferative diseases n = 20); 2440 for functional disorders (gynecomastia
      n = 843; Graves' disease n = 205; lymphatic fistula n = 178; heterotopic
      ossification prophylaxis n = 1214); 859 for stereotactic RT in the central
      nervous system (arteriovenous malformation n = 53; meningioma n = 425; acoustic
      neuroma n = 201; pituitary adenoma n = 131; others n = 49), and 43 for rare
      indications (pigmented villonodular synovitis n = 20 or vertebral hemangioma n =
      23). The mean whole dose was <10 Gy in the treatment of degenerative disorders,
      25 Gy for hyperproliferative diseases, 15 Gy for functional disorders, and <50 Gy
      for stereotactic RT. Conclusions: In 2014, RT had an important role in the
      treatment of benign diseases. Because treatment concepts are inherent, we
      recommend treatment based on the guidelines written by the German Cooperative
      Group on Benign Diseases.

PMID- 30197937
TI  - A component of lobular carcinoma in clinically lymph node-negative patients
      predicts for an increased likelihood of upstaging to pathologic stage III breast
      cancer.
AB  - Purpose: Physical examination and diagnostic imaging are often less precise in
      determining the extent of disease in invasive lobular carcinoma (ILC) relative to
      nonlobular histologies. Anecdotally, surgical axillary evaluation frequently
      reveals positive lymph nodes in clinically N0 patients with ILC; however, few
      studies quantify the likelihood of finding unsuspected disease at the time of
      surgery. In this study, we evaluate whether the presence of lobular histology
      increases the incidence of surgical upstaging to pathologic stage IIIA or greater
      in patients with a clinically node-negative axilla and positive sentinel lymph
      node (SLN) biopsy. Methods and materials: We examined patients from our
      institution between 1997 and 2009 treated specifically with mastectomy, SLN
      biopsy, and completion axillary lymph node dissection due to a positive SLN. For
      analysis, patients were grouped according to the presence of any lobular
      component on surgical pathology. The number of total positive lymph nodes, cancer
      stage, age, final tumor size, and ER/PR/HER2 status were assessed based on tumor
      histology. Results: We evaluated 345 previously untreated women with clinical T0
      T2 and N0 disease at the time of surgery. A total of 110 patients (32%) had a
      component of ILC on surgical pathology. In addition, 295 patients (85.5%) had ER
      + breast carcinoma, 243 (70.4%) had PR + disease, 56 (16.2%) were HER2 + , and 28
      (8.1%) were triple negative. At the time of surgery, women with lobular disease
      were observed to have a greater number of positive lymph nodes (2.79 vs 2.26; P =
      .009) and were more frequently upstaged to at least pathologic stage IIIA
      compared with nonlobular patients (30.9% vs 17.4%; P = .007). Conclusions: In
      this cohort, patients with a component of lobular carcinoma were more often
      surgically upstaged to pathologic stage IIIA or higher, which is a classical
      indication for postmastectomy radiation therapy. Our findings suggest that ILC is
      often more extensive than it appears clinically and has significant implications
      for management of patients with lobular carcinoma after the discovery of a
      positive SLN.

PMID- 30197938
TI  - Is completion axillary lymph node dissection necessary in patients who are
      underrepresented in the ACOSOG Z0011 trial?
AB  - Purpose: The American College of Surgeons Oncology Group trial Z0011 demonstrated
      that axillary node dissection (ALND) can be omitted in patients managed with
      breast conserving surgery and 1 to 2 positive sentinel lymph nodes (SLNs) without
      adverse effects on locoregional recurrence or disease-free survival (DFS). We
      investigated patients with breast cancer for whom clinicopathologic features were
      underrepresented in the Z0011 trial and analyzed radiation therapy treatment
      patterns and clinical outcomes. Methods and materials: We retrospectively
      reviewed records of patients who underwent a lumpectomy and SLN biopsy with
      positive SLNs but not an ALND and completed adjuvant radiation therapy. Eligible
      patients had T3 tumors, >2 positive SLNs, invasive lobular carcinoma, estrogen
      receptor negative status, extranodal extension, Nottingham Grade 3, or were age
      <50 years. Results: We identified 105 women treated between July 2011 and July
      2016 with a median follow-up time of 48.5 months (Range, 11-83 months). There
      were 40 women with an extranodal extension (38.9%) and 42 women with grade 3
      disease (40.0%). Nineteen patients received whole breast irradiation alone
      (18.1%) and 86 patients were treated with modified tangent fields including the
      superior axilla level I/II (81.9%). Thirty-three patients (31.4%) also received a
      3rd supraclavicular, nodal-directed field. Among the 86 patients who received
      axillary nodal irradiation, nodal volume contouring was performed in 77 patients
      (89.5%). Fifty-one patients (48.6%) also received adjuvant chemotherapy. The
      overall rates of 4-year DFS and locoregional control (LRC) were 94.3% and 98.1%,
      respectively. Off all patients, 1 patient experienced an internal mammary nodal
      recurrence, another patient a contralateral breast tumor, and two patients
      distant metastases. There were no axillary or ipsilateral breast tumor
      recurrences. Conclusions: This retrospective analysis of women who were
      underrepresented or excluded from the Z11 trial and underwent a lumpectomy and
      SLN biopsy with positive SLNs demonstrated comparable rates of LRC and DFS. The
      high rates of LRC and DFS suggest that completion ALND may be safely omitted in
      this patient population but larger data sets and longer follow-up times are
      needed to confirm this finding.

PMID- 30197939
TI  - Feasibility of definitive chemoradiation therapy with nedaplatin and 5
      fluorouracil in elderly patients with esophageal squamous cell carcinoma: A
      retrospective study.
AB  - Purpose: This study was designed to retrospectively analyze the safety and
      efficacy of chemoradiation therapy with nedaplatin and 5-fluorouracil in elderly
      patients with esophageal squamous cell carcinoma. Methods and materials: Eligible
      patients were aged 76 years or older, had a histopathologic diagnosis of
      esophageal squamous cell carcinoma, and were treated at the Kitasato University
      Hospital between January 2010 and March 2016. Chemotherapy consisted of
      nedaplatin in an intravenous dose of 90 mg/m2 on day 1 and 5-fluorouracil in an
      intravenous dose of 800 mg/m2 on days 1 to 5, repeated every 4 weeks for 2
      cycles. Radiation therapy consisted of 50.4 Gy in 28 fractions for thoracic
      tumors and 61.2 Gy for cervical tumors. Results: Twenty-five patients were
      studied. Patient characteristics were as follows: median age 79 years (range, 76
      85 years), clinical stage I/II/III/IV (7/8/8/2, respectively), and surgically
      resectable/unresectable (17/8, respectively). The completion rates of radiation
      therapy and chemoradiation therapy were 100% and 84%, respectively. Grade >=3
      acute toxicities included neutropenia (76%), leukopenia (72%), thrombocytopenia
      (32%), anemia (28%), anorexia (32%), oral mucositis (20%), febrile neutropenia
      (12%), and esophagitis (8%). Grade >=3 late toxicities included esophageal
      stenosis (12%) and pleural effusion (4%). The complete response rate was 64%. In
      the median follow-up period of 18.9 months, the 1-year overall survival rate was
      68%. Conclusions: Definitive chemoradiation therapy with nedaplatin and 5
      fluorouracil may be a feasible treatment option for elderly patients with
      esophageal squamous cell carcinoma.

PMID- 30197940
TI  - Evaluation of classification and regression tree (CART) model in weight loss
      prediction following head and neck cancer radiation therapy.
AB  - Objective: We explore whether a knowledge-discovery approach building a
      Classification and Regression Tree (CART) prediction model for weight loss (WL)
      in head and neck cancer (HNC) patients treated with radiation therapy (RT) is
      feasible. Methods and materials: HNC patients from 2007 to 2015 were identified
      from a prospectively collected database Oncospace. Two prediction models at
      different time points were developed to predict weight loss >=5 kg at 3 months
      post-RT by CART algorithm: (1) during RT planning using patient demographic,
      delineated dose data, planning target volume-organs at risk shape relationships
      data and (2) at the end of treatment (EOT) using additional on-treatment
      toxicities and quality of life data. Results: Among 391 patients identified, WL
      predictors during RT planning were International Classification of Diseases
      diagnosis; dose to masticatory and superior constrictor muscles, larynx, and
      parotid; and age. At EOT, patient-reported oral intake, diagnosis, N stage,
      nausea, pain, dose to larynx, parotid, and low-dose planning target volume-larynx
      distance were significant predictive factors. The area under the curve during RT
      and EOT was 0.773 and 0.821, respectively. Conclusions: We demonstrate the
      feasibility and potential value of an informatics infrastructure that has
      facilitated insight into the prediction of WL using the CART algorithm. The
      prediction accuracy significantly improved with the inclusion of additional
      treatment-related data and has the potential to be leveraged as a strategy to
      develop a learning health system.

PMID- 30197941
TI  - Preservation of swallowing function with de-intensified chemoradiation therapy
      for HPV-associated oropharyngeal squamous cell carcinoma.
AB  - Purpose: This study aimed to compare the swallowing function in patients with
      human papillomavirus-associated oropharyngeal squamous cell carcinoma treated
      with de-intensified chemoradiation therapy (6 weeks, 60 Gy) versus those
      receiving standard-of-care chemoradiation therapy (7 weeks, 70 Gy). Methods and
      materials: A retrospective review was conducted of 78 patients with human
      papillomavirus-associated oropharyngeal squamous cell carcinoma with modified
      barium swallow studies pretreatment and 6 to 8 weeks posttreatment. The
      swallowing function was objectively scored for penetration, aspiration, and
      pharyngeal residue. Forty patients received de-intensified chemoradiation therapy
      (60 Gy image guided radiation therapy with weekly cisplatin 30 mg/m2) and 38
      patients received standard-of-care chemoradiation therapy (70 Gy image guided
      radiation therapy with chemotherapy of the medical oncologist's choosing).
      Univariate and multivariate analyses were performed to detect differences between
      the cohorts with regard to laryngeal penetration, aspiration, and pharyngeal
      residue. A multivariate logistic regression was used to determine the overall
      effect of treatment on the swallowing function. Patient-reported swallowing
      outcomes in de-intensified cohort were assessed with the European Organisation
      for Research and Treatment of Cancer Quality of Life Module for Head and Neck
      Cancer and the Patient-Reported Outcomes version of the Common Terminology
      Criteria for Adverse Events questionnaires. Results: Patients treated with de
      intensified chemoradiation therapy were associated with a suggestion of lower
      risk of developing overall swallowing dysfunction (odds ratio [OR], 0.62; P =
      .07), laryngeal penetration (OR, 0.63; P = .12), and pharyngeal residue (OR,
      0.61; P = .08). The mean pre- and 2-year post-European Organisation for Research
      and Treatment of Cancer Quality of Life scores pertaining to swallowing (1-4
      scale, higher worse) in the de-intensified cohort were 1.4 and 1.2 for liquids;
      1.2 and 1.1 for purees; 1.5 and 1.7 for solids, 1.0 and 1.3 for choked when
      swallowing; and 9.0 and 10.8 for composite score, respectively. The mean pre- and
      2-year post-Patient-Reported Outcomes version of the Common Terminology Criteria
      for Adverse Events swallowing difficulty scores (1-5 scale, with higher scores
      being worse) were 1.5 and 1.8, respectively. Conclusions: Compared with 7 weeks
      of 70 Gy, 6 weeks of 60 Gy de-intensified chemoradiation therapy appears to
      better preserve the baseline swallowing function (per objective modified barium
      swallow assessment). Patients treated with de-intensified chemoradiation therapy
      reported minimal changes in swallowing function.

PMID- 30197942
TI  - Multiple energy extraction reduces beam delivery time for a synchrotron-based
      proton spot-scanning system.
AB  - Purpose: Multiple energy extraction (MEE) is a technology that was recently
      introduced by Hitachi for its spot-scanning proton treatment system, which allows
      multiple energies to be delivered in a single synchrotron spill. The purpose of
      this paper is to investigate how much beam delivery time (BDT) can be reduced
      with MEE compared with single energy extraction (SEE), in which one energy is
      delivered per spill. Methods and Materials: A recently developed model based on
      BDT measurements of our synchrotron's delivery performance was used to compute
      BDT. The total BDT for 2694 beam deliveries in a cohort of 79 patients treated at
      our institution was computed in both SEE and 9 MEE configurations to determine
      BDT reduction. The cohort BDT reduction was also calculated for hypothetical
      accelerators with increased deliverable charge and compared with the results of
      our current delivery system. Results: A vendor-provided MEE configuration with 4
      energy layers per spill reduced the total BDT on average by 35% (41 seconds)
      compared with SEE, with up to 65% BDT reduction for individual fields. Adding an
      MEE layer reduced the total BDT by <1% of SEE BDT. However, improving charge
      recapture efficiency increased BDT savings by up to 42% of SEE BDT. Conclusions:
      The MEE delivery technique reduced the total BDT by 35%. Increasing the charge
      per spill and charge recapture efficiency is necessary to further reduce BDT and
      thereby take full advantage of our MEE system's potential to improve treatment
      delivery efficiency and operational throughput.

PMID- 30197943
TI  - The virtual cone: A novel technique to generate spherical dose distributions
      using a multileaf collimator and standardized control-point sequence for small
      target radiation surgery.
AB  - Purpose: The study aimed to develop and demonstrate a standardized linear
      accelerator multileaf collimator-based method of delivering small, spherical dose
      distributions suitable for radiosurgical treatment of small targets such as the
      trigeminal nerve. Methods and materials: The virtual cone is composed of a
      multileaf collimator-defined field with the central 2 leaves set to a small gap.
      For 5 table positions, clockwise and counter-clockwise arcs were used with
      collimator angles of 45 and 135 degrees, respectively. The dose per degree was
      proportional to the sine of the gantry angle. The dose distribution was
      calculated by the treatment planning system and measured using radiochromic film
      in a skull phantom for leaf gaps of 1.6, 2.1, and 2.6 mm. Cones with a diameter
      of 4 mm and 5 mm were measured for comparison. Output factor constancy was
      investigated using a parallel-plate chamber. Results: The mean ratio of the
      measured-to-calculated dose was 0.99, 1.03, and 1.05 for 1.6, 2.1, and 2.6 mm
      leaf gaps, respectively. The diameter of the measured (calculated) 50% isodose
      line was 4.9 (4.6) mm, 5.2 (5.1) mm, and 5.5 (5.5) mm for the 1.6, 2.1, and 2.6
      mm leaf gap, respectively. The measured diameter of the 50% isodose line was 4.5
      and 5.7 mm for the 4 mm and 5 mm cones, respectively. The standard deviation of
      the parallel-plate chamber signal relative to a 10 cm * 10 cm field was less than
      0.4%. The relative signal changed 32% per millimeter change in leaf gap,
      indicating that the parallel-plate chamber is sensitive to changes in gap width.
      Conclusions: The virtual cone is an efficient technique for treatment of small
      spherical targets. Patient-specific quality assurance measurements will not be
      necessary in routine clinical use. Integration directly into the treatment
      planning system will make planning using this technique extremely efficient.

PMID- 30197944
TI  - Reasons for discontinuation of radiation therapy and effective countermeasures.

PMID- 30197945
TI  - Letter to the editor in response to Hopper et al, "Salvage image guided radiation
      therapy to the prostate after cryotherapy failure".

PMID- 30197946
TI  - Potential clinical applications of optical coherence tomography angiography in
      glaucoma.

PMID- 30197947
TI  - The prevalence of amblyopia in Iran: A systematic review.
AB  - Purpose: The aim of this study was to determine the prevalence of amblyopia in
      the population of Iran. Methods: This article is a systematic review. A
      comprehensive search was conducted in PubMed, Scopus, Science Direct, Ovid, Web
      of Science, SID, Magiran, with appropriate terms. Information related to the
      sample size and the prevalence of amblyopia was extracted and summarized in
      tables. Analysis was performed using STATA software. Results: From 551 articles
      that were originally extracted from the databases, 31 articles met the criteria
      for entering the review. These studies were conducted in different regions of
      Iran. The prevalence of amblyopia in different regions varied between 0.19 and
      3.69%. Study results were heterogeneous (I2 = 99.7%), and therefore, a meta
      analysis was not done. Conclusions: The prevalence of amblyopia in Iran is very
      different. In addition to conducting national screenings, it is necessary to
      report the incidence of amblyopia and its related factors in different parts of
      the country.

PMID- 30197949
TI  - Psychometric properties of the Glaucoma Quality of Life-15 questionnaire: Use of
      explanatory factor analysis.
AB  - Purpose: The purposes of this study were to validate the Persian translation of
      the Glaucoma Quality of Life-15 (GQL-15) questionnaire, evaluate its psychometric
      properties, and identify new composite items and item numbers. Methods: This
      cross-sectional study was conducted from August to November 2016, at the Glaucoma
      Clinic of the Ophthalmology Department at Shiraz University of Medical Sciences,
      Iran. One hundred ninety patients with glaucoma were enrolled. Habitual-corrected
      visual acuity (HCVA), intraocular pressure (IOP), slit-lamp biomicroscopy, fundus
      exam, and mean deviation (MD) of the visual field were recorded in the course of
      clinical examination by glaucoma professional. Psychometric properties, i.e. test
      retest reliability, internal consistency, content validity, and construct
      validity were evaluated with factor analysis. Based on the Disc Damage Likelihood
      Scale (DDLS), patients were stratified to mild, moderate, and severe disc damage.
      The association between the GQL-15 scores and disease severity (mild, moderate
      and severe) were evaluated by the analysis of variance (ANOVA). Results: Of 190
      eligible glaucoma patients, reliable clinical data were available for 140
      participants. Mean age [standard deviation (SD)] of the patients was 58.7 (13.3)
      years. Cronbach's alpha coefficient ranged from 0.74 to 0.91, and the correlation
      coefficient for total score was 0.53. The content validity ratio (CVR) was 0.91
      based on evaluations in expert panel. Exploratory factor analysis (EFA) based on
      eigenvalue higher than one identified two factors after varimax rotation for the
      GQL-15 which explained 66.5% of the total variance. Discriminant validity
      analysis disclosed statistically significant differences in mean quality of life
      scores between levels of disease severity. Conclusion: The Persian version of the
      GQL-15 is a reliable and valid questionnaire for use in glaucoma clinics as a
      complementary tool for evidence-based decision-making.

PMID- 30197950
TI  - Adjustment formulae to improve the correlation of white-to-white measurement with
      direct measurement of the ciliary sulcus diameter by ultrasound biomicroscopy.
AB  - Purpose: This study evaluates the correlation between horizontal white-to-white
      (WTW) distance using Caliper and Orbscan IIz with the ciliary sulcus diameter
      measured by high frequency ultrasound biomicroscopy (UBM) and presents an
      adjustment formula to improve the correlation. Methods: We measured horizontal
      sulcus-to-sulcus (STS) dimension of 273 right eyes of 273 high myopic patients
      with 35 MHz UBM and horizontal WTW using Orbscan IIz and Caliper. Mean WTW
      diameter, differences, and the correlation of measurement methods were evaluated.
      Results: The mean spherical equivalent was -8.79 +/- 4.87 diopters. Mean
      horizontal STS dimension with UBM was 12.13 +/- 0.45 mm (range, 10.81-13.42 mm).
      Mean WTW diameter in the Caliper method was 11.70 +/- 0.40 mm (range, 10.6-12.8
      mm) and 11.70 +/- 0.40 mm (range, 10.5-13.1 mm) in the Orbscan method. Mean
      difference of UBM STS and WTW with Caliper was 0.48 +/- 0.28 mm (range, -0.19 to
      1.37 mm). Mean difference of UBM STS diameter and Orbscan WTW was 0.38 +/- 0.31
      mm (range, -0.64 to 1.29 mm). The Pearson correlations of WTW diameter measured
      by Caliper and Orbscan with UBM's STS diameter were 0.778 and 0.773,
      respectively. This difference diminished after adjustment. The 95% limit of
      agreement was almost the same in Caliper and Orbscan (-0.07 to 1.03 compared with
      -0.23 to 0.99). Conclusion: There is a significant difference in measurements
      between STS diameter using UBM and WTW diameter utilizing Caliper and Orbscan.
      This difference diminished after our recommended adjustment.

PMID- 30197948
TI  - Ocular changes during pregnancy.
AB  - Purpose: To summarize available literature on physiologic and pathologic ocular
      changes during pregnancy. Methods: Narrative review of literature. Results:
      Ocular changes occur commonly during pregnancy. Although most of these are benign
      physiologic responses to the metabolic, hormonal, and immunologic modifications
      to adopt the gestational product, there is some serious pathology that may
      develop, exacerbate, or even resolve over the course of pregnancy which requires
      prompt diagnosis and management. The pathological eye conditions can be
      classified into preexisting pathologies and emerging ocular diseases. Regardless
      of the different mechanisms by which these ocular changes occur, the key point is
      the establishment of an effective perinatal screening program to monitor the new
      development or successive progression of these ocular abnormalities. Irrespective
      of the visual health status of the pregnant women, regular perinatal eye
      examination should be scheduled in order to assure continuous surveillance of
      healthy eyes. Treatment of pathologic ocular conditions or functionally
      disturbing benign changes relies on an appropriate patient selection.
      Conclusions: Discriminating pathological eye disease from physiologic ocular
      changes is important in order to establish an individualized treatment or
      preventive plan and constitutes the mainstay of obstetric ophthalmology. This
      individualized approach should always weigh the ocular benefits of treatment to
      the mother against the potential harms to the fetus.

PMID- 30197951
TI  - Multipoint assessment of demarcation line depth after standard and accelerated
      cross-linking in central and inferior keratoconus.
AB  - Purpose: To determine the changes in the depth of the demarcation line in the
      central to peripheral cornea following accelerated compared to standard corneal
      cross-linking (CXL). Methods: In this prospective, non-randomized study, 60 eyes
      with progressive keratoconus underwent accelerated or standard CXL (30 in each
      group). Anterior segment optical coherence tomography (AS-OCT) was done one month
      later by two independent masked examiners to measure the depth of the demarcation
      line in the central cornea and on peripheral rings. Results: The inter-examiner
      agreement (intra-class correlation coefficient) was >0.75 for all measured
      points, and average measurements were used in the analysis. The depth of the
      visualized demarcation line in the center was 223.4 +/- 67.4 MUm and 354.9 +/-
      79.0 MUm in the accelerated and standard groups, respectively (P < 0.001). The
      depth significantly decreased from the center to the 7 mm ring in both groups
      (all P < 0.05). This change was 7.7-26.1% and 2.2%-11.1% in the accelerated and
      standard groups, respectively. In the accelerated group, the demarcation line was
      deeper in the central cone sub-group compared to the inferior cone sub-group, but
      in the standard group, the demarcation line was deeper in the inferior cone sub
      group (all P < 0.05). Cases with an inferior cone showed greater inter-group
      differences in all studied points. Conclusions: The depth of the demarcation line
      with accelerated CXL is less than the standard protocol and decreases from the
      center towards the periphery. Demarcation lines are more homogenized with
      standard CXL. In cases with an inferior cone, demarcation line depth varies
      throughout the cornea.

PMID- 30197952
TI  - A contralateral eye study comparing characteristics of corneal endothelial cells
      in bilateral keratoconus patients with unilateral corneal Vogt's striae.
AB  - Purpose: The aim of this study was to analyze and compare corneal endothelial
      cell morphology and characteristics in bilateral keratoconus (KCN) patients with
      unilateral Vogt's striae. Methods: Fifty patients aged 20-38 years were recruited
      in this cross-sectional contralateral eye study. In this study, corneal
      endothelial cell parameters were evaluated in patients with bilateral KCN and
      unilateral Vogt's striae using the Topcon SP2000P specular microscope (Topcon,
      Tokyo, Japan). Results: In the current study, there were no significant
      differences in corneal endothelial cell parameters including endothelial cell
      density (ECD), hexagonal cell ratio (HEX), and coefficient of variance of cell
      size (CV) between the KCN groups with and without Vogt's striae, [(2968.34 +/-
      276.65 vs. 2980.05 +/- 253.30, P = 0.618), (51.88 +/- 13.57 vs. 53.24 +/- 9.31, P
      = 0.658), and (32.50 +/- 5.40 vs. 32.97 +/- 4.07, P = 0.467), respectively].
      Also, among study groups with and without Vogt's striae, ECD did not correlate
      with anterior chamber depth (ACD) [(P = 0.564, r = 0.09), (P = 0.219, r = -0.18),
      respectively], maximum keratometry (Kmax) [(P = 0.215, r = 0.18), (P = 0.898, r =
      0.02), respectively], and central corneal thickness (CCT) [(P = 0.989, r = 
      0.02), (P = 0.643, r = -0.07), respectively].Our results showed significant
      differences in corrected and uncorrected distance visual acuity (UDVA),
      cycloplegic refractive error components (calculated by vectorial analysis), CCT,
      and Kmax between two study groups (all P < 0.05) except for J45 (Jackson cross
      cylinder, axes at 45 and 135 degrees ) (P = 0.131). Conclusions: We were not able
      to find the statistically significant differences in ECD, HEX, and CV between KCN
      eyes with and without Vogt's striae. Despite clinical and tomographic results, it
      seems that Vogt's striae cannot cause deterioration in the corneal endothelial
      morphology.

PMID- 30197953
TI  - A novel PAX6 nonsense mutation identified in an Iranian family with various eye
      anomalies.
AB  - Purpose: The aim of this study was to detect the genetic defects in a large
      pedigree of affected individuals with various phenotypes of ocular anomalies
      including partial aniridia, congenital cataract, and nystagmus. Methods: The
      entire coding region of paired box gene 6 (PAX6) was amplified by polymerase
      chain reaction (PCR), sequenced, and compared with a GenBank database. Results: A
      novel mutation (c.1170 C > T; p.Gln297X) was found in the proband and all
      affected members. This nonsense mutation leads to PAX6 protein truncation.
      Conclusions: Our findings suggest that this novel mutation is most likely
      responsible for the pathogenesis of the congenital aniridia, cataract, and
      nystagmus in this pedigree. To the best of our knowledge, this is the first
      report of this mutation of PAX6 gene in a kindred pedigree with various ocular
      abnormalities.

PMID- 30197954
TI  - Pellet gun injury as a source of ocular trauma; a retrospective review of one
      hundred and eleven cases.
AB  - Purpose: To report the demographic data, treatment methods, and outcomes among
      patients with pellet gun eye injuries. Methods: This study was a retrospective
      review of all pellet gun eye injuries coming to Farabi Eye Hospital, a referral
      ocular trauma center in Iran, from February 2009 to November 2013. Patients'
      demographics, type of injury, choice of management, complications, and post
      treatment visual acuity were recorded. Results: One hundred eleven patients with
      a mean age of 25.7 +/- 15.6 years entered the study. The most common age group
      was younger adults (16-45 years old) (61.3%). The mean uncorrected visual acuity
      after treatment was 2.05 (20/2240) +/-1.5 logMAR. The most prevalent ocular zone
      was zone III (38.7%), and an intraocular foreign body was present in 97 patients
      (87.4%). Lid laceration and periocular tissue damage were present in 27 patients
      (24.3%). Lensectomy and vitrectomy were the most common treatment (31.5%). In
      most patients (87.4%), the injury was non-deliberate, and the most common time of
      hospitalization was the same day (45.0%). The only statistically significant
      indicator of post-treatment visual acuity was ocular trauma score (OTS) at
      admission (P < 0.001). At the end of follow-up, enucleation was performed for 20
      patients (18%), and thirty-six patients (32%) had no light perception (NLP) in
      vision. Conclusion: Pellet gun injuries were more common among young male
      patients, and the only statistically significant indicator of post-treatment
      visual acuity was OTS at admission.

PMID- 30197955
TI  - Role of combined phacoemulsification and intravitreal injection of bevacizumab in
      prevention of postoperative macular edema in non-proliferative diabetic
      retinopathy.
AB  - Purpose: To evaluate the role of combined phacoemulsification and intravitreal
      injection of bevacizumab in prevention of postoperative diabetic macular edema
      (DME) in patients with no diabetic retinopathy or non-proliferative diabetic
      retinopathy (NPDR) and without macular edema. Methods: In a prospective
      randomized clinical trial, 71 eyes from 71 diabetic patients with no diabetic
      retinopathy or mild NPDR and with central macular thickness (CMT) of less than
      300 MUm were enrolled and were randomized into two groups: combined
      phacoemulsification and intravitreal bevacizumab injection group and only
      phacoemulsification group. Our primary outcome measures included best corrected
      visual acuity (BCVA), CMT, and total macular volume (TMV) before and after (1
      month and 3 months) the cataract surgery. Results: The two groups did not show
      any significant difference in terms of baseline BCVA, age, CMT, stage of diabetic
      retinopathy. While the bevacizumab group showed lower CMT one month after the
      surgery compared to control group (267.3 +/- 31.8 and 293.6 +/- 53.7,
      respectively, P = 0.019), this difference did not remain significant 3 months
      after surgery (264.5 +/- 21.9 and 291.4 +/- 79.8, P = 0.089). The TMV and BCVA in
      the two groups showed no significant difference one month or 3 months after
      surgery. Considering our definition of post-cataract surgery diabetic macular
      edema (PME) in this study [CMT >300 MUm using spectral domain optical coherence
      tomography (SD-OCT)], there was no significant difference between the incidence
      of PME at 1 month and at 3 months after surgery. Conclusions: Although the
      intravitreal injection of bevacizumab during phacoemulsification would result in
      decreased macular thickness in patients with no diabetic retinopathy or NPDR and
      without macular edema in the early postoperative period, this effect would no
      longer persistent at 3 months. In addition, the BCVA and TMV showed no
      significant difference between the two groups at any time during follow-up
      period.

PMID- 30197956
TI  - The prevalence of refractive errors in 5-15 year-old population of two
      underserved rural areas of Iran.
AB  - Purpose: To determine the prevalence of hyperopia and myopia and their
      associations with age and gender in 5- to 15-year-old children in underserved
      rural areas in Iran. Methods: In this cross-sectional study, sampling was done
      using a multistage cluster sampling method from two underprivileged rural regions
      in Iran, and 3851 persons over 1 year old of age were invited to the study. After
      inviting the selected participants, examinations were conducted at a designated
      site in the selected villages. All participants underwent measurements of
      uncorrected and corrected visual acuity, manifest refraction, and a slit-lamp
      examination. Cycloplegic refraction was done by instilling cyclopentolate 1% eye
      drops in under 15-year-old participants. Results: Of the 3851 selected persons,
      3314 subjects participated (86.5%), and of these, 602 were in the 5-15 year age
      group. The prevalence of myopia and hyperopia in the studied children was 2.60%
      [95% confidence interval (CI): 1.10-4.10] and 4.00% (95% CI: 1.84-6.15),
      respectively. The prevalence of myopia in male and female children was 2.65% and
      2.55%, respectively (P = 0.951). The prevalence of hyperopia in male and female
      children was 2.83% and 5.25%, respectively (P = 0.130). The prevalence of myopia
      in the villages of southwest and north was 2.42% and 3.09%, respectively (P =
      0.618), and the prevalence of hyperopia was 4.71% and 2.10%, respectively (P =
      0.0056). Conclusion: The present report is a brief description of the status of
      refractive errors in children residing in underprivileged villages of two rural
      districts in Iran. As presented, the prevalence of myopia is not high, although
      the prevalence of hyperopia is in the mid-range compared to previous studies.

PMID- 30197957
TI  - Awareness and knowledge on eye donation among Allied Health Sciences, medical,
      and nursing students in Goa.
AB  - Purpose: To assess the awareness and knowledge on eye donation among students of
      Allied Health Sciences (AHS), medical, and nursing. Methods: A cross-sectional
      descriptive study was conducted using a standard predesigned and pretested closed
      ended structured questionnaire based on eye donation to obtain information about
      awareness and knowledge from AHS, medical, and nursing students of Goa. Results:
      Three hundred and forty participants participated in the study. The majority of
      the participants [97.9% (95% CI: 95.8-99.2)] were aware of the existence of eye
      donation. Mass media (62.9%) was the foremost source of information. However,
      only 145 [42.6% (95% CI: 37.3-48.1)] participants were willing to donate their
      eyes. AHS, medical, and nursing students stood apart significantly in their
      awareness and knowledge. Only 60 [17.6% (95% CI: 13.7-22.1)] participants were
      aware that the whole eye can be removed from the donor while 215 [63.2% (95% CI:
      57.9-68.4)] were wrongly aware that the cornea can be removed separately.
      Awareness about eye donation was not associated with willingness to donate eyes.
      Conclusions: Although awareness regarding eye donation was satisfactory, there
      was lack of willingness to donate eyes. There is a need to bridge the gap between
      eye bank and donors.

PMID- 30197958
TI  - Evaluation of rhegmatogenous retinal detachments using Optos ultrawide field
      fundus fluorescein angiography and comparison with ETDRS 7 field overlay.
AB  - Purpose: To evaluate the ultrawide field fundus fluorescein angiography (UWFA)
      characteristics of rhegmatogenous retinal detachments (RRDs) and compare the
      findings with an early treatment diabetic retinopathy study (ETDRS) 7 field
      (ETDRS7F) overlay. Methods: UWFA (Optos, PLC, Dunfermline, UK) was performed in
      10 eyes with macula-off RRDs in 9 patients. The findings of UWFA were compared
      with that of an overlay of standard ETDRS7F. Results: Vascular dilation,
      tortuosity of vessels, and blockage of choroidal fluorescence were noted in all
      eyes in both UWFA and ETDRS7F overlay. Other findings in UWFA and ETDRS7F
      included peripheral perivascular staining (10 versus 4 eyes), peripheral
      capillary nonperfusion (CNP) (9 eyes compared to none), vascular loop formation
      (7 eyes versus none), optic disc hyperfluorescence (5 eyes in both), petaloid
      leak at macula (2 eyes in both), and neovascularization elsewhere (3 eyes versus
      none). Conclusions: Peripheral perivascular staining and leak, CNP, and vascular
      tortuosity are common UWFA features of RRDs. Standard ETDRS7F missed peripheral
      CNP, peripheral vascular loops, and peripheral retinal new vessels in all eyes
      compared to UWFA in the current study.

PMID- 30197960
TI  - Successful surgical management of sixth nerve palsy by transposition of a
      previously snapped and retrieved inferior rectus muscle.
AB  - Purpose: To report a case of intraoperative rupture of inferior rectus muscle,
      which was retrieved and later successfully transposed for management of sixth
      nerve palsy. Methods: Case report. Results: A 36-year-old woman presented with
      traumatic right sixth nerve palsy and esotropia following a car accident five
      years earlier. During the originally planned vertical transposition surgery, the
      inferior rectus muscle snapped, but was retrieved and resutured to the sclera 3
      mm posterior to the original insertion. After a few months, the second attempt of
      transposition of vertical recti (including the previously snapped and reattached
      inferior rectus) was successful, and the patient achieved satisfactory
      postoperative alignment. Conclusions: Intraoperative rupture of an extraocular
      muscles is a rare and serious complication encountered during strabismus surgery.
      However, if successfully retrieved, this muscle has still the chance of future re
      operation.

PMID- 30197959
TI  - Conjunctivitis as a manifestation of Wegener's Granulomatosis.
AB  - Purpose: To report a case of prolonged conjunctivitis as the manifestation of
      Granulomatosis with polyangiitis (GPA). Methods: A 37-year-old man presented with
      prolonged conjunctivitis which had persisted for one month. He was taking
      medication for his conjunctivitis without any response. A slit-lamp examination
      revealed conjunctivitis and scleritis in the right eye. Conjunctivitis, 360
      degree peripheral corneal thinning, corneal perforation, and scleritis were seen
      in the left eye. Results: Emergency penetrating keratoplasty was performed to
      treat the patient's corneal perforation. After a consultation with the Internal
      Medicine Department, the patient was suspected of having GPA with positive
      cytoplasmic anti-neutrophil cytoplasmic antibodies (C-ANCA). Functional
      endoscopic sinus surgery was performed to treat right maxillary sinusitis, and a
      biopsy of the maxillary sinus mucosa was obtained. The pathology report showed
      granuloma and vasculitis with severe acute and chronic inflammation and few
      eosinophils; thus, the diagnosis was confirmed. Conclusion: Because prolonged
      conjunctivitis occurs only rarely in association with systemic disease,
      ophthalmologists should be aware of this potential, particularly in patients with
      GPA.

PMID- 30197961
TI  - The effect of bevacizumab before vitrectomy for diabetic tractional retinal
      detachment demonstrated on optical coherence tomography angiography.
AB  - Purpose: To demonstrate the effect of intravitreal bevacizumab (IVB) on the size
      and vascularity of the fibro-vascular complex with the optical coherence
      tomography angiography (OCTA) before pars plana vitrectomy (PPV). Methods:
      Observational case series of three eyes with active diabetic fibro-vascular
      complex and tractional retinal detachment (TRD) who underwent IVB (1.25 mg/0.05
      ml) two days before proceeding to PPV. OCTA was carried out prior to IVB, two
      days after IVB and six weeks after PPV. Results: OCTA showed a reduction in the
      size and calibre of the diabetic fibro-vascular complex two days after IVB in all
      the cases. Consequently, there was less traumatic dissection of the fibro
      vascular membranes during PPV and thus reduced chances of intraoperative and
      postoperative vitreous cavity bleeding. One case showed mild hemorrhage in the
      posterior vitreous on the second day post-injection which implies the increased
      traction caused by IVB. Conclusions: In this case series, we have used OCTA to
      demonstrate how IVB is highly effective in reducing the vascularity of diabetic
      fibro-vascular membranes. This finding also suggests that the use of IVB before
      PPV in the management of diabetic TRD could also be much shorter than the
      advocated standard practice of one week in most institutions.

PMID- 30197962
TI  - Corneal biomechanical parameters in pellucid marginal degeneration.

PMID- 30197964
TI  - The Placenta Effect: Risk Factors for Adverse Fetal Outcomes in Pregnant Dialysis
      Patients.

PMID- 30197966
TI  - Lower Mortality in Living Kidney Donors With ESRD Versus Matched Nondonors With
      ESRD.

PMID- 30197965
TI  - "Scanning" into the Future: The Promise of SOMAScan Technology for Kidney
      Disease.

PMID- 30197963
TI  - How the Interaction of Childhood Sexual Abuse and Gender Relates to HIV Risk
      Practices among Urban-Dwelling African Americans.
AB  - Purpose: Previous research has demonstrated that HIV risk practices often differ
      based on gender and on whether or not people experienced sexual abuse during
      their formative (i.e., childhood and adolescence) years. The interaction of these
      two factors, which is the focus of this paper, has received limited attention.
      Methods: Based on a model derived from Social Disorganization Theory and
      Syndemics Theory, interviews were conducted between 2009 and 2012 with 1,864
      African American adults residing in Atlanta, Georgia in 80 strategically-chosen
      consensus block groups. Results: Based on multiple regression and structural
      equation analyses, the interaction of sexual abuse and gender was found to be a
      significant predictor of involvement in (un)protected sex. The interaction of
      sexual abuse and gender also was related to condom use self-efficacy, which was
      one of the strongest factors underlying (un)protected sex. Conclusion: The
      relationship of sexual abuse history and gender is relevant in the understanding
      of HIV risk practices. The interaction of these factors with one another and with
      other relevant influences that shape people's HIV risk profiles is complex. The
      Syndemics Theory approach used to conceptualize the relationships among relevant
      variables in this study is an effective way of trying to understand and address
      HIV risk practices.

PMID- 30197967
TI  - Newer Point-of-Care Biosensors Are Expected to Permit Early Detection and Better
      Management of Acute and CKD.

PMID- 30197968
TI  - The Tragedy of Having ESRD in Mexico.

PMID- 30197969
TI  - Renal Outcomes of Antidiabetic Treatment Options for Type 2 Diabetes-A Proposed
      MARE Definition.
AB  - One of the most critical long-term complications of type 2 diabetes is
      nephropathy, currently termed diabetic kidney disease. Although the prevalence is
      increasing, renal outcomes are heterogeneously defined. Intensive glucose control
      is effective for the prevention of microvascular complications, including kidney
      disease. However, the impact of specific drugs on renal outcome measures such as
      the incidence of kidney disease, albuminuria, progression to end-stage kidney
      disease, or death of renal cause remains unclear. Comparison of agents or drug
      classes is impossible, as renal outcomes are inconsistently defined in trials.
      Recent publications include more stringent criteria, but use only composite
      endpoints, which can reveal significant results driven by a single surrogate
      marker but not clinical events of true relevance to patients. This review
      discusses renal outcomes related to antidiabetic agents for type 2 diabetes, in
      an attempt to determine the influence of specific drugs on the incidence of
      diabetic kidney disease and various renal outcomes. There are marked differences
      among the various agents, but direct comparisons are difficult due to
      heterogeneous measures. Statements from Kidney Disease Improving Global Outcomes
      (KDIGO) or European Renal Best Practice (ERBP) highlight that "standardized
      outcome reporting is key to achieving evidence-based guidance and improving
      clinical care for patients." Renal outcome studies including a well-defined,
      standardized core set of patient-relevant outcomes are needed. Here, we propose
      to define and establish major adverse renal events (MARE) as the outcome measure
      for future studies.

PMID- 30197971
TI  - Mortality in Living Kidney Donors With ESRD: A Propensity Score Analysis Using
      the United States Renal Data System.
AB  - Introduction: In recent years, data have emerged on the outcomes of living kidney
      donors who develop end-stage renal disease (ESRD). We aimed to evaluate mortality
      rates in kidney donors who had initiated dialysis compared with a propensity
      matched cohort of dialysis patients without previous kidney donation. Methods: We
      used the United States Renal Data System (USRDS) and abstracted 274 previous
      living kidney donors between 1995 and 2009. There were 609,398 individuals on
      dialysis without kidney donation. We used propensity score matching to identify
      258 donors and 258 nondonors. The time-dependent Cox proportional hazards model
      was used to compare survival between the 2 matched cohorts. Results: In the
      propensity score-matched cohort, mortality was lower in donors compared with
      nondonors (19% vs. 49%; P < 0.0001). The time-dependent Cox proportional hazards
      model demonstrated that donors had significantly lower mortality compared with
      nondonors 0 to 5 years since start of dialysis (hazard ratio [HR]: 0.17; 95%
      confidence interval [CI] 0.11-0.27; P < 0.0001) and with nondonors 5 to 10 years
      on dialysis (HR: 0.34; 95% CI: 0.19-0.63; P < 0.001). We were unable to estimate
      the difference between the 2 groups after 10 years on dialysis with any precision
      (HR: 0.51; 95% CI: 0.18-1.42; P = 0.20) due to the small sample size. Conclusion:
      We observed a lower mortality rate in living kidney donors with ESRD compared
      with matched nondonors. This data should guide clinicians in the informed consent
      process with prospective donors.

PMID- 30197970
TI  - Comparisons of Guidelines and Recommendations on Managing Antineutrophil
      Cytoplasmic Antibody-Associated Vasculitis.
AB  - Antineutrophil cytoplasmic antibodies-associated vasculitis (AAV) is associated
      with high morbidity or mortality, especially if not promptly diagnosed and
      treated. Many inroads have been made in the understanding of the pathophysiology
      that leads to exploration of novel therapies. Randomized controlled trials over
      the last 2 decades have better delineated and expanded therapeutic options and
      set the stage for an evidence-based approach. Since 2014, 4 scientific societies
      have systematically reviewed the existing data and have formulated evidence-based
      recommendations for the management of AAV. These recommendations cover diagnosis,
      remission induction and maintenance treatment, and prevention of long-term
      complications. This review is a comparative analysis of the recently published
      recommendations of the European League Against Rheumatism/European Renal
      Association-European Dialysis and Transplant Association, the British Society of
      Rheumatology, the Canadian Vasculitis Research Network, and the Brazilian Society
      of Rheumatology, and aims to determine common ground among them and highlights
      the differences among the recommendations.

PMID- 30197972
TI  - Limited Reliability of the Spot Urine Protein/Creatinine Ratio in the
      Longitudinal Evaluation of Patients With Lupus Nephritis.
AB  - Introduction: Cross-sectional studies document that the spot protein/creatinine
      ratio (PCR) is often an inaccurate estimate of proteinuria magnitude compared
      with the 24-hour PCR, which is the gold standard. However, the extent to which
      the inaccuracy of the spot PCR varies over time and between individuals has not
      previously been reported. We address these crucial questions using a unique
      database, an National Institutes of Health trial in which lupus nephritis (LN)
      patients (N = 103) provided spot PCR testing each month and 24-hour PCR testing
      every 3 months for up to 15 months after induction therapy. Methods: A gold
      standard proteinuria trend line was constructed for each patient by joining the
      points that represented the serial 24-hour PCR values of the patient. The spot
      PCR values of the patient were then plotted in relationship to the 24-hour PCR
      trend line. Using our previous work, which estimated the 95% confidence intervals
      for the 24-hour PCR at specific levels, we determined in each patient whether the
      spot PCR values were "reliable," "problematic," or "unreliable." The sequential
      spot PCR of the patients deviated widely and often from the 24-hour PCR trend
      line, to the extent that, if the spot PCR results were used in real time for
      clinical decision-making, it was likely management errors would occur. Results:
      Spot PCRs were reliable in 41%, problematic in 24%, and unreliable in 35% of
      patients. Those with unreliable spot PCRs could not be predicted and were more
      likely to respond poorly to treatment. Conclusion: The spot PCR should not be
      used for management of LN, and perhaps, other glomerulopathies.

PMID- 30197973
TI  - Inequality in Care and Differences in Outcome Following Stroke in People With
      ESRD.
AB  - Introduction: Stroke rate and mortality are greater in individuals with end-stage
      renal disease (ESRD) than in those without ESRD. We examined discrepancies in
      stroke care in ESRD patients and their influence on mortality. Methods: This is a
      national record linkage cohort study of hospitalized stroke individuals from 2005
      to 2013. Presentation, measures of care quality (admission to stroke unit,
      swallow assessment, antithrombotics, or thrombolysis use), and outcomes were
      compared in those with and without ESRD after propensity score matching (PSM). We
      examined the effect of being admitted to a stroke unit on survival using Kaplan
      Meier and Cox survival analyses. Results: A total of 8757 individuals with ESRD
      and 61,367 individuals with stroke were identified. ESRD patients (n =486)
      experienced stroke over 34,551.9 patient-years of follow-up; incidence rates were
      25.3 (dialysis) and 4.5 (kidney transplant)/1000 patient-years. After PSM,
      dialysis patients were less likely to be functionally independent (61.4% vs.
      77.7%; P < 0.0001) before stroke, less frequently admitted to stroke units (64.6%
      vs. 79.6%; P < 0.001), or to receive aspirin (75.3% vs. 83.2%; P = 0.01) than non
      ESRD stroke patients. There were no significant differences in management of
      kidney transplantation patients. Stroke with ESRD was associated with a higher
      death rate during admission (dialysis 22.9% vs.14.4%, P = 0.002; transplantation:
      19.6% vs. 9.3%; P = 0.034). Managing ESRD patients in a stroke unit was
      associated with a lower risk of death at follow-up (hazard ratio: 0.68; 95%
      confidence interval: 0.55-0.84). Conclusion: Stroke incidence is high in ESRD.
      Individuals on dialysis are functionally more dependent before stroke and less
      frequently receive optimal stroke care. After a stroke, death is more likely in
      ESRD patients. Acute stroke unit care may be associated with lower mortality.

PMID- 30197974
TI  - Risk Factors for Adverse Fetal Outcome in Hemodialysis Pregnant Women.
AB  - Introduction: Pregnancy in women on dialysis is associated with a higher risk of
      adverse events, and the best care for this population remains to be established.
      Methods: In this series, we aimed to identify factors associated with the risk of
      adverse fetal outcomes among 93 pregnancies in women on hemodialysis. Dialysis
      dose was initially assigned according to the presence of residual diuresis, body
      weight, and years on dialysis. Subsequent adjustments on dialysis dose were
      performed according to several parameters. Results: The overall successful
      delivery rate was 89.2%, with a dialysis regimen of 2.6 +/- 0.7 h/d, 15.4 +/- 4.0
      h/wk, and mean weekly standard urea Kt/V of 3.3 +/- 0.6. In the logistic models,
      preeclampsia, lupus, primigravida, and average midweek blood urea nitrogen (BUN)
      level were positively related to the risk of a composite outcome of perinatal
      death or extreme prematurity, whereas polyhydramnios was inversely related to it.
      In multivariable linear regression, preeclampsia, polyhydramnios, primigravida,
      average midweek BUN, and residual diuresis remained significantly and
      independently related to fetal weight, which is a surrogate marker of fetal
      outcome. An average midweek BUN of 35 mg/dl was the best value for discriminating
      the composite outcome, and BUN >=35 mg/dl was associated with a significant
      difference in a Kaplan-Meier curve (P = 0.01). Conclusion: Our results showed
      that a good fetal outcome could be reached and that preeclampsia, lupus,
      primigravida, residual diuresis, polyhydramnios, and hemodialysis dose were
      important variables associated with this outcome. In addition, we suggested that
      a midweek BUN <35 mg/dl might be used as a target for adjusting dialysis dose
      until hard data were generated.

PMID- 30197975
TI  - Lipodystrophy Increases the Risk of CKD Development in HIV-Positive Patients in
      Switzerland: The LIPOKID Study.
AB  - Introduction: Antiretroviral therapy has improved the life expectancy of patients
      living with HIV. However, lipodystrophy syndrome (LD) remains prevalent,
      affecting mostly patients treated with first-generation antiretroviral drugs.
      This syndrome is characterized by changes in body fat distribution with or
      without associated metabolic changes. Here, we studied whether clinically
      evaluated LD is independently associated with chronic kidney disease (CKD)
      development (sustained estimated glomerular filtration rate [eGFR] < 60 ml/min
      per 1.73 m2) in HIV-positive patients. Methods: We conducted a prospective cohort
      study (the LIPOKID Study) among all the patients from the Swiss HIV Cohort Study
      (SHCS) with an eGFR >60 ml/min per 1.73 m2 upon their entry into the cohort with
      more than 3 months of follow-up from January 2002 to August 2016. Cox regression
      models were used to estimate the association between LD and CKD development.
      Results: Among the 5384 patients included, 1341 (24.9%) developed LD during the
      follow-up. The mean follow-up time was 72.3 months (SD +/-48.4). In total, 252
      patients (4.7%) reached the primary endpoint after a median time of 51.3 months
      (+/-SD 39.9 months) from inclusion. A diagnosis of LD significantly increased the
      risk of an eGFR on univariate analysis (hazard ratio [HR] = 2.72; 95% confidence
      interval [95% CI] = 2.07-3.58; P < 0.001) and remained significantly higher after
      adjustment for known HIV and non-HIV risk factors for CKD (HR = 2.37; 95% CI =
      1.67-3.36; P < 0.001). The effect of LD on CKD was not mediated through the use
      of nephrotoxic antiretroviral drugs. Conclusion: Lipodystrophy syndrome is
      independently associated with CKD after adjustment for previously reported risk
      factors.

PMID- 30197976
TI  - Soluble Urokinase Plasminogen Activator Receptor (suPAR) and All-Cause and
      Cardiovascular Mortality in Diverse Hemodialysis Patients.
AB  - Introduction: The soluble receptor of urokinase plasminogen activator (suPAR) is
      an innate immunity/inflammation biomarker predicting cardiovascular (CV) and non
      CV events in various conditions, including type 2 diabetic patients on dialysis.
      However, the relationship between suPAR and clinical outcomes in the hemodialysis
      population at large has not been tested. Methods: We measured plasma suPAR levels
      (R&D enzyme-linked immunosorbent assay [ELISA]) in 1038 hemodialysis patients
      with a follow-up of 2.9 years (interquartile range = 1.7-4.2) who were enrolled
      in the PROGREDIRE study, a cohort study involving 35 dialysis units in 2 regions
      in Southern Italy. Results: suPAR was strongly (P < 0.001) and independently
      related to female gender (beta = -0.160), age (beta = 0.216), dialysis vintage
      (beta = 0.264), CV comorbidities (beta = 0.105), alkaline phosphatase (beta =
      0.136), albumin (beta = -0.147), and body mass index (BMI; beta = 0.174) (all P <
      0.006). In fully adjusted analyses, suPAR tertiles predicted the risk of all
      cause mortality (third tertile vs. first tertile hazard ratio (HR) = 1.91, 95%
      confidence interval (CI) = 1.47 - 2.48, P < 0.001), CV mortality (HR = 1.47, 95%
      CI = 1.03-2.09, P = 0.03), and non-CV mortality (HR = 1.94, 95% CI = 1.28-2.93, P
      = 0.002); these relationships were not modified by diabetes or other risk
      factors. suPAR added only modest prognostic risk discrimination and
      reclassification power for these outcomes to parsimonious models based on simple
      clinical variables. Conclusion: In conclusion, suPAR robustly predicted all-cause
      and both CV and non-CV mortality in a large unselected hemodialysis population.
      Intervention studies are needed to definitively test the hypothesis that suPAR is
      causally implicated in clinical outcomes in this population.

PMID- 30197977
TI  - Application of a Nanotechnology-Based, Point-of-Care Diagnostic Device in
      Diabetic Kidney Disease.
AB  - Introduction: Early detection of diabetes mellitus (DM) and diabetic kidney
      disease (DKD) is important for preventing end-stage renal failure and reducing
      cardiovascular complications. Availability of a validated point-of-care (PoC)
      device that can measure various DKD markers would be useful in this respect,
      especially in resource-poor parts of the world. Methods: We validated a novel
      nanotechnology-based multianalyte PoC device (minimally invasive and does not
      require trained medical personnel) against laboratory gold standard tests for the
      detection of 5 biomarkers related to management of DM and DKD. The prospective
      study was funded by an International Society of Nephrology American Nephrologists
      of Indian Origin grant in 2 phases: (i) proof of concept: random samples were
      tested for the analytes with the PoC device and correlated with the laboratory
      gold standard; and (ii) clinical validation in a well-characterized cohort of
      patients. A nonenzymatic- and nonantibody-based electrochemical PoC device for
      quantitative measurement of markers-glycosylated hemoglobin (HbA1c), hemoglobin,
      serum albumin, microalbuminuria, urine creatinine, and albumin-to-creatinine
      ratio-was developed and used in this study. The disposable strips were interfaced
      with a multipotentiostat hand-held PoC device (3.7-V rechargeable lithium
      battery, 5-inch touch screen, Bluetooth enabled) working in amperometry mode,
      which provided the results in <1 minute. Data were analyzed using linearity plots
      and Bland-Altman difference plot analysis. Results: A total of 4717 individuals
      were screened during the study (phase 1: 2576 and phase 2: 2141.) In phase 2,
      samples were tested in 529 subjects (346 females)-120 subjects with type 1 DM,
      255 subjects with type 2 DM, 54 subjects without DM, 400 subjects with stage 2
      chronic kidney disease, and 30 subjects with stage 3 chronic kidney disease.
      Conclusion: A nanotechnology-based PoC device for quantitative measurement of
      HbA1c, hemoglobin, serum albumin, microalbuminuria, and the urine albumin-to
      creatinine ratio was developed for detection of early DKD and showed excellent
      correlation between the device and laboratory results. This device has the
      potential for early detection of DM and/or DKD, especially in remote communities
      in underserved areas of the world where prevalence of diabetes is rapidly
      increasing.

PMID- 30197978
TI  - Extracorporeal Stromal Cell Therapy for Subjects With Dialysis-Dependent Acute
      Kidney Injury.
AB  - Introduction: The pathophysiology of acute kidney injury (AKI) involves damage to
      renal epithelial cells, podocytes, and vascular beds that manifests into a
      deranged, self-perpetuating immune response and peripheral organ dysfunction.
      Such an injury pattern requires a multifaceted therapeutic to alter the wound
      healing response systemically. Mesenchymal stromal cells (MSCs) are a unique
      source of secreted factors that can modulate an inflammatory response to acute
      organ injury and enhance the repair of injured tissue at the parenchymal and
      endothelial levels. This phase Ib/IIa clinical trial evaluates SBI-101, a
      combination product that administers MSCs extracorporeally to overcome
      pharmacokinetic barriers of MSC transplantation. SBI-101 contains allogeneic
      human MSCs inoculated into a hollow-fiber hemofilter for the treatment of
      patients with severe AKI who are receiving continuous renal replacement therapy
      (CRRT). SBI-101 therapy is designed to reprogram the molecular and cellular
      components of blood in patients with severe organ injury. Methods: This study is
      a prospective, multicenter, randomized, double-blind, sham-controlled, study of
      subjects with a clinical diagnosis of AKI who are receiving CRRT. Up to 32
      subjects may be enrolled to provide 24 evaluable subjects (as a per protocol
      population). Subjects will receive CRRT in tandem with a sham control (0 MSCs),
      or the low- (250 * 106 MSCs) or high-dose (750 * 106 MSCs) SBI-101 therapeutic.
      Results: The study will measure dose-dependent safety, renal efficacy, and
      exploratory biomarkers to characterize the pharmacokinetics and pharmacodynamics
      of SBI-101 in treated subjects. Conclusion: This first-in-human clinical trial
      will evaluate the safety and tolerability of SBI-101 in patients with AKI who
      require CRRT.

PMID- 30197979
TI  - Staphylococcal Infection-Related Glomerulonephritis With Cryoglobulinemic
      Features.
AB  - Introduction: Staphylococcal infection-related glomerulonephritis (GN) has been
      shown to represent a unique form of infection-related GN that contains IgA
      dominant deposits and is often seen concurrently with the bacterial infection.
      Biopsies commonly reveal an endocapillary proliferative and/or exudative or
      mesangial proliferative GN. Rare cases have been reported to show cryoglobulin
      like features, including hyaline pseudothrombi and wireloop deposits; however,
      detailed characterization of these cases is lacking. Methods: The pathology
      archives from the University of Utah and Sharp Memorial Hospital were reviewed
      from January 2016 to September 2017 in search of cases with GN containing IgA
      dominant deposits and features of cryoglobulinemia. Results: Of 1965 native
      kidney biopsies, 5 showed IgA-dominant GN with cryoglobulinemic features. All
      patients had active staphylococcal infections at the time of biopsy. All
      presented with acute kidney injury (serum creatinine range: 1.7-6 mg/dl), and all
      had proteinuria and hematuria. All biopsies showed exudative GN, and 4 biopsies
      had focal crescents. All had focally prominent hyaline pseudothrombi with or
      without wireloop deposits, and all showed co-dominant staining for IgA and C3 on
      immunofluorescence microscopy. Serologic testing for cryoglobulinemia was
      performed in 3 patients and was transiently positive in 1 patient. Four patients
      required hemodialysis at last follow-up, whereas 1 patient returned to baseline
      kidney function. Conclusion: IgA-dominant GN with cryoglobulinemic features is an
      uncommon but severe form of glomerular injury in patients with staphylococcal
      infections. Four of 5 patients had crescentic glomerular injuries, all of whom
      required hemodialysis at last follow-up. Patients with IgA-dominant GN with
      features of cryoglobulinemia should be evaluated for active staphylococcal
      infection.

PMID- 30197980
TI  - Prevalence and Risk Factors for CKD: A Comparison Between the Adult Populations
      in China and the United States.
AB  - Introduction: Chronic kidney disease (CKD) is an important noncommunicable
      disease globally. Overall prevalence of CKD and distribution of its stages differ
      between countries. We postulate that these differences may not only be due to
      variation in prevalence of risk factors but also their differential impact in
      different populations or settings. Methods: We used nationally representative
      data on the adult populations from both the United States (US; National Health
      and Nutrition Examination Survey [NHANES], 2009 to 2010, N = 5557) and China
      (China National Survey of CKD, 2009 to 2010, N = 46,949). Age, sex, central
      obesity, cardiovascular disease, diabetes, hypertension, and hyperuricemia were
      explored as candidate risk factors for CKD. The prevalence of CKD was calculated
      using survey weights. Results: The prevalence of decreased estimated glomerular
      filtration rate (eGFR), defined as eGFR < 60 ml/min per 1.73 m2, was 6.5% in the
      US versus 2.7% in China, whereas the prevalence of albuminuria (defined as urine
      albumin to creatinine ratio of >=30 mg/g) was 8.1% in the US versus 9.5% in
      China. The distribution of eGFR categories differed between the countries (P <
      0.001). Stronger associations of diabetes with both indicators were seen in the
      US participants, whereas stronger associations of male sex with both indicators
      and of hypertension with albuminuria were observed in the Chinese participants (P
      < 0.05). After multivariable adjustment, a 65% change in prevalence difference
      for decreased eGFR was seen between China and the US. Conclusion: People in China
      and the US share many common risk factors for CKD, but differences in prevalence
      and the potential impact of these risk factors for CKD were observed.

PMID- 30197981
TI  - The Circular RNA ciRs-126 Predicts Survival in Critically Ill Patients With Acute
      Kidney Injury.
AB  - Introduction: Circular RNAs (circRNAs) have recently been described as novel
      noncoding regulators of gene expression. They might have an impact on microRNA
      expression by their sponging activity. The detectability in blood of these RNA
      transcripts has been demonstrated in patients with cancer and cardiovascular
      disease. We tested the hypothesis that circulating circRNAs in blood of
      critically ill patients with acute kidney injury (AKI) at inception of renal
      replacement therapy may also be dysregulated and associated with patient
      survival. Methods: We performed a global circRNA expression analysis using RNA
      isolated from blood of patients with AKI as well as controls. This global screen
      revealed several dysregulated circRNAs in patients with AKI. Most highly
      increased circRNA-array-based transcripts as well as expression of the circRNA
      target miR-126-5p were confirmed in blood of 109 patients with AKI, 30 age
      matched healthy controls, 25 critically ill non-AKI patients, and 20 patients on
      maintenance hemodialysis by quantitative real-time polymerase chain reaction.
      Results: Circulating concentrations of 3 novel circRNAs were amplified in blood
      of patients with AKI and in controls. Circular RNA sponge of miR-126 (or ciRs
      126) was most highly altered compared to healthy controls and disease controls
      (fold change of 52.1). ciRs-126 was shown to bioinformatically sponge miR-126-5p,
      which was found to be highly suppressed in AKI patients and hypoxic endothelial
      cells. Cox regression and Kaplan-Meier curve analysis revealed ciRs-126 as an
      independent predictor of 28-day survival (P < 0.01). Conclusion: Circulating
      concentrations of circRNAs in patients with AKI are detectable. ciRs-126 may
      potentially sponge miR-126-5p and acts as a predictor of mortality in this
      patient cohort.

PMID- 30197982
TI  - Cobalamin C Deficiency Induces a Typical Histopathological Pattern of Renal
      Arteriolar and Glomerular Thrombotic Microangiopathy.
AB  - Introduction: Cobalamin C (cblC) deficiency is the most common inborn error of
      vitamin B12 metabolism. Renal failure attributed to thrombotic microangiopathy
      (TMA) has occasionally been described in the late-onset presentation of cblC
      deficiency, but kidney lesions associated with cblC deficiency remain poorly
      defined. This study aims to describe the characteristics of kidney disease in
      cblC deficiency, and to provide a comparative histological analysis with cblC
      independent renal TMA. Methods: We performed a multicenter retrospective study
      including 7 patients with cblC deficiency and 16 matched controls with cblC
      independent TMA. The patients included were aged 6 to 26 years at the time of the
      first manifestations. All patients presented with acute renal failure,
      proteinuria, and hemolysis; 5 patients required dialysis. Results: The
      histological study revealed arteriolar and glomerular TMA in all patients. After
      comparison with the cblC-independent TMA control group, a vacuolated aspect of
      the glomerular basement membrane and the intensity of glomerular capillary wall
      IgM deposits were more present in cblC deficiency patients than in controls. Six
      patients were treated with hydroxycobalamin. All of them improved, with
      disappearance of hemolysis, and 3 of the 4 patients requiring renal replacement
      therapy were weaned off dialysis. Conclusion: This study provides a precise
      description of kidney pathology in cblC deficiency. Due to major therapeutic
      implications, we suggest that patients with renal TMA be screened for cblC
      deficiency regardless of age, particularly when the kidney biopsy provides
      evidence of long-lasting TMA, including a vacuolated aspect of the glomerular
      basement membrane and glomerular capillary wall IgM deposition.

PMID- 30197983
TI  - Secondary Response to Chronic Respiratory Acidosis in Humans: A Prospective
      Study.
AB  - Introduction: The magnitude of the secondary response to chronic respiratory
      acidosis, that is, change in plasma bicarbonate concentration ([HCO3-]) per mm Hg
      change in arterial carbon dioxide tension (PaCO2), remains uncertain.
      Retrospective observations yielded Delta[HCO3-]/DeltaPaCO2 slopes of 0.35 to 0.51
      mEq/l per mm Hg, but all studies have methodologic flaws. Methods: We studied
      prospectively 28 stable outpatients with steady-state chronic hypercapnia.
      Patients did not have other disorders and were not taking medications that could
      affect acid-base status. We obtained 2 measurements of arterial blood gases and
      plasma chemistries within a 10-day period. Results: Steady-state PaCO2 ranged
      from 44.2 to 68.8 mm Hg. For the entire cohort, mean (+/- SD) steady-state plasma
      acid-base values were as follows: PaCO2, 52.8 +/- 6.0 mm Hg; [HCO3-], 29.9 +/-
      3.0 mEq/l, and pH, 7.37 +/- 0.02. Least-squares regression for steady-state [HCO3
      ] versus PaCO2 had a slope of 0.476 mEq/l per mm Hg (95% CI = 0.414-0.538, P <
      0.01; r = 0.95) and that for steady-state pH versus PaCO2 had a slope of -0.0012
      units per mm Hg (95% CI = -0.0021 to -0.0003, P = 0.01; r = -0.47). These data
      allowed estimation of the 95% prediction intervals for plasma [HCO3-] and pH at
      different levels of PaCO2 applicable to patients with steady-state chronic
      hypercapnia. Conclusion: In steady-state chronic hypercapnia up to 70 mm Hg, the
      Delta[HCO3-]/DeltaPaCO2 slope equaled 0.48 mEq/l per mm Hg, sufficient to
      maintain systemic acidity between the mid-normal range and mild acidemia. The
      estimated 95% prediction intervals enable differentiation between simple chronic
      respiratory acidosis and hypercapnia coexisting with additional acid-base
      disorders.

PMID- 30197984
TI  - Mortality in Patients With Chronic Renal Disease Without Health Insurance in
      Mexico: Opportunities for a National Renal Health Policy.
AB  - Introduction: Despite a systematic increase in the coverage of patients with end
      stage renal disease (ESRD) who have received dialytic therapies and
      transplantation over the past 2 decades, the Mexican health system currently
      still does not have a program to provide full coverage of ESRD. Our aim was to
      analyze mortality in patients with ESRD without health insurance. Methods: This
      was a prospective cohort study of 850 patients with advanced chronic kidney
      disease (CKD). Risk factors associated with death were calculated using a Cox's
      proportional hazards model. We used the statistical package SPSS version 22.0 for
      data analysis. Results: The mean age of patients was 44.8 +/- 17.2 years old. At
      the time of hospital admission, 87.6% of the population did not have a social
      security program to cover the cost of renal replacement treatment, and 91.3% of
      families had an income below US$300 per month. During the 3 years of the study,
      28.8% of the cohort patients were enrolled in 1 of Mexico's social security
      programs. The 3-year mortality rate was of 56.7% among patients without access to
      health insurance, in contrast to 38.2% of patients who had access to a social
      security program that provided access to renal replacement therapy (P < 0.001).
      Risk factor analysis revealed that not having health insurance increased
      mortality (risk ratio: 2.64, 95% confidence intervals: 1.84-3.79; P = 0.001).
      Conclusion: Mexico needs a coordinated National Kidney Health and Treatment
      Program. A program of this nature should provide the basis for an appropriate
      educational and intervention strategy for early detection, prevention, and
      treatment of patients with advanced chronic kidney disease.

PMID- 30197985
TI  - Urinary Tubular Injury Biomarkers Are Associated With ESRD and Death in the
      REGARDS Study.
AB  - Introduction: Urinary neutrophil gelatinase-associated lipocalin (uNGAL) and
      urinary kidney injury molecule-1 (uKIM-1) are established markers of subclinical
      acute kidney injury. In persons with reduced estimated glomerular filtration rate
      (eGFR) and albuminuria who are at high risk for end-stage renal disease (ESRD)
      and death, the associations of these urinary markers with incident ESRD or death
      is an area of active investigation. Methods: Among 1472 black and white
      participants from the REasons for Geographic and Racial Differences in Stroke
      (REGARDS) study with eGFR <=60 ml/min per 1.73 m2 (Chronic Kidney Disease
      Epidemiology Collaboration [CKD-EPI] cystatin, 2012) and albumin-to-creatinine
      ratio (ACR) >=30 mg/g, we evaluated the associations of baseline uNGAL and uKIM-1
      with progression to ESRD and all-cause death. Cox models were sequentially
      adjusted for urinary creatinine, traditional risk factors, C-reactive protein,
      ACR, and eGFR. Results: There were 257 ESRD events and 819 deaths over a median
      follow-up of 5.7 and 6.5 years, respectively. In demographic adjusted models,
      higher levels of uNGAL were associated with increased risk of ESRD and death, but
      these associations were attenuated in fully adjusted models including baseline
      eGFR for both ESRD (hazard ratio [HR] = 1.06 per doubling, 95% confidence
      interval [CI] 0.98-1.14) and death (HR = 1.04, 95% CI = 1.00-1.08). Higher levels
      of uKIM-1 were associated with increased risk of ESRD and death in demographic
      adjusted models, and although attenuated in fully adjusted models, remained
      statistically significant for both ESRD (HR = 1.24 per doubling, 95% CI = 1.08
      1.42) and death (HR = 1.10, 95% CI =1.03-1.19). Conclusion: In this cohort of
      high-risk patients with baseline eGFR <=60 ml/min per 1.73 m2 and albuminuria,
      renal tubular injury is associated with higher mortality and progression to ESRD.
      Further studies are necessary to investigate the mechanism underlying this
      increased risk.

PMID- 30197986
TI  - Apolipoprotein CII Amyloidosis Associated With p.Lys41Thr Mutation.
AB  - Introduction: Apolipoprotein CII amyloidosis (AApoCII) is a rare form of
      amyloidosis. Here, we report a novel mutation associated with AApoCII amyloidosis
      in 5 patients and describe their clinical, renal biopsy, and mass spectrometry
      findings. Methods: Five patients with renal AApoCII p.Lys41Thr amyloidosis were
      identified from our amyloid mass spectrometry cohort. Clinical features, kidney
      biopsy, and mass spectrometry findings were analyzed in this rare type of
      amyloidosis. Results: The patients were older adults (mean age of 71.6 years at
      diagnosis), presented with nephrotic-range proteinuria, and often had declining
      renal function. All renal biopsy specimens showed massive mesangial nodules
      composed of weakly eosinophilic, periodic acid-Schiff negative, Congo red
      positive amyloid deposits. There were no interstitial, vascular, or medullary
      deposits. In all cases, immunofluorescence studies were negative for Igs and
      electron microscopy showed amyloid fibrils. Proteomic analysis of Congo red
      positive amyloid deposits detected large amounts of apolipoprotein CII (APOC2)
      protein. We also detected APOC2 p.Lys41Thr mutant protein in amyloid deposits of
      all patients. DNA sequencing in 1 patient confirmed the presence of the mutation.
      Both mutant and wild-type forms of APOC2 were detected in amyloid deposits of all
      patients. Molecular dynamic simulations showed the variant mediating a collapse
      of the native structure of APOC2, thereby destabilizing the protein. Conclusion:
      We propose that AApoCII p.Lys41Thr amyloidosis is a new form of amyloidosis seen
      in elderly individuals, histologically exhibiting massive glomerular involvement,
      leading to nephrotic-range proteinuria and progressive chronic kidney disease.

PMID- 30197988
TI  - Antenatally Diagnosed ADPKD.

PMID- 30197987
TI  - Aptamer-Based Proteomics Identifies Mortality-Associated Serum Biomarkers in
      Dialysis-Dependent AKI Patients.
AB  - Introduction: Currently, no effective therapies exist to reduce the high
      mortality associated with dialysis-dependent acute kidney injury (AKI-D). Serum
      biomarkers may be useful in understanding the pathophysiological processes
      involved with AKI and the severity of injury, and point to novel therapeutic
      targets. Methods: Study day 1 serum samples from 100 patients and day 8 samples
      from 107 patients enrolled in the Veteran's Affairs/National Institutes of Health
      Acute Renal Failure Trial Network study were analyzed by the slow off-rate
      modified aptamers scan proteomic platform to profile 1305 proteins in each
      sample. Patients in each cohort were classified into tertiles based on baseline
      biomarker measurements. Cox regression analyses were performed to examine the
      relationships between serum levels of each biomarker and mortality. Results:
      Changes in the serum levels of 54 proteins, 33 of which increased and 21 of which
      decreased, were detected when comparing samples of patients who died in the first
      8 days versus patients who survived >8 days. Among the 33 proteins that
      increased, higher serum levels of fibroblast growth factor-23 (FGF23), tissue
      plasminogen activator (tPA), neutrophil collagenase (matrix metalloproteinase-8),
      and soluble urokinase plasminogen activator receptor, when stratified by
      tertiles, were associated with higher mortality. The association with mortality
      persisted for each of these proteins after adjusting for other potential risk
      factors, including age, sex, cardiovascular sequential organ failure assessment
      score, congestive heart failure, and presence of diabetes. Upper tertile levels
      of FGF23, tPA, and interleukin-6 on day 8 were associated with increased
      mortality; however, FGF23 barely lost significance after multivariable
      adjustment. Conclusions: Our results underscore an emerging proteomics tool
      capable of identifying low-abundance serum proteins important not only in the
      pathogenesis of AKI-D, but which is also helpful in discriminating AKI-D patients
      with high mortality.

PMID- 30197989
TI  - The Role of Oxidative Stress and Inflammation in Acute Oxalate Nephropathy
      Associated With Ethylene Glycol Intoxication.

PMID- 30197991
TI  - Reversal of Dialysis-Dependent Anti-Glomerular Basement Membrane Disease Using
      Plasma Exchange, Glucocorticosteroids, and Rituximab.

PMID- 30197990
TI  - CFHR5 Nephropathy in a Greek-Cypriot Australian Family: Ancestry-Informed
      Precision Medicine.

PMID- 30197992
TI  - Bilateral Renal Infarctions During the Use of Sumatriptan.

PMID- 30197993
TI  - Ibuprofen Abuse-A Case of Rhabdomyolysis, Hypokalemia, and Hypophosphatemia With
      Drug-Induced Mixed Renal Tubular Acidosis.

PMID- 30197994
TI  - Highly Potent 2-Oxoester Inhibitors of Cytosolic Phospholipase A2 (GIVA cPLA2).
AB  - Cytosolic phospholipase A2 (GIVA cPLA2) has attracted great interest as a
      medicinal target because it initiates the eicosanoid cascade and is involved in a
      number of inflammatory diseases. As a consequence, the development of potent
      synthetic inhibitors is of great importance. We have developed highly potent 2
      oxoester inhibitors of GIVA cPLA2 presenting XI(50) values between 0.000019 and
      0.000066. We demonstrate that the 2-oxoester functionality is essential for in
      vitro inhibitory activity, making these inhibitors useful research reagents.
      However, their high reactivity results in rapid degradation of the inhibitors in
      human plasma, limiting their pharmaceutical utility without further modification.

PMID- 30197995
TI  - Organometallic, Nonclassical Surfactant with Gemini Design Comprising pi
      Conjugated Constituents Ready for Modification.
AB  - Surfactants are functional molecules comprising a water-compatible head group and
      a hydrophobic tail. One of their features is the formation of self-assembled
      structures in contact with water, for instance, micelles, vesicles, or lyotropic
      liquid crystals. One way to increase the functionality of surfactants is to
      implement moieties containing transition-metal species. Ferrocene-based
      surfactants represent an excellent example because of the distinguished redox
      features. In most existing ferrocene-based amphiphiles, an alkyl chain is
      classically used as the hydrophobic tail. We report the synthesis and properties
      of 1-triisopropylsilylethynyl-1'-trimethylammoniummethylferrocene (FcNMe3TIPS).
      In FcNMe3TIPS, ferrocene is part of the head group (Gemini design) but is also
      attached to a (protected) pi-conjugated ethynyl group. Although this architecture
      differs from that of classical amphiphiles and those of other ferrocene-based
      amphiphiles, the compound shows marked surfactant properties comparable to those
      of lipids, exhibiting a very low value of critical aggregation concentration in
      water (cac = 0.03 mM). It forms classical micelles only in a very narrow
      concentration range, which then convert into monolayer vesicles. Unlike classical
      surfactants, aggregates already form at a very low concentration, far beneath
      that required for the formation of a monolayer at the air-water interface. At
      even higher concentration, FcNMe3TIPS forms lyotropic liquid crystals, not only
      in contact with water, but also in a variety of organic solvents. As an
      additional intriguing feature, FcNMe3TIPS is amenable to a range of further
      modification reactions. The TIPS group is easily cleaved, and the resulting
      ethynyl function can be used to construct heterobimetallic platinum-ferrocene
      conjugates with trans-Pt(PEt3)2X (X = Cl, I) complex entities, leading to a
      heterobimetallic surfactant. We also found that the benzylic alpha-position of
      FcNMe3TIPS is rather reactive and that the attached ammonium group can be
      exchanged by other substituents (e.g., -CN), which offers additional
      opportunities for further functionalization. Although FcNMe3TIPS is reversibly
      oxidized in voltammetric and UV-vis spectroelectrochemical experiments, the high
      reactivity at the alpha-position is also responsible for the instability of the
      corresponding ferrocenium ion, leading to a polymerization reaction.

PMID- 30197997
TI  - Isoxazolopyrimidine-Based Inhibitors of Plasmodium falciparum Dihydroorotate
      Dehydrogenase with Antimalarial Activity.
AB  - Malaria kills nearly 0.5 million people yearly and impacts the lives of those
      living in over 90 countries where it is endemic. The current treatment programs
      are threatened by increasing drug resistance. Dihydroorotate dehydrogenase
      (DHODH) is now clinically validated as a target for antimalarial drug discovery
      as a triazolopyrimidine class inhibitor (DSM265) is currently undergoing clinical
      development. We discovered a related isoxazolopyrimidine series in a phenotypic
      screen, later determining that it targeted DHODH. To determine if the
      isoxazolopyrimidines could yield a drug candidate, we initiated hit-to-lead
      medicinal chemistry. Several potent analogues were identified, including a
      compound that showed in vivo antimalarial activity. The isoxazolopyrimidines were
      more rapidly metabolized than their triazolopyrimidine counterparts, and the
      pharmacokinetic data were not consistent with the goal of a single-dose treatment
      for malaria.

PMID- 30197998
TI  - Reduced Graphene Oxide as a Monolithic Multifunctional Conductive Binder for
      Activated Carbon Supercapacitors.
AB  - Using reduced graphene oxide (r-GO) as a multifunctional conductive binder, a
      simple, cost-effective, and environmentally friendly approach is developed to
      fabricate activated carbon/reduced graphene oxide (AC/r-GO) composite electrodes
      for supercapacitors with outstanding performance. In such a composite, r-GO
      provides several much needed critical functions: r-GO not only serves as the
      binder material improving the AC particle/particle cohesion and electrode
      film/substrate adhesion but also improves the electrical conductivity of the
      composite and provides additional surfaces for ion adsorption. Furthermore,
      during electrode fabrication, initial GO precursor functions as an effective
      dispersant for AC, resulting in a stable electrode material slurry. Employing
      characterization by advanced microscopy techniques, we show that AC and r-GO
      assemble into an interconnected network structure, resulting in a composite with
      high specific capacitance, excellent rate capability, and long cycling life
      stability. Such high-performance electrodes coupled with their relatively simple,
      scalable, and low-cost fabrication process thereby provide a clear pathway toward
      large-scale implementation of supercapacitors.

PMID- 30197996
TI  - Multifunctional Nanosystem for Targeted and Controlled Delivery of Multiple
      Chemotherapeutic Agents for the Treatment of Drug-Resistant Breast Cancer.
AB  - By targeting CD44 receptors, inhibiting multidrug resistance (MDR), controlling
      drug release, and synergistically inhibiting tumor growth, a multilayered
      nanosystem was developed to serve as a multifunctional platform for the treatment
      of drug-resistant breast cancers. The multilayer nanosystem is composed of a
      poly(lactic-co-glycolic acid) core, a liposome second layer, and a chitosan third
      layer. The chitosan-multilayered nanoparticles (Ch-MLNPs) can co-deliver three
      chemotherapeutic agents: doxorubicin (DOX), paclitaxel (PTX), and silybin. The
      three drugs are released from the multilayered NPs in a controlled and sequential
      manner upon internalization and localization in the cellular endosomes. The
      presence of a chitosan layer allows the nanosystem to target a well-characterized
      MDR breast cancer biomarker, the CD44s receptor. In vitro cytotoxicity study
      showed that the nanosystem loaded with triple drugs, DOX-PTX-silybin, resulted in
      better antitumor efficacy than the single-drug or dual-drug nano-formulations.
      Likely attributed to the MDR-inhibition effect of silybin, the co-delivered DOX
      and PTX exhibited a better synergistic effect on MDR breast cancer cells than on
      non-MDR breast cancer cells. The in vivo study also showed that the multilayered
      nanosystem promoted MDR inhibition and synergy between chemotherapeutic agents,
      leading to significant tumor reduction in a xenograft animal model. Ch-MLNPs
      reduced the tumor volume by fivefold compared to that of the control group
      without causing overt cytotoxicity.

PMID- 30197999
TI  - Imaging pH Dynamics Simultaneously in Two Cellular Compartments Using a
      Ratiometric pH-Sensitive Mutant of mCherry.
AB  - The regulation of pH is essential for proper organelle function, and organelle
      specific changes in pH often reflect the dynamics of physiological signaling and
      metabolism. For example, mitochondrial energy production depends on the proton
      gradient maintained between the alkaline mitochondrial matrix and neutral
      cytosol. However, we still lack a quantitative understanding of how pH dynamics
      are coupled between compartments and how pH gradients are regulated at organelle
      boundaries. Genetically encoded pH sensors are well suited to address this
      problem because they can be targeted to specific subcellular locations and they
      facilitate live, single-cell analysis. However, most of these pH sensors are
      derivatives of green and yellow fluorescent proteins that are not spectrally
      compatible for dual-compartment imaging. Therefore, there is a need for
      ratiometric red fluorescent protein pH sensors that enable quantitative
      multicolor imaging of spatially resolved pH dynamics. In this work, we
      demonstrate that the I158E/Q160A mutant of the red fluorescent protein mCherry is
      an effective ratiometric pH sensor. It has a pKa of 7.3 and a greater than 3-fold
      change in ratio signal. To demonstrate its utility in cells, we measured activity
      and metabolism-dependent pH dynamics in cultured primary neurons and
      neuroblastoma cells. Furthermore, we were able to image pH changes simultaneously
      in the cytosol and mitochondria by using the mCherryEA mutant together with the
      green fluorescent pH sensor, ratiometric-pHluorin. Our results demonstrate the
      feasibility of studying interorganelle pH dynamics in live cells over time and
      the broad applicability of these sensors in studying the role of pH regulation in
      metabolism and signaling.

PMID- 30198001
TI  - Rapid Screen of Potential i-Motif Forming Sequences in DNA Repair Gene Promoters.
AB  - We have studied the in vitro stability of 25 potential i-motif-forming DNA
      sequences found within the promoter regions of 18 different human DNA repair
      genes. Three widely available methods of characterization were used to rapidly
      assess i-motif folding and stability and comprise a simple screen for preliminary
      identification of physiologically relevant i-motif forming sequences. Four highly
      pH-stable candidate sequences were identified exhibiting pH transitions (pH at
      which 50% of the oligodeoxynucleotides in solution are folded) at or above pH
      6.6, thermal melting temperatures above 37  degrees C and isothermal UV
      difference spectra characteristic of 2'-deoxycytidine imino-nitrogen protonation.
      These newly identified i-motif forming sequences could represent novel targets
      for understanding and modulating human DNA repair gene expression.

PMID- 30198002
TI  - Optical Optimization of the TiO2 Mesoporous Layer in Perovskite Solar Cells by
      the Addition of SiO2 Nanoparticles.
AB  - In this work, SiO2 nanoparticles (NPs) were integrated into the mesoporous TiO2
      layer of a perovskite solar cell to investigate their effect on cell performance.
      Different concentrations of SiO2/ethanol have been combined in TiO2/ethanol to
      prepare pastes for the fabrication of the mesoporous layer with which perovskite
      solar cells have been fabricated. Addition of SiO2 NPs of 50 and 100 nm sizes
      produces an enhancement of cell performance mainly because of an improvement of
      the photocurrent. This increment is in good agreement with the theoretical
      predictions based on light scattering induced by dielectric SiO2 NPs. The samples
      using modified scaffolds with NPs also present a significant lower current
      potential hysteresis indicating that NP incorporation also affects the ion
      accumulation at the perovskite interface, providing an additional beneficial
      effect. The results stress the importance of the appropriated management of the
      optical properties on further optimization of perovskite solar cell technology.

PMID- 30198000
TI  - Lipid Extraction by alpha-Synuclein Generates Semi-Transmembrane Defects and
      Lipoprotein Nanoparticles.
AB  - Modulations of synaptic membranes play an essential role in the physiological and
      pathological functions of the presynaptic protein alpha-synuclein (alphaSyn).
      Here we used solution atomic force microscopy (AFM) and electron paramagnetic
      resonance (EPR) spectroscopy to investigate membrane modulations caused by
      alphaSyn. We used several lipid bilayers to explore how different lipid species
      may regulate alphaSyn-membrane interactions. We found that at a protein-to-lipid
      ratio of ~1/9, alphaSyn perturbed lipid bilayers by generating semi-transmembrane
      defects that only span one leaflet. In addition, alphaSyn coaggregates with lipid
      molecules to produce ~10 nm-sized lipoprotein nanoparticles. The obtained AFM
      data are consistent with the apolipoprotein characteristic of alphaSyn. The role
      of anionic lipids was elucidated by comparing results from zwitterionic and
      anionic lipid bilayers. Specifically, our AFM measurements showed that anionic
      bilayers had a larger tendency of forming bilayer defects; similarly, our EPR
      measurements revealed that anionic bilayers exhibited more substantial changes in
      lipid chain mobility and bilayer polarity. We also studied the effect of
      cholesterol. We found that cholesterol increased the capability of alphaSyn in
      inducing bilayer defects and altering lipid chain mobility and bilayer polarity.
      These data can be explained by an increase in the lipid headgroup-headgroup
      spacing and/or specific cholesterol-alphaSyn interactions. Interestingly, we
      found an inhibitory effect of the cone-shaped phosphatidylethanolamine lipids on
      alphaSyn-induced bilayer remodeling. We explained our data by considering
      interlipid hydrogen-bonding that can stabilize bilayer organization and suppress
      lipid extraction. Our results of lipid-dependent membrane modulations are likely
      relevant to alphaSyn functioning.

PMID- 30198003
TI  - Quantum Dot-Based Probes for Labeling and Imaging of Cells that Express Matrix
      Metalloproteinases.
AB  - The practical synthesis of novel multivalent fluorescent quantum-dot-based probes
      to target cellular matrix metalloproteinases (MMPs) (MT-MMPs) is reported. We
      show that these probes, which are decorated with a nanomolar water-soluble MMP
      inhibitor, can be used to label preferentially the surface of cancer cells that
      are known to express MMPs while no binding was observed on cells that do not.

PMID- 30198004
TI  - Altering Nitrogen Heterocycles of AZD2461 Affords High Affinity Poly(ADP-ribose)
      Polymerase-1 Inhibitors with Decreased P-Glycoprotein Interactions.
AB  - Poly(ADP-ribose) polymerase inhibitors (PARPi) are targeted therapeutics with
      enhanced selectivity and cytotoxicity in BRCA1/2 mutant cancer cells. AZD2461, a
      congener of FDA approved olaparib, is a potent PARPi with high affinity for PARP
      1 and nonsubstrate for P-glycoprotein (P-gp), an attractive characteristic for
      cancer therapeutics. Analogues of AZD2461 were synthesized and profiled in BRCA1
      functional and nonfunctional cell lines, revealing compounds (2, 3, and 5) of low
      cytotoxicity and excellent PARP-1 affinities (~4-8 nM). In comparison to AZD2461,
      these agents were found to be less stimulating of P-gp, suggesting that these
      compounds may be excellent candidates for neurological applications where blood
      brain barrier penetrance is sought.

PMID- 30198005
TI  - Reactive Epoxy Nanofiltration Membranes with Disulfide Bonds for the Separation
      of Multicomponent Chemical Mixtures.
AB  - This article reports the fabrication of organic solvent nanofiltration membranes
      containing a labile disulfide bond, which is broken by reaction with a chemical
      stimulus. These membranes are a new generation of smart membranes that have
      tailored selectivities and flux that can be altered by reacting with a chemical
      stimulus. The selectivity and flux of chemicals through the membranes was
      controlled by varying the concentration of disulfide bonds in the membrane. When
      the disulfide bonds were cleaved, the pores in the membrane became larger and
      yielded different separation properties. The membrane selectivity was changed by
      up to 70% and flux was increased up to 5*. The rapid change in selectivity of the
      membrane allowed for the separation of three-component mixtures. A three
      component mixture of 33.3% m-dinitrobenzene, 33.3% triphenylmethane, and 33.3%
      1,3,5-tris(diphenylamino)benzene (TDAB) was separated into three different
      fractions that were significantly enriched in one of the three molecules. The
      first fraction contained m-dinitrobenzene at 82% purity and 84% yield, the second
      fraction contained triphenylmethane at 67% purity and 49% yield, and the third
      fraction contained TDAB at 71% purity and 88% yield.

PMID- 30198006
TI  - Magnetic Field-Sensitive Radical Pair Dynamics in Polymethylene Ether-Bridged
      Donor-Acceptor Systems.
AB  - Donor-acceptor systems forming exciplexes are versatile models for the study of
      magnetic field effects (MFEs) on charge recombination reactions. The MFEs
      originate from singlet-triplet interconversion within transient radical ion pairs
      (RIPs), which exist in a dynamic equilibrium with the exciplexes. Here, we
      describe the synthesis and MFEs of the chain-linked N,N-dimethylaniline (DMA)/9
      methylanthracene (MAnt) donor-acceptor system MAnt-(CH2) n -O-CH2-CH2-DMA for n =
      6, 8, 10, and 16. The MFEs are found to increase with increasing chain length.
      Effects as large as 37.5% have been observed for the long-chain compound with n =
      16. The solvent dependence of the MFEs at magnetic field intensity 75 mT is
      reported. For the range of solvent static dielectric constants epsilons = 6.0
      36.0, the MFEs go through a maximum for intermediate polarities, for which the
      direct formation of RIPs prevails and their dissociation and reencounter are
      balanced. Field-resolved measurements (MARY spectra) are reported for solutions
      in butyronitrile. The MARY spectra reveal that for n = 8, 10, 16, the average
      exchange interaction is negligible during the coherent lifetime of the radical
      pair. However, singlet-triplet dephasing broadens the lineshape; the shorter the
      linker, the more pronounced this effect is. For n = 6, a dip in the fluorescence
      intensity reveals a nonzero average exchange coupling of the order of +/-5 mT. We
      discuss the field-dependence in the framework of the semiclassical theory taking
      spin-selective recombination, singlet-triplet dephasing, and exchange coupling
      into account. Singlet recombination rates of the order of 0.1 ns-1 and various
      degrees of singlet-triplet dephasing govern the spin dynamics. In addition,
      because of a small free energy gap between the exciplex and the locally excited
      fluorophore quencher pair, a fully reversible interconversion between the RIP,
      exciplex, and locally excited fluorophore is revealed by spectrally resolved MFE
      measurements for the long-chain systems (n = 10, 16).

PMID- 30198007
TI  - Hypercoordinated Oligosilanes Based on Aminotrisphenols.
AB  - The hypercoordinated silicon chlorides ClSi[(o-OC6H4)3N] (3) and
      ClSi[(OC6H2Me2CH2)3N] (5) were used for the synthesis of catenated derivatives
      (Me3Si)3SiSi[(o-OC6H4)3N] (9), (Me3Si)3SiSiMe2SiMe2Si(SiMe3)2Si[(o-OC6H4)3N]
      (11), and (Me3Si)3SiSi[(OC6H2Me2CH2)3N] (13) in reactions with (Me3Si)3SiK.THF
      (7) or (Me3Si)3SiK.[18-crown-6] (8). It was found that the nature of the
      (Me3Si)3SiK solvate determines the product of interaction, resulting in the
      formation of (Me3Si)3Si(CH2)4OSi[(OC6H2Me2CH2)3N] (12) or 13. Compounds obtained
      were characterized using multinuclear NMR and UV-vis spectroscopy and mass
      spectrometry. The molecular structures of 3, 9, and 11-13 were investigated by
      single-crystal X-ray analysis, featuring hypercoordinated Si atoms in a trigonal
      bipyramidal coordination environment with O atoms in the equatorial plane. The
      structure of the side product [N(CH2C6H2Me2O)3Si]2O (6) was also studied,
      indicating highly tetrahedrally distorted trigonal-bipyramidal environment at the
      Si atoms, which was confirmed by crystal density functional theory calculations
      indicating the very weak Si <- N interaction. The Si...N interatomic distances
      span a broad range (2.23-2.78 A). The dependence of structural and NMR parameters
      for hypercoordinated catenated compounds from the type of the ligand was
      established.

PMID- 30198008
TI  - Spatially Localized Synthesis and Structural Characterization of Platinum
      Nanocrystals Obtained Using UV Light.
AB  - Platinum nanocrystals with a fine control of the crystal domain size in the range
      1.0-2.2 nm are produced by tuning the NaOH concentration during the UV-induced
      reduction of H2PtCl6 in surfactant-free alkaline ethylene glycol. The colloidal
      solutions obtained are characterized by transmission electron microscopy and pair
      distribution function analysis, allowing analysis of both atomic and nanoscale
      structures. The obtained nanoparticles exhibit a face-centered cubic crystal
      structure even for the smallest nanoparticles, and the cubic unit cell parameter
      is significantly reduced with decreasing crystallite size. It is further
      demonstrated how the "UV-approach" can be used to achieve spatial control of the
      nucleation and growth of the platinum nanocrystals, which is not possible by
      thermal reduction.

PMID- 30198009
TI  - Low Intensity Ultrasound for Promoting Soft Tissue Healing: A Systematic Review
      of the Literature and Medical Technology.
AB  - Therapeutic ultrasound has been studied and used for the past seven decades to
      treat musculoskeletal injuries. Recently, a significant body of animal and human
      research has focused on the biomechanical effects of daily-applied, low intensity
      therapeutic ultrasound (LITUS) on soft tissue recovery. We performed a systematic
      review of the last two decades of LITUS literature to examine the effects on
      tendon, skeletal muscle, ligament, and tendon-bone junction injuries. LITUS
      facilitated tendon healing, with increased tensile strength and improved collagen
      alignment. For skeletal muscle and ligament injuries, LITUS increased cell
      proliferation during myoregeneration and improved tissue biomechanics (ultimate
      load, stiffness, energy absorption). LITUS aided tendon-bone junction healing
      through improved tissue function. Scientific evidence supports the use of LITUS
      to treat soft tissue injuries, and improve outcomes for musculoskeletal injuries
      and post-operative recovery. Lastly, we discuss the use of LITUS devices
      facilitating daily applied therapy in the home setting.

PMID- 30198010
TI  - Measurement of Change in Dynamic Factors Using the START:AV.
AB  - Historical approaches to violence risk assessment emphasized prediction of future
      violence and focused on static or historical risk factors. Consideration of
      dynamic factors as part of a comprehensive violence risk assessment approach may
      allow practitioners to better tailor treatment and risk management strategies.
      Limited research exists on whether risk assessment instruments can detect change
      in dynamic factors over time. The Short-Term Assessment of Risk and Treatability:
      Adolescent Version (START:AV) is a relatively new risk assessment instrument that
      considers both Vulnerabilities and Strengths on factors that are purportedly
      dynamic in nature. This study examined changes in START:AV factors between
      initial and follow-up assessments conducted approximately three months later as
      part of a pilot implementation at three juvenile justice residential facilities
      in a Southern state. Overall, findings revealed significant item-level changes on
      several factors, as well as reliable changes in total scores for 28% (reliable
      change index; 95% confidence interval) of adolescents.

PMID- 30198012
TI  - Microinteraction Ecological Momentary Assessment Response Rates: Effect of
      Microinteractions or the Smartwatch?
AB  - Mobile-based ecological-momentary-assessment (EMA) is an in-situ measurement
      methodology where an electronic device prompts a person to answer questions of
      research interest. EMA has a key limitation: interruption burden.
      Microinteraction-EMA(MUEMA) may reduce burden without sacrificing high temporal
      density of measurement. In MUEMA, all EMA prompts can be answered with 'at a
      glance' microinteractions. In a prior 4-week pilot study comparing standard EMA
      delivered on a phone (phone-EMA) vs. MUEMA delivered on a smartwatch (watch
      MUEMA), watch-MUEMA demonstrated higher response rates and lower perceived burden
      than phone-EMA, even when the watch-MUEMA interruption rate was 8 times more than
      phone-EMA. A new 4-week dataset was gathered on smartwatch-based EMA (i.e., watch
      EMA with 6 back-to-back, multiple-choice questions on a watch) to compare whether
      the high response rates of watch-MUEMA previously observed were a result of using
      microinteractions, or due to the novelty and accessibility of the smartwatch. No
      statistically significant differences in compliance, completion, and first-prompt
      response rates were observed between phone-EMA and watch-EMA. However, watch
      MUEMA response rates were significantly higher than watch-EMA. This pilot
      suggests that (1) the high compliance and low burden previously observed in watch
      MUEMA is likely due to the microinteraction question technique, not simply the
      use of the watch versus the phone, and that (2) compliance with traditional EMA
      (with long surveys) may not improve simply by moving survey delivery from the
      phone to a smartwatch.

PMID- 30198011
TI  - Tract-Specific White Matter Correlates of Age-Related Reward Devaluation Deficits
      in Macaque Monkeys.
AB  - Aim: Cognitive aging is known to alter reward-guided behaviors that require
      interactions between the orbitofrontal cortex (OFC) and amygdala. In macaques,
      OFC, but not amygdala volumes decline with age and correlate with performance on
      a reward devaluation (RD) task. The present study used diffusion magnetic
      resonance imaging (dMRI) methods to investigate whether the condition of the
      white matter associated with amygdala-OFC connectivity changes with age and
      relates to reward devaluation. Methods: Diffusion-, T1- and T2-weighted MRIs were
      acquired from adult and aged bonnet macaques. Using probabilistic tractography,
      fractional anisotropy (FA) estimates from two separate white matter tracts
      associated with amygdala-OFC connectivity, the uncinate fasciculus (UF) and
      amygdalofugal (AF) pathways, were obtained. Performance measures on RD and
      reversal learning (RL) tasks were also acquired and related to FA indices from
      each anatomical tract. Results: Aged monkeys were impaired on both the RD and RL
      tasks and had lower FA indices in the AF pathway. Higher FA indices from the
      right hemisphere UF pathway correlated with better performance on an object-based
      RD task, whereas higher FA indices from the right hemisphere AF were associated
      with better performance on an object-free version of the task. FA measures from
      neither tract correlated with RL performance. Conclusions: These results suggest
      that the condition of the white matter connecting the amygdala and OFC may impact
      reward devaluation behaviors. Furthermore, the observation that FA indices from
      the UF and AF differentially relate to reward devaluation suggests that the
      amygdala-OFC interactions that occur via these separate tracts are partially
      independent.

PMID- 30198014
TI  - Does increased expression of glucocorticoid receptor support application of
      antagonists to this receptor for the treatment of castration resistant prostate
      cancer?

PMID- 30198013
TI  - Robotic assisted VATS lobectomy for loco-regionally advanced non-small cell lung
      cancer.
AB  - Despite lung cancer screening programs and efforts at early detection, patients
      with non-small cell lung cancer continue to present with loco-regionally advanced
      disease. In particular, patients with positive mediastinal lymph nodes (N1/2,
      stage II/IIIA) present a challenge to the thoracic surgeon. The thorough
      lymphadenectomy required by these patients can be difficult to perform with
      standard VATS approaches. In addition, hilar fibrosis may result from the
      neoadjuvant therapy these patients generally receive, which complicates
      dissection of the vascular and bronchial structures. The robotic approach offers
      benefits that can help to address these challenges. While not ideal for the
      surgeon just learning robotic surgery, in experienced hands this is an effective
      tool to deal with loco-regionally advanced lung cancer safely and with optimal
      oncologic efficacy.

PMID- 30198017
TI  - CELF1 regulates gap junction integrity contributing to dilated cardiomyopathy.

PMID- 30198016
TI  - miRNA-211 stops the clock.

PMID- 30198018
TI  - A review of dual health care system use by veterans with cardiometabolic disease.
AB  - Many Veterans Affairs (VA) patients with the complications of cardiometabolic
      syndrome (CMS) use both VA and community providers and facilities outside of VA.
      Although dual health care systems increase care options, dual use also increases
      coordination needs. The fragmentation and duplication of health care due to the
      use of multiple facilities and providers may hinder effective care coordination,
      result in less efficient and more costly care, and lead to poorer outcomes. This
      article, which is based upon bibliographic searches in PubMed, reviews the
      evidence on dual use of VA and community health care by Veterans for acute
      myocardial infarction (AMI), congestive heart failure (CHF), and diabetes
      mellitus, the most common CMS complications requiring acute care and post-acute
      care services. A total of 179 articles were identified. After screening the full
      texts or abstracts of the 179 articles, 11 studies met the criteria, including
      two qualitative studies and 9 quantitative using administrative and Medicare
      records for veterans with AMI, CHF, or diabetes. Among the analytic studies, 3
      had a cross-sectional design and 6 were cohort studies. The results of studies
      completed to date suggest that dual healthcare system use by older male veterans
      with cardiometabolic conditions is not associated with improved outcomes and may
      lead to unnecessary tests or procedures and increased healthcare costs.
      Additional research is warranted to examine the prevalence of dual health care
      system use by male and female veterans during recent time periods and to compare
      outcomes among patients who receive only VA care, only community care, or both VA
      and community care.

PMID- 30198015
TI  - Acute retinal arterial ischemia.
AB  - Acute retinal arterial ischemia, which includes transient monocular vision loss
      (TMVL), branch retinal artery occlusion (BRAO), central retinal artery occlusion
      (CRAO) and ophthalmic artery occlusion (OAO), is most commonly the consequence of
      an embolic phenomenon from the ipsilateral carotid artery, heart or aortic arch,
      leading to partial or complete occlusion of the central retinal artery (CRA) or
      its branches. Acute retinal arterial ischemia is the ocular equivalent of acute
      cerebral ischemia and is an ophthalmic and medical emergency. Patients with acute
      retinal arterial ischemia are at a high risk of having further vascular events,
      such as subsequent strokes and myocardial infarctions (MIs). Therefore, prompt
      diagnosis and urgent referral to appropriate specialists and centers is necessary
      for further work-up (such as brain magnetic resonance imaging with diffusion
      weighted imaging, vascular imaging, and cardiac monitoring and imaging) and
      potential treatment of an urgent etiology (e.g., carotid dissection or critical
      carotid artery stenosis). Since there are no proven, effective treatments to
      improve visual outcome following permanent retinal arterial ischemia (central or
      branch retinal artery occlusion), treatment must focus on secondary prevention
      measures to decrease the likelihood of subsequent ischemic events.

PMID- 30198019
TI  - Collaborative Problem Solving in an Open-Ended Scientific Discovery Game.
AB  - Countless human pursuits depend upon collaborative problem solving, especially in
      complex, open-ended domains. As part of the growing technological support for
      such collaboration, an opportunity exists to design systems that actively guide
      and facilitate collaborative problem solving toward the most productive outcomes.
      A better understanding of the dynamics of open-ended collaboration on complex
      problems is needed to realize this opportunity. Motivated by this need for better
      understanding, we investigate the collaborative problem solving ecosystem of the
      scientific-discovery game Foldit. Our investigation is guided by two primary
      questions: how do the social aspects of Foldit impact an individual's behavior?
      and what factors have significant impact on group success? We find that
      collaboration and competition are associated with increased participation and
      that collaboration increases individual performance. We also find that measures
      of group skill, individual skill, and participation correlate with better group
      performance.

PMID- 30198020
TI  - Ribosome recycling is coordinated by processive events in two asymmetric ATP
      sites of ABCE1.
AB  - Ribosome recycling orchestrated by ABCE1 is a fundamental process in protein
      translation and mRNA surveillance, connecting termination with initiation. Beyond
      the plenitude of well-studied translational GTPases, ABCE1 is the only essential
      factor energized by ATP, delivering the energy for ribosome splitting via two
      nucleotide-binding sites by a yet unknown mechanism. Here, we define how
      allosterically coupled ATP binding and hydrolysis events in ABCE1 empower
      ribosome recycling. ATP occlusion in the low-turnover control site II promotes
      formation of the pre-splitting complex and facilitates ATP engagement in the high
      turnover site I, which in turn drives the structural re-organization required for
      ribosome splitting. ATP hydrolysis and ensuing release of ABCE1 from the small
      subunit terminate the post-splitting complex. Thus, ABCE1 runs through an
      allosterically coupled cycle of closure and opening at both sites consistent with
      a processive clamp model. This study delineates the inner mechanics of ABCE1 and
      reveals why various ABCE1 mutants lead to defects in cell homeostasis, growth,
      and differentiation.

PMID- 30198021
TI  - Mitochondrial ubiquinone-mediated longevity is marked by reduced cytoplasmic mRNA
      translation.
AB  - Mutations in the clk-1 gene impair mitochondrial ubiquinone biosynthesis and
      extend lifespan in C. elegans. We demonstrate here that this life extension is
      linked to the repression of cytoplasmic mRNA translation, independent of the
      alleged nuclear form of CLK-1. Clk-1 mutations inhibit polyribosome formation
      similarly to daf-2 mutations that dampen insulin signaling. Comparisons of total
      versus polysomal RNAs in clk-1(qm30) mutants reveal a reduction in the
      translational efficiencies of mRNAs coding for elements of the translation
      machinery and an increase in those coding for the oxidative phosphorylation and
      autophagy pathways. Knocking down the transcription initiation factor TAF-4, a
      protein that becomes sequestered in the cytoplasm during early embryogenesis to
      induce transcriptional silencing, ameliorates the clk-1 inhibition of
      polyribosome formation. These results underscore a prominent role for the
      repression of cytoplasmic protein synthesis in eukaryotic lifespan extension and
      suggest that mutations impairing mitochondrial function are able to exploit this
      repression similarly to reductions of insulin signaling. Moreover, this report
      reveals an unexpected role for TAF-4 as a repressor of polyribosome formation
      when ubiquinone biosynthesis is compromised.

PMID- 30198023
TI  - The interferon response as a common final pathway for many preconditioning
      stimuli: unexpected crosstalk between hypoxic adaptation and antiviral defense.
AB  - Despite major advances in understanding how the brain goes awry in disease,
      identification of therapeutics for neuroprotection in stroke remains an unsolved
      challenge. A promising strategy to delineate endogenous mechanisms of
      neuroprotection is to understand adaptive homeostatic transcription induced by
      sublethal ischemia. Homeostatic adaptation is defined as the body's restorative
      responses to stress. Activating adaptive homeostatic pathways can lead to
      transcription of a panoply of genes involved in cell survival and repair, can
      suppress pro-death signaling, and can stimulate metabolic changes congruent with
      survival. All of these mechanisms have been shown to be operative in protection
      induced by sublethal stress. In this context, central mediators of cellular
      adaptation to hypoxic and viral stress have been implicated in preconditioning.
      Here we present data that suggest an unexpected convergence in the pathways
      triggering adaptation to hypoxia and viral infection leading to preconditioning
      neuroprotection in the CNS.

PMID- 30198022
TI  - The Benefits of Genetic Addiction Risk Score (GARSTM) Testing in Substance Use
      Disorder (SUD).
AB  - Following 25 years of extensive research by many scientists worldwide, a panel of
      ten reward gene risk variants, called the Genetic Addiction Risk Score (GARS),
      has been developed. In unpublished work, when GARS was compared to the Addiction
      Severity Index (ASI), which has been used in many clinical settings, GARS
      significantly predicted the severity of both alcohol and drug dependency. In
      support of early testing for addiction and other RDS subtypes, parents caught up
      in the current demographic of 127 people, both young and old, dying daily from
      opiate/opioid overdose, need help. In the past, families would have never guessed
      that their loved ones would die or could be in real danger due to opiate
      addiction. Author, Bill Moyers, in Parade Magazine, reported that as he traveled
      around the United States, he found many children with ADHD and other spectrum
      disorders like Autism, and noted that many of these children had related
      conditions like substance abuse. He called for better ways to identify these
      children and treat them with approaches other than addictive pharmaceuticals. To
      our knowledge, GARS is the only panel of genes with established polymorphisms
      reflecting the Brain Reward Cascade (BRC), which has been correlated with the ASI
      MV alcohol and drug risk severity score. While other studies are required to
      confirm and extend the GARS test to include other genes and polymorphisms that
      associate with an hypodopaminergic trait, these results provide clinicians with a
      non-invasive genetic test. Genomic testing, such as GARS, can improve clinical
      interactions and decision-making. Knowledge of precise polymorphic associations
      can help in the attenuation of guilt and denial, corroboration of family gene-o
      grams; assistance in risk-severity-based decisions about appropriate therapies,
      including pain medications and risk for addiction; choice of the appropriate
      level of care placement (i.e., inpatient, outpatient, intensive outpatient,
      residential); determination of the length of stay in treatment; determination of
      genetic severity-based relapse and recovery liability and vulnerability;
      determination of pharmacogenetic medical monitoring for better clinical outcomes
      (e.g., the A1 allele of the DRD2 gene reduces the binding to opioid delta
      receptors in the brain, thus, reducing Naltrexone's clinical effectiveness); and
      supporting medical necessity for insurance scrutiny.

PMID- 30198025
TI  - SparkGIS: Efficient Comparison and Evaluation of Algorithm Results in Tissue
      Image Analysis Studies.
AB  - Algorithm evaluation provides a means to characterize variability across image
      analysis algorithms, validate algorithms by comparison of multiple results, and
      facilitate algorithm sensitivity studies. The sizes of images and analysis
      results in pathology image analysis pose significant challenges in algorithm
      evaluation. We present SparkGIS, a distributed, in-memory spatial data processing
      framework to query, retrieve, and compare large volumes of analytical image
      result data for algorithm evaluation. Our approach combines the in-memory
      distributed processing capabilities of Apache Spark and the efficient spatial
      query processing of Hadoop-GIS. The experimental evaluation of SparkGIS for
      heatmap computations used to compare nucleus segmentation results from multiple
      images and analysis runs shows that SparkGIS is efficient and scalable, enabling
      algorithm evaluation and algorithm sensitivity studies on large datasets.

PMID- 30198024
TI  - Current and emerging radiotherapy strategies for pancreatic adenocarcinoma:
      stereotactic, intensity modulated and particle radiotherapy.
AB  - The role of radiotherapy for locally advanced pancreatic cancer (LAPC) is unclear
      based on studies that used conventional doses and fractionation schedules. Modern
      radiotherapy techniques have not been studied in depth, however. We reviewed the
      literature on emerging methods of delivering higher doses of conformal
      radiotherapy using stereotactic body radiation, intensity modulated radiation,
      and particle beam radiation, highlighting clinical outcomes and toxicities. The
      literature review suggests low rates of acute and late toxicities when higher
      doses of radiation are given with careful attention to normal tissue dose
      constraints, including for stereotactic body radiotherapy (SBRT), escalated doses
      with intensity modulated radiation therapy (IMRT), and particle-based therapy.
      Retrospective evidence suggests prolonged survival for patients who receive
      biological equivalent doses above 70 Gy. Prospective trials that evaluate modern
      radiotherapy techniques are warranted for LAPC.

PMID- 30198026
TI  - Distraction Implantation. A New Technique in Total Joint Arthroplasty and Direct
      Skeletal Attachment.
AB  - Background: Using the marrow canal of a tubular bone as a holding compartment for
      implant stems has been the paradigm in total joint arthroplasty for more than a
      century, and for direct skeletal attachment of limb prostheses for about forty
      years. Both interventions rely on the osteogenesis in the inner walls of the
      marrow canal in a direction radially inwards. It so remains despite the frequent
      aseptic loosening of the implant stems caused by the resorption of the marrow
      canal's inner walls which increases the canal's diameter and reduces its capacity
      to hold the implant. Materials and Methods: To improve the bone-device bond, we
      suggest an implantation methodology that activates positive osteogenic remodeling
      in the circular direction rather than radially inwards. The rationale is that
      circular osteogenesis is a component of natural healing of bone fractures and its
      activating may mitigate the consequences of resorption caused by stress
      shielding, bone developmental growth and other factors. Results: Circular
      osteogenesis occurs in response to the distraction of slots precut into the bone
      tube. We call this methodology distraction implantation (DI) because of its debt
      to Ilizarov type distraction osteogenesis (DO). The methodology is accompanied by
      a design of an implant stem, and has been investigated in a previous pilot animal
      study. Conclusion: Distraction implantation is based on a component of natural
      healing of bone fractures and therefore has merit to be investigated further.

PMID- 30198027
TI  - Removing Phase Variables from Biped Robot Parametric Gaits.
AB  - Hybrid zero dynamics-based control is a promising framework for controlling
      underactuated biped robots and powered prosthetic legs. In this control paradigm,
      stable walking gaits are implicitly encoded in polynomial output functions of the
      robot configuration variables, which are to be zeroed via feedback. The biped
      output functions are parameterized by a suitable mechanical phasing variable
      whose evolution determines the biped gait progression during each step.
      Determining a proper phase variable, however, might not always be a trivial task.
      In this paper, we present a method for generating output functions from given
      parametric walking gaits without any explicit knowledge of the phase variables.
      Our elimination method is based on computing the resultant of polynomials, an
      algebraic tool widely used in computer algebra.

PMID- 30198029
TI  - GENERIC PRONOMINAL ANAPHORA : THE CASE OF THE ENGLISH SINGULAR THEY.

PMID- 30198030
TI  - High-performance double ion-buffering reservoirs of asymmetric supercapacitors
      based on flower-like Co3O4-G>N-PEGm microspheres and 3D rGO-CNT>N-PEGm aerogels.
AB  - Novel 3D flower-like Co3O4-G>N-PEGm composites have been synthesized by employing
      a solvothermal method, in which the incorporating graphene nanosheets are
      modified with methoxypolyethylene glycol (mPEG) via nitrene chemistry to form 2D
      macromolecular brushes. In Co3O4-G>N-PEGm, the flower-like Co3O4 microspheres can
      anchor on the G>N-PEGm nanosheets, corresponding to the coordination bonds
      between the lone pair of electrons on the mPEG polymer chains of the G>N-PEGm
      macromolecular brushes and cobalt ions. Owing to the novel structure, a high
      specific capacitance value of 1625.6 F g-1 at a current density of 0.5 A g-1 can
      be achieved in KOH solution. Meanwhile, 3D rGO-CNT>N-PEGm aerogels (GCA), as the
      negative electrode of electrical double-layer capacitor materials, exhibit a high
      reversible specific capacitance of 313.8 F g-1 at a current density of 2 A g-1.
      Based on the high electrochemical performance of both electrode materials, the
      double ion-buffering reservoirs of asymmetric supercapacitors configured with the
      Co3O4-G>N-PEGm as the positive electrode and 3D GCA as the negative electrode can
      deliver a high energy density of 34.4 W h kg-1 at a power density of 400 kW kg-1.

PMID- 30198031
TI  - Plasmonic vesicles with tailored collective properties.
AB  - Plasmonic nanoparticle assemblies have been exhibiting unique collective
      properties absent in their individual counterparts. However, it is an important
      challenge to manipulate those properties due to the difficulty in controlling the
      arrangement and distance between plasmonic nanoparticles. Herein, we propose an
      alternative strategy for manipulating the distance between gold nanoparticles on
      the plasmonic vesicles to afford tunable collective properties by changing the
      temperature. To reach this goal, a thermally responsive vesicle is self-assembled
      from an azobenzene-terminated homopolymer, poly(2-(2-ethoxyethoxy)ethyl acrylate)
      (Azo-PEEA). Gold nanoparticles are then decorated on its membrane to afford
      plasmonic vesicles, which can be grouped and fused into larger plasmonic vesicles
      when heated. Consequently, the gold nanoparticles come closer, creating local hot
      spots in the gap between adjacent gold nanoparticles, leading to the red shift of
      local surface plasmon resonance (LSPR) peaks and better surface-enhanced Raman
      scattering (SERS). Besides, the structure and the collective optical properties
      of the plasmonic vesicles can be reserved under various conditions, e.g.,
      different pH values, high salt concentration and relatively high temperature once
      they are heated up to 35  degrees C.

PMID- 30198028
TI  - Taking Stock of Tobacco Control Program and Policy Science and Impact in the
      United States.
AB  - The 60% decline in the prevalence of cigarette smoking among U.S. adults over the
      past 50 years represents a significant public health achievement. This decline
      was steered in part by national, state, and local tobacco control programs and
      policies, such as public education campaigns; widespread smoke-free air laws;
      higher cigarette prices that have been driven by large increases in federal,
      state, and local cigarette excise taxes; and other tobacco control policy and
      systems-level changes that discourage smoking. Using the MPOWER framework
      informed by the Centers for Disease Control and Prevention (CDC) Office on
      Smoking and Health and the World Health Organization (WHO), this paper reviews
      these accomplishments and identifies gaps in tobacco control policy
      implementation and additional research needed to extend these historic successes.

PMID- 30198032
TI  - Pt alloy nanoparticles decorated on large-size nitrogen-doped graphene tubes for
      highly stable oxygen-reduction catalysts.
AB  - Pt alloy nanoparticles supported on Vulcan XC-72 (Pt/C) are the most effective
      catalysts for kinetically sluggish oxygen reduction reaction (ORR) in proton
      exchange membrane fuel cells. However, significant performance degradation has
      been observed with the Pt/C catalysts due to agglomeration and Ostwald ripening
      of Pt nanoparticles largely resulting from the corrosion of carbon supports.
      Here, we developed a Pt alloy catalyst through annealing Pt nanoparticles
      deposited on nitrogen/metal co-doped large-size graphene tubes (NGTs). The in
      situ formation of PtM (M: Co and Ni) alloy during the annealing process
      contributes to the improvement of the catalytic activity and stability. During
      the accelerated stress tests (AST), after 20 000 potential cycles (0.6-1.0 V vs.
      RHE), the retained electrochemical surface area (ECSA) of the PtM/NGT catalyst is
      more than 2 times larger than that of the Pt/C catalyst. As for the AST tests of
      carbon corrosion, after 30 000 potential cycles (1.0-1.5 V vs. RHE) at room
      temperature, the NGT morphologies are well maintained and no ECSA loss of this
      PtM catalyst is observed, indicating excellent corrosion-resistance. Even at
      harsher 60  degrees C, the PtM/NGT catalyst exhibits only insignificant loss (6
      mV) of E1/2 while the Pt/C catalyst shows significant degradation (47 mV loss in
      E1/2). The improved stability of PtM/NGT catalyst is attributed to the highly
      graphitized NGTs and possible synergistic effects between the NGT carbon support
      and the PtM alloy nanoparticles.

PMID- 30198033
TI  - Ultrafast fabrication of nickel sulfide film on Ni foam for efficient overall
      water splitting.
AB  - Development of low-cost, high performance and stable non-noble electrocatalysts
      with both hydrogen evolution reaction (HER) and oxygen evolution reaction (OER)
      activities for overall water splitting is essential for future energy supply.
      Herein, for the first time, a facile and ultrafast synthetic method has been
      reported to fabricate nickel sulfide (Ni3S2) films on Ni foam (Ni3S2/NF) as
      efficient bifunctional electrodes for overall water splitting through direct
      dropping of mercaptoethanol solution followed by annealing at 300  degrees C for
      only 50 s. Thanks to the integrated three-dimensional (3D) configuration, the
      obtained Ni3S2/Ni foam exhibits excellent activity and stability for HER and OER
      with low overpotentials of 131 and 312 mV, respectively, to attain a current
      density of 10 mA cm-2 in alkaline media. Ni(OH)x species formed on the Ni3S2
      surface serves as the actual catalytic site during OER reaction. Given the well
      defined bifunctionality, an overall water-splitting device using two identical
      Ni3S2/NF electrodes delivers a current density of 10 mA cm-2 at a low cell
      voltage of 1.68 V in an alkaline water electrolyzer. This approach is promising
      as a simple method for depositing a wide range of useful transition metal sulfide
      electrocatalysts on corresponding metal substrate bifunctional electrodes for
      overall water splitting, shedding some light on the development of functional
      materials in energy chemistry.

PMID- 30198034
TI  - A highly antibacterial polymeric hybrid micelle with efficiently targeted
      anticancer siRNA delivery and anti-infection in vitro/in vivo.
AB  - Most of the diseases such as tumors are usually accompanied by microbial
      infection, especially after surgical operation, which prevents successful cancer
      therapy. It is necessary to develop a safe and efficient siRNA delivery vector
      with high anti-bacterial capability. Here, three multifunctional polymeric hybrid
      micelles (PHM1, PHM2 and PHM3) with high antimicrobial activity were prepared by
      mixing polymers PEG-b-P3/4HB-b-PEI-b-FA (EHP-FA) and PEG-b-P3/4HB-b-EPL (EHE)
      copolymer at different mixing ratios and evaluated for targeted siRNA delivery
      and anti-infection applications. The PHM micelles, taking advantage of the
      binding ability of EHE and the protection ability of EHP-FA, could effectively
      combine, protect siRNA, release complexed siRNA and target cancer cells.
      Additionally, PHM micelles displayed good hemocompatibility, lower cytotoxicity
      and higher gene silencing efficiency than commercial PEI (25 kDa) in A549, HeLa,
      HepG2 and C2C12 cells. Through optimizing the ratio of EHP-FA and EHE, PHM/sip65
      showed a high p65 gene silencing efficiency above 90% in various cancer cells,
      which were significantly higher than EHP-FA/sip65 alone and EHE/sip65 complexes.
      Furthermore, PHM2 micelles showed excellent antimicrobial activity towards
      positive bacteria (S. aureus) in vitro and in vivo. Our study may provide a
      facile strategy to develop multifunctional polymer gene vectors for highly
      promising siRNA delivery and anti-infection.

PMID- 30198035
TI  - Hedgehog-inspired nanostructures for hydrogel-based all-solid-state hybrid
      supercapacitors with excellent flexibility and electrochemical performance.
AB  - High-security deformable energy-storage devices that are mechanically robust,
      with considerable energy and power densities are becoming desirable for smart
      wearable electronics. Here, a highly flexible hydrogel-based all-solid-state
      hybrid supercapacitor was rationally designed and assembled, with unique
      NiCo2O4@NixCoyMoO4 (x : y = 3 : 1) nanostructures as the electrode, which was bio
      inspired by the curling up and relaxation of hedgehogs. The hybrid supercapacitor
      shows no obvious decay in capacitance during bending to different states,
      indicating its outstanding flexibility and mechanical stability. The capacitance
      was still maintained at 92.0% of the initial value, even after continuous bending
      for 3000 cycles. The highly monodisperse NiCo2O4@NixCoyMoO4 nanostructures
      releasing stress during bending is responsible for the favorable stability and
      flexibility. Furthermore, the hybrid supercapacitor displayed outstanding
      electrochemical performance, with a high specific capacitance of 207 F g-1 at 1 A
      g-1, a high energy density of 64.7 W h kg-1 at 749.6 W kg-1, and favorable
      cycling stability (nearly 100% after 10 000 cycles). The flexible hybrid
      supercapacitor could be charged with a solar cell and served as the power source
      to light up LEDs. This simple and reliable hybrid supercapacitor, with
      extraordinary mechanical stability and electrochemical performance, is a
      promising power source for smart wearable electronics.

PMID- 30198036
TI  - Correction: A three-dimensional metal grid mesh as a practical alternative to
      ITO.
AB  - Correction for 'A three-dimensional metal grid mesh as a practical alternative to
      ITO' by Sungwoo Jang et al., Nanoscale, 2016, 8, 14257-14263.

PMID- 30198037
TI  - In situ electrodeposition of polypyrrole onto TaSe2 nanobelts quasi-arrays for
      high-capacitance supercapacitor.
AB  - Transition metal dichalcogenides have recently revealed interesting physical
      properties which lead to promising applications for functional devices. TaSe2, as
      a member of transition metal dichalcogenides, attracts a great deal of attention
      as a layered electric conductor with low dimension and metallic nature. Herein,
      we prepare a three-dimensional conductive quasi-array based on 2H-TaSe2
      nanobelts, which are synthesized directly on a tantalum foil by one step surface
      assisted chemical vapor transport method. The conductive quasi-arrays are used as
      substrate for in situ electrodeposition of polypyrrole to form cylinder-like
      composite nanostructures. It is shown that the TaSe2 nanobelts can improve
      conductivity and stability of polypyrrole by acting as conductive and robust
      skeleton. A symmetric supercapacitor constructed from the composites demonstrates
      high areal capacitance of 835 mF cm-2 at a scan rate of 2 mV s-1, wide potential
      window of 1.2 V, and excellent cycling stability with 98.7% capacitance retention
      after 10 000 cycles. Meanwhile, the assembly process of the supercapacitor is
      quite simple because it does not need any additional current collector, binder or
      conductive additive. The nanocomposites have been verified to be a very effective
      way to improve electrochemical performance of polypyrrole, and are promising to
      be applied as supercapacitors.

PMID- 30198038
TI  - Constant-rate dissolution of InAs nanowires in radiolytic water observed by in
      situ liquid cell TEM.
AB  - Understanding the dissolution process and mechanism of materials in a liquid at
      the nanoscale is very important for both science and technology in many fields.
      Although the dissolution process of nanoparticles has been studied by many
      groups, the dissolution of one-dimensional (1D) nanomaterials with a high aspect
      ratio has seldom been directly observed with a high spatial resolution. In this
      paper, the dissolution process of 1D nanowires (NWs), InAs NWs as an example, in
      radiolytic water is studied by in situ liquid cell transmission electron
      microscopy. Different from most size-dependent dissolutions of nanoparticles, the
      dissolution rate of InAs NWs is found to be constant with reducing size down to
      ~5 nm in diameter. The kinetics of InAs NW dissolution in radiolytic water is
      investigated by analyzing the source supply, surface reaction and product
      diffusion steps in the dissolution process. We find surface reaction limited
      dissolution fits well with our experimental results and the activation energy
      should be constant during the whole dissolution process even when the diameter of
      InAs NWs is as small as 5 nm. The present results are significant for a
      quantitative understanding of liquid phase reactions for 1D systems and for
      design and optimization of dissolution processes.

PMID- 30198039
TI  - Enabling random lasing in an ultrabroad spectral range with robust platforms
      based on amorphous media.
AB  - Random lasing with coherent feedback has been achieved in an ultrabroad spectral
      range of 533-870 nm when employing robust platforms based on amorphous media to
      provide optical feedback and modulating the gain curve. The pump threshold of the
      resultant random lasing is comparable to those reported with strongly scattering
      centers in crystalline forms and highly efficient microfiber systems. The
      findings suggest that amorphous media could serve as the base of robust platforms
      to investigate light-matter interactions in complex media and to create highly
      efficient light-emitting devices.

PMID- 30198040
TI  - Organic nanoparticles based on Lewis-pair formation: observation of
      prototropically controlled dual fluorescence.
AB  - We successfully synthesize fluorescent organic nanoparticles of a Lewis-pair
      consisting of an amino-type hydrogen-bonding molecule (Lewis base) and a borinate
      derivative (Lewis acid). 2-(2'-Aminophenyl)benzothiazole (o-ABT) is chosen as the
      fluorophore. This molecule has a transferable proton in the amino group, but it
      does not exhibit ESIPT (excited-state intramolecular proton transfer) reaction in
      solution and thus shows a single normal emission solely from the enamine form.
      Organic nanoparticles are prepared by the reprecipitation method in which the
      fluorophore (o-ABT) in conjunction with a Lewis acid (diphenylborinic anhydride;
      DPBA) dissolved in a good solvent is rapidly injected into water under
      sonication. Interestingly, the nanoparticles produced exhibit a characteristic
      dual fluorescence that can be ascribed to the enamine and imine tautomers of o
      ABT generated in the ground-state prototropy, which can be revealed by UV-vis
      absorption and excitation spectroscopy, IR spectroscopy and computational
      approaches. In the o-ABT/DPBA Lewis-pair nanoparticles, highly Stokes-shifted
      emission from the imine tautomer is enhanced in comparison with that from the
      molecularly dissolved state, suggesting that the present nanofabrication
      methodology based on Lewis acid-base chemistry (or N-B bonding interaction) plays
      a key role in tuning the fluorescence colour for the new type of organic
      nanoparticle.

PMID- 30198041
TI  - A catalase-loaded hierarchical zeolite as an implantable nanocapsule for
      ultrasound-guided oxygen self-sufficient photodynamic therapy against pancreatic
      cancer.
AB  - Photodynamic therapy (PDT) is an alternative strategy for treating pancreatic
      cancer (PC) in clinics. However, the therapeutic efficacy is generally suppressed
      by inadequate oxygen supply in the hypoxic tumor microenvironment. Herein,
      hierarchical zeolite nanocarriers with hydrophilic mesoporous nanostructures and
      excellent biodegradability are synthesized via a one-pot wet chemical method. By
      co-loading with catalase and methylene blue (MB), a new type of oxygen self
      sufficient PDT platform, a zeolite-catalase-MB nanocapsule (ZCM nanocapsule), is
      developed. After precision implantation of the ZCM nanocapsule into the tumor
      area under the real-time ultrasound (US) imaging guidance, the nanocapsule with
      90% relative activity of equivalent free catalase enzyme efficiently modulates
      the tumor hypoxia and enhances the intratumoral US contrast by sustained
      decomposition of endogenous H2O2 and in situ production of O2 gas bubbles.
      Meanwhile, the MB loading in hierarchical zeolite matrices prevents the rapid
      leaching of the photosensitizer in tumor tissue, achieving a good sustained
      photosensitizer release effect. Based on the synchronous mechanisms, upon near
      infrared laser irradiation, the local PC cells are completely killed, and no
      therapy-induced toxicity and recurrence are observed. This highly biocompatible
      and biodegradable hierarchical nanozeolite would further facilitate the
      development of catalase-based catalytic nanomedicine for enhancing chemotherapy,
      radiotherapy and combination therapy.

PMID- 30198042
TI  - Controlled synthesis of hollow C@TiO2@MoS2 hierarchical nanospheres for high
      performance lithium-ion batteries.
AB  - In this manuscript, we utilize a facile and efficient step-by-step strategy to
      synthesize three-layered C@TiO2@MoS2 hierarchical nanocomposites. These novel
      hybrids serve as anode materials in lithium-ion batteries (LIBs). The designed
      structure, in which MoS2 nanosheets are uniformly grown on TiO2 coated carbon
      hollow spheres, can enhance the electrical conductivity of electrodes, shorten
      the diffusion length of Li+ ions, alleviate the expansion of electrode materials
      and provide more active sites for lithium ion storage. As anode materials for
      lithium-ion batteries (LIBs), the C@TiO2@MoS2 hierarchical nanocomposites exhibit
      a high initial specific capacity (1687 mA h g-1) and good cycling performance
      (993.2 mA h g-1 after 100 cycles at a current density of 0.2 A g-1). Furthermore,
      the C@TiO2@MoS2 electrode exhibits high rate capacities of 963, 860, 806, 743,
      703, 664 and 633 mA h g-1 at different current densities of 200, 500, 1000, 2000,
      3000, 4000 and 5000 mA h g-1, respectively. The electrochemical performances
      stated above prove that the as-prepared C@TiO2@MoS2 nanocomposites can be
      promising anode materials for high-performance lithium-ion batteries.

PMID- 30198043
TI  - Reinvestigation of the iodine-mediated phosphoramidation reaction of amines and
      P(OR)3 and its synthetic applications.
AB  - A systematic study on the iodine-mediated phosphoramidation reaction of amines
      and trialkyl phosphites was conducted, which not only disclosed the factors
      affecting the reaction but also revealed that it could proceed smoothly in CH2Cl2
      at room temperature in open air. Using this method, various phosphoramidates with
      different aliphatic amines and aromatic amines were synthesized in good to
      excellent yields. Our present investigation shows that this underused method is
      actually a mild, practical and general way to synthesize phosphoramidates and
      will have wide applications.

PMID- 30198044
TI  - Correction: Ti2C3Tx nanosheets as photothermal agents for near-infrared
      responsive hydrogels.
AB  - Correction for 'Ti2C3Tx nanosheets as photothermal agents for near-infrared
      responsive hydrogels' by Changyu Yang et al., Nanoscale, 2018, 10, 15387-15392.

PMID- 30198045
TI  - Giant magnetic anisotropy of a two-dimensional metal-dicyanoanthracene framework.
AB  - Design of novel two-dimensional (2D) magnetic materials with large magnetic
      anisotropy energy (MAE) is highly desirable for nanoscale magnetic devices.
      Through systematic first-principles calculations, we found a huge MAE up to 180
      meV in a 2D Ir-dicyanoanthracene (Ir-DCA) framework with the easy axis
      perpendicular to the sheet. Analysis of the electronic structures reveals that
      the ultra large MAE originates from the coupling between the spin down dxy and
      dx2-y2 orbitals in the minority spin channel. Moreover, the perpendicular MAE can
      be further enhanced to 220 meV by applying an external tensile biaxial strain
      (~3%). Finally, our calculations indicate that the unique magnetic properties of
      Ir-DCA can be retained when supported on a hexagonal boron nitride (h-BN)
      substrate. These features make the Ir-DCA framework a promising candidate for
      potential applications in spintronic devices at high temperatures.

PMID- 30198046
TI  - Sydnone-coumarins as clickable turn-on fluorescent sensors for molecular imaging.
AB  - Copper-catalyzed and copper-free sydnone-alkyne cycloaddition reactions have
      emerged as complementary click tools for chemical biology but their use in
      bioorthogonal labeling is still in its infancy. Herein, combinations of alkynes
      and coumarin-sydnones were screened for their ability to generate pyrazole
      products displaying strong fluoroscence enhancement compared to reactants. One
      sydnone was identified as a particularly suitable new turn-on probe for protein
      labeling.

PMID- 30198047
TI  - Stoichiometric network analysis of entropy production in chemical reactions.
AB  - We use stoichiometric network analysis (SNA) to obtain a flux-based approach for
      the evaluation and description of the entropy production and exchange for
      chemical reactions in open systems. For non-equilibrium stationary states (NESS)
      the production and exchange are expressed as functions over the convex cone of
      the stationary reaction rates, revealing the reaction pathways and elementary
      flux modes (EFM) responsible for both entropy production and balance. The
      analysis of the entropy production of EFMs leads to a unique description of the
      contribution of the coupling between linear or cyclic reaction network paths, and
      the fluxes due to the matter exchange of the system with the system's
      surroundings. Network stoichiometry leads to an independent proof and
      confirmation of Prigogine's theorem of minimum entropy production for the linear
      regime of non-equilibrium thermodynamics. Moreover, the non-linear thermodynamic
      regime allows us to test the validity of the General Evolution Criterion (GEC)
      for NESS in isothermal chemical networks in mechanical equilibrium.

PMID- 30198048
TI  - Positron emission tomography/computed tomography as a clinical diagnostic tool
      for anterior mediastinal tumors.
AB  - PURPOSE: The purpose of this study was to assess the usefulness of positron
      emission tomography/computed tomography (PET/CT) in the differential diagnosis of
      anterior mediastinal tumors. METHODS: A total of 94 patients with anterior
      mediastinal masses or nodules (male, n = 41; female, n = 53; age, 17-84 years)
      were retrospectively evaluated. All patients were evaluated by PET/CT and the
      masses or nodules were histologically diagnosed in our institution. RESULTS:
      Anterior mediastinal masses and nodules were classified into two disease
      categories: Low (thymic hyperplasia, thymoma, mature teratoma, and MALT lymphoma)
      and High (thymic carcinoid, thymic cancer, diffuse large B-cell lymphoma, T-cell
      lymphoblastic lymphoma, Hodgkin's lymphoma, and malignant germ cell tumors)
      groups. The sensitivity and specificity of maximum standardized uptake value
      (SUVmax) 7.5 for the detection of High group were 77% and 100%, respectively. The
      SUVmax distributions of the WHO histological thymoma types and Masaoka stage
      thymomas extensively overlapped. Masaoka stage III thymomas had significantly
      higher SUVmax than Masaoka stage I thymomas. Regarding the TNM classification,
      the SUVmax of T3 and T1b thymomas was higher than T1a thymoma. CONCLUSION:
      Although the SUVmax of each disease overlapped, PET/CT findings provided useful
      information for the differential diagnosis of anterior mediastinal masses.

PMID- 30198050
TI  - Clostridium septicum Myonecrosis Secondary to an Occult Small Bowel
      Adenocarcinoma.

PMID- 30198049
TI  - HIV-exposed uninfected infants: elevated cord blood Interleukin 8 (IL-8) is
      significantly associated with maternal HIV infection and systemic IL-8 in a
      Kenyan cohort.
AB  - BACKGROUND: In low and middle income countries, human immunodeficiency virus
      (HIV) exposed, uninfected (HEU) infants demonstrate higher morbidity and
      mortality than their unexposed counterparts. To determine possible immune
      correlates of this effect, we investigated the impact of in utero HIV exposure on
      the uninfected neonatal immune milieu and maternal factors mediating these
      abnormalities in a cohort of vaginally delivered mother-infants. Samples of
      delivery and cord blood plasma were selected from 22 Kenyan HIV-infected women
      and their HIV exposed uninfected (HEU) infants drawn from the pre-ARV era, while
      19 Kenyan HIV-uninfected (HU) women and their infants were selected from a
      control cohort. RESULTS: Compared to HU cord plasma, HEU cord plasma contained
      significantly higher levels of pro-inflammatory cytokines interleukins (IL)-6 and
      -8 (both p < 0.001) and significantly lower levels of CXC motif chemokine 11
      (CXC11) (p < 0.001). Mediation analysis demonstrated that maternal HIV infection
      status was a significant determinant of infant IL-8 responses: HEU status was
      associated with a ninefold higher infant:mother (cord:delivery) plasma levels of
      IL-8 (p < 0.005), whereas maternal viral load was negatively associated with HEU
      IL-8 levels (p = 0.04) and not associated with HEU IL-6 levels. CONCLUSIONS:
      Exposure to maternal HIV infection drives an increase in prenatal IL-8 that is
      partially mediated by maternal cytokine levels. Differences between maternal and
      infant cytokine levels strongly suggest independent modulation in utero,
      consistent with prenatal immune activation. Elevated pro-inflammatory signals at
      birth may interfere with T cell responses at birth and subsequently influence
      immune maturation and the risk of morbidity and mortality in HEU infants.

PMID- 30198052
TI  - Expression of PTGS2, PGFS and PTGFR during downregulation and restart of
      spermatogenesis following GnRH agonist treatment in the dog.
AB  - Prostaglandins (PGs) and prostaglandin endoperoxide synthase (PTGS) are
      considered to be relevant for spermatogenesis and steroidogenesis. PTGS2,
      prostaglandin F synthase (PGFS) and PGF receptor (PTGFR) are investigated in the
      adult male dog using the model of the GnRH-agonist implant downregulated canine
      testis and its subsequent restart of spermatogenesis following abolition of
      treatment (3, 6, 9, 12 weeks after implant removal). On the mRNA level (ratio),
      PTGS2, PGFS and PTGFR expression did not differ between downregulation, different
      stages of recovery of spermatogenesis and untreated adult controls (CG). On the
      protein level, Sertoli and Leydig cells in all samples and some peritubular cells
      stained immunopositive for PTGS2. In the tubular compartment, the percentage of
      the PTGS2-immunopositive area (PIA) and the mean PTGS2-staining intensity (gray
      scale, GS) did not differ between groups but in the interstitial compartment, the
      PIA (p = 0.0494) and the GS (p < 0.0001) were significantly upregulated during
      early recrudescence (week 3/6). Comparing downregulation by two GnRH-agonist
      implants with juvenile controls (JG) and CG, the mRNA expression (ratio) did not
      differ. In the tubular compartment, the GS (p = 0.0321) was significantly higher
      at downregulation compared to CG and in the interstitial compartment, the PIA (p
      = 0.0073) and the GS (p = 0.0097) were significantly higher in JG compared to
      downregulation/CG. PTGS2, PGFS and PTGFR mRNA and PTGS2 protein are regularly
      expressed in the adult, juvenile and downregulated canine testis and
      downregulation and subsequent recrudescence affect PTGS2 protein expression
      mainly in Leydig cells. PTGS2 expression in the downregulated testis resembles
      the one in seasonal Syrian hamster but not juvenile canine testis.

PMID- 30198051
TI  - Which is more important for cardiometabolic health: sedentary time, higher
      intensity physical activity or cardiorespiratory fitness? The Maastricht Study.
AB  - AIMS/HYPOTHESES: Our aim was to examine the independent and combined (cross
      sectional) associations of sedentary time (ST), higher intensity physical
      activity (HPA) and cardiorespiratory fitness (CRF) with metabolic syndrome and
      diabetes status. METHODS: In 1933 adults (aged 40-75 years) ST and HPA (surrogate
      measure for moderate to vigorous physical activity) were measured with the
      activPAL3. CRF was assessed by submaximal cycle-ergometer testing. Metabolic
      syndrome was defined according to the Adult Treatment Panel (ATP) III guidelines.
      Diabetes status (normal, prediabetes [i.e. impaired glucose tolerance and/or
      impaired fasting glucose] or type 2 diabetes) was determined from OGTT.
      (Multinomial) logistic regression analyses were used to calculate likelihood for
      the metabolic syndrome, prediabetes and type 2 diabetes according to ST, HPA and
      CRF separately and combinations of ST-CRF and HPA-CRF. RESULTS: Higher ST, lower
      HPA and lower CRF were associated with greater odds for the metabolic syndrome
      and type 2 diabetes independently of each other. Compared with individuals with
      high CRF and high HPA (CRFhigh-HPAhigh), odds for the metabolic syndrome and type
      2 diabetes were higher in groups with a lower CRF regardless of HPA. Individuals
      with low CRF and low HPA (CRFlow-HPAlow) had a particularly high odds for the
      metabolic syndrome (OR 5.73 [95% CI 3.84, 8.56]) and type 2 diabetes (OR 6.42
      [95% CI 3.95, 10.45]). Similarly, compared with those with high CRF and low ST
      (CRFhigh-STlow), those with medium or low CRF had higher odds for the metabolic
      syndrome, prediabetes and type 2 diabetes, irrespective of ST. In those with high
      CRF, high ST was associated with significantly high odds for the metabolic
      syndrome (OR 2.93 [95% CI 1.72, 4.99]) and type 2 diabetes (OR 2.21 [95% CI 1.17,
      4.17]). The highest odds for the metabolic syndrome and type 2 diabetes were
      observed in individuals with low CRF and high ST (CRFlow-SThigh) (OR [95% CI]:
      the metabolic syndrome, 9.22 [5.74, 14.80]; type 2 diabetes, 8.38 [4.83, 14.55]).
      CONCLUSIONS/INTERPRETATION: These data suggest that ST, HPA and CRF should all be
      targeted in order to optimally reduce the risk for the metabolic syndrome and
      type 2 diabetes.

PMID- 30198053
TI  - Pre-hospital lung ultrasound for cardiac heart failure and COPD: is it
      worthwhile?
AB  - BACKGROUND: Pre-hospital ultrasound is a new challenge and lung ultrasound could
      be an interesting opportunity in the pre-hospital medical service. The aim of our
      study was to evaluate the efficacy of lung ultrasound in out-of-hospital non
      traumatic respiratory insufficiency. METHODS: We planned a case-controlled study
      in the ULSS 5 ovest vicentino area (Vicenza-Italy) enrolling subjects with severe
      dyspnea caused by cardiac heart failure or acute exacerbation of chronic
      obstructive pulmonary disease. We compared drugs administration, oxygen delivery,
      and laboratory tests between those patients with ultrasound integrated management
      and those without ultrasound. RESULTS: Pre-hospital lung ultrasound had a high
      specificity (94.4%) and sensitivity (100%) for the correct identification of
      alveolar interstitial syndrome using B lines, whereas the percentages obtained
      with pleural effusion were lower (83.3, 53.3%, respectively). The patients with
      ultrasound integrated management received a more appropriate pharmacological
      therapy (p 0.01), as well as non-invasive ventilation (CPAP) was used more
      frequently in those with an acute exacerbation of chronic obstructive pulmonary
      disease (p 0.011). Laboratory tests and blood gases analysis were not significant
      different between the two study groups. In a sub-analysis of the patients with an
      A profile, we observed a significant lower concentration of PCO2 in those with an
      ultrasound integrated management (PCO2: 42.62 vs 52.23 p 0.049). According with
      physicians' opinion, pre-hospital lung ultrasound gave important information or
      changed the therapy in the 42.3% of cases, whereas it just confirmed physical
      examination in the 67.7% of cases. CONCLUSIONS: Pre-hospital lung ultrasound is
      easy and feasible, and learning curve is rapid. Our study suggests that cardiac
      heart failure and acute exacerbation of chronic obstructive pulmonary disease can
      be considered two indications for pre-hospital ultrasound, and can improve the
      management of patient with acute respiratory insufficiency.

PMID- 30198054
TI  - Three-dimensional analysis of dental arch forms in Italian population.
AB  - BACKGROUND: The aim of this study was the comparison of male and female upper and
      lower dental arch form in untreated Italian patients by 3D analysis, to find
      differences in shape, in transversal and longitudinal diameters between sexes,
      and to give a representative set of population's dental arch to clinicians in
      order to provide suitable orthodontic treatment. METHODS: The sample consisted of
      3D scans of dental casts deriving from 104 Italian untreated patients (Male = 35,
      Female = 69) in permanent dentition. An evaluation of the arch form was performed
      by angular and linear values on every patient using a 3D software
      (SolidWorks(r)). A Student's two-tailed t test was used to determine if the
      differences in measurements between the male and female groups were significant
      and the level of significance was set at P < 0.05. RESULTS: Statistically
      significant differences in upper and lower transversal and longitudinal diameters
      were found. Male arch widths were significantly larger than those of females.
      Male intercanine, intermolar, and interpremolar diameters were significantly
      greater than females. Dental arch depth was significantly smaller in the female
      group. Anterior upper dental arch form was flatter, wider, and less sharp in the
      female group. CONCLUSIONS: Basing on the anatomical arches differences found
      between sexes concerning Italian patients, it is suggested to have regard to each
      patient pre-treatment arch form, width, and depth during orthodontic treatment
      according to gender.

PMID- 30198055
TI  - Clinical characteristics of patients with bipolar disorder and premorbid
      traumatic brain injury: a cross-sectional study.
AB  - BACKGROUND: About one in ten diagnosed with bipolar disorder (BD) has experienced
      a premorbid traumatic brain injury (TBI), while not fulfilling the criteria of
      bipolar and related disorder due to another medical condition (BD due to TBI). We
      investigated whether these patients have similar clinical characteristics as
      previously described in BD due to TBI (i.e. more aggression and irritability and
      an increased hypomania/mania:depression ratio) and other distinct clinical
      characteristics. METHODS: Five hundred five patients diagnosed with BD type I,
      type II, or not otherwise specified, or cyclothymia were interviewed about
      family, medical, and psychiatric history, and assessed with the Young Mania
      Rating Scale (YMRS) and the Inventory of Depressive Symptoms Clinician Rated 30
      (IDS-C30). Principal component analyses of YMRS and IDS-C30 were conducted.
      Bivariate analyses and logistic regression analyses were used to compare clinical
      characteristics between patients with (n = 37) and without (n = 468) premorbid
      TBI. RESULTS: Premorbid TBI was associated with a higher YMRS disruptive
      component score (OR 1.7, 95% CI 1.1-2.4, p = 0.0077) and more comorbid migraine
      (OR 4.6, 95% CI 1.9-11, p = 0.00090) independently of several possible
      confounders. Items on disruptive/aggressive behaviour and irritability had the
      highest loadings on the YMRS disruptive component. Premorbid TBI was not
      associated with an increased hypomania/mania:depression ratio. CONCLUSIONS:
      Disruptive symptoms and comorbid migraine characterize BD with premorbid TBI.
      Further studies should examine whether the partial phenomenological overlap with
      BD due to TBI could be explained by a continuum of pathophysiological effects of
      TBI across the diagnostic dichotomy. Trial registration ClinicalTrials.gov:
      NCT00201526. Registered September 2005 (retrospectively registered).

PMID- 30198056
TI  - Constructing future scenarios as a tool to foster responsible research and
      innovation among future synthetic biologists.
AB  - The emerging field of synthetic biology, the (re-)designing and construction of
      biological parts, devices and systems for useful purposes, may simultaneously
      resolve some issues and raise others. In order to develop applications robustly
      and in the public interest, it is important to organize reflexive strategies of
      assessment and engagement in early stages of development. Against this backdrop,
      initiatives related to the concept of Responsible Research and Innovation (RRI)
      have also appeared. This paper describes such an initiative: the construction of
      future scenarios to explore the plausibility and desirability of potential
      synthetic biology innovations. We guided teams of synthetic biology students who
      participated in the large international Genetically Engineered Machines (iGEM)
      competition, in constructing scenarios aimed at exploring the plausibility and
      desirability of potential synthetic biology innovations. In this paper we aim to
      examine to what extent, and how, constructing such future scenarios contributes
      to RRI. In order to do so, we conducted observations and interviews to understand
      what kind of learning and reflection was promoted by constructing the scenarios
      in terms of four dimensions, which are discussed prominently in the literature on
      RRI: anticipation, inclusion, reflexivity and responsiveness. While we focus on
      how constructing future scenarios can contribute to strengthening RRI at a
      project (and individual) level, we also consider how far our experiment may
      foster RRI in the iGEM competition in general, and perhaps even inspire
      constructive collaboration between 'social scientists' and 'natural scientists'
      in the context of larger scientific research programmes.

PMID- 30198057
TI  - Phase I/II study of first-line combination therapy with sorafenib plus
      resminostat, an oral HDAC inhibitor, versus sorafenib monotherapy for advanced
      hepatocellular carcinoma in east Asian patients.
AB  - PURPOSE: Resminostat is an oral inhibitor of class I, IIB, and IV histone
      deacetylases. This phase I/II study compared the safety and efficacy of
      resminostat plus sorafenib versus sorafenib monotherapy as first-line therapy for
      advanced hepatocellular carcinoma (HCC). EXPERIMENTAL DESIGN: In phase I,
      resminostat (400 mg or 600 mg/day on days 1 to 5 every 14 days) was administered
      with sorafenib (800 mg/day for 14 days) to determine the recommended dose for
      phase II. In phase II, patients were randomized (1:1) to sorafenib monotherapy or
      resminostat plus sorafenib. The primary endpoint was time-to-progression (TTP).
      RESULTS: Nine patients (3: 400 mg, 6: 600 mg) were enrolled in phase I, and the
      recommended dose of resminostat was determined to be 400 mg/day. Then 170
      patients were enrolled in phase II. Median TTP/overall survival (OS) were
      2.8/14.1 months with monotherapy versus 2.8/11.8 months with combination therapy
      (Hazard Ratio [HR]: 0.984, p = 0.925/HR: 1.046, p = 0.824). The overall incidence
      of adverse events was similar in both groups (98.8% versus 100.0%). However,
      thrombocytopenia >= Grade 3 was significantly more frequent in the combination
      therapy group (34.5% versus 2.4%, p < 0.001). Subgroup analysis revealed that
      median TTP/OS was 1.5/6.9 months for monotherapy versus 2.8/13.1 months for
      combination therapy (HR: 0.795, p = 0.392/HR: 0.567, p = 0.065) among patients
      with a normal-to-high baseline platelet count (>= 150 * 103/mm3). CONCLUSIONS: In
      patients with advanced HCC, first-line therapy with resminostat at the
      recommended dose plus sorafenib showed no significant efficacy advantage over
      sorafenib monotherapy.

PMID- 30198058
TI  - Novel N-1 substituted fluoroquinolones inhibit human topoisomerase I activity and
      exhibit anti-proliferative activity.
AB  - Fluoroquinolone-class agents selectively target the bacterial type IIA
      topoisomerases DNA gyrase and topoisomerase IV, with a few exceptions that target
      eukaryotic type IIA topoisomerases. Fluoroquinolones bind and stabilize type IIA
      topoisomerase-DNA covalent complexes that contain a double-strand break. This
      unique mode of action is referred to as 'topoisomerase poisoning'. We discovered
      that two novel fluoroquinolones having aryl functionality at the N-1 position,
      UITT-3-217 (217) and UITT-3-227 (227), could inhibit the catalytic activity of
      human topoisomerase II without stabilizing topoisomerase-DNA complexes, i.e.,
      without poisoning it. Surprisingly, these compounds are more effective in
      inhibiting the catalytic activities of human and bacterial topoisomerase I. The
      National Cancer Institute's 60 human tumor cell lines screen revealed significant
      anti-proliferative activities with 217 and 227 against the majority of 60 cancer
      cell lines. A proof of concept in vivo efficacy study using an HT-29 xenograft
      model of human colorectal cancer showed that 217 could inhibit the proliferation
      of human colorectal cancer cells to a degree comparable to fluorouracil in mice.
      Although 227 also exhibited anti-proliferative activity, it was not as effective
      as 217 in this xenograft model. These novel fluoroquinolones may serve as
      promising lead compounds for the development of new anticancer drugs.

PMID- 30198062
TI  - A case of lymphomatoid papulosis, pityriasis lichenoides acuta, and mycosis
      fungoides coexistence.

PMID- 30198061
TI  - Multi-Indication Pricing: Nice in Theory but Can it Work in Practice?
AB  - For medicines with different valued indications (uses), multi-indication pricing
      implies charging different prices for different uses. In this article, we assess
      how multi-indication pricing could help achieve overall strategic objectives of
      pricing controls, summarise its advantages and disadvantages (vs. uniform
      pricing) and estimate the hypothetical impact on prices of moving towards multi
      indication pricing for specific oncologic medicines in Spain. International
      experience shows that multi-indication pricing can be implemented in real
      practice, and indeed a few initiatives are currently in use, albeit mostly
      applied indirectly through confidential pricing agreements that offer a way to
      discriminate prices across countries without altering list prices. However, some
      more sophisticated systems are in place in Italy, and more recently in Spain,
      where the objective is to monitor usage per patient/indication, and ultimately
      pay for outcomes. Based on the existing experience, we also outline six
      conditions required for multi-indication pricing. Multi-indication pricing is a
      useful tool to determine the relative prices of a drug for multiple (different
      valued) indications, but by itself will not offer the 'solution' to what the
      absolute price should be. That will be driven, among other things, by cost
      effectiveness thresholds, if they exist. Overall, we argue multi-indication
      pricing is nice in theory and it could work in practice, although changes in the
      manner in which medicines are priced, procured and monitored in clinical practice
      need to be applied.

PMID- 30198059
TI  - Impact of pregnancy on inborn errors of metabolism.
AB  - Once based mainly in paediatrics, inborn errors of metabolism (IEM), or inherited
      metabolic disorders (IMD) represent a growing adult medicine specialty.
      Individually rare these conditions have currently, a collective estimated
      prevalence of >1:800. Diagnosis has improved through expanded newborn screening
      programs, identification of potentially affected family members and greater
      awareness of symptomatic presentations in adolescence and in adulthood. Better
      survival and reduced mortality from previously lethal and debilitating conditions
      means greater numbers transition to adulthood. Pregnancy, once contraindicated
      for many, may represent a challenging but successful outcome. Successful
      pregnancies are now reported in a wide range of IEM. Significant challenges
      remain, given the biological stresses of pregnancy, parturition and the
      puerperium. Known diagnoses allow preventive and pre-emptive management.
      Unrecognized metabolic disorders especially, remain a preventable cause of
      maternal and neonatal mortality and morbidity. Increased awareness of these
      conditions amongst all clinicians is essential to expedite diagnosis and manage
      appropriately. This review aims to describe normal adaptations to pregnancy and
      discuss how various types of IEM may be affected. Relevant translational research
      and clinical experience will be reviewed with practical management aspects cited.
      Based on current literature, the impact of maternal IEM on mother and/or foetus,
      as well as how foetal IEM may affect the mother, will be considered. Insights
      gained from these rare disorders to more common conditions will be explored. Gaps
      in the literature, unanswered questions and steps to enhance further knowledge
      and systematically capture experience, such as establishment of an IEM-pregnancy
      registry, will be summarized.

PMID- 30198060
TI  - Optimizing the Use of Medications and Other Therapies in Infant Gastroesophageal
      Reflux.
AB  - Gastroesophageal reflux (GER) is the retrograde movement of gastric (and
      sometimes duodenal) contents into the esophagus. While the majority of GER is
      physiologic, for patients, it can be associated with symptoms. While some
      symptoms are merely bothersome (crying), others can be life threatening (cough,
      gagging, choking). The main driver of GER in infants is the frequent feedings
      that produce increased intra-abdominal pressure, which is known to trigger
      transient relaxations of the lower esophageal sphincter. The recent 2018 clinical
      practice guidelines reported by the North American and European Societies for
      Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN/ESPGHAN) have
      recommended non-pharmacologic management initially with subsequent consideration
      of brief trials with acid suppressants. The main target for these acid
      suppressants is the gastric parietal cells. Our review of the literature has
      revealed a paucity of data regarding the use of histamine-2 receptor antagonists
      and proton pump inhibitors in infants. Despite the absence of well-controlled
      clinical studies, the prescription rate of these medications has increased
      internationally. Risks to patients of all ages have become increasingly
      recognized, with new associations being reported all too often. Here we report
      our review of all pharmacologic modalities as well as some non-surgical options.

PMID- 30198063
TI  - Effects of dietary lysozyme levels on growth performance, intestinal morphology,
      immunity response and microbiota community of growing pigs.
AB  - BACKGROUND: Lysozyme has been studied as a potential alternative to antibiotics
      for animals in recent years. The aim of this study was to evaluate the effect of
      dietary lysozyme on growth performance, serum biochemical parameters, immune
      response and gut health of growing pigs. RESULTS: A total of 216 growing pigs
      (19.81 +/- 0.47 kg) were fed the diets supplemented with colistin sulfate at 20
      mg kg-1 (control), or lysozyme at 50 (L50) or 100 mg kg-1 (L100) diet for 30
      days. The results showed that pigs fed with L100 or control had greater average
      daily gain and gain-to-feed ratio than pigs in the L50 group. Pigs fed with L100
      or colistin had greater villus height to crypt depth ratio in jejunum compared
      with pigs in the L50 group. Pigs fed with L100 had greater serum immunoglobulin A
      and jejunal secretory immunoglobulin A than control and L50, but lower serum
      total protein and globulin than control. No differences were observed in the
      messenger RNA expression of genes related to mucosal cytokines, antioxidant
      capacity, enzyme activity, and barrier functions among three treatments. The
      caecal microflora evenness was lower in the L100 group than in the control or L50
      group by 16S ribosomal DNA sequencing. Phylogenetic investigation of communities
      by reconstruction of unobserved states analysis predicted that lysozyme may
      modify nutrient metabolism by changing intestinal microbial function of pigs.
      CONCLUSIONS: Pigs supplemented with 100 mg kg-1 lysozyme had similar growth
      performance and intestinal morphology as pigs fed with colistin. This was likely
      due to the improved systemic and gut immune responses and the reduced microbiota
      diversity by feeding 100 mg kg-1 lysozyme. (c) 2018 Society of Chemical Industry.

PMID- 30198064
TI  - Foal meat volatile compounds: effect of vacuum ageing on semimembranosus muscle.
AB  - BACKGROUND: Cooked meat flavor arises through a combination of thermally
      generated aroma volatile and nonvolatile compounds in a matrix of muscle fiber,
      connective tissue, and fat. Ageing could affect meat odor, taste, and flavor by
      the development of odor compounds in the raw product. The aim of the work is to
      assess the ageing effect on the volatile compounds profile by solid-phase
      microextraction and gas chromatography-mass spectrometry analysis of foal meat
      vacuum packaged for storage at 4  degrees C for a period of 14 days. RESULTS:
      Only pentane and 3,7-dimethylnonane were significantly affected by ageing time (P
      < 0.01). Octanal and nonanal presented an increasing trend with higher values at
      14 ageing days compared with six ageing days (P < 0.01). CONCLUSIONS: Ageing
      poorly affects the volatile compounds production of foal meat. Probably, 14 days
      is considered to be a short maturation time in vacuum packaging for foal meat.
      (c) 2018 Society of Chemical Industry.

PMID- 30198066
TI  - Spatiotemporal dynamics of Lutzomyia longipalpis and macro-habitat
      characterization using satellite images in a leishmaniasis-endemic city in
      Argentina.
AB  - The spatiotemporal population dynamics of Lutzomyia longipalpis (Lutz & Neiva,
      1912) (Diptera: Psychodidae) were evaluated in a city in Argentina in which
      visceral leishmaniasis is endemic. Over 14 sampling sessions, 5244 specimens of
      five species of Phlebotominae (Diptera: Psychodidae) were captured, of which 2458
      (46.87%) specimens were L. longipalpis. Generalized linear models were
      constructed to evaluate the associations between L. longipalpis abundance and
      explanatory variables derived from satellite images. The spatial variable
      'stratum' and the temporal variable 'season' were also included in the models.
      Three variables were found to have significant associations: the normalized
      difference vegetation index; land surface temperature, and low urban coverage.
      The last two of these were associated with L. longipalpis abundance only during
      summer and winter, respectively. This variation between seasons supports the
      development of models that include temporal variables because models of
      distributions of the abundance of a species may show different critical variables
      according to the climatic period of the year. Abundance decreased gradually
      towards the downtown area, which suggests that L. longipalpis responds to a meta
      population structure, in which rural-periurban source populations that persist
      over time may colonize adjacent areas. This information allows for a
      spatiotemporal stratification of risk, which provides public health authorities
      with a valuable tool to help optimize prevention measures against visceral
      leishmaniasis.

PMID- 30198067
TI  - Occupational exposures and parkinsonism among Shanghai women textile workers.
AB  - BACKGROUND: Endotoxin, a contaminant of cotton dust, is an experimental model for
      parkinsonism (PS). METHODS: We investigated associations between exposures to
      endotoxin, solvents, magnetic fields, and night shift work, and neurologist
      determined PS among Shanghai women textile workers, including 537 retired cotton
      factory workers ages >=50 years and an age-matched reference group of 286 retired
      textile workers not exposed to cotton dust. Repeat exams were conducted 2.5 years
      after enrollment among 467 cotton workers and 229 reference workers. RESULTS: We
      identified 39 prevalent PS cases and 784 non-cases. No consistent or
      statistically significant associations were observed for endotoxin, solvents,
      magnetic fields, or shift work with PS risk, severity, or progression.
      CONCLUSIONS: Despite the null findings, additional studies of endotoxin exposure
      and risk of PS in other well-characterized occupational cohorts are warranted in
      view of toxicological evidence that endotoxin is a pathogenic agent and its
      widespread occurrence in multiple industries worldwide.

PMID- 30198065
TI  - Comparison of inhibitory neuromuscular transmission in the Cynomolgus monkey IAS
      and rectum: special emphasis on differences in purinergic transmission.
AB  - KEY POINTS: Inhibitory neuromuscular transmission (NMT) was compared in the
      internal anal sphincter (IAS) and rectum of the Cynomolgus monkey, an animal with
      high gene sequence identity to humans. Nitrergic NMT was present in both muscles
      while purinergic NMT was limited to the rectum and VIPergic NMT to the IAS. The
      profile for monkey IAS more closely resembles humans than rodents. In both
      muscles, SK3 channels were localized to PDGFRalpha+ cells that were closely
      associated with nNOS+ /VIP+ nerves. Gene expression levels of P2RY subtypes were
      the same in IAS and rectum while KCNN expression levels were very similar. SK3
      channel activation and inhibition caused faster/greater changes in contractile
      activity in rectum than IAS. P2Y1 receptor activation inhibited contraction in
      rectum while increasing contraction in IAS. The absence of purinergic NMT in the
      IAS may be due to poor coupling between P2Y1 receptors and SK3 channels on
      PDGFRalpha+ cells. ABSTRACT: Inhibitory neuromuscular transmission (NMT) was
      compared in the internal anal sphincter (IAS) and rectum of the Cynomolgus
      monkey, an animal with a high gene sequence identity to humans. Electrical field
      stimulation produced nitric oxide synthase (NOS)-dependent contractile inhibition
      in both muscles whereas P2Y1-dependent purinergic NMT was restricted to rectum.
      An additional NOS-independent, alpha-chymotrypsin-sensitive component was
      identified in the IAS consistent with vasoactive intestinal peptide-ergic
      (VIPergic) NMT. Microelectrode recordings revealed slow NOS-dependent inhibitory
      junction potentials (IJPs) in both muscles and fast P2Y1-dependent IJPs in
      rectum. The basis for the difference in purinergic NMT was investigated.
      PDGFRalpha+ /SK3+ cells were closely aligned with nNOS+ /VIP+ neurons in both
      muscles. Gene expression of P2RY was the same in IAS and rectum (P2RY1>>P2RY2-14)
      while KCNN3 expression was 32% greater in rectum. The SK channel inhibitor apamin
      doubled contractile activity in rectum while having minimal effect in the IAS.
      Contractile inhibition elicited with the SK channel agonist CyPPA was five times
      faster in rectum than in the IAS. The P2Y1 receptor agonist MRS2365 inhibited
      contraction in rectum but increased contraction in the IAS. In conclusion, both
      the IAS and the rectum have nitrergic NMT whereas purinergic NMT is limited to
      rectum and VIPergic NMT to the IAS. The profile in monkey IAS more closely
      resembles that of humans than rodents. The lack of purinergic NMT in the IAS
      cannot be attributed to the absence of PDGFRalpha+ cells, P2Y1 receptors or SK3
      channels. Rather, it appears to be due to poor coupling between P2Y1 receptors
      and SK3 channels on PDGFRalpha+ cells.

PMID- 30198068
TI  - The Abc of Phosphonate Breakdown: A Mechanism for Bacterial Survival.
AB  - Bacteria have evolved advanced strategies for surviving during nutritional
      stress, including expression of specialized enzyme systems that allow them to
      grow on unusual nutrient sources. Inorganic phosphate (Pi ) is limiting in most
      ecosystems, hence organisms have developed a sophisticated, enzymatic machinery
      known as carbon-phosphorus (C-P) lyase, allowing them to extract phosphate from a
      wide range of phosphonate compounds. These are characterized by a stable covalent
      bond between carbon and phosphorus making them very hard to break down. Despite
      the challenges involved in both synthesizing and catabolizing phosphonates, they
      are widespread in nature. The enzymes required for the bacterial C-P lyase
      pathway have been identified and for the most part structurally characterized.
      Nevertheless, the mechanistic principles governing breakdown of phosphonate
      compounds remain enigmatic. In this review, an overview of the C-P lyase pathway
      is provided and structural aspects of the involved enzyme complexes are discussed
      with a special emphasis on the role of ATP-binding cassette (ABC) proteins.

PMID- 30198069
TI  - Dual aortic and portal perfusion at procurement prevents ischaemic-type biliary
      lesions in liver transplantation when using octogenarian donors: a retrospective
      cohort study.
AB  - Several risk factors for ischaemic-type biliary lesions (ITBL) after liver
      transplantation (LT) have been identified, but the role of portal vein perfusion
      at graft procurement is still unclear. This was a prospective study on double
      aortic and portal perfusion (DP) of liver grafts stratified by donor's decade
      (<60 yo; 60-69 yo; 70-79 yo and >=80 yo) versus similar historical cohorts of
      primary, adult grafts procured with single aortic perfusion (SP) only. The
      primary study aim was to assess the role of DP on the incidence of ITBL. There
      was no difference in the incidence of overall biliary complications according to
      procurement technique for recipients of grafts <80 years. A higher incidence of
      ITBL was observed for patients receiving grafts >=80 years and perfused through
      the aorta only (1.9 vs. 13.4%; P = 0.008). When analysing octogenarian grafts,
      donor male gender (HR = 6.4; P = 0.001), haemodynamic instability (HR = 4.9; P =
      0.008), and type-2 diabetes mellitus (DM2) (HR = 3.0; P = 0.03) were all
      independent risk factors for ITBL, while double perfusion at procurement (HR =
      0.1; P = 0.04) and longer donor intensive care unit (ICU) stay (HR = 0.7; P =
      0.04) were protective factors. Dual aortic and portal perfusion has the potential
      to reduce post-transplant ITBL incidence for recipients of octogenarian donor
      grafts. Larger series are needed to confirm this preliminary experience.

PMID- 30198070
TI  - Rural and metropolitan South Australian mental health workers' views about nurse
      prescribing: A thematic analysis.
AB  - Almost one third of the South Australian population reside in regional locations,
      which are serviced by just 8% of the State's total psychiatrist workforce.
      Consequently, access to psychotropic medications in regional South Australia (SA)
      can be challenging. Granting prescribing rights to mental health nurses (MHNs)
      located in regional settings presents an opportunity to increase consumer access
      to psychotropic medications. The aim of the study was to understand the
      perspectives of mental health workers (MHWs) practising in regional and
      metropolitan settings towards MHN prescribing. The study adopted a qualitative
      approach. Seventeen MHWs participated in three focus groups, including two in
      regional SA and one in a metropolitan site within the State of SA. Participants
      reported difficulties in accessing medicines in regional areas. The regional
      focus groups indicated that MHN prescribing may help to release psychiatrists'
      time and provide quicker assessment and diagnosis. By contrast, the metropolitan
      focus group expressed reservations about MHN prescribing. Participants indicated
      that suitable governance structures supported by appropriate education programmes
      were a necessary prerequisite for MHN prescribing of psychotropic medications.
      MHN prescribing may help to mitigate the impact of psychiatrist shortages in
      regional South Australia and possibly in other areas of the world where
      recruitment is a challenge. The provision of adequate education and the
      establishment of a suitable governance and support framework are considered
      necessary steps to progress MHN prescribing.

PMID- 30198071
TI  - Engagement and social interaction in dementia care settings. A call for
      occupational and social justice.
AB  - As full citizens, people with dementia are entitled to engage in social and
      occupational activities in residential care settings. Limitation or deprivation
      of choice and experience of valued occupations has been described elsewhere as
      occupational injustice. This research frames the unmet needs of people with
      dementia for occupation and social interaction, as issues of human rights and
      citizenship. It identifies a gap in current measurement tools of engagement in
      residential settings and in response, presents the Assessment Tool for
      Occupational and Social Engagement (ATOSE) as an objective measure of engagement.
      It examines results from a study of five residential care settings in Ireland
      using the ATOSE which included 73 residents with dementia and/or enduring mental
      health diagnoses. Residents spent on average, 38% of their time engaged and 62%
      of their time not engaged while in their communal sitting rooms. The ATOSE
      observations supported the rights of residents as citizens to have low levels of
      engagement addressed. A critical gerontology lens is employed to discuss concepts
      of citizenship, occupational justice, and social justice in the context of this
      research project.

PMID- 30198072
TI  - Reframing "participation" and "inclusion" in public health policy and practice to
      address health inequalities: Evidence from a major resident-led neighbourhood
      improvement initiative.
AB  - There is a need for greater conceptual clarity in place-based initiatives that
      seek to give residents of disadvantaged neighbourhoods more control over action
      to address the social determinants of health inequalities at a local level. In
      this article, we address this issue as it relates to the concepts of
      participation and inclusion. We draw on qualitative data generated during the
      first phase of the Communities in Control Study, a longitudinal multisite
      independent evaluation of the impact of Big Local on the social determinants of
      health and health inequalities. Big Local is a resident-led area improvement
      initiative in England, funded by the UK Big Lottery Fund. Initiatives focused on
      community empowerment are increasingly prominent in public health policy and
      practice globally. Approaches emphasise the promotion of greater control over
      decisions and action among individuals, groups, and communities, particularly
      those living in disadvantaged circumstances. However, when it comes to
      participation and inclusion in taking action and making decisions, the field is
      characterised by conceptual confusion. This risks undermining the impact of these
      initiatives. While participation and inclusion are necessary conditions for
      empowerment and collective control, they are not necessarily sufficient.
      Sufficiency requires attention to the breadth of participation (i.e., to
      inclusion) and to the depth of participation (i.e., the extent to which it is
      experienced as empowering and ultimately enables the exercise of collective
      control over decisions and actions). In observing how different Big Local
      resident-led partnerships across England are tackling the day-to-day challenges
      of engaging with their communities, we reveal the potential for policy and
      practice of reframing, and therefore clarifying (to highlight the different roles
      they have) the concepts of participation and inclusion in terms of depth and
      breadth.

PMID- 30198073
TI  - Effects of three probiotic Bacillus on growth performance, digestive enzyme
      activities, antioxidative capacity, serum immunity, and biochemical parameters in
      broilers.
AB  - This study was conducted to evaluate the effects of three Bacillus strains on
      growth performance, digestive enzyme activities, antioxidative capacity, serum
      immunity, and biochemical parameters in broilers. A total of 360 one-day-old Ross
      308 chicks were randomly allocated into four groups with three replicates per
      group (n = 30). The control group was fed a basal diet, whereas the other groups
      fed basal diet supplemented with either Bacillus subtilis natto or Bacillus
      licheniformis or Bacillus cereus (108  cfu/kg) for 42 days, respectively. The
      results revealed that the probiotic-treated groups markedly improved final body
      weight, daily weight gain, and the activities of trypsin, amylase, lipase and
      total protease (p < 0.05). Moreover, chicks fed probiotics had higher serum
      glutathione peroxidase activity and O2 - level, as well as hepatic catalase and
      superoxide dismutase activities, whereas malondialdehyde levels in serum and
      liver were reduced (p < 0.05). The significant increased IgA (p < 0.05) was
      observed in the probiotics groups as compared to the control group. In addition,
      dietary administration of probiotic strain markedly reduced the levels of serum
      ammonia, uric acid, total cholesterol, and triglyceride. Taken together, these
      three probiotic Bacillus showed beneficial effects on chickens with minor strain
      specificity.

PMID- 30198074
TI  - Beyond Global Charge: Role of Amine Bulkiness and Protein Fingerprint on
      Nanoparticle-Cell Interaction.
AB  - Amino groups presented on the surface of nanoparticles are well-known to be a
      predominant factor in the formation of the protein corona and subsequent cellular
      uptake. However, the molecular mechanism underpinning this relationship is poorly
      defined. This study investigates how amine type and density affect the protein
      corona and cellular association of gold nanoparticles with cells in vitro. Four
      specific poly(vinyl alcohol-co-N-vinylamine) copolymers are synthesized
      containing primary, secondary, or tertiary amines. Particle cellular association
      (i.e., cellular uptake and surface adsorption), as well as protein corona
      composition, are then investigated. It is found that the protein corona (as a
      consequence of "amine bulkiness") and amine density are both important in
      dictating cellular association. By evaluating the nanoparticle surface chemistry
      and the protein fingerprint, proteins that are significant in mediating particle
      cell association are identified. In particular, primary amines, when exposed on
      the polymer side chain, are strongly correlated with the presence of alpha-2-HS
      glycoprotein, and promote nanoparticle cellular association.

PMID- 30198075
TI  - Following the Kinetics of Barium Titanate Nanocrystal Formation in Benzyl Alcohol
      Under Near-Ambient Conditions.
AB  - In complex chemical syntheses (e.g., coprecipitation reactions), nucleation,
      growth, and coarsening often occur concurrently, obscuring the individual
      processes. Improved knowledge of these processes will help to better understand
      and optimize the reaction protocol. Here, a form-free and model independent
      approach, based on a combination of time-resolved small/wide-angle X-ray
      scattering, is employed to elucidate the effect of reaction parameters (such as
      precursor concentration, reactant stoichiometry, and temperature) on the
      nucleation, crystallization, and growth phenomena during the formation of
      nanocrystalline barium titanate. The strength of this approach is that it relies
      solely on the total scattered intensity (i.e., scattering invariant) of the
      investigated system, and no prior knowledge is required. As such, it can be
      widely applied to other synthesis protocols and material's systems. Through the
      scattering invariant, it is found that the amorphous-to-crystalline
      transformation of barium titanate is predominantly determined by the total amount
      of water released from the gel-like barium hydroxide octahydrate precursor, and
      three rate-limiting regimes are established. As a result of this improved
      understanding of the effect of varying reaction conditions, elementary boundary
      conditions can be set up for a better control of the barium titanate nanocrystal
      synthesis.

PMID- 30198076
TI  - Author Guidelines.

PMID- 30198077
TI  - Social Robots for Depression in Older Adults: A Systematic Review.
AB  - PURPOSE: In recent years, there has been an increase in the number of studies
      using social robots to improve psychological well-being. This systematic review
      investigates the effect of social robot interventions for depression in older
      adults. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta
      Analysis (PRISMA) method was used to identify and select existing studies. Nine
      electronic databases were searched for relevant studies. Methodological quality
      was assessed using the Joanna Briggs Institute Meta-Analysis of Statistics
      Assessment and Review Instrument. Screening, data extraction, and synthesis were
      performed by three reviewers. Inclusion criteria covered original quantitative
      studies investigating social robots for depression in older adults. FINDINGS:
      Seven studies were identified-six randomized controlled trials and one comparison
      study-with all classified as good quality. Social robot interventions consisted
      of companion, communication, and health-monitoring robots. Three studies
      presented promising outcomes for reducing depressive symptoms in older adults
      following social robot interventions, and three studies showed decreased, but
      nonsignificant, trends in depression scores. CONCLUSIONS: The results highlight
      the potential of social robot interventions for reducing depression in older
      adults. However, the evidence is not strong enough to formulate recommendations
      on clinical effectiveness. CLINICAL RELEVANCE: Social robots are being used with
      increasing frequency to potentially provide personal support to older adults
      living in long-term care facilities. Social robots can be used to help alleviate
      depressive symptoms when used in group activities.

PMID- 30198078
TI  - Less might be more: are disposable gloves and gowns necessary for cataract
      surgery?

PMID- 30198080
TI  - Supplement for the British Society of Paediatric Dentistry Annual Scientific
      Meeting, 11-14 September 2018, Dundee, Scotland.

PMID- 30198081
TI  - Editorial.

PMID- 30198079
TI  - Pregnancy course and outcomes in mosaic trisomy 16 confined to the placenta: A
      case series.

PMID- 30198083
TI  - Association of solidarity between adult children and older parents with cognitive
      decline.
AB  - AIM: The purpose of the present study was to investigate the association between
      older adults' contact with their adult children and their cognitive decline.
      Furthermore, contact with children was considered in terms of visual contact and
      non-visual contact. METHODS: Data from the Korean Longitudinal Study of Aging
      from 2006 to 2014 was assessed using longitudinal data analysis, and 6634
      participants were included at baseline with no missing information. The chi2 
      test and generalized linear mixed model with a binary distribution were used to
      investigate the association between solidarity of adult children and parents, and
      cognitive decline. RESULTS: Non-visual contact with the first-born child was
      significantly associated with cognitive decline. With daily contact as the
      reference: for two to three times weekly, the OR was 1.224 (P = 0.033); for two
      to three times monthly, the OR was 1.357 (P = 0.003); for five to six times
      yearly, the OR was 1.3816 (P = 0.008); and for very rarely, the OR was 1.786 (P <
      0.0002), showing a significant effect for all groups. In the final sex-, age- and
      marriage status-specific analysis, non-visual contact with the first-born child
      was significantly associated with cognitive decline for women, people aged <=64
      years and people who were married. CONCLUSIONS: The present study validated
      previous research on the importance of social contact, and further assessed
      different modes of contact to show that non-visual contact is more beneficial
      than visual contact in terms of cognitive decline. Geriatr Gerontol Int 2018; 18:
      1501-1506.

PMID- 30198082
TI  - The spectrum of chronic kidney disease in China: a national study based on
      hospitalized patients from 2010 to 2015.
AB  - AIM: To investigate the spectrum of chronic kidney disease (CKD) in China.
      METHODS: We utilized a large national in-patient database covering 878 class 3
      hospitals and involving 64.7 million adult patients in China from 2010 to 2015.
      The class 3 hospital in China are ranked as the top tier of medical system in
      China with at least 500 beds and the accreditation from health authorities. The
      specific causes of CKD were extracted from International Classification of
      Diseases-10 codes of discharge diagnoses. RESULTS: A total of 4.5% of
      hospitalized patients (1.8 million) were identified as CKD, with an increased
      percentage from 2010 (3.7%) to 2015 (4.7%). Increasing trends of diabetic kidney
      disease and hypertensive nephropathy were observed from 2010 to 2015 (19.5% vs.
      24.3% and 11.5% vs. 15.9%, respectively), especially for urban residents from
      north China. The proportion of obstructive nephropathy also increased gradually
      (10.3% in 2010 vs. 15.6% in 2015) and constituted another important cause of CKD
      for patients, especially for those from south China and rural residents.
      CONCLUSION: The spectrum of CKD is changing in China, with variations over time
      and geographic regions, which has implication regarding developing the prevention
      strategy of CKD. This article is protected by copyright. All rights reserved.

PMID- 30198085
TI  - Life satisfaction in young adults with cancer and the role of sociodemographic,
      medical, and psychosocial factors: Results of a longitudinal study.
AB  - BACKGROUND: Being diagnosed with and treated for cancer often has a strong impact
      on the life satisfaction (LS) of adolescents and young adults (AYAs). The current
      study investigated LS in AYA patients with cancer and determined associated
      factors. METHODS: Young patients (those aged 18-39 years at the time of
      diagnosis) with all malignant cancer sites and with a diagnosis made within the
      last 4 years were assessed. LS was measured at 2 measuring time points using the
      Questions on Life Satisfaction (FLZ-M). Differences in the FLZ-M and the 10
      subdomains (friends/acquaintances, leisure activities/hobbies, health,
      income/financial security, work/profession, housing situation, family life,
      children/family planning, partnership, and sexuality) between the 2 time points
      were calculated. Multiple regression analyses were conducted to determine factors
      associated with LS. RESULTS: A total of 514 patients (386 of whom were women)
      with a mean age at diagnosis of 29.6 years participated at both measurements. LS
      increased significantly in 5 domains with a small effect (Hedges g, 0.17) noted
      over time. The subdomains with the lowest LS were financial and professional
      situation, family planning, and sexuality. Significant associations with LS were
      found at baseline for sociodemographic, medical, and psychosocial variables
      (explained variance [R2 ]baseline = 0.41). At follow-up, psychosocial factors
      (positive social support, not having detrimental interactions, and lower
      perceived adjustment to the disease) remained most important for higher LS
      controlled for LS at baseline. Neither sociodemographic (except partnership) nor
      medical factors played a role (R2 follow-up = 0.54). CONCLUSIONS: Of all the
      variables examined, social support was found to be the most decisive factor
      associated with LS at both time points. With regard to LS, social support and
      adjustment to illness should be given more consideration in the medical care of
      AYA patients with cancer.

PMID- 30198084
TI  - Prevalence of glaucoma in the Northern Finland Birth Cohort Eye Study.
AB  - PURPOSE: To report the prevalence of glaucoma in the Northern Finland Birth
      Cohort (NFBC) Eye Study. METHODS: Subjects of the population-based Northern
      Finland 1966 Birth Cohort (NFBC), aged 45-49 years at the time of the field
      examination, were randomized to eye screening (50%) and control (50%) groups. The
      eye examination protocol included best corrected visual acuity (BCVA),
      measurements of intraocular pressure and central corneal thickness, Humphrey 24-2
      perimetry, stereoscopic optic nerve head (ONH) and retinal nerve fibre layer
      (RNFL) photography and imaging with optical coherence tomography (OCT), scanning
      laser polarimetry (GDx) and scanning laser ophthalmoscopy (HRT). The diagnosis of
      glaucoma was made by two independent general ophthalmologists and three
      independent glaucoma experts based on the evaluation of the ONH and RNFL
      photographs and the visual fields. RESULTS: Totally, 10 321 subjects of the NFBC
      main study were alive in Finland in 2011, and they were randomized to the NFBC
      Eye Study group (n = 5155) and the control group (n = 5166). Of the randomized
      subjects, 3039 of 5155 (59%) responded and had sufficient data for the study.
      Glaucoma was suspected in 172 subjects (5.7%) at the first phase of the
      evaluation protocol. The interobserver agreement between two screening
      ophthalmologists was moderately good (kappa value 0.54 [95% confidence intervals
      (CI) 0.46-0.61]). Finally, definite glaucoma was found in 33 subjects (1.1% [95%
      CI 0.8-1.5]). CONCLUSION: The study provides up-to-date information on the
      prevalence of glaucoma in a middle-aged Caucasian population in Finland. The
      baseline data reported here allows the evaluation of the cost-effectiveness of
      screening later on.

PMID- 30198086
TI  - Dietary salmon milt extracts attenuate hepatosteatosis and liver dysfunction in
      diet-induced fatty liver model.
AB  - BACKGROUND: Dietary nucleotides have several reported beneficial effects. Here,
      we report on a proteomic analysis of the effect of dietary nucleotides-rich
      salmon milt extract (SME) on the liver in a diet-induced fatty liver model.
      RESULTS: Young male normal ddY mice were fed a normal chow diet, high
      carbohydrate diet (HCD), HCD containing 1% SME, or HCD containing 10% SME for 5
      days following by a 2-day fast. Increased serum alanine transferase and aspartate
      transferase activities were observed in the HCD group and were significantly
      attenuated in the SME groups (P < 0.05). Hepatic steatosis was observed in all
      the HCD groups. Hepatic expression of Tnfalpha was significantly suppressed in
      the 10% SME group (P < 0.05). Comprehensive proteomic analysis of the liver in
      the SME groups revealed an increase in the levels of major proteins involved in
      mitochondrial bioenergetics, including peroxisome proliferator-activated receptor
      gamma co-activator 1 alpha, mitochondrial thioredoxin, cardiolipin synthase,
      peroxisome proliferator-activated receptor alpha, and carnitine
      palmitoyltransferase I. CONCLUSION: Dietary SME improved liver function in the
      diet-induced fatty liver model. Activation of mitochondrial biogenetic function
      might be involved in this process. (c) 2018 Society of Chemical Industry.

PMID- 30198087
TI  - Rich Chemistry in Inorganic Halide Perovskite Nanostructures.
AB  - Halide perovskites have emerged as a class of promising semiconductor materials
      owing to their remarkable optoelectronic properties exhibiting in solar cells,
      light-emitting diodes, semiconductor lasers, etc. Inorganic halide perovskites
      are attracting increasing attention because of the higher stability toward
      moisture, light, and heat as compared with their organic-inorganic hybrid
      counterparts. In particular, inorganic halide perovskite nanomaterials provide
      controllable morphology, tunable optoelectronic properties, and improved quantum
      efficiency. Here, the development controlled synthesis of desired inorganic
      halide perovskite nanostructures by various chemical approaches is described.
      Utilizing these nanostructures as platforms, anion exchange chemistry for wide
      compositional and optical tunabilities is described, and the rich structural
      phase transition phenomenon and mechanism investigated systematically.
      Furthermore, these nanostructures and extracted knowledge are applied to design
      photonic, photovoltaic, and thermoelectric devices. Finally, future directions
      and challenges toward improvement of the optical, electrical, and optoelectronic
      properties, exploration of the anion and cation exchange kinetics, and
      alleviation of the stability and toxicity issues in inorganic lead based halide
      perovskites are discussed to provide an outlook on this promising field.

PMID- 30198088
TI  - A review of the role of nurse leadership in promoting and sustaining evidence
      based practice.
AB  - AIM: This integrative review aims to explore how nursing leadership influences
      evidence-based practice in contemporary health care settings. BACKGROUND:
      Although managers and environmental ward culture have long been identified as
      being among the main barriers to evidence-based practice, there is little overall
      conceptualization and understanding of the specific role of nurse leaders in
      directly influencing and supporting this. EVALUATION: The team carried out an
      integrative literature review (n = 28) utilizing PubMed, CINAHL and the Cochrane
      Library (2006-2016). KEY ISSUES: The key role of leadership, the methodology
      used, and understanding and addressing barriers to or facilitators of the
      implementation of evidence-based practice emerged as key issues. CONCLUSION:
      Nurse managers have a particular influential role on the implementation of
      evidence-based practice in terms of providing a supportive culture and
      environment. For this they need to have an underlying knowledge but also to be
      aware of and address barriers to implementation, and understand the key role of
      nurse managers in creating and supporting the optimum environment. IMPLICATIONS
      FOR NURSING MANAGEMENT: Nurse managers need to facilitate and enhance nurses' use
      of evidence-based practice. Both managers and nurses need to have the necessary
      academic preparation, support and resources required for practising using an
      evidence base.

PMID- 30198089
TI  - CRISPR/Cpf1 facilitated large fragment deletion in Saccharomyces cerevisiae.
AB  - In this study, we focused on the applicability of CRISPR/Cpf1 in genome
      simplification of Saccharomyces cerevisiae and established a CRISPR/Cpf1 assisted
      method for rapid markerless large fragment deletion to facilitate laboratory
      evolution of geome of S. cerevisiae by rational genetic engineering. This method
      uses a Cpf1 expression plasmid and a crRNA array expression plasmid. The DNA
      fragment between two DSBs generated by CRISPR/Cpf1 can be cut off from the
      chromosome, along with re-ligation of the genomic endpoints of the DSBs. Using
      this method, the large DNA fragment of ~38 kb between the two genes of TRM10 and
      REX4 was successfully and rapidly deleted, which was verified by PCR and Sanger
      DNA Sequencing. This method is simple and rapid, and can be easily implemented
      for large fragment deletion in S. cerevisiae.

PMID- 30198090
TI  - Mullerian carcinosarcoma with neuroendocrine differentiation arising in hydrocele
      of the canal of Nuck.

PMID- 30198091
TI  - Recent Advances of Cellulose-Based Materials and Their Promising Application in
      Sodium-Ion Batteries and Capacitors.
AB  - Cellulose as the most abundant natural biopolymer on earth has shown promising
      potential because of its excellent physical, mechanical, and biocompatible
      properties, which are very important for sustainable energy storage systems
      (ESSs). In this review, a comprehensive summary of the applications involving all
      kinds and forms of cellulose in the advanced Na-related ESSs, including sodium
      ion batteries (SIBs) and sodium ion capacitors (SICs), is presented. For
      cellulose, the impact of various structures and surface chemical properties on
      the electrochemical performance is focused on. In particular, the latest
      developments in cellulose-based binders and separators are highlighted. In
      addition, an in-depth understanding of the structure and performance of electrode
      materials and the storage mechanism of a hard carbon anode derived from cellulose
      for SIBs is provided. Further, the manufacturing of full-cellulose-based SICs
      assembled by all parts of devices including hard carbon anodes, active carbon
      cathodes, binders, and separator based on cellulose or cellulose derivatives is
      reviewed. Finally, the prospects of cellulose-based energy storage systems on
      several issues that need further exploration are presented.

PMID- 30198092
TI  - Laparoscopic exploration and treatment for a mesenteric cyst lymphangioma in
      adults.

PMID- 30198093
TI  - Article alert: 200 items from 2014, grouped and indexed.
AB  - This ninth Article Alert installment's print component presents 200
      methodological articles about research synthesis published in 2014, all grouped
      by type of contribution and assigned descriptive keywords. More than 5300
      articles, book chapters, and other types of work from 2004 to 2008 and 2014 have
      been added to the archive component since the eighth installment. The online
      Supporting Information provides this and all previous installments' print- and
      archive-component records, most with a DOI name or other online identifier. In
      building the parent bibliographic compilation, more effort has been devoted
      recently to shorter pieces such as editorial material.

PMID- 30198094
TI  - Cutaneous epidermotropic metastasis of an oesophageal squamous cell carcinoma:
      Wound healing and transepidermal elimination as possible mechanisms for
      epidermotropism.

PMID- 30198095
TI  - Sleep differences in the UK between 1974 and 2015: Insights from detailed time
      diaries.
AB  - It is often stated that sleep deprivation is on the rise, with work suggested as
      a main cause. However, the evidence for increasing sleep deprivation comes from
      surveys using habitual sleep questions. An alternative source of information
      regarding sleep behaviour is time-use studies. This paper investigates changes in
      sleep time in the UK using the two British time-use studies that allow measuring
      "time in bed not asleep" separately from "actual sleep time". Based upon the
      studies presented here, people in the UK sleep today 43 min more than they did in
      the 1970s because they go to bed earlier (~30 min) and they wake up later (~15
      min). The change in sleep duration is driven by night sleep and it is
      homogeneously distributed across the week. The former results apply to men and
      women alike, and to individuals of all ages and employment status, including
      employed individuals, the presumed major victims of the sleep deprivation
      epidemic and the 24/7 society. In fact, employed individuals have experienced a
      reduction in short sleeping of almost 4 percentage points, from 14.9% to 11.0%.
      There has also been a reduction of 15 percentage points in the amount of conflict
      between workers work time and their sleep time, as measured by the proportion of
      workers that do some work within their "ideal sleep window" (as defined by their
      own chronotype).

PMID- 30198096
TI  - Changes in sensory proteins in the bladder urothelium of patients with chronic
      kidney disease and end-stage renal disease.
AB  - OBJECTIVE: Patients with chronic kidney disease (CKD) or end-stage renal disease
      (ESRD) frequently have lower urinary tract symptoms, such as frequency, urgency,
      or bladder pain. This study evaluated sensory protein expression in the bladder
      urothelium of patients with CKD or ESRD. METHODS: Twenty-seven patients with ESRD
      or CKD and urodynamically proven detrusor underactivity (DU; n = 8) or bladder
      oversensitivity (n = 19) were enrolled in the study. These patients, and 10
      controls, underwent cystoscopic biopsies of the urothelium. Western blotting
      analysis was used to examine the expression of sensory proteins, namely
      purinergic P2X3 , muscarinic M2 and M3 , and beta3 -adrenergic (AR) receptors, as
      well as inducible (i) and epithelial (e) nitric oxide synthase (NOS), in tissue
      samples. Expression was compared between CKD or ESRD patients and controls.
      RESULTS: P2X3 receptor expression was lower, whereas beta3 -AR was expression
      higher in the bladder urothelium of the patient group (ESRD and CKD combined)
      compared with controls. In addition, compared with controls, CKD patients had
      significantly lower P2X3 receptor expression, whereas ESRD patients had
      significantly higher M3 receptor expression. There were no significant
      differences in M2 receptor, eNOS, and iNOS expression between ESRD or CKD
      patients and controls. Patients with DU had significantly higher M2 and M3
      receptor expression. There were no significant differences in the expression of
      any protein between ESRD and CKD patients, regardless of the presence of bladder
      pain or anuria. CONCLUSION: Significantly decreased P2X3 receptor and increased
      beta3 -AR expression are seen in the bladder urothelium of patients with ESRD or
      CKD. The expression of these sensory proteins is not associated with decreased
      bladder capacity or anuria status in patients with ESRD or CKD.

PMID- 30198097
TI  - Atypical spindle cell/pleomorphic lipomatous tumor: A clinicopathologic,
      immunohistochemical, and molecular study of 20 cases.
AB  - Lipomatous tumors accompanied by spindle cell component are not frequently
      encountered, and there are still problems regarding their differential diagnosis,
      nature, and nomenclature. To contribute to ongoing efforts, we present the
      clinical, histologic, and immunohistochemical characteristics of 20 cases of
      spindle cell lipomatous tumors with atypical features that may also be called
      atypical spindle cell/pleomorphic lipomatous tumors. Of the patients, 13 were men
      and 7 were women with an average age of 57.5 years. The most commonly affected
      site was the extremities. Twelve tumors arose in the subcutaneous tissue, while
      eight cases were located in the deep soft tissues. Tumor margins were often ill
      defined with invasion into the surrounding tissues. Microscopic examination
      revealed a wide spectrum of histologic features. All cases consisted of poorly
      marginated proliferation of mildly atypical spindle cells set in a fibrous or
      myxoid stroma with a variable amount of adipocytic component showing variation in
      adipocyte size and scattered nuclear atypia and frequent univacuolated or
      multivacuolated lipoblasts. Tumor cellularity and the relative proportion of the
      components were highly variable. One tumor showed morphologic features evocative
      of dedifferentiation and another one exhibited histological features resembling
      pleomorphic liposarcoma. None of the patients had recurrence or metastasis at
      follow-up.

PMID- 30198098
TI  - How to do a self-assembled endosponge in the management of low colorectal
      anastomotic sinus.

PMID- 30198099
TI  - Cervical stabilization with polyaxial pedicle screw and rod construct in horses:
      A proof of concept study.
AB  - OBJECTIVE: To evaluate safety and efficacy of a novel technique for cervical
      stabilization. STUDY DESIGN: In vivo experimental. ANIMALS: Four normal adult
      quarterhorse crossbreed horses (2-4 years of age, > 250 kg). METHODS: One mid
      cervical spinal unit (C3-C4) was distracted with a porous metal interbody fusion
      device (IFD) and stabilized with a polyaxial pedicle screw and rod construct.
      Neurologic examinations were performed preoperatively and postoperatively.
      Radiographs of the fusion site and adjoining vertebrae were obtained
      preoperatively and monthly. Horses were euthanized at 8 months and spinal units
      were evaluated for osseointegration and implant safety via micro-computed
      tomography (CT), histology, and histomorphometry. RESULTS: The procedure was
      performed safely in all horses, without severe postoperative complications.
      Evaluation of radiographs revealed no implant failure, implant migration, or
      spinal unit instability in any of the horses. The presence of new bone formation
      around the screw and rod constructs was confirmed via micro-CT. No evidence of
      inflammation or iatrogenic damage was noted from histology. New bone was present
      within the IFD in all horses, with variable osseointegration on the cranial and
      caudal surfaces of the implant in 3 horses. CONCLUSION: The novel technique
      reported in the present study was safely applied to stabilize the C3-C4 spinal
      unit in the horses tested here and led to variable osseointegration within 8
      months. CLINICAL SIGNIFICANCE: The results of this study justify evaluation of
      this technique in horses with a diagnosis of cervical vertebral compressive
      myelopathy.

PMID- 30198100
TI  - Lactobacillus acidophilus Alleviated Salmonella-Induced Goblet Cells Loss and
      Colitis by Notch Pathway.
AB  - SCOPE: The intestinal mucosal barrier, including the mucus layer, protects
      against invasion of enteropathogens, thereby inhibiting infection. In this study,
      the protective effect of Lactobacillus on the intestinal barrier against
      Salmonella infection is investigated. The underlying mechanism of its effect,
      specifically on the regulation of goblet cells through the Notch pathway, is also
      elucidated. METHODS AND RESULTS: Here, the protective effect of Lactobacillus on
      alleviating changes in the intestinal barrier caused by Salmonella infection is
      explored. It has been found that Salmonella typhimurium colonizes the colon and
      damages colonic mucosa. However, Lactobacillus acidophilus ATCC 4356 alleviates
      the colitis caused by Salmonella infection. Moreover, S. typhimurium infection
      causes colonic crypt hyperplasia with increased PCNA+ cells, while L. acidophilus
      administration resolves these pathological changes. In addition, it has been
      further demonstrated that Salmonella results in severe colitis associated with
      goblet cells, and Lactobacillus improves colitis similarly associated with goblet
      cells. Salmonella infection induces goblet cell loss and reduces MUC2 expression
      by increasing Dll1, Dll4, and HES1 expression, while L. acidophilus reverses
      epithelial damage by balancing the Notch pathway. CONCLUSION: The study
      demonstrates that colitis improvement is controlled by Lactobacillus ATCC 4356 by
      regulation of the Notch pathway; this finding will be useful for prevention
      against animal S. typhimurium infection.

PMID- 30198101
TI  - Self-Control, Plan Quality, and Digital Delivery of Action Planning for Condom
      and Contraceptive Pill Use of 14-24-Year-Olds: Findings from a Clinic-Based
      Online Pilot Randomised Controlled Trial.
AB  - BACKGROUND: Inconsistent use of the contraceptive pill and condoms contributes
      significantly to poor sexual health outcomes for young people. There is evidence
      that action planning interventions may improve pill and condom use, but this
      approach is not systematically used in sexual healthcare. This study is the first
      to assess acceptability and feasibility of evaluating a digital intervention to
      support action plan formation for three sexual health behaviours with clinic
      attendees. It also considered the role of trait self-control and whether the
      intervention supported production of quality plans. METHODS: Eighty-eight
      integrated sexual health clinic attendees aged 14-24 years (M = 20.27 years) were
      recruited to a pilot randomised controlled trial (RCT). Of these, 67 also
      completed three-month follow-up. Measures included self-reported contraceptive or
      condom "mishaps", theory of planned behaviour variables, and a measure of self
      control. RESULTS: Descriptive analyses supported study acceptability and
      feasibility. The intervention supported pill and condom users to produce quality
      plans, though potential improvements were identified. Bivariate correlations
      suggested that high levels of trait self-control may negatively influence plan
      quality. Data suggest that the intervention may reduce pill or condom "mishaps".
      CONCLUSIONS: A future full RCT is likely feasible and brief digital action
      planning interventions may usefully be incorporated within sexual healthcare.

PMID- 30198102
TI  - Superiority of dutasteride 0.5 mg and tamsulosin 0.2 mg for the treatment of
      moderate-to-severe benign prostatic hyperplasia in Asian men.
AB  - OBJECTIVES: To assess the effectiveness and safety of dutasteride 0.5 mg +
      tamsulosin 0.2 mg combination compared with tamsulosin 0.2 mg in Asian men with
      moderate-to-severe benign prostatic hyperplasia. METHODS: A 4-week, single-blind,
      placebo, run-in was followed by a 2-year double-blind randomized controlled trial
      in men age >=50 years with symptomatic benign prostatic hyperplasia,
      International Prostate Symptom Score >=12, prostate volume >=30 cc, prostate
      specific antigen >=1.5 and <=10 ng/mL, peak urinary flow >5 and <=15 mL/s, and
      voided volume of >=125 mL. Participants were randomized to oral daily dutasteride
      0.5 mg + tamsulosin 0.2 mg combination or tamsulosin 0.2 mg. The primary efficacy
      end-point was change in International Prostate Symptom Score at year 2. RESULTS:
      Data from 607 participants showed a significant reduction in International
      Prostate Symptom Score (P < 0.05) at month 24, along with greater improvements (P
      <= 0.006) in peak urinary flow at every assessment and significant prostate
      volume reduction at months 12 and 24 (P < 0.001) in the combination group.
      Combination therapy was associated with a significant reduction in the risk of
      acute urinary retention or benign prostatic hyperplasia-related surgery (P =
      0.012), primarily due to a significant reduction in the risk of acute urinary
      retention (P = 0.005). The safety and tolerability profile of combination therapy
      was consistent with the known profiles for the individual monotherapies.
      CONCLUSIONS: Dutasteride 0.5 mg + tamsulosin 0.2 mg combination therapy showed
      better clinical outcomes than tamsulosin 0.2 mg monotherapy, making it an
      effective and safe treatment option for Asian men with moderate-to-severe benign
      prostatic hyperplasia.

PMID- 30198104
TI  - Development and future deployment of a five-year allograft survival model for
      kidney transplantation.
AB  - AIM: Identifying kidney transplant patients at highest risk for graft loss prior
      to loss may allow for effective interventions to improve 5-year survival.
      METHODS: We performed a ten-year retrospective cohort study of adult kidney
      transplant recipients (n=1,747). We acquired data from electronic health records,
      United Network of Organ Sharing, social determinants of health, natural language
      processing data extraction, and real-time capture of dynamically evolving
      clinical data obtained within 1-year of transplant; from which we developed a 5
      year graft survival model. RESULTS: 1,439 met eligibility; 265 (18.4%) of which
      experienced graft loss by 5-years. Graft loss patients were characterized by:
      older age, being African-American, diabetic, unemployed, smokers, having marginal
      donor kidneys, and cardiovascular comorbidities. Predictive dynamic variables
      included: low mean blood pressure, higher pulse pressures, higher heart rate,
      anemia, lower eGFR peak, increased tacrolimus variability, rejection, and
      readmissions. This Big Data analysis generated a 5-year graft loss model with an
      82% predictive capacity, vs 66% using baseline United Network of Organ Sharing
      data alone. CONCLUSION: Our analysis yielded a 5-year graft loss model
      demonstrating superior predictive capacity compared to United Network of Organ
      Sharing data alone, allowing post-transplant individualized risk-assessed care
      prior to transitioning back to community care. This article is protected by
      copyright. All rights reserved.

PMID- 30198103
TI  - Neuroprotective effect of carnosine in the olfactory bulb after vanadium
      inhalation in a mouse model.
AB  - Carnosine (beta-alanyl-L-histidine) is synthesized in the olfactory system, has
      antioxidant activity as a scavenger of free radicals and has been reported to
      have neuroprotective action in diseases which have been attributed to oxidative
      damage. In neurodegenerative disorders, such as Parkinson's and Alzheimer's
      diseases, impairment of olfactory function has been described. Vanadium
      derivatives are environmental pollutants, and its toxicity has been associated
      with oxidative stress. Vanadium toxicity on the olfactory bulb was reported
      previously. This study investigates the neuroprotective effect of carnosine on
      the olfactory bulb in a mice model of vanadium inhalation. Male mice were divided
      into four groups: vanadium pentoxide (V2 O5 ) [0.02 mol/L] inhalation for one
      hour twice a week; V2 O5 inhalation plus 1 mg/kg of carnosine administered daily;
      carnosine only, and the control group that inhaled saline. The olfactory function
      was evaluated using the odorant test. Animals were sacrificed four weeks after
      exposure. The olfactory bulbs were dissected and processed using the rapid Golgi
      method; cytological and ultrastructural analysis was performed and
      malondialdehyde (MDA) concentrations were measured. The results showed evidence
      of olfactory dysfunction caused by vanadium exposure and also an increase in MDA
      levels, loss of dendritic spines and necrotic neuronal death in the granule
      cells. But, in contrast, vanadium-exposed mice treated with carnosine showed an
      increase in dendritic spines and a decrease in neuronal death and in MDA levels
      when compared with the group exposed to vanadium without carnosine. These results
      suggest that dendritic spine loss and ultrastructural alterations in the granule
      cells induced by vanadium are mediated by oxidative stress and that carnosine may
      modulate the neurotoxic vanadium action, improving the olfactory function.

PMID- 30198105
TI  - Polyanionic Polydentate Europium Complexes as Ultrabright One- or Two-photon
      Bioprobes.
AB  - A family of europium (III) complexes based on a polydentate ligand functionalized
      by charge-transfer antennae presents remarkable one- and two-photon photophysical
      proper-ties in water or buffer. A detailed analysis of their emission properties
      suggests that the wrapping of the ligand around the central rare-earth ion
      results in an overall Cs symmetry in agreement with the theoretical simulation
      and that about 65-70 % of the emission intensity is concentrated in the
      hypersensitive 5 D0 ->7 F2 transition at 615 nm. Their brightness is excellent,
      in the range of the best lanthanide bioprobes making them very attractive for bio
      imaging experiments.

PMID- 30198106
TI  - A strategy for OCT estimation of the optic nerve head pigment epithelium central
      limit-inner limit of the retina minimal distance, PIMD-2pi.
AB  - PURPOSE: To develop a semi-automatic algorithm for estimation of pigment
      epithelium central limit-inner limit of the retina minimal distance averaged over
      2pi radians (PIMD-2pi) and to estimate the precision of the algorithm. Further,
      the variances in estimates of PIMD-2pi were to be estimated in a pilot sample of
      glaucomatous eyes. METHODS: Three-dimensional cubes of the optic nerve head (ONH)
      were captured with a commercial SD-OCT device. Raw cube data were exported for
      semi-automatic segmentation. The inner limit of the retina was automatically
      detected. Custom software aided the delineation of the ONH pigment epithelium
      central limit resolved in 500 evenly distributed radii. Sources of variation in
      PIMD estimates were analysed with an analysis of variance. RESULTS: The estimated
      variance for segmentations and angles was 130 MUm2 and 1280 MUm2 , respectively.
      Considering averaging eight segmentations, a 95 % confidence interval for mean
      PIMD-2pi was estimated to 212 +/- 10 MUm (df = 7). The coefficient of variation
      for segmentation was estimated at 0.05. In the glaucomatous eyes, the within
      subject variance for captured volumes and for segmentations within volumes was 10
      MUm2 and 50 MUm2 , respectively. CONCLUSION: The developed semi-automatic
      algorithm enables estimation of PIMD-2pi in glaucomatous eyes with relevant
      precision using few segmentations of each captured volume.

PMID- 30198107
TI  - The safety and efficacy of daylight photodynamic therapy in the treatment of
      actinic keratoses: a systematic review and meta-analysis.
AB  - Daylight photodynamic therapy (DLPDT) is a novel therapeutic approach for actinic
      keratoses (AKs). This study aimed to evaluate the safety and efficacy of DLPDT in
      treating patients with AKs as compared to conventional photodynamic therapy
      (CPDT). PubMed, EMBASE, Web of Science, and the Cochrane Central Register of
      Controlled Trials were searched for relevant randomized controlled trials (RCTs)
      published before November 2017, based on the following search terms: "solar
      keratoses", "actinic keratoses", "photodynamic therapy", "daylight photodynamic
      therapy", "conventional photodynamic therapy", and "randomized". The complete
      response rate, patient satisfaction, and patient-reported pain after intervention
      with DLPDT or CPDT were primarily measured. Sensitivity analysis was conducted to
      determine the reliability of results. Begg's and Egger's tests were used to
      assess the likelihood of publication bias. Eight RCTs, comprising a total of 424
      patients with AKs treated with DLPDT or CPDT, were included. No significant
      difference was found between the lesion response rate and the mean lesion
      response in a comparison of DLPDT and CPDT treatments. Generally, DLPDT was
      associated with higher patient satisfaction than CPDT. The patients who underwent
      DLPDT experienced less pain than those who underwent CPDT. Most of our results
      were of high stability and low sensitivity. Meanwhile, no statistical evidence of
      publication bias among studies was found under all comparisons. In conclusion,
      DLPDT is a safe and effective therapy, which could help in selecting the most
      appropriate therapeutic method for treating AKs and in guiding physicians to
      optimize treatment strategies.

PMID- 30198108
TI  - Retracing the Hawaiian silversword radiation despite phylogenetic, biogeographic,
      and paleogeographic uncertainty.
AB  - The Hawaiian silversword alliance (Asteraceae) is an iconic adaptive radiation.
      However, like many island plant lineages, no fossils have been assigned to the
      clade. As a result, the clade's age and diversification rate are not known
      precisely, making it difficult to test biogeographic hypotheses about the
      radiation. In lieu of fossils, paleogeographically structured biogeographic
      processes may inform species divergence times; for example, an island must first
      exist for a clade to radiate upon it. We date the silversword clade and test
      biogeographic hypotheses about its radiation across the Hawaiian Archipelago by
      modeling interactions between species relationships, molecular evolution,
      biogeographic scenarios, divergence times, and island origination times using the
      Bayesian phylogenetic framework, RevBayes. The ancestor of living silverswords
      most likely colonized the modern Hawaiian Islands once from the mainland
      approximately 5.1 Ma, with the most recent common ancestor of extant silversword
      lineages first appearing approximately 3.5 Ma. Applying an event-based test of
      the progression rule of island biogeography, we found strong evidence that the
      dispersal process favors old-to-young directionality, but strong evidence for
      diversification continuing unabated into later phases of island ontogeny,
      particularly for Kaua'i. This work serves as a general example for how
      diversification studies benefit from incorporating biogeographic and
      paleogeographic components.

PMID- 30198109
TI  - Phenotyping photosynthesis on the limit - a critical examination of RACiR.

PMID- 30198110
TI  - Facial monomorphic papules.

PMID- 30198111
TI  - Ethnographic study of the use of interventions during the second stage of labor
      in Jeddah, Saudi Arabia.
AB  - BACKGROUND: Routine use of medical interventions during labor has been identified
      as a clinical area for concern, since such routinized practice is not consistent
      with an evidence-based approach to care and continues to increase despite efforts
      to encourage normal childbirth. Therefore, the aim of our study was to explore
      maternity health professionals' use of interventions during the second stage of
      labor in two hospitals in Jeddah, Saudi Arabia, to understand what influences
      their decision-making and practices. METHODS: This was an exploratory study using
      an ethnographic approach. Data collection methods included participant
      observations of 19 labors and births (n = 8 at City Hospital and n = 11 at King's
      Hospital) and semi-structured interviews with 29 health care professionals. In
      addition, the hospital labor and delivery ward policies and guidelines from those
      hospitals were collected. Data were analyzed thematically. RESULTS: Medical
      interventions were used during the second stage of labor routinely, regardless of
      clinical indication. Three core influences that shaped the clinical decision
      making were identified as follows: (a) organizational culture, (b) a medical
      concept of birth, and (c) a hierarchical system of control. We suggest that the
      clinical decision-making and routine practice in this setting arises out of the
      interface between these three core influences whereby hierarchical control and
      clinicians' exercise of power and feelings of powerlessness are fundamental
      drivers for an organizational culture of medicalized childbirth, despite the
      differing models of childbirth which professionals described. CONCLUSIONS:
      Clinical decisions relating to the use of interventions during childbirth are
      both complex and socially negotiated. The findings reflect the complexity of the
      use of interventions during the second stage of labor and the multiple influences
      on professionals' practices. We have shown how three key influences interact to
      shape clinical decision-making during the second stage of labor in this cultural
      setting and how the use of medical interventions can be analyzed as an
      illustration of the power dynamic in the maternity health care system. We suggest
      that written policies are insufficient to bring about evidence-based practice and
      approaches to change need to take into account these different levels of
      influence.

PMID- 30198112
TI  - Home births-Where are we heading?

PMID- 30198113
TI  - Regional investigation of lung function and microstructure parameters by
      localized 129 Xe chemical shift saturation recovery and dissolved-phase imaging:
      A reproducibility study.
AB  - PURPOSE: To evaluate the reproducibility and regional variation of parameters
      obtained from localized 129 Xe chemical shift saturation recovery (CSSR) MR
      spectroscopy in healthy volunteers and patients with chronic obstructive
      pulmonary disease (COPD) and to compare the results to 129 Xe dissolved-phase MR
      imaging. METHODS: Thirteen healthy volunteers and 10 COPD patients were scanned
      twice using 129 Xe dissolved-phase imaging, CSSR, and ventilation imaging
      sequences. A 16-channel phased-array coil in combination with the regularized
      spectral localization achieved by sensitivity heterogeneity (SPLASH) method was
      used to perform a regional analysis of CSSR data. Lung function and
      microstructural parameters were obtained using Patz model functions and their
      reproducibility was assessed. RESULTS: The Patz model alveolar wall thickness
      parameter shows good reproducibility on a regional basis with a median
      coefficient of variation of 6.5% in healthy volunteers and 12.4% in COPD
      patients. Significant regional differences of lung function parameters derived
      from localized CSSR were found in healthy volunteers and correlations with
      spirometric indices were found. CONCLUSION: Localized 129 Xe CSSR provides
      reproducible estimates of alveolar wall thickness and is able to detect regional
      differences of lung microstructure.

PMID- 30198114
TI  - Earth-Abundant Transition-Metal-Based Electrocatalysts for Water Electrolysis to
      Produce Renewable Hydrogen.
AB  - Fundamentals of water electrolysis, and recent research progress and trends in
      the development of earth-abundant first-row transition-metal (Mn, Fe, Co, Ni, Cu)
      based oxygen evolution reaction (OER) and hydrogen evolution (HER)
      electrocatalysts working in acidic, alkaline, or neutral conditions are reviewed.
      The HER catalysts include mainly metal chalcogenides, metal phosphides, metal
      nitrides, and metal carbides. As for the OER catalysts, the basic principles of
      the OER catalysts in alkaline, acidic, and neutral media are introduced, followed
      by the review and discussion of the Ni, Co, Fe, Mn, and perovskite-type OER
      catalysts developed so far. The different design principles of the OER catalysts
      in photoelectrocatalysis and photocatalysis systems are also presented. Finally,
      the future research directions of electrocatalysts for water splitting, and
      coupling of photovoltaic (PV) panel with a water electrolyzer, so called PV-E,
      are given as perspectives.

PMID- 30198115
TI  - Compressed-Sensing MP2RAGE sequence: Application to the detection of brain
      metastases in mice at 7T.
AB  - PURPOSE: To develop a Compressed Sensing (CS)-MP2RAGE sequence to drastically
      shorten acquisition duration and then detect and measure the T1 of brain
      metastases in mice at 7 T. METHODS: The encoding trajectory of the standard
      Cartesian MP2RAGE sequence has been modified (1) to obtain a variable density
      Poisson disk under-sampling distribution along the ky -kz plane, and (2) to
      sample the central part of the k-space exactly at TI1 and TI2 inversion times. In
      a prospective study, the accuracy of the T1 measurements was evaluated on
      phantoms containing increasing concentrations of gadolinium. The CS acceleration
      factors were increased to evaluate their influence on the contrast and T1
      measurements of brain metastases in vivo. Finally, the 3D T1 maps were acquired
      with at 4-fold increased spatial resolution. The volumes and T1 values of the
      metastases were measured while using CS to reduce scan time. RESULTS: The
      implementation of the CS-encoding trajectory did not affect the T1 measurements
      in vitro. Accelerating the acquisition by a factor of 2 did not alter the
      contrast or the T1 values of the brain metastases. 3D T1 maps could be obtained
      in < 1 min using a CS factor of 6. Increasing the spatial resolution enabled more
      accurately measurement of the metastasis volumes while maintaining an acquisition
      duration below 5 min. CONCLUSION: The CS-MP2RAGE sequence could be of great
      interest in oncology to either rapidly obtain mouse brain 3D T1 maps or to
      increase the spatial resolution with no penalty on the scan duration.

PMID- 30198116
TI  - Fin healing and regeneration in sturgeon.
AB  - Pectoral fin healing in fin spines and rays were examined in juvenile Atlantic
      sturgeon Acipenser oxyrinchus oxyrinchus following three different sampling
      techniques (n = 8-9 fish per treatment): entire leading fin spine removed, a 1-2
      cm portion removed near the point of articulation, or a 1-2 cm portion removed
      from a secondary fin ray. Also, to determine whether antibiotic treatment
      influences healing, an additional group of fish (n = 8) was not given an
      injection of an oxytetracycline (OTC)-based antibiotic following removal of the
      entire leading fin spine. Following fin sampling, fish from different treatments
      were mixed equally between three large (4,000 I) recirculating systems and fin
      ray healing and mortality were monitored over a 12 month period. To assess
      healing, blood samples were collected at 4 months to measure immune system
      responses, radiographs were taken at 4, 8 and 12 months to assess the degree of
      calcification in regions of damaged fins and fins were analyzed histologically at
      12 months. Fish grew from a mean weight of 1.8 to 3.2 kg during the experiment
      and survival was near 100% in all treatments, with only one fish dying of unknown
      causes. Leukocyte counts, an indication of health status and survival were
      similar among treatments and in groups with or without antibiotic injection.
      Radiographs revealed mineralization took longer in fish with the entire leading
      fin spine removed and was the slowest near the point of articulation, presumably
      due to the greater structural support for the pectoral fin at this location.
      Histological sampling indicated spines and rays had similar healing patterns.
      Following injury, an orderly matrix of collagen bundles and many evenly spaced
      scleroblasts were present, transitioning to Sharpey fibres, with concentric
      layers forming lamellar bone. Healing and mineralization were characterized as
      periosteal osteogenesis and included embedded osteocytes surrounded by an osteoid
      seam. Chondroid formation was apparent in a few fractures not associated with
      treatments. The duration of time for external wound healing and internal
      mineralization of spines and rays depended on the fin treatment, with the slowest
      healing observed in fish with the most tissue removed, the entire leading fin
      spine.

PMID- 30198118
TI  - Telling the truth to young children: Ethical reasons for information disclosure
      in paediatrics.
AB  - When parents ask doctors not to disclose certain information to a child, doctors
      are challenged to articulate ethical reasons for giving information to children.
      This paper maps out the professional and legal landscape in which information
      giving to children is taking place and identifies the key ethical arguments that
      have been made for disclosure of information to the child patient. We focus on
      pre-adolescent children, who have not reached a developmental stage that would
      see them regarded as 'mature minors'. While doctors can be relatively certain
      that professional and legal requirements will endorse their disclosure of
      information to the 'mature minor', guidelines are not clear on information-giving
      to pre-adolescents (immature minors). We identify six ethical reasons for telling
      the truth to younger children. It is noteworthy that there are good reasons to
      tell the truth to children, which are independent of any question of the child's
      capacity to be involved in decision-making.

PMID- 30198119
TI  - A 21st century plague of biblical proportions.
AB  - Modern medicine has eradicated smallpox, contained polio and is making
      significant advances in personalised/genetic medicine. However, we are facing a
      pandemic of apocalyptic proportions, and there is currently no vaccine or United
      Nations Charter to help address this issue. Following its insidious spread in the
      1980s, the full impact of this phenomenon on civilisation has not been fully
      appreciated. It has slipped under the radar of the International Classification
      of Diseases (ICD-10) and Diagnostic and Statistical Manual of Mental Disorders
      (DSM-5) classification systems. We all know someone who is affected by this
      condition, and society is struggling to cope with the acute and chronic morbidity
      that has ensued. I am, of course, referring to the problem of the workplace
      email. This article examines the problems associated with workplace email and
      aims to offer some strategies to help contain it.

PMID- 30198117
TI  - Properties Design: Prediction and Experimental Validation of the Luminescence
      Properties of a New EuII -Based Phosphor.
AB  - A theoretical model that allows to predict, for the first time, the luminescence
      properties of a new phosphor (BaSnSi3 O9 :Eu2+ ) is presented. The predicted
      emission wavelength, 488 nm with a 64 nm bandwidth, was confirmed by subsequent
      experimental work. The method consists in a multi-electron Hamiltonian
      parametrized from ab initio calculations. The luminescence properties of other
      similar compounds (i.e., BaHfSi3 O9 :Eu2+ and BaZrSi3 O9 :Eu2+ ), for which there
      is already experimental information, were also correctly reproduced.

PMID- 30198120
TI  - "Becoming the man you always wanted to be": Exploring the representation of
      health and masculinity in Men's Health magazine.
AB  - ISSUE ADDRESSED: Men's health and lifestyle magazines are a popular medium
      through which hegemonic ideals of masculinity are displayed, influencing the way
      men behave and think about health (Crawshaw, 2007, Soc Sci Med, 65, 1606; Stibbe,
      2004, Men Masc, 7, 31). METHODS: This study conducted a critical discourse
      analysis of Australia's most popular men's health and lifestyle magazine, Men's
      Health, in order to understand how health is presented to men. Six issues were
      examined, from April 2016 to September 2016. RESULTS: Three themes supporting
      hegemonic masculine discourses were revealed: a forged physique, (hetero)sexual
      prowess and career dominance. A fourth theme, the new man, was also identified
      revealing a shift in attitudes towards nutrition and style. CONCLUSIONS: Despite
      this shift in the representation of masculinity, hegemonic ideals remain dominant
      in the construction of Australian masculinity in this popular men's health and
      lifestyle magazine. SO WHAT?: This study highlights the utility of Men's Health
      magazine in promoting health and brings into question whether the current
      representation of masculinity works towards improving or decreasing the health of
      Australian men.

PMID- 30198122
TI  - Neutrophilic fixed drug eruption: a mimic of neutrophilic dermatoses.

PMID- 30198121
TI  - Determination of the dose rate constant through Monte Carlo simulations with
      voxel phantoms.
AB  - PURPOSE: The main goal of this study was to determine the dose rate constant of
      radionuclides used in Nuclear Medicine when they are biodistributed in humans.
      The secondary goal was to calculate the effective half-life for the same
      radionuclides in order to determine the realistic dose due to the incorporation
      of these nuclides for a variety of reasons. METHODS: Anthropomorphic voxel
      phantoms, with characteristics based on ICRP-110 were considered and the
      biodistributions of radionuclides were simulated using the Monte Carlo code
      MCNPX. In addition, the effective half-lives for all simulated radionuclides were
      calculated. RESULTS: The results for the dose rate constant, taking into account
      the patient body attenuation, showed no correlation between the biodistribution
      of the radionuclide and the energy of the radiation emitted. Body attenuation
      ranged between 6.7% and 94.1%. Also, the priority angle of radiation emission was
      determined. The values found for the body attenuation agree with the literature,
      corroborating the calculation of the body dose rate constant. CONCLUSIONS: The
      results for the body dose rate constant calculated in this work, for 30
      radionuclides and 57 radiopharmaceuticals, and their effective half-lives, may be
      used to estimate the dose emitted by a person who has incorporated a radionuclide
      in the Nuclear Medicine activity range. This dose will be optimized when the body
      dose rate constant and the effective half-life determined in this study are used
      together with dose reduction factors.

PMID- 30198123
TI  - Occurrence and subtype distribution of Blastocystis sp. in humans, dogs and cats
      sharing household in northern Spain and assessment of zoonotic transmission risk.
AB  - Blastocystis sp. is probably the most common enteric parasite in humans globally.
      Although the role of Blastocystis in human disease is still controversial,
      epidemiological and experimental evidence suggests that pathogenicity may be
      associated with certain subtypes of the protist. Since the life cycle of
      Blastocystis is maintained through still elusive pathways, companion animals have
      attracted the attention of researchers as potential reservoirs of human
      infections. In order to evaluate the risk of zoonotic transmission of
      Blastocystis, we investigated the occurrence and molecular diversity of this
      microorganism in human, canine and feline populations sharing temporal and
      spatial settings in the province of Alava, northern Spain. A total of 268
      (including 179 human, 55 canine and 34 feline) faecal specimens were obtained
      from 63 family households during February-December 2014. Detection of
      Blastocystis was achieved by PCR amplification and sequencing of small subunit
      rRNA genes. Blastocystis was found in 35.2% (95% CI: 0.29%-0.42%) of the human
      stool samples analysed, but not in any of the canine or feline faecal specimens
      investigated. Out of the 63 PCR-positive human samples, 84.1% (53/63) were
      successfully subtyped, allowing the identification of the subtypes ST2 (62.3%),
      ST3 (17.0%), ST1 (13.2%) and ST4 (7.5%). No mixed subtype infections were
      identified. Blastocystis carriage was independent of the gender and region of
      origin of the affected individuals, but children in the age groups of >5-10 years
      and >10-15 years were significantly more affected by the protist. None of the
      risk factors considered (water-use practices, contact with livestock, contact
      with individual undergoing diarrhoeal episodes) were associated with increased
      prevalence of Blastocystis. Our data demonstrate that pet dogs and cats play a
      negligible role as natural reservoirs of human Blastocystis infection in this
      geographic region, although the applicability of these results should be
      corroborated in future molecular epidemiological studies.

PMID- 30198125
TI  - Periodontal complications with age.
AB  - The present literature review on periodontal complications in aging focuses on
      the diagnosis, etiology and development of periodontal complications as a
      complete entity. In addition, the review also focuses on some of the common
      systemic diseases that either may further add to periodontal complications or, as
      result of anti-inflammatory treatment, limit the expression of periodontal
      disease. There is no evidence to suggest that clinical methods to provide
      periodontal therapies have been developed especially for older individuals. There
      is evidence that aging can be associated with periodontally healthy conditions
      through life and with a high level of tooth retention and function. Periodontal
      complications that are difficult to manage are usually associated with concurrent
      medical diseases and complications, or with socio-economic factors that limit the
      ability to provide dental care for the aging population. Currently, some systemic
      medical conditions are managed with anti-inflammatory medications with positive
      effects, while slowing the progression and expression of chronic periodontitis.
      The lack of data from clinical studies on how to manage periodontal complications
      in aging is obvious.

PMID- 30198124
TI  - Hyperpolarized 13 C spectroscopic imaging using single-shot 3D sequences with
      unpaired adiabatic refocusing pulses.
AB  - Hyperpolarized MRI with 13 C-labeled metabolites has enabled metabolic imaging of
      tumors in vivo. The heterogeneous nature of tumors and the limited lifetime of
      the hyperpolarization require high resolution, both temporally and spatially. We
      describe two sequences that make more efficient use of the 13 C polarization than
      previously described single-shot 3D sequences. With these sequences, the target
      metabolite resonances were excited using spectral-spatial pulses and the data
      acquired using spiral readouts from a series of echoes created using a fast-spin
      echo sequence employing adiabatic 180 degrees  pulses. The third dimension was
      encoded with blipped gradients applied in an interleaved order to the echo train.
      Adiabatic inversion pulses applied in the absence of slice selection gradients
      allowed acquisition of signal from odd echoes, formed by unpaired adiabatic
      pulses, as well as from even echoes. The sequences were tested on tumor-bearing
      mice following intravenous injection of hyperpolarized [1-13 C]pyruvate. [1-13 C]
      pyruvate and [1-13 C] lactate images were acquired in vivo with a 4 * 4 * 2 cm3
      field of view and a 32 * 32 * 16 matrix, leading to a nominal resolution of 1.25
      * 1.25 * 1.25 mm3 and an effective resolution of 1.25 * 1.25 * 4.5 mm3 when the z
      direction point spread function was taken into account. The acquisition of signal
      from more echoes also allowed for an improvement in the signal-to-noise ratio for
      resonances with longer T2 relaxation times. The pulse sequences described here
      produced hyperpolarized 13 C images with improved resolution and signal-to-noise
      ratio when compared with similar sequences described previously.

PMID- 30198126
TI  - Stress, allostatic load, and periodontal diseases.
AB  - Psychosocial stress plays an important role in periodontal disease through
      biological and behavioral pathways. In this paper we review studies that examine
      the relationship between stress and periodontal diseases, and discuss the
      different measures used to assess stress. Self-reported measures, such as the
      Perceived Stress Scale and the Stress Appraisal Measure, have traditionally been
      used to assess stress. Frequent and repeated exposure to stressor(s) leads to
      wear and tear of the body's systems, resulting in what is known as allostatic
      load. In recent years, few studies examining the relationship between stress and
      periodontal diseases have used an aggregate variable, including primary and
      secondary markers of allostatic load, as a biological marker of stress. While
      research on the relationship between allostatic load and periodontal disease is
      still developing, as most of the studies used cross-sectional data, this line of
      research presents a good opportunity for establishing a composite biological
      indicator as a risk factor for periodontal disease. Such an indicator is also
      potentially beneficial for personalized periodontics as it will help to target
      intervention to specific levels of risk and will help in integrating oral and
      general health promotion policies.

PMID- 30198127
TI  - Effect of micronutrient malnutrition on periodontal disease and periodontal
      therapy.
AB  - Periodontitis is a complex chronic inflammatory noncommunicable disease,
      initiated by the development of a dysbiotic microbial plaque biofilm below the
      gingival margin. Whilst the pathogenic biofilm is a "necessary cause" of
      periodontitis, it is insufficient on its own to cause the disease, and a
      destructive immune-inflammatory response is a key to the translation of risk to
      destructive events. Other exposures or "component causes" include individual
      genetic predisposition, lifestyle (including smoking and nutrition), and
      environmental factors. Dietary nutrients are essential for life as they provide
      crucial energy sources in the form of macronutrients, as well as important
      cofactors in the form of micronutrients, which regulate the functionality of
      enzymes during the regulation of anabolic and catabolic processes in human cells.
      Moreover, micronutrients can regulate gene transcription factors, such as the
      proinflammatory nuclear factor kappa B and the anti-inflammatory nuclear factor
      (erythroid-derived 2)-like 2. This review focuses on the role of vitamins
      (vitamin A, carotenoids, the vitamin B complex, vitamins C, D, and E, and
      coenzyme Q10) and minerals (calcium, magnesium, iron, zinc, potassium, copper,
      manganese, and selenium) in human physiology and the impact of their deficiencies
      upon periodontal health and disease.

PMID- 30198128
TI  - Role of periodontal therapy in management of common complex systemic diseases and
      conditions: An update.
AB  - The goal of this review is to summarize the results of randomized trials reported
      since 2010 that assessed the effect of periodontal interventions on at least one
      systemic outcome in human subjects of any age, gender or ethnicity. Oral outcome
      measures included gingivitis, pocket depth, clinical attachment loss and/or
      radiographic bone loss and oral hygiene indices. Studies were excluded if the
      trial was not completed or if treatment was not randomized. The results suggest
      that nonsurgical periodontal intervention provided to pregnant women is safe and
      improves periodontal status without preventing adverse pregnancy outcomes.
      Nonsurgical periodontal intervention was also found to provide modest improvement
      in glycemic control in individuals with type 2 diabetes mellitus and
      periodontitis. Also, improving oral care through mechanical or chemical control
      of dental-plaque biofilm formation can contribute to the prevention of
      respiratory infections in differing clinical settings, including hospitals and
      nursing homes, and in patients with chronic obstructive pulmonary disease. No
      clinical trials were reported that tested the effect of periodontal interventions
      on medical outcomes of atherosclerosis, cardiovascular diseases, stroke,
      rheumatoid arthritis, Alzheimer's disease, chronic kidney disease or malignant
      neoplasia.

PMID- 30198129
TI  - Lifestyle and periodontitis: The emergence of personalized periodontics.
AB  - Personalized medicine is a medical model that involves the tailoring of
      healthcare - with medical decisions, practices, and/or products being customized
      to an individual patient. In this model, diagnostic testing is often employed for
      selecting appropriate and optimal therapies based on the context of a patient's
      genetic content or other epidemiologic, sociologic, molecular, physiologic, or
      cellular analyses. With the advent of major advances in periodontal medicine,
      including genomic discoveries and greater understanding of the multifactorial
      nature of periodontitis, it seems that the time is ripe to use personalized
      medicine as a model for personalized periodontics. This volume of Periodontology
      2000 explores how new advances in our understanding of periodontitis within a
      medical model can evolve into new treatment strategies tailor-made for individual
      patients and not merely based on wholesale treatment paradigms.

PMID- 30198130
TI  - Genetics of periodontitis: Discovery, biology, and clinical impact.
AB  - This review provides an update on genome-wide association studies in
      periodontitis. Studies in populations with European ancestry have dominated the
      landscape of periodontitis genetics studies but, increasingly, studies in Asian
      populations are being reported. The review also summarizes evidence for suggested
      associated genetic variations. The loci associated with genome-wide association
      studies consist of noncoding variations, many of which are predicted to modulate
      levels of gene expression. In this article, the biological functions of the genes
      that are nearest to the associations and their implications for disease etiology
      are also examined. A major challenge in the genetics of periodontitis is
      identification of the causal variant(s) underlying associations with
      periodontitis, elucidation of the molecular mechanisms that are potentially
      affected by the associated variants, and understanding how they contribute to
      disease phenotypes and traits. This will allow emerging medical initiatives to
      make clinical use of genetic discoveries. Large collaborative studies, across
      research centers and across subspecialties and disciplines, will be required to
      realize the promise of genetic discovery in periodontitis.

PMID- 30198131
TI  - Behavioral models for periodontal health and disease.
AB  - The oral health-related behavior of patients with periodontal disease is a
      critical determinant of their health. Psychological models of behavior provide a
      framework for the design of interventions to enhance oral health-related
      behavior. This article reviews published manuscripts on interventions to enhance
      oral health-related behavior, classifying the nature of the interventions
      according to current psychological models of behavior. Fifteen manuscripts
      reporting the findings of 14 studies were identified and reviewed. The present
      article concludes that, based on current evidence, the key elements of effective
      interventions are: goal setting, planning the behavior change, and self
      monitoring.

PMID- 30198133
TI  - Targeting epigenetic mechanisms in periodontal diseases.
AB  - Epigenetic factors are heritable genome modifications that potentially impact
      gene transcription, contributing to disease states. Epigenetic marks play an
      important role in chronic inflammatory conditions, as observed in periodontal
      diseases, by allowing microbial persistence or by permitting microbial insult to
      play a role in the so-called 'hit-and-run' infectious mechanism, leading to
      lasting pathogen interference with the host genome. Epigenetics also affects the
      health sciences by providing a dynamic mechanistic framework to explain the way
      in which environmental and behavioral factors interact with the genome to alter
      disease risk. In this article we review current knowledge of epigenome regulation
      in light of the multifactorial nature of periodontal diseases. We discuss
      epigenetic tagging in identified genes, and consider the potential implications
      of epigenetic changes on host-microbiome dynamics in chronic inflammatory states
      and in response to environmental stressors. The most recent advances in genomic
      technologies have placed us in a position to analyze interaction effects (eg,
      between periodontal disease and type 2 diabetes mellitus), which can be
      investigated through epigenome-wide association analysis. Finally, because of the
      individualized traits of epigenetic biomarkers, pharmacoepigenomic perspectives
      are also considered as potentially novel therapeutic approaches for improving
      periodontal disease status.

PMID- 30198134
TI  - Periodontal complications of hyperglycemia/diabetes mellitus: Epidemiologic
      complexity and clinical challenge.
AB  - This report provides a comprehensive overview of the adverse effects of
      hyperglycemia on the periodontium. It combines data from literature reviews of
      original data from two large, population-based epidemiologic studies with
      comprehensive periodontal health assessment. Emphasis is placed on the
      exploration of hitherto sparsely reported effects of prediabetes and poorly
      controlled (uncontrolled) diabetes, in contrast to the umbrella term "diabetes."
      This stems from the realization that it is not simply having a diagnosis of
      diabetes that may adversely affect periodontal health. Rather, it is the level
      (severity) of hyperglycemia that is the determining factor, not the case
      definition of the diagnosis of diabetes or the type of diabetes in question.
      Importantly, based on existing evidence this paper also attempts to estimate the
      improvements in periodontal probing depth and clinical attachment level that can
      be expected upon successful nonsurgical periodontal treatment in people with
      chronic periodontitis, with and without diabetes, respectively. This exploration
      includes the implentation of new systematic reviews and meta-analyses that allow
      comparison of such intervention outcomes between hyperglycemic and normoglycemic
      subjects. Based on both existing literature and original analyses of population
      based studies, we try to answer questions such as: Is there a glycated hemoglobin
      concentration threshold for periodontitis risk? Does short-term periodontal
      probing depth reduction and clinical attachment level gain after scaling and root
      planing depend on glycemic control in type 2 diabetes? Are short-term scaling and
      root planing outcomes in people with hyperglycemia/diabetes inferior to those in
      people without diabetes? Do periodontitis patients with diabetes benefit more
      from the use of adjuvant antibiotics with nonsurgical periodontal treatment than
      people without diabetes? Does hyperglycemia lead to greater tooth loss in
      patients in long-term post-periodontal treatment maintenance programs? Throughout
      this review, we compare our new findings with previous data and report whether
      the results of these new analyses corroborate, or are in discord with, similar
      scientific reports in the literature. We also explore the potential role of
      dental health-care professionals in helping patients control the risk factors
      that are identical for periodontitis and diabetes. Finally, we suggest various
      topics that still need exploration in future research.

PMID- 30198135
TI  - A public health perspective on personalized periodontics.
AB  - In this paper, we consider personalized periodontics from a public health
      perspective. Periodontitis is an under-acknowledged and important public health
      problem, and there has long been interest in identifying and treating those who
      are at high risk of developing this disease. Although susceptibility/risk
      assessment tools in periodontology are currently in their early stages of
      development, personalized periodontics is increasingly becoming a realistic
      approach. At the population level, however, personalized periodontics is not an
      effective way of improving periodontal health because it would target only those
      who seek help or are able to access care. The occurrence of periodontitis in
      populations is socially patterned, with those of lower socio-economic position
      having poorer periodontal health and being far less likely to seek care. There is
      the potential for social inequalities actually to worsen as a result of
      personalized periodontics. In most health systems, personalized periodontics is
      likely to be accessible only to the social strata for whom it is affordable, and
      those with the greatest need for such an intervention will remain the least
      likely to be able to get it. Thus, personalized periodontics is likely to be a
      niche service for a small proportion of the adult population. This is at odds
      with the public health approach.

PMID- 30198136
TI  - Periodontal complications with obesity.
AB  - The purpose of this paper was to identify and summarize current evidence
      describing periodontal complications associated with obesity. Electronic searches
      supplemented with manual searches were carried out to identify relevant
      systematic reviews. Identification, screening, eligibility, and inclusion of
      studies were performed independently by two reviewers. A MeaSurement Tool to
      Assess systematic Reviews (AMSTAR) was used to assess the quality and risk of
      bias of the included reviews. From 430 titles and abstracts screened, 14
      systematic reviews were considered as eligible for inclusion in this meta-review.
      Eight reviews reported on cross-sectional studies investigating the association
      of obesity and periodontal diseases, 4 included longitudinal studies, 5 addressed
      response to periodontal therapy, 5 reported on studies investigating biomarkers,
      and only 2 were related to pediatric population samples. Systematic review
      summaries in the various study design domains (cross-sectional, longitudinal and
      experimental) report that obese individuals are more likely to have periodontal
      diseases, with more severe periodontal conditions, than nonobese individuals,
      with cross-sectional evidence congruent with longitudinal studies showing that
      obesity or weight gain increases the risk of periodontitis onset and progression.
      Published research on the effect of obesity on responses to periodontal therapy,
      or systemic or local biomarkers of inflammation, is variable and therefore
      inconclusive based on the evidence currently available, which suggests that
      overweight/obesity contributes to periodontal complications independently of
      other risk factors, such as age, gender, smoking, or ethnicity. This evidence
      supports the need for risk assessments for individual patients to facilitate
      personalized approaches in order to prevent and treat periodontal diseases.

PMID- 30198137
TI  - Periodontal complications of prescription and recreational drugs.
AB  - Drug use for both therapeutic and recreational purposes is very widespread in
      most societies. The range of drugs used, the variations in response to these
      drugs and other health and behavioral confounders mean that drug use may be an
      important contributor to individualized periodontal diagnoses. In this narrative
      review, we review the main reported effects of drugs on the periodontal tissues
      and periodontal disease processes. Although some of the more common adverse drug
      reactions on periodontal tissues are well described, in many other cases the
      evidence for these drug effects is quite limited and based on small case series
      or isolated reports. Prescription drugs are responsible for a range of effects,
      including drug-induced gingival overgrowth and increased gingival bleeding, and
      influence periodontal inflammation and periodontal breakdown. The effects of
      recreational drugs on the periodontal tissues is less well researched, perhaps
      for the obvious reason that assembling large cohorts of recreational drug users
      presents particular challenges. Use of nearly all of these substances is
      associated with poorer periodontal and dental health, although there is almost
      certainly a large degree of behavioral confounding in these findings. Overall,
      further studies of adverse drug reactions on the periodontal tissues are required
      as this continues to be an important and increasing factor in periodontal health
      determination.

PMID- 30198132
TI  - Personalized periodontal treatment for the tobacco- and alcohol-using patient.
AB  - The use of various forms of tobacco is one of the most important preventable risk
      factors for the incidence and progression of periodontal disease. Tobacco use
      negatively affects treatment outcomes for both periodontal diseases and
      conditions, and for dental implants. Tobacco-cessation programs can mitigate
      these adverse dental treatment outcomes and may be the most effective component
      of a personalized periodontal treatment approach. In addition, heavy alcohol
      consumption may exacerbate the adverse effects of tobacco use. In this review,
      the microbiology, host/inflammatory responses and genetic characteristics of the
      tobacco-using patient are presented as a framework to aid the practitioner in
      developing personalized treatment strategies for these patients. These
      personalized approaches can be used for patients who use a variety of tobacco
      products, including cigarettes, cigars, pipes, smokeless tobacco products, e
      cigarettes and other tobacco forms, as well as patients who consume large amounts
      of alcohol. In addition, principles for developing personalized tobacco-cessation
      programs, using both traditional and newer motivational and pharmacological
      approaches, are presented.

PMID- 30198138
TI  - Contemporary approaches for identifying individual risk for periodontitis.
AB  - Key breakthroughs in our understanding of the etiology and principles of
      predictable treatment of patients with chronic periodontitis first emerged in the
      late 1960s and carried on into the mid-1980s. Unfortunately, some generalizations
      of the evidence led many to believe that periodontitis was a predictable result
      of exposure to bacterial plaque accumulations over time. For a brief period, the
      initial plaque concept was translated by some to implicate specific bacterial
      infections, with both concepts (plaque exposure and specific infection) being
      false assumptions that led to clinical outcomes which were frustrating to both
      the clinician and the patient. The primary misconceptions were that every
      individual was equally susceptible to periodontitis, that disease severity was a
      simple function of magnitude of bacterial exposure over time, and that all
      patients would respond predictably if treated based on the key principles of
      bacterial reduction and regular maintenance care. We now know that although
      bacteria are an essential initiating factor, the clinical severity of
      periodontitis is a complex multifactorial host response to the microbial
      challenge. The complexity comes from the permutations of different factors that
      may interact to alter a single individual's host response to challenge,
      inflammation resolution and repair, and overall outcome to therapy. Fortunately,
      although there are many permutations that may influence host response and repair,
      the pathophysiology of chronic periodontitis is generally limited to mild
      periodontitis with isolated moderate disease in most individuals. However,
      approximately 20%-25% of individuals will develop generalized severe
      periodontitis and probably require more intensive bacterial reduction and
      different approaches to host modulation of the inflammatory outcomes. This latter
      group may also have serious systemic implications of their periodontitis. The
      time appears to be appropriate to use what we know and currently understand to
      change our approach to clinical care. Our goal would be to increase our
      likelihood of identifying those patients who have a more biologically disruptive
      response combined with a more impactful microbial dysbiosis. Current evidence,
      albeit limited, indicates that for those individuals we should prevent and treat
      more intensively. This paper discusses what we know and how we might use that
      information to start individualizing risk and treat some of our patients in a
      more targeted manner. In my opinion, we are further along than many realize, but
      we have a great lack of prospective clinical evidence that must be accumulated
      while we continue to unravel the contributions of specific mechanisms.

PMID- 30198139
TI  - Questioning "choice": A multinational metasynthesis of research on directly
      funded home-care programs for older people.
AB  - In many developed contexts, home-care services have been overhauled with the
      intent of increasing control and flexibility for those using social and health
      services. This change is associated with providing funds directly to individuals,
      and sometimes their families and supports, to arrange at home-care assistance
      with the activities of daily living. Directly funded home-care programs, or
      "direct funding" (DF), are not value-neutral policy interventions, but complex
      and politicised tools for the enactment of care in contemporary times. In this
      qualitative metasynthesis, we consider 47 research articles published between
      2009 and 2017 that explore various DF programs for older persons in the United
      Kingdom, Australia, and the United States to identify core concepts in the
      literature. We find that choice emerges as a central concern. We then assess the
      literature to explore the questions: How does the existing literature
      conceptualise choice, and the mechanisms through which choice is enhanced, in DF
      programs for older persons? How is choice, and the benefit of choice to older
      service users, understood in relevant studies? We argue that the concept of
      "choice" manifests as a normative goal with presumed benefits among the studies
      reviewed. Particularly when discussing DF for older people, however, it is
      essential to consider which mechanisms improve care outcomes, rather than
      focusing on which mechanisms increase choice writ large. In the case of DF,
      increased choice comes with increased legal responsibilities and often
      administrative tasks that many older people and their supports find burdensome.
      Furthermore, there is no evidence that choice over all elements of one's services
      is the mechanism that improves care experiences. We conclude by presenting
      alternative models of understanding care emerging from feminist and other
      critical scholarship to consider if we are, perhaps, asking the wrong questions
      about why DF is so often preferred over conventional home-care delivery.

PMID- 30198140
TI  - Vitamin D and folate: A reciprocal environmental association based on seasonality
      and genetic disposition.
AB  - OBJECTIVES: The purpose of this study was (1) to elucidate any reciprocal
      seasonal relationship that might exist between red cell folate (RCF) and serum
      vitamin D3 Levels; (2) to explore whether folate-related gene variants that
      influence/alter DNA-thymidylate and methyl group biosynthesis modify any
      associations detected in objective 1; and (3) to consider whether these processes
      might influence reproductive success consistent with the "folate-vitamin D-UV
      hypothesis of skin pigmentation" evolutionary model. METHODS: A large (n = 649)
      Australian cross-sectional study population was examined. Polymerase chain
      reaction (PCR)/Restriction fragment length polymorphism (RFLP) analysis was used
      to genotype C677T-MTHFR, C1420T-SHMT, T401C-MTHFD and 2R > 3R-TS. RCF was
      measured by chemiluminescent immunoassay and vitamin D2 and D3 by HPLC. RESULTS:
      RCF and photosynthesized vitamin D3 , but not RCF and dietary vitamin D2 ,
      exhibit a significant reciprocal association in spring and summer. Three folate
      genes (C677T-MTHFR, C1420T-SHMT, and 2R > 3R-TS) strengthen this effect in
      spring, and another (T401C-MTHFD) in summer. Effects are seasonal, and do not
      occur over the whole year. CONCLUSIONS: Findings are consistent with what might
      be required for the "folate-vitamin D-UV hypothesis of skin pigmentation" model.
      It suggests genetic influence in provision of one-carbon units by 5,10-methylene
      H4 folate, may be an important factor in what appears to be a clear seasonal
      relationship between vitamin D3 and folate status.

PMID- 30198141
TI  - Proton pump inhibitor therapy does not increase serum endotoxin activity in
      patients with cirrhosis.
AB  - AIM: Proton pump inhibitors (PPIs) are frequently prescribed in patients with
      cirrhosis, but this therapy entails potential complications. We aimed to
      investigate the influence of PPI use on intestinal permeability in patients with
      cirrhosis. METHODS: We recruited 228 patients with cirrhosis and divided them
      into four groups. Group (Gp)1 comprised patients receiving a PPI with concurrent
      neomycin (NEO) (PPI-NEO group, n = 14 [6.1%]), Gp2 and Gp3 comprised those
      receiving either PPI or NEO (PPI group, n = 91 [39.9%]; and NEO group, n = 11
      [4.4%]), and Gp4 comprised those receiving neither of these medications (control
      group; n = 112 [49.1%]). We assessed the intestinal permeability by measuring
      endotoxin activity (EA) using a luminol chemiluminescence method. RESULTS:
      Endotoxin activity levels were significantly higher in patients with Child B
      cirrhosis than in those with Child A cirrhosis, but we found no significant
      differences in EA levels between patients with Child C cirrhosis and those with
      either Child A or B cirrhosis. We observed no significant differences in EA
      levels among groups 1-4. Patients without antibiotic exposure (n = 203),
      comprising 91 patients on PPI therapy (Gp2) and 112 no-PPI-therapy controls
      (Gp4), were subdivided according to Child-Pugh (CP) classification. We found no
      significant differences in EA levels between Gp2 and Gp4 in either CP class.
      CONCLUSION: Our results suggest that PPI usage does not have a significant impact
      on serum levels of gut-derived endotoxins, which are already elevated because of
      the increased intestinal permeability in patients with cirrhosis.

PMID- 30198142
TI  - Obsessive-compulsive symptomatology in female adolescent inpatients with
      restrictive compared with binge-purge eating disorders.
AB  - OBJECTIVE: Strong relationships exist between obsessive-compulsive (OC) disorder
      and eating disorders (EDs). The aim of the study was to investigate whether OC
      symptoms would be expressed differently in different ED types. METHOD: Ninety
      four female adolescent inpatients with restricting anorexia nervosa (AN-R), 67
      with binge/purge AN (AN-B/P), and 48 with bulimia nervosa (BN) were assessed on
      admission and discharge using the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS),
      Yale-Brown-Cornell Eating Disorders Scale (YBC-EDS), Eating Attitude Test-26 (EAT
      26), Beck Depression Inventory (BDI), and State-Trait Anxiety Inventory (STAI).
      RESULTS: On admission, patients with AN-B/P exhibited higher scores on the Y
      BOCS, YBC-EDS, EAT-26, and BDI in comparison with patients with AN-R or BN. A
      significant improvement on all psychometric variables from admission to discharge
      was found for all participants taken together. Nonetheless, patients with AN-B/P
      and/or BN showed a greater improvement on Y-BOCS, BDI, and STAI than patients
      with AN-R, whereas no between-group difference was found for YBC-EDS and EAT-26.
      CONCLUSIONS: Obsessionality is more severe in acutely ill AN-B/P patients than in
      patients with AN-R and BN, whereas a greater improvement in obsessionality from
      the acutely ill to the stabilized ED condition is found in patients with
      binge/purge in comparison with restrictive pathology.

PMID- 30198143
TI  - Growth and reproduction of Echeneis naucrates from the eastern Gulf of Mexico.
AB  - This study describes growth and reproductive characteristics of a facultative
      elasmobranch symbiont, Echeneis naucrates. Females grew slower but achieved a
      larger size than males (growth coefficient, K = 0.25 and 0.38 year-1 , and mean
      maximum size, Linfinity = 603 and 477 mm, respectively). Mean relative batch
      fecundity was 39.5 (s.d. = 13.1). Gonadosomatic indices peaked in July and August
      for males and females, respectively, with histology evidence of readiness to
      spawn or active spawning in August. Host-symbiont length ratios increased
      linearly with sharksucker length (y = 0.0402 + 0.0003x, adjusted R2 = 0.56).

PMID- 30198144
TI  - Photoinduced Palladium-Catalyzed Negishi Cross-Couplings Enabled by the Visible
      Light Absorption of Palladium-Zinc Complexes.
AB  - A visible-light-induced Negishi cross-coupling is enabled by the activation of a
      Pd0 -Zn complex. With this photocatalytic method, the scope of deactivated aryl
      halides that can be employed in the Negishi coupling was significantly expanded.
      NMR experiments conducted in the presence and absence of light confirmed that the
      formation of the palladium-zinc complex is key for accelerating the oxidative
      addition step.

PMID- 30198145
TI  - Serum elafin as a potential inflammatory marker in psoriasis.
AB  - BACKGROUND: Psoriasis is a distressing chronic skin disease. Its exact
      pathogenesis is still unclear, as many factors interplay in its occurrence. AIM:
      The aim of the study is to estimate elafin levels in the serum of both cases and
      controls and to correlate the levels with psoriasis severity and other markers of
      inflammation. SUBJECTS AND METHODS: Twenty-six psoriatic cases along with 26
      healthy controls were assigned in this case-control study. Psoriasis severity was
      determined by Psoriasis Area and Severity Index score. Elafin levels were
      measured by ELISA in serum of both cases and controls. C-reactive protein (CRP)
      and erythrocyte sedimentation rate (ESR) were measured in the cases. RESULTS:
      Elafin levels show highly statistical significance difference (P < 0.001) between
      cases and controls. There is a statistical significant correlation between elafin
      levels and both psoriasis severity and inflammation markers as CRP and ESR.
      CONCLUSION: Elafin represents a mirror for psoriasis severity and inflammatory
      state.

PMID- 30198146
TI  - Thermally Switchable Liquid Crystals Based on Cellulose Nanocrystals with Patchy
      Polymer Grafts.
AB  - A thermally "switchable" liquid-crystalline (LC) phase is observed in aqueous
      suspensions of cellulose nanocrystals (CNCs) featuring patchy grafts of the
      thermoresponsive polymer poly(N-isopropylacrylamide) (PNIPAM). "Patchy" polymer
      decoration of the CNCs is achieved by preferential attachment of an atom transfer
      radical polymerization (ATRP) initiator to the ends of the rods and subsequent
      surface-initiated ATRP. The patchy PNIPAM-grafted CNCs display a higher colloidal
      stability above the lower critical solution temperature (LCST) of PNIPAM than
      CNCs decorated with PNIPAM in a brush-like manner. A 10 wt% suspension of the
      "patchy" PNIPAM-modified CNCs displays birefringence at room temperature,
      indicating the presence of an LC phase. When heated above the LCST of PNIPAM, the
      birefringence disappears, indicating the transition to an isotropic phase. This
      switching is reversible and appears to be driven by the collapse of the PNIPAM
      chains above the LCST, causing a reduction of the rods' packing density and an
      increase in translational and rotational freedom. Suspensions of the "brush"
      PNIPAM-modified CNCs display a different behavior. Heating above the LCST causes
      phase separation, likely because the chain collapse renders the particles more
      hydrophobic. The thermal switching observed for the "patchy" PNIPAM-modified CNCs
      is unprecedented and possibly useful for sensing and smart packaging
      applications.

PMID- 30198147
TI  - Monitoring of cefepime in urine by micellar electrokinetic capillary
      chromatography with ultraviolet detection and liquid chromatography coupled to
      mass spectrometry.
AB  - Cefepime monitoring in urine by micellar electrokinetic capillary chromatography
      with UV detection and liquid chromatography coupled to mass spectrometry via
      electrospray ionization is described. For micellar electrokinetic capillary
      chromatography, sample preparation comprised urine dilution and dodecyl-sulfate
      protein precipitation at pH 4.5, whereas diluted urines were analyzed in the
      other assay. Both approaches provided suitable conditions for cefepime analysis
      in urines of healthy volunteers that were spiked with cefepime. Cefepime
      monitoring by micellar electrokinetic capillary chromatography in samples from
      patients taking multiple drugs were prone to interferences, whereas liquid
      chromatography coupled to mass spectrometry provided clean chromatograms and thus
      selective detection of cefepime in all samples. The latter assay was used to
      measure urinary cefepime in a prospective pilot study and to assess cefepime
      stability in urines at 25, 4, -20 and -70 degrees C. The data suggest that
      urinary cefepime is stable for at least 72 h at all tested temperatures.

PMID- 30198148
TI  - Dynamics of early post-operative plasma ddcfDNA levels in kidney transplantation:
      a single-center pilot study.
AB  - Donor-derived cell-free DNA (ddcfDNA) is reported to be a promising noninvasive
      biomarker for acute rejection in organ transplant. However, studies on monitoring
      ddcfDNA dynamics during the early periods after organ transplantation are scarce.
      Our study assessed the dynamic variation in ddcfDNA in early period with various
      types and status of kidney transplantation. Target region capture sequencing used
      identifies ddcfDNA level in 21 kidney transplant recipients. Median ddcfDNA level
      was 20.69% at the initial time post-transplant, and decreased to 5.22% on the
      first day and stayed at the stable level after the second day. The ddcfDNA level
      in DCD (deceased donors) group (44.99%) was significantly higher than that in
      LDRT (living donor) group (10.24%) at initial time, P < 0.01. DdcfDNA level in
      DGF (delayed graft function) recipients was lower (23.96%) than that in non-DGF
      (47.74%) at the initial time, P = 0.89 (19.34% in DGF and 4.46% in non-DGF on the
      first day, P = 0.17). DdcfDNA level at initial time significantly correlated with
      serum creatinine (r2  = 0.219, P = 0.032) and warm ischemia time (r2  = 0.204, P
      = 0.040). Plasma ddcfDNA level decreased rapidly follow an L-shaped curve post
      transplant, and level in DGF declined slower than non-DGF. The rebound of ddcfDNA
      level may indicate the occurrence of acute rejection.

PMID- 30198149
TI  - Levels of miR-31 and its target genes in dermal mesenchymal cells of patients
      with psoriasis.
AB  - BACKGROUND: Psoriasis is characterized by chronic inflammatory dermatosis, and
      the pathogenesis of psoriasis is associated with mesenchymal stem cells (MSCs)
      and deregulation of the expression of miR-31. This study aimed to clarify the
      function of miR-31 in dermal MSCs (DMSCs) in the pathogenesis of psoriasis.
      METHODS: The expression of miR-31 was assayed by a microarray and that of target
      genes of miR-31 was tested by quantitative PCR. RESULTS: The expression of miR-31
      in the psoriasis group was 0.2677 folds that of the control group. The expression
      of EMP1 and EIG121L genes, whose products are located on the cell membrane, in
      the psoriasis group was 4.095579 and 5.367017 folds that in the control group,
      respectively. The expression of GRB10, PTPN14, QKI, RNF144B, and TACC2 genes,
      whose products are located in the cytoplasm, in the psoriasis group was 1.440428,
      1.198335, 1.737285, 7.379546, and 1.531947 folds that of the control. The
      expression of PRELP, whose products are secreted in the extracellular space, in
      the psoriasis group was 1.351684 folds that of the control. The expression of
      RBMS1, KHDRBS3, and SATB2, whose products play a role in the nucleus, in the
      psoriasis group was 2.237199, 1.277159, and 1.005742 folds that of the control,
      respectively. CONCLUSIONS: Our results suggest that the low expression of miR-31
      in DMSCs in patients with psoriasis causes an increase in the expression of some
      of its target genes, which in turn facilitates T lymphocyte activation by
      inhibiting the proliferation of DMSCs and therefore participates in the
      pathogenesis of psoriasis.

PMID- 30198150
TI  - mRECIST provides insight into tumor biology for patients with hepatocellular
      carcinoma awaiting liver transplantation.
AB  - BACKGROUND: With recent changes in UNOS policy, patients in the United States
      (US) with HCC are likely to spend more time on the liver transplant (LT) waiting
      list. The increasing wait time will allow for an opportunity to assess tumor
      biology prior to LT. Modified Response Evaluation Criteria in Solid Tumors
      (mRECIST) paradigm provides such a framework for this assessment, and yet little
      is understood of its utility as it would apply for patients listed for LT in the
      US. METHODS: Through a collaboration between the UCSF and the Mayo Clinic,
      Florida, the experience of 772 patients listed for LT were retrospectively
      reviewed to study the impact of immediate mRECIST classification following
      locoregional therapy (LRT) on pre- and post- LT outcomes. RESULTS: Patients who
      had progression of disease (PD) (N=72), failed to respond to LRT (N=89) at any
      time point, or did not achieve radiologic complete response (CR) (N=226) were all
      at significant risk for waitlist dropout (OR=12.11, 4.81, and 2.48;
      respectively). CR identified a cohort of patients who were at reduced risk for
      waitlist dropout, however, 24.9% eventually required further intervention while
      waiting for transplant, and as many 81.9% were found to have residual HCC on
      explant pathology. Failure to respond to LRT was associated with increased risk
      for recurrence (OR = 3.00) more so than PD (OR=1.36), suggesting that despite PD
      patients who eventually can respond to LRT may represent favorable candidates for
      LT. CONCLUSIONS: For patients awaiting LT, mRECIST assessment provides critical
      guidance for patient management. While PD portends a poor prognosis, our findings
      suggest that further aggressive LRT should be pursued as response to LRT may
      yield acceptable results for patients awaiting LT as well as post-LT. This
      article is protected by copyright. All rights reserved.

PMID- 30198151
TI  - The rapid A/Ci response: a guide to best practices: A response to Taylor & Long
      (2018) 'Phenotyping photosynthesis on the limit - a critical examination of
      RACiR'.

PMID- 30198152
TI  - Variational data assimilation for transient blood flow simulations: Cerebral
      aneurysms as an illustrative example.
AB  - Several cardiovascular diseases are caused from localised abnormal blood flow
      such as in the case of stenosis or aneurysms. Prevailing theories propose that
      the development is caused by abnormal wall shear stress in focused areas.
      Computational fluid mechanics have arisen as a promising tool for a more precise
      and quantitative analysis, in particular because the anatomy is often readily
      available even by standard imaging techniques such as magnetic resonance and
      computed tomography angiography. However, computational fluid mechanics rely on
      accurate initial and boundary conditions, which are difficult to obtain. In this
      paper, we address the problem of recovering high-resolution information from
      noisy and low-resolution physical measurements of blood flow (for example, from
      phase-contrast magnetic resonance imaging [PC-MRI]) using variational data
      assimilation based on a transient Navier-Stokes model. Numerical experiments are
      performed in both 3D (2D space and time) and 4D (3D space and time) and with
      pulsatile flow relevant for physiological flow in cerebral aneurysms. The results
      demonstrate that, with suitable regularisation, the model accurately reconstructs
      flow, even in the presence of significant noise.

PMID- 30198153
TI  - Analysis of dynamic, bidirectional associations in older adult physical activity
      and sleep quality.
AB  - Sleep quality and physical activity (PA) appear to be interrelated; thus, by
      promoting one behaviour, it may be possible to improve the other in older adults.
      Examination of the within-person day-to-day variation in PA and sleep quality
      could potentially elucidate the directionality of the association of these
      behaviours. We measured sleep quality (i.e. fragmentation, efficiency, duration
      and latency) and moderate-to-vigorous PA using the MotionWatch8(c) over 14
      consecutive days and nights in community-dwelling adults (n = 152; age range 53
      101 years). Multilevel modelling estimated within-subject autoregressive and
      cross-lagged effects and between-subject associations between PA and sleep
      quality. On days when individuals engaged in a high amount of PA on one day
      (relative to their averages), they were more likely to engage in a high amount of
      PA on the next day (estimate, 0.19; 95% CI, 0.14, 0.24). Nights in which
      individuals had a long sleep latency were followed by nights in which they also
      had a long sleep latency (estimate, 0.09; 95% CI, 0.03, 0.14). In contrast,
      nights in which individuals slept for a long period of time were followed by
      nights in which they slept relatively less than their averages (estimate, -0.09;
      95% CI, -0.13, -0.04). When individuals engaged in a large amount of PA during
      the day, they tended to sleep longer that following night (estimate, 0.01; 95%
      CI, 0.001, 0.02). All other associations between PA and sleep quality were not
      significant. Increasing PA therefore might increase sleep duration in older
      adults.

PMID- 30198154
TI  - A review of the use of biostimulants in the vineyard for improved grape and wine
      quality: effects on prevention of grapevine diseases.
AB  - Foliar application of biostimulants (including resistance inducers or elicitors)
      in the vineyard has become an interesting strategy to prevent plant diseases and
      improve grape quality on the grapevine. This also represents a partial
      alternative to soil fertilisation, avoiding some of the negative effects to the
      environment from leaching of nutrients into the groundwater. The foliar
      applications that most promote the synthesis of secondary metabolites in grape
      berries are treatments with nitrogen, elicitors, other biostimulants, and waste
      from the agricultural industry. However, the impact of their use in the vineyard
      depends on a number of conditions, including mainly the type of compound,
      application rate, timing and number of applications, and cultivar. This review
      thus summarises the influence of biostimulants as foliar applications to
      grapevines on grape amino acids and their phenolic and volatile concentrations,
      to define the most important factors in their effectiveness. (c) 2018 Society of
      Chemical Industry.

PMID- 30198155
TI  - Blue light negatively affects the survival of ARPE19 cells through an action on
      their mitochondria and blunted by red light.
AB  - PURPOSE: To ascertain whether red light, known to enhance mitochondrial function,
      can blunt a blue light insult to ARPE19 cells in culture. METHODS: Semi-confluent
      ARPE19 cells cultured in 10% FBS were subjected to various regimes of treatment
      with blue (465-475 nm, 800 lux, 26 W/m2 ) and red (625-635 nm, 950 lux, 6.5 W/m2
      ) light, as well as with toxins that inactivate specific enzymes associated with
      mitochondrial oxidative phosphorylation. Cultures were then analysed for cell
      viability (MTT assay), mitochondrial status (JC-1), ROS formation,
      immunocytochemistry and the activation of specific proteins by
      electrophoresis/Western blotting. In addition, ARPE19 cells were cultured in
      polycarbonate membrane inserts in culture medium containing 1% FBS. Such cultures
      were exposed to cycles of red, blue or a combination of red and blue light for up
      to 6 weeks. Culture medium was changed and the trans-epithelium membrane
      resistance (TER) of the inserts-containing cells was measured twice weekly.
      RESULTS: ARPE19 cells in culture are affected negatively when exposed to blue
      light. This is indicated by a loss of viability, a depolarization of their
      mitochondria and a stimulation of ROS. Moreover, blue light causes an up
      regulation of HO-1 and phospho-p-38-MAPK and a cleavage of apoptosis inhibitory
      factor, proteins which are all known to be activated during cell death. All of
      these negative effects of blue light are significantly blunted by the red light
      administered after the blue light insult in each case. ARPE19 cell loss of
      viability and mitochondrial potential caused by toxins that inhibit specific
      mitochondrial enzyme complexes was additive to an insult delivered by blue light
      in each case. After a time, ARPE19 cells in culture express the tight junction
      protein ZO-1, which is affected by blue light. The development of tight junctions
      between ARPE19 cells grown in inserts reached a steady peak of resistance after
      about 40 days and then increased very slightly over the next 40 days when still
      in darkness. However, maximum resistance was significantly attenuated, when
      cultures were treated with cycles of blue light after the initial 40 days in the
      dark and counteracted significantly when the blue light cycle insult was combined
      with red light. CONCLUSION: Blue light affects mitochondrial function and also
      the development tight junctions between ARPE19 cells, which results in a loss of
      cell viability. Importantly, red light delivered after a blue light insult is
      significantly blunted. These findings argue for the therapeutic use of red light
      as a noninvasive procedure to attenuate insults caused by blue light and other
      insults to retinal pigment epithelial cell mitochondria that are likely to occur
      in age-related macular degeneration.

PMID- 30198156
TI  - Primary cervico-uterine anastomosis in a patient with agenesis of the uterine
      isthmus: A case report and review.
AB  - Arrested caudal extension of the fused Mullerian ducts, either complete or
      segmental, causes obstruction of the outflow tract. We describe a case of
      agenesis of the uterine isthmus and the procedure to establish the continuity of
      the outflow tract. A 15-year-old girl with cyclic pelvic pain and amenorrhea was
      found to have a 3-cm gap between the uterine body and the cervix. After cervico
      uterine anastomosis via laparotomy she menstruated normally and was pain-free.
      Selected cases of arrested Mullerian duct extension can be corrected by primary
      anastomosis, which establishes anatomical continuity and restores menstruation
      and, possibly, future fertility.

PMID- 30198157
TI  - Gamma irradiation of clove: level of trapped radicals and effects on bioactive
      composition.
AB  - BACKGROUND: Food irradiation is a widely used technique for improving the safety
      and shelf life of foods, including most spices. However, growing concerns by
      consumers about this technique require further investigation on the effects of
      radiation, both on the safety of the food and on its organoleptic properties. In
      this work, cloves of diverse origins were submitted to different irradiation
      doses in a 60 Co source. The presence of trapped radicals and their time
      dependent decay after irradiation were assessed by electron spin resonance (ESR)
      spectroscopy. The volatile bioactive composition and the clove oil were evaluated
      before and after irradiation by gas chromatography time-of-flight mass
      spectrometry. RESULTS: Results show an increase of the amount of volatiles
      collected after irradiation, especially of caryophyllene oxide and acetic acid,
      although these are still minor constituents. No new compound was detected after
      irradiation. Radicals decay fast, and 60 days after irradiation they were
      undetectable by ESR. CONCLUSION: Gamma irradiation showed to be a clean technique
      for clove decontamination, since no significant change in the aroma or oil
      compositions was found, and low levels of trapped paramagnetic species, after the
      initial decay period, were detected upon irradiation. Furthermore, irradiation
      doses higher than those legally allowed are equally safe. (c) 2018 Society of
      Chemical Industry.

PMID- 30198158
TI  - Proximal thigh chondrolipoma in a young boy: a rare entity.

PMID- 30198159
TI  - Aqueous Assembly of Zwitterionic Daisy Chains.
AB  - The synthesis and characterization of zwitterionic molecular [c2]- and [a2]-daisy
      chains are described, relying on recognition of a positively charged cyclophane
      and a negatively charged oligo(phenylene-ethynylene) (OPE) rod in aqueous medium.
      For this purpose, syntheses of an acetylene-functionalized macrocyclic receptor
      and a water-soluble OPE-rod as the guest component are presented, from which a
      heteroditopic daisy chain monomer was prepared. This monomer aggregated strongly
      in water/methanol 4:1 and formed molecular daisy chains, which were isolated as
      interlocked species from a stoppering reaction at 1 mm concentration. The cyclic
      dimer [c2] was the main product with an isolated yield of 30 % and consisted of a
      mixture of diastereomers, as evidenced by 1 H NMR spectroscopy.

PMID- 30198160
TI  - Maternal risk factor index and cesarean delivery among women with nulliparous,
      term, singleton, vertex deliveries, Texas, 2015.
AB  - BACKGROUND: Cesarean delivery accounts for over one-third of the ~400 000 annual
      births in Texas, with first-time cesarean accounting for 20% of the overall
      cesareans. We examined associations of maternal medical comorbidities with
      cesarean delivery among nulliparous, term, singleton, vertex (NTSV) deliveries in
      Texas. METHODS: Nulliparous, term, singleton, vertex deliveries to women aged 15
      49 years were identified using the 2015 Texas birth file (Center for Health
      Statistics, Texas Department of State Health Services). A risk factor index was
      constructed (score range 0-4), including preexisting/gestational diabetes
      mellitus, preexisting/gestational hypertension/eclampsia, infertility treatment,
      smoking during pregnancy, and prepregnancy overweight/obesity, and categorized as
      0, 1, 2, and 3+ based on the number of risk factors present. Multivariable
      logistic regression analyses were conducted to examine associations between the
      categorized risk factor index and cesarean delivery, overall and by maternal race
      and ethnicity. RESULTS: Among the 114 535 NTSV deliveries in Texas in 2015, 27.2%
      were by cesarean. The most prevalent maternal risk among all deliveries was
      prepregnancy overweight/obesity (42.4%). The odds of cesarean delivery increased
      significantly with increasing number of risk factors [one risk factor: 1.72 (95%
      CI 1.67-1.78); two risk factors: 2.58 (95% CI 2.46-2.71); and three or more risk
      factors: 3.91 (95% CI 3.45-4.44)]. DISCUSSION: In Texas in 2015, nearly half of
      NTSV deliveries had at least one maternal risk factor and the odds of cesarean
      delivery were significantly elevated for women with a higher risk index score.
      The findings from this study highlight the need for intervening during the
      preconception and interconception period as intrapartum care practices have an
      important influence on birth outcomes.

PMID- 30198161
TI  - Thioflavin T-Amyloid Hybrid Nanostructure for Biocatalytic Photosynthesis.
AB  - Amyloidogenic peptides can self-assemble into highly ordered nanostructures
      consisting of cross beta-sheet-rich networks that exhibit unique physicochemical
      properties and high stability. Light-harvesting amyloid nanofibrils are
      constructed by employing insulin as a building block and thioflavin T (ThT) as a
      amyloid-specific photosensitizer. The ability of the self-assembled amyloid
      scaffold to accommodate and align ThT in high density on its surface allows for
      efficient energy transfer from the chromophores to the catalytic units in a
      similar way to natural photosystems. Insulin nanofibrils significantly enhance
      the photoactivity of ThT by inhibiting nonradiative conformational relaxation
      around the central C?C bonds and narrowing the distance between ThT molecules
      that are bound to the beta-sheet-rich amyloid structure. It is demonstrated that
      the ThT-amyloid hybrid nanostructure is suitable for biocatalytic solar-to
      chemical conversion by integrating the light-harvesting amyloid module (for
      nicotinamide cofactor regeneration) with a redox biocatalytic module (for
      enzymatic reduction).

PMID- 30198162
TI  - Thermally Induced 2D Alloy-Heterostructure Transformation in Quaternary Alloys.
AB  - Composition and phase specific 2D transition metal dichalogenides (2D TMDs) with
      a controlled electronic and chemical structure are essential for future
      electronics. While alloying allows bandgap tunability, heterostructure formation
      creates atomically sharp electronic junctions. Herein, the formation of lateral
      heterostructures from quaternary 2D TMD alloys, by thermal annealing, is
      demonstrated. Phase separation is observed through photoluminescence and Raman
      spectroscopy, and the sharp interface of the lateral heterostructure is examined
      via scanning transmission electron microscopy. The composition-dependent
      transformation is caused by existence of miscibility gap in the quaternary
      alloys. The phase diagram displaying the miscibility gap is obtained from the
      reciprocal solution model based on density functional theory and verified
      experimentally. The experiments show direct evidence of composition-driven
      heterostructure formation in 2D atomic layer systems.

PMID- 30198163
TI  - Placebo effects in adult and adolescent patients with schizophrenia: combined
      analysis of nine RCTs.
AB  - OBJECTIVE: To examine characteristics of placebo responders and seek optimal
      criteria of early improvement with placebo for predicting subsequent placebo
      response in patients with schizophrenia. METHOD: Data of 672 patients with
      schizophrenia randomized to placebo in nine double-blind antipsychotic trials
      were analyzed. Multiple logistic regression analyses were conducted to examine
      associations between placebo response at week 6 (i.e., a >= 25% reduction in the
      Positive and Negative Syndrome Scale [PANSS] score) and gender, age, study
      locations, baseline PANSS total or Marder 5-Factor scores, and per cent PANSS
      score reduction at week 1. Predictive power of improvement at week 1 for
      subsequent response was investigated; sensitivity and specificity of incremental
      5% cutoff points between 5% and 25% reduction in the PANSS total score at week 1
      were calculated. RESULTS: Per cent PANSS total score reduction at week 1 and
      lower PANSS Marder disorganized thought scores at baseline were significantly
      associated with subsequent placebo response. A 10% reduction in a per-protocol
      analysis or a 15% reduction in last-observation-carried-forward analysis in the
      PANSS total score at week 1 showed the highest predictive power. CONCLUSION:
      These findings are informative to identify potential placebo responders at the
      earliest opportunity for optimal trial design for schizophrenia.

PMID- 30198164
TI  - Outcomes of infants born at borderline viability (23-25 weeks gestation) who
      received cardiopulmonary resuscitation at birth.
AB  - AIM: The practice of providing advanced resuscitative measures to infants born at
      borderline viability (23-25+6 weeks gestation) varies among clinicians due to
      perception of futility. The aim of our study was to compare mortality and major
      morbidities in infants born at borderline viability who did not receive
      cardiopulmonary resuscitation (CPR) in the delivery room (No DR-CPR) as compared
      to those who did (DR-CPR). METHODS: A retrospective analysis of prospectively
      collected data of infants born between 23 and 25+6 weeks gestation who were
      resuscitated at birth at the study centre or admitted to neonatal intensive care
      unit from peripheral hospitals, over 8 years (2007-2014). The primary outcome was
      survival, free of disability at 2 years corrected age and secondary outcomes were
      survival at discharge and neonatal morbidities. RESULTS: Of 123 infants in the
      study cohort, 21 received DR-CPR. In unadjusted analysis, there was increased
      mortality rate in the DR-CPR group which was statistically insignificant (26.5
      vs. 42.9%, P = 0.15). After adjustment for potential confounders, there was no
      significant difference in the mortality rate with odds ratio of 1.10 (confidence
      interval: 0.34-3.53, P = 0.86). Among infants who received DR-CPR for >2 min, the
      mortality rate was significantly higher (25.2 vs. 56.3%, P = 0.01). Survival free
      of disability was similar in two groups (50.9 vs. 47.6%, P = 0.78). CONCLUSIONS:
      Among infants born at borderline viability, the vast majority of infants did not
      receive CPR and, if CPR was prolonged for >2 min, mortality was increased. Among
      survivors of the small DR-CPR group, early neurodevelopmental outcomes were
      comparable to the No DR-CPR group.

PMID- 30198165
TI  - Polymer Nanospheres with Hydrophobic Surface Groups as Supramolecular Building
      Blocks Produced by Aqueous PISA.
AB  - A robust and straightforward synthesis of waterborne polymer nanospheres bearing
      the supramolecular association unit dialkoxynapthalene at their surface is
      presented using polymerization-induced self-assembly (PISA). A RAFT agent bearing
      this unit is first employed to produce poly(acrylic acid) chains, which are then
      chain-extended with styrene (S) to spontaneously form the nano-objects via RAFT
      aqueous emulsion polymerization. The particular challenge posed by the
      dialkoxynapthalene hydrophobicity can be overcome by the use of PISA and the
      deprotonation of the poly(acrylic acid). At pH = 7, very homogeneous latexes are
      obtained. The particle diameters can be tuned from 36 to 105 nm (with a narrow
      particle size distribution) by varying the molar mass of the PS block. The
      surface accessibility of the dialkoxynapthalene moieties is demonstrated by
      complexation with the complementary host cyclobis(paraquat-p-phenylene) (CBPQT4+
      . Cl- ), highlighting the potential of the nanospheres to act as building blocks
      for responsive supramolecular structures.

PMID- 30198166
TI  - Omentin-regulated proteins combine a pro-inflammatory phenotype with an anti
      inflammatory counterregulation in human adipocytes: A proteomics analysis.
AB  - AIMS: Experimental and epidemiological studies reported controversial data on the
      role of omentin in type 2 diabetes and cardiovascular diseases. This study aimed
      to characterise the impact of omentin on the secretome of human adipocytes to
      analyse the enrichment of these proteins in metabolic and cellular signalling
      pathways underlying its physiological function. MATERIAL/METHODS: Differentiated
      primary human adipocytes were treated without or with 500 or 2000 ng/mL omentin
      for 24 hours. The secretome was analysed by liquid chromatography coupled tandem
      mass spectrometry. Differences in protein secretion between untreated and omentin
      treated adipocytes were compared using a paired t-test. Other potential upstream
      regulators and the overrepresentation in canonical pathways of omentin-stimulated
      proteins were analysed using Ingenuity Pathway Analysis. RESULTS: The supernatant
      of adipocytes contained 3493 proteins, of which 140 were differentially secreted
      by both concentrations of omentin compared with untreated adipocytes. Among the
      most strongly increased proteins, tumour necrosis factor-inducible gene 6 protein
      (TNFAIP6) was increased by 140-fold in the supernatant. Omentin-regulated
      proteins were overrepresented in seven canonical pathways including eukaryotic
      initiation factor 2 signalling, complement system, and inhibition of matrix
      metalloproteases. We further identified 25 other potential upstream activators of
      omentin-regulated proteins, mainly pro-inflammatory cytokines and transcription
      regulators including NFkappaB. CONCLUSIONS: In differentiated human adipocytes,
      the release of the anti-inflammatory TNFAIP6 might be part of a counterregulatory
      response to the pro-inflammatory action of omentin. Omentin-regulated proteins
      were overrepresented in pathways indicating cellular stress, a pro-inflammatory
      environment and a crosstalk with other organs. Other potential activators of
      omentin-regulated proteins point towards a central role of NFkappaB activation in
      the omentin-induced secretory process.

PMID- 30198167
TI  - Fluid Dynamic Characterization of Transcatheter Aortic Valves Using Particle
      Image Velocimetry.
AB  - Transcatheter aortic valves provide superior systolic hemodynamic performance in
      terms of valvular pressure gradient and effective orifice area compared with
      equivalent size surgical bioprostheses. However, in depth investigation of the
      flow field structures is of interest to examine the flow field characteristics
      and provide experimental evidence necessary for validation of computational
      models. The goal of this study was to compare flow field characteristics of the
      three most commonly used transcatheter and surgical valves using phase-locked
      particle image velocimetry (PIV). 26-mm Edwards SAPIEN 3, 26-mm Medtronic
      CoreValve, and 25-mm Carpentier-Edwards PERIMOUNT Magna were examined in a pulse
      duplicator with input parameters matching ISO-5840, that is, heart rate of 70
      beats/min, cardiac output of 5 L/min, and mean aortic pressure of 100 mm Hg. A 2D
      PIV system was used to obtain flow velocity and viscous shear stress fields
      during the entire cardiac cycle. In vitro testing showed that the mean
      transvalvular pressure gradient was lowest for SAPIEN 3, followed by CoreValve,
      and PERIMOUNT Magna surgical bioprosthesis. In addition, the viscous shear stress
      magnitude within the jet boundary layer was higher in PERIMOUNT Magna than
      CoreValve and SAPIEN 3 at the peak of the flow. However, the measured shear
      stress values were below the known threshold for platelet activation and red
      blood damage. Therefore, shear-induced platelet activation is unlikely to take
      place during systole in the three bioprosthetic heart valves. The PIV
      measurements can be used for verification and validation of computational
      simulations.

PMID- 30198168
TI  - Preservation of microbial DNA in marine sediments: insights from extracellular
      DNA pools.
AB  - Marine sediments harbour extracellular DNA (exDNA) not associated with currently
      living organisms. Including this exDNA in genetic surveys may distort abundance
      and diversity estimates of living prokaryotic communities. We separately extract
      exDNA and intracellular DNA (inDNA) from 11 horizons in a 10-m deep sediment core
      from Aarhus Bay (Denmark) that spans > 9000 years of Holocene sedimentation. We
      compare depth profiles of bacterial and archaeal 16S rRNA gene compositions to
      those of macrofaunal activity (bioturbation), sulfate and methane concentrations,
      sediment age and lithology. Among these variables, bioturbation shows the
      strongest relationship with the two DNA pools. In bioturbated surface sediments,
      the majority of Operational Taxonomic Units (OTUs) present in exDNA is absent
      from inDNA, thus belonging to microorganisms that were not alive at the time of
      sampling. Below the bioturbation zone, the two DNA pools display a much higher
      phylogenetic similarity. At all depths, the majority of exDNA and inDNA sequences
      show highest sequence similarities to sediment microorganisms, a finding that is
      additionally supported by separate analyses on low- and high-molecular weight
      exDNA. Our results indicate that in Aarhus Bay the vast majority of prokaryotic
      exDNA is turned over, thus not contributing to a genetic archive of past
      environmental change.

PMID- 30198169
TI  - Bokeloh bat lyssavirus isolation in a Natterer's bat, Poland.
AB  - In recent years, Bokeloh bat lyssavirus (BBLV), a member of the novel lyssavirus
      genus Bokeloh bat lyssavirus in the family Rhabdoviridae, has been detected in
      Germany (five cases) and France (two cases). Here, we report the isolation of
      BBLV in a Natterer's bat (Myotis nattereri) in Poland. The bat brain tested
      positive for rabies using classical diagnostics tests (FAT and RTCIT) and then
      subsequently confirmed by molecular techniques. Viral RNA was found in all
      peripheral organs tested, and the highest viral loads were detected in brain, the
      salivary gland and bladder. Phylogenetic analysis performed on complete viral
      genome sequences revealed the closest homology to representatives of BBLV lineage
      B, isolated previously in southern Germany. This case provides further evidence
      that BBLV is widespread in Europe.

PMID- 30198170
TI  - Tuning the Anomeric Effect in Sulfamide with Superacids.
AB  - This study shows that the anomeric effect (negative hyperconjugation) that arises
      in sulfamide, as a result of the relatively short S-N bonds, can be tuned by the
      utilization of superacidic media. Sulfamide was reacted in binary superacidic
      systems XF/MF5 (M=As, Sb; X=H, D) and HF/BF3 . The colorless salts formed, [X2
      NSO2 NX3 ]+ [MF6 ]- and [H2 NSO2 NH3 ]+ [BF4 ]- were characterized by low
      temperature vibrational spectroscopy. In the case of [H2 NSO2 NH3 ]+ [BF4 ]- , a
      single crystal X-ray diffraction study was performed. The salt crystallizes in
      the monoclinic space group P21 /c with four formula units per unit cell. An
      exclusive N,N'-diprotonation was observed in the superacidic system HF/SbF5 when
      using several equivalents of the Lewis acid. Low-temperature vibrational spectra
      as well as a single-crystal X-ray structure of [H3 NSO2 NH3 ]2+ 2 [SbF6 ]- ?2 HF
      are reported. The salt crystallizes in the orthorhombic space group Pna21 with
      four formula units per unit cell. Upon mono- or diprotonation of sulfamide,
      remarkable structural changes of the sulfur-nitrogen bond lengths were observed.
      Herein, these changes are discussed together with quantum chemical calculations.

PMID- 30198171
TI  - First record of Pomacanthus maculosus (Perciformes, Pomacanthidae) in the south
      western Atlantic Ocean.
AB  - A single Pomacanthus maculosus was filmed during a scuba diving survey on a rocky
      reef from southern Brazil. The body shape and coloration pattern confirmed the
      species identification. The biological and ecological characteristics of P.
      maculosus and the long distance of Brazil from its original distribution strongly
      suggest of an anthropogenic pathway of dispersion.

PMID- 30198172
TI  - Adaptive growth changes in the liver remnant are affected by the size of
      hepatectomy in rats.
AB  - In this study we investigated the dynamics of hepatocyte hyperplasia and
      hypertrophy in rats subjected to increasing sizes of partial hepatectomy (PH). A
      total of 104 rats were randomized according to the size of PH. On postoperative
      days (PODs) 1, 3 and 5, blood was drawn and the remnant liver removed for
      stereological analysis. Liver parameters and regeneration rate were significantly
      affected by size of PH. On POD 1, hepatocyte volumes had increased significantly
      in all PH groups. On POD 3, all groups showed hepatocyte volumes approximating
      baseline. On POD 5, hepatocyte volumes were significantly lower in PH (90) than
      in baseline, sham and PH (30) rats. Increasing hepatocyte proliferation was not
      observed following PH (30). Following PH (70), cell proliferation was
      significantly elevated on PODs 1 and 3, and following PH (90) on PODs 3 and 5. In
      conclusion, general hypertrophy of hepatocytes after different size of PH was
      followed by hepatocyte proliferation only in the liver remnant of PH (70) and PH
      (90).

PMID- 30198173
TI  - Conflict management among health professionals in hospitals of Cyprus.
AB  - AIM: To record the types of conflict management that health professionals in
      Cyprus hospitals encounter in their daily work and to explore the conflicts,
      their parameters and causes, and the role ambiguity faced by the hospital
      employees. MATERIAL AND METHODS: This is a descriptive study in which data were
      collected with an anonymous self-referral questionnaire. The study population
      consisted of 300 health professionals from six different hospitals in Cyprus.
      Data are presented with averages and standard deviations. RESULTS: The health
      professionals identified the following causes of conflicts in the workplace in
      descending order: heavy workload, low pay, and varying instructions from
      different leaders. To deal with the conflict, 73.2% of the participants reported
      using avoidance, 54.2% engaged in negotiation for mutual benefit, and 40.5% cited
      compromise as a method. CONCLUSIONS: Identifying the way in which conflicts are
      managed contributes to the smooth functioning of organisations, and it improves
      the effectiveness of the services provided. IMPLICATIONS FOR NURSING MANAGEMENT:
      It is generally known that the high levels of conflict in hospitals are
      associated with increased mistakes and low employee satisfaction and performance
      levels. Managers deal with conflict-management issues within organisations on a
      daily basis. It is therefore essential to comprehend the reasons behind conflicts
      and provide suitable training for the development of communication skills and
      conflict-management strategies.

PMID- 30198174
TI  - Quantitative proteomic analysis of mitochondrial proteins differentially
      expressed between small cell lung cancer cells and normal human bronchial
      epithelial cells.
AB  - BACKGROUND: Small cell lung cancer (SCLC) is highly aggressive and is associated
      with a dismal prognosis. However, there are no clinically recognized biomarkers
      for early diagnosis. In this study, we used quantitative proteomics to build
      differential mitochondrial protein profiles that may be used for early diagnosis
      and investigated the pathogenesis of lung cancer. METHODS: We cultured SCLC cells
      (NCI-H446) and normal human bronchial epithelial cells (16-HBE); mitochondria
      were extracted and purified using differential and Percoll density gradient
      centrifugation. Subsequently, we used Western blot analysis to validate
      mitochondrial purity and labeled proteins/peptides from NCI-H446 and 16-HBE cells
      using relative and absolute quantification of ectopic tags. We then analyzed
      mixed samples and identified proteins using two-dimensional liquid chromatography
      tandem mass spectrometry. Additionally, we performed subsequent bioinformatic
      proteome analyses using the programs ExPASy, GOA, and STRING. Finally, the
      relationship between ornithine aminotransferase expression and
      clinicopathological features in lung cancer patients was evaluated using
      immunohistochemistry. RESULTS: One hundred and fifty-three mitochondrial proteins
      were differentially expressed between 16-HBE and NCI-H446 cells. The expression
      of 30 proteins between 16-HBE and NCI-H446 cells increased more than 1.3-fold.
      The upregulation of ornithine aminotransferase was associated with pathological
      grade and clinical tumor node metastasis stage. CONCLUSION: Our experiment
      represented a promising method for building differential mitochondrial protein
      profiles between NCI-H446 and 16-HBE cells. Such analysis may also help to
      identify novel biomarkers of lung cancer.

PMID- 30198175
TI  - Predictive risk factors for complicated pneumonia in Malaysian children.
AB  - AIM: To investigate baseline characteristics associated with complicated
      community-acquired pneumonia (CAPc) in Malaysian children. CAPc, such as pleural
      effusion and/or empyema, is on the rise, especially in Southeast Asian children,
      and the reasons for this are unknown. METHODS: A retrospective study was
      conducted on all children aged 2-16 years who were admitted to the University
      Malaya Medical Centre with community-acquired pneumonia between 2012 and 2014.
      RESULTS: In this study, of the 343 children, 58 (17%) developed CAPc. Chinese
      ethnicity (P < 0.001), reduced breastfeeding duration (P = 0.003), not receiving
      outpatient antibiotic (P < 0.001) and exposure to parental smoking (P < 0.001)
      were identified as risk factors for CAPc. Markedly increased respiratory rate (P
      = 0.021) and thrombocytosis (P < 0.001) were noted as the clinical parameters for
      CAPc. CONCLUSION: This study identifies some modifiable risk to reduce the burden
      of pneumonia complications.

PMID- 30198177
TI  - Masking the Peroxidase-Like Activity of the Molybdenum Disulfide Nanozyme Enables
      Label-Free Lipase Detection.
AB  - Two-dimensional MoS2 nanoparticles (2D-nps) exhibit artificial enzyme properties
      that can be regulated at bio-nanointerfaces. We discovered that protein lipase is
      able to tune the peroxidase-like activity of MoS2 2D-nps, offering low-nanomolar,
      label-free detection and identification in samples with unknown identity. The
      inhibition of the peroxidase-like activity of the MoS2 2D-nps was demonstrated to
      be concentration dependent, and as low as 5 nm lipase was detected with this
      approach. The results were compared with those obtained with several other
      proteins that did not display any significant interference with the nanozyme
      behavior of the MoS2 2D-nps. This unique response of lipase was characterized and
      exploited for the successful identification of lipase in six unknown samples by
      using qualitative visual inspection and a quantitative statistical analysis
      method. The developed methodology in this approach is noteworthy for many
      aspects; MoS2 2D-nps are neither labeled with a signaling moiety nor modified
      with any ligands for signal readout. Only the intrinsic nanozyme activity of the
      MoS2 2D-nps is exploited for this detection approach. No analytical equipment is
      necessary for the visual detection of lipase. The synthesis of the water-soluble
      MoS2 2D-nps is low costing and can be performed in bulk scale. Exploring the
      properties of 2D-nps and their interactions with biological materials reveals
      highly interesting yet instrumental features that offer the development of novel
      bioanalytical approaches.

PMID- 30198178
TI  - Environmental microbiology and metagenomics: the Brave New World is here, what's
      next?

PMID- 30198176
TI  - Role of age, Rho-kinase 2 expression, and G protein-mediated signaling in the
      myogenic response in mouse small mesenteric arteries.
AB  - : The myogenic response (MR) and myogenic tone (MT) in resistance vessels is
      crucial for maintaining peripheral vascular resistance and blood flow
      autoregulation. Development of MT involves G protein-coupled receptors, and may
      be affected by aging. AIMS: (1) to estimate the mesenteric blood flow in
      myogenically active small mesenteric arteries; (2) to investigate the signaling
      from Galphaq/11 and/or Galpha12 activation to MT development; (3) to investigate
      the role of Rho-kinase 2 and aging on MT in mesenteric resistance arteries.
      METHODS: we used pressure myography, quantitative real-time PCR, and
      immunolocalization to study small (<200 MUm) mesenteric arteries (SMA) from
      young, mature adult, and middle aged mice. RESULTS: Poiseuille flow calculations
      indicated autoregulation of blood flow at 60-120 mm Hg arterial pressure.
      Galphaq/11 and Galpha12 were abundantly expressed at the mRNA and protein levels
      in SMA. The Galphaq/11 inhibitor YM-254890 suppressed MT development, and the
      Phosholipase C inhibitors U73122 and ET-18-OCH3 robustly inhibited it. We found
      an age-dependent increase in ROCK2 mRNA expression, and in basal MT. The specific
      ROCK2 inhibitor KD025 robustly inhibited MT in SMAs in all mice with an age
      dependent variation in KD025 sensitivity. The inhibitory effect of KD025 was not
      prevented by the L-type Ca2+ channel activator BayK 8644. KD025 reversibly
      inhibited MT and endothelin-1 vasoconstriction in small pial arteries from
      Gottingen minipigs. CONCLUSIONS: MT development in SMAs occurs through a
      Galphaq/11 /PLC/Ca2+ -dependent pathway, and is maintained via ROCK2-mediated
      Ca2+ sensitization. Increased MT at mature adulthood can be explained by
      increased ROCK2 expression/activity.

PMID- 30198179
TI  - The Torg ratio of C3-C7 in African-Americans and European-Americans: A skeletal
      study.
AB  - INTRODUCTION: The ratio between the sagittal diameter of the spinal canal and the
      sagittal diameter of the vertebral body, known as the "Torg ratio", is often used
      to test for spinal canal narrowing. Here we investigate this ratio in a large
      population, consisting of two ethnicities, both sexes and three age groups.
      MATERIALS AND METHODS: Measurements were taken on the dry cervical verterbrae (C3
      C7) of 277 individuals using a digital apparatus allowing for the recording of 3D
      coordinates of a set of landmarks on the vertebral body. Vertebral body and
      vertebral foramen lengths were compared across the different sub-groups. RESULTS:
      Vertebral body and vertebral foramen lengths differ significantly between males
      and females and between African-Americans and European-Americans. With age, the
      vertebral body length increases while the foramen length does not undergo
      significant changes. These anatomical differences are reflected in differences in
      the Torg ratio calculated for the different sub-groups. CONCLUSIONS: Our findings
      suggest that a hard cut-off on the Torg ratio used to define a pathological
      narrowing of the cervical spine should be adapted to the population the patients
      come from. This article is protected by copyright. All rights reserved.

PMID- 30198180
TI  - Efficient Self-Driven Photodetectors Featuring a Mixed-Dimensional van der Waals
      Heterojunction Formed from a CdS Nanowire and a MoTe2 Flake.
AB  - Heterojunctions formed from low-dimensional materials can result in photovoltaic
      and photodetection devices displaying exceptional physical properties and
      excellent performance. Herein, a mixed-dimensional van der Waals (vdW)
      heterojunction comprising a 1D n-type Ga-doped CdS nanowire and a 2D p-type MoTe2
      flake is demonstrated; the corresponding photovoltaic device exhibits an
      outstanding conversion efficiency of 15.01% under illumination with white light
      at 650 uW cm-2 . A potential difference of 80 meV measured, using Kelvin probe
      force microscopy, at the CdS-MoTe2 interface confirms the separation and
      accumulation of photoexcited carriers upon illumination. Moreover, the
      photodetection characteristics of the vdW heterojunction device at zero bias
      reveal a rapid response time (<50 ms) and a photoresponsivity that are linearly
      proportional to the power density of the light. Interestingly, the response of
      the vdW heterojunction device is negligible when illuminated at 580 nm; this
      exceptional behavior is presumably due to the rapid rate of recombination of the
      photoexcited carriers of MoTe2 . Such mixed-dimensional vdW heterojunctions
      appear to be novel design elements for efficient photovoltaic and self-driven
      photodetection devices.

PMID- 30198181
TI  - Transanal completion proctectomy with close rectal dissection and ileal pouch
      anal anastomosis for ulcerative colitis.
AB  - INTRODUCTION: Laparoscopic dissection in the pelvis is still a challenge. A
      transanal approach to rectal dissection allows better visualization during the
      dissection of the rectum and the creation of an anastomosis. Although initially
      used for patients with rectal cancer, the transanal approach may also have
      benefits in the surgical treatment of ulcerative colitis (UC). The aim of this
      study was to describe our initial experience with transanal completion
      proctectomy and ileal pouch-anal anastomosis for UC. METHODS: This study included
      all consecutive patients who underwent transanal completion proctectomy and ileal
      pouch-anal anastomosis for UC between September 2017 and February 2018. RESULTS:
      Eleven patients were included in the study; they had a median age of 30 years
      (range, 13-51 years). The median operative time was 285 min (range, 190-375 min).
      There were no intraoperative complications or conversions to open surgery.
      Postoperative complications occurred in only one patient (anastomotic leak), and
      the median length of hospital stay was 7 days (range, 5-37 days). CONCLUSION: Our
      initial experience with transanal completion proctectomy and ileal pouch-anal
      anastomosis shows promising results, demonstrating the feasibility of the
      transanal approach in patients with UC.

PMID- 30198182
TI  - Development and testing of a patient-derived questionnaire for treatment of
      neovascular age-related macular degeneration: dimensions of importance in
      treatment of neovascular age-related macular degeneration.
AB  - PURPOSE: Studies reporting on patient perspectives during treatment of
      neovascular age-related macular degeneration (nAMD) are limited. Thus, the aim of
      this study was to develop and test psychometric performance of a patient-derived
      questionnaire to capture important experiences during intravitreal treatment.
      METHODS: Patients (n = 44) with at least 3-month experience of intravitreal
      injection treatment for nAMD identified the dimensions of priority and also
      performed a weighting procedure to develop a score for comparison. The
      questionnaire comprised two versions: one focusing on the relative importance' of
      the dimensions and one on the experience of the 'management' during treatment.
      The questionnaire was then tested for psychometric performance in a longitudinal
      design in newly diagnosed patients at baseline (n = 197), after three (n = 184)
      and six (n = 150) months of treatment. RESULTS: Of the 15 included dimensions,
      the following were most frequently reported: 'receive treatment to preserve
      vision', 'information', 'waiting time', 'trust' and 'accommodating staff. The
      psychometric testing showed moderate reliability (intraclass correlation
      coefficient: 0.65-0.67) for the two versions and high level of face validity
      (8.3). The dimensions, 'preserving vision', 'early access to treatment', 'pain
      relief', 'information about the treatment/diagnosis' and 'visual aids' were
      consistently reported higher in 'importance' than in 'management', at both 3 and
      6 months, indicating a potential for improvement in clinical practice for these
      dimensions. CONCLUSION: This study provides a brief patient-derived
      questionnaire, expressed with a score with good psychometric performance that can
      be used for monitoring during intravitreal injection treatment of nAMD patients.

PMID- 30198183
TI  - Monthly spending dynamics of the elderly following a health shock: Evidence from
      Singapore.
AB  - We use novel longitudinal data from 19 monthly waves of the Singapore Life Panel
      to examine the short-term dynamics of the effects health shocks have on household
      health and nonhealth spending and income by the elderly. The health shocks we
      study are the occurrence of new major conditions such as cancer, heart problems,
      and minor conditions (e.g., diabetes and hypertension). Our empirical strategy is
      based on an event study approach that exploits unanticipated changes in health
      status through the diagnosis of new health conditions. We find that major shocks
      have large and persistent effects whereas minor shocks have small and mainly
      contemporaneous effects. We find that household income reduces following a major
      shock for males but not females. Major health shocks lead to a decrease in
      households' nonhealth expenditures that is particularly pronounced for cancer and
      stroke sufferers, driven largely by reductions in leisure spending. The financial
      impact of major shocks on medical saving account balances occurs to those without
      private health insurance, whereas the impact is on cash balances for privately
      insured individuals.

PMID- 30198184
TI  - Interference between arsenic-induced toxicity and hypoxia.
AB  - Plants often face combinatorial stresses in their natural environment. Here,
      arsenic (As) toxicity was combined with hypoxia (Hpx) in the roots of Arabidopsis
      thaliana as it often occurs in nature. Arsenic inhibited growth of both roots and
      leaves, whereas root growth almost entirely ceased in Hpx. Growth efficiently
      resumed, and Hpx marker transcripts decreased upon reaeration. Compromised
      recovery from HpxAs treatment following reaeration indicated some persistent
      effects of combined stresses despite lower As accumulation. Root glutathione
      redox potential turned more oxidized in Hpx and most strongly in HpxAs. The more
      oxidizing root cell redox potential and the lowered glutathione amounts may be
      conducive to the growth arrest of plants exposed to HpxAs. The stresses elicited
      changes in elemental and transcriptomic composition. Thus, calcium, magnesium,
      and phosphorous amounts decreased in rosettes, but the strongest decline was seen
      for potassium. The reorganized potassium-related transcriptome supports the
      conclusion that disturbed potassium homeostasis contributes to the growth
      phenotype. In a converse manner, photosynthesis-related parameters were hardly
      affected, whereas accumulated carbohydrates under all stresses and anthocyanins
      under Hpx exclude carbohydrate limitation. The study demonstrates the existence
      of both synergistic since mutually aggravating effects and antagonistic effects
      of single and combined stresses.

PMID- 30198187
TI  - Mirroring the multifaceted role of RNA and its partners in gene expression.

PMID- 30198185
TI  - Selection of Higher Risk Pregnancies into Veterans Health Administration
      Programs: Discoveries from Linked Department of Veterans Affairs and California
      Birth Data.
AB  - OBJECTIVE: To describe variation in payer and outcomes in Veterans' births.
      DATA/SETTING: Secondary data analyses of deliveries in California, 2000-2012.
      STUDY DESIGN: We performed a retrospective, population-based study of all live
      births to Veterans (confirmed via U.S. Department of Veterans Affairs (VA)
      enrollment records), to identify payer and variations in outcomes among: (1)
      Veterans using VA coverage and (2) Veteran vs. all other births. We calculated
      odds ratios (aOR) adjusted for age, race, ethnicity, education, and obstetric
      demographics. METHODS: We anonymously linked VA administrative data for all
      female VA enrollees with California birth records. PRINCIPAL FINDINGS: From 2000
      to 2012, we identified 17,495 births to Veterans. VA covered 8.6 percent (1,508),
      Medicaid 17.3 percent, and Private insurance 47.6 percent. Veterans who relied on
      VA health coverage had more preeclampsia (aOR 1.4, CI 1.0-1.8) and more cesarean
      births (aOR 1.2, CI 1.0-1.3), and, despite similar prematurity, trended toward
      more neonatal intensive care (NICU) admissions (aOR 1.2, CI 1.0-1.4) compared to
      Veterans using other (non-Medicaid) coverage. Overall, Veterans' birth outcomes
      (all-payer) mirrored California's birth outcomes, with the exception of excess
      NICU care (aOR 1.15, CI 1.1-1.2). CONCLUSIONS: VA covers a higher risk fraction
      of Veterans' births, justifying maternal care coordination and attention to the
      maternal-fetal impacts of Veterans' comorbidities.

PMID- 30198186
TI  - Anaphylaxis caused by alginate dressing.

PMID- 30198188
TI  - Asymptomatic hyperkeratotic linear plugs on the right hand of a young woman.

PMID- 30198189
TI  - Treatment planning based on water density image generated using dual-energy
      computed tomography for pancreatic cancer with contrast-enhancing agent: Phantom
      and clinical study.
AB  - PURPOSE: A contrast-enhancing agent is imperative for the accurate target
      delineation of pancreatic tumors. This study demonstrates the potential use of
      treatment planning for patients with pancreatic tumors based on the water density
      image (WDI) generated by dual-energy computed tomography (DECT). METHODS: Tissue
      characterization and multi-energy phantom scanning were performed through DECT
      and the physical characteristics of the WDI and a virtual monochromatic image
      (VMI) were assessed. The measured and the corresponding theoretical electron
      density relative to water (RED) and mass density (MD) were compared. Treatment
      plans based on the WDI (TPWDI ) and VMI (TPVMI ) were compared for 22 pancreatic
      cancer patients who underwent contrast-enhanced DECT scan. RESULTS: The total
      absolute difference in the HU value between the conventional 120 kVp images and
      the VMI was the smallest at the energy level of 77 keV (3.3 HU), and the VMI at
      77 keV was used for subsequent analysis. The difference between the measured and
      theoretical values of RED and MD for iodine using the VMI (>15%) was larger than
      that using WDI (<4%). In clinical cases, the maximum difference in the dosimetric
      parameters between TPWDI and TPWDI for the planning target volume was 3.0% when
      the doses were calculated using AXB, and for the duodenum, it was 1.7%.
      CONCLUSIONS: The WDI estimated the RED and MD accurately and could form the basis
      for a new treatment planning approach for pancreatic cancer using contrast
      enhancing agent.

PMID- 30198190
TI  - Nephrogenic systemic fibrosis: in a child with primary hyperoxaluria.

PMID- 30198191
TI  - Environment and past land use together predict functional diversity in a
      temperate forest.
AB  - Environment and human land use both shape forest composition. Abiotic conditions
      sift tree species from a regional pool via functional traits that influence
      species' suitability to the local environment. In addition, human land use can
      modify species distributions and change functional diversity of forests. However,
      it is unclear how environment and land use simultaneously shape functional
      diversity of tree communities. Land-use legacies are especially prominent in
      temperate forest landscapes that have been extensively modified by humans in the
      last few centuries. Across a 900-ha temperate deciduous forest in the
      northeastern United States, comprising a mosaic of different-aged stands due to
      past human land use, we used four key functional traits-maximum height, rooting
      depth, wood density, and seed mass-to examine how multiple environmental and land
      use variables influenced species distributions and functional diversity. We
      sampled ~40,000 trees >8 cm DBH within 485 plots totaling 137 ha. Species within
      plots were more functionally similar than expected by chance when we estimated
      functional diversity using all traits together (multi-trait), and to a lesser
      degree, with each trait separately. Multi-trait functional diversity was most
      strongly correlated with distance from the perennial stream, elevation, slope,
      and forest age. Environmental and land-use predictors varied in their correlation
      with functional diversities of the four individual traits. Landscape-wide change
      in abundances of individual species also correlated with both environment and
      land-use variables, but magnitudes of trait-environment interactions were
      generally stronger than trait interactions with land use. These findings can be
      applied for restoration and assisted regeneration of human-modified temperate
      forests by using traits to predict which tree species would establish well in
      relation to land-use history, topography, and soil conditions.

PMID- 30198192
TI  - Positive reactions to gold sodium thiosulfate in patch test panels (TRUE Test) in
      Japan: A multicentre study.
AB  - BACKGROUND: The proportion of positive test results with gold sodium thiosulfate
      included in a patch test panel (P-GST) had been found to be greater than that
      with gold sodium thiosulfate 0.5% pet. by allergEAZE (A-GST). OBJECTIVES: To
      compare positive reactions to P-GST and A-GST, and to evaluate late reactions
      after the day (D) 7 reading. METHODS: A retrospective analysis was performed of
      588 patients at participating departments (119 males; 469 females) who were patch
      tested with P-GST and A-GST in May 2015 to March 2016. RESULTS: Positive test
      reactions to P-GST and A-GST were observed in 15% and 6% of patients,
      respectively. Three patients reported a positive reaction occurring after the D7
      reading. CONCLUSIONS: Gold sodium thiosulfate often gives a positive reaction
      after 2 to 3 weeks, and, in such cases, the positive reaction may be sustained,
      so it is recommended to assess the reaction for up to 1 month after application.

PMID- 30198193
TI  - Day light photodynamic therapy with BF-200 ALA: A case series.

PMID- 30198194
TI  - Studying the fragmentation mechanism of selected components present in crude oil
      by collision-induced dissociation mass spectrometry.
AB  - RATIONALE: Structural characterization of individual compounds in very complex
      mixtures is difficult to achieve. One important step in structural elucidation is
      understanding the mass spectrometric fragmentation mechanisms of the compounds
      present in such mixtures. Here, different individual compounds presumed to be
      present in a complex crude oil mixture have been synthesized and structurally
      characterized by tandem mass spectrometry (MS/MS) studies. METHODS: Model
      compounds with different aromatic cores and various substitutents were
      synthesized. Major effort has been put into producing isomerically pure compounds
      to better understand the fragmentation pattern. Each synthesized compound has
      been subjected to MSn studies using either a triple quadrupole or a linear ion
      trap mass spectrometer with electrospray or atmospheric pressure photoionization.
      The results are used to analyze individual compounds from a complex vacuum gas
      oil (VGO). RESULTS: The synthesized compounds and a chromatographically
      simplified vacuum gas oil were used for structural analysis. The major
      fragmentation mechanism is the benzylic cleavage of the aliphatic side chain.
      Each side chain can be separately removed from the aromatic core by using MSn
      methods. At the end of a series of fragmentations, the base aromatic core
      structure remains and can be chararcterized. CONCLUSIONS: By defining the
      fragmentation mechanism in complex oil samples it was possible to structurally
      characterize individual compounds present in a chromatographically simplified
      VGO. The compounds consist of an aromatic core with aliphatic side chains.
      Cleavage of all side chains can be achieved by MSn measurements, allowing
      characterization of the remaining core structure.

PMID- 30198195
TI  - Estimation of adjusted expected excess length-of-stay associated with ventilation
      acquired pneumonia in intensive care: A multistate approach accounting for time
      dependent mechanical ventilation.
AB  - The expected excess length-of-stay is an established concept to assess the health
      and economic impact of nosocomial, that is, hospital-acquired infections such as
      ventilation-acquired pneumonia in intensive care. Estimation must account for the
      timing of infection as in a multistate perspective, because common retrospective
      comparisons yield inflated estimates due to time-dependent bias. Since occurrence
      of ventilation-acquired pneumonia is closely linked to ventilation status, we
      suggest a multistate model incorporating time-dependent mechanical ventilation as
      additional states. The appeal is that the expected excess length-of-stay
      decomposes into extra days spent under ventilation and not under ventilation.
      This is not only highly relevant from a patient's perspective regarding quality
      of life, but also from an economic point of view, because ventilation is a major
      cost driver. The challenge is that estimation involves complex functionals of the
      matrix of transition probabilities, which in turn are based on the transition
      hazards. To address heterogeneity between patients, which is a common phenomenon
      in observational hospital epidemiology, we apply pseudovalue regression to adjust
      the ventilation-specific quantities for baseline confounding. The performance of
      our proposal is assessed by simulation and the methods are illustrated on data
      provided by 12 French intensive care units. Preliminary results indicate that the
      expected excess length-of-stay associated with ventilation-acquired pneumonia is
      mainly triggered by extra days spent under mechanical ventilation, and that the
      excess is most pronounced for intensive care patients with fewer comorbidities at
      baseline. We also find that such a decomposition is challenging for early times.
      Example code is provided.

PMID- 30198196
TI  - A prospective comparative analysis of robot-assisted vs open simple prostatectomy
      for benign prostatic hyperplasia.
AB  - OBJECTIVE: To report the first prospective comparative analysis of robot-assisted
      (RASP) vs open simple prostatectomy (OSP) for large prostate glands. MATERIALS
      AND METHODS: We prospectively analysed 41 patients who underwent surgery for
      benign prostatic hyperplasia between 2014 and 2017 at one of two university
      institutions. Patients were grouped according to the procedure (OSP or RASP) and
      matched in terms of age, prostate volume, body mass index and prostate-specific
      antigen level. The two groups were followed prospectively for 3 months, and their
      postoperative and functional outcomes were compared. RESULTS: Six patients (40%)
      in the OSP and seven patients (27%) in the RASP arm of the study had preoperative
      urethral catheters as a result of relapsed urinary retention. The amount of blood
      loss during surgery was significantly lower in the RASP arm (539  vs 274 mL), but
      the operating time was significantly longer (134 vs 88 min). One patient in the
      RASP group experienced a Clavien-Dindo grade II complication, whereas in the OSP
      group, four patients experienced serious complications (27%); one patient had a
      bladder rupture (Grade III), one patient developed deep venous thrombosis (Grade
      II), and two patients required blood transfusions (one unit each; Grade II). Two
      patients (one from each group) experienced urinary retention after catheter
      removal that required a urethral catheter replacement. In the follow-up period,
      there were significant and similar improvements in International Prostate Symptom
      Scores, uroflowmetry results and post-void residual urine volume in both groups.
      CONCLUSION: The results showed that RASP provided similar functional outcomes to
      those of OSP, whilst maintaining a good (or even better) safety profile. Our
      results suggest that RASP is a viable, efficient and potentially superior
      alternative to the open procedure.

PMID- 30198197
TI  - Epidemic cycles and environmental pressure in colonial Quebec.
AB  - OBJECTIVES: Research on historical populations in Europe finds that infectious
      disease epidemics appear to induce predictable cycles in age-specific mortality.
      We know little, however, about whether such cycles also occurred in less dense
      founder populations of North America. We used high-quality data on the Quebecois
      population from 1680 to 1798 to examine the extent to which age-specific
      mortality showed predictable epidemic cycles. We further examined whether
      environmental pressures-temperature, lack of precipitation, or crop failure-may
      have set the stage for the emergence of epidemics. METHODS: We applied
      autoregressive, integrated, moving average time series methods to annual counts
      of period mortality for the following age groups: < 1 year, 1 to < 5 years, 5 to
      < 15 years, 15 to < 50 years, and 50 years and above. These methods controlled
      for other patterns (e.g., trend) before empirically identifying cycles. RESULTS:
      Results indicate a strong seven-year cycle in mortality among infants and
      children under seven years of age. Warm temperatures (across Quebec overall) and
      relatively dry years (in Eastern Quebec) also predicted an increased risk of
      mortality in infancy and childhood, although these environmental variables appear
      to act independently of the epidemic cycle pattern. DISCUSSION: Findings indicate
      a strong seven-year epidemic cycle in historical Quebec which afflicted naive
      birth cohorts not previously exposed to the prior epidemic. We contend that
      smallpox epidemics likely contributed to this cycle. The seven-year cycle
      occurred only in the latter half of the test period (post 1740) with increasing
      size of the colony and population concentration in urban areas.

PMID- 30198198
TI  - An exploratory experimental study examining the short-term effects of a public
      service announcement on parents' perceptions of the descriptive norm for
      children's outdoor play: A cautionary tale.
AB  - ISSUE ADDRESSED: Public service announcements (PSA) targeting physical activity
      are not always effective at enacting behaviour change. One factor that may impact
      message effectiveness is whether the message matches its intent (ie, what norm is
      being portrayed and received). The current study explored the effects of two PSAs
      on parents' perceptions of outdoor play. METHODS: Parents (N = 333) completed a
      pre/postexperimental online survey to examine the acute impact of a PSA on their
      perception of how often children play outdoors (ie, descriptive norms).
      Participants provided their descriptive norm perceptions and then were randomised
      to view one of two PSAs: (a) the Mr. Lonely PSA, which portrayed outdoor activity
      as not normative, and (b) a control message, which portrayed outdoor activity as
      the norm (VERB PSA). After viewing their PSA, descriptive norm perceptions were
      reported again. RESULTS: A two-way mixed ANOVA indicated that participants who
      viewed the Mr. Lonely PSA (where outdoor play was not normative) perceived that
      children and youth played outdoors less frequently immediately after watching the
      PSA compared to before viewing it (P < 0.05). No significant change occurred in
      the control condition. CONCLUSIONS: PSAs can alter individuals' perceptions of
      whether they perceive outdoor play as normative among children and youth. SO
      WHAT?: As individuals align their behaviour with what is typical, PSA developers
      should be wary of what message is being conveyed. In terms of activity,
      portraying that outdoor play is not normative may not have the intended outcome.

PMID- 30198199
TI  - Ultrasound-guided femoral nerve blocks are not superior to ultrasound-guided
      fascia iliaca blocks for fractured neck of femur.
AB  - OBJECTIVE: To determine if an ultrasound-guided femoral nerve block (FNB) is
      superior to an ultrasound-guided fascia iliaca compartment block (FICB) in
      providing pain relief to patients with a neck of femur or proximal femoral
      fracture. METHODS: A double-blind randomised controlled trial was conducted. All
      participants received two blocks, one active and one placebo. An active FICB was
      administered to 52 participants and 48 participants received an active FNB.
      RESULTS: Analysis was completed on data collected from 100 participants. Most
      patients were elderly and the majority were female. Both FICB and FNB achieved
      clinically significant mean reductions in pain scores (2.62 for FICB and 2.3 for
      FNB). There was no significant difference in reduction in pain scores between the
      two cohorts, P = 0.408. CONCLUSIONS: Ultrasound-guided FNB is not superior to
      ultrasound-guided FICB, with both facilitating an equivalent analgesia effect in
      patients with a neck of femur or proximal femur fracture.

PMID- 30198200
TI  - Pectoralis major radiation recall.
AB  - Radiation recall is an uncommon phenomenon describing an acute localised
      inflammatory toxicity affecting tissue previously exposed to radiotherapy. It is
      precipitated by administration of certain medications, including chemotherapy. We
      describe a case involving a 50-year-old Aboriginal male smoker from a remote
      community in Northern Australia who underwent treatment for stage IV non-small
      cell lung cancer with localised radiotherapy to the primary right upper lung lobe
      tumour. This was followed by a course of gemcitabine, which was ceased
      prematurely after four cycles when he presented with radiation recall to his
      right pectoralis major. Our case description is complemented with a brief review
      of current literature regarding our case and gemcitabine-related radiation
      recall. This was in the context of concurrent musculoskeletal strain, an as-yet
      unreported association with radiation recall. His condition settled with steroid
      administration and discontinuation of gemcitabine.

PMID- 30198201
TI  - Validation of the Prodromal Questionnaire-Brief in a representative sample of
      adolescents: Internal structure, norms, reliability, and links with
      psychopathology.
AB  - OBJECTIVES: The main purpose of the present study was twofold: to validate the
      Prodromal Questionnaire-Brief (PQ-B) in a community-derived sample of adolescents
      and to examine the links between psychotic-like experiences and emotional and
      behavioral problems, prosocial behavior, suicidal ideation, and bipolar-like
      experiences. METHOD: One thousand five hundred eighty-eight students selected by
      random sampling participated in a cross-sectional survey. The PQ-B, Paykel
      Suicide Scale, Strengths and Difficulties Questionnaire, Mood Disorder
      Questionnaire, Penn Matrix Reasoning Test, Family Affluence Scale-II, and Oviedo
      Infrequency Scale were used. RESULTS: The unidimensional factorial structure of
      the PQ-B items showed adequate goodness of fit index. This model also showed
      configural and strong invariance across gender. The internal consistency of the
      PQ-B total frequency score was 0.92. A high degree of overlap was found between
      psychotic-like experiences and emotional and behavioral problems, suicidal
      ideation, and bipolar-like experiences. CONCLUSION: The PQ-B is a brief, easy,
      and reliable tool for screening psychotic-like experiences in adolescents from
      the general population. The assessment of risk for psychosis and its relationship
      with other psychopathological risk factors in a close-in strategy or two-stage
      process model may help us to enhance the early identification for youths at
      heightened risk for serious mental disorders.

PMID- 30198202
TI  - Facial nevus depigmentosus getting remarkable repigmentation by treatment with a
      308-nm excimer laser: A case report.
AB  - Nevus depigmentosus (ND) is a rare, congenital, nonprogressive depigmented lesion
      with irregular outline. To date, the few therapeutic approaches that have been
      developed to treat ND have yielded unsatisfactory results. We reported on a 6
      month-old girl who presented with a ND on the right side of her face for 5
      months. Treatment with a 308-nm excimer laser was started once a week at 300
      mJ/cm2 and then was increased by 50-100 mJ/cm2 in each subsequent session until
      post-treatment erythema occurred. After 10 treatments, repigmentation in the
      lesion was evident and remained stable 1 month later at follow up. This case
      supports that the 308-nm excimer laser may be a good choice for the treatment of
      ND.

PMID- 30198203
TI  - Comments on "Unambiguous identification and characterization of a long-term human
      metabolite of dehydrochloromethyltestosterone".

PMID- 30198204
TI  - Efficacy of adjunctive low-level laser therapy in the treatment of aggressive
      periodontitis: A systematic review.
AB  - The aim of the present study was to systematically review the efficacy of low
      level laser therapy (LLLT) as an adjunct to scaling and root planing (SRP) vs SRP
      alone in the treatment of aggressive periodontitis (AgP). The addressed PICO
      (Population, Interventions, Comparisons and Outcomes) question was: Is LLLT as an
      adjunct to SRP effective in the treatment of AgP? Electronic databases, including
      MEDLINE via PubMed, Cochrane Central Register of Controlled Trials and Cochrane
      Oral Health Group Trials, and EMBASE, were searched until March 2018. Four
      clinical studies were included. Three studies showed significant improvement in
      periodontal outcomes among LLLT group compared to SRP alone, whereas only one
      study showed comparable periodontal outcomes between the adjunctive LLLT and SRP
      groups at follow up. The overall mean difference for clinical attachment level
      gain (weighted mean difference [WMD] = -1.69, 95% confidence interval [CI] = 
      3.46 to 0.07, P < 0.061) was not significant. However, significant difference for
      probing depth reduction (WMD = -0.95, 95% CI = -1.66 to 0.23, P = 0.009) was
      noticed between groups at follow up. Whether LLLT as an adjunct to SRP is more
      effective than SRP alone in the treatment of AgP remains debatable. Further
      randomized, clinical trials are required with long follow-up periods and standard
      laser parameters to reach a strong conclusion.

PMID- 30198205
TI  - Age, growth and reproductive biology of threatened westslope cutthroat trout
      Oncorhynchus clarkii lewisi inhabiting small mountain streams.
AB  - Age, growth and reproductive characteristics of six westslope cutthroat trout
      Oncorhynchus clarkii lewisi populations were studied in the south-western Rocky
      Mountains in Alberta, Canada. Sagittal otoliths were collected from 605 fish
      ranging in size from 36 to 250 mm (fork length). The maximum detected age (13
      years for females and 12 for males) was higher than has been reported previously
      in published literature; but no significant differences in age distributions
      between males and females were found. Length growth rates, estimated using the
      von Bertalanffy growth function, showed that males and females had similar growth
      rates. Sex ratios varied between 0.3 to 2.0 females per male. Age and size at 50%
      maturity were greater for females than males (4.9 years and 139 mm v. 3.7 years
      and 125 mm). Mature females were yearly spawners with highly variable fecundities
      (mean +/- S.D. = 223 +/- 94) and their ovaries contained both developed and
      undeveloped eggs. Across all populations, mean instantaneous mortality rate (Z)
      was estimated as 0.555, annual survival rates for 0-1 year-old fish were 3.2 and
      57.4% for older fish. An altitudinal distribution gradient was observed, with
      older fish occupying upper stream reaches. This study provides a comprehensive
      evaluation of biological characteristics and structure of O. c. lewisi
      populations inhabiting small, mountain streams and should provide useful basic
      information for management policies of this threatened species in eastern
      drainage of the Canadian Rocky Mountains.

PMID- 30198206
TI  - Enantiomers separation by capillary electrochromatography using polysaccharide
      based stationary phases.
AB  - The separation of chiral compounds is an interesting and important topic of
      research because these compounds are involved in some biological processes,
      fundamentally in human health. Among the various application fields where
      enantiomers are remarkable, drug analysis has to be considered. Most of the drugs
      contain enantiomers and very often one of the two isomers could be
      pharmacologically more active or even dangerous. Therefore, the separation of
      these compounds is very important. Among the different analytical techniques
      usually employed, capillary electrochromatography has demonstrated great
      capability in enantiomers resolution. The great potential of this
      electromigration technique stands mainly in its high efficiency due to the use of
      an electrosmotic flow (flat flow profile) and on the high selectivity because of
      the use of a stationary phase. Chiral separation can be obtained utilizing
      several chiral stationary phases including a polysaccharide derivative. The aim
      of this review paper is to summarize the main features of capillary
      electrochromatography and polysaccharide derivatives of chiral stationary phase.
      It also report examples of practical applications utilizing this approach.

PMID- 30198207
TI  - Climate-based seed transfer of a widespread shrub: population shifts, restoration
      strategies, and the trailing edge.
AB  - Genetic resources have to be managed appropriately to mitigate the impact of
      climate change. For many wildland plants, conservation will require knowledge of
      the climatic factors affecting intraspecific genetic variation to minimize
      maladaptation. Knowledge of the interaction between traits and climate can focus
      management resources on vulnerable populations, provide guidance for seed
      transfer, and enhance fitness and resilience under changing climates. In this
      study, traits of big sagebrush (Artemisia tridentata) were examined among common
      gardens located in different climates. We focus on two subspecies, wyomingensis
      and tridentata, that occupy the most imperiled warm-dry spectrum of the sagebrush
      biome. Populations collected across the sagebrush biome were recorded for flower
      phenology and survival. Mixed-effects models examined each trait to evaluate
      genetic variation, environmental effects, and adaptive breadth of populations.
      Climate variables derived from population-source locations were significantly
      associated with these traits (P < 0.0001), explaining 31% and 11% of the flower
      phenology and survival variation, respectively. To illustrate our model and
      assess variability in prediction, we examine fixed and focal point seed transfer
      approaches to map contemporary and climate model ensemble projections in two
      different regions of the sagebrush biome. A comparison of seed transfer areas
      predicts that populations from warmer climates become more prevalent, replacing
      colder-adapted populations by mid-century. However, these warm-adapted
      populations are often located along the trailing edge, margins of the species
      range predicted to be lost due to a contraction of the climatic niche. Management
      efforts should focus on the collection and conservation of vulnerable populations
      and prudent seed transfer to colder regions where these populations are projected
      to occur by mid-century. Our models provide the foundation to develop an
      empirical, climate-based seed transfer system for current and future restoration
      of big sagebrush.

PMID- 30198208
TI  - Human bocavirus is detected in human placenta and aborted tissues.
AB  - BACKGROUND: To date, four human bocaviruses (HBoV) have been described. The most
      closely related viruses (bovine and canine parvoviruses) are associated with
      miscarriage in their hosts. The objective of this retrospective study was to
      determine the frequency of HBoV DNA in miscarriage. STUDY DESIGN: Tissue samples
      from 172 patients, in which miscarriage occurred, were included and tested with a
      published qPCR protocol. Positive PCRs were mutually confirmed by sequencing.
      RESULTS: 43 patients (25%) were positive for HBoV DNA. Of those, the majority of
      HBoV-positive samples were tissues from miscarriage (placenta: 6; aborted tissue
      products of conception: 37 specimens). The samples were not paired; either
      placental or aborted tissue was available. CONCLUSIONS: The results show that, as
      long as no animal model is available, the role of HBoV in the occurrence of
      miscarriage requires additional prospective studies in order to investigate its
      significance and causal involvements of this pathogen.

PMID- 30198209
TI  - Evaluation of Intra- and Interscanner Reliability of MRI Protocols for Spinal
      Cord Gray Matter and Total Cross-Sectional Area Measurements.
AB  - BACKGROUND: In vivo quantification of spinal cord atrophy in neurological
      diseases using MRI has attracted increasing attention. PURPOSE: To compare across
      different platforms the most promising imaging techniques to assess human spinal
      cord atrophy. STUDY TYPE: Test/retest multiscanner study. SUBJECTS: Twelve
      healthy volunteers. FIELD STRENGTH/SEQUENCE: Three different 3T scanner platforms
      (Siemens, Philips, and GE) / optimized phase sensitive inversion recovery (PSIR),
      T1 -weighted (T1 -w), and T2 *-weighted (T2 *-w) protocols. ASSESSMENT: On all
      images acquired, two operators assessed contrast-to-noise ratio (CNR) between
      gray matter (GM) and white matter (WM), and between WM and cerebrospinal fluid
      (CSF); one experienced operator measured total cross-sectional area (TCA) and GM
      area using JIM and the Spinal Cord Toolbox (SCT). STATISTICAL TESTS: Coefficient
      of variation (COV); intraclass correlation coefficient (ICC); mixed effect
      models; analysis of variance (t-tests). RESULTS: For all the scanners, GM/WM CNR
      was higher for PSIR than T2 *-w (P < 0.0001) and WM/CSF CNR for T1 -w was the
      highest (P < 0.0001). For TCA, using JIM, median COVs were smaller than 1.5% and
      ICC >0.95, while using SCT, median COVs were in the range 2.2-2.75% and ICC 0.79
      0.95. For GM, despite some failures of the automatic segmentation, median COVs
      using SCT on T2 *-w were smaller than using JIM manual PSIR segmentations. In the
      mixed effect models, the subject was always the main contributor to the variance
      of area measurements and scanner often contributed to TCA variance (P < 0.05).
      Using JIM, TCA measurements on T2 *-w were different than on PSIR (P = 0.0021)
      and T1 -w (P = 0.0018), while using SCT, no notable differences were found
      between T1 -w and T2 *-w (P = 0.18). JIM and SCT-derived TCA were not different
      on T1 -w (P = 0.66), while they were different for T2 *-w (P < 0.0001). GM area
      derived using SCT/T2 *-w versus JIM/PSIR were different (P < 0.0001). DATA
      CONCLUSION: The present work sets reference values for the magnitude of the
      contribution of different effects to cord area measurement intra- and
      interscanner variability. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 4.

PMID- 30198210
TI  - Radiotherapy for parotid IgG4-related disease.
AB  - We describe the use of radiotherapy for parotid IgG4-related disease (IgG4-RD),
      initially misdiagnosed as Kimura's disease, with sustained good partial response
      in a 37-year-old male. To the best of our knowledge, this is the first reported
      case of radiation for extra-orbital IgG4-RD, albeit inadvertently.

PMID- 30198211
TI  - Effect of free running wheel exercise on renal expression of parathyroid hormone
      receptor type 1 in spontaneously hypertensive rats.
AB  - An active lifestyle is generally recommended for hypertensive patients to prevent
      subsequent end-organ damage. However, experimental data on long-term effects of
      exercise on hypertension are insufficient and underlying mechanisms are not well
      understood. This study was aimed to investigate the effect of exercise on renal
      expression of parathyroid hormone-related protein (PTHrP) and parathyroid hormone
      receptor type 1 (PTHR1) in spontaneously hypertensive rats (SHR). Twenty-four
      rats started free running wheel exercise at the age of 1.5 months (pre
      hypertensive state) and proceeded for 1.5, 3.0, 6.0, and 10.0 months. Thirty rats
      kept under standard housing conditions were used as sedentary controls. Kidney
      function was assessed by measuring plasma creatinine levels and urine albumin-to
      creatinine ratios. Renal expression of PTHrP and PTHR1 was analyzed by qRT-PCR
      and western blot. Renal expression of PTHR1 was markedly increased between the
      6th and 10th months in sedentary rats and this increase was significantly lower
      in SHRs with high physical activity on mRNA (-30%) and protein level (-27%). At
      the same time, urine albumin-to-creatinine ratio increased (from 65 to 231 mg/g)
      but somehow lower in exercise performing SHRs (48-196 mg/g). Our data suggest
      that enhanced exercise, stimulated by allocation of a free running wheel, is
      associated with lower PTHR1 expression in SHRs and this may contribute to
      preserved kidney function.

PMID- 30198213
TI  - Potential roles of smell and taste in the orientation behavior of coral-reef fish
      larvae: insights from morphology.
AB  - An ontogenetic analysis of the olfactory organ and the number and distribution of
      internal taste buds was carried out in two neon gobies (Elacatinus lori and
      Elacatinus colini) with a goal of revealing morphological trends that might
      inform an understanding of the roles of olfaction and taste in larval orientation
      and settlement behavior. The pattern of development of the olfactory organ is
      unremarkable and enclosure of the olfactory epithelium occurs concurrently with
      metamorphosis and settlement in both species. Like other gobies, juvenile and
      adult E. lori and E. colini have one olfactory lamella, but they lack the
      accessory nasal sacs (present in some gobies) that could facilitate active
      olfactory ventilation (i.e., sniffing). A small number of taste buds are present
      at hatch with most found in the caudal region of the buccal cavity (on gill
      arches, roof of mouth). As taste bud number increases they demonstrate an
      anterior spread to the lips, buccal valves and tongue (i.e., basihyal). In the
      absence of an obvious ventilatory mechanism for the olfactory sacs, the water
      flows through the buccal cavity that occur with cyclic gill ventilation may allow
      the internal taste buds to play a role in chemical-mediated orientation and reef
      seeking behavior in larval fishes.

PMID- 30198212
TI  - ETA receptor activation contributes to T cell accumulation in the kidney
      following ischemia-reperfusion injury.
AB  - Renal ischemia-reperfusion (IR) injury and acute kidney injury (AKI) increase the
      risk of developing hypertension, with T cells suspected as a possible mechanistic
      link. Endothelin promotes renal T cell infiltration in several diseases,
      predominantly via the ETA receptor, but its contribution to renal T cell
      infiltration following renal IR injury is poorly understood. To test whether ETA
      receptor activation promotes T cell infiltration of the kidney following IR
      injury, male C57BL/6 mice were treated with the ETA receptor antagonist ABT-627
      or vehicle, commencing 2 days prior to unilateral renal IR injury. Mice were
      sacrificed at 24 h or 10 days post-IR for assessment of the initial renal injury
      and subsequent infiltration of T cells. Vehicle and ABT-627-treated mice
      displayed significant upregulation of endothelin-1 (ET-1) in the IR compared to
      contralateral kidney at both 24 h and 10 days post-IR (P < 0.001). Renal CD3+ T
      cell numbers were increased in the IR compared to contralateral kidneys at 10
      days, but ABT-627-treated mice displayed a 35% reduction in this effect in the
      outer medulla (P < 0.05 vs. vehicle) and a nonsignificant 23% reduction in the
      cortex compared to vehicle-treated mice. Whether specific T cell subsets were
      affected awaits confirmation by flow cytometry, but outer medullary expression of
      the T helper 17 transcription factor RORgammat was reduced by ABT-627 (P = 0.06).
      These data indicate that ET-1 acting via the ETA receptor contributes to renal T
      cell infiltration post-IR injury. This may have important implications for immune
      system-mediated long-term consequences of AKI, an area which awaits further
      investigation.

PMID- 30198214
TI  - An improved contrast equalization technique for contrast enhancement in scanning
      electron microscopy images.
AB  - In scanning electron microscopy (SEM), an intensive beam of electrons is utilized
      to generate high-quality images that can be used across scientific disciplines
      including biology and medicine. However, the images produced by different SEM
      devices are often degraded by a low-contrast effect as a result of various
      existing limitations. Hence, an improved contrast equalization technique is
      proposed in this article to ameliorate the contrast of SEM images and provide
      better visual quality results. The proposed technique consists of two major
      phases; the first includes a two-step regularization process used to regularize
      the intensities of the input image, while the second includes a two-step mapping
      process used to further improve the contrast and to remap image intensities to
      their natural dynamic range. The proposed technique is tested with many real
      degraded and synthetic-degraded SEM images, and its results are compared with six
      well-known contrast enhancement techniques. Accordingly, the comparison results
      are evaluated using four advanced image quality assessment metrics. Intensive
      experiments and comparisons exhibited the favorability of the proposed technique,
      in that it provided visually pleasing results with no visible flaws and
      outperformed the comparison techniques in terms of perceived quality and scored
      accuracy.

PMID- 30198215
TI  - Killing two bugs with one stone: a perspective for targeting multiple pest
      species by incorporating reproductive interference into sterile insect technique.
AB  - The sterile insect technique is an environmentally friendly method to control and
      even eradicate agricultural and veterinary insect pests without using chemical
      pesticides in excess. However, the continuous production and release of sterile
      insects is economically costly and eradication programs using sterile insects
      have not always been successful owing to the incomplete mating ability of the
      sterile insects. Here we focus on the theory and empirical findings of
      interspecific negative mating interaction, known as reproductive interference, to
      develop a more cost-effective and value-added pest management program. We suggest
      that sterile insects can be used for simultaneous control of both wild-type
      conspecifics and closely related pest species by taking advantage of the fact
      that, when species recognition abilities are incomplete, courtship and mating are
      often misdirected toward heterospecies. This new approach might help mitigate
      economic damage and human health crises caused by pest insects. (c) 2018 Society
      of Chemical Industry.

PMID- 30198216
TI  - Retinal vascular function in asymptomatic individuals with a positive family
      history of cardiovascular disease.
AB  - PURPOSE: To compare retinal microvascular function in healthy individuals with
      and without a positive family history (FH) of cardiovascular disease (CVD).
      METHODS: Retinal vessel reactivity was assessed by means of dynamic retinal
      vessel analysis in 38 healthy subjects aged between 30 and 66 years with a
      positive FH of CVD and 37 age- and gender-matched control subjects. Other
      assessments included blood pressure (BP) profiles, blood glucose and lipid
      metabolism markers, Framingham risk scores (FRS), carotid intima-media thickness
      (c-IMT) and brachial flow-mediated dilation (FMD). RESULTS: Family history
      positive subjects showed decreased retinal arterial baseline diameter
      fluctuation, dilation amplitude, percent dilation, and overall constriction
      response slope (p = 0.001; p = 0.015; p = 0.001; and p < 0.001, respectively) and
      increased percent constriction (p = 0.008). On the venous side, baseline
      corrected flicker response and dilation response slope were decreased in the FH
      positive group (p = 0.009 and p = 0.010, respectively). There were no significant
      differences between groups in c-IMT scores or FMD parameters (all p > 0.05). The
      arterial MC% correlated negatively with decreased high-density lipoprotein
      cholesterol (r = -0.52, p = 0.002) in only FH-positive group. CONCLUSION:
      Although macrovascular function is preserved in individuals with FH positive for
      CVD but with low FRS, there are, however, functional impairments at the retinal
      microvascular level that correlate with established plasma markers for
      cardiovascular risk.

PMID- 30198217
TI  - Effect of aerobic training on baseline expression of signaling and respiratory
      proteins in human skeletal muscle.
AB  - Most studies examining the molecular mechanisms underlying adaptation of human
      skeletal muscles to aerobic exercise focused on the response to acute exercise.
      Here, we examined the effect of a 2-month aerobic training program on baseline
      parameters in human muscle. Ten untrained males performed a one-legged knee
      extension exercise for 1 h with the same relative intensity before and after a 2
      month aerobic training program. Biopsy samples were taken from vastus lateralis
      muscle at rest before and after the 2 month training program (baseline samples).
      Additionally, biopsy samples were taken from the exercised leg 1 and 4 h after
      the one-legged continuous knee extension exercise. Aerobic training decreases
      baseline phosphorylation of FOXO1Ser256 , increases that of CaMKIIThr286 ,
      CREB1Ser133 , increases baseline expression of mitochondrial proteins in
      respiratory complexes I-V, and some regulators of mitochondrial biogenesis (TFAM,
      NR4A3, and CRTC2). An increase in the baseline content of these proteins was not
      associated with a change in baseline expression of their genes. The increase in
      the baseline content of regulators of mitochondrial biogenesis (TFAM and NR4A3)
      was associated with a transient increase in transcription after acute exercise.
      Contrariwise, the increase in the baseline content of respiratory proteins does
      not seem to be regulated at the transcriptional level; rather, it is associated
      with other mechanisms. Adaptation of human skeletal muscle to regular aerobic
      exercise is associated not only with transient molecular responses to exercise,
      but also with changes in baseline phosphorylation and expression of regulatory
      proteins.

PMID- 30198218
TI  - Abnormal Oculomotor Functions in Amyotrophic Lateral Sclerosis.
AB  - BACKGROUND AND PURPOSE: Although traditionally regarded as spared, a range of
      oculomotor dysfunction has been recognized in amyotrophic lateral sclerosis (ALS)
      patients. ALS is nowadays considered as a neurodegenerative disorder of a third
      compartment comprising widespread areas of extra-motor brain including
      cerebellum. Our objective was to perform an observational study to examine for
      ocular motor dysfunction in patients with ALS and for any differences between
      bulbar-onset and spinal-onset patients. METHODS: Thirty two ALS patients (bulbar
      onset: 10, spinal onset: 22) underwent the standardized systemic evaluations
      using video-oculography. RESULTS: Oculomotor dysfunctions such as square wave
      jerks, saccadic dysmetria, abnormal cogwheeling smooth pursuits and head shaking
      and positional nystagmus of central origin have been observed in the ALS patients
      at a relatively early stage. Abnormal smooth pursuits and saccadic dysmetria were
      increased in the bulbar-onset compared to the spinal-onset (p<0.05). CONCLUSIONS:
      These oculomotor abnormalities may be a marker of neuro-degeneration beyond motor
      neurons in ALS, especially in bulbar-onset disease. Future longitudinal studies
      of eye movement abnormalities have provided insights into the distribution and
      nature of the disease process.

PMID- 30198219
TI  - Region-Based Analysis of Prevalence and Incidence of Parkinson's Disease:
      Analysis of the National Sample Cohort in South Korea.
AB  - BACKGROUND AND PURPOSE: The rapid increases in the elderly population and
      urbanization in South Korea have influenced both demographics and the
      environment. This study investigated trends in the prevalence and incidence of
      Parkinson's disease (PD), and the associations of PD with the urban and rural
      environments in South Korea. METHODS: This study examined subjects aged 40 years
      or older in a cohort constructed using the National Sample Cohort data set in
      South Korea during 2002-2013. We estimated the age-standardized prevalence and
      incidence of PD based on the 2002 population, and estimated their trends. We
      analyzed regional differences in these rates by dividing South Korea into three
      regions based on geographic characteristics and two regions based on the degree
      of urbanization. RESULTS: The standardized prevalence rates of PD per 100,000
      increased significantly from 75.8 in 2003 to 136.8 in 2012 (p<0.0001), especially
      in older subjects. The standardized prevalence of PD was highest in metropolitan
      Seoul. The standardized incidence of PD per 100,000 was 13.9 in 2003 and 10.3 in
      2012, with no significant trend (p>0.05). The standardized incidence of PD in
      younger subjects was lower in eastern Korea than in the other two regions, while
      in the older subjects it was lower in western Korea than in metropolitan Seoul
      over almost the entire analyzed period. The standardized incidence of PD did not
      differ significantly between metropolitan and nonmetropolitan areas. CONCLUSIONS:
      The standardized prevalence of PD increased steadily from 2003 to 2012 in South
      Korea, while its standardized incidence has remained constant. There were
      regional differences in the prevalence and incidence of PD based on the degree of
      urbanization and the area of agricultural land.

PMID- 30198220
TI  - Multimodal Assessment of Neural Substrates in Computerized Cognitive Training: A
      Preliminary Study.
AB  - BACKGROUND AND PURPOSE: Several studies have validated the clinical efficacy of
      computerized cognitive training applications. However, few studies have
      investigated the neural substrates of these training applications using
      simultaneous multimodal neuroimaging modalities. We aimed to determine the
      effectiveness of computerized cognitive training and corresponding neural
      substrates through a multimodal approach. METHODS: Ten patients with mild
      cognitive impairment (MCI), six patients with subjective memory impairment (SMI),
      and 10 normal controls received custom-developed computerized cognitive training
      in the memory clinic of a university hospital. All of the participants completed
      24 sessions of computerized cognitive training, each lasting 40 minutes and
      performed twice weekly. They were assessed using neuropsychological tests (both
      computerized and conventional), electroencephalography, fluorodeoxyglucose
      positron-emission tomography (FDG-PET), volumetric magnetic resonance imaging
      (MRI), and diffusion-tensor imaging (DTI) at pre- and posttraining. RESULTS: The
      patients with MCI exhibited significant improvements in the trail-making test
      black & white-B, and memory domain of the computerized cognitive assessment.
      Subjects with normal cognition exhibited significant improvements in scores in
      the language and attention-/psychomotor-speed domains. There were no significant
      changes in subjects with SMI. In the pre- and posttraining evaluations of the MCI
      group, FDG-PET showed focal activation in the left anterior insula and anterior
      cingulate after training. Volumetric MRI showed a focal increase in the cortical
      thickness in the rostral anterior cingulate. DTI revealed increased fractional
      anisotropy in several regions, including the anterior cingulate. CONCLUSIONS: The
      anterior cingulate and anterior insula, which are parts of the salience network,
      may be substrates for the improvements in cognitive function induced by
      computerized cognitive training.

PMID- 30198221
TI  - Paroxysmal Dyskinesia in Children: from Genes to the Clinic.
AB  - BACKGROUND AND PURPOSE: Paroxysmal dyskinesia is a genetically and clinically
      heterogeneous movement disorder. Recent studies have shown that it exhibits both
      phenotype and genotype overlap with other paroxysmal disorders as well as
      clinical heterogeneity. We investigated the clinical and genetic characteristics
      of paroxysmal dyskinesia in children. METHODS: Fifty-five patients (16 from 14
      families and 39 sporadic cases) were enrolled. We classified them into three
      phenotypes: paroxysmal kinesigenic dyskinesia (PKD), paroxysmal nonkinesigenic
      dyskinesia (PNKD), and paroxysmal exercise-induced dyskinesia (PED). We sequenced
      PRRT2, SLC2A1, and MR-1 in these patients and reviewed their medical records.
      RESULTS: Forty patients were categorized as PKD, 14 as PNKD, and 1 as PED. Thirty
      eight (69.1%) patients were male, and their age at onset was 8.80+/-4.53 years
      (mean+/-SD). Dystonia was the most common symptom (38 patients, 69.1%).
      Pathogenic variants were identified in 20 patients (36.4%): 18 with PRRT2 and 2
      with SLC2A1. All of the patients with PRRT2 mutations presented with PKD alone.
      The 2 patients carrying SLC2A1 mutations presented as PNKD and PED, and one of
      them was treated effectively with a ketogenic diet. Six mutations in PRRT2
      (including 2 novel variants) were identified in 9 of the 13 tested families
      (69.2%) and in 8 patients of the 25 tested sporadic cases (32.0%). There were no
      significant differences in clinical features or drug response between the PRRT2
      positive and PRRT2-negative PKD groups. CONCLUSIONS: This study has summarized
      the clinical and genetic heterogeneity of paroxysmal dyskinesia in children. We
      suggest that pediatric paroxysmal dyskinesia should not be diagnosed using
      clinical features alone, but by combining them with broader genetic testing.

PMID- 30198223
TI  - A Novel Homozygous Variant of SETX Causes Ataxia with Oculomotor Apraxia Type 2.
AB  - BACKGROUND AND PURPOSE: Autosomal recessive cerebellar ataxias constitute a
      highly heterogeneous group of neurodegenerative disorders. This study was carried
      out to determine the clinical and genetic causes of ataxia in two families from
      Pakistan. METHODS: Detailed clinical investigations were carried out on probands
      in two consanguineous families. Magnetic resonance imaging was performed. Exome
      sequencing data were examined for likely pathogenic variants. Candidate variants
      were checked for cosegregation with the phenotype using Sanger sequencing. Public
      databases including ExAC, GnomAD, dbSNP, and the 1,000 Genome Project as well as
      ethnically matched controls were checked to determine the frequencies of the
      alleles. Conservation of missense variants was ensured by aligning orthologous
      protein sequences from diverse vertebrate species. RESULTS: Reverse phenotyping
      identified spinocerebellar ataxia, autosomal recessive 1 [OMIM 606002, also
      referred to as ataxia oculomotor apraxia type 2 (AOA2)] and ataxia telangiectasia
      (OMIM 208900) in the two families. A novel homozygous missense mutation c.202 C>T
      (p.Arg68Cys) was identified within senataxin, SETX in the DNA of both patients in
      one of the families with AOA2. The patients in the second family were homozygous
      for a known variant in ataxia-telangiectasia mutated (ATM) gene: c.7327 C>T
      (p.Arg2443Ter). Both variants were absent from 100 ethnically matched control
      chromosomes and were either absent or present at very low frequencies in the
      public databases. CONCLUSIONS: This report extends the allelic heterogeneity of
      SETX mutations causing AOA2 and also presents an asymptomatic patient with a
      pathogenic ATM variant.

PMID- 30198222
TI  - Consolidation of a Learned Skill Correlates with Dopamine SPECT Uptake in Early
      Parkinson's Disease.
AB  - BACKGROUND AND PURPOSE: Basal ganglia play a pivotal role in procedural memory.
      However, the correlation between skill learning and striatal 123I-ioflupane
      uptake in Parkinson's disease (PD) has not been reported previously. Our
      objective was to determine whether visuomotor skill learning is associated with
      striatal 123I-ioflupane uptake in early PD. METHODS: We designed a case-control
      study to assess learning and consolidation of a visuomotor learning task
      (mirrored drawing of star-shaped figures) performed on two consecutive days by
      early-PD patients (disease duration <2 years) and age-matched healthy subjects.
      Outcomes were the error rate and time per trial, as well as performance indices
      to assess the relative improvement on the first day (learning) and the retention
      on the second day (consolidation). For PD patients, we evaluated the correlation
      of skill learning with semiquantitative 123I-ioflupane uptake. RESULTS: We
      included 9 PD patients and 10 control subjects with the same baseline
      characteristics (age, male/female ratio, educational level, Mini Mental State
      Examination score, and Hospital Anxiety and Depression Scale score, all p>0.18)
      other than the score on part III of the Movement Disorders Society Unified
      Parkinson's Disease Rating Scale, which was higher in the PD patients (mean+/-SD:
      15.0+/-10.4 vs. 1.3+/-1.1, p<0.001). The learning indices were the same in the
      two groups (p>0.5), whereas PD patients showed a lower consolidation index for
      the time per trial (p=0.009). Moreover, this performance was correlated with
      uptake in the right caudate nucleus (Spearman's rho=0.82, p=0.007) and the right
      striatum (Spearman's rho=0.67, p=0.049), including when multiple linear
      regression adjusting for the levodopa equivalent daily dose was performed
      (p=0.005 for the caudate nucleus and p=0.024 for the striatum). CONCLUSIONS: This
      study provides evidence of a correlation between procedural memory impairment and
      striatal dopaminergic dysfunction in early PD.

PMID- 30198224
TI  - Changes in the Multiple Sclerosis Treatment Paradigm. What Do We Do Now and What
      Were We Doing Before?
AB  - BACKGROUND AND PURPOSE: The number of disease-modifying drugs (DMDs) available
      for treating relapsing-remitting multiple sclerosis is increasing. Numerous drugs
      have been approved since 2010 in South America, which has increased the
      complexity of the treatment algorithm. The aim of this study was to determine the
      changes in multiple sclerosis treatments relative to the underlying causes and
      the availability of new DMDs in Argentina. METHODS: A descriptive retrospective
      study was carried out on a group of 59 patients diagnosed with RRMS who use more
      than one DMD. RESULTS: The first treatment switch occurred before 2010 in 27% of
      the patients and after 2010 in the other 73%. Efficacy was the main reason for
      switching during both periods. A second treatment switch was required in 25% of
      the patients, with this occurring after 2010 in 86.6% of them. Interferon was the
      most-used drug before 2010 and fingolimod was the most-used drug thereafter.
      CONCLUSIONS: We have identified that the tendency for treatment changes has
      increased following the arrival of new drugs. Efficacy has been the main cause of
      these changes.

PMID- 30198226
TI  - Therapeutic Interventions in Adult Low-Grade Gliomas.
AB  - Treating adult low-grade gliomas (LGGs) is particularly challenging due to the
      highly infiltrative nature of this type of brain cancer. Although surgery,
      radiotherapy, and chemotherapy are the mainstay treatment modalities for LGGs,
      the optimal combination management plan for a particular patient based on
      individual symptoms and the risk of treatment-induced toxicity remains unclear.
      This review highlights the competency and limitations of standard treatment
      options while providing an essential therapeutic update regarding current
      clinical trials aimed at implementing targeted therapies with morbidity rates
      lower than those for current LGG treatments and also augmenting the killing of
      cancerous cells while maintaining an improved quality of life.

PMID- 30198225
TI  - The Role of Information Processing Speed in Clinical and Social Support Variables
      of Patients with Multiple Sclerosis.
AB  - BACKGROUND AND PURPOSE: Information processing speed is one of the most impaired
      cognitive functions in multiple sclerosis (MS). There are two tests widely used
      for evaluating information processing speed: the Symbol Digit Modalities Test
      (SDMT) and the Paced Auditory Serial Addition Test (PASAT). To analyze the
      relationship between processing speed and the clinical and social support
      variables of patients with MS. METHODS: A group of 47 patients with relapsing
      remitting MS was studied, 31 were women and 16, men. Age: 39.04+/-13.17, years of
      schooling: 13.00+/-3.87, Expanded Disability Status Scale (EDSS): 2.78+/-1.81,
      and disease evolution: 8.07+/-6.26. Instruments of measure; processing speed:
      SDMT, PASAT, clinical variables: EDSS, Fatigue Severity Scale (FSS), Beck's
      Depression Inventory II (BDI-II), and social support: Medical Outcomes Study
      Social Support Survey (MOS). RESULTS: Significant correlations were found between
      information processing speed and psychiatric, motor disability and social support
      variables. The SDMT correlated significantly and negatively with BDI-II, FSS,
      EDSS, and MOS (p<0.05), whereas the PASAT correlated negatively with FSS and
      positively with MOS (p<0.05). Information processing speed appeared as the
      performance predictor of these variables. The SDMT produced significant changes
      in EDSS (R2=0.343, p=0.000); FSS (R2=0.109, p=0.031); BDI-II (R2=0.124, p=0.018),
      and MOS (R2=between 0.212 and 0.379, p<0.05). CONCLUSIONS: Information processing
      speed has influence on the clinical variables and the social support of patients
      with MS. These aspects are important to bear in mind for therapeutic approach.

PMID- 30198227
TI  - Neuromonitoring for Spinal Cord Stimulation Lead Placement Under General
      Anesthesia.
AB  - Spinal cord stimulation (SCS) is a common therapeutic technique for treating
      medically refractory neuropathic back and other limb pain syndromes. SCS has
      historically been performed using a sedative anesthetic technique where the
      patient is awakened at various times during a surgical procedure to evaluate the
      location of the stimulator lead. This technique has potential complications, and
      thus other methods that allow the use of a general anesthetic have been
      developed. There are two primary methods for placing leads under general
      anesthesia, based on 1) compound muscle action potentials and 2) collisions
      between somatosensory evoked potentials. Both techniques are discussed, and the
      literature on SCS lead placement under general anesthesia using intraoperative
      neurophysiological mapping is comprehensively reviewed.

PMID- 30198228
TI  - Association between Frontal-Executive Dysfunction and Speech-in-Noise Perception
      Deficits in Mild Cognitive Impairment.
AB  - BACKGROUND AND PURPOSE: Speech-in-noise perception deficits have been
      demonstrated in patients with mild cognitive impairment (MCI). However, it
      remains unclear whether the impairment of speech perception varies between MCI
      subtypes. The purpose of this study was twofold: 1) to compare speech perception
      performance among MCI subgroups, and 2) to identify the cognitive domains
      specifically related to speech-in-noise perception. METHODS: We studied 46
      patients with MCI and 39 hearing-threshold-matched cognitively normal elderly
      (CNE) subjects. Two different patient classifications were used: 1) patients with
      amnestic mild cognitive impairment (aMCI) (n=21) or nonamnestic mild cognitive
      impairment (naMCI) (n=25), and 2) patients with frontal-executive dysfunction
      (FED) (n=16) or without FED (n=30). All of the subjects underwent audiometric,
      neuropsychological, and speech perception assessments. Speech-in-noise perception
      was measured using sentence recognition tests in the presence of two types of
      background noise at four levels. RESULTS: First, as the level of background noise
      increased, the MCI with FED group scored lower than both the MCI without FED and
      CNE groups under both types of noise. Second, both the naMCI and aMCI groups
      scored lower than the CNE group, but there were no differences between the naMCI
      and aMCI groups in sentence recognition under any noise conditions. Third,
      significant correlations were found between sentence recognition and executive
      function scores both in the MCI groups and in the CNE group. CONCLUSIONS: Our
      findings suggest that frontal-executive function is strongly related to speech-in
      noise perception and that MCI patients with FED have greater deficits in speech
      in-noise perception compared to other subgroups of MCI.

PMID- 30198229
TI  - Factors Associated with Cheyne-Stokes Respiration in Acute Ischemic Stroke.
AB  - BACKGROUND AND PURPOSE: Cheyne-Stokes respiration (CSR) is frequently observed in
      patients with acute stroke. There have been conflicting opinions about the
      associations of CSR with the location and size of the lesion. We aimed to better
      define the clinical relevance and pathogenesis of CSR in acute stroke. METHODS:
      We investigated patients who had been admitted with acute ischemic stroke and
      received an overnight sleep apnea test. We collected data on demographics, risk
      factors, etiologic subtypes, initial vital signs, clinical course of the stroke,
      and parameters associated with respiratory events during the sleep apnea test. We
      performed a multivariate logistic regression analysis to determine the factors
      associated with CSR. RESULTS: Among 182 patients, 35 patients showed CSR in sleep
      apnea testing. Large-artery atherosclerosis or cardioembolism, bilateral
      hemispheric involvement, atrial fibrillation, low left-ventricle ejection
      fraction (LVEF), and left atrium (LA) enlargement were all associated with the
      presence of CSR. Multivariate analysis revealed that the previous modified Rankin
      Scale (mRS) score, bilateral hemispheric involvement, low LVEF, and LA
      enlargement were significantly associated with CSR. Subgroup analysis with large
      artery atherosclerosis without cardiac disease revealed that the previous mRS
      score is the only independent factor associated with CSR. CONCLUSIONS: CSR
      frequently occurs in strokes involving large arteries or due to cardioembolism,
      regardless of the location and severity of the stroke. Predisposing conditions
      such as preexisting neurologic disability, low LVEF, and LA enlargement are
      associated with CSR in acute stroke.

PMID- 30198230
TI  - Muscle Thickness and Echo Intensity of the Abdominal and Lower Extremity Muscles
      in Stroke Survivors.
AB  - BACKGROUND AND PURPOSE: This study compared the muscle thickness (MT) and echo
      intensity (EI) of the abdominal, thigh, and lower leg muscles between the paretic
      and nonparetic sides in chronic stroke survivors. METHODS: Thirty-two stroke
      survivors living in the community participated in this study. The MT and EI,
      which are indicators of muscle mass and intramuscular fat or connective tissue,
      were assessed in the rectus abdominis, external oblique, internal oblique,
      transversus abdominis, rectus femoris, vastus intermedius, vastus lateralis,
      vastus medialis, tibialis anterior, gastrocnemius, and soleus via transverse
      ultrasound imaging. In addition, a possible indicator of physical activity-the
      frequency of going out per week-was evaluated. RESULTS: All quadriceps muscles
      and the tibialis anterior were significantly thinner and the EI values of the
      vastus intermedius, vastus lateralis, vastus medialis, and soleus were
      significantly higher in the paretic limb than the nonparetic limb. The MT and EI
      values of abdominal muscles did not differ significantly between the two sides.
      The MT values of the paretic rectus femoris, vastus lateralis, and vastus
      medialis were significantly associated with the frequency of going out after
      adjusting confounding factors. The MT of the nonparetic vastus lateralis was
      significantly associated with latency from stroke onset after adjusting
      confounding factors. CONCLUSIONS: Our results indicate that quantitative and
      qualitative changes on the paretic side in stroke survivors were the most robust
      in the thigh muscles, whereas such changes might not occur in the abdominal
      muscles.

PMID- 30198231
TI  - Effects of Antiepileptic Drugs on Language Abilities in Benign Epilepsy of
      Childhood with Centrotemporal Spikes.
AB  - BACKGROUND AND PURPOSE: This study is to assess the responsiveness of
      electroencephalography (EEG) abnormalities and their effects on language ability
      after initiating different types of antiepileptic therapy in children with newly
      diagnosed benign epilepsy of childhood with centrotemporal spikes (BECTS).
      METHODS: The records of patients newly diagnosed with BECTS (n=120; 69 males)
      were reviewed retrospectively. The patients were randomly treated with
      lamotrigine, oxcarbazepine, or topiramate monotherapy, and underwent at least two
      EEG and standardized language tests. Effects were compared using Pearson's chi
      square tests and paired t-tests. RESULTS: The recurrence rates for seizures in
      the lamotrigine, topiramate, and oxcarbazepine groups were 19.4%, 21.7%, and
      11.4%, respectively, while complete or partial recovery (as indicated by EEG)
      occurred in 32%, 39%, and 16% of the patients. Patients in the lamotrigine group
      showed significant improvements in all parameters assessed by the Test of
      Language Problem Solving Abilities, except for 'determining cause.' Patients in
      the oxcarbazepine group also showed improvements, except for 'making inferences'
      (p<0.05). Most linguistic index scores were worse in the topiramate group except
      for Mean Length of Utterance in Words. Patients in the lamotrigine and
      oxcarbazepine groups showed significant improvements in the receptive language
      test (p<0.05). EEG improvements were not related to language ability.
      CONCLUSIONS: The improvements in language and problem-solving performance in
      children with BECTS were greater for lamotrigine and oxcarbazepine than for
      topiramate. However, EEG remission did not imply that language function would be
      improved after the treatments.

PMID- 30198232
TI  - Characteristics of South Korean Patients with Hereditary Transthyretin
      Amyloidosis.
AB  - BACKGROUND AND PURPOSE: This retrospective cross-sectional study included 18
      patients from unrelated families harboring mutations of the transthyretin gene
      (TTR), and analyzed their characteristics and geographical distribution in South
      Korea. METHODS: The included patients had a diagnosis of systemic amyloidosis,
      clinical symptoms, such as amyloid neuropathy or cardiomyopathy, and confirmation
      of a TTR gene mutation using genetic analysis recorded between April 1995 and
      November 2014. RESULTS: The mean age at disease onset was 49.6 years, and the
      mean disease duration from symptom onset to diagnosis was 3.67 years. Fifteen of
      the 18 patients were classified as mixed phenotype, 2 as the neurological
      phenotype, and only 1 patient as the cardiac phenotype. The most-common mutation
      pattern in South Korea was Asp38Ala, which was detected in eight patients.
      Thirteen patients reported their family hometowns, and five of the eight
      harboring the Asp38Ala mutation were from the Gyeongsang province in southeast
      Korea. The other eight patients exhibited a widespread geographical distribution.
      A particularly noteworthy finding was that the valine at position 30 (Val30Met)
      mutation, which was previously reported as the most-common TTR mutation worldwide
      and also the most common in the Japanese population, was not detected in the
      present South Korean patients. CONCLUSIONS: South Korean patients with hereditary
      TTR amyloidosis exhibited heterogeneous TTR genotypes and clinical phenotypes.
      The findings of this study suggest that the distribution of TTR amyloidosis in
      South Korea is due to de novo mutations and/or related to the other countries in
      East Asia.

PMID- 30198234
TI  - Determining the Etiology of Internuclear Ophthalmoplegia in a Patient with a
      Cardiac Pacemaker and Complex Neurological Presentation.

PMID- 30198235
TI  - Safe Childbirth after Taking Teriflunomide in a Woman with Multiple Sclerosis.

PMID- 30198233
TI  - Clinical Predictors of Excessive Daytime Sleepiness in Patients with Parkinson's
      Disease.
AB  - BACKGROUND AND PURPOSE: Excessive daytime sleepiness (EDS) is a common complaint
      among patients with Parkinson's disease (PD). Several factors have been
      associated with EDS in PD, especially neuropsychiatric symptoms. This study aimed
      to determine the relationships between neuropsychiatric symptoms,
      sociodemographic and clinical parameters, and EDS in PD. METHODS: This cross
      sectional study analyzed 85 patients with PD. All patients underwent
      socioeconomic and clinical data evaluations followed by a psychiatric interview
      and a neurological examination, including the assessment of sleep features.
      Patients were divided into two groups according to the presence or absence of
      EDS, which was defined as a score higher than 10 on the Epworth Sleepiness Scale.
      Binary logistic regression was performed in order to describe the predictors of
      EDS. RESULTS: We found that EDS affects 40% of PD patients and is associated with
      older age, restless legs syndrome, depressive and anxious symptoms, and worse
      sleep quality. In the multivariate analysis, older age, levodopa use, and worse
      sleep quality remained as significant predictors of EDS in PD. CONCLUSIONS:
      Nighttime sleep problems, older age, and levodopa use are significantly
      associated with EDS in PD. A careful assessment and the management of sleep
      problems in PD patients might help to improve their quality of life.

PMID- 30198236
TI  - GNE Myopathy with Prominent Axial Muscle Involvement.

PMID- 30198237
TI  - Giant Cell Arteritis Associated Arteritic Anterior Ischemic Optic Neuropathy:
      Sudden Vision Loss on the Contralateral Side of Headache.

PMID- 30198238
TI  - Factors influencing the accuracy of the denitrifier method for determining the
      oxygen isotopic composition of nitrate.
AB  - The denitrifier method is widely used as a novel pretreatment method for the
      determination of nitrogen and oxygen isotope ratios as it can provide
      quantitative and high-sensitivity measurements. Nevertheless, the method is
      limited by relatively low measurement accuracy for delta18O. In this study, we
      analyzed the factors influencing the accuracy of delta18O determination, and then
      systematically investigated the effects of dissolved oxygen concentrations and
      nitrate sample sizes on estimates of the delta15N and delta18O of nitrate
      reference materials. The delta18O contraction ratio was used to represent the
      relationship between the measured difference and true difference between two
      reference materials. We obtained the following main results: (1) a gas-liquid
      ratio of 3:10 (v/v) in ordinary triangular flasks and a shaking speed of 120
      r/min produced an optimal range (1.9 to 2.6 mg/L) in the concentration of
      dissolved oxygen for accurately determining delta18O, and (2) the delta18O
      contraction ratio decreased as nitrate sample size decreased within a certain
      range (1.0 to 0.1 MUmol). Our results suggested that delta18O contraction is
      influenced mainly by dissolved oxygen concentrations in pure culture, and
      provided a model for improving the accuracy of oxygen isotope analysis.

PMID- 30198239
TI  - Parkinson's disease: symptoms, treatment options and nursing care.
AB  - Idiopathic Parkinson's disease (IPD) is a progressive neurodegenerative condition
      that causes various motor and non-motor symptoms and will often have life
      changing effects for those with the condition, as well as for their family and
      carers. Nurses can make a significant difference to the lives of those affected
      by Parkinson's disease, whether in the acute setting, community setting or in
      care homes. This article explores the causes and progressive clinical pathway of
      IPD using an evidence-based approach. It emphasises the valuable role of the
      multidisciplinary team and of the nurse, in particular, in monitoring and
      improving the quality of life of those with the condition and their family and
      carers.

PMID- 30198240
TI  - [Review on the Methodology for Optical Parameter Extraction with Terahertz Time
      Domain Spectroscopy].
AB  - Optical parameters which macroscopically characterize optical properties of
      materials indirectly reflect microscopic peculiarities of materials. Accurate
      extractions of optical parameters are significant for the research of microscopic
      behavior and macroscopic responses of materials. In recent years, as a new
      spectral analysis method, terahertz time-domain spectroscopy (THz-TDS) technology
      has become a research hotspot. Due to the low THz radiation energy and narrow
      pulse width (picosecond range), THz-TDS technology is nondestructive with high
      temporal-resolution when being used to extract optical parameters of samples.
      This paper summarizes optical parameters extraction methods by using THz
      transmission and reflection spectroscopy technology, emphatically introduces
      several classic methods and analyses, along with their respective merits and
      demerits, and finally discusses the challenges of THz-TDS technology in optical
      parameters extraction. In conclusion, the transmission methods are adaptive for
      measuring substances which slightly absorb terahertz radiation, whereas the
      reflection methods are suitable for measuring materials with strong absorption
      capacity.

PMID- 30198241
TI  - [Study on the Turning Effect of the Energy Gap of pi Electron on Atomic Vibration
      in Conjugated Linear Polymer].
AB  - The Visible absorption and Raman spectra of beta-carotene were measured in
      dimethyl sulfoxide in temperature ranging from 81 to 25 C and in carbon disulfide
      in pressure range from 0.04 to 0.60 GPa, respectively. The results indicated that
      the visible absorption and Raman spectra are both red-shifted, Raman scattering
      cross section increase with the temperature decreasing. And with the pressure
      increasing, the visible absorption spectra are red-shifted, but the frequency
      shift towards higher frequencies in the Raman spectra, the Raman scattering cross
      section decrease unexpectedly. The latter can't be explained by the model of
      "effective conjugation length" and "coherent weakly damped electron-lattice
      vibrations". In this paper, we combined electron-vibration coupling rule with
      theoretical calculations and found that the electron-phonon coupling constant had
      a certain changing trend with the temperature and pressure variation, which
      Indicate that the interaction between pi-electron and CC bond vibration was
      essential for this experiment result. Thus, the turning effect of energy gap of
      the pi on CC vibration mode is responsible for such phenomenon.

PMID- 30198242
TI  - [FUNCTIONAL INTERACTION BETWEEN THE DOPAMINE AND MELANOCORTIN SYSTEMS IN THE
      BRAIN].
AB  - The brain melanocortin system plays a key role in the regulation of energy
      metabolism and feeding behavior and is involved in memory formation, and its
      abnormalities lead to metabolic disorders and cognitive deficit. The brain
      dopamine system controls the motor activity, the functions of the nervous,
      endocrine and cardiovascular systems, and is also involved in the regulation of
      peripheral metabolism and feeding behavior and in the formation of effect of
      reward and reinforcement. The fact that a large number of the important
      physiological functions are controlled by the melanocortin and dopamine systems
      indicates a close functional relationship between them in different areas of the
      brain. The basis of this relationship is colocalization of the components of
      melanocortin and dopamine signaling systems in neurons and interaction between
      them, which ensures a cross-talk between melanocortin and dopamine pathways in
      the CNS. The review includes a comprehensive analysis of the current state of the
      problem concerning the interaction between the melanocortin and dopamine systems
      of the brain at both the structural and functional levels.

PMID- 30198243
TI  - [Application Progress of Holographic Lithgraphy in Fabrication of Micro-Nano
      Photonic Structures].
AB  - Micro-nano photonic structures are developing vigorously based on the progress of
      photonics, semiconductor physics and microfabrication technology. A series of
      results are achieved in structure characterization, theory, and fabrication of
      them. Most high quality photonic structures are man-made ones; however, there are
      still some challenges in fabricating artificial large-area and high-quality
      photon materials. With the advantages of photonic structure processing
      technology, holographic lithography, a low-cost, time-saving and high-efficiency
      microfabrication method, performs superior application potentials in making
      metamaterials as well as photonic crystal templates. In this article, we
      introduced the principles of holographic lithography and described the
      applications in fabricating various micro-nano photonic structures, such as three
      dimensional face-center-cubic, wood-pile, diamond-like photonic crystals, as well
      as quasi-crystalline structure, chiral metamaterials and periodic defect-mode
      structures. Moreover, the applications of some structures in solar cell and
      optical fiber sensing are discussed. The success of fabricating micro-nano
      photonic structures by holographic lithography would pave the way for more
      applications of these structures in wide fields.

PMID- 30198244
TI  - [THE ROLE OF FIBROBLAST GROWTH FACTOR 21 (FGF21) IN THE REGULATION AND CORRECTION
      OF CARBOHYDRATE AND LIPID METABOLISM].
AB  - Identification of the natural metabolic factors that are able to normalize
      insulin sensitivity and carbohydrate and lipid metabolism is necessary for the
      development of pharmacological approaches for the correction of obesity and Type
      II diabetes. Fibroblast growth factor 21 (FGF21) is an atypical member of the FGF
      family that functions as an endocrine hormone which regulates carbohydrate and
      lipid metabolism. It is involved in maintaining of energy homeostasis and
      adaptation to starvation and low temperature. In rodents, FGF21 administration
      increases energy expenditure, reduces body weight, fat mass, blood glucose and
      insulin levels, and improves insulin sensitivity. Pharmacologically, FGF21 is a
      promising new clinical candidate for the treatment of diabetes and obesity. This
      review highlights recent advances in our understanding ofmechanisms of FGF21's
      physiologic and pharmacologic anti-diabetic actions.

PMID- 30198245
TI  - [ENDOTHELIAL DYSFUNCTION AND OBSTRUCTIVE LUNG PATHOLOGY].
AB  - Relationship of endothelial dysfunction and obstructive pulmonary diseases is a
      complex and poorly understood. Vascular endothelium is a multifunctional
      autonomous endocrine organ. The review discusses the various functions of the
      endothelium, causes, mechanisms and possible markers of endothelial dysfunction.
      The contribution of pulmonary vessel endothelial dysfunction in the initiation
      and progression of chronic obstructive pulmonary disease and asthma is
      considered. The existing approaches to the restoration of the structural and
      functional integrity of the vascular endothelium are discussed.

PMID- 30198246
TI  - [Optical Properties of Ag-Al Nanosphere Heterodimer].
AB  - Metal nanostructure material has attracted great attention due to its surface
      plasmon resonance. The optical properties of heterodimer metallic nanostructure
      materials are different compared with that of homogeneous nanostructure materials
      because their symmetry structure is broken. The symmetry of the original
      structures will be changed, and the interaction between the two particles will
      produce Fano resonance. The Fano resonances are the result of the double or more
      surface plasmon resonances coupling, and be controlled by properly controlling
      the nanostructures. The electric field enhancement and the radiation
      characteristics of the nanostructure are further optimized for the Fano resonance
      controlled. Aluminum nanostructure materials have become the best choice of the
      surface plasmon resonance in the UV region, because gold, silver and other noble
      metals have inter-band transition effects. In this work, we study the local field
      and absorption spectra of heterodimer composed of a silver nanosphere and an
      aluminum nanosphere by the Finite-Difference Time-Domain (FDTD) theory. Firstly,
      the effects of the incident polarization, the geometric like, nanospheres
      separation, nanosphere radius and physical dielectric media on the optical
      response of silver-aluminum nanospheres heterodimer are analyzed. Secondly, the
      near field distributions of heterodimer are given in-depth discussion. Due to the
      destruction of the symmetry of dimer material, heterodimeric optical character is
      significantly different from homodimer. Fano resonances are produced in UV and
      visible light in the heterodimer respectively when silver-aluminum nanospheres
      heterodimer is illuminated by the Y-polarized light. More favorable Fano
      resonance effects can be obtained by regulating the spacing and size of
      heterodimer in the given dielectric environment which is also an effect factor
      certainly. Finally, the absorption of the heterodimer contributed from each
      nanosphere structure is also analyzed. In this way, the result which is a general
      and complete description of the optical properties of silver-aluminum nanospheres
      heterodimer nanostructure in the paper, leads to the suppression and enhancement
      of the surface plasmon resonance in different frequency bands and may be valuable
      for the design and development of plasmonic devices and optical tools in UV
      visible light and could serve as the basis of the future experimental analysis of
      surface enhanced spectroscopy, molecular detection and biosensor etc.

PMID- 30198247
TI  - [EXISTENTIAL ORGANIZATION OF BRAIN BIOELECTRICAL ACTIVITY OF THE OFFSPRING OF
      RATS AFTER VITAL STRESS].
AB  - An association was found between severity of behavioral disturbances in the
      offspring of rats that survived the stress, and changing spatial-temporal
      organization of the ECOG. The proportion of synchronous activity in the right
      frontal and left occipital regions with respect to the right nape, and between
      the frontal leads increases with the minimum deviations of behavior. The
      proportion of ahead activity increased in frontal leads; reduced the share of
      lagging and an increasing proportion of synchronous bioelectrical activity in
      relation to the right occipital region in case of serious disorders of behavior.

PMID- 30198248
TI  - [THE INFLUENCE OF THE MELATONIN ON THE CORRELATION BETWEEN THE INTENSITY OF THE
      ACCUMULATION OF THE OXIDATI-VE-MODIFIED PROTEINS CONTENT, ACTIVITY OF THE
      ANTIOXIDANT ENZYMES AND THE STATE OF PROTEOLYSIS IN THE BASAL NUCLEI OF THE BRAIN
      UNDER THE ACUTE HYPOXIA].
AB  - The effect of melatonin on the correlation between the intensity of the
      accumulation of the oxidative-modified protein content, activity of the
      antioxidant enzymes and the state of proteoly-sis in the basal nuclei (the
      nucleus caudatus, globus pallidus, nucleus accumbens, amigdaloid complex) of the
      brain under the conditions of acute hypoxia has been studied. Under the
      conditions of acute hypoxia in the basal nuclei an intensification of the protein
      peroxidation processes is observed, the activity of the antioxidant enzymes
      decreases, the intensity of the proteolysis increases. The injection of melatonin
      in a dose of 1 mg per kg of the body mass before the modeling of acute hypoxia
      results in the decreasing of protein peroxidation, increasing of the antioxidant
      enzyme activity and normalization of the parameters of proteolysis.

PMID- 30198249
TI  - [The Acceleration of Monte Carlo Simulation for Optical Transmission in Large
      Space Biological Tissue].
AB  - Typically, it is time-consuming to use Monte Carlo simulation to model light
      propagation in turbid media, such as breasts, mainly because of the thick
      simulated tissue and the large number of photons required by the stochastic
      nature of MC simulations. In this paper, in view of the light source and the
      receiver in a straight line, the transmitted light received by optical fiber
      model is analyzed; in terms of the optical properties of biological tissue
      itself, implementation of boundary constraint conditions and restriction of the
      number of backscatter events have been developed to reduce the simulation time.
      It is verified that the calculation is relatively simple by many experiments,
      when the position after two scattering is regarded as the demarcation and the
      boundary constraint conditions are efficiently solved by optical parameters of
      tissue respectively. At the same time, considering the actual situation in
      incident and emergent position, the boundary constraint conditions are expanded.
      The number of backscatter of every photon that received by optical fiber in the
      same position are recorded and tissues are selected different thickness and the
      similar optical parameters in the simulations. Additionally, it is found that the
      number of backscatter would increase as the depth of tissue or scattering
      coefficient increases, or as absorption coefficient or anisotropic factor
      decreases. Therefore, the time is saved further through limiting the number of
      backscatter. The simulation results show the combination of those new methods
      reduces the operation time of the MC simulation by 50% on a typical desktop
      computer. Those new methods are especially suitable for MC simulations of the
      thick tissue or the scatterer with a complex boundary. This acceleration method
      is applicable when light source and receiver are in a straight line the
      biological tissue is thicker and scattering coefficient is large. It can
      effectively save needed time and be beneficial to analyze the transmission
      imaging.

PMID- 30198250
TI  - [BIOCHEMICAL CHARACTERISTICS OF BLOOD SERA IN DOMINANT AND SUBORDINATE RHESUS
      MONKEY MALES].
AB  - Study of relationship between the biochemical characteristics of blood serum from
      rhesus monkeys and their social rank was carried out. Some biochemical
      characteristics, first of all the content of urea and creatinine, the activity of
      aspartateaminotransferase and alkaline phosphatase were positively correlated
      with a relative rank of males, and negatively - with their weight. The body
      weight of dominant males was significantly lower than that of subordinate males.
      The data obtained show a significant variation in the characteristics of
      biochemical metabolism in subordinate and dominant males whose origin is
      determined by the features of feeding of high and low rank males, as well as by
      different level of stress experienced by the animals with different social rank.

PMID- 30198251
TI  - [Measurement of Soot Yield from the Pyrolysis of Toluene at High Temperatures by
      Laser Extinction Method].
AB  - The measurement system for the detection of soot production as high-temperature
      pyrolysis of hydrocarbon fuels behind the reflected shock wave was established.
      By using the laser extinction method, the soot yields of toluene/argon mixtures
      were measured at high temperatures. The mole fractions of toluene were 0.25% and
      0.5% while the pressures were approximate 2 and 4 atm. The temperatures ranged
      from 1 630 to 2 273 K. The dependence of soot yield on the temperature, pressure
      and fuel concentration was obtained. With the changes of temperature, the soot
      yield is a Gauss distribution. The soot yield increases as the pressure or fuel
      concentration increases. The maximum of soot yield was as high as 55%. The peak
      temperature of soot yield was not changed dramatically with the pressure.
      However, it changed from 1 852 to 1 921 K as the concentration of toluene
      increase from 0.25% to 0.5%. Moreover, we compared the soot yield between toluene
      and methylcyclohexane at pressure of 4 atm with fuel concertation of 0.5%. During
      the pyrolysis of methylcyclohexane, the peak temperature of soot yield was 2 045
      K, which is about 135 K higher than that of toluene. However, the maximum soot
      yield of methylcyclohexane is only 1/8 of toluene. This work provides
      experimental reference for the research of soot particle emission in the engines
      and the mechanism of soot formation.

PMID- 30198252
TI  - Method for the in situ Measurement of pH and Alteration Extent for
      Aluminoborosilicate Glasses Using Raman Spectroscopy.
AB  - Characterization of long-term processes occurring during alteration of
      aluminoborosilicate glasses is relevant for natural as well as man-made
      materials. Static dissolution tests are a common setup for such studies, but the
      obtained results and related errors are impacted by the frequency and protocol of
      samplings performed to determine release via solution analysis, e.g., ICP-OES. A
      noninvasive method was developed to continuously monitor glass alteration based
      on in situ Raman spectrometry of the solution contained in the alteration vessel.
      The alteration of a benchmark glass, the environment assessment (EA) glass, for 7
      days at 90  degrees C showed that the pH and boron concentration results obtained
      from solution monitoring and ICP-OES quantification were similar to the pH and
      boron results obtained from chemometric modeling of the Raman spectra and within
      error of previously published results in similar conditions. The errors on
      altered amounts of glass based on B release were similar for both in situ Raman
      and ICP-OES. The new Raman method provides a more detailed picture of real time
      monitoring of an alteration experiment, with intervals between monitoring times
      as short as dozens of seconds. The in situ Raman method also helps to reduce
      perturbation to experiments caused by the physical sampling of aliquots
      (including temperature excursions, re-equilibration with atmosphere, volume
      variation, and potential chemical contamination) by limiting their number and
      frequency.

PMID- 30198253
TI  - Liquid Crystal-Templated Synthesis of Mesoporous Membranes with Predetermined
      Pore Alignment.
AB  - We demonstrate that polymeric films templated from liquid crystals (LCs) provide
      basic design principles for the synthesis of mesoporous films with predetermined
      pore alignment. Specifically, we used LC mixtures of reactive [4-(3
      acryloyoxypropyloxy) benzoic acid 2-methyl-1,4-phenylene ester (RM257)] and
      nonreactive [4-cyano-4'-pentylbiphenyl (5CB)] mesogens confined in film
      geometries. The LC alignment was maintained by functionalization of the surfaces
      contacting the films during polymerization. Through photopolymerization followed
      by extraction of the unreacted mesogens, films of area in the order of 10 cm2
      were obtained. We found that, when restricted to an area either through a
      mechanical or a configurational constraint, open and accessible pores were
      incorporated into the films. The average direction of the pores could be
      determined by the LC director during polymerization, and the average diameter of
      the pores can be tuned in the range of 10-40 nm by varying the reactive monomer
      concentration. The polymeric films synthesized here can potentially be used for
      the ultrafiltration purposes. We demonstrated successful separations of proteins
      and nanoparticles from aqueous media using the polymeric films. The films
      exhibited 2 orders of magnitude higher flux when the pores were aligned parallel
      to the permeate direction compared to the perpendicular direction. Overall, the
      outcomes of this study provide basic tools for the synthesis of porous polymeric
      films with predetermined pore directions that can potentially be suitable for
      separations, drug delivery, catalysts, and so forth.

PMID- 30198254
TI  - Au-TiO2-Loaded Cubic g-C3N4 Nanohybrids for Photocatalytic and Volatile Organic
      Amine Sensing Applications.
AB  - A green and efficient approach for efficient nanohybrid photocatalysts in
      extending the light response to the visible spectrum is a hot research topic in
      sustainable energy technologies. In this work, novel Au-TiO2@m-CN nanocomposite
      was synthesized using hard template of cubic ordered mesoporous KIT-6 via the
      nanocasting process. The as-prepared Au-TiO2@m-CN nanohybrids exhibit enhanced
      photocatalytic activities with improved stability and reusability using methyl
      orange dye. The enhanced photocatalytic performance is a result of the conjugated
      effect of catalytic active Au and TiO2 nanoparticles supported on highly
      efficient visible light sensitizer, graphitic carbon nitride (m-CN or g-C3N4),
      and ordered mesoporous morphology. Besides, the sensing performance of Au-TiO2@m
      CN nanohybrids was also tested for the detection of amine gases, wherein a
      significant response was reported for triethylamine at low operating
      temperatures. This study reveals a simple and scalable methodology to design and
      develop next generation of layered mesoporous materials for multifunctional
      applications.

PMID- 30198255
TI  - Wavelength-Tunable and Highly Stable Perovskite-Quantum-Dot-Doped Lasers with
      Liquid Crystal Lasing Cavities.
AB  - This study applies a low-cost solvothermal method to synthesize all-inorganic
      (lead-free cesium tin halide) perovskite quantum dots (AIPQDs) and to fabricate
      AIPQD-doped lasers with cholesteric liquid crystal (CLC) lasing cavities. The
      lasers present highly qualified lasing features of low threshold (150 nJ/pulse)
      and narrow line width (0.20 nm) that are attributed to the conjunction of the
      suppression of photoluminescence (PL) loss caused by the quantum confinement of
      AIPQDs and the amplification of PL caused by the band-edge effect of the CLC
      distributed feedback resonator. In addition, the lasers possess highly flexible
      lasing-wavelength tuning features and a long-term stability under storage at room
      temperature and under high humidity given the protective role of CLC. These
      advantages are difficult to confer to typical light-emitting perovskite devices.
      Given these merits, the AIPQD-doped CLC laser device has considerable potential
      applications in optoelectronic and photonic devices, including lighting,
      displays, and lasers.

PMID- 30198257
TI  - Endogenizing Capital in MRIO Models: The Implications for Consumption-Based
      Accounting.
AB  - Nearly 30% of global greenhouse gas emissions are associated with the production
      of capital goods. Consumption-based emission calculations based on multiregional
      input-output (MRIO) models allocate emissions occurring in the production of
      intermediate goods to the final goods produced in an economy. Like intermediate
      goods, capital goods are used in production processes; yet the emissions
      associated with their production are not allocated to the industries using them.
      As a result, the carbon footprint of final consumption as well as emissions
      embodied in trade are currently underestimated. Here, we address this problem by
      endogenizing capital transactions in the EXIOBASE global MRIO database, thereby
      allocating emissions from capital goods to final consumption. We find that
      endogenizing capital substantially increases the carbon footprint of final
      consumption (by up to 57% for some countries), and that the gap between
      production-based and consumption-based emissions increases for most countries. We
      also find that the global emissions embodied in trade increase by up to 11%, and
      that current patterns of bilaterally traded emissions are amplified. Furthermore,
      endogenizing capital leads to a 3-fold increase in the carbon footprint of
      certain product categories. The results suggest that our approach constitutes an
      important improvement to current input-output methodology.

PMID- 30198256
TI  - Synthesis and Luminescence Properties of Bi3+-Activated K2MgGeO4: A Promising
      High-Brightness Orange-Emitting Phosphor for WLEDs Conversion.
AB  - In this article we synthesized a series of phosphors K2MgGeO4:Bi3+ with high
      brightness for white light-emitting diodes (WLEDs) conversion and investigated
      their crystal structures and luminescence properties using powder X-ray
      diffraction, diffuse reflectance spectra, X-ray photoelectron spectroscopy,
      photoluminescence spectra, and absolute quantum efficiency. K2MgGeO4:Bi3+
      phosphor exhibits intense absorption in near-UV area and presents a broad
      asymmetric emission band with the main peak located at 614 nm, which was ascribed
      to the 3P1 -> 1S0 transition of Bi3+. The absolute quantum efficiency of the
      K2MgGeO4:0.01Bi3+ phosphor was measured to be 66.6%. Also, this orange emission
      with color chromaticity coordinates of (0.4989, 0.4400) has an excellent
      resistance to thermal quenching: its integrated intensity at 393 K still
      maintained ~85% of the one at room temperature. The WLEDs devices with Ra = 93.8
      were fabricated by employing K2MgGeO4:0.01Bi3+ as an orange phosphor, which
      contains abundant red light component in its emission spectrum. The excellent
      luminescent performance of K2MgGeO4:0.01Bi3+ suggests that it is a promising
      orange-emitting phosphor for near-ultraviolet WLEDs.

PMID- 30198258
TI  - Next Generation Sequencing Analysis of Total Small Noncoding RNAs from Low Input
      RNA from Dried Blood Sampling.
AB  - Circulating miRNAs are favored for biomarker candidates as they can reflect
      tissue specific miRNA dysregulation in disease contexts. Moreover, they have the
      additional advantage that they can be monitored in a minimally invasive manner.
      Blood-borne miRNAs are therefore currently characterized to identify, describe,
      and validate their potential suitability as biomarkers; however, sampling and as
      well miRNA detection methods limit these studies in terms of sensitivity but also
      practicability in clinical, at-home, or low-resource sampling of high-quality
      circulating RNA samples. We describe here a novel and innovative method of
      circulating RNA microsampling from minimal volume dried blood samples with direct
      enrichment for small RNA fractions in combination with ligation free library
      preparation. We evaluated crucial parameters for efficient library preparation
      from low RNA inputs of 50 pg for efficient dissection not only of miRNAs but also
      isomiRs, piRNAs, and lincRNAs. We compared these data to classical microarrays
      and characterize the technical reproducibility and its sensitivity. We
      demonstrate and evaluate a method for easy low resource sampling and NGS analysis
      of circulating RNAs providing a powerful tool for massive cohort and remote
      patient monitoring.

PMID- 30198259
TI  - Charge Transfer, Local Structure, and the Inductive Effect in Rare-Earth-Doped
      Inorganic Solids.
AB  - The charge transfer (CT) process is widely present in inorganic compounds.
      However, the explanation of this process accounting the inductive effect was not
      reported. In this work, through the analysis of local structure about the second
      nearest cations (SNCs) in some compounds doped with trivalent lanthanide, we
      verify successfully the important role of the inductive effect in the CT process.
      By introducing electronegativity factor ? ichi i( Ai)/ N - x( M), and ionic
      radius factor ? i ri( Ai)/ N, the semiquantitative model is proposed. Strong
      positive correlation between the electronegativity factor and CT energy and
      strong negative correlation between the ionic radius factor and CT energy are
      given. At last, the interrelationship among these two inductive factors, the CT
      process, the change of local coordination structure, and the chemical composition
      is revealed. This work will facilitate our understanding of the CT process and
      the delicate role of the local structure and the inductive effect.

PMID- 30198260
TI  - Embedding a Ruthenium-Based Structural Mimic of the [Fe]-Hydrogenase Cofactor
      into Papain.
AB  - We describe the synthesis of the ruthenacyclic carbamoyl complexes [Ru(2
      NHC(O)C5H3NMe)(CO)2( o,o-Me2-C6H3S)(L)] (L = H2O or MeCN), which have a labile
      water or acetonitrile ligand at their sixth coordination sites. Steric bulk
      around the ruthenium center is essential in preventing isomerization and
      dimerization, and embedding within papain can be achieved via coordination of its
      sole free cysteine residue. The observed chemistry parallels that of the natural
      [Fe]-hydrogenase.

PMID- 30198261
TI  - Herbivore-Diet Analysis Based on Illumina MiSeq Sequencing: The Potential Use of
      an ITS2-Barcoding Approach to Establish Qualitative and Quantitative Predictions
      of Diet Composition of Mongolian Sheep.
AB  - DNA-barcoding approaches to estimate the diet compositions of grazing animals
      have received significant attention, and particularly when combined with next
      generation sequencing, these techniques have substantially improved in recent
      years. In this study, the identity and species composition of plant material
      ingested by Mongolian sheep were estimated through the use of 350 bp ITS2 gene
      sequences of the vegetation found in fecal samples. Four diets were formulated
      using varying amounts of eight plant species that are common in the grasslands of
      northern China. Sixteen Mongolian sheep were taken from pastures and randomly
      assigned to four groups, and each group received one of four diets. Each sheep
      was randomly assigned to one of 16 confinement pens and fed its respective diet
      for 12 consecutive days. Fecal samples were removed from each pen from days 7-12,
      preserved, and composited for each pen. All herbage species included in the daily
      diets were detected in each fecal sample, with the exception of Phragmites
      australis. Moreover, 12 additional different plant species were retrieved from
      feces of the experimental sheep. The obtained data provided preliminary support
      for the use of the ITS2 barcode to determine which plants were consumed.
      Moreover, the proportions of the herbage DNA sequences recovered from sheep feces
      and those of the herbage masses in the daily diets did not completely match.
      These results indicate that the non-Gramineae DNA sequences amplified with ITS2
      primers (including those of Chenopodium album, Artemisia scoparia, Artemisia
      tanacetifolia, and Medicago sativa) far exceeded those of the Gramineae species
      (including Leymus chinensis and Puccinellia distans), which constitute the
      largest share of the experimental diets. A significant positive correlation
      (Spearman's rho = 0.376, P = 0.003) between the actual herbage mass proportions
      in the experimental diets and the herbage-DNA-sequence proportions provided
      sufficiently favorable support for the further investigation of DNA barcoding for
      the quantification of plants in feces. A significant regression coefficient was
      found between the relative DNA-sequence proportions of L. chinensis ( R2 = 0.82,
      P < 0.0001), P. distans ( R2 = 0.64, P = 0.0017), and C. album ( R2 = 0.98, P <
      0.0001) and their respective herbage mass proportions. The quantitative
      relationship can be expressed by the linear-regression equations y = 0.90 x -
      0.22, y = 0.98 x - 0.03, and y = 5.00 x - 0.25, respectively. Thus, these results
      demonstrate that dietary-DNA-barcoding methods exhibited potential in providing
      valuable quantitative information regarding food-item components. However, it
      should be noted that this explorative data needs to be further improved by using
      additional genes and by creating a sophisticated reference database, thus
      enhancing both quality and accuracy of the obtained results.

PMID- 30198262
TI  - Ga3+ Doping Induced Simultaneous Size/Shape Control, Enhanced Red Upconversion
      Luminescence, and Improved X-ray Imaging of ZnO:Yb/Tm for Multifunctional
      Nanoprobes.
AB  - We report that the efficient Ga3+-doped ZnO:Yb/Tm (7/0.5 mol %) upconversion
      nanoparticles (UCNPs) can simultaneously control size/shape and enhance red
      upconversion luminescence (UCL) by transition-metal Ga3+ doping. The dynamic
      decay time reveals that the intensity of red upconversion luminescence increases
      with increasing Ga3+ content. Furthermore, upconversion nanoparticles are
      fabricated through silica layer with Stober method. The lung of mouse with the
      ZnO:Ga/Yb/Tm@SiO2 injection can be readily visualized using X-ray imaging, which
      will influence the field of biological probe based on UCNPs@SiO2.

PMID- 30198263
TI  - Effect of Malt-Derived Potential Antioxidants on Dimethyl Sulfide Oxidation.
AB  - During malt kilning, dimethyl sulfide (DMS) is partly oxidized to dimethyl
      sulfoxide (DMSO), which can be reduced by yeast to generate DMS during
      fermentation. The aim of this study was to test the effect of malt-derived
      potential antioxidants on DMS oxidation and to assess their applicability for
      DMSO minimization. In the presence of 18 MUM copper, all tested antioxidants (250
      MUM) catalyzed DMS oxidation to deviating extents (sulfite > ascorbic acid (Asco)
      > gallic acid (GA) > L-cysteine (Cys) > L-glutathione (GSH)). Hydrogen peroxide
      was found as primary DMS oxidant for each substance except for sulfite. Electron
      spin resonance spectroscopy provided evidence for the formation of bisulfite
      radicals and peroxymonosulfate radicals, which are proposed as being capable of
      exhaustive DMS oxidation (~100%) over a wide concentration. The data demonstrate
      that use of antioxidants per se cannot be suggested for the minimization of DMSO
      formation in malt and other foodstuffs. Potential shifts from pro- to
      antioxidative behavior of antioxidants and their implications on malt quality are
      discussed.

PMID- 30198264
TI  - Synthesis of CF3CH2-Containing Indolines by Transition-Metal-Free
      Aryltrifluoromethylation of Unactivated Alkenes.
AB  - With an unactivated double bond as the radical acceptor, allyl amines underwent a
      metal-free trifluoromethylation/cyclization cascade with CF3SO2Na (Langlois'
      reagent), affording CF3CH2-containing indolines and tetrahydroisoquinolines,
      whose practical syntheses are significant challenges. This protocol features mild
      conditions, low cost, and a broad substrate scope.

PMID- 30198265
TI  - Conducting Anilate-Based Mixed-Valence Fe(II)Fe(III) Coordination Polymer: Small
      Polaron Hopping Model for Oxalate-Type Fe(II)Fe(III) 2D Networks.
AB  - The mixed-valence FeIIFeIII 2D coordination polymer formulated as
      [TAG][FeIIFeIII(ClCNAn)3].(solvate) 1 (TAG = tris(amino)-guanidinium, ClCNAn2- =
      chlorocyanoanilate dianionic ligand) crystallized in the polar trigonal space
      group P3. In the solid-state structure, determined both at 150 and at 10 K,
      anionic 2D honeycomb layers [FeIIFeIII(ClCNAn)3]- establish in the ab plane, with
      an intralayer metal-metal distance of 7.860 A, alternating with cationic layers
      of TAG. The similar Fe-O distances suggest electron delocalization and an average
      oxidation state of +2.5 for each Fe center. The cation imposes its C3 symmetry to
      the structure and engages in intermolecular N-H...Cl hydrogen bonding with the
      ligand. Magnetic susceptibility characterization indicates magnetic ordering
      below 4 K and the presence of a hysteresis loop at 2 K with a coercive field of
      60 Oe. Mossbauer measurements are in agreement with the existence of Fe(+2.5)
      ions at RT and statistic charge localization at 10 K. The compound shows
      semiconducting behavior with the in-plane conductivity of 2 * 10-3 S/cm, 3 orders
      of magnitude higher than the perpendicular one. A small-polaron hopping model has
      been applied to a series of oxalate-type FeIIFeIII 2D coordination polymers,
      providing a clear explanation on the much higher conductivity of the anilate
      based systems than the oxalate ones.

PMID- 30198266
TI  - Effects of Decavanadate Salts with Organic and Inorganic Cations on Escherichia
      coli, Giardia intestinalis, and Vero Cells.
AB  - Decavanadate salts with nicotinamide (3-pyridinecarboxamide, 3-pca) and
      isonicotinamide (4-pyridinecarboxamide, 4-pca) in both neutral and protonated
      forms, (3-Hpca)4[H2V10O28].2H2O.2(3-pca) (complex I) and (4-Hpca)4[H2V10O28].2(4
      pca) (complex II), have been synthesized and characterized by vibrational
      spectroscopy (infrared and Raman), thermogravimetric analysis (TGA), 51V NMR, and
      single-crystal X-ray diffraction analysis. The effects of sodium decavanadate
      (henceforth called NaV10) and compounds I and II on Escherichia coli, Giardia
      intestinalis, and Vero (African green monkey epithelial kidney) cells were
      evaluated. Enhanced growth inhibitory activity against E. coli cultures was
      observed upon treatment with products I and II when compared to that with NaV10
      (GI50 values of 2.8, 4.0, and 11 mmol L-1, respectively), as well as lower cell
      viability as measured by the intake of propidium iodide (PI). Exposure of Giardia
      trophozoites to NaV10 and II revealed reduction in trophozoite viability (GI50
      values of ca. 10 MUmol L-1) and affected the parasite adherence to both
      polystyrene culture tubes and a monolayer of Vero cells, even at low
      concentrations. A lesser effect on Giardia was shown for I. Furthermore, all
      three compounds were significantly less toxic to Vero cells than the reference
      drug, albendazole, employed in the treatment of giardiasis. Toxicity reports of
      oxidovanadium compounds toward Giardia are unprecedented and open a path to the
      development of new therapeutic agents.

PMID- 30198267
TI  - Droop-Free Colloidal Quantum Dot Light-Emitting Diodes.
AB  - Colloidal semiconductor quantum dots (QDs) are a highly promising materials
      platform for implementing solution-processable light-emitting diodes (LEDs). They
      combine high photostability of traditional inorganic semiconductors with chemical
      flexibility of molecular systems, which makes them well-suited for large-area
      applications such as television screens, solid-state lighting, and outdoor
      signage. Additional beneficial features include size-controlled emission
      wavelengths, narrow bandwidths, and nearly perfect emission efficiencies. State
      of-the-art QD-LEDs exhibit high internal quantum efficiencies approaching unity.
      However, these peak values are observed only at low current densities ( J) and
      correspondingly low brightnesses, whereas at higher J, the efficiency usually
      exhibits a quick roll-off. This efficiency droop limits achievable brightness
      levels and decreases device longevity due to excessive heat generation. Here, we
      demonstrate QD-LEDs operating with high internal efficiencies (up to 70%)
      virtually droop-free up to unprecedented brightness of >100,000 cd m-2 (at ~500
      mA cm-2). This exceptional performance is derived from specially engineered QDs
      that feature a compositionally graded interlayer and a final barrier layer. This
      QD design allows for improved balance between electron and hole injections
      combined with considerably suppressed Auger recombination, which helps mitigate
      efficiency losses due to charge imbalance at high currents. These results
      indicate a significant potential of newly developed QDs as enablers of future
      ultrabright, highly efficient devices for both indoor and outdoor applications.

PMID- 30198268
TI  - Stable Air Nanobubbles in Water: the Importance of Organic Contaminants.
AB  - Nanobubbles, surprisingly stable submicrometer gas bubbles in water, appear to be
      common in water and biological fluids and are of great interest in technical
      applications ranging from ultrasound contrast agents to flotation in the mining
      industry. Nanobubbles on surfaces have been more researched than freely floating
      bulk nanobubbles, and the reason for their stability appears to be better
      explained. The stability of bulk nanobubbles is less well explained, several
      theories exist, and even their existence is sometimes questioned. In the present
      study, an attempt was made to generate nanobubbles through hydrodynamic
      cavitation as well as through vigorous shaking in test tubes, and it was found
      that none of these methods generated a detectable concentration of possible bulk
      nanobubbles if pure water was used, with or without a small addition of NaCl, the
      equipment was cleaned properly, and certain plastic materials were avoided. These
      results indicate that trace organic contaminants are necessary for nanobubble
      stabilization. Experiments were also made with the dissolution of a high
      concentration of inorganic salts, which generated bubbles by creating air
      supersaturation. Light scattering submicron particles were found in all solutions
      and appeared to be actual gas bubbles in at least one case. However, in many
      cases, these light scattering particles were unaffected by vacuum and pressure
      and appear, therefore, to be something else other than air bubbles. It is
      concluded that, in future research on nanobubble stability, it is very important
      to avoid contamination, as well as to ascertain that light scattering objects
      really are bubbles and not oil droplets or particles.

PMID- 30198269
TI  - Intramolecular Transamidation of Secondary Amides via Visible-Light-Induced
      Tandem Reaction.
AB  - Transformation of secondary amides to N-acylimines was used as an effective
      strategy to activate otherwise unreactive amide bonds. In this tandem reaction,
      the Rose Bengal-catalyzed photo-oxidative coupling of arylglycine esters and
      enamides generates N-acylimines, which undergo intramolecular transamidation and
      imine hydrolysis to afford bioactive acyl Mannich base derivatives under metal
      free and mild conditions.

PMID- 30198270
TI  - [200th birth anniversary of Ignatius Philipp Semmelweis].
AB  - Ignaz Phillip Semmelweis's significance for the history of medicine lies in his
      discovery of the cause of puerperal fever. He discovered it during his work at
      the First Obstetrics Clinic of the Vienna's Allgemeines Krankenhaus. Since the
      mentioned Clinic, led by the doctors, had much higher mortality rates of the
      child-bearing women than the Second Obstetrics Clinic, led by the midwives, he
      wanted to determine the causes of such a state. He came to the conclusion that
      puerperal sepsis was transmitted by the doctors and medical students, who after
      performing the anatomical sections started to perform the births with their hands
      beforehand washed only with soap. Semmelweis instead proposed a mandatory hand
      washing in a potassium-hypochlorite solution thus making the mortality at the
      First equivalent to the mortality at the Second Obstetrics Clinic. Despite this,
      his discovery was rejected by the established medical circuits.

PMID- 30198271
TI  - Francisco Arceo de Fregenal and the treatment of clubfoot up to the sixteenth
      century.
AB  - The correction of clubfoot as a subject of study is somewhat unusual, especially
      if one considers that up until the Renaissance only two authors dealt with the
      subject of this inherited disorder. On the one hand is Ambroise Pare, whose
      contributions to traumatology and orthopaedics are staggering, and on the other,
      Francisco Arceo de Fregenal, also known as the Ambroise Pare of Spain. Both men
      developed a method for treating this condition, and a special orthopaedic shoe.
      So, why is it that in the Spanish literature the French surgeon was considered
      the pioneer in the development of an orthopaedic boot from the start and not
      Arceo? Why was the work of the Spaniard not studied in depth, as it deserves to
      be? These questions troubled us and led us to write this paper, in which as the
      primary objective we decided to highlight Arceo's contributions to the field of
      orthopaedics. Concrete arguments and works exist today that have led to common
      agreement among scholars of the subject that the Spanish surgeon was a Jewish
      convert. The social, economic and political conditions in Europe at that time may
      give us some idea of the difficulties for a Jewish convert in the sixteenth
      century, and clearly, it was difficult for a scientist to have followers who
      would defend his methods and technical ideas. Nevertheless, we believe that
      Francisco Arceo de Fregenal deserves more recognition and his work should
      continue to be studied in more depth.

PMID- 30198272
TI  - [Father and sons: Feller family members in the context of the beginnings of
      advertising in Croatia].
AB  - This paper presents the role of Eugen Viktor Feller, a pharmacist and factory
      owner, with an emphasis on his marketing strategy in advertising his pharmacy
      specialty Elsa. Various types of contemporary press and advertising leaflets and
      packaging were used as a starting point for analysis. The abundance of the
      collected material provided an insight into Feller's communication strategy of
      the approach to consumers, comparing advertising in different media and time
      spans. Following the appearance and elaboration of visual communication phenomena
      as part of family interest, approaches and advances in the development of
      advertising in the projects of Feller's sons Miroslav and Ferdinand were
      presented. Upgrading to the father's positive marketing experience they begin a
      more contemplative advertising campaign. Ferdinand Feller introduces the concept
      of collective pharmaceutical propaganda into pharmaceutical marketing, while
      Miroslav Feller becomes one of the leaders in the development of
      institutionalization and professionalization of commercial graphic design. Thus,
      marketing development was demonstrated through marketing approaches and
      innovative ideas of the three members of Feller family, illustrating the shift in
      approaches that marked the beginning of a different management within an
      industrial society, where advertising became an indispensable part and a promoter
      of market relationships.

PMID- 30198273
TI  - Public health experiences from interwar Croatia (Yugoslavia) and making western
      medicine in the 1930s China.
AB  - To gain control and domination over a particular territory, medicine was often
      used as a tool for promoting different interests. Using the activities of the
      League of Nations Health Organization and the Rockefeller Foundation on the
      territory of China in 1930s, this paper analyses the interconnection of the
      international and local factors in the transformation of the traditional Chinese
      milieu to suit the new and trendy public health projects. These activities were
      conducted not only to improve the public health conditions in the country, but
      also to introduce the Chinese public health to the processes of
      internationalization and standardization to the west oriented type of medicine
      and medical education. Initiated processes necessarily interfered with the
      political influences, economical interests and cultural environment as well as
      with military actions in this very turbulent time of Chinese history. Public
      health activities were carried out by the group of international experts. Among
      them the main position took two Croatian physicians: Andrija Stampar (one of the
      founders of the World Health Organisation later) and Berislav Borcic (a director
      of the School of Public Health in Zagreb). On the basis of correspondence between
      these two physicians, as well as the travel diary of Andrija Stampar, this essay
      presents some less known details about the situation in China and the interlacing
      between politics and medicine.

PMID- 30198274
TI  - Pheidias Apollonius (ca. 4th century BC), unveiling the ancient Greek medico
      philosophical school of the island of Rhodes.
AB  - The ancient Greek medico-philosophical school of the island of Rhodes was lost in
      the fog of history. However, the discovery of a stone column dedicated to
      Pheidias unveiled somehow some parts of its tale. The Island of Rhodes became in
      the 4th century BC a place of significant process in philosophy and medicine.
      Having both an Asclepieion and a Medical School with a rich library, the Rhodian
      Asclepiades transmitted their knowledge to future schools. Pheidias Apollonius
      was a member of the School of Rhodes, who was celebrated for his practise by the
      city-state of Athens. His magnitude testified in a way the supremacy of the
      school that he originated from.

PMID- 30198275
TI  - The concept of portal system obstruction in Avicenna's canon of medicine.
AB  - Historical literature on portal hypertension is mainly focused on the
      contemporary advances in therapeutic methods, especially surgical ones. However,
      it seems that the origin of the human knowledge on the portal system, its
      association with the caval system, obstructive pathologies in this system and the
      gastrointestinal bleeding due to hepatic diseases might be much older than
      previously believed. Avicenna provided a detailed anatomy of the portal venous
      system and its feeding branches in the Canon of Medicine. Soddat al-Kabed va al
      Masarigha (liver and mesenteric occlusion) is also a disease presented by
      Avicenna with clinical, etiological and therapeutic descriptions suggesting the
      fact that Soddat al-Kabed va al-Masarigha has multiple similarities with the
      currently identified concept of "portal hypertension". He presented sense of
      heaviness in the liver area with or without mild pain, anemia, pale and
      inappropriate body color, and loose stool which can be complicated with ascites,
      infection, fever and abdominal pain as clinical manifestations of this disease.
      He has also suggested therapeutic approaches including laxative and diuretic
      herbs to help excreting the obstructive material into stool or urine.

PMID- 30198276
TI  - Tapping on the chest of history. Lost and found memories of Leopold Auenbrugger,
      inventor of percussion, in Austria and beyond.
AB  - Leopold Auenbrugger (1722-1809), the inventor of percussion, joins Rene Laennec
      as the father of modern physical examination. On the occasion of the bicentennial
      of the invention of the stethoscope (1816), I went in search of the material
      footprints left by Auenbrugger in his homeland, Austria. This attempt led me to
      construct a rather fragmented picture, with some disillusionment (e.g. about his
      tomb) and some pleasant surprise (e.g. a new interpretation of the extant
      iconography). Apparently, posterity has not been sufficiently mindful of or
      grateful towards this great innovator of medical science. All the more reason for
      knowing and protecting what is left of him: buildings, monuments, portraits...
      Anyway, Leopold Auenbrugger is honored and implicitly remembered today, as he was
      in the past, every time a doctor practices the percussion on the chest of a
      patient (i.e. billions of times each year).

PMID- 30198277
TI  - [A comparison between Giovan Battista Rini and Paolo Gorini].
AB  - This short paper aims to explore analogies between the two famous embalmers from
      Lombardy, Giovan Battista Rini and Paolo Gorini. These extraordinary figures are
      wellknown due to their petrified specimens and are compared on the basis of
      preparation typologies, materials employed and the shroud of mystery that
      characterized their stories.

PMID- 30198278
TI  - Innovative use of magnesium oxide in the treatment of "neuralgia of the celiac
      plexus of rheumatic origin" by G. Moscati in 1923.
AB  - We presented and discussed one interesting medical prescription by doctor
      Giuseppe Moscati (1880-1927), who prescribed magnesium oxide (magnesia usta) to a
      patient with the diagnosis of "neuralgia of the celiac plexus of rheumatic
      origin". Besides the traditional use of magnesium as antacid remedy at the time,
      we raised the hypothesis that magnesium could be administered by Moscati in order
      to treat the neuralgia itself. Considering the scientific background of Moscati
      at the school of Filippo Bottazzi (1867-1941), a father of Italian biochemistry,
      we suggested that the doctor tried to apply the preliminary concepts acquired
      from electrophysiological studies on magnesium to his clinical practice. Only
      after decades, magnesium was recognized a fundamental ion in the energy
      metabolism and in contributing to maintain the ionic intracellular homeostasis,
      including for neurons.

PMID- 30198280
TI  - Immunogenicity of a plasmid DNA vaccine encoding G1 epitope of bovine ephemeral
      fever virus G glycoprotein in mice.
AB  - The aim of this study was to investigate the immunogenicity of a plasmid
      deoxyribonucleic acid (DNA) vaccine encoding the G1 epitope of bovine ephemeral
      fever virus (BEFV) G glycoprotein in mice. A plasmid DNA carrying the G1 gene was
      constructed and designated as pcDNA3.1-G1. The expression of the target gene was
      confirmed in human embryonic kidney 293 (HEK 293) cells transfected with pcDNA3.1
      G1 by indirect immunofluorescent staining. Immunisation experiments were
      intramuscularly carried out by vaccinating 6-week-old female mice in four groups,
      including the pcDNA3.1-G1 construct, pcDNA3.1 (+) plasmid alone, BEF-inactivated
      vaccine and phosphate-buffered saline (PBS) (1X) three times with 2-week
      intervals. Fourteen days after the last immunisation, the animals were bled and
      the resulting sera were tested for anti-G1-specific antibodies by immunoblotting
      analysis, indirect enzyme-linked immunosorbent assay (ELISA) and virus
      neutralisation (VN) test. Serological assays showed that the pcDNA3.1-G1
      construct expressing G1 protein was able to elicit specific antibodies against
      this antigen. Virus neutralisation test showed that pcDNA3.1-G1 could induce anti
      BEFV-neutralising antibodies in mice. Our findings indicated that a new dimension
      can be added to vaccine studies for bovine ephemeral fever (BEF) using eukaryotic
      expression plasmids encoding the G1 antigen in the future.

PMID- 30198279
TI  - Spatial and temporal distribution of foot-and-mouth disease in four districts
      situated along the Uganda-Tanzania border: Implications for cross-border efforts
      in disease control.
AB  - Foot-and-mouth disease (FMD) is one of the major trans-boundary animal diseases
      in East Africa causing economic loss to farmers and other stakeholders in the
      livestock industry. Foot-and-mouth disease occurs widely in both Uganda and
      Tanzania with annual outbreaks recorded. With the recent introduction of the
      Progressive Control Pathway for FMD control (PCP-FMD) in eastern Africa,
      knowledge of the spatial and temporal distribution of FMD at the border area
      between Uganda and Tanzania is helpful in framing engagement with the initial
      stages of the PCP. Retrospective data collected between 2011 and 2016 from four
      districts located along the border areas of Uganda and Tanzania, recorded 23 and
      59 FMD outbreaks, respectively, for the entire study period. Analysis showed that
      46% of the 82 recorded outbreaks occurred in 20% of sub-counties and wards
      immediately neighbouring the Uganda-Tanzania border and 69.5% of the outbreaks
      occurred during the dry months. While the serotypes of the FMD virus responsible
      for most outbreaks reported in this region were not known, previous research
      reported South African Territory (SAT) 1, SAT 2 and O to be the serotypes in
      circulation. The results from this study provide evidence of the endemic status
      of FMD on the Uganda-Tanzania border and emphasise that the border area should be
      given due consideration during FMD control drives and that cross-border
      coordination should be prioritised. With the limited data on circulating
      serotypes in this area, there is a need for more vigilance on FMD case detection,
      laboratory diagnostic confirmation and provision of more complete documentation
      of outbreaks. This work further recommends more studies on cross-border livestock
      movement coupled with phylogenetics in order to understand the spread of the FMD
      in the border area.

PMID- 30198281
TI  - Lay perceptions, beliefs and practices linked to the persistence of anthrax
      outbreaks in cattle in the Western Province of Zambia.
AB  - Anthrax, a neglected zoonotic disease that is transmitted by a spore-forming, rod
      shaped bacterium, Bacillus anthracis, has reached endemic proportions in the
      Western Province of Zambia. Transmission of anthrax from the environment as well
      as between cattle has been observed to be partly because of entrenched beliefs,
      perceptions and traditional practices among cattle farmers in the known outbreak
      areas. This study was aimed at exploring lay perceptions, beliefs and practices
      that influence anthrax transmission in cattle of the Western Province. A mixed
      methods study was conducted from August to December 2015. Quantitative data were
      collected using a cross-sectional survey. Qualitative data were generated by
      interviewing professional staff and community members. Five focus group
      discussions and five key informant interviews were conducted. Thematic analysis
      of interview data was performed using NVivo software. The findings suggested that
      cattle anthrax was biologically as well as culturally maintained. Cattle farmers
      were reluctant to have their livestock vaccinated against anthrax because of
      perceived low efficacy of the vaccine. Also, the cattle farmers did not trust
      professional staff and their technical interventions. Popular cultural practices
      that involved exchange of animals between herds contributed to uncontrolled
      cattle movements between herds and subsequent transmission of anthrax. These
      findings imply the need for professional staff to be culturally competent in
      handling socio-cultural issues that are known to be barriers for disease control
      in animals. There is a need to develop a policy framework that will foster
      integrated control of anthrax across disciplines.

PMID- 30198282
TI  - First record of the marine turtle leech (Ozobranchus margoi) on hawksbill turtles
      (Eretmochelys imbricata) in the inner granitic Seychelles.
AB  - Ozobranchus spp. are leeches that feed solely on turtle blood. They are common
      ectoparasites found on a range of marine turtle species, with some species of the
      leech being implicated as vectors of fibropapilloma-associated turtle herpesvirus
      (FPTHV). Green (Chelonia mydas) and hawksbill (Eretmochelys imbricata) turtles
      are the two commonly occurring species in the inner granitic islands of the
      Seychelles. Routine monitoring of nesting turtles on Cousine Island, Seychelles,
      allowed for opportunistic sightings of leeches on two hawksbill females. In both
      cases infestation was low, with three leeches collected off one female turtle and
      five off the other. No obvious signs of papillomas secondary to infection of
      FPTHV were seen. All of the turtle leeches collected were determined to be
      Ozobranchus margoi as they had five pairs of lateral digiform branchiae. The
      specimens were deposited in the Seychelles Natural History Museum on Mahe. To the
      best of our knowledge this is the first record of Ozobranchus margoi recorded in
      the inner granitic Seychelles on hawksbill turtles.

PMID- 30198283
TI  - Health status of families: A comparative study of one-parent and two-parent
      families in Ondo State, Nigeria.
AB  - BACKGROUND:  The family plays a central role in the provision and maintenance of
      health status of its members and all factors that contribute to achieving optimal
      health. Aim: To compare the health status of one-parent and two-parent families
      using the McMaster model of family functioning. Setting: Ondo State, Southwest
      Nigeria. Methods: A descriptive cross-sectional design, using multi-stage simple
      random sampling technique. Data were collected using an adopted self-administered
      questionnaire from 250 purposely selected families from each sample group. The
      data entering was analysed using Statistical Package for Social Sciences (SPSS)
      software version 17.0. Results: Findings showed that one-parent fathers scored
      higher (mean = 74.4 +/- 10.30) than two-parent fathers (70.5 +/- 13.05), while
      one-parent mothers scored higher (mean = 69.7 +/- 15.10) than two-parent mothers
      (mean 67.7 +/- 14.78). This means that one-parent fathers have a better self
      reported health status than two-parent fathers, while one-parent mothers have a
      better self-reported health status than two-parent mothers. One-parent fathers
      have the best self-reported health status. No significant (p > 0.05) difference
      in the health status of children from both families. Conclusion: Fathers are
      healthier than mothers, while one-parent fathers are healthier than two-parent
      fathers. Comparing the two groups of families, parents from one-parent families
      reported better health status than parents from two-parent families, whereas
      within each family group, fathers reported better health status than mothers.
      This places responsibility on health care professionals to explore family
      contexts during clinic visits so as to render a more comprehensive health care
      service to families.

PMID- 30198284
TI  - Factors associated with retention of community health workers in maternal,
      newborn and child health programme in Simiyu Region, Tanzania.
AB  - BACKGROUND:  Attrition of community health workers (CHWs) continues to threaten
      the full realisation and sustainability of community-based health programmes
      globally. Aim: This study aimed to understand factors associated with CHWs'
      recruitment and their retention. Setting: This study was conducted in five
      districts of the Simiyu Region, namely, Bariadi, Busega, Itilima, Maswa and Meatu
      in north-western Tanzania. Methods: In this cross-sectional study design, 341
      CHWs who were working with the maternal health programme were randomly selected.
      Semi-structured questionnaires were administered to all participants. Data were
      descriptively and inferentially analysed using SPSS version 20. Results: Majority
      (58.0%) of CHWs were below 35 years. Over half (53.1%) had completed primary
      education only. Motivation factors for being CHW were aspiration to serve the
      community and desire for further training to become a qualified medical
      practitioner. Community recognition and financial incentives were among the key
      retention reasons for the CHWs. Being married (odds ratio [OR] 5.9, 95%
      confidence interval [CI] 1.7-20.1) having prior volunteer experience (OR 10.5 95%
      CI 12.7-40.5) and prior employment OR 21.8 (CI 12.2-38.9) were positively
      associated with retention of CHWs, while being a female was negatively associated
      with retention OR 0.4 (CI 0.2-0.8). Conclusions: Both financial and non-financial
      incentives were critical in contributing to the retention of CHWs. Thus, health
      programmes should carefully select CHWs by understanding their motives
      beforehand, and provide them with incentives.

PMID- 30198285
TI  - An audit of the screen-and-treat intervention to reduce cryptococcal meningitis
      in HIV-positive patients with low CD4 count.
AB  - BACKGROUND:  HIV-associated cryptococcal meningitis (CCM) and related mortality
      may be prevented by the effective implementation of a screen-and-treat
      intervention. Aim: The aim of this study was to assess the effectiveness of the
      screen-and-treat intervention at a regional hospital in KwaZulu-Natal province,
      South Africa. Method: This was a descriptive study in which the records of
      patients seen in 2015 and 2016 with a CD4 count <= 100 cell/mm3 were retrieved
      from National Health Laboratory Service (NHLS) records and matched against
      patients admitted for HIV-associated CCM. Results: A total of 5.1% (190 out of
      3702) patients with CD4 count <= 100 cell/mm3 were cryptococcal antigen positive
      (CrAg +ve), of whom 22.6% (43 out of 190) were admitted with CCM. Patients who
      were CrAg +ve had significantly lower CD4 counts (mean CD4 = 38.9 +/- 28.5) when
      compared to CrAg -ve patients (mean CD4 = 49.9 +/- 37.4) with p = 0.0001. Only
      2.6% (5 out of 190) of patients were referred for a lumbar puncture (LP) as part
      of the screen-and-treat intervention, whilst 38 who were CrAg +ve self-presented
      with CCM. Eighty-eight patients were admitted for suspected CCM: eight because of
      the screen-and-treat-intervention (none of whom had meningitis based on
      cerebrospinal fluid results) and 80 of whom self-presented and had confirmed CCM.
      The overall mortality of patients admitted with CCM was 30% (24 out of 80).
      Conclusion: The current ad-hoc screen-and-treat intervention was ineffective in
      detecting patients at risk of developing CCM. Systems need to be put in place to
      ensure that all CrAg +ve patients have an LP to detect subclinical CCM to improve
      the outcome for those with HIV-associated CCM.

PMID- 30198286
TI  - Experiences of community caregivers in the assessment of malnutrition using mid
      upper arm circumference measurement in children under 5 years old.
AB  - BACKGROUND:  Malnutrition is a major public health challenge in developing
      countries. It has been identified as an important cause of child mortality and
      morbidity and leads to inadequate physical and cognitive development in children.
      The South African government implemented a strategy for malnutrition assessment
      in children under 5 years by community caregivers (CCGs), who would then refer
      children at risk or those having developed malnutrition to primary health care
      clinics. Irrespective of this strategy, children still present at clinics with
      severe malnutrition. AIM:  The aim of the study was to explore and describe the
      experiences of community caregivers with the assessment of malnutrition in
      children under 5 years old. SETTING:  The study was conducted in North Area six
      of eThekwini district in the province of KwaZulu-Natal. METHODS:  A qualitative,
      exploratory descriptive approach was used to collect data from 13 purposively
      selected CCGs. Content analysis was used to analyse data. RESULTS:  The majority
      of participants were dissatisfied with the training, as it was conducted in a
      language in which they were not proficient. They reported a lack of support and
      supervision in their performance such that mid-upper arm circumference was non
      prioritised. They were dissatisfied with work overload not matched by
      remuneration and they worked under unsafe conditions. CONCLUSION:  Effective
      training of CCGs needs to be conducted in the language that they understand to
      combat malnutrition in children under 5 years. CCGs have multiple roles and may
      need to prioritise their work; this is not easy and requires specific guidance
      from skilled health professionals.

PMID- 30198287
TI  - Baseline measures of primary health care team functioning and overall primary
      health care performance at Du Noon Community Health Centre.
AB  - BACKGROUND:  Research consistently demonstrates the importance of effective team
      work for improving the quality of health care. We conducted a baseline measure of
      primary health care (PHC) team effectiveness and overall PHC performance at a
      primary care facility. AIM:  To improve PHC team effectiveness and ultimately the
      quality and user experience of primary care at a community health centre (CHC).
      SETTING:  Du Noon CHC in the southern and western substructure of the Cape Town
      Metro district services (MDHS). METHODS:  A cross-sectional study using a
      combination of the Nominal Group Technique (NGT) consensus method and the South
      African Primary Care Assessment Tool (ZA PCAT) to assess PHC team effectiveness
      and PHC organisation and performance. RESULTS:  The ZA PCAT was administered to
      110 CHC users (patients) and 12 providers (doctors and clinical nurse
      practitioners). Data from 20 PHC team members showed they perceived their team as
      well functioning (70% agreement on a 7-item PHC team assessment tool incorporated
      into the ZA PCAT). The NGT method achieved participant (20) consensus on
      communication and leadership as the main challenges to effective team functioning
      and on ideas to overcome the challenges. The ZA PCAT user data showed 18.2% of
      users rated first contact access as acceptable to good; 47.3% of users rated
      ongoing care as acceptable to good. Provider data showed that 33% of providers
      rated first contact access as acceptable to good; 25% of providers rated ongoing
      care as acceptable to good. First contact access received the lowest acceptable
      to good score (18.2%) and comprehensiveness (services available) the highest
      score (88.2%) from users. For the providers, the lowest acceptable to good score
      was for ongoing care (25%) and the highest acceptable to good score was for
      primary health care team availability (100%). The ZA PCAT total primary scores
      were good (above 60%) for both users and providers but moderately higher for the
      providers. CONCLUSION:  Knowledge of how teams perceive their effectiveness can
      motivate them to generate ideas for improving performance. There were
      discrepancies between providers' assessment of team functioning using the ZA PCAT
      measure and the NGT method results. The ZA PCAT also showed differences between
      providers' and users' perceptions of PHC performance - consistent with the
      findings of the multi-CHC Western Cape ZA PCAT study. These findings should
      encourage and support CHC and district level staff in their efforts to improve
      the quality and user experience of primary care, as well as PHC team performance.

PMID- 30198288
TI  - Emergency contraceptive knowledge, attitudes and practices among female students
      at the University of Botswana: A descriptive survey.
AB  - BACKGROUND:  Unintended pregnancies are associated with unsafe abortions and
      maternal deaths, particularly in countries such as Botswana, where abortion is
      illegal. Many of these unwanted pregnancies could be avoided by using emergency
      contraception, which is widely available in Botswana. AIM:  To assess the level
      of knowledge, attitudes and practices of female students with regard to emergency
      contraception at the University of Botswana. SETTING:  Students from University
      of Botswana, Gaborone, Botswana. METHODS:  A descriptive survey among 371
      students selected from all eight faculties at the university. Data were collected
      using a self-administered questionnaire and analysed using the Statistical
      Package for Social Sciences. RESULTS:  The mean age was 20.6 years (SD 1.62), 58%
      were sexually active, 22% had used emergency contraception and 52% of pregnancies
      were unintended. Of the total respondents, 95% replied that they had heard of
      emergency contraception; however, only 53% were considered to have good
      knowledge, and 55% had negative attitudes towards its use. Students from urban
      areas had better knowledge than their rural counterparts (p = 0.020). Better
      knowledge of emergency contraception was associated with more positive attitudes
      towards actual use (p < 0.001). Older students (p < 0.001) and those in higher
      years of study (p = 0.001) were more likely to have used emergency contraception.
      CONCLUSION:  Although awareness of emergency contraception was high, level of
      knowledge and intention to use were low. There is a need for a targeted health
      education programme to provide accurate information about emergency
      contraception.

PMID- 30198289
TI  - Applying the Ugandan Sexual Health and Pastoral Education whole institution
      approach at the Ugandan UK Health Alliance Summit 2018.
AB  - The Ugandan UK Health alliance (UUKHA) promotes collaboration between UK- and
      Uganda-based organisations working in health in order to further global learning
      and the sharing of best practice. On 22-23 March 2018, the UUKHA held the third
      East African Health Improvement and Investment Summit in Kampala, Uganda. This is
      the report of a dynamic workshop which was aimed at encouraging thought and
      discussion on an innovative approach to tackling common health problems such as
      family planning, alcohol and malnutrition.

PMID- 30198290
TI  - Individual determinants associated with utilisation of sexual and reproductive
      health care services for HIV and AIDS prevention by male adolescents.
AB  - BACKGROUND:  Adolescent sexual and reproductive health is one of the essential
      health care programmes in the world. However, adolescents still face numerous
      challenges in the area of sexual and reproductive health, which hinder their
      utilisation of available Sexual and Reproductive HealthCare Services (SRHCS).
      Male adolescents face further obstacles in accessing and utilising sexual
      reproductive health services owing to the influence of social constructions of
      masculinity, which has a bearing on how they view sexual and reproductive health
      services and their use. OBJECTIVES:  The aim of this study was to investigate
      individual determinants associated with utilisation of SRHCS for HIV and AIDS
      prevention by male adolescents. METHOD:  An exploratory, descriptive and
      contextual qualitative design was used and semi-structured interviews with 20
      purposively selected male adolescents aged 18-24 years living in the South
      African seat of government were conducted. Data were analysed using Tesch's
      approach of data analysis. RESULTS:  Knowledge of existing services was described
      as a significant individual determinant of utilisation of SRHCS. This was linked
      to the quality of SRHCS and violation of human rights of male adolescents.
      CONCLUSION:  The study recommends the development of a strategy that will enhance
      and promote the utilisation of SRHCS by male adolescents.

PMID- 30198291
TI  - Frequency and reasons for missed appointments of outpatient mental health care
      users in the uMgungundlovu District.
AB  - BACKGROUND:  Over the years, there has been a rapid growth in the use of mobile
      technology which has been proven to increase treatment adherence. Short message
      services may improve service delivery through appointment reminders and improve
      communication between health care workers and patients. Missed appointments are
      becoming common amongst mental health care users, and this has a significant
      economic burden on mental health symptoms. OBJECTIVES:  The aim of the study was
      to determine the frequency and reasons for missed appointments of outpatient
      mental health care users for their follow-up care in the uMgungundlovu District.
      METHOD:  This study used a quantitative survey. A non-probability convenient
      sampling method was used to select 182 participants at the psychiatric clinics.
      RESULTS:  Of the 182 participants, results of the study indicated that n = 84
      (46.2%) respondents had missed their appointment at some stage. Of the n = 84
      (46.2%) respondents who had missed appointments, n = 28 (33.3%) had missed their
      appointment once, and n = 45 (53.6%) had missed their appointment 2-3 times. Most
      common reasons for missed appointments included mental health care users
      forgetting (n = 58; 69%), work commitments (n = 14; 16.7%), no transportation (n
      = 4; 4.8%) and financial constraints (n = 5; 6%). CONCLUSION:  The main reasons
      for missed appointments that were identified included forgetfulness, work
      commitments, lack of transportation and financial constraints. A significant
      number of participants (53.6%) had missed their appointments 2-3 times.

PMID- 30198292
TI  - Integration experiences of student and qualified nurses with disabilities who
      graduated from selected KwaZulu-Natal nursing education institutions: An
      exploratory case study.
AB  - BACKGROUND:  Despite the introduction of the Disability Policy Guidelines in
      South Africa (SA), student nurses who have disabilities (SNWDs) are still
      habitually and effectively excluded from nurse training programmes, and hence
      from the nursing profession. Yet SNWD may be able to offer a unique perspective.
      OBJECTIVES:  To explore and describe the integration experiences of both student
      and qualified nurses with disabilities who graduated from selected KwaZulu-Natal
      nursing education institutions (NEIs). METHOD:  A concurrent mixed-method design
      based on multiple embedded case studies served as the primary data collection
      instrument in this paper. The researcher initially conducted a survey of all the
      private NEIs to determine which had experienced training SNWDs; 3 cases and 10
      embedded cases were selected, using non-probability purposive sampling.
      Individual interviews were conducted with students and qualified nurses with who
      have a disability (n = 10) who had graduated from NEIs. RESULTS:  The findings of
      the study indicated that, largely, private NEIs are paving the way for
      integrating SNWDs; however, there are still some gaps in meeting the needs of
      these students. Despite strong legislative policies, an inclusive and enabling
      teaching and learning environment for SNWDs in nurse training remains largely
      absent. CONCLUSION:  The study recommends that NEIs develop policy guidelines for
      integrating SNWDs in nursing education programmes promoting an inclusive nursing
      education for SNWDs. The introduction of a disability liaison to assist SNWDs by
      liaising between key stakeholders and, perhaps, addressing many of the challenges
      that SNWDs experience in the clinical facilities where nursing personnel are
      unaware of their disability.

PMID- 30198294
TI  - Record-keeping: Challenges experienced by nurses in selected public hospitals.
AB  - BACKGROUND:  Patients' records provide a trace of care processes that have
      occurred and are further used as communication amongst nurses for continued
      management of patients. Nurses have the responsibility to ensure that records are
      accurate and complete in order to effectively manage their patients. In
      hospitals, nurses have to record a wide range of information in the patient's
      records and this leads to increased workload on the part of nurses that
      compromises accurate record-keeping. OBJECTIVES:  The purpose of this study was
      to explore and describe the challenges experienced by nurses with regard to
      record-keeping at selected public hospitals in the Vhembe district, Limpopo
      Province, South Africa. METHOD:  A qualitative, explorative and descriptive
      research design was used. Nurses working in selected public hospitals were
      purposively selected and semi-structured interviews were conducted until data
      saturation was reached. Data were analysed using the Tesch's open-coding method.
      RESULTS:  Nurses working in public hospitals experience record-keeping as a
      challenging activity owing to a variety of challenges which include lack of time
      to complete the records, increased patients' admission and shortage of recording
      material. CONCLUSION:  Record-keeping is not done properly which is problematic,
      and it is recommended that there should be continuous training, monitoring and
      evaluation of nurses on record-keeping issues, supply of adequate recording
      materials and proper time management amongst nurses to improve record-keeping
      challenges. The need for comprehensive record-keeping remains fundamental in
      public hospitals in order to improve patient care.

PMID- 30198293
TI  - Factors influencing enrolled nursing students' academic performance at a selected
      private nursing education institution in KwaZulu-Natal.
AB  - BACKGROUND:  The success of any educational institution is measured by its
      academic performance or how well students meet the standards set out. Currently,
      nursing students' academic failure is a phenomenon of growing international
      interest because of its economic impact and its negative effects on the
      availability of future nurses in different health care systems. Factors
      identified as influencing the academic performance of students include the socio
      economic background of parents or guardians, lecturer-student relationships,
      academic support services, demographic factors, quality of nurse educators,
      availability of facilities in the school, the language of instruction and level
      of entry qualifications of students. OBJECTIVES:  The purpose of this study was
      to describe the perceptions of enrolled student nurses on factors influencing
      their academic performance in a private nursing school in KwaZulu-Natal, South
      Africa. METHOD:  Data were collected from 100 respondents using an adapted
      instrument related to the factors believed to influence students' academic
      performance. RESULTS:  The results showed that parental involvement in education,
      good and supportive relationships between nurse educators and students, classroom
      computer technological gadgets, internet connection and adequate learning
      facilities were perceived as fostering better academic performance of students.
      In contrast, poor family background, use of English language for classroom
      instruction as well as negative peer group influences were leading to poor
      academic performance. CONCLUSION:  Nursing institutions should, therefore, select
      students with higher-level entry qualifications, early identify at-risk students,
      recruit more qualified nurse educators and upgrade their facilities.

PMID- 30198295
TI  - Support of students by academics in a nursing foundation programme at a
      university in the Western Cape.
AB  - BACKGROUND:  Owing to the inadequate schooling system and the under-preparedness
      of students in South African high schools, Higher Education Institutions are
      faced with students who do not meet the minimum criteria for acceptance into a
      mainstream programme and need support from an extended foundation programme.
      OBJECTIVES:  The study described the support of students by lecturers in an
      extended 5-year nursing foundation programme. METHOD:  A qualitative, exploratory
      and descriptive design was applied. Purposive sampling was conducted, and eight
      nursing students who completed the foundation year took part in semi-structured
      individual interviews. Each interview took around 30 min and was digitally
      recorded. Data were transcribed verbatim and analysed using open coding. Ethical
      principles and trustworthiness were maintained throughout the study. RESULTS: 
      The findings of this study indicated that experiences varied on a foundation
      programme. Participants expressed support in a nurturing environment in which the
      lecturers were open and approachable with a positive attitude. Lecturers could
      support students by being caring and advising in learning methods around the
      programme. Lecturers could focus on the method of peer support which should be
      encouraged beyond the programme so as to provide a sense of camaraderie amongst
      students. CONCLUSION:  Data revealed that support of lecturers in a foundation
      programme needs creative methods to make the learning environment nurturing for
      students. This provides for students from diverse backgrounds the opportunity to
      prepare for their studies at a university level. Insights gained from this study,
      which highlight the importance of supporting foundation students, could benefit
      all nurse educators offering foundation programmes.

PMID- 30198296
TI  - Analysis of self-evaluated ethical competence of midwifery students at a selected
      nursing college in the Free State.
AB  - BACKGROUND:  It is imperative to know whether the students who have undergone a
      specific training perceive themselves as confident and competent in handling
      ethical dilemmas, in the face of contemporary ethical challenges. Such evaluation
      is significant especially for nursing and midwifery students who have undergone
      training that stipulates adherence to a code of ethics and professional norms. At
      present, such knowledge is limited, and this has an impact for ethics education.
      OBJECTIVES:  The article aims to describe the self-evaluated ethical competence
      of midwifery students and to contrast the findings to the content of the ethics
      instruction received. Based on outcomes, the article aims to convey the claim to
      nursing institutions that current strategies that rely on teaching nursing ethics
      without appraising the context of a situation are ineffective in fostering
      ethical competence amongst students. METHOD:  This study made use of a set of
      self-reflection reports in which the midwifery nursing students narrated their
      experiences in handling ethical issues. RESULTS:  Analysis of the self-reflective
      reports revealed that one of the three dimensions of ethical competence was
      limited. There was evidence of moral perception, moral action and substandard
      moral reasoning. The principles that were mostly referred to within the
      narratives were autonomy and beneficence. CONCLUSION:  The findings support the
      argument that teaching principlism and enforcing a code of ethics without
      contextualising it coerces the student to conform without questioning their
      beliefs. Thus, ethical competence amongst the midwifery students may be described
      in terms of compliance to principles with limited reflection on the situation as
      a whole.

PMID- 30198297
TI  - The effect of body position on intraocular pressure in calves.
AB  - Tonometry is one of the basic diagnostic tests used for the diagnosis of glaucoma
      and uveitis in veterinary ophthalmology. The Icare(r) Rebound Tonometer which is
      a new tonometric device has been shown to be useful in a wide range of species.
      Eyes (n = 48) of 24 Simmental and Montafon calves with a mean age of 7.5 weeks (2
      16 weeks), male and female, were subjected to intraocular pressure (IOP)
      measurement using the Icare(r) Rebound Tonometer with calves standing and in
      lateral recumbency. The mean IOP was measured as 9.02 +/- 2.38 mmHg in the right
      eye and 9.08 +/- 2.55 mmHg in the left eye. No age-related change was found in
      intraocular pressure of the calves between 2 and 16 weeks of age. No difference
      in IOP values was observed between Simmental and Montafon calves. Body position
      had no effect on IOP in calves. The Icare(r) Rebound Tonometer was shown to be a
      suitable diagnostic device for IOP measurement in calves.

PMID- 30198299
TI  - Expression of Host Restriction Factors by Memory CD4+ T Cells Differs Between
      Healthy Donors and HIV-1-Infected Individuals with Effective Antiretroviral
      Therapy.
AB  - Much has been learnt from the functions of host restriction factors during acute
      and chronic HIV-1 infection, but far less is known about their role in HIV-1
      infected individuals in which viral load is stably suppressed with antiretroviral
      therapy (ART). In this study transcriptional expression of 42 host restriction
      factors was determined for memory CD4+ T cells sorted from 10 uninfected and 21
      HIV-1-infected individuals, treated with suppressive ART and for which the viral
      reservoir was quantified. No significant associations were observed between
      restriction factor expression and HIV-1 reservoir size, quantified by measurement
      of HIV-1 Gag DNA using droplet digital polymerase chain reaction, and by
      measurement of replication-competent inducible virus using quantitative viral
      outgrowth assays. Expression of eight of the restriction factors differed
      significantly, and with a false discovery rate of <10%, between ART-suppressed
      and uninfected individuals. APOBEC3G, ISG15, LGALS3BP, RNASEL, and MX2 were
      upregulated in the ART-suppressed individuals, likely because of increased levels
      of immune activation observed in virally suppressed compared with uninfected
      individuals. In contrast CDKN1A, TRIM11, and BRD4 were expressed at lower levels
      in ART-suppressed than uninfected individuals. This suggests perturbation of the
      CD4+ memory T cell compartment, in which a viral reservoir persists in HIV-1
      infected individuals with effective ART. Modulation of restriction factor
      expression, or overrepresentation of cell subsets that intrinsically express
      these restriction factors at lower levels could result in the distinct expression
      of restriction factors observed in treated infected individuals.

PMID- 30198298
TI  - Antibodies against Schmallenberg virus detected in cattle in the Otjozondjupa
      region, Namibia.
AB  - Several ruminant species have been shown to be susceptible to Schmallenberg virus
      (SBV), but adult animals usually recover after showing mild or no clinical signs.
      However, transplacental infection can occur and lead to abortion, malformations
      and stillborn lambs, calves and goat kids. During November and December 2014,
      malformations were observed in 11 stillborn calves from two farms in the north
      eastern region of Namibia. Blood samples were collected from 9 of the 11 cows
      that delivered stillborn and malformed calves. All these animals tested negative
      for Rift Valley fever, bovine viral diarrhoea and infectious bovine
      rhinotracheitis and were serologically positive for bluetongue virus, SBV and
      epizootic haemorrhagic disease virus. Clinical findings and serological results
      suggested that SBV may be circulating in Namibia.

PMID- 30198300
TI  - Evaluating Quality of Life in Patients With Meniere's Disease Treated as
      Migraine.
AB  - OBJECTIVE:: To evaluate the change in quality of life (QOL) of patients with
      Meniere's disease (MD) after treatment with migraine prophylaxis therapy.
      METHODS:: Patients with definite MD were given the Meniere's Disease Outcomes
      Questionnaire-Retrospective (MDOQ-R) after migraine prophylactic therapy to
      assess QOL. Changes in physical, emotional, and social parameters affected by MD
      were calculated, along with a global pre- and posttreatment QOL scores. RESULTS::
      The MDOQ-R was given to 27 consecutive patients with definite MD. Patients who
      had at least an 18-month follow-up were included, resulting in 25 questionnaires.
      The mean change in QOL score was 25 +/- 16 (range, -3 to 55), P = .02. Quality of
      life was improved in 23 (92%) of the respondents in every metric measured,
      unchanged in 1 (4%), and poorer in 1 (4%) of patients after migraine prophylaxis
      treatment. CONCLUSIONS:: Majority of MD patients who had all failed diuretic
      therapy responded positively to medications used for migraine prophylaxis, as
      indicated by a significant improvement in QOL. This study may further suggest a
      correlation between the pathophysiologic basis of disease in MD and vestibular
      migraine. Patients with MD may be successfully managed with medications intended
      to treat migraine.

PMID- 30198303
TI  - Promoting High-Value Change by Addressing the Structure of Order Sets: Lessons
      From the Cardiac Catheterization Lab.

PMID- 30198302
TI  - Neck Muscle Mass Index as a Predictor of Post-Laryngectomy Wound Complications.
AB  - OBJECTIVE: We investigated the relationship between paravertebral muscle cross
      sectional area (PVM CSA) at the third vertebra (C3) level using computerized
      tomography (CT) neck images and its relationship with complications after total
      laryngectomy. DESIGN: Retrospective analysis of 60 advanced laryngeal cancer
      patients who underwent total laryngectomy was performed. The cross-sectional
      areas of paravertebral neck muscles using neck CT at C3 level images obtained
      preoperatively were analyzed. RESULTS: A significant difference in PVM CSA
      between complication and no complication groups, F(1, 53 = 4.319, P = .043), was
      identified by ANCOVA. There were no significant differences in between-subject
      effects: T-stage ( F = 1.652, P = .204), body mass index ( F = 0.889, P = .35),
      albumin ( F = .359, P = .552), age ( F = 1.623 P = .208), and smoking ( F =
      4.319, P = .41). CONCLUSION: The PVM CSA measured at C3 level on pretreatment CT
      may help identify patients at higher risk of postoperative wound complications
      after total laryngectomy and who may particularly benefit from preoperative
      optimization of nutritional status.

PMID- 30198304
TI  - Innovative Implementation Studies Conducted in US Safety Net Health Care
      Settings: A Systematic Review.
AB  - Little is known about dissemination and implementation in safety net settings.
      The authors conducted a literature review of innovation/implementation studies in
      US safety net health care settings between 2008 and 2017. Each article was coded
      for (1) intervention characteristics, (2) implementation stage, (3) internal
      versus external ownership, and (4) prespecified implementation outcomes (eg,
      acceptability and fidelity). Twenty studies were identified; the majority were
      implemented within community clinics or integrated safety net systems (15
      articles), most involved care process improvements (13 articles), and most were
      internally developed (13 articles). The internally developed innovations reported
      fewer barriers to acceptability among staff/providers, higher leadership
      involvement and organizational alignment, greater amounts of customization to the
      local setting, and better sustainment. Future work should harness the high levels
      of alignment and acceptability in implementation research within safety net
      settings, with an eye toward maintaining fidelity to facilitate dissemination
      across sites.

PMID- 30198306
TI  - Bringing binge eating disorder into focus: The sidelined eating disorder.

PMID- 30198305
TI  - Milnacipran: serotonin-noradrenaline reuptake inhibitor approved for fibromyalgia
      may be a useful antidepressant.
AB  - OBJECTIVE: Milnacipran is a serotonin noradrenaline reuptake inhibitor (SNRI)
      approved for treatment of fibromyalgia in Australia, but is used for depression
      in Europe and elsewhere. This paper will briefly review milnacipran and its
      utility in psychiatry for the treatment of depression. CONCLUSION: Milnacipran is
      a dual reuptake inhibitor of noradrenaline and serotonin, with greater effect on
      noradrenaline than serotonin, in contrast to the related drugs venlafaxine,
      desvenlafaxine and duloxetine. Rapidly absorbed irrespective of food, milnacipran
      has a half-life of approximately 8 hours, reaches steady state in 2 days and is
      excreted renally. Milnacipran helps a minority of patients with fibromyalgia by
      reducing pain and fatigue. It is also an effective antidepressant with efficacy
      comparable to venlafaxine and duloxetine, and a side effect profile
      characteristic of SNRIs. The dose range is 50-200 mg, in divided doses.
      Milnacipran may be useful for patients with depression and pain, and endogenous
      depression characterised by anergia, psychomotor retardation and hypersomnia.
      Caution is necessary in the presence of heart disease, hypertension, renal
      impairment, epilepsy, glaucoma, bipolar disorder, and bleeding tendency.
      Milnacipran is likely to be a useful late antidepressant option in treatment
      resistant patients, as well as those with chronic pain, anergia and hypersomnia.

PMID- 30198307
TI  - Nrf2 Sequesters Keap1 Preventing Podosome Disassembly: A Quintessential Duet
      Moonlights in Endothelium.
AB  - AIMS: Nrf2 (nuclear factor erythroid 2-like 2) is a transcription factor known to
      modulate blood vessel formation. Various experimental settings, however,
      attribute to Nrf2 either stimulatory or repressive influence on angiogenesis. Our
      findings unveil the mechanism of Nrf2-dependent vessel formation, which reaches
      beyond transactivation of gene expression and reconciles previous discrepancies.
      RESULTS: We provide evidence that growth differentiation factor 15 (GDF-15)- and
      stromal cell-derived factor 1 (SDF-1)-induced angiogenesis strongly depends on
      the presence of Nrf2 protein but does not rely on its transcriptional activity.
      Instead, Nrf2 serves as a protein restraining Keap1 (Kelch-like ECH-associated
      protein 1), its known transcriptional repressor. Angiogenic response is abrogated
      in Nrf2-deficient endothelial cells but not in cells expressing dominant negative
      form or Keap1-binding fragment of Nrf2. Deficiency of Nrf2 protein available for
      Keap1 leads to the overabundance of RhoGAP1 (Rho GTPase-activating protein 1),
      the protein regulating cell division cycle 42 (Cdc42) activity. This impairs
      podosome assembly and disrupts actin rearrangements, thereby preventing
      angiogenesis. Effects of Nrf2 deficiency can be rescued by concomitant knockdown
      of RhoGAP1 or Keap1. Importantly, in the established murine model of Nrf2
      deficiency, the N-terminal fragment of Nrf2 containing Keap1 binding domain is
      preserved. Thus, this model can be used to characterize Nrf2 as a transcription
      factor, but not as a Keap1-sequestering protein. Innovation and Conclusion: To
      date, the significance of Nrf2 in cell function has been ascribed solely to the
      regulation of transcription. We demonstrate that Nrf2 serves as a protein
      tethering Keap1 to allow podosome assembly and angiogenesis. Moreover, we
      emphasize that the new Nrf2 function of a Keap1 scavenger implies revisiting the
      interpretation of some of the previous data on the Nrf2-Keap1 system. Antioxid.
      Redox Signal. 00, 000-000.

PMID- 30198308
TI  - Referrals for Hypoglycemia to the Pediatric Endocrine Clinic: Is It For Real?

PMID- 30198309
TI  - Biological Processes and Biomarkers Related to Frailty in Older Adults: A State
      of-the-Science Literature Review.
AB  - The objectives of this literature review were to (1) synthesize biological
      processes linked to frailty and their corresponding biomarkers and (2) identify
      potential associations among these processes and biomarkers. In September 2016,
      PubMed, Cumulative Index to Nursing and Allied Health, Cochrane Library, and
      Embase were searched. Studies examining biological processes related to frailty
      in older adults (>=60 years) were included. Studies were excluded if they did not
      employ specific measures of frailty, did not report the association between
      biomarkers and frailty, or focused on nonelderly samples (average age < 60).
      Review articles, commentaries, editorials, and non-English articles were also
      excluded. Fifty-two articles were reviewed, reporting six biological processes
      related to frailty and multiple associated biomarkers. The processes (biomarkers)
      include brain changes (neurotrophic factor, gray matter volume), endocrine
      dysregulation (growth hormones [insulin-like growth factor-1 and binding
      proteins], hormones related to glucose and insulin, the vitamin D axis, thyroid
      function, reproductive axis, and hypothalamic-pituitary-adrenal axis), enhanced
      inflammation (C-reactive protein, interleukin-6), immune dysfunction
      (neutrophils, monocytes, neopterin, CD8+CD28-T cells, albumin), metabolic
      imbalance (micronutrients, metabolites, enzyme-activity indices, metabolic end
      products), and oxidative stress (antioxidants, telomere length,
      glutathione/oxidized glutathione ratio). Bidirectional interrelationships exist
      within and between these processes. Biomarkers were associated with frailty in
      varied strengths, and the causality remains unclear. In conclusion, frailty is
      related to multisystem physiological changes. Future research should examine the
      dynamic interactions among these processes to inform causality of frailty. Given
      the multifactorial nature of frailty, a composite index of multisystem biomarkers
      would likely be more informative than single biomarkers in early detection of
      frailty.

PMID- 30198310
TI  - A Coordinated Analysis of Variance in Affect in Daily Life.
AB  - Despite widespread interest in variance in affect, basic questions remain
      pertaining to the relative proportions of between-person and within-person
      variance, the contribution of days and moments, and the reliability of these
      estimates. We addressed these questions by decomposing negative affect and
      positive affect variance across three levels (person, day, moment), and
      calculating reliability using a coordinated analysis of seven daily diary,
      ecological momentary assessment (EMA), and diary-EMA hybrid studies (across
      studies age = 18-84 years, total Npersons = 2,103, total Nobservations = 45,065).
      Across studies, within-person variance was sizeable (negative affect: 45% to 66%,
      positive affect: 25% to 74%); in EMA more within-person variance was attributable
      to momentary rather than daily level. Reliability was adequate to high at all
      levels of analysis (within-person: .73-.91; between-person: .96-1.00) despite
      different items and designs. We discuss the implications of these results for the
      design of future intensive studies of affect variance.

PMID- 30198311
TI  - Rotational Thromboelastometry for Assessing Bleeding Complications and Factor
      XIII Deficiency in Cardiac Surgery Patients.
AB  - We aimed to detect alterations and deficits in hemostasis during cardiac surgery
      with cardiopulmonary bypass (CPB) using point-of-care-supported coagulation
      analysis (rotational thromboelastometry, impedance aggregometry), in addition to
      single factor assays for the measurement of fibrinogen (FI) and factor XIII
      (FXIII) levels. Forty-one patients scheduled for elective cardiac surgery with
      CPB were enrolled in this observational study. Perioperative measurement (pre-,
      postheparin, 30-minutes before the end of bypass, 1-hourpostoperatively) of
      standard laboratory variables, additional rotational thromboelastometry (ROTEM;
      International GmbH, Munich, Germany), Multiplate analysis (Roche, Switzerland),
      and an assay of FXIII activity were performed as well as the collection of
      epidemiological data and blood loss. The FI and FXIII levels as well as the
      measured ROTEM and Multiplate parameters correlated weakly with the blood loss.
      Clotting time and maximum clot firmness (MCF) of the intrinsically activated
      ROTEM showed a good correlation ( rCT-INTEM = 0.378; P < .05, rMCF-INTEM = 0.305;
      P < .05) with postoperative drainage loss, suggesting a dependence of blood loss
      on the initial intrinsic activity. Additionally, perioperative FI or FIBTEM
      levels and the FXIII levels correlated with each other. Intrinsically activated
      ROTEM showed a good correlation with postoperative drainage loss, thus suggesting
      a dependence of blood loss on the initial intrinsic activity and therefore
      facilitating clinicians to assess postoperative bleeding complications. Based on
      the FI level or the MCFFIBTEM measured by ROTEM, it may also be possible to
      assess the FXIII concentration. Especially in chronically ill and massive
      bleeding cardiac surgery patients with significantly decreased FXIII levels, the
      knowledge of FXIII deficiency may help clinicians to treat coagulation disorders
      more adequately.

PMID- 30198313
TI  - Smokers with children with asthma: Parental perceptions about prototype
      intervention messages focused on reducing child tobacco exposure and use.
AB  - Formative research is needed to develop effective interventions that eliminate
      secondhand smoke exposure (SHSe) and prevent tobacco use (TU) among children with
      asthma. This online study included 300 parents who smoke and had a child with
      asthma (ages 10-14) and evaluated their perceptions about prototypes of parent
      directed and child-directed feedback intervention messages focused on reducing
      child SHSe and future TU; correlates of perceptions were explored. Parents rated
      examples of parent-directed messages on motivation and helpfulness for
      eliminating SHSe and promoting conversations about TU and also rated child
      directed messages on acceptability and helpfulness for promoting conversations
      about TU. Messages differed by level of personalization, theoretical background,
      or message content. Parents found all parent-directed messages similarly
      motivating and helpful and all child-directed messages similarly acceptable and
      helpful for reducing child tobacco exposure. Differences in perceptions about
      feedback emerged based on parent gender, parent readiness to quit, smoking ban
      status, and the presence of additional smokers in the home. Overall, parents
      rated parent-directed and child-directed feedback message prototypes positively,
      including established and novel types of feedback. Parent-child feedback
      interventions may hold promise for breaking the intergenerational transmission of
      smoking among families with a parent who smokes and a child with asthma.

PMID- 30198314
TI  - Making the Most of Your Research Budget: Efficiency of a Three-Method Measurement
      Design With Planned Missing Data.
AB  - Planned missing data (PMD) designs are an elegant way to incorporate expensive
      gold standard methods (e.g., biomarker) and cheaper but systematically biased
      methods (e.g., questionnaires) in research designs while ensuring high
      statistical power and low research costs. This article outlines a PMD design with
      one expensive gold standard and two cheap but biased methods (three-method
      measurement [3-MM] design). The cost effectiveness of different 3-MM-PMD designs
      is investigated and compared with the cost effectiveness of corresponding same
      price two-method measurement designs using a simulation study. The results
      underline that PMD designs yield higher statistical power compared with complete
      data designs in a wide variety of conditions. Adding a second cheap method to the
      measurement model (i.e., using a 3-MM-PMD design) can increase the statistical
      power of the research design even further while keeping costs constant, when the
      additional measure is inexpensive, shares only small amounts of bias variance
      with the initial cheap measure, and when the gold standard measure is highly
      expensive compared with the cheap measures. Recommendations as well as a computer
      program for finding the optimal research design are provided.

PMID- 30198312
TI  - Problem Drinking, Alcohol Expectancy, and Thalamic Resting-State Functional
      Connectivity in Nondependent Adult Drinkers.
AB  - Alcohol misuse is associated with thalamic dysfunction. The thalamus comprises
      subnuclei that relay and integrate information between cortical and subcortical
      structures. However, it is unclear how the subnuclei contribute to thalamic
      dysfunctions in problem drinking. We investigated resting-state functional
      connectivity (rsFC) of thalamic subregions in 107 nondependent drinkers (57
      women), using masks delineated by white matter tractography. Thalamus was
      parceled into motor, somatosensory, visual, premotor, frontal association,
      parietal association, and temporal association subregions. Whole-brain linear
      regression, each against Alcohol Use Disorders Identification Test (AUDIT) and
      positive alcohol expectancy (AE) score with age as a covariate, was performed for
      each seed, for men and women combined, and separately. Overall, problem drinking
      was associated with increased thalamic connectivities, whereas AE was associated
      with a mixed pattern of increased and decreased connectivities. Motor, premotor,
      somatosensory, and frontal association thalamic connectivity with bilateral
      caudate head was positively correlated with AUDIT score in men and women
      combined. Connectivity of the right caudate head with frontal association and
      premotor thalamus was also positively correlated with AE score in men and women
      combined. In contrast, motor and premotor thalamic connectivity with a number of
      cortical and subcortical structures showed sex differences in the correlation
      each with AUDIT and AE score. In mediation analyses, AE score completely mediated
      the correlation between thalamic caudate connectivity and AUDIT score, whereas
      the model where AE contributed to problem drinking and, in turn, altered thalamic
      caudate connectivity was not supported. To conclude, thalamic subregional rsFCs
      showed both shared and distinct changes and sex differences in association with
      problem drinking and AE. Increased thalamic caudate connectivity may contribute
      to problem drinking via enhanced AE. The findings suggest the importance of
      examining thalamic subdivisions and sex in investigating the functional roles of
      thalamus in problem drinking.

PMID- 30198315
TI  - Comparative Pharmacokinetic Profile of 3 Batches of Ovine Low-Molecular-Weight
      Heparin and 1 Batch of Branded Enoxaparin.
AB  - Although pharmaceutical grade heparin is obtained almost exclusively from porcine
      intestinal mucosa, there is interest in diversifying heparin sourcing to address
      potential supply shortages and economically motivated adulteration. Since ovine
      derived heparin is structurally similar to porcine heparin, it is expected that
      ovine-derived low-molecular-weight heparin (LMWH) will be comparable to porcine
      derived LMWH. This study compared the pharmacokinetic (PK) behavior of 3 batches
      of ovine LMWH with that of enoxaparin in nonhuman primates. Blood samples were
      collected prior to and at 2, 4, and 6 hours post-administration of a 1 mg/kg
      subcutaneous dose of LMWH. Circulating drug concentrations determined using anti
      Xa and anti-thrombin assays were used to calculate values for PK parameters.
      Tissue factor pathway inhibitor (TFPI) levels were measured by enzyme-linked
      immunosorbent assay. The ovine LMWHs tested met pharmacopoeial potency and
      molecular weight distribution requirements for enoxaparin. In the post
      administration samples, comparable levels of branded enoxaparin and ovine
      enoxaparin were observed using anti-Xa and anti-thrombin assays, with the
      concentration versus time curves being nearly superimposable. Consistent with
      this similarity, no significant differences were observed between PK parameters
      calculated for branded enoxaparin and ovine LMWH. The TFPI levels returned to
      baseline levels by 6 hours in ovine LMWH-treated animals but remained slightly
      elevated in animals treated with branded enoxaparin. It is concluded that the
      pharmacokinetics of ovine enoxaparin were not only comparable between different
      batches but also similar to the branded product. Thus, LMWH prepared from ovine
      mucosal heparin is comparable to its porcine-derived counterpart.

PMID- 30198316
TI  - Impact of Emergency Shelter Utilization and Kinship Involvement on Children's
      Behavioral Outcomes.
AB  - Youth in child welfare often experience emergency shelter care, a type of
      congregate setting, while a permanent placement is arranged. The present
      longitudinal study explored the impact of initial emergency shelter placement on
      long-term externalizing behavior (i.e., aggression, delinquency) and
      internalizing symptom (i.e., anxiety, depression) trajectories, and whether
      kinship involvement moderated the effect of shelter placement on behavioral
      outcomes. The sample consisted of 282 youths (55.3% male) with an average age of
      9.90 years ( SD = 2.37); 36.9% experienced an emergency shelter placement. Data
      were collected from the Illinois Department of Children and Family Services.
      Caseworkers completed the Child and Adolescent Needs and Strengths, which
      measured youths' behavioral outcomes. Results suggested that shelter care was not
      associated with externalizing behavior trajectories. However, shelter care was
      associated with internalizing symptoms among children with less kinship
      involvement. Results from this study suggest that best practices for shelter care
      should leverage kinship involvement.

PMID- 30198317
TI  - Prediction of Early Death in Patients With Sepsis-Associated Coagulation Disorder
      Treated With Antithrombin Supplementation.
AB  - For success in clinical trials, eliminating inclusion of patients with
      irreversible recovery is important. The purpose of this study was to identify the
      patient population who do not survive for more than 3 days. A total of 449
      patients with sepsis suspected of having disseminated intravascular coagulation
      (DIC) and treated with antithrombin were examined. The patient characteristics,
      baseline sequential organ failure assessment (SOFA) score, DIC score, and
      hemostatic markers were retrospectively analyzed in relation to early death (died
      within 3 days). At the end of day 3, a total of 419 patients had survived and 30
      patients had died. A logistic regression analysis revealed a significant
      association between early death and the baseline prothrombin time-international
      normalized ratio PT-INR ( P <.05) and the total SOFA score ( P <.01). In
      contrast, neither the platelet count, fibrinogen/fibrin degradation products, and
      antithrombin activity nor the DIC score was associated with early death. Although
      the accuracy for predicting early death defined by either baseline PT-INR of
      >=1.57 or total SOFA score of more than 13 was not high enough, that of "high
      risk of early death (PT-INR >= 1.57 and SOFA score >= 13)" was 83.5%.
      Furthermore, the negative predictive of this category was 96.0%. The baseline
      SOFA score and PT-INR were associated with early death among patients with sepsis
      associated coagulation disorders. Patients who do not meet the "high-risk of
      early death" criteria were likely to survive for more than 3 days and therefore
      should be considered for future therapeutic clinical trials.

PMID- 30198318
TI  - Effects of Heart Rate Reduction With Either Pyridostigmine or Ivabradine in
      Patients With Heart Failure: A Randomized, Double-Blind Study.
AB  - BACKGROUND: Heart rate (HR) reduction with ivabradine has been proved to reduce
      hospitalization and death from heart failure (HF). We sought to investigate
      whether pyridostigmine would effectively reduce HR in patients with chronic HF as
      compared with ivabradine. METHODS: Twenty-one patients with HF who were in sinus
      rhythm with a resting HR over 70 bpm, despite optimal medical treatment, were
      included in a randomized, double-blind study comparing pyridostigmine versus
      ivabradine. The initial dose of ivabradine was 5 mg twice daily to reach a target
      HR between 50 and 60 bpm and could be titrated to a maximum of 7.5 mg twice
      daily. Pyridostigmine was used in a fixed dose of 30 mg 3 times daily. RESULTS:
      The baseline HR for ivabradine and pyridostigmine groups was 89.1 (13.5) and 80.1
      (7.2) bpm, respectively ( P = .083). After 6 months of treatment, HR was
      significantly reduced to 64.8 (8.3) bpm in the ivabradine group ( P = .0014) and
      63.6 (5.9) bpm in the pyridostigmine group ( P = .0001). The N-terminal pro-B
      type natriuretic peptide was reduced in the ivabradine group (median: 1308.4
      [interquartile range: 731-1896] vs 755.8 [134.5-1014] pg/mL; P = .027) and in the
      pyridostigmine group (132.8 [89.9-829] vs 100.7 [38-360] pg/mL; P = .002).
      Inflammatory markers interleukin-1, interleukin-6, and tumor necrosis factor were
      reduced in both groups. Exercise capacity was improved in both groups, with
      increments in volume of oxygen utilization ([Formula: see text]O2; ivabradine:
      13.1 vs 15.6, P = .048; pyridostigmine: 13.3 vs 16.7, P = .032). Heart rate
      recovery in the first minute postexercise was improved with pyridostigmine (11.8
      [3.9] vs 18 [6.5]; P = .046), but not with ivabradine (13.3 [6.9] vs 14.1 [8.2];
      P = .70). No differences in either group were observed in the myocardial
      scintigraphy with 123-iodine-metaiodobenzylguanidine. CONCLUSION: Both drugs
      significantly reduced HR, with improvements in exercise capacity and in
      neurohormonal and inflammatory profiles.

PMID- 30198319
TI  - Measuring Psychological Inflexibility in Children and Adolescents: Evaluating the
      Avoidance and Fusion Questionnaire for Youth.
AB  - The Avoidance and Fusion Questionnaire for Youth (AFQ-Y8) was developed to
      measure psychological inflexibility. Although the questionnaire is a well-known
      tool in clinical practice, its psychometric properties have not been widely
      investigated in the target population of children and adolescents. The purpose of
      this study was to investigate the factor structure and validity of the AFQ-Y8 ( N
      = 1,572, mean age 15.39 years, girls 51%) on a Hungarian sample. We also tested
      the invariance of the measurement model across two age groups (11-14 and 15-20
      years old). Results confirmed the single-factor structure of the AFQ-Y8.
      Psychological inflexibility was also found to be positively related to emotional
      instability, externalizing, and internalizing problems. Furthermore,
      psychological inflexibility explained the variance of life satisfaction when
      personality dimensions, emotional, and behavioral problems were accounted for.
      Measurement invariance across age groups was partially supported. These results
      suggest that the AFQ-Y8 is a reliable and valid instrument for assessing
      psychological inflexibility in children and adolescents.

PMID- 30198321
TI  - Risk Assessment in Chinese Hospitalized Patients Comparing the Padua and Caprini
      Scoring Algorithms.
AB  - The current venous thromboembolism (VTE) guidelines recommend all patients to be
      assessed for the risk of VTE using risk assessment models (RAMs). The study was
      to evaluate the performance of the Caprini and Padua RAMs among Chinese
      hospitalized patients. We reviewed data from 189 patients with deep venous
      thrombosis (DVT) and 201 non-DVT patients. Deep venous thrombosis risk factors
      were obtained from all patients. The sensitivity and specificity of the Caprini
      and Padua scores for all patients were calculated. The receiver operating curve
      (ROC) and the area under the ROC curve (AUC) were used to evaluate the
      performance of each score. We documented that age, acute infection, prothrombin
      time (PT), D-dimer, erythrocyte sedimentation rate, blood platelets, and
      anticoagulation were significantly associated with the occurrence of DVT ( P <
      .05). These results were true for all medical and surgical patients group (G1),
      as well as the analysis of medical versus surgical patients (G2). Finally,
      analysis of the scores in patients with and without cancer was also done (G3).
      The Caprini has a higher sensitivity but a lower specificity than the Padua ( P <
      .05). Caprini has a better predictive ability for the first 2 groups ( P < .05).
      We found Caprini and Padua scores have a similar predictive value for patients
      with cancer ( P > .05), while Caprini has a higher predictive ability for no
      cancer patients in G3 than Padua ( P < .05). For Chinese hospitalized patients,
      Caprini has a higher sensitivity but a lower specificity than Padua. Overall,
      Caprini RAM has a better predictive ability than Padua RAM.

PMID- 30198320
TI  - Improvement of late life depression after therapeutic enoxaparin: two case
      reports.
AB  - OBJECTIVE: Late life depression (LLD) may have a significant vascular component.
      While this organic basis remains controversial it would explain the refractory
      nature of LLD. Moreover, depression is a risk factor for venous thrombus embolism
      (VTE). This paper aims to describe two elderly patients with LLD who developed
      and were treated for pulmonary embolism (PE). METHODS: Two cases of elderly
      patients who developed PE while they were undergoing inpatient treatment for
      depression are presented. This is discussed using the vascular and the cytokine
      hypotheses of depression as an explanatory framework. RESULTS: Both patients
      showed significant clinical improvement in their mental state following
      therapeutic enoxaparin despite no other changes to their management of
      depression. This observed benefit of enoxaparin can be explained by the vascular
      hypothesis of LLD, and possibly the cytokine hypothesis of major depression.
      CONCLUSION: Enoxaparin may be a novel adjunct to the treatment of depression in
      elderly patients. The possible benefit of enoxaparin would require further study
      to exclude a coincidence in these clinical cases.

PMID- 30198322
TI  - Quantifying Graphene Oxide Reduction Using Spectroscopic Techniques: A
      Chemometric Analysis.
AB  - The surface chemistry of graphene oxide (GO) can be modified by the chemical
      reduction of oxygen-containing groups using L-ascorbic acid (L-AA). Being able to
      "tune" the surface hydrophobicity of GO in a controlled manner, with a well
      defined level of reduction, provides a valuable tool for understanding and
      controlling interactions with hydrophobic surfaces. Numerous analytical and
      chemical methods have been used to determine the extent of reduction in
      chemically reduced graphene oxide (CRGO) samples. However, many of these methods
      are limited by their laborious nature, cost, or lack of sensitivity in resolving
      oxygen content in samples that have only been reduced for short periods of time,
      making them inappropriate for rapid use with multiple samples. Here, we have used
      ultraviolet (UV), Raman, and attenuated total reflection infrared (ATR-IR)
      spectroscopy to monitor the chemical reduction of GO. These three techniques are
      simple, rapid, nondestructive, accurate, and widely available. The data set from
      each technique has been correlated and modeled against a reference data set
      (carbon to oxygen ratio obtained from elemental analysis) using partial least
      squares regression (PSLR). Using this approach, the chemical reduction of GO was
      quantified from UV (r2 = 0.983, RMSECV = 0.049), Raman (r2 = 0.961, RMSECV =
      0.073) and ATR-IR (r2 = 0.993, RMSECV = 0.032) data. ATR-IR enabled
      identification of the different oxygen-containing groups on GO, and coupled with
      chemometric modeling, provides an excellent approach for the routine quantitative
      analysis of the chemical reduction of GO.

PMID- 30198323
TI  - Characteristic Fluctuations Around Stable Attractor Dynamics Extracted from
      Highly Nonstationary Electroencephalographic Recordings.
AB  - Since the discovery of electrical activity of the brain, electroencephalographic
      (EEG) recordings constitute one of the most popular techniques of brain research.
      However, EEG signals are highly nonstationary and one should expect that averages
      of the cross-correlation coefficient, which may take positive and negative values
      with equal probability, (almost) vanish when estimated over long data segments.
      Instead, we found that the average zero-lag cross-correlation matrix estimated
      with a running window over the whole night of sleep EEGs, or of resting state
      during eyes-open and eyes-closed conditions of healthy subjects shows a
      characteristic correlation pattern containing pronounced nonzero values. A
      similar correlation structure has already been encountered in scalp EEG signals
      containing focal onset seizures. Therefore, we conclude that this structure is
      independent of the physiological state. Because of its pronounced similarity
      across subjects, we believe that it depicts a generic feature of the brain
      dynamics. Namely, we interpret this pattern as a manifestation of a dynamical
      ground state of the brain activity, necessary to preserve an efficient
      operational mode, or, expressed in terms of dynamical system theory, we interpret
      it as a "shadow" of the evolution on (or close to) an attractor in phase space.
      Nonstationary dynamical aspects of higher cerebral processes should manifest in
      deviations from this stable pattern. We confirm this hypothesis through a
      correlation analysis of EEG recordings of 10 healthy subjects during night sleep,
      20 recordings of 9 epilepsy patients, and 42 recordings of 21 healthy subjects in
      resting state during eyes-open and eyes-closed conditions. In particular, we show
      that the estimation of deviations from the stationary correlation structures
      provides a more significant differentiation of physiological states and more
      homogeneous results across subjects.

PMID- 30198324
TI  - Development and Implementation of a Subcutaneous Insulin Clinical Decision
      Support Tool for Hospitalized Patients.
AB  - BACKGROUND: Insulin is one of the highest risk medications used in hospitalized
      patients. Multiple complex factors must be considered in determining a safe and
      effective insulin regimen. We sought to develop a computerized clinical decision
      support (CDS) tool to assist hospital-based clinicians in insulin management.
      METHODS: Adapting existing clinical practice guidelines for inpatient glucose
      management, a design team selected, configured, and implemented a CDS tool to
      guide subcutaneous insulin dosing in non-critically ill hospitalized patients at
      two academic medical centers that use the EpicCare(r) electronic medical record
      (EMR). The Agency for Healthcare Research and Quality (AHRQ) best practices in
      CDS design and implementation were followed. RESULTS: A CDS tool was developed in
      the form of an EpicCare SmartForm, which generates an insulin regimen by
      integrating information about the patient's body weight, diabetes type, home and
      hospital insulin requirements, and nutritional status. Total daily recommended
      insulin doses are distributed into respective basal and nutritional doses with a
      tailored correctional insulin scale. Preimplementation, several approaches were
      used to communicate this new tool to clinicians, including emails, lectures, and
      videos. Postimplementation, a support team was available to address user
      technical issues. Feedback from stakeholders has been used to continuously refine
      the tool. Inclusion of the programming in the EMR vendor's community library has
      allowed dissemination of the tool outside our institution. CONCLUSIONS: We have
      developed an EMR-based tool to guide SQ insulin dosing in non-critically ill
      hospitalized patients. Further studies are needed to evaluate adoption and
      clinical effectiveness of this intervention.

PMID- 30198325
TI  - The beneficial effect of probiotics as a supplementary treatment in drug
      resistant epilepsy: a pilot study.
AB  - Epilepsy is a neurological disease with high global prevalence. Despite the range
      of drug-based treatments currently available to control the condition, one in 3
      patients experiences epileptic seizures. Therapeutic alternatives for these
      patients include the ketogenic diet, surgery or the cerebral implantation of
      neurostimulators; however these are benefits with limits. The target of this
      study is to find a new complementary treatment for these patients, studying the
      effectiveness of probiotics for controlling epileptic seizures in patients with
      drug-resistant epilepsy. A prospective study was designed in which a group of
      patients with drug-resistant epilepsy was administered a probiotic mixture for 4
      months. Patients were assessed before and after taking the probiotics; among
      other variables, number of seizures and patients' quality of life (QOLIE-10) were
      monitored. Levels of cD-14, interleukin 6, and gamma-aminobutyric acid were also
      analysed throughout the study. 45 patients were included in the study. In an
      intention-to-treat analysis, 28.9% of all patients displayed a greater than 50%
      reduction in the number of seizures (the parameter required in clinical trials).
      A significant improvement was also observed in patients' quality of life. We
      found that probiotics may be an option for supplementary therapy. Since the use
      of probiotics is safe, they may contribute to improving seizure control, and
      therefore quality of life, in patients with drug-resistant epilepsy. The study
      has been registered in https://clinicaltrials.gov with number NCT03403907.

PMID- 30198326
TI  - Effect of combined bifidobacteria supplementation and resistance training on
      cognitive function, body composition and bowel habits of healthy elderly
      subjects.
AB  - Physical exercise exerts favourable effects on brain health and quality of life
      of the elderly; some of these positive health effects are induced by the
      modulation of microbiota composition. We therefore conducted a randomised, double
      blind, placebo-controlled trial that assessed whether a combination of
      Bifidobacterium spp. supplementation and moderate resistance training improved
      the cognitive function and other health-related parameters in healthy elderly
      subjects. Over a 12-week period, 38 participants (66-78 years) underwent
      resistance training and were assigned to the probiotic Bifidobacterium
      supplementation (n=20; 1.25*1010 cfu each of Bifidobacterium longum subsp. longum
      BB536, B. longum subsp. infantis M-63, Bifidobacterium breve M-16V and B. breve B
      3) or the placebo (n=18) group. At baseline and at 12 weeks, we assessed the
      cognitive function, using the Japanese version of the Montreal Cognitive
      Assessment instrument (MoCA-J); modified flanker task scores; depression-anxiety
      scores; body composition; and bowel habits. At 12 weeks, the MoCA-J scores showed
      a significant increase in both the groups, while the flanker task scores of the
      probiotic group increased more significantly than those of the placebo group
      (0.35+/-0.9 vs -0.29+/-1.1, P=0.056). Only the probiotic group showed a
      significant decrease in the depression-anxiety scores (5.2+/-6.3 to 3.4+/-5.5,
      P=0.012) and body mass index (24.0+/-2.8 to 23.5+/-2.8 kg/m2, P<0.001), with a
      significant increase in the defecation frequency (5.3+/-2.3 to 6.4+/-2.3 times/5
      days, P=0.023) at 12 weeks. Thus, in healthy elderly subjects, combined probiotic
      bifidobacteria supplementation and moderate resistance training may improve the
      mental condition, body weight and bowel movement frequency.

PMID- 30198327
TI  - Mind the gut: probiotics in paediatric neurogastroenterology.
AB  - The gut-brain axis has recently emerged as a key modulator of human health and
      the intestinal microbiome has a well-recognised pivotal role in this strong
      connection. The aim of this narrative review is to update and summarise the
      effect and clinical applicability of probiotics in paediatric
      neurogastroenterology. The Cochrane Database and PubMed were searched using
      keywords relating to different subtypes of functional gastrointestinal disorders
      (FGIDs) and their symptoms, those relating to the CNS and related neurological or
      behavioural dysfunction as well as 'probiotic' OR 'probiotics'. Included papers
      were limited to those including children (aged 0-18 years) and using English
      language. Although significant effects of specific strains have been reported in
      infants with FGIDs, heterogeneity amongst the studies (different products and
      concentrations used and FGID subtypes), has limited the ability to draw an
      overall conclusion on the clinical value of probiotics. According to different
      meta-analyses of randomised controlled trials, the use of Lactobacillus reuteri
      (DSM 17938) was associated with a significant decrease in average crying time in
      infantile colic. There is moderate evidence for this strain and LGG and limited
      evidence (based on one study each) for the beneficial effect of VSL#3 and a three
      strain bifidobacteria mix in abdominal pain FGIDs, particularly in the irritable
      bowel disease subgroup of children, but not in functional dyspepsia. There is
      currently no clear evidence of positive effects of oral probiotics in autistic
      spectrum disorder. Efficacy and safety of other strains or beneficial effects in
      other conditions still need to be proven, as probiotic properties are strain
      specific, and data cannot be extrapolated to other brain-gut or mood diseases or
      to other probiotics of the same or different species. To transform the use of
      probiotics from a tempting suggestion to a promising treatment modality in
      neurogastroenterological disorders more accurate differentiation of the efficacy
      proven strains, clarification of dose, duration, and outcome and a careful
      selection of the target patients are still necessary.

PMID- 30198328
TI  - Correlations Between Cognitive Aspects and Quantitative EEG in Adults With
      Epilepsy.
AB  - INTRODUCTION: Cognitive impairment frequently occurs in adult patients with
      epilepsy (PWE), but its pathophysiological basis is not well known. This study
      assessed cognition and its correlations with quantitative EEG coherence (QEEG) of
      patients with epilepsy. METHOD: Eighty PWE seen consecutively in the clinic and
      40 normal subjects (NC) were assessed by neurological evaluation, Mini Mental
      State Examination, immediate and delayed recall of 10 simple figures, phonemic
      verbal fluency (FAS), category fluency test (VF animals), clock drawing, and
      QEEG. The mean global inter- and intrahemispheric coherences for the delta,
      theta, alpha, and beta bands were calculated. Cognitive functions and QEEG
      coherence of the PWE and the NC were compared, and logistic regression analysis
      determined the factors associated with impaired cognitive functions in PWE. The
      significance level was set at P < .05. RESULTS: Regression analysis showed that
      FAS impairment (14.5 +/- 8.6 vs 24.3 +/- 15.7, respectively) and delayed recall
      of figures in PWE (7.3 +/- 2.07 vs 8.6 +/- 1.48) differed significantly between
      the PWE and the NC (Nagelkerke R2 = 0.266). Absolute power was greater in all the
      frequency bands in PWE. Interhemispheric and intrahemispheric beta coherences in
      the theta frequency was higher in the PWE than in the NC. Logistic regression
      analysis showed a significant association between interhemispheric delta
      coherence and VF animal impairment (cutoff point of 12), and between an
      interhemipheric beta coherence with level of education and delayed recall of
      figures impairment (cutoff point of 7) (Nagelkerke R2 = 0.297). Other variables
      were not associated. CONCLUSIONS: There was cognitive impairment of PWE and it
      was significantly associated with QEEG, which suggests that QEEG measures may
      contribute to the understanding of physiopathological events and as a marker for
      cognitive alterations in epilepsy.

PMID- 30198329
TI  - Stability and visual outcomes yielded by three intraocular trifocal lenses with
      same optical zone design but differing material or toricity.
AB  - PURPOSE: To compare rotational stability, centration and visual outcomes provided
      by three trifocal lens models that have the same optical zone design but
      different material, composition, and/or toricity. METHODS: The study included 78
      patients with symmetric bilateral intraocular lens implantation. The lenses under
      evaluation were trifocal intraocular lenses made of hydrophilic acrylic material:
      a spherical lens 26% hydrophilic acrylic (POD FineVision), a similar lens but
      having a toric design (POD Toric FineVision), and a trifocal lens 25% hydrophilic
      acrylic material (FineVision/MicroF). Moreover, the lenses share the same optical
      zone design. The lenses' rotational stability and centration were measured by
      means of the PIOLET software, which relies on recording and image processing
      techniques to determine lens rotation and centration based on slit-lamp images.
      We also assessed patients' visual quality by means of 25, 40, and 80 cm VA tests.
      RESULTS: The best centration results were achieved with the POD Toric FineVision
      model, although the differences were not statistically significant. As for lens
      rotation, it was below 5 degrees  in all cases under study. Regarding VA, all
      subjects attained at least 0.3 logMAR for far distance uncorrected VA, at 80 cm
      VA was about 0.2 logMAR, at 40 cm it was above 0.15 logMAR, and at 25 cm it was
      about 0.3 logMAR for both lens types. CONCLUSION: All three intraocular lens
      models yield excellent visual results at far, near as well as intermediate
      distances. The POD FineVision and POD Toric FineVision models, with double C-loop
      design, yielded the best results centration-wise and rotation-wise. Differences
      had no clinical relevance.

PMID- 30198330
TI  - Influence of Color in a Lactation Room on Users' Affective Impressions and
      Preferences.
AB  - OBJECTIVE: The present study aims to examine the influence of environmental color
      hue in a lactation room at a health center on users' affective response and
      preference. BACKGROUND: Hospital design plays an important role in the emotional
      experience of patients. In this regard, many studies have attempted to find
      relationships between design variables and healthcare facilities users' response.
      Color has been frequently examined because it is always present in the
      environment and can be easily changed. However, most of the studies dealing with
      color-emotion relationships acquire users' affective response by questionnaires
      developed by experts which could lead to inaccurate results since nonexperts may
      misunderstand concepts set by experts and use nonimmersive images to simulate the
      environments to assess. METHODS: To overcome these limitations, a Kansei
      Engineering-based approach was proposed. In the first phase, users' specific
      affective factors for lactation rooms were determined using Semantic
      Differential. In the second phase, the influence of nine different color hues on
      users' affective factors was obtained. An immersive display system was used to
      visualize the room altering hues in an isolated and controlled way. RESULTS: (1)
      Six user's affective factors connected to the lactation rooms were discovered:
      safety, elegance, coziness, spaciousness, simplicity, and luminosity, of which
      coziness has the most impact on the assessment of the room. (2) Warm colors like
      orange and yellow tend to score highly for coziness which puts them in leading
      positions when users' assess lactation rooms. CONCLUSIONS: Results provide
      recommendations for designers and show the advantages of using semantic
      differential and immersive displays to analyze user's affective response to
      environments.

PMID- 30198331
TI  - Performance of a Factory-Calibrated, Real-Time Continuous Glucose Monitoring
      System in Pediatric Participants With Type 1 Diabetes.
AB  - BACKGROUND: The perceived value and consistent use of continuous glucose
      monitoring (CGM) systems depends in part on their accuracy. We assessed the
      performance of a sixth-generation CGM system (Dexcom G6) in children and
      adolescents. METHODS: Forty-nine participants (6-17 years of age, mean +/- SD of
      13.5 +/- 3.3 years), all with type 1 diabetes, enrolled and data were available
      from 37. Each participant wore 1 sensor for up to 10 days and was asked to
      undergo an in-clinic visit lasting 6-12 hours for frequent blood glucose (BG)
      sample testing on one of the sensor wear days. Estimated glucose values (EGVs)
      from the G6 system were compared with venous BG values measured with a laboratory
      reference instrument (YSI). RESULTS: The overall mean absolute relative
      difference (MARD) for 1387 EGV-YSI pairs was 7.7%, and the overall percentage of
      EGVs within 20% or 20 mg/dL of the YSI reference value (for YSI > or ?100 mg/dL,
      respectively, the "%20/20") was 96.2%. The %20/20 was 92.1% on Day 1 and 91.0% on
      Day 10 of sensor wear. For EGVs <70 mg/dL, 92.6% of the YSI values were within 20
      mg/dL and for EGVs >250 mg/dL, 100% of the YSI values were within 20%.
      Differences between EGVs and YSI values in over 99.9% of the pairs posed no or
      only slight clinical risk as evaluated by surveillance error grid analysis.
      CONCLUSIONS: The accuracy of the G6 CGM system in pediatrics may encourage
      consistent use of the system and contribute to improved glycemic outcomes in this
      population.

PMID- 30198332
TI  - Changes in sexual activity of male patients with ankylosing spondylitis
      undergoing total hip arthroplasty.
AB  - INTRODUCTION: Sexual activity is often an important component of life. To date,
      no studies have examined sexual activity before and after total hip arthroplasty
      (THA) in male patients with ankylosing spondylitis (AS). The purpose of the
      current study was to evaluate the effect of THA on sexual activity and to explore
      the most commonly reported and comfortable coital position for male AS patients
      with hip involvement. METHODS: Data from 31 male AS patients who underwent THA
      for hip involvement were retrospectively reviewed. Information from the
      International Index of Erectile Function (IIEF), the Harris Hip Score (HHS) and
      other clinical parameters was collected and monitored over time. We compared the
      above-mentioned parameters before surgery and 2 years after surgery and analysed
      the correlation between changes on the IIEF and changes in clinical parameters.
      RESULTS: The domain and total scores of the IIEF, except EF, were significantly
      higher after surgery than were those before surgery ( p < 0.05). There was a
      significant positive correlation between changes on the IIEF and improvement in
      flexion-extension range of motion (ROM), adduction-abduction ROM and HHS ( p <
      0.05). Most patients (26/31, 83.9%) resumed sexual activity 5-12 weeks after
      surgery. The pre- and postoperative distributions of the most commonly reported
      and comfortable position were not significantly different (p > 0.05).
      CONCLUSIONS: Successful THA may improve sexual activity in male AS patients with
      hip involvement. Changes in hip ROM show the most significant correlation with
      improvement in sexual activity. Resumption of sexual activity occurs within 5-12
      postoperative weeks.

PMID- 30198333
TI  - The effects of explicit instruction in academic vocabulary during shared book
      reading on the receptive vocabulary of children with complex communication needs.
AB  - The purpose of this study was to evaluate the effect of explicit vocabulary
      instruction during shared reading experiences on the acquisition of receptive
      academic vocabulary for children with complex communication needs. A single
      subject, multiple-probe design was used. Three preschool-aged children (i.e., one
      with autism spectrum disorder, one with developmental delay, and one with a rare
      genetic disorder) were each taught two sets of vocabulary words. Intervention
      consisted of explicit vocabulary instruction associated with shared reading of
      academic texts. All three children acquired 10 targeted academic vocabulary items
      receptively and maintained vocabulary knowledge for at least 4 weeks. Data also
      suggest probable generalization to new representations. Additionally,
      participants became more adept at learning via this method, acquiring the second
      vocabulary set in significantly less time. Results indicate that explicit
      vocabulary instruction during shared reading experiences can be effective for
      teaching receptive vocabulary to children with complex communication needs.

PMID- 30198334
TI  - Biogenic synthesis of silver nanoparticles using extracts of Leptolyngbya JSC-1
      that induce apoptosis in HeLa cell line and exterminate pathogenic bacteria.
AB  - Utilizing novel approaches for the green synthesis of metal nanoparticles are of
      great importance. Therefore, we reported biogenic synthesis of silver
      nanoparticles (AgNPs) using extracts of Leptolyngbya strain JSC-1, and their
      significant applications against pathogenic bacteria and cancerous HeLa cell
      line. The biofabricated AgNPs were characterized by UV-visible spectroscopy,
      FTIR, SEM, TEM, DLS and zeta-potential. The as prepared AgNPs were assessed for
      inhibition of bacterial growth and induction of apoptosis in HeLa cells by
      different doses of AgNPs was evaluated. UV-visible spectroscopy and FTIR of AgNPs
      demonstrated the surface plasmon resonance at 413 nm and interaction among
      extract and nanoparticles, respectively. Electron microscopy revealed the
      morphology and DLS demonstrated size distribution of the particles (10-100 nm).
      Zeta potential values were between -47 and 0 mV, indicating stability of the
      particles. Proliferation of HeLa cells was significantly inhibited and severe
      cytotoxicity with higher intracellular uptake were observed after applying high
      concentration of AgNPs. Efficient inhibition zones (17 +/- 2 and 21 +/- 2 mm)
      were produced at maximum concentration (100 ul from 1 mg ml-1 stock of AgNPs) for
      Staphylococcus aureus and Escherichia coli, respectively. These findings reveal
      that the biofabricated AgNPs possess strong antibacterial activity and ability to
      induce apoptosis in cancer cell line (HeLa).

PMID- 30198335
TI  - Thoughts on Chemistry, Manufacturing and Control of Cell Therapy Products for
      Clinical Application.
AB  - Cell therapy has emerged as a promising new treatment in medicine, which is
      expected to be able to cure diseases by repairing, replacing, and regenerating
      tissues, as well as immune-modulation. However, challenges remain in ensuring
      consistent quality, clinical efficacy and safety profiles because of the
      diversity of cell types and clinical indications for cell therapy products
      (CTPs), as well as different and complex manufacturing process. Therefore,
      scientific consensus and regulatory measurements are urgently warranted to
      promote the translation of the latest scientific advances and innovative
      manufacturing technologies into clinical application. This article aims to
      propose perspectives on the manufacturing, quality study and quality control of
      CTPs and provide considerations and opinions in the regulation of CTPs.

PMID- 30198336
TI  - Adipoinductive effect of extracellular matrix involves cytoskeleton changes and
      SIRT1 activity in adipose tissue stem/stromal cells.
AB  - Adipose tissue (AT) homeostasis and expansion are dependent on complex crosstalk
      between resident adipose stromal/stem cells (ASCs) and AT extracellular matrix
      (ECM). Although adipose tissue ECM (atECM) is one of the key players in the stem
      cell niche, data on bidirectional interaction of ASCs and atECM are still scarce.
      Here, we investigated how atECM guides ASCs' differentiation. atECM altered shape
      and cytoskeleton organization of ASCs without changing their proliferation, beta
      galactosidase activity and adhesion. Cytoskeleton modifications occurred due to
      fostered parallel organization of F-actin and elevated expression of Vimentin in
      ASCs. After seven-day cultivation, atECM impaired osteogenesis of ASCs,
      simultaneously decreasing expression of Runx2. In addition, atECM accelerated
      early adipogenesis concomitantly with altered Vimentin organization in ASCs,
      slightly increasing PPARgamma, while elevated Adiponectin and Vimentin mRNA
      expression. Early adipogenesis triggered by atECM was followed by upregulated
      mitochondrial activity and Sirtuin 1 (SIRT1) expression in ASCs. Proadipogenic
      events induced by atECM were mediated by SIRT1, indicating the supportive role of
      atECM in adipogenesis-related metabolic state of ASCs. These results provide a
      closer look at the effects of atECM on ASC physiology and may support the
      advancement of engineering design in soft tissue reconstruction and fundamental
      research of AT.

PMID- 30198337
TI  - MAPPs for the identification of immunogenic hotspots of biotherapeutics; an
      overview of the technology and its application to the biopharmaceutical arena.
AB  - INTRODUCTION: Anti-drug antibody (ADA) responses are becoming an increasing
      concern as more highly engineered and sophisticated biotherapeutics enter the
      clinic. An arsenal of tools has been developed to identify potential T cell
      epitopes that may drive unwanted immunological responses to protein therapeutics;
      one such tool is termed 'Major Histocompatibility Complex-Associated Peptide
      Proteomics' (MAPPs). This review highlights the evolution of this MHC II
      profiling technology, its technological advantages and limitations, and its
      utility in helping to de-risk the immunogenicity of biotherapeutics. Areas
      covered: A comprehensive literature review was performed along with discussions
      with key leaders in the field of MAPPs to summarize the importance of monitoring
      potential immunogenicity of clinical molecules. Herein we also describe how MAPPs
      has been applied specifically for monitoring MHC II peptides derived from
      biotherapeutics. Expert commentary: Given the importance of this growing field we
      discuss the complementary tools used in conjunction with MAPPs and review case
      studies where this approach has informed clinical studies and in some cases
      allowed re-engineering of the biotherapeutic moiety to a less immunogenic format.

PMID- 30198338
TI  - MRI tracking of polyethylene glycol-coated superparamagnetic iron oxide-labelled
      placenta-derived mesenchymal stem cells toward glioblastoma stem-like cells in a
      mouse model.
AB  - Mesenchymal stem cells (MSCs) that display homing and infiltration properties
      towards tumor cells are a promising cellular targeting vector for brain tumor
      therapy but are limited to local-regional delivery in current preclinical models.
      Here, we investigated whether placenta-derived MSCs (P-MSCs) are a superior
      cellular vector for systemic targeting of glioblastoma stem-like cells (GSCs),
      with an imaging modality to real-time monitor the trafficking P-MSCs to
      glioblastoma sites. Results demonstrated that P-MSCs had greater migratory
      activity towards GSCs and across blood-brain barrier compared with bone marrow
      derived MSCs, and this activity was enhanced by hypoxia precondition. Chemokine
      ligand 5 was identified as a chemoattractant responsible for the glioblastoma
      tropism of P-MSCs. Polyethylene glycol-coated superparamagnetic iron oxide (PEG
      SPIO) was synthesized for cellular labelling and imaging P-MSCs, displaying high
      cellular uptake and no cytotoxic effect on P-MSCs cell proliferation or stemness
      property. The homing effects of intravenously administered PEG-SPIO-labelled P
      MSCs towards intracerebral GSCs were able to be detected in mice models through
      T2-weighted magnetic resonance imaging (MRI). This study suggests the possibility
      of innovative systemic P-MSC-based cell therapy for aggressive GSCs, developing a
      state-of-the-art theranostic technique for real-time tracking of therapeutic P
      MSCs tumor infiltration through cellular MRI.

PMID- 30198339
TI  - Gene Therapy for Sickle Cell Disease: A Lentiviral Vector Comparison Study.
AB  - Sickle cell disease (SCD) is an inherited blood disorder caused by a single amino
      acid substitution in the beta-globin chain of hemoglobin. Gene therapy is a
      promising therapeutic alternative, particularly in patients lacking an allogeneic
      bone marrow (BM) donor. One of the major challenges for an effective gene therapy
      approach is the design of an efficient vector that combines high-level and long
      term beta-globin expression with high infectivity in primary CD34+ cells. Two
      lentiviral vectors carrying an anti-sickling beta-globin transgene (AS3) were
      directly compared: the Lenti/betaAS3-FB, and Globe-AS3 with and without the FB
      insulator. The comparison was performed initially in human BM CD34+ cells derived
      from SCD patients in an in vitro model of erythroid differentiation.
      Additionally, the comparison was carried out in two in vivo models: First, an NOD
      SCID gamma mouse model was used to compare transduction efficiency and beta
      globin expression in human BM CD34+ cells after transplant. Second, a sickle
      mouse model was used to analyze beta-globin expression produced from the vectors
      tested, as well as hematologic correction of the sickle phenotype. While minor
      differences were found in the vectors in the in vitro study (2.4-fold higher
      vector copy number in CD34+ cells when using Globe-AS3), no differences were
      noted in the overall correction of the SCD phenotype in the in vivo mouse model.
      This study provides a comprehensive in vitro and in vivo analysis of two globin
      lentiviral vectors, which is useful for determining the optimal candidate for SCD
      gene therapy.

PMID- 30198340
TI  - Rituximab (anti-CD20)-modified AZD-2014-encapsulated nanoparticles killing of B
      lymphoma cells.
AB  - The mTOR signal pathway is often highly activated in B-cell non-Hodgkin's
      lymphoma (NHL) and promotes cancer progression and chemo-resistance. Therefore,
      the pathways of mTOR are an important target for drug development in this
      disease. In the current study, we developed a rituximab (anti-CD20)-modified mTOR
      inhibitor, AZD-2014, loaded into nanoparticles (Ab-NPs-AZD-2014) for trial of its
      anti-NHL effect. In a cultured NHL cell line, Ab-NPs-AZD-2014 inhibited cancer
      cell growth, induced cell apoptosis, and blocked activation of mTORC1 and mTORC2
      in Raji cells. These results indicate that antibody modification and nanomaterial
      loading of AZD-2014 with anti-CD20 significantly improved efficacy of AZD-2014
      against NHL cells. This approach may ultimately deserve testing in therapy
      against NHL.

PMID- 30198341
TI  - Global trends in research and commercialization of exogenous and endogenous RNAi
      technologies for crops.
AB  - It has only been about 20 years since the first Nobel Prize-winning work on RNA
      interference (RNAi) in Caenorhabditis elegans was published in the journal
      Nature. Fast forward to today, and the use of RNA molecules as gene-silencing
      elements in crops has helped scientists to unveil possible solutions to the
      global problems of agricultural losses due to pests, viruses, pathogens, and to
      other abiotic and biotic stresses. The recent proliferation of publications
      suggests that the technology has gained significant attention and received ample
      funding support. In this article, an attempt has been made to visualize recent
      trends in Research & Development (R&D) investment in this field by analyzing top
      cited scholarly articles, patent trends, and commercialization activity. The
      publication and citation analysis identified that the development of RNAi-based
      crops conferring resistance against viruses, fungi, and pests are at the
      forefront of RNAi research and that Chinese and US institutions are the leaders
      in this field. The patent landscape analysis for RNAi technology over all aspects
      related to RNAi-derived crops provides an overview of patenting activity from a
      geographical, organizational, and legal perspective. Such an exercise is pivotal
      to industry players and public institutions aiming at creating intellectual
      property that is commercially appealing. An upswing in commercial interests in
      this technology in recent years is reflected by a consistent number of patent
      filings in US, European, and Chinese patent offices, with multinational giant
      firms as the most prolific patent filers. The expanding RNAi commercialization
      landscape is supported by a series of strategic partnerships, licensing
      agreements, and acquisitions created between agribusinesses, public research
      institutions, and startup companies. From key observations, we would like to
      highlight that such investments have very positive impacts on the development of
      RNAi technology. Nonetheless, the success of this technology is dependent on
      several factors, such as financial requirements, the complexity, and timeframe of
      the entire development process, as well as stringent regulations imposed by the
      relevant authorities. In most countries, RNAi-based transgenic crops are still
      considered as a genetically modified (GM) product, which necessitates the crops
      to undergo rigorous evaluation before approval is granted. Recent advancements in
      exogenous RNAi-derived biopesticides have provided a nontransgenic alternative to
      GM crops. However, challenges still remain in the form of technical hurdles and
      regulatory ambiguities surrounding this emerging technology. Its full potential
      remains to be realized.

PMID- 30198342
TI  - Bioremediation through microbes: systems biology and metabolic engineering
      approach.
AB  - Today, environmental pollution is a serious problem, and bioremediation can play
      an important role in cleaning contaminated sites. Remediation strategies, such as
      chemical and physical approaches, are not enough to mitigate pollution problems
      because of the continuous generation of novel recalcitrant pollutants due to
      anthropogenic activities. Bioremediation using microbes is an eco-friendly and
      socially acceptable alternative to conventional remediation approaches. Many
      microbes with a bioremediation potential have been isolated and characterized
      but, in many cases, cannot completely degrade the targeted pollutant or are
      ineffective in situations with mixed wastes. This review envisages advances in
      systems biology (SB), which enables the analysis of microbial behavior at a
      community level under different environmental stresses. By applying a SB
      approach, crucial preliminary information can be obtained for metabolic
      engineering (ME) of microbes for their enhanced bioremediation capabilities. This
      review also highlights the integrated SB and ME tools and techniques for
      bioremediation purposes.

PMID- 30198343
TI  - The effect of preconceptional exposure of F0 male mice to di(2
      ethylhexyl)phthalate on the induction of reproductive toxicity in F2 generation.
AB  - The aim of the study was the estimation of the effects of 8 weeks exposure mature
      and pubescent male mice to DEHP on the prenatal development of the offspring F2
      generation. The F1 offspring, of males exposed for whole cycle of spermatogenesis
      to DEHP (2000 mg/kg bw or 8000 mg/kg bw) and unexposed females, at 8-9 weeks of
      age were caged males with females from the same group, but from different litter.
      Eight weeks preconceptional exposure of mature F0 males to 2000 mg/kg bw DEHP
      induced the significantly higher number of dead fetuses in the F2 offspring;
      however, the effect on the sperm count and quality of F1 males was not seen.
      Contrary, after such exposure of pubescent males not significantly decrease in
      the number of live implants was noted. Results showed that the subchronical,
      preconceptional exposure of F0 males to DEHP did not influence strongly on the F2
      generation of the offspring. Our study did not confirm higher sensitivity germ
      cells of pubescent males to harmful effects induced by DEHP. The developmental
      effect was present as the enhanced number of dead implants of F2 generation after
      exposure of mature F0 males and slight reduction in the number of live fetuses
      following the exposure of immature males. It may confirm ability to male mediated
      developmental toxicity.

PMID- 30198344
TI  - Innovative prediction models for spine pain.

PMID- 30198345
TI  - The association between early life antibiotic use and allergic disease in young
      children: recent insights and their implications.
AB  - INTRODUCTION: Greater prescribing of antibiotics to infants has coincided with an
      epidemic of allergic disease. Through meta-analytic synthesis, accumulating
      evidence from prospective or database cohorts suggests a link between infant
      antibiotic treatment and the development of atopy. Stronger associations seen
      with multiple course and broad-spectrum antibiotic treatment add to biological
      plausibility. A major bias, confounding by indication, has been addressed in
      studies on antibiotic treatment of conditions which do not precede allergic
      disease. Areas covered: Our review provides an up-to-date synthesis of the
      current literature on associations between infant antibiotic exposure and future
      allergic disease. We discuss methods that assist in reducing study bias and look
      at new insights from studies of the infant gut microbiome. Expert commentary:
      Large-scale profiling of the gut microbiome provides a new tool for disentangling
      biases found in observational studies of infant antibiotic use. To date,
      microbial dysbiosis of the infant gut has been reported to predict allergic
      disease independent of antibiotic exposure up to 3 months after birth. However,
      these studies have not accounted for antibiotic treatment in later infancy.
      Continued study of the infant gut microbiome, mycobiome, or resistome will
      provide a closer link to antibiotic treatment or refute it as a cause of allergic
      disease.

PMID- 30198346
TI  - Algal polysaccharides: potential bioactive substances for cosmeceutical
      applications.
AB  - The cosmetics industry is one of the most profitable in the world today. This
      multi-billion-dollar industry has a profound sociological impact worldwide. Its
      influence is global, with most individuals being concerned with conserving their
      physical appearance, beauty, and youth. The consumers' desire for novel, better,
      and safer products has stimulated the utilization of natural-product-based
      cosmeceutical formulations over synthetic chemicals. With remarkable advancements
      in marine bioresource technology, algal polysaccharides have gained much
      attention as bioactive ingredients in cosmeceuticals. Algae biosynthesize a
      variety of polysaccharides including fucoidans, alginates, carrageenans,
      galactans, agar, porphyran, glucans, and ulvans, all of which exhibit distinctive
      structural and functional properties. Many of these materials have been proven to
      possess skin-protective effects, including anti-wrinkle, lightening,
      moisturizing, UV protective, antioxidative, and anti-inflammatory activity.
      Moreover, they have a wide spectrum of physicochemical properties, such as the
      ability to form hydrogels, which extend their utilization as emulsifiers,
      stabilizers, and viscosity controlling ingredients in cosmeceuticals.
      Accordingly, algal hydrocolloids and their synthetic derivatives can also be
      applied in tissue engineering and cosmetic surgery. The challenge is to increase
      awareness about these polysaccharides and consequently generate value-added
      products. This review discusses the beneficial biological and physicochemical
      properties of algal polysaccharides, highlighting their potential in
      cosmeceutical applications.

PMID- 30198347
TI  - When are the cardiovascular and stroke risks too high? Pharmacotherapy for stroke
      prophylaxis.
AB  - INTRODUCTION: Stroke is a significant source of morbidity and mortality in
      developed countries. Cardioembolic strokes represent approximately 15-30% of all
      ischemic strokes. They are frequently related to atrial fibrillation (AF) and
      have a worse prognosis and high recurrence rates when compared to other causes
      (e.g. atherosclerosis). Areas covered: This review includes a summary of general
      and specific scores to assess cardiovascular and stroke risks, with a focus on
      specific scores available in AF. Recommendations for antithrombotic therapy are
      also reviewed. Expert opinion: Several scores are available for the evaluation of
      stroke risk. They are useful to identify the risk factors that trigger the need
      for medical interventions. Integrated risk scores with visual interfaces showing
      the risk of events, with and without the proposed interventions, can aid decision
      making. The risk of stroke can definitely be considered too high in those
      patients with a history of stroke/transient ischemic attack, who need
      antiplatelet therapy (after a non-cardioembolic stroke) or anticoagulant therapy
      (after a cardioembolic stroke). For primary prevention of stroke, antiplatelet
      therapy is not usually recommended, while anticoagulation should be considered if
      the patient has concomitant AF and at least one additional risk factor unrelated
      to sex.

PMID- 30198349
TI  - Corrigendum.

PMID- 30198348
TI  - Recent developments in colorimetric immunoassays using nanozymes and plasmonic
      nanoparticles.
AB  - Enzyme-linked immunosorbent assay (ELISA) is a popular detection technique for
      the screening and diagnosis of diseases. The sensitivity of ELISA can be
      increased by the incorporation of nanoparticles. Through this article, we discuss
      the utilization of nanoparticles in ELISA. Nanoparticles possess an intrinsic
      biological peroxidase-like activity which allows it to act as an enzyme mimic for
      the development of an improved analysis method. Different nanoparticles (gold
      nanoparticles, silver nanoparticles, etc.) carry different peroxidase-mimic
      characteristics. Besides this, nanoparticles can also perform as a colorimetric
      substrate in ELISA where it gives a more prominent color change compared to the
      commonly used colorimetric substrate TMB. This article also focuses on the
      mechanisms behind this color change including aggregation, in situ nanoparticle
      growth, seeding, and etching.

PMID- 30198350
TI  - Risks associated with lung transplantation in cystic fibrosis patients.
AB  - INTRODUCTION: Survival after lung transplantation lags behind outcomes of other
      solid organ transplants, and complications from lung transplant are the second
      most common cause of death in cystic fibrosis. Evolving surgical techniques,
      therapeutics, and perioperative management have improved short-term survival
      after lung transplantation, yet have not translated into significant improvement
      in long-term mortality. Areas covered: We review risk factors for poor long-term
      outcomes among patients with cystic fibrosis undergoing lung transplantation to
      highlight areas for improvement. This includes reasons for organ dysfunction,
      complications of immunosuppression, further exacerbation of extrapulmonary
      complications of cystic fibrosis, and quality of life. A literature search was
      performed using PubMed-indexed journals. Expert commentary: There are multiple
      medical and socioeconomic barriers that threaten long-term survival following
      lung transplant for patients with cystic fibrosis. An understanding of the causes
      of each could elucidate treatment options. There is a lack of prospective,
      multicenter, randomized control trials due to cost, complexity, and feasibility.
      Ongoing prospective studies should be reserved for the most promising
      interventions identified in retrospective studies in order to improve long-term
      outcomes.

PMID- 30198351
TI  - Intraobserver and interobserver variability in first-trimester transvaginal
      ultrasound cervical length.
AB  - OBJECTIVES: To determine intraobserver and interobserver variability in the
      measurement of different cervical length (CL) components at the first trimester
      (endocervical canal and isthmus), describe the optimum measurement method (single
      line or two lines) and establish a normality curve of first trimester CL in our
      population. METHODS: Women who attended the first-trimester US scan, between 11.0
      and 13.6 weeks of gestation at Vall d'Hebron Universitary Hospital, Barcelona,
      Spain were included. Inclusion criteria were singleton pregnancies in women over
      18 years of age, no gestational complications, uterine malformations or uterine
      surgery. Lengths of the endocervical canal and uterine isthmus were measured
      using two methods. RESULTS: Both methods for endocervical canal measurement,
      single line and two lines, showed low intraobserver variability between
      examiners, with no statistical differences in the majority of measurements. A
      correct correlation existed between examiners using the single-line two-line
      measurements, with a concordance correlation coefficient of 0.76. CONCLUSIONS:
      Cervical length in the first trimester was reproducible for the same physician
      and between different physicians; however, it is essential to ensure examiners
      receive adequate training in the technique.

PMID- 30198352
TI  - Older People Living Well Beyond Cancer: The Relationship Between Emotional
      Support and Quality of Life.
AB  - OBJECTIVE: To investigate the influence of emotional support on the quality of
      life (QoL) of older cancer survivors. METHOD: We use data from the English
      Longitudinal Study of Ageing to assess the relationship between perceived
      emotional support and QoL, comparing people who were cancer survivors ( n = 533)
      to people without cancer ( n = 8,203). RESULTS: Most people reported high
      emotional support and had good QoL ( M = 42.57, scale = 0-57). However, linear
      regression modeling showed cancer survivors had on average slightly lower QoL (
      2.10 SE = 0.82). Those who reported having low support reported much poorer QoL;
      this relationship was similar for both cancer survivors and people without
      cancer. DISCUSSION: The impact of low emotional support on QoL compounds with the
      independent detrimental effect of being a cancer survivor. Interventions that
      increase emotional support are likely to improve QoL for cancer survivors.

PMID- 30198353
TI  - Genetic aspects of idiopathic asthenozoospermia as a cause of male infertility.
AB  - Infertility is a worldwide problem affecting about 15% of couples trying to
      conceive. Asthenozoospermia (AZS) is one of the major causes of male infertility,
      diagnosed by reduced sperm motility, and has no effective therapeutic treatment.
      To date, a few genes have been found to be associated with AZS in humans and
      mice, but in most of cases its molecular aetiology remains unknown. Genetic
      causes of AZS may include chromosomal abnormalities, specific mutations of
      nuclear and mitochondrial genes. However recently, epigenetic factors, altered
      microRNAs expression signature, and proteomics have shed light on the
      pathophysiological basis of AZS. This review article summarises the reported
      genetic causes of AZS.

PMID- 30198355
TI  - Viral infections in the biologic therapy era.
AB  - INTRODUCTION: The development of biologic therapies for treating patients with
      rheumatic, hematologic, or oncological diseases has increased in the last few
      years, spreading their use in clinical practice. Areas covered: Clinical
      experience has evidenced substantial risks for some viral infections and/or
      reactivations such as viral hepatitis, herpetic infections, and other viruses, as
      a consequence of specific immune pathway blockages. Biological therapies produce
      a variable risk of reactivation of viral infections, which is particularly
      uncertain in the case of the most recently introduced agents. Here we make an
      extensive review of the viral infections associated with the use of biological
      drugs and provide a series of recommendations for its prevention and management.
      Expert commentary: To prevent these infections/reactivations, the practitioner
      must be aware of the infection-risk profile, performing accurate screening during
      and after the use of any biologic agent. In some instances, expert
      recommendations are made for some therapies, while in other scenarios
      recommendations have not yet been defined making experimental and clinical
      research an essential approach to elucidate multiple issues yet not resolved in
      this field.

PMID- 30198354
TI  - Appetite during the second and third trimesters mediates the impact of prenatal
      environmental tobacco smoke exposure on symmetric full-term low birth weight.
AB  - OBJECTIVE: To examine the relationship of prenatal environmental tobacco smoke
      (ETS) exposure and full-term low birth weight (FT-LBW) when taking anthropometric
      proportionality into consideration, and explore whether appetite mediates their
      association. STUDY DESIGN: We conducted a case-control study among pregnant women
      at two Women and Children's Hospitals in Guangdong, China. Information was
      collected through interview and medical records review. A series of logistic and
      linear regressions were used to examine the relationships of prenatal ETS
      exposure, appetite, and FT-LBW. RESULTS: After adjusting for the potential
      confounders, prenatal ETS exposure was significantly negatively associated with
      FT-LBW (OR: 1.83, 95%CI: 1.35-2.48) and negatively correlated with maternal
      appetite in second and third trimester during pregnancy (beta: -0.11, standard
      error: 0.03). Moreover, mediation analysis illustrated that maternal appetite
      partially mediated 12.00% of their relationship. However, subgroup analysis
      showed that prenatal ETS exposure was linked to higher risk of symmetric FT-LBW
      (OR: 2.26, 95%CI: 1.56-3.26) but not asymmetric FT-LBW. And maternal appetite
      explained only 6.45% of their relationship. CONCLUSIONS: Maternal prenatal ETS
      exposure increased risk of having symmetric FT-LBW infant, and appetite might
      mediate their relationship partially. This study emphasizes the importance of
      sample homogeneity and stresses the needs to improve the public awareness of the
      harmful effects of ETS.

PMID- 30198356
TI  - Factors associated with misdiagnosis of frozen section of mucinous borderline
      ovarian tumor.
AB  - Objective This study was performed to investigate the diagnostic accuracy of
      frozen section (FS) of mucinous borderline ovarian tumors (mBOTs) and the
      diagnostic value of various risk factors for misdiagnosis. Methods Patients with
      either an FS or permanent pathologic diagnosis of mBOT were included. Optimum cut
      off values for serum tumor markers and maximal tumor diameter were determined,
      and risk factors for underdiagnosis of mucinous malignant ovarian tumors (mMOTs)
      were evaluated. The sensitivity, specificity, Youden's index, and diagnostic odds
      ratio of the risk factors were assessed to determine their diagnostic value for
      mMOTs. Results Of 121 included patients, 97 were diagnosed with mBOTs by FS.
      Relatively abnormal cancer antigen 125 (CA125), carbohydrate antigen 19-9 (CA19
      9), and carcinoembryonic antigen (CEA) levels; bilateral tumors; and specific
      pathological features showed significant associations with underdiagnosis of
      mMOTs in the univariate analysis. The presence of specific pathological features
      was the only significant risk factor in the multivariate analysis. The CA125,
      CA19-9, and CEA levels and specific pathological features demonstrated certain
      diagnostic value in detecting malignant cases among FS-diagnosed mBOTs.
      Conclusions In patients with FS-diagnosed mBOT, significant predictors of
      malignancy were relatively higher CA125, CA19-9, and CEA levels; bilateral
      tumors; and tumors with specific pathological features.

PMID- 30198357
TI  - Preventing central nervous system metastases in non-small cell lung cancer.
AB  - INTRODUCTION: There are no effective central nervous system (CNS) metastases
      prevention methods in lung cancer patients. Prophylactic cranial irradiation has
      a limited effectiveness and relatively high toxicity. Systemic chemotherapy is
      not relevant in reducing the risk of CNS in lung cancer patients. The
      understanding of molecular background of brain metastases in non-small cell lung
      cancer (NSCLC) patients could contribute to the development of personalized
      treatments for such patients. Areas covered: This article summarizes the latest
      clinical trials concerning the use of radiotherapy, chemotherapy, molecularly
      targeted therapies, and immunotherapy in lung cancer patients, with particular
      consideration of brain lung cancer metastasis prevention. The literature search
      was undertaken via PubMed and EMBASE searches and relevant articles are included
      in this review. Expert commentary: The recent data supports that EGFR-TKIs and
      ALK inhibitors are clinically relevant for first-line treatment to prevent and
      treat CNS metastases in molecularly selected NSCLC patients. In the future, high
      hopes for the prevention of CNS metastases in NSCLC patients are associated with
      immunotherapy concerning immune check-points inhibitors.

PMID- 30198358
TI  - Predictors of tuberculosis treatment success under the DOTS program in Namibia.
AB  - OBJECTIVES: Optimal treatment success rates are critical to end tuberculosis in
      Namibia. Despite the scale-up of high quality directly observed therapy short
      course strategy (DOTS) in Namibia, treatment success falls short of the global
      target of 90%. The objective of this study was to ascertain the predictors of
      treatment success rates under DOTS in Namibia to provide future direction.
      METHODS: A nation-wide comparative analysis of predictors of treatment success
      was undertaken. Tuberculosis cases in the electronic tuberculosis register were
      retrospectively reviewed over a 10-year period, 2004-2016. The patient,
      programmatic, clinical, and treatment predictors of treatment success were
      determined by multivariate logistic regression modeling using R software.
      RESULTS: 104,603 TB cases were registered at 300 DOTS sites in 37 districts. The
      10-year period treatment success rate was 80%, and varied by region (77.2%
      89.2%). The patient's sex and age were not significant predictors. The
      independent predictors for treatment success as were: Region of DOTS
      implementation (p=0.001), type of directly observed treatment (DOT) supporter
      (p<0.001), sputum conversion at 2 months (p=0.013), DOT regimen (p<0.001),
      cotrimoxazole prophylaxis (p=0.002), and HIV co-infection (p=0.001). CONCLUSION:
      Targeted programmatic, clinical and treatment interventions are required to
      enhance DOTS treatment success in Namibia. These are now ongoing.

PMID- 30198360
TI  - Investigation of Dose-Response Relationships for Effects of White Light Exposure
      on Correlates of Alertness and Executive Control during Regular Daytime Working
      Hours.
AB  - To date, it is largely unknown which light settings define the optimum to steer
      alertness and cognitive control during regular daytime working hours. In the
      current article, we used a multimeasure approach combined with a relatively large
      sample size ( N = 60) and a large range of intensity levels (20-2000 lux at eye
      level) to investigate the dose-dependent relationship between light and
      correlates of alertness and executive control during regular working hours in the
      morning and afternoon. Each participant was exposed to a single-intensity light
      level for 1 h after a 30-min baseline phase (100 lux at the eye) in the morning
      and afternoon (on separate days) during their daily routine. Results revealed no
      clear dose-dependent relationships between 1-h daytime light exposure and
      correlates of alertness or executive control. Subjective correlates showed only
      very modest linear relationships with the log-transformed illuminance, and we
      found no significant effects of light intensity on the behavioral and
      physiological indicators. Overall, these results suggest that daytime exposure to
      more intense light, at least for 1 h of exposure, may not systematically benefit
      alertness or executive functioning. However, future research is required to
      investigate effects of longer exposure durations and potential moderations by
      prior light exposure, personal characteristics, and spectrum.

PMID- 30198359
TI  - Effects of propofol and isoflurane on excitatory amino acid carrier 1 mRNA and
      glutathione protein levels in rat hippocampus.
AB  - OBJECTIVE: We compared the effects of two anesthetics, isoflurane and propofol,
      on the nuclear or cytosolic localization of nuclear factor erythroid 2-related
      factor 2 (Nrf2), mRNA expression levels of excitatory amino acid carrier 1
      (EAAC1), and glutathione (GSH) protein levels in the rat hippocampus. METHODS:
      Fifty-two adult male Sprague-Dawley rats were randomly divided into three groups:
      a control group, a group that received propofol for 240 minutes (P240), and a
      group that received isoflurane for 240 minutes (I240). We compared GSH protein
      and EAAC1 mRNA expression levels in the rat hippocampus and evaluated Nrf2
      content in cytosolic and nuclear fractions in the three groups. RESULTS: GSH
      protein and EAAC1 mRNA expression levels were significantly higher in the I240
      and P240 groups compared with the control group. The I240 and P240 groups showed
      lower Nrf2 protein levels in the cytosolic fractions, but higher levels in the
      nuclear fractions compared with the control group. CONCLUSION: Treatment with
      isoflurane or propofol may enhance GSH production by facilitating translocation
      of Nrf2 into the nucleus and increasing EAAC1mRNA expression in the rat
      hippocampus. Isoflurane and propofol show similar profiles in EAAC1 expression
      associated GSH production.

PMID- 30198361
TI  - The need for school administrative policies to manage meningitis amongst students
      in Nigeria: a viewpoint.
AB  - Students are at greater risk of meningitis than non-students of similar age.
      However, a lack of specific school administrative policies for the management of
      meningitis may contribute to the increasing incidence of meningitis in the
      student population. The study aims were to promote the need for a policy
      framework in school settings to manage meningitis, and to encourage research to
      assess the readiness of school administrators to adopt such a policy in Nigeria.
      The material reviewed here derives from expert opinion, gray literature, national
      data sources, websites, and peer-reviewed journals. It is important to offer
      comprehensible, reliable, and accurate information about meningitis to students
      and staff of every school in Nigeria, as one of the best ways of achieving the
      goal of preventing meningitis in students may be through the adoption and
      implementation of meningitis policy frameworks by school administrators.
      Furthermore, studies are required to examine the readiness of school
      administrators to adopt a meningitis policy framework.

PMID- 30198362
TI  - Characteristics of Female Youth Offenders in New Zealand.
AB  - Female youth offending is poorly understood, despite increased rates of such
      offending. Research indicates there are a range of factors that have a causal
      impact on the development of offending in young people. This study investigated
      risk factors using a retrospective file audit of 184 female youth offenders in
      New Zealand. The findings were classified using Bronfenbrenner's ecological
      model, which highlights the different contextual levels that influence behavior,
      including individual, family, peer, school, community, and cultural factors. The
      results indicate that there are significant risk factors for female youth
      offenders. There were high rates of mental health difficulties, drug use,
      histories of maltreatment, family stressors, peer issues, and school behavior
      problems in the cohort. There was very little difference between violent and
      nonviolent offenders. All the young women had risk factors affecting them at many
      levels. Targeted, multisystemic intervention and prevention programs are
      therefore needed to address female youth offending.

PMID- 30198363
TI  - Orthotropic Liver Transplantation for Acute Intrahepatic Cholestasis in Sickle
      Cell Disease: Clinical and Histopathologic Features of a Rare Case.
AB  - Sickle cell disease has a wide range of hepatic manifestations, with acute
      intrahepatic cholestasis being one of the rarest and most fatal, often resulting
      in acute fulminant hepatic failure. Liver transplantation is an emerging but
      rarely utilized treatment for hepatic failure in the setting of sickle cell
      disease. Few such cases have been reported in the literature, with little
      emphasis on histopathologic correlation. We report a case of acute intrahepatic
      cholestasis in a patient with sickle cell disease who underwent orthotropic liver
      transplantation and describe novel correlating histopathologic features. The
      patient is a 29-year-old man who presented with hyperbilirubinemia, acute kidney
      injury, and coagulopathy. He was diagnosed clinically with acute intrahepatic
      cholestasis and received an orthotropic liver transplant. The explanted liver
      demonstrated marked sinusoidal expansion by sickled erythrocytes, hyperplastic
      Kupffer cells, and extramedullary hematopoiesis. There was extensive sinusoidal
      and centrizonal fibrosis with occlusion of central veins reminiscent of chronic
      sinusoidal obstructive syndrome, a previously undescribed pattern of injury. This
      case represents one of the few reported cases of sickle cell intrahepatic
      cholestasis treated by transplantation and demonstrates the rarely reported
      histopathologic features and gives insight to a potentially new mechanism of
      injury in these patients. Familiarity with the morphologic features of sickle
      cell hepatopathy and its clinical manifestations is important as transplantation
      in sickle cell-related liver injury increases in frequency.

PMID- 30198364
TI  - Persistent feeding difficulties among infants with fetal opioid exposure:
      mechanisms and clinical reasoning.
AB  - AIMS: Infants with fetal exposure to opioids have varying pattern of feeding
      difficulties mainly manifesting as difficulties with aerodigestive adaptation and
      disruptive feeding behavior. The reasons are unclear; in a pilot study, we
      determined basal and adaptive pharyngo-esophageal motility in a group of infants
      with fetal exposure to opioids and persistent feeding difficulties impeding their
      discharge. METHODS: Six infants with fetal opioid exposure compared to 12
      controls who underwent basal and adaptive pharyngo-esophageal manometry to
      characterize the basis for their symptoms. Spontaneous swallows (N = 180) and
      pharyngeal stimuli (N = 113)-induced swallowing responses were analyzed. RESULTS:
      Resting upper esophageal sphincter (UES) pressure was similar in both the groups,
      but resting lower esophageal sphincter (LES) pressure was significantly high and
      it relaxed slowly and inadequately in opioid-exposed infants (p < .05). Upon
      pharyngeal provocation, opioid-exposed infants had higher LES nadir pressure,
      increased duration of esophageal body contraction at proximal-, mid-, and distal
      esophagus, as well as greater area under the curve with distal esophageal
      waveforms, compared to controls (all p < .05). CONCLUSIONS: These pilot
      observations are suggestive of up-regulation of central vagal effects with
      heightened cholinergic excitatory responses and inadequate relaxation responses
      at the foregut, and may form the basis for persistent feeding difficulties in
      opioid-exposed infants. Abnormality with both sensory and motor aspects of vagal
      reflexes may be contributory.

PMID- 30198365
TI  - The effect of colorectal cancer screening on health status in a survey study.
AB  - BACKGROUND: Colorectal cancer (CRC) screening has been found to reduce mortality
      from CRC but it may have adverse effects on other aspects of health. Our aim was
      to evaluate the effect of CRC screening on overall health status among men and
      women within a randomized health-services study in Finland. MATERIAL AND METHODS:
      A random sample of 10,648 men and women born in 1951 received a questionnaire on
      health and lifestyle. They were randomized for CRC screening or controls (1:1) in
      2011 (N = 10,271). The current study population consisted of those who responded
      to the questionnaire both before and after screening (n = 4895). Self-rated
      health (SRH), perceived healthiness of diet and perceived physical fitness were
      used to determine health status, and assessed with logistic and ordered logistic
      models using calendar time (2010, 2012), screening randomization and demographic
      characteristics as covariates. RESULTS: SRH, healthiness of diet and physical
      fitness improved over time (OR 1.32, CI 1.17-1.48, OR 1.23, CI 1.08-1.41 and OR
      1.44, CI 1.28-1.60, respectively). Compared to non-invited controls, CRC
      screening invitation had no effect on these measures (OR 0.91, CI 0.74-1.12, OR
      0.95, CI 0.75-1.20, and OR 1.09, CI 0.87-1.37, respectively). Women reported
      better health status than men. However, among those who attended screening, women
      reported weaker, and men better health status than the respective controls.
      CONCLUSIONS: CRC screening did not have any effect on health status measured
      using self-rated health, healthiness of diet, and physical fitness. Thus,
      screening for colorectal cancer can be recommended as a health policy.

PMID- 30198367
TI  - Can a linear external fixator stand as a surgical alternative to open reduction
      in treating a high-grade supracondylar humerus fracture?
AB  - Objective High-grade pediatric supracondylar humerus fractures are commonly
      treated with closed reduction and internal fixation with percutaneous pinning.
      When this fails, open reduction followed by internal fixation is the widely
      accepted procedure of choice. Use of a lateral external fixator was recently
      described as an optional procedure, but evidence is scarce. Methods We
      investigated the outcomes of upper limbs treated by either open reduction with
      internal fixation or closed reduction and external fixation. Results Twenty-one
      patients completed the long-term follow-up; 11 underwent open reduction, and 10
      underwent external fixation. Most patients in both groups reported excellent
      satisfaction. In both groups, the modified Disabilities of the Arm, Shoulder, and
      Hand score was extremely low and the average elbow range of motion was almost
      identical. Radiographic analysis consisting of Baumann's angle and the carrying
      angle revealed no statistical difference between the two groups. Discussion
      Optional treatment using a linear external fixator for complex nonreducible
      supracondylar humerus fractures yielded acceptable clinical and radiographic
      results, as with open reduction. Our sample size was small, but the promising
      results may assist in the implementation of an alternative surgical procedure,
      especially in more complicated cases involving flexion-type fractures or severe
      soft tissue damage and swelling.

PMID- 30198366
TI  - MicroRNA-145 attenuates IL-6-induced enhancements of sensitivity to UVB
      irradiation by suppressing MyD88 in HaCaT cells.
AB  - MicroRNAs (miRNAs/miRs) play vital roles in various immune diseases including
      systemic lupus erythematosus (SLE). The current study aimed to assess the role of
      miR-145 in interleukin-6 (IL-6)-treated HaCaT cells under ultraviolet B (UVB)
      irradiation and further explore the potential regulatory mechanism. HaCaT cells
      were pretreated with IL-6 and then exposed to UVB to assess the effect of IL-6 on
      sensitivity of HaCaT cells to UVB irradiation. The levels of miR-145 and MyD88
      were altered by transfection and the transfected efficiency was verified by
      quantitative reverse transcription polymerase chain reaction (qRT-PCR)/western
      blot analysis. Cell viability, percentage of apoptotic cells and expression
      levels of apoptosis-related factors were measured by trypan blue assay, flow
      cytometry assay, and western blot analysis, respectively. In addition, the levels
      of c-Jun N-terminal kinases (JNK) and nuclear factor-kappaB (NF-kappaB) signaling
      pathway-related factors were assessed by western blot analysis. IL-6 treatments
      significantly aggravated the reduction of cell viability and promotion of cell
      apoptosis caused by UVB irradiation in HaCaT cells. Interestingly, miR-145 level
      was augmented by UVB exposure and miR-145 mimic alleviated IL-6-induced increase
      of sensitivity to UVB irradiation in HaCaT cells, as dramatically increased cell
      viability and reduced cell apoptosis. Opposite effects were observed in miR-145
      inhibitor-transfected cells. Meanwhile, MyD88 was negatively regulated by miR-145
      and MyD88 mediated the regulatory effect of miR-145 on IL-6- and UVB-treated
      cells. In addition, miR-145 mimic inhibited the JNK and NF-kappaB pathways by
      down-regulating MyD88. In conclusion, the present study demonstrated that miR-145
      alleviated IL-6-induced increase of sensitivity to UVB irradiation by down
      regulating MyD88 in HaCaT cells.

PMID- 30198368
TI  - Risk Factors for Depression in Adolescents With ADHD: The Impact of Cognitive
      Biases and Stress.
AB  - OBJECTIVE: Youth diagnosed with ADHD are at heightened risk of depression.
      However, many do not develop depression. Individuals with specific cognitive
      biases are more likely to develop depression yet it remains untested whether
      these vulnerability-stress models apply to depression risk in youth with ADHD.
      METHOD: We examined whether interpretation and attention biases moderated the
      relation between stressful life events and depressive symptoms in a sample of
      adolescents ( Mage = 14.42) with ADHD ( n = 59) and without ADHD ( n = 36).
      RESULTS: Youth with ADHD experienced more stressful life events compared with
      those without ADHD. Interpretation biases moderated the association between
      stress and depressive symptoms in youth with and without ADHD. Attention biases
      moderated the association between stress and depressive symptoms in the non-ADHD
      youth only. CONCLUSION: These results enhance our understanding of vulnerability
      for depression in adolescence with ADHD and inform targeted prevention and
      treatment models during this critical developmental juncture.

PMID- 30198369
TI  - A practical self-made device in parathyroid autotransplantation for patients with
      secondary hyperparathyroidism.
AB  - Objective Secondary hyperparathyroidism (sHPT) is one of the most serious
      complications in patients on long-term hemodialysis. These patients may suffer
      from metabolic bone diseases, severe atherosclerosis, and undesirable
      cardiovascular events. Endoscopic parathyroidectomy with autotransplantation is a
      treatment option for those who do not respond to clinical management. This study
      aimed to investigate practical use of a self-made device in parathyroid
      autotransplantation for patients with sHPT, and to compare this device with
      ordinary surgical scissors. Methods A total of 15 patients with sHPT were treated
      with endoscopic parathyroidectomy and autotransplantation. Pieces of parathyroid
      tissue were squeezed in our self-made device and injected into the
      brachioradialis muscle. Sixteen patients with sHPT who were treated with
      traditional parathyroid transplantation served as controls. Serum levels of
      parathyroid hormone, alkaline phosphatase, calcium, phosphorus and intact
      parathyroid hormone were measured before and after surgery. Results Preoperative
      symptoms were alleviated, and serum parathyroid hormone and alkaline phosphatase
      levels, hyperphosphatemia, and hypercalcemia were improved or normalized in all
      of the patients in both groups. Pathological examinations showed that parathyroid
      cells remained active. Conclusion Application of our squeezing device is an
      economic, effective, and safe method in endoscopic parathyroidectomy and
      autotransplantation for patients with sHPT.

PMID- 30198371
TI  - Oral Health Status of Male Swedish Citizens at Admission to Prison.
AB  - The aim of the study was to describe oral health status as well as risk factors
      related to the oral health in a prison inmate population at admission. A sample
      of 186 men admitted to one of Sweden's prisons were examined and interviewed to
      collect information. The results indicate a high prevalence of untreated oral
      disease and oral health risk factors in the sample. Seventy-one percent of the
      study population indicated drug abuse. Only 4.9% were assessed with completely
      healthy periodontal tissues, and 66% showed at least one tooth with untreated
      caries. According to the current regulations on dental care for inmates, only 11%
      of the study population was entitled to basic dental treatment (except
      emergency).

PMID- 30198372
TI  - Achieving veracity: A study of the development and use of an information system
      for data analysis in preventive healthcare.
AB  - Within healthcare, information systems are increasingly developed to enable
      automatic analysis of the large amounts of data that are accumulated. A
      prerequisite for the practical use of such data analysis is the veracity of the
      output, that is, that the analysis is clinically valid. Whereas most research
      focuses on the technical configuration and clinical precision of data analysis
      systems, the purpose of this article is to investigate how veracity is achieved
      in practice. Based on a study of a project in Denmark aimed at developing an
      algorithm for stratification of citizens in preventive healthcare, this article
      confirms that achieving veracity requires close attention to the clinical
      validity of the algorithm. It also concludes, however, that the veracity in
      practice hinges critically on the citizens' ability to report high-quality data
      and the ability of the health professionals to interpret the outcome in the
      context of existing care practices.

PMID- 30198374
TI  - Interhemispheric communication and the preference for attitude consistent
      information.
AB  - The current study investigated the role of interhemispheric communication in
      selective exposure to information. Participants (N = 241) reported their attitude
      and attitude strength toward a controversial social topic, engaged in a selective
      exposure task, and completed the Poffenberger paradigm. As expected, participants
      demonstrated a moderate (d = 0.50) preference for attitude consistent information
      on the selective exposure task and attitude strength was a significant predictor
      of participants' information search tendencies. Furthermore, faster right-to-left
      interhemispheric transfer was also significantly associated with an increased
      preference for attitude consistent information. These findings highlight the
      potential role of the right hemispheric processes in the detection of cognitive
      inconsistency and in the implementation of dissonance reduction strategies.

PMID- 30198373
TI  - The macroenviromental control of cancer metabolism by p62.
AB  - Metabolic reprogramming is a hallmark of cancer, but most studies focus on the
      molecular alterations in cancer cells and much less is known on the role of
      cancer metabolism, from a holistic perspective, for tumor initiation and
      progression. Increasing epidemiological evidence highlights the tremendous impact
      that cancer progression has on the host metabolism, especially in cachexia.
      However, how this benefits the tumor still is not completely understood. Here we
      review current studies on fatty acid oxidation in tumor cells as a potential
      therapeutic target in cancer, and how the redistribution of lipids from fat
      reservoirs to the cancer cell in the micro- and macro-environment impacts
      tumorigenesis by helping the tumor fulfill its energetic demands at the expense
      of fat. In this context, we also discuss the critical role of the signaling
      adaptor p62/Sequestosome 1(SQSTM1) in adipocytes in mediating tumor-induced fat
      reprograming and the feedback of adipose tissue on tumor aggressiveness via
      osteopontin and its potential implications in obesity-promoted cancer and fat
      cachexia. Collectively these studies highlight the importance of the symbiotic
      collaboration between adipose tissue and tumor to modulate the cancer metabolic
      fitness.

PMID- 30198375
TI  - Implementation and Evaluation of a Physical Activity and Dietary Program in
      Federal Incarcerated Females.
AB  - The purpose of this 3-month quasi-experimental pilot study was to examine the
      effect of a physical activity and dietary education program on body mass index
      (BMI) and resilience. Participants were given data-storing pedometers to record
      their physical activity, attended classes on healthy eating, and used portion
      control tools from http://ChooseMyPlate.gov . MyPlate usage and commissary
      purchases were collected weekly. BMI and resilience scores were measured at
      baseline, 6 weeks, and 12 weeks. Twenty-nine female prisoners completed the
      study. There was a statistically significant reduction in BMI after 12 weeks
      (chi2 = 7.56, p = .023) and resilience levels increased but did not reach
      statistical significance (chi2 = 1.66, p = .437). A physical activity and dietary
      intervention delivered by a correctional health nurse practitioner was an
      efficacious approach to reducing BMI and improving resilience among female
      prisoners.

PMID- 30198377
TI  - The Perceptions of Sexual Assault Prevention According to Military Spouses.
AB  - Military spouses are at an increased vulnerability with regard to the potential
      of being sexually victimized. They are twice as likely as their civilian
      counterparts to experience sexual victimization. Despite the increased
      probability of sexual assault, not all military spouses perceive sexual assault
      and its prevention through the same lens. Recognizing that reality is subjective,
      the theoretical framework for this study was a constructivist paradigm. A
      qualitative case study was executed for the purpose of querying the perceptions
      of military spouses as it relates to sexual assault, its prevalence, and its
      prevention. The study employed the use of a web-based questionnaire consisting of
      11 open-ended questions that included two scenario-based questions designed to
      explore perceptions of sexual assault, the need for a military spouse prevention
      program, and the catalyst for bystander intervention. Questionnaire results from
      29 anonymous military wives whose husbands were affiliated with four out of the
      five branches of service were analyzed to gauge their perceptions specific to
      sexual assault and its prevention. The analysis of their responses resulted in
      the emergence of five themes related to sexual assault prevention that include
      the notion that military spouses view themselves as a vulnerable population for
      sexual victimization and its prevalence although little discussion is given to
      the topic. Results also indicated that a military spouse-targeted sexual assault
      prevention program is needed to familiarize military spouses with definitions of
      sexual assault and consent, reporting options, and victims' rights. The study
      also found that the majority of military spouses are not familiar with the
      resources and services available to victims of sexual assault. The overarching
      implication is that a prevention program for military spouses is needed to
      familiarize them with reporting options and services as well as mitigate
      occurrences of sexual assault through training and education.

PMID- 30198376
TI  - P53 enhances apoptosis induced by doxorubicin only under conditions of severe DNA
      damage.
AB  - We previously demonstrated that Bim is the main BH3-only protein replacing
      Bak/Bax from Bcl-xl to activate apoptosis in a p53-independent manner in response
      to doxorubicin in prostate cancer. However, the comparison of doxorubicin
      treatment between LNCaP cells carrying p53-wild type and PC3 cells carrying p53
      null suggested that p53 might be essential for maximizing apoptosis. Inhibition
      of ATM did not affect doxorubicin-induced apoptosis. Overexpression of p53 did
      not affect ABT-263-induced apoptosis and nevertheless, the combination of
      doxorubicin with ABT-263 induced higher apoptotic responses than did doxorubicin
      or ABT-263 alone. These results advocated that doxorubicin-induced DNA damage
      controls p53 function for intensifying apoptosis. Indeed, overexpression of p53
      only enhanced apoptosis under conditions of severe DNA damage induced by high
      concentrations of doxorubicin in LNCaP cells. Immunofluorescence staining showed
      vague gammaH2AX foci and enlarged nuclei in LNCaP cells in response to high
      concentrations of doxorubicin, en route to apoptosis. In addition, our results
      revealed that the apoptosis in response to DNA replication stress induced by CFS
      1686, a catalytic inhibitor of topoisomerase, is p53-independent. Interestingly,
      the combination of doxorubicin with CFS-1686 generated DNA damage and replication
      stress simultaneously, resulting in a synergistic apoptotic effect in prostate
      cancer cells. Thus, we concluded that p53 is a sensor for enhanced apoptosis in
      response to DNA damage stress, not DNA replication stress, at least in prostate
      cancer.

PMID- 30198380
TI  - Five weeks of immersive reminiscence therapy improves autobiographical memory in
      Alzheimer's disease.
AB  - We examined the effects of a new Immersive Reminiscence Therapy (IRT) programme
      on cognitive function, including autobiographical memory, in a sample Alzheimer's
      disease (AD) patients. A total of 43 AD patients with mild to moderate disease
      severity were randomly assigned to either an intervention group (n = 22, MMMSE =
      20.77), or a control group (n = 21, MMMSE = 19.24). The intervention group
      received one weekly group-based session of IRT for five weeks in an authentic
      1950s style museum environment, matching the time of the participants' youth. IRT
      included semi-structured conversations about the past. The control group received
      standard care. We assessed performance on cognitive function and autobiographical
      memory at baseline and post-intervention. Five weeks of IRT enhanced subsequent
      autobiographical memory performance, when participants were cued by concrete
      objects dated to their youth. Object-cued memories reported post intervention
      included a significantly higher degree of episodic details and higher word
      counts. The intervention showed no effect on the Autobiographical Memory
      Interview or word-cued recall. Global cognitive function and semantic
      autobiographical memory performance increased across time for both groups. Our
      findings demonstrate that immersion into a setting, rich on concrete cues dated
      to the participants' youth can improve autobiographical remembering.

PMID- 30198378
TI  - Regulation of Cenp-F localization to nuclear pores and kinetochores.
AB  - In metazoans, the assembly of kinetochores on centrometric chromatin and the
      dismantling of nuclear pore complexes are processes that have to be tightly
      coordinated to ensure the proper assembly of the mitotic spindle and a successful
      mitosis. It is therefore noteworthy that these two macromolecular assemblies
      share a subset of constituents. One of these multifaceted components is Cenp-F, a
      protein implicated in cancer and developmental pathologies. During the cell
      cycle, Cenp-F localizes in multiple cellular structures including the nuclear
      envelope in late G2/early prophase and kinetochores throughout mitosis. We
      recently characterized the molecular determinants of Cenp-F interaction with
      Nup133, a structural nuclear pore constituent. In parallel with two other
      independent studies, we further elucidated the mechanisms governing Cenp-F
      kinetochore recruitment that mainly relies on its interaction with Bub1, with
      redundant contribution of Cenp-E upon acute microtubule depolymerisation. Here we
      synthesize the current literature regarding the dual location of Cenp-F at
      nuclear pores and kinetochores and extend our discussion to the regulation of
      these NPC and kinetochore localizations by mitotic kinase and spindle
      microtubules.

PMID- 30198379
TI  - Proteolysis: a double-edged sword for the development of amyloidoses.
AB  - The yeast Saccharomyces cerevisiae has proven to be a useful model system to
      investigate the mechanism of prion generation and inheritance, to which studies
      in Sup35 made a great contribution. Recent studies demonstrated that 'protein
      misfolding and aggregation' (i.e. amyloidogenesis) is a common principle
      underlying the pathogenesis of neurodegenerative diseases including prion,
      amyotrophic lateral sclerosis (ALS), Perkinson's (PD), Alzheimer's (AD) diseases
      and polyglutamine (polyQ) diseases such as spinocerebellar ataxia (SCA) and
      Hantington's disease (HD). By these findings, the yeast has again been drawing
      increased attention as a useful system for studying neurodegenerative
      proteinopathies. So far, it has been reported that proteolytic cleavage of
      causative amyloidogenic proteins might affect the pathogenesis of the respective
      neurodegenerative diseases. Although those reports provide a clear
      phenomenological description, in the majority of cases, it has remained elusive
      if proteolysis is directly involved in the pathogenesis of the diseases.
      Recently, we have demonstrated in yeast that proteolysis suppresses prion
      generation. The yeast-based strategy might make a breakthrough to the unsolved
      issues.

PMID- 30198383
TI  - Repetitive Peripheral Sensory Stimulation and Upper Limb Performance in Stroke: A
      Systematic Review and Meta-analysis.
AB  - BACKGROUND: Enhancement of sensory input in the form of repetitive peripheral
      sensory stimulation (RPSS) can enhance excitability of the motor cortex and upper
      limb performance. OBJECTIVE: To perform a systematic review and meta-analysis of
      effects of RPSS compared with control stimulation on improvement of motor
      outcomes in the upper limb of subjects with stroke. METHODS: We searched studies
      published between 1948 and December 2017 and selected 5 studies that provided
      individual data and applied a specific paradigm of stimulation (trains of 1-ms
      pulses at 10 Hz, delivered at 1 Hz). Continuous data were analyzed with means and
      standard deviations of differences in performance before and after active or
      control interventions. Adverse events were also assessed. RESULTS: There was a
      statistically significant beneficial effect of RPSS on motor performance
      (standard mean difference between active and control RPSS, 0.67; 95% CI, 0.09
      1.24; I2 = 65%). Only 1 study included subjects in the subacute phase after
      stroke. Subgroup analysis of studies that only included subjects in the chronic
      phase showed a significant effect (1.04; 95% CI, 0.66-1.42) with no
      heterogeneity. Significant results were obtained for outcomes of body structure
      and function as well as for outcomes of activity limitation according to the
      International Classification of Function, Disability and Health, when only
      studies that included subjects in the chronic phase were analyzed. No serious
      adverse events were reported. CONCLUSIONS: RPSS is a safe intervention with
      potential to become an adjuvant tool for upper extremity paresis rehabilitation
      in subjects with stroke in the chronic phase.

PMID- 30198384
TI  - Relating Anticipatory Postural Adjustments to Step Outcomes During Loss of
      Balance in People With Parkinson's Disease.
AB  - BACKGROUND: Effective protective steps are critical for fall prevention, and
      anticipatory postural adjustments (APAs) after a perturbation but prior to
      protective steps affect step performance. Although APAs prior to protective steps
      are altered in people with Parkinson's disease (PD), whether these changes affect
      subsequent step performance is poorly understood. OBJECTIVE: Characterize the
      relationship between mediolateral APA size and protective step outcomes in
      response to anteroposterior balance perturbations in people with PD. METHODS:
      Twenty-eight individuals with PD completed 25 forward and 25 backward protective
      steps in response to support surface translations. Multilevel linear models
      related mediolateral APA size to protective step outcomes. RESULTS: During
      forward protective stepping, larger mediolateral APAs were associated with
      delayed ( P < .001) and larger ( P = .004) steps. Larger APAs were also
      associated with smaller mediolateral ( P < .001) but larger anterior-posterior
      center of mass movement at foot off ( P < .001). During backward stepping, larger
      APAs were associated with later steps ( P < .001) and smaller anterior-posterior
      margin of stability at first foot contact ( P < .001). During backward stepping,
      larger APAs were also associated with worse clinical (ie, UPDRS [Unified
      Parkinson's Disease Rating Scale]; P = .005) and balance (ie, MiniBEST [Mini
      Balance Evaluation Systems Test]; P = .021) outcomes. CONCLUSIONS: During forward
      protective stepping, larger APAs were associated with larger and later steps,
      suggesting APA size may have mixed effects on the subsequent step. During
      backward stepping, larger APAs were associated with worse stepping outcomes (ie,
      later steps, smaller anterior-posterior margin of stability, worse clinical
      outcomes). Interventions aimed at improving APAs in PD should monitor spatial and
      temporal protective step outcomes to ensure treatment does not negatively affect
      protective steps, particularly for forward stepping.

PMID- 30198382
TI  - Activation of the P2X7 receptor in midbrain periaqueductal gray participates in
      the analgesic effect of tramadol in bone cancer pain rats.
AB  - Background Cancer pain is a well-known serious complication in metastatic or
      terminal cancer patients. Current pain management remains unsatisfactory. The
      activation of spinal and supraspinal P2X7 receptors plays a crucial role in the
      induction and maintenance mechanisms of various kinds of acute or chronic pain.
      The midbrain periaqueductal gray is a vital supraspinal site of the endogenous
      descending pain-modulating system. Tramadol is a synthetic, centrally acting
      analgesic agent that exhibits considerable efficacy in clinically relieving pain.
      The purpose of this study was to determine whether the activation of P2X7
      receptor in the ventrolateral region of the periaqueductal gray (vlPAG)
      participates in the analgesic mechanisms of tramadol on bone cancer pain in rats.
      The bone cancer pain rat model was established by intratibial cell inoculation of
      SHZ-88 mammary gland carcinoma cells. The analgesic effects of different doses of
      tramadol (10, 20, and 40 mg/kg) were assessed by measuring the mechanical
      withdrawal threshold and thermal withdrawal latency values in rats by using an
      electronic von Frey anesthesiometer and radiant heat stimulation, respectively.
      Alterations in the number of P2X7 receptor-positive cells and P2X7 protein levels
      in vlPAG were separately detected by using immunohistochemistry and Western blot
      assay. The effect of intra-vlPAG injection of A-740003 (100 nmol), a selective
      competitive P2X7 receptor antagonist, on the analgesic effect of tramadol was
      also observed. Results The expression of P2X7 receptor in the vlPAG on bone
      cancer pain rats was mildly elevated, and the tramadol (10, 20, and 40 mg/kg)
      dose dependently relieved pain-related behaviors in bone cancer pain rats and
      further upregulated the expression of P2X7 receptor in the vlPAG. The intra-vlPAG
      injection of A-740003 pretreatment partly but significantly antagonized the
      analgesic effect of tramadol on bone cancer pain rats. Conclusions The injection
      of tramadol can dose dependently elicit analgesic effect on bone cancer pain rats
      by promoting the expression of the P2X7 receptor in vlPAG.

PMID- 30198386
TI  - A mitochondrial long noncoding RNA in atlantic cod harbors complex heteroplasmic
      tandem repeat motifs.
AB  - A heteroplasmic tandem repeat (HTR) array occupies 100 to 300 bp of the
      mitochondrial DNA control region in the Atlantic cod, and recently we noted that
      the repeat appeared integrated in a polyadenylated mitochondrial long noncoding
      RNA. Here we provide a more detailed analysis of the mitochondrial HTR in the
      mitochondrial genome of 134 Atlantic cod specimens. We report all specimens to
      harbor mitochondrial HTRs in the control region, and identified 26 distinct
      variants among the 402 repeat motifs assessed. Whereas most specimens contained
      HTR profiles of 2-5 copies consisting of the same 40-bp motif, 22 specimens
      showed compound HTR arrays of at least two types of motifs present in the same
      mitochondrial DNA molecule. We found HTR profiles to be highly conserved between
      different tissue types of a single individual, and strictly maternally inherited
      in a mating experiment between parental Atlantic cod expressing different HTR
      profiles and array motifs. We conclude that mitochondrial heteroplasmy in the
      control region is very common in Atlantic cod, and results in length heterogenity
      of the long noncoding RNA lncCR-H.

PMID- 30198387
TI  - Biochemical characteristics of cellulose and a green alga degradation by
      Gilvimarinus japonicas 12-2T, and its application potential for seaweed
      saccharification.
AB  - Cellulose is one of the major constituents of seaweeds, but reports of mechanisms
      in microbial seaweed degradation in marine environment are limited, in contrast
      to the multitude of reports for lignocellulose degradation in terrestrial
      environment. We studied the biochemical characteristics for marine cellulolytic
      bacterium Gilvimarinus japonicas 12-2T in seaweed degradation. The bacterial
      strain was found to degrade green and red algae, but not brown algae. It was
      shown that the bacterial strain employs various polysaccharide hydrolases
      (endocellulase, agarase, carrageenanase, xylanase, and laminarinase) to degrade
      seaweed polysaccharides. Electrophoretic analysis and peptide sequencing showed
      that the major protein bands on the electrophoresis gel were homologous to known
      glucanases and glycoside hydrolases. A seaweed hydrolysate harvested from the
      bacterial culture was found useful as a substrate for yeasts to produce ethanol.
      These findings will provide insights into possible seaweed decomposition
      mechanisms of Gilvimarinus, and its biotechnological potential for ethanol
      production from inedible seaweeds.

PMID- 30198388
TI  - Optimized beagle model for maxillary sinus floor augmentation via a mini-lateral
      window with simultaneous implant placement.
AB  - OBJECTIVE: This study was performed to establish an optimized beagle model for
      maxillary sinus floor augmentation via a mini-lateral window with simultaneous
      implant placement. METHODS: Twelve beagles underwent maxillary sinus floor
      augmentation via a mini-lateral window with simultaneous implant placement
      through sites selected by analyzing preoperative cone beam computed tomography
      (CBCT) images. During the experiment, no maxillary teeth were extracted and the
      infraorbital nerve was not severed. The osteotomy was only 5 mm in diameter. The
      implant stability quotient was measured, and postoperative CBCT was used to
      detect the condition of the sinus membrane and bone augmentation. RESULTS: The
      site corresponding to the tip of the highest dental cusp of the maxillary fourth
      premolar was suitable for the procedure, and the implant site was on the palatal
      bone plate. All implants achieved good primary stability. Postoperative CBCT
      showed no sinus membrane perforation, and the implants penetrated into the sinus
      cavity surrounded by bone substitute. CONCLUSION: The herein-described optimized
      model with mini-lateral osteotomy and without extraction or severing of the
      infraorbital nerve was minimally invasive, retained more lateral bone of the
      sinus, and achieved good sinus floor-lifting results. This model is highly
      reproducible and merits wider application.

PMID- 30198385
TI  - CD4+ memory T cells infected with latent HIV-1 are susceptible to drugs targeting
      telomeres.
AB  - The population of HIV reservoir in infected person is very small, but extremely
      long-lived and is a major obstacle for an HIV cure. We previously showed that
      cells with established HIV latency have deficiencies in DNA damage response
      (DDR). Here, we investigated ability of HIV-1 to interfere with telomere
      maintenance, and the effects of targeting telomeres on latently infected cells.
      Our results show that telomeres are elongated in cultured primary memory CD4 + T
      cells (TCM) after HIV-1 infection and when virus latency is established.
      Similarly, much longer telomeres were found in several Jurkat-derived latently
      infected cell lines, indicating that virus stimulates telomere elongation.
      Exposing primary CD4+ TCM cells to BRACO19, an agent targeting telomeres,
      resulted in a higher rate of apoptosis for infected cultures at day 3 post
      infection, during HIV-1 latency and for PMA-stimulated cultures with low level of
      HIV-1 reactivation. Importantly, BRACO19 induced apoptosis in infected cells with
      potency similar to etoposide and camptothecin, whereas uninfected cells were less
      affected by BRACO19. We also determined that apoptosis induced by BRACO19 is not
      caused by telomeres shortening, but is related to formation of gamma-H2AX,
      implicating DNA damage or uncapping of telomeres, which triggers genome
      instability. In conclusion, our results indicate that HIV-1 stimulates telomere
      elongation during latency, suggesting that HIV reservoir has greater capacity for
      clonal expansion and extended lifespan. Higher rates of apoptosis in response to
      BRACO19 treatment suggest that HIV reservoirs are more susceptible to targeting
      telomere maintenance and to inhibitors targeting DDR, which is also involved in
      stabilizing telomeres.

PMID- 30198389
TI  - Treatment for spoken and written word retrieval in the semantic variant of
      primary progressive aphasia.
AB  - This study investigated whether a treatment programme for spoken word retrieval,
      supplemented with written naming, was beneficial for an individual with right
      hemisphere dominant semantic variant of PPA (svPPA). Assessment and treatment
      were delivered remotely through Skype. Treatment consisted of two phases of
      lexical retrieval therapy (Repetition and Reading in the Presence of a Picture:
      RRIPP), with and without written responses (Phases 1 and 2 respectively), and a
      third treatment phase based on the procedures of Conceptual Enrichment (COEN)
      therapy. The first two phases of treatment resulted in short-lasting improvements
      in spoken and written word retrieval, with greater improvement in Phase 2 when
      written production was also required. Both treatment phases resulted in gains
      only for treated items, but generalised to different depictions to those treated.
      However, Phase 2 also resulted in significant improvement of treated items on a
      comprehension task. COEN treatment did not result in significant gains in word
      retrieval or comprehension. This study reinforces the value of a simple lexical
      retrieval treatment delivered remotely. It adds to the current evidence that
      anomia in svPPA can be responsive to treatment, but also shows that challenges
      remain regarding maintenance effects and the generalisation of treatment effects
      to connected speech.

PMID- 30198390
TI  - The structure of viral cathepsin from Bombyx mori Nuclear Polyhedrosis Virus as a
      target against grasserie: Docking and molecular dynamics simulations.
AB  - The viral cathepsin from Bombyx mori Nucleopolyhedrosis virus (BmNPV-Cath) is a
      broad-spectrum protease that participates in the horizontal transmission of this
      virus in silkworm by facilitating solubilization of the integument of infected
      caterpillars. When a B. mori farm is attacked by Bombyx mori Nucleopolyhedrosis
      virus (BmNPV), there are significant sericultural losses because no drugs or
      therapies are available. In this work, the structure of viral cathepsin BmNPV
      Cath was used as a target for virtual screening simulations, aiming to identify
      potential molecules that could be used to treat the infection. Virtual screening
      of the Natural Products library from the Zinc Database selected four molecules.
      Theoretical calculations of DeltaGbinding by the molecular mechanics Poisson
      Boltzmann surface analysis (MM-PBSA) method indicated that the molecule
      Zinc12888007 (Bm5) would have high affinity for the enzyme. The in vivo infection
      models of B. mori caterpillars with BmNPV showed that treatment with a dose of
      100 MUg Bm5 dissolved in Pluronic-F127 0.02% was able to reduce the mortality of
      caterpillars in 22.6%, however, it did not impede the liquefaction of dead
      bodies. Our results suggest a role of BmNPV-Cath in generating a pool of amino
      acids necessary for viral replication and indicate a mechanism to be exploited in
      the search for treatments for grasserie disease of the silkworm.

PMID- 30198392
TI  - Enhanced recovery after surgery protocol for prostate cancer patients undergoing
      laparoscopic radical prostatectomy.
AB  - Objective To determine the value of an enhanced recovery after surgery (ERAS)
      protocol for prostate cancer patients undergoing laparoscopic radical
      prostatectomy (LRP). Methods We conducted a retrospective cohort study using
      clinical data for 288 patients who underwent LRP in our hospital from June 2010
      to December 2016. A total of 124 patients underwent ERAS (ERAS group) and the
      remaining 164 patients were allocated to the control group. ERAS comprised
      prehabilitation exercise, carbohydrate fluid loading, targeted intraoperative
      fluid resuscitation and keeping the body warm, avoiding drain use, early
      mobilization, and early postoperative drinking and eating. Results The times from
      LRP to first water intake, first ambulation, first anal exhaust, first
      defecation, pelvic drainage-tube removal, and length of hospital stay (LOS) were
      all significantly shorter, and hospitalization costs and the incidence of
      postoperative complications were significantly lower in the ERAS group compared
      with the control group. No deaths or reoperations occurred in either group, and
      there were no readmissions in the ERAS group, within 90 days after surgery.
      Conclusion ERAS protocols may effectively accelerate patient rehabilitation and
      reduce LOS and hospitalization costs in patients undergoing LRP.

PMID- 30198391
TI  - Temporomandibular joint disorder determined by Fonseca anamnestic index and
      associated factors in 18- to 27-year-old university students.
AB  - OBJECTIVE: The aim of this study was to investigate temporomandibular disorder
      (TMD) and associated risk factors. METHODS: This study was conducted using 212
      university students. Based on the Fonseca anamnestic index, the population was
      divided into two groups: those with TMD and those without TMD. The two groups
      were compared in terms of global body posture, craniohorizontal and
      craniovertebral angles, neck and temporomandibular joint range of motion, stress
      level, and sleep quality. RESULTS: Stress level, sleep quality, and left cervical
      rotation were found to have statistical differences between the groups (p = 0.00,
      0.00, and 0.046, respectively). Sleep quality and stress level were found to be
      important risk factors for the presence of TMD (p = 0.017 and 0.00,
      respectively). DISCUSSION: In the prevention and treatment of TMD, a holistic
      approach that evaluates mechanical factors and psychosocial factors should be
      adopted.

PMID- 30198393
TI  - Parity and neural responses to social and non-social stimuli in pregnancy.
AB  - Prior reproductive experience, or parity, may contribute to differential neural
      responses to infant stimuli during pregnancy. We examined the P300 elicited by
      viewing infant and adult faces, as well as houses, in women pregnant with their
      first child and compared their neural responses to women who had at least one
      child prior to their current pregnancy. We found the P300 amplitude was larger in
      women pregnant with their first child as compared to pregnant women who had
      previously had children. This larger P300 was observed in response to all visual
      stimuli and was not specific to infant faces. Taken together, these findings
      indicate increased sensitivity toward social and non-social stimuli in pregnancy
      and indicate the importance of measuring parity in social neuroscience studies of
      pregnancy and motherhood.

PMID- 30198394
TI  - Ophthalmic complications following ocular penetration during routine dentistry in
      13 cats.
AB  - CASE HISTORY Thirteen cats developed ophthalmic complications following dental
      procedures in Australia and New Zealand between December 2014 and February 2018.
      All cats had at least one maxillary tooth extracted and some received a transoral
      maxillary nerve block. CLINICAL FINDINGS Ocular signs were identified at a median
      of 1.5 (min 0, max 14) days following elective dental procedures and included
      fibrin in the anterior chamber, aqueous flare, vision loss and miosis. Response
      to medical management was poor overall, with 7/13 (54%) cats undergoing
      subsequent enucleation and one cat was subjected to euthanasia shortly after the
      dental procedure due to ocular disease. The remaining five cats were managed
      medically. Of these, four exhibited signs of persistent inflammation at the last
      ophthalmic assessment, and one was subsequently subjected to euthanasia due to
      reasons unrelated to ocular health. Active inflammation resolved in one cat,
      however the lesions caused by previous inflammation persisted. PATHOLOGICAL
      FINDINGS Assessment of six enucleated globes showed a variety of pathological
      changes, with marked fibrinous exudation and suppurative inflammation as
      predominant features. A scleral penetration site was identified in three globes.
      Four globes had lens capsule rupture and phacoclastic uveitis. DIAGNOSIS
      Endophthalmitis following iatrogenic globe penetration during routine dental
      procedures. CLINICAL RELEVANCE This case series demonstrates that globe
      penetration during dental procedures carries a poor prognosis for the eye.
      Clinicians should be aware of the risks of ocular trauma during dental procedures
      in cats and great care should be taken to avoid ocular penetration, particularly
      during tooth extractions. Transoral maxillary nerve blocks should be avoided or
      used with extreme caution in cats.

PMID- 30198396
TI  - Aprotinin interacts with substrate-binding site of human dipeptidyl peptidase
      III.
AB  - Human dipeptidyl peptidase III (hDPP III) is a zinc-exopeptidase of the family
      M49 involved in final steps of intracellular protein degradation and in
      cytoprotective pathway Keap1-Nrf2. Biochemical and structural properties of this
      enzyme have been extensively investigated, but the knowledge on its contacts with
      other proteins is scarce. Previously, polypeptide aprotinin was shown to be a
      competitive inhibitor of hDPP III hydrolytic activity. In the present study,
      aprotinin was first investigated as a potential substrate of hDPP III, but no
      degradation products were demonstrated by MALDI-TOF mass spectrometry.
      Subsequently, molecular details of the protein-protein interaction between
      aprotinin and hDPP III were studied by molecular modeling. Docking and long
      molecular dynamics (MD) simulations have shown that aprotinin interacts by its
      canonical binding epitope with the substrate binding cleft of hDPP III. Thereby,
      free N-terminus of aprotinin is distant from the active-site zinc. Enzyme
      inhibitor complex is stabilized by intermolecular hydrogen bonding network,
      electrostatic and hydrophobic interactions which mostly involve constituent amino
      acid residues of the hDPP III substrate binding subsites S1, S1', S2, S2' and
      S3'. This is the first study that gives insight into aprotinin binding to an
      metallopeptidase.

PMID- 30198395
TI  - Security and Radical Assessment in Open, Laparoscopic, Robotic Colorectal Cancer
      Surgery: A Comparative Study.
AB  - PURPOSE: This retrospective study was designed to assess the safety and
      effectiveness of open, laparoscopic, robotic colorectal cancer surgery. METHODS:
      Three hundred patients with colorectal cancer who underwent curative resection in
      the First Affiliated Hospital of Zhengzhou University between February 2014 and
      May 2016 were included. Patients were classified into open surgery group,
      laparoscopic surgery group, and robot-assisted group. RESULTS: The blood loss in
      laparoscopic surgery group was less than that in open surgery group, and the
      blood loss in robot-assisted group less was than the open surgery group. The
      number of lymph node dissection in robot-assisted group was significantly larger
      than that in the open group ( P < .05). The distance between the lower edge of
      the tumor group and the distal margin in robotic group was longer than that of
      the laparoscopic surgery group and the open group ( P < .05). Three (2.8%) cases
      of urinary retention occurred in the open surgery group, 4 (3.92%) cases in the
      laparoscopic surgery group, and 1 (1.1%) case in the robot-assisted group, while
      2 (1.87%) cases of sexual dysfunction occurred in the open surgery group, 2
      (1.96%) cases in the laparoscopic surgery group, and 1 (1.1%) case in the robot
      assisted group. The urinary retention and sexual dysfunction rate did not differ
      between the 3 groups ( P > .05), but the minimally invasive group showed a
      certain advantage over the open group. CONCLUSION: Compared to the traditional
      open surgery, minimally invasive surgery (especially in robot-assisted group) has
      advantages such as less intraoperative bleeding, rapid postoperative recovery,
      and radical cure; open group, laparoscopic surgery group, and robot-assisted
      group have a similar incidence of postoperative complications, but reduction in
      the incidence of anastomotic leakage and intestinal obstruction. Robot-assisted
      group has the potential advantage for pelvic autonomic nerve protection.

PMID- 30198397
TI  - Wildlife diseases in New Zealand: recent findings and future challenges.
AB  - Our knowledge of diseases in New Zealand wildlife has expanded rapidly in the
      last two decades. Much of this is due to a greater awareness of disease as a
      cause of mortality in some of our highly threatened species or as a limiting
      factor to the successful captive rearing of intensely managed species such as
      hihi (Notiomystis cincta), kiwi (Apteryx spp.) and kakapo (Strigops habroptilus).
      An important factor contributing to the increase of our knowledge has been the
      development of new diagnostic techniques in the fields of molecular biology and
      immunohistochemistry, particularly for the diagnosis and epidemiology of viral
      and protozoan diseases. Although New Zealand remains free of serious exotic
      viruses there has been much work on understanding the taxonomy and epidemiology
      of local strains of avipox virus and circoviruses. Bacterial diseases such as
      salmonellosis, erysipelas and tuberculosis have also been closely investigated in
      wildlife and opportunist mycotic infections such as aspergillosis remain a major
      problem in many species. Nutritional diseases such as hyperplastic goitre due to
      iodine deficiency and metabolic bone disease due to Ca:P imbalance have made
      significant impacts on some captive reared birds, while lead poisoning is a
      problem in some localities. The increasing use of wildlife translocations to
      avoid the extinction of threatened species has highlighted the need for improved
      methods to assess the disease risks inherent in these operations and other
      intensive conservation management strategies such as creching young animals. We
      have also become more aware of the likelihood of inbreeding suppression as
      populations of many species decrease or pass through a genetic bottleneck.
      Climate change and habitat loss, however, remain the greatest threats to
      biodiversity and wildlife health worldwide. Temperature changes will affect our
      wildlife habitats, alter the distribution of disease vectors and wildlife
      predators, or directly harm threatened species in vulnerable localities.

PMID- 30198398
TI  - Is PostureScreen(r) Mobile app an accurate tool for dentists to evaluate the
      correlation between malocclusion and posture?
AB  - OBJECTIVE: To determine whether PostureScreen(r) Mobile app is a useful, simple
      tool that is accessible for dentists to evaluate the correlation between
      malocclusion and posture. METHODS: Twenty-nine subjects underwent static and
      dynamic dental occlusion examinations and a postural exam with PostureScreen(r)
      Mobile app, a photographic method. The subjects were divided into groups
      depending on their static and dynamic occlusion features. The postural parameters
      were then compared between these groups. RESULTS: Statistically significant
      differences (p < 0.05) for some postural parameters were obtained for Angle Class
      1 vs. 2 and 3 and for the passive interference group and active premature
      contacts group during left lateral movement. There were no statistically
      significant differences regarding protrusion and right lateral movement.
      DISCUSSION: Dental occlusion anomalies and posture pathological modifications can
      be inter-related. PostureScreen(r) Mobile app might represent a useful tool in
      the early diagnosis of dental occlusion pathology.

PMID- 30198399
TI  - Waste reduction through Kaizen approach: A case study of a company in India.
AB  - The growth in manufacturing activities for economic development is putting a lot
      of pressure on the environment. One such impact is due to generation of waste
      from hazardous material. The best way for hazardous waste management is either
      elimination or substitution with non-hazardous material. The case study in the
      present paper is focused on the problem of hazardous waste reduction in absence
      of non-hazardous substitution. In absence of any non-hazardous substitute of
      hazardous material, waste generation can be reduced using improvement techniques
      such as Kaizen to improve the manufacturing process. An Indian company improved
      the manufacturing procedure with very low cost to reduce waste generation of
      hazardous material. The outcome of this Kaizen project is the reduction of waste
      by 13.8% at very low cost. Along with waste reduction, cost saving, and other
      resource savings are another benefits. This case study provides insight about the
      use of Kaizen for environmentally sustainable manufacturing.

PMID- 30198400
TI  - Bioelectricity production from fermentable household waste in a dual-chamber
      microbial fuel cell.
AB  - In this study, the use of a dual-chamber microbial fuel cell for the production
      of bioelectricity from a food residue biomass (FORBI) product was investigated.
      Food residue biomass was produced by drying and shredding the pre-sorted
      fermentable fraction of household food waste collected door-to-door in the
      Municipality of Halandri, Athens, Greece. Different organic loads of food residue
      biomass expressed as chemical oxygen demand (COD) were examined (0.7, 0.9, 1.4,
      2.8, 6 and 14 g COD L-1, respectively). It was observed that an increase of the
      initial concentration of the final extract resulted in a corresponding increase
      in the operating time. The microbial fuel cell potential increased from 33.3 mV
      to 46 mV as the concentration was increased from 0.7 to 14 g COD L-1. The best
      performance in terms of maximum power density (29.6 mW m-2) corresponding to a
      current density of 88 mA m-2 was observed for 6 g COD L-1. Setting the external
      resistance at its optimal value (Rext = 2 kOmega) as determined by polarisation
      experiments, Pyield drastically increased to 13.7 and 17.3 Joule (g FORBI)-1 in
      two consecutive cycles. The results demonstrate that readily biodegradable
      substrates, such as food residue biomass, can be effectively used for enhanced
      bioelectricity harvesting in a microbial fuel cell.

PMID- 30198401
TI  - Decreased Expression of ZWINT is Associated With Poor Prognosis in Patients With
      HCC After Surgery.
AB  - BACKGROUND: ZW10 interactor was recently reported to correlate with human
      cancers. However, the prognostic value of ZW10 interactor in hepatocellular
      carcinoma was not reported. METHODS: The expression level of ZW10 interactor was
      evaluated by Western blot and immunohistochemistry using tissue microarray. In
      the present study, we used 5 pairs of hepatocellular carcinoma and peritumoral
      frozen tissues for Western blot, and 70 paired paraffin-embedded hepatocellular
      carcinoma and peritumoral tissues as expression pattern cohort (cohort 1), and
      280 paraffin-embedded hepatocellular carcinoma tissues were used as prognostic
      cohort (cohort 2). The integral optic density representing the expression level
      of ZW10 interactor in each tissue sample, was calculated using Image-Pro Plus.
      The integral optic density was added to the X-tile software for calculating the
      outcome-based cut point. Kaplan-Meier and Cox regression were used to evaluate
      the prognostic values. RESULTS: The expression level ZW10 interactor was
      decreased in hepatocellular carcinoma tissues in 85.7% (60/70) of the cases
      compared to the corresponding peritumoral tissues evaluated by
      immunohistochemistry. Similar result was obtained by Western blot analysis using
      frozen tissue. Expression of ZW10 interactor was closely correlated with age ( P
      = .0001) and liver cirrhosis in cohort 1 and tumor node metastasis ( P = .018),
      tumor size ( P = .005), and vascular invasion ( P = .022) in cohort 2 based on
      chi2 analyses. Survival analyses indicated that patients with hepatocellular
      carcinoma having low ZW10 interactor expression had a shorter overall survival
      time and time to recurrence compared to cases with high ZW10 interactor
      expression in the prognostic cohort ( P < .0001 for both overall survival and
      time to recurrence ). Univariate and multivariate Cox analyses indicated that
      ZW10 interactor was an independent prognostic factor for overall survival ( P =
      .033). CONCLUSIONS: The present study clearly showed that ZW10 interactor was
      frequently decreased in hepatocellular carcinoma compared to nontumoral liver
      tissues, and ZW10 interactor could serve as a potential prognostic marker in
      patients with hepatocellular carcinoma after surgery.

PMID- 30198402
TI  - Mapping mammalian replication domains using the ion torrent semiconductor
      sequencing platform.
AB  - Here, we show that semiconductor-based sequencing technology can be used to map
      mammalian replication domains, chromosomal units with similar DNA replication
      timing. Replicating DNA purified from mammalian cells was successfully sequenced
      by the Ion Torrent platform. The resultant replication domain map of mouse
      embryonic stem cells is comparable to those obtained by the conventional
      microarray-based method.

PMID- 30198404
TI  - Bioconversion of Scotch broom into a high-quality organic fertiliser:
      Vermicomposting as a sustainable option.
AB  - Wild Scotch broom ( Cytisus scoparius (L.) Link) shrubs are widely distributed
      throughout the world and, in some countries, are considered to be a threat to
      other plant species. The use of plant biomass from Scotch broom as a fertiliser
      seems to be the optimum solution for its disposal because it contains
      considerable amounts of macronutrients. However, its direct application to soils
      may cause phytotoxicity due to the release of polyphenols, which could negatively
      affect crop growth. This study evaluated the efficiency of vermicomposting in
      processing this leguminous plant on an industrial scale. Vermicomposting
      substantially reduced the biomass of Scotch broom (by 84%), mainly as a result of
      the loss of volatile solids. Simultaneously, the initial population of earthworms
      ( Eisenia andrei) increased remarkably throughout the process, offering the
      possibility of obtaining earthworm protein for animal feed. A nutrient-rich and
      stabilised peat-like material without polyphenol-associated phytotoxicity was
      obtained after 42 days of vermicomposting. Lower values of microbial biomass and
      activity, indicative of stabilised materials, were recorded at the end of the
      trial. These findings suggest that vermicomposting is an environmentally sound
      management system for Scotch broom and could easily be scaled up for industrial
      application.

PMID- 30198403
TI  - Study on Attenuating Angiogenesis and Epithelial-Mesenchymal Transition (EMT) of
      Non-Small Cell Lung Carcinoma (NSCLC) by Regulating MAGEC2.
AB  - OBJECTIVE: To investigate the role of MAGE family member C2 in angiogenesis and
      epithelial-mesenchymal transition of non-small cell lung carcinoma. METHODS: The
      Cancer Genome Atlas data set was analyzed to filter the highly expressed gene
      melanoma antigen family C2 in non-small cell lung carcinoma. Quantitative reverse
      transcription-polymerase chain reaction was performed to verify the
      overexpression of melanoma antigen family C2 in non-small cell lung carcinoma
      cell lines. Melanoma antigen family C2 complementary DNA and short hairpin RNA
      (shRNA) were transfected into SK-MES-1 cells to regulate melanoma antigen family
      C2 expression. Cell Counting Kit-8 assay, flow cytometry, wound healing assay,
      and Transwell assay were performed to investigate the effect of melanoma antigen
      family C2 on proliferation, apoptosis, migration, and invasion of SK-MES-1 cell
      line. Western blot was used to detect the expression of epithelial-mesenchymal
      transition markers. Enzyme-linked immunosorbent assay was performed to
      investigate the secretion of vascular endothelial growth factor, and tube
      formation assay was conducted to explore the effect of melanoma antigen family C2
      on angiogenesis ability of the tumor. Tumor xenograft on nude mice and
      immunohistochemical/hematoxylin and eosin staining were also performed to detect
      the influence of melanoma antigen family C2 on growth and metastasis of non-small
      cell lung carcinoma cells. RESULTS: Melanoma antigen family C2 was highly
      expressed in non-small cell lung carcinoma cells; melanoma antigen family C2
      promoted the expression of epithelial-mesenchymal transition-related proteins as
      well as enhance the secretion of vascular endothelial growth factor and promote
      angiogenesis; melanoma antigen family C2 promoted proliferation, migration, and
      invasion and suppressed apoptosis of non-small cell lung carcinoma cells. It
      could also facilitate growth and metastasis of non-small cell lung carcinoma in
      vivo. CONCLUSION: Melanoma antigen family C2 was a critical factor of
      angiogenesis and epithelial-mesenchymal transition in non-small cell lung
      carcinoma.

PMID- 30198405
TI  - Usefulness of surgical pleth index-guided analgesia during general anesthesia: a
      systematic review and meta-analysis of randomized controlled trials.
AB  - OBJECTIVE: Previous studies comparing surgical pleth index (SPI)-guided and
      conventional analgesia have shown differing results. Therefore, we compared the
      intraoperative opioid requirement, extubation time, postoperative pain scores,
      and perioperative adverse events between these two modalities. METHODS: A
      comprehensive literature search was conducted to identify randomized controlled
      trials comparing the intraoperative opioid requirement and other outcomes between
      the two modalities. The mean difference (MD) or the pooled risk ratio and
      corresponding 95% confidence interval (CI) were used for analysis. A
      heterogeneity (I2) assessment was performed. RESULTS: Six randomized controlled
      trials comparing 463 patients were included. Intraoperative opioid consumption
      was significantly lower in the SPI-guided than conventional analgesia group
      (standardized MD, -0.41; 95% CI, -0.70 to -0.11; I2 = 53%). No significant
      intergroup difference was observed in the pain score on the first postoperative
      day or the incidence of perioperative adverse events. The extubation time was
      considerably shorter in the SPI-guided than conventional analgesia group (MD, 
      1.91; 95% CI, -3.33 to -0.49; I2 = 67%). CONCLUSIONS: Compared with conventional
      analgesia, SPI-guided analgesia can reduce intraoperative opioid consumption and
      facilitate extubation. Moreover, no intergroup difference was observed in the
      degree of postoperative pain or incidence of perioperative adverse events.

PMID- 30198408
TI  - In Memoriam: Arnold P. Gold (1926-2018).

PMID- 30198407
TI  - In Memoriam: Alan Aron, MD (October 15, 1933-December 26, 2017).

PMID- 30198409
TI  - In Memoriam: Paul Richard Dyken, MD (1934-2017).

PMID- 30198411
TI  - Fine particulate matter (PM2.5), a risk factor of rat gestational diabetes with
      altered blood glucose and pancreatic GLUT2 expression.
AB  - Recent studies have shown an association between air pollution and diabetic risk.
      This study was to investigate the impact of fine particulate matter (PM2.5) on
      glucose consequences and pancreas glucose transporter 2 (GLUT2) expression and
      its related mechanisms in a gestational diabetes mellitus (GDM) rat model. GDM
      rats were exposed to a low PM2.5 dose while the controls received saline.
      Interleukin-6 (IL-6) and blood routine tests (BRT) were detected for analyzing
      coagulation and inflammation. Pancreas tissues underwent pathologic examination,
      the levels of homogenate glutathione peroxidase (GSH-Px), and methane
      dicarboxylic aldehyde (MDA) were detected for oxidative stress estimation, and
      the degree of GLUT2 expression of pancreas was analyzed. There were lower
      maternal body weight gain and fetal weight in the PM2.5 group. Exposure to PM2.5
      caused increased absorbed blastocyst number and postprandial blood glucose (PBG)
      blood mono-nuclear cells (PBMC), platelets, and IL-6 levels. The pancreas of
      PM2.5 exposed rats revealed inflammation under pathological examination. The
      pancreatic GSH-Px significantly reduced and MDA increased and GLUT2 protein
      expression decreased after exposure. Our study provides direct evidence that
      PM2.5 exposure can result in glycemic consequences in GDM rats. The oxidative
      response and inflammation are involved in PM2.5 increased risk of adverse
      maternal and fetal consequences.

PMID- 30198412
TI  - Discrepancy between Health Care Rationing at the Bedside and Policy Level.
AB  - BACKGROUND: Whether doctors at the bedside level should be engaged in health care
      rationing is a controversial topic that has spurred much debate. From an
      empirical point of view, a key issue is whether there exists a behavioral
      difference between rationing at the bedside and policy level. Psychological
      theory suggests that we should indeed expect such a difference, but existing
      empirical evidence is inconclusive. OBJECTIVE: To explore whether rationing
      decisions taken at the bedside level are different from rationing decisions taken
      at the policy level. METHOD: Behavioral experiment where participants ( n = 573)
      made rationing decisions in hypothetical scenarios. Participants (medical and
      nonmedical students) were randomly assigned to either a bedside or a policy
      condition. Each scenario involved 1 decision, concerning either a life-saving
      medical treatment or a quality-of-life improving treatment. All scenarios were
      identical across the bedside and policy condition except for the level of
      decision making. RESULTS: We found a discrepancy between health care rationing at
      policy and bedside level for scenarios involving life-saving decisions, where
      subjects rationed treatments to a greater extent at the policy level compared to
      bedside level (35.6% v. 29.3%, P = 0.001). Medical students were more likely to
      ration care compared to nonmedical students. Follow-up questions showed that
      bedside rationing was more emotionally burdensome than rationing at the policy
      level, indicating that psychological factors likely play a key role in explaining
      the observed behavioral differences. We found no difference in rationing between
      bedside and policy level for quality-of-life improving treatments (54.6% v.
      55.7%, P = 0.507). CONCLUSIONS: Our results indicate a robust "bedside effect" in
      the life-saving domain of health care rationing decisions, thereby adding new
      insights to the understanding of the malleability of preferences related to
      resource allocation.

PMID- 30198414
TI  - Assessment of Serratia sp. isolated from iron ore mine in hexavalent chromium
      reduction: kinetics, fate and variation in cellular morphology.
AB  - Serratia sp. strain SU.ISM.1 was isolated from Noamundi iron ore mines for the
      first time and was observed for hexavalent chromium reduction, and growth
      kinetics modelling was applied for bacterial chromium reduction. For 4-8 ppm of
      hexavalent chromium concentration, complete reduction was observed within 36 h
      when the selected isolate was applied, and for 12-20 ppm chromium concentration,
      complete reduction was achieved within 48 h. The viable biomass concentration
      increased up to 36 h of treatment time, after which the biomass concentration
      gradually declined. The Aiba model of product inhibition growth kinetics best
      described the growth of biomass in the presence of hexavalent chromium. The total
      mass conversion of Cr(VI) to Cr(III) for 4, 8, 12, 16 and 20 ppm was found to be
      94.9%, 88.5%, 74.66%, 70.75% and 78.8%, respectively. The AFM and FESEM studies
      showed that the roughness of the cell surface increased with increasing
      concentration of hexavalent chromium, probably due to adsorption of chromium.

PMID- 30198413
TI  - A Systematic Literature Review on Salvage Radiotherapy for Local or Regional
      Recurrence After Previous Stereotactic Body Radiotherapy for Lung Cancer.
AB  - PURPOSE: The purpose of this review article was to summarize available data on
      the efficacy and safety of salvage radiotherapy for isolated local or regional
      recurrence after prior stereotactic body radiotherapy for lung cancer. METHODS:
      Studies were systematically searched on PubMed, following which suitable papers
      were selected. Reported outcomes and toxicities were qualitatively reviewed.
      RESULTS: Nineteen papers, which were retrospective studies based on single
      institution experiences, were selected. Sixteen papers were on salvage
      radiotherapy for local tumor recurrence, and the remaining 3 papers evaluated
      radiotherapy for regional failures after stereotactic body radiotherapy for lung
      cancer. Patient cohorts in the selected papers seemed very frail with 2-year
      survival of 30% to 40% after the salvage. Local control was reported to be
      approximately 60% to 70%, which is worse than that after primary stereotactic
      body radiotherapy. Reported rates of toxicity grade 3 or worse were considered
      acceptable. Larger target volume and central tumor localization were suggested as
      risk factors for severe toxicities. Dosimetric data on patients having toxicities
      were found to help with considering dose constraints for organs at risk.
      CONCLUSION: Based on data from a limited number of articles, salvage radiotherapy
      is a reasonable treatment option for select patients with local or regional tumor
      recurrence after prior stereotactic body radiotherapy for lung cancer. Optimal
      patient selection and dose prescription can be clarified with a larger study that
      include more data on experiences with salvage radiotherapy.

PMID- 30198415
TI  - Clarifying the Framework for 21st Century School Nursing PracticeTM in Research.

PMID- 30198416
TI  - School Nurses' Lifestyle Practices and Health Status: A Call to Action.

PMID- 30198417
TI  - Testing modified zeros for Poisson regression models.
AB  - Excessive zeros are common in practice and may cause overdispersion and
      invalidate inferences when fitting Poisson regression models. Zero-inflated
      Poisson regression models may be applied if there are inflated zeros; however, it
      is desirable to test if there are inflated zeros before such zero-inflated
      Poisson models are applied. Assuming a constant probability of being a structural
      zero in a zero-inflated Poisson regression model, the existence of the inflated
      zeros may be tested by testing whether the constant probability is zero. In such
      situations, the Wald, score, and likelihood ratio tests can be applied. Without
      specifying a zero-inflated Poisson model, He et al. recently developed a test by
      comparing the amount of observed zeros with that expected under the Poisson
      model. In this paper, we develop a closed form for the test and compare it with
      the Wald, score, and likelihood ratio tests through simulation studies. The
      simulation studies show that the test of He et al. is the best in controlling
      type I errors, while the score test generally has the least power among the
      tests. The tests are illustrated with two real data examples.

PMID- 30198418
TI  - Ubiquitin-Proteasome Axis, Especially Ubiquitin-Specific Protease-17 ( USP17)
      Gene Family, is a Potential Target for Epithelial-Mesenchymal Transition in High
      Grade Serous Ovarian Cancer.
AB  - OBJECTIVES: To investigate gene expression differences and related functions
      between primary tumor, malignant cells in ascites, and metastatic peritoneal
      implant in high-grade serous ovarian cancer. METHODS: Biopsies from primary
      tumor, peritoneal implant, and ascites were collected from 10 patients operated
      primarily for high-grade, advanced-staged serous ovarian cancer. Total RNA
      isolation was performed from collected tissue biopsy and fluid samples, and RNA
      expression profile was measured. Messenger RNA expression profiles of 3 different
      groups were compared. Functional analyses of candidate genes were carried out by
      gene ontology and pathway analysis. RESULTS: There were significant differences
      in the expression of 5 genes between primary tumor and peritoneal implant, 979
      genes between primary tumor and malignant cells in ascites, and 649 genes between
      peritoneal implant and malignant cells in ascites. Three commonly enriched gene
      ontology functions between "primary tumor and malignant cells in the ascites" and
      "peritoneal implant and malignant cells in the ascites" were protein
      deubiquitination, ubiquitin-dependent protein catabolism, and apoptotic
      processes. All genes related to these functions belonged to USP17 gene family.
      CONCLUSION: Gene expression difference between primary tumor and the peritoneal
      implant is not as much as the difference between primary tumor and free cells in
      the ascites. These results show that malignant cells in the ascites return into
      its genetic origin after they invade on the peritoneum. Significantly increased
      expression of DUB-enzyme genes, SNAR gene family, and ribosomal pathway genes in
      epithelial-mesenchymal transition suggests that this regulation is ubiquitin
      proteasome dependent. Especially, this is the first study that offers USP17 as a
      potential target for epithelial-mesenchymal transition.

PMID- 30198419
TI  - The Mindful Body: A Phenomenology of the Body With Multiple Sclerosis.
AB  - For people living with multiple sclerosis (MS), one's own body may no longer be
      taken for granted but may become instead an insistent presence. In this article,
      we describe how the body experience of people with MS can reflect an ongoing
      oscillation between four experiential dimensions: bodily uncertainty, having a
      precious body, being a different body, and the mindful body. People with MS can
      become engaged in a mode of permanent bodily alertness and may demonstrate
      adaptive responses to their ill body. In contrast to many studies on health and
      illness, our study shows that the presence of the body may not necessarily result
      in alienation or discomfort. By focusing the attention on the body, a sense of
      well-being can be cultivated and the negative effects of MS only temporarily
      dominate experience. Rather than aiming at bodily dis-appearance, health care
      professionals should therefore consider ways to support bodily eu-appearance.

PMID- 30198420
TI  - Transient-Evoked Otoacoustic Emissions Reflect Audiometric Patterns of Age
      Related Hearing Loss.
AB  - Distinct forms of age-related hearing loss are hypothesized based on evidence
      from animal models of aging, which are identifiable in human audiograms. The
      Sensory phenotype results from damage (e.g., excessive noise or ototoxic drugs)
      to outer hair cells and sometimes inner hair cells, producing large threshold
      increases predominately at high frequencies. The Metabolic phenotype results from
      a decline in endocochlear potential that can reduce outer hair cell motility
      throughout the cochlea, producing gradually sloping thresholds from lower to
      higher frequencies. Finally, the combined Metabolic + Sensory phenotype results
      in low-frequency losses similar to the Metabolic phenotype and high-frequency
      losses similar to the Sensory phenotype. Because outer hair cell function appears
      to be affected differently in each phenotype, this study used audiograms from 618
      adults aged 50 to 93 years ( n = 1,208 ears) to classify phenotypes and
      characterize differences in transient-evoked otoacoustic emission (TEOAE) data.
      Significant phenotype differences were observed in frequency-band TEOAEs and
      configuration (intercept and slope), including large and broadly distributed
      TEOAE reductions for Metabolic and Metabolic + Sensory ears and more focused high
      frequency TEOAE reductions for Sensory ears. These findings are consistent with
      metabolic declines that reduce cochlear amplification across a broad range of
      frequencies and more basally situated, high-frequency declines in sensory hearing
      loss. The results provide further validation for the classification of age
      related hearing loss phenotypes based on audiograms and show human TEOAE declines
      that are highly consistent with animal models.

PMID- 30198421
TI  - P4HA3 is Epigenetically Activated by Slug in Gastric Cancer and its Deregulation
      is Associated With Enhanced Metastasis and Poor Survival.
AB  - Prolyl 4-hydroxylase alpha subunit is the enzymic active site of prolyl 4
      hydroxylase, which is a critical enzyme to maintain the stability of newly
      synthesized collagens. The expression profile and functional role of P4HA3 in
      gastric cancer have not been explored. In the Cancer Genome Atlas-Stomach Cancer,
      P4HA3 RNA is significantly upregulated in gastric cancer than in normal stomach
      tissues. In the Human Protein Atlas, Prolyl 4-hydroxylase alpha subunit is not
      detectable by immunohistochemistry staining in normal stomach tissues, but it has
      weak staining in 7 of 12 gastric cancer tissues. Further study showed that SNAI2
      (encoding Slug) is highly coexpressed with P4HA3 (Pearson r = 0.70) in Cancer
      Genome Atlas-Stomach Cancer. In vitro cell assay showed that Slug could
      efficiently bind to the P4HA3 promoter and increase its transcription. P4HA3 exon
      array data in Cancer Genome Atlas-Stomach Cancer revealed that 2 exons are
      significantly upregulated in M1 (N = 27) cases than in M0 (N = 367) cases. In MKN
      45 and AGS cells, P4HA3 upregulation could enhance cell motility and
      invasiveness. In Cancer Genome Atlas-Stomach Cancer, high P4HA3 exon expression
      is associated with significantly worse 5-year and 10-year overall survival ( P =
      .007 and .009, respectively). Data mining in Kaplan-Meier plotter also showed
      that high P4HA3 expression is related to unfavorable overall survival (hazard
      ratio: 1.54, 95% confidence interval: 1.23-1.93, P < .001) and first progression
      free survival (hazard ratio: 1.64, 95% confidence interval: 1.29-2.1, P < .001).
      Based on findings above, we infer that P4HA3 is epigenetically activated by Slug,
      and its deregulation is associated with enhanced metastasis and poor survival of
      gastric cancer.

PMID- 30198422
TI  - Lymph node CXCL17 messenger RNA: A new prognostic biomarker for colon cancer.
AB  - Lymph node metastasis is the most important prognostic characteristic of
      colorectal cancer. Carcinoembryonic antigen messenger RNA was shown to detect
      tumor cells that have disseminated to lymph nodes of colorectal cancer patients
      and to be at least as good as the hematoxylin and eosin method to predict
      survival in colorectal cancer patients. CXCL17 was recently shown to be
      ectopically expressed in colon cancer tumors. Therefore, CXCL17 may serve as
      prognostic marker alone or in combination with carcinoembryonic antigen. CXCL17
      and carcinoembryonic antigen messenger RNA levels were determined using
      quantitative reverse transcription polymerase chain reaction with RNA copy
      standard in 389 lymph nodes of 120 colon cancer patients (stages I-IV) and 67
      lymph nodes of 12 control patients with inflammatory bowel disease as well as in
      68 primary tumors and 30 normal colon tissue samples. Lymph nodes of colon cancer
      patients were analyzed for CXCL17 and carcinoembryonic antigen protein expression
      by immunohistochemistry. CXCL17 messenger RNA was expressed in primary tumors at
      high levels, while it was barely detected in normal colon tissue ( p < 0.0001).
      Similarly, CXCL17 messenger RNA levels were significantly higher in hematoxylin-
      and eosin-positive (hematoxylin and eosin (+)) lymph nodes compared to
      hematoxylin- and eosin-negative nodes ( p < 0.0001). CXCL17 messenger RNA levels
      were investigated in lymph nodes grouped according to carcinoembryonic antigen
      messenger RNA levels: low (-), intermediate (int), and high (+). CXCL17 messenger
      RNA levels were higher in the carcinoembryonic antigen (int) and carcinoembryonic
      antigen (+) groups compared to the carcinoembryonic antigen (-) group ( p = 0.03
      and p < 0.0001, respectively). In lymph nodes of stage III and IV patients,
      CXCL17 messenger RNA levels correlated with carcinoembryonic antigen messenger
      RNA levels ( p < 0.0001, r = 0.56 and p = 0.0002, r = 0.66, respectively).
      Staining of consecutive lymph node sections for CXCL17 and carcinoembryonic
      antigen demonstrated that the same cells expressed both proteins. Altogether,
      these results indicate that CXCL17 in lymph nodes is expressed by tumor cells.
      Patients were grouped according to the CXCL17 messenger RNA levels in the highest
      lymph node with low levels (-) and high levels (+). CXCL17(+) colon cancer
      patients showed 2.8-3.6 fold increased risk for recurrence ( p = 0.03) and
      decreased mean disease-free survival time of 8 months compared to CXCL17(-) colon
      cancer patients ( p = 0.03). CXCL17(+) carcinoembryonic antigen (int) colon
      cancer patients showed increased risk for recurrence by 8.3 fold ( p = 0.04) and
      decreased mean disease-free survival time of 46 months compared to CXCL17(-)
      carcinoembryonic antigen (int) colon cancer patient at follow-up after 12 years (
      p = 0.02). The presence of tumor cells expressing CXCL17 in regional lymph nodes
      is a sign of poor prognosis. Analysis of CXCL17 messenger RNA is particularly
      useful to detect less differentiated colon cancer tumors expressing relatively
      low carcinoembryonic antigen messenger RNA levels. Thus, CXCL17 messenger RNA in
      combination with carcinoembryonic antigen messenger RNA may be used as a
      complementary tool to the hematoxylin and eosin method for detection of poorly
      differentiated, aggressive tumors.

PMID- 30198423
TI  - Guarana (Paullinia cupana Mart.) protects against amyloid-beta toxicity in
      Caenorhabditis elegans through heat shock protein response activation.
AB  - Alzheimer disease (AD) is a progressive neurodegenerative brain disorder that
      causes significant disruption in normal brain functioning, representing the most
      common cause of dementia in the elderly. The main hallmark of AD is the presence
      of amyloid plaques in the brain formed by the deposition of insoluble amyloid
      protein (Abeta) outside of neurons. Despite intensive investigation of the
      mechanisms of AD pathogenesis during the past three decades, little has been
      achieved in terms of effective treatments or ways to prevent the disease.
      Paullinia cupana, known as guarana, is a plant endemic to the Amazon region in
      Brazil with several beneficial effects reported, including delayed aging. In this
      study, we investigated the effects of chronic consumption of guarana ethanolic
      extract (GEE) on Abeta toxicity using a C. elegans model of AD. We analyzed the
      behavioral phenotype, oxidative damage and Abeta protein expression in worms
      treated with GEE. In addition, we investigated the possible role of the heat
      shock response on the beneficial effects induced by GEE. Overall, our data
      demonstrate that chronic GEE treatment decreased the formation of Abeta
      aggregates in C. elegans, preventing the behavioral deficits and the oxidative
      damage inducible by Abeta expression, due to activation of the heat shock protein
      (HSP) response. This finding provides a new alternative against amyloidogenic
      neurodegenerative diseases and other diseases caused by protein accumulation
      during aging.

PMID- 30198424
TI  - New CeF3-ZnO nanocomposites for self-lighted photodynamic therapy that block
      adenocarcinoma cell life cycle.
AB  - AIM: To synthesize and characterize the performances of a new all-inorganic
      nanocomposite (NC) for self-lighted photodynamic therapy against cancer. This NC
      could allow radiotherapy doses to be reduced, as it enhances the effects of x
      rays, generating cytotoxic reactive oxygen species as singlet oxygen. MATERIALS &
      METHODS: The proposed NC combines CeF3 and ZnO; CeF3 absorbs 6-MeV x-rays and
      activates the photosensitizer ZnO. Characterization is performed by transmission
      electron microscopy (TEM), scanning-TEM, energy dispersive x-ray spectrometry and
      fluorescence spectroscopies. Efficiency on human adenocarcinoma cells (A549) was
      tested by fluorescence spectroscopy, cytofluorimetry, viability assays,
      clonogenic assays, cell cycle progression assays. RESULTS: NC blocks A549's cell
      cycle before mitosis in the dark. Upon low-dose x-ray irradiation (2 Gy),
      reactive oxygen species/singlet oxygen are generated, further blocking cell cycle
      and reducing viability by 18% with respect to the sum of x-ray irradiation and NC
      dark activity. CONCLUSION: These novel NCs promise to reduce doses in
      radiotherapy, helping to reduce unwanted side effects.

PMID- 30198425
TI  - Mineralogical characterisation and magnetic separation of vanadium-bearing
      converter slag.
AB  - The recycling of metallic iron is commonly the first step to fully use the
      converter slag, which is the biggest waste discharge in the steelmaking process.
      This study presents a proposed improved process of separating metallic iron from
      vanadium-bearing converter slag more efficiently. The mineralogical and
      morphological characteristics of the converter slag were first investigated, and
      the results showed that most of the iron was incorporated in the spinel and
      olivine. Grinding, sieving and magnetic separation were combined to recover
      metallic iron from the converter slag, and yielded approximately 41.5% of iron in
      which the iron content was as high as 85%, and the non-magnetic concentrate
      contains 8.56% vanadium with a yield of 95.3% and 8.63% titanium with a yield of
      85.3%. The magnetic part can be used as the raw materials in the steel making
      process, whereas the non-magnetic part can be used as the raw materials for the
      further extraction of vanadium.

PMID- 30198426
TI  - Adsorption of naturals hormones estrone, 17beta-estradiol, and estriol by rice
      husk: monocomponent and multicomponent kinetics and equilibrium.
AB  - In the present study, the use of the rice husk biomass as an alternative
      biosorbent for treating the estrone, 17 beta-estradiol, and estriol hormones in
      monocomponent and multicomponent systems was investigated. The high-performance
      liquid chromatography technique (HPLC-UV) was applied in order to quantify the
      hormones, validating this method according to ANVISA and INMETRO. The biosorbent
      presented functional groups typical of cellulose, hemicellulose, lignin, and
      proteins, with an amorphous, fibrous, and porous surface. The best performance
      was obtained with a neutral pH and at room temperature (25[Formula: see text]C).
      The equilibrium times in batch systems were 60  min for the estrone, and 120 min
      for 17 betaestradiol and estriol. The monocomponent kinetics of adsorption of
      estrone and estriol were adequately described by the pseudo-first-order model,
      whereas for the 17 beta estradiol both pseudo-first-order and pseudo-second-order
      models well described the experimental data. For the multicomponent system, the
      kinetics of adsorption was appropriately represented by the pseudo-first-order
      model, demonstrating that the number of active sites was the limiting factor of
      the process. The monocomponent adsorption isotherms were adequately fitted by the
      Langmuir model, reaching adsorption capacities of 2.698, 1.649, and 0.979 mg g-1
      for the estrone, 17 betaestradiol, and estriol hormones, respectively. The
      ternary isotherm models did not represent the experimental data, indicating that
      there was no competition among the hormones. The reactions presented favourable
      and spontaneous characteristics. The rice husk biomass showed a great potential
      as an adsorbent when treating effluents contaminated with hormones.

PMID- 30198428
TI  - Diagnostics and Therapy of Human Diseases - Focus on Sialidases.
AB  - Sialic acid residues that make part of the cell surface repertoire of
      carbohydrate residues are implicated in various physiological processes and human
      pathologies. Sialidases, or neuraminidases, are the enzymes that are able to
      cleave and release the sialic acid residues, while trans-sialidases can transfer
      the residues from donor to acceptor molecules. They are important for processing
      the surface glycolipids and glycoproteins. Therapeutic potential of
      pharmacological sialidases inhibition is currently actively studied. Knowledge
      and expertise gained from genetic defects leading to human sialidase deficiency
      can be used for designing such drugs. In this review, we discuss the current
      progress in studying sialidases and their inhibitors and the relevance of these
      studies to developing novel therapeutic approaches. In vitro studies suggest that
      some sialidase inhibitors might be useful therapeutics for treating sialidosis,
      cancer, infections, immune diseases, atherosclerosis and other pathologies.
      Consequently, there is a field for further research and development. A thorough
      investigation of human sialidases is therefore crucial to human health.

PMID- 30198429
TI  - IGF-1 Gene Therapy as a Potentially Useful Therapy for Spontaneous Prolactinomas
      in Senile Rats.
AB  - BACKGROUND: Insulin-like Growth Factor1 (IGF1) is a powerful neuroprotective
      molecule. We have previously shown that short-term hypothalamic IGF1 gene therapy
      restores tuberoinfundibular dopaminergic neuron function in aging female rats.
      OBJECTIVE: Our aim was to implement long-term IGF-I gene therapy in pituitary
      prolactinomas in senile female rats. METHODS: Here, we assessed the long-term
      effect of IGF1 gene therapy in the hypothalamus of young (4 mo.) and aging (24
      mo.) female rats carrying spontaneous pituitary prolactinomas. We constructed and
      injected a Helper-Dependent (HD) adenovector expressing the gene for rat IGF1 or
      the reporter red fluorescent protein DsRed. Ninety-one days post vector
      injection, all rats were sacrificed and their brains and pituitaries fixed. Serum
      prolactin (PRL), Estrogen (E2) and progesterone (P4), as well as hypothalamic
      IGF1 content, were measured by RIA. Anterior pituitaries were immunostained with
      an anti-rat PRL antibody and submitted to morphometric analysis. RESULTS: DsRed
      expression in the Mediobasal Hypothalamus (MBH) was strong after the treatment in
      the DsRed group while IGF1 content in the MBH was higher in the IGF1 group. The
      IGF1 treatment affected neither pituitary weight nor PRL, E2 or P4 serum levels
      in the young rats. In the old rats, IGF1 gene therapy reduced gland weight as
      compared with intact counterparts and tended to reduce PRL levels as compared
      with intact counterparts. The treatment significantly rescued the phenotype of
      the lactotropic cell population in the senile adenomas. CONCLUSION: We conclude
      that long-term hypothalamic IGF1 gene therapy is effective to rescue spontaneous
      prolactinomas in aging female rats.

PMID- 30198430
TI  - Aging and Proteins: What Does Proteostasis Have to Do with Age?
AB  - The world is aging and we must face the challenges that this brings. One of the
      reasons for the increasing aging of the world's population is the increase in
      life expectancy and, since we live longer, it is of paramount importance to live
      well and to prevent age-associated diseases. In this way, it is crucial to
      improve knowledge of the aging process and of the mechanisms that contribute to
      it. Ideally it would be of great interest to have a panel of biomarkers of
      healthy aging that would allow an estimate of the biological age of an
      individual. One of the changes that greatly contribute to aging is the loss of
      protein homeostasis, also called proteostasis. To ensure the proper function of
      cells and to maintain cellular proteostasis, organisms have developed systems to
      control protein synthesis, folding and degradation. Loss or dysfunction of
      proteostasis is at the root of many well-studied human neurological diseases,
      such as Alzheimer's disease and, more recently, it has been implicated in the
      aging process with some reports showing long-lived animals to have improved
      proteostasis. Growing evidence suggests a strong link between modifications in
      the quantity and/or activity of several players involved in proteostasis and
      longevity. In this review, we give an overview of the main characteristics of
      aging with focus on proteostasis. We present how changes in components of
      proteostasis, during aging, impact the lifespan of model organisms. We also
      briefly review the current state of aging biomarkers and discuss the potential of
      proteostasis network components as markers of healthy aging.

PMID- 30198431
TI  - MicroRNAs in the Intestine: Role in Renewal, Homeostasis, and Inflammation.
AB  - The mammalian intestine is not only an organ for food digestion and nutrient
      absorption but also an integral part of the immune and endocrine systems. The
      intestinal epithelium under stressful environments requires epithelial cells to
      rapidly elicit changes in gene expression patterns to regulate their survival,
      adapt to stress, and maintain epithelial homeostasis. Recently, miRNAs have
      emerged as a novel class of posttranscriptional gene regulators that are
      fundamentally involved in many aspects of intestinal epithelial differentiation,
      architecture, and barrier function. In this review, we highlight the critical
      roles of miRNAs in both the crypt-villus axis of cellular self-renewal and
      inflammation in the mammalian intestinal mucosa and their impact on the
      microbiota. We also discuss the functions of specific miRNAs within the intestine
      to better understand the cellular mechanisms that promote intestinal homeostasis,
      and the influence of dietary components in the regulation of endogenous miRNA in
      the study of nutrition and gene regulation in intestinal health.

PMID- 30198432
TI  - miR-142-3p Inhibits the Metastasis of Hepatocellular Carcinoma Cells by
      Regulating HMGB1 Gene Expression.
AB  - BACKGROUND: Non-coding small RNAs are involved in organism development, and their
      aberrant regulation induces various diseases, including hepatocellular carcinoma
      (HCC), but their exact mechanisms have not been determined. OBJECTIVE: The aim
      was to investigate the role of miR-142-3p on HMGB1 expression in hepatocellular
      carcinoma. METHODS: Expression levels of miR-142-3p in HCC tissues and cultured
      cells were measured by RT-PCR. The invasion and metastasis abilities of HepG2
      cells according to Transwell migration and invasion assays, and protein
      expression was measured by western blotting. RESULTS: The present study reported
      that miR-142-3p promotes the invasion and migration of HCC cells. miR-142-3p
      levels are lower in HCC tissues than in adjacent non-cancerous tissues,
      suggesting a tumor suppressor role for miR-142-3p. Highmobility group box protein
      1 (HMGB1) is an oncogene that promotes the metastasis of HCC. miR-142-3p or HMGB1
      knockdown alone inhibits the invasion and migration of HCC cells, and HMGB1
      overexpression impedes the effect of miR-142-3p. Further studies showed that
      HMGB1 is a direct target gene of miR-142-3p in HCC. miR-142-3p represses HMGB1
      gene transcription by directly binding to the 3' untranslated region (UTR) of
      HMGB1, thereby inhibiting cancer cell invasion and migration. CONCLUSION: This
      study, for the first time, reports that miR-142-3p is a novel tumor suppressor
      that inhibits the invasion and migration of HCC cells by directly regulating gene
      transcription of HMGB1. Thus, miR-142-3p may be a potential diagnostic and
      therapeutic biomarker for HCC patients.

PMID- 30198433
TI  - An Antioxidant Role by Minocycline Via Enhancing the Activation of LKB1/AMPK
      Signaling in the Process of Cerebral Ischemia Injury.
AB  - BACKGROUND: LKB1/AMPK signaling pathway, as a metabolic checkpoint, is involved
      in the pathogenesis of cerebral ischemia injury. Minocycline, a tetracycline
      derivative, protects against cerebral ischemia via reducing inflammation,
      oxidative stress, and apoptosis. The aim of the study was to evaluate the
      influence of minocycline on oxidative biomarkers and LKB1/AMPK signaling pathway
      in Wistar rats with focal cerebral ischemia injury and to clarify the
      neuroprotective mechanism of minocycline against focal cerebral ischemia injury.
      METHODS: The focal cerebral ischemia injury of Wistar rats was established by
      inserting a thread into the left middle cerebral artery. 2,3,5
      Triphenyltetrazolium chloride (TTC) staining was used to label infarct volume.
      The levels of MDA and LPO were measured with a biochemical assay. All other items
      were determined by Western blotting. RESULTS: Minocycline decreased cerebral
      infarct volume, but had no effects on neurological scores. Minocycline improved
      the biological activity of GPx-1/2, GSS and GR, while limited the GGT1 activity
      in the hippocampus of cerebral ischemia-reperfusion rats. Minocycline also
      elevated the biological activity of SOD and counteracted lipid peroxidation.
      Minocycline enhanced the activity of both LKB1 and the levels of the three AMPK
      subunits in the hippocampus of cerebral ischemia-reperfusion rats. CONCLUSION:
      Minocycline effectively inhibits oxidative stress via modulating antioxidative
      enzymes and activating the LKB1/AMPK signaling pathway in the process of acute
      cerebral infarct.

PMID- 30198434
TI  - Seven Novel and Three Known Mutations in FOXL2 in 10 Chinese Families with
      Blepharophimosis Syndrome.
AB  - BACKGROUND: Blepharophimosis syndrome (BPES) is characterized by eyelid
      malformation with occasional premature ovarian failure. Mutations in FOXL2
      underlie a fraction of BPES cases. OBJECTIVE: We aimed to investigate the genetic
      basis of BPES in 26 Chinese families that included 78 patients. METHODS: We
      performed ophthalmological examinations on each family member. We used Sanger
      sequencing to screen FOXL2 exons and their flanking sequences. We also performed
      bioinformatics studies, structural modeling and pathogenicity evaluations on all
      identified variations. Literature was reviewed and genotype-phenotype correlation
      analysis was performed. RESULTS: The patients had typical manifestations of BPES.
      Ten mutations were identified in ten of the twenty-six families. Among these,
      seven were novel mutations. These included the six truncating mutations,
      p.Glu69*, p.Gly256Glyfs*14, p.Ala14Serfs*135, p.Pro333Profs*200,
      p.Pro290Leufs*70, and p.Pro157Profs*91, and one missense mutation, p.Tyr59Cys.
      The mutations were scattered within the gene, and no mutational hotspots were
      found. Genotype-phenotype correlation analysis showed that frameshift or nonsense
      mutations were correlated with type I BPES, while in-frame or missense mutations
      were associated with type II BPES. CONCLUSION: We report the largest BPES cohort
      in China thus far as well as seven novel mutations in FOXL2. The identification
      of novel mutations has not only expanded the mutational spectrum of the gene
      (which is valuable for mutation detection-based screening) but also suggests that
      most mutations within the Chinese population may not have been characterized yet.

PMID- 30198435
TI  - On the Structure and Transdermal Profile of Liquid Crystals Based on Phytantriol.
AB  - BACKGROUND: There has been a growing concern in transdermal drug technology over
      the past several decades. As a novel transdermal delivery system, Lyotropic
      liquid crystals (LLC) still face challenges such as drug loading, limited drug
      permeation and instability of systems. LLC system is so sensitive that a very
      subtle change in composition may induce a phase transformation or conversion of
      spatial configuration, and result in a diverse percutaneous delivery
      subsequently. OBJECTIVE: To find out the effects of hydrophilic and lipophilic
      components on the structure and transdermal properties of LLCs, hydrophilic
      sinomenine hydrochloride (SH) and lipophilic cinnamaldehyde (CA) was chosen as a
      model drug and a skin permeation enhancer, respectively, several formulations
      were prepared and compared. METHOD: The structure of LLC was evaluated by visual
      observation, Cross-polarizing light microscopy (CPLM) and Small angle X-ray
      diffraction (SAXS). The Franz diffusion cell was applied to investigate its skin
      penetration of SH across the rat skins. Fourier transform infrared spectroscopy
      (FTIR) was recorded to evaluate the intermolecular interaction between the LC
      samples and stratum corneum (SC). CONCLUSION: The results showed that a
      controlled transdermal process might be obtained by adjusting the ratios of
      different drugs or loading doses when LLCs with dual-components were applied.

PMID- 30198436
TI  - Assessment of Transmitted HIV-1 Drug Resistance Mutations Using Ultra- Deep
      Pyrosequencing in a Turkish Cohort.
AB  - BACKGROUND: Antiretroviral treatment (ART) reduces morbidity and mortality caused
      by human immunodeficiency virus (HIV) infection; however, the emergence of drug
      resistant strains poses an important obstacle to treatment success. Using
      conventional sequencing methods to determine antiretroviral resistance, mutations
      present in >=20% of quasispecies can be identified, but drug-resistant minority
      variants can lead to virologic failure. OBJECTIVE: We aimed to assess transmitted
      drug resistance mutations (TDRMs) within minority variants using ultra-deep
      pyrosequencing (UDPS). METHOD: Treatment-naive adult patients were included in
      this observational study. Surveillance TDRMs were classified as >=20% or at
      minority variant level (>=2% - <20%). Genotypic sensitivity score calculated by
      using all pre-treatment drug resistance mutations (PDRMs) was also evaluated.
      RESULTS: Thirty-six patients were analyzed. Any TDRM at >=20% level was detected
      in 8.3% of the patients (n=3). This prevalence increased to 30.6% (n=11) with the
      inclusion of minority variants. All non-nucleoside reverse transcriptase
      inhibitor and protease inhibitor-related TDRMs were within minority variants. The
      genotypic sensitivity score of rilpivirine-based regimens was considerably
      diminished when minority variants were included in the PDRM analysis. CONCLUSION:
      UDPS was used for the first time to assess TDRM in a Turkish HIV cohort and
      uncovered several mutations hidden within minority variants. UDPS may be
      preferred to detect PDRMs for avoiding virologic failure with rilpivirine-based
      ART regimens.

PMID- 30198437
TI  - Similarities and Differences Between Carotid Artery and Coronary Artery Function.
AB  - BACKGROUND: Cardiovascular Disease (CVD) remains one of the leading causes of
      morbidity and mortality. Strategies to predict development of CVD are therefore
      key in preventing and managing CVD. One stratergy in predicting CVD is by
      examining the role of traditional risk factors for CVD (e.g. age, sex, weight,
      blood pressure, blood lipids, blood glucose, smoking and physical activity).
      Although these measures are non-invasive and simple to perform, they provide
      limited information of CVD prediction. Directly examining functional
      characteristics of arteries that are involved in the pathophysiological changes
      that contribute to the development of CVD improve prediction of future CVD.
      Nevertheless, examining the function of arteries susceptible to atherosclortic
      changes, such as the coronary arteries, is invasive, expensive, and associated
      with high risk for complications. More accessible arteries can be used as a
      surrogate measure of coronary artery function. For example, the carotid artery
      may be a superior surrogate measure of coronary artery function given that, the
      carotid artery represents a central vessel that shows similarities in vasomotor
      function and anatomical structure with coronary arteries. CONCLUSION: This review
      summarises the similarities between the carotid and coronary arteries, describes
      how both arteries respond to specific vasoactive stimuli, and discusses if the
      easily assessible carotid artery can provide information about vascular function
      (e.g. vasomotor reactivity to sympathetic stimulation) which is prognostic for
      future cardiovascular events. Finally, the impact of older age and lifestyle
      interventions (e.g. exercise training) on carotid artery function will be
      discussed.

PMID- 30198438
TI  - A Concise History of Thiopurines for Inflammatory Bowel Disease: from Anecdotal
      Reporting to Treat-to-Target Algorithms.
AB  - BACKGROUND: The need for immune suppressive strategies in the control of chronic
      inflammatory bowel diseases originated in the 1960s following the perception of a
      relative inefficacy of salazopyrin and its derivatives. In some 50 years upon an
      anecdotal claim, the indication for thiopurines in the management of inflammatory
      bowel diseases has come of age. OBJECTIVE: The aim of this minireview is to give
      an overview, after the historical premises, of the current use of thiopurines in
      the context of inflammatory bowel diseases. METHOD: Through MEDLINE searches, we
      reviewed the literature of the last two decades. RESULTS: For Crohn's disease,
      the 1980 trial of 6-mercaptopurine for steroid sparing and fistula closure proved
      pivotal. The analysis of withdrawal experiments and of numerous open trials have
      established the efficacy of thiopurines for ulcerative colitis. In this
      indication, cutting-edge data are now showing that because targeting dysplasia,
      thiopurines can induce mucosal/histological healing, thus abolishing or delaying
      the need for pre-emptive (tumor prophylactic) colectomy. CONCLUSION: In UC
      thiopurines may be recognized to effect a treat-to-target strategy, joining the
      modern algorithms of rheumatologic disorders.

PMID- 30198439
TI  - Immunotherapy in Patients with Recurrent and Metastatic Squamous Cell Carcinoma
      of the Head and Neck.
AB  - Head and neck squamous cell carcinoma (HNSCC) is the most common malignant cancer
      occurring in the head and neck area, approximately 90% of the cases. Even in the
      cases of primary radical treatment (surgical, concomitant chemoradiotherapy or
      radiotherapy alone), local recurrence or distal metastases are often observed. In
      patients with recurrent disease who are unable to receive radical treatment, the
      results of palliative chemotherapy are not satisfactory. The breakthrough in the
      therapy of advanced HNSCC was the approval of cetuximab in combination with
      chemotherapy in 2008. However, for almost a decade we have seen many negative
      studies with new treatment approaches including various types of molecules
      targeting epidermal growth factor receptors or vascular endothelial growth factor
      receptors, as well as different cytokines or cancer vaccines. Recently two new
      agents have been approved in the treatment of recurrent or metastatic HNSCC.
      These are immune-checkpoint inhibitors targeting PD1 (nivolumab and
      pembrolizumab) expressed mainly on T-cells. However, the results remain
      unsatisfactory - most of the patients do not respond to the treatment and some of
      the responding patients develop further progression. Many phase 3 studies are
      currently ongoing evaluating the efficacy of combinational treatment - anti-CTLA4
      with anti-PD1 or anti-PD-L1. Very encouraging results have been shown in early
      phase studies evaluating the combination of immune-checkpoint inhibitors with
      tumor microenvironment immunosuppressive inhibitors. Undoubtedly, further
      research in the field of biomarkers for effective immunotherapy is needed in
      order to select a group of patients whose will benefit from this therapy, as the
      treatment is still ineffective in most patients.

PMID- 30198440
TI  - A Comparison of the Inhibitory Effects of Anti-Cancer Drugs on Thioredoxin
      Reductase and Glutathione S-Transferase in Rat Liver.
AB  - BACKGROUND: While thioredoxin reductase (TrxR) plays an important role in
      regulation of the intracellular redox balance and various signalling pathways,
      glutathione S-transferase (GSTs) enzymes belong to the detoxification family that
      catalyse the conjugation of glutathione with various endogenous and xenobiotic
      electrophiles. Since TrxR and GSTs are overexpressed in many cancer cells, they
      have been identified as potential targets to develop chemotherapeutic strategies.
      METHOD: The mitochondrial TrxR (TrxR2) enzyme and the cytosolic GST enzyme was
      purified from rat liver via affinity chromatography. After the purification, the
      in vitro inhibition effects of some anticancer drugs (cisplatin, calcium
      folinate, carboplatin, epirubicin hydrochloride, doxorubicin hydrochloride,
      paclitaxel, etoposide, fluorouracil, and methotrexate) were investigated on both
      enzymes. Since only methotrexate inhibits both enzymes among all the anticancer
      drugs, a molecular docking study was performed to determine the binding site and
      the binding affinity of methotrexate to the enzymes. RESULTS: Firstly, TrxR2 and
      GST were found to have a specific activity of 0.436, 1765 EU/mg proteins with a
      yield of 39.20%, 31.28% and 207.6, 3516.6 of purification fold, respectively.
      While TrxR2 was strongly inhibited by all of the anticancer drugs, GST was not
      inhibited by any of the anticancer drugs except methotrexate. CONCLUSION: Both
      enzymes were inhibited by only methotrexate in rat liver, and methotrexate was
      well placed in the active sites of both proteins. Therefore, it may be argued
      that methotrexate may be a more effective anticancer drug than all other drugs
      used in this study against the multi drug resistance that will occur during
      chemotherapy.

PMID- 30198441
TI  - Chlorambucil Cytotoxicity Reduction In Rats Through Bone Marrow, An In Vivo
      Study.
AB  - Bone marrow [BM] have self-renovationcapacity and have been used recently in
      tumor medicine.Chlorambucil[CHB] is ordinarily utilized chemotherapy to treat
      varietiesof malignancy patients. This investigation intended to gauge the
      effectiveness of BM as an invivoantimutagenicagainst CHB.The experimental design
      relies upon four classes, each class contains ten adult male albino rats as
      follows: control, rats infused orally with CHB for fourteen days, rats
      intravenously infused with BM through a tail vein one time, rats infused the mix
      of CHB and BM. The Anticancer capability of BM was assessed by cytogenetic assay
      and mitotic index. The declarations of the apoptosis-related genes were examined
      by RT-qPCR examination. The present study demonstrated a curative effect of BM
      against thecytotoxic impact of CHB. Infusion of BM after chemotherapy help to
      diminish the chromosomal aberration, increment mitotic index and decline the
      Bax/Bcl2 proportion compared with[CHB] class gather that prompts expanding the
      survival rate of influenced cells with chemotherapy cytotoxicity.

PMID- 30198442
TI  - Synthesis and biological evaluation of novel 2-(4-acetyl-3-methyl-5-(arylamino)
      thiophen-2-yl)-3-arylquinazolin-4(3H)-one derivatives as potential anti
      inflammatory and antioxidant agents.
AB  - BACKGROUND: A new series of 2-(4-acetyl-3-methyl-5-(arylamino) thiophen-2-yl)-3
      arylquinazolin-4(3H)-one derivatives (11a-11j) were synthesized from acetyl
      acetone, phenyl isothiocyanate and 2-chloromethyl quinazolinone. OBJECTIVE: Due
      to side effects of Non Steroidal anti-inflammatory drugs (NSAID), an attempt was
      made to identify novel tetrasubstituted thiophene lead compound as potential anti
      inflammatory and antioxidant agent. METHODS: Then newly synthesized compounds
      were characterized by IR spectroscopy, 1H NMR and mass spectrometry. The
      synthesized compounds were screened for their in vivo anti-inflammatory activity
      in carrageenan induced rat hind paw edema model at dose 20mg/kg body weight using
      diclofenac sodium as a standard drug. The compounds were also evaluated for their
      in vitro DPPH free radical-scavenging activity and nitric oxide radical
      scavenging activity at the concentrations of 10, 20, 40, 60, 80 and 100 ug/mL
      using ascorbic acid as standard drug. RESULTS: The results from carrageenan
      induced rat hind paw edema showed that compounds 11e, 11f and 11b show a
      significant anti-inflammatory activity of 46.61 %, 48.94 % and 47.04 % protection
      respectively to inflamed paw but less than diclofenac sodium. Compounds 11h and
      11e show good DPPH free radical scavenging and nitric oxide radical scavenging
      activity respectively. CONCLUSION: From results it was observed that highly
      substituted thiophene scaffold exhibits anti-inflammatory and antioxidant
      activity.

PMID- 30198443
TI  - Antiallergy drugs as potent inhibitors of lipase with structure-activity
      Relationships and molecular docking.
AB  - BACKGROUND: Inhibition activity of 8 synthetic molecules known as anti-allergy
      drugs on lipases have been investigated. The enzymatic inhibition produced by
      these molecules is described here for the first time. OBJECTIVE: The used anti
      allergy drugs are: loratidine, primalan, zyrtec, histagan, periactin, ketotifene,
      rifex and bilastine. METHODS: lipase inhibition is studied using
      spectrophotometric method. Molecular docking has been achieved for the first time
      for these drugs using AutoDock Vina program to discuss the nature of
      interactions, structure activity relationship and the mechanism of inhibition.
      RESULTS: The biological evaluation of these molecules showed that most of these
      drugs are potent lipase inhibitors with competitive type inhibition. The best
      drug is loratidine with IC50=0.44mg/ml and Ki=0.86 mM and competitive type
      inhibition. Molecular docking studies of the studied molecules confirmed their
      competitive inhibitory type with their binding to the catalytic active site (CAS)
      of lipases. CONCLUSION: Hence, these drugs could be used for obesity or
      candidiasis treatment taking advantage of the much known details of their
      secondary effects as antiallergy drugs.

PMID- 30198444
TI  - Natural Phenolics as Inhibitors of the Human Neutrophil Elastase (HNE) Release:
      An Overview of Natural Anti-inflammatory Discoveries during Recent Years.
AB  - Serine protease, human neutrophil elastase (HNE), has been shown to be useful in
      medical science, however, its over production and malfunctioning may produce
      devastating effects and cause serious damage to the host. Unfortunately, the
      present approved drug, sivelestat, only alleviates the symptoms of the diseases
      caused by malfunction of HNE but not the disease progression. Therefore, there is
      crucial need to search potent and safer molecules as elastase inhibitors and to
      develop better anti-inflammatory drugs in future. In addition, Nature is the best
      architect that may provide a safer future drug candidate as HNE
      production/activity inhibitor. Since phenolic natural products are already known
      as anti-inflammatory compounds, either by acting as antioxidants or by any other
      mechanism, thus, this review article summarizes the discovery and elastase
      inhibitory activity of ?180 phenolics isolated from diverse natural sources
      during more than one decade, i.e. 2005-2017.

PMID- 30198445
TI  - Parathyroid Carcinoma Causing Mild Hyperparathyroidism in Neurofibromatosis Type
      1: A Case Report and Systematic Review.
AB  - BACKGROUND: Neurofibromatosis type 1 is an autosomal dominant disorder
      characterized by an increased incidence of tumors, including endocrine ones.
      Primary hyperparathyroidism can be rarely caused by a parathyroid carcinoma;
      these patients are generally characterized by severe symptoms, large neck lesions
      and high levels of PTH and calcium. We report a case of hyperparathyroidism due
      to parathyroid carcinoma in a patient affected by neurofibromatosis type 1. A
      systematic review of literature was also conducted. PATIENT FINDINGS: A 56-year
      old woman was referred for a 13 mm-nodular lesion of the neck incidentally
      discovered on ultrasound examination and mild hyperparathyroidism. A 99mTc
      tetrofosmin/pertechnetate subtraction scintigraphy was negative for parathyroid
      disease. Given the absence of suspicious ultrasound finding, a fine-needle
      aspiration cytology was performed with iPTH determination in the aspirate,
      confirming the parathyroid origin of the lesion. The patient underwent left
      inferior parathyroidectomy with intraoperative monitoring of iPTH and became
      normocalcemic. On histopathological examination, parathyroid carcinoma presenting
      at the resection margin was diagnosed, thus a surgery revision was requested.
      CONCLUSION: Even if literature does not support a syndromic association between
      neurofibromatosis type 1 and primary hyperparathyroidism, the benefit of
      precociously diagnosing and treating this condition may outweigh costs associated
      with screening. This case report moreover demonstrates that sometimes clinical,
      laboratory and imaging aspects suspicious for cancer may be missing. A prompt
      referral to a high-volume center is crucial for the management of those cases of
      incidental histopathological diagnosis.

PMID- 30198446
TI  - Zenker Diverticulum: A Potential Pitfall in Thyroid Ultrasound Evaluation: A Case
      Report and Systematic Review of Literature.
AB  - BACKGROUND AND OBJECTIVE: Zenker diverticulum (ZD) can sometimes be
      misinterpreted as a thyroid nodule both at clinical evaluation and at ultrasound
      (US). CASE PRESENTATION: We reported the case of a 46-years-old woman complaining
      of a lump in the anterior left aspect of the neck. Following clinical examination
      and US evaluation, a thyroid nodule was initially diagnosed and the patient was
      referred to our institution to be submitted to a fine-needle aspiration cytology.
      Management and Outcome: A ZD was suspected by US and diagnosed by gastrografin
      esophagram, thus an endoscopic diverticulotomy was requested. CONCLUSION: A
      correct US evaluation can be crucial for the appropriate management of a neck
      mass.

PMID- 30198447
TI  - Heart rate variability during a cognitive reappraisal task in female patients
      with borderline personality disorder: the role of comorbid posttraumatic stress
      disorder and dissociation.
AB  - BACKGROUND: Emotion dysregulation is a core feature of borderline personality
      disorder (BPD), which often co-occurs with posttraumatic stress disorder (PTSD).
      Difficulties in emotion regulation (ER) have been linked to lower high-frequency
      heart rate variability (HF-HRV), a measure of autonomous nervous system
      functioning. However, previous research on vagally-mediated heart rate in BPD
      revealed heterogeneous findings and the effects of comorbid PTSD and dissociation
      on HF-HRV are not yet completely understood. This study aim to investigate HF-HRV
      during resting-state and an ER task in female BPD patients with comorbid PTSD
      (BPD + PTSD), patients without this comorbidity (BPD), and healthy controls (HC).
      METHODS: 57 BPD patients (BPD: n = 37, BPD + PTSD: n = 20) and 27 HC performed an
      ER task with neutral, positive, and negative images. Participants were instructed
      to either attend these pictures or to down-regulate their upcoming emotions using
      cognitive reappraisal. Subjective arousal and wellbeing, self-reported
      dissociation, and electrocardiogram data were assessed. RESULTS: Independent of
      ER instruction and picture valence, both patient groups (BPD and BPD + PTSD)
      reported higher subjective arousal and lower wellbeing; patients with BPD + PTSD
      further exhibited significantly lower HF-HRV compared with the other groups.
      Higher self-reported state dissociation predicted higher HF-HRV during down
      regulating v. attending negative pictures in BPD + PTSD. CONCLUSIONS: Findings
      suggest increased emotional reactivity to negative, positive, and neutral
      pictures, but do not provide evidence for deficits in instructed ER in BPD.
      Reduced HF-HRV appears to be particularly linked to comorbid PTSD, while
      dissociation may underlie attempts to increase ER and HF-HRV in BPD patients with
      this comorbidity.

PMID- 30198448
TI  - Therapy for fatigue and cognitive dysfunction in postural orthostatic tachycardia
      syndrome.
AB  - IntroductionSevere fatigue and cognitive dysfunction are frequent symptoms in
      patients with postural orthostatic tachycardia syndrome. They can be
      debilitating, and often do not resolve despite improvement in haemodynamic
      symptoms. Our analysis was intended to assess clinical outcomes of medication
      treatment for these symptoms in a large, single-centre paediatric
      programme.Materials and MethodsWe performed a retrospective review of patients
      treated for fatigue and cognitive dysfunction. Patients aged 18 years or younger
      at the time of initial diagnosis were included. Patients who had a specific
      medication ordered five or more times for these symptoms were confirmed by chart
      review for clinical improvement. Percentage of patients with clinical improvement
      for each medication and overall for all medications, as well as the number of
      medications per patient required to achieve improvement, were assessed. Data were
      analysed based on gender as well. t-Test and chi2 analyses were used to assess
      for differences between means in variables, or specific variables. RESULTS: A
      total of 708 patients met study criteria, of whom 517 were treated for fatigue or
      brain fog. Overall efficacy was 68.8%, with individual medication effectiveness
      ranging from 53.1 (methylphenidate) to 16.5% (atomoxetine). There was no
      significant difference in efficacy with respect to gender. The median number of
      medications used per patient was 2, without gender difference. Therapy was
      limited by side effects or lack of efficacy.DiscussionMedications are effective
      in the improvement of fatigue and cognitive dysfunction in these patients.
      However, trials of multiple medications may be needed before achieving clinical
      improvement.

PMID- 30198449
TI  - Variability in paediatric cardiac postoperative chest tube management.
AB  - Limited evidence exists to guide chest tube management following cardiac surgery
      in children. We assessed chest tube practice variation by surveying paediatric
      heart centres to prepare for a multi-site quality improvement project. We
      summarised management strategies highlighting variability in criteria for chest
      tube removal between and within centres. This lack of standardisation provides an
      opportunity for quality improvement.

PMID- 30198450
TI  - Examining the Attitudes and Knowledge of Social Work and Nursing Students on
      Later-Life Sexuality.
AB  - ABSTRACTWe examined ageist beliefs, attitudes, and knowledge towards sexuality in
      later life among 148 nursing students and 137 social work students in their first
      year of studies. The students completed the Fraboni Scale of Ageism, the
      Attitudes and Knowledge towards Older Adults' Sexuality Scale, and questionnaires
      regarding contact with older adults, prior sexual education, and socio
      demographics. The results indicated that nursing students have more conservative
      attitudes towards older adults' sexuality. Ageist beliefs correlated positively
      with more conservative attitudes towards older adults' sexuality. These
      conservative attitudes 'were negatively correlated with knowledge about sexuality
      in later life. Older students have more knowledge about sexuality in later life
      and more permissive attitudes towards older adults' sexuality. Religious students
      have less knowledge, and more conservative attitudes, towards older adults'
      sexuality. Previous sexual education was not associated with the students'
      attitudes and knowledge towards older adults' sexuality. Implications for
      designing continuing education programs are discussed.

PMID- 30198451
TI  - Virtual reality as a distraction technique for pain and anxiety among patients
      with breast cancer: A randomized control trial.
AB  - OBJECTIVE: The goal of this study was to assess the effectiveness of immersive
      virtual reality (VR) distraction technology in reducing pain and anxiety among
      female patients with breast cancer. METHOD: A randomized control trial design was
      used with a sample of 80 female patients with breast cancer at a specialized
      cancer center in Jordan. Participants were randomly assigned into intervention
      and comparison groups.ResultThe study findings showed that one session of the
      immersive VR plus morphine made a significant reduction in pain and anxiety self
      reported scores, compared with morphine alone, in breast cancer
      patients.Significance of resultsImmersive VR is an effective distraction
      intervention for managing pain and anxiety among breast cancer patients. Using
      immersive VR as an adjuvant intervention is more effective than morphine alone in
      relieving pain and anxiety; furthermore, VR is a safe intervention more than
      pharmacological treatment.

PMID- 30198452
TI  - Antimalarial bednet protection of children disappears when shared by three or
      more people in a high transmission setting of western Kenya.
AB  - A sizeable proportion of households is forced to share single long-lasting
      insecticide treated net (LLIN). However, the relationship between increasing
      numbers of people sharing a net and the risk for Plasmodium infection is unclear.
      This study revealed whether risk for Plasmodium falciparum infection is
      associated with the number of people sharing a LLIN in a holoendemic area of
      Kenya. Children ?5 years of age were tested for P. falciparum infection using
      polymerase chain reaction. Of 558 children surveyed, 293 (52.5%) tested positive
      for parasitaemia. Four hundred and fifty-eight (82.1%) reported sleeping under a
      LLIN. Of those, the number of people sharing a net with the sampled child ranged
      from 1 to 5 (median = 2). Children using a net alone or with one other person
      were at lower risk than non-users (OR = 0.29, 95% CI 0.10-0.82 and OR = 0.47, 95%
      CI 0.22-0.97, respectively). On the other hand, there was no significant
      difference between non-users and children sharing a net with two (OR = 0.88, 95%
      CI 0.44-1.77) or more other persons (OR = 0.75, 95% CI 0.32-1.72). LLINs are
      effective in protecting against Plasmodium infection in children when used alone
      or with one other person compared with not using them. Public health
      professionals should inform caretakers of the risks of too many people sharing a
      net.

PMID- 30198454
TI  - Thoracic endovascular aortic repair of a late aortic aneurysm after patch repair
      of an interrupted aortic arch.
AB  - We reported a successful case of thoracic endovascular aortic repair of a late
      aortic aneurysm after patch repair of an interrupted aortic arch and favourable
      outcome 4 years after the procedure.

PMID- 30198453
TI  - Lack of access to paediatric cardiology services in the public health system in
      four major urban centres in Peru.
AB  - For one-third of the Peruvian population living in large cities outside the
      capital city Lima, there is no access to paediatric cardiology services provided
      by the public health care system. Children with suspected CHD living in these
      areas are referred to the adult cardiologist working at the regional hospitals
      for care and treatment. This is a consequence of the universal health care system
      and the heavily skewed distribution of the health care workforce towards the
      capital city of Lima. This imbalance has resulted in a severe shortage of
      paediatric cardiologists practicing outside of Lima and the adult cardiologists
      that remain are left to make up for this deficit.To gain a better understanding
      of the current model of care for children with suspected CHD within the public
      health care system in Peru, we surveyed adult cardiologists from four major urban
      centres that serve one-third of the Peruvian population outside of Lima. We
      determined that adult cardiologists spend a significant amount of time treating
      children, but lack the specialised training and equipment to provide model care.
      The cardiologists indicated that receiving additional training and appropriate
      equipment would help enable them to provide proper care for these children.

PMID- 30198455
TI  - The protein-sparing effect of alpha-lipoic acid in juvenile grass carp,
      Ctenopharyngodon idellus: effects on lipolysis, fatty acid beta-oxidation and
      protein synthesis.
AB  - To investigate the protein-sparing effect of alpha-lipoic acid (LA), experimental
      fish (initial body weight: 18.99 (sd 1.82) g) were fed on a 0, 600 or 1200 mg/kg
      alpha-LA diet for 56 d, and hepatocytes were treated with 20 MUm compound C, the
      inhibitor of AMP kinase alpha (AMPKalpha), treated for 30 min before alpha-LA
      treatment for 24 h. LA significantly decreased lipid content of the whole body
      and other tissues (P0.05). Consistent with results from the experiment in vitro,
      LA activated phosphorylation of AMPKalpha and notably increased the protein
      content of adipose TAG lipase in intraperitoneal fat, hepatopancreas and muscle
      in vivo (P<0.05). Meanwhile, LA significantly up-regulated the mRNA expression of
      genes involved in fatty acid beta-oxidation in the same three areas, and LA also
      obviously down-regulated the mRNA expression of genes involved in amino acid
      catabolism in muscle (P<0.05). Besides, it was observed that LA significantly
      activated the mammalian target of rapamycin (mTOR) pathway in muscle of
      experimental fish (P<0.05). LA could promote lipolysis and fatty acid beta
      oxidation via increasing energy supply from lipid catabolism, and then, it could
      economise on the protein from energy production to increase protein deposition in
      grass carp. Besides, LA might directly promote protein synthesis through
      activating the mTOR pathway.

PMID- 30198456
TI  - Impact of age at bidirectional cavopulmonary anastomosis on haemodynamics after
      Fontan operation.
AB  - : BackgroundsThe aim of this study was to assess the impact of age at
      bidirectional cavopulmonary anastomosis on haemodynamics after total
      cavopulmonary connection. METHODS: We conducted a retrospective analysis of 100
      consecutive patients who underwent total cavopulmonary connection from 2010 to
      2014. All patients had previously undergone bidirectional cavopulmonary
      anastomosis. These patients were classified into two groups according to age at
      bidirectional cavopulmonary anastomosis: younger group, 6 months (n=67). RESULTS:
      The proportion of hypoplastic left heart syndrome was higher in the younger group
      (48 versus 4%). After total cavopulmonary connection, the chest tube period was
      longer in the younger group (10.1+/-6.6 versus 6.7+/-4.5 days; p=0.009).
      Catheterisation 6 months after total cavopulmonary connection revealed that
      pulmonary artery pressure was higher (11.5+/-1.9 versus 10.4+/-2.1 mmHg; p=0.017)
      and Nakata index was lower (219+/-79 versus 256+/-70 mm2/m2; p=0.024) in the
      younger group. In patients with a non-hypoplastic left heart syndrome, there was
      no difference in post-operative haemodynamics between two groups, but the total
      amount of chest drainage after total cavopulmonary connection was larger in the
      younger group (109+/-95 versus 55+/-40 ml/kg; p=0.044). CONCLUSIONS: Early
      bidirectional cavopulmonary anastomosis did not affect the outcome of total
      cavopulmonary connection. Longer chest tube period, smaller pulmonary artery, and
      higher pulmonary artery pressure after total cavopulmonary connection were
      recognised in early bidirectional cavopulmonary anastomosis patients, especially
      in hypoplastic left heart syndrome.

PMID- 30198457
TI  - Dysphagia characteristics in Huntington's disease patients: insights from the
      Fiberoptic Endoscopic Evaluation of Swallowing and the Swallowing Disturbances
      Questionnaire.
AB  - BACKGROUND: Huntington's disease (HD) is a neurodegenerative disease
      characterized by increasing dysphagia as the disease progresses. Specific
      characteristics of the HD dysphagia are not well defined. OBJECTIVE: To
      characterize the swallowing disturbances of HD patients, to evaluate the
      feasibility of Fiberoptic Endoscopic Evaluation of Swallowing (FEES) in assessing
      dysphagia in HD patients, and to discern the relation between FEES findings and
      patients' self-report on dysphagia symptoms and swallowing related quality of
      life (SWAL-QOL). METHOD: A retrospective case series in a tertiary referral
      center. All recruited HD patients underwent Bed Side Swallowing Evaluation (BSE),
      FEES, the Unified Huntington's Disease Rating Scale (UHDRS), and the Montreal
      Cognitive Assessment (MoCA). All completed the Swallowing Disturbances
      Questionnaire (SDQ) and the SWAL-QOL questionnaire. RESULTS: Fourteen HD patients
      were recruited. All were able to complete the FEES study. The FEES demonstrated
      delayed swallowing reflex, solid food residues, and pre/post swallowing spillage
      in most patients (50%, 53.5%, 83.3%, and 87.5%, respectively). The mean SDQ score
      was 13.2. Significant correlations were found between the SWAL-QOL fear of eating
      score; the SDQ oral, pharyngeal, and total scores; and the FEES parameters of
      pureed and solid food bolus flow time. Significant correlations were also found
      between the total UHDRS score, the volitional cough score, and the SWAL-QOL
      disease burden score. CONCLUSION: HD patients exhibit prominent unique
      oropharyngeal dysphagia features that may serve as a marker of disease
      progression. The FEES and the SDQ are valuable tools for detecting these features
      in HD patients with swallowing disturbance.

PMID- 30198458
TI  - Artificial sweeteners in food and beverage products at school.
AB  - OBJECTIVE: Experts recommend that products containing artificial sweeteners are
      not marketed to children or sold at schools. The present study aimed to provide a
      baseline assessment of the extent to which state laws and local school district
      wellness policies (LWP) address restrictions on the use of artificial sweeteners
      in competitive foods and beverages (CF&B) sold at schools. DESIGN: A descriptive,
      cross-sectional study of policies in place for the 2014-15 school year. SETTING:
      Data were collected on laws in all fifty states and Washington, DC. LWP were
      compiled for 496/518 school food authorities (SFA) for which data were collected
      as part of the US Department of Agriculture's School Nutrition and Meal Cost
      Study. SUBJECTS: State laws and LWP respectively were coded on a 0-3 ordinal
      scale for the strength of their restrictions on artificial sweeteners in CF&B
      sold in each of five CF&B venues, separately by grade level. Prevalence of state
      laws and LWP for SFA nationwide was computed. RESULTS: Thirteen states addressed
      the use of artificial sweeteners. Six states addressed the use of artificial
      sweeteners in both CF&B. District-level artificial sweetener policies were most
      frequently addressed for beverages in elementary schools' vending machines.
      District policies also were more likely to address artificial sweeteners in
      states with laws addressing artificial sweeteners. CONCLUSIONS: Most state laws
      and LWP do not address artificial sweeteners in CF&B. This is not surprising
      given the Food and Drug Administration has approved eight artificial sweeteners
      for consumption and the Smart Snacks regulation does not limit artificial
      sweeteners for CF&B.

PMID- 30198459
TI  - High-through identification of T cell-specific phage-exposed mimotopes using
      PBMCs from tegumentary leishmaniasis patients and their use as vaccine candidates
      against Leishmania amazonensis infection.
AB  - In the current study, phage-exposed mimotopes as targets against tegumentary
      leishmaniasis (TL) were selected by means of bio-panning cycles employing sera of
      TL patients and healthy subjects, besides the immune stimulation of peripheral
      blood mononuclear cells (PBMCs) collected from untreated and treated TL patients
      and healthy subjects. The clones were evaluated regarding their specific
      interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) production in the in vitro
      cultures, and selectivity and specificity values were calculated, and those
      presenting the best results were selected for the in vivo experiments. Two
      clones, namely A4 and A8, were identified and used in immunization protocols from
      BALB/c mice to protect against Leishmania amazonensis infection. Results showed a
      polarized Th1 response generated after vaccination, being based on significantly
      higher levels of IFN-gamma, IL-2, IL-12, tumour necrosis factor-alpha (TNF-alpha)
      and granulocyte-macrophage colony-stimulating factor (GM-CSF); which were
      associated with lower production of specific IL-4, IL-10 and immunoglobulin G1
      (IgG1) antibodies. Vaccinated mice presented significant reductions in the
      parasite load in the infected tissue and distinct organs, when compared with
      controls. In conclusion, we presented a strategy to identify new mimotopes able
      to induce Th1 response in PBMCs from TL patients and healthy subjects, and that
      were successfully used to protect against L. amazonensis infection.

PMID- 30198460
TI  - Stapedotomy using a 4 mm endoscope: any advantage over a microscope?
AB  - OBJECTIVES: To ascertain the feasibility of endoscopic (4 mm) stapedotomy, and
      compare intra- and post-operative variations with microscopic stapedotomies.
      METHODS: Forty otosclerosis patients were scheduled for microscopic or endoscopic
      stapedotomy. Intra-operative variables compared were: incision, canalplasty,
      canal wall curettage for ossicular assessment, chorda tympani manipulation,
      ability to perform stapes footplate perforation before its supra-structure
      removal, and operative time. Post-operative variables compared were ear pain and
      hearing improvement. RESULTS: Of the 20 microscopy patients, 4 required endaural
      incision and canalplasty because of canal overhangs, and 7 required canal wall
      curettage for ossicular assessment. None of the 20 endoscopy patients required
      these procedures. Chorda tympani was manipulated in 13 and 6 patients in the
      microscopy and endoscopy groups respectively, while the stapes footplate could be
      perforated in 5 and 11 patients respectively. Mean operative time was 50.25 and
      76.05 minutes in the microscopy and endoscopy groups respectively. In the
      endoscopy group, mean air-bone gap was 37.12 and 10.73 dB pre- and post-operation
      respectively; in the microscopy group, these values were 35.95 and 13.81 dB.
      CONCLUSION: Endoscopic stapedotomy has comparable hearing outcomes. Sinonasal
      endoscope serves as a better tool for: minimal incision, canalplasty avoidance,
      less chorda tympani mobilisation, and stapes footplate perforation ability.

PMID- 30198463
TI  - Constructive Disappointment and Disbelief: Building a Career in Neuroethics.
AB  - Sometimes one's greatest academic disappointments can have unexpected outcomes.
      This is especially true when one is trying to change career trajectories or do
      something that others did not take seriously. My path into neuroethics was an
      unexpected journey catalyzed in part by constructive disappointment and the
      disbelief of colleagues who thought that the work I was pursuing nearly two
      decades prior was a fool's errand. After all, could anyone-in his or her right
      mind-ever conceive of waking up a person unconscious from brain injury and
      getting him to speak? 1.

PMID- 30198461
TI  - Audiologist-led screening of acoustic neuromas in patients with asymmetrical
      sensorineural hearing loss and/or unilateral tinnitus: our experience in 1126
      patients.
AB  - OBJECTIVE: To determine whether patients within an otolaryngology department
      presenting with asymmetrical sensorineural hearing loss and/or unilateral
      tinnitus can be safely and cost-efficiently screened for acoustic neuroma by
      audiologists as a first or only point of contact. METHODS: A prospective case
      series and cost analysis were conducted at a tertiary referral centre. Between
      April 2013 and March 2017, 1126 adult patients presented to the audiology
      department with asymmetrical sensorineural hearing loss and/or unilateral
      tinnitus. All were screened for acoustic neuroma with magnetic resonance imaging,
      based on pre-determined criteria. The main outcome measure was the presence of
      acoustic neuroma or other pathology on magnetic resonance imaging. RESULTS:
      Twenty-five patients (2.22 per cent) were found to have an acoustic neuroma (size
      range: 3-20 mm) and were referred to the otolaryngologist for further assessment.
      The remaining patients were appropriately managed and discharged by the
      audiologists without ENT input. This resulted in an overall cost saving of L164
      850. CONCLUSION: Patients with asymmetrical sensorineural hearing loss and/or
      unilateral tinnitus can be safely screened for acoustic neuroma and independently
      managed by audiologists as a first or only point of contact, resulting in
      considerable departmental cost savings.

PMID- 30198462
TI  - Timing of palliative care access and outcomes of advanced cancer patients
      referred to an inpatient palliative care consultation team in Brazil.
AB  - OBJECTIVE: Little is known about the outcomes of cancer patients referred to
      palliative care (PC) teams in developing countries. Our aim was to examine the
      timing of PC access and outcomes of patients with advanced cancer referred to an
      inpatient PC consultation team in Brazil. METHOD: Retrospective study of
      consecutive patients with advanced cancer admitted to a tertiary care general
      hospital (April 2015-December 2016) and referred for the first time to an
      inpatient PC consultation team. Patients' demographics, clinical features, time
      from first consult to death or discharge, and outcomes on medication use,
      clinical interventions, and end-of-life preferences were retrieved. An analysis
      was performed before and after PC.ResultOne hundred eleven patients were
      included. Median age was 68; 72% had an Eastern Cooperative Oncology Group
      performance status >=3. The median timing of PC access was 9 days (first
      interquartile = 3, third interquartile = 19). The use of analgesics (from 75% to
      85%, p = 0.001) and opioids (from 50% to 73%, p < .001) increased. A lower
      proportion was receiving antibiotics (68% vs 48%, p < 0.001), thromboprophylaxis
      (44% vs 26%, p < 0.001), antihypertensives (28% vs 15%, p = 0.001), and
      antiemetic agents (64% vs 54%, p = 0.027). Chemotherapy use was lower (39-25%, p
      < 0.001). More patients had an end-of-life preference (39% to 25%, p < 0.001) and
      were not willing to receive intubation (32% vs 60%, p < 0.001), intensive care
      treatment (30% vs 55%, p < 0.001), cardiopulmonary resuscitation (35% vs 62%, p <
      0.001), and artificial nutrition (22% vs 34%, p < 0.001).Significance of
      resultsAlthough PC referrals occurred exceedingly late during the cancer disease
      trajectory, positive changes were observed in medication profiles, clinical
      interventions use, and end-of-life preferences of patients with advanced cancer
      referred to a specialized inpatient PC consultation team in Brazil. Further
      efforts are needed to improve early palliative cancer care in developing
      countries.

PMID- 30198464
TI  - If It Only Had a Brain: What "Neuro" Means for Science and Ethics.

PMID- 30198465
TI  - Neurophilosophical and Ethical Aspects of Virtual Reality Therapy in Neurology
      and Psychiatry.
AB  - Highly immersive virtual reality (VR) systems have been introduced into the
      consumer market in recent years. The improved technological capabilities of these
      systems as well as the combination with biometric sensors, for example
      electroencephalography (EEG), in a closed-loop hybrid VR-EEG, opens up a range of
      new potential medical applications. This article first provides an overview of
      the past and current clinical applications of VR systems in neurology and
      psychiatry and introduces core concepts in neurophilosophy and VR research (such
      as agency, trust, presence, and others). Then, important adverse effects of
      highly immersive VR simulations and the ethical implications of standalone and
      hybrid VR systems for therapy in neurology and psychiatry are highlighted. These
      new forms of VR-based therapy may strengthen patients in exercising their
      autonomy. At the same time, however, these emerging systems present ethical
      challenges, for example in terms of moral and legal accountability in
      interactions involving "intelligent" hybrid VR systems. A user-centered approach
      that is informed by the target patients' needs and capabilities could help to
      build beneficial systems for VR therapy.

PMID- 30198466
TI  - Brain-Computer Interfaces: Lessons to Be Learned from the Ethics of Algorithms.
AB  - Brain-computer interfaces (BCIs) are driven essentially by algorithms; however,
      the ethical role of such algorithms has so far been neglected in the ethical
      assessment of BCIs. The goal of this article is therefore twofold: First, it aims
      to offer insights into whether (and how) the problems related to the ethics of
      BCIs (e.g., responsibility) can be better grasped with the help of already
      existing work on the ethics of algorithms. As a second goal, the article explores
      what kinds of solutions are available in that body of scholarship, and how these
      solutions relate to some of the ethical questions around BCIs. In short, the
      article asks what lessons can be learned about the ethics of BCIs from looking at
      the ethics of algorithms. To achieve these goals, the article proceeds as
      follows. First, a brief introduction into the algorithmic background of BCIs is
      given. Second, the debate about epistemic concerns and the ethics of algorithms
      is sketched. Finally, this debate is transferred to the ethics of BCIs.

PMID- 30198467
TI  - Ethical Considerations in Ending Exploratory Brain-Computer Interface Research
      Studies in Locked-in Syndrome.
AB  - Brain-computer interface (BCI) is a promising technology for restoring
      communication in individuals with locked-in syndrome (LIS). BCI technology offers
      a potential tool for individuals with impaired or absent means of effective
      communication to use brain activity to control an output device such as a
      computer keyboard. Exploratory studies of BCI devices for communication in people
      with LIS are underway. Research with individuals with LIS presents not only
      technological challenges, but ethical challenges as well. Whereas recent
      attention has been focused on ethical issues that arise at the initiation of
      studies, such as how to obtain valid consent, relatively little attention has
      been given to issues at the conclusion of studies. BCI research in LIS highlights
      one such challenge: How to decide when an exploratory BCI research study should
      end. In this article, we present the case of an individual with presumed LIS
      enrolled in an exploratory BCI study. We consider whether two common ethical
      frameworks for stopping randomized clinical trials-equipoise and nonexploitation
      can be usefully applied to elucidating researcher obligations to end exploratory
      BCI research. We argue that neither framework is a good fit for exploratory BCI
      research. Instead, we apply recent work on clinician-researcher fiduciary
      obligations and in turn offer some preliminary recommendations for BCI
      researchers on how to end exploratory BCI studies.

PMID- 30198468
TI  - Amplio, Ergo Sum.
AB  - This article aims to explore the idea that enhancement technologies have been and
      will continue to be an essential element of what we might call the "human
      continuum," and are indeed key to our existence and evolution into persons.
      Whereas conservative commentators argue that enhancement is likely to cause us to
      lose our humanity and become something other, it is argued here that the very
      opposite is true: that enhancement is the core of what and who we are. Using
      evidence from paleoanthropology to examine the nature of our predecessor species,
      and their proclivities for tool use, we can see that there is good reason to
      assume that the development of Homo sapiens is a direct result of the use of
      enhancement technologies. A case is also made for broad understandings of the
      scope of enhancement, based on the significant evolutionary results of acts that
      are usually dismissed as "unremarkable." Furthermore, the use of enhancement by
      modern humans is no different than these prehistoric applications, and is likely
      to ultimately have similar results. There is no good reason to assume that
      whatever we may become will not also consider itself human.

PMID- 30198469
TI  - Call of Duty at the Frontier of Research: Normative Epistemology for High
      Risk/High-Gain Studies of Deep Brain Stimulation.
AB  - Research participants are entitled to many rights that may easily come into
      conflict. The most important ones are that researchers respect their autonomy as
      persons and act on the principles of beneficence, nonmaleficence, and justice.
      Since 2014, research subjects from numerous states in the United States of
      America also have a legal "right to try" that allows them, under certain
      circumstances, to receive experimental (i.e., preliminarily tested)
      interventions, including medical devices, before official approval from the
      United States Food and Drug Administration. In the context of experimental
      interventions, such as deep brain stimulation (DBS) for Alzheimer's disease, this
      article argues that research participants ought never to have a legal "right to
      try" without a corresponding "right to be sure." The latter refers to external
      epistemic justification construed in terms of reliance on reliable evidence. This
      article demonstrates that the mere complexity of intervention ensembles, as in
      the case of DBS for Alzheimer's disease which serves as a paradigm example,
      illustrate how unanswered and/or unasked open questions give rise to a
      "combinatorial explosion" of uncertainties that require epistemic responses that
      no single research team alone is likely able to provide. From this assessment,
      several epistemic asymmetrical relations between researchers and participants are
      developed. By elucidating these epistemic asymmetries, this article unravels the
      reasons why open science, transparent exhaustive data reporting, preregistration,
      and continued constant critical appraisal via pre- and postpublication peer
      review are not scientific virtues of moral excellence but rather ordinary
      obligations of the scientific work routine required to increase reliability and
      strength of evidence.

PMID- 30198471
TI  - Doing Good, Choosing Freely: How Moral Enhancement Can Be Compatible with
      Individual Freedom.
AB  - Moral enhancement has been accused of curtailing human freedoms. In this article,
      I suggest the opposite: moral enhancement and individual freedom can go hand in
      hand. The first section defines freedom, enhancement, and morality and argues
      that only a naturalistic account of morality allows for the concept of
      enhancement. The second section looks at ways that freedom may be threatened by
      moral enhancement, especially by the method of implementation, the creation of
      new externalities, or the limitation of volitional options. I argue that virtue
      ethics offers the safest model for moral enhancement. The third section describes
      ways in which moral enhancement can be achieved while maintaining, or even
      increasing, individual freedom. Such methods include shifting of the moral axis,
      replacing vicious options with virtuous ones, and increasing the number of
      volitional options available. The article concludes in the fourth section by
      arguing that the technology and techniques that allow us moral enhancement are
      likely to be the same ones that allow greater freedom than we already enjoy.

PMID- 30198470
TI  - Do New Neuroimaging Findings Challenge the Ethical Basis of Advance Directives in
      Disorders of Consciousness?
AB  - Some authors have questioned the moral authority of advance directives (ADs) in
      cases in which it is not clear if the author of the AD is identical to the person
      to whom it later applies. This article focuses on the question of whether the
      latest results of neuroimaging studies have moral significance with regard to the
      moral authority of ADs in patients with disorders of consciousness (DOCs). Some
      neuroimaging findings could provide novel insights into the question of whether
      patients with DOCs exhibit sufficient psychological continuity to be ascribed
      diachronic personal identity. If those studies were to indicate that
      psychological continuity is present, they could justify the moral authority of
      ADs in patients with DOCs. This holds at least if respect for self-determination
      is considered as the foundation for the moral authority of ADs. The non-identity
      thesis in DOCs could no longer be applied, in line with clinical and social
      practice.

PMID- 30198473
TI  - Commentary: Doing the Most Good with the Least Harm in Cases of Suspected
      Malingering.

PMID- 30198472
TI  - Neuroethics: A Conceptual Approach.
AB  - In this article, we begin by identifying three main neuroethical approaches:
      neurobioethics, empirical neuroethics, and conceptual neuroethics. Our focus is
      on conceptual approaches that generally emphasize the need to develop and use a
      methodological modus operandi for effectively linking scientific (i.e.,
      neuroscience) and philosophical (i.e., ethics) interpretations. We explain and
      assess the value of conceptual neuroethics approaches and explain and defend one
      such approach that we propose as being particularly fruitful for addressing the
      various issues raised by neuroscience: fundamental neuroethics.

PMID- 30198474
TI  - Concussion in Sport: The Unheeded Evidence.
AB  - Patients with repeated minor head injury are a challenge to our clinical skills
      of neurodiagnosis because the relevant evidence objectively demonstrating their
      impairment was collected in New Zealand (although published in the BMJ and
      Lancet) and, at the time, was mired in controversy. The effects of repeated
      closed diffuse head injury are increasingly recognized worldwide, but now suffer
      from the relentless advance of imaging technology as the dominant form of
      neurodiagnosis and the considerable financial interests that underpin the refusal
      to recognize that acute accelerational injury is the most subtle and insidiously
      damaging (especially when seen in the light of biopsychosocial medicine), and
      potentially one of the most financially momentous (given the large incomes
      impacted and needing compensation) phenomena in modern sports medicine. The
      vested interests in downplaying this phenomenon are considerable and concentrated
      in North America where diffuse head injury is a widespread feature of the
      dominant winter sports code: Gridiron or American Rules football. The
      relationship of this to shattered lives among the brightest and best of young men
      and the relatively dated objective evidence are a toxic mix in terms of ethical
      analysis and, therefore, there is a malignant confluence of social forces that
      tends toward minimizing the injury.

PMID- 30198475
TI  - Looking Ahead: The Importance of Views, Values, and Voices in Neuroethics-Now.
AB  - The body-to-head transplant (BHT) planned to be undertaken later this year at
      China's Harbin Medical University by neurosurgeons Sergio Canavero and Xiaoping
      Ren has attracted considerable attention and criticism. The intended operation
      gives rise to philosophical queries about the body-brain-mind relationship and
      nature of the subjective self; technical and ethical issues regarding the
      scientific soundness, safety, and futility of the procedure; the adequacy of
      prior research; and the relative merit, folly, and/or danger of forging new
      boundaries of what is biomedically possible. Moreover, that this procedure, which
      has been prohibited from being undertaken in other countries, has been sanctioned
      in China brings into stark relief ways that differing social and political
      values, philosophies, ethics, and laws can affect the scope and conduct of
      research. Irrespective of whether the BHT actually occurs, the debate it has
      generated reveals and reflects both the evermore international enterprise of
      brain science, and the need for neuroethical discourse to include and appreciate
      multicultural views, values, and voices.

PMID- 30198477
TI  - Commentary: Treating the Patient Who Has the Disease.

PMID- 30198476
TI  - The Case: Medically Disabled or Malingering?

PMID- 30198478
TI  - Neuroscience and Social Problems: The Case of Neuropunishment.
AB  - Neuroscientific interventions are increasingly proposed as solutions for social
      problems, beyond their application in biomedicine. For example, there is
      increasing interest, particularly from outside commentators, in harnessing
      neuroscientific advances as an alternative method of punishing criminal
      offenders. Such neuropunishments are seen as a potentially more effective, less
      costly, and more humane alternative to incarceration, with overall better results
      for offender, communities, and societies. This article considers whether
      neuroscience as a field should engage more actively with such proposals, and
      whether more research should be done to explore the use of neurointerventions for
      punishment. It concludes that neuroscientists and those working at the
      intersection of neuroscience and the clinic should actively shape these debates.

PMID- 30198479
TI  - Neuronal underpinnings of cognitive impairment and - improvement in mood
      disorders.
AB  - Neuropsychiatric illnesses including mood disorders are accompanied by cognitive
      impairment, which impairs work capacity and quality of life. However, there is a
      lack of treatment options that would lead to solid and lasting improvement of
      cognition. This is partially due to the absence of valid and reliable
      neurocircuitry-based biomarkers for pro-cognitive effects. This systematic review
      therefore examined the most consistent neural underpinnings of cognitive
      impairment and cognitive improvement in unipolar and bipolar disorders. We
      identified 100 studies of the neuronal underpinnings of working memory and
      executive skills, learning and memory, attention, and implicit learning and 9
      studies of the neuronal basis for cognitive improvements. Impairments across
      several cognitive domains were consistently accompanied by abnormal activity in
      dorsal prefrontal (PFC) cognitive control regions-with the direction of this
      activity depending on patients' performance levels-and failure to suppress
      default mode network (DMN) activity. Candidate cognition treatments seemed to
      enhance task-related dorsal PFC and temporo-parietal activity when performance
      increases were observed, and to reduce their activity when performance levels
      were unchanged. These treatments also attenuated DMN hyper-activity. In contrast,
      nonspecific cognitive improvement following symptom reduction was typically
      accompanied by decreased limbic reactivity and reversal of pre-treatment fronto
      parietal hyper-activity. Together, the findings highlight some common neural
      correlates of cognitive impairments and cognitive improvements. Based on this
      evidence, studies are warranted to examine the reliability and predictive
      validity of target engagement in the identified neurocircuitries as a biomarker
      model of pro-cognitive effects.

PMID- 30198480
TI  - High national and sub-national coverage of iodised salt in India: evidence from
      the first National Iodine and Salt Intake Survey (NISI) 2014-2015.
AB  - OBJECTIVE: The National Iodine and Salt Intake Survey (NISI) 2014-2015 was
      undertaken to estimate household iodised salt coverage at national and sub
      national levels in India. DESIGN: Cross-sectional survey with multistage
      stratified random sampling. SETTING: India was divided into six geographic zones
      (South, West, Central, North, East and North-East) and each zone was further
      stratified into rural and urban areas to yield twelve distinct survey strata.
      SUBJECTS: The target respondent from each household was selected as per
      predefined priority; wife of the household head, followed by women of
      reproductive age, followed by any adult available during the visit. RESULTS:
      Households (n 5717) were surveyed and salt samples (n 5682) were analysed.
      Household coverage of iodised salt (iodine>=5 ppm) was 91.7 (95 % CI 91.0, 92.7)
      %. Adequately iodised salt (iodine>=15 ppm) was consumed in 77.5 (95 % CI 76.4,
      78.6) % of households. Significant differences in coverage were seen across six
      geographic regions, with North and North-East zones on the verge of achieving the
      universal salt iodisation target of >90 % coverage. Coverage of households with
      adequately iodised salt (adjusted OR; 95 % CI) was significantly less in rural
      households (0.55; 0.47, 0.64), lower/backward castes (0.84; 0.72, 0.98), deprived
      households (0.72; 0.61, 0.85) as assessed by multidimensional poverty index,
      households with non-diverse diet (0.73; 0.62, 0.86) and households using non
      packaged salt (0.48; 0.39, 0.59) and non-refined salt (0.17; 0.15, 0.20).
      CONCLUSIONS: India is within striking reach of achieving universal salt
      iodisation. However, significant differentials by rural/urban, zonal and socio
      economic indicators exist, warranting accelerated efforts and targeted
      interventions for high-risk groups.

PMID- 30198483
TI  - Correction to Lancet Child Adolesc Health 2017; 1: 97-105.

PMID- 30198484
TI  - Disentangling causes of seasonal infection prevalence patterns: tropical tadpoles
      and chytridiomycosis as a model system.
AB  - Identifying the factors that affect pathogen prevalence is critical to
      understanding the effects of wildlife diseases. We aimed to examine drivers of
      seasonal changes in the prevalence of infection by the amphibian chytrid fungus
      Batrachochytrium dendrobatidis in tadpoles. Because tadpoles may be important
      reservoirs for this disease, examining them will aid in understanding how
      chytridiomycosis affects entire amphibian populations. We hypothesized that
      temperature is a strong driver of prevalence of Bd in tadpoles, and the
      accumulation of infection as tadpoles become larger and older also drives
      prevalence in this system. We studied Litoria rheocola, a tropical rainforest
      stream frog with seasonal recruitment of annual tadpoles, and surveyed 6 streams
      in northeastern Queensland, Australia. Comparisons among models relating
      infection status to stream type, season, their interaction, tadpole age, and
      water temperature showed that age explained a large portion of the variance in
      infection status. Across sites and seasons, larger, older tadpoles had increased
      mean probabilities of infection, indicating that a large component of the
      variation among individuals was related to age, and thus to cumulative infection
      risk. Our results indicate that in systems with annual tadpoles, seasonal changes
      in infection prevalence may be strongly affected by seasonal patterns of tadpole
      growth and development in addition to stream type, season, and water temperature.
      These effects may then influence prevalence of infection in terrestrial
      individuals in species that have relatively frequent contact with water. This
      reinforces the need to integrate studies of the drivers of pathogen prevalence
      across all host life history stages.

PMID- 30198485
TI  - Isolation, characterization and molecular identification of a novel aquareovirus
      that infects endangered fountain darter Etheostoma fonticola.
AB  - The fountain darter Etheostoma fonticola (FOD) is a federally endangered fish
      listed under the US Endangered Species Act. Here, we identified and characterized
      a novel aquareovirus isolated from wild fountain darters inhabiting the San
      Marcos River. This virus was propagated in Chinook salmon embryo (CHSE)-214,
      rainbow trout gonad-2 and fathead minnow cells at 15 degrees C. The epithelioma
      papulosum cyprini cell line was refractory at all temperatures evaluated. High
      throughput sequencing technologies facilitated the complete genome sequencing of
      this virus utilizing ribosomal RNA-depleted RNA extracted from infected CHSE-214
      cells. Conventional PCR primer sets were developed for the detection and
      confirmation of this virus to assist diagnostic screening methods. Phylogenetic
      analysis suggests this virus belongs to the Aquareovirus A genus. This research
      provides requisite initial data critical to support hatchery and refugia
      biosecurity measures for this endangered species.

PMID- 30198482
TI  - Intermittent subthalamic nucleus deep brain stimulation induces risk-aversive
      behavior in human subjects.
AB  - The subthalamic nucleus (STN) is a small almond-shaped subcortical structure
      classically known for its role in motor inhibition through the indirect pathway
      within the basal ganglia. Little is known about the role of the STN in mediating
      cognitive functions in humans. Here, we explore the role of the STN in human
      subjects making decisions under conditions of uncertainty using single-neuron
      recordings and intermittent deep brain stimulation (DBS) during a financial
      decision-making task. Intraoperative single-neuronal data from the STN reveals
      that on high-uncertainty trials, spiking activity encodes the upcoming decision
      within a brief (500 ms) temporal window during the choice period, prior to the
      manifestation of the choice. Application of intermittent DBS selectively prior to
      the choice period alters decisions and biases subject behavior towards
      conservative wagers.

PMID- 30198481
TI  - Structural principles of SNARE complex recognition by the AAA+ protein NSF.
AB  - The recycling of SNARE proteins following complex formation and membrane fusion
      is an essential process in eukaryotic trafficking. A highly conserved AAA+
      protein, NSF (N-ethylmaleimide sensitive factor) and an adaptor protein, SNAP
      (soluble NSF attachment protein), disassemble the SNARE complex. We report
      electron-cryomicroscopy structures of the complex of NSF, alphaSNAP, and the full
      length soluble neuronal SNARE complex (composed of syntaxin-1A, synaptobrevin-2,
      SNAP-25A) in the presence of ATP under non-hydrolyzing conditions at ~3.9 A
      resolution. These structures reveal electrostatic interactions by which two
      alphaSNAP molecules interface with a specific surface of the SNARE complex. This
      interaction positions the SNAREs such that the 15 N-terminal residues of SNAP-25A
      are loaded into the D1 ring pore of NSF via a spiral pattern of interactions
      between a conserved tyrosine NSF residue and SNAP-25A backbone atoms. This
      loading process likely precedes ATP hydrolysis. Subsequent ATP hydrolysis then
      drives complete disassembly.

PMID- 30198486
TI  - Red seabream iridovirus associated with cultured Florida pompano Trachinotus
      carolinus mortality in Central America.
AB  - Mariculture of Florida pompano Trachinotus carolinus in Central America has
      increased over the last few decades and it is now a highly valued food fish. High
      feed costs and infectious diseases are significant impediments to the expansion
      of mariculture. Members of the genus Megalocytivirus (MCV), subfamily
      Alphairidovirinae, within the family Iridoviridae, are emerging pathogens that
      negatively impact Asian mariculture. A significant mortality event in Florida
      pompano fingerlings cultured in Central America occurred in October 2014.
      Affected fish presented with abdominal distension, darkening of the skin, and
      periocular hemorrhages. Microscopic lesions included cytomegalic 'inclusion body
      bearing cells' characterized by basophilic granular cytoplasmic inclusions in
      multiple organs. Transmission electron microscopy revealed arrays of hexagonal
      virions (155-180 nm in diameter) with electron-dense cores within the cytoplasm
      of cytomegalic cells. Pathological findings were suggestive of an MCV infection,
      and the diagnosis was later confirmed by partial PCR amplification and sequencing
      of the viral gene encoding the myristylated membrane protein. The viral sequence
      revealed that the fingerlings were infected with an MCV genotype, red seabream
      iridovirus (RSIV), previously reported only from epizootics in Asian mariculture.
      This case underscores the threat RSIV poses to global mariculture, including the
      production of Florida pompano in Central America.

PMID- 30198488
TI  - Effect of tidal level on abundance of symbionts in the White Sea blue mussel.
AB  - In the White Sea, the blue mussel Mytilus edulis occupies a wide range of
      biotopes and is associated with numerous symbiotic organisms. At some sites,
      mussel cover spreads continuously from the intertidal to the subtidal zone. We
      checked whether the patterns of infection by different associated organisms
      differed among the upper subtidal, zero-depth and lower intertidal zones at 3
      sites in the Kandalaksha Gulf and the Onega Bay of the White Sea. Organisms
      belonging to 13 taxa were found in mantle cavities and tissues of blue mussels.
      Parasitic green algae, a sporocyst and metacercariae of 5 species of digenean
      trematodes occupied mussel tissues; commensal ciliates, rhabdocoelans and some
      free-living invertebrates were found in mantle cavities. Quantitative composition
      of symbiotic communities of mussels was not the same at different tidal levels:
      Urastoma cyprinae (commensal rhabdocoelans) were more abundant in the subtidal
      and zero-depth zones, while encysted metacercariae of Renicola roscovita and
      Himasthla sp. were more abundant at the zero-depth and intertidal zones. We
      suggested several hypotheses to explain this heterogeneity.

PMID- 30198487
TI  - Edwardsiella ictaluri type III secretion system (T3SS) effector EseN is a
      phosphothreonine lyase that inactivates ERK1/2.
AB  - EseN is a type III secretion system (T3SS) effector that is encoded on the
      Edwardsiella ictaluri chromosome and is homologous to a family of T3SS effector
      proteins with phosphothreonine lyase (PTL) activity, including OspF from Shigella
      and SpvC from Salmonella. A yeast-2-hybrid system was used to identify the major
      vault protein (MVP) as a specific host-cell binding partner for EseN, and the
      proximity ligation assay (PLA) confirmed the interaction. Similar to other
      pathogens, E. ictaluri invasion activates extracellular signal-regulated kinases
      1 and 2 (ERK1/2) early in the infection, which are subsequently inactivated by
      EseN. Structurally, EseN contains a highly conserved docking motif that is
      required for specific binding to mitogen-activated protein kinases, such as
      ERK1/2, and a motif that is essential for PTL activity. Immunoblotting and
      immunofluorescence analyses indicate that EseN inactivates ERK1/2 by
      dephosphorylation in vivo in the head kidney of infected fish and ex vivo in head
      kidney derived macrophages. Interaction of EseN with phosphorylated ERK1/2
      (pERK1/2) was also confirmed using PLA, suggesting that MVP serves as a signaling
      scaffold for ERK1/2 and EseN. Channel catfish Ictalurus punctatus infected with
      E. ictaluri strains lacking the eseN gene had reduced numbers of E. ictaluri in
      the tissues following infection and reduced mortality compared to fish infected
      with the wild-type. Our results indicate that eseN encodes a PTL domain that
      interacts with MVP as a possible scaffold protein and inactivates pERK1/2 to
      ERK1/2, resulting in increased proliferation of E. ictaluri and, ultimately,
      death of the host.

PMID- 30198489
TI  - Internal parasites of the two subspecies of the West Indian manatee Trichechus
      manatus.
AB  - The West Indian manatee Trichechus manatus is divided into 2 subspecies: the
      Antillean (T. m. manatus) and Florida (T. m. latirostris) manatees. This study
      reports sample prevalence of manatee parasites from populations of these 2
      subspecies in different geographical locations. Although necropsy is a valuable
      diagnostic tool for parasite infections, the need for antemortem diagnostic
      techniques is important. Fecal samples collected during necropsies of Antillean
      manatees (n = 3) in Puerto Rico and Florida manatees (n = 10) in Crystal River,
      Florida, as well as from live-captured Florida manatees (n = 11) were evaluated
      using centrifugal flotation with sucrose and ethyl acetate sedimentation to
      compare parasites from each of the populations. Although both fecal examination
      methods provided similar results, the centrifugal flotation method required less
      time for diagnosis. The most common parasite eggs found in both populations
      included the trematodes Pulmonicola cochleotrema and Nudacotyle undicola, oocysts
      of the coccidian Eimeria spp., and eggs of the ascarid Heterocheilus tunicatus.
      Eggs of the trematode Chiorchis groschafti were found in both populations of
      manatees; however, eggs of a related species, Chiorchis fabaceus, were abundant
      in the Florida samples, but not found in Puerto Rico populations. Trematode eggs
      of Moniligerum blairi were found in both populations, but were more common in the
      Florida manatee (42%) than the Antillean manatee (33%). To our knowledge, this is
      the first report of both Eimeria manatus and Eimeria nodulosa oocysts in
      Antillean manatees from Puerto Rico.

PMID- 30198490
TI  - Pyogranulomatous obliterative laryngotracheitis by Rhizopus arrhizus (syn. R.
      oryzae) in a free-ranging Atlantic spotted dolphin Stenella frontalis.
AB  - We report the gross and microscopic findings and molecular identification of
      fungal hyphate infection in a juvenile female Atlantic spotted dolphin Stenella
      frontalis found dead off Arguineguin, Gran Canaria (Canary Islands, Spain). On
      necropsy examination, the animal had a large cranial intrathoracic mass and
      multiple variably-sized nodules throughout the larynx and trachea that
      obliterated the lumen. Microscopically, the masses were composed of abundant
      pyogranulomatous inflammation with numerous fungal hyphae. These were
      pauciseptate (coenocytic) and had non-parallel walls, non-dichotomous irregular
      to right angle branching, and bulbous dilations. PCR analysis from these
      inflammatory foci yielded Rhizopus arrhizus (syn. R. oryzae). This fungal
      pathogen is often ascribed to opportunistic infections in immunosuppressed humans
      and animals. In the present case, a potential cause for immunosuppression was not
      identified; PCR analysis for cetacean morbillivirus was negative. Herein, we
      report the first confirmed case of R. arrhizus infection in a free-living
      Atlantic cetacean. These findings add to the body of knowledge on fungal disease
      in cetaceans in general and, in particular, in odontocetes, where respiratory
      involvement is common.

PMID- 30198491
TI  - Larval digenean communities in Biomphalaria species in two contrasting wetlands
      from South America.
AB  - A key factor in the colonization probabilities of parasites is the host's
      characteristic habitat. Considering that rice fields are simple habitats compared
      with natural wetlands, we comparatively analyzed the composition of the cercariae
      communities in Biomphalaria snails in an agricultural and a nonagricultural
      habitat of Corrientes Province, Argentina. We collected 2998 Biomphalaria snails
      from November 2011 to May 2012: B. tenagophila, B. occidentalis, B. peregrina,
      and B. orbignyi in the nonagricultural habitat and B. straminea in the
      agricultural habitat. Nine cercaria species were found in the nonagricultural
      habitat and 12 in the agricultural habitat, with overall parasite prevalence of
      9.27 and 7.69%, respectively. The overall prevalence and mean species richness of
      cercariae showed no significant differences between habitats. The cercariae
      communities of the 2 habitats showed low similarity (38%), sharing 4 species. The
      mean species diversity of cercariae was higher in the nonagricultural habitat.
      Our results suggest that rice fields provide conditions for the hosts and
      cercariae that are somewhat similar to those of nonagricultural wetlands,
      although the contrasting characteristics of habitats can influence the presence
      of different intermediate and definitive hosts and consequently impact parasite
      diversity.

PMID- 30198492
TI  - Annular scaly plaque confined to presternal keloid treated with intralesional
      injections.

PMID- 30198493
TI  - Strawberry Notch 1 (SBNO1) promotes proliferation of spermatogonial stem cells
      via the noncanonical Wnt pathway in mice.
AB  - While it is known that spermatogonial stem cells (SSCs) initiate the production
      of male germ cells, the mechanisms of SSC self-renewal, proliferation, and
      differentiation remain poorly understood. We have previously identified
      Strawberry Notch 1 (SBNO1), a vertebrate strawberry notch family protein, in the
      proteome profile for mouse SSC maturation and differentiation, revealing SBNO1 is
      associated with neonatal testicular development. To explore further the location
      and function of SBNO1 in the testes, we performed Sbno1 gene knockdown in mice to
      study the effects of SBNO1 on neonatal testicular and SSC development. Our
      results revealed that SBNO1 is required for neonatal testicular and SSC
      development in mice. Particularly, in vitro Sbno1 gene knockdown with morpholino
      oligonucleotides caused a reduction of SSCs and inactivation of the noncanonical
      Wnt pathway, through Jun N-terminal kinases. Our study suggests SBNO1 maintains
      SSCs by promoting the noncanonical Wnt pathway.

PMID- 30198494
TI  - Resveratrol attenuates metabolic, sperm, and testicular changes in adult Wistar
      rats fed a diet rich in lipids and simple carbohydrates.
AB  - High-fat diets affect male reproduction and sexual function. Therefore, we
      evaluated the effects of prolonged resveratrol administration on the metabolic,
      sperm, and testicular parameters of rats fed a cafeteria diet. Male Wistar rats
      were divided at weaning into control (C, n = 20) and cafeteria (CAF, n = 16)
      groups. At 3 months, half of them were given daily supplementations of
      resveratrol (C-R, n = 10; CAF-R, n = 8) at a dosage of 30 mg kg-1 body mass for 2
      months. Animals were killed at 5 months of age, and blood, spermatozoa, and
      testes were collected for further analysis. Data were analyzed by one-way ANOVA,
      and P < 0.05 was considered statistically significant. The CAF diet promoted
      hyperglycemia (P < 0.0001), and treatment with resveratrol reversed this
      condition (P < 0.0001). The CAF diet reduced sperm viability and motility, while
      resveratrol improved these parameters (P < 0.05). Regarding testicular
      morphology, the height of the seminiferous epithelium was reduced in the CAF
      group compared with that of the C group (P = 0.0007). Spermatogenic cell
      proliferation was also reduced in the CAF group compared with that of the C
      group. However, the CAF-R showed an increase in cell proliferation rate compared
      with that of the untreated CAF group (P = 0.0024). Although it did not modify
      body mass, the consumption of a CAF diet promoted hyperglycemia, adverse
      testicular morphology remodeling, and abnormal sperm, which were attenuated by
      treatment with resveratrol, thus suggesting a protective effect of this
      antioxidant on spermatogenesis.

PMID- 30198495
TI  - Lycopene exerts anti-inflammatory effect to inhibit prostate cancer progression.
AB  - Lycopene is a natural compound that alleviates oxidative stress and inflammation,
      exerting therapeutic effects in a number of cancers. The aim of this study is to
      investigate the efficacy of lycopene in inhibiting prostate cancer. Cell
      viability assays indicated the dose- and time-dependent toxicity of lycopene in
      prostate cancer cells. Annexin V/propidium iodide double-staining assays revealed
      the strong apoptotic effects of lycopene. The levels of inflammatory factors,
      including interleukin-1 (IL1), IL6, IL8, and tumor necrosis factor-alpha (TNF
      alpha), in lycopene-treated cells were also reduced by lycopene treatment. With
      the increasing dose of lycopene, the survival of mice bearing prostate cancer
      xenografts was significantly improved (P < 0.01), and the tumor burden was
      significantly reduced (P < 0.01). Our results indicate that lycopene is a
      promising chemotherapy drug, which inhibits prostate cancer progression by
      suppressing the inflammatory response.

PMID- 30198496
TI  - Mean platelet volume might be an effective indicator of arterial erectile
      dysfunction.
AB  - The aim of our study was to investigate the role of platelet parameters including
      mean platelet volume (MPV) and platelet count (PC) in the pathogenesis of penile
      arteriogenic erectile dysfunction (ED) and to evaluate the association between
      the platelet parameters and arteriogenic ED. There were 244 patients with ED
      (based on the International Index of Erectile Function [IIEF]-5 <=21) and 60
      healthy controls (IIEF-5 >21) enrolled. All participants were asked to undergo a
      laboratory examination, and penile vascular function was evaluated using penile
      color Doppler ultrasonography (pDUS). Among these ED patients, 24 patients with
      no abnormality on nocturnal penile tumescence (NPT) and 84 with normal
      vasculature or mixed vascular abnormalities were excluded. The other patients
      were classified into three groups as follows: control (n = 60), arteriogenic ED
      (n = 99), and venous leakage (n = 37) groups. MPV and PC were significantly
      higher in the arteriogenic ED group compared with the venous and control groups
      (P < 0.05). Receiver operating characteristic curve analysis revealed that the
      area under the curve for MPV to predict arteriogenic ED was 0.707. MPV >=9.65 fl
      was recognized as a cut-off value for potential arteriogenic ED (sensitivity:
      47.5%; specificity: 91.7%). A significant inverse correlation was detected
      between MPV and 10-min peak systolic velocity (PSV) (r = -0.34; P < 0.001) in the
      arteriogenic ED group. These findings suggest that the MPV might be a powerful
      indicator to predict and diagnose arteriogenic ED, and MPV may be a marker for ED
      when using pDUS.

PMID- 30198497
TI  - Tuberculous gummas: Epidemiological, clinical, bacteriological, immunological,
      and therapeutic features.
AB  - Tuberculous gummas are an unusual form of tuberculosis (TB) accounting for 1%-2%
      of all cutaneous TB cases. The aim of this article was to describe the
      epidemiological, clinical, bacteriological, immunological, and therapeutic
      features of this form upon a case report and a literature review. Forty-eight
      case reports were identified through a PubMed and Google Scholar search using the
      following keywords: "tuberculous gumma" and "metastatic tuberculous abscesse."
      Tuberculous gumma can occur at any age. Immunodepression is not a sine qua non
      condition to the development of the disease. Limbs are the most frequent site for
      gummas. Tuberculous gummas are associated to another location in only 73% of
      cases. The most frequent associated locations are lung, nodes, and
      musculoskeletal apparatus. Mantoux test is negative in 38% of cases. Skin stain
      is positive in 45% of cases and culture in 85% of cases. Giant epithelioid cell
      granuloma is present in 82.4% of cases. There is no universally accepted
      chemotherapy regimen for metastatic tuberculous abscesses. The classic 2RHZE/4RH
      is highly effective.

PMID- 30198499
TI  - Mycobacterial inactivation protein extraction protocol for matrix-assisted laser
      desorption ionization time-of-flight characterization of clinical isolates.
AB  - Background: Rapid identification of mycobacteria has been made possible with
      matrix assisted laser desorption ionization time-of-flight (MALDI-TOF) in recent
      years. Working with high concentrations of mycobacteria in a PC-3 containment
      facility makes MALDI-TOF cumbersome and costly. Therefore removing the
      inactivated isolate's protein extract from the PC-3 facility is needed for
      efficient identification in a routine PC-2 laboratory. Methods: This work
      describes a novel chemical and mechanical disruption protein extraction method,
      which provides reliable MALDI-TOF results from solid and liquid media, while
      ensuring laboratory safety. Results: When compared to sequencing results, 93.9%
      of the clinical isolates were identified in LJ media and 89% of the clinical
      isolates were identified in MGIT media. Conclusion: The MIPE protocol produces a
      high quality protein extract with improved isolate identification without
      compromising result turn-around-times or laboratory safety.

PMID- 30198498
TI  - Cervical tuberculous lymphadenitis: Clinical profile and diagnostic modalities.
AB  - Background: Tuberculosis is a major global health problem. Tuberculous
      lymphadenopathy is a most common form of extrapulmonary tuberculosis (EPTB),
      constitutes 35% of all cases of EPTB. Due to the paucibacillary nature of
      specimens, smear microscopy and culture offer low sensitivity. Methods: The aim
      of the present study was to find the clinicodemographic profiles and comparing
      the performance of Xpert MTB/RIF, conventional polymerase chain reaction (PCR),
      mycobacteria growth indicator tube (MGIT) 960, histopathological examination, and
      clinical follow-up of patients in diagnosing of smear-negative tuberculous
      lymphadenopathy. Results: A total of 140 clinically suspected cervical
      tuberculous lymphadenitis cases were enrolled in this study. MGIT-960 culture,
      conventional PCR, and Xpert MTB/RIF were performed. Most of the patients
      presented with unilateral (87.14%), single (81.42%), matted (87.85%) lymph nodes,
      3 cm-6 cm (52.14%), commonly in the right side (68.02%), and associated lung
      lesion was found in 12.86% of cases. The detection rates of Mycobacterium
      tuberculosis complex (MTBC) by Xpert MTB/RIF, conventional PCR, and MGIT were
      25.71%, 20.71%, and 17.85%, respectively. Both the tests: Xpert MTB/RIF and PCR,
      PCR and MGIT, Xpert MTB/RIF and MGIT were positive in 15.71%, 15.71%, and 11.42%
      of cases, respectively. Most of the patients (74.1%) were cured with 6 months of
      antitubercular drugs. Conclusion: Clinicians often face the diagnostic dilemmas
      presented in the study. Individual modalities of the diagnosis are available, but
      all have drawbacks with varied sensitivity and specificity. Combining the
      available clinical, radiological, and microbiological modality to reach early
      diagnosis can go a long way to avoid misdiagnosis and unnecessary delay in
      treatment, especially in cases, without the pulmonary involvement and fulfilling
      the aim of National Tuberculosis Control Programme for EPTB cases.

PMID- 30198500
TI  - OMNIgene SPUTUM: A good transport and decontaminating reagent for tuberculosis
      testing.
AB  - Background: Sputum culture is limited to centralized facilities. Thus, samples
      require transportation from peripheral laboratories to these facilities,
      compromising specimen quality since it is difficult to maintain cold chain. We
      evaluated OMNIgene SPUTUM Reagent (OMS) for transporting sputum samples for
      tuberculosis (TB) testing. The study was carried out at Noguchi Memorial
      Institute for Medical Research using sputa from Korle Bu Teaching Hospital and La
      General Hospital in Ghana. Methods: In a laboratory-based controlled experiment
      (CE), sputum contaminants were determined on blood agar before treatment with OMS
      and N-acetyl-L-cysteine-sodium hydroxide (NALC-NaOH). TB testing included smear
      microscopy, culture, and Xpert MTB/RIF. Afterward, two peripheral laboratories
      were trained to transport sputum samples with OMS without cold chain. Positivity,
      negativity, and contamination rates were compared between both methods using Chi
      square and Fisher's exact tests. Cohen's Kappa was also used to determine
      agreements. Results: Among 104 sputum samples analyzed in the CE, 93 (89.4%) had
      bacterial growth on blood agar before decontamination, while 6 (5.8%) and 5
      (4.8%) contaminated after NALC-NaOH and OMS treatment, respectively.
      Contamination was high with NALC-NaOH (12.8%) than OMS (4.3%) on Lowenstein
      Jensen media (P < 0.001), but mycobacterial positivity was comparable: NALC-NaOH
      of 74.5% and OMS of 78.7%. Smear positivity after NALC-NaOH treatment was 89.4%
      and OMS was 75.9% (P = 0.491). All except one of the samples tested positive by
      Xpert MTB/RIF after both treatment. Sixteen samples were evaluated in the field
      experiment and 81.3% yielded positive culture, and no contamination on LJ was
      observed. Conclusion: Our findings indicate that OMS works well as a transport
      and decontaminating reagent of samples for TB testing.

PMID- 30198502
TI  - Molecular characterization of Mycobacterium tuberculosis isolates from pulmonary
      tuberculosis patients in Khartoum, Sudan.
AB  - Background: The aim of this study was to characterize the drug resistance
      profile, and the specific lineages of Mycobacterium tuberculosis (MTB) strains
      isolated from patients with pulmonary TB in the state of Khartoum in Sudan.
      Methods: Consecutive sputum samples and clinical data were collected from 406
      smear-positive TB patients with pulmonary TB in 2007-2009. The samples were
      cultured, and drug susceptibility testing (DST) was performed using the
      proportion method (PM) on solid Lowenstein-Jensen medium, and species were
      identified using biochemical methods at the National Reference Laboratory (NRL)
      in Khartoum. Extracted deoxyribonucleic acid from a total of 120, 60 suspected
      multidrug-resistant isolates (MDR), and 60 non-MDR isolates were subsequently
      sent to the WHO supranational reference laboratory (SRL) in Stockholm at the
      Public Health Agency of Sweden, for confirmation of the drug resistance profile,
      examinations by line probe assay (LPA), and molecular epidemiology analysis with
      Spoligotyping. Results: LPA results correlated 100% for non-MDR and 62% for the
      suspected MDR strains when compared to the DST results obtained by PM at the NRL.
      Two strains were initially using the PM identified as MDR-TB but later shown by
      Hain GenoType Mycobacterium CM/AS to belong Mycobacterium avium complex
      (Mycobacterium intracelluare). These two strains were excluded from the study
      material for further analysis. The remaining 58 MDR strains were analyzed using
      LPA, and 36 strains were confirmed as MDR, 10 as rifampicin monoresistant, and
      eight as isoniazid-monoresistant. Spoligotyping for all the 118 MTB isolates
      revealed a total of 115 patterns in which four patterns represented major
      clusters with a total of 108 (91%) of the strains. The CAS1_Delhi/family was the
      predominant type and detected in 62 isolates (52%), of which 26 were MDR and 36
      were susceptible. It was followed by H3/family with 19 (16%) strains, and 11
      Latin American Mediterranean3/family, 16 T2/T1, and two strains each of the
      Beijing and S lineage.  Conclusion: Comparison of DST results obtained using PM
      and LPA showed 100% agreement for the non-MDR strains but only 62% for the MDR
      strains. Taking in consideration the time, risk of contamination and the cost of
      labour to identify MDR TB, the LPA have clear advantages in early detection of
      MDRTB than the PM. Additionally in this study material Spoligotyping revealed the
      CAS1 Delhi as the most predominant family. We could not see no major difference
      in lineages between MDR and non-MDR strains.

PMID- 30198501
TI  - Effective pragmatic approach of diagnosis of multidrug-resistant tuberculosis by
      high-resolution melt curve assay.
AB  - Background: Effective management of multidrug-resistant tuberculosis (MDR-TB)
      requires cost-effective and rapid screening of rifampicin (RIF) and isoniazid
      (INH) resistance. Accordingly, a highly promising high-resolution melting (HRM)
      analysis was evaluated in the detection of mutation in rpoB, katG gene and inhA
      promoter region in Mycobacterium tuberculosis isolates. Methods: A total of 143
      M. tuberculosis isolates comprising phenotypically confirmed 94 MDR and 49
      sensitive isolates were analyzed by HRM following real-time-polymerase chain
      reaction in comparison to gold standard of targeted DNA sequencing of rpoB, katG
      gene and inhA promoter region. Results: HRM correctly identified MDR-TB by rapid
      and accurate detection of predominantly and infrequently occurring specific
      single nucleotide polymorphism in rpoB, katG gene and inhA promoter region. rpoB
      HRM showed sensitivity, specificity, positive predictive value (PPV) and negative
      predictive value (NPV) of 98% each respectively. Predominantly, S531 L/W (TCG ->
      TTG/TGG) mutation accounted for 68.47% of RIF resistance followed by H526Y/R
      (13.04%, CAC -> TAC/CGC), D516Y/V/G (10.86%, GAC -> TAC/GTC/GGC), Q513P (4.34%,
      CAA -> CCA), and one rare mutation at codon position L533A (CTG -> CGG). Combined
      KatG and inhA HRM sensitivity, specificity, PPV, and NPV were 90%, 100%, 100%,
      and 84.48% respectively and detected frequent mutation at codon position
      S315T/I/N (70%, AGC -> ACC, AGC -> ACT, AGC -> AAC) and rare mutation at codon
      position T314P (3.3%, ACC -> CCC) and 329 (2.2%, GAC -> GCC) of katG gene. In
      inhA, mutations were recorded at mostly promoter position - 15 (10%, C -> T) and
      infrequently at - 8 (3.3%, T -> G, T -> C). HRM assay limitation noticed in
      recognizing silent mutation in rpoB as a mutant, nondetection of infrequent
      mutation S310A in katG, and the inability of detecting mutation outside the
      targeted region of investigated genes. Conclusion: HRM may prove to be a vital
      molecular assay in rapid screening of TB cases for early detection of MDR TB,
      leading to early evidenced-based initiation of antitubercular treatment that will
      significantly reduce MDR transmission.

PMID- 30198503
TI  - Methylation status of alu repetitive elements in children with tuberculosis
      disease.
AB  - Background: Investigation of DNA methylation in Alu repetitive elements (REs) was
      shown to be a promising field to explore transcriptional changes in human genome
      under disease condition. To scrutinize the association between Alu methylation
      and tuberculosis (TB) disease in children, the difference in Alu DNA methylation
      level was compared with healthy controls. Methods: Whole-blood genomic DNA from
      36 TB-infected children and 32 healthy controls was isolated, and the level of
      Alu repeat DNA methylation was examined by methylation-specific polymerase chain
      reaction. Results: The median Alu methylation level in TB patients was 30%
      (Interquartile range [IQR], 25-30%), whereas in healthy controls, it was 75%
      (IQR, 50-75%) (P < 0.0001). The median level of DNA methylation of Alu RE in TB
      cases was significantly lower than healthy controls. Receiver operating
      characteristic curve analysis showed that the area under the curve for diagnosis
      was 0.969 (95% confidence interval, 0.936-1) (P < 0.0001), with 100% sensitivity
      and 84% specificity. Conclusion: Our results point out that detection of Alu DNA
      methylation in whole-blood DNA may be clinically useful tool for the diagnosis
      and prognosis of TB disease in children.

PMID- 30198504
TI  - Perception toward the disease of the people affected by leprosy.
AB  - Background: This study aimed to explore the disease severity perceived by people
      affected with leprosy reporting at leprosy referral center, Purulia, West Bengal,
      India. Methods: A cross-sectional study was conducted among 358 persons affected
      by leprosy above the age of 18 and married who were reporting at tertiary leprosy
      referral hospital, Purulia, West Bengal, India. A semistructured questionnaire
      was prepared to collect the demographic profile, disease profile, and perceived
      severity of the disease. Results: Among the participants, 41% of them were
      female, 60% were aged between 18 and 45 years, 58% were literate, and 40% of the
      participants had physical disability. The participants had multiple feelings of
      fear, anxiety and sorrow when first diagnosed as leprosy affected. Majority (69%)
      of the participants had fear of the disease. A significant association was
      present among males and females feeling fear of leprosy and the female feared
      more than male. Conclusion: The present study emphasizes the need for continuous
      counseling and health education for persons affected with leprosy to avoid or
      minimize the psychological problems. Periodical screening and counseling will
      improve their psychosocial well-being and quality of life.

PMID- 30198505
TI  - The etiology and public health significance of mycobacteriosis of cattle in
      Kenya.
AB  - Background: Zoonotic tuberculosis, commonly referred to as bovine, tuberculosis
      is mainly caused by Mycobacterium bovis subsp. bovis, a member of the
      mycobacterium tuberculosis complex (MTBC). Infection in humans resembles that
      caused by Mycobacterium tuberculosis. Mycobacteria Other Than Tuberculous (MOTTs)
      are also increasingly being associated with tuberculosis humans but reports of
      infections in animals are scarce, their zoonotic potential being largely ignored.
      The study aimed to determine the aetiology and public health importance of
      mycobacteriosis in slaughter cattle in Kenya. Methods: Routine postmortem meat
      inspection was performed on a subpopulation of 1000 meat carcasses selected
      randomly from among 7,564 in a municipal abattoir, between January and July,
      2015. Carcasses were examined for tuberculous lesions which were then examined
      for acid-fast bacilli, (AFB), cultured for isolation of mycobacteria and the
      isolates characterized by DNA analysis. Results: Of the carcasses examined, 218
      (21.8%) had lesions in various parts of the carcasses. Acid-fast bacilli were
      observed in 63/218 of the lesions and suspected mycobacteria isolated from 35 of
      them. The isolates were identified as M. fortuitum (12), M. bovis subsp. bovis
      (3), M. shimoidei (2) M. asciaticum, M. interjectuctum, M. szulgai, M. celatum
      and M. kansaasii at one (1) each. Thirteen (13) of the isolates could not be
      speciated. Conclusion: The MOTTs identified in the study have been liked to
      various types of mycobacteriosis in humans. The study therefore highlights the
      pathogenic and zoonotic potential of MOTTs, indicating that zoonotic tuberculosis
      should not be restricted to Mycobacterium bovis subsp.bovis.

PMID- 30198506
TI  - Interaction of South Asian spices with conventional antibiotics: Implications for
      antimicrobial resistance for Mycobacterium abscessus and cystic fibrosis.
AB  - Background: Antimicrobial resistance (AMR) has rendered certain species of
      Mycobacterium difficult to treat clinically, particularly, the nontuberculous
      Mycobacterium, Mycobacterium abscessus. This bacterium is emerging in specific
      disease populations, including amongst cystic fibrosis (CF) patients, where AMR
      represent a true treatment dilemma. Therefore, any innovation with traditional
      antimicrobial compounds in spices, which increases the potency of existing
      conventional antibiotics should be investigated. Methods: M. abscessus isolates
      (n = 9 multidrug-resistant clinical isolates from CF patients + 1 Reference
      Strain) were examined for their direct susceptibility to 27 spices, as well as
      the interactive effect of this spice combination to their susceptibility to
      amikacin and linezolid antibiotic, with standard disk diffusion assay. Results:
      Five isolates of M. abscessus (5/10; 50%) failed to grow on the spice enriched
      medium, which included four clinical isolates and the National Culture Type
      Collection (NCTC) Reference Strain. Of the remaining five isolates which grew on
      the spice medium, no cultural phenotypic differences were observed, compared to
      unsupplemented controls. In the case of both amikacin and linezolid, the zone of
      inhibition increased with the inclusion of the spices. Initially, all isolates of
      M. abscessus were fully resistant to linezolid (mean zone of inhibition = 0 mm),
      and growth was to the edge of the antibiotic disk, whereas when in the presence
      of spices, large zones of inhibition were observed (mean zone of inhibition =
      33.3 mm). With amikacin, the mean zone of inhibition increased from 23.2 mm to
      32.0 mm, in the presence of spices. Conclusion: These data suggest that the
      spices were interacting synergistically with the antibiotics, thus making the
      antibiotic more potent against the bacteria tested. This study is significant as
      it demonstrates a positive interaction between spices and the conventional
      antimycobacterial antibiotics, amikacin, and linezolid. Given the burden of AMR
      to M. abscessus, particularly in a patient with chronic disease such as CF, any
      food-related innovation that can help maximize the potency of existing
      antimycobacterial antibiotics is to be encouraged and developed. The specific
      mechanism as to how spices increase the potency of such antibiotics with M.
      abscessus needs to be elucidated, as well as novel food (spice) delivery
      modalities developed, including novel medicinal foodstuffs or functional foods,
      that can harness this beneficial effect in vivo to medicine and society.

PMID- 30198507
TI  - Pediatric pleural tuberculosis.
AB  - Background: Pleural tuberculosis (TB) diagnosis is sometimes controversial
      because the microbiologic confirmation ratio is very low in pleural fluid. There
      are few pediatric pleural TB case series in the literature. Methods: We
      retrospectively evaluated our TB cases below 18 years of age and extracted
      pleural TB cases. Results: Seven cases with pleural TB were identified. About
      42.9% of the patients had isolated pleural TB whereas 57.1% of the patients had
      accompanying pulmonary TB. Lymphocytic pleural effusion and increased adenosine
      deaminase (ADA) (>40 U/L) level are found in 85.7% of the patients. Six patients
      had uncomplicated effusion (transudate) according to Light's criteria and one had
      complicated effusion (exudate). Lung decortication was needed in three patients.
      All patients were given 6 months anti-TB medication and recovered completely.
      Conclusion: In the lymphocyte-predominant pleural effusion, an increased ADA
      level highly supported TB disease. The complicated effusion (exudate) in pleural
      TB is not rule; uncomplicated effusion (transudate) could be seen.

PMID- 30198508
TI  - Antimycobacterial activity of veterinary antibiotics (Apramycin and Framycetin)
      against Mycobacterium abscessus: Implication for patients with cystic fibrosis.
AB  - Background: Antimicrobial resistance has rendered certain species of
      Mycobacterium difficult to treat clinically, particularly the nontuberculous
      Mycobacterium and Mycobacterium abscessus. While veterinary medicine and human
      medicine share many classes of antibiotics, there are several antibiotics which
      are uniquely licensed to veterinary medicine but not human medicine. It was,
      therefore, the aim of this study to examine the action of eight veterinary
      antibiotics to a population of multi- and pan-resistant M. abscessus, isolated
      from the sputum of patients with cystic fibrosis (CF). Methods: Antibiotic
      susceptibility studies were performed on human clinical isolates of M. abscessus
      (n = 16), including 11 smooth isolates, 4 rough isolates, and 1 reference isolate
      (NCTC 13031), against the following 7 veterinary antibiotics (antibiotic class):
      apramycin (aminoglycoside), cefovecin (cephalosporin), ceftiofur (cephalosporin),
      framycetin (aminoglycoside), lincomycin (lincosamide), pirlimycin (lincosamide),
      and spectinomycin (aminocyclitol). Results: M. abscessus isolates were sensitive
      (100%) to apramycin and framycetin but resistant (100%) to cefovecin, ceftiofur,
      lincomycin, pirlimycin, and spectinomycin. Conclusion: This study identified that
      the veterinary aminoglycosides, apramycin, and framycetin, have in vitro activity
      against multi-resistant clinical isolates of M. abscessus. Further studies should
      now compare the activity of these antibiotics against amikacin and the human
      aminoglycoside, advocated in the treatment of disease in CF patients, to
      determine if these novel antibiotics have a future role for the development in
      human medicine with such chronic disease patients.

PMID- 30198509
TI  - Insight to the molecular mechanisms of the osmolyte effects on Mycobacterium
      tuberculosis pyrazinamidase stability using experimental studies, molecular
      dynamics simulations, and free energy calculation.
AB  - Background: In this study, we have experimentally investigated the effects of
      different osmolytes including sucrose, sorbitol, urea, and guanidinium chloride
      (GdmCl) on the stability and structure of the Mycobacterium tuberculosis
      pyrazinamidase (PZase). PZase converts pyrazinamide to its active form. Methods:
      In addition, in order to gain molecular insight into the interactions between
      osmolytes and PZase, we have conducted 1000-ns molecular dynamics simulations.
      Results: The results indicated that sucrose and sorbitol increase the stability
      and compactness of the enzyme, whereas in the presence of urea and GdmCl, PZase
      loses its stability and compactness. Furthermore, the activity of PZase in the
      presence of sucrose was more than the other solutions. The energetic analyses
      imply that the electrostatic and van der Waals interactions are the major factors
      in the osmolyte-PZase interactions. Sorbitol and sucrose, as protective
      osmolytes, protect the protein structure by utilizing the van der Waals
      interaction from denaturation. In addition, urea molecules affect the structure
      of the protein using the hydrogen bonds and van der Waals interactions.
      Conclusion: The results show that the most important factor in the denaturing
      effect of GdmCl is the strong interactions of positively charged guanidinium ions
      with the aspartate and glutamate residues.

PMID- 30198510
TI  - A novel inexpensive electrochemical sensor for pyrazinoic acid as a potential
      tool for the identification of pyrazinamide-resistant Mycobacterium tuberculosis.
AB  - Introduction: Tuberculosis (TB) is a significant cause of morbidity and mortality
      worldwide. The patient compliance with the long treatment regimens is essential
      for successful eradication. Pyrazinamide (PZA) shortens these regimens from 9 to
      6 months, and therefore, improves treatment completion rates. Although PZA is a
      first-line medication for the treatment of TB, no simple or reliable assay to
      determine PZA resistance is yet available. In the presence of PZA, only
      susceptible Mycobacterium tuberculosis strains release pyrazinoic acid (POA).
      Therefore, the measurement and quantification of released POA is an indicator of
      PZA resistance. Methods: Two electrochemical sensors were constructed and tested
      with alternative working electrodes in conjunction with a portable potentiostat
      to measure the current produced when a potential difference of 2 V is applied to
      varying concentrations of POA in controlled solutions. Results: The large (13.2
      mm) electrochemical sensor was able to detect POA at a minimum concentration of
      40 MUM to a statistically significant level (P = 0.0190). Similar graphical
      trends were obtained when testing the electrochemical sensor in the supernatant
      of a negative microscopic observation drug susceptibility assay culture,
      irrespective of the presence of PZA. Conclusion: Inexpensive and reusable
      electrochemical sensors with a portable potentiostat are a promising tool for the
      detection of POA, a biomarker of PZA susceptible M. Tuberculosis.

PMID- 30198511
TI  - Chyluria: A rare initial manifestation of disseminated tuberculosis.
AB  - Chyluria is described as passage of chyle in the urine. It results from the
      formation of lymphaticorenal fistulae due to various etiologies. The most common
      implicated cause is filariasis especially in endemic areas. Other uncommon causes
      include thoracic duct trauma or anatomical abnormalities, pregnancy, malignancy,
      and tuberculosis. Although tuberculosis has been included as a cause, there are
      only a few case reports suggesting it as an etiology. Tuberculosis can present in
      various ways. However, chyluria as initial presentation of tuberculosis has never
      been reported in the literature. We present, here, an extremely rare case of
      disseminated tuberculosis involving lung, lymph nodes, liver, intestine, and
      spine presenting as chyluria. The patient responded dramatically with
      antituberculous therapy with complete clearing of urine.

PMID- 30198512
TI  - The paradoxical evolution in an unusual case of disseminated tuberculosis:
      Spontaneous resolution with disease progression.
AB  - Mycobacterium tuberculosis can cause a myriad of clinical manifestations. We
      describe a case of a patient with end-stage renal failure, who presented with
      disseminated tuberculosis over the course of five months, manifesting with a self
      resolving mediastinal mass, progressive lymphadenopathy, genitourinary, and
      musculoskeletal tuberculosis.

PMID- 30198513
TI  - Various cutaneous tuberculosis with rare clinical manifestations: A case series.
AB  - Cutaneous tuberculosis (TB) has several clinical manifestations. The most common
      forms include cervical scrofuloderma and plaque type of lupus vulgaris (LV),
      otherwise the rare cases including inguinal scrofuloderma, ulcerative LV, and
      acute miliary TB. The highlight of this case series was to report various rare
      clinical manifestations of cutaneous TB.

PMID- 30198515
TI  - Pulmonary functions' assessment in posttuberculosis cases by spirometry:
      Obstructive pattern is predominant and needs cautious evaluation in all treated
      cases irrespective of symptoms.

PMID- 30198514
TI  - Tuberculosis of radius diaphysis: Case report and review of literature.
AB  - Diaphyseal tuberculosis (TB) is a rare case of the skeletal TB. The following
      report documents the case of a 52-year-old Moroccan woman with a swelling over
      the right forearm followed by pulmonary TB under treatment for 3 months. The
      radiographs of the forearm show a lytic image located at the radius mid
      diaphysis. The histopathology confirmed the diagnosis. The patient received
      surgical drainage with trepanation of the bone. The antibacillary chemotherapy
      was administered for 6 months. It is, therefore, indispensable to bear in mind
      the possibility of such atypical presentations of TB when making a rapid and
      pertinent diagnosis and prescribing the appropriate treatment.

PMID- 30198516
TI  - Double trouble: Mediastinal lymph nodal tuberculosis complicated by amyloidosis
      and esophago-nodal fistula after endoscopic ultrasound fine-needle aspiration.

PMID- 30198518
TI  - Associations between congenital heart defects and genetic and morphological
      anomalies. The importance of prenatal screening.
AB  - AIM: To study congenital heart defects (CHDs), evaluate their relation to extra
      cardiac pathologies, and assess the significance of prenatal diagnostics for
      heart diseases. METHODS: Data from 1999-2017 were analyzed for the incidence of
      significant CHDs in fetuses (prenatal ultrasound/echocardiography) and children,
      including, where applicable, autopsy data and genetic evaluation. RESULTS: Among
      220,400 fetuses, 819 (3.7 cases per 1000) significant CHDs were observed. Of the
      total, 53% (435/819) of CHDs were diagnosed prenatally. The heart defect was an
      isolated impairment in 78% (640/819), associated with a genetic impairment in 16%
      (128/819), and with extra-cardiac malformations without genetic pathology in 6%
      (51/819). Chromosomal aberrations were diagnosed prenatally in 70% (90/128) of
      those affected and extra-cardiac conditions in 86% (44/51). The CHD and genetic
      pathology association was more frequent prenatally [21% (90/435) vs. postnatally:
      10% (38/384; P<0.0001)], as was the association between CHD with other extra
      cardiac pathology and a normal karyotype [prenatally: 10% (44/435) vs.
      postnatally: 2% (7/384; P<0.0001)]. CONCLUSION: Heart defects are most frequently
      isolated, with genetic and other extra-cardiac anomalies in about one third of
      cases, significantly linked to prenatal diagnostics.

PMID- 30198517
TI  - A Prognostic Nomogram for Disease-Specific Survival in Patients with Pancreatic
      Ductal Adenocarcinoma of the Head of the Pancreas Following
      Pancreaticoduodenectomy.
AB  - BACKGROUND This study developed and validated a nomogram to predict patient
      prognosis for pancreatic ductal adenocarcinoma (PDAC) of the head of the pancreas
      following pancreaticoduodenectomy. MATERIAL AND METHODS Retrospective data were
      obtained from 4,383 patients with PDAC of the head of the pancreas who underwent
      pancreaticoduodenectomy between 2004-2013 from 11 Registries Research Data of the
      Surveillance, Epidemiology,and End Results (SEER) database. Cox proportional
      hazards model was used to identify independent risk factors. The predictive
      accuracy of the nomogram was determined by the concordance index (C-index) and
      calibration curve. The results were externally validated by comparison with data
      from 1,743 patients from 7 other Registries Research Data. RESULTS Of the 4,383
      patients in the training dataset, median disease-specific survival (DSS) was 17.0
      months (range, 1.0-131 months), and postoperative 1-year, 3-year, and 5-year DSS
      rates were 70.3%, 26.1%, and 16.8%, respectively. Multivariate analysis showed
      that patient sex, age, tumor grade, regional lymph nodes examined, positive
      regional lymph nodes, tumor size, extent of local invasion, and tumor metastases
      were independent risk factors for DSS. The C-index of the internal validation
      dataset for prediction of DSS was 0.64 (95% CI, 0.63-0.65), which was superior to
      the American Joint Committee on Cancer (AJCC) staging, 0.57 (95% CI, 0.56-0.58)
      (P<0.001). The 5-year DSS rates and median DSS time for patients in the low-risk
      group were significantly greater compared with high-risk group (P<0.001).
      CONCLUSIONS A validated prognostic disease-specific nomogram for patient survival
      in PDAC of the head of the pancreas following pancreaticoduodenectomy was
      developed.

PMID- 30198519
TI  - Serum C-peptide level correlates with the course of muscle tissue healing in the
      rabbit model of critical limb ischemia.
AB  - AIM: The therapeutic potential of adipose-derived stem cell conditioned medium
      (ASC-CM) was studied in the rabbit model of critical limb ischemia (CLI).
      METHODS: Rabbits received treatment with ASC-CM or placebo. Gastrocnemius muscle
      tissue was collected 35 days after ischemia induction. Ischemic changes were
      evaluated in hematoxylin-eosin stained tissues for early (necrotic
      lesions/granulation tissue) and late (fibrous scars) phases of tissue repair. The
      expression of proangiogenic miR-126 was also evaluated using in situ
      hybridization. The levels of cytokines, insulin, and C-peptide were measured in
      blood. RESULTS: Early repair phases were observed more often in placebo-treated
      samples (45.5%) than in ASC-CM-treated ones (22.2%). However, the difference was
      not statistically significant. We demonstrated a statistically significant
      positive correlation between the early healing phases in tissue samples and C
      peptide levels in peripheral blood. The expression of proangiogenic miR-126 was
      also shown in a number of structures in all phases of ischemic tissue healing.
      CONCLUSION: Based on our results, we believe that treatment with ASC-CM has the
      potential to accelerate the healing process in ischemic tissues in the rabbit
      model of CLI. The whole healing process was accompanied by miR-126 tissue
      expression. C-peptide could be used to monitor the course of the tissue healing
      process.

PMID- 30198520
TI  - Therapeutic plasma exchange in secondary prevention of acute pancreatitis in
      pregnant patient with familial hyperchylomicronemia.
AB  - INTRODUCTION: Hormone changes during pregnancy lead to increased plasma lipid
      levels. When there is added disorder of lipid metabolism, this otherwise
      physiological change can cause extremely high triglyceride levels with
      potentionally life-threatening complications, such as non-biliary acute
      pancreatitis. MATERIALS AND METHODS: We present a case report of a 27-year-old
      pregnant woman with familial hyperchylomicronemia and a history of 7
      hypertriglyceridemia-induced acute pancreatitis attacks. Three attacks occured
      during her first pregnancy with the last one leading to its termination at 33
      weeks owing to the death of the fetus. During her second pregnancy, standard
      treatment was not able to lower the triglyceride levels sufficiently and she
      suffered another acute pancreatitis attack. Therapeutic plasma exchange was
      therefore chosen as the treatment method. RESULTS AND CONCLUSION: Plasma exchange
      was succesful in the secondary prevention of acute pancreatitis attack and she
      delivered a healthy baby at 36 weeks of gestation. Treatment was very well
      tolerated by the mother and the fetus and this supports the use of apheresis as a
      safe and efficient method in tackling gestational hypertriglyceridemia.

PMID- 30198521
TI  - Ciprofloxacin prophylaxis during autologous stem cell transplantation for
      multiple myeloma in patients with a high rate of fluoroquinolone-resistant gram
      negative bacteria colonization.
AB  - BACKGROUND: Ciprofloxacin prophylaxis used to be a standard precaution during
      autologous stem cell transplantation. Its benefit, with a high prevalence of
      fluoroqinolone resistance in the population, has recently been under scrutiny.
      OBJECTIVE: To evaluate the impact of cessation of ciprofloxacin prophylaxis
      during stem cell transplantation for multiple myeloma. PATIENTS AND METHODS: Data
      from 104 patients with multiple myeloma transplanted during the period from
      January 2013 to April 2015 were retrospectively reviewed. 67 received standard
      ciprofloxacin prophylaxis (group A) and 37 received no antibacterial prophylaxis
      (group B). RESULTS: Febrile episodes during neutropenia, bloodstream infection
      (BSI) and mortality in these two cohorts were evaluated. Gram negative BSI was
      assessed for the colonization of quinolone-resistant gram-negative pathogens.
      Secondary Clostridium difficile enterocolitis presence was determined in both
      cohorts. There were 42 (63%), 7 (10%), and 0 febrile episodes, BSI and gram
      negative BSI respectively in group A, and 34 (92%), 12 (32%), and 4 (11%)
      respectively in group B. The differences in the number of febrile episodes
      (P=0.0011) and deaths (P=0.0427) were statistically significance. Mortality was 0
      and 3 (8%) in group A and group B, respectively. There was no significant
      difference in colonization with quinolone-resistant gram negative pathogens (25
      (37%) versus 11 (30%)) between groups. The occurrence of Clostridium difficile
      colitis was the same in both groups. CONCLUSION: We resumed ciprofloxacin
      prophylaxis for the following reasons. There was a significant reduction in
      febrile episodes, and consequently a sparing effect of antibiotics used for
      treatment of this condition. No difference in Clostridium difficile colitis
      occurred and the mortality rate of 8% in group B was unacceptably high.

PMID- 30198522
TI  - Diatoms response to salinity changes: investigations using single pulse and cross
      polarisation magic angle spinning 29Si NMR spectra.
AB  - Diatoms Thalassiosira pseudonana and Chaetoceros muelleri (Bacillariophyceae)
      were cultured at three different salinities (26, 36 and 46 practical salinity
      units (PSU)) and their silica content examined using natural abundance 29Si magic
      angle spinning (MAS) nuclear magnetic resonance (NMR) spectroscopy. The samples
      were investigated using both single pulse (SP) and cross-polarisation (CP) MAS
      experiments. In addition, samples of T. pseudonana were examined using variable
      contact time CP MAS experiments allowing the dynamics (TSiH and T1rrhoH) of CP to
      be determined. Comparison of SP and CP results revealed a change to a less
      condensed silica state when diatoms were cultured at salinities away from optimal
      (36 PSU). Further, an increased amount of organic material (but not its
      composition) was determined to be present for such samples affecting CP
      experiments. The location of the organic material, on the diatom surface or
      within the frustule, was unable to be determined.

PMID- 30198528
TI  - Probing the structural and electronic properties of zirconium doped boron
      clusters: Zr distorted B12 ligand framework.
AB  - As an extension of boron based materials, transition-metal doped boron clusters
      deserve interest in controlling size-dependent structural and electronic
      properties. Herein, using the Crystal structure AnaLYsis by Particle Swarm
      Optimization (CALYPSO) method and density functional theory (DFT) calculations,
      we have performed a global search for the lowest-energy structures of ZrBQn (Q =
      0, -1) clusters with n = 10-20. The results show that the ground-state structures
      of the obtained clusters feature a distinctive structural evolution pattern, from
      half-sandwich bowl to distorted drum-like and then to Zr-centered distorted
      tubular motifs. For the sake of validating the current ground-state structures,
      photoelectron spectra are predicted from time-dependent DFT calculations. More
      interestingly, the neutral and anionic ZrB12 clusters are found to possess
      enhanced stability in the size regime studied here. The stability of the closed
      shell half-sandwich ZrB12 cluster is analyzed by intrinsic bond orbital (IBO) and
      Adaptive Natural Density Partitioning (AdNDP) methods, which indicates that the
      stability mechanism is caused by the dopant Zr atom breaking the boron bowl's
      triangle B3 unit to form a quasi-linear B3 unit in B12 and strengthen both the
      interaction of the B-B sigma-bonds and the Zr-B pi-bonds.

PMID- 30198529
TI  - Self-assembly of two-dimensional structures in water from rigid and curved
      amphiphiles with a low molecular weight.
AB  - Two-dimensional structures in water were self-assembled from rigid and curved
      amphiphiles with very low molecular weight (MW < 500 Da). The amphiphiles contain
      a bisnaphthalene core. Their structures have been characterized using 1H NMR
      spectroscopy, SEM, TEM, AFM, and DLS. The driving force was mainly attributed to
      hydrophobic effects.

PMID- 30198530
TI  - Quantitative structure-property relationship approach to predicting xylene
      separation with diverse exchanged faujasites.
AB  - Streamlining the xylene separation process on faujasites is a promising way to
      design innovative adsorbents for this application. For this purpose, we present
      herein an original quantitative structure-property relationship (QSPR) approach.
      It deals with the development of a multi-linear predictive model correlating the
      separation properties with a set of structural descriptors for the adsorbents.
      The implementation of such an approach makes it necessary to (i) set an
      appropriate design of experiment (DOE), (ii) prepare an adsorbent database, (iii)
      test the adsorbent database for xylene separation and (iv) compute a set of
      relevant descriptors. The selected descriptors essentially characterize the
      nature of the confinement in the faujasite supercage, i.e., the size of the
      cations localized in adsorption sites II, as well as the occupancy ratio of both
      adsorption sites II and III. Two different statistical methods were applied to
      develop a structure-property relationship model linking experimental selectivity
      and the set of descriptors. A multiple linear regression model enables the
      prediction of para/meta-xylene selectivity with a correlation coefficient R2 of
      0.78, while a linear discriminant analysis predicts the assignment of the
      adsorbents to four identified classes with a total prediction percentage of 76%.

PMID- 30198531
TI  - The first thieno[3,4-b]pyrazine based small molecular acceptor with a linear A2
      A1-D-A1-A2 skeleton for fullerene-free organic solar cells with a high Voc of
      1.05 V.
AB  - The first thieno[3,4-b]pyrazine (TP) based non-fullerene acceptor was synthesized
      and named as TP21, which shows a narrow band gap of 1.65 eV and a high-lying LUMO
      of -3.61 eV. Organic solar cells based on J61:TP21 realized a moderate power
      conversion efficiency (PCE) of 5.81% with a high open-circuit voltage (Voc) of
      1.05 V.

PMID- 30198533
TI  - Li+-Induced fluorescent metallogel: a case of ESIPT-CHEF and ICT phenomenon.
AB  - A fluorescent metallogel (1% w/v) has been synthesized from non-fluorescent
      ingredients viz. the smallest possible low molecular weight aromatic symmetrical
      ligand H2SA (1) and LiOH in a chloroform and methanol mixture. The chelation of
      Li+ is not only responsible for the inhibition of excited state intramolecular
      proton transfer (ESIPT) or the origin of fluorescence through chelation enhanced
      fluorescence (CHEF) in 1, but also for aggregation leading to gelation. The
      metallogel obtained from 1/Li+ reveals a fibrous morphology while 1 with other,
      bigger size, alkali metal ions like Na+/K+/Cs+ demonstrates the growth of
      crystals with different shapes. The effect of the size of the alkali metal ion
      over gel formation is well explored by FTIR, UV-vis, fluorescence, average
      lifetime measurements, SEM and PXRD. The metallogel shows multi-stimuli
      responsive behaviour towards thermal and mechanical stress as well as reswelling
      properties. The regioisomer H2PBA (2) also shows emission upon treatment with
      LiOH due to the presence of intramolecular charge transfer (ICT), this is well
      established by various experiments. The mechanism of gel formation is well
      established by FTIR, 1H NMR, UV-vis, fluorescence, lifetime measurements, SEM and
      single crystal and powder XRD instrumental techniques. The involvement of various
      phenomena in gel formation has been further supported by other synthesized model
      compounds viz. H2MBA (3), PMO (4), H2SEA (5) and H2SPA (6). True gel phase
      material is proved by detailed rheological experiments.

PMID- 30198535
TI  - Binary mixtures of novel sulfoxides and water: intermolecular structure, dynamic
      properties, thermodynamics, and cluster analysis.
AB  - Higher molecular weight dialkyl sulfoxides attract interest in the context of
      biomedical sciences due to their ability to penetrate phospholipid bilayers,
      dissolve drugs, and serve as cryoprotectants. Intermolecular interactions with
      water, a paramount component of the living cell, determine the performance of the
      sulfoxide-based artificial systems in their prospective applications. Herein, we
      simulated a wide composition range of sulfoxide/water mixtures, up to 85 w/w%
      sulfoxide, using classical molecular dynamics to determine structure, dynamics,
      and thermodynamics as a function of the mixture composition. As found, both
      diethyl sulfoxide (DESO) and ethyl methyl sulfoxide (EMSO) are strongly miscible
      with water. DESO- and EMSO-based aqueous mixtures exhibit similar structure and
      thermodynamic properties, however, quite different dynamic properties over the
      entire range of compositions. Strong deviations from an ideal mixture of between
      30-50 mol% (based on molar volume) of sulfoxide content lead to relatively high
      dynamic viscosities of the mixtures. The free energy of mixing with water is only
      slightly more favorable for EMSO than for DESO. The results, for the first time,
      quantify high miscibilities of both sulfoxides with water and motivate
      comprehensive in vivo investigation of the proposed mixtures.

PMID- 30198534
TI  - A new concept of a transparent photocapacitor.
AB  - A solid-state transparent photocapacitor has been prepared for the first time by
      the use of two transparent electrodes (TiO2 and LiFeO2) and also a transparent
      ion gel-based electrolyte between them, reaching a transmittance of 57% at lambda
      = 555 nm, a specific capacitance of 2.98 MUF cm-2 and a specific energy of 0.54
      MUJ cm-2.

PMID- 30198537
TI  - Editor's choice: underappreciated science.

PMID- 30198536
TI  - Time-gated triplet-state optical spectroscopy to decipher organic luminophores
      embedded in rigid matrices.
AB  - Wet-chemically synthesized inorganic materials often exhibit luminescence
      behavior. We have recently shown that the amorphous yttrium-aluminium-borate (a
      YAB) powders obtained by sol-gel and modified Pechini methods exhibit organic
      impurities, responsible for their intense visible photoluminescence and
      phosphorescence afterglow. However, the heterogeneity of impurity organic
      compounds and difficulties in their intact extraction from the solid inorganic
      host matrix limit the extraction-based chemical analysis for luminophore
      identification. Here, we propose a photo-physical route based on time-gated
      triplet-state optical spectroscopy (TGTSS) to construct the electronic structures
      of the trapped unknown luminophores, which successfully illustrates the
      luminescence properties of a-YAB powders in more detail and also provides
      important insights intrinsic to the nature of the luminophores. The experimental
      results accompanied with TD-DFT calculations of the theoretical electronic
      structures thus help us to propose the probable luminophore compounds trapped in
      rigid a-YAB matrices. We anticipate that the present approach will open new
      opportunities for analyzing similar complex luminescent materials, including
      carbon dots, graphene oxides, etc., which is vital for their improvement.

PMID- 30198538
TI  - Heterogeneous catalytic water oxidation controlled by coordination geometries of
      copper(ii) centers with thiolato donors.
AB  - Treatment of a penicillaminato platinum(ii) metalloligand with Cu2+ gave an S
      bridged PtII2CuII2 complex, which reacted with Zn2+ to produce 1D and 3D
      (PtII2CuII2ZnII)n coordination polymers, depending on the counter anions. These
      compounds increased heterogeneous electrocatalytic activities for water oxidation
      in proportion to the number of vacant coordination sites at thiolato dicopper(ii)
      cores.

PMID- 30198539
TI  - Distribution of zwitter-ionic tryptophan between the micelles of 1-dodecyl-3
      methyl imidazolium and aqueous medium from molecular dynamic simulation.
AB  - Ionic liquids that form micelles have great potential as drug carriers and
      separating agents for bioactive substances. For such applications, a key issue is
      the distribution of the target substance between the micelle and its environment.
      We perform MD simulations to study solubilization of zwitter-ionic tryptophan in
      micelles of 1-dodecyl-3-methylimidazolium bromide. We found that the distribution
      of tryptophan depends strongly on the degree of counterion binding. A decrease in
      binding of bromide counterions leads to a substantial increase of the
      distribution coefficient. A dense layer of counterions at the micellar surface
      impedes the solubilization of the zwitter-ionic tryptophan but at the same time
      the presence of such a dense layer obstructs the washout of the solubilized
      tryptophan molecules from the micelle. Based on our simulation data, we conclude
      that an increase of the distribution coefficient of tryptophan between the
      micelle and water may be achieved by several means: by introducing counterions
      that bind weakly to the micelle (bulky ions whose charge is not strongly
      localized) and/or by employing micelle-forming ionic liquids with shorter alkyl
      chains to diminish the degree of counterion binding.

PMID- 30198542
TI  - High-fidelity spectroscopy reconstruction in accelerated NMR.
AB  - Non-uniform sampling significantly accelerates the data acquisition time in NMR
      spectroscopy, but spectra must be reconstructed with appropriate methods. A high
      fidelity reconstruction method is proposed to preserve low-intensity spectral
      peaks and provide stable reconstruction under different sampling trials.

PMID- 30198544
TI  - Bis(chlorogermyliumylidene) and its significant role in elusive reductive
      cyclization.
AB  - Bis(chlorogermyliumylidene) 2 has been strategically obtained within redox-active
      bis(alpha-iminopyridine). Metal-free reduction of 2 followed by protonation led
      to elusive 2,3-di(pyridin-2-yl)piperazine with meso-stereoselectivity. Formation
      of persistent triplet diradicals upon reduction and isolation of piperazine
      stabilized Ge(ii) dication intermediates provide convincing evidence for the
      crucial role of [GeCl]+ units in reductive cyclization.

PMID- 30198543
TI  - Tailoring water stability of cellulose nanopaper by surface functionalization.
AB  - Cellulose nanopaper (CNP) features appealing properties, including transparency,
      flatness, a low thermal expansion coefficient and thermal stability, often
      outperforming conventional paper. However, free-standing crystalline cellulose
      films usually swell in water or upon moisture sorption, compromising part of
      their outstanding properties. This remains a major problem whenever working in a
      water environment is required. Freestanding cellulose nanopaper is prepared by
      solution casting water suspensions of cellulose nanocrystals with an average
      width of 10 nm and an average aspect ratio of 28, isolated from Avicel by acid
      hydrolysis and extensively characterized by AFM and FE-SEM measurements and GPC
      detection of their degree of polymerization. We demonstrate by elemental
      analyses, FT-IR, Raman spectroscopy, XRD measurements and water contact angle
      detection that wet treatment with lauroyl chloride results in surface
      hydrophobization of nanopaper. The hydrophobized nanopaper, C12-CNP, shows a more
      compact surface morphology than the starting CNP, due to the effect of chemical
      functionalization, and presents enhanced resistance to water, as assessed by
      electrochemical permeation experiments. The new hydrophobized nanopaper is a
      promising substrate for thin film devices designed to work in a humid
      environment.

PMID- 30198545
TI  - Oriented external electric fields as mimics for probing the role of metal ions
      and ligands in the thermal gas-phase activation of methane.
AB  - In the course of combined computational and mass spectrometry-based mechanistic
      studies, recently we came across rather unusual, if not unprecedented, effects of
      transition-metal ions and ligands when simple metal oxides or carbides are
      subjected to thermal gas-phase reactions with methane. Interestingly,
      "Gedankenexperiments" demonstrate how these effects can be modeled using oriented
      external electric fields (OEEFs), thus expanding their predicted role as "smart
      reagents" (Shaik et al., Nat. Chem., 2016, 8, 1091), and further suggesting that
      the OEEFs may be used in controlling the adsorption/desorption behavior of
      methane as well as serving as a tool to explore mechanistic features.

PMID- 30198546
TI  - Metallic carbide nanoparticles as stable and reusable substrates for sensitive
      surface-enhanced Raman spectroscopy.
AB  - We demonstrate for the first time that metallic carbide nanoparticles with a
      strong localized surface plasmon resonance (LSPR) effect could be used as SERS
      substrates to detect trace substances. They achieve a noble metal-comparable
      enhancement factor of 6.4 * 107.

PMID- 30198547
TI  - The neutrophil-to-lymphocyte ratio and mean platelet volume can be associated
      with severity of valvular involvement in patients with acute rheumatic carditis.
AB  - OBJECTIVE: The aim of the study was to investigate the association between the
      severity of acute rheumatic carditis (ARC) and the neutrophil-lymphocyte ratio
      (NLR) and mean platelet volume (MPV). METHODS: Paediatric patients diagnosed with
      ARC between 2010 and 2016 and age- and gender-matched controls were
      retrospectively analysed. At the time of diagnosis, we reviewed the demographic
      features obtained: echocardiographic data, complete blood count reports, acute
      phase reactants, including C-reactive protein, and erythrocyte sedimentation rate
      values. The patient group was further divided into two subgroups according to the
      degree of valvular regurgitation, which included those with severe and those with
      mild-to-moderate valvular regurgitation. RESULTS: The number of cases with ARC
      and age- and gender-matched controls were 120 and 50, respectively. The mean age
      of the patients was 12.25 +/- 2.89 (range: 7-18) years. NLR, MPV, anti
      streptolysin-O, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR),
      haemoglobin level, and white blood cell (WBC) and neutrophil count were
      significantly higher in patients with acute carditis compared with the controls
      (p < 0.001). NLR was found to have a significantly positive correlation with CRP
      (r = 0.177, p = 0.001), ESR (r = 0.81, p = 0.03) and WBC count ( r = 0.47, p =
      0.001). Moreover, we found a positive correlation between NLR and severity of
      valvular regurgitation (r = 0.34, p < 0.001), and a negative correlation between
      MPV and severity of valvular regurgitation ( r = -0.38, p < 0.05) in our
      patients. In multiple linear regression analysis, severe valvular regurgitation
      was associated with NLR (0.51; 95% CI: 0.32-0.68; p = 0.006) and MPV ( -0.78; 95%
      CI: -0.72 to -0.98; p = 0.008). CONCLUSIONS: NLR and MPV are novel inflammatory
      markers and simple, rapid and easily accessible prognostic parameters that can be
      associated with severity of valvular involvement in patients with ARC.

PMID- 30198548
TI  - Antibiotics for acute rhinosinusitis in adults.
AB  - BACKGROUND: Acute rhinosinusitis is an acute infection of the nasal passages and
      paranasal sinuses that lasts less than four weeks. Diagnosis of acute
      rhinosinusitis is generally based on clinical signs and symptoms in ambulatory
      care settings. Technical investigations are not routinely performed, nor are they
      recommended in most countries. Some trials show a trend in favour of antibiotics,
      but the balance of benefit versus harm is unclear.We merged two Cochrane Reviews
      for this update, which comprised different approaches with overlapping
      populations, resulting in different conclusions. For this review update, we
      maintained the distinction between populations diagnosed by clinical signs and
      symptoms, or imaging. OBJECTIVES: To assess the effects of antibiotics versus
      placebo or no treatment in adults with acute rhinosinusitis in ambulatory care
      settings. SEARCH METHODS: We searched CENTRAL (2017, Issue 12), which contains
      the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE
      (January 1950 to January 2018), Embase (January 1974 to January 2018), and two
      trials registers (January 2018). We also checked references from identified
      trials, systematic reviews, and relevant guidelines. SELECTION CRITERIA:
      Randomised controlled trials of antibiotics versus placebo or no treatment in
      people with rhinosinusitis-like signs or symptoms or sinusitis confirmed by
      imaging. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted
      data about cure and side effects and assessed the risk of bias. We contacted
      trial authors for additional information as required. MAIN RESULTS: We included
      15 trials involving 3057 participants. Of the 15 included trials, 10 appeared in
      our 2012 review, and five (631 participants) are legacy trials from merging two
      reviews. No new studies were included from searches for this update. Overall,
      risk of bias was low. Without antibiotics, 46% of participants with
      rhinosinusitis, whether or not confirmed by radiography, were cured after 1 week
      and 64% after 14 days. Antibiotics can shorten time to cure, but only 5 to 11
      more people per 100 will be cured faster if they receive antibiotics instead of
      placebo or no treatment: clinical diagnosis (odds ratio (OR) 1.25, 95% confidence
      interval (CI) 1.02 to 1.54; number needed to treat for an additional beneficial
      outcome (NNTB) 19, 95% CI 10 to 205; I2 = 0%; 8 trials; high-quality evidence)
      and diagnosis confirmed by radiography (OR 1.57, 95% CI 1.03 to 2.39; NNTB 10,
      95% CI 5 to 136; I2 = 0%; 3 trials; moderate-quality evidence). Cure rates with
      antibiotics were higher when a fluid level or total opacification in any sinus
      was found on computed tomography (OR 4.89, 95% CI 1.75 to 13.72; NNTB 4, 95% CI 2
      to 15; 1 trial; moderate-quality evidence). Purulent secretion resolved faster
      with antibiotics (OR 1.58, 95% CI 1.13 to 2.22; NNTB 10, 95% CI 6 to 35; I2 = 0%;
      3 trials; high-quality evidence). However, 13 more people experienced side
      effects with antibiotics compared to placebo or no treatment (OR 2.21, 95% CI
      1.74 to 2.82; number needed to treat for an additional harmful outcome (NNTH) 8,
      95% CI 6 to 12; I2 = 16%; 10 trials; high-quality evidence). Five fewer people
      per 100 will experience clinical failure if they receive antibiotics instead of
      placebo or no treatment (Peto OR 0.48, 95% CI 0.36 to 0.63; NNTH 19, 95% CI 15 to
      27; I2 = 21%; 12 trials; high-quality evidence). A disease-related complication
      (brain abscess) occurred in one participant (of 3057) one week after receiving
      open antibiotic therapy (clinical failure, control group). AUTHORS' CONCLUSIONS:
      The potential benefit of antibiotics to treat acute rhinosinusitis diagnosed
      either clinically (low risk of bias, high-quality evidence) or confirmed by
      imaging (low to unclear risk of bias, moderate-quality evidence) is marginal and
      needs to be seen in the context of the risk of adverse effects. Considering
      antibiotic resistance, and the very low incidence of serious complications, we
      conclude there is no place for antibiotics for people with uncomplicated acute
      rhinosinusitis. We could not draw conclusions about children, people with
      suppressed immune systems, and those with severe sinusitis, because these
      populations were not included in the available trials.

PMID- 30198549
TI  - Prognostic factors and primary treatment for Waldenstrom macroglobulinemia - a
      Swedish Lymphoma Registry study.
AB  - We present a nationwide prospective Swedish registry-based study of Waldenstrom
      macroglobulinaemia (WM), that focuses on incidence and survival in relation to
      clinical prognostic factors and primary systemic therapies. A total of 1511
      patients with WM and lymphoplasmocytic lymphoma (LPL) were registered in the
      Swedish Lymphoma Registry (SLR) between 1 January 2000 and 31 December 2014. The
      age-adjusted incidence of WM/LPL was 11.5 per million persons per year, three
      times higher than the reported incidence worldwide. Medical records were
      retrieved for 1135 patients (75%). A retrospective review showed that 981 (86.1%)
      of these patients fulfilled the World Health Organization diagnostic criteria for
      WM and these patients were analysed further. The overall survival (OS) improved
      between two periods - 2000-2006 and 2007-2014 - with a five-year OS of 61% and
      70%, respectively. Significant prognostic factors for OS, evaluated at the time
      of diagnosis, were age, elevated lactate dehydrogenase level and haemoglobin
      <=115 g/l for patients receiving therapy 0-3 months after diagnosis, and age,
      poor performance status, haemoglobin <=115 g/l, and female sex in "watch and
      wait" patients (multivariable analysis). The level of the IgM monoclonal
      immunoglobulin had no significant prognostic value. Rituximab included in first
      line therapy was associated with improved survival.

PMID- 30198550
TI  - Relationship between parent involvement and academic achievement through
      metacognitive strategies: A multiple multilevel mediation analysis.
AB  - BACKGROUND: Different studies reveal an association between parent involvement,
      metacognition, and academic achievement; however, the majority analyse the
      developmental process of acquisition in experimental or quasi-experimental
      designs with students enrolled in child education. Adolescence is an important
      stage in personal and academic development. Given the complexity of learning, and
      according to the metacognitive and affective model of self-regulated learning
      (Efklides, 2011, Educational Psychologist, 46, 6), different types of
      metacognitive processes are relevant for the optimal development of individuals
      in academic contexts. At the same time, individuals need stimuli from the
      environment, based on observation of their own and other's behaviour, as well as
      through communication and interaction with others. AIM: The present study
      examined the relations among parent involvement, metacognitive strategies, and
      academic achievement to investigate the mediational role of metacognition in the
      relation between parent involvement and academic achievement. SAMPLE: The
      participants were 1,398 high school students from Spain (47% female, M = 12. 5
      years). METHOD: Multiple multilevel mediation analyses with Monte Carlo
      confidence intervals were used for measuring within-subjects effects at the
      student level and between-subjects effects at the class level. Parent involvement
      (perception of support, organization, and interest in the educational process;
      expectations; school relationship; time of support with homework) and
      metacognition were measured by questionnaires, whereas academic achievement was
      assessed using the end-of-term grades obtained by students for nine subjects.
      RESULTS: First, there was a significant direct effect of most parent involvement
      constructs on the mediational and dependent variables at both the within and
      between levels. Expectations had the highest predictive power on academic
      achievement. On the other hand, metacognitive strategies were an important
      mediator for all parent involvement constructs at both levels of analysis.
      CONCLUSIONS: These results highlight the importance of metacognition during early
      adolescence and suggest that parent involvement is crucial for the future
      development of educational models.

PMID- 30198551
TI  - Lower prevalence of subsegmental pulmonary embolism after application of the
      YEARS diagnostic algorithm.
AB  - The rate of identified isolated subsegmental pulmonary embolism (ssPE) has
      doubled with advances in computed tomography pulmonary angiography (CTPA)
      technology, but its clinical relevance is debated. The YEARS diagnostic algorithm
      was shown to safely reduce the number of required CTPAs in the diagnostic
      management of PE. We hypothesized that the higher threshold for performing CTPA
      in YEARS was associated with a lower prevalence of ssPE compared to the
      conventional diagnostic algorithm. We compared 2291 consecutive patients with
      suspected PE managed according to YEARS to 3306 consecutive control patients
      managed according to the Wells score for the prevalence of isolated ssPE. In the
      YEARS cohort, 52% were managed without CTPA, 12% had pulmonary embolism (PE) of
      which 10% were isolated ssPE, and the 3-month diagnostic failure rate was 0.35%.
      In the control cohort, 32% were managed without CTPA, 20% had PE of which 16%
      were isolated ssPE, and the 3-month failure rate was 0.73%. The isolated ssPE
      prevalence was significantly lower in YEARS (absolute difference 6.2% (95%
      confidence interval [CI] 1.4-10), Odds Ratio 0.58 (95% CI 0.37-0.90). In
      conclusion, YEARS is associated with a lower prevalence of isolated ssPE, due to
      reduction in CTPAs by the higher D-dimer threshold. This was however not
      associated with a higher risk of recurrent VTE during follow-up.

PMID- 30198552
TI  - Diagnosis of pulmonary embolism: should we wait YEARS?

PMID- 30198553
TI  - Two types of serial dependence in visual working memory.
AB  - Stimulus representations in working memory depend on memory traces of past
      stimuli both from previous trials and from the current trial. However, it is
      unclear whether the same or different mechanisms underlie this serial dependence
      across and within trials. We directly contrasted estimates of bias for pairs of
      immediately successive stimuli across and within trials. In each trial,
      participants memorized two consecutive motion direction stimuli (S1 and S2) and
      after a short delay were cued to report one of them. We found serial dependence
      across trials: The current S1 was attracted towards the preceding S2 when the
      latter had been cued for report. In contrast, within the same trial S2 was
      repulsed from S1. In addition, repulsion within a trial occurred for a broader
      range of motion direction differences between stimuli than attraction across
      trials. A second experiment in which 25% of trials did not require a response
      demonstrated that across-trial attraction did not depend on whether the previous
      S2 actually had to be reported. Our findings provide evidence for two types of
      serial dependence operating across and within trials. They support the notion of
      different mechanisms integrating or segregating current from similar past memory
      contents depending on their task relevance.

PMID- 30198554
TI  - Clinical aspects of hereditary spastic paraplegia 76 and novel CAPN1 mutations.

PMID- 30198555
TI  - Mechanical incompatibility caused by modifications of multiple male genital
      structures using genomic introgression in Drosophila.
AB  - Mechanical incompatibility of male and female genitalia is common in animals with
      internal fertilization. However, our knowledge regarding the precise mechanisms
      is limited. One key question regards the susceptibility of the match between male
      and female genitalia to morphological modification. To address this issue, we
      generated six different second-chromosome introgression lines possessing
      partially Drosophila mauritiana-like genital morphology in multiple structures in
      D. simulans background. Three of the six introgression males showed elevated
      mobility at some stages during copulation with D. simulans females; this was
      assumed to be an indication of genital mismatch. Notably, one of the
      introgression males with D. mauritiana-like enlarged anal plates showed
      occasional leakage of adhesive ejaculate on the body surface when mated with pure
      D. simulans females, suggesting apparent structural incompatibility in genital
      coupling. These observations suggested that both sexual and natural selection
      shape the anal plate morphology, highlighting the role of this structure as an
      important component of mechanical isolation. Partial replacement (introgression)
      by a sibling species genome can induce perturbations in genital coupling
      mechanics, suggesting that genital compatibility can be susceptible to subtle
      genomic changes at the early stages of divergence in these species.

PMID- 30198556
TI  - Somatic modulation of ectopic action potential initiation in distal axons.

PMID- 30198557
TI  - Quantifying the relationship between optical anatomy and retinal physiological
      sensitivity: A comparative approach.
AB  - Light intensity varies 1 million-fold between night and day, driving the
      evolution of eye morphology and retinal physiology. Despite extensive research
      across taxa showing anatomical adaptations to light niches, surprisingly few
      empirical studies have quantified the relationship between such traits and the
      physiological sensitivity to light. In this study, we employ a comparative
      approach in frogs to determine the physiological sensitivity of eyes in two
      nocturnal (Rana pipiens, Hyla cinerea) and two diurnal species (Oophaga pumilio,
      Mantella viridis), examining whether differences in retinal thresholds can be
      explained by ocular and cellular anatomy. Scotopic electroretinogram (ERG)
      analysis of relative b-wave amplitude reveals 10- to 100-fold greater light
      sensitivity in nocturnal compared to diurnal frogs. Ocular and cellular optics
      (aperture, focal length, and rod outer segment dimensions) were assessed via the
      Land equation to quantify differences in optical sensitivity. Variance in retinal
      thresholds was overwhelmingly explained by Land equation solutions, which
      describe the optical sensitivity of single rods. Thus, at the b-wave, stimulus
      response thresholds may be unaffected by photoreceptor convergence (which create
      larger, combined collecting areas). Follow-up experiments were conducted using
      photopic ERGs, which reflect cone vision. Under these conditions, the relative
      difference in thresholds was reversed, such that diurnal species were more
      sensitive than nocturnal species. Thus, photopic data suggest that rod-specific
      adaptations, not ocular anatomy (e.g., aperture and focal distance), drive
      scotopic thresholds differences. To the best of our knowledge, these data provide
      the first quantified relationship between optical and physiological sensitivity
      in vertebrates active in different light regimes.

PMID- 30198558
TI  - Staqeya: the lone wolf at the edge of its ecological niche.

PMID- 30198559
TI  - Inter- and intra-specific differences in muscarinic acetylcholine receptor
      expression in the neural pathways for vocal learning in songbirds.
AB  - Acetylcholine receptors (AChRs) abound in the central nervous system of
      vertebrates. Muscarinic AChRs (mAChRs), a functional subclass of AChRs, mediate
      neuronal responses via intracellular signal transduction. They also play roles in
      sensorimotor coordination and motor skill learning by enhancing cortical
      plasticity. Learned birdsong is a complex motor skill acquired through
      sensorimotor coordination during a critical period. However, the functions of
      AChRs in the neural circuits for vocal learning and production remain largely
      unexplored. Here, we report the unique expression of mAChRs subunits (chrm2-5) in
      the song nuclei of zebra finches. The expression of excitatory subunits (chrm3
      and chrm5) was downregulated in the song nuclei compared with the surrounding
      brain regions. In contrast, the expression of inhibitory mAChRs (chrm2 and chrm4)
      was upregulated in the premotor song nucleus HVC relative to the surrounding
      nidopallium. Chrm4 showed developmentally different expression in HVC during the
      critical period. Compared with chrm4, individual differences in chrm2 expression
      emerged in HVC early in the critical period. These individual differences in
      chrm2 expression persisted despite testosterone administration or auditory
      deprivation, which altered the timing of song stabilization. Instead, the
      variability in chrm2 expression in HVC correlated with parental genetics. In
      addition, chrm2 expression in HVC exhibited species differences and individual
      variability among songbird species. These results suggest that mAChRs play an
      underappreciated role in the development of species and individual differences in
      song patterns by modulating the excitability of HVC neurons, providing a
      potential insight into the gating of auditory responses in HVC neurons.

PMID- 30198562
TI  - The Role of Parents in Emerging Adults' Psychological Well-Being: A Person
      Oriented Approach.
AB  - The purpose of this study was to gain an overview of Spanish emerging adults'
      family relationships and their link with psychological well-being and
      psychological distress. The sample comprised 1502 undergraduate students (903
      women and 599 men) aged between 18 and 29 (M = 20.32 and SD = 2.13), recruited
      from two universities in Spain. A cluster analysis identified three groups of
      families based on the centrality of five family variables: parental involvement,
      parental support for autonomy, parental warmth, behavioral control, and
      psychological control. The three groups or clusters were labeled high-quality
      family relationships (HQ), intermediate-quality family relationships (IQ), and
      low-quality family relationships (LQ). Women were overrepresented in the HQ
      cluster, whereas men were overrepresented in the IQ cluster. Moreover, emerging
      adults who perceived better family relationships (high levels of parental
      involvement, parental support for autonomy and parental warmth, and low levels of
      behavioral and psychological control) were found to have a higher level of
      psychological adjustment. Thus, our results indicate that family plays a key role
      in the psychological well-being of emerging adults. The discussion focuses on the
      implications of this finding for the parent-child relationship, and explores how
      it extends our knowledge about family relationships during emerging adulthood.

PMID- 30198561
TI  - Tannins from Terminalia chebula fruits attenuates GABA antagonist-induced anxiety
      like behaviour via modulation of neurotransmitters.
AB  - OBJECTIVES: This article investigates the anxiolytic activity of Terminalia
      chebula tannin-rich extract against picrotoxin (PTX; GABA antagonist)-induced
      anxiety in mice model. METHODS: Anxiolytic activity was studied by elevated plus
      maze (EPM), open field test (OFT), light/dark box test (LDT) and Vogel's conflict
      test (VCT). Electroencephalogram (EEG) was performed to know the changes in brain
      activity instigated by GABA antagonist. 5-hydroxytryptamine (5-HT), dopamine and
      norepinephrine levels in brain tissues were estimated by HPLC. The mRNA (CREB,
      BDNF, GABA, and 5-HT1A ) and protein expression (CREB, p-CREB, BDNF, ERK 1/2, p
      ERK 1/2, GABAA Ralpha1, 5-HT1A and GAPDH) levels in brain tissue were determined
      by RT-PCR and Western blot analysis, respectively. KEY FINDINGS: Terminalia
      chebula tannin-rich extract (TCHE) supplementation increased locomotion in mice
      towards open arm (EPM), time spent in illuminated area (LDT), rearing frequency
      (OFT) and number of shocks (VCT) compared to PTX (P < 0.05). Furthermore, TCHE
      down-regulated serum cortisol levels and showed increased levels of 5-HT, DA and
      NE. Gene expressions such as BDNF, CREB, GABAA and 5-HT1A were up-regulated by
      TCHE treatment compared to PTX. CONCLUSIONS: Terminalia chebula tannin-rich
      extract showed significant anxiolytic activity against picrotoxin and could be
      used as natural therapy in neurodegenerative disorders.

PMID- 30198560
TI  - Drug Shortage Impacts Patient Receipt of Induction Treatment.
AB  - OBJECTIVE: Examine the impact of the 2011 shortage of the drug cytarabine on
      patient receipt and timeliness of induction treatment for Acute Myeloid Leukemia
      (AML). STUDY DESIGN: A retrospective cohort was utilized to examine odds of
      receipt of inpatient induction chemotherapy and time to first dose across major
      (N = 105) and moderate (N = 316) shortage time periods as compared to a
      nonshortage baseline (N = 1,147). DATA COLLECTION/EXTRACTION METHODS: De
      identified patient data from 2008 to 2011 Surveillance, Epidemiology, and End
      Results (SEER) were linked to 2007-2013 Medicare claims and 2007-2013 Hospital
      Characteristics. PRINCIPAL FINDINGS: Compared to prior nonshortage time period,
      patients diagnosed during a major drug shortage were 47 percent less likely (p <
      .05) to receive inpatient chemotherapy within 14 days of diagnosis. Patients who
      were younger, had a lower Charlson Comorbidity score, and for whom AML was a
      first primary cancer were prioritized across all periods. CONCLUSIONS: Period of
      major shortage of a generic oncolytic, without an equivalent therapeutic
      substitute, reduced timely receipt of induction chemotherapy treatment. More
      favorable economic and regulatory policies for generic drug suppliers might
      result in greater availability of essential, older generic drug products that
      face prolonged or chronic shortage.

PMID- 30198564
TI  - Alterations in synaptic density and myelination in response to exposure to high
      energy charged particles.
AB  - High-energy charged particles are considered particularly hazardous components of
      the space radiation environment. Such particles include fully ionized energetic
      nuclei of helium, silicon, and oxygen, among others. Exposure to charged
      particles causes reactive oxygen species production, which has been shown to
      result in neuronal dysfunction and myelin degeneration. Here we demonstrate that
      mice exposed to high-energy charged particles exhibited alterations in dendritic
      spine density in the hippocampus, with a significant decrease of thin spines in
      mice exposed to helium, oxygen, and silicon, compared to sham-irradiated
      controls. Electron microscopy confirmed these findings and revealed a significant
      decrease in overall synapse density and in nonperforated synapse density, with
      helium and silicon exhibiting more detrimental effects than oxygen. Degeneration
      of myelin was also evident in exposed mice with significant changes in the
      percentage of myelinated axons and g-ratios. Our data demonstrate that exposure
      to all types of high-energy charged particles have a detrimental effect, with
      helium and silicon having more synaptotoxic effects than oxygen. These results
      have important implications for the integrity of the central nervous system and
      the cognitive health of astronauts after prolonged periods of space exploration.

PMID- 30198565
TI  - Plasma metabolomics analysis in sickle cell disease patients with albuminuria -
      an exploratory study.

PMID- 30198566
TI  - Fitting psychotherapy to patient coping style: A meta-analysis.
AB  - Over the course of 60 years of research, several personality traits have emerged
      as potential predictors of differential change in psychotherapy. Among them is
      the patient's coping style (CS), commonly distinguished between those who deal
      with change by looking inwardly (internalization) and those who deal with it
      outwardly (externalization). This study provides definitions of CSs, clinical
      examples, and frequent measures. We update a 2011 meta-analytic review that
      revealed a consistent interaction between CSs and treatment focus-symptom focus
      versus insight focus. The current meta-analysis of 18 studies revealed a medium
      to large effect (d = 0.60) and suggested that a symptom focus proves more
      effective for externalizing patient whereas an insight focus is generally more
      effective for internalizers. The article concludes with limitations of the
      research, diversity considerations, and therapeutic practices based on the meta
      analytic results.

PMID- 30198563
TI  - The two FIGO systems for normal and abnormal uterine bleeding symptoms and
      classification of causes of abnormal uterine bleeding in the reproductive years:
      2018 revisions.
AB  - BACKGROUND: The International Federation of Gynecology and Obstetrics (FIGO)
      systems for nomenclature of symptoms of normal and abnormal uterine bleeding
      (AUB) in the reproductive years (FIGO AUB System 1) and for classification of
      causes of AUB (FIGO AUB System 2; PALM-COEIN) were first published together in
      2011. The purpose was to harmonize the definitions of normal and abnormal
      bleeding symptoms and to classify and subclassify underlying potential causes of
      AUB in the reproductive years to facilitate research, education, and clinical
      care. The systems were designed to be flexible and to be periodically reviewed
      and modified as appropriate. OBJECTIVES: To review, clarify, and, where
      appropriate, revise the previously published systems. METHODOLOGY AND OUTCOME: To
      a large extent, the process has been an iterative one involving the FIGO
      Menstrual Disorders Committee, as well as a number of invited contributions from
      epidemiologists, gynecologists, and other experts in the field from around the
      world between 2012 and 2017. Face-to-face meetings have been held in Rome,
      Vancouver, and Singapore, and have been augmented by a number of teleconferences
      and other communications designed to evaluate various aspects of the systems.
      Where substantial change was considered, anonymous voting, in some instances
      using a modified RAND Delphi technique, was utilized.

PMID- 30198567
TI  - Investigation of potent anticarcinogenic activity of 1, 3-diarylpyrazole
      acrylamide derivatives in vitro.
AB  - OBJECTIVES: Pyrazole derivatives are pharmacologically powerful agents pointing
      at new horizons in the development of anticancer therapies. In this study,
      anticarcinogenic potential of a series of pyrazole-acrylamide derivatives has
      been investigated in mesothelial, malignant mesothelioma and lung cancer cell
      lines. METHODS: The effect of compounds on the viability of cells and the
      distribution of cell cycle were examined through MTS assay and PI staining,
      respectively. Apoptosis was evaluated via caspase-3 enzymatic assay and AO/EB
      staining. Proteins involved in proliferation, survival and apoptosis were
      analysed by immunoblotting. KEY FINDINGS: Twelve compounds of 21 (4a-4v) reduced
      the viability of cells but, only the subset of five (4f, 4i, 4j, 4k and 4v)
      induced the caspase-3 activity. Among five, only one compound (4k) significantly
      suppressed phosphorylation and expression of ERK1/2 and AKT proteins in 24 h.
      Exposing cancer cells to successive concentrations of 4k gave rise to dose- and
      time-dependent G2/M phase arrest and apoptosis. CONCLUSIONS: 4k has revealed its
      potent antiproliferative activity by decreasing viability and inhibiting
      proliferation and survival signals of cancer cells. Moreover, 4k has exposed
      cytostatic and apoptotic effect especially, on cancer cells. Therefore, it may be
      necessary to examine the biological actions of 4k in vivo as well.

PMID- 30198568
TI  - CD13 expression in B cell malignancies is a hallmark of plasmacytic
      differentiation.
AB  - The diagnosis of Waldenstrom Macroglobulinaemia (WM)/lymphoplasmacytic lymphoma
      (LPL) remains one of exclusion because other B-cell lymphoproliferative disorders
      (B-LPD), such as marginal zone lymphoma (MZL), can fulfil similar criteria,
      including MYD88 L265P mutation. It has been suggested that expression of the
      myeloid marker CD13 (also termed ANPEP) is more frequent in LPL than in other B
      LPD and has also been described on normal and malignant plasma cells. Here, CD13
      expression was tested in a cohort of 1037 B-LPD patients from 3 centres by flow
      cytometry. The percentage of CD13-expressing cells was found to be variable among
      B-LPD but significantly higher in WM/LPL (median 31% vs. 0% in non-WM/LPL, P <
      0.001). In multivariate linear regression, CD13 expression remained significantly
      associated with a diagnosis of WM/LPL (P < 0.001). A cut-off value of 2% of CD19+
      cells co-expressing CD13 yielded the best diagnostic performance for WM/LPL
      assertion. This was further improved by association with the presence or absence
      of IgM paraprotein. Finally, given that previously published transcriptomic data
      revealed no difference in CD13 (also termed ANPEP) mRNA between normal and
      pathological B-cells, the hypothesis of some post-transcriptional regulation must
      be favoured. These results suggest that testing for CD13 expression in routine
      flow cytometry panels could help to discriminate WM/LPL from other B-LPD.

PMID- 30198569
TI  - The miR-17~92 cluster activates mTORC1 in mantle cell lymphoma by targeting
      multiple regulators in the STK11/AMPK/TSC/mTOR pathway.

PMID- 30198570
TI  - Whole exome sequencing discloses heterozygous variants in the DNAJC21 and EFL1
      genes but not in SRP54 in 6 out of 16 patients with Shwachman-Diamond Syndrome
      carrying biallelic SBDS mutations.

PMID- 30198571
TI  - Pulmonary toxicity in paediatric patients with relapsed or refractory Hodgkin
      lymphoma receiving brentuximab vedotin.
AB  - Brentuximab vedotin (Bv) is becoming increasingly important in the treatment of
      Hodgkin lymphoma (HL), with improved outcomes and an overall favourable toxicity
      profile. However, Bv is associated with severe pulmonary toxicity when combined
      with bleomycin, suggesting that additive toxicity may be an important
      consideration. Furthermore, little has been published on tolerability in
      paediatric patients. We retrospectively evaluated the occurrence of pulmonary
      toxicity of Bv in 19 paediatric and young adult patients with relapsed or
      refractory HL. Patient characteristics, baseline health status, treatment
      regimens including cumulative doses of Bv, bleomycin, gemcitabine, radiation and
      carmustine, and the occurrence of pulmonary toxicity were collected. Seven
      (36.8%) of the 19 patients were treated with Bv. The odds of pulmonary toxicity
      were 4.0-fold higher (95% confidence interval 0.55-29.18) in patients exposed to
      Bv compared to unexposed patients in univariate analysis (P = 0.17). Similar
      results were found in multivariable analysis. Pulmonary toxicity occurred
      frequently in our cohort and was more common in patients who received Bv than in
      patients who did not receive Bv, although this was not statistically significant.
      Because patients with HL are exposed to a myriad of therapies with potential for
      pulmonary toxicity, continuing to evaluate the risk associated with Bv is
      critical.

PMID- 30198572
TI  - Novel mutations in SPTA1 and SPTB identified by whole exome sequencing in eight
      Thai families with hereditary pyropoikilocytosis presenting with severe fetal and
      neonatal anaemia.

PMID- 30198573
TI  - Negative relationships between species richness and temporal variability are
      common but weak in natural systems.
AB  - Effects of species diversity on population and community stability (or more
      precisely, the effects of species richness on temporal variability) have been
      studied for several decades, but there have been no large-scale tests in natural
      communities of predictions from theory. We used 91 data sets including plants,
      fish, small mammals, zooplankton, birds, and insects, to examine the relationship
      between species richness and temporal variability in populations and communities.
      Seventy-eight of 91 data sets showed a negative relationship between species
      richness and population variability; 46 of these relationships were statistically
      significant. Only five of the 13 positive richness-population variability
      relationships were statistically significant. Similarly, 51 of 91 data sets
      showed a negative relationship between species richness and community
      variability; of these, 26 were statistically significant. Seven of the 40
      positive richness-community-variability relationships were statistically
      significant. We were able to test transferability (i.e., the predictive ability
      of models for sites that are spatially distinct from sites that were used to
      build the models) for 69 of 91 data sets; 35 and 31 data sets were transferable
      at the population and community levels, respectively. Only four were positive at
      the population level, and two at the community level. We conclude that there is
      compelling evidence of a negative relationship between species richness and
      temporal variability for about one-half of the ecological communities we
      examined. However, species richness explained relatively little of the
      variability in population or community abundances and resulted in small
      improvements in predictive ability.

PMID- 30198574
TI  - An integrative salivary approach regarding palate cleansers in wine tasting.
AB  - : Wine sensory sessions normally involve the tasting of several samples, to
      remove food residues from the mouth the use of palate cleansers (PC) is needed.
      Until now, there is no agreement on the best PC to use during wine tasting
      sessions. The aim of this work is to study the relationship between the
      components retained in saliva after wine tasting and the remnant sensory feeling
      (astringency, alcohol, and acidity). For that, different common PC (water,
      carbonated water, and milk) were tested and saliva samples (expectorated and
      scraped) from nine trained panelists were collected after wine with and without
      PC trials. Results showed that after palate cleansing and not cleansing,
      astringency, alcoholic and acidity perception were influenced by time, PC and
      panelist. Astringency perception showed the greatest intensity in comparison to
      alcoholic and acidity. Milk was the only PC which reduced quantifiable
      polyphenols in expectorated saliva, as well as reducing astringency feelings.
      Although compositions of expectorated and scraped saliva correlated between them,
      polyphenols accumulated in the expectorated saliva significantly more. Retained
      polyphenols were correlated with astringency perception, but no correlation was
      found with salivary proteins. These findings assessed the astringency build-up
      effect during wine tasting due to polyphenols accumulation in saliva, remarking
      the importance of an adequate PC selection. All things considered, the present
      work confirmed the relationship between after-swallow mouthfeel perception and
      mouth residues instrumentally quantified. Also, milk has proven to be the most
      effective of the three PC. PRACTICAL APPLICATIONS: During tasting the
      accumulation of residues from previous wine samples tasted, could mislead the
      judgment of wine sensory qualities by oenologists. Therefore, between tasting
      samples it is highly important to choose the right PC. However, until now the
      selection of PC remains empirical, therefore in this work, we proposed to study
      the residues in saliva by using different PC and quantifying instrumentally, the
      wine residues. The methodology selected to quantify the wines residues in saliva
      was quick and easy to use. Furthermore, instrumental results were related with
      the sensory feeling of mouth cleanliness without considering individual panel
      member's preferences of PC. In this study, to remove astringency feeling, milk
      was shown to be the best cleanser in comparison with water, carbonated water or
      nothing, but oenologist/winemakers could use this instrumental methodology in
      saliva to select which one is the best among their current PC used.

PMID- 30198575
TI  - How are macronutrient intake, BMI, ethnicity, age, and gender related to the
      composition of unstimulated saliva? A case study.
AB  - : This study investigated how macronutrient intake, BMI, ethnicity, age, and
      gender are related to the composition of unstimulated saliva. First, two groups
      of Caucasian, Dutch subjects varying in daily intake of carbohydrate, fat, and
      protein were selected. The daily intake of macronutrients differed by two- to
      threefold between the low (n = 14) and high (n = 16) macronutrient intake groups.
      The same subjects were divided into two groups based on BMI: normal weight (n =
      14, 22.5 +/- 2.0 kg/m2 ) and overweight (n = 16, 28.1 +/- 3.4 kg/m2 ). Second,
      one group of Caucasian, Dutch (n = 15) and one group of Asian, Chinese (n = 15)
      subjects were selected. Unstimulated saliva was collected from all groups.
      Protein concentration, amylolytic activity, lipolytic activity, and saliva flow
      rate were determined. None of the salivary parameters varied according to
      macronutrient intake and BMI. An effect of ethnicity on protein concentration was
      observed (p < .01; eta2 = 0.142), with Asians having a 45% higher protein
      concentration in unstimulated saliva than Caucasians. Age had a significant
      effect on all salivary parameters. Protein concentration (p < .01; eta2 = 0.256),
      amylolytic activity (p < .01; eta2 = 0.234), and lipolytic activity (p < .05;
      eta2 = 0.207) increased with age, while saliva flow rate decreased (p < .01; eta2
      = 0.262). Gender had a significant effect on saliva flow rate (p < .01; eta2 =
      0.130), with male subjects having a 32% higher flow rate than females. Age was
      the factor that had the greatest impact on the characteristics of unstimulated
      saliva. As the modulation of saliva composition according to diet has been
      reported previously, the extent to which macronutrient intake can affect saliva
      composition needs to be further investigated. PRACTICAL APPLICATIONS: Saliva
      plays an important role in food oral processing. From the breakdown of food
      structures to the binding of flavor compounds and the formation of a swallowable
      bolus, saliva is essential for the perception and appreciation of foods.
      Identifying the factors that affect saliva composition is, therefore, necessary
      to understand the differences in eating behavior, food perception, and preference
      across different consumer groups. This article aims to highlight the importance
      of considering saliva variability when designing food products that meet the
      needs of specific consumer groups.

PMID- 30198576
TI  - Origins of material loss in highly worn acetabular cups of metal-on-metal total
      hip replacements.
AB  - Excessive wear has been one of the major failure modes of metal-on-metal hip
      implants. From a collection of 541 retrieved ASR metal-on-metal implants, we
      selected those head-cup pairs with combined wear >100 mm3 , (N = 42) to assess
      the distributions of wear volume on cups, and non-conformance in the worn areas
      at the head-cup interfaces. All 42 had severe cup edge wear (average maximum wear
      depth 500 MUm). On average, 58% of wear volume of cups occurred at the edge
      areas, whereas 42% occurred well inside the socket, indicating that substantial
      wear volume of cups was generated well inside the socket. Particularly, in eight
      cups, more than half of the wear volume occurred well inside the socket. The head
      cup conformance in the worn areas was deteriorated. On average, in worn areas,
      head-cup clearance was approximately eight times greater than in unworn areas,
      and the sphericity of heads and cups was approximately 36 times and 84 times
      higher, respectively, than in unworn areas. The radius of curvature of the worn
      surfaces of heads and cups varied widely, with an average variation of 3 mm (0.6
      7 mm) and 11 mm (2-47 mm) for heads and cups, respectively. The severely
      deteriorated conformance at the edge areas and the areas well inside the socket,
      due to edge contact, could be the major factor for excessive wear of these 42
      pairs. (c) 2018 Orthopaedic Research Society. Published by Wiley Periodicals,
      Inc. J Orthop Res.

PMID- 30198577
TI  - Technical efficiency of Portuguese public hospitals: A comparative analysis
      across the five regions of Portugal.
AB  - The present study aims to analyse the efficiency scores of hospital units, with
      reference to the five Portuguese health administrative regions (North, Centre,
      Lisbon and Tagus Valley, Alentejo, and Algarve). This paper contextualizes the
      process of decentralization of health in Portugal (started 1993) as well as the
      hospitals' corporatization and merging reforms (started 2002). These reforms
      aimed to meet health care needs by optimizing costs, improving efficiency, and
      broadening both access and quality in health services. Data envelopment analysis
      was used to quantify and compare the efficiencies of 27 hospitals heterogeneously
      distributed by five administrative regions. The results show a large average
      performance across the country. However, there are regions with scores larger
      than the national average and others with inferior results. This interregional
      diversity points towards disparities that deserve special attention from the
      policymakers and hospital managers.

PMID- 30198578
TI  - Hydrolysis Activity of Pyloric Cecal Enterocytes of Brown Trout (Salmo trutta)
      toward Monoacylglycerol and Lysophosphatidylcholine.
AB  - Some lipid digestion pathways in fish deviate from those in mammals, and many
      differences may also be species dependent. This report describes a pathway for
      monoacylglycerol (MAG) and lysophospholipid absorption by intestinal enterocytes
      in brown trout that may be of significance in salmonids. When culturing primary
      cells in a medium containing 1- and 2-MAG, we observed a massive hydrolysis of
      unesterified fatty acids. The hydrolysis activity was retained in the medium even
      after the removal of the cells. To further characterize these activities, both
      extracellular and isolated membrane proteins were tested for lipase activity
      toward triacylglycerol (TAG), diacylglycerol (DAG), MAG, phosphatidylcholine
      (PtdCho), and lysoPtdCho. In both cases, the main hydrolyzing activity was toward
      MAG followed by lysoPtdCho with very little activity toward DAG, TAG, or PtdCho.
      The extracellular and membrane proteins were partially purified by fast protein
      liquid chromatography and identified by proteomics (liquid chromatography-tandem
      mass spectrometry) focusing on lipase/hydrolase enzymes. In the membrane protein
      fraction, the data suggested that MAG was produced as an intermediate in the
      hydrolysis of lysoPtdCho by either lysophospholipase C or lysophospholipase D
      activity. Both abhydrolase-domain-containing protein 6 and abhydrolase-domain
      containing protein 12 were identified in the membrane protein and they could be
      responsible for the hydrolysis of MAG. In the culture medium, low-peptide matches
      were found for ABHD6 and phospholipases and further studies are needed. In
      summary, trout enterocytes are capable of hydrolyzing MAG and lysoPtdCho. The
      enzymes are both extracellular and membrane bound. The pathways may be of
      significance during lipid absorption in fish lacking a 1,3 specific pancreatic
      lipase.

PMID- 30198580
TI  - Screening for peripheral artery disease in people with diabetes.
AB  - We read with interest the recent article by Vriens et al. published in Diabetic
      Medicine [1]. The authors question the screening tools used to test for the
      presence of peripheral artery disease in people with diabetic foot ulcers. This
      is important because the complications of diabetes limit all commonly used, non
      invasive, bedside tests for peripheral artery disease. The utility of these tests
      in consecutive people presenting with ulceration, with and without infection,
      provides important information to guide clinical practice in a clinically
      relevant environment. This article is protected by copyright. All rights
      reserved.

PMID- 30198579
TI  - Study of the Involvement of Phosphatidic Acid Formation in the Expression of
      Wound-Responsive Genes in Cotton.
AB  - Plants use phospholipase D (PLD, EC 3.1.4.4)/phosphatidic acid (PtdOH) for the
      transduction of environmental signals including those coming from wounding. Based
      on our previous findings suggesting that wound-induced PLDalpha-derived PtdOH can
      act as a local signaling molecule in cotton (Gossypium hirsutum), we show that
      wounding immediately increases local NADPH oxidase (NADPHox) and cellulose
      synthase A (CeSA) gene expression. After developing a novel fluorimetric assay
      for the investigation of n-butanol inhibitory effect on PLD activity, we show
      that only NADPHox gene upregulation is reduced when n-butanol is applied prior to
      wounding. This suggests that NADPHox is a possible downstream target of PLD
      function, while a different CeSA-involving response system may exist in cotton.
      Overall, this study provides new knowledge on signal-transduction mechanisms
      following wounding of cotton leaves.

PMID- 30198581
TI  - Six Degrees of Separation: A Journey through Joint and Personal Connections.
AB  - My research on intraneural ganglion cysts has led me on a journey through history
      to discover a Six Degrees of Separation network, linking my interest in joint
      connections (of nerve) with personal interconnections. This research took me on
      an exciting personal journey through the history of neurology, anatomy, and hand
      and peripheral nerve surgery in Paris, France and New York City. Following famous
      footsteps like breadcrumbs, my Six Degrees of Separation to Duchenne de Boulogne
      and Edme Francois Chauvot de Beauchene (Beauchene fils) could be traced through
      personal connections with leaders including Baron Guillaume Dupuytren, Emanuel
      Kaplan, J. William Littler, Arthur J. and Hannah Barsky, and my father, Morton
      Spinner. I hope that this personal story will serve as a source of inspiration
      for both young and experienced physicians, who may read it with great interest
      and reflect on their own connections to people and leaders in their fields. This
      article is protected by copyright. All rights reserved.

PMID- 30198582
TI  - Predictors of treatment success in children with difficult to treat atopic
      dermatitis using a personalized integrative multidisciplinary (PIM) treatment
      programme.
AB  - BACKGROUND: A 6-week personalized integrative multidisciplinary treatment
      programme (PIM) was developed for children with difficult to treat AD who
      appeared unresponsive to treatment according to current guidelines. OBJECTIVE:
      The aim of the present study was to identify clinical and psychosocial
      characteristics that predict long-term treatment success after PIM. METHODS:
      Treatment was considered successful when there was a 75% reduction on the Self
      Administered Eczema Area and Severity Index and/or little impact of AD on daily
      life, measured with the Children's Dermatology Life Quality Index (score <= 6), 6
      months after the end of PIM. PIM is a personalized, integrative,
      multidisciplinary treatment programme with clearly defined goals and strategies,
      addressing atopic, paediatric, mental health comorbidities and general well
      being, for children and adolescents aged 8- to 18 years. Multivariate logistic
      regression models were constructed using a backward selection procedure.
      Questionnaires were used to assess psychosocial characteristics; clinical data
      was extracted from medical records. RESULTS: In total, 79 children/adolescents
      with difficult to treat AD completed PIM and long-term treatment results were
      available for 74 children/adolescents. The majority (77%) of children/adolescents
      demonstrated long-term treatment success with PIM. Predictors of long-term
      treatment success (adjusted ORs) included maternal disease acceptance OR (95% CI)
      1.84 (1.15-2.94). A group (23%) of mostly females OR (95% CI) 0.10 (0.02-0.54)
      with multiple somatic complaints OR (95% CI) 0.88(0.80-0.97), from families where
      the mother has anxiety for the use of topical corticosteroids OR (95% CI)
      0.62(0.40-0.94), is less likely to obtain long-term treatment success.
      CONCLUSION: Most children and adolescents with difficult to treat AD, seemingly
      unresponsive to conventional treatment according to current guidelines, are able
      to improve with PIM. Psychosocial and family but not clinical variables,
      predicted long-term treatment success after participating in PIM.

PMID- 30198583
TI  - Prevalence of and risk factors for dermatoporosis: a prospective observational
      study of dermatology outpatients in a Finnish tertiary care hospital.
AB  - BACKGROUND: Dermatoporosis describes the cutaneous signs and complications
      related to chronic cutaneous fragility related to ageing, chronic sun exposure
      and long-term use of topical and systemic corticosteroids. Chronic renal failure
      may be an additional cofactor. The prevalence of dermatoporosis is estimated
      around 32-37% in France among the elderly. OBJECTIVE: We evaluated the prevalence
      of dermatoporosis and its risk factors in outpatients who attended a consultation
      in the department of dermatology of Helsinki University Central Hospital.
      METHODS: A prospective observational study of 176 consecutive outpatients aged 60
      years and older, who attended a consultation in the department of dermatology of
      Helsinki University Central Hospital. Data collection included age, gender,
      reason for consultation, local or systemic corticosteroid therapy, antiplatelet
      drugs and anticoagulant therapy, diabetes and chronic kidney failure (glomerular
      filtration rate < 60 mL/min/m2 ). The presence of dermatoporosis, location on the
      body and staging were collected. RESULTS: 30.7% presented dermatoporosis. Lesions
      were mainly located on the upper limbs (94%), and stage I was the most frequent
      (75.9% of the cases). Multivariate analysis revealed that dermatoporosis was
      significantly associated with ultrapotent topical corticosteroids (odds ratio
      (OR) 5.34, 95% CI 1.85-15.43, P = 0.002), oral corticosteroids (OR 3.22, 95% CI
      1.18-8.80, P = 0.022), concomitant corticosteroid therapy, anticoagulant and
      chronic renal failure (OR 4.02, 95% CI 1.34-12.01, P = 0.013) and age (OR 1.05,
      95% CI 1.01-1.10, P = 0.016). Patients with bullous pemphigoid were those with
      the highest prevalence of dermatoporosis in our cohort (64%). CONCLUSION:
      Acknowledging the selection bias in our study, the prevalence of dermatoporosis
      in a dermatology consultation in Finland seems as frequent as in France. These
      results prompt us to weigh the indications of long-term corticosteroids use in
      frail elderly patients.

PMID- 30198584
TI  - Decreased photosensitivity to UVA on vemurafenib combined with cobimetinib.

PMID- 30198586
TI  - An international comparison of Google searches for sunscreen, sunburn, skin
      cancer, and melanoma: Current trends and public health implications.
AB  - BACKGROUND: Google Trends(r) (GT) offers insight into public interests and
      behaviors and holds potential for guiding public health campaigns. OBJECTIVES:
      This study explored international trends in English-speaking countries (United
      States, United Kingdom, Canada, Australia, New Zealand) in searches for
      sunscreen, sunburn, skin cancer, and melanoma to better guide skin cancer
      prevention campaigns. METHODS: Google Trends(r) was queried for search terms from
      January 1, 2004 to December 31, 2017. Respective national databases were queried
      for melanoma outcome data from 2004 to 2014 and compared with time-matched search
      data. Correlations between search terms, time, and melanoma outcomes were
      assessed for each country. Quantitative analyses were performed to evaluate
      differences in search volumes between countries with varying melanoma incidence.
      RESULTS: In all countries, the strongest intra-term correlation was between
      sunscreen and sunburn. Searches for sunscreen and sunburn are increasing for all
      countries. For all countries except the United Kingdom and New Zealand, searches
      for skin cancer and melanoma are decreasing for one or both terms. Correlations
      between search terms and melanoma outcomes were variable and specific to each
      country. Quantitative analysis revealed that countries with higher melanoma
      incidence had higher search volumes for all terms. Search volumes were especially
      high for skin cancer and melanoma in Australia compared with other countries.
      Comparisons between moderate melanoma incidence countries were less clear.
      CONCLUSIONS: Online skin cancer prevention campaigns should focus on the search
      terms sunburn and sunscreen, especially given the declining interest between 2004
      and 2016 in the terms skin cancer and melanoma seen in multiple countries. Search
      term interests varied with melanoma outcomes and between countries, suggesting
      the importance of customizing approaches based on local population interests and
      geographic areas.

PMID- 30198585
TI  - Skin cancer projections and cost savings 2014-2045 of improvements to the Danish
      sunbed legislation of 2014.
AB  - BACKGROUND: Sunbed use increases the risk of skin cancer. The Danish sunbed
      legislation (2014) did not include an age limit. AIM: To model skin cancer
      incidences and saved costs from potential effects of structural interventions on
      prevalence of sunbed use. MATERIALS AND METHODS: Survey data from 2015 were
      collected for 3999 Danes, representative for the Danish population in regards to
      age, gender and region. Skin cancer incidences were modelled in the Prevent
      program, using population projections, historic cancer incidence, sunbed use
      exposure and relative risk of sunbed use on melanoma. RESULTS: If structural
      interventions like an age limit of 18 years for sunbed use or complete ban had
      been included in the Danish sunbed legislation in 2014, it would have reduced the
      annual number of skin cancer cases with 455 or 4177, respectively, while for the
      entire period, 2014-2045 the total reductions would be 3730 or 81 887 fewer
      cases, respectively. The cost savings from an age limit or ban, respectively, are
      9 and 129 millions ? during 2014-2045. CONCLUSION: Legislative restrictive
      measures which could reduce the sunbed use exists. Danish politicians have the
      opportunity, supported by the population, to reduce the skin cancer incidence and
      thereby to reduce the future costs of skin cancer.

PMID- 30198587
TI  - The potential role of antioxidants in mitigating skin hyperpigmentation resulting
      from ultraviolet and visible light-induced oxidative stress.
AB  - Oxidative stress is an integral element that influences a variety of biochemical
      reactions throughout the body and is known to play a notable role in
      melanogenesis. Exogenous triggers of oxidative stress, such as ultraviolet
      radiation (UVR) and visible light (VL), lead to pigment formation through
      somewhat different pathways, but both share a common endpoint-the potential to
      generate cosmetically undesirable hyperpigmentation. Though organic and inorganic
      sunscreens are available to protect against the UVR portion of the
      electromagnetic spectrum, coverage is lacking to protect against the VL spectrum.
      In this manuscript, we review the phases of tanning, pathways of melanogenesis
      triggered by UVR and VL, and the associated impact of oxidative stress. We also
      discuss the known intrinsic mechanisms and paracrine regulation of melanocytes
      that influence their response to UVR. Understanding these mechanisms and their
      role in UVR-induced hyperpigmentation should potentially lead to identification
      of useful targets that can be coupled with antioxidant therapy to alleviate this
      effect.

PMID- 30198588
TI  - Long-term safety profile of ixekizumab in patients with moderate-to-severe plaque
      psoriasis: an integrated analysis from 11 clinical trials.
AB  - BACKGROUND: Psoriasis in many patients is a chronic and recalcitrant disease that
      requires long-term treatment, reinforcing the importance of long-term safety
      data. Ixekizumab, a high-affinity monoclonal antibody that selectively targets
      interleukin (IL)-17A, is approved for treating patients with moderate-to-severe
      plaque psoriasis. OBJECTIVE: To determine long-term safety of ixekizumab in
      psoriasis. METHODS: Integrated safety data are presented from 12-week induction
      period, 12-60-week maintenance period, and from all ixekizumab-treated patients
      from 11 clinical studies. Exposure-adjusted incidence rates (IRs) per 100 patient
      years are reported. RESULTS: Overall, 5689 patients accounted for 12 061.5
      patient-years of ixekizumab exposure from 11 studies. Over 156 weeks, a total of
      83.9% (n = 4775) of patients reported treatment-emergent adverse events (AEs).
      Most opportunistic infections (IR [95% confidence interval; CI] 1.8 [1.6, 2.1])
      reported were mucocutaneous candidiasis. The IR (95% CI) for oral Candida
      infection was 0.9 (0.8, 1.1). There was no trend of increase in IR of AEs of
      special interest. Serious AEs were reported in 11.8% of patients; death occurred
      in 0.4% (n = 23) of patients. CONCLUSION: The 3-year, long-term maintenance
      treatment with ixekizumab did not show any new safety signals in patients with
      moderate-to-severe plaque psoriasis.

PMID- 30198589
TI  - Diagnostic accuracy of a new ex vivo confocal laser scanning microscope compared
      to H&E-stained paraffin slides for micrographic surgery of basal cell carcinoma.
AB  - BACKGROUND: For safe excision of malignant skin tumours, complete negative
      surgical margins are mandatory. The gold standard for analysis is frozen sections
      or paraffin-embedded haematoxylin and eosin (H&E)-stained slides. The production
      of H&E-stained slides is time-consuming (>20 h) while wounds remain unclosed. An
      upcoming method is confocal laser scanning microscopy (CLSM), a technique that
      scans unfixed fresh tissue rapidly. OBJECTIVE: Evaluation of the process to
      generate and analyse CLSM images and assessment of the accuracy to detect basal
      cell carcinoma (BCC) tissue. METHODS: Digital microscopic images were generated
      by the Histolog Scanner v1 from 544 fresh specimens of 148 BCCs that had been
      stained with a 0.01% proflavine solution. CLSM images were compared to the
      histological diagnoses of the corresponding H&E-stained slides. RESULTS: A total
      of 525 images could be analysed. The sensitivity was 73% (95% CI = [65.27%;
      80.47%]), and the specificity was 96% (95% CI = [93.40%; 97.60%]). Detection of
      BCCs in punch biopsies was certainly detected (sensitivity of 100%). The median
      total time to generate and evaluate a CLSM image was 5.17 min (maximum 20.17 min
      and minimum 2.05 min). The greatest challenge was flattening the specimen to
      assure complete representation of the surgical margins. CONCLUSION: Confocal
      laser scanning microscopy is a time-saving and very effective alternative to
      classical paraffin-embedded or frozen sections. Patient treatment could be
      improved due to shorter hospital stays or faster outpatient therapy due to
      reduced intervals between surgical stages. Diagnostic accuracy of the microscope
      used still must be improved.

PMID- 30198591
TI  - Local enactments of national health promotion policies: A Danish case.
AB  - Governments of welfare states are firmly committed to public health, resulting in
      a substantial number of public health policies. Given the multilevel structure of
      most welfare systems, the influence of a public health policy is related to its
      ability to spread geographically and move across organisational levels. Visiting,
      observing, and interviewing 15 policy workers from 10 municipalities during a 2
      year period, this study investigated what happened to a Danish national health
      promotion policy as it was put into practice and managed in the Danish
      municipalities. The analysis reveals that the policy was practiced in at least 5
      different ways: as an ideal, a cookbook, a tangible artefact, a creative
      deconstruction, and a mapping. The various practices each enacted a different
      version of this policy, and some of these enactments brought unintended but
      valuable effects. Without recognising the concrete enactments and their locally
      experienced effects, our understanding of national public health policies risks
      becoming detached from praxis and unproductive. Public health policy makers must
      pay methodological and analytical attention to the policies' multimodality and
      their concrete locally experienced effects.

PMID- 30198590
TI  - A Comparison of the chemical sensitivities between in vitro and in vivo
      propagated juvenile freshwater mussels: Implications for standard toxicity
      testing.
AB  - Unionid mussels are ecologically important and are globally imperiled. Toxicants
      contribute to mussel declines, and toxicity tests using juvenile mussels-a
      sensitive life stage-are valuable in determining thresholds used to set water
      quality criteria. In vitro culture methods provide an efficient way to propagate
      juveniles for toxicity testing, but their relative chemical sensitivity compared
      with in vivo propagated juveniles is unknown. Current testing guidelines caution
      against using in vitro cultured juveniles until this sensitivity is described.
      Our objective was to evaluate the relative sensitivity of juvenile mussels
      produced from both in vitro and in vivo propagation methods to selected
      chemicals. We conducted 96-h acute toxicity tests according to ASTM International
      guidelines with 3 mussel species and 6 toxicants: chloride, nickel, ammonia, and
      3 copper-based compounds. Statistically significant differences between in vitro
      and in vivo juvenile 96-h median effect concentrations were observed in 8 of 17
      tests, and in vitro juveniles were more sensitive in 6 of the 8 significant
      differences. At 96 h, 4 of the 8 statistically different tests for a given
      chemical were within a factor of 2, which is the intralaboratory variation
      demonstrated in a recent evaluation of mussel toxicity tests. We found that
      although differences in chemical sensitivity exist between in vitro and in vivo
      propagated juvenile mussels, they are within normal toxicity test variation.
      Therefore, in vitro propagated juvenile mussels may be appropriate for use in
      ASTM International-based toxicity testing. Environ Toxicol Chem 2018;37:3077
      3085. (c) 2018 SETAC.

PMID- 30198592
TI  - Modelling the executive components involved in processing false belief and
      mechanical/intentional sequences.
AB  - To understand the executive demands of the false-belief (FB) task relative to an
      alternative theory-of-mind (or mechanical causality) task, picture sequencing,
      the present study used path analyses. One hundred and sixty-six children between
      3 and 6 years old completed the FB and picture-sequencing tasks, three executive
      function tasks (updating, inhibition, and shifting), and the receptive language
      test. The model with the best fit indicated that FB performance had a direct
      contribution from shifting of attention and inhibitory control, which was
      independent of the significant contribution made by picture sequencing. This
      model indicates that FB inference requires more executive processing than picture
      sequencing, which is used as an alternative task to measure theory of mind.
      Statement of contribution What is already known on this subject? The majority of
      researchers use the false-belief task to assess mentalizing ability in young
      children. Sources of information used in various different mentalizing tasks
      require different levels of cognitive demand. Many executive functions (EFs) are
      involved in children's judgements of false belief. What does this study add? A
      statistical model was created to compare processing requirements of false-belief
      and picture-sequencing tasks. The model supported the claim that the false-belief
      task involves considerably more than just mentalizing. Shifting the focus of
      attention was an EF that was found to be a key component of performance in the
      false-belief task.

PMID- 30198593
TI  - Responding to a national policy need: development of a stigma indicator for
      bloodborne viruses and sexually transmissible infections.

PMID- 30198594
TI  - Ethics and HIV prevention research: An analysis of the early tenofovir PrEP trial
      in Nigeria.
AB  - In 2004, the first ever multi-sited clinical trials studied the prospect of HIV
      biomedical prevention (referred to as pre-exposure prophylaxis-'PrEP'). The
      trials were implemented at several international sites, but many officially
      closed down before they completed. At most sites, both scientists and community
      AIDS advocates raised concerns over the ethics and scientific rationales of the
      trial. Focusing on the Nigerian trial site, we detail the controversy that
      emerged among mostly Nigerian research scientists who scrutinized the research
      design and protocol. While some of the disputes, especially those pertaining to
      community engagement mechanisms, were ultimately resolved in international fora
      and implemented in later PrEP trials, concerns over science rationales and
      assumptions were never addressed. We argue that scientific rationales should be
      treated as ethical concerns and suggest that such concerns should be deliberated
      at host sites before the trial protocol is finalized.

PMID- 30198595
TI  - Development of a physiologically based pharmacokinetic model for mefloquine and
      its application alongside a clinical effectiveness model to select an optimal
      dose for prevention of malaria in young Caucasian children.
AB  - AIMS: To predict the optimal chemoprophylactic dose of mefloquine in infants of 5
      10 kg using physiologically based pharmacokinetic (PBPK) and clinical
      effectiveness models. METHODS: The PBPK model was developed in Simcyp version
      14.1 and verified against clinical pharmacokinetic data in adults; the final
      model, accounting for developmental physiology and enzyme ontogeny was then
      applied in the paediatric population. The clinical effectiveness model utilized
      real-world chemoprophylaxis data with stratification of output by age and
      including infant data from the UK population. RESULTS: PBPK simulations in infant
      populations depend on the assumed fraction of mefloquine metabolized by CYP3A4
      (0.47, 0.95) and on the associated CYP3A4 ontogeny (Salem, Upreti). However, all
      scenarios suggest that a dose of 62.5 mg weekly achieves or exceeds the exposure
      in adults following a 250 mg weekly dose and results in a minimum plasma
      concentration of 620 ng ml-1 , which is considered necessary to achieve 95%
      prophylactic efficacy. The clinical effectiveness model predicts a 96% protective
      efficacy from mefloquine chemoprophylaxis at 62.5 mg weekly. CONCLUSIONS: The
      PBPK and clinical effectiveness models are mutually supportive and suggest a
      prophylactic dose of 62.5 mg weekly in the Caucasian 5-10 kg infant population
      travelling to endemic countries. This dual approach offers a novel route to dose
      selection in a vulnerable population, where clinical trials would be difficult to
      conduct.

PMID- 30198596
TI  - Successful treatment of resistant condylomas with nitrizinc complex solution: a
      retrospective study in 11 patients.

PMID- 30198597
TI  - Bidirectional relationship between caregiver burden and neuropsychiatric symptoms
      in patients with Alzheimer's disease: A narrative review.
AB  - OBJECTIVE: The aim of this review is to make a state of the art of the potential
      influence of neuropsychiatric symptoms (NPs) on caregiver stress and vice versa.
      METHODS: We searched PubMed and Google Scholar for potential eligible articles.
      RESULTS: Patients with Alzheimer's disease (AD) usually need high levels of care
      in all activities of daily living, most of them provided by family members,
      friends, or informal caregivers. Caregivers have to cope with both age-related
      conditions and dementia-related factors. Therefore, caregiving in dementia is
      more difficult and stressful than caregiving for older adults, affected by other
      conditions. Neuropsychiatric symptoms, such as anxiety, agitation, disinhibition,
      aggressive behavior, and sleep disturbances are more closely related to caregiver
      burden, and associated with more negative outcomes such as decline in their
      general health, quality of life, and social isolation. Caregiver burden worsens
      relationship between caregiver and patients with AD. Thus, this relationship may
      increase the frequency and severity of NPs. Predictors of burden were being a
      woman, a spouse, and old person with immature coping mechanisms, social
      isolation, with insufficient knowledge about dementia, poor premorbid
      relationship with patient, and high levels of negative expressed emotions.
      CONCLUSION: Because of the bidirectional relationship between caregiver burden
      and NPs, the active management strategies of dementia care should include early
      identification and treatment risk factors for both caregiver stress and NPs in
      patients with AD. Therefore, to improve one of them can be exert beneficial for
      the other.

PMID- 30198598
TI  - Clinical outcomes in patients on secukinumab (Cosentyx(r) ) within a specialist
      psoriasis clinic: a single centre, retrospective cohort study.

PMID- 30198599
TI  - Organisational cultural competence needed to care for foreign patients: A focus
      on nursing management.
AB  - AIM: This study aimed to explore the organisational level of the cultural
      competence needed to care for foreign patients from the Korean clinical
      registered nurses' perspective. BACKGROUND: Owing to the increasing foreign
      resident population in Korea, health care organisations face challenges arising
      from cultural differences. However, there is a lack of research on the impact of
      these changes on nursing care and management. METHOD: Participants were 16
      clinical registered nurses from six general hospitals. Data were collected
      through individual in-depth and focus group interviews. Transcribed data were
      analysed by deductive content analysis. RESULTS: Data were classified into three
      categories: information, resources and incentives. Information included a
      systematic staff training programme and clear practice guidelines. Resources
      included convenient and credible interpretation services and adequate tools and
      materials, and incentives were referred to managerial support. CONCLUSION: Korean
      registered nurses perceived a lack of organisational support for caring for
      foreign patients. System-wide support and active unit-level intervention of
      nursing managers are essential for successful transformation towards a culturally
      competent organisation. IMPLICATION FOR NURSING MANAGEMENT: Registered nurses
      should play leadership roles to establish a dedicated nursing team or committee
      to create a supportive working environment and implement a monitoring system so
      that their organisations move towards greater cultural competence.

PMID- 30198600
TI  - Endochondral ossification in hindlimbs during bufo gargarizans metamorphosis: A
      model of studying skeletal development in vertebrates.
AB  - Background Endochondral ossification, the process by which most of the skeleton
      is formed, is accurately regulated by many specific groups of molecules and
      extracellular matrix components. The molecular mechanisms of endochondral
      ossification have been extensively investigated in mammals. However, there are
      few studies about it in amphibians. Results Ossification of femur and tibiofibula
      was observed at Gs 40, and tarsals and metatarsals were ossified at Gs 42. Most
      of the skeletons in hindlimbs were completely ossified except for articular
      cartilages at Gs 46. Thirty-two genes related to endochondral ossification were
      found in the differentially expressed genes (DEGs) library of hindlimbs, and nine
      of these genes were validated by qRT-PCR during metamorphosis. Sox9 was expressed
      in the columnar, prehypertrophic, and upper hypertrophic zones, and the
      expression of Ihh was observed in prehypertrophic chondrocyte zone in hindlimbs
      of B. gargarizans. Conclusions The ossification of hindlimbs increased gradually,
      and the ossification sequence was from proximal to distal in B. gargarizans
      during metamorphosis. Thirty-two genes found in the DEGs library were related to
      the regulation of endochondral ossification of hindlimbs in amphibians. The
      present study will provide a valuable genomic resource for the future study of
      endochondral ossification in amphibian. Developmental Dynamics 247:1121-1134,
      2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 30198601
TI  - Prospective Study of the Clinical, Electrophysiologic, and Sonographic
      Characteristics of Oxaliplatin-Induced Neuropathy.
AB  - BACKGROUND AND PURPOSE: Oxaliplatin-induced neuropathy is a major dose limiting
      side effect of the highly effective combination chemotherapy with oxaliplatin,
      irinotecan, and 5-fluorouracil (FOLFIRINOX) in patients with metastastic
      pancreatic cancer. We present the first longitudinal sonographical
      electrophysiological study on oxaliplatin-induced neuropathy. METHODS: Thirteen
      patients with metastatic pancreatic cancer underwent clinical, sonographic, and
      electrophysiological evaluation before, 3 and 7 months after treatment with 12
      two-week cycles of FOLFIRINOX. RESULTS: The majority of patients (61%) developed
      symptoms and electrophysiological signs of a length-dependent sensorimotor axonal
      neuropathy 7 months after treatment initiation. Oxaliplatin-induced neuropathy
      presented with a cross-sectional area (CSA) increase of mostly the tibial and
      fibular nerve, which developed parallel or prior to clinical signs and
      electrophysiological changes. Furthermore, isolated CSA at entrapment sites of
      the upper and lower extremities was measured without relevant symptoms. No
      correlation between sonographic and electrophysiological findings or clinical
      severity was detected. CONCLUSIONS: Oxaliplatin-induced neuropathy is
      characterized by an axonal length-dependent nerve affection presenting with a
      combination of sonographical and electrophysiological alterations.

PMID- 30198602
TI  - Cultural and linguistic diversity of people living with chronic hepatitis B in
      2011-2016: changing migration, shifting epidemiology.
AB  - OBJECTIVE: To estimate the cultural and linguistic diversity in Australians
      currently living with chronic hepatitis B (CHB), the majority of whom were born
      overseas, and to identify trends in this diversity over time. METHODS: Estimates
      were generated by combining Australian census country of birth information with
      seroprevalence data generated from antenatal serology linked with surveillance
      notifications. The number of people living with CHB was assessed according to
      country of birth using the 2011 and 2016 censuses. RESULTS: The total number of
      Australian residents living with CHB increased by 20% between 2011 and 2016,
      substantially outpacing population growth. The most common country of birth
      continued to be China, with the number of Chinese-born Australians living with
      CHB increasing by 60% in the 5-year period. Decreased numbers were observed for
      people born in European countries. CONCLUSIONS: The epidemiology of chronic
      hepatitis B in Australia has shifted over time due to changing migration
      patterns, with increases in many countries in the Asia-Pacific, African and
      Middle Eastern regions. Implications for public health: Interventions to improve
      the health of people living with CHB are imperative, and these up-to-date
      estimates identify priority groups and communities, which are constantly
      changing.

PMID- 30198603
TI  - Associations between gait speed and well-known fall risk factors among community
      dwelling older adults.
AB  - BACKGROUND AND PURPOSE: Exercise interventions are effective at preventing falls
      in community-dwelling older adults, especially before disability is present. Gait
      speed below 1.0 m/s is a strong predictor for falls in the elderly. However,
      evidence is sparse for gait speed alone being sufficient to identify individuals
      at a high risk of falling. This study aimed to describe the prevalence of fall
      risk factors among community-dwelling older adults in their late 70s and to
      investigate the associations between these risk factors and low gait speed in
      this population. METHODS: This cross-sectional cohort study comprised 108 elderly
      living in a small Norwegian municipality, born between 1936 and 1938. Exclusion
      criteria were living in residential care, inability to walk 4 m, and severe
      cognitive impairment. Measurements included gait speed, depressive symptoms,
      executive functions, fear of falling, vision function, fall history, body mass
      index, medications, and comorbidity. Gait speed was dichotomized using a cut-off
      of 1 m/s, and associations between different risk factors and low gait speed was
      explored using logistic regression analysis. RESULTS: Mean gait speed was 1.0 +/-
      0.3 m/s. In 44.4% of the participants, gait speed was below 1.0 m/s, indicating
      increased fall risk. Low gait speed was significantly associated with a history
      of multiple falls (odds ratio [OR] = 3.70, 95% CI [1.18, 11.65]), low educational
      level (OR = 3.58, 95% CI [1.10, 11.66]), higher number of medications (OR = 4.28,
      95% CI [1.63, 11.2]), and higher number of depressive symptoms (OR = 1.31, 95% CI
      [1.09, 1.58]). We found no significant associations between gait speed and
      comorbidity, sex, vision, executive functions, or fear of falling. CONCLUSION:
      Our results indicate that gait speed with cut-off 1.0 m/s could represent a
      useful tool for identifying individuals who are vulnerable but not yet disabled
      and could benefit from fall-preventive exercise. However, extended assessment is
      probably needed to personalize interventions.

PMID- 30198604
TI  - Preventing disaster in the Pacific Islands: the battle against climate
      disruption.

PMID- 30198605
TI  - Knowledge of current abortion law and views on abortion law reform: a community
      survey of NSW residents.
AB  - OBJECTIVE: To report results of a community survey of NSW residents' knowledge of
      current abortion law and views on abortion law reform. METHODS: A total of 1,015
      men and women participated. Recruitment and questionnaires were completed
      anonymously online using survey panel sampling. RESULTS: Seventy-six per cent of
      respondents were unaware that abortion remains a criminal offence in the Crimes
      Act 1900 (NSW) and 73% thought it should be decriminalised and regulated as a
      healthcare service. Support for decriminalisation was consistent across genders,
      age groups, residents of metropolitan/regional and rural areas and levels of
      education. Support was strong for women seeking abortion to be protected from
      harassment (89%) and for protester exclusion zones around clinics (81%), with
      support for these measures significantly stronger among regional/rural residents
      than Sydney-based respondents. CONCLUSIONS: Abortion law in NSW is out of step
      with contemporary community views. Residents are largely unaware that it remains
      a criminal offence and, when informed, support decriminalisation. There is strong
      support for legal changes to protect women from harassment and to provide
      protester exclusion zones around abortion clinics. Implications for public
      health: Abortion law reform would reduce current inequities of access, be
      democratic and support women's autonomy and reproductive rights.

PMID- 30198606
TI  - A case series to investigate food-related fear learning and extinction using in
      vivo food exposure in anorexia nervosa: A clinical application of the inhibitory
      learning framework.
AB  - OBJECTIVE: Anorexia nervosa is characterized by severe malnutrition. This study
      tested the hypothesis that fear of food is a learned behaviour and evaluated the
      feasibility and effectiveness of gradual exposure to food to improve eating
      behaviour in people with anorexia nervosa. METHODS: Eighteen women were recruited
      and completed baseline self-reports. They were interviewed regarding early
      experiences of eating and the development of food-related anxiety. Participants
      received eight sessions of in vivo food exposure. RESULTS: Findings indicated
      that fear of food is a learned behaviour, associated with catastrophic thoughts
      around the consequences of eating and safety behaviours. Patients consumed at
      least half of the food item selected in all but one session. Body mass index
      increased, and food restriction, eating concern, eating disorder-related
      preoccupations, and overall anxiety reduced (medium/large ES). CONCLUSION:
      Findings corroborate an anxiety-based model of anorexia nervosa and support the
      relevance of targeting food-related fears using exposure-based protocols.

PMID- 30198607
TI  - Red blood cell exchange in patients with sickle cell disease-indications and
      management: a review and consensus report by the therapeutic apheresis subsection
      of the AABB.
AB  - BACKGROUND: A prior practice survey revealed variations in the management of
      patients with sickle cell disease (SCD) and stressed the need for comprehensive
      guidelines. Here we discuss: 1) common indications for red blood cell exchange
      (RCE), 2) options for access, 3) how to prepare the red blood cells (RBCs) to be
      used for RCE, 4) target hemoglobin (Hb) and/or hematocrit (Hct) and HbS level, 5)
      RBC depletion/RCE, and 6) some complications that may ensue. STUDY DESIGN AND
      METHODS: Fifteen physicians actively practicing apheresis from 14 institutions
      representing different areas within the United States discussed how they manage
      RCE for patients with SCD. RESULTS: Simple transfusion is recommended to treat
      symptomatic anemia with Hb level of less than 9 g/dL. RCE is indicated to prevent
      or treat complications arising from the presence of HbS. The most important goals
      are reduction of HbS while also preventing hyperviscosity. The usual goals are a
      target HbS level of not more than 30% and Hct level of less than 30%. CONCLUSION:
      Although a consensus as to protocol details may not be possible, there are areas
      of agreement in the management of these patients, for example, that it is optimal
      to avoid hyperviscosity and iron overload, that a target Hb S level in the range
      of 30% is generally desirable, and that RCE as an acute treatment for pain crisis
      in the absence of other acute or chronic conditions is ordinarily discouraged.

PMID- 30198608
TI  - Acute hyperleukocytic leukemia with numerous blast fragments can mask
      thrombocytopenia.

PMID- 30198609
TI  - Genotypic and phenotypic characteristics of Escherichia coli involved in
      transfusion-transmitted bacterial infections: implications for preventive
      strategies.
AB  - BACKGROUND: Transfusion-transmitted bacterial infections (TTBIs) are the main
      residual infectious complications of transfusions. Escherichia coli and platelet
      (PLT) concentrates may be epidemiologically associated, leading to severe, if not
      lethal, TTBIs. We investigated the genotypic and phenotypic reasons for this
      clinically deleterious combination. STUDY DESIGN AND METHODS: We investigated a
      French national E. coli strain collection related to six independent episodes of
      TTBIs. Their phenotypic characterizations included antibiotic susceptibility
      testing, growth testing under different culture conditions, serum survival
      assays, and virulence in a sepsis mouse model. Their genotypic characterizations
      included polymerase chain reaction phylotyping, whole genome sequencing, and a
      subsequent in silico analysis. RESULTS: We highlighted a selection process of
      highly extraintestinal virulent strains, mainly belonging to the B2 phylogroup,
      adapted to the hostile environment (high citrate concentration and a bactericidal
      serum effect) of apheresis-collected platelet concentrates (PCs). Compared to
      controls, the E. coli TTBI strains grew faster in the PCs due to a superior
      ability to capture iron. The in vitro growth performances were highly compatible
      with blood-derived product real-life conditions, including storage conditions and
      delays. The consistent serum resistance of TTBI strains promotes their survival
      in both the donor's and the receiver's blood and in the PCs. CONCLUSION: This
      study pointed out that E. coli strains responsible for TTBI exhibit very specific
      traits. They belong to the extraintestinal pathogenic phylogroups and have a high
      intrinsic virulence. They can be resistant to complement, capture iron, and grow
      in the apheresis-collected PCs. These findings therefore support the
      reinforcement of the postdonation information.

PMID- 30198610
TI  - Severe iron deficiency anemia: red blood cell transfusion or intravenous iron?

PMID- 30198611
TI  - Targeted prospective hepatitis C virus "lookback" program: is it an efficient and
      effective use of resources?

PMID- 30198613
TI  - Fibrin in blood samples interferes with blood grouping by automation.

PMID- 30198615
TI  - False-positive negative control in a direct antiglobulin test.

PMID- 30198616
TI  - PHAA's Health Equity Policy.

PMID- 30198618
TI  - Effect of a punctal plug on ocular surface disease in patients using topical
      prostaglandin analogues: A randomized controlled trial -Response.

PMID- 30198617
TI  - Group mentorship programme for graduating nursing students to facilitate their
      transition: A pilot study.
AB  - AIM: The present study aims to describe and evaluate a group mentorship programme
      for graduating nursing students following the first pilot testing. BACKGROUND: A
      mentoring relationship has been found to be beneficial in easing the challenging
      transition from nursing student to nurse. However, very few mentoring programmes
      have been formally developed to pair students with clinical nurses before
      graduation. METHODS: A group mentoring programme for graduating nursing students
      was developed where clinical nurse mentors met with student mentees twice before
      graduation and once shortly after graduation to address relevant challenges.
      Mentees and mentors completed a survey after the last session. RESULTS: Eighteen
      mentees and 12 mentors completed the survey. Results suggest a high level of
      satisfaction with the programme from both mentees and mentors, as well as a
      positive impact on mentees' transition into the workplace and levels of stress
      and self-confidence. CONCLUSIONS: The pilot testing of the group mentorship
      programme is believed to have been successful. IMPLICATIONS FOR NURSING
      MANAGEMENT: This pilot project highlights the value to nursing leadership of
      group mentoring partnerships between academic and clinical settings, which can
      improve the integration of new nurses in the workplace and increase mentors'
      awareness of the needs of these nurses.

PMID- 30198619
TI  - Nurses' perceptions of mandatory bedside clinical handovers: An Australian
      hospital study.
AB  - AIMS: The research explores (a) nurses' views of the change to mandatory bedside
      handovers, and (b) these nurses' perceptions of their skills in managing this new
      practice in an Australian hospital. BACKGROUND: In Australia, nursing bedside
      handovers are now considered essential in many hospitals, although most nurses
      received minimal training at the time this policy was instituted. This research
      establishes a unique quantitative tool to investigate nurses' views of, and self
      reported actions related to, bedside handovers. METHOD: Prior to the
      implementation of mandatory bedside handovers in a hospital in Canberra,
      Australia, nurses in two wards (n = 66) were recruited to complete the new
      Bedside Handover Attitudes and Behaviours (BHAB) questionnaire. RESULTS: Most
      nurses strongly value bedside handovers and have confidence in their ability to
      lead this clinical practice. CONCLUSIONS: Researchers identified a high level of
      alignment between the nurses' acceptance of bedside handovers and nurses' self
      reported actions in conducting this communication process. IMPLICATIONS FOR
      NURSING MANAGEMENT: Future research should explore the links between nurses'
      views of, and skills in, the management of bedside handovers, as well as the
      effects of professional training for this practice. Furthermore, the BHAB
      questionnaire may be employed in different nursing contexts in future research.

PMID- 30198620
TI  - Removal of sugary drinks from vending machines: an Australian university case
      study.

PMID- 30198621
TI  - Carbohydrates and Charges on Oligo(phenylenethynylenes): Towards the Design of
      Cancer Bullets.
AB  - Two new tetralkylammonium-OPEs, bearing one or two positively charged groups
      directly linked to the aromatic residues and two beta-d-glucopyranose
      terminations, were synthesized. Their peculiar structural features, joining the
      biologically relevant sugar moieties, flat aromatic cores and positive charges,
      make these luminescent dyes soluble in aqueous media and able to strongly
      interact with DNA. As a result of UV/Vis spectral variations, DNA melting
      temperature measures, viscometric titrations and induced CD, we propose a partial
      insertion of the OPEs aromatic core into the helix, stabilized by glucose H
      bonding with the groups accessible from the grooves. This interaction leads to
      the quenching of the OPE luminescence due to guanine reduction. The
      biocompatibility of the monocationic OPE with healthy and cancer cells, and the
      reduction of proliferation in HEp-2 cancer cells induced by the dicationic one,
      make this class of compounds promising for future biological applications.

PMID- 30198622
TI  - A threonine zipper that mediates protein-protein interactions: Structure and
      prediction.
AB  - We present the structure of an engineered protein-protein interface between two
      beta barrel proteins, which is mediated by interactions between threonine (Thr)
      residues. This Thr zipper structure suggests that the protein interface is
      stabilized by close-packing of the Thr residues, with only one intermonomer
      hydrogen bond (H-bond) between two of the Thr residues. This Thr-rich interface
      provides a unique opportunity to study the behavior of Thr in the context of many
      other Thr residues. In previous work, we have shown that the side chain (chi1 )
      dihedral angles of interface and core Thr residues can be predicted with high
      accuracy using a hard sphere plus stereochemical constraint (HS) model. Here, we
      demonstrate that in the Thr-rich local environment of the Thr zipper structure,
      we are able to predict the chi1 dihedral angles of most of the Thr residues.
      Some, however, are not well predicted by the HS model. We therefore employed
      explicitly solvated molecular dynamics (MD) simulations to further investigate
      the side chain conformations of these residues. The MD simulations illustrate the
      role that transient H-bonding to water, in combination with steric constraints,
      plays in determining the behavior of these Thr side chains. Broader Audience
      Statement: Protein-protein interactions are critical to life and the search for
      ways to disrupt adverse protein-protein interactions involved in disease is an
      ongoing area of drug discovery. We must better understand protein-protein
      interfaces, both to be able to disrupt existing ones and to engineer new ones for
      a variety of biotechnological applications. We have discovered and characterized
      an artificial Thr-rich protein-protein interface. This novel interface
      demonstrates a heretofore unknown property of Thr-rich surfaces: mediating
      protein-protein interactions.

PMID- 30198623
TI  - Characterization, distribution, antimicrobial resistance and resistance risk
      factors in staphylococci isolated from cats from 2001 to 2014.
AB  - Relatively few studies have been published describing the patterns of
      staphylococcal isolation and antimicrobial resistance over time in cats. The
      objective of this retrospective study was to determine the frequency, location,
      characteristics and antimicrobial resistance profiles of staphylococci isolated
      by the Louisiana Animal Disease Diagnostic Laboratory between the years 2001 and
      2014. All feline staphylococcal isolates were classified phenotypically. Isolates
      corresponding to known or possibly pathogenic species (Staphylococcus intermedius
      group (SIG) and Staphylococcus aureus (SA)) as well as Staphylococcus epidermidis
      (SE) and non-speciated coagulase-negative staphylococci (CNS) were further
      evaluated to determine antimicrobial resistance patterns. A total of 519
      staphylococci were isolated. The largest percentage of isolates was CNS,
      representing 39.3% of the total, while SIG, SE, SA and non-speciated coagulase
      positive staphylococci (CPS) represented 18.1%, 10.2%, 8.3% and 7.3%,
      respectively. Methicillin resistance (MR) was identified in 57.1% of SA and 20.5%
      of SIG. Resistance to 3 or more antimicrobial classes (multidrug resistance; MDR)
      was demonstrated in 54.5% of SA and 23.9% of SIG. The prevalence of MDR increased
      over time in both SIG and SA, while the prevalence of MR increased over time in
      SIG. An increase in mean antimicrobial resistance score over time was seen in
      SIG. This study demonstrates a high and increasing prevalence of MDR in SIG and
      SA, as well as increasing prevalence of MR in SIG isolated from cats.

PMID- 30198624
TI  - Critical thinking: A comparative analysis between nurse managers and registered
      nurses.
AB  - AIM: To analyse the levels of critical thinking among nurse managers and
      registered nurses and to explore the association between these levels and socio
      demographic and occupational factors. BACKGROUND: Critical thinking is an
      essential skill in advanced clinical nursing. However, few studies to date have
      explored critical thinking levels in nurse managers or compared them with those
      recorded in registered nurses. METHODS: A randomized sample of 44 nurse managers
      and 295 registered nurses from a tertiary hospital in Barcelona participated in
      this study. The Nursing Critical Thinking in Clinical Practice Questionnaire was
      used to measure the level of critical thinking. The data were analysed using
      multivariate analysis by logistic regression. RESULTS: Levels of critical
      thinking were higher in nurse managers than in registered nurses. Age, work shift
      schedule and educational level were associated with a higher level of critical
      thinking in nurse managers and were predictor factors. CONCLUSIONS: This study
      identified age, work shift schedule and educational level as factors that impact
      on the acquisition of critical thinking skills among nurse managers. IMPLICATIONS
      FOR NURSING MANAGEMENT: This study provides substantive evidence of the levels of
      critical thinking among nurse managers. When introducing strategies to enhance
      these skills, the associated occupational factors should be taken into account.

PMID- 30198625
TI  - Nurses' characteristics and practice environments: Comparison between clusters
      with different attitude and utilisation profiles regarding nursing diagnosis.
AB  - AIM: To identify clusters of nurses in relation to the utilisation and attitude
      towards nursing diagnosis and to compare their profiles considering demographics,
      professional characteristics and nursing practice environments. BACKGROUND:
      Nursing diagnosis has benefits for both patients and nurses, and the attitude of
      nurses towards nursing diagnosis has been proposed as a determinant of its use.
      Therefore, an adequate understanding of nurses' attitude and utilisation profiles
      regarding nursing diagnosis is essential for the nursing managers who want to
      adopt nursing diagnosis as a practice framework. METHODS: A cross-sectional
      survey design was used. A sample of 239 nurses working in the Catalan primary
      health care system were categorised into clusters with similar attitude and
      utilisation profiles, which were compared with each other a posteriori. RESULTS:
      Nursing managers were grouped into more positive attitude clusters than clinical
      nurses. Nurses working in supportive nursing practice environments were
      classified into more positive attitude and higher utilisation clusters.
      CONCLUSION: The field of work and nursing practice environments were found as
      differential factors in profiles of nurses with different attitudes towards
      and/or utilisation of nursing diagnosis. IMPLICATIONS FOR NURSING MANAGEMENT: The
      promotion of supportive nursing practice environments could enhance the
      implementation and maintenance of nursing diagnosis as a practice framework in
      primary health care.

PMID- 30198626
TI  - Reversible Photocontrol of DNA Melting by Visible-Light-Responsive F4-Coordinated
      Azobenzene Compounds.
AB  - Spatiotemporal control over the regulation of intra- and intermolecular motions
      in naturally occurring systems is systematically studied to expand the toolbox of
      mechanical operations in multicomponent nanoarchitectures. DNA is ideally suited
      for programming light-powered processes that are based on a minimalist molecular
      design. Here, the noncovalent incorporation of bistable photoswitches into B-like
      DNA moieties is shown to trigger the thermal transition midpoint of the duplexes
      by converting visible light into directed mechanical work by orchestrating the
      collective actions of the photoresponsive chromophores and the host DNA
      nanostructures. Besides its practical applications, the resulting hybrid
      nanosystem bears unique features of modulability, biocompatibility,
      reversibility, and addressability, which are key components for developing
      molecular photon-controlled programmed materials.

PMID- 30198627
TI  - Weight loss, behavioral change, and structural neuroplasticity in children with
      obesity through a multidisciplinary treatment program.
AB  - This study evaluated the effect of a multidisciplinary treatment program for
      children with obesity (OB) on motor competence, executive functioning (EF), and
      brain structure. Nineteen children with OB (7-11 years), who attended a
      multidisciplinary treatment program consisting of diet restriction, cognitive
      behavioral therapy, and physical activity, were compared with an age-matched
      control group of 24 children with a healthy weight (HW), who did not follow any
      treatment. For both groups, anthropometric measurements and tests of motor
      competence and EF were administered twice, with 5 months between pretest and
      posttest. Additionally, children's brain structure was assessed by performing a
      magnetic resonance imaging (MRI) scan at the pretest and posttest, which included
      a T1 anatomical scan, diffusion MRI scan, and magnetization transfer imaging
      scan. Compared to HW controls, children with OB lost a considerable amount of
      their body mass (p <= .001) and significantly improved their balance skills (p <=
      .001), while no transfer effects of the program were observed for EF.
      Furthermore, the program resulted in a significant increase in total (p <= .001)
      and cerebellar (p <= .001) gray matter volume in children with OB, while no
      change was observed in the HW controls. Finally, only weak to moderate
      (nonsignificant) correlations could be observed between structural brain
      alterations, weight-related changes, and behavioral improvements. Altogether,
      this is the first longitudinal study showing behavioral and structural brain
      alterations in response to a multidisciplinary weight loss program for children
      with OB. Our findings support the need for multidimensional intervention (and
      prevention) measures for children with OB to deal with this multifactorial health
      problem.

PMID- 30198628
TI  - A review of factors influencing radiologists' visual search behaviour.
AB  - This narrative literature review aims to identify the various factors that have
      significant impact on radiologists' visual search patterns. Identifying the
      factors that influences readers' visual search behaviour helps to understand
      their perception and interpretation of medical images, which in turn could lead
      to the development and implementation of effective strategies that could aid in
      improving the ability to detect abnormalities. Databases including PubMed,
      MedLine, Web of Science and ScienceDirect were searched using terms 'visual
      search', 'eye-tracking', 'radiology OR radiography', 'mammogram OR mammography'
      published since the early 1960s until June 30, 2016. Some of the factors that
      have been identified to significantly influence radiologists' visual search
      patterns were (i) readers' expertise, (ii) Satisfaction of Search, (iii) readers'
      visual fatigue, (iv) readers' confidence in reporting abnormalities, (v) training
      received and (vi) readers' prior knowledge. Readers' level of expertise was the
      factor that has been identified to have the most significant impact on their
      visual search pattern. Eye-tracking studies have shown the differences in visual
      search patterns of readers with different levels of experience and not so
      surprisingly, more experienced readers have shown effective visual search
      strategies. Readers' expertise has also been found to have significant impact in
      their confidence in reporting abnormalities and their ability to discriminate
      lesions from background structures in medical images.

PMID- 30198629
TI  - Development of Capacitance Tools: At-Line Method for Assessing Biomass of
      Mammalian Cell Culture and Fixed Cell Calibration Standard.
AB  - Capacitance is used to monitor "biomass" in cell culture and fermentation
      processes. The present work explores various ways to support good manufacturing
      practices (GMP) use and create robust methods that can assure proper performance
      of capacitance equipment. An at-line capacitance measurement method is
      particularly valuable as it can be used to correct or confirm online measurements
      from bioreactors. To obtain consistent predictions of online capacitance, the at
      line method requires appropriate control of culture temperature, vessel geometry,
      mixing, and timing. The at-line method yields values that differ systematically
      from online values, but the variation is <=11% for two cell lines tested. A cell
      line-specific conversion factor addresses the difference and enables accurate
      predictions of online capacitance values. In addition to the at-line method,
      verification of equipment performance is further enabled by using formaldehyde
      treated cell standards. The cell-derived standards create a stabilized system for
      studying capacitance and recapitulate the performance of metabolically active
      cell culture. The formaldehyde-treated cells, however, require a much greater
      conversion factor to predict online outputs. The stabilized system proves useful
      for evaluation and calibration of capacitance measuring systems. The at-line
      method and stabilized cell-derived suspensions support use of capacitance for
      process control in large scale mammalian cell culture.

PMID- 30198630
TI  - Understanding how the concentration of neighborhood advantage and disadvantage
      affects spina bifida risk among births to non-Hispanic white and Hispanic women,
      Texas, 1999-2014.
AB  - BACKGROUND: This is the first study to utilize the index of concentration at the
      extremes (ICE) to examine risk factors for spina bifida in Texas. The ICE is a
      useful measure for providing the degree to which residents in a certain area are
      concentrated into groups at the extremes of disadvantage and privilege. We
      introduce two novel ICE measures (language and nativity), and three existing ICE
      measures (race/ethnicity, income, and education), which we applied specifically
      to Texas residents. METHODS: We used multivariable mixed-model Poisson regression
      analyses to estimate spina bifida birth prevalence and prevalence ratios among
      singleton live births in Texas, 1999-2014, for each of our ICE measures. Maternal
      census tract at delivery was included in the models as a random effect. Analyses
      were stratified by maternal race/ethnicity (Hispanics and non-Hispanic whites).
      Live births served as denominators for each category. RESULTS: Among non-Hispanic
      white women, those in the most disadvantaged versus the advantaged census tract
      quintile had adjusted relative risk between 1.6 and 8.5 for having a baby
      affected by spina bifida. However, Hispanic women in the most disadvantaged
      versus advantaged census tract quintile for four ICE measures had a 33% to 87%
      lower risk of having an affected pregnancy. CONCLUSIONS: Findings suggest spina
      bifida risk is associated with neighborhood disadvantage or advantage, and that
      relationship seems to vary by race-ethnicity. The varied associations between ICE
      measures and spina bifida by race/ethnicity highlights the importance of using
      targeted interventions in the prevention of spina bifida.

PMID- 30198631
TI  - Porous carbon hosts for lithium-sulfur batteries.
AB  - Lithium-sulfur batteries (LSBs) are considered to be one of the most promising
      alternatives to the current lithium ion batteries (LIBs) to meet the increasing
      demand of energy storage due to their high energy density, natural abundance, low
      cost and environmental-friendliness. Despite great success, LSBs are still
      suffering from several problems including undermined capacity arising from low
      utilization of sulfur, unsatisfactory rate performance and poor cycling life due
      to shuttle effect of polysulfides and poor electrical conductivity of sulfur.
      Under such circumstances, design/fabrication of porous carbon-sulfur composite
      cathodes is regarded as an effective solution to overcome the above problems. In
      this review, we summarize different synthetic methods of porous carbon hosts and
      corresponding integration ways of carbon-sulfur cathodes. We also address the
      pore formation mechanism of porous carbon hosts. The pore size effect on
      electrochemical performance is highlighted and compared. The enhanced mechanism
      of porous carbon host on the sulfur cathode is systematically reviewed and
      revealed. Finally, we demonstrate the combination of porous carbon hosts and high
      profile solid-state electrolytes nowadays, and discuss the challenges to realize
      large-scale commercial application of porous carbon-sulfur cathodes and propose
      their developing trend in the future.

PMID- 30198632
TI  - The past, present, and future of fetal alcohol spectrum disorder work in
      Newfoundland and Labrador: A landscape paper for change.
AB  - OBJECTIVES: In this paper, we provide an overview of best practices in FASD
      prevention, diagnostic, and interventions and supports. In Canada, people
      diagnosed with Fetal Alcohol Spectrum Disorder (FASD) represent a fraction people
      living with FASD. While social stigma may deter people from seeking an FASD
      diagnosis, other deterrents include the lack of screening and diagnostic
      referrals, cost of travelling to a clinic, and lack of clarity of how a diagnosis
      may improve supports and services. Preventing FASD and improving lifelong
      outcomes for people living with FASD requires a coordinated approach between
      prevention, diagnostic, intervention, and support efforts. METHODS: Using the
      example of Newfoundland and Labrador, a province where 60% of the population
      lives in rural communities and benefits from being involved in national
      initiatives and partnerships, we discuss efforts underway in other Canadian
      provinces to address FASD. RESULTS: We make three recommendations that begin to
      address FASD-specific needs in both rural and urban regions: a) a provincial FASD
      consultant position, b) an explicit partnership between provincial government and
      fasdNL, and c) increased access to FASD diagnostic teams. CONCLUSION: While the
      recommendations are both modest and essential first steps, we also suggest that
      collaborations and resource-sharing in FASD prevention and supports are more
      about doing things differently, rather than doing more.

PMID- 30198634
TI  - Labeling Maize (Zea mays L.) Leaves with 15 NH4+ and Monitoring Nitrogen
      Incorporation into Amino Acids by GC/MS Analysis.
AB  - The human body contains approximately 3.2% nitrogen (N), mainly present as
      protein and amino acids. Although N exists at a high concentration (78%) in the
      air, it is not readily available to animals and most plants. Plants are however
      able to take up both nitrate (NO3- ) and ammonium (NH4+ ) ions from the soil and
      convert them to amino acids and proteins, which are excellent sources for all
      animals. Most N is available as the stable isotope 14 N, but a second form, 15 N,
      is present in very low concentrations. 15 N can be detected in extracts of plants
      by gas chromatography followed by mass spectrometry (GC/MS). In this protocol,
      the methods are described for tracing the pathway by which plants are able to
      take up 15 N-labeled nitrate and ammonium and convert them into amino acids and
      proteins. A protocol for extracting and quantifying amino acids and 15 N
      enrichment in maize (Zea mays L.) leaves labeled with 15 NH4+ is described.
      Following amino acid extraction, purification, and separation by GC/MS, a
      calculation of the 15 N enrichment of each amino acid is carried out on a
      relative basis to identify any differences in the dynamics of amino acid
      accumulation. This will allow a study of the impact of genetic modifications or
      mutations on key reactions involved in primary nitrogen and carbon metabolism.
      (c) 2018 by John Wiley & Sons, Inc.

PMID- 30198633
TI  - Outbreak investigations of foot and mouth disease virus in Nepal between 2010 and
      2015 in the context of historical serotype occurrence.
AB  - Foot and Mouth Disease (FMD) is endemic in Nepal and causes substantial economic
      losses in the livestock industry. The goal of this study was to perform an
      epidemiological analysis of FMD outbreaks reported to the Veterinary Epidemiology
      Center, Tripureshwor, Nepal during 2010-2015, in order to strengthen the National
      FMD Control Program. These current data were considered in the context of
      historical data on FMD virus (FMDV) serotypes detected in the country between
      1965 and 2015. During 2010-2015, a total of 1333 livestock holdings reported FMD
      outbreaks in Nepal. On average, 71.2 animals were affected in each outbreak, with
      a case fatality rate of 3.6%. FMD was reported throughout the country, and the
      proportion of affected holdings was not significantly among eco-zones, regions,
      or species. The Hill eco-zone had the highest number of holdings affected (782),
      followed by Mountain (304), and Terai (247). When analysed by the developmental
      region, the Western (381) and Central (368) Developmental Regions had the highest
      numbers of holdings affected. Cattle were the most frequently affected species
      (39%), followed by buffalo (33%), and goats (19%). FMD occurred throughout the
      year, with peaks in winter (December/January) and in the pre-monsoon period
      (April/May). Between 1965 and 2015 FMDV serotype O had the highest prevalence
      (81%), followed by Asia-1 (11%), A (6%), and C (2%). Serotype C was not detected
      after 1996, and only serotype O was reported after 2011. These descriptive
      analyses provide critical landmarks to establish baselines, and document early
      progress of the ongoing Progressive Control Pathway of FMD (PCP-FMD) which could
      be useful in Nepal and other South Asian nations.

PMID- 30198635
TI  - Taxonomic Landscape of the Dark Proteomes: Whole-Proteome Scale Interplay Between
      Structural Darkness, Intrinsic Disorder, and Crystallization Propensity.
AB  - Growth rate of the protein sequence universe dramatically exceeds the speed of
      expansion for the protein structure universe, generating an immense dark proteome
      that includes proteins with unknown structure. A whole-proteome scale analysis of
      5.4 million proteins from 987 proteomes in the three domains of life and viruses
      to systematically dissect an interplay between structural coverage, degree of
      putative intrinsic disorder, and predicted propensity for structure determination
      is performed. It has been found that Archaean and Bacterial proteomes have
      relatively high structural coverage and low amounts of disorder, whereas
      Eukaryotic and Viral proteomes are characterized by a broad spread of structural
      coverage and higher disorder levels. The analysis reveals that dark proteomes
      (i.e., proteomes containing high fractions of proteins with unknown structure)
      have significantly elevated amounts of intrinsic disorder and are predicted to be
      difficult to solve structurally. Although the majority of dark proteomes are of
      viral origin, many dark viral proteomes have at least modest crystallization
      propensity and only a handful of them are enriched in the intrinsic disorder. The
      disorder, structural coverage, and propensity are mapped for structural
      determination onto a novel proteome-level sequence similarity network to analyze
      the interplay of these characteristics in the taxonomic landscape.

PMID- 30198638
TI  - Synthesis of Ethyl-4-ethoxy Pentanoate by Reductive Etherification of Ethyl
      Levulinate in Ethanol on Pd/SiO2 -C Catalysts.
AB  - The synthesis of biomass-derived ethers to be used as biofuels or biofuel
      additives has attracted much attention. Following the recently reported synthesis
      of etherified ester ethyl-4-ethoxy pentanoate (EEP) from gamma-valerolactone
      (GVL) in ethanol catalyzed by H-beta zeolite, an alternative route to prepare EEP
      in high yield has been developed by reductive etherification of ethyl levulinate
      (EL) in ethanol at 140  degrees C under 0.5 MPa H2 with a silica-modified Pd/C
      catalyst. The ether production likely follows a tandem acetalization
      hydrogenolysis process with ethyl-4,4-diethoxy pentanoate (EDEP) as the
      intermediate. The acetalization step can be favored by introducing acidic
      materials, such as SiO2 -carbon or beta zeolite, as a cocatalyst. The combination
      of the Pd/SiO2 -C and beta zeolite mixture leads to 100 % EL conversion and 93 %
      EEP selectivity under optimized reaction conditions. For the first time, the
      standard molar combustion enthalpy of as-prepared EEP is measured by using a
      static oxygen bomb, and the value of which is determined to be about -5658 kJ mol
      1 , which is much larger than that of GVL (-2650 kJ mol-1 ).

PMID- 30198636
TI  - PSTPIP1-associated myeloid-related proteinemia inflammatory syndrome: A rare
      cause of childhood neutropenia associated with systemic inflammation and
      hyperzincemia.
AB  - Neutropenia in pediatric patients can be due to a variety of disorders. We
      describe two patients who underwent extensive evaluation over many years for
      arthralgias and moderate neutropenia of unclear etiology. Genetic testing
      identified a pathogenic variant in PSTPIP1 (proline-serine-threonine phosphatase
      interacting protein 1) in both patients. Markedly elevated inflammatory markers
      and zinc levels confirmed the rare diagnosis of PSTPIP1-associated myeloid
      related proteinemia inflammatory (PAMI) syndrome, tailoring treatment.
      Neutropenia is common in patients with PAMI syndrome. Unique mutations seen in
      PAMI syndrome may account for the specific phenotypic features of this disorder.

PMID- 30198639
TI  - Eruptive hypomelanosis - First case reported outside Asia.

PMID- 30198640
TI  - Active Metabolites from Endolichenic Fungus Talaromyces sp.
AB  - The active metabolites investigation of Talaromyces sp. (strain No. MH551540)
      associated with Xanthoparmelia angustiphylla afforded one new delta-lactone,
      talaromycin A (1), together with six known compounds, clearanol A (2), 6
      methylbiphenyl-3,3',4,5'-tetraol (3), desmethylaltenusin (4), ergone (5),
      ergosterol (6), and palmitic acid (7). The structures of these compounds were
      elucidated by a combination of spectroscopic-data interpretation and single
      crystal X-ray diffraction analysis. The cytotoxicities of 1-7 and the antioxidant
      activities of 3 and 4 were also evaluated.

PMID- 30198637
TI  - Importance of Feedback and Feedforward Loops to Adaptive Immune Response
      Modeling.
AB  - The human adaptive immune system is a very complex network of different types of
      cells, cytokines, and signaling molecules. This complex network makes it
      difficult to understand the system level regulations. To properly explain the
      immune system, it is necessary to explicitly investigate the presence of
      different feedback and feedforward loops (FFLs) and their crosstalks. Considering
      that these loops increase the complexity of the system, the mathematical modeling
      has been proved to be an important tool to explain such complex biological
      systems. This review focuses on these regulatory loops and discusses their
      importance on systems modeling of the immune system.

PMID- 30198641
TI  - [CHRONIC CONTINUOUS NOR-MOBARIC HYPOXIA AUGMENTS CELL TOLERANCE TO ANOXIA(REOXYGE
      NATION: THE ROLE OF PROTEIN KINASES].
AB  - The study evaluated the role of protein kinase C, PI3-kinase and tyrosine kinases
      in the cardi-oprotective effect of the chronic continuous normobaric hypoxia
      (CCNH). Adaptation to CCNH was provided by placing the rats in an atmosphere with
      a low content of O2 (12 %) during 21 days. Anoxia-reoxygenation of isolated
      cardiomyocytes of intact rats caused the deaths of 16.5 % of the cells and the
      lactate dehydrogenase (LDH) release of them. A similar effect on isolated
      cardiomyocytes of adapted rats caused the death of only 6.8 % of the cells and
      less pronounced increase in LDH release. Preincubation of cells for 25 minutes
      with one of the protein kinases inhibitors: che-lerythrine (10 |mM/l); rottlerin
      (1 |j.M/l); genistein (50 |mM/l) eliminated the adaptive increase in cell
      survival and reduction of LDH release. Incubation of cells with PI3-kinase
      blocker wortman-nin (100 nM/l) had no effect on the percentage of cell death of
      adapted animals and LDH release from them after anoxia-reoxygenation. The authors
      believe that the cytoprotective effect of chronic normobaric hypoxia is realized
      through activation of protein kinase C-5 and tyrosine kinases. Kinase PI3 - is
      not involved in the implementation of protective actions CCNH.

PMID- 30198642
TI  - MOFs: New Useful Materials - A Special Issue in Honor of Prof. Susumu Kitagawa.

PMID- 30198643
TI  - Computer-assisted Curie scoring for metaiodobenzylguanidine (MIBG) scans in
      patients with neuroblastoma.
AB  - BACKGROUND: Radiolabeled metaiodobenzylguanidine (MIBG) is sensitive and specific
      for detecting neuroblastoma. The extent of MIBG-avid disease is assessed using
      Curie scores. Although Curie scoring is prognostic in patients with high-risk
      neuroblastoma, there is no standardized method to assess the response of specific
      sites of disease over time. The goal of this study was to develop approaches for
      Curie scoring to facilitate the calculation of scores and comparison of specific
      sites on serial scans. PROCEDURE: We designed three semiautomated methods for
      determining Curie scores, each with increasing degrees of computer assistance.
      Method A was based on visual assessment and tallying of MIBG-avid lesions. For
      method B, scores were tabulated from a schematic that associated anatomic regions
      to MIBG-positive lesions. For method C, an anatomic mesh was used to mark MIBG
      positive lesions with automatic assignment and tallying of scores. Five imaging
      physicians experienced in MIBG interpretation scored 38 scans using each method,
      and the feasibility and utility of the methods were assessed using surveys.
      RESULTS: There was good reliability between methods and observers. The user
      interface methods required 57 to 110 seconds longer than the visual method.
      Imaging physicians indicated that it was useful that methods B and C enabled
      tracking of lesions. Imaging physicians preferred method B to method C because of
      its efficiency. CONCLUSIONS: We demonstrate the feasibility of semiautomated
      approaches for Curie score calculation. Although more time was needed for
      strategies B and C, the ability to track and document individual MIBG-positive
      lesions over time is a strength of these methods.

PMID- 30198644
TI  - Total intravenous anesthesia vs inhaled anesthetic for intraoperative
      visualization during endoscopic sinus surgery: a double blind randomized
      controlled trial.
AB  - BACKGROUND: Bleeding during endoscopic sinus surgery (ESS) can impair
      visualization and delay surgical progress. The role that anesthetic technique may
      have on the quality of surgical field during ESS has been previously studied.
      However, meta-analyses have deemed the current literature inconclusive and
      lacking methodological consistency. This study was designed with these critiques
      in mind to assess the effect of total intravenous anesthesia (TIVA) vs inhaled
      anesthetic on the quality of the surgical field during ESS. METHODS: This study
      was a double-blind, randomized, controlled trial of 30 patients of American
      Society of Anesthesiologists (ASA) class 1 or 2 undergoing bilateral ESS for the
      primary diagnosis of chronic rhinosinusitis. In addition to standard techniques
      to minimize blood loss, study patients were randomized to maintenance anesthesia
      with intravenous propofol or inhaled desflurane. Anesthetic depth was
      standardized using bispectral index (BIS). The primary outcome measured was the
      Wormald grading scale to assess the endoscopic surgical field. RESULTS: The use
      of TIVA was associated with a statistically significant reduction in mean Wormald
      score compared to desflurane (4.21 vs 5.53, p = 0.024). Mean Boezaart score was
      also lower in the TIVA arm (2.18 vs 2.76, p = 0.034). Experimental groups were
      homogeneous in all compared baseline characteristics. Secondary outcomes
      including surgical duration, time to extubation, and estimated blood loss were
      not found to be statistically significant between experimental groups.
      CONCLUSION: Even with all other factors implemented to optimize the surgical
      field, utilization of TIVA vs inhaled anesthetic still resulted in a
      statistically significant improvement in surgical field during ESS.

PMID- 30198645
TI  - Compliance with the "Baby-friendly Hospital Initiative for Neonatal Wards" in 36
      countries.
AB  - In 2012, the Baby-friendly Hospital Initiative for Neonatal Wards (Neo-BFHI)
      began providing recommendations to improve breastfeeding support for preterm and
      ill infants. This cross-sectional survey aimed to measure compliance on a global
      level with the Neo-BFHI's expanded Ten Steps to successful breastfeeding and
      three Guiding Principles in neonatal wards. In 2017, the Neo-BFHI Self-Assessment
      questionnaire was used in 15 languages to collect data from neonatal wards of all
      levels of care. Answers were summarized into compliance scores ranging from 0 to
      100 at the ward, country, and international levels. A total of 917 neonatal wards
      from 36 low-, middle-, and high-income countries from all continents
      participated. The median international overall score was 77, and median country
      overall scores ranged from 52 to 91. Guiding Principle 1 (respect for mothers),
      Step 5 (breastfeeding initiation and support), and Step 6 (human milk use) had
      the highest scores, 100, 88, and 88, respectively. Step 3 (antenatal information)
      and Step 7 (rooming-in) had the lowest scores, 63 and 67, respectively. High
      income countries had significantly higher scores for Guiding Principles 2 (family
      centered care), Step 4 (skin-to-skin contact), and Step 5. Neonatal wards in
      hospitals ever-designated Baby-friendly had significantly higher scores than
      those never designated. Sixty percent of managers stated they would like to
      obtain Neo-BFHI designation. Currently, Neo-BFHI recommendations are partly
      implemented in many countries. The high number of participating wards indicates
      international readiness to expand Baby-friendly standards to neonatal settings.
      Hospitals and governments should increase their efforts to better support
      breastfeeding in neonatal wards.

PMID- 30198646
TI  - Mortality factors in infants with congenital diaphragmatic hernia: A systematic
      review.
AB  - BACKGROUND: Congenital diaphragmatic hernia (CDH) is a malformation of the
      diaphragm accounting for 8% of all major congenital anomalies. Although many
      clinical factors of survival in children with CDH have been established, limited
      research exists on the role of sociodemographic and other factors. We aimed to
      systematically identify and summarize all available international literature,
      published from January 2000 to July 2017, evaluating specific mortality factors
      for children with prenatally diagnosed, isolated, left-sided CDH. METHODS:
      MEDLINE, PROSPERO, EMBASE, Scopus, The Cochrane Library databases, and the table
      of contents for the past 5 years for relevant journals were searched
      systematically. The risk factors of interest were as follows: birth weight,
      gestational age (GA) at diagnosis, GA at birth, infant sex, maternal age,
      ethnicity, socioeconomic status (SES), and plurality. The primary outcome measure
      was survival. Data were extracted on study design, study quality, participant
      data, and survival-related effect estimates. RESULTS: Seven studies fulfilled the
      inclusion criteria. In total, 347 children were included in the review. Birth
      weight, GA at diagnosis, and GA at birth were evaluated in five studies each,
      infant sex in two, and maternal age in one. None of these factors were
      significantly associated with survival. No studies evaluated the influence of
      plurality, ethnicity or SES. CONCLUSION: Although the factors of interest showed
      no significant association with survival, more evidence is required to confirm
      these findings. Understanding whether sociodemographic factors are associated
      with survival may help inform the development of public health interventions to
      improve survival rates for children with CDH.

PMID- 30198647
TI  - Illuminating Mexican Migrant Adolescents' Dental Access and Utilization
      Experiences.
AB  - OBJECTIVE: To illuminate Mexican migrant adolescents' dental access and
      utilization experiences. RESEARCH DESIGN: Qualitative focus groups were conducted
      in English between July 2015 and March 2016 as part of a community-based
      participatory research project. PARTICIPANTS: Adolescents (n=61) aged 12-19
      years, from Mexican migrant worker families, who sought healthcare services at a
      federally-qualified migrant health clinic in San Diego County, California.
      METHOD: Seven focus groups, with different sessions for 12-14, 15-16, and 17-19
      year olds. Group size ranged from 4-14. Groups were audio-recorded, transcribed
      verbatim, then analyzed using content and general thematic analyses by two
      researchers using Dedoose qualitative analysis software. Analysis was guided by
      the Behavioral Model for Vulnerable Populations. RESULTS: Multiple themes
      emerged: dental fear, difficulty with scheduling dental appointments, competing
      with family demands, family income and dental tourism, home remedies, lack of
      direct adolescent-provider communication, and negative dental visit experiences.
      Adolescents expressed high levels of dental fear and expressed negative dental
      visit experiences. Cost was a top barrier to care, despite most having dental
      insurance. Some described seeking dental services and braces in Mexico due to
      cost. Adolescents wanted providers to discuss their oral health and treatment
      needs with them directly as patients, rather than with their parents. CONCLUSION:
      Adolescents identified structural and communication barriers that impede access
      to dental care. Improved patient-provider communication may help build rapport,
      mitigate dental fear, and facilitate adolescents' understanding of needed dental
      treatment and their oral health status. Dental providers may benefit from
      training to enhance culturally competent communication with Mexican migrant
      adolescents, and should discuss treatment plans with adolescent patients
      directly.

PMID- 30198648
TI  - [Research on the Distribution of Gas Concentration of Two-Dimensional
      Reconstruction Based on Tunable Diode Laser Absorption Spectroscopy with
      Multispectral Absorption].
AB  - The two-dimensional concentration distribution was reconstructed by using
      algebraic iterative reconstruction algorithm. This paper mainly focused on the
      effects of multispectral H2O absorptions on condition that the laser beam was
      less and the temperature was known, i.e. the influence of temperature on spectral
      line-strength was not considered as to this concentration distribution. Based on
      ART algorithm, increased spectral lines and increased laser beam were compared
      under the same concentration model. Three H2O lines were selected to reconstruct
      two-dimensional distribution of non-uniform gas concentration, and these three
      transitions were selected within the external cavity diode laser turning range in
      the simulated system. The interested region was discretized to 10*10 grid points,
      and the temperature and concentration of the reconstruction model were not evenly
      distributed, so the unimodal distribution and bimodal distribution were used to
      describe the concentration distribution. The simulated system also calculated the
      effective utilization of laser beams and absorption lines. The results showed
      that the reconstruction quality quickly increased with increasing H2O absorption
      lines when the laser beams were very few, the increased absorption lines could
      get more spectral information related to the concentration. The increased laser
      beam is also effective to improve the accuracy of reconstruction results, but
      increasing the absorption lines can better reconstruct a two-dimensional
      concentration distribution. Improving the absorption lines can also effectively
      reduce the costs of the hardware and the complexity of the measurement system,
      which shows that the multispectral absorption lines are applicable to in-situ
      measurements.

PMID- 30198650
TI  - [ESTIMATION OF THE EFFECTS OF GEOMAGNETIC AND SOLAR ACTIVITY ON THE HUMAN BRAIN
      BIOELECTRICAL PROCESSES WITH STRUCTURAL FUNCTION].
AB  - We investigate the impacts of sharp variations in solar and geomagnetic activity
      (GMA) at high latitudes on the human brain bioelectrical activity by means of the
      empirical structure function of multi-channel EEG. Ten healthy men ages 19 to 37
      took part in the study. EEG was recor- ded daily over the 25 days test period
      that was marked by C- and M-class solar flares and geomagnetic storm levels in
      the G2-G3 range. The EEG signals were used for the estimate of the mul-tivariate
      temporal structure function (SF) of the first order in 8-dimensional space. The
      value of the SF correlation radius is used here as an estimation of a scale of
      the integral temporal correlation structure of multi-channel EEG, while the value
      of the SF horizontal asymptote is used as an estimation of the spatial
      correlation structure of EEG. It is shown that GMA variations make an even
      greater impact on the SF correlation radius, than on the SF asymptote. We reveal
      the disturbing and modulating effects of geomagnetic and solar activity on the SF
      parameters and its power spectrum. Thus, the SF of multi-channel EEG allows us to
      estimate the effects of heliogeophysical factors on the integrated brain reaction
      as a unitary system and may be used to investigate the environmental influence on
      the humans.

PMID- 30198649
TI  - [INVOLVEMENT OF r38 MARK OF SENSORY NEURONS IN OUABAIN-ACTIVATED SIGNALING
      CASCADE].
AB  - Recent investigations of the new transducting function of Na+,K+-ATPase is of
      great interest. Na+,K+-ATPase might be a target (receptor) for cardiotonic
      steroids. This membrane protein switches on intracellular signaling mechanisms
      due to its ligand-receptor interactions with the steroids that, in turn, result
      in activation of intracellular cascade processes. r38 belongs to mito-gen
      activated protein kinase family (MAPK). The kinase transduces signals of wide
      range intra-cellular signaling cascades that control proliferation,
      differentiation, and survival. Using embryonic organotypic tissue culture method
      the present work shows that r38 MARK is involved in the signal transducting
      process in series with Na+,K+-ATPase.

PMID- 30198652
TI  - [REACTIVITY AND RESISTANCE OF THE SPINAL STRUCTURES WHEN PERFORMING INSTRUMENTAL
      CORRECTION OF SPINAL DEFORMITIES].
AB  - The aim of the study was the electroneuromyographic evaluation of the spinal cord
      pyramidal structures reactivity and resistance in response to the impact of
      intraoperative factors associated with the application of technologies
      instrumental correction of spinal deformities of various etiologies and degrees
      of severity, realized with the help of submersible transpedicular fixation
      systems. Before treatment and 4-31 (9.6 +/- 0.3) days after surgery using methods
      of global and stimulation (M-responses) electroneuromyography were examined 135
      patients 8-50 (16.4 +/- 0.6) years (42 male, 93 female) with spinal deformities
      of various etiologies and severity. The intrao perative maximum angle correction
      of the spinal column ranged from 3 degrees  to 95 degrees  (37.2 +/- 1.5 degrees
      ). To assess the reactivity of the spinal cord structures located at the top of
      the primary arc deformation used integral index - the index of sensorimotor
      deficit (ISD). The lowest values of ISD and most distinct postoperative negative
      trends of this indicator were observed in persons with spinal deformities of
      neuromuscular etiology.

PMID- 30198651
TI  - [Research on Radiation Spectrum of Pulverized Coal Combustion Flame].
AB  - In order to study on radiation spectrum of pulverized coal flame, radiation
      spectrums of pulverized coal flame on flat flame burner were measured with fiber
      optic spectrometer and the radiation characteristic was analyzed in detail.
      Distribution curves of radiation intensity of flame with wavelength were obtained
      based on Planck's Law and calibration by using blackbody furnace. Then,
      combustion parameters such as temperature and emissivity were calculated by using
      least square method. Therefore, the measurement method based on radiation
      spectrum of pulverized coal flame was proposed. And the experimental
      investigations on pulverized coal flame under different conditions were carried
      out with this method. The result shows that the radiation spectrum of pulverized
      coal flame is significant and continuous in the wavelength ranging from 200 to 1
      100 nm. The temperature and emissivity of flame can be determined by using
      Planck's Law and least square method. Meanwhile, emission peaks of alkali metal
      such as sodium and potassium appear on the radiation spectrum of pulverized coal
      combustion flame near 590, 766, 769 and 779 nm, and the appearance of these
      emission lines is related with temperature. When the concentration of pulverized
      coal is increasing, the temperature of pulverized coal flame has a little change
      but the emissivity changes obviously. The intensity of radiation is increasing
      greatly with emissivity. It can provide important reference for combustion
      optimization of boiler.

PMID- 30198653
TI  - [Laser Induced Time-Resolved Fluorescence Spectroscopy Characteristics of
      Fluoranthene in Ethanol with Eanosecond Laser of 355 nm].
AB  - Polycyclic Aromatic Hydrocarbons (PAHs) have been widely investigated in
      environmental field, for most of them are mutagenic (carcinogenic, teratogenic,
      mutagenic). The influence of delay time and gate width on the time-resolved
      fluorescence spectroscopy of fluoranthene in ethanol was studied in this paper.
      Furthermore, laser induced time-resolved fluorescence spectroscopy of
      fluoranthene with different concentration were also researched. According to the
      results, fluorescence kinetics decay curves and fluorescence lifetime of
      fluoranthene matched. The research results showed that there was closely
      relationship between the fluorescence spectrum of fluoranthene and the delay time
      and gate width of detector. When the delay time was fixed, the fluorescence
      intensity of fluoranthene grew increased as the gate width increased. When the
      gate width was fixed, the fluorescence intensity of fluoranthene increased first
      and then decreased with the delay time increases. The process of the attenuation
      of fluorescence intensity of fluoranthene with time delay conformed to the
      exponential decay process. The stepwise dilution of fluoranthene ethanol solution
      was also studied. With increasing dilution, the fitting of fluoranthene
      fluorescence lifetime increased. The results of this paper can provide a
      technical basis for the detection of PAHs in the environment, due to the
      different characteristics of the fluorescent substance having fluorescence
      lifetime.

PMID- 30198654
TI  - [Online Detection System on Acetylene with Tunable Diode Laser Absorption
      Spectroscopy Method].
AB  - Based on tunable diode laser absorption spectroscopy (TDLAS) technique, an
      acetylene (C2H2) online detection system was developed by using the absorption
      band at the wavelength of 1.534 MUm of C2H2 molecule. The sensing system consists
      of four modules including a distributed feedback (DFB) laser, a DFB laser driver,
      a gas cell with single optical path and a data processing module. With the
      prepared standard C2H2 gas sample, detailed measurements were carried out to
      study the detection performance of the system. Experimental results reveal that,
      the limit of the system (LOD) is about 0.02%; a good linear relationship is
      observed between C2H2 gas concentration and the amplitude of the 2f signal is
      within the range of 0.02%~1%. A long-term measurement lasting for 20 h on a 0.5%
      C2H2 gas sample was carried out to test the stability of the system. Compared
      with the C2H2 detection systems utilizing quantum cascaded lasers (QCLs) and
      wideband incandescence, this system has great advantage due to the capability of
      using long-distance and low-loss optical fiber for remote monitoring. With self
      developed DFB laser driver and lock-in amplifier, the system has good prospects
      in industrial field because of its simple structure, low price and capability of
      easy to be integrated.

PMID- 30198656
TI  - [Study on the Design of Explosive (HNS) Content Analysis System Based on THz
      Spectrum Monomer].
AB  - HNS quantitative spectral analysis can not be achieved with the existing infrared
      Fourier transform spectrometer. As a common monomer explosive concerned, quick
      identification and quantitative analysis of the substance is important, so it is
      necessary to research and design a HNS detection system based on THz
      spectroscopy. Transmissive mode was used in the system to calculate the content
      of HNS. Electro-optic modulator module was introduced in the system, in order to
      achieve steady and rapid static scanning optical path. In the experiments HNS
      characteristic absorption peak positions were acquired. With this basis, combined
      air absorption characteristics of the wavelength band and spectrum data
      correlation expression was obtained, thus more characteristic wavelengths
      selected were determined. According to Beer-Lambert law, the function expression
      of HNS content and coefficient formula were presented. In the experiment
      different content of HNS sample powder was obtained with chemical configuration
      method with the content at the standard level. It made HNS sample powder into HNS
      Sample slice for all HNS samples, and it carried out HNS content testing with
      MINI-Z Terahertz spectroscopy and the system. Experimental results show that the
      results of the two methods are similar in the range of 0.10% to 50.00% for HNS
      content. Their error is less than 5.0% compared to the standard value, and the
      system has better linearity.

PMID- 30198655
TI  - HYPOXIA AND GLYCOLYSIS AS FACTORS DETERMINING THE MALIGNANT PHENOTYPE.
AB  - The review deals with the role of hypoxia and glycolysis in the development of
      cancer. Experimental resultsdemonstrate that the function of glycolysis in tumour
      cells is not limited to providing energy. Glycolysisstimulates the activity of
      transcription factor HIF1a. HIF1a in complex with protein ARNT stimulates
      expressionof numerous genes. There are genes encoding proteins of glycolysis,
      telomerase, P-glycoproteins, antiapoptoticproteins belonging to bcl2 family,
      inhibitor of pyruvate dehydrogenase-pyruvate dehydrogenase
      kynase,dedifferentiation genes and others. Inhibition of mitochondria respiratory
      chain by inhibiting of pyruvatedehydrogenase stimulates accumulation of pyruvate
      in the cell. Lactate dehydrogenase transforms pyruvate onlactate. Accumulation of
      lactate in tumour cells activates monocarboxylate transporter. As a result,
      lactate andproton are displayed in the intercellular space. There is a drop in
      the pH in tumour tissue. The low pH promotesthe activity of various proteases
      that degrade intercellular matrix. The enhancement of invasion is observed
      intumours area with low pH level. The restoration of normal pH level in tumour
      tissue inhibits invasion and metastasis.Thus, it is possible to conclude that
      hypoxia is a physiological state of cells that stimulates and mantainestumour
      process. Aerobic glycolisis (Warburg effect) stimulates tumour growth even in the
      case of sufficientoxygenation of the cells. Modern views on the mechanism of the
      Warburg effect is given. The possibility ofusing inhibitors of different stages
      of glycolysis as mono anticancer agents or in combination with
      conventionalanticancer compounds is discussed.

PMID- 30198657
TI  - DERIVATION AND CHARACTERISTICS OF THE NEW SUBLINE OF HUMAN EMBRYONIC STEM CELLS
      SC6-FF IN ALLOGENIC FEEDER-FREE CULTURE SYSTEM.
AB  - A new human embryonic stem cell subline SC6-FF has been derived from SC6 cells in
      allogenic feeder-free culture system. Extracellular matrix proteins and
      conditioned medium from mesenchymal stem cellline SC6-MSC were the key components
      of the feeder-free culture system that therefore was allogenic forSC6-FF cells.
      SC6-FF subline has underwent more than 100 cell population doublings and retained
      normal diploidhuman karyotype: 46, XX. The average doubling time of the cell
      population was 23.7 +/- 0.8 h that does notdiffer from that for the parent SC6
      line. The presence of undifferentiated hESCs markers, alkaline
      phosphataseactivity, Oct-4, SSEA-4 and TRA-1-60, has been verified by
      histochemical and immunofluorescence analysis.Non-directional differentiation of
      SC6-FF subline has led to development of cells that differ in size and
      morphologyfrom the cells in the parent population. These cells demonstrate the
      ability of differentiation in the derivatesof three germ layers by expressing the
      characteristic markers of the ectoderm (alpha-fetoprotein), mesoderm(a-actinin)
      and endoderm (a-fetoprotein) cells. We can conclude that the obtained
      characteristics of thenew feeder-free SC6-FF sub-line correspond to the status of
      the human embryonic stem cells.

PMID- 30198658
TI  - THE INFLUENCE OF QUERCETIN ON THE HEPATIC DIFFERENTIATION OF HUMAN ADIPOSE
      DERIVED MESENCHYMAL STEM CELLS.
AB  - The human adipose-derived mesenchymal stem cells was shown to be hepatic
      differentiated under influenceof inductor factors. The differentiation of MSCs
      was induced by fibroblast growth factor-4, hepatocytegrowth factor, oncostatin M
      and dexamethasone. The influence of quercetin on the hepatic differentiation
      ofMSCs in culture was investigated. The adding quercetin into induction medium (1
      or 10 mmol/l) enhanced themanifestation of signs of hepatic differentiation MSCs
      such as urea secretion, cytokeratin 19 and a-fetoproteinsynthesis. Quercetin
      modulating action on the CYP1A - cytochrome P450 activity in differentiated cells
      wasfound. MSCs which was differentiated in the presence of quercetin had a higher
      viability and resistance to oxidativestress.

PMID- 30198659
TI  - [Infrared Spectroscopy Combined with Chemometrics for Rapid Discrimination on
      Species of Bolete Mushrooms and an Analysis of Total Mercury].
AB  - Fourier transform infrared spectroscopy combined with chemometrics was used to
      establish a method for rapid identification of different species of bolete
      mushrooms and determination of total mercury (Hg). In this study, 15 species of
      bolete mushrooms were used and the information of infrared spectra of 48 samples
      was collected. Meanwhile, the total Hg was determined with cold-vapour atomic
      absorption spectroscopy and direct mercury analyzer. The food safety of bolete
      mushrooms was evaluated according to provisional tolerable weekly intake (PTWI)
      for Hg recommended by the United Nations food and agriculture organization and
      the World Health Organization (FAO/WHO). The original infrared spectra were
      optimized with Norris smooth, multiplicative signal correction (MSC), second
      derivative, orthogonal signal correction and wavelet compression (OSCW). The
      spectra data were analyzed with principal component analysis (PCA) and partial
      least squares discriminant analysis (PLS-DA) after the optimal pretreatment. Then
      the discrimination model for different species of bolete mushrooms and prediction
      model of Hg content were established, respectively. The results showed that: (1)
      The cumulative contribution of first three principal components of PCA was 77.1%.
      Different species of boletes can be obviously distinguished in principal
      component score plot. It indicated that the chemical composition or contents were
      different in these species of boletes. (2) There were significant differences in
      total Hg contents in different samples and the total Hg content in the boletes
      were 0.17~15.2 mg.kg-1 dry weight (dw). If adults (60 kg) ate 300 g fresh bolete
      mushrooms a week, Hg intakes in a few samples were higher than the PTWI standard
      with potential risks. (3) The infrared spectra data in combination with the total
      Hg content was performed by partial least squares discriminant analysis. The
      mushroom samples with low (<=1.95 mg.kg-1 dw), medium (2.05~3.9 mg.kg-1 dw) and
      high (>=4.1 mg.kg-1 dw) total Hg content could be discriminated. Moreover, the
      more different the Hg content was, the more easily to distinguish. In addition,
      the prediction model of total Hg content of boletes was established. The R2 and
      RMSEE of the training set were 0.911 4 and 1.09, respectively while R2 and RMSEP
      of validation set were 0.949 7 and 0.669 5, respectively. The predictive values
      of total Hg content in boletes were approximate to the measured values which
      showed that the model has good predictive effect. Infrared spectroscopy combined
      with chemometrics can be used for rapid identification of bolete species and
      discrimination of bolete samples with different contents of total Hg.
      Furthermore, the total Hg content could also be predicted, accurately. This study
      may provide a rapid and simple method for quality control and edible safety
      assessment of wild-grown bolete mushrooms.

PMID- 30198660
TI  - [Structural Analysis of Organic Matter Composition in Piggery Wastewater during
      the Process of Organic Degradation Based on FTIR Spectroscopy].
AB  - More and more attentions were paid on the environmental pollutions of wastewater
      discharged from scale pig farms, and it could provide scientific bases for
      formulating reasonable pollution control measures to study the structural changes
      of organic matter composition in piggery wastewater. In the present study, a
      laboratory-scale incubation experiment was carried out with piggery wastewater
      collected from different scale pig farms, and a continuous sampling was conducted
      at a certain interval during the process of incubation experiment. The main
      purpose of this study was to elucidate the change of structural composition of
      dissolved organic matter (DOM) in piggery wastewater during the process of
      organic degradation. All dried and solid DOM samples were achieved using
      filtration and freeze-drying methods. Spectral analysis of all DOM samples was
      completed with the application of Fourier transform infrared (FTIR) spectrometer.
      Results of spectral analysis showed a similar DOM structural composition was
      observed in the wastewater derived from different scale pig farms, and was mainly
      comprised of lipids, proteins, fulvic acids, polysaccharides, and phenolic
      compounds. With the increase in the incubation days, the percent of functional
      groups, related to proteins, phenolic acids, and lipids, decreased gradually and
      kept stable eventually, while these functional groups, linked with fulvic acids
      and polysaccharides, showed a significant increase and leveled off at the end.
      Compared with primary samples, fulvic acids and polysaccharides were the
      predominant fractions of DOM at 20 days after organic degradation, indicating a
      higher aromatic degree of DOM. Meanwhile, the degradation rate of OH bonded by
      intermolecular H-bond of cellulose was faster than OH bonded by intra-molecular H
      bond of cellulose, whereas the latter was more sensitive to microbial
      degradation. The degradation rate of phenolic hydroxyl C-O was the fastest,
      followed by aromatic COOH, carbohydrate C-O, and amide CO. Furthermore, the
      carbohydrate C-O was apt to be utilized preferentially by microorganisms. In sum,
      the structural change of various DOM in piggery wastewater was different during
      the process of organic degradation.

PMID- 30198661
TI  - MARKERS OF THE PROSTATE BASAL LAYER CELLS ARE EFFECTIVE INDICATORS OF ITS
      MALIGNANT TRANSFORMATION.
AB  - Development of local or general forms of prostate cancer (PC) depends on
      formation of metastasis the biologicalnature of which is based on epithelial
      mesenchymal transition (EMT). AIO presents highly conservativereversible program
      that is maintained by specific transcription factors which suppress E-cadherin
      expressionand support production of mesenchymal polarity factors. The goal of
      this work was to study the functionallydistinct markers in malignant prostate
      tissue of patients with prostate cancer using the histological evaluation,reverse
      polymerase chain reaction and immunobloting. Our results showed that mostly
      evident alterations inprostate tissue of patients with prostate cancer were
      associated with the cells of basal layer. Expression levels ofthe markers of this
      layer: A-cadherin and NK5, were decreased, while that of AMACR - increased. These
      resultssupport an idea that the basal cells are primarily targeted during
      transformation and acquired the luminalphenotype in the course of the following
      differentiation. The functional analysis of these results may be performedin
      future using selected prostate cancer stem cells.

PMID- 30198662
TI  - [Study on Outliers Influence in NIR Quantitative Analysis Model].
AB  - As a secondary analysis method, reproducibility and reliability of near-infrared
      spectroscopy (NIRS) quantitative analysis are quite dependent on modelling
      process. In this paper, it is focused on outlier analysis for protein
      quantitative model of wheat based on NIRS. The purpose is to discuss the outlier
      effect in modelling process of complex sample set. The indicator of outliers is
      the deviation between two interpretative percentage curves in partial least
      squares regression (PLSR) modelling, when two percentage curves have significant
      deviation or departure point, the sample set should include the outliers. The
      innovative research work is the analysis and treatment of outliers. On the basis
      of sub-model ergodic calculation method, outliers can be gradually identified and
      picked-up. The standard deviation of model's prediction residual is used as the
      reference graduation to distinguish the degree of deviation. According to the
      degree of deviation from sample population, outliers can also be divided into
      significant outliers, relative outliers and potential outliers. In this paper,
      the significant outliers of the sample set are about 7.8%, and the relative
      outliers are about 15.6%. The outliers will pull normal samples apart from the
      ideal fitting line and make the dispersity increase. No matter modelling with
      removed outliers or weighted samples, the purpose is to make the fitting results
      of quantitative analysis modelling more inclined to majority samples, while
      reducing or eliminating the impact of outliers.

PMID- 30198663
TI  - [Study on Identification of PBDEs and Characteristic Information Extraction of
      Biological Toxicity Based on Infrared Spectrum Partition].
AB  - In this paper, 9 most abundant PBDE congeners in environment and 14 congeners
      with high/medium biological toxicity were selected as target compounds. Firstly,
      IR spectra of 23 compounds were divided into 6 spectrum regions based on known
      vibrational assignment, and their identification abilities for PBDEs were
      evaluated by using similarity analysis. Then, the spectrum regions with high
      identification ability relatively have been analyzed to search identification
      method on the basis of each spectrum characteristic. At last, the principal
      component analysis and discriminant analysis method were used to extract
      characteristic spectrum information of congeners with high/medium biological
      toxicity and establish biological toxicity discriminant model. The triangle
      breathing vibration region (961~1 153 cm-1) and C-O stretching vibration region
      (1 153~1 346 cm-1) has been filtered as characteristic IR spectrum regions
      because of smaller similarity among PBDEs relatively. For the former, the
      information of vibration peaks distribution can be taken as tool to
      identification, with the smallest frequency difference of 3.19 cm-1 among 23
      congeners and bad ability to distinguish PBDEs from dioxin-similar compounds. For
      the later, the frequency and shape of main peak is as mark and the smallest
      frequency difference among PBDEs and between PBDEs with dioxin-similar compounds
      are 0.74 and 0.67 cm-1 separately, both larger than the common minimum resolution
      of IR spectrum 0.5 cm-1, depicting good ability for both inner and outer
      identification of PBDEs. The established biological toxicity discriminant model
      via discriminant analysis also have shown well ability to biological toxicity
      prediction, with accuracy of 100% and 88.9% for high/medium and low biological
      toxicity relatively, representing the extracted IR spectrum information from
      congeners with high/medium toxicity can realize the accurate classification of
      biological toxicity for PBDEs.

PMID- 30198664
TI  - CHANGES IN THE NUMBER OF NEURONS, ASTROCYTES AND MICROGLIA IN THE BRAIN AFTER
      ISCHEMIC STROKE ASSESSED BY IMMUNOHISTOCHEMISTRY AND IMMUNOBLOTTING.
AB  - It is known that the mechanisms of damage in the brain after stroke are regulated
      by combination of severaltypes of cells, primarily of neurons, astrocytes,
      endothelium and microglia. Ischemic exposure disrupts thebalance in the cellular
      composition of the brain; in the lesion, cells die by necrosis while in tissue
      surrounding ischemic zone the delayed induction of apoptosis occurs, and namely
      the ratio of death of different cells determinesthe clinical outcome of the
      disease. Thus, the assessment of death of various cell types of the
      neurovascularunit is an important part of fundamental studies of the mechanisms
      of brain damage and pre-clinical studiesof potential neuroprotective drugs. In
      this line, we have conducted a comparative study of the two most oftenused
      methods: immunohistochemical staining of brain sections, allowing to determine
      the number and localizationof specific cells in the tissue among other types of
      cells, and immunoblotting that detects specific proteinsin the tissue homogenate.
      We have found that, depending on the type of cells, changes in their number and
      compositionafter stroke can be diffuse or localized, which imposes restrictions
      on the use of any method of estimationof the number of cells in brain tissue. In
      general, the most preferable is the use of immunohistochemistry,however, with
      certain limitations, immunoblotting can be used in estimating amounts of
      astroglia and microglia.

PMID- 30198665
TI  - [Discrimination of Varieties of Cabbage with Near Infrared Spectra Based on
      Principal Component Analysis and Successive Projections Algorithm].
AB  - The varieties of cabbage seeds directly affect the yield and quality of cabbage,
      in order to rapidly and nondestructively identify the varieties of cabbage seeds,
      near infrared spectra technique were applied in this study and reflectance
      spectrum of the cabbage seeds was obtained. Firstly, to excavate the effective
      information in the spectral data and improve signal to noise ratio, the raw
      spectra was pre-processed with the method of standard normal variate (SNV) and
      multiplicative scatter correction (MSC). Secondly, principal component analysis
      (PCA) was used to analyze the clustering of cabbage samples, then the
      characteristic differentia of three cabbage varieties was obtained through
      qualitative analysis. Six Effective wavelengths were selected by successive
      projections algorithm (SPA). Finally, the full spectra variable, the first three
      principal components (PCs) using PCA and selected effective wavelengths using SPA
      were respectively set as inputs of the partial least squares discriminant
      analysis (PLS-DA) and least-squares support vector machine (LS-SVM) models for
      the classification of cabbage seeds. As can be seen from the two dimensional plot
      drawn with the scores of PC1 and PC2 (the first two principle components), PC1
      and PC2 had a good clustering effect for different kinds of cabbage seeds. LS-SVM
      models performed better than PLS-DA models, the correct rates of discrimination
      were 100% achieved with LS-SVM models. PLS-DA and LS-SVM models built based on
      the selected wavelengths performed better than the models built based on the
      first three principal components, moreover, the SPA-LS-SVM model obtained the
      best results among all models, with 100% discrimination accuracy for both the
      calibration set and the prediction set. The overall results show that SPA can
      extract wavelengths, and the LS-SVM model combined with SPA can obtain optimal
      classification results. So the present paper could offer an alternate approach
      for the rapid discrimination of cabbage seeds variety.

PMID- 30198666
TI  - IMMUNOPHENOTYPICAL CHARACTERISTICS OF CELLULAR COMPOSITION IN BREAST MILK.
AB  - The morphology and immunophenotype of female colostrum adherent cells with the
      help of CD3, CD31,CD34, CD45, CD68, vimentin, and osteocalcin antibodies panel
      was studied in short-term (6-7 days) culturein vitro. Approximately equal (1 : 1)
      ratio of fibroblast-like and rounded cells was observed in 20 % of
      culturalflasks. The cells with regular shape mixed with single fibroblasts were
      noted in 80 % of cultural flasks. Thediameter of spreaded cells varied within 10
      100 mm. All cells adhered to plastics did not express CD3 andinteracted slightly
      (sl) with antibodies to CD31, CD34, and CD45. At the same time, adherent cells
      with intensiveCD68, vimentin and osteocalcin staining have been revealed.
      Literature data allows to interpretCD68+CD3-CD31slCD34slCD45sl immunophenotype of
      significant part of mother colostrum adherent cells asbelonging to monocyte
      macrophage lineage. Marked expression of stromal antigens (vimentin, osteocalcin)
      in40-45 % adherent cells in cultural medium without osteogenic supplements (beta
      glycerophosphate, ascorbicacid, dexamethasone) proposes an existence of
      osteoblasts fraction differentiated in colostrum from mesenchymalstem cells under
      an action of breast milk humoral factors.

PMID- 30198667
TI  - [Effects of Freezing and Thawing Treatments on Beef Protein Secondary Structure
      Analyzed with ATR-FTIR].
AB  - In order to further clarify the influence mechanism of different freezing
      temperature on meat quality in meat industry. The effects of freezing at -18, -23
      and -38 C on the stability of protein secondary structures of beef were studied.
      The attenuated total reflectance Fourier transfer infrared spectroscopy(ATR
      FTIR)technique and automatic deconvolution, curve fitting and other calculation
      and analysis methods were used to analyze the changes of beef myofibrillar
      protein infrared spectra and secondary structures during -18, -23 and -38 C
      freezing-thawing processes. ATR-FTIR results showed that the peak high and peak
      area of infrared spectra of beef myofibrillar protein in the freezing-thawing
      processes were changed, and the red shift or blue shift of wavenumbers occurred.
      The intensities of the absorption peak of 3 500~3 300 cm-1 in the infrared
      spectra of the frozen-thawed beef were reduced or even disappeared. This
      indicated that the intramolecular and intermolecular hydrogen bonding
      interactions, which formed by the bound water O-H group and the amino acid CO
      group, in thawed beef myofibrillar protein were broken. In other words, freezing
      can result in the destruction of beef myofibrillar protein secondary structures
      and protein advanced structures unfolded. Once the beef is thawed, the unfolded
      protein would reaggregation, and protein renaturation. Freezing could affect the
      stability of beef myofibrillar protein, the relative content of alpha-helix, beta
      sheet, and beta-turn of beef myofibrillar protein were decreased, and the alpha
      helix and ordered structures changed to the randon coil and disordered
      structures. After thawing, the increase of beta-sheet relative content of beef
      myofibrillar protein at -38 C was greater than that of -23 and -18 C. The
      stability of -38 C frozen beef myofibrillar protein was the best, and the protein
      renaturation was also the best after thawing. That is, the lower the freezing
      temperature, the lower the measure of freezing denaturation of beef myofibrillar
      protein, and the better the secondary structures stability of beef myofibrillar
      protein. The experimental study based on the actual production condition of the
      meat industry. And the effect of freezing temperatures on beef protein
      denaturation and the possible mechanism were revealed at the micro-aspect. It can
      be seen that the ATR-FTIR technology can reflect the changes of protein secondary
      structures in the process of freezing-thawing of beef, and reveal the regularity
      of beef protein denaturation, which can be used to identify and evaluate the
      quality of frozen meat. The experimental results provide a reference for the
      freezing preservation process and a method for the quality evaluation of meat.

PMID- 30198668
TI  - [Determination of Wine Varieties with NIR and Fusion of Multiple Classifiers].
AB  - The conventional qualitative analysis of near infrared spectroscopy (NIR)
      commonly uses one single classification model. This paper focused on the fusion
      of multiple classifiers based on different single classifiers by using the fused
      classifier to determine different varieties of red-wines. NIR spectra of 170 red
      wine samples were collected by using Fourier transform near-infrared
      spectrometer. Red-wine classification models were established respectively, based
      on PLS-DA, SVM, Fisher and Ada-Boost. Then these models were selected to obtain
      some different base classifiers according to Diversity Measure Feature Selective
      (DMFS). The highest accuracy rate of determining different varieties of red-wine
      test samples of four single base classifiers was up to 88.24%, and at the same
      time the lowest discriminant accuracy rate was 81.18%. At last, we got the fused
      classifier, which combined four base classifiers with weighted voting principle,
      and determined its test set again by using the fused classifier. The final
      classification accuracy rate for red-wine varieties increased to 92.94%, In
      contrast with one single classifier, the lowest misjudged number of fused
      classifiers decreased from 9 to 6.These results suggested that the performance of
      fused classifier is superior to one single classifier. It is feasible to use
      fused classifier combined with near infrared spectroscopy to determine different
      varieties of red-wines.

PMID- 30198669
TI  - A METHOD FOR THE QUANTITATIVE ASSESSMENT OF NUCLEAR ERYTHROCYTES SHAPE.
AB  - It is generally accepted that nuclear erythrocytes of some vertebrates are shaped
      like ellipses. Nevertheless,the formal proof for this has not been presented.
      Here, the experimental data and theoretical calculations arepresented to prove
      that the shape of nuclear erythrocytes, as a mathematical expectation, is really
      the ellipse. Inaddition, allowable limits of deviation of the erythrocytes shape
      from the ellipse were shown. On the basis ofthe presented data we have introduced
      a new parameter (named "ellipsoid coefficient") to evaluate how the realcell
      shape fits to the correct ellipse. The coefficient is the ratio of the real
      erythrocyte area (A) to the calculatedarea (S) obtained by a direct measurement
      of the erythrocyte major (M) and minor (m) axes. We assume thatthis parameter can
      be used in taxonomy of the vertebrate animals having nuclear erythrocytes.

PMID- 30198670
TI  - Medicare, Medicaid, and Children's Health Insurance Programs: Announcement of
      Revisions to the Provider Enrollment Moratoria Access Waiver  Demonstration for
      Part B Non-Emergency Ground Ambulance Suppliers and Home Health Agencies in
      Moratoria-Designated Geographic Locations. Revisions of the waiver demonstration.
AB  - This document announces revisions to the Provider Enrollment Moratoria Access
      Waiver Demonstration (PEWD) for Part B Non-Emergency Ground Ambulance Suppliers
      and Home Health Agencies. The demonstration was implemented in accordance with
      section 402(a)(1)(J) of the Social Security Amendments of 1967 and, as revised,
      gives CMS the authority to grant waivers to the statewide enrollment moratoria on
      a case-by-case basis in response to access to care issues and previously denied
      enrollment applications because of statewide moratoria implementation, and to
      subject providers and suppliers enrolling via such waivers to heightened
      screening, oversight, and investigations.

PMID- 30198671
TI  - [Recognition of Three Types of Plantation Wood Species with Near Infrared Spectra
      Coupled with Back-Propagation Network].
AB  - In this study, the near infrared spectroscopy coupled with Back-Propagation (BP)
      network was used for the recognition of three kinds of plantation wood
      (Eucalyptus urophylla, Pinus massoniana, Populus X euramericana (Dode) Guineir
      cv. "San Martino" (1-72/58)). The study considered the effects of hidden layer
      neurons number, spectral pretreatment method and spectral regions on BP model,
      which are compared with SIMCA model simultaneously. The results showed that, (1)
      the recognition rate was 97.78% achieved by BP network model with hidden layer
      neurons number 13 and the spectral region of 780~2 500 nm. (2) BP model with
      spectral region of 780~2 500 nm was more robust than the other two BP models with
      spectral regions of 780~1 100 and 1 100~2 500 nm, of which recognition rates were
      97.78%, 95.56% and 96.67%, respectively. After the full spectra was pretreated
      with the first derivative and the second derivative methods, the recognition
      rates of BP models fell down to 93.33% and 71.11%. However, the recognition rate
      of BP model rose to 98.89% with the full spectra being pretreated by the
      multiplicative scatter correction (MSC). (3) Compared with SIMCA models that
      recognition rates of three spectral regions (780~2 500, 780~1 100 nm, and 1 100~2
      500 nm) were 76.67%, 81.11% and 82.22% respectively, BP network work models had
      higher recognition rates.

PMID- 30198673
TI  - CONTENT OF 70 kDa STRESS PROTEIN DURING ACCLIMATION OF MUSSEL MYTILUS EDULIS L.
      TO LOW SALINITY.
AB  - The paper deals with the dynamics of stress-proteins content in gill epithelium
      of bivalved mollusks Mytilusedulis in the course of their phenotypic adaptation
      to the changes of environmental salinity. It has beenshown that in low salinity
      (10 0/00) causing the work of "isolating reflex", the induction of stress
      proteins fromHSP70 family comes on the 5th day of the acclimation. Parallel
      measurements of the mussels extravisceral liquidosmolarity have shown that the
      signal for stress-protein induction in these mollusks is the osmolarity of
      theirinner medium, but not the salinity of marine water outside.

PMID- 30198672
TI  - HORMONAL STATUS AND ACTIVITY OF THE ANTIOXIDANT SYSTEM OF SOLANUM TUBEROSUM UNDER
      THE ACTION OF COLCHICINESAS THE INHIBITOR OF MICROTUBULE.
AB  - The content and the ratio of phytohormones, the activity of enzymes-antioxidants
      and lipid peroxidation,contents of proline and carotenoids in potato plants under
      the action of colchicines have been investigated.We have identified specific
      changes in hormonal balance of the plant initiated by the destructor of
      microtubules,colchicines (1 mM). We have found significant decreased in the
      amount of indoleacetic acid and zeatin, increasein the content of abscisic acid,
      no changes in the level of gibberellic acid, a decreased in the ratio
      betweenhormones-stimulants and abscisic acid. At this hormonal background, we
      observed activation of low molecularweight antioxidant system (increased levels
      of proline and carotenoids), while the peroxidase activitydecreased slightly, and
      catalase activity did not change. Monitoring of reactions of lipid peroxidation
      showedthe activation of its initial stages (accumulation of hydroperoxides), and
      then the process stabilized (the level ofmalondialdehyde did not change). We have
      concluded that the formation of hormonal status Solanum tuberosum,as well as the
      work of the antioxidant system, depend on the structural condition of the tubulin
      cytoskeleton.

PMID- 30198674
TI  - [The Chemical Composition of Bamboo after Heat Pretreatment with Fourier Infrared
      Spectrum Analysis].
AB  - Thermochemical pretreatment of lignocellulosic biomass is a critical step in
      obtaining high yields of cellulose and hemicellulose-derived sugars to realize
      effective utilization of cellulose in renewable biofuels. The pretreatment
      process can quickly remove hard dissolving lignin and the physical separation of
      hemicelluloses in the cell wall while changing the chemical composition in plant
      cell wall, so as to increase the production of lignocellulose. Research with
      medium of sulfuric acid (H(2)SO(4)), dilute alkali (NaOH) and glycerin, and at
      different pretreatment temperature (117 and 135 C in sulfuric acid (H(2)SO(4))and
      dilute alkali (NaOH) , 117 C in glycerin) analyzed and compared the main changes
      of chemical composition before and after the bamboo processing, and further
      confirmed that the mechanism of the chemical conversion after chemical
      pretreatment of bamboo through the Fourier infrared spectrum. The results showed
      that the output cellulose increased significantly after the thermochemical
      pretreatment. The change rules for yield of cellulose and the removal rate of
      lignin under the different pretreatment condition had been indicated dilute
      alkali (NaOH) treatment effect is better than that of dilute acid (H(2)SO(4)) and
      glycerin. In addition, the effect is more remarkable under the condition of 135 C
      than 117 C in the same medium. The changes of degradation degree of hemicellulose
      with different processing conditions were the same. The infrared spectrum
      analysis provided that C-O-C asymmetric stretching vibration peak appeared in
      cellulose decomposition after heat treatment, and it is the obvious steep fall in
      hemicelluloses infrared absorption characteristic peaks, benzene ring
      characteristic absorption peak of lignin has been abated. It is prove that yield
      of cellulose increased significantly, degradation trend of hemicelluloses is
      obviously, removal effect of lignin has also been better. The analysis results of
      Fourier infrared spectrum are consistent with the standard measurement.

PMID- 30198675
TI  - FEATURES ULTRASTRUCTURAL ORGANIZAITION OF SENSORY NEURONS IN THE ABDOMINAL
      MUSCLES RECEPTOR ORGANS CRAYFISH ASTACUS LEPTODACTYLUS.
AB  - Despite the fact that abdominal muscle receptor organ crayfish is one of the most
      thoroughly studied objectsin neurobiology, the ultrastructural mechanisms that
      make up its two different operating systems are disclosedinsufficiently as the
      focus of these papers was paid to the area of representation of dendrites of
      sensoryneurons in the receptor muscles. Detailed comparative analysis of the fine
      structure of the soma sensory cellswas not conducted. In the present study, we
      have investigated the ultrastructure of soma of slow- and fast-adaptingsensory
      neurons of abdominal muscle receptor organ Astacus leptodactylus with special
      attention to thedifferences between the two systems. Differences in the fine
      structure of the main cell organelles have beenidentified and quantified. We have
      discovered a relatively high concentration of mitochondria in sensitive cellsof
      slow type receptor as well as a large total area of tanks of the endoplasmic
      reticulum cells in neurons of fastersystem. We have assumed that the differences
      revealed in the fine structure of organelles in soma of sensory neuronsbetween
      the two types of receptors might be partially responsible for the speed of
      adaptation and for sensitivitythresholds observed in the physiological
      experiments.

PMID- 30198676
TI  - STRUCTURAL CHARACTERISTICS OF HUMAN AND OTHER MAMMALIAN ENDOTHELIAL CELLS.
AB  - Endothelial cells perform a number of important functions in the organism, and
      their dysfunction plays animportant role in pathogenesis of a wide range of
      diseases. This review deals with the current literature data onstructural
      characteristics of endothelial cells. A special section is devoted to endothelial
      cells development anddifferentiation. Structural aspects of endothelial cells
      cytoplasm and transport structures organization are discussed.Particular
      attention is paid to the structural heterogeneity of endothelial cells. Data on
      planar and apical-basal polarity of endothelial cells are reviewed separately.

PMID- 30198677
TI  - THE MOLECULAR MECHANISMS OF STEROIDOGENESIS REGULATION IN LEYDIG CELLS.
AB  - The synthesis of testosterone (T) in the male organism is carried out by Leydig
      cells located in the testesand controlled by luteinizing hormone (LH) produced by
      the anterior pituitary. The LH specifically binds to LHreceptors located in the
      plasma membrane of Leydig cells and stimulates the activity of intracellular
      signalingpathways coupled with the receptor, which regulate the steroidogenesis.
      The main role in this regulation belongsto the adenylyl cyclase signaling system
      which, along with LH receptor, includes Gs-protein, the enzymeadenylyl cyclase
      catalyzing the cAMP synthesis, and cAMP-dependent effector proteins. In mammals,
      the processof steroidogenesis is carried out with the participation of StAR
      protein which transports cholesterol intothe mitochondria, where the initial
      steps of T synthesis occur. The process also involves four steroidogenic
      enzymes,such as cytochrome P450scc, 3b-hydroxysteroid dehydrogenase (3b-HSD),
      cytochrome P450-17a possessing17a-hydroxylase and C17,20-lyase activities, and
      17b-hydroxysteroid dehydrogenase (17b-HSD). In different species of mammals and
      at the different stages of ontogenesis, the order of the reactions of T synthesis
      and their regulation are characterized by a number of differences. There are D4
      and D5 ways of T synthesis, which differ in the stage of isomerization including
      the displacement of the double bond from the C5-C6 positionto the C4-C5. The
      regulation of T synthesis can take place both by direct interaction of LH
      dependent signalingpathways with StAR protein, and indirectly, through the
      regulation of transcription factors controllingthe expression of genes encoding
      the steroidogenesis enzymes. In the present review the data on the
      molecularmechanisms of regulation and the ways of T synthesis in mammalian Leydig
      cells, the species specificity ofthese ways, as well as on the factors
      influencing the steroidogenesis are summarized and analyzed.

PMID- 30198678
TI  - Final Requirement--State Technical Assistance Projects To Improve Services and
      Results for Children Who Are Deaf-Blind and National Technical Assistance and
      Dissemination Center for Children Who Are Deaf-Blind (TA&D-DB). Final
      requirement.
AB  - The Assistant Secretary for Special Education and Rehabilitative Services
      announces a requirement under the Technical Assistance and Dissemination to
      Improve Services and Results for Children with Disabilities (TA&D) program. The
      Assistant Secretary may use this requirement forcompetitions in fiscal year (FY)
      2018 and later years.

PMID- 30198679
TI  - PROONCOGENIC EFFECTS OF INHIBITING THE microRNA miR-106A IN SKIN MELANOMA CELLS
      IN VITRO.
AB  - One of the regulators of gene expression at the post-transcriptional level are
      miRNAs. Due to its multifunctionality,these molecules are considered as potential
      targets for controlling the biological behavior of tumorcells. To date, several
      thousand types of microRNAs have been identified and their expression profiles
      haveshown significant during malignant transformation of cells. In this study, we
      have investigated the effect ofmiR-106a functional inhibition on the growth,
      viability and apoptosis of melanoma cells. Comparative analysisof expression
      profiles in melanona cells and in cells of melanocytic nevi identified by the use
      of microarray hasrevealed a significant increase in the miRNA expression level in
      melanoma cells. Despite this, inhibition of thismolecule in melanoma cells has no
      antitumor effect on cell proliferation, viability, migration activity and
      apoptosisof melanoma cells, but increases invasive activity and the ability to
      form colonies. The paper discusses theimportance of evaluating changes in miRNA
      levels in melanoma and other malignancies, relationship ifmiR-106a with the
      pathogenesis of melanoma, as well as the possible role of miR-106a in other
      pathologies.

PMID- 30198680
TI  - [Design and Fabrication of Silver Nanoparticles/Graphen Complex Substrate and Its
      Application for Detecting Uranium (VI)].
AB  - Uranium is one of the important nuclear materials to nuclear industry. Because of
      the direct disposal of spent fuel, there is still a huge possibility that uranium
      migrates into the groundwater, causing water contamination. It is of great
      importance to understand the concentration and their species distribution in
      aqueous solutions. Surface-Enhanced Raman Scattering (SERS) technique has been
      widely used for the detection of uranium (VI). However, the interactions between
      uranium (VI) and SERS substrate cause the symmetric stretching vibration peak of
      uranium (VI) shift to low wave number direction, which is unfavorable for
      confirming the species of uranium (VI) in aqueous solution. For instance, the
      normal Raman bands of uranyl in nitric acid solution are 871 cm-1, which belongs
      to the symmetric stretching mode of UO2+2. However, it moves to 710 cm-1 on the
      surface of silver nanorods SERS substrtate. What's more, different SERS substrate
      causes different number of shift. Graphene has advantages of inertness and
      integrity as well as 2-dimensional thickness. In this paper, graphene-isolated
      SERS substrate which is silver nanoparticles (AgNPs)/graphene complex substrate,
      was designed to prevent the interaction between SERS substrate and it was
      analyzed by using the inert graphene layer. First of all, according to our
      previous work, AgNPs SERS substrate was fabricated on silicon wafer by using an
      ascorbic acid-actived self-assembly method. Then, AgNPs/graphene complex
      substrate was prepared by transfering monolayer graphene onto the self-assembly
      AgNPs substrate. The morphology of complex substrate was obtained by SEM. Some
      AgNPs link together closely to form nanochain structures. Nanochain structures
      were distributed evenly on the surface of silicon wafer. The 2-dimensional
      thickness of graphene did not affect the morphology of AgNPs. When using the
      complex substrate to detect uranyl nitrate (5*10-4 mol.L-1),the Raman peak that
      appeared around 771 cm-1 is considered to be the symmetric stretching mode of
      UO2+2, shifting back about 52 cm-1 to high wave number direction when compared
      with AgNPs substrate, which was about ~719 cm-1. The result indicates that
      graphene layer isolates the interaction between AgNPs substrate and uranyl in
      some degree.

PMID- 30198681
TI  - MAST CELLS IN DAMAGED LYMPH-HEART STRIATED MUSCLE OF ADULT FROG: AN
      ULTRASTRUCTURAL, IMMUNOCYTOCHEMICAL AND AUTORADIOGRAPHIC STUDY.
AB  - Ultrastructural features of mast cell activation were studied in
      degenerative/reparative experimental modelof mechanically damaged lymph-heart
      striated muscle during the first postoperative week. 24 h after damage,the
      intracytoplasmic empty degranulation channels were revealed in a certain part of
      resident and circulatingmast cells (MCs) located near the site of injury. These
      findings are evidence that previously ther was activationand secretory response
      of MCs by a process known as compound exocytosis which involves not only granule
      to-plasma membrane fusions and formation of degranulation channels. We have found
      rare MCs showing release of single. altered, membrane-free granules into the
      space restricted by the plasma membrane of mature residentMCs and the basal
      lamina surrounding them. During the fist postoperative week we have more
      commonlyobserved activated lymph-heart MCs with prominent intragranular changes
      characterized by diminishing ofelectron-dense component of granules and loss of
      granule matrix. We have also revealed close association ofsome unaltered and
      altered secretory granules with completely or partially empty degranulation
      channels thatpermeate the mast cell cytoplasm. Some of these channels remained
      open directly to the exterior of the cells. Itis not improbable that these
      findings provide the ultrastructural basis for potential discharge of small
      amountsof granule mediators into the open channels (incomplete exocytosis) duding
      partial degranulation of activatedin vivo frog MCs. Immunocytochemical staining
      for histamine of activated frog MCs showed the presence ofthe immunoreactive
      material both in unaltered and altered cytoplasmic granules. As a rule, gold
      particles werelocated over residual electron-dense component of altered granule,
      whereas little or no gold particles were revealedover the swollen matrix.
      Ultrastructural features of secretory granule formation in the cytoplasm of
      someMCs were observed toward the end of the first postoperative week. Electron
      microscopic autoradiography hasshown that replicative and transcriptional
      activity of MCs is not observed in the studied postoperative period.No mitoses in
      MCs have been revealed in this period. A few mast cells were found in necrosis.
      Taken together,our results indicate that MCs are one the first cell types that
      respond to injury of lymph-heart striated muscleand release a variety of
      preformed mediators, including histamine. These findings suggest that activated
      MCsplay an important role in the initiation of an inflammatory process during
      repair of damaged lymph-heart striatedmuscle.

PMID- 30198682
TI  - [Raman Spectra Study on the Structure and Thermal Stability of Vacuum Annealed Cr
      DLC Films Prepared with UBMS].
AB  - Chromium doped amorphous hydrogenated carbon a-C?H(Cr) films (2.23 MUm in
      thickness)have been successfully prepared with unbalanced magnetron sputtering
      technology(UBMS) in this paper. Raman spectrum and X-ray photoelectron
      spectroscopy (XPS) have been used to study the structure and thermal stability of
      the Chromium doped diamond-like carbon films (Cr-DLC). The results indicate that,
      at the room temperature, the Raman absorption peak "G" near 1 580 cm-1was
      assigned to C-C stretching vibration mode (E2g) in the Cr-DLC films, while the
      peak "D" near 1 350 cm-1was assigned to sp2 breathing vibration mode (A1g). The
      relative concentration of sp3 bond in the film is at 48%. When heated till 300 C,
      the Raman pattern of sample is similar to that of the sample at room temperature,
      indicating the structure of Cr-DLC film is stable. At 400 C, the ratio of ID/IG
      and the concentration of sp2 bond clearly increase, indicating the change of the
      structure in the Cr-DLC and the appearance of graphitization. With temperature
      going up, the rise of ID/IG ratio and the shift of the peak "G" to high
      wavenumber show that the rise of sp2/sp3 ratio, the intensity of graphitization,
      and the decline of the disorder of sp2 in the Cr-DLC films lead to the increase
      of the friction coefficient and wearing rate and the decline of the Cr-DLC
      thermal stability. When the it is up to 600 C, the ratio of ID/IG and the
      concentration of sp2 bond reach the max value while the Cr-DLC film loses its
      efficacy.

PMID- 30198683
TI  - Medicare Program; Certain Changes to the Low-Volume Hospital Payment Adjustment
      Under the Hospital Inpatient Prospective Payment Systems (IPPS) for Acute Care
      Hospitals for Fiscal Years 2011 Through 2017. Application of a payment
      adjustment.
AB  - This document announces changes to the payment adjustment for low-volume
      hospitals under the hospital inpatient prospective payment systems(IPPS) for
      acute care hospitals for fiscal years (FYs) 2011 through 2017 in accordance with
      section 429 of the Consolidated Appropriations Act, 2018.

PMID- 30198684
TI  - QUANTIFICATION OF MITOCHONDRIAL MORPHOLOGY IN SITU.
AB  - Structural organization of mitochondria reflects their functional status and
      largely is an index of the cell viability.The indirect parameter to assess the
      functional state of mitochondria and cells is the degree of fragmentation,i. e. a
      ratio of long or branched mitochondrial structures to rounded mitochondria. The
      critical need forsuch evaluations requires the creation of an approach, that
      allows on the basis of confocal images of mitochondriastained with a fluorescent
      probe, to create an integral picture of the three-dimensional organization of
      mitochondria.In the present study, we tested three approaches to analyze the
      structural architecture of mitochondriaunder norm and fission induced by
      oxidative stress. We have revealed that while the most informative way ofanalysis
      is a three-dimensional reconstruction based on series of confocal images taken in
      Z-dimension, however,with some limitations it is plausible to use more simple
      algorithms of analysis, including that one that usesunitary two-dimensional
      images. Further improvement of these methods of image analysis will allow
      morecomprehensive analysis of mitochondrial architecture under norm and different
      pathological states. It may alsoprovide quantification of a number of
      mitochondrial parameters determining morpho-functional state of
      mitochondriaprimarily their absolute and relative volumes and give additional
      information on three-dimensional organizationof mitochondriome.

PMID- 30198685
TI  - [Study on Non-Detective Determination of beta-Carotene Content in Loquats with
      Raman Spectroscopy].
AB  - In china, researches on Raman spectroscopy in terms of foodstuff mainly focus on
      carbohydrates, fatty acids, proteins and vitamins. Conventional methods for
      determining the carotenoids content require the extraction of the samples as well
      as other cleanup steps. In this work, Raman spectroscopy is applied to get the
      measured value form loquats with different mature stage which are compared with
      the reference value get from High Performance Liquid Chromatography (HPLC),in
      order to find new, fast, and nondestructive calibration methods for
      quantification of beta-carotene content in loquat fruits. Least Squares Support
      Vector Machine and Partial least squares data processing methods are used to
      analyze the Raman spectra while PLS model has a prediction quality with the
      correlation coefficient of 0.845; the root-mean-square error of 0.022 MUg.g(-1)
      and LS-SVM model has a better prediction quality with the correlation coefficient
      of 0.910 with the root-mean-square error of 0.058 MUg.g(-1).

PMID- 30198686
TI  - INTERMOLECULAR INTERACTIONS IN THE SOLUTIONS OF SERUM ALBUMIN.
AB  - The mechanisms of intermolecular protein complex formation were studied by the
      example of monomers,oligomers and aggregates of bovine serum albumin (BSA)
      depending on the protein concentration, pH and ureaconcentration. Using dynamic
      light scattering (DLS), analytical ultracentrifugation (AUC) and PAG
      electrophoresis,we have shown that there is dynamic equilibrium between monomers
      and aggregates in BSA solution.Decreasing pH of the solution (4.0-1.0) resulted
      in increasing sizes of the aggregates. In the solutions withlow urea
      concentrations (below 2 M), the sizes of aggregates decreased, while higher urea
      concentrations inducedformation of larger aggregates due to the unfolding of the
      protein.

PMID- 30198687
TI  - Schedules of Controlled Substances: Temporary Placement of N-Ethylpentylone in
      Schedule I. Temporary amendment; temporary scheduling order.
AB  - The Acting Administrator of the Drug Enforcement Administration is issuing this
      temporary scheduling order to schedule the synthetic cathinone, 1- (1,3
      benzodioxol-5-yl)-2-(ethylamino)- pentan-1-one (N-ethylpentylone, ephylone) and
      its optical, positional, and geometric isomers, salts, and salts of isomers in
      schedule I. This action is based on a finding by the Acting Administrator that
      the placement of Nethylpentylone in schedule I of the Controlled Substances Act
      (CSA) is necessary to avoid an imminent hazard to the public safety. As a result
      of this order, the regulatory controls and administrative, civil, and criminal
      sanctions applicable to schedule I controlled substances will be imposed on
      persons who handle (manufacture, distribute, reverse distribute, import, export,
      engage in research, conduct instructional activities or chemical analysis, or
      possess), or propose to handle N-ethylpentylone.

PMID- 30198688
TI  - THE INFLUENCE OF VITAMIN C ON THE DYNAMIC OF RELATION OF COLLAGEN I AND III TYPES
      IN THE PERIPROSTHESIS AREA.
AB  - The aim of the study was to learn the degree of biocompatibility of synthetic
      herniological prostheses"Progrip", with collagen-stimulating effect of ascorbic
      acid on the growth of connective tissue in the experiment.We examined
      characteristics of collagenogenesis in the anterior abdominal wall depending on
      the effectof vitamin C using the method of polarization microscopy. We suggest a
      new way to stimulate reparation processby ascorbic acid which would help to
      optimize forming functionally matured structures of connective tissueof the
      anterior abdominal wall surrounding endoprosthesis. Due to the results of our
      investigation it has beenclear that modification effect of vitamin C is positive
      for synthesis of collagen in the periprosthetic capsulefor any type of
      endoprosthesis. It has been proves by statistically reliable increase in ratio of
      collagen types Iand III when vitamin C is used in the diet of experimental
      animals.

PMID- 30198689
TI  - [In Situ Research on Ginger Oil Cell with Raman].
AB  - This article presents a novel and original approach to analyze the main
      components of the essential oils in ginger oil cell by means of Raman
      spectroscopy. Fresh ginger sample was prepareed with free-hand section. Under the
      DXR Laser confocal micro Raman spectrometer, the oil cell has 20 objective lens.
      As to the ginger oil cell, the Raman spectrum, all together 21 spectroscopic
      bands, was obtained. It has been found that the obtained Raman spectrums at
      different oil cells are very similar. The Raman spectrum of the commercial
      essential oils of ginger, together 37 spectroscopic bands, was obtained. It has
      been found that the 19 presented spectroscopic bands of ginger oil cell correlate
      very well with those obtained by the commercial essential oils. Density
      Functional Theory (DFT) of zingiberene calculations were performed in order to
      interpret the spectra of the essential oils of the ginger oil cell and essential
      oils of ginger. There are 31 spectroscopic bands of the essential oils of ginger,
      and 19 spectroscopic bands of ginger oil cell correlate very well with
      calculations. All these investigations are helpful tools to generate a fast and
      easy method to control the quality of the essential oils with Raman spectroscopic
      techniques in combination with DFT calculations.

PMID- 30198690
TI  - THE COMPARATIVE CHARACTERISTIC OF MORPHOLOGY AND PROLIFERATIVE ACTIVITYOF
      COELOMIC FLUID AND COELOMIC EPITHELIUM CELLS IN STARFISH ASTERIAS AMURENSISAND
      STARFISH A. RUBENS.
AB  - Identification and characterization of cells responsible for the restoration of
      tissues in adult organisms isone of the main problems in regenerative biology. In
      this study, the comparative histological analysis of cellularsuspensions in
      coelomic fluid (CF) and coelomic epithelium (CE) of two close species of
      Asteroidea has beendone. Particular attention was paid to characteristics of
      small epithelial cells (SECs, diameter 4 mm) with highnuclear-cytoplasmic ratio
      more 0.9 and without visible signs of differentiation. Cells of this type
      constitute asignificant proportion in CE in Asterias rubens, show proliferative
      activity and are probably the progenitor cellsfor the coelomocytes. Small cells
      with parameters identical to those of A. rubens SECs have been found both inCF
      and CE of A. amurensis. We have found subpopulation of weakly attached CE cells
      highly enriched withSECs-1. These cells were able to migrate from CE. Analysis of
      adhesion ability of CF and CE cells has revelaledthe same patterns for these two
      closely releated starfish. Two-week primary cultures have demonstrated
      thespeciality of A. amurensis CE cells consisting in the formation of "crystals",
      the potential centers of spiculogenesis that have not been revealed in A. rubens.
      Both small cells and larger cells with nuclear-cytoplasmic ration lower than 0.7
      demonstrated proliferative activity in vivo and in vitro. Moreover, more high
      mitotic activity of coelomocytes has been found in A. amurensis. The hypotheses
      of coelomocytes origin are discussed.

PMID- 30198691
TI  - [A Quercetin-Based Fluorescent Probe for the Recognition of Fluorid Ions].
AB  - Quercetin (Q) is one of the most common flavonoids present in roots, stems,
      leaves, flowers and fruits of most plants. In this study, a quercetin-based
      fluorescent probe for detecting fluorid ions had been proposed. With good
      selectivity and sensitivity for fluorid ions, Q-based fluorescent probe was
      easier to prepare, more eco-friendly and more innoxious compared with traditional
      fluorescent probe obtained by organic chemistry synthesis operation. There was a
      major fluorescence emission peak at 500 nm for Q in dimethyl sulfoxide (DMSO)
      when the excitation wavelength was 390 nm. The changes of fluorescence spectra
      were investigated before and after adding different anions into Q solution. The
      fluorescence emission intensity of Q even had no change when adding Cl-,Br-,I
      ,ClO-4,H2PO-4, respectively. While adding fluorid ions, the fluorescence emission
      intensity of Q was decreased obviously, which suggested fluorid ions could induce
      fluorescence quenching of Q in DMSO. And the fluorescence emission intensity of Q
      F- system had almost no significant change when adding other anions (Cl-,Br-,I
      ,ClO-4,H2PO-4), which meant the progress for detecting fluorid ions didn't be
      affected by other anions, and Q showed a good selectivity for fluorid ions. The
      fluorescence titration spectra showed that the fluorescence emission intensity of
      Q was decreased with the increase of concentration of fluorid ions, and they were
      in concentration-dependent manner. The fluorescence titration curve exhibited
      that the Q as fluorescent probe can be applied to the quantification of fluorid
      ions with a good linearity (R2=0.991), linear range of 1.0~8.0*10-6 mol.L-1 and
      the detection limit of 1.0*10-7 mol.L-1. Not only the changes appeared in
      fluorescence spectra, but also the changes appeared in UV-visible spectra,
      compared with Q absorption spectrum, the location of band at 375 nm had no change
      after adding Cl-,Br-,I-,ClO-4,H2PO-4, respectively. However, when adding fluorid
      ions, the band at 375 nm was shifted to 394 nm, and the color of the solution was
      changed into dark yellow, which revealed the interactions between Q and fluorid
      ions. The probable mechanism of fluorid ions inducing fluorescence quenching of Q
      was obtained with 1H NMR spectrum and the changes of fluorescence emission
      intensity of Q-F- system in different polar solvents (DMSO containing different
      concentration of water). The interaction mode about Q and fluorid ions in DMSO
      was related with hydrogen bond. Both experiments suggested that the possible
      recognition mechanism on fluorid ions was: fluorid ions were destroyed or
      weakened by original hydrogen bonds, and were promoted charge transfer within
      quercetin molecule, which resulted in fluorescence intensity decreasing of
      quercetin. This method was successfully applied in detecting fluorid ions of
      samples in DMSO with good recovery.

PMID- 30198692
TI  - The Protective Effect of Sunlight against Influenza.

PMID- 30198693
TI  - MICRORNAS AS ULTRAVIOLET IRRADIATION EFFECTS REGULATORS IN SKIN CELLS.
AB  - MicroRNAs belong to small non-coding RNA which regulate gene expression via mRNA
      degradation ortranslation inhibition. MicroRNAs are active modulators of gene
      expression in the skin caused by exogenousfactors including ultraviolet
      irradiation. These effects are realized by targeting transcription factors and
      signalingsystems components. Changes in microRNAs levels started to register in a
      few hours after exposure toultraviolet irradiation, wich confirms the presence of
      an effective fast processes in the scin cells that modulatethe functional status
      of microRNAs. The reported recently ability of microRNAs to be transported by
      exosomesmay be related to systemic effects of ultraviolet irradiation that
      include the altered immune response and systemicinflammatory reaction.
      Understanding these processes is important because of the possibility of
      purposefulinfluence on the expression and activity of a microRNA that may have
      implications for diagnosis and therapy ofphotodermatosis and malignant skin
      tumors.

PMID- 30198694
TI  - [Research on Spectrum Matching Method for PbSe Quantum Dots Luminescence Spectrum
      and Gas Absorption Spectrum].
AB  - As typical nano metarials in near infrared waveband, PbSe Quantum Dots have a
      very large exciton Bohr radius of 46 nm and a small band gap of 0.28 eV at room
      temperature. PbSe QDs have very unique properties, such as the quantum confined
      optical property, and which possess high photoluminescence (PL) quantum yield
      (QY) with size dependent tunable wavelength emissions. By analyzing the
      luminescence spectrum of PbSe Quantum Dots, a method through adjusting the
      particle size of PbSe Quantum Dots (QDs) to match gas absorption spectrum was
      presented in this paper. 4.6 and 6.1 nm PbSe QDs were synthesized and deposited
      on the GaN chip to fabricate the NIR QDs light sources. The PbSe QDs-UV glue
      composites thickness was determined to be 48.0 and 671.5 MUm for 6.1 and 4.6 nm
      PbSe QDs. The NIR QDs were used to detect the C2H2 and NH3 gas. The experiments
      show that the PL spectrum of 4.6 nm NIR QDs can cover the entire absorption
      spectrum of C2H2 gas (from 1 500 to 1 550 nm) and the PL spectrum of 6.1 nm NIR
      QDs can cover the entire absorption spectrum of NH3 gas (from 1 900 to 2 060 nm).
      By changing the quantum size of QDs, the PL peak of the NIR QDS light source can
      be adjusted to cover the absorption peak of different gases. The matching method
      presented in this paper is efficient and feasible, which has great application
      potential in gas detection.

PMID- 30198695
TI  - DEVELOPMENT OF SINGLE-DOMAIN NEAR-INFRARED FLUORESCENT PROTEIN GAF-FP BASED ON
      BACTERIAL PHYTOCHROME.
AB  - Fluorescent proteins (FPs) are widely used as genetically encoded markers for
      noninvasive and quantitativestudy of biological processes. Development of
      biomarkers that fluoresce in the near-infrared spectral rangeallows the study of
      animals at a deeper level due to high permeability of tissues to light in this
      wavelength range,compared to the visible light. For widespread use of FPs, such
      properties as low molecular weight and themonomer become important. In this
      paper, we developed a FP called the GAF-FP and based on the chromophore-binding
      domain of bacterial phytochrome from Rhodopseudomonas palustris (RpBphP1). GAF-FP
      has a molecularmass of ~ 19 kDa, 2 times lower than that of other FP based on
      BphPs and 1.4 times less than the commonlyused GFP-like proteins. Unlike most
      other near-infrared FP, GAF-FP is a monomer, has high photostabilityand its
      structure can withstand the introduction of small peptide inserts. Moreover, GAF
      FP can covalentlybind two different tetrapyrrole chromophores: phycocyanobilin
      (PCB) and biliverdin (BV), which is found inmammalian tissues. GAF-FP with BV as
      a chromophore (GAF-FP-BV) has a main absorption band with amaximum at 635 nm and
      fluorescence maximum at 670 nm, whereby GAF-FP has a high signal to
      backgroundratio even if localized at a depth of several mm below the tissue
      surface. Apart from the near-infrared absorptionband, GAF-FP-BV also has also an
      absorption band in the violet spectral range with a maximum at378 nm. This
      property has been used by us to create a chimeric protein consisting of a
      modified luciferase fromRenilla reniformis (RLuc8) and GAF-FP. We have shown that
      the chimeric protein is capable of resonanceenergy transfer from the substrate,
      which is oxidized by luciferase, to chromophore of GAF-FP-BV. In the absenceof
      energy acceptor, RLuc8 catalyzes the cleavage of the substrate with light
      radiation having a peak of400 nm. At the same time, as a part of GAF-FP-RLuc8
      chimeric protein, the energy from the substrate is transferredto the chromophore
      of FP and then emitted in the near-infrared spectral range corresponding to GAF
      FPfluorescence. These results open the way for the creation of new small near
      infrared FPs based on various naturalBphPs with a prospect of their wider use in
      cell and molecular biology.

PMID- 30198696
TI  - SODIUM BUTYRATE ENHANCES THE ANTIPROLIFERATIVE EFFECT OF HIGH CONCENTRATIONS OF
      ACTINOMYCIN D.
AB  - In the present article we have studied the combined effect of actinomycin D (AMD)
      with HDI sodium butyrate(NaBut) on proliferation of transformed cells. It has
      been shown that NaBut increased the cytotoxic effectof low concentrations of AMD
      (8 nM). However, the viability of the cells transformed with E1A + Raswas
      slightly increased under the joint action of high concentrations of AMD and
      NaBut. Simultaneous action ofNaBut and low concentration of AMD sharply reduced
      the clonogenic survival of transformed cells, in parallelwith increased apoptotic
      cell death.The study of the mechanisms of cell death induced by the combined
      actionof NaBut and low concentrations of AMD showed that the joint treatment
      resulted in activation of proapoptotictranscription factor p53 and the
      suppression of the activity of anti-apoptotic factor NF-kB. Thus, NaBut
      increasedcytotoxic effect of low concentrations of AMD in oncogene-transformed
      cells under the joint action, increasingtheir apoptotic death. These results can
      be used in the selection of the correct dosage of drugs for the effectivecombined
      anti-cancer therapy using HDIs and AMD.

PMID- 30198697
TI  - [Research on Water Quality Analysis Model with PCA Method and UV Absorption
      Spectra].
AB  - Using the UV absorption spectrum to detect Organic pollutants content in water
      has become one of the most important methods for real-time online monitoring in
      the field of water quality inspection, however, the water complex and unstable
      components often bring much uncertain offset to the standard test. In this paper,
      water samples were classified firstly by analyzing UV absorption spectrum ranging
      from 200 nm to 400 MUm including the organic substances, through the way of
      combining principal component analysis (PCA) with Euclidean distance. In this
      paper, we compared the Principal component analysis combined with partial least
      squares regression (PCA-PLSR) and the direct multi-wavelength absorption models
      combined with partial least squares regression (MWA-PLSR), not only for the real
      water sample but also for the analysis of different concentrations of COD
      standard solution. The result indicates that the measurement errors of the PCA is
      less than 5%, it is the smallest by using the first and second principal
      components as regression parameters for PLSR. Using the methods above can
      simultaneously achieve to classify of water samples and to measure the
      concentration of water quality parameters more accurately.

PMID- 30198698
TI  - Health Benefits of Congestion Pricing.

PMID- 30198699
TI  - CHARACTERISTICS OF AMYLOID DEPOSITS DETECTED IN THE INTERNAL ORGANS OF mdx MICE.
AB  - The dystrophin-deficient mdx mouse is the most commonly used experimental model
      of Duchenne musculardystrophy (DMD). Although the amyloid has been shown in the
      muscle biopsies of patients with differenttypes of muscular dystrophies, there
      are no data on the amyloid accumulations in the biopsy of DMD patients ormdx
      mouse. Therefore, the aim of the present study was to testify the hypothesis of
      probable accumulationof amyloid in the visceral organs of mdx mouse. Specimens of
      myocardium, kidneys, and liver of male andfemale mdx mice aged from 2 months to
      1.5 years (n = 9) were used in the study. The histochemical stainingwith Congo
      red demonstrated amyloid accumulations in the studied organs of the mdx mice.
      Morphology andlocalization of the found accumulations were described in details
      and analyzed. The mass-spectrometric studydetermined the vitronectin and
      apolipoprotein A-II as the most probable components of the amyloid
      accumulationsin the mdx mouse.

PMID- 30198700
TI  - [Characterization of the Effect of Anion on the Complex of Oat beta-Glucan and
      Congo Red with UV-Vis Absorption Spectroscopy].
AB  - The effects of concentration and type of anions on aggregation of Congo red in
      solution were studied with UV-Visible spectroscopy. And the influence of anions
      on the complex of Congo red and oat beta-glucan was further studied. The results
      showed that the maximum absorption wavelength of Congo red in aqueous solution
      shifted toward the shorter wavelength, and the absorbency lowered considerably
      with increasing ionic concentration. There was a significant linear correlation
      between logarithm of anion concentration and the maximum absorption wavelength,
      with the peak absorbance, and the absorbance at 499 nm. The influence of anions
      on aggregation of Congo red was in accordance with Hofmeister series, indicating
      that hydrophobic interaction is an important driving force for Congo red
      molecules to assemble into micelles. As for the complexation of Congo red and oat
      beta-glucan, when the concentration of anions exceeded the first critical
      concentration, the micelle of Congo red began to form and then combined to beta
      glucan. The absorption peak of the complex presented at 556 nm. When the
      concentration of anions exceeded the second critical concentration, the complex
      was developed into supramolecular structure through aggregation of Congo red
      micelles on Congo red/beta-glucan complex, which resulted in the shift of
      absorption peak toward 583 nm. And the presence of Mie scattering effects at the
      longer wavelength indicated the formation of larger supramolecular structure. The
      effect of anions on the above supramolecular structures also followed the order
      of Hofmeister series, showing that the aggregation of Congo red/beta-glucan
      complex into supramolecular structure was mainly driven through hydrophobic
      interactions between Congo red micelles on the complex. The research indicated
      that ions had an important effect on the aggregation of Congo red and the
      interaction between biopolymers and Congo red.

PMID- 30198701
TI  - BIORESORPTION OF POROUS 3D-MATERIALS BASED ON CHITOSAN.
AB  - 3D-materials with high porosity were prepared by the method of lyophilization of
      chitosan solution. In vivoinvestigation of the mechanism and resorption rate of
      the resulting material in the muscle tissue showed completeresorption occuring in
      12 months after implantation in an animal. The formation of scar tissue was not
      observed;there was no change and damage of the surrounding tissue. Histological
      analysis showed that chitosanresorption occurred simultaneously with the
      formation of collagen fibers and blood vessels. This allows us torecommend such
      porous material based on chitosan as a matrix for tissue engineering.

PMID- 30198702
TI  - The Effect of Wait Time Targets in Emergency Departments.

PMID- 30198703
TI  - MORPHOFUNCTIONAL CHANGES OF JURKAT LINE T-LYMPHOBLASTS AT SHORT-TERM CONTACT WITH
      RELIEF CALCIUM PHOSPHATE SURFACE.
AB  - Human leukemic T-lymphoblastoid cells (hereinafter Jurkat T-cells) were used to
      model T-lymphocytesmorphofunctional reaction to 24-h in vitro contact with relief
      (roughness index Ra = 2.2--2.7 mm) pure titaniumsubstrates (12_12_1 mm3) covered
      by calcium phosphate (CP) bilateral coating that was preparedby micro-arc method.
      Jurkat T-cell culture on plastic surface of well plate (2D control of culture
      growth),as well as the cells that contacted for 24 h with oxide (TiO2) micro-arc
      coating on pure titanium substrate(3D control) served as comparison tests. 27--98
      % of immortalized cells in 2D control culture hadCD3+CD4+CD71+CD45RA+
      immunophenotype and secreted IL-2, IL-4, IL-8, IL-10 and TNFa, but not IL-1band
      IL-6. Other markers of cell activation, differentiation, maturation and death
      (CD8, CD16, CD56, CD25,CD95) were found at 0-2.5% of the cell population.
      Microtextured CP surface elevated statistically IL-8 outcometo 183 and 160 % of
      corresponding control values in 2D- and 3D-cultures of Jurkat T-cells. CD4/CD8
      ratiofell to 9 : 1 (at 13 : 1 and 82 : 1 in 2D- and 3D-controls, respectively)
      both by CD4+ depletion and by CD8+cell percent raise. Total amount of cells (TAC)
      in Jurkat T-cell culture after 24-h contact with CP coating wasdecreased to 88 %
      2D control level (P < 0.04) that could favor to a suppression of cell division.
      TAC reductionin Jurkat T-cell culture was accompanied by accelerated IL-8
      spontaneous secretion (r = -0.97, P < 0.00009).For all this, IL-8 induced
      apoptosis (r = 0.94, P < 0.0001) in low concentrations (pg/ml). The obtained
      result isthe feature of Jurkat T-cells reaction on CP but not TiO2 coatings, and
      it may be used in case of materials selectionfor endoprosthesis replacement and
      fracture osteosynthesis in patients suffering by hematological and
      bonemalignancies.

PMID- 30198705
TI  - Sulfonated Nanobamboo Fiber-Reinforced Quaternary Ammonia Poly(ether ether
      ketone) Membranes for Alkaline Polymer Electrolyte Fuel Cells.
AB  - Alkaline polymer electrolyte fuel cells (APEFCs) are a new class of
      electrochemical devices that intrinsically enable the use of nonprecious metal
      catalysts. As an important component of APEFCs, alkaline polymer electrolytes
      (APEs) have been a research focus in recent decades. To minimize the ohmic loss
      and to facilitate the water transport, the APE membrane should be as thin as
      possible, which generally requires a trade-off between the ionic conductivity and
      the mechanical robustness/dimensional stability of the membrane. Here, we report
      a new reinforced APE membrane that can effectively disentangle such a trade-off.
      The quaternary ammonia poly(ether ether ketone) (QAPEEK) membrane is highly
      conductive but suffers from the overuptake of water, which leads to significant
      membrane swelling and weak mechanical strength. Upon reinforcing with sulfonated
      nanobamboo fiber (s-NBF), the swelling degree decreases from 27.5 to 7.5% in 80 
      degrees C water. The thickness of such an s-NBF/QAPEEK membrane can then be
      reduced to 15 MUm, which diminishes the electrical resistance, very suitable for
      APEFC applications.

PMID- 30198704
TI  - EVALUATION OF VASCULOGENIC POTENTIAL OF MODIFIED FIBRIN HYDROGEL.
AB  - In recent years, engineering of blood vessels, which can provide the effective
      transport of nutrients and variousmetabolites, is one of the major challenges in
      tissue reconstruction. Many researches are carried out to developcell-seeded
      bioconstructs based on natural polymers, particularly on PEGylated fibrin.
      Therefore, the aimof this study was to reveal the optimal component ratio for
      modified fibrin hydrogels in order to provide favorableconditions for vascular
      development of endothelial and mesenchymal stem cell co-culture. It has beenfound
      out that the PEGylated fibrin hydrogels can support 3D cell growth in HUVECs and
      hASCs co-culture.The microporous filamentous hydrogel prepared from PEGylated 5 :
      1 fibrinogen and using the 1 : 0.2 proteinto thrombin ratio had the most
      favorable microenvironment for cell distribution, growth and development in
      thestudied co-culture that resulted in high levels of expression of proteins
      required for angiogenesis.

PMID- 30198706
TI  - Classics in Neuroimaging: Radioligands for the Vesicular Monoamine Transporter 2.
AB  - Positron emission tomography (PET) studies of the monoamine neurotransmitter
      systems in the human brain employ a variety of radiotracers targeting the many
      receptors, transporters, and enzymes present in monoaminergic neurons. One of
      these is the vesicular monoamine transporter 2 (VMAT2), the protein responsible
      for the energy-dependent accumulation of monoamines into synaptic vesicles. The
      development of in vivo imaging radiotracers for VMAT2 is a story of starting with
      a well-characterized clinically used drug (tetrabenazine) which had a
      pharmacologically active metabolite: that metabolite that was in stepwise fashion
      refined and modified to provide both carbon-11 and fluorine-18 labeled VMAT2
      radiotracers that are now used for human PET studies of neurodegenerative and
      psychiatric diseases. The design approach taken, which involved understanding the
      metabolism of the radiotracers and identification of the optimal ligand
      stereochemistry, are representative of important steps in the general concepts
      behind successful in vivo radiotracer design for brain imaging agents.

PMID- 30198707
TI  - Performance Improvement and Characterization of Spray-Coated Organic
      Photodetectors.
AB  - Low dark current organic photodetectors (OPDs) with a conventional structure
      consisting of poly(3-hexylthiophene) and [6,6]-phenyl-C61-butyric acid methyl
      ester (PCBM) as active layer have been fabricated by spray-coating. Tuning the
      thickness of active layer and thermal annealing process for the spray-coated OPDs
      results in a remarkable performance with a low dark current density ( Jd) of 2.90
      * 10-8 A/cm2 at reverse bias of 1 V. The impact of thermal annealing on the
      performance of sprayed OPDs is also investigated by the impedance analysis for
      mechanistic understanding. Our results demonstrate that the optimization of PCBM
      cluster and interfacial contact between the active layer and the metal electrode
      tailored by thermal annealing, respectively, could effectively reduce the Jd and
      increase the sensitivity of sprayed OPDs. The control of PCBM cluster is more
      important than the interfacial contact between the layers for improving Jd. In
      addition, structural characterization of the active layer studied by synchrotron
      small-angle X-ray scattering technique reveals why the spray-coated process can
      achieve the lowest dark current due to the favorable structure.

PMID- 30198708
TI  - Co-Transcriptional Molecular Assembly Results in a Kinetically Controlled
      Irreversible RNA Conformational Switch.
AB  - Co-transcriptional RNA folding results in dynamic behavior of RNA transcripts.
      Extra stimuli can perturb the stability of the nascent RNA and alter its
      conformation and function. Here, an artificial RNA conformational switch, which
      consists of a 5' aptamer unit for sensing thiamine pyrophosphate (TPP) and a 3'
      working unit (TAR RNA) that binds Tat peptide connected by a switching sequence,
      was designed and cotranscriptionally functionalized. Co-transcriptional binding
      of TPP induced an RNA conformational change that allowed interaction of Tat
      peptide and the TAR RNA unit. Two conformational states, which are mutually
      exclusive depending on the TPP binding, did not show post-transcriptional
      interconversion. The irreversible RNA conformational switch demonstrated here,
      which kinetically coupled co-transcriptional RNA folding and molecular assembly
      in nonequilibrium biological systems, will enable efficient switching of RNA
      functions applicable for constructing intracellular molecular sensors.

PMID- 30198709
TI  - A Strain-Deformation Nexus within Pincer Ligands: Application to the Spin States
      of Iron(II) Complexes.
AB  - The substitution of a pyrrolide ring for one (or more) pyridyl rings within the
      ubiquitous terpyridine (tpy, A) scaffold results in more open geometries of the
      pyridine-pyrrolide chelate ligands. DFT calculations (B3LYP-GD3BJ/6-31G**)
      demonstrate that the more open geometries of the unbound ligands are mismatched
      with the "pinched in" geometries required to chelate transition metal ions (e.g.,
      Zn2+). The strain which builds within these ligands (Delta EL(strain)) as they
      bind transition metal ions can be related to changes in a single geometric
      parameter: the separation between the two terminal N atoms (rho). This
      relationship applies more generally to other three-ringed tridentate pincer
      ligands, including those with different donor groups. The approach was applied to
      homoleptic iron(II) complexes to investigate the contribution of the steric
      effects operating within the ligands to the different magnetic properties,
      including spin crossover (SCO) activities, of these systems.

PMID- 30198710
TI  - A Critical Review of Existing Criteria for the Prediction of Pyrochlore Formation
      and Stability.
AB  - Depending on intrinsic (e.g., radius ratio rule rLn/ rZr) and extrinsic factors
      (e.g., processing conditions), pyrochlore-type Ln2Zr2O7 oxides achieve variable
      degrees of structural disorder. We report on a systematic study of the structural
      and microstructural characteristics of the Gd2- xLn xZr2O7 system, exploring the
      effect of replacing Gd with a wide range of homovalent lanthanide ions (Ln = Nd,
      Sm, Dy, Ho, Y, and Er; x = 0.20 and 0.80). All compositions were prepared via a
      mechanochemical reaction between the corresponding oxides and characterized by X
      ray diffraction (standard and synchrotron sources) using the Rietveld method, as
      well as by Raman spectroscopy. Irrespective of chemical composition, this study
      reveals that all compositions exhibit a fluorite-like structure. Furthermore, by
      firing each sample at 800 and 1400  degrees C, we are able to analyze the
      transition to pyrochlore-like structures, featuring different degrees of
      disorder, in all but Gd1.20Y0.80Zr2O7, which retains the fluorite structure even
      after heating. The structural data are used to assess the existing criteria for
      predicting the formation and stability of the pyrochlore structure; according to
      this analysis, the simple radius ratio rule ( rLn/ rZr), provides a useful and
      sufficiently robust criterion. Because the pyrochlore structure has a strong
      tendency to disorder, it is not possible to define an empirical index similar to
      the Goldschmidt tolerance factor for perovskite.

PMID- 30198711
TI  - Mononuclear and Dinuclear Ruthenium Complexes of cis- and trans-Thioindigo:
      Geometrical and Electronic Structure Analyses.
AB  - The compounds [Ru(acac)2(L)] (1) and [Ru2(acac)4(MU-L)] (2) with acac- =
      acetylacetonato and L = thioindigo were characterized crystallographically with a
      cis-configurated L and O,O'-coordinated metal in 1 and with trans-configurated L
      and two S,O-coordinated bridged ruthenium centers for 2. The electronic
      structures of 1 and 2 were confirmed by spectroscopy and density functional
      theory calculations, suggesting considerable metal-to-ligand electron transfer
      resulting in the formation of the thioindigo radical anion and oxidized metal(s).
      UV-Vis-Near-IR and IR (spectro)electrochemistry was used to investigate charged
      forms 1 n ( n = 1+, 1-) and 2 n ( n = 1+, 1-, 2-), which reveal electron transfer
      activity of both the metal and the thioindigo ligand as well as sizable orbital
      mixing. An intense near-IR absorption is observed for 2- at 2180 nm. The
      remarkable ligand properties of thioindigo are being discussed in connection to
      related coordination compounds of indigo derivatives such as dehydroindigo and
      corresponding ("Nindigo") diimines.

PMID- 30198712
TI  - Colloidal Synthesis of Double Perovskite Cs2AgInCl6 and Mn-Doped Cs2AgInCl6
      Nanocrystals.
AB  - We show here the first colloidal synthesis of double perovskite Cs2AgInCl6
      nanocrystals (NCs) with a control over their size distribution. In our approach,
      metal carboxylate precursors and ligands (oleylamine and oleic acid) are
      dissolved in diphenyl ether and reacted at 105  degrees C with benzoyl chloride.
      The resulting Cs2AgInCl6 NCs exhibit the expected double perovskite crystal
      structure, are stable under air, and show a broad spectrum white
      photoluminescence (PL) with quantum yield of ~1.6 +/- 1%. The optical properties
      of these NCs were improved by synthesizing Mn-doped Cs2AgInCl6 NCs through the
      simple addition of Mn-acetate to the reaction mixture. The NC products were
      characterized by the same double perovskite crystal structure, and Mn doping
      levels up to 1.5%, as confirmed by elemental analyses. The effective
      incorporation of Mn ions inside Cs2AgInCl6 NCs was also proved by means of
      electron spin resonance spectroscopy. A bright orange emission characterized our
      Mn-doped Cs2AgInCl6 NCs with a PL quantum yield as high as ~16 +/- 4%.

PMID- 30198713
TI  - Metabolomics and Transcriptomics Analyses Reveal Nitrogen Influences on the
      Accumulation of Flavonoids and Amino Acids in Young Shoots of Tea Plant (
      Camellia sinensis L.) Associated with Tea Flavor.
AB  - Tea-specialized metabolites contribute to rich flavors and healthy function of
      tea. Their accumulation patterns and underlying regulatory mechanism are
      significantly different under different nitrogen (N) conditions during adaptation
      stage. Here, we find that flavonoids associated with tea flavor are dominated by
      different metabolic and transcriptional responses among the four N conditions (N
      deficiency, nitrate, ammonia, and nitric oxide). Nitrogen-deficiency tea plants
      accumulate diverse flavonoids, corresponding with higher expression of hub genes
      including F3H, FNS, UFGT, bHLH35, and bHLH36. Compared with N-deficiency, N
      supply tea plants significantly increase proline, glutamine, and theanine, which
      are also associated with tea flavor, especially under NH4+-supply. As NH4+
      tolerant species, tea plant exploits the adaptive strategy by substantial
      accumulation of amino acids including theanine to adapt excess NH4+, which
      attributes to, at least in part, efficient N transport and assimilation, and
      active protein degradation. A distinct divergence of N reallocation in young
      shoots of tea plant under different N sources contributes to diverse tea flavor.

PMID- 30198714
TI  - Computational Prediction and Experimental Realization of p-Type Carriers in the
      Wide-Band-Gap Oxide SrZn1- xLi xO2.
AB  - It is challenging to achieve p-type doping of zinc oxides (ZnO), which are of
      interest as transparent conductors in optoelectronics. A ZnO-related ternary
      compound, SrZnO2, was investigated as a potential host for p-type conductivity.
      First-principles investigations were used to select from a range of candidate
      dopants the substitution of Li+ for Zn2+ as a stable, potentially p-type, doping
      mechanism in SrZnO2. Subsequently, single-phase bulk samples of a new p-type
      doped oxide, SrZn1- xLi xO2 (0 < x < 0.06), were prepared. The structural,
      compositional, and physical properties of both the parent SrZnO2 and SrZn1- xLi
      xO2 were experimentally verified. The band gap of SrZnO2 was calculated using
      HSE06 at 3.80 eV and experimentally measured at 4.27 eV, which confirmed the
      optical transparency of the material. Powder X-ray diffraction and inductively
      coupled plasma analysis were combined to show that single-phase ceramic samples
      can be accessed in the compositional range x < 0.06. A positive Seebeck
      coefficient of 353(4) MUV K-1 for SrZn1- xLi xO2, where x = 0.021, confirmed that
      the compound is a p-type conductor, which is consistent with the pO2 dependence
      of the electrical conductivity observed in all SrZn1- xLi xO2 samples. The
      conductivity of SrZn1- xLi xO2 is up to 15 times greater than that of undoped
      SrZnO2 (for x = 0.028 sigma = 2.53 MUS cm-1 at 600  degrees C and 1 atm of O2).

PMID- 30198715
TI  - A Series of Octahedral First-Row Transition-Metal Ion Complexes Templated by
      Wells-Dawson Polyoxometalates: Synthesis, Crystal Structure, Spectroscopic, and
      Thermal Characterizations, and Electrochemical Properties.
AB  - Three Wells-Dawson polyoxotungstates-based hybrid compounds of general formula
      [M(C3H7NO)6][{M(C3H7NO)5}2(MU-P2W18O62)]. nC3H7NO. n'H2O [with M = MnII (1), FeII
      (2), CoII (3) ; n = 2, 2, 3 and n' = 0, 0, 1, respectively] were synthesized at
      room temperature by a facile method and characterized by IR and 1H and 31P NMR
      spectroscopy studies, thermogravimetric analysis-differential scanning
      calorimetry thermal analyses, UV-vis, X-ray diffraction (XRD) powder and single
      crystal XRD analyses, and cyclic voltammetry studies. From the X-ray study, it
      was established that the metal (M = Mn, Fe, Co) is located on an inversion
      center, being octahedrally coordinated to six dimethylformamide (DMF) molecules
      to form the complex cation [M(dmf)6]2+. Also, in the dinuclear complex anion
      [{M(dmf)5}2(MU-P2W18O62)]2-, the M atoms are coordinated to five DMF molecules
      through the oxygen atoms, while the sixth coordination site is occupied by a
      terminal oxygen atom of the Wells-Dawson anion [P2W18O62]6- that plays the role
      of a bridging ligand. The crystal components are connected through numerous weak
      C-H...O hydrogen bonds to construct a three-dimensional network. The UV-vis shows
      the two characteristic absorption bands for the three compounds at 266-268 and
      297 nm. These two strong bands are attributed to the charge-transfer absorption
      band of Ot-W and Ob/c-W, respectively. Cyclic voltammetry study of compounds (1),
      (2), and (3) reveals at least two reduction reversible peaks ascribed to a Wells
      Dawson cluster.

PMID- 30198716
TI  - Near-Infrared Photoactivatable Nitric Oxide Donors with Integrated Photoacoustic
      Monitoring.
AB  - Photoacoustic (PA) tomography is a noninvasive technology that utilizes near
      infrared (NIR) excitation and ultrasonic detection to image biological tissue at
      centimeter depths. While several activatable small-molecule PA sensors have been
      developed for various analytes, the use of PA molecules for deep-tissue analyte
      delivery and monitoring remains an underexplored area of research. Herein, we
      describe the synthesis, characterization, and in vivo validation of photoNOD-1
      and photoNOD-2, the first organic, NIR-photocontrolled nitric oxide (NO) donors
      that incorporate a PA readout of analyte release. These molecules consist of an
      aza-BODIPY dye appended with an aryl N-nitrosamine NO-donating moiety. The
      photoNODs exhibit chemostability to various biological stimuli, including redox
      active metals and CYP450 enzymes, and demonstrate negligible cytotoxicity in the
      absence of irradiation. Upon single-photon NIR irradiation, photoNOD-1 and
      photoNOD-2 release NO as well as rNOD-1 or rNOD-2, PA-active products that enable
      ratiometric monitoring of NO release. Our in vitro studies show that, upon
      irradiation, photoNOD-1 and photoNOD-2 exhibit 46.6-fold and 21.5-fold
      ratiometric turn-ons, respectively. Moreover, unlike existing NIR NO donors, the
      photoNODs do not require encapsulation or multiphoton activation for use in live
      animals. In this study, we use PA tomography to monitor the local, irradiation
      dependent release of NO from photoNOD-1 and photoNOD-2 in mice after subcutaneous
      treatment. In addition, we use a murine model for breast cancer to show that
      photoNOD-1 can selectively affect tumor growth rates in the presence of NIR light
      stimulation following systemic administration.

PMID- 30198717
TI  - Stability Effects of Protein Mutations: The Role of Long-Range Contacts.
AB  - Predicting the effect of a single point mutation on protein thermodynamic
      stability (DeltaDelta G) is an ongoing challenge with high relevance for both
      fundamental and applicable aspects of protein science. Drawbacks that limit the
      predictive power of stability prediction tools include the lack of
      representations for the explicit energetic terms of the unfolded state. Using
      coarse-grained simulations and analytical modeling analysis, we found that a
      mutation that involves the breaking of long-range contacts may lead to an
      increase in the unfolded state entropy, which can lead to an overall
      destabilization of the protein. A bioinformatics analysis indicates that the
      effect of mutation on the unfolded state is greater for hydrophobic or charged
      (compared with polar) residues that participate in long-range contacts through a
      loop length longer than 18 amino acids and whose formation probabilities are
      relatively high.

PMID- 30198718
TI  - Parasubindoles A-G, Seven Eremophilanyl Indoles from the Whole Plant of
      Parasenecio albus.
AB  - Parasubindoles A-G (1-7), seven eremophilanyl indoles with an unprecedented 12 H
      cyclopentane[ b]naphthalenespiro-1,3'-indole skeleton, were isolated from the
      whole plant of Parasenecio albus. Their structures with absolute configurations
      were elucidated by spectroscopic methods, single-crystal X-ray diffraction, and
      ECD analyses. Plausible biosynthetic pathways of 1-7 were postulated.

PMID- 30198719
TI  - Saturn-Shaped Ice Burst Pattern and Fast Basal Binding of an Ice-Binding Protein
      from an Antarctic Bacterial Consortium.
AB  - Ice-binding proteins (IBPs) bind to ice crystals and control their growth,
      enabling host organisms to adapt to subzero temperatures. By binding to ice, IBPs
      can affect the shape and recrystallization of ice crystals. The shapes of ice
      crystals produced by IBPs vary and are partially due to which ice planes the IBPs
      are bound to. Previously, we have described a bacterial IBP found in the
      metagenome of the symbionts of Euplotes focardii ( EfcIBP). EfcIBP shows
      remarkable ice recrystallization inhibition activity. As recrystallization
      inhibition of IBPs and other materials are important to the cryopreservation of
      cells and tissues, we speculate that the EfcIBP can play a future role as an ice
      recrystallization inhibitor in cryopreservation applications. Here we show that
      EfcIBP results in a Saturn-shaped ice burst pattern, which may be due to the
      unique ice-plane affinity of the protein that we elucidated using the fluorescent
      based ice-plane affinity analysis. EfcIBP binds to ice at a speed similar to that
      of other moderate IBPs (5 +/- 2 mM-1 s-1); however, it is unique in that it binds
      to the basal and previously unobserved pyramidal near-basal planes, while other
      moderate IBPs typically bind to the prism and pyramidal planes and not basal or
      near-basal planes. These insights into EfcIBP allow a better understanding of the
      recrystallization inhibition for this unique protein.

PMID- 30198720
TI  - Protein Knotting by Active Threading of Nascent Polypeptide Chain Exiting from
      the Ribosome Exit Channel.
AB  - The mechanism of folding of deeply knotted proteins into their native structure
      is still not understood. Current thinking about protein folding is dominated by
      the Anfinsen dogma, stating that the structure of the folded proteins is uniquely
      dictated by the amino acid sequence of a given protein and that the folding is
      driven uniquely by the energy gained from interactions between amino acids that
      contact each other in the native structure of the protein. The role of ribosomes
      in protein folding was only seen as permitting the folding to progress from the N
      terminal part of nascent protein chains. We propose here that ribosomes can
      participate actively in the folding of knotted proteins by actively threading
      nascent chains emerging from the ribosome exit channels through loops formed by a
      synthesized earlier portion of the same protein. Our simulations of folding of
      deeply knotted protein Tp0624 positively verify the proposed ribosome-driven
      active threading mechanism leading to the formation of deeply knotted proteins.

PMID- 30198721
TI  - A Bottom-Up Formation Mechanism of Solid Electrolyte Interphase Revealed by
      Isotope-Assisted Time-of-Flight Secondary Ion Mass Spectrometry.
AB  - Understanding the solid electrolyte interphase (SEI) formation mechanism is
      critically important for the performance and durability of lithium-ion batteries.
      However, the details of how SEI builds up into a nanometer-thick layer from
      molecular level reduction reactions on negative electrodes are missing. Here,
      isotope-assisted time-of-flight secondary ion mass spectrometry analyses were
      designed to answer this fundamental question. By investigating the isotope ratio
      profile in SEI during the initial SEI formation cycle, it is discovered that the
      topmost SEI near the electrolyte formed first and the SEI near the electrode
      formed later. This new "bottom-up" SEI growth mechanism was then correlated to
      the electrolyte one-electron and two-electron reduction reaction dynamics, which
      in turn explains the formation of the two-layered organic-inorganic SEI composite
      structure.

PMID- 30198722
TI  - Total Synthesis of Repraesentin F and Configuration Reassignment by a Gold(I)
      Catalyzed Cyclization Cascade.
AB  - The first total synthesis of repraesentin F has been accomplished by a highly
      diastereoselective gold(I)-catalyzed cyclization cascade as the key step. This
      cycloisomerization/Prins-type tandem transformation enabled direct access to the
      atypical tricyclic carbon skeleton of the natural product with the required syn/
      anti/ syn ring fusion. This synthetic effort also allowed reassignment of the
      relative configuration of repraesentin F and determination of its absolute
      configuration.

PMID- 30198723
TI  - Kinetically Determined Phase Transition from Stage II (LiC12) to Stage I (LiC6)
      in a Graphite Anode for Li-Ion Batteries.
AB  - The electrochemical insertion of Li into graphite initiates a series of
      thermodynamic and kinetic processes. An in-depth understanding of this phenomenon
      will deepen the knowledge of electrode material design and optimize rechargeable
      Li batteries. In this context, the phase transition from dense stage II (LiC12)
      to stage I (LiC6) was comprehensively elucidated in a graphite anode via both
      experimental characterizations and first-principles calculations. The results
      indicate that, although the transition from stage II to stage I is
      thermodynamically allowed, the process is kinetically prohibited because Li ions
      tend to cluster into stage compounds rather than form a solid solution.
      Additionally, the phase transitions involve at least three intermediate
      structures (1T, 2H, and 3R) before reaching the LiC6 (stage I) phase. These
      findings provide new insights into the electrochemical behavior of graphite and
      the electrode process kinetics for rechargeable Li batteries.

PMID- 30198724
TI  - Complexity, attention, and choice in games under time constraints: A process
      analysis.
AB  - We test empirically the strategic counterpart of the Adaptive Decision Maker
      hypothesis (Payne, Bettman, & Johnson, 1993), which states that decision makers
      adapt their attention and decision rules to time pressure in predictable ways.
      For 29 normal form games, we test whether players adapt to tightening time
      constraints by reducing their information search and shifting to less
      computationally demanding heuristics, ultimately leading to systematic changes in
      choices. We specify process models of each decision rule, thereby allowing us to
      rank the rules by complexity on the basis of the number of elementary information
      processing units required to execute each rule. The frequency of decision rule
      use conditional on time constraints is estimated using Bayesian latent class
      modeling. Under time pressure, the subject pool displayed a systematic shift
      toward heuristics of less complexity. We observed an increase in nonstrategic
      decision rules (particularly Level 1) and rules that choose the social optimum at
      the expense of more complex rules including the Nash equilibrium. Also, subjects
      are more likely to not acquire information about others' payoffs, thus
      effectively transforming the games into nonstrategic situations. The subjects'
      adaptation to time pressure was efficient in the sense that it did not lead to
      significant payoff losses. (PsycINFO Database Record (c) 2018 APA, all rights
      reserved).

PMID- 30198725
TI  - The Rutgers Alcohol Problem Index: Measurement equivalence among college students
      in the U.S. and Mexico.
AB  - The Rutgers Alcohol Problem Index (RAPI) is widely used to assess alcohol-related
      problems among college students within the U.S. and internationally. Despite its
      wide usage, whether the RAPI similarly assesses alcohol-related problems among
      students in different countries has not been established. We begin to address
      this issue by evaluating responses to the RAPI for measurement equivalence across
      college students in the U.S. (European Americans and Mexican Americans, treated
      as separate groups) and Mexico (Mexicans). Toward this end, we evaluated the RAPI
      for Differential Item Functioning (DIF) within an item response theory framework.
      Our results showed DIF for 6 item severities, all but one of which differed as a
      function of country (U.S. vs. Mexico). Additional analyses showed that using a
      latent RAPI variable with no DIF assumed had no substantive consequences in terms
      of group mean differences and zero-order correlations with self-reported drinking
      behaviors. Similarly, when using observed RAPI scale scores, there were no
      substantive differences in terms of correlations. The observed scale scores,
      however, led to inaccurate mean comparisons. Based on our results, we recommend
      that scholars model the RAPI as a latent variable when conducting analyses.
      (PsycINFO Database Record

PMID- 30198726
TI  - Predictors of anxiety among sexual minority individuals in the Southern US.
AB  - Sexual minority individuals experience a disproportionate burden of mental health
      issues, particularly in less populous cities of the southern United States.
      Unique identity-related stressors may explain these disparities. The current
      study examines relationships between sexual minority stress, identity, and
      anxiety in sexual minority individuals from a small metropolitan area of the
      South. Sexual minority individuals (N = 249) from the Central Savannah River Area
      completed a survey assessing minority stress (i.e., identity-based
      discrimination, internalized homophobia), identity (i.e., outness comfort,
      community connectedness) and history of anxiety as part of a larger lesbian, gay,
      bisexual, transsexual, queer community health needs assessment. All minority
      stress variables were significantly, positively associated with an anxiety
      history whereas community connectedness was significantly, negatively associated
      with anxiety history at the bivariate level. A multiple logistic regression model
      revealed that assault history was significantly associated with increased odds of
      anxiety history, whereas community connectedness was associated with decreased
      odds of anxiety history. These results demonstrate an influence of discriminatory
      experiences on anxiety in sexual minority individuals of the South and the
      protective value of community connectedness. Providers and advocates should work
      at the individual, community, and systemic levels to eliminate lesbian, gay,
      bisexual discrimination and facilitate community involvement, thereby reducing
      mental health disparities. (PsycINFO Database Record (c) 2018 APA, all rights
      reserved).

PMID- 30198727
TI  - Commitment to school and learning among youth in residential care: The role of
      mother and father support and parents' divorce.
AB  - Commitment to school, commitment to learning, and educational expectations have
      been shown to contribute to positive outcomes among youth in the general
      population. However, it is an underexamined phenomenon among youth in care. This
      study examines the contribution of mother and father support and the moderating
      role of parents' marital status to commitment to school and learning among youth
      in residential care settings (RCSs) in Israel. The study was based on the reports
      of a random cluster sample of 1,409 adolescents (Grades 8 to 12) in 16
      educational RCSs for youth from underprivileged backgrounds, who completed
      structured questionnaires. In line with social capital theories, the findings
      showed that, after controlling for youth background characteristics and grades at
      school, both father and mother support were linked positively with youth
      commitment to school and learning among the whole sample. The findings showed
      that although there was a positive significant relationship between father
      support and commitment to school and learning among youth in married-parent
      families, the link was insignificant among adolescent children of divorced
      parents. However, the interaction between divorce and mother support was
      insignificant. These findings highlight the importance of nurturing parent-youth
      relationships in RCSs and suggest circumstances in which father support is at
      risk to be less beneficial to youth in RCSs-a risk that should be considered by
      the care system as a target for prevention and intervention programs. (PsycINFO
      Database Record

PMID- 30198728
TI  - Maternal depression, maltreatment history, and child outcomes: The role of harsh
      parenting.
AB  - The link between maternal depression and negative child outcomes has been well
      established; however, less is known regarding the impact of harsh parenting on
      child outcomes, especially for women living with depressive symptoms and whom
      also experienced child maltreatment. The purpose of this study was to examine
      harsh parenting practices as a mediator in this known association, in order to
      examine factors associated with negative child outcomes and to explore a
      reduction in future transmission of risk. Mediation analyses were conducted with
      2 samples of mother-child dyads at separate time points (child age 6: n = 325;
      and youth age 12: n = 213) using data collected from the Longitudinal Studies of
      Child Abuse and Neglect. Only women who reported a history of childhood
      maltreatment were included in this study. Positive, significant associations were
      found between maternal depressive symptoms and child internalizing and
      externalizing symptoms at both ages. Further, partial mediation was established
      among maternal depressive symptoms, child outcomes, and harsh parenting
      practices. Analyses demonstrated that mothers with depressive symptoms and a
      history of maltreatment reported use of psychological and physical aggression
      with their children (age 6) and youth (age 12). Findings from this study
      bolstered existing research on maternal depression and child outcomes and
      extended current knowledge of the role of harsh parenting for children age 6 and
      youth age 12. (PsycINFO Database Record

PMID- 30198729
TI  - Choosing for you: Diminished self-other discrepancies in financial decisions
      under risk in the elderly.
AB  - Many older adults hold powerful positions in governments and corporate boards
      throughout the world. Accordingly, older adults often have to make important
      financial decisions on behalf of others under risk. Although it is common to
      observe younger adults taking more risks when making financial decisions for
      others, it is unclear if older adults exhibit the same self-other discrepancies.
      Here, we conducted 2 studies (88 and 124 participants, respectively) to examine
      self-other discrepancies in financial decision making under risk in older adults.
      We focused on 3 aspects of financial decision making: loss aversion (a tendency
      to weight potential losses more strongly than potential gains), risk-aversion
      asymmetry (a tendency to be risk-averse for potential gains and risk-seeking for
      potential losses), and risk preferences separately in gain and loss domains.
      Using computational modeling and behavioral economics tasks, we found weaker self
      other discrepancies in older adults (compared with younger adults) across all 3
      aspects. We also replicated the age differences in self-other discrepancies in
      loss aversion across 2 largely nonoverlapping cohorts. Thus, it appears that when
      making financial decisions on behalf of others, older adults, relative to younger
      adults, have a stronger disposition to regard others' financial outcomes as
      important as their own. (PsycINFO Database Record

PMID- 30198730
TI  - "Adult age differences in decision making across domains: Increased discounting
      of social and health-related rewards": Correction to Seaman et al. (2016).
AB  - Reports an error in "Adult age differences in decision making across domains:
      Increased discounting of social and health-related rewards" by Kendra L. Seaman,
      Marissa A. Gorlick, Kruti M. Vekaria, Ming Hsu, David H. Zald and Gregory R.
      Samanez-Larkin (Psychology and Aging, 2016[Nov], Vol 31[7], 737-746). In the
      article, the levels for the effort task were mischaracterized; levels from an
      earlier pilot version of the task were accidentally reported. This error does not
      affect any of the results because the data for the modeling and analyses used the
      correct levels. The only necessary correction is to the text description of the
      task. Please see the erratum for the full description. (The following abstract of
      the original article appeared in record 2016-53592-005.) Although research on
      aging and decision making continues to grow, the majority of studies examine
      decisions made to maximize monetary earnings or points. It is not clear whether
      these results generalize to other types of rewards. To investigate this, we
      examined adult age differences in 92 healthy participants aged 22 to 83.
      Participants completed 9 hypothetical discounting tasks, which included 3 types
      of discounting factors (time, probability, effort) across 3 reward domains
      (monetary, social, health). Participants made choices between a smaller magnitude
      reward with a shorter time delay/higher probability/lower level of physical
      effort required and a larger magnitude reward with a longer time delay/lower
      probability/higher level of physical effort required. Older compared with younger
      individuals were more likely to choose options that involved shorter time delays
      or higher probabilities of experiencing an interaction with a close social
      partner or receiving health benefits from a hypothetical drug. These findings
      suggest that older adults may be more motivated than young adults to obtain
      social and health rewards immediately and with certainty. (PsycINFO Database
      Record

PMID- 30198731
TI  - Memory for faces in old age: A meta-analysis.
AB  - The present meta-analysis investigated the influence of age on face recognition.
      A total of 19 studies with 79 comparisons of younger and older participants were
      included. Analyses revealed small to moderate effects for hits, and large effects
      for false alarms and signal detection theory (SDT) measures. Younger participants
      outperformed older participants on most face recognition measures. Younger
      participants made more hits (gu = 0.31) and fewer false alarms (gu = 0.95) and
      thus had better SDT recognition performance (gu = 1.01) than older participants.
      These effects were largest for young faces, smaller for mixed-age faces, and
      smallest for older faces. Furthermore, older participants used a more liberal
      response criterion, that is, they were more likely to choose a face than younger
      participants (gu = 0.54). Meta-regression analyses revealed that young faces (vs.
      mixed-age faces) and longer retention intervals were associated with greater
      differences between the age groups for hits but not for false alarms. Funnel plot
      and trim-and-fill analyses indicated the presence of a publication bias.
      Theoretical implications for future research and for older people as eyewitnesses
      are outlined. (PsycINFO Database Record

PMID- 30198732
TI  - Age differences in implicit theories about willpower: Why older people endorse a
      nonlimited theory.
AB  - What people believe about their capacity to exert self-control (willpower),
      whether it is a limited or a nonlimited resource, affects their self-regulation
      and well-being. The present research investigated age-related differences in
      people's beliefs-called implicit theories-about willpower. Study 1 (n = 802, age
      range 18-83 years) showed that with higher age people are more likely to believe
      that willpower is a nonlimited resource. Study 2 (n = 423) with younger (age 18
      35 years) and older adults (age 60-98 years) replicated this finding and showed
      that age and a nonlimited willpower theory are related to perceived autonomy on
      demanding tasks (i.e., sense of self-determination), which might explain the age
      related differences in willpower theories. Finally, experimental Studies 3a (n =
      302) and 3b (n = 497) manipulated an autonomous mindset in younger (age 18-35
      years) and older adults (age 60-87 years) and provided evidence for a causal
      effect of perceived autonomy on self-control-beliefs, supporting the proposed
      developmental mechanism. (PsycINFO Database Record

PMID- 30198734
TI  - Long-term antecedents of constraints and mastery: Findings from the Health and
      Retirement Study.
AB  - Whereas it is well established that having a sense of control over one's life
      circumstances facilitates positive aging-related outcomes across adulthood and
      old age, far less is known about what factors contribute to perceived control and
      whether these factors differ across the adult life span. We used longitudinal
      data from the Health and Retirement Study (N = 7,624, M age at 2006 = 67.50
      years, range 50-104, 59% women) to examine whether level of, and time-related
      change in, episodic memory, depressive symptoms, and health (functional
      limitations, self-rated health) predict levels of 2 distinct components of
      perceived control: constraints and mastery. We found that lower levels of memory,
      more depressive symptoms, and less positive self-rated health were each
      associated with higher levels of constraints. Increases in depressive symptoms
      and functional limitations were also associated with higher levels of
      constraints, whereas stability in memory was related to lower levels of
      constraints. Conversely, lower levels of, and declines in, depressive symptoms
      and functional limitations as well as higher self-rated health were associated
      with self-reported higher levels of mastery. We found some evidence to suggest
      that these effects differ across the adult life span. Our findings show that,
      across adulthood and old age, constraints and mastery are shaped by level of, and
      time-related changes in, key domains of functioning. These findings provide
      impetus for future research to target mechanisms and moderators of such
      associations. (PsycINFO Database Record

PMID- 30198733
TI  - The role of cognitive costs, attitudes about aging, and intrinsic motivation in
      predicting engagement in everyday activities.
AB  - Engagement in cognitively demanding everyday activities has been shown to benefit
      cognitive health in later life. We investigated the factors that influence
      engagement, with specific interest in determining the extent to which the costs
      of engaging cognitive resources are associated with intrinsic motivation and,
      ultimately, participation in everyday activities. Older adults (N = 153) aged
      from 65 to 81 years completed a challenging cognitive task, with the costs of
      cognitive engagement-operationalized as the effort required to maintain
      performance-assessed using systolic blood pressure responses (SBP-R). We also
      assessed participation in everyday activities using both 2-year retrospective
      reports and five daily reports over a 5-week period. Structural models revealed
      that lower levels of costs were associated with more positive attitudes about
      aging, which in turn were associated with higher levels of intrinsic motivation.
      Motivation was subsequently predictive of everyday activity engagement, with the
      effect being specific to those activities thought to place demands on cognitive
      resources. The measure of engagement had minimal impact on the nature of the
      observed effects, suggesting that the retrospective and weekly assessments were
      tapping into similar constructs. Taken together, the results are consistent with
      expectations derived from Selective Engagement Theory (Hess, 2014), which argues
      that engagement in demanding activities is related to the cost associated with
      such engagement, which in turn leads to selective participation through changes
      in motivation. (PsycINFO Database Record

PMID- 30198735
TI  - Artificial visual stimuli for animal experiments: An experimental evaluation in a
      prey capture context with common marmosets (Callithrix jacchus).
AB  - Experimenters often use images of real objects to simulate interactions between
      animal subjects or visual stimuli on a touchscreen to test animal cognition.
      However, the degree to which nonhuman animals recognize 2-D images as
      representing the corresponding real objects remains debated. The common marmoset
      monkey (Callithrix jacchus) has been described as a species that spontaneously
      shows natural behaviors to 2-D images, for example, grasping behaviors to insects
      and fear responses to snakes. In this study, we tested 10 monkeys with their
      favorite food item (crickets), 2-D images (a photo and videos of a cricket), and
      a 3-D plastic model to reevaluate marmoset's spontaneous responses to 2-D images
      and to explore which artificial visual stimuli can motivate spontaneous
      interactions. The monkeys showed grasping behavior to the real cricket and the 3
      D plastic model, but to none of the 2-D images. Our experiment suggests that
      depth information is the most important factor eliciting predatory behavior from
      the marmosets, and, therefore, a stimulus produced by a 3-D printer could be a
      good alternative when a spontaneous interaction or a convincing stimulus is
      required. Furthermore, this work serves as a cautionary tale for those using 2-D
      image presentations with marmosets, and perhaps other animal species. (PsycINFO
      Database Record

PMID- 30198736
TI  - Feeling certain: Gut choice, the true self, and attitude certainty.
AB  - Decisions need not always be deliberative. Instead, people confronting choices
      can recruit their gut feelings, processing information about choice options in
      accordance with how they feel about options rather than what they think about
      them. Reliance on feelings can change what people choose, but might this decision
      strategy also impact how people evaluate their chosen options? The present
      investigation tackles this question by integrating insights from the separate
      literatures on the true self and attitude certainty. Four studies support a
      process model by which focusing on feelings (vs. deliberation) in choice causes
      people to see their true selves reflected in those choices (Studies 1 and 2),
      leading to enhanced attitude certainty (Study 3) and advocacy on behalf of that
      attitude (Study 4) while offering robustness checks and accounting for
      alternative explanations throughout. Discussion of these findings highlights the
      opportunity for new insights at the intersection of feeling-focused decision
      making, attitudes, and the true self. (PsycINFO Database Record

PMID- 30198737
TI  - Time-varying social support and time to death in the cardiovascular health study.
AB  - OBJECTIVES: There is a consensus that social connectedness is integral for a
      long, healthy life. However, studies of social support and survival have
      primarily relied on baseline social support measures, potentially missing the
      effects of fluctuations of perceived support over time. This is especially
      important for older adults who experience increased changes in disability. This
      study examined whether among older adults time-varying perceived social support
      was associated with time to death (main effect model of support) and whether time
      varying disability was a modifier (stress-buffering model of support). Gender and
      marital status were also examined as modifiers. METHODS: Older adults in the
      Cardiovascular Health Study (N = 5,201) completed self- report measures of
      demographics and psychological health and clinical risk factors for mortality at
      baseline (1989-1990). Perceived social support and disability were measured from
      baseline through Wave 11 (1998-1999). Cox regression of time to death with time
      varying covariates was performed. RESULTS: Time-varying as well as baseline-only
      perceived social support was associated with greater survival in the unadjusted
      models but not after adjustment. Gender, marital status, and time-varying
      disability were not significant modifiers. CONCLUSIONS: In contrast with the
      previously reported association between baseline individual differences in
      perceived social support and time to death, older adults' baseline-only and
      fluctuating perceptions of perceived support over time were not associated with
      time to death after adjustment for other clinical physical and psychological risk
      factors. Research is needed to identify other relationship factors that may be
      more informative as time-varying predictors of health and longevity in large
      longitudinal data sets. (PsycINFO Database Record (c) 2018 APA, all rights
      reserved).

PMID- 30198741
TI  - Can quality improvement be optional?
AB  - Comments on the article by J. C. Fortney et al. (see record 2018-24946-001)
      describing their relatively unsuccessful efforts to implement improved care for
      patients with complex mood disorders in safety net clinics. It is unusual for
      scientists to submit papers describing their unsuccessful studies and even more
      unusual for journals to publish them. More importantly, Fortney and this journal
      have provided us with an unusually detailed and thoughtful description of many of
      the factors that may have contributed to this result. Few studies actually
      provide this close a look at what was done to implement the desired changes.
      (PsycINFO Database Record

PMID- 30198740
TI  - Journal editing: Reflections on 6 years of collaborative practice.
AB  - In this editorial, the authors reflect on their 6 years of serving as coeditors
      of Families, Systems, and Health. The uncertain and delightful product of these 6
      years is that their relationship transcended personal and professional boundaries
      to evolve into a rich collaborative experience. Leaving this role prompts them to
      reflect on their work, their field, on challenges they faced, and on recurring
      themes. They want to share some of these reflections with journal readers in the
      hope that some of this will benefit readers in their work. (PsycINFO Database
      Record

PMID- 30198739
TI  - Perceived social support, loneliness, and later life telomere length following
      wartime captivity.
AB  - OBJECTIVES: Telomere length (TL) is a robust indicator of cellular aging. TL
      erosion has been associated with exposure to social and traumatic stressors.
      Loneliness and perceived social support are strongly linked to increased
      morbidity and mortality, but have yet to be investigated in relation to TL after
      extreme stress. The present study examined whether loneliness and lack of
      perceived social support following wartime captivity may be associated with TL as
      repatriated prisoners of war (ex-POWs) enter old age and contribute to its
      prediction. METHOD: A cohort of Israeli ex-POWs from the 1973 Yom Kippur War (n =
      83) were assessed. Questionnaires were utilized to assess loneliness and
      perceived social support 18 years after the repatriation (T1), and Southern
      blotting was used to measure TL 24 years later (T2). A zero-order Pearson
      correlation test and a hierarchical regression analysis were utilized in order to
      examine the research questions. RESULTS: Loneliness and lack of perceived social
      support each significantly predicted shorter TL in later life, and together added
      25.8% to the overall explained variance. CONCLUSIONS: This is the first study to
      empirically demonstrate that loneliness and lack of perceived social support in
      early adulthood may be associated with shorter TL during transition to old age in
      a population that has endured extreme stress. Although the study design precludes
      causal inferences, several psychobiological mechanisms may explain the findings.
      The potential clinical significance of social deficits for longevity and heath in
      related populations is therefore addressed, and an agenda for future
      investigations is suggested. (PsycINFO Database Record (c) 2018 APA, all rights
      reserved).

PMID- 30198738
TI  - Identifying targets for cardiovascular medication adherence interventions through
      latent class analysis.
AB  - OBJECTIVE: Reasons for nonadherence to cardiovascular medications vary widely
      between individuals. Yet, adherence interventions are often uniformly applied,
      limiting their effectiveness. This study employed latent class analysis (LCA) to
      identify multidimensional profiles of reasons for nonadherence to cardiovascular
      medications. METHOD: Participants (N = 137; MAge = 58.8, SDAge = 11.8) were drawn
      from an observational study of the impact of cardiac-induced posttraumatic stress
      disorder (PTSD) on cardiac medication adherence in patients presenting to the
      emergency department with a suspected acute coronary syndrome. Demographics and
      depressive symptoms were assessed at baseline. Extent of nonadherence to
      cardiovascular medications, reasons for nonadherence, and PTSD symptoms were
      assessed 1 month after discharge. RESULTS: LCA identified 3 classes of reasons
      for medication nonadherence: capacity (related to routine or forgetting;
      approximately 45% of the sample), capacity + motivation (related to
      routine/forgetting plus informational or psychological barriers; approximately
      14% of the sample), and no clear reasons (low probability of endorsing any items;
      approximately 41% of the sample). Participants reporting greater nonadherence
      were more likely to be in the capacity + motivation or no clear reasons classes
      compared with the capacity class. Participants endorsing higher PTSD severity
      were more likely to be in the capacity + motivation or capacity classes compared
      with the no clear reasons class. CONCLUSIONS: Three distinct classes of reasons
      for nonadherence were identified, suggesting opportunities for tailored
      interventions: capacity, capacity + motivation, and no clear reasons. These
      preliminary findings, if replicated, could aid identification of patients at risk
      for greater extent of medication nonadherence and inform tailored interventions
      to improve adherence. (PsycINFO Database Record (c) 2018 APA, all rights
      reserved).

PMID- 30198742
TI  - Addressing suicide risk in primary care: A next step for behavioral health
      integration.
AB  - Comments on two articles by A. R. Dueweke et al. (see records 2018-24944-001 and
      2018-24945-001). The first article reviews evidence for interventions in primary
      care and the second assesses the ubiquitous two-question "prescreen" of the
      Patient Health Questionnaire-9 (PHQ-9) for detecting patients with thoughts of
      self-harm. In the second article the authors assess the ability of this measure
      to identify thoughts of self harm, the ninth question on the full PHQ-9, and show
      that a substantial number of patients would be missed. These two articles provide
      excellent starting points for thinking through how to ensure that risk of suicide
      is identified and addressed in a systematic and useful way. Any clinician working
      in primary care can use these two articles and the resources they contain to
      inform efforts at systemic change to reduce suicide risk. (PsycINFO Database
      Record

PMID- 30198743
TI  - Scanxiety.
AB  - Scanxiety is a term that has penetrated the vernacular medical vocabulary as a
      descriptor of the particular distress reported by patients who are scheduled for
      imaging to assess disease status. Patients fear failure of current treatments,
      return of disease or progression, the need for new treatments, and the prospect
      of demise. Stress related to imaging is frequent, may be persistent, and is
      linked to decreased quality of life. (PsycINFO Database Record

PMID- 30198744
TI  - Integrated primary care could play a starring role in the Amazon-JP Morgan-Buffet
      health care enterprise.
AB  - Earlier this year, Amazon, J. P. Morgan, and Berkshire Hathaway announced plans
      to launch a joint health care company with more than a million covered lives. Dr.
      Atul Gawande, the prominent Boston-based surgeon and health care thought leader,
      will become the first chief executive officer of this health care venture, with a
      mission to get the best results at the lowest costs and remain free from profit
      making incentives and constraints. In this presidential column, the author
      explores what this has to do with the mission in the Collaborative Family Health
      care Association (CFHA) and the promulgation of integrated health care. (PsycINFO
      Database Record

PMID- 30198745
TI  - Demographic, Parental, and Personal Factors and Youth Athletes' Concussion
      Related Knowledge and Beliefs.
AB  - CONTEXT: : Currently, significant attention is focused on improving care for
      patients with concussions through legislative mandates that include educational
      interventions. Few researchers have examined young athletes' concussion knowledge
      and the factors that may influence their knowledge. OBJECTIVE: : To use the
      socioecological model to examine demographic, parental, and personal factors
      associated with youth athletes' knowledge of concussion. Our ultimate goal is to
      inform the planning and implementation of youth sport concussion-related
      interventions. DESIGN: : Cross-sectional survey. SETTING: : Gymnasium and
      classroom. PATIENTS OR OTHER PARTICIPANTS: : North Carolina and Arizona youth
      athletes (n = 225; age = 8 to 15 years) active in football, boys' or girls'
      soccer, boys' or girls' ice hockey, or boys' or girls' lacrosse in 2012-2013.
      MAIN OUTCOME MEASURE(S): : Participants completed a validated, self-administered
      survey. The intention and belief measures were guided by the theory of planned
      behavior. Perceptions of concussion and intention to seek care were examined
      using descriptive statistics. Athletes' concussion knowledge was modeled using
      linear regressions and generalized estimating equations, with child demographic
      and personal factors and parental knowledge and attitudes about concussion as
      predictors. RESULTS: : Geography, sport, parental attitudes toward concussion,
      and athlete age were associated with athlete knowledge in the univariable
      analyses ( P < .10). In the multivariable model, geographic location (North
      Carolina versus Arizona, mean difference [MD] = 2.2, 95% confidence interval [CI]
      = 1.1, 3.2), sport (girls' soccer versus girls' lacrosse, MD = 2.2, 95% CI = 0.7,
      3.6), more favorable parental attitudes toward concussion (MD = 1.2 for a 2
      standard deviation shift; 95% CI = 0.3, 2.1), and older age (>12 years, MD = 1.6;
      95% CI = 0.5, 2.6) were associated with better knowledge about concussion.
      CONCLUSIONS: : Geographic location, sport, parental attitudes about concussion,
      and athlete's age influenced athletes' concussion-related perceptions, indicating
      the need to address multiple levels of the socioecological model when targeting
      youth sport interventions. Parental interventions that translate to an improved
      culture of youth sport by improving youth athletes' perceptions and experiences
      are key areas for future work.

PMID- 30198746
TI  - Quantitative biodistribution of biotherapeutics at whole body, organ and cellular
      levels by autoradiography.
AB  - AIM: Tools for mapping and quantifying monoclonal antibody (mAb) and peptide
      biotherapeutics distribumtion were evaluated by comparing data from three
      independent methods conducted at the whole body, organ or tissue, and cellular
      levels. MATERIALS & METHODS: [3H]-mAb1 and [3H]-peptide A were administered
      intravenously to rats followed by quantitative whole-body autoradiography, kidney
      macro-autoradiography and micro-autoradiography. RESULTS: [3H]-mAb1 and [3H]
      peptide A concentrations were measured in anatomical regions ranging from whole
      body to whole organ to sub-organ level, such as the kidney glomerulus, with
      increasing resolution. The tissue/blood [3H]-mAb1 concentrations in selected
      kidney microenvironments were comparable among the three quantitative methods.
      CONCLUSION: Quantitative whole-body autoradiography, tissue macro-autoradiography
      and micro-autoradiography all provide useful tools for quantifying the
      concentrations of biotherapeutics at different anatomical levels in tissues,
      facilitating better predictions of efficacy and toxicity.

PMID- 30198748
TI  - Inspiratory muscle training - an inspiration for more effective cardiac
      rehabilitation in heart failure patients?

PMID- 30198747
TI  - A Mouse Model of Delayed Rotator Cuff Repair Results in Persistent Muscle Atrophy
      and Fatty Infiltration.
AB  - BACKGROUND: Rotator cuff (RC) tears are common tendon injuries seen in
      orthopaedic patients. Successful repair of large and massive RC tears remains a
      challenge due to our limited understanding of the pathophysiological features of
      this injury. Clinically relevant small animal models that can be used to study
      the pathophysiological response to repair are limited by the lack of chronic
      repair models. PURPOSE: To develop a highly clinically relevant mouse model of
      delayed RC repair. STUDY DESIGN: Controlled laboratory study. METHODS: Three
      month-old C57BL/6J mice underwent unilateral supraspinatus (SS) and infraspinatus
      (IS) tendon tear with immediate, 2-week delayed, or 6-week delayed tendon repair.
      Animals with no repair or sham surgery served as controls. Gait analysis was
      conducted to measure shoulder function at 2 weeks and 6 weeks after surgery.
      Animals were sacrificed 6 weeks after the last surgery. Shoulder joint, SS, and
      IS muscles were harvested and analyzed histologically. Ex vivo mechanical testing
      of intact and repaired SS and IS tendons was conducted. Reverse-transcriptase
      polymerase chain reaction was performed on SS and IS muscles to quantify atrophy,
      fibrosis, and fatty infiltration-related gene expression. RESULTS: Histological
      and tendon mechanical testing showed that torn tendons could be successfully
      repaired as late as 6 weeks after transection. However, significant atrophy and
      fatty infiltration of muscle, with impaired shoulder function, were persistent in
      the 6-week delayed repair group. Shoulder function correlated with the severity
      of RC muscle weight loss and fatty infiltration. CONCLUSION: We successfully
      developed a clinically relevant mouse model of delayed RC repair. Six-week
      delayed RC repair resulted in persistent muscle atrophy and fatty infiltration
      with inferior shoulder function compared with acute repair. CLINICAL RELEVANCE:
      Our novel mouse model could serve as a powerful tool to understand the
      pathophysiological and cellular/molecular mechanisms of RC muscle and tendon
      degeneration, eventually improving our strategies for treating and repairing RC
      tears.

PMID- 30198750
TI  - Selectivity for quantitation of biomarkers using liquid chromatography and mass
      spectrometry.

PMID- 30198749
TI  - Low-density lipoprotein cholesterol target attainment in patients with stable or
      acute coronary heart disease in the Asia-Pacific region: results from the
      Dyslipidemia International Study II.
AB  - BACKGROUND: As mortality due to cardiovascular disease increases throughout the
      world, accurate data on risk factors such as hyperlipidemia are required. This is
      lacking in the Asia-Pacific region. DESIGN: The observational Dyslipidemia
      International Study (DYSIS) II was established to quantify the extent of
      hyperlipidemia in adults with acute and stable coronary heart disease globally.
      METHODS: Patients with stable coronary heart disease or hospitalised with an
      acute coronary syndrome were enrolled across nine Asia-Pacific countries from
      July 2013 to October 2014. Lipid-lowering therapy and low-density lipoprotein
      cholesterol target attainment (<70 mg/dL) were assessed. The acute coronary
      syndrome cohort was followed up 4 months post-discharge. RESULTS: Of the 4592
      patients enrolled, 2794 had stable coronary heart disease and 1798 were admitted
      with an acute coronary syndrome. In the coronary heart disease cohort, the mean
      low-density lipoprotein cholesterol level was 86.9 mg/dL, with 91.7% using lipid
      lowering therapy and 31% achieving low-density lipoprotein cholesterol of less
      than 70 mg/dL. In the acute coronary syndrome cohort at admission, the
      corresponding values were 103.2 mg/dL, 63.4% and 23.0%, respectively. Target
      attainment was significantly higher in lipid-lowering therapy-treated than non
      treated patients in each cohort (32.6% vs. 12.9% and 31.1% vs. 9.0%,
      respectively). Mean atorvastatin-equivalent dosages were low (20 +/- 15 and 22 +/
      18 mg/day, respectively), with little use of non-statin adjuvants (13.0% and
      6.8%, respectively). Low-density lipoprotein cholesterol target attainment had
      improved by follow-up for the acute coronary syndrome patients, but remained low
      (41.7%). CONCLUSIONS: Many patients in Asia at very high risk of recurrent
      cardiovascular events had a low-density lipoprotein cholesterol level above the
      recommended target. Although lipid-lowering therapy was common, it was not used
      to its full potential.

PMID- 30198751
TI  - Twitter Analysis of #OpenAPS DIY Artificial Pancreas Technology Use Suggests
      Improved A1C and Quality of Life.
AB  - BACKGROUND: Patient-driven innovation in diabetes management has resulted in a
      group of people with type 1 diabetes who choose to build and share knowledge
      around a do-it-yourself (DIY) open source artificial pancreas systems (OpenAPS).
      The purpose of this study was to examine Twitter data to understand how patients,
      caregivers, and care partners perceive OpenAPS, the personal and emotional
      ramifications of using OpenAPS, and the influence of OpenAPS on daily life.
      METHODS: Qualitative netnography was used to analyze #OpenAPS on Twitter over a
      two-year period. RESULTS: There were 328 patients, caregivers, and care partners
      who generated 3347 tweets. One overarching theme, OpenAPS changes lives, and five
      subthemes emerged from the data: (1) OpenAPS use suggests self-reported A1C and
      glucose variability improvement, (2) OpenAPS improves sense of diabetes burden
      and quality of life, (3) OpenAPS is perceived as safe, (4) patient/caregiver
      provider interaction related to OpenAPS, and (5) technology adaptation for user
      needs. CONCLUSIONS: As users of a patient-driven technology, OpenAPS users are
      self-reporting improved A1C, day-to-day glucose levels, and quality of life.
      Safety features important to individuals with diabetes are perceived to be
      embedded into OpenAPS technology. Twitter analysis provides insight on a patient
      population driving an innovative solution to improve their quality of diabetes
      care.

PMID- 30198752
TI  - Recurrence After Arthroscopic Labral Repair for Traumatic Anterior Instability in
      Adolescent Rugby and Contact Athletes.
AB  - BACKGROUND: Traumatic glenohumeral dislocation of the shoulder is one of the most
      common shoulder injuries, especially among adolescent athletes. The treatment of
      instability for young athletes continues to be controversial owing to high
      recurrence rates. PURPOSE: To investigate the recurrence rate of shoulder
      instability after arthroscopic capsulolabral repair for adolescent contact and
      collision athletes. STUDY DESIGN: Case series; Level of evidence, 4. METHODS:
      Sixty-seven patients aged <18 years underwent an arthroscopic labral repair over
      a 5-year period. The mean +/- SD age of the cohort was 16.3 +/- 0.9 years (range,
      14-17 years) and consisted of 1 female and 66 males. All patients were contact
      athletes, with 62 of 67 playing rugby. Demographic, clinical, and intraoperative
      data for all patients with shoulder instability were recorded in our database.
      Recurrence rates were recorded and relative risks calculated. RESULTS: At a
      follow-up of 33 +/- 20 months, 34 of 67 patients had recurrent instability for an
      overall recurrence rate of 51% among adolescent contact athletes after
      arthroscopic labral repair surgery. The mean time to recurrence was 68.1 +/- 45.3
      weeks. All recurrences occurred as a result of a further sporting injury.
      Relative risk analysis demonstrated that athletes aged <16 years had 2.2 (95% CI,
      1.2-2.1) times the risk of developing a further instability episode as compared
      with athletes aged >=16 years at the time of index surgery ( P = .0002). The
      recurrence rate among adolescent athletes after bony Bankart repairs was 57.9%
      versus 47.9% for soft tissue labral repairs ( P = .4698). The incidence of Hill
      Sachs lesions ( P = .0002) and bony Bankart lesions ( P = .009) among adolescent
      athletes was significantly higher than among adult controls ( P = .002). The
      presence of bone loss did not lead to a significant increase in recurrence rate
      over and above the effect of age. CONCLUSION: Adolescent contact athletes
      undergoing arthroscopic labral repair have an overall recurrence rate of 51%.
      Rugby players who undergo primary arthroscopic shoulder stabilization aged <16
      years have 2.2 times the risk of developing a further instability episode when
      compared with athletes aged >=16 years at the time of index surgery, with a
      recurrence rate of 93%.

PMID- 30198754
TI  - The ninth Japan Bioanalysis Forum symposium.
AB  - The ninth Japan Bioanalysis Forum symposium took place at tower hall Funabori,
      Tokyo, Japan, between 6 and 8 February, 2018. Bioanalytical scientists from the
      pharmaceutical industry, CROs, academia and regulatory bodies had many meaningful
      and relevant discussions on current topics of interest in bioanalysis. The 3-day
      symposium featured updated perspectives and experiences on regulated bioanalysis
      of small and large molecules, biomarker measurement and assessment of
      immunogenicity, as well as new areas of bioanalytical validation such as
      quantitative polymerase chain reaction(qPCR) and flow cytometry. There were over
      260 participants from six countries, with 23 oral and 11 poster presentations,
      including the outcomes of Japan Bioanalysis Forum discussion groups. This report
      summarizes the major discussion topics from the conference.

PMID- 30198753
TI  - Growth performance, carcass criteria, and serum biochemical parameters of broiler
      chickens supplemented with either synbiotic or prebiotic under hot climatic
      conditions.
AB  - 1. Two separate experiments were conducted to evaluate the efficacy of either
      prebiotic or synbiotic on growth performance, carcass yield, organ weights, and
      serum metabolic profile of broilers under hot climatic conditions. 2. In
      experiment 1, 150 1-d-old Ross 308 male broiler chickens were fed dietary
      synbiotic (Biomin(r) IMBO, 0, 1 or 1.5 g kg-1 of the starter diets and 0, 0.5 or
      0.75 g kg-1 of the grower diets) for 6 weeks. In experiment 2, 150 1-d-old Ross
      308 male broiler chickens were fed dietary prebiotic (Mannan oligosaccharide 0,
      0.5 or 1 g kg-1 of the starter diets and 0, 0.25 or 0.5 g kg-1 of the grower
      diets) for 6 weeks. Each treatment had 10 replicates containing 5 broiler
      chickens each. 3. Supplementation of synbiotic at 1 or 1.5 g kg-1 feed to broiler
      diets during 1-21 d and 0.5 or 0.75 g kg-1 feed, respectively, during 22-42 d
      improved (P < 0.01) body weight gain, feed conversion ratio (FCR), and decreased
      (P < 0.01) abdominal fat, serum total cholesterol, and low-density lipoprotein
      (LDL) cholesterol levels in experiment 1. 4. Similarly, supplementation of the
      prebiotic at 0.5 or 1 g kg-1 in broiler diets during 1-21 d and 0.25 or 0.50 g kg
      1 feed, respectively, during 22-42 d improved (P < 0.01) body weight gain, FCR,
      and decreased (P < 0.01) abdominal fat, serum cholesterol, and LDL-cholesterol
      levels in experiment 2.

PMID- 30198755
TI  - Estimation of the Withdrawal Time of Levamisole in Eggs after Oral Administration
      to Laying Hens.
AB  - This study was conducted to evaluate withdrawal time of levamisole in eggs after
      oral administration in laying hens at different doses. Sampling of eggs was
      conducted for 37 days after the end of treatment, and levamisole concentrations
      were measured by liquid chromatography-tandem mass spectrometry validated
      according to the Commission Decision 2002/657/EC. Estimated validation parameters
      were as follows: decision limit, 0.54 MUg/kg; detection capability, 0.56 MUg/kg;
      limit of detection, 0.04 MUg/kg; limit of quantification, 0.15 MUg/kg; accuracy
      (recovery), between 92.9 and 102.3%; precision (relative standard deviation),
      <=4.62%; and within-laboratory precision (relative standard deviation), <=5.19%.
      Levamisole residue levels were significantly higher in egg yolks than in egg
      whites. The highest levels of levamisole were detected on day 2 posttreatment in
      groups receiving 50 mg/kg of body weight (556.2 MUg/kg in egg yolks and 166.5
      MUg/kg in egg whites). Significant elimination occurred within 5 days after the
      cessation of treatment in all groups, with an elimination half-life of 1.3 days.
      Levamisole was still detectable on day 30 after the end of treatment in egg
      whites (0.06 MUg/kg) and on day 37 in egg yolks (0.06 MUg/kg). The longest
      withdrawal time for levamisole in eggs (14.9 days) was determined in a group
      treated with 25 mg of levamisole per kg of body weight for two consecutive days.
      According to the results, oral treatment of laying hens with levamisole may
      result in noncompliant egg samples even 14 days after treatment.

PMID- 30198757
TI  - Development and effects of a self-management efficacy promotion program for adult
      patients with congenital heart disease.
AB  - BACKGROUND: With the recent advances in medicine, patients with congenital heart
      disease are surviving to adulthood. Adults with congenital heart disease must
      practice self-management to recognize the symptoms of complications and the
      appropriate response. AIMS: The purpose of this study was to develop a self
      management efficacy promotion program for adults with congenital heart disease
      and to test the effects of the developed program on disease-related knowledge,
      self-management implementation and health-related quality of life. METHODS: A non
      equivalent, control group, pre-post test design was used. The intervention group
      received the self-management efficacy promotion program for six weeks. The
      control group received only the usual care. RESULTS: The study results showed
      that disease-related knowledge ( F=91.095, p<0.001) was significantly different
      between the two groups, as was the self-management performance ( F=11.846,
      p<0.001). However, health-related quality of life (generic core scale: F=0.023,
      p=0.881, cardiac module scale: F=0.174, p=0.678) was not significantly different
      between groups. CONCLUSION: The self-management efficacy promotion program for
      adults with congenital heart disease had a significant effect on disease-related
      knowledge and self-management implementation, but did not affect health-related
      quality of life.

PMID- 30198756
TI  - Prevalence and Molecular Characteristics of Clostridium difficile in Retail
      Meats, Food-Producing and Companion Animals, and Humans in Minnesota.
AB  - Community-associated Clostridium difficile infection (CA-CDI) now accounts for
      approximately 50% of CDI cases in central Minnesota; animals and meat products
      are potential sources. From November 2011 to July 2013, we cultured retail meat
      products and fecal samples from food-producing and companion animals in central
      Minnesota for C. difficile by using standard methods. The resulting 51 C.
      difficile isolates, plus 30 archived local veterinary C. difficile isolates and
      208 human CA-CDI case isolates from central Minnesota (from 2012) from the
      Minnesota Department of Health, were characterized molecularly, and source groups
      were compared using discriminant analysis. C. difficile was recovered from 0 (0%)
      of 342 retail meat samples and 51 (9%) of 559 animal fecal samples. Overall, the
      81 animal source isolates and 208 human source isolates were highly diverse
      genetically. Molecular traits segregated extensively in relation to animal versus
      human origin. Discriminant analysis classified 95% of isolates correctly by
      source group; only five (2.5%) human source isolates were classified as animal
      source. These data do not support meat products or food-producing and companion
      animals as important sources of CA-CDI in the central Minnesota study region.

PMID- 30198758
TI  - Childhood respiratory allergies and symptoms in highly polluted area of Central
      Europe.
AB  - The study investigated the associations between the prevalence of the childhood
      respiratory diseases and the long-term exposure to air pollution in the burdened
      area of Moravian-Silesian Region in the Czech Republic. The health data were
      collected during 2014 in 7,239 children 5, 9, 13 and 17 years of age. Exposure to
      PM10 and NO2 in the residence addresses was based on dispersion models and GIS
      based traffic-related indicators. PM10 levels were positively associated with
      both lifetime (OR 1.35; 95%CI 1.09-1.67) and current (OR 1.32; 95%CI 1.05-1.67)
      allergic rhinitis; current asthma was associated negatively. The associations
      between traffic indicator and respiratory health were not found. On the other
      hand, marked positive associations were found between the respiratory diseases
      and symptom severity structured into ordinal variables, and PM10 and NO2.
      Modelled long-term exposure to air pollution was associated with childhood
      allergic rhinitis and deterioration of the respiratory symptoms.

PMID- 30198759
TI  - A Closer Look at Descriptive Norms and Indoor Tanning: Investigating the
      Intermediary Role of Positive and Negative Outcome Expectations.
AB  - Indoor tanning is a risky behavior that dramatically increases skin cancer risk.
      Researchers from multiple disciplines aim to better understand this behavior to
      develop interventions and messages to curtail it. As such, we investigated the
      role of social norms and outcome expectations as predictors of tanning behavior
      as part of a larger test of constructs included in the Theory of Normative Social
      Behavior. In addition to offering additional empirical results to support
      theoretical claims for the importance of social norms and outcome expectations in
      predicting health behaviors, we offer indoor tanning-specific operationalizations
      in a conditional process model with the aim of assessing how content-specific
      measurements predict indoor tanning intentions. Results of a survey of adult
      indoor tanners from across the U.S. (N = 262) highlight when and how descriptive
      norms influence tanning intentions through the mediating roles of anticipatory
      socialization, injunctive norms, and health threat, and through the moderating
      role of mood-based tanning motivations. Implications for theory building as well
      as for intervention and message design are discussed.

PMID- 30198760
TI  - LC-MS/MS method for denosumab quantitation in human serum with rapid protein
      digestion using immobilized trypsin.
AB  - BACKGROUND: Proteomics-based LC-MS/MS methods using trypsin solution have some
      problems including ion suppression and long protein digestion times. Few
      practical methods to quantify denosumab in human serum have been published.
      METHODOLOGY: Immunoglobulins in serum were extracted using immobilized protein G.
      Denatured, reduced and alkylated serum samples were digested with immobilized
      trypsin for 14 min. A denosumab-unique peptide was identified using a Fourier
      transform mass spectrometer as a signature peptide. The signature peptide was
      quantitated with a hybrid triple-quadrupole/linear ion-trap mass spectrometer.
      CONCLUSION: A rapid and practical proteomics-based LC-MS/MS method using
      immobilized trypsin for denosumab quantitation in human serum was developed. The
      present method has an acceptable analytical performance and can be helpful for
      the determination of serum denosumab in clinical settings.

PMID- 30198762
TI  - Resumes en Francais.

PMID- 30198763
TI  - The Effects of a Text-Centered Literacy Curriculum for Students With Intellectual
      Disability.
AB  - The purpose of this study was to examine the promise and feasibility of a newly
      developed curriculum to teach early literacy skills to students with intellectual
      disability (ID) and students with low IQs. The curriculum texts were written to
      include familiar settings, high frequency words, natural syntax, and cumulative
      practice. A single-case design was used with multiple baseline across levels of
      instruction and included eight participants who had IQs spanning from 40 to 63.
      The study was conducted across one academic year in two private schools for
      students with special needs. Results showed that all eight students demonstrated
      significant growth on proximal measures of taught words, as well as growth on at
      least some curriculum-based distal measures. Additionally, the program was
      demonstrated to be feasible; the teachers implemented the intervention with high
      degrees of fidelity and expressed satisfaction with the effectiveness and
      practicality of the program.

PMID- 30198761
TI  - Pathways from racial discrimination to cortisol/DHEA imbalance: protective role
      of religious involvement.
AB  - OBJECTIVE: Racial discrimination (RD) is hypothesized to dysregulate the
      production of stress reactive hormones among African Americans. Psychological
      processes that may mediate the association between RD and such dysregulation
      (e.g. cortisol/DHEA ratio) are not well articulated. Organizational religious
      involvement (ORI) has been discussed as a psychological protective factor within
      the context of RD, but our understanding of ORI as a physiological protective
      factor remains limited. We evaluated whether RD was directly and indirectly
      (through depressive symptoms) associated with an imbalance of cortisol and DHEA
      hormones, and whether ORI buffered these direct and/or indirect pathways. DESIGN:
      Data were drawn from the Flint Adolescent Study, an ongoing interview study of
      youth that began in 1994. Participants were 188 African American emerging adults
      (47.3% Female, ages 20-22). We used mediation and moderated-mediation analyses,
      as outlined by Hayes [2012. PROCESS SPSS Macro. [Computer Software and Manual].
      http://www.afhayes.com/public/process.pdf ], to evaluate the study aims. RESULTS:
      We found that depressive symptoms mediated the association between RD and the
      cortisol/DHEA ratio. We also found that depressive symptoms mediated the
      association between RD and the cortisol/DHEA ratio for individuals reporting low
      and moderate levels of ORI, but not at high levels. CONCLUSIONS: Our findings
      support the socio-psychobiological model of racism and health [Chae et al. 2011 .
      "Conceptualizing Racial Disparities in Health: Advancement of a Socio
      Psychobiological Approach." Du Bois Review: Social Science Research on Race 8
      (1): 63-77. doi: 10.1017/S1742058X11000166 ] and suggest that the psychological
      toll of RD can confer physiological consequences. Moreover, ORI may disrupt
      pathways from RD to cortisol/DHEA ratio by buffering the psychological toll of
      RD.

PMID- 30198764
TI  - Resumenes al Espanol.

PMID- 30198765
TI  - Evaluation of Pediatrician Adherence to the American Academy of Pediatrics Health
      Supervision Guidelines for Down Syndrome.
AB  - The American Academy of Pediatrics's guideline on health supervision for children
      with Down syndrome (DS) offers pediatricians guidance to improve detection of
      comorbid conditions. Pediatrician adherence has not yet been comprehensively
      evaluated. Medical records of 31 children with DS who received primary care at
      two urban academic clinic sites from 2008-2012 were reviewed. Data was extracted
      on adherence to age-specific individual guideline components for each subject by
      year-of-life (total 84 years-of-life). Overall adherence across all components
      was 83% (2001 guideline) and 67% (2011 guideline). Adherence to thyroid, hearing,
      vision, and developmental components was >85%, and anticipatory guidance
      regarding atlantoaxial instability and sexuality was <35%. Overall adherence was
      higher when a subject was younger and when a provider was an attending-level
      pediatrician.

PMID- 30198766
TI  - Antenatal Hospitalization Among U.S. Women With Intellectual and Developmental
      Disabilities: A Retrospective Cohort Study.
AB  - This population-based retrospective cohort study examines the prevalence of
      hospital utilization during pregnancy and the primary reason for antenatal
      hospital utilization among women with intellectual and developmental disabilities
      (IDD). Massachusetts residents with in-state deliveries that were >= 20 weeks
      gestational age were included via data from the 2002-2009 Massachusetts Pregnancy
      to Early Life Longitudinal Data System. Among women with IDD, 54.8% had at least
      one emergency department (ED) visit during pregnancy, compared to 23% of women
      without IDD. Women with IDD were more likely to have an antenatal ED visit,
      observational stays, and non-delivery hospital stays. This study highlights the
      need for further understanding of the health care needs of women with IDD during
      pregnancy.

PMID- 30198767
TI  - Systematic Review of Interventions Involving Aided AAC Modeling for Children With
      Complex Communication Needs.
AB  - Building the communicative competence of individuals who use augmentative and
      alternative communication (AAC) requires intervention and support. This
      systematic review examined experimental studies involving aided AAC modeling to
      promote the expressive communication of children and youth (i.e., birth to age
      21) with complex communication needs. A search yielded 48 studies involving 267
      participants. Interventions were categorized according to three different
      approaches to aided AAC modeling-augmented input, models as prompts, and models
      within instructional demonstrations. Although the procedures varied,
      interventions were generally effective at improving diverse measures of
      expressive communication. This review provides insight for both researchers and
      practitioners by describing interventions involving three distinct approaches to
      aided AAC modeling, highlighting areas needing future research, and offering
      implications for practice.

PMID- 30198768
TI  - Employment, Income, and SSI Effects of Postsecondary Education for People With
      Intellectual Disability.
AB  - The low employment rates of individuals with intellectual disability (ID) are a
      major concern. This study examined the effect of postsecondary education on
      employment atrnd earnings for individuals with ID and the effect of state
      variation on those outcomes. Rehabilitation Services Administration 911 (RSA-911)
      files for 2008-2013 were analyzed (n = 11,280 individuals with ID). Multilevel
      modeling techniques were used to understand state variation, such as various
      economic and programmatic features that influence outcomes. Postsecondary
      education was associated with increased employment, increased weekly earnings,
      decreased reliance on Supplemental Security Income (SSI) benefits. Policy
      implications are discussed.

PMID- 30198769
TI  - Identifying Needs-Based Groupings Among People Accessing Intellectual Disability
      Services.
AB  - There is increasing emphasis on needs-led service provision for people with
      intellectual disability (ID). This study outlines the statistical cluster
      analysis of clinical data from 1,692 individuals accessing secondary care ID
      services in the United Kingdom (U.K.) Using objective needs assessment data from
      a newly developed ID assessment tool, six clusters were identified. These had
      clinical face validity and were validated using six concurrently (but
      independently) rated tools. In keeping with previous studies, the clusters varied
      in terms of overall level of need as well as specific clinical features (autism
      spectrum disorder, mental health problems, challenging behaviors and physical
      health conditions). More work is now needed to further develop these clusters and
      explore their utility for planning, commissioning and optimizing needs-led
      services.

PMID- 30198770
TI  - Next-generation biomarker discovery in Alzheimer's disease using metabolomics -
      from animal to human studies.
AB  - Alzheimer's disease (AD) is a complex disease driven mainly by neuronal loss due
      to accumulation of intracellular neurofibrillary tangles and amyloid beta
      aggregates in the brain. The diagnosis of AD currently relies on clinical
      symptoms while the disease can only be confirmed at autopsy. The few available
      biomarkers allowing for diagnosis are typically detected many years after the
      onset of the disease. New diagnostic approaches, particularly in easily
      accessible biofluids, are essential. By providing an exhaustive information of
      the phenotype, metabolomics is an ideal approach for identification of new
      biomarkers. This review investigates the current position of metabolomics in the
      field of AD research, focusing on animal and human studies, and discusses the
      improvements carried out over the past decade.

PMID- 30198771
TI  - Branched-Chain Amino Acids Enhance Retinal Ganglion Cell Survival and Axon
      Regeneration after Optic Nerve Transection in Rats.
AB  - PURPOSE: This study's aim was to investigate the beneficial effects of branched
      chain amino acids (BCAAs) on the neuronal survival and axon regeneration of
      retinal ganglion cells (RGCs) after optic nerve (ON) transection. METHOD: The
      experimental rats received daily BCAA injections through the caudal vein after
      left intra-orbital ON transection. Neuroprotection was evaluated by counting
      Fluorogold-labeled RGCs. The role of mammalian target of rapamycin (mTOR) pathway
      activation in promoting RGC survival was studied after rapamycin administration.
      Moreover, a peripheral nerve (PN) graft was transplanted onto the transected ON
      to study the effects of BCAAs on axon regeneration of injured RGCs. RESULTS: Our
      results showed that BCAAs alleviated the death of RGCs 7 and 14 days after ON
      transection, accompanied by an activation of mTOR pathway in RGCs. Blocking mTOR
      pathway with rapamycin eliminated such neuroprotective effects of BCAAs.
      Moreover, BCAAs also promoted axon regeneration of injured RGCs into a PN graft.
      CONCLUSION: Our results suggest a neuroprotection of BCAAs through the activation
      of mTOR pathway. BCAAs also have a beneficial effect on axon regeneration of
      injured RGCs. Therefore, BCAAs could be considered for the clinical treatment of
      ON injury.

PMID- 30198772
TI  - How Does Online Patient-Provider Communication Heal? Examining the Role of
      Patient Satisfaction and Communication Experience in China.
AB  - China is facing the problem of having health care that is difficult to access.
      Online patient-provider communication (OPPC) may bring a new option to deliver
      health services. However, online communication with doctors is still novel to
      many people in China. Little research has been conducted to examine how OPPC
      could improve health outcomes. With an integrated model that incorporates social
      cognitive theory into the three-stage model of health promotion using interactive
      media, this study tested the social mechanism underlying the impact of OPPC.
      Results indicated that self-efficacy, behavioral capability, and outcome
      expectation positively predicted OPPC at Stage 1, which in turn increased patient
      satisfaction at Stage 2, which finally improved three types of health outcomes
      (general, emotional, and physical) at Stage 3. In addition, quality of users'
      experience in OPPC positively moderated this mediation pathway. Theoretical and
      practical implications of this study were also discussed.

PMID- 30198773
TI  - Fruit and VegeTable Intake and Lung Cancer Incidence Among Black Women According
      to Cigarette Smoking Status.
AB  - This project evaluated associations between fruit and vegetable intake, cigarette
      smoking and lung cancer incidence among U.S. Black women. The Black Women's
      Health Study is a prospective cohort study (analytic cohort = 46,889) among Black
      women between the ages 21 and 69 at baseline (1995). Fruit and vegetable intake
      and smoking history were ascertained via questionnaires at baseline and during
      follow-up. Associations between fruit and vegetable intake, smoking and lung
      cancer incidence (N = 306 incident cases through 2013) were evaluated using Cox
      proportional hazards regression. Among women in this cohort, 6.1% and 5.6%
      reported consuming at least three servings/d of fruit or vegetables,
      respectively. Smoking history was associated with increased lung cancer
      incidence. Being a current smoker of >=15 cigarettes/d was associated with higher
      lung cancer incidence compared to never smokers (HR = 17.4, 95% CI: 11.5, 26.4).
      Fruit and vegetable was not associated with lung cancer incidence intake (>=5 vs.
      <3 servings/d, adjusted HR: 0.86, 95% CI: 0.54, 1.36). Associations between fruit
      and vegetable intake and lung cancer incidence did not differ by smoking history.
      Fruit and vegetable intake was low in this study population, but results do not
      support an association between fruit and vegetable intake and lung cancer
      incidence, regardless of smoking history.

PMID- 30198774
TI  - Effectiveness of motivational interviewing to improve oral hygiene in orthodontic
      patients: A randomized controlled trial.
AB  - Maintaining good oral hygiene in patients wearing fixed appliances is a challenge
      for orthodontics. Conventional education has been demonstrated to be insufficient
      for the promotion of good oral habits, while motivational interviewing has the
      potential to facilitate health behavior change. The present randomized controlled
      trial with 130 patients aimed to evaluate the effectiveness of a single session
      of motivational interviewing in enhancing oral hygiene in orthodontic patients
      compared with conventional education alone. Results revealed an immediate
      improvement in oral hygiene which remained stable throughout the 6-month follow
      up.

PMID- 30198775
TI  - Feasibility of Intravenous Iron Isomaltoside to Improve Anemia and Quality of
      Life During Palliative Chemotherapy for Esophagogastric Adenocarcinoma.
AB  - BACKGROUND: Anemia is common with esophagogastric adenocarcinoma, increasing
      mortality, blood transfusions, and reducing quality of life (QOL). No clear
      evidence exists for safe and effective treatment. METHODS: Anemic patients (Hb
      <12 g/dl women, <13 g/dl men) with esophagogastric adenocarcinoma were recruited
      before initiation of palliative chemotherapy. Patients were randomized to
      standard care or single dose of intravenous iron isomaltoside (IVI) before
      chemotherapy. Post-chemotherapy changes in hemoglobin (Hb), ferritin, transferrin
      saturations (TSAT), blood transfusions, and QOL were recorded for three cycles of
      chemotherapy. RESULTS: Twenty-seven patients were randomized to standard care (n
      = 13) or IVI (n = 14). No significant change in Hb was seen (standard care MD 
      0.6 g/dl 95% CI -0.1-1.1 g/dl, P = 0.336; IVI MD +0.5 g/dl 95% CI -0.1-1.1 g/dl,
      P = 0.903). An increase in ferritin was seen with IVI after cycle one of
      chemotherapy (standard care 116 ng/ml; IVI 770 ng/ml, P < 0.05). No difference in
      blood transfusions was seen between groups (P = 0.851). IVI improved QOL with
      physical well-being, emotional well-being, anemia-specific QOL, trial outcome
      index, and total scores all exceeding minimum clinically important difference. No
      improvement was seen with standard care. CONCLUSIONS: This feasibility study
      suggests IVI improves quality of life and ferritin. Larger adequately powered
      studies are required to definitively conclude if hemoglobin and blood transfusion
      changes with IVI.

PMID- 30198776
TI  - How Does Alcohol Consumption Affect Perceptions of One's Own and a Drinking
      Partner's Ability to Consent to Sexual Activity?
AB  - In this naturalistic study, our aim was to examine the extent to which alcohol
      consumption affected perceptions of one's own and one's friend's ability to
      consent to sexual activity. We surveyed 160 adult bargoers in pairs about their
      own and their friends' alcohol consumption, intoxication symptoms, and ability to
      consent to sexual activity. On average, participants reported consuming 4.97
      drinks, rated themselves at the legal limit for driving, reported one
      intoxication symptom, and had a blood alcohol concentration (BAC) just over .08.
      However, few thought they or their friend had diminished cognitive function.
      Accordingly, most indicated that they could consent to sex (93%) and their friend
      could consent to sex (87%). Number of drinks people reported consuming, self
      reported intoxication levels and symptoms, and BACs were significantly
      correlated; however, none of these measures was significantly related to
      individuals' perceptions of their own or their friends' ability to consent to
      sexual activity. Finally, those in man-man pairs were significantly more likely
      than those in woman-woman pairs to indicate they would allow their friend to have
      sex if approached by an interested party. These findings have potential
      implications for prevention programming and for legal cases involving individuals
      who engage in sexual activity while intoxicated.

PMID- 30198777
TI  - Gay Midlife Men's Intergenerational and Interpersonal (Non)Accommodation in the
      Negotiation of HIV Infection Risk: Implications for Sexual Vitality, Generational
      Distinctiveness, and Self-Preservation.
AB  - This study utilizes interview data and a communication accommodation framework to
      explore how early midlife gay men negotiate HIV infection risk vis-a-vis a
      younger gay male sexual culture that has evolved in terms of its regard for
      dangers associated with HIV infection. Analysis of face-to-face interviews with
      33 gay men (aged 40-53) in four U.S. cities revealed a model of gay
      intergenerational sexual (non)accommodation. The model includes forms of
      communicative convergence and nonaccommodating behavior that serve some men's
      achievement or continuation of sexual vitality and/or positive generational
      distinctiveness. Similarities and extensions to communication accommodation
      theory are discussed, as are the model's implications for understanding some gay
      men's management of sexual health at midlife.

PMID- 30198778
TI  - Influence of Norm-Based Messages on College Students' Binge Drinking Intentions:
      Considering Norm Type, Regulatory Mode, and Level of Alcohol Consumption.
AB  - This study examined the influence of norm-based messages on U.S. college
      students' binge drinking intentions, focusing on norm type, locomotion and
      assessment regulatory modes, and level of alcohol consumption as possible
      moderators. Results of an online experiment (N = 519) revealed significant three
      way interactions among regulatory mode (assessment/locomotion), level of alcohol
      consumption, and norm type (i.e., descriptive vs. injunctive norms) on binge
      drinking intentions. The relative persuasiveness of descriptive vs. injunctive
      norm-based messages was contingent upon an individual's locomotion/assessment
      regulatory mode and overall alcohol consumption level. Findings from this study
      extend research on social norms and regulatory mode and provide useful
      suggestions for the norm-based college drinking intervention.

PMID- 30198779
TI  - The Effect of Soy Nut Compared to Cowpea Nut on Body Weight, Blood Cells,
      Inflammatory Markers and Chemotherapy Complications in Children with Acute
      Lymphoblastic Leukemia: A Randomized Controlled Clinical Trial.
AB  - No previous studies were found to examine the effect of soy as a whole food on
      patients with leukemia. The present randomized controlled clinical trial studied
      the effect of soy nut on children with B-cell acute lymphoblastic leukemia (ALL)
      who were in the maintenance phase of chemotherapy. The eligible patients were
      randomized to receive 30 g/day soy or cowpea nut powder for 12 weeks. Dietary
      intake, physical activity, anthropometric measurements, complete blood count,
      serum albumin, serum highly sensitive C-reactive protein (hs-CRP), and Tumor
      necrosis factor alpha (TNF-alpha) as well as chemotherapy side effects were
      assessed at the start and the end of the study. In total 29 and 27 children
      completed the study (aged 6.34 +/- 2.44 and 5.85 +/- 2.35 years) in soy and
      cowpea nut groups, respectively. The total energy and protein intake, and
      physical activity as well as body weight, body mass index, number of red blood
      cells, hemoglobin and hematocrit levels, and fatigue were significantly improved
      in the soy nut group compared to patients who consumed cowpea nut (P < 0.05). Soy
      nut intake might improve the nutritional status, anemia, and fatigue in children
      with ALL. Studies targeting blood cell fractions and disease recurrence are
      highly recommended.

PMID- 30198781
TI  - ESC CardioMed - the new electronic ESC Textbook of Cardiovascular Medicine.

PMID- 30198780
TI  - Differences in Visual Attention Patterns to Sexually Mature and Immature Stimuli
      Between Heterosexual Sexual Offenders, Nonsexual Offenders, and Nonoffending Men.
AB  - Men, whether gynephilic or androphilic, show both early and late attention toward
      adults and not toward children. We examined early and late visual attention to
      sexually mature versus immature stimuli in four groups of heterosexual men:
      sexual offenders against children (SOAC = 18), sexual offenders against adults
      (SOAA = 16), nonsexual offenders (NSO = 18), and nonoffending men (NOM = 19). We
      simultaneously presented adult and child stimuli and measured time to first
      fixation, number of first fixations, total duration of fixation, and fixation
      count to four areas of interest: entire body, then face, chest, and pelvis. We
      found a significant interaction where only SOAC tended to fixate more first times
      to child than to adult stimuli. Conversely, we found longer total duration of
      fixations for the bodies of adults compared to the bodies of children in all
      groups; however, in both the total duration of fixations and the fixation count
      for the whole body, but especially in the chest, SOAC tended to fixate longer and
      more often on child stimuli than the other two groups of offenders, but not
      longer or more often than NOM. This study adds to the limited research using eye
      tracking techniques in samples of SOAC.

PMID- 30198782
TI  - Editor's presentation.

PMID- 30198784
TI  - Foot & Ankle International Achieves Highest Journal Impact Factor Ever.

PMID- 30198785
TI  - Achievable Central Nervous System Concentrations of the Green Tea Catechin EGCG
      Induce Stress in Glioblastoma Cells in Vitro.
AB  - The polyphenolic compounds present in green tea are preventative against cancer
      in several animal tumor models. However, direct cytotoxic effects on cancer cells
      have also been reported. In order to determine whether drinking of green tea has
      chemopreventive or cytotoxic effects on brain cancer cells, we investigated the
      effect of the major green tea polyphenol EGCG as a pure substance and as tea
      extract dietary supplement on primary human glioblastoma cell cultures at the CNS
      achievable concentration of 100 nM reported in the literature. We compared this
      with the effect of the cytotoxic concentration of 500 MUM determined to be
      specific for the investigated primary glioblastoma cultures. After treatment with
      500 uM EGCG, strong induction of autophagy and apoptosis was observed. Under
      treatment with 100 nM EGCG, glioblastoma cells proliferated over the entire
      observation period of 6 days without any detectable signs of cell death. Only
      within the first 12 h of treatment was increased accumulation of autophagic
      vacuoles and increased reactive oxygen species production as a stress response
      demonstrated. Mild forms of stress, such as treatment with 100 nM EGCG, activate
      different endogenous repair mechanisms to protect cells. Our data imply that
      drinking of green tea may have chemopreventive effects, but no direct cytotoxic
      properties.

PMID- 30198786
TI  - Photo-Oxidative Blue-Light Stimulation in Retinal Pigment Epithelium Cells
      Promotes Exosome Secretion and Increases the Activity of the NLRP3 Inflammasome.
AB  - PURPOSE: Age-related macular degeneration (AMD) is a major cause of blindness in
      the elderly, and the activation of the NACHT, LRR, and PYD domain-containing
      protein 3 (NLRP3) inflammasome is involved in AMD pathogenesis. We investigated
      whether photooxidative blue-light stimulation in retinal pigment epithelium (RPE)
      cells promotes exosome secretion and modulates the activity of the NLRP3
      inflammasome in vitro. METHODS: Exosomes were isolated from ARPE-19 cultures
      stimulated or not with blue-light photostimulation (488 nm). Isolated exosomes
      were characterized by transmission electron microscope and Western blot analyses.
      The contents of the NLRP3 inflammasome (IL-1beta, IL-18, and caspase-1 as markers
      of the inflammasome) in exosomes were analyzed by Western blotting. After
      culture, IL-1beta, IL-18, and caspase-1 in RPE cells were analyzed by both
      immunofluorescence and Western blotting. RT-PCR and Western blotting were
      conducted to assess the contents of NLRP3 in RPE cells. RESULTS: Exosomes
      exhibited a typical characteristic morphology (cup-shaped) and size (diameter
      between 50 and 150 nm) in both groups. The exosome markers CD9, CD63, and CD81
      were strongly present. After blue-light photostimulation, ARPE-19 cells were
      noted to release exosomes with higher levels of IL-1beta, IL-18, and caspase-1
      than those in the control group. The levels of IL-1beta, IL-18, and caspase-1 in
      ARPE-19 cells were significantly enhanced when treated with stressed RPE
      exosomes. Additionally, the NLRP3 mRNA and protein levels were found to be
      markedly higher in the treated group than in the control group. CONCLUSIONS:
      Under photooxidative blue-light stimulation, RPE-derived exosomes may aggravate a
      potentially harmful oxidative response through the upregulation of the NLRP3
      inflammasome.

PMID- 30198787
TI  - Five-Year Changes of Anterior Corneal Indices in Diabetics versus Non-Diabetics:
      The Shahroud Eye Cohort Study.
AB  - PURPOSE: To compare 5-year changes of central and peripheral corneal thickness,
      corneal volume, and keratometry between diabetic and non-diabetic individuals
      (>40 years) in a population-based study. MATERIALS AND METHODS: Right eye corneal
      indices of the 333 diabetic persons were compared with 2865 non-diabetics.
      Studied indices included the apical corneal thickness (ACT), minimal corneal
      thickness (MCT), thickness values on corneal rings of 4 mm, 6 mm, and 8 mm in
      diameter, the volume of the 10 mm of the corneal diameter, and the central 3 mm
      keratometry in two steep (Kmax) and flat (Kmin) axes as measured with Pentacam
      (Oculus, Inc, Lynnwood, WA). RESULTS: In the diabetic and non-diabetic groups,
      respectively, the 5-year change was +0.1 +/- 11.9 and -1.2 +/- 11.9 MUm (p =
      0.035) for ACT, -1.1 +/- 12.1 and -2.4 +/- 11.9 MUm (p = 0.056) for MCT, -3.9 +/-
      12.6 and -5.1 +/- 12.3 MUm (p = 0.007) for the 4 mm ring, -5.0 +/- 15.3 and -7.5
      +/- 14.5 MUm (p = 0.006) for the 6 mm ring, and -7.0 +/- 20.1 and -10.8 +/- 19.2
      MUm (p = 0.011) for the 8 mm ring. The diabetic group showed less reduction in
      corneal volume (-0.5 +/- 1.8 mm3) compared to non-diabetics (-0.8 +/- 1.6 mm3) (p
      = 0.030). Kmax (+0.3 +/- 0.5D vs. +0.4 +/- 0.5, p = 0.028) and Kmin (+0.4 +/-
      0.5D vs. +0.5 +/- 0.5, p = 0.005) showed less change in diabetics compared to non
      diabetics. CONCLUSIONS: The overall patterns of change in corneal thickness and
      shape in over 40-year old diabetics are similar to non-diabetics, such that with
      aging, reduced thickness and increased keratometry take the cornea towards a
      prolate shape. However, the age-related changes in central and peripheral corneal
      thickness, volume and corneal shape are less pronounced in diabetic subjects.

PMID- 30198788
TI  - Alpha 2-Adrenergic Receptor Agonist Brimonidine Stimulates ERK1/2 and AKT
      Signaling via Transactivation of EGF Receptors in the Human MIO-M1 Muller Cell
      Line.
AB  - PURPOSE: Alpha 2-adrenergic receptor (alpha2-ADR) agonists are used clinically
      for a range of indications including reducing elevated intraocular pressure in
      patients with open-angle glaucoma or ocular hypertension. Animal experiments show
      that alpha2-ADR agonists attenuate the injury-induced Muller cell
      dedifferentiation by a mechanism that involves activation and regulation of
      extracellular signal-regulated kinase (ERK) 1/2 leading to transactivation of
      epidermal growth factor receptors (EGFRs). The purpose of this study was to study
      and corroborate the activation of this system in human cells. MATERIAL AND
      METHODS: The human Muller cell line MIO-M1 was treated with the alpha2A-ADR
      agonist brimonidine in combination with inhibitors for Src-kinase, EGFR-kinase,
      matrix metalloproteinase (MMP) as well as small interfering RNAs (siRNAs) for the
      EGFR. The cells were analyzed using immunocytochemistry, quantitative PCR and
      western blot techniques. RESULTS: Our results show that human MIO-M1 cells
      express alpha2A-ADRs and that stimulation of these receptors caused a robust
      increase of ERK1/2 and protein kinase B (PKB/AKT) (Thr-308) phosphorylation in
      MIO-M1 cells. P-ERK1/2 and P-AKT (Thr-308) signaling was mediated by Src-kinase
      and associated with phosphorylation of tyrosine residue of epidermal growth
      factor receptor (P-EGFR Y1173). In addition, the agonist caused activation of
      MMPs. These effects could be blocked by Src-kinase inhibitors (PP1, PP2), EGFR
      kinase inhibitor (AG1478), EGFR-siRNA and a MMP inhibitor (GM6001). CONCLUSION:
      The results confirm that this human Muller cell line responds to ADR stimulation
      with phosphorylation of ERK and AKT, which suggests that it is possible to
      pharmacologically target ADR to modulate the early events in human Muller cell
      dedifferentiation in a similar fashion as been shown for chicken Muller cells.
      ABBREVIATIONS: CRALBP: cellular retinaldehyde binding protein; EGFR: epidermal
      growth factor receptor; ERK1/2: extracellular signal-regulated kinase 1/2; GS:
      glutamine synthetase; GPCR: G protein-coupled receptor; IR: immunoreactivity;
      MAPK: mitogen-activated protein kinase; MMP: matrix metalloproteinase; P-ERK1/2:
      phospho-ERK1/2; qRT-PCR: quantitative reverse transcriptase PCR.

PMID- 30198789
TI  - Ceftobiprole medocaril for the treatment of community-acquired pneumonia.
AB  - INTRODUCTION: Ceftobiprole is a novel broad-spectrum cephalosporin with excellent
      activity against a broad range of pathogens that are important in community
      acquired pneumonia (CAP), including drug-resistant pneumococci, methicillin
      resistant Staphylococcus aureus, and Pseudomonas aeruginosa. Areas covered: This
      article reviews the spectrum of activity, the main pharmacological and
      pharmacodynamic characteristics of ceftobiprole as well its clinical efficacy and
      safety in the treatment of CAP in adult patients. Expert opinion: Taking into
      account that the current treatment guidelines for CAP recommend the use of an
      adequate empirical therapy to improve its prognosis, ceftobiprole shows a profile
      of antimicrobial activity that would cover most etiological agents in patients
      with risk factors for infection caused by multidrug resistant organisms. The
      results of the pivotal clinical trial of patients hospitalized with CAP treated
      with ceftobiprole showed a high rate of clinical cure. The clinical tolerance of
      ceftobiprole in clinical trials was generally very good. These findings make
      ceftobiprole a good parenteral therapeutic alternative for the empirical
      treatment of CAP that requires hospitalization, especially in patients with risk
      factors for CAP caused by resistant microorganisms.

PMID- 30198790
TI  - Targeted thrombolysis by using c-RGD-modified N,N,N-Trimethyl Chitosan
      nanoparticles loaded with lumbrokinase.
AB  - Lumbrokinase (LK) has strong fibrinolytic and thrombolytic activities, but it has
      a short half-life, can be easily inactivated, and may cause hemorrhage as a side
      effect. This study develops a potential thrombolytic therapy by fabricating N,N,N
      Trimethyl Chitosan (TMC) nanoparticles modified with the cyclic Arg-Gly-Asp-Phe
      Lys peptide (c-RGD) and loaded with LK (i.e. c-RGD-LK-NPs). The binding of c-RGD
      to platelet membrane GPIIb/IIIa receptors is expected to enable targeted delivery
      of the c-RGD-conjugated TMC to the thrombus. The synthesized c-RGD-LK-NPs had a
      mean particle size of 232.0 nm, zeta potential of 19.8 mV, entrapment efficiency
      of 52.7% +/- 2.5%, and loading efficiency of 17.4% +/- 0.65%. Transmission
      electron microscopy showed that they were generally spherical. The c-RGD-LK-NPs
      gave a cumulative in vitro LK release of 80.6% over 8 h, and the activity of LK
      was close to 80%, indicating that the nanoparticles protected the activity of LK.
      In vitro blood clot lysis assays were carried out and in vivo thrombolysis effect
      was tested in Sprague-Dawley rats carotid artery thrombus model. In all cases,
      the c-RGD-LK-NPs showed superior performance compared with the free LK and the
      unmodified TMC nanoparticles loaded with LK. The c-RGD-LK-NPs reagent is expected
      to be potentially useful in treating thromboembolic diseases.

PMID- 30198791
TI  - Endocrine complications of celiac disease: a case report and review of the
      literature.
AB  - PURPOSE: The purpose of this article is to review recent literature regarding
      endocrine disorders related to celiac disease (CD). METHODS: We describe a case
      report and review existing literature on the endocrine manifestations of CD.
      RESULTS: CD is an autoimmune disorder characterized by intestinal inflammation in
      response to gluten. CD can cause a wide range of extra-intestinal complications,
      including endocrine manifestations. Metabolic bone disease including osteoporosis
      and osteopenia, vitamin D deficiency, secondary hyperparathyroidism and less
      frequently osteomalacia can be seen. In CD, fracture risk is increased by 30-40%,
      while risk for hip fracture is approximately doubled. The risk for other
      endocrine disorders, particularly autoimmune endocrinopathies, is also increased
      in those with CD compared to the general population. Epidemiologic data indicate
      the risk for hypothyroidism is 3-4 times higher among those with CD, while risk
      of type 1 diabetes is greater than double. Risk for primary adrenal insufficiency
      is a striking 11-fold higher in those with versus without CD, though the absolute
      risk is low. Fertility is reduced in women with CD before diagnosis by 37% while
      male fertility in the absence of hypogonadism does not appear to be affected.
      Other endocrine conditions including hyperthyroidism, ovarian failure, androgen
      insensitivity, impaired growth and growth hormone deficiency and autoimmune
      polyendocrine syndromes have also been associated with CD. CONCLUSIONS: CD is
      associated with a wide range of endocrine manifestations.

PMID- 30198792
TI  - Optimization of siRNA delivery to target sites: issues and future directions.
AB  - INTRODUCTION: The discovery of RNA interference (RNAi) earned the 2006 Nobel
      Prize in Physiology or Medicine for its biological significance and potential for
      developing novel therapeutics. The small interfering RNA (siRNA) is the most
      promising tool for translating RNAi to clinical use. Efforts are ongoing to
      improve siRNA delivery through developing novel biomaterials and delivery
      strategies. Given time, it appears that siRNA drugs will eventually become a
      reality. Areas covered: The currently used approaches for siRNA delivery are
      discussed with a focus on siRNA therapeutics currently in clinical testing. A
      comparison of advantageous aspects of currently available platforms and the
      possibility of further optimization for increased efficiency and safety are
      presented. Future directions in siRNA delivery are also highlighted. Expert
      opinion: The recent success in the field of siRNA delivery is based mainly on
      developing new biomaterials with extraordinarily high activities. Notably, the
      introduction of ionizable lipids and novel targeting ligands represent two huge
      steps for realizing siRNA therapy. The currently available systems are largely
      directed to the liver and the new challenge is to extend their applicability for
      treating diseases of other organs. Active targeting to different organs is the
      most promising approach for developing new siRNA-based therapeutics.

PMID- 30198793
TI  - The development of efflux pump inhibitors to treat Gram-negative infections.
AB  - INTRODUCTION: One of the possibilities for reducing the emergence and spread of
      antibiotic resistance is the use of anti-resistance compounds capable of
      resensitizing resistant microorganisms to current antimicrobials. For this
      purpose, multidrug efflux pumps, whose inhibition may increase bacterial
      susceptibility to several antibiotics, including macrolides to which Gram
      negatives are considered intrinsically resistant, have emerged as suitable
      targets. Areas covered: In the current review, the authors discuss different
      mechanisms that can be exploited for inhibiting multidrug efflux pumps and
      describe the properties and the potential therapeutic value of already studied
      efflux pumps inhibitors. Although efforts have already been made to develop these
      inhibitors, there are currently no good candidates for treating infectious
      diseases. Consequently, the authors also discuss potential approaches for their
      development. Expert opinion: Classical anti-resistance drugs such as beta
      lactamases inhibitors, while useful, are only purposeful for treating infections
      caused by beta-lactamase producers. However, inhibitors of multidrug efflux
      pumps, which are present on all organisms, can sensitize both susceptible and
      resistant bacteria to antibiotics belonging to several different structural
      families. Since some efflux pumps are involved in bacterial infections, their
      inhibition may also reduce the infectivity of Gram-negative bacterial pathogens.

PMID- 30198794
TI  - Nomogram Using Optical Coherence Tomography and Visual Field Parameters to
      Predict Brain Lesions in Patients with Bitemporal Hemianopia.
AB  - PURPOSE: This study aims to develop a nomogram to predict brain lesions in
      patients with complete or incomplete bitemporal hemianopia by combining results
      from optical coherence tomography (OCT) and visual field (VF) testing. MATERIAL
      AND METHODS: We reviewed the medical records of patients who underwent magnetic
      resonance imaging (MRI) to identify brain lesions due to bitemporal hemianopia
      between January 2010 and March 2017, retrospectively. The patients were divided
      into two groups based on MRI findings: brain-lesion (+) group that had brain
      lesions on MRI (n = 63), and brain-lesion (-) group without brain lesions on MRI
      (n = 16). We compared OCT and VF findings between the two groups to find factors
      that could predict a brain lesion. Multiple logistic regression analysis was
      performed to select prognostic factors, and we constructed a nomogram to predict
      brain lesions on MRI. RESULT: The VF mean deviation was lower (p = 0.011) and all
      sectors of peripapillary retinal nerve fiber layer thickness except the temporal
      region were thicker in the brain-lesion (+) group. However, there was no
      statistically significant difference in macular ganglion cell-inner plexiform
      layer between the two groups. The area under the receiver operating
      characteristic curve of the nomogram for predicting brain lesions on MRI was
      0.916. CONCLUSION: We developed a nomogram using VF and OCT examinations as a
      novel and accurate screening method to predict brain lesions in patients with
      bitemporal hemianopia and aid ophthalmologists and other clinicians in deciding
      whether to further evaluate a patient by MRI.

PMID- 30198795
TI  - Lipopolysaccharide-induced chorioamnionitis and postnatal lung injury: The
      beneficial effects of L-citrulline in newborn rats.
AB  - AIM OF THE STUDY: The lung architecture of newborns appears to be affected by an
      inflammatory reaction to maternal choriodecidual layer infection. L-citrulline (L
      Cit) was administered to pregnant rats exposed to intra-amniotic
      lipopolysaccharide (LPS)-induced chorioamnionitis to investigate its effect on
      neonatal lung injury. MATERIALS AND METHODS: The pups were assigned to four
      experimental groups: 1- pups exposed to intra-amniotic NaCl but not to postnatal
      L-Cit (Controls); 2 - pups exposed to intra-amniotic NaCl as well as to postnatal
      L-Cit treatment (L-Cit group); 3 - pups exposed to prenatal LPS but not to
      postnatal (LPS); 4- pups exposed to prenatal LPS as well as to postnatal L-Cit
      treatment (LPS + L-Cit). Some pups in each group were sacrificed on postnatal (P)
      day 3 and others on day 7. The pups' lungs were harvested for morphometric
      analysis; cytokine, arginase 1, and VEGF values were quantified. Serum arginine,
      citrulline, asymmetric dimethylarginine (ADMA), symmetric dimethylarginine, NG
      monomethyl arginine, and homoarginine levels were determined using UPLC-MS/MS.
      RESULTS: L-Cit attenuated the disruption of alveolar growth in the LPS + L-Cit
      group. Arginine, homo-arginine, and ADMA levels fell in the LPS treated groups.
      Arginine and ADMA rose at P7 in the L-Cit group whose members also showed higher
      VEGF levels with respect to the Controls. The Controls, instead, showed higher IL
      10 and IL-1beta values with respect to the L-Cit group at P7. Arginase 1 was
      higher in the LPS groups with respect to the Controls at P7. CONCLUSIONS: L-Cit
      improved alveolar and vascular growth diminishing the lung inflammatory response
      in the newborn rats exposed to intra-amniotic LPS. The ADMA/DDAH/NO pathway
      appeared to counteract proinflammatory cytokine production and to sustain
      macrophage migration.

PMID- 30198797
TI  - Tissue microarrays - translational biomarker research in the fast lane.

PMID- 30198796
TI  - Experiences with the levonorgestrel-releasing intrauterine system in Kenya:
      qualitative interviews with users and their partners.
AB  - OBJECTIVES: The levonorgestrel-releasing intrauterine system (LNG-IUS) is an
      underused contraceptive method in sub-Saharan Africa. A recent market assessment
      in Kenya found that if a more affordable version of the method were available it
      may increase demand and uptake of the method. We therefore aimed to examine
      attitudes and perceptions around the LNG-IUS and experiences of method use,
      including exploring attributes such as bleeding changes, contraceptive-related
      amenorrhoea and perceived non-contraceptive benefits. METHODS: Qualitative
      interviews were conducted among 29 women who were current or recent users of the
      LNG-IUS, and among a subset (n = 9) of their husbands/partners. RESULTS: Our
      findings indicate that women's main reason for choosing the LNG-IUS for
      contraception was their perception that the method had fewer side effects
      compared with other contraceptive methods. Women had favourable attitudes towards
      using the LNG-IUS. Husbands were also very positive about their partner's use of
      the method. CONCLUSION: Understanding the motivations and experiences of early
      adopters of the LNG-IUS can help inform the development of demand creation and
      communication strategies to influence uptake and continuation of the LNG-IUS both
      in Kenya and perhaps more broadly. Communication efforts that emphasise the
      positive attributes of the LNG-IUS could help promote wider use of the method,
      especially if new, more affordable product(s) become available.

PMID- 30198798
TI  - Drug-Free Macromolecular Therapeutics Exhibit Amplified Apoptosis in G2/M Phase
      Arrested Cells.
AB  - Drug-free macromolecular therapeutics (DFMT) have been recently developed to
      treat non-Hodgkin lymphoma (NHL). It is a consecutive delivery of two
      nanoconjugates: (1) bispecific engager that pretargets surface CD20, and (2)
      multivalent effector polymer that hybridizes with CD20-bound engagers. Without
      the need of low molecular weight drug, the hybridization of morpholino
      oligonucleotide containing DFMT at NHL cell surface triggers CD20 crosslinking
      and subsequent apoptosis. We have previously determined various factors that
      affect the efficacy of DMFT regarding the synthetic structures. Here, we show
      that DFMT-mediated apoptosis is also influenced by the state of cells. Compared
      with other cell cycle states, cells arrested at G2/M phase exhibit enhanced CD20
      expression, and have more sustainable CD20 binding by DFMT, resulting in a higher
      degree of DFMT-mediated CD20 crosslinking. Moreover, the anti-apoptotic Bcl-2
      protein was phosphorylated in G2/M phase, thereby increasing the cell
      susceptibility to DFMT. As a result, DFMT mediated augmented apoptosis in G2/M
      phase cells. When DFMT was combined with a polymer-docetaxel conjugate that
      triggered G2/M blockage, a combinatorial apoptotic effect was achieved to induce
      programmed cell death. Our findings suggest the co-delivery of DFMT and G2/M
      inhibiting drug combinations may present a therapeutic advantage in NHL
      treatment.

PMID- 30198799
TI  - The FDA Animal Rule and its role in protecting human safety.

PMID- 30198800
TI  - Long-Term Changes in Straylight Induced by Overnight Orthokeratology: An
      Objective Measure Using the Double-Pass System.
AB  - PURPOSE: To map the time course of changes in intraocular straylight of the human
      eye 1 year after initial lens wearing for orthokeratology treatment using the
      objective double-pass technique. MATERIALS AND METHODS: A total of 35 subjects
      (19 males and 16 females) completed the study. The mean age was 11.46 +/- 2.33
      years (range, 8-16 years). All subjects were fitted with spherical four-zone
      orthokeratology lenses following the procedures recommended by the lens
      manufacturer. The subjects were required to wear the lens for at least eight
      consecutive hours at night. After lens removal during the daytime, objective
      scattering index (OSI) was evaluated using the double-pass technique (OQAS-II,
      Visiometrics, Terrassa, Spain) prior to lens dispatch (baseline), followed by
      evaluations at 1 week, 1 month, 6 months, and 12 months after the initial lens
      wearing. Longitudinal changes were fitted to a model containing both an impairing
      and recovery component, and the results were based on an extrapolation between
      the visits. RESULTS: OSI rose quickly following lens wearing, reaching its
      highest level (double that of baseline values) by approximately 1.47 months.
      However, the recovery phase was slow and modest. One year after the initial lens
      wearing, OSI exhibited a 20% recovery from the peak level, but remained 63%
      higher than the baseline level. CONCLUSIONS: Intraocular straylight immediately
      increased flowing lens wearing, and this change reaches maximal level around 1
      month after lens wearing. Slow but significant recoveries of optical quality
      subsequently followed.

PMID- 30198801
TI  - The effects of Antimicrobial Peptides and Hyaluronic Acid compound mask on wound
      healing after ablative fractional Carbon Dioxide laser resurfacing.
AB  - BACKGROUND: Fractional carbon dioxide laser resurfacing (FxCR) is a routine
      treatment of Dermatology while many patients suffered the damage of skin barrier
      function after FxCR. OBJECTIVE: To evaluate the benefits of antimicrobial
      peptides (AMPs) and hyaluronic acid (HA) compound mask on wound healing after
      FxCR on human and mouse skin. METHODS: Twenty-four subjects were treated with
      FxCR on the bilateral cheeks. AMPs and HA compound mask was applied on the FxCR
      treated area of left cheek. The erythema index (EI), melanin index (MI),
      transepidermal water loss (TEWL) of FxCR-treated areas on both cheeks were
      measured. By HE staining, immunohistostaing and western blotting, we analyzed
      epidermal thickness, FLG, IVL expression and protein levels of cramp in FxCR
      treated dorsal mice skin. RESULTS: The EI, MI, and TEWL in the AMPs and HA
      compound mask-treated area of left cheek were significantly lower than those in
      the untreated area of right cheek. Topically application of AMPs and HA compound
      mask reduced thickening of mouse skin and also result in an increase in the
      production of FLG, IVL and cramp. CONCLUSION: Application of AMPs and HA compound
      mask is an effective method for enhancing wound healing after FxCR, by reducing
      transient adverse effects such as erythema, hyperpigmentation, and increased
      TEWL.

PMID- 30198802
TI  - Dabrafenib and trametinib for the treatment of non-small cell lung cancer.
AB  - INTRODUCTION: BRAFV600E mutations occur in 1-2% of lung adenocarcinomas and act
      as oncogenic drivers via the mitogen-activated protein kinase (MAPK) pathway.
      These mutations are mutually exclusive from the more common, epidermal growth
      factor receptor mutations or anaplastic lymphoma kinase rearrangements and have
      been associated with poor outcomes and a lower response to platinum-based
      chemotherapy. Areas covered: Dabrafenib is a potent adenosine-triphosphate
      competitive inhibitor of BRAF kinase and is selective for the BRAFV600E mutation
      in kinase panel screening, cell lines, and xenografts. The efficacy and safety of
      dabrafenib alone or in combination with the MEK inhibitor trametinib has been
      demonstrated in a number of clinical trials and herein, we discuss this data and
      outline the current and future role of BRAF/MEK inhibition in the management of
      advanced lung cancer. Expert commentary: Responses rates with combination of
      dabrafenib/trametinib are approximately 63-64% and interestingly occur in both
      smokers and non-smokers but toxicities require dose reductions in the real world
      for the majority of patients.

PMID- 30198803
TI  - Development of a hydrogen cyanide inhalation exposure system and determination of
      the inhaled median lethal dose in the swine model.
AB  - OBJECTIVE: Cyanide is a highly toxic chemical, and acute exposure depletes cells
      and tissue of oxygen, depressing the respiratory, cardiovascular and neurological
      systems and potentially leading to death. Cyanide has been used as a weapon since
      ancient Rome and continues to pose a potential threat today. A well-characterized
      animal model is necessary for the development of novel methods of rapid detection
      and treatment. This manuscript describes the development of an inhalation
      exposure system designed to evaluate the lethality of acute cyanide inhalation in
      the porcine model. MATERIALS AND METHODS: A custom designed hydrogen cyanide
      (HCN) inhalation exposure system provided stable cyanide concentrations to un
      anesthetized swine while monitoring respiratory parameters. Real-time respiratory
      monitoring, cyanide concentration and body weight were used to calculate inhaled
      doses. RESULTS: The inhalation exposure system generated controlled HCN ranging
      from 260 to 986 ppm to achieve inhaled doses between 1.78 and 3.97 mg/kg. Based
      on survival outcomes, the median lethal dose was determined to be 2.21 mg/kg, and
      the median lethal exposure level was 5893 mg min/m3. DISCUSSION: The ability of
      the HCN inhalation exposure system to deliver target inhaled doses and the
      determination of the inhaled median lethal dose in swine support the use of the
      exposure system and animal model for the evaluation of medical countermeasures of
      acute inhaled HCN toxicity.

PMID- 30198804
TI  - Treating status migrainosus in the emergency setting: what is the best strategy?
AB  - INTRODUCTION: Migraine is a disabling primary headache disorder with unknown
      exact pathomechanism. Status migrainosus (SM) is a complication of migraine (with
      or without aura), representing an attack that lasts for more than 72 h. There is
      a paucity of data published with regard to its pathomechanism and therapeutic
      options. Areas covered: The authors review the literature on SM from PubMed
      published between 1999 and January 2018. The authors specifically look at the
      therapeutic possibilities of SM in the emergency department in patients that have
      or have not already been treated with serotonergic agents. Additional discussion
      is given to the rare complications of migraine. Expert opinion: SM is a
      devastating condition; therefore, the primary goal is to prevent its development
      with proper acute and prophylactic migraine medication. If this treatment fails,
      the patient should be treated in the emergency setting. Due to the severity of
      the condition, parenteral pharmacotherapy is recommended. However, high-quality
      randomized trials are lacking. The currently available data suggest the use of
      intravenous fluids, corticosteroids, magnesium sulfate, anticonvulsive drugs,
      nonsteroidal anti-inflammatory drugs, antiemetics, and serotonergic agents for
      the treatment of SM. Still, there is a need for personalized and causal therapy
      for migraine sufferers.

PMID- 30198805
TI  - An update of clinical experience with the quadrivalent meningococcal ACWY-CRM
      conjugate vaccine.
AB  - INTRODUCTION: Menveo, quadrivalent meningococcal ACWY-CRM conjugate vaccine, was
      first licensed in 2010 in the United States and has a long track record of
      immunogenicity and safety in all age groups, including infants from 2 months of
      age. Areas covered: This review presents clinical and post-marketing experience
      with MenACWY-CRM from 32 studies conducted in 20 countries that included
      individuals aged from 2 months to 75 years. Expert commentary: This decade has
      seen an increased number of countries reporting serogroup W ST-11 clonal complex
      outbreaks of invasive meningococcal disease. As infant vaccination programs
      targeting the meningococcus are reevaluated, the role of quadrivalent
      meningococcal vaccines including MenACWY-CRM will be expanded. MenACWY-CRM was
      immunogenic in all populations and age groups studied, regardless of country of
      origin. MenACWY-CRM can be coadministered with many routinely used infant,
      toddler and adolescent vaccines, and traveler vaccines in adults, allowing for
      flexible use within national immunization programs and recommendations. Antibody
      persistence has been demonstrated up to 5 years post vaccination in all age
      groups. Booster doses induced robust increases in antibody titers for all four
      serogroups, indicative of effective priming and induction of immunological
      memory. The acceptable safety profile of MenACWY-CRM has been confirmed in large
      post-marketing safety studies.

PMID- 30198806
TI  - Validation of the Fitbit Zip and Fitbit Flex with pregnant women in free-living
      conditions.
AB  - Physical activity (PA) is a part of a healthy pregnancy. To date, no consumer
      based activity monitors have been validated with this population. The aim of this
      study was to validate the Fitbit Zip and Fitbit Flex monitors in free-living
      conditions with pregnant women using the ActiGraph GT3X as the ?gold standard?.
      We compared the accuracy of the Fitbit Zip and Fitbit Flex devices in measuring
      steps, sedentary time and time spent in different activity intensities. Sixteen
      women in their third trimester of pregnancy wore the ActiGraph GT3X (hip) plus
      one Fibit Zip (hip) and one Fitbit Flex (wrist) during seven consecutive days.
      The validity of Fitbit Zip and Fitbit Flex is good, depending on measured
      parameters. Fitbit Zip is accurate to measure steps whereas Fitbit Flex is
      precise for MVPA. When choosing between Fitbit Zip and Fitbit Flex monitors,
      pregnant women should take into account their preferred PA and the parameters
      they want to measure..

PMID- 30198807
TI  - Management of severe hemoptysis.
AB  - INTRODUCTION: Though rare, severe hemoptysis (SH) is associated with a mortality
      rate exceeding 50% when not managed properly. Areas covered: This paper reviews
      the recent epidemiological data regarding SH, the role of multidetector computed
      tomography angiography (MDCTA), and fiberoptic bronchoscopy (FOB) in its
      management, as well as the value of current treatments. Expert commentary: MDCTA
      is becoming an essential modality, since it allows determining the location,
      etiology, and mechanism of the bleeding. FOB can be delayed, except when local
      control of bleeding is required. Emergency treatment relies on interventional
      radiology. Both bronchial and non-bronchial arteries should be explored during
      bronchial arteriography. Surgery must be considered in all operable patients if
      the cause of hemoptysis persists.

PMID- 30198809
TI  - Feasibility of an intensive outpatient Perception-Action Approach intervention
      for children with cerebral palsy: a pilot study.
AB  - PURPOSE: The purpose of this pilot study was (1) to evaluate feasibility of
      attendance and parent satisfaction with an intensive outpatient physical and
      occupational therapy program for young children with spastic cerebral palsy (CP)
      and (2) to examine changes in motor function. METHODS: Sixteen children with CP,
      age range 18-36 months (mean 24.3 +/- 6.3 months), received physical and
      occupational therapy sessions (30 minutes each) 5 days per week for 12 weeks.
      Attendance rates and parent satisfaction were assessed. Change in motor function
      using a one-group pre-post design was evaluated using the Gross Motor Function
      Measure-66 (GMFM-66), Quality of Upper Extremity Skills Test, and Pediatric
      Evaluation of Disability Inventory. GMFM-66 outcomes were also compared with
      expected outcomes using previously published normative developmental trajectories
      of children receiving standard therapies. RESULTS: An average of 82% of scheduled
      outpatient physical and occupational therapies for 16 children were completed and
      the 11 parents who completed the Hills and Kitchen's Physiotherapy Outpatient
      Satisfaction Questionnaire were satisfied with the therapies and with their
      child's progress. Participants showed notable, statistically significant
      improvement across all activity-related measures. CONCLUSION: An intensive
      protocol of outpatient therapies utilizing Perception-Action Approach was
      feasible for most families of young children with spastic CP to attend at the
      outpatient clinic location. As this was not an experimental study, no reliable
      conclusions related to efficacy can be made, but the promising results suggest
      that further research into the effectiveness of intensive protocols is
      worthwhile.

PMID- 30198808
TI  - LDL-C does not cause cardiovascular disease: a comprehensive review of the
      current literature.
AB  - INTRODUCTION: For half a century, a high level of total cholesterol (TC) or low
      density lipoprotein cholesterol (LDL-C) has been considered to be the major cause
      of atherosclerosis and cardiovascular disease (CVD), and statin treatment has
      been widely promoted for cardiovascular prevention. However, there is an
      increasing understanding that the mechanisms are more complicated and that statin
      treatment, in particular when used as primary prevention, is of doubtful benefit.
      Areas covered: The authors of three large reviews recently published by statin
      advocates have attempted to validate the current dogma. This article delineates
      the serious errors in these three reviews as well as other obvious falsifications
      of the cholesterol hypothesis. Expert commentary: Our search for falsifications
      of the cholesterol hypothesis confirms that it is unable to satisfy any of the
      Bradford Hill criteria for causality and that the conclusions of the authors of
      the three reviews are based on misleading statistics, exclusion of unsuccessful
      trials and by ignoring numerous contradictory observations.

PMID- 30198811
TI  - Ensuring and Restoring Balance on Access to Controlled Substances for Medical and
      Scientific Purposes: Joint Statement from Palliative Care Organizations.
AB  - The central principle of "balance" represents the dual obligation of governments
      to establish a system of control that ensures the adequate availability of
      controlled substances for medical and scientific purposes while simultaneously
      preventing their nonmedical use, diversion, and trafficking, two primary goals of
      the international control system. On the one hand, although strong opioids,
      including morphine, are absolutely necessary for the relief of severe pain,
      legitimate access to opioids for pain treatment and palliative care is lacking in
      the majority of the world's countries. On the other hand, in a few high-income
      countries with higher consumption of prescription opioids, diversion and
      nonmedical use are increasingly prevalent. This report presents examples of
      unbalanced systems and a joint statement from global and regional palliative care
      organizations to promote development of balanced systems for optimal public
      health outcomes. Although nonmedical use of controlled substances poses a risk to
      society, the system of control is not intended to be a barrier to their
      availability for medical and scientific purposes, nor to interfere in their
      legitimate medical use for patient care. As representatives of palliative care
      organizations, we urge heads of state to act and to take measures to ensure and
      restore balanced systems in their countries and call on public health leaders and
      regulators to work together.

PMID- 30198810
TI  - AKT inhibitor MK-2206 sensitizes breast cancer cells to MLN4924, a first-in-class
      NEDD8-activating enzyme (NAE) inhibitor.
AB  - Breast cancer is a common type of cancer among female cancer patients and the
      main cause of cancer-related deaths. During the last decades, targeted therapies
      for breast cancer have been rapidly developing. Among them, MLN4924, a first-in
      class NEDD8-activating enzyme (NAE) inhibitor, has performed antitumor activity
      by inactivating the cullin-RING ligases and causing the accumulation of their
      substrates to induce apoptosis in a number of studies. In this study, we found
      that MLN4924 activates the AKT pathway in both HER2-positive and triple-negative
      breast cancer (TNBC) cell lines. Given that AKT signaling is responsible for
      tumor progression and drug resistance in some types of cancers, we hypothesized
      that the AKT inhibitor may synergistically enhance the tumor suppression
      capability in breast cancer by MLN4924. To demonstrate the sensitizing effect, MK
      2206 was chosen as the adjuvant treatment, and cell growth, migration and
      apoptosis were detected. The results showed that MLN4924 treatment inhibited cell
      growth and migration and induced apoptosis in both SK-BR3 and MDA-MB231 breast
      cancer cell lines. More importantly, the combined treatment of MLN4924 and MK
      2206 indeed caused stronger cytotoxicity and inhibition of migration and a much
      higher induction of apoptosis compared with MLN4924 treatment alone. Our study
      provides the proof-of-concept evidence for strategic drug combination of MLN4924
      with an AKT inhibitor for maximal killing of breast cancer cells via the
      enhancement of apoptosis.

PMID- 30198812
TI  - Can movement tests predict injury in elite orienteerers? An 1-year prospective
      cohort study.
AB  - The purpose of this study was to determine the predictive value of the movement
      test, the nine test screening battery (9TSB) and an orienteering-modified version
      of the 9TSB (M9TSB), for lower extremity injury in adolescent elite orienteerers.
      Design Prospective cohort study. Participants Forty adolescent (15-19 years),
      male and female orienteerers from two Swedish orienteering high schools performed
      the 9TSB, M9TSB, and recorded injuries based on a web-based questionnaire for 52
      weeks. Results The results showed no difference in composite scores between
      injured and non-injured orienteerers for either 9TSB (p = 0.75) or M9TSB (p =
      0.83). The optimal cut-off score was calculated at 25 for the 9TSB, with
      sensitivity and specificity of 74% and 41% respectively, and 17 for the M9TSB,
      with sensitivity and specificity of 47% and 61%, respectively. There was no
      association between 9TSB or M9TSB and injury (OR1.38, 95% CI: 0.39-4.92).
      Including athletes with a history of injury did not result in improved prediction
      of injury for the 9TSB or M9TSB (OR 2.84, 95% CI: 0.50-16.10). Conclusion Low
      sensitivity and specificity were obtained for both the M9TSB and the 9TSB. Thus,
      it is not recommended that physiotherapists use the nine test screening battery
      to predict lower extremity injury in orienteerers.

PMID- 30198813
TI  - Current and emerging pharmacotherapy for prediabetes: are we moving forward?
AB  - INTRODUCTION: Prediabetes is a state wherein blood glucose levels are above
      normal but below the diagnostic threshold for diabetes. Seventy percent of
      patients with prediabetes develop type 2 diabetes in their lifetime. Despite
      this, prediabetes frequently goes undiagnosed. Areas covered: This review focuses
      on the pharmacological treatment of prediabetes and the prevention of progression
      to diabetes. A literature search was carried out on PubMed and Embase to review
      randomized controlled trials examining treatment of prediabetes. Emerging
      pharmacological therapies with potential benefit are discussed. Expert opinion:
      Lifestyle intervention is the cornerstone for preventing progression to diabetes,
      but metformin remains the first line pharmacological intervention. There appears
      to be minimal additive effect of combining metformin with lifestyle changes. It
      would be interesting to assess whether using combination pharmacological
      approaches plus or minus lifestyle interventions have any additive benefit.
      Despite the good level of evidence available, the penetrance of any interventions
      remains very low in part due to the prodromal categorization of the prediabetic
      state.

PMID- 30198814
TI  - Physical therapy examination and management of a 48-year-old male with vertigo,
      cephalalgia, and cervicalgia secondary to unilateral vestibular hypofunction.
AB  - PURPOSE: This case report presents evidence-based physical therapy assessments
      and interventions for a patient with unilateral vestibular hypofunction (UVH).
      UVH is the result of peripheral vestibular dysfunction in the inner ear. CASE
      DESCRIPTION: The patient was a 48-year-old male with symptoms of dizziness,
      cephalalgia, and cervicalgia. The examination and treatment were focused on
      impaired cervical proprioception, which is a vital component of balance training
      in addition to visual, vestibular, and somatosensory re-education for patients
      with dizziness. Toward the end of the physical therapy episode of care, the
      patient was medically diagnosed with Chiari malformation, a congenital cerebellar
      tonsillar herniation. OUTCOMES: The patient made significant strides on the
      Dizziness Handicap Inventory, Ten Meter Walk Test, Single Leg Stance, Balance
      Error Scoring System, Fukuda Stepping Test, Cervical Joint Position Error Sense
      Test, Convergence Distance, Global Rate of Change, and cervical range of motion
      assessments. The patient did not demonstrate comparable improvements on the
      Dynamic Visual Acuity Test. CONCLUSION: This case report demonstrates a physical
      therapy program for a patient with peripheral UVH-related symptoms. This approach
      may also be applicable for patients with the central cause of dizziness such as
      Chiari malformation. Future directions for research and clinical practice are
      also suggested in this report.

PMID- 30198815
TI  - Mobilization of the lumbar spine in a 76-year-old male with mechanical low back
      pain and an abdominal aortic aneurysm: A case report.
AB  - BACKGROUND: Abdominal aortic aneurysms (AAAs) are found in 1-12% of older males.
      Low back pain (LBP) is prevalent with incidence increasing with age and can
      respond to manual therapy (MT). To date, the safety of the application of MT for
      LBP in the presence of a known AAA has not been reported. This case reports on
      the short-term effects of MT in a patient with LBP and AAA and pre- and post
      therapy imaging. CASE DESCRIPTION: A 76-year-old male presented with mechanical
      LBP, groin pain, and a known 4.2-cm AAA. A lumbar magnetic resonance imaging
      showed significant multilevel abnormalities. Abdominal screening did not elicit
      back or groin pain. Lumbar and hip range of motion and accessory motion testing
      reproduced his complaints. He was treated with lumbar and hip MT. OUTCOMES: After
      three visits, he reported that his groin pain resolved, and his back pain could
      be managed with home exercise. He reported a +6 on the global rating of change.
      Repeated follow-up imaging of his AAA demonstrated no significant change of his
      AAA. DISCUSSION: No immediate adverse events were recorded, and repeated follow
      up imaging indicated no significant AAA expansion. Considering that mobilization
      causes similar displacement to active motion, research into the safety of MT in
      this population is warranted as are guidelines for appropriate initial and
      ongoing clinical screening during treatment in this population.

PMID- 30198817
TI  - Removal of silver nanoparticles coated with different stabilizers from aqueous
      medium by electrocoagulation.
AB  - This study evaluated the removal of silver nanoparticles (AgNPs), coated with
      different stabilizers, from aqueous media using the electrocoagulation technique.
      The AgNPs dispersions were synthesized by chemical reduction with silver nitrate
      as precursor, sodium borohydride as reducing agent and sodium
      carboxymethylcellulose (CMC), polyvinyl alcohol (PVA) and polyvinylpyrrolidone
      (PVP) as stabilizers with initial concentrations of 1 and 3% (w/v). The
      dispersions were named AgNPs-CMC1, AgNPs-CMC3, AgNPs-PVA1, AgNPs-PVA3, AgNPs
      PVP1, and AgNPs-PVP3. Electrocoagulation treatments of AgNPs-PVA1, AgNPs-PVP1 and
      AgNPs-PVP3 dispersions resulted in total silver removals above 99.90% in 10 min.
      For the AgNPs-PVP3 dispersion 99.98% of removal was obtained in 20 min. After 15
      min of electrolysis, The AgNPs-CMC1 and AgNPs-CMC3 dispersions showed a reduction
      in total silver concentration of 71.72 and 52.15%, respectively. Therefore, these
      results showed that the removal of AgNPs from the aqueous medium by
      electrocoagulation is possible, but their efficiency and viability depends on the
      nature, the molecular structure and the concentration of stabilizers.
      Furthermore, the toxicity analysis using the Vibrio fischeri bacteria
      demonstrated that only the dispersions stabilized with PVP became suitable for
      disposal after the electrocoagulation treatment.

PMID- 30198816
TI  - Face-to-trait inferences in patients with Parkinson's disease.
AB  - INTRODUCTION: Parkinson's disease is a progressive neurological disorder
      characterized by the preferential loss of dopaminergic neurons in the substantia
      nigra, which project to the striatum. The disease is characterized by prominent
      motor symptoms, which are its cardinal features. Consequently, Parkinson's
      disease has been primarily considered a disorder of movement. However, increasing
      evidence has indicated that Parkinson's disease affects not only the motor domain
      but also the cognitive domain. Increasing evidence indicates that patients with
      Parkinson's disease have an impaired ability to recognize emotional facial
      expressions. Recent studies have reported that other socially relevant
      information from faces, including face-to-trait inferences for traits such as
      dominance, competence, and trustworthiness, may be processed in subcortical
      regions, including the amygdala and caudate nucleus. However, the mechanism
      underlying the processing of face-to-trait inferences for these traits in
      patients with Parkinson's disease is still unknown. This study aimed to assess
      the face-to-trait inference ability in patients with Parkinson's disease. METHOD:
      Face-to-trait inference ability was assessed using a forced-choice method in
      patients with Parkinson's disease and age- and sex-matched healthy controls.
      RESULTS: Overall correct face-to-trait inferences occurred significantly less
      frequently in the Parkinson's disease group than in the control group. Further
      analysis revealed a significant interaction between groups and the extent to
      which facial features were exaggerated. CONCLUSIONS: The present results suggest
      that the sensitivity of face-to-trait processing was linear in the Parkinson's
      disease group but not in the healthy controls. These deficits may have resulted
      from dysfunction in subcortical regions, which may also lead to impairment in
      other social inferential abilities in patients with Parkinson's disease.

PMID- 30198818
TI  - Interaction of graphene oxide nanoparticles with quartz sand and montmorillonite
      colloids.
AB  - Graphene oxide (GO) nanomaterials are used extensively in a wide range of
      commercial applications. With GO production growing rapidly, it is expected that
      GO eventually could reach sensitive environmental systems, including subsurface
      formations, where montmorillonite, one of the most common minerals, is in
      abundance. This study examines the interaction of GO with quartz sand and
      montmorillonite (MMT) colloids at pH = 7, ionic strength IS = 2 mM, and 25
      degrees C, under dynamic conditions. Moreover, the effect of pH on MMT kinetic
      attachment onto quartz sand was investigated. The experimental data suggested
      that pH affected slightly the attachment of MMT colloids onto quartz sand. GO was
      attached in greater amounts onto MMT than quartz sand. Also, the attachment of GO
      onto quartz sand was shown to increase slightly in the presence of MMT colloids.
      However, when GO and MMT coexisted, the total GO mass attached onto quartz sand,
      suspended MMT, and attached MMT was increased. Furthermore, the equilibrium
      attachment experimental data were fitted nicely with a Freundlich isotherm, and
      the attachment kinetics were satisfactorily described with a pseudo-second-order
      model. Finally, the extended DLVO (XDLVO) theory was used to quantify the various
      interaction energy profiles based on electrokinetic and hydrodynamic
      measurements.

PMID- 30198819
TI  - Prescription Drug Monitoring Programs: Relationships Among Program Awareness,
      Use, and State Mandates.
AB  - The inappropriate use of opioids in the United States has increased markedly and
      has resulted in a tragic loss of lives. To combat this problem, prescription drug
      monitoring programs (PDMPs) have been instituted in most states. Use of the
      programs is voluntary for prescribers in some states, whereas in other states it
      is mandatory. The current study used a self-report survey instrument that was
      administered to 223 participant physicians. The goal of the study was to compare
      awareness and use of the PDMP in a state that mandates use (Ohio) with one that
      does not (North Carolina). Although awareness was not significantly different
      between respondents from the two states, self-reported use was significantly
      higher in the state mandating use (Ohio post-mandate vs. Ohio pre-mandate: 64%
      vs. 51%; chi2 = 15.66, P < .0001; and Ohio post-mandate vs. North Carolina: 64%
      vs. 42%; chi2 = 12.76, P < .0001). Based on these results, mandating use may be
      an effective method to increase PDMP utilization.

PMID- 30198820
TI  - Hfq, a RNA Chaperone, Contributes to Virulence by Regulating Plant Cell Wall
      Degrading Enzyme Production, Type VI Secretion System Expression, Bacterial
      Competition, and Suppressing Host Defense Response in Pectobacterium carotovorum.
AB  - Hfq is a RNA chaperone and participates in a wide range of cellular processes and
      pathways. In this study, mutation of hfq gene from Pectobacterium carotovorum
      subsp. carotovorum PccS1 led to significantly reduced virulence and plant cell
      wall-degrading enzyme (PCWDE) activities. In addition, the mutant exhibited
      decreased biofilm formation and motility and greatly attenuated carbapenem
      production as well as secretion of hemolysin coregulated protein (Hcp) as
      compared with wild-type strain PccS1. Moreover, a higher level of callose
      deposition was induced in Nicotiana benthamiana leaves when infiltrated with the
      mutant. A total of 26 small (s)RNA deletion mutants were obtained among a
      predicted 27 sRNAs, and three mutants exhibited reduced virulence in the host
      plant. These results suggest that hfq plays a key role in Pectobacterium
      virulence by positively impacting PCWDE production, secretion of the type VI
      secretion system, bacterial competition, and suppression of host plant responses.

PMID- 30198821
TI  - Rehabilitation for a complex patient following cerebellar hemorrhage and
      obstructive hydrocephalus: A case report.
AB  - BACKGROUND AND PURPOSE: Inpatient rehabilitation facilities play an integral role
      in patient progress post-stroke. Cerebellar hemorrhages are an infrequent type of
      stroke and are therefore less discussed in the literature; however, inpatient
      rehabilitation continues to be an integral part of patient recovery. The purpose
      of this case report is to discuss the physical therapy interventions, challenges,
      and successes for a complex patient with a large cerebellar hemorrhage with
      obstructive hydrocephalus. CASE DESCRIPTION: The patient is a 32-year-old male
      admitted to an inpatient rehabilitation facility. Prior to admission, the patient
      spent 1 month at a local hospital following a complicated recovery status post
      cerebellar hemorrhage with obstructive hydrocephalus. INTERVENTIONS: The patient
      participated in at least 3 hours of combined therapy a day, split into 30- and 60
      min sessions, and divided between physical, occupational, and speech therapy.
      Physical therapy interventions focused on various gait and coordination
      activities. OUTCOMES: The patient spent 47 days in an inpatient rehabilitation
      facility and demonstrated improvements in all aspects of the Functional
      Independence Measure(r). The patient improved from an 18 to a 90 on the total
      FIM(r) score, allowing the patient to ultimately be discharged home with family
      able to provide 24/7 supervision.

PMID- 30198822
TI  - First Report of Colletotrichum acutatum Causing Flower Anthracnose on Pomegranate
      (Punica granatum) in Southern Brazil.

PMID- 30198823
TI  - Entrainment enhances theta oscillations and improves episodic memory.
AB  - Neural oscillations in the theta band have been linked to episodic memory, but it
      is unclear whether activity patterns that give rise to theta play a causal role
      in episodic retrieval. Here, we used rhythmic auditory and visual stimulation to
      entrain neural oscillations to assess whether theta activity contributes to
      successful memory retrieval. In two separate experiments, human subjects studied
      words and were subsequently tested on memory for the words ('item recognition')
      and the context in which each had been previously studied ('source memory').
      Between study and test, subjects in the entrainment groups were exposed to
      audiovisual stimuli designed to enhance activity at 5.5 Hz, whereas subjects in
      the control groups were exposed to white noise (Expt. 1) or 14 Hz entrainment
      (Expt. 2). Theta entrainment selectively increased source memory performance in
      both studies. Electroencephalography (EEG) data in Expt. 2 revealed that theta
      entrainment resulted in band-specific enhancement of theta power during the
      entrainment period and during post-entrainment memory retrieval. These results
      demonstrate a direct link between theta activity and episodic memory retrieval.
      Targeted manipulation of theta activity could be a promising new approach to
      enhance theta activity and memory performance in healthy individuals and in
      patients with memory disorders.

PMID- 30198824
TI  - Framing genetically modified mosquitoes in the online news and Twitter:
      Intermedia frame setting in the issue-attention cycle.
AB  - We investigate how the online news and Twitter framed the discussion about
      genetically modified mosquitoes, and the interplay between the two media
      platforms. The study is grounded in the theoretical frameworks of intermedia
      agenda setting, framing, and the issue-attention cycle and combines methods of
      manual and computational content analysis, and time series analysis. The findings
      show that the Twitter discussion was more benefit-oriented, while the news
      coverage was more balanced. Initially, Twitter played a leading role in framing
      the discussion about genetically modified mosquitoes. When the public learned
      about the issue, online news gained momentum and led the Twitter publics to
      discuss the risks of genetically modified mosquitoes. Based on the findings, we
      argue that the intermedia frame setting may change its direction over time, and
      different media outlets may be influential in leading different aspects of the
      conversation.

PMID- 30198825
TI  - Is sports science answering the call for interdisciplinary research? A systematic
      review.
AB  - Sports science research is traditionally monodisciplinary despite calls for an
      interdisciplinary focus. The primary purpose of this systematic review was to
      identify studies on talent identification, talent selection and competition
      performance to determine whether interdisciplinary research is being conducted.
      Thirty-six studies met the selection criteria. These studies were critiqued
      relative to sport, skill level, sport science sub-disciplines included, and
      whether the research was multidisciplinary or interdisciplinary. The secondary
      purpose of the review was to critique the level of analysis and level of
      representative task design in performance tests used in the studies. Twenty-five
      studies were categorised as interdisciplinary, with 11 categorised as
      multidisciplinary. Thirteen sports were represented with soccer the most frequent
      followed by field hockey, Australian Rules football, handball and rugby league.
      Thirty-two studies completed their analysis at a group level and four at an
      individual level. A total of 337 performance tests were rated for representative
      task design with 64 categorised as low, 123 as medium and 150 as high. The
      results pertaining to interdisciplinary studies and individual analyses are
      discussed in relation to constraints theory, which predicts that interacting
      variables can explain sport performance. Sports science research is beginning to
      fulfil the call for interdisciplinary research. Future research, however, needs
      to consider individual analyses and representative task design of tests to
      progress sports science knowledge.

PMID- 30198826
TI  - The importance of comorbidities in ischemic stroke: Impact of hypertension on the
      cerebral circulation.
AB  - Comorbidities are a hallmark of stroke that both increase the incidence of stroke
      and worsen outcome. Hypertension is prevalent in the stroke population and the
      most important modifiable risk factor for stroke. Hypertensive disorders promote
      stroke through increased shear stress, endothelial dysfunction, and large artery
      stiffness that transmits pulsatile flow to the cerebral microcirculation.
      Hypertension also promotes cerebral small vessel disease through several
      mechanisms, including hypoperfusion, diminished autoregulatory capacity and
      localized increase in blood-brain barrier permeability. Preeclampsia, a
      hypertensive disorder of pregnancy, also increases the risk of stroke 4-5-fold
      compared to normal pregnancy that predisposes women to early-onset cognitive
      impairment. In this review, we highlight how comorbidities and concomitant
      disorders are not only risk factors for ischemic stroke, but alter the response
      to acute ischemia. We focus on hypertension as a comorbidity and its effects on
      the cerebral circulation that alters the pathophysiology of ischemic stroke and
      should be considered in guiding future therapeutic strategies.

PMID- 30198827
TI  - Quantification of Agrobacterium vitis from Grapevine Nursery Stock and Vineyard
      Soil using Droplet Digital PCR.
AB  - Current detection methodologies for Agrobacterium vitis, causing crown gall of
      grapevines, are time intensive and lack the ability to quantify pathogen
      abundance in nursery stock and soil. Information on pathogen abundance is a key
      component to develop management strategies. The aim of this study was to develop
      a rapid and sensitive quantification assay for grapevine nursery stock and
      vineyard soil via droplet digital polymerase chain reaction targeting the virA
      gene. DNA isolated from roots of dormant grapevines originating from nurseries in
      Germany, California, and Ontario were tested for virA abundance. Bacterial
      numbers varied with grapevine origin; plants from California had the highest
      numbers. In addition, rhizosphere soil from two vineyards in the Okanagan valley
      in British Columbia was tested over a growing season. Sampling time during the
      season did not affect virA gene abundance. The older vineyard had higher soil A.
      vitis populations than the younger vineyard. The assay developed here has
      potential for use in national clean plant programs to prevent import of infected
      grapevine nursery stock and to test vineyard soil for abundance of the pathogen
      before planting.

PMID- 30198828
TI  - Effects of Yeast (1,3)-(1,6)-Beta-Glucan on Severity of Upper Respiratory Tract
      Infections: A Double-Blind, Randomized, Placebo-Controlled Study in Healthy
      Subjects.
AB  - OBJECTIVES: Each year, adults suffer about two to four upper respiratory tract
      infections (URTIs), mostly in winter. The aim of the study was to evaluate the
      effects of brewers' yeast (1,3)-(1,6)-beta-glucan on incidence and severity of
      upper respiratory tract infections (URTIs). METHODS: Generally healthy men and
      women (n = 299) reporting at least three URTIs during the previous year were
      randomized to receive either a placebo or 900 mg of yeast beta-glucan daily for
      16 weeks during winter. In cases of acute URTI, the severity of URTI symptoms was
      assessed via the WURSS-21 questionnaire and the Jackson scale, and a clinical
      confirmation was implemented by the investigator. RESULTS: Overall, 70 subjects
      under placebo and 71 subjects under yeast beta-glucan experienced at least one
      clinically confirmed URTI episode. The global severity using WURSS-21 had been
      quite similar between the study groups (p = 0.5267), whereas during the first
      days of URTIs the severity was less pronounced in the yeast beta-glucan group. On
      the episode level, the severity of physical symptoms was significantly lower for
      all investigated time intervals up to 7 days under yeast beta-glucan (WURSS (Q2
      11) (days 1-2: p = 0.0465, days 1-3: p = 0.0323, days 1-4: p = 0.0248, days 1-7:
      p = 0.0278), also confirmed for the Jackson scale). The reduction of severity was
      accompanied by a significant increase in the joy subscore of the Perceived Stress
      Questionnaire (PSQ20) (p = 0.0148). In addition, there was a reduction of
      systolic (p = 0.0458) and diastolic (p = 0.1439) blood pressure. CONCLUSION:
      Subjects supplementing with yeast beta-glucan benefit by a reduced severity of
      physical URTI symptoms during the first week of an episode, even though the
      incidence and global severity of common colds could not be altered in comparison
      to placebo. Furthermore, accompanying benefits in terms of blood pressure and
      mood were identified. Altogether, yeast beta-glucan supports the immune function.

PMID- 30198829
TI  - Pathways to and Results of Psychiatric Consultation for Patients Referred from
      the Emergency Department. Are there Differences between Migrant and Native
      Patients?
AB  - The aim of this study was to compare migrants and native Italians on the pathways
      to care and results of psychiatric consultation (PC) in the emergency department
      (ED). Patients who were referred from the ED for psychiatric consultation (EDPC)
      at the Maggiore della Carita Hospital between March 2008 and March 2015 were
      recruited consecutively. Socio-demographic, clinical and consultation variables
      were recorded along with information about suicidal behaviours; migrants ( n =
      379; 42.74% males, 57.26% females; age: 45.38 +/- 16.95 years) were compared with
      native Italians ( n = 2942; 43.51% males, 56.49% females; age: 42.08 +/- 15.89
      years). Migrants were younger, more likely to be unemployed and less likely to be
      already under the care of a psychiatrist. Symptoms related to use of alcohol or
      substances were more frequent in migrants, especially female migrants. Migrants
      were less likely than native Italians to be referred for PC because of the
      presence of psychiatric symptoms, however they were more likely to be referred
      because of self-harming behaviour. Nonetheless, migrant status was not identified
      as a risk factor for suicidal behaviour in the multivariate analysis. The outcome
      of EDPC showed differences between migrants and natives. In absolute terms
      migrants were less likely to be admitted to a psychiatric ward after the EDPC
      than native Italians, while they were more likely to be monitored in the ED
      before being discharged or referred to outpatient care. In a high percentage of
      psychiatric examinations of migrants, no psychiatric symptoms were identified.
      Further studies are warranted to disentangle the meaning of these findings.

PMID- 30198830
TI  - Plasma fibrinogen level as possible prognostic biomarker in diffuse large B-cell
      lymphoma.
AB  - OBJECTIVES: Although many studies have assessed numerous molecular and
      immunohistochemical prognostic markers for diffuse large Bcell lymphoma (DLBCL),
      there is always a need for simple widely available markers. This study was
      planned to illustrate the clinical significance of baseline plasma fibrinogen
      levels in DLBCL patients. METHODS: We prospectively investigated 76 DLBCL
      patients treated with rituximab plus cyclophosphamide, vincristine, doxorubicin
      and hostacortine between August 2015 and February 2018. Baseline plasma
      fibrinogen level was measured and correlated with patients' clinical features,
      laboratory parameters, response to therapy, progression-free survival and overall
      survival. RESULTS: Significant association between fibrinogen level and clinical
      features such as the presence of B symptoms (P < .001) and clinical stage (P <
      .001) was observed while no association with age, gender, number of involved
      extranodal sites, performance status and international prognostic index (IPI) was
      found. Baseline fibrinogen level was significantly related to laboratory
      parameters including red cell distribution width (RDW) (P < .001), platelet count
      (P = .02), serum lactate dehydrogenase (LDH) (P = .009) and B2-microglobulin (P =
      .008). No statistically significant correlations were detected between baseline
      fibrinogen levels; and response to therapy, progression-free survival and overall
      survival. CONCLUSION: Baseline plasma fibrinogen level did not show prognostic
      significance for DLBCL patients, although it was associated with patients'
      clinical features and laboratory parameters. Being simple, cheap and widely
      available laboratory test, its use should be encouraged routinely in clinical
      practice to precisely clarify its predictive merit.

PMID- 30198831
TI  - Transvaginal Radiofrequency Ablation of Myomas: Technique, Outcomes, and
      Complications.
AB  - OBJECTIVES: The aim was to study technique, complications, and outcomes of
      transvaginal ultrasound-guided radiofrequency myolysis (TRFAM) of uterine myomas.
      MATERIALS AND METHODS: A prospective observational study of 205 patients with
      metrorrhagia secondary to type II/III submucosal or intramural cavity-distorting
      myomas undergoing outpatient TRFAM under sedation between September 2015 and
      February 2017. MAIN OUTCOME MEASURES: Intraoperative and postoperative
      complications, correction of metrorrhagia, patient satisfaction, mean volume of
      myoma, and hemoglobin level at 1, 3, 6, and 12 months after the procedure.
      RESULTS: The mean age of the patients was 38.7 years (range 26-49). The mean
      operating time was 17 minutes (range 11-44). The mean postoperative time to
      discharge home was 2.3 hours (range 1.6-3.2). There were 2 (1.46%) patients with
      type III-b complications (Clavien-Dindo classification). The mean (standard
      deviation [SD]) preoperative myoma volume was 122.4 [182.5] cm3. There was a
      significant reduction in the mean volume at 1 (85.2 [147.9] cm3; P = .001), 3
      (67.3 [138.0] cm3; P = .001), 6 (59.3 [135.3] cm3; P = .001), and 12 months (49.6
      [121.4] cm3; P = .001). The mean volume reduction at 12 months was 60% when
      compared with preoperative volume. All patients had normal menstruation at a mean
      follow-up of 3 months (range 1.5-6). CONCLUSION: TRFAM is an effective and safe
      technique in selected patients for the treatment of metrorrhagia secondary to
      myomas.

PMID- 30198832
TI  - Infections and stroke: Which potential pathogenic mechanism?

PMID- 30198833
TI  - Effect of the wetland environment on particulate matter and dry deposition.
AB  - In Beijing, particulate matter (PM) in the atmosphere, especially PM2.5 and PM10,
      have attracted public attention because of its adverse effects. A series of
      studies have investigated the sources and spatial-temporal variation of PM.
      Wetland has been reported to own the capacity of resolving air problem. To
      examine the characteristics of the particulate matter in wetlands, the diurnal
      variation of PM2.5 and PM10 concentrations with respect to two heights (i.e. 1.5
      and 10 m, respectively) and three meteorological factors (i.e. wind speed,
      temperature, and relative humidity, respectively) was monitored in the Cuihu
      National Wetland Park in Beijing, and the dry deposition velocity and flux were
      analysed using the above-mentioned data. Results indicated that (1) As for
      diurnal variation, the PM concentration constantly decreased at 07:00-16:00 and
      gradually increased at 16:00-18:00. The maximum instantaneous concentration was
      observed at 07:00-10:00, while the minimum instantaneous concentration was
      observed at 13:00-16:00. (2) The annual concentration variation of PM followed
      the order of dry period > wet period > normal period. (3) The particulate
      concentrations at 10 m were always greater than those at 1.5 m. (4) The PM
      concentration was positively correlated to the relative humidity and negatively
      correlated to the temperature. Wind speed exhibited a complex effect on PM
      concentration. (5) The regulation of dry deposition efficiency followed the order
      of spring > winter > summer. (6) Wind speed strongly and positively affected the
      dry deposition velocity of PM10. The effects of temperature and relative humidity
      on dry deposition were uncertain.

PMID- 30198834
TI  - Comparison of urine and serum neutrophil gelatinase-associated lipocalin after
      open and endovascular thoraco-abdominal aortic surgery and their meaning as
      indicators of acute kidney injury.
AB  - BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) has been described
      as a potential biomarker of acute kidney injury (AKI) in different settings, but
      its behaviour under influence of open and endovascular repair of thoraco
      abdominal aortic aneurysms (TAAA) has not been assessed yet. In this study, the
      course of NGAL was observed and differences of serum- (sNGAL) and urine-NGAL
      (uNGAL) levels following TAAA repair, especially with regard to AKI, were
      evaluated. PATIENTS AND METHODS: In this retrospective single centre study, 52
      patients (mean age 64.5 years, [43-85 years]), including 39 (75 %) men, were
      enrolled (2014-2015, 13.2 months mean follow-up). Levels of sNGAL and uNGAL were
      measured perioperatively for 48 hours on intensive care unit. Twenty-three
      patients were treated by endovascular and 29 by open TAAA-repair. RESULTS:
      Logistic regression revealed an increase in NGAL (sNGAL p = 0.0263, uNGAL p =
      0.0080) corresponding with an increase in serum creatinine within the first 48
      hours. Fourteen patients (26.9 %) developed AKI and 11 (21.1 %) required
      dialysis. The course of NGAL differed significantly (uNGAL p < .0001, sNGAL p =
      0.0002) between patients suffering from AKI requiring dialysis and patients
      without AKI. The predictive power of uNGAL was three times higher than that of
      sNGAL (estimate of the regression slope 0.1382 vs. 0.0460). No significant
      difference between patients undergoing open or endovascular TAAA repair regarding
      the perioperative course of sNGAL and uNGAL was observed. CONCLUSION: serum-NGAL
      and urine-NGAL correlate with serum creatinine levels and AKI requiring dialysis.
      Furthermore, the postoperative course of sNGAL and uNGAL after open and
      endovascular TAAA repair is not significantly different. Taken together, the
      results indicate that uNGAL and, to a lesser extent, sNGAL could be considered
      biomarkers for early detection of perioperative AKI after open and endovascular
      TAAA surgery.

PMID- 30198835
TI  - Phytoremediation of waste dumping site soil and landfill leachate by using
      cattail (Typha latifolia).
AB  - In this study, cattail (Typha latifolia) was used to remove Na+ and Cl- from
      polluted soil (PS) in a solid waste open dumping site. Hydroponic system was also
      evaluated to remove Na+ and Cl- from landfill leachate. The results indicated
      that the cattail grown in PS had higher biomass yield of 44.4 +/- 3.29 g compared
      to that of control (35.3 +/- 4.28 g). Nitrogen and phosphorous contents of
      cattails grown in PS were also higher than that of control plants, and the
      electrical conductivity of PS significantly decreased from 245 +/- 1.40 to 51.9
      +/- 9.30 ms/m over the 5-week experimental duration. Na+ and Cl- contents from
      cattail grown on PS were 10.8 +/- 1.85 and 64.7 +/- 9.15 g/kg biomass,
      respectively. For cattails grown hydroponically in water containing leachate,
      nitrogen and phosphorous accumulation was 51.1 +/- 5.94 and 9.32 +/- 3.22 g/kg
      biomass, respectively. The corresponding biomass yield of these cattails was 13.5
      +/- 1.29 g at the end of 5 weeks. In addition, the Na+ and Cl- accumulation of
      55.5 +/- 4.82 and 78.2 +/- 28.3 g/Kg biomass, respectively, was higher in
      hydroponic cattails grown in this study. Overall, the results suggest the
      effectiveness of cattails for phytoremediation of contaminated soil and the high
      efficiency of hydroponic system for nutrient and salinity removal compared to the
      conventional soil test.

PMID- 30198837
TI  - Is it time to reconsider epidemiological treatment for gonorrhoea?

PMID- 30198836
TI  - Exploring and integrating discrete and dimensional approaches while inducing
      negative emotional states.
AB  - Selecting visual stimuli for inducing specific emotional states is very
      challenging, since the choice relies on specific conceptualization of emotions.
      In this work, we present a set of 55 stimuli, realized integrating discrete and
      dimensional theories of emotions, and specifically selected to investigate anger,
      fear, and disgust reactions in non-clinical and clinical contexts. Our set of
      stimuli presents several aspects of novelty since (1) a large and heterogeneous
      sample of subjects from the general population was involved in the labelling
      task, and (2) bivariate and multivariate statistical techniques were applied to
      integrate emotion models. The proposed set of stimuli could be useful for
      researchers and other professionals in the affective sciences to address negative
      emotion recognition issues within a broader perspective both in general
      population and in psychiatric samples. The obtained comprehensive
      characterization of the stimuli allowed us to confirm the sexual dimorphism in
      emotional processing.

PMID- 30198838
TI  - Dolichoectasia Presenting as Renal Artery Aneurysm in a Deceased Donor Kidney: A
      Case Report and Review of the Literature.
AB  - We describe a case of fusiform aneurysm of the renal artery on a background of
      dolichoectasia in a kidney recovered from a deceased donor. The donor, a 57-year
      old female, had died of an extensive nonsurvivable subarachnoid hemorrhage.
      Fusiform aneurysms involving the main renal artery and its superior branch had
      extended into the hilum with insufficient accessible stump for safe
      reconstruction. Placement of a stent through an intraoperative radiologic
      intervention was not possible without compromising renal perfusion. Consequently,
      renal transplant did not proceed. Dolichoectasia is a condition associated with
      generalized weakness of the arterial vascular wall and may result in aneurysm
      formation. When the renal artery is involved, a safe reconstruction excising the
      aneurysmal segment may be considered before transplant of the kidney.

PMID- 30198839
TI  - Otorhinolaryngologic Problems in Liver and Kidney Transplant Recipients.
AB  - OBJECTIVES: The aim of this study was to define the otorhinolaryngologic
      manifestations and clinical characteristics of patients who received kidney or
      liver transplants at a university hospital. MATERIALS AND METHODS: Medical
      records of patients who received a kidney or liver transplant between 2000 and
      2013 and who were referred or applied to the ear, nose, and throat clinic were
      retrospectively reviewed. Otorhinolaryngologic complaints, signs, examination
      findings, and diagnoses of patients were noted. RESULTS: Our analyses included
      540 visits to the ear, nose, and throat clinic by 101 liver and 191 kidney
      transplant recipients. Mean duration between date of transplant and
      otorhinolaryngologic examination was 747.9 +/- 37.1 days. The most common
      complaint was rhinorrhea (n = 112), whereas the most common diagnosis was acute
      rhinosinusitis (n = 85). Acute upper respiratory tract infections, including
      rhinosinusitis, were diagnosed more frequently during the late postoperative
      period (ie, > 180 days after transplant). Epistaxis was more frequent during the
      first 30 days after transplant. CONCLUSIONS: A diverse variety of
      otorhinolaryngologic conditions, including emergencies and potentially life
      threatening infections, were seen in our kidney and liver transplant recipients,
      both during the early and the late follow-up period. All transplant team members
      should be familiar with the clinical presentation of frequently seen
      otorhinolaryngologic diseases.

PMID- 30198840
TI  - Pilot Conversion Study From Mycophenolate Mofetil to Everolimus in Stable ABO
      Incompatible Kidney Transplant Recipients: Analysis of 1-Year Follow-Up Data.
AB  - OBJECTIVES: Here, we report our 1-year follow-up data of stable ABO-incompatible
      kidney transplant recipients who converted from mycophenolate mofetil plus a
      standard dose of a calcineurin inhibitor to everolimus plus low exposure to
      calcineurin inhibitors. MATERIALS AND METHODS: Our study included 17 recipients
      of ABO-incompatible kidney transplant procedures performed at our institution. At
      baseline and at 3 and 12 months after conversion, graft biopsies were performed
      to check for acute rejection and C4d deposition. RESULTS: Treatment with
      everolimus was stopped due to adverse events in 8 patients (47.1%). Conversion to
      everolimus with calcineurin inhibitor minimization did not induce acute rejection
      or C4d deposition at 3 and 12 months after conversion in ABO-incompatible kidney
      transplant recipients in whom everolimus was maintained or stopped within 1 year
      after conversion. CONCLUSIONS: Everolimus elicited no acute rejection and no C4d
      deposition, whether everolimus was maintained or stopped within 1 year after
      conversion, in ABO-incompatible kidney transplant recipients.

PMID- 30198841
TI  - Peptidoglycan precursor synthesis along the sidewall of pole-growing
      mycobacteria.
AB  - Rod-shaped mycobacteria expand from their poles, yet d-amino acid probes label
      cell wall peptidoglycan in this genus at both the poles and sidewall. We sought
      to clarify the metabolic fates of these probes. Monopeptide incorporation was
      decreased by antibiotics that block peptidoglycan synthesis or l,d
      transpeptidation and in an l,d-transpeptidase mutant. Dipeptides complemented
      defects in d-alanine synthesis or ligation and were present in lipid-linked
      peptidoglycan precursors. Characterizing probe uptake pathways allowed us to
      localize peptidoglycan metabolism with precision: monopeptide-marked l,d
      transpeptidase remodeling and dipeptide-marked synthesis were coincident with
      mycomembrane metabolism at the poles, septum and sidewall. Fluorescent pencillin
      marked d,d-transpeptidation around the cell perimeter further suggested that the
      mycobacterial sidewall is a site of cell wall assembly. While polar peptidoglycan
      synthesis was associated with cell elongation, sidewall synthesis responded to
      cell wall damage. Peptidoglycan editing along the sidewall may support cell wall
      robustness in pole-growing mycobacteria.

PMID- 30198842
TI  - Decoupled maternal and zygotic genetic effects shape the evolution of
      development.
AB  - Evolutionary transitions from indirect to direct development involve changes in
      both maternal and zygotic genetic factors, with distinctive population-genetic
      implications, but empirical data on the genetics of such transitions are lacking.
      The polychaete Streblospio benedicti provides an opportunity to dissect a major
      transition in developmental mode using forward genetics. Females in this species
      produce either small eggs that develop into planktonic larvae or large eggs that
      develop into benthic juveniles. We identify large-effect loci that act maternally
      to influence larval size and independent, unlinked large-effect loci that act
      zygotically to affect discrete aspects of larval morphology. The likely fitness
      of zygotic alleles depends on their maternal background, creating a positive
      frequency-dependence that may homogenize local populations. Developmental and
      population genetics interact to shape larval evolution.

PMID- 30198846
TI  - Metadata Correction: Alcohol Consumption Reduction Among a Web-Based Supportive
      Community Using the Hello Sunday Morning Blog Platform: Observational Study.
AB  - [This corrects the article DOI: 10.2196/jmir.9605.].

PMID- 30198843
TI  - Intrinsic cooperativity potentiates parallel cis-regulatory evolution.
AB  - Convergent evolutionary events in independent lineages provide an opportunity to
      understand why evolution favors certain outcomes over others. We studied such a
      case where a large set of genes-those coding for the ribosomal proteins-gained
      cis-regulatory sequences for a particular transcription regulator (Mcm1) in
      independent fungal lineages. We present evidence that these gains occurred
      because Mcm1 shares a mechanism of transcriptional activation with an ancestral
      regulator of the ribosomal protein genes, Rap1. Specifically, we show that Mcm1
      and Rap1 have the inherent ability to cooperatively activate transcription
      through contacts with the general transcription factor TFIID. Because the two
      regulatory proteins share a common interaction partner, the presence of one
      ancestral cis-regulatory sequence can 'channel' random mutations into functional
      sites for the second regulator. At a genomic scale, this type of intrinsic
      cooperativity can account for a pattern of parallel evolution involving the
      fixation of hundreds of substitutions.

PMID- 30198847
TI  - [Altered urinary calcium excretion in prostate cancer patients subjected to
      androgen deprivation. Preliminary pilot study results.]
AB  - OBJECTIVES: Androgen deprivation therapy (ADT) in prostate cancer is associated
      with the appearance of different adverse effects. Among these effects, notable
      ones that may affect metabolism are osteoporosis and metabolic syndrome. The aim
      of this study is to analyse lithogenic risk markers three months after initiating
      treatment with LHRH analogue. METHODS: Pilot study encompassing 15 prostate
      cancer patients who were candidates for ADT, which they received in the form of
      quarterly doses of goserelin 10.8 mg. A blood and urine analyses for lithogenic
      risk, bone and metabolic markers were carried out, as was a study of metabolic
      syndrome criteria. Statistical analysis was performed with SPSS 17.0, taking
      P<=.05 to be statistically significant. RESULTS: Patients included in the study
      had a mean age of 72.46 +/- 6.61 years. We observed a significant increase in the
      percentage of metabolic syndrome (20% versus 46.7%; P<.05) and insulin resistance
      index (1.87 versus 2.96; P=.01) at 3 months treatment. There was a notable
      increase in bone remodelling markers and significant increases in 24 h urinary
      calcium values (9.46 versus 14.57 mg/dl; P=.008), 24 h urinary calcium excretion
      index (0.10 versus 0.13 mg/dl GF [glomerular filtration]; P=.01) and the fasting
      calcium/ creatinine ratio (0.107 versus 0.195; P=.007), without any changes to
      other lithogenous risk markers. CONCLUSIONS: Androgen deprivation therapy can
      lead to the short-term appearance, primarily when fasting, of hypercalciuria in
      prostate cancer patients, possibly in association with bone metabolism.

PMID- 30198849
TI  - [Evanescent carcinoma of the prostate. Incidence, clinical and histopathological
      characteristics.]
AB  - OBJECTIVE: To determine the incidence and clinical and histopathological
      characteristics of patients with prostatic evanescent carcinoma in the Urology
      Department of the Hospital Universitario de Caracas. METHODS: We reviewed the
      medical records of 257 patients undergoing radical prostatectomy for a previous
      diagnosis of prostatic carcinoma in the period January 2010 to June 2016.
      RESULTS: Four patients had evanescent carcinoma corresponding to 1.55%, similar
      to documented studies, thus maintaining their percentage of appearance in time.
      Adenocarcinomas are usually associated with Gleason scores <=6, but they can
      present in carcinomas with less differentiated histopathological pattern, like
      Gleason 7 (3 + 4). CONCLUSIONS: In the pathological study of the specimen of
      radical prostatectomy of patients with evanescent carcinoma, it is advisable to
      apply additional immunohistochemistry technique or seek for a second pathological
      opinion, to confirm this entity, and to rule out a technical or interpretation
      failure.

PMID- 30198848
TI  - [Relationship between anogenital distance and prognosis of prostate cancer.]
AB  - OBJECTIVE: Anogenital distance (AGD), the distance from the centre of the anus to
      the genitals, is a sexually dimorphic phenotype in mammals. Several experimental
      studies have demonstrated that AGD is a biomarker of prenatal androgen exposure
      during the masculinisation period of development. The objective of this study was
      to assess the relationship between AGD (as an indirect marker of prenatal
      hormonal environment) and severity of the surgical specimen and prostate cancer
      (PCa) prognosis. METHODS: We conducted a cross-sectional study with a total of
      119 PCa patients with confirmed biopsy of the tumour. Every participant underwent
      a physical examination where two variants of the AGD were assessed, a) from the
      anus to the cephalad insertion of the penis (AGDAP) and b) to the posterior base
      of the scrotum (AGDAS). To assess the association between both AGD and severity
      and PCa prognosis multiple logistic regression analysis was used. RESULTS: Longer
      AGDAS was significantly associated with biochemical recurrence and affected
      margins of the surgical specimen (OR: 2.5; IC 95%:1.2-5.5, and 2.8; IC 95%: 1.1
      7.5, respectively). CONCLUSIONS: Our findings suggest that a higher prenatal
      androgen exposure, resulting in a longer AGD, is associated with worse prognosis
      of PCa.

PMID- 30198850
TI  - [Radical post-prostatectomy biochemical relapse in patients with pathological
      factors treated with adjuvant versus observation radiotherapy in Colombia.]
AB  - OBJECTIVE: In patients with prostate cancer and high-risk pathological factors,
      adjuvant radiotherapy (ART) has been reported to be superior to observation for
      local disease control and progressionfree survival. But more than 30% of the
      patients do not present biochemical relapse (BR) and therefore the ART associated
      with the toxicity can be avoided. It has not been determined whether close
      observation with early salvage radiotherapy provides a similar result to ART.
      METHODS: Patients with localized prostate cancer treated with radical
      prostatectomy (RP) at the Institute of Cancerology (Medellin-Colombia), and those
      who had adverse predictors of biochemical relapse were included: extracapsular
      compromise, seminal vesicle involvement (pT3), and positive surgical margins
      (PSM) or not. Biochemical progression-free survival was compared between ART
      group and the observation group. RESULTS: Of 171 patients treated with RP, 55 had
      at least one adverse pathological factor. Of them, 33 (60%) were observed and 22
      (40%) received ART. The median follow-up was 55 months (IQR: 37-89). Biochemical
      relapse occurred in 6 (18.2%) of the first group and 3 (13.6%) of the second
      group (p>0.05). Biochemical progression-free survival was 24.2% (95%CI: 11.5%
      39.6%) in the observation group and 47.7% (95CI: 26.3%-66.4%) in the ART.
      CONCLUSIONS: After radical prostatectomy, the biochemical relapse in the patient
      with high-risk prostate cancer was similar in the observation group and in the
      ART group.

PMID- 30198845
TI  - Allosteric regulators selectively prevent Ca2+-feedback of CaV and NaV channels.
AB  - Calmodulin (CaM) serves as a pervasive regulatory subunit of CaV1, CaV2, and NaV1
      channels, exploiting a functionally conserved carboxy-tail element to afford
      dynamic Ca2+-feedback of cellular excitability in neurons and cardiomyocytes. Yet
      this modularity counters functional adaptability, as global changes in ambient
      CaM indiscriminately alter its targets. Here, we demonstrate that two
      structurally unrelated proteins, SH3 and cysteine-rich domain (stac) and
      fibroblast growth factor homologous factors (fhf) selectively diminish Ca2+/CaM
      regulation of CaV1 and NaV1 families, respectively. The two proteins operate on
      allosteric sites within upstream portions of respective channel carboxy-tails,
      distinct from the CaM-binding interface. Generalizing this mechanism, insertion
      of a short RxxK binding motif into CaV1.3 carboxy-tail confers synthetic
      switching of CaM regulation by Mona SH3 domain. Overall, our findings identify a
      general class of auxiliary proteins that modify Ca2+/CaM signaling to individual
      targets allowing spatial and temporal orchestration of feedback, and outline
      strategies for engineering Ca2+/CaM signaling to individual targets.

PMID- 30198844
TI  - Glutathione de novo synthesis but not recycling process coordinates with
      glutamine catabolism to control redox homeostasis and directs murine T cell
      differentiation.
AB  - Upon antigen stimulation, T lymphocytes undergo dramatic changes in metabolism to
      fulfill the bioenergetic, biosynthetic and redox demands of proliferation and
      differentiation. Glutathione (GSH) plays an essential role in controlling redox
      balance and cell fate. While GSH can be recycled from Glutathione disulfide
      (GSSG), the inhibition of this recycling pathway does not impact GSH content and
      murine T cell fate. By contrast, the inhibition of the de novo synthesis of GSH,
      by deleting either the catalytic (Gclc) or the modifier (Gclm) subunit of
      glutamate-cysteine ligase (Gcl), dampens intracellular GSH, increases ROS, and
      impact T cell differentiation. Moreover, the inhibition of GSH de novo synthesis
      dampened the pathological progression of experimental autoimmune
      encephalomyelitis (EAE). We further reveal that glutamine provides essential
      precursors for GSH biosynthesis. Our findings suggest that glutamine catabolism
      fuels de novo synthesis of GSH and directs the lineage choice in T cells.

PMID- 30198851
TI  - [Cost-effectiveness model of a fixed dose combination of solifenacin and
      tamsulosin for the treatment of LUTS associated with BPH with inadequate response
      to monotherapy.]
AB  - OBJECTIVE: To compare the cost-effectiveness of fixed dose combination of
      solifenacin 6 mg and tamsulosin 0.4 mg in a controlled absorption system (TOCAS)
      with free dose combination of tolterodine plus tamsulosin, when used for the
      treatment of patients with moderate to severe lower urinary tract symptoms (LUTS)
      associated with benign prostatic hyperplasia (BPH) who do not respond adequately
      to monotherapy. The analysis was conducted from the perspective of the Spanish
      National Health System. METHODS: A Markov model was developed in Excel, with 1
      year time horizon. The transition probabilities of the model were obtained from
      the NEPTUNE clinical trial and published literature. Unit costs were obtained
      from Spanish sources. The use of healthcare resources was validated by Spanish
      clinical experts. Both deterministic and probabilistic analyses were performed to
      determine the key drivers of the model. RESULTS: Treatment with fixed dose
      combination of solifenacin plus TOCAS was found to be dominant, as it resulted in
      lower annual costs (? 1,349 vs. ? 1,619) and greater quality-adjusted life years
      (QALY) gained per patient (0.8406 vs. 0.8386) when compared with free dose
      combination of tolterodine plus tamsulosin. According to the probabilistic
      analyses, the probability of the fixed dose combination treatment being cost
      effective at a willingness to pay threshold of ? 20,000 or 30,000 would be 100%.
      CONCLUSIONS: This analysis suggests that fixed dose combination of solifenacin
      plus TOCAS represents a cost-effective choice for the treatment of patients with
      moderate to severe LUTS/BHP, compared to free dose combination of tolterodine
      plus tamsulosin.

PMID- 30198852
TI  - Antireflux ureteral stent proof of concept assessment after minimally invasive
      treatment of obstructive uropathy in animal model.
AB  - OBJECTIVES: To assess the efficacy of a new anti-reflux intraureteral stent
      design in a swine model after minimally invasive treatment of ureteral stricture
      to reduce ureteral stent morbidity, previous to manufacture this design in a
      biodegradable fashion. METHODS: Twenty-eight female pigs were included. The study
      began with a cystoscopic, nephrosonographic and contrast fluoroscopic assessment.
      Afterwards, obstructive uropathy model in right ureter was created. Obstruction
      was confirmed 6 weeks later and animals were randomly distributed into 2 groups.
      Group I underwent laser endopyelotomy and Group-II laparoscopic pyeloplasty A 3Fr
      anti-reflux intraureteral stent was placed 6 weeks. Follow-up evaluations were
      performed at 3-6 weeks. The final follow-up was completed at 5 months and
      included the aforementioned diagnostic methods and pathological study. RESULTS:
      None of the study animals showed any vesicoureteral reflux signs or ureteral
      orifice injury. There were no urinomas or ureteric fistulas. The dislodgement
      rate was 10.7%. After 6 weeks of stenting, 71.4% of ureters showed ureteral
      peristalsis below the stent, and 100% at the final follow-up. After pathological
      assessment, no differences were shown at UPJ and healing in the incised area was
      correct in both groups. CONCLUSIONS: The new stent design avoids vesicoureteral
      reflux and bladder trigone irritation, consequently might reduce morbidity
      associated with double pigtail ureteral stents. This study also shows that it is
      only necessary temporary scaffolding the incised ureteral segment and not the
      entire length of the ureter after minimally invasive surgery. It is also
      necessary to manufacture this design in a biodegradable material, thus avoiding
      its removal.

PMID- 30198853
TI  - [Prostate carcinosarcoma.]
AB  - OBJECTIVE: To report a new case of prostatic carcinosarcoma, an uncommon and
      locally and distance aggressive tumor. METHOD: We analyzed one case diagnosed in
      our Center, from clinical and pathological diagnosis to death, describing the
      treatments received. RESULT: Patient presented a huge pelvic mass and a pulmonary
      metastasis that was treated with cystoprostatectomy and bilateral cutaneous
      ureterostomy with the diagnosis of carcinosarcoma of the prostate. He received 8
      cycles of Docetaxel with bone progression and then 3 cycles of doxorubicin,
      suspending treatment due to progression. The survival was 18 months. CONCLUSIONS:
      Prostate carcinosarcoma is a very aggressive neoplasia that does not respond to
      the usual treatments of prostate cancer.

PMID- 30198854
TI  - Purple urine bag syndrome, a travel companion.
AB  - OBJECTIVE: Purple urine bag syndrome is a rare entity that appears in elderly
      patients with long-term urinary catheters with chronic diseases. METHOD: We
      describe the cases of two patients admitted to our service, who serve as example
      to illustrate this pathology and which process should be followed in its
      diagnosis and treatment. CONCLUSION: Purple urine bag syndrome is a rare entity
      that occurs more frequently in elderly patients, women, with long-term urinary
      catheters, whose main factors are debilitating diseases, prolonged immobility and
      chronic constipation. It should be treated by avoiding the triggering factors,
      adequate hydration of the patient, antibiotics directly antibiogram therapy and
      the change of urinary catheter can be evaluated.

PMID- 30198855
TI  - Large size stone impacted in urethral meatus.

PMID- 30198856
TI  - Sports renal injury: Emergency nephrectomy.

PMID- 30198857
TI  - Squeezing and time evolution of magnon states under perpendicular pumping.
AB  - The coherent magnon state representation is employed to investigate the quantum
      statistical behavior of the nonlinear excitation of magnons in ferromagnets. Both
      the long-range magnetic dipole-dipole and short-range exchange interactions are
      included, along with a static longitudinal applied field and a microwave pumping
      field in the perpendicular orientation. Within a microscopic (or Hamiltonian
      based) approach the total Hamiltonian is transformed from spin operators to a
      normal-mode set of boson creation and annihilation operators. When the three
      magnon interactions are included, it is found that the microwave pumping field
      may be used to control the nonlinear statistical properties of the system. From a
      study of the time evolution of the system we deduce the average number of
      magnons, the super-Poissonian statistical behavior, and the occurrence of magnon
      squeezing. We also compare the results with the case where the microwave pumping
      field is in the parallel orientation, and it is found that there are important
      differences in the time dependence.

PMID- 30198858
TI  - Ionic liquids-a novel material for planar photonics.
AB  - Electron beam patterning is an important technology in the fabrication of
      miniaturized photonic devices. The fabrication process conventionally involves
      the use of radiation sensitive polymer-based solutions (called resists). We
      propose to replace typical polymer resists with eco-friendly solvent-free room
      temperature ionic liquids (RTILs), which are polymerized in situ and solidified
      by an electron beam. It is demonstrated that the shapes of polymerized structures
      are different for high-viscous Cl-based RTILs and low-viscous NTf2-based RTILs.
      Due to the the satisfactory quality of the polymerized spatial microstructures
      and their light transmission properties, the RTIL-derived microstructures are
      potentially attractive as photonic elements for near-infrared.

PMID- 30198859
TI  - Synthesis of OSL nanophosphor Li3B7O12:Mn and its dosimetric properties.
AB  - The present paper reports the structural, morphological and optical properties of
      nanophosphor Li3B7O12:Mn with an optimised dopant concentration of 0.25 mol% and
      its surface modification under the irradiation of 250 keV proton beams and gamma
      photons for ion fluence ranging from 1 * 1013 to 6.25 * 1015 ions cm-2 and doses
      from 100 mGy-100 Gy, respectively. This nanophosphor has been synthesised by the
      high temperature solid state reaction method. Its optical properties are
      characterised by optically stimulated luminescence (OSL) and thermo luminescence
      (TL) techniques. This nanophosphor is polycrystalline in nature with a grain size
      of 40-80 nm confirmed by x-ray diffraction (XRD) and transmission electron
      microscopy (TEM). The OSL decay and TL glow curve response of the proton beam
      irradiated samples exhibit significant intensity at a fluence of 2.5 * 1014 ions
      cm-2. Moreover, Li3B7O12:Mn displays a linear response for gamma doses in the
      range of 100 mGy-50 Gy. We have also investigated the reusability and
      reproducibility of this material. The above study demonstrates that Li3B7O12:Mn
      is a robust and promising candidate for medical proton dosimetry.

PMID- 30198860
TI  - Nanometrology of field gradient using donor spins in silicon.
AB  - We proposed a novel scheme for nanometrology of magnetic field gradient based on
      Kane's silicon quantum computer proposal. When the system is placed in an unknown
      magnetic field gradient, the inhomogeneous precession of the donor nuclear spins
      records the field gradient information to the phase pattern of donor nuclear
      spins. By adding AC voltage modulations on each A-gate to induce hyperfine
      mediated electron-nuclear collective flip-flop process, we demonstrate that the
      gradient value can be obtained by tuning the modulation phases of the A-gates.
      Errors of the measurements of such scheme is discussed and estimated. It is also
      discussed that in presence of the external field with a known gradient, the same
      system is possible to be used to obtain the unknown displacement of donor
      locations.

PMID- 30198861
TI  - Re-excision rate after sector resection for breast cancer: A 5-year retrospective
      cohort study.
AB  - BACKGROUND: Positive margins after Breast conserving surgery (BCS) for breast
      cancer can result in local recurrence (LR) requiring further surgery. This can
      lead to unnecessary patient anxiety, poor prognosis and impose additional
      economic burden to our health system. The aim of this study is to assess the rate
      of re-excision for positive margins after BCS using the sector resection
      technique. METHODS: This single centre retrospective cohort study included all
      women who underwent BCS using sector resection between the years of 2012 and
      2016. A total of 456 patients underwent sector resection. We evaluated the margin
      status, re-excision rates and their predictive risk factors. RESULTS: 415 (91%)
      patients had clear margins. 41 (9%) patients underwent further re-excision for
      positive or close margin. 75.6% of those patients had DCIS and 51% had invasive
      carcinoma involving the margins. Patient and tumour characteristics associated
      with an increased risk of positive margin were women under the age of 50 (p =
      0.19), tumours >50 mm (p = 0.001), grade-2 (p = 0.48) and grade-3 (p = 0.63), HER
      2 positivity (p = 0.02), sentinel lymph node positivity (p = 0.03), and patients
      undergoing axillary lymph node dissection (p = 0.01). CONCLUSION: BCS using the
      sector resection technique has a low re-excision rate for positive margins.
      Younger patients and aggressive tumour biology are important predictive risk
      factors for positive margins.

PMID- 30198862
TI  - Clinical risk analysis of non-visualized sentinel lymph node in breast cancer.
AB  - OBJECTIVE: This study aimed to explore the positive rate of non-visualized
      sentinel lymph nodes (non-vSLN) [1] in breast cancer (BC) patients and the
      discrepancy of non-vSLN among different molecular subtypes, in order to further
      evaluate the clinical risk of non-vSLNs. METHODS: A total of 627 patients were
      retrospectively analyzed. These patients were pathologically confirmed with
      invasive breast cancer and underwent sentinel lymph node biopsy (SLNB). Various
      factors were compared using chi-square test. The positive rate of SLNs between
      non-vSLNs and visible sentinel lymph nodes (vSLNs) were compared. Moreover,
      factors that influenced the prognosis, such as ER, PR, HER-2, histological grade
      and lymph node metastasis were compared between these two groups. RESULTS: Among
      the 627 patients who underwent SLNB, 196 patients had non-vSLNs, accounting for
      31.26% (196/627) and 113 patients had positive SLNs, accounting for 18.02%
      (113/627). Furthermore, 40.71% (46/113) of patients with positive SLNs had non
      vSLN, and 17.39% (8/46) of patients with non-vSLN had HER-2+BC. In contrast,
      35.82% (24/67) of patients with vSLNs had HER-2+BC. Moreover, 23.91% (11/46) of
      patients with non-vSLN and 5.97% (4/67) of patients with vSLNs had triple
      negative breast cancer (TNBC). The metastasis rate was 41.30% (19/46) in the non
      vSLN group and 43.28% (29/67) in the vSLN group. The difference in the rate of
      positive SLNs between the non-vSLN and the vSLN groups was statistically
      significant (P< 0.05), in which the positive rate of SLNs in the non-vSLN group
      was remarkably higher than that in the vSLN group. The differences in the
      proportion of HER-2+BC and TNBC between the non-vSLN and the vSLN groups were
      statistically significant (P< 0.05), in which HER-2+BCwas evidently higher in the
      vSLN group than in the non-vSLN group. Meanwhile, TNBC was markedly higher in non
      vSLN group than in the vSLN group. Furthermore, differences in Luminal A subtype,
      Luminal B subtype and non-SLN metastasis between these two groups was not
      statistically significant. In addition, the difference in non-SLN metastasis rate
      was not statistically significant among breast cancers of different molecular
      subtypes and between the non-vSLN and the vSLN groups. CONCLUSION: Breast cancer
      patients with positive non-vSLNs are more likely to have a TNBC subtype relative
      to patients with positive vSLN. Breast cancer patients with non-vSLN have higher
      positive rate of SLNs. The non-SLN metastasis rate in positive SLN patients was
      not correlated to the molecular subtype of breast cancer.

PMID- 30198863
TI  - Five serum-based miRNAs were identified as potential diagnostic biomarkers in
      gastric cardia adenocarcinoma.
AB  - BACKGROUND: Circulating microRNAs (miRNAs) have been implicated as novel
      biomarkers for various types of cancers. The aim of the study is to identify
      serum miRNAs with potential in detecting gastric cardia adenocarcinoma (GCA).
      METHODS: A three-phase study was designed with 102 GCA patients and 84 cancer
      free controls. In the screening phase (3 GCA pools vs. 1 normal control (NC)
      pool), a total of 35 miRNAs were identified using quantitative reverse
      transcription polymerase chain reaction (qRT-PCR) based Exiqon panel.
      Subsequently, these miRNAs were further assessed by qRT-PCR in the training phase
      (30 GCAs vs. 30 NCs) and testing phase (72 GCAs vs. 54 NCs). Finally, the
      expression levels of the identified miRNAs were assessed in GCA tissues and
      exosomes. RESULTS: Five up-regulated miRNAs (miR-200a-3p, miR-296-5p, miR-132-3p,
      miR-485-3p and miR-22-5p) were identified in serum of the GCA patients compared
      with NCs. The areas under the receiver operating characteristic curve (AUCs) of
      the five-miRNA panel were 0.766 and 0.724 for the training and testing phases,
      respectively. In addition, miR-200a-3p, miR-296-5p, miR-485-3p and miR-22-5p were
      significantly up-regulated in GCA tissues. However, none of the miRNAs in the
      exosomes showed different expression between GCA patients and NCs. CONCLUSIONS:
      We identified a five-miRNA panel in peripheral serum samples as a non-invasive
      biomarker in detection of GCA.

PMID- 30198864
TI  - Preoperative platelet distribution width predicts breast cancer survival.
AB  - BACKGROUND: Breast cancer is one of the most commonly diagnosed cancers, and the
      fourth leading cause of cancer deaths in females worldwide. Activated platelets
      play a key role in tumor growth and tumor metastasis. Platelet distribution width
      (PDW) is a platelet index, and is altered in patients with malignancies. The aim
      of this study was to explore whether PDW can effectively predict death outcome of
      breast cancer patients. STUDY DESIGN: The clinical data of 271 breast cancer
      patients in our hospital between January 2009 and December 2009 were
      retrospectively analyzed. Survival analysis was performed using the log-rank test
      and Cox proportional hazards regression analysis. RESULT: There were significant
      correlations between increased PDW and tumor size, molecular subtype,
      differentiation grade, and cancer stages (T, N, or TNM). Moreover, survival
      analysis revealed that the overall survival of patients with PDW > 16.8%, which
      was significantly shorter than those with PDW ? 16.8%. Multivariate analysis
      indicated that PDW > 16.8% predicts a poor overall survival of breast cancer
      patients. CONCLUSIONS: Elevated PDW may serve as a marker of adverse prognosis in
      breast cancer. However, these data are preliminary and should be interpreted with
      caution pending validation by additional clinical and molecular/genomics studies
      in various populations.

PMID- 30198865
TI  - Recombinant adenovirus p53 combined with radiotherapy improves efficacy and
      safety in the treatment of head and neck lymphoma.
AB  - OBJECTIVE: Lymphoma is considered to be a kind of malignant tumour. Gene therapy
      and radiotherapy have been reported as treatment methods for head and neck
      lymphoma. This study aims to evaluate the efficacy and safety for the treatment
      of head and neck lymphoma by a combination of recombinant adenovirus p53 (rAd
      p53) and radiotherapy. METHODS: A total of 156 patients with head and neck
      lymphoma were selected. All patients received an intratumor injection of rAd-p53
      of four different doses, namely, 0, 1 * 1010 VP, 1 * 1011 VP and 1 * 1012 VP,
      once a week for 8 weeks, and radiotherapy was administered 3 days after the rAd
      p53 injection using the same dosage and method. Four, eight and twelve weeks
      after treatment, tumor reduction and complete response (CR) rates, special
      laboratory examination and adverse reaction assessment were detected to evaluate
      the efficacy and safety of combined treatment with rAd-p53 injection and
      radiotherapy for head and neck lymphoma. RESULTS: At week 4, 8 and 12 of
      treatment with rAd-p53 at the 1 * 1010 VP, 1 * 1011 VP and 1 * 1012 VP doses, the
      average tumour reduction and CR rates were evidently elevated, the anti rAd-p53
      antibody in the serum of patients was expressed positively, and the T cell
      subsets (CD3/CD4/CD8) increased and interleukin 2 receptor (IL-2R) level
      decreased markedly. Additionally, rAd-p53 was proven to be clinically safe in the
      treatment. CONCLUSION: Altogether, we conclude that rAd-p53 combined with
      radiotherapy improves the efficacy and safety in treating head and neck lymphoma,
      which has a broad scope in future clinical application.

PMID- 30198866
TI  - Differential expression of long non-coding RNA SOX2OT in gastric adenocarcinoma.
AB  - BACKGROUND: Gastric cancer (GC) is the third leading cause of cancer-related
      death in the world. Dysfunction of long noncoding RNAs (lncRNAs) in cancers,
      especially those with role in pluripotency, are approved by increasing evidence.
      OBJECTIVE: SOX2 overlapping transcript (SOX2OT) lncRNA, is aberrantly expressed
      in different cancers; however its role in gastric cancer is still controversial.
      MATERIALS AND METHODS: In this study, the expression of SOX2OT was evaluated in
      33 matched pair tumor and non-tumor gastric samples and AGS and MKN45 gastric and
      NTERA2 embryonic carcinoma cell lines by real time PCR. RESULTS: Our finding
      revealed a significant decrease in the expression of SOX2OT in gastric tumor
      samples compared to their matched non-tumor samples (P= 0.05) and also a lower
      expression in high grade compared to low grade of gastric malignancy. As we
      expected SOX2OT expression showed higher expression in NT2 compared to AGS and
      MKN45 cell lines. CONCLUSION: Simultaneous expression of SOX2 and SOX2OT was
      reported in some cancers. Regarding to the decreased expression of SOX2OT in the
      present study in concurrent with downregulation of SOX2 in our previous study, it
      seems that SOX2OT plays a tumor suppressor role in GC and may be useful biomarker
      for diagnosis of GC.

PMID- 30198867
TI  - Carbon nanoparticle lymph node tracer improves the outcomes of surgical treatment
      in papillary thyroid cancer.
AB  - BACKGROUND: Papillary thyroid carcinoma (PTC) is the most common thyroid
      malignancy which is generally accompanied by lymph node metastasis. OBJECTIVE:
      Our study evaluated whether carbon nanoparticle lymph node tracer can improve the
      outcomes of surgical treatment in papillary thyroid cancer (PTC). METHODS: Ninety
      two patients were selected and underwent total thyroidectomy and lymph node
      resection. Our study placed 45 individuals into the treatment group (carbon
      nanoparticle group) and 47 cohorts in the control group (no carbon nanoparticle
      group). RESULTS: Carbon nanoparticle application remarkably improved lymph nodes
      detection rate in patients (4.7 +/- 3.0; P< 0.05) compared to those in control
      groups (3.5 +/- 2.3). The rate of parathyroid accidental resection in the carbon
      nanoparticle group significantly decreased (6.67%) compared to the control group
      (21.28%). Incidents of hypoparathyroidism and hypocalcaemia significantly
      decreased among the carbon nanoparticle cohorts. CONCLUSIONS: Our study
      definitively showed that carbon nanoparticles can be used to effectively treat
      lymphatic carcinoma. Our study presented clinical evidences for potential
      application of carbon nanoparticle in improving the management of PTC patients.

PMID- 30198868
TI  - Down-regulation of long non-coding RNA ANRIL inhibits the proliferation,
      migration and invasion of cervical cancer cells.
AB  - OBJECTIVES: Cervical cancer (CC) is a common malignant tumor in the female
      reproductive system that is characterized by a high metastatic potential. LncRNA
      ANRIL has been found to be a cancer oncogene in multiple tumors. In our study, we
      altered the expression of ANRIL in CC cells and evaluated its ability on
      influencing proliferation, migration and invasion of CC cells and associated
      mechanism. METHODS: Differentially expressed lncRNAs in CC were identified by
      microarray and TCGA analyses. CC tissues and adjacent tissues were collected in
      order to extract CC cells. The expression of ANRIL was determined by RT-qPCR. The
      CC cells were transfected with siRNA or si-NC against ANRIL to find out whether
      ANRIL can influence the expression of Cyclin D1, CDK4, CDK6, E-cadherin, vimentin
      and N-cadherin, as well as affect cell proliferation, cell apoptosis, cell
      migration and cell invasion of CC cells. RESULTS: Based on TCGA and microarray
      analyses, ANRIL was predicted to be highly expressed in CC and CC with migration.
      Then further verification was obtained by means of RT-qPCR that ANRIL was highly
      expressed in CC tissues. In addition, high expression of ANRIL was related to
      increased E-cadherin expression, high migration of CC as well as decreased cell
      apoptosis rate. On the other hand, inhibition of ANRIL expression led to
      decreased expressions of Cyclin D1, CDK4, CDK6, N-cadherin and Vimentin, along
      with attenuated cell proliferation, migration and invasion of CC cells.
      CONCLUSION: The key findings of our study demonstrated that the inhibition of
      lncRNA ANRIL reduces the proliferation, migration and invasion capabilities of CC
      cells. Down-regulation of ANRIL may serve as a potential therapeutic target in
      the treatment of CC.

PMID- 30198869
TI  - Key miRNAs and target genes played roles in the development of clear cell renal
      cell carcinoma.
AB  - BACKGROUND: Clear cell renal cell carcinoma (CCRCC) is the most aggressive form
      of renal cell carcinoma (RCC). OBJECTIVE: This study was aimed to identify the
      differentially expressed miRNAs and target genes in CCRCC. METHODS: The miRNA and
      mRNA next-generation sequencing data were downloaded from The Cancer Genome Atlas
      (TCGA) dataset. Differential expression analysis was performed, followed by
      correlation analysis of miRNA-mRNA. Functional enrichment and survival analysis
      was also performed. RESULTS: Seven hundred and eighty-seven patients with CCRCC
      from TCGA data portal were included in this study. A total of 52 differentially
      expressed miRNAs were identified in CCRCC. Then 2361 differentially expressed
      genes (DEGs) were identified. Prediction analysis and correlation analysis
      revealed that 89 miRNA-mRNA pairs were not only predicted by algorithms but also
      had a significant inverse relationship. Several differentially expressed miRNAs
      such as hsa-mir-501 and their target genes including AK1, SLC25A15 and PCDHGC3
      had a significant prognostic value for CCRCC patients. CONCLUSIONS: Alterations
      of differentially expressed miRNAs and target genes may be involved in the
      development of CCRCC and can be considered as the prognostic markers for CCRCC.

PMID- 30198870
TI  - EIF3B correlates with advanced disease stages and poor prognosis, and it promotes
      proliferation and inhibits apoptosis in non-small cell lung cancer.
AB  - BACKGROUND: Although up-regulation of EIF3B correlates with poor prognosis in
      carcinomas, the role of EIF3B in non-small cell lung cancer (NSCLC) is rarely
      known. OBJECTIVE: We aimed to investigate correlation of EIF3B with
      clinicopathological features and prognosis in NSCLC patients, and clarify its
      effect on cells proliferation and apoptosis. METHODS: Two hundred and eleven
      NSCLC patients underwent surgery were retrospectively reviewed. Tumor tissue and
      paired adjacent tissue were obtained. EIF3B expression was detected by
      immunohistochemistry, qPCR and western blot. EIF3B inhibitor, blank inhibitor,
      blank mimic and EIF3B mimic plasmids were transfected to A-549 cells. Cells
      proliferation and apoptosis were measured by CCK-8 and AV/PI. All processes were
      repeated for validation in PC9 cells. RESULTS: EIF3B expression increased in
      tumor tissue compared to paired adjacent tissue, and positively correlated with
      tumor size, lymph node metastasis and TNM stage. K-M curves revealed patients
      with EIF3B high expression had shorter DFS and OS, and its high expression
      independently predicted unfavorable DFS and OS. In vitro, EIF3B expression
      increased in NSCLC cells compared to normal cells. EIF3B increased cells
      proliferation but inhibited cells apoptosis. CONCLUSIONS: EIF3B overexpression
      correlates with advanced disease conditions and poor prognosis, and it promotes
      cells proliferation while inhibits apoptosis in NSCLC.

PMID- 30198871
TI  - MiR-101 inhibits cell proliferation and invasion of pancreatic cancer through
      targeting STMN1.
AB  - MiRNAs regulated most genes expression, which were proved important in various
      tumors. In this study, we want to investigate miR-101 effect and molecular
      mechanism on pancreatic cancer (PC), the research about this was blank now. RT
      PCR analysis showed that miR-101 expression was declined in PC. MTT assay found
      that miR-101 mimic suppressed cell viability, while suppressing miR-101
      facilitated cell proliferation. Transwell assay showed that miR-101 mimic
      inhibited cell invasion, but promoted cell invasion by miR-101 inhibitor. With
      TargetScanHuman's help, we verified STMN1 as a specific target of miR-101 and
      luciferase reporter assay was carried out to further confirm this discovery.
      STMN1 expression was reduced by miR-101 mimic and increased by miR-101 inhibitor.
      We next found that STMN1 was elevated in PC and its expression was negatively
      correlated with miR-101 expression. Furthermore, STMN1 siRNA curbed cell
      proliferation and invasion, which was opposite to miR-101 inhibitor effect on PC
      progression and STMN1 siRNA attenuated miR-101 inhibitor effect on cell
      proliferation and invasion. In conclusion, miR-101 inhibited PC cell
      proliferation and invasion via regulating STMN1, which provided a potential
      therapeutic for PC patients.

PMID- 30198872
TI  - A Precision Medicine Model for Targeted NSAID Therapy in Alzheimer's Disease.
AB  - BACKGROUND: To date, the therapeutic paradigm for Alzheimer's disease (AD) has
      focused on a single intervention for all patients. However, a large literature in
      oncology supports the therapeutic benefits of a precision medicine approach to
      therapy. Here we test a precision-medicine approach to AD therapy. OBJECTIVE: To
      determine if a baseline, blood-based proteomic companion diagnostic predicts
      response to NSAID therapy. METHODS: Proteomic assays of plasma from a
      multicenter, randomized, double-blind, placebo-controlled, parallel group trial,
      with 1-year exposure to rofecoxib (25 mg once daily), naproxen (220 mg twice
      daily) or placebo. RESULTS: 474 participants with mild-to-moderate AD were
      screened with 351 enrolled into the trial. Using support vector machine (SVM)
      analyses, 89% of the subjects randomized to either NSAID treatment arms were
      correctly classified using a general NSAID companion diagnostic. Drug-specific
      companion diagnostics yielded 98% theragnostic accuracy in the rofecoxib arm and
      97% accuracy in the naproxen arm. CONCLUSION: Inflammatory-based companion
      diagnostics have significant potential to identify select patients with AD who
      have a high likelihood of responding to NSAID therapy. This work provides
      empirical support for a precision medicine model approach to treating AD.

PMID- 30198873
TI  - Abeta42/Abeta40 and Abeta42/Abeta38 Ratios Are Associated with Measures of Gait
      Variability and Activities of Daily Living in Mild Alzheimer's Disease: A Pilot
      Study.
AB  - Gait disturbances are some of the earliest changes in dementia and their
      monitoring presents an opportunity for early diagnosis. The exact relationship
      between gait and well-established biomarkers of Alzheimer's disease (AD) remains
      to be clarified. In this study we compared gait-related measures with
      cerebrospinal fluid (CSF) markers of AD pathology. We recruited seventeen
      participants with mild AD in a multi-site study and performed gait assessment as
      well as lumbar punctures to obtain CSF. CSF Abeta42/Abeta40 and Abeta42/Abeta38
      correlated positively with measures of variability (step time and step length) in
      the clinic-based assessments. This was driven by a negative relationship between
      gait variability and Abeta40 and Abeta38 but not Abeta42.The amyloid ratios and
      gait variability measures were also associated with more severe functional
      impairment. We interpret these data as an indication that increasing amyloid
      production (i.e., increasing Abeta40 and Abeta38) is associated with diminishing
      cognitive-motor control of gait. These preliminary results suggest that the two
      amyloid ratios may be a marker of the earliest disturbances in the interplay
      between cognitive and motor control which characterize dementia.

PMID- 30198874
TI  - A Multi-Center Study on Human Brain Glutathione Conformation using Magnetic
      Resonance Spectroscopy.
AB  - Molecular dynamics simulation and in vitro nuclear magnetic resonance (NMR)
      studies on glutathione (GSH) indicated existence of closed and extended
      conformations. The present work in a multi-center research setting reports in
      depth analysis of GSH conformers in vivo using a common magnetic resonance
      spectroscopy (MRS) protocol and signal processing scheme. MEGA-PRESS pulse
      sequence was applied on healthy subjects using 3T Philips MRI scanner (India) and
      3T GE MRI scanner (Norway) using the same experimental parameters (echo time,
      repetition time, and selective 180 degrees  refocusing ON-pulse at 4.40 ppm and
      4.56 ppm). All MRS data were processed at one site National Brain Research Center
      (NBRC) using in-house MRS processing toolbox (KALPANA) for consistency. We have
      found that both the closed and extended GSH conformations are present in human
      brain and the relative proportion of individual conformer peak depends on the
      specific selection of refocusing ON-pulse position in MEGA-PRESS pulse sequence.
      It is important to emphasize that in vivo experiments with different refocusing
      and inversion pulse positions, echo time, and voxel size, clearly evidence the
      presence of both the GSH conformations. The GSH conformer peak positions for the
      closed GSH (Cys-Hbeta) peak at ~2.80 ppm and extended GSH (Cys-Hbeta) peak at
      ~2.95 ppm remain consistent irrespective of the selective refocusing OFF-pulse
      positions. This is the first in vivo study where both extended and closed GSH
      conformers are detected using the MEGA-PRESS sequence employing the parameters
      derived from the high resolution in vitro NMR studies on GSH.

PMID- 30198875
TI  - Huntington's Disease and Employment: The Relative Contributions of Cognitive and
      Motor Decline to the Decision to Leave Work.
AB  - BACKGROUND: Huntington's disease (HD) presents with motor, cognitive, and
      behavioral symptoms that impair functional capacity and the ability to maintain
      employment. The relative contribution of cognitive decline to work disability
      remains controversial. OBJECTIVE: To evaluate the association of cognitive
      decline, compared with motor decline, with the decision to leave work. METHODS:
      Data from the Enroll-HD observational study were analyzed. The correlation of age
      of cognitive symptom onset and age of motor symptom onset with age at leaving
      work was assessed. The association of the Stroop Color Naming Test (SCNT)
      cognitive assessment and the Total Motor Score (TMS) assessment (reverse scored)
      with the Total Functional Capacity (TFC) assessment was also assessed. RESULTS:
      For every year delay in cognitive symptom onset, there was a 0.806 year increase
      in age at leaving work (SE = 0.030, p < 0.001, adj-R2 = 0.628). For every year
      delay of motor symptom onset, there was a 0.814 year increase in age at leaving
      work (SE = 0.031, p < 0.001, adj-R2 = 0.603). For every additional correct SCNT
      response given and for every unit increase in TMS, there was a 0.105 unit
      increase (SE = 0.006, p < 0.001, adj-R2 = 0.315) and a 0.104 unit decrease in TFC
      (SE = 0.003, p < 0.001, adj-R2 = 0.640), respectively. CONCLUSIONS: Cognitive
      symptoms have a significant association, comparable to that of motor symptoms,
      with occupational functioning and the decision to leave work, suggesting that
      development of therapies for both cognitive and motor decline would be important
      for allowing people with HD to remain in the workforce longer.

PMID- 30198877
TI  - The relationship of cervical microbiota diversity with race and disparities in
      preterm birth.
AB  - OBJECTIVE: Pregnant non-Hispanic blacks (NHB) have increased vaginal microbiome
      diversity compared to non-Hispanic whites (NHW) which may contribute to increased
      preterm birth. Cervical microbiome diversity is poorly characterized in
      pregnancy, therefore our objective was to correlate cervical microbiota diversity
      with cervico-vaginal inflammation by race and delivery timing. STUDY DESIGN:
      Pregnant women were recruited in the first and second trimesters. A sterile
      cervical swab and saline lavage were collected at a single time point. Using 16S
      rRNA sequencing, Chao1 and Shannon Diversity (SDI) indicies were measured and
      compared by race and delivery timing (preterm vs. term delivery). Cervico-vaginal
      inflammatory markers were also compared by race and delivery timing. Spearman
      correlation coefficients between cervical microbiome diversity and cervico
      vaginal inflammatory markers were calculated. RESULTS: Of the 51 subjects, 39
      (76%) were NHB and 12 (24%) were NHW. Cervical microbiota SDI was significantly
      higher in NHB compared to NHW (0.5 vs. 0.1; p = 0.03). However, there were no
      difference in Chao1 diversity or cervico-vaginal inflammatory markers by race or
      delivery timing. CONCLUSION: Our findings suggest the cervical microbiota
      diversity during pregnancy differs by race. Larger cohort studies will further
      determine if altered cervical diversity is part of the pathogenesis of PTB and
      explains race disparities.

PMID- 30198878
TI  - A retrospective analysis of paroxysmal sympathetic hyperactivity following severe
      pediatric brain injury.
AB  - BACKGROUND: There are several gaps in the literature related to the prognosis and
      care of children who have experienced a brain injury then develop paroxysmal
      sympathetic hyperactivity (PSH). OBJECTIVE: The objective of the present study
      was to explore the characteristics and prognosis of children who have experienced
      severe brain injury and developed PSH. METHODOLOGY: A secondary analysis was
      conducted using an established clinical dataset of children who had experienced
      severe brain injury and were admitted to an academic children's rehabilitation
      center (n= 83). RESULTS: Those children with PSH had a significantly longer acute
      care length of stay (p= 0.024) and total length of stay (p= 0.034) compared with
      those without PSH. There was no significant difference in cognitive and motor
      function or transition to rehabilitation between those with and those without PSH
      after controlling for age and etiology of injury. IMPLICATIONS: The findings from
      the present study reveal factors regarding the elusive phenomenon of PSH among
      children.

PMID- 30198876
TI  - "Of Mice and Measures": A Project to Improve How We Advance Duchenne Muscular
      Dystrophy Therapies to the Clinic.
AB  - A new line of dystrophic mdx mice on the DBA/2J (D2) background has emerged as a
      candidate to study the efficacy of therapeutic approaches for Duchenne muscular
      dystrophy (DMD). These mice harbor genetic polymorphisms that appear to increase
      the severity of the dystropathology, with disease modifiers that also occur in
      DMD patients, making them attractive for efficacy studies and drug development.
      This workshop aimed at collecting and consolidating available data on the
      pathological features and the natural history of these new D2/mdx mice, for
      comparison with classic mdx mice and controls, and to identify gaps in
      information and their potential value. The overall aim is to establish guidance
      on how to best use the D2/mdx mouse model in preclinical studies.

PMID- 30198879
TI  - Editorials.

PMID- 30198882
TI  - A clinical application of dynamic contrast-enhanced CT (DCE-CT) in patients with
      variously differentiated breast ductal carcinoma.
AB  - PURPOSE: To explore the hemodynamic characteristics of variously differentiated
      breast ductal carcinoma (BDC) using the dynamic contrast-enhanced CT (DCE-CT)
      based CT perfusion imaging (CTPI), including the specific perfusion parameter
      values, and to identify potential clinical applications in the cell
      differentiation degree of BDC. MATERIALS AND METHODS: Forty patients with breast
      ductal carcinoma confirmed by needle puncture biopsy were studied prospectively
      using CTPI on a 64-slice spiral CT scanner. The acquired volume data were used
      for calculations, mapping, and analysis by using a tumor perfusion protocol in
      the CT perfusion software package to measure 4 parameters namely, blood flow
      (BF), blood volume (BV), mean transit time (MTT), and the permeability surface
      (PS) area product. The different differentiated BDC with CT perfusion parameters
      were divided into 3 groups of high, moderate and poor differentiation. The
      comparison among these groups were then made using statistical data analysis
      software. RESULTS: The patients were categorized into three groups of 12, 13, and
      15 highly, moderately and poorly differentiated ductal carcinoma cases,
      respectively. Comparing the perfusion parameters values of the three groups, BF,
      BV, and PS values increased from highly to poorly differentiated BDC cases.
      Differences between the highly and moderately or poorly differentiated groups
      were all statistically significant for BF, BV, and PS values (p <  0.05), while
      MTT value showed no statistical difference among the three groups (p >  0.05).
      CONCLUSION: CTPI is a functional imaging technology from the perspective of
      hemodynamics with potential clinical applications. Three parameters of BF, BV and
      PS values have potential to serve as indicators of the cell differentiation
      degree of the breast ductal carcinoma.

PMID- 30198883
TI  - Structure of the Fc fragment of the NIST reference antibody RM8671.
AB  - As the link between antigen binding and immune activation, the antibody Fc region
      has received extensive structural study. In this report, the structure of the Fc
      fragment of the NIST IgG1 mAb (reference material 8671) is described at 2.1 A
      resolution in space group P212121, with approximate unit-cell parameters a = 50,
      b = 80, c = 138 A. Prior Fc structures with a wide variety of modifications are
      also surveyed, focusing on those in the same crystal form. To facilitate the
      analysis of conformations, a reference frame and a two-parameter metric are
      proposed, considering the CH2 domains as mobile with respect to a fixed dimeric
      CH3 core. Over several human Fc structures, a significant variation in Fc elbow
      conformations is observed, which may serve to facilitate the regulation of Fc
      effector signaling.

PMID- 30198886
TI  - MSMEG_6292, a Mycobacterium smegmatis RNA polymerase secondary channel-binding
      protein: purification, crystallization and X-ray diffraction analysis.
AB  - The transcriptional activity of RNA polymerase (RNAP) is controlled by a diverse
      set of regulatory factors. A subset of these regulators modulate the activity of
      RNAP through its secondary channel. Gre factors reactivate stalled elongation
      complexes by enhancing the intrinsic cleavage activity of RNAP. In the present
      study, the protein MSMEG_6292, a Gre-factor homologue from Mycobacterium
      smegmatis, was expressed heterologously in Escherichia coli and purified using
      standard chromatographic techniques. The hanging-drop vapour-diffusion
      crystallization method yielded diffraction-quality crystals. The crystals
      belonged to the trigonal space group P3121 (or its enantiomorph P3221), with unit
      cell parameters a = b = 83.15, c = 107.07 A, alpha = beta = 90, gamma = 120
      degrees . The crystals diffracted to better than 3.0 A resolution. Molecular
      replacement attempts did not yield any phasing models; hence, platinum
      derivatization was carried out with K2PtCl4 and derivative data were collected to
      3.4 A resolution.

PMID- 30198885
TI  - TssA from Burkholderia cenocepacia: expression, purification, crystallization and
      crystallographic analysis.
AB  - TssA is a core component of the type VI secretion system, and phylogenetic
      analysis of TssA subunits from different species has suggested that these
      proteins fall into three distinct clades. Whilst representatives of two clades,
      TssA1 and TssA2, have been the subjects of investigation, no members of the third
      clade (TssA3) have been studied. Constructs of TssA from Burkholderia
      cenocepacia, a representative of clade 3, were expressed, purified and subjected
      to crystallization trials. Data were collected from crystals of constructs of the
      N-terminal and C-terminal domains. Analysis of the data from the crystals of
      these constructs and preliminary structure determination indicates that the C
      terminal domain forms an assembly of 32 subunits in D16 symmetry, whereas the N
      terminal domain is not involved in subunit assocation.

PMID- 30198884
TI  - Ab initio structure solution of a proteolytic fragment using ARCIMBOLDO.
AB  - Crystal structure determination requires solving the phase problem. This can be
      accomplished using ab initio direct methods for small molecules and
      macromolecules at resolutions higher than 1.2 A, whereas macromolecular structure
      determination at lower resolution requires either molecular replacement using a
      homologous structure or experimental phases using a derivative such as covalent
      labeling (for example selenomethionine or mercury derivatization) or heavy-atom
      soaking (for example iodide ions). Here, a case is presented in which crystals
      were obtained from a 30.8 kDa protein sample and yielded a 1.6 A resolution data
      set with a unit cell that could accommodate approximately 8 kDa of protein. Thus,
      it was unclear what had been crystallized. Molecular replacement with pieces of
      homologous proteins and attempts at iodide ion soaking failed to yield a
      solution. The crystals could not be reproduced. Sequence-independent molecular
      replacement using the structures available in the Protein Data Bank also failed
      to yield a solution. Ultimately, ab initio structure solution proved successful
      using the program ARCIMBOLDO, which identified two alpha-helical elements and
      yielded interpretable maps. The structure was the C-terminal dimerization domain
      of the intended target from Mycobacterium smegmatis. This structure is presented
      as a user-friendly test case in which an unknown protein fragment could be
      determined using ARCIMBOLDO.

PMID- 30198888
TI  - Serendipitous crystallization and structure determination of bacterioferritin
      from Achromobacter.
AB  - Bacterioferritins (Bfrs) are ferritin-like molecules with a hollow spherical 24
      mer complex design that are unique to bacterial and archaeal species. They play a
      critical role in storing iron(III) within the complex at concentrations much
      higher than the feasible solubility limits of iron(III), thus maintaining iron
      homeostasis within cells. Here, the crystal structure of bacterioferritin from
      Achromobacter (Ach Bfr) that crystallized serendipitously during a
      crystallization attempt of an unrelated mycobacterial protein is reported at 1.95
      A resolution. Notably, Fe atoms were bound to the structure along with a
      porphyrin ring sandwiched between the subunits of a dimer. Furthermore, the
      dinuclear ferroxidase center of Ach Bfr has only a single iron bound, in contrast
      to the two Fe atoms in other Bfrs. The structure of Ach Bfr clearly demonstrates
      the substitution of a glutamate residue, which is involved in the interaction
      with the second Fe atom, by a threonine and the consequent absence of another Fe
      atom there. The iron at the dinuclear center has a tetravalent coordination,
      while a second iron with a hexavalent coordination was found within the porphyrin
      ring, generating a heme moiety. Achromobacter spp. are known opportunistic
      pathogens; this structure enhances the current understanding of their iron
      metabolism and regulation, and importantly will be useful in the design of small
      molecule inhibitors against this protein through a structure-guided approach.

PMID- 30198887
TI  - MBP-binding DARPins facilitate the crystallization of an MBP fusion protein.
AB  - The production of high-quality crystals is the main bottleneck in determining the
      structures of proteins using X-ray crystallography. In addition to being
      recognized as a very effective solubility-enhancing fusion partner, Escherichia
      coli maltose-binding protein (MBP) has also been successfully employed as a
      'fixed-arm' crystallization chaperone in more than 100 cases. Here, it is
      reported that designed ankyrin-repeat proteins (DARPins) that bind with high
      affinity to MBP can promote the crystallization of an MBP fusion protein when the
      fusion protein alone fails to produce diffraction-quality crystals. As a proof of
      principle, three different co-crystal structures of MBP fused to the catalytic
      domain of human dual-specificity phosphatase 1 in complex with DARPins are
      reported.

PMID- 30198889
TI  - Staphylococcus aureus lipase: purification, kinetic characterization,
      crystallization and crystallographic study.
AB  - Staphylococcus aureus lipase (SAL), a triacylglycerol esterase, is an important
      virulence factor in S. aureus and may be a therapeutic target for infectious
      diseases caused by S. aureus. For the purposes of anti-SAL drug development using
      structure-based drug design, X-ray crystallographic analysis of SAL overexpressed
      in Escherichia coli was performed. The recombinant protein was purified using a
      three-step protocol involving immobilized metal-affinity chromatography, cation
      exchange chromatography and anion-exchange chromatography flowthrough methods,
      yielding 40 mg of protein per litre of bacterial culture. Crystals were obtained
      using the sitting-drop vapor-diffusion technique. Diffraction data to 3.0 A
      resolution were collected on the BL44XU beamline at SPring-8 at the zinc peak of
      1.2842 A for SAD phasing. The crystals belonged to space group P4122 or P4322,
      with unit-cell parameters a = 131.0, b = 131.0, c = 250.6 A, and are likely to
      contain four SAL molecules (408 residues) per asymmetric unit.

PMID- 30198890
TI  - Mosquito-larvicidal binary toxin receptor protein (Cqm1): crystallization and X
      ray crystallographic analysis.
AB  - Cqm1 from Culex quinquefasciatus has been identified as the receptor for
      Lysinibacillus sphaericus binary toxin (BinAB). It is an amylomaltase that is
      presented on the epithelial membrane in the larval midgut through a glycosyl
      phosphatidylinositol anchor. The active core of this protein (residues 23-560)
      was overexpressed in Escherichia coli, purified and successfully crystallized by
      the sitting-drop vapor-diffusion method using D-arabinose and CaCl2 as additives,
      as identified using high-throughput differential scanning fluorimetry analysis. X
      ray diffraction data were collected to a resolution of 2.8 A using a laboratory X
      ray source. The crystals had the symmetry of space group P212121, with unit-cell
      parameters a = 191.3, b = 205.3, c = 59.0 A and with four monomers in the
      asymmetric unit. Structure refinement is in progress. This is the first structure
      report for a binary toxin receptor and for a member of the GH13_17 subfamily in
      the CAZy database.

PMID- 30198891
TI  - TssA from Aeromonas hydrophila: expression, purification and crystallographic
      studies.
AB  - TssA is a core subunit of the type VI secretion system, which is a major player
      in interspecies competition in Gram-negative bacteria. Previous studies on
      enteroaggregative Escherichia coli TssA suggested that it is comprised of three
      putative domains: a conserved N-terminal domain, a middle domain and a ring
      forming C-terminal domain. X-ray studies of the latter two domains have
      identified their respective structures. Here, the results of the expression and
      purification of full-length and domain constructs of TssA from Aeromonas
      hydrophila are reported, resulting in diffraction-quality crystals for the middle
      domain (Nt2) and a construct including the middle and C-terminal domains (Nt2
      CTD).

PMID- 30198892
TI  - X-ray structure of alisporivir in complex with cyclophilin A at 1.5 A resolution.
AB  - Alisporivir (ALV) is an 11-amino-acid hydrophobic cyclic peptide with N-methyl-D
      alanine and N-ethyl-L-valine (NEV) residues at positions 3 and 4, respectively.
      ALV is a non-immunosuppressive cyclosporin A (CsA) derivative. This inhibitor
      targets cyclophilins (Cyps), a family of proteins with peptidyl-prolyl cis/trans
      isomerase enzymatic activity. Cyps act as protein chaperones and are involved in
      numerous cellular functions. Moreover, Cyps have been shown to be an essential
      cofactor for the replication of many viruses, including Hepatitis C virus and
      Human immunodeficiency virus, and have also been shown to be involved in
      mitochondrial diseases. For these reasons, cyclophilins represent an attractive
      drug target. The structure of ALV in complex with cyclophilin A (CypA), the most
      abundant Cyp in humans, has been determined at 1.5 A resolution. This first
      structure of the CypA-ALV complex shows that the binding of ALV is highly similar
      to that of CsA. The high resolution allowed the unambiguous determination of the
      conformations of residues 3 and 4 in ALV when bound to its target. In particular,
      the side-chain conformation of NEV4 precludes the interaction of the CypA-ALV
      complex with calcineurin, a cellular protein phosphatase involved in the immune
      response, which explains the non-immunosuppressive property of ALV. This study
      provides detailed molecular insights into the CypA-ALV interaction.

PMID- 30198893
TI  - Investigation into the binding of dyes within protein crystals.
AB  - It was found that the crystals of at least a dozen different proteins could be
      thoroughly stained to an intense color with a panel of dyes. Many, if not most,
      of the stained protein crystals retained the dyes almost indefinitely when placed
      in large volumes of dye-free mother liquor. Dialysis experiments showed that most
      of the dyes that were retained in crystals also bound to the protein when free in
      solution; less frequently, some dyes bound only in the crystal. The experiments
      indicated a strong association of the dyes with the proteins. Four protein
      crystals were investigated by X-ray diffraction to ascertain the mode of binding.
      These were crystals of lysozyme, thaumatin, trypsin inhibited with benzamidine
      and satellite tobacco mosaic virus. In 30 X-ray analyses of protein crystal-dye
      complexes, in only three difference Fourier maps was any difference electron
      density present that was consistent with the binding of dye molecules, and even
      in these three cases (thaumatin plus thioflavin T, xylene cyanol and m-cresol
      purple) the amount of dye observed was inadequate to explain the intense color of
      the crystals. It was concluded that the dye molecules, which are clearly inside
      the crystals, are disordered but are paradoxically tightly bound to the protein.
      It is speculated that the dyes, which exhibit large hydrophobic cores and
      peripheral charged groups, may interact with the crystalline proteins in the
      manner of conventional detergents.

PMID- 30198896
TI  - Crystal structure of the Acinetobacter baumannii outer membrane protein Omp33.
AB  - Acinetobacter baumannii is becoming a major threat to human health due to its
      multidrug resistance. This is owing in a large part to the low permeability of
      its outer membrane (OM), which prevents high internal antibiotic concentrations
      and makes antibiotic-resistance mechanisms more effective. To exploit OM channels
      as potential delivery vehicles for future antibiotics, structural information is
      required. One abundant OM protein in A. baumannii is Omp33. This protein has been
      reported to be important for the in vivo fitness and virulence of A. baumannii,
      but its structure is not known. Here, the X-ray crystal structure of Omp33 is
      reported at a resolution of 2.1 A. Omp33 has a 14-beta-stranded barrel without
      stable extracellular loop constrictions. Instead, an extended and unusual
      periplasmic turn connecting beta-strands 2 and 3 is present, which folds into the
      pore lumen and completely blocks the aqueous channel. The Omp33 structure helps
      in understanding how A. baumannii OM proteins contribute to the low permeability
      of the cell envelope of this bacterium and suggests that Omp33 might function as
      a gated channel.

PMID- 30198894
TI  - New tools for the analysis and validation of cryo-EM maps and atomic models.
AB  - Recent advances in the field of electron cryomicroscopy (cryo-EM) have resulted
      in a rapidly increasing number of atomic models of biomacromolecules that have
      been solved using this technique and deposited in the Protein Data Bank and the
      Electron Microscopy Data Bank. Similar to macromolecular crystallography,
      validation tools for these models and maps are required. While some of these
      validation tools may be borrowed from crystallography, new methods specifically
      designed for cryo-EM validation are required. Here, new computational methods and
      tools implemented in PHENIX are discussed, including d99 to estimate resolution,
      phenix.auto_sharpen to improve maps and phenix.mtriage to analyze cryo-EM maps.
      It is suggested that cryo-EM half-maps and masks should be deposited to
      facilitate the evaluation and validation of cryo-EM-derived atomic models and
      maps. The application of these tools to deposited cryo-EM atomic models and maps
      is also presented.

PMID- 30198895
TI  - Crystal structure of the post-fusion core of the Human coronavirus 229E spike
      protein at 1.86 A resolution.
AB  - Human coronavirus 229E (HCoV-229E) usually causes mild upper respiratory
      infections in heathy adults, but may lead to severe complications or mortality in
      individuals with weakened immune systems. Virus entry of HCoV-229E is mediated by
      its spike (S) protein, where the S1 domain facilitates attachment to host cells
      and the S2 domain is involved in subsequent fusion of the virus and host
      membranes. During the fusion process, two heptad repeats, HR1 and HR2, in the S2
      domain assemble into a six-helix membrane-fusion structure termed the fusion
      core. Here, the complete fusion-core structure of HCoV-229E has been determined
      at 1.86 A resolution, representing the most complete post-fusion conformation
      thus far among published human alphacoronavirus (alpha-HCoV) fusion-core
      structures. The overall structure of the HCoV-229E fusion core is similar to
      those of SARS, MERS and HCoV-NL63, but the packing of its 3HR1 core differs from
      those of SARS and MERS in that it contains more noncanonical 'x' and 'da' layers.
      Side-by-side electrostatic surface comparisons reveal that the electrostatic
      surface potentials are opposite in alpha-HCoVs and beta-HCoVs at certain
      positions and that the HCoV-229E surface also appears to be the most hydrophobic
      among the various HCoVs. In addition to the highly conserved hydrophobic
      interactions between HR1 and HR2, some polar and electrostatic interactions are
      also well preserved across different HCoVs. This study adds to the structural
      profiling of HCoVs to aid in the structure-based design of pan-coronavirus small
      molecules or peptides to inhibit viral fusion.

PMID- 30198897
TI  - Structure and function of L-threonine-3-dehydrogenase from the parasitic
      protozoan Trypanosoma brucei revealed by X-ray crystallography and geometric
      simulations.
AB  - Two of the world's most neglected tropical diseases, human African
      trypanosomiasis (HAT) and Chagas disease, are caused by protozoan parasites of
      the genus Trypanosoma. These organisms possess specialized metabolic pathways,
      frequently distinct from those in humans, which have potential to be exploited as
      novel drug targets. This study elucidates the structure and function of L
      threonine-3-dehydrogenase (TDH) from T. brucei, the causative pathogen of HAT.
      TDH is a key enzyme in the metabolism of L-threonine, and an inhibitor of TDH has
      been shown to have trypanocidal activity in the procyclic form of T. brucei. TDH
      is a nonfunctional pseudogene in humans, suggesting that it may be possible to
      rationally design safe and specific therapies for trypanosomiasis by targeting
      this parasite enzyme. As an initial step, the TDH gene from T. brucei was
      expressed and the three-dimensional structure of the enzyme was solved by X-ray
      crystallography. In multiple crystallographic structures, T. brucei TDH is
      revealed to be a dimeric short-chain dehydrogenase that displays a considerable
      degree of conformational variation in its ligand-binding regions. Geometric
      simulations of the structure have provided insight into the dynamic behaviour of
      this enzyme. Furthermore, structures of TDH bound to its natural substrates and
      known inhibitors have been determined, giving an indication of the mechanism of
      catalysis of the enzyme. Collectively, these results provide vital details for
      future drug design to target TDH or related enzymes.

PMID- 30198898
TI  - Improving signal strength in serial crystallography with DIALS geometry
      refinement.
AB  - The DIALS diffraction-modeling software package has been applied to serial
      crystallography data. Diffraction modeling is an exercise in determining the
      experimental parameters, such as incident beam wavelength, crystal unit cell and
      orientation, and detector geometry, that are most consistent with the observed
      positions of Bragg spots. These parameters can be refined by nonlinear least
      squares fitting. In previous work, it has been challenging to refine both the
      positions of the sensors (metrology) on multipanel imaging detectors such as the
      CSPAD and the orientations of all of the crystals studied. Since the optimal
      models for metrology and crystal orientation are interdependent, alternate cycles
      of panel refinement and crystal refinement have been required. To simplify the
      process, a sparse linear algebra technique for solving the normal equations was
      implemented, allowing the detector panels to be refined simultaneously against
      the diffraction from thousands of crystals with excellent computational
      performance. Separately, it is shown how to refine the metrology of a second
      CSPAD detector, positioned at a distance of 2.5 m from the crystal, used for
      recording low-angle reflections. With the ability to jointly refine the detector
      position against the ensemble of all crystals used for structure determination,
      it is shown that ensemble refinement greatly reduces the apparent nonisomorphism
      that is often observed in the unit-cell distributions from still-shot serial
      crystallography. In addition, it is shown that batching the images by timestamp
      and re-refining the detector position can realistically model small, time
      dependent variations in detector position relative to the sample, and thereby
      improve the integrated structure-factor intensity signal and heavy-atom anomalous
      peak heights.

PMID- 30198900
TI  - The crystal structure of an essential high-temperature requirement protein HtrA1
      (Rv1223) from Mycobacterium tuberculosis reveals its unique features.
AB  - High-temperature requirement A (HtrA) proteins, which are members of the heat
      shock-induced serine protease family, are involved in extracytoplasmic protein
      quality control and bacterial survival strategies under stress conditions, and
      are associated with the virulence of several pathogens; they are therefore major
      drug targets. Mycobacterium tuberculosis possesses three putative HtrAs: HtrA1
      (Rv1223), HtrA2 (Rv0983) and HtrA3 (Rv0125). Each has a cytoplasmic region, a
      transmembrane helix and a periplasmic region. Here, the crystal structure of the
      periplasmic region consisting of a protease domain (PD) and a PDZ domain from an
      M. tuberculosis HtrA1 mutant (mHtrA1S387A) is reported at 2.7 A resolution.
      Although the mHtrA1S387A PD shows structural features similar to those of other
      HtrAs, its loops, particularly L3 and LA, display different conformations. Loop
      L3 communicates between the PDs of the trimer and the PDZ domains and undergoes a
      transition from an active to an inactive conformation, as reported for an
      equivalent HtrA (DegS). Loop LA, which is responsible for higher oligomer
      formation owing to its length (50 amino acids) in DegP, is very short in
      mHtrA1S387A (five amino acids), as in mHtrA2 (also five amino acids), and
      therefore lacks essential interactions for the formation of higher oligomers.
      Notably, a well ordered loop known as the insertion clamp in the PDZ domain
      interacts with the protease domain of the adjacent molecule, which possibly aids
      in the stabilization of a trimeric functional unit of this enzyme. The three
      dimensional structure of mHtrA1S387A presented here will be useful in the design
      of enzyme-specific antituberculosis inhibitors.

PMID- 30198899
TI  - High-pressure protein crystal structure analysis of Escherichia coli
      dihydrofolate reductase complexed with folate and NADP.
AB  - A high-pressure crystallographic study was conducted on Escherichia coli
      dihydrofolate reductase (ecDHFR) complexed with folate and NADP+ in crystal forms
      containing both the open and closed conformations of the M20 loop under high
      pressure conditions of up to 800 MPa. At pressures between 270 and 500 MPa the
      crystal form containing the open conformation exhibited a phase transition from
      P21 to C2. Several structural changes in ecDHFR were observed at high pressure
      that were also accompanied by structural changes in the NADP+ cofactor and the
      hydration structure. In the crystal form with the closed conformation the M20
      loop moved as the pressure changed, with accompanying conformational changes
      around the active site, including NADP+ and folate. These movements were
      consistent with the suggested hypothesis that movement of the M20 loop was
      necessary for ecDHFR to catalyze the reaction. In the crystal form with the open
      conformation the nicotinamide ring of the NADP+ cofactor undergoes a large flip
      as an intermediate step in the reaction, despite being in a crystalline state.
      Furthermore, observation of the water molecules between Arg57 and folate
      elucidated an early step in the substrate-binding pathway. These results
      demonstrate the possibility of using high-pressure protein crystallography as a
      method to capture high-energy substates or transient structures related to the
      protein reaction cycle.

PMID- 30198902
TI  - Crystallographically correct but confusing presentation of structural models
      deposited in the Protein Data Bank.
AB  - The Protein Data Bank (PDB) constitutes a collection of the available atomic
      models of macromolecules and their complexes obtained by various methods used in
      structural biology, but chiefly by crystallography. It is an indispensable
      resource for all branches of science that deal with the structures of
      biologically active molecules, such as structural biology, bioinformatics, the
      design of novel drugs etc. Since not all users of the PDB are familiar with the
      methods of crystallography, it is important to present the results of
      crystallographic analyses in a form that is easy to interpret by nonspecialists.
      It is advisable during the submission of structures to the PDB to pay attention
      to the optimal placement of molecules within the crystal unit cell, to the
      correct representation of oligomeric assemblies and to the proper selection of
      the space-group symmetry. Examples of significant departures from these
      principles illustrate the potential for the misinterpretation of such
      suboptimally presented crystal structures.

PMID- 30198903
TI  - Targeting the aryl hydrocarbon receptor/polyamine biosynthesis axis of evil for
      cancer therapy.
AB  - The polyamine metabolic pathway has been considered a rational target for
      antineoplastic therapy since it was discovered that polyamines are absolute
      requirements for tumor initiation, growth, and, in some instances, survival.
      Although several promising preclinical studies have demonstrated the critical
      nature of polyamines for tumor growth, the clinical success of agents targeting
      polyamine metabolism have been lacking. In the accompanying article, Bianchi
      Smiraglia et al. identify both a new target and new drug that inhibits polyamine
      biosynthesis, reduces intracellular polyamines, and inhibits the growth of
      several models of human multiple myeloma. These results are both intriguing and
      provide promise for moving such a strategy to the clinic.

PMID- 30198901
TI  - The impact of cryosolution thermal contraction on proteins and protein crystals:
      volumes, conformation and order.
AB  - Cryocooling of macromolecular crystals is commonly employed to limit radiation
      damage during X-ray diffraction data collection. However, cooling itself affects
      macromolecular conformation and often damages crystals via poorly understood
      processes. Here, the effects of cryosolution thermal contraction on
      macromolecular conformation and crystal order in crystals ranging from 32 to 67%
      solvent content are systematically investigated. It is found that the solution
      thermal contraction affects macromolecule configurations and volumes, unit-cell
      volumes, crystal packing and crystal order. The effects occur through not only
      thermal contraction, but also pressure caused by the mismatched contraction of
      cryosolvent and pores. Higher solvent-content crystals are more affected. In some
      cases the solvent contraction can be adjusted to reduce mosaicity and increase
      the strength of diffraction. Ice formation in some crystals is found to cause
      damage via a reduction in unit-cell volume, which is interpreted through solvent
      transport out of unit cells during cooling. The results point to more deductive
      approaches to cryoprotection optimization by adjusting the cryosolution
      composition to reduce thermal contraction-induced stresses in the crystal with
      cooling.

PMID- 30198905
TI  - No recovery of replication-competent HIV-1 from human liver macrophages.
AB  - Long-lived HIV-1 reservoirs that persist despite antiretroviral therapy (ART) are
      a major impediment to a cure for HIV-1. We examined whether human liver
      macrophages (LMs), the largest tissue macrophage population, comprise an HIV-1
      reservoir. We purified LMs from liver explants and included treatment with a T
      cell immunotoxin to reduce T cells to 1% or less. LMs were purified from 9 HIV-1
      infected persons, 8 of whom were on ART (range 8-140 months). Purified LMs were
      stimulated ex vivo and supernatants from 6 of 8 LMs from persons on ART
      transmitted infection. However, HIV-1 propagation from LMs was not sustained
      except in LMs from 1 person taking ART for less than 1 year. Bulk liver sequences
      matched LM-derived HIV-1 in 5 individuals. Additional in vitro experiments
      undertaken to quantify the decay of HIV-1-infected LMs from 3 healthy controls
      showed evidence of infection and viral release for prolonged durations (>170
      days). Released HIV-1 propagated robustly in target cells, demonstrating that
      viral outgrowth was observable using our methods. The t1/2 of HIV-1-infected LMs
      ranged from 3.8-55 days. These findings suggest that while HIV-1 persists in LMs
      during ART, it does so in forms that are inert, suggesting that they are
      defective or restricted with regard to propagation.

PMID- 30198906
TI  - Long noncoding RNA LERFS negatively regulates rheumatoid synovial aggression and
      proliferation.
AB  - Fibroblast-like synoviocytes (FLSs) are critical to synovial aggression and joint
      destruction in rheumatoid arthritis (RA). The role of long noncoding RNAs
      (lncRNAs) in RA is largely unknown. Here, we identified a lncRNA, LERFS (lowly
      expressed in rheumatoid fibroblast-like synoviocytes), that negatively regulates
      the migration, invasion, and proliferation of FLSs through interaction with
      heterogeneous nuclear ribonucleoprotein Q (hnRNP Q). Under healthy conditions, by
      binding to the mRNA of RhoA, Rac1, and CDC42 - the small GTPase proteins that
      control the motility and proliferation of FLSs - the LERFS-hnRNP Q complex
      decreased the stability or translation of target mRNAs and downregulated their
      protein levels. But in RA FLSs, decreased LERFS levels induced a reduction of the
      LERFS-hnRNP Q complex, which reduced the binding of hnRNP Q to target mRNA and
      therefore increased the stability or translation of target mRNA. These findings
      suggest that a decrease in synovial LERFS may contribute to synovial aggression
      and joint destruction in RA and that targeting the lncRNA LERFS may have
      therapeutic potential in patients with RA.

PMID- 30198904
TI  - Contribution of NK cells to immunotherapy mediated by PD-1/PD-L1 blockade.
AB  - Checkpoint blockade immunotherapy targeting the PD-1/PD-L1 inhibitory axis has
      produced remarkable results in the treatment of several types of cancer. Whereas
      cytotoxic T cells are known to provide important antitumor effects during
      checkpoint blockade, certain cancers with low MHC expression are responsive to
      therapy, suggesting that other immune cell types may also play a role. Here, we
      employed several mouse models of cancer to investigate the effect of PD-1/PD-L1
      blockade on NK cells, a population of cytotoxic innate lymphocytes that also
      mediate antitumor immunity. We discovered that PD-1 and PD-L1 blockade elicited a
      strong NK cell response that was indispensable for the full therapeutic effect of
      immunotherapy. PD-1 was expressed on NK cells within transplantable, spontaneous,
      and genetically induced mouse tumor models, and PD-L1 expression in cancer cells
      resulted in reduced NK cell responses and generation of more aggressive tumors in
      vivo. PD-1 expression was more abundant on NK cells with an activated and more
      responsive phenotype and did not mark NK cells with an exhausted phenotype. These
      results demonstrate the importance of the PD-1/PD-L1 axis in inhibiting NK cell
      responses in vivo and reveal that NK cells, in addition to T cells, mediate the
      effect of PD-1/PD-L1 blockade immunotherapy.

PMID- 30198911
TI  - Impact of Change in Body Mass Index on Outcomes After Left Ventricular Assist
      Device Implantation in Obese Patients.
AB  - Obesity could be a risk factor portending a poor prognosis after left ventricular
      assist device (LVAD) implantation. We sought to determine the impact of change in
      body mass index (BMI) on outcomes in obese patients supported by LVAD. Fifty-nine
      patients, who received LVAD between January 2010 and June 2015, with BMI >=30
      kg/m at the time of LVAD implantation, were retrospectively analyzed. Patients
      were divided into two groups based upon whether BMI after 6 months of device
      support decreased when compared with before. Thirty-eight patients who
      experienced decrease in BMI (group D) were compared with 21 patients whose BMI
      increased (group I). Baseline characteristics were similar between the groups
      except for body weight and BMI, which were significantly higher in group D (BMI:
      35.9 +/- 4.0 kg/m vs. 33.4 +/- 3.5 kg/m; p = 0.018). During mean follow-up of 560
      +/- 178 days, group I had significantly higher incidence of infection [events per
      patient-years (eppy): nondevice related: 0.18 vs. 0.35, p = 0.01; device related:
      0.1 vs. 0.32, p < 0.01; sepsis: 0.1 vs. 0.32, p < 0.01], heart failure (eppy: 0.1
      vs. 0.25, p < 0.01), and renal failure (eppy: 0.03 vs. 0.14, p < 0.01). Survival
      at 2 years was significantly lower in group I (84.8% vs. 57.1%, p = 0.025).
      Increase in BMI in obese patients on LVAD is associated with worse survival with
      a higher incidence of infection, heart failure, and renal failure. Weight control
      may be a modifiable factor to improve prognosis.

PMID- 30198909
TI  - NK cells for PD-1/PD-L1 blockade immunotherapy: pinning down the NK cell.
AB  - In spite of a very robust body of literature and definitive data demonstrating
      the importance of the programmed cell death receptor-1 (PD-1) pathway in T cells
      and their function, the data on NK cell PD-1 expression have been highly variable
      and, particularly in the case of mouse NK cells, scarce. In this issue of the
      JCI, Hsu et al. present data demonstrating PD-1 expression on mouse NK cells only
      within tumors and show that PD-1 blockade elicits an antitumor NK cell-mediated
      response. This study indicates that, given the complexity of both the biology and
      study of NK cells, further work is needed to more clearly determine the role of
      the PD-1/PD-1 ligand (PD-L1) on NK cells.

PMID- 30198907
TI  - PD-1+CD8+ T cells are clonally expanding effectors in human chronic inflammation.
AB  - Chronic inflammatory diseases are characterized by recurrent inflammatory attacks
      in the tissues mediated by autoreactive T cells. Identity and functional
      programming of CD8+ T cells at the target site of inflammation still remain
      elusive. One key question is whether, in these antigen-rich environments, chronic
      stimulation leads to CD8+ T cell exhaustion comparable to what is observed in
      infectious disease contexts. In the synovial fluid (SF) of juvenile idiopathic
      arthritis (JIA) patients, a model of chronic inflammation, an overrepresentation
      of PD-1+CD8+ T cells was found. Gene expression profiling, gene set enrichment
      analysis, functional studies, and extracellular flux analysis identified PD
      1+CD8+ T cells as metabolically active effectors, with no sign of exhaustion.
      Furthermore, PD-1+CD8+ T cells were enriched for a tissue-resident memory (Trm)
      cell transcriptional profile and demonstrated increased clonal expansion compared
      with the PD-1- counterpart, suggesting antigen-driven expansion of locally
      adapted cells. Interestingly, this subset was also found increased in target
      tissues in other human chronic inflammatory diseases. These data indicate that
      local chronic inflammation drives the induction and expansion of CD8+ T cells
      endowed with potential detrimental properties. Together, these findings lay the
      basis for investigation of PD-1-expressing CD8+ T cell targeting strategies in
      human chronic inflammatory diseases.

PMID- 30198912
TI  - THE EFFECT OF STATIC STRETCHING OF PERONEAL AND TIBIAL MUSCLES ON THE REACTION
      TIME: A RANDOMIZED CONTROLLED STUDY.
AB  - OBJECTIVE: The aim of this study is to investigate the acute and chronic effects
      of static stretching on peroneal and tibialis anterior reaction characteristics.
      DESIGN: All 23 participants who volunteered for this study were randomly divided
      into static (n=12) and control (n=11) groups. The subjects in the static
      stretching group performed stretching exercises for the ankle evertor and
      dorsiflexor muscles 5 days a week for 6 weeks. Peroneal and tibial muscle
      reaction characteristics were evaluated at the beginning (2 times for acute
      effect) and end of this period. Electromyographic activity parameters of the
      muscles were measured using an ankle inversion tilting platform that simulated a
      sudden ankle inversion. There were four different ankle inversion conditions: (a)
      ankle-neutral, 15 degrees  inversion; (b) ankle-neutral, 30 degrees  inversion;
      (c) ankle-20 degrees  plantarflexion, 15 degrees  inversion; and (d) ankle-20
      degrees  plantarflexion, 30 degrees  inversion. RESULTS: Either in terms of acute
      or chronic effects, no significant differences were found following static
      stretching exercises for peroneal and tibial muscle reaction time, reaction
      duration and muscle activity evaluated in 4 positions on the ankle inversion
      simulation platform (p>0.05). CONCLUSION: In light of these results, it is
      possible to state that short duration of static stretching exercises can still be
      applied before sports activities.

PMID- 30198913
TI  - Ultrasound-Guided Botulinum Toxin Injections in Cervical Dystonia Needs Prompt
      Muscle Selection, Appropriate Dosage and Precise Guidance.

PMID- 30198914
TI  - Effects of 9-cis-retinoic acid on the proliferation and apoptosis of cutaneous T
      cell lymphoma cells.
AB  - The vitamin A derivative 9-cis-retinoic acid (9-cis-RA) has been used for the
      treatment and prevention of cutaneous T-cell lymphoma (CTCL). However, the
      precise mechanism by which 9-cis-RA treatment ameliorates CTCL remains elusive.
      Our research shows that 9-cis-RA inhibits proliferation and induces apoptosis in
      CTCL cells in a dose-dependent and time-dependent manner. 9-Cis-RA also induced
      G0/G1 cell cycle arrest by downregulation of cyclin D1. We confirmed that 9-cis
      RA significantly decreased phosphorylation of JAK1, STAT3, and STAT5 and
      downregulated Bcl-xL and cyclin D1, indicating that 9-cis-RA inhibited the
      activation of JAK/STAT signaling. Meanwhile, 9-cis-RA also activated classical RA
      mediated transcription by retinoic acid receptors (RAR) and/or retinoid X
      receptors (RXR) in a CTCL cell line. Thus, 9-cis-RA may be effective for
      chemotherapy and may prevent human CTCL by inhibiting proliferation and inducing
      apoptosis by inhibition of the JAK/STAT pathway and activation of the RAR/RXR
      pathway.

PMID- 30198908
TI  - Inhibition of the aryl hydrocarbon receptor/polyamine biosynthesis axis
      suppresses multiple myeloma.
AB  - Polyamine inhibition for cancer therapy is, conceptually, an attractive approach
      but has yet to meet success in the clinical setting. The aryl hydrocarbon
      receptor (AHR) is the central transcriptional regulator of the xenobiotic
      response. Our study revealed that AHR also positively regulates intracellular
      polyamine production via direct transcriptional activation of 2 genes, ODC1 and
      AZIN1, which are involved in polyamine biosynthesis and control, respectively. In
      patients with multiple myeloma (MM), AHR levels were inversely correlated with
      survival, suggesting that AHR inhibition may be beneficial for the treatment of
      this disease. We identified clofazimine (CLF), an FDA-approved anti-leprosy drug,
      as a potent AHR antagonist and a suppressor of polyamine biosynthesis.
      Experiments in a transgenic model of MM (Vk*Myc mice) and in immunocompromised
      mice bearing MM cell xenografts revealed high efficacy of CLF comparable to that
      of bortezomib, a first-in-class proteasome inhibitor used for the treatment of
      MM. This study identifies a previously unrecognized regulatory axis between AHR
      and polyamine metabolism and reveals CLF as an inhibitor of AHR and a potentially
      clinically relevant anti-MM agent.

PMID- 30198910
TI  - Pseudomonas aeruginosa utilizes host polyunsaturated phosphatidylethanolamines to
      trigger theft-ferroptosis in bronchial epithelium.
AB  - Ferroptosis is a death program executed via selective oxidation of arachidonic
      acid-phosphatidylethanolamines (AA-PE) by 15-lipoxygenases. In mammalian cells
      and tissues, ferroptosis has been pathogenically associated with brain, kidney,
      and liver injury/diseases. We discovered that a prokaryotic bacterium,
      Pseudomonas aeruginosa, that does not contain AA-PE can express lipoxygenase
      (pLoxA), oxidize host AA-PE to 15-hydroperoxy-AA-PE (15-HOO-AA-PE), and trigger
      ferroptosis in human bronchial epithelial cells. Induction of ferroptosis by
      clinical P. aeruginosa isolates from patients with persistent lower respiratory
      tract infections was dependent on the level and enzymatic activity of pLoxA.
      Redox phospholipidomics revealed elevated levels of oxidized AA-PE in airway
      tissues from patients with cystic fibrosis (CF) but not with emphysema or CF
      without P. aeruginosa. We believe that the evolutionarily conserved mechanism of
      pLoxA-driven ferroptosis may represent a potential therapeutic target against P.
      aeruginosa-associated diseases such as CF and persistent lower respiratory tract
      infections.

PMID- 30198915
TI  - Genitoanal Injury in Sexually Assaulted Adult Women: Six-Year Retrospective in
      Bangkok.
AB  - Sexual assault persists as a global problem. Even when sexual assault does not
      result in obvious visible wounds, genitoanal injury must be evaluated because it
      is often pertinent for legal outcomes. Macroscopic ("naked eye") examination is
      valuable when colposcope is not available or when patients do not consent. This
      study reviewed the genitoanal injuries of 117 sexually assaulted adult women
      evaluated macroscopically. Genitoanal injury prevalence was 47%, and
      nongenitoanal injury prevalence was at 44%. The most common injury type was
      abrasion, and the most common site was posterior fourchette. Most injury patterns
      were singular. The number of women who did not report a history of sexual
      intercourse in the sample and usage of fingers/palm during assault may have
      affected pattern and/or injury type. There was a significant relationship between
      hymenal old tear below the 3- to 9-o'clock area and prior sexual intercourse.
      Factors related to genitoanal injury were prior sexual intercourse, vaginal
      delivery, and spermatozoa detection. In conclusion, all sexually assaulted women
      should be encouraged to have a pelvic examination: nothing overtly visible does
      not mean that nothing happened.

PMID- 30198916
TI  - Postmortem Hyperthermia: Two Case Reports and a Review of the Literature.
AB  - In this daily practice, the forensic pathologist is rarely confronted with
      postmortem hyperthermia associated with the rapid onset of rigor mortis. We
      report 2 similar cases where the rectal temperature value taken during the on
      scene investigations by the forensic pathologist was greater than 40 degrees C
      (104 degrees F) in both cases, and rigor mortis was complete within less than 6
      hours postmortem. The first case was due to a deadly intoxication by ecstasy and
      the second one to the deadly association of methadone and a possible neuroleptic
      malignant syndrome. Infection-related deaths were eliminated. Thus, the
      association of postmortem hyperthermia and rapid-onset rigor mortis would suggest
      in the first hypothesis a toxic death, particularly 3,4
      methylenedioxymethamphetamine. However, an autopsy and toxicological analysis are
      necessary to confirm the cause of death.

PMID- 30198918
TI  - The Role of Centers of Excellence With Multidisciplinary Teams in the Management
      of Abnormal Invasive Placenta.
AB  - Abnormal invasive placenta (AIP) causes significant maternal and perinatal
      morbidity and mortality. With the increasing incidence of cesarean delivery, this
      condition is dramatically more common in the last 20 years. Advances in grayscale
      and Doppler ultrasound have facilitated prenatal diagnosis of abnormal
      placentation to allow the development of multidisciplinary management plans.
      Outcomes are improved when delivery is accomplished in centers with
      multidisciplinary expertise and experience in the care of AIP. This article
      highlights the desired features for developing and managing a multidisciplinary
      team dedicated to the treatment of AIP in center of excellence.

PMID- 30198917
TI  - Regulation of muscle atrophy by microRNAs: 'AtromiRs' as potential target in
      cachexia.
AB  - PURPOSE OF REVIEW: To provide an overview and describe the mode of action of
      miRNAs recently implicated in muscle atrophy, and discuss the challenges to
      explore their potential as putative therapeutic targets in cachexia. RECENT
      FINDINGS: Recent work showed differentially expressed miRNAs in skeletal muscle
      of patients with cachexia-associated diseases. Studies using experimental models
      revealed miRNA regulation of the anabolic IGF-1 and catabolic TGF- beta/myostatin
      pathways, and downstream protein synthesis and proteolysis signaling in control
      of muscle mass. SUMMARY: Cachexia is a complex metabolic condition associated
      with progressive body weight loss, wasting of skeletal muscle mass and decrease
      in muscle strength. MiRNAs play a central role in post-transcriptional gene
      regulation by targeting mRNAs, thereby coordinating and fine-tuning many cellular
      processes. MiRNA expression profiling studies of muscle biopsies have revealed
      differentially expressed miRNAs in patients with low muscle mass or cachexia.
      Evaluation in experimental models has revealed muscle atrophy, inhibition of
      protein synthesis and activation of proteolysis in response to modulation of
      specific miRNAs, termed 'atromiRs' in this review. These exciting findings call
      for further studies aimed at exploring the conservation of differentially
      expressed miRNAs across diseases accompanied by cachexia, identification of miRNA
      clusters and targets involved in muscle atrophy, and probing whether these miRNAs
      might be potential therapeutic targets for cachexia.

PMID- 30198919
TI  - Intraoperative Mortality in Malawi.
AB  - BACKGROUND: Surgical care is essential to improving population health, but
      metrics to monitor and evaluate the continuum of surgical care delivery have
      rarely been applied in low-resource settings, and improved efforts at
      benchmarking progress are needed. The objective of this study was to measure the
      intraoperative mortality at a Central Referral Hospital in Malawi, evaluate
      whether there have been changes in intraoperative mortality between 2 time
      periods, and assess factors associated with intraoperative mortality. METHODS:
      This was a retrospective cohort study of patients undergoing surgery at Kamuzu
      Central Hospital in Lilongwe, Malawi. Data describing daily consecutive operative
      cases were collected prospectively during 2 time periods: 2004-2006 (early
      cohort) and 2015-2016 (late cohort). The primary outcome was intraoperative
      mortality. Inverse probability of treatment weighting was used to analyze the
      association of intraoperative mortality with time using logistic regression
      models. Multivariable logistic models were performed to evaluate factors
      associated with intraoperative mortality. RESULTS: There were 21,090 surgeries
      performed during the 2 time periods, with 15,846 (75%) and 5244 (25%) completed
      from 2004 to 2006 and 2015 to 2016, respectively. Intraoperative mortality in the
      early cohort was 57 deaths per 100,000 surgeries (95% confidence interval [CI],
      26-108) and in the late cohort was 133 per 100,000 surgeries (95% CI, 56-286),
      with 76 per 100,000 surgeries (95% CI, 44-124) overall. After applying inverse
      probability of treatment weighting, there was no evidence of an association
      between time periods and intraoperative mortality (odds ratio [OR], 1.6; 95% CI,
      0.9-2.8; P = .08). Factors associated with intraoperative mortality, adjusting
      for demographics, included American Society of Anesthesiology physical status III
      or IV versus I or II (OR, 4.4; 95% CI, 1.5-12.5; P = .006) and emergency versus
      elective surgery (OR, 7.7; 95% CI, 2.5-23.6; P < .001). CONCLUSIONS:
      Intraoperative mortality in the study hospital in Malawi is high and has not
      improved over time. These data demonstrate an urgent need to improve the safety
      and quality of perioperative care in developing countries and integrate
      perioperative care into global health efforts.

PMID- 30198920
TI  - Radiation Safety Perceptions and Practices Among Pediatric Anesthesiologists: A
      Survey of the Physician Membership of the Society for Pediatric Anesthesia.
AB  - BACKGROUND: Pediatric anesthesiologists are exposed to ionizing radiation from x
      rays on an almost daily basis. Our goal was to determine the culture of safety in
      which they work and how they adhere to preventative strategies that minimize
      exposure risk in their daily practice. METHODS: After Institutional Review Board
      waiver and approval of the Society for Pediatric Anesthesia's research and
      quality and safety committees, an electronic e-mail questionnaire was sent to the
      Society's physician, nontrainee members and consisted of questions specific to
      provider use of protective lead shielding, the routine use of dosimeters, and
      demographic information. Univariate analyses were performed using the Wilcoxon
      rank sum test for ordinal variables, the Fisher exact test for categorical
      variables, and the Spearman test to analyze correlation between 2 ordinal
      variables, while a proportional odds logistic regression was used for a
      multivariable ordinal outcome analysis. P values of <.05 were considered
      statistically significant. RESULTS: Twenty-one percent (674/3151) of the surveyed
      anesthesiologists completed the online questionnaire. Radiation exposure is
      ubiquitous (98.7%), and regardless of sex, most respondents were either concerned
      or very concerned about radiation exposure (76.8%); however, women were
      significantly more concerned than men (proportional odds ratio, 1.66 [95%
      confidence interval, 1.20-2.31]; P = .002). Despite this and independent of sex,
      level of concern was not associated with use of a radiation dosimeter (P = .85),
      lead glasses (odds ratio, 1.07 [95% confidence interval, 0.52-2.39]; P = 1.0), or
      a thyroid shield (P = .12). Dosimeters were rarely (13%) or never used (52%) and
      were mandated in only 28.5% of institutions. Virtually none of the respondents
      had ever taken a radiation safety course, received a personal radiation dose
      report, notification of their radiation exposure, or knew how many millirem/y was
      considered safe. Half of the respondents were female, and while pregnant, 73%
      (151/206) tried to avoid radiation exposure by requesting not to be assigned to
      cases requiring x-rays. These requests were honored 78% (160/206) of the time.
      DISCUSSION: Despite universal exposure to ionizing radiation from x-rays,
      pediatric anesthesiologists do not routinely adhere to strategies designed to
      limit the intensity of this exposure and rarely work in institutions in which a
      culture of radiation safety exists. Our study highlights the need to improve
      radiation safety education, the need to change the safety culture within the
      operating rooms and imaging suites, and the need to more fully investigate the
      utility of dosimeters, lead shielding, and eye safety measures in pediatric
      anesthesia practice.

PMID- 30198921
TI  - Obstructive Sleep Apnea and Risk of Postcardiac Surgery Atrial Fibrillation.

PMID- 30198922
TI  - In Response.

PMID- 30198923
TI  - Perioperative Considerations for Evolving Artificial Pancreas Devices.
AB  - Type 1 diabetes mellitus is a lifelong condition. It requires intensive patient
      involvement including frequent glucose measurements and subcutaneous insulin
      dosing to provide optimal glycemic control to decrease short- and long-term
      complications of diabetes mellitus without causing hypoglycemia. Variations in
      insulin pharmacokinetics and responsiveness over time in addition to illness,
      stress, and a myriad of other factors make ideal glucose control a challenge.
      Control-to-range and control-to-target artificial pancreas devices (closed-loop
      artificial pancreas devices [C-APDs]) consist of a continuous glucose monitor,
      response algorithm, and insulin delivery device that work together to automate
      much of the glycemic management for an individual while continually adjusting
      insulin dosing toward a glycemic target. In this way, a C-APD can improve
      glycemic control and decrease the rate of hypoglycemia. The MiniMed 670G
      (Medtronic, Fridley, MN) system is currently the only Food and Drug
      Administration-cleared C-APD in the United States. In this system, insulin
      delivery is continually adjusted to a glucose concentration, and the patient
      inputs meal-time information to modify insulin delivery as needed. Data thus far
      suggest improved glycemic control and decreased hypoglycemic events using the
      system, with decreased need for patient self-management. Thus, the anticipated
      use of these devices is likely to increase dramatically over time. There are
      limited case reports of safe intraoperative use of C-APDs, but the Food and Drug
      Administration has not cleared any device for such use. Nonetheless, C-APDs may
      offer an opportunity to improve patient safety and outcomes through enhanced
      intraoperative glycemic control. Anesthesiologists should become familiar with C
      APD technology to help develop safe and effective protocols for their
      intraoperative use. We provide an overview of C-APDs and propose an introductory
      strategy for intraoperative study of these devices.

PMID- 30198924
TI  - Evaluation of the Determinants of Satisfaction With Postoperative Pain Control
      After Thoracoscopic Surgery: A Single-Center, Survey-Based Study.
AB  - BACKGROUND: The need to measure, compare, and improve the quality of pain
      management is important to patients, payers, and health care providers. Pain
      after thoracic surgery can be severe, and thoracoscopic approaches have not had
      the favorable impact on pain as anticipated. The aim of this study was to
      evaluate the determinants of patient satisfaction with acute pain management and
      the effectiveness of pain control after video-assisted thoracoscopic surgery
      using a modified version of the Revised American Pain Society Patient Outcome
      Questionnaire. METHODS: We performed a single-center, prospective, survey-based
      study of 300 patients who had undergone elective video-assisted thoracoscopic
      surgery. Patients were enrolled and completed the survey on postoperative day 1
      or 2. The primary outcome variable was patient-reported satisfaction with acute
      postoperative pain treatment measured on a 1-4 scale. The relationship between
      the items on the survey and patient satisfaction was analyzed to determine the
      factors significantly associated with satisfaction. RESULTS: Fifty-one percent of
      the patients had the highest satisfaction level with pain treatment, and 4% of
      the patients had the lowest satisfaction level. The mean reported acceptable pain
      level was 3.8 +/- 1.9 (numeric rating scale [NRS], 0-10). The average pain
      intensity score at the time of the survey was 2.8 +/- 2.1 (NRS, 0-10). The median
      for the most pain in the prior 24 hours was 7 (NRS, 0-10; interquartile range, 5
      9). Five items from the survey were significantly associated with the
      satisfaction level. The predictor with the highest associated odds ratio (OR)
      with satisfaction was the ability to participate in pain management decisions
      (OR, 1.45; P < .0001). Another positively associated predictor was receiving
      helpful information about pain treatment options (OR, 1.31; P = .002). Negatively
      associated predictors of patient satisfaction included level of pain intensity at
      time of survey (OR, 0.76; P = .002), lowest pain score in the prior 24 hours (OR,
      0.70; P = .0006), and having pain interfere with sleep in the postoperative
      period (OR, 0.72; P = .037). CONCLUSIONS: Our findings highlight several factors
      associated with patient satisfaction with acute postoperative pain management.
      Interventions focused on achieving acceptable pain levels for the majority of the
      time, ensuring that patients are able to get sleep, providing patients with
      helpful information about their pain treatment, and, most importantly, allowing
      patients to participate in decisions about their pain management may improve
      patient satisfaction with postoperative pain management.

PMID- 30198925
TI  - Elevated Presepsin Is Associated With Perioperative Major Adverse Cardiovascular
      and Cerebrovascular Complications in Elevated-Risk Patients Undergoing Noncardiac
      Surgery: The Leukocytes and Cardiovascular Perioperative Events Study.
AB  - BACKGROUND: Perioperative major adverse cardiovascular and cerebrovascular events
      (MACCEs) are incompletely understood, and risk prediction is imprecise.
      Atherogenic leukocytes are crucial in cardiovascular events. However, it is
      unclear if surgical interventions affect leukocyte counts or activation status.
      Therefore, we investigated whether noncardiac surgery in patients with elevated
      cardiovascular risk is associated with changes in atherogenic leukocyte subsets
      and if these changes are related to perioperative MACCEs. METHODS: We enrolled 40
      patients in this single-center prospective observational cohort study. Total
      leukocytes and subpopulations, including classical, intermediate, and
      nonclassical monocytes and natural killer and regulatory T cells, were quantified
      before surgery, at 2 and 6 hours after skin incision, and at postoperative days 1
      and 2 (POD1+2). The monocyte activation marker presepsin (sCD14-ST) was measured
      post hoc to determine differentiation of classical to nonclassical monocytes. We
      evaluated presepsin for prediction of the composite primary end point MACCE
      (cardiovascular death, myocardial infarction, myocardial ischemia, and stroke) at
      30 days. Its additive value to risk assessment based on high-sensitive cardiac
      troponin T and N-terminal probrain natriuretic peptide (NT-proBNP) was analyzed.
      RESULTS: We evaluated 38 patients, of whom 5 (13%) reached MACCE. In the entire
      cohort, classical monocytes continuously increased and peaked at POD1 (0.35 [0.23
      0.43] cells per nanoliter blood [nL] vs 0.45 [0.31-0.66] cells.nL, preoperative
      [pre-OP] vs POD1, P = .002). Intermediate monocytes doubled by POD1 (0.017 [0.013
      0.021] vs 0.036 [0.022-0.043] cells.nL, pre-OP versus POD1, P = .0003).
      Nonclassical monocytes decreased (0.022 [0.012-0.032] vs 0.012 [0.005-0.023]
      cells.nL, pre-OP vs 6 hours, P = .003). In our patient population, we did not
      detect changes in any of the other predefined leukocyte subsets investigated. In
      patients experiencing a MACCE, classical monocyte expansion was reduced (0.081 [
      0.16 to 0.081] cells.nL vs 0.179 [0.081 to 0.292] cells.nL, MACCE versus non
      MACCE, P = .016). Patients in the event group presented with elevated pre-OP
      presepsin (1528 [406-1897] pg.mL vs 123 [82.2-174] pg.mL, MACCE versus non-MACCE,
      P = .0001). Presepsin was associated with MACCE (area under the curve = 0.964,
      [0.846-0.998], P = .001). Presepsin above the calculated threshold >184 pg.mL was
      superior to high-sensitive cardiac troponin T for improvement of NT-proBNP-based
      risk prediction (28 [74%] vs 22 [58%] correctly classified patients, P = .014).
      CONCLUSIONS: Noncardiac surgery was associated with an increase in atherogenic
      leukocyte subsets. In a post hoc analysis, elevated pre-OP presepsin was
      associated with MACCE and improved NT-proBNP-based risk assessment. After
      validation in an independent data set, a presepsin cutoff of 184 pg.mL might
      qualify to complement NT-proBNP-based risk prediction, thereby increasing the
      proportion of correctly identified high-risk patients.

PMID- 30198926
TI  - National Trends and Factors Associated With Inpatient Mortality in Adult Patients
      With Opioid Overdose.
AB  - BACKGROUND: The prevalence of opioid misuse and opioid-related mortality has
      increased dramatically over the past decade. There is limited evidence on factors
      associated with mortality from opioid overdose in the inpatient setting. The
      primary objective was to report national trends in opioid overdose and mortality.
      The secondary objectives were to explore factors associated with inpatient
      mortality and report differences in prescription opioid overdose (POD) versus
      illicit opioid overdose (IOD) cohorts. METHODS: Using the 2010-2014 Nationwide
      Inpatient Sample, we performed a cross-sectional analysis and identified a
      weighted estimate of 570,987 adult patients with an International Classification
      of Disease, Ninth Revision, or External Cause of Injury code of POD or IOD. We
      performed multivariable logistic regression to identify predictors of inpatient
      mortality. The odds ratio (OR) and their associated 95% confidence interval (CI)
      are reported. RESULTS: Of the 570,987 patients with opioid overdose, 13.8% had an
      admissions diagnosis of IOD, and the remaining had POD. Among all opioid overdose
      admissions, the adjusted odds of IOD admissions increased by 31% per year (OR,
      1.31; 95% CI, 1.29-1.31; P < .001); however, the adjusted odds POD admissions
      decreased by 24% per year (OR, 0.76; 95% CI, 0.75-0.77; P < .001). The mortality
      was 4.7% and 2.3% among IOD and POD admissions, respectively. The odds of
      inpatient mortality increased by 8% per year among IOD admissions (OR, 1.08; 95%
      CI, 1.02-1.14; P < .007). The odds of inpatient mortality increased by 6% per
      year among all POD admissions (OR, 1.06; 95% CI, 1.03-1.09; P < .001). Those with
      IOD compared to POD had higher odds of mortality (OR, 2.03; 95% CI, 1.79-2.29; P
      < .001). Patients with age >=80 years of age and those with a diagnosis of a
      solid tumor malignancy had higher odds of mortality. Odds of inpatient mortality
      were decreased in African American versus Caucasian patients and in patients
      undergoing alcohol rehabilitation therapy. CONCLUSIONS: The increase in mortality
      provides a strong basis for further risk reduction strategies and intervention
      program implementation. Medical management of not only the opioid overdose but
      also the comorbidities calls for a multidisciplinary approach that involves
      policy makers and health care teams.

PMID- 30198927
TI  - Nighttime Extubation Does Not Increase Risk of Reintubation, Length of Stay, or
      Mortality: Experience of a Large, Urban, Teaching Hospital.
AB  - BACKGROUND: In the intensive care unit (ICU), extubation failure has been
      associated with greater resource utilization and worsened clinical outcomes. Most
      recently, nighttime extubation (NTE) has been reported as a risk factor for
      increased ICU and hospital mortality. We hypothesized that, in a large, urban,
      university-affiliated hospital with multidisciplinary assessment for extubation,
      rigorously protocolized extubation algorithms, and expert airway managers
      available at all times of day for assessment of high-risk extubations, NTE would
      not confer additional risk of adverse clinical outcomes. METHODS: This was a
      retrospective cohort study of mechanically ventilated adults at a single
      university-affiliated hospital. NTE was defined as occurring between 7:00 PM and
      6:59 AM the following day. All data were extracted from the institution's
      electronic medical record. Multi-vari-able regression analyses were used to
      assess associations between NTE and reintubation, ICU and hospital length of stay
      (LOS), and mortality with adjustments for demographic and clinical covariates
      defined a priori. Palliative, unplanned, and routine postoperative extubations
      were excluded in sensitivity analyses. RESULTS: Of 2241 patients, 204 of 2241
      (9.1%) underwent NTE. The rates of reintubation (NTE 6.9% versus daytime
      extubation [DTE] 12.4%; adjusted odds ratio [95% confidence interval {CI}], 0.78
      [0.43-1.41]; P = .41) and in-hospital mortality (NTE 3.4% versus DTE 5.9%;
      adjusted odds ratio [95% CI], 0.72 [0.28-1.84]; P = .49) were not found to
      differ. NTE, compared to DTE, was associated with shorter duration of mechanical
      ventilation (median [interquartile range], 1 [0-1] days vs 2 [1-4] days; adjusted
      ratio of geometric means [RGMs] [95% CI], 0.64 [0.54-0.70]; P < .001), ICU (2 [1
      5] days vs 4 [2-10] days; adjusted RGMs [95% CI], 0.65 [0.57-0.75]; P < .001),
      and hospital LOS (6 [3-18] days vs 13 [6-25] days; adjusted RGMs [95% CI], 0.64
      [0.56-0.74]; P < .001). These results were unchanged in sensitivity analyses.
      CONCLUSIONS: Patients who underwent NTE were not at increased risk of
      reintubation or in-hospital mortality. In addition, NTE was associated with a
      shortened duration of mechanical ventilation and hospital LOS. In health care
      systems with similar critical care delivery models, NTE may coincide with reduced
      resource utilization in appropriately selected patients.

PMID- 30198928
TI  - A Study of Practice Behavior for Endotracheal Intubation Site for Children With
      Congenital Heart Disease Undergoing Surgery: Impact of Endotracheal Intubation
      Site on Perioperative Outcomes-An Analysis of the Society of Thoracic Surgeons
      Congenital Cardiac Anesthesia Society Database.
AB  - BACKGROUND: In adults undergoing cardiopulmonary bypass surgery, oral intubation
      is typically preferred over nasal intubation due to reduced risk of sinusitis and
      infection. In children, nasal intubation is more common and sometimes preferred
      due to perceived benefits of less postoperative sedation and a lower risk for
      accidental extubation. This study sought to describe the practice of nasal
      intubation in the pediatric population undergoing cardiopulmonary bypass surgery
      and assess the risks/benefits of a nasal route against an oral one. METHODS:
      Patients <18 years of age in the Society of Thoracic Surgeons Congenital Heart
      Surgery Database between January 2010 and December 2015 were included. Patients
      with a preoperative endotracheal tube, tracheostomy, or known airway anomalies
      were excluded. Multivariable modeling was used to assess the association between
      route of tracheal intubation and a composite measure of infection risk (wound
      infection, mediastinitis, septicemia, pneumonia, and endocarditis). Covariates
      were included to adjust for important patient characteristics (eg, weight, age,
      comorbidities), case complexity, and center effects. Secondary outcomes included
      length of intubation, hospital length of stay, and airway complications including
      accidental extubations. We also performed a subanalysis in children <12 months of
      age in high-volume centers (>100 cases/y) examining how infection risk may change
      with age at the time of surgery. RESULTS: Nasal intubation was used in 41% of
      operations in neonates, 38% in infants, 15% in school-aged children, and 2% in
      adolescents. Nasal intubation appeared protective for accidental extubation only
      in neonates (P = .02). Multivariable analysis in infants and neonates showed that
      the nasal route of intubation was not associated with the infection composite
      (relative risk [RR], 0.84; 95% CI, 0.59-1.18) or a shorter length of stay (RR,
      0.992; 95% CI, 0.947-1.039), but was associated with a shorter intubation length
      (RR, 0.929; 95% CI, 0.869-0.992). Restricting to high-volume centers showed a
      significant interaction between age and intubation route with a risk change for
      infection occurring between approximately 6-12 months of age (P = .003).
      CONCLUSIONS: While older children undergoing nasal intubation trend similar to
      the adult population with an increased risk of infection, nasal intubation in
      neonates and infants does not appear to carry a similar risk. Nasal intubation in
      neonates and infants may also be associated with a shorter intubation length but
      not a shorter length of stay. Prospective studies are required to better
      understand these complex associations.

PMID- 30198929
TI  - Pharmacokinetics of Dexmedetomidine in Infants and Children After Orthotopic
      Liver Transplantation.
AB  - BACKGROUND: Dexmedetomidine (DEX) is a sedative and analgesic medication that is
      frequently used postoperatively in children after liver transplantation. Hepatic
      dysfunction, including alterations in drug clearance, is common immediately after
      liver transplantation. However, the pharmacokinetics (PK) of DEX in this
      population is unknown. The objective of this study was to determine the PK
      profile of DEX in children after liver transplantation. METHODS: This was a
      single-center, open-label PK study of DEX administered as an intravenous loading
      dose of 0.5 MUg/kg followed by a continuous infusion of 0.5 MUg/kg/h. Twenty
      subjects, 1 month to 18 years of age, who were admitted to the pediatric
      intensive care unit after liver transplantation were enrolled. Whole blood was
      collected and analyzed for DEX concentration using a dried blood spot method.
      Nonlinear mixed-effects modeling was used to characterize the population PK of
      DEX. RESULTS: DEX PK was best described by a 2-compartment model with first-order
      elimination. A typical child after liver transplantation with an international
      normalized ratio (INR) of 1.8 was found to have a whole blood DEX clearance of 52
      L/h (95% confidence interval [CI], 31-73 L/h). In addition, intercompartmental
      clearance was 246 L/h (95% CI, 139-391 L/h), central volume of distribution was
      186 L/70 kg (95% CI, 140-301 L/70 kg), and peripheral volume of distribution was
      203 L (95% CI, 123-338 L). Interindividual variability ranged from 11% to 111%
      for all parameters. Clearance was not found to be associated with weight but was
      found to be inversely proportional to INR. An increase in INR to 3.2 resulted in
      a 50% decrease in DEX clearance. Weight was linearly correlated with central
      volume of distribution. All other covariates, including age, ischemic time, total
      bilirubin, and alanine aminotransferase, were not found to be significant
      predictors of DEX disposition. CONCLUSIONS: Children who received DEX after liver
      transplantation have large variability in clearance, which was not found to be
      associated with weight but is influenced by underlying liver function, as
      reflected by INR. In this population, titration of DEX dosing to clinical effect
      may be important because weight-based dosing is poorly associated with blood
      concentrations. More attention to quality of DEX sedation may be warranted when
      INR values are changing.

PMID- 30198930
TI  - An In Vitro Model for Identifying Cardiac Side Effects of Anesthetics.
AB  - The understanding of anesthetic side effects on the heart has been hindered by
      the lack of sophisticated clinical models. Using micropatterned human-induced
      pluripotent stem cell-derived cardiomyocytes, we obtained cardiac muscle
      depressant profiles for propofol, etomidate, and our newly identified anesthetic
      compound KSEB01-S2. Propofol was the strongest depressant among the 3 compounds
      tested, exhibiting the largest decrease in contraction velocity, depression rate,
      and beating frequency. Interestingly, KSEB01-S2 behaved similarly to etomidate,
      suggesting a better cardiac safety profile. Our results provide a proof-of
      concept for using human-induced pluripotent stem cell-derived cardiomyocytes as
      an in vitro platform for future drug design.

PMID- 30198931
TI  - Transversus Abdominal Plane Block in Children: Efficacy and Safety: A Randomized
      Clinical Study and Pharmacokinetic Profile.
AB  - BACKGROUND: The transversus abdominis plane (TAP) block has become a common
      regional anesthesia technique for pain management in a wide variety of abdominal
      procedures. Evidence to support any particular local anesthetic regimen as well
      as pharmacokinetic and systemic toxicity risks of TAP block remain insufficiently
      studied in children. The aim of this study was to compare the analgesic effects
      and investigate pharmacokinetic profile of levobupivacaine after ultrasound
      guided TAP block using a low volume/high concentration (LVHC) or a high
      volume/low concentration (HVLC) solution in children. METHODS: This prospective
      randomized study included children scheduled for day-case inguinal surgery.
      Children were randomized to receive TAP block using 0.4 mg.kg levobupivacaine as
      either HVLC (0.2 mL.kg of 0.2% levobupivacaine) or LVHC (0.1 mL.kg of 0.4%
      levobupivacaine). The primary outcome was the number of children who required
      opioid rescue analgesia postoperatively. Pharmacokinetic profile study of
      levobupivacaine was also performed. RESULTS: Seventy patients were equally
      randomized, and 65 were included in the final analysis. Seventy-one percent of
      patients did not require any postoperative opioid analgesia. The number of
      patients who received rescue analgesia was 12 (35%) in the LVHC group and 7 (23%)
      in the HVLC group (relative risk, 0.64; 95% confidence interval [CI], 0.29-1.42;
      P = .26). Mean pain scores (FLACC [faces, legs, activity, cry, and
      consolability]) at postanesthesia care unit discharge did not differ between LVHC
      and HVLC groups, respectively, 0.39 +/- 0.86 and 1 +/- 1.71 with mean group
      difference -0.60 (95% CI, -1.27 to 0.06; P = .08). The pharmacokinetic profile of
      levobupivacaine was comparable in the 2 groups: the mean total and free
      levobupivacaine peak concentrations were 379 +/- 248 and 3.95 +/- 3.16 ng.mL,
      respectively, occurring 22.5 +/- 11 minutes after injection. The highest total
      and free levobupivacaine concentrations collected, respectively, 1360 and 15.1
      ng.mL, remained far below theoretical toxic thresholds. CONCLUSIONS: In children,
      quality of postoperative pain control provided by TAP block using levobupivacaine
      0.4 mg.kg administered as either HVLC or LVHC did not differ and was associated
      with a very low risk of local anesthetic systemic toxicity.

PMID- 30198932
TI  - Role of Endocannabinoid System in the Peripheral Antinociceptive Action of
      Aripiprazole.
AB  - BACKGROUND: Recently, we demonstrated that the antipsychotic dopaminergic and
      serotoninergic agonist aripiprazole induced peripheral antinociception. However,
      the mechanism underlying this effect has not been fully established. Here, our
      aim was to identify possible relationships between this action of aripiprazole
      and the endocannabinoid system. METHODS: All drugs were given locally into the
      right hind paw of male Swiss mice weighing 30-35 g in a volume of 20 uL. The
      hyperalgesia was induced by intraplantar injection of prostaglandin E2 (2 MUg).
      Aripiprazole was injected 10 minutes before the measurement, and an irreversible
      inhibitor of anandamide hydrolase (MAFP), an inhibitor for monoacylglycerol
      lipase (JZL184), and an anandamide reuptake inhibitor (VDM11) were given 10
      minutes before the aripiprazole. Nociceptive thresholds were measured using an
      algesimetric apparatus in the third hour after prostaglandin E2 injection. Data
      were analyzed by ANOVA and Bonferroni tests. RESULTS: The antinociceptive effect
      induced by aripiprazole (100 MUg) was blocked by cannabinoid 1 or 2 receptor
      antagonists AM251 (40 MUg [P < .01], 80 MUg [P < .0001], and 160 MUg [P < .0001])
      and AM630 (100 MUg [P < .0001], 200 MUg [P < .0001], and 400 MUg [P < .0001]),
      respectively. The peripheral antinociception induced by aripiprazole (25 MUg) was
      enhanced by administration of the inhibitor of fatty acid amide hydrolase (MAFP,
      0.5 MUg [P < .0001]) or monoacylglycerol lipase (JZL184, 4 MUg [P < .0001]).
      Moreover, a similar enhancement was observed with the anandamide reuptake
      inhibitor (VDM11, 2.5 MUg [P < .0001]). CONCLUSIONS: These results provide
      evidence for the involvement of the endocannabinoid system in peripheral
      antinociception induced by aripiprazole treatment.

PMID- 30198933
TI  - What Is New in Obstetric Anesthesia: The 2017 Gerard W. Ostheimer Lecture.
AB  - The Gerard W. Ostheimer lecture is given each year at the Society for Obstetric
      Anesthesia and Perinatology annual meeting and is intended to summarize important
      new scientific literature relevant to practicing obstetric anesthesiologists.
      This review highlights some of the most consequential papers covered in this
      lecture. It discusses landmark clinical trials that are likely to change the
      practice of obstetrics and obstetric anesthesia. It summarizes several articles
      that focus on how to optimize the provision of neuraxial anesthesia and
      postoperative pain control. Finally, it reviews studies aimed at identifying
      systems-based interventions that can improve obstetrical outcomes. A proposed "to
      do" list focused on quality improvement initiatives that can be implemented on
      labor and delivery units is provided.

PMID- 30198935
TI  - Nitrous Oxide Supply Systems.

PMID- 30198934
TI  - Pupillary Pain Index Changes After a Standardized Bolus of Alfentanil Under
      Sevoflurane Anesthesia: First Evaluation of a New Pupillometric Index to Assess
      the Level of Analgesia During General Anesthesia.
AB  - BACKGROUND: The pupillary pain index (PPI) is a novel pupillometric index,
      designed to assess intraoperative analgesia. It is based on the evaluation of the
      pupillary response to electrical stimuli of increasing intensity. It ranges from
      1 (low level of pupillary reactivity, high level of analgesia) to 10 (high level
      of pupillary reactivity, low level of analgesia). In this first evaluation of the
      PPI, our objective was to investigate the PPI changes after a bolus of 10 ug.kg
      of alfentanil in children under sevoflurane general anesthesia. METHODS: After
      ethics committee approval and informed consent, 20 healthy children (9 +/- 5
      years) undergoing elective surgery under general anesthesia were included in this
      prospective, open, registered pilot study (NCT02646592). Anesthetic induction was
      standardized with sevoflurane 6% and propofol 1 mg.kg. After tracheal intubation,
      sevoflurane concentration was maintained at 2% for 10 minutes. A first PPI
      measurement was performed (PPI-1), and a bolus of 10 ug.kg was administered. Two
      minutes after this bolus, a second PPI measurement was performed (PPI-2). Heart
      rate, blood pressure, and bispectral index were recorded before and after each
      PPI measurement. Resting pupillary diameter was recorded before each PPI
      measurement. PPI scores before and after the bolus of alfentanil were compared
      using a Wilcoxon signed rank test. RESULTS: PPI scores decreased after
      administration of a bolus of alfentanil (median difference: -3 [95% confidence
      interval, -4 to -2]). The median (quartiles) of PPI-1 (baseline, before
      alfentanil) was 6 (4, 7), and the median (quartiles) of PPI-2 (after alfentanil)
      was 2 (2, 3) (P < .001). No difference was found in resting pupillary diameter
      before PPI-1 and PPI-2 (2.2 +/- 0.2 and 2.2 +/- 0.3 mm, respectively; P = .86).
      There were no significant changes in heart rate or blood pressure after PPI
      measurements (P = .46 and .49, respectively). Bispectral index was slightly
      increased after PPI measurements (P = .01; mean bispectral index increase <5%).
      No withdrawal movements occurred during PPI measurements. CONCLUSIONS: There was
      a significant decrease in PPI after alfentanil administration. The results of
      this pilot study suggest that PPI score decreases when the level of analgesia
      increases. PPI measurement was not associated with a clinical or hemodynamic
      nociceptive response. This new index might provide useful information to
      individually adapt opioid administration before nociceptive stimuli under general
      anesthesia.

PMID- 30198936
TI  - A Systematic Comparison of Designs to Study Human Fecundity.
AB  - BACKGROUND: Several epidemiologic designs allow studying fecundability, the
      monthly probability of pregnancy occurrence in noncontracepting couples in the
      general population. These designs may, to varying extents, suffer from
      attenuation bias and other biases. We aimed to compare the main designs: incident
      and prevalent cohorts, pregnancy-based, and current duration approaches. METHODS:
      A realistic simulation model produced individual reproductive lives of a
      fictitious population. We drew random population samples according to each study
      design, from which the cumulative probability of pregnancy was estimated. We
      compared the abilities of the designs to highlight the impact of an environmental
      factor influencing fecundability, relying on the Cox model with censoring after
      12 or 6 months. RESULTS: Regarding the estimation of the cumulative probability
      of pregnancy, the pregnancy-based approach was the most prone to bias. When we
      considered a hypothetical factor associated with a hazard ratio (HR) of pregnancy
      of 0.7, the estimated HR was in the 0.78-0.85 range, according to designs. This
      attenuation bias was largest for the prevalent cohort and smallest for the
      current duration approach, which had the largest variance. The bias could be
      limited in all designs by censoring durations at 6 months. CONCLUSION:
      Attenuation bias in HRs cannot be ignored in fecundability studies. Focusing on
      the effect of exposures during the first 6 months of unprotected intercourse
      through censoring removes part of this bias. For risk factors that can accurately
      be assessed retrospectively, retrospective fecundity designs, although biased,
      are not much more strongly so than logistically more intensive designs entailing
      follow-up.

PMID- 30198938
TI  - Crowdfunding Platforms for Nursing Research.

PMID- 30198939
TI  - Use of Clinical Faculty Input in Development of an Error and Near-Miss Reporting
      Form.
AB  - BACKGROUND: Nonreporting of medical errors is an impediment to error prevention
      and safety in the clinical environment. Many prelicensure nursing education
      programs do not have policies, procedures, or forms to support student reporting
      of errors or near misses during their clinical experiences. PURPOSE: The purpose
      of this study was to describe the experiences of clinical faculty with
      prelicensure nursing student errors or near misses in the clinical environment
      and to use this information to create a reporting form. METHODS: Focus groups
      were used to obtain information about the experiences of clinical faculty (n =
      28) with errors or near misses of students. RESULTS: Clinical faculty reported
      students having safety issues with medication administration, being too task
      oriented, and modeling shortcut behaviors they had witnessed in clinical practice
      rather than performing skills as they had learned them. Using information
      obtained, a clinical error and near-miss reporting form was developed.
      CONCLUSIONS: This form has the potential to increase patient safety in the
      clinical environment by improving reporting.

PMID- 30198937
TI  - Metallic Air Pollutants and Breast Cancer Risk in a Nationwide Cohort Study.
AB  - BACKGROUND: Toxic metals show evidence of carcinogenic and estrogenic properties.
      However, little is known about the relationship between airborne metals and
      breast cancer. We evaluated the risk of breast cancer in relation to exposure to
      toxic metallic substances in air, individually and combined, in a US-wide cohort.
      METHODS: Sister Study participants (n = 50,884), breast cancer-free women who had
      a sister with breast cancer were recruited, from 2003 to 2009. The 2005
      Environmental Protection Agency National Air Toxic Assessment's census-tract
      estimates of metal concentrations in air (antimony, arsenic, cadmium, chromium,
      cobalt, lead, manganese, mercury, nickel, and selenium) were matched to
      participants' enrollment residence. We used Cox regression to estimate the
      association between quintiles of individual metals and breast cancer incidence
      and weighted quantile sum regression to model the association between the metal
      mixture and breast cancer. RESULTS: A total of 2,587 breast cancer cases were
      diagnosed during follow-up (mean = 7.4 years). In individual chemical analyses
      comparing the highest to lowest quintiles, postmenopausal breast cancer risk was
      elevated for mercury (hazard ratio [HR] = 1.3, 95% confidence interval [CI], 1.1,
      1.5), cadmium (HR = 1.1, 95% CI, 0.96, 1.3), and lead (HR = 1.1, 95% CI, 0.98,
      1.3). The weighted quantile sum index was associated with postmenopausal breast
      cancer (odds ratio [OR] = 1.1, 95% CI, 1.0, 1.1). Consistent with the individual
      chemical analysis, the most highly weighted chemicals for predicting
      postmenopausal breast cancer risk were lead, cadmium, and mercury. Results were
      attenuated for overall breast cancer. CONCLUSIONS: Higher levels of some airborne
      metals, specifically mercury, cadmium, and lead, were associated with a higher
      risk of postmenopausal breast cancer.

PMID- 30198941
TI  - Prevalence of Hearing Loss Among Noise-Exposed Workers Within the Health Care and
      Social Assistance Sector, 2003 to 2012: Erratum.

PMID- 30198940
TI  - Nursing Students' Transfer of Learning During a Disaster Tabletop Exercise.
AB  - BACKGROUND: Disasters require nurses to make decisions. A tabletop exercise, used
      in disaster education, is a classroom activity for solving problems. PURPOSE: The
      study purposes were to (1) describe, as scores, the transfer of learning from
      basic medical-surgical coursework to student decisions made during a disaster
      scenario tabletop exercise and (2) identify students' attitudes about their use
      of their previous learning during this experience. METHOD: Researcher-designed
      instruments and a tabletop exercise were used to measure prelicensure students'
      transfer of select basic medical-surgical learning to their decisions during the
      exercise. RESULTS: Mean (SD) student scores during the tabletop exercise were as
      follows-Tabletop Matrix: infection, 17.61 (6.03); bleeding, 14.93 (5.36); pain,
      11.17 (5.08); electrolyte, 13.73 (6.19); disaster knowledge: 19.46 (3.08); and
      attitudes: 51.41 (5.43). CONCLUSION: During this tabletop exercise, students
      demonstrated transfer of learning.

PMID- 30198942
TI  - The Barcelona Principles: An Agreement on the Use of Human Donated Tissue for
      Ocular Transplantation, Research, and Future Technologies(c).
AB  - PREAMBLE: The Barcelona Principles: An Agreement on the use of human donated
      tissue for ocular transplantation, research, and future technologies (Agreement)
      is a global bioethical framework (GBF), developed by the eye bank and ophthalmic
      communities, to inform on the management of altruistic and voluntary donations;
      their subsequent utility within ophthalmology and research; their retention as a
      public resource for the shared benefit of all; and their accessibility by waiting
      recipients.The Agreement is the result of global sector engagement over a 12
      month period-led by the Global Alliance of Eye Bank Associations. Its aim is to
      provide leadership, guidance and recommendations that inform and support sound
      policy, and sector wide strategic planning and implementation at local, national,
      regional, and international levels.Inspired by the Declaration of Istanbul on
      Organ Trafficking and Transplant Tourism, this Agreement affirms the importance
      of the missions of the United Nations Sustainable Development Goals (Transforming
      our World: the 2030 Agenda for Sustainable Development); Universal Declaration of
      Human Rights; World Medical Association's Declaration of Helsinki-Ethical
      Principles for Medical Research Involving Human Subjects, and their Statement on
      Organ and Tissue Donation; The Council for International Organizations of Medical
      Science's International Ethical Guidelines for Health-related Research Involving
      Humans 2016; and accords with the World Health Organization's 2010 Guiding
      principles on human cell, tissue, and organ transplantation-WHA63.22.With
      millions waiting for a corneal transplant at any given moment-and the majority
      residing in lower resource locations, a significant component of this Agreement
      promotes equitable allocation systems for waiting recipients, and the development
      of self-sufficient services. It recognises important instruments, such as the
      International Council of Ophthalmology 2017 Position Statement: Donation,
      Processing, Allocation, Advocacy, and Legislation Supporting Human Corneal Tissue
      for Ocular Transplant; the World Health Organization's Universal Eye Health
      Global Action Plan 2014 to 2019, and the mission of the International Agency for
      the Prevention of Blindness.Future biological innovations/technologies are also
      addressed within the Agreement, promoting research and development that seek to
      improve donation utility, reduce burden, and improve therapeutic options for
      recipients, without ethical compromise.The Agreement has been developed by the
      Global Alliance of Eye Bank Associations in conjunction with the International
      Council of Ophthalmology, International Agency for the Prevention of Blindness,
      The Corneal Society, Asian Eye Bank Association, European Eye Bank Association,
      Eye Bank Association of America, Eye Bank Association of Australia and New
      Zealand, Eye Bank Association of India, the Pan American Association of Eye
      Banks, and in countries and regions without eye bank organizations, their
      ophthalmic societies-such as the Ophthalmological Society of the West Indies, and
      the Pacific Eye Care Society.Finally, we endorse the current international
      consensus that prohibits trafficking and transplant tourism.

PMID- 30198943
TI  - Improving Patient and Caregiver New Medication Education Using an Innovative
      Teach-back Toolkit.
AB  - BACKGROUND: Patients and caregivers are often not adequately informed about new
      medications. Nurses can lead innovations that improve new medication education.
      LOCAL PROBLEM: Healthcare Consumer Assessment of Healthcare Providers and Systems
      (HCAHPS) scores on medication questions trailed state and national levels in one
      Midwestern hospital. METHODS: This quality improvement project, guided by the
      Ottawa Model of Research Use and the Always Use Teach-back! innovative toolkit,
      used a 1-group pre- and posteducation design with RNs, patients, and caregivers.
      INTERVENTION: RNs (n = 25) were observed in patient/caregiver education and
      surveyed in confidence/con-viction in the teach-back method before and after
      education. Patients' (n = 74) and caregivers' (n = 33) knowledge was assessed.
      RESULTS: RNs reported significant increases in conviction in the importance of (P
      < .0001), confidence in using (P < .0001), and frequency in using (P < .0001)
      teach-back. With teach-back, both patients and caregivers recalled the purpose
      and side effects of new medications. Specific HCAHPS scores increased from 6% to
      10%. CONCLUSION: The teach-back method strengthened safe nursing practice and
      enhanced quality in new medication education.

PMID- 30198944
TI  - Mealtime Assistance ... From Chaos to Calm: A Collaborative Best Practice
      Implementation Project.
AB  - BACKGROUND: Providing appropriate and timely mealtime assistance to hospitalized
      patients should be part of a multifaceted and multidisciplinary approach to
      optimizing a patient's nutritional care plan. PROBLEM: There was anecdotal
      evidence at the study hospital that patients did not receive adequate and/or
      timely assistance at mealtimes. APPROACH: A best practice implementation project,
      using a proven strategy of audit, feedback, and reaudit, was used to effect
      practice change on an acute general medical ward. OUTCOMES: The combined
      interventions of staff engagement, redesigning the model of care to reprioritize
      activities at mealtimes, clarifying nutritional care roles and responsibilities,
      introducing a protected mealtime and a novel 2-tiered colored tray system, and
      implementing an awareness and education program have resulted in significant
      improvements in mealtime assistance. CONCLUSIONS: Success of the project is
      considered to be replicable and sustainable hospitalwide and more broadly.

PMID- 30198945
TI  - Developing an Intervention to Reduce Harm in Hospitalized Patients: Patients and
      Families in Research.
AB  - BACKGROUND: Patient safety-focused research may be strengthened by the inclusion
      of patients and family members in research design; yet, published methodologies
      for doing so are scarce. PURPOSE: This study engaged patients and families in
      research design of an intervention to increase patient/family engagement, with
      reduction of harm in hospitalized patients. METHODS: The study design team
      convened a Patient Safety Advisory Panel to explore potential testable
      interventions to increase patient/family engagement with safety. They explored
      the preferred intervention, Speak Up-My Advocate for Patient Safety (MAPS),
      through multistakeholder focus groups. RESULTS: Participants emphasized the
      importance of including patient/family when designing interventions. Regarding
      the Speak Up-MAPS intervention, perceptions from stakeholders were mixed,
      including the value and potential complexity, role confusion, and cost of the
      proposed advocate role. CONCLUSION: Intentional inclusion of the patient/family
      in research is important and practical. Both strengths and challenges of the
      proposed intervention were identified, indicating the need for further study.

PMID- 30198946
TI  - Fall Risk Program for Oncology Inpatients: Addition of the "Traffic Light" Fall
      Risk Assessment Tool.
AB  - BACKGROUND: The incidence of falls on inpatient oncology units indicated the need
      for quality improvement. This project aimed to reduce falls by implementing a
      fall reduction plan including the "Traffic Light" Fall Risk Assessment Tool (TL
      FRAT). LOCAL PROBLEM: We retrospectively reviewed the oncology unit fall data
      from January 2013 to September 2014 and found that the average fall incidence was
      high. METHODS: The project used a program evaluation design, and the process was
      guided by Kotter's 8-step change model. INTERVENTIONS: We implemented the TL-FRAT
      to classify oncology inpatients at a high risk of falling in advance. RESULTS:
      The average fall incidence and falls with injury during the project were reduced.
      CONCLUSIONS: Adding the TL-FRAT to the fall protocol on the units effectively
      reduced the incidence of falls related to impaired mobility. The TL-FRAT can
      improve nurses' sensitivity to falls related to impaired mobility and,
      subsequently, guide corresponding fall prevention strategies.

PMID- 30198947
TI  - Video Monitoring for Fall Prevention and Patient Safety: Process Evaluation and
      Improvement.
AB  - BACKGROUND: Although video monitoring has been shown to reduce falls among at
      risk hospitalized patients, there are no identified best practices for the
      monitoring process. PURPOSE: The purpose of this study was to evaluate the
      monitoring process at a large teaching hospital, with the goal of making
      improvements and standardizing monitoring practices. METHODS: Patients and
      nursing staff perceptions about the video monitoring process were elicited via
      survey, and perceptions of monitor technicians were obtained through structured
      interview. RESULTS: Video monitoring was perceived by all groups as effective in
      promoting patient safety. Nursing staff and monitor technicians also indicated
      that monitoring protects patient safety in other high-risk situations.
      Suggestions for improvement and standardization in the monitoring process were
      made by study participants. CONCLUSIONS: Suggested changes and standardization of
      the monitoring process have been implemented in the study facility. Insights are
      provided for other facilities considering video monitoring for patient safety.

PMID- 30198948
TI  - A Systematic Review of Criteria-Led Patient Discharge.
AB  - BACKGROUND: This article reports on a systematic review conducted to critique
      safety, quality, length of stay, and implementation factors regarding criteria
      led discharge. PURPOSE: Improving patient flow and timely bed capacity is a
      global issue. Criteria-led discharge enables accelerated patient discharge in
      accordance with patient selection. METHODS: A systematic review was conducted to
      identify literature on criteria-led discharge from 2007 to 2017. The quality of
      articles was appraised using a tool for disparate studies. Two reviewers
      extracted relevant data independently. RESULTS: Fifteen studies were identified
      that showed no increase in patient readmission or complication rates with
      criteria-led discharge, demonstrating patient safety. The quality of the patient
      discharge was unremarkable. None of the studies showed an increase in length of
      stay. CONCLUSIONS: The safety, quality, and length of stay for patients
      discharged through criteria-led discharge are inextricably linked to the process
      adopted for its implementation.

PMID- 30198949
TI  - Individualized Fall Prevention Program in an Acute Care Setting: An Evidence
      Based Practice Improvement.
AB  - BACKGROUND: A 245-bed community hospital established patient fall prevention as
      its patient safety priority. PROBLEM: The hospital's fall prevention program was
      not consistently effective. The baseline fall rate was 3.21, higher than the
      National Database of Nursing Quality Indicators' median of 2.91. APPROACH: An
      interprofessional fall prevention team evaluated the hospital's fall program
      using the evidence-based practice improvement model. A clinical practice
      guideline with 7 key practices guided the development of an individualized fall
      prevention program with interventions to address 4 fall risk categories and an
      algorithm to identify interventions. Interventions included nurse-driven mobility
      assessment, purposeful hourly rounding, and video monitoring for confused and
      impulsive fall-risk patients. OUTCOMES: The fall rate decreased to 1.14, with a
      72% expense reduction based on decreased sitter usage. CONCLUSIONS: An
      interprofessional team successfully reduced falls with an evidence-based fall
      prevention program.

PMID- 30198950
TI  - Sustaining Quality Improvement: Long-Term Reduction of Nonventilator Hospital
      Acquired Pneumonia.
AB  - BACKGROUND: Hospital-acquired pneumonia is now the number one hospital-acquired
      infection. Hospitals have addressed ventilator-associated pneumonia; however,
      patients not on a ventilator acquire more pneumonia with significant associated
      mortality rates. LOCAL PROBLEM: In our hospital, non-ventilator-associated
      pneumonia was occurring on all types of units. METHODS: The Influencer Model was
      used to reduce nonventilator hospital-acquired pneumonia rates. Statistical
      process control R and X-bar-charts were monitored monthly. INTERVENTIONS: After a
      gap analysis, an interdisciplinary team implemented enhanced oral care before
      surgery and on the units, changed tube management, and monitored stress ulcer
      medication. RESULTS: We achieved a statistically significantly reduction (P =
      .01) in pneumonia rates that have been sustained over 4 years. CONCLUSIONS:
      Sustaining change requires (a) a continued team-based, collaborative approach,
      (b) ongoing stakeholder and executive leadership engagement,

PMID- 30198951
TI  - Quiet Time Improves the Patient Experience.
AB  - BACKGROUND: A quiet environment promotes rest and healing but is often
      challenging to provide in a busy acute care setting. Improving quiet in the
      hospital for designated hours improves patient satisfaction. Such efforts have
      typically been the primary responsibility of the nursing staff. LOCAL PROBLEM:
      Two medical units with consistently low Hospital Consumer Assessment of Health
      Care Providers and Systems (HCAHPS) "always quiet" scores were chosen for this
      study. METHODS: A multidisciplinary team used Lean methods and the Model for
      Improvement to test interventions for quiet time (QT) and used HCAHPS "always
      quiet" scores as the primary outcome measure. INTERVENTIONS: The team instituted
      nighttime and afternoon QT supported by rounding and scripting, dimming lights,
      lowering staff voices, offering a sleep menu at night, and replacing noisy
      wheels. RESULTS: Quiet scores improved on both units after 11 months.
      CONCLUSIONS: Noise in hospitals is often beyond the scope of nurse-driven
      improvement; however, a QT protocol led by nurses, developed by multiple
      stakeholders, and focused on changing expectations for quiet can lead to
      measurable improvements in patient perception of quiet.

PMID- 30198952
TI  - Quality Improvement Project to Manage Workplace Violence in Hospitals: Lessons
      Learned.
AB  - BACKGROUND: The study of workplace violence has focused on quantifying the
      problem and profiling perpetrators and victims. Intervention studies are scarce.
      The diverse nature of violence risk in hospitals highlights the need for broad
      training in risk recognition and de-escalation. LOCAL PROBLEM: A violence
      management program was piloted on a general medical unit following staff requests
      for measures to protect them from patient and visitor violence. METHODS: An
      independent pre/posttest design measured changes in participant knowledge. The
      Staff Observation Assessment Scale Revised (SOAS-R) was used for data collection
      on aggression pre- and postimplementation. INTERVENTIONS: The violence management
      training program included in situ simulation training in de-escalation
      techniques. RESULTS: Knowledge of de-escalation techniques to reduce violence
      risk increased. Important lessons were learned for ongoing program
      implementation. CONCLUSIONS: Violence management programs can lead to more
      effective risk management. Instruments to collect data on aggression should be
      linked to mandatory incident reporting, and existing behavioral response teams
      should be involved in incident tracking.

PMID- 30198953
TI  - Impact of Nurse Peer Review on a Culture of Safety.
AB  - BACKGROUND: Nursing peer review (NPR) is essential in evaluating nursing
      practice. A common theme throughout the literature is that NPR holds nurses
      accountable for their practice. PROBLEM: The nursing profession has struggled to
      conduct peer review consistently due to lack of a standardized framework.
      APPROACH: A NPR program was developed, implemented, and evaluated in a 355-bed
      acute care hospital in the Midwestern United States. OUTCOMES: A pre- and
      postdesign using the Agency for Healthcare Research and Quality Hospital Survey
      on Patient Safety Culture was used for evaluation. Paired t test results revealed
      statistically significant differences in group means for 2 questions: mistakes
      have led to positive changes here (P < .001, d = 1.31), and staff will freely
      speak up (P = .002, d = 0.67). Clinically significant differences in group means
      were noted for the remaining survey items. CONCLUSIONS: Implementation of an NPR
      program is a promising means to improve the culture of safety in health care
      institutions.

PMID- 30198954
TI  - Using Lean Six Sigma to Improve Controlled Drug Processes and Release Nursing
      Time.
AB  - BACKGROUND: Hospital controlled drug processes are established to adhere to
      legislation, with little consideration of efficiency of processes. LOCAL PROBLEM:
      A controlled drug process existed, where nurses requested a porter to collect a
      hand-written order; however, only 19% of drug orders were processed this way.
      Instead, an unscheduled, ad hoc process led to an average of 17 nurse journeys to
      pharmacy daily. We aimed to reduce nurse journeys to the pharmacy by 25% to
      release nursing time. METHODS: A pre-/postintervention design was used with Lean
      Six Sigma methods. INTERVENTIONS: A multifaceted intervention involved process
      redesign, increasing the frequency of a porter-led delivery service, amending
      delivery times to reflect times of greatest need, and streamlining checking
      requirements. RESULTS: Following implementation, there was a statistically
      significant 44% decrease in nurse journeys to pharmacy for drug collections,
      which was maintained after 18 months. CONCLUSIONS: Interprofessional
      collaboration improving hospital-wide processes can have significant benefits for
      the release of nursing time.

PMID- 30198957
TI  - Factors Affecting the Adherence to Disease-Modifying Therapy in Patients With
      Multiple Sclerosis.

PMID- 30198956
TI  - It's Not Brain Surgery.

PMID- 30198955
TI  - Hemofiltration Successfully Eliminates Severe Cytokine Release Syndrome Following
      CD19 CAR-T-Cell Therapy.
AB  - Cytokine release syndrome (CRS) remains to be a major adverse effect of chimeric
      antigen receptor T (CAR-T) cell therapy in B-cell acute lymphoblastic leukemia (B
      ALL) and lymphoma. It was urgent to explore novel strategy for managing severe
      CRS. We conducted a clinical trial to assess the safety and efficacy of CD19
      targeting CAR-T-cells in the treatment of relapsed and chemotherapy-refractory B
      ALL and lymphoma. A 10-year-old boy with B-ALL who never achieved minimal
      residual disease (MRD) negative status after 5 courses of chemotherapy was
      enrolled into our study and received a total of 3.19*10/kg autologous CD19 CAR-T
      cells. Before CAR-T-cell infusion, naive lymphocytes made up 41.8% of bone marrow
      cells, which were reduced to 1% at the 14th day after transfusion, with MRD<10.
      However, this patient developed grade 4 CRS, multiple organ failure,
      hemophagocytic syndrome, neurotoxicity, and severe pulmonary infection after CAR
      T-cell therapy. Tocilizumab and glucocorticoids treatment were ineffective for
      controlling the adverse effects and in contrast, hemofiltration immediately
      ameliorated the severe CRS and prevented the exacerbation of multiple organ
      dysfunction, pneumonia, and hydrosarca caused by CAR-T-cell therapy. All side
      effects disappeared within days following hemofiltration. Hemofiltration helped
      quickly clear cytokines, speeded up patient recover, and successfully resolved
      the severe CRS crisis. This was the first report, reporting the successful use of
      hemofiltration to eliminate adverse reactions of CAR-T-cell therapy.

PMID- 30198959
TI  - Salivary Cortisol Profile Under Different Stressful Situations in Female College
      Students: Moderating Role of Anxiety and Sleep.

PMID- 30198958
TI  - Effect of Multiple Sclerosis on Dyadic Adjustment.
AB  - PURPOSE: This study examines the dyadic adjustment of married men and women with
      multiple sclerosis (MS). METHOD: This cross-sectional study consists of 40
      patients with MS who were married and being followed in the neurology clinic of a
      university hospital. Data collection was performed by face-to-face interviews
      with only the participant and the researcher present. The participants filled in
      the Expanded Disability Status Scale, a sociodemographic form, and a dyadic
      adjustment scale. RESULTS: The study group was 75% male, with age ranging from 27
      to 65 years (mean, 44.40 +/- 9.31 years). Expanded Disability Status Scale scores
      ranged from 0 to 7 (mean, 3.25 +/- 1.94); 95% of the subjects were having
      relapses and remissions. Scores for patients with MS who were not considering
      divorce were statistically significantly higher than patients with MS who were
      considering divorce for dyadic adjustment (z = 3.845, P = .000), common view (z =
      2.336, P = .020), endearment (z = 2.701, P = .007), and total scores (z = 3.399,
      P = .001). CONCLUSION: Most of the patients with MS who participated in this
      study were diagnosed with relapsing-remitting MS with a mean Expanded Disability
      Status Scale score of 3, indicating that patients had the physical ability to
      perform routine activities. The total dyadic adjustment scale score (107.7) is
      above average, indicating that dyadic adjustment was at a good level.

PMID- 30198960
TI  - Disialoganglioside GD2 Expression in Pediatric Rhabdomyosarcoma: A Case Series
      and Review of the Literature.
AB  - Rhabdomyosarcoma (RMS) is the most common pediatric soft tissue sarcoma. Despite
      aggressive therapy, patients with metastatic or relapsed disease experience
      dismal outcomes and novel therapies are urgently needed. In this study, we
      evaluated expression of disialoganglioside (GD2), a cell surface antigen with
      therapeutic implication, in 16 RMS patient samples. Scoring revealed GD2
      positivity in 25% of the samples. These data suggest that a small subset of RMS
      tumors express GD2, which may be a therapeutic target in these patients.

PMID- 30198961
TI  - Importance of Acute Lymphoblastic Leukemia-type Therapy for Bilineal Acute
      Leukemia.
AB  - We examined 3 pediatric patients with bilineal acute leukemia. Patient 1 with B
      cell acute lymphoblastic leukemia (ALL) and acute myelogenous leukemia (AML) with
      B-ALL dominance responded well to prednisolone and ALL-type induction therapy.
      Patients 2 and 3 with T-ALL and AML with AML dominance responded poorly to
      prednisolone. Patient 2 was resistant to AML-type therapy; patient 3 was
      resistant to ALL-type induction therapy until day 15. However, all 3 patients
      eventually achieved complete remission after ALL-type induction therapy. Thus,
      ALL-type induction therapy should be initiated for bilineal acute leukemia even
      with AML-dominant, poor prednisolone response, or poor early response features.

PMID- 30198962
TI  - Mucoepidermoid Carcinoma in Warthin Tumor of the Parotis in Childhood: A Case
      Report and Review of the Literature.
AB  - Mucoepidermoid carcinoma arising in Warthin tumor of the parotid gland is an
      extremely rare entity. This is so far described only in the adult age group, and
      only one patient has been reported in the pediatric age group until today.
      Herein, we describe our patient and review the literature. This was a case of a 9
      year-old girl admitted with a painless swelling in the left side of her face for
      at least 2 weeks. Histopathologic examination of total parotidectomy specimens
      revealed mucoepidermoid carcinoma arising in the Warthin tumor. This case is the
      youngest patient reported to date.

PMID- 30198963
TI  - Early Experience With Nonporous Polyethylene Barrier Sheet in Orbital Fracture
      Repair.
AB  - PURPOSE: The aim of this study was to evaluate the efficacy of the nonporous
      polyethylene barrier sheet as an alternative for nylon foil (SupraFOIL) implants
      in repair of orbital fractures. METHODS: This is a prospective, case series using
      the Stryker 0.4-mm-thick nonporous polyethylene barrier sheet in all patients
      over the age of 18 years presenting with orbital fractures from December 2014 to
      June 2015. Patient's age, location of fracture, etiology of injury, presence of
      preoperative restriction and diplopia, and postoperative diplopia and/or
      enophthalmos was recorded. Institutional review board approval was received, and
      consent was obtained from all participants. Patients were followed for at least 6
      months when possible. Scanning electron microscopy was used to compare the
      thickness, surface characteristics, and porosity of the nonporous polyethylene
      barrier and nylon foil implants. Beam deflection testing was also performed to
      compare the biomechanical properties of each implant. RESULTS: Forty-six patients
      who underwent repair of orbital fractures with the nonporous polyethylene barrier
      sheet were included in this series. Average age was 43.3 years (range: 18-84
      years). Twenty-six of 46 patients (56.5%) were males, and 20 (43.4%) were
      females. The most common causes of injuries were assault (38.3%), falls (25.5%),
      motor vehicle accident (14.9%), and sports related (10.5%). Twenty of 46 patients
      (43.4%) had isolated orbital floor, and 2 patients (4.3%) had isolated medial
      wall fractures. Fifteen patients (32.6%) had combined floor and medial wall
      fractures involving the inferomedial orbital strut, and 9 (19.6%) had floor
      fractures associated with zygomaticomaxillary complex or lateral wall fractures.
      Twenty-eight patients (60.9%) had preoperative diplopia. Timing of surgery was
      between 3 and 55 days, with the median of 11.5 days. Five of 46 patients (10.8%)
      had residual diplopia at their 1-week postoperative visit, 4 of those patients'
      diplopia had resolved at 2 months postoperatively. One patient had residual
      diplopia at 6-month follow up. Electron microscopy showed that the 0.4-mm
      nonporous polyethylene barrier implant was thinner (0.33 mm) than expected and
      thinner than 0.4-mm SupraFOIL (0.38 mm). Scanning electron microscopy exhibited
      that the surface of the nonporous polyethylene barrier was smooth and nonporous.
      Beam deflection testing showed that for small forces (<100 mN), the 2 materials
      behaved nearly identically, but at higher forces, the nonporous polyethylene
      implant exhibited less stiffness. CONCLUSIONS: The use of nonporous polyethylene
      barrier sheet implant for orbital fracture repair is a safe and effective
      alternative to nonporous nylon foil implants. There were no complications and one
      case of residual diplopia (2.1%) in this case series.

PMID- 30198964
TI  - Scanning Electron Microscopic Features of the Inferior Meatal Nasolacrimal Duct
      Openings.
AB  - PURPOSE: The aim of this study was to examine the ultrastructural features of the
      nasolacrimal duct (NLD) openings in the inferior meatus. METHODS: Five openings
      of the NLD in the inferior meati from 5 sagittal head sections of 3 cadavers were
      studied. Each of the openings were completely excised with 2 mm margins on all
      sides and transported to the laboratory in 2.5% glutaraldehyde. The analysis was
      performed using the standard protocols of scanning electron microscopy. The ends,
      edges, and surfaces were studied along with the mucosal folds, if any, guarding
      the edge of the openings. RESULTS: Of the 5 NLD openings studied, 4 were of the
      sulcus variety and 1 was of the shape of a fissure. The fissure opening had a
      guarding anterior edge mucosal fold. The luminal surfaces of the openings were
      mostly smooth with focal defined glandular structures. Occasional heterogenous
      areas with prominent and extensive well-defined glands lined by ciliated columnar
      epithelium were noted. There were presence of mucosal folds on the floor of the
      sulci of the openings giving an appearance of a subsulcus. CONCLUSIONS: The
      luminal surfaces of the NLD openings in the inferior meati shows mucosal folds
      reflected on themselves and cavernous vessels throughout the expanse of the
      openings. Tear rheology at the NLD opening and the physiologic role of subsulci
      need to be investigated further.

PMID- 30198965
TI  - Color Doppler Flow Imaging of Retrobulbar Ocular Blood Flow Changes in Retinal
      Artery Occlusions Caused by Cosmetic Facial Filler Injections.
AB  - PURPOSE: This study aimed to evaluate the effects of retinal artery occlusions
      caused by cosmetic facial filler injections on the retrobulbar blood flow
      parameters. METHODS: This was a retrospective, noncomparative case series. Ten
      consecutive patients with fundus artery occlusions caused by facial filler
      injections were evaluated using color Doppler flow imaging (CDFI). The peak
      systolic velocity and end diastolic velocity of the ophthalmic artery, central
      retinal artery, and posterior ciliary arteries were determined. The clinical
      features, including the filler material, injection site, best-corrected visual
      acuity, fundus fluorescein angiography, and associated ocular and systemic
      manifestations were also collected. RESULTS: Injected materials included
      autologous fat (7 cases) and hyaluronic acid (3 cases). In 6 of the patients with
      ophthalmic artery occlusions, the CDFI showed no or drastic declines in the
      retrobulbar blood flow in the ophthalmic artery, central retinal artery, and
      posterior ciliary arteries. In 3 of the patients with central retinal artery
      occlusions, the CDFI showed no or a grossly decreased retrobulbar blood flow in
      the central retinal artery. In one patient with anterior ischemic optic
      neuropathy, the CDFI showed decreased end diastolic velocities and increased
      pulsatility and resistance indices in the central retinal artery, posterior
      ciliary arteries, and ophthalmic artery. During the follow-up period, the
      retrobulbar blood flow recovered to some degree. Overall, ophthalmic artery
      occlusion patients receiving autologous fat may have neurologic complications.
      CONCLUSIONS: The results suggest that the retrobulbar ocular blood flows measured
      with CDFI were distinctly different in the different types of ophthalmic artery
      occlusion. Color Doppler flow imaging could provide a practicable and convenient
      method for the diagnosis and follow up of retinal artery occlusions caused by
      cosmetic facial filler injections.

PMID- 30198966
TI  - A Surgical Technique for the Management of Tractional Retinal Detachment in
      Aggressive Posterior Retinopathy of Prematurity Treated With Intravitreal
      Bevacizumab.

PMID- 30198967
TI  - RANIBIZUMAB IN PIGMENT EPITHELIAL TEARS SECONDARY TO AGE-RELATED MACULAR
      DEGENERATION: A Prospective Study.
AB  - PURPOSE: To assess efficacy of intravitreal ranibizumab in retinal pigment
      epithelium tears secondary to neovascular age-related macular degeneration.
      METHODS: The Ranibizumab In Pigment epithelial tears secondary to age-related
      macular degeneration (RIP) study is a prospective, single-arm, multicenter,
      investigator-initiated trial. Twenty four eyes of 24 patients with a retinal
      pigment epithelium tear secondary to age-related macular degeneration received
      monthly intravitreal injection of 0.5mg ranibizumab for 12 months, together with
      monthly assessments of morphologic and functional efficacy parameters. Primary
      outcome measure was mean best-corrected visual acuity at final visit compared
      with baseline. RESULTS: Mean best-corrected visual acuity remained stable over
      the 12-month study period with 50.3 Early Treatment of Diabetic Retinopathy Study
      letters (+/-18.7; Snellen equivalent 20/100) at baseline and 52.9 letters (+/
      19.7; Snellen equivalent 20/100) at final visit (P = 0.39). One eye (4%)
      experienced a vision loss of >=15 letters, and 2 eyes (8%) gained >=15 letters.
      Mean central retinal thickness decreased from 571 um (+/-185 um) to 436 um (+/
      171 um; P = 0.0001). Vision-related quality of life was stable with a mean VFQ-25
      score of 79.0 (+/-10.8) at baseline and 74.3 (+/-13.9) at final visit (P = 0.12).
      CONCLUSION: In retinal pigment epithelium tears secondary to age-related macular
      degeneration, monthly intravitreal ranibizumab therapy results in stabilization
      of visual acuity over 12 months.

PMID- 30198968
TI  - Correspondence.

PMID- 30198969
TI  - ASSOCIATION BETWEEN CHOROIDAL CAVERNS AND CHOROIDAL VASCULAR HYPERPERMEABILITY IN
      EYES WITH PACHYCHOROID DISEASES.
AB  - PURPOSE: To investigate the association between choroidal caverns, choroidal
      vascular hyperpermeability (CVH), and pachyvessels in eyes with pachychoroid
      disease. METHODS: This was a retrospective review of swept-source optical
      coherence tomography and indocyanine green angiography imaging performed on eyes
      with pachychoroid disease. RESULTS: Imaging from 21 eyes with pachychoroid
      disease entities (8 eyes with pachychoroid pigment epitheliopathy, 11 eyes with
      central serous chorioretinopathy, and 3 eyes with pachychoroid neovasculopathy)
      from 11 patients (mean 49.5 years, male/female: 10/1, all white) was available
      for review. In all study eyes, pachyvessels traversed the areas of CVH visible in
      mid- and late-phase indocyanine green angiography. A total of 504 choroidal
      caverns were identified in 11 study eyes (52%). Of the 504 choroidal caverns, 445
      (88%) were seen within the areas of CVH compared with 59 (12%), which were
      detected outside the areas of CVH (P < 0.001). Eyes with multiple caverns had an
      increased choroidal thickness when compared with eyes with <=1 cavern (P <
      0.001). CONCLUSION: Choroidal caverns, found primarily in the areas of
      indocyanine green angiography CVH traversed by pachyvessels, were detected in 52%
      of eyes with pachychoroid disease. The presence of choroidal caverns in these
      cases may indicate a loss of normal choroidal architecture associated with
      dilated Haller layer veins and increased choroidal thickness.

PMID- 30198970
TI  - Correspondence.

PMID- 30198971
TI  - Reply.

PMID- 30198972
TI  - Normal brain metabolism on FDG PET/MRI during childhood and adolescence.
AB  - OBJECTIVE: The aim was to investigate normal patterns of brain metabolism
      determined by F-fluorodeoxyglucose positron emission tomography (FDG PET)/MRI
      during childhood and adolescence. PATIENTS AND METHODS: A retrospective analysis
      was carried out on all paediatric patients who underwent FDG PET/MRI at our
      institution between March 2016 and August 2017. Exclusion criteria were
      neurological disease, central nervous system metastases, previous
      chemotherapy/radiotherapy, general anaesthesia/sedation and medications suspected
      to affect cerebral metabolism. Standardized uptake value (SUV)mean and SUVmax
      were calculated for 12 brain grey matter regions. Subgroup analysis of childhood
      (<=10 years old) and adolescence (>=11 years old) was also carried out. RESULTS:
      From 492 PET/MRI scans, 28 patients (11 children, 17 adolescents) were deemed
      representative of normal brain metabolism. SUVmean and SUVmax increased with age
      in all regions. The highest rates of increasing SUVmean were in the thalamus,
      basal ganglia, frontal lobes, insula and occipital lobes. Higher SUVmean was
      found in the right frontal, right lateral temporal, right temporal pole, right
      cingulate/paracingulate, right thalamus, left occipital, left basal ganglia, left
      insula and left cerebellum compared with the contralateral side. This SUVmean
      asymmetry was present in both childhood and adolescence in the majority of
      regions. The highest rates of increasing SUVmax with age were in the occipital
      lobes, frontal lobes, thalamus and central region. There was no asymmetry in
      SUVmax in the majority of regions. CONCLUSION: This FDG PET/MRI study shows that
      normal brain metabolism measured by SUVmean and SUVmax increases with age in all
      regions, proceeding at different rates between distinct anatomical sites. Our
      results suggest that there is mild asymmetry in SUVmean, but mostly symmetric
      SUVmax during normal development.

PMID- 30198973
TI  - New era of PET/CT in breast cancer: high-resolution PET/dfCT.
AB  - OBJECTIVE: To determine whether breast cancer staging differs between high
      resolution (HR) and standard-resolution (SR) PET/computed tomography acquisition.
      PATIENTS AND METHODS: This retrospective study included 39 women with breast
      cancer referred for staging. Images were assessed for the number of primary
      breast lesions with the corresponding size and the average maximum standardized
      uptake value (SUVmax), the anatomical site of fluorine-18-fluorodeoxyglucose-avid
      lymph nodes (LNs) with their SUVmax, and the number and type (lytic/blastic) of
      metastatic bone lesions. RESULTS: On HR, 42 breast tumor lesions with a size
      range of 0.30 cm up to 12.00 cm were detected versus 34 breast tumor lesions on
      SR. One hundred and forty-one versus 90 axillary LNs were detected on HR versus
      SR, respectively. Pathology reports were available for 60 axillary LNs out of the
      total 141 identified on HR. Rates for HR versus SR sensitivity, true positivity,
      false positivity, and false negativity are as follows: 92 versus 75%, 92 versus
      75%, 2 versus 0%, and 7 versus 25%. The higher detection rate of axillary LN on
      HR was significant (P<0.001), but not the number of nodes detected (P=0.091).
      SUVmax for breast tumor lesions (P=0.225) and axillary LNs (P=0.134) were not
      significant. Three (8%) patients had a change in staging and management.
      CONCLUSION: HR detected primary breast lesions and metastatic LNs missed on SR,
      which led to change in staging and management. In addition, HR images provided
      higher SUVmax, which enabled a more comfortable localization, especially when SR
      presented borderline values. Finally, HR images decreased the number of gray zone
      lesions, especially in axillary LN detection.

PMID- 30198974
TI  - 18F-FDG-PET metabolic metrics and International Prognostic Score for risk
      assessment in HIV-infected patients with Hodgkin lymphoma.
AB  - OBJECTIVES: Baseline metabolic metrics on fluorine-18-fluorodeoxyglucose PET (F
      FDG PET) have prognostic value in Hodgkin lymphoma. International Prognostic
      Score (IPS) is used in the risk stratification of Hodgkin lymphoma. We compared
      the metabolic indices in HIV-infected and the IPS in HIV-infected and uninfected
      patients with Hodgkin lymphoma. PATIENTS AND METHODS: We retrospectively reviewed
      the data of HIV-infected and HIV-uninfected patients with classic Hodgkin
      lymphoma who had F-FDG PET for staging and compared the maximum standardized
      uptake value, mean standardized uptake value, metabolic tumor volume, and total
      lesion glycolysis between the two groups. We also compared the IPS and other
      prognostic indicators and correlated them with the metabolic indices in the two
      groups. RESULTS: We studied 160 patients, which included 57 patients who were
      infected with HIV. The mean age was 33.84+/-11.88 years, with 38% (n=61) being
      female. The median cluster of differentiation 4 count and HIV viral load were 259
      cells/mm and 4837.50 copies/ml, respectively. No significant difference in
      maximum standardized uptake value, mean standardized uptake value, metabolic
      tumor volume, and total lesion glycolysis between the two groups was found. Among
      the seven parameters of the IPS, only male sex (HIV-uninfected group higher,
      P=0.005) and serum albumin less than 4 g/dl were significantly different. The
      other parameters were not significantly different between the two groups. Other
      prognostic indicators including bulky disease, extranodal involvement, and the
      number of nodal groups involved were not significantly different between the two
      groups. CONCLUSION: There was no significant difference in F-FDG metabolic
      parameters, IPS, and other risk indicators between HIV-infected and HIV
      uninfected patients with Hodgkin lymphoma.

PMID- 30198975
TI  - Re: "Frontalis Muscle Contraction and the Role of Visual Deprivation and Eyelid
      Proprioception".

PMID- 30198976
TI  - Reply re: "Frontalis Muscle Contraction and the Role of Visual Deprivation and
      Eyelid Proprioception".

PMID- 30198977
TI  - Re: "A Prospective Randomized Comparative Clinical Trial to Analyze Pain and
      Surgical Outcomes Between Frontal Nerve Blocks and Subconjunctival Anesthesia for
      Conjunctival Mullerectomy Resection".

PMID- 30198978
TI  - Reply re: "A Prospective Randomized Comparative Clinical Trial to Analyze Pain
      and Surgical Outcomes Between Frontal Nerve Blocks and Subconjunctival Anesthesia
      For Conjunctival Mullerectomy Resection".

PMID- 30198979
TI  - Re: "Can We Improve the Tolerance of an Ocular Prosthesis by Enhancing Its
      Surface Finish?"

PMID- 30198980
TI  - Reply Re: "Can We Improve the Tolerance of an Ocular Prosthesis by Enhancing Its
      Surface Finish?"

PMID- 30198981
TI  - Necrotizing Orbital Cellulitis Secondary to Odontogenic Streptococcus
      constellatus.
AB  - A 69-year-old woman with orbital cellulitis secondary to odontogenic
      Streptococcus constellatus was transferred to the authors' institution for
      surgical management of infection refractory to intravenous antibiotics. She
      underwent debridement with preservation of the globe, recovering full motility.
      Visual recovery was limited by optic nerve ischemia. This case supports the
      importance of urgent surgical drainage in necrotizing orbital infections
      secondary to odontogenic Streptococcus constellatus.

PMID- 30198982
TI  - Sino-Orbital Fungal Infection by Tilletiopsis minor, a Rare Human Pathogen,
      Diagnosed by Internal Transcribed Spacer Sequencing.
AB  - Orbital infection can be caused by numerous pathogens, and accurate diagnosis
      informs appropriate therapy. The authors report a case of a 78-year-old man with
      well-controlled diabetes mellitus and recurrent sino-orbital infection following
      multiple surgical procedures with negative microbiologic results. This case
      presented a diagnostic and treatment challenge and was aided by the use of
      internal transcribed spacer sequencing for pathogen identification. The fungal
      pathogen, Tilletiopsis minor, has not previously been described as a human
      pathogen in the sinus and orbit. This report describes a novel orbital pathogen
      and highlights the importance of diagnostic diligence and utilizing internal
      transcribed spacer sequencing in the workup of atypical orbital infection.

PMID- 30198984
TI  - Dementia: An Opportunity for Grace.

PMID- 30198983
TI  - Cyst Excision and Globe Preservation in a Case of Microphthalmos With a Large
      Orbital Cyst and Visual Potential.
AB  - Congenital microphthalmos belongs to a spectrum of diseases ranging from true
      anophthalmos to congenital clinical anophthalmos to microphthalmos. These
      conditions are frequently associated with an orbitopalpebral cyst, and
      pathologically, this represents a failure in the closure of the embryonic fissure
      at the 7-14 mm stage of gestation. The cyst develops as an outpouching from the
      eyeball and is generally helpful as it provides a stimulus for the orbit to
      expand. The general management guideline is to retain the cyst till it provides a
      stimulus for the orbit to expand and then to consider aspiration and
      sclerotherapy once orbital expansion is achieved. However, in eyes that have
      visual potential, sclerotherapy is contraindicated. The authors present an
      unusual case of a mildly microphthalmic eye with visual potential and a
      communicating cyst that was excised with a good result. The challenges faced in
      the excision of the communicating cyst with a wide pedicle and the management of
      the case are highlighted.

PMID- 30198985
TI  - NCF @ Work.

PMID- 30198986
TI  - NCFI: An Essential Vitamin Injection.

PMID- 30198987
TI  - Etc.

PMID- 30198988
TI  - Divine Appointments.

PMID- 30198989
TI  - Nursing in the Church.

PMID- 30198990
TI  - Student TXT.

PMID- 30198991
TI  - Moving Beyond Dilemma Ethics.

PMID- 30198993
TI  - Serving on a Board of Nursing: Pursuing Justice, Mercy, and Humility.
AB  - What is it like to serve on a State Board of Nursing (BON)? How does one deal
      with the weight of the responsibility, the discomfort of inexperience in the
      role, and integrate personal faith with the professional expectations of
      administering justice and discipline? The author defines the patients cared for
      in the BON role and the balance of discipline with care for nurses.

PMID- 30198992
TI  - The Long Journey of Alzheimer's Disease.
AB  - The growing elderly population is creating record numbers of individuals with
      Alzheimer's disease (AD) and other dementias. Nursing has an unprecedented
      opportunity to rethink how we care for adults with dementia, reduce the burden of
      caregivers, and preserve the personhood of patients. This article reviews AD and
      dementia pathophysiology, history, screening, stigma, treatments and
      interventions, and caregiver support. A nurse's journey with her mother with AD
      imparts the meaning of patient dignity.

PMID- 30198994
TI  - Promoting Successful Aging Through Faith Community Nursing.
AB  - Promotion of successful aging is imperative for the growing population of U.S.
      adults 65 and older, who will outnumber those 18 and under by 2035. Faith
      community nurses (FCNs) provide interventions targeting health promotion and
      disease prevention, with a focus on faith and health. This study examined the
      most frequently documented interventions and attended services provided to older
      adults by FCNs. A secondary analysis of data from the web-based Henry Ford Macomb
      Hospital Faith Community Nursing/Health Ministries Documentation and Reporting
      System reveals how FCNs are contributing to successful aging.

PMID- 30198995
TI  - Assessing Religious Commitment and Satisfaction: The Religious Surrender and
      Attendance Satisfaction Scale.
AB  - Survey instruments have been developed to measure whether someone claims to be
      religious but do not address the degree to which someone is satisfied with their
      religious commitment. The Religious Surrender and Attendance Satisfaction Scale
      (RSASS) was revised to measure both a person's level of religious commitment and
      satisfaction with level of religious commitment. This study was conducted to
      determine initial validity for the satisfaction portion of the RSASS. Construct
      validity measures provided initial confirmation of the utility of RSASS as a
      measure of satisfaction with religious commitment, that can be used by nurses in
      practice and research.

PMID- 30198996
TI  - Helping Bridge the Great Divides: Supporting Nurse Communication at End of Life.
AB  - Many, especially newer, nurses lack the experience for nuanced skillful
      communication at end of life. This study incorporated the End-of-Life Nursing
      Education Consortium (ELNEC) Core Curriculum Communication module into a nurse
      residency program and tested for change in attitudes toward end-of-life (EOL)
      care. Researchers found significant differences in attitudes toward care of the
      dying before and after the ELNEC training, and between nurses with greater than
      and less than 5 years experience. Findings support that ELNEC education can
      significantly impact nurse attitudes about EOL care.

PMID- 30198997
TI  - Intercessory Prayer: Differentiating the Source.

PMID- 30198998
TI  - The Birthing of Jesus.

PMID- 30198999
TI  - Double-Edged Sword: Course Evaluations.

PMID- 30199000
TI  - Living in the Diagnosis of Cancer.

PMID- 30199001
TI  - Chat Room.

PMID- 30199002
TI  - PulseBeats.

PMID- 30199003
TI  - Spirituality and Interprofessional Healthcare Education: An Exploratory Study.
AB  - Undergraduate and graduate programs for healthcare professions are inconsistent
      in curricular offerings and incorporation of spiritual training. This study
      reviewed perceptions and opinions about spiritual care held by students at an
      American university. Data were collected using the Spirituality and Spiritual
      Care Rating Scale and one open-ended question. Findings indicated that many
      students were comfortable incorporating spirituality into practice, and they
      desired additional training. As to how students would apply spirituality to their
      practice, themes of facilitating connection, holistic care, spiritual
      interventions, and benefits of spirituality were identified.

PMID- 30199004
TI  - Building God's Kingdom Through Strengths-Based Teaching.
AB  - Teaching nursing students using a strengths-based instructional framework
      provides an encouraging and positive learning environment. The authors advocate
      learning one's own strengths and gifts through the Strengthsfinder tool, then
      applying that self-understanding to teach in a way that instills confidence in
      students.

PMID- 30199005
TI  - Proceedings of the 6th Biennial Innovations in Faith-Based Nursing Conference.

PMID- 30199006
TI  - The Long Journey of Alzheimer's Disease.

PMID- 30199007
TI  - Promoting Successful Aging Through Faith Community Nursing.

PMID- 30199008
TI  - [Advanced Practice Nursing in emergency care, a proposal for the change:
      Systematic review].
AB  - BACKGROUND: Advanced Practice Nursing is an unknown role in our country. The aim
      of the study is to show the results of this model in emergency services for its
      future implementation in the Spanish health system. METHODS: Revision sistematica
      de las bases de datos de The Cochrane Controlled, Web Of Science, Cinahl, Cuiden,
      LILACS, Guia Salud y Cochrane Database of Systematic Reviews. Se utilizaron
      escalas validadas para la seleccion de 14 articulos finales, siguiendo el formato
      PRISMA. RESULTS: Favourable results were observed, with maximum waiting times of
      53 minutes and average time of stay of 45 minutes. There were less than 8% of
      cases of unexpected readmissions. Favourable results were also found regarding
      safety and patient satisfaction. CONCLUSIONS: The implementation of this figure
      could be beneficial for the improvement of the public health system, increasing
      the quality of care in terms of efficiency.

PMID- 30199009
TI  - High Throughput, Absolute Determination of the Content of a Selected Protein at
      Tissue Levels Using Quantitative Dot Blot Analysis (QDB).
AB  - Lacking a convenient, quantitative, high throughput immunoblot method for
      absolute determination of the content of a specific protein at cellular and
      tissue level significantly hampers the progress in proteomic research. Results
      derived from currently available immunoblot techniques are also relative,
      preventing any efforts to combine independent studies with a large-scale analysis
      of protein samples. In this study, we demonstrate the process of quantitative dot
      blot analysis (QDB) to achieve absolute quantification in a high throughput
      format. Using a commercially available protein standard, we are able to determine
      the absolute content of capping actin protein, gelsolin-like (CAPG) in protein
      samples prepared from three different mouse tissues (kidney, spleen, and
      prostate) together with a detailed explanation of the experimental details. We
      propose the QDB analysis as a convenient, quantitative, high throughput
      immunoblot method of absolute quantification of individual proteins at the
      cellular and tissue level. This method will substantially aid biomarker
      validation and pathway verification in various areas of biological and biomedical
      research.

PMID- 30199010
TI  - Organotypic Culture Method to Study the Development Of Embryonic Chicken Tissues.
AB  - The embryonic chicken is commonly used as a reliable model organism for
      vertebrate development. Its accessibility and short incubation period makes it
      ideal for experimentation. Currently, the study of these developmental pathways
      in the chicken embryo is conducted by applying inhibitors and drugs at localized
      sites and at low concentrations using a variety of methods. In vitro tissue
      culturing is a technique that enables the study of tissues separated from the
      host organism, while simultaneously bypassing many of the physical limitations
      present when working with whole embryos, such as the susceptibility of embryos to
      high doses of potentially lethal chemicals. Here, we present an organotypic
      culturing protocol for culturing the embryonic chicken half head in vitro, which
      presents new opportunities for the examination of developmental processes beyond
      the currently established methods.

PMID- 30199011
TI  - Analysis of Epididymal Protein Synthesis and Secretion.
AB  - The mammalian epididymis generates one of the most complex intraluminal fluids of
      any endocrine gland in order to support the post-testicular maturation and
      storage of spermatozoa. Such complexity arises due to the combined secretory and
      absorptive activity of the lining epithelial cells. Here, we describe the
      techniques for the analysis of epididymal protein synthesis and secretion by
      focusing on the model protein family of dynamin (DNM) mechanoenzymes; large
      GTPases that have the potential to regulate bi-directional membrane trafficking
      events. For the study of protein expression in epididymal tissue, we describe
      robust methodology for immunofluorescence labeling of target proteins in paraffin
      embedded sections and the subsequent detection of the spatial distribution of
      these proteins via immunofluorescence microscopy. We also describe optimized
      methodology for the isolation and characterization of exosome like vesicles,
      known as epididymosomes, which are secreted into the epididymal lumen to
      participate in intercellular communication with maturing sperm cells. As a
      complementary approach, we also describe the immunofluorescence detection of
      target proteins in an SV40-immortalized mouse caput epididymal epithelial
      (mECap18) cell line. Moreover, we discuss the utility of the mECap18 cell line as
      a suitable in vitro model with which to explore the regulation of epididymal
      secretory activity. For this purpose, we describe the culturing requirements for
      the maintenance of the mECap18 cell line and the use of selective pharmacological
      inhibition regimens that are capable of influencing their secretory protein
      profile. The latter are readily assessed via harvesting of conditioned culture
      medium, concentration of secreted proteins via trichloroacetic acid/acetone
      precipitation and their subsequent analysis via SDS-PAGE and immunoblotting. We
      contend that these combined methods are suitable for the analysis of alternative
      epididymal protein targets as a prelude to determining their functional role in
      sperm maturation and/or storage.

PMID- 30199012
TI  - A Flexible Low Cost Hydroponic System for Assessing Plant Responses to Small
      Molecules in Sterile Conditions.
AB  - A wide range of studies in plant biology are performed using hydroponic cultures.
      In this work, an in vitro hydroponic growth system designed for assessing plant
      responses to chemicals and other substances of interest is presented. This system
      is highly efficient in obtaining homogeneous and healthy seedlings of the C3 and
      C4 model species Arabidopsis thaliana and Setaria viridis, respectively. The
      sterile cultivation avoids algae and microorganism contamination, which are known
      limiting factors for plant normal growth and development in hydroponics. In
      addition, this system is scalable, enabling the harvest of plant material on a
      large scale with minor mechanical damage, as well as the harvest of individual
      parts of a plant if desired. A detailed protocol demonstrating that this system
      has an easy and low-cost assembly, as it uses pipette racks as the main platform
      for growing plants, is provided. The feasibility of this system was validated
      using Arabidopsis seedlings to assess the effect of the drug AZD-8055, a chemical
      inhibitor of the target of rapamycin (TOR) kinase. TOR inhibition was efficiently
      detected as early as 30 min after an AZD-8055 treatment in roots and shoots.
      Furthermore, AZD-8055-treated plants displayed the expected starch-excess
      phenotype. We proposed this hydroponic system as an ideal method for plant
      researchers aiming to monitor the action of plant inducers or inhibitors, as well
      as to assess metabolic fluxes using isotope-labeling compounds which, in general,
      requires the use of expensive reagents.

PMID- 30199014
TI  - Designing CAD/CAM Surgical Guides for Maxillary Reconstruction Using an In-house
      Approach.
AB  - Computer-aided design/computer-assisted manufacturing (CAD/CAM) is now being
      evaluated as a preparative technique for maxillofacial surgery. Because this
      technique is expensive and available in only limited areas of the world, we
      developed a novel CAD/CAM surgical guide using an in-house approach. By using the
      CAD software, the maxillary resection area and cutting planes and the fibular
      cutting planes and angles are determined. Once the resection area is decided, the
      necessary faces are extracted using a Boolean modifier. These superficial faces
      are united to fit the surface of the bones and thickened to stabilize the solids.
      Not only the cutting guides for the fibula and maxilla but also the location
      arrangement of the transferred bone segments is defined by thickening the
      superficial faces. The CAD design is recorded as .stl files and three
      dimensionally (3-D) printed as actual surgical guides. To check the accuracy of
      the guides, model surgery using 3-D-printed facial and fibular models is
      performed. These methods may be used to assist surgeons where commercial guides
      are not available.

PMID- 30199013
TI  - Quantitative Analysis of Alternative Pre-mRNA Splicing in Mouse Brain Sections
      Using RNA In Situ Hybridization Assay.
AB  - Alternative splicing (AS) occurs in more than 90% of human genes. The expression
      pattern of an alternatively spliced exon is often regulated in a cell type
      specific fashion. AS expression patterns are typically analyzed by RT-PCR and RNA
      seq using RNA samples isolated from a population of cells. In situ examination of
      AS expression patterns for a particular biological structure can be carried out
      by RNA in situ hybridization (ISH) using exon-specific probes. However, this
      particular use of ISH has been limited because alternative exons are generally
      too short to design exon-specific probes. In this report, the use of BaseScope, a
      recently developed technology that employs short antisense oligonucleotides in
      RNA ISH, is described to analyze AS expression patterns in mouse brain sections.
      Exon 23a of neurofibromatosis type 1 (Nf1) is used as an example to illustrate
      that short exon-exon junction probes exhibit robust hybridization signals with
      high specificity in RNA ISH analysis on mouse brain sections. More importantly,
      signals detected with exon inclusion- and skipping-specific probes can be used to
      reliably calculate the percent spliced in values of Nf1 exon 23a expression in
      different anatomical areas of a mouse brain. The experimental protocol and
      calculation method for AS analysis are presented. The results indicate that
      BaseScope provides a powerful new tool to assess AS expression patterns in situ.

PMID- 30199015
TI  - Probing the Limits of Egg Recognition Using Egg Rejection Experiments Along
      Phenotypic Gradients.
AB  - Brood parasites lay their eggs in other females' nests, leaving the host parents
      to hatch and rear their young. Studying how brood parasites manipulate hosts into
      raising their young and how hosts detect parasitism provide important insights in
      the field of coevolutionary biology. Brood parasites, such as cuckoos and
      cowbirds, gain an evolutionary advantage because they do not have to pay the
      costs of rearing their own young. However, these costs select for host defenses
      against all developmental stages of parasites, including eggs, their young, and
      adults. Egg rejection experiments are the most common method used to study host
      defenses. During these experiments, a researcher places an experimental egg in a
      host nest and monitors how hosts respond. Color is often manipulated, and the
      expectation is that the likelihood of egg discrimination and the degree of
      dissimilarity between the host and experimental egg are positively related. This
      paper serves as a guide for conducting egg rejection experiments from describing
      methods for creating consistent egg colors to analyzing the findings of such
      experiments. Special attention is given to a new method involving uniquely
      colored eggs along color gradients that has the potential to explore color biases
      in host recognition. Without standardization, it is not possible to compare
      findings between studies in a meaningful way; a standard protocol within this
      field will allow for increasingly accurate and comparable results for further
      experiments.

PMID- 30199016
TI  - A Networked Desktop Virtual Reality Setup for Decision Science and Navigation
      Experiments with Multiple Participants.
AB  - Investigating the interactions among multiple participants is a challenge for
      researchers from various disciplines, including the decision sciences and spatial
      cognition. With a local area network and dedicated software platform,
      experimenters can efficiently monitor the behavior of the participants that are
      simultaneously immersed in a desktop virtual environment and digitalize the
      collected data. These capabilities allow for experimental designs in spatial
      cognition and navigation research that would be difficult (if not impossible) to
      conduct in the real world. Possible experimental variations include stress during
      an evacuation, cooperative and competitive search tasks, and other contextual
      factors that may influence emergent crowd behavior. However, such a laboratory
      requires maintenance and strict protocols for data collection in a controlled
      setting. While the external validity of laboratory studies with human
      participants is sometimes questioned, a number of recent papers suggest that the
      correspondence between real and virtual environments may be sufficient for
      studying social behavior in terms of trajectories, hesitations, and spatial
      decisions. In this article, we describe a method for conducting experiments on
      decision-making and navigation with up to 36 participants in a networked desktop
      virtual reality setup (i.e., the Decision Science Laboratory or DeSciL). This
      experiment protocol can be adapted and applied by other researchers in order to
      set up a networked desktop virtual reality laboratory.

PMID- 30199018
TI  - A Western Blotting Protocol for Small Numbers of Hematopoietic Stem Cells.
AB  - Hematopoietic stem cells (HSCs) are rare cells, with the mouse bone marrow
      containing only ~25,000 phenotypic long term repopulating HSCs. A Western
      blotting protocol was optimized and suitable for the analysis of small numbers of
      HSCs (500 - 15,000 cells). Phenotypic HSCs were purified, accurately counted, and
      directly lysed in Laemmli sample buffer. Lysates containing equal numbers of
      cells were analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis
      (SDS-PAGE), and the blot was prepared and processed following standard Western
      blotting protocols. Using this protocol, 2,000 - 5,000 HSCs can be routinely
      analyzed, and in some cases data can be obtained from as few as 500 cells,
      compared to the 20,000 to 40,000 cells reported in most publications. This
      protocol should be generally applicable to other hematopoietic cells, and enables
      the routine analysis of small numbers of cells using standard laboratory
      procedures.

PMID- 30199017
TI  - Dual Effects of Melanoma Cell-derived Factors on Bone Marrow Adipocytes
      Differentiation.
AB  - The crosstalk between bone marrow adipocytes and tumor cells may play a critical
      role in the process of bone metastasis. A variety of methods are available for
      studying the significant crosstalk; however, a two-dimensional transwell system
      for coculture remains a classic, reliable, and easy way for this crosstalk study.
      Here, we present a detailed protocol that shows the coculture of bone marrow
      adipocytes and melanoma cells. Nevertheless, such a coculture system could not
      only contribute to the study of cell signal transductions of cancer cells induced
      by bone marrow adipocytes, but also to the future mechanistic study of bone
      metastasis which may reveal new therapeutic targets for bone metastasis.

PMID- 30199019
TI  - Agarose-based Tissue Mimicking Optical Phantoms for Diffuse Reflectance
      Spectroscopy.
AB  - This protocol describes how to make agarose-based tissue-mimicking phantoms and
      demonstrates how to determine their optical properties using a conventional
      optical system with an integrating sphere. Measuring systems for the acquisition
      of the diffuse reflectance and total transmittance spectra are constructed with a
      broadband white light source, a light guide, an achromatic lens, an integrating
      sphere, a sample holder, an optical fiber probe, and a multi-channel
      spectrometer. An acrylic mold consisting of two rectangular acrylic pieces and a
      U-shaped acrylic piece is constructed to create an epidermal phantom and a dermal
      phantom with whole blood. The application of a sodium dithionite (Na2S2O4)
      solution to the dermal phantom enables the researcher to deoxygenate hemoglobin
      in red blood cells distributed in the dermal phantom. The inverse Monte Carlo
      simulation with the diffuse reflectance and total transmittance spectra measured
      by a spectrometer with an integrating sphere is performed to determine the
      absorption coefficient spectrum ua(lambda) and the reduced scattering coefficient
      spectrum us'(lambda) of each layer phantom. A two-layered phantom mimicking the
      diffuse reflectance of human skin tissue is also demonstrated by piling up the
      epidermal phantom on the dermal phantom.

PMID- 30199020
TI  - Heterogeneous Removal of Water-Soluble Ruthenium Olefin Metathesis Catalyst from
      Aqueous Media Via Host-Guest Interaction.
AB  - A highly efficient transition metal catalyst removal method is developed. The
      water-soluble catalyst contains a newly-designed NHC ligand for the catalyst
      removal via host-guest interactions. The new NHC ligand possesses an adamantyl
      (guest) tethered linear ethylene glycol units for hydrophobic inclusion into the
      cavity of a beta-cyclodextrin (beta-CD) host compound. The new NHC ligand was
      applied to a Ru-based olefin metathesis catalyst. The Ru catalyst demonstrated
      excellent activity in representative ring-closing metathesis (RCM) and ring
      opening metathesis polymerization (ROMP) reactions in aqueous media as well as
      organic solvent, CH2Cl2. After the reaction was complete, the lingering Ru
      residue was removed from the aqueous solution with the efficiency of more than
      99% (53 ppm of Ru residue) by simple filtration utilizing a host-guest
      interaction between insoluble silica-grafted beta-CD (host) and the adamantyl
      moiety (guest) on the catalyst. The new Ru catalyst also demonstrated high
      removal efficiency via extraction when the reaction is run in organic solvent by
      partitioning the crude reaction mixture between layers of diethyl ether and
      water. In this way, the catalyst stays in aqueous layer only. In organic layer,
      the residual Ru amount was only 0.14 ppm in the RCM reactions of diallyl
      compounds.

PMID- 30199021
TI  - Analysis of AtHIRD11 Intrinsic Disorder and Binding Towards Metal Ions by
      Capillary Gel Electrophoresis and Affinity Capillary Electrophoresis.
AB  - Plants are strongly dependent on their environment. In order to adjust to
      stressful changes (e.g., drought and high salinity), higher plants evolve classes
      of intrinsically disordered proteins (IDPs) to reduce oxidative and osmotic
      stress. This article uses a combination of capillary gel electrophoresis (CGE)
      and mobility shift affinity electrophoresis (ACE) in order to describe the
      binding behavior of different conformers of the IDP AtHIRD11 from Arabidopsis
      thaliana. CGE is used to confirm the purity of AtHIRD11 and to exclude fragments,
      posttranslational modifications, and other impurities as reasons for complex peak
      patterns. In this part of the experiment, the different sample components are
      separated by a viscous gel inside a capillary by their different masses and
      detected with a diode array detector. Afterward, the binding behavior of the
      sample towards various metal ions is investigated by ACE. In this case, the
      ligand is added to the buffer solution and the shift in migration time is
      measured in order to determine whether a binding event has occurred or not. One
      of the advantages of using the combination of CGE and ACE to determine the
      binding behavior of an IDP is the possibility to automate the gel electrophoresis
      and the binding assay. Furthermore, CGE shows a lower limit of detection than the
      classical gel electrophoresis and ACE is able to determine the manner of binding
      a ligand in a fast manner. In addition, ACE can also be applied to other charged
      species than metal ions. However, the use of this method for binding experiments
      is limited in its ability to determine the number of binding sites. Nevertheless,
      the combination of CGE and ACE can be adapted for characterizing the binding
      behavior of any protein sample towards numerous charged ligands.

PMID- 30199023
TI  - Microparticle Manipulation by Standing Surface Acoustic Waves with Dual-frequency
      Excitations.
AB  - We demonstrate a method for increasing the tuning ability of a standing surface
      acoustic wave (SSAW) for microparticles manipulation in a lab-on-a-chip (LOC)
      system. The simultaneous excitation of the fundamental frequency and its third
      harmonic, which is termed as dual-frequency excitation, to a pair of interdigital
      transducers (IDTs) could generate a new type of standing acoustic waves in a
      microfluidic channel. Varying the power and the phase in the dual-frequency
      excitation signals results in a reconfigurable field of the acoustic radiation
      force applied to the microparticles across the microchannel (e.g., the number and
      location of the pressure nodes and the microparticle concentrations at the
      corresponding pressure nodes). This article demonstrates that the motion time of
      the microparticle to only one pressure node can be reduced ~2-fold at the power
      ratio of the fundamental frequency greater than ~90%. In contrast, there are
      three pressure nodes in the microchannel if less than this threshold.
      Furthermore, adjusting the initial phase between the fundamental frequency and
      the third harmonic results in different motion rates of the three SSAW pressure
      nodes, as well as in the percentage of microparticles at each pressure node in
      the microchannel. There is a good agreement between the experimental observation
      and the numerical predictions. This novel excitation method can easily and non
      invasively integrate into the LOC system, with a wide tenability and only a few
      changes to the experimental set-up.

PMID- 30199022
TI  - Detection of Viruses from Bioaerosols Using Anion Exchange Resin.
AB  - This protocol demonstrates a customized bioaerosol sampling method for viruses.
      In this system, anion exchange resin is coupled with liquid impingement-based air
      sampling devices for efficacious concentration of negatively-charged viruses from
      bioaerosols. Thus, the resin serves as an additional concentration step in the
      bioaerosol sampling workflow. Nucleic acid extraction of the viral particles is
      then performed directly from the anion exchange resin, with the resulting sample
      suitable for molecular analyses. Further, this protocol describes a custom-built
      bioaerosol chamber capable of generating virus-laden bioaerosols under a variety
      of environmental conditions and allowing for continuous monitoring of
      environmental variables such as temperature, humidity, wind speed, and aerosol
      mass concentration. The main advantage of using this protocol is increased
      sensitivity of viral detection, as assessed via direct comparison to an
      unmodified conventional liquid impinger. Other advantages include the potential
      to concentrate diverse negatively-charged viruses, the low cost of anion exchange
      resin (~$0.14 per sample), and ease of use. Disadvantages include the inability
      of this protocol to assess infectivity of resin-adsorbed viral particles, and
      potentially the need for the optimization of the liquid sampling buffer used
      within the impinger.

PMID- 30199024
TI  - Isolation of Mandibular Gland Reservoir Contents from Bornean 'Exploding Ants'
      (Formicidae) for Volatilome Analysis by GC-MS and MetaboliteDetector.
AB  - The aim of this manuscript is to present a protocol describing the metabolomic
      analysis of Bornean 'exploding ants' belonging to the Colobopsis cylindrica
      (COCY) group. For this purpose, the model species C. explodens is used. Ants
      belonging to the minor worker caste possess distinctive hypertrophied mandibular
      glands (MGs). In territorial combat, they use the viscous contents of their
      enlarged mandibular gland reservoirs (MGRs) to kill rival arthropods in
      characteristic suicidal 'explosions' by voluntary rupture of the gastral
      integument (autothysis). We show the dissection of worker ants of this species
      for the isolation of the gastral portion of the wax-like MGR contents as well as
      listing the necessary steps required for solvent-extraction of the therein
      contained volatile compounds with subsequent gas chromatography-mass spectrometry
      (GC-MS) analysis and putative identification of metabolites contained in the
      extract. The dissection procedure is performed under cooled conditions and
      without the use of any dissection buffer solution to minimize the changes in the
      chemical composition of the MGR contents. After solvent-based extraction of
      volatile metabolites contained therein, the necessary steps for analyzing the
      samples via liquid-injection-GC-MS are presented. Lastly, data processing and
      putative metabolite identification with the use of the open-source software
      MetaboliteDetector is shown. With this approach, the profiling and identification
      of volatile metabolites in MGRs of ants belonging to the COCY group via GC-MS and
      the MetaboliteDetector software become possible.

PMID- 30199025
TI  - Synthesis of Bimetallic Pt/Sn-based Nanoparticles in Ionic Liquids.
AB  - We demonstrate a method for the synthesis of bimetallic nanoparticles consisting
      of Pt and Sn. A synthesis strategy is used in which the particular physico
      chemical properties of ionic liquids (ILs) are exploited to control both
      nucleation and growth processes. The nanoparticles form colloidal sols of very
      high colloidal stability in the IL, which is particularly interesting in view of
      their use as quasi-homogeneous catalysts. Procedures for both nanoparticle
      extraction in conventional solvents and for nanoparticle precipitation are
      presented. The size, structure and composition of the synthesized nanocrystals
      are confirmed using inductively coupled plasma atomic emission spectroscopy (ICP
      AES), X-ray diffraction analysis (XRD) and transmission electron microscopy (TEM)
      with energy-dispersive X-ray spectroscopy (EDX). By this, we show that the
      nanocrystals are random-type alloy and of small (2-3 nm) size. The catalytic
      activity and selectivity in the hydrogenation of alpha,beta-unsaturated aldehydes
      is tested in a semi-continuous batch-type reactor. In this context, the
      bimetallic Pt/Sn-based nanoparticles reveal a high selectivity towards the
      unsaturated alcohol.

PMID- 30199026
TI  - Tick Microbiome Characterization by Next-Generation 16S rRNA Amplicon Sequencing.
AB  - In recent decades, vector-borne diseases have re-emerged and expanded at alarming
      rates, causing considerable morbidity and mortality worldwide. Effective and
      widely available vaccines are lacking for a majority of these diseases,
      necessitating the development of novel disease mitigation strategies. To this
      end, a promising avenue of disease control involves targeting the vector
      microbiome, the community of microbes inhabiting the vector. The vector
      microbiome plays a pivotal role in pathogen dynamics, and manipulations of the
      microbiome have led to reduced vector abundance or pathogen transmission for a
      handful of vector-borne diseases. However, translating these findings into
      disease control applications requires a thorough understanding of vector
      microbial ecology, historically limited by insufficient technology in this field.
      The advent of next-generation sequencing approaches has enabled rapid, highly
      parallel sequencing of diverse microbial communities. Targeting the highly
      conserved 16S rRNA gene has facilitated characterizations of microbes present
      within vectors under varying ecological and experimental conditions. This
      technique involves amplification of the 16S rRNA gene, sample barcoding via PCR,
      loading samples onto a flow cell for sequencing, and bioinformatics approaches to
      match sequence data with phylogenetic information. Species or genus-level
      identification for a high number of replicates can typically be achieved through
      this approach, thus circumventing challenges of low detection, resolution, and
      output from traditional culturing, microscopy, or histological staining
      techniques. Therefore, this method is well-suited for characterizing vector
      microbes under diverse conditions but cannot currently provide information on
      microbial function, location within the vector, or response to antibiotic
      treatment. Overall, 16S next-generation sequencing is a powerful technique for
      better understanding the identity and role of vector microbes in disease
      dynamics.

PMID- 30199027
TI  - A Simplified and Efficient Method to Isolate Primary Human Keratinocytes from
      Adult Skin Tissue.
AB  - Primary human keratinocytes isolated from fresh skin tissues and their expansion
      in vitro have been widely used for laboratory research and for clinical
      applications. The conventional isolation method of human keratinocytes involves a
      two-step sequential enzymatic digestion procedure, which has been proven to be
      inefficient in generating primary cells from adult tissues due to the low cell
      recovery rate and reduced cell viability. We recently reported an advanced method
      to isolate human primary epidermal progenitor cells from skin tissues that
      utilizes the Rho kinase inhibitor Y-27632 in the medium. Compared with the
      traditional protocol, this new method is simpler, easier, and less time
      consuming, and increases epithelial stem cell yield and enhances their stem cell
      characteristics. Moreover, the new methodology does not require the separation of
      the epidermis from the dermis, and, therefore, is suitable for isolating cells
      from different types of adult tissues. This new isolation method overcomes the
      major shortcomings of conventional methods and is more suitable for producing
      large numbers of epidermal cells with high potency both for laboratory and for
      clinical applications. Here, we describe the new method in detail.

PMID- 30199028
TI  - Plate-based Large-scale Cultivation of Caenorhabditis elegans: Sample Preparation
      for the Study of Metabolic Alterations in Diabetes.
AB  - Culturing Caenorhabditis elegans (C. elegans) in a large-scale manner on agar
      plates can be time-consuming and difficult. This protocol describes a simple and
      inexpensive method to obtain a large number of animals for the isolation of
      proteins to proceed with a western blot, mass spectrometry, or further proteomics
      analyses. Furthermore, an increase of nematode numbers for immunostainings and
      the integration of multiple analyses under the same culturing conditions can
      easily be achieved. Additionally, a transfer between plates with different
      experimental conditions is facilitated. Common techniques in plate culture
      involve the transfer of a single C. elegans using a platinum wire and the
      transfer of populated agar chunks using a scalpel. However, with increasing
      nematode numbers, these techniques become overly time-consuming. This protocol
      describes the large-scale culture of C. elegans including numerous steps to
      minimize the impact of the sample preparation on the physiology of the worm.
      Fluid and shear stress can alter the lifespan of and metabolic processes in C.
      elegans, thus requiring a detailed description of the critical steps in order to
      retrieve reliable and reproducible results. C. elegans is a model organism,
      consisting of neuronal cells for up to one-third, but lacking blood vessels, thus
      providing the possibility to investigate solely neuronal alterations independent
      of vascular control. Recently, early neurodegeneration in diabetic retinopathy
      was found prior to vascular alterations. Thus, C. elegans is of special interest
      for studying general mechanisms of diabetic complications. For example, an
      increased formation of advanced glycation end products (AGEs) and reactive oxygen
      species (ROS) is observed, which are reproducibly found in C. elegans. Protocols
      to handle samples of adequate size for a broader spectrum of investigations are
      presented here, exemplified by the study of diabetes-induced biochemical
      alterations. In general, this protocol can be useful for studies requiring large
      C. elegans numbers and in which liquid culture is not suitable.

PMID- 30199029
TI  - An In Vivo Mouse Model to Measure Naive CD4 T Cell Activation, Proliferation and
      Th1 Differentiation Induced by Bone Marrow-derived Dendritic Cells.
AB  - Quantification of naive CD4 T cell activation, proliferation, and differentiation
      to T helper 1 (Th1) cells is a useful way to assess the role played by T cells in
      an immune response. This protocol describes the in vitro differentiation of bone
      marrow (BM) progenitors to obtain granulocyte macrophage colony-stimulating
      factor (GM-CSF) derived-dendritic cells (DCs). The protocol also describes the
      adoptive transfer of ovalbumin peptide (OVAp)-loaded GM-CSF-derived DCs and naive
      CD4 T cells from OTII transgenic mice in order to analyze the in vivo activation,
      proliferation, and Th1 differentiation of the transferred CD4 T cells. This
      protocol circumvents the limitation of purely in vivo methods imposed by the
      inability to specifically manipulate or select the studied cell population.
      Moreover, this protocol allows studies in an in vivo environment, thus avoiding
      alterations to functional factors that may occur in vitro and including the
      influence of cell types and other factors only found in intact organs. The
      protocol is a useful tool for generating changes in DCs and T cells that modify
      adaptive immune responses, potentially providing important results to understand
      the origin or development of numerous immune associated diseases.

PMID- 30199030
TI  - In Vitro Canine Neutrophil Extracellular Trap Formation: Dynamic and Quantitative
      Analysis by Fluorescence Microscopy.
AB  - In response to invading pathogens, neutrophils release neutrophil extracellular
      traps (NETs), which are extracellular networks of DNA decorated with histones and
      antimicrobial proteins. Excessive NET formation (NETosis) and citH3 release
      during sepsis is associated with multiple organ dysfunction and mortality in mice
      and humans but its implications in dogs are unknown. Herein, we describe a
      technique to isolate canine neutrophils from whole blood for observation and
      quantification of NETosis. Leukocyte-rich plasma, generated by dextran
      sedimentation, is separated by commercially available density gradient separation
      media and granulocytes collected for cell count and viability testing. To observe
      real-time NETosis in live neutrophils, cell permeant and cell impermeant
      fluorescent nucleic acid stains are added to neutrophils activated either by
      lipopolysaccharide (LPS) or phorbol 12-myristate 13-acetate (PMA). Changes in
      nuclear morphology and NET formation are observed over time by fluorescence
      microscopy. In vitro NETosis is further characterized by co-colocalization of
      cell-free DNA (cfDNA), myeloperoxidase (MPO) and citrullinated histone H3 (citH3)
      using a modified double-immunolabelling protocol. To objectively quantify NET
      formation and citH3 expression using fluorescence microscopy, NETs and citH3
      positive cells are quantified in a blinded manner using available software. This
      technique is a specific assay to evaluate the in vitro capacity of canine
      neutrophils to undergo NETosis.

PMID- 30199031
TI  - Genetic Incorporation of Biosynthesized L-dihydroxyphenylalanine (DOPA) and Its
      Application to Protein Conjugation.
AB  - L-dihydroxyphenylalanine (DOPA) is an amino acid found in the biosynthesis of
      catecholamines in animals and plants. Because of its particular biochemical
      properties, the amino acid has multiple uses in biochemical applications. This
      report describes a protocol for the genetic incorporation of biosynthesized DOPA
      and its application to protein conjugation. DOPA is biosynthesized by a tyrosine
      phenol-lyase (TPL) from catechol, pyruvate, and ammonia, and the amino acid is
      directly incorporated into proteins by the genetic incorporation method using an
      evolved aminoacyl-tRNA and aminoacyl-tRNA synthetase pair. This direct
      incorporation system efficiently incorporates DOPA with little incorporation of
      other natural amino acids and with better protein yield than the previous genetic
      incorporation system for DOPA. Protein conjugation with DOPA-containing proteins
      is efficient and site-specific and shows its usefulness for various applications.
      This protocol provides protein scientists with detailed procedures for the
      efficient biosynthesis of mutant proteins containing DOPA at desired sites and
      their conjugation for industrial and pharmaceutical applications.

PMID- 30199032
TI  - Functional Characterization of Carboxylesterases in Insecticide Resistant House
      Flies, Musca Domestica.
AB  - Carboxylesterase-mediated metabolism is thought to play a major role in
      insecticide resistance in various insects. Several carboxylesterase genes were
      found up-regulated in the resistant house fly strain, whereas their roles in
      conferring insecticide resistance remained to be explored. Here, we designed a
      protocol for the functional characterization of carboxylesterases. Three example
      experiments are presented: (1) expression and isolation of carboxylesterase
      proteins through a baculovirus-mediated insect Spodoptera frugiperda (Sf9) cell
      expression system; (2) a cell-based MTT (3-[4, 5-dimethykthiazol-2-yl]-2, 5
      diphenyltetrazolium bromide) cytotoxicity assay to measure the tolerance of
      insect cells to different permethrin treatments; and (3) in vitro metabolic
      studies to explore the metabolic capabilities of carboxylesterases toward
      permethrin. The carboxylesterase gene MdalphaE7 was cloned from a resistant house
      fly strain ALHF and used to construct a recombinant baculovirus for Sf9 cells
      infection. The cell viabilities against different permethrin treatments were
      measured with the MTT assay. The enhanced cell tolerance of the experimental
      group (MdalphaE7-recombinant baculovirus infected cells) compared with those of
      the control groups (CAT-recombinant baculovirus infected cells and GFP
      recombinant baculovirus infected cells) to permethrin treatments suggested the
      capabilities of MdalphaE7 in metabolizing insecticides, thereby protecting cells
      from chemical damages. Besides that, carboxylesterase proteins were expressed in
      insect Sf9 cells and isolated to conduct an in vitro metabolic study. Our results
      indicated a significant in vitro metabolic efficiency of MdalphaE7 toward
      permethrin, directly indicating the involvement of carboxylesterases in
      metabolizing insecticides and thus conferring insecticide resistance in house
      flies.

PMID- 30199034
TI  - Benchtop Immobilized Metal Affinity Chromatography, Reconstitution and Assay of a
      Polyhistidine Tagged Metalloenzyme for the Undergraduate Laboratory.
AB  - Benchtop immobilized metal affinity chromatography (IMAC), of polyhistidine
      tagged proteins is easily mastered by undergraduate students and has become the
      most widely used protein purification method in the modern literature. But, the
      application of affinity chromatography to metal binding proteins, especially
      those with redox sensitive metals such as iron, is often limited to laboratories
      with access to a glove box - equipment that is not routinely available in the
      undergraduate laboratory. In this article, we demonstrate our benchtop methods
      for isolation, IMAC purification and metal-ion reconstitution of a poly-histidine
      tagged, redox-active, non-heme iron binding extradiol dioxygenase and the assay
      of the dioxygenase with varied substrate concentrations and saturating oxygen.
      These methods are executed by undergraduate students and implemented in the
      undergraduate teaching and research laboratory with instrumentation that is
      accessible and affordable at primarily undergraduate institutions.

PMID- 30199033
TI  - Three-Dimensional Ultrasonic Needle Tip Tracking with a Fiber-Optic Ultrasound
      Receiver.
AB  - Ultrasound is frequently used for guiding minimally invasive procedures, but
      visualizing medical devices is often challenging with this imaging modality. When
      visualization is lost, the medical device can cause trauma to critical tissue
      structures. Here, a method to track the needle tip during ultrasound image-guided
      procedures is presented. This method involves the use of a fiber-optic ultrasound
      receiver that is affixed within the cannula of a medical needle to communicate
      ultrasonically with the external ultrasound probe. This custom probe comprises a
      central transducer element array and side element arrays. In addition to
      conventional two-dimensional (2D) B-mode ultrasound imaging provided by the
      central array, three-dimensional (3D) needle tip tracking is provided by the side
      arrays. For B-mode ultrasound imaging, a standard transmit-receive sequence with
      electronic beamforming is performed. For ultrasonic tracking, Golay-coded
      ultrasound transmissions from the 4 side arrays are received by the hydrophone
      sensor, and subsequently the received signals are decoded to identify the needle
      tip's spatial location with respect to the ultrasound imaging probe. As a
      preliminary validation of this method, insertions of the needle/hydrophone pair
      were performed in clinically realistic contexts. This novel ultrasound
      imaging/tracking method is compatible with current clinical workflow, and it
      provides reliable device tracking during in-plane and out-of-plane needle
      insertions.

PMID- 30199035
TI  - Complete and Partial Aortic Occlusion for the Treatment of Hemorrhagic Shock in
      Swine.
AB  - Hemorrhage remains the leading cause of preventable deaths in trauma.
      Endovascular management of non-compressible torso hemorrhage has been at the
      forefront of trauma care in recent years. Since complete aortic occlusion
      presents serious concerns, the concept of partial aortic occlusion has gained a
      growing attention. Here, we present a large animal model of hemorrhagic shock to
      investigate the effects of a novel partial aortic balloon occlusion catheter and
      compare it with a catheter that works on the principles of complete aortic
      occlusion. Swine are anesthetized and instrumented in order to conduct controlled
      fixed-volume hemorrhage, and hemodynamic and physiological parameters are
      monitored. Following hemorrhage, aortic balloon occlusion catheters are inserted
      and inflated in the supraceliac aorta for 60 min, during which the animals
      receive whole-blood resuscitation as 20% of the total blood volume (TBV).
      Following balloon deflation, the animals are monitored in a critical care setting
      for 4 h, during which they receive fluid resuscitation and vasopressors as
      needed. The partial aortic balloon occlusion demonstrated improved distal mean
      arterial pressures (MAPs) during the balloon inflation, decreased markers of
      ischemia, and decreased fluid resuscitation and vasopressor use. As swine
      physiology and homeostatic responses following hemorrhage have been well
      documented and are like those in humans, a swine hemorrhagic shock model can be
      used to test various treatment strategies. In addition to treating hemorrhage,
      aortic balloon occlusion catheters have become popular for their role in cardiac
      arrest, cardiac and vascular surgery, and other high-risk elective surgical
      procedures.

PMID- 30199036
TI  - A Novel Saturation Mutagenesis Approach: Single Step Characterization of
      Regulatory Protein Binding Sites in RNA Using Phosphorothioates.
AB  - Gene regulation plays an important role in development. Numerous DNA- and RNA
      binding proteins bind their target sequences with high specificity to control
      gene expression. These regulatory proteins control gene expression either at the
      level of DNA (transcription) or at the level of RNA (pre-mRNA splicing,
      polyadenylation, mRNA transport, decay, and translation). Identification of
      regulatory sequences helps understand not only how a gene is switched on or off,
      but also which downstream genes are regulated by a particular regulatory protein.
      Here, we describe a one-step approach that allows saturation mutagenesis of a
      protein binding site in RNA. It involves doping DNA template with non-wild-type
      nucleotides within the binding site, synthesis of separate RNAs with each
      phosphorothioate nucleotide, and isolation of the bound fraction following
      incubation with protein. Interference from non-wild-type nucleotides results in
      their preferential exclusion from the protein-bound fraction. This is monitored
      by gel electrophoresis following selective chemical cleavage with iodine of
      phosphodiester bonds containing phosphorothioates (phosphorothioate mutagenesis
      or PTM). This single-step saturation mutagenesis approach is applicable to the
      characterization of any protein binding site in RNA.

PMID- 30199037
TI  - Hyaluronic-Acid Based Hydrogels for 3-Dimensional Culture of Patient-Derived
      Glioblastoma Cells.
AB  - Glioblastoma (GBM) is the most common, yet most lethal, central nervous system
      cancer. In recent years, many studies have focused on how the extracellular
      matrix (ECM) of the unique brain environment, such as hyaluronic acid (HA),
      facilitates GBM progression and invasion. However, most in vitro culture models
      include GBM cells outside of the context of an ECM. Murine xenografts of GBM
      cells are used commonly as well. However, in vivo models make it difficult to
      isolate the contributions of individual features of the complex tumor
      microenvironment to tumor behavior. Here, we describe an HA hydrogel-based, three
      dimensional (3D) culture platform that allows researchers to independently alter
      HA concentration and stiffness. High molecular weight HA and polyethylene glycol
      (PEG) comprise hydrogels, which are crosslinked via Michael-type addition in the
      presence of live cells. 3D hydrogel cultures of patient-derived GBM cells exhibit
      viability and proliferation rates as good as, or better than, when cultured as
      standard gliomaspheres. The hydrogel system also enables incorporation of ECM
      mimetic peptides to isolate effects of specific cell-ECM interactions. Hydrogels
      are optically transparent so that live cells can be imaged in 3D culture.
      Finally, HA hydrogel cultures are compatible with standard techniques for
      molecular and cellular analyses, including PCR, Western blotting and
      cryosectioning followed by immunofluorescence staining.

PMID- 30199038
TI  - Generation of Electronic Cigarette Aerosol by a Third-Generation Machine-Vaping
      Device: Application to Toxicological Studies.
AB  - Electronic-cigarette (e-cig) devices use heat to produce an inhalable aerosol
      from a liquid (e-liquid) composed mainly of humectants, nicotine, and flavoring
      chemicals. The aerosol produced includes fine and ultrafine particles, and
      potentially nicotine and aldehydes, which can be harmful to human health. E-cig
      users inhale these aerosols and, with the third-generation of e-cig devices,
      control design features (resistance and voltage) in addition to the choice of e
      liquids, and the puffing profile. These are key factors that can significantly
      impact the toxicity of the inhaled aerosols. E-cig research, however, is
      challenging and complex mostly due to the absence of standardized assessments and
      to the numerous varieties of e-cig models and brands, as well as e-liquid flavors
      and solvents that are available on the market. These considerations highlight the
      urgent need to harmonize e-cig research protocols, starting with e-cig aerosol
      generation and characterization techniques. The current study focuses on this
      challenge by describing a detailed step-by-step e-cig aerosol generation
      technique with specific experimental parameters that are thought to be realistic
      and representative of real-life exposure scenarios. The methodology is divided
      into four sections: preparation, exposure, post-exposure analysis, plus cleaning
      and maintenance of the device. Representative results from using two types of e
      liquid and various voltages are presented in terms of mass concentration,
      particle size distribution, chemical composition and cotinine levels in mice.
      These data demonstrate the versatility of the e-cig exposure system used, aside
      from its value for toxicological studies, as it allows for a broad range of
      computer-controlled exposure scenarios, including automated representative vaping
      topography profiles.

PMID- 30199039
TI  - Force-Clamp Rheometry for Characterizing Protein-based Hydrogels.
AB  - Here, we describe a force-clamp rheometry method to characterize the
      biomechanical properties of protein-based hydrogels. This method uses an analog
      proportional-integral-derivative (PID) system to apply controlled-force protocols
      on cylindrical protein-based hydrogel samples, which are tethered between a
      linear voice-coil motor and a force transducer. During operation, the PID system
      adjusts the extension of the hydrogel sample to follow a predefined force
      protocol by minimizing the difference between the measured and set-point forces.
      This unique approach to protein-based hydrogels enables the tethering of
      extremely low-volume hydrogel samples (< 5 uL) with different protein
      concentrations. Under force-ramp protocols, where the applied stress increases
      and decreases linearly with time, the system enables the study of the elasticity
      and hysteresis behaviors associated with the (un)folding of proteins and the
      measurement of standard elastic and viscoelastic parameters. Under constant
      force, where the force pulse has a step-like shape, the elastic response, due to
      the change in force, is decoupled from the viscoelastic response, which comes
      from protein domain unfolding and refolding. Due to its low-volume sample and
      versatility in applying various mechanical perturbations, force-clamp rheometry
      is optimized to investigate the mechanical response of proteins under force using
      a bulk approach.

PMID- 30199040
TI  - Differentiation, Maintenance, and Analysis of Human Retinal Pigment Epithelium
      Cells: A Disease-in-a-dish Model for BEST1 Mutations.
AB  - Although over 200 genetic mutations in the human BEST1 gene have been identified
      and linked to retinal degenerative diseases, the pathological mechanisms remain
      elusive mainly due to the lack of a good in vivo model for studying BEST1 and its
      mutations under physiological conditions. BEST1 encodes an ion channel, namely
      BESTROPHIN1 (BEST1), which functions in retinal pigment epithelium (RPE);
      however, the extremely limited accessibility to native human RPE cells represents
      a major challenge for scientific research. This protocol describes how to
      generate human RPEs bearing BEST1 disease-causing mutations by induced
      differentiation from human pluripotent stem cells (hPSCs). As hPSCs are self
      renewable, this approach allows researchers to have a steady source of hPSC-RPEs
      for various experimental analyses, such as immunoblotting, immunofluorescence,
      and patch clamp, and thus provides a very powerful disease-in-a-dish model for
      BEST1-associated retinal conditions. Notably, this strategy can be applied to
      study RPE (patho)physiology and other genes of interest natively expressed in
      RPE.

PMID- 30199041
TI  - Endogenous Protein Tagging in Human Induced Pluripotent Stem Cells Using
      CRISPR/Cas9.
AB  - A protocol is presented for generating human induced pluripotent stem cells
      (hiPSCs) that express endogenous proteins fused to in-frame N- or C-terminal
      fluorescent tags. The prokaryotic CRISPR/Cas9 system (clustered regularly
      interspaced short palindromic repeats/CRISPR-associated 9) may be used to
      introduce large exogenous sequences into genomic loci via homology directed
      repair (HDR). To achieve the desired knock-in, this protocol employs the
      ribonucleoprotein (RNP)-based approach where wild type Streptococcus pyogenes
      Cas9 protein, synthetic 2-part guide RNA (gRNA), and a donor template plasmid are
      delivered to the cells via electroporation. Putatively edited cells expressing
      the fluorescently tagged proteins are enriched by fluorescence activated cell
      sorting (FACS). Clonal lines are then generated and can be analyzed for precise
      editing outcomes. By introducing the fluorescent tag at the genomic locus of the
      gene of interest, the resulting subcellular localization and dynamics of the
      fusion protein can be studied under endogenous regulatory control, a key
      improvement over conventional overexpression systems. The use of hiPSCs as a
      model system for gene tagging provides the opportunity to study the tagged
      proteins in diploid, nontransformed cells. Since hiPSCs can be differentiated
      into multiple cell types, this approach provides the opportunity to create and
      study tagged proteins in a variety of isogenic cellular contexts.

PMID- 30199042
TI  - Preparation of Stable Bicyclic Aziridinium Ions and Their Ring-Opening for the
      Synthesis of Azaheterocycles.
AB  - Bicyclic aziridinium ions were generated by the removal of an appropriate leaving
      group through internal nucleophilic attack by nitrogen atom in the aziridine
      ring. The utility of bicyclic aziridinium ions, specifically 1
      azoniabicyclo[3.1.0]hexane and 1-azoniabicyclo[4.1.0]heptane tosylate highlighted
      in the aziridine ring openings by the nucleophile with the release of the ring
      strain to yield the corresponding ring-expanded azaheterocycles such as
      pyrrolidine, piperidine and azepane with diverse substituents on the ring in
      regio- and stereospecific manner. Herein, we report a simple and convenient
      method for the preparation of the stable 1-azabicyclo[4.1.0]heptane tosylate
      followed by selective ring opening via a nucleophilic attack either at the bridge
      or at the bridgehead carbon to yield piperidine and azepane rings, respectively.
      This synthetic strategy allowed us to prepare biologically active natural
      products containing piperidine and azepane motif including sedamine,
      allosedamine, fagomine and balanol in highly efficient manner.

PMID- 30199044
TI  - Isolation and Identification of Extravascular Immune Cells of the Heart.
AB  - The immune system is an essential component of a healthy heart. The myocardium is
      home to a rich population of different immune cell subsets with functional
      compartmentalization both during steady state and during different forms of
      inflammation. Until recently, the study of immune cells in the heart required the
      use of microscopy or poorly developed digestion protocols, which provided enough
      sensitivity during severe inflammation but were unable to confidently identify
      small - but key - populations of cells during steady state. Here, we discuss a
      simple method combining enzymatic (collagenase, hyaluronidase and DNAse) and
      mechanical digestion of murine hearts preceded by intravascular administration of
      fluorescently-labelled antibodies to differentiate small but unavoidable
      intravascular cell contaminants. This method generates a suspension of isolated
      viable cells that can be analyzed by flow cytometry for identification,
      phenotyping and quantification, or further purified with fluorescence-activated
      cell sorting or magnetic bead separation for transcriptional analysis or in vitro
      studies. We include an example of a step-by-step flow cytometric analysis to
      differentiate the key macrophage and dendritic cell populations of the heart. For
      a medium sized experiment (10 hearts) the completion of the procedure requires 2
      3 h.

PMID- 30199045
TI  - [Risk factors of regional lymph node metastases in pT1 colorectal cancer].
AB  - AIM: To identify risk factors of lymph node metastases in patients with pT1
      rectal cancer. MATERIAL AND METHODS: There were 43 patients aged 62.3+/-11.3
      years with pT1 rectal cancer who underwent mesorectal excision in 2012 - 2018.
      There were 34 (64%) females and 19 (36%) males. RESULTS: Histological examination
      revealed SM1-2 in 22/43 (51%) cases, SM3 - in 21/43 (49%) cases. Lymph node
      metastases were identified in specimens with submucosal invasion: SM3 - in 8/21
      (38.1%) cases and SM1-2 - in 3/22 (13.6%) cases (p=0.08). Logistic regression
      confirmed lymphovascular invasion (p=0.005) and mucosal and/or poorly
      differentiated carcinoma (p=0.014) as independent predictors of lymph node
      metastases. CONCLUSION: Lymphovascular invasion and poorly differentiated
      carcinoma are indications for transabdominal mesorectal excision.

PMID- 30199043
TI  - Catalytic Scavenging of Plant Reactive Oxygen Species In Vivo by Anionic Cerium
      Oxide Nanoparticles.
AB  - Reactive oxygen species (ROS) accumulation is a hallmark of plant abiotic stress
      response. ROS play a dual role in plants by acting as signaling molecules at low
      levels and damaging molecules at high levels. Accumulation of ROS in stressed
      plants can damage metabolites, enzymes, lipids, and DNA, causing a reduction of
      plant growth and yield. The ability of cerium oxide nanoparticles (nanoceria) to
      catalytically scavenge ROS in vivo provides a unique tool to understand and
      bioengineer plant abiotic stress tolerance. Here, we present a protocol to
      synthesize and characterize poly (acrylic) acid coated nanoceria (PNC), interface
      the nanoparticles with plants via leaf lamina infiltration, and monitor their
      distribution and ROS scavenging in vivo using confocal microscopy. Current
      molecular tools for manipulating ROS accumulation in plants are limited to model
      species and require laborious transformation methods. This protocol for in vivo
      ROS scavenging has the potential to be applied to wild type plants with broad
      leaves and leaf structure like Arabidopsis thaliana.

PMID- 30199046
TI  - [Risk factors of postoperative complications in patients with synchronous
      colorectal cancer liver metastases].
AB  - AIM: Univariate and multivariate analysis of various risk factors and morbidity
      in patients with synchronous colorectal cancer (CRC) liver metastases. MATERIAL
      AND METHODS: Prospective data of 173 patients with synchronous CRC liver
      metastases have been analyzed from January 2013 to February 2017 at the Ryzhikh
      State Coloproctology Research Center. RESULTS: In multivariate analysis
      significant risk factors of morbidity were age <=61 years, the largest liver
      metastasis >= 2.1 cm (odds ratio (OR) 2.99; 95% CI 1.4-6.5), number of liver
      metastases >1 (OR 2.5; 95% CI 1.1-5.5), bilobar liver injury (OR 2.5; 95% CI 1.3
      4.8), blood loss (OR 1.001; 95% CI 1.0001-1.002). Model for prediction of
      complications was constructed (AUC 0.79). CONCLUSION: Simultaneous surgery is not
      risk factor of complications. Probability of complications is increased in
      advanced tumor and consequently more traumatic surgery. Predictive model is
      useful for prognosis of complications and describes surgical experience of State
      Coloproctology Research Center.

PMID- 30199047
TI  - [Combined treatment of colorectal cancer followed by metastatic liver injury].
AB  - AIM: To increase the effectiveness of treatment of colorectal cancer followed by
      metastatic liver lesion. MATERIAL AND METHODS: This study included 319 patients
      with colorectal cancer and metastatic liver lesion Gennari grade I, II, and III
      for the period from 2002 to 2017. All patients received combined treatment. 107
      patients underwent liver resections: right-sided hemihepatectomy - 10, advanced
      right-sided hemihepatectomy - 7, left-sided hemihepatectomy - 9, triple
      segmentectomy - 33, bisegmentectomy - 29, segmentectomy - 19 cases.
      Radiofrequency ablation of liver metastases was performed in 105 patients. Cool
      tip device with a power of 200 W was used for destruction. Fifty-seven patients
      underwent microwave destruction of liver tumor (AveCure MWG 881, 34 W).
      Transarterial chemoembolization by doxorubicin and HepaSpheres 150-250 ng was
      applied in 34 patients. RESULTS: Annual, 2-, 3- and 5-year survival was 83.1%,
      73.5%, 60.2% and 24.6%, respectively after liver resection. RFA of liver
      metastases was followed by annual, 2- and 3-year survival near 73.5%, 53.3% and
      32.1%, respectively. In case of MWA of liver metastases annual survival was
      78.5%, 2-year - 63.3%, 3-year - 58.3%. CONCLUSION: Chemotherapy combined with
      targeted therapy, radiofrequency and microwave ablation is able to increase
      resectability up to 35-40% in patients with colorectal cancer followed by liver
      metastases. Minimally invasive procedures (RFA, MWA) reduce surgical risk in
      critically ill patients.

PMID- 30199048
TI  - [Minimally invasive treatment of rare forms of mechanical intestinal
      obstruction].
AB  - AIM: To develop medical algorithms for reduction of morbidity and mortality in
      rare forms of mechanical intestinal obstruction. MATERIAL AND METHODS: 17
      patients with mechanical intestinal obstruction have been operated in
      Sklifosovsky Research Institute for Emergency Care for the period 2010 - 2016.
      There were 13 women and 4 men aged 56 (44,5-74,5) years on the average.
      Phytobezoar was detected in 7 patients (41.2%), tumor in 7 patients (41.2%) and
      gallstone ileus in 3 patients (17.6%). RESULTS: There were no complications in
      group 1. In group 2 postoperative complications occurred in 3 patients:
      gastrocnemius vein thrombosis followed by successful medication (Clavien-Dindo
      type II), abdominal abscess drained under ultrasonic control (Clavien-Dindo type
      IIIa) and 1 (8.3%) death (Clavien-Dindo type V). Postoperative mortality in group
      2 was 8.3%. CONCLUSION: Despite small sample size and no statistically reliable
      results the advantages of minimally invasive access are obvious. However, further
      trials are required to ensure the reliability of the results.

PMID- 30199049
TI  - [Meta-analysis of management of colorectal anastomotic leakage].
AB  - AIM: To identify the most effective management of colorectal anastomosis failure
      via analysis of available literature sources. RESULTS: Systematic review included
      20 original trials. Effectiveness of redo interventions for colorectal
      anastomosis failure including open, laparoscopic, minimally invasive techniques
      (transanal drainage, endoscopic vacuum therapy, endoscopic drainage) was
      described. Anastomotic failure rate was 6.5%. Medication was effective in 57%
      (95% CI 34-77%) of cases. Redo open surgery was applied in 43% (95% CI 23-66%) of
      patients. Postoperative mortality was 21-27%. Redo laparoscopic procedure was
      performed in 61% (95% CI 50-70%) of cases for anastomotic failure after previous
      laparoscopy, incidence of conversion was 12% (95% CI 4-28%). Transanal drainage
      was effective in 85% (95% CI 61-94%) of cases, endoscopic vacuum therapy - in 82%
      (95% CI 74-87%), healing of anastomosis without need for colostomy was achieved
      in 16% (95% CI 9-26%) of cases. Endoscopic clipping for colorectal anastomotic
      defect was effective in 73.3-77% of cases. CONCLUSION: Redo surgery for
      anastomotic failure is associated with advanced mortality and need for permanent
      colostomy. Laparoscopic approach reduces incidence of complications after redo
      surgery and followed by better functional outcomes. Minimally invasive procedures
      are advisable for colorectal anastomosis failure without need for redo surgery.
      However, effectiveness of these methods is controversial due to few reports and
      no comparative trials.

PMID- 30199050
TI  - [Influence of anastomotic leakage on the long-term outcomes in patients with
      colorectal cancer].
AB  - Anastomotic leakage after surgery for colorectal cancer is a widely known factor
      aggravating immediate outcomes. At the same time, deterioration of oncological
      results is under much less attention. Long-term consequences of anastomotic
      leakage and possible mechanism of negative effect of this complication on long
      term results are reviewed in the article.

PMID- 30199051
TI  - [Prevention of colorectal anastomotic leakage by using of intraoperative
      fluorescent angiography: prospective trial data].
AB  - AIM: To evaluate the effect of intraoperative fluorescent angiography on the
      incidence of colorectal anastomosis failure. MATERIAL AND METHODS: Prospective,
      non-comparative study included 52 patients with rectal or sigmoid cancer who
      underwent surgery with stapled colorectal anastomosis. Intraoperative fluorescent
      angiography with indocyanine green was performed to determine colon perfusion.
      All patients underwent proctography with water-soluble contrast agent in 6-8 days
      after surgery in order to determine anastomotic leakage. RESULTS: Fluorescent
      angiography was followed by changed volume of proximal colectomy in 14 (27%)
      patients due to inadequate blood supply of intestinal wall at previous surgical
      level. Additionally, 1-5 cm of intestinal wall were excised. Postoperative
      anastomotic leakage occurred in 3 (5.8%) patients. CONCLUSION: Fluorescent
      angiography with indocyanine green is accompanied by reduced incidence of
      anastomotic failure in colorectal suregry.

PMID- 30199052
TI  - [Enhanced recovery program for colorectal surgery in cinical practice. Survey of
      surgeons of the Russian Federation].
AB  - AIM: To analyze RF surgeons' attitude to accelerated recovery program (ERP) and
      to determine how often it is used in daily work. MATERIAL AND METHODS: 223
      physicians from 42 Russian regions were interviewed in 2017. RESULTS: ERP is
      unknown among 11.7% of specialists; 8.9% heard about ERP but did not think that
      it is used in the Russian Federation; 16.6% know but do not apply the program;
      55.6% use some elements of ERP; complete application of ERP was found in 7.2% of
      surgeons. This technique is more often used by more active surgeons (p = 0.001)
      and less often - by female surgeons (p = 0.0066). The most controversial and
      difficult elements of ERP are administration of carbohydrate mixtures prior to
      surgery, optimal body temperature maintenance, restrictive protocol of infusion
      therapy, refusal mechanical intestinal depuration and routine abdominal drainage,
      and administrative control over the protocol. CONCLUSION: The majority of
      surgeons are ready to apply ERP. Some elements are difficult to apply for use in
      real healthcare. More educational activities are needed for wider and complete
      use of the protocol. New scientific available data should be used to improve this
      approach.

PMID- 30199054
TI  - [Seton drainage in sphincter-sparing treatment of rectal fistulas].
AB  - Sphincter-sparing procedures for rectal fistulas are becoming more popular among
      coloproctologists. However, the outcomes are not optimal that forces surgeons to
      seek new approaches in order to improve results. Seton drainage prior to radical
      stage is one of these methods. The effect of seton drainage on the outcomes is
      reviewed in the article. Elibrary, Pubmed and Google Scholar databases were
      analyzed. We have assessed 14 out of 151 trials for the period 1984 - 2017. There
      were no significant advantages of seton drainage compared with single-stage
      approach (chi2 = 3.84, p> 0.05, RR = 0.95, CI 95% 0.84 - 1.08). The same
      situation is observed for mucomuscular flap bringing down to close internal
      fistula. Fistula healing was more common after seton drainage deployment within 4
      - 8 weeks. Bringing down of the flap to anal canal should be preferred after
      drainage due to less incidence of recurrences. Further trials are necessary to
      determine advisability of seton drainage and optimal surgical approach.

PMID- 30199053
TI  - [Fast-tract: Therapist's role].
AB  - The modern model of inpatient surgical care of private and optimized
      state/govermental medical institutions allows us to change the paradigm of
      nosological attachment of the hospital bed to one profile of specialists for an
      adaptive model, when the wards can be reassigned depending on the needs of the
      hospital. In such multidisciplinary medical centers with mixed hospital beds
      without a nominal distinction in the nosological departments, a new therapeutic
      service is being developed - hospitalists, which provide a consistent curation of
      hospitalized patients, compensation of chronic therapeutic illnesses with
      patient's preparation for surgical interventions. Our work describes the
      experience of Fast Track recovery program with the active participation of a
      hospitalist in a surgical team, which is a new experience in the practice of
      Russian colorectal surgery.

PMID- 30199055
TI  - [Sphincter-sparing treatment of anal fissure].
AB  - Surgical treatment of the anal fissure is associated with unreasonably high risks
      of delayed development of fecal incontinence to gas or liquid stool. Standardized
      sphincter-preserving therapy, based on the pharmacological reduction of increased
      internal anal sphincter tone (chemical sphincterotomy) allows to improve
      significantly the results of the non-surgical approach of treating one of the
      most common pathology in proctological practice. Our work presents a
      retrospective analysis of the treatment of 295 patients with anal fissure treated
      with diltiazem ointment, nifedipine ointment, nitroglycerin ointment and
      botulinum toxin A. Significant improvement or disappearance of complaints was
      noted in 84% of patients. The use of botulinum toxin A was successfull in 10 out
      of 11 patients without the need of surgical intervention. High efficiency (91% of
      patients) of the sphincter-preserving approach with a significant decrease in the
      need for aggressive surgical manipulation allows to decrease sphincterotomy rate
      and reduces the risk of delayed fecal incontinence.

PMID- 30199056
TI  - [A doctor in social networks: opportunities or limitations?]
AB  - Social media opens great opportunities in doctors' practice, education and
      communication with patients. The information is published easily and instantly,
      just by 'click', but sometimes it's not enough time for the author to think over
      issues of ethics, compliance with the professional standard, the validity of
      statements and their reliability. On the other hand, the capabilities of the
      Internet can detect any publication even after its removal. Currently there are
      no official guidelines regulating the rules of doctor's behavior in social media
      in Russia. In this article we will discuss what to keep in mind while using these
      new opportunities effectively and safely.

PMID- 30199057
TI  - [Common sense of diosmin administration in combined treatment of hemorrhoids].
AB  - Flavonoids are herbal medicines and widely used for chronic venous diseases and
      hemorrhoids. Flavonoid diosmin in both micronized and non-micronized form is a
      part of various drugs. According to literature data, flavonoids are able to
      reduce venous stasis, suppress local inflammation, improve venous tone and
      lymphatic outflow. It should be noted that biological models of in vivo trials
      have certain limitations while available data of different researches are
      contradictory. However, flavonoids were recommended for hemorrhoids in view of
      meta-analysis of 14 trials comparing flavonoids (diosmin, micronized purified
      flavonoid fraction and rutosides) with placebo in 1514 patients with hemorrhoids
      and Cochrane review of 24 randomized controlled trials (2,334 participants).
      These drugs should be administered as a part of complex therapy. At the same
      time, there is no conclusive evidence to prefer only one of these medicines.
      There are also no data confirming the benefits of daily dosage of 3000 mg per day
      of micronized fraction of flavonoids compared with 1800 mg of purified diosmin
      per day for treatment of acute hemorrhoids.

PMID- 30199058
TI  - [Possibilities of thermographic rating the level of microcirculation with local
      anesthesia in dentistry].
AB  - : It is known that the reduction of blood vessels by epinephrine that are part of
      the local anesthetic leads to a decrease in oxygen intake and the development of
      hypoxia, which has a significant effect on the excitability of nerve fibers. This
      is due to the fact that epinephrine is present in the local anesthetic cartridge,
      which helps to reduce, until termination, microcirculation in the depot area,
      which leads to local hypothermia. With the introduction of local anesthetics, the
      temperature of which is significantly lower than the depot temperature, the
      patient experiences severe discomfort, which is associated with unsuccessful
      local anesthesia. The goal of the study was the need to analyze the feasibility
      of using the thermography method in assessing the degree of ischemia of the soft
      tissues of the maxillofacial region against the background of local anesthesia
      with a different concentration of epinephrine in dentistry. MATERIAL AND METHODS:
      In the pilot study, 22 healthy volunteers aged between 29-35 years of both sexes
      participated. To assess the degree of external vasoconstriction, a buccal region
      was chosen near the maxilla. Infiltration anesthesia was used with a 4% solution
      of articaine with epinephrine 1: 100 000 and 1: 200 000 at a dosage of 0.5-0.7
      ml. The temperature distribution in the study area was estimated using a thermal
      imager Nec InfReC Thermo Gear G30. RESULTS: The study showed that the use of
      epinephrine in local anesthetics naturally has a moderate effect on hemodynamics
      in areas adjacent to the anesthesia depot. When using a low concentration of
      epinephrine (1:200 000), the projection hyperthermia of the skin is determined.
      Perhaps this is due to the activation of microcirculation due to an increase in
      capillary blood flow in the region above the zone of action of the epinephrine.
      From the point of view of physiological arterial hyperemia, this mechanism
      carries positive properties, since leads to an increase in tissue oxygenation.
      When using a high concentration of epinephrine (1:100 000), the zone of
      hypothermia of the skin is determined, which corresponds to the phenomenon of
      angiospastic ischemia.

PMID- 30199059
TI  - [The in vitro examination of the effectiveness of antiseptic substances for a
      surface disinfection of teeth inoculated with Escherichia coli].
AB  - The aim of the study was to assess the possibility of penetration of Escherichia
      coli bacteria into the dentinal tubules of the samples and determine the
      antimicrobial efficacy after 5 and 20 min exposition of 3% H2O2 (groups I and II)
      and 1 and 5 min exposition of 3% NaOCl (groups III and IV) for surface
      disinfection of bovine teeth. The samples were subjected to inoculation with E.
      coli suspension. The quality of disinfection was assessed with the three methods.
      The surface disinfection of samples proved to be effective only in groups II and
      IV. In the cultures of all dissolutions of dentinal chips suspensions in groups
      I, III and V there was a growth of E. coli in the form of a continuous pitch. In
      the group II a growth of Escherichia coli was revealed only in the initial
      dissolution in the quantity 1,8x101 CFU/ml, whereas in the group IV the growth
      was nil. Quantitative estimation of bacterial penetration using the method of
      maximum dissolutions revealed similar quantity of bacteria as in the group II as
      well as in the calculation of CFU. The application of 3% solution of H2O2 with
      the exposition of 20 minutes secures the qualitative surface disinfection of
      teeth without destruction of bacteria inside dental tubules and that allows to
      discover viable bacteria inside dentinal tubules.

PMID- 30199060
TI  - [Legislative and regulatory framework of medical products circulation].
AB  - An important task of modern public health is improvement of quality of rendering
      of medical aid to the population. Means for its support at all stages of the
      serve of a medical device (instruments, apparatus, materials, etc.), quality,
      safety and efficacy which play a key role to maintain and improve the quality of
      life of the population.

PMID- 30199061
TI  - [Complex treatment of recurrent herpetic stomatitis in employees of industrial
      enterprises].
AB  - Research ebjective was to study assessment of quality organization of work
      treatment recurrent herpetic stomatitis in patients of industrial enterprises
      from employees.172 patients on the industrial enterprises from 25 to 54 year were
      treated recurrent herpetic stomatitis. Clinical efficiency of immunomodulator
      quality therapy of recurrent herpetic stomatitis for assessment organization of
      work in employees industrial is proved by estimation of oral cavity local
      immunity (SIgA, lisozyme). After treatment of recurrent herpetic stomatitis in
      employees signifie and (p<0,005) inerease of lisozyme and SIgA. The obtaiquality
      of treatment of recurrent herpetic stomatitis et employees of industrial
      enterprises.

PMID- 30199062
TI  - [Incidence and risk factors of oral diseases in pregnant women].
AB  - The prevalence of tooth caries and periodontitis in pregnant women has been
      studied; susceptibility of pregnant women to a high risk of development of dental
      pathology. Proven factors that modify the risk of tooth caries, periodontitis of
      mild and moderate severity in pregnancy are age over 30 years, repeated
      childbirth and pregnancy, complications of the gestational period, and for
      periodontitis, additionally - diseases of the digestive system, musculoskeletal
      system , anemia and metabolic-endocrine disorders.

PMID- 30199063
TI  - [Efficiency of paste and suspension with nano-hydroxyapatite on the sensitivity
      of teeth with gingival recession].
AB  - The purpose of our study was to assess the efficiency of toothpaste 'Intensive
      strengthening of supersensitive teeth with nano-GAP' INNOVA and the suspension
      'Liquid Enamel' INNOVA on the sensitivity of teeth with gingival recession. We
      examined 40 people aged 20-25 years. Each group consisted of 20 people: 10 women,
      10 men. The first group (observations) used the paste and the suspension for 14
      days, and the second group (comparisons) cleaned teeth only with a brush without
      a paste. Schiff aerial test was performed to assess the rate of hypersensitivity.
      As a result of the study, it was found that the combination of paste and liquid
      suspension with nano-hydroxyapatite for 14 days effectively reduced the
      hypersensitivity of the teeth with gingival recession that was shown by a
      statistically significant decrease in the Schiff index in the observation group.
      Thus, this combination is the method of choice in the treatment of hyperesthesia
      and can be used as an alternative substitute therapy.

PMID- 30199064
TI  - [Silentscope - new method of diagnosis and treatment of patients with salivary
      stone disease. The border need to use].
AB  - The authors conducted an analysis of the efficiency of the method of suandokmai
      for diagnosis and treatment of diseases of the salivary glands. The use of
      calendarscope allows to establish the absence of stone in the case of salivary
      colic. In rare cases it is possible to remove the stone without surgical
      intervention at small dimensions of the calculus. 'Price of equipment - the
      efficiency of diagnosis and treatment' does not allow to recommend the method in
      clinical practice.

PMID- 30199065
TI  - [The precision of central jaw relationship estimation in restorative dentistry].
AB  - The aim of the study was to investigate accuracy of the most frequently used
      methods of obtaining centric relation in clinical practice. Finding of CR was
      carried out in clinic of prosthodontic dentistry on a 5 patients with intact
      dentition using four methods that are most often used, including: bimanual
      manipulation, leaf gauge, using an anterior deprogrammind device, the technique
      of determining CR with intraoral devices recording the gothic angle. To assess
      the accuracy of each technique there were performed 10 registrations of the
      central relation by one operator (200 CR registrations), with 30 minutes'
      intervals between the CA determination. Analysis of the contacts in CR were
      carried out using a photometric method of investigation. The graphic images were
      downloaded in Adobe Photoshop for calculation, metric data translated into
      digital values. The studies above showed that the accuracy of finding CR in all
      methods were not ideal. It can be noted that the smallest deviation of the
      position of the first contact in the CR was observed with use of the anterior
      deprogrammind device and with the intoral gothic angle recording device. The
      deviation along the VO axis was 0.039+/-0.002 mm and 0.084+/-0.004 mm
      respectively, along the MD axis 0.043+/-0.002 mm and 0.054+/-0.001 mm,
      respectively. The greatest error of recording the CR was shown by bimanual
      manipulation Dawson technique, the deviation along the axis of the VO and MD was
      0.634+/-0.04 mm and 0.388+/-0.04 mm, respectively.

PMID- 30199066
TI  - [The mesialization of molars of the lower jaw after performance surgical
      manipulation with using miniscrew anchorage approach].
AB  - : Process of the mesialization of molars in the lower jaw is long-time, moreover
      the molars are not frequently bodily translation. Conduction of the corticotomy
      reduce to regional acceleration phenomen that permit to accelerate the tooth
      movement avoiding negative inclination. PURPOSE: To improve the effectiveness of
      the treatment using piezocorticotomy and miniscrew anchorage approach in cases of
      third and second molar mesialization when first molar is missing. MATERIAL AND
      METHODS: 24 patients (10 men/14 women) aged 25-40 years with a fixed vestibular
      braces and the absence of molars on the lower jaw. Cone-beam computed tomography
      was performed before and after orthodontic treatment, as well as immediately
      after the piezokortikotomy (79 Cone-beam computed tomography). Miniscrews was
      placed in the area between roots of the first and second premolars (27
      miniscrews) and surgical manipulations was performed using device VarioSurg (NSK,
      Japan). Depending on width of the alveolar ridge piezocorticotomy was performed
      (16 piezocorticotomies) or splitting using piezosurgery approach (11 splitting).
      RESULTS: Mesialization speed of molars in patients with support of
      piezocorticotomy is equal to 1.1+/-0.1 mm/mo that is higher than in patients
      without surgery only with miniscrew approach (0.33+/-0.006 mm/mo Roberts et al,
      1996). Mesialization speed of molars in patients with support of splitting is
      equal to 1.6+/-0.15 mm/mo. However, we observed that after corticotomies surgery,
      the speed was increased only within the first 4.5 months, after splitting, the
      speed was increased only withing 2.5 months, after that period the speed
      gradually decreases. Bone density after surgery decreased, but at the end of
      treatment gradually restored. CONCLUSION: Piezo surgery with corticotomies is an
      effective method to accelerate the mesialization of molars in the lower jaw, that
      conduce to reduction duration the treatement and to allow to almost bodily
      translation of the molars.

PMID- 30199067
TI  - [A regularity changes occlusal plane inclination in the case of treatment of
      distocclusion by fixed individual lingual appliance].
AB  - : The use of the lingual individual orthodontic appliance is accompanied by
      prematurity contact of the front teeth, which affects the rotation of the
      occlusal plane, especially in cases with distocclusion and deep overbite. The
      study of regularities of changes in the inclination of the occlusal plane is an
      important diagnostic feature, contributes to treatment planning and obtaining
      sustainable results. AIM: To assess the direction of rotation and the degree of
      change in inclination of the occlusal plane in cases with distocclusion. MATERIAL
      AND METHODS: The study included 56 patients, of which 44 were female and 12 were
      male, with distal occlusion of the dentition and deep overbite. We studied the
      position of the occlusal plane, relative to the geometric center of the Ramus -
      point Xi in two groups of patients: 50% with occlusal Biteplanes and 50% without
      occlusal Biteplanes in the upper canine's brackets. RESULTS: In both groups, the
      position of the occlusal plane, relative to the point Xi, has improved: in the
      first - by 1.2 mm, the second - by 2.4 mm. CONCLUSION: The comparison of the
      dataset shows automatical improving of position of the occlusal plane in both
      groups. The most pronounced changes, detected in the treatment with lingual
      braces, shows Biteplane group.

PMID- 30199068
TI  - [Comparative clinical and laboratory study of the force loss generated by NiTi
      closed coil springs].
AB  - The purpose in this study was to compare the force decay of laboratory and
      clinical NiTi closed coil springs. Specimens were 30 NiTi coil springs (clinical)
      and 15 (laboratory in artificial saliva 36.6 oC) springs were tested by
      dynamometer to evaluate force loos at different intervals: 1, 2 and 3 months of
      use. Data (gF) were analyzed statistically using. Clinical and laboratory data
      were compared to evaluate effect of the oral environment on force loss. It was
      observed a significant force loss of NiTi springs. NiTi springs showed force loss
      (13.2%) at 28 days of clinical use, with a further significant loss from 4-12
      weeks (~21%); force levels remained steady thereafter. Were not statistically
      different in clinical and laboratory force loss data. Space was closed at an
      average rate of 1 mm/month.

PMID- 30199069
TI  - [Pulp revascularization for the management of avulsed incisors with immature
      roots and pulp necrosis].
AB  - The aim of the study was to assess the efficacy of pulp revascularization (PR) in
      children with pulp necrosis in immature roots incisors with the history of
      avulsion. The study group comprised 11 children (4 girls and 7 boys aged 86-133
      months) with 13 traumatized incisors with pulp necrosis. Mean age at the time of
      injury was 98.0 months. In 5 children pulp necrosis was associated with extensive
      periapical lesion (PL, 5-26 mm diameter), 4 children with the history of
      inadequate or ineffective endodontic treatment had radiological signs of external
      root resorption. PR was performed according to standard protocol and the results
      were assessed 3, 6, 12, 18 and 24 months after the procedure. All 13 teeth were
      clinically asymptomatic 24 months after PR, but continuous root growth and/or
      apexification was seen in 9 teeth only. PL resolved in all cases, root
      apexification correlated positively with the absence of PL and external root
      resorption, continuous root growth and dentinal walls thickening were less
      evident in patients with pulp necrosis at earlier stages of root development. No
      progression of external root resorption was observed. PR is a useful tool for the
      treatment of immature root incisors with pulp necrosis after teeth avulsion but
      extensive PL and external root resorption prevent adequate apexification probably
      because of the apical papilla necrosis.

PMID- 30199070
TI  - [The need of children of the Crimean regions with different medical and social
      conditions in orthodontic treatment].
AB  - The aim of the study was to investigate the needs of children of various Crimean
      regions in orthodontic care. The epidemiological survey involved 125 children
      under the age of 12 years old living in the regions of Crimea with different
      levels of medical and social conditions (Alushta, Simferopol, Lenin and the
      Krasnogvardeisky district). The two-component IOTN index was used in
      investigation. Children of regional municipal areas showed higher severity of
      malocclusion and the need in orthodontic care than their urban peers (p<0.01 for
      Pearson chi2 criterion). A large part of the surveyed demonstrated a low
      motivation to receive orthodontic treatment according to aesthetic component of
      IOTN index. It was determined a strong correlation between of dental status
      values of the IOTN index and the number of orthodontists in the region, as well
      as the average strength of connection between the objective component of the
      index and ecological potential of the territory. It was revealed a moderate
      linkage between the indicators of the subjective component and the region of
      residence of the child. Thus, it is necessary to develop and implement programs
      of prevention of dentofacial anomalies in children with regard for regional
      peculiarities.

PMID- 30199071
TI  - [Early orthodontic treatment of the patients with Class III malocclusion combined
      with the arches discrepancies using the own design appliance. Clinical case].
AB  - A 6-year-old boy with a skeletal Class III malocclusion was treated with the use
      of the fixed own design orthodontic appliance. The device includes acrylic-splint
      with a three-sided (Bertoni) screw mounted in them, an arc element in the region
      of the front teeth for protractive action on them, metal hooks for the face mask.
      Orthodontic treatment using that appliance allowed to normalize the upper dental
      arche in the sagittal and transversal directions. Thus, conditions for normal
      growth and development of the dentofacial complex were created, which is the main
      goal of early orthodontic intervention.

PMID- 30199072
TI  - [The use of hybrid CAD/CAM materials for rehabilitation of patients with dental
      hard tissues defects].
AB  - The article presents a clinical case demonstrating the effectiveness of hybrid
      materials for rehabilitation of patients with dental hard tissues defects. The
      patient presented with insufficient restoration of teeth 1.3, which was replaced
      by hybrid material Lava Ultimate fixed with adhesive protocol. The use of hybrid
      material allowed minimally invasive preparation of dental hard tissues and
      perfect marginal fit, as well as prevented the attrition of antagonists. The
      important issue in oral rehabilitation with hybrid materials is to respect
      adhesion protocol details.

PMID- 30199073
TI  - [Current trends of the choice and processing of materials for dental
      implantation].
AB  - For assessment of the modern situation about the choice of materials for
      manufacture of dental implants and the processing of their surface the scientific
      literature for the last 2 years was study. On the basis of a large number of
      contradictory results of the researches devoted to each of dental implantation
      problems it is possible to draw a conclusion that any of primal problems of
      implantology is finally not solved. There is no unique opinion at the choice of
      optimum material for manufacture of dental implants, at the way of processing and
      modification of their surface. The problem of improvement of quality of dental
      implantation and fight against complications of this procedure cannot be solved
      simple drawing other substances on the implanted material surface, this task more
      easily and more successfully is solved via changes of product structure and
      various modification of implant surface. Up to the present the researches of an
      opportunity to influence on characteristics of the implanted materials, changing
      their structure and character of a surface, continue. And the publications
      reporting about the considerable positive effect of artificially created
      roughnesses on product surfaces, and the articles claiming that there are no big
      differences between the rough and polished implants are confirmed by objective
      measurements with statistical processing of the obtained data. It should be noted
      that among articles there are very many works of the doubtful plan or with
      insufficiently valid conclusions. This review leads to the conclusion that
      further clinical and experimental studies and about the choice of materials for
      manufacture of implants and at the ways of processing of their surface are
      necessary.

PMID- 30199074
TI  - [Clinical characteristic of factors and tools influencing the effectiveness and
      safety of local anesthesia in dentistry].
AB  - Dental health is one of the most important signs of life quality and depends on
      the level of health care organization. Recently the clinical odontology is
      intensively developing, including local anesthesia where constant searching of
      effective remedies and methods of suppression and treatment of pain is carried
      out. At the same time carrying out adequate local anesthesia has important
      practical value that is to some extent bound to massive visits of the patients to
      the clinics. One of the important factors in the solution of problems of
      effectiveness and safety of local anesthesia is knowledge of anatomy
      topographical features of the structure of maxillofacial area as the irregular
      technique of local anesthesia which is carried out without features of the
      anatomical structure of jaws is the main reason for ineffective anesthesia. From
      the practical side, the special attention is paid to the patients having various
      accompanying diseases with negative treatment emotions that lead to the stress
      development, disorganization of work of functional systems of the organism,
      change of the mental state. However the basis of diagnostic process at dentist's
      consultation depends on the clinical thinking of the doctor which is bound to
      knowledge of medical psychology and psychoprophylaxis that needs to be applied in
      the daily practice. In particular clinical situations premedication methods are
      successfully used for carrying out adequate anesthesia for dental interventions.
      A wide range of ways and methods of the lower alveolar nerve blockade are used in
      dentistry, where the composite external and internal anatomy-topographical
      markers which are difficult to remember for the doctor are applied. It causes the
      need of carrying out further researches on the maximal simplification of
      technological and methodological features of mandibular anesthesia and its
      introduction into dental practice.

PMID- 30199075
TI  - [Problems of education in foreign university dental clinics].

PMID- 30199077
TI  - Findings of Research Misconduct.

PMID- 30199079
TI  - Iron and nitrogen cycling, bacterioplankton community composition and mineral
      transformations involving phosphorus stabilisation in the ferruginous hypolimnion
      of a post-mining lake.
AB  - Lake Medard is an oligotrophic post-mining lake characterised by ferruginous
      bottom waters, with marked redox gradients resulting from iron (Fe) and nitrogen
      (N) speciation and accompanying depth-dependent variations in the abundance of
      volatile fatty acids (VFAs), pH and alkalinity. The lacustrine system is
      meromictic, featuring a dysoxic hypolimnion and an anoxic monimolimnion with
      relatively high concentrations of sulfate (SO42-, 19 +/- 2 mM) and Fe(ii) (127 +/
      17 MUM). An increase in dissolved manganese is also observed with increasing
      depth, together with a general lack of sulfide, which can only be detected at the
      sediment-water interface at concentrations of ~0.30 MUM. In the hypolimnion,
      nitrate (NO3-) becomes progressively depleted and ammonium (NH4+) dominates the
      dissolved N inventory (up to 185 +/- 13 MUM). Here we describe the biogeochemical
      disequilibrium conditions governing critical mineralogical transformations
      involving Fe and phosphorus (P) co-precipitation in the dysoxic-to-anoxic bottom
      water column. A combination of mineral equilibrium modelling and synchrotron
      based diffraction and spectroscopic techniques was applied to investigate the
      minerals comprising the upper anoxic sediments. The combined dataset indicates
      that elemental recycling on and below the hypolimnion promote the precipitation
      of FeOOH polymorphs that accumulate as heterogeneous mineral clusters. Changes in
      the relative abundance of bacterioplankton taxa with increasing water depth point
      to a link between the activity of certain members of Proteobacteria and the co
      recycling of carbon (C), N, and Fe stocks. Such a redox recycling process seems
      to lead to P stabilisation into organic-rich Fe-(oxyhydr)oxides near and above
      the anoxic sediment-water interface (SWI).

PMID- 30199078
TI  - Ultra-high throughput functional enrichment of large monoamine oxidase (MAO-N)
      libraries by fluorescence activated cell sorting.
AB  - Directed evolution enables the improvement and optimisation of enzymes for
      particular applications and is a valuable tool for biotechnology and synthetic
      biology. However, studies are often limited in their scope by the inability to
      screen very large numbers of variants to identify improved enzymes. One class of
      enzyme for which a universal, operationally simple ultra-high throughput (>106
      variants per day) assay is not available is flavin adenine dinucleotide (FAD)
      dependent oxidases. The current high throughput assay involves a visual,
      colourimetric, colony-based screen, however this is not suitable for very large
      libraries and does not enable quantification of the relative fitness of variants.
      To address this, we describe an optimised method for the sensitive detection of
      oxidase activity within single Escherichia coli (E. coli) cells, using the
      monoamine oxidase from Aspergillus niger, MAO-N, as a model system. In contrast
      to other methods for the screening of oxidase activity in vivo, this method does
      not require cell surface expression, emulsion formation or the addition of an
      extracellular peroxidase. Furthermore, we show that fluorescence activated cell
      sorting (FACS) of large libraries derived from MAO-N under the assay conditions
      can enrich the library in functional variants at much higher rates than via the
      colony-based method. We demonstrate its use for directed evolution by identifying
      a new mutant of MAO-N with improved activity towards a novel secondary amine
      substrate. This work demonstrates, for the first time, an ultra-high throughput
      screening methodology widely applicable for the directed evolution of FAD
      dependent oxidases in E. coli.

PMID- 30199080
TI  - Organocatalytic decarboxylative alkylation of N-hydroxy-phthalimide esters
      enabled by pyridine-boryl radicals.
AB  - The decarboxylative alkylation of N-hydroxyphthalimide (NHPI) based reactive
      esters with olefins has been achieved via an organocatalytic strategy. Control
      experiments and density functional theory calculations suggest that these
      reactions involve a boryl-radical mediated decarboxylation pathway, which is
      different from the single electron transfer involved in decarboxylative
      alkylation reactions reported previously. This metal-free decarboxylative
      alkylation reaction features good functional compatibility, and broad substrate
      scope illustrated by the transformations of both the alkyl and aryl carboxylic
      acid derivatives.

PMID- 30199076
TI  - Mood variations decoded from multi-site intracranial human brain activity.
AB  - The ability to decode mood state over time from neural activity could enable
      closed-loop systems to treat neuropsychiatric disorders. However, this decoding
      has not been demonstrated, partly owing to the difficulty of modeling distributed
      mood-relevant neural dynamics while dealing with the sparsity of mood state
      measurements. Here we develop a modeling framework to decode mood state
      variations from multi-site intracranial recordings in seven human subjects with
      epilepsy who self-reported their mood state intermittently over multiple days. We
      built dynamic neural encoding models of mood state and corresponding decoders for
      each individual and demonstrated that mood state variations over time can be
      decoded from neural activity. Across subjects, the decoders largely recruited
      neural signals from limbic regions, whose spectro-spatial features were tuned to
      mood variations. The dynamic models also provided an analytical tool to compute
      the timescales of the decoded mood state. These results provide an initial line
      of evidence indicating the feasibility of mood state decoding.

PMID- 30199081
TI  - Morphology led high dispersion of Pt icosahedral nanocrystals on carbon nanotubes
      for enhanced electro-catalytic activity and stability.
AB  - Icosahedra have small contact areas during packing, leading small icosahedral Pt
      nanoparticles to highly disperse on carbon nanotubes (CNT). The as-synthesized
      highly monodispersed Pt icosahedra on CNT exhibited superior catalytic activity
      and structural stability to their Pt nanocube counterparts on CNT towards
      methanol electro-oxidation.

PMID- 30199082
TI  - Chiral halogen and chalcogen bonding receptors for discrimination of stereo- and
      geometric dicarboxylate isomers in aqueous media.
AB  - Novel chiral halogen and chalcogen bonding receptors exhibit different
      selectivities for stereo- and geometric dicarboxylate isomers compared to a
      hydrogen bonding analogue. The unique geometric and electronic properties of the
      chalcogen bonding receptor facilitate the diagnostic fluorescence sensing of
      geometric dicarboxylate isomer guest species.

PMID- 30199083
TI  - Determination of the local structure of Sr2-xMxIrO4 (M = K, La) as a function of
      doping and temperature.
AB  - The local structure of correlated spin-orbit insulator Sr2-xMxIrO4 (M = K, La)
      has been investigated by Ir L3-edge extended X-ray absorption fine structure
      measurements. The measurements were performed as a function of temperature for
      different dopings induced by substitution of Sr with La or K. It is found that Ir
      O bonds have strong covalency and they hardly show any change across the Neel
      temperature. In the studied doping range, neither Ir-O bonds nor their dynamics,
      measured by their mean square relative displacements, show any appreciable change
      upon carrier doping, indicating the possibility of nanoscale phase separation in
      the doped system. On the other hand, there is a large increase of the static
      disorder in Ir-Sr correlation, larger for K doping than La doping. Similarities
      and differences with respect to the local lattice displacements in cuprates are
      briefly discussed.

PMID- 30199084
TI  - Plasmonic zero mode waveguide for highly confined and enhanced fluorescence
      emission.
AB  - We fabricate a plasmonic nanoslot that is capable of performing enhanced single
      molecule detection at 10 MUM concentrations. The nanoslot combines the tiny
      detection volume of a zero-mode waveguide and the field enhancement of a
      plasmonic nanohole. The nanoslot is fabricated on a bi-metallic film formed by
      the sequential deposition of gold and aluminum on a transparent substrate.
      Simulations of the structure yield an average near-field intensity enhancement of
      two orders of magnitude at its resonant frequency. Experimentally, we measure the
      fluorescence stemming from the nanoslot and compare it with that of a standard
      aluminum zero-mode waveguide. We also compare the detection volume for both
      structures. We observe that while both structures have a similar detection
      volume, the nanoslot yields a 25-fold fluorescence enhancement.

PMID- 30199085
TI  - Bi-directional relation between effort-reward imbalance and risk of neck-shoulder
      pain: assessment of mediation through depressive symptoms using occupational
      longitudinal data.
AB  - Objectives Bi-directional associations between perceived effort-reward imbalance
      (ERI) at work and neck-shoulder pain have been reported. There is also evidence
      of associations between ERI and depressive symptoms, and between depressive
      symptoms and pain while the links between ERI, depressive symptoms and pain have
      not been tested. We aimed to assess whether depressive symptoms mediate the
      association between ERI and neck-shoulder pain, as well as the association
      between neck-shoulder pain and ERI. Methods We used prospective data from three
      consecutive surveys of the Swedish Longitudinal Occupational Survey of Health
      (SLOSH) study. ERI was assessed with a short version of the ERI questionnaire,
      and pain was defined as having had neck-shoulder pain that affected daily life
      during the past three months. Depressive symptoms were assessed with a continuous
      scale based on six-items of the (Hopkins) Symptom Checklist. Counterfactual
      mediation analyses were applied using exposure measures from 2010/2012 (T1),
      depressive symptoms from 2012/2014 (T2), and outcomes from 2014/2016 (T3), and
      including only those free of outcome at T1 and T2 (N=2876-3239). Results ERI was
      associated with a higher risk of neck-shoulder pain [risk ratio (RR) for total
      effect 1.24, 95% confidence interval (CI) 1.02-1.50] and 40% of this total effect
      was mediated through depressive symptoms. Corresponding RR for association
      between neck-shoulder pain and ERI was 1.36 (95% CI 1.13-1.65), but the mediating
      role of depressive symptoms was less consistent. Conclusions Depressive symptoms
      appear to be an intermediate factor in the relationship between ERI and neck
      shoulder pain.

PMID- 30199086
TI  - Photosynthetic opportunity cost and energetic cost of a rapid leaf closure
      behavior in Mimosa pudica.
AB  - PREMISE OF THE STUDY: The rapid leaf movement of Mimosa pudica is expected to be
      costly because of energetic trade-offs with other processes such as growth and
      reproduction. Here, we assess the photosynthetic opportunity cost and energetic
      cost of the unique leaf closing behavior of M. pudica. METHODS: In the
      greenhouse, we employed novel touch-stimulation machines to expose plants to one
      of three treatments: (1) untouched control plants; (2) plants touch-stimulated to
      close their leaves during the day to incur energetic costs associated with leaf
      movement and reduced photosynthesis; (3) plants touched at night to assess the
      effects of touch alone. M. pudica is nyctinastic and closes its leaves at night;
      thus, touching at night does not impart additional costs. We directly assessed
      costs by comparing physical traits. Leaf re-opening response was measured to
      assess the potential for plant behavioral plasticity to impact photosynthetic
      opportunity costs. KEY RESULTS: The cost of rapid leaf closure behavior was
      expressed as a 47% reduction in reproductive biomass accounting for the effect of
      touch. Touch itself changed physical traits such as biomass, with touched plants
      being generally bigger. Plants touched at night re-opened their leaflets 26%
      quicker than plants touched during the day. CONCLUSIONS: We reason that the
      reproductive allocation costs incurred by M. pudica can be attributed to a
      combination of photosynthetic opportunity cost and the energetic cost associated
      with increased stimulation of leaf movement and that behavioral plasticity has
      the potential to alter photosynthetic opportunity costs.

PMID- 30199088
TI  - "I Wouldn't Ever Want It": A Qualitative Evaluation of Patient and Caregiver
      Perceptions Toward Enteral Tube Feeding in Hip Fracture Inpatients.
AB  - BACKGROUND: One in 2 hip fracture inpatients are malnourished on admission to
      hospital, with many experiencing nutrition decline during their length of stay.
      Despite this, enteral tube feeding (ETF) is rarely used in this population. As
      patient/caregiver viewpoints regarding the utility of ETF remain unclear, this
      study explored the perceptions of hip fracture inpatients and caregivers toward
      ETF use to assist recovery. METHODS: An inductive qualitative research project
      was conducted within a tertiary hospital orthogeriatric ward. Individual
      semistructured interviews were undertaken with 13 purposively sampled,
      postsurgery hip fracture inpatients and 7 caregivers. Interviews were
      transcribed, hard-copy coded, and thematically analyzed. RESULTS: The majority of
      inpatient participants did not wish to be tube fed. A novel, complex
      interrelationship of the following 3 main themes emerged: knowledge and
      understanding, perceived consequences and necessity of tube, contributed toward
      potential ETF acceptance and refusal. Theme interrelationship was indicated by
      subthemes (nutrition importance, attitude, and ability to cope) and driven by the
      following 3 key categories: value of nutrition, quality of life, and personal
      perception. CONCLUSION: A number of factors impacted the likelihood of tube
      acceptance. This highlights the importance of food as a medicine, treatment
      intent, and shared decision making when considering ETF in acute hip fracture
      inpatients.

PMID- 30199087
TI  - Corrigendum.

PMID- 30199089
TI  - Dynamic mass spectrometry probe for electrospray ionization mass spectrometry
      monitoring of bioreactors for therapeutic cell manufacturing.
AB  - Large-scale manufacturing of therapeutic cells requires bioreactor technologies
      with online feedback control enabled by monitoring of secreted biomolecular
      critical quality attributes (CQAs). Electrospray ionization mass spectrometry
      (ESI-MS) is a highly sensitive label-free method to detect and identify
      biomolecules, but requires extensive sample preparation before analysis, making
      online application of ESI-MS challenging. We present a microfabricated,
      monolithically integrated device capable of continuous sample collection,
      treatment, and direct infusion for ESI-MS detection of biomolecules in high-salt
      solutions. The dynamic mass spectrometry probe (DMSP) uses a microfluidic mass
      exchanger to rapidly condition samples for online MS analysis by removing
      interfering salts, while concurrently introducing MS signal enhancers to the
      sample for sensitive biomolecular detection. Exploiting this active conditioning
      capability increases MS signal intensity and signal-to-noise ratio. As a result,
      sensitivity for low-concentration biomolecules is significantly improved, and
      multiple proteins can be detected from chemically complex samples. Thus, the DMSP
      has significant potential to serve as an enabling portion of a novel analytical
      tool for discovery and monitoring of CQAs relevant to therapeutic cell
      manufacturing.

PMID- 30199091
TI  - Fed-batch production of l-tryptophan from glycerol using recombinant Escherichia
      coli.
AB  - l-tryptophan is an essential amino acid of high industrial interest that is
      routinely produced by microbial processes from glucose as carbon source. Glycerol
      is an alternative substrate providing a variety of economic and metabolic
      advantages. Process performance of the recombinant l-tryptophan producer
      Escherichia coli NT367 was studied in controlled fed-batch processes. The
      chromosome of the recombinant l-tryptophan producer was equipped with additional
      genes coding for enzymes of the aromatic amino acids biosynthetic pathway and l
      serine biosynthesis, including genes for feedback-resistant enzyme variants (
      trpE fbr , aroFBL, and serA fbr ), deletions of enzymatic steps for the
      degradation of precursors or the product l-tryptophan ( sdaB and tnaA), and
      alterations in the regulation of l-tryptophan metabolism (deletion of trpL and
      trpR). The impact of glycerol supply rates as well as the application of a
      multicopy plasmid (pF112- aroFBL -kan) were investigated in fully controlled
      stirred-tank bioreactors on a 15 L scale. The combination of E. coli NT367
      carrying pF112- aroFBL -kan and an appropriate biomass-specific glycerol supply
      rate resulted in the highest final product concentration of 12.5 g L -1 l
      tryptophan with the lowest concentrations of other aromatic amino acids. Fed
      batch production of l-tryptophan from glycerol was shown for the first time with
      recombinant E. coli.

PMID- 30199090
TI  - A synthetic enzymatic pathway for extremely thermophilic acetone production based
      on the unexpectedly thermostable acetoacetate decarboxylase from Clostridium
      acetobutylicum.
AB  - One potential advantage of an extremely thermophilic metabolic engineering host
      (T opt >= 70 degrees C) is facilitated recovery of volatile chemicals from the
      vapor phase of an active fermenting culture. This process would reduce
      purification costs and concomitantly alleviate toxicity to the cells by
      continuously removing solvent fermentation products such as acetone or ethanol, a
      process we are calling "bio-reactive distillation." Although extremely
      thermophilic heterologous metabolic pathways can be inspired by existing
      mesophilic versions, they require thermostable homologs of the constituent
      enzymes if they are to be utilized in extremely thermophilic bacteria or archaea.
      Production of acetone from acetyl-CoA and acetate in the mesophilic bacterium
      Clostridium acetobutylicum utilizes three enzymes: thiolase, acetoacetyl-CoA:
      acetate CoA transferase (CtfAB), and acetoacetate decarboxylase (Adc). Previously
      reported biocatalytic pathways for acetone production were demonstrated only as
      high as 55 degrees C. Here, we demonstrate a synthetic enzymatic pathway for
      acetone production that functions up to at least 70 degrees C in vitro, made
      possible by the unusual thermostability of Adc from the mesophile C.
      acetobutylicum, and heteromultimeric acetoacetyl-CoA:acetate CoA-transferase
      (CtfAB) complexes from Thermosipho melanesiensis and Caldanaerobacter
      subterraneus, composed of a highly thermostable alpha-subunit and a thermally
      labile beta-subunit. The three enzymes produce acetone in vitro at temperatures
      of at least 70 degrees C, paving the way for bio-reactive distillation of acetone
      using a metabolically engineered extreme thermophile as a production host.

PMID- 30199092
TI  - Seasonal influenza activity based on laboratory surveillance in Malaysia, 2011
      2016.
AB  - Influenza seasonality in equatorial countries is little understood. Seasonal and
      alert influenza thresholds were determined for Malaysia, using laboratory-based
      data obtained from the Malaysia Influenza Surveillance System and a major
      teaching hospital, from 2011 to 2016. Influenza was present year-round, with no
      clear annual seasons. Variable periods of higher transmission occurred
      inconsistently, in November to December, January to March, July to September, or
      a combination of these. These coincide with seasons in the nearby southeast Asian
      countries or winter seasons of the northern and southern hemispheres. Changes in
      the predominant circulating influenza type were only sometimes associated with
      increased transmission. The data can provide public health interventions such as
      vaccines.

PMID- 30199093
TI  - Network meta-analysis of topical haemostatic agents in thyroid surgery.
AB  - BACKGROUND: The objective of this study was to investigate the potential benefit
      of local haemostatic agents for the prevention of postoperative bleeding after
      thyroidectomy. METHODS: A systematic literature search was performed, and RCTs
      involving adult patients who underwent thyroid surgery using either active (AHA)
      or passive (PHA) haemostatic agents were included in the review. The main outcome
      was the rate of cervical haematoma that required reoperation. A Bayesian random
      effects model was used for network meta-analysis with minimally informative prior
      distributions. RESULTS: Thirteen RCTs were included. The rate of cervical
      haematoma requiring reoperation ranged from 0 to 9.1 per cent, and was not
      reduced by haemostatic agents: AHA versus control (odds ratio (OR) 1.53, 95 per
      cent credibility interval 0.21 to 10.77); PHA versus control (OR 2.74, 0.41 to
      16.62) and AHA versus PHA (OR 1.77, 0.12 to 25.06). No difference was observed in
      the time required for drain removal, duration of hospital stay, and the rate of
      postoperative hypocalcaemia or recurrent nerve palsy. AHA led to a significantly
      lower total postoperative blood loss and reduced operating time in comparison
      with both the control and PHA groups. CONCLUSION: The general use of local
      haemostatic agents has not been shown to reduce the rate of clinically relevant
      bleeding.

PMID- 30199094
TI  - Unraveling the genetic basis of fast l-arabinose consumption on top of
      recombinant xylose-fermenting Saccharomyces cerevisiae.
AB  - One major challenge in the bioconversion of lignocelluloses into ethanol is to
      develop Saccharomyces cerevisiae strains that can utilize all available sugars in
      biomass hydrolysates, especially the d-xylose and l-arabinose that cannot be
      fermented by the S. cerevisiae strain naturally. Here, we integrated an l
      arabinose utilization cassette (AUC) into the genome of an efficient d-xylose
      fermenting industrial diploid S. cerevisiae strain CIBTS0735 to make strain
      CIBTS1972. After evolving on arabinose, CIBTS1974 with excellent fermentation
      capacity was obtained. A comparison between genome sequences of strains CIBTS1974
      and CIBTS1972 revealed that the copy number of the AUC had increased from 1 to
      12. We then constructed the AUC null-mutant CIBTS1975 and gradually rescued the l
      arabinose utilization defect by integrating AUC iteratively. On the other hand,
      the parental strain CIBTS0735 was able to acquire the same performance as
      CIBTS1974 by the direct introduction of 12 copies of the AUC; the performance was
      further improved by adding two more copies. Besides, we found that not the two
      transporters present in the AUC were both needed during l-arabinose utilization,
      GAL2 was necessary and STP2 was not essential. We have described for the first
      time that a high copy number of AUC is sufficient for the strain to metabolize l
      arabinose efficiently independent of evolution.

PMID- 30199095
TI  - Growth hormone secretagogue receptor constitutive activity impairs voltage-gated
      calcium channel-dependent inhibitory neurotransmission in hippocampal neurons.
AB  - KEY POINTS: Presynaptic CaV 2 voltage-gated calcium channels link action
      potentials arriving at the presynaptic terminal to neurotransmitter release.
      Hence, their regulation is essential to fine tune brain circuitry. CaV 2 channels
      are highly sensitive to G protein-coupled receptor (GPCR) modulation. Our
      previous data indicated that growth hormone secretagogue receptor (GHSR)
      constitutive activity impairs CaV 2 channels by decreasing their surface density.
      We present compelling support for the impact of CaV 2.2 channel inhibition by
      agonist-independent GHSR activity exclusively on GABA release in hippocampal
      cultures. We found that this selectivity arises from a high reliance of GABA
      release on CaV 2.2 rather than on CaV 2.1 channels. Our data provide new
      information on the effects of the ghrelin-GHSR system on synaptic transmission,
      suggesting a putative physiological role of the constitutive signalling of a GPCR
      that is expressed at high levels in brain areas with restricted access to its
      natural agonist. ABSTRACT: Growth hormone secretagogue receptor (GHSR) displays
      high constitutive activity, independent of its endogenous ligand, ghrelin. Unlike
      ghrelin-induced GHSR activity, the physiological role of GHSR constitutive
      activity and the mechanisms that underlie GHSR neuronal modulation remain
      elusive. We previously demonstrated that GHSR constitutive activity modulates
      presynaptic CaV 2 voltage-gated calcium channels. Here we postulate that GHSR
      constitutive activity-mediated modulation of CaV 2 channels could be relevant in
      the hippocampus since this brain area has high GHSR expression but restricted
      access to ghrelin. We performed whole-cell patch-clamp in hippocampal primary
      cultures from E16- to E18-day-old C57BL6 wild-type and GHSR-deficient mice after
      manipulating GHSR expression with lentiviral transduction. We found that GHSR
      constitutive activity impairs CaV 2.1 and CaV 2.2 native calcium currents and
      that CaV 2.2 basal impairment leads to a decrease in GABA but not glutamate
      release. We postulated that this selective effect is related to a higher CaV 2.2
      over CaV 2.1 contribution to GABA release (~40% for CaV 2.2 in wild-type vs. ~20%
      in wild-type GHSR-overexpressing cultures). This effect of GHSR constitutive
      activity is conserved in hippocampal brain slices, where GHSR constitutive
      activity reduces local GABAergic transmission of the granule cell layer (intra
      granule cell inhibitory postsynaptic current (IPSC) size ~-67 pA in wild-type vs.
      ~-100 pA in GHSR-deficient mice), whereas the glutamatergic output from the
      dentate gyrus to CA3 remains unchanged. In summary, we found that GHSR
      constitutive activity impairs IPSCs both in hippocampal primary cultures and in
      brain slices through a CaV 2-dependent mechanism without affecting glutamatergic
      transmission.

PMID- 30199097
TI  - Antigen-specific active immunotherapy for ovarian cancer.
AB  - BACKGROUND: This is the second update of the review first published in the
      Cochrane Library (2010, Issue 2) and later updated (2014, Issue 9).Despite
      advances in chemotherapy, the prognosis of ovarian cancer remains poor. Antigen
      specific active immunotherapy aims to induce tumour antigen-specific anti-tumour
      immune responses as an alternative treatment for ovarian cancer. OBJECTIVES:
      Primary objective* To assess the clinical efficacy of antigen-specific active
      immunotherapy for the treatment of ovarian cancer as evaluated by tumour response
      measured by Response Evaluation Criteria In Solid Tumors (RECIST) and/or cancer
      antigen (CA)-125 levels, response to post-immunotherapy treatment, and survival
      differences? In addition, we recorded the numbers of observed antigen-specific
      humoral and cellular responsesSecondary objective* To establish which
      combinations of immunotherapeutic strategies with tumour antigens provide the
      best immunological and clinical results SEARCH METHODS: For the previous version
      of this review, we performed a systematic search of the Cochrane Central Register
      of Controlled Trials (CENTRAL; 2009, Issue 3), in the Cochrane Library, the
      Cochrane Gynaecological Cancer Group Specialised Register, MEDLINE and Embase
      databases, and clinicaltrials.gov (1966 to July 2009). We also conducted
      handsearches of the proceedings of relevant annual meetings (1996 to July
      2009).For the first update of this review, we extended the searches to October
      2013, and for this update, we extended the searches to July 2017. SELECTION
      CRITERIA: We searched for randomised controlled trials (RCTs), as well as non
      randomised studies (NRSs), that included participants with epithelial ovarian
      cancer, irrespective of disease stage, who were treated with antigen-specific
      active immunotherapy, irrespective of type of vaccine, antigen used, adjuvant
      used, route of vaccination, treatment schedule, and reported clinical or
      immunological outcomes. DATA COLLECTION AND ANALYSIS: Two reviews authors
      independently extracted the data. We evaluated the risk of bias for RCTs
      according to standard methodological procedures expected by Cochrane, and for
      NRSs by using a selection of quality domains deemed best applicable to the NRS.
      MAIN RESULTS: We included 67 studies (representing 3632 women with epithelial
      ovarian cancer). The most striking observations of this review address the lack
      of uniformity in conduct and reporting of early-phase immunotherapy studies.
      Response definitions show substantial variation between trials, which makes
      comparison of trial results unreliable. Information on adverse events is
      frequently limited. Furthermore, reports of both RCTs and NRSs frequently lack
      the relevant information necessary for risk of bias assessment. Therefore, we
      cannot rule out serious biases in most of the included trials. However,
      selection, attrition, and selective reporting biases are likely to have affected
      the studies included in this review. GRADE ratings were high only for survival;
      for other primary outcomes, GRADE ratings were very low.The largest body of
      evidence is currently available for CA-125-targeted antibody therapy (17 studies,
      2347 participants; very low-certainty evidence). Non-randomised studies of CA-125
      targeted antibody therapy suggest improved survival among humoral and/or cellular
      responders, with only moderate adverse events. However, four large randomised
      placebo-controlled trials did not show any clinical benefit, despite induction of
      immune responses in approximately 60% of participants. Time to relapse with CA
      125 monoclonal antibody versus placebo, respectively, ranged from 10.3 to 18.9
      months versus 10.3 to 13 months (six RCTs, 1882 participants; high-certainty
      evidence). Only one RCT provided data on overall survival, reporting rates of 80%
      in both treatment and placebo groups (three RCTs, 1062 participants; high
      certainty evidence). Other small studies targeting many different tumour antigens
      have presented promising immunological results. As these strategies have not yet
      been tested in RCTs, no reliable inferences about clinical efficacy can be made.
      Given the promising immunological results and the limited side effects and
      toxicity reported, exploration of clinical efficacy in large well-designed RCTs
      may be worthwhile. AUTHORS' CONCLUSIONS: We conclude that despite promising
      immunological responses, no clinically effective antigen-specific active
      immunotherapy is yet available for ovarian cancer. Results should be interpreted
      cautiously, as review authors found a significant dearth of relevant information
      for assessment of risk of bias in both RCTs and NRSs.

PMID- 30199096
TI  - A fully online sensor-equipped, disposable multiphase microbioreactor as a
      screening platform for biotechnological applications.
AB  - A new disposable, multiphase, microbioreactor (MBR; with a working volume of 550
      MUl) equipped with online sensors is presented for biotechnological screening
      research purposes owing to its high-throughput potential. Its design and
      fabrication, online sensor integration, and operation are described. During
      aerobic cultivation, sufficient oxygen supply is the most important factor that
      influences growth and product formation. The MBR is a microbubble column
      bioreactor (MUBC), and the oxygen supply was realized by active pneumatic bubble
      aeration, ensuring sufficient volumetric liquid-phase mass transfer (k L a) and
      proper homogenization of the cultivation broth. The MUBC was equipped with
      miniaturized sensors for the pH, dissolved oxygen, optical density and glucose
      concentration that allowed real-time online monitoring of these process variables
      during cultivation. The challenge addressed here was the integration of sensors
      in the limited available space. The MBR was shown to be a suitable screening
      platform for the cultivation of biological systems. Batch cultivations of
      Saccharomyces cerevisiae were performed to observe the variation in the process
      variables over time and to show the robustness and operability of all the online
      sensors in the MBR.

PMID- 30199098
TI  - HIV Antiretroviral Pre-Exposure Prophylaxis: Development Challenges and Pipeline
      Promise.
AB  - The US Food and Drug Administration (FDA) approved oral daily
      tenofovir/emtricitabine (Truvada) for pre-exposure prophylaxis of human
      immunodeficiency virus (HIV) infection in 2012 on the basis of two randomized
      controlled trials (RCTs), one in men who have sex with men (MSM) and another in
      HIV serodiscordant heterosexual couples. Subsequently, even greater efficacy has
      been demonstrated in MSM with rapid population-level incidence reductions in some
      locations. In contrast, studies of antiretroviral pre-exposure prophylaxis (PrEP)
      in heterosexual women showed only modest or no efficacy, largely attributed to
      low adherence. The mixed results of antiretroviral-based PrEP bear witness to
      unique drug development challenges at this complicated intersection of sexual
      behavior, public health, and drug development. Multiple innovative methods and
      formulation strategies followed to address unmet medical needs of persons
      struggling with daily oral PrEP adherence or preference for nonsystemic PrEP
      options. Clinical pharmacology plays essential roles throughout this PrEP
      development process, especially in early product development and through
      pharmacologically informed enhancement and interpretation of clinical trials.

PMID- 30199100
TI  - Multicentre study of the prognostic impact of preoperative bodyweight on long
      term prognosis of hepatocellular carcinoma.
AB  - BACKGROUND: Whether preoperative bodyweight is associated with long-term
      prognosis in patients after liver resection for hepatocellular carcinoma (HCC) is
      controversial. This study aimed to investigate the relationship of patient weight
      with long-term recurrence and overall survival (OS) after curative liver
      resection for HCC. METHODS: Data for patients with HCC who underwent curative
      liver resection between 2000 and 2015 in five centres in China were analysed
      retrospectively in three groups according to their preoperative BMI: underweight
      (BMI 18.4 kg/m2 or less), normal weight (BMI 18.5-24.9 kg/m2 ) and overweight
      (BMI 25.0 kg/m2 or above). Patients' baseline characteristics, operative
      variables and long-term survival outcomes were compared. Univariable and
      multivariable Cox regression analyses were performed to identify risk factors for
      OS and recurrence-free survival (RFS) after resection. RESULTS: Of 1524 patients,
      107 (7.0 per cent) were underweight, 891 (58.5 per cent) were of normal weight
      and 526 (34.5 per cent) were overweight. Univariable analyses showed that
      underweight and overweight patients had poorer OS (both P < 0.001) and RFS (both
      P < 0.001) than patients of normal weight. Multivariable Cox regression analysis
      also identified both underweight and overweight to be independent risk factors
      for OS (hazard ratio (HR) 1.22, 95 per cent c.i. 1.19 to 1.56, P = 0.019; and HR
      1.57, 1.36 to 1.81, P < 0.001, respectively) and RFS (HR 1.28, 1.16 to 1.53, P =
      0.028; and HR 1.34, 1.17 to 1.54, P < 0.001). CONCLUSION: Underweight and
      overweight patients appear to have a worse prognosis than those of normal weight
      following liver resection for HCC.

PMID- 30199099
TI  - Reverse transduction can improve efficiency of AAV vectors in transduction
      resistant cells.
AB  - Reverse transduction, also known as substrate-mediated gene delivery, is a
      strategy in which viral vectors are first coated onto a surface that subsequently
      comes into contact with mammalian cells. The cells internalize the surface
      attached vectors, resulting in transgene expression. We hypothesized that forcing
      the interaction between cells and adeno-associated virus (AAV) vectors through a
      reverse transduction format would increase in vitro gene delivery efficiencies of
      the vectors in transduction-resistant cells. We tested this hypothesis by
      comparing the gene delivery efficiencies of three AAV serotypes using either
      standard or reverse transduction approaches. Our study reveals reverse
      transduction of AAV7 and AAV9 can significantly improve their delivery
      efficiencies. In contrast, AAV2 does not perform better under the reverse
      transduction format. Interestingly, increased vector uptake by cells does not
      provide a complete explanation for the increased transduction efficiency. Our
      findings offer a simple and practical method for improving transduction outcomes
      in vitro in cell types less permissive to a particular AAV vector.

PMID- 30199102
TI  - A method for tumor dosimetry based on hybrid planar-SPECT/CT images and
      semiautomatic segmentation.
AB  - PURPOSE: A hybrid planar-SPECT/CT method for tumor dosimetry in  METHODS: The
      imaging protocol includes conjugate-view imaging at 1, 24, 96, and 168 h post
      infusion (p.i.) and a SPECT/CT acquisition 24 h p.i. The dosimetry method uses
      the planar images to estimate the shape of the time-activity concentration curve,
      which is then rescaled to absolute units using the SPECT-derived activity
      concentration. The resulting time-integrated activity concentration coefficient
      (TIACC) is used to calculate the tumor-absorbed dose. Semiautomatic segmentation
      techniques are applied for tumor delineation in both planar and SPECT images,
      where the planar image segmentation is accomplished using an active-rays-based
      technique. The selection of tumors is done by visual inspection of planar and
      SPECT images and applying a set of criteria concerning the tumor visibility and
      possible interference from superimposed activity uptakes in the planar images.
      Five different strategies for determining values from planar regions of interest
      (ROIs), based on entire or partial ROIs, and with and without background
      correction, are evaluated. Evaluation is performed against a SPECT/CT-based
      method on data from six patients where sequential conjugate-view and SPECT/CT
      imaging have been performed in parallel and against ground truths in Monte Carlo
      simulated images. The patient data are also used to evaluate the interoperator
      variability and to assess the validity of the developed criteria for tumor
      selection. RESULTS: For patient images, the hybrid method produces TIACCs that
      are on average 6% below those of the SPECT/CT only method, with standard
      deviations for the relative TIACC differences of 8%-11%. Simulations show that
      the hybrid and SPECT-based methods estimate the TIACCs to within approximately
      10% for tumors larger than around 10 ml, while for smaller tumors, all methods
      underestimate the TIACCs due to underestimations of the activity concentrations
      in the SPECT images. The planar image segmentation has a low operator dependence,
      with a median Dice similarity coefficient of 0.97 between operators. The adopted
      criteria for tumor selection manage to discriminate the tumors for which the
      absorbed-dose deviations between the hybrid and SPECT methods are the highest.
      CONCLUSIONS: The hybrid method is found suitable for studies of tumor-absorbed
      doses in radionuclide therapy, provided that selection criteria regarding the
      visibility and overlapping activities in the planar images are applied.

PMID- 30199101
TI  - ScatterNet: A convolutional neural network for cone-beam CT intensity correction.
AB  - PURPOSE: To demonstrate a proof-of-concept for fast cone-beam CT (CBCT) intensity
      correction in projection space by the use of deep learning. METHODS: The CBCT
      scans and corresponding projections were acquired from 30 prostate cancer
      patients. Reference shading correction was performed using a validated method
      (CBCT  RESULTS: The CBCT  CONCLUSIONS: Using a deep convolutional neural network
      for CBCT intensity correction was shown to be feasible in the pelvic region for
      the first time. Dose calculation accuracy on CBCT 

PMID- 30199103
TI  - JPEN Journal Club 38. One-Tailed Testing.

PMID- 30199107
TI  - Editorial.

PMID- 30199106
TI  - The Influence of Ultrasound and Cultivar Selection on the Biocompounds and
      Physicochemical Characteristics of Dried Blueberry (Vaccinium corymbosum L.)
      Snacks.
AB  - : The aim of the study was to characterize physical and chemical composition of
      four highbush blueberry cultivars ("Bluecrop," "Late Blue," "Chandler," and
      "Elliot"). The assessment of ultrasound influence at the osmotic dehydration step
      and during hybrid drying on mass transfer and the nutritional quality of all
      cultivars was also done. The experiment consisted of two stages: (1) initial:
      optimization of osmotic dehydration procedure, (2) the main experiment including
      all stages of dried blueberry production (pretreatment, osmotic dehydration
      chosen in the initial stage, and drying). In both parts, the effect of US and
      cultivar were considered as factors influencing the most important quality
      indices. The osmotic dehydration, in the mixture (1:1) of sucrose solution and
      apple juice concentrate (65 degrees Bx) at a fruit to syrup ratio 1:4, was
      carried out in water bath fitted with ultrasonic transducers (25 kHz, 27.8 W/L)
      at a temperature of 40 degrees C for 150 min. After pretreatment osmo-dehydrated
      fruits were subjected to drying in hybrid (microwave-ultrasound-convective) drum
      dryer. Regardless of the cultivar US had positive influence on mass transfer (up
      to 22% for intact and 12% for mechanically scratched) at the osmotic dehydration
      stage. Unfavorably, its action tend to decrease phenolic compounds content. The
      final effect, however, was strongly influenced by the choice of cultivar. With
      regard to ultrasound applied at the drying step, no explicit effect, either on
      the drying process efficiency or on final product quality, was identified. In the
      same processing conditions "Elliot" turned out to be the most promising to
      produce ready-to-eat fruit snacks in terms of the final product stability and
      bioactives content. PRACTICAL APPLICATION: Hybrid drying was proposed as a novel
      approach in blueberry drying. Ultrasound application as a part of abovementioned
      drying technique is considered an efficient way of shortening drying time due to
      mass transfer intensification and the interaction with dehydrated tissue.
      However, no experiments studying the impact of ultrasound on various cultivars
      within one species were carried out. This study contributes to the understanding
      that appropriate cultivar selection in the production of ready-to-eat dried
      blueberry fruit is just as important as process parameters in obtaining an
      attractive product with a high level of natural bioactive compounds.

PMID- 30199104
TI  - A new sRNA-mediated posttranscriptional regulation system for Bacillus subtilis.
AB  - Many genetic tools for gene regulation have been developed during the past
      decades. Some of them edit genomic DNA, such as nucleotides deletions and
      insertions, while the others interfere with the gene transcriptions or messenger
      RNA translation. Here, we report a posttranscriptional regulation tool which is
      termed "Modulation via the small RNA (sRNA)-dependent operation system: MS-DOS"
      by engineering the type I toxin-antitoxin system in Bacillus subtilis. MS-DOS
      depends simply on insertion of an operation region (OPR; partial toxin-encoding
      region) downstream of a genomic open reading frame of interest and overexpression
      of the coupling antitoxin sRNA from a plasmid. Pairing between the OPR and the
      sRNA will trigger the RNAse degradation of the transcripts of selected genes. MS
      DOS allows for the quantitative, specific, and reversible knockdown of single or
      multiple genomic genes in B. subtilis. We also showed that the truncated
      antitoxin SR4 with 53 nt length is sufficient to repress gene expression.
      Superior to other existing RNA based interfering systems, MS-DOS allows
      simultaneous knockdown of multiple genes with effortless expression of a single
      antitoxin RNA. This sRNA-guided repression system will further enrich the gene
      regulation tools and expand the gene regulation flexibility.

PMID- 30199108
TI  - Two-Dimensional Organic-Inorganic Hybrid Perovskites: A New Platform for
      Optoelectronic Applications.
AB  - 2D perovskites are recently attracting a significant amount of attention, mainly
      due to their improved stability compared with their 3D counterpart, e.g., the
      archetypical MAPbI3 . Interestingly, the first studies on 2D perovskites can be
      dated back to the 1980s. The most popular 2D perovskites have a general formula
      of (RNH3 )2 MAn -1 Mn X3 n +1 , where n represents the number of metal halide
      octahedrons between the insulating organic cation layers. The optoelectronic
      properties of 2D perovskites, e.g., band gap, are highly dependent on the
      thickness of the inorganic layers (i.e., the value of n). Herein, 2D perovskites
      are arbitrarily divided into three classes, strict 2D (n = 1), quasi-2D (n = 2
      5), and quasi-3D (n > 5), and research progress is summarized following this
      classification. The majority of existing 2D perovskites only employ very simple
      organic cations (e.g., butyl ammonium or phenylethyl ammonium), which merely
      function as the supporting layer/insulating barrier to achieve the 2D structure.
      Thus, a particularly important research question is: can functional organic
      cations be designed for these 2D perovskites, where these functional organic
      cations would play an important role in dictating the optoelectronic properties
      of these organic-inorganic hybrid materials, leading to unique device performance
      or applications?

PMID- 30199109
TI  - High Tg and Thermo-Oxidatively Stable Thermosetting Polyimides Derived from a
      Carborane-Containing Diamine.
AB  - To provide high-temperature polyimide matrix resins, novel carborane-containing
      thermosetting polyimides are presented. First, the low-viscosity carborane
      containing imide oligomers are synthesized using newly designed 1-(3-amino-4
      tolyl)-2-(4-aminophenyl)-o-carborane and aromatic dianhydride as monomers, 4
      phenylethynyl phthalic anhydride as the end-capping reagent. Followed by thermal
      curing, the resulting polyimides show high Tg (>=500  degrees C) and above 92.1%
      char yield at 800  degrees C both in nitrogen and air atmosphere due to the
      incorporation of the bulky carborane cages. Aging studies, performed at 400 and
      500  degrees C for 5 h in air on a carborane-containing polyimide and a carborane
      free polyimide, show that the polyimide with carborane groups possesses excellent
      thermo-oxidative stability. Moreover, the novel polyimides exhibit constant and
      relatively low coefficient of thermal expansion values over a wide range of
      temperature, indicative of a remarkable dimensional stability. Thus, this study
      clearly demonstrates the viability of the incorporation of carborane cages to
      access polyimide thermosets with ultrahigh Tg and thermo-oxidative stability.

PMID- 30199110
TI  - Advances in mass spectrometry-based glycomics.
AB  - The diversification of the chemical properties and biological functions of
      proteins is attained through posttranslational modifications, such as
      glycosylation. Glycans, which are covalently attached to proteins, play a vital
      role in cell activities. The microheterogeneity and complexity of glycan
      structures associated with proteins make comprehensive glycomic analysis
      challenging. However, recent advancements in mass spectrometry (MS), separation
      techniques, and sample preparation methods have primarily facilitated structural
      elucidation and quantitation of glycans. This review focuses on describing recent
      advances in MS-based techniques used for glycomic analysis (2012-2018), including
      ionization, tandem MS, and separation techniques coupled with MS. Progress in
      glycomics workflow involving glycan release, purification, derivatization, and
      separation will also be highlighted here. Additionally, the recent development of
      quantitative glycomics through comparative and multiplex approaches will also be
      described.

PMID- 30199111
TI  - A Dual-Crosslinking Design for Resilient Lithium-Ion Conductors.
AB  - Solid-state electrolyte materials are attractive options for meeting the safety
      and performance needs of advanced lithium-based rechargeable battery technologies
      because of their improved mechanical and thermal stability compared to liquid
      electrolytes. However, there is typically a tradeoff between mechanical and
      electrochemical performance. Here an elastic Li-ion conductor with dual covalent
      and dynamic hydrogen bonding crosslinks is described to provide high mechanical
      resilience without sacrificing the room-temperature ionic conductivity. A solid
      state lithium-metal/LiFePO4 cell with this resilient electrolyte can operate at
      room temperature with a high cathode capacity of 152 mAh g-1 for 300 cycles and
      can maintain operation even after being subjected to intense mechanical impact
      testing. This new dual crosslinking design provides robust mechanical properties
      while maintaining ionic conductivity similar to state-of-the-art polymer-based
      electrolytes. This approach opens a route toward stable, high-performance
      operation of solid-state batteries even under extreme abuse.

PMID- 30199112
TI  - Optimal Destabilization of DNA Double Strands by Single-Nucleobase Caging.
AB  - Photolabile protecting groups are widely used to trigger oligonucleotide
      activity. The ON/OFF-amplitude is a critical parameter. An experimental setup has
      been developed to identify protecting group derivatives with superior caging
      properties. Bulky rests are attached to the cage moiety via Cu-catalyzed azide
      alkyne cycloaddition post-synthetically on DNA. Interestingly, the decrease in
      melting temperature upon introducing o-nitrobenzyl-caged (NPBY-) and
      diethylaminocoumarin-cages (DEACM-) in DNA duplexes reaches a limiting value. NMR
      spectroscopy was used to characterize individual base-pair stabilities and
      determine experimental structures of a selected number of photocaged DNA
      molecules. The experimental structures agree well with structures predicted by MD
      simulations. Combined, the structural data indicate that once a sterically
      demanding group is added to generate a tri-substituted carbon, the sterically
      less demanding cage moiety points towards the neighboring nucleoside and the
      bulkier substituents remain in the major groove.

PMID- 30199113
TI  - Absolute configurations of chiral molecules with multiple stereogenic centers
      without prior knowledge of the relative configurations: A case study of inuloxin
      C.

PMID- 30199115
TI  - The Dawn of Functional Organoarsenic Chemistry.
AB  - Organoarsenic chemistry was actively studied until the middle of 20th century.
      Although various properties of organoarsenic compounds have been computationally
      predicted, for example, frontier orbital levels, aromaticity, and inversion
      energies, serious concern to the danger of their synthetic processes has
      restricted experimental studies. Conventional synthetic routes require volatile
      and toxic arsenic precursors. Recently, nonvolatile intermediate transformation
      (NIT) methods have been developed to safely access functional organoarsenic
      compounds. Important intermediates in the NIT methods are cyclooligoarsines,
      which are prepared from nonvolatile inorganic precursors. In particular, the new
      approach has realized experimental studies on conjugated arsenic compounds:
      arsole derivatives. The elucidation of their intrinsic properties has triggered
      studies on functional organoarsenic chemistry. As a result, various kinds of
      arsenic-containing pi-conjugated molecules and polymers have been reported for
      the last few years. In this minireview, progress of this recently invigorated
      field is overviewed.

PMID- 30199114
TI  - Screening for morbidly adherent placenta in early pregnancy.
AB  - OBJECTIVE: To estimate the diagnostic accuracy of a two-stage strategy for early
      prediction of morbidly adherent placenta (MAP). In the first stage, at 11-13
      weeks' gestation, women with low-lying placenta and history of uterine surgery
      are classified as being at high risk for MAP and, in the second stage, at 12-16
      weeks, these high-risk pregnancies are assessed at a specialist MAP clinic.
      METHODS: This was a prospective study in women having an ultrasound scan at 11-13
      weeks' gestation as a part of routine pregnancy care. Women with low-lying
      placenta and a history of uterine surgery were followed up at a specialist MAP
      clinic at 12-16 weeks' gestation, 20-24 weeks and 28-34 weeks. At each visit to
      the MAP clinic, an ultrasound scan was carried out and the following features
      suggestive of MAP were recorded: non-visible Cesarean section scar; bladder wall
      interruption; thin retroplacental myometrium; presence of intraplacental lacunar
      spaces; presence of retroplacental arterial-trophoblastic blood flow; and
      irregular placental vascularization demonstrated by three-dimensional power
      Doppler. RESULTS: Screening at 11-13 weeks was carried out in 22 604 singleton
      pregnancies, 1298 (6%) of which were considered to be at high risk of MAP because
      they had previous uterine surgery and low-lying placenta. At the MAP clinic at 12
      16 weeks, the diagnosis of MAP was suspected in 14 cases and this was confirmed
      at delivery in 13. In the rest of the population, there were no cases of MAP.
      CONCLUSION: Accurate prediction of MAP can be achieved by ultrasound examination
      at 12-16 weeks' gestation. Copyright (c) 2018 ISUOG. Published by John Wiley &
      Sons Ltd.

PMID- 30199117
TI  - Glucocorticoids decrease the numbers and activation of mast cells by inducing the
      transactivation receptors of AGEs.
AB  - Glucocorticoids (GCs) are potent anti-allergic compounds that function, at least
      in part, by inhibiting signaling pathways in mast cells. We hypothesized that the
      GC-induced mastocytopenia and suppression of mast cell activation are mediated by
      the advanced glycation end products (AGEs)/receptors of AGEs (RAGEs) signaling
      axis. We evaluated the role of AGEs in GC-mediated mastocytopenia and impaired
      mast cell degranulation in male Wistar rats and Swiss-Webster mice subcutaneously
      injected with dexamethasone or prednisolone (0.1 mg/kg) once a day for 21
      consecutive days. The animals were treated with either the AGE inhibitor
      aminoguanidine (250 mg/kg), the RAGE antagonist FPS-ZM1 (1 mg/kg) or the galectin
      3 antagonist GSC-100 (1 mg/kg) daily for 18 days, starting 3 days following GC
      treatment. Aminoguanidine inhibited GC-induced mast cell apoptosis and restored
      mast cell numbers in the pleural cavity of GC-treated rats. Aminoguanidine also
      reversed the GC-induced reduction in histamine release triggered by allergens or
      compound 48/80 in vitro. GC treatment induced RAGE and galectin expression in
      mast cells, and blocking these agents by FPS-ZM1 or GSC-100 significantly
      reversed mast cell numbers in the peritoneal cavity and mesenteric tissue of GC
      treated mice. In addition, the combination of GC and AGE-induced mast cell
      apoptosis in vitro was inhibited by both FPS-ZM1 and GSC-100. We concluded that
      the GC-induced mastocytopenia and suppression of mast cell stimulation are
      associated with the gene transactivation of RAGE and galectin-3.

PMID- 30199118
TI  - Issue Highlights: September 2018.

PMID- 30199116
TI  - SPION-Decorated Nanofibers by RAFT-Mediated Free Radical Emulsion Polymerization
      Induced Self Assembly.
AB  - RAFT-mediated free-radical emulsion polymerization is successfully used to
      synthesize polystyrene nanofibers using triblock amphiphilic macro-RAFT
      copolymers as stabilizers. The polymerization is under RAFT control, producing
      various morphologies from spherical particles, nanofibers, nanoplatelets, and
      polymer vesicles. Optimum conditions are established for the synthesis of
      predominantly negatively charged polymer nanofibers. Superparamagnetic iron oxide
      nanoparticles (SPION)-decorated nanofibers are formed by simple mixing of the
      SPIONs with the fibers at an appropriate pH. The composite material has been
      found to be superparamagnetic and could be aligned under a magnetic field.

PMID- 30199120
TI  - Organocatalytic Regiodivergent C-C Bond Cleavage of Cyclopropenones: A Highly
      Efficient Cascade Approach to Enantiopure Heterocyclic Frameworks.
AB  - Here a highly efficient cascade approach is reported that combines a
      cycloaddition reaction with a regioselective strain-release process to afford
      diverse heterocyclic frameworks through bifunctional catalysis. The cooperation
      of hydrogen-bonding network activation and a regiodivergent strain-assisted
      effect is the key to promoting this complex chemical transformation, leading to
      the generation of two different ring systems in high yields with excellent
      stereoselectivities. The reaction proceeded by a mechanism involving a "spring
      loaded" intermediate with switchable C-C bond cleavages achieved by controllable
      ring-strain release. This reaction was also amenable to gram scale synthesis with
      only 0.1 mol % catalyst loading.

PMID- 30199122
TI  - Data Not Shown: Times have changed in scientific publishing and at the Veterinary
      Clinical Pathology journal.

PMID- 30199121
TI  - Analytical validation of platelet microparticle quantification in cats.
AB  - BACKGROUND: Cardiogenic embolism (CE) in cats is a devastating condition
      primarily associated with hypertrophic cardiomyopathy (HCM). Hypercoagulability
      may pose a risk for thrombus formation; however, no single test can predict CE
      development. Platelet microparticles (PMPs) released from platelet membranes are
      associated with thrombosis in humans. OBJECTIVES: The aims were to validate flow
      cytometric PMP quantification in cats analytically and, in a pilot study,
      evaluate the procoagulant annexin V (AnV) positive PMP concentration in healthy
      cats and cats with asymptomatic HCM. METHODS: With CD61 as a platelet marker,
      CD61+ AnV+ PMPs (0.3-1.0 MUm) were quantified in citrated whole blood (WB) and
      platelet-poor plasma (PPP) using flow cytometry. Analyses were performed in 6
      healthy cats and 5 cats with asymptomatic HCM. The coefficient of variation (CV)
      for duplicate (intra-assay) and parallel (inter-assay) analyses were calculated.
      RESULTS: PMP concentrations were quantified with acceptable intra-assay CV for WB
      (CD61+ /AnV- ; 2.4%, 0.2%-8.4% (median, range), CD61+ /AnV+ ; 3.8%, 0.1%-12.5%)
      and PPP (CD61+ /AnV- ; 5.0%, 0.7%-12.8%, CD61+ /AnV+ ; 7.4%, 0.5%-15.3%), and
      acceptable inter-assay CV for WB in 10/11 cats (CD61+ /AnV- ; 6.2%, 1.4%-13.3%,
      CD61+ /AnV+ ; 6.4%, 0.7%-17.2%), but unacceptable for PPP (CD61+ /AnV- ; 15.6%,
      5.8%-42.7%, CD61+ /AnV+ ; 27.8%, 8.4%-77.1%). For WB PMP concentrations, the
      pilot data demonstrated no differences between healthy cats and cats with
      asymptomatic HCM (4/5 with left ventricular outflow obstruction) for either the
      CD61+ /AnV- or the CD61+ /AnV+ PMPs. CONCLUSIONS: Only WB PMP concentrations
      could be quantified reliably in cats in a clinical setting. PMP concentrations
      did not differ between healthy and asymptomatic HCM cats in this pilot study.

PMID- 30199123
TI  - Research and diagnostic tool: the symmetric dimethylarginine case-for research
      use only.

PMID- 30199124
TI  - Reference intervals for coagulation variables in healthy adult domestic goats
      (Capra aegagrus hircus).
AB  - BACKGROUND: Coagulation has not been studied extensively in adult goats, and
      reference intervals (RIs) for coagulation variables have not yet been established
      and would be clinically useful. OBJECTIVES: The goal of this study was to
      establish coagulation variable RIs in adult goats for future coagulation
      interpretation. METHODS: Blood samples from 40 healthy adult goats were
      collected, and assays for PT, APTT, D-dimers, antithrombin III, and fibrinogen
      were performed. Coagulation variable RIs were established using the Reference
      Value Advisor v2.1. RESULTS: The RIs included: PT, 15.7-19.8 seconds; APTT, 16.2
      24.3 seconds; D-dimer, 0-0.68 MUg/mL; antithrombin III, 108.6%-156.5%;
      fibrinogen, 89.5-303.2 mg/dL. CONCLUSIONS: In this brief communication, we report
      the RIs for coagulation variables in healthy adult goats. Further research will
      be needed to identify coagulation changes that are associated with specific
      disease processes of goats.

PMID- 30199125
TI  - Ultrastabilization of Zeolite Y Transforms Bronsted-Bronsted Acid Pairs into
      Bronsted-Lewis Acid Pairs.
AB  - Two pairs of Bronsted acid sites have been identified in H,Na-Y zeolite, located
      in the supercage and in the sodalite cage, which upon ultrastabilization
      (dealumination) are transformed into pairs of Bronsted and Lewis acid sites. This
      mild postsynthetic modification step is an important process for converting this
      material into an active catalyst for large-scale commercial reactions. Pairing
      structures and their transformations have been investigated using 1 H double
      quantum NMR spectroscopy experiments for dehydrated zeolite, H,Na-Y, and its
      ultrastabilized form, H,Na-USY. This approach enables the detection of pairs of
      Bronsted and Lewis acid sites with unprecedented 1 H resolution and
      distinguishing them from isolated acid sites. The dealumination is also detected
      by static 27 Al solid-state NMR experiments.

PMID- 30199126
TI  - Outcomes for the First Year of Ontario's Birth Center Demonstration Project.
AB  - INTRODUCTION: In 2014, Ontario opened 2 stand-alone midwifery-led birth centers.
      Using mixed methods, we evaluated the first year of operations for quality and
      safety, client experience, and integration into the maternity care community.
      This article reports on our study of safety and quality of care. METHODS: This
      descriptive evaluation focused on women admitted to a birth center at the
      beginning of labor. For context, we matched this cohort (on a 1:4 basis) with
      similar low-risk midwifery clients giving birth in a hospital. Data sources
      included Ontario's Better Outcomes Registry and Network (BORN) Information
      System, the Canadian Institute for Health Information, Ontario census data, and
      birth center records. RESULTS: Of 495 women admitted to a birth center, 87.9%
      experienced a spontaneous vaginal birth, regardless of the eventual location of
      birth, and 7.7% had a cesarean birth. The transport rate to a hospital was 26.3%.
      When compared with midwifery clients with a planned hospital birth, rates of
      intervention (epidural analgesia, labor augmentation, assisted vaginal birth, and
      cesarean birth) were significantly lower in the planned birth center group, even
      when controlled for previous cesarean birth and body mass index. Markers of
      potential morbidity were identified in about 10% of birth center births; however,
      there were no short-term health impacts up to discharge from midwifery care at 6
      weeks postpartum. Care was low in intervention and safe (minimal negative
      outcomes and transport rates comparable to the literature). DISCUSSION: In the
      first year of operation, care was consistent with national guidelines, and
      morbidity and mortality rates and intervention rates were low for women with low
      risk pregnancies seeking a low-intervention approach for labor and birth. Further
      evaluation to confirm these findings is required as the number of births grows.

PMID- 30199127
TI  - The dosimetric effect of electron density overrides in 3DCRT Lung SBRT for a
      range of lung tumor dimensions.
AB  - The combined effects of lung tumor motion and limitations of treatment planning
      system dose calculations in lung regions increases uncertainty in dose delivered
      to the tumor and surrounding normal tissues in lung stereotactic body
      radiotherapy (SBRT). This study investigated the effect on plan quality and
      accuracy when overriding treatment volume electron density values. The QUASAR
      phantom with modified cork cylindrical inserts, each containing a simulated
      spherical tumor of 15-mm, 22-mm, or 30-mm diameter, was used to simulate lung
      tumor motion. Using Monaco 5.1 treatment planning software, two standard plans
      (50% central phase (50%) and average intensity projection (AIP)) were compared to
      eight electron density overridden plans that focused on different target volumes
      (internal target volume (ITV), planning target volume (PTV), and a hybrid plan
      (HPTV)). The target volumes were set to a variety of electron densities between
      lung and water equivalence. Minimal differences were seen in the 30-mm tumor in
      terms of target coverage, plan conformity, and improved dosimetric accuracy. For
      the smaller tumors, a PTV override showed improved target coverage as well as
      better plan conformity compared to the baseline plans. The ITV plans showed the
      highest gamma pass rate agreement between treatment planning system (TPS) and
      measured dose (P < 0.040). However, the low electron density PTV and HPTV plans
      also showed improved gamma pass rates (P < 0.035, P < 0.011). Low-density PTV
      overrides improved the plan quality and accuracy for tumor diameters less than 22
      mm only. Although an ITV override generated the most significant increase in
      accuracy, the low-density PTV plans had the additional benefit of plan quality
      improvement. Although this study and others agreed that density overrides improve
      the treatment of SBRT, the optimal density override and the conditions under
      which it should be applied were found to be department specific, due to
      variations in commissioning and calculation methods.

PMID- 30199129
TI  - Artificial intelligence: Implications for the health care risk manager?

PMID- 30199128
TI  - Moderating effect of comorbid anxiety disorders on treatment outcome in a
      randomized controlled psychotherapy trial in early-onset persistently depressed
      outpatients.
AB  - BACKGROUND: Persistent depressive disorder (PDD) is associated with high rates of
      comorbid psychiatric disorders, mostly anxiety disorders (ADs). Comorbid AD was
      found to be associated with poorer treatment outcome in PDD patients. The effect
      of comorbid AD on disorder-specific treatment for PDD (Cognitive Behavioral
      Analysis System of Psychotherapy [CBASP]) has not been studied yet. METHODS: We
      analyzed whether the presence of a comorbid AD was moderating the effectiveness
      of disorder-specific (CBASP) versus nonspecific psychotherapy (supportive therapy
      [SP]) on depressive symptoms (24-item Hamilton Rating Scale for Depression [HRSD
      24]) in a sample of unmedicated early-onset PDD outpatients (N = 268). Secondary
      outcomes were response and remission of depressive symptoms and the extent of
      interpersonal problems (Inventory of Interpersonal Problems [IIP-64]). RESULTS:
      The superiority of CBASP over SP was significantly stronger in PDD patients with
      comorbid AD compared to patients without AD (in HRSD-24 and IIP-64). There was no
      significant moderation for remission or response of depressive symptoms.
      DISCUSSION: Our hypothesis of a moderating effect of comorbid AD was confirmed.
      The main limitation might be the exclusion criteria of our sample limiting the
      generalizability. The major strength is the systematic analysis of the effect of
      AD in treating early-onset PDD with high quality of psychotherapy in both arms of
      this trial. CONCLUSION: Patients suffering from PDD comorbid with AD might
      experience greater benefit when they are treated with specific as opposed to
      unspecific therapy. Analyzing subgroups of patients with PDD seems worthwhile to
      improve treatment effectiveness even within disorder-specific treatment
      programms.

PMID- 30199130
TI  - Iridium-Catalyzed Electrooxidative C-H Activation by Chemoselective Redox
      Catalyst Cooperation.
AB  - Iridium-catalyzed electrochemical C-H activation was accomplished within a
      cooperative catalysis manifold, setting the stage for electrooxidative C-H
      alkenylations through weak O-coordination. The iridium-electrocatalyzed C-H
      activation featured high functional-group tolerance through assistance of a metal
      free redox mediator through indirect electrolysis. Detailed mechanistic insights
      provided strong support for an organometallic C-H cleavage and a synergistic
      iridium(III/I)/redox catalyst regime, enabling the use of sustainable electricity
      as the terminal oxidant with improved selectivity features.

PMID- 30199131
TI  - Modelling of ultraviolet light inactivation kinetics of methicillin-resistant
      Staphylococcus aureus, vancomycin-resistant Enterococcus, Clostridium difficile
      spores and murine norovirus on fomite surfaces.
AB  - AIMS: Quantitative data on the doses needed to inactivate micro-organisms on
      fomites are not available for ultraviolet applications. The goal of this study
      was to determine the doses of UV light needed to reduce bacteria and murine
      norovirus (MNV) on hard surface fomites through experimentation and to identify
      appropriate models for predicting targeted levels of reduction. METHODS AND
      RESULTS: Stainless steel and Formica laminate coupons were selected as they are
      common surfaces found in healthcare settings. Test organisms included methicillin
      resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE),
      Clostridium difficile and MNV. The fomites were inoculated with 105 -107 bacteria
      or virus and exposed to a range of UV doses. The order of resistance to UV
      irradiation was virus, bacterial spore and vegetative cell. The best fitting
      inactivation curves suggested nonlinear responses to increasing doses after a 3-4
      log reduction in the test organisms. The average UV doses required for a 3 log
      reduction in the C. difficile, MRSA and VRE were 16 000, 6164 and 11 228 (mJ-s cm
      2 ) for stainless steel, respectively, and 16 000, 11 727 and 12 441 (mJ-s cm-2 )
      for Formica laminate, respectively. CONCLUSIONS: Higher UV light doses are
      required to inactivate bacteria and viruses on hard surfaces than in suspension.
      Greater doses are needed to inactivate bacterial spores and MNV compared to
      vegetative bacteria. SIGNIFICANCE AND IMPACT OF THE STUDY: Quantitative data and
      models on UV light doses needed to inactivate bacteria and MNV on hard surfaces
      are now available. The generalizable results of this study can be used to
      estimate required UV dosages to achieve targeted levels of inactivation based on
      estimated levels of contamination or to support quantitative microbial risk
      assessments.

PMID- 30199132
TI  - Sulfur Polymers Meet Poly(ionic liquid)s: Bringing New Properties to Both Polymer
      Families.
AB  - Sulfur-containing polymers and poly(ionic liquid)s are emerging macromolecules
      with unique properties and applications. This article shows the first integration
      of these two polymer families, leading to materials with a unique combination of
      properties. The synthetic strategy toward sulfur-containing poly(ionic liquid)s
      involves first the copolymerization of elemental sulfur with 4-vinylbenzyl
      chloride and subsequent quaternization of the alkyl chloride group using N-methyl
      imidazole. The synthetic pathway is completed by the anion exchange reaction of
      the poly(sulfur-co-4-vinylbenzyl imidazolium chloride) by a sulphonamide anion.
      The obtained polymers are fully characterized by NMR, FTIR, SEC, DSC, and TGA.
      The sulfur poly(ionic liquid)s combine some properties related to its poly(ionic
      liquid) nature, such as anion-dependent solubility (water vs organic solvents)
      and high ionic conductivity as well as properties related to its sulfur content,
      such as redox activity.

PMID- 30199133
TI  - Separation Innovations: Honoring Frantisek Svec on his 75th Birthday.

PMID- 30199136
TI  - Current Resources for Evidence-Based Practice, September/October 2018.

PMID- 30199134
TI  - Thiols and Solvents Coordinated Cation Exchange Kinetics for Novel Semiconductor
      Nanocrystal Engineering.
AB  - Including the composition and crystallinity, novel nanocrystal engineering (the
      atomic impurities doping and hetero-interface to metal) has been achieved by
      various thiols and solvents coordinated cation exchange kinetics. The detailed
      mechanism about this novel reaction thermodynamics and kinetics was explored by
      NMR, time dependent photoluminescence (PL) characterizations and theoretical
      simulations. The fine structure of colloidal semiconductor nanocrystals (CSNCs)
      was investigated by X-ray absorption near edge structure (XANES) and extended X
      ray absorption fine structure (EXAFS). Enabled by such, high-quality p-type Ag
      doped ZnS quantum dots (QDs) and Au@ZnS hetero-nanocrystals with cubic phase ZnS
      shell were synthesized successfully. The unprecedented dominant Ag+ dopant
      induced fluorescence and p-type conductivity in zinc-blende ZnS host have been
      reported.

PMID- 30199135
TI  - Explaining variability in therapist adherence and patient depressive symptom
      improvement: The role of therapist interpersonal skills and patient engagement.
AB  - Understanding why therapists deviate from a treatment manual is crucial to
      interpret the mixed findings on the adherence-outcome association. The current
      study aims to examine whether therapists' interpersonal behaviours and patients'
      active engagement predict treatment outcome and therapist adherence in cognitive
      behaviour therapy (CBT) and mindfulness-based cognitive therapy (MBCT) for
      depressive symptoms. In addition, the study explores rater's explanations for
      therapist nonadherence at sessions in which therapist adherence was low. Study
      participants were 61 patients with diabetes and depressive symptoms who were
      randomized to either CBT or MBCT. Depressive symptoms were assessed by the Beck
      Depression Inventory-II. Therapist adherence, therapist interpersonal skills
      (i.e., empathy, warmth, and involvement), patients' active engagement, and
      reasons for nonadherence were assessed by two independent raters (based on
      digital video recordings). Therapist adherence, therapists' interpersonal skills,
      and patients' active engagement did not predict posttreatment depressive symptom
      reduction. Patients' active engagement was positively associated with therapist
      adherence in CBT and in MBCT. This indicates that adherence may be hampered when
      patients are not actively engaged in treatment. Observed reasons for nonadherence
      mostly covered responses to patient's in-session behaviour. The variety of
      reasons for therapist nonadherence might explain why therapist adherence was not
      associated with outcomes of CBT and MBCT.

PMID- 30199137
TI  - Lipoplex-Mediated Single-Cell Transfection via Droplet Microfluidics.
AB  - While lipoplex (cationic lipid-nucleic acid complex)-mediated intracellular
      delivery is widely adopted in mammalian cell transfection, its transfection
      efficiency for suspension cells, e.g., lymphatic and hematopoietic cells, is
      reported at only ~5% or even lower. Here, efficient and consistent lipoplex
      mediated transfection is demonstrated for hard-to-transfect suspension cells via
      a single-cell, droplet-microfluidics approach. In these microdroplets,
      monodisperse lipoplexes for effective gene delivery are generated via chaotic
      mixing induced by the serpentine microchannel and co-confined with single cells.
      Moreover, the cell membrane permeability increases due to the shear stress
      exerted on the single cells when they pass through the droplet pinch-off
      junction. The transfection efficiency, examined by the delivery of the pcDNA3
      EGFP plasmid, improves from ~5% to ~50% for all three tested suspension cell
      lines, i.e., K562, THP-1, Jurkat, and with significantly reduced cell-to-cell
      variation, compared to the bulk method. Efficient targeted knockout of the
      TP53BP1 gene for K562 cells via the CRISPR (clustered regularly interspaced short
      palindromic repeats)-CAS9 (CRISPR-associated nuclease 9) mechanism is also
      achieved using this platform. Lipoplex-mediated single-cell transfection via
      droplet microfluidics is expected to have broad applications in gene therapy and
      regenerative medicine by providing high transfection efficiency and low cell-to
      cell variation for hard-to-transfect suspension cells.

PMID- 30199138
TI  - Near-Infrared Semiconducting Polymer Brush and pH/GSH-Responsive Polyoxometalate
      Cluster Hybrid Platform for Enhanced Tumor-Specific Phototheranostics.
AB  - Tumor-specific phototheranostics is conducive to realizing precise cancer
      therapy. Herein, a novel tumor microenvironment (TME)-responsive phototheranostic
      paradigm based on the combination of semiconducting polymer brushes and
      polyoxometalate clusters (SPB@POM) is rationally designed. The acidic TME could
      drive the self-assembly of SPB@POM into bigger aggregates for enhanced tumor
      retention and accumulation, while the reducing TME could significantly enhance
      the NIR absorption of SPB@POM for significant improvement of photoacoustic
      imaging contrast and photothermal therapy efficacy. Therefore, the smart
      pH/glutathione (GSH)-responsive SPB@POM allows for remarkable phototheranostic
      enhancement under the unique TME, which has potential for precise tumor-specific
      phototheranostics with minimal side effects.

PMID- 30199139
TI  - MXene Aerogel Scaffolds for High-Rate Lithium Metal Anodes.
AB  - Li metal is considered to be an ultimate anode for metal batteries owing to its
      extremely high theoretical capacity and lowest potential. However, numerous
      issues such as short lifespan and infinite volume expansion caused by the
      dendrite growth during Li plating/stripping hinder its practical usage. These
      challenges become more grievous under high current densities. Herein, 3D porous
      MXene aerogels are proposed as scaffolds for high-rate Li metal anodes using Ti3
      C2 as an example. With high metallic electron conductivity, fast Li ion transport
      capability, and abundant Li nucleation sites, such scaffolds could deliver high
      cycling stability and low overpotential at current density up to 10 mA cm-2 .
      High rate performance is also demonstrated in full cells with LiFePO4 as
      cathodes. This work provides a new type of scaffolds for Li metal anodes and
      paves the way for the application of non-graphene 2D materials toward high energy
      density Li metal batteries.

PMID- 30199140
TI  - Proctectomy and ileal pouch anal anastomosis for ulcerative colitis with diffuse
      enteritis after colectomy - a video vignette.

PMID- 30199141
TI  - Physiochemical properties of Trichoderma longibrachiatum DSMZ 16517-synthesized
      silver nanoparticles for the mitigation of halotolerant sulphate-reducing
      bacteria.
AB  - AIMS: In order to efficiently control the corrosive sulphate-reducing bacteria
      (SRB), the main precursor of the microbial influenced corrosion (MIC) in oil
      industry, the ability of Trichoderma longibrachiatumDSMZ 16517 to synthesize
      silver nanoparticles (AgNPs) was investigated and their biocidal activity against
      halotolerant SRB was tested. METHODS AND RESULTS: The mycelial cell-free filtrate
      (MCFF) bioreduced the silver ions (Ag+ ) to their metallic nanoparticle state
      (Ag0 ), which was presumptively indicated by the appearance of a dark brown
      suspension and confirmed by the characteristic absorbance of AgNPs at y422nm .
      One-factor-at-a-time technique was used to optimize the effect of temperature,
      time, pH, fungal biomass and silver nitrate concentrations, stirring rates and
      dark effect. The dynamic light scattering (DLS) analysis revealed average AgNPs
      size and zeta potential values of 17.75 nm and -26.8 mV, respectively, indicating
      the stability of the prepared AgNPs. The X-ray diffraction (XRD) pattern assured
      the crystallinity of the mycosynthesized AgNPs, with an average size of 61 nm.
      The field emission scanning electron microscope (FESEM) and high-resolution
      transmission electron microscope (HRTEM) showed nonagglomerated spherical,
      triangular and cuboid AgNPs ranging from 5 to 11 +/- 0.5 nm. The Fourier
      transform infrared spectroscopy (FT-IR) analysis of the mycosynthesized AgNPs
      affirmed the role of MCFF as a reducing and capping agent. A preliminary
      suggested mechanism for mycosynthesis of AgNPs was elucidated. The
      mycosynthesized AgNPs expressed high biocidal activity against a halotolerant
      planktonic mixed culture of SRB. The HRTEM analysis showed a clear evidence of an
      alteration in cell morphology, a disruption of SRB cell membranes, a lysis in
      cell wall and a cytoplasmic extraction after treatment with AgNPs. This confirmed
      the bactericidal effect of the mycosynthesized AgNPs. CONCLUSION: The biocidal
      activity of the mycosynthesized AgNPs against halotolerant planktonic SRB makes
      it an attractive option to control MIC in the petroleum industry. SIGNIFICANCE
      AND IMPACT OF THE STUDY: This research provides a helpful insight into the
      development of a new mycosynthesized biocidal agent against the corrosive
      sulphate-reducing bacteria.

PMID- 30199142
TI  - C?H Activation as a Shortcut to Conjugated Polymer Synthesis.
AB  - Direct (hetero)arylation polymerization exploits the palladium-catalyzed
      activation of aromatic C?H bonds for the atom-economical synthesis of conjugated
      polymers for a wide range of applications. This account outlines how direct
      arylation methodologies overcome many of the limitations of contemporary
      polymerization techniques at both the research and production scale, and explains
      how monomer design and reaction conditions must be tailored to ensure high
      polymer molecular weight, yield, and structural integrity. Current research aims
      to improve further this reaction's profile as a sustainable methodology while at
      the same time making it competitive with the Migita-Stille and Miyaura-Suzuki
      polymerizations both in scope of accessible structures and synthetic efficiency.
      This feature article charts the recent developments and future directions of C?H
      activation research as it moves toward becoming at once an industrially feasible,
      environmentally friendly, and synthetically powerful polymerization technique.

PMID- 30199143
TI  - The Mexican Experience Adapting CenteringPregnancy: Lessons Learned in a Publicly
      Funded Health Care System Serving Vulnerable Women.
AB  - Group antenatal care is an innovative model of health care in which all
      components of antenatal care-clinical, educational, and supportive-happen in a
      group context with health care professionals as facilitators. CenteringPregnancy
      is the most studied model of group antenatal care, now widely implemented in the
      United States. This model has been shown to be effective in improving health and
      behavioral outcomes in the United States, but there is less known about the
      experience adapting group antenatal care in settings outside the US health care
      system. This article describes the adaptation of the CenteringPregnancy model to
      a Mexican context. We describe the Mexican health care context and our adaptation
      process and highlight key factors to consider when adapting the content and
      modality of the CenteringPregnancy model for diverse populations and health
      systems. Our findings are relevant to others seeking to implement group antenatal
      care in settings outside the US health care system.

PMID- 30199145
TI  - A Fresh New Look, and a Fresh New Journal.
AB  - The founding of Arthritis & Rheumatism by the American Rheumatism Association in
      1958 occurred at the advent of knowledge of immunologic abnormalities in patients
      with rheumatoid arthritis, SLE, and related disorders. Over its ensuing 60 year
      history, "A&R" (renamed to Arthritis & Rheumatology in 2014) developed into a
      preeminent publication for disseminating research findings and advancing the
      field scientifically. Landmark papers included the role of autoantibodies and
      lymphocytes in rheumatic diseases and, in recent years, the clinical translation
      of cell and cytokine-based paradigms of disease. This article is protected by
      copyright. All rights reserved.

PMID- 30199144
TI  - The association between anxiety, traumatic stress, and obsessive-compulsive
      disorders and chronic inflammation: A systematic review and meta-analysis.
AB  - BACKGROUND: Anxiety is characterized by prolonged preparation for real or
      perceived threat. This may manifest both as psychological and physiological
      activation, ultimately leading to greater risk for poor health. Chronic
      inflammation may play an integral role in this relationship, given the
      influential role that it has in chronic illness. The aim of this meta-analysis is
      to examine levels of chronic inflammation, measured by inflammatory cytokines and
      C-reactive protein, in people with anxiety disorders, PTSD (posttraumatic stress
      disorder), or obsessive-compulsive disorder compared to healthy controls. Several
      moderating variables, including specific diagnosis and depression comorbidity,
      were also assessed. METHODS: Seventy six full-text articles were screened for
      eligibility with 41 studies ultimately included in analysis. RESULTS: Results
      demonstrated a significant overall difference between healthy controls (HCs) and
      people with anxiety disorders in pro-inflammatory cytokines (P = 0.013, Hedge's g
      = -0.39), which appears to be largely driven by interleukin-1beta (IL-1beta; P =
      0.009, Hedge's g = -0.50), IL-6 (P < 0.001, Hedge's g = -0.93), and tumor
      necrosis factor-alpha (P = 0.030, Hedge's g = -0.56). Moderation analyses
      revealed a moderating effect of diagnosis (P = 0.050), as only individuals with
      PTSD demonstrated differences in inflammation between HCs (P = 0.004, Hedge's g =
      -0.68). CONCLUSIONS: These data demonstrate the association between inflammatory
      dysregulation and diagnoses associated with chronic, impactful, and severe
      anxiety and provides insight into the way that anxiety, and in particular PTSD,
      is related to certain inflammatory markers. In doing so, these findings may
      provide an initial step in disentangling the relationship between anxiety and
      basic health processes.

PMID- 30199146
TI  - Characterization of Membrane Proteins Using Cryo-Electron Microscopy.
AB  - The steep increase of atomic scale structures determined by 3D cryo-electron
      microscopy (EM) deposited in the EMDataBank documents progress of a methodology
      that was frustratingly slow ten years ago. While sample vitrification on grids
      has been successfully used in all EM laboratories for decades, beam damage
      remains a road block. Developments in instrumentation and software to exploit the
      information carried by elastically scattered electrons made the task to achieve
      atomic scale resolution easier. This together with the development of fast single
      electron detecting cameras has resulted in unprecedented possibilities for
      structure determination by 3D cryo-EM. With such technologies in place, the
      purification of membrane protein complexes in a functional state is key to
      collecting atomic scale structural information and insight into the chemistry of
      physiological processes. Therefore, we focus here on the preparation of membrane
      proteins for structural analyses by 3D cryo-EM and the data acquisition of such
      vitrified samples. (c) 2018 by John Wiley & Sons, Inc.

PMID- 30199147
TI  - Symmetrical Diamidates as a Class of Phosphate Prodrugs to Deliver the 5'
      Monophosphate Forms of Anticancer Nucleoside Analogues.
AB  - The application of phosphorodiamidate technology to pyrimidine and purine
      nucleosides with anticancer activity to potentially overcome the resistance
      mechanisms associated with parent nucleosides is reported. Sixteen symmetrical
      phosphorodiamidates were prepared from the natural amino acids l-alanine and
      glycine. All the compounds were evaluated for their cytotoxic activity against a
      wide panel of solid and leukaemic tumour cell lines. In addition, a
      carboxypeptidase Y assay was performed on a representative phosphorodiamidate in
      order to reveal the putative bioactivation pathway for the reported
      phosphorodiamidate-type prodrugs.

PMID- 30199148
TI  - Molecular genetic alterations in thyroid transcription factor 1-negative lung
      adenocarcinoma in cytology specimens: A subset with aggressive behavior and a
      poor prognosis.
AB  - BACKGROUND: Patients with thyroid transcription factor 1 (TTF1)-negative
      pulmonary adenocarcinoma (ADC) have been reported to have a worse prognosis and
      to lack epidermal growth factor receptor (EGFR) mutations. This study describes a
      series of cytology specimens from patients with clinically confirmed pulmonary
      carcinoma negative for TTF1. METHODS: A search for TTF1-negative ADC from 2010 to
      2017 was performed. Each patient's clinical history, pathology specimens, and
      molecular results were noted. Two hundred ten patients with TTF1-positive
      pulmonary ADC formed the control group. RESULTS: Fifty specimens were identified
      from 50 patients (26 females and 24 males). The median age was 58.5 years. The
      smoking history was as follows: 38 smokers/former smokers (76%), 10 nonsmokers
      (20%), and 2 patients with an unknown status (4%). Thirty-nine patients (78%) had
      no previous history of malignancy. The clinical stages were as follows: stage I
      or II (n = 2 [4%]), stage III (n = 9 [18%]), stage IV (n = 37 [74%]), and unknown
      (n = 2 [4%]). Patients' mean survival was 10.3 months. Molecular results were
      available in 43 cases. Twenty-seven cases (63%) had no mutation identified; when
      they were compared with the control group, TTF1-negative patients had overall
      shorter survival (P = .0047), even though no statistically significant difference
      was seen on the clinical stage. Known mutations were less frequent (P = .0095) in
      TTF-negative tumors (KRAS mutations, n = 11 [25%]; anaplastic lymphoma kinase
      [ALK], n = 3 [7%]; and EGFR, n = 2 [5%]). This was particularly true for EGFR
      mutations (P = .047). However, ALK rearrangements were present at an increased
      frequency in the TTF1-negative group (P = .018). CONCLUSIONS: Patients with TTF1
      negative lung ADC have worse overall survival, a lower frequency of known
      mutations, and a higher frequency of ALK alterations.

PMID- 30199149
TI  - A 3D Haloplumbate Framework Constructed From Unprecedented Lindqvist-like Highly
      Coordinated [Pb6 Br25 ]13- Nanoclusters with Temperature-Dependent Emission.
AB  - Searching novel haloplumbate building units to construct three-dimensional (3D)
      frameworks is very important and highly desirable because such materials would
      possess new physical properties and potential applications. Here, by employing
      tetrakis(N-imidazolemethylene)methane(TIMM) as a structure-directing agent, the
      first 3D haloplumbate framework constructed from unprecedented Lindqvist-like
      highly coordinated [Pb6 Br25 ]13- nanoclusters has been successfully prepared
      under hydrothermal condition, where all Pb2+ centres in [Pb6 Br25 ]13-
      nanoclusters adopt seven-/eight-coordinated configurations. The as-obtained
      material is a wide-gap semiconductor (~3.1 eV) and can be stable up to 320 
      degrees C. More importantly, this material has been demonstrated to show
      temperature-dependent emission. Our results could provide a new strategy to
      explore novel metal-halide open-framework materials.

PMID- 30199150
TI  - A Guided Protocol for Array Based T2C: A High-Quality Selective High-Resolution
      High-Throughput Chromosome Interaction Capture.
AB  - After now more than 170 years of research the dynamic three-dimensional chromatin
      architecture of genomes and the co-evolved interaction networks of regulatory
      elements which create genome function - i.e. the storage, expression, and finally
      replication of genetic information - involves ever more investigative efforts in
      respect to not only the pure understanding of living organisms, but also
      diagnosis, treatment, and even future genome engineering. To study genomic
      interactions, we developed a novel and superior high-quality selective high
      resolution, high-throughput chromosome interaction capture method - T2C (targeted
      chromatin capture) - which allows to arbitrarily balance resolution, frequency
      range of interactions, and the investigated general genetic region or single
      interactions in a highly cost-effective manner in respect to the obtainable
      result and compared to other techniques. Beyond, T2C has such a high signal-to
      noise ratio at high resolution that the "genomic" statistical mechanics level can
      be reached. With the guided T2C protocol described here, we were already able to
      finally determine the chromatin quasi-fiber conformation and its folding into
      stable multi-loop aggregates/rosettes connected by a linker. Actually, this
      guided T2C protocol provides the means for architectural genome sequencing from
      the level of the single base pair to the entire cell nucleus and thus to analyze
      genetic interactions in respect to genome function in a systems biological manner
      in general as well as in settings ranging from basic research, via diagnostics
      and treatment, to genome engineering. (c) 2018 by John Wiley & Sons, Inc.

PMID- 30199151
TI  - Axitinib: A Photoswitchable Approved Tyrosine Kinase Inhibitor.
AB  - The goal of photopharmacology is to develop photoswitchable enzyme modulators as
      tunable (pro-)drugs that can be spatially and temporally controlled by light. In
      this context, the tyrosine kinase inhibitor axitinib, which contains a
      photosensitive stilbene-like moiety that allows for E/Z isomerization, is of
      interest. Axitinib is an approved drug that targets the vascular endothelial
      growth factor receptor 2 (VEGFR2) and is licensed for second-line therapy of
      renal cell carcinoma. The photoinduced E/Z isomerization of axitinib has been
      investigated to explore if its inhibitory effect can be turned "on" and "off", as
      triggered by light. Under controlled light conditions, (Z)-axitinib is 43 times
      less active than that of the E isomer in an VEGFR2 assay. Furthermore, it was
      proven that kinase activity in human umbilical vein cells (HUVECs) was decreased
      by (E)-axitinib, but only weakly affected by (Z)-axitinib. By irradiating (Z)
      axitinib in vitro with UV light (lambda=385 nm), it is possible to switch it
      almost quantitatively into the E isomer and to completely restore the biological
      activity of (E)-axitinib. However, switching the biological activity off from (E)
      to (Z)-axitinib was not possible in aqueous solution due to a competing
      irreversible [2+2]-photocycloaddition, which yielded a biologically inactive
      axitinib dimer.

PMID- 30199152
TI  - [Fingerprint Properties of Semi Synthetic Penicillin Pharmaceutical Wastewater].
AB  - High-concentration antibiotics are detected in surface water from time to time.
      There has been an increasing demand for strengthening the supervision of the
      antibiotic pharmaceutical wastewater. Three-dimensional fluorescence technique is
      known as a rapid, simple and high-sensitivity method. The three-dimensional
      fluorescence spectrum can display organic components and it was named as aqueous
      fingerprint. In this paper, three-dimensional fluorescence characteristics of a
      typical semi synthetic penicillin pharmaceutical wastewater were studied. There
      were totally four fluorescence peaks in the aqueous fingerprint of this
      wastewater, locating in excitation wavelength/emission wavelength of 360/445,
      255/445, 275/305 and 230/300 nm respectively. Fluorescence peak's intensity
      within certain range related linearly to the relative concentration. The possible
      fluorescent pollutants related to Peak C and Peak D might be the mixture of D-(-)
      A-4-Hydroxyphenylglycine Dane Salt Methyl Potassium (pharmaceutical
      intermediates), Amoxicillin (pharmaceutical product) and D(-)-4
      Hydroxyphenylglycine (pharmaceutical hydrolysate). PH played an important role in
      the fluorescence characteristics of this wastewater. This indicated that the
      fluorescent organic pollutants in this wastewater might contain acid or base
      groups. The aqueous fingerprint technique could be used to monitor the discharge
      of semi synthetic penicillin pharmaceutical wastewater as a novel tool.

PMID- 30199153
TI  - [Compositional Characteristics of Sediment Dissolved Organic Nitrogen in Typical
      Lakes and Its Relationship on Water Trophic Status].
AB  - UV-Vis absorbance, fluorescence, and Gas Chromatography Mass Spectrometry (GC-MS)
      were applied to the comparative study on sediment dissolved organic nitrogen
      (DON) in five typical lakes (Erhai lake, Dianchilake, Poyang lake, Wuhan Dong
      lake, and Taihu lake) in different lake regions with different nutrition status,
      revealing the relationship between structural and compositional characteristics
      of sediment DON and trophic level of lakes. The obtained results showed that:
      1Structure of lake sediment DON in Yungui Plateau region is more stable, compared
      with those in Eastern Plain region, indicating its lower bioavailability. 2In
      Yungui Plateau region, the source and compositional characteristics of sediment
      DON weremore complex in Dianchi lake (a seriously polluted lake), and its
      sediment DON bioavailabilitywas relatively higher. While, with respect to the
      less polluted Erhai lake, the source of sediment DON is more simple with a higher
      stability in DON structure and composition, which is beneficial for maintaining
      its good water quality. 3In Eastern Plain region, nutrition status of Taihu lake
      was similer to Donghu lake. The structure and composition of sediment DON was
      complex. But the lower aromaticityand fewer Aromatic ring substituents abundance
      made their relatively weak nutrient retention ability, posing risk to water
      quality. With regard to Poyang Lake, the structure and composition of sediment
      DON was relatively simple, but nutrient retention ability was relatively strong,
      which played a positive role in maintaining good water quality. 4P(III+V,
      n)/P(I+II, n) values(the content ratio of humic-like substanceto protein-like
      substances)were in sequence of Dianchi Lake (33.14)>Erhai Lake(21.49)>Taihu
      Lake(9.06)>Donghu Lake(7.04)>Poyang Lake(4.83), while E(4)/E(6) values (the ratio
      of UV-Vis absorbance at 465 and 665 nm) were in sequence of Dianchi Lake
      (27.00)>Donghu Lake(6.65)>Poyang Lake(5.47)>Taihu(3.50)>Erhai Lake(2.31). In
      addition, P(III+V, n)/P(I+II, n) and E(4)/E(6) valueswere positively correlated
      with thecontents of the different nitrogen (N) forms in the sediments. The above
      information suggested that P(III+V, n)/P(I+II, n) and E(4)/E(6) values exhibited
      good discrimination degree among different trophic status lakes, and they were
      considered to indirectly indicate the nutrition levels of lakes to a certain
      extent.

PMID- 30199154
TI  - MECHANICAL IMPACT ON THE CELL COVERING FINE STRUCTURE OF DINOFLAGELLATES
      PROROCENTRUM MINIMUM.
AB  - Complex cell coverings (amphiesma) of potentially toxic dinoflagellates
      Prorocentrum minimum includeplasma membrane and flattened amphiesmal vesicles
      with thecal cellulose plates. Two largest thecal plates surroundthe major portion
      of dinoflagellate cell as shell valves. We have revealed that P. minimum cells
      appear tobe extremely sensitive to the physical stress: even low speed
      centrifugation (1200 and 2000 g) leads to a droppingof old coverings shedding
      (ecdysis) and the formation of viable spheroplasts. Spheroplasts are
      surroundedonly by the plasma membrane beneath which the new amphiesma is formed.
      These spheroplasts can be a convenientmodel system for investigation of numerous
      aspects of cell and molecular biology of the dinoflagellates.

PMID- 30199155
TI  - ULTRASTRUCTURAL DIFFERENCES OF PRESPORES DEVELOPMENTAL STAGES AND MEIOSPORES OF
      SPECIES OF CLOSELY RELATED MICROSPORIDIA OF GENERA AMBLYOSPORA AND
      TRICHOCTOSPOREA (AMBLYOSPORIDAE: MICROSPORIDIA) FROM BLOOD-SUKING MOSQUITOES OF
      THE GENUS AEDES (DIPTERA: CULICIDAE).
AB  - Ultrastructure of prespore developmental stages, with emphasis on meiospores, has
      been examined in closelyrelated genera of Microsporidia, Amblyospora and
      Trichoctosporea, isolated from larvae adipose tissueof mosquitoes Aedes in order
      to compare morphology of these parasites. Ultrastructural differences
      betweenAmblyospora and Trichoctosporea have been found to concern the secret
      filling episporal space of sporophorousvesicle, wall of mature spores, the
      polaroplast and membranes of thin coils of polar tubes. The episporal
      secretcontributes to formation of meiospore wall and its structure is one of key
      systematic features to be consideredin the identification of microsporidia.

PMID- 30199156
TI  - TRP NHANNELS IN THE ENDOSOMAL PATHWAY.
AB  - The TRP (transient receptor potential) superfamily consists of a wide range of
      cation channels with differentphysiological functions and different cellular
      distribution. The TRP channels are implicated in pain perception,hearing and
      temperature sensation, photoreception, mechanotransduction, Ca2+-(re)absorption,
      cell proliferationand differentiation. Initially it was believed that TRP
      channels exist exclusively in the plasma membraneof the cells. Now this view is
      changing, since many members of this superfamily were found in theintracellular
      organelles where they successfully fulfill their conductive function. This review
      presents the currentdata concerning the members of the superfamily of TRP, which
      are integrated into the intracellular compartments.The role of TRP channels in
      the complicated and multicomponent machinery of endosomal pathways isanalyzed.

PMID- 30199157
TI  - CELL CULTURES PURITY CONTROL BY METHODS OF CLINICAL DIAGNOSTICS.
AB  - Cell cultures of higher organisms, especially cultures of human cells, are
      increasingly used in medical,pharmaceutical and scientific research. The main
      problem of cell cultures - non-lethal hidden contaminationby mycoplasmas, viruses
      and outsider cell lines. As an available and reliable method for monitoring the
      purityof the cell cultures, we offer to use PCR kits designed and officially used
      in clinical diagnostics. We have tested50 human cell lines using commercial
      diagnostic systems for detection of papilloma viruses, herpes
      viruses,adenoviruses, Mycoplasma hominis and total bacterial mass. Contamination
      in tested cell lines was not found.In the case of cell lines that contain
      integrated parts of viral genomes, the presence of the respective DNA
      sequenceswas confirmed. The proposed diagnostic systems can be effectively used
      to control the purity of cell lines,for qualitative detection of possible
      contamination, as well as for quantitative evaluations with calculationof viral
      load like it is practiced in clinical diagnostics.

PMID- 30199158
TI  - GLIOMA CELL PROLIFERATION MEDIATED BY COENZYME Q10 AT SERUM DEPRIVATION IN VITRO.
AB  - Mechanisms of coenzyme Q10 effect on serum-deprived glioma cell proliferation
      have been studied. Ourresults have shown that the addition of coenzyme Q10 into
      serum-free culture medium leads to increase in cellviability, stimulation of cell
      growth, as well as restoration of mitochondrial potential and increase of
      quantity ofenergized mitochondria. It has been found out that coenzyme Q10
      induced glioma cell proliferation under serumdeficiency is a result of
      intracellular reduced glutathione concentration decrease with subsequent
      activation ofproteinkinase C, ERK1/2 and phosphoinositol-3-kinase.

PMID- 30199159
TI  - THE ROLE OF LMNA MUTATIONS IN MYOGENIC DIFFERENTIATION OF PRIMARY SATELLITE CELLS
      AND C2C12 CELLS.
AB  - Nuclear lamins form nuclear lamina localized under the inner nuclear membrane. It
      was previously consideredthat the nuclear lamina predominantly plays a structural
      role, however, its involvement have been recentlydescribed in the regulatory
      processes such as chromatin organization and gene transcription. It is known
      thatmutations in the LMNA gene lead to the development of a large number of
      diseases, laminopathies, which mainlyaffect mesenchymal tissue. Nowadays, the
      mechanisms by which the lamina can regulate cell differentiationremain
      incompletely understood. In the present work, we have studied the effect of LMNA
      gene mutations onthe process of muscle differentiation of primary satellite cells
      and N2N12 cell line. The genome of satellite cellsand N2N12 cell line was
      modified by the introduction of lentiviral constructs encoding LMNA G232E
      associatedwith the development of muscular dystrophy Emery-Dreyfus and LMNA R571S
      associated with the developmentof dilated cardiomyopathy. The morphology of the
      cells was estimated using immunofluorescence, theexpression level of myogenic
      genes were analyzed by qPCR. We have shown that the analyzed mutations reducethe
      ability of cells to differentiate, to fuse and to form myotubes. We have
      suggested that it is due to enhancedexpression of markers at the early stages and
      to reduced expression markers at the late stages of myogenesis.Therefore,
      mutations in nuclear lamins can influence the process of muscle differentiation.

PMID- 30199160
TI  - THE EFFECT OF LYSOPHOSPHATIDIC ACID ON THE COMPOSITION OF MYOSIN-9 AND
      TROPOMYOSIN CONTAINING CYTOPLASMIC PROTEIN COMPLEXES.
AB  - In this paper we investigate the distribution of myosin-9 in the cytoplasm of
      human embryonic lung fibroblasts.Using immunofluorescence, immunoprecipitation
      and western blotting, we demonstrated that myosin-9forms multimolecular complexes
      with high molecular weight tropomyosin isoforms and actin in cytoplasm ofcultured
      cells. We explored the levels of myosin-9, tropomyosin and actin in cytosol and
      cytomatrix extracts atdifferent time points after LPA addition (20 ng/ml) to
      culture medium. Cytosole extracts from human embryoniclung fibroblasts were
      subjected to co-immunoprecipitation assay with polyclonal antibodies specific toC
      terminal peptide of human myosin-9, or with monoclonal antibodies recognizing
      high molecular weight tropomyosinisoforms. The cross-immunoprecipitation method
      revealed changes in the composition of myosin-9/tropomyosin complexes under the
      action of LPA. We have observed the significant decrease in myosin-9co
      immunoprecipitated tropomyosin level immediately (1 min) after LPA addition.
      Additionally, we have foundthat LPA treatment during 1 h induces proteolytic
      degradation of myosin-9 with accumulation of 130 kDaand 40 kDa fragments in
      cytomatrix fraction. These results suggest that cytoplasmic multimolecular
      proteincomplexes containing myosin-9 and tropomyosin are involved in the
      regulation of cellular response to LPA.

PMID- 30199162
TI  - THE RESTORATION OF HYPOTHALAMIC SIGNALING SYSTEMS AS ONE OF THE CAUSES TO IMPROVE
      THE METABOLIC PARAMETERSIN BROMOCRYPTINE-TREATED RATS WITH NEONATAL MODEL OF
      DIABETES MELLITUS.
AB  - One of the approaches to correct type 2 diabetes mellitus (T2DM) and its
      complications is the use of drugbromocryptine mesylate (BCM), a selective agonist
      of type 2 dopamine receptors (DA2R). At the same time,the efficiency and the
      mechanisms of action of BCM in treatment of severe forms of T2DM are not
      currentlyunderstood. The objective was to study the effect of four-week treatment
      of male rats with neonatal T2DM modelusing BCM (300 mg/kg/day) on their metabolic
      parameters and activity of the adenylyl cyclase signalingsystem (ACSS) in the
      hypothalamus. The BCM treatment restored glucose tolerance and its utilization by
      exogenousinsulin, and normalized lipid metabolism by lowering the levels of
      triglycerides and atherogenic cholesterolincreased in T2DM. In the hypothalamus
      of BCM-treated diabetic rats, the regulation of ACSS by agonistsof type 4
      melanocortin receptor (MC4R), DA2R and 1B-subtype serotonin receptor, and the
      expression of Mc4rgene encoding MC4R were restored. Meanwhile, the BCM treatment
      had no effect on plasma insulin level andinsulin production by pancreatic b
      cells. The obtained data indicate the significant prospects of BCM to treatsevere
      forms of experimental T2DM, and show that the therapeutic potential of this drug
      includes its ability torestore the hypothalamic signaling systems sensitive to
      monoamines and peptide of the melanocortin family,which are responsible for the
      control of energy metabolism and insulin sensitivity.

PMID- 30199161
TI  - THE RELATIONSHIP BETWEEN PHYSICAL-CHEMICAL CHARACTERISTICS AND BIOLOGICAL
      ACTIVITY OF PEPTIDE 562-572 OF LUTEINIZING HORMONE RECEPTOR MODIFIED BY DECANOYL
      RADICALS AT THE N- AND C-TERMINI.
AB  - Lipophilic derivatives of peptides corresponding to the cytoplasmic regions
      associated with the G-proteincoupled receptors (GPCRs) are capable of functioning
      as an intracellular agonist. Previously, we have shownthat peptides corresponding
      to region 562-572 of luteinizing hormone receptor (LHR) and modified by
      decanoateand palmitate at the C-terminus activate adenylyl cyclase (AC) in the
      testes of rats. The stimulating effectof peptide 562-572 modified by decanoates
      at the N- and C-termini (IV) peaked at a concentration of 10(-5) Mand then
      subsequently decreased with increasing concentration. We hypothesized that this
      may be due to abilityof the peptide IV to micelle formation. To test this
      suggestion, we examined the relationship between biologicalactivity,
      hydrophobicity and ability to micelle formation for peptide IV and other acylated
      derivatives of peptide562-572 including the derivatives containing C-terminal
      decanoate (III) and palmitate (VI). It has beenshown that the stimulating effect
      of peptide IV at a concentration of 10(-5) M on AC activity in the plasma
      membranesof rat testes and ovaries is only slightly inferior to that of peptide
      VI and superior to the corresponding effectof peptide III. The effect of peptide
      IV at a concentration of 10-3 M was reduced by 20-27 % and amountedto 50-51 and
      87-88 % of that of peptides VI and III, respectively. Despite the high
      hydrophobicity, thepeptide IV had abnormally low retention time in reverse-phase
      HPLC when it was eluted from the Nucleosil C8column, even lower than that of
      unmodified peptide 562-572. However, with increasing concentration of
      trifluoroaceticacid in the eluent from 0.1 to 0.5 % causing the destruction of
      micelle-like structures, the retentiontime of the peptide IV was significantly
      increased, whereas it remained unchanged in the case of the other
      peptides.Surface tension of aqueous solution of peptide IV insignificantly
      decreased with the increase of its concentration,but then, at peptide
      concentration of 710(-6) M, the sharp decline and the plateau were found,
      whichindicates the beginning of the formation of micelles. Thus, at concentration
      of 10(-5) M and higher the peptide IVforms micelles which prevents its
      interaction with the receptor. The ability of GPCR-peptides to self
      aggregationand micelle formation should be taken into account when developing
      their membrane-active analogues.

PMID- 30199164
TI  - [Estimating Soil Iron Content Based on Reflectance Spectra].
AB  - In recent decades, the application of spectral technology in soil science is
      getting more and more attention. Soil information can be obtained quickly by
      using soil reflectance spectra to understand the physical and chemical properties
      of soil and to estimate soil iron content. In previous studies, the surface soil
      always is selected for the estimation of soil iron content by using spectroscopy.
      It needs to estimate total iron and, the different forms of soil iron is ignored,
      therefore, the estimation result is not ideal. In order to gets a different form
      of soil iron processing method of optimal model to evaluate the accuracy of
      models, as well as discuss the organic matter content and soil depth on the
      influence of different forms of soil iron estimation accuracy. A total of 160
      soil samples were collected from 20 sites in Dongtai city, Jiangsu province.
      These samples were ground to 10 meshes and 100 meshes. In the use of 8 different
      methods for the pretreatment of the same time each method will be selected by a
      variety of parameters, using partial least squares regression method to model the
      total reflection band and the total iron, free iron, amorphous iron content in
      the soil respectively, then evaluation model precision. The results showed that:
      (1) the optimal model of three kinds of soil iron was all ground to 100 meshes
      and the best pretreatment method was MSC. The prediction accuracy of total iron
      was acceptable and R2 was less than 0.6. The results of free iron and amorphous
      iron inversion were better and the R2 was 0.77 and 0.69, respectively. The errors
      were small and the models were stable. (2) Because the ferric metasilicate in
      total iron is easily affected by external environment, the organic matter and
      soil depth are of great influence on the estimate precision of total iron the
      most. But the estimation accuracy of free iron is the least affected. Because of
      the low content of amorphous iron, the estimated model is also susceptible to the
      influence of organic matter and soil depth.

PMID- 30199163
TI  - COMPARATIVE EFFECT OF FUCOIDAN FROM ALGA FUCUS VESICULOSUS AND ITS FRACTIONS,
      OBTAINED BY ANION-EXCHANGE CHROMATOGRAPHY, ON CELL LINES HeLa G-63, Hep G2 AND
      CHANG LIVER.
AB  - The aim of the present study was to compare the effect of sulfated
      fucopolysaccharides isolated from Fucusvesiculosus on cell lines HeLa G-63, Hep
      G2 and Chang liver. Native fucoidan F3 and two fractions(F3-0.5 and F3-1),
      obtained by anion-exchange chromatography, were analyzed using chemical methods
      andIR-spectroscopy. Their action on cells demonstrates that F3 and F3-1,
      characterized by higher content of sulfates,preferable location of sulfo-groups
      at C4 atom of fucose residue and low content of uronic acids, inhibit
      cellproliferation more efficiently. Human liver tumor cells Hep G2 appeared to be
      the most sensitive to fucoidantreatment whereas nonmalignant human cells Chang
      liver were the least sensitive.

PMID- 30199165
TI  - [The Application of the L-Curve Method in the Retrieval of Temperature Profiles
      Using Ground-Based Hyper-Spectral Infrared Radiance].
AB  - The thermodynamic profiles of Planetary Boundary Layer could be retrieved by
      using ground-based hyper-spectral infrared radiance. The AERIoe algorithm has a
      better performance at the dependency of initial profiles than the "onion peeling"
      method which was originally applied in the Atmospheric Emitted Radiance
      Interferometer. The regularization parameter is the key to the AERIoe algorithm,
      and the strategy for choosing the regularization parameter in the retrieval
      algorithm is based on the empirical method, which requires too much time for
      computation while the empirical method needs many iteration steps. A L-curve
      criterion is proposed to calculate the regularization parameter in AERIoe
      algorithm. The L-curve criterion is based on a log-log plot of corresponding
      values of the residual and solution norms, and the optimal regularization
      parameter corresponds to a point on the curve near the "corner" of the L-shaped
      region. Therefore, the L-curve criterion has better theoretical basis than the
      traditional empirical method. The result of retrieval experiment using the
      observed data collected at the SGP site of the year 2011 shows that, the L-curve
      method has a good performance in terms of stability, convergence and accuracy of
      the retrieval. Compared with empirical method, L-curve algorithm converges more
      quickly which saves much computation time when retrieving the temperature
      profiles. When considering the retrieval accuracy, the L-curve method has a
      better behavior at the middle and top of the boundary layer, with an improvement
      of 0.2 K of RMSE at the altitude of 1~3 km than the empirical method. Therefore,
      the L-curve algorithm has a better performance compared with the empirical method
      when choosing the regularization parameter in the retrieval of temperature
      profiles using the ground-based hyper-spectral infrared radiance.

PMID- 30199166
TI  - DEHYDRIN- STRESS PROTEINS OF BIRCH BUDS IN CONTRASTING CLIMATIC  REGIONS.
AB  - Stress proteins dehydrins have been identified using specific antibodies in buds
      silver birch (Betula pendula Roth) growing in contrasting climatic conditions of
      the regions Karelia and Central Yakutia. Dehydrins in buds of plants are
      presented in two areas: medium molecular weight (56-73 kDa) and low molecular
      weight (14-21 kDa), and 17 kDa dehydrin was detected in all studied birches. 14
      21 kDa dehydrins are the most susceptible to seasonal changes. Regardless of
      birch growing region, dehydrines 14-21 kDa show significant increase in their
      level in the autumn and winter when the trees are characterized by the highest
      frost resistances. Dehydrins have relealed intraspecific polymorphism, more
      pronounced in Yakutia plants in conditions of extreme continental climate,
      compared with Karelia, which is probably due to the peculiarities of woody plants
      to adapt to the extremely low winter temperature of the permafrost zone.

PMID- 30199167
TI  - Pharmaceutical Reference Pricing: Does It Have a Future in the U.S.?
AB  - Issue: Reference pricing is an emerging health insurance benefit design aimed at
      reducing health costs. In this model, an insurer establishes a maximum payment
      that it will contribute toward covering the price of a product or service in
      situations where there is wide price variation for therapeutically similar drugs,
      diagnostics, or procedures. Experiences to date indicate that reference pricing
      can influence patients and physicians to switch to less costly options within
      each therapeutic class, reducing overall drug prices. Goal: Describe how
      reference pricing can be and has been applied to drugs in the United States and
      compare it to more conventional pharmaceutical benefit designs such as tiered
      formularies and coinsurance. Methods: Assessment of peer-reviewed research and
      the experiences of employers that have used reference pricing. Findings and
      Conclusions: To appropriately motivate price-conscious consumer choice, reference
      pricing must include up-to-date information. Consumers and physicians must have
      access to the prices charged at different distribution sites and for different
      drugs within each therapeutic class. Reference pricing also must include
      information on quality. Several modifications to the reference pricing model
      should be made before it can be adapted to specialty drugs, and those changes
      should be informed by comparative effectiveness research.

PMID- 30199168
TI  - [Research on the Noise Reduction with Hyper-Resolution Infrared Spectrum Based on
      Improved PCV Method].
AB  - The noise reduction with observed high resolution infrared radiance is crucial to
      improve the accuracy and stability of the retrieval of thermodynamic profiles.
      When applying the principal component analysis noise filter algorithm to the
      observed radiance, the optimal number k of principal components that used in the
      algorithm was mostly calculated with the statistical and empirical method. The
      percent cumulative variance method is one of the statistical methods that have
      been commonly used to calculate k, however, the threshold of the percent
      cumulative variance was determined subjectively and arbitrarily, which limits the
      application of this method. While the empirical method need the real-time Noise
      Equivalent Spectral Radiance (NESR) to normalize non uniform noise in the
      observed data, but the real-time NESR needs the raw data of complex spectrum
      which is not easy to obtain in most cases. Aiming at the solving the problems
      above, a PCA noise filter based on the Improved PCV algorithm is proposed, of
      which the threshold is determined by iteratively calculating the difference
      between the simulated and reconstructed spectrum using different principal
      components, whereby k is determined such that the PCV is larger than the
      threshold. The new method solves the problem of arbitrary of the determination of
      k, and at the same time it doesn't need the real-time NESR to normalize the
      observed radiance. First, the impact of normalization on the noise reduction is
      analyzed using physical retrieval of temperature profiles; the result shows that
      the impact is very small, which less than the impact of calculation error of k is
      caused by normalization on the retrieval of temperature profiles. Then, the noise
      reduction of the representative radiance data which covers four quarters of 2011
      shows that, the RMSE of the retrieved temperature profile using the Improved PCV
      method is improved by 0.1 K compared to the factor indicator function method when
      the real-time NESR is not available, and it is almost the same with the latter
      when the normalization is done. Under the condition that the NESR is not
      available, the method proposed in this article could objectively and reasonably
      reduce the noise level of the ground-based high resolution infrared radiance.

PMID- 30199170
TI  - State Remedies For Costly Prescription Drugs.
AB  - (1) At least 74.7 million Americans use three or more prescription drugs in a 30
      day period. (2) Eighty percent of the U.S. public views prescription drug costs
      as "unreasonable," while 17 percent say "reasonable," according to a recent poll.
      (3) An influenza drug has a cash price of $100, but a patient with insurance may
      pay $125 because of a "gag clause" that restricts pharmacists from disclosing
      price options.

PMID- 30199169
TI  - [MOLECULAR AND CELLULAR MECHANISMS OF ANGIOGENESIS IN PHYSIOLOGICAL AND
      PATHOLOGICAL CONDITIONS].
AB  - In normal conditions vascular system is in equilibrium, the processes of
      angiogenesis and vascular regression are precisely regulated. The mechanisms
      underlying the cardiovascular and cancer diseases are the insufficient or
      excessive angiogenesis, correspondingly. Understanding the mechanisms of
      angiogenesis is necessary for the development of new approaches to cure these
      diseases. The fundamental knowledge of the vascular growth and maturation
      mechanisms formed the basis for the strategy of "therapeutic angiogenesis", which
      is one of the rapidly developing technologies in regenerative medicine in the
      world. The strategy is based on the stimulation of blood vessel growth and
      remodeling in ischemic tissues via administration of recombinant angiogenic
      factors or genetic constructs for their expression. The same knowledge of the
      mechanisms of angiogenesis is necessary in the development of new drugs aimed at
      inhibiting the vascular growth in excessive or aberrant angiogenesis, which
      escapes the physiological control in various diseases. Herein we review the
      fundamental molecular and cellular mechanisms of regulation of blood vessel
      initiation, growth, and stabilization in normal and pathological conditions.

PMID- 30199171
TI  - [Hyperspectral Analysis and Electrolyte Leakage Inversion of Creeping Bentgrass
      under Salt Stress].
AB  - Leaf electrolyte leakage is an important index of the plant cell permeability
      which plays an important role in the study of turfgrass salt stress. Traditional
      methods of measuring leaf electrolyte leakage have many disadvantages such as
      time-consuming, destroying the plants and being unable to monitor salt stress in
      large area. The aim of this study is to build a hyperspectral inversion model for
      leaf electrolyte leakage of creeping bentgrass under different salt concentration
      stresses thus to promote the application of the hyperspectral techniques in
      turfgrass salt stress monitoring. Creeping bentgrass was used in this study, and
      it was grown in water for two weeks before salt treatments. Leaves were collected
      at 7, 14 and 21 d under 0(CK), 100 and 200 mmol.L-1 NaCl respectively. The
      spectral values were gathered using Unispec-SC Spectral Analysis System (PP
      SYSTEMS,USA)before collecting grass leaves. Leaf electrolyte leakage was measured
      with electrical conductivity method. The relation and differences between salt
      treatments and spectral reflectance values were analyzed with EXCEL. Normalized
      difference vegetation index (NDVI) and difference vegetation index (DVI) were
      calculated using the spectral reflectance values. The first-order differential
      was calculated with difference method. The trilateral parameters of the blue,
      green and red rays were calculated at the meantime. The correlation analysis of
      the Leaf electrolyte leakage, spectral reflectance value, DVI and trilateral
      parameters was achieved by using EXCEL and Matlab software. Electrolyte leakage
      inversion model of the calibration set consisted of 48 high correlational
      samples, was built using unary linear regression, multivariate linear regression
      and partial least-squares regression methods. The prediction set inspection
      inversion model was established using the other 24 samples. The results showed
      that there is a positive correlation between salt stresses and 450~700 nm wave
      band. The leaf electrolyte leakage was positively associated with 450~732 nm band
      region at 0.01. The green edge amplitude and area of green edge were correlated
      with the foliar electrolyte leakage positively. Models based on partial least
      squares regression could inversion the foliar electrolyte leakage optimally. The
      calibration R2 reached to 0.681, and the validation R2 reached to 0.758. The
      calibration RMSE was 7.124, and the validation RMSE reached to 7.079. The
      inversion model made it possible to detect creeping bentgrass leaf electrolyte
      leakage under salt stress rapidly. This study also provided theoretical reference
      for monitoring the damage of other creeping bentgrass related plant species
      resulted by salt stress.

PMID- 30199172
TI  - [BASIC PHYSIOLOGICAL MECHANISMS OF HUMAN ADAPTATION TO COLD].
AB  - The article provides an overview of the literature that focuses on the main types
      of human adaptation to cold and mechanisms for increasing heat production. It is
      shown that the studies in recent years, aimed at studying the molecular
      mechanisms of adaptation to cold, confirmed the results of previous physiological
      studies have demonstrated that the major contribution to adaptive thermogenesis
      during cooling made by oxidative fibers in skeletal muscle (birds, marsupials,
      large placental and people) and brown adipose tissue (small placenta, especially
      rodents). The main sources of thermoregulatory heat generation are the
      contractile activity (thermoregulatory shivering and muscle tone), the uncoupling
      of oxidative phosphorylation and decrease in thermodynamic efficiency of the ATP
      powered pumps (ATPase), which are induced by noradrenaline and thyroid hormones
      and accompanied by an increase in the consumption of oxygen and energy
      substrates. During long-term adaptation to cold the number and activity of
      mitochondria increase to provide enhanced ATP consumption.

PMID- 30199173
TI  - [DETECTION OF OPTICAL INTRINSIC SIGNAL IN SOMATOSENSORY CORTEX OF NEONATAL RATS
      USING PRINCIPAL COMPONENT ANALYSIS].
AB  - Recordings of the intrinsic optical signal (IOS) are widely used in the
      functional imaging of the central nervous system in vivo. However, the IOS
      technique has been mainly described in the adult brain and the possibility of
      using IOS for the robust functional imaging of the immature brain and the optimal
      parameters for IOS recording and analysis in the analysis in the immature brain
      tissue remain largely unknown. Here, we show that the use of the near to infrared
      light and automatic PCA enable efficient detection of IOS in the neonatal rat
      pups' whisker-related somato- sensory cortex during the first three weeks after
      the birth. IOS detection using automatic PCA survived fourfold artificial noise
      increase in the baseline, indicating on the robustness of this approach. Thus,
      our findings indicate that IOS imaging using near infrared light and automatic
      PCA is efficient technique for the functional imaging of somatosensory cortex in
      the neonatal rats.

PMID- 30199174
TI  - Home Visiting: Improving Children's and Families' Well-Being.
AB  - (1) Studies have found a $1.80 to $5.70 return on investment for every dollar
      spent on home visiting. (2) Nearly 4 million evidence-based home visits reached
      more than 300,000 families in 2016. (3) Approximately 40 percent of U.S. counties
      have at least one home visiting agency that offers an evidence-based program.

PMID- 30199175
TI  - [Spectral Response and Inversion Models for Prediction of Total Copper Content in
      Soil of Xifanping Mining Area].
AB  - In order to solve the problem of high cost and low efficiency by using the
      traditional soil geochemical survey methods, this paper studied the simple
      detection method of soil heavy metal content with visible and near-infrared
      reflectance spectroscopy. The study collected visible and near-infrared
      reflectance spectroscopy of soil samples in Xifanping mining area; then treated
      the reflectance spectroscopy with six mathematic changes such as differentials
      and continuum removal in advance; the next step was to select characteristic
      wavelengths that were sensitive to soil copper content by using stepwise
      regression method and Pearson correlation coefficient as set of comprehensive
      characteristic variables; finally, utilized different methods and parameters of
      characteristic variable selection to build the soil total copper content models
      and tested them. Results showed that: to extract the information of copper
      content in soil, the performance of different spectral transform methods varied,
      and each spectrum transform method corresponded to its certain sensitive spectral
      ranges; the inversion models based on the integrated spectrum transform
      information were better than that based on only one kind of spectrum transform
      information; as for establishing the prediction model of soil copper content by
      using the integrated spectrum transform information, backward elimination was
      better than forward selection and stepwise selection, and when the Removal is
      0.20, the optimum model was obtained, its coefficients of determination(R(2))and
      determination coefficients of prediction(R(2)(pre))reached 0.851 and 0.830, root
      mean square error of calibration(RMSEC)and root mean square error of
      prediction(RMSEP)were 0.349 and 0.468 mg.kg(-1). The model has a good precision,
      and it provides a train of thought for the detection of other soil heavy metal
      elements with visible and near-infrared reflectance spectroscopy.

PMID- 30199176
TI  - State Safe Bicycle Passing Laws.
AB  - (1) There were 840 bicyclist traffic deaths in 2016, the highest amount since
      1991. (2) According to the Insurance Institute of Highway Safety, 45 percent of
      fatal bicycle crashes between 2008 and 2012 involved a vehicle hitting the
      bicyclist from behind or the side while traveling in the same direction. (3)
      Thirty-two states have a law requiring a motorist to provide at least 3 feet of
      space when passing a bicyclist.

PMID- 30199177
TI  - Nocturnal Atmospheric NO3 Radical Monitoring and Analysis in Beijing with Cavity
      Ring Down System .
AB  - The oxidizability of NO3 radical in the nocturnal atmosphere is comparable with
      that of diurnal OH radical. Given the importance of NO3 radical in the nocturnal
      chemical process, accurate measurement of its concentration and analysis its
      nocturnal chemical process have important significance. The article introduces
      cavity ring-down spectroscopy (CRDS) instrument which is applied to measure
      atmospheric NO3 radical. Light from a red laser diode (the wavelength is 662 nm
      and line width is 0.3 nm) is coupled on-axis into an optical cavity formed by a
      pair of high-reflectivity mirrors (R>=99.998 5%) to achieve an effective
      absorption path length of approximately 20km. And it researches nocturnal
      chemical process of NO3 radical in view of the fall and winter heavy traffic
      areas. The measurement of NO3 radical with cavity ring-down spectroscopy was
      performed in Beijing from October 29 to November 15, 2014. During the
      observation, the concentration of NO3 radical is relatively low with the maximum
      of NO3 radical concentration of 50pptv and the average of its concentration of
      approximately10 pptv. Combining of NO2, O3 and NO data, the observation results
      are analyzed. The NO3 production rates ranging from 0.04 to 1.03 pptv.s-1 were
      calculated throughout the observation, and NO3 lifetime averaged at 68 s. The NO3
      loss process in the atmosphere is further analyzed. Combining of related
      auxiliary data, the influence of different humidity as well as particulate matter
      concentrates on the atmospheric NO3 removal is researched. When atmospheric
      RH>=60% and PM2.5 concentration mainly greater than 60 MUg.m-3,the correlation
      coefficient of the logarithmic correlation between NO3 lifetime and NO2 mixing
      ratio is 0.79,NO3 is mainly removed by the indirect loss process; however, when
      atmospheric RH<=40% and the concentration of PM2.5 mainly smaller than 60 MUg.m
      3, because of the observation site is close to national highway and influenced by
      local pollution source, the direct loss process is main; When atmospheric
      40%<RH<60%, the results show the direct loss process and the indirect loss
      process both exist and cannot be ignored.

PMID- 30199194
TI  - Relationship Exploration of Chemical Content, Complex Dielectric Constant and
      Spectral Features of Rocks.
AB  - In this research, 97 pieces of rock in Xingcheng, Liaoning Province, China were
      collected to measure the spectral reflectance in 350~2 500 nm, chemical content,
      and complex dielectric constant of some samples. The absorption depths were
      calculated by using continuum- removal method. With correlation analysis method,
      two kinds of correlation curves were obtained based on the theory of spectral
      characteristics of chemical contents and the principle of dielectric constant.
      One described the relationship between chemical content and spectral absorption
      depth, and the other one represented the correlation of complex dielectric
      constant and reflectance. By summarizing curves morphological characteristics,
      several conclusions were drawn as follows: (1)There was a strong correlation
      between the chemical content (SiO2, Al2O3, CaO, K2O, MgO, burnt-loss) and
      spectral absorption depth in 1 900~2 500 nm, furthermore, at around 1 900, 2 200,
      2 300 nm and other identifying characteristic bands, local extreme maximum /
      minimum values appeared. At Fe3+ characteristic band (400~550 nm), correlation
      coefficient reached -0.406 between Fe2O3 content and absorption in igneous rock
      samples collection. Exploring the relationship between rock spectral absorption
      features and its chemical contents had a positive effect on metallogenic
      prediction and lithology identification with remote sensing image. (2)
      Reflectance and complex dielectric constant were negatively correlated totally,
      compared with the imaginary part; the real part had a better relation reached 
      0.753 at around 1 900 nm. Curves showed that there were great correlations around
      1 900 and 2 200 nm, so, our study adopted different models to simulate response
      relationships. Dielectric constant of media is one of the basic physical
      properties, and now most analyses of existing research between electromagnetic
      characteristics and dielectric constant are studied in microwave band, however,
      our research is conducted in visible and near infrared range. The conclusions
      will be useful for further exploration on dielectric characteristics and spectral
      features of rocks.

PMID- 30199195
TI  - Effect of the Infrared Absorption Properties of Sodium Nitrate with Photonic
      Crystal.
AB  - The two-dimensional photonic crystal (Ni mesh with square lattice of 10 MUm) was
      prepared and Ni film was thickened to 3 MUm by electroplating. Its optical
      properties and its influence on the infrared absorption of sodium nitrate were
      investigated. The results show that there is a transmission peak centered at 1
      450 cm-1 under normal incidence, and the peak covered the frequencies ranging
      from 1 300 to 1 500 cm-1, the antisymmetric stretching vibration of nitrate.
      Moreover, the change of absorption intensities of nitrate's antisymmetric
      stretching vibration is essentially consisting with the transmittance of photonic
      crystal. It indicates that the absorption intensity of sodium nitrate is improved
      by the modulated infrared light.

PMID- 30199196
TI  - Proposal to Reduce Adult Immunization Barriers in California.
AB  - Adult vaccination rates in the United States are consistently lower than the
      National Healthy People 2020 goals. Barriers to adult vaccination include
      inconsistency of insurance coverage of adult vaccines and difficulty in accessing
      vaccines. To help address the gap in adult access to vaccines, in 2016 the
      Department of Health Care Services--which administers the Medi-Cal program
      (California's version of Medicaid)--implemented the All Plan Letter (APL) 16-009,
      which requires coverage of recommended adult vaccines as a pharmacy benefit.
      Adult Medi-Cal patients can now receive the vaccines recommended for their age
      and underlying health conditions, and they can do so not only at a provider's
      office but also at local pharmacies, improving access and convenience. This
      policy brief recommends expanding coverage of all adult vaccines as a pharmacy
      benefit of all public and commercial insurance plans.

PMID- 30199197
TI  - [NFLUENCE OF SPONTANEOUS PARTIAL SENSORY DEPRIVATION ON MALE C57BL/6N MICE
      BEHAVIOR].
AB  - Vibrissae loss associated with the peculiarities of the intragroup social
      interaction may be an important factor affecting the animals' performance in
      various behavioral tests. To evaluate the influence of spontaneous partial
      sensory deprivation as a consequence of the barbering activity of a cage mate,
      the battery of tests was conducted in male C57Bl/6N mice. The results indicate
      that the behavior of mice without vibrissae significantly differs from control
      animals in the tube, open field, social interaction and forced swim tests. Thus,
      the present findings suggest that vibrissae conditions have to be assessed before
      the inclusion of animals into experimental groups and/or further considered in
      data analysis.

PMID- 30199198
TI  - [CHRONIC D2-RECEPTOR BLOCKADE AND BEHAVIOR OF LOW DEPRESSIVE RATS].
AB  - The article is devoted to investigation of influence of chronic D2-receptor
      blockade by haloperidol on behavior low depressive rats. It is shown that chronic
      D2-receptor blockade by haloperidol (2.5 mg/kg) causes pro-depressant effect on
      behavior of low depressive rats and leads to the formation of the depressed
      state. In control and experimental groups, identified circaseptan and
      circasemiseptan rhythms in the dynamics of the index of depression, characterized
      by a phase shift relative to each other.

PMID- 30199199
TI  - [TRANSFORMATION OF GASTROPRO- TECTIVE EFFECT OF STRESS IN PROULCEROGENIC
      CONSEGUENCE: DEVELOPMENT OF EXPERIMENTAL MODELS].
AB  - The present work was focused on the development of experimental models, in which
      we can observe the transformation of gastroprotective effect of stress into the
      proulcerogenic one. For this aim the effect chronic stress on the formation of
      indomethacin (35 mg/kg)-induced gastric erosion or cold restrain (10 or 6 
      degrees C)-induced gastric erosion was investigated in rats. For chronic stress
      rats were repeatedly restrained for 14 days daily (1 h or 4 h mild restrain or 1
      h intensive restrain) and examined on day 14. Mild restraining didn't influence
      on gastric mucosa. In case of intensive restrain, the protective effect of
      chronic stress on the gastric mucosa was found. In order to avoid the adaptation
      to the daily stressor of the same modality, we subjected the rats on a daily for
      14 days to unpredictable stressors of various modalities. Even in the case of
      strong unpredictable chronic stress we observed its gastroprotective effect if
      the indomethacin or cold restrain (10  degrees C) were used as ulcerogenic
      factors. The proulcerogenic effect of unpredictable stress was observed only if
      cold restrain at 6  degrees C was used as ulcerogenic factor. In conclusion, the
      findings again support the idea about the gastroprotective effect of stress, even
      in regards to chronic stress and demonstrate experimental models of
      transformation gastroprotective effect of stress to ulcerogenic one.

PMID- 30199200
TI  - [ROLE OF MAST CELLS IN BRONCHIAL CONTRACTION IN NONALLERGIC OBSTRUCTIVE LUNG
      PATHOLOGY].
AB  - In model of chronic obstructive pulmonary disease induced in rats by 60-day
      intermittent exposure to nitrogen dioxide mast cells participation in the
      mechanism of bronchial smooth muscle contractile activity patterns was evaluated.
      Since the 31st day, one group of rats was inhaled with sodium cromoglycate every
      day before the nitrogen dioxide exposure to stabilize the mast cell membrane. The
      other group (control) hasn't been treated. Isometric contraction of the bronchial
      isolated preparations in response to nerve or smooth muscle stimulation were
      determined. Inhibition of mast cell degranulation and the release of endogenous
      histamine by stabilizing cell membranes prevented the development of bronchial
      smooth muscle hyperactivity caused by prolonged inhalation of nitrogen dioxide.
      It is believed that a mechanism to increase the contractile activity of the
      bronchial wall smooth muscles is mediated by activation of the transmembrane
      adenosine receptor in resident mast cells, leading to their partial degranulation
      with release of histamine, acting on the histamine Hl-receptors with the launch
      of reflex pathways through intramural ganglion neurons.

PMID- 30199201
TI  - [ANTIINFLAMMATORY AND REGENERATIVE EFFECT OF PEPTIDE THERAPY IN THE MODEL OF
      OBSTRUCTIVE LUNG PATHOLOGY].
AB  - The effect of the tetrapeptide bronchogen on the structural and functional state
      of the bronchial epithelium and inflammatory activity in the lungs was studied in
      the chronic obstructive pulmonary disease (COPD) model, created in rats by a 60
      day intermittent exposure to nitrogen dioxide. The cell composition and cytokine
      enzyme profile of bronchoalveolar lavage fluid (BALF), the content of secretory
      immunoglobulin A and surfactant protein B in BALF were determined. Following the
      course of peptide treatment the decreased activity of neutrophilic inflammation
      with the normalization of cellular composition and profile of pro-inflammatory
      cytokines and enzymes in the bronchoalveolar space was observed. The structure of
      bronchial epithelium, disturbed during formation of COPD model, was restored and
      accompanied by restoration of its functional activity as evidenced by an increase
      of secretory immunoglobulin A (local immunity marker) and surfactant protein B,
      responsible for reducing the alveolar surface tension.

PMID- 30199202
TI  - [HR AND DURATION OF ECG ELEMENTS OF AN ADULT DURING PHYSICAL EXERCISES].
AB  - The degree of heart rate (HR) and of duration PP, PT and TP elements
      electrocardiogram (ECG) before and after physical exercises (PE) depends on their
      value in the control, in healthy young girls (n = 21), aged 18.1 +/- 0.7 years,
      body weight 56.5 +/- 4.0 kg. The 300 cardiocycles by ECG at II standard lead were
      registered. Rower of PE was 1 W/kg. The growth of the HR after PE at the time of
      depolarization and repolarization (PT interval) remains practically unchanged,
      whereas the duration of the isopotential state of the myocardium (segment TP) is
      revealed. The PP intervals of long duration are shortened by 60%, low duration -
      by 30 %. The variability of PP interval in control due to the variability of the
      TP segment, in the experience of the PT interval was found.

PMID- 30199203
TI  - [CELL-MOLECULAR BASIS OFNEUROIMMUNE INTERACTIONS DURING STRESS].
AB  - The review represents a modern concept about cells-molecular basis of mechanisms
      of neuro-immune interactions, the data on the effects of destabilizing factors
      (electric pain stimulation, rotation, cold and psychoemotional stress) on the
      functioning of neurons and immune cells. It must be underlined, that under the
      stress conditions take place the alterations of ligand-receptors interactions on
      the membrane of lymphocyte. In particular the reaction of these cells to
      regulating signal - application of Interleikin-1 grow up after mild stress, but
      it falls down after an influence of severe stress factors. Special attention is
      paid to the role of the orexinergic system in mechanism of realization of CNS
      reactions to application of antigens. In the present work the possible methods of
      correction of imbalance in functional interactions between nervous and immune
      systems, caused by different destabilizing factors, are reviewed.

PMID- 30199204
TI  - [ROLE OF OPIOID RECEPTORS IN THE REGULATION OF RESISTANCE OF HEART TO IMPACT OF
      ISCHEMIA-REPERFUSION].
AB  - Activation of m-, d1-, d2- and k1-opioid receptors increases cardiac resistance
      to ischemia-reperfusion. The cardioprotective effect of opioids in many cases
      appears to be associated with the activation of the peripheral OR. However, when
      it comes to non-peptide agonists OR able to cross the blood-brain barrier, we
      cannot exclude the involvement of central opioid receptors in cardioprotection.
      Endogenous opioids are not involved in the regulation of cardiac tolerance to
      ischemia- reperfusion in non-adapted animals. Stimulation of k1- and d1-OP may
      exert delayed cardioprotective effect. Activation d- and k1-OP reduces the
      intensity of cardiomyocyte apoptosis after reperfusion. The results of studies
      related to the inotropic effect of opioids during reperfusion of the heart remain
      highly controversial.

PMID- 30199206
TI  - [Research Process on Hyperspectral Imaging Detection Technology for the Quality
      and Safety of Grain and Oils].
AB  - The quality and safety of grain and oils are related to the national nutrition
      and health safety of the public. Owing to the difficulties in operation,
      destruction, high cost, reagent pollution and other shortcomings, conventional
      detection method cannot meet the fast, non-destructive, efficient and pollution
      free requirements, which pose great difficulties in integrating with Industry
      4.0. With the development of chemometrics, hyperspectral imaging (HSI) technology
      integrates the advantages of spectroscopy and image technology to overcome the
      defects of conventional detection method, which has become the developingt trend
      of grain and oils quality testing technology. Based on many interrelated research
      papers, this paper reviews the principles of HSI and the existing research in
      quality (component determination, germination test, variety classification) and
      safety (fungal detection, pest detection) of grain and oils. Meanwhile, in order
      to promote the application and development of hyperspectral imaging technology in
      the field of grain and oils, we specially analyze the aspect of HSI including
      spectral range, chemometrics, equipment and the accuracy of model, pointing out
      the current problems and prospecting the direction and priority.

PMID- 30199205
TI  - [VESTIBULAR PROSTHETICS: CONCEPT, APPROACHES, RESULTS].
AB  - Unlike prosthetic hearing, which develops technology for more than 30 years, the
      problem of the vestibular prosthesis developed a little more than one and half
      decades. Meanwhile, the involvement of the vestibular system in ensuring the
      normal functioning of the visual, motor and other systems of the body determines
      its decisive contribution to the spatial orientation of humans and animals. In
      case of damage of the vestibular apparatus (the labyrinth), there are serious
      violations of posture control, stabilization of sight, spatial orientation,
      psychological status, that is, in the aggregate quality of human life
      deteriorates. At present, on the animals developed technology of prosthetic
      semicircular canals, sensing angular acceleration, and control eye movements in
      dynamic situations. New approaches based on the replacement of the lost natural
      vestibular afferent impulses by electrical stimulation through multichannel
      vestibular prosthesis, are successfully introducing into the clinic.

PMID- 30199207
TI  - [JUN N-TERMINAL KINASES AND THEIR PHARMACOLOGICAL MODULATION OF ISCHE-MIC AND
      REPERFUSION INJURY OF THE BRAIN].
AB  - The article reviews the literature regarding the role of c-Jun-N-terminal kinases
      (JNK) and its inhibitors in brain damage in the settings of ischemia and
      reperfusion injury. The implication of JNK in signaling mechanisms involved in
      ischemia-reperfusion-induced cerebral injury are discussed. Described effects
      associated with JNK inhibition using synthetic and natural substances in
      experimental models of ischemic and reperfusion injury of the brain. Results of
      experimental studies demonstrated that JNK represent promising therapeutic
      targets for brain protection against ischemic stroke. However, multiple
      physiologic functions of various JNK family members do not allow for the systemic
      use of non-specific JNK inhibitors for therapeutic purposes. The authors conclude
      that the continuous search for selective inhibitors of JNK3 remains an important
      task.

PMID- 30199208
TI  - [Comparison of Predicting Blueberry Firmness and Elastic Modulus with
      Hyperspectral Reflectance, Transmittance and Interactance Imaging Modes].
AB  - In this study, a imaging system with hyperspectral reflectance, transmittance and
      interactance was constructed for estimate the firmness and elastic modulus of
      blueberry. The comparisons of these three imaging modes were carried out. This
      hyperspectral system could also be applied for scattering modewhile this mode was
      not suitable for small fruit such as blueberry. The reflectance hypercubes were
      segmented with the algorithm based on the Otsu method, and the transmittance and
      interactance hypercubes were processed with the algorithms based on region
      growing approach. Subsequently, the extracted spectra were pretreated with the
      Standard Normal Variate (SNV) and Savitzky-Golay of the first derivative (Der),
      and least squares-support vector machine was applied for the establishment of the
      corresponding prediction models. The obtained results demonstrated that 
      reflectance-SNV model could predict blueberry firmness with correlation
      coefficient of prediction sample set (Rp) of 0.80 and the ratio of percent
      deviation (RPD) of 1.76 among the models using full spectra. The elastic modulus
      of blueberry was better estimated by the full transmittance spectra subjected to
      SNV pretreatment with Rp (RPD) of 0.78 (1.74) than the other models. Furthermore,
      Random Frog selection approach could to some extent reduce the uninformative
      wavelengths while increasing the prediction accuracy of the established models.
      Random Frog-Interactance-Der model achieved Rp (RPD) of 0.80 (1.83) for blueberry
      firmness, but the number of wavelength was 140. In the case of blueberry elastic
      modulus, random frog-transmittance-SNV showed the relatively superior performance
      compared to the other models, with Rp (RPD) of 0.82 (1.83) and fewer wavelength
      number of 20.

PMID- 30199209
TI  - [EFFECT OF ESTRADIOL ON INSULIN SIGNAL TRANSMISSION].
AB  - Reduced insulin sensitivity plays an important role in the pathogenesis of type
      II diabetes. Est-radiol increases sensitivity to insulin. Effect of estradiol may
      be due to the influence on gene expression, level of proteins or activity of
      insulin signaling pathway components and insulin target proteins. Effect of
      estradiol also may be due to the influence on GLUT4 translocation in the cell
      membrane. Effects of estradiol on insulin receptor substrate,
      phosphatidylinositol-3-kinase, protein kinase B, glucose transporter type 4,
      glucose-6-phosphatase most often examined. In this paper, data on the influence
      of estradiol on insulin sensitivity in liver, adipose and muscle tissues
      systematized in order to identify promising areas of research and new targets for
      pharmacological correction of insulin resistance.

PMID- 30199210
TI  - [COMPARISON OF CHRONIC ANTICONVULSANT ACTIVITY AND SAFETY OF IEM-2062, SODIUM
      VALPROATE AND ME-MANTINE IN THE PENTYLENETETRAZOL KINDLING MODEL IN RATS].
AB  - IEM-2062 [1-(6-aminohexylamino)-1-phenylcyclohexyl dihydrochloride], causing a
      combined block NMDA and AMPA receptors, after chronic oral administration in
      doses, respectively, 0.3 and 3 mg/kg, induce maximal anticonvulsant effect in the
      pentylenetetrazol kindling rats because decrease the number of completely
      kindling rats by 100 %, and also decrease in 2.5-3.3 times the average severity
      of clonic-tonic kindling seizures. IEM-2062 causes significant anticon- 299
      vulsant effects in the widest range of doses, 1-48 mg/kg, which is 24-22 times
      more than that of memantine (12-20 mg/kg) and sodium valproate (100-200 mg/kg).
      Sodium valproate and memantine cause significant disturbances of locomotor
      activity in the "open field" test in doses causing maximal anticonvulsant effect
      in the kindling rats. At the same time IEM-2062 cause disturbance of locomotor
      activity only in very high dose of 92 mg/kg, which exceeds in 30.7 times the dose
      causing the maximum anticonvulsive effect in the kindling rats. Thus, IEM-2062
      reduces the severity of kindling seizures in 1.7-1.9 times stronger than sodium
      valproate and memantine and also by 30.7 times is safer than sodium valproate and
      memantine.

PMID- 30199211
TI  - [CYTOKINES SECRETION BY SPLENOCY-TES IN RESPONSE TO MICE F1 (C57BL/6XDBA/2)
      BEHAVIOR IN ENVIRONMENTS OF VARYING COMPLEXITY].
AB  - We study the dependence of the mitogen-induced cytokine secretion by splenocytes
      from the character of the behavior of F1 (C57BL/6XDBA/2) mice in environments
      with different degrees of spatial complexity: simple in the form of home box,
      enriched box and maze. Suppression of in-terleukins IL-2, IL-4, IL-6 and IL-10
      expression, regardless of their structural and functional properties, was
      observed only in an enriched environment when aggressive and neurotic
      manifestations were increased. The opposite effect in the form of significant
      increase of the productions in all studied cytokines was observed in the case of
      the stereotypical goal-directed behavior in a maze. It was supposed that
      cytokines of the splenocytes are involved in the realization of highly 307
      differentiated adaptive response of the organism due to the influence of social
      and cognitive factors, the expression of which depends on the specific
      physiological and biochemical systems.

PMID- 30199212
TI  - [NOTHROMBEL EFFECT ON THE FORMATION OF PLATELET-LEUKOCYTE COMPLEXES INDUCED BY
      THROMBIN].
AB  - The effects of the Nothrombel on the formation of platelet-leukocyte complexes
      (PLCs) induced by thrombin was studied. It was shown, that Nothrombel dose
      dependently inhibited the formation of PLCs. Its activity is higher than the
      activity of the comparison compounds Aspirin. The half maximal effective
      concentration (EC50) for Nothrombel is 1.75 mMol/mL, for Aspirin is much more
      than 2.5 mMol/mL. The inhibition mechanism of the PLCs formation by Nothrombel
      caused by the ability of this drug to inhibit the P-selectin translocation on the
      platelet membrane, the expression of membrane complex GPIb-IX-V, the mobilization
      of cytoplasmic calcium in platelets, as well as, apparently, its inhibitory
      effect on platelet P2Y12 purine receptors.

PMID- 30199214
TI  - [ROLES OF RATIONAL-IRRATIONAL COGNITIVE STYLES IN THE ALPHA RHYTHM REACTIVITY
      DURING CONVERGENT AND DIVERGENT THINKING].
AB  - Changes of the alpha1 and alpha2 rhythms during convergent (addition in the mind)
      and divergent (heuristic task solving) thinking due to rational and irrational
      cognitive styles were studied. It is shown that the functional activity of the
      cerebral cortex during convergent thinking was associated with rational style and
      presented in parietal low-frequency alpha1 biopotentials whereas during divergent
      thinking - with the irrational, and this effect was produced by widespread
      regional and frequency differences of alpha1 and alpha2 oscillations in posterior
      cortex. The originality of ideas correlated with the alpha desynchronization in
      the posterior cortex in the persons with high intuition, whereas the persons with
      low intuition characterized by the alpha synchronization.

PMID- 30199213
TI  - [INFLUENCE OF AGGRESSION AND RELATED PSYCHOLOGICAL CHARACTERISTICS OF ATHLETES IN
      THE FREQUENCY OF NUCLEAR VIOLATIONS IN EXFOLIATED CELLS OF THE ORAL CAVITY].
AB  - The frequency of cells with abnormal nuclear morphology (micronuclei, perinuclear
      vacuo-les, notches, protrusions, such as "tongue" and "broken egg") in the buccal
      epithelium of wrestlers on different days of the competition period was
      identified. The largest number of violations observed on the 3rd day after the
      competition. It was conducted psychological testing of athletes and it was
      determined 16 psychological characteristics associated with the aggressiveness of
      athletes. It was revealed the effect of psychoemotional state on the cytogenetic
      apparatus athletes. It was found associations of the dynamics of reactive anxiety
      athletes and frequency of nuclear aber- 327 rations. The hypothetical scheme of
      influence human aggression and related psychological characteristics of its
      genetic apparatus by neurohumoral system was constructed.

PMID- 30199215
TI  - Challenging Conventional Wisdom: Finding High-Performance Electrodes for Light
      Emitting Electrochemical Cells.
AB  - The light-emitting electrochemical cell (LEC) exhibits capacity for efficient
      charge injection from two air-stable electrodes into a single-layer active
      material, which is commonly interpreted as implying that the LEC operation is
      independent of the electrode selection. Here, we demonstrate that this is far
      from the truth and that the electrode selection instead has a strong influence on
      the LEC performance. We systematically investigate 13 different materials for the
      positive anode and negative cathode in a common LEC configuration with the
      conjugated polymer Super Yellow as the electroactive emitter and find that Ca,
      Mn, Ag, Al, Cu, indium tin oxide (ITO), and Au function as the LEC cathode,
      whereas ITO and Ni can operate as the LEC anode. Importantly, we demonstrate that
      the electrochemical stability of the electrode is paramount and that particularly
      electrochemical oxidation of the anode can prohibit the functional LEC operation.
      We finally report that it appears preferable to design the device so that the
      heights of the injection barriers at the two electrode/active material interfaces
      are balanced in order to mitigate electrode-induced quenching of the light
      emission. As such, this study has expanded the set of air-stable electrode
      materials available for functional LEC operation and also established a procedure
      for the evaluation and design of future efficient electrode materials.

PMID- 30199217
TI  - Facile Synthesis of a Terephthalic Acid-Based Organic Fluorophore with Strong and
      Color-Tunable Emission in Both Solution and Solid States for LED Applications.
AB  - Dual-state emission (DSE) fluorophores with strong photoluminescence in both
      solution and solid states have wide applications in fluorescent probes and
      photoelectric devices. However, most of the existing DSE fluorophores involve
      complex synthetic strategies or only one or two emission colors in the solid
      state, which may hinder their practical applications. Herein, we report a facile
      and effective strategy to fabricate a kind of novel adjustable DSE fluorophore
      TPAA-Cu based on the small molecule terephthalic acid (TPA) and ascorbic acid
      (AA) with CuCl2 as the catalyst. Not only can the TPAA-Cu solution emit blue,
      blue-green, and yellow colors depending upon the pH of solution, but also it
      shows reversible pH-tunable fluorescence colors. More importantly, corresponding
      TPAA-Cu solid fluorophores with blue, blue-green, and yellow colors can also be
      obtained with the quantum yields of 16.3, 26.7, and 29.6%, respectively.

PMID- 30199216
TI  - Facile Synthesis toward the Optimal Structure-Conductivity Characteristics of the
      Argyrodite Li6PS5Cl Solid-State Electrolyte.
AB  - The high Li-ion conductivity of the argyrodite Li6PS5Cl makes it a promising
      solid electrolyte candidate for all-solid-state Li-ion batteries. For future
      application, it is essential to identify facile synthesis procedures and to
      relate the synthesis conditions to the solid electrolyte material performance.
      Here, a simple optimized synthesis route is investigated that avoids intensive
      ball milling by direct annealing of the mixed precursors at 550  degrees C for 10
      h, resulting in argyrodite Li6PS5Cl with a high Li-ion conductivity of up to 4.96
      * 10-3 S cm-1 at 26.2  degrees C. Both the temperature-dependent alternating
      current impedance conductivities and solid-state NMR spin-lattice relaxation
      rates demonstrate that the Li6PS5Cl prepared under these conditions results in a
      higher conductivity and Li-ion mobility compared to materials prepared by the
      traditional mechanical milling route. The origin of the improved conductivity
      appears to be a combination of the optimal local Cl structure and its homogeneous
      distribution in the material. All-solid-state cells consisting of an 80Li2S-20LiI
      cathode, the optimized Li6PS5Cl electrolyte, and an In anode showed a relatively
      good electrochemical performance with an initial discharge capacity of 662.6 mAh
      g-1 when a current density of 0.13 mA cm-2 was used, corresponding to a C-rate of
      approximately C/20. On direct comparison with a solid-state battery using a solid
      electrolyte prepared by the mechanical milling route, the battery made with the
      new material exhibits a higher initial discharge capacity and Coulombic
      efficiency at a higher current density with better cycling stability.
      Nevertheless, the cycling stability is limited by the electrolyte stability,
      which is a major concern for these types of solid-state batteries.

PMID- 30199218
TI  - Highly Transparent Polyethylcyanoacrylates from Approved Eco-Friendly Fragrance
      Materials Demonstrating Excellent Fog-Harvesting and Anti-Wear Properties.
AB  - Superglue monomers belong to a family of cyanoacrylates that are known for their
      very rapid polymerization upon contact with moist surfaces. Their biodegradation
      and low toxicity make them attractive as medical and veterinary adhesives.
      Although the fast-acting polymerization characteristics have been successfully
      utilized to design nanoscale polymeric particles that can carry drugs or other
      inorganic nanoparticles, it constitutes a significant drawback if one desires to
      produce other forms of functional biodegradable acrylics, such as coatings,
      sheets, or nanocomposites. This is because rapid polymerization in air creates
      highly porous and brittle structures. Here, we address this drawback by reporting
      a simple and inexpensive method of fabricating highly transparent (>92%)
      polyethylcyanoacrylate (PECA) coatings by dispersing the monomer in a fragrance
      classified green liquid, cyclopentanone. The resulting transparent coatings were
      hydrophilic but with slippery wetting characteristics, suitable as efficient fog
      harvesting templates. Furthermore, another fragrance liquid, benzyl alcohol, is
      introduced as a plasticizer and co-solvent to overcome its brittleness while
      retaining its transparency. The same plasticized monomer solutions, dispersing
      low concentrations of graphene (<0.5 wt %), were allowed to self-assemble on
      stainless steel surfaces, forming low-friction and anti-wear dry lubricants by
      decreasing the steel friction coefficient and wear rate by 6- and 10-fold,
      respectively.

PMID- 30199219
TI  - Macrocycle-Encircled Polynuclear Metal Clusters: Controllable Synthesis,
      Reactivity Studies, and Applications.
AB  - Macrocyclic ligands have been extensively applied to recognize single metal ions
      with high selectivity and good affinity based on the size-match principle. The
      resulting metal-macrocycle complexes play a significant role in mimicking the
      function of natural metal ion carriers and understanding and reproducing the
      catalytic activity of metalloenzymes. Because of the known macrocyclic effect,
      those single metal-macrocycle adducts often show an enhanced kinetic and
      thermodynamic stability in comparison with their open-chain analogues. By virtue
      of such extraordinary coordination properties of macrocyclic ligands, it is
      expected that larger macrocycles with multiple coordination sites could properly
      act as an outer scaffold to direct the formation of multiatom species inside,
      such as polynuclear metal cluster aggregates, whose assembly may largely depend
      on the template positioning of coordinative atoms in the macrocyclic ring. Thus,
      the employment of polydentate macrocyclic ligands may provide a convenient tool
      to access polynuclear metal clusters in a controllable way. In this Account, we
      review our studies of the metal ion binding process of a class of polydentate
      macrocyclic ligands, azacalixpyridines (Py[ n]s), and the application of Py[ n]s
      as an outer template to direct the controllable synthesis of polynuclear metal
      clusters. Our investigations revealed that Py[ n]s show a significant cooperative
      coordination effect in the metal ion binding process that facilitated the easy
      formation of a polymetallic assembled structure. Taking advantage of the
      cooperative coordination effect and the tunable and highly fluxional conformation
      of Py[ n]s, we laid our focus on control of the nuclearity number by tuning the
      size of Py[ n]s and the adoption of Py[ n]s with different anionic centers in
      metal cluster synthesis. As an important example for application, this new
      established macrocycle-directed method has been employed to achieve a variety of
      metal-cluster-centered capsule, rotaxane, catenane, polygon, and other
      supramolecular assemblies. Furthermore, a cluster-to-cluster transformation
      inside the cavity of Py[ n]s is presented to showcase the use of the acquired
      metal cluster-macrocycle complexes to achieve unconventional metal cluster
      entities. With regard to the application of the newly synthesized macrocycle
      encircled metal clusters, examples of the fabrication of functional materials and
      catalysts are presented. With the assistance of Py[ n]s, a bulk-to-cluster-to
      nanoparticle transformation of silver sulfide (Ag2S) and silver halides (AgX) has
      been conducted to produce a series of nonstoichiometric silver sulfide and halide
      nanoparticles. The resulting Ag-S nanoparticle material with a high Ag/S ratio,
      which is inherited from the Py[ n]-protected polysilver sulfide clusters, has a
      large energy gap relative to conventional Ag2S nanoparticles. Moreover, the
      nonstoichiometric silver halide nanoparticles can act as a new kind of
      electrocatalyst for the chlorine evolution reaction, showing excellent
      selectivity and high catalytic efficiency. Overall, in this Account we try to
      highlight the application of polydentate macrocycles as an outer template to
      guide the synthesis of polynuclear metal clusters in a controllable manner. This
      unique synthesis will provide a new avenue to access unconventional metal
      clusters of different metal kinds and diverse anionic centers, which are expected
      to have promising and significant applications in many interdisciplinary areas of
      chemistry.

PMID- 30199220
TI  - Preferential Neighboring Substitution-Triggered Full Visible Spectrum Emission in
      Single-Phased Ca10.5- xMg x(PO4)7:Eu2+ Phosphors for High Color-Rendering White
      LEDs.
AB  - Manipulating the distribution of rare-earth activators in multiple cation
      lattices can achieve versatile color output for single-phased phosphor-converted
      white light-emitting diodes (LEDs). However, successful cases are barely
      reported, owing to the uncertain distribution of rare-earth activators and the
      special combination of three primary colors for white LEDs. Herein, we took
      whitlockite beta-Ca3(PO4)2 as a multiple cation lattice host to manipulate the
      redistribution of Eu2+ activators, and the surprising Mg2+-guided redistribution
      of Eu2+ activators among different Ca sites is reported for the first time to
      regulate the photoluminescence (PL) behavior in series Ca10.5- xMg x(PO4)7:Eu2+
      phosphors. The preferential neighboring substitution of smaller Mg2+ cations in
      Ca(5) and Ca(4) sites triggers a discontinuous evolution of local structure along
      c axis and induces covalent variable Ca(1), Ca(2), and Ca(3) cation sites for the
      accommodation of Eu2+ activators. The unique optical feature enables the single
      phased Ca9.75Mg0.75(PO4)7:Eu2+ phosphor-converted white LED to exhibit quite high
      color-rendering index Ra (85) and R9 (91) values. The preferential neighboring
      cation substitution reported here can not only manipulate the migration of Eu2+
      activators among different cation sites for tunable PL properties, but also carve
      out a new way for next-generation high-quality solid-state lighting.

PMID- 30199221
TI  - Advanced Fuel Cell Based on Perovskite La-SrTiO3 Semiconductor as the Electrolyte
      with Superoxide-Ion Conduction.
AB  - A solid oxide fuel cell's performance is largely determined by the ionic
      conducting electrolyte. A novel approach is presented for using the semiconductor
      perovskite La0.25Sr0.75TiO3 (LST) as the electrolyte by creating surface
      superionic conduction, and the authors show that the LST electrolyte can deliver
      superior power density, 908.2 mW cm-2 at just 550  degrees C. The prepared LST
      materials formed a heterostructure, including an insulating core and a superionic
      conducting surface layer. The rapid ion transport along the surfaces or grain
      boundaries was identified as the primary means of oxygen ion conduction. The fuel
      cell-induced phase transition was observed from the insulating LST to a super O2-
      conductivity of 0.221 S cm-1 at 550  degrees C, leading to excellent current and
      power outputs.

PMID- 30199222
TI  - Unexpected Effect of Electrode Architecture on High-Performance Lithium-Sulfur
      Batteries.
AB  - In the past years, considerable efforts have been devoted to the deliberate
      synthesis of nanosulfur in various hosts with sophisticated structures to improve
      the performance of lithium-sulfur batteries (LSBs) and reveal the structure
      property relationship. It is taken for granted that these elaborate sulfur
      nanostructures are well maintained in the ultimate electrode after the
      traditional mixing and coating method. Herein, we, for the first time, reveal the
      unexpected sulfur structure deterioration in nanosulfur/graphene composites
      during the electrode preparation using the traditional method because of the long
      term neglected dissolution-recrystallization effect of sulfur in solvents.
      Consequently, compared with binder-free three-dimensional graphene/sulfur
      electrodes, the milled graphene/sulfur electrodes exhibit much worse
      electrochemical performance. On the basis of this, we further propose a facile
      and universal graphene oxide-assisted assembly method to avoid the dissolution
      recrystallization of sulfur, by which binder-free three-dimensional
      ethylenediamine-functionalized graphene/sulfur (3DEFGS) electrodes have been
      successfully prepared. The 3DEFGS electrodes with a high areal sulfur loading of
      ~6 mg cm-2 exhibit an ultrahigh initial capacity of 1394 mA h g-1 at 0.1 C, an
      excellent rate performance with a capacity of 796 mA h g-1 at 4 C, and superior
      long-term cycling stability (885 mA h g-1 after 500 cycles at 1 C), which are
      among the best performances achieved by all reported LSB cathodes with high areal
      sulfur loadings.

PMID- 30199223
TI  - Development of Adenosine A2A Receptor Antagonists for the Treatment of
      Parkinson's Disease: A Recent Update and Challenge.
AB  - Parkinson's disease (PD) is a neurodegenerative disease with significant unmet
      medical needs. The current dopamine-centered treatments aim to restore motor
      functions of patients without slowing the disease progression. Long-term usage of
      these drugs is associated with diminished efficacy, motor fluctuation, and
      dyskinesia. Furthermore, the nonmotor features associated with PD such as sleep
      disorder, pain, and psychiatric symptoms are poorly addressed by the dopaminergic
      treatments. Adenosine receptor A2A antagonists have emerged as potential
      treatment for PD in the past decade. Here we summarize the recent work (2015
      2018) on adenosine receptor A2A antagonists and discuss the challenge and
      opportunity for the treatment of PD.

PMID- 30199224
TI  - Ring-Opening of Indoles: An Unconventional Route for the Transformation of
      Indoles to 1 H-Pyrazoles Using Lewis Acid.
AB  - An unusual transformation of indoles to pyrazoles via an aromatic ring-opening
      strategy has been developed. The salient feature of this strategy involves the C2
      N1 bond opening and concomitant cyclization reaction of the C2?C3 bond of the
      indole moiety with the tosylhydrazone, which proceeds under transition-metal and
      ligand free conditions. This ring-opening functionalization of indoles provides a
      wide scope of differently substituted pyrazoles.

PMID- 30199225
TI  - Collective Shape Actuation of Polymer Double Emulsions by Solvent Evaporation.
AB  - We demonstrate that the shape actuation of water-in-oil-in-water double emulsion
      droplets can be achieved by controlling solvent evaporation in a model system,
      where the oil phase consists of hydrophobic homopolymer/amphiphilic block
      copolymer/solvent. A gradient of interfacial tension is created in the polymer
      shell, which drives significant deformation of the droplets in constant volume.
      The deformed droplets recover to their initial shape spontaneously, and shape
      actuation of droplets can be further tuned by osmotic pressure. Our model system
      provides a new prototype for developing shape-responsive droplets in a solvent
      environment.

PMID- 30199227
TI  - Understanding Structure-Property Relationships in All-Small-Molecule Solar Cells
      Incorporating a Fullerene or Nonfullerene Acceptor.
AB  - To investigate the influence of donor molecule crystallinity on photovoltaic
      performance in all-small-molecule solar cells, two dithieno[2,3- d:2',3'- d']
      benzo[1,2- b:4,5- b']dithiophene (DTBDT)-based small molecules, denoted as DTBDT
      Rho and DTBDT-S-Rho and incorporating different side chains, are synthesized and
      characterized. The photovoltaic properties of solar cells made of these DTBDT
      based donor molecules are systemically studied with the [6,6]-phenyl-C71-butyric
      acid methyl ester (PC71BM) fullerene acceptor and the O-IDTBR nonfullerene
      acceptor to study the aggregation behavior and crystallinity of the donor
      molecules in both blends. Morphological analyses and a charge carrier dynamics
      study are carried out simultaneously to derive structure-property relationships
      and address the requirements of all-small-molecule solar cells. This study
      reveals exciton decay loss driven by large-scale phase separation of the DTBDT
      molecules to be a crucial factor limiting photocurrent generation in the all
      small-molecule solar cells incorporating O-IDTBR. In the all-small-molecule
      blends, DTBDT domains with dimensions greater than 100 nm limit the exciton
      migration to the donor-acceptor interface, whereas blends with PC71BM exhibit
      homogeneous phase separation with smaller domains than in the O-IDTBR blends. The
      significant energy losses in nonfullerene-based devices lead to decreased Jsc and
      fill factor values and unusual decrease in Voc values. These results indicate the
      modulation of phase separation to be important for improving the photovoltaic
      performances of all-small-molecule blends. In addition, the enhanced molecular
      aggregation of DTBDT-S-Rho with the alkylthio side chain leads to higher degrees
      of phase separation and unfavorable charge transfer, which are mainly responsible
      for the relatively low photocurrent when using DTBDT-S-Rho compared with that
      when using DTBDT-Rho. On the other hand, this enhanced molecular aggregation
      improves the crystallinity of DTBDT-S-Rho and results in its increased hole
      mobility.

PMID- 30199226
TI  - Self-Assembled High Quality CsPbBr3 Quantum Dot Films toward Highly Efficient
      Light-Emitting Diodes.
AB  - Full inorganic cesium lead halide perovskites (IOPs) are regarded as attractive
      candidates for light-emitting diodes (LEDs) by their excellent luminescent
      conversion. However, unsatisfactory efficiency and stability are still the main
      drawbacks that hinder the commercialization progress of perovskite LEDs (PeLEDs).
      Here, we report an extremely uniform and flat CsPbBr3 film composing of self
      assembly core-shell structured quantum dots (SCQDs) based on one-step precursor
      coating. The QDs size in the CsPbBr3 film is around 4.5 nm (smaller than the Bohr
      radius), which significantly confines injected carriers and leads to a ultrahigh
      exciton binding energy ( Eb) of 198 meV. In addition, unfavorable surfacial
      defects are dramatically passivated by a thin surfacial-capping layer composed of
      long-chain ammonium groups (phenylalanine bromide, PPABr), resulting in an
      ultralow nonradiative recombination rate. Consequently, the CsPbBr3 SCQDs film
      presents a high photoluminescence quantum yield (PLQY) of 85%. It enables the
      resulting green PeLEDs to deliver a recorded external quantum efficiency (EQE)
      over 15% with ideal operational stability. Furthermore, the developed CsPbBr3
      SCQDs film also demonstrates promising potential in multifunctional lighting
      sources such as flexible and smart devices.

PMID- 30199228
TI  - All Polymer Solution Processed Electrochromic Devices: A Future without Indium
      Tin Oxide?
AB  - The growing range of applications for optoelectronic and electrochromic devices
      (ECDs) encourages the search for materials combining high electrical conductivity
      with optical transparency. Next generation transparent conducting electrodes
      (TCEs) are required to be inexpensive, lightweight, scalable, and compatible with
      flexible substrates to trigger innovations towards supporting sustainable living
      and reducing energy consumption. Here we show that PEDOT:PSS can be solution
      processed using blade coating and subsequently post-treated with nitric and
      acetic acid to raise its conductivity above 2000 S cm-1 with a film transparency
      of ~95%. A combined grazing-incidence wide angle X-ray scattering, atomic force
      microscopy, and thickness analysis of the film indicates that the removal of
      excess insulating PSS- inducing reordering is the critical parameter for the
      claimed conductivity increase. We then investigate the impact of replacing indium
      tin oxide electrodes with PEDOT:PSS in ECDs. While electrochromic contrast and
      optical memory are comparable for devices constructed with both electrode
      materials, differences in switching kinetics are explored by comparing internal
      resistances, ion diffusion, and charging effects in the polymer films extracted
      by electrochemical impedance spectroscopy. While all these ideas are described
      based on a battery-type ECD configuration, these concepts are easily transferable
      to other types of redox-active devices.

PMID- 30199229
TI  - Coordination-Assisted Polymerization of Mesoporous Cobalt Sulfide/Heteroatom
      (N,S)-Doped Double-Layered Carbon Tubes as an Efficient Bifunctional Oxygen
      Electrocatalyst.
AB  - It is a critical challenge to construct efficient precious-metal-free
      bifunctional oxygen electrocatalysts for fuel cell and metal-air batteries via
      structural and component engineering. Herein, a one-dimensional mesoporous double
      layered tubular structure, where Co9S8 nanocrystals are incorporated into
      nitrogen, sulfur codoped carbon, is successfully synthesized via the coordinated
      assisted polymerization and sacrificial template methods. The double-layered
      tubular structure provides for a large electrochemically active surface area and
      promotes fast mass transfer. Cobalt oxides/oxyhydroxides, which are evolved from
      the sulfides during the catalytic processes, as the main active sites efficiently
      catalyze the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER),
      in cooperation with the Co-N-C and heteroatom-induced active sites. Hence, it
      demonstrates excellent bifunctional electrocatalytic activity with the
      overvoltage between the OER potential at 10 mA cm-2 ( E10) and ORR half-wave
      potential ( E1/2) of 0.707 V, which is superior to most of precious-metal-free
      bifunctional oxygen electrocatalysts reported recently, as well as the state-of
      art Pt/C and RuO2 catalysts.

PMID- 30199230
TI  - REP 2139: Antiviral Mechanisms and Applications in Achieving Functional Control
      of HBV and HDV Infection.
AB  - Nucleic acid polymers (NAPs) are broad spectrum antiviral agents whose antiviral
      activity in hepatitis B virus (HBV) infection is derived from their ability to
      block the release of the hepatitis B virus surface antigen (HBsAg). This
      pharmacological activity blocks replenishment of HBsAg in the circulation,
      allowing host mediated clearance. This effect has important clinical significance
      as the clearance of circulating HBsAg dramatically potentiates the ability of
      immunotherapies to restore functional control of HBV infection which persists
      after antiviral therapy is removed. These effects are reproducible in preclinical
      evaluations and in several clinical trials that have evaluated the activity of
      the lead NAP, REP 2139, in monotherapy and in combination with immunotherapy in
      hepatitis B e antigen (HBeAg) negative and HBeAg positive HBV infection and also
      in HBeAg negative HBV/hepatitis D virus (HDV) coinfection. These antiviral
      effects of REP 2139 are achieved in the absence of any direct immunostimulatory
      effect in the liver and also without any discernible direct interaction with
      viral components. The search for the host protein interaction with NAPs that
      drives their antiviral effects is ongoing, and the interaction targeted by REP
      2139 within infected cells has not yet been elucidated. This article provides an
      updated review of available data on the effects of REP 2139 in HBV and HDV
      infection and the ability of REP 2139-based combination therapy to achieve
      functional control of HBV and HDV infection in patients.

PMID- 30199231
TI  - Novel and Traditional Organophosphate Esters in House Dust from South China:
      Association with Hand Wipes and Exposure Estimation.
AB  - The present study investigated the occurrence of 20 organophosphate esters (OPEs)
      in house dust from 51 South China homes and the risks of human exposure to OPEs
      via two pathways: dust ingestion and hand-to-mouth contact. In addition to
      several traditional OPEs, five out of six novel OPEs, including bisphenol A
      bis(deiphenyl phosphate) (BPA-BDPP), t-butylphenyl diphenyl phosphate (BPDPP),
      cresyl diphenyl phosphate (CDP), isodecyl diphenyl phosphate (IDDPP), and
      resorcinol-bis(diphenyl)phosphate (RDP), were frequently detected in house dust
      (median concentration: 59.7-531 ng/g). Eight of the 20 target OPEs were
      frequently detected in hand wipes collected from adults and children ( n = 51 and
      31, respectively), which in combination (referred to as Sigma8OPEs) had a median
      mass of 76.9 and 58.9 ng, respectively. Increasing dust concentrations of
      Sigma8OPEs or three individual substances among these eight OPEs, including
      tris(1-chloro-2-propyl) phosphate (TCIPP), tris(1,3-dichloro-2-propyl) phosphate
      (TDCIPP), and triphenyl phosphate (TPHP), were strongly associated with their
      levels in children's hand wipes ( p < 0.05 in all cases). By contrast, in adults'
      hand wipes only TPHP exhibited a marginally significant association with dust
      concentrations ( p = 0.04). Levels of Sigma8OPEs in hand wipes from children, but
      not adults, were inversely influenced by hand washing frequency ( p = 0.002),
      while indoor temperature was inversely associated with hand wipe levels of
      Sigma8OPEs from both children and adults ( p = 0.01 and 0.002, respectively).
      Exposure estimation suggests that hand-to-mouth contact represents another
      important pathway in addition to dust ingestion and that children are subjected
      to higher OPE exposure than adults.

PMID- 30199232
TI  - Coupling Electron Capture Dissociation and the Modified Kendrick Mass Defect for
      Sequencing of a Poly(2-ethyl-2-oxazoline) Polymer.
AB  - With increasing focus on the structural elucidation of polymers, advanced tandem
      mass spectrometry techniques will play a crucial role in the characterization of
      these compounds. In this contribution, synthesis and analysis of methyl-initiated
      and xanthate-terminated poly(2-ethyl-2-oxazoline) using Fourier transform ion
      cyclotron resonance (FT-ICR) mass spectrometry (MS) was achieved. Electron
      capture dissociation (ECD) produced full end group characterization as well as
      backbone fragmentation including complete sequence coverage of the polymer. A
      method of fragment ion characterization is also presented with the use of the
      high-resolution-modified Kendrick mass defect plots as a means of grouping
      fragments from the same fragmentation pathways together. This type of data
      processing is applicable to all tandem mass spectrometry techniques for polymer
      analysis but is made more effective with high mass accuracy methods. ECD FT-ICR
      MS demonstrates its promising role as a structural characterization technique for
      polyoxazoline species.

PMID- 30199233
TI  - Single-Crystal to Single-Crystal Uptake of Volatile Solids and Associated
      Chromatic Response in a Porous Metallocycle.
AB  - Guest molecules have been absorbed into crystals of a metallocyclic host by
      sublimation of volatile solids at room temperature. The guest exchanges are
      accompanied by color changes. Since the crystals remain intact, evidence of guest
      inclusion could be obtained using single-crystal X-ray diffraction. The results
      are also supported by thermogravimetric analysis (TGA), powder X-ray diffraction
      (PXRD), Fourier transform infrared spectroscopy (FT-IR), and ultraviolet-visible
      spectroscopy (UV-vis).

PMID- 30199234
TI  - Analysis of Interleukin 8 Secretion by a Stem-Cell-Derived Human-Intestinal
      Epithelial-Monolayer Platform.
AB  - In vitro models of the human intestinal epithelium derived from primary stem
      cells are much needed for the study of intestinal immunology in health and
      disease. Here, we describe an intestinal monolayer cultured on a porous membrane
      with accessible basal and apical surfaces for assay of intestinal cytokine
      production in response to stimuli. The system was composed of a differentiated,
      confluent epithelial monolayer derived from human primary stem cells obtained
      from small or large intestine. Interleukin 8 (IL-8) and monocyte chemoattractant
      protein 1 (MCP-1) were the most abundant inflammatory cytokines produced by the
      intestinal epithelium. The epithelium from all five tested regions of the
      intestine preferentially secreted into the apical reservoir of the monolayer,
      with a 26-fold greater concentration of IL-8 present in the apical reservoir of
      the colonic monolayer relative to that in the basal reservoir. Upon application
      of tumor-necrosis factor alpha (TNF-alpha) to the basal surface of the colonic
      monolayer, the IL-8 concentration significantly increased in the basal, but not
      the apical, reservoir. A dose-dependent elevation of IL-8 in the basal reservoir
      was observed for TNF-alpha-stimulation of the monolayer but not for an organoid
      based platform. To demonstrate the utility of the monolayer system, 88 types of
      dietary metabolites or compounds were screened for their ability to modulate IL-8
      production in the basal reservoir of the intestinal monolayer in the absence or
      presence of TNF-alpha. No dietary metabolite or compound caused an increase in IL
      8 in the basal reservoir in the absence of TNF-alpha. After addition of TNF-alpha
      to the monolayer, two compounds (butyrate and gallic acid) suppressed IL-8
      production, suggesting their potential anti-inflammatory effects, whereas the
      dietary factor forskolin significantly increased IL-8 production. These results
      demonstrate that the described human-intestinal-monolayer platform has the
      potential for assays and screening of metabolites and compounds that alter the
      inflammatory response of the intestine.

PMID- 30199235
TI  - Efficient Synthesis of Glycosaminoglycan Analogs.
AB  - Glycosaminoglycans (GAGs) are among the most complex, biologically active
      polysaccharides in nature. The complexity of GAGs greatly impedes their
      synthesis, thus complicating the structure-property studies that are so necessary
      for us to understand the roles of GAGs in natural processes, in pathogen
      invasion, and to understand how to develop effective interventions, for example,
      to prevent undesired GAG hijacking by pathogens. Total synthesis of GAG oligomers
      from monosaccharide building blocks is useful, but incredibly labor-intensive,
      expensive, and inefficient. In this study, we report a regiospecific synthetic
      route to two types of designed GAG analogs by chemical modification of
      commercially available, inexpensive cellulose acetate. Cellulose acetate was
      first brominated, followed by azide displacement to introduce azides as the GAG
      amine precursors. The resulting 6-N3 cellulose acetate was then saponified to
      liberate 6-OH groups. Subsequent oxidation of the liberated primary hydroxyl
      groups to carboxyl groups was smoothly effected by a TEMPO-catalyzed process.
      Finally, the azides were reduced to amines using an aqueous process, new to
      polysaccharide chemistry, employing reduction by dithiothreitol (DTT).
      Alternatively, another process new to polysaccharide chemistry could be employed
      to convert most of the azides to acetamido groups (mimicking those present, for
      example, in native hyaluronic acid) by reduction with thioacetic acid. All the
      intermediates and products were characterized by 1H NMR, 13C NMR, and FT-IR
      spectroscopy. This synthetic route provides access to GAG analogs that will be of
      great interest for exploring structure-property relationships in various
      biomedical applications.

PMID- 30199236
TI  - Enhanced Activity and Enantioselectivity of Henry Reaction by the Postsynthetic
      Reduction Modification for a Chiral Cu(salen)-Based Metal-Organic Framework.
AB  - Metal-organic frameworks (MOFs) imbedded privileged molecular catalysts are of
      particular interest due to their higher catalytic activities derived from the
      MOFs pore/channel confinement effect, improved lifetime through eliminating
      intermolecular deactivation pathway, and the recyclability based on their
      heterogeneity. In this work, a 3D chiral metallosalen-based MOF
      [Cd2(Cu(salen))(DMF)3].DMF.3H2O (1) with a 1D open channel was synthesized and
      characterized by single-crystal X-ray diffraction and other physicochemical
      methods. Upon postsynthetic reduction modification with NaBH4, the conversion
      from imino to amino group on salen cores of 1 generates the reduction product 2
      with a more flexible chiral group and more alkaline backbone, meanwhile still
      maintaining the original porous framework. 2 can be used as an efficient
      heterogeneous catalyst for the asymmetric Henry reaction with broad substrate
      applicability and exhibits higher activity and enantioselectivity (ee up to 98%)
      compared with the unreduced 1. Note that 2 can accelerate the Henry reaction of
      pyridine-2-carboxaldehyde possessing a potential coordination atom with excellent
      ee value; however, the homogeneous counterpart does not. In addition, the bulky
      aldehydes show a decrease in activity but almost the same enantioselectivity with
      an increase in the molecular size of substrates as a result of the chiral
      confinement effect of 2, indicating the size-dependent selectivity. To the best
      of our knowledge, this is the highest enantioselectivity for asymmetric Henry
      reaction catalyzed by MOF-based catalysts.

PMID- 30199237
TI  - NMR-Based Determination of pH, Free of Electrodes and Reference Compounds.
AB  - A novel method was elaborated, and a set of 1H NMR-pH indicator molecules was
      selected to develop an NMR-based pH determination method, which does not need any
      glass or other electrodes or any separate reference compound, being thus devoid
      of the usual acid and base errors of the glass and combined electrodes. The
      method utilizes organic compounds of accurately known basicity and two or more
      carbon-bound protons, whose chemical shifts respond differently to pH changes.
      Accurate determination of protonation constants in pH extrema was achieved by the
      method of relative basicities using compounds of sequentially incremented
      protonation constants. The entire pH scale can be covered by six indicator
      molecules. The method was developed for two ionic strengths, 1.00 and 0.15 M.

PMID- 30199238
TI  - Control of Hexamerization, Assembly, and Excluded Strand Specificity for the
      Sulfolobus solfataricus MCM Helicase.
AB  - A growing body of evidence supports a steric exclusion and wrapping model for DNA
      unwinding in which hexameric helicases interact with the excluded single-stranded
      DNA (ssDNA) in addition to the encircled strand. Interactions with the excluded
      ssDNA have been shown to be mediated primarily by electrostatic interactions, but
      base stacking with surface-exposed tyrosine residues is an alternative
      hypothesis. Here, we mutated several external tyrosine and positively charged
      residues from full-length Sulfolobus solfataricus MCM along the proposed path of
      excluded strand binding and assessed their impact on DNA unwinding. Four of the
      five tyrosine residues had significant decreases in their level of unwinding, and
      one, Y519A, located within the alpha/beta-alpha linker region of the C-terminal
      domain, had the most severe perturbation attributed to the disruption of
      hexamerization. The Y519 mutant exhibits an enhanced and stabilized secondary
      structure that is modulated by temperature, binding DNA with a higher apparent
      affinity and suggesting a pathway for hexameric assembly. Hydrogen/deuterium
      exchange coupled to mass spectrometry was used to map deuterium uptake
      differences between wild-type and Y519A apo structures highlighting global
      differences in solvent accessible areas consistent with altered quaternary
      structure. Two of the five electrostatic mutants had significantly reduced levels
      of DNA unwinding and combined with previous mutations better define the exterior
      binding path. The importance of the electrostatic excluded strand interaction was
      confirmed by use of morpholino DNA substrates that showed analogous reduced
      unwinding rates. These results better define the hexameric assembly and influence
      of the excluded strand interactions in controlling DNA unwinding by the archaeal
      MCM complex.

PMID- 30199239
TI  - Mobility Analysis of Proteins by Charge Reduction in a Bipolar Electrospray
      Source.
AB  - Analysis of large electrosprayed biopolymers by electrical mobility alone is
      greatly facilitated by reducing their charge to unity. Here, we combine within a
      single chamber positive aqueous electrospray (ES), producing multiply charged
      protein cations, with negative methanolic ES, yielding small singly charged
      anions. Use of a 100 mM triethylammonium formate buffer in both solutions yields
      very small drops. The two sprays are decoupled electrostatically by an interposed
      50% transparent, grounded metallic grid. This screen is readily crossed by the
      ions, resulting in substantial charge reduction. In spite of the grid, the
      aqueous spray is easily destabilized by the presence of anions in the positive ES
      region. Nonetheless, practical ES stabilization is achieved by using relatively
      small capillary tips (~15 MUm) in the positive emitter. Protein peaks obtained
      are as narrow as those previously reported via charge reduction with a
      radioactive Ni-63 source. Controlling the position of the negative ES permits
      spanning the full range of charge states, from high natural values to
      predominantly singly charged ions, even for large proteins such as immunoglobulin
      G (~150 kDa).

PMID- 30199240
TI  - Inductive Coupling and Flow for Increased NMR Sensitivity.
AB  - A device is proposed to enhance the NMR sensitivity of slowly relaxing nuclei,
      taking advantage of a controlled solution flow within a microfluidic circuit and
      microsized NMR detection. Unlike our previous work ( Carret et al. Anal. Chem.
      2017 , 89 ( 5 ), 2995 - 3000 ), this setup can be easily installed on any
      commercial NMR probehead as it uses induction between the commercial antenna and
      the microcoil. Such a system leads to a significant gain in sensitivity per time
      unit for slowly relaxing nuclei while preserving the capabilities of the host
      probehead.

PMID- 30199241
TI  - Cage Encapsulated Gold Nanoparticles as Heterogeneous Photocatalyst for Facile
      and Selective Reduction of Nitroarenes to Azo Compounds.
AB  - A discrete nanoscopic organic cage (OC1R) has been synthesized from a
      phenothiazine based trialdehyde treating with chiral 1,2-cyclohexanediamine
      building block via dynamic imine bond formation followed by reductive amination.
      The cage compound has been characterized by several spectroscopic methods, which
      advocate that OC1R has trigonal prismatic shape formed via [2 + 3] self-assembled
      imine condensation followed by imine reduction. This newly designed cage has
      aromatic walls and porous interior decorated with two cyclic thioether and three
      vicinal diamine moieties suitable for binding gold ions to engineer the
      controlled nucleation and stabilization of ultrafine gold nanoparticles (AuNPs).
      The functionalized confined pocket of the cage has been used for the controlled
      synthesis of AuNPs with narrow size distribution via encapsulation of Au(III)
      ions. Inductively coupled plasma mass spectrometric (ICP-MS) analysis revealed
      that the composite Au@OC1R has very high (~68 wt %) gold loading. In distinction,
      reduction of gold salts in absence of the cage yielded structureless
      agglomerates. The fine-dispersed cage anchored AuNPs (Au@OC1R) have been finally
      used as potential heterogeneous photocatalyst for very facile and selective
      conversion of nitroarenes to respective azo compounds at ambient temperature in
      just 2 h reaction time. Exceptional chemical stability and reusability without
      any agglomeration of AuNPs even after several cycles of use are the potential
      features of this material. The composite Au@OC1R represents the first example of
      organic cage supported gold nanoparticles as photocatalyst.

PMID- 30199242
TI  - Relative Quantification of Phosphatidylcholine sn-Isomers Using Positive Doubly
      Charged Lipid-Metal Ion Complexes.
AB  - Phosphatidylcholines are the major phospholipid component of most eukaryotic cell
      membranes. Phosphatidylcholines have been shown to actively participate in
      regulatory and metabolic processes. Dysfunctional metabolic processes have been
      linked to human disease and can result in altered phosphatidylcholine structural
      features, such as permutation of fatty acid connectivity. Assignment and relative
      quantitation of structural isomers that arise from fatty acid permutation on the
      phosphatidylcholine backbone, so-called sn-isomers, is difficult with routine
      tandem mass spectrometry or with liquid chromatography without authentic
      standards. In this work, we report on the observation that phosphatidylcholines
      form abundant doubly charged metal ion complexes during electrospray ionization
      (ESI) and show that these complexes can be used to assign fatty acid moieties,
      relatively quantify sn-isomers in MS2 experiments, and mass spectrometrically
      separate phosphatidylcholines from other phospholipid classes in positive ion
      mode. Addition of Fe2+ salts (20 mol %) to ESI spray solutions affords highly
      abundant doubly charged metal ion phosphatidylcholine complexes (~110% of
      protonated compounds) and allows sensitive fragment ion detection (limit of
      detection = 100 pM). Higher energy collisional dissociation, collision-induced
      dissociation, and ultraviolet photodissociation of doubly charged complexes yield
      two fragment ions for every fatty acid moiety. The latter two tandem MS methods
      preferentially yield sn-2 associated product ions enabling relative sn-isomer
      quantification. The analytical utility of doubly charged phosphatidylcholine
      metal ion complexes is demonstrated for polar lipid extracts, including extracts
      from diabetes type 1 and type 2 mouse models, and sn-isomer abundances are
      derived.

PMID- 30199243
TI  - Flexible Continuous Particle Beam Switching via External-Field-Reconfigurable
      Asymmetric Induced-Charge Electroosmosis.
AB  - Continuous sample switching is an essential process for developing an integrated
      platform incorporating multiple functionality with applications typically ranging
      from chemical to biological assays. Herein we propose a unique method of external
      field-reconfigurable symmetry breaking in induced-charge electroosmosis above a
      simple planar bipolar electrode for continuous particle beam switching. In the
      proposed system, the spatial symmetry of a nonlinear electroosmotic vortex flow
      can be artificially reordered to achieve an asymmetric electrically floating
      electrode polarization by regulating the configurations of the external ac
      signals, thus contributing to flexible particle beam switching. This switching
      system comprises an upstream flow-focusing region where particles are prefocused
      into a beam on the bipolar electrode by transversal electroconvective mass
      transfer, and a deflecting region in which the resulting particle beam is
      deflected to generate a steerable lateral displacement to enter the desired
      region via the action of an asymmetric polarization-induced reshapable
      electroosmotic flow stagnation line in a controllable background field gradient.
      A lateral particle displacement on the order of hundreds of micrometers can be
      achieved in a deterministic manner by varying the voltage, frequency, and inlet
      flow rate, thereby enabling multichannel particle switching. Furthermore, the
      versatility of the switching mechanism is extended by successfully accomplishing
      fluorescent nanoparticle beam switching, yeast cell switching, five-outlet
      particle switching, and simultaneous switching of two particle types. The
      proposed switching approach provides a promising technique for flexible
      electrokinetic sample preconcentration prior to any subsequent analysis and can
      be conveniently integrated with other micro/nanofluidic components into a
      complete functional on-chip platform owing to its simple electrode structure.

PMID- 30199244
TI  - Dinitrogen Fixation by Vanadium Complexes with a Triamidoamine Ligand.
AB  - Dinitrogen-divanadium complexes with triamidoamine ligands, 1-3, were synthesized
      and characterized by resonance Raman, UV-vis, and NMR spectroscopy and elemental
      and X-ray structure analyses. X-ray structure analyses reveal that all three of
      the complexes have a dimeric structure with a MU-N2 ligand (N-N bond length 1.200
      1.221 A). Resonance Raman and NMR spectra of 1-3 in solution show that these
      complexes maintain a dimeric structure in benzene and toluene solutions. 15N NMR
      spectra of 1 and 3 have peaks assignable to MU-N2 ligands at 33.4 and 27.6 ppm,
      respectively, but 2 does not have a similar peak under the same conditions. In
      51V NMR spectra, the peaks of vanadium ions were observed at -173.3, -143.8, and 
      240.2 ppm, respectively, which are in a higher magnetic field region in
      comparison to those of dinitrogen-divanadium complexes reported previously. The
      structure and electronic properties of 1 are supported by DFT calculations.
      Additionally, all complexes react with excess amounts of M[C10H8] (M = Na, K) and
      the proton sources HOTf, HCl, and [LutH]OTf (Lut = 2,6-dimethylpyridine) to
      produce ammonia without hydrazine. The ammonia produced was evaluated as an
      ammonium salt by 1H and 15N NMR spectroscopy. The yield of NH3 produced in the
      reaction of 1 with Na[C10H8] and HOTf under N2 was 151% (per V atom).

PMID- 30199245
TI  - Copper Mobilization and Immobilization along an Organic Matter and Redox Gradient
      Insights from a Mofette Site.
AB  - Mofettes (natural geogenic CO2 exhalations) represent excellent sites to study
      the behavior of Cu in soils and the co-occurrence of different mobilization and
      immobilization processes since they exhibit both a gradient in redox conditions
      (oxic to permanently anoxic) and in soil organic matter (SOM; low to high
      contents). Soil and pore water samples from an 18 m-transect over a mofette
      showed a complex behavior of Cu, with highest mobility in the transition between
      oxic and anoxic conditions. Cu(II) sorption experiments on SOM-rich topsoil
      revealed that Cu mobility under oxic conditions was confined by adsorption to SOM
      while in the oxygen-free mofette center reduction and precipitation of sulfides
      was the dominating Cu-sequestering process. In transition areas with low amounts
      of oxygen (<10%), there was no mineral precipitation, instead high dissolved-to
      soil organic carbon ratios strongly increased Cu mobility. Our results show that
      low stability of SOM formed under oxygen-limited conditions leads to increased Cu
      mobility unless sulfur-reducing conditions cause Cu sequestration by sulfide
      precipitation. The interplay of these (im)mobilization processes and especially
      the unexpectedly high mobility under suboxic conditions have to be considered
      when assessing Cu mobility along spatial or temporal redox gradients, e.g., at
      contamination sites or periodically flooded soils.

PMID- 30199247
TI  - Electrostatic Effects on the Stability of Peptide Radicals.
AB  - We explored the influence of external electric fields (EEFs) on the stability of
      a glycine dipeptide model radical using high-level quantum chemical methods.
      Remotely located ions (Cl-/Na+) are used to implement EEF effects. The effects of
      these ions are reproduced using background point charges and oriented EEFs.
      Remote charges as far as 900 pm from the Calpha radical center can be
      significantly stabilizing or destabilizing as a function of their relative
      orientation. The magnitude of these effects is also strongly dependent on the
      distance between the radical center and the charge location. After examining the
      strengths and weaknesses of some frequently used quantum mechanics methods in
      describing these effects properly, a comparison is made on the stability of
      dipeptide radicals bearing protonable or deprotonable side chains. In this group,
      the stability of the respective Calpha radicals mainly depends on the preferred
      orientation of the charge-carrying side chain.

PMID- 30199246
TI  - Nucleophilic Addition to Singlet Diradicals: Homosymmetric Diradicals.
AB  - Experiments have demonstrated that nucleophiles can attack singlet diradicals to
      generate bonded, closed-shell addition products. Here, we present a molecular
      orbital analysis for this reaction, focusing on the addition of nucleophiles to
      homosymmetric diradicals. We show that beginning with the Salem-Rowland molecular
      orbital description of homosymmetric diradicals, a continuous progression from
      open-shell diradical to closed-shell addition product occurs during the reaction
      via a gradual evolution of orbital and configuration interaction coefficients.
      This theoretical framework is supported by high-level multireference computations
      (CASPT2, EOM-SF-CCSD(dT)) using the addition of chloride to p-benzyne to generate
      a p-chlorophenyl anion as a case study. When using levels of theory that include
      dynamic correlation, the reaction is predicted to be barrierless. No abrupt
      switch from diradical to closed-shell species happens during the mechanism, but
      rather a gradual decrease in diradical character occurs as the nucleophile
      approaches the radical center before ultimately transforming into the closed
      shell anion. The overarching conclusion from this work is that there are no
      electronic impediments of any kind, deriving from orbital symmetry or from any
      other source, that exist for the addition of nucleophiles to homosymmetric
      singlet diradicals.

PMID- 30199248
TI  - Ability of IR and NMR Spectral Data to Distinguish between a Tetrel Bond and a
      Hydrogen Bond.
AB  - The placement of a nucleophile X along the R-CH3 axis of a methyl group can be
      described as either a trifurcated H bond or as a tetrel bond between C and X.
      Quantum calculations of the vibrational and NMR spectral features of a number of
      systems are used to provide a framework by which to distinguish between the
      presence of a tetrel or H bond. Both cationic and neutral methyl-containing Lewis
      acids (SMe3+, NMe4+, SMe2) are paired with both neutral and anionic Lewis bases
      (NH3, OH2, OCHNH2, OCH3-, OH-, HCOO-). As the base is moved away from the R-CH3
      axis of the Lewis acid (tetrel bond) toward a position along a CH axis (CH...X H
      bond), the methyl stretching frequencies shift to the red, and the bending modes
      shift to the blue. This modification in the geometry also causes the methyl C
      atom NMR chemical shielding to increase, while the methyl H atom is progressively
      deshielded. These changes are of sufficiently large magnitude that they should
      provide a means to distinguish these two bonding situations from one another.

PMID- 30199250
TI  - Mechanistic Insights into the Nickel-Catalyzed Cross-Coupling Reaction of
      Benzaldehyde with Benzyl Alcohol via C-H Activation: A Theoretical Investigation.
AB  - With the aid of density functional theory (DFT) calculations, mechanistic
      investigations have been carried out for the nickel-catalyzed dehydrogenative
      cross-coupling reaction of benzaldehyde with benzyl alcohol in the presence of N
      heterocyclic carbene (NHC) ligand. The overall Ni(0)/Ni(II) catalytic cycle
      consists of four basic steps: ligand exchange, oxidative addition, hydrogen
      transfer, and reductive elimination. Considerable interests are paid on detecting
      the transition state of the rate-determining step, with particular emphasis on
      the structural and electronic properties, together with clarifying the important
      roles of external oxidant and hydrogen acceptor. The hydrogen transfer process in
      the oxidative addition step is rate-determining in the whole catalytic cycle,
      which is accomplished by C-Ha (active Ha) activation without generating the high
      energy nickel hydride intermediate. Such process could be understood as the
      direct hydrogen transfer, instead of general concerted oxidative addition to low
      valent transition metal. The analysis of the bond distances, electron
      distributions, and orbital interactions highlights the direct hydrogen transfer
      mechanism. Furthermore, by exploring the influences from the electronic effect of
      different substrates on the reaction energy barriers, the  a,a,a
      trifluoroacetophenone could accelerate the direct hydrogen transfer with low
      activate energy.

PMID- 30199249
TI  - Introduction of a Methyl Group Curbs Metabolism of Pyrido[3,4- d]pyrimidine
      Monopolar Spindle 1 (MPS1) Inhibitors and Enables the Discovery of the Phase 1
      Clinical Candidate N2-(2-Ethoxy-4-(4-methyl-4 H-1,2,4-triazol-3-yl)phenyl)-6
      methyl- N8-neopentylpyrido[3,4- d]pyrimidine-2,8-diamine (BOS172722).
AB  - Monopolar spindle 1 (MPS1) occupies a central role in mitosis and is one of the
      main components of the spindle assembly checkpoint. The MPS1 kinase is an
      attractive cancer target, and herein, we report the discovery of the clinical
      candidate BOS172722. The starting point for our work was a series of pyrido[3,4-
      d]pyrimidine inhibitors that demonstrated excellent potency and kinase
      selectivity but suffered from rapid turnover in human liver microsomes (HLM).
      Optimizing HLM stability proved challenging since it was not possible to identify
      a consistent site of metabolism and lowering lipophilicity proved unsuccessful.
      Key to overcoming this problem was the finding that introduction of a methyl
      group at the 6-position of the pyrido[3,4- d]pyrimidine core significantly
      improved HLM stability. Met ID studies suggested that the methyl group suppressed
      metabolism at the distant aniline portion of the molecule, likely by blocking the
      preferred pharmacophore through which P450 recognized the compound. This work
      ultimately led to the discovery of BOS172722 as a Phase 1 clinical candidate.

PMID- 30199251
TI  - Phosphonamidate Prodrugs of a Butyrophilin Ligand Display Plasma Stability and
      Potent Vgamma9 Vdelta2 T Cell Stimulation.
AB  - Small organophosphorus compounds stimulate Vgamma9 Vdelta2 T cells if they serve
      as ligands of butyrophilin 3A1. Because the most potent natural ligand is ( E)-4
      hydroxy-3-methyl-but-2-enyl diphosphate (HMBPP), which is the last intermediate
      in bacterial biosynthesis of isoprenoids that is not found in mammalian
      metabolism, activation of these T cells represents an important component of the
      immune response to bacterial infections. To identify butyrophilin ligands that
      may have greater plasma stability, and clinical potential, we have prepared a set
      of aryl phosphonamidate derivatives (9a-i) of the natural ligand. Testing of
      these new compounds in assays of T cell response has revealed that this strategy
      can provide compounds with high potency for expansion of Vgamma9 Vdelta2 T cells
      (9f, EC50 = 340 pM) and interferon gamma production in response to loaded K562
      cells (9e, EC50 = 62 nM). Importantly, all compounds of this class display
      extended plasma stability ( t1/2 > 24 h). These findings increase our
      understanding of metabolism of butyrophilin ligands and the structure-activity
      relationships of phosphonamidate prodrugs.

PMID- 30199252
TI  - Nucleophilic Addition to Singlet Diradicals: Heterosymmetric Diradicals.
AB  - In the preceding paper, we examined the addition of nucleophiles to homosymmetric
      diradicals and showed that the reaction occurs with no symmetry restrictions or
      other electronic impediments. In this work, we examine the addition of
      nucleophiles to heterosymmetric diradicals, by using the addition of chloride to
      m-dehydrotoluene as a case study. Using CASPT2 and density functional theory
      calculations, we show that the addition of chloride to m-dehydrotoluene is
      predicted to be barrierless at the asymptotic limit if Cs symmetry is broken, and
      the reaction is allowed to proceed through a nonplanar geometry. A nonplanar
      cyclic allene acts as the transitioning structure between open-shell and closed
      shell species for the addition of chloride, with a continuous and smooth changing
      of the wave function by the evolution of orbital and configuration interaction
      coefficients, such that there is no abrupt switch from diradical to closed-shell
      species along the reaction coordinate. The overall conclusion from our analysis
      is that both homosymmetric and heterosymmetric diradicals can undergo reaction
      with closed-shell reagents without a barrier, and one cannot rule out the direct
      addition of nucleophiles to diradicals when considering the reaction mechanism.

PMID- 30199253
TI  - Identification of the First PPARalpha/gamma Dual Agonist Able To Bind to
      Canonical and Alternative Sites of PPARgamma and To Inhibit Its Cdk5-Mediated
      Phosphorylation.
AB  - A new series of derivatives of the PPARalpha/gamma dual agonist 1 allowed us to
      identify the ligand ( S)-6 as a potent partial agonist of both PPARalpha and
      gamma subtypes. X-ray studies in PPARgamma revealed two different binding modes
      of ( S)-6 to the canonical site. However, ( S)-6 was also able to bind an
      alternative site as demonstrated by transactivation assay in the presence of a
      canonical PPARgamma antagonist and supported from docking experiments. This
      compound did not activate the PPARgamma-dependent program of adipocyte
      differentiation inducing a very less severe lipid accumulation compared to
      rosiglitazone but increased the insulin-stimulated glucose uptake in 3T3-L1
      adipocytes. Finally, ( S)-6 inhibited the Cdk5-mediated phosphorylation of
      PPARgamma at serine 273 that is currently considered the mechanism by which some
      PPARgamma partial agonists exert antidiabetic effects similar to
      thiazolidinediones, without showing their typical side effects. This is the first
      PPARalpha/gamma dual agonist reported to show this inhibitory effect representing
      the potential lead of a new class of drugs for treatment of dyslipidemic type 2
      diabetes.

PMID- 30199254
TI  - Effect of pH on Size and Internal Structure of Poly(propylene imine) Dendrimers:
      A Molecular Dynamics Simulation Study.
AB  - The behavior of poly(propylene imine) dendrimers at three different solution pH
      is investigated through molecular dynamics (MD) simulations in explicit solvent.
      MD simulations provide an insight into the conformational properties of
      dendrimers via the evaluation of their size, shape, radial density distribution,
      static structure factor, and scattering intensity. The size of the dendrimer
      increases from high solution pH to low pH. The internal structure of the
      dendrimer is quantified in terms of the radial atomic density profile and the
      terminal amine group density distribution. While the radial atomic density
      distribution shifts away from the core of the dendrimer with decreasing pH, a
      significant degree of back-folding of the outer generations is observed at high
      pH for higher generations of growth. Results from the structure factor and
      scattering intensity indicate two types of conformational transitions: (i) as a
      function of the solution pH, where the dendrimer evolves from an expanded
      structure at low pH to a highly compact one at high pH (except for higher
      generations), and (ii) with increasing generations, where the open structure of
      the dendrimer at lower generations transforms to a compact structure at higher
      generations at both high and low pH, characterized by a change in the fractal
      dimension.

PMID- 30199255
TI  - Extraction of Silicone Uncrosslinked Chains at Air-Water-Polydimethylsiloxane
      Triple Lines.
AB  - Silicone elastomers such as polydimethylsiloxane (PDMS) are convenient materials
      routinely used in laboratories that combine ease of preparation, flexibility,
      transparency, and gas permeability. However, these elastomers are known to
      contain a small fraction of uncrosslinked low-molecular-weight oligomers, the
      effects of which are not completely understood, particularly when used in contact
      with liquids. Here, we show that triple lines involving air, water, and PDMS
      elastomers are responsible for the contamination of water-air interfaces by
      uncrosslinked silicone oligomers through a capillarity-induced extraction
      mechanism. We investigate both the case of static and moving contact lines and
      study various geometries ranging from partially immersed PDMS plates to water
      droplets or air bubbles deposited on PDMS plates, all involving air-water
      elastomer triple lines. We demonstrate experimentally that the contamination
      timescale is strikingly shorter for moving contact lines than in the static case.
      Eventually, we propose a simple poroelastic model capturing the main features of
      contamination observed in experiments.

PMID- 30199256
TI  - Irilone from Red Clover ( Trifolium pratense) Potentiates Progesterone Signaling.
AB  - The use of botanical dietary supplements is becoming increasingly popular for the
      alleviation of hormonal-based conditions such as hot flashes, premenstrual
      syndrome, and fertility. Estrogen and progesterone receptors (ER and PR) play an
      essential role in these processes. However, despite the fact that many therapies
      used to alleviate gynecological conditions act through PR-mediated mechanisms,
      few studies have investigated or identified any herbal natural product components
      that act on this receptor. In the current study, we used a progesterone response
      element (PRE)-luciferase (Luc) reporter assay to identify four phytoprogestins
      present in a standardized red clover ( Trifolium pratense) extract. We found that
      the component irilone (1) potentiated the effect of progesterone in both
      endometrial and ovarian cancer cell lines. In these cancers, progesterone action
      is generally associated with positive outcomes; thus the potentiating effect of 1
      may provide entirely new strategies for enhancing progesterone signaling as a
      means of mitigating conditions such as fibroids and endometriosis. Formononetin
      (3) and biochanin A (4) exhibited mixed agonist activity, while prunetin (2)
      acted only as an antagonist. Collectively, these results suggest that the effects
      of red clover extract repeatedly observed in cultured cells and the inverse
      correlation between risk of various cancers and flavonoid intake may be due, in
      part, to altered progesterone signaling.

PMID- 30199257
TI  - Terpenoids from Euphorbia pedroi as Multidrug-Resistance Reversers.
AB  - The phytochemical study of Euphorbia pedroi led to the isolation of a new
      tetracyclic triterpenoid with an unusual spiro scaffold, spiropedroxodiol (1),
      along with seven known terpenoids (2-8). Aiming at obtaining compounds with
      improved multidrug-resistance (MDR) reversal activity, compound 8, an ent
      abietane diterpene, was derivatized by introducing nitrogen-containing and
      aromatic moieties, yielding compounds 9-14. The structures of compounds were
      characterized by detailed spectroscopic analysis, including 2D NMR experiments
      (COSY, HMQC/HSQC, HMBC, and NOESY). Compounds 1-14 were evaluated for their MDR
      reversing activity on human ABCB1 gene transfected mouse lymphoma cells (L5178Y
      MDR) through a combination of functional and chemosensitivity assays. The natural
      compounds 1-8 were further evaluated on resistant human colon adenocarcinoma
      cells (Colo320), and, additionally, their cytotoxicity was assessed on
      noncancerous mouse (NIH/3T3) and human (MRC-5) embryonic fibroblast cell lines.
      While spiropedroxodiol (1) was found to be a very strong MDR reversal agent in
      both L5178Y-MDR and Colo320 cells, the chemical modifications of helioscopinolide
      E (8) at C-3 positively contributed to increase the MDR reversal activity of
      compounds 10, 12, and 13. Furthermore, in combination assays, compounds 1 and 7
      14 enhanced synergistically the cytotoxicity of doxorubicin. Finally, by means of
      molecular docking, the key residues and binding modes by which compounds 1-14 may
      interact with a murine P-glycoprotein model were identified, allowing additional
      insights on the efflux modulation mechanism of these compounds.

PMID- 30199258
TI  - DBU-Promoted Dynamic Kinetic Resolution in Rh-Catalyzed Asymmetric Transfer
      Hydrogenation of 5-Alkyl Cyclic Sulfamidate Imines: Stereoselective Synthesis of
      Functionalized 1,2-Amino Alcohols.
AB  - Dynamic kinetic resolution (DKR)-driven asymmetric transfer hydrogenation of 5
      alkyl cyclic sulfamidate imine produces the corresponding sulfamidate with
      excellent levels of diastereo- and enantioselectivity by employing a HCO2H/DBU
      mixture as the hydrogen source in the presence of the Noyori-type chiral Rh
      catalyst at room temperature for 1 h. In this process, DKR was induced by DBU
      promoted rapid racemization of the substrate. Stereoselective transformations of
      the resulting cyclic sulfamidates to functionalized enantiomerically enriched 1,2
      amino alcohol and chiral amine substances are also described.

PMID- 30199259
TI  - Synergistic Catalysis-Enabled Thia-Aza-Prins Cyclization with DMSO and
      Disulfides: Entry to Sulfenylated 1,3-Oxazinanes and Oxazolidines.
AB  - A novel synergistically catalyzed thia-aza-Prins cyclization of alkenylamines
      with disulfides is reported, rendering the first synthesis of sulfenylated 1,3
      oxazinanes and oxazolidines in good to high yields. Importantly, DMSO serves
      simultaneously as a reaction medium and a surrogate for formaldehyde. Mechanistic
      studies provide evidence that actions of CuBr2 and in situ formed sulfinic acids
      as a Lewis acid and Bronsted acid catalyst, respectively, synergistically
      catalyze these cyclization processes.

PMID- 30199260
TI  - Total Syntheses of Aromatic Abietane Diterpenoids Utilizing Advances in the
      Pummerer Rearrangement.
AB  - The first total syntheses of triptobenzene T, vitexifolin C, 4- epi-triptobenzene
      L, triptobenzene L, and nepetaefolin F have been accomplished through an
      enantioselective, common intermediate approach and have enabled the confirmation
      and/or establishment of the absolute stereochemistry of each natural product
      synthesized. Application of three new and/or underutilized Pummerer reaction
      pathways proved critical to the synthetic work. A proline sulfonamide-catalyzed
      Yamada-Otani reaction was used to access the highly functionalized cyclohexane A
      ring core, including the C10 all-carbon quaternary stereocenter. Additionally,
      the importance of the A ring unsaturation for controlling the stereoselectivity
      during the C4 alkylation is showcased.

PMID- 30199261
TI  - Cinchona-Diaminomethylenemalononitrile Organocatalyst for the Highly
      Enantioselective Hydrophosphonylation of Ketones and Enones.
AB  - The use of diaminomethylenemalononitrile (DMM) organocatalyst to promote the
      challenging 1,2-hydrophosphonylation of simple ketones and enones, which are also
      called alpha,beta-unsaturated ketones, is proposed and validated. This reaction
      provided the corresponding chiral alpha-hydroxy phosphonates in high to excellent
      yields and with enantioselectivity up to 96% ee.

PMID- 30199262
TI  - Axial-Chiral Biisoquinoline N, N'-Dioxides Bearing Polar Aromatic C-H Bonds as
      Catalysts in Sakurai-Hosomi-Denmark Allylation.
AB  - The design, synthesis, and evaluation of axial-chiral biisoquinolines bearing
      polar aromatic C-H bonds as Lewis base catalysts are reported. Lewis bases
      containing the 3,5-bis(trifluoromethyl)phenyl group were found to be
      significantly more enantioselective for a wider range of substrates than those
      bearing aromatic residues that are not strongly electron-deficient in the
      allylation of aldehydes with allyltrichlorosilane. Also, optically pure 3,3'
      dibromo-1,1'-biisoquinoline N, N'-dioxide that has not been previously reported
      was synthesized as a common catalyst precursor to facilitate the study.

PMID- 30199263
TI  - Dynamics of Charge Transfer and Multiple Exciton Generation in the Doped Silicon
      Quantum Dot-Carbon Nanotube System: Density Functional Theory-Based Computation.
AB  - We use the Boltzmann transport equation (BE) to study time evolution of a
      photoexcited state, including phonon-mediated exciton relaxation, multiple
      exciton generation (MEG), and energy-transfer processes. BE collision integrals
      are derived using Kadanoff-Baym-Keldysh many-body perturbation theory (MBPT)
      based on density functional theory (DFT) simulations, including exciton effects.
      We apply the method to a nanostructured p- n junction composed of a 1 nm hydrogen
      terminated Si quantum dot (QD) doped with two phosphorus atoms (Si36P2H42)
      adjacent to the (6, 2) single-wall carbon nanotube (CNT) with two chlorine atoms
      per two unit cells adsorbed to the surface. We find that an initial excitation
      localized on either the QD or CNT evolves into a transient charge-transfer (CT)
      state where either electron or hole transfer has taken place. The CT state
      lifetime is about 40 fs. Also, we study MEG in this system by computing internal
      quantum efficiency (QE), which is the number of excitons generated from an
      absorbed photon during relaxation. We predict efficient MEG starting at 3 Eg ?
      1.5 eV and with QE reaching QE = 1.65 at about 5 Eg, where Eg ? 0.5 eV is the
      lowest exciton energy, i.e., the gap. However, we find that including energy
      transfer and MEG effects suppresses CT state generation.

PMID- 30199264
TI  - Pummerer Cyclization Revisited: Unraveling of Acyl Oxonium Ion and Vinyl Sulfide
      Pathways.
AB  - Two viable pathways (vinyl sulfide and acyl oxonium ion) for the Pummerer
      cyclization have been unraveled that expand the reaction scope and capabilities.
      Use of Bronsted- enhanced Lewis acidity was key to realization of the vinyl
      sulfide pathway, whereas selective complexation of the sulfur lone pair
      facilitated the unprecedented acyl oxonium ion pathway. Preliminary mechanistic
      investigations support these hypotheses. A range of substrates have been explored
      to understand the reaction parameters.

PMID- 30199265
TI  - Biologically Inspired Total Synthesis of Ulbactin F, an Iron-Binding Natural
      Product.
AB  - Natural products from environmental microbiomes provide exquisite templates for
      elucidating biological activity in the search for new drugs. A recently
      discovered marine Brevibacillus sp. metabolite, ulbactin F, was found to inhibit
      tumor cell migration and invasion at IC50 < 3 MUM. Herein, we disclose the first
      total synthesis of ulbactin F and epi-ulbactin F, which was modeled after the
      biosynthetic pathway. The scaffold bears structural similarity to siderophores of
      human pathogens but contains a novel tricyclic ring system derived from cysteine.
      We have found that ulbactin F forms low-affinity metal complexes, with a
      preference for Fe3+ and Cu2+, which may hint both at its environmental role and
      its antimetastatic mechanism of action.

PMID- 30199266
TI  - High Magnetic Field Detunes Vibronic Resonances in Photosynthetic Light
      Harvesting.
AB  - The origin and role of oscillatory features detected in recent femtosecond
      spectroscopy experiments of photosynthetic complexes remain elusive. A key
      hypothesis underneath of these observations relies on electronic-vibrational
      resonance, where vibrational levels of an acceptor chromophore match the donor
      acceptor electronic gap, accelerating the downhill energy transfer. Here we
      identify and detune such vibronic resonances using a high magnetic field that
      exclusively shifts molecular exciton states. We implemented ultrafast pump-probe
      spectroscopy into a specialized 25 T magnetic field facility and studied the
      light-harvesting complex PC645 from a cryptophyte algae where strongly coupled
      chromophores form molecular exciton states. We detected a change in high
      frequency coherent oscillations when the field was engaged. Quantum chemical
      calculations coupled with a vibronic model explain the experiment as a magnetic
      field-induced shift of the exciton states, which in turn affects the electronic
      vibrational resonance between pigments within the protein. Our results
      demonstrate the delicate sensitivity of interpigment coherent oscillations of
      vibronic origin to electronic-vibrational resonance interactions in light
      harvesting complexes.

PMID- 30199267
TI  - BASALT: The Future of Mars, on Earth Today.

PMID- 30199269
TI  - Correlation of Immune Cells and Cytokines in the Tumor Microenvironment with
      Elevated Neutrophil-To-Lymphocyte Ratio in Blood: An Analysis of Muscle-Invasive
      Bladder Cancer.
AB  - We investigated the relationship between Neutrophil-to-lymphocyte ratio (NLR) and
      the quantities of neutrophil elastase, CD3, Foxp3, and CD204 in tumor
      infiltrating cells and circulating cytokines (IL-2, -6, -8, 17a, and TGF-beta) in
      muscle-invasive bladder cancer. IL-6 and IL-8 levels showed a significant
      correlation with NLR in blood and Foxp3+ cells around the tumor. After co-culture
      of peripheral blood cells with bladder cancer cell lines, the induction of
      regulatory T cell (Treg) was higher in T24 whose IL-6 and IL-8 levels were
      higher. High NLR correlates with increased IL-6 and IL-8 and Treg expression.

PMID- 30199271
TI  - Tongue shapes for rhotics in school-age children with and without residual speech
      errors.
AB  - Speakers of North American English use variable tongue shapes for rhotic sounds.
      However, quantifying tongue shapes for rhotics can be challenging, and little is
      known about how tongue shape complexity corresponds to perceptual ratings of
      rhotic accuracy in children with residual speech sound errors (RSE). In this
      study, 16 children aged 9-16 with RSE and 14 children with typical speech (TS)
      development made multiple productions of 'Let Robby cross Church Street'.
      Midsagittal ultrasound images were collected once for children with TS and twice
      for children in the RSE group (once after 7 h of speech therapy, then again after
      another 7 h of therapy). Tongue contours for the rhotics in the four words were
      traced and quantified using a new metric of tongue shape complexity: the number
      of inflections. Rhotics were also scored for accuracy by four listeners. During
      the first assessment, children with RSE had fewer tongue inflections than
      children with TS. Following 7 h of therapy, there were increases in the number of
      inflections for the RSE group, with the cluster items cross and Street reaching
      tongue complexity levels of those with TS. Ratings of rhotic accuracy were
      correlated with the number of inflections. Therefore, the number of inflections
      in the tongue, an index of tongue shape complexity, was associated with perceived
      accuracy of rhotic productions.

PMID- 30199270
TI  - Frailty assessment and impact of frailty on outcomes after transcatheter aortic
      valve replacement.
AB  - INTRODUCTION: Certain frail patients fail to achieve adequate functional or
      mortality benefit despite successful transcatheter aortic valve replacement
      (TAVR). Therefore, frailty assessment methods are becoming an important tool to
      identify and intervene on this high-risk patient subset for improving clinical
      outcomes. Areas covered: The authors provide an overview of frailty and frailty
      assessment tools being used in clinical practice and discuss the impact of
      frailty on the cardiac patients, particularly among the TAVR population. Expert
      commentary: Available evidence suggests that frailty assessment is critical for
      identifying patients at high risk of morbidity and mortality after TAVR
      procedures. However, there is lack of consensus for the best methodology to
      determine frailty and its optimal management in TAVR populations. Although,
      physical exercise is a commonly employed intervention to reduce frailty, a
      greater attention towards improving nutrition may convey more benefit than either
      intervention alone. Ongoing studies are investigating the benefits of a
      multicomponent approach to improve clinical outcomes in frail patients undergoing
      TAVR.

PMID- 30199272
TI  - Primary sclerosing cholangitis in children versus adults: lessons for the clinic.
AB  - INTRODUCTION: Primary sclerosing cholangitis (PSC) is a rare cholestatic disorder
      that presents with multifocal biliary strictures. PSC has a variable course but
      often leads to progressive liver disease, and most patients will eventually
      require liver transplantation. PSC has a strong association with inflammatory
      bowel disease and autoimmune liver disease. Areas covered: The objective of this
      article is to compare and contrast the clinical features and natural history of
      PSC in children to adults. We performed a PubMed search of the English literature
      using keywords 'primary sclerosing cholangitis', 'PSC', 'children', and
      'pediatric.' Expert commentary: While certain features of PSC are similar in the
      pediatric and adult population, there are unique features of pediatric PSC. More
      longitudinal studies are needed to better understand the natural history of
      pediatric PSC. It is conceivable that treatment for PSC that will alter the
      course of disease may become available in the future.

PMID- 30199273
TI  - Factors Affecting Enjoyment of Virtual Reality Games: A Comparison Involving
      Consumer-Grade Virtual Reality Technology.
AB  - OBJECTIVE: This study investigated psychological responses to playing videogames
      using a virtual reality (VR) head-mounted display (HMD). We also investigated how
      cybersickness impacts the sense of presence one feels in the virtual environment,
      as well as how cybersickness affects enjoyment. MATERIALS AND METHODS:
      Participants played randomly assigned VR games that varied in the level of
      sensory conflict they provided: "Lucky's Tale," "Elite: Dangerous," and
      "Minecraft." Results were compared based on two headset conditions-the Oculus DK2
      and the recently released Oculus Rift Consumer Version (CV1). RESULTS:
      Cybersickness was not reduced by playing games with a VR HMD of higher
      technological quality-the Oculus Rift CV1. Furthermore, cybersickness responses
      were significantly different based on the level of sensory conflict in the games.
      Games with less sensory conflict, such as third-person platformer games, or space
      and flight simulator games, produce less cybersickness in players than first
      person games. Enjoyment of VR games was shown to be directly influenced by a
      sense of spatial presence, which was affected by interactivity and realism.
      Findings suggest that the variables that are important to the enjoyment of
      console, mobile, or motion-based games are consistently important to enjoyment of
      VR games. CONCLUSION: Better technology does not affect the frequency or severity
      of cybersickness for players; but sensory conflict has a significant impact on
      how sick users become. Additionally, we present a model that indicates how
      enjoyment is produced in VR gaming experiences. These findings bear further
      investigation as new methods of interacting with VR games are developed.

PMID- 30199274
TI  - The Characterization of Biofilm Formation and Detection of Biofilm-Related Genes
      in Salmonella Isolated from Beef Processing Plants.
AB  - The biofilm formation behavior of Salmonella isolated from beef processing plants
      was investigated under varying temperatures (4 degrees C, 10 degrees C, 25
      degrees C, 37 degrees C, and 42 degrees C) and pH (4.5, 5.0, 5.5, 6.0, 7.0, and
      8.0). The relationships between the presence of biofilm-related genes and the
      biofilm formation capacity were evaluated. A total of 77 Salmonella strains in 8
      different serotypes were assessed: Salmonella Agona (n = 43), Salmonella
      Senftenberg (n = 13), Salmonella Meleagridis (n = 8), Salmonella Derby (n = 7),
      Salmonella Kottbus (n = 2), Salmonella Calabar (n = 2), Salmonella Kingston (n =
      1), and Salmonella Typhimurium (n = 1). The results showed that all tested
      Salmonella strains produced biofilm at 25 degrees C and 37 degrees C after 3 d,
      and Salmonella Kingston and Salmonella Senftenberg had higher biofilm production
      than other strains under test conditions. Serotype, incubation temperature, pH,
      and their interactions had significant effects on biofilm formation for
      Salmonella. The strongest biofilm formation capacity of Salmonella (serovar
      Agona, Senftenberg, Kottbus, Calabar, Kingston, and Typhimurium) occurred at 25
      degrees C and at pH 7.0. Biofilm formation was significantly inhibited for all
      Salmonella strains incubated at 4 degrees C. The detection rates of genes rpoS,
      fliC, wcaA, and invA were 100%, and the rates of genes csgB, csgD, csrA, sirA,
      adrA, gly, fimH, sdiA, ompR, sipB, sipC, luxS, and pfs exceeded 75% among all
      biofilm producer strains. The detection rate of igaA was significantly different
      between different biofilm producers. Based on the findings in this study, useful
      information on biofilm formation of Salmonella isolated from beef processing
      plants in China is provided, which could help clear the technological hurdle in
      delaying biofilm production to deal with risks from Salmonella biofilms in the
      beef industry.

PMID- 30199275
TI  - Role of Digital Games in Self-Management of Cardiovascular Diseases: A Scoping
      Review.
AB  - OBJECTIVE: Examine research on the use of digital games to improve self
      management (SM) behaviors in patients diagnosed with cardiovascular diagnoses of
      hypertension, coronary artery disease, heart failure, or myocardial infarction.
      MATERIALS AND METHODS: For this scoping review, the CINAHL, PubMed, and Web of
      Science databases were searched for studies published from January 1, 2008 to
      December 20, 2017 using terms relevant to digital games and cardiovascular
      diseases (CVDs). RESULTS: Eight articles met the inclusion/exclusion criteria,
      seven of which presented studies with participants 50 years or older. Five of the
      eight studies assessed physical activity. Only two studies included a control
      group. Digital games significantly improved exercise capacity and energy
      expenditure but did not affect quality of life, self-efficacy, anxiety, or
      depression. Digital games were found enjoyable by 79%-93% of participants,
      including those with lower education or age; however, barriers to game use
      included being tired or bored, lack of interest in digital games, poor perception
      of fitness through games, sensor limitations, conflicts with daily life routine,
      and preferences for group exercise. Average adherence ranged from 70% to 100%
      over 2 weeks to 6 months of study duration, with higher adherence rates in
      studies that included human contact through supervision or social support.
      CONCLUSION: Paucity of studies about digital games for CVD SM behaviors precludes
      the need to undertake a full systematic review. Future studies examining digital
      games should include larger sample sizes, longer durations, game-design guided by
      behavioral change theoretical frameworks, and CVD SM behaviors in addition to
      physical activity behaviors.

PMID- 30199276
TI  - Two Days at the Hunter College Symposium on Radiometals in New York City.

PMID- 30199277
TI  - Liberating carotid arteries: measuring arterial pressure through femoral artery
      in mice.
AB  - Researches involving arterial pressure measurements in mice have primarily relied
      on carotid arterial catheterization. However, in some circumstances, measuring
      arterial pressure through the carotid arterial impairs accuracy. This study was
      aimed to evaluate whether femoral artery could displace carotid artery for the
      blood pressure (BP) measurements in mice. Fifty-six Swiss mice (n = 14 in each
      group) were randomized into four groups: control, left femoral artery, right
      femoral artery, and union group, in which BP was measured through left carotid,
      left femoral, right femoral artery, and simultaneously from right femoral artery
      and left carotid artery, respectively. Arterial pressure was recorded for 5 min
      after catheterization. There was no significant difference of the success rate
      and mortality rate among four groups (P > 0.05), and no obvious difference (P >
      0.05) of catheterization time among the first three groups. For intergroup
      comparison of arterial pressure, there was no significant difference (P > 0.05)
      of the systolic blood pressure (SBP), diastolic BP, mean arterial pressure, and
      pulse pressure among the first three groups. For intragroup comparison, SBP,
      diastolic blood pressure (DBP), mean arterial pressure (MAP) monitored from right
      femoral artery were similar (P > 0.05) with those from left carotid artery, with
      significantly positive correlation. The mean values of difference of SBP, DBP,
      and MAP were -1.3, 1.2, and 0.5 mmHg, respectively. Our results indicated that
      femoral artery catheterization could be a safe, feasible, reliable, and accuracy
      alternative for the direct measurement of arterial pressure in anesthesia mice.

PMID- 30199278
TI  - A Hot Health Policy Summer.
AB  - Last summer the administration finalized new rules on short-term plans and
      approved new state waivers. Litigation continues over the individual mandate,
      risk adjustment, and ACA "sabotage."

PMID- 30199279
TI  - The pharmacological interactions between direct-acting antivirals for the
      treatment of chronic hepatitis c and psychotropic drugs.
AB  - INTRODUCTION: Most direct-acting antivirals (DAAs) and psychotropic drugs are
      metabolized by or induct/inhibit CYP enzymes and drug transporters. Although they
      are frequently coadministered, the drug-drug interactions (DDIs) have been little
      studied. Therefore, the aim of this review is to describe the interactions
      between the approved DAA or combination regimens and the main psychoactive
      substances, including legal and illegal drugs of abuse. Areas covered: We
      performed a literature search on PubMed database on drug interactions with the
      currently available antivirals for hepatitis C and a review of the information on
      pharmacokinetics, metabolism, and drug interactions from www.hep
      druginteractions.org and from all the Summary of Product Characteristics (SmPC).
      This review covers the DDI between the DAA regimens approved, such as simeprevir
      and sofosbuvir, paritaprevir, glecaprevir, voxilaprevir, ombitasvir, ledipasvir,
      daclatasvir and sofosbuvir, elbasvir and grazoprevir, sofosbuvir and velpatasvir,
      glecaprevir/pibrentasvir, sofosbuvir and velpatasvir, and main psychotropic
      agents. Expert Commentary: DAA regimens based on sofosbuvir combination usually
      have less DDI than protease inhibitor-based regimens. Among protease inhibitors
      regimens, new combinations, such as glecaprevir/elbasvir and
      grazoprevir/elbasvir, seemed to have less DDI than the combination POrD
      (paritaprevir/ombitasvir/ritonavir/dasabuvir). However, the analysis of each
      interaction is theoretical and further interaction studies would be necessary to
      confirm actual effect.

PMID- 30199280
TI  - Comorbid morphological disorder apparent in some children aged 4-5 years with
      childhood apraxia of speech: findings from standardised testing.
AB  - There is continuing debate about the origins of productive morphological errors
      in children with speech sound disorders. This is the case for children with
      theorised phonetic and motor disorders, such as children with childhood apraxia
      of speech (CAS, e.g., Ekelman & Aram, 1983; McNeill & Gillon, 2013 ). The
      morphological skills of children with CAS remain relatively unexplored in pre
      schoolers. We investigated English morphology in a retrospective, cross-sectional
      design of 26 children aged 4-5 years who completed the Clinical Evaluation of
      Language Fundamentals-Preschool (2nd edition; Wiig, Secord & Semel, 2006). The
      research aims were to determine: (1) the language profile of the children, (2)
      the accuracy of each morpheme type produced, and (3) how many of those
      morphological errors are explained by speech errors (clusters, late developing
      phonemes, central vowels or weak syllable stress)? The results indicate the group
      of children with CAS had poorer expressive language skills than receptive skills
      and 48% demonstrated difficulties with morphology in word structure and recalling
      sentences subtests. The children had poor accuracy and inconsistent production of
      a range of morphemes and despite many errors due to the speech characteristics of
      the stimuli on the CELF-P2, motor speech concerns could not explain all the
      child's morphological errors. The results suggest morphological difficulties are
      co-morbid to CAS and when this occurs, treatment for morphosyntax is indicated.
      There are also significant clinical implications in the assessment of
      morphosyntax for children with CAS which are discussed.

PMID- 30199281
TI  - Low Gonadotropin Dosage Reduces Aneuploidy in Human Preimplantation Embryos:
      First Clinical Study in a UAE Population.
AB  - TYPE OF STUDY: Retrospective analysis of embryo aneuploidy in patients undergoing
      in vitro fertilization (IVF) cycles. AIM: To evaluate factors that might affect
      the incidence of embryo aneuploidy during IVF cycles. METHODS: Three hundred
      twelve IVF cases were included in the present study. Preimplantation genetic
      testing for aneuploidy (PGT-A) was performed for all the subjects involved.
      Subject stratification was done based on maternal age, gonadotropin drug dosage,
      and IVF outcomes data. Maternal age <35 years were placed in the "Young" age
      group and age >=35 years were placed in the "Advanced Maternal Age" group.
      Similarly, IVF drug administered <200 International units (IU) was considered
      "low dosage," group and >=200 IU were considered "high dosage" group. Patients
      were stratified into four groups-group 1: age <35 years and administered <200 IU;
      group 2: age <35 years and administered >=200 IU; group 3: age >=35 years and
      administered at <200 IU; and group 4: age >=35 years and administered >=200 IU.
      PGT-A results were attained using a next-generation sequencing-based protocol.
      Embryo transfer was guided by transabdominal ultrasound. Statistical significance
      was calculated with the use of chi-square test. RESULTS: One thousand fifty
      blastocyst trophectoderm biopsies from 312 IVF cases were retrieved. The IVF
      outcome of a total of 105 normal cases resulted in 65.71% pregnancies.
      Stratifying for maternal age and IVF drug stimulation with PGT-A analyses we
      found the euploid embryo percentages equal to 37.59% in Group 1; 16.18% in Group
      2; 22.44% in Group 3; and 2.59% in Group 4. Similarly the aneuploid embryo
      (percentage)s were 62.40% for Group 1; 83.81% for Group 2; 77.55% for Group 3;
      and 87.40% for Group 4. CONCLUSION: This is the first clinical study reporting
      that gonadotropin dosage may act as a contributing factor in increasing
      aneuploidy incidences for the patients undergoing IVF cycles in the UAE
      population. This study shows that in all patient age groups, lower drug
      stimulation leads to an increasing trend in embryo euploidy.

PMID- 30199282
TI  - Myopathic mutations in the beta-chain of tropomyosin differently affect the
      structural and functional properties of betabeta- and alphabeta-dimers.
AB  - Tropomyosin (Tpm) is an actin-binding protein that plays a vital role in the
      regulation of muscle contraction. Fast skeletal muscles express 2 Tpm isoforms,
      alpha (Tpm 1.1) and beta (Tpm 2.2), resulting in the existence of 2 forms of
      dimeric Tpm molecule: alphaalpha-homodimer and alphabeta-heterodimer. betabeta
      Homodimer is unstable and absent in the native state, despite which most of the
      studies of myopathy-relating Tpm mutations have been performed on the betabeta
      homodimer. Here, we applied different methods to investigate the effects of
      myopathic mutations R133W and N202K in the beta-chain of Tpm on properties of
      alphabeta-heterodimers and to compare them with the features of betabeta
      homodimers with the same mutations. The results show that properties of alphabeta
      Tpm and betabeta-Tpm with substitutions in the beta-chain differ significantly,
      and this indicates that the effects of myopathic mutations in the Tpm beta-chain
      should be studied on the Tpm alphabeta-heterodimer.-Bershitsky, S. Y., Logvinova,
      D. S., Shchepkin, D. V., Kopylova, G. V., Matyushenko, A. M. Myopathic mutations
      in the beta-chain of tropomyosin differently affect the structural and functional
      properties of betabeta- and alphabeta-dimers.

PMID- 30199283
TI  - Milk osteopontin promotes brain development by up-regulating osteopontin in the
      brain in early life.
AB  - Osteopontin (OPN) is a pleiotropic protein and is abundantly present in milk. Its
      functions include immune modulation and cellular proliferation and
      differentiation. OPN is highly expressed in the brain. We investigated the
      effects of milk-derived OPN on brain development of mouse pups. Wild-type (WT)
      dams producing OPN+ milk and OPN knockout (KO) dams producing OPN- milk nursed WT
      pups (OPN+/+), yielding 2 pup treatment groups, OPN+ OPN+/+ and OPN- OPN+/+, for
      comparison. Preliminary studies supported use of this model by showing high
      concentrations of OPN in milk of WT dams and no OPN in milk of OPN KO dams, and
      production of similar amounts of milk by WT and KO dams. The ability of ingested
      milk OPN to enter the brain was revealed by appearance of orally gavaged [125I]
      labeled and antibody-probed milk OPN in brains of pups. Brain OPN mRNA levels
      were similar in both nursed groups, but the brain OPN protein level was
      significantly lower in the OPN- OPN+/+ group at postnatal days 6 and 8. Behavior
      tests showed impaired memory and learning ability in OPN- OPN+/+ pups. In
      addition, our study revealed increased expression of myelination-related proteins
      and elevated proliferation and differentiation of NG-2 glia into oligodendrocytes
      in the brain of OPN+ OPN+/+ pups, accompanied by increased activation of ERK-1/2
      and PI3K/Akt signaling. We concluded that milk OPN can play an important role in
      brain development and behavior in infancy by promoting myelination.-Jiang, R.,
      Prell, C., Lonnerdal, B. Milk osteopontin promotes brain development by up
      regulating osteopontin in the brain in early life.

PMID- 30199284
TI  - Thymidylate kinase is critical for DNA repair via ATM-dependent Tip60 complex
      formation.
AB  - Cellular supply of deoxythymidine triphosphate (dTTP) is crucial for DNA
      replication and repair. Thymidylate kinase (TMPK) catalyzes the conversion of
      thymidine monophosphate to thymidine diphosphate, which is an essential step for
      dTTP synthesis. Despite their major cellular localization in cytosol, TMPK and
      ribonucleotide reductase (RNR) are detected at DNA damage sites for local dNDP
      formation. Because deoxyuridine diphosphate is synthesized by RNR, the
      simultaneous recruitment of TMPK and RNR to DNA damage sites is critical for
      preventing deoxyuridine triphosphate-mediated toxic repair. This study
      investigates the mechanism responsible for the recruitment of TMPK to DNA damage
      sites. Our data demonstrate the requirement of ataxia telangiectasia mutated
      (ATM) kinase activity for TMPK recruitment to DNA lesion sites. Moreover, we find
      that TMPK is able to form the complex with histone acetyltransferase Tip60 and
      RNR. Inhibition of ATM kinase reduces the complex formation and TMPK
      phosphorylation. Our analysis further shows the presence of TMPK phosphorylation
      at serine 88, which is an ATM kinase consensus site. A phosphorylation-defective
      mutation at this site suppresses TMPK recruitment to DNA damage sites and the
      complex formation with Tip60. Finally, we provide evidence that this site is
      critical for the function of TMPK in DNA repair but not for catalytic activity.
      Together, these findings suggest that Tip60-ATM signaling has a functional
      contribution to the recruitment of TMPK to DNA damage sites, thereby increasing
      local dTTP synthesis for DNA repair.-Hu, C.-M., Tsao, N., Wang, Y.-T., Chen, Y.
      J., Chang, Z.-F. Thymidylate kinase is critical for DNA repair via ATM-dependent
      Tip60 complex formation.

PMID- 30199285
TI  - Endothelial calpain systems orchestrate myofibroblast differentiation during
      wound healing.
AB  - The transformation of fibroblasts to myofibroblasts plays a major role in
      fibrogenic responses during dermal wound healing. We show a contribution of
      calpain systems (intracellular regulatory protease systems) in vascular
      endothelial cells (ECs) to myofibroblast differentiation in wound sites. Dermal
      wound healing experiments in mice found that calpastatin (an endogenous inhibitor
      of calpains) is enriched in preexisting vessels but not in newly formed
      capillaries. Transgenic overexpression of calpastatin in ECs delayed wound
      healing in mice as well as reducing the keratinocyte layer, extracellular matrix
      deposition, and myofibroblast accumulation in wound sites. EC and leukocyte
      markers, however, remain unchanged. Calpastatin overexpression reduced the
      expression of genes encoding platelet-derived growth factor-B and PDGF receptor
      beta (PDGFR-beta). Topical application of platelet-derived growth factor-BB
      containing ointment to wounds accelerated healing in control mice, but
      calpastatin overexpression prevented this acceleration. In cultured human dermal
      fibroblasts, alpha-smooth muscle actin and PDGFR-beta were up-regulated by
      coculturing with ECs, but this action was inhibited by suppression of EC calpain
      activity. EC-driven transformation of mouse dermal fibroblasts was also
      suppressed by calpastatin overexpression in ECs. These results suggest that
      endothelial calpain systems influence PDGFR-beta signaling in fibroblasts, EC
      driven myofibroblast differentiation, and subsequent fibrogenic responses in
      wounds.-Miyazaki, T., Haraguchi, S., Kim-Kaneyama, J.-R., Miyazaki, A.
      Endothelial calpain systems orchestrate myofibroblast differentiation during
      wound healing.

PMID- 30199287
TI  - Susie Nanney.

PMID- 30199286
TI  - Screen-Time Policies and Practices in Early Care and Education Centers in
      Relationship to Child Physical Activity.
AB  - BACKGROUND: Few preschool children meet physical activity recommendations,
      whereas the majority exceeds screen-time recommendations. The purpose of this
      study was to examine the relationship of screen-time policies and practices with
      children's physical activity and sedentary time in early care and education (ECE)
      centers. METHODS: We conducted a cross-sectional study of 104 children (3.3 +/-
      0.5 years; 50% girls) attending 10 ECE centers in the United States. Physical
      activity was measured by accelerometry. Screen-time practices were measured by
      classroom observation and director report. Mixed linear models were used to
      examine the relationship of screen-time practices with children's total physical
      activity (TPA) and moderate-to-vigorous physical activity (MVPA) and sedentary
      time, adjusting for child's age, sex, and BMI z-score and taking into account the
      clustering of children within each center. Models were repeated to include
      director-reported active play time as a covariate. RESULTS: More
      limited/supervised screen-time (by observation) was related to higher TPA (p =
      0.0003) and lower sedentary time (p = 0.0003). More limited/supervised screen
      time (by director report) was related to higher TPA (p < 0.0001) and MVPA (p =
      0.021) and lower sedentary time (p < 0.0001). Associations remained significant
      when active play time was included as a covariate. TPA was inversely related to
      computer access (p = 0.0015) and positively related to the use of educational
      screen-time compared with noneducational screen-time (p = 0.04). CONCLUSIONS:
      Limiting computer usage and ensuring screen-time is educational, and integrated
      within the curriculum may benefit children's physical activity levels and reduce
      time spent sedentary.

PMID- 30199289
TI  - Implementation Strategies Used by States to Support Physical Activity Licensing
      Standards for Toddlers in Early Care and Education Settings: An Exploratory
      Qualitative Study.
AB  - BACKGROUND: Child care settings have been a target for childhood obesity
      prevention efforts; changing licensing standards to require physical activity
      (PA)-related best practices is one strategy being used by states. The mechanisms
      used to support implementation by providers remain understudied, despite the
      potential for these efforts to significantly impact child-level outcomes. This
      qualitative study explored the mechanisms used and any outstanding challenges to
      implementation experienced by US states with one specific best practice PA
      licensing standard for toddlers (60-90 min of PA/day). METHODS: All states with
      the selected PA licensing standard were invited to participate (N = 9).
      Interviews were conducted with the licensing administrator and others in the
      state involved with implementation and referred by the Administrator (e.g.,
      Licensing Inspectors). A total of 20 individuals from seven states were
      interviewed. All interviews were recorded, professionally transcribed, and
      analyzed to identify themes. RESULTS: A range of strategies was reported, however
      the majority of interviewees reported that providers experienced few challenges
      with implementation. Steps taken during the rulemaking process and technical
      assistance provided by licensing staff, government and nonprofit partners were
      frequently mentioned as contributing to implementation success. Challenges faced
      by licensing staff included lack of resources and a need for specific, age
      appropriate PA-promoting activities that providers could easily implement.
      CONCLUSIONS: Based on the experience of participating states, other jurisdictions
      may want to explore adding PA-related requirements to their licensing standards.
      The lessons learned from these seven states may be helpful during the rulemaking
      and implementation processes.

PMID- 30199288
TI  - Compliance with the New 2017 Child and Adult Care Food Program Standards for
      Infants and Children before Implementation.
AB  - BACKGROUND: Nationally, child care providers serve nutritious food to over 4.5
      million children each day as part of the federal Child and Adult Care Food
      Program (CACFP). As implementation of the first major revisions to the CACFP
      standards occurs in 2017, understanding how to support compliance is critical.
      METHODS: In 2016, surveys were sent to a randomly selected sample of 2400
      licensed California child care centers and homes. Compliance with the new CACFP
      standards and best practices for infants under 1 year and children 1-5 years of
      age was assessed. Also, compliance was compared by CACFP participation, and
      between centers and homes. Interviews were conducted with 16 CACFP stakeholders
      to further understand barriers to and facilitators of compliance. RESULTS:
      Analysis of 680 survey responses revealed that compliance with most individual
      CACFP standards and best practices examined was high (>60% of sites). However,
      compliance with all new standards was low (<23% of sites). Compliance was lowest
      for timing of introduction of solids to infants, not serving sweet grains,
      serving yogurt low in sugar, and serving appropriate milk types to children. When
      different, compliance was higher for sites participating in CACFP versus
      nonparticipants, and for centers versus homes. Although providers indicated few
      barriers, stakeholders identified the need for incremental and easily accessible
      trainings that provide practical tips on implementation. CONCLUSION: Training on
      a number of topics is needed to achieve full implementation of the new CACFP
      standards to ensure that young children in child care have access to healthier
      meals and snacks.

PMID- 30199290
TI  - Early Childhood Education Centers' Reported Readiness to Implement the Updated
      Child and Adult Care Food Program Meal Pattern Standards in the United States,
      2017.
AB  - BACKGROUND: The Child and Adult Care Food Program (CACFP) serves nutritious
      meals/snacks to >3.6 million children in early childhood education (ECE) centers.
      This study provides a nationwide assessment of nonhome-based CACFP-participating
      ECE centers' awareness of and reported readiness for implementing updated CACFP
      standards/best practices that took effect October 1, 2017. METHODS: A national
      frame of 38,760 centers serving children ages 0-5 was developed. A web-based
      survey of 5483 sampled centers, stratified by census division, was conducted
      between August 22 and September 30, 2017. One thousand three hundred forty-three
      centers (25%) located in 47 states and the District of Columbia responded.
      Surveys were primarily completed by center directors/assistant directors (71%).
      Nonresponse adjusted multivariate regressions were conducted, controlling for
      center/zip code-level characteristics. RESULTS: The majority of centers reported
      being "very" familiar with the updated standards and met specific standards/best
      practices. Centers that reported being "somewhat" (vs. "very") familiar with the
      standards were less prepared and likely to have begun implementation and more
      likely to need additional time, money, and staff. Centers that reported being
      "not"/"somewhat" familiar (vs. "very") with the updated standards were also less
      likely to meet specific standards/best practices. Center preparedness and
      standards/best practices varied by weekly rates/fees charged. Centers in the West
      (vs. South) were more likely to report meeting sugary cereal standards and fruits
      and vegetables as a snack component best practice. CONCLUSIONS: While most
      centers reported familiarity with and were prepared to implement the updated
      CACFP standards, readiness is not universal. Technical assistance and training
      should ensure that all centers are trained on the updated standards.

PMID- 30199292
TI  - Barriers and Facilitators to Compliance with a State Healthy Eating Policy in
      Early Care and Education Centers.
AB  - BACKGROUND: Early care and education (ECE) policies can improve childhood obesity
      risk factors. We evaluated barriers and facilitators to implementing mandatory
      nutrition standards for foods provided in South Carolina ECE centers serving low
      income children, comparing centers participating in the Child and Adult Care Food
      Program (CACFP) with non-CACFP centers. METHODS: We mailed 261 surveys
      (demographics, policies and practices, barriers and facilitators) to center
      directors after new state nutrition standards were implemented in South Carolina.
      We conducted univariate and bivariate analyses to explore relationships between
      barriers, facilitators, and center-level characteristics, by CACFP status.
      RESULTS: We received 163 surveys (62% response rate). Centers had a median
      [interquartile range (IQR)] of 5 (4-7) classrooms and 59 (37.5-89) total children
      enrolled. More than half (60.1%) of directors reported they were moderately or
      fully informed about the standards. The most common barriers were food costs
      (17.8%) and children's food preferences (17.8%). More non-CACFP directors
      reported food costs as a barrier (28.6% vs. 6.5%, p < 0.001), having to spend
      additional money on healthier foods (48.8% vs. 28.6%, p = 0.01), and having to
      provide additional nutrition education to parents (28.6% vs. 11.7%, p = 0.01),
      compared with CACFP directors. CONCLUSIONS: Center directors were generally well
      informed about the nutrition standards. The most common barriers to implementing
      the standards were food costs and children's food preferences. Centers
      participating in CACFP may be in a better position to adhere to new state
      nutrition standards, as they receive some federal reimbursement for serving
      healthy foods and may be more accustomed to regulation.

PMID- 30199293
TI  - Food Purchasing and Preparation at Child Day Care Centers Participating in the
      Child and Adult Care Food Program in the United States, 2017.
AB  - BACKGROUND: More than 3.6 million children are served daily by the Child and
      Adult Care Food Program (CACFP)-participating child day care centers. This study
      provides a nationwide assessment of center-level responsibilities for menu,
      meal/snack preparation, meal preparer training, and food and beverage (F&B)
      purchasing. METHODS: A nationally representative survey of 5483 CACFP child day
      care centers was conducted between August 22, 2017, and September 30, 2017. One
      thousand three hundred forty-three centers (25% response) in 47 states and the
      District of Columbia responded. Descriptive statistics describe center-level
      menu, meal, and purchasing practices and center characteristics. Multivariate
      logistic regressions examined characteristics associated with F&B purchasing
      sources. RESULTS: Menus were primarily prepared by directors/assistant directors
      and on-site food manager/cooks, while site staff primarily prepared meals/snacks.
      Fifty-two percent of meal preparers held a food sanitation license, but only 5%
      had formal nutrition training (e.g., Registered Dietician). Most centers
      purchased F&B from food service providers (63%), local grocery stores (59%),
      warehouse stores (40%), or from 2+ sources (50%). Independent centers were more
      likely to purchase F&B from local grocery stores or 2+, while free or state
      subsidized sites were more likely to purchase from a food service provider and
      less likely to purchase from other sources than were centers charging between
      $101 and $201.99 per week. Centers where an on-site cook/food manager prepared
      the menus were significantly more likely to purchase their F&B from local grocery
      and/or warehouse stores and/or from 2+ sources. CONCLUSIONS: Opportunities exist
      to target CACFP training to specific roles within and specific types of CACFP
      participating child day care centers to facilitate compliance with the updated
      CACFP standards.

PMID- 30199291
TI  - Examining Nutrition and Physical Activity Policies and Practices in Maryland's
      Child Care Centers.
AB  - BACKGROUND: Child care settings provide opportunities for obesity prevention by
      implementing nutrition/physical activity best practices. This study examines how
      center policies, provider training, family education, and center demographics
      relate to best practices for nutrition/physical activity in Maryland's child care
      centers. METHODS: A survey, including minor modifications to The Nutrition and
      Physical Activity Self-Assessment for Child Care (Go NAP SACC), was sent by e
      mail to center directors statewide. Best practice sum scores (dependent variable)
      were calculated, including physical activity (17 items), feeding environment (18
      items), and food served (19 items). Adjusted regression models analyzed the
      number of nutrition/physical activity policies, provider training topics, and
      family education opportunities related to best practice scores. RESULTS: Response
      rate was 40% (n = 610/1506) with 69% independent centers (vs. organization
      sponsored), 19% with Child and Adult Care Food Program (CACFP enrolled), and
      50.2% centers with majority (>=70%) Caucasian children and 16.8% centers with
      majority African American children. Centers reported 40.8% of physical activity
      best practices, 52.0% of feeding environment best practices, and 51.6% of food
      served best practices. Centers reported (mean) 7.9 of 16 nutrition/physical
      activity-relevant policies, 6.9 of 13 provider training topics, and 4.4 of 8
      family education opportunities. Regression models yielded associations with best
      practices: policies and provider training with feeding environment (B = 0.26, p <
      0.001; B = 0.26, p = 0.001, respectively); policies with foods served (B = 0.22,
      p = 0.002); and policies, provider training, and feeding environment with
      physical activity (B = 0.19, p = 0.001; B = 0.24, p = 0.010; B = 0.38, p <
      0.001). CONCLUSIONS: Nutrition/physical activity best practices in child care are
      supported by specific policies, provider training, and family education
      activities.

PMID- 30199294
TI  - Feasibility of a Multicomponent Program to Promote Physical Activity and
      Nutrition in Georgia Low-Income Early Care and Education Settings.
AB  - BACKGROUND: This article describes the process and intermediate outcomes from a
      program implemented in 65 Early Care and Education (ECE) centers serving low
      income families throughout Georgia during the 2014-2017 school years. METHODS:
      The HealthMPowers' Empowering Healthy Choices in Schools, Homes, and Communities
      ECE program was based on the organization's previously successful elementary
      school program and aligns with current early childhood nutrition and physical
      activity recommendations. Participating centers worked with HealthMPowers for up
      to 3 years. A team from each center led changes by conducting annual self
      assessments, creating and implementing improvement plans, and implementing
      nutrition and physical activity programs using educational resources and
      environmental cues. A monitoring and evaluation plan provided ongoing feedback to
      HealthMPowers and centers. Family and staff surveys provided insights into
      behaviors of children, families, and staff. Process measures included specific
      benchmarks (e.g., center leadership team formation, improvement plan
      implementation). Annual self-assessment results served as intermediate outcome
      measures. RESULTS: As of 2017, 65 centers had enrolled in the program. All
      centers formed a health team and completed the baseline self-assessment and most
      implemented an improvement plan (88%). At the 1-year follow-up self-assessment,
      centers reported improvements from baseline including never offering food
      incentives for good behavior (75%-86%), conducting taste testing at least once a
      month (61%-79%), and rarely/never serving sugar-sweetened beverages (93%-96%).
      CONCLUSIONS: Initial process measures from a multicomponent health promotion
      program in ECE were promising. An integrated continuous improvement approach to
      working with child care settings is feasible and likely effective.

PMID- 30199295
TI  - Role of Policies and Practices within Early Care and Education Programs to
      Support Healthy Food and Physical Activity Practices.

PMID- 30199296
TI  - Center-Reported Adherence to Nutrition Standards of the Child and Adult Care Food
      Program.
AB  - BACKGROUND: The Child and Adult Care Food Program (CACFP) sets nutrition
      standards for foods served in participating settings. Licensing regulations in
      many states, including Connecticut (CT), extend these rules to nonparticipating
      facilities. This study evaluates the food environment for preschool-age children
      in CT child care centers and describes center-reported adherence to the CACFP
      nutrition regulations. METHODS: We surveyed directors of licensed CACFP
      participating and non-CACFP centers that served meals and/or snacks. Food served,
      caregiver feeding behavior, nutrition practices and policies, and CACFP knowledge
      were reported by 256 non-CACFP and 87 CACFP centers. We conducted bivariate
      analyses to describe adherence to the CACFP regulations as reported by CACFP and
      nonparticipating centers. Data were collected in 2015-2016 and analyzed in 2017.
      RESULTS: CACFP centers reported more engagement in recommended feeding and
      nutrition practices than non-CACFP centers, including serving more fresh fruit
      and whole grains at snack time, serving low-fat milk for meals/snacks, and use of
      family style dining and positive caregiver behaviors. No center reported serving
      soda, only a few had fruit drinks, and the majority prohibited parents from
      sending in sugary drinks. Despite the licensing regulations about compliance with
      the CACFP nutrition standards, 52% of non-CACFP centers had never heard of CACFP
      and only 21% received information about following the CACFP standards and
      practices. CONCLUSIONS: CACFP participation is associated with better center
      reported adherence to the CACFP nutrition standards and feeding practices. Poor
      awareness about CACFP among nonparticipating centers needs to be addressed to
      improve compliance with the CACFP nutrition standards.

PMID- 30199297
TI  - State Regulations Promoting Infant Physical Activity in Early Care and Education.
AB  - BACKGROUND: State policies have the potential to improve early care and education
      (ECE) settings, but little is known about the extent to which states are updating
      their licensing and administrative regulations, especially in response to
      national calls to action. In 2013, we assessed state regulations promoting infant
      physical activity in ECE and compared them with national recommendations. To
      assess change over time, we conducted this review again in 2018. METHODS: We
      reviewed regulations for all US states for child care centers (centers) and
      family child care homes (homes) and compared them with three national
      recommendations: (1) provide daily tummy time; (2) use cribs, car seats, and high
      chairs for their primary purpose; and (3) limit the use of restrictive equipment
      (e.g., strollers). We performed exact McNemar's tests to compare the number of
      states meeting recommendations from 2013 to 2018 to evaluate whether states had
      made changes over this period. RESULTS: From 2013 to 2018, we observed
      significant improvement in one recommendation for homes-to use cribs, car seats,
      and high chairs for their primary purpose (odds ratio 11.0; 95% CI 1.6-47.3; p =
      0.006). We did not observe any other significant difference between 2013 and 2018
      regulations. CONCLUSIONS: Despite increased awareness of the importance of early
      life physical activity, we observed only modest improvement in the number of
      states meeting infant physical activity recommendations over the past 5 years. In
      practice, ECE programs may be promoting infant physical activity, but may not be
      required to do so through state regulations.

PMID- 30199298
TI  - Examining Relationships between Food Procurement Characteristics and Nutritional
      Quality in Washington State Child Care Settings.
AB  - BACKGROUND: Sixty percent of US children 5 years old and under receive up to two
      thirds of their daily nutrition in early care and education (ECE) settings.
      Although participation in the federal Child and Adult Care Food Program (CACFP)
      is shown to improve nutrition, little is known about the relationship between
      procurement practices (where and how child care programs purchase food) and
      nutrition in ECE settings or whether these practices differ depending on
      participation in CACFP. METHODS: We assessed self-reported nutrition practices
      and procurement practices by CACFP participation using a 2013 cross-sectional
      survey of 690 Washington ECE centers ("Centers") and 1260 family homes (family
      home child care [FHCCs]) serving children aged 2-5 years old using validated
      survey tools. We examined the relationship between procurement variables (i.e.,
      main store and main mode) and nutrition scores using multinomial logistic
      regression models that adjusted for sociodemographic and program characteristics.
      RESULTS: In-person shopping was the primary mode of shopping for all programs,
      regardless of CACFP participation. Some Centers but very few FHCCs reported
      online shopping as their primary mode. Centers and non-CACFP FHCCs shopped
      primarily at megastores (Costco, Target, etc.). CACFP FHCCs used both megastores
      and grocery stores (Albertsons, QFC, etc.) at similar rates. Adjusted multinomial
      models found that shopping online or at two or more stores was associated with
      higher nutritional quality of foods served by programs. CONCLUSIONS:
      Understanding the procurement behaviors of ECE programs helps to illuminate and
      prioritize potential interventions that would support healthy food purchases.

PMID- 30199299
TI  - Knowledge, understanding, attitude, perception and views on HPV infection and
      vaccination among health care students and professionals in Malaysia.
AB  - The human papilloma virus (HPV) is known to be a major causative agent of
      cervical cancers and warts, limited study has been conducted on its associated
      factors among health care students and professionals in Malaysia. The present
      study was carried to explore the knowledge, understanding, attitude, perception
      and views about HPV infection and vaccination. A total of 576 respondents were
      recruited to complete a self-administered questionnaire through convenience
      sampling across Malaysia. 80.% and of the females respondents exhibited a
      positive attitude towards knowledge and understanding and 60% exhibited a
      positive towards attitude, perception and views. Almost 65% of the population
      were in agreement that HPV can be transmitted sexually, and 56.7% felt strongly
      that sexually active persons should essentially be vaccinated. The corresponding
      values were somewhat lower among the male respondents. Regression analysis
      suggested that knowledge and understanding were strong associated with gender,
      age, and occupation. Attitude, perception and views were also evidently
      associated with gender and age. The Ministry of Health should take steps to
      improve awareness among the citizens. Efforts should be made to educate people on
      the risk of HPV as a sexually transmitted diseases associated with HPV, and on
      the availability of discounted and safe HPV vaccines in government hospitals to
      increase the uptake rate of HPV vaccines among the Malaysian population.

PMID- 30199301
TI  - Oral corticosteroid exposure and increased risk of related complications in
      patients with noninfectious intermediate, posterior, or panuveitis: Real-world
      data analysis.
AB  - PURPOSE: This study causally examined the dose-response relationship between oral
      corticosteroids (OCS) exposure and long-term complications among noninfectious
      uveitis adult patients in the United States. METHODS: The study design was
      longitudinal, retrospective cohort using Truven Health MarketScan claims database
      years 2000-2015. The index date was the first day after diagnosis on which OCS>=
      5 mg prednisone equivalent was administered. The period following the index date
      was parsed into quarters for tracking OCS-related complications; follow-up time
      was censored when patients switched off of OCS monotherapy. Each quarter of
      follow-up was divided into 4 groups based on the mean cumulative daily OCS dose
      (< 7.5 mg; 7.5 to < 30 mg; 30 to < 60 mg; and >= 60 mg) and covariate balancing
      propensity scoring was used to balance groups on baseline characteristics in the
      first quarter post-index. Marginal structural models (MSMs) were employed to
      account for time-varying endogeneity between temporal changes in mean cumulative
      OCS dose and the risk of complications. Patients with systemic autoimmune
      conditions at baseline were excluded. RESULTS: The study sample included 3966
      patients with a median follow-up of 2 years. Compared to those receiving < 7.5
      mg, patients with higher mean cumulative OCS dose had 10%, 16%, and 28% higher
      risk, respectively, of any OCS-related complication in any given quarter.
      CONCLUSIONS: A moderate dose-response relationship was found between the long
      term use of OCS monotherapy and the risk of developing complications in
      noninfectious intermediate, posterior, or panuveitis patients. Future research
      should examine optimal approaches to achieve inflammation control while
      minimizing OCS exposure.

PMID- 30199300
TI  - Non-neutralizing antibodies increase endogenous circulating Ang1 levels.
AB  - Ang1 is a soluble ligand to receptor Tie2, and increasing the circulating Ang1
      level may improve vascular stabilization under certain disease conditions. Here,
      we found that the circulating Ang1 level was significantly increased in
      cynomolgus monkeys treated with non-neutralizing anti-Ang1 antibodies. Improving
      the antibodies' pharmacokinetic properties by IgG Fc mutations further increased
      the circulating Ang1 level. However, the mutations decreased the thermal
      stability of the molecules, which may limit their use as therapeutic antibodies.
      Nevertheless, we showed that non-neutralizing antibodies may have therapeutic
      potential by increasing the level of a target molecule in the circulation.

PMID- 30199302
TI  - Vaccine-related attitudes and decision-making among uninsured, Latin American
      immigrant mothers of adolescent daughters: a qualitative study.
AB  - Uninsured Latin American immigrant women are at increased risk for vaccine
      preventable diseases, such as cervical cancer; yet gaps in vaccine coverage
      persist. The purpose of this study was to explore vaccine-related knowledge,
      attitudes and decision-making for tetanus, diphtheria, and acellular pertussis
      (Tdap) vaccine, meningococcal conjugate vaccine (MenACWY), and human
      papillomavirus (HPV) vaccine among uninsured Latin American immigrant mothers of
      adolescent daughters. A purposive sample of 30 low-income, uninsured,
      predominantly Latin-American immigrant mothers of adolescent daughters aged 13-17
      were recruited from two academic-community managed health clinics in Virginia.
      From March-September 2016, data were collected through in-person, semi-structured
      interviews, in English or Spanish. For data analysis, conventional content
      analysis was employed. The majority of participants self-identified as Hispanic
      and had less than a high-school level education. Key themes included: general
      acceptance of vaccines; associating vaccines with prevention/protection; minimal
      vaccine hesitancy; and lack of knowledge regarding vaccine-preventable diseases,
      vaccines recommended for adolescents, and adolescent daughters' vaccination
      history. Doctors' recommendation, school requirements, and the media were key
      influencers of vaccination. Mothers were the primary decision-maker regarding
      vaccine uptake among their adolescent daughters. Findings highlight the need for
      efforts to help uninsured Latin American immigrant mothers better understand
      vaccines, and provide linkages to affordable, accessible vaccines among under
      resourced populations.

PMID- 30199304
TI  - Analysis of Efficacy and Toxicity Profile of First-Line Sunitinib or Pazopanib in
      Metastatic Clear Cell Renal Cell Carcinoma in the Brazilian Population.
AB  - Purpose Sunitinib and pazopanib are multitargeted tyrosine kinase inhibitors
      (TKIs) that act against vascular endothelial growth factor receptors and are
      standard first-line treatment options for metastatic clear cell renal cell
      carcinoma (ccRCC). The Brazilian public health system diverges from the
      randomized clinical trials in the availability of first and subsequent lines of
      treatment and in clinical and demographic characteristics of patients. Therefore,
      it is essential to describe the history of advanced ccRCC during and after TKI
      treatment in this population. Methods We performed a retrospective analysis of
      patients with advanced ccRCC treated with a first-line TKI (either sunitinib or
      pazopanib) between February 2009 and March 2017 in a single academic Brazilian
      cancer center (Instituto do Cancer do Estado de Sao Paulo). Results Of the 222
      patients, 109 were treated with sunitinib and 113 with pazopanib. The median
      duration of treatment and overall survival (OS) were 6.4 and 15.2 months for
      sunitinib and 6.7 and 14.2 months for pazopanib, respectively. Discontinuation of
      treatment occurred secondarily to progressive disease or death in 64.2% of
      patients using sunitinib and in 54.8% of patients using pazopanib. Adverse events
      were responsible for discontinuation of treatment in 28.4% of patients in the
      sunitinib group and in 22.1% in the pazopanib group. According to Memorial Sloan
      Kettering Cancer Center risk categories, the OS was 32.9 months, 15.9 months, and
      8.1 months for low risk, intermediate risk, and poor risk, respectively (hazard
      ratio, 1.72; 95% CI, 1.13 to 2.26; P < .001). Conclusion The use of TKI
      inhibitors as first-line treatment of metastatic RCC is effective and feasible in
      the Brazilian public health. However, the median OS of our population is
      considerably lower compared with the prospective trials that evaluated the same
      drugs.

PMID- 30199303
TI  - Site-specific conjugation allows modulation of click reaction stoichiometry for
      pretargeted SPECT imaging.
AB  - Antibody pretargeting is a promising strategy for improving molecular imaging,
      wherein the separation in time of antibody targeting and radiolabeling can lead
      to rapid attainment of high contrast, potentially increased sensitivity, and
      reduced patient radiation exposure. The inverse electron demand Diels-Alder
      'click' reaction between trans-cyclooctene (TCO) conjugated antibodies and
      radiolabeled tetrazines presents an ideal platform for pretargeted imaging due to
      rapid reaction kinetics, bioorthogonality, and potential for optimization of both
      slow and fast clearing components. Herein, we evaluated a series of anti-human
      epidermal growth factor receptor 2 (HER2) pretargeting antibodies containing
      distinct molar ratios of site-specifically incorporated TCO. The effect of
      stoichiometry on tissue distribution was assessed for pretargeting TCO-modified
      antibodies (monitored by 125I) and subsequent accumulation of an 111In-labeled
      tetrazine in a therapeutically relevant HER2+tumor-bearing mouse model. Single
      photon emission computed tomography (SPECT) imaging was also employed to assess
      tumor imaging at various TCO-to-monoclonal antibody (mAb) ratios. Increasing TCO
      to-mAb molar ratios correlated with increased in vivo click reaction efficiency
      evident by increased tumor distribution and systemic exposure of 111In-labeled
      tetrazines. The pharmacokinetics of TCO-modified antibodies did not vary with
      stoichiometry. Pretargeted SPECT imaging of HER2-expressing tumors using 111In
      labeled tetrazine demonstrated robust click reaction with circulating antibody at
      ~2 hours and good tumor delineation for both the 2 and 6 TCO-to-mAb ratio
      variants at 24 hours, consistent with a limited cell-surface pool of pretargeted
      antibody and benefit from further distribution and internalization. To our
      knowledge, this represents the first reported systematic analysis of how
      pretargeted imaging is affected solely by variation in click reaction
      stoichiometry through site-specific conjugation chemistry.

PMID- 30199305
TI  - Patient Factors Associated With Delays in Obtaining Cancer Care in Botswana.
AB  - Purpose Delays in diagnosis and treatment of cancers can lead to poor survival.
      These delays represent a multifaceted problem attributable to patient, provider,
      and systemic factors. We aim to quantify intervals from symptom onset to
      treatment start among patients with cancer in Botswana and to understand
      potential risk factors for delay. Patients and Methods From December 2015 to
      January 2017, we surveyed patients seen in an oncology clinic in Botswana. We
      calculated proportions of patients who experienced delays in appraisal (between
      detecting symptoms and perceiving a reason to discuss them with provider, defined
      as > 1 month), help seeking (between discussing symptoms and first consultation
      with provider, defined as > 1 month), diagnosis (between first consultation and
      receiving a diagnosis, defined as > 3 months), and treatment (between diagnosis
      and starting treatment, defined as > 3 months). Results Among 214 patients with
      cancer who completed the survey, median age at diagnosis was 46 years, and the
      most common cancer was cancer of the cervix (42.2%). Eighty-one percent of
      patients were women, 60.7% were HIV infected, and 56.6% presented with advanced
      cancer (stage III or IV). Twenty-six percent of patients experienced delays in
      appraisal, 35.5% experienced delays help seeking, 63.1% experienced delays in
      diagnosis, and 50.4% experienced delays in treatment. Patient income, education,
      and age were not associated with delays. In univariable analysis, patients living
      with larger families were less likely to experience a help-seeking delay (odds
      ratio [OR], 0.31; P = .03), women and patients with perceived very serious
      symptoms were less likely to experience an appraisal delay (OR, 0.45; P = .032
      and OR, 0.14; P = .02, respectively). Conclusion Nearly all patients surveyed
      experienced a delay in obtaining cancer care. In a setting where care is provided
      without charge, cancer type and male sex were more important predictors of delays
      than socioeconomic factors.

PMID- 30199307
TI  - Predicting behavioral intentions to children vaccination among Chinese parents:
      an extended TPB model.
AB  - Parental behavioral intentions play a key role in children vaccination. The
      present study looks at how parental expectations for the vaccination influence
      their attitudes and behavioral intentions toward children's immunization. The
      theoretical model is developed on TPB model and empirically tested with sample
      data from 380 children aged 0-7 years in mainland China. The structural equation
      modeling and multi-group analysis were used in the model to demonstrate the
      impact of the vaccination services quality, vaccination promotions and public
      opinions on attitudes and vaccination behavioral intention. Results support the
      study's hypotheses and indicate that Vaccination Services Quality (VSQ),
      Vaccination Promotions (VAP) and Public Opinions (PUO) have positive effects on
      Attitudes (ATT) and Vaccination Behavioral Intention (VAI), VSQ has the strongest
      standardized path (.594) while PUO has the least influence (.131), and Attitude
      is complete mediation in all paths. Attitude is key factor that determine the
      parental behavioral intentions, and the internal perception comes from the
      vaccination services quality and the external influence comes from the social
      environment affect the parental attitude. Governments should implement effective
      policies and improve vaccination services quantity to eliminate parental
      misunderstandings.

PMID- 30199306
TI  - Prevalence of BRCA1 and BRCA2 Mutations Among High-Risk Saudi Patients With
      Breast Cancer.
AB  - Purpose Over the past three decades, the incidence rate of breast cancer (BC)
      among Arab women has continually increased. However, data on the prevalence of
      BRCA1/2 mutations are scarce. Although the population in Saudi Arabia is at large
      homogeneous and consanguinity is common, especially in the central, eastern, and
      southern regions of the country, the prevalence of BRCA1 and BRCA2 mutations and
      the characteristics of BC are not well studied in the country. Methods This
      prospective observational study intended to determine the prevalence of BRCA1 and
      BRCA2 mutations and sought to examine the clinicopathologic features of BC
      associated with these mutations. Results Of 310 patients, 270 (87%) had no
      mutation. BRCA mutations were identified in 40 patients; BRCA1 mutations were
      found in 11% of patients, and BRCA2 mutations were found in 2% of patients.
      Variants of unknown significance were found in 15% of patients (45 patients).
      Triple-negative BC (TNBC) accounted for 86% of all patients with BC and
      mutations. The following three recurrent deleterious founder BRCA1 mutations were
      observed: c.4136_4137delCT was observed in five unrelated patients, c.5530delC
      was observed in three unrelated patients, and c.4524G>A mutations were observed
      in five unrelated patients. One novel mutation was identified in the BRCA1 gene
      (c.5512 dup [p.Glu1838Glyfs*42]). Conclusion Among high-risk Saudi patients with
      BC, BRCA1 mutations are prevalent (11%). TNBC is the most common BC subtype.
      Furthermore, age alone does not have a significant association with mutation, but
      a combination of risk factors such as age, familial history, and TNBC has a
      significant association with BRCA mutation.

PMID- 30199308
TI  - Is There Really Increased Cardiovascular Morbidity in Women with Polycystic Ovary
      Syndrome?
AB  - For some time, it has been assumed that women with polycystic ovary syndrome
      (PCOS) are at increased risk of developing cardiovascular disease (CVD). This has
      largely been on the basis of having many risk factors, including abnormal lipid
      profile, insulin resistance, and markers of inflammation. However, despite having
      these and other risk factors, we argue here, in the view of the authors, that
      there is no credible evidence that there is greater CVD morbidity in all women
      with PCOS. We analyze the existing data and discuss that overall CVD risk
      decreases with age when more CVD events are likely to occur, and introduce the
      possibility that there may be some unknown inherent protective factor(s) in women
      with PCOS. It appears that only obesity and/or diabetes mellitus significantly
      increase CVD risk in women with PCOS, and that most of the data showing an
      increased rate of CVD are reported in younger women with PCOS where the absolute
      risk is small. It is also suggested that the CVD risk is predominantly in women
      with the "classic" features of PCOS, including menstrual irregularity and
      hyperandrogenism, particularly in the presence of obesity and diabetes, and
      should not be generalized to all women with PCOS using Rotterdam criteria.
      Strategies for a healthy lifestyle, which should be a lifelong goal for all women
      with PCOS, become particularly important to prevent obesity and diabetes.

PMID- 30199310
TI  - Hepatitis B vaccination among 1997-2011 birth cohorts in rural China: the
      potential for further catch-up vaccination and factors associated with infant
      coverage rates.
AB  - Hepatitis B vaccination rates in China have recently increased. This study aimed
      to investigate infant vaccination coverage for birth cohorts from 1997 to 2011 in
      rural regions and to assess catch-up vaccination potential. We used questionnaire
      based interviews from a cross-section of 6,529 individuals from seven provinces.
      Logistic regression analyses were used to model two measures of infant
      vaccination status, namely, birth dose within 24 hours and three doses within the
      first year of life. During interviews, individuals' vaccination status and
      vaccination plan were recorded. Unvaccinated individuals without plans for future
      vaccination were presented with a hypothetical offer of free vaccination and
      indirect cost compensation. Institutional birth rates were higher than
      vaccination rates, but both increased over time. Vaccination coverage rates were
      not significantly associated with sex. Infant vaccination coverage was positively
      associated with a mother's educational level, household income level, knowledge
      of transmission routes, and perceived duration of protection obtained through
      vaccination. Vaccination status at the time of the survey showed the occurrence
      of catch-up vaccinations, but a notable percentage of individuals remained
      unvaccinated and had no plans for future vaccination. Of these individuals,
      approximately 50% were prepared to accept vaccination if offered free of charge.

PMID- 30199309
TI  - Refractive Changes Associated with Diabetes Mellitus.
AB  - BACKGROUND AND METHODS: Diabetes mellitus is the most prevalent endocrinedisease
      in developed countries. In people with diabetes in addition to visionloss caused
      by diabetic retinopathy transient visual disturbances may occurfrequently caused
      by refractive changes. These changes in refraction are associated with variations
      in blood glucose levelsbut the underlying mechanism is still not fully
      understood. A systematic reviewwith a comprehensive literature search was
      performed in order to clarify the underlyingmechanisms regarding the connection
      of glycaemic control and refractive shift. RESULTS: Some studies have shown that
      increasedblood sugar leads to a myopic shift whilst others demonstrated that this
      changeis in a hyperopic direction. Changes in visual acuity in patients with
      diabetescould be an indicator of inadequate metabolic control or even the first
      sign ofdiabetes mellitus. CONCLUSION: This reviewgives a brief overview of
      current research regarding potential mechanisms ofglycemic control influence on
      refractive error. The aim isto emphasizethe importance ofunderstanding the
      relationship ofblood glucose concentration and refractive changes as one of
      thecommon but overlooked diabetic complications.

PMID- 30199312
TI  - Clinically Localized Prostate Cancer: ASCO Clinical Practice Guideline
      Endorsement of an AUA/ASTRO/SUO Guideline Summary.

PMID- 30199311
TI  - Efficacy and Tolerability of First-Line Cetuximab Plus Leucovorin, Fluorouracil,
      and Oxaliplatin (FOLFOX-4) Versus FOLFOX-4 in Patients With RAS Wild-Type
      Metastatic Colorectal Cancer: The Open-Label, Randomized, Phase III TAILOR Trial.
AB  - Purpose Cetuximab in combination with chemotherapy is a standard-of-care first
      line treatment regimen for patients with RAS wild-type (wt) metastatic colorectal
      cancer (mCRC); however, the efficacy of cetuximab plus leucovorin, fluorouracil,
      and oxaliplatin (FOLFOX) has never before been proven in a controlled and
      randomized phase III trial. To our knowledge, the TAILOR trial (
      ClinicalTrials.gov identifier: NCT01228734) is the first randomized, multicenter,
      phase III study of the addition of cetuximab to first-line FOLFOX prospectively
      choosing a RAS wt population and thus providing confirmative data for the
      efficacy and safety of cetuximab plus FOLFOX versus FOLFOX alone. Patients and
      Methods TAILOR is an open-label, randomized (1:1), multicenter, phase III trial
      in patients from China comparing FOLFOX-4 with or without cetuximab in RAS wt (
      KRAS/ NRAS, exons 2 to 4) mCRC. The primary end point of TAILOR was progression
      free survival time; secondary end points included overall survival time, overall
      response rate, and safety and tolerability. Results In the modified intent-to
      treat population of 393 patients with RAS wt mCRC, adding cetuximab to FOLFOX-4
      significantly improved the primary end point of progression-free survival time
      compared with FOLFOX-4 alone (hazard ratio, 0.69; 95% CI, 0.54 to 0.89; P = .004;
      median, 9.2 v 7.4 months, respectively), as well as the secondary end points of
      overall survival time (current assessment after 300 events: hazard ratio, 0.76;
      95% CI, 0.61 to 0.96; P = .02; median, 20.7 v 17.8 months, respectively) and
      overall response rate (odds ratio, 2.41; 95% CI, 1.61 to 3.61; P < .001; 61.1% v
      39.5%, respectively). Treatment was well tolerated, and there were no new or
      unexpected safety findings. Conclusion The TAILOR study met all of its objectives
      and relevant clinical end points, confirming cetuximab in combination with FOLFOX
      as an effective standard-of-care first-line treatment regimen for patients with
      RAS wt mCRC.

PMID- 30199313
TI  - Effect of Nebulizer Location and Spontaneous Breathing on Aerosol Delivery During
      Airway Pressure Release Ventilation in Bench Testing.
AB  - BACKGROUND: Airway pressure release ventilation (APRV) maintains a sustained
      airway pressure over a large proportion of the respiratory cycle, and has a long
      inspiratory time at high pressure. The purpose of this study was to determine the
      influence of the APRV with and without spontaneous breathing on albuterol aerosol
      delivery with a continuous vibrating-mesh nebulizer (VMN) placed at different
      positions on an adult lung model of invasive mechanical ventilation. METHODS: An
      adult lung model was assembled by connecting a ventilator with a dual-limb
      circuit to an 8-mm inner diameter endotracheal tube (ETT) and collecting filter
      attached to a test lung with set compliance of 0.1 L/cmH2O and resistance of 0.5
      cmH2O/(L.s). Four ventilator modes were compared: pressure control ventilation
      (PCV) with no bias flow, PCV with bias flow of 6 L/min (PCVBF6), APRV with no
      spontaneous breaths (APRV), and APRV with spontaneous breath trigger (APRVs).
      Peak inspiratory pressure, peak end-expiratory pressure, aerosol dose, and
      nebulization time were similar for all modes. The VMN was placed (1) between Y
      piece and inspiratory limb, (2) at the gas outlet of a heated humidifier, and (3)
      at the gas inlet of a heated humidifier. Albuterol sulfate (5 mg/2.5 mL) was
      administered with each run and collected on a filter distal to the ETT. Deposited
      drug was eluted from each filter (purified water) and analyzed by UV
      spectrophotometry at 276 nm. Analysis of variance [general linear model (GLM)
      multivariate] was performed using the linear model of multiple variables,
      significance at p < 0.05. RESULTS: Albuterol (in micrograms, mean +/- standard
      deviation) delivered was higher with VMN placed at the gas inlet of the
      humidifier with each mode of ventilation (p < 0.01). APRVs has the highest
      albuterol delivery followed by PCV, PCVBF6, and APRV (1706.2 +/- 60.9 MUg vs.
      1490.6 +/- 61.1 MUg vs. 1182.3 +/- 61.4 MUg vs. 1153.1 +/- 99.7 MUg,
      respectively, p < 0.001). The minute volume was positively correlated with the
      inhaled albuterol dose. CONCLUSIONS: Spontaneous breathing increased the
      albuterol delivery during APRV, compared with APRV alone and PCV modes. Placing
      the nebulizer proximal to the ventilator was more efficient for all modes tested.

PMID- 30199314
TI  - Spousal Concordance for Objectively Measured Sedentary Behavior and Physical
      Activity Among Middle-Aged and Older Couples.
AB  - PURPOSE: Although it has been proposed that 1 spouse's health behaviors might
      correlate with the other spouse's health behavior among married couples, few
      studies have focused on sedentary behavior. This study examined whether
      objectively measured sedentary behavior and physical activity are correlated with
      each other and whether attachment to one's spouse moderates such correlations
      among middle-aged and older married couples. METHODS: Seventy-two couples
      participated in the survey. This study measured time engaged in sedentary
      behavior and moderate-to-vigorous physical activity (MVPA), step counts by an
      accelerometer for 7 days, and attachment to one's spouse, age, education, and
      frailty by questionnaires. RESULTS: Multiple regression analyses showed that the
      sedentary behaviors of 1 spouse statistically significantly regressed on those of
      the other spouse (beta = .30-.47). The regressions of husbands' MVPA and step
      counts on those of their wives were statistically marginally significant (beta =
      .22-.25), while the regressions of wives' MVPA and step counts on those of their
      husbands were not statistically significant (beta = .15-.18). The interaction
      terms of the attachment with one's spousal accelerometer variables on those of
      the other spouse were not statistically significant (beta = -.02 to .16).
      CONCLUSIONS: This study revealed that sedentary behaviors were correlated with
      each other among couples and attachment to one's spouse did not moderate these
      correlations. Sedentary behaviors of 1 spouse might influence the other,
      regardless of attachment to one's spouse. The concordance for physical activity
      was weaker than that for sedentary behavior.

PMID- 30199315
TI  - Intranasal Filtration of Inhaled Aerosol in Human Subjects as a Function of Nasal
      Pressure Drop.
AB  - BACKGROUND: Intersubject variability in nasal deposition of inhaled aerosol is
      significant because of the differences in nasal anatomy and breathing rate. The
      notable limitation of the majority of previously developed predictive
      correlations is including a limited number of subjects. A few recent studies have
      considered a wide age range of subjects, but the resulting correlations require
      the knowledge of the dimensions of the nasal airways and the properties of
      inhaled gas. In this study empirical correlations are proposed to predict aerosol
      deposition in nasal airways of subjects of different age as a function of
      intranasal pressure drop and the particle aerodynamic diameter. METHODS: The
      experimental nasal deposition and pressure drop data in anatomically correct
      nasal replicas of 5 adults, 13 children aged 4-14 years, and 11 infants aged 3-18
      months were reanalyzed. The range of aerodynamic diameter was 0.5-5.3 MUm and
      physiological breathing at different activity levels was considered. Correlations
      between nasal deposition and a deposition parameter including the aerodynamic
      size of inhaled aerosol and nasal pressure drop were developed with nonlinear
      least-square algorithms. The general coefficient of determination r2 was used to
      evaluate the fitting accuracy for each correlation. RESULTS: New correlations
      were developed to predict the intranasal deposition of particles as a function of
      intranasal pressure drop and particle size for pediatric and adult subjects. The
      intranasal deposition fraction in adults and children can be calculated using the
      same correlation, whereas the intranasal deposition in infants followed a
      different trend line because of higher intranasal pressure drop in infants.
      CONCLUSION: This study was the first offering correlations to predict intranasal
      deposition in multiple age groups using only the aerodynamic size of inhaled
      aerosol and nasal pressure drop. These correlations include the effects of
      intersubject variability in nasal deposition within each age group and among
      different age groups.

PMID- 30199316
TI  - The effect of adaptation of Lactobacillus amylovorus to increasing concentrations
      of sweet potato starch on the production of lactic acid for its potential use in
      the treatment of cannery waste.
AB  - Lactobacillus amylovorus, an amylolytic species, was cultured in increasing
      concentrations of sweet potato starch to test the effect of this progressive
      acclimation on lactic acid production. This research is part of a project on the
      use of the waste stream from a sweet potato cannery to produce lactic acid. The
      media used for this acclimation was a modified version of the de Man, Rogosa and
      Sharpe medium, in which glucose was partially or totally substituted with sweet
      potato starch. The process was done in five steps, starting with 100% glucose in
      the first step and ending with 100% sweet potato starch in the last one. At each
      step, the effectiveness of the acclimation was tested by running fermentations
      with and without pH control for 62 h. The effect of the overall adaptation
      process was tested by comparing the growth and activity of the acclimated vs non
      acclimated bacteria using sweet potato starch as the only source of
      carbohydrates. Growth and activity assessments indicated that L. amylovorus was
      able to ferment sweet potato starch into lactic acid. In most cases, pH control
      resulted in better substrate utilisation and larger amounts of lactic acid. In
      the comparison study, however, the adaptation process had a major influence on
      lactic acid production than the effect of pH. For 20 g L-1 sweet potato starch
      media, adapted L. amylovorus under no pH control yielded 11.20 g L-1 versus the
      non-adapted bacteria, which yielded 7.10 g L-1. Under controlled pH conditions,
      14.80 and 4.20 g L-1 lactic acid were produced by adapted and non-adapted
      bacteria respectively.

PMID- 30199317
TI  - Identification and comprehensive evaluation of a novel biocontrol agent Bacillus
      atrophaeus JZB120050.
AB  - Bacillus spp. have long been used as biocontrol agents because of their efficient
      broad-spectrum antimicrobial activity. We identified a novel strain of Bacillus
      atrophaeus, named JZB120050, from soil. B. atrophaeus JZB120050 had a strong
      inhibitory effect against Botrytis cinerea and many other phytopathogens. Gas
      chromatography-mass spectrometry showed that B. atrophaeus JZB120050 produced
      many secondary metabolites, such as alkanes, alkenes and acids; some of which
      were related to pathogen inhibition. Enzyme activity analysis showed that B.
      atrophaeus JZB120050 secreted cell-wall-degrading enzymes, including chitinase,
      glucanase and protease, which degraded fungal cell walls. Both the novel
      glucanase gene bglu and chitinase gene chit1 were cloned and heterologously
      expressed in Escherichia coli and the products showed strong enzyme activity. In
      addition, B. atrophaeus JZB120050 secreted siderophores and formed a significant
      biofilm. Future studies should focus on these antimicrobial factors to facilitate
      widespread application in the field of agricultural biocontrol.

PMID- 30199318
TI  - A model to predict and optimize machine guarding operator compliance activities
      in a bottling process plant: a developing country experience.
AB  - INTRODUCTION: The accurate tracking, elimination and control of hazards are
      fundamentals in accident avoidance at operational machine guarding stations. This
      article develops a machine guard usage compliance model. Nonetheless, very few
      studies account for operator compliance to the usage of machine guards in
      workplaces. METHODS: This article contributes by first building up a multiple
      regression (MR) model, and, second, proposing a novel integrated MR and Taguchi
      method (MR-TM) model that optimizes operator compliance to guard usage. The
      comparative significance of the diverse factors was appraised and examined via
      analysis of variance. RESULTS: Bottling process data from Nigeria illustrate the
      effectiveness of the proposed model. The coefficient of determination (R2 =
      0.997) established the efficient predictive ability of the MR model. The
      significant variables are the number of functional guards and damaged guards, and
      the number of non-compliances (guards present and operational but not used) (p <
      0.050). Simulated and field data variables exhibited good agreement (R2 = 0.997).
      From the MR-TM model, the most significant result is the highest operator
      compliance for machine guard usage with mean and signal-to-noise ratio values of
      269.28 and 48.60, respectively. CONCLUSION: This work provides safety managers
      with snapshot information for planning and control purposes.

PMID- 30199319
TI  - In-group comparison is painful but meaningful: The moderator of classroom ethnic
      composition and the mediators of self-esteem and school belonging for upward
      comparisons.
AB  - This study examined the moderation of classroom ethnic composition and the
      mediation of group identification in the relationships between upward
      comparisons, depression, and self-efficacy in a sample of 359 Taiwanese
      aboriginal students. A stronger negative effect was found in highly ethnically
      concentrated classes. Upward comparisons were found to reinforce depression,
      decrease self-esteem, and reduce school belonging in aborigines-only classes but
      not in mainstream classes. Two pathways-self-esteem and school belonging-were
      found to process the negative indirect effects on depression and academic and
      social self-efficacy. The indirect effect through school belonging was
      particularly strong in the aborigines-only classes compared with the mainstream
      classes. The suppression effect showed that when self-esteem and school belonging
      were sustained, the aboriginal students in aborigines-only classes could increase
      their social self-efficacy through upward comparisons.

PMID- 30199320
TI  - Levels of organochlorine pesticides in Amazon turtle (Podocnemis unifilis) in the
      Xingu River, Brazil.
AB  - Due to the toxicity and high environmental persistence of organochlorine
      pesticides in aquatic organisms, turtles have been studied as environment
      biomonitors. These animals are important sources of protein for the riverside and
      indigenous peoples of the Brazilian amazon. In the present study, organochlorine
      pesticide contamination was investigated in Podocnemis unifilis. Liver, muscle
      and fatty tissue samples were removed from 50 specimens collected from five
      sampling points located in the Xingu River basin. Fourteen organochlorine
      pesticides were analysed via gas chromatography with an electron capture detector
      (CG-ECD). Eight organochlorine pesticides were detected with average
      concentrations of ?DDT, ?Endossulfan and ?HCH which were 26.17 +/- 26.35, 14.38
      +/- 23.77 and 1.39 +/- 8.46 ng g-1 in moisture content, respectively. DDT
      compounds were the most predominant, with a greater concentration of pp'-DDT in
      the liver and pp'-DDD in the muscle. Significant differences were noted between
      the types of tissues studied, and the concentration of OCPs varied between
      sampling sites.

PMID- 30199321
TI  - Microwave enhanced advanced oxidation treatment of dairy manure.
AB  - The microwave enhanced advanced oxidation process (MW-AOP) was used to treat
      dairy manure in a continuous-flow 915 MHz microwave wastewater treatment system.
      The treatment efficiency increased with an increase in temperature, as well as
      hydrogen peroxide dosage. The settling property was also improved in all treated
      sets, regardless of temperature applied. The system operated at temperatures >100
      degrees C had a much higher soluble chemical oxygen demand than at temperatures
      <100  degrees C. The highest soluble carbonaceous compounds, orthophosphate and
      ammonia were obtained at 110  degrees C and 0.6%H2O2 per % of total solids
      content. The process should be operated at higher temperatures and higher
      hydrogen peroxide dosages for maximizing solids disintegration, nutrient release
      and energy efficiency. An energy fingerprint correlating the cumulative energy
      consumption and temperature rise was developed. The results demonstrated that the
      custom designed MW-AOP system is suitable for the effective treatment of dairy
      manure. The system can readily be scaled up and integrated into a dairy farm
      manure treatment and resource recovery system.

PMID- 30199323
TI  - Effects of carbon source, C/N ratio, nitrate, temperature, and pH on N2O emission
      and functional denitrifying genes during heterotrophic denitrification.
AB  - The effects of operational parameters such as carbon source, C/N ratio, initial
      nitrate concentration, temperature, and pH value on heterotrophic denitrification
      and functional denitrifying genes were evaluated. When methanol was used as the
      sole carbon source, complete denitrification was performed in a short time
      without nitrous oxide (N2O) emission. Complete denitrification was performed at
      high C/N ratios (5.14 and 12.85) and low initial nitrate concentrations (75.9 and
      151.6 mg N L-1). The denitrification rate was not temperature-sensitive in the
      range of 25-35  degrees C, but tended to decrease at a low pH of 5-6. The
      relationships between N2O emission and functional genes under various operational
      conditions were investigated by Pearson correlation and association network
      analyses. The C/N ratio was a key factor for N2O emission during the
      heterotrophic denitrification process. This information on the denitrification
      performance and its association with functional gene dynamics under various
      operational conditions is useful for N2O mitigation strategies for wastewater
      treatment processes.

PMID- 30199322
TI  - MHC-associated peptide proteomics enabling highly sensitive detection of
      immunogenic sequences for the development of therapeutic antibodies with low
      immunogenicity.
AB  - Immunogenicity is a key factor capable of influencing the efficacy and safety of
      therapeutic antibodies. A recently developed method called MHC-associated peptide
      proteomics (MAPPs) uses liquid chromatography/mass spectrometry to identify the
      peptide sequences derived from a therapeutic protein that are presented by major
      histocompatibility complex class II (MHC II) on antigen-presenting cells, and
      therefore may induce immunogenicity. In this study, we developed a MAPPs
      technique (called Ab-MAPPs) that has high throughput and can efficiently identify
      the MHC II-presented peptides derived from therapeutic antibodies using magnetic
      nanoparticle beads coated with a hydrophilic polymer in the immunoprecipitation
      process. The magnetic beads could identify more peptides and sequence regions
      originating from infliximab and adalimumab in a shorter measurement time than
      Sepharose beads, which are commonly used for MAPPs. Several sequence regions
      identified by Ab-MAPPs from infliximab corresponded to immunogenic sequences
      reported by other methods, which suggests the method's high potential for
      identifying significant sequences involved in immunogenicity. Furthermore, our
      study suggests that the Ab-MAPPs method can recognize the difference of a single
      amino acid residue between similar antibody sequences with different levels of T
      cell proliferation activity and can identify potentially immunogenic peptides
      with high binding affinity to MHC II. In conclusion, Ab-MAPPs is useful for
      identifying the immunogenic sequences of therapeutic antibodies and will
      contribute to the design of therapeutic antibodies with low immunogenicity during
      the drug discovery stage.

PMID- 30199324
TI  - Treatment of concentrated leachate with low greenhouse gas emission in two-stage
      membrane bioreactor bio-augmented with Alcaligenes faecalis no. 4.
AB  - Methane (CH4) and nitrous oxide (N2O) emissions from two-stage membrane
      bioreactor (MBR) bio-augmented by Alcaligenes faecalis no. 4 during municipal
      solid waste leachate treatment were investigated. The system was operated at
      hydraulic retention time (HRT) of 2.5 and 1 days in each reactor under the
      presence and absence of sludge recirculation. Alcaligenes faecalis no. 4 bio
      augmentation helped improving organic carbon and nitrogen removals while reducing
      CH4 and N2O emissions. CH4 and N2O emissions were decreased by 46% and 85% when
      A. faecalis no. 4 was introduced at HRT of 2.5 days. Under the presence of A.
      faecalis no. 4, the operation of two-stage MBR with sludge recirculation could
      reduce CH4 and N2O emissions by 51% and 54% as compared to its operation without
      sludge recirculation. An operation under short HRT of 1 day also yielded high
      organic carbon and nitrogen removals of more than 85% while emitting lower CH4
      and N2O emission of 6.7% C and 0.04% N when operated with sludge recirculation.
      Implications: A two-stage membrane bioreactor was effectively applied to the
      treatment of concentrated leachate (BOD~20,000 mg/L) at a short hydraulic
      retention time of 2.5 days and 1 day. About 80% of CH4 and N2O was emitted from
      the anaerobic and aerobic reactors, respectively. Introduction of Alcaligenes
      faecalis no. 4 reduced CH4 and N2O emissions in both reactors as it became the
      predominant microorganism under an elevated pH condition. Lower CH4 and N2O
      emissions were achieved under a sludge recirculation operation, as Alcaligenes
      faecalis no. 4 could suppress methanogenic activities in the anaerobic reactor
      and converted a majority of nitrogen into its cell mass, thus reducing N2O
      production through a biological nitrification-denitrification pathway.

PMID- 30199325
TI  - Identification and phylogenetic analysis of clade C Avipoxvirus in a fowlpox
      outbreak in exotic psittacines in southern Brazil.
AB  - Fowlpox is one of the oldest diseases reported in birds. The causative genus
      Avipoxvirus affects ~232 domestic and wild species. We present herein the
      history, clinical findings, and macroscopic and histologic lesions caused by a
      clade C poxvirus in an exotic psittacine breeding colony in southern Brazil.
      Clinical signs included yellow nodular lesions at the commissure of the beak and
      on the periocular skin, loss of appetite, and death. Fifty birds were autopsied,
      and fragments of periocular skin, tongue, and trachea were examined
      histologically, which revealed hyperkeratosis associated with eosinophilic
      intracytoplasmic inclusion bodies. Tracheal fragments and periocular skin were
      subjected to nested PCR and phylogenetic analyses. The sequenced strain showed
      99.58% identity with the nucleotide sequences of Avipoxvirus strains AY53011,
      KC018069, AM050383, and AM05382 isolated from birds in Germany, United States,
      and United Kingdom. The strain was grouped under clade C, which represents
      isolates exclusively from the Psittacidae family. The infection caused by clade C
      Avipoxvirus in the exotic psittacines examined ( Platycercus sp. and Psephotus
      haematonotus) demonstrates the circulation of this clade in this breeding colony.

PMID- 30199326
TI  - Effect of ozonization in degradation of trifluralin residues in aqueous and food
      matrices.
AB  - This study investigates the oxidation of trifluralin residues during ozonation in
      aqueous and food matrices (tomato). Domestic ozonation equipment with average
      production of 23.9 mg O3 L-1 h-1 was used in the tests. Modern chromatographic
      systems (SPME-GC-IT/MS/MS and QuEChERS-GC-IT/MS/MS) were applied for extraction
      and detection of trifluralin residue in fortified samples of ultrapure water, tap
      water, superficial water and tomato fruit. The samples were submitted to the
      ozonation process during 0, 5, 10 and 20 min. Treatment at 5 min was able to
      degrade 71.5% of herbicide trifluralin in surface water. The removal (%) in
      ultrapure water reached 83.4% after 20 min of ozonation. The degradation of
      trifluralin in fortified tomato samples (0.025-0.1 mg kg-1) were conducted with
      ozonation at 20 min, and it ranged from 84.4 to 92.7%. After treatment, levels of
      trifluralin in tomato remained within the established MRLs to EU, USEPA and
      ANVISA (Brazil). The data provided evidence that ozone is effective for removing
      trace trifluralin from water and foods.

PMID- 30199327
TI  - Genotypic and Pathogenic Diversity of Colletotrichum sublineola Isolates from
      Sorghum (Sorghum bicolor) and Johnsongrass (S. halepense) in the Southeastern
      United States.
AB  - Anthracnose caused by Colletotrichum sublineola is an important disease of
      cultivated sorghum (Sorghum bicolor) worldwide. Anthracnose is also common on the
      ubiquitous wild sorghum relative Johnsongrass (S. halepense). Analysis of
      repetitive molecular fingerprinting markers revealed that isolates of C.
      sublineola from both hosts in the southeastern United States were genotypically
      diverse, with relatively few haplotypes found in more than one location. With few
      exceptions, isolates recovered from S. bicolor belonged to a population that was
      genetically distinct from the population recovered from S. halepense. Twenty
      three isolates from cultivated sorghum were all pathogenic to at least one of 13
      heritage inbred lines of S. bicolor. In all, 4 of 10 isolates from S. halepense
      were also pathogenic to one or more of the lines, while the rest caused no
      disease in greenhouse assays. The four pathogenic isolates from S. halepense were
      less aggressive, on average, than isolates from S. bicolor, although the ranges
      overlapped. Pathogenicity tests involving 15 representative pathogenic isolates
      from S. bicolor and S. halepense on eight heritage inbred lines of S. bicolor
      identified 12 races. The combined results of this study demonstrated that C.
      sublineola comprises two separate host-associated subpopulations in the field,
      even though some isolates from S. halepense were able to cause disease on S.
      bicolor under ideal greenhouse conditions. Nonetheless, the apparent existence of
      infrequent cross-infection events in the field, indicated by molecular
      fingerprinting, suggests that Johnsongrass has the potential to serve as a refuge
      and an incubator for genetic diversity in C. sublineola, which can complicate
      efforts to develop and deploy resistant sweet sorghum varieties in the region.

PMID- 30199328
TI  - Systematic reviews and meta-analyses of human and animal evidence of prenatal
      diethylhexyl phthalate exposure and changes in male anogenital distance.
AB  - Male reproductive alterations found in animals and humans following in utero
      phthalate exposure include decreased anogenital distance (AGD) and other
      reproductive-tract malformations. The aim of this investigation was to conduct
      systematic reviews of human and animal evidence of the effect of in utero
      exposure to diethylhexyl phthalate (DEHP) on anogenital distance (AGD) in males.
      PubMed, Embase, and Toxline were searched for relevant human and experimental
      animal studies on August 15, 2016. Search results were screened for relevance,
      and studies that met the inclusion criteria were evaluated for quality and data
      extracted for analysis. Confidence in the human and animal bodies of evidence was
      assessed and hazard conclusions reached by integrating evidence streams. The
      search yielded 6 relevant human studies and 19 animal studies. Meta-analysis of 5
      human observational prospective cohort studies showed that increased maternal
      urinary concentrations of DEHP metabolites were associated with decreased AGD in
      boys (-4.07 [CI, -6.49 to -1.66] % decrease per log10 rise in DEHP metabolites).
      Meta-analysis and meta-regression of the 19 experimental animal studies found
      reduced AGD with DEHP treatment, with a dose-response gradient, and with
      heterogeneity explained by species and strain. There is a moderate level of
      evidence from human investigations and a high level of data from animal studies
      that in utero exposure to DEHP decreases AGD. Based upon the available human and
      animal evidence, and consideration of mechanistic data, DEHP is presumed to be a
      reproductive hazard to humans on the basis of effects on AGD.

PMID- 30199329
TI  - Boron inhibits aluminum-induced toxicity to citrus by stimulating antioxidant
      enzyme activity.
AB  - Aluminum (Al) toxicity is a major factor limiting plant productivity. The
      objective of the present study was to develop the mechanisms of boron (B)
      alleviating aluminum toxicity in citrus. The results showed that aluminum
      toxicity severely hampered root elongation. Interestingly, under aluminum
      exposure, boron supply improved superoxide dismutase activity while reducing
      peroxidase, catalase and polyphenol oxidase activities. Likewise, the contents of
      H2O2, lipid peroxidation, protein and proline in roots were markedly decreased by
      boron application under aluminum exposure. Our results demonstrated that boron
      could alleviate aluminum toxicity by regulating antioxidant enzyme activities in
      the roots.

PMID- 30199330
TI  - Characteristics and Outcome of Twenty-Nine Implant-Related Infections of the Hand
      and Fingers: Results from a Twelve-Year Observational Study.
AB  - BACKGROUND: Implant-related infections in hand surgery are dreaded complications,
      potentially leading to loss of finger joint function or amputation. Knowledge
      about the clinical presentation and treatment concepts of these infections is
      limited. The aim of this study is to present a consecutive series of patients
      with implant-related infections of the finger joints and wrist. PATIENTS AND
      METHODS: We identified 25 patients with 29 implant-related infections. Infections
      were categorized as osteosynthesis-related infections (ORIs) or arthroplasty
      related infections (ARIs). Further categorization included early and late post
      operative (four weeks or less or more than four weeks after implantation) and
      exogenous and hematogenous infection. RESULTS: Compared with patients with ARIs
      (n = 11), those with ORIs (n = 14) were predominantly male (n = 11), were younger
      (mean 43 vs. 65 years, p = 0.0023), had few or no comorbidities, and had an
      exogenous source of infection. Patients with ARIs were predominantly female with
      rheumatoid arthritis (n = 8) and had a hematogenous pathogenesis. Infections
      occurred late in 22 (88%) patients. The most commonly isolated micro-organism was
      Staphylococcus aureus (n = 12; 48%). All ORIs were treated with implant removal
      and a median antimicrobial treatment duration of 39 days (interquartile range
      [IQR] 28-50 days). In the ARI group, the implant was removed in three patients
      and exchanged in three patients (one-stage exchange in one patient, two-stage
      exchange in two patients). In five individuals, debridement and implant retention
      was performed. The median antimicrobial treatment duration for ARIs was 42 days
      (IQR 30-75 days). The median follow-up time was 96 days (IQR 42-258 days) and
      infection was cured or presumably cured in 22 patients (88%). CONCLUSION: Our
      series shows distinct host and clinical patterns in ORIs and ARIs, supporting
      this categorization. The infection prognosis in ORIs is excellent with implant
      removal and antimicrobial treatment. Treatment concepts in ARIs are often derived
      from algorithms for periprosthetic joint infections of larger joints and need to
      be further elucidated.

PMID- 30199332
TI  - Family Group Conferencing as a Catalyst for Recovery and Ownership in Mental
      Health.
AB  - BACKGROUND: Recovery is a journey not only of personal change but also of social
      reengagement. It underlines the essence of social environments that are
      supportive to the recovery of people with ongoing mental health issues. The
      process of recovery also affects other actors, and likewise these actors exert
      their influence on the recovery of their family member or friend. OBJECTIVE:
      Since 2009, we have been studying whether the decision-making model called family
      group conferencing (FGC) helps mental health clients increase their self
      reliance. The essence of FGC is that individuals who experience problems have the
      opportunity to develop a plan together with people from their social network.
      Clients in mental health have to deal with different forms of disempowerment,
      especially when they are threatened with compulsory measures. It is an aim to
      help them regain ownership over their problems as well as over the potential
      solutions. METHOD: From 2011 to 2013, we evaluated 41 family group conferences
      that were organized for clients in a public mental health care setting in the
      north of the Netherlands. Each conference was analyzed in a qualitative case
      study framework. RESULTS: This article highlights two case portraits. It gives
      insight into how ownership was restored and what this meant regarding clients'
      recovery process. CONCLUSION: FGC seems a promising tool to shift the attention
      from disorders and inabilities to capacities and the rediscovery of social
      resources.

PMID- 30199331
TI  - Concentrations of aliphatic and polycyclic aromatic hydrocarbons in ambient PM2.5
      and PM10 particulates in Doha, Qatar.
AB  - Organic carbon (OC), elemental carbon (EC) and ninety organic compounds (36
      polycyclic aromatic hydrocarbons (PAHs), 25 n-alkane homologues, 17 hopanes and
      12 steranes) were concurrently quantified in atmospheric particulate matter of
      PM2.5 and PM10. The 24-hr PM samples were collected using Harvard Impactors at a
      sub-urban site in Doha, Qatar from May to December 2015. The mass concentrations
      (mean +/- standard deviation) of PM2.5 and PM10 were 40 +/- 15 and 145 +/- 70 ug
      m-3, respectively, exceeding the World Health Organization (WHO) air quality
      guidelines. Coarse particles comprised 70% of PM10. Total carbonaceous contents
      accounted for 14% of PM2.5 and 10% of PM10 particulate mass. The major fraction
      (90%) of EC was associated with the PM2.5. Conversely, 70% of OC content was
      found in PM2.5-10 fraction. The secondary OC accounted for 60-68% of the total OC
      in both PM fractions, indicating photochemical conversions of organics are much
      active in the area having higher air temperatures and solar radiations. Among the
      studied compounds, n-alkanes were the most abundant group, followed by PAHs,
      hopanes, and steranes. n-alkanes from C25 to C35 prevailed with a predominance of
      odd carbon numbered congeners (C27-C31). High-molecular-weight PAHs (5-6 rings)
      also prevailed, within their class, with benzo[b + j]fluoranthene (Bb+ jF) being
      the dominant member. PAHs were mainly (by 80%) associated with the PM2.5
      fraction. Local vehicular and fugitive emissions were predominant during low
      speed southeasterly winds from urban areas, while remote petrogenic/biogenic
      emissions were particularly significant under prevailing northwesterly wind
      conditions.

PMID- 30199333
TI  - Mechanistic ecotoxicology and environmental toxicology.

PMID- 30199334
TI  - Dissipation and translocation of saisenxin in tobacco and soil under conventional
      field and controlled laboratory conditions.
AB  - The aim of this investigation was to investigate the fate and translocation
      characteristics of saisenxin (SSX), a novel organic zinc fungicide, in the
      environment and tobacco plants under conventional field and laboratory
      conditions. A rapid and sensitive analytical technique based on high-performance
      liquid chromatography was used for determination of SSX, in soil samples and
      tobacco leaf, stem and root samples. The method had satisfactiry linearity (R2 =
      0.9999) and the limits of detection and of quantitation of the target compound
      were 0.06 and 0.20 mg kg-1, respectively. The average recoveries were in the
      range of 89.74-94.24% in soil, leaf, stem and root samples, with relative
      standard deviations of <8%. For conventional field trials, the half-life (t1/2)
      of SSX was 5.9-6.5 days in soil and 4.8-5.3 days in tobacco leaves; the
      corresponding values under controlled laboratory conditions were extended to 7.1
      and 7.6 days. The translocation factor (TF) values were in the range of 0-2.25
      and 0-0.25 for foliage and root irrigation treatments, respectively. The TFs of
      SSX in tobacco indicated that tobacco had a high ability to transfer SSX upward.

PMID- 30199335
TI  - Analysis of mineral oil in food: results of a Belgian market survey.
AB  - Recently, migration of mineral oil components from food contact materials into
      various foods has been reported. The analysis of mineral oil in food is
      complicated since it consists of mineral oil saturated hydrocarbons (MOSH)
      comprising a complex mixture of linear, branched and cyclic compounds and
      variable amounts of mineral oil aromatic hydrocarbons (MOAH), mainly alkylated.
      Both MOSH and MOAH form 'humps' of unresolved peaks in the chromatograms with the
      same range of volatility. Since these two fractions have a different
      toxicological relevance, it is important to quantify them separately. Occurrence
      data on mineral oil are available only for a limited number of food groups and
      only from few countries. In Belgium, data on the contamination of food by mineral
      oil are lacking. In this contribution, an in-house validated online combination
      of liquid chromatography with gas chromatography (LC-GC) with flame ionisation
      detection (FID) was used for the quantification of MOSH and MOAH. Totally, 217
      packed food samples were selected using a well-defined sampling strategy that
      targeted food categories which are highly consumed and categories suspected to
      contain mineral oil. For 19 samples, the method was not applicable. For the 198
      remaining samples, MOSH was detected in 142 samples with concentrations up to
      84.82 mg kg-1. For the MOAH fraction, there are 175 samples with a concentration
      below the limits of quantification (LOQ), while 23 samples had a higher
      concentration ranging from 0.6 to 2.24 mg kg-1. Finally, these results were
      compared with the action thresholds as proposed by the Scientific Committee
      (SciCom) of the Belgian Food Safety Agency (FAVV-AFSCA). Only one sample exceeded
      the threshold for MOSH, while the threshold for MOAH was exceeded in 23 samples.
      For the samples exceeding the action threshold, further investigation is needed
      to identify the contamination source.

PMID- 30199336
TI  - Processes in Psychotherapy and the MATRIX: The Case of Projective Identification.
AB  - The MATRIX is a tool designed to analyze psychoanalytic sessions. It is composed
      of two axes: focus (patient, therapist, and dyad) and dimension (space, content,
      and order). The MATRIX was found to be a reliable tool, and valid for identifying
      the therapist's theoretical inclinations in psychoanalytic-oriented psychotherapy
      sessions. In the present study, we suggest that the MATRIX can identify different
      (Kleinian, Bionian, and relational) approaches to projective identification, thus
      providing therapists and supervisors an easy-to-use tool for monitoring, and
      better managing, projective identifications during psychoanalytically oriented
      psychotherapy.

PMID- 30199337
TI  - Teaching Psychotherapy to Psychiatry Residents.
AB  - The rationale, content, and teaching techniques used for a psychiatry residency
      psychodynamic therapy course based on Psychodynamic Therapy: A Guide to Evidence
      Based Practice (Summers & Barber, 2009) are presented in the context of their
      evolution over the last two decades and the challenges of teaching this topic in
      the current environment. The central elements of an exciting and engaging
      psychotherapy teaching program-feelings, framework, and freedom-are explained.
      Specific topics such as psychodynamic formulation, using videos, self-disclosure,
      and resistance are discussed.

PMID- 30199338
TI  - Editorial: Psychiatric Ethics and the Goldwater Rule.

PMID- 30199339
TI  - Interview with Bandy Lee.

PMID- 30199340
TI  - Personality Organization, Personality Styles, and the Emotional Reactions of
      Treating Clinicians.
AB  - This study explores the relationship between clinicians' emotional reactions and
      patients' level of personality organization and personality style assessed
      according to the Psychodynamic Diagnostic Manual-2 (Lingiardi & McWilliams,
      2017). Level of personality pathology was positively associated with helpless and
      overwhelmed responses and negatively with positive responses. Parental and
      disengaged responses were associated with schizoid, anxious and dependent
      personalities. Parental and criticized responses were associated with
      narcissistic personalities; their depressed versions were positively associated
      with parental reactions, but negatively with positive reactions. Parental and
      overwhelmed responses were associated with counter-dependent and passive
      aggressive dependent personalities; the latter also with criticized reactions.
      Disengaged responses were associated with depressive personalities, particularly
      with their introjective subtypes, obsessive-compulsive and somatizing
      personalities. Overwhelmed reactions were associated with relational self
      defeating and hysterical/histrionic personalities, the latter also with
      sexualized reactions. Sexualized and helpless reactions were connected to
      hypomanic personalities. Findings show that emotional reactions can be useful for
      understanding personality features.

PMID- 30199341
TI  - Mimicking the host regulation of SA: a virulence strategy by the clubroot
      pathogen Plasmodiophora brassicae.
AB  - The plant hormone salicylic acid (SA) plays a critical role in defense against
      biothrophic pathogens such as Plasmodiophora brassicae (Pb) which is an obligate
      pathogen of crucifer species and the causal agent of clubroot disease of canola
      (Brassica napus). Pb encodes a protein, predicted to be secreted, with very
      limited homology to benzoic acid (BA)/SA -methyltransferase (MT) designated
      PbBSMT. PbBSMT has a SA- and an IAA-binding domain, which are also present in
      Arabidopsis thaliana BSMT1 (AtBSMT1), and these domains in PbBSMT methylate BA
      and SA. In support of the hypothesis that Pb uses PbBSMT to overcome SA-mediated
      defenses by converting SA into inactive methyl salicylate (MeSA), here we show
      that PbBSMT suppresses local defense and provide evidence that PbBSMT is much
      more effective than AtBSMT1 at suppressing the levels of SA and its associated
      effects. Basal SA levels in Arabidopsis plants that constitutively overexpressing
      PbBSMT compared to those in Arabidopsis wild type Col-0 (WT) were reduced
      approximately 80% verses only a 50% reduction in plants overexpressing AtBSMT1.
      PbBSMT-overexpressing plants were more susceptible to Pb than WT plants; they
      also were partially compromised in non-host resistance to Albugo candida. In
      contrast, AtBSMT1 response to either Pb or A. candida was similar to the control
      WT Col. Furthermore, transgenic Arabidopsis and tobacco plants overexpressing
      PbBSMT exhibited increase susceptibility to virulent Pseudomonas syringae pv.
      tomato DC3000 and virulent P. syringae pv. tabaci, respectively. R-gene mediated
      resistance to PstDC3000/AvrRpt2 and TMV was also compromised in Arabidopsis and
      Nicotiana tabacum cv. Xanthi-nc plants overexpressing PbBSMT, respectively.
      Transient expression of PbBSMT or AtBSMT1 in lower leaves of Nt Xanthi-nc
      resulted in systemic acquired resistance (SAR)-like enhanced resistance to TMV in
      the distal systemic leaves. Chimeric grafting experiments revealed that similar
      to SAR, the development of PbBSMT-mediated SAR-like phenotype was also dependent
      on the MeSA esterase activity of NtSABP2 in the systemic leaves. Collectively,
      these results strongly suggest that PbBSMT is a novel effector, which is secreted
      by Pb into its host plant to deplete pathogen-induced SA accumulation.

PMID- 30199342
TI  - Intravesical lidocaine decreases autonomic dysreflexia when administered prior to
      catheter change.
AB  - OBJECTIVE: To evaluate the role of intravesical lidocaine in preventing autonomic
      dysreflexia (AD) during routine catheter changes in individuals with spinal cord
      injury (SCI) at T6 or above. DESIGN: Prospective observational cohort study.
      SETTING: Outpatient urology clinic. PARTICIPANTS: Fifty consecutive individuals
      with SCI at or above T6 and a history of AD having a routine indwelling catheter
      change. INTERVENTIONS: A treatment group of individuals received 10 ml of 2%
      lidocaine administered into the existing catheter 4-6 minutes prior to catheter
      change. The control group had the same amount of lidocaine administered into the
      urethra or suprapubic tract after removing the old catheter and immediately prior
      to inserting the new catheter (due to the delayed onset of action of the
      anesthetic, this was assumed to have no initial effect). Systolic blood pressures
      (SBP) were measured immediately after catheter insertion and then every 30-45
      seconds for 5 minutes. OUTCOME MEASURES: Incidence and magnitude of AD as
      determined by SBP following catheter change. RESULTS: The incidence of AD in the
      lidocaine treatment group was 14.8% vs 47.8% in the control group (P = .011).
      Pretreatment with lidocaine also demonstrated a significantly attenuated rise in
      SBP immediately after the catheter change (9.5 mmHg vs 26.9 mmHg for post
      treatment, P = .014) relative to baseline SBP. CONCLUSION: In individuals with
      SCI at risk of AD, pretreatment with intravesical lidocaine prior to catheter
      change significantly decreased both the incidence and magnitude of AD. This
      suggests that pretreatment with intravesical lidocaine is helpful in individuals
      with SCI who are prone to AD.

PMID- 30199343
TI  - Application of molecular imaging technology in neurotoxicology research.
AB  - Molecular imaging has been widely applied in preclinical research. Among these
      new molecular imaging modalities, microPET imaging can be utilized as a very
      powerful tool that can obtain the measurements of multiple biological processes
      in various organs repeatedly in a same subject. This review discusses how this
      new approach provides noninvasive biomarker for neurotoxicology research and
      summarizes microPET findings with multiple radiotracers on the variety of
      neurotoxicity induced by toxic agents in both the rodent and the nonhuman primate
      brain.

PMID- 30199344
TI  - Translating a spinal cord injury self-management intervention for online and
      telehealth delivery: A community-engaged research approach.
AB  - OBJECTIVE: To develop educational content and pilot test the use of tablet
      computers (iPads), online content management platform (iTunes U) and video
      conferencing (FaceTime) for delivery of a peer supported, spinal cord injury self
      management intervention, using a community-engaged research approach. DESIGN:
      Cross-sectional convenience sampled pilot study; evaluation using a combination
      of observation and questionnaires. SETTING: Community-based. PARTICIPANTS:
      Individuals with SCI (n = 10) recruited from the community. INTERVENTIONS:
      Participants engaged in a hands-on evaluation of the educational content and
      technology. OUTCOME MEASURES: Usability and acceptability of educational content
      and technology. RESULTS: Participants were receptive and satisfied with the iPad
      and iTunes U platform and the video chat experience. Statements by our
      participants demonstrated a clear preference for interactive and multimedia
      platforms to promote engagement with educational materials. The use of FaceTime
      to facilitate contact between the participant and PN demonstrated satisfactory
      usability and acceptability. The hands-on evaluation process highlighted the need
      for consideration of connectivity for rural participants and assistive technology
      needs. CONCLUSION: Our community-engaged research approach and evaluation
      processes provided direct user feedback on the online and telehealth
      implementation of PHOENIX that will guide development of the remaining
      educational content, and testing of the intervention in a future feasibility
      trial.

PMID- 30199345
TI  - Growth, photosynthesis and removal responses of the cyanobacteria Chroococcus sp.
      to malathion and malaoxon.
AB  - Malathion is an organophosphorus pesticide widely used in agricultural crops,
      despite its toxicity. In addition, malaoxon occurs by oxidation of malathion
      being more toxic. The toxic effects of malathion and malaoxon in humans include
      hepatoxicity, breast cancer, genetic damage and endocrine disruption. The aim of
      this study involved assessing the effect of malathion commercial grade on
      Chroococcus sp., and its potential as an alternative to the removal of this
      pesticide and its transformation product such as malaoxon. We evaluated the
      effect of malathion at different concentrations (1, 25, 50, 75 and 100 ppm) on
      the biomass of the cyanobacteria Chroococcus sp. grown in medium BG-11; also, we
      analyse its ability to degrade both malathion and malaoxon into a temperature of
      28 +/- 2  degrees C and at pH 6. The results showed that 50 ppm of malathion the
      cyanobacteria Chroococcus sp. reached the highest removal efficiency of malathion
      and malaoxon (69 and 65%, respectively); also, the growth rate of Chroococcus sp.
      increased without inhibiting the production of chlorophyll "a", this can be
      explained by the hormesis phenomenon. Therefore, we consider that the
      cyanobacteria Chroococcus sp. may be a good candidate for bioremediation of
      aquatic systems contaminated with organophosphorus pesticides such as malathion
      and its transformation product such as malaoxon.

PMID- 30199346
TI  - Anxiety masquerading as autonomic dysreflexia.
AB  - CONTEXT: Autonomic dysreflexia (AD) is characterized by a sudden onset of
      hypertension in those with spinal cord injuries (SCI) at T6 or above. Prompt
      recognition and treatment of AD is important. Herein are two individuals with SCI
      and acute hypertension due to anxiety that may easily have been confused for AD.
      FINDINGS: Case 1: A 77-year-old male with C4 AIS D SCI and a history of anxiety
      and AD presented for urodynamics to evaluate the effectiveness of
      onabotulinumtoxinA injections into his urethral sphincter. After lying down on
      the urodynamics table, his systolic blood pressure (SBP) was noted to rise, from
      138 to 170 mmHg over six minutes without any instrumentation or position change.
      Upon announcing urodynamics would be postponed and preparing for AD management,
      his SBP returned to below baseline within two minutes. Case 2: A 57-year-old male
      with T12 AIS A SCI and a history of anxiety presented for routine urodynamics.
      His baseline SBP was 140 mmHg. During bladder filling, incidental SBP was
      elevated to 170 mmHg. Filling was stopped and he was told the study was complete.
      One minute later, prior to draining his bladder, SBP decreased to 150 mmHg.
      CONCLUSIONS: An individual's psychological state should be considered in addition
      to traditional management of AD when an individual with SCI presents with
      hypertension. Moreover, Case 2 may possibly explain reports of individuals
      presenting with AD with injuries below T6.

PMID- 30199347
TI  - Force Increase in a Repetitive Motor Task Inducing Motor Fatigue.
AB  - To evaluate task induced motor fatigue in a well-established finger tapping task,
      we analyzed tapping parameters and included the time course of measures of force.
      We hypothesized that a decline in tapping force would reflect task induced motor
      fatigue, defined by a lengthening of inter-tap intervals (ITI). A secondary aim
      was to investigate the reliability of tapping data acquisition with the force
      sensor. Results show that, as expected, tapping speed decreased linearly over
      time, due to both an increase of ITI and tap duration. In contrast, tapping force
      increased non-linearly over time and was uncorrelated to changes in tapping
      speed. Force data could serve as a measure to characterize task induced motor
      fatigue. Force sensors can assess a decline in tapping speed as well as an
      independent increase of tapping force. We argue that the increase of force
      reflects central compensation, i.e. perception of fatigue, due to an increase in
      task effort and difficulty.

PMID- 30199348
TI  - Targeted Temperature Management: Peltier's Element-Based Focal Brain Cooling
      Protects Penumbra Neurons from Progressive Damage in Experimental Cerebral
      Ischemia.
AB  - Targeted temperature management (TTM), or therapeutic hypothermia, is one of the
      most potent neuroprotective approaches after ischemic and traumatic brain
      injuries. TTM has been applied clinically with various methods, but effective
      achievement and maintenance of the target temperature remain challenging.
      Furthermore, timing of cooling and target body and brain temperature to optimize
      effectiveness for neuroprotection and to minimize side effects are yet to be
      standardized. Focal brain cooling is a potential strategy to minimize adverse
      effects of systemic TTM. In this study, we report on a focal brain cooling device
      for animals and its effectiveness of focal cooling in several animal models of
      ischemic cerebral stroke. A focal brain cooling device was constructed using a
      Peltier's element, a thermoelectric heat pump. The device was validated for its
      cooling ability, and optimal settings to induce an effective intracranial
      temperature were determined using male Sprague-Dawley rats. Transient and
      permanent middle cerebral artery occlusions were experimentally induced, and
      focal brain cooling was applied using the device varying the timing and duration
      of cooling. The stroke-induced infarct and edema volumes were evaluated from
      Nissl-stained cryosections. The focal brain cooling device was able to decrease
      and subsequently maintained cerebral hypothermia in free-moving rats without
      altering the core temperature. The device with validated intracranial
      temperatures produced neuroprotective effects in the acute phase of ischemic
      neural death, reperfusion injury, progressing damage to the penumbra, and edema
      formation. In conclusion, our validated focal cooling device enabled rapid and
      accurate cerebral TTM in rats. Using this device, we were able to test the
      neuroprotective effect of focal TTM in several pathological stages of cerebral
      ischemia, which warrants further studies to develop clinically feasible TTM
      procedures for patients with cerebral stroke.

PMID- 30199349
TI  - For the Little Queers: Imagining Queerness in "New" Queer Children's Literature.
AB  - This article identifies and analyzes an emerging archive of children's picture
      books that represent transgender and gender creative child characters. The
      subgenre of children's literature is referred to as new queer children's
      literature. The author explores the ways these texts represent queer youth as
      they negotiate various social institutions, especially the family and the school.
      It is suggested that an ambivalent reading of these images-one neither committed
      to anti-normativity nor assimilation-can help us understand the queer present at
      its most affirmative and, by extension, aid us in beginning to theorize possible
      queer futures.

PMID- 30199350
TI  - Toward evidence-based anti-human trafficking policy: a rapid review of CSE
      rehabilitation and evaluation of Indian legislation.
AB  - This paper (a) examines the evidence base around rehabilitation of victims of
      trafficking for commercial sexual exploitation (CSE), (b) identifies the extent
      that India's proposed 2016 Trafficking of Persons (Prevention, Protection, and
      Rehabilitation) Bill reflects scientific and experiential evidence, and (c)
      discusses how gaps in the proposed bill can be informed by evidence. A rapid
      review of empirical studies on policies and interventions addressing
      rehabilitation of CSE victims was conducted. Although evidence is lacking,
      research suggests that cross-sectoral collaboration, training and monitoring law
      enforcement, psychotherapeutic interventions and care provided by short-term
      shelters, reintegration, and recognizing victims' rights improve the success of
      rehabilitative efforts. The proposed legislation does not sufficiently reflect
      evidence around successful rehabilitation efforts and suggests that implementing
      the bill as it currently stands would change little of the existing structures to
      support victims in receiving adequate services or successfully reintegrating into
      society.

PMID- 30199352
TI  - D-dimer monitoring combined with ultrasonography improves screening for
      asymptomatic venous thromboembolism in acute spinal cord injury.
AB  - OBJECTIVE: We compared screening methods for asymptomatic venous thromboembolism
      (VTE) in patients with acute spine and spinal cord injuries (SCI). Patients were
      screened by D-dimer monitoring alone (DS group) or by D-dimer monitoring combined
      with ultrasonography (DUS group). DESIGN: Prospective cohort study. SETTING: One
      department of a university hospital in Japan. PARTICIPANTS: 114 patients treated
      for acute SCI between 2011 and 2017. INTERVENTIONS: N/A. OUTCOME MEASURES: D
      dimers were measured upon admission and 1, 3, 5, 7, and 14 days thereafter. DUS
      group patients also underwent an ultrasound 7 days after admission. If
      ultrasonography indicated deep venous thrombosis (DVT), or if D-dimer levels
      increased to >= 10 ug/mL, the patient was assessed for VTE, including DVT or
      pulmonary embolism (PE), by contrast venography. We analyzed the incidence of VTE
      detected in the DS and DUS groups. RESULTS: In the DS group, D-dimers were
      elevated (>= 10 ug/mL) in 15 of 70 patients (21.4%), and 9 of the 15 had
      asymptomatic VTE (12.9%, DVT 11.4%, PE 5.7%). In the DUS group, one patient
      developed VTE on day 4, and D-dimers were elevated in 13 of 43 patients (30.2%),
      ultrasonography indicated DVT in 12 patients (27.9%), and asymptomatic VTE was
      diagnosed in 12 patients (27.9%, DVT 27.9%, PE 4.7%). The DUS group had a higher
      incidence of DVT (P = 0.002) and VTE (P = 0.042) than the DS group. CONCLUSIONS:
      Combined D-dimer and ultrasound screening in patients with acute SCI improved the
      detection of VTE, including PE, compared with D-dimer screening alone.

PMID- 30199351
TI  - Making and sustaining change from psychotherapy: A mixed methods study.
AB  - This study explored both how changes are made and what encourages the maintenance
      of change after psychotherapy, from the perspective of a sample of former
      clients, using a mixed methods sequential design. Wampold & Imel's (2015)
      contextual model was used as a conceptual framework. Using secondary data
      analysis, quantitative analysis was used to explore the degree to which clients
      made and maintained progress from pretest to post test and 12 to 18 month follow
      up. Fourteen interviews were used to hear from former clients about their
      impressions of what supported their efforts at change and how they maintained
      these gains post treatment. The findings of the quantitative strand demonstrated
      clinically meaningful change from pretest to follow-up, using a 1 x 3 repeated
      measures ANOVA. Qualitative themes emerged in response to questions asking about:
      what facilitates change, what participants do to maintain changes, and what
      characterized clinical relationships that did and did not go well.

PMID- 30199353
TI  - Eye of the beholder? Observation versus self-report in the measurement of
      disrespect and abuse during facility-based childbirth.
AB  - Human rights has been a vital tool in the global movement to reduce maternal
      mortality and to expose the disrespect and abuse that women experience during
      childbirth in facilities around the world. Yet to truly transform the
      relationship between women and providers, human rights-based approaches (HRBAs)
      will need to go beyond articulation, dissemination and even legal enforcement of
      formal norms of respectful maternity care. HRBAs must also develop a deeper, more
      nuanced understanding of how power operates in health systems under particular
      social, cultural and political conditions, if they are to effectively challenge
      settled patterns of behaviour and health systems structures that marginalise and
      abuse. In this paper, we report results from a mixed methods study in two
      hospitals in the Tanga region of Tanzania, comparing the prevalence of disrespect
      and abuse during childbirth as measured through observation by trained nurses
      stationed in maternity wards to prevalence as measured by the self-report upon
      discharge of the same women who had been observed. The huge disparity between
      these two measures (baseline: 69.83% observation vs. 9.91% self-report; endline:
      32.91% observation vs. 7.59% self-report) suggests that disrespect and abuse is
      both internalised and normalised by users and providers alike. Building on
      qualitative research conducted in the study sites, we explore the mechanisms by
      which hidden and invisible power enforces internalisation and normalisation, and
      describe the implications for the development of HRBAs in maternal health.

PMID- 30199354
TI  - Determination of 16 PAHs and 22 PCBs in honey samples originated from different
      region of Lebanon and used as environmental biomonitors sentinel.
AB  - In order to assess the air quality in some Lebanese regions, a biomonitoring
      study based on honey as biomonitor candidate was conducted. For this, 18 samples
      of honey collected from four regions in Lebanon, were analyzed for their
      contamination by 16 polycyclic aromatic hydrocarbons (PAHs) and 22
      polychlorinated biphenyls (PCBs). Samples were first extracted using a multi
      residue extraction method based on the quick, easy, cheap, effective, rugged, and
      safe extraction method (QuEChERS) followed by a concentration step using Solid
      phase microextraction (SPME) procedures. The extraction was then followed by
      chromatographic analysis by gas chromatography-ion-trap tandem mass spectrometry
      (GC-MS/MS). After PAHs samples assessment, different ratios of founded PAHs were
      calculated in order to estimate the sources of the pollution by these compounds.
      The obtained results showed that the four analyzed regions were contaminated with
      PAHs originated from both pyro and petro genic sources while none of them was
      found to be contaminated by any of the 22 assessed PCBs. The results of this
      study show that honey can be used as potential biomonitor candidate allowing the
      assessment of the pollution statement of a given environment.

PMID- 30199356
TI  - [Updating pediatric neurology V. Introduction].

PMID- 30199355
TI  - Allophilia: Increasing college students' "liking" of older adults with dementia
      through arts-based intergenerational experiences.
AB  - This study evaluates whether an arts-based intergenerational experience, Opening
      Minds through Art (OMA), increases positive attitudes or allophilia ("liking for
      the other"-in this case, older adults with dementia) in students who joined the
      OMA program as compared with the control group. Pre- and posttests of the
      Allophilia Scale were used to compare 216 students who participated in OMA and
      499 students who did not. Hierarchical regression was used to investigate the
      association between OMA participation and students' Allophilia scores. After one
      semester, results showed that OMA participation is significantly positively
      associated with students' affection, comfort, kinship, engagement, and enthusiasm
      toward older adults living with dementia. We conclude that increasing students'
      allophilia toward older adults living with dementia is necessary and possible
      through well-designed intergenerational experiences.

PMID- 30199357
TI  - [Transional syndrome: from West to Lennox-Gastaut syndromes].
AB  - West syndrome or infantile spasms is an epileptic encephalopathy, classified as
      generalized epilepsies and syndromes. There are multiple reports of the evolution
      from West to Lennox-Gastaut syndrome of 25 up to 60%, without a specific cause is
      determined. It has been reported that they may be only an epileptic entity age
      dependent that it would be in relation to the degree of brain immaturity. In this
      retrospective review of 130 cases of West syndrome, only 14 (10.7%) evolved to
      Lennox-Gastaut. Having received in all cases vigabatrin as a treatment, makes us
      suppose that the low incidence could be related to the use of this drug. Given
      that vigabatrin has a gabaergic action and increased levels of ACTH, may explain
      this relationship but this must be confirmed with the best knowledge of the
      intimate mechanisms of these serious epileptic encephalopathies.

PMID- 30199358
TI  - [Evaluation of a child with a first unprovoked seizure].
AB  - Paroxysmal episodes are one of the most common neurological disorders in
      children. It is important to distinguish between paroxysmal non-epileptic events,
      symptomatic seizures, febrile seizures, and unprovoked seizures. Patient's
      history is the key to proper diagnosis in most of the cases. A single unprovoked
      seizure is a frequent phenomenon in the pediatric population. Studies of
      recurrence after a first unprovoked seizure show percentages between 23% and 96%
      over a median follow-up of two years. The aim of this study is to define how to
      evaluate the first unprovoked epileptic seizure in a child and to review the
      weight of the different recurrence risk factors. Several factors enable us to
      predict the recurrence risk after a first unprovoked seizure including family
      history of epilepsy, prior history of febrile seizures, age at onset, type of
      seizure, prolonged seizures at onset, multiple seizures in a single day, sleep
      state, neurological abnormalities, etiology, and abnormalities in the
      electroencephalogram. The most important of these risk factors are the etiology
      of the seizures and the evidence of epileptiform abnormalities in the
      electroencephalogram.

PMID- 30199359
TI  - [Status epilepticus].
AB  - Status epilepticus (SE) is one of the most common neurologic emergencies in
      pediatrics. It is a condition resulting either from the failure of the mechanisms
      responsible for seizure termination or from the initiation of mechanisms, which
      leads to abnormally, prolonged seizures. This definition provides a good
      guidance, when emergency treatment must be considered. In general, time point t1
      is the time when treatment should be started, which is at 5 minutes for
      generalized tonic-clonic seizures, and at 10 min for focal seizures with or
      without impairment of consciousness. Time-point t2 marks the time at which
      neuronal damage or self-perpetuating alteration of neuronal networks may begin
      and indicates that SE should be controlled latest by that time; 30 min in case of
      generalized tonic-clonic seizures. All treatment protocols recognize a staged
      approach to treatment with different drugs used in early (stage I), established
      (stage II), refractory (stage III) and super-refractory SE (stage IV); and
      emphasize prompt recognition and treatment of persisting seizure activity at each
      stage aiming to reduce morbidity, mortality, and long-term consequences of status
      epilepticus (beyond t2).

PMID- 30199360
TI  - [Febrile seizures: questions and answers].
AB  - A febrile seizure occurs in association with fever in a child aged 6 to 60
      months, without central nervous system infection or other known cause of acute
      seizures in a child without a prior history of afebrile seizures. Febrile
      seizures occur in about 2-5% of children. Central nervous system infections
      should be considered in patients with febrile seizures, even though the frequency
      of this possibility is low, especially when patients do not return to baseline.
      Simple febrile seizures are considered benign events and there are clear
      guidelines about evaluation and management, but the evaluation of complex febrile
      seizures is controversial. They are associated with a small increased risk of
      epilepsy which cannot be prevented. The role of electroencephalography is
      controversial. We analyzed the data of many studies and concluded that
      epileptiform discharges have poor positive predictive value. Neuroimaging is
      recommended to look for acute or pre-existing hippocampal abnormalities following
      febrile status or focal febrile seizures that could be associated to the risk of
      developing mesial temporal sclerosis and temporal lobe epilepsy. The relationship
      between these disorders and febrile seizures remains a controversial issue. An
      abnormal electroencephalography or magnetic resonance imaging studies will not
      change the clinical management and could contribute to overdiagnosis.

PMID- 30199361
TI  - [Neonatal seizures. Clinical and electroencephalographic diagnosis].
AB  - Neonatal seizures are common expression of acute brain injury in the perinatal
      period and could potentiate the degree of neuronal injury. The majority of events
      are electroencephalographic and the clinical seizures can be subtle and difficult
      to identify by medical personnel. Neonatal seizures are usually short and
      frequent at onset and have a tendency to subside after a short period. Continuous
      video-EEG monitoring is the gold standard to detect seizures, but amplitude
      integrated EEG is a useful tool when conventional EEG is not available. EEG
      monitoring is important not only to monitor frequency and duration of seizures
      but to provide important prognostic information.

PMID- 30199362
TI  - [Treatment of neonatal seizures].
AB  - Neonatal seizures are among the most dramatic manifestations of acute central
      nervous system dysfunction. The incidence is much higher in very low weight
      neonates than in full term infants (~ 58 and 3.5 per 100 live births,
      respectively). Neonatal seizures represent the clinical manifestation of a non
      specific cortical cerebral dysfunction which can lead to permanent brain injury.
      The etiology is multifactorial and requires a judicious assessment for each
      clinical scenario. The diagnosis is further complicated by the fact that most
      neonatal seizures are subclinical, that is, may display very subtle or no
      clinical changes and the diagnosis may just be based on EEG findings. The
      treatment depends on the etiology, but an early and opportune intervention
      prevents further brain damage, thus improving prognosis. Although early
      identification and treatment are critical, the diagnosis of neonatal seizures is
      complicated by several factors such as different clinical presentations, possible
      etiologies and several treatment options. Nevertheless, research studies and
      clinical evidence have shown that early treatment with anti-seizure medications
      can change the outcome.

PMID- 30199363
TI  - [Neonatal hypoxic-ischemic encephalopathy].
AB  - Hypoxic-ischemic encephalopathy is a clearly recognizable clinical syndrome of in
      term newborns due to fetal asphyxia at birth. The incidence is 1.5 (95% CI 1.3 to
      1.7) but it ranges from 1-8 and 25 out of every 1000 born in developed and
      developing countries, respectively. The most frequent causes are detachment of
      the placenta, prolapse of the umbilical cord and uterine rupture. The diagnostic
      criteria include partial or total incapacity for the newborn to cry and breath at
      birth even when stimulated, requiring assisted ventilation in the delivery room,
      Apgar < 5 in 5 and 10 minutes, acidemia (pH <= 7 and / or bases deficit >= 12
      mmol/l), alterations of the conscience and the reflexes of Moro, grasping and
      suction, muscular stretching and muscle tone. The clinical forms are mild,
      moderate and severe. In the mild forms, the recovery is total in three days
      without, or with minimal, neurodevelopmental alterations. The moderate and severe
      forms cause permanent neurological deficits and neurodevelopmental alterations
      (48%) or death (27%). The regular or amplitude integrated EEG and the magnetic
      and spectroscopic magnetic resonance imaging performed between 24 and 96 hours
      and 7 and 21 days after birth, respectively, have a high diagnostic and
      prognostic value. Induced hypothermia (33.5 degrees  C for 72 hours) is
      recommended before 6 hours old. The result is a decrease in mortality (from 35%
      to 27%) and morbidity (from 48% to 27%).

PMID- 30199364
TI  - [Non-epileptic paroxysmal disorder in neonates].
AB  - Non-epileptic paroxysmal disorders are frequent events in the neonate, generally
      transient. However, due to their intensity they can be confused as true epileptic
      seizures. The objective of this review is to update the concepts in relation to
      tremors, neonatal benign sleep myoclonus (MNBS) and hyperekplexia. The tremors
      are very frequent, once identified it must be determined if they belong to a
      hyperexcitability syndrome related to maternal or perinatal factors, in
      idiopathic cases a good prognosis is expected. MNBS are often confused with
      epileptic seizures. They are characterized by the fact that myoclonus is brief
      and occurs only in sleep, children are normal, and the EEG is also normal.
      Hyperekplexia is a rare, genetically determined disorder characterized by
      hypertonia and exaggerated startle reactions to a banal stimulus, which can be
      improved with clonazepam.

PMID- 30199366
TI  - [Non-epileptic paroxysmal disorders in pre-school children].
AB  - Paroxysmal events are commonly encountered in toddlers. These events include a
      variety of conditions with different manifestations and pathophysiology. For that
      reason, the diagnosis of these events can be challenging. In some instances,
      studies such as EEG and polysomnogram may be useful to differentiate between
      epileptic and non-epileptic events. In the majority of cases, a complete clinical
      history is enough to make an appropriate diagnosis. In this article, we review
      some of the most common paroxysmal non-epileptic events affecting toddlers, such
      as: tics, dyskinesias, sleep related events, etc. We also discuss diagnostic
      strategies and treatment options.

PMID- 30199365
TI  - [Non-paroxysmal disorder in infant].
AB  - Non-epileptic paroxysmal disorders (PNED) are defined as events that mimic
      epileptic seizures. Its onset is usually sudden and short-lived, caused by brain
      dysfunction of various origins, but not due to excessive neuronal firing. Its
      incidence is higher than the epilepsy (10:1). They can occur at any age but are
      most common in children, especially in the first year of life. The immature
      nervous system in childhood causes in this period, paroxysmal manifestations that
      are very diverse and different from other ages. Normal and common paroxysmal
      disorders in children can mimic epileptic seizures. The first step is to
      establish a correct diagnosis, if the clinical paroxysmal episode is a seizure or
      PNED. Differential diagnosis is very broad, especially in the first ages. It's
      necessary a complete neurological examination in case of doubt and the study
      should be extended with complementary exams, investigations that in most cases
      will be normal/negative. In some of them, a genetic basis has been shown.
      Treatment options are limited and most PNED untreated have a favorable outcome.

PMID- 30199367
TI  - [Attention deficit hyperactivity disorder beyond adolescence. Time to think
      different?]
AB  - ADHD is a neurodevelopmental disorder characterized by a pattern of severe
      inattention-disorganization and/or hyperactivity-impulsivity beyond what is
      expected for individuals with a comparable development level. These behaviors
      impair daily life activities of patients in more than one environment and impact
      their performance and abilities compared with their peers. Extensive reviews have
      been published about the psychiatric comorbidities associated with ADHD but
      little attention has been given to the overall impact of ADHD on health. This
      study reviews some of the most common problems in medical care associated with
      ADHD like smoking, substance use, accident risk, sleep disorders, obesity,
      hypertension, diabetes, and early mortality. Today, a close follow-up of patient
      with ADHD is necessary not only from the psychiatric perspective but also in
      regard to general medicine issues to prevent the impact on health of those
      medical co-morbidities. Such conditions can end in severe chronic diseases with
      consequences and high cost for the individuals, the families and the society far
      beyond the academic and emotional impact frequently described as associated to
      ADHD. This condition has serious repercussions on health which need a medical
      multidisciplinary approach.

PMID- 30199369
TI  - [Aging in people with autism spectrum disorder].
AB  - Autism spectrum disorder is characterized by a qualitative alteration in social
      interaction and communication associated with restricted interests and
      stereotyped behaviors. This condition will accompany people throughout their
      lives, with variations in their evolution. Our objectives were to know the
      evolutionary characteristics of people with autistic spectrum disorder, analyzing
      cognitive, behavioral, health, mortality and their needs in the aging stage,
      which will guide the planning of specific support resources. We analyze studies
      related to the evolution in adult life in people with this disorder, with or
      without identified entities, and socio-health conditions that should be
      considered in the aging process. The knowledge about aging in people with autism
      is still scarce and it is difficult to define a specific pattern because this
      will depend, among other factors, on the etiology, the degree, the presence of
      intellectual disability and/or epilepsy, and the scope in where live, which can
      even condition the life expectancy. Aging has been associated with mood
      disorders, depression, deterioration in executive functions and episodic memory,
      although it is difficult to differentiate it from natural aging in people with
      typical development. The identification of a specific entity will allow to know
      the possible evolution and prevent complications in syndromes that may be
      associated with autism: fragile X, Down, Angelman, Rett and Williams, for that
      reason we rank the genetic and neurological consultation.

PMID- 30199368
TI  - [Intellectual developmental disability overlapping with autism spectrum disorder
      and attention deficit-hyperactivity disorder].
AB  - The subject of disabilities that include cognition and adaptability will never
      cease to be interesting and relevant. The genetic etiology has more weight every
      day. The relationship with other neurodevelopmental disorders such as autism
      spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) is of
      clinical, diagnostic and therapeutic importance. The objective was to conduct a
      review of intellectual development disorder and its implication with ASD and
      ADHD. From Hippocrates to the present the disorders that affect learning,
      behavior and socialization skills have been the subject of studies and have
      varied, above all, in the denomination as an entity and its perception from the
      human and social point of view. The etiology of intellectual development
      disorders in most cases is an enigma and genetic advances are the cornerstone to
      elucidate the origin of this neurodevelopmental disorder, as well as its
      relationship with others such as ASD and ADHD. The disorder of intellectual
      development, the oldest one with respect to definition, study and approach, still
      presents mysteries above all of etiological origin. Its relationship with other
      neurodevelopmental disorders such as ASD and ADHD is evident by having common
      areas of involvement, which may be coincident diagnoses.

PMID- 30199370
TI  - [Demyelinating disorders].
AB  - Demyelinating diseases are a group of conditions of autoimmune etiology directed
      against the myelin of the central nervous system. In many cases, the onset of the
      illness is preceded by a nonspecific viral infection. Multiple sclerosis is a
      disease that evolves with relapses and remissions with polyfocal neurological
      deficits, being the most frequent optic neuritis, transverse myelitis and
      encephalic trunk involvement. Typically, magnetic resonance image (MRI) shows
      peri-ventricular, peri-callosal, cerebellum, brain stem and spinal cord
      hyperintensive lesions in T2 and FLAIR weighted images. Optic neuromyelitis is
      characterized by the presence of optic neuritis and transverse myelitis
      associated with the postrema and diencephalic area syndrome. MRI lesions are
      distributed in sectors rich with aquaporine-4 channels (AQP-4): hypothalamus,
      third and fourth ventricle, optic nerves and spinal cord. Finding anti AQP4
      antibodies is useful for the diagnosis although they are not essential for it.
      Acute disseminated encephalomyelitis is typically a monophasic condition
      characterized by acute encephalopathy associated with hyperintense MRI large,
      bilateral and irregular asymmetric lesion in T2 and FLAIR weighted images. In all
      three cases, cerebral spine fluid (CSF) can show pleocytosis and
      hyperproteinorrachia. The presence of oligoclonal bands in CSF is characteristic
      of multiple sclerosis. In all cases, acute treatment includes high dose
      intravenous corticosteroids and plasmapheresis in non-responsive cases. Both
      multiple sclerosis and optic neuromyelitis require long-term treatment to prevent
      relapse and recurrent diseases.

PMID- 30199371
TI  - [Peripheral nervous system immunological disorder].
AB  - Autoimmune diseases of the peripheral nervous system are common in pediatrics.
      Guillain-Barre syndrome, juvenile myasthenia gravis, and juvenile dermatomyositis
      are the most important. Their common pathogenesis involves the action of specific
      autoantibodies which are frequently triggered by viral or bacterial infection.
      Acute inflammatory demyelinating polyneuropathy is the most frequent pathological
      feature. There is also a motor axonal form. Both have a progressive ascending
      clinical course. The specific treatment is immunoglobulin 2 g/kg. Juvenile
      myasthenia gravis is expressed by ocular signs and generalized and fluctuating
      fatigability. It can involve respiratory functions triggering a myasthenic
      crisis. It is treated with anticholinesterase agents, corticosteroids,
      immunoglobulins, and immunosuppressants. Thymectomy has recently shown
      effectiveness. Juvenile dermatomyositis is expressed by skin and muscle signs.
      Elevated muscle enzymes, muscle biopsy, and magnetic resonance imaging contribute
      to the diagnosis. It is treated with corticosteroids, immunoglobulins, and
      immunosuppressants. All three disorders, Guillain-Barre, juvenile myasthenia
      gravis, and juvenile dermatomyositis have a good prognosis.

PMID- 30199372
TI  - [Autoimmune encephalitis. New diagnosis for an old condition].
AB  - Autoimmune encephalitis is a new group of diseases of great clinical and
      therapeutic importance due to the good response in most cases to the
      immunomodulatory therapy indicated, with a large percentage of healing without
      significant neurological effects (cognitive, motor, seizures or involuntary
      movements). Since 2007, the presence of neuronal autoantibodies in the
      pathogenesis of this group of diseases has been demonstrated, with psychotic
      symptoms and involuntary movements as clinical markers of the disease. The
      present review emphasizes the crucial leap and change of paradigms arising after
      the discovery of these encephalitis associated with antibodies.

PMID- 30199373
TI  - [Microcephaly].
AB  - Microcephaly is defined as a head circumference more than two standard deviations
      below the mean for gender and age. It is an important neurological sign and
      predictor of future disability. One of its diagnostic difficulties lies in the
      ranks of the head circumference reference against which we measure each child.
      The WHO developed growth curves that could be used universally, topic on which
      there may be discrepancies. Recently, Zika virus epidemic demanded to review the
      criteria for the diagnosis of microcephaly. The classification of the
      microcephaly in congenital and postnatal makes it possible to define the
      etiology, the associated symptoms and the prognosis. The evaluation of a child
      with microcephaly requires a thorough analysis of its history, clinical
      examination and complementary studies. MRI is the first step in the etiologic
      research. Genetic causes forming part of a syndrome or not, and prenatal
      infections are the most frequent etiologies but in half of the cases, no cause is
      found. The comparative hybridization genomic array (array-CGH) and full exome
      sequencing are techniques that more and more help us in the evaluation of
      patients with microcephaly. Depending on the cause and severity, children with
      microcephaly may have different problems such as intellectual disabilities,
      development retardation, epilepsy, cerebral palsy, as well as vision and hearing
      disorders. The microcephaly requires a multidisciplinary approach both in its
      initial assessment as it is its post-program monitoring.

PMID- 30199374
TI  - [Macrocephaly in childhood].
AB  - In a wide spectrum of cases in childhood, macrocephaly does not carry a
      neurological risk, although a range of possibilities will have an impact on both
      the evolutionary and cognitive aspects of children. The previous happens in
      pathologies with progressive components, such as tumors or hydrocephalus, and in
      those cases in which the factor of the growth of the cephalic perimeter is given
      by structural components of the nervous system as it happens in megalocephaly. As
      in all other medical acts, the careful taking of the anamnesis, the appropriate
      neurological examination and the valuations of the neurodevelopment items can
      give a thorough orientation about the etiology and importance of the problem. The
      help of diagnostic aids as well as images will provide the other data to define
      the diagnosis and propose a treatment.

PMID- 30199375
TI  - [Synostosic and non-synostosic cranial deformities].
AB  - In the last decades alterations in the skull shape have increased at the expense
      of plagiocephaly, as consequence of the American Academy of Pediatrics
      recommendations to sleep the infant in the supine position. The clinician must
      differentiate between positional plagiocephaly and craniosynostosis, since if a
      cranial synostosis is proven, the therapeutic behavior will be potentially
      neurosurgical. Although three-dimensional skull tomography with bone window is
      the study of greater sensitivity and diagnostic specificity, the majority of
      cases can be confirmed by the clinic, reserving the radiography or ultrasound
      with a suture approach for doubtful cases. Craniosynostosis must be early
      referral to a craniofacial team to define the indication, opportunity and most
      appropriate surgical technique, in order to avoid future neurocognitive and
      psychosocial complications. Children with positional plagiocephaly regardless of
      the treatment of cranial deformity may have a higher risk of motor development
      delay. For correction, repositioning and physiotherapy are suggested in mild to
      moderate forms, reserving the use of cranial orthesis in severe forms.

PMID- 30199376
TI  - An open source benchmarked toolbox for cardiovascular waveform and interval
      analysis.
AB  - OBJECTIVE: This work aims to validate a set of data processing methods for
      variability metrics, which hold promise as potential indicators for autonomic
      function, prediction of adverse cardiovascular outcomes, psychophysiological
      status, and general wellness. Although the investigation of heart rate
      variability (HRV) has been prevalent for several decades, the methods used for
      preprocessing, windowing, and choosing appropriate parameters lacks consensus
      among academic and clinical investigators. Moreover, many of the important steps
      are omitted from publications, preventing reproducibility. APPROACH: To address
      this, we have compiled a comprehensive and open-source modular toolbox for
      calculating HRV metrics and other related variability indices, on both raw
      cardiovascular time series and RR intervals. The software, known as the PhysioNet
      Cardiovascular Signal Toolbox, is implemented in the MATLAB programming language,
      with standard (open) input and output formats, and requires no external
      libraries. The functioning of our software is compared with other widely used and
      referenced HRV toolboxes to identify important differences. MAIN RESULTS: Our
      findings demonstrate how modest differences in the approach to HRV analysis can
      lead to divergent results, a factor that might have contributed to the lack of
      repeatability of studies and clinical applicability of HRV metrics. SIGNIFICANCE:
      Existing HRV toolboxes do not include standardized preprocessing, signal quality
      indices (for noisy segment removal), and abnormal rhythm detection and are
      therefore likely to lead to significant errors in the presence of moderate to
      high noise or arrhythmias. We therefore describe the inclusion of validated tools
      to address these issues. We also make recommendations for default values and
      testing/reporting.

PMID- 30199377
TI  - Nursing-Related Smartphone Activities in the Italian Nursing Population: A
      Descriptive Study.
AB  - In this study, we describe smartphone-related activities for nurses' work and
      nonwork purposes; analyzed the differences between smartphone use and nurses'
      age, gender, and working environment; and observed the influences that personal
      digital devices have on nurses' performance. We conducted a cross-sectional and
      correlational study. A convenience sample of nurses was recruited, composed of
      256 nurses, mostly women (74.6%) younger than 30 years of age (59%). This study
      showed that the most frequent work-related smartphone activity was searching for
      work-related drug references. Smartphones also helped nurses reduce work-related
      stress and improve unit cohesion and teamwork. Younger nurses and male nurses
      were more likely than female nurses to use their digital devices during
      healthcare activities. In addition, 42% of nurses reported that they were
      distracted by the use of smartphones. If smartphones are used properly, they are
      certainly helpful tools for improving patient safety and enabling communication
      among healthcare staff. Otherwise, smartphones can constitute an important source
      of distraction and endanger patient safety.

PMID- 30199378
TI  - Validation of the A&D BP UA-1200BLE device for home blood pressure measurement
      according to the ISO 81060-2: 2013 standard.
AB  - OBJECTIVE: The aim of this study was to validate the UA-1200BLE device using the
      ISO 81060-2:2013 standard. MATERIALS AND METHODS: Individuals aged more than 12
      years were recruited from among the outpatients and volunteers of Jichi Medical
      University (Tochigi, Japan). Eighty-five patients were included in the final
      analyses. Validation was performed using the same-arm sequence protocol as per
      the ISO 81060-2:2013 standard. RESULTS: The device performed well against the
      standard; the mean and SD values for the differences between device and observed
      systolic and diastolic blood pressure values fulfilled both criterion 1 and
      criterion 2 of the standard (criterion 1: -2.62+/-6.89 and -0.90+/-6.63 mmHg,
      respectively; criterion 2: -2.65+/-5.36 and -0.91+/-6.12 mmHg, respectively). The
      Bland-Altman plots did not show any systematic variation in the error.
      CONCLUSION: The UA-1200BLE device had a high level of accuracy and fulfilled all
      ISO 81060-2:2013 standard requirements in adults with a wide range of arm
      circumference measurements. It is therefore suitable as a wireless blood pressure
      monitoring tool in patients with hypertension.

PMID- 30199379
TI  - Nasal challenges in allergen immunotherapy trials.
AB  - PURPOSE OF REVIEW: The nasal allergen challenge (NAC) model can be a valuable
      diagnostic tool for allergic rhinitis. Alongside its clinical use, NACs can be
      used as primary and secondary endpoints in studies evaluating allergen
      immunotherapy (AIT) products for allergic rhinitis treatment. This review will
      discuss the technical aspects of the NAC model and provide a summary of recent
      studies using NACs to assess existing and new AIT treatments. RECENT FINDINGS:
      Over the last 2 years, both titrated and single-dose nasal challenge protocols
      have been used to evaluate immunotherapies targeting grass, birch, house dust
      mite, and cat allergens. Early efficacy and dose-finding trials showed
      improvements in allergic symptoms and nasal tolerance to allergens after AIT
      treatment with standardized extracts or modified forms of whole allergen. NACs
      were also used in two proof-of-concept studies to illustrate the efficacy of
      intralymphatic immunotherapy with two concomitant allergens and subcutaneous
      immunotherapy with Fel d 1-specific IgG-blocking antibodies. SUMMARY: Along with
      existing therapies, nasal challenges are useful in evaluating AIT treatments in
      the very early stages of clinical development. However, because of the variety in
      challenge techniques and symptom assessments available, special attention must be
      placed in the protocol design in order to compare the study results with existing
      NAC publications.

PMID- 30199380
TI  - Radioaerosol Imaging Predicts the Utility of Aerosolized Antifungal Therapy in
      Allergic Bronchopulmonary Aspergillosis.
AB  - A 10-year-old girl with a history of complicated cystic fibrosis was hospitalized
      for pulmonary exacerbation with allergic bronchopulmonary aspergillosis and
      severe right upper lobe bronchiectasis diagnosed with chest radiograph and CT.
      She was started on itraconazole during the hospitalization in attempt to decrease
      her systemic steroid dose, but she had ongoing coughing and wheezing. The
      possibility was raised that the right upper lobe bronchiectasis may be a nidus
      for ongoing aspergillosis. Radioaerosol imaging was performed to determine
      whether the aerosolized antifungals would reach the area of bronchiectasis.

PMID- 30199382
TI  - Etanercept for Ankylosing Spondylitis With Coexisting Demyelinating Myelitis.

PMID- 30199381
TI  - SUV Harmonization Between Different Hybrid PET/CT Systems.
AB  - AIM: Current PET/CT lutetium oxyorthosilicate (LSO) or lutetium-yttrium
      oxyorthosilicate crystal scanners are equipped with sophisticated softwares
      including point-spread function (PSF) and time-of-flight (TOF) image
      reconstruction. These softwares are associated with increased SUVs compared with
      3D-OSEM reconstructions associated with older BGO PET/CT scanners. The European
      Association of Nuclear Medicine (EANM) identified the problem of SUV
      harmonization since 2010 through the EANM Research Ltd European Association of
      Nuclear Medicine Research Ltd [EARL] FDG PET/CT accreditation program. This
      required processing 2 reconstructions, one optimized for maximum spatial lesion
      detection and one for harmonized quantitation. We investigated an alternative
      single reconstruction method for both qualitative and quantitative analysis
      optimized to maximize spatial lesion detectability, followed by an intrinsic
      postreconstruction algorithm for SUV harmonization. METHODS: Phantom and "in
      vivo" patient data analysis were acquired and analyzed on (a) a Siemens Biograph
      mCT system with LSO crystals and PSF and TOF algorithms, and on (b) a General
      Electric Discovery STE system with BGO crystals, without PSF and TOF. A dedicated
      algorithm (EQ.filter) was tested to harmonize SUV between the 2 scanners compared
      with EANM/EARL specifications. NEMA IQ phantom and a Jaszczak cylindrical phantom
      equipped with small fillable spheres (lesion to background ratios of 8:1 and 4:1)
      were used. Phantom data were validated on 7 oncologic patients with 39
      hyperactive lesions ranging from 3 mm to 26 mm. RESULTS: The main benefit of PSF
      + TOF LSO PET/CT systems was increased contrast for small active lesions.
      Recovery coefficients measured according to NEMA standards exceeded those
      obtained by 3D-OSEM reconstruction. SUVmax discrepancies between the 2 PET/CT
      systems were as high as 149%, dropping to below 10% when optimized by EQ.filter.
      CONCLUSIONS: A single reconstruction optimized by EQ.filter for maximum spatial
      lesion detectability is an easy and precise solution to harmonize SUVs between
      different PET/CT scanners, avoiding a second reconstruction with an additional
      smoothing filter as requested by EANM/EARL.

PMID- 30199383
TI  - Impact of Antibiotic Treatment on 30-Day Readmissions for Community-Acquired
      Pneumonia.

PMID- 30199384
TI  - Home Is Where the HeartWare Is: Preparing Pediatric Patients and Caregivers for
      Discharge to Home and Integration Into the Community.
AB  - The Cardiac Center at The Children's Hospital of Philadelphia has cared for
      patients with implanted ventricular assist device (VAD) technology since 1998.
      Historically, patients requiring VAD support were managed exclusively in the
      Cardiac Intensive Care Unit with the first medically stable transition to the
      Cardiac Care Unit (step-down) taking place in 2001. Patient management was
      confined to the inpatient setting, as the primary device used at the time was
      paracorporeal and not suitable for home use. Continuous-flow devices, such as the
      HeartWare HVAD, have gained popularity because of miniaturized size and lower
      profiles of side effects and adverse events, making them more suitable for home
      use. This article describes a single-center experience with transitioning the VAD
      supported pediatric patient to the outpatient setting, highlighting outcomes,
      strategies, and lessons learned in order to support VAD patients and their
      caregivers in the hospital and community setting.

PMID- 30199386
TI  - Pediatric VAD Discharge and Outpatient Care.
AB  - The advancement of pediatric ventricular assist devices (VADs) has enabled
      pediatric centers to discharge VAD patients home and integrate them back into
      their communities. Creating standard work flow processes to ensure the
      educational needs of the patient, family, and community are met will enable
      programs to successfully manage VAD patients at home. Utilizing multidisciplinary
      teams to support these patients while hospitalized will greatly contribute to the
      patients and families readiness for discharge. Defining mutual goals and
      expectations for patients, families, and the VAD team will promote a superior
      discharge and outpatient experience.

PMID- 30199385
TI  - International Analysis of LVAD Point-of-Care Versus Plasma INR: A Multicenter
      Study.
AB  - International normalized ratio (INR) measurements manage risks of bleeding and
      clotting sequelae in the population with left ventricular assist device (LVAD).
      Studies suggest that point-of-care (POC) INR does not significantly differ from
      plasma INR (P-INR) values in other patient populations, although this has not
      been validated in a multicenter LVAD study. We sought to determine whether POC
      INR and P-INR values differ significantly in the LVAD population and reviewed
      patients with permanent LVAD implantation at seven institutions internationally.
      Our cohort comprised of 279 paired POC-INR and P-INR checks in patients supported
      on average 630 +/- 598 days postimplant with predominately HeartWare, HeartMate
      II, and HeartMate III devices. The population averaged 57.9 years of age, and
      there were 86.7% male. We found no statistically significant difference between
      POC-INR and P-INR values. International normalized ratio accuracy correlated
      weakly with the time between INR measurements (p < 0.001). When the time
      difference was less than 4 hours, the difference between INR pairs was
      significantly lower than measurements greater than 8 hours (p = 0.006). There was
      no statistically significant difference when comparing paired INR values and time
      after implant to INR check (p = 0.43), age (p = 0.12), known coagulopathy (p =
      0.12), bleeding history (p = 0.22), or thrombosis history (p = 0.34). This is the
      first large multicenter international study comparing POC-INR and P-INR
      measurements in patients with LVAD and found no statistically significant
      difference between either methods, particularly when measured within less than 4
      hours of each other.

PMID- 30199388
TI  - The acute effects of cannabis on human executive function.
AB  - Cannabis remains the most frequently used illicit drug worldwide. It produces a
      broad range of acute effects, such as euphoria, increased heart rate and
      perceptual alterations. Over the last few decades, a substantial number of
      experiments have been conducted to provide insight into the acute effects of
      cannabis on cognition. Here, we systematically review studies that investigated
      the impact of administration of cannabis or [INCREMENT]-tetrahydrocannabinol, the
      main psychoactive constituent of cannabis, on human executive function, in
      particular, on the three principal domains of inhibition, working memory and
      reasoning/association. Our findings suggest that cannabis use results in acute
      impairment of inhibition, with the strongest effects after pulmonary
      administration of higher doses of [INCREMENT]-tetrahydrocannabinol. Results from
      neuroimaging studies indicate that these effects are predominantly modulated
      through neural processes in the inferior frontal gyrus. Working memory and
      reasoning/association are less clearly affected by cannabis administration,
      possibly because of compensational neural mechanisms to overcome the effects of
      cannabis intoxication on performance accuracy. Factors that may account for the
      variation in results are the extent to which a paradigm involves attentional
      processes, differences between studies in administration methods and variation in
      the patients' history of cannabis use.

PMID- 30199389
TI  - Dopamine and serotonin antagonists fail to alter the discriminative stimulus
      properties of +/-methylenedioxymethamphetamine.
AB  - Most studies on discriminative stimulus effects of 3,4
      methylenedioxymethamphetamine (MDMA) have been conducted using a relatively low
      dose (1.5 mg/kg), and those studies have invariably implicated serotonergic
      mechanisms. In contrast, dopaminergic mechanisms mediate the discriminative
      stimulus effects of amphetamine (AMPH). Some studies have suggested that the
      discriminative stimulus effects of a higher (3.0 mg/kg) dose of MDMA might rely
      on both serotonergic and dopaminergic mechanisms. This study aimed to determine
      effects of selective dopamine (DA) and serotonin (5HT) antagonists on the
      discriminative stimulus properties of AMPH (0.5 mg/kg) and MDMA (3.0 mg/kg).
      Separate groups of rats were trained to discriminate AMPH (0.5 mg/kg) or MDMA
      (3.0 mg/kg) from saline using a food-reinforced drug-discrimination procedure.
      Effects of DA (SCH 23390: 0.003-0.03 mg/kg and eticlopride: 0.03-0.3 mg/kg) or
      5HT (ritanserin: 1.0-10.0 mg/kg, WAY-100635: 0.3-1.0 mg/kg and GR129375: 1.0-3.0
      mg/kg) antagonists on the discriminative stimulus effects of both drugs were
      determined. Both DA antagonists dose-dependently decreased the AMPH but not the
      MDMA discrimination. None of the 5HT antagonists altered the discriminative
      stimulus effects of either drug. The MDMA (3.0 mg/kg) stimulus comprises both a
      DAergic and 5HTergic response, and the results suggest that either one is
      sufficient, but not required, to maintain the stimulus effects.

PMID- 30199387
TI  - Physiological and Psychological Stress in Patients Living With a Left Ventricular
      Assist Device.
AB  - Patients with a left ventricular assist device (LVAD) commonly experience
      psychological distress post-implantation, but physiological stress and
      differences by implant strategy remain unstudied. This study describes indicators
      of physiological (salivary cortisol, C-reactive protein, sleep quality) and
      psychological (perceived stress, depression, and fatigue) stress by implant
      strategy and examines relationships between stress and outcomes (quality of life
      [QOL] and functional status). Prospective, cross-sectional data were collected
      from patients >=3 months post-LVAD implantation (n = 44), and descriptive
      statistics and logistic regression were used. The study sample was average age
      57.7 +/- 13 years, mostly male (73%), married (70.5%), and racially diverse.
      Median LVAD support was 18.2 months. Most had normal cortisol awakening response
      and fair sleep quality, with moderate psychological stress. There were no
      differences in stress by implant strategy. Normal cortisol awakening response was
      correlated with low depressive symptoms. Sleep quality and psychological stress
      were associated with QOL, whereas cortisol and C-reactive protein levels were
      associated with functional status. This is the first report of salivary
      biomarkers and stress in LVAD outpatients. Future research should examine
      physiological and psychological stress and consider potential clinical
      implications for stress measurement for tailored approaches to stress management
      in this population.

PMID- 30199390
TI  - Early Intervention to Improve Sucking in Preterm Newborns: A Systematic Review of
      Quantitative Studies.
AB  - BACKGROUND: Premature birth is associated with feeding difficulties due to
      inadequate coordination of sucking, swallowing, and breathing. Nonnutritive
      sucking (NNS) and oral stimulation interventions may be effective for oral
      feeding promotion, but the mechanisms of the intervention effects need further
      clarifications. PURPOSE: We reviewed preterm infant intervention studies with
      quantitative outcomes of sucking performance to summarize the evidence of the
      effect of interventions on specific components of sucking. METHODS: PubMed,
      CINAHL, MEDLINE, EMBASE, and PSYCOLIST databases were searched for English
      language publications through August 2017. Studies were selected if they involved
      preterm infants, tested experimental interventions to improve sucking or oral
      feeding skills, and included outcome as an objective measure of sucking
      performance. Specific Medical Subject Headings (MeSH) terms were utilized.
      RESULTS: Nineteen studies were included in this review: 15 randomized, 1 quasi
      randomized, and 3 crossover randomized controlled trials. Intervention types were
      grouped into 6 categories (i) NNS, (ii) NNS with auditory reinforcement, (iii)
      sensorimotor stimulation, (iv) oral support, (v) combined training, and (vi)
      nutritive sucking. Efficiency parameters were positively influenced by most types
      of interventions, though appear to be less affected by trainings based on NNS
      alone. IMPLICATIONS FOR PRACTICE: These findings may be useful in the clinical
      care of infants requiring support to achieve efficient sucking skills through NNS
      and oral stimulation interventions. IMPLICATIONS FOR RESEARCH: Further studies
      including quantitative measures of sucking performance outcome measures are
      needed in order to best understand the needs and provide more tailored
      interventions to preterm infants.

PMID- 30199391
TI  - ICU Management of Trauma Patients.
AB  - OBJECTIVES: To describe the current state of the art regarding management of the
      critically ill trauma patient with an emphasis on initial management in the ICU.
      DATA SOURCES AND STUDY SELECTION: A PubMed literature review was performed for
      relevant articles in English related to the management of adult humans with
      severe trauma. Specific topics included airway management, hemorrhagic shock,
      resuscitation, and specific injuries to the chest, abdomen, brain, and spinal
      cord. DATA EXTRACTION AND DATA SYNTHESIS: The basic principles of initial
      management of the critically ill trauma patients include rapid identification and
      management of life-threatening injuries with the goal of restoring tissue
      oxygenation and controlling hemorrhage as rapidly as possible. The initial
      assessment of the patient is often truncated for procedures to manage life
      threatening injuries. Major, open surgical procedures have often been replaced by
      nonoperative or less-invasive approaches, even for critically ill patients.
      Consequently, much of the early management has been shifted to the ICU, where the
      goal is to continue resuscitation to restore homeostasis while completing the
      initial assessment of the patient and watching closely for failure of
      nonoperative management, complications of procedures, and missed injuries.
      CONCLUSIONS: The initial management of critically ill trauma patients is complex.
      Multiple, sometimes competing, priorities need to be considered. Close
      collaboration between the intensivist and the surgical teams is critical for
      optimizing patient outcomes.

PMID- 30199392
TI  - Use of Vasopressor Increases the Risk of Mortality in Traumatic Hemorrhagic
      Shock: A Nationwide Cohort Study in Japan.
AB  - OBJECTIVES: To evaluate the possible association of vasopressor use with
      mortality in traumatic hemorrhagic shock patients. DESIGN: Retrospective cohort
      study. SETTING: Traumatic hemorrhagic shock patients at 260 emergency hospitals
      in Japan between 2004 and 2015. PATIENTS: Three-thousand five-hundred fifty-one
      traumatic hemorrhagic shock patients who had systolic hypotension (< 90 mm Hg) on
      arrival at the emergency department and a blood transfusion received within the
      first 24 hours. INTERVENTIONS: The use of vasopressor for traumatic hemorrhagic
      shock within the first 24 hours. MEASUREMENTS AND MAIN RESULTS: Among 236,698
      trauma patients, 3,551 were included in the study. Overall, 198 of 459 patients
      (43%) in the vasopressor+ group expired compared with 481 of 3,092 patients (16%)
      in the vasopressor- group. Use of vasopressor had an odds ratio of 2.172 (95% CI,
      1.666-2.833) for in-hospital mortality adjusted for age, gender, year of onset,
      cause of injury, mechanism of injury, vital signs at the emergency department,
      Injury Severity Score, use of prehospital IV fluid, and volume of blood
      transfusion within the first 24 hours. In the propensity score-matched cohort and
      two subgroup analyses (massive transfusion and survivable injury models), use of
      vasopressor was associated with higher mortality (odds ratio, 2.168; 95% C, 1.442
      3.320), (odds ratio, 2.029; 95% CI, 1.414-2.911; massive transfusion model), and
      (odds ratio, 1.959; 95% CI, 1.364-2.814; survivable injury model). CONCLUSIONS:
      Use of vasopressor for traumatic hemorrhagic shock was associated with mortality
      after controlling for biases (trauma severity; volume of fluid resuscitation).

PMID- 30199393
TI  - Beneficial effects of walnut consumption on human health: role of micronutrients.
AB  - PURPOSE OF REVIEW: Nuts in general and walnuts in particular are in the limelight
      for the association of their consumption with improved health outcomes. Walnuts
      have an optimal composition in bioactive nutrients and recent clinical and
      experimental studies have uncovered a number of beneficial effects of walnut
      micronutrients, working in isolation or in concert, on metabolic pathways and
      clinical outcomes that make this review timely and relevant. RECENT FINDINGS:
      Alpha-linolenic acid, a critical walnut component, is metabolized into bioactive
      oxylipins, has been shown to protect microglial cells from inflammation, and is
      associated with lower fatal myocardial infarction rates through a putative
      antiarrhythmic effect. Phytosterols relate to the cholesterol-lowering effect of
      nut consumption. Nonsodium minerals are associated with better cardiometabolic
      health. Walnut phytomelatonin has anticancer effects that are shared by the main
      walnut polyphenols and their metabolites, ellagitannins and urolithins,
      respectively. SUMMARY: This review highlights new evidence on the health
      promoting properties of walnuts and their main micronutrient components. The
      conclusion is that walnuts are optimal healthful foods.

PMID- 30199394
TI  - Crucifers and related vegetables and supplements for neurologic disorders: what
      is the evidence?
AB  - PURPOSE OF REVIEW: Neurologic disorders have varied pathophysiology, yet many of
      them appear to have core molecular pathways that are aberrant. We review the
      evidence that a dietary component may have utility in ameliorating or preventing
      at least some of them. RECENT FINDINGS: The weight of evidence supporting
      prescriptive dietary recommendations to promote or enhance healthspan has been
      building for decades. Cruciferous vegetables are a key part of the arsenal of
      nutrition-based approaches for reducing the burden of chronic disease. Much new
      evidence suggests that neurological disorders are among the potential targets for
      this approach. This evidence includes at least nine clinical studies of
      neurodevelopmental conditions like autism spectrum disorder and schizophrenia,
      and there are a great many studies in animal model systems, of neurodegenerative
      disorders like Alzheimer's and Parkinson's diseases. This review highlights the
      most bioactive and most well-studied compounds from crucifers - the
      isothiocyanates, in particular sulforaphane. SUMMARY: There is great promise for
      the regular use of cruciferous vegetables or supplements containing standardized
      levels of bioactives in the treatment and prevention of neurologic disorders.
      Many clinical and animal studies are underway, and the evidence is building to
      support this strategy.

PMID- 30199396
TI  - Cutaneous Lymphoproliferative Disorders: What's New in the Revised 4th Edition of
      the World Health Organization (WHO) Classification of Lymphoid Neoplasms.
AB  - Cutaneous lymphoproliferative disorders remain a challenging aspect of
      dermatopathology, in part due to the rarity of the entities and extreme
      variability in clinical outcomes. Although many of the entities remain unchanged,
      the approach to some of them has changed in the new 2016 classification scheme of
      the World Health Organization. Chief among these are Epstein-Barr virus
      associated lymphoproliferative disorders such as Epstein-Barr virus-associated
      mucocutaneous ulcer and hydroa vacciniforme-like lymphoproliferative disorder,
      primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma,
      primary cutaneous acral CD8+ T-cell lymphoma, primary cutaneous CD4+ small/medium
      T-cell lymphoproliferative disorder, and breast implant-associated anaplastic
      large cell lymphoma. In addition, translocations and gene rearrangements such as
      those involving the 6p25.3 locus have started to inform diagnosis and
      classification of anaplastic large cell lymphoma and lymphomatoid papulosis. In
      this review, we will examine what is new in the diagnostic toolbox of cutaneous
      lymphoproliferative disorders.

PMID- 30199395
TI  - RAS-expanded Mutations and HER2 Expression in Metastatic Colorectal Cancer: A New
      Step of Precision Medicine.
AB  - Cetuximab and panitumumab monoclonal antibodies are a milestone in the history of
      treatment of metastatic colorectal cancer (mCRC) and point toward future
      directions for personalized treatment. Recent studies have shown that broader RAS
      testing is needed to select patients for targeted therapy. The objectives of our
      study were to identify the prevalence of RAS mutations and evaluate human
      epidermal growth factor receptor 2 (HER2) expression in KRAS exon 2 wild-type
      (WT) mCRC patients, correlating the findings with objective response rate,
      progression-free survival, and overall survival. In total, 29 mCRC patients
      undergoing treatment with cetuximab therapy were enrolled in this study. By
      pyrosequencing, mutations were found in 17% of nonresponder patients, in KRAS
      codon 146 and NRAS codon 12. HER2 positivity was limited to only 1 responder
      carcinoma specimen. There was no correlation between RAS mutation, HER2/neu
      expression, and clinicopathologic findings. We highlighted significantly the
      differences between objective response rate and RAS gene status. The overall
      survival and progression-free survival of RAS WT patients were higher compared
      with those with RAS-mutated disease. Clinical response to cetuximab therapy is
      impaired in the presence of RAS-expanded mutations. In fact, our finding of 5
      mutations in RAS-expanded genes allowed us to understand the resistance to
      cetuximab in 33% of KRAS WT exon 2 nonresponder patients. HER2 does not seem to
      be a potential biomarker for cetuximab-targeted therapy. These analyses suggest
      that the assessment of other biomarkers is needed to determine the best treatment
      for patients with mCRC, to maximize benefit and minimize harm.

PMID- 30199397
TI  - Air- and Bone-Conducted Sources of Feedback With an Active Middle Ear Implant.
AB  - OBJECTIVES: Active middle ear implants (AMEI) have been used to treat hearing
      loss in patients for whom conventional hearing aids are unsuccessful for varied
      biologic or personal reasons. Several studies have discussed feedback as a
      potential complication of AMEI usage, though the feedback pathway is not well
      understood. While reverse propagation of an acoustic signal through the ossicular
      chain and tympanic membrane constitutes an air-conducted source of feedback, the
      implanted nature of the device microphone near the mastoid cortex suggests that
      bone conduction pathways may potentially be another significant factor. This
      study examines the relative contributions of potential sources of feedback during
      stimulation with an AMEI. DESIGN: Four fresh-frozen, hemi-sectioned, human
      cadaver specimens were prepared with a mastoid antrostomy and atticotomy to
      visualize the posterior incus body. A Carina active middle ear implant actuator
      (Cochlear Ltd., Boulder, CO) was coupled to the incus by two means: (1) a
      stereotactic arm mounted independently of the specimen and (2) a fixation bracket
      anchored directly to the mastoid cortical bone. The actuator was driven with pure
      tone frequencies in 1/4 octave steps from 500 to 6000 Hz. Acoustic sound
      intensity in the ear canal was measured with a probe tube microphone (Bruel &
      Kjaer, Naerum, Denmark). Bone-conducted vibration was quantified with a single
      axis laser Doppler vibrometer (Polytec Inc., Irvine, CA) from both a piece of
      reflective tape placed on the skin overlying the mastoid and a bone-anchored
      titanium screw and pedestal (Cochlear Ltd., Centennial, CO) implanted in the
      cortical mastoid bone. RESULTS: Microphone measurements revealed ear-canal
      pressures of 60-89 dB SPL, peaking in the frequency range below 2 kHz. Peak LDV
      measurements were greatest on the mastoid bone (0.32-0.79 mm/s with mounting
      bracket and 0.21-0.36 mm/s with the stereotactic suspension); peak measurements
      on the skin ranged from 0.05 to 0.15 mm/s with the bracket and 0.03 to 0.13 mm/s
      with stereotactic suspension. CONCLUSION: AMEI produce both air- and bone
      conducted signals of adequate strength to be detected by the implanted device
      microphone, potentially resulting in reamplification. Understanding the relative
      contribution of these sources may play an important role in the development of
      targeted mitigation algorithms, as well as surgical techniques emphasizing
      acoustic isolation.

PMID- 30199398
TI  - Acute Chemical Eye Injury and Limbal Stem Cell Deficiency-A Prospective Study in
      the United Kingdom.
AB  - PURPOSE: To analyze the incidence, nature, outcomes, and complications of acute
      chemical eye injuries, including the incidence of limbal stem cell deficiency
      (LSCD) and to compare the 2 main classifications for ocular chemical injuries:
      Roper-Hall (RH) and Dua. METHODS: This is a prospective, consecutive,
      interventional single-center study between April and October 2009 of all new
      patients with acute chemical eye injury presenting to the Royal Victoria
      Infirmary eye emergency department (EED). RESULTS: Of 11,683 patients who
      attended the EED, 98 patients (110 eyes) presented with acute chemical eye injury
      (60% male). This represents an estimated annual incidence of 5.6 new cases per
      100,000 population. Mean age was 36.5 years (1-78; SD 17.1 years), including 7
      children (age <10 years). Fifty-one patients (52%) had work-related injuries. The
      most common chemical agent was alkali (78%). All 4 RH grade IV cases were
      unilateral, assault with ammonia, and required early amniotic membrane
      transplantation as per the protocol, but despite full treatment, they developed
      total LSCD in the affected eye. CONCLUSIONS: Acute chemical eye injuries are
      rare. Male patients in the working age group are more prone to work-related
      chemical injuries, whereas young children tend to have domestic injuries. Grade
      I, II, and III RH and Dua chemical injuries had a very good prognosis with
      topical treatment only, whereas RH grade IV (Dua grade IV-VI), mainly assaults
      with ammonia, progressed to total/severe LSCD despite appropriate management
      including early amniotic membrane transplantation. The Dua classification
      includes conjunctival involvement, having a greater value in predicting the final
      clinical outcome when grading chemical eye injuries.

PMID- 30199399
TI  - Not Your Typical Dyspnea of Pregnancy: A Case Report of Transcatheter Valve-in
      Valve Replacement During Pregnancy.
AB  - Because technology for valvular replacement continues to evolve, we expect it to
      be further reaching in the applications for intermediate- to high-risk surgical
      candidates. Although the patient population for transcatheter aortic valve
      replacement has widened, it is still extremely rare in the pregnant patient. We
      report a case of a transcatheter valve-in-valve implantation in the second
      trimester of pregnancy. The patient experienced an excellent outcome after
      comprehensive coordination across multiple services. We discuss anesthetic
      considerations in the care of the pregnant patient for transcatheter aortic valve
      implantation.

PMID- 30199400
TI  - Hemodynamic Instability and Lipid Emulsion Resuscitation After Subcutaneous
      Injection of a Liposomal Bupivacaine Admixture: A Case Report.
AB  - This case report describes a patient whose blood pressure decreased from a
      systolic pressure of 130-140 to 70-80 mm Hg after receiving extended-release
      liposomal bupivacaine in combination with plain bupivacaine. An 83-year-old woman
      with hepatocellular carcinoma presented for right hepatectomy and
      cholecystectomy. No hemodynamic instability was noted during the procedure. When
      an admixture of liposomal bupivacaine and bupivacaine hydrochloride was
      infiltrated into the surgical incision site during skin closure, the patient then
      became profoundly hypotensive. Her blood pressure was supported with
      phenylephrine boluses and continuous phenylephrine infusion. Lipid emulsion
      therapy was given to treat suspected local anesthetic toxicity. In response, the
      patient's blood pressure recovered and the vasopressor requirement was
      significantly reduced.

PMID- 30199401
TI  - Radiofrequency Ablation of the Stellate Ganglion for Management of Acute Digital
      Ischemia: A Case Report.
AB  - The authors present a report of a pulsed radiofrequency ablation of the stellate
      ganglion performed on a patient with microemboli to the hand from a thrombosed
      abandoned arteriovenous fistula. The patient was initially managed using
      vasodilators and anticoagulation. However, the patient's skin mottling, pain, and
      decreased strength persisted. Ablation of the stellate ganglia increased
      perfusion to his hand and likely prevented amputation that has lasted for
      approximately 1 year. While radiofrequency ablation is more commonly used for
      pain syndromes, this is an example of its use in the treatment and potential
      treatment of acute ischemia.

PMID- 30199402
TI  - Best perioperative practice in management of ambulatory patients with obstructive
      sleep apnea.
AB  - PURPOSE OF REVIEW: The perioperative outcome in obstructive sleep apnea (OSA)
      patients undergoing ambulatory surgery can be potentially impacted by the type of
      anesthetic technique, fluid management and choice of anesthetic agents. This
      review highlights the best perioperative practices in the management of OSA
      patients undergoing ambulatory surgical procedures. RECENT FINDINGS: A recent
      meta-analysis found that STOP-Bang might be used as a perioperative risk
      stratification tool. Patients with high-risk OSA (STOP-Bang >=3) were found to be
      associated with an increased risk of postoperative complications and prolonged
      length of hospital stay compared with low-risk OSA (STOP-Bang 0-2) patients
      undergoing noncardiac surgical procedures. A bidirectional relationship exists
      between OSA and difficult airway. Both suspected or diagnosed OSA may be
      associated with either difficult intubation or difficult mask ventilation or
      both. A recent meta-analysis identified OSA as an important risk factor for
      opioid-induced respiratory depression. A dose-response relationship was shown
      between the morphine equivalent daily dose and death or near-death events in OSA
      patients undergoing surgery. Postoperative continuous monitoring is recommended
      for high-risk OSA patients receiving opioids. Minimising the dose of muscle
      relaxant, neuromuscular monitoring and ensuring complete reversal of
      neuromuscular blockade before extubation is essential in OSA patients to avoid
      postoperative complications. Whenever feasible, regional anesthesia with
      multimodal analgesia may be considered as a better alternative to general
      anesthesia in OSA patients. SUMMARY: Patients with OSA and associated
      comorbidities present a challenge to anesthesiologists as they are at a high risk
      of perioperative complications. It is important to identify patients with OSA,
      with the goal to raise awareness among providers, mitigate risk and improve
      outcomes.

PMID- 30199403
TI  - Mitochondrial disease genetics update: recent insights into the molecular
      diagnosis and expanding phenotype of primary mitochondrial disease.
AB  - PURPOSE OF REVIEW: Primary mitochondrial disease (PMD) is a genetically and
      phenotypically diverse group of inherited energy deficiency disorders caused by
      impaired mitochondrial oxidative phosphorylation (OXPHOS) capacity. Mutations in
      more than 350 genes in both mitochondrial and nuclear genomes are now recognized
      to cause primary mitochondrial disease following every inheritance pattern. Next
      generation sequencing technologies have dramatically accelerated mitochondrial
      disease gene discovery and diagnostic yield. Here, we provide an up-to-date
      review of recently identified, novel mitochondrial disease genes and/or
      pathogenic variants that directly impair mitochondrial structure, dynamics,
      and/or function. RECENT FINDINGS: A review of PubMed publications was performed
      from the past 12 months that identified 16 new PMD genes and/or pathogenic
      variants, and recognition of expanded phenotypes for a wide variety of
      mitochondrial disease genes. SUMMARY: Broad-based exome sequencing has become the
      standard first-line diagnostic approach for PMD. This has facilitated more rapid
      and accurate disease identification, and greatly expanded understanding of the
      wide spectrum of potential clinical phenotypes. A comprehensive dual-genome
      sequencing approach to PMD diagnosis continues to improve diagnostic yield,
      advance understanding of mitochondrial physiology, and provide strong potential
      to develop precision therapeutics targeted to diverse aspects of mitochondrial
      disease pathophysiology.

PMID- 30199404
TI  - Challenges and opportunities for effective delivery of clinical genetic services
      in the U.S. healthcare system.
AB  - PURPOSE OF REVIEW: Demand for clinical genetics and genomics services is
      increasing. As discussed in this study, the clinical genetics and genomics
      workforce is small. How to meet the demand with a limited workforce requires
      innovation. RECENT FINDINGS: Background data regarding the current state of
      clinical genetic services including volume of services and make-up of the
      clinical genetics workforce are presented. The study then identifies
      opportunities to increase access to clinical genetic service providers using new
      models of service and discusses examples of solutions which have been implemented
      in some practice settings. Creative uses of technology to increase providers'
      efficiency are highlighted. SUMMARY: Clinical genetics service providers need to
      rise to the occasion and lead the transformation of clinical genetic service
      delivery. Many of the examples of solutions described in the study can be
      implemented by other providers now. Additionally, the described solutions may
      serve to inspire genetic providers to create their own new solutions, which
      should then be shared with the provider community.

PMID- 30199405
TI  - Headache disorders: an update.

PMID- 30199406
TI  - Sleep and asthma.
AB  - PURPOSE OF REVIEW: There is a longstanding recognition of the detrimental effect
      of poorly controlled asthma on sleep, but recent years have seen a growing
      interest in how asthma and sleep may interact. This review examines the current
      evidence of relationships between asthma, sleep and sleep disorders. RECENT
      FINDINGS: Poor quality sleep and sleep disturbance is highly prevalent in
      asthmatic patients, and particularly in those with severe asthma. Impaired sleep
      quality correlates with worse asthma control and quality of life. Sleep
      disturbance in asthma may be related to due circadian variation in airway
      inflammation, but may also be related to specific sleep disorders. Obstructive
      sleep apnoea (OSA) appears to be significantly more common in asthmatic patients
      than nonasthmatic patients, and treatment of OSA with continuous positive airway
      pressure (CPAP) may lead to improved asthma-specific quality of life. Nocturnal
      CPAP may also be of benefit to asthmatic patients without OSA, potentially
      because of stretching of airway smooth muscle. Insomnia is also highly prevalent
      in severe asthma patients, and is associated with a history of poor asthma
      control and increased healthcare utilization. SUMMARY: Asthma, sleep and sleep
      disorders appear to have complex, but significant relationships. Prospective
      observational and controlled interventional studies are needed to quantify how
      addressing sleep difficulties may benefit asthma patients.

PMID- 30199407
TI  - Key aspects of PCSK9 inhibition beyond LDL lowering.
AB  - PURPOSE OF REVIEW: Our primary objective is to review the most recent findings on
      the biology of PCSK9 and on two key aspects of PCSK9 inhibition beyond LDL
      control of great clinical relevance: the regulation of lipoprotein (a)
      circulating levels by PCSK9 inhibitors and the putative diabetogenic effects of
      these novel therapies. RECENT FINDINGS: The reality of two distinct extracellular
      and intracellular pathways by which PCSK9 decreases the abundance of the LDLR at
      the surface of many cell types, most importantly hepatocytes, has recently been
      established. In contrast, the exact mechanisms by which PCSK9 inhibitors lower
      the circulating levels of lipoprotein (a) remain a point of major dispute.
      Despite strong indications from genetic studies that PCSK9 inhibition should
      increase diabetes risk, no such effect has been observed in clinical trials, and
      in-vitro and in-vivo studies do not clarify this issue. SUMMARY: The trafficking
      pathways by which PCSK9 enhance LDLR degradation via the endolysosomal
      extracellular route or via the Golgi-lysosomal intracellular route remain to be
      fully elucidated. The mechanisms by which PCSK9 inhibitors reduce lipoprotein (a)
      also merit additional research efforts. The role of PCSK9 on glucose metabolism
      should likewise be studied in depth.

PMID- 30199408
TI  - Gastroduodenal motility disorders.
AB  - PURPOSE OF REVIEW: This review summarizes recent progress in the epidemiology,
      pathophysiology and treatment of gastroduodenal motility disorders with an
      emphasis on functional dyspepsia and gastroparesis. RECENT FINDINGS:
      Pathophysiological research has focused on the association of delayed emptying
      and impaired accommodation with symptom pattern. Studies also confirmed the
      presence of altered mucosal integrity and low-grade immune activation in the
      duodenum in functional dyspepsia, while changes in numbers of interstitial cells
      of Cajal and myenteric neurons were confirmed in gastroparesis. Treatment
      advances in gastroparesis include new prokinetics such as the ghrelin receptor
      agonist relamorelin and the antiemetic agent aprepitant. The efficacy and use of
      neuromodulators were reviewed and new management guidelines for functional
      dyspepsia were published. SUMMARY: Pathophysiological research has focused on
      cellular changes in gastroparesis and gastroduodenal motility disorders. New
      treatments include relamorelin and aprepitant for gastroparesis.

PMID- 30199410
TI  - The American Organization of Nurse Executives and American Hospital Association
      Initiatives Work to Combat Violence.

PMID- 30199411
TI  - Nurse Managers Speak Out About Disruptive Nurse-to-Nurse Relationships.

PMID- 30199409
TI  - Surgical Treatment of Subfibular Ossicle in Children: A Retrospective Study of 36
      Patients with Functional Instability.
AB  - BACKGROUNDS: To evaluate the surgical management of a symptomatic subfibular
      ossicle after severe ankle sprain with functional instability and pain sequelae
      in children. METHODS: We analyzed 36 patients complaining of functional
      instability without laxity, 1 year after an ankle inversion trauma associated
      with the observation of a subfibular ossicle. We systematically suggested the
      open excision of the residual ossicles, followed by 6 weeks of immobilization and
      proprioceptive physiotherapy. Seventeen of them, constituting the "resection"
      group accepted this surgical approach. The remaining 19 patients, the "control"
      group, received only rehabilitative care. The American Orthopaedic Foot and Ankle
      Society ankle pain and function score was evaluated in both groups. RESULTS: The
      mean latest follow-up was 4 years and 4 months (range, 1 y 8 mo to 14 y 7 mo). A
      significant improvement of the American Orthopaedic Foot and Ankle Society score
      was observed and was significantly higher in the resection group with a mean gain
      of 31 points (SD=31.8), versus 7 points (SD=7) in the control group (P<0.001).
      CONCLUSIONS: We conclude that in the absence of objective laxity, excision of the
      os subfibulare appears as a simple and effective technique in the treatment of
      posttraumatic functional instability and ankle pain. LEVEL OF EVIDENCE: Level IV
      retrospective case-control study.

PMID- 30199412
TI  - Observational Surveillance Approach to Detect Novel Work-Related Diseases and
      Hazards: An Application to a Belgian Occupational Health and Safety Database.
AB  - OBJECTIVES: Rapid changes in working conditions give rise to new occupational
      health risks. We applied the Spectrosome approach, a network-based analysis, to
      investigate associations between disease and multiple occupational exposures.
      METHODS: We investigated work and health's associations in a specific sector: the
      agricultural sector and for a specific and frequent health complaint: sore
      throat; using PRECUBE dataset of the Belgian Occupational Health and Safety,
      containing 381.615 occupational health observations. We compared the results of
      the spectrosome with classic frequency analyses. RESULTS: Spectrosome approach
      reports more significant signals of multiple associations of agents compare to
      the frequency analysis. CONCLUSION: This difference justifies the usefulness of
      taking into account the multiplicity of causes leading to a health event, which
      is a clear asset of the Spectrosome method.

PMID- 30199413
TI  - Process Evaluation of a Digital Platform-Based Implementation Strategy Aimed at
      Work Stress Prevention in a Health Care Organization.
AB  - OBJECTIVE: The objective was to evaluate the process and feasibility of a digital
      platform-based implementation strategy aimed at work stress prevention. METHODS:
      The process evaluation was performed alongside a controlled trial within a health
      care organization, in the experimental group (N = 221). Mental models, context,
      and barriers and facilitators were measured. In addition, dose delivered, reach,
      and dose received were assessed. RESULTS: Employees reported relatively high
      readiness for change. Personnel shortage and a recent restructuring of the
      organization hindered use of the strategy. Low management support and high
      turnover stagnated strategy deployment. Dose delivered was 13/15, reach was
      11/15, and dose received was 5/15. CONCLUSIONS: Strategy implementation was
      moderately successful, as sustained strategy use by the teams appeared to be a
      challenge. The strategy can be feasible with sufficient management support and
      resources.

PMID- 30199414
TI  - Unexpected higher blood loss associated with higher dose epsilon-aminocaproic
      acid in pediatric scoliosis surgery.
AB  - The purpose of this study was to determine if a higher dosing of epsilon
      aminocaproic acid (EACA) is associated with less perioperative blood loss than a
      lower dose. A total of 74 patients having scoliosis surgery were analyzed. Of the
      74 patients, 36 patients received EACA (10 mg/kg/h) and 38 patients received EACA
      (33 mg/kg/h). After controlling for key variables, an infusion of 33 mg/kg/h of
      EACA was associated with an increase in intraoperative blood loss of 8.1 ml/kg
      compared with an infusion of 10 mg/kg/h of EACA. A 33 mg/kg/h intraoperative
      infusion is associated with higher intraoperative blood loss than an infusion at
      10 mg/kg/h.

PMID- 30199415
TI  - Simultaneous treatment for patellar instability and genu valgum in skeletally
      immature patients: a preliminary study.
AB  - Genu valgum is a risk factor for patellar instability. The study purpose was to
      report on preliminary results of medial patellofemoral ligament (MPFL)
      reconstruction and simultaneous growth modulation, in patients with patellar
      instability and genu valgum. A total of seven patients (eight knees) with MPFL
      reconstruction and medial transphyseal screw insertion for genu valgum correction
      were assessed using full-length radiographs. Genu valgum corrected from 13.1
      degrees  to 3.7 degrees  at mean 11.7 months, without compromising patellar
      stability. One patient each had 6 degrees  overcorrection and 5 degrees  rebound
      valgus. Guided growth using transphyseal screw during MPFL reconstruction could
      achieve deformity correction without interference with MPFL graft placement.

PMID- 30199417
TI  - Evaluation of an AI-Based Detection Software for Acute Findings in Abdominal
      Computed Tomography Scans: Toward an Automated Work List Prioritization of
      Routine CT Examinations.
AB  - OBJECTIVE: The aim of this study was to test the diagnostic performance of a deep
      learning-based triage system for the detection of acute findings in abdominal
      computed tomography (CT) examinations. MATERIALS AND METHODS: Using a RIS/PACS
      (Radiology Information System/Picture Archiving and Communication System) search
      engine, we obtained 100 consecutive abdominal CTs with at least one of the
      following findings: free-gas, free-fluid, or fat-stranding and 100 control cases
      with absence of these findings. The CT data were analyzed using a convolutional
      neural network algorithm previously trained for detection of these findings on an
      independent sample. The validation of the results was performed on a Web-based
      feedback system by a radiologist with 1 year of experience in abdominal imaging
      without prior knowledge of image findings through both visual confirmation and
      comparison with the clinically approved, written report as the standard of
      reference. All cases were included in the final analysis, except those in which
      the whole dataset could not be processed by the detection software. Measures of
      diagnostic accuracy were then calculated. RESULTS: A total of 194 cases were
      included in the analysis, 6 excluded because of technical problems during the
      extraction of the DICOM datasets from the local PACS. Overall, the algorithm
      achieved a 93% sensitivity (91/98, 7 false-negative) and 97% specificity (93/96,
      3 false-positive) in the detection of acute abdominal findings. Intra-abdominal
      free gas was detected with a 92% sensitivity (54/59) and 93% specificity (39/42),
      free fluid with a 85% sensitivity (68/80) and 95% specificity (20/21), and fat
      stranding with a 81% sensitivity (42/50) and 98% specificity (48/49). False
      positive results were due to streak artifacts, partial volume effects, and a
      misidentification of a diverticulum (each n = 1). CONCLUSIONS: The algorithm's
      autonomous detection of acute pathological abdominal findings demonstrated a high
      diagnostic performance, enabling guidance of the radiology workflow toward
      prioritization of abdominal CT examinations with acute conditions.

PMID- 30199418
TI  - Caseous Calcification of the Mitral Annulus: Mimic and Malady.

PMID- 30199419
TI  - Differences of Recovery from Rocuronium-induced Deep Paralysis in Response to
      Small Doses of Sugammadex between Elderly and Nonelderly Patients.
AB  - WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW:
      BACKGROUND:: Complete recovery from rocuronium-induced muscle paralysis with
      sugammadex is reported to be delayed in elderly patients. The authors tested a
      hypothesis that recovery from deep neuromuscular block with low-dose sugammadex
      is slower (primary hypothesis) and incidence of recurarization is higher
      (secondary hypothesis) in elderly patients than in nonelderly patients. METHODS:
      In anesthetized elderly (n = 20; 76.9 +/- 5.0 yr of age) and nonelderly patients
      (n = 20; 53.7 +/- 12.8 yr of age) under deep paralysis with rocuronium, change of
      train-of-four ratio per minute (primary outcome variable) was measured with an
      acceleromyograph neuromuscular monitor during spontaneous recovery from
      rocuronium-induced muscle paralysis (0.6 mg/kg) and after infusion of low-dose
      sugammadex (50 ug . kg . min). Recurarization was defined as the negative change
      of train-of-four ratio. RESULTS: Spontaneous train-of-four ratio recovery rate
      was significantly slower in the elderly group (median [25th percentile, 75th
      percentile]: 1.89 [1.22, 2.90] %/min) than in the nonelderly group (3.45 [1.96,
      4.25] %/min, P = 0.024). Train-of-four ratio change rate in response to low-dose
      sugammadex was significantly slower in elderly (0.55 [-0.29, 1.54] %/min) than in
      the nonelderly group (1.68 [0.73, 3.13] %/min, P = 0.024). Incidence of
      recurarization was significantly higher in the elderly group than in the
      nonelderly group (35% vs. 5%, P = 0.044). Multiple linear regression analyses
      indicate that slower spontaneous train-of-four ratio recovery rate and impaired
      renal function are two major contributing factors that decrease train-of-four
      ratio change rate in response to low-dose sugammadex. CONCLUSIONS: Elderly
      patients are at greater risk for recurarization and residual muscle paralysis
      when low-dose sugammadex is administered.

PMID- 30199416
TI  - Traffic-related Air Pollution and Pregnancy Loss.
AB  - BACKGROUND: Traffic-related air pollution has been linked to multiple adverse
      pregnancy outcomes. However, few studies have examined pregnancy loss, targeting
      losses identified by hospital records, a large limitation as it does not capture
      events not reported to the medical system. METHODS: We used a novel variation of
      the time-series design to determine the association, and identify the critical
      window of vulnerability, between week-to-week traffic-related air pollution and
      conceptions resulting in live births, using nitrogen dioxide (NO2) as a traffic
      emissions tracer. We used information from all live births recorded at Beth
      Israel Deaconess Medical Center in Boston, MA (2000-2013) and all live births in
      Tel Aviv District, Israel (2010-2013). RESULTS: In Boston (68,969 live births),
      the strongest association was during the 15th week of gestation; for every 10 ppb
      of NO2 increase during that week, we observed a lower rate of live births (rate
      ratio [RR] = 0.87; 95% confidence interval [CI], 0.78, 0.97), using live birth
      identified conceptions to infer pregnancy losses. In the Tel Aviv District
      (95,053 live births), the strongest estimate was during the 16th gestational week
      gestation (RR = 0.82; 95% CI, 0.76, 0.90 per 10 ppb of NO2). CONCLUSIONS: Using
      weekly conceptions ending in live birth rather than identified pregnancy losses,
      we comprehensively analyzed the relationship between air pollution and all
      pregnancy loss throughout gestation. The observed results, with remarkable
      similarity in two independent locations, suggest that higher traffic-related air
      pollution levels are associated with pregnancy loss, with strongest estimates
      between the 10th and 20th gestational weeks.

PMID- 30199420
TI  - Brain Dynamics and Temporal Summation of Pain Predicts Neuropathic Pain Relief
      from Ketamine Infusion.
AB  - WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW:
      BACKGROUND:: Ketamine is an N-methyl-D-aspartate receptor antagonist that reduces
      temporal summation of pain and modulates antinociception. Ketamine infusions can
      produce significant relief of neuropathic pain, but the treatment is resource
      intensive and can be associated with adverse effects. Thus, it is crucial to
      select patients who might benefit from this treatment. The authors tested the
      hypothesis that patients with enhanced temporal summation of pain and the
      capacity to modulate pain via the descending antinociceptive brain pathway are
      predisposed to obtain pain relief from ketamine. METHODS: Patients with
      refractory neuropathic pain (n = 30) and healthy controls underwent quantitative
      sensory testing and resting-state functional magnetic resonance imaging and then
      completed validated questionnaires. Patients then received outpatient intravenous
      ketamine (0.5 to 2 mg . kg . h; mean dose 1.1 mg . kg . h) for 6 h/day for 5
      consecutive days. Pain was assessed 1 month later. Treatment response was defined
      as greater than or equal to 30% pain relief (i.e., reduction in pain scores). We
      determined the relationship between our primary outcome measure of pain relief
      with pretreatment temporal summation of pain and with brain imaging measures of
      dynamic functional connectivity between the default mode network and the
      descending antinociceptive brain pathway. RESULTS: Approximately 50% of patients
      achieved pain relief (mean +/- SD; Responders, 61 +/- 35%; Nonresponders, 7 +/-
      14%). Pretreatment temporal summation was associated with the effect of ketamine
      (rho = -0.52, P = 0.003) and was significantly higher in Responders (median
      [25th, 75th] = 200 [100, 345]) compared with Nonresponders (44 [9, 92]; P =
      0.001). Pretreatment dynamic connectivity was also associated with the clinical
      effect of ketamine (rho = 0.51, P = 0.004) and was significantly higher in
      Responders (mean +/- SD, 0.55 +/- 0.05) compared with Nonresponders (0.51 +/-
      0.03; P = 0.006). Finally, the dynamic engagement of the descending
      antinociceptive system significantly mediated the relationship between
      pretreatment pain facilitation and pain relief (95% CI, 0.005 to 0.065).
      CONCLUSIONS: These findings suggest that brain and behavioral measures have the
      potential to prognosticate and develop ketamine-based personalized pain therapy.

PMID- 30199423
TI  - Sodium Hyaluronate and Platelet-Rich Plasma for Partial-Thickness Rotator Cuff
      Tears.
AB  - PURPOSE: Treatment of partial-thickness rotator cuff tears (PTRCTs) remains
      controversial. Few studies have focused on the conservative and new measurements
      of small to medium PTRCTs. The use of sodium hyaluronate (SH) or platelet-rich
      plasma (PRP) as a method for rotator cuff repair requires further investigation.
      The aim of this study was to evaluate the combined use of SH and PRP in the
      treatment of small to medium PTRCTs.Study designDouble-blinded randomized trial.
      METHODS: Individuals with PTRCTs detected by clinical examination and magnetic
      resonance imaging (MRI) were included in this study. The patients were randomly
      assigned to receive subacromial injections of normal saline (NS), SH, PRP or
      SH+PRP once a week for four weeks. The primary outcome measure was the Constant
      score, and the secondary outcomes included the American shoulder and elbow
      surgeons (ASES) and visual analog scale (VAS) scores. All of the clinical
      outcomes were assessed at pretreatment and 1, 3, 6, and 12 months posttreatment.
      MRI was used to evaluate the evolution of the cuff defect after 1 year. RESULTS:
      PRP group and SH+PRP group showed a significantly higher Constant score and ASES
      score after the treatments. There were significant differences between the SH+PRP
      group and SH or PRP group at 12 months in the Constant, VAS and ASES scores. MRI
      results showed that the tear size significantly decreased in both the PRP and
      SH+PRP groups, especially in the SH+PRP group. CONCLUSION: Our study provided
      evidence of the efficacy of PRP injection in the healing of small to medium
      PTRCTs. Moreover, the combined injection of SH and PRP yielded a better clinical
      outcome than SH or PRP alone.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- 30199421
TI  - Comparative Evaluation of Recombinant Human Bone Morphogenetic Protein
      2/Hydroxyapatite and Bovine Bone for New Bone Formation in Alveolar Ridge
      Preservation.
AB  - PURPOSE: Hydroxyapatite treated with recombinant human bone morphogenetic protein
      2/Hydroxyapatite (rhBMP-2/HA) or bovine bone was applied on extraction sockets
      for alveolar ridge preservation, and the results were compared with respect to
      clinical and histological bone formation. MATERIALS AND METHODS: This was a
      prospective, randomized controlled clinical trial performed on 20 implant
      placement sites (10 in the experimental and 10 in the control group). rhBMP-2/HA
      was applied on extraction sockets in the experimental group and bovine bone on
      those of the control group. The bone at the corresponding sites was biopsied 3
      months later, and clinical, histological, and histomorphometric analyses were
      performed. RESULTS: The alveolar bone height was well preserved in both groups
      with relatively less change in width in the experimental group compared with the
      control group. The percentage of new bone was 25.37% +/- 17.23% in the
      experimental group and 6.13% +/- 4.32% in the control group; the difference was
      statistically significant. CONCLUSIONS: The alveolar ridge was preserved
      clinically and histologically in both groups. rhBMP-2/HA resulted in greater new
      bone formation than bovine bone 3 months after the surgery.

PMID- 30199424
TI  - Efficacy of Contact Lens Care Solutions in Removing Cholesterol Deposits From
      Silicone Hydrogel Contact Lenses.
AB  - PURPOSE: To determine the efficacy of multipurpose solutions (MPSs) on the
      removal of cholesterol deposits from silicone hydrogel (SH) contact lens
      materials using an in vitro model. MATERIALS AND METHODS: Five SH lens materials:
      senofilcon A, comfilcon A, balafilcon A, lotrafilcon A, and lotrafilcon B were
      removed from the blister pack (n=4 for each lens type), incubated for 7 days at
      37 degrees C in an artificial tear solution containing C radiolabeled
      cholesterol. Thereafter, lenses were stored in a preserved saline solution
      control (Sensitive Eyes Saline Plus) or cleaned with 1 of the 5 MPSs
      incorporating different preservatives (POLYQUAD/ALDOX, polyquaternium
      1/alexidine, polyquaternium-1/PHMB, and 2 based on PHMB alone) using a rub and
      rinse technique, according to the manufacturer's recommendations, and stored in
      the MPS for a minimum of 6 hr. Lenses were then extracted with 2:1
      chloroform:methanol, analyzed in a beta counter, and MUg/lens of cholesterol was
      determined. RESULTS: Balafilcon A and senofilcon A lens materials showed the
      highest amounts of accumulated cholesterol (0.93+/-0.02 MUg/lens; 0.95+/-0.01
      MUg/lens, respectively), whereas lotrafilcon A and lotrafilcon B deposited the
      lowest amounts (0.37+/-0.03 MUg/lens; 0.47+/-0.12 MUg/lens, respectively). For
      all lens materials, the MPS preserved with POLYQUAD/ALDOX removed more deposited
      cholesterol than any other test solution; however, the amount of removed
      cholesterol contamination from the individual contact lenses was only
      statistically significant for balafilcon A and senofilcon A (P=0.006 and P=0.042,
      respectively). Sensitive eyes and the other evaluated MPSs showed no significant
      effect on cholesterol removal (P>0.05). CONCLUSION: Cholesterol-removal efficacy
      varies depending on the combination of lens material and solution. Only 1 MPS
      showed a statistically significant reduction of cholesterol deposit for only 2 of
      the 5 tested lens materials.

PMID- 30199425
TI  - Ocular Surface Disease and Glaucoma Medications: A Clinical Approach.
AB  - OBJECTIVES: Ocular surface disease frequently coexists with glaucoma and may be
      initiated or exacerbated by topical glaucoma medications. We performed a review
      of current literature to assess the prevalence, causes, and treatment of ocular
      surface disease in glaucoma patients, specifically those on topical therapy.
      METHODS: A Pubmed database search was conducted. A total of 720 articles
      published from 1972 to 2018 were found in relation with ocular surface disease,
      glaucoma, and glaucoma medications. Of these, 102 articles were included in this
      analysis. We included primary and empirical studies for patients on topical
      glaucoma medications. Exclusion criteria included case reports, non-English
      studies, and articles unrelated to the primary subject of this review. RESULTS:
      Ocular surface disease among normal and glaucomatous eyes was evaluated based on
      diagnostic testing including clinical examination and questionnaires to determine
      visual function and quality of life. Glaucoma medications can be associated with
      toxicities to the ocular surface, most often due to the nature of the
      preservative included in the medication; however, the incidence of toxicity can
      be mitigated by the use of preservative free medications, decreased preservative
      medications, or treatment of dry eye disease. Treatment of glaucoma with laser
      trabeculoplasty or minimally invasive glaucoma surgeries that spare the
      conjunctiva and the cornea may avoid or decrease reliance on topical glaucoma
      medications, potentially avoiding the initiation or progression of ocular surface
      disease. CONCLUSIONS: Recognition and treatment of ocular surface disease in
      glaucoma patients may improve patient quality of life and medication adherence.
      This may ultimately improve glaucoma treatment outcomes.

PMID- 30199426
TI  - Homeless No More: A Christ-Centered, Comprehensive Homeless Recovery Program.
AB  - Caring for vulnerable and marginalized populations is a central tenet of
      professional nursing, and of Christian service. Due to the scope and complexities
      of problems associated with homelessness, nurses may feel overwhelmed and ill
      equipped to serve homeless individuals. Strategies for ending homelessness
      largely include resource-intensive, publicly supported housing and comprehensive
      physical and mental health services. The role of spirituality in recovery from
      homelessness has not been widely examined. This article describes one homeless
      shelter's successful Christ-centered, comprehensive approach to helping
      individuals recover from homelessness. The integral role of the nurse in the
      multidisciplinary team and practical nursing interventions are described.

PMID- 30199427
TI  - Medication Treatment With Methadone or Buprenorphine: Differential Reasons for
      Premature Discharge.
AB  - OBJECTIVES: Medication treatment with methadone or buprenorphine has shown
      demonstrated effectiveness for opioid dependence; while premature discharge is
      associated with adverse outcomes. Specific reasons for premature discharge
      generally fall into 2 broad categories (ie, patient- and program-initiated).
      Previous studies have typically failed to distinguish between different types of
      discharge reasons among patients who leave treatment early. This study sought to
      determine whether type of medication was associated with differential discharge
      reasons among medication treatment patients who were prematurely discharged.
      METHODS: Data were derived from electronic health records for 5486 patients
      prematurely discharged from 41 for-profit licensed opioid treatment programs in
      the United States from 2012 to 2013. All patients were treated with methadone or
      buprenorphine. Patients were studied through retrospective chart review until
      premature discharge. RESULTS: Buprenorphine patients who left treatment
      prematurely were 2.18 times (95% confidence interval [CI] 1.89-2.53) more likely
      to be discharged against medical advice relative to methadone patients after
      controlling for intake differences. Methadone patients were 1.76 times (95% CI
      1.47-2.10) more likely to be administratively discharged after adjustment for
      covariates. CONCLUSIONS: Further research is warranted to determine whether
      individually-tailored strategies may improve retention for certain patients based
      on medication. Ongoing review of program rules and policies may benefit methadone
      patients, who are nearly twice as likely to be discharged for an administrative,
      program-initiated reason. Strategies including contingency management,
      motivational incentives, and psychoeducation regarding the advantages of
      retention may benefit buprenorphine patients who are over 2 times more likely to
      leave treatment early due to a patient-initiated reason.

PMID- 30199429
TI  - Repair of a Large Defect Involving the Nose, Cheek, and Upper Cutaneous Lip.

PMID- 30199428
TI  - Increased Cancer Screening for Low-income Adults Under the Affordable Care Act
      Medicaid Expansion.
AB  - BACKGROUND: We tested whether Medicaid expansion under the Affordable care Act
      was associated with increased screening for cervical, breast, and colorectal
      cancer among low-income adults. METHODS: We analyzed Behavioral Risk Factor
      Surveillance System data, identifying 2012 as preexpansion and 2016 as
      postexpansion (2014 was treated as a wash-out, and 2013 and 2015 had missing
      screening data from most states). States (including District of Columbia) either
      expanded Medicaid in 2014 (n=28) or not (n=18); five states that expanded after
      2014 were excluded. Participants included low-income adults aged 18-64 without
      dependent children. A difference-in-difference approach tested whether expansion
      was significantly associated with screening, controlling for time, state effects,
      age, sex, race/ethnicity, education, and urban/rural population. For comparison,
      we also conducted analyses among the low-income Medicare (aged 65 and above)
      population, and a higher income population. RESULTS: There was a significant
      expansion effect for women aged 18-64 for cervical cancer screening (N=29,059;
      odds ratio, 1.04; 95% confidence interval, 1.01-1.08), and for adults 50-64 for
      colorectal cancer screening (N=32,290; odds ratio, 1.12; 95% confidence interval,
      1.03-1.22). Effects for mammography for women aged 40-64, or aged 50-64, were not
      significant. As expected, there were no significant improvements associated with
      expansion among the Medicare population, or among a population ineligible due to
      higher income. CONCLUSIONS: Medicaid expansion under the Affordable Care Act was
      associated with increased screening for cervical and colorectal cancer for low
      income adults. It will be important to monitor possible adverse cancer outcomes
      in nonexpansion states among vulnerable populations over time.

PMID- 30199430
TI  - Outcomes for Invasive Melanomas Treated With Mohs Micrographic Surgery: A
      Retrospective Cohort Study.
AB  - BACKGROUND: Mohs micrographic surgery (MMS) has been used effectively to treat
      invasive melanoma. OBJECTIVE: To further study the safety and efficacy of MMS in
      the treatment of invasive melanoma. METHODS AND MATERIALS: A retrospective cohort
      study evaluated 123 melanomas excised using MMS with MART-1 immunostain. Local
      recurrence, metastasis, overall survival, and disease-free survival rates were
      calculated. These were compared with historical controls. RESULTS: Among included
      patients, 78 were men (63%) and 45 were women (37%), with a mean age of 66.48
      years. Mean follow-up time was 1,273 days (3.49 years). Local recurrence was
      identified in 2/123 (1.63%; 95% confidence interval, 0.20%-5.75%) lesions. Local
      recurrence was identified in 1/70 (1.43%; 95% confidence interval, 0.04%-7.70%)
      of head and neck cases. Tumor location was head and neck in 70 lesions (56.9%).
      Overall survival was 95.12% and disease-specific survival was 100%. CONCLUSION:
      Mohs micrographic surgery is an effective treatment method for invasive melanoma,
      as evidenced by low recurrence rates and high rates of disease-free survival.

PMID- 30199431
TI  - Endogenous Peroxidase Activity on Mohs Frozen Sections.

PMID- 30199432
TI  - Dual-Plane Undermining and Galeal Stitch for Dermal Tension Relief in High
      Tension Defects, Hemostats for High-Tension Knot Placement, and Debeveling for
      Exact Dermal Approximation: A Video Walk-Through.

PMID- 30199433
TI  - Micrographic Surgery and Dermatologic Oncology Fellowship Selection Criteria.
AB  - BACKGROUND: Obtaining a fellowship position for Micrographic Surgery and
      Dermatologic Oncology (MSDO) is becoming very competitive. Applicant qualities
      desired by MSDO fellowship directors have not been previously explored in a
      systematic way. OBJECTIVE: To characterize the prevailing practices of selecting
      MSDO fellows. METHODS AND MATERIALS: Cross-sectional study based on an anonymous
      online survey of MSDO fellowship directors. RESULTS: There were 34 completed
      surveys. Selection criteria with the highest importance to fellowship directors
      were the ability to work well and get along with others, interview, work ethic,
      and letter of recommendation from the Mohs micrographic surgery director at the
      applicant's residency. The criteria with the lowest importance were advanced
      degrees, medical licensing examination scores, and membership in Alpha Omega
      Alpha. Specific applicant factors that were looked upon most positively by
      fellowship directors include applicant from own institution and applicant's
      personal reasons and circumstances, whereas factors that were most unfavorable
      include applicant's desire to practice in the same city/area as the fellowship
      location and graduate of foreign medical school. CONCLUSION: Although variations
      existed, MSDO fellowship directors collectively placed greater importance on
      criteria that reflect interpersonal skills than on objective measures of academic
      performance, which highlights the importance of "fit."

PMID- 30199434
TI  - Reply to Commentary on Impact of National Comprehensive Cancer Network Guidelines
      on Case Selection and Outcomes for Sentinel Lymph Node Biopsy in Thin Melanoma.

PMID- 30199435
TI  - A Wrong-Site Surgery Protocol for Dermatological Surgery.

PMID- 30199436
TI  - Erosive Pustular Dermatosis of the Scalp Treated With Aminolevulinic Acid
      Photodynamic Therapy and Postprocedure Silicone Gel.

PMID- 30199437
TI  - Intralesional Corticosteroid-Induced Perilesional and Perilymphatic Linear
      Hypopigmentation Successfully Treated With a 308-nm Excimer Light.

PMID- 30199438
TI  - Trends in Medicare Billing Among Mohs Surgeons in the United States During 2012:
      A Retrospective Cohort Study.
AB  - BACKGROUND: It is important to understand variability in practice patterns of
      Mohs surgeons. OBJECTIVE: To examine the practice patterns of physicians
      performing Mohs micrographic surgery (MMS) in the United States. METHODS AND
      MATERIALS: This retrospective cohort study of the 2012 Medicare Physician and
      Other Supplier Public Use Files includes all physicians who billed Medicare for
      MMS. RESULTS: The authors found 2,067 physicians who billed Medicare for MMS in
      2012. American College of Mohs Surgery (ACMS) members took a significantly higher
      average number of head and neck (H&N) and trunk layers compared with American
      Society for Mohs Surgery (ASMS) members and those with no membership (p < .001).
      Male surgeons, surgeons with more experience (21+ years out), surgeons in private
      practice, and those practicing in rural populations closed a significantly
      greater proportion of cases with flaps or grafts, as compared to females (p <
      .001), those with less experience (<21 years out) (p < .001), surgeons in
      academic practice (p = .004), and those practicing in urban or cluster
      populations (p < .001), respectively. CONCLUSION: There is significant
      variability in practices of Mohs surgeons in the United States.

PMID- 30199439
TI  - Repair of a Deep Defect on the Proximal Phalanx.

PMID- 30199440
TI  - Altered whole-brain gray matter volume in primary angle closure glaucoma
      patients: a voxel-based morphometry study.
AB  - The study aimed to compare the whole-brain gray matter volume (GMV) and white
      matter volume (WMV) difference between primary angle closure glaucoma (PACG)
      patients and health controls (HCs) using a voxel-based morphometry method. A
      total of 27 patients with PACG (17 males and 10 females) and 27 HCs (17 males and
      10 females), closely matched for age and education, were enrolled in the study.
      All subjects underwent magnetic resonance imaging (MRI) scans. The MRI data were
      processed using SPM8 software in voxel-based morphometry 8 toolbox. The
      relationship between the mean GMV values of brain regions and the clinical
      features including psychological testing and mean retinal nerve fiber layer
      (RNFL) thickness in PACG groups were analyzed by using Pearson correlation.
      Compared with HCs, PACG patients showed significantly decreased GMV values in the
      left cerebellum posterior lobe (CPL), right extra-nuclear, and right superior
      temporal gyrus. In contrast, PACG patients showed significantly increased GMV
      values in the left CPL, right CPL, right superior temporal gyrus, right thalamus
      and right insula (P<0.01). Moreover, in the PACG group, the left mean RNFL showed
      a positive correlation with the mean GMV values of the left CPL (r=0.719;
      P<0.001) and the right mean RNFL showed a positive correlation with the mean GMV
      values of the left CPL (r=0.721; P<0.001). The Hamilton depression score showed a
      positive correlation with the mean GMV values of right insula (r=0.897; P<0.001).
      Our results demonstrated that PACG patients showed altered brain structure in
      various regions related to visuomotor function, thalamocortical pathway, and
      emotion function, which might provide a useful informations to understanding the
      anatomy neural mechanisms of deficit in vision loss and depression in PACG.

PMID- 30199442
TI  - In the Next Issue.

PMID- 30199441
TI  - Fear conditioning downregulates miR-138 expression in the hippocampus to
      facilitate the formation of fear memory.
AB  - Fear memory is important for the survival of animals and is associated with
      certain anxiety disorders, such as posttraumatic stress disorder. A thorough
      understanding of the molecular mechanisms of fear memory, especially associative
      fear memory, is imperative. MicroRNA-138 (miR-138) is a widely distributed
      microRNA in the brain and is locally enriched at synaptic sites. The role of miR
      138 in the formation of fear memory is still largely unknown. In this study, a
      contextual fear conditioning (CFC) paradigm, bioinformatic methods, a luciferase
      assay, real-time PCR and western blot were used to evaluate the detailed effects
      of miR-138 on fear memory. We found that miR-138 transiently decreased in the
      dorsal hippocampus (DH) after CFC training. Upregulation or downregulation of miR
      138 in the DH with miR-138 agomir or antagomir treatment significantly impaired
      or enhanced the formation of CFC memory, respectively. Moreover, the effects of
      miR-138 in the DH on the formation of CFC memory were achieved by changing the
      expression of the downstream target gene calpain 1 (Capn1). Taken together, both
      the in-vitro evidence and the in-vivo evidence presented in this study support
      the involvement of miR-138 in CFC memory formation, at least partly via the
      regulation of Capn1-mediated synaptic plasticity changes. Therapeutic use of miR
      138/Capn1 is promising as an alternative option in the treatment of fear memory
      related anxiety disorders.

PMID- 30199443
TI  - Long-term Quality of Life and Gastrointestinal Functional Outcomes After
      Pancreaticoduodenectomy.
AB  - OBJECTIVE: To perform a comprehensive assessment of long-term quality of life
      (QOL) and gastrointestinal (GI) function in patients following
      pancreaticoduodenectomy (PD). SUMMARY OF BACKGROUND DATA: Survival after PD has
      greatly improved and thus has resulted in a larger population of survivors, yet
      long-term QOL and GI function after PD is largely unknown. METHODS: Patients were
      identified from a global online support group. QOL was measured using the Short
      Form-36, while GI function was assessed using the Gastrointestinal Symptom Rating
      Scale. QOL and GI function were analyzed across subgroups based on time after PD.
      QOL was compared with preoperative measurements and with established values of a
      general healthy population (GHP). Multivariate linear regression was used to
      identify predictors of QOL. RESULTS: Of the 7605 members of the online support
      group, 1102 responded to the questionnaire with 927 responders meeting inclusion
      criteria. Seven hundred seventeen (77.3%) of these responders underwent PD for
      malignancy. Mean age was 57 +/- 12 years and 327 (35%) were male. At the time of
      survey, patients were 2.0 (0.7, 4.3) years out from surgery, with a maximum 30.7
      year response following PD. Emotional and physical domains of QOL improved with
      time and surpassed preoperative levels between 6 months and 1 year after PD (both
      P < 0.001). Each GI symptom worsened over time (all P < 0.001). Independent
      predictors of general QOL in long-term survivors (> 5 years) included total GSRS
      score [beta = -1.70 (-1.91, -1.50)], female sex [beta = 3.58 (0.67, 6.46)], and
      being a cancer survivor [beta = 3.93 (0.60, 7.25)]. CONCLUSIONS: Long-term QOL
      following PD improves over time, however never approaches that of a GHP. GI
      dysfunction persists in long-term survivors and is an independent predictor of
      poor QOL. Long-term physical, psychosocial, and GI functional support after PD is
      encouraged.

PMID- 30199444
TI  - Responses of Angiogenic Regulators to Resistance Exercise Under Systemic Hypoxia.
AB  - Kon, M, Ikeda, T, Homma, T, and Suzuki, Y. Responses of angiogenic regulators to
      resistance exercise under systemic hypoxia. J Strength Cond Res XX(X): 000-000,
      2018-Resistance exercise and hypoxia powerfully affect the secretions of
      angiogenic regulators. However, the effects of resistance exercise under acute
      systemic hypoxia on circulating levels of angiogenic regulators are unknown.
      Therefore, we investigated the effects of resistance exercise under systemic
      hypoxia on angiogenic regulator responses. Twelve healthy male subjects completed
      2 experimental trials: (a) resistance exercise under normoxia (NRE), and (b)
      resistance exercise under systemic hypoxia (13% oxygen) (HRE) using a hypoxic
      generator. The subjects performed 2 consecutive resistance exercises (bench press
      and bilateral leg press), consisting of 5 sets with 10 repetitions at 70% of 1
      repetition maximum with a 1-minute rest between sets. Serum vascular endothelial
      growth factor (VEGF), matrix metalloproteinase (MMP)-2, MMP-9, and endostatin
      concentrations were measured before exercise (and before exposure to hypoxia in
      the HRE trial) and at 0, 15, and 30 minutes after the resistance exercises. In
      both trials, serum VEGF, MMP-2, MMP-9, and endostatin concentrations
      significantly increased after the exercises compared with preexercise values (p <
      0.05). At 0 minutes after exercise, the percentage change in VEGF concentration
      was significantly higher in the HRE trial compared with that in the NRE trial (p
      < 0.05). However, the exercise-induced changes in MMP-2, MMP-9, and endostatin
      concentrations did not differ between trials. The present results demonstrate
      that acute systemic hypoxia induces a greater resistance exercise-induced VEGF
      response, suggesting that hypoxia plays an important role in increasing the VEGF
      response to a bout of resistance exercise.

PMID- 30199445
TI  - Effects of Time of Day on Race Splits, Kinematics, and Blood Lactate During a 50
      m Front Crawl Performance.
AB  - Lisboa, FD, Raimundo, JAG, Pereira, GS, Ribeiro, G, de Aguiar, RA, and Caputo, F.
      Effects of time of day on race splits, kinematics, and blood lactate during a 50
      m front crawl performance. J Strength Cond Res XX(X): 000-000, 2018-This study
      aimed to investigate the performance, race splits, metabolic, and stroke
      parameters during 2 successive 50-m front crawl under conditions simulating a
      competition. Eleven competitive male swimmers (20 +/- 3 years, 182 +/- 5 cm, and
      77 +/- 5 kg) performed 2 successive 50-m front crawl trials in a 50-m swimming
      pool at 10 AM and 5 PM. Block time (tB), 15-m performance (t.15-m), and 50-m
      performance (t.50-m) were measured. Velocity (V), stroke rate (SR), stroke length
      (SL), and stroke index (SI) were measured at 3 time points during the trials. Pre
      trial and post-trial blood samples were taken to determine blood lactate
      accumulation (Delta[Lac]). For t.50-m, the relative difference between 10 AM and
      5 PM reached 0.1% (p = 0.7; effect size [ES] = 0.02). Furthermore, no differences
      in tB (p = 0.12; ES = -0.28) and t.15-m (p = 0.39; ES = -0.16) were observed
      between periods. Both V (p = 0.11; ES = -0.14) and SI (p = 0.16; ES = 0.15) were
      also similar. Higher values of SR were recorded at 10 AM (p = 0.03; ES = -0.32),
      whereas the morning values of SL were lower (p = 0.04; ES = 0.3). Delta[Lac] was
      not significantly different between periods (p = 0.07; ES = -0.27). Although time
      of the day did not impact performance in 2 successive 50-m front crawl
      performances, different stroke parameters profiles were observed during these
      trials. This may help coaches design specific warm-up exercises to enhance
      performance at different times of the day.

PMID- 30199446
TI  - Physical Characteristics of Elite Youth Female Soccer Players Characterized by
      Maturity Status.
AB  - Emmonds, S, Scantlebury, S, Murray, E, Turner, L, Robsinon, C, and Jones, B.
      Physical characteristics of elite youth female soccer players characterized by
      maturity status. J Strength Cond Res XX(X): 000-000, 2018-The purpose of this
      study was to investigate the influence of maturity status on the physical
      characteristics of youth female soccer players. One hundred fifty-seven players
      from 3 elite soccer academies in England completed assessments of anthropometry,
      strength (isometric midthigh pull), lower-body power (countermovement jump
      [CMJ]), aerobic capacity (Yo-Yo intermittent recovery test level 1), change of
      direction (CoD: 505-left/right), and speed (10 and 30 m). Each player was
      classified into 1 of 6 maturity groups based on their estimated years from peak
      height velocity (YPHV). Magnitude-based inferences were used to assess for the
      practical significance between consecutive groups. Speed, CoD time, CMJ, and
      aerobic capacity were all possibly most likely better in more mature players.
      However, there was a likely difference in relative peak force between maturity
      groups -0.5 YPHV (27.13 +/- 4.24 N.Kg) and 0.5 YPHV (24.62 +/- 3.70 N.Kg), which
      was associated with a likely difference in 10-m sprint time (-0.5 YPHV: 2.00 +/-
      0.12 vs. 0.5 YPHV 2.08 +/- 0.16 seconds) and unclear changes in CMJ and CoD time.
      Findings provide novel comparative data for this cohort relative to maturity
      status and can be used by strength and conditioning coaches to inform the design
      of training programs for youth female soccer players. Strength and conditioning
      coaches should be aware that youth female soccer players may experience a
      decrease in relative strength around peak height velocity, which may impact upon
      the speed, CoD time, and CMJ of players.

PMID- 30199448
TI  - Test-Retest Reliability Between Free Weight and Machine-Based Movement
      Velocities.
AB  - Miller, RM, Freitas, EDS, Heishman, AD, Koziol, KJ, Galletti, BAR, Kaur, J, and
      Bemben, MG. Test-retest reliability between free weight and machine-based
      movement velocities. J Strength Cond Res XX(X): 000-000, 2018-Several devices are
      available to measure muscular power through velocity measurement, including the
      Tendo FitroDyne. The ability for such devices to produce consistent results is
      still questioned, and the reproducibility of measurement between free weight and
      machine exercise has yet to be examined. Therefore, the aim of this investigation
      was to determine the test-retest reliability for barbell velocity during the
      bench press (BP) and weight velocity during the 2 leg press (2LP) for loads
      corresponding to 20-80% of 1 repetition maximum (1RM). Forty recreationally
      active individuals (22.6 +/- 2.5 years; 175.9 +/- 10.8 cm; and 76.2 +/- 13.2 kg)
      with a 1RM BP and 2LP of 66.8 +/- 32.4 kg and 189.5 +/- 49 kg, respectively,
      volunteered for this study. Subjects completed 1 familiarization visit preceding
      3 testing visits, which encompassed 1RM determination and 2 days of velocity
      testing. Forty-eight hours after 1RM testing, the subjects performed 1 repetition
      at 20, 30, 40, 50, 60, 70, and 80% of their 1RM for each exercise in randomized
      order. Subjects returned to the laboratory 1 week later to perform the velocity
      assessment again in randomized order. Intraclass correlation coefficient (ICC2,1)
      and relative SEM for the BP and 2LP ranged from 0.56 to 0.98 (3-18.1%) and 0.78
      to 0.98 (2.8-7.2%), respectively, and no mean differences were observed between
      trials. The results suggest high reliability for BP velocity between 30 and 60%
      1RM and moderate reliability at 20, 70, and 80% 1RM, while the 2LP displayed high
      to excellent reliability from 20 to 80% 1RM. Cumulatively, machine-based exercise
      displayed greater reproducibility; however, additional machine exercises need to
      be examined to bolster this conclusion.

PMID- 30199447
TI  - Very-Short-Duration, Low-Intensity Half-Time Re-warm up Increases Subsequent
      Intermittent Sprint Performance.
AB  - Yanaoka, T, Hamada, Y, Kashiwabara, K, Kurata, K, Yamamoto, R, Miyashita, M, and
      Hirose, N. Very-short-duration, low-intensity half-time re-warm up increases
      subsequent intermittent sprint performance. J Strength Cond Res XX(X): 000-000,
      2018-This study investigated the effect of very-short-duration, low-intensity
      half-time re-warm up (RW) on subsequent intermittent sprint performance. Using a
      randomized cross-over design, 11 healthy men performed 3 trials. In the
      experimental trials, participants performed the first 40-minute intermittent
      exercise followed by a 15-minute half-time. The interventions at half-time were
      15 minutes of seated rest (control), 3 minutes of moderate-intensity RW (cycling
      at 60% of maximal oxygen uptake [V[Combining Dot Above]O2max]; [60% RW]), and 3
      minutes of low-intensity RW (cycling at 30% of V[Combining Dot Above]O2max; [30%
      RW]). After half-time, participants performed the Cycling Intermittent-Sprint
      Protocol (CISP), which consisted of 10 seconds of rest, 5 seconds of maximal
      sprint, and 105 seconds of active recovery at 50% of V[Combining Dot Above]O2max,
      with the cycles repeated over the 20-minute duration. The mean work and
      electromyogram amplitude during the sprint in the CISP were higher in both RW
      trials than in the control trial (p < 0.05). Muscle temperature, estimated from
      the skin temperature, at 60 minutes was higher in the 60% RW trial than in the
      control and 30% RW trials (p < 0.05). The mean change in oxygenated hemoglobin
      concentration during active recovery at 55-65 minutes tended to be higher in both
      RW trials than in the control trial (60% RW trial: p = 0.06, 30% RW trial: p =
      0.06). In conclusion, very-short-duration, low-intensity RW increased
      intermittent sprint performance after the half-time, in comparison with a
      traditional passive half-time practice, and was as effective as a moderate
      intensity RW when matched for total duration.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- 30199449
TI  - Content Validity Index and Reliability of a New Protocol for Evaluation of
      Lifting Technique in the Powerlifting Squat and Deadlift.
AB  - Sjoberg, H, Aasa, U, Rosengren, M, and Berglund, L. Content validity index and
      reliability of a new protocol for evaluation of lifting technique in the
      powerlifting squat and deadlift. J Strength Cond Res XX(X): 000-000, 2018-The aim
      of the study was to create a protocol to cover aspects of technique considered to
      be associated with risk of injury in the powerlifting squat and deadlift and to
      examine the content validity and reliability of the aspects included in the
      protocols. For the content validity investigation, a consensus group of 3
      powerlifting physiotherapists identified the domains of content (risk of injury)
      for 2 protocols (1 for squat and 1 for deadlift) of essential aspects of lifting
      technique through discussions and a review of the literature. Eight selected
      powerlifting experts rated the relevance of each aspect in relation to risk of
      injury (acute or by overuse), and a quantitative estimate of the content validity
      of each aspect was measured through calculations of a Content Validity Index
      (CVI). Aspects of low content validity were discarded, and the remainders were
      evaluated for their inter-rater and intra-rater reliability among 4 experienced
      powerlifters used to coaching and evaluating powerlifting technique. The
      reliability was calculated and analyzed with kappa and percentage of agreement.
      The final protocols included 17 aspects of squat technique and 10 aspects of
      deadlift technique that showed good to excellent CVI and percentage of agreement
      between 64 and 100%. The protocols, formed in this study, will provide evidence
      based recommendations on safe lifting technique for coaches and strength
      practitioners' to use to make relevant assessments and instructions.

PMID- 30199450
TI  - Sex Differences in Resting Metabolic Rate Among Athletes.
AB  - Jagim, AR, Camic, CL, Askow, A, Luedke, J, Erickson, J, Kerksick, CM, Jones, MT,
      and Oliver, JM. Sex differences in resting metabolic rate among athletes. J
      Strength Cond Res XX(X): 000-000, 2018-The purpose of this study was to compare
      differences in resting metabolic rate (RMR) between sexes in Division III
      National Collegiate Athletic Association (NCAA) collegiate athletes and to
      identify predictors of RMR. Sixty-eight male (M) (age: 20.1 +/- 1.5 years;
      height: 181.8 +/- 5.9 cm; body mass (BM): 93.7 +/- 16.3 kg; and body fat%: 16.3
      +/- 8.6%) and 48 female (F) athletes (age: 19.4 +/- 1.3 years; height: 166.5 +/-
      6.0 cm; BM: 63.4 +/- 12.7 kg; and body fat%: 21.5 +/- 6.3%) participated in a
      single day of testing, which included determination of RMR using indirect
      calorimetry and air displacement plethysmography to measure fat mass and fat-free
      mass (FFM). An independent-samples t-test was used to compare differences in body
      composition and RMR between sexes, and regression analysis was used to identify
      predictors of RMR. Men had a significantly higher absolute RMR (M: 2,481 +/- 209
      vs. F: 1,553 +/- 193 kcals.d; p < 0.001), but when adjusted for BM (M: 25.6 +/-
      8.3 vs. F: 25.9 +/- 2.5 kcals.kg BM per day; p = 0.82) and FFM (M: 31.1 +/- 10.6
      vs. F: 33.6 +/- 3.8 kcals.kg FFM per day; p = 0.12), these differences became
      nonsignificant. Regression analysis indicated that BM in both men (beta = 0.73)
      and women (beta = 0.88) was the strongest predictor of RMR. The results of the
      current study indicate minimal differences in RMR between sexes among athletic
      populations when adjusted for BM and FFM. In the current group of athletes, BM
      seems to account for the largest variability in RMR.

PMID- 30199451
TI  - How to Improve Change-of-Direction Speed in Junior Team Sport Athletes
      Horizontal, Vertical, Maximal, or Explosive Strength Training?
AB  - Keller, S, Koob, A, Corak, D, von Schoning, V, and Born, DP. How to improve
      change-of-direction speed in junior team sport athletes-Horizontal, vertical,
      maximal, or explosive strength training? J Strength Cond Res XX(X): 000-000, 2018
      The purpose of the study was to compare the effects of 4 different training
      methods on change-of-direction (COD) speed in junior team sport athletes.
      Specifically, we investigated whether horizontal load training incorporating
      lateral acceleration and deceleration would induce superior performance
      adaptations with respect to COD speed, compared with common vertically oriented
      maximal strength (squats and deadlifts), explosive strength (power clean and high
      pull), and vertical jumping exercises. Male U15 team sport athletes (n = 45) were
      assigned to 1 of 4 groups and performed 2 intervention training sessions per week
      for 4 weeks, in addition to their usual sport-specific training. Before and after
      the training period, COD speed, countermovement and drop jump heights, 1-legged
      lateral jump, and standing long jump performance were assessed. All 4 training
      groups improved COD speed (p <= 0.01, effect size [ES] >=1.35). Countermovement
      and 1-legged lateral jump performance improved with the horizontal load (p <
      0.01, ES = 0.81 and p < 0.01, ES = 1.36), maximal (p = 0.01, ES = 0.56 and p <
      0.01, ES = 1.14), and explosive strength training (p < 0.01, ES = 0.95 and p <
      0.01, ES = 1.60, respectively). The standing long jump improved with the maximal
      (p < 0.01, ES = 1.14) and explosive strength training (p < 0.01, ES = 0.60). In
      conclusion, all 4 training methods improved the COD speed in junior U15 team
      sport athletes. These findings emphasize the importance of well-developed lower
      body strength and power, which contribute to fast COD speed. From a practical
      perspective, conditioning programs for junior athletes can incorporate
      horizontally and vertically oriented exercises with similar effectiveness on COD
      speed.

PMID- 30199452
TI  - Quantification of a Professional Football Team's External Load Using a Microcycle
      Structure.
AB  - Martin-Garcia, A, Gomez Diaz, A, Bradley, PS, Morera, F, and Casamichana, D.
      Quantification of a professional football team's external load using a microcycle
      structure. J Strength Cond Res 32(12): 3520-3527, 2018-The aims of this study
      were to (a) determine the external load of a football team across playing
      position and relative to competition for a structured microcycle and (b) examine
      the loading and variation the day after competition for players with or without
      game time. Training and match data were obtained from 24 professional football
      players who belonging to the reserve squad of a Spanish La Liga club during the
      2015/16 season using global positioning technology (n = 37 matches and n = 42
      training weeks). Training load data were analyzed with respect to the number of
      days before or after a match (match day [MD] minus or plus). Training load
      metrics declined as competition approached (MD-4 > MD-3 > MD-2 > MD-1; p < 0.05;
      effect sizes [ES]: 0.4-3.1). On the day after competition, players without game
      time demonstrated greater load in a compensatory session (MD + 1C) that
      replicated competition compared with a recovery session (MD + 1R) completed by
      players with game time (MD + 1C > MD + 1R; p < 0.05; ES: 1.4-1.6). Acceleration
      and deceleration metrics during training exceeded 50% of that performed in
      competition for MD + 1C (80-86%), MD-4 (71-72%), MD-3 (62-69%), and MD-2 (56
      61%). Full backs performed more high-speed running and sprint distance than other
      positions at MD-3 and MD-4 (p < 0.05; ES: 0.8-1.7). The coefficient of variation
      for weekly training sessions ranged from ~40% for MD-3 and MD-4 to ~80% for MD +
      1R. The data demonstrate that the external load of a structured microcycle varied
      substantially based on the players training day and position. This information
      could be useful for applied sports scientists when trying to systematically
      manage load, particularly compensatory conditioning for players without game
      time.

PMID- 30199453
TI  - Preliminary Investigation Into the Effect of ACTN3 and ACE Polymorphisms on
      Muscle and Performance Characteristics.
AB  - Wagle, JP, Carroll, KM, Cunanan, AJ, Wetmore, A, Taber, CB, DeWeese, BH, Sato, K,
      Stuart, CA, and Stone, MH. Preliminary investigation into the effect of ACTN3 and
      ACE polymorphisms on muscle and performance characteristics. J Strength Cond Res
      XX(X): 000-000, 2018-The purpose of this investigation was to explore the
      phenotypic and performance outcomes associated with ACTN3 and ACE polymorphisms.
      Ten trained men (age = 25.8 +/- 3.0 years, height = 183.3 +/- 4.1 cm, body mass =
      92.3 +/- 9.3 kg, and back squat to body mass ratio = 1.8 +/- 0.3) participated.
      Blood samples were analyzed to determine ACTN3 and ACE polymorphisms. Standing
      ultrasonography images of the vastus lateralis (VL) were collected to determine
      whole muscle cross-sectional area (CSA-M), and a percutaneous muscle biopsy of
      the VL was collected to determine type I-specific CSA (CSA-T1), type II-specific
      CSA (CSA-T2), and type II to type I CSA ratio (CSA-R). Isometric squats were
      performed on force platforms with data used to determine peak force (IPF),
      allometrically scaled peak force (IPFa), and rate of force development (RFD) at
      various timepoints. One repetition maximum back squats were performed, whereby
      allometrically scaled dynamic strength (DSa) was determined. Cohen's d effect
      sizes revealed ACTN3 RR and ACE DD tended to result in greater CSA-M but differ
      in how they contribute to performance. ACTN3 RR's influence seems to be in the
      type II fibers, altering maximal strength, and ACE DD may influence RFD
      capabilities through a favorable CSA-R. Although the findings of the current
      investigation are limited by the sample size, the findings demonstrate the
      potential influence of ACTN3 and ACE polymorphisms on isometric and dynamic
      strength testing. This study may serve as a framework to generate hypotheses
      regarding the effect of genetics on performance.

PMID- 30199454
TI  - Changes in Parameters of Oxidative Stress, Immunity, and Behavior in Endurance
      Athletes During a Preparation Period in Winter.
AB  - Michalickova, D, Minic, R, Kotur-Stevuljevic, J, Andjelkovic, M, Dikic, N, Kostic
      Vucicevic, M, Slanar, O, and Djordjevic, B. Changes in parameters of oxidative
      stress, immunity, and behavior in endurance athletes during a preparation period
      in winter. J Strength Cond Res XX(X): 000-000, 2018-The current study monitored
      markers of immunological and oxidative status in 9 male elite endurance athletes:
      V[Combining Dot Above]O2max: 68 +/- 11 ml.kg.min, age: 24 +/- 2.5 years, and
      training loads: 128 +/- 21 metabolic equivalents-h.wk during a 3-month
      preparation period in winter (January-March). Self-rated state of moods
      evaluation (by Profile of Mood States questionnaire) was performed, and blood
      samples were collected at the beginning and end of the study. Spectrophotometric
      methods and enzyme-linked immunosorbent assay were used for parameters'
      determination. The level of concanavalin A (ConA)-stimulated interferon-gamma
      (IFN-gamma) from peripheral blood mononuclear cells (PBMCs) was increased (562
      [147-852] vs. 1,097 [451-1842] pg.ml, p = 0.013). Also, the level of transforming
      growth factor-1 (TGF-beta1) in serum was elevated (2.5 [1.4-5.1] vs. 7.2 [4.9
      8.2] ng.ml, p = 0.015). There was no change in the level of peptidoglycan (PGN)
      stimulated interleukin (IL)-10 from PBMCs. There were no significant changes in
      PBMCs proliferation/viability on stimulation with ConA and PGN during the study.
      No changes in superoxide dismutase, prooxidative-antioxidative balance, total
      oxidant status (TOS), and thiobarbituric acid reactive substances were observed
      along the study. Total antioxidant status (TAS) was increased (910 +/- 174 vs.
      1,090 +/- 102 MUmol.L, p = 0.018), and activity of paraoxonase (PON1) was
      decreased (523 +/- 295 vs. 335 +/- 183 U.L, p = 0.003) at the end of the study.
      Advanced oxidation protein products were increased (25 +/- 7.9 vs. 42 +/- 7.6
      MUmol.L, p = 0.011). The self-rated sense of vigor significantly declined (20 +/-
      2.1 vs. 14 +/- 3.4, p = 0.045). In conclusion, 3 months of regular training in
      winter induced prominent changes in cytokines, biomarkers of oxidative stress,
      and antioxidative enzyme activity. These changes might increase susceptibility of
      athletes to disease and muscle damage and consequently lead to performance
      reduction.

PMID- 30199455
TI  - Using the Logic Model Framework to Standardize Quality and Rigor in the DNP
      Project.
AB  - BACKGROUND: Since the implementation of the DNP degree, there has been
      controversy, confusion, and inconsistency about the DNP project. To this day, the
      profession lacks a consensus of what the DNP project should be. PROBLEM: Despite
      much in the literature regarding these issues, there is no systematic approach to
      the development of DNP project guidelines. Consequently, there is now an
      escalating interest in increasing the quality and rigor of DNP projects.
      APPROACH: Many issues related to the DNP project can be addressed using a logic
      model approach and incorporating current best practices. CONCLUSIONS: This
      article demonstrates how a logic model can be used for the development or
      improvement of DNP project processes, incorporating best practices and evaluation
      methods to ensure quality and rigor.

PMID- 30199456
TI  - Ossification of the Proximal and Middle Phalangeal Condyles: Radiographic Aid in
      Phalangeal Neck Fracture Reduction.
AB  - BACKGROUND: Phalangeal neck fractures are commonly dorsally displaced and
      angulated. Surgical treatment is often necessary to restore the retrocondylar
      recess. The purpose of this study was to determine whether radiographic landmarks
      can serve as a reference tool for assessing phalangeal neck fracture alignment
      based on age and sex. METHODS: In total, 1061 lateral finger radiographs that
      were interpreted as "normal" by pediatric radiologists in children aged 1 to 18
      years were retrospectively reviewed. The proximal and middle phalanges of each
      digit had a line drawn along the volar cortex [termed the volar phalangeal line
      (VPL)] and a second perpendicular line was drawn at the level of the phalangeal
      condyle. A ratio of the anterior to posterior aspects of the phalangeal condyle
      was determined at the intersection of these lines. Sex of the patients was noted
      to determine whether it influenced the temporal course of ossification. A linear
      regression model was utilized to determine the annual coefficient of growth for
      the phalangeal condyles. RESULTS: There is a temporal course of ossification of
      the proximal and middle phalangeal condyles. As children increase in age, the VPL
      will intersect the phalangeal condyle more dorsally due to the eccentric
      ossification. In children above 9 years of age, the VPL will reliably intersect
      the middle one third of the phalangeal condyle. No clinically significant
      difference exists between the ratios of the proximal and middle phalanges. Sex
      was not associated with a difference in growth. The greatest growth increase was
      observed in the 8 to 9-year-old interval. CONCLUSIONS: The phalangeal condyles
      ossify in an eccentric manner and the VPL will intersect the phalangeal condyle
      more dorsally with increasing age. The VPL and knowledge of where it should
      intersect the phalangeal condyle can be used as a reference guide for evaluating
      the reduction of proximal and middle phalangeal neck fractures in children. LEVEL
      OF EVIDENCE: Level III.

PMID- 30199457
TI  - Minimizing Spine Autofusion With the Use of Semiconstrained Growing Rods for
      Early Onset Scoliosis in Children.
AB  - BACKGROUND: A new growing rod (GR) design, the semiconstrained growing rod
      (SCGR), with the added advantage of axial rotation freedom within the components,
      has been introduced at our center which has been shown to be growth friendly. We
      hypothesize that the SCGR system would reduce autofusion in vivo, thereby
      maximizing the coronal plane correction, T1-S1 growth, and the final correction
      achieved at definitive fusion for children with an early onset scoliosis.
      METHODS: In total, 28 patients had either single or dual 5.5 mm diameter SCGR
      placed minimally invasively through a submuscular approach. Surgical lengthening
      procedures occurred approximately every 6 months until the definitive fusion
      procedure was performed for 18 patients. Scoliosis, kyphosis, and lordosis
      angles, T1-S1 trunk length, and any complications encountered were evaluated.
      RESULTS: For the full cohort, before GR insertion, the mean major Cobb curve
      angle was 72.4 degrees (SD, 18.8; range, 45 to 120), mean T1-S1 trunk length was
      282 mm (SD, 59; range, 129 to 365), and at the latest follow-up (mean 6.9 y, SD
      3.3, range 2.0 to 13.0), 38.8 degrees (SD, 17.5; range 10 to 90) and 377 mm (SD,
      62; range, 225 to 487), respectively. For the subset of 18 patients who have had
      their final instrumented fusion surgery, the definitive surgery procedure alone
      produced a correction of the major Cobb curve angle by mean 20.3 degrees (SD,
      16.1; P<0.0001), and an increase in the T1-S1 trunk length of mean 31.7 mm (SD,
      23.1; P<0.0001). There were 14 complications involving 11 of the 28 patients,
      giving rise to 5 unplanned surgical interventions and 1 case where GR treatment
      was abandoned. CONCLUSIONS: SCGR patients exhibited statistically significant
      increase in T1-S1 trunk length and statistically significant decrease in the
      severity of scoliosis over the course of GR treatment and again, importantly,
      with the definitive fusion surgery, suggesting that autofusion had been minimized
      during GR treatment with relatively low complication rates. LEVEL OF EVIDENCE:
      Level IV-case series.

PMID- 30199458
TI  - Midterm Results of the Ponseti Method for Treatment of Clubfoot in Patients With
      Spina Bifida.
AB  - BACKGROUND: Clubfoot occurs in 30% to 50% of patients with spina bifida. The
      Ponseti casting method has changed treatment of idiopathic clubfoot to a
      primarily nonoperative regimen. The Ponseti method is now widely applied to
      clubfoot in spina bifida, however, few studies report treatment outcomes. Most
      available studies include heterogeneous diagnoses or short-term results. The
      purpose of this study is to report midterm outcomes in patients with spina bifida
      and clubfoot treated with the Ponseti method. METHODS: IRB-approved retrospective
      chart review of 17 consecutive patients (26 feet) below 1 year of age with spina
      bifida and clubfoot treated with Ponseti method. Charts reviewed for age at
      treatment initiation, number of casts, surgeries performed, recurrence of
      deformity, and further treatments. Primary outcome was recurrence of deformity
      requiring further treatment. Data were analyzed using t tests for means and chi
      tests for categorical data. RESULTS: Initial correction was achieved in 26 of 26
      feet patients. A total of 23 of 26 feet patients underwent a surgical procedure
      for the tendo-Achilles at an average age of 105 days, 12 percutaneous tenotomies
      (percT) and 11 open tendonectomy (openT). At average follow-up of 5 (1.8 to 7.5)
      years, 11 feet (42.3%) in 8 patients were successfully treated with Ponseti
      method. Of the 15 feet (57.7%) with recurrence, 10 required posterior releases, 4
      posterior-medial-lateral releases and 1 tendon transfers. Average age at further
      treatment was 1.5 years (0.9 to 3.1 y). Those with recurrence required more casts
      before tendon surgery (7.6 vs. 6.1, P=0.02). A total of 100% patients (12/12)
      with percT had recurrence of deformity, compared with 18% (2/11) of patients with
      openT (P<0.0005). CONCLUSIONS: Midterm evaluation of Ponseti method for clubfoot
      in spina bifida shows a successful outcome in 42.3%. Recurrence with openT was
      significantly lower than percT and also substantially lower than previously
      published recurrence rates in spina bifida (33.3% to 68%). In spina bifida,
      Ponseti method leads to reliable initial correction and is useful to decrease
      extensive soft tissue release. An open excision of the Achilles should be
      performed. Families should be counseled about high risk of recurrence and
      potential need for further treatment. LEVEL OF EVIDENCE: Level III-retrospective
      comparative study.

PMID- 30199459
TI  - Transepiphyseal (Type VII) Ankle Fracture Versus Os Subfibulare in Pediatric
      Ankle Injuries.
AB  - BACKGROUND: Pediatric ankle injuries are common, giving rise to ~17% of all
      physeal injuries. An os subfibulare in a child with an ankle sprain may be
      confused with a type VII transepiphyseal fracture. Here, we evaluate the clinical
      and radiographic features of type VII transepiphyseal fractures to those of os
      subfibulare presenting with acute ankle trauma with the hypothesis that
      radiographs are necessary for final diagnosis and neither clinical history nor
      examination would be diagnostic. METHODS: We performed an internal review board
      approved, retrospective chart review of patients identified with a traumatic os
      subfibulare or type VII ankle fracture over an 18-month period. Charts were
      reviewed for demographics, mechanism, and clinical findings on initial
      presentation. Radiographic measurements of the distal fibular fragment as well as
      epiphysis were made on presenting ankle series radiographs. RESULTS: A total of
      23 patients were identified. Eleven patients had a traumatic type VII ankle
      fracture and 12 had trauma associated with an os subfibulare on initial
      radiographs. The history and clinical presentations were similar and were
      nondiagnostic. The ratio of the width of the fibula at its largest point on the
      anterior posterior view to the width of the fibular fragment was significantly
      larger in the type VII ankle fractures (P=0.05). All os subfibulare were located
      within the inferior third of the epiphysis, whereas all type VII fractures were
      either at the equator or within the middle third of the fibular epiphysis.
      CONCLUSIONS: Radiographs, not clinical presentation, can differentiate an os
      subfibulare from a type VII transepiphyseal fracture. Children with type VII
      fractures have a long, irregular fracture line within the middle third of the
      distal fibular epiphysis. Those with an ankle sprain and os subfibulare have a
      smooth-edged ossicle of relatively short length located within the inferior pole
      of the epiphysis. Furthermore, the radiographic width of the fragment in the type
      VII fractures is significantly larger in width than the os subfibulare. LEVEL OF
      EVIDENCE: Level II.

PMID- 30199460
TI  - Validity, Reliability, and Responsiveness of the Banff Patellar Instability
      Instrument (BPII) in a Adolescent Population.
AB  - BACKGROUND: Health-related quality of life measures for the adolescent patellar
      instability population are limited. The Banff Patella Instability Instrument
      (BPII) is a disease-specific health-related quality of life that has been tested
      on a mixed adult and adolescent population but has not been exclusively tested
      with an adolescent population. The purpose of this study was to determine the
      validity, reliability, and responsiveness of the BPII within an adolescent
      population. METHODS: Content validation was tested with 3 measures: floor and
      ceiling effects; the Cronbach alpha; readability grade level. Reliability was
      measured with an intraclass correlation coefficient (2, k) and the SEM.
      Responsiveness was measured using a 1-way analysis of variance comparing
      preoperative BPII scores to postoperative BPII scores at 6, 12, and 24 months.
      Eta squared was calculated to measure effect size. RESULTS: The BPII demonstrated
      no floor or ceiling effects. The Cronbach alpha for the BPII ranged from 0.97 to
      0.98 for the preoperative and postoperative time periods. The readability index
      was a mean grade level of 8.9. Test-retest reliability assessment demonstrated an
      intraclass correlation coefficient (2, k) of 0.99 indicating strong reliability.
      The SEM was 1.3. There was a statistically significant difference in BPII scores
      for the 4 different time interval measures (F3, 176=50.04; P<0.001). Eta squared
      was 0.46 demonstrating a moderate to large effect. CONCLUSIONS: The BPII
      demonstrated validity, reliability, and responsiveness in an adolescent
      population. Furthermore, it has demonstrated an appropriate cognitive reading
      grade level of 8.9, commensurate with the mean age (16.08 y) of the population
      tested. LEVEL OF EVIDENCE: Level III.

PMID- 30199462
TI  - Epidemiology of Slipped Capital Femoral Epiphysis in Ontario, Canada.
AB  - BACKGROUND: Slipped capital femoral epiphysis (SCFE) is a well-characterized
      disorder of the hip seen in adolescent patients. It is characterized by deformity
      secondary to failure through the proximal femoral growth plate, which results in
      posterior-inferior displacement of the epiphysis on the proximal femoral
      metaphysis. Long-term sequelae of SCFE may include osteonecrosis, residual
      deformity, leg length discrepancy, degenerative joint disease, and chronic pain.
      The long-term consequences of SCFE may be the source of significant morbidity for
      the patient, and depending of the local incidence of this condition, may
      represent a significant expenditure of health care resources. Historically, the
      true incidence of SCFE within Ontario has been approximated using US-based
      studies of arguably comparable patient populations. In our study, we aimed to
      characterize the epidemiology of SCFE in the province of Ontario. METHODS: We
      used a prospectively collected, not-for-profit Ontario research database to
      identify recorded cases of SCFE between April 1, 2002 and March 31, 2011.
      Specifically, we identified all hospital discharges with an ICD-9 or 10
      diagnostic codes for SCFE in the Canadian Institute for Health Information
      Discharge Abstract database. RESULTS: Over the 10-year study period, there were
      648 cases of SCFE with an average annual incidence rate of 5.68/100,000 in
      Ontario. CONCLUSIONS: We have observed a trend toward decreasing incidence rates
      of SCFE in Ontario over the last 10 years. The determination for the underlying
      causes for the changing trends of SCFE may be relevant for initiating public
      health campaigns directed at reducing the incidence of SCFE LEVEL OF EVIDENCE::
      Level IV-epidemiological study.

PMID- 30199461
TI  - Height-Width Ratio of Proximal Femoral Epiphysis: Estimation of Lateral Pillar
      Involvement in Bilateral Perthes Disease.
AB  - BACKGROUND: The standard evaluation of epiphyseal involvement in Perthes disease
      is lateral pillar classification. However, it needs to be compared with
      contralateral normal hip leading to limited use in bilateral disease. We,
      therefore, develop a ratio between epiphyseal height and metaphyseal width of
      affected hips to estimate lateral pillar involvement. This study aimed to assess
      the height-width ratio of the proximal femoral epiphysis in non-Perthes children,
      and to find the relationship between the height-width ratio and lateral pillar
      classification in Perthes disease. METHODS: A cross-sectional study was conducted
      between 2009 and 2015. Phase I included children aged 2 to 15 years who did not
      have Perthes disease. Phase II included children aged 2 to 15 years who had
      Perthes disease. Other abnormal proximal femoral epiphysis was excluded. Lateral
      pillar height and metaphyseal width were independently measured twice by 2
      assessors in each phase. Intraobserver and interobserver levels of agreement,
      height-width ratio and cut-off points to differentiate lateral pillar types were
      determined. RESULTS: There were 69 children (87 hip radiographs) who had non
      Perthes hips, and 18 boys with Perthes disease (20 hip radiographs). Height-width
      ratio in the non-Perthes group increased from 0.38 to 0.48 at 2 to 10 years of
      age and remained constant until maturity. Average height-width ratio in lateral
      pillar A/non-Perthes hip was 0.47+/-0.05, lateral pillar B or B/C 0.32+/-0.05,
      and lateral pillar C 0.18+/-0.05. Intraobserver and interobserver level of
      agreements of height-width ratio in Perthes disease were 0.007 (95% confidence
      interval, -0.030 to 0.043) and 0.006 (95% confidence interval, -0.119 to 0.107),
      respectively. Cut-off values to differentiate lateral pillar A and B or B/C was
      0.40, and to differentiate lateral pillar B or B/C, and C was 0.25 with 90%
      accuracy and area under receiver operating characteristic curve of 0.9.
      CONCLUSIONS: Height-width ratio is useful for grading severity in unilateral and
      bilateral Perthes disease. It has excellent reliability and validity with exact
      cutoff values to estimate lateral pillar classification. LEVEL OF EVIDENCE: Level
      II-diagnostic study.

PMID- 30199463
TI  - Effect of Antiplatelet/Anticoagulant Use on Glaucoma Progression in Eyes With
      Optic Disc Hemorrhage.
AB  - PURPOSE: To assess whether the use of antiplatelets (APs)/anticoagulants (ACs)
      affects glaucoma progression in eyes with optic disc hemorrhage (DH). METHODS:
      One hundred and nineteen eyes from 119 patients with primary open-angle glaucoma
      in whom a DH was observed at least once during the follow-up period (mean follow
      up duration: 6.2 y) were included in this retrospective observational study. Cox
      proportional hazard models were used to identify the association between putative
      factors, including AP/AC use, and glaucoma progression. Glaucoma progression was
      assessed on the basis of changes noted on serial optic disc and retinal nerve
      fiber layer photographs or changes in the visual field. RESULTS: Nineteen of the
      119 patients took AP/AC drugs daily [AP/AC use group (AG)], while the others did
      not [no use group (NG)]. The follow-up period to progression was significantly
      different between the 2 groups (61.2+/-23.5 mo for the AG and 47.6+/-22.0 mo for
      the NG; P=0.016). Kaplan-Meier analysis revealed a greater cumulative probability
      of glaucoma progression in the NG than in the AG, with borderline statistical
      significance (P=0.081). Higher mean intraocular pressure during the follow-up
      period was a risk factor for glaucoma progression (hazard ratio, 1.107; P=0.014),
      while AP/AC drug use protected against glaucoma progression (hazard ratio, 0.576;
      P=0.046). CONCLUSIONS: According to our result, use of AP/AC drugs was associated
      with lower risk of glaucoma progression in eyes with DH.

PMID- 30199464
TI  - Long-term Safety and Efficacy of Conjunctival Pedicle Graft Revision Combined
      With Repeated Pericardium Allograft for Exposed Glaucoma Drainage Devices.
AB  - PURPOSE: To investigate the safety and long-term results of conjunctival pedicle
      graft (CPG) technique for revision of exposed glaucoma drainage device (GDD).
      DESIGN: Retrospective noncomparative case series. PATIENTS AND METHODS: All
      patients with exposed GDD between 2011 and 2016 who underwent tube revision with
      CPG were included. Data from demographic variables, glaucoma subtype, previous
      surgeries, GDD type and location, patch graft nature, intraocular pressure, and
      intraoperative and long-term complications were collected. RESULTS: Eight eyes
      from 7 patients met the inclusion criteria. Median age was 61 years old (range,
      51 to 80), median time to erosion was 23.4 months (range, 5 d to 45.1 mo), median
      number of operations before exposure was 3 (range, 1 to 5), and 6 tubes had an
      inferior location (75%). Average follow-up after repair was 24.3 months (range,
      5.2 to 59.8 mo). No significant intraoperative adverse events were noted and
      visual acuity, intraocular pressure, and number of medications remained unchanged
      at 1 month after repair in all cases. We report 1 case of repeated tube exposure
      24 months after CPG in a 51-year-old Afro-Caribbean woman with 5 previous
      operations. CONCLUSIONS: With an average follow-up of >2 years, we provide
      additional long-term evidence that CPG is a safe and effective technique for
      treating exposed tubes. We did not experience any complications and report 1
      reexposure case in a young Afro-Caribbean patient with extensive previous
      conjunctival scarring.

PMID- 30199465
TI  - Interocular Asymmetry of Minimum Rim Width and Retinal Nerve Fiber Layer
      Thickness in Healthy Brazilian Individuals.
AB  - PURPOSE: To determine interocular differences in Bruch's membrane opening minimum
      rim width (BMO-MRW) and retinal nerve fiber layer thickness (RNFLT) in healthy
      Brazilian individuals. MATERIALS AND METHODS: Both eyes of 220 healthy
      individuals were included in this observational, cross-sectional study. All
      individuals had normal clinical examination and visual fields. Global and
      sectorial interocular BMO-MRW and RNFLT differences, acquired and regionalized
      relative to the fovea to BMO center (FoBMO) axis, were calculated. The effect of
      age, axial length, and BMO area asymmetry on the parameters' asymmetry was
      evaluated. RESULTS: The 95th limits for interocular BMO-MRW and RNFLT global
      differences were 49 and 9 MUm, respectively. BMO-MRW asymmetry was negatively
      correlated (beta=-33.87 MUm/mm, R=0.06, P<0.001), whereas RNFLT asymmetry was
      positively correlated (beta= 6.13 MUm/mm, R=0.09, P<0.001) with BMO area
      asymmetry. Neither BMO-MRW nor RNFLT asymmetries were correlated with axial
      length asymmetry (beta=-16.90 MUm/mm, R=0.00, P=0.15; beta=-1.18 MUm/mm, R=0.00,
      P=0.52, respectively). Similarly, BMO-MRW and RNFLT asymmetries were not
      correlated with age (beta=0.17 MUm/y, R=0.01, P=0.22; beta=0.0 MUm/y, R=0.00,
      P=0.19, respectively). CONCLUSIONS: Our results suggest that global BMO-MRW and
      RNFLT interocular differences exceeding 49 and 9 MUm, respectively, may indicate
      statistically abnormal asymmetry, which may suggest early structural damage.
      Asymmetry in BMO area should be accounted for when considering interocular
      asymmetry in BMO-MRW and RNFLT.

PMID- 30199466
TI  - A Message to All Readers of the Journal of Glaucoma.

PMID- 30199467
TI  - Heritability of Anterior Chamber Indices in Rural Population.
AB  - OBJECTIVE: To examine the heritability of the anterior chamber depth, angle, and
      volume as well as the corneal volume and diameter using Pentacam in households
      living in underserved rural areas of Iran. MATERIALS AND METHODS: This cross
      sectional population-based study was conducted in randomly selected households
      living in 2 rural districts in the south and north. The data of subjects above 5
      years and households in which at least 2 members (father or mother and a child)
      had Pentacam data were analyzed. Each subject underwent a comprehensive
      ophthalmic examination, with emphasis on the measurement of visual acuity and
      refraction, biomicroscopy, and Pentacam imaging. Heritability was estimated to
      investigate familial aggregation of anterior chamber indices, and the effects of
      age, sex, and living area were controlled for as confounding factors. RESULTS: Of
      the 3851 selected individuals, 3314 participated in the study. After applying the
      exclusion criteria, the data of 1383 subjects from 382 households were included
      in the analysis. The mean age of the participants was 37.23+/-19.35 years (range,
      6 to 93 y). The highest and lowest heritability estimates were related to the
      anterior chamber angle (72%) and corneal diameter (28%), respectively. The
      heritability percentages of the anterior chamber depth, anterior chamber volume,
      and corneal volume were 47%, 39%, and 57%, respectively. CONCLUSIONS: The high
      heritability of the anterior chamber angle points to a high correlation between
      this phenotype and genetic factors. Further genetic and molecular investigations
      are suggested to find the related genes and understand the etiology of glaucoma.

PMID- 30199468
TI  - Employee Perceptions of Safety, Health, and Well-Being: Focus Group Findings From
      One Veterans Affairs Medical Center.
AB  - OBJECTIVE: Focus groups were conducted at one veterans affairs (VA) medical
      center to understand (1) how the work environment and conditions of work
      influence employee safety, health, and well-being; (2) what programs, policies,
      and practices promote and protect employee safety and health in VA; and (3) how
      employee safety, health, and well-being impact the organizational mission.
      METHODS: Nine focus groups were conducted with leadership, supervisor, and
      frontline employees. Focus groups were audio recorded, transcribed, and content
      analysis was performed. RESULTS: Fifty-five employees participated in the focus
      groups. Six common themes emerged-stressful working conditions, health hazards,
      organizational factors, current program knowledge, participation barriers, and
      program suggestions. CONCLUSIONS: Employees identified organizational and
      structural elements of work that impact safety, health, and well-being.
      Application of the Total Worker HealthTM hierarchy of controls provided a novel
      framework for discussion of focus group findings.

PMID- 30199469
TI  - Cognitive and Affective Insecurity Related to Remaining Employed and Working
      Conditions: Their Associations With Mental and General Health.
AB  - OBJECTIVE: The present study aims to tackle in detail the associations of
      insecurity with mental and self-rated health by using cognitive and affective
      measures of insecurity that focus on different aspects such as job loss,
      difficulties in finding an alternative job, and worsening the working conditions.
      METHODS: Data come from a representative sample of the Spanish salaried working
      population (n = 1807) obtained by the 2016 Psychosocial Risks Survey. RESULTS:
      Cognitive measures yield stronger associations between job loss and labor market
      insecurity and health, whereas the association between insecurity over worsening
      job conditions and health is stronger when using affective measures, the
      associations with mental health being stronger in both cases than those involving
      self-rated health. CONCLUSION: Association with health varies, in strength and at
      times in direction, depending on how insecurity is measured and conceptualized.

PMID- 30199470
TI  - Direct and Indirect Costs Among United States Commercially Insured Employees With
      Migraine.
AB  - OBJECTIVE: To compare direct, indirect, and societal (direct plus indirect) costs
      between patients with and without migraine (controls). METHODS: Patients with
      migraine were identified from MarketScan claims and Health and Productivity
      Management databases from 01/01/2010-12/31/2013, and were propensity score
      matched (1:1) to controls. RESULTS: Patients with migraine (N = 26,647) were
      matched to controls, of which 4,323 were matched for work absence and 26,212 for
      short-term disability eligibility. Mean annualized direct costs ($13,032 vs
      $3,234), indirect costs due to absence ($4,104 vs $3,531) and short-term
      disability ($1,131 vs $52), and societal costs due to absence ($16,043 vs $6,938)
      and short-term disability ($14,278 vs $3,182) were all significantly higher (P <
      0.001) for those patients with migraine versus controls, respectively.
      CONCLUSIONS: Migraine imposes high direct and indirect economic burden on payers
      and society due to significantly higher work productivity loss compared to
      controls.

PMID- 30199471
TI  - Work Practices and Respiratory Health Status of Appalachian Coal Miners With
      Progressive Massive Fibrosis.
AB  - OBJECTIVE: The aim of this study was to characterize workplace practices and
      respiratory health among coal miners with large opacities consistent with
      progressive massive fibrosis (PMF) who received care at a federally funded black
      lung clinic network in Virginia. METHODS: Participants were interviewed about
      their workplace practices and respiratory health. Medical records were reviewed.
      RESULTS: Nineteen former coal miners were included. Miners reported cutting rock,
      working downwind of dust-generating equipment, nonadherence to mine ventilation
      plans (including dust controls), improper sampling of respirable coal mine dust
      exposures, working after developing respiratory illness, and suffering from
      debilitating respiratory symptoms. CONCLUSION: Consistent themes of suboptimal
      workplace practices contributing to development of PMF emerged during the
      interviews. Some of the practices reported were unsafe and unacceptable. Further
      research is needed to determine the prevalence of these factors and how best to
      address them.

PMID- 30199472
TI  - Baseline risk assessment of patients with ulcerative colitis: does initial
      treatment selection influence outcomes?
AB  - BACKGROUND AND AIMS: Treatment of ulcerative colitis (UC) typically follows a
      step-up approach and targets colonic mucosal healing. Although mucosal healing
      reduces the risk of colectomy, whether or not early treatment of patients with
      'high-risk' features using tumor necrosis factor (TNF) antagonists reduces the
      risk of colectomy is not clear. Accordingly, we aim to evaluate the effect of
      baseline treatment selection according to the risk profile on 5-year outcomes and
      identify predictors of poor outcomes. PATIENTS AND METHODS: Adult patients with
      confirmed UC were retrospectively identified. Baseline clinical and endoscopic
      data were collected. Patients were assigned a risk profile on the basis of the
      presence or absence of 'high-risk' features within the first 6 months of
      diagnosis including moderate to severe endoscopic disease, frequent need for
      steroids, steroid dependency, and disease involving the entire colon according to
      endoscopy. Treatment discordance was defined as treating 'high-risk' patients
      with medications other than anti-TNF therapy during the first 6 months after
      diagnosis or treating 'low-risk' patients with anti-TNF therapy within 6 months
      of diagnosis. The associations between discordance and 5-year colectomy and
      hospitalization rates were statistically calculated through regression analysis,
      as were predictors of outcomes. RESULTS: A total of 108 patients were identified
      and studied. The median age was 36 years (interquartile range=27-50) and the
      average duration of disease was 6.6 (+/-3.1) years. Females comprised 62% of the
      cohort and 30% reported cigarette smoking. Seventy three percent of the patients
      were placed in the 'high-risk' category. The 5-year risk of colectomy was not
      statistically significantly higher in patients identified as 'high-risk' compared
      with those who were 'low-risk' (risk ratio=0.86, 95% confidence interval=0.24
      3.1, P=0.81), nor was the 5-year risk of hospitalizations (risk ratio=1.63, 95%
      confidence interval=0.81-3.30, P=0.15). On the basis of stepwise model selection,
      colectomy was significantly predicted by discordance (P=0.039), arthritis
      (P=0.007), baseline stool frequency (P=0.019), Adalimumab use within the first 6
      months of diagnosis (P=0.006), and pyoderma gangrenosum (P=0.049);
      hospitalization was predicted by discordance (P=0.018), baseline albumin
      concentrations (P=0.005), thromboembolism (P<0.005), thiopurine use within the
      first 6 months of diagnosis (P<0.005), Adalimumab use within the first 6 months
      of diagnosis (P=0.003), nationality (P=0.016), endoscopic severity (P=0.007),
      arthritis (P=0.005), and pyoderma gangrenosum (P=0.025). CONCLUSION: Among other
      clinical parameters, discordance between baseline risk and treatment selection
      appears to be a significant predictor of outcomes in UC.

PMID- 30199473
TI  - Tumor behavior of hepatocellular carcinoma after hepatitis C treatment by direct
      acting antivirals: comparative analysis with non-direct-acting antivirals-treated
      patients.
AB  - INTRODUCTION: Scarce reports have commented on hepatocellular carcinoma (HCC)
      behavior after direct-acting antivirals (DAAs). AIM: To analyze differences in
      tumor behavior between patients with hepatitis C virus (HCV)-induced HCC and were
      either treated or not using DAAs. PATIENTS AND METHODS: This case-control study
      includes patients with HCV-related HCC who received generic DAAs (group I) and
      all non-DAA treated patients with HCC who presented to our clinic during the same
      period (group II). Patient and tumor characteristics, treatment types and outcome
      were compared between the two groups. RESULTS: Group I included 89 patients and
      group II included 207 patients. No significant difference was detected between
      groups regarding HCC number or size. Group I showed a more infiltrative HCC
      pattern, whereas group II had more circumscribed and delineated lesions. The
      incidence of portal vein thrombosis and significant lymphadenopathy was
      significantly higher in group I (P=0.03 and 0.03, respectively). Serum levels of
      alpha-fetoprotein were significantly higher in group I (P=0.02). These factors
      significantly affected the response to HCC management (P=0.03). Incidence of
      complete responses were 47.2 and 49.8% for groups I and II, respectively, whereas
      incomplete responses were 12.4 and 25.1%, respectively. Supportive treatment was
      applied to 40.4% in group I and 25.1% in group II. CONCLUSION: HCC behavior was
      more aggressive in DAA-treated patients regarding portal vein thrombosis,
      malignant lymphadenopathy, and HCC imaging characteristics, which affected the
      chance of ablation and the treatment response.

PMID- 30199474
TI  - Compound heterozygous mutations in IL10RA combined with a complement factor
      properdin mutation in infantile-onset inflammatory bowel disease.
AB  - OBJECTIVES: Inflammatory bowel diseases (IBDs) are chronic and multifactorial
      diseases resulting from a complex interaction of host genetic factors and
      environmental stimuli. Although many genome-wide association studies have
      identified host genetic factors associated with IBD, rare Mendelian forms of IBD
      have been reported in patients with very early onset forms. Therefore, this study
      aimed to identify genetic variants associated with infantile-onset IBD.
      PARTICIPANTS AND METHODS: We obtained genomic DNA from whole blood samples of a
      male patient with infantile-onset IBD and nonconsanguineous Korean parents. Whole
      exome sequencing was performed using trio samples. Then, we analyzed the data
      using susceptibility genes for monogenic forms of IBD and various
      immunodeficiencies and protein structural analysis. RESULTS: The patient who
      presented with oral aphthous ulcers at the age of 14 days suffered from severe
      colitis and was refractory to medical treatment. Compound heterozygous mutations
      in IL10RA (p.R101W; p.T179T) were found in the patient. In addition, a hemizygous
      mutation in complement factor properdin (CFP) (p.L456V) located on the X
      chromosome was detected, inherited from the patient's mother. Protein structural
      modeling suggested impaired properdin subunit interactions by p.L456V that may
      hamper protein oligomerization required for complement activation. CONCLUSION:
      This study identified compound heterozygous mutations in IL10RA combined with a
      hemizygous CFP mutation in infantile-onset IBD by using whole-exome sequencing.
      CFP p.L456V may exacerbate symptoms of infantile-onset IBD by disturbing
      oligomerization of properdin.

PMID- 30199475
TI  - Evaluation of US Orthopaedic Surgery Academic Centers Based on Measurements of
      Academic Achievement.
AB  - INTRODUCTION: Although a variety of agencies have attempted to evaluate the
      academic achievements of orthopaedic surgery academic centers, most use opaque
      criteria that are difficult to interpret and do not provide clear targets for
      improvement. This study leverages a weighted algorithm using objective
      measurements that has been linked to academic achievement to attempt to provide a
      comprehensive assessment of scholarly accomplishment for orthopaedic surgery
      academic centers. METHODS: We examined full-time faculty at 138 US orthopaedic
      surgery academic centers; part-time or volunteer faculty were excluded. Five
      metrics of academic achievement were assessed: National Institutes of Health
      funding (2013), number of publications, Hirschberg-index (ie, a metric of impact
      of publications), leadership positions held in orthopaedic surgery societies, and
      editorial board positions of top orthopaedic and subspecialty journals. Academic
      programs were given a score for every category, and the algorithm was used to
      calculate an overall score of academic achievement for each program. RESULTS: The
      five most academically productive programs were Washington University in St.
      Louis, Hospital for Special Surgery, Mayo Clinic, University of Pennsylvania, and
      Thomas Jefferson University. CONCLUSION: This algorithm may provide faculty with
      an assessment tool that can establish benchmarks to help focus efforts toward
      increasing the academic productivity of their respective programs.

PMID- 30199476
TI  - Symptomatic, Unstable Os Acromiale.
AB  - Management of a persistently symptomatic, unstable os acromiale remains
      controversial. An unstable os acromiale is an easy diagnosis to miss and should
      be specifically evaluated for in patients with shoulder pain and a high degree of
      clinical suspicion. Surgical options include open or arthroscopic excision and
      open reduction and internal fixation. Open excision of large fragments has had
      poor results. Arthroscopic treatment is commonly used for small fragments
      (preacromion), and the technique has also been used in larger fragments (meso
      os), but concerns persist over postoperative weakness secondary to shortening of
      the deltoid lever arm. Open reduction and internal fixation through a
      transacromial approach has been shown to have predictable union rates but can be
      complicated by symptomatic implant. Recent biomechanical studies have expanded
      our understanding of optimal fixation constructs, which may also decrease implant
      related issues. Ultimately, the choice of which procedure to use will be dictated
      by patient factors such as age, activity level, and the nature of rotator cuff
      pathology. LEVEL OF EVIDENCE:: Level V.

PMID- 30199477
TI  - Treatment Patterns and Outcomes of Stable Hips in Infants With Ultrasonic
      Dysplasia.
AB  - INTRODUCTION: No clear practice guideline exists for the management of stable hip
      with ultrasonic dysplasia (UD). This study assessed the treatment patterns for
      stable UD and determined the outcomes of Pavlik harness (PH) treatment or
      observation (OB). METHODS: This is a prospective study of 80 infants (107 hips)
      aged <=12 weeks at presentation diagnosed with stable UD. RESULTS: Sixty-five
      hips were treated with PH, whereas 42 hips were observed. Patients who were older
      at the time of initial sonogram and those with lower head coverage were more
      likely to be treated with PH. The mean head coverage was lower in the PH group,
      indicating more severe UD. At a 2-year follow-up period, 93% of patients in the
      OB group and 87% in the PH group had a good radiographic outcome. DISCUSSION:
      Head coverage and age at first sonogram had a significant influence on the
      treatment decision for PH. A milder ultrasonic hip dysplasia can be observed
      because 93% of the patients who were observed had a good outcome. LEVEL OF
      EVIDENCE: Level II: prospective cohort study.

PMID- 30199478
TI  - Risk Factors for Prolonged Postoperative Opioid Use After Spine Surgery: A Review
      of Dispensation Trends From a State-run Prescription Monitoring Program.
AB  - INTRODUCTION: Opioid abuse and dependence have a detrimental effect on elective
      orthopaedic surgeries, yet pain control is an important predictor of
      postoperative satisfaction. We aimed at better defining risk factors for
      prolonged postoperative opioid requirements and risk factors for patients
      requiring higher doses of opioids after spine surgery. METHODS: The Illinois
      Prescription Monitoring Program was queried to analyze opioid dispensation
      patterns at 3 and 6 months postoperatively for adult patients who had spine
      surgery at a tertiary care hospital by a single surgeon over a 5-year period.
      Patients were divided into three groups: group 1 patients had opioid dispensed to
      them 3 and 6 months preoperatively, group 2 patients had opioid dispensed to them
      only at 3 months preoperatively, and group 3 patients did not have preoperative
      opioid prescriptions. Demographic characteristics, psychiatric history, smoking
      status, alcohol use, body mass index, surgical region, and presence of multiple
      prescribers were abstracted. Statistical analysis included multivariate modified
      Poisson regression, linear regression, and chi-squared testing when appropriate.
      RESULTS: Patients in group 1 were at significantly increased risk of continued
      opioid usage than those in group 2 (relative risk, 3.934; 95% confidence
      interval, 1.691 to 9.150; P = 0.0015) and those in group 3 (relative risk, 4.004;
      95% confidence interval, 1.712 to 9.365; P = 0.0014) at 6 months postoperatively.
      Group 1 patients also had larger quantities of opioid dispensed to them relative
      to patients in group 2 or group 3 (P < 0.0001) at 6 months postoperatively.
      DISCUSSION: Use of opioid medications at 6 months preoperatively is a risk factor
      for continued usage and at higher doses 6 months postoperatively. LEVEL OF
      EVIDENCE: Level III: retrospective cohort study.

PMID- 30199479
TI  - Vaccine Strain Varicella Infection in an Infant with Previously Undiagnosed
      Perinatal Human Immunodeficiency Type-1 Infection.
AB  - A 15-month-old infant with a history of developmental delay and weight loss with
      multiple hospital admissions was diagnosed with a pustular lesion identified as
      vaccine strain varicella at the vaccination site. He was ultimately determined to
      be HIV infected following a protracted evaluation which did not initially include
      HIV since his mother was confirmed HIV seronegative at 3 months gestation.

PMID- 30199480
TI  - Utility of Clinical and Laboratory Decision Rules in Identifying Bacterial
      Meningitis Among Children With suspicion of Central Nervous System Infections in
      a Malaria-Endemic Area, Mbarara Uganda.
AB  - Several decision rules combining clinical and biological parameters have been
      proposed to distinguish bacterial from aseptic meningitis, but have not been
      evaluated in Africa. In children hospitalized with suspected central nervous
      system infections in Uganda, we found that the Bacterial Meningitis Score and
      Meningitest showed lower performance than in European children, and that a
      decision rule designed specifically using parameters associated with bacterial
      meningitis also showed inadequate diagnostic performance for clinical use.

PMID- 30199481
TI  - Invasive Candidiasis in Pediatric Intensive Care Unit: More Challenges.

PMID- 30199482
TI  - Mobile, Population-wide, Hybrid HIV Testing Strategy Increases Number of Children
      Tested in Rural Kenya and Uganda.
AB  - Efficient ways to identify children with HIV in the context of universal test-and
      treat policies are needed. We evaluated a hybrid testing strategy combining
      mobile community and home-based HIV testing in 87,700 children across 32 rural
      communities in 2 East African countries. This approach resulted in 81% testing
      coverage of at-risk children and doubled the number of children diagnosed with
      HIV.

PMID- 30199483
TI  - Is Polymerase Chain Reaction in Neonatal Dried Blood Spots Reliable for the
      Diagnosis of Congenital Cytomegalovirus Infection?
AB  - BACKGROUND: Detection of cytomegalovirus (CMV) DNA by real-time polymerase chain
      reaction (rt-PCR) in dried blood spots (DBS) collected for newborn screening has
      been assessed for retrospective diagnosis of congenital CMV (cCMV) infection,
      with variable results (sensitivities ranging from 34% to 100%). We aimed to
      assess the accuracy of this technique in Spain in a large patient series.
      METHODS: Ambispective, multicenter study including patients with confirmed cCMV
      from the Spanish Registry of cCMV patients (REDICCMV). cCMV was established on
      the presence of CMV DNA in any body fluid, by positive culture findings, or by
      molecular techniques during the first 2 weeks of life. Children in whom cCMV had
      been excluded were used as negative controls. Neonatal DBS samples were collected
      from both groups. The presence of CMV DNA was assessed by rt-PCR (RealStar CMV,
      Altona, Hamburg, Germany) in a central laboratory. RESULTS: One-hundred and three
      patients and 81 controls from 10 hospitals were included. The performance of CMV
      DNA determination in DBS for the diagnosis of cCMV was as follows (95% CI):
      sensitivity 0.56 (0.47-0.65), specificity 0.98 (0.91-0.99), positive likelihood
      ratio 22.81 (5.74-90.58), negative likelihood ratio 0.45 (0.36-0.56). Sensitivity
      increased with the birth viral load (bVL) log category. In cCMV patients, lower
      bVL was the single variable associated with a negative DBS rt-PCR result
      (p=0.017). CONCLUSION: The sensitivity of CMV rt-PCR in DBS in our series was low
      and correlated with the bVL. Thus, a negative DBS result would not rule out cCMV
      infection, especially in patients with a low viremia level at birth.

PMID- 30199485
TI  - Harnessing Analytic Morphomics for Early Detection of Pancreatic Cancer.

PMID- 30199484
TI  - Reactivity of Routine HIV Antibody Tests in Children with Perinatally-Acquired
      HIV-1 in England: Cross Sectional Analysis.
AB  - We assessed HIV antibody prevalence in children with perinatally-acquired HIV
      (PaHIV) in England. 18%(10/55) of those starting combination antiretroviral
      therapy (cART) <6 months of age were seronegative, and had lower viral load at
      diagnosis and cART start, and fewer viral rebounds, than 45/55 seropositives.
      Implications for patient selection for HIV cure research, and interpretation of
      routine antibody testing, are discussed.

PMID- 30199486
TI  - Role of Radiological Imaging in the Diagnosis and Characterization of Pancreatic
      Cystic Lesions: A Systematic Review.
AB  - The evidence on the ability of radiological tests to predict a specific diagnosis
      and also their aptitude in identifying pathological markers indicative of
      malignancy in cystic lesions of the pancreas remains inconclusive. We conducted a
      systematic review on MEDLINE for the use of computed tomography (CT), magnetic
      resonance imaging, and positron emission tomography/CT (PET/CT) in the diagnosis
      and characterization of these cysts. The accuracy of CT scan for reaching a
      specific diagnosis was 39% to 61.4%, whereas its accuracy for differentiating
      benign from malignant lesions was 61.9% to 80%. Magnetic resonance imaging showed
      a better accuracy in identifying a specific diagnosis of 50% to 86%, whereas its
      accuracy in differentiating benign from malignant lesions was 55.6% to 87%. The
      use of magnetic resonance imaging was superior to CT scan in identifying
      septations, mural nodules, and ductal communication. The sensitivity of PET/CT in
      diagnosing malignancy was 85.7% to 100% with a reported accuracy of 88% to 95%.
      The evidence gathered from this review suggests that the adequacy of CT imaging
      in full characterization of pancreatic cysts is suboptimal, and therefore a low
      threshold for supplementary imaging is advised. The use of PET/CT should be
      considered in high-risk patients with equivocal findings.

PMID- 30199487
TI  - Pancreatic Cancer-Associated Depression: A Case Report and Review of the
      Literature.
AB  - The prevalence of major depressive disorder (MDD) in pancreatic cancer (PC) has
      been reported up to 7 times higher than the general population. Despite repeated
      studies that show worse quality of life, survival outcomes, and treatment
      compliance in cancer patients with depression, baseline antidepressant use ranges
      from 15% to 27%. A meta-analysis of 6 prospective trials specific to PC estimates
      that 43% of patients with PC experience depression after diagnosis. This is
      especially alarming in patients with PC, who may experience a prodrome of
      symptoms including depression and loss of drive. In fact, this prodrome of
      symptoms may very well be due to an overexpression of indoleamine 2,3-dioxgenase,
      an enzyme in the kynurenine pathway that leads to serotonin depletion and the
      buildup of cytotoxic metabolites in the brain. In this literature review, we
      outline all previous studies pertinent to PC and depression, as well as the
      molecular underpinnings that may contribute to states of depression, and report
      on previous randomized control trials in cancer populations that investigate the
      use of antidepressants to treat depressive symptoms and improve quality of life
      both prophylactically and after the onset of major depressive disorder. In
      addition, we detail a case report outlining the precipitous decline in health in
      1 patient with PC and depression.

PMID- 30199488
TI  - Metformin and Pancreatic Cancer Risk in Patients With Type 2 Diabetes.

PMID- 30199489
TI  - Patients With Pancreatic Ductal Adenocarcinoma Have High Serum Galectin-9 Levels:
      A Sweet Molecule to Keep an Eye On.

PMID- 30199490
TI  - Stabilized Incidence of Pediatric Acute Pancreatitis.

PMID- 30199491
TI  - Pancreatic Panniculitis: A Series of 4 Cases Associated With Pancreatic and
      Ampullary Disease.

PMID- 30199492
TI  - Islet Graft Function Is Preserved After Pregnancy in Patients With Previous Total
      Pancreatectomy With Islet Autotransplant.

PMID- 30199493
TI  - Cohort Study of Overutilization of Preventive Screening for Patients With
      Pancreatic Cancer.

PMID- 30199494
TI  - Abstracts and Highlight Papers of the 37th Annual European Society of Regional
      Anesthesia & Pain Therapy (ESRA) Congress 2018: Invited Speakers.

PMID- 30199495
TI  - Is There a Relationship Between Bone Quality and Hearing Level?
AB  - OBJECTIVES: This study evaluated the correlation between skull bone attenuation
      on temporal bone computed tomography (CT) and bone mineral density (BMD) of the
      central skeleton on dual-energy x-ray absorptiometry (DXA) and the correlation
      between bone quality and hearing level. STUDY DESIGN: Retrospective
      observational. SETTING: Tertiary referral center. PATIENTS/INTERVENTIONS: One
      hundred and one ears of 101 patients who underwent temporal bone CT and DXA with
      pure tone audiometry within 3 months of CT. MAIN OUTCOME MEASURES: Bone quality
      was measured by both bone attenuation of the clivus and petrous apex by setting a
      circular region of interest and by the cortical thickness of the occipital bone
      on CT. Partial correlation analysis was used to assess the correlation between
      bone quality around the skull on CT and BMD in the central skeleton after
      adjusting for age and sex. Partial correlations between pure tone audiometry and
      CT/DXA results were sought. RESULTS: There was no significant correlation between
      measurements on CT and BMD on DXA. The hearing level partially correlated with
      BMD on DXA. The average threshold of bone conduction showed a significant
      correlation with BMD at the femoral neck (correlation coefficient -0.241, p =
      0.020) and trochanter (correlation coefficient -0.244, p = 0.018), but there was
      no significant correlation between the average threshold of bone conduction and
      BMD at the lumbar spine (p = 0.177-0.332). CONCLUSION: We could not find a
      relationship between hearing loss and bone quality. Hearing levels can be
      affected by various factors, so further studies are needed to assess regional
      temporal bone quality.

PMID- 30199496
TI  - Cochlear Implantation With a Novel Long Straight Electrode: the Insertion Results
      Evaluated by Imaging and Histology in Human Temporal Bones.
AB  - HYPOTHESIS: To evaluate the insertion results of a novel straight array (EVO) by
      detailed imaging and subsequent histology in human temporal bones (TB).
      BACKGROUND: The main focuses of modern cochlear implant surgery are to prevent
      damage to the intracochlear structures and to preserve residual hearing. This is
      often achievable with new atraumatic electrode arrays in combination with
      meticulous surgical techniques. METHODS: Twenty fresh-frozen TBs were implanted
      with the EVO. Pre- and postoperative cone beam computed tomography scans were
      reconstructed and fused for an artifact-free representation of the electrode. The
      array's vertical position was quantified in relation to the basilar membrane on
      basis of which trauma was classified (Grades 0-4). The basilar membrane location
      was modeled from previous histologic data. The TBs underwent subsequent
      histologic examination. RESULTS: The EVOs were successfully inserted in all TBs.
      Atraumatic insertion (Grades 0-1) were accomplished in 14 of 20 TBs (70%). There
      were three apical translocations, and two basal translocations due to electrode
      bulging. One TB had multiple translocations. The sensitivity and specificity of
      imaging for detecting insertion trauma (Grades 2-4) was 87.5% and 97.3.0%,
      respectively. CONCLUSION: Comparable insertion results as reported for other
      arrays were also found for the EVO. Insertion trauma can be mostly avoided with
      meticulous insertion techniques to prevent bulging and by limiting the insertion
      depth angle to 360 degrees. The image fusion technique is a reliable tool for
      evaluating electrode placement and is feasible for trauma grading.

PMID- 30199497
TI  - What to Do When Cochlear Implant Users Plateau in Performance: a Pilot Study of
      Clinician-guided Aural Rehabilitation.
AB  - HYPOTHESIS: For experienced adult cochlear implant (CI) users who have reached a
      plateau in performance, a clinician-guided aural rehabilitation (CGAR) approach
      can improve speech recognition and hearing-related quality of life (QOL).
      BACKGROUND: A substantial number of CI users do not reach optimal performance in
      terms of speech recognition ability and/or personal communication goals. Although
      self-guided computerized auditory training programs have grown in popularity,
      compliance and efficacy for these programs are poor. We propose that CGAR can
      improve speech recognition and hearing-related QOL in experienced CI users.
      METHODS: Twelve adult CI users were enrolled in an 8-week CGAR program guided by
      a speech-language pathologist and audiologist. Nine patients completed the
      program along with pre-AR and immediate post-AR testing of speech recognition
      (AzBio sentences in quiet and in multitalker babble, Consonant-Nucleus-Consonant
      words in quiet), QOL (Nijmegen Cochlear Implant Questionnaire, Hearing Handicap
      Inventory for Adults/Elderly, and Speech, Spatial and Qualities of Hearing
      Scale), and neurocognitive functioning (working memory capacity, information
      processing speed, inhibitory control, speed of lexical/phonological access, and
      nonverbal reasoning). Pilot data for these nine patients are presented. RESULTS:
      From pre-CGAR to post-CGAR, group mean improvements in word recognition were
      found. Improvements were also demonstrated on some composite and subscale
      measures of QOL. Patients who demonstrated improvements in word recognition were
      those who performed most poorly at baseline. CONCLUSIONS: CGAR represents a
      potentially efficacious approach to improving speech recognition and QOL for
      experienced CI users. Limitations and considerations in implementing and studying
      aural rehabilitation approaches are discussed.

PMID- 30199498
TI  - Single Sided Deaf Cochlear Implant Users in the Difficult Listening Situation:
      Speech Perception and Subjective Benefit.
AB  - OBJECTIVES: Patients with single-sided deafness (SSD) have great difficulties in
      listening situations which rely on binaural auditory processing. The purpose of
      this study was to examine to which extent a cochlear implant (CI) can improve
      speech perception outcomes in various noisy listening environments. Additionally,
      the ability to use interaural level differences for sound localization and
      subjective benefit with the CI were assessed. METHODS: Ten single-sided deaf
      patients with CI were tested in different loudspeaker configurations with and
      without the CI. A multi-source noise field (MSNF) with uncorrelated noise from
      four different directions was used in addition to a setup with the signal from
      the CI side and noise from the normal-hearing side (SCINNH, azimuth of +/-45
      degrees). Ten normal-hearing subjects were used as a control for the setup.
      Speech understanding was measured by an adaptive sentence test (Oldenburg
      Sentence Test, OLSA) in stationary speech shaped noise and temporally modulated
      noise to assess the benefit in each listening situation. Sensitivity to
      interaural level differences was measured in a lateralization experiment.
      Furthermore, patients completed the Bern Benefit in Single-Sided Deafness (BBSS)
      questionnaire to assess subjective benefit with the CI. RESULTS: An overall
      average benefit in speech reception threshold (SRT) of 1.6 dB (+/-0.6 dB standard
      error of the mean [SEM]) was observed in the binaural listening condition (with
      CI) in all conditions. In the MSNF setup thresholds improved by 0.4 dB (+/-0.5 dB
      SEM) and in the SCINNH configuration by 2.7 dB (+/-0.7 dB SEM). The choice of
      masking noise effect also had a significant effect on the SRT outcome. The
      lateralization performance of the SSD users was on a par with the normal hearing
      group. BBSS scores reflect the overall benefit with the CI apparent in the speech
      test results. CONCLUSION: Patients with single-sided deafness do benefit from a
      CI in difficult listening environments and are able to localize sound based on
      interaural level differences. Considering these outcomes, cochlear implantation
      represents a promising treatment option for patients with single-sided deafness.

PMID- 30199499
TI  - Unilateral Versus Bilateral Cochlear Implantation in Children With Auditory
      Neuropathy Spectrum Disorder (ANSD).
AB  - OBJECTIVE: To evaluate audiologic outcomes following unilateral cochlear
      implantation with contralateral hearing aid (unilateral CI + HA) versus bilateral
      CI in children with auditory neuropathy spectrum disorder (ANSD). STUDY DESIGN:
      Retrospective case review. SETTING: Tertiary Care Otologic Practice. PATIENTS:
      Twenty-three patients with ANSD who underwent unilateral CI + HA or bilateral CI.
      INTERVENTIONS: Rehabilitative (CI). OUTCOME MEASURES: Speech perception scores
      and achievement of open-set speech. RESULTS: Preoperatively, all patients
      demonstrated lack of open-set speech perception with hearing aids (HAs) alone. Of
      the 23 patients included, 56.5% (n = 13) had developmental delay. Thirteen
      patients underwent unilateral CI + HA and 10 patients underwent bilateral CI. The
      median ages at CI activation were 3.3 and 2.0 years in the unilateral CI + HA and
      bilateral CI groups, respectively (p = 0.0688), with median lengths of CI use of
      45.9 and 47.2 months, respectively (p = 0.8438). The unilateral CI + HA and
      bilateral CI groups achieved open-set speech perception in 76.9% and 90.0% of
      cases, respectively (p = 0.6036), within median times of 19.5 and 28.0 months,
      respectively (p = 0.6334). Within the unilateral CI + HA group, the median aided
      PTAs in the contralateral ears of patients who did and did not achieve open-set
      speech were 57.5 dB HL (range, 42.5-91.7 dB HL) and 75.0 dB HL (range, 62.5-111.3
      dB HL) (p = 0.0455). CONCLUSIONS: Both bilateral CI and unilateral CI + HA groups
      achieved high rates of open-set speech perception. Bilateral CI may be beneficial
      in patients with bilateral hearing loss or those that fail to progress with
      unilateral CI + HA.

PMID- 30199500
TI  - Treatment of Ciprofloxacin-resistant Ear Infections.
AB  - OBJECTIVE: Ciprofloxacin resistance has been reported in 4.5% of patients with
      otorrhea and is increasing in prevalence. Due to ototoxicity, only
      fluoroquinolones are Food and Drug Administration approved for topical therapy in
      the middle ear. Furthermore, there is an assumption that antibiotic resistance is
      less relevant to topical therapy due to in vivo concentrations much higher than
      the minimum inhibitory concentration used to determine resistance. This study
      investigates ciprofloxacin-resistant infections and seeks to develop a better
      understanding of treatment options and outcomes. STUDY DESIGN: Retrospective
      review of 141 ciprofloxacin-resistant otologic infections. SETTING: Tertiary-care
      hospital. PATIENTS: Patients with culture-proven ciprofloxacin-resistant
      infections from 2008 to 2017. INTERVENTION(S): Antibiotic treatment with
      ciprofloxacin topical drops, ciprofloxacin plus oral antibiotics, and
      nonciprofloxacin therapy. MAIN OUTCOME MEASURE(S): Bacteriology for ciprofloxacin
      resistant infections and treatment effectiveness of various therapies. RESULTS:
      Methicillin-resistant Staphylococcus aureus (33%), Corynebacterium striatum
      (19%), and non-Methicillin-resistant Staphylococcus aureus (11%) are the most
      frequent causes of ciprofloxacin-resistant infections. Topical ciprofloxacin
      monotherapy was successful in 2.7% of infections compared with a 64.7% success
      rate with the addition of an oral antibiotic (p < 0.001). Nonciprofloxacin drops
      are more effective with a 70% cure rate compared with the 2.7% of the
      ciprofloxacin drops p < 0.001. There was no difference in treatment efficacy when
      comparing nonciprofloxacin topical therapy (70% cure) to nonciprofloxacin topical
      therapy plus oral antibiotic (83% cure, p = 0.17). CONCLUSIONS: Using
      ciprofloxacin drops to treat ciprofloxacin-resistant bacteria is ineffective and
      patients do significantly better with alternative therapy. This finding supports
      the conclusion that high concentrations achieved in topical applications are not
      sufficient to overcome antibiotic resistance.

PMID- 30199501
TI  - Superior Canal Dehiscence Involving the Superior Petrosal Sinus: A Novel
      Classification Scheme.
AB  - OBJECTIVES: To highlight superior semicircular canal dehiscence (SSCD) involving
      the superior petrosal sinus (SPS), and to propose a novel classification system
      for SPS associated SSCD with potential surgical implications. STUDY DESIGN:
      Multicenter retrospective review. SETTING: Three tertiary referral centers.
      PATIENTS: All patients diagnosed with SPS associated SSCD (1/2000 to 8/2016).
      Radiographic findings and clinical symptoms were analyzed. INTERVENTION: Surgical
      repair or observation. MAIN OUTCOME MEASURE: Radiographic findings and clinical
      symptoms were analyzed. RESULTS: Thirty-three dehiscences (30 patients) involving
      the SPS were identified. The average age at the time of presentation was 52.5
      years (median, 56.9; range, 4.9-75.3 yr), and 53.3% of patients were men. Three
      patients had bilateral SPS associated SSCD. The most common associated symptoms
      at presentation were episodic vertigo (63.6%), subjective hearing loss (60.6%),
      and aural fullness (57.6%). Four distinct types of dehiscence were identified:
      class Ia. SSCD involving a single dehiscence into an otherwise normal appearing
      SPS; class Ib. SSCD involving a single dehiscence into an apparent venous anomaly
      of the SPS; class IIa. SSCD involving two distinct dehiscences into the middle
      cranial fossa and the SPS; class IIb. SSCD involving a single confluent
      dehiscence into the middle cranial fossa and the SPS. CONCLUSIONS: SSCD involving
      the SPS represents a small but distinct subset of SSCD cases. This scenario can
      create a unique set of symptoms and surgical challenges when intervention is
      sought. Clinical findings and considerations for surgical intervention are
      provided to facilitate effective diagnosis and management.

PMID- 30199503
TI  - Factors That Affect Length of Hospital Stay After Vestibular Schwannoma Surgery.
AB  - OBJECTIVE: To identify perioperative factors that influence hospital length of
      stay (LOS) after resection of vestibular schwannoma (VS). STUDY DESIGN:
      Retrospective case review. SETTING: Tertiary skull base referral center.
      PATIENTS: Patients who underwent acoustic neuroma resection between January 1,
      2007 and January 1, 2014. INTERVENTIONS: Approaches used for VS resection
      included translabyrinthine and retrosigmoid. MAIN OUTCOME MEASURES: LOS and
      several perioperative factors that may delay hospital discharge were examined.
      Factors included were patient demographics (age and sex), tumor characteristics
      (size), surgical factors (operative time, approach, revision surgery, date of
      surgery), and immediate postoperative factors (presence of vertigo or immediate
      postoperative complications). RESULTS: Two hundred eighty-eight patients
      underwent VS resection during the study period. Two hundred fifty-five patients
      had complete charts available for review. LOS ranged from 1 to 10 days with an
      average of 2.66 days and mode of 2 days. One hundred thirty-one patients were
      admitted for <=2 days and 124 patients stayed longer. Of the perioperative
      factors examined with univariate analysis, female gender (p = 0.0266) and
      presence of postoperative vertigo (p < 0.0001) were statistically significant
      factors associated with LOS >2 days. On multivariate logistic regression analysis
      with odds ratios (OR), older patient age (OR = 1.028, p = 0.0177), female gender
      (OR = 1.810, p = 0.0314), longer operative time (OR = 1.424, p = 0.0007), and
      presence of postoperative vertigo (OR = 4.904, p < 0.0001) carried a
      statistically significant increased odds toward a LOS >2 days. CONCLUSIONS: VS
      surgery and postoperative care can be carried out efficiently with a minimal LOS.
      Identifying factors that may prolong LOS may help the operative team anticipate
      and address needs to optimize LOS.

PMID- 30199504
TI  - Imaging Case of the Month: Cystic Facial Nerve Schwannoma.

PMID- 30199502
TI  - A Polymer-Based Extended Release System for Stable, Long-term Intracochlear Drug
      Delivery.
AB  - OBJECTIVE: Investigate a new polymer-based drug coating suitability for safe
      intracochlear delivery and ability to maintain long-term physiologically active
      levels of the corticosteroid fluticasone propionate. STUDY DESIGN: In vitro
      dissolution study to evaluate release profiles of polymer-coated drug particles
      and in vivo studies using a guinea pig model to measure perilymph drug
      concentrations at specific time points after implantation with polymer-coated
      drug particles and evaluate their effect on hearing function. METHODS: Polymer
      coated fluticasone propionate (FP) particles were surgically implanted in guinea
      pigs through the round window membrane into the cochlear scala tympani. In the
      pilot study, pre- and post-op hearing thresholds were conducted on days 7, 14,
      and 42. In a second study, post-op hearing thresholds were conducted on days 90,
      120, and 180. Perilymph drug concentrations were measured on the same time
      points. RESULTS: In 15 of 16 animals from day 7 through day 90, drug levels were
      within the targeted range, with no initial burst release detected. Drug was
      present in all animals on day 90 and was detected in some animals at 120 and 180
      days. Hearing was tested and compared with non-implanted ears. Very good hearing
      preservation was observed in ears implanted with intracochlear particles when
      compared with contralateral ears. CONCLUSIONS: The polymer-based extended release
      system is effective in providing long-term, stable drug delivery for at least 90
      days with good hearing outcomes. The results of this study support the potential
      for achieving long-term drug delivery with a single intracochlear administration.

PMID- 30199505
TI  - Cerebellar Abscess Caused by Extension of an Otogenic Infection Through the
      Labyrinth and Internal Auditory Canal.

PMID- 30199506
TI  - Giant Osteoma in the Mastoid of the Temporal Bone: Complete Excision of a Rare
      Tumor.

PMID- 30199507
TI  - Leber Hereditary Optic Neuropathy in a Mother and Daughter Associated With
      m.10197G>A Mutation.

PMID- 30199508
TI  - Anti-Interleukin-6 Antibody as Treatment for Giant Cell Arteritis.

PMID- 30199509
TI  - IL-6 Blockade and its Therapeutic Success in Giant Cell Arteritis.

PMID- 30199510
TI  - Monitoring of Conjunctival Microcirculation Reflects Sublingual Microcirculation
      in Ovine Septic and Hemorrhagic Shock.
AB  - INTRODUCTION: The conjunctival region may serve as an alternative site for
      microcirculatory measurements. The present study was performed to investigate the
      correlation of sublingual and conjunctival microcirculation in ovine models of
      septic and hemorrhagic shock. METHODS: Septic shock was induced in ten sheep by
      inoculation of feces into the peritoneal cavity until mean arterial pressure
      (MAP) was <60 mmHg and arterial lactate level was >=1.8 mmol L. In another ten
      sheep, hemorrhagic shock was induced by stepwise blood withdrawal of 3x10 mL kg.
      Systemic hemodynamics and parameters of blood gas analysis were analyzed.
      Conjunctival and sublingual microcirculation were monitored and analyzed
      according to current recommendations. Parameters were measured at baseline and at
      shock time. RESULTS: Septic shock resulted in a significant drop in MAP and
      cardiac index (CI), and an increase in arterial lactate levels. While the total
      vessel density (TVD) in the sublingual microcirculation was relatively well
      maintained, the perfused vessel density (PVD) and the microvascular flow index
      (MFI) were significantly reduced in septic shock. Hemorrhagic shock reduced MAP
      and CI, and increased arterial lactate levels. TVD was relatively unchanged in
      hemorrhagic shock, while PVD and MFI were significantly decreased. The
      conjunctival microcirculation showed similar changes to the sublingual
      microcirculation in both models. CONCLUSIONS: The findings of the current study
      support the proposed use of the conjunctiva as an alternative site for
      microcirculatory monitoring in hemorrhagic and septic shock. Further studies
      should focus on the impact of therapy and the loss of correlation between the
      different microcirculatory regions in advanced shock.

PMID- 30199511
TI  - Safety of Tranexamic Acid During Pediatric Trauma: A Nationwide Database Study.
AB  - OBJECTIVES: The present study aimed to examine the association between tranexamic
      acid use and adverse effects (seizures, thromboembolism, and renal dysfunction)
      in a pediatric trauma population using a national inpatient database in Japan. We
      also assessed the association between tranexamic acid use and in-hospital
      mortality. DESIGN: A nationwide, retrospective cohort study using propensity
      score analyses. SETTING: Japanese Diagnosis Procedure Combination inpatient
      database. PATIENTS: Pediatric patients less than or equal to 12 years old
      admitted in hospital with the diagnosis of trauma between July 2010 and March
      2014 (n = 61,779). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Propensity
      score matching created 1,914 pairs of patients with and without tranexamic acid
      administration. Propensity-matched analysis showed that the proportion of
      seizures was significantly higher in the tranexamic acid group than in the
      nontranexamic acid group (7/1,914, 0.37% vs 0/1,914, 0%; difference, 0.37%; 95%
      CI, 0.10-0.64; p = 0.008). However, none of the other outcomes were significantly
      different between the groups. CONCLUSIONS: Tranexamic acid use is associated with
      a significantly increased risk of seizures. However, no difference exists among
      any other outcomes between the tranexamic acid and nontranexamic acid groups.

PMID- 30199513
TI  - Transcranial Direct-Current Stimulation on Motor Function in Pediatric Cerebral
      Palsy: A Systematic Review.
AB  - PURPOSE: To determine effects of transcranial direct-current stimulation (tDCS)
      on motor function for children with cerebral palsy. METHODS: Six electronic
      databases were searched using terms related to tDCS, combined with functional
      deficits/associated clinical measures. Results were filtered, including
      randomized controlled trials in English and children with cerebral palsy. Data
      were extracted using standardized procedures, and the PEDro scale was used to
      assess quality and meta-analyses conducted. RESULTS: From 135 articles, 9 studies
      with moderate quality met inclusion criteria. Six were included in 7 separate
      meta-analyses supporting a benefit of tDCS for static balance, only at follow-up.
      Benefits of tDCS on dynamic balance, step length, and mobility were not
      established. CONCLUSIONS: The findings from meta-analyses suggest that tDCS may
      provide improvements in static balance at follow-up in children with cerebral
      palsy and positive effects on gait velocity; however, there was heterogeneity.
      Further research is needed before this therapy can be endorsed.

PMID- 30199512
TI  - Long-Term Safety and Efficacy of Minimally Invasive Lumbar Decompression
      Procedure for the Treatment of Lumbar Spinal Stenosis With Neurogenic
      Claudication: 2-Year Results of MiDAS ENCORE.
AB  - BACKGROUND AND OBJECTIVES: This study evaluated the long-term durability of the
      minimally invasive lumbar decompression (MILD) procedure in terms of functional
      improvement and pain reduction for patients with lumbar spinal stenosis and
      neurogenic claudication due to hypertrophic ligamentum flavum. This is a report
      of 2-year follow-up for MILD study patients. METHODS: This prospective,
      multicenter, randomized controlled clinical study compared outcomes for 143
      patients treated with MILD versus 131 treated with epidural steroid injections.
      Follow-up occurred at 6 months and at 1 year for the randomized phase and at 2
      years for MILD subjects only. Oswestry Disability Index, Numeric Pain Rating
      Scale, and Zurich Claudication Questionnaire were used to evaluate function and
      pain. Safety was evaluated by assessing incidence of device-/procedure-related
      adverse events. RESULTS: All outcome measures demonstrated clinically meaningful
      and statistically significant improvement from baseline through 6-month, 1-year,
      and 2-year follow-ups. At 2 years, Oswestry Disability Index improved by 22.7
      points, Numeric Pain Rating Scale improved by 3.6 points, and Zurich Claudication
      Questionnaire symptom severity and physical function domains improved by 1.0 and
      0.8 points, respectively. There were no serious device-/procedure-related adverse
      events, and 1.3% experienced a device-/procedure-related adverse event.
      CONCLUSIONS: MILD showed excellent long-term durability, and there was no
      evidence of spinal instability through 2-year follow-up. Reoperation and spinal
      fracture rates are lower, and safety is higher for MILD versus other lumbar spine
      interventions, including interspinous spacers, surgical decompression, and spinal
      fusion. Given the minimally invasive nature of this procedure, its robust success
      rate, and durability of outcomes, MILD is an excellent choice for first-line
      therapy for select patients with central spinal stenosis suffering from
      neurogenic claudication symptoms with hypertrophic ligamentum flavum. CLINICAL
      TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov, identifier
      NCT02093520.

PMID- 30199514
TI  - Physical Therapist Coaching to Improve Physical Activity in Children With Brain
      Tumors: A Pilot Study.
AB  - PURPOSE: Children with brain tumors (BTs) experience fatigue and decreased
      quality of life (QOL). Physical activity (PA) is recommended during and after
      cancer treatment. We explored whether a fitness tracker intervention combined
      with tailored coaching by a physical therapist (PT) increased PA and QOL and
      decreased fatigue in children with BTs. METHODS: Participants were 7 to 18 years'
      old, within 2 years of diagnosis, and received a 12-week PA intervention using a
      fitness tracker combined with 5 PT coaching sessions. Steps/day measured by
      Fitbit and self-reports of QOL, fatigue, and PA were evaluated at baseline, 12
      weeks, and 24 weeks. RESULTS: Participants had nonsignificant increase in
      steps/day. Total fatigue, general, and sleep/rest subscales improved while
      cognitive fatigue and QOL remained unchanged. Higher steps/day were associated
      with lower fatigue. CONCLUSION: This is a feasible intervention that may
      contribute to an increase in PA and improve fatigue in children with BTs.

PMID- 30199515
TI  - Effects of a Gaming Platform on Balance Training for Children With Cerebral
      Palsy.
AB  - PURPOSE: A platform requiring multidimensional trunk movement facilitated
      postural balance in children with cerebral palsy. METHODS: The intervention group
      (n = 20) received 12 weeks of playing personal computer (PC) games using the
      platform, and the control group (n = 20) played the same games using a computer
      mouse. Outcomes were center-of-pressure sway, the Berg Balance Scale (BBS),
      Fullerton Advanced Balance Scale (FAB), and Timed Up and Go (TUG) test scores.
      RESULTS: There were significant interactions between groups and time. There was a
      significant between-group difference in center-of-pressure sway excursion, BBS
      test, and TUG test over time. Participants in the intervention group had better
      balance performance compared with the control group. CONCLUSION: Balance training
      using a PC gaming platform may improve exercise compliance and enhance recovery
      of balance in children with cerebral palsy.

PMID- 30199516
TI  - Adapted Motivational Interviewing to Promote Exercise in Adolescents With
      Congenital Heart Disease: A Pilot Trial.
AB  - PURPOSE: To assess a motivational interviewing (MI) intervention to improve
      moderate-to-vigorous physical activity (MVPA) in adolescents with congenital
      heart disease. METHODS: Intervention participants received one-on-one telephone
      based adapted MI sessions over 3 months. Outcomes were acceptability, change
      mechanisms (stage of change and self-efficacy), and limited efficacy (physical
      activity, fitness, and quality of life). RESULTS: Thirty-six participants were
      randomized. Intervention participants completed 4.2 +/- 1.2/6 MI sessions, with
      no improvements in the high self-efficacy or stage of change observed.
      Participants accumulated 47.24 +/- 16.36 minutes of MVPA/day, and had comparable
      outcomes to peers without heart disease (except for functional capacity). There
      was no significant difference in change in any outcome by group. CONCLUSIONS: The
      intervention was acceptable, but effectiveness could not be determined due to the
      nature and size of sample. CLINICAL RELEVANCE: Pediatric cardiac rehabilitation
      remains the sole effective intervention to increase MVPA in this population.

PMID- 30199517
TI  - Is This Study a Clinical Trial? Why Does It Matter?

PMID- 30199518
TI  - Experience of Robotic Exoskeleton Use at Four Spinal Cord Injury Model Systems
      Centers.
AB  - BACKGROUND AND PURPOSE: Refinement of robotic exoskeletons for overground walking
      is progressing rapidly. We describe clinicians' experiences, evaluations, and
      training strategies using robotic exoskeletons in spinal cord injury
      rehabilitation and wellness settings and describe clinicians' perceptions of
      exoskeleton benefits and risks and developments that would enhance utility.
      METHODS: We convened focus groups at 4 spinal cord injury model system centers. A
      court reporter took verbatim notes and provided a transcript. Research staff used
      a thematic coding approach to summarize discussions. RESULTS: Thirty clinicians
      participated in focus groups. They reported using exoskeletons primarily in
      outpatient and wellness settings; 1 center used exoskeletons during inpatient
      rehabilitation. A typical episode of outpatient exoskeleton therapy comprises 20
      to 30 sessions and at least 2 staff members are involved in each session.
      Treatment focuses on standing, stepping, and gait training; therapists measure
      progress with standardized assessments. Beyond improved gait, participants
      attributed physiological, psychological, and social benefits to exoskeleton use.
      Potential risks included falls, skin irritation, and disappointed expectations.
      Participants identified enhancements that would be of value including greater
      durability and adjustability, lighter weight, 1-hand controls, ability to
      navigate stairs and uneven surfaces, and ability to balance without upper
      extremity support. DISCUSSION AND CONCLUSIONS: Each spinal cord injury model
      system center had shared and distinct practices in terms of how it integrates
      robotic exoskeletons into physical therapy services. There is currently little
      evidence to guide integration of exoskeletons into rehabilitation therapy
      services and a pressing need to generate evidence to guide practice and to inform
      patients' expectations as more devices enter the market.Video Abstract available
      for more insights from the authors (see Video, Supplemental Digital Content 1,
      available at: http://links.lww.com/JNPT/A231).

PMID- 30199519
TI  - Neuro-ophthalmic complications of IgG4-related disease.
AB  - PURPOSE OF REVIEW: IgG4-related disease (IgG4-RD) is increasingly recognized as a
      fibroinflammatory disease with a plethora of organ-specific manifestations but a
      particular predilection for head and neck tissues, including the nervous system.
      This review discusses general features and organ-specific presentations of IgG4
      RD as well as treatment considerations, particularly emphasizing features of
      neuro-ophthalmic interest. RECENT FINDINGS: IgG4-RD is emerging as a common cause
      of several fibroinflammatory disorders in the head and neck that were previously
      considered idiopathic, such as sclerosing orbital pseudotumor, orbital myositis,
      hypophysitis, and hypertrophic pachymeningitis. New and unusual presentations
      continue to be described, including a number of vascular manifestations.
      Substantial progress has been made in elucidating the cell types involved in IgG4
      RD, and new pathogenic models are being proposed. Although clinicopathologic
      correlation remains the cornerstone of diagnosis, ancillary tests such as flow
      cytometry for circulating plasmablasts and PET-computed tomography have high
      sensitivity, and certain radiologic features are recognized to be particularly
      suggestive, such as infraorbital nerve enlargement in IgG4-RD orbitopathy. IgG4
      RD often responds to steroids but incomplete responses and relapses are common.
      Rituximab is emerging as a promising new therapy. SUMMARY: The current review
      summarizes manifestations of IgG4RD that are of particular relevance to neuro
      ophthalmic practice.

PMID- 30199520
TI  - Concurrent Detection of Bacterial Pathogens in Hospital Roommates.
AB  - BACKGROUND: Some nurse-driven interventions have successfully reduced rates of
      healthcare-associated infections (HAI), though incidence remains unacceptably
      high. Bacterial contamination in patient rooms may be a source of exposure for
      patients and, thus, a target for future interventions; however, few studies have
      investigated the role of the patient room on organism acquisition. OBJECTIVES:
      The purpose of this study was to determine the incidence of concurrent detection
      of bacterial pathogens among patients sharing a hospital room. METHODS: We
      performed a retrospective network analysis using electronic administrative and
      clinical data collected from all patients admitted in 2006 through 2012 to four
      New York City hospitals totaling 2,065 beds within 183 inpatient units. A
      computerized algorithm identified concurrent organism detection among roommates,
      defined as two patients who shared a room on at least one day and had a first
      positive culture for the same organism within three days following cohabitation.
      RESULTS: In total, 741,271 patient admissions were included. The algorithm
      identified 373 concurrent detection events: 158 (42%) in which the patients'
      first positive cultures were drawn after they were no longer sharing a room but
      within three days of cohabitation; 144 (39%) in which the patients' first
      positive cultures were drawn while they were still sharing a room but on
      different days; and 71 (19%) in which the patients' first positive cultures were
      drawn while they were sharing a room on the same day.DiscussionMethods to improve
      environmental decontamination should be included as part of a comprehensive
      approach to infection prevention in hospitals. Nurses have an important role to
      play in the planning and implementation of interventions to reduce bioburden in
      the patient environment.

PMID- 30199521
TI  - Scientists Wanted!

PMID- 30199522
TI  - The Effects of Dracocephalum Heterophyllum Benth Flavonoid on Hypertrophic
      Cardiomyocytes Induced by Angiotensin II in Rats.
AB  - BACKGROUND Dracocephalum heterophyllum Benth flavonoid (DHBF) is a Tibetan and
      Uighur traditional medicine used to treat various disorders such as hypertension,
      lung heat, cough, and bronchitis; it has good antioxidant activity. Previous
      studies have shown that DHBF can reduce blood pressure in renovascular
      hypertensive rats, improve left ventricular systolic and diastolic function, and
      improve myocardial contractility. Therefore, we aimed to study the effect of DHBF
      on cardiomyocyte hypertrophy in cultured cells. MATERIAL AND METHODS Neonatal rat
      cardiomyocytes were cultured, and hypertrophy was induced by angiotensin II (Ang
      II), with or without varying concentrations of the DHBF extract. Cell Counting
      Kit-8 assay was used to assess cell viability, RT-qPCR was used to determine mRNA
      levels, confocal laser scanning microscopy was used to measure cell surface area
      and intracellular Ca2+ concentrations ([Ca2+]i), and colorimetric assays were
      used to assess nitric oxide (NO) levels and nitric oxide synthase (NOS) activity.
      RESULTS Ang II treatment of cardiomyocytes reduced cell viability to ~75% that of
      controls. Ang II treatment also increased cell surface area; increased mRNA
      expression of c-jun, atrial natriuretic peptide (ANP), brain natriuretic peptide
      (BNP), and beta-myosin heavy chain (beta-MHC); increased [Ca2+]i; and reduced NOS
      activity and NO production. DHBF treatment could reverse these effects in a
      concentration-dependent manner. CONCLUSIONS These results showed that DHBF can
      ameliorate cardiomyocyte hypertrophy induced by Ang II, as indicated by the
      downregulation of cardiac hypertrophy genes (ANP, BNP, and beta-MHC) and
      reduction in cell surface area. The mechanism may be related to NO release and
      [Ca2+]I regulation.

PMID- 30199523
TI  - Within-quadrant position and orientation specificity after extensive orientation
      discrimination learning is related to performance gains during late learning.
AB  - The last decade has seen the emergence of new views about the mechanisms
      underlying specificity (or, conversely, generalization) of visual skill learning.
      Here, we trained participants at orientation discrimination paradigm at a
      peripheral position to induce position and orientation specificity and to test
      its underlying mechanisms. Specifically, we aimed to test whether the within
      quadrant spatial gradient of generalization is determined by cortical
      magnification, which would show that retinotopic plasticity contributes to
      learning and specificity. Additionally, we aimed to test whether late parts of
      the learning relate differently to specificity compared to early parts. This is
      relevant in the context of double training papers, which suggest that rule-based
      mechanisms of specificity in fast, early learning also would apply to late,
      slower learning. Our data showed partial but significant position and orientation
      specificity within quadrants. Interestingly, specificity was greatest for those
      participants who had continued to show threshold decreases during the last five
      sessions of training (late, asymptotic learning). Performance gains during early
      learning were less related to specificity. A trend for skill to spread over
      larger distances towards periphery than towards central vision suggested
      contributions to transfer of early visual areas showing cortical magnification of
      central vision. Control experiments however did not support this hypothesis. In
      summary, our study demonstrates significant specificity after extensive
      perceptual learning, and indicates that asymptotic learning recruits specific
      mechanisms that promote specificity, and that may not be recruited yet in early
      parts of the learning. The contributions of different mechanisms to early and
      late learning suggests that following these different learning periods,
      generalization relies on different principles and is subjected to different
      limits.

PMID- 30199524
TI  - Quantification by SIFT-MS of volatile compounds produced by the action of sodium
      hypochlorite on a model system of infected root canal content.
AB  - Root canal irrigation with sodium hypochlorite (NaOCl) is an indispensable part
      of the chemomechanical preparation of infected root canals in Endodontology.
      However, there is limited information on the emergence of toxic or hazardous
      volatile compounds (VOCs) from the interaction of NaOCl with the infected content
      of tooth biomaterials. The aim of this study was to assess the formation of VOCs
      and disinfection by-products (DBPs) following the interaction of NaOCl 2.5% v/v
      with a model system of different sources of natural organic matter (NOM) present
      in infected root canals, including dentine powder, planktonic multi-microbial
      suspensions (Propionibacterium acnes, Staphylococcus epidermidis, Actinomyces
      radicidentis, Streptococcus mitis and Enterococcus faecalis strain OMGS3202),
      bovine serum albumin 4%w/v and their combination. NaOCl was obtained from a stock
      solution with iodometric titration. Ultrapure water served as negative control.
      Samples were stirred at 37 degrees C in aerobic and anaerobic conditions for
      30min to approximate a clinically realistic time. Centrifugation was performed
      and the supernatants were collected and stored at -800 C until analysis. The
      reaction products were analysed in real time by selected ion flow tube mass
      spectrometry (SIFT-MS) in triplicates. SIFT-MS analysis showed that the released
      VOCs included chlorinated hydrocarbons, particularly chloroform, together with
      unexpected higher levels of some nitrogenous compounds, especially acetonitrile.
      No difference was observed between aerobic and anaerobic conditions. The chemical
      interaction of NaOCl with NOM resulted in the formation of toxic chlorinated VOCs
      and DBPs. SIFT-MS analysis proved to be an effective analytical method. The risks
      from the rise of toxic compounds require further consideration in dentistry.

PMID- 30199526
TI  - Comparison of individual and pooled diagnostic examination strategies during the
      national mapping of soil-transmitted helminths and Schistosoma mansoni in
      Ethiopia.
AB  - BACKGROUND: Laboratory-based studies have highlighted that pooling stool and
      urine samples can reduce costs and diagnostic burden without a negative impact on
      the ability to estimate the intensity of soil-transmitted helminth (STH, Ascaris
      lumbricoides, Trichuris trichiura and hookworms) and schistosome infections
      (Schistosoma mansoni and S. haematobium). In this study, we compare individual
      and pooled stool examination strategies in a programmatic setting. METHODS: Stool
      samples were collected from 2,650 children in 53 primary schools in Amhara
      Regional State, Ethiopia, during the national mapping of STHs and schistosome
      infections. Eggs of STHs and S. mansoni were quantified in both individual and
      pooled samples (pools were made from 10 individual samples) using a single Kato
      Katz smear. PRINCIPAL FINDINGS: A pooled diagnostic examination strategy provided
      comparable estimates of infection intensity with higher fecal egg count
      (expressed in eggs per gram of stool (EPG)) than those based on individual
      strategy (Ascaris: 45.1 EPG vs. 93.9, p = 0.03; Trichuris: 1.8 EPG vs. 2.1 EPG, p
      = 0.95; hookworms: 17.5 EPG vs. 28.5 EPG, p = 0.18; S. mansoni: 1.6 EPG vs. 3.4
      EPG, p = 0.02), but had lower sensitivity (Ascaris: 90.0% vs. 55.0%; Trichuris:
      91.7% vs. 16.7%; hookworms: 92.6% vs. 61.8%; S. mansoni: 100% vs. 51.7%, p <
      0.001). A pooled approach resulted in a ~70% reduction in time required for
      sample testing, but reduced total operational costs by only ~11%.
      CONCLUSIONS/SIGNIFICANCE: A pooled approach holds promise for the rapid
      assessment of intensity of helminth infections in a programmatic setting, but it
      is not major cost-saving strategy. Further investigation is required to determine
      when and how pooling can be utilized. Such work should also include validation of
      statistical methods to estimate prevalence based on pooling samples. Finally, the
      comparison of operational costs across different scenarios of national program
      management will help determine whether pooling is indeed worthwhile considering.

PMID- 30199525
TI  - Assessment of mutation probabilities of KRAS G12 missense mutants and their long
      timescale dynamics by atomistic molecular simulations and Markov state modeling.
AB  - A mutated KRAS protein is frequently observed in human cancers. Traditionally,
      the oncogenic properties of KRAS missense mutants at position 12 (G12X) have been
      considered as equal. Here, by assessing the probabilities of occurrence of all
      KRAS G12X mutations and KRAS dynamics we show that this assumption does not hold
      true. Instead, our findings revealed an outstanding mutational bias. We conducted
      a thorough mutational analysis of KRAS G12X mutations and assessed to what extent
      the observed mutation frequencies follow a random distribution. Unique tissue
      specific frequencies are displayed with specific mutations, especially with G12R,
      which cannot be explained by random probabilities. To clarify the underlying
      causes for the nonrandom probabilities, we conducted extensive atomistic
      molecular dynamics simulations (170 MUs) to study the differences of G12X
      mutations on a molecular level. The simulations revealed an allosteric
      hydrophobic signaling network in KRAS, and that protein dynamics is altered among
      the G12X mutants and as such differs from the wild-type and is mutation-specific.
      The shift in long-timescale conformational dynamics was confirmed with Markov
      state modeling. A G12X mutation was found to modify KRAS dynamics in an
      allosteric way, which is especially manifested in the switch regions that are
      responsible for the effector protein binding. The findings provide a basis to
      understand better the oncogenic properties of KRAS G12X mutants and the
      consequences of the observed nonrandom frequencies of specific G12X mutations.

PMID- 30199528
TI  - Propagation of cell death in dropdead1, a sorghum ortholog of the maize lls1
      mutant.
AB  - We describe dropdead1-1 (ded1), an EMS-induced recessive lesion mimic mutant of
      sorghum. It is characterized by the formation of spreading necrotic lesions that
      share many attributes with those associated with the maize lethal leaf spot1
      (lls1) and Arabidopsis accelerated cell death1 (acd1) mutation. We show that as
      in lls1, ded1 lesions are initiated by wounding and require light for continued
      propagation, and that loss of chloroplast integrity is responsible for ded1 cell
      death. Consistent with these parallels, we demonstrate that ded1 is an ortholog
      of lls1 and encodes pheophorbide a oxidase (PaO) with 93% identity at the protein
      level. The mutant ded1 allele resulted from a stop codon-inducing single base
      pair change in exon 6 of the sorghum ortholog of lls1. The ded1 transcript was
      rapidly and transiently induced after wounding and substantially elevated in
      leaves containing ded1 lesions. Given that PaO is a key enzyme of the chlorophyll
      degradation pathway, its dysfunction would result in the accumulation of
      pheophorbide, a potent photosensitizer that results in the production of singlet
      oxygen. Consistent with this, cell death associated with ded1 lesions is most
      likely caused by singlet oxygen as our results exclude superoxide and H2O2 from
      this role. We explore the signal responsible for the propagation of lesions
      affecting both ded1 and lls1 lesions and find that both developmental age and
      ethylene increase the rate of lesion expansion in both mutants.

PMID- 30199527
TI  - MiR-202 controls female fecundity by regulating medaka oogenesis.
AB  - Female gamete production relies on coordinated molecular and cellular processes
      that occur in the ovary throughout oogenesis. In fish, as in other vertebrates,
      these processes have been extensively studied both in terms of
      endocrine/paracrine regulation and protein expression and activity. The role of
      small non-coding RNAs in the regulation of animal reproduction remains however
      largely unknown and poorly investigated, despite a growing interest for the
      importance of miRNAs in a wide variety of biological processes. Here, we analyzed
      the role of miR-202, a miRNA predominantly expressed in male and female gonads in
      several vertebrate species. We studied its expression in the medaka ovary and
      generated a mutant line (using CRISPR/Cas9 genome editing) to determine its
      importance for reproductive success with special interest for egg production. Our
      results show that miR-202-5p is the most abundant mature form of the miRNA and
      that it is expressed in granulosa cells and in the unfertilized egg. The knock
      out (KO) of mir-202 gene resulted in a strong phenotype both in terms of number
      and quality of eggs produced. Mutant females exhibited either no egg production
      or produced a dramatically reduced number of eggs that could not be fertilized,
      ultimately leading to no reproductive success. We quantified the size
      distribution of the oocytes in the ovary of KO females and performed a large
      scale transcriptomic analysis approach to identified dysregulated molecular
      pathways. Together, cellular and molecular analyses indicate that the lack of miR
      202 impairs the early steps of oogenesis/folliculogenesis and decreases the
      number of large (i.e. vitellogenic) follicles, ultimately leading to dramatically
      reduced female fecundity. This study sheds new light on the regulatory mechanisms
      that control the early steps of follicular development, including possible
      targets of miR-202-5p, and provides the first in vivo functional evidence that a
      gonad-predominant microRNA may have a major role in female reproduction.

PMID- 30199529
TI  - Implications of alternative routes to APC/C inhibition by the mitotic checkpoint
      complex.
AB  - The mitotic checkpoint (also called spindle assembly checkpoint) is a signaling
      pathway that ensures faithful chromosome segregation. Mitotic checkpoint proteins
      inhibit the anaphase-promoting complex (APC/C) and its activator Cdc20 to prevent
      precocious anaphase. Checkpoint signaling leads to a complex of APC/C, Cdc20, and
      checkpoint proteins, in which the APC/C is inactive. In principle, this final
      product of the mitotic checkpoint can be obtained via different pathways, whose
      relevance still needs to be fully ascertained experimentally. Here, we use
      mathematical models to compare the implications on checkpoint response of the
      possible pathways leading to APC/C inhibition. We identify a previously
      unrecognized funneling effect for Cdc20, which favors Cdc20 incorporation into
      the inhibitory complex and therefore promotes checkpoint activity. Furthermore,
      we find that the presence or absence of one specific assembly reaction determines
      whether the checkpoint remains functional at elevated levels of Cdc20, which can
      occur in cancer cells. Our results reveal the inhibitory logics behind checkpoint
      activity, predict checkpoint efficiency in perturbed situations, and could inform
      molecular strategies to treat malignancies that exhibit Cdc20 overexpression.

PMID- 30199530
TI  - Copper-dependent amino oxidase 3 governs selection of metabolic fuels in
      adipocytes.
AB  - Copper (Cu) has emerged as an important modifier of body lipid metabolism.
      However, how Cu contributes to the physiology of fat cells remains largely
      unknown. We found that adipocytes require Cu to establish a balance between main
      metabolic fuels. Differentiating adipocytes increase their Cu uptake along with
      the ATP7A-dependent transport of Cu into the secretory pathway to activate a
      highly up-regulated amino-oxidase copper-containing 3 (AOC3)/semicarbazide
      sensitive amine oxidase (SSAO); in vivo, the activity of SSAO depends on the
      organism's Cu status. Activated SSAO oppositely regulates uptake of glucose and
      long-chain fatty acids and remodels the cellular proteome to coordinate changes
      in fuel availability and related downstream processes, such as glycolysis, de
      novo lipogenesis, and sphingomyelin/ceramide synthesis. The loss of SSAO
      dependent regulation due to Cu deficiency, limited Cu transport to the secretory
      pathway, or SSAO inactivation shifts metabolism towards lipid-dependent pathways
      and results in adipocyte hypertrophy and fat accumulation. The results establish
      a role for Cu homeostasis in adipocyte metabolism and identify SSAO as a
      regulator of energy utilization processes in adipocytes.

PMID- 30199531
TI  - "My wife's mistrust. That's the saddest part of being a diabetic": A qualitative
      study of sexual well-being in men with Type 2 diabetes in sub-Saharan Africa.
AB  - INTRODUCTION: Sexual dysfunction is a common complication for men with diabetes,
      yet little is known about the lived experiences of sexual difficulties within the
      context of diabetes, particularly in low-and-middle-income countries. This study
      explores how men with type 2 diabetes in three sub-Saharan African settings (Cape
      Town and Johannesburg, South Africa; Lilongwe, Malawi) perceive and experience
      sexual functioning and sexual well-being, and the biopsychosocial contexts in
      which these occur and are shaped. METHODS: We used a qualitative research design,
      including individual interviews (n = 15) and focus group discussions (n = 4).
      Forty-seven men were included in the study. We used an inductive thematic
      analysis approach to develop our findings. A biopsychosocial conceptual model on
      the relationship between chronic illness and sexuality informed the
      interpretation of findings. RESULTS: Men across the study settings identified
      sexual difficulties as a central concern of living with diabetes. These
      difficulties went beyond biomedical issues of erectile dysfunction, comprising
      complex psychological and relational effects. Low self-esteem, related to a sense
      of loss of masculinity and reduced sexual and emotional intimacy in partner
      relationships were common experiences. Specific negative relational effects
      included suspicion of infidelity, mutual mistrust, general unhappiness, and fear
      of losing support from partners. These effects may impact on men's ability to
      cope with their diabetes. Further stressors were a lack of information about the
      reasons for their sexual difficulties, perceived lack of support from healthcare
      providers and an inability to communicate with partners about sexual
      difficulties. CONCLUSION: More in-depth research is needed to better understand
      sexual functioning and well-being within the context of diabetes, and its
      potential impact on diabetes self-management. Holistic and patient-centered care
      should include raising awareness of sexual problems as a potential complication
      of diabetes amongst patients, their partners and care providers, and
      incorporating sexual well-being as part of routine clinical care.

PMID- 30199532
TI  - Transcriptional outcomes and kinetic patterning of gene expression in response to
      NF-kappaB activation.
AB  - Transcription factor nuclear factor kappa B (NF-kappaB) regulates cellular
      responses to environmental cues. Many stimuli induce NF-kappaB transiently,
      making time-dependent transcriptional outputs a fundamental feature of NF-kappaB
      activation. Here we show that NF-kappaB target genes have distinct kinetic
      patterns in activated B lymphoma cells. By combining RELA binding, RNA polymerase
      II (Pol II) recruitment, and perturbation of NF-kappaB activation, we demonstrate
      that kinetic differences amongst early- and late-activated RELA target genes can
      be understood based on chromatin configuration prior to cell activation and RELA
      dependent priming, respectively. We also identified genes that were repressed by
      RELA activation and others that responded to RELA-activated transcription
      factors. Cumulatively, our studies define an NF-kappaB-responsive inducible gene
      cascade in activated B cells.

PMID- 30199533
TI  - Revealing the impact of the Caucasus region on the genetic legacy of Romani
      people from genome-wide data.
AB  - Romani people are a significant minority in Europe counting about 10 million
      individuals scattered throughout the continent. They are a migratory group
      originating from Northwestern India. Their exodus from India occurred
      approximately 1000-1500 years ago. The migration route of the Romani people was
      reconstructed with the help of cultural anthropology, linguistics and historical
      records. Their migration made them through Central Asia, Middle East and the
      Caucasus region, prior to the arriving into Europe. Yet the significance of these
      regions, especially of the Caucasus, in Roma ancestry was a rather neglected
      topic. Contribution of the Caucasus and further affected regions to the ancestry
      of Roma was investigated based on genome-wide autosomal marker data. 158 European
      Roma samples and 41 populations from the Caucasus region, from Middle East,
      Central Asia and from South Asia were considered in our tests. Population
      structure and ancestry analysis algorithms were applied to investigate the
      relationship of Roma with these populations. Identical by descent DNA segment
      analyses and admixture linkage disequilibrium based tests were also applied. Our
      results suggest that the Caucasus region plays also a significant role in the
      genetic legacy of Romani people besides the main sources, Europe and South Asia,
      previously investigated by other population genetic studies. The Middle East and
      Central Asia seems slightly less important but far from negligible in connection
      with the sources of Roma ancestry. Our results point out that the Caucasus region
      and altogether the area of the Caspian and Black Seas had a significant role in
      the migration of Romani people towards Europe and contributed significantly to
      the genetic legacy of Roma rival to the European and Indian main sources.

PMID- 30199534
TI  - Economic burden of the therapeutic management of mental illnesses and its effect
      on household purchasing power.
AB  - Cost or burden of illness studies for mental illnesses has helped define the
      magnitude of their negative effects on the household, community and national
      economy. Despite its many benefits, there is a paucity of these studies among
      Nigerians being managed for mental illnesses. This study was aimed at assessing
      the economic burden of mental illnesses and its effect on household purchasing
      power. The study was descriptive cross-sectional in design conducted among 284
      out-patients with five categories of mental illnesses at the Neuropsychiatric
      Hospital, Aro recruited via a systematic sampling technique. Data collection was
      quantitative using a semi-structured interviewer-administered tool. Participants
      provided the actual direct costs and estimates of indirect costs incurred during
      their most recent inpatient admission and their first clinic visit after
      discharge. Parametric and non-parametric statistical tests were conducted on the
      direct and estimated indirect costs respectively after testing them for normality
      using the Q-Q plot with statistical significance determined at p<0.05. Almost 96%
      of respondents finance their healthcare costs by themselves or their family with
      >50% earning <US$1.8 per day. Their mean direct and estimated indirect costs were
      (US$23.1+/-US$11.3 and US$15+/-US$28). There were no statistically significant
      differences in the mean direct and estimated indirect costs incurred by
      participants across the categories of mental illnesses. A significantly higher
      proportion of participants could afford the essential goods (88%) compared to
      those who could afford luxurious goods (29%) with p<0.001. The mean direct costs
      incurred by those who could afford the essential and luxurious goods were
      significantly higher than those who could not following a t-test. The median
      estimated indirect costs incurred by those who could not afford luxurious goods
      differed significantly from those who could with the Mann Whitney U-test.
      Participants with mental illnesses face a high economic burden in managing their
      condition with the majority unable to afford luxurious goods. Affordability was
      also associated with incurring more direct costs.

PMID- 30199536
TI  - Multi-view registration of unordered range scans by fast correspondence
      propagation of multi-scale descriptors.
AB  - This paper proposes a global approach for the multi-view registration of
      unordered range scans. Our method starts with the pair-wise registration, where
      multi-scale descriptor is selected for feature point and the propagation of
      feature correspondence is accordingly accelerated. Subsequently, we design an
      effective rule to judge the reliability of these pair-wise registration results.
      According to the judgment of reliability, we propose a model fusion method, which
      can utilize reliable results of pair-wise registration to augment the model
      shape. Finally, multi-view registration can be achieved by operating the pair
      wise registration, reliability judgment, and model fusion alternately. The
      proposed approach can be applied to scene reconstruction and robot mapping.
      Experimental results conducted on public datasets show that the proposed approach
      can automatically achieve multi-view registration of unordered range scans.
      Compared with other related approaches, the proposed approach has superior
      performances in accuracy and effectiveness.

PMID- 30199535
TI  - Lupus acceleration by a MAVS-activating RNA virus requires endosomal TLR
      signaling and host genetic predisposition.
AB  - Viruses have long been implicated in the pathogenesis of autoimmunity, yet their
      contribution remains circumstantial partly due to the lack of well-documented
      information on infections prior to autoimmune disease onset. Here, we used the
      lymphocytic choriomeningitis virus (LCMV) as a model to mechanistically dissect
      the impact of viral infection on lupus-like autoimmunity. Virus persistence
      strongly enhanced disease in mice with otherwise weak genetic predisposition but
      not in highly predisposed or non-autoimmune mice, indicating a synergistic
      interplay between genetic susceptibility and virus infection. Moreover, endosomal
      Toll-like receptors (TLRs) and plasmacytoid dendritic cells (pDCs) were both
      strictly required for disease acceleration, even though LCMV also induces strong
      TLR-independent type I interferon (IFN-I) production via RNA helicases and MAVS
      in conventional DCs. These results suggest that LCMV enhances systemic
      autoimmunity primarily by providing stimulatory nucleic acids for endosomal TLR
      engagement, whereas overstimulation of the MAVS-dependent cytosolic pathway in
      the absence of endosomal TLR signaling is insufficient for disease induction.

PMID- 30199538
TI  - Providing longer post-fledging periods increases offspring survival at the
      expense of future fecundity.
AB  - The cost of reproduction is a key concept in life-history trade-offs. However,
      our understanding of the reproductive costs is biased towards measures of
      reproductive effort obtained before offspring independence. During the post
      fledging dependence period (PFDP), it is well known that parents feed and protect
      their offspring. However, the effort devoted to this reproductive activity has
      never been considered in the context of of the costs of reproduction. Moreover,
      the potential fitness benefits and costs for offspring and parents, respectively,
      of the duration of the PFDP are largely unknown. We estimated the duration of the
      PFDP over 5 years using wild common kestrels (Falco tinnunculus) and studied its
      association with survival probability and future parental reproductive
      performance. Our results show that longer PFDPs increase the survival probability
      of fledglings, probably due to the benefits obtained from parental care. In
      addition, we found that providing longer PFDPs was associated with reduced clutch
      sizes but not the number of fledglings in the subsequent breeding season in
      males. We suggest that increased parental expenditures on offspring during the
      PFDP may represent a potential cost of reproduction in breeding males.

PMID- 30199537
TI  - Random migration of induced pluripotent stem cell-derived human gastrulation
      stage mesendoderm.
AB  - Gastrulation is the initial systematic deformation of the embryo to form germ
      layers, which is characterized by the placement of appropriate cells in their
      destined locations. Thus, gastrulation, which occurs at the beginning of the
      second month of pregnancy, is a critical stage in human body formation. Although
      histological analyses indicate that human gastrulation is similar to that of
      other amniotes (birds and mammals), much of human gastrulation dynamics remain
      unresolved due to ethical and technical limitations. We used human induced
      pluripotent stem cells (hiPSCs) to study the migration of mesendodermal cells
      through the primitive streak to form discoidal germ layers during gastrulation.
      Immunostaining results showed that hiPSCs differentiated into mesendodermal cells
      and that epithelial-mesenchymal transition occurred through the activation of the
      Activin/Nodal and Wnt/beta-catenin pathways. Single-cell time-lapse imaging of
      cells adhered to cover glass showed that mesendodermal differentiation resulted
      in the dissociation of cells and an increase in their migration speed, thus
      confirming the occurrence of epithelial-mesenchymal transition. These results
      suggest that mesendodermal cells derived from hiPSCs may be used as a model
      system for studying migration during human gastrulation in vitro. Using random
      walk analysis, we found that random migration occurred for both undifferentiated
      hiPSCs and differentiated mesendodermal cells. Two-dimensional random walk
      simulation showed that homogeneous dissociation of particles may form a discoidal
      layer, suggesting that random migration might be suitable to effectively disperse
      cells homogeneously from the primitive streak to form discoidal germ layers
      during human gastrulation.

PMID- 30199539
TI  - Reduced monocyte and macrophage TNFSF15/TL1A expression is associated with
      susceptibility to inflammatory bowel disease.
AB  - Chronic inflammation in inflammatory bowel disease (IBD) results from a breakdown
      of intestinal immune homeostasis and compromise of the intestinal barrier. Genome
      wide association studies have identified over 200 genetic loci associated with
      risk for IBD, but the functional mechanisms of most of these genetic variants
      remain unknown. Polymorphisms at the TNFSF15 locus, which encodes the TNF
      superfamily cytokine commonly known as TL1A, are associated with susceptibility
      to IBD in multiple ethnic groups. In a wide variety of murine models of
      inflammation including models of IBD, TNFSF15 promotes immunopathology by
      signaling through its receptor DR3. Such evidence has led to the hypothesis that
      expression of this lymphocyte costimulatory cytokine increases risk for IBD. In
      contrast, here we show that the IBD-risk haplotype at TNFSF15 is associated with
      decreased expression of the gene by peripheral blood monocytes in both healthy
      volunteers and IBD patients. This association persists under various stimulation
      conditions at both the RNA and protein levels and is maintained after macrophage
      differentiation. Utilizing a "recall-by-genotype" bioresource for allele-specific
      expression measurements in a functional fine-mapping assay, we localize the
      polymorphism controlling TNFSF15 expression to the regulatory region upstream of
      the gene. Through a T cell costimulation assay, we demonstrate that genetically
      regulated TNFSF15 has functional relevance. These findings indicate that
      genetically enhanced expression of TNFSF15 in specific cell types may confer
      protection against the development of IBD.

PMID- 30199540
TI  - Effects of four weeks intermittent hypoxia intervention on glucose homeostasis,
      insulin sensitivity, GLUT4 translocation, insulin receptor phosphorylation, and
      Akt activity in skeletal muscle of obese mice with type 2 diabetes.
AB  - AIMS: The aims of this study were to determine the effects of four weeks of
      intermittent exposure to a moderate hypoxia environment (15% oxygen), and compare
      with the effects of exercise in normoxia or hypoxia, on glucose homeostasis,
      insulin sensitivity, GLUT4 translocation, insulin receptor phosphorylation, Akt
      dependent GSK3 phosphorylation and Akt activity in skeletal muscle of obese mice
      with type 2 diabetes. METHODS: C57BL/6J mice that developed type 2 diabetes with
      a high-fat-diet (55% fat) (fasting blood glucose, FBG = 13.9 +/- 0.69 (SD)
      mmol/L) were randomly allocated into diabetic control (DC), rest in hypoxia (DH),
      exercise in normoxia (DE), and exercise in hypoxia (DHE) groups (n = 7, each),
      together with a normal-diet (4% fat) control group (NC, FBG = 9.1 +/- 1.11 (SD)
      mmol/L). The exercise groups ran on a treadmill at intensities of 75-90% VO2max.
      The interventions were applied one hour per day, six days per week for four
      weeks. Venous blood samples were analysed for FBG, insulin (FBI) and insulin
      sensitivity (QUICKI) pre and post the intervention period. The quadriceps muscle
      samples were collected 72 hours post the last intervention session for analysis
      of GLUT4 translocation, insulin receptor phosphorylation, Akt expression and
      phosphorylated GSK3 fusion protein by western blot. Akt activity was determined
      by the ratio of the phosphorylated GSK3 fusion protein to the total Akt protein.
      RESULTS: The FBG of the DH, DE and DHE groups returned to normal level (FBG = 9.4
      +/- 1.50, 8.86 +/- 0.94 and 9.0 +/- 1.13 (SD) mmol/L for DH, DE and DHE
      respectively, P < 0.05), with improved insulin sensitivity compared to DC (P <
      0.05), after the four weeks treatment, while the NC and DC showed no significant
      changes, as analysed by general linear model with repeated measures. All three
      interventions resulted in a significant increase of GLUT4 translocation to cell
      membrane compared to the DC group (P < 0.05). The DE and DH showed a similar
      level of insulin receptor phosphorylation compared with NC that was significantly
      lower than the DC (P < 0.05) post intervention. The DH and DHE groups showed a
      significantly higher Akt activity compared to the DE, DC and NC (P < 0.05) post
      intervention, as analysed by one-way ANOVA. CONCLUSIONS: This study produced new
      evidence that intermittent exposure to mild hypoxia (0.15 FiO2) for four weeks
      resulted in normalisation of FBG, improvement in whole body insulin sensitivity,
      and a significant increase of GLUT4 translocation in the skeletal muscle, that
      were similar to the effects of exercise intervention during the same time period,
      in mice with diet-induced type 2 diabetes. However, exercise in hypoxia for four
      weeks did not have additive effects on these responses. The outcomes of the
      research may contribute to the development of effective, alternative and
      complementary interventions for management of hyperglycaemia and type 2 diabetes,
      particularly for individuals with limitations in participation of physical
      activity.

PMID- 30199541
TI  - Global DNA cytosine methylation variation in Spartina alterniflora at North
      Inlet, SC.
AB  - Spartina alterniflora, marsh grass, is a vegetative apomicticly-reproducing
      halophyte native to marshes along the east coast of the United States and
      invasive across the world. S. alterniflora provides many ecosystem services
      including, but not limited to, water filtration, habitats for invertebrates, and
      sediment retention. Widespread diebacks of longstanding marsh grass colonies
      launched extensive investigations into probable mechanisms leading to patchy
      diebacks. There is still current debate as to the causes of a marsh dieback but
      environmental stress is acknowledged as a constant. Spatial epigenetic variation
      could contribute to variation of stress susceptibility, but the scale and
      structure of epigenetic variation is unknown. The current study investigates
      patterns of epigenetic variation in a natural population of S. alterniflora. This
      study examines variation of global DNA methylation within and among clones of the
      marsh grass Spartina alterniflora using an ELISA-like microplate reaction and
      observed significant heterogeneity of global DNA methylation within and among
      clones of S. alterniflora across the North Inlet basin, as well as significant
      differences of global methylation between adults and sexually produced seedlings.
      The present study also characterized differences for plants in a section of the
      population that experienced an acute marsh dieback in the year 2001 and have
      subsequently recolonized, finding a significant positive correlation between
      cytosine methylation and time period of colonization. The significant
      heterogeneity of global DNA methylation both within and among clones observed
      within this natural population of S. alterniflora and potential impacts from
      hypersaline environments at North Inlet suggests the need for more in-depth
      epigenetic studies to fully understand DNA methylation within an ecological
      context. Future studies should consider the effects of varying saline conditions
      on both global DNA and gene specific methylation.

PMID- 30199542
TI  - A new model to predict major bleeding in patients with atrial fibrillation using
      warfarin or direct oral anticoagulants.
AB  - BACKGROUND: No scores presently exist to predict bleeding in atrial fibrillation
      (AF) populations using direct oral anticoagulants (DOACs). We used data from two
      independent healthcare claims databases to develop and validate a predictive
      model of major bleeding in a contemporary AF population. METHODS: Patients with
      non-valvular AF initiating oral anticoagulation were identified in the MarketScan
      databases from 2007-2014. Using Cox regression models in 1000 bootstrapped
      samples, we developed a model that selected variables predicting major bleeding
      in the first year after anticoagulant initiation. The final model was validated
      in patients with non-valvular AF in the Optum Clinformatics database in the
      period 2009-2015. The discriminative ability of existing bleeding scores were
      individually evaluated and compared with the new bleeding model termed
      Anticoagulation-specific Bleeding Score (ABS) in both MarketScan and Optum.
      RESULTS: Among 119,083 patients with AF initiating oral anticoagulation in the
      derivation cohort, 4,030 experienced a bleeding event. The variable selection
      model identified 15 variables (including individual type of oral anticoagulant)
      associated with major bleeding. Discrimination of the model was modest [c
      statistic 0.68, 95% confidence interval (CI) 0.67-0.69]. The model was
      subsequently applied to 81,285 AF patients in the validation data set (3,238
      bleeding events), showing similar discrimination (c-statistic 0.68, 95% CI 0.67
      0.69). In both cohorts, the predictive performance of the ABS was better than the
      existing models for bleeding prediction in AF. CONCLUSIONS: We developed a model
      that uses administrative healthcare data for the identification of AF patients at
      higher risk of bleeding after initiation of oral anticoagulation, taking into
      account the lower bleeding risk in DOAC compared to warfarin users.

PMID- 30199543
TI  - Multiple insecticide resistance mechanisms in primary dengue vector, Aedes
      aegypti (Linn.) from dengue endemic districts of sub-Himalayan West Bengal,
      India.
AB  - BACKGROUND: Mosquitoes belonging to genus Aedes are the prime vectors of several
      arboviral diseases such as Dengue, Zika and Chikungunya worldwide. Every year
      numerous cases of dengue infections occur throughout the world, proper control of
      which depends on efficient vector control. However the onset of insecticide
      resistance has resulted in failure of vector control approaches. PRINCIPAL
      FINDINGS: This study was carried out to unveil the degree of prevailing
      insecticide resistance along with its underlying mechanisms among the primary
      dengue vector in dengue endemic districts of West Bengal, India through standard
      WHO protocol. It was observed that, the majority of the tested populations were
      found to possess resistance to more than one insecticide. In adult bioassay, the
      toxicity levels of the six tested insecticides was found to decrease in the
      following order: deltamethrin > lambdacyhalothrin > malathion > propoxur >
      permethrin > DDT. In larval bioassay, one of the tested populations was found to
      possess moderate resistance against temephos, mortality percentage 92.5% and
      79.8% for WHO (0.0200 ppm) and National Vector Borne disease Programme, India
      recommended dose (0.0125 ppm) respectively. Carboxylesterases were found to be
      involved in conferring resistance as revealed in synergistic and quantitative
      assay against temephos in North Dinajpur (NDP) population and malathion in
      Alipurduar (APD) and Darjeeling (DAR) populations. Similar correlations were also
      observed in the majority of the tested populations between reduced
      susceptibilities against pyrethroid insecticides and Cytochrome P450s activity.
      CONCLUSION: Efficient disease management in this region can only be achieved
      through proper integrated vector management along with tools to minimize
      insecticide resistance. This study may help the concerned authorities in the
      formulation of an effective vector control strategy throughout this region
      incorporating the knowledge gained through this study.

PMID- 30199546
TI  - Why is the inpatient cost of dying increasing in India?
AB  - INTRODUCTION: There is an evidence of increasing inpatient expenditure for
      decedents. Estimates used to assess the economic burden of out-of-pocket (OOP)
      healthcare expenditure provide an underestimation for inpatient decedent cases.
      The aims of this paper are to study the trend and pattern of inpatient decedent
      expenditure and decipher the reasons behind the increasing cost in India.
      METHODS: Using three rounds of national level National Sample Survey (NSS) data
      on morbidity & healthcare conducted during 1995-2015 in India, total and
      component-wise cost of dying was estimated by the socio-demographic
      characteristics and types of diseases. Generalised linear model was employed to
      find the changing effect of inpatient decedents on inpatient expenditure on three
      time points. RESULTS: More than half among inpatient decedents were elderly. Mean
      inpatient expenditure for neoplasm, circulatory system-related diseases and
      external causes of mortality and morbidity increased substantially during these
      two decades. Mean decedent inpatient expenditure become double, diagnostic and
      bed charges increased by 243%, 323% respectively during 2004-05 to 2014-15.
      During 2014-15 average decedents aged 15-59 years spent ?53599 in last twelve
      month of their life. Controlling all other potential factors, the inpatient
      expenditure among decedents increased substantially between 1995-96 and 2014-15.
      DISCUSSION: Out-of-pocket inpatient health expenditure widened between survivor
      and decedents in between 1995-2014. Increase in the proportion of elderly,
      proportion of non-communicable and lifestyle-related diseases, expenses on drugs,
      diagnostics, bed charges largely private sector expenses were the leading reasons
      for increasing inpatient decedent expenditure. Age-based risk adjustment and
      modification of end-of-life care are strongly required, future social insurance
      based on the health-based value of out-of-pocket expenditure rather than their
      pure consumption value need to be designed to tackle the burden.

PMID- 30199544
TI  - Pharmacologic rescue of hyperammonemia-induced toxicity in zebrafish by
      inhibition of ornithine aminotransferase.
AB  - Hyperammonemia is the common biochemical hallmark of urea cycle disorders,
      activating neurotoxic pathways. If untreated, affected individuals have a high
      risk of irreversible brain damage and mortality. Here we show that acute
      hyperammonemia strongly enhances transamination-dependent formation of osmolytic
      glutamine and excitatory glutamate, thereby inducing neurotoxicity and death in
      ammoniotelic zebrafish larvae via synergistically acting overactivation of NMDA
      receptors and bioenergetic impairment induced by depletion of 2-oxoglutarate.
      Intriguingly, specific and irreversible inhibition of ornithine aminotransferase
      (OAT) by 5-fluoromethylornithine rescues zebrafish from lethal concentrations of
      ammonium acetate and corrects hyperammonemia-induced biochemical alterations.
      Thus, OAT inhibition is a promising and effective therapeutic approach for
      preventing neurotoxicity and mortality in acute hyperammonemia.

PMID- 30199548
TI  - Correction: Wnt11 Is Required for Oriented Migration of Dermogenic Progenitor
      Cells from the Dorsomedial Lip of the Avian Dermomyotome.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0092679.].

PMID- 30199547
TI  - An event-related potential study of spatial working memory in binge drinking
      college students.
AB  - This study used event-related potentials (ERPs) and a modified spatial 2-back
      task to investigate spatial working memory in binge drinking (BD) college
      students. Based on the Korean version of the Alcohol Use Disorder Identification
      Test (AUDIT-K) and Alcohol Use Questionnaire (AUQ) scores, participants were
      assigned into BD (n = 25) and non-BD (n = 25) groups. The modified spatial 2-back
      task includes congruent, incongruent, and lure conditions and participants are
      required to respond as rapidly and accurately as possible to the congruent
      stimuli but not to the incongruent and lure stimuli. The BD and non-BD groups
      exhibited comparable performances on the spatial 2-back task but the BD group
      showed significantly larger P3 amplitudes than the non-BD group. Additionally,
      the non-BD group showed larger P3 amplitudes in response to the congruent stimuli
      compared to the incongruent and lure stimuli whereas the P3 amplitudes in the BD
      group did not differ significantly among the three conditions. These results
      indicate that the BD individuals exerted greater effort to maintain performance
      levels comparable to non-BD individuals and that they were less efficient in
      differentiating or allocating attentional resources between relevant and
      irrelevant information.

PMID- 30199545
TI  - Physiological and pathological roles of FATP-mediated lipid droplets in
      Drosophila and mice retina.
AB  - Increasing evidence suggests that dysregulation of lipid metabolism is associated
      with neurodegeneration in retinal diseases such as age-related macular
      degeneration and in brain disorders such as Alzheimer's and Parkinson's diseases.
      Lipid storage organelles (lipid droplets, LDs), accumulate in many cell types in
      response to stress, and it is now clear that LDs function not only as lipid
      stores but also as dynamic regulators of the stress response. However, whether
      these LDs are always protective or can also be deleterious to the cell is
      unknown. Here, we investigated the consequences of LD accumulation on retinal
      cell homeostasis under physiological and stress conditions in Drosophila and in
      mice. In wild-type Drosophila, we show that dFatp is required and sufficient for
      expansion of LD size in retinal pigment cells (RPCs) and that LDs in RPCs are
      required for photoreceptor survival during aging. Similarly, in mice, LD
      accumulation induced by RPC-specific expression of human FATP1 was non-toxic and
      promoted mitochondrial energy metabolism in RPCs and non-autonomously in
      photoreceptor cells. In contrast, the inhibition of LD accumulation by dFatp
      knockdown suppressed neurodegeneration in Aats-metFB Drosophila mutants, which
      carry elevated levels of reactive oxygen species (ROS). This suggests that
      abnormal turnover of LD may be toxic for photoreceptors cells of the retina under
      oxidative stress. Collectively, these findings indicate that FATP-mediated LD
      formation in RPCs promotes RPC and neuronal homeostasis under physiological
      conditions but could be deleterious for the photoreceptors under pathological
      conditions.

PMID- 30199550
TI  - Increased maternal hCG concentrations in early in vitro pregnancy with elevated
      basal FSH.
AB  - OBJECTIVE: To investigate factors that influence maternal hCG concentration in
      early pregnancy and the relationship between hCG concentration in early pregnancy
      and basal FSH (bFSH) level. DESIGN: Retrospective cohort study. SETTING:
      Reproductive medical center. PATIENT(S): In total, 482 women aged 22 to 38 years
      with elevated basal FSH (> 10 IU/L) and who experienced a single live birth after
      in vitro fertilization-embryo transfer were selected. These 482 women were age
      matched with an equal number of women with normal basal FSH (<=10 IU/L) who also
      experienced a single live birth. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S):
      HCG concentration. RESULT(S): The hCG concentrations on Day 14 and Day 21 were
      560.46 (363.63-842.52) IU/L and 9862.00 (6512.25-14029.50) IU/L, respectively, in
      the elevated bFSH group, and these values were significantly increased compared
      with the normal bFSH group. After adjusting for confounding factors, the
      concentrations of maternal hCG on Day 14 and Day 21 were significantly associated
      with basal FSH. In addition, crude linear regression analysis demonstrated that
      hCG concentrations increased as the basal serum levels of FSH increased.
      CONCLUSION(S): Elevated basal FSH has implications for the interpretation of hCG
      concentrations in early pregnancy after in vitro fertilization-embryo transfer
      (IVF-ET) that led to a single live birth.

PMID- 30199549
TI  - The significance of human respiratory syncytial virus (HRSV) in children from
      Ghana with acute lower respiratory tract infection: A molecular epidemiological
      analysis, 2006 and 2013-2014.
AB  - BACKGROUND: Acute lower respiratory tract infection (ALRI) is a leading cause of
      childhood morbidity and mortality in developing countries. Globally, human
      respiratory syncytial virus (HRSV) is the most common pathogen of ALRI in infants
      and children. However, age-stratified HRSV disease burden data are largely absent
      from Africa, which is a key gap in informing an evidence-based recommendation for
      the introduction of an HRSV vaccine by the WHO. METHODS: This study investigated
      the presence of HRSV in respiratory specimens from 552 children <5 years old with
      ALRI from Accra, Ghana in 2006 and 2013-2014 by real-time PCR. Of HRSV-positive
      samples the second hypervariable region of the viral G protein gene was sequenced
      and analyzed for phylogeny, characteristic amino acid substitutions, and
      potential glycosylation patterns. Further, HRSV infections have been
      characterized by age, symptoms and timely occurrence. RESULTS: HRSV was observed
      in 23% (127/552) of the children with ALRI, with the highest incidence in infants
      younger than one year (33%, 97/295, p = 0.013). Within the observed seasonal
      circulation time of HRSV from June (mid-wet season) to December (beginning of the
      dry season) the incidence of ALRI due to HRSV was as high as 46% (125/273). HRSV
      disease was significantly associated with (broncho-) pneumonia, bronchiolitis,
      LRTI, and difficulty in breathing. Phylogenetic characterization of HRSV strains
      from Ghana identified the circulation of the currently worldwide prevailing
      genotypes ON1 and BA9, and shows evidence of an independent molecular evolution
      of ON1 and BA9 strains in Ghana resulting in potentially new subgenotypes within
      ON1 and BA9, provisionally named ON1.5, ON1.6, and BA9-IV. CONCLUSION: This study
      addresses important knowledge gaps in the forefront of introducing the HRSV
      vaccine by providing information on the molecular evolution and incidence of HRSV
      in Accra (Ghana, Africa).

PMID- 30199552
TI  - Electrical field-induced contractions on Crotalus durissus terrificus and
      Bothrops jararaca aortae are caused by endothelium-derived catecholamine.
AB  - Endothelium is the main source of catecholamine release in the electrical-field
      stimulation (EFS)-induced aortic contractions of the non- venomous snake
      Panterophis guttatus. However, adrenergic vasomotor control in venomous snakes
      such as Crotalus durissus terrificus and Bothrops jararaca has not yet been
      investigated. Crotalus and Bothrops aortic rings were mounted in an organ bath
      system. EFS-induced aortae contractions were performed in the presence and
      absence of guanethidine (30 MUM), phentolamine (10 MUM) or tetrodotoxin (1 MUM).
      Frequency-induced contractions were also performed in aortae with endothelium
      removed. Immunohistochemical localization of both tyrosine hydroxylase (TH) and S
      100 protein in snake aortic rings and brains, as well as in human tissue
      (paraganglioma tumour) were carried out. EFS (4 to 16 Hz) induced frequency
      dependent aortic contractions in both Crotalus and Bothrops. The EFS-induced
      contractions were significantly reduced in the presence of either guanethidine or
      phentolamine in both snakes (p<0.05), whereas tetrodotoxin had no effect in
      either. Removal of the endothelium abolished the EFS-induced contractions in both
      snakes aortae (p<0.05). Immunohistochemistry revealed TH localization in
      endothelium of both snake aortae and human vessels. Nerve fibers were not
      observed in either snake aortae. In contrast, both TH and S100 protein were
      observed in snake brains and human tissue. Vascular endothelium is the main
      source of catecholamine release in EFS-induced contractions in Crotalus and
      Bothrops aortae. Human endothelial cells also expressed TH, indicating that
      endothelium- derived catecholamines possibly occur in mammalian vessels.

PMID- 30199551
TI  - Euthanasia of laboratory mice: Are isoflurane and sevoflurane real alternatives
      to carbon dioxide?
AB  - In the European Union (EU) millions of laboratory mice are used and killed for
      experimental and other scientific purposes each year. Although controversially
      discussed, the use of carbon dioxide (CO2) is still permitted for killing rodents
      according to the Directive 2010/63/EU. Within the scope of refinement, our aim
      was to investigate if isoflurane and sevoflurane are an appropriate alternative
      killing method to CO2 in mice. Different concentrations of CO2 (filling rates of
      20%, 60%, 100%; CO2 20, 60, 100), isoflurane (Iso 2%, 5%) and sevoflurane (Sevo
      4.8%, 8%) were compared in two mouse strains (NMRI, C57Bl/6J) using a broad
      spectrum of behavioral parameters, including the approach-avoidance test, and
      analyzing blood for stress parameters (glucose, adrenaline, noradrenaline). We
      focused in our study on the period from the beginning of the gas inlet to loss of
      consciousness, as during this period animals are able to perceive pain and
      distress. Our results show that only higher concentrations of CO2 (CO2 60, 100)
      and isoflurane (5%) induced surgical tolerance within 300 s in both strains, with
      CO2 100 being the fastest acting inhalant anesthetic. The potency of halogenated
      ethers depended on the mouse strain, with C57Bl/6J being more susceptible than
      NMRI mice. Behavioral analysis revealed no specific signs of distress, e. g.
      stress-induced grooming, and pain, i. e. audible vocalizations, for all inhalant
      gases. However, adrenaline and noradrenaline plasma concentrations were
      increased, especially in NMRI mice exposed to CO2 in high concentrations, whereas
      we did not observe such increase in animals exposed to isoflurane or sevoflurane.
      Escape latencies in the approach-avoidance test using C57Bl/6J mice did not
      differ between the three inhalant gases, however, some animals became recumbent
      during isoflurane and sevoflurane but not during CO2 exposure. The rise in
      catecholamine concentrations suggests that CO2 exposure might be linked to a
      higher stress response compared to isoflurane and sevoflurane exposure, although
      we did not observe a behavioral correlate for that. Follow-up studies
      investigating other fast-acting stress hormones and central anxiety circuits are
      needed to confirm our findings.

PMID- 30199553
TI  - Association of Epithelial Mesenchymal Transition with prostate and breast health
      disparities.
AB  - African Americans (AA) have higher death rates due to prostate and breast cancer
      as compared to Caucasian Americans (CA), and few biomarkers have been associated
      with this disparity. In our study we investigated whether epithelial-mesenchymal
      transition (EMT) with a focus on Snail and Cathepsin L (Cat L), could potentially
      be two markers associated with prostate and breast health disparities. We have
      previously shown that Snail can increase Cat L protein and activity in prostate
      and breast cancer. Western blot and real-time PCR analyses showed that
      mesenchymal protein expression (Snail, vimentin, Cat L) and Cat L activity (shown
      by zymography) was higher in AA prostate cancer cells as compared to CA normal
      transformed RWPE-1 prostate epithelial cells, and androgen-dependent cells, and
      comparable to metastatic CA cell lines. With respect to breast cancer,
      mesenchymal markers were higher in TNBC compared to non-TNBC cells. The higher
      mesenchymal marker expression was functionally associated with higher
      proliferative and migratory rates. Immunohistochemistry showed that both nuclear
      Snail and Cat L expression was significantly higher in cancer compared to normal
      for CA and Bahamas prostate patient tissue. Interestingly, AA normal tissue
      stained higher for nuclear Snail and Cat L that was not significantly different
      to cancer tissue for both prostate and breast tissue, but was significantly
      higher than CA normal tissue. AA TNBC tissue also displayed significantly higher
      nuclear Snail expression compared to CA TNBC, while no significant differences
      were observed with Luminal A cancer tissue. Therefore, increased EMT in AA
      compared to CA that may contribute to the more aggressive disease.

PMID- 30199556
TI  - How do housing prices affect consumption in China? New evidence from a continuous
      wavelet analysis.
AB  - In this paper, we revisit the relationship between housing prices and consumption
      in China by using a continuous wavelet analysis. This method provides an insight
      into the dynamic nexus in both time and frequency domains. In general, Empirical
      results show that there is a positive relationship between the two series in
      China, although it varies across time and frequencies. First, we find that
      disposable income is the core factor which affects both consumption and housing
      prices in China. Second, housing prices have a weak wealth effect on consumption
      in most time. High housing ownership and proportion of housing asset in the total
      household asset lead to a wealth effect of housing prices on consumption. Third,
      in the long term, there is a significant wealth effect of housing prices on
      consumption, but it weakens after 2008, which implies that excessively high
      housing prices in recent years have partially constrained residents' consumption.
      These findings have important implications for seeking housing market regulation
      and expanding domestic consumption decisions.

PMID- 30199555
TI  - Risk of adverse outcomes following urinary tract infection in older people with
      renal impairment: Retrospective cohort study using linked health record data.
AB  - BACKGROUND: Few studies have investigated the risk of adverse outcomes in older
      people with renal impairment presenting to primary care with a urinary tract
      infection (UTI). The aim of this study was to determine the risk of adverse
      outcomes in patients aged >=65 years presenting to primary care with a UTI, by
      estimated glomerular filtration rate (eGFR) and empirical prescription of
      nitrofurantoin versus trimethoprim. METHODS AND FINDINGS: This was a
      retrospective cohort study using linked health record data from 795,484 patients
      from 393 general practices in England, who were aged >=65 years between 2010 and
      2016. Patients were entered into the cohort if they presented with a UTI and had
      a creatinine measurement in the 24 months prior to presentation. We calculated an
      eGFR to estimate risk of adverse outcomes by renal function, and propensity-score
      matched patients with eGFRs <60 mL/minute/1.73 m2 to estimate risk of adverse
      outcomes between those prescribed trimethoprim and nitrofurantoin. Outcomes were
      14-day risk of reconsultation for urinary symptoms and same-day antibiotic
      prescription (proxy for treatment nonresponse), hospitalisation for UTI, sepsis,
      or acute kidney injury (AKI), and 28-day risk of death. Of 123,607 eligible
      patients with a UTI, we calculated an eGFR for 116,945 (95%). Median age was 76
      (IQR, 70-83) years and 32,428 (28%) were male. Compared to an eGFR of >60
      mL/minute/1.73 m2, patients with an eGFR of <60 mL/minute/1.73 m2 had greater
      odds of hospitalisation for UTI (adjusted odds ratios [ORs] ranged from 1.14 [95%
      confidence interval (CI) 1.01-1.28, p = 0.028], for eGFRs of 45-59, to 1.68 [95%
      CI 1.01-2.82, p < 0.001] for eGFRs <15) and AKI (adjusted ORs ranged from 1.57
      [95% CI 1.29-1.91, p < 0.001], for eGFRs of 45-59, to 4.53 [95% CI 2.52-8.17, p <
      0.001] for eGFRs <15). Compared to an eGFR of >60 mL/minute/1.73 m2, patients
      with an eGFR <45 had significantly greater odds of hospitalisation for sepsis,
      and those with an eGFR <30 had significantly greater odds of death. Compared to
      trimethoprim, nitrofurantoin prescribing was associated with lower odds of
      hospitalisation for AKI (ORs ranged from 0.62 [95% CI 0.40-0.94, p = 0.025], for
      eGFRs of 45-59, to 0.45 [95% CI 0.25-0.81, p = 0.008] for eGFRs <30).
      Nitrofurantoin was not associated with greater odds of any adverse outcome. Our
      study lacked data on urine microbiology and antibiotic-related adverse events.
      Despite our design, residual confounding may still have affected some of our
      findings. CONCLUSIONS: Older patients with renal impairment presenting to primary
      care with a UTI had an increased risk of UTI-related hospitalisation and death,
      suggesting a need for interventions that reduce the risk of these adverse
      outcomes. Nitrofurantoin prescribing was not associated with an increased risk of
      adverse outcomes in patients with an eGFR <60 mL/minute/1.73 m2 and could be used
      more widely in this population.

PMID- 30199554
TI  - Plasmodium vivax Pv12 B-cell epitopes and HLA-DRbeta1*-dependent T-cell epitopes
      in vitro antigenicity.
AB  - Malaria is an infectious disease caused by parasites from the genus Plasmodium
      (P. falciparum and P. vivax are responsible for 90% of all clinical cases); it is
      widely distributed throughout the world's tropical and subtropical regions. The
      P. vivax Pv12 protein is involved in invasion, is expressed on merozoite surface
      and has been recognised by antibodies from individuals exposed to the disease. In
      this study, B- and T-cell epitopes from Pv12 were predicted and characterised to
      advance in the design of a peptide-based vaccine against malaria. For evaluating
      the humoral response of individuals exposed to natural P. vivax infection from
      two endemic areas in Colombia, BepiPred-1.0 software was used for selecting B
      cell epitopes. B-cell epitope 39038 displayed the greatest recognition by
      naturally-acquired antibodies and induced an IgG2/IgG4 response. NetMHCIIpan-3.1
      prediction software was used for selecting peptides having high affinity binding
      for HLA-DRbeta1* allele lineages and this was confirmed by in-vitro binding
      assays. T-epitopes 39113 and 39117 triggered a memory T-cell response
      (Stimulation Index>=2) and significant cytokine production. Combining in-silico,
      in-vitro and functional assays, two Pv12 protein regions (containing peptides
      39038, 39040, 39113 and 39117) have thus been characterised as promising vaccine
      candidates against P. vivax malaria.

PMID- 30199557
TI  - Reflections on End-of-Life Dialysis.

PMID- 30199558
TI  - A teenage patient with autosomal recessive polycystic kidney disease, a
      splenorenal shunt, and congenital hepatic fibrosis: a case report.
AB  - A 16-year-old female patient previously diagnosed with autosomal recessive
      polycystic kidney disease (ARPKD) presented with acute bilateral pneumonia, upper
      gastrointestinal bleeding caused by ruptured esophageal varices, ascites, and
      lower limb edema. She required intensive care and an endoscopic procedure to
      treat the gastrointestinal bleeding. The analysis of the differential diagnosis
      for chronic liver disease indicated she had a spontaneous splenorenal shunt.
      Ultrasound-guided biopsy revealed the patient had cirrhosis, as
      characteristically seen in individuals with ARPKD. She had no symptoms at
      discharge and was referred for review for a combined transplant.

PMID- 30199559
TI  - Oral manifestations of renal tubular acidosis associated with secondary rickets:
      case report.
AB  - This report describes the oral manifestations of renal tubular acidosis (RTA)
      associated with secondary rickets and discusses the biological plausibility of
      these findings. The characteristic electrolyte changes during RTA or genetic
      mutations that trigger RTA may be responsible for impaired amelogenesis, dental
      malocclusion, impacted teeth, and absent lamina dura. This report reinforces the
      possibility of an association between RTA and the oral manifestations described.

PMID- 30199560
TI  - Anca-associated crescentic glomerulonephritis in a child with isolated renal
      involvement.
AB  - Pauci-immune glomerulonephritis (GN) is more common in elderly people compared to
      children and the etiology is not completely understood yet. Antineutrophil
      cytoplasmic antibody (ANCA) positivity occurs in 80% of the patients. We report a
      case of a 7-year-old girl who presented with malaise and mildly elevated
      creatinine diagnosed as ANCA-associated pauci-immune crescentic
      glomerulonephritis with crescents in 20 of 25 glomeruli (80%). Of these 20
      crescents, 12 were cellular, 4 fibrocellular, and 4 globally sclerotic. She did
      not have purpura, arthritis, or systemic symptoms and she responded well to
      initial immunosuppressive treatment despite relatively severe histopathology. The
      patient was given three pulses of intravenous methylprednisolone (30 mg/kg on
      alternate days) initially and continued with cyclophosphamide (CYC; 2 mg/kg per
      day) orally for 3 months with prednisone (1 mg/kg per day). In one month,
      remission was achieved with normal serum creatinine and prednisone was gradually
      tapered. The case of this child with a relatively rare pediatric disease
      emphasizes the importance of early and aggressive immunosuppressive treatment in
      patients with renal-limited ANCA-associated pauci-immune crescentic GN even if
      with a mild clinical presentation. As in our patient, clinical and laboratory
      findings might not always exactly reflect the severity of renal histopathology
      and thus kidney biopsy is mandatory in such children to guide the clinical
      management and predict prognosis.

PMID- 30199561
TI  - Outcomes of Re-treatment by LASIK After SMILE.
AB  - PURPOSE: To report the outcomes of LASIK re-treatments after small incision
      lenticule extraction (SMILE). METHODS: Retrospective review of all eyes to have
      undergone a re-treatment by LASIK after primary SMILE between September 2013 and
      January 2016. Thin-flap LASIK was used in most cases as long as sufficient tissue
      was available for safe flap creation between the maximum epithelial thickness and
      minimum cap thickness. Otherwise, the SMILE interface was converted into a LASIK
      flap by the Circle technique or side cut only. The multivariate nomogram for
      LASIK re-treatments was used, including sphere, cylinder, age, and primary
      spherical equivalent (SEQ) as variables. Patients were observed for 1 year after
      surgery and standard outcomes analysis was performed. RESULTS: A total of 116
      LASIK re-treatments were performed in a population of 2,643 consecutive SMILE
      procedures, indicating a re-treatment rate of 4.39%. Mean attempted SEQ was -0.05
      +/- 0.99 diopters (D) (range: -1.88 to +1.50 D). Mean cylinder was -0.70 +/- 0.55
      D (range: 0.00 to -2.25 D). Postoperative uncorrected distance visual acuity was
      20/20 or better in 81% of eyes, for a population with corrected distance visual
      acuity (CDVA) of 20/20 or better in 95% before re-treatment. Mean postoperative
      SEQ relative to the target was +0.19 +/- 0.49 D (range: -0.88 to +2.13 D), with
      74% within +/-0.50 D. Mean postoperative cylinder was -0.29 +/- 0.24 D (range:
      0.00 to -1.25 D). There was one line loss of CDVA in 15% of eyes, but no eyes
      lost two or more lines. There was a small increase in contrast sensitivity (P <
      .05). Overcorrection was identified in myopic re-treatments (n = 20) of -1.00 D
      or more; mean postoperative SEQ was +0.59 +/- 0.64 D (range: -0.63 to +2.13 D).
      CONCLUSIONS: Re-treatment after SMILE by LASIK achieved excellent visual and
      refractive outcomes, although these results indicate that myopic LASIK
      retreatment after primary myopic SMILE requires a different nomogram than for
      myopic LASIK re-treatment after primary myopic LASIK. [J Refract Surg.
      2018;34(9):578-588.].

PMID- 30199562
TI  - Contrast Sensitivity After Wavefront-Guided and Wavefront-Optimized PRK and LASIK
      for Myopia and Myopic Astigmatism.
AB  - PURPOSE: To compare contrast sensitivity among participants undergoing wavefront
      guided or wavefront-optimized photorefractive keratectomy (PRK) or LASIK for the
      treatment of myopia or myopic astigmatism 12 months after surgery. METHODS: In a
      prospective, randomized clinical trial, 215 participants with myopia ranging from
      -0.50 to -7.25 diopters (D) and less than -3.50 D of manifest astigmatism
      electing to undergo either LASIK or PRK were randomized to receive wavefront
      guided or wavefront-optimized treatment. Corrected Super Vision Test (Precision
      Vision, La Salle, IL) high contrast and small letter contrast sensitivity,
      uncorrected postoperative contrast sensitivity function, and uncorrected and
      corrected distance visual acuity were measured preoperatively and at 1, 3, 6, and
      12 months postoperatively. RESULTS: There was a significant difference within
      each of the four groups over time when measuring high contrast visual acuity (P <
      .001) and small letter contrast sensitivity (P < .001), with the most significant
      decrease occurring 1 month postoperatively. However, there were no significant
      differences when comparing the four groups for high contrast sensitivity (P =
      .22) or small letter contrast sensitivity (P = .06). The area under the logarithm
      of contrast sensitivity function did not differ significantly over time (P = .09)
      or between groups (P = .16). A pairwise comparison of preoperative to 12-month
      CDVA showed a significant improvement in all groups (P < .017). The change in
      CDVA was also significantly different between groups as determined by one-way
      analysis of variance (P = .003). CONCLUSIONS: Wavefront-guided and wavefront
      optimized PRK and LASIK procedures maintained high contrast, small letter
      contrast sensitivity, and contrast sensitivity function 12 months
      postoperatively. Although the recovery period for visual performance was longer
      for PRK versus LASIK, there was no significant difference in treatment type or
      treatment profile at 12 months postoperatively. [J Refract Surg. 2018;34(9):590
      596.].

PMID- 30199563
TI  - Vision-Related Quality of Life and Perception of Military Readiness and
      Capabilities Following Refractive Surgery Among Active Duty U.S. Military Service
      Members.
AB  - PURPOSE: To assess vision-related quality of life and military readiness and
      capabilities among active duty U.S. military service members undergoing
      refractive surgery. METHODS: In this prospective, single-center, observational
      study, active duty U.S. military service members electing to undergo refractive
      surgery were asked to complete a military performance questionnaire and the
      National Eye Institute Refractive Error Quality of Life Instrument (NEI RQL-42)
      preoperatively and at 6 months postoperatively. On the military performance
      questionnaire, participants rated (1 = very bad to 5 = very good) how they felt
      their vision affected their military readiness and capabilities after refractive
      surgery. RESULTS: Among 360 participants at 6 months postoperatively, the overall
      mean military performance score increased from 3.6 +/- 0.8 to 4.8 +/- 0.3, a
      change of 1.2, with 91.7% of the participants indicating an overall improvement
      in readiness and capability (P < .001). Scores measuring overall individual
      readiness, contribution to unit's mission, use of night vision goggles, function
      at night, weapons sighting ability, employment of personal masks, weather extreme
      environmental conditions, and optical support were significantly higher
      postoperatively (P < .001). For the NEI RQL-42, scores were significantly higher
      postoperatively for the subscales clarity of vision, expectations, near vision,
      far vision, diurnal fluctuations, activity limit, glare, dependence on
      correction, worry, appearance, and satisfaction with correction (all P < .001),
      but not for symptoms after refractive surgery (P = .403). CONCLUSIONS: Refractive
      surgery significantly improves military readiness and capabilities and vision
      related quality of life of active duty U.S. military service members with
      refractive error. [J Refract Surg. 2018;34(9):597-603.].

PMID- 30199564
TI  - Flap-Lift LASIK 10 or More Years After Primary LASIK.
AB  - PURPOSE: To evaluate the safety and efficacy of flap-lift LASIK performed 10 or
      more years after the original LASIK procedure. METHODS: All patients who were
      treated with flap-lift LASIK 10 or more years after primary LASIK for whom
      records of the primary treatment could be obtained and at least 45-day follow-up
      refractions after re-treatment were available were included in this study. A
      total of 23 eyes of 20 patients were identified. The median time between primary
      LASIK and flap-lift LASIK was 13.9 years (range: 10 to 18.7 years). RESULTS: A
      total of 22 of 23 eyes (96%) retained the same corrected distance visual acuity
      (CDVA) postoperatively that was present preoperatively. One of 23 eyes (4%)
      experienced a loss of CDVA from 20/20 to 20/25 as the result of clinically
      significant epithelial ingrowth requiring multiple treatments followed by
      photorefractive keratectomy (PRK) treatment. One additional eye experienced
      clinically significant epithelial ingrowth that required a single surgical
      treatment. Fourteen of 20 eyes with a goal of plano achieved uncorrected distance
      visual acuity (UDVA) of 20/20 or better and 6 eyes achieved UDVA of 20/25 (2 of
      these eyes had preoperative CDVA of 20/25). For the eyes with a goal of plano, 16
      of 20 eyes (80%) achieved UDVA equal to the preoperative CDVA. CONCLUSIONS: Flap
      lift LASIK is an effective treatment for refractive error when performed between
      10 and 18.7 years after the initial flap was created. Epithelial ingrowth is the
      major complication, occurring to a clinically significant degree in 9% of the
      eyes. [J Refract Surg. 2018;34(9):604-609.].

PMID- 30199565
TI  - Rate of Unplanned Vitrectomies in Femtosecond Laser-Assisted Cataract Surgery
      Compared to Conventional Phacoemulsification.
AB  - PURPOSE: To assess the rate of unplanned vitrectomies with femtosecond laser
      assisted cataract surgery (FLACS) compared to conventional phacoemulsification at
      a single, high-volume, multi-surgeon ambulatory surgical center. METHODS:
      Retrospective, comparative study of phacoemulsification cases performed in a
      community-based ambulatory surgical center. A chart review of 2,480 consecutive
      FLACS procedures performed by 30 surgeons and 36,865 consecutive conventional
      phacoemulsification surgeries performed by 47 surgeons was conducted. The rate of
      unplanned vitrectomies was evaluated. In eyes with unplanned vitrectomy, the
      rates of posterior capsule tear, anterior capsule tear, and zonular dehiscence
      were analyzed. The unplanned vitrectomy rates between early and late FLACS cases
      were compared using thresholds of greater than 10, 20, and 50 cases. RESULTS:
      There were 230 (0.62%) and 16 (0.65%) unplanned vitrectomies in the conventional
      phacoemulsification and FLACS groups, respectively (P = .89). Of the cases
      requiring unplanned vitrectomy, posterior capsule tear, anterior capsule tear,
      and zonular dehiscence rates (conventional phacoemulsification vs FLACS) were
      70.9% versus 56.3%, 8.3% versus 12.5%, and 20.9% versus 31.3%, respectively (P =
      .35). The difference in unplanned vitrectomy rates between early and late cases
      did not reach statistical significance in any threshold group. CONCLUSIONS: FLACS
      had a rate of unplanned vitrectomy comparable to conventional
      phacoemulsification. There was no statistically significant difference in
      unplanned vitrectomy rates between early and late FLACS cases suggesting a short
      learning curve. [J Refract Surg. 2018;34(9):610-614.].

PMID- 30199566
TI  - Comparison of Corneal Tomography and a New Combined Tomographic Biomechanical
      Index in Subclinical Keratoconus.
AB  - PURPOSE: To investigate and compare the diagnostic ability of corneal tomography
      and biomechanical and combined parameters for detection of corneal ectasia.
      METHODS: Consecutive patients with subclinical keratoconus (SCKC) and age-matched
      controls were included. Only one eye from each patient was selected for analysis.
      The final D value from the Belin/Ambrosio Enhanced Ectasia Display (BAD) was
      obtained from the Pentacam (Oculus Optikgerate, Wetzlar, Germany). The
      tomographic biomechanical index (TBI) was derived from the Pentacam and Corvis ST
      (Oculus Optikgerate). Classification analysis between normal and subclinical
      keratoconus (SCKC) was evaluated using receiver operating characteristic (ROC)
      curves. The area under the ROC curve (AUC) and partial AUC (pAUC) with
      specificity of 80% or greater were compared. RESULTS: Twenty-three eyes with SCKC
      and 37 normal eyes were included. All Pentacam-derived parameters (P < .001) and
      all but two Corvis ST-derived parameters (P < .020) were significantly different
      between normal and SCKC eyes. A significant difference was found in the final D
      value (P <= .020) and TBI (P <= .040) between normal and SCKC eyes. For
      differentiating normal and SCKC eyes, TBI and BAD final D value demonstrated the
      highest AUC (0.925 and 0.786, respectively) and pAUC (0.150 and 0.088,
      respectively). TBI demonstrated 84.4% sensitivity and 82.4% specificity using a
      cut-off of 0.16. Comparative analysis between these parameters showed that AUC
      and pAUC of TBI were significantly higher than all parameters from Pentacam (P <=
      .032). CONCLUSIONS: In the current study, combined use of tomographic and
      biomechanical parameters demonstrated a higher capability in differentiating
      normal and SCKC eyes when compared to tomographic analysis alone. [J Refract
      Surg. 2018;34(9):616-621.].

PMID- 30199567
TI  - Influence of Microstructure on Stiffening Effects of Corneal Cross-linking
      Treatment.
AB  - PURPOSE: To investigate the stiffening effects of corneal cross-linking (CXL) on
      tensile properties of anterior and posterior corneal flaps. METHODS: A Descemet
      stripping automated endothelial keratoplasty system was used to prepare anterior
      and posterior flaps from porcine corneas. The flaps were subjected to CXL and
      their mechanical behavior was assessed by conducting uniaxial tensile
      experiments. Full-thickness corneas were also cross-linked from the posterior and
      anterior side and their tensile behavior was measured. RESULTS: The CXL procedure
      significantly improved biomechanical properties of anterior flaps (P < .05). CXL
      did not have any significant effect on tensile properties of posterior flaps.
      Cross-linking full-thickness porcine corneal stroma from the posterior side had
      no significant stiffening effect. CONCLUSIONS: The stiffening effect of CXL
      therapy depends significantly on the composition and microstructure of corneal
      extracellular matrix. [J Refract Surg. 2018;34(9):622-627.].

PMID- 30199568
TI  - Binocular and Monocular Implantation of Small-Aperture Intraocular Lenses in
      Cataract Surgery.
AB  - PURPOSE: To compare the clinical outcomes with the extended depth of focus small
      aperture intraocular lens (IOL) (IC-8; AcuFocus, Irvine, CA) for presbyopia
      compensation when implanted monocularly or binocularly. METHODS: Visual outcomes,
      defocus curve, patient satisfaction, and visual symptoms during a 6-month follow
      up were evaluated in 11 patients (contralateral group) implanted monocularly with
      this IOL and with an aspheric monofocal IOL in the fellow eye (myopic target) and
      6 patients (bilateral group) implanted bilaterally with the IC-8 IOL (dominant
      eye with plano target, fellow eye with myopic target). RESULTS: Bilateral
      implantation of the IC-8 IOL resulted in an extended range of focus, with better
      intermediate and near vision. Monocular implantation of the IC-8 IOL resulted in
      a significantly higher overall satisfaction score and lower halo score.
      CONCLUSIONS: Bilateral implantation of the IC-8 IOL resulted in an extended range
      of focus, with better intermediate and near vision than monocular implantation of
      this IOL. [J Refract Surg. 2018;34(9):629-631.].

PMID- 30199570
TI  - Pupillometry After Implantation of Phakic Intraocular Lens.

PMID- 30199571
TI  - Improved Accuracy With a Vergence-Based Online Toric Intraocular Lens Back
      calculator.

PMID- 30199572
TI  - Acute-on-Chronic Liver Failure defined by NACSELD: The Impact on Prognosis and
      Futility of Care.

PMID- 30199573
TI  - Vaginal cuff dehiscence is observed in a higher rate after total laparoscopic
      hysterectomy compared with other types of hysterectomy.
AB  - INTRODUCTION: Recently, it has been suggested that the occurrence of
      posthysterectomy vaginal cuff dehiscence has increased. Consequently, we
      evaluated the incidence of vaginal cuff dehiscence after different types of
      hysterectomies. Our hypothesis is that vaginal cuff dehiscence is more often
      associated with total laparoscopic hysterectomy (TLH) than other types of uterine
      removal. MATERIAL AND METHODS: A total of 13 645 hysterectomies from 1992 to 2015
      were evaluated in the Turku University Hospital district, Finland. The primary
      outcome was occurrence of vaginal dehiscence after different types of
      hysterectomy. The hysterectomy and postoperative vaginal dehiscence trends were
      analyzed as the secondary outcome. In a subanalysis of dehiscence cases, women's
      characteristics and perioperative vaginal cuff opening and closure techniques
      were compared between conventional hysterectomies (vaginal, abdominal, and
      laparoscopic with vaginal closure) and TLH. RESULTS: Altogether, 22 cases of
      vaginal cuff dehiscence were included. Most cases (n = 15) occurred after TLH (n
      = 1104), resulting in an incidence of 1.27%. After conventional laparoscopic
      hysterectomy with vaginal closure (n = 2853), vaginal (n = 4150), and abdominal
      (n = 5538) hysterectomies, the incidence rates were 0.11%, 0.05%, and 0.02%,
      respectively. Compared to abdominal hysterectomy, which was associated with the
      lowest incidence rate, vaginal dehiscence after TLH had an odds ratio (OR) 71.1
      (9.34-541.38, P < 0.001). In the subanalysis of possible underlying factors, the
      technique of opening of the vaginal cuff with or without electrocoagulation,
      duration of operation, and occurrence of postoperative infection or hematoma
      prior to VCD were observed differences between TLH and conventional
      hysterectomies. CONCLUSIONS: Compared with other types of hysterectomies, vaginal
      dehiscence was observed at the highest rate after TLH. Studies are needed to
      define if vaginal opening technique contributes to the risk of dehiscence.

PMID- 30199569
TI  - Bilateral Non-tuberculous Mycobacterial Keratitis After Small Incision Lenticule
      Extraction.
AB  - PURPOSE: To report a case of bilateral non-tuberculous mycobacterial keratitis
      after small incision lenticule extraction (SMILE) that was successfully treated
      with oral and topical fortified antibiotics. METHODS: Case report and literature
      review. RESULTS: An otherwise healthy 21-year-old woman presented with culture
      proven bilateral Mycobacterium abscessus keratitis 8 days after undergoing SMILE,
      showing multiple white stromal infiltrates in the interface in both eyes.
      Progressive, diffuse flap edema followed by pocket abscess, exudation in the
      anterior chamber, granulation tissue formation in the pocket, intrastromal
      neovascularization, and eventually partial resolution of corneal opacity were
      noted after topical and oral antibiotic treatment for 6 months. Her corrected
      distance visual acuity was 20/32 and 20/50 in the right and left eyes,
      respectively, 12 months after initial presentation. CONCLUSIONS: This is the
      first report of successful medical management of bilateral non-tuberculous
      mycobacterial keratitis after SMILE. The manifestations are different from and
      even more difficult to treat than those of keratitis after LASIK. [J Refract
      Surg. 2018;34(9):633-636.].

PMID- 30199574
TI  - Recurrence rates of cutaneous squamous cell carcinoma of the head and neck after
      Mohs micrographic surgery vs. standard excision: a retrospective cohort study.
AB  - BACKGROUND: Recurrent cutaneous squamous cell carcinoma (cSCC) has been
      associated with an increased risk of local functional and aesthetic comorbidity,
      metastasis and mortality. OBJECTIVES: To compare the risk of recurrence between
      Mohs micrographic surgery (MMS) and standard excision for cSCC of the head and
      neck. METHODS: This was a retrospective cohort study of all patients with a cSCC
      treated with MMS or standard excision at the departments of dermatology of a
      secondary or tertiary care hospital in the Netherlands between 2003 and 2012. To
      detect all recurrences, patients were linked to the Dutch pathology registry. To
      compare the risk of recurrence between MMS and standard excision, hazard ratios
      (HRs) were used adjusted for clinical tumour size > 2 cm and deep tumour
      invasion. RESULTS: A total of 579 patients with 672 cSCCs were included: 380
      cSCCs were treated with MMS and 292 with standard excision. The risk of
      recurrence was 8% (22 of 292) after standard excision during a median follow-up
      of 5.7 years [interquartile range (IQR) 3.5-7.8], which was higher than the 3%
      (12 of 380) after MMS during a median follow-up of 4.9 years (IQR 2.3-6.0). The
      cumulative incidence of recurrence was higher for standard excision than for MMS
      during the entire follow-up period of 8.6 years. Carcinomas treated with MMS were
      at a three times lower risk of recurrence than those treated with standard
      excision when adjusted for tumour size and deep tumour invasion (adjusted HR
      0.31, 95% confidence interval 0.12-0.66). CONCLUSIONS: MMS might be superior to
      standard excision for cSCCs of the head and neck because of a lower rate of
      recurrence.

PMID- 30199575
TI  - Partners under pressure: humanitarian action for the Syria crisis.
AB  - Partnerships between organisations in humanitarian crisis situations generally
      are challenging, but at the apex are those established as part of remote
      management in a context of extreme insecurity. To date, little systematic
      research has been conducted on arrangements between local organisations that have
      access to crisis-affected populations and international organisations that hold
      the purse strings. This paper presents the findings of nine months of qualitative
      research conducted with five Syrian local organisations and their international
      partners engaging in humanitarian action across the Turkey-Syria border, and
      presents insights into the components of successful partnerships. It redefines
      capacity along organisational and operational lines, and unpacks how monitoring
      and evaluation and donor requirements create tension and, at times, place local
      organisations at risk. The paper highlights the centrality of trust in successful
      partnerships, and describes the personalisation of the conflict by local
      organisations. Based on a historical case study of civil society in northern
      Iraq, it closes with some suggestions for long-term sustainability.

PMID- 30199577
TI  - Reply.

PMID- 30199576
TI  - A novel lncRNA regulates HCV infection through IFI6.
AB  - BACKGROUND AND AIMS: Long non-coding RNAs (lncRNAs) play a critical role in the
      regulation of many important cellular processes. However, the mechanisms by which
      lncRNAs regulate viral infection and host immune responses are not well
      understood. We sought to explore lncRNA regulation of HCV infection and
      interferon response. METHODS: We performed RNAseq in Huh7.5.1 cells with or
      without IFNalpha treatment. CRISPR/Cas9 guide RNA (gRNA) was used to knock out
      selected genes. The promoter clones were constructed, and the activity of related
      interferon-stimulated genes (ISGs) were detected by the secrete-pair dual
      luminescence assay. We constructed the full-length and four deletion mutants of
      an interferon-induced lncRNA RP11-288L9.4 (lncRNA-IFI6) based on predicted
      secondary structure. Selected gene mRNAs and their proteins, together with HCV
      infection, in Huh7.5.1 cells and Primary Human Hepatocytes (PHHs) were monitored
      by qRT-PCR and Western blot. RESULTS: We obtained 7901 lncRNAs from RNAseq. 1062
      host-encoded lncRNAs were significantly differentially regulated by IFNalpha
      treatment. We found that lncRNA-IFI6 gRNA significantly inhibited HCV infection
      compared to negative gRNA control. The expression of the antiviral ISG IFI6 was
      significantly increased following lncRNA-IFI6 gRNA editing compared to negative
      gRNA control in JFH1-infected Huh7.5.1 cells and PHHs. We observed that lncRNA
      IFI6 regulation of HCV was independent of JAK-STAT signaling. lncRNA-IFI6
      negatively regulated IFI6 promoter function through histone modification.
      Overexpression of the truncated spatial domain or full-length lncRNA-IFI6
      inhibited IFI6 expression and increased HCV replication. CONCLUSION: A novel
      lncRNA, lncRNA-IFI6, regulates antiviral innate immunity in the JFH1 HCV
      infection model. lncRNA-IFI6 regulates HCV infection independently of the JAK
      STAT pathway. lncRNA-IFI6 exerts its regulatory function via promoter activation
      and histone modification of IFI6 through its spatial domain. This article is
      protected by copyright. All rights reserved.

PMID- 30199578
TI  - Successful treatment of metastatic mucosal melanoma with a Del579 c-KIT mutation
      by imatinib after treatment of anti-PD-1 antibody.

PMID- 30199579
TI  - HBV seroprevalence after 25 years of universal mass vaccination and management of
      non-responders to the anti-Hepatitis B vaccine: An Italian study among medical
      students.
AB  - According to international guidelines, healthcare workers and medical students
      immunized against HBV are periodically tested for anti-HBs IgG. Subjects who show
      an anti-HBs titre <10 mUI/mL must receive additional vaccine doses to induce a
      measurable antibody response. This study aimed to evaluate the long-time
      immunogenicity of anti-hepatitis B vaccination in a sample of medical students
      and residents of the University of Bari who attended the Hygiene Department for
      biological risk assessment (April 2014-June 2017). The strategy for the
      management of nonresponder subjects was evaluated. A total of 3676 students and
      residents were invited for testing according to a standardized protocol. Anti-HBs
      IgG was tested for in 3140 (85.4%) subjects: 1174/3140 (37.7%) subjects were
      negative. 14.6% (128/808) of subjects who received the vaccine during their 12th
      year of life and 45.8% (1056/2305) of subjects immunized during the first year of
      life (P < 0.0001) were negative. 1005/1174 (85.6%) seronegative subjects received
      a booster dose, and 903/1005 (89.9%) were tested for anti-HBs 1 month after the
      booster dose: 82/903 (9.1%) subjects were still negative. Of these, 56/82 (68.3%)
      received 2 additional doses of vaccine and 52/56 (92.9%) were tested 1 month
      after the third dose: 50/52 subjects (96.2%) developed a positive titre. In
      conclusion, several medical students, immunized at birth or at young age against
      HBV, did not develop protective titres against the virus. Our management strategy
      (booster retest; for negative subjects, 2 doses and retest) seems consistent with
      the purpose of evidencing immunological memory.

PMID- 30199580
TI  - Chemical and Biochemical Strategies To Explore the Substrate Recognition of O
      GlcNAc-Cycling Enzymes.
AB  - The O-linked N-acetylglucosamine (O-GlcNAc) modification is an essential
      component in cell regulation. A single pair of human enzymes conducts this
      modification dynamically on a broad variety of proteins: O-GlcNAc transferase
      (OGT) adds the GlcNAc residue and O-GlcNAcase (OGA) hydrolyzes it. This
      modification is dysregulated in many diseases, but its exact effect on particular
      substrates remains unclear. In addition, no apparent sequence motif has been
      found in the modified proteins, and the factors controlling the substrate
      specificity of OGT and OGA are largely unknown. In this minireview, we will
      discuss recent developments in chemical and biochemical methods toward addressing
      the challenge of OGT and OGA substrate recognition. We hope that the new concepts
      and knowledge from these studies will promote research in this area to advance
      understanding of O-GlcNAc regulation in health and disease.

PMID- 30199581
TI  - Standardizing the evaluation of community-based conservation success.
AB  - Community-based conservation, which strives to simultaneously improve nature
      conservation and alleviate poverty, must provide biological and socioeconomic
      benefits that are linked through effective resilience mechanisms. To date, few
      community-based conservation initiatives have published comprehensive assessments
      that track performance in these elements of success. With 45% of the world's
      protected areas in comanagement with local communities, standardized measures to
      effectively evaluate the dual goals of community-based conservation are needed.
      We here introduce SPECCS, a user-friendly Standardized Protocol for Evaluating
      Community Conservation Success that incorporates an appraisal of data quality to
      responsibly assess progress over time or to compare effectiveness among different
      initiatives. We illustrate SPECCS's use by evaluating the Wechiau Community Hippo
      Sanctuary (WCHS) of northern Ghana 10 and 20 yr after its inception. The WCHS has
      the dual objective of protecting one of Ghana's few remaining hippopotamus
      populations while alleviating poverty in the surrounding communities through the
      creation of economic opportunity and infrastructure development. Results suggest
      stable project performance in the 10-yr (76%) and 20-yr (76%) evaluation, with an
      improvement in evaluation quality from 30% to 34%. The project is currently
      stronger in socioeconomic (performance 86%; quality 30%) than biological (60%;
      32%) outcomes and in benefits (83%, 42%) than resilience (63%, 21%). Biological
      resilience is challenged by poor connectivity and limited project control over
      threats, whereas socioeconomic resilience is affected by a decision balance that
      continues to favor external stakeholders. SPECCS helps pinpoint strengths and
      weaknesses for timely adaptive management, strategic investments, and evidence
      based recognition of community-based conservation successes.

PMID- 30199582
TI  - Glucocorticoids ameliorate periostin-induced tissue remodeling in chronic
      rhinosinusitis with nasal polyps.
AB  - BACKGROUND: Periostin plays an important role in the development of chronic
      rhinosinusitis (CRS) with nasal polyps (CRSwNP). Glucocorticoids (GCs) are anti
      inflammatory drugs used to treat CRS, but the mechanism for inhibiting periostin
      induced tissue remodeling is still unclear. We sought to investigate the
      expression of periostin, alpha-SMA, and extracellular matrix (ECM) components in
      sinonasal tissues and to evaluate the inhibitory mechanism of GCs in nasal
      fibroblasts and mucosa. METHODS: We measured the expression of periostin, alpha
      SMA and ECM components in sinonasal tissues. Correlation of CRS severity and
      periostin was evaluated by the Lund-Mackey score. Fibroblasts and ex vivo culture
      of the inferior turbinate were used to investigate the effects of GCs on
      periostin-induced alterations using real-time PCR, western blot, and
      immunostaining. Wound healing, transwell invasion, and collagen gel contraction
      were performed to evaluate migration and collagen contraction. RESULTS: Periostin
      was highly expressed in eosinophilic CRSwNP and correlated with the Lund-Mackay
      score. In nasal fibroblasts, periostin increased tissue remodeling involved
      protein. GCs suppressed the alterations of periostin. In addition, periostin
      induced activation of Src/AKT/mTOR, which was inhibited by GCs. GCs also
      inhibited periostin-induced migration, invasion, and collagen gel contraction.
      CONCLUSION: We suggest that GCs are therapeutic agents for CRSwNP by inhibiting
      tissue remodeling through their inhibitory effect on Src/Akt/mTOR signaling
      pathway. This article is protected by copyright. All rights reserved.

PMID- 30199583
TI  - Analysis of novel missense ATR mutations reveals new splicing defects underlying
      Seckel syndrome.
AB  - Ataxia Telangiectasia and Rad3 related (ATR) is one of the main regulators of the
      DNA damage response. It coordinates cell cycle checkpoint activation, replication
      fork stability, restart and origin firing to maintain genome integrity. Mutations
      of the ATR gene have been reported in Seckel patients, who suffer from a rare
      genetic disease characterized by severe microcephaly and growth retardation.
      Here, we report the case of a Seckel patient with compound heterozygous mutations
      in ATR. One allele has an intronic mutation affecting splicing of neighboring
      exons, the other an exonic missense mutation, producing the variant p.Lys1665Asn,
      of unknown pathogenicity. We have modeled this novel missense mutation, as well
      as a previously described missense mutation p.Met1159Ile, and assessed their
      effect on ATR function. Interestingly, our data indicate that both missense
      mutations have no direct effect on protein function, but rather result in
      defective ATR splicing. These results emphasize the importance of splicing
      mutations in Seckel Syndrome.

PMID- 30199584
TI  - The impact of infection among left ventricular assist device recipients on post
      transplantation outcomes: A retrospective review.
AB  - INTRODUCTION: Left ventricular assist device (LVAD) infections are common, and
      the consequences of LVAD infections on orthotopic heart transplantation (OHT)
      outcomes are not well described. AIMS: The aim of this study was to describe
      clinical characteristics and evaluate risk factors for developing LVAD
      infections, and examine outcomes of LVAD-specific infections (VSI) after OHT.
      METHODS: We retrospectively investigated the records of 74 consecutive patients
      at two institutions who had undergone LVAD placement and subsequent OHT between
      January 2007 and December 2012. RESULTS: Forty-six of 74 (62%) LVAD recipients
      who underwent OHT had pre-transplant infections, and 18 (24%) had LVAD-specific
      infection (VSI), of which 71% were caused by gram-negative organisms. Of pre
      transplant non-LVAD infections, Clostridium difficile infection (CDI) was the
      most common (26%) followed by urinary tract infection (UTI, 16%) and pneumonia
      (PNA 15%). Univariate analysis comparing subjects with VSI to those without VSI
      showed a significant association with time spent outside the hospital prior to
      transplantation (median 231.8 days vs 142.2 days, P < 0.03) and total time
      between VAD placement and OHT (244.0 days and 150.5 days, P < 0.002). Logistic
      regression was performed and significant predictors for VAD-related infection
      were age and the presence of diabetes, with type of device as an effect modifier.
      Six months post-OHT survival was not significantly affected by the presence of
      VSI prior to transplant. There was a trend toward an association between the
      presence of any infection and post-transplant rejection (P < 0.09). There were 10
      post-transplant deaths by 6 months. Of these deaths, 4/10 (40%) were
      cardiopulmonary and 6/10 (60%) were related to infections. CONCLUSIONS: Advanced
      age and presence of diabetes were predictors of VSI, as well as type of VAD
      device, although device choice is likely affected by many clinical factors
      including age and comorbidities, as well as institution-specific preferences. VSI
      was not associated with a decrease in 6-month post-OHT survival. However,
      infections remain the major causes of death by 6 months post-transplant. Certain
      infections are associated with an increased risk of rejection, which merits
      further investigation.

PMID- 30199585
TI  - Rare-Earth Metal(II) Aryloxides: Structure, Synthesis, and EPR Spectroscopy of
      [K(2.2.2-cryptand)][Sc(OC6 H2 tBu2 -2,6-Me-4)3 ].
AB  - The suitability of aryloxide ligands for stabilizing +2 oxidation states of Sc
      and Y has been examined and EPR evidence indicating the first O-donor complexes
      of ScII and YII has been obtained, as well as an X-ray crystal structure of a
      ScII aryloxide complex. The trivalent rare-earth metal aryloxide precursors,
      Ln(OAr')3 , 1-Ln (Ln=Sc, Y, Gd, Dy, Ho, Er; OAr'=OC6 H2 tBu2 -2,6-Me-4), were
      synthesized from the corresponding rare-earth metal trichlorides and LiOAr'?OEt2
      . Reduction of THF solutions of 1-Ln with potassium graphite in the presence of
      2.2.2-cryptand (crypt) yielded dark-colored solutions, 2-Ln, whose EPR spectra at
      77 K are characteristic of the LnII ions: a two-line spectrum (g? =1.99, g?
      =1.97, Aave =154 G) for 2-Y and an eight-line spectrum (gave =2.01 and Aave =291
      G) for 2-Sc. Solutions of 2-Y decompose within one minute at room temperature,
      wheras 2-Sc persists up to 40 min at room temperature. 2-Sc was identified by X
      ray crystallography as [K(crypt)][Sc(OAr')3 ], which has a trigonal-planar
      arrangement of oxygen-donor atoms around ScII . Analogous reductions of 1-Ln for
      Ln=Gd, Dy, Ho, and Er also gave dark solutions of limited stability. Theoretical
      analysis using time-dependent density functional theory (TD-DFT) along with
      complete active space self-consistent field (CASSCF) methods, and structural
      analysis with the Guzei ligand solid angle G-parameter method are presented.

PMID- 30199586
TI  - Identification and molecular characterization of allergenic non-specific lipid
      transfer protein from durum wheat (Triticum turgidum).
AB  - BACKGROUND: Common wheat (Triticum aestivum) and durum wheat (T. turgidum) are
      both involved in Baker's asthma (BA) and food allergy (FA) including wheat
      dependent exercise-induced asthma (WDEIA). However, allergens in durum wheat have
      not been described, and the over-expression of T. turgidum non-specific lipid
      transfer protein (nsLTPs) is considered to increase resistance to phytopathogens.
      OBJECTIVE: To identify and assess the allergenicity of nsLTP from T. turgidum.
      METHODS: Recombinant T. turgidum nsLTP Tri tu 14 was generated and tested for
      structural integrity (circular dichroism-spectroscopy) and purity (SDS-PAGE).
      Thirty-two wheat allergic patients were enrolled: 20 Spanish patients (BA) with
      positive bronchial challenge to wheat flour, and 12 Italian patients (wheat
      FA/WDEIA) with positive double-blind placebo-controlled food challenge/open food
      challenge (OFC) to pasta. IgE values to wheat, Tri tu 14, Tri a 14 (T. aestivum)
      and Pru p 3 (P. persica) were determined by ImmunoCAP testing. Allergenic potency
      (in vitro mediator release) and IgE cross-reactivity were investigated. RESULTS:
      Tri tu 14 was found to share 49% and 52% amino acid identity with Tri a 14 and
      Pru p 3, respectively. Among 25 Tri a 14 CAP positive sera, 23 (92%) were
      reactive to wheat extract, 22 (88%) to Tri tu 14 and 20 (80%) to Pru p 3. The
      correlation between Tri a 14 and Tri tu 14 specific IgE levels was r = 0.97 (BA)
      and r = 0.93 (FA/WDEIA), respectively. FA/WDEIA patients showed higher specific
      IgE values to Tri tu 14 and Pru p 3 than BA patients. Tri tu 14 displayed
      allergenic activity by mediator release from effector cells and IgE cross
      reactivity with Pru p 3. The degree of IgE cross-reactivity between the two wheat
      nsLTPs varied between individual patients. CONCLUSIONS AND CLINICAL RELEVANCE:
      Sensitization to Tri tu 14 likely appears to be more important in wheat FA/WDEIA
      than in BA. Over-expression of Tri tu 14 in wheat would represent a risk for
      patients with nsLTP-mediated FA.

PMID- 30199587
TI  - Field evaluation of GeneXpert(r) (Cepheid) HCV performance for RNA quantification
      in a genotype 1 and 6 predominant patient population in Cambodia.
AB  - GeneXpert(r) (Cepheid) is the only WHO prequalified platform for hepatitis C
      virus (HCV) nucleic acid amplification testing that is suitable for point-of-care
      use in resource-limited contexts. However, its application is constrained by the
      lack of evidence on genotype 6 (GT6) HCV. We evaluated its field performance
      among a patient population in Cambodia predominantly infected with GT6. Between
      August and September 2017, we tested plasma samples obtained from consenting
      patients at Medecins Sans Frontieres' HCV clinic at Preah Kossamak Hospital for
      HCV viral load (VL) using GeneXpert(r) and compared its results to those obtained
      using COBAS(r) AmpliPrep/Cobas(r) TaqMan(r) HCV Quantitative Test, v2.0 (Roche)
      at the Institut Pasteur du Cambodge. Among 769 patients, 77% of the seropositive
      patients (n = 454/590) had detectable and quantifiable VL using Roche and 43% (n
      = 195/454) were GT6. The sensitivity and specificity of GeneXpert(r) against
      Roche were 100% (95% CI 99.2, 100.0) and 98.5% (95% CI 94.8, 99.8). The mean VL
      difference was -0.01 (95% CI -0.05, 0.02) log10  IU/mL for 454 samples
      quantifiable on Roche and -0.07 (95% CI -0.12, -0.02) log10  IU/mL for GT6 (n =
      195). The limit of agreement (LOA) was -0.76 to 0.73 log10  IU/mL for all GTs and
      -0.76 to 0.62 log10 IU/mL for GT6. Twenty-nine GeneXpert(r) results were outside
      the LOA. Frequency of error and the median turnaround time (TAT) for GeneXpert(r)
      were 1% and 0 days (4 days using Roche). We demonstrated that the GeneXpert(r)
      HCV assay has good sensitivity, specificity, quantitative agreement, and TAT in a
      real-world, resource-limited clinical setting among GT6 HCV patients.

PMID- 30199588
TI  - Ovulation induction strategies in polycystic ovary syndrome.

PMID- 30199589
TI  - The epidemiology of hepatitis B virus infection in China.

PMID- 30199590
TI  - Burnout symptoms in forensic psychiatric nurses and their associations with
      personality, emotional intelligence and client aggression: A cross-sectional
      study.
AB  - : WHAT IS KNOWN ON THE SUBJECT?: Client aggression in forensic psychiatry is
      associated with burnout symptoms in nursing staff. It is unclear what mechanisms
      contribute to this relationship. The type and severity of aggression might be of
      importance in the association between client aggression and burnout symptoms, but
      also the personality characteristics and emotional intelligence of nursing staff.
      It is unknown whether wearable devices that measure arousal can be used to detect
      chronic stress and burnout symptoms. WHAT DOES THIS PAPER ADD TO EXISTING
      KNOWLEDGE?: Especially, physical aggression as experienced by nursing staff is
      associated with staff's burnout symptoms (e.g., emotional exhaustion and
      depersonalization). Further research on the aggression questionnaire is
      necessary. The stress management skill of nursing staff is an important factor to
      consider in the association between burnout symptoms and client aggression. The
      wearable device was not useful for detecting burnout symptoms. WHAT ARE THE
      IMPLICATIONS FOR PRACTICE?: Nursing staff who experience (physical) aggression
      should be carefully monitored and should receive social support from their
      management to aid their well-being. Contrary to intuition, nurses who reported a
      higher number of stress management skills might have to be monitored more closely
      if necessary. ABSTRACT: Introduction Aggressive behaviour of forensic clients is
      associated with burnout symptoms in nursing staff. The role of staff
      characteristics as moderators is unclear. Aim We explored the association between
      type and severity of aggressive behaviour as experienced by nursing staff and
      staff's burnout symptoms. In addition, the moderating roles of personality
      characteristics and emotional intelligence (EI) were studied. Moreover, the
      usefulness of ambulatory skin conductance assessments in detecting arousal
      related to burnout symptoms was studied. Method A total of 114 forensic nursing
      staff members filled out questionnaires and wore an ambulatory device. Results
      Experiencing physical aggression was positively associated with staff's burnout
      symptoms. Stress management skills, a subscale of EI, but not personality,
      moderated this relationship. Skin conductance was not associated with burnout
      symptoms. Remarkably, the association between aggression and burnout symptoms was
      highest for staff reporting a higher number of stress management skills.
      Discussion Longitudinal research is necessary to establish causality between
      client aggression and staff burnout symptoms. In addition, further research is
      necessary on the validity of the aggression measure used in the current study.
      Implication for practice Nursing staff who experience physical aggression
      frequently should receive social support for this, and staff who report high
      stress management skills should be monitored more carefully after having been
      confronted with aggression.

PMID- 30199591
TI  - Origin and dissemination of hepatitis B virus genotype C in East Asia revealed by
      phylodynamic analysis and historical correlates.
AB  - Hepatitis B virus disease progression in East Asia is most frequently associated
      with genotype C (HBV/C). The increasing availability of HBV/C genetic sequences
      and detailed annotations provides an opportunity to investigate the
      epidemiological factors underlying its evolutionary history. In this study, the
      Bayesian phylogeography framework was used to investigate the origins and
      patterns in spatial dissemination of HBV/C by analyzing East Asian sequences
      obtained from 1992 to 2010. The most recent common ancestor of HBV/C was traced
      back to the early 1900s in China, where it eventually diverged into two major
      lineages during the 1930s-1960s that gave rise to distinct epidemic waves
      spreading exponentially to other East Asian countries and the USA. Demographic
      inference of viral effective population size over time indicated similar dynamics
      for both lineages, characterized by exponential growth since the early 1980s,
      followed by a significant bottleneck in 2003 and another increase after 2004.
      Although additional factors cannot be ruled out, we provide evidence to suggest
      this bottleneck was the result of limited human movement from/to China during the
      SARS outbreak in 2003. This is the first extensive evolutionary study of HBV/C in
      East Asia as well as the first to assess more realistic spatial ecological
      influences between co-circulating infectious diseases.

PMID- 30199592
TI  - Iridium alpha-Carboxyimine Complexes Hyperpolarized with para-Hydrogen Exist in
      Nuclear Singlet States before Conversion into Iridium Carbonates.
AB  - The formation and hyperpolarization of an [Ir(H)2 (amine)(IMes)(eta2 -imine)]Cl
      complex that can be created in a hyperpolarized nuclear singlet state is
      reported. These complexes are formed when an equilibrium mixture of pyruvate,
      amine (benzylamine or phenylethylamine), and the corresponding imine condensation
      product, react with preformed [Ir(H)2 (amine)3 (IMes)]Cl. These iridium alpha
      carboxyimine complexes exist as two regioisomers differentiated by the position
      of amine. When examined with para-hydrogen the hydride resonances of the isomer
      with amine trans to hydride become strongly hyperpolarized. The initial hydride
      singlet states readily transfer to the corresponding 13 C2 state in the labelled
      imine and exhibit magnetic state lifetimes of up to 11 seconds. Their 13 C
      signals have been detected with up to 420 fold signal gains at 9.4 T. On a longer
      timescale, and in the absence of H2 , further reaction leads to the formation of
      neutral carbonate containing [Ir(amine)(eta2 -CO3 )(IMes)(eta2 -imine)].
      Complexes are characterized by, IR, MS, NMR and X-ray diffraction.

PMID- 30199593
TI  - Early emergence of opportunistic infections after starting direct-acting
      antiviral drugs in HIV/HCV-coinfected patients.
AB  - Varicella-zoster virus and hepatitis B virus reactivations have been reported
      after starting interferon-free direct-acting antiviral agent (DAA) combinations.
      HIV/HCV-coinfected patients could be a high-risk group for the reactivation of
      latent infections. Because of these, we report the occurrence of severe
      infections after starting DAA regimens in HIV/HCV-coinfected patients.
      Individuals included in the HEPAVIR-DAA (NCT02057003) cohort were selected if
      they had received all-oral DAA combinations. A retrospective review of clinical
      events registered between the start of DAAs and 12 months after SVR12 was carried
      out. Overall, 38 (4.5%) of 848 patients presented infections. The incidence (95%
      confidence interval) of infections was 4.6 (3.3-6.3) cases per 100 person-years.
      The median (Q1-Q3) time to the infection since baseline was 23 (7.3-33) weeks.
      Five (13%) of the patients with infections died; four of them had cirrhosis. The
      frequency of previous AIDS was 21 (54%) for patients with infections and 324
      (40%) for those without infections (P = 0.084). The median (Q1-Q3) nadir CD4 cell
      count of individuals with and without infections was 75 (53-178) and 144 (67-255)
      cells/MUL, respectively (P = 0.047). Immunodepression-associated infections were
      observed in 9 (1.1%) patients. All of them had suppressed HIV replication with
      antiretroviral therapy. In conclusion, severe infections are relatively common
      among HIV/HCV-coinfected patients receiving all-oral DAA combinations. Some
      unusual reactivations of latent infections in patients with suppressed HIV
      replication seem to be temporally linked with DAA use.

PMID- 30199595
TI  - The paper that wrote itself-A ghost story.

PMID- 30199594
TI  - Topical and systemic antifungal therapy for chronic rhinosinusitis.
AB  - BACKGROUND: This review adds to a series of reviews looking at primary medical
      management options for patients with chronic rhinosinusitis.Chronic
      rhinosinusitis is common and characterised by inflammation of the lining of the
      nose and paranasal sinuses leading to nasal blockage, nasal discharge, facial
      pressure/pain and loss of sense of smell. The condition can occur with or without
      nasal polyps. Antifungals have been suggested as a treatment for chronic
      rhinosinusitis. OBJECTIVES: To assess the effects of systemic and topical
      antifungal agents in patients with chronic rhinosinusitis, including those with
      allergic fungal rhinosinusitis (AFRS) and, if possible, AFRS exclusively. SEARCH
      METHODS: The Cochrane ENT Information Specialist searched the Cochrane ENT Trials
      Register; Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE;
      Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional
      sources for published and unpublished trials. The date of the search was 17
      November 2017. SELECTION CRITERIA: Randomised controlled trials (RCTs) with at
      least a two-week follow-up period comparing topical or systemic antifungals with
      (a) placebo, (b) no treatment, (c) other pharmacological interventions or (d) a
      different antifungal agent. We did not include post-surgical antifungal use. DATA
      COLLECTION AND ANALYSIS: We used the standard Cochrane methodological procedures.
      Our primary outcomes were disease-specific health-related quality of life (HRQL),
      patient-reported disease severity and the significant adverse effects of hepatic
      toxicity (systemic antifungals). Secondary outcomes included general HRQL,
      endoscopic nasal polyp score, computerised tomography (CT) scan score and the
      adverse effects of gastrointestinal disturbance (systemic antifungals) and
      epistaxis, headache or local discomfort (topical antifungals). We used GRADE to
      assess the quality of the evidence for each outcome; this is indicated in
      italics. MAIN RESULTS: We included eight studies (490 adult participants). The
      presence of nasal polyps on examination was an inclusion criterion in three
      studies, an exclusion criterion in one study and the remaining studies included a
      mixed population. No studies specifically investigated the effect of antifungals
      in patients with AFRS.Topical antifungal treatment versus placebo or no
      interventionWe included seven studies (437 participants) that used amphotericin B
      (six studies; 383 participants) and one that used fluconazole (54 participants).
      Different delivery methods, volumes and concentrations were used.Four studies
      reported disease-specific health-related quality of life using a range of
      instruments. We did not meta-analyse the results due to differences in the
      instruments used, and measurement and reporting methods. At the end of treatment
      (one to six months) none of the studies reported statistically significant
      differences between the groups (low-quality evidence - we are uncertain about the
      result).Two studies reported disease severity using patient-reported symptom
      scores. Meta-analysis was not possible. At the end of treatment (8 to 13 weeks)
      one study showed no difference and the second found that patients in the placebo
      group had less severe symptoms (very low-quality evidence - we are very uncertain
      about the result).In terms of adverse effects, topical antifungals may lead to
      more local irritation compared with placebo (risk ratio (RR) 2.29, 95% confidence
      interval (CI) 0.61 to 8.62; 312 participants; 5 studies; low-quality evidence)
      but little or no difference in epistaxis (RR 0.97, 95% CI 0.14 to 6.63; 225
      participants; 4 studies, low-quality evidence) or headache (RR 1.26, 95% CI 0.60
      to 2.63; 195 participants; 3 studies; very low-quality evidence).None of the
      studies found a difference in generic health-related quality of life (one study)
      or endoscopic score (five studies) between the treatment groups. Three studies
      investigated CT scan; two found no difference between the groups and one found a
      significant decrease in the mean percentage of air space occluded, favouring the
      antifungal group.Systemic antifungal treatment versus placebo or no treatmentOne
      study (53 participants) comparing terbinafine tablets against placebo reported
      that there may be little or no difference between the groups in disease-specific
      health-related quality of life or disease severity score (both low-quality
      evidence). Systemic antifungals may lead to more hepatic toxicity events (RR
      3.35, 95% CI 0.14 to 78.60) but fewer gastrointestinal disturbances (RR 0.37, 95%
      CI 0.04 to 3.36), compared to placebo, although the evidence was of low
      quality.This study did not find a difference in CT scan score between the groups.
      Generic health-related quality of life and endoscopic score were not
      measured.Other comparisonsWe found no studies that compared antifungal agents
      against other treatments for chronic rhinosinusitis. AUTHORS' CONCLUSIONS: Due to
      the very low quality of the evidence, it is uncertain whether or not the use of
      topical or systemic antifungals has an impact on patient outcomes in adults with
      chronic rhinosinusitis compared with placebo or no treatment. Studies including
      specific subgroups (i.e. AFRS) are lacking.

PMID- 30199597
TI  - Physicochemical and biological properties of novel chlorhexidine-loaded nanotube
      modified dentin adhesive.
AB  - A commercially available three-step (etch-and-rinse) adhesive was modified by
      adding chlorhexidine (CHX)-loaded nanotubes (Halloysite(r), HNT) at two
      concentrations (CHX10% and CHX20%). The experimental groups were: SBMP
      (unmodified adhesive, control), HNT (SBMP modified with HNT), CHX10 (SBMP
      modified with HNT loaded with CHX10%), and CHX20 (SBMP modified with HNT loaded
      with CHX20%). Changes in the degree of conversion (DC%), Knoop hardness (KHN),
      water sorption (WS), solubility (SL), antimicrobial activity, cytotoxicity, and
      anti-matrix metalloproteinase [MMP-1] activity (collagenase-I) were evaluated. In
      regards to DC%, two-way ANOVA followed by Tukey's post-hoc test revealed that
      only the factor "adhesive" was statistically significant (p < 0.05). No
      significant differences were detected in DC% when 20 s light-curing was used (p >
      0.05). For Knoop microhardness, one-way ANOVA followed by the Tukey's test showed
      statistically significant differences when comparing HNT (20.82 +/- 1.65) and
      CHX20% (21.71 +/- 2.83) with the SBMP and CHX10% groups. All adhesives presented
      similar WS and cytocompatibility. The CHX-loaded nanotube-modified adhesive
      released enough CHX to inhibit the growth of S. mutans and L. casei. Adhesive
      eluates were not able to effectively inhibit MMP-1 activity. The evaluation of
      higher CHX concentrations might be necessary to provide an effective and
      predictable MMP inhibition. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res B
      Part B, 2018.

PMID- 30199596
TI  - Structural Elucidation of Trace Components Combining GC/MS, GC/IR, DFT
      Calculation and Synthesis-Salinilactones, Unprecedented Bicyclic Lactones from
      Salinispora Bacteria.
AB  - The analysis of volatiles released by marine Salinispora bacteria uncovered a new
      class of natural compounds displaying an unusual bicyclic [3.1.0]-lactone
      skeleton. Although only sub-MUg quantities of the compounds were available, the
      combination of analytical methods, computational spectroscopy, and synthesis
      allowed unambiguous structural identification of the compounds, called
      salinilactones, without the need for isolation. Orthogonal hyphenated methods,
      GC/MS and solid-phase GC/IR allowed to propose a small set of structures
      consistent with the data. A candidate structure was selected by comparison of DFT
      calculated IR spectra and the experimental IR-spectrum. Synthesis confirmed the
      structure and absolute configuration of three bicyclic lactones, salinilactones A
      C. The salinilactones are structurally closely related to the A-factor class of
      compounds, autoregulators from streptomycete bacteria. They exhibited inhibitory
      activity against Salinispora and Streptomyces strains.

PMID- 30199598
TI  - Human papillomavirus infection and colorectal cancer in the Chinese population: a
      meta-analysis.
AB  - AIM: Human papillomavirus (HPV) infection has been reported in colorectal cancer
      in many studies. We conducted a meta-analysis to assess the association between
      HPV infection and colorectal cancer/adenomas in the Chinese population. METHOD:
      Relevant studies up to January 2018 were searched in PubMed, EMBASE, China
      National Knowledge Infrastructure and the Wanfang database. We used a random
      effects model to determine the prevalence of HPV and odds ratios (ORs) with 95%
      confidence intervals (CIs). The I2 statistic and P-value from the Cochrane Q-test
      were used to describe the heterogeneity. RESULTS: Ten case-control studies
      involving 766 colorectal cancer patients and 470 controls were included in the
      meta-analysis. Among the colorectal cancer patients, the pooled prevalence was
      0.45 (95% CI 0.36-0.53). The pooled estimate for OR was 10.78 (95% CI 4.22,
      27.53). Among the 193 patients with colorectal adenoma, the pooled prevalence and
      OR were 0.31 (95% CI 0.24-0.37) and 2.03 (95% CI 0.79, 5.26), respectively. The
      prevalence of HPV 16 and HPV 18 among HPV-positive cancers ranged from 57.9% to
      100% and 0% to 39.7%, respectively. CONCLUSION: The results indicated that HPV
      infection, especially HPV 16 and HPV 18, is associated with colorectal cancer in
      the Chinese population.

PMID- 30199599
TI  - A novel method for continuous formation of cord-like collagen gels to fabricate
      durable fibers in which collagen fibrils are longitudinally aligned.
AB  - We developed a continuous formation method of cord-like collagen gels comprising
      fibrils preferentially aligned along the geometrical axes (CCGs). Collagen (2.5%)
      dissolved in a sodium phosphate buffer containing 280 mM of sodium chloride was
      introduced into a stainless cylinder (length 52 mm, diameter 2.0 mm) warmed at 38
      degrees C at a linear velocity of 2.5 mm/s. This process caused collagen fibril
      alignments under acute fibril formation in the cylinder, resulting in continuous
      formation of CCGs. Fibril formation rate, shear rate, and shear duration were
      substantial factors for successful CCG formation. Outstanding advantages of this
      method over conventional wet spinning include the capacity of this technique to
      form aligned fibrils in the entire gels and to control the diameter of cord-like
      gels over 1 mm. The air-drying of CCGs which were crosslinked with 1-ethyl-3-(3
      dimethylaminopropyl)-carbodiimide and N-hydroxy-succinimide produced dry collagen
      fibers with cross-sectional areas of 0.0123-0.135 mm2 . Upon the rewetting of the
      fibers, they failed at a stress of 54.5 +/- 7.8 MPa, which is higher than the
      mean failure stress of anterior cruciate ligament tissue (13.3-37.8 MPa). These
      findings indicate that the CCG formation method enables the fabrication of
      collagen fibers which are potential components of collagen-based artificial
      tendons. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res B Part B: Appl
      Biomater, 2018.

PMID- 30199600
TI  - The effect of collector type on the physical, chemical, and biological properties
      of polycaprolactone/gelatin/nano-hydroxyapatite electrospun scaffold.
AB  - Electrospinning is considered a powerful method for the production of fibers in
      the nanoscale size. Small pore size results in poor cell infiltration, cell
      migration inhibition into scaffold pores and low oxygen diffusion. Electrospun
      polycaprolactone/gelatin/nano-hydroxyapatite (PCL/Gel/nHA) scaffolds were
      deposited into two types of fiber collectors (novel rotating disc and plate) to
      study fiber morphology, chemical, mechanical, hydrophilic, and biodegradation
      properties between each other. The proliferation and differentiation of MG-63
      cells into the bone phenotype were determined using MTT method, alizarin red
      staining and alkaline phosphatase (ALP) activity. The rates for disc rotation
      were 50 and 100 rpm. The pore size measurement results indicated that the fibers
      produced by the disc rotation collector with speed rate 50 rpm have larger pores
      as compared to fibers produced by disc rotation at 100 rpm and flat plate
      collectors. A randomly structure with controlled pore size (38.65 +/-0.33 MUm)
      and lower fiber density, as compared to fibers collected by disc rotation with
      speed rate 100 rpm and flat plate collectors, was obtained. Fibers collected on
      the rotating disc with speed rate 50 rpm, were more hydrophilic due to larger
      pore size and therefore, faster infiltration of water into the scaffold and the
      rate of degradation was higher. These results demonstrate that PCL/Gel/nHA
      scaffolds made through a rotating disc collector at 50 rpm are more feasible to
      be used in bone tissue engineering applications due to appropriate pore size and
      increased adhesion and proliferation of cells, ALP activity and mineral deposits.

PMID- 30199601
TI  - Sol-gel bioglasses in dental and periodontal regeneration: A systematic review.
AB  - Due to their osteoconductive and osteoinductive abilities, bioglasses (BGs) have
      attracted attention in tissue engineering, especially for mineralized tissue. The
      aim of this study is to review the current state of the art on the effects of BGs
      produced by sol-gel on cells for dental and periodontal regeneration. The study
      also discusses associated antibacterial properties. The research was performed by
      considering the Preferred Reporting Items for Systematic Reviews and the Meta
      Analyses (PRISMA) statement. The research ranged 5 years' window time (from
      January, 01, 2012, to August, 31, 2017) and the relevant studies were identified
      based on the inclusion/exclusion criteria. A total of 45 articles were selected
      from 244 initial returns, plus seven further articles coming from other sources
      were selected for the same purpose. From this systematic study, it is revealed
      that only 13 of the 52 articles have proved both the ability of BGs to
      differentiate dental cells at genetic level and their ability of triggering cell
      mediated mineralization, but only six of them showed, along with cells, the
      antibacterial properties of the glasses. This review shows that sol-gel BGs are
      not toxic, can sustain cell proliferation and differentiation at a genetic level,
      and can keep the bacterial population under control. Moreover, a standard
      methodology and an ideal material are suggested. (c) 2018 Wiley Periodicals, Inc.
      J. Biomed. Mater. Res. Part B, 2018.

PMID- 30199602
TI  - Successful bony integration of a porous tantalum implant despite longlasting and
      ongoing infection: Histologic workup of an explanted shoulder prosthesis.
AB  - Infection associated with an implant is a complication feared in surgery, as it
      leads to loosening and dysfunction. This report documents an unexpected good bony
      integration of a porous tantalum shoulder prosthesis despite infection. A
      shoulder prosthesis with a porous tantalum glenoidal base plate was retrieved
      after 3 years of ongoing infection with Staphylococcus spp. Methyl-methacrylate
      embedded sections of the retrieved glenoidal component were analyzed by optical
      and scanning electron beam microscopy (SEM). Bone ongrowth and ingrowth were
      quantified. Bone had formed at the implant surface and within the open cell
      structure of the porous tantalum. The bone implant contact index was 32%. The
      bone ingrowth or relative bone area within the open structure was 8.2%,
      respectively 11.9% in the outer 50% of the thickness. Due to the section
      thickness, bone ongrowth could best be documented in SEM. Despite long-lasting
      and ongoing infection, the glenoidal base plate of the prosthesis showed good
      bony integration upon removal. The bone ingrowth into the porous tantalum was
      comparable to the values previously reported for the undersurface of retrieved
      proximal humerus resurfacing implants. Good integration of the implant however
      did not solve the problem of infection, and related morbidity. (c) 2018 Wiley
      Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2924-2931,
      2018.

PMID- 30199603
TI  - In vivo evaluation of resorbable supercritical CO2 -treated collagen membranes
      for class III furcation-guided tissue regeneration.
AB  - The study evaluated the effects of a Supercritical CO2 (scCO2 ) on a commercially
      available decellularized/delipidized naturally derived porcine pericardium
      collagen membrane, Vitala(r). The Vitala(r) and scCO2 treated experimental
      membranes were evaluated for guided tissue regeneration (GTR) of periodontal
      tissue in class III furcation defects utilizing a dog model. Physical material
      characterization was performed by scanning electron microscopy (SEM),
      thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC).
      The in vivo portion of the study was allocated to three-time points (6, 12, and
      24-weeks) using standardized class III furcation defects created in the upper
      second and third premolars. The experimental defects (n = 5) were covered with
      either a collagen membrane (positive control), scCO2 -treated collagen membrane
      (experimental) or no membrane (negative control). Following sacrifice, histologic
      serial sections were performed from cervical to apical for
      morphologic/morphometric evaluation. Morphometric evaluation was carried out by
      ranking the presence of collagen membrane, amount of bone formation within the
      defect site and inflammatory cell infiltrate content. SEM showed the experimental
      scCO2 -treated membrane to have a similar gross fibrous appearance and chemical
      structure in comparison to the Vitala(r) Collagen membrane. A significant
      increase in membrane thickness was noted in the scCO2 -treated membranes (366 +/-
      54 MUm) vs non-treated membranes (265 +/- 75 MUm). TGA and DSC spectra indicated
      no significant qualitative differences between the two membranes. For the in vivo
      results, both membranes indicated significantly greater amounts of newly formed
      bone (scCO2 : 2.85 +/- 1.1; Vitala(r): 2.80 +/- 1.0) within the covered defects
      relative to uncovered controls (0.8 +/- 0.27) at 24 weeks. Both membrane types
      gradually degraded as time elapsed in vivo from 6 to 12 weeks, and presented
      nearly complete resorption at 24 weeks. The inflammatory infiltrate at regions in
      proximity with the membranes was commensurate with healthy tissue levels from 6
      weeks in vivo on, and periodontal ligament regeneration onset was detected at 12
      weeks in vivo. The effect of the supplementary scCO2 treatment step on the
      collagen membrane was demonstrated to be biocompatible, allowing for the
      infiltration of cells and degradation over time. The treated membranes presented
      similar performance in GTR to non-treated samples in Class III furcation lesions.
      Defects treated without membranes failed to achieve regeneration of the native
      periodontium. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res B Part B: Appl
      Biomater 00B: 000-000, 2018.

PMID- 30199604
TI  - Simultaneous transcriptome and proteome analysis of EA.hy926 cells under stress
      conditions induced by nanomaterials.
AB  - Today, the extensive and constantly growing number of applications in the field
      of nanotechnology poses a lot of questions about the potential toxicity of
      nanomaterials (NMs) toward cells of different origins. In our work we employed
      the tools of molecular biology to evaluate changes that occur in human
      endothelial cells at the transcriptomic and proteomic level, following 24 h of
      exposure to three different classes of NMs. Using microarray technology, we
      demonstrated that 24 h of exposure to silver nanoparticles (SNPs), multiwalled
      carbon nanotubes (MWCNTs) and polyamidoamine dendrimers (PAMAMs) leads to changes
      in 299, 1271, and 431 genes, respectively, influencing specific molecular
      pathways. The 2D-DIGE and mass spectrometry analysis revealed that differentially
      expressed proteins were involved in numerous cellular processes, for example,
      cytoskeletal reorganization, cell growth and proliferation, or response to
      stress. Both, transcriptome and proteome alterations indicate reorganization of
      mechanism regulating cell functioning. (c) 2018 Wiley Periodicals, Inc. J Biomed
      Mater Res B Part B: Appl Biomater, 2018.

PMID- 30199605
TI  - Advances and challenges in targeting IRF5, a key regulator of inflammation.
AB  - Interferon regulatory factor 5 (IRF5) belongs to a family of transcription
      factors, originally implicated in antiviral responses and interferon production.
      However, studies conducted in different laboratories over the last decade have
      placed IRF5 as a central regulator of the inflammatory response. It has become
      clear that IRF5 contributes to the pathogenesis of many inflammatory and
      autoimmune diseases, such as rheumatoid arthritis, inflammatory bowel disease and
      systemic lupus erythematosus. Given the role of IRF5 in physiology and disease,
      IRF5 represents a potential therapeutic target. However, despite a significant
      interest from the pharmaceutical industry, inhibitors that interfere with the
      IRF5 pathway remain elusive. Here, we review the advances made by various studies
      in targeting multiple steps of signalling leading to IRF5 activation with their
      therapeutic potential, and the possible complications of such strategies are
      discussed.

PMID- 30199606
TI  - Advancement flap procedure in Crohn and non-Crohn perineal fistulas: a simple
      surgical approach.
AB  - AIM: Rectal flap advancement is still a part of therapeutic management of anal
      fistulas. Data on the outcome of rectal flap advancement in patients with Crohn's
      disease (CD) is scarce. Our objective was to ascertain rates of failure of rectal
      flap advancement and to determine predictive factors for failure, with a special
      focus on CD METHOD: The patients' details, the characteristics of the fistula and
      the main clinical and therapeutic events were prospectively assessed among
      patients who underwent rectal flap advancement. All patients had a partial
      thickness rectal flap advancement. Failure of primary rectal flap advancement was
      defined as the occurrence of at least one of the following: abscess, discharge,
      visible external opening, further drainage procedure. The rates of failure of
      rectal flap and the predictive factors of failure were assessed. RESULTS: Eighty
      seven patients (34 patients with CD) were included. The median (interquartile
      range) follow-up was 13.3 (3.8-38.1) months. The cumulative failure rates were
      15.9% (10.3-23.6), 23.0% (16.0-31.8), 31.6% (22.9-41.8) and 41.3% (30.5-53.0) at
      3, 6, 12 and 24 months respectively. These data were comparable in Crohn's
      patients. Those with a supralevator fistula [hazard ratio 2.53 (1.01-7.71), P =
      0.0476] and patients who had fewer than two fistula drainages before rectal flap
      [hazard ratio 3.19 (1.40-8.23), P = 0.005] were associated with higher rectal
      flap failure rates. In CD patients, the absence of biological therapy at referral
      was predictive of failure. CONCLUSION: Rectal flap advancement is a satisfactory
      option for the therapeutic management of anal fistula, including CD populations.
      Fistula drainage is needed before performing this surgical technique.

PMID- 30199608
TI  - Colorectal surgery and preoperative bowel preparation: aren't we drawing hasty
      conclusions?

PMID- 30199607
TI  - Toe Walking Assessment in Autism Spectrum Disorder Subjects: A Systematic Review.
AB  - There is increasing evidence that autism spectrum disorder (ASD) subjects have
      also motor impairments. Toe walking (TW) is a phenomenon that can be found in ASD
      subjects during gait, even if this condition was found not to be necessarily
      related only to walking, since these children often also stand and run on their
      tiptoes. Since persistent TW in ASD subjects may contribute to secondary
      shortening of the Achilles's tendon, it becomes important to have an assessment
      tool and/or outcome measure for both the clinical and rehabilitative settings.
      The aim of this systematic review is to critically evaluate and describe the
      methods employed to assess toe walking in ASD subjects. The systematic review
      protocol was previously registered on PROSPERO. We conducted an extensive
      literature search in PubMed, CINAHL, PsycINFO, The Cochrane Library, and Scopus
      databases. There were no restrictions on the types of study design eligible for
      inclusion. Ten studies were included in the systematic review. Risk of bias of
      the included studies was conducted using the following instruments depending on
      the study types: STROBE Statement, Cochrane risk of bias tool, and CARE
      checklist. Almost all the included studies (8/10) proposed a tip-toe behavior
      (TTB) assessment only during walking. Nine out of ten of the included studies
      assessed TTB using a qualitative methodology. The results evidenced the
      heterogeneity of qualitative methods and a lack of a structured quantitative test
      to assess toe walking in ASD subjects. Autism Res 2018, 11: 1404-1415. (c) 2018
      International Society for Autism Research, Wiley Periodicals, Inc. LAY ABSTRACT:
      Toe walking (TW) is a phenomenon that can be found during ASD subject's gait. The
      persistence of this behavior may contribute to secondary Achilles's tendon
      shortening. In this perspective it becomes important to have an assessment tool
      and/or outcome measure for both the clinical and rehabilitative settings. The
      current systematic review aimed to describe the methods employed to assess TW.
      The results evidenced the lack and the need of a structured quantitative test to
      assess TW in ASD subjects.

PMID- 30199609
TI  - Evaluation of dehydrated human umbilical cord biological properties for wound
      care and soft tissue healing.
AB  - Chronic wounds are a significant health care problem with serious implications
      for quality of life because they do not properly heal and often require
      therapeutic intervention. Amniotic membrane allografts have been successfully
      used as a biologic therapy to promote soft tissue healing; however, the umbilical
      cord, another placental-derived tissue, has also recently garnered interest
      because of its unique composition but similar placental tissue origin. The aim of
      this study was to characterize PURION(r) PLUS Processed dehydrated human
      umbilical cord (dHUC) and evaluate the biological properties of this tissue that
      contribute to healing. This was performed through the characterization of the
      tissue composition, evaluation of in vitro cellular response to dHUC treatment,
      and in vivo bioresorption and tissue response in a rat model. It was observed
      that dHUC contains collagen I, hyaluronic acid, laminin, and fibronectin.
      Additionally, 461 proteins that consist of growth factors and cytokines,
      inflammatory modulators, chemokines, proteases and inhibitors, adhesion
      molecules, signaling receptors, membrane-bound proteins, and other soluble
      regulators were detected. Cell-based assays demonstrated an increase in adipose
      derived stem cell and mesenchymal stem cell proliferation, fibroblast migration
      and endothelial progenitor cell vessel formation in a dose-dependent manner after
      dHUC treatment. Lastly, rat subcutaneous implantation demonstrated
      biocompatibility since dHUC allografts were resorbed without fibrous
      encapsulation. These findings establish that dHUC possesses biological properties
      that stimulate cellular responses important for soft tissue healing. (c) 2018 The
      Authors. Journal Of Biomedical Materials Research Part B: Applied Biomaterials
      Published By Wiley Periodicals, Inc. J Biomed Mater Res B Part B: Appl Biomater,
      2018.

PMID- 30199610
TI  - Synthesis and Morphology Evolution of Ultrahigh Content Nitrogen-Doped, Micropore
      Dominated Carbon Materials as High-Performance Supercapacitors.
AB  - Nitrogen-doped carbon-based materials including nanocarbons, graphene, and
      conductive polymers are impressive as supercapacitor electrodes. However,
      ultrahigh nitrogen contents, micropore dominated, and morphology evolving
      carbonaceous electrodes have not achieved until now which are crucial for
      supercapacitor. Herein, we prepare a novel fumaronitrile (FUM) derived covalent
      triazine framework (FUM-CTF) and activated it by using KOH at different
      temperatures to obtain the corresponding carbon materials, which were used as
      supercapacitor electrode materials. Specially, the FUM-700 (sample activated at
      700  degrees C) possesses an excellent specific capacitance of 400 F g-1 at a
      current density of 1 A g-1 and considerable energy density over 18 Wh kg-1 in KOH
      (6 m) aqueous electrolyte. In addition, this electrode shows 260 F g-1 at a
      current density of 20 A g-1 for charge/discharge operation. Furthermore, the FUM
      700 electrode demonstrates extraordinary electrochemical stability with 97 %
      retention after 10 000 cycles at 10 A g-1 . Ultrahigh nitrogen contents, the
      microporous structure, and the inner nanoparticle morphology work in concert to
      contribute to the superior electrochemical performance of FUM-700. Our work might
      give some hints to help design other high-performance nitrogen-containing
      supercapacitor electrode materials.

PMID- 30199611
TI  - Anti-Flt1 peptide and cyanine-conjugated gold nanoparticles for the concurrent
      antiangiogenic and endothelial cell proton treatment.
AB  - Anti-Flt1 peptide of GNQWFI binds to vascular endothelial growth factor receptor
      1 (VEGFR1 or Flt1) and prevents binding of VEGF, inhibiting VEGFR1-mediated
      endothelial cell migration and tube formation. Bare gold nanoparticle (AuNP) was
      known to have anti-angiogenic properties by specific binding with VEGF. In this
      study, anti-Flt1 peptide (GGNQWFI) and cyanine were chemically conjugated to
      AuNPs (Flt1@AuNP-cyanine 5.5 or Flt1@AuNP-hydrocyanine 5.5 [HCy5.5]) to enhance
      antiangiogenic properties with targeting to VEGFR-1 as well as producing Coulomb
      nanoradiator therapeutic effect on the retinal endothelial cells. Anti-Flt1 AuNP
      complex showed binding with VEGFR-1 and showed more protein-induced fluorescence
      enhancement (PIFE) by various VEGFs compared with bare AuNPs, suggesting enhanced
      antiangiogenic properties compared to bare AuNP. Nonfluorescent Flt1@AuNP-HCy5.5
      successfully reacted with reactive oxygen species (ROS) produced from Fenton
      reactions or a proton-induced Coulomb nanoradiator, enabling quenching-free
      oxidant fluorescence ROS imaging in HRMECs under oxidative stress. Flt1@AuNP
      HCy5.5 alone induced 50% greater cytotoxicity for HRMECs compared to bare AuNPs
      and 80% greater cell death by the Au-nanoradiator effect. In conclusion, this
      study describes a new therapeutic anti-Flt1 gold nanocomplex with enhanced
      antiangiogenic properties and nanoradiator-mediated cytotoxicity on retinal
      endothelial cells. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res B Part B,
      2018.

PMID- 30199613
TI  - [Construction of A Genetic Linkage Map in Salvia miltiorrhiza].
AB  - Objective: On the basis of previous studies, to construct a genetic map of Salvia
      miltiorrhiza by using EST-SSR primers, to build a platform for positioning
      important traits relating to genes, the cloning and molecular marker-assisted in
      breeding of new varieties of Salvia miltiorrhiza. Methods: A total of 411 EST-SSR
      primers were used for PCR amplification to screen polymorphic markers in F1
      mapping population derived from a cross between Salvia miltiorrhiza, two parents
      of which were the cultivars of ZH74 and BH18. Combined with the molecular marker
      data of previous studies, Joinmap 4. 0 software was used for map integration.
      Results: 411EST-SSR primers were screened from two parents, a total of 328 pairs
      of primers were amplified stable products,164 pairs of polymorphic primers were
      obtained. Conclusion: A linkage map of Salvia miltiorrhiza with 150 marker high
      density genetic is constructed.

PMID- 30199612
TI  - Not all pycnodysostosis-related mutants of human cathepsin K are inactive -
      crystal structure and biochemical studies of an active mutant I249T.
AB  - Human cathepsin K (CTSK) is a collagenolytic lysosomal cysteine protease that
      plays an important role in bone turnover. Mutation in CTSK gene is associated
      with loss of collagenolytic activity of CTSK leading to an autosomal recessive
      bone disorder called pycnodysostosis. Although a number of pycnodysostotic
      missense mutations have been reported, underlying mechanism of the disease is not
      clear. In this study, we investigated in vitro six recombinant pycnodysostosis
      related mutants of human CTSK (G79E, I249T, G243E, G303E, G319C and Q187P). While
      all the mutants, like wild-type, show similar high levels of expression in
      Escherichia coli, four of them (G79E, G303E, G319C and Q187P) are inactive,
      unstable and spontaneously degrade during purification process. In contrast,
      proteolytic/collagenolytic activity, zymogen activation kinetics and stability of
      G243E and I249T mutants are nominally affected. Crystal structure of I249T at
      1.92 A resolution shows that the mutation in R-domain causes conformational
      changes of a surface loop in the L-domain although the catalytic cleft remains
      unaltered. Molecular simulation, normal mode analysis and fluorescence lifetime
      measurement eliminated the possibility that the change in L-domain surface loop
      orientation is a crystallization artefact. CD-based thermal melting profile
      indicates that stability of I249T is significantly higher than wild-type. Our
      studies first time reports that pycnodysostosis-related mutations do not always
      lead to complete loss of general proteolytic activity or specific collagenolytic
      activity of CTSK. The first crystal structure of a pycnodysostotic mutant (I249T)
      provides critical information that may pave new avenues towards understanding the
      disease at molecular level. DATABASE: The atomic co-ordinates and structure
      factors for I249T mutant of human CTSK (codes 5Z5O) have been deposited in the
      Protein Data Bank (http://wwpdb.org/).

PMID- 30199614
TI  - [Rapid Propagation in vitro of Dioscorea opposita 'Guangfeng'and Its Stomatal
      Observation,FCM Analysis of Chromosome Ploidy and ISSR Detection of DNA
      Mutation].
AB  - Objective: To study the rapid propagation in vitro of Dioscorea
      opposita'Guangfeng', and to observe the stomas of the transplanting plantlets and
      potted seedlings, to test chromosome ploidy by FCM, and to detect DNA mutation by
      ISSR,in order to provide the technical basis for the large-scale production of
      Dioscorea opposita 'Guangfeng' plantlets. Methods: The technique system of
      Dioscorea opposita 'Guangfeng'rapid propagation in vitro was established and
      optimized by plant tissue culture method. The parameters of transplanting
      plantlets and potted seedlings were studied as follows, the stomatal parameters
      were observed by transparent adhesive tape method, chromosome ploidy were
      analyzed by FCM, and DNA mutation were detected by ISSR molecular marker.
      Results: The technique system of Dioscorea opposite 'Guangfeng' rapid propagation
      in vitro was as follows, slightly woody stem segment with a bud were selected and
      inoculated onto MS + KT 1 mg / L + NAA 0. 2 mg / L solid culture medium and
      cultured in the photoperiod of 14 h / d( the temperature was( 25 +/- 2) C and
      light intensity was 1 500 ~ 2 000 Lx) after disinfected for 1 min in 70% alcohol
      prior to sterilized for 12 min with 0. 1% Hg Cl2,the materials were washed with
      sterile water for 3 times, respectively. The new bud was cut off when it grew to
      2 ~ 3cm and inoculated into MS + KT 2 mg / L + NAA 0. 5 mg / L liquid culture
      medium and continued to culture in above culture conditions. The whole plant was
      formed after cultured for about 90 d. The sealing membrane was opened in
      transplanting, and the plantlets was still placed in above culture conditions and
      cultured for 2 ~ 3 d, and then the whole plant was taken out, and the culture
      medium washed off and then transferred into the vessel with shallow liquid MS
      basic culture medium and domesticated indoor. The acclimated plantlets were taken
      out and transplanted in the outdoor pots with the sandy soil when the new shoots
      grew out, and watered one time with tap water in the morning and evening per day,
      the survival rate reached 100%. The results of stomatal observation, FCM analysis
      and ISSR detection of transplanting plantlets and potted seedlings showed that
      the stomatal parameters, chromosome ploidy and DNA mutation of plantlets and
      potted seedlings had no variation. Conclusion: The results reveal that the
      establishment and optimization of the technique system of Dioscorea opposita
      'Guangfeng' rapid propagation in vitro is feasible, and the regenerated plants do
      not have genetic variation which can ensure the stability of the genetic.

PMID- 30199615
TI  - [Research on Breeding of the New Rehmannia glutinosa Variety].
AB  - Objective: To breed new Rehmannia glutinosa varieties with best comprehensive
      properties. Methods: By space mutation of hybrid seeds of 85-5 and Beijing No.
      1,after systemic breeding, Huaidi 81 with excellent comprehensive characters was
      screened. Fresh weight, benchmark composition content, resistance, chlorophyll
      and anthocyanin content, photosynthetic characteristics of the new variety and
      the main cultivars were determined. Results: Per plant fresh weight of Huaidi 81
      was higher than those five main varieties and there was extremely significant
      difference between Huaidi 81 and other varieties,the yield of Huaidi 81( 82 353
      kg / hm2) was29. 7% higher than that 5 main varieties. The catalpol content of
      different Rehmannia glutinosa varieties ranked in the order as follows, Beijing
      No. 3( 1. 601%) > Qinhuai( 1. 588%) > Huaidi 81( 1. 314%) > Godden nine > 85-5(
      1. 073%) > Huaifeng( 0. 924%),the catalpol content of Huaidi 81 was in the
      middle, and there was no significant difference between Huaidi 81 and Godden
      nine,but extremely significant difference from other varieties. The acteoside
      content of different Rehmannia glutinosa varieties ranked in the order as
      follows,Huaidi 81( 0. 096%) > Qin Huai( 0. 069%) > 85-5( 0. 047%) > Beijing No.
      3( 0. 035%) > Huaifeng( 0. 023%) > Golden nine( 0. 022%),the content of acteoside
      of Huaidi 81 was higher than those five main varieties, and there was extremely
      significant difference between Huaidi 81 and other varieties. Huaidi 81 had high
      resistance to Septoris digitalis, and had middle resistance to leaf ring rot,
      which indicated that Huaidi 81 had good resistance to leaf disease. Huaidi 81
      with the highest chlorophyll content and moderate anthocyanin content, and had
      the highest photosynthetic rate. Conclusion: The new variety Huaidi 81 with best
      comprehensive properties is suitable for popularizing as a new Rehmannia
      glutinosa variety.

PMID- 30199616
TI  - Intracellular DNA Cargo Release from a Gold Nanoparticle Modulated by the Nature
      of the Surface Coupling Functionality.
AB  - Covalently coupling nucleic acids to a gold nanoparticle (AuNP) surface has been
      demonstrated for generating effective gene therapy agents to modify cellular
      protein expression. The therapeutic efficacy of the approach is anticipated to be
      impacted by the length of time the nucleic acid sequence resides in the
      endolysosomal pathway once transfected into a cell. It is believed that the
      dynamics of the processing should reflect the linkage chemistry of the DNA to the
      AuNP surface. In this manuscript the dynamics of nanotherapeutic uptake, nucleic
      acid release, and gene processing are investigated  in vitro for a AuNP-nucleic
      acid delivery platform transfected into A375 human melanoma cells, as a function
      of the nucleic acid-gold linkage chemistry. The dynamics of cell processing of
      the single monodentate thiol (SX), bidentate dual thiol (SS), or mixed bidentate
      thiol plus amine (SN) coordination of nucleic acids to the AuNP surface are
      evaluated using a multicolor nanosurface energy transfer bio-optical transponder
      (SET-BOT) technology. The use of live-cell fluorescence microscopy allows for the
      direct visualization of the uptake and localization of a lipofectamine-packaged
      SET-BOT using a dye (DL700) that is not quenched in the proximity of the AuNP,
      while fluorescence "turn on" of a dye that is proximally quenched by the AuNP
      (DL488) is used to report on the dynamics of release of the nucleic acid cargo
      within the cell. For protein expression following transcription of the gene, the
      emission signature of a red fluorescent protein, tdTomato, is monitored. The
      intracellular rates of DNA release from the AuNP surface once endosomally
      packaged within the A375 human melanoma cells were found to follow the binding
      activity series: bidentate thiol > bidentate thiol plus amine > monodentate
      thiol, consistent with the strength of multidentate chelation, paired with the
      stabilizing influence of pi-backbonding of thiols compared to sigma-donation in
      amines, when bound to a gold surface.

PMID- 30199617
TI  - Development of a Multiplexed Activity-Based Protein Profiling Assay to Evaluate
      Activity of Endocannabinoid Hydrolase Inhibitors.
AB  - Endocannabinoids, an important class of signaling lipids involved in health and
      disease, are predominantly synthesized and metabolized by enzymes of the serine
      hydrolase superfamily. Activity-based protein profiling (ABPP) using fluorescent
      probes, such as fluorophosphonate (FP)-TAMRA and beta-lactone-based MB064,
      enables drug discovery activities for serine hydrolases. FP-TAMRA and MB064 have
      distinct, albeit partially overlapping, target profiles but cannot be used in
      conjunction due to overlapping excitation/emission spectra. We therefore
      synthesized a novel FP-probe with a green BODIPY as a fluorescent tag and studied
      its labeling profile in mouse proteomes. Surprisingly, we found that the reporter
      tag plays an important role in the binding potency and selectivity of the probe.
      A multiplexed ABPP assay was developed in which a probe cocktail of FP-BODIPY and
      MB064 visualized most endocannabinoid serine hydrolases in mouse brain proteomes
      in a single experiment. The multiplexed ABPP assay was employed to profile
      endocannabinoid hydrolase inhibitor activity and selectivity in the mouse brain.

PMID- 30199618
TI  - Selective SnO x Atomic Layer Deposition Driven by Oxygen Reactants.
AB  - SnO x thin films were successfully deposited by the thermal atomic layer
      deposition (ALD) method using N, N'- tert-butyl-1,1-dimethylethylenediamine
      stannylene(II) as a precursor and ozone and water as reactants. The growth of SnO
      and SnO2 films could be easily controlled by employing different reactants and
      utilizing different ozone and water concentrations, respectively. The formation
      of both SnO and SnO2 films exhibited typical surface-limiting reaction
      characteristics, although their growth behaviors differ from one another. The
      combined studies of density functional theory calculations and experimental
      analyses showed that the difference in growth behavior of the SnO and SnO2 films
      can be attributed to the stability of ozone and water on the SnO2 and SnO films.
      SnO and SnO2 films have different crystal structures and both films were
      crystallized from the amorphous to polycrystalline states following an increase
      in the deposition temperature. The absorbance and refractive index of the thin
      films were investigated using ultraviolet-visible spectroscopy (UV-vis) and
      spectroscopic ellipsometry (SE), respectively. SnO x films formed using ozone and
      water as a reactant showed an optical band gap of 3.60-3.17 eV and 2.24-2.30 eV
      and refractive indices of ~2.0 and ~2.6, respectively, which correspond to values
      typical of SnO2 and SnO. The bilayer structure of SnO/SnO2 was successfully
      fabricated on indium tin oxide (ITO) glass with nickel as a top electrode at 100 
      degrees C. The SnO/SnO2 bilayer exhibited diode characteristics with a current
      rectification ratio of 15. Our results present a simple but highly versatile
      growth method for producing multilayer oxide films with electronic properties
      that can be finely controlled.

PMID- 30199619
TI  - Detection of Inosine on Transfer RNAs without a Reverse Transcription Reaction.
AB  - Inosine at the "wobble" position (I34) is one of the few essential
      posttranscriptional modifications in tRNAs (tRNAs). It results from the
      deamination of adenosine and occurs in bacteria on tRNAArgACG and in eukarya on
      six or seven additional tRNA substrates. Because inosine is structurally a
      guanosine analogue, reverse transcriptases recognize it as a guanosine. Most
      methods used to examine the presence of inosine rely on this phenomenon and
      detect the modified base as a change in the DNA sequence that results from the
      reverse transcription reaction. These methods, however, cannot always be applied
      to tRNAs because reverse transcription can be compromised by the presence of
      other posttranscriptional modifications. Here we present SL-ID (splinted ligation
      based inosine detection), a reverse transcription-free method for detecting
      inosine based on an I34-dependent specific cleavage of tRNAs by endonuclease V,
      followed by a splinted ligation and polyacrylamide gel electrophoresis analysis.
      We show that the method can detect I34 on different tRNA substrates and can be
      applied to total RNA derived from different species, cell types, and tissues.
      Here we apply the method to solve previous controversies regarding the
      modification status of mammalian tRNAArgACG.

PMID- 30199620
TI  - The Osmolyte TMAO Modulates Protein Folding Cooperativity by Altering Global
      Protein Stability.
AB  - The folding of many globular proteins from the unfolded (U) to the native (N)
      state appears to be describable by a two-state N <-> U model, which has led to
      the general belief that protein folding occurs in a highly cooperative manner.
      One reason for the widespread belief in "two-state folding" is that protein
      folding reactions are invariably studied by ensemble averaging probes and not by
      probes that can distinguish as well as quantify the multiple conformations that
      may be present. Consequently, how cooperativity is affected by protein stability,
      protein sequence, and solvent conditions is poorly understood. In this study,
      hydrogen exchange coupled to mass spectrometry (HX-MS) of the PI3K SH3 domain was
      carried out in the presence of a stabilizing osmolyte, trimethylamine N-oxide
      (TMAO). By showing that HX occurs under the EX1 regime even in the presence of 2
      M TMAO, we were able to examine the temporal evolution of the populations of the
      different conformations present together. A strong link between protein folding
      cooperativity and protein stability is revealed. Increasing stability is
      accompanied by an increase in the ruggedness of the free energy landscape as well
      as diminished cooperativity; the number of amide sites simultaneously opening up
      their structure decreases with an increase in TMAO concentration. A comparison of
      the effect of TMAO to that of urea on the intrinsic dynamics of the PI3K SH3
      domain indicates that TMAO counteracts the effect of urea not only on protein
      stability but also on protein folding cooperativity.

PMID- 30199621
TI  - Graphene Oxide Based Recyclable in Vivo Device for Amperometric Monitoring of
      Interferon-gamma in Inflammatory Mice.
AB  - Cytokine sensing is challenging due to their typically low abundances in
      physiological conditions. Nanomaterial fabricated interfaces demonstrated unique
      advantages in ultrasensitive sensing. Here, we demonstrate an amperometric
      sensing device based on graphene oxide (GO) and structure-switching aptamers for
      long-term detection of cytokines in a living organism. The device incorporates a
      single layer of GO acting as a signal amplifier on glassy carbon electrodes. The
      hairpin aptamers specific to interferon-gamma (IFN-gamma), which were loaded with
      redox probes, are covalently attached to GO to serve as biorecognition moieties.
      IFN-gamma was able to trigger the configuration change of aptamers while
      releasing the trapped redox probes to introduce the electrochemical signal. This
      in vivo device was capable of quantitatively and dynamically detecting IFN-gamma
      down to 1.3 pg mL-1 secreted by immune cells in cell culture medium with no
      baseline drift even at a high concentration of other nonspecific proteins. The
      biocompatible devices were also implanted into subcutaneous tissue of enteritis
      mice, where they performed precise detection of IFN-gamma over 48 h without using
      physical barriers or active drift correction algorithms. Moreover, the device
      could be reused even after multiple rounds of regeneration of the sensing
      interface.

PMID- 30199622
TI  - Ionic Conductivity in Ionic Liquid Nano Thin Films.
AB  - Thin film approaches are powerful methods for gaining a nanoscale understanding
      of interfacial ionic liquids (ILs) in the vicinity of solids. These approaches
      are used to directly elucidate the interfacial contributions to the physical
      properties of ILs as nanoscale thin films have significant proportions of the
      surface or interface region with respect to their total volume. Here, we report
      the growth of a uniform [emim][TFSA] thin film ionic liquid on a chemically
      modified, well-wettable sapphire, thereby allowing the in situ measurement of its
      ionic conductivity on the nanoscale. We observed the thickness-dependent behavior
      of the ionic conductivity, which gradually decreased especially when the
      thickness was less than 10 nm, and found it to be quantitatively analyzed well by
      using an empirical two-layer model. The molecular dynamics (MD) simulations show
      that the thickness-dependent ionic conductivity originates from the solid-like
      structuring of the IL near the substrate, reproducing a thickness-dependent ionic
      conductivity. The MD simulation results suggest that the thickness of the low
      conductivity region determined in the two-layer model should roughly correspond
      to the thickness of the solid-like structuring of the IL near the substrate.

PMID- 30199623
TI  - Particle Packing Theory Guided Thermal Conductive Polymer Preparation and Related
      Properties.
AB  - Thermal conductive polymer composites are satisfying for thermal management of
      electronic devices. However, how to choose the sizes of thermal conductive
      fillers to get a high thermal conductivity of composites are still clueless and
      poor filler size matching will also affect the processability of the composites.
      Closest packing model was used to guide multiscale thermal conductive particles
      filling silicone rubber in this work. A highest thermal conductivity of 1.381 W.m
      1.K-1 at filler loading of 50 vol % was determined among nine comparing
      formulations. The fillers with small particle size filled the interspaces of
      fillers with large particle size to form more complete thermal conduction paths
      and heat dissipation was increased. The apparent densities and rheological tests
      further verified the effectiveness of closest packing model. This study provides
      theoretical guidance for thermal conductive polymer composites to achieve high
      thermal conductivity and good processability, which has an important practical
      application.

PMID- 30199624
TI  - Tunable Buckled Beams with Mesoporous PVDF-TrFE/SWCNT Composite Film for Energy
      Harvesting.
AB  - By incorporating mesoporous piezoelectric materials and tuning mechanical
      boundary conditions a simple beam structure can significantly take advantage of
      limited mechanical displacements for energy harvesting. Specifically, we employed
      a mesoporous PVDF-TrFE composite thin film mixed with single-wall carbon
      nanotubes to improve the formation of the crystalline phase in this piezoelectric
      polymer. The film was then patterned on a thin buckled beam to form a compact
      energy harvester, which was used to study the effects of two boundary conditions,
      including the end rotation angle and the location of a mechanical stop along the
      beam. We carefully designed controlled experiments using mesoporous PVDF-TrFE
      film and PVDF-TrFE/SWCNT composite films, both of which were tested under two
      cases of boundary conditions, namely, the rotation of the end angle and the
      addition of a mechanical stop. The voltage and current of the energy harvester
      under these two boundary conditions were, respectively, increased by
      approximately 160.1% and 200.5% compared to the results of its counterpart
      without imposing any boundary conditions. Thereby, our study offers a promising
      platform for efficiently powering implantable and wearable devices for harnessing
      energy from the human body which would otherwise have been wasted.

PMID- 30199625
TI  - Ultrathin Gold Nanowires with the Polytetrahedral Structure of Bulk Manganese.
AB  - Despite the intensive interest in thin gold nanowires for a variety of
      technologically important applications, key details of the mechanism of their
      formation and atomic-scale structure remain unknown. Here we synthesize highly
      uniform, very long, and ultrathin gold nanowires in a liquid-phase environment
      and study their nucleation and growth using in situ high-energy synchrotron X-ray
      diffraction. By controlling the type of solvents, reducing agents, and gold
      precursor concentration, it is shown that the nucleation and growth of gold
      nanowires involve the emergence and self-assembly of transient linear gold
      complexes, respectively. In sharp contrast with the face-centered-cubic bulk
      gold, the evolved nanowires are found to possess a tetrahedrally close packed
      structure incorporating distorted icosahedra and larger size coordination
      polyhedra of the type observed with the room-temperature phase of bulk manganese.
      We relate the complexes to synergistic effects between the selected precursor and
      reducing agents that become appreciable over a narrow range of their molar
      ratios. We attribute the unusual structural state of gold nanowires to
      geometrical frustration effects arising from the conflicting tendencies of
      assemblies of metal atoms to evolve toward attaining high atomic packing density
      while keeping the atomic-level stresses low, ultimately favoring the growth of
      cylindrical nanowires with a well-defined diameter and atomically smooth surface.
      Our work provides a roadmap for comprehensive characterization and, hence, better
      understanding of 1D metallic nanostructures with an unusual atomic arrangement
      and may have important implications for their synthesis and performance in
      practical applications.

PMID- 30199626
TI  - Highly Sensitive, Visible Blind, Wearable, and Omnidirectional Near-Infrared
      Photodetectors.
AB  - Visible blind near-infrared (NIR) photodetection is essential when it comes to
      weapons used by military personnel, narrow band detectors used in space
      navigation systems, medicine, and research studies. The technological field of
      filterless visible blind, NIR omnidirectional photodetection and wearability is
      at a preliminary stage. Here, we present a filterless and lightweight design for
      a visible blind and wearable NIR photodetector capable of harvesting light
      omnidirectionally. The filterless NIR photodetector comprises the integration of
      distinct features of lanthanide-doped upconversion nanoparticles (UCNPs),
      graphene, and micropyramidal poly(dimethylsiloxane) (PDMS) film. The lanthanide
      doped UCNPs are designed such that the maximum narrow band detection of NIR is
      easily accomplished by the photodetector even in the presence of visible light
      sources. Especially, the 4f n electronic configuration of lanthanide dopant ions
      provides for a multilevel hierarchical energy system that provides for longer
      lifetime of the excited states for photogenerated charge carriers to transfer to
      the graphene layer. The graphene layer can serve as an outstanding conduction
      path for photogenerated charge carrier transfer from UCNPs, and the flexible
      micropyramidal PDMS substrate provides an excellent platform for omnidirectional
      NIR light detection. Owing to these advantages, a photoresponsivity of ~800 AW-1
      is achieved by the NIR photodetector, which is higher than the values ever
      reported by UCNPs-based photodetectors. In addition, the photodetector is
      stretchable, durable, and transparent, making it suitable for next-generation
      wearable optoelectronic devices.

PMID- 30199627
TI  - Design of Modular Polyhydroxyalkanoate Scaffolds for Protein Immobilization by
      Directed Ligation.
AB  - In vivo-assembled polyhydroxyalkanoate (PHA) particles have been successfully
      bioengineered to display foreign protein functions toward high-value applications
      in medicine and industry. To further expand the design space of PHA particles
      toward immobilization of various functional proteins, we developed a tunable
      modular protein immobilization method implementing the SpyCatcher/SpyTag
      chemistry. We successfully displayed the SpyCatcher protein using translational
      fusion with the Ralstonia eutropha PHA synthase (PhaC). The SpyCatcher domain
      displayed on the surface of PHA particles was accessible for cross-linker-free
      ligation with SpyTag-bearing proteins. We demonstrated tunable protein
      immobilization of various SpyTagged proteins on SpyCatcher-PHA particles, which
      ultimately enabled assembly of multiple proteins coating the surface of PHA
      particles. Overall, the functionality, stability, and reusability of proteins
      immobilized to SpyCatcher-PHA particles were either retained or enhanced in
      comparison to the soluble forms. This modular platform can be implemented as a
      generic tool for protein immobilization in an array of applications.

PMID- 30199628
TI  - A Facile and Scalable Route to the Preparation of Catalytic Membranes with in
      Situ Synthesized Supramolecular Dendrimer Particle Hosts for Pt(0) Nanoparticles
      Using a Low-Generation PAMAM Dendrimer (G1-NH2) as Precursor.
AB  - Since the first reports of Cu dendrimer-encapsulated nanoparticles (DENs)
      published in 1998, the dendrimer-templating method has become the best and most
      versatile method for preparing ultrafine metallic and bimetallic nanoparticles (1
      3 nm) with well-defined compositions, high catalytic activity, and tunable
      selectivity. However, DENs have remained for the most part model systems with
      limited prospects for scale up and integration into high-performance and reusable
      catalytic modules and systems for industrial-scale applications. Here, we
      describe a facile and scalable route to the preparation of catalytic
      polyvinylidene fluoride (PVDF) membranes with in situ synthesized supramolecular
      dendrimer particles (SDPs) that can serve as hosts and containers for Pt(0)
      nanoparticles (2-3 nm). These new catalytic membranes were prepared using a
      reactive encapsulation process similar to that utilized to prepare Pt DENs by
      addition of a reducing agent (sodium borohydride) to aqueous complexes of Pt(II)
      + G4-OH/G6-OH polyamidoamine (PAMAM) dendrimers. However, the SDPs (2.4 MUm
      average diameter) of our new mixed matrix PVDF-PAMAM membranes were synthesized
      in the dope dispersion without purification prior to film casting using (i) a low
      generation PAMAM dendrimer (G1-NH2) as particle precursor and (ii)
      epichlorohydrin, an inexpensive functional reagent, as cross-linker. In addition,
      the membrane PAMAM particles contain secondary amine groups (~1.9 mequiv per gram
      of dry membrane), which are more basic and thus have higher Pt binding affinity
      than the tertiary amine groups of the G4-OH and G6-OH PAMAM dendrimers. Proof-of
      concept experiments show that our new PVDF-PAMAM-G1-Pt/membranes can serve as
      highly active and reusable catalysts for the hydrogenation of alkenes and alkynes
      to the corresponding alkanes using (i) H2 at room temperature and a pressure of 1
      bar and (ii) low catalyst loadings of ~1.4-1.6 mg of Pt. Using cyclohexene as
      model substrate, we observed near quantitative conversion to cyclohexane (~98%).
      The regeneration studies showed that our new Pt/membrane catalysts are stable and
      can be reused for five consecutive reaction cycles for a total duration of 120 h
      including 60 h of heating at 100  degrees C under vacuum for substrate, product,
      and solvent removal with no detectable loss of cyclohexene hydrogenation
      activity. The overall results of our study point to a promising, versatile, and
      scalable path for the integration of catalytic membranes with in situ synthesized
      SDP hosts for Pt(0) nanoparticles into high-throughput modules and systems for
      heterogeneous catalytic hydrogenations, an important class of reactions that are
      widely utilized in industry to produce pharmaceuticals, agrochemicals, and
      specialty chemicals.

PMID- 30199629
TI  - Genome-Centered Metagenomics Analysis Reveals the Symbiotic Organisms Possessing
      Ability to Cross-Feed with Anammox Bacteria in Anammox Consortia.
AB  - Although using anammox communities for efficient wastewater treatment has
      attracted much attention, the pure anammox bacteria are difficult to obtain, and
      the potential roles of symbiotic bacteria in anammox performance are still
      elusive. Here, we combined long-term reactor operation, genome-centered
      metagenomics, community functional structure, and metabolic pathway
      reconstruction to reveal multiple potential cross-feedings during anammox reactor
      start-up according to the 37 recovered metagenome-assembled genomes (MAGs). We
      found Armatimonadetes and Proteobacteria could contribute the secondary
      metabolites molybdopterin cofactor and folate for anammox bacteria to benefit
      their activity and growth. Chloroflexi-affiliated bacteria encoded the function
      of biosynthesizing exopolysaccharides for anammox consortium aggregation, based
      on the partial nucleotide sugars produced by anammox bacteria. Chlorobi
      affiliated bacteria had the ability to degrade extracellular proteins produced by
      anammox bacteria to amino acids to affect consortium aggregation. Additionally,
      the Chloroflexi-affiliated bacteria harbored genes for a nitrite loop and could
      have a dual role in anammox performance during reactor start-up. Cross-feeding in
      anammox community adds a different dimension for understanding microbial
      interactions and emphasizes the importance of symbiotic bacteria in the anammox
      process for wastewater treatment.

PMID- 30199630
TI  - Linking N2O Emissions from Biofertilizer-Amended Soil of Tea Plantations to the
      Abundance and Structure of N2O-Reducing Microbial Communities.
AB  - Nitrous oxide (N2O) contributes up to 8% of global greenhouse gas emissions, with
      approximately 70% from terrestrial sources; over one-third of this terrestrial
      emission has been linked to increased agricultural fertilizer use. Much of the
      nitrogen in fertilizers is converted to N2O by microbial processes in soil.
      However, the potential mechanism of biofertilizers and the role of microbial
      communities in mitigating soil N2O emissions are not fully understood. Here, we
      used a greenhouse-based pot experiment with tea plantation soil to investigate
      the effect of Trichoderma viride biofertilizer on N2O emission. The addition of
      biofertilizer reduced N2O emissions from fertilized soil by 67.6%. Quantitative
      PCR (qPCR) analysis of key functional genes involved in N2O generation and
      reduction ( amoA, nirK, nirS, and nosZ) showed an increased abundance of nirS and
      nosZ genes linked to the pronounced reduction in N2O emissions. High-throughput
      sequencing of nosZ showed enhanced relative abundance of nosZ-harboring
      denitrifiers in the T. viride biofertilizer treatments, thus linking greater N2O
      reduction capacity to the reduced emissions. Our findings showed that
      biofertilizers can affect the microbial nitrogen transformation process and
      reduce N2O emissions from agroecosystems.

PMID- 30199631
TI  - New Crystallographic Snapshots of Large Domain Movements in Bacterial 3-Hydroxy-3
      methylglutaryl Coenzyme A Reductase.
AB  - The enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (HMGR)
      catalyzes the first committed step of the mevalonate pathway, which is used
      across biology in the biosynthesis of countless metabolites. HMGR consumes 2
      equiv of the cofactor NAD(P)H to perform the four-electron reduction of HMG-CoA
      to mevalonate toward the production of steroids and isoprenoids, the largest
      class of natural products. Recent structural data have shown that HMGR contains a
      highly mobile C-terminal domain (CTD) that is believed to adopt many different
      conformations to permit binding and dissociation of the substrate, cofactors, and
      products at specific points during the reaction cycle. Here, we have
      characterized the HMGR from Delftia acidovorans as an NADH-specific enzyme and
      determined crystal structures of the enzyme in unbound, mevalonate-bound, and
      NADH- and citrate-bound states. Together, these structures depict ligand binding
      in both the active site and the cofactor-binding site while illustrating how a
      conserved helical motif confers NAD(P)H cofactor specificity. Unexpectedly, the
      NADH-bound structure also reveals a new conformation of the CTD, in which the
      domain has "flipped" upside-down, while directly binding the cofactor. By
      capturing these structural snapshots, this work not only expands the known range
      of HMGR domain movement but also provides valuable insight into the catalytic
      mechanism of this biologically important enzyme.

PMID- 30199632
TI  - A Simple Correction for Nonadditive Dispersion within Extended Symmetry-Adapted
      Perturbation Theory (XSAPT).
AB  - Extended symmetry-adapted perturbation theory (XSAPT), in conjunction with
      empirical "+ aiD" potentials fit to ab initio dispersion data, is a low-scaling
      approach to compute intermolecular interaction energies in noncovalent clusters.
      One shortcoming is that the aiD atom-atom dispersion potentials are independent
      of the chemical environment of the atoms in question and therefore neglect
      nonadditive dispersion effects. These can be significant in large systems, so to
      account for them we test a simple correction to XSAPT(KS)+ aiD, where "KS"
      indicates the use of Kohn-Sham orbitals. This correction, which can be evaluated
      at fourth-order cost using double-zeta basis sets, is based on comparing second
      order SAPT dispersion with and without a self-consistent charge embedding for the
      monomer wave functions. The correction amounts to ~1.4 kcal/mol in (H2O)6 but
      ~5.5 kcal/mol in (H2O)20. With the nonadditive dispersion correction, XSAPT(KS)+
      aiD affords errors of ~1 kcal/mol for isomers of F-(H2O)10 and (H2O)20, where the
      benchmarks are complete-basis CCSD(T) energies, as well as for ion-water clusters
      X(H2O) n where n <= 6 and X = F-, Cl-, SO42-, Li+, Na+, or K+. We also test the
      MP2 method and a variety of density-functional methods that have been
      specifically recommended for noncovalent interactions. Among the latter, only
      omegaB97X-V and omegaB97M-V can be recommended for ion-water clusters, as mean
      errors for other popular approaches (including omegaB97X-D3 and several Minnesota
      functionals) exceed 1 kcal/mol. Lastly, we examine clathrate-hydrate host/guest
      complexes whose mixture of hydrogen bonding and dispersion make them challenging
      tests for noncovalent quantum chemistry. Although the B97-D2 functional performs
      best for clathrate hydrates and has been previously recommended in other studies
      of these inclusion complexes, its performance for other systems examined here is
      quite poor. We are unable to find a functional whose accuracy is ?1 kcal/mol
      accuracy for both clathrate hydrates and ion-water clusters. However, the
      XSAPT(KS)+ aiD method with the nonadditive dispersion correction can achieve
      this, with a mean error for the clathrate hydrates of 0.3 kcal/mol.

PMID- 30199633
TI  - GPU-Accelerated Molecular Dynamics and Free Energy Methods in Amber18:
      Performance Enhancements and New Features.
AB  - We report progress in graphics processing unit (GPU)-accelerated molecular
      dynamics and free energy methods in Amber18. Of particular interest is the
      development of alchemical free energy algorithms, including free energy
      perturbation and thermodynamic integration methods with support for nonlinear
      soft-core potential and parameter interpolation transformation pathways. These
      methods can be used in conjunction with enhanced sampling techniques such as
      replica exchange, constant-pH molecular dynamics, and new 12-6-4 potentials for
      metal ions. Additional performance enhancements have been made that enable
      appreciable speed-up on GPUs relative to the previous software release.

PMID- 30199634
TI  - Enhanced Electrochemical Kinetics and Polysulfide Traps of Indium Nitride for
      Highly Stable Lithium-Sulfur Batteries.
AB  - Lithium-sulfur (Li-S) batteries are strongly considered as promising energy
      storage devices due to their high capacity and large theoretical energy density.
      However, the shuttle of polysulfides and their sluggish kinetic conversion in
      electrochemical processes seriously reduce the utilization of active sulfur,
      leading to a rapid capacity fading. Herein we introduced indium nitride (InN)
      nanowires into Li-S batteries through separator modification. Both the indium
      cation and electron-rich nitrogen atom of InN served as the polysulfide traps
      through strong chemical affinity. Meanwhile, the rapid electron transfer on the
      surface of InN accelerated the conversion of polysulfides in a working battery.
      The bifunction of InN nanowires effectively suppressed the shuttle effect.
      Therefore, Li-S batteries with InN-modified separators exhibit excellent rate
      performance and high stable cycling life with only 0.015% capacity decay per
      cycle after 1000 cycles, which affords fresh insights into the energy chemistry
      of high-stable Li-S batteries.

PMID- 30199635
TI  - Optimization of a Series of Mu Opioid Receptor (MOR) Agonists with High G Protein
      Signaling Bias.
AB  - While mu opioid receptor (MOR) agonists are especially effective as broad
      spectrum pain relievers, it has been exceptionally difficult to achieve a clear
      separation of analgesia from many problematic side effects. Recently, many groups
      have sought MOR agonists that induce minimal betaarrestin-mediated signaling
      because MOR agonist-treated betaarrestin2 knockout mice were found to display
      enhanced antinociceptive effects with significantly less respiratory depression
      and tachyphylaxis. Substantial data now exists to support the premise that G
      protein signaling biased MOR agonists can be effective analgesic agents. We
      recently showed that, within a chemical series, the degree of bias correlates
      linearly with the magnitude of the respiratory safety index. Herein we describe
      the synthesis and optimization of piperidine benzimidazolone MOR agonists that
      together display a wide range of bias (G/betaarr2). We identify structural
      features affecting potency and maximizing bias and show that many compounds have
      desirable properties, such as long half-lives and high brain penetration.

PMID- 30199636
TI  - Can Sanitation Technology Play a Role in User Perceptions of Resource Recovery?
      An Evaluation of Composting Latrine Use in Developing World Communities in
      Panama.
AB  - There remains a large unmet need for sanitation access throughout the world that
      compromises both human and environmental health. Opportunities exist to employ
      sanitation systems that better utilize and recover scarce resources from excreta
      such as water, energy, and nutrients. However, technologies such as a composting
      latrine may require more maintenance and close handling of feces compared to
      other sanitation technologies. This study aims to evaluate how use of on-site
      composting latrine technology and other demographic characteristics are
      associated with users' perceptions of excreta for resource recovery. Field
      observations and interviews of composting latrine users ( N = 201) and 200
      perceptions surveys were administered to composting and non-composting latrine
      users in Indigenous and Latino communities in Panama. Of the completed composting
      latrines, 78% were in use and 65% of these were used properly. Compost latrine
      design and operational factors identified to improve were: anal wash capability,
      desiccant supply, children usage, and clogging urine tubes. Demographic
      categories associated with positive perceptions toward resource recovery ( p <
      0.05) were ethnicity (14 out of 16 total statements) and sanitation type (11)
      then community origin (7), occupation (5), education (4), age (3), and gender
      (1).

PMID- 30199637
TI  - LIT-001, the First Nonpeptide Oxytocin Receptor Agonist that Improves Social
      Interaction in a Mouse Model of Autism.
AB  - Oxytocin (OT) and its receptor (OT-R) are implicated in the etiology of autism
      spectrum disorders (ASD), and OT-R is a potential target for therapeutic
      intervention. Very few nonpeptide oxytocin agonists have currently been reported.
      Their molecular and in vivo pharmacology remain to be clarified, and none of them
      has been shown to be efficient in improving social interaction in animal models
      relevant to ASD. In an attempt to rationalize the design of centrally active
      nonpeptide full agonists, we studied in a systematic way the structural
      determinants of the affinity and efficacy of representative ligands of the V1a
      and V2 vasopressin receptor subtypes (V1a-R and V2-R) and of the oxytocin
      receptor. Our results confirm the subtlety of the structure-affinity and
      structure-efficacy relationships around vasopressin/oxytocin receptor ligands and
      lead however to the first nonpeptide OT receptor agonist active in a mouse model
      of ASD after peripheral ip administration.

PMID- 30199639
TI  - pywindow: Automated Structural Analysis of Molecular Pores.
AB  - Structural analysis of molecular pores can yield important information on their
      behavior in solution and in the solid state. We developed pywindow, a python
      package that enables the automated analysis of structural features of porous
      molecular materials, such as molecular cages. Our analysis includes the cavity
      diameter, number of windows, window diameters, and average molecular diameter.
      Molecular dynamics trajectories of molecular pores can also be analyzed to
      explore the influence of flexibility. We present the methodology, validation, and
      application of pywindow for the analysis of molecular pores, metal-organic
      polyhedra, and some instances of framework materials. pywindow is freely
      available from github.com/JelfsMaterialsGroup/pywindow .

PMID- 30199638
TI  - QM/MM Calculations on Protein-RNA Complexes: Understanding Limitations of
      Classical MD Simulations and Search for Reliable Cost-Effective QM Methods.
AB  - Although atomistic explicit-solvent Molecular Dynamics (MD) is a popular tool to
      study protein-RNA recognition, satisfactory MD description of protein-RNA
      complexes is not always achieved. Unfortunately, it is often difficult to
      separate MD simulation instabilities primarily caused by the simple point-charge
      molecular mechanics (MM) force fields from problems related to the notorious
      uncertainties in the starting structures. Herein, we report a series of large
      scale QM/MM calculations on the U1A protein-RNA complex. This experimentally well
      characterized system has an intricate protein-RNA interface, which is very
      unstable in MD simulations. The QM/MM calculations identify several H-bonds
      poorly described by the MM method and thus indicate the sources of instabilities
      of the U1A interface in MD simulations. The results suggest that advanced QM/MM
      computations could be used to indirectly rationalize problems seen in MM-based MD
      simulations of protein-RNA complexes. As the most accurate QM method, we employ
      the computationally demanding meta-GGA density functional TPSS-D3(BJ)/def2-TZVP
      level of theory. Because considerably faster methods would be needed to extend
      sampling and to study even larger protein-RNA interfaces, a set of low-cost QM/MM
      methods is compared to the TPSS-D3(BJ)/def2-TZVP data. The PBEh-3c and B97-3c
      density functional composite methods appear to be suitable for protein-RNA
      interfaces. In contrast, HF-3c and the tight-binding Hamiltonians DFTB3-D3 and
      GFN-xTB perform unsatisfactorily and do not provide any advantage over the MM
      description. These conclusions are supported also by similar analysis of a simple
      HutP protein-RNA interface, which is well-described by MD with the exception of
      just one H-bond. Some other methodological aspects of QM/MM calculations on
      protein-RNA interfaces are discussed.

PMID- 30199640
TI  - Noncovalent Interactions between Molecular Hydrogen and the Alkali Fluorides: H
      H...F-M (M = Li, Na, K, Rb, Cs). High Level Theoretical Predictions and SAPT
      Analysis.
AB  - Various types of hydrogen bonds have been recognized during the past century. In
      this research, a new type of noncovalent interaction, the dipole-induced hydrogen
      bond formed between a hydrogen molecule and an alkali halide, H-H...F-M, is
      studied. Proposed by Zhang and co-workers ( Phys. Chem. Chem. Phys. 2015, 17,
      20361), these systems are extensively investigated initially using the "gold
      standard" CCSD(T) method in conjunction with augmented correlation-consistent
      polarized core-valence basis sets up to quadruple-zeta. The full triple
      excitations CCSDT method has been used to further refine the energies. Several
      properties including geometries, bond energies, vibrarional frequencies, charge
      distributions, and dipole moments have been reported. The earlier Zhang research
      considered only the linear H-H...F-M structures. However, we find these linear
      stationary points to be separated by very small barriers from the much lower
      lying bent C s structures. The CCSDT/aug-cc-pCVQZ(-PP) method predicts the
      dissociation energies for bent H-H...F-M (M = Li, Na, K, Rb, Cs) are 2.76, 2.96,
      3.00, 2.89, and 2.49 kcal mol-1, respectively, suggesting that the H...F hydrogen
      bond becomes gradually stronger when alkali metal M goes down the periodic table
      from Li to K but becomes slightly weaker for Rb and even more for Cs. This Li <
      Na < K > Rb > Cs order is consistent with that for the dipole moments for the
      isolated MF (M = Li, Na, K, Rb, Cs) diatomics. Symmetry adapted perturbation
      theory (SAPT) is used to understand these unusual noncovalent interactions.

PMID- 30199641
TI  - Driving Coordination Polymer Monolayer Formation by Competitive Reactions at the
      Air/Water Interface.
AB  - We have developed a novel approach enabling us to follow and facilitate the
      formation of two-dimensional coordination polymer monolayers directly at the
      air/water interface without the need of complex instrumentation. The method is
      based on the use of a surface active ligand that, when spread at the air/water
      interface, progressively undergoes hydrolysis with consequent gradual decrease in
      surface pressure. Notably, if the aqueous subphase contains metal ions capable of
      coordinating the ligand, coordination competes with hydrolysis, resulting in a
      lower surface pressure decrease. As a consequence, the formation of the
      coordination polymer monolayer can be verified simply by surface pressure
      measurements. Competition between hydrolysis and coordination was investigated as
      a function of the main experimental parameters affecting the two reactions,
      enabling the formation of stable coordination polymer monolayers with controlled
      density. Finally, the formation of continuous rigid 2D layers was confirmed by
      compression isotherms and ex situ morphological characterization. This work will
      simplify the verification of coordination polymer monolayer formation; thus, it
      will boost the synthesis of novel and innovative 2D materials.

PMID- 30199642
TI  - Stratification of Pulmonary Nodules Using Quantitative Iodine-Maps from Dual
      Energy CT.

PMID- 30199643
TI  - Lung Cancer Screening in a Safety-Net Hospital: Implications of Screening a Real
      World Population versus the National Lung Screening Trial.

PMID- 30199644
TI  - Relation Between Respiratory Mechanics, Inflammation, and Survival in
      Experimental Mechanical Ventilation.
AB  - RATIONALE: Low tidal volume ventilation might protect healthy lungs from
      volutrauma but lead to inflammation from other mechanisms, namely alveolar
      derecruitment and the ensuing alveolar collapse and reexpansion. OBJECTIVE: We
      hypothesized that the different mechanisms of low and high volume injury would be
      reflected in different mechanical properties being associated with development of
      pulmonary inflammation and mortality: an increase of hysteresis, reflecting
      progressive alveolar derecruitment, at low tidal volume; an increase of
      elastance, as a result of overdistension, at higher tidal volume. METHODS: Mice
      were allocated to "protective" (6 ml/kg) or injurious (15-20 ml/kg) tidal volume
      groups and ventilated for 16 hours or until death. We measured elastance,
      hysteresis, pulmonary IL-6, IL-1beta and MIP-2, wet-to-dry ratio and blood gases.
      MEASUREMENTS AND MAIN RESULTS: Survival was greater in the protective (60%) than
      injurious (25%) group. Non-survivors showed increased pulmonary cytokines,
      particularly in the injurious group, with the increase of elastance reflecting IL
      6 level. Survivors, instead, showed only modest increases of cytokines,
      independent of tidal volume and unrelated to the increase of elastance. No single
      lung strain threshold could discriminate survivors from non-survivors. Hysteresis
      increased faster in the protective group but, contrary to our hypothesis, its
      change was inversely related to the level of cytokines. CONCLUSIONS: In this
      model, significant mortality associated with pulmonary inflammation occurred even
      for strain values as low as ~0.8. Low tidal volume improved survival. The
      accompanying increase of hysteresis was not associated with greater inflammation.

PMID- 30199645
TI  - No Growth Disturbance After Trochleoplasty for Recurrent Patellar Dislocation in
      Adolescents With Open Growth Plates.
AB  - BACKGROUND:: Trochlear dysplasia is the most important risk factor for
      patellofemoral instability among adolescents; therefore, trochleoplasty to
      reshape the trochlear groove is the treatment of choice for patients with high
      grade trochlear dysplasia. However, in the presence of open growth plates, there
      is a potential risk of injury to the distal femoral growth plate and subsequent
      growth disturbance. As such, most authors do not recommend trochleoplasty for
      skeletally immature patients. The effect of trochleoplasty on femoral growth when
      performed before closure of the distal femoral physis remains unclear.
      HYPOTHESIS:: For patients with open growth plates and an expected growth <2
      years, trochleoplasty does not cause growth disturbance of the distal femur.
      STUDY DESIGN:: Case series; Level of evidence, 4. METHODS:: Eighteen consecutive
      adolescents (18 knees) with open physes and severe trochlear dysplasia underwent
      thin flap trochleoplasty. Pre- and postoperative radiographic examination
      included anteroposterior and lateral views to assess leg axis and patella alta. A
      preoperative radiograph of the left hand was performed to measure skeletal age.
      Magnetic resonance imaging was performed to evaluate trochlear dysplasia and
      tibial tubercle-trochlear groove distance. Evaluation included pre- and
      postoperative physical examination with evaluation of leg length and leg axis,
      Kujala score, and Tegner activity score. RESULTS:: The median age at the time of
      operation was 12.6 years (range, 12.2-13.3 years) for girls and 14.5 years (14.0
      15.4 years) for boys. The mean follow-up after operation was 2.3 years after
      surgery (range, 2.0-3.0 years). At follow-up for all patients, the growth plates
      of the knee were closed. Impairment of growth of the distal femur was found
      neither clinically nor radiographically. No recurrent dislocation occurred. The
      median Kujala score improved significantly from 67 (range, 54-75) preoperatively
      to 89.5 (range, 78-96) at follow-up ( P < .01). The median visual analog scale
      showed significant pre- to postoperative improvement from 5 (range, 3-7) to 1
      (range, 0-3) ( P < .01). The activity level according to the Tegner activity
      score did not change significantly. CONCLUSION:: In this study, trochleoplasty as
      a treatment for patellofemoral instability of patients with open physes and an
      expected growth of not more than 2 years showed good clinical results without
      redislocation and with no growth disturbance. Therefore, for selected adolescent
      patients with high-grade trochlear dysplasia, trochleoplasty can be safely
      performed up to 2 years before the projected end of growth.

PMID- 30199646
TI  - Graft Choice and the Incidence of Osteoarthritis After Anterior Cruciate Ligament
      Reconstruction: A Causal Analysis From a Cohort of 541 Patients.
AB  - BACKGROUND: Anterior cruciate ligament (ACL) reconstruction is important to
      prevent knee osteoarthritis. Neither of the 2 most common graft techniques-the
      patellar tendon (PT) or hamstring tendon (HS) graft-has demonstrated superiority
      in terms of the long-term osteoarthritis rate. HYPOTHESIS: Based on the
      International Knee Documentation Committee (IKDC) radiographic grading system, PT
      grafts decrease the incidence of osteoarthritis by providing better knee
      stability as compared with HS grafts over 12 years of follow-up. STUDY DESIGN:
      Cohort study; Level of evidence, 3. METHODS: All adults with a first ACL rupture
      who underwent surgery with a PT or HS graft technique between January 2002 and
      December 2003 were included in the 2014 French Society of Orthopedic Surgery and
      Traumatology Symposium database. Baseline characteristics were collected. The
      primary endpoint was the occurrence of moderate to severe osteoarthritis in each
      group. The secondary endpoints included clinical subjective evaluations by the
      IKDC score and Knee injury and Osteoarthritis Outcome Score. To control the
      differences in baseline characteristics, the data were analyzed with propensity
      score matching. RESULTS: In the cohort, 541 patients from 18 centers were
      included: 311 PT and 230 HS ACL reconstructions. The baseline characteristics
      were similar after inverse probability weighting treatment (IPWT). The occurrence
      of osteoarthritis was similar after IPWT (19.3% for PT and 19.6% for HS, P =
      .94). Age at surgery >29 years and IKDC osteoarthritis stage B at the index
      surgery were identified as risk factors for moderate to severe osteoarthritis.
      Most functional outcomes were significantly higher in the HS group; however, the
      difference between groups remained <10 points. Of the 106 patients who needed a
      medial meniscectomy, the proportion of patients with moderate to severe
      osteoarthritis was much higher in the HS group (43.5% vs 18.3%, P = .006).
      However, after IPWT, the difference was not statistically significant.
      CONCLUSION: At 12 years of follow-up, neither graft technique was superior to the
      other in terms of the rate of osteoarthritis.

PMID- 30199647
TI  - Circulating tumor cells as biomarkers in head and neck cancer: recent advances
      and future outlook.
AB  - INTRODUCTION: Assessment of circulating tumor cells (CTCs) in peripheral blood
      from solid cancer patients including head and neck squamous cell carcinoma
      (HNSCC) has proven useful for detection of subclinical disease that otherwise
      remains invisible for current staging techniques. Based on large cohort studies,
      diagnostic tests for enumeration of CTCs have been developed, which can be used
      for tumor staging, prognosis, treatment monitoring, and post-treatment
      surveillance. Areas covered: Here, we briefly summarize the history of CTC
      discovery. We review the current evidence of a diagnostic potential of CTCs in
      HNSCC. We present recent technical advancements in the tools for enrichment,
      detection, and molecular characterization of CTCs. We also discuss potential
      clinical applications of CTC detection for personalized treatment strategies.
      Expert commentary: Recent technical advances in the platforms for enrichment,
      detection, and comprehensive molecular characterization of CTC represent a great
      opportunity to improve our understanding in the biology of CTCs and will allow to
      expand the clinical utility of CTCs in HNSCC. Especially, HNSCC patients with
      recurrent/metastatic disease associated dismal prognosis and little improvement
      in treatment outcome over the past decade might benefit in the future from
      incorporation of CTC assays in clinical management.

PMID- 30199648
TI  - Sarcoidosis-associated Hospitalizations in the United States, 2002 to 2012.

PMID- 30199649
TI  - Effects of exogenous microbial inoculum on the structure and dynamics of
      bacterial communities in swine carcass composting.
AB  - Composting is a widely accepted method for the disposal of deceased livestock. It
      is a biological self-heating process during which animal carcasses are converted
      to fertilizer products. Additional inoculants can facilitate the composting
      progress. This study investigated how the addition of microbial inoculants could
      improve the composting effectiveness and could change the structure and dynamics
      of bacterial communities in the carcass composting process. Four strains of
      Bacillus were inoculated into the swine carcass composting piles. The groups with
      the additional inoculants showed a higher temperature in the thermophilic phase
      and higher germination indices in the composted products. The sequencing results
      showed that the dominant phyla were Proteobacteria, Firmicutes, and
      Actinobacteria, and the dominant classified genera were Brevibacterium and
      Bacillus. Canonical correlation analysis showed that temperature and moisture
      exerted a stronger influence on the bacterial community diversity. The
      interaction network of dominant genera and the abundance variation of the
      bacterial community demonstrated that the inoculated bacterial agent changed the
      structure of bacterial communities and enriched the diversity of the species due
      to antagonism and symbiosis among the dominant bacterial communities.

PMID- 30199650
TI  - Calculation Efficiencies for Mean Numerosity.
AB  - Relative numerosity is traditionally studied using texture pairs. Observers must
      decide which member of each pair has the greater total number of texture
      elements. In the present experiment, textures were segregated into nonoverlapping
      "sectors" containing between zero and four elements, and our observers were asked
      to select the texture containing the greater average number of texture elements
      (per sector). If observers were more sensitive to total numerosity than average
      numerosity, their performance (quantified by the just-noticeable Weber fraction)
      should have been better when the two textures occupied the same number of sectors
      than when they occupied unequal numbers of sectors. However, we recorded Weber
      fractions between 11% and 13% for all observers in all conditions. This
      performance was comparable with an otherwise-ideal observer whose decisions were
      based on between three and five sectors in each texture. We conjecture that
      traditional numerosity discriminations are based on similarly small numbers of
      element clusters.

PMID- 30199651
TI  - Development of an Automated UV Irradiation Device for Microbial Cell Culture.
AB  - Ultraviolet (UV) mutagenesis is a widely used technique to increase bacterial
      mutation rates in laboratory experiments. UV mutagenesis requires fine regulation
      of UV dose, because the number of dead cells increases exponentially as the dose
      increases. Ignoring this hazard can cause extinction of UV-exposed populations.
      Therefore, an automated system that cooperatively conducts both growth
      measurement and UV irradiation is needed for efficient UV mutagenesis
      experiments. To address this task, we constructed an automated UV irradiation
      device for microbial cell culture. This device can measure cell density and
      irradiate the bacterial cells with UV light automatically according to the state
      of cell growth. We demonstrated that this growth feedback control avoided
      extinction and enabled accumulation of mutations in bacterial genomes at a rapid
      rate for a long period. Whole-genome sequencing revealed the high accumulation
      rate, neutrality, and spectrum of UV-induced mutations. These characteristics
      were all consistent with those obtained by manual UV irradiation. These results
      indicate that our automated device is useful in accelerating mutation
      accumulation over a long duration.

PMID- 30199652
TI  - The Injurious Effects of Elevated or Non-Elevated Respiratory Rate during
      Mechanical Ventilation.
AB  - Respiratory rate is one of the key variables we set and monitor during mechanical
      ventilation. As part of our increasing efforts to optimise mechanical
      ventilation, it is prudent that we expand our understanding of the potential
      harmful effects not only of volume and pressures, but also of respiratory rate.
      The mechanisms by which respiratory rate may become injurious during mechanical
      ventilation can be distinguished in two broad categories. In the first well
      recognised category, concerning both controlled and assisted ventilation, the
      respiratory rate per se may promote ventilator-induced lung injury, dynamic
      hyperinflation, ineffective efforts and respiratory alkalosis. It may also be
      misinterpreted as distress delaying the weaning process. In the second category,
      which concerns only assisted ventilation, the respiratory rate may induce injury
      in a less apparent way, by remaining relatively quiescent while being challenged
      by chemical feedback. By responding minimally to chemical feedback, respiratory
      rate leaves the control of minute ventilation almost exclusively to inspiratory
      effort. In such cases, when assist is high, weak inspiratory efforts promote
      ineffective triggering, periodic breathing and diaphragmatic atrophy. Conversely,
      when assist is low, diaphragmatic efforts are intense and increase the risk for
      respiratory distress, asynchronies, ventilator-induced lung injury, diaphragmatic
      injury, and cardiovascular complications. This review thoroughly presents the
      multiple mechanisms by which respiratory rate may induce injury during mechanical
      ventilation, drawing the attention of critical care physicians to the potential
      injurious effects of respiratory rate insensitivity to chemical feedback during
      assisted ventilation.

PMID- 30199653
TI  - Trichoderma cyanodichotomus sp. nov., a new soil-inhabiting species with a
      potential for biological control.
AB  - During a biodiversity survey of Trichoderma (Ascomycota, Hypocreales,
      Hypocreaceae) in coastal and lake wetlands of China, a new species, Trichoderma
      cyanodichotomus, was isolated from Dongting Lake wetland of Hunan province. The
      strain TW21990-1 was characterized as having two types of conidia and producing a
      distinct blue-green pigment on potato dextrose agar and cornmeal dextrose agar.
      The taxonomic position was analyzed using three molecular markers, internal
      transcribed spacer rDNA, translation elongation factor 1-alpha, and RNA
      polymerase II subunit B, revealing less than 95.0% homology with all known
      Trichoderma species. The combined phylogenetic tree further identified T.
      cyanodichotomus as an independent subgroup belonging to Section Pachybasium, with
      no close relatives. In vitro antagonistic activity by dual-culture assay
      exhibited broad inhibition against various plant pathogens, including
      Botryosphaeria dothidea, Pythium aphanidermatum, Rhizoctonia solani, and
      Verticillium dahliae. In addition, TW21990-1 demonstrated moderate hydrolase
      activity of cellulase, chitinase, beta-1,3-glucanase, and protease, which might
      be involved in mycoparasitism. Greenhouse experiments showed strong biocontrol
      effects against tomato damping-off incited by P. aphanidermatum, together with
      increased seedling height and weight gain. The identification of T.
      cyanodichotomus will provide useful information for sufficient utilization of
      fungal resources.

PMID- 30199654
TI  - Berberine Ameliorates Periodontal Bone Loss by Regulating Gut Microbiota.
AB  - Postmenopausal osteoporosis (PMO) is a risk factor for periodontitis, and current
      therapeutics against PMO prevent the aggravated alveolar bone loss of
      periodontitis in estrogen-deficient women. Gut microbiota is recognized as a
      promising therapeutic target for PMO. Berberine extracted from Chinese medicinal
      plants has shown its effectiveness in the treatment of metabolic diseases such as
      obesity and diabetes via regulating gut microbiota. Here, we hypothesize that
      berberine ameliorates periodontal bone loss by improving the intestinal barriers
      by regulating gut microbiota under an estrogen-deficient condition. Experimental
      periodontitis was established in ovariectomized (OVX) rats, and the OVX
      periodontitis rats were treated with berberine for 7 wk before sacrifice for
      analyses. Micro-computed tomography and histologic analyses showed that berberine
      treatment significantly reduced alveolar bone loss and improved bone metabolism
      of OVX-periodontitis rats as compared with the vehicle-treated OVX-periodontitis
      rats. In parallel, berberine-treated OVX-periodontitis rats harbored a higher
      abundance of butyrate-producing gut microbiota with elevated butyrate generation,
      as demonstrated by 16S rRNA sequencing and high-performance liquid chromatography
      analysis. Berberine-treated OVX-periodontitis rats consistently showed improved
      intestinal barrier integrity and decreased intestinal paracellular permeability
      with a lower level of serum endotoxin. In parallel, IL-17A-related immune
      responses were attenuated in berberine-treated OVX-periodontitis rats with a
      lower serum level of proinflammatory cytokines and reduced IL-17A+ cells in
      alveolar bone as compared with vehicle-treated OVX-periodontitis rats. Our data
      indicate that gut microbiota is a potential target for the treatment of estrogen
      deficiency-aggravated periodontal bone loss, and berberine represents a promising
      adjuvant therapeutic by modulating gut microbiota.

PMID- 30199655
TI  - Temperature Control after Cardiac Arrest. When to Start? How Long? How Cold?

PMID- 30199656
TI  - Refined Immunochemical Characterization in Healthy Dog Skin of the Epidermal
      Cornification Proteins, Filaggrin, and Corneodesmosin.
AB  - Filaggrin (FLG) and corneodesmosin (CDSN) are two key proteins of the human
      epidermis. FLG loss-of-function mutations are the strongest genetic risk factors
      for human atopic dermatitis. Studies of the epidermal distribution of canine FLG
      and CDSN are limited. Our aim was to better characterize the distribution of FLG
      and CDSN in canine skin. Using immunohistochemistry on beagle skin, we screened a
      series of monoclonal antibodies (mAbs) specific for human FLG and CDSN. The cross
      reactive mAbs were further used using immunoelectron microscopy and Western
      blotting. The structure of canine CDSN and FLG was determined using publicly
      available databases. In the epidermis, four anti-FLG mAbs stained keratohyalin
      granules in the granular keratinocytes and corneocyte matrix of the lower
      cornified layer. In urea-extracts of dog epidermis, several bands corresponding
      to proFLG and FLG monomers were detected. One anti-CDSN mAb stained the cytoplasm
      of granular keratinocytes and cells of both the inner root sheath and medulla of
      hair follicles. Dog CDSN was located in lamellar bodies, in the extracellular
      parts of desmosomes and in corneodesmosomes. A protein of 52 kDa was
      immunodetected. Genomic DNA analysis revealed that the amino acid sequence and
      structure of canine and human CDSN were highly similar.

PMID- 30199658
TI  - Risk Factors for Post-Traumatic Stress Disorder Symptoms in Surrogate Decision
      Makers of Patients with Chronic Critical Illness.
AB  - RATIONALE: Chronically critically ill patients are often dependent on family
      members for surrogate decision-making, and these surrogates are at high risk for
      emotional distress. We hypothesized that patient- and surrogate-specific risk
      factors for surrogate post-traumatic stress disorder (PTSD) symptoms can be
      identified early in the course of chronic critical illness. OBJECTIVES: To
      identify risk factors for PTSD symptoms in surrogate decision-makers of
      chronically critically ill patients. METHODS: We performed a secondary analysis
      of the database from a multicenter randomized trial of a communication
      intervention for chronic critical illness patients and surrogates. Variables
      preselected for plausible mechanism for increasing PTSD symptoms and identifiable
      by Day 10 of mechanical ventilation were included in the analysis for association
      with surrogate PTSD symptoms at 90 days, as measured by the Impact of Events
      Score-Revised (IES-R). Patient factors included demographics, insurance status,
      baseline functional status, chronic comorbidities, illness severity, and presence
      of advance directive. Surrogate variables included demographics, education level
      and employment, religion, relationship to patient, and Hospital Anxiety and
      Depression Scale score measured at enrollment. Multivariable linear regression
      models were then constructed for 26 potential risk factors, including
      biologically or mechanistically plausible confounders for each, with IES-R score
      as the outcome. All models were adjusted for multiple respondents, using a mixed
      model, considering the patients as a random factor. RESULTS: Our analysis
      included 306 surrogates for 224 patients. A total of 49% of patients were female,
      and mean age was 59 years (95% confidence interval [CI], 56.4-60.7). A total of
      71% of surrogates were female, and mean age was 51 years (95% CI, 49.3-52.4).
      After examining each potential risk factor in a separate multivariable model,
      only Day-10 surrogate Hospital Anxiety and Depression Scale score (beta
      coefficient = 1.02; 95% CI, 0.73-1.30) and patient unresponsiveness (beta
      coefficient = 8.39; 95% CI, 0.83-15.95) were associated with higher IES-R scores.
      CONCLUSIONS: Among surrogate decision-makers for chronically critically ill
      patients, high anxiety and depression scores and patient unresponsiveness on or
      near Day 10 of mechanical ventilation are risk factors for PTSD symptoms at 90
      days.

PMID- 30199657
TI  - Omega-3 Fatty Acids and Genome-wide Interaction Analyses Reveal DPP10-Pulmonary
      Function Association.
AB  - RATIONALE: Omega-3 poly-unsaturated fatty acids (n-3 PUFAs) have anti
      inflammatory properties that could benefit adults with comprised pulmonary
      health. OBJECTIVE: To investigate n-3 PUFA associations with spirometric measures
      of pulmonary function tests (PFTs) and determine underlying genetic
      susceptibility. METHODS: Associations of n-3 PUFA biomarkers (alpha-linolenic
      acid, eicosapentaenoic acid, docosapentaenoic acid [DPA], and docosahexaenoic
      acid [DHA]) were evaluated with PFTs (forced expiratory volume in the first
      second [FEV1], forced vital capacity [FVC], and [FEV1/FVC]) in meta-analyses
      across seven cohorts from the Cohorts for Heart and Aging Research in Genomic
      Epidemiology Consortium (N=16,134 of European or African ancestry). PFT
      associated n-3 PUFAs were carried forward to genome-wide interaction analyses in
      the four largest cohorts (N=11,962) and replicated in one cohort (N=1,687).
      Cohort-specific results were combined using joint 2 degree-of-freedom (2df) meta
      analyses of single nucleotide polymorphism (SNP) associations and their
      interactions with n-3 PUFAs. RESULTS: DPA and DHA were positively associated with
      FEV1 and FVC (P<0.025), with evidence for effect modification by smoking and by
      sex. Genome-wide analyses identified a novel association of rs11693320-an
      intronic DPP10 SNP-with FVC when incorporating an interaction with DHA, and the
      finding was replicated (P2df=9.4*10-9 across discovery and replication cohorts).
      The rs11693320-A allele (frequency~80%) was associated with lower FVC
      (PSNP=2.1*10-9; betaSNP= -161.0mL), and the association was attenuated by higher
      DHA levels (PSNP*DHA interaction=2.1*10-7; betaSNP*DHA interaction=36.2mL).
      CONCLUSIONS: We corroborated beneficial effects of n-3 PUFAs on pulmonary
      function. By modeling genome-wide n-3 PUFA interactions, we identified a novel
      DPP10 SNP association with FVC that was not detectable in much larger studies
      ignoring this interaction.

PMID- 30199659
TI  - Corrigendum to "Rediscovery of Otto Frank's contribution to science" Journal of
      Molecular and Cellular Cardiology (JMCC) Volume 119, June 2018, Pages 96-103, and
      front cover.

PMID- 30199660
TI  - Hypertension.

PMID- 30199661
TI  - Where do broken hearts go?

PMID- 30199662
TI  - The art of immunisation.

PMID- 30199663
TI  - The art of priority setting.

PMID- 30199666
TI  - Hand functions in patients with schizophrenia: A clinical comparison with bipolar
      disorder and healthy subjects.
AB  - OBJECTIVE: Failure to achieve expected level of motor functioning may be a
      significant contributor to social withdrawal and further attenuation of life
      quality in patients with schizophrenia. Hand functioning is one of the most
      crucial entities in that manner. This study aimed to reveal this question by
      means of comparing patients with schizophrenia and bipolar disorder who are
      receiving similar antipsychotic psychopharmacological agents along with healthy
      control subjects. METHODS: 99 patients with schizophrenia were compared to 40
      patients with bipolar disorder matched according to the received pharmacotherapy
      comprising similar antipsychotics and 81 medication-free socio-demographically
      matched healthy control subjects. The materials were Hand Functional Index (HFI),
      Duruoz Hand Index (DHI), Scale for the Assessment of Negative Symptoms (SANS),
      Scale for the Assessment of Positive Symptoms (SAPS) along with clinical
      characteristics. RESULTS: Difference in total scores of DHI and HFI between
      schizophrenia, bipolar disorder and control groups were extremely significant (p
      < 0.001). Further post-hoc subgroup analysis revealed that patients with
      schizophrenia demonstrated higher scores of HFI indicating worse performance when
      compared to both bipolar disorder and control group. Significantly higher scores
      of DHI in patients with schizophrenia than healthy controls were noted.
      CONCLUSION: Independent from the impact of the medication use, impairment in hand
      functions was found to be more frequently seen in schizophrenia when compared to
      patients with bipolar disorder and healthy subjects. It is evident that hand
      function impairment is seen independent from psychopharmacological side effect,
      and is recommended to be assessed as a possible preventable and retractable
      manifestation of schizophrenia.

PMID- 30199665
TI  - A latent profile analysis of age of onset in pathological skin picking.
AB  - BACKGROUND: Pathological Skin Picking (PSP) may begin at any age, but the most
      common age of onset is during adolescence. Age of onset is a potentially useful
      clinical marker to delineate subtypes of psychiatric disorders. The present study
      sought to examine empirically defined age of onset groups in adults with PSP and
      assess whether groups differed on clinical characteristics. METHOD: Participants
      were 701 adult respondents to an internet survey, who endorsed recurrent skin
      picking with tissue damage and impairment. Latent profile analysis (LPA) was
      conducted to identify subtypes of PSP based on age of onset. Then subgroups were
      compared on demographic and clinical characteristics. RESULTS: The best fitting
      LPA model was a two-class solution comprised of a large group with average age of
      onset in adolescence (n = 650; 92.9% of the sample; Mean age of onset = 13.6
      years) and a small group with average onset in middle adulthood (n = 50; 7.1% of
      the sample; Mean age of onset = 42.8 years). Relative to the early onset group,
      the late onset group reported significantly less focused picking, less skin
      picking-related impairment, lower rates of co-occurring body-focused repetitive
      behaviors, and trends towards reduced family history of PSP. Individuals in the
      late onset group also reported increased rates of comorbid depression, anxiety
      and posttraumatic stress disorder, and were more likely to report that initial
      picking onset seemed related to or followed depression/anxiety and physical
      illness. CONCLUSION: Findings suggest the presence of two distinct PSP age of
      onset groups: (1) an early onset group with average onset in adolescence,
      clinical characteristics suggestive of greater picking-related burden and
      familiality, and a profile more representative of the general PSP population; and
      (2) a late onset group with average onset in middle adulthood, increased co
      occurring affective and trauma conditions, and initial onset associated with or
      following other mental health and physical problems. Future replication is needed
      to assess the validity and clinical utility of these subgroups.

PMID- 30199667
TI  - What is cold-related mortality? A multi-disciplinary perspective to inform
      climate change impact assessments.
AB  - BACKGROUND: There is a growing discussion regarding the mortality burdens of hot
      and cold weather and how the balance between these may alter as a result of
      climate change. Net effects of climate change are often presented, and in some
      settings these may suggest that reductions in cold-related mortality will
      outweigh increases in heat-related mortality. However, key to these discussions
      is that the magnitude of temperature-related mortality is wholly sensitive to the
      placement of the temperature threshold above or below which effects are modelled.
      For cold exposure especially, where threshold effects are often ill-defined,
      choices in threshold placement have varied widely between published studies, even
      within the same location. Despite this, there is little discussion around
      appropriate threshold selection and whether reported associations reflect true
      causal relationships - i.e. whether all deaths occurring below a given
      temperature threshold can be regarded as cold-related and are therefore likely to
      decrease as climate warms. OBJECTIVES: Our objectives are to initiate a
      discussion around the importance of threshold placement and examine evidence for
      causality across the full range of temperatures used to quantify cold-related
      mortality. We examine whether understanding causal mechanisms can inform
      threshold selection, the interpretation of current and future cold-related health
      burdens and their use in policy formation. METHODS: Using Greater London data as
      an example, we first illustrate the sensitivity of cold related mortality to
      threshold selection. Using the Bradford Hill criteria as a framework, we then
      integrate knowledge and evidence from multiple disciplines and areas- including
      animal and human physiology, epidemiology, biomarker studies and population level
      studies. This allows for discussion of several possible direct and indirect
      causal mechanisms operating across the range of 'cold' temperatures and lag
      periods used in health impact studies, and whether this in turn can inform
      appropriate threshold placement. RESULTS: Evidence from a range of disciplines
      appears to support a causal relationship for cold across a range of temperatures
      and lag periods, although there is more consistent evidence for a causal effect
      at more extreme temperatures. It is plausible that 'direct' mechanisms for cold
      mortality are likely to occur at lower temperatures and 'indirect' mechanisms
      (e.g. via increased spread of infection) may occur at milder temperatures.
      CONCLUSIONS: Separating the effects of 'extreme' and 'moderate' cold (e.g.
      temperatures between approximately 8-9  degrees C and 18  degrees C in the UK)
      could help the interpretation of studies quoting attributable mortality burdens.
      However there remains the general dilemma of whether it is better to use a lower
      cold threshold below which we are more certain of a causal relationship, but at
      the risk of under-estimating deaths attributable to cold.

PMID- 30199668
TI  - Wearable sensors for multifactorial personal exposure measurements - A ranking
      study.
AB  - Individuals are simultaneously exposed to multiple environmental stressors during
      their daily life. Studies of adverse health effects and their etiology as well as
      recommendations for a healthier life style demand for an assessment of
      multifactorial personal exposure, according to the exposome concept. A challenge
      is to record exposure while people are moving in heterogeneous urban
      environments. Therefore wearable sensor technologies are becoming a promising way
      to measure personal exposure continuously: indoors, outdoors and even on the
      move. So far, studies which test the accuracy and usability of wearable sensors
      for multiple stressors are lacking. Performance evaluations are important and
      should take place beforehand, especially to ensure the success of citizens
      oriented studies. For the first time we rigorously examined the accuracy and
      application suitability of wearable sensors for acoustic noise, heat (temp),
      particle number counts (PNC) and geo-location (GPS) in different environments. We
      present an extensive device inter-comparison and a ranking of the sensors based
      on performance measures, Taylor diagrams, Bland-Altman plots, and ease-of-use
      aspects. The sensors showed moderate to high correlations with precision
      reference devices (r = 0.4-0.99). Differences between errors outdoors and indoors
      suggest that environmental conditions have impact upon the accuracy of the
      sensors. Reaction time, recording interval, and sensor ventilation are features
      that play a crucial role for both ease-of-use and accuracy. We conclude with a
      final performance () ranking: (GPS) >  (noise) >  (temp) >  (PNC). The results
      are relevant for future epidemiological studies of multifactorial exposure of
      individuals and their health and should guide the selection of wearables when
      persons are involved that are technically untaught. Inferences from
      multifactorial data are based on the performance of all sensors and the weakest
      chain links are PNC and temp sensors for which our article recommends urgent
      improvements.

PMID- 30199669
TI  - Resource limitation of soil microbes in karst ecosystems.
AB  - Knowledge about resource limitation to soil microbes is crucial for understanding
      ecosystem functions and processes, and for predicting ecosystem responses to
      global changes as well. Karst ecosystems are widespread in the world, and play a
      key role in regulating the global climate, however, the patterns of and
      mechanisms underlying microbial resource limitation in karst ecosystems remain
      poorly known. Here we investigated the microbial resource limitation in a karst
      region, by selecting four main land-use types, i.e. cropland, grassland,
      shrubland and secondary forest, in areas underlain by two lithology types, i.e.
      dolomite and limestone, in southwest China. Ecoenzymatic stoichiometry was used
      as an indicator of microbial resource limitation. Overall, soil microbes in karst
      ecosystems were more limited by carbon and phosphorus, rather than by nitrogen.
      Further analyses revealed that the patterns of carbon and phosphorus limitation
      were different among land-use or lithology types. Microbial carbon limitation was
      greatest in cropland and forest but lowest in grassland, and was greater under
      dolomite than under limestone. Microbial phosphorus limitation decreased from
      secondary forest to cropland under dolomite areas, but showed no difference among
      ecosystem types under limestone areas, indicating that lithology controls the
      pattern of microbial phosphorus limitation along the post-agriculture succession.
      Our study describes a general pattern of microbial resource limitation in karst
      ecosystems, and we suggest that lithology may provide a new mechanism for
      explaining the variations of microbial resource limitation along the post
      agriculture succession in different regions.

PMID- 30199670
TI  - Phosphorus removal by application of natural and semi-natural materials for
      possible recovery according to assumptions of circular economy and closed circuit
      of P.
AB  - In the last few years the idea of circular economy has become essential. Thus,
      designing methods of nutrients removal should be based on using materials that
      make it possible to recover those nutrients. Recently, methods applied in
      wastewater treatment plants cannot provide optimal results; moreover, the
      application of commercial coagulants like ferric chloride and polyaluminum
      chloride can cause difficulties in potential recovery of phosphorus from sludge.
      Sorption materials, both natural and modified, are appearing as successful for
      wastewater treatment, especially for treatment wetland effluent. To pursue
      circular economy principles, the capacity of waste materials needs to be tested
      with regard to nutrients removal. If in addition a possibility to recover them
      appears, it will be possible to close the circuit. The aim of the investigation,
      according to HELCOM and EU Water Framework Directive recommendations, was to
      explore the possibility of ensuring good and stable quality of effluent by the
      application of natural materials for phosphorous removal with possible minimum
      energy and material consumption. The objective was to determine the sorption
      capacity of two selected materials (waste material and chemically modified
      material) in steady conditions. The research focused also on the time of mixing,
      a period of sedimentation of absorbent materials, and the influence of used
      materials on the basic parameters of the solution: pH, temperature, total
      suspended solids, conductivity, turbidity, and color. M1 was a waste material
      after thermal treatment of carbonate-siliceous rock in temperature above 700 
      degrees C (Rockfos(r)). Material M2 was lanthanum-modified bentonite, a material
      of anthropogenic origin. Both selected materials have shown a high ability to
      reduce phosphates concentration in synthetic wastewater. Sorption capacity of
      materials M1 and M2 were 45.6 mg/g and 5.6 mg/g, respectively.

PMID- 30199671
TI  - Analysis of water vapor effects on aerosol properties and direct radiative
      forcing in China.
AB  - The effects of column water vapor (CWV) on aerosol optical properties, radiative
      effects and classification are studied by using aerosol and CWV data from eight
      Aerosol Robotic Network (AERONET) sites in China: Beijing, XiangHe, Shouxian,
      Taihu, Hong_Kong, Zhongshan_Univ, SACOL, and Mt_WLG, which represents 5 distinct
      aerosol climatologies in China. Contrast in correlations between aerosol optical
      depth (AOD) and CWV is found. High correlation coefficient (R) ranging from 0.63
      0.94 is observed at Beijing and XiangHe (North China Plain), SACOL (Northwest
      China) and Mt_WLG (the Tibetan Plateau). R values at stations in the Middle-East
      China (Shouxian and Taihu) are within 0.32-0.45. AOD shows poor correlation to
      CWV in Southeast China (R at Hong_Kong and Zhongshan_Univ of 0.15 and 0.27). At
      most sites, the asymmetry (ASYM) of fine-mode aerosol increases with CWV with R
      larger than ~0.4. Aerosol direct radiative forcing efficiency (ADRFE) at the
      bottom of the atmosphere (BOA) is affected by CWV, with R >~0.5 over the north
      and Middle-East China sites. The statistic results show that an increase of CWV
      by 0.1 cm could result in enhancements of ADREF at the BOA by about 1.1-2.8 W m-2
      at all the sites except Mt_WLG. The aerosol classification shows that the mix
      small aerosol type is always dominated under the high CWV air. The clusters of
      back-trajectories with relative humidity (RH) from Hybrid Single-Particle
      Lagrangian Integrated Trajectory (HYSPLIT) model indicate that the air mass with
      high RH is often from south and east directions. The influence of CWV on aerosol
      properties is mainly shown in the properties of fine mode aerosol, which needs to
      be considered in the study of aerosol radiative forcing and climate effects.

PMID- 30199672
TI  - Cork as a sustainable carbon source for nature-based solutions treating
      hydroponic wastewaters - Preliminary batch studies.
AB  - Reusing by-products is an important strategy to ensure the preservation of
      natural capital and climate change mitigation. This study aimed at evaluating the
      potential of cork granulates, a by-product of winery industry, as an organic
      carbon (OC) source for the treatment of hydroponic wastewaters. First, chemical
      characterization was performed and discussed. Secondly, batch studies were
      performed using synthetic hydroponic wastewater to understand the role of
      particle size (PS), pH and contact time (CT) on the release of OC. The suberin is
      the major compound, representing >50%. It was noticed that a variance on the
      content of suberin across species, within the same species and depending on the
      extraction part (belly, cork and back) could be expected. >60% of the sample is
      composed by carbon while <1% was nitrogen (high C:N ratio), indicating a low risk
      of releasing organic nitrogen. The statistical results suggested that the main
      effect of PS on the release of OC is greater than both, CT and pH. The chemical
      release of OC gets slower with time, being this effect greater as the PS
      increase. Moreover, estimations showed that using the 4 mm PS, the amount of
      water treated would be twice the amount if the 8 mm PS had been used. The PS
      seems to play an important role at design nature-based solutions (NBS) focused on
      denitrification. The surface response methodology indicates a significant
      negative interaction between CT and PS suggesting that the mathematical model
      could be used for further optimization studies. The reuse of organic by-products
      as filter media seems to be an economic and environmentally friendly alternative
      to enhance denitrification in NBS, while preserving natural capital. However,
      further real scale and long-term experiments are needed to validate cork's
      potential as an "internal" OC source for NBS.

PMID- 30199673
TI  - Characteristics and oxidative potential of atmospheric PM2.5 in Beijing: Source
      apportionment and seasonal variation.
AB  - : PM2.5 (particulate matter with the aerodynamic diameter Dp < 2.5 MUm) was
      hypothesized to generate reactive oxygen species (ROS) and induce oxidative
      stress associated with inflammation and cardiovascular diseases. In the current
      study, PM2.5 concentrations, water-soluble ions and elements, carbonaceous
      components and ROS activity characterized by the dithiothreitol (DTT) assay were
      determined for the PM2.5 samples collected in Beijing, China, over a whole year.
      Source apportionments of PM2.5 and DTT activity were also performed. The mean +/-
      standard deviation of PM2.5, DTTm (mass-normalized DTT activity) and DTTv (volume
      normalized DTT activity) were 113.8 +/- 62.7 MUg.m-3, 0.13 +/- 0.10 nmol.MUg
      1.min-1 and 12.26 +/- 6.82 nmol.m-3.min-1, respectively. The seasonal averages of
      DTTm and DTTv exhibited peak values during the local summer. Organic carbon (OC),
      NO3-, SO42-, NH4+ and elemental carbon (EC) were the dominant components in the
      constituents tested. Higher concentrations of carbonaceous components occurred in
      autumn and winter compared with spring and summer. Based on the positive matrix
      factorization model (PMF), the simulation results of source apportionment for
      PM2.5 in Beijing, obtained using the annual data, identified the main categories
      as follows: dust, coal combustion, secondary sulfate and industrial emissions,
      vehicle emissions and secondary nitrates. Most detected constituents exhibited
      significantly positive correlations with DTTv (p < 0.01). The results
      corresponding to multiple linear regression (MLR) between DTTv activity and
      source contribution to PM2.5 manifested the sensitivity sequence of DTTv activity
      for the resolved sources as vehicle emissions > secondary sulfate and industrial
      emissions > coal combustion > dust. CAPSULE: Based on a descending sequence of
      relative contribution, the diagnostic sources of DTTv activity in PM2.5 from
      Beijing included primarily vehicle emissions, secondary sulfates and industrial
      emissions, coal combustion, and dust.

PMID- 30199674
TI  - Linkages between aerosol pollution and planetary boundary layer structure in
      China.
AB  - China suffers from high levels of PM2.5 pollution, which is often exacerbated by
      unfavorable planetary boundary layer (PBL) structures. Partly due to a lack of
      appropriate observations, the PBL-aerosol linkages in China are not clearly
      understood. Thus, we investigated these linkages from a national perspective
      using sounding data collected from 2014 to 2017. Correlation analyses revealed a
      significant anti-correlation between monthly boundary layer height (BLH) and
      aerosol pollution that was ubiquitous across China, indicating the important role
      of the PBL in regulating the seasonal variations of pollution in China. Besides,
      the day-to-day variations in pollution were modulated by the daily variabilities
      in the PBL structure. During winter, highly polluted days in most of the Chinese
      cities studied were associated with a low BLH, strong thermal stability, and weak
      PBL winds. In the North China Plain and Northeast China, the wintertime heavy
      pollution was often related to southerly winds and moister PBL. This study has
      important implications for understanding the crucial role that the PBL plays in
      modulating aerosol pollution in China.

PMID- 30199676
TI  - Nitrogen and phosphorus enrichment accelerates soil organic carbon loss in alpine
      grassland on the Qinghai-Tibetan Plateau.
AB  - Anthropogenic activities have substantially increased soil nutrient availability,
      which in turn affects ecosystem processes and functions, especially in nutrient
      limited ecosystems such as alpine grasslands. Although considerable efforts have
      been devoted to understanding the responses of plant productivity and community
      composition to nitrogen (N) and phosphorus (P) enrichment, the nutrient
      enrichment effects on soil organic carbon (SOC) and microbial functions are not
      well understood. A four-year field experiment was established to evaluate the
      influence of continuous N and P enrichment on plant growth and SOC content in an
      alpine grassland of the Qinghai-Tibetan Plateau. The study included four
      treatments: Control without addition, N addition, P addition, and N plus P
      addition. N addition strongly increased aboveground plant biomass and decreased
      species richness by promoting growth of the dominant grasses species. In
      contrast, N and P enrichment significantly decreased SOC, especially the
      recalcitrant organic C content in the surface layer (0-10 cm) by reducing the
      slow C pool and enlarging the active C pool. Microbial biomass and activities of
      C-degrading enzymes (beta-glucosidase, cellulase and polyphenol oxidase) and an N
      degrading enzyme (chitinase) increased with nutrient inputs. The CO2 emissions
      during a 300 d incubation period were positively correlated with the cellulase
      and chitinase activities, while the slow C pool was negatively correlated with
      the cellulase and polyphenol oxidase activities. Consequently, N and P enrichment
      accelerated decomposition of the recalcitrant C by stimulating microbial growth
      and increasing enzyme activities, leading to negative impacts on soil C
      sequestration. Overall, the results indicate that alpine grassland soils of the
      Qinghai-Tibetan Plateau may be changing from a C sink to a C source under
      increasing N and P availability, and improvement of alpine grassland management
      through nutrient inputs should consider not only the aboveground biomass for
      grazing, but also the soil C sequestration and ecosystem functioning.

PMID- 30199675
TI  - Hybrid constructed wetlands for the treatment of wastewater from a fertilizer
      manufacturing plant: Microcosms and field scale experiments.
AB  - Wastewater from a fertilizer manufacturing plant requires improvement prior to
      its environmental disposal. Ammonium is the critical contaminant to be removed.
      The aim of this study was to evaluate the feasibility of using free water surface
      wetlands (FWSWs), horizontal subsurface flow wetlands (HSSFWs), and their
      combination in hybrid wetlands (HWs) for the final treatment of wastewater with
      high ammonium concentration from a fertilizer manufacturing plant. Substrates and
      macrophytes were evaluated in microcosm experiments during three months. There
      were no significant differences in contaminant removal among HSSFWs with LECA or
      FWSWs planted with Typha domingensis or Canna indica. In a second stage, two
      configurations of pilot-scale HWs were constructed at the manufacturing
      facilities. Configuration A: HSSFW(A1)-FWSW(A2) and Configuration B: FWSW(B1)
      HSSFW(B2) were evaluated during 12 months. There were no significant differences
      in contaminant removal (%) between the two configurations of HWs for COD (A: 74.5
      +/- 12.2/B: 81.5 +/- 9.4), ammonium (A: 59.5 +/- 17.5/B: 57.9 +/- 21.4), nitrite
      (A: 79.8 +/- 24.2/B: 80.6 +/- 16.8) and dissolved inorganic nitrogen (DIN) (A:
      59.4 +/- 17.3/B: 50.3 +/- 24.4). However, nitrate concentration (9.83 +/- 3.11 mg
      N L-1) was significantly lower after Configuration A than after Configuration B
      (18.8 +/- 5.2 mg N L-1). Comparing FWSWs and HSSFWs, they did not present
      significant differences in ammonium removal, while FWSWs presented the highest
      DIN removal. T. domingensis and C. indica in HSSFWs and T. domingensis in FWSWs
      tolerated wastewater conditions. T. domingensis presented the highest
      productivity. In further research, FWSWs in series planted with T. domingensis
      should be studied.

PMID- 30199677
TI  - Loss characteristics of Cd in soil aggregates under simulated rainfall
      conditions.
AB  - Soil particles exert a significant influence on the migration of heavy metals in
      soil and water environments. In this study, a simulated rainfall experiment was
      conducted to investigate the loss characteristics of cadmium (Cd) from a red soil
      surface. Two rainfall intensities (50 and 100 mm h-1) were considered and the
      distribution of Cd in different fractions (>1, 1-0.25, 0.25-0.05 and <0.05 mm) of
      aggregates lost from the soil was examined. The result showed that in the
      artificially polluted soil, the Cd content in different aggregates decreased with
      particle size, with the lowest Cd content in the <0.05 mm fraction aggregates. In
      the rainfall experiment, the runoff rate generally increased with the rainfall
      duration, while the sediment yield rate first increased and then remained stable.
      The loss rates of various fractions of aggregates in the sediment generally
      followed the order of (<0.05) mm > 1-0.25 mm > 0.25-0.05 mm > (>1) mm. The
      proportions of the <0.05 mm-fraction aggregates were the highest in the loss
      sediment throughout the entire rainfall process. The lost Cd was transported
      mainly in the sediment-bound form, while only a very small portion of Cd was lost
      in the water phase of runoff. High rainfall intensity led to greater Cd loss in
      runoff. In the lost sediment, the concentration of Cd was higher in the
      macroaggregates. The phenomenon of Cd enrichment in the fine particles was not
      observed. Although the concentration of Cd in the <0.05 mm fraction was the
      lowest, the contribution of this fraction to the total Cd content in the
      sediments was the highest.

PMID- 30199678
TI  - Predicting cadmium concentration in soils using laboratory and field reflectance
      spectroscopy.
AB  - Visible and near-infrared spectroscopy (VNIRS, 350-2500 nm) is a promising
      alternative to rapidly investigate soil contamination by heavy metals. To explore
      the possibility of predicting heavy metal concentration in soils using laboratory
      and field reflectance spectroscopy and examine transferability of the prediction
      method, 46 soil samples from a mining area, 42 soil samples from an agricultural
      land, and the corresponding two sets of field soil spectra were collected.
      Cadmium (Cd) was taken as an example in this study. The collected soil samples
      were air-dried, ground, sieved, and then used for laboratory spectral measurement
      and chemical analysis. Soil reflectance spectroscopy associated with organic
      matter was extracted from the VNIRS and used to predict Cd concentration based on
      strong sorption and retention of Cd on soil organic matter. Genetic algorithm
      (GA) was adopted for band selection, and the selected bands were used to
      calibrate the prediction model with partial least squares regression (PLSR).
      Compared with the prediction using entire VNIR region, the ratio of prediction to
      deviation (RPD) and the coefficient of determination (R2) were improved from
      1.473 and 0.508 to 2.997 and 0.881 for laboratory spectra and 1.437 and 0.484 to
      1.992 and 0.731 for field spectra by using spectral bands associated with organic
      matter in the mining area. The RPD and R2 values were improved from 1.919 and
      0.707 to 3.727 and 0.923 for laboratory spectra and 1.057 and 0.036 to 1.747 and
      0.646 for field spectra by the prediction method in the agricultural land. The
      improvement was further revealed by prediction of Cd concentration with a
      selected subset of soil samples from the mining area. The results suggest that
      predicting Cd concentration in soils with GA-PLSR using reflectance spectroscopy
      associated with organic matter is feasible and the prediction method could have
      the potential to be applied to field conditions.

PMID- 30199679
TI  - Impervious surface area is a key predictor for urban plant diversity in a city
      undergone rapid urbanization.
AB  - Urban biodiversity has increasingly been recognized by the scientific community
      and environmental policymakers as a part of conservation efforts worldwide.
      However, most studies on urban biodiversity focus on cities in developed
      countries. An information gap exists for urban biodiversity of cities in
      developing countries. Here we focused on variability in plant diversity, a major
      component of biodiversity, in a Chinese city that has undergone rapid
      urbanization in recent time. The influence of urbanization was determined by
      comparing plant diversity and proportion of exotic/endemic plant species with the
      intensity of urbanization across the study area. We used percentage of total
      impervious surface area (PTIA) as an indicator of urbanization intensity, ranging
      from 5% to 95% across the study area. In the study area, a total of 321 plant
      species was recorded, totaling 83 trees, 113 shrubs and 125 herbs. Plant
      diversity, measured by number of plant taxa and other indices, was driven by
      PTIA; an increase in PTIA reduced plant diversity. In addition, the ratio of
      exotic to endemic plant species increased as PTIA increased. Among the exotic
      species, most of the tree and shrub species were purposely introduced. Above 40%
      PTIA, plant diversity decreased sharply and the proportion of exotic species
      rose. As a valuable predictor of urban biodiversity, PTIA can thus be used as a
      key criterion for urban planning to ameliorate urban biodiversity. Further, our
      findings extend current understanding of urban biodiversity for cities in
      developing countries.

PMID- 30199680
TI  - Microbial composition, potential functional roles and genetic novelty in gypsum
      rich and hypersaline soils of Monegros and Gallocanta (Spain).
AB  - Soil microbial communities (both Bacteria and Archaea) were studied after 16S
      rRNA genes massive sequencing in two hypersaline and gypsum-rich contrasted sites
      located in NE Spain. Soil microbial communities were also locally analysed
      according to environmental variables, including geological, physico-chemical,
      biogeochemically, and climatic data. Typical soil characteristics, climate data,
      and plant composition clearly split the two sites and major differences among the
      microbial communities for the areas were initially expected. Overall, high values
      of microbial species richness (up to 2300 taxa) and ecological diversity was
      detected in both sites. High genetic novelty levels were found mostly to
      environmental sequences, highlighting the high potential for microbiological
      studies. In contrast to the initial expectations, a substantial overlapping
      between Monegros and Gallocanta microbes was observed, indicating a high
      similarity despite of the geographical, botanical and environmental distances
      between sites, in agreement with both high dispersal and local selection inherent
      to the microbial world. The potential biogeochemical cycling showed small
      differences between sites, with presence of photosynthetic green and purple
      sulfur bacteria, cyanobacteria and aerobic and anaerobic chemolitotrophs.
      Potential for aerobic methane oxidation and anaerobic methanogenesis was observed
      in both sites, with predominance of potential nitrification mostly by ammonia
      oxidizing archaea, nitrite oxidation and denitrification, and minor contribution
      for nitrate reduction and nitrate ammonification. The predicted functions based
      on the taxonomic composition showed high overlapping between the two studied
      regions, despite their difference in gypsum richness.

PMID- 30199681
TI  - Spatial and temporal influence of onsite wastewater treatment systems,
      centralized effluent discharge, and tides on aquatic hazards of nutrients,
      indicator bacteria, and pharmaceuticals in a coastal bayou.
AB  - In the rapidly urbanizing watersheds and estuaries flowing to the Gulf of Mexico
      in Texas, USA, instream flows are increasingly influenced by point source and
      nonpoint source discharges. Spatial and temporal tidal influences on water
      quality, especially for contaminants of emerging concern (CECs), is poorly
      understood in estuaries and coastal systems. We selected Dickinson Bayou, an
      urban estuary in Galveston County, Texas, for study because it has historically
      impaired water quality, receives point source discharge from one major wastewater
      treatment plant (WWTP), while also being influenced by high densities of onsite
      sewage facilities upstream in the watershed. We explored the occurrence and
      potential hazards of aquatic contaminants, including nutrients, indicator
      bacteria for pathogens, and CECs, in relation to this point source discharge,
      across seasons and at high and low tides. Aquatic contaminants and associated
      hazards varied significantly in relation to the WWTP discharge, and were
      influenced by onsite systems. In fact, spatiotemporal water quality varied by
      class of contaminants (e.g., nutrients, indicator bacteria, CECs), which
      indicates that traditional surface water monitoring activities should account for
      such environmental complexity. This study provides a diagnostic approach for
      future studies of emerging water quality challenges across gradients of rapidly
      urbanizing coastal bays and estuaries.

PMID- 30199682
TI  - Hydrological response of Chamelia watershed in Mahakali Basin to climate change.
AB  - Chamelia (catchment area = 1603 km2), a tributary of Mahakali, is a snow-fed
      watershed in Western Nepal. The watershed has 14 hydropower projects at various
      stages of development. This study simulated the current and future hydrological
      system of Chamelia using the Soil and Water Assessment Tool (SWAT). The model was
      calibrated for 2001-2007; validated for 2008-2013; and then applied to assess
      streamflow response to projected future climate scenarios. Multi-site calibration
      ensures that the model is capable of reproducing hydrological heterogeneity
      within the watershed. Current water balance above the Q120 hydrological station
      in the forms of precipitation, actual evapotranspiration (AET), and net water
      yield are 2469 mm, 381 mm and 1946 mm, respectively. Outputs of five Regional
      Climate Models (RCMs) under two representative concentration pathways (RCPs) for
      three future periods were considered for assessing climate change impacts. An
      ensemble of bias-corrected RCM projections showed that maximum temperature under
      RCP4.5 (RCP8.5) scenario for near-, mid-, and far-futures is projected to
      increase from the baseline by 0.9  degrees C (1.1  degrees C), 1.4  degrees C
      (2.1  degrees C), and 1.6  degrees C (3.4  degrees C), respectively. Minimum
      temperature for the same scenarios and future periods are projected to increase
      by 0.9  degrees C (1.2  degrees C), 1.6  degrees C (2.5  degrees C), and 2.0 
      degrees C (3.9  degrees C), respectively. Average annual precipitation under
      RCP4.5 (RCP8.5) scenario for near-, mid-, and far-futures are projected to
      increase by 10% (11%), 10% (15%), and 13% (15%), respectively. Based on the five
      RCMs considered, there is a high consensus for increase in temperature but higher
      uncertainty with respect to precipitations. Under these projected changes,
      average annual streamflow was simulated to increase gradually from the near to
      far future under both RCPs; for instance, by 8.2% in near-, 12.2% in mid-, and
      15.0% in far-future under RCP4.5 scenarios. The results are useful for planning
      water infrastructure projects, in Chamelia and throughout the Mahakali basin, to
      ensure long-term sustainability under climate change.

PMID- 30199683
TI  - Environmental parameters, and not phylogeny, determine the composition of
      extracellular polymeric substances in microbial mats from extreme environments.
AB  - The ability to establish biofilms is a key trait for microorganisms growing in
      extreme environments. The extracellular polymeric substances (EPS) present in
      biofilms provide not only surface attachment, but also protection against all
      kinds of environmental stressors, including desiccation, salinity, temperature or
      heavy metal pollution. The acquisition of suitable biofilm characteristics might
      thus be an important process mediating the adaptation of microorganisms to novel
      environmental conditions. In this work we have characterized the EPS of 20
      phylogenetically diverse biofilms collected in situ from five contrasting extreme
      environments, including two geothermal areas (Copahue, Argentina; Seltun,
      Iceland), two cold areas (Pastoruri glacier, Peru; Byers Peninsula, Antarctica)
      and one extremely acidic river (Rio Tinto, Spain). Biofilms were subjected to
      biochemical characterization, glycan profiling and immunoprofiling with an
      antibody microarray. Our results showed that environmental conditions strongly
      influence biofilm characteristics, with microorganisms from the same environment
      achieving similar EPS compositions regardless of the phylogeny of their main
      species. The concentration of some monosaccharides in the EPS could be related to
      environmental conditions such as temperature or heavy metal toxicity, suggesting
      that in some cases stress resistance can be mediated by specific sugars. Overall,
      our results highlight the existence of conserved EPS compositional patterns for
      each extreme environment, which could in turn be exploited to engineer ecological
      adaptations in genetically modified microorganisms.

PMID- 30199684
TI  - Conjunctive use of in situ gas sampling and chromatography with geospatial
      analysis to estimate greenhouse gas emissions of a large Amazonian hydroelectric
      reservoir.
AB  - Hydroelectric power reservoirs are considered potential contributors to the
      greenhouse effect in the atmosphere through the emittance of methane and carbon
      dioxide. We combined in situ sampling and gas chromatography with geostatistical
      and remote sensing approaches to estimate greenhouse gas (GHG) emissions of a
      large hydropower reservoir. We used remote sensing data to estimate the water
      surface and geospatial interpolation to calculate total emissions as a function
      of reservoir surface area. The CH4 and CO2 gas concentrations were linearly
      correlated to sampling time, confirming the adequacy of the in situ sampling
      method to measure GHG diffusive fluxes from reservoir water surfaces. The
      combination of high purity (99.99%) ISO-norm gas standards with a gas
      chromatograph, enabled us to achieve low measurement detection limits of 0.16 and
      0.60 MUmol mol-1, respectively, for CH4 (using a flame ionization or FID
      detector) and CO2 (using a thermal conductivity or TCD detector). Our results
      show that CO2 emissions are significantly (an order of 5.102-103) higher than
      those of CH4 in both the spatial and temporal domain for this reservoir. The
      total diffusive GHG emissions over a year (June 2011 to May 2012) of the Tucurui
      hydropower reservoir being in operation, in units of tons of carbon, added up to
      6.82 * 103 for CH4 and 1.19 * 106 for CO2. We show that in situ GHG sampling
      using small floating gas chambers and high precision gas chromatography can be
      combined with geospatial interpolation techniques and remote sensing data to
      obtain estimates of diffusive GHG emissions from large water bodies with
      fluctuating water surfaces such as hydropower reservoirs. We recommend that more
      measurements and observations on these emissions are pursued in order to support
      and better quantify the ongoing discussions on estimates and mitigation of GHG
      emissions from reservoirs in the Amazon region and elsewhere in the world.

PMID- 30199685
TI  - Cu and Co nanoparticles co-doped MIL-101 as a novel adsorbent for efficient
      removal of tetracycline from aqueous solutions.
AB  - Chromium metal-organic framework (MIL-101(Cr)) has been widely studied for
      removing organic contaminants from aqueous solutions due to its excellent water
      stability and giant pore size, but its low adsorption capacity limits the
      application. In this study, a new adsorbent MIL-101 loaded with CuCo bimetallic
      nanoparticles (CuCo/MIL-101) was successfully fabricated and applied in removal
      of tetracycline (TC) from aqueous solutions. The adsorption capacity of CuCo/MIL
      101 for TC increased by 140% compared with that of pure MIL-101, which may be
      attributed to the chemical bonding between Cu and Co BNPs in MIL-101 and TC
      molecules. The effects of pH, ionic strength, humic acid and contact time on the
      adsorption were also discussed in detail. The results showed that the removal
      efficiency of TC solution with high concentration (100 mg L-1) by CuCo/MIL-101
      was still as high as 82.9%. The data of adsorption kinetics and isotherms could
      be well fitted by Elovich model and Freundlich model, respectively. According to
      the fitting parameters, the maximum adsorption capacity of CuCo/MIL-101 reached
      up to 225.179 mg g-1. Additionally, the adsorption process of TC onto CuCo/MIL
      101 was spontaneous and endothermic. Electrostatic interactions could play an
      important role in the adsorption process. The enhanced adsorption capacity,
      excellent reusability and water stability demonstrated the potential of CuCo/MIL
      101 composite as a novel adsorbent for the removal of TC from aqueous solutions.

PMID- 30199686
TI  - Chromium(VI) removal by mechanochemically sulfidated zero valent iron and its
      effect on dechlorination of trichloroethene as a co-contaminant.
AB  - Mechanochemically sulfidated microscale zero valent iron (S-mZVIbm) is a
      promising groundwater remediation material as it has been proven to be not only
      efficient in dechlorinating chlorinated compounds but also amenable to up
      scaling. Yet, its efficiency in treating metal contaminants remains barely
      studied. In this study, we investigated the mechanism and efficiencies of Cr(VI)
      removal by S-mZVIbm and its effect on TCE dechlorination as a co-contaminant. The
      Cr(VI) removal by S-mZVIbm was mainly a chemisorption process and its kinetics
      was well fitted by a pseudo-second-order model. Alkaline pH inhibited Cr(VI)
      removal while dissolved oxygen slightly depressed the Cr(VI) removal. The Cr(VI)
      removal rapidly formed a non-conductive layer on S-mZVIbm surface to hinder
      further electron transfer from Fe0 core before H+ was able to accept any
      electrons to produce H2, which resulted in 100% electron efficiencies of Cr(VI)
      removal but <1% of Fe0 utilization efficiency. The presence of Cr(VI) also
      dramatically inhibited the dechlorination of TCE and its electron efficiency as a
      co-contaminant by passivating the FeS surface. Therefore, Cr(VI) is likely to be
      an electron sink if present for remediation of other contaminants in groundwater.

PMID- 30199687
TI  - Estimating urban residential building-related energy consumption and energy
      intensity in China based on improved building stock turnover model.
AB  - Accurate estimation of urban residential building-related energy consumption
      (URBEC) and energy intensity per unit floor area at the national level has
      significant implications for the analysis of carbon emission peaks. However,
      reliable data on China's building floor space (BFS) are lacking, resulting in
      unclear energy intensity levels. This study proposes a China BFS estimation
      method (CBFSEM) based on improved building stock turnover model. Using CBFSEM, it
      estimates the BFS of historic urban dwelling stock, the demolished and newly
      built dwelling from 2000 to 2015. It then estimates the corresponding energy
      consumption and intensity based on the obtained urban residential BFS data.
      Results showed that total URBEC in China increased dramatically from 217.1 Mtce
      in 2000 to 417.2 Mtce in 2015 with an average annual growth rate of 4.45%.
      China's total dwelling stock almost doubled, from 10.6 billion m2 in 2000 to 27.4
      billion m2 in 2015 with an annual growth rate of 6.56%. The operational energy
      consumption accounted for approximately 70% of total URBEC and the building
      material production energy intensity was the highest in total URBEC, >60 kgce/m2.
      A comparison with the China Population Census showed that the deviations were
      well below 8%, which indicated the reliability of the CBFSEM and the estimated
      results. In general, this study fills the gap in available data and addresses the
      shortage of estimation methods for BFS and energy intensity. It also provides the
      government with technical support and scientific evidence to promote building
      energy efficiency.

PMID- 30199688
TI  - Management of headwaters based on macroinvertebrate assemblages and environmental
      attributes.
AB  - The ecosystem function of headwaters is important and increasingly well
      recognized, but institutional structures to administer their protection and
      management are lacking or poorly developed. Although the reasons for this
      mismatch are various, one of practical concern is the potential administrative
      burden imposed by the sizable number of headwaters. Two essential components of
      an administrative framework for managing waters is classification by type so that
      proper expectations can be set, and development of indicators that measure
      whether those expectations are being met. Ordinations of macroinvertebrate
      assemblages sampled from 1016 sites in 934 headwater streams draining <13 km2
      across Ohio, USA, revealed a highly distinct subset of sites characterized by a
      combination of taxa having an affinity for cold water and sensitivity to
      environmental disturbance. Bayesian Network (BN) modeling revealed that several
      environmental variables, notably water temperature, percent forest cover, and
      drainage area predict membership in this subset. More generally across all
      streams, macroinvertebrate assemblages signaled ecological status along a
      stressor gradient defined by habitat quality and intensity of land uses.
      Collectively, these results suggest a hierarchical administrative framework
      wherein stream habitat quality, as measured by summary habitat index scores, can
      screen and assign protections to waters generally expected to support assemblages
      consistent with good ecological status. Forest cover and water temperature can
      serve as an additional screen to assign higher levels of protection consistent
      with higher ecological status. In cases where levels of protection based on
      screening are questioned or likely to be contentious, assessment of the
      macroinvertebrate assemblage can demonstrate the appropriate level.

PMID- 30199689
TI  - Modelling the vertical gradient of nitrogen dioxide in an urban area.
AB  - INTRODUCTION: Land use regression models environmental predictors to estimate
      ground-floor air pollution concentration surfaces of a study area. While many
      cities are expanding vertically, such models typically ignore the vertical
      dimension. METHODS: We took integrated measurements of NO2 at up to three
      different floors on the facades of 25 buildings in the mid-sized European city of
      Basel, Switzerland. We quantified the decrease in NO2 concentration with
      increasing height at each facade over two 14-day periods in different seasons.
      Using predictors of traffic load, population density and street configuration, we
      built conventional land use regression (LUR) models which predicted ground floor
      concentrations. We further evaluated which predictors best explained the vertical
      decay rate. Ultimately, we combined ground floor and decay models to explain the
      measured concentrations at all heights. RESULTS: We found a clear decrease in
      mean nitrogen dioxide concentrations between measurements at ground level and
      those at higher floors for both seasons. The median concentration decrease was
      8.1% at 10 m above street level in winter and 10.4% in summer. The decrease with
      height was sharper at buildings where high concentrations were measured on the
      ground and in canyon-like street configurations. While the conventional ground
      floor model was able to explain ground floor concentrations with a model R2 of
      0.84 (RMSE 4.1 MUg/m3), it predicted measured concentrations at all heights with
      an R2 of 0.79 (RMSE 4.5 MUg/m3), systematically overpredicting concentrations at
      higher floors. The LUR model considering vertical decay was able to predict
      ground floor and higher floor concentrations with a model R2 of 0.84 (RMSE 3.8
      MUg/m3) and without systematic bias. DISCUSSION: Height above the ground is a
      relevant determinant of outdoor residential exposure, even in medium-sized
      European cities without much high-rise. It is likely that conventional LUR models
      overestimate exposure for residences at higher floors near major roads. This
      overestimation can be minimized by considering decay with height.

PMID- 30199690
TI  - Vegetation-Rainfall interactions reveal how climate variability and climate
      change alter spatial patterns of wildland fire probability on Big Island, Hawaii.
AB  - The area burned annually by wildland fire in Hawaii has increased fourfold in
      recent decades. The archipelago's novel fuel types and climatic heterogeneity
      pose significant challenges for fire risk assessment and fire management.
      Probability-based fire occurrence models using historical wildfire records
      provide a means to assess and attribute fire risk in regions of the world like
      Hawaii where investment in fire science is limited. This research used
      generalized additive models to 1) assess the relative contribution of vegetation,
      climate, and human-caused ignitions to the probability of fire in the northwest
      quadrant of Hawaii Island and 2) compare how landscape flammability varies due to
      interannual rainfall variability versus projected changes in mean annual rainfall
      (MAR) and temperature. Annual fire probability was highest for grasslands and
      peaked at drier conditions (0.04 at 450 mm MAR) when compared with shrublands
      (0.03 at 650 mm MAR) and forest (0.015 at 600 mm MAR). Excess rainfall the year
      prior to fire occurrence increased fire risk across grasslands, and thus overall
      fire probability, more so than drought the year that fire occurred. Drying and
      warming trends for the region under projected climate change increased maximum
      values of fire probability by as much as 375% and shifted areas of peak landscape
      flammability to higher elevation. Model predictions under future climate also
      indicate the largest changes in landscape flammability will happen by mid
      Century. The influence of antecedent wet years on fire risk can improve near-term
      predictions of fire risk in Hawaii while climate projections indicate that fire
      management will need to be prioritized at upper elevations where high value
      natural resources are concentrated.

PMID- 30199691
TI  - Variations in hydrogen isotopic fractionation in higher plants and sediments
      across different latitudes: Implications for paleohydrological reconstruction.
AB  - Sedimentary deltaDn-alkane value is widely utilized as a reliable proxy for paleo
      hydrological reconstruction. Applications of this proxy must be based upon a
      globally clear understanding of the relationship between leaf wax deltaDn-alkane
      values and precipitation deltaD (deltaDp), defined as apparent fractionation
      (epsilonapp). However, there is a critical concern about whether relatively
      constant epsilonapp values exist across different latitudes. In this study, we
      systematically analyzed the variations of available epsilonapp with latitudes
      based upon two compiled-new databases of higher plants and sediments over the
      world. We found that the total average epsilonapp was relatively constant, i.e., 
      116 +/- 50/00 (n = 941), in higher plants across different latitudes without
      consideration of plant types (e.g., dicots, monocots, gymnosperms), and was still
      constant but slightly lower average epsilonapp, i.e., -125 +/- 60/00 (n = 460),
      in sediments across the latitudes. The slightly lower average epsilonapp in
      sediments relative to higher plants probably derived from the contribution of
      aquatic plants with isotopically D-depleted epsilonapp in lake sediments.
      Interestingly, with consideration of plant types, average epsilonapp increased in
      dicots but decreased in monocots slightly from low to high latitudes. The
      counteraction of these competing trends generates relatively constant average
      epsilonapp values in higher plants, and resultantly constant average epsilonapp
      values occur in sediments at the global scale. It is important to elaborate
      relatively constant epsilonapp values from higher plants and sediments across
      different latitudes when sedimentary deltaDn-alkane is utilized as a proxy for
      paleohydrological reconstruction.

PMID- 30199692
TI  - Transient analytical solution for one-dimensional transport of organic
      contaminants through GM/GCL/SL composite liner.
AB  - Analytical solution for transport of organic contaminants through composite liner
      consisting of a geomembrane (GM), a geosynthetic clay liner (GCL), and a soil
      liner (SL) with finite thickness is presented. The transient diffusion-advection
      processes in the whole composite liner and adsorption in GCL and SL can be
      described by the present method. The method is successfully verified against
      analytical solution to a coupling transient diffusion-advection problem in double
      layer porous media. The rationality of the steady-state transport assumption in
      GM and GCL and the semi-infinite bottom boundary assumption, which are widely
      adopted in the existing works, is comprehensively investigated. The overestimated
      zone, underestimated zone and no difference zone caused by the two assumptions
      under various conditions are identified. With the increase of elapsed time, the
      overestimated zone disappears, and the underestimated zone becomes smaller and
      smaller and finally is overwhelmed by the no difference zone. Moreover, the
      equivalency between GM/GCL/SL and GM/CCL composite liners is also properly
      assessed by the present method. GM/GCL/SL composite liner performs better than
      GM/CCL composite liner under high leachate level condition.

PMID- 30199693
TI  - Disentangling the effects of spatial proximity and genetic similarity on
      individual growth performances in Norway spruce natural populations.
AB  - Cambial growth is a phenotypic trait influenced by various physiological
      processes, numerous biotic and abiotic drivers, as well as by the genetic
      background. By archiving the outcome of such complex interplay, tree-rings are an
      exceptional resource for addressing individual long-term growth responses to
      changing environments and climate. Disentangling the effects of the different
      drivers of tree growth, however, remains challenging because of the lack of
      multidisciplinary data. Here, we combine individual dendrochronological, genetic
      and spatial data to assess the relative importance of genetic similarity and
      spatial proximity on Norway spruce (Picea abies (L.) Karst.) growth performances.
      We intensively sampled five plots from two populations in southern and central
      Europe, characterizing a total of 482 trees. A two-step analytical framework was
      developed. First, the effects of climate and tree age on tree-ring width (TRW)
      were estimated for each individual using a random slope linear mixed-effects
      model. Individual parameters were then tested against genetic and spatial
      variables by Mantel tests, partial redundancy analyses and variance partitioning.
      Our modelling approach successfully captured a large fraction of variance in TRW
      (conditional R2 values up to 0.94) which was largely embedded in inter-individual
      differences. All statistical approaches consistently showed that genetic
      similarity was not related to variation in the individual parameters describing
      growth responses. In contrast, up to 29% of the variance of individual parameters
      was accounted by spatial variables, revealing that microenvironmental features
      are more relevant than genetic similarity in determining similar growth patterns.
      Our study highlights both the advantages of modelling dendrochronological data at
      the individual level and the relevance of microenvironmental variation on
      individual growth patterns. These two aspects should be carefully considered in
      future multidisciplinary studies on growth dynamics in natural populations.

PMID- 30199694
TI  - Psychometric properties and cross-cultural comparison of the cognitive complaints
      in bipolar disorder rating assessment (COBRA) in Mexican patients with bipolar
      disorder.
AB  - Bipolar Disorder (BD) is a serious and frequent mental health condition that is
      sometimes fatal. Several longitudinal studies have found an important correlation
      between cognition and functionality in BD. Despite the known importance of
      cognitive symptoms in BD, evaluation of cognitive deficits is not routinely done
      in clinical settings, as assessment is time-consuming and requires
      neuropsychological testing. The aim was to evaluate the psychometric properties
      of the subjective cognitive deficits in bipolar disorder (COBRA) rating scale in
      a Mexican sample of patients with BD and perform a cross-cultural comparison with
      the results obtained in other cultures. Ninety-two Healthy Subjects and 80
      euthymic patients with BD were asked to complete the COBRA rating scale. The
      psychometric properties found in Mexican population show a good internal
      consistency and good discriminant validity with control subjects. Adequate
      congruence coefficients were obtained between the COBRA analyses in Mexican
      population and Spanish population and acceptable when compared to Japanese
      population. The COBRA scale is a brief and valid measure of cognitive complaints
      in BD for use in Mexican population.

PMID- 30199695
TI  - Suicidal ideation and attempts in patients who seek treatment for substance use
      disorder.
AB  - Patients with substance dependence have a great risk of suicidal ideation and
      attempts. The study of the specific risk characteristics of patients with
      substance use disorders who present with suicidal ideation and/or attempts
      becomes a crucial clinical issue in order to develop prevention strategies. The
      main goals of this study were to determine the prevalence rate of both suicidal
      ideation and attempts among patients receiving treatment for substance use
      disorder and to analyse the differential characteristics between these patients
      with and without suicidal behaviours. A sample of 334 patients (263 men-71 women)
      who sought treatment for substance use disorder in a Spanish clinical centre was
      assessed. In total, 43.7% of the patients presented with lifetime suicidal
      ideation (8.7% in the last month) and 17.7% with suicide attempts (1.5% in the
      last month). Patients with suicidal ideation or attempts showed a more severe
      addiction profile (assessed by the EuropASI), and more psychopathological
      symptoms (assessed by the SCL-90-R). Moreover the rate of suicidal ideation and
      attempts was significantly higher in inpatients than in outpatients. According to
      these results, systematic screening of suicidal risk in patients seeking
      treatment for substance use disorders is recommended, especially in those with a
      greater addiction severity.

PMID- 30199697
TI  - A comparative study of the typical toxic metals in serum by patients of
      schizophrenia and healthy controls in China.
AB  - Toxic metals are ubiquitous environmental pollutants, and their potential risks
      associated with the development of schizophrenia remain a subject of debate. In
      this study, we investigated the associations between six typical toxic metals
      (mercury, lead, chromium, silver, antimony, and uranium) in serum with the risk
      of schizophrenia using a case-control study design. In total, 109 patients with
      schizophrenia (cases) and 106 normal subjects (controls) from Shandong Province,
      China were recruited. Fasting blood samples were collected from all participants,
      as well as serum samples from the cases before and after medical treatment. The
      six metals were analyzed by inductively coupled plasma mass spectrometry. Only
      three metals (antimony, silver and uranium) had acceptable detection rates of
      >80%. The concentrations of antimony and uranium were significantly higher in the
      cases than in the controls, while no significant difference for silver. Moreover,
      the serum concentrations of antimony and uranium were significantly lower after
      medical treatment. Clear dose-response relationships between serum metal
      concentrations and the risk of schizophrenia were observed, even after adjusting
      for potential covariates. This suggests that higher levels of antimony and
      uranium may be one of the factors associated with an elevated risk of
      schizophrenia.

PMID- 30199698
TI  - Retirement and depressive symptoms: A 10-year cross-lagged analysis.
AB  - The effect of retirement on depressive symptoms remains a subject of scientific
      inquiry, given the fact that previous studies have found mixed results. Moreover,
      the possible effect of depressive symptoms on the propensity to retire remains
      relatively understudied. Given the sheer number of retirees, and the significance
      of depressive symptoms for individuals' well-being and ability to work, as well
      as for societies at large, we used a large longitudinal dataset to examine the
      reciprocal effects of retirement on depressive symptoms, and of depressive
      symptoms on the propensity to retire. Using six waves of the Health and
      Retirement Study (HRS) data collected over a period of 10 years (N = 6584), we
      tested cross-lagged models of the reciprocal relationships between retirement and
      depressive symptoms. The analysis revealed that retirement results in increased
      depressive symptoms, and that depressive symptoms increase the likelihood of
      retirement. No sex differences in the lagged associations were found. We conclude
      that depressive symptoms are a risk factor for retirement, and practitioners
      should try and identify older workers suffering from depression prior to the
      retirement transition. Similarly, as retirement increases depressive symptoms,
      the transition should be treated as an important and sometimes risky milestone,
      where adequate preparation is required.

PMID- 30199699
TI  - Negative association between BMI and depressive symptoms in middle aged and
      elderly Chinese: Results from a national household survey.
AB  - The association between body size and mental health has been the focus of many
      studies. Results, however, varies between studies. This study aimed to
      investigate the association between BMI and depressive symptoms among Chinese
      adults. We also further explored childhood starvation as a potential mediator of
      this association. The China Health and Retirement Longitudinal Study data, a
      representative national survey of adults age 45 and older was used in this study.
      Results showed that the prevalence of overweight and obesity were 28.8% and
      11.6%. There was a negative association between BMI and depressive symptoms for
      males. Obese male adults had the lowest CES-D scores, followed by overweight male
      adults, and underweight male adults had the highest CES-D scores. These
      associations also exist but are not significant for females. Furthermore, these
      associations were significant among males who had been exposed to food shortage
      during their childhood. Our results suggested a significant positive association
      between BMI and depression in middle aged and elderly males in China, while this
      association is weak in females. Childhood food shortage experience was a
      potential causative factor accounting for this association.

PMID- 30199696
TI  - Refinement of anxiety sensitivity measurement: The Short Scale Anxiety
      Sensitivity Index (SSASI).
AB  - Anxiety sensitivity, defined as the fear of anxiety and arousal-related
      sensations, has been among the most influential cognitive-based transdiagnostic
      risk and maintenance factors in the study and treatment of emotional and related
      disorders. The currently available anxiety sensitivity measures are limited by
      their length. Specifically, the length of these instruments discourages the
      adoption of routine anxiety sensitivity assessment in clinical or medical
      settings (e.g., primary care). The goals of this study were to develop and assess
      the validity and reliability of a short version of the Anxiety Sensitivity Index
      3 (ASI-3; Taylor et al., 2007), entitled the Short Scale Anxiety Sensitivity
      Index (SSASI), using three independent clinical samples. Results indicated that
      the abbreviated five-item version of the SSASI had good internal consistency and
      a robust association with the ASI-3. Further, across the samples, there was
      evidence of unidimensionality and excellent convergent and discriminant validity.
      There also was evidence of partial measurement invariance across sex and full
      measurement invariance across time. Overall, the five-item scale offers a single
      score that can be employed to measure anxiety sensitivity. Use of the SSASI may
      facilitate screening efforts and symptom tracking for anxiety sensitivity,
      particularly within clinical settings where practical demands necessitate the use
      of brief assessment instruments.

PMID- 30199701
TI  - Anode modification by biogenic gold nanoparticles for the improved performance of
      microbial fuel cells and microbial community shift.
AB  - In this study, carbon cloth anodes were modified using biogenic gold
      nanoparticles (BioAu) and nanohybrids of multi-walled carbon nanotubes blended
      with BioAu (BioAu/MWCNT) to improve the performance of microbial fuel cells
      (MFCs). The results demonstrated that BioAu modification significantly enhanced
      the electricity generation of MFCs. In particular, BioAu/MWCNT nanohybrids as the
      modifier displayed a better performance. The MFC with the BioAu/MWCNT electrode
      had the shortest start-up time (6.74 d) and highest power density (178.34 +/-
      4.79 mW/m2), which were 141.69% shorter and 56.11% higher compared with those of
      the unmodified control, respectively. These improvements were attributed to the
      excellent electrocatalytic activity and strong affinity towards exoelectrogens of
      the BioAu/MWCNT nanohybrids on the electrode. High throughput sequencing analysis
      indicated that the relative abundance of electroactive bacteria in the biofilm
      community, mostly from the classes of Gammaproteobacteria and Negativicutes,
      increased after anode modification.

PMID- 30199700
TI  - Application of microbial fuel cell technology for wastewater treatment and
      electricity generation under Nordic countries climate conditions: Study of
      performance and microbial communities.
AB  - Two microbial fuel cells were inoculated with activated sludge from Finland and
      operated under moderate (25  degrees C) and low (8  degrees C) temperatures.
      Operation under real urban wastewater showed similarities in chemical oxygen
      demand removal and voltage generated, although moderate temperature supported
      higher ammonium oxidation. Fungi disappeared in the microbial fuel cell operated
      at temperature of 25  degrees C. Archaea domain was dominated by methanogenic
      archaea at both temperature scenarios. Important differences were observed in
      bacterial communities between both temperatures, however generating similar
      voltage. The results supported that the implementation of microbial fuel cells in
      Nordic countries operating under real conditions could be successful, as well as
      suggested the flexibility of cold-adapted inoculum for starting-up microbial fuel
      cells, regardless of the operating temperature of the system, obtaining higher
      COD removal and voltage generation performances at low temperature than at
      moderate temperature.

PMID- 30199702
TI  - A beta-glucuronidase-responsive albumin-binding prodrug for potential selective
      kinase inhibitor-based cancer chemotherapy.
AB  - We report on the synthesis and in vitro biological evaluations of a nanomolar
      protein kinase inhibitor (PKI) and its beta-glucuronidase-responsive albumin
      binding prodrug. The highly potent PKI is 400-3400 times more cytotoxic than the
      well-known PKI Roscovitine. The prodrug is able to bind covalently to human serum
      albumin through Michael addition and release the cytotoxic PKI in the presence of
      beta-glucuronidase, an enzyme over-expressed in the microenvironment of solid
      tumours.

PMID- 30199703
TI  - The synthesis and kinetic evaluation of aryl alpha-aminophosphonates as novel
      inhibitors of T. cruzi trans-sialidase.
AB  - The trans-sialidase protein expressed by Trypanosoma cruzi is an important enzyme
      in the life cycle of this human pathogenic parasite and is considered a promising
      target for the development of new drug treatments against Chagas' disease. Here
      we describe alpha-amino phosphonates as a novel class of inhibitor of T. cruzi
      trans-sialidase. Molecular modelling studies were initially used to predict the
      active-site binding affinities for a series of amino phosphonates, which were
      subsequently synthesised and their IC50s determined in vitro. The measured
      inhibitory activities show some correlation with the predictions from molecular
      modelling, with 1-napthyl derivatives found to be the most potent inhibitors
      having IC50s in the low micromolar range. Interestingly, kinetic analysis of the
      mode of inhibition demonstrated that the alpha-aminophosphonates tested here
      operate in a non-competitive manner.

PMID- 30199704
TI  - Design, synthesis and identification of novel substituted 2-amino thiazole
      analogues as potential anti-inflammatory agents targeting 5-lipoxygenase.
AB  - Human 5-Lipoxygenase (5-LOX) is a key enzyme targeted for asthma and
      inflammation. Zileuton, the only drug against 5-LOX, was withdrawn from the
      market due to several problems. In the present study, the performance of
      rationally designed conjugates of thiazole (2) and thiourea (3) scaffolds from
      our previously reported 2-amino-4-aryl thiazole (1) is reported. They are
      synthesized (total 31 derivatives), characterized, and tested against the 5-LOX
      enzyme in vitro and the mode of action of the most active ones are determined.
      Compound 2m exhibited an IC50 of 0.9 +/- 0.1 MUM acting through competitive (non
      redox) mechanism, unlike Zileuton, and found to be devoid of radical scavenging
      properties. Computational studies are in good agreement with the experimental
      data supporting its mechanism of action. Another lead molecule from the thiourea
      series (3), 3f, exhibited an IC50 of 1.4 +/- 0.1 MUM against 5-LOX whose mode of
      action is redox type (non-competitive). It is promising to note that the
      activities displayed by both the lead inhibitors, 2m and 3f, are better than the
      commercial drug, Zileuton (IC50 = 1.5 +/- 0.3 MUM). These inhibitors could be
      further developed as drugs against inflammation.

PMID- 30199705
TI  - Structure-activity relationship study of hypoxia-activated prodrugs for
      proteoglycan-targeted chemotherapy in chondrosarcoma.
AB  - Due to an abundant chondrogenic, poorly vascularized and particularly hypoxic
      extracellular matrix, chondrosarcoma, a malignant cartilaginous tumour, is chemo-
      and radio-resistant. Surgical resection with wide margins remains the mainstay of
      treatment. To address the lack of therapy, our strategy aims to increase
      anticancer drugs targeting and delivery in the tumour, by leveraging specific
      chondrosarcoma hallmarks: an extensive cartilaginous extracellular matrix, namely
      the high negative fixed charge density and severe chronic hypoxia. A dual
      targeted therapy for chondrosarcoma was investigated by conjugation of a hypoxia
      activated prodrug (HAP) to quaternary ammonium (QA) functions which exhibit a
      high affinity for polyanionic sites of proteoglycans (PGs), the major components
      of the chondrosarcoma extracellular matrix. Based on preclinical results, an
      imidazole prodrug, ICF05016, was identified and provided the basis for a lead
      optimization study. A series of 27 QA-phosphoramide mustard conjugates, differing
      by the type of QA function and the length of the alkyl linker, was yielded by a
      common multi-step sequence involving phosphorylation of a key 2-nitroimidazole
      alcohol. Then, a screening was realized by surface plasmon resonance technology
      to assess biomolecular interactions between QA derivatives and aggrecan, the most
      abundant PG in chondrosarcoma. Results revealed that affinity depends more on the
      type of QA function, than on the linker length. Moreover, the presence of a
      benzyl group enhanced affinity to aggrecan. Twelve compounds were shortlisted and
      evaluated for antiproliferative activity (i.e., growth inhibiting concentration
      50), under normoxic and hypoxic conditions using the human extraskeletal myeloid
      chondrosarcoma cell line (HEMC-SS). For all prodrugs, hypoxic selectivity was
      maintained and even increased, compared with the lead. From this study, compound
      31f emerged as the most effective PG-targeted HAPs with a dissociation constant
      of 2.10 MUM in the SPR experiment, a hypoxia cytotoxicity ratio of 24 and an
      efficient reductive cleavage under chemical and enzymatic conditions.

PMID- 30199707
TI  - Role of p53 circuitry in tumorigenesis: A brief review.
AB  - Maintenance of genome integrity under the stressed condition is paramount for
      normal functioning of cells in the multicellular organisms. Cells are programmed
      to protect their genome through specialized adaptive mechanisms which will help
      decide their fate under stressed conditions. These mechanisms are the outcome of
      activation of the intricate circuitries that are regulated by the p53 master
      protein. In this paper, we provided a comprehensive review on p53, p53 homologues
      and their isoforms, including a description about the ubiquitin-proteasome system
      emphasizing its role in p53 regulation. p53 induced E3(Ub)-ligases are an
      integral part of the ubiquitin-proteasome system. This review outlines the roles
      of important E3(Ub)-ligases and their splice variants in maintaining cellular p53
      protein homeostasis. It also covers up-to-date and relevant information on small
      molecule Mdm2 inhibitors originated from different organizations. The review ends
      with a discussion on future prospects and investigation directives for the
      development of next-generation modulators as p53 therapeutics.

PMID- 30199706
TI  - Novel antimalarial chloroquine- and primaquine-quinoxaline 1,4-di-N-oxide
      hybrids: Design, synthesis, Plasmodium life cycle stage profile, and preliminary
      toxicity studies.
AB  - Emergence of drug resistance and targeting all stages of the parasite life cycle
      are currently the major challenges in antimalarial chemotherapy. Molecular
      hybridization combining two scaffolds in a single molecule is an innovative
      strategy for achieving these goals. In this work, a series of novel quinoxaline
      1,4-di-N-oxide hybrids containing either chloroquine or primaquine pharmacophores
      was designed, synthesized and tested against both chloroquine sensitive and
      multidrug resistant strains of Plasmodium falciparum. Only chloroquine-based
      compounds exhibited potent blood stage activity with compounds 4b and 4e being
      the most active and selective hybrids at this parasite stage. Based on their
      intraerythrocytic activity and selectivity or their chemical nature, seven
      hybrids were then evaluated against the liver stage of Plasmodium yoelii,
      Plasmodium berghei and Plasmodium falciparum infections. Compound 4b was the only
      chloroquine-quinoxaline 1,4-di-N-oxide hybrid with a moderate liver activity,
      whereas compound 6a and 6b were identified as the most active primaquine-based
      hybrids against exoerythrocytic stages, displaying enhanced liver activity
      against P. yoelii and P. berghei, respectively, and better SI values than
      primaquine. Although both primaquine-quinoxaline 1,4-di-N-oxide hybrids slightly
      reduced the infection of mosquitoes, they inhibited sporogony of P. berghei and
      compound 6a showed 92% blocking of transmission. In vivo liver efficacy assays
      revealed that compound 6a showed causal prophylactic activity affording
      parasitaemia reduction of up to 95% on day 4. Absence of genotoxicity and in vivo
      acute toxicity were also determined. These results suggest the approach of
      primaquine-quinoxaline 1,4-di-N-oxide hybrids as new potential dual-acting
      antimalarials for further investigation.

PMID- 30199709
TI  - In-site synthesis molecular imprinting Nb2O5 -based photoelectrochemical sensor
      for bisphenol A detection.
AB  - In this work, a photoelectrochemical (PEC) sensor based on inorganic surface
      molecular imprinting Nb2O5 (MI-Nb2O5) for detection of bisphenol A (BPA) had been
      developed. In the PEC sensor, MI-Nb2O5 material was synthesized based on an in
      situ surface molecular imprinting technique. The microstructure characteristics
      of the as-prepared photoactive materials were systematically investigated by XRD,
      SEM, TEM, XPS, FTIR and UV-vis spectroscopy. The PEC detection results showed
      that the MI-Nb2O5 material had higher photocurrent responses and excellent
      selectivity for contaminant BPA under UV-light irradiation owing to the abundant
      special recognition sites on the surface of MI-Nb2O5. Besides, the PEC sensor
      exhibited a wide detection range from 0.01 nmol.L-1 to 30 nmol.L-1 with a low
      limit of detection (LOD) of 0.004 nmol.L-1. The interferences test showed that
      the sensor had a good selectivity to BPA molecules in the different interference
      solutions. This method combining molecular imprinting technique with
      photoelectrochemical detection measurement made a successful attempt to detect
      BPA and supplied a promising way to detect other environment pollutions rapidly
      and selectively in the future.

PMID- 30199708
TI  - Design, synthesis and pharmacological evaluation of a novel PEG-cRGD-conjugated
      irinotecan derivative as potential antitumor agent.
AB  - A novel PEG-cRGD-conjugated irinotecan derivative BGC0222 was designed and
      synthesized as antitumor agent. Antitumor activity screening assay indicated that
      BGC0222 exhibited better in vitro antiproliferation activity than irinotecan and
      NKTR-102 against HT29, MIA PaCa-2 and MCF-7 tumor cell lines, with IC50 of 1.83
      +/- 0.09 MUM, 3.95 +/- 0.16 MUM and 0.68 +/- 0.04 MUM, respectively, while it
      displayed better in vivo antiproliferation activity than irinotecan and NKTR-102
      in HT-29, MIA PaCa-2, NCI-H446, U-87 MG and MDA-MB-231 xenograft models. The
      action mechanism of BGC0222 was then investigated by integrin-binding competition
      (IBC) and chick chorioallantoic membrane (CAM) angiogenesis assays, which
      indicated that BGC0222 may exert antitumor activity by binding to alphavbeta3
      target and consequently inducing neovascularization effect. Pharmacokinetic
      analysis showed that BGC0222 could slowly and steadily release irinotecan, which
      was subsequently metabolized into 7-ethyl-10-hydroxycamptothecin (SN-38) in the
      whole blood.

PMID- 30199710
TI  - TBET-based ratiometric fluorescent probe for Hg2+ with large pseudo-Stokes shift
      and emission shift in aqueous media and intracellular colorimetric imaging in
      live Hela cells.
AB  - The detection of Hg2+ in biological systems and its imaging is of highly
      importance. In this work, a novel ratiometric fluorescence probe is developed
      based on through-bond energy transfer (TBET) with a 2-(2
      hydroxyphenyl)benzoxazole (HBO) as donor and a Rhodamine derivative-Hg conjugate
      (RDM-Hg) as acceptor. Hg2+ weakens the fluorescence of HBO at 430 nm and
      meanwhile interacts with Rhodamine B derivative to form a fluorescent conjugate
      (RDM-Hg) giving rise to emission at 597 nm with a 167 nm red-shift. Further, the
      difference 282 nm between the donor absorption (315 nm) and the accepter emission
      (597 nm) for 1+Hg2+ is comparable to the highest value of the Stokes shift (282
      nm) reported earlier for other reported TBET-based cassette. Through-bond energy
      transfer from HBO to RDM-Hg is triggered by Hg2+ resulting in concentration
      dependent variation of fluorescence ratio I597/I430. A linear calibration of
      I597/I430versus Hg2+ concentration is obtained within 0-5 MUM, along with the
      lowest detection limit being found to be as low as 1.31 * 10-9 mol.L-1 (~ 0.26
      ppb) for Hg2+. This feature is further demonstrated by colorimetric imaging of
      test strip and intracellular Hg2+. On the other hand, the HBO/RDM TBET sensing
      system is characterized by a combination of high sensitivity and selectivity. The
      present study provides an approach for further development of ratiometric probes
      dedicated to selective in vitro or in vivo sensing some species of biologically
      interest.

PMID- 30199711
TI  - Electrically controlled Michael addition: Addressing of covalent immobilization
      of biological receptors.
AB  - Electrically addressed covalent immobilization of biomolecules to the defined
      electrodes of an electrode array is described. It is based on Michael addition of
      the thiol group of biomolecules to alpha,beta-unsaturated carbonyl groups of
      benzoquinone. This "click" reaction was tested by immobilization of a number of
      thiolated compounds on the simplest array consisting of two gold electrodes
      coated by a self-assembled monolayer of benzoquinone-terminated hexanethiol.
      Electrically controlled binding of hexanethiol, ferrocenylhexanethiol, human
      serum albumin and thiol-terminated single-stranded DNA (ssDNA) was investigated.
      The binding was studied using cyclic voltammetry, X-ray photoelectron
      spectroscopy and surface plasmon resonance. The reaction requires the oxidized
      state of the benzoquinone moiety; this can be reached by applying of a moderate
      anodic potential to the electrode. Surface plasmon resonance measurements
      demonstrated that the thiol-modified ssDNA immobilized by this technique binds
      complementary synthetic oligonucleotides or PCR-amplified DNA fragments. The
      developed technology of electrical addressing of covalent immobilization can be
      applied for fabrication of sensor arrays.

PMID- 30199712
TI  - Electrochemical immunosensor based on chitosan/conductive carbon black composite
      modified disposable ITO electrode: An analytical platform for p53 detection.
AB  - In this study, we fabricated a label-free electrochemical immunosensor for
      sensitive and selective detection of tumor marker p53. This immunosensor was
      based on chitosan/carbon black composite (Chitosan-CB) layer coated ITO
      electrode. This composite was utilized for enhancement of the conductivity of the
      immunosensor. Anti-p53 antibodies were captured on the modified ITO electrode
      through the cross-linking of chitosan and glutaraldehyde. Electrochemical
      impedance spectroscopy (EIS) and cyclic voltammetry (CV) techniques were utilized
      for electrochemical characterization of the proposed immunosensor. Moreover, the
      biosensor construction steps were monitored by using scanning electron microscopy
      (SEM) and atomic force microscopy (AFM). The immobilization of anti-p53
      antibodies on the electrode surface was investigated by using Fourier-transform
      infrared spectroscopy (FTIR) and Raman spectroscopy. The change in impedance
      which formed during the specific interaction between anti-p53 antibody and p53
      antigen was used to detect p53. Under optimized experimental conditions, the
      fabricated immunosensor had a wide linear range of 0.01-2 pg/mL and low detection
      limit of 3 fg/mL. The fabricated immunosensor had good sensitivity, stability and
      repeatability. Furthermore, it was successfully applied to analyze p53 in human
      serum.

PMID- 30199713
TI  - Oligonucleotide-modulated photocurrent enhancement of a tetracationic porphyrin
      for label-free homogeneous photoelectrochemical biosensing.
AB  - This work reports the first demonstration of an oligonucleotide-modulated label
      free homogeneous photoelectrochemical (PEC) biosensing platform based on the
      adsorption of tetracationic porphyrin (denoted as TMPyP here) onto 1
      naphthalenesulfonate anion (NS-)-grafted indium tin oxide electrode (denoted as
      TMPyP-NS--ITO), which generates a stable and rapid photocurrent response. We
      found that when NS--ITO electrode was subjected to single-stranded
      oligonucleotide (ssON) before TMPyP adsorption, a remarkable enhancement of
      photocurrent intensity was observed from the resulted TMPyP-ssON-NS--ITO
      electrode with high specificity towards oligonucleotide. A series of
      investigations were carried out to understand the mechanism of this
      oligonucleotide-modulated photocurrent enhancement phenomenon. Moreover, the
      studies of this robust photocurrent enhancement mechanism was successfully
      extended to develop a signal-on homogeneous PEC biosensing platform for, as a
      proof-of-concept, label-free M.SssI methyltransferase activity analysis through a
      judiciously and compatibly engineered signal transduction strategy consisted of
      hairpin-shaped oligonucleotide probe, restriction endonuclease HpaII, and
      Exonuclease I. The rationally designed homogeneous PEC biosensor exhibit
      sensitive PEC response toward M.SssI methyltransferase with a low detection limit
      of 3.5 mU/mL and a wide linear range from 0.01 to 120 U/mL. Additionally, we show
      that our homogeneous PEC biosensing platform can be also utilized to screen
      methyltransferase inhibitors. Therefore, this work will provide a distinctive
      paradigm for versatile homogeneous PEC biosensing platform that can be used as
      potential powerful tool toward innovative label-free bioanalytical purposes.

PMID- 30199714
TI  - Electrochemical sensing platform based on the biomass-derived microporous carbons
      for simultaneous determination of ascorbic acid, dopamine, and uric acid.
AB  - A novel and highly selective electrochemical sensing platform (ZnCl2-CF/GCE)
      based on combination of kiwi skin and zinc chloride nanoparticles was developed
      for the simultaneous detection of ascorbic acid (AA), dopamine (DA), and uric
      acid (UA). The constructed electrode shows a high surface area and micro
      mesoporous structure. And the electrochemical behaviors of the electrode were
      further explored by cyclic voltammetry (CV), impedance analysis (EIS), and
      differential pulse voltammetry (DPV). Under the optimal conditions, the ZnCl2-CF
      provides a high sensitivity and selective signaling in the co-existence system of
      AA, DA, and UA with linear response ranges of 0.05-200 MUM, 2-2000 MUM, and 1
      2500 MUM, respectively. The detection limits (S/N = 3) were calculated to be 0.02
      MUM, 0.16 MUM, and 0.11 MUM, respectively. In addition, the method has been
      successfully applied to determine AA, DA, and UA in real samples, which provides
      potential applications in further sensing study.

PMID- 30199715
TI  - Highly selective and sensitive ratiometric fluorescent polymer dots for detecting
      hypochlorite in 100% aqueous media.
AB  - Hypochlorite (ClO-), as a momentous reactive oxygen species (ROS), is highly
      desirable due to it associated with a number of human diseases. Therefore, the
      development of simple and convenient water-soluble ratiometric fluorescent probes
      is of great significance. In this work, water-soluble ratiometric fluorescent
      polymer dots (FPDs) for detecting ClO- were prepared via incorporation of
      reversible addition-fragmentation chain transfer radical polymerization (RAFT),
      grafting technique and coprecipitation strategy. Upon the addition of ClO-, due
      to the intramolecular heavy atom effect (HAE) by chlorine (Cl), the fluorescence
      of fluorescein units in FPDs was significantly quenched, while another reference
      fluorophore (P2) in FPDs keeps constant. Furthermore, the FPDs exhibited
      excellent sensitivity (detection limit: 2.2 nM) and selectivity, good water
      solubility. In addition, FPDs was successfully utilized to detect ClO- in tap
      water and drink water. It implies that the nanoprobes have the great potential
      applications in biological sensing and imaging.

PMID- 30199716
TI  - Resonance light scattering sensor of the metal complex nanoparticles using
      diethyl dithiocarbamate doped graphene quantum dots for highly Pb(II)-sensitive
      detection in water sample.
AB  - This study was aimed to detect Pb2+ using diethyl dithiocarbamate-doped graphene
      quantum dots (DDTC-GQDs) based pyrolysis of citric acid. The excitation maximum
      wavelength (lambdamax, ex = 337 nm) of the DDTC-GQDs solution was blue shift from
      bare GQDs (lambdamax, ex = 365 nm), with the same emission maximum wavelength
      (lambdamax, em = 459 nm) indicating differences in the desired N, S matrices
      decorating in the nanoparticles. Their resonance light scattering intensities
      were peaked at the same lambdamax, ex/em = 551/553 nm without any background
      effect of both ionic strength and masking agent. Under optimal conditions, the
      linear range was 1.0-10.0 MUg L-1 (R2 = 0.9899), limit of detection was 0.8 MUg L
      1 and limit of quantification was 1.5 MUg L-1. The precision, expressed as the
      relative standard deviations, for intra-day and inter-day analyses was 0.87% and
      4.47%, respectively. The recovery study of Pb2+ for real water samples was ranged
      between 80.8% and 109.5%. The proposed method was also proved with certified
      water sample containing 60 MUg L-1 Pb2+ giving an excellent accuracy and was then
      implied satisfactorily for ultra-trace determination of Pb2+ in drinking water
      and tap water samples.

PMID- 30199717
TI  - Maternal sensitivity is associated with configural processing of infant's cues in
      preterm and full-term mothers.
AB  - BACKGROUND: Prematurity may affect mother-infant bonding and alter maternal
      sensitivity to infant's cues. Efficient perception of infants' facial and bodily
      cues is a crucial aspect of maternal sensitivity and may be challenged by
      prematurity, as infants' signals may not be easily intelligible. However, it is
      still unexplored how premature birth impacts the maternal ability to perceive
      infants' signals. AIMS: To investigate whether prematurity influences the
      perceptual sensitivity of mothers to infants' cues and, in particular, the
      configural processing of the faces and bodies of familiar and unfamiliar infants.
      STUDY DESIGN: The inversion effect paradigm was used to evaluate the configural
      vs. detail-based processing of the face and body of own or others' infants.
      Preterm mothers were compared to full-term mothers with either low or high
      maternal sensitivity. PARTICIPANTS: Forty-three healthy full-term and twenty-one
      preterm mothers of infants aged about six months. OUTCOME MEASURES: Maternal
      sensitivity during dyadic interaction, gestational age, accuracy and reaction
      time in a delayed matching-to-sample task of upright vs. inverted body and face
      stimuli (i.e., inversion effect). RESULTS: Preterm mothers were found to be less
      sensitive than the full-term ones. Higher maternal sensitivity during dyadic
      interaction was associated with lower inversion effect for unfamiliar as compared
      to own infants' bodies. However, preterm mothers and full-term mothers with low
      sensitivity showed comparable inversion effect in perceiving unfamiliar infants'
      faces or bodies. CONCLUSIONS: Preterm birth per se does not directly affect body
      configural processing, but it may be associated to reduced maternal sensitivity,
      ultimately leading to a less refined perception of own infant's cues.

PMID- 30199718
TI  - Erroneous thyroid diagnosis due to over-the-counter biotin.
AB  - OBJECTIVES: Biotin is a component of the vitamin B complex used in standard
      immunoassays to detect serum levels of various hormones and non-hormones,
      including thyrotropin (TSH) and thyroxine. These assays involve a strong bond
      between streptavidin and biotin, which serves as an anchor for measured analytes.
      Large doses of exogenous biotin for the treatment of certain medical conditions
      have resulted in assay interference, causing TSH to be spuriously lowered.
      Smaller doses of biotin found in dietary supplements also have caused assay
      interference. METHODS: We describe four cases in which over-the-counter (OTC)
      biotin caused erroneous thyroid diagnosis and clinical confusion in patients with
      preexisting thyroid disease. Serum TSH and thyroxine were measured by the Vitros
      5600 assay. CONCLUSIONS: Although the biotin-streptavidin interaction is
      sensitive for detecting serum levels of TSH, it is subject to interference by
      exogenous biotin at levels found in OTC products. The widespread use of OTC
      biotin for cosmetic purposes can adversely affect the diagnosis of the entire
      spectrum of functional thyroid disorders. Physicians must carefully and routinely
      question for the use of biotin before thyroid function testing.

PMID- 30199719
TI  - In vivo endogenous proteolysis yielding beta-casein derived bioactive beta
      casomorphin peptides in human breast milk for infant nutrition.
AB  - Objective Beta-casein is a major protein in breast milk and an important source
      for several bioactive peptides that are encrypted within the sequence. Beta
      casomorphins (BCMs) are short-chain proteolytic peptides that are derived from
      the beta-casein protein and have opioid effects in newborns. Human milk is known
      to contain naturally occurring milk-protein-derived bioactive peptides but the
      identification of naturally occurring beta-casein-derived BCMs in human breast
      milk has been limited due to difficulties in the detection of BCM peptides, which
      are small and circulate in low concentrations. Methods The present study aimed to
      identify the naturally occurring BCM peptides from beta-casein in human breast
      milk using liquid chromatography-tandem mass spectrometry. The BCM peptides
      identified in the breast milk were analysed to predict the milk proteases
      responsible for the cleavage patterns using a computational tool EnzymePredictor.
      Results In-depth peptidomics analysis of breast milk samples that were collected
      at different lactation stages during human lactation revealed the presence of
      BCMs including BCM-8, -9, -10, and -11 as well as precursors and truncated forms
      of the original peptide, which suggests that milk protease activity in the
      mammary gland generates biologically relevant BCMs. Conclusions To our knowledge,
      this is the first report to describe the presence of naturally occurring human
      BCM-10 and -11 in breast milk. Our study provides evidence of beta-casein-derived
      BCM peptides in human milk before infant digestion. Proteases that are present in
      milk are likely specific in their proteolysis of beta-casein. The identified
      bioactive BCM-8, -9, -10, and -11 as well as the precursor peptides meet the
      structural requirements to elicit opioid, immunomodulatory, antioxidative, and
      satiety functions in newborns.

PMID- 30199720
TI  - Fishing in greener waters: Understanding the impact of harmful algal blooms on
      Lake Erie anglers and the potential for adoption of a forecast model.
AB  - Harmful algal blooms (HABs) pose public health risks worldwide, because of the
      toxins that they can produce. Researchers have explored the impact of HABs on
      local economies, but know relatively little about the decision-making that
      informs these behaviors that lead to financial losses. Understanding the factors
      that inform this decision-making is critical to developing mitigative solutions.
      This study seeks to understand how HABs in Western Lake Erie affect angler
      decision-making, before evaluating a possible decision-support tool-a harmful
      algal bloom forecast known as the Experimental Lake Erie HAB Tracker. The HAB
      Tracker provides a nowcast and five-day forecast of the spatial distribution and
      transport of Microcystis, the predominant species of harmful algae in Western
      Lake Erie. Data collected using focus groups and surveys were coded to identify
      key themes that influence angler decision-making. The theory of the diffusion of
      innovations provides an analytical framework to evaluate the potential for
      widespread adoption of the HAB forecast among Lake Erie anglers. Analysis of
      emerging themes revealed that Lake Erie anglers face three key decision-points
      when fishing in HABs: whether to fish, where to fish, and whether to eat the
      fish. Five primary variables factored into angler decisions on where and whether
      to fish including 1) perceptions of HAB aesthetics, 2) perceptions of the impact
      of HABs on angler health, 3) perceptions of the impact of HABs on fish, 4)
      communication methods, 5) perceptions of HABs by customers of charter captains.
      Most participants in this study sought to avoid fishing in HABs primarily for
      aesthetic reasons. Recreational anglers are more likely than charter captains to
      adopt the HAB Tracker as a decision-support tool, because it is compatible with
      their information needs and provides a relative advantage over existing sources
      of information. Charter captains are less likely to adopt the HAB Tracker,
      because they rely on their existing knowledge and social network for HAB
      information. If researchers can reduce the complexity of forecast information
      while increasing its accessibility and reliability, then all anglers will be more
      likely to adopt a HAB forecast as a decision-support tool while fishing in Lake
      Erie during bloom season.

PMID- 30199721
TI  - Clearing shrubland and extensive livestock farming: Active prevention to control
      wildfires in the Mediterranean mountains.
AB  - Forest fires are one of the main environmental problems in Mediterranean
      environments and different fire prevention policies have been applied: livestock
      grazing, prescribed fires and a combination of both. However, none present
      satisfactory results. In that context, in 1986 the Regional Government of La
      Rioja started the Plan for Shrub Clearing (PSC), combining shrub clearings and
      livestock grazing to control fires and improve the land management of abandoned
      mountain areas. Our study aims to analyse the effects of shrub clearings on
      forest fires in La Rioja and to compare the main results with those observed in
      Spain in the last 30 years. We apply an interdisciplinary methodology based on
      the analysis of the evolution of cleared areas, the evolution of wildfires in La
      Rioja and Spain, mapping land use and land cover changes, and quantifying the
      combustibility. Results obtained in La Rioja are very positive compared with the
      evolution of Spain, both in the reduction of the number of fires and the burned
      areas. Decreases in the combustible material, fuel load and biomass and in the
      occurrence of fires (>1 ha) were observed. In addition, clearing shrubland and
      extensive livestock provided other environmental benefits (i.e. mosaic
      landscapes, ecosystem services). Finally, this study suggested that they are good
      and sustainable techniques to prevent and control wildfires and they could be
      used as a land management strategy in other Mediterranean areas.

PMID- 30199722
TI  - Efficient bioconversion of organic wastes to value-added chemicals by soaking,
      black soldier fly (Hermetia illucens L.) and anaerobic fermentation.
AB  - Corncob degradation is an issue that needs to be address for it to be further
      utilized as bioenergy. We explored a new comprehensive degradation strategy for
      corncob. First, restaurant wastewater was used to improve the corncob biochemical
      characteristics and partly degrade the lignocelluloses. After the restaurant
      wastewater treatment, the residue was converted using black soldier fly larvae
      (BSFL), and the supernatant was utilized for biogas production by anaerobic
      fermentation. The highest product rates of glucose, xylose, and arabinose were
      obtained at the optimal corncob soaking condition at 75  degrees C, 5 h, and 60
      g/L from lignocellulose. The soaking residue was converted using BSFL for 10
      days, and 24.34% grease yield was extracted. The soaking residue can be utilized
      by BSFL and produce grease, which is similar to other wastes such as rice straw
      and pig manure. The corncob soaking supernatant was utilized for biogas
      production by anaerobic fermentation. The degradation of cellulose,
      hemicellulose, and lignin reached about 27.34%, 45.14%, and 29.33%, respectively.
      A total of 500 mL supernatant mixed with 30% anaerobic sludge under 35 +/- 2 
      degrees C produced about 7.52 L of biogas with about 3.22 L methane. In
      conclusion, the above comprehensive process can effectively degrade
      lignocellulose in corncob and obtain two bioenergy products, namely insect grease
      and biogas.

PMID- 30199723
TI  - Equilibrium and kinetic studies of ferricyanide adsorption from aqueous solution
      by activated red mud.
AB  - In this study, activated red mud (ARM) was used as a new adsorbent for the
      removal of ferricyanide anions from aqueous solution. Based on the percentage of
      ferricyanide removal and ferricyanide adsorption capacity, optimum conditions
      were evaluated using the response surface method (RSM) and central composite
      design (CCD). In optimum conditions (pH = 5.6, adsorbent dosage of 2.59 g,
      ferricyanide concentration of 60 ppm and contact time of 60 min), the percentage
      of ferricyanide removal and ferricyanide adsorption capacity were obtained as
      79.6% and 1.8 mg/g, respectively. The kinetics and equilibrium studies were
      evaluated by considering the effective parameters including pH and ferricyanide
      concentration. Kinetic studies were evaluated by kinetic models of pseudo first
      order, pseudo-second-order (four different linearized forms), Elovich and
      intraparticle diffusion. The results of the kinetic study indicated that the
      mechanism of ferricyanide adsorption onto the ARM adsorbent is a chemisorption
      interaction by a fast ferricyanide adsorption onto ARM and subsequently the slow
      diffusion of ferricyanide ions into the ARM inner adsorption sites. The
      equilibrium studies showed that the adsorption process followed the Langmuir
      model in which ferricyanide adsorption onto ARM was homogeneous with monolayer
      adsorption. The results indicated that the activation process of red mud improved
      adsorbent efficiency and increased the adsorption capacity.

PMID- 30199724
TI  - Eyes wide shut: Exploring practices of negotiated ignorance in water resources
      modelling and management.
AB  - Formalised methods to address uncertainty are becoming the norm in hydrological
      modelling, yet they remain fragmented and highly academic, thus limiting their
      utility for practitioners. Using a qualitative, empirical study of the PIREN
      Seine program in France, this paper explores the proccesses behind this trend in
      an effort to elucidate its prevalence despite inherent limitations when applied
      to a decision-making context. We identify: 1/ displacement of 'uncomfortable
      knowledge', 2/ fragmented responsibility, 3/ confidence, and 4/ relational
      framing as interconnected factors, which concurrently support the production of
      scientific knowledge and the social construction of ignorance, whether it be
      wilful or intentional. We posit that ignorance is implicitly negotiated among
      researchers and practitioners in order to reconcile cognitive dissonance and
      maintain confidence, thereby allowing water managers to take action in the face
      of uncertainty. Finally, we put forth the notion that having our 'eyes wide shut'
      can be interpreted in two ways: one facilitates the normalisation of ignorance,
      leaving us vulnerable to unexpected surprises; the other promotes transparent and
      explicit communication in support of more adaptive and robust decisions.

PMID- 30199725
TI  - The state-of-the-art system dynamics application in integrated water resources
      modeling.
AB  - In recent years, water resources management has become more complicated and
      controversial due to the impacts of various factors affecting hydrological
      systems. System Dynamics (SD) has in turn become increasingly popular due to its
      advantages as a tool for dealing with such complex systems. However, SD also has
      some limitations. This review contains a comprehensive survey of the existing
      literature on SD as a potential method to deal with the complexity of system
      integrated modeling, with a particular focus on the application of SD to the
      integrated modeling of water resources systems. It discusses the limitations of
      SD in these contexts, and highlights a number of studies which have applied a
      combination of SD and other methods to overcome these limitations. Finally, our
      study makes a number of recommendations for future modifications in the
      application of SD methods in order to enhance their performance.

PMID- 30199726
TI  - Facing the future for grassland restoration - What about the farmers?
AB  - In line with the 2010 Aichi Convention for Biological Diversity, the European
      Union has a goal to restore 15% of degraded ecosystems and their services by the
      year 2020 (target 2, Europe 2020). This includes restoration of semi-natural
      grasslands (SNGs). Management of both intact and restored SNGs is dependent on
      people's willingness to manage them. Due to low profitability, management
      abandonment still occurs all over Europe, which highlights the need to raise
      farmers' and landowners' perspectives. In this study, we combined survey data and
      in-depth interviews with farmers/landowners managing previously restored SNGs, to
      understand how they perceive the restoration process, the outcome and future
      management. Survey and interview data were analysed in relation to biodiversity
      and Agri-environmental payments data from the restored sites. Almost all
      respondents considered the restoration successful and the re-inventoried restored
      SNGs also showed an increase in plant diversity. Nevertheless, 10% of the
      restored SNGs were abandoned again post-restoration and 40% of the respondents
      were unsure if they would continue the management in the future. Abandoned
      management may cause a negative trend in terms of decreased biological, cultural
      and aesthetic values, in the local community, as well as for the society in
      general. Most respondents explained a strong dependency on Agri-environmental
      payments, both as a restoration incentive and for post-restoration management.
      Also non-financial support from authorities in form of feedback and advice was
      requested, as well as support from the local community and society as a whole.
      Future management in a longer time perspective was strongly coupled to the farm
      economy, i.e. received Agri-environmental payments at farm-level and profit from
      selling agricultural products, and whether the farmers had successors. We
      conclude that both social and ecological factors, here farm economy, authority
      support and proper management, must be in place for long-term success of
      grassland restoration.

PMID- 30199727
TI  - Bioremediation of chromium contaminated water by diatoms with concomitant lipid
      accumulation for biofuel production.
AB  - Hexavalent chromium compounds such as chromate and dichromate, commonly
      designated as Cr (VI) compounds, are widely used heavy metals in different
      industries and are considered highly toxic to most life forms. Unfortunately,
      they have become a major pollutant of groundwater and rivers around dichromate
      using industries. Bioremediation is widely used to decrease the amount of
      dichromate in wastewater but requires large amounts of precious fresh water. Here
      we tested two marine micro-algal species, Phaeodactylum tricornutum strain
      CCY0033 and Navicula pelliculosa strain CCMP543, for their ability of dichromate
      bioremediation and concomitantly producing lipids that can serve as biofuel.
      Dichromate tolerance of the strains was investigated under different growth
      conditions in order to obtain high biomass yields, high lipid accumulation and
      high dichromate removal from the medium. Both algal strains grew well and
      produced high biomass in media containing up to 1 mg of dichromate per liter.
      Variations in growth conditions revealed that dichromate removal from the medium
      correlated positively with biomass yield. Dichromate removal using living cells
      was in the same order of magnitude as with autoclaved dead cells or when using
      extracted extracellular polymeric substances (EPS). This suggests biosorption of
      dichromate to cell-associated polymeric substances as the major mechanism of the
      bioremediation process. For both strains, optimal dichromate removal and lipid
      production were achieved at a light intensity of 55 MUmol m-2s-1 and at a sodium
      nitrate concentration of 3 mM. The optimal temperature for dichromate removal and
      lipid production was 23  degrees C for P. tricornutum and 27  degrees C for N.
      pelliculosa. Compared to P. tricornutum strain CCY0033, N. pelliculosa strain
      CCMP543 produced an overall higher lipid yield under these conditions.

PMID- 30199728
TI  - Comparison of the efficiency of chitinous and ligneous substrates in metal and
      sulfate removal from mining-influenced water.
AB  - Mining-influenced water (MIW) remediation is challenging, not only due to its
      acidity and high metal content, but also due to its presence in remotely located
      mine sites with difficult surrounding environments. An alternative to common
      remediation technologies, is the use of sulfate-reducing bacteria (SRB) to
      achieve simultaneous sulfate reduction and metal removal in on-site anaerobic
      passive systems. In these systems, the organic carbon source (substrate)
      selection is critical to obtaining the desired effluent water quality and a
      reasonable treated volume. In this study, we evaluated the use of two different
      substrates: a chitinous product obtained from crushed crab shells, and a more
      traditional ligneous substrate. We put the substrates, both with and without
      water pretreatment consisting of aeration and pH adjustment, in anaerobic
      experimental columns. The treatment with the chitinous substrate was more
      effective in removing metals (Al, Cu, Fe, Cd, Mn, Zn) and sulfate for a longer
      period (458 days) than the ligneous substrate (78 days) before suffering Zn
      breakthrough. The reactors fed with pretreated water had longer operational
      periods and lower metals and sulfate concentrations in the effluent than those
      with untreated influent water. Zn was consistently removed to levels <0.3 mg/L
      for 513 days in the chitinous substrate columns, while levels <0.3 mg/L were
      maintained for only 140 days in the ligneous substrate pretreated column. The
      highest sulfate removal rates achieved in this study were in the range of 5-6
      mol/m3/d for the chitinous substrate and 1-2 mol/m3/d for the ligneous substrate.
      Overall, the chitinous substrate proved to be more efficient in the removal of
      all the aforementioned metals and for sulfate when compared to the ligneous
      substrate. This could be the determinant when selecting a substrate for passive
      systems treating acidic MIW, particularly when Zn and Mn removal is necessary.

PMID- 30199729
TI  - Production of high-octane gasoline via hydrodeoxygenation of sorbitol over
      palladium-based bimetallic catalysts.
AB  - A methodology for the synthesis of gasoline-range fuels from carbon neutral
      resources is introduced. Sorbitol, a sugar-based compound, was employed as a raw
      material because the compound is readily obtained from cellulose. Gasoline-range
      hydrocarbons were produced via hydrodeoxygenation (HDO) on zirconium phosphate
      supported Pd-bimetallic (Pt-Pd, Ru-Pd, Ni-Pd, Fe-Pd, Co-Pd, W-Pd) catalysts.
      Among the tested catalysts, the bimetallic W-Pd/ZrP catalyst exhibited the
      highest yield of gasoline products, peaking at ~70%. However, with the bimetallic
      Fe-Pd and Co-Pd catalysts, high-octane gasoline products were made (research
      octane number (RON) of the products was higher than 100). The Fe-Pd catalyst also
      showed the highest initial activity for the HDO of sorbitol. This study
      demonstrates that HDO in the Pd-system is a promising option to produce high
      quality gasoline-range hydrocarbons from lignocellulosic biomass.

PMID- 30199730
TI  - Critical evaluation of mechanism responsible for biomass abatement during
      electrochemical coagulation (EC) process: A critical review.
AB  - This is a first review paper that delineates fundamental disinfection mechanism
      undergoes during the simple electrochemical coagulation (EC) process. The
      elucidation of detailed mechanistic phenomenon of EC process involved would help
      to enhance the disinfection efficiency. In this context, the biomass (bacteria,
      virus and algae) abatement mechanism by EC is critically reviewed and
      rationalized based on the experimental demonstration performed from the recent
      decade. Whereas, the effect of most significant abiotic operating parameters,
      dissolved contents and bacteria cell wall composition on biomass reduction are
      explored in detail. From these analyses, physical removal and chemical
      inactivation routes are identified for bacteria abatement mechanism during the EC
      process using sacrificial electrodes. Which includes (i) enmeshment of microbial
      contaminants by EC flocs, (ii) sweeping flocculation is preferentially for
      destabilization of negatively charged biomass, and (iii) inactivation/attenuation
      of micro-organism cell walls by electrochemically induced reactive oxygen species
      (ROS) or direct interaction of electric field. Perhaps, the overall abatement
      mechanism attributes due to the aforementioned phenomenon endures independently
      and/or synergistically during the EC process. Nonetheless, to obtain better
      understanding of virus and algae abatement mechanism, we require more
      experimental investigation on algae and virus removal. Eventually, more intensive
      research efforts on biomass attenuation by EC are most important to reinforce
      this claim.

PMID- 30199731
TI  - Aloe vera waste biomass-based adsorbents for the removal of aquatic pollutants: A
      review.
AB  - Aloe vera has been cultivated for many centuries for its beneficial properties,
      finding application in a wide range of medical and health products. Nowadays, the
      research has also focused on an alternative use of Aloe vera which is related to
      environmental applications such as clean water technology/wastewater treatment
      process. In recent years, biosorption has been shown to be a cost-effective and
      efficient alternative method for removing various pollutants from wastewater and
      water. This work provides a comprehensive review on using Aloe vera waste biomass
      based sorbents, as well as modified counterparts, for the removal of heavy
      metals, dyes and other pollutants from aqueous media. The discussed biosorbents
      have been grouped in five categories based on the treatment of the Aloe vera
      leaves. Adsorption mechanisms, in addition to the significant factors influencing
      sorption capability like physical and chemical properties of the adsorbent,
      initial concentration, initial pH and temperature of the solution, dosage and
      contact time, have been discussed in detail. Furthermore, the applied equilibrium
      and kinetic models have been also summarized. The history, taxonomy, botany, and
      applications of Aloe vera are also presented in brief.

PMID- 30199732
TI  - A foreign body in inguinal canal: A case report.
AB  - INTRODUCTION: Inguinal bladder hernias are rare incidents accounting for 1-3% of
      all inguinal hernia. Most of those cases are discovered intraoperatively
      accounting for the high incidence of bladder injuries during the repair. Symptoms
      can be variable depending on the size of the herniated bladder. PRESENTATION OF
      CASE: We present here a 70 years old obese male patient, with history of CVA & on
      regular Aspirin ingestion. He presented to the ER as a case of intestinal
      obstruction due to suspicion of strangulated inguinal hernia based on an unclear
      Ultrasound picture. He underwent an emergency exploration of the hernia where the
      balloon of a Foley's catheter was found inside a diverticulum of the urinary
      bladder, herniated through an Ogilvie hernia. DISCUSSION: Ogilvie hernia is a
      rare incident that happens mostly in elderly males. The herniated part contains
      prevesical fat, bladder andor loops of intestines. Diagnosis must be made
      preoperatively through CT scan or Cystourethrogram. First line management
      involves surgical reduction of the bladder and hernia repair. Resection of the
      herniated part is generally limited to necrotic tissues. CONCLUSION: Surgeons
      must have high index of suspicion for elderly obese males with inguinal hernias
      and urinary or intestinal obstruction symptoms. Careful preoperative planning
      must be made to avoid repair associated bladder injuries.

PMID- 30199733
TI  - Intra-articular lipoma arborescens of the knee: A report of two cases with
      bilateral localization.
AB  - INTRODUCTION: Lipoma arborescens is a very rare pseudo-tumoral lesion of unknown
      etiology, characterized by lipomatous infiltration of subsynovial stroma,
      bilateral involvement is exceptional, only eight cases are reported in the
      literature. PRESENTATION OF CASE: We report the very rare case of two men
      presented at our department with complaints of swelling of both knees and
      intermittent joint effusion, Surgical biopsy revealed Lipoma arborescens in both
      cases. Open total synovectomy was performed. Follow-up evaluation showed no signs
      of recurrence. DISCUSSION AND CONCLUSION: Lipoma arborescens is a rare entity,
      the unilateral form affecting the knee is the most common, with a predilection
      for suprapellar recess. Magnetic resonance imaging (MRI) is the examination of
      choice showing multiple villous proliferation of the synovium and fat-like cells,
      with a fatty signal on all sequences. Treatment by open or arthroscopic
      synovectomy offers the best outcomes.

PMID- 30199735
TI  - Heat resistance, membrane fluidity and sublethal damage in Staphylococcus aureus
      cells grown at different temperatures.
AB  - In this work the influence of growth temperature (10-42  degrees C) on
      Staphylococcus aureus heat resistance was studied, and its relationship with the
      ability of cells to repair sublethal damages and with membrane fluidity was
      evaluated. Non-linear, convex from above survival curves were obtained, and
      therefore a special case of the Baranyi model was used to fit them. For
      exponential phase cells, heat resistance did not change with growth temperature
      in the range between 10 and 37  degrees C, but cells grown at 42  degrees C were
      significantly more resistant, showing D58 and shoulder length (sl58) values 2.5
      and 4 times greater than the others, respectively. For stationary growth phase
      cells, an increase in growth temperature above 20  degrees C resulted in an
      increase in D58 values, and cells grown at 42  degrees C also displayed the
      highest D58 and sl58 values. The increased heat resistance at 58  degrees C of
      stationary growth phase cells grown at higher temperatures was coincident with
      the appearance of a higher proportion of sublethally damaged cells capable of
      recovery and outgrowth in non-selective medium. Membrane fluidity was measured at
      treatment temperatures, and it was observed that those cells with more rigid
      membranes displayed greater heat resistance (Pearson coefficient = 0.969***).
      Additionally, S. aureus cells whose membrane was fluidized through exposure to
      benzyl alcohol were notably sensitized against the action of heat, in a
      concentration-dependent manner. Results obtained in this research indicate that
      membrane physical state could be an important factor determining the survival
      capacity of bacterial cells to a heat treatment.

PMID- 30199736
TI  - Reduction of Salmonella and Shiga toxin-producing Escherichia coli on alfalfa
      seeds and sprouts using an ozone generating system.
AB  - Several outbreaks of illness have been associated with consumption of alfalfa
      sprouts contaminated with Shiga toxin-producing Escherichia coli (STEC) and
      Salmonella. The ozone application was investigated as an intervention. Alfalfa
      seeds were inoculated with cocktails of 3 Salmonella strains, including serotypes
      Typhimurium, Agona and Saintpaul, and 3 strains of Shiga toxin-producing
      Escherichia coli (STEC) including serotypes O104:H4, O157:H7 and O121:H19 with a
      final load of 7.0 log CFU/ml. Then, the inoculated seeds, and the sprouts
      obtained from these seeds were separately subjected to aqueous ozone treatment
      containing (5 mg/L) ozone for varied times of exposure. The mean log reductions
      for Salmonella achieved on seeds after 10, 15, and 20 min of ozone exposure were
      1.6 +/- 0.5, 1.7 +/- 0.3, 2.1 +/- 0.5, respectively and 1.5 +/- 0.4, 1.6 +/- 0.4,
      2.1 +/- 0.5 for STEC, respectively. For sprouts obtained from the inoculated
      seed, the mean log reductions for Salmonella after 10, 15, and 20 min exposure
      times were 0.7 +/- 0.2, 1.1 +/- 0.4, 3.6 +/- 0.2, respectively, whereas the mean
      log reductions for STEC were 0.7 +/- 0.1, 1.2 +/- 0.3 and 1.8 +/- 0.2,
      respectively. At each contact time, there were no differences in log reductions
      between pathogens on seeds (P > 0.05), whereas on sprouts, the reductions
      obtained at 20 min were significantly greater (P < 0.05) for Salmonella than for
      STEC. On both seeds and sprouts, the exposure time had significant (P < 0.05)
      effects on log reductions of Salmonella and STEC. The weight, color properties
      and shelf life of ozonated sprouts were also tested. The ozonation did not have
      negative effects on germination (%), color and mass of sprouts in comparison with
      the controls. This study confirmed that it is possible to substantially reduce
      Salmonella and STEC by using a low ozone concentration (5 mg/L) and reduce food
      safety risk with less concern about the safety for processing workers of this
      treatment, this without affecting seed germination. This procedure may be a
      promising intervention to reduce Salmonella and STEC from alfalfa seeds and
      sprouts.

PMID- 30199734
TI  - Clinical and radiological characteristics of neuromyelitis optica spectrum
      disorder in the North Egyptian Nile Delta.
AB  - BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune
      demyelinating disorder of the central nervous system that was previously thought
      to be a subtype of multiple sclerosis (MS). Epidemiology studies of NMOSD are
      rare in both Middle East and North African countries. To our knowledge, there are
      no such studies in Egypt. Herein, we describe a case series of NMOSD patients
      from North Egyptian Nile Delta region and compare them to NMOSD in other parts in
      the Middle East and the world. METHODS: This is a case series study of NMOSD
      patients who were seen at the neuroimmunology clinic, Elhadara Hospital,
      University of Alexandria, Egypt, from January 2017 to January 2018. We describe
      their clinical, serological and radiological features. RESULTS: Our study
      identified twenty Egyptian patients, all of who fulfilled the 2015 international
      NMOSD diagnostic criteria. Ten tested positive for AQP4 antibodies in the serum
      while the other ten were seronegative. The mean age at onset was 27.8 years with
      an average disease duration of 6.8 years. There was a strong female predominance
      with a ratio of 5.6:1. We identified clinical features of the cohort that differ
      from those reported in other worldwide studies. INTERPRETATION: This is the first
      NMOSD case series in Egypt. Despite some limitation in testing and access to
      care, there are features of our NMOSD cases that appear to be different from
      other worldwide cohorts reported in the literature.

PMID- 30199737
TI  - Listeria monocytogenes colonization in a newly established dairy processing
      facility.
AB  - The presence and colonization of Listeria monocytogenes were investigated in a
      newly established dairy processing plant during a one-year period. A total of 250
      non-food contact surfaces, 163 food contact surfaces, 46 personnel and 77 food
      samples were analyzed in two different buildings according to the cheese
      production chain. Initial steps, including salting, are performed in building I
      (old facility), while the final steps, including ripening, cutting and packaging,
      are performed in building II (new facility). Overall, 218 samples were collected
      from building I and 318 from building II. L. monocytogenes isolates were subtyped
      by PFGE and MLST, and a questionnaire about quality measures was completed. The
      overall prevalence of L. monocytogenes was 8.40%, and while the presence of the
      pathogen was observed just during the first sampling in building I, L.
      monocytogenes was found in building II at the third sampling event. The salting
      area in building I had the highest proportion of positive samples with the
      highest diversity of PFGE types. Moreover, L. monocytogenes PFGE type 3 (sequence
      type -ST- 204) was first detected in building II in the third visit, and spread
      through this building until the end of the study. The answers to the
      questionnaire implied that lack of hygienic barriers in specific parts of the
      facilities and uncontrolled personnel flow were the critical factors for the
      spread of L. monocytogenes within and between buildings. Knowledge of the
      patterns of L. monocytogenes colonization can help a more rational design of new
      cheesemaking facilities, and improve the food safety within current facilities.

PMID- 30199739
TI  - Improved bovine in vitro embryo production with sexed and unsexed sperm selected
      by chemotaxis.
AB  - Assisted reproductive techniques (ART) have been widely used in farm animals in
      the last decades. Sexed cryopreserved spermatozoa, ovum pick up, in vitro embryo
      production and transfer constitute the ART that have revolutionized the dairy
      industry. However, the efficiency of some of these techniques is still low due in
      part to sperm quality, which influences fertilization, embryo development and
      implantation. The Sperm Selection Assay (SSA), based on sperm chemotaxis towards
      progesterone, provides a sperm subpopulation enriched with spermatozoa that are
      capacitated, with intact DNA and low level of oxidative stress. Since the SSA
      selects a sperm subpopulation at optimum physiological state, the application of
      the SSA may improve the efficiency of the current ART. The aim of this study was
      to adapt the SSA for unsexed and sexed bovine frozen-thawed semen samples, and
      then to test whether sperm selection by the SSA improves the cleavage rate of
      bovine embryos in vitro. The optimal SSA conditions to obtain the higher sperm
      accumulation percentage given by chemotaxis were the same for both unsexed and
      sexed semen samples. Thus, sperm accumulation in W2 was significantly higher
      when: 2 million sperm per mL were placed in W1 (unsexed samples: 12 +/- 1%, p =
      0.002; sexed samples: 14 +/- 3%, p = 0.02); 1 pM progesterone was placed in W2
      (unsexed sample: 9 +/- 1%, p = 0.009; sexed samples: 11 +/- 2%, p = 0.02); and to
      incubate the SSA device for 10 min (unsexed samples: 17 +/- 2%, p = 0.007; sexed
      samples: 10 +/- 1%, p = 0.004). We found that the quality of spermatozoa
      recovered from W2 in unsexed and sexed semen was enhanced. Thus, the capacitation
      index was significantly increased (unsexed samples: 1.75 +/- 0.1, p = 0.0001;
      sexed samples: 1.76 +/- 0.2, p = 0.004), while DNA fragmentation index was
      significantly decreased (unsexed samples: 0.33 +/- 0.07, p = 0.0003; sexed
      samples: 0.32 +/- 0.04, p = 0.002). Moreover, the cleavage index of oocytes
      fertilized with either unsexed or sexed SSA-selected sperm was significantly
      improved (unsexed samples: 3.2 +/- 0.4, p = 0.0001; sexed samples: 2.3 +/- 0.33,
      p = 0.03). Thus, we show that the SSA can be used to recruit a bovine sperm
      subpopulation at optimal functional state regardless of whether the sample is
      previously sexed, and that this optimal state improves bovine embryo cleavage
      rate.

PMID- 30199738
TI  - A randomised controlled trial of memory flexibility training (MemFlex) to enhance
      memory flexibility and reduce depressive symptomatology in individuals with major
      depressive disorder.
AB  - : Successful navigation within the autobiographical memory store is integral to
      daily cognition. Impairment in the flexibility of memory retrieval can thereby
      have a detrimental impact on mental health. This randomised controlled phase II
      exploratory trial (N = 60) evaluated the potential of a novel intervention drawn
      from basic science - an autobiographical Memory Flexibility (MemFlex) training
      programme - which sought to ameliorate memory difficulties and improve symptoms
      of Major Depressive Disorder. MemFlex was compared to Psychoeducation (an
      evidence-based low-intensity intervention) to determine the likely range of
      effects on a primary cognitive target of memory flexibility at post-intervention,
      and co-primary clinical targets of self-reported depressive symptoms and
      diagnostic status at three-month follow-up. These effect sizes could subsequently
      be used to estimate sample size for a fully-powered trial. Results demonstrated
      small-moderate, though as expected statistically non-significant, effect sizes in
      favour of MemFlex for memory flexibility (d = 0.34, p = .20), and loss of
      diagnosis (OR = 0.65, p = .48), along with the secondary outcome of depression
      free days (d = 0.36, p = .18). A smaller effect size was observed for between
      group difference in self-reported depressive symptoms (d = 0.24, p = .35). Effect
      sizes in favour of MemFlex in this early-stage trial suggest that fully-powered
      evaluation of MemFlex may be warranted as an avenue to improving low-intensity
      treatment of depression. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier
      NCT02371291.

PMID- 30199740
TI  - Resynchronization improves reproductive efficiency of suckled Bos taurus beef
      cows subjected to spring-summer or autumn-winter breeding season in South Brazil.
AB  - The objective of the present study was to evaluate the effect of estrus
      resynchronization (RE) after the first Timed Artificial Insemination (TAI)
      protocol on reproductive efficiency of suckled Bos taurus beef cows (n = 1052;
      Angus and Brangus) subjected to two different breeding season (BS) in Rio Grande
      do Sul, Brazil. In experiment 1, cows were maintained in native pasture on
      conventional BS (spring-summer), and in experiment 2, cows were maintained in a
      grazing area cultivated in an integrated crop-livestock system on modified BS
      (autumn -winter). Experiment 1 cows (n = 92) were randomly distributed in two
      reproductive managements: 1) TAI at the first day of the BS (Day 0), followed by
      natural service (NS) on day 10 until the end of the BS (TAI + NS; n = 45) or, 2)
      TAI on day 0, followed by RE 22 days after the first TAI and then followed by NS
      on day 42 until the end of the BS (TAI + RE22 + NS; n = 47). Experiment 2 cows (n
      = 960) were subjected to one of four reproductive managements: 1) only NS for 90
      days of the BS (NS; n = 266); 2) TAI on day 0, followed by NS on day 10 until the
      end of the BS (TAI + NS; n = 200); 3) TAI on day 0, followed by RE 22 days after
      the first TAI and then followed by NS on day 42 until the end of the BS (TAI +
      RE22 + NS; n = 249) or, 4) TAI on day 0, followed by RE 30 days after the first
      TAI and then followed by NS on day 50 until the end of the BS (TAI + RE30 + NS; n
      = 245). In experiment 1, conception rate after first TAI was similar for
      treatments TAI + NS (42%, 19/45) and TAI + RE22 + NS (48%, 23/47; P = 0.4107).
      Total pregnancy rates at day 60 of the BS were 55.6% and 66.6% for TAI + NS and
      TAI + RE22 + NS, respectively (P = 0.006). In experiment 2, only 3% of the
      females submitted to NS were pregnant 30 days after the onset of BS, a lower rate
      compared to other groups (TAI + NS = 40%; TAI + RE22 + NS = 39.8%; TAI + RE30 +
      NS = 40%; P < 0.001). At 70 days of the BS, the groups TAI + RE22 + NS and TAI +
      RE30 + NS obtained greater pregnancy rate (66.3% and 69.4%, respectively) than
      other groups (NS = 16.9%; TAI + NS = 48%; P < 0.001). Pregnancy rate at the end
      of BS was greater in RE groups (TAI + RE22 + NS = 81.5%; TAI + RE30 + NS = 83.7%)
      than the NS (45.1%) or TAI + NS (71%). In conclusion, resynchronization increases
      pregnancy rate per AI (P/AI) and reproductive efficiency of suckled Bos taurus
      beef cows during spring-summer or autumn-winter breeding season in natural
      pasture or cultivated pasture, respectively.

PMID- 30199742
TI  - HIV treatment scale-up: a critical step to controlling HIV epidemic in a resource
      limited country.
AB  - OBJECTIVES: The study was conducted to determine the trend in HIV treatment
      coverage among people living with HIV and to evaluate effectiveness of the
      national antiretroviral treatment (ART) programme in reducing new infections in a
      mixed HIV epidemic nation, Nigeria. STUDY DESIGN: Ecological cross-sectional
      study. METHODS: The study utilized national HIV programme service data and
      National HIV/AIDS and Reproductive Health Survey (NARHS) data for 36 states and
      Federal Capital Territory from 2012 to 2015 in Nigeria. Chi-squared test for
      trend was conducted to determine differences in ART coverage across the years. We
      correlated 2015 ART coverage with HIV prevalence Annual Rate of Reduction (ARR)
      between 2012 and 2015. A linear regression model was fitted to predict the HIV
      prevalence ARR in relation to ART coverage and adjusted for the effect of socio
      behavioral interventions (coverage of condom-use among male). RESULTS: Nigeria
      has recorded steady progress with HIV treatment coverage with an annual rate of
      progress of 18.25%, P < 0.001; however, huge gaps still exist. Females and adults
      had higher odds of receiving ART. HIV prevalence annual reduction rate was higher
      for states that had higher ART coverage (r = 0.4; P = 0.02). Our analysis
      indicated that a 10% increase in ART coverage was associated with a 4% increase
      in the annual rate of reduction for HIV prevalence (adjusted beta = 0.4; 95%
      confidence interval: 0.1-0.8; P = 0.01). CONCLUSIONS: Regardless of the low ART
      coverage, our analysis supports the evidence base to inform accelerated access to
      HIV treatment for population Nigeria and other similar resource-limited settings
      to make ending HIV by 2030 a reality.

PMID- 30199741
TI  - Evaluating reproductive performance of three estrus synchronization protocols in
      Ghezel ewes.
AB  - Although estrus synchronization considered valuable management tools for
      improving reproductive performance of ewes, their high expenses and complicated
      usage prevent sheep farmers to apply these techniques. Therefore, the present
      study was designed to compare three protocols of estrus synchronization on
      reproductive performance of Ghezel ewes. For this reason, 27 Ghezel ewes were
      assigned to three estrus synchronization treatment groups based on a completely
      randomized design included: progestogen sponge for 12 days + 500 IU eCG at the
      time of sponge withdrawal (P4eCG group, expensive synchronization), two doses of
      75 MUg cloprostenol with 12 days interval (CLO group, economical
      synchronization), and CLO +500 IU eCG at day 12 (CLOeCG group, moderately priced
      synchronization). Four consecutive blood samples were also collected during the
      experiment to evaluate progesterone concentrations. The results of the present
      experiment showed that pregnancy and lambing rates of the first estrus as well as
      blood progesterone concentration were not affected by the treatments (P > 0.05),
      though total pregnancy and lambing rates were higher in both P4eCG and CLOeCG
      groups (P < 0.01). Accordingly, both P4eCG and CLOeCG protocols successfully
      improved reproductive traits of ewes, though CLOeCG protocol is an advisable
      technique for sheep farmers through its moderate price, simple application, and
      high reproductive performance.

PMID- 30199743
TI  - An experimental investigation into the transmission of antivax attitudes using a
      fictional health controversy.
AB  - RATIONALE: Although vaccines are an invaluable weapon in combatting diseases,
      they are often surrounded by controversy. Vaccine controversies usually arise
      with the claims of some parents or doctors who link vaccines to harmful outcomes.
      These controversies often negatively affect vaccination coverage. OBJECTIVES:
      This experiment simulated a vaccine controversy to understand which content
      features of vaccination-related information are well transmitted and how this
      transmission affects vaccine intention. METHOD: All participants (N = 64) read
      two conflicting views (pro- and anti-) about a fictional vaccine ('dipherpox
      vaccine'). These conflicting views were held by a parent and a doctor, whose
      views varied across conditions. This information was transmitted along linear
      chains of four participants who recalled it and the product of their recall was
      passed to the next participant within their chain. They also responded whether
      they would vaccinate or not. RESULTS: The experience-based view held by the
      parent was better transmitted than the medical-based view held by the doctor,
      while the pro-vaccine and anti-vaccine views were similarly transmitted. Despite
      all the participants having neutral or positive attitudes towards vaccines in
      general, 39.1% of them decided not to vaccinate. Nevertheless, vaccination
      attitude was the strongest predictor of vaccination intention. The less positive
      participants' attitudes were towards vaccines in general, the less likely they
      were to vaccinate against dipherpox after exposure to the controversy.
      CONCLUSION: The results suggest that vaccination campaigns may be made more
      effective by including personal experiences of the negative consequences of non
      vaccination.

PMID- 30199745
TI  - Go/no-go training affects frontal midline theta and mu oscillations to passively
      observed food stimuli.
AB  - The mere perception of high-calorie food items can trigger strong action
      tendencies towards these foods. Go/no-go training has successfully been applied
      to reduce such action tendencies. This study investigated the
      electrophysiological mechanisms that may underlie the beneficial effects of go/no
      go training on food consumption. EEG was measured while 19 participants passively
      observed pictures of food and non-food items, both before and after the go/no-go
      training. During training, 50% of the food and non-food items were consistently
      paired with a go/no-go response. After training, food items that had been
      associated with a response induced larger mu desynchronization at electrodes over
      sensorimotor regions, whereas food items that had been associated with
      withholding from responding induced larger increases in theta power at frontal
      midline electrodes. These findings suggest that the exerted cognitive control
      during go/no-go training with attractive food stimuli may become associated with
      these stimuli and signal the required level of control during subsequent
      encounters.

PMID- 30199744
TI  - Preliminary support for the role of reward relevant effort and chronotype in the
      depression/insomnia comorbidity.
AB  - BACKGROUND: The presence of insomnia in the context of depression is linked to a
      number of poor outcomes including reduced treatment response, increased
      likelihood of relapse, and greater functional impairment. Given the frequent co
      occurrence of depression and insomnia, research into systems and processes
      relevant to both disorders, specifically reward processing and circadian rhythm
      disruption, may help parse this complex comorbidity. METHODS: A pilot study was
      conducted on a sample of 10 veterans with clinically significant depression and
      insomnia symptoms. Participants completed objective (actigraphy) and subjective
      (sleep diary) assessments of sleep, self-reports of chronotype, and behavioral
      tasks assessing reward relevant effort before and after 6 sessions of Cognitive
      Behavioral Therapy for Insomnia. RESULTS: Insomnia and depression significantly
      improved following CBT-I. Subjective sleep parameters significantly improved with
      large effect sizes. Actigraphy results were nonsignificant, but effect sizes for
      sleep efficiency and onset latency were in the medium range. Chronotype shifted
      significantly toward morningness following CBT-I, and an earlier chronotype at
      baseline was associated with increased reward effort following treatment. Changes
      in chronotype, depression and insomnia were not associated with changes in
      effort. LIMITATIONS: Findings are limited by small sample size and lack of
      randomized control group. CONCLUSIONS: Findings should be interpreted as
      hypothesis generating in the service of furthering research aimed at uncovering
      potential mechanisms underlying the depression/insomnia comorbidity. Analyses of
      sleep data in extant datasets of reward processing impairments in depression as
      well as original projects aimed at exploring potential sleep, circadian rhythm,
      and reward interactions in depression are encouraged.

PMID- 30199746
TI  - Morphology and ultrastructure of the infrabuccal pocket and its lining epithelium
      in workers of Ectomomyrmex javanus (Hymenoptera: Formicidae).
AB  - This paper describes the morphology and ultrastructure of the infrabuccal pocket
      in workers of the carnivorous ant Ectomomyrmex javanus, using SEM and TEM. The
      infrabuccal pocket is a flexible bag with a diameter of 330 +/- 30 MUm. In its
      anterior part, the pocket wall reaches a thickness of 24.45 +/- 3.45 MUm, which
      is thicker than the wall lining the rest of the infrabuccal pocket, where it
      measures 6.87 +/- 1.12 MUm. The epidermal cells of the wall form a thickened
      epithelium with a thickness of 10.18 +/- 2.50 MUm. There are different kinds of
      hairs inside the pocket, that help in filtering solid pellets. Literature data on
      the infrabuccal pocket are limited and the function of the thicker epithelium is
      not yet known. It may provide mechanical strength as the pocket undergoes daily
      size changes because of the filling up and spitting out of pellets.

PMID- 30199747
TI  - Stability control for breath analysis using GC-MS.
AB  - Gas chromatography mass spectrometry (GC-MS) instruments provide researchers and
      clinicians with a vast amount of information on sample composition, thus these
      instruments are seen as gold standard in breath analysis research. However, there
      are many factors that can confound the data measured by GC-MS instruments. These
      factors will make interpretation of GC-MS data unreliable for breath analysis
      research. We present in this paper detailed studies of two of these factors:
      instrument variation over time and chemical degradation of known biomarkers
      during storage in sorbent tubes. We found that a single quadrupole MS showed
      larger variability in measurements than a quadrupole time-of-flight MS when the
      same mixture of chemical standards was analysed for a period of up to 8 weeks. We
      recommend procedures of normalising the data. Moreover, the stability studies of
      breath biomarkers like thioethers, previously found indicative of malaria, showed
      that there is a need to store the samples in sorbent tubes at low temperature, 6 
      degrees C, for no more than 20 days to avoid the total decay of the chemicals.

PMID- 30199750
TI  - Relationship between serum homovanillic acid, DRD2 C957T (rs6277), and hDAT A559V
      (rs28364997) polymorphisms and developmental stuttering.
AB  - The involvement of the brain dopamine system in the pathophysiology of
      developmental stuttering has been previously suggested. In the present study, we
      aimed to investigate the relationship between developmental stuttering in
      children and the levels of serum homovanillic acid (HVA), dopamine D2 receptor
      (DRD2) C957T (rs6277), and solute carrier family 6 member 3 (SLC6A3) human
      dopamine transporter (hDAT) A559V (rs28364997) single-nucleotide polymorphisms.
      In a case-control study, serum level of HVA, DRD2 C957T, and DAT A559V were
      compared between 85 children who stuttered (CWS) and 85 age- and sex-matched
      children who did not stutter (CWNS). Although serum level of HVA was higher among
      the CWS (median = 25.50 ng/mL) than that in the CWNS (median = 17.40 ng/mL), the
      difference between the two groups was not significant (p = 0.43). No significant
      correlation was observed between age and the level of HVA among all the
      participants (r = -0.15, p = 0.06), nor was there any correlation among the CWS
      (r = -0.19, p = 0.14) or among the CWNS (r = -0.13, p = 0.27) according to the
      Spearman correlation coefficient. On the other hand, there was a significant
      negative correlation between age from stuttering onset and the serum level of HVA
      among the CWS group (r = -0.32, p = 0.01). The Spearman correlation coefficient
      did not indicate any significant correlation between stuttering severity and HVA
      in CWS (r = -0.06, p = 0.59). The mutant allele of hDAT A559V was observed
      neither in the CWS nor in the controls. The allele frequencies of DRD2 C957T were
      not significantly different between the CWS and the CWNS; however, the frequency
      of the TT genotype was significantly higher among the CWS (p = 0.02), which was
      associated with 2.25-fold susceptibility to stuttering (OR = 2.25, 95% CI = 1.03
      to 4.90, p = 0.04). Our findings suggest that the serum level of HVA might be a
      biomarker for dopaminergic involvement in the pathogenesis of stuttering.
      Moreover, the present study indicates that the DRD2 C957T polymorphism might be a
      risk factor for the development of stuttering among Iranian Kurdish population.

PMID- 30199749
TI  - Method validation for simultaneous determination of atropine, pralidoxime and 12
      organophosphorus compounds in blood samples by means of high-performance liquid
      chromatography coupled with tandem mass spectrometry (LC-MS/MS).

PMID- 30199751
TI  - Consultation-liaison psychiatry and physician-assisted death.
AB  - OBJECTIVE: Consultation-liaison (C-L) psychiatrists are involved in physician
      assisted death (PAD) teams in many permitting jurisdictions. This paper will
      describe our Canadian PAD experience over 2 years, highlighting the role of C-L
      psychiatrists, at a large hospital network that provides medical assistance in
      dying (MAID, as this is called in Canada). METHODS: We will describe the Canadian
      criteria for MAID, our multispecialty MAID team experience and the roles, issues
      and concerns experienced by C-L psychiatrists. Some brief patient examples will
      be provided. RESULTS: Our MAID team has managed 186 MAID inquiries, assessed 95
      MAID requests and provided 49 MAID interventions over a 24 month period. The 2 co
      leaders of the MAID team, 8 assessors and 1 intervention physician are C-L
      psychiatrists. Each of the MAID criteria: grievous medical condition, advanced
      state of irreversible decline, intolerable suffering, natural death reasonably
      foreseeable, voluntary request, capacity and informed consent pose specific
      challenges to be resolved in the assessment. Several unique MAID issues,
      including the role of education and mandatory psychiatric assessment and
      protocols will also be discussed. CONCLUSIONS: Our experience shows that C-L
      psychiatrists are well-situated to provide vital expertise and leadership to
      multispecialty PAD teams.

PMID- 30199748
TI  - A simple, sensitive and reliable LC-MS/MS method for the determination of 7-bromo
      5-chloroquinolin-8-ol (CLBQ14), a potent and selective inhibitor of methionine
      aminopeptidases: Application to pharmacokinetic studies.
AB  - CLBQ14 is an 8-hydroxyquinoline analogue that inhibits methionine aminopeptidase
      (MetAP), an enzyme responsible for the post-translational modification of several
      proteins and polypeptides. MetAP has been validated as druggable target for some
      infectious diseases, and its inhibitors have been investigated as potential
      therapeutic agents. In this study, we developed and validated a liquid
      chromatography tandem-mass spectrometry (LC-MS/MS) method for the quantification
      of CLBQ14 in solution, and in rat plasma and urine. This method was applied to
      the pharmacokinetic evaluation of CLBQ14 in adult male Sprague Dawley (SD) rats.
      Chromatographic separation was achieved using an ultra-high-performance liquid
      chromatography (UHPLC) system equipped with Waters XTerra MS C18 column (3.5 MUm,
      125 A, 2.1 * 50 mm) using 0.1% formic acid in acetonitrile/water gradient system
      as mobile phase. Chromatographic analysis was performed with a 4000 QTRAP(r) mass
      spectrometer using MRM in positive mode for CLBQ14 transition [M + H]+m/z 257.919
      -> m/z 151.005, and IS (clioquinol) transition [M + H]+m/z 305.783 -> m/z
      178.917. CLBQ14 was extracted from plasma and urine samples by protein
      precipitation. The retention times for CLBQ14 and IS were 1.31 and 1.40 min
      respectively. The standard curves were linear for CLBQ14 concentration ranging
      from 1 to 1000 ng/mL. The intra-day and inter-day accuracy and precision were
      found to be within 15% of the nominal concentration. Extraction recoveries were
      >96.3% and 96.6% from rat plasma and urine respectively, and there was no
      significant matrix effect from the biological matrices. CLBQ14 is stable in
      samples subjected to expected storage, preparation, and handling conditions.
      Pharmacokinetic studies revealed that CLBQ14 has a bi-exponential disposition in
      SD rats, is extensively distributed with a long plasma half-life and is
      eliminated primarily by liver metabolism.

PMID- 30199752
TI  - hCD46 receptor is not required for measles vaccine Schwarz strain replication in
      vivo: Type-I IFN is the species barrier in mice.
AB  - Measles virus has been successfully attenuated on chicken embryo cells to obtain
      a highly efficient and safe live attenuated vaccine, administered thus far to
      billions of children. Measles virus attenuation has long been described to
      involve a modification of cellular tropism with the use of human CD46 ubiquitous
      receptor. Nevertheless, the use of this receptor in vivo is not obvious. In this
      study we use four different mouse models to decipher the respective part of hCD46
      receptor and type-I interferon response in measles host restriction. We observed
      that only type-I interferon restricts viral replication of attenuated MV Schwarz
      strain in mice, independently of the presence of hCD46 receptor. By comparing
      measles virus immunogenicity in the different models, we confirmed that there was
      no impact on the absence of this receptor on the immune response. Therefore, we
      propose to simplify the mouse model.

PMID- 30199753
TI  - Description and initial characterization of metatranscriptomic nidovirus-like
      genomes from the proposed new family Abyssoviridae, and from a sister group to
      the Coronavirinae, the proposed genus Alphaletovirus.
AB  - Transcriptomics has the potential to discover new RNA virus genomes by sequencing
      total intracellular RNA pools. In this study, we have searched publicly available
      transcriptomes for sequences similar to viruses of the Nidovirales order. We
      report two potential nidovirus genomes, a highly divergent 35.9 kb likely
      complete genome from the California sea hare Aplysia californica, which we assign
      to a nidovirus named Aplysia abyssovirus 1 (AAbV), and a coronavirus-like 22.3 kb
      partial genome from the ornamented pygmy frog Microhyla fissipes, which we assign
      to a nidovirus named Microhyla alphaletovirus 1 (MLeV). AAbV was shown to encode
      a functional main proteinase, and a translational readthrough signal.
      Phylogenetic analysis suggested that AAbV represents a new family, proposed here
      as Abyssoviridae. MLeV represents a sister group to the other known
      coronaviruses. The importance of MLeV and AAbV for understanding nidovirus
      evolution, and the origin of terrestrial nidoviruses are discussed.

PMID- 30199755
TI  - Effects of weak static magnetic fields on the gene expression of seedlings of
      Arabidopsis thaliana.
AB  - Magnetic-field reception of animals and plants is currently discussed in the
      framework of a cryptochrome-based radical-pair mechanism. Efforts to unravel
      magnetoreception in plants suffered historically from several shortcomings, most
      prominently, the conspicuous absence of detailed stimulus-response relationships.
      To determine the sensitivity of seedlings of Arabidopsis thaliana to weak static
      magnetic fields we generated stimulus-response curves between near zero and 188
      MUT for the transcript levels of the genes rbcl, cab4, pal4 and ef1. The moderate
      magneto-responsiveness of dark-grown seedlings was greatly enhanced under blue
      light, and for rbcl and pal4 also under red light. The stimulus-response curves
      obtained under blue light of constant photon-fluence rate displayed multiple
      maxima and thus a pattern fundamentally different from that prevalent in plant
      and animal physiology. A double mutant lacking cryptochromes 1 and 2 displayed
      altered stimulus-response curves without losing, however, magneto-responsiveness
      completely. A reversal of the magnetic field direction substantially affected the
      gene expression and the quantity of CAB-protein (chlorophyll a,b-binding
      protein). The majority of our results are at variance with the notion of
      cryptochromes acting as the only magnetic-field sensors. They do not, however,
      exclude the possibility that cryptochromes participate in the magnetic field
      reception of Arabidopsis. The findings have the unexpected implication that
      cryptochrome- and phytochrome-mediated plant responses can be modulated by the
      strength and the orientation of the local geomagnetic field.

PMID- 30199754
TI  - Virus-like particles presenting flagellin exhibit unique adjuvant effects on
      eliciting T helper type 1 humoral and cellular immune responses to poor
      immunogenic influenza virus M2e protein vaccine.
AB  - Current licensed adjuvants including aluminum hydroxide (alum) bias immune
      responses toward T helper type 2 (Th2) immune responses. We tested whether virus
      like particles presenting flagellin (Flag VLP) exhibit adjuvant effects on
      eliciting Th1 type immune responses and improving the efficacy of poor
      immunogenic tandem repeat M2e (M2e5x) protein vaccine against influenza virus. Co
      immunization of mice with Flag VLP and M2e5x protein vaccine induced
      significantly higher levels of IgG2a isotype (Th1) antibodies in sera and mucosal
      sites, effector CD4+ T cells secreting IFN-gamma and granzyme B, and more
      effective lung viral clearance and protection compared to alum adjuvant. Flag VLP
      stimulated primary macrophages and dendritic cells to secrete inflammatory
      cytokines, which is partially dependent on the Toll-like receptor 5. This study
      provides insight into developing effective vaccine adjuvants.

PMID- 30199758
TI  - Placental peptides regulating islet adaptation to pregnancy: clinical potential
      in gestational diabetes mellitus.
AB  - Pregnancy involves a progressive increase in insulin resistance and the beta
      cells must adapt to compensate and prevent gestational diabetes (GDM). In this
      review we discuss the evidence for placental peptides, including placental
      lactogen, hepatocyte growth factor, adiponectin and leptin, playing a role in the
      islet adaptation to pregnancy. The difficulties of translating data from rodent
      models into human pregnancy are covered and we summarise studies investigating
      associations between serum placental peptides and GDM risk. In conclusion,
      current data support important roles for placental peptides interacting to
      support beta-cells during pregnancy, however mechanisms involved in humans are
      unclear. Further work in humans is required, but placental peptides have clinical
      potential from both a diagnostic and therapeutic perspective.

PMID- 30199757
TI  - Statistical learning and spelling: Evidence from Brazilian prephonological
      spellers.
AB  - We analyzed the spelling attempts of Brazilian children (age 3 years, 3 months to
      6 years, 0 months) who were prephonological spellers, in that they wrote using
      letters that did not reflect the phonemes in the words they were asked to spell.
      We tested the hypothesis that children use their statistical-learning skills to
      learn about the appearance of writing and that older prephonological spellers,
      who have had on average more exposure to writing, produce more wordlike spellings
      than younger prephonological spellers. We found that older prephonological
      spellers produced longer spellings and were more likely to use letters and
      digrams in proportion to their frequency of occurrence in Portuguese. There were
      also some age-related differences in children's tendency to use letters from
      their own names when writing other words. The results extend previous findings
      with learners of English to children who are learning a more transparent
      orthography.

PMID- 30199759
TI  - A Japanese CADASIL patient with homozygous NOTCH3 p.Arg544Cys mutation confirmed
      pathologically.

PMID- 30199760
TI  - Developmental differences in the neural oscillations underlying auditory sentence
      processing in children and adults.
AB  - Although very young children seem to process ongoing language quickly and
      effortlessly, neuroimaging and behavioral studies reveal that children continue
      to mature in their language skills through adolescence. During this prolonged
      development, children likely engage the same basic cognitive processes and neural
      mechanisms to perform language tasks as adults, but in somewhat different ways.
      In this study we used time frequency analysis of EEG to identify developmental
      differences in the engagement of neural oscillations between children (ages 10
      12) and adults while listening to naturally-paced sentences. Adults displayed
      consistent beta changes throughout the sentence compared to children, thought to
      be related to efficient syntactic integration, and children displayed more
      broadly distributed theta changes than adults, thought to be related to more
      effortful semantic integration. Few differences in alpha, related to verbal
      working memory, existed between groups. These findings shed new light on
      developmental changes in the neuronal processes underlying language
      comprehension.

PMID- 30199761
TI  - A Systematic Review of Women's Knowledge of Screening Mammography.
AB  - In light of the contention surrounding the benefit-to-harm ratio of screening
      mammography, this systematic review aimed to understand women's knowledge of
      screening mammography. The search yielded 35 studies of varying methodologies,
      published/completed between 1992 and 2017. Data was collected between November
      2017 and February 2018 and utilised publications from member countries of the
      International Cancer Screening Network- Breast Cancer Division. Data was analysed
      using a narrative synthesis. The results of the review suggest that most women
      are aware of mammograms, however there was large variability regarding the
      awareness of false positives/negatives and about the purpose of screening. Some
      topics (e.g. radiation, commencement age) are well understood by women; however,
      others are not (e.g., cessation age, overdiagnosis, and mortality reduction). The
      findings need to be considered in light of the variability of methods used to
      assess women's knowledge and there is a need to develop psychometrically
      validated and culturally appropriate measures of knowledge regarding screening
      mammography. Further, the lack of consensus regarding what women 'should' know in
      order to provide informed consent has implications for understanding what
      informed consent in breast screening means in practice.

PMID- 30199756
TI  - CRAC channel-based optogenetics.
AB  - Store-operated Ca2+ entry (SOCE) constitutes a major Ca2+ influx pathway in
      mammals to regulate a myriad of physiological processes, including muscle
      contraction, synaptic transmission, gene expression, and metabolism. In non
      excitable cells, the Ca2+ release-activated Ca2+ (CRAC) channel, composed of ORAI
      and stromal interaction molecules (STIM), constitutes a prototypical example of
      SOCE to mediate Ca2+ entry at specialized membrane contact sites (MCSs) between
      the endoplasmic reticulum (ER) and the plasma membrane (PM). The key steps of
      SOCE activation include the oligomerization of the luminal domain of the ER
      resident Ca2+ sensor STIM1 upon Ca2+ store depletion, subsequent signal
      propagation toward the cytoplasmic domain to trigger a conformational switch and
      overcome the intramolecular autoinhibition, and ultimate exposure of the minimal
      ORAI-activating domain to directly engage and gate ORAI channels in the plasma
      membrane. This exquisitely coordinated cellular event is also facilitated by the
      C-terminal polybasic domain of STIM1, which physically associates with negatively
      charged phosphoinositides embedded in the inner leaflet of the PM to enable
      efficient translocation of STIM1 into ER-PM MCSs. Here, we present recent
      progress in recapitulating STIM1-mediated SOCE activation by engineering CRAC
      channels with optogenetic approaches. These STIM1-based optogenetic tools make it
      possible to not only mechanistically recapture the key molecular steps of SOCE
      activation, but also remotely and reversibly control Ca2+-dependent cellular
      processes, inter-organellar tethering at MCSs, and transcriptional reprogramming
      when combined with CRISPR/Cas9-based genome-editing tools.

PMID- 30199763
TI  - Lotus leaf-inspired design of calcium alginate particles with superhigh drug
      encapsulation efficiency and pH responsive release.
AB  - Drug delivery systems with high drug encapsulation efficiency and controlled
      release are of great importance in biomedical fields. Herein, we report an
      ingenious approach inspired from the lotus leaf possessing the ability of strong
      repellency to water, which enables the rapid fabrication of drug-loaded calcium
      alginate (Ca-Alg) particles with high drug encapsulation efficiency and
      controlled drug delivery. The design is achieved by introducing aqueous droplets
      containing the mixture of dilute sodium alginate solution, dilute calcium
      chloride solution, and drug onto the superhydrophobic substrate. Due to water
      evaporation both the concentration of sodium alginate and calcium chloride within
      the droplets will gradually increase, and the ionic crosslinking reaction of
      sodium alginate with Ca2+ is further occurred to form the drug-embedded Ca-Alg
      hydrogel particles. The results indicate that the controllable fabrication of Ca
      Alg particles can be easily achieved on the superhydrophobic surface, and the
      swelling behavior can be tuned by the pH of the buffer solution. Importantly, the
      drug encapsulation efficiencies are measured to be over 88% and the drug exhibits
      obvious pH responsive release. Findings from this study are expected to
      contribute to the rational design of drug delivery systems with high drug
      encapsulation efficiency and controlled release for pharmaceutic science and
      tissue engineering.

PMID- 30199762
TI  - Uptake, depuration, dose estimation and effects in zebrafish exposed to Am-241
      via dietary route.
AB  - Zebrafish were chronically exposed to Am-241, an alpha-emitting radionuclide via
      daily consumption of an enriched artificial diet. Am-241 uptake was quantified in
      Danio rerio after 5 and 21 days of exposure via daily Am-spiked food ingestion
      and after 21 days of exposure followed by 5 days of depuration. Americium
      accumulates mostly in digestive tract, muscle, rest of the body but the
      accumulation levels and trophic transfer rate (0.033-0.013%) were low.
      Corresponding cumulative doses were calculated for the whole body (9 mGy) and for
      the digestive tract (42 mGy) with internal alpha radiation contributing to more
      than 99% of the total dose. Genotoxic effects (gamma-H2AX assay) and differential
      gene expressions of main biological functions were examined. Although fish were
      exposed to a low dose rate of 13 MUGy h-1, DNA integrity and gene expression
      linked to oxidative stress, hormonal signaling and spermatogenesis were altered
      after 21 days of Am-241 exposure. These results underline the higher toxicity of
      alpha emitter Am-241, as compared to other studies on gamma radiation exposure.

PMID- 30199765
TI  - Influence of modified silica nanoparticles on phase behavior and structure
      properties of DPPC monolayers.
AB  - In this work, the effect of silica nanoparticles (NPs) adding to DPPC monolayer
      and the interaction between DPPC and silica nanoparticles are studied. Silica
      nanoparticles are prepared by microemulsion, meanwhile, DMDCS and APTES are used
      to modify silica NPs to get three types of modified silica NPs. These samples are
      mixed with DPPC to form mixed monolayer. By using the atomic force microscope
      (AFM), surface pressure-area and pressure-time isotherms, the effects of
      different hydrophilic-hydrophobic silica nanoparticles on the interface of lipid
      monolayer is analyzed. The data shows that the addition of silica nanoparticles
      changes the phase behavior, the collapse time and the structure of monolayer.
      Hydrophilic silica NPs decreases the collapse pressure and rigidity of DPPC
      monolayer, and makes monolayer collapse earlier since the steric hindrance leads
      to the resistance to compression, while hydrophobic silica NPs have less effect
      on monolayer in collapse pressure or rigidity but the texture of monolayer, and
      the addition of hydrophobic NPs causes the appearance of holes in the monolayer.
      We suppose that there are several possible locations of hydrophobic and
      hydrophilic silica nanoparticles in the air-water interface, which leads to
      different effects on the structure and rheological behavior of monolayer. This
      study can deepen the understanding on how nanoparticles affect human body since
      industries of nanoparticles on drug delivery, oil recovery and floatation are
      developing rapidly and getting more and more outside interest on a daily basis.

PMID- 30199764
TI  - Cellulose acetate - essential oil nanocapsules with antimicrobial activity for
      biomedical applications.
AB  - This study aimed to obtain bioactive nanosystems by combining cellulose acetate
      with three selected essential oils (EOs) to create spherical nanocapsules (NCs)
      using the solvent/anti-solvent technique. The biological activity of the obtained
      NCs was promoted by the use of some antimicrobial EOs: Peppermint, Cinnamon and
      lemongrass which were grafted on the cellulose acetate molecules. Due to their
      chemistry, such as long hydrocarbon tails and heads with functional groups these
      EOs were playing also the role of surfactant-like substance facilitating the
      formation of NCs. A dispersion of NCs was obtained in water and various
      spectroscopy techniques used to examine their size, morphology and chemistry.
      Dynamic light scattering calculate the size of the NCs whereas scanning electron
      microscopy showed their morphology. Fluorescent microscopy and Raman spectroscopy
      proved the attachment of the EOs in the cellulose acetate molecules. The
      antimicrobial activity of the obtained nanomaterials was tested against four
      microbial strains (bacteria: Staphylococcus aureus, Pseudomonas aeruginosa,
      Escherichia coli, and a yeast strain of Candida albicans). The obtained results
      demonstrated that such NCs can be used in a variety of applications including
      medical, pharmaceutical recipients and in household products for treating or
      preventing microbial colonization and biofilm development.

PMID- 30199766
TI  - Lack of chemokine (C-C motif) ligand 3 leads to decreased survival and reduced
      immune response after bacterial meningitis.
AB  - Pneumococcal meningitis, caused by Streptococcus pneumoniae, is the most common
      type of bacterial meningitis. The clinical management of this disease has been
      challenged by the emergence of multidrug-resistant Streptococcus pneumoniae,
      requiring the urgent development of new therapeutic alternatives. Over the course
      of bacterial meningitis, pathogen invasion is accompanied by a massive
      recruitment of peripheral immune cells, especially neutrophil granulocytes, which
      are recruited under the coordination of several cytokines and chemokines. Here,
      we used chemokine (C-C motif) ligand 3 (Ccl3)-deficient mice to investigate the
      functional role of CCL3 in a mouse model of pneumococcal meningitis. Following
      intrathecal infection with Streptococcus pneumoniae Ccl3-deficient mice presented
      a significantly shorter survival and higher bacterial load than wildtype mice,
      paralleled by an ameliorated infiltration of neutrophil granulocytes into the
      CNS. Blood sample analysis revealed that infected Ccl3-deficient mice showed a
      significant decrease in erythrocytes, hemoglobin and hematocrit as well as in the
      number of banded neutrophils. Moreover, infected Ccl3-deficient mice showed an
      altered cytokine expression profile. Glial cell activation remained unchanged in
      both genotypes. In summary, this study demonstrates that CCL3 is beneficial in
      Streptococcus pneumoniae-induced meningitis. Pharmacological modulation of the
      CCL3 pathways might, therefore, represent a future therapeutic option to manage
      Streptococcus pneumoniae meningitis.

PMID- 30199767
TI  - In situ inflammasome activation results in severe damage to the central nervous
      system in fatal Zika virus microcephaly cases.
AB  - Zika virus (ZIKV) has caused substantial concern worldwide owing to its
      association with severe birth defects, such as microcephaly and other congenital
      malformations. Inflammasomes, i.e., multi-protein complexes that induce
      inflammation and pyroptosis, are predicted to contribute to the immune response
      to this flavivirus. Accordingly, in this study, the in situ inflammasome response
      was evaluated in fatal cases of ZIKV-linked microcephaly. Brain tissue samples
      were collected from eight babies, including four ZIKV-positive microcephalic
      neonates who died after birth and four flavivirus-negative neonatal controls who
      died of other causes and whose central nervous system (CNS) architecture was
      preserved. In the ZIKV-positive newborn/stillbirth babies, the major
      histopathological alterations included atrophy of the cortical layer, a
      predominance of mononuclear cell infiltration in the Virchow-Robin space,
      neuronal necrosis, vacuolization and neuronal degeneration, neuronophagy, and
      gliosis. An immunohistochemical analysis of tissues in the neural parenchyma
      showed significantly higher expression of the receptors NLRP1, NLRP3, and AIM2,
      cytokines IL-1beta, IL-18, and IL-33, and enzymes caspase 1, iNOS, and arginase 1
      in ZIKV-positive microcephaly cases than in flavivirus-negative controls. These
      results suggest that inflammasome activation can aggravate the neuroinflammatory
      response and consequently increase CNS damage in neonates with fetal neural ZIKV
      infection and microcephaly.

PMID- 30199768
TI  - Treatment effectiveness and tolerability of afatinib at different doses in
      patients with EGFR-mutated lung adenocarcinoma: How low can we go?
AB  - INTRODUCTION: Afatinib is commonly used as the first-line treatment for EGFR
      mutated lung adenocarcinoma. However, dose adjustments are frequently required.
      This study aimed to investigate the treatment effectiveness of afatinib
      administered at different doses to patients with EGFR-mutated lung
      adenocarcinoma. METHODS: Treatment-naive patients with advanced EGFR-mutated lung
      adenocarcinoma who received afatinib therapy between May 2014 and September 2016
      were enrolled retrospectively. Collected clinical data included age, sex, smoking
      history, performance status, disease stages, EGFR mutation status, initial doses
      of afatinib, dose adjustments, treatment responses, progression-free survival and
      treatment-associated adverse events. The average daily dose was calculated by
      dividing the summation of all doses of prescribed tablets during the treatment
      period by the total days of afatinib use. The patients were classified into five
      treatment groups based on average daily doses: 40 mg, <40 and >30 mg, 30 mg, <30
      and >= 20 mg and <20 mg. RESULTS: A total of 254 patients were included. No
      significant differences were found among these five treatment groups with respect
      to response rates (69.3%, 68.3%, 70.5%, 77.8% and 66.7%, respectively, p = 0.920)
      and disease control rates (97.4%, 95.2%, 97.7%, 100% and 100%, respectively, p =
      0.749). However, the treatment group with an average daily dose of <20 mg had a
      significant shorter progression-free survival as compared with the other groups
      (16.8, 12.4, 13.9, 17.0 and 5.3 months, respectively, p = 0.049). CONCLUSIONS:
      Dose reduction may not affect the treatment effectiveness until the average daily
      dose is below 20 mg. Further prospective studies of afatinib therapy at different
      daily doses are warranted.

PMID- 30199769
TI  - Cross-correlation between spine and hip joint kinematics differs in healthy
      individuals and subgroups of ankylosing spondylitis patients during trunk lateral
      flexion.
AB  - BACKGROUND: The effects of sacroiliitis and syndesmophyte formation on the cross
      correlation between spine and hip joint kinematics in ankylosing spondylitis (AS)
      are poorly understood. OBJECTIVE: To investigate the cross-correlation between
      spine and hip joint kinematics differs in healthy individuals and ankylosing
      spondylitis patients during trunk lateral flexion. METHODS: Fifty AS patients and
      thirty-nine healthy adults (controls) were recruited from a medical center. The
      patients were divided into two subgroups, namely the sacroiliitis (n = 28) and
      syndesmophyte (n = 22) subgroups. An inertial motion system was used to record
      kinematic data of spine, pelvic and hip joints during lateral trunk flexion. The
      maximal cross-correlation coefficient (CCF) and time lag of motion between the
      spine and hip joint were analyzed. RESULTS: The syndesmophyte group had the
      smallest range of motion in all recorded motion. The sacroiliitis group exhibited
      higher thoracic flexion, pelvic pitch, and pelvic rotation than the other two
      groups. In the syndesmophyte group, the CCF between lumbar lateral flexion (LLF)
      and hip abduction were weakly and LLF and hip rotation were strongly correlated.
      Considering in time sequence, LLF occurred earlier than hip abduction and hip
      rotation during trunk lateral flexion; however, both AS subgroups exhibited
      longer time lags than in the control group. CONCLUSION: The cross-correlation
      between spine and hip joint kinematics differs in healthy individuals and AS
      patients during trunk lateral flexion. The motion pattern changes in patients
      with AS of differing severity may also alter the loads on the spine and hip
      joints.

PMID- 30199770
TI  - Paranormal belief, thinking style preference and susceptibility to confirmatory
      conjunction errors.
AB  - This study examines the extent to which belief in extrasensory perception (ESP),
      psychokinesis (PK) or life after death (LAD), plus need for cognition (NFC) and
      faith in intuition (FI), predict the generation of confirmatory conjunction
      errors. An opportunity sample (n = 261) completed sixteen conjunction problems
      manipulated across a 2 event type (paranormal vs. non-paranormal) * 2 outcome
      type (confirmatory vs. disconfirmatory) within subjects design. Three Generalised
      Linear Mixed Models - one per paranormal belief type - were performed. With
      respondent gender and age controlled for, ESP, PK and LAD beliefs were all
      associated with the making (vs. non-making) of conjunction errors both generally
      and specifically for confirmatory conjunctive outcomes. Event type had no impact.
      Individuals high in NFC were less likely to commit the fallacy. The role thinking
      style plays in shaping paranormal believers' susceptibility to confirmatory
      conjunction biases is discussed. Methodological issues and future research ideas
      are also considered.

PMID- 30199771
TI  - A preliminary trial of an online dissonance-based eating disorder intervention.
AB  - OBJECTIVE: We conducted a controlled randomized preliminary trial of an expanded
      online version of the Body Project (n = 46) compared to an assessment-only
      control condition (n = 36) via a longitudinal design (baseline, postintervention,
      2-month follow-up) in a community sample of women (N = 82) with clinical (n = 53)
      and subclinical (n = 29) eating disorder symptoms. METHOD: The traditional
      content of the Body Project was modified to include verbal, written, and
      behavioral exercises designed to dissuade objectification and maladaptive social
      comparison and adapted to an online format. Body dissatisfaction, self-esteem,
      self-objectification, thin-ideal internalization, maladaptive social comparison,
      trait anxiety, positive affect, negative affect, and eating disorder
      symptomatology were evaluated in the control and the online expanded Body Project
      condition at baseline, postintervention, and 2-month follow-up. RESULTS: A 2
      (condition: online expanded Body Project, control) * 3 (time: baseline,
      postintervention, 2-month follow-up) mixed factorial multivariate analysis of
      variance (MANOVA) was conducted to examine statistically significant group
      differences. As predicted, results indicated a statistically significant
      condition * time interaction. CONCLUSIONS: Participants in the expanded online
      Body Project condition showed significant reductions in eating disorder symptoms
      and several associated psychological risk correlates from baseline to
      postintervention and follow-up; contrary to predictions, eating disorder symptoms
      and risk correlates were not significantly lower in the online expanded Body
      Project condition compared to the waitlist control condition at postintervention
      or 2-month follow-up.

PMID- 30199773
TI  - Heat exposure during outdoor activities in the US varies significantly by city,
      demography, and activity.
AB  - Environmental heat is a growing public health concern in cities. Urbanization and
      global climate change threaten to exacerbate heat as an already significant
      environmental cause of human morbidity and mortality. Despite increasing risk,
      very little is known regarding determinants of outdoor urban heat exposure. To
      provide additional evidence for building community and national-scale resilience
      to extreme heat, we assess how US outdoor urban heat exposure varies by city,
      demography, and activity. We estimate outdoor urban heat exposure by pairing
      individual-level data from the American Time Use Survey (2004-2015) with
      corresponding meteorological data for 50 of the largest metropolitan statistical
      areas in the US. We also assess the intersection of activity intensity and heat
      exposure by pairing metabolic intensities with individual-level time-use data. We
      model an empirical relationship between demographic indicators and daily heat
      exposure with controls for spatiotemporal factors. We find higher outdoor heat
      exposure among the elderly and low-income individuals, and lower outdoor heat
      exposure in females, young adults, and those identifying as Black race.
      Traveling, lawn and garden care, and recreation are the most common outdoor
      activities to contribute to heat exposure. We also find individuals in cities
      with the most extreme temperatures do not necessarily have the highest outdoor
      heat exposure. The findings reveal large contrasts in outdoor heat exposure
      between different cities, demographic groups, and activities. Resolving the
      interplay between exposure, sensitivity, adaptive capacity, and behavior as
      determinants of heat-health risk will require advances in observational and
      modeling tools, especially at the individual scale.

PMID- 30199772
TI  - Differential effect of multiple kinesin motors on run length, force and
      microtubule binding rate.
AB  - The in vitro transport of cargo by motor proteins constitutes a model system to
      understand mechanisms of vesicle trafficking inside cells. Here we apply the
      classic bead assay with a short, stiff kinesin protein to test the effect of
      multiple motors on essential transport parameters: distance, force and
      microtubule binding rate. Measurements of unloaded run length show that the
      transition from single- to multiple-motor behavior can be characterized by the
      appearance of extended runs, in accordance with a recently proposed model that
      quantifies the probability of multiple-motor engagement. In this transition,
      application of mechanical load using optical tweezers allows us to register
      maximum force values above single kinesin levels (8 pN). Yet, averages of run
      length and maximum force undergo little change as the probability of multiple
      motor participation increases. In contrast, the measured rate of bead binding to
      microtubules scales linearly with the average number of motors per bead. These
      observations suggest that multiple motors bound randomly to the same cargo mainly
      increase the probability of attachment of these cargoes to the cytoskeletal
      filament network.

PMID- 30199774
TI  - The chemical and dynamic distribution characteristics of iron, cobalt and nickel
      in three different anaerobic digestates: Effect of pH and trace elements dosage.
AB  - The enhancement of the bioavailability and process controllability of trace
      elements (TEs) addition is of significance to improve the anaerobic digestion
      (AD) performance. In order to understand the bioavailability of TEs, the chemical
      form distribution patterns of endogenous/exogenous Fe, Ni and Co with different
      dosage (Fe: 1, 10 and 100 mg/kg; Ni and Co: 0.1, 1 and 10 mg/kg) and different pH
      condition (6.5; 7.5 and 8.5) were investigated in three different anaerobic
      digestates. The results showed that the exogenous TEs dosage exerted no obvious
      effects on the TEs distribution patterns. The chemical fractionation of TEs was
      more affected by pH, redox potential, AD process and digestate resource. Under pH
      6.5 and with redox potential rising, the acid-extractable and reducible fractions
      and of Fe, Ni and Co were increased while the oxidizable fractions were
      decreased, which enhanced the bioavailability of TEs.

PMID- 30199775
TI  - Optimizing the configuration of integrated nutrient and energy recovery treatment
      trains: A new application of global sensitivity analysis to the generic nutrient
      recovery model (NRM) library.
AB  - This paper describes the use of global sensitivity analysis (GSA) for factor
      prioritization in nutrient recovery model (NRM) applications. The aim was to
      select the most important factors influencing important NRM model outputs such as
      biogas production, digestate composition and pH, ammonium sulfate recovery,
      struvite production, product purity, particle size and density, air and chemical
      requirements, scaling potential, among others. Factors considered for GSA
      involve: 1) input waste stream characteristics, 2) process operational factors,
      and 3) kinetic parameters incorporated in the NRMs. Linear regression analyses on
      Monte Carlo simulation outputs were performed, and the impact of the standardized
      regression coefficients on major performance indicators was evaluated. Finally,
      based on the results, the paper describes the original use of GSA to obtain
      insight in complex nutrient recovery systems and to propose an optimal nutrient
      and energy recovery treatment train configuration that maximizes resource
      recovery and minimizes energy and chemical requirements.

PMID- 30199776
TI  - Opioid misuse and perceived smoking-pain relationships among HIV+ individuals
      with pain: Exploring negative affect responses to pain.
AB  - Persons living with HIV/AIDS (PLWHA) report high rates of clinically significant
      pain that is associated with several negative outcomes, including higher CD4 T
      cell count, poor medication adherence, and substance use and misuse. Importantly,
      PLWHA also report elevated rates of both opioid and tobacco use, and these
      elevated rates have often been associated with increased pain experience.
      Although research suggests that negative affective responses to pain may be
      uniquely associated with substance misuse among individuals in the general
      population, little work has examined these relations among PLWHA. The current
      study examined negative emotions in response to pain as a predictor of current
      opioid misuse, future opioid misuse, and perceived smoking-pain relationships
      among 66 (Mage = 51.26, SD = 8.00, 60.6% male) HIV+ adults with co-occurring
      pain. Results indicated that negative emotions in response to pain uniquely
      predicted each of the substance use outcomes, with clinically significant effect
      sizes that may be characterized as medium in magnitude. Overall, these findings
      suggest that negative affective responses to pain may play a role in prescription
      opioid misuse and smoking among PLWHA. These findings may inform the development
      of tailored interventions for PLWHA smokers who are prescribed opioid pain
      medications.

PMID- 30199777
TI  - Functional behaviour of spinal muscles after training with an exercise device
      developed to recruit and train postural muscles.
AB  - This study investigated the effects of a single exercise session using a device
      developed for postural muscle training on the function of postural muscles in
      healthy, pain free individuals. During standardised rapid arm movements, timing
      of onset of electromyography (EMG) was measured using intramuscular and surface
      recordings of the transversus abdominis (TrA), obliquus internus abdominis (OI),
      obliquus externus abdominis (OE), lumbar multifidus (LM) and lumbar erector
      spinae (LES) muscles. A single exercise session with the device led to
      significantly (main effect of time: P = 0.03) earlier LES EMG onset in advance of
      the postural perturbation induced by rapid forward arm movements from -1 ms (SD:
      32 ms) at baseline to -11 ms (SD: 27 ms) post-exercise and -16 ms (SD: 22 ms) at
      10-min Wash-Out after the FRED exercise bout. The timing of EMG onset of the
      other trunk muscles was not affected by the single bout of exercise. A
      significant correlation was found between background activity and the EMG onset
      times of of TrA (r = 0.6; P < 0.001), OI (r = 0.59; P < 0.001), LES (r = 0.32; P
      = 0.046) and LMs (r = 0.77; P < 0.001). Higher levels of trunk muscle background
      activity were associated with later onset times. The present findings suggest
      that a single exposure to the postural training device can induce small changes
      in spinal muscle function in healthy pain free individuals.

PMID- 30199779
TI  - Reliability of joint kinematic calculations based on direct kinematic and inverse
      kinematic models in obese children.
AB  - BACKGROUND: In recent years, the reliability of inverse (IK) and direct kinematic
      (DK) models in gait analysis have been assessed intensively, but mainly for lean
      populations. However, obesity is a growing issue. So far, the sparse results
      available for the reliability of clinical gait analysis in obese populations are
      limited to direct kinematic models. Reliability error-margins for inverse
      kinematic models in obese populations have not been reported yet. RESEARCH
      QUESTIONS: Is there a difference in the reliability of IK models compared with a
      DK model in obese children? Are there any differences in the joint kinematic
      output between IK and DK models? METHODS: A test-retest study was conducted using
      three-dimensional gait analysis data from two obese female and eight obese male
      participants from an earlier study. Data were analyzed using a DK model and two
      OpenSim-based IK models. Test-retest reliability was compared by calculating the
      Standard Error of Measurement (SEM) along with similar absolute reliability
      measures. A Friedman Test was used to assess whether there were any significant
      differences in the reliability between the models. Kinematic output of the models
      was compared by using Statistical Parametric Mapping (SPM). RESULTS: No
      significant differences were found in the reliability between the DK and IK
      models. The SPM analysis indicated several significant differences between both
      IK models and the DK approach. Most of these differences were continuous offsets.
      SIGNIFICANCE: Reliability values showed clinically acceptable error-margins and
      were comparable between all models. Therefore, our results support the careful
      use of IK models in overweight or obese populations, e.g. for musculoskeletal
      modelling studies. The inconsistent kinematic output can mainly be explained by
      different model conventions and anatomical segment coordinate frame definitions.

PMID- 30199778
TI  - Pre-operative sensor-based gait parameters predict functional outcome after total
      knee arthroplasty.
AB  - BACKGROUND: Despite the general success of total knee arthroplasty (TKA)
      regarding patient-reported outcome measures, studies investigating gait function
      have shown diverse functional outcomes. Mobile sensor-based systems have recently
      been employed for accurate clinical gait assessments, as they allow a better
      integration of gait analysis into clinical routines as compared to laboratory
      based systems. RESEARCH QUESTION: In this study, we sought to examine whether an
      accurate assessment of gait function of knee osteoarthritis patients with respect
      to surgery outcome evaluation after TKA using a mobile sensor-based gait analysis
      system is possible. METHODS: A foot-worn sensor-based system was used to assess
      spatio-temporal gait parameters of 24 knee osteoarthritis patients one day before
      and one year after TKA, and in comparison to matched control participants.
      Patients were clustered into positive and negative responder groups using a
      heuristic approach regarding improvements in gait function. Machine learning was
      used to predict surgery outcome based on pre-operative gait parameters. RESULTS:
      Gait function differed significantly between controls and patients. Patient
      reported outcome measures improved significantly after surgery, but no
      significant global gait parameter difference was observed between pre- and post
      operative status. However, the responder groups could be correctly predicted with
      an accuracy of up to 89% using pre-operative gait parameters. Patients exhibiting
      high pre-operative gait function were more likely to experience a functional
      decrease after surgery. Important gait parameters for the discrimination were
      stride time and stride length. SIGNIFICANCE: The early identification of post
      surgical functional outcomes of patients is of great importance to better inform
      patients pre-operatively regarding surgery success and to improve post-surgical
      management.

PMID- 30199780
TI  - Pathogenic E. coli HPI upregulate the expression of inflammatory factors in
      porcine small intestinal epithelial cells by ubiquitin proteasome pathway.
AB  - To investigate the effects of pathogenic Escherichia coli high pathogenicity
      island (HPI) on the expression of inflammatory factors via ubiquitin proteasome
      pathway. Firstly, the UBC-sus-263 shRNA plasmid was successfully established and
      transfected into porcine small intestine epithelial cells (IPEC-J2) by liposome
      to silence the ubiquitinntion gene. Then the IPEC-J2 was infected with E. coli
      HPI+ and HPI- strains, respectively. Finally, the mRNA of intracellular NF-kappaB
      and IkappaB-alpha,and the protein levels of NF-kappaB, IkappaB-alpha, TNF-alpha
      and IL-1 in IPEC-J2 cell line transfected with UBC-sus-263 shRNA (Ub-shRNA) were
      detected. The results showed that the Ub-shRNA was effectively inhibited
      ubiquitination pathway in the IPEC-J2 cell. After infected with HPI+, the mRNA
      and protein levels of NF-kappaB and IkappaB-alpha were dramatically decreased in
      Ub-hsRNA transfected IPEC-J2 cells compared to the control and HPI--infected
      groups. Consistently, the production of downstream cytokines such as TNF-alpha
      and IL-1 were highly expressed after HPI+-infection than that of HPI--infected
      groups. However, whether the HPI+ or HPI-, both could induce increasingly
      expression of NF-kappaB and IkappaB-alpha and its downstream cytokines in normal
      IPEC-J2 cells. Thus, the E. coli HPI can upregulate the expression of IkappaB
      alpha to promote the releasing of TNF-alpha and IL-1 via the ubiquitination
      pathway.

PMID- 30199781
TI  - Bipartite synchronization in coupled delayed neural networks under pinning
      control.
AB  - This paper considers the bipartite leader-following synchronization in a signed
      network composed by an array of coupled delayed neural networks by utilizing the
      pinning control strategy and M-matrix theory, where the communication links
      between neighboring nodes of the network can be either positive or negative.
      Under the assumption that the node-delay is bounded and differentiable, a
      sufficient condition in terms of a low-dimensional linear matrix inequality is
      derived for reaching bipartite leader-following synchronization in the signed
      network, based on which a simple algebraic formula is further given to estimate
      an upper bound of the node-delay. When the node-delay is bounded and non
      differentiable, some criteria are established by using the descriptor method and
      the reciprocally convex approach such that the bipartite leader-following
      synchronization problem for the signed network can be successfully solved.
      Finally, numerical simulations are provided to illustrate the effectiveness of
      theoretical analysis.

PMID- 30199782
TI  - Multi-view clustering on unmapped data via constrained non-negative matrix
      factorization.
AB  - Existing multi-view clustering algorithms require that the data is completely or
      partially mapped between each pair of views. However, this requirement could not
      be satisfied in many practical settings. In this paper, we tackle the problem of
      multi-view clustering on unmapped data in the framework of NMF based clustering.
      With the help of inter-view constraints, we define the disagreement between each
      pair of views by the fact that the indicator vectors of two samples from two
      different views should be similar if they belong to the same cluster and
      dissimilar otherwise. The overall objective of our algorithm is to minimize the
      loss function of NMF in each view as well as the disagreement between each pair
      of views. Furthermore, we provide an active inter-view constraints selection
      strategy which tries to query the relationships between samples that are the most
      influential and samples that are the farthest from the existing constraint set.
      Experimental results show that, with a small number of (either randomly selected
      or actively selected) constraints, the proposed algorithm performs well on
      unmapped data, and outperforms the baseline algorithms on partially mapped data
      and completely mapped data.

PMID- 30199783
TI  - Estimation of neural connections from partially observed neural spikes.
AB  - Plasticity is one of the most important properties of the nervous system, which
      enables animals to adjust their behavior to the ever-changing external
      environment. Changes in synaptic efficacy between neurons constitute one of the
      major mechanisms of plasticity. Therefore, estimation of neural connections is
      crucial for investigating information processing in the brain. Although many
      analysis methods have been proposed for this purpose, most of them suffer from
      one or all the following mathematical difficulties: (1) only partially observed
      neural activity is available; (2) correlations can include both direct and
      indirect pseudo-interactions; and (3) biological evidence that a neuron typically
      has only one type of connection (excitatory or inhibitory) should be considered.
      To overcome these difficulties, a novel probabilistic framework for estimating
      neural connections from partially observed spikes is proposed in this paper.
      First, based on the property of a sum of random variables, the proposed method
      estimates the influence of unobserved neurons on observed neurons and extracts
      only the correlations among observed neurons. Second, the relationship between
      pseudo-correlations and target connections is modeled by neural propagation in a
      multiplicative manner. Third, a novel information-theoretic framework is proposed
      for estimating neuron types. The proposed method was validated using spike data
      generated by artificial neural networks. In addition, it was applied to multi
      unit data recorded from the CA1 area of a rat's hippocampus. The results
      confirmed that our estimates are consistent with previous reports. These findings
      indicate that the proposed method is useful for extracting crucial interactions
      in neural signals as well as in other multi-probed point process data.

PMID- 30199784
TI  - Pulmonary embolism in Europe - Burden of illness in relationship to healthcare
      resource utilization and return to work.
AB  - OBJECTIVES: Pulmonary embolism (PE) is associated with a substantial economic
      burden. However evidence from patients in Europe is scarce. The aim of this study
      was to report the impacts of PE on healthcare resource utilization (HCRU) and
      return to work using the PREFER in VTE registry. METHODS: The PREFER in VTE
      registry was a prospective, observational, multicenter study in seven European
      countries, aiming to provide data concerning treatment patterns, HCRU, mortality,
      quality of life and work-loss. Patients with a first-time or recurrent PE were
      included and followed up at 1, 3, 6 and 12 months. Treatment patterns, re
      hospitalization rates, length of hospital stays (LOS), and ambulatory/office
      visits, as well as proportion of patients returning to work, were assessed.
      Subgroups by country and with/without active cancer were examined separately.
      Zero-inflated negative binomial and Cox regression were applied to investigate
      the relationship between baseline characteristics and LOS and return to work,
      respectively. RESULTS: Amongst 1399 patients with PE, 53.2% were male and the
      average age was 62.3 +/- 17.1 years old. Overall, patients were treated with
      combinations of heparin, vitamin K antagonists (VKA) and the non-VKA oral
      anticoagulants (NOACs) (50.0% treated with the combination of heparin with VKA).
      Patients with active cancer were primarily treated with heparin (84.9%). NOACs
      were used more frequently in DACH (Germany, Austria and Switzerland) and France
      (55.2% and 32.6%) compared to Italy and Spain (4.5% and 6.1%). The VTE-related re
      hospitalization rate within 12 months and the average LOS varied substantially
      between countries, from 26.2% in UK to 12.3% in France, and from 12.9 days in
      Italy to 3.9 days in France. PE patients were often co-managed by general
      practitioners in France and DACH (>84%), and less frequently in other countries
      (<47%). The regression results confirmed the country variation of HCRU. Of the
      employed patients (n = 385), 60% returned to work at 1 month but 27.8% had not
      after one year. PE patients with DVT were more likely to return to work. Active
      cancer was a significant predictor for not returning to work, as well as smoking
      history. CONCLUSIONS: Medical treatment of PE differed between patients with
      active cancer and patients without active cancer. VTE-related resource
      utilization differed markedly between countries. While the reported 'not return
      to work' was high for patients with PE, this may at least in part reflect the
      presence of co-morbidities such as cancer.

PMID- 30199785
TI  - Study on antiplatelet effect of a new thiophenopyridine platelets P2Y12 receptor
      antagonist DV-127.
AB  - P2Y12 receptor antagonists are a class of drugs that act on platelet P2Y12
      receptors and inhibit adenosine diphosphate-induced platelet aggregation. As a
      thienopyridine antiplatelet agent which is approved by the US Food and Drug
      Administration for the treatment of cardiovascular diseases, currently,
      clopidogrel was once considered to be the most safe and effective antiplatelet
      drug in the P2Y12 receptor antagonists, however, it has become increasingly clear
      that clopidogrel does not satisfactorily inhibit the platelets of approximately
      one-third of patients. This is in part due to clopidogrel is a prodrug and
      reliance on multiple cytochrome P450 enzymes for conversion into its active
      metabolite. Prasugrel and ticagrelor reduces the risk of adverse cardiovascular
      events compared to clopidogrel in acute coronary syndromes patients, however, the
      cardiovascular benefit of both drugs is counter-balanced by increased rates of
      spontaneous bleeding. Unlike clopidogrel, which is a prodrug, cangrelor is an
      active drug not requiring metabolic conversion, despite fewer bleeding events
      during cardiac surgery, cangrelor carries the risk of potential autoimmune
      reactions manifesting as breathlessness. DV-127 was synthesized by using three
      generations of thienopyridine P2Y12 receptor antagonists as research models,
      using high resolution mass spectrometry, selective deuteration, and 2,7-position
      replacement groups technologies in order to maximize cardiovascular benefit while
      minimizing adverse effects on hemostasis. Our results show that although the dose
      of DV-127 is greatly reduced, it can achieve similar anticoagulant and
      antiplatelet effects as clopidogrel, and DV-127 can more strongly inhibit the
      release of alpha-granules even though the inhibitory effect of dense granules is
      similar to clopidogrel.

PMID- 30199786
TI  - Anti-c-Mpl antibodies in immune thrombocytopenia suppress thrombopoiesis and
      decrease response to rhTPO.
AB  - INTRODUCTION: Anti-TPO receptor (anti-c-Mpl) antibodies exist and could affect
      rhTPO treatment in ITP. MATERIALS AND METHODS: Anti-c-Mpl autoantibodies and TPO
      levels were measured in serum from 187 ITP patients and 59 healthy controls. The
      anti-c-Mpl-antibody-positive (anti-c-Mpl+) and anti-c-Mpl-antibody-negative (anti
      c-Mpl-) IgG from ITP patients were assessed on megakaryocyte proliferation,
      polyploidy, apoptosis, and platelet release with rhTPO treatment. RESULTS: Anti-c
      Mpl antibodies were detected in 54/187 ITP patients but in none of the controls.
      ITP patients with anti-c-Mpl antibodies had higher serum TPO levels, but lower
      megakaryocyte and platelet counts compared with anti-c-Mpl- patients. Antibodies
      targeting platelet glycoprotein (GP) were also more frequently identified in anti
      c-Mpl+ ITP patients. Moreover, patients with anti-c-Mpl antibodies were less
      responsive to rhTPO treatment than patients without anti-c-Mpl antibodies.
      Additionally, the anti-c-Mpl antibody titer decreased in ITP patients following
      treatment. In vitro study, lower megakaryopoiesis, platelet generation and
      percent of polyploidy were observed in anti-c-Mpl+ group compared with the anti-c
      Mpl- group in the presence of rhTPO. CONCLUSIONS: Our findings demonstrated that
      the anti-c-Mpl antibody represents a novel indicator of poor prognosis and may be
      a potential therapeutic target in ITP.

PMID- 30199787
TI  - 5-Benzoyl triazole as new structural dimension in glycoconjugates.
AB  - In recent years, 1,4-triazole rings are being widely used for the synthesis of
      carbohydrate derived biomimetics, due to their easy synthesis and wide range of
      functional group compatibility. These triazole rings lead to synthetic molecules
      with improved enzymatic stability, bioavailability, and structural diversity. In
      this present work, a benzoyl group has been introduced at the C-5 position of the
      triazole ring present in the synthetic glycoconjugates providing further
      structural diversity to the molecule. 5-Benzoyl 1,4-triazole ring containing
      glycoconjugates were synthesized using Cu(I) catalyzed [3 + 2] cycloaddition
      reaction of per-O-acetylated glycopyranosyl azide and phenyl acetylene followed
      by in situ electrophilic addition of benzoyl group to the Cu(I) coordinated
      triazole intermediate. The X-ray crystal structure of one of the 5-benzoyl 1,4
      triazole linked glycoconjugate derived from d-xylose {1-N-(2,3,4-tri-O-acetyl
      beta-d-xylopyranosyl)-4-phenyl-5-benzoyl-1,2,3-triazole} showed unique pattern of
      intermolecular CH...O interactions arranging the molecules in an anti-parallel
      orientation. The structure and morphology of the compounds were further explored
      using computational calculation and scanning electron microscopic (SEM) study
      which firmly established the uniqueness of 5-benzoyl 1,4-triazole linked
      glycoconjugates compared to that of 5-H 1,4-triazole linked derivative.

PMID- 30199788
TI  - Long-distance movement of helical multipartite phytoviruses: keep connected or
      die?
AB  - All living organisms have to preserve genome integrity to ensure the survival of
      progeny generations. Viruses, though often regarded as 'non living', protect
      their nucleic acids from biotic and abiotic stresses, ranging from nuclease
      action to radiation-induced adducts. When the viral genome is split into multiple
      segments, preservation of at least one copy of each segment is required. While
      segmented and monopartite viruses use an all-in-one strategy, multipartite
      viruses have to address in the cell at least one of each viral particle in which
      the split positive stranded RNA genome is individually packaged. Here, we review
      and discuss the biology of multipartite helical RNA phytoviruses to outline our
      current hypothesis on a coordinated genomic RNA network RNP complex that
      preserves an all-in-one strategy and genome integrity.

PMID- 30199790
TI  - Light-induced dipolar spectroscopy - A quantitative comparison between LiDEER and
      LaserIMD.
AB  - Nanometric distance measurements with EPR spectroscopy yield crucial information
      on the structure and interactions of macromolecules in complex systems. The range
      of suitable spin labels for such measurements was recently expanded with a new
      class of light-inducible labels: the triplet state of porphyrins. Importantly,
      accurate distance measurements between a triplet label and a nitroxide have been
      reported with two distinct light-induced spectroscopy techniques, (light-induced)
      triplet-nitroxide DEER (LiDEER) and laser-induced magnetic dipole spectroscopy
      (LaserIMD). In this work, we set out to quantitatively compare the two techniques
      under equivalent conditions at Q band. Since we find that LiDEER using a
      rectangular pump pulse does not reach the high modulation depth that can be
      achieved with LaserIMD, we further explore the possibility of improving the
      LiDEER experiment with chirp inversion pulses. LiDEER employing a broadband pump
      pulse results in a drastic improvement of the modulation depth. The relative
      performance of chirp LiDEER and Laser-IMD in terms of modulation-to-noise ratio
      is found to depend on the dipolar evolution time: While LaserIMD yields higher
      modulation-to-noise ratios than LiDEER at short dipolar evolution times
      (tau=2MUs), the high phase memory time of the triplet spins causes the situation
      to revert at tau=6MUs.

PMID- 30199789
TI  - Differential phosphatidic acid metabolism in barley leaves and roots induced by
      chilling temperature.
AB  - Phosphatidic acid (PA) is an important bioactive lipid that mediates chilling
      responses in barley. Modifications in the lipid composition of cellular membranes
      during chilling are essential to maintain their integrity and fluidity. First, we
      investigated the molecular species of PA present in leaves and roots by ESI
      MS/MS, to evaluate the modifications that occur in response to chilling. We
      demonstrated that PA pools in leaves differ from PA fatty acid composition in
      roots. Compared with plants grown at 25  degrees C, the short-term and long-term
      chilling for 3 h and 36 h at 4  degrees C not produced significant changes in PA
      molecular species. The endogenous DAG and PA phosphorylation by in vitro DAG and
      PA kinase activities showed higher activity in leaves compared with that in root,
      and they showed contrasting responses to chilling. Similarly, PA removal by
      phosphatidate phosphohydrolase was tested, showing that this activity was
      specifically increased in response to chilling in roots. The findings presented
      here may be helpful to understand how the PA signal is modulated between tissues,
      and may serve to highlight the importance of knowing the basal PA pools in
      different plant organs.

PMID- 30199792
TI  - Differential release of sewage sludge biochar-borne elements by common low
      molecular-weight organic acids.
AB  - Biochar materials originated from sewage sludge may contain elevated levels of
      potentially toxic elements. There was a lack of information on the mobility of
      biochar-borne elements, as driven by low-molecular-weight organic acids (LMWOAs)
      contained in plant root exudates. A batch experiment was conducted to examine the
      effects of three common LMWOAs on the release of major elements and trace
      elements with a focus on various potentially toxic trace elements. The results
      showed that substantial amounts of Al, Mn, Fe, K, Na and Mg were extracted from
      two sewage sludge-derived biochar materials by the LMWOAs. A much higher release
      rate of potentially toxic trace elements was observed in the presence of LMWOAs,
      as compared to reported data using extractants not encountered in root exudates.
      The LMWOA-driven releasibility of various potentially toxic trace elements was in
      the following decreasing order: Zn > Ni > Pb > Cu > Cr >Co = Cd. Other trace
      elements that are subject to mobilization in the presence of LMWOAs included B,
      Ba, In, Li and Sr except Ba under oxalic acid extraction. Among the three LMWOAs,
      oxalic acid showed a generally stronger capacity to mobilize these metals. The
      findings obtained from this study provides new information that can be used for
      better evaluating the phyto-availability of trace elements bound to sewage sludge
      originated biochar materials.

PMID- 30199791
TI  - RF atomic magnetometer array with over 40 dB interference suppression using
      electron spin resonance.
AB  - An unshielded array of 87Rb atomic magnetometers, operating close to 1 MHz, is
      used to attenuate interference by 42-48 dB. A sensitivity of 15 fT/Hz to a local
      source of signal is retained. In addition, a 2D spectroscopic technique, in which
      the magnetometers are repeatedly pumped and data acquired between pump times,
      enables a synchronously generated signal to be distinguished from an interfering
      signal very close in frequency; the timing and signal mimics what would be
      observed in a magnetic resonance echo train. Combining the interference rejection
      and the 2D spectroscopy techniques, a 100 fT local signal is differentiated from
      a 20 pT interference signal operating only 1 Hz away. A phase-encoded reference
      signal is used to calibrate the magnetometers in real time in the presence of
      interference. Key to the strong interference rejection is the accurate
      calibration of the reference signal across the array, obtained through electron
      spin resonance measurements. This calibration is found to be sensitive to atomic
      polarization, RF pulse duration, and direction of the excitation. The
      experimental parameters required for an accurate and robust calibration are
      discussed.

PMID- 30199793
TI  - The role of submerged macrophytes in phytoremediation of arsenic from
      contaminated water: A case study on Vallisneria natans (Lour.) Hara.
AB  - Arsenic contamination of water is a global concern due to its heavy threat to
      human health. In this study, the submerged macrophyte Vallisneria natans (Lour.)
      Hara was used to remove environmentally relevant concentrations of arsenic in the
      binary As(III)/As(V) system. The concentrations of total arsenic (tAs) and
      As(III) in water dropped rapidly within 3 days, while As(V) first increased
      slightly within 3 days and then gradually decreased. About 1.2% dimethylarsinate
      (DMA) was detected at the 14th day of treatment. These findings indicated that
      As(III) could be oxidized to As(V) and methylated to DMA in water with V. natans.
      In relation to V. natans, both tAs and As(V) were much higher in roots compared
      to leaves. Arsenate was the predominant species (>= 95.65 +/- 0.10%) in roots,
      and As(III) was only found at the 14th day (3.45-6.96 mg kg-1). In leaves,
      As(III) significantly increased (P < 0.05) as the treatment duration increased.
      The proportions of As(V) (27.99-40.03%) were lower than those of As(III) and
      arsenobetaine (AsB) was detected (0.52-1.87 mg kg-1) after 7 d. The results of
      arsenic speciation demonstrated that the transformation of arsenic species in V.
      natans included As(V) reduction and As(III) methylation to AsB. There were a
      decrease in chlorophyll content, and an increase in MDA level and antioxidant
      enzymes (SOD, CAT, and POD) activities. The MDA level was much higher in leaves
      than roots, whereas the activities of SOD, CAT, and POD were the opposite,
      suggesting their possible role in arsenic resistance and detoxification. Our
      results indicate the potential of V. natans in phytoremediation of arsenic
      contaminated water.

PMID- 30199794
TI  - Groundwater fluoride removal using modified mesoporous dung carbon and the impact
      of hydrogen-carbonate in borehole samples.
AB  - There have been many research reports pertained to the interference of co - ions
      including hydrogen carbonate against the removal of fluoride from water. In this
      context, the present research explores the fluoride removal efficiency of
      ammonium carbonate modified dung derived carbon (DDC500) in the absence and
      presence of hydrogen carbonate using synthetically made fluoride solutions and
      groundwater samples. The adsorbent DDC500 was found to achieve the highest
      removal of 80% of fluoride at pH 6.95 than the washed carbon (DDC500W) and dung
      ash (DA) of 48% and 23% respectively. In DDC500, the carbon base in concert with
      inorganic residues actively functioned in the fluoride removal process and chosen
      for synthetic fluoride solutions (2-5 mg L-1) and 16 groundwater samples (2.1-3.6
      mg L-1) from 10 locations of Usilampatti Taluk in Madurai District, South India.
      After the removal of hydrogen carbonate in groundwater, the percentage of samples
      was increased in accordance with the safe limits of World Health Organization
      (WHO) and Bureau of Indian Standard (BIS). Langmuir isotherm model (R2 = 0.9379)
      was in concordance with the adsorption of fluoride from groundwater free from
      hydrogen carbonate. The dynamics of other groundwater quality parameters at
      conditions and the independency between F-/HCO3- ratio and DE were illustrated by
      scatter plots. Characterization studies for the dried dung (CD110), derived
      carbons (DDC500 and DDC500W) and ashes (CD110A, DDC500A and DDC500WA) using FE
      SEM, XRD, FTIR, Raman and TGA - EGA were done to understand the nature and
      behavior of materials.

PMID- 30199795
TI  - Ecological stoichiometry-based study of the influence of soil saline-alkali
      stress on nutrient homeostasis in L. chinensis.
AB  - Soil salinization is a major cause of land degradation and hinders the effective
      utilization of agricultural land resources. Leymus chinensis (L. chinensis), as a
      dominant species with wide ecological amplitude, plays an important role in
      improving saline-alkali grasslands and indicating the degree of salinization. In
      this study, a sand culture experiment (nitrogen and phosphorus addition
      accompanied by saline-alkali stress) was designed to investigate the impact of
      different saline-alkali environments on the ecological stoichiometric homeostasis
      of L. chinensis with the aim of elucidating the saline-alkali resistance
      mechanisms. The results showed that the homeostasis indexes of N, P and N:P in
      the aboveground part of L. chinensis were generally higher than those in the
      belowground part under different saline-alkali conditions. Furthermore, the
      homeostasis index of N (HN) was greater than that of P (HP) in the aboveground
      part, whereas HN was less than HP in the belowground part. This indicates that
      the growth aboveground of L. chinensis was mainly dependent on N, whereas the
      growth belowground was mainly affected by P. The homeostasis index of the
      aboveground organs was 4.45-12.93 under pH 7-9.8. In contrast, HN and HN:P(+N) in
      the belowground organs did not conform to a homeostasis model when pH > 9.1.
      Consequently, when L. chinensis is subjected to high saline-alkali stress, the
      homeostasis reaction of the roots is more sensitive than that of the aboveground
      organs.

PMID- 30199796
TI  - Transcriptome analysis reveals complex response of the medicinal/ornamental
      halophyte Iris halophila Pall. to high environmental salinity.
AB  - The remediation and subsequent use of saline-alkaline land are of great
      significance to ecological environment construction and sustainable agricultural
      development. Iris halophila Pall. is a salt-tolerant medicinal and ornamental
      plant, which has good application prospects in the ecological construction of
      saline-alkaline land; therefore, study of the molecular mechanisms of salt
      tolerance in I. halophila has important theoretical and practical value. To
      evaluate the molecular mechanism of the response of I. halophila to salt
      toxicity, I. halophila seedlings were treated with salt (300 mM NaCl) and
      subjected to deep RNA sequencing. The clean reads were obtained and assembled
      into 297,188 unigenes. Among them, 1120 and 100 salt-responsive genes were
      identified in I. halophila shoots and roots, respectively. Among them, the key
      flavonoid and lignin biosynthetic genes, hormone signaling genes,
      sodium/potassium ion transporter genes, and transcription factors were analyzed
      and summarized. Quantitative reverse-transcription PCR analysis strengthened the
      reliability of the RNA sequencing results. This work provides an overview of the
      transcriptomic responses to salt toxicity in I. halophila and identifies the
      responsive genes that may contribute to its reduced salt toxicity. These results
      lay an important foundation for further study of the molecular mechanisms of salt
      tolerance in I. halophila and related species.

PMID- 30199797
TI  - Hazardous effects of chemical pesticides on human health-Cancer and other
      associated disorders.
AB  - Poisoning from pesticides is a global public health problem and accounts for
      nearly 300,000 deaths worldwide every year. Exposure to pesticides is inevitable;
      there are different modes through which humans get exposed to pesticides. The
      mode of exposure is an important factor as it also signifies the concentration of
      pesticides exposure. Pesticides are used extensively in agricultural and domestic
      settings. These chemicals are believed to cause many disorders in humans and
      wildlife. Research from past few decades has tried to answer the associated
      mechanism of action of pesticides in conjunction with their harmful effects. This
      perspective considers the past and present research in the field of pesticides
      and associated disorders. We have reviewed the most common diseases including
      cancer which are associated with pesticides. Pesticides have shown to be involved
      in the pathogenesis of Parkinson's and Alzheimer's diseases as well as various
      disorders of the respiratory and reproductive tracts. Oxidative stress caused by
      pesticides is an important mechanism through which many of the pesticides exert
      their harmful effects. Oxidative stress is known to cause DNA damage which in
      turn may cause malignancies and other disorders. Many pesticides have shown to
      modulate the gene expression at the level of non-coding RNAs, histone
      deacetylases, DNA methylation patterns suggesting their role in epigenetics.

PMID- 30199798
TI  - An approach to a muscle force model with force-pulse amplitude relationship of
      human quadriceps muscles.
AB  - BACKGROUND: Recent advanced applications of the functional electrical stimulation
      (FES) mostly used closed-loop control strategies based on mathematical models to
      improve the performance of the FES systems. In most of them, the pulse amplitude
      was used as an input control. However, in controlling the muscle force, the most
      popular force model developed by Ding et al. does not take into account the pulse
      amplitude effect. The purpose of this study was to include the pulse amplitude in
      the existing Ding et al. model based on the recruitment curve function. METHODS:
      Quadriceps femoris muscles of eight healthy subjects were tested. Forces
      responses to stimulation trains with different pulse amplitudes (30-100 mA) and
      frequencies (20-80 Hz) were recorded and analyzed. Then, specific model parameter
      values were identified by fitting the measured forces for one train (50 Hz, 100
      mA). The obtained model parameters were then used to identify the recruitment
      curve parameter values by fitting the force responses for different pulse
      amplitudes at the same frequency train. Finally, the extended model was used to
      predict force responses for a range of stimulation pulse amplitudes and
      frequencies. RESULTS: The experimental results indicated that our adapted model
      accurately predicts the force-pulse amplitude relationship with an excellent
      agreement between measured and predicted forces (R2=0.998, RMSE = 6.6 N).
      CONCLUSIONS: This model could be used to predict the pulse amplitude effect and
      to design control strategies for controlling the muscle force in order to obtain
      precise movements during FES sessions using intensity modulation.

PMID- 30199799
TI  - Diversity of potential antibiotic-resistant bacterial pathogens and the effect of
      suspended particles on the spread of antibiotic resistance in urban recreational
      water.
AB  - Evidence of the increasing incidence of antibiotic resistance in watersheds has
      attracted worldwide attention. Limited in formation is available on the
      occurrences of health-related antibiotic-resistant bacterial pathogens (ARBPs) in
      recreational waters. The effects of certain environmental factors (e.g.,
      suspended particles) on the spread of resistance also has not been characterized
      to date. In this study, a combination of culture and molecular methods was
      employed to comprehensively investigate the patterns of microbial resistance to
      representative antibiotics in samples from three recreational lakes in Beijing.
      The antibiotic resistance index (ARI) based on the gradient concentration assay
      revealed that samples showed high resistance to penicillin-G, moderate resistance
      to ampicillin, vancomycin and erythromycin and low resistance to ceftriaxone,
      gentamycin, tetracycline and chloramphenicol. Antibiotic-resistant bacteria (ARB)
      were cultured and collected, and the diversity of potential ARBP species was
      further explored using next-generation sequencing (NGS). The results showed that
      most of the identified ARBPs were environmental opportunistic pathogens with
      emerging clinical concerns, e.g., the multidrug-resistant Acinetobacter junii.
      Furthermore, particle-attached (PA) fractions presented higher ARI values than
      free-floating (FL) fractions did, indicating that the PA fractions were more
      resistant to selected antibiotics. And the NGS results revealed that the PA
      fractions showed higher similarity in the screened ARB community compositions in
      comparison with the FL fractions, primarily due to a protective effect provided
      by the particles. Accordingly, ARBPs could persist for a longer time in
      protective particle matrices. However, quantification of antibiotic-resistant
      genes (ARGs) by qPCR showed no significant abundance differences between the two
      fractions. Overall, these findings suggest a potential health risk from the
      prevalence of ARBPs in recreational waters and provides a better understanding of
      the contribution of particles in the spread of antibiotic resistance in aquatic
      systems, with implications for the control of excessive suspended particles by
      water management.

PMID- 30199800
TI  - The more important role of archaea than bacteria in nitrification of wastewater
      treatment plants in cold season despite their numerical relationships.
AB  - Nitrification failure of wastewater treatment plants (WWTPs) in cold season calls
      into investigations of the functional ammonia-oxidizing microorganisms (AOMs). In
      this study, we report the abundance of ammonia-oxidizing archaea (AOA), bacteria
      (AOB) and complete ammonia-oxidizing (comammox) Nitrospira in 23 municipal WWTPs
      in cold season, and explore the correlations between AOMs abundance and their
      relative contribution to nitrification. The copy numbers of AOA and AOB amoA gene
      ranged from 2.42 * 107 to 2.47 * 109 and 5.54 * 106 to 3.31 * 109 copies/g
      sludge, respectively. The abundance of amoA gene of Candidatus Nitrospira
      inopinata, an important strain of comammox Nitrospira, was stable with averaged
      abundance of 8.47 * 106 copies/g sludge. DNA-based stable isotope probing (DNA
      SIP) assays were conducted with three typical WWTPs in which the abundance of AOA
      was lower than, similar to and higher than that of AOB, respectively. The results
      showed that considerable 13C-assimilation by AOA was detected during active
      nitrification in all WWTPs, whereas just a much lesser extent of 13C
      incorporation by AOB and comammox Nitrospira was found in one WWTP. High
      throughput sequencing with 13C-labeled DNA also showed the higher reads abundance
      of AOA than AOB and comammox Nitrospira. Nitrososphaera viennensis was the
      dominant active AOA, while Nitrosomonas oligotropha and Nitrosomonas europaea
      were identified as active AOB. The results obtained suggest that AOA, rather than
      AOB and comammox Nitrospira, dominate ammonia oxidation in WWTPs in cold season
      despite the numerical relationships of AOMs.

PMID- 30199801
TI  - Field performance of two biofiltration systems treating micropollutants from road
      runoff.
AB  - The treatment efficiency of a vegetative filter strip and a biofiltration swale
      treating heavily loaded road runoff are evaluated. Concentrations measured in
      water drained from the two systems are compared to those in untreated road runoff
      collected from a reference catchment for a wide range of contaminants including
      organic carbon, nutrients (N and P), trace metals, and organic micropollutants
      (polycyclic aromatic hydrocarbons (PAH), total petroleum hydrocarbons (TPH),
      alkylphenols, bisphenol-A, phthalates), in both total and dissolved phases.
      Predominantly particulate pollutants, including Pb, Zn and PAH, were very
      efficiently removed (around 90%) for most events. However, poor particulate
      removal was observed during a winter period. Relatively few pollutants were
      significantly removed in the dissolved phase and observed concentration
      reductions tended to be lower than those of suspended solids and associated
      pollutants; as such, lower removals were observed for total concentrations of
      moderately particulate micropollutants, including bisphenol-A, alkylphenols and
      phthalates. In addition, some pollutants appear to be emitted from various
      biofilter components (filter media, drainage and lining materials), as low or
      negative concentration removals were observed during the first months of
      operation of the biofiltration swale.

PMID- 30199802
TI  - A facile and green pretreatment method for nonionic total organic halogen (NTOX)
      analysis in water - Step II. Using photolysis to convert NTOX completely into
      halides.
AB  - Adsorbable organic halogen (AOX) is a parameter conventionally used to indicate
      the sum of organic halogenated disinfection byproducts (DBPs), which are formed
      from the reactions of disinfectants with dissolved organic matter, bromide and
      iodide in water. To overcome the issues of the AOX analytical method, we proposed
      a new facile and green pretreatment method to enable the analysis of nonionic
      total organic halogen (NTOX) via the following three steps: 1) separation of NTOX
      and halides with electrodialysis, 2) conversion of NTOX with ultraviolet (UV)
      photolysis, and 3) analysis of halides with ion chromatography. To verify this
      proposal, we mainly evaluated the efficiency of vacuum ultraviolet (VUV) coupled
      with UV photolysis (VUV-UV) in converting NTOX into halides. Results showed that
      by applying VUV irradiation for 60 min and UV irradiation at pH 10-11 for another
      30 min, over 85.5% of each halide from 20 representative small molecular weight
      DBPs (each at 100 MUg-X/L level) was recovered. The purpose of UV photolysis
      under alkaline conditions was to reduce oxyhalides (such as bromate and iodate)
      formed in the VUV process back to halides. With the aid of electrospray
      ionization-triple quadrupole mass spectrometry, we captured the whole pictures of
      high molecular weight polar DBPs in a chlorinated drinking water before and after
      VUV-UV, through which averagely 96.4% of dehalogenation with the VUV-UV treatment
      was observed. An illustrative comparison of the conventional AOX method and the
      proposed NTOX method indicates that although the detected NTOX was lower (by 2.3
      30.6%) than AOX, the results of the two methods were highly correlated (R2 >
      0.97). All these hence verified the photolysis as a mature yet novel tool for
      sample pretreatment in environmental analytical chemistry.

PMID- 30199803
TI  - Determination of mechanical properties of biofilms by modelling the deformation
      measured using optical coherence tomography.
AB  - The advantage of using non-invasive imaging such as optical coherence tomography
      (OCT) to asses material properties from deformed biofilm geometries can be
      compromised by the assumptions made on fluid forces acting on the biofilm. This
      study developed a method for the determination of elastic properties of biofilms
      by modelling the biofilm deformation recorded by OCT imaging with poroelastic
      fluid-structure interaction computations. Two-dimensional biofilm geometries were
      extracted from OCT scans of non-deformed and deformed structures as a result of
      hydrodynamic loading. The biofilm geometries were implemented in a model coupling
      fluid dynamics with elastic solid mechanics and Darcy flow in the biofilm. The
      simulation results were compared with real deformed geometries and a fitting
      procedure allowed estimation of the Young's modulus in given flow conditions. The
      present method considerably improves the estimation of elastic moduli of biofilms
      grown in mini-fluidic rectangular channels. This superior prediction is based on
      the relaxation of several simplifying assumptions made in past studies: shear
      stress is not anymore taken constant over the biofilm surface, total stress
      including also pressure is accounted for, any biofilm shape can be used in the
      determinations, and non-linear behavior of mechanical properties can be
      estimated. Biofilm elastic moduli between 70 and 700 Pa were obtained and biofilm
      hardening at large applied stress due to increasing flow velocity was quantified.
      The work performed here opens the way for in-situ determination of other
      mechanical properties (e.g., viscoelastic properties, relaxation times, plastic
      yields) and provides data for modelling biofilm deformation and detachment with
      eventual applications in biofilm control and removal strategies.

PMID- 30199804
TI  - Development of anti-biofouling feed spacers to improve performance of reverse
      osmosis modules.
AB  - This study investigates the biofouling resistance of modified reverse osmosis
      (RO) feed spacers. Control spacers (made of polypropylene) were functionalized
      with a biocidal coating (silver), hydrophilic (SiO2 nanoparticles) or
      superhydrophobic (TMPSi-TiO2 nanoparticles) anti-adhesive coatings, or a hybrid
      hydrophilic-biocidal coating (graphene oxide). Performance was measured by
      adhesion assays, viability tests, and permeate flow decline in a bench scale RO
      system. The control spacers proved to be one of the better performing materials
      based on bacterial deposition and dynamic RO fouling experiments. The good anti
      adhesive properties of the control can be explained by its near ideal surface
      free energy (SFE). The only surface modification that significantly reduced
      biofouling compared to the control was the biocidal silver coating, which
      outperformed the other spacers by all measured indicators. Therefore, future
      efforts to improve spacer materials for biofouling control should focus on
      engineering biocidal coatings, rather than anti-adhesive ones.

PMID- 30199805
TI  - Removal of phosphonates from synthetic and industrial wastewater with reusable
      magnetic adsorbent particles.
AB  - This work proposes a technology for phosphonate removal from wastewater using
      magnetically separable microparticles modified with a tailored ZnFeZr
      oxyhydroxide adsorbent material which proved to be highly efficient, reaching a
      maximum loading of ~20 mg nitrilotrimethylphosphonic acid-P/g (215 MUmol NTMP/g)
      at room temperature, pH 6 and 30 min contact time. The adsorption process at pH <
      7 was fast, following the pseudo-second-order kinetics model. Furthermore, NTMP
      adsorption onto ZnFeZr-oxyhydroxide proved to be endothermic. At pH > pHpzc ~7
      (point of zero charge of the material) a drop in adsorption efficiency was
      observed for phosphate and for five different investigated phosphonates.
      Adsorption of NTMP could not be detected at pH > 8, however, the presence of more
      than 0.5 mM CaII improved significantly the adsorption efficiency. Successful
      reusability of the engineered particles was demonstrated throughout 30 loading
      cycles by changing the operational conditions (dose, pH) to optimize the
      performance. At optimal conditions, complete phosphonate removal was observed
      even after 30 cycles of particles' reuse in a synthetic NTMP-solution and DTPMP
      rich membrane concentrate. In each cycle, phosphorus was desorbed and
      concentrated in a 2 M NaOH. Industrial phosphonate-containing wastewaters rich in
      calcium, e.g. membrane concentrates, proved to be especially suitable for
      treatment with the particles.

PMID- 30199806
TI  - Modelling the potential for multi-location in-sewer heat recovery at a city scale
      under different seasonal scenarios.
AB  - A computational network heat transfer model was utilised to model the potential
      of heat energy recovery at multiple locations from a city scale combined sewer
      network. The uniqueness of this network model lies in its whole system validation
      and implementation for seasonal scenarios in a large sewer network. The network
      model was developed, on the basis of a previous single pipe heat transfer model,
      to make it suitable for application in large sewer networks and its performance
      was validated in this study by predicting the wastewater temperature variation
      across the network. Since heat energy recovery in sewers may impact negatively on
      wastewater treatment processes, the viability of large scale heat recovery was
      assessed by examining the distribution of the wastewater temperatures throughout
      a 3000 pipe network, serving a population equivalent of 79500, and at the
      wastewater treatment plant inlet. Three scenarios; winter, spring and summer were
      modelled to reflect seasonal variations. The model was run on an hourly basis
      during dry weather. The modelling results indicated that potential heat energy
      recovery of around 116, 160 & 207 MWh/day may be obtained in January, March and
      May respectively, without causing wastewater temperature either in the network or
      at the inlet of the wastewater treatment plant to reach a level that was
      unacceptable to the water utility.

PMID- 30199807
TI  - A facile and green pretreatment method for nonionic total organic halogen (NTOX)
      analysis in water - Step I. Using electrodialysis to separate NTOX and halides.
AB  - Adsorbable organic halogen (AOX) is a bulk organic parameter conventionally used
      to indicate all adsorbable halogenated organic disinfection byproducts formed in
      disinfected water. Analytically, AOX is determined by three sequential steps: 1)
      concentration and separation of AOX from halides with activated carbon, 2)
      conversion of AOX into halides with pyrolysis, and 3) quantification of halides
      via microcoulometry or ion chromatography (IC). Because the approach is
      relatively costly and cannot effectively recover non-adsorbable compounds, we
      herein proposed a facile and green pretreatment tool to measure the nonionic
      portion of total organic halogen (NTOX) with a new three-step approach: 1)
      separation of NTOX and halides with electrodialysis (ED), 2) conversion of NTOX
      into halides with ultraviolet, and 3) analysis of halides with IC. To verify this
      proposal, this study presented the efficiency of ED in separating halides and
      NTOX under a variety of operational and environmental conditions. The results
      showed that ED removed >=98.5% of fluoride, chloride, bromide, and iodide from
      all tested waters (up to 1000 mg-X/L) within 1.5 h. Meanwhile, ED recovered an
      average of 87.9% of fourteen small molecular weight model compounds with each at
      100 MUg/L. By using electrospray ionization-triple quadrupole mass spectrometry,
      the whole pictures of high molecular weight compounds in a chlorinated drinking
      water before and after ED pretreatment were compared, which revealed 79.7% and
      83.6% recoveries of overall polar chlorinated and brominated compounds,
      respectively. In addition, the quantity and property of the dissolved organic
      matter were largely maintained by ED, and the retained organics may be used for
      later characterization. The study hence presents a novel use of ED as a
      pretreatment tool to enable subsequent NTOX measurement.

PMID- 30199808
TI  - A chemical derivatization based UHPLC-LTQ-Orbitrap mass spectrometry method for
      accurate quantification of short-chain fatty acids in bronchoalveolar lavage
      fluid of asthma mice.
AB  - Recent studies have demonstrated the important role of short-chain fatty acids
      (SCFAs) in the maintenance of homeostasis of respiratory immunity. However, there
      is still no report focus on the determination of SCFAs level in bronchoalveolar
      lavage fluid (BALF), the most common sample used for screening biomarkers of the
      pulmonary diseases. Herein, an ultra-high-performance liquid chromatography with
      LTQ-Orbitrap mass spectrometer (UHPLC-LTQ-Orbitrap) oriented 3
      nitrophenylhydrazine (3-NPH)-based derivatization method was developed for the
      quantification of SCFAs in BALF. To achieve accurate quantitation, d4-acetate was
      used as internal standard to compensate for the matrix effects. Method validation
      showed a good linearity (R2 > 0.9992) with wide concentration range, and the
      intra-day and inter-day precision for determination of eight SCFAs in BALF
      samples was <= 14.79%. The quantitation accuracy, assessed by relative
      recoveries, ranged from 90% to 110% for target SCFAs at three concentration
      levels. Matrix effects ranged from 85% to 115%, and the lower limits of
      quantification of these targeted SCFAs were varied from 3 to 24 nmol/L. The SCFAs
      targeted method was then applied to determine the changed levels in BALF samples
      from OVA-induced asthma mice and normal mice. In addition, the universality of
      our developed method was also demonstrated by determining the SCFAs
      concentrations in feces, serum and lung tissue samples from asthma and normal
      mice. These results indicate that 3-NPH derivatization based UHPLC-LTQ-Orbitrap
      provides accurate view of global SCFAs alternation in different samples, giving a
      support to deduce the origin of SCFAs in lung. The present study is of great
      importance for understanding the role of SCFAs in modulation of host metabolism
      and immunity.

PMID- 30199809
TI  - Investigation of the inhibition effect of arachidonic acid on the core structure
      of the HIV-1 gp41.
AB  - The gp41 transmembrane domain of the envelope glycoprotein of the human
      immunodeficiency virus (HIV) modulates the conformation of the viral envelope
      spike. During the HIV fusion process, C-terminal heptad repeat (CHR, C34) wrap
      antiparallel to the N-terminal heptad repeat (NHR, N36) helices to form a stable
      six-helix bundle (6-HB) core structure, which brings the viral and cell membranes
      into close proximity for fusion. Therefore, inhibiting the formation of 6-HB is
      considered to be a key activity of an effective HIV-1 fusion inhibitor. The level
      of arachidonic acid (AA) is increased in HIV infected patients. Our study
      provides a new insight into the functional role of AA during the formation of HIV
      1 gp41 6-HB. Native polyacrylamide gel electrophoresis (N-PAGE), enzyme-linked
      immunosorbent serologic assay (ELISA) and circular dichroism (CD) spectroscopy
      were used to investigate the inhibition of AA for the formation of 6-HB.
      Molecular docking technique was adopted to explore the underlying mechanism. HIV
      1 JR-FL (R5 strain) Envelope was adopted to determine the inhibition effect of
      AA. AA is shown to interfere with the formation of alpha-helical complexes of N36
      and C34 by N-PAGE, ELISA and CD spectroscopy. The isotherm titration
      microcalorimetry (ITC) results indicate there is a single class of binding site
      on N36. DeltaH and DeltaS are -12.43 kJ mol-1 and 70.07 J mol-1 K-1,
      respectively, indicating hydrophobic interaction and electrostatic forces are the
      main acting forces. The molecular docking results manifest that AA interacts with
      the hydrophobic residues (Trp-571, Leu-568, Val-570 and Leu-576) and ionic
      interactions occur between Arg-579 and the -COOH of AA. The inhibitory activity
      of AA on HIV-1 JR-FL is quantified by 50% effective concentration (EC50) and 90%
      effective concentration (EC90), which are 31.42 +/- 1.08 and 133.47 +/- 18.10 MUg
      mL-1, respectively. All the results indicate that AA is able to inhibit the
      formation of 6-HB but cannot disrupt the preformed 6-HB. Therefore, AA is a
      potential inhibitor for the viral fusion/entry.

PMID- 30199810
TI  - Influence of the geographic proximity of city features on the spatial variation
      of urban carbon sinks: A case study on the Pearl River Delta.
AB  - Locations of city features, e.g., city centers, roads, railways, and rivers, may
      impact urban carbon sinks. Therefore, the effects of city features on spatial
      variations of urban carbon sinks were investigated using geographic proximity
      data. The main results were as follows. (1) Carbon sink function varied in a
      complex manner with distance from the city center and with city size. The carbon
      sink per unit area increased with distance from the prefecture-level city center
      (0-30 km), with the dominant influence occurring within a 9 km radius. The lowest
      carbon sink per unit area was observed at a distance of 12 km from the city
      center of the provincial capital city (Guangzhou) and special economic zone
      (Shenzhen), which may be suburban industrial zones. (2) Carbon sinks decreased
      with increases in road grades as a result of the different functions and traffic
      flow, and carbon sinks were lowest near city express ways. For highways, carbon
      sinks were lower near highway entrances and exits. Carbon sinks around ordinary
      railways were higher than those around subways and light rail, but carbon sink
      characteristics grew more complex with increasing distances from subways and
      light rail. (3) Rivers were closely related to the urban layout. Grade I (i.e.,
      larger) rivers were associated with lower carbon sinks, and carbon sink
      characteristics became increasingly complex around larger rivers. Within a 0-1000
      m distance of all rivers, the carbon sink per unit area increased rapidly, but
      carbon sink characteristics differed slightly for grade I rivers. This study
      implies that it is important to take urbanization spatial position effects into
      account while assessing regional carbon sinks during urbanization and
      development.

PMID- 30199811
TI  - Oral bioaccessibility of silver nanoparticles and ions in natural soils:
      Importance of soil properties.
AB  - The abundance of silver nanoparticles (AgNPs) in consumer products has led to
      their environmental release and therefore to concern about their impact on human
      health. The ingestion of AgNP-contaminated soil from urban sites is an important
      exposure pathway, especially for children. Given the limited information on oral
      bioaccessibility of soil Ag, we used a physiologically based extraction test
      (PBET) to evaluate the bioaccessibility of AgNPs and AgNO3 from soil digestion.
      The AgNPs underwent several biochemical transformations, including their
      simultaneous dissolution and agglomeration in gastric fluid followed by the
      disintegration in the intestinal fluid of the agglomerates into NPs containing
      silver and chlorine. Therefore, Ag-containing soil exposed the intestine to
      nanoparticulate Ag in forms that were structurally different from the original
      forms. The bioaccessibility of AgNPs (0.5 +/- 0.05%-10.9 +/- 0.7%) was
      significantly lower than that of AgNO3 (4.7 +/- 0.6%-14.4 +/- 0.1%), as a result
      of the lower adsorption of nanoparticles to soil residues during the digestive
      process. For the soils tested, the bioaccessibility of AgNPs increased with
      decreasing clay contents and lower pH. By identifying the soil properties that
      control AgNP bioaccessibility, a more efficient and accurate screening can be
      performed of soil types that pose the greatest health risk associated with AgNP
      exposure.

PMID- 30199812
TI  - Chemometrics analysis of petroleum hydrocarbons sources in the street dust,
      runoff and sediment of urban rivers in Anzali port - South of Caspian Sea.
AB  - Major sources of petroleum hydrocarbons in the south of Caspian Sea (Anzali city)
      have been investigated through an approach which combines Gas Chromatography-Mass
      Spectrometry with Principal Component Analysis (PCA) and Multivariate Curve
      Resolution-Alternating Least Squares chemometric methods. Terpane, catagenetic
      hopane and sterane hydrocarbons were analyzed in the street dust, filtered
      sediments of runoff, soluble runoff water and river sediment samples as well as
      in automobiles exhaust, tires, asphalt, engine oil, gasoline and diesel samples,
      as possible sources of these hydrocarbons. PCA and MCR-ALS results showed that a
      large part of the analyzed hydrocarbons in street dust, runoffs and in some of
      the river sediment samples can be explained by the proposed known sources, while
      the observed variation of hydrocarbon concentrations in many of the river
      sediment samples was not much affected by the proposed known sources, and they
      were most probably receiving other pollution sources not included in our study.
      This study also has shown that results obtained from hydrocarbon marker molecular
      ratios, to identify petroleum pollution sources in the environments, are in
      agreement with those obtained from pollution sources resolved by MCR-ALS
      simultaneous analysis of all samples and variables.

PMID- 30199813
TI  - Differences in reproductive toxicity of TBBPA and TCBPA exposure in male Rana
      nigromaculata.
AB  - Tetrabromobisphenol A (TBBPA) and tetrachlorobisphenol A (TCBPA) are persistent
      toxic environmental pollutants that cause severe reproductive toxicity in
      animals. The goal of this study was to compare the reproductive toxic effects of
      TBBPA and TCBPA on male Rana nigromaculata and to expound on the mechanisms
      leading to these effects. Healthy adult frogs were exposed to 0, 0.001, 0.01,
      0.1, and 1 mg/L of TBBPA and TCBPA for 14 days. Sperm numbers were counted by
      erythrometry. Sperm mobility and deformities were observed under a light
      microscope (400 * ). We used commercial ELISA kits to determine the serum content
      of testosterone (T), estradiol (E2), luteinizing hormone (LH) and follicle
      stimulating hormone (FSH). Expression of androgen receptor (AR) mRNA was detected
      using real-time qPCR. Sperm numbers and sperm mobility were significantly
      decreased and sperm deformity was significantly increased in a concentration
      dependent manner following exposure to TBBPA and TCBPA. Sperm deformity was
      significantly greater in the 1 mg/L TCBPA (0.549) treatment group than in the 1
      mg/L TBBPA (0.397) treatment group. Serum T content was significantly greater in
      the 0.01, 0.1 and 1 mg/L TBBPA and TCBPA experimental groups compared with
      controls, while E2 content was significantly greater in only the 1 mg/L TBBPA and
      TCBPA experimental groups. Expression levels of LH and FSH significantly
      decreased in the 1 mg/L TBBPA and TCBPA treatment groups. AR mRNA expression
      decreased markedly in all the treated groups. Our results indicated that TBBPA
      and TCBPA induced reproductive toxicity in a dose-dependent manner, with TCBPA
      having greater toxicity than TBBPA. Furthermore, changes in T, E2, LH, and FSH
      levels induced by TBBPA and TCBPA exposure, which led to endocrine disorders,
      also caused disturbance of spermatogenesis through abnormal gene expressions of
      AR in the testes.

PMID- 30199814
TI  - Assessment of NICE and USPSTF guidelines for identifying women at high risk of
      pre-eclampsia for tailoring aspirin prophylaxis in pregnancy: An individual
      participant data meta-analysis.
AB  - OBJECTIVE: To assess the accuracy of the National Institute of Health and Care
      Excellence (NICE) and United States Preventive Services Task Force (USPSTF)
      guidelines for predicting pre-eclampsia in pregnancy to guide aspirin
      prophylaxis. STUDY DESIGN: We conducted an individual participant data meta
      analysis using the Perinatal Antiplatelet Review of International Studies (PARIS)
      dataset. This dataset includes randomised controlled trials (RCTs) of
      antiplatelet therapy for primary prevention of pre-eclampsia conducted in
      international antenatal care settings. RCTs were eligible if they enrolled
      pregnant women up to 28 weeks'gestation, reported risk factors, and assessed pre
      eclampsia. Women assigned to the control arm (no antiplatelet agent) were
      included. Both guidelines recommend aspirin if >=1 high-risk factors or >=2
      moderate-risk factors. Two moderate-risk factors (body mass index and pregnancy
      interval) were unavailable. Pre-eclampsia was the primary outcome. The secondary
      outcomes were pre-eclampsia defined by gestational age at delivery (<37 weeks
      versus >=37 weeks; <34 weeks versus >=34 weeks). We assessed the performance of
      the NICE and USPSTF approaches for parous and nulliparous women by estimating
      sensitivity, specificity, positive predictive value (PPV) and negative predictive
      value (NPV) for predicting pre-eclampsia, the number-needed-to-screen (NNS) and
      the number-needed-to-treat (NNT) to prevent one pre-eclampsia event. RESULTS:
      Three RCTs were eligible (4524 women, 221 pre-eclampsia cases). Using the NICE
      guidelines, 9.4% of 1020 parous women were classified as screen-positive with a
      sensitivity of 26.4% (95% confidence interval 16.4-39.6%), specificity 91.5%
      (89.6-93.1%), PPV 14.6% (8.9-23.0%) and NPV 95.8% (94.3-96.9%). The NNS was 729
      and NNT 69. For 3504 nulliparous women, 3% were classified as screen-positive
      with a sensitivity of 8.9% (5.5-14.4%), specificity 97.2% (96.6-97.8%), PPV 14.2%
      (8.7-21.9%), NPV 95.5% (94.8-96.1%). The NNS was 2336 and NNT 71. The USPSTF
      approach demonstrated similar performance. CONCLUSION: The NICE and USPSTF
      guidelines offer a simple and specific approach for recommending aspirin
      prophylaxis for women at high-risk of pre-eclampsia where more advanced screening
      methods are not available. However, the low detection rate limits its value in
      clinical practice, in particular for nulliparous women, and raises the need for
      development of an improved simple risk prediction tool.

PMID- 30199815
TI  - An innovative dual-phase protocol for pulsed ablative vaginal Erbium:YAG laser
      treatment of urogynecological symptoms.
AB  - OBJECTIVES: To evaluate a dual-phase protocol for vaginal ablative Erbium:YAG
      laser treatment in pelvic floor medicine. STUDY DESIGN: Data from consecutive
      patients undergoing vaginal Erbium:YAG laser for first-degree pelvic floor
      complaints at a certified university urogynecological unit were analyzed.
      Fractional ablative and thermal treatment with adjustable pulse duration,
      fluence, and pulse interval was performed in single ten-minute treatment course.
      Followed up interval was 6 weeks including interviews on expectations, goal
      setting, goal achievement, and satisfaction (EGGS), vaginal pH, and determination
      of the Gloria-Bachmann-Index (VHI). Post-procedural complications were classified
      according to definition and classification of the Clavien-Dindo system. RESULTS:
      Of 84 patients treated, 71 (21% pre-, 79% post-menopausal) were evaluated. 27%
      had single urogynecological symptoms, 35% had three or more combined symptoms.
      Minor post-procedural complications occurred in three patients (CD I, n = 1; CD
      II, n = 3). The ranges of fluence, determined according to the atrophy state, in
      the first and second phases were 15-35 and 3-12 J/cm2, respectively. In patients
      with genitourinary syndrome of menopause, pre- and post-treatment VHI and pH
      differed significantly [15.3 +/- 4.5 vs. 19.9 +/- 2.8 (p < 0.001, Student's t
      test) and 5.2 +/- 0.6 vs. 4.8 +/- 0.4 (p =  0.024, respectively]. Overall, 82% (n
      = 58; mean age, 58 +/- 12 years) of patients were satisfied with the treatment,
      84% (47/56) post-menopausal patients were satisfied. CONCLUSIONS: Vaginal
      ablative Erbium:YAG laser dual-phase protocol for early urogynecological symptoms
      was successful and safe, with high patient satisfaction and few, minor
      complications. Prospective studies are needed to confirm our first data.

PMID- 30199816
TI  - Shedding light on the fertility preservation debate in women with endometriosis:
      a swot analysis.
AB  - Endometriosis, a hormone-dependant condition affecting around 10% of women in
      their reproductive years, has frequent consequences on fertility. Indeed, a
      proportion of women will require assisted reproductive techniques or surgery in
      order to achieve pregnancy. Recent refining of stimulation protocols and
      vitrification techniques has created new possibilities in the field of fertility
      preservation. As a consequence, oocyte vitrification is now discussed not only in
      oncologic situations, but also in other conditions at risk of altered ovarian
      reserve and poor fertility outcome. In endometriosis, various mechanisms can
      impair ovarian function and diminish ovarian, particularly bilateral or repeated
      cystectomy. Fertility preservation could represent an option for women with
      endometriosis but still remains controversial. In order to shed some light on
      this complex subject and to outline different issues at stake we conducted a SWOT
      analysis highlighting strengths, weaknesses, opportunities and threats of oocyte
      vitrification in women with endometriosis.

PMID- 30199817
TI  - Chromatographic separation of R/S-enantiomers of amphetamine and methamphetamine:
      Pathways of methamphetamine synthesis and detection in blood samples by
      qualitative enantioselective LC-MS/MS analysis.
AB  - Methamphetamine can be synthesized either enantiopure or in its racemic form. We
      separated (R)- and (S)-enantiomers of methamphetamine and amphetamine by a fast
      LC-MS/MS-method using a Lux(r) 3MUm AMP 150*3.0mm analytical column after simple
      protein precipitation with methanol. Sufficient resolution could be achieved.
      Method validation for qualitative detection showed limits of quantification
      <5ng/mL while only little (maximum 14.5%) ion suppression could be shown.
      Stability in the processed sample could be achieved using isotopically labelled
      internal standards. Plasma samples of police cases from the german regions of
      Franconia and Northrhine revealed that in the majority of 106 tested samples
      (>99%) only (S)-methamphetamine was detected which leads to the conclusion that,
      in Germany, predominantly enantiopure (S)-methamphetamine is consumed which is
      synthesized via (1R,2S)-ephedrine or (1S,2S)-pseudoephedrine. However, racemic
      methamphetamine seems also to be on the market.

PMID- 30199818
TI  - Mitochondrial permeability transition pore contributes to mitochondrial
      dysfunction in fibroblasts of patients with sporadic Alzheimer's disease.
AB  - In the last few decades, many reports have suggested that mitochondrial function
      impairment is a hallmark of Alzheimer's disease (AD). Although AD is a
      neurodegenerative disorder, mitochondrial damage is also present in patients'
      peripheral tissues, suggesting a target to develop new biomarkers. Our previous
      findings indicate that AD fibroblasts show specific defects in mitochondrial
      dynamics and bioenergetics, which affects the generation of adenosine
      triphosphate (ATP). Therefore, we explored the possible mechanisms involved in
      this mitochondrial failure. We found that compared with normal fibroblasts, AD
      fibroblasts had mitochondrial calcium dysregulation. Further, AD fibroblasts
      showed a persistent activation of the non-specific mitochondrial calcium channel,
      the mitochondrial permeability transition pore (mPTP). Moreover, the
      pharmacological blockage of mPTP with Cyclosporine A (CsA) prevented the increase
      of mitochondrial superoxide levels, and significantly improved mitochondrial and
      cytosolic calcium dysregulation in AD fibroblasts. Finally, despite the failure
      of CsA to improve ATP levels, the inhibition of mitochondrial calcium uptake by
      the mitochondrial calcium uniporter increased ATP production in AD fibroblasts,
      indicating that these two mechanisms may contribute to mitochondrial failure in
      AD fibroblasts. These findings suggest that peripheral cells present similar
      signs of mitochondrial dysfunction observed in the brain of AD patients.
      Therefore, our work creates possibilities of new targets to study for early
      diagnosis of the AD.

PMID- 30199821
TI  - Microclimate: A critical review in the context of pressure ulcer prevention.
AB  - Pressure ulcers are caused by sustained mechanical loading and deformation of the
      skin and subcutaneous layers between internal stiff anatomical structures and
      external surfaces or devices. In addition, the skin microclimate (temperature,
      humidity and airflow next to the skin surface) is an indirect pressure ulcer risk
      factor. Temperature and humidity affect the structure and function of the skin
      increasing or lowering possible damage thresholds for the skin and underlying
      soft tissues. From a pressure ulcer prevention research perspective, the effects
      of humidity and temperature next to the skin surface are inextricably linked to
      concurrent soft tissue deformation. Direct clinical evidence supporting the
      association between microclimate and pressure ulceration is sparse and of high
      risk of bias. Currently, it is recommended to keep the skin dry and cool and/or
      to allow recovery periods between phases of occlusion. The stratum corneum must
      be prevented from becoming overhydrated or from drying out but exact ranges of an
      acceptable microclimate are unknown. Therefore, vague terms like 'microclimate
      management' should be avoided but product and microclimate characteristics should
      be explicitly stated to allow an informed decision making. Pressure ulcer
      prevention interventions like repositioning, the use of special support surfaces,
      cushions, and prophylactic dressings are effective only if they reduce sustained
      deformations in soft tissues. This mode of action outweighs possible undesirable
      microclimate properties. As long as uncertainty exists efforts must be taken to
      use as less occlusive materials as possible. There seems to be individual
      intrinsic characteristics making patients more vulnerable to microclimate
      effects.

PMID- 30199820
TI  - Estrogen-related seizure exacerbation following hormone therapy for assisted
      reproduction in women with epilepsy.
AB  - PURPOSE: Exogenous estrogens might lead to seizure worsening in women with
      epilepsy (WWE) by lowering the seizure threshold and inducing glucuronidation in
      women taking lamotrigine. Assisted reproduction techniques are increasingly used
      and often require estrogenic and estrogen raising hormone therapy. We aimed at
      reporting their possible impact on seizures in WWE. METHODS: We describe two
      cases of seizure exacerbation following hormone therapy for assisted reproduction
      in WWE. RESULTS: Patient 1: 46 years old woman, with right temporal dysplasia. At
      40 years she had monthly focal seizures, possibly progressing to bilateral tonic
      clonic seizures, she took levetiracetam 3000/day and she underwent gonadotropin
      therapy for ovarian stimulation. Estrogen blood levels showed a sudden and
      significant rise, up to 1019 pg/ml and she had a concomitant cluster of three
      tonic-clonic seizures in 24 h. Patient 2: 41 years old woman with focal epilepsy
      of unknown etiology. At 38 years she was taking lamotrigine 450 mg/day and had
      been seizure free for three years. She took estradiol valerate 4 mg for 10 days
      for endometrial preparation for embryo transfer and had the only seizure over six
      years, with the exception of auras during advanced pregnancy, related to marked
      decrease of lamotrigine blood levels. During adjunctive concomitant therapy with
      clobazam, neither patient had seizures while on hormone therapy. CONCLUSIONS: Our
      data suggest that hormone therapy for assisted reproduction could exacerbate
      seizures and should be carefully monitored in WWE, especially those taking drugs
      inactivated by glucuronidation. Adjunctive concomitant antiepileptic therapy
      should be considered.

PMID- 30199822
TI  - Co-activation is not altered in the contra-lateral limb of individuals with
      moderate knee osteoarthritis compared to healthy controls.
AB  - BACKGROUND: Contra-lateral knee joint function in individuals with moderate knee
      osteoarthritis is not well understood, despite the functional burden of bilateral
      osteoarthritis on end stage clinical management. The purpose of this study was to
      determine whether co-activation and joint biomechanics are altered in the contra
      lateral limb compared to age-matched controls. METHODS: 20 Individuals with
      moderate knee osteoarthritis and 20 asymptomatic individuals walked on an
      instrumented dual belt treadmill at a self-selected speed. Surface
      electromyography of the knee joint musculature, including quadriceps, hamstrings
      and gastrocnemius muscles, normalized to maximum voluntary isometric
      contractions, as well as sagittal plane motion and sagittal and frontal plane
      moments were collected. Co-contraction indices were calculated and discrete
      variables from motion and moment data were extracted. Two-sample t-tests and 2
      sample mixed model ANOVAs were performed with alpha <0.05. FINDINGS: Contra
      lateral knee muscle co-activation differences were not found between groups (p >
      0.65). Peak knee adduction moment (0.41 Nm/kg vs. 0.32 Nm/kg) and knee adduction
      moment impulse (0.14 Nm s/kg vs. 0.10 Nm s/kg) were higher in the contra-lateral
      limb compared to the asymptomatic group respectively, whereas the sagittal motion
      (9.8 degrees  vs. 14.4 degrees ) and moment ranges (0.66 Nm/kg vs. 0.86 Nm/kg)
      during stance were less dynamic (p < 0.03). INTERPRETATION: The contra-lateral
      limb was functioning differently biomechanically despite no changes present in
      muscle co-activation. Findings suggest biomechanical changes are occurring
      without greater demand on the neuromuscular system to preserve contra-lateral
      joint function in moderate knee osteoarthritis gait. A greater focus should be
      made to address biomechanical abnormalities in both knees of individuals with
      moderate unilateral symptomatic knee osteoarthritis.

PMID- 30199823
TI  - Techno-economic analysis of geopolymer production from the coal fly ash with high
      iron oxide and calcium oxide contents.
AB  - In this work, we firstly examined the technical feasibility of geopolymer
      synthesis from the coal fly ash with high iron oxide (48.84 wt.%) and calcium
      oxide (22.15 wt.%) contents. The heat resistance of geopolymer was represented by
      the dry weight loss which ranged from 2.5 to 4.9% and was better than that
      (11.7%) of OPC. However, the high iron oxide content made the acid resistance (13
      14%) of geopolymer inferior to OPC. The economics of geopolymer production
      changes significantly upon the variation in the arrangement of material use and
      geopolymer price. The costs of Na2SiO3 and NaOH and the benefit of geopolymer
      selling were the major factors affecting the economic feasibility of geopolymer
      production. When the Na2SiO3 price was around 400 USD/ton, the geopolymer
      production will be profitable even if the geopolymer price was as low as 50
      USD/ton. It is possible to improve the economics of geopolymer production by
      varying the arrangement of material use while not impairing the performance of
      geopolymer.

PMID- 30199819
TI  - Cx26 partial loss causes accelerated presbycusis by redox imbalance and
      dysregulation of Nfr2 pathway.
AB  - Mutations in GJB2, the gene that encodes connexin 26 (Cx26), are the most common
      cause of sensorineural hearing impairment. The truncating variant 35delG, which
      determines a complete loss of Cx26 protein function, is the prevalent GJB2
      mutation in several populations. Here, we generated and analyzed Gjb2+/- mice as
      a model of heterozygous human carriers of 35delG. Compared to control mice,
      auditory brainstem responses (ABRs) and distortion product otoacoustic emissions
      (DPOAEs) worsened over time more rapidly in Gjb2+/- mice, indicating they were
      affected by accelerated age-related hearing loss (ARHL), or presbycusis. We
      linked causally the auditory phenotype of Gjb2+/- mice to apoptosis and oxidative
      damage in the cochlear duct, reduced release of glutathione from connexin
      hemichannels, decreased nutrient delivery to the sensory epithelium via cochlear
      gap junctions and deregulated expression of genes that are under transcriptional
      control of the nuclear factor erythroid 2-related factor 2 (Nrf2), a pivotal
      regulator of tolerance to redox stress. Moreover, a statistically significant
      genome-wide association with two genes (PRKCE and TGFB1) related to the Nrf2
      pathway (p-value < 4 * 10-2) was detected in a very large cohort of 4091
      individuals, originating from Europe, Caucasus and Central Asia, with hearing
      phenotype (including 1076 presbycusis patients and 1290 healthy matched
      controls). We conclude that (i) elements of the Nrf2 pathway are essential for
      hearing maintenance and (ii) their dysfunction may play an important role in the
      etiopathogenesis of human presbycusis.

PMID- 30199824
TI  - Construction of 2D heterojunction system with enhanced photocatalytic
      performance: Plasmonic Bi and reduced graphene oxide co-modified Bi5O7I with high
      speed charge transfer channels.
AB  - The efficient electron-hole charge pair separation, ultra-fast electron migration
      and excellent light harvest capacity are essential for semiconductor
      photocatalyst with superior photocatalytic performance. In this study, we
      constructed layered 2D/2D heterojunction composite of Bi@Bi5O7I/rGO (BiBGOI)
      through a facile surface charge mediated self-assembly strategy. The unique 2D/2D
      heterostructure with face to face contact can increase the contact area and
      generate a large amount of charge transfer nanochannels in the interfacial
      heterojunction, resulting in the enhancement of photocatalytic activity. Addition
      of semimetal Bi can enhance light absorption, and the local electromagnetic field
      dominated by SPR effect is favorable for photoinduced charge pair separation. The
      novel composite showed superior photocatalytic performance for decomposing
      levofloxacin (LVFX), which was attributed to the unique 2D/2D structure and SPR
      effect. The enhanced mineralization ability of the novel composite was ascribed
      to the strong oxidization ability of photoinduced holes, further evaluating high
      charge pair separation efficiency. In addition, the strong adsorption capacity of
      rGO for LVFX molecules can enable active radicals transfer into the surface to
      decompose it. This work will shed light on constructing 2D/2D heterojunction
      system assisted with SPR effect for the practical application in removal of
      organic pollutants.

PMID- 30199825
TI  - Improved peroxidase-mediated biodegradation of toluene vapors in the moving-bed
      activated sludge diffusion (MASD) process using biosurfactant-generating biomass
      stimulated with H2O2.
AB  - Two strategies were attempted to improve the biodegradation and mineralization of
      toluene vapors in the activated sludge diffusion (ASD) process using
      biosurfactant-generating Pseudomonas spp. and Bacillus spp. mixture. Different
      operational parameters including toluene concentration, superficial air velocity,
      biomass concentration, moving-media insertion and H2O2 were evaluated on toluene
      removal in the ASD process within 550 days of operation. It was found that
      complete biodegradation and 79.8% mineralization of toluene vapors at inlet
      loading rate of 144 g/m3.h could be achieved in the ASD process by inserting
      moving media (MASD) at a volume ratio of 20% along with stimulation of bacteria
      with H2O2. The concentration of biosurfactant and peroxidase generated in the
      integrated process (H2O2-stimulated MASD reactor) was 3.7 and 2.5 times of that
      in the conventional ASD process. The maximum toluene elimination capacity
      obtained in the H2O2- stimulated MASD process was 285 g/m3.h at an inlet loading
      rate of around 430 g/m3.h. Accordingly, H2O2-mediated MASD process could be a
      promising technique for efficient biodegradation and mineralization of aromatic
      hydrocarbons in the contaminated air streams.

PMID- 30199826
TI  - Effect of sewage sludge composition on the susceptibility to spontaneous
      combustion.
AB  - The different technologies applied to the sewage sludge management have in common
      a first step devoted to the storage. In the case of dried sludges, this storage
      leads to important safety concerns because of the explosive character of the
      resulting dusts. In order to ensure safety in the storage step, it is necessary
      to evaluate the spontaneous combustion trends on terms of measurable chemical and
      physical properties of the dried sludges. In order to accomplish this scope,
      twelve samples from different wastewater treatment plants were characterized,
      correlating the susceptibility to spontaneous combustion with both the sludge
      composition and the heating value. Equations traditionally used for coals were
      used to determine the higher heating value from the chemical composition, finding
      as main source of error the high oxygen content of the sludge samples. Concerning
      the thermal susceptibility, different parameters were obtained (Maciejasz Index,
      induction temperature, maximum weight loss temperature, characteristic
      temperature and activation energy), being in all cases the spontaneous
      combustions favored by high H/C and low O/C ratios. Likewise, the presence of
      sulphur in the dried sludge was found to increase the thermal susceptibility of
      the material. This effect is tentatively explained with the formation of
      pyrophoric iron sulfides.

PMID- 30199827
TI  - Designing iron carbide embedded isolated boron (B) and nitrogen (N) atoms co
      doped porous carbon fibers networks with tiny amount of BN bonds as high
      efficiency oxygen reduction reaction catalysts.
AB  - In this paper, polyvinylpyrrolidone (PVP) and 4-hydroxybenzeneboronic acid (o
      HPBA) are polarized in alkaline solution and then employed as boron (B) and
      nitrogen (N) sources. Fe(AC)2/o-HPBA/PVP/DMF(N,N-Dimethylformamide) slurries are
      first electrospunned into three-dimensional (3D) networks. Due to the
      electrostatic repulsion between negatively charged O- groups surrounding N and B
      atoms, N and B atoms can be kept far away from each other. Upon optimizing o-HPBA
      dosages, the maximum amount of isolated B and N atoms are successfully doped into
      the 3D porous iron carbide (Fe3C) embedded B and N co-doped carbon fibers
      (Fe3C@B1.0NPCFs) networks with tiny BN clusters. Electrochemical measure results
      demonstrate that Fe3C@B1.0NPCFs exhibit much better oxygen reduction reaction
      (ORR) activity than 20 wt% Pt/C in alkaline electrolyte. In acidic electrolyte,
      Fe3C@B1.0NPCFs also displays ORR activity comparable to Pt/C (its onset and half
      wave potentials are just 40 and 50 mV more negative than those of Pt/C).
      Moreover, Fe3C@B1.0NPCFs show better stability and methanol tolerance ability
      than Pt/C for ORR in both alkaline and acidic solutions. This work opens new
      avenues for intentionally preventing the malignant combination of B and N atoms
      and boosting the electrocatalytic activity of B and N co-doped and Fe3C embedded
      carbon catalysts.

PMID- 30199828
TI  - Evaluating the potential of superhydrophobic nanoporous alumina membranes for
      direct contact membrane distillation.
AB  - HYPOTHESIS: Direct contact membrane distillation (DCMD) processes exploit water
      repellant membranes to desalt warm seawaters by allowing only water vapor to
      transport across. While perfluorinated membranes/coatings are routinely used for
      DCMD, their vulnerability to abrasion, heat, and harsh chemicals necessitates
      alternatives, such as ceramics. Herein, we systematically assess the potential of
      ceramic membranes consisting of anodized aluminum oxide (AAO) for DCMD.
      EXPERIMENTS: We rendered AAO membranes superhydrophobic to accomplish the
      separation of hot salty water (343 K, 0.7 M NaCl) and cold deionized water (292
      K) and quantified vapor transport. We also developed a multiscale model based on
      computational fluid dynamics, conjugate heat transfer, and the kinetic theory of
      gases to gain insights into our experiments. FINDINGS: The average vapor fluxes,
      J, across three sets of AAO membranes with average nanochannel diameters (and
      porosities) centered at 80 nm (32%), 100 nm (37%), and 160 nm (57%) varied by <
      25%, while we had expected them to scale with the porosities. Our multiscale
      simulations unveiled how the high thermal conductivity of the AAO membranes
      reduced the effective temperature drive for the mass transfer. Our results
      highlight the limitations of AAO membranes for DCMD and might advance the
      rational development of desalination membranes.

PMID- 30199829
TI  - In situ synthesis of tin dioxide submicrorods anchored on nickel foam as an
      additive-free anode for high performance sodium-ion batteries.
AB  - A hybrid of tin dioxide submicrorods anchored on conductive nickel foam (SnO2
      submicrorods-Ni foam) is in-situ synthesized via a hydrothermal and a subsequent
      heat treatment by using stannic chloride and sodium hydroxide as the starting
      materials. Characterization results indicate that the synthesized SnO2
      submicrorods has a length of ~400 nm and a diameter of ~150 nm anchoring tightly
      on Ni foam. The electrochemical properties of the material as an additive-free
      anode for sodium-ion batteries are investigated. And a comparative research of
      the reversible sodium storage properties between the additive-free electrode of
      SnO2 submicrorods-Ni foam and the additive electrode of SnO2 rod-assembly
      microspheres is carried out. The results demonstrate that the SnO2 submicrorods
      Ni foam is a highly attractive anode for sodium ion batteries, which could
      exhibit much better sodium storage properties than the SnO2 rod-assembly
      microspheres and other reported SnO2-based additive electrodes. The excellent
      sodium storage properties of the SnO2 submicrorods-Ni foam electrode can be
      attributed to its structure advantages without additive-assistant, which increase
      sodium storage active sites, facilitate the electronic/ionic transport and
      stabilize the total electrode structure during charge-discharge process.

PMID- 30199830
TI  - Functional food packaging for reducing residual liquid food: Thermo-resistant
      edible super-hydrophobic coating from coffee and beeswax.
AB  - Edible super-hydrophobic coatings have attracted great attentions as they can
      avoid the waste of liquid foods, such as honey and milk, adhered to the inside of
      containers. However, the poor thermal stabilities of edible super-hydrophobic
      coatings restrict their applications. In this work, a thermo-resistant edible
      super-hydrophobic coating has been fabricated using beeswax and coffee, which are
      approved by U.S. Food and Drug Administration. This coating surface has the
      similar micro/nanoscale structure to that of the leaf surface. A variety of
      liquid foods can freely roll on this coating surface in spherical. This special
      wetting property effectively reduces the residue of liquid foods, when they are
      poured out of the containers. With the introduction of coffee lignin, the thermal
      stability and adhesive force of the coating increases significantly. The apparent
      contact angle of this coating can remain to be above 150 degrees  after a long
      time heating and flushing. This thermo-resistant edible super-hydrophobic coating
      can solve the problem that original edible super-hydrophobic coating is not
      resistant to high temperature, and has a broad application prospect in the field
      of functional food packaging.

PMID- 30199831
TI  - Ti/PbO2-Sm2O3 composite based electrode for highly efficient electrocatalytic
      degradation of alizarin yellow R.
AB  - In this work, a novel Ti/PbO2-Sm2O3 composite electrode with high
      electrocatalytic activity is successfully fabricated via simple electrodeposition
      method and further investigated for electrochemical degradation of alizarin
      yellow R (AYR) wastewater. The test results of X-ray diffraction, field-emission
      scanning electron microscopy and energy-dispersive X-ray spectroscopy confirm
      that Sm2O3 is successfully composited with PbO2. The coating of Ti/PbO2-Sm2O3
      composite electrode stacked by typical pyramid-like micro-particles exhibits
      smooth and compact surface morphology which is conducive to enhancing the
      corrosion resistance of electrode. Furthermore, electrochemical performance tests
      indicate that Ti/PbO2-Sm2O3 composite electrode has advantages of higher oxygen
      evolution potential, lower charge transfer resistance and longer lifetime over
      Ti/PbO2 electrode. Electrolyte concentration, plate space, initial pH and cell
      voltage are assessed to optimize the degradation condition of AYR. The results
      show that COD removal efficiency and degradation efficiency of AYR on Ti/PbO2
      Sm2O3 composite electrode reach up to 79.90% and 80.00% under the optimal
      conditions (Na2SO4 electrolyte concentration 9.0 g L-1, plate space 3.0 cm,
      initial pH 5, cell voltage 3.0 V and electrolysis time 150 min), respectively.
      The degradation of AYR follows pseudo-first-order reaction kinetics, and a
      plausible mineralization pathway of AYR is proposed on the basis of the
      identification of major intermediate products. These results suggest that Ti/PbO2
      Sm2O3 composite electrode is a promising candidate for electrocatalytic
      degradation of AYR wastewater.

PMID- 30199832
TI  - The role of the central metal ion of ethane-bridged bis-porphyrins in histidine
      sensing.
AB  - Ethane-bridged bis-porphyrin derivatives are reported for the selective detection
      of various analytes in sensing applications. The central metal ion is able to
      rule specific molecular arrangements upon analyte binding. Three bis-porphyrin
      compounds: a free base (metal free), Ni complex, and Cu complex, have been tested
      for histidine detection in aqueous media. Histidine is involved in various
      biological processes, including such deadly disease as lung cancer. The
      conformational changes of bis-porphyrins, induced by histidine binding, can be
      detected by monitoring the Soret band position. The spectroscopic
      characterization, at the air-water subphase interface, indicates that, in the
      presence of histidine, the Ni and Cu metallated derivatives undergo
      conformational changes. This behaviour was confirmed when these two derivatives
      were deposited onto the solid support by Langmuir-Schaefer (LS) technique. A
      prototypal Surface Plasmon Resonance (SPR) detection system for histidine based
      on these two porphyrin LS films was developed. The Cu substituted compound based
      SPR system allows the histidine sensing down to nanomolar concentration.
      Furthermore, a SPR response of the Ni bis-porphyrin shows a semilogarithmic
      dependence on the histidine concentration up to 10-6 M proposing the use of these
      two porphyrins in a sensor array for the monitoring of histidine levels in
      plasma.

PMID- 30199833
TI  - Uniform trend in layer-by-layer deposition of heteropolytungstates.
AB  - HYPOTHESIS: The layer-by-layer deposition of films including polyoxometalates
      (POMs) results in a very interesting range of applications in various fields such
      as electrochemical devices and as photochromic coatings. However, the fundamental
      knowledge of the parameters responsible for tuning the properties of the film
      (i.e. relation between the structure and composition of the POM and the
      properties of the final film) is still lacking. EXPERIMENTS: The current work
      establishes the relationship between the film thickness, the quantity of POM
      incorporated in each layer and the electrochemical response of the (PAH-POM)x
      coatings, where PAH is poly(allylamine hydrochloride). FINDINGS: The results
      presented in this work show that the film thickness, composition and
      electrochemical activity scale proportionally with the number of W atoms in a
      series of heteropolytungstates ranging from 5 to 48 (P2W5, PW12, P2V3W15, P2W18,
      P5W30, P8W48). The obtained results allow us to establish a method to predict the
      behavior as well as the properties of the film based on the nature of the POM
      used.

PMID- 30199834
TI  - The influence of group values and behavior on adolescent male perceptions of and
      use of homophobic language.
AB  - INTRODUCTION: The pervasive and derogatory use of homophobic language is a threat
      to safe, respectful, and inclusive school environments. Group membership has been
      shown to influence how students use homophobic language. Previous qualitative
      studies have largely approached the use of this language from the theoretical
      framework of hegemonic masculinity. In contrast, the current study actively
      challenged all assumptions about the use of this language. METHOD: This study was
      conducted in a public high school located in a rural conservative Christian
      community in the Intermountain West (USA). Using hermeneutic qualitative
      methodology to assess individual perceptions of homophobic language, 20 randomly
      selected 12th-grade male students (17-18 years of age) were individually
      interviewed. RESULTS: Three distinct groups emerged during our interviews:
      students on the debate team, students who strongly identified with a conservative
      religion, and students on popular athletic teams. Membership in specific peer
      groups influenced how students participated in or abstained from using homophobic
      language. Contrary to the prevailing research that pairs religiosity with
      negatively biased attitudes toward LGBTQIA, in this study, participants'
      religious beliefs appeared to be associated with respecting others' feelings and
      a decreased likelihood of using homophobic language. CONCLUSIONS: After
      summarizing this study's findings, we conclude with implications for practice. To
      more effectively deter the use of homophobic language, we encourage school-based
      interventions that target specific groups of adolescents and consider the social
      context in which homophobic language occurs.

PMID- 30199835
TI  - Combining human STR and microbial population profiling: Two case reports.
AB  - In forensic case investigations involving human traces, cell type identification
      has become increasingly important. No longer only the donor of a trace (sub
      source level), but also the actions which could have led to the deposition of the
      trace ('beyond-the-source'/activity level) need to be evaluated by forensic
      experts. For this evaluation determining the cellular source of a DNA profile can
      be beneficial. In this report two criminal cases are described where both human
      STR profiling and microbial population profiling were applied to the same trace
      sample. Human STR profiling was used to evaluate the sub-source question and
      microbial population profiling was used to evaluate the source question. The
      Bayesian framework was used to evaluate the evidence.

PMID- 30199836
TI  - Effect of compliant layers within piezoelectric composites on power generation
      providing electrical stimulation in low frequency applications.
AB  - For patients that use tobacco or have diabetes, bone healing after orthopedic
      procedures is challenging. Direct current electrical stimulation has shown
      success clinically to significantly improve bone healing in these difficult-to
      fuse populations. Energy harvesting with piezoelectric material has gained
      popularity in the last decade, but is challenging at low frequencies due to
      material properties that limit total power generation at these frequencies.
      Stacked generators have been used to increase power generation at lower voltage
      levels but have not been widely explored as a load-bearing biomaterial to provide
      DC stimulation. To match structural compliance levels and increase efficiency of
      power generation at low frequencies, the effect of compliant layers between
      piezoelectric discs was investigated. Compliant Layer Adaptive Composite Stacks
      (CLACS) were manufactured using five PZT discs connected electrically in parallel
      and stacked mechanically in series with a layer of low modulus epoxy between each
      disc. The stacks were encapsulated, keeping PZT and overall volume constant. Each
      stack was electromechanically tested by varying load, frequency, and resistance.
      As compliant layer thickness increased, power generation increased significantly
      across all loads, frequencies, and resistances measured. As expected, increase in
      frequency significantly increased power output for all groups. Similarly, an
      increase applied peak-to-peak mechanical load also significantly increased power
      output. The novel use of CLACS for power generation under load and frequencies
      experienced by typical orthopedic implants could provide an effective method to
      harvest energy and provide power without the use of a battery in multiple low
      frequency applications.

PMID- 30199837
TI  - Design of a surrogate for evaluation of methods to predict bone bending
      stiffness.
AB  - The high incidence of osteoporosis and related fractures demands for the use and
      development of methods capable of detecting changes in bone mechanical
      properties. The most common clinical and laboratory methods used to detect
      changes in bone mechanical properties, such as stiffness, strength, or flexural
      rigidity, include: mechanical testing, medical imaging, medical image-based
      analytical calculations, and medical image-based finite element analysis.
      However, the innate complexity of bone makes validation of the results from each
      method difficult. The current study presents the design, fabrication, and
      functional testing of a bi-material and computed tomography scan compatible bone
      surrogate which provides consistent reproducible mechanical properties for
      methodological evaluation of experimental, analytical, and computational bone
      bending stiffness prediction methods.

PMID- 30199838
TI  - Origin of low Young modulus of multicomponent, biomedical Ti alloys - Seeking
      optimal elastic properties through a first principles investigation.
AB  - Multicomponent, biomedical beta-Ti alloys offer ultra-low Young modulus values
      that are related to a unique and poorly understood reduction of C44 and C'
      elastic constants in comparison with binary systems. The elastic properties of
      such materials are difficult to control due to the large variations occurring
      even for a small change in chemical composition, which cannot be explained using
      existing theories. In this article, we investigate the above issues through
      systematic ab initio elastic constants calculations for a series of binary,
      ternary and quaternary Ti alloys. Special attention is paid to examining the
      reliability of the methodology adopted and to clarifying the atomic scale
      mechanisms that affect the mechanical properties of the systems analysed. It was
      found that the lower boundary of the polycrystalline Young modulus of Ti-Nb-base
      beta phase is close to 50 GPa, and strongly depends on two specific electronic
      hybridisations related to niobium and simple metals addition that control C44 and
      C'. Based on the relationship established between electronic structure and
      mechanical properties, we propose several quaternary alloys whose directional
      <100> Young modulus values are equal or similar to that of human bones. Some
      electronic-based guidelines for designing new multicomponent beta-Ti alloys are
      also formulated.

PMID- 30199839
TI  - Effects of multiple firings on mechanical properties and resin bonding of lithium
      disilicate glass-ceramic.
AB  - OBJECTIVES: This study aimed to evaluate the effects of different firing cycles
      on surface hardness, fracture toughness, and roughness of lithium disilicate
      glass-ceramic, as well as their bond strength to resin. MATERIALS AND METHODS: A
      total of 320 polished lithium disilicate glass-ceramic plates were assigned to
      four main groups (n = 60) to receive one, two, three, or four firing cycles,
      respectively. Ceramic plates of the four groups were conditioned with HF acid
      followed by silanization. The pre-treated ceramic plates were cemented with
      composite resin cylinders using conventional or self-adhesive resin cements to
      build bonded specimens, and submitted to shear-bond-strength (SBS) testing after
      water storage for 24 h or 3 mo at 37  degrees C. The ceramic received different
      firing cycles after polishing or HF etching was observed using a scanning
      electron microscope, and their surface roughnesses were determined by a
      profilometer. The surface Vickers hardness, fracture toughness, and related
      Weibull analysis results of the polished ceramics after undergoing different
      firing-cycle times were compared. RESULTS: One sintering significantly increased
      fracture toughness of lithium disilicate glass-ceramic; however, multiple firing
      cycles failed to increase it further. Weibull analysis revealed a significant
      difference in terms of structural reliability among the specimens receiving 0-4
      firing cycles. Specimens that received no firing cycle showed the highest surface
      hardness. Multiple firing cycles had no significant influence on the surface
      Vickers hardness and surface roughness. HF etching increased surface roughness,
      and the roughened surface improved the resin SBS of lithium disilicate glass
      ceramic. Multiple firing cycles had no significant effect on surface roughness.
      Furthermore, multiple firing cycles and 3-mo water storage had no significant
      effect on the SBS. CONCLUSIONS: The mechanical properties of lithium disilicate
      glass-ceramics would be partially affected by multiple firing cycles, while their
      resin bonding would not be.

PMID- 30199840
TI  - Perceptions of sense of community and community engagement among rural nurses:
      Results of a national survey.
AB  - BACKGROUND: Variations in rural nurses' sense of community and engagement in
      rural communities are poorly understood, although there is evidence that these
      are linked to community cohesion and perceived community resilience. OBJECTIVE:
      The aim of our research was to develop descriptive profiles of rural nurses who
      exhibit a sense of community and community engagement at low, average, and high
      levels, based on occupational, personal, community, and regional characteristics.
      These results were linked to levels of cohesion and resilience. DESIGN: A survey
      questionnaire, including established scales, demographic information, and
      information about rural nursing practice was administered to rural nurses.
      SETTINGS: Rural communities in all provinces and territories in Canada outside
      the commuting zone of urban areas with 10,000 or more inhabitants. PARTICIPANTS:
      Multi-level systematic stratified sampling was employed for the national survey.
      A subsample of 2116 Registered Nurses, Nurse Practitioners, and Licensed
      Practical Nurses comprised the participants for this analysis. METHODS: The
      analysis was conducted in two stages: (1) in the first subset, those (n = 2116)
      whose primary work community was rural, remote, or rurban with less than 10,000
      inhabitants were grouped into a nine-group typology based on low, average, and
      high tertiles of Psychological Sense of Community and Community Engagement. The
      second subset (n = 993) represented those in three groups: low-low, average
      average, and high-high scores on the two indices. Significant differences between
      the three groups were identified based on occupational, personal, community, and
      regional characteristics. Chi Square, ANOVA, and correlation tests were applied
      as required. RESULTS: Nurses with low scores on both Psychological Sense of
      Community and Community Engagement were more likely to be from larger
      communities, single or divorced and living and working in the North. Those with
      average scores on both scales have been in their nursing positions for more than
      20 years, are middle aged and are satisfied with their home community. Nurses in
      the third group have high scores on both indicators; they are more likely to be
      from a smaller childhood communities, married or living common-law, and are in
      the late middle age group. CONCLUSIONS: By focusing on the key variables or
      traits of nurses, modifiable recruitment and retention practices can be
      implemented. For example, it is important to recruit nurses who are from smaller
      communities. Other initiatives for nurses include matching community activities
      with the age and stage of the family and developing a welcoming strategy for the
      workplace and community for newly arrived nurses.

PMID- 30199841
TI  - Multi-targeted dihydrazones as potent biotherapeutics.
AB  - Hydrazone compounds were considered as a useful moiety in drug design
      development. Therefore, these studies were aimed at the synthesis of new
      dihydrazones and were screened for their in vitro H+/K+-ATPase and anti
      inflammatory activities. The results revealed that compounds 9 (22 +/- 0.62
      ug/mL), 10 (26 +/- 0.91 ug/mL), 15 (24 +/- 0.44 ug/mL), 16 (28 +/- 0.63 ug/mL),
      17 (12 +/- 0.38 ug/mL), 18 (14 +/- 0.47 ug/mL), 19 (26 +/- 0.54 ug/mL), 20 (16 +/
      0.41 ug/mL), 25 (06 +/- 0.68 ug/mL) and 26 (08 +/- 0.43 ug/mL) showed excellent
      H+/K+-ATPase activity and their IC50 value were lower than the standard drug
      Omerazole (48 +/- 0.12 ug/mL). Compounds 5 (28 +/- 0.65 ug/mL), 6 (24 +/- 0.61
      ug/mL), 7 (28 +/- 0.64 ug/mL), 8 (26 +/- 0.45 ug/mL), 11 (30 +/- 0.74 ug/mL), 12
      (28 +/- 0.40 ug/mL), 13 (32 +/- 0.24 ug/mL), 14 (30 +/- 0.55 ug/mL) and 21 (08 +/
      0.47 ug/mL), 22 (12 +/- 0.47 ug/mL), 23 (10 +/- 0.51 ug/mL) and 24 (14 +/- 0.84
      ug/mL) showed better anti-inflammatory activity compared to standard indomethacin
      (44 +/- 0.15 ug/mL). The structure activity relationship (SAR) showed that,
      electron donating groups (OH, OCH3) favored the H+/K+-ATPase and antioxidants
      activity, whereas, electron withdrawing groups (F, Cl, Br and NO2) favored the
      anti-inflammatory activity. Furthermore, molecular docking study was performed to
      investigate the binding interactions of the most active analogs with the active
      site of H+/K+-ATPase enzyme. Compounds 25 (G-score = -9.063) and 26 (G-score = 
      8.977) showed the highest docking G-scores for H+/K+-ATPase inhibition activity.

PMID- 30199842
TI  - Cytotoxic withanolides from the aerial parts of Tubocapsicum anomalum.
AB  - Ten new withanolides (1-10) and three artificial withanolides (11-13) were
      isolated from the aerial parts of Tubocapsicum anomalum, together with five known
      analogues (14-18). Their structures were determined on the basis of extensive
      spectroscopic and chemical methods. They include seven acnistin-type (1-4, 11, 14
      and 15), three withajardin-type (5-7), and eight normal-type (8-10, 12, 13 and 16
      18) withanolides. Of normal-type withanolides, a chemical conversion from the
      16alpha,17alpha-epoxywithanolide (16) to Delta13,14-16alpha-hydroxywithanolide
      (18) was achieved by Wagner-Meerwein rearrangement. All isolates were evaluated
      for their cytotoxicity against four human tumor cell lines (HCT-116, HepG2, MCF-7
      and A375). Among them, compounds 1-3, 6-8, 14, 16-18 showed cytotoxic activity
      with IC50 values of 0.24-8.71 MUM.

PMID- 30199843
TI  - Fluid volume, fluid balance and patient outcome in severe sepsis and septic
      shock: A systematic review.
AB  - PURPOSE: This systematic review and meta-analysis was conducted to evaluate the
      mortality risk in severe sepsis and septic shock with a low and high fluid
      volume/balance. METHODS: Cohort studies that compared the mortality of patients
      with low or high fluid volume/balance were included. Electronic databases:
      PubMed/Medline PLUS, Embase, Scopus, and Web of Science were searched. Patient
      mortality at the longest follow-up was the primary outcome measure. The data were
      analyzed using STATA 14 statistical software. RESULTS: The current study included
      fifteen studies with 31,443 severe sepsis and/or septic shock patients. Patients
      with a high fluid balance have a 70% increased risk of mortality (pooled RR:
      1.70; CI: 1.20, 2.41; P = .003). Survivors of severe sepsis and/or septic shock
      received higher fluid volume in the first three hours. However, fluid volume
      administered in the first 24 h was higher for non-survivors. Low volume
      resuscitation in the first 24 h had a significant mortality reduction (P = .02).
      CONCLUSION: High fluid balance from the first 24 h to ICU discharge increases the
      risk of mortality in severe sepsis and/or septic shock. However, randomized
      clinical trials should be conducted to resolve the dilemma of fluid
      resuscitation.

PMID- 30199844
TI  - Association of exercise with smoking-related symptomatology, smoking behavior and
      impulsivity in men and women.
AB  - INTRODUCTION: Despite extensive efforts to develop effective smoking cessation
      interventions, 70-85% of American cigarette smokers who quit relapse within one
      year. Exercise has shown promise as an intervention; however, many results have
      been equivocal. This study explored how exercise is associated with smoking
      related symptomatology, smoking behavior and impulsivity in male and female
      smokers. METHODS: Participants were recruited throughout the United States using
      the on-line crowdsourcing platform, Amazon's Mechanical Turk. They completed a
      survey with self-report measures assessing exercise, smoking-related
      symptomatology, smoking behavior and impulsivity. Differences between men and
      women were tested using t- and chi-square tests. Regression analyses tested for
      associations between exercise and smoking-related symptomatology, smoking
      behavior and impulsivity. RESULTS: Participants (N = 604) were, on average, 32
      (SD = 6.2) years old, mostly Caucasian, with at least some college education and
      approximately half were women. Women exercised slightly less than men and had
      more negative affect, craving, physical symptoms and withdrawal. Women smoked
      more cigarettes per day, had greater nicotine dependency and more years of
      smoking. Positive affect was positively associated with exercise for both men and
      women; however, this association was significantly stronger in women. Negative
      affect and withdrawal were inversely associated with exercise for women only.
      Impulsivity was inversely associated with exercise for both men and women.
      CONCLUSION: Exercise was significantly associated with several smoking-related
      symptomatology, smoking behavior and impulsivity variables for both men and
      women, suggesting that exercise may be a useful intervention for smoking
      cessation. Future prospective research should determine how exercise directly
      impacts smoking cessation.

PMID- 30199845
TI  - The Villefranche Strombidium sulcatum: A review.
AB  - The marine oligotrich ciliate Strombidium sulcatum, the best known marine
      oligotrich of the marine microozoplankton, was first cultured in Villefranche-sur
      Mer 35 years ago. Cultures were maintained from 1983 to 2003 and used in 22
      studies investigating a very wide variety of questions. Here we review the major
      findings of these studies and underline their contributions to our knowledge of
      planktonic ciliate ecology and microbial ecology in general. We conclude with the
      observation that while ecophysiology has apparently fallen out of fashion,
      culture work will likely return as an invaluable resource in our present 'omics'
      era.

PMID- 30199846
TI  - Equine immunoglobulin F(ab')2 fragments protect mice from Rift Valley fever virus
      infection.
AB  - BACKGROUND: Rift Valley fever virus (RVFV) is an emerging arbovirus in Africa and
      the Arabian Peninsula, in which infection with RVFV poses a serious threat to
      humans and livestock globally. Approved treatments for RVFV infection, especially
      for use in humans, have not yet been developed. There is an urgent need for
      effective drugs to prevent RVFV disease. METHODS: In previous study, we developed
      RVFV virus like particles (VLPs) expressing the surface glycoproteins Gn and Gc.
      The morphology was shown to be similar to live RVFV under electron microscopy. In
      this study, we immunized horses with RVFV VLPs, prepared the immunoglobulin
      F(ab')2 fragments, and characterized its in vitro neutralization and in vivo
      efficacy in mice. RESULTS: F(ab')2 was found to potently neutralize RVFV in
      VeroE6 cells, and passive transfer of immunoglobulin F(ab')2 fragments resulting
      in reduced mortality in RVFV infected mice. CONCLUSION: Our results show that
      passive immunotherapy with equine immunoglobulin F(ab')2 fragments is a promising
      strategy to treat RVFV infections.

PMID- 30199847
TI  - Efficacy and safety of anti-interleukin-5 therapy in patients with asthma: A
      pairwise and Bayesian network meta-analysis.
AB  - INTRODUCTION: Anti-interleukin-5 therapy has been proposed as a novel and
      promising treatment option in asthma treatment. However, the optimum monoclonal
      antibodies for asthma treatment remain uncertain. METHODS: We searched the
      PubMed, EMBASE and Cochrane databases from their inceptions to June 2018 for
      randomized controlled trials that reported pulmonary function, adverse events,
      Asthma Quality of Life Questionnaire (AQLQ) scores, and asthmatic exacerbations
      resulting from anti-interleukin-5 therapy in asthma patients. Extracted data were
      analyzed by pairwise and network meta-analysis. RESULTS: Twenty-one randomized
      studies were identified for this analysis. By pairwise meta-analysis using a
      placebo as the reference, patients treated with monoclonal antibodies were
      associated with significantly improved forced expiratory volume (FEV1) values
      (standard mean difference [SMD], 0.18; 95% confidence interval [CI], 0.12-0.23; P
      < 0.001), lower rates of adverse events (risk ratio [RR], 0.93; 95% CI, 0.90
      0.97; P < 0.001) and significant improvements in the AQLQ scores (SMD, 0.20; 95%
      CI, 0.13-0.26; P < 0.001). There were no significant differences in exacerbations
      risks (RR, 0.68; 95% CI, 0.11-4.14; P = 0.097). According to network meta
      analysis, adverse events-related benefits were seen only with reslizumab, while
      AQLQ scores benefits, and pulmonary function benefits were still seen with all
      three monoclonal antibodies. The assessment of rank probabilities indicated that
      reslizumab presented the greatest likelihood of having benefits for pulmonary
      function, reducing adverse events and improving AQLQ scores when compared with
      the placebo, and mepolizumab presented the best benefits for reducing asthmatic
      exacerbations. CONCLUSIONS: Anti-interleukin-5 therapy appears to be a safe and
      effective treatment for asthma patients with respect to pulmonary lung function,
      adverse events and AQLQ scores, and do not increase asthmatic exacerbations. Our
      network meta-analysis in patients with asthma suggests that reducing adverse
      events benefits due to reslizumab, and pulmonary lung function benefits as well
      as good AQLQ scores are seen with respect to the three antibodies. Network meta
      analysis indicates the probability that the best anti-interlukin-5 therapy for
      asthma patients might be reslizumab, but further trials are required to determine
      the most effective asthma treatment drug.

PMID- 30199848
TI  - Improved RANKL production by memory B cells: A way for B cells promote alveolar
      bone destruction during periodontitis.
AB  - Periodontitis is a bacteria-induced disease that always clinically defined as
      loss of attachment, periodontal pocket and bone loss. Its mechanisms were
      considered to be complicated, involving an imbalance of the formation and
      resorption of bone. We sought to determine the function and mechanisms of the
      effects of B cells on osteoclastogenesis. We purified memory B cells from
      periodontitis or healthy animals and culture them. Receptor activator of nuclear
      factor kappa-B ligand (RANKL), expressed by gingival memory B cells, was detected
      by flow cytometry, enzyme-linked immunosorbent assay and real-time quantitative
      polymerase chain reaction (RT-qPCR). To discover any direct effects on
      osteoclastogenesis, gingival memory B cells were co-cultured with bone marrow
      mononuclear cells, osteoclast number and genes related to osteoclast
      differentiation were examined. In further investigations, an adoptive transfer
      experiment of memory B cells was designed, and pathologic indexes and expression
      of associated cytokines in different tissues were also investigated. We find that
      memory B cells from inflammatory gingiva produced more RANKL. Notably, such B
      cells promote osteoclastogenesis. In an adoptive transfer experiment, memory B
      cells enhanced alveolar bone loss and osteoclast formation. We also find a higher
      expression of RANKL, TNF-alpha, IL-1beta and IL-17A in gingival crevicular fluid,
      gingiva and cervical lymph nodes of adoptive transfer group. Our findings
      highlighted the considerable importance of B cells in alveolar bone homeostasis
      independent of antibody production during periodontitis.

PMID- 30199849
TI  - A pilot Indian family-based association study between dyslexia and Reelin pathway
      genes, DCDC2 and ROBO1, identifies modest association with a triallelic unit TAT
      in the gene RELN.
AB  - Dyslexia is a neurodevelopmental disorder that manifests as a reading disability
      despite normal intelligence and adequate educational opportunity. Twin and family
      studies have indicated a genetic component, while genome-wide studies have
      implicated a number of susceptibility genes, most of which have direct or
      indirect roles in neuronal migration. Reelin (RELN) has important biological
      functions facilitating migration of neurons. Polymorphisms in RELN have been
      implicated in related disorders like autism and schizophrenia but have not been
      examined in dyslexia. We hypothesized that not only RELN, but its interactors in
      the neuronal migration pathway may play roles in the etiology of dyslexia. Twenty
      two functional variants across six RELN signalling genes (RELN, VLDLR, APOER2,
      DAB1, LIS1 and NDEL1) and two dyslexia candidate genes (DCDC2 and ROBO1) were
      analyzed for association in twenty six nuclear and three extended families with
      individuals affected with dyslexia. Univariate association analysis was
      suggestive of association (puncorrected = 0.01) with rs362746 in RELN which
      however did not withstand Bonferroni corrections (pcorrected = 0.21). Multimarker
      tests indicated significant association (p = 0.037), based on which we tested for
      haplotype associations. Although there were no significant haplotypic
      associations, we found that a three marker unit with rs3808039 and rs2072403
      flanking and independently in linkage disequilibrium with rs362746 was
      significantly overtransmitted (risk allelic combination - TAT) to dyslexia
      affected individuals in the sample (p = 0.002). Our results suggest preliminary
      evidence for a new potential risk variant in the RELN locus for dyslexia.

PMID- 30199850
TI  - The 2018 Lasker~DeBakey Clinical Medical Research Award recognizes John Baird
      Glen for the discovery of propofol.

PMID- 30199851
TI  - RNA biologist Joan Steitz awarded the 2018 Lasker~Koshland Special Achievement
      prize.

PMID- 30199853
TI  - Focus/Summary.

PMID- 30199852
TI  - Michael Grunstein and David Allis receive the 2018 Lasker Basic Medical Research
      Award.

PMID- 30199855
TI  - Focus/Summary.

PMID- 30199854
TI  - Early Achievement of Blood Pressure Lowering and Hematoma Growth in Acute
      Intracerebral Hemorrhage: Stroke Acute Management with Urgent Risk-Factor
      Assessment and Improvement-Intracerebral Hemorrhage Study.
AB  - BACKGROUND: Previous studies have revealed that hematoma growth mainly occurs
      during the first 6 h after the onset of spontaneous intracerebral hemorrhage
      (ICH). Early lowering of blood pressure (BP) may be beneficial for preventing
      hematoma growth. However, relationships between timing of BP lowering and
      hematoma growth in ICH remain unclear. We investigated associations between
      timing of BP lowering and hematoma growth for ICH. METHODS: The Stroke Acute
      Management with Urgent Risk-factor Assessment and Improvement (SAMURAI)-ICH Study
      was a multicenter, prospective, observational study investigating the safety and
      feasibility of early (within 3 h from onset) reduction of systolic BP (SBP) to <
      160 mm Hg with intravenous nicardipine for acute hypertension in cases of
      spontaneous ICH. The present study was a post hoc analysis of the SAMURAI-ICH
      study. We examined relationships between time from onset, imaging, and initiation
      of treatment to target SBP achievement and hematoma growth (absolute growth >=6
      mL) in ICH patients. Target SBP achievement was defined as the time at which SBP
      first became < 160 mm Hg. RESULTS: Among 211 patients, hematoma growth was seen
      in 31 patients (14.7%). The time from imaging to target SBP and time from
      treatment to target SBP were significantly shorter in patients without hematoma
      growth than in those with (p = 0.043 and p = 0.032 respectively), whereas no
      significant difference was seen in time from onset to SBP < 160 mm Hg between
      groups (p = 0.177). Patients in the lower quartiles of time from imaging to
      target SBP and time from treatment to target SBP showed lower incidences of
      hematoma growth (p trend = 0.023 and 0.037 respectively). The lowest quartile of
      time from imaging to target SBP (< 38 min) was negatively associated with
      hematoma growth on multivariable logistic regression (OR 0.182; 95% CI 0.038
      0.867; p = 0.032). CONCLUSIONS: Early achievement of target SBP < 160 mm Hg is
      associated with a lower risk of hematoma growth in ICH.

PMID- 30199856
TI  - Impact of Dysphagia Assessment and Management on Risk of Stroke-Associated
      Pneumonia: A Systematic Review.
AB  - BACKGROUND: Patients with dysphagia are at an increased risk of stroke-associated
      pneumonia. There is wide variation in the way patients are screened and assessed
      during the acute phase. The aim of this review was to identify the methods of
      assessment and management in acute stroke that influence the risk of stroke
      associated pneumonia. Studies of stroke patients that reported dysphagia
      screening, assessment or management and occurrence of pneumonia during acute
      phase stroke were screened for inclusion after electronic searches of multiple
      databases from inception to November 2016. The primary outcome was association
      with stroke-associated pneumonia. SUMMARY: Twelve studies of 87,824 patients were
      included. The type of dysphagia screening protocol varied widely across and
      within studies. There was limited information on what comprised a specialist
      swallow assessment and alternative feeding was the only management strategy,
      which was reported for association with stroke-associated pneumonia. Use of a
      formal screening protocol and early dysphagia screening (EDS) and assessment by a
      speech and language pathologist (SLP) were associated with a reduced risk of
      stroke-associated pneumonia. There was marked heterogeneity between the included
      studies, which precluded meta-analysis. Key Messages: There is variation in the
      assessment and management of dysphagia in acute stroke. There is increasing
      evidence that EDS and specialist swallow assessment by an SLP may reduce the odds
      of stroke-associated pneumonia. There is the potential for other factors to
      influence the incidence of stroke-associated pneumonia during the acute phase.

PMID- 30199857
TI  - Growth Hormone Treatment for Short Stature in the USA, Germany and France: 15
      Years of Surveillance in the Genetics and Neuroendocrinology of Short-Stature
      International Study (GeNeSIS).
AB  - BACKGROUND/AIMS: To describe characteristics, auxological outcomes and safety in
      paediatric patients with growth disorders treated with growth hormone (GH), for
      cohorts from the USA, Germany and France enrolled in GeNeSIS, a post
      authorisation surveillance programme. METHODS: Diagnosis and biochemical
      measurement data were based on reporting from, and GH treatment was initiated at
      the discretion of, treating physicians. Auxological outcomes during the first 4
      years of GH treatment and at near-adult height (NAH) were analysed. Serious and
      treatment-emergent adverse events were described. RESULTS: Children in the USA (n
      = 9,810), Germany (n = 2,682) and France (n = 1,667) received GH (dose varied
      between countries), most commonly for GH deficiency. Across diagnostic groups and
      countries, mean height velocity standard deviation score (SDS) was > 0 and height
      SDS increased from baseline during the first 4 years of treatment, with greatest
      improvements during year 1. Most children achieved NAH within the normal range
      (height SDS >-2). No new or unexpected safety concerns were noted. CONCLUSION: GH
      treatment improved growth indices to a similar extent for patients in all three
      countries despite variations in GH doses. Data from these three countries, which
      together contributed > 60% of patients to GeNeSIS, indicated no new safety
      signals and the benefit-risk profile of GH remains unchanged.

PMID- 30199858
TI  - Assessment of Pyrexia and Associated Sickness Behavior in Patients with Chronic
      Periodontitis.
AB  - BACKGROUND AND OBJECTIVES: The purpose of this study was to assess pyrexia and
      sickness behavior such as anxiety, depression, lethargy, and weight loss in
      subjects with chronic periodontitis, and evaluate inflammatory mediators such as
      erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) in the patients
      with fever. METHODS: This was a cross-sectional study that consisted of 150
      chronic periodontitis and 150 healthy subjects. Sublingual and subgingival
      temperatures were assessed using a digital temperature probe. Associated sickness
      behavior was assessed for all the subjects. Pathological tests, i.e., ESR and CRP
      were done for subjects with fever. RESULTS: Evaluating the presence of fever with
      the severity of periodontal disease, 66.7% of the subjects with fever were in the
      group diagnosed with severe periodontitis, 20.4% had with moderate periodontitis,
      and 5.3% were in the healthy group. Subjects diagnosed with periodontitis
      comprised 66.2% of the subjects with higher (i.e., > 36.3 degrees C) subgingival
      temperatures and healthy subjects made up the remaining 33.8% (p < 0.001). A
      correlation between the sublingual and subgingival temperature with the Pearson
      rho correlation coefficient of 0.227 (p < 0.001) was observed. A statistically
      significant mean value of 37.05 +/- 11.24 of ESR and 1.59 +/- 1.11 mg/L of CRP
      was reported amongst the subjects with fever (p < 0.001). The association of
      sickness behavior with the severity of periodontitis was found to be significant:
      depression 40.006, anxiety 50.857, reported weight loss 76.463, and lethargy
      141.581 (p < 0.001). DISCUSSION AND CONCLUSION: The study demonstrated that there
      is a significant increase in the sublingual temperature amongst patients with
      severe chronic periodontitis. The subgingival temperature has a positive
      correlation with the sublingual temperature. There was a linear trend of an
      association of sickness behavior with the severity of chronic periodontitis. A
      significant increase in the circulating inflammatory mediators, CRP and ESR, were
      noticed in subjects with elevated body temperature.

PMID- 30199859
TI  - Population-Based Screening for Trisomies and Atypical Chromosomal Abnormalities:
      Improving Efficacy using the Combined First Trimester Screening Algorithm as well
      as Individual Risk Parameters.
AB  - AIM: To examine the performance of the combined First Trimester Screening (cFTS)
      algorithm when outliers of 4 risk parameters (maternal age, nuchal translucency
      (NT) thickness, PAPP-A and beta-hCG) were included in the classification of "high
      risk". METHODS: A retrospective analysis of singleton pregnancies undergoing cFTS
      between 2008 and 2011 in Denmark. Abnormal karyotypes were classified as trisomy
      21 (T21), trisomy 13 (T13) and trisomy 18 (T18), sex chromosome aberrations and
      atypical abnormal karyotypes. RESULTS: cFTS was completed in 193,638 pregnancies.
      In 10,205 (5.3%) cases, cytogenetic or molecular analysis was performed pre- or
      postnatally. An abnormal karyotype was seen in 1,122 (11.0%). The algorithm
      identified 87% of T21, 80% of T13, 75% of T18, 79% of sex chromosome aberrations
      and 35% of atypical abnormal karyotypes. Additional classification of a single
      risk parameter outlier (low PAPP-A or free beta-hCG (< 0.2 MoMs), high beta-hCG
      (>=5.0 MoMs), maternal age >=45 years or NT >=3.5 mm) as being at high-risk would
      have improved detection rates to 88, 80, 81, 81 and 37% respectively. The screen
      positive rate increased from 4.4 to 4.8%. DISCUSSION: Addition of outliers of the
      4 parameters used in cFTS algorithm will lead to a statistically significant
      increase in detection rates for chromosomal abnormality.

PMID- 30199860
TI  - Does Maternal Body Mass Index Affect the Quantity of Circulating Fetal Cells
      Available to Use for Cell-Based Noninvasive Prenatal Test in High-Risk
      Pregnancies?
AB  - We present the first study that investigates the effect of maternal body mass
      index (BMI) on the quantity of circulating fetal cells available to use in cell
      based noninvasive prenatal test (cbNIPT). cbNIPT has been proposed as a superior
      alternative to noninvasive prenatal test from cell-free fetal DNA. Kolvraa et al.
      [Prenat Diagn. 2016 Dec; 36(12): 1127-34] established that cbNIPT can be
      performed on as few as one fetal cell, and Vestergaard et al. [Prenat Diagn. 2017
      Nov; 37(11): 1120-4] demonstrated that these fetal trophoblast cells could be
      used successfully in cbNIPT to detect chromosomal and sub-chromosomal
      abnormalities. This study on 91 pregnant women with high-risk pregnancies
      suggests that cbNIPT should not be hampered by an increased BMI because every
      pregnancy, irrespective of the BMI, has rendered fetal cells for downstream
      genetic analysis. The mean number of fetal cells per sample was 12.6, with a
      range of 1-43 cells in one sample. ANOVA showed that increasing maternal BMI
      tends to decrease the number of fetal cells, but not significantly.

PMID- 30199862
TI  - Focus/Summary.

PMID- 30199863
TI  - Changing Paradigms in Acute Kidney Injury: From Mechanisms to Management:
      Proceedings of the 8th Annual UAB-UCSD O'Brien Center Symposium.

PMID- 30199861
TI  - Tretinoin Loaded Nanoemulsion for Acne Vulgaris: Fabrication, Physicochemical and
      Clinical Efficacy Assessments.
AB  - BACKGROUND AND AIM: Acne vulgaris is a common inflammatory skin condition which
      is treated using Tretinoin (TRE), a widely used retinoid. Nano emulations (NEs)
      are colloidal nano-sized particles that enhance the therapeutic efficacy of TRE
      and minimize adverse effects. This study is aimed at developing a TRE-loaded NE
      (NE-TRE) and at assessing the therapeutic effects of the formulation in acne
      vulgaris lesions, compared to conventional 0.05% TRE emulsion. METHOD: The high
      energy emulsification method was used to make NE-TRE. After obtaining stable NE,
      particle characterization and physicochemical properties were evaluated under
      accelerated conditions. Conducting a clinical study, we compared the therapeutic
      effects of NE-TRE and 0.05% TRE emulsion by comparing the number of acne lesions
      and porphyrin production in both sides of the face. RESULTS AND CONCLUSION: We
      successfully developed stable nanoparticles. It was a stable oil-in-water
      emulsion with particle size of about 150 nm, and containing circular and
      separated particles. In a pilot clinical study, the number of acne lesions as
      well as the size and intensity of porphyrin production significantly reduced
      after topical application of NE-TRE. This formula shows proper efficiency and
      good loading capacity of TRE in the drug delivery system.

PMID- 30199864
TI  - Prevalence and Associated Factors of Sarcopenia and Frailty in Parkinson's
      Disease: A Cross-Sectional Study.
AB  - BACKGROUND: Sarcopenia and frailty are found in up to one-third of the general
      elderly population. Both are associated with major adverse health outcomes such
      as nursing home placement, disability, decreased quality of life, and death. Data
      on the frequency of both syndromes in Parkinson's disease (PD), however, are very
      limited. OBJECTIVE: We aimed to screen for sarcopenia and frailty in PD patients
      and to assess potential associations of both geriatric syndromes with demographic
      and clinical parameters as well as quality of life. METHODS: In this
      observational, cross-sectional study, we included 104 PD patients from a tertiary
      center and 330 non-PD controls from a population-based cohort aged > 65 years.
      All groups were screened for sarcopenia using the SARC-F score and for frailty
      using the Clinical Frailty Scale of the Canadian Study of Health and Aging (CSHA
      CFS). Prevalence rates of sarcopenia and frailty were also assessed in 18 PD
      patients from a population-based cohort aged > 65 years. Moreover, PD patients
      from the tertiary center were evaluated for motor and non-motor symptoms, quality
      of life, and dependency. RESULTS: The prevalence of sarcopenia was 55.8% (95% CI:
      46.2-64.9%) in PD patients from the tertiary center and 8.2% (5.7-11.7%; p <
      0.001) in non-PD controls. Frailty was detected in 35.6% (27.0-45.2%) and 5.2%
      (3.2-8.1%; p < 0.001). Prevalence rates for sarcopenia and frailty were 33.3%
      (16.1-56.4%; p = 0.004) and 22.2% (8.5-45.8%; p = 0.017) in the community-based
      PD sample. Both sarcopenia and frailty were significantly associated with longer
      disease duration, higher motor impairment, higher Hoehn and Yahr stages,
      decreased quality of life, higher frequency of falls, a higher non-motor symptom
      burden, institutionalization, and higher care levels in PD patients from a
      tertiary center compared to not affected PD patients (all p < 0.05). CONCLUSIONS:
      Both frailty and sarcopenia are more common in PD patients than in the general
      community and are associated with a more adverse course of the disease. Future
      studies should look into underlying risk factors for the occurrence of sarcopenia
      and frailty in PD patients and into adequate management to prevent and mitigate
      them.

PMID- 30199865
TI  - Hypercoagulation on Thromboelastography Predicts Early Neurological Deterioration
      in Patients with Acute Ischemic Stroke.
AB  - BACKGROUND: Thromboelastography (TEG) provides an integrated measurement of blood
      coagulation function and has been reported to be a useful tool for predicting
      clinical outcomes in patients with cardiovascular diseases. We aimed to
      investigate the application of TEG on admission for predicting early neurological
      deterioration (END) in patients with acute ischemic stroke and its potential
      correlation with the evolution of ischemic lesions. METHODS: Among patients
      consecutively admitted between January 1, 2016, and September 31, 2017, those
      presenting with mild and moderate acute ischemic stroke (National Institutes of
      Health Stroke Scale [NIHSS] score <=14) within 24 h of stroke onset were
      identified and included in this study. TEG was performed on the first day of
      admission. END was defined as an increase of >=1 on subitems of the NIHSS or the
      emergence of new symptoms within 72 h of admission. Demographics, lab test
      results, and TEG values were compared according to whether END occurred. A
      multiple logistic regression model was then developed to investigate the
      predictive power of TEG for END. Receiver operating characteristic (ROC) curves
      were then plotted to evaluate the optimal cutoff values. RESULTS: Of the 246
      eligible patients (mean age 65.3 +/- 12.9 years, 73.6% male), END was identified
      in 72 (29.3%) patients. Patients with END corresponded to a higher proportion of
      females, a more prevalent history of diabetes mellitus (DM), higher baseline
      NIHSS scores, higher serum high-sensitivity C-reactive protein (hsCRP) levels,
      and significantly shorter R on TEG (4.0 +/- 1.0 vs. 4.7 +/- 1.2 min, p < 0.001).
      In further comparisons stratified by R tertiles, significant trends were found
      between shorter R and being female and older and being more likely to exhibit
      diffusion weighted imaging progression on follow-up MRI. After adjusting for
      female sex, baseline NIHSS score, DM, and hsCRP, the lower tertile of R (R <=3.8
      min) was strongly associated with END (OR 3.556, 95% CI 1.165-10.856, p < 0.001).
      ROC analysis demonstrated that R <=3.45 min had the best predictive value for END
      with 87.9% sensitivity and 40.3% specificity. CONCLUSION: Decreased R time on
      admission TEG is associated with END within 3 days in patients with acute
      ischemic stroke.

PMID- 30199866
TI  - Reply to the Comment Entitled "Martin Method for Estimation of Low-Density
      Lipoprotein Cholesterol".

PMID- 30199867
TI  - Effect of Delayed Cord Clamping on Cerebral Oxygenation in Very Preterm Infants.
AB  - BACKGROUND AND OBJECTIVE: The mechanism of reported benefits of delayed cord
      clamping (DCC) are unclear. We aimed to determine whether DCC compared to
      immediate cord clamping (ICC) in very preterm infants improves cerebral
      oxygenation in the first 24 h. STUDY DESIGN: This is a prospective study of a
      subset of infants at < 30 weeks of gestation who were randomised to DCC (>=60 s)
      or ICC (< 10 s) and required an indwelling arterial catheter. Regional cerebral
      oxygenation (rScO2), blood pressure, PI, and peripheral saturation were measured
      and cerebral fractional tissue oxygen extraction (cFTOE) calculated for the
      following 3 time intervals: 3-6, 6-12, and 12-28 h of age. Functional ultrasound
      measures including superior vena cava flow, right ventricular output, ductus
      arteriosus size and shunt and anterior cerebral artery resistive index were
      determined. RESULTS: The mean (+/-SD) gestation and birth weight of the 51 study
      infants were 27 +/- 1 weeks and 1,046 +/- 241 g respectively. Twenty infants
      received DCC and 31 received ICC. Baseline demographics were similar between the
      2 groups. Comparing DCC and ICC infants, there was no difference in rScO2 or
      cFTOE at any time point. Three out of 20 infants did not receive DCC due to
      clinical concerns. A sensitivity analysis revealed that cord clamping >=30 s was
      significantly associated with increased rScO2 and decreased cFTOE at all 3 time
      points after adjusting for gestation. CONCLUSION: Although DCC was not associated
      with changes in cerebral oxygenation overall, sensitivity analysis suggested a
      possible effect of an increased rScO2 and a decreased cFTOE with >=30 s of DCC.

PMID- 30199868
TI  - Effects of Simvastatin on Fetal Cardiac Impairment in the Diaphragmatic
      Experimental Hernia Model.
AB  - BACKGROUND: Statins and sildenafil have been shown to exert beneficial effects in
      cardiac injury. We hypothesized that antenatal maternal administration of
      simvastatin and/or sildenafil might also promote benefits in cardiac remodeling
      of congenital diaphragmatic hernia (CDH). Therefore, we performed micro-CT image
      analysis and histology of the heart after antennal treatment in experimental
      nitrofen-induced CDH. METHODS: At 9.5 days post conception (dpc), pregnant rats
      were exposed to nitrofen. At 16 and 20 dpc fetuses were treated with simvastatin
      and/or sildenafil. At 21 dpc postmortem micro-CT and autopsy were performed.
      RESULTS: All nitrofen-treated fetuses had a lower birth weight compared to
      controls; in the simvastatin-treated group, a significant improvement in CDH was
      noted. Impairment of the lung and liver was also noted in CDH. Compared to
      controls, CDH rats showed lower ventricular mass, with greater left ventricular
      thickness; simvastatin decreased the ventricular mass and improved wall
      thickness. CDH rats exhibited myocardial hypotrophy, severe vascular depression
      in the left ventricle, and intense interstitial edema compared to controls and
      nitrofen-exposed animals without CDH. In CDH, the cardiac morphology appeared
      deformed with left ventricular wall verticalization. Simvastatin improved cardiac
      myocyte appearance and heart morphology. CONCLUSION: The potential to treat CDH
      with antenatal simvastatin may improve the management of this malformation.

PMID- 30199869
TI  - TMEM18: A Novel Prognostic Marker in Acute Myeloid Leukemia.
AB  - BACKGROUND: Certain nuclear envelope proteins are associated with important
      cancer cell characteristics, including migration and proliferation. Abnormal
      expression of and genetic changes in nuclear envelope proteins have been reported
      in acute myeloid leukemia (AML) patients. Transmembrane protein 18 (TMEM18), a
      nuclear envelope protein, is involved in neural stem cell migration and
      tumorigenicity. METHODS: To examine the prognostic significance of TMEM18 in AML
      patients, we analyzed an AML cohort from The Cancer Genome Atlas (TCGA, n = 142).
      RESULTS: Kaplan-Meier survival analysis revealed that TMEM18 overexpression was
      associated with a better AML prognosis with good discrimination (p = 0.019).
      Interestingly, this ability to predict the prognosis was significant in male AML
      patients, but not in female ones. C-index and area-under-the-curve analyses
      further supported this discriminative ability and multivariate analysis confirmed
      its prognostic significance (p = 0.00347). Correlation analysis revealed that
      TMEM18 had a statistically significant positive correlation with nuclear envelop
      protein 133 (NUP133), NUP35, NUP54, NUP62, and NUP88. CONCLUSION: Because the
      current AML prognostic factors do not take mRNA expression into consideration
      unlike other cancers, the development of mRNA-based prognostic factors would be
      beneficial for accurate prediction of the survival of AML patients. Therefore,
      TMEM18 gene is a potential biomarker for AML.

PMID- 30199870
TI  - Perceived Stress and Mild Cognitive Impairment among 32,715 Community-Dwelling
      Older Adults across Six Low- and Middle-Income Countries.
AB  - BACKGROUND: Perceived stress may be a modifiable risk factor for mild cognitive
      impairment (MCI) and ultimately dementia, but studies on this topic from low- and
      middle-income countries (LMICs) are lacking. OBJECTIVE: We assessed the
      association between perceived stress and MCI in six LMICs (China, Ghana, India,
      Mexico, Russia, and South Africa) using nationally representative data. METHODS:
      Cross-sectional, community-based data on individuals aged >=50 years from the
      World Health Organization's Study on Global Ageing and Adult Health were
      analyzed. The definition of MCI was based on the National Institute on Ageing
      Alzheimer's Association criteria. A perceived stress score (range 0 [lowest
      stress] to 10 [highest stress]) was computed based on two questions from the
      Perceived Stress Scale. Multivariable logistic regression analysis was conducted
      to assess the as-sociation between perceived stress and MCI. RESULTS: The mean
      (SD) age of the 32,715 participants was 62.1 (15.6) years and 51.7% were females.
      After adjustment for potential confounders including depression, in the overall
      sample, a one-unit increase in the perceived stress score was associated with a
      1.14 (95% CI = 1.11-1.18) times higher odds for MCI. The association was similar
      among those aged 50-64 and >=65 years. Countrywise analysis showed that there was
      a moderate level of between-country heterogeneity in this association (I2 =
      59.4%), with the strongest association observed in Russia (OR = 1.33, 95% CI =
      1.15-1.55). CONCLUSION: If our study results are confirmed in prospective
      studies, addressing perceived stress may have an impact in reducing the risk for
      MCI and subsequent dementia in LMICs.

PMID- 30199871
TI  - Cutaneous Arteriolosclerosis Is Not Specific to Ischemic Hypertensive Leg Ulcers.
AB  - BACKGROUND: The histological characteristic of hypertensive leg ulcers (HLU) is
      the presence of "arteriolosclerosis." The pertinence of performing a skin biopsy
      to diagnose HLU is questionable, as cutaneous arteriolosclerosis may be related
      to patient comorbidities. The objective here was to evaluate the frequency of
      arteriolosclerosis in skin leg biopsies performed in patients without ulcer and
      in control patients with HLU. METHODS: We performed a retrospective study between
      January 2013 and July 2014. Patients were included if they had undergone a deep
      skin biopsy on the lower limbs, in the absence of any leg ulcer. Controls were
      patients with typical HLU. RESULTS: Fifty-eight patients and 6 controls were
      included. Hypertension was present in 25 patients (43%). Arteriolosclerosis,
      defined as fibrous endarteritis, was present in 35 out of 58 patients (60%) and
      in all of the controls. No hyalinosis or hyperplastic proliferative
      arteriolosclerosis was observed in the patients or controls. Only age was an
      independent factor associated with the presence of cutaneous arteriolosclerosis
      (p &x#3c; 0.0001). CONCLUSION: Cutaneous arteriolosclerosis is significantly and
      independently associated with age. Thus, skin biopsy seems not to be necessary
      for the diagnosis of HLU but only for a differential diagnosis.

PMID- 30199872
TI  - Local Anaesthetic (Medical) Thoracoscopy Services in the UK.
AB  - BACKGROUND: Local anaesthetic thoracoscopy (LAT) is an important procedure in the
      management pathway of patients with pleural effusions, particularly those with
      suspected malignancy. The last survey evaluating the use and development of LAT
      services in the UK was conducted over a decade ago. OBJECTIVES: We performed a
      survey of LAT practices in the UK to explore procedural preferences and
      variations in practice. METHODS: The online survey was cascaded via regional
      pleural specialists to sites performing LAT. One response per site was accepted.
      RESULTS: Thirty-seven responses were received from England, Scotland and Wales.
      Most centres have regular access to a dedicated list and a designated area to
      perform LAT. 97% of the centres have at least 2 trained thoracoscopists. Some
      variation in practice is seen with patient preparation pre-procedure and
      medication use. Other procedures, such as insertion of indwelling pleural
      catheters and adhesiolysis, are not uncommon to be undertaken at the time of LAT.
      CONCLUSIONS: Overall, the results are comparable, excepting some minor variations
      in patient preparation pre-procedure. We hope that this survey functions as an
      information resource for centres developing a LAT service or for those
      considering expansion.

PMID- 30199873
TI  - Optimization of Canine Placenta Decellularization: An Alternative Source of
      Biological Scaffolds for Regenerative Medicine.
AB  - Due to the scarcity of tissues and organs for transplantation, the demand for
      bioengineered tissues is increasing with the advancement of technologies and new
      treatments in human and animal regenerative medicine. Thus, decellularized
      placental extracellular matrix (ECM) has emerged as a new tool for the production
      of biological scaffolds for subsequent recellularization and implantation for
      recovery of injured areas or even for replacement of organ and tissue fractions.
      To be classified as an ideal biological scaffold, the ECM must be acellular and
      preserve its proteins and physical features to be useful for cellular adhesion.
      In this context, we developed a process of decellularization of canine placentas
      with 35 and 40 days of gestation using dodecyl sulfate sodium under immersion and
      agitation in sterile conditions. Before use of this scaffold in recellularization
      processes, the decellularization efficiency needs to be confirmed by the absence
      of cellular content and an irrelevant amount of reminiscent DNA. Both vasculature
      architecture and ECM proteins, such as collagen types I, III, and IV, laminin,
      and fibronectin, were preserved with our method. In this way, we established a
      new biological scaffold model that could be used for recellularization in
      regenerative medicine of tissues.

PMID- 30199875
TI  - Massive Fetomaternal Hemorrhage Remote from Term: Favorable Outcome after Fetal
      Resuscitation and Conservative Management.
AB  - Fetomaternal hemorrhage (FMH) is a rare condition that requires early diagnosis
      and appropriate treatment due to its potentially severe consequences. We report a
      case of massive FMH presenting as decreased fetal movement, fetal hydrops, and
      intracranial hemorrhage at 24 weeks. Treatment considerations were made and
      amniocentesis, fetal blood sampling, and fetal blood transfusion via
      cordocentesis were performed. Recurrent FMH required subsequent fetal transfusion
      2 days later. Surveillance was continued twice weekly until the patient delivered
      a viable infant at 38 weeks after spontaneous labor. Recurrent FMH was
      unpredictable due to its unclear etiology and absence of precipitating events,
      however close surveillance proved effective.

PMID- 30199874
TI  - Novel Facial Cream Containing Carnosine Inhibits Formation of Advanced Glycation
      End-Products in Human Skin.
AB  - BACKGROUND: Accumulation of advanced glycation end-products (AGEs) in skin has
      been associated with skin aging. Inhibition of glycation of proteins of
      extracellular matrix may help skin texture and appearance. The objective of the
      study was to demonstrate the antiglycation activity of topically applied
      carnosine and novel facial cream (FC) containing carnosine in human skin explants
      ex vivo. METHODS: Glycation was induced in human skin explants by methylglyoxal
      (MG) in culture media. FC containing carnosine (FC-CARN) or carnosine in aqueous
      solution (AQ-CARN) was applied topically on skin explants. Levels of AGEs
      carboxymethyl-lysine (CML) and pentosidine were determined in the epidermis and
      dermis of skin sections and were used to calculate antiglycation activity.
      RESULTS: Exposure to MG led to increases in CML and pentosidine in skin explants.
      Antiglycation effect for AQ-CARN was CML: -64 and -41%, pentosidine: -48 and 42%
      in epidermis and reticular dermis respectively. Antiglycation effect for FC-CARN
      was CML: -150 and -122%, pentosidine: -108 and -136%, in epidermis and reticular
      dermis respectively. CONCLUSION: Topically applied carnosine protects against the
      glycation induced by MG. Novel FC-CARN significantly reduced levels of AGEs in
      both epidermis and reticular dermis in human skin explants.

PMID- 30199876
TI  - Patterns and Outcomes of the Top of the Basilar Artery Syndrome: The Role of the
      Posterior Communicating Artery.
AB  - BACKGROUND: Clinical syndromes secondary to infarcts in the distal basilar artery
      (BA) area have been described as "top of the basilar" (TOB) syndrome. However, in
      the era of advanced imaging technology, it has been realized that the clinical
      and imaging features are quite diverse in patients with distal BA occlusion. The
      aim of the present study was to investigate the patterns and clinical outcomes of
      TOB assessed with modern images and categorize TOBs accordingly. Additionally, we
      examined the possible influence of the posterior communicating artery (PcoA) on
      the patterns of TOB. METHODS: Patients with distal BA occlusion on magnetic
      resonance angiography were categorized as TOB-A, and those with multiple lesions
      in the distal BA territory on diffusion-weighted magnetic resonance imaging as
      TOB-L. Patients with angiographically and lesion distribution-defined TOB were
      classified as having TOB-A&L; those with angiographically defined TOB as having
      TOB-A without TOB-L; and those with lesion distribution-defined TOB as having TOB
      L without TOB-A. The PcoA was categorized as "textbook-type" (good P1) and "fetal
      type" (absent P1). Factors associated with unfavorable short-term outcomes
      (modified Rankin Scale 5-6 at discharge), and 1-year and long-term mortalities,
      were assessed. RESULTS: Of 1,466 patients with ischemic stroke in the posterior
      circulation who were admitted to Asan Medical Center within 24 h of symptom
      onset, 124 (8.5%) had TOB, including 45 with TOB-A&L, 44 with TOB-A, and 35 with
      TOB-L. NIHSS scores (21 [9.5-26] vs. 6 [3-11.5] vs. 6 [3-9]; p < 0.01) and rates
      of motor deficit (75.6 vs. 54.5 vs. 34.4%; p < 0.01), concomitant pontine lesions
      (17.8 vs. 25.0 vs. 2.9%; p < 0.01), PcoA presence (44.4 vs. 68.2 vs. 25.7%; p <
      0.01), and unfavorable short-term outcomes (62.2 vs. 25.0 vs. 14.3%; p < 0.01)
      differed significantly in the 3 patient groups. Multivariate analysis showed that
      textbook-type PcoA was independently associated with a lower frequency of
      unfavorable short-term outcomes (OR 0.15, 95% CI 0.03-0.70). Reperfusion therapy
      (hazard ratio [HR] 0.25, 95% CI 0.07-0.89) and the presence of textbook-type PcoA
      (HR 0.20, 95% CI 0.05-0.90) were associated with a lower 1-year mortality rate
      after stroke. CONCLUSION: Patterns and clinical outcomes of TOB vary and are
      affected by the hemodynamic status of the arterial system, such as BA
      recanalization and the presence of textbook-type PcoA.

PMID- 30199878
TI  - Carotid-Jugular Fistula Model to Study Systemic Effects and Fistula-Related
      Microcirculatory Changes.
AB  - BACKGROUND: Arteriovenous fistulae impair the distal circulation, but their
      effects at the microcirculatory level are not well understood. This study
      presents the carotid-jugular fistula (CJF) as a model to evaluate fistula-related
      microcirculatory and systemic changes. MATERIALS AND METHODS: Female Wistar rats
      were anesthetized and divided into a fistula group (FG, n = 10) and a sham group
      (SG, n = 6). End-to-end anastomosis was performed between the right carotid
      artery and the jugular vein in the FG. The hemodynamic status was followed for 6
      weeks. On the sixth postoperative week, liver and kidney microcirculation was
      measured using laser Doppler; then microcirculatory changes were assessed after
      occlusion of the carotid artery. At the end of the experiment, histological
      samples were taken and the weights of the organs were measured. RESULTS: The
      heart rate and systolic blood pressure decreased significantly due to the CJF.
      Laser Doppler showed a reduction in liver blood flow units (BFU) in the FG in
      comparison with the SG (p = 0.01), and they increased (p < 0.01) after occlusion
      of the fistula. Kidney BFU showed slight changes only. The comparative
      morphological study revealed significant increases in heart weight (p < 0.001)
      and left ventricular hypertrophy (p = 0.008) in the FG. CONCLUSION: Beside
      hemodynamic and morphologic changes, a CJF causes a deterioration in the
      microcirculation of the liver rather than of the kidney, but occlusion of the CJF
      immediately reverses these changes.

PMID- 30199877
TI  - Cystic Appearance on Imaging Methods (Bosniak III-IV) in Histologically Confirmed
      Papillary Renal Cell Carcinoma is Mainly Characteristic of Papillary Renal Cell
      Carcinoma Type 1 and Might Predict a Relatively Indolent Behavior of Papillary
      Renal Cell Carcinoma.
AB  - AIM: The aim of this study was to determine the proportion of cystic tumors
      according to preoperative CT (Bosniak III, IV) among surgically treated patients
      with histologically confirmed papillary renal cell carcinoma (pRCC) and to assess
      progression rates among patients with and without cystic appearance on imaging.
      METHODS: A total of 138 patients with pRCC histology surgically treated in the
      period of January 2007-March 2017 were included. Clinical and radiological
      characteristics, type of surgery, histopathology results, and follow-up data were
      recorded and statistically evaluated. RESULTS: Forty-one cases (29.7%) of cystic
      lesions (10* BIIF, 14* BIII, 17* BIV) were detected by CT. Patients with pRCC1
      significantly more frequently presented with cystic appearance on CT (33/78;
      42.3%) in comparison to other papillary types (8/60; 13.3%; p = 0.0002). During a
      median follow-up time of 49.4 months, only 2 patients with cystic lesions
      progressed after surgery. CONCLUSIONS: Cystic appearance on imaging methods is
      mainly a characteristic of pRCC1 (42.3%). Cystic morphology on imaging might
      predict a relatively indolent behavior of all pRCC types. Preoperative scoring
      systems including tumor growth patterns (cystic vs. solid) are needed for further
      classification.

PMID- 30199880
TI  - Focus/Summary.

PMID- 30199879
TI  - Inclusion Cysts after Fetal Spina Bifida Repair: A Third Hit?
AB  - INTRODUCTION: Fetal spina bifida repair (fSBR) has proven effective in the
      reversibility of hindbrain herniation, lower rate of shunt-dependent
      hydrocephalus, and independent ambulation. Besides distinct advantages, there are
      also concerns related to fSBR. One of these is the postnatal occurrence of
      inclusion cysts (IC). METHODS: In a prospective study, 48 children who underwent
      fSBR were followed up. Postnatal assessment included clinical examination,
      cystometry, and spinal MRI. Indication for IC resection was the evidence of a
      spinal mass on MRI in the presence of deteriorating motor or bladder function,
      pain, or considerable growth of the IC. RESULTS: Fourteen children (30%)
      developed IC, all within the first 2 years of life. Six children underwent IC
      resection; 4 children due to deteriorating function, 2 children due to doubling
      of the mass on MRI within 1 year. Following IC resection, 4/6 children (67%)
      demonstrated altered motor function and 6 children (100%) were diagnosed with
      neurogenic bladder dysfunction. CONCLUSIONS: Systematic follow-up of patients
      with a history of fSBR revealed a high incidence of IC. Whether these are of
      dysembryogenic or iatrogenic origin, remains unclear. Since both IC per se and IC
      resection may lead to loss of neurologic function, IC can be considered a "third
      hit."

PMID- 30199881
TI  - Recall and Retention of Consent Procedure Contents and Decisions: Results of a
      Randomized Controlled Trial.
AB  - BACKGROUND: Residual tissue samples, i.e., samples excised for diagnosis or
      during treatment, are commonly used for medical research. In the Netherlands,
      they can be used provided the patient did not opt out of this use. Previous
      research has shown that recall of the informed consent procedure for tissue use
      is poor. Here, we investigate recall of three consent procedures: informed
      consent, opt-out, and opt-out plus (an opt-out procedure with an information
      procedure similar to that of informed consent). METHODS: Patients (n = 1,319)
      with a variety of diseases were randomized into three trial arms: informed
      consent, opt-out plus, and opt-out. Questionnaires were administered 6 weeks and
      6 months after randomization. RESULTS: Six hundred and seventy-three and 553
      patients returned the 6-week and 6-month questionnaire, respectively. In the
      informed consent arm, recall of having received a brochure (55.3%) or oral
      information (69.4%) was similar to that in the opt-out plus arm (48.5 and 71.6%,
      respectively), at the 6-week assessment. Significantly more respondents in the
      informed consent and the opt-out plus arms versus the opt-out arm recalled that
      they had been informed about being able to control tissue use and which consent
      procedure they had experienced (6-week questionnaire range 53.2-75.8 vs. 13.9
      16.1%; 6-month questionnaire range 43.5-84.2 vs. 3.2-35.4%). There were no
      significant differences between the informed consent and opt-out plus arms in
      this regard. CONCLUSIONS: Recall of the consent procedure was similar in opt-out
      plus and informed consent procedures. Overall, recall was moderate, indicating
      that there is room for improvement in the quality of information provision.

PMID- 30199882
TI  - A Review of Diagnostic Impact of Amyloid Positron Emission Tomography Imaging in
      Clinical Practice.
AB  - BACKGROUND: Molecular imaging of brain amyloid for the diagnosis of Alzheimer's
      disease (AD) using positron emission tomography (PET) has been approved for use
      in clinical practice by the Food and Drug Administration (FDA) since 2012.
      However, the clinical utility and diagnostic impact of amyloid PET imaging remain
      controversial. We conducted a review of the recent studies investigating clinical
      utility of amyloid PET imaging with focus on changes in diagnosis, diagnostic
      confidence, and patient management. SUMMARY: A total of 16 studies were included
      in the final analysis. Overall rate of changes in diagnosis after amyloid PET
      ranged from 9 to 68% (pooled estimate of 31%, 95% CI 23-39%). All studies
      reported overall increase in diagnostic confidence or diagnostic certainty after
      amyloid PET. Changes in patient management ranged from 37 to 87%; the most common
      type of change in management reported was either the initiation or
      discontinuation of planned AD medications. Key Messages: Amyloid PET imaging led
      to moderate to significant changes in diagnosis, diagnostic confidence, and
      subsequent patient management. It may be most useful in patients with high level
      of diagnostic uncertainty even after the completing the standard workup.

PMID- 30199884
TI  - Polymorphous Light Eruption: Phototherapy-Based Desensitization Versus
      Intramuscular Steroids - Who Is Right, Who Is Wrong?

PMID- 30199883
TI  - Late-Life Depression versus Amnestic Mild Cognitive Impairment: Alzheimer's
      Disease Incidence in 4 Years of Follow-Up.
AB  - BACKGROUND/AIM: The aim of the study was to evaluate the prognostic power of late
      life depression (LLD) compared with amnestic mild cognitive impairment (aMCI) for
      the onset of Alzheimer's disease (AD) within 4 years of follow-up. METHODS: We
      estimated the incidence of AD in 60 patients presenting with aMCI, 115 patients
      suffering of LLD treated with antidepressants with good compliance, and 66
      healthy control (HC) patients, followed for 4 years. RESULTS: The risk to develop
      AD, within 4 years, was 68.33% for aMCI and 49.57% for LLD. In AD patients 5.60%
      deteriorated without depression, and 72.20% deteriorated with depression after 4
      years of follow-up (p < 0.0001). No HC patients deteriorated to AD or any other
      dementia type. CONCLUSION: In our results, aMCI was the first predictive
      condition that increased the risk to develop AD. Depression is a potentially
      preventable medical condition across the lifespan and may be a modifiable risk
      factor.

PMID- 30199885
TI  - Aloe-Emodin Induces Endoplasmic Reticulum Stress-Dependent Apoptosis in
      Colorectal Cancer Cells.
AB  - BACKGROUND Recently, colorectal cancer has become a more common type of tumor in
      the world. Research has reported that several kinds of single compounds of
      Chinese herbs have shown anti-tumor activity in colorectal cancer. Aloe-emodin
      (AE), a natural compound extract from Aloe Vera, has been discovered to suppress
      cell proliferation and accelerate apoptosis in a variety of tumor cells. Whether
      AE exerts an effect on colorectal cancer cells has not yet been investigated.
      MATERIAL AND METHODS In this study, we examined the impact of AE on SW620 and
      HT29 colorectal cancer cell lines. After treatment with various concentrations of
      AE (10, 20, and 40 MUM), cell proliferation, cell apoptosis, reactive oxygen
      species (ROS) generation, cytosolic calcium level, and related gene expression
      were analyzed. RESULTS Our results indicated that AE suppressed cell viability
      and induced cell apoptosis in SW620 and HT29 cell lines. Furthermore, both cell
      lines when exposed to AE generated ROS, which induces endoplasmic reticulum (ER)
      stress. We then detected the expression of ER stress-related proteins and
      cytosolic calcium levels. We found that cells exposure to AE had upregulation of
      unfolded protein response (UPR) proteins like glucose-related protein 78 (GRP78),
      phosphorylated protein kinase R (PKR)-like ER kinase (p-PERK), phosphorylated
      eukaryotic initiation factor-2alpha (p-eIF2alpha), and transcription factor C/EBP
      homologous protein (CHOP). Meanwhile, we detected an increased cytosolic calcium
      content followed by the upregulation of the calpain-1, calpain-2 and caspase-12.
      CHOP and caspase-12 are important regulatory factors leading to cell apoptosis.
      CONCLUSIONS AE might serve as a candidate in the treatment of colorectal cancer
      through inducing ER stress-dependent apoptosis.

PMID- 30199886
TI  - Decompression sickness, fatness and active hydrophobic spots.
AB  - Since decompression sickness (DCS) in humans was first described, mankind has
      embarked on an odyssey to prevent it. The demonstration that decompression
      releases bubbles, which mainly contain inert gas (nitrogen, helium), into the
      circulation and that the slower the decompression rate the lesser the incidence
      of DCS, resulted in 1908 in the publication of the first, reasonably safe diving
      tables. Besides the development of proper diving tables, the selection of divers
      is also of importance. A relationship between body composition and DCS was
      observed in dogs as long ago as the nineteenth century, an observation supported
      early in the twentieth century: "Really fat men should never be allowed to work
      in compressed air, and plump men should be excluded from high pressure
      caissons...or in diving to more than about 10 fathoms, and at this depth the time
      of their exposure should be curtailed. If deep diving is to be undertaken....
      skinny men should be selected." Alas, nothing is that simple! From my own
      experience it was not always the fat diver who ended up in the treatment chamber
      with DCS. Therefore, other factors must be at play; gender, age, physical
      fitness, and the existence of a persistent foramen ovale (PFO) have all been
      studied as possible factors for the development of vascular gas bubbles and,
      therefore, for DCS. However, none of these factors, alone or in combination,
      explain why there are intra-individual or intra-cohort differences in bubble
      grades (BG). In other words, why does a dive I did today led to a high BG but the
      same dive next week lead to a low one? Or, why is there such a difference in BG
      amongst divers of more or less the same age, gender, body composition and
      physical fitness? In a letter in this issue, a novel hypothesis is postulated
      that may fill in these gaps; active hydrophobic spots (AHS). These AHS can be
      found at the luminal side of capillary, venous and arterial walls and have an
      oligolamellar lining. In an in vitro experiment, nanobubbles developed on AHS
      after a 'dive' to 1,000 kPa (90 msw). It appears that AHS consist of
      dipalmitoylphosphatidylcholine (DPPC), which is the main component of surfactant.
      It is proposed that DPPC may leak from the alveoli into the alveolar capillary
      and be transported to veins and arteries where it precipitates and forms AHS.
      Based on these ideas, it is hypothesized that AHS generate nanobubbles that can
      grow into microbubbles. When these microbubbles detach from the AHS they might
      also take along pieces of the AHS membrane making the AHS smaller or even
      disappear. This phenomenon could explain some of the earlier findings regarding
      the formation of microbubbles in divers. The fact that the presence of
      microbubbles differs between younger and older divers, after repetitive dives,
      and between experienced divers and novice divers can be explained by this model,
      and AHS may be the missing link we are looking for in our quest to understand and
      treat DCS. However, some reservations must be made. Firstly, these observations
      are derived from in vitro and animal experiments and whether or not they reflect
      a similar process in man remains unclear. Secondly, it appears that female divers
      have lower bubble grades after similar dives compared to male divers, suggesting
      lower decompression stress. If AHS is the main generator for microbubbles, there
      should be a difference in the presence of AHS between men and women. We do not
      know from these animal experiments whether there is a gender difference, neither
      does a literature search in PubMed provide us with an answer. Thirdly, as said
      before, DPPC is the main component of surfactant. All alveolar surfactant
      phospholipids, such as DPPC, are secreted to the alveolar space via exocystosis
      of the lamellar bodies (LB) from alveolar type II (ATII) cells. To form a
      functional air-blood barrier, alveolar type I and ATII cells are connected to
      each other by tight junctions. These tight junctions constitute the seal of the
      intercellular cleft and in that way form a true barrier between the alveolus and
      the capillary. Only small molecules like oxygen, carbon dioxide, etc. can
      penetrate through this barrier by themselves due to passive diffusion. All other
      (macro)molecules, including DPPC, need intermediate processes such as ion
      transport proteins, channels, metabolic pumps, etc. to gain access to the
      pulmonary capillary lumen. To my knowledge, no such mechanisms for DPPC or LB are
      known. A theoretical explanation might be the fact that the production of DPPC
      and the exocystosis of DPPC-containing LBs into the alveolar space can be
      stimulated by stretch. Stretch of the alveoli can switch on Ca2+ entry by either
      mechanosensitive channels, store-operated channels or second messenger-operated
      channels, which induces LB exocystosis. Furthermore, an ATP-release mechanism
      might also be responsible for the pulmonary alveolar mechanotransduction of LB.
      During diving, transpulmonary pressure changes occur which might induce
      additional alveolar stretch and thus, theoretically, an extra release of LB.
      However, whether or not such exocystosis of LB is vascularly orientated remains
      unclear. Besides which, the leakage of DPPC from the alveolus to the pulmonary
      capillary might also be as simple as a malfunction of the tight junction due to
      epithelial membrane damage as a result of diving. Finally, it is also possible
      that DPPC is produced in other non-ATII cells in our body of which we are
      currently unaware. To conclude, this is an interesting hypothesis regarding the
      origin of microbubbles. Whether or not DPPC and LB are the main reason for
      individual sensitivity to DCS remains unclear. Further research will hopefully
      identify if DPPC and LB are indeed the missing link or just another branch on the
      big tree of the genesis of decompression sickness.

PMID- 30199887
TI  - Reliability of venous gas embolism detection in the subclavian area for
      decompression stress assessment following scuba diving.
AB  - INTRODUCTION: Ultrasonic detection of venous gas emboli (VGE) in the precordial
      (PRE) region is commonly used in evaluation of decompression stress. While
      subclavian (SC) VGE detection can also be used to augment and improve the
      evaluation, no study has rigorously compared VGE grades from both sites as
      decompression stress indicators. METHODS: This retrospective study examined 1,016
      man-dives breathing air extracted from the Defence Research and Development
      Canada dataset. Data for each man-dive included dive parameters (depth, bottom
      time, total ascent time), PRE and SC VGE grades (Kisman-Masurel) and post-dive
      decompression sickness (DCS) status. Correlation between SC and PRE grades was
      analyzed and the association of the probability of DCS (pDCS) with dive
      parameters and high bubble grades (HBG III- to IV) was modelled by logistic
      regression for SC and PRE separately for DCS risk ratio comparisons. RESULTS: PRE
      and SC VGE grades were substantially correlated (R = 0.66) and were not
      statistically different (p = 0.61). For both sites, pDCS increased with
      increasing VGE grade. When adjusted for dive parameters, the DCS risk was
      significantly associated with HBG for both PRE (p = 0.03) and SC (p < 0.001) but
      the DCS risk ratio for SC HBG (RR = 6.0, 95% CI [2.7-12.3]) was significantly
      higher than for PRE HBG (RR = 2.6, 95% CI [1.1-6.0]). CONCLUSIONS: The
      association of bubble grades with DCS occurrence is stronger for SC than PRE when
      exposure severity is taken into account. The usefulness of SC VGE in
      decompression stress evaluation has been underestimated in the past.

PMID- 30199888
TI  - Provisional report on diving-related fatalities in Australian waters in 2012.
AB  - INTRODUCTION: An individual case review of known diving-related deaths that
      occurred in Australia in 2012 was conducted. METHOD: The case studies were
      compiled using statements from witnesses and reports of the police and coroners.
      In each case, the particular circumstances of the accident and details from the
      post-mortem examination, where available, are provided. RESULTS: There were 26
      reported fatalities (four less than the previous year). Only two of the victims
      were female (one snorkeller and one scuba diver). Fourteen deaths occurred while
      snorkelling and/or breath-hold diving, 11 while scuba diving and one diver died
      while using surface supplied breathing apparatus in a commercial pearl diving
      setting. Two breath-hold divers likely drowned as a result of apnoeic hypoxia.
      Cardiac-related issues were thought to have contributed to the deaths of at least
      three and possibly seven snorkellers and four scuba divers. CONCLUSIONS: Pre
      existing medical conditions; poor organisation, planning and supervision;
      equipment-related problems; snorkelling or diving alone or with loose buddy
      oversight and apnoeic hypoxia were features in several deaths in this series.

PMID- 30199889
TI  - Impact of various pressures on fracture resistance and microleakage of amalgam
      and composite restorations.
AB  - BACKGROUND: Pressure changes can influence dental restorations especially among
      divers. The aim of the current study was to evaluate the fracture resistance and
      microleakage of mesio-occluso-distal (MOD) amalgam and composite restorations
      undergoing pressure changes via diving and aviation simulation. METHODS: For the
      fracture resistance test, 60 sound maxillary premolar teeth were randomly
      allocated to two groups. Each group was then divided into three subgroups (n =
      10) for simulating scuba-diving (pressure cycle to 203 kPa, 2 bar), flight (50.6
      kPa, 0.5 bar), and control (atmospheric pressure). The teeth underwent pressure
      cycles for one month and then the fracture resistance test was conducted on them
      using the Instron testing machine. Microleakage scores were afterwards recorded
      by using a 2% methylene blue dye for 24 hours. RESULTS: Composite restorations
      showed significantly higher fracture resistance values compared to the amalgam
      group (P < 0.05). The control group had significantly higher fracture resistance
      values compared to the dive group, whereas there was no significant difference
      between the control group and the flight group (P = 0.083). No significant
      difference in the level of microleakage was observed between restoration
      materials or pressure cycles (P > 0.05). CONCLUSIONS: Composite restorations
      showed better fracture resistance compared to the amalgam group. However, diving
      pressure cycles demonstrated adverse effects on the fracture resistance values of
      both restorative materials.

PMID- 30199891
TI  - Inner ear barotrauma in divers: an evidence-based tool for evaluation and
      treatment.
AB  - OBJECTIVE: To systematically search the literature for studies evaluating the
      typical presentation and testing that is performed for divers with inner ear
      symptoms and then to create a tool for clinicians when evaluating a diver with
      inner ear symptoms. METHODS: Nine databases, including PubMed/MEDLINE were
      systematically searched through 31 January 2018. The PRISMA statement was
      followed. RESULTS: Three-hundred and two manuscripts were screened, 69 were
      downloaded and 21 met criteria to be included in this review. The articles were
      evaluated for symptomatic trends and initial evaluation work-up primarily
      focusing on inner-ear barotrauma (IEBt) and inner ear decompression sickness
      (inner ear DCS). The trends for IEBt were compared to typical inner ear DCS
      presentation based on large study inner ear DCS results consistent with the
      plethora of research available. Finally, the HOOYAH Tool was developed to assist
      the receiving provider to better determine the most likely diagnosis and thus
      initiate appropriate treatment. The HOOYAH Tool is comprised of the following: 1)
      H: hard to clear; 2) O: onset of symptoms; 3) O: otoscopic exam; 4) Y: your dive
      profile; 5) A: additional symptoms and 6) H: hearing. For each of these
      components, the typical presentation is described allowing the provider better to
      discern the correct diagnosis. CONCLUSION: The diagnosis of IEBt remains
      difficult to define short of visualization through surgical exploration. Early
      treatment is defined by conservative management with a subsequent observational
      period to determine symptomatic resolution and need for surgery. However, a
      similar differential diagnosis is inner ear DCS which requires early
      recompression. The HOOYAH tool provides a method for assisting the provider in
      forming a more confident decision regarding the underlying pathology and
      facilitation of the appropriate treatment.

PMID- 30199890
TI  - Meta-analysis on the effect of hyperbaric oxygen as adjunctive therapy in the
      outcome of anastomotic healing of experimental colorectal resections in rats.
AB  - BACKGROUND: Colorectal cancer is the third most common form of cancer and
      colorectal surgery is the treatment of choice in local disease. Anastomotic
      leakage following colorectal surgery is a major complication with a high
      incidence and mortality. Adjuvant hyperbaric oxygen treatment (HBOT) may be
      associated with reduction of anastomotic leakage. A systematic review was
      conducted regarding HBOT as an adjunctive therapy to colorectal surgery. METHODS:
      Systematic review (1900-2017) using PubMed, Cochrane, EMBASE, Web of Science and
      EMCARE. All original published studies on the effect of HBOT as an adjunctive
      therapy for colorectal surgery with the creation of an anastomosis were
      considered. RESULTS: Thirteen small animal trials were included for qualitative
      synthesis. We found no human trials. Eleven trials used bursting pressure whilst
      eight used hydroxyproline levels as a marker for collagen synthesis as primary
      outcome to assess the strength of the anastomosis. A meta-analysis performed for
      normal and ischaemic anastomoses showed that postoperative HBOT improves bursting
      pressure and hydroxyproline levels significantly in both normal (p <= 0.001 and p
      = 0.02) and ischaemic anastomoses (p <= 0.001 and p = 0.04). CONCLUSION:
      Postoperative HBOT has a positive effect on colorectal anastomoses in rats.
      Further research should focus on a larger systematic animal study.

PMID- 30199892
TI  - A recurrent, ischaemic ileocolonic anastomosis ulcer refractory to surgery
      treated with hyperbaric oxygen.
AB  - A 54-year-old male had undergone right hemicolectomy and ileo-colonic anastomosis
      for carcinoma-in-situ found at colonoscopy. Eighteen months later, he presented
      with a lower gastrointestinal bleed from an anastomotic ulcer, treated with
      resection of the anastomotic site and ileo-sigmoid anastomosis. In the ensuing 12
      months, he had three episodes of haematochezia. Colonoscopy revealed a 12 mm
      anastomotic ulcer necessitating a further colonic resection and re-anastomosis.
      Two-years later, he presented with iron deficiency anaemia. He preferred
      expectant management and received ten iron-infusions over the subsequent four
      years. Thereafter, he developed painless haematochezia. Colonoscopy showed a 15
      mm linear ulcer with mild ooze at the anastomosis. Histology was consistent with
      an ischaemic ulcer; there was no evidence of recurrence of carcinoma-in-situ. The
      ulcer remained refractory to endoscopic and medical treatment, as seen at three
      follow-up colonoscopies. Hyperbaric oxygen treatment (HBOT) was offered and he
      received 30 sessions over six weeks. Colonoscopy at HBOT completion revealed
      healing of the ulcer. The patient had no further overt bleeding and serum
      ferritin has continued to rise spontaneously over 12 months follow-up.

PMID- 30199893
TI  - Fatty diet, active hydrophobic spots, and decompression sickness.
AB  - In a study of the effect of a fatty diet on decompression bubbles, based on the
      responses to a questionnaire regarding daily food consumption, the approximate
      fat intake for each diver was calculated, taking into account the maximum
      recommended intake for a person doing his type of work. Following hyperbaric
      exposure, divers were divided into two groups: 'bubblers' (a minimum of the
      second level on the Kisman-Masurel scale) and 'non-bubblers'. Bubblers had higher
      fat consumption than non-bubblers (146 +/- 39% versus 92 +/- 18%). There was only
      a small difference in body mass index between the two groups: 26.3 +/- 3.3 kg.m-2
      for bubblers and 24.9 +/- 1.9 kg.m-2 for non-bubblers. Cholesterol and
      triglycerides in serum were high in the bubblers (211 +/- 39 mg.dl-1 and 230 +/-
      129 mg?dl-1, respectively) compared with the non-bubblers (188 +/- 34 mg?dl-1 and
      153 +/- 111 mg?dl-1, respectively). The authors concluded that a high-fat diet
      significantly increased the severity of decompression stress in hyperbaric air
      exposures. However, their explanation that the increased amount of fat in the
      serum contained more dissolved nitrogen, and that this was the cause of the
      increase in bubble production, was challenged in a subsequent letter.
      Decompression bubbles can expand and develop only from pre-existing gas
      micronuclei. It is known that nanobubbles form spontaneously when a smooth
      hydrophobic surface is submerged in water containing dissolved gas. We have shown
      that these nanobubbles are the gas micronuclei underlying decompression bubbles
      and decompression sickness. It has been suggested that hydrophobic multilayers of
      phospholipids on the luminal aspect of blood vessels, which we have termed active
      hydrophobic spots (AHS), were derived from lung surfactant. The essential
      components of lung surfactant required to construct the surfactant films, namely
      dipalmitoylphosphatidylcholine (DPPC) and surfactant proteins B and C, were found
      in the plasma of man and sheep, while DPPC was also found at the AHS. These
      findings have borne out the assumption that lung surfactants are the source of
      the AHS on the luminal aspect of blood vessels. These AHS seem to be stable, and
      their number and size increase with age as more DPPC settles. Bubbles may evolve
      at these AHS with decompression. The nanobubbles so formed on the surface of
      these lamellar layers of phospholipids in divers will expand into venous bubbles
      on decompression. The main surfactant in the lung is DPPC (40%), with the
      presence of additional components including other phospholipids, glycerides, and
      cholesterol. In the cited study, only serum triglycerides and cholesterol were
      measured, whereas it may well be that other phospholipids and fatty acids were
      carried by proteins in the plasma. We suggest that, as with the different
      elements which compose the layers of surfactant in the lung, some of the
      additional fatty components carried by the blood will attach themselves to the
      AHS, thus contributing further to their enlargement. We hypothesise that divers
      who consume food that is high in fat, and as a result have more fatty components
      in their blood, will develop more and larger AHS, subsequently becoming bubblers
      with a higher risk of decompression illness.

PMID- 30199894
TI  - Fetal Congenital Pulmonary Airway Malformation: The Role of an Objective
      Measurement of Cardiomediastinal Shift.
AB  - OBJECTIVE:  To examine the relationship between cardiomediastinal shift angle
      (CMSA) and adverse perinatal outcomes and hydrops in cases of congenital
      pulmonary airway malformation (CPAM). STUDY DESIGN:  This retrospective study
      evaluated CPAM cases referred to our institution from 2008 to 2015. The primary
      outcome was a composite score for adverse perinatal outcome. CMSA was measured
      for each case and evaluated for its association with the primary outcome. The
      prediction accuracy of CMSA for adverse perinatal outcome was assessed using
      receiver operator characteristic (ROC) curves. RESULTS:  Eighteen (21.2%) of the
      85 cases experienced an adverse perinatal outcome. Increases in CMSA were
      associated with adverse perinatal outcomes and hydrops in bivariate analyses.
      Adjusted analyses found each 10-degree increase in CMSA to be associated with
      increased odds of an adverse perinatal outcome (adjusted odds ratio [aOR] 2.2,
      95% confidence interval [CI]: 1.4-3.3) and hydrops (aOR 3.0, 95% CI: 1.5-6.1).
      CMSA performed well and was comparable to CPAM volume ratio in predicting adverse
      perinatal outcomes (area under the curve 0.81 and 0.84, respectively).
      CONCLUSION:  We describe a novel measurement of mediastinal shift in cases of
      CPAM and its relationship with adverse perinatal outcomes and hydrops. These
      findings may shape the evaluation and management of CPAMs, improve our
      understanding of their prognosis, and influence patient counseling.

PMID- 30199895
TI  - Isolated Congenital Absence of Cranial Nerves: Report of Two Cases.
AB  - Isolated cranial nerve absence is a rare condition that can be diagnosed using
      high-resolution cranial nerve magnetic resonance (MR) imaging. Thorough clinical
      examination with proper knowledge of the course of cranial nerves may help
      diagnose this rare condition. We describe two cases, one each of, isolated
      congenital absence of the third and seventh cranial nerve with their clinical
      presentation. High-resolution T2-weighted MR imaging was done in both patients
      which revealed absence of cisternal segment of the right-sided third nerve and
      cisternal with canalicular segment of the right-sided facial nerve.

PMID- 30199896
TI  - A De Novo Missense Variant in POU3F2 Identified in a Child with Global
      Developmental Delay.
AB  - Many genetic and nongenetic causes for developmental delay in childhood could be
      identified. Often, however, the molecular basis cannot be elucidated. As next
      generation sequencing is becoming more frequently available in a diagnostic
      context, an increasing number of genetic variations are found as causative in
      children with developmental delay.We performed trio exome sequencing in a girl
      with developmental delay and minor dysmorphological features. Using a filter for
      de novo variants, the heterozygous missense variant c.812A>T, p.(Glu217Val) was
      found in the candidate gene POU3F2 in our patient. POU3F2 plays an important role
      in neuronal differentiation and hormonal regulation. To date, it has not been
      associated with monogenic disorders. Studies on Pou3f2 knockout mice highlighted
      the importance of this protein in the development of the brain. Furthermore,
      microdeletions with an overlapping region including only POU3F2 and FBXL4 were
      linked to developmental delay in six unrelated families. Therefore, POU3F2 is a
      strong candidate gene for developmental delay, although functional assays proving
      this assumption still have to be done.

PMID- 30199897
TI  - Peroral antegrade pancreatoscopy for pancreaticolithiasis after endoscopic
      ultrasound-guided recanalization of a complete pancreaticojejunal stenosis.

PMID- 30199898
TI  - Endoscopic gastrojejunostomy - bigger is better.

PMID- 30199899
TI  - Chronic tracheoesophageal fistula successfully treated using Amplatzer septal
      occluder.

PMID- 30199900
TI  - Comparison of cap-assisted endoscopy vs. side-viewing endoscopy for examination
      of the major duodenal papilla: a randomized, controlled, noninferiority crossover
      study.
AB  - BACKGROUND : Use of a side-viewing endoscope is currently mandatory to examine
      the major duodenal papilla; however, previous studies have used cap-assisted
      endoscopy for complete examination of the papilla. The aim of this study was to
      compare cap-assisted endoscopy with side-viewing endoscopy for examination of the
      major duodenal papilla. METHODS : This was a prospective, randomized, blinded,
      controlled, noninferiority crossover study. Patients were randomized to undergo
      either side-viewing endoscopy followed by cap-assisted endoscopy or cap-assisted
      endoscopy followed by side-viewing endoscope. Photographs of the major duodenal
      papilla were digitally edited to mask the cap area before they were evaluated by
      three blinded external examiners. Our primary end point was complete
      visualization of the major duodenal papilla. Secondary end points were the
      ability to examine the mucosal pattern, the overview of the periampullary region,
      overall satisfaction, and time to locate the papilla. RESULTS : 62 patients
      completed the study. Complete visualization of the major duodenal papilla was
      achieved in 60 examinations by side-viewing endoscopy and in 59 by cap-assisted
      endoscopy (97 % vs. 95 %). The difference between the two examinations was 1.6 %
      with a two-sided 95 % confidence interval of -4.0 % to 7.3 %, which did not
      exceed the noninferiority margin of 8 %. Cap-assisted endoscopy achieved better
      scores regarding the examination of mucosal pattern and overall satisfaction,
      whereas side-viewing endoscopy had a better overview score (P < 0.001, P = 0.004,
      and P < 0.001, respectively). There was no relevant difference in the median
      times to locate the major duodenal papilla. CONCLUSION : Cap-assisted endoscopy
      and side-viewing endoscopy had similar success rates for complete visualization
      of the major duodenal papilla. Cap-assisted endoscopy is superior to side-viewing
      endoscopy regarding the mucosal pattern and overall satisfaction. Side-viewing
      endoscopy gives a better overview of the periampullary region.

PMID- 30199901
TI  - Rosehip Oil Promotes Excisional Wound Healing by Accelerating the Phenotypic
      Transition of Macrophages.
AB  - Poor wound healing is a major and global threat to public health. Efforts have
      been made to better understand the underlying mechanisms and develop effective
      remedies, though the advancements that have been made are still limited. As there
      are no effective and generally applicable therapies available for skin injuries
      and fibrosis, it is urgent to develop new drugs and therapies that facilitate
      wound healing and effectively improve scars. In this study, GC-MS analysis was
      performed to identify the chemical composition of rosehip oil. The excisional
      wound healing model and the carrageenan-induced paw edema method were
      respectively applied to evaluate the wound healing activity and anti-inflammatory
      activity of rosehip oil. Hematoxylin and eosin staining was used to assess the
      pathological changes of sections, and Sirius-red staining was performed to
      analyze the ratio of collagen I/III in wound tissues. Immunohistological staining
      for CD68, CCR7 (CD197), CD163, TGF-beta1, and alpha-SMA was applied to determine
      the macrophage phenotypes transition (M1-to-M2) and demonstrate the scar
      improving efficacy of rosehip oil on wound healing. Results showed that rosehip
      oil significantly promoted wound healing and effectively improved scars. This
      efficacy might be exerted by accelerating the macrophage phenotypes transition
      and inhibiting the process of epithelial-mesenchymal transition.

PMID- 30199902
TI  - 2,6-Dimethoxy-1,4-benzoquinone Inhibits 3T3-L1 Adipocyte Differentiation via
      Regulation of AMPK and mTORC1.
AB  - 2,6-Dimethoxy-1,4-benzoquinone is a natural phytochemical present in fermented
      wheat germ. It has been reported to exhibit anti-inflammatory, antitumor, and
      antibacterial activities. However, the anti-adipogenic effects of 2,6-dimethoxy
      1,4-benzoquinone and the mechanisms responsible have not previously been
      elucidated. Such findings may have ramifications for the treatment of obesity.
      2,6-Dimethoxy-1,4-benzoquinone (5 and 7.5 uM) significantly reduced the
      expression of various adipogenic transcription factors, including peroxisome
      proliferator-activated receptor-gamma and CCAAT/enhancer binding protein alpha as
      well as adipocyte protein 2 and fatty acid synthase. 2,6-Dimethoxy-1,4
      benzoquinone upregulated AMP-dependent protein kinase phosphorylation and
      inhibited the mature form of sterol regulatory element-binding protein 1c.
      Notably, 2,6-dimethoxy-1,4-benzoquinone attenuated mammalian target of rapamycin
      complex 1 activity in 3T3-L1 and mouse embryonic fibroblast cells. These findings
      highlight a potential role for 2,6-dimethoxy-1,4-benzoquinone in the suppression
      of adipogenesis. Further studies to determine the anti-obesity effects of 2,6
      dimethoxy-1,4-benzoquinone in animal models appear warranted.

PMID- 30199903
TI  - 7-O-Methylwogonin from Scutellaria baicalensis Disturbs Mitotic Progression by
      Inhibiting Plk1 Activity in Hep3B Cells.
AB  - Polo-like kinase 1, a mitotic Ser/Thr kinase, has emerged as a molecular target
      for the development of anticancer drugs. In this study, we found that polo-like
      kinase 1 activity was inhibited by 7-O-methylwogonin and related flavones,
      including baicalein, dihydrobaicalein, and viscidulin II, isolated from
      Scutellaria baicalensis. Although dihydrobaicalein exhibited the highest polo
      like kinase 1 inhibitory activity among the four compounds, it also inhibited
      other kinases, such as vaccinia-related kinase 2 and polo-like kinase 2.
      Baicalein and viscidulin II also showed low selectivity to polo-like kinase 1
      since they inhibited polo-like kinase 3 and polo-like kinase 2, respectively.
      However, 7-O-methylwogonin exhibited selective polo-like kinase 1 inhibitory
      activity, as evidenced from in vitro kinase assays based on fluorescence
      resonance energy transfer assays and ADP-Glo kinase assays. In addition,
      examination of mitotic morphology and immunostaining using specific antibodies
      for the mitotic markers, p-histone H3 and mitotic protein monoclonal 2, in Hep3B
      cells showed that 7-O-methylwogonin treatment increased mitotic cell populations
      due to inhibition of mitotic progression as a result of polo-like kinase 1
      inhibition. The pattern of 7-O-methylwogonin-induced mitotic arrest was similar
      to that of BI 2536, a specific polo-like kinase 1 inhibitor. Thus, it was
      suggested that 7-O-methylwogonin disturbed mitotic progression by inhibiting polo
      like kinase 1 activity. These data suggest that 7-O-methylwogonin, a polo-like
      kinase 1 inhibitor, may be a useful anticancer agent because of its polo-like
      kinase 1 selectivity and effectiveness.

PMID- 30199904
TI  - Augmentation of Pharmacotherapy by Sleep Deprivation with Sleep Phase Advance in
      Treatment-Resistant Depression.
AB  - INTRODUCTION: The aim was to assess the efficacy of total sleep deprivation (TSD)
      with sleep phase advance (SPA) in treatment-resistant depression (TRD) and
      associated biochemical factors. METHODS: We studied nine males and 12 females,
      aged 49+/-14 years, with treatment-resistant unipolar or bipolar depression,
      receiving antidepressant and mood-stabilizing drugs. The four-day schedule
      included single TSD and three consecutive nights with SPA. Biochemical markers
      were measured on the day before and on 1st, 7th and 14th day after the TSD.
      RESULTS: Ten subjects met criteria for response, defined as a reduction of >=50%
      in the Hamilton Depression Rating Scale, on the 14th day. Concentrations of
      cortisol at baseline were lower in responders, and they decreased during therapy
      in both groups. In responders, there was an increase of interleukin-10 (IL-10)
      and IL-1beta on the 14th day. DISCUSSION: Our preliminary study demonstrated the
      efficacy of pharmacotherapy augmentation by TSD and SPA in half of the patients
      with TRD. The main biochemical factors related to clinical response included
      status of cortisol and increase in IL-10 and IL-1beta levels.

PMID- 30199905
TI  - [What is Known About the Real Length of Postgraduate Medical Education in
      Germany?]
AB  - OBJECTIVE: This study examines the real length of postgraduate medical education
      in Germany. The regulations define minimal time periods in months for each
      discipline. We especially analyze the differences between minimum and real
      length, as well as the percentages of interrupting or dropping out physicians by
      gender. METHODS: Within the KarMed study, annual postal surveys were sent to
      graduates of seven medical faculties in Germany from their last year of
      undergraduate education until after six years of postgraduate training. The
      return rate at baseline was 48 % (n = 1012) and the 5 surveys after baseline
      reached rates of 85 % and more. Descriptive statistics were used for analyses.
      RESULTS: Half of the residents did not finish within the minimum time period.
      This proportion was higher among women (65 %) then men (43 %); among women with
      child/children this proportion reached 91 %. Female residents expecting a
      prolongation estimated an average time period of 19.6 months (SD = 14.7), male
      residents of 11.5 months (SD = 8.6).Female residents named problems in relation
      to children as the most important factor. Half of the reasons given by male
      residents (and 31 % of those given by females) are related to organizational and
      curricular problems of postgraduate education. CONCLUSION: Effective measures are
      needed to reduce the problem of continuation of postgraduate education in the
      course of getting/having children and/or to promote the return to training in the
      hospital. For this, curricular and organizational measures, e. g. rotation plans
      and better possibilities for part-time training, should be offered.

PMID- 30199907
TI  - [Diagnosis and Therapy of Leukemia: a Result of Groundbreaking Research].

PMID- 30199906
TI  - [Control of Respiratory Symptoms During Sleep in Patients with Stable Bronchial
      Asthma].
AB  - INTRODUCTION: Awareness of respiratory symptoms during day- and night-time is
      important for asthma control. Acoustic long-term recording offers a possibility
      to monitor symptoms objectively. In this prospective observational study
      frequency of night-time cough and wheezing was evaluated in patients with stable
      asthma. METHODS: Night-time cough and wheezing were monitored by LEOSound lung
      sound monitor in 40 patients with stable asthma. Patients did not complain of
      respiratory problems during day- and nighttime, asthma control test was 23 points
      on average. FEV1 was 84 +/- 15 %; MEF 50 71 +/- 27 % and Rtot 0,48 +/- 0,18
      kPas/l. The age of the patients was 35 +/- 11 years. All patients had an
      antiobstructive and/or anti-inflammatory medication. The present study focuses on
      description of frequency, severity and characteristics of night-time symptoms
      like cough and wheezing in patients with stable asthma and tries to depict
      differences in patients who present cough or wheezing. RESULTS: Wheezing was
      monitored in 2 of the 40 patients. In the first patient duration of wheezing was
      19 min, in the second 55 min. Lung function in patient 1 showed a moderate
      bronchial obstruction, he was still smoking. Patient 2 was a non-smoker with a
      significant bronchial obstruction (FEV1 49 %; MEF 50 27 % and Rtot 0,52 kPas/l).
      In 26 patients there was no coughing, 14 patients had 4 +/- 3 (2 - 13) cough
      epochs during the night. By dividing the collective in two groups differentiated
      by the presence of cough/ no cough we found no significant differences regarding
      lung function and ACT-scores. Both patients with night-time wheezing presented
      low ACT- Scores (20 and 21 points). CONCLUSIONS: Nocturnal wheezing and cough
      episodes were detectable in 2 respectively 14 patients with stable asthma. Long
      term recording of normal and adventitious breath sounds offers a practical
      opportunity to evaluate night-time cough and wheezing objectively.

PMID- 30199908
TI  - [76-Year Old Male with Progressive Thoracic Pressure Sensation].

PMID- 30199909
TI  - [AML in Adults - An Update on Diagnosis, Risk Classification and Therapy].
AB  - There are several changes in the revised WHO classification for acute leukemia.
      The latest version of the European Leukemia Network (ELN)-risk classification
      defines AML with mutations in RUNX1, ASXL1 or TP53 to fall in the unfavorable
      risk group. Consequently, the somatic molecular genetic testing at the time of
      initial diagnosis should encompass these before mentioned three genes next to the
      already routine testing of NPM1, CEBPA and FLT3-ITD. Several new innovative
      substances have been developed and approved for AML therapy. The multikinase
      inhibitor midostaurin is a new substance in the induction therapy for patients
      with FLT-3 mutated AML. CPX-351 (cytarabin and daunorubicin in liposomatic
      formulation in a defined molar relation) is a new option for therapy associated
      AML and AML with myelodysplastic changes. Enasidenib is a targeting drug for
      relapsed or refractory AML with IDH2 mutation. Gemtuzumab, a CD33 + antibody-drug
      conjugate is approved for CD33 positive cases.

PMID- 30199910
TI  - [Chronic Myelogenous Leukemia].
AB  - The advent of tyrosine kinase inhibitors (TKI) has improved prognosis and outcome
      of patients with chronic myelogenous leukemia (CML) considerably. In comparison
      to imatinib, first line use of second generation inhibitors nilotinib, dasatinib
      and bosutinib lead to faster and deeper molecular remissions accompanied by a
      novel adverse event profile. Essential part of the management of CML patients is
      a consequent use of cytogenetic and molecular follow up with standardized methods
      to regularly assess the remission status. Long lasting remission without
      treatment in an important minority of patients prompted the hope for curability
      of CML. The use of interferon alpha in parallel with or after TKI therapy is
      associated with the induction of an immune response against the leukemic clone
      with further improved remission rate. The cooperative management of CML patients
      permits the early use of novel treatment options in patients at risk.

PMID- 30199911
TI  - [Acute Lymphoblastic Leukemia - Diagnostics, Subgroups and Therapies].
AB  - The acute lymphoblastic leukemia (ALL) is a heterogenous rare malignant disease
      of lymphoblastic precursor cells. The peak of incidence lies in childhood
      (5.3/100 000), but the incidence rises again from the age of 50 onwards, showing
      a second peak at patients > 80 years old (2.3/100 000). The ALL is an acute life
      threatening disease which untreated leads to death within a short time. The
      therapeutic objective is cure. By the characterization of subgroups, their
      targeted therapy and therapy optimization cure rates could be improved (from less
      than 10 % in the eighties) to more than 50 - 70 % (depending on the subgroup). To
      this achievement the approach has contributed with risk adapted therapy
      protocols, with improved supportive therapy and in particular with taking the
      minimal residual disease (the most important prognostic factor) as a basis for
      the therapy decision. Recently, with the new immunotherapies there exist further
      promising options of targeted therapies.

PMID- 30199912
TI  - [Individualized Treatment of Chronic Lymphocytic Leukemia (CLL)].
AB  - Because of the excellent prognosis in early asymptomatic stage of the disease all
      patients outside clinical trial should undergo "watch & wait" independently of
      their individual risk profile. Prognostic markers and scoring systems, as the CLL
      international prognostic index (CLL-IPI), help predicting the individual
      prognosis. In advanced stage disease standard frontline therapy in patients
      without high risk factors is still the combination of chemotherapy and CD20
      antibody. However, particularly elderly patients with unfavorable prognostic
      factors may alternatively be treated with the Btk-inhibitor. Novel targeted
      agents are the treatment of choice in presence of high risk prognostic factors as
      well as in most relapsed situations. They are currently tested in currently
      ongoing trials in frontline.

PMID- 30199913
TI  - [Local Allergic Reaction to Subcutaneous Treatment with Procaine in a Patient
      with Shoulder Pain - a Case Study].
AB  - HISTORY: A 53-year-old man presented at the general practitioner's office with 2
      weeks of existing shoulder pain without radiation. On physical examination, no
      abnormalities were found, except for left-sided tension of the shoulder muscles.
      FINDINGS AND DIAGNOSIS: Because of the expected self-limiting nature of the
      complaints, no further tests were conducted. Based on shoulder pain with local
      muscle tension, the working diagnosis cervicobrachialgia was adopted. THERAPY AND
      COURSE: The pain was treated with local subcutaneous administration of procaine.
      4 days later, the patient presented with distinct patches of urticaria at the
      injection sites, which regressed spontaneously over the course of 2 weeks.
      DISCUSSION: Allergic reactions occuring after treatment with procaine are rare,
      but can be life-threatening if systemic or afflicting vital structures.Patients
      should be informed about the importance of the allergy in relation to medical
      procedures, such as dental treatment, and about cross-reactivity with other
      medication.

PMID- 30199914
TI  - [Sonography of the Joints - Step by Step].
AB  - The availability of modern ultrasound machines with high resolution scanners and
      sensitive Doppler functions facilitates the investigation of joints and tendons
      in different conditions. It should be the first diagnostic step in
      musculoskeletal diseases which is done in a structured sequence according to
      official guidelines.

PMID- 30199915
TI  - [The Changing Appearance of Cardiac Amyloidosis].
AB  - A fast and reliable diagnosis of cardiac amyloidosis requires a significant
      amount of clinical awareness. It is especially important to come to an early
      diagnosis in patients with cardiac AL amyloidosis in order to improve the
      otherwise unfavourable clinical course in these patients. There is a significant
      increase in the number of patients with cardiac amyloidosis of the ATTR wild-type
      variety. These patients are often elderly males presenting with predominantly
      right sided heart failure. We present a diagnostic pathway enabling a structured
      approach to these patients using multimodality cardiac imaging and endomyocardial
      biopsy. Early chemotherapy is the key to improving symptoms in patients with AL
      amyloidosis. In contrast, pharmacologic approaches for treating cardiac ATTR
      amyloidosis need further research and clinical trials.

PMID- 30199916
TI  - Interaction Between Lactate and Uric Acid is Associated With a Higher Prevalence
      of Metabolic Syndrome: A Community-Based Study.
AB  - BACKGROUND: Increased blood lactate or uric acid (UA) levels are associated with
      an increased risk of metabolic syndrome (MS). The aim of this study was to
      investigate the effect of an interactive association between blood lactate and UA
      levels on MS. METHODS: This community-based cross-sectional study included 2584
      Chinese subjects aged >= 18 years. Participants were classified into 3 groups
      based on lactate or UA level tertiles or into 9 groups based on a combination of
      lactate and UA level tertiles. RESULTS: The serum high-sensitivity C-reactive
      protein (hs-CRP) and homeostatic model assessment of insulin resistance (HOMA-IR)
      levels and odds ratios (ORs) for MS increased across the blood lactate or UA
      level tertiles (all P for trend<0.05). Interactions between lactate and UA with
      hs-CRP level, HOMA-IR level, and ORs for MS (P<0.05 for all interactions) were
      also observed. The adjusted ORs for MS in participants in the third tertile of
      lactate and UA levels, in the third tertile of lactate levels and first tertile
      of UA levels, and in the first tertile of lactate levels and third tertile of UA
      levels were 6.02 (95% CI 2.87-12.64, P<0.001), 2.92 (95% CI 1.39-6.10, P=0.005),
      and 2.70 (95% CI 1.23-5.96, P=0.014), respectively, compared with those in the
      first tertiles of both lactate and UA levels. CONCLUSION: The interaction between
      lactate and UA is associated with a higher prevalence of MS in the Chinese
      population.

PMID- 30199917
TI  - Inherited Forms of Primary Hyperaldosteronism: New Genes, New Phenotypes and
      Proposition of A New Classification.
AB  - Primary aldosteronism is a common cause of endocrine hypertension. It results
      from the excess production of aldosterone by the adrenal cortex and is related to
      increased morbidity and mortality. Most cases of PA are sporadic but inherited
      patterns of the disease have been reported in the literature. Four forms of
      familial hyperaldosteronism (FH-I- FH-IV) are currently recognized, and the
      genetic basis has been clarified in recent years. In FH-I patients, aldosterone
      excess is produced by a CYP11B1/CYP11B2 fusion gene and it is suppressed by
      glucocorticoid treatment. FH-II is caused by mutations in the inwardly rectifying
      chloride channel CLCN2. FH-III is caused by mutations in KCNJ5, a gene coding for
      an inward rectifier K+ channel and mutations in the T-type calcium channel
      subunit CACNA1H cause FH-IV. In this review we summarize the knowledge on
      inherited forms of primary aldosteronism, the genetic alterations that cause them
      and the implications it may have for the classification. Based on current
      evidence, we propose the term "familial hyperaldosteronism" to refer only to
      inherited forms of primary aldosteronism with a known genetic basis.

PMID- 30199918
TI  - Sarcopenia - Endocrinological and Neurological Aspects.
AB  - Sarcopenia in geriatric patients is often associated with or even caused by
      changes of the endocrine and nervous system. The multifactorial pathogenesis of
      sarcopenia and additional multimorbidity in geriatric patients makes it difficult
      to study distinct pathogenic pathways leading to sarcopenia. Patients suffering
      from diabetes, Cushing's syndrome, chronic kidney disease, Klinefelter's syndrome
      or motor neuron diseases, such as amyotrophic lateral sclerosis for example are
      known to have impaired muscle property and reduced physical performance. These
      patients are typically younger and suffer from conditions caused by a known
      molecular disease mechanism and a peculiar sarcopenic phenotype. Therefore, these
      sequelae can serve as prototypic disease models to study isolated
      endocrinological and neurodegenerative causes for sarcopenia. This review focuses
      on diseases whose etiopathogenesis of muscle impairment is known. The idea is to
      use these diseases as proof of principles to develop a classification algorithm
      of sarcopenia in the elderly to make a more mechanism-oriented therapy be
      possible.

PMID- 30199919
TI  - Changes in Von Willebrand factor profile predicts clinical outcomes in patients
      on mechanical circulatory support.
AB  - BACKGROUND: The associations between mechanical circulatory support (MCS),
      acquired von Willebrand syndrome (AvWS), and clinical outcome are incompletely
      understood. METHODS: In 128 heart failure patients with pulsatile MCS implants
      (65 total artificial heart or biventricular assist device implants, 63 left
      ventricular assist device [LVAD] implants) and 76 patients with continuous flow
      LVAD implants, we analyzed the von Willebrand factor (vWF) profile before (<=24
      h) and 17.5 (standard deviation: 5.1) days after device implant. We determined
      vWF concentrations, vWF activity, and vWF collagen binding capacity and
      calculated ratios of vWF activity/binding capacity with vWF concentration. The
      relation of the vWF profile with clinical outcomes such as stroke,
      gastrointestinal bleeding, and survival was also evaluated. Events were assessed
      up to 1 year of device implant. RESULTS: All entities of vWF were already
      significantly elevated preoperatively and remained high after MCS implantation.
      The ratios of vWF activity/concentration (vWF:RCo/Ag) and collagen binding
      capacity/concentration (vWF:CBA/Ag) were significantly reduced preoperatively and
      remained low postoperatively, indicating AvWS. The preoperative alterations in
      the vWF profile were already present in patients without intra-aortic balloon
      pump and/or extracorporeal circulatory membrane oxygenation implants. The vWF
      profile was unrelated to postoperative stroke. However, a higher postoperative
      ratio of vWF:CBA/Ag was independently associated with increased gastrointestinal
      bleeding. In addition, a postoperative increase in vWF concentrations and
      activity were independent predictors of increased 1-year mortality. CONCLUSIONS:
      Our data indicate that AvWS is present in heart failure patients before device
      implantation, and is independently associated with clinical outcomes, especially
      with 1-year mortality.

PMID- 30199920
TI  - Non-anastomotic failure of woven Dacron tube grafts in the thoracic aorta in
      young adults.
AB  - BACKGROUND: Dacron tube grafts have been used in the surgical management of
      cardiovascular disease since the 1970s. Complications at the site of the
      anastomosis have been well described. Non-anastomotic failure is far less common.
      We present a series of four patients who presented with complications of non
      anastomotic failure of woven Dacron tube grafts. METHODS: A retrospective chart
      review of four patients who presented to our institution between March 2014 and
      March 2017 with clinical complications of a Dacron tube graft was conducted.
      RESULTS: All four patients underwent a staged surgical repair for an interrupted
      aortic arch between the years of 1988 and 2001. All four patients underwent
      revision of their original interposition graft (Gore-Tex, W.L. Gore & Associates,
      Flagstaff, AZ) with implantation of a Hemashield woven Dacron tube graft (Maquet,
      Rastatt, Germany). From 13 to 22 years postimplant of the Dacron tube graft, all
      patients presented with symptoms or clinical evidence of primary graft failure.
      Two patients underwent urgent surgical intervention and did not survive. One
      patient underwent attempted surgical intervention, which was aborted in the
      setting of profuse bleeding, and ultimately had an endovascular rescue of the
      tube graft with a Zenith Alpha endograft (Cook Medical, Bloomington, IN). One
      patient underwent elective endovascular intervention prior to onset of symptoms.
      CONCLUSION: Non-anastomotic failure of woven Dacron tube grafts can occur in the
      thoracic aorta in young adults and may be managed with endovascular techniques.

PMID- 30199921
TI  - Coronary artery bypass for multiple coronary artery aneurysms due to Kawasaki
      disease.

PMID- 30199922
TI  - Rheumatoid nodule on the anterior mitral valve leaflet.
AB  - Symptomatic cardiac rheumatoid nodules are a rare but recognized manifestation of
      rheumatoid arthritis. We describe the surgical management of a rheumatic nodule
      involving the anterior leaflet of the mitral valve.

PMID- 30199923
TI  - Growth performance and post-weaning diarrhoea in piglets fed a diet supplemented
      with probiotic complexes.
AB  - Weaning stress can affect the growth performance and intestinal health of
      piglets. Dietary alternatives to antibiotics, such as dietary probiotics,
      especially those containing multiple microbial species, are a preventive strategy
      for effectively controlling post-weaning diarrhoea. In this study, we
      investigated forty-eight crossbred piglets in three treatment groups for 21 days:
      the control and experimental group supplemented with Enterococcus faecium DSM
      7134, Bacillus subtilis AS1.836 plus Saccharomyces cerevisiae ATCC 28338 (EBS) or
      Lactobacillus paracasei L9 CGMCC No. 9800 (EBL). On day 21, weaned piglets
      supplemented with two kinds of probiotic complexes increased growth performance
      of piglets, reduced post-weaning diarrhoea significantly (P < 0.05). The EBS
      treatment increased acetic acid and propionic acid in the faeces (P < 0.05), and
      the EBL treatment increased faecal acetic acid, propionic acid, butyrate and
      valerate(P < 0.05). Moreover, the faecal microbiota of piglets changed markedly
      in EBL treatment. The addition of EBS and EBL may have similar effects on the
      prevention of diarrhoea by improving the intestinal morphology and regulating the
      microbiota during the weaning period.

PMID- 30199924
TI  - Hepatitis E Virus Methyltransferase Inhibits Type I Interferon Induction by
      Targeting RIG-I.
AB  - The type I interferons (IFNs) play a vital role in activation of innate immunity
      in response to viral infection. Accordingly, viruses have evolved to employ
      various survival strategies to evade innate immune responses induced by type I
      IFNs. For example, HEV encoded papainlike cysteine protease (PCP) has been shown
      to inhibit IFN activation signaling by suppressing K63-linked de-ubiquitination
      of retinoic acid-inducible gene I (RIG-I) and TANK-binding kinase 1 (TBK1), thus
      effectively inhibiting down-stream activation of IFN signaling. In present study,
      we demonstrated that hepatitis E virus (HEV) inhibits poly inosinicpolycytidylic
      acid (poly(I:C))-induced IFN-beta transcriptional induction. Moreover, by using
      reporter assay with individual HEV-encoded gene, we showed that HEV
      methyltransferase (MeT), a non-structural protein, significantly decreases RIG-I
      induced IFN-beta induction and NF-kappaB signaling activities in a dose-dependent
      manner. Taken together, we report here that MeT, along with PCP, is responsible
      for the inhibition of RIG-I-induced activation of type I IFNs, expanding the list
      of HEV-encoded antagonists of the host innate immunity.

PMID- 30199925
TI  - The Irish Journal of Psychological Medicine: looking to the future.

PMID- 30199926
TI  - Eating problems in Irish children and adolescence - EPICA.
AB  - OBJECTIVES: To examine eating concerns in a cohort of Irish adolescents. METHODS:
      Students from a stratified random sample of post primary schools were screened
      using the EAT-26, the EDI-III and a study specific questionnaire. RESULTS: A
      total of 3,031 students (mean age 14.74, range 12-19) enrolled in the study. The
      majority of respondents felt popular (91%), happy (75.2%) and perceived
      themselves to have a good quality of life (86.8%). Despite this, 32% of females
      dieted, 29.4% were dissatisfied with their bodies, and 10.8% scored above 20 on
      the EAT-26. Adolescents always on a diet reported a lower quality of life (QoL)
      X2(16, N=2,961) =144.43, p <.000, perceived themselves to be less popular X2(15,
      N=2,963) =53.26, p <.000 and less academically able X2(16, N=2,297) =43.96,
      p<.000, than those who never dieted. Comparing EPICA values to published norms,
      Irish males had significantly lower EAT scores, females had comparable total EAT
      26 scores but significantly lower levels of dieting and higher levels of bulimic
      features and oral control. Girls in mixed schools had higher rates of body
      dissatisfaction F (1,2855) = 16.61, p <.001 and drive for thinness F (1,2860) =
      11.78, p <.005 than girls attending same sex schools. CONCLUSIONS: Weight and
      body image concerns were high among Irish adolescents, especially females, with
      higher than expected levels of bulimia and oral control scores on the EAT but
      lower scores on the dieting subscale. Females attending mixed sex schools appear
      most at risk of eating pathology.

PMID- 30199927
TI  - Effects of the anticonvulsant topiramate on language abilities in people with
      epilepsy: a cross-sectional study.
AB  - OBJECTIVES: The aim of this study was to investigate the effects of topiramate
      (TPM) on cognitive function, specifically language, in patients with epilepsy,
      and to determine whether a specifically designed neuropsychological test battery
      can show such effects. METHOD: Twenty patients taking TPM, 25 epilepsy controls
      (taking medication other than TPM) and 25 healthy controls were recruited. We
      used a specific neuropsychological battery, including measures of visual and
      verbal memory, attention, fluency and comprehension. Separate one way between
      group ANOVAs were performed for each neuropsychological measure. RESULTS:
      Bonferroni comparisons revealed that the TPM group performed significantly worse
      than epilepsy controls on digits forward (p<0.001), digits backward (p<0.05),
      controlled oral word association (COWA) (p<0.05) and token test (p<0.05). The TPM
      group also needed more multiple choice cues in the Boston naming test (p<0.05).
      CONCLUSIONS: The present study indicates that 15% of the sample tested had
      impaired language abilities and raises interesting questions regarding the nature
      of this effect. Furthermore, we have identified some short neuropsychological
      tasks that can be performed in routine clinical situations that can reliably
      identify patients who have negative linguistic effects of TPM.

PMID- 30199928
TI  - Use of seclusion in a general hospital acute psychiatric unit.
AB  - OBJECTIVE: To examine the frequency of use of seclusion and the factors
      associated with its use in Lakeview Unit, a 29-bedded acute psychiatric unit in
      Naas General Hospital. METHODS: A survey was carried out involving a
      retrospective chart review of all patients secluded over a 12-month period, as
      well as a review of the seclusion register for this period. Secluded and non
      secluded patients were compared for gender, nationality, age, diagnosis, duration
      of admission and admission status by reviewing discharge summaries of all
      patients admitted during the 12-month period. RESULTS: Most (75%) of the secluded
      patients were secluded only once. Half of seclusion events were initiated in the
      first week of admission. Length of time spent in seclusion ranged from 50 minutes
      to 96 hours, with a mean duration of 25 hours 20 minutes. Seclusion was most
      often associated with risk to others and risk to self. Alternatives to seclusion
      considered included verbal de-escalation, medication, special nursing, single
      room accommodation and time out Male and non-Irish patients were more likely to
      be secluded. There was no significant difference between secluded and non
      secluded patients in terms of age. Patients with psychotic disorders tended to be
      secluded more frequently than others, followed by patients with bipolar affective
      disorder and substance use disorders. Longer duration of admission and
      involuntary admission status were strongly associated with seclusion. CONCLUSION:
      Seclusion remains an important part of psychiatric practice on Lakeview Unit, and
      reflects indirect measures of illness severity. In order to reduce the duration
      of seclusion episodes, the development of alternative containment strategies
      needs to be addressed. Seclusion audits should be carried out regularly to ensure
      that best practice is adhered to.

PMID- 30199929
TI  - 'Over the counter' (OTC) opiate abuse treatment.
AB  - OBJECTIVES: Over the counter (OTC) medication abuse is an increasing public
      health concern. We studied the clinical profiles, treatment and prevalence of
      patients admitted with OTC opiate abuse. METHOD: Using a specially designed
      demographic form, the records of patients admitted to St. Patrick's Hospital, a
      280 bed inpatient mental health and addiction treatment facility in Dublin, with
      a diagnosis of harmful OTC opiate abuse or opiate dependency as defined in ICD-10
      were reviewed retrospectively. All patients diagnosed with OTC opiate abuse (ICD
      F11.1) or dependency (ICD F11.2) on admission to our centre were included in the
      study. Patients with a diagnosis of primary illicit opiate misuse were excluded.
      RESULTS: Approximately 1% (n=20) of inpatients admitted in a year were diagnosed
      with OTC opiate abuse. The average daily codeine intake was 261.0 mg per person.
      Some 75% percent (n=15) of the inpatients experienced OTC opiate withdrawal and
      were treated with protocol driven withdrawal regimes for an average of 16.10
      days. The female: male ratio was nearly 2:1 with an average age of 49.2 years.
      Patients tended to have co-morbid psychiatric (n=19, 95%), physical (n=17,85%)
      and polysubstance (n=13,65%) illness. CONCLUSIONS: OTC opiate abuse is a
      significant problem which is largely covert in nature with serious co-morbidity
      and frequent complications including withdrawal symptoms which require treatment.
      Results of this study suggest that further research is warranted in this area.

PMID- 30199930
TI  - The use of inpatient services in patients with borderline personality disorder.
AB  - OBJECTIVES: To examine why five patients with borderline personality disorder
      were contributing to a high bed occupancy and high staff turnover on a general
      adult psychiatry inpatient unit. METHOD: A retrospective audit looking at these
      individuals' service pattern use for the two-year period between 2001-2003 was
      undertaken. A new admission policy was then introduced. The policy was that
      admissions were agreed, where possible, at consultant level and, if deemed
      unavoidable, were time limited. The audit cycle was repeated for the next two
      year period, 2003-2005 and a third audit cycle was then performed for the period
      2005-2007. RESULTS: Following the new admission policy, there was a 95% reduction
      in bed days for this group. Untoward incidents by these individuals reduced by
      93% and attendance at Accident and Emergency was also significantly reduced.
      CONCLUSIONS: By limiting the frequency and length of admissions there was,
      unsurprisingly, a reduction in adverse incidents which lead to significant
      problems for patients and staff alike.

PMID- 30199931
TI  - Estimating the prevalence of adult ADHD in the psychiatric clinic: a cross
      sectional study using the adult ADHD self-report scale (ASRS).
AB  - OBJECTIVES: We sought to determine the point prevalence of adult attention
      deficit/hyperactivity disorder (ADHD) in an out-patient psychiatric population.
      METHODS: Patients (n=243) attending five different outpatient clinics in a
      largely urban adult psychiatric service completed the Adult ADHD Self-Report
      Scale, a recently developed instrument by the World Health Organisation. Clinical
      and demographic data were recorded. RESULTS: There was a high apparent rate of
      adult ADHD detected (23.9%). Such patients were significantly more likely to have
      lower educational attainment, ADHD as children, a forensic history and the
      diagnosis of personality disorder as well as a higher rate of benzodiazepine use.
      They were no more likely to be dissatisfied with the service, nor to be heavier
      users of the service. CONCLUSIONS: We report a high apparent rate of adult ADHD.
      Correlates of this high rate indicate individuals with less positive lifestyles
      than other patients. Screening for this disorder appears warranted, particularly
      in the light of the emergence of new non-amphetamine-based therapies.

PMID- 30199932
TI  - Suicide in Ireland: a cross-national view.
AB  - Recent epidemiological trends in Irish suicide rates were examined and found to
      be consistent with worldwide trends. However, the time-series Irish suicide rate
      was not consistent with predictions made from Durkheim's classic theory of
      suicide. Finally, current theories of the etiology of suicide were used to derive
      a linear regression equation to predict the Irish suicide rate which turned out
      to be quite inaccurate. The task addressed in this article is a review of the
      epidemiology of suicide in Ireland and, in doing so, the suicide rate in Ireland
      will be compared with the suicide rates of other nations of the world. Table 1
      reports the suicide rate in Ireland from 1901 to 1949, Table 2 for the period
      1950-2001, overall and for men and women (and parallel data for Northern Ireland
      are shown in Table 3). These data were compiled from Lester and Yang and from
      World Health Organisation publications and online (www.who.int). It should be
      noted that suicide was decriminalised in Ireland in 1993.

PMID- 30199933
TI  - Catatonia - case report and review.
AB  - Catatonia is a neuro-psychiatric disorder that can occur in medical, psychiatric
      and drug-induced conditions but is often unrecognised. A 64 year-old woman was
      admitted to hospital for assessment of a significant deterioration in her ability
      to communicate and function normally so that she had become completely dependent
      on others for all activities of daily living for nearly three years. Outpatient
      medical and psychiatric assessments failed to clarify diagnosis. On admission to
      a general hospital, the neurology team initially believed she had a Parkinson's
      like syndrome but after further investigation and comprehensive multidisciplinary
      assessment, including neuro-psychiatric review, she was diagnosed with catatonia.
      She was subsequently admitted to a psychiatric hospital where she received
      electro-convulsive therapy and changes to her psychotropic medication regimen.
      She responded well to treatment and within a short period of time was able to
      function independently again.

PMID- 30199934
TI  - Early intervention in psychosis: service models worldwide and the Irish
      experience.
AB  - This paper examines the concept of early intervention in psychosis at primary and
      secondary prevention levels. Examples of early intervention service models from
      different countries are presented and we discuss current evidence for efficacy.
      We highlight the Irish experience of early intervention to date, and discuss
      future implementation of early intervention services in Ireland.

PMID- 30199935
TI  - Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leucoencephalopathy (CADASIL): a familial cause of depression and headache.
AB  - A 31 year-old man with a history of a depressive episode presented with acute
      severe 'thunderclap' headache. Magnetic resonance imaging (MRI) revealed
      abnormalities typical of cerebral autosomal dominant arteriopathy with
      subcortical infarcts and leucoencephalopathy (CADASIL), which was subsequently
      confirmed by genetic analysis. The psychiatric features of this genetic cause of
      depression and headache are discussed.

PMID- 30199936
TI  - Risperidone induced periorbital oedema.
AB  - Antipsychotic medications are associated with adverse cutaneous reactions (ACRs)
      in approximately 2-3% of patients. We present three cases of possible risperidone
      induced periorbital oedema in the absence of any other systemic or local cause
      responsible for the oedema. The development of periorbital oedema after the
      initiation of risperidone therapy, and disappearance after the discontinuation of
      this drug, suggests a possible causal relationship between periorbital oedema and
      risperidone. To our knowledge, there are very few reports of risperidone therapy
      and development of periorbital oedema. Risperidone is a valid and effective
      choice amongst antipsychotic medications, but these cases call for caution
      regarding ACRs at the time of prescribing.

PMID- 30199937
TI  - Phone prompts to improve attendance at a new patient clinic.

PMID- 30199938
TI  - Fetal alcohol spectrum disorders - an Irish perspective.
AB  - The impact of prenatal alcohol exposure is far reaching and transgenerational but
      is largely under diagnosed. This has been a major public health concern but
      remains an area that has lacked attention with regards service development and
      research in Ireland. There is a need for mental health professionals to have a
      good working knowledge of the range of deficits associated with prenatal alcohol
      exposure. Knowledge of these deficits will facilitate identification of affected
      children for early diagnosis and intervention. This paper reviews available
      literature on this topic using broad search criteria. The aim of this article is
      to create greater awareness among professionals working with children in Ireland
      considering the high rates of alcohol consumption and the fact that most cases of
      FASD present with chronic undiagnosed mental health problems.

PMID- 30199939
TI  - Editorial - IJPM Spring 2013.

PMID- 30199941
TI  - Planning dementia services: new estimates of current and future prevalence rates
      of dementia for Ireland.
AB  - OBJECTIVES: The paper provides new estimates of dementia prevalence at a national
      and local level in Ireland and new projections of future numbers of people with
      dementia. METHODS: The prevalence of dementia at a national and local level has
      been calculated by applying European Collaboration on Dementia (EuroCoDe)
      prevalence rates to data from the Census of Population 2006. The National
      Disability Survey has been used to estimate the number of people with Down
      syndrome and dementia. Projections of future numbers of people with dementia have
      been calculated by applying EuroCoDe prevalence rates to the most recently
      available population projections from the Central Statistics Office (CSO).
      RESULTS: It is estimated that there were 41 740 people with dementia in Ireland
      in 2006. Estimates show that there are clear regional differences in prevalence
      of dementia across Ireland, with the largest proportion of people with dementia
      in the West of Ireland, and the Dublin North Eastern region having the lowest
      share of dementia. Our best estimate is that there are 700 people with Down
      syndrome and dementia in Ireland. Applying EuroCoDe prevalence rates to the most
      recent CSO population projections shows that the prevalence of dementia in
      Ireland will increase to between 67 493 and 70 000 in 2021 and to between 140 580
      and 147 000 in 2041. CONCLUSIONS: Although there are several limitations to these
      estimates, the data provide timely and useful information for planning effective
      health and social care services, as well as raising public and professional
      awareness about dementia at a national level.

PMID- 30199940
TI  - Use of codeine-containing medicines by Irish psychiatric inpatients before and
      after regulatory limitations on their supply.
AB  - BACKGROUND: In recent years, concerns have been highlighted in several
      jurisdictions, including Ireland, regarding abuse of over-the-counter codeine
      containing medicines. On the 1st of August 2010, national regulatory guidelines
      aimed at limiting the supply of these medicines in Ireland came into force. Aims
      To study the effects of the new regulations on the use of non-prescribed codeine
      containing medicines by psychiatric patients admitted to an Irish university
      teaching hospital before (n = 117) the regulations came into effect and 6 months
      afterwards (n = 126). METHODS: Participants completed a brief self-administered
      survey questionnaire about their use of over-the-counter codeine-containing
      medicines in the preceding 3 months. RESULTS: Compared with before the
      introduction of the new regulations, there was a large decline in the reported
      'often' or 'regular' use of codeine-containing medicines in the 3 months before
      admission (33.3% v. 17.4%, chi 2 = 6.354, p = 0.01) and there was a reduction in
      the proportion of patients for whom others had expressed concerns about their
      frequency of use of such medications (15.5% v. 4.8%, chi 2 = 7.29, p = 0.03).
      There was also a decline in the proportion of patients who stated that they would
      use codeine-containing medicines for either a 'feel-good' effect or to curb
      cravings (15.9% v. 1.9%, p < 0.01, two-tailed Fisher's exact test). CONCLUSION:
      We conclude that tight regulations on the supply of non-prescription codeine
      containing medicines have the potential to reduce the use and abuse of such
      medicines in patient populations availing of admission to psychiatry hospitals.

PMID- 30199942
TI  - Smoking-related prospective memory deficits observed on naturalistic everyday
      memory task.
AB  - OBJECTIVE: This study assessed self-reported and objective prospective memory
      (PM) processes in smokers and a never-smoked comparison group. If persistent
      smoking does impair PM, then one would expect smokers recall being lower on a
      study that requires them to remember everyday activities when compared with a
      never-smoked group. METHOD: An existing-groups design was used to compare a group
      of smokers with a never-smoked group on the self-report Prospective Memory
      Questionnaire (PMQ) and the Prospective Remembering Video Procedure (PRVP)
      measuring objective PM. An example of the location-action combination from the
      PRVP is 'At Thornton's shop' (location), 'Buy a bag of sweets' (action).
      Participants who reported using an illegal substance (e.g. ecstasy, cannabis),
      who drank excessively or were 'binge drinkers', or who reported suffering from a
      clinical condition, such as depression, were excluded from the study. Age, weekly
      'safe levels' alcohol use, and strategy use were also measured and controlled for
      in the study. Each person was tested individually in a quiet laboratory setting
      on a university campus. RESULTS: After controlling for variations in age, weekly
      alcohol use, and strategy use, smokers recalled significantly fewer location
      action combinations on the PRVP when compared with a never-smoked group, with no
      between-group differences on self-reported PM as measured by the PMQ.
      CONCLUSIONS: The findings suggest objective PM deficits are associated with
      persistent smoking - a relatively unexplored area of research. This cannot be
      attributed to other drug use, mood, or strategy use. The findings also suggest
      smokers lack self-awareness of such PM deficits. This study extends the area by
      utilising a more naturalistic object measure of PM and incorporating strict
      controls into the study.

PMID- 30199943
TI  - Computerised cognitive behavioural therapy: helping Ireland log on.
AB  - OBJECTIVES: The aim of this article is to review and highlight evidence-based
      computerised cognitive behavioural therapy (cCBT) programmes that can potentially
      be used in Ireland for the treatment of mild-to-moderate mental health
      difficulties. METHODS: The authors undertook a literature search using three
      databases, and consulted a recognised, university-developed web portal. For a
      programme to be included in this review, it had to (a) have at least one
      randomised controlled trial demonstrating its efficacy; (b) be available on the
      internet; and (c) be delivered in English. Findings Twenty-five cCBT programmes
      that met the inclusion criteria were profiled. Taken together, these programmes
      target various anxiety difficulties (i.e. generalised anxiety, panic/phobia,
      social anxiety and post-traumatic stress), depression (or low mood), eating
      problems, stress, insomnia, pain and alcohol misuse. CONCLUSIONS: cCBT
      programmes, preferably administered as part of a stepped-care model, offer
      effective, low-cost and low-intensity interventions for a wide range of
      psychological problems. Their use could be beneficial given how underdeveloped
      primary care mental health services are in Ireland.

PMID- 30199944
TI  - A qualitative study of the perceived impact of a community mobilisation
      intervention to reduce alcohol consumption among amateur sportsmen.
AB  - : Aim The aim of this study was to examine the perceived impact of a community
      mobilisation intervention programme to reduce alcohol consumption among amateur
      sportsmen aged 16-34 years. METHOD: A qualitative focus group format was used to
      identify potentially important themes or concepts relating to players' and
      coaches' experiences of the intervention. Six focus groups were conducted (five
      with four to seven players per focus group and one with six coaches) to elicit
      participants' experiences of the intervention. RESULTS: Three major themes
      emerged from the analyses: patterns of alcohol consumption and associated
      factors; perceived impact of the intervention; and suggested changes to the
      community mobilisation intervention. Excessive binge drinking (i.e. the
      consumption of six or more standard drinks on any one occasion) was common among
      players. The perceived impact of the intervention programme among players was
      low; players and coaches believed that if future programmes were to succeed, a
      'bottom-up' rather than a 'top-down' approach should be adopted. CONCLUSIONS: The
      findings suggest that players perceived the community mobilisation programme to
      have had only limited success in changing attitudes or behaviour towards alcohol
      consumption in this amateur sports setting.

PMID- 30199945
TI  - Mental health knowledge and attitudes in a transition year student group: a pilot
      survey.
AB  - : Introduction Stigma towards mental health disorders remains a significant
      problem in society. Numerous public awareness campaigns and, to a lesser extent,
      educational interventions have been carried out to date to help address this
      issue. METHOD: A brief questionnaire was formulated and administered to two small
      groups of transition year students from schools throughout Ireland who
      participated in a week-long placement in a Psychiatric Hospital in Dublin in
      2012. The input was from psychiatry and allied health professionals covering a
      wide range of mental health topics. It was administered before the first session
      and immediately after the last session. The input for each group in terms of
      topics was almost identical. RESULTS: In all, 24 students participated, and the
      majority had either gone to school with, had observed in passing, or had a friend
      of the family or a relative with a mental illness, although only 21% had had
      knowledge on mental illness up to the intervention. The post-intervention scores
      demonstrated that the week had an impact on most of these views. Their attitudes
      to individuals with mental illness as regards employment, treatment, assistance,
      and recovery were encouraging, even at baseline, and all their responses improved
      following the sessions. There was a view that those with mental illness were
      somewhat reluctant to seek professional help. CONCLUSIONS: Although the results
      of this study are very encouraging as regards attitudes towards mental health and
      their response to education, far more research and interventions are needed to
      explore and address stigma in more detail.

PMID- 30199946
TI  - Refractory mania and inability to consent: an important role for involuntary ECT.
AB  - We present the case of a 23-year-old man with a first episode of severe mania,
      which was refractory to pharmacotherapy. The case demonstrates a rapid response
      and full recovery after the use of electroconvulsive therapy (ECT). The ECT was
      administered involuntarily under Section 59(1) (b) of the Irish Mental Health Act
      2001 as the patient was unable to consent to the treatment. The case highlights
      the benefits of ECT for this serious condition and emphasises the importance of
      retaining the legislative capacity to provide such an effective treatment for
      patients unable to consent because of severe psychotic illness.

PMID- 30199947
TI  - Research in young people at ultra-high risk for psychosis: a review of the
      current evidence.
AB  - BACKGROUND: The past 15 years have seen a growing interest in early intervention
      and detection of psychosis before the onset of the first episode. Recent
      proposals to include a psychosis risk syndrome (PRS) in DSM 5 have focused
      attention on the evidence base achieved to date in this field. Aims This article
      aims to (1) review the underlying principles of early identification and
      intervention during the pre-psychotic phase, (2) summarise the naturalistic
      follow-up studies conducted to date in this 'at-risk' population, (3) discuss the
      identified clinical risk factors for transition to psychosis, (4) summarise the
      interventional studies both psychological and pharmacological completed to date
      and (5) briefly discuss the controversy around the proposed inclusion of the PRS
      in DSM 5. METHODS: Electronic databases EmBase, MedLine and PsychInfo were
      searched using the keywords ultra-high risk/at-risk mental state/risk
      syndrome/pre-psychotic/prodrome/prodromal and psychosis/schizophrenia. RESULTS:
      The evidence suggests that it is possible to identify individuals who may be at
      risk of developing psychosis. Results from intervention studies, mostly involving
      second-generation antipsychotics and cognitive behavioural therapy, are currently
      insufficient to make treatment recommendations for this group. The emerging
      research with regard to possible neuroprotective factors such as omega fatty
      acids is promising, but will require replication in larger cohorts before it can
      be recommended.

PMID- 30199948
TI  - Correspondence.

PMID- 30199949
TI  - Correspondence.

PMID- 30199950
TI  - The Challenge of Managing Severely Ill Patients with Anorexia Nervosa in Ireland.
AB  - Anorexia Nervosa (AN) has the highest rates of morbidity and mortality of any
      psychiatric disorder. Psychiatrists in Ireland have reported difficulties in
      managing patients with AN, particularly those with severe levels of illness. This
      paper explores these management difficulties, including the financial and
      organisational impediments to service provision, and the legal and ethical
      dilemmas involved in dealing with those patients who refuse treatment.

PMID- 30199951
TI  - Situational and psycho-social factors associated with relapse following
      residential detoxification in a population of Irish opioid dependent patients.
AB  - AIMS: To identify and describe the context and factors involved in the opioid
      lapse process following discharge from an Irish inpatient opioid detoxification
      treatment programme. Design, participants, setting: Prospective follow-up study
      of consecutive detoxified opioid dependent patients treated in a specialist
      inpatient drug dependency unit. MEASUREMENTS: The Maudsley Addiction Profile and
      a structured interview were administered to 109 patients, 18-36 months after
      discharge. FINDINGS: Of 109 people interviewed at follow-up, 102 (94%) reported
      at least one episode of opioid use after leaving the residential treatment
      programme. Eighty eight patients (86% of the lapsers) identified more than one
      major factor contributing to their recidivism. The median number of factors
      identified as having a major role in the lapse was four. The most frequently
      reported major contributors to lapse were low mood (62%), difficulties with
      craving (62%), ease of access to heroin (48%) and missing the support of the
      treatment centre (43%). CONCLUSIONS: Early lapse was common following inpatient
      treatment of opioid dependence. Lapse tended to result from a number of common,
      identifiable, high-risk situations, feelings and cognitions which may assist
      clinicians and patients develop lapse prevention strategies to anticipate and
      interrupt this process.

PMID- 30199952
TI  - Suicide on the Isle of Wight: A Case-study of 35 Suicides among Mental Health
      Service Users Between 2006 and 2008.
AB  - AIMS: To identify the sociodemographic, clinical and service delivery risk
      factors for suicide in psychiatric patients in a limited geographic area. METHOD:
      A retrospective case study of 35 patients who died as a result of suicide between
      January 2006 and December 2008. RESULTS: Male gender, unemployment, living alone,
      basic education and significant life events were identified as sociodemographic
      factors. A history of previous psychiatric admission, previous suicide attempt,
      suffering from depression, co-morbidity of another psychiatric disorder (mainly
      stress-related symptoms and alcoholism), and contacting the services prior to
      suicide were found as typical clinical factors. Hanging was the most common
      method of suicide in both men and women. Most men died in spring and summer,
      while the majority of females died in autumn. CLINICAL IMPLICATIONS: As in
      similar studies, mental disorders could be identified as the strongest risk
      factor for suicide. Almost 70% of suicides were conducted by people suffering
      from a mental disorder. Treating mental disorders and identifying certain
      sociodemographic and clinical characteristics of people suffering from mental
      disorders and addressing them is the key in suicide prevention strategies.

PMID- 30199953
TI  - Patients' Satisfaction with a Psychiatric Day Hospital in the West Galway
      Catchments Area.
AB  - AIM: To evaluate patients' satisfaction with a psychiatric day hospital in the
      West Galway Catchments area. STUDY DESIGN: This is a cross-sectional study.
      METHODS: This study was undertaken by using a 33-items questionnaire for 44
      patients who attended the day hospital. SPSS version-12 was used for collecting
      and applying tests to the data, Fisher's exact test was used to analyse the data
      as sample size is small and P<0.05 was considered statistically significant.
      Results are also presented in the form of descriptive analysis including
      percentages and frequencies. RESULTS: Only 37 out of the 44 patients returned the
      questionnaires. Among the participants were 61% (n=22) male and 38% (n=15)
      female. The patients were mostly satisfied with the services available at the day
      hospital, except the waiting period for a first appointment. There was no
      significant (P=0.11) gender difference in terms of patients' satisfaction with
      the day hospital service. The age group, 45 years and above, were less satisfied
      (P=0.02) with the availability of a comfortable room for counselling, as compared
      to the younger age group. The patients did not like to tell others that they were
      attending the day hospital. The results were comparable with previous published
      patient satisfaction surveys using the same questionnaire by the Health Research
      Board, except that the patients in the present survey were more satisfied with
      the waiting area and availability of counselling. CONCLUSIONS: Patients are
      mostly satisfied with the West Galway day hospital services. The older patients
      (45 years and above) are not satisfied with the counselling room, and therefore
      further investigations are needed to ascertain their requirements for a
      counselling room. Patients are more satisfied with the waiting area and
      availability of counselling compared to the findings of other similar studies
      conducted in Ireland. Resources are needed to be allocated to the day hospital
      services.

PMID- 30199954
TI  - Psychiatrists: An Endangered Species? A Study to Observe Attitude of Fifth Year
      Medical Students to Psychiatry and to Compare Change in Same after a Psychiatry
      Posting During Medical School.
AB  - OBJECTIVE: This study was conducted to gauge the attitude of fifth year medical
      students to psychiatry as a potential career choice and to determine if an eight
      week clinical attachment had any impact on this. METHODS: We surveyed a cohort of
      fifth year medical students from Trinity College Dublin. A purpose designed, self
      completed questionnaire was used to establish a number of variables and was given
      to students on the first and last day of their attachment in psychiatry.
      Participation was optional and responses were confidential. Questionnaires were
      distributed following an explanation of the purpose of the study. RESULTS: The
      survey was applied to 118 fifth year medical students. The most significant
      finding of the study was the increase in number of students choosing psychiatry
      (17%) as a possible career upon completion of the attachment as compared to
      before (4%). The majority of the students considered psychiatry as a mainstream
      specialty with little change in this perception pre and post attachment. Almost
      all of the students believed that a psychiatry posting would improve their
      communication skills when dealing with patients. Approximately half of students
      chose medical subspecialties as career choice prior to their psychiatry posting
      but this declined afterwards. There was a small increase in the number of
      students wanting to become GPs and those who were undecided about their potential
      career choice. With regards to deterrents to doing psychiatry, the principal one
      was the belief that psychiatry was too depressing and stressful. Lack of
      interest, adverse career prospects and financial considerations featured in a
      minority of student answers. CONCLUSIONS: The findings of this study suggest that
      psychiatry remains less attractive to students as a career compared to some other
      specialities but a clinical attachment may be an important means of raising
      interest in psychiatry as a career.

PMID- 30199955
TI  - Decreased Verbal Learning but not Recognition Performance in Alcohol-dependent
      Individuals During Early Abstinence.
AB  - OBJECTIVE: Alcoholism ultimately leads to impairment of memory and other
      cognitive functions. This can interfere with treatment, if cognitively impaired
      alcohol-dependent individuals have difficulties recalling and implementing skills
      acquired during therapy. We investigate if alcohol-dependent individuals without
      clinically apparent withdrawal symptoms may still be impaired in higher-order
      cognitive functions. METHODS: Thirty-four alcohol-dependent patients and 20
      matched healthy controls were tested with the Verbal Learning and Memory Test
      which includes seven measurement points. The test comprises free recall, free
      recall after distraction and after 30 minute delay, and a word recognition task.
      Testing was performed between day seven and day 10 after the beginning of
      abstinence, when clinical withdrawal symptoms had ceased. RESULTS: Compared to
      healthy controls, alcohol-dependent patients performed worse in free recall after
      delay, but not in word recognition. Healthy controls showed a more linear
      progression of improvement in verbal memory performance. Overall, alcohol
      dependent individuals showed reduced verbal learning efficiency. The extent of
      impaired recall after distraction was positively associated (one-tailed test)
      with history of delirium (r=0.34, p=0.04), seizures (r=0.46, p=0.01), and years
      since diagnosis for alcohol dependency (r=0.39, p=0.01). CONCLUSIONS: Our results
      provide evidence that unmedicated alcohol-dependent patients without obvious
      withdrawal symptoms had impaired verbal recall, but normal recognition
      performance, at seven to 10 days after onset of abstinence. This deficit may
      deteriorate treatment outcomes due to poorer implementation of skills newly
      learned during this time period.

PMID- 30199956
TI  - Post-Traumatic Stress Disorder (PTSD) Symptoms in Adults with Psychiatric
      Disorders.
AB  - OBJECTIVE: This study explores unrecognised symptoms related to post-traumatic
      stress disorder (PTSD) in individuals with a range of psychiatric disorders in
      the absence of traumatic events. We also examine the association between PTSD
      symptoms, social interaction with peers and therapeutic alliance with mental
      health professionals. METHOD: A purposive sample of 120 adults consecutively
      referred to the psychology department from September 2008 to September 2010 was
      included in this study. We used the Minnesota Multiphasic Personality Inventory 2
      (MMPI-2) to ascertain the presence of PTSD symptoms, social interaction levels
      and treatment alliance with health professionals. RESULTS: Individuals previously
      undiagnosed with PTSD, referred without any noted traumatic event had high levels
      of symptoms related to PTSD, as measured by the PK scale of the MMPI-2. The PK
      scale was significantly correlated with several MMPI-2 clinical scales, the
      Social Introversion Scale (Si) and the Treatment Alliance Scale (TRT) (p <
      0.001). CONCLUSION: This study demonstrated the presence of symptoms related to
      PTSD in individuals with a range of psychiatric disorders despite the absence of
      reported trauma. The presence of symptoms related to PTSD may be associated with
      an indirect negative impact on social contacts and a poorer therapeutic alliance
      with mental health professionals. Investigating symptoms of PTSD during a
      psychological assessment even when trauma is not the presenting complaint is
      merited in most cases.

PMID- 30199957
TI  - Child and Adolescent Mental Health Services in Laois/Offaly: A One Year
      Perspective of Services (July 1, 2008 to June 30, 2009).
AB  - OBJECTIVES: To examine the Laois/Offaly Child and Adolescent Mental Health
      Services (CAMHS), focusing on new referrals and trends in the service. METHODS:
      Data was collected over a one-year period from July 1, 2008 to June 30, 2009
      using the computer system MAISY (Medical Audit Information System) and through
      chart reviews. A Client Satisfaction Survey was administered to both parents and
      children. RESULTS: The Laois/Offaly CAMHS team provides service to a total
      population of around 140,000, of which around 32,000 are less than 16 years old.
      In this one-year period, 303 referrals were received with 167 offered an
      assessment, of which 150 availed of an appointment. Forty-six percent were
      offered appointments within one week of receiving the referral with 87% being
      assessed within one month. A further 41 were assessed from a previous waiting
      list, compiled prior to the actual study period, thus resulting in a total of 191
      assessments. Thirty referrals required assessment only. Behavioural/Emotional
      difficulties and Attention Deficit Hyperactivity Disorder (ADHD) were the most
      common reason for referral. During this time the ADHD waiting list was suspended
      due to staff constraints. Seventy-six percent were diagnosed with an Axis I
      disorder with 34% given medication treatment. Of the return appointments over the
      year, eight percent of patients did not attend (DNA). Both parents and children
      reported being satisfied with the service, according to the Client Satisfaction
      Survey. CONCLUSIONS: The Laois/Offaly team services a catchment area of
      approximately three times the number recommended by A Vision for Change, with a
      staff equivalent less than the number recommended for one whole team. The team
      was able to provide a rapid service for assessment of new referrals, with the
      ADHD waiting list suspended. Axis I pathology was often diagnosed among those
      assessed (around 75%), with about one-third being treated with medication. Follow
      up appointments achieved a high attrition rate, with only around eight percent
      not attending. Patient satisfaction with the service rated high by both parents
      and children.

PMID- 30199958
TI  - The Vron - An Early Intervention In-patient Recovery Unit.
AB  - BACKGROUND AND AIMS: This paper describes the context in which the Vron, a six
      bedded 24-hour nursed care unit, has developed its role from a fast track
      rehabilitation unit, to work explicitly within an early intervention service. The
      study aimed to evaluate the work of the Vron by examining the change in CANSAS,
      HoNOS and EM scores between admission to and discharge from the unit. RESULTS:
      Approximately half of the admissions to Vron were from acute psychiatric wards.
      Most patients were discharged to their own tenancy or supported accommodation.
      There was a significant reduction in mean HoNOS score and increase in mean EM
      score during admission. Mean staff and patient-rated unmet needs reduced in the
      course of admission. In the course of admission, approximately half of the
      patients developed occupational roles. DISCUSSION AND CONCLUSIONS: The findings
      of this service evaluation must be interpreted with caution in view of the
      methodological limitations, in particular the lack of a comparator service
      intervention. However, it is suggested that units of this type may have a useful
      role in the rehabilitation of patients with complex severe mental illness,
      particularly if deployed at an early stage in an individual's illness, to prevent
      development of disability. The Vron focuses on a number of specific clinical and
      social areas which align with typical strategies in early intervention.

PMID- 30199959
TI  - Knowledge and Attitude of Basic Psychiatric Trainees in Ireland to the Clinical
      Indemnity Scheme.
AB  - OBJECTIVES: To assess the knowledge of basic psychiatric trainees in Ireland of
      the Clinical Indemnity Scheme (CIS) and to ascertain how many basic specialist
      trainees in psychiatry had obtained additional medical indemnity cover and
      reasons for obtaining additional cover. METHOD: A structured questionnaire was
      distributed by post to 300 basic specialist trainees in psychiatric training
      schemes in Ireland. The questionnaire enquired about demographic details and
      examined the level of trainees' knowledge of the clinical indemnity scheme.
      Results were compiled and analysed using descriptive statistics and SPSS version
      14. RESULTS: The response rate was 49%. The bulk of respondents were male
      (65.5%), aged between 30-35 years of age (44.6%). The majority of the respondents
      were aware of the CIS, with approximately half of the respondents having acquired
      additional medical indemnity cover. The level of awareness of the CIS was
      proportionately more amongst male respondents (69.1%), compared with females
      (58.5%). However, more females (61.5%) had additional medical indemnity cover
      compared with males (45.5%). Irish national trainees were more aware (72.9%) and
      had additional medical indemnity (80%), compared with non-Irish national trainees
      of whom approximately 61% were aware of the CIS and only 40% had an additional
      cover. The level of knowledge regarding details of what the CIS provided coverage
      for was quite poor. Respondents who had obtained additional indemnity were unsure
      what cover their additional indemnity provided. Only 10 respondents had been
      involved in medico-legal cases and of these, five had medical indemnity at the
      time of the case, stating that the legal advice and support was helpful.
      CONCLUSION: Our survey has highlighted that a considerable number of basic
      specialist trainees in psychiatry in Ireland had no detailed knowledge of what
      the CIS indemnifies them for and what situations were not covered by the scheme.
      Additionally, it revealed a clear split in favour of Irish national trainees in
      comparison to non-Irish national trainees in terms of awareness of the CIS and
      the procurement of additional medical indemnity. There needs to be an educational
      drive to provide more information to psychiatric trainees regarding the CIS and
      other medical insurance schemes. Furthermore, it would be important to examine
      factors that influence trainees in obtaining/not obtaining additional cover.

PMID- 30199960
TI  - Experience of an Inter-regional Research Symposium for Higher Psychiatric
      Trainees in Scotland.
AB  - OBJECTIVES: We present our experience of an annual research symposium for
      psychiatric trainees in Scotland. This paper aimed to consider trainees'
      involvement in research by examining firstly rates of publication and secondly
      the views of trainees. METHODS: A list of all presentations to the Senior
      Trainees' Annual Research Symposium (STARS) meetings 2007-2009 was compiled and a
      detailed search made of major research databases. A questionnaire survey examined
      the views of attendees at the 2009 meeting. RESULTS: Fifty percent of presented
      work achieved publication. Feedback from symposia attendees was almost
      universally positive. CONCLUSIONS: At a time of debate on the value of research
      sessions as part of higher training and a recent reduction in time allocated to
      research in the UK, we report on a thriving annual meeting. Research symposia for
      higher trainees were valued by participants and may be one useful means of
      encouraging trainee research.

PMID- 30199961
TI  - Delayed Onset of Neuropsychiatric Effects Associated with Montelukast.
AB  - Montelukast (a leukotriene receptor antagonist) is a commonly prescribed
      medication used in the management of asthma in both children and adults. It has
      been associated with a possible increased risk of various neuropsychiatric events
      in post-marketing analyses of clinical trial data and surveillance studies. When
      establishing a link between a medication and side effects, it is usual to
      establish and enquire whether there is a chronological relationship between the
      commencement of the medication and the onset of the symptoms. We report a case
      where a number of unusual neuropsychiatric events were reported several years
      after commencement of montelukast in a young boy who may have a genetic
      predisposition and a likely psychological trigger. There was complete resolution
      of these symptoms upon the withdrawal of montelukast.

PMID- 30199962
TI  - Benzodiazepine and Z-drug Prescribing for Elderly People in a General Hospital: A
      Complete Audit Cycle.
AB  - BACKGROUND: Use of benzodiazepines and Z-drugs in the elderly is associated with
      adverse outcomes such as increased risk of falls and fractures and cognitive
      impairment. We aimed to assess the prescribing practice of benzodiazepine and Z
      drugs in those aged over 65 years in a general hospital against evidence based
      standards and to examine the effects of multidisciplinary feedback, as well as
      determine the prevalence of usage. METHODS: All case-notes and medication charts
      of patients over the age of sixty five on surgical and medical wards in Sligo
      General Hospital (SGH) were retrieved and analysed over a two-day period in 2008.
      Data was collected in relation to benzodiazepine and Z-drug prescribing. We
      followed up on this initial data collection by screening discharge summaries at
      six weeks to assess benzodiazepine and Z-drug prescribing on discharge. Audit
      results were disseminated together with consensus guidelines on the prescribing
      of these medications in older adult population to all general practitioners in
      County Sligo. Educational sessions were held for both doctors and nurses in SGH.
      The audit cycle was completed by a re-audit of benzodiazepine and Z-drug
      prescribing six months from original study using identical methods. RESULTS: We
      found a high prevalence of benzodiazepine and Z-drug use in original audit, 54%
      (38/70) of the group audited. The prevalence fell to 46% (32/70) at the re-audit
      post intervention. This result was not statistically significant. The percentage
      of patients commenced on benzodiazepine and Z-drugs prior to admission fell from
      36% (25/70) at the initial audit to 23% (16/70) at the re-audit. CONCLUSION:
      Prescribing practices were not in keeping with consensus guidelines as
      highlighted by this relatively basic audit cycle. Multidisciplinary feedback and
      letters to GPs resulted in some reduction in the number of patients prescribed
      benzodiazepines and Z-drugs. Ongoing educational strategies aimed at relevant
      health care workers with regular audit of medication use within the general
      hospital setting is pertinent to further improve prescribing practice.

PMID- 30199963
TI  - Threshold Concepts and Teaching Psychiatry: Key to the Kingdom or Emperor's New
      Clothes?
AB  - Psychiatry, more than most medical specialties, must engage with undergraduate
      medical education to prevent the further marginalisation of mental health within
      medicine. There is an urgency to the need for psychiatrists and educationalists
      to communicate, and for psychiatrists to be aware of developments in educational
      theory. The idea of 'threshold concepts' is currently widely discussed by
      educationalists. Threshold concepts are described as areas of knowledge without
      which the learner cannot progress, and which, when grasped, lead to a
      transformation in the learner's perspective and understanding. Threshold concepts
      have been criticised on conceptual grounds, and there is a lack of clarity as to
      how to identify them empirically. While they may represent a fruitful approach to
      the task of engaging medical students in psychiatry teaching, it is suggested
      that further development of the idea is required before it could be usefully
      applied. However empirical studies in other disciplines suggest that there may be
      associated benefits to the teaching of the discipline from trying to identify
      threshold knowledge.

PMID- 30199964
TI  - Exploring Health in Census 2011.

PMID- 30199965
TI  - The Dissociative Experiences Scale: A Welsh Translation.

PMID- 30199966
TI  - Consultant attitudes to the advance statement.

PMID- 30199967
TI  - A health screening and promotion clinic to improve metabolic monitoring for
      patients prescribed antipsychotic medication.
AB  - OBJECTIVES: We sought to determine whether the introduction of a health screening
      and promotion clinic might serve as a useful addition to existing services for
      patients prescribed antipsychotic medication. In particular, we wished to assess
      whether such a clinic might improve adherence to best practice guidelines. We
      also wished to determine the level of patient interest in such a clinic and how
      readily this service might be provided within the constraints of existing
      clinical resources. METHODS: We conducted an audit of outpatient records before
      and following the introduction of a health screening and promotion clinic.
      RESULTS: Of the eligible patients, 73% attended the clinic. The proportion of
      patients who had fasting blood tests within the previous 12 months increased from
      45% at baseline to 85% at follow-up (chi 2 = 14.1, p < 0.001). The proportion of
      patients with appropriate physical observations completed increased from 5% at
      baseline to 80% at follow-up (chi 2 = 46.0, p < 0.001). CONCLUSIONS: We found
      that the introduction of a health screening and promotion clinic improved
      adherence to best practice guidelines. This service was well received and readily
      provided within the constraints of existing resources. Ultimately, the structure
      of services to screen and advise patients prescribed antipsychotic medication
      will be determined by local resource considerations and configuration of
      services.

PMID- 30199968
TI  - Liberty or dignity: community treatment orders and rights.
AB  - The use of community treatment orders (CTOs) remains controversial despite their
      widespread use in a number of different countries. The focus of a CTO should be
      on individuals with severe and enduring mental disorders, typically requiring
      adherence with recommended outpatient treatment in the community and requiring
      that they allow access to members of the clinical team for the purpose of
      assessment. There is no current provision for CTOs under Irish mental health
      legislation, although patients who are involuntarily detained under the MHA 2001
      (Ireland) can be granted approved leave from hospital. This provision allows for
      the patient to be managed in the community setting, though, while technically on
      leave, they remain as inpatients detained under the MHA 2001 (Ireland). This
      article describes the use of CTOs and considerations relating to their
      implementation. There is discussion of the ethical grounds and evidence base for
      their use. Ethical considerations such as balancing autonomy against health needs
      and the utilisation of capacity principles need to be weighed by clinicians
      considering the use of CTOs. Though qualitative research provides some support
      for the use of CTOs, there remains a clear lack of robust evidence based findings
      to support their use in terms of hospitalisation rates, duration of illness
      remission and improved social functioning.

PMID- 30199969
TI  - Sexual victimization and anxiety and mood disorders: a case-control study based
      on the Danish registry system.
AB  - : Aims This study aimed to examine the relationship between rape and the
      subsequent psychiatric diagnosis of any anxiety or mood disorder. METHOD: Data
      from the Danish Civil Registration System and the Danish Psychiatric Central
      Register were used to identify a sample of female victims who had visited a
      centre for rape victims during an index year and their subsequent psychiatric
      records were compared with a matched control group. RESULTS: While controlling
      for demographic variables and previous psychiatric disorders, the effect of
      sexual victimization increased the likelihood of a subsequent diagnosis of an
      anxiety disorder but not a mood disorder. CONCLUSION: Sexual victimization
      significantly increases the likelihood of experiencing an anxiety disorder, and
      therefore victims require post-assault information and support.

PMID- 30199970
TI  - A structured process for reviewing the operation of the Mental Health Act 2001 in
      an Irish mental health service.
AB  - This paper provides a description of a structured template which allows review of
      the operation of the Mental Health Act 2001 at St Patrick's Mental Health
      Services (incorporating St Patrick's University Hospital, St Edmundsbury Hospital
      and Willow Grove Adolescent Unit). These structured processes were implemented to
      ensure rigorous monitoring of all clinical governance activities associated with
      adherence to the Mental Health Act (MHA) 2001. The paper describes in detail the
      information contained in the St Patrick's Mental Health Services dashboard for
      2012. The dashboard displays the key performance indicators that are monitored
      and the paper describes how these were reviewed by the Hospital's Clinical
      Governance Committee on a weekly basis for the three approved centres. The
      dashboard has also been used by the Clinical Governance Committee to provide
      ongoing education and engagement with staff in order to improve the operation of
      the MHA 2001. The use of this structured monitoring process has allowed the
      hospital to measure adherence to the MHA 2001 and also to measure activities that
      impact directly on the care and treatment of patients detained under the Act. The
      use of structured monitoring tools (i.e. the dashboard) to review the operation
      of the MHA 2001 allows for coherent observation of key events and issues which
      can cause concern in terms of the operation of the Act.

PMID- 30199971
TI  - Cyberbullying and its effects on young adolescents: a community-based survey.
AB  - OBJECTIVES: To conduct a study looking at the prevalence and nature of Internet
      and mobile phone use in young people, focusing particularly on cyberbullying and
      its potential effects on young people's mental health. METHOD: Three secondary
      schools in an area of North Dublin were randomly selected, which included one all
      boys school, one all girls school and one co-educational school. Written
      information about the study was given to each school principal and to
      parents/carers of all first and second year students. First and second year
      students in each school from whom consent had been received were asked to
      complete two questionnaires, which included a questionnaire on cyberbullying and
      a self-report version of the Strengths and Difficulties Questionnaire (SDQ). A
      total of 130 students completed the study. RESULTS: A total of 24 (18.46%) pupils
      were cyberbullied. Of these, 13 (65% of those cyberbullied) pupils who were
      cyberbullied said that it had a negative effect on their mood, and 9 (45% of
      those cyberbullied) said that cyberbullying had a negative effect on their
      overall mental health. A statistically significant higher proportion of pupils
      who were cyberbullied scored in the Abnormal/Borderline range of the SDQ,
      compared with those who were not cyberbullied. CONCLUSION: This is the first
      study in Ireland, which looks at the potential mental health difficulties
      associated with cyberbullying. It is hoped that the information from this study
      will help to increase awareness of the effects of cyberbullying and help look at
      ways of managing cyberbullying.

PMID- 30199972
TI  - Individual care packages for people with severe mental illness: a description of
      their implementation in an English County.
AB  - BACKGROUND: This paper includes a brief review of the historical and policy
      background to a new form of supported accommodation, the Individual Care Package
      (ICP). This is a co-ordinated, individualised and flexible method to support
      people with complex mental health problems in the community. METHOD: The study
      aimed to describe the implementation of this new form of care in Gloucestershire,
      England, over a 5-year period. We aimed to audit the quality of care in the
      packages against six care standards, derived by a project steering group. Staff
      working in community mental health services and staff providing ICPs were asked
      to report their levels of satisfaction with care provision. RESULTS: A total of
      35 ICPs were developed, mostly relating to service users with severe mental
      illness. Only 60% of the community mental health team key workers were aware of
      the expected level of care. In many cases, service users were accessing support
      from day services or family alongside the ICP. Four service users were admitted,
      and four moved accommodation after going into ICPs. Overall, levels of care
      provided within ICPs tended to remain static. Trust key workers were mostly
      satisfied with the support provided in ICPs, but a range of concerns were
      expressed. ICP staff reported mostly positive views about the support that they
      received from statutory services, but also reported some concerns. CONCLUSIONS:
      ICPs appeared to be successful in enabling a number of service users with complex
      difficulties to obtain and maintain tenancies in the community. There were some
      concerns about the quality of monitoring of the ICPs and some uncertainty about
      whether ICP staff would have the skills, support and training to promote recovery
      and increasing independence of service users. There was little evidence of
      service users moving on or reduction in care over time. There is a need for good
      inter-agency working for the successful deployment of this new form of service.
      There is also a need for more research, comparing ICPs with other forms of
      supported accommodation and considering the service user experience through
      qualitative research.

PMID- 30199973
TI  - Editorial: political abuse of psychiatry in authoritarian systems.
AB  - : We are painfully aware: Psychiatry in some states of the international
      community is often used to subvert the political and legal guarantees of the
      freedom of the individual and to violate seriously his human and legal rights
      (Daes, 1986). OBJECTIVE: It can be politically convenient to incarcerate
      political opponents in a psychiatric hospital. It saves any potential political
      embarrassment that a judicial trial may present. It also undermines the
      credibility of opponents by labelling them with the stigma of being mentally
      insane. For this to occur, there has to be the acquiescence of mental health
      professionals and a subservient legal system. METHOD: This article examines the
      abuse of psychiatry in two authoritarian systems, Russia and China. Result New
      diagnostic categories such as sluggish schizophrenia were created to facilitate
      the silencing of dissenters and were a source of self-deception for psychiatrist
      to placate their consciences as they operated as a tool of oppression on behalf
      of a political system. CONCLUSION: If we do not know the past, we will be
      condemned to repeat it.

PMID- 30199974
TI  - The Irish Journal of Psychological Medicine and the College of Psychiatry of
      Ireland.

PMID- 30199975
TI  - Did the Great Irish Famine increase schizophrenia?
AB  - BACKGROUND: Evidence from regions where there have been severe dietary
      restriction suggests that individuals in utero during periods of starvation may
      subsequently be at increased risk of schizophrenia. Because Ireland was the
      location of a major nineteenth century famine an attempt has been made to
      determine whether any such evidence for famine/schizophrenia association can be
      found. METHOD: The data used derive mainly from the Annual Reports on the
      District, Criminal and Private Lunatic Asylums supplied by the Inspectors of
      Lunacy in Ireland for the relevant years. Nineteenth century diagnostic labels
      have been adjusted to conform to schizophrenia as currently understood. Evidence
      relating to a possible schizophrenia increase in famine-related emigrants is
      examined. RESULTS: There was an increase in first admission rates for
      schizophrenia of 85.7% from 1860 to 1875. Admissions for other disorders, chiefly
      melancholia, also increased. Similar admission increases were evident in other
      jurisdictions over the same period. Data relating to the mental health of famine 
      migrating Irish are sparse and of difficult interpretation. CONCLUSION: The
      evidence from available data sources attempting to link the Irish famines of the
      1840s with a subsequent increase in the incidence of schizophrenia is equivocal
      and inconclusive.

PMID- 30199976
TI  - Study of Presentations for Involuntary Admission to a Cork Approved Centre.
AB  - OBJECTIVES: To describe the characteristics of patients who present to an
      approved centre with Mental Health Act 2001 forms, and secondly, to compare those
      who were subsequently detained to those who were not detained. METHODS: Specific
      data on patients who presented to South Lee Mental Health Unit with application
      and recommendation forms for Involuntary Admission over a 22 month period was
      gathered from a retrospective case note review. Information on both groups was
      compared statistically using Graph Pad Prism software. RESULTS: 71% (n=121) of
      patients presenting for involuntary admission did so outside of normal working
      hours. Those who were not subsequently detained were more likely to have had
      their application made by the Gardai and their recommendation made by someone
      other than their own General Practitioner (GP). GPs were more likely than
      Consultant Psychiatrists to cite risk to self or others as the reason for
      involuntary admission. CONCLUSION: Although involuntary admissions most often
      occur in emergency situations, every effort should be made to ensure that those
      who are known to the patient are involved in the process of application and
      recommendation. In addition, there is a need for ongoing training and education
      of those most commonly involved, such as the Gardai and General Practitioners, as
      well as feedback to these groups when a patient presents who does not require
      involuntary admission.

PMID- 30199977
TI  - Mental illness among the homeless: prevalence study in a Dublin homeless hostel.
AB  - OBJECTIVE: To determine the prevalence of mental illness among the residents of a
      homeless hostel in inner city Dublin. METHOD: A cross-sectional survey was
      carried out among hostel residents, as previous studies have indicated that
      homeless hostel-dwelling men in Dublin constitute the largest single grouping of
      homeless Irish people. All agreeable residents were interviewed by the authors
      over an eight-week period using the Structured Clinical Interview for DSM-IV Axis
      I Disorders (SCID-I) Clinical Version. For each disorder, the current (30-day)
      and past prevalence was determined. RESULTS: A total of 38 residents were
      interviewed, resulting in a response rate of 39.2% for the study. A total of
      81.6% of residents had a current Axis I diagnosis; this number increased to 89.5%
      when combining current and past diagnoses. Only four residents had no diagnosis.
      There was considerable comorbidity between disorders, with a significant number
      of residents experiencing both mental illness and substance use problems. When
      considering lifetime diagnoses, 31.6% had a single diagnosis only; 57.9% had
      two/more diagnoses. Twelve residents (31.6%) had been admitted to a psychiatric
      hospital during their lifetime. The most prevalent disorders during the past
      month were Alcohol Dependence (23.7%), Opioid Dependence and Major Depressive
      Disorder (both 18.4%), Opioid Abuse and Alcohol-Induced Depression (both 7.9%).
      Only 23.7% of interviewed residents were attending psychiatric or addiction
      services. A significant number of residents who did not wish to participate in
      the study were identified by hostel staff as having a confirmed psychiatric
      diagnosis. CONCLUSION: The survey demonstrated a very high prevalence of mental
      disorders among homeless hostel residents. The high prevalence of dual diagnosis
      highlights the need for greater collaboration between psychiatric services and
      addiction services. The outcome also points to the importance of providing mental
      health training to emergency shelter/hostel staff. Research into the mental
      health status of the homeless should be undertaken regularly if services are to
      be planned to meet the needs of this vulnerable group.

PMID- 30199978
TI  - Preferences of dress and address: views of attendees and mental health
      professionals of the psychiatric services.
AB  - OBJECTIVES: The aim of this study was to determine the views of both individuals
      attending the mental health services (attendees) and mental health professionals
      in relation to how attendees and staff should be addressed, how attendees should
      be described, and how staff should be attired. METHODS: We surveyed 132 attendees
      of the West Galway Mental Health Services and 97 mental health professionals in
      relation to how they prefer to be addressed (first name/ title and surname/ no
      preference) the description of attendees (patient / client / service user / no
      preference) and the attire of mental health staff (casual / smart / no
      preference). We also ascertained how mental health professionals believed
      attendees would view these issues. RESULTS: Attendees preferred to be described
      as patients rather than clients or service users by all mental health
      professionals, with 46-54% of attendees preferring this term "patient" compared
      to 14-17% preferring the term "client", 11-13% preferring the term "service user"
      and 20-25% having no preference (p < 0.001). They preferred to address doctors by
      their title and surname (61%) but other mental health professionals by their
      first names (60-69%) (p < 0.001). Attendees had a strong preference for being
      addressed by their first names by all the mental health professionals (86-91%) (p
      < 0.001). Doctors preferred to be attired formally (88%), compared to nurses
      (50%) or other mental health professionals (42%) (p = 0.002). Attendees had no
      preference in relation to the attire of doctors but preferred other mental health
      professionals to be attired informally. CONCLUSIONS: The study demonstrates that
      despite the increased use of several non-medical terms to describe attendees of
      mental health services; the preferred term of attendees of the psychiatric
      services in both in-patient and out-patient settings remains 'patient'. However,
      this is not universally the case, and the ascertainment of the preference of the
      attendee at the first encounter with the health professional should be
      ascertained. We also demonstrated that attendees preferences in relation to both
      "dress and address" of doctors is significantly different to their preference for
      nurses or other allied mental health professionals; which may reflect a wish for
      a less familiar and more formal interaction with doctors.

PMID- 30199979
TI  - Psychiatrists in their eyes: Children's drawings of what a psychiatrist looks
      like.
AB  - Drawings can be used as an important tool to measure children's perception and
      emotions. Using a qualitative design, we asked a group of 24 school children (10
      boys and 14 girls) aged 11-12 to draw their impressions of psychiatrists. In the
      majority of drawings, psychiatrists were portrayed as a friendly or kind figure.
      The art work was analysed by the coordinator of the Arts Initiative in Mental
      Health, Niamh O'Connor. Psychiatrists were portrayed positively by this group of
      young people. This reflects a strong influence of the media on children's
      perception.

PMID- 30199980
TI  - Selective Mutism: A prevalence study of primary school children in the Republic
      of Ireland.
AB  - OBJECTIVE: This study was carried out to determine the prevalence of selective
      mutism (SM) in an urban school population and to assess comorbidity and family
      characteristics. METHOD: Teachers of primary schools, teaching children between
      the ages of four and 12, were sent a description of SM and asked to complete the
      selective mutism questionnaire (SMQ) if they believed a child in their class met
      criteria. Thirty-nine schools were sampled, covering a catchment area of 10,927
      children. Children who screened positive on the SMQ were offered a full
      psychiatric assessment. Parent, child and clinicians completed various rating
      scales. RESULTS: A response rate of 100% from schools was obtained. The
      prevalence rate of SM was 0.18% (20/10927). fourteen (70%) attended for further
      evaluation. All children scored within the clinical range on the Clinical Global
      Assessment Scale (CGAS), indicating moderate to severe impairment. fifty percent
      (7) reported a family history of social anxiety disorder, and 43% (6) autistic
      spectrum disorders. CONCLUSION: This is the first Irish based prevalence study of
      SM. Results indicate that SM is not as rare as previously believed. Children with
      SM were found to have significant functional impairment along with a strong
      family history of anxiety and autism.

PMID- 30199981
TI  - Psychotherapy training in Ireland: A survey of college tutors.
AB  - OBJECTIVES: Psychotherapeutic skills are essential to practice psychiatry
      effectively, but previous surveys of trainees in Ireland show that they have not
      been getting adequate training in psychotherapy. This survey of college tutors
      was carried out to coincide with the establishment of the College of Psychiatry
      of Ireland which is introducing new psychotherapy training requirements. The
      survey aims to ascertain if trainees had fulfilled the Royal College of
      Psychiatrists' psychotherapy training requirements, models of psychotherapy
      available and the availability of psychotherapy qualifications amongst
      consultants and senior registrars. METHODS: A questionnaire was posted to all
      registered tutors in the Republic of Ireland. RESULTS: The postal questionnaire
      was sent to the 62 registered college tutors in the 13 training schemes. There is
      one tutor in each training hospital. The response rate was 79%. Our survey
      reveals that no psychotherapy training was available according to 16.3% of
      tutors. Only 22.5% of tutors were aware of trainees who had met college training
      requirements in the previous two years. 79.8% of tutors reported that there were
      consultants and senior registrars with qualifications in psychotherapy who could
      offer training if time and resources permitted. CONCLUSIONS: Current training
      requirements are not being fulfilled. There are consultants and senior registrars
      who have psychotherapy qualifications to provide psychotherapy training but there
      are inadequate resources and time to formalise training. It is unlikely that the
      implementation of training requirements by the new college will be realisable
      without a review of training delivery.

PMID- 30199982
TI  - Suicide ideation, psychological adjustment and mental health service support: A
      screening study in an Irish secondary school sample.
AB  - OBJECTIVE: The aim of this exploratory study was to investigate the extent of
      suicide ideation, psychological maladjustment and views of mental health service
      support in a sample of secondary school pupils. METHOD: A cross-sectional survey
      was conducted on a purposive sample of participants (n=93) recruited from a
      secondary school located in the south east of Ireland. Participants completed a
      Background Information Questionnaire (BIQ); the Suicide Ideation Questionnaire
      (SIQ); and the Reynolds Adolescence Adjustment Screening Inventory (RAASI).
      RESULTS: Approximately ten percent of participants displayed high levels of
      suicide ideation whilst one third reported having previously had suicidal
      thoughts; one quarter reported psychological adjustment difficulties, although
      these varied by age and sex. Participants' drug use and their levels of parental
      closeness were both individual factors that significantly predicted both suicide
      ideation and psychological adjustment. Females reported higher levels of parental
      closeness than males. Forty percent of respondents rated mental health support
      services as insufficient to meet their needs. CONCLUSION: The findings raise
      serious concerns about the extent of suicidal thoughts amongst young people in
      Ireland; they also highlight a potentially important role for parents in this
      regard. Further research should ascertain national prevalence rates whilst
      appropriate school-based mental health education/promotion and support services
      should also be implemented.

PMID- 30199983
TI  - Graphology and psychiatric diagnosis: Is the writing on the wall?
AB  - OBJECTIVE: To review the role of handwriting analysis in psychiatry. METHOD: Case
      report and review of key papers. RESULTS: M, a 27-year-old man, presented with
      incoherent speech, palilalia, logoclonia, incongruous affect, paranoid delusions
      and auditory hallucinations. M was diagnosed with schizophrenia and cannabis
      misuse, complicated by speech and language difficulties. M spent long periods
      writing on pieces of paper; towards the start of his admission, his writing was
      unintelligible but became more intelligible as his psychosis resolved. M's
      handwriting demonstrates clinical features of psychosis (e.g. clang associations)
      and graphological abnormalities associated with schizophrenia in the literature
      (rigidity in letter-formation, mechanical expressions, and tendency toward over
      use of straight lines). CONCLUSION: Analysis of handwriting is likely to play a
      limited role in psychiatric diagnosis but may prove useful in monitoring clinical
      improvement in certain patients.

PMID- 30199984
TI  - Psychiatric power: A personal view.
AB  - One of the most important questions facing psychiatry today concerns its
      relationship to the emerging international service user movement. I believe that
      this movement presents not only the greatest challenge to psychiatry, but also
      the greatest opportunity. As it becomes more organised and influential this
      movement is starting to play a major role in shaping the sort of questions that
      are being asked about mental health services and their priorities. Yet there is
      limited reflection in our profession about how we, as doctors, might engage
      positively with it. It seems that while we are comfortable working with
      individuals and organisations who accept the medical framing of mental problems,
      we are less willing to contemplate working with critical service users. These are
      people who reject the medical model because they feel harmed by a system that
      describes their problems using the language of psychopathology. If we are serious
      about having an inclusive debate on mental health we will have to overcome this
      impasse. We need to entertain the idea that people who reject the medical framing
      of their problems are nevertheless legitimate stakeholders. It is time that we
      learned how to talk to them and to listen to their ideas. The user movement, with
      its substantial critical component, is not going to go away. One of the most
      important elements of the relationship between psychiatric services and the
      people who use them is the reality of psychiatric power. Many critical service
      users accept that legally sanctioned interventions may be necessary when
      individuals lose capacity to care for themselves and perhaps put themselves or
      others at risk. However they do not accept the fact that the Mental Health Act in
      Ireland gives sole authority to doctors to take decisions on such interventions
      without any obligation to consult other interested parties.

PMID- 30199985
TI  - Interaction of duloxetine with warfarin; a cautionary report.

PMID- 30199986
TI  - Psychiatric training and research in Ireland, the trainee's perspective.

PMID- 30199987
TI  - Anxiety and depression among opiate users who misuse substances during treatment.
AB  - OBJECTIVES: While treatment is known to improve drug and crime outcomes for
      opiate users, there is debate in the literature about the longitudinal effects of
      substance misuse and the comorbidity of mental health problems. We sought to
      describe and model anxiety and depression outcomes during opiate substance misuse
      treatment. METHODS: The first national, longitudinal treatment outcome study of
      404 opiate users entering a new episode of inpatient or outpatient treatment and
      followed up at one and three years and assessed using the Maudsley Addiction
      Profile instrument. RESULTS: A total of 404 opiate users were recruited
      representing approximately 8.2% of all new treatments and 17% of all new
      methadone treatments at national level in Ireland in 2003. At three years 97% (n
      = 392) were followed-up. At one year, analysis revealed the odds of experiencing
      depression was between five and 15 times the odds for opiate users who also used
      cocaine than non cocaine using opiate users, but this had decreased at three
      years. At three years those who were drug free, that is, not in treatment and not
      using illicit drugs, were less likely to experience feeling hopeless about the
      future than those in treatment or those not in treatment and using, but they were
      also more likely to experience feeling tense. Those in treatment were more likely
      to feel lonely. CONCLUSION: The concurrent misuse of cocaine and other substances
      during opiate treatment and the stage of the treatment pathway are associated
      with anxiety and depression among opiate users in treatment. These client factors
      need to be considered when implementing individualised treatment care plans.

PMID- 30199988
TI  - Developing a brief tool for anger assessment in clinical settings.
AB  - OBJECTIVES: To develop and validate a new brief assessment tool for anger in
      clinical settings at the Cluain Mhuire Acute Day Hospital. METHODS: The Cluain
      Mhuire Clinical Anger Scale (CMCAS) was developed using mixed methods including
      content analysis of interviews with five clients and six clinicians and
      qualitative item analysis of nine existing assessment tools. An initial 16-item
      scale was completed by 112 clients of a psychiatric day hospital and a
      nonclinical comparison group (n = 76). RESULTS: Psychometric analysis found that
      the CMCAS consisted of one 12-item factor with good internal reliability (alpha =
      0.82, n = 178) and good test-retest reliability (r = 0.93, n = 12) and converged
      with scores on STAXI-2. It distinguished between a sub-group referred for an
      anger management programme and matched groups from non-anger clinical and non
      clinical samples (F(2) = 18.13; p < .01). CONCLUSIONS: Findings suggest the CMCAS
      may be useful in clinical settings as a screening and assessment tool.

PMID- 30199989
TI  - Therapeutic alliance in forensic mental health: coercion, consent and recovery.
AB  - OBJECTIVE: We examined the Working Alliance Inventory (WAI) and Interpersonal
      Trust in Physician (ITP) in a forensic psychiatry hospital, where all patients
      were detained under mental health legislation for psychosis. We hypothesised that
      working alliance and trust are bilateral and can be measured. METHOD: We adapted
      the WAI and ITP minimally so that patients rated both their treating psychiatrist
      and primary nurse. We also adapted them minimally so that clinicians could rate
      WAI and ITP with the patient. A total of 81 of 83 patients completed the
      assessments. The clinicians (seven consultant psychiatrists and 43 nurses) also
      completed a minimally altered version of the same questionnaires. All three
      (patient, nurse and psychiatrist) were blind to the ratings of the others.
      RESULTS: Cronbach's alpha was greater than 0.9 for both patient and clinician
      versions of the WAI and greater than 0.8 for the ITP. The WAI and ITP correlated
      with each other (Spearman r > 0.67 for patients, for psychiatrists and for
      nurses). Patients rated clinicians higher than clinicians rated patients. Ratings
      were higher in pre-discharge wards than in acute wards. Patients' ratings of WAI
      for their psychiatrist and nurse correlated r = 0.75, and patients rating of IPT
      for psychiatrist and nurse correlated 0.67. Psychiatrists correlated with nurses
      0.38 for WAI, 0.53 for IPT. Psychiatrists and patients mutual ratings correlated
      r = 0.35 for WAI, 0.24 for IPT. Nurses and patients correlated r = 0.34 for WAI,
      0.25 for IPT. All correlations were statistically significant. Mental state
      (PANSS) and global function (GAF) correlated with all ratings and confounded most
      patient-clinician correlations. CONCLUSION: Working alliance and interpersonal
      trust can be measured reliably even in forensic settings. The extent to which
      they measure a mutual quality is unclear.

PMID- 30199990
TI  - Mephedrone and 'head/hemp' shop drugs: a clinical and biochemical 'heads up'.

PMID- 30199991
TI  - Users' experiences of cathinones sold in head shops and online.
AB  - OBJECTIVE: We describe use and effects of head shop powders among opiate
      dependant polydrug users and recreational drug users. These powders contain
      cathinones and were sold as bath salts or plant food via the internet or in head
      shops. METHOD: As this is a relatively new phenomenon, a qualitative approach
      using three data sources, in-depth interviews, a focus group (containing 10
      opiate users) and a head shop website containing 49 product reviews, was
      employed. Themes were identified. RESULTS: According to the study population,
      these powders mimic the effects of cocaine, ecstasy and amphetamines. These
      substances were snorted, ingested or injected by people and were not used as bath
      salts or plant food. The users' experience indicates that these powders have the
      potential for dependence, and exhibit side effects such as insomnia, anxiety and
      other mental health effects. The users report that the effects of the substances
      vary over time indicating that the chemical contents of the powders may change.
      CONCLUSION: Though users' descriptions of effects varied, there were indications
      of health and dependency effects which were more severe and more common among
      problematic opiate users, who also experienced increased social vulnerability. In
      general the recreational drug users considered their side effects to be mild and
      worth the drug induced experience.

PMID- 30199992
TI  - Two psychiatric presentations linked with 'head shop' products.
AB  - We report two cases of acute onset and rapid resolution of psychotic symptoms,
      the first following oral ingestion and the second following intravenous injection
      of some head shop products (HSPs). Both were associated with autonomic
      instability and negative results on urine toxicology screening using standard
      techniques. They highlight the potential dangers of managing such cases in acute
      stand-alone psychiatric units. Recent advance in characterising some HSPs by
      toxicology screening is also discussed.

PMID- 30199993
TI  - Whack induced psychosis: A case series.
AB  - 'Whack' is a new psychoactive substance available until recently in 'head shops'.
      It contains two active constituents, 4-fluorotropacocaine and desoxypipradrol. We
      present two case reports of subjects who developed acute psychotic states after
      using Whack. Both individuals displayed similar affective and anxiety symptoms in
      the presence of significant psychotic symptoms. Both required inpatient treatment
      but displayed a good treatment response to atypical antipsychotic agents. To our
      knowledge, this is the first published case series relating to this psychoactive
      substance.

PMID- 30199994
TI  - Benzylpiperazine-induced acute delirium in a patient with schizophrenia and an
      incidental temporal meningioma.
AB  - Benzylpiperazine is a psychotropic compound that has been widely available until
      recently from licensed premises such as 'head shops'. This report describes a
      case of a 48 year old man with schizophrenia who developed an acute delirium
      secondary to benzylpiperazine use, although he initially presented as a
      diagnostic conundrum. Investigation of his delirium unearthed a temporal
      meningioma which appears to be an incidental finding. This is the first
      documented case of delirium due to benzylpiperazine use. Benzylpiperazine has
      significant abuse potential and psychiatric complications. Its sale and
      possession have recently been made illegal in Ireland, which may limit its abuse
      in the future.

PMID- 30199995
TI  - Exhaustion, depression and hopelessness in cardiac patients: a unidimensional
      hierarchy of symptoms revealed by Mokken scaling.
AB  - OBJECTIVES: Depression and vital exhaustion are associated with poor
      cardiovascular prognosis, but there is substantial overlap between these
      constructs. Factor analytic studies have been inconclusive, and may not be the
      optimal analytic strategy to assess dimensionality. We assessed whether
      exhaustion and depression formed a single, hierarchical dimension using a form of
      nonparametric item response theory. METHODS: Patients with acute coronary
      syndrome (n = 430) completed questionnaires assessing depression and vital
      exhaustion. Mokken scaling was used to assess dimensionality. RESULTS: Mokken
      scaling formed a strong unidimensional scale, ordered in a hierarchy reflecting
      prevalence: fatigue (common), depression (less common) and hopelessness (rare).
      CONCLUSIONS: Depressive symptoms form a clear hierarchy in cardiac patients, from
      fatigue to hopelessness. Vital exhaustion may be considered a less severe form of
      depression. Use of hierarchical scales may allow clinicians to better determine
      clinical significance and target interventions.

PMID- 30199996
TI  - ECT: An investigation of lay attitudes and experiences in an Irish sample.
AB  - OBJECTIVES: Electroconvulsive therapy (ECT) is one of the most controversial
      psychiatric treatments of the modern era. Few studies have used validated scales
      to examine attitudes and knowledge regarding ECT in lay people. We examined
      attitudes, knowledge and experience of ECT using standardised questionnaires in
      Irish lay people, and compared the present results with the findings from a
      similar study reported over 25 years previously. METHODS: A total of 103 lay
      people were recruited from a variety of settings and completed a questionnaire.
      Data were analysed using independent samples t-tests, chi2 tests and Pearson
      correlations. RESULTS: Attitudes to ECT among Irish lay people are negative and
      knowledge of the treatment is poor. A significant correlation (r = 0.32) was
      found between knowledge and attitudes, with higher levels of knowledge associated
      with more positive attitudes. People with relatives who experienced ECT had a
      significantly higher ECT knowledge than the people without such relatives (p <
      0.05). CONCLUSION: Results confirmed previous findings and revealed novel
      statistically significant factors that contributed to attitudes towards ECT.
      Further replications are required to examine the findings' robustness and the
      relationship between attitudes, knowledge and experience. Such research can help
      increase the understanding of ECT and remove the stigmatisation associated with
      ECT. Mental health education programmes should consider the relation between
      knowledge and attitudes to better inform programme focus and content.

PMID- 30199998
TI  - John Dunne Medal.

PMID- 30199997
TI  - A study of consultant psychiatrists' response to patients' suicide.
AB  - OBJECTIVES: A patient's suicide is arguably the event of most concern to
      consultant psychiatrists. Given the rise in the rate of suicide in the Republic
      of Ireland, the impact it has should not be underestimated. The aims of the study
      were: to assess the effect a patient's suicide has on a consultant's personal and
      professional life; to identify what factors modulated or exacerbated their
      response to the suicide; and to highlight what was shown to be beneficial in
      coping with the aftermath. METHODS: Following a literature review, a
      questionnaire from a previous study was chosen. This was sent to 74 consultants
      working in the Munster province. It asked consultants to recall their 'most
      distressing' suicide and their response to it. The results were analysed using
      quantitative methodology. A further literature review was conducted on the issues
      raised. RESULTS: The questionnaire response rate was 67.5%. A total of 80% of
      consultants had a patient commit suicide under their care. In the case of 27.5%,
      consultants said that their personal lives had been affected by the suicide and
      32.5% said that their professional lives had been affected. The majority of those
      affected were recently appointed consultants. Consultants' peers and team were
      significant sources of support, as were team meetings. A total of 57.5% of
      consultants said that their management of future suicidal patients had changed
      following the suicide. CONCLUSIONS: A proportion of consultants experience
      negative effects in their lives as a consequence of patient suicide. However the
      support of consultant peers, the team and team meetings may help in the
      aftermath.

PMID- 30199999
TI  - Tardive dysphoria: antidepressant-induced chronic depression.
AB  - OBJECTIVES: A significant number of depressed individuals experience inadequate
      benefit from long-term antidepressant use. This paper investigates the hypothesis
      that in some individuals persistent use of antidepressants may be prodepressant.
      METHODS: Literature regarding the effect of long-term use of antidepressants was
      reviewed by searching PubMed and Ovid data bases with terms: antidepressant
      tachyphylaxis, treatment-resistant depression, chronic depression and
      antidepressant tolerance. RESULTS: Antidepressant treatment-resistant patients
      frequently had a positive initial response to antidepressants. When resistance
      appeared, initial increases in dose or medication changes usually resulted in
      transient improvement. Eventually, the episodic course of the original depressive
      illness was replaced with a continuous, unresponsive depressive syndrome. We
      propose the term tardive dysphoria to describe this phenomenon. CONCLUSIONS: The
      phenomenon of antidepressantinduced depression, or tardive dysphoria, needs to be
      experimentally examined in blinded, randomised antidepressant discontinuation
      studies.

PMID- 30200001
TI  - ECT - Irish national studies.

PMID- 30200000
TI  - Caffeine and clinical change in a patient with schizophrenia on a long-stay ward.
AB  - We report a case of a 33-year-old male patient with schizophrenia, who showed
      significant and persistent changes in psychotic and mood symptoms relating to his
      caffeine intake.

PMID- 30200002
TI  - Tobacco smoking and mental illness: important considerations.
AB  - Tobacco smoking is a contributory factor in the death of 50% of individuals who
      are regular or heavy smokers (The Office of Tobacco Control Ireland defines a
      regular smoker as someone who smokes 11-20 per day and a heavy smoker as someone
      who smokes 21 or more cigarettes per day). The World Health Organisation (WHO)
      regards tobacco smoking as the leading preventable cause of death worldwide. In
      Ireland, approximately 750,000 people smoke tobacco regularly (23.5% of the
      population) with 7,000 Irish people dying annually from smoking-related causes.
      Although there are no exact figures for prevalence rates of smoking in
      individuals with mental illness in Ireland, international studies unequivocally
      state that the prevalence of smoking is significantly higher in those with mental
      illness, with greater nicotine intake and increased prevalence of nicotine
      dependence also reported. Furthermore people with mental illness experience
      greater withdrawal symptoms and have lower cessation rates when attempting to
      stop smoking compared to the general population.

PMID- 30200003
TI  - Deinstitutionalisation - time to move on to legislation?

PMID- 30200004
TI  - Meeting standards set for non self-harm presentations to emergency departments.
AB  - OBJECTIVES: The commonest psychiatric presentation in most emergency departments
      (EDs) is deliberate self-harm. However, there are other significant categories of
      psychiatric presentation which include alcohol and substance misuse, acute
      psychosis and mood disorder. In addition to the NICE Guidelines for deliberate
      self-harm, there are good practice guidelines available for the management of
      other psychiatric attendances to the ED. The aim of this study was to identify
      the psychiatric attendances other than deliberate self-harm to Beaumont Hospital
      ED over a 12-month period with the objective of studying the rates and
      characteristics of attendances and to investigate whether good practice
      guidelines were met. METHOD: From a total of 657 psychiatric attendances other
      than deliberate self-harm which were recorded, data was collected on
      demographics, provision of a psychosocial assessment and adherence to good
      practice guidelines. RESULTS: Alcohol (38%) was the most common reason for
      presentation. Of the total number of attendees, only 44% received a psychosocial
      assessment compared to 59% of attendees who had presented following deliberate
      self-harm during the same 12-month period. CONCLUSIONS: The attendees who did not
      receive a psychosocial assessment represent a vulnerable group in which the
      levels of psychosocial assessment need to be improved in order to meet good
      practice guidelines standards of care.

PMID- 30200005
TI  - Deliberate self-harm in children and adolescents: an 11-year case note study.
AB  - OBJECTIVE: To retrospectively examine the case-notes of all children and
      adolescents admitted with deliberate self-harm (DSH) or suicidal ideation during
      the study period 1993-2003. The study aimed to identify underlying reasons why
      children and adolescents engage in DSH, and to identify common psychiatric,
      psychosocial and familial factors which may predispose or contribute to an
      individual's engagement in such behaviour. METHOD: All children presenting to the
      hospital with DSH or suicidal ideation were identified and data collected from
      their case notes. A study specific questionnaire was designed to collect
      demographic details, details on clinical presentation, past attempts, comorbid
      psychiatry disorders, family history and family circumstances. Information was
      also recorded on hospital stay and discharge planning. RESULTS: During the 11
      year period, 231 children presented with suicidal ideation or behaviour. The mean
      age was 12.85 with an age range from 6-17 years, with a female:male ratio of
      2.5:1. Overdose was the most common method (81.2%) and paracetamol most commonly
      the drug of choice. More than half of the group (55.7%) expressed a wish to die.
      More than half (51.8%) had expressed suicidal ideation in the past, 31% had made
      a previous attempt, and 11.7% had been previously admitted. Of the children 8%
      presented with suicidal behaviour more than once over the study period. There was
      a family history of completed suicide in 6.6%. CONCLUSION: Deliberate self-harm
      in young people is a significant public health problem in Ireland. During the
      period of this study, rates have continued to increase. There is an urgent need
      for national bodies such as the National Suicide Review Group to extend their
      focus to include those under age 18 and for services to be developed that might
      reduce DSH behaviours. More research is needed in the area of childhood suicidal
      behaviour.

PMID- 30200006
TI  - Attitudes of consultants to prescribing ECT for patients involuntarily admitted
      under MHA 2001.
AB  - OBJECTIVES: The Mental Health Act (MHA) 2001 provides the legislative structure
      in Ireland for the involuntary admission and treatment, including with ECT, of
      patients suffering from mental disorders. A recent Seanad Bill proposed removing
      the option of administering ECT to involuntary patients who do not provide
      informed consent. This controversial issue has stimulated extensive media and
      stakeholder debate. In this study we explored the attitudes of consultant
      psychiatrists towards prescribing ECT for involuntary patients. METHODS: We
      compiled a current list of consultant psychiatrists attached to approved centres
      nationwide. We sent a study specific questionnaire to consultants of all adult
      psychiatry specialties. RESULTS: From the 249 individualised anonymous
      questionnaires posted, 164 (66%) were returned and analysed. When clinically
      indicated for involuntary patients willing to consent to ECT treatment, 159 (97%)
      consultants stated that they would and three (2%) would not prescribe ECT. For
      involuntary patients who lack capacity and are unable to consent, 157 (96%)
      consultant psychiatrists stated that they would and six (4%) that they would not
      prescribe ECT. For involuntary patients who have capacity to consent but are
      unwilling to do so, 52 (32%) consultant psychiatrists stated they would and 104
      (63%) would not prescribe ECT. CONCLUSIONS: The overwhelming majority of
      consultant psychiatrists would prescribe ECT for involuntary patients who are
      unable to consent to this treatment. Divergent attitudes emerged for treating
      patients who are unwilling to consent, with most consultant psychiatrists stating
      they would not prescribe ECT for this patient group.

PMID- 30200007
TI  - Prevalence of substance misuse comorbidity in an Irish university training
      hospital.
AB  - OBJECTIVE: Substance misuse complicates an individual's management in adult
      Mental Health services. This study aimed to examine both the overall prevalence
      of substance misuse in those admitted to the psychiatric unit and additionally
      those admitted with a primary diagnosis and comorbid substance misuse. The study
      focuses on the associated diagnoses and demographics in 100 consecutive
      admissions to an acute psychiatric unit in an Irish university hospital. METHOD:
      Clinical notes were reviewed independently by two members (one being a doctor),
      of the multi-professional research team within four days of their admission.
      Substance misuse proximal to the/at the time of admission (reflecting the current
      usage) was noted. RESULTS: The combined prevalence of mental illness and
      substance misuse was 47% (CI 37-57%). Twenty two out of 100 (22%, CI 14-32%) were
      admitted primarily for the management of substance misuse and dependence (plus
      psychosocial reasons). Twenty-five of the patients admitted with a primary
      psychiatric illness (25%, CI 17-31%) were discovered to have comorbid substance
      misuse. At risk groups were found to be males and aged under 45 years.
      CONCLUSION: Our study demonstrates the importance of screening and identification
      for substance misuse in psychiatric inpatient units; and consequently, the need
      for individual case management, additional development of dual diagnosis services
      and accurate patient data reporting to facilitate forward service-planning.

PMID- 30200008
TI  - Prevalence of obesity and metabolic syndrome in a long-stay psychiatric unit.
AB  - OBJECTIVE: The aim of this study was to determine the prevalence of metabolic
      syndrome and obesity as defined by Body Mass Index (BMI) in a long-stay
      psychiatric unit where all care is provided by the psychiatric team. METHOD: All
      residents in this long-stay unit were screened. Their BMI was calculated. Waist
      circumference and blood investigations were done. Ward records were used to
      determine those who had been previously diagnosed with hypertension and diabetes.
      The ATP 111 criteria were used to determine the prevalence of metabolic syndrome.
      RESULTS: We found a prevalence of 33% for BMI obesity and a prevalence of 66% for
      metabolic syndrome. These are higher than those of the general Irish middle aged
      population and the accepted estimate of a general psychiatric population. It is
      also higher than that of a previous published study on an Irish long-stay
      psychiatric ward population. CONCLUSION: There is high prevalence of BMI obesity
      and metabolic syndrome in long-stay psychiatric residents. This has the potential
      to impact significantly on physical morbidity and mortality. People with severe
      and enduring mental illness should have access to primary care and other health
      services on the same basis as any other citizen.

PMID- 30200009
TI  - The physical health of residents of long-stay wards in Carlow/Kilkenny.
AB  - OBJECTIVES: This audit is supported by regulations within the Mental Health Act
      2001. It is in response to the Mental Health Commission Strategic Priority Number
      One, Quality Framework, 2002-2008 which aims to promote high standards of
      physical examination in the care of long-stay residents of psychiatric
      facilities. It is based on improved awareness of adverse effects of mental
      illness or its treatment on physical health. This awareness informs better
      practice. METHOD: Physical examination proforma and case notes of all long-stay
      residents in wards in Carlow and Kilkenny were assessed over a six month period
      to examine the quality of physical examination. Following departmental meetings
      and literature review, standards of care as recommended by the Royal College of
      Psychiatrists in Occasional Paper 67 and Irish statutory documents were agreed to
      be the appropriate benchmark. RESULTS: Areas of strength were the examination of
      'routine' systems (> 92%), ie. cardiovascular, respiratory, alimentary, central
      nervous, genitourinary and the frequency of clinical review by treating
      psychiatric team. Areas needing improvement were eye (8%) and ear (3%)
      examinations, measurements of weight (58%), height (1.6%), body mass index
      (1.6%), waist circumference (0%), investigating for prostatic specific antigen
      (50%), discussion of results of physical examination and investigations with the
      residents (both 0%) and referral to BreastCheck (36%). CONCLUSION: A new physical
      examination form has been created for long-stay residents to correct these
      deficiencies and a new departmental policy document setting out a standard of
      practice consistent with recommended practice and general statutory requirements
      has been put into place.

PMID- 30200010
TI  - Audit of documentation of allergies in a psychiatric inpatient unit.
AB  - OBJECTIVES: This audit aimed to: identify the level of allergy documentation in
      admission notes, case notes and medication charts in the Department of
      Psychiatry, Portlaoise; establish the degree of compliance to the gold standard
      guidelines; highlight areas requiring further improvement and make realistic
      recommendations to ensure better compliance with the stipulated guidelines on
      allergy documentation; and re-audit after six months. METHODS: Gold standard
      guidelines on allergy documentation were obtained from various sources. Audit was
      performed over three days during which data was collected from the allergy
      section of medication charts, current case notes and original admission notes in
      both acute and long-stay wards. Recommendations were made and some were adopted,
      changes to practice were implemented for six months; at which time re-audit was
      performed. RESULTS: The initial audit revealed that: the allergy section was
      completed in 25% of medication charts; only 12% of current case notes had any
      documentation of allergy status; an for the original admission notes, the allergy
      section was documented in 65% of notes. Based on these results, a formal initial
      assessment proforma with a designated allergy section was introduced and a
      renewed awareness of the importance of the documentation of allergy status was
      actively promoted amongst non consultant hospital doctors (NCHDs). Six months
      later, re-audit showed that: in the medication charts there was a significant
      improvement in the level of compliance with documentation of allergy status
      (allergy or NKDA) in the allergy section up from 25% to 58.1%; in the current
      case notes, there was only marginal improvement in the level of compliance on the
      front of case notes from 12-19.1%; and in the original admission notes, there was
      also considerable improvement in the level of compliance with documentation of
      allergy status up from 65% to 80.9%. CONCLUSION: This audit improved the level of
      documentation of allergy sections in the relevant areas and therefore helped in
      preventing avoidable and potentially fatal allergic reactions. It will also help
      save money for the Health Service Executive by reducing compensation costs filed
      by patients.

PMID- 30200011
TI  - Cognitive remediation therapy for schizophrenia: what is it and does it work?
AB  - Impaired cognition is a core feature of schizophrenia (SZ) that precedes,
      accompanies, and often outlasts a patient's clinical symptoms. The success of new
      generation antipsychotics, as well as their failure to ameliorate the persistent
      disabilities associated with the disorder are well documented. Consequently, a
      number of psychosocial and cognitive interventions have been developed to address
      specific aspects of disability not adequately alleviated by medication. Among
      these, interventions adapted from the acquired brain literature that target
      cognitively based disability (cognitive remediation therapy; CRT) have received
      significant empirical support both for ameliorating specific deficits in memory,
      attention and executive function, and improving real world outcome. CRT
      strategies have focused either on providing drill-based training aimed at
      increasing capacity or providing behavioural strategies for compensating for
      cognitive deficits, or a mixture of both. Nonetheless, these interventions have
      varied widely and several questions remain. This review provides a brief overview
      of cognitive remediation therapies in psychosis, discusses evidence for its
      success, and outlines a number of questions that remain about its implementation.
      Given the current unavailability of cognitive remediation as part of standard
      care in Irish mental health services, we conclude by describing one such
      intervention developed within our clinical research group and the questions we
      hope to address in making this programme more widely available to Irish patients.

PMID- 30200012
TI  - Hydrocephalus and bipolar affective disorder.
AB  - Bipolar disorder can emerge in the context of organic brain pathology. In the
      case presented, long-standing hydrocephalus was diagnosed in a man with
      relatively late-onset bipolar illness who presented initially with somewhat
      atypical, treatment-resistant depressive symptoms. Hypomania, followed by a rapid
      cycling bipolar course, subsequently developed. This report reviews the
      association between bipolar disorder and hydrocephalus, and examines possible
      neurobiological mechanisms implicated in both conditions.

PMID- 30200013
TI  - Diogenes syndrome and autistic spectrum disorder.
AB  - Diogenes syndrome or senile squalor syndrome has been described in the
      psychiatric literature with an associated mental illness in between one half and
      two thirds of the cases cited. The occurrence of the syndrome in the absence of a
      psychiatric disorder has received much attention with many hypotheses proposed.
      We present the case of a 72-year-old man living for many years in domestic
      squalor whose presentation, neuropsychological profile and history suggest an
      underlying autistic spectrum disorder. We are not aware of any similar case in an
      older adult reported in the medical literature. The co-occurrence of these two
      conditions is an intriguing one as certain key features of autistic spectrum
      disorder may predispose to Diogenes syndrome.

PMID- 30200014
TI  - Long-term prospective mood self-rating and antidepressant treatment.
AB  - The use of antidepressants in bipolar illness remains controversial. This
      controversy continues to be fuelled by short-term studies that inconsistently
      report efficacy or no benefit. However, long-term studies have been consistently
      unfavourable, suggesting that understanding the long-term course of the illness
      in the setting of antidepressant treatment is important. This is an extraordinary
      case in which prospectively collected daily mood ratings were available in a type
      I bipolar individual who had experienced minimal medication changes over a 21
      year period was reviewed. Data regarding the number of euthymic days in the
      setting of antidepressant use and after antidepressant discontinuation were
      collected. Induction of cycling and increase in the number of depressed days
      occurred after five years of continuous serotonergic antidepressant
      administration. Discontinuation of antidepressants after 11 years of continuous
      use was associated with only a partial improvement which had a delayed onset.
      Cycling and increase in depression was noted after years of continuous use of
      serotonergic antidepressant treatment. Antidepressant-associated destabilisation
      may occur after long-term exposure and may be associated with prolonged worsening
      even after antidepressant discontinuation.

PMID- 30200015
TI  - First episode psychosis and an underlying cerebellar tumour.
AB  - We report on the case of a middle aged lady who was referred by her GP with what
      appeared to be a case of first episode psychosis. Following assessment and
      investigation an underlying cerebellar tumour was identified. Our aim is to draw
      attention to the ongoing debates regarding the possible role of the cerebellum in
      psychosis and cognition and on neuroimaging as a diagnostic modality in cases of
      first episode psychosis.

PMID- 30200016
TI  - Antidepressant augmentation and combination in unipolar depression: strong
      guidance, weak foundations.
AB  - Depression will be the second leading contributor to the global burden of disease
      by 2020. In Ireland, in 2009, 6061 people were hospitalised with depressive
      disorders. This represents a significant economic and social burden. There is
      growing awareness of the difficulty in treating depression with medications
      alone. The likelihood that a patient will achieve remission with the first
      antidepressant tried is around 30%, and the rates are similar for the second
      antidepressant tried. This falls to around 15% after three trials. Many patients
      are exposed to pharmacotherapy for extended periods of time with little
      beneficial effect, but often with side-effects. Patients are therefore in great
      need of clear information with regard to their chance of success. Clinicians are
      in need of clear guidance on prescribing strategies which have proven efficacy.
      However, this guidance often discusses treatment strategies based on varying
      levels of evidence. Guiding bodies may approach the problem from varying
      perspectives. The UK National Institute for Health and Clinical Excellence (NICE)
      has a clear government mandate with regard to provision of not only effective but
      cost-effective treatments. The British Association of Psychopharmacology (BAP) is
      an independent body of interested researchers and therefore may discuss
      prescribing options from the point of view of tertiary care institutions, and
      university centres. The South London and Maudsley NHS Foundation Trust publish
      the popular Maudsley guidelines. These are perhaps more pragmatic in nature, but
      include very low levels of evidence, including case series. The American
      Psychiatric Association (APA) is an independent member association which also
      publishes guidelines. These are published in the American Journal of Psychiatry
      and the latest guidelines were published in October 2010. All these bodies
      attempt to weigh their advice according to the level of evidence available and
      aim to provide clinical guidance in difficult situations. The burden on guiding
      organisations is to provide some direction and clarity in areas that are often
      unclear or controversial. Clinical guidelines are one method of providing support
      and guidance to busy clinicians. However, this clinician-centered approach has
      limitations. The onus is on the authors of the guidance to provide ever-more
      treatment options. This may mean that conclusions about the efficacy of
      medications is overstated or the limitations of the literature not fully explored
      in explanatory notes.

PMID- 30200017
TI  - Dementia care in Ireland: what's the plan?

PMID- 30200018
TI  - Plus: An appreciation: In memory of Prof Eadbhard O'Callaghan.

PMID- 30200019
TI  - Who attends outpatient adolescent mental health services?
AB  - OBJECTIVES: This study set out to profile the diagnoses and level of suicidal
      behaviour of adolescents aged 12-15 years newly referred to a Child and
      Adolescent Mental Health Service (CAMHS). Information on the nature and range of
      disorders and level of functional impairment among adolescents attending
      outpatient CAMHS is important for service planning and development. METHODS: A
      total of 100 newly referred adolescents were assessed using the KSADS-PL
      standardised interview. Overall level of functional impairment was measured using
      The Clinical Global Impressions Scale and The Children's Global Assessment Scale.
      RESULTS: Results showed that the majority of adolescents had more than one
      disorder, with almost one quarter having four or more disorders. Behavioural
      disorders were the most common diagnostic category, followed by anxiety
      disorders, and affective disorders. Although relatively uncommon, levels of
      functional impairment were highest in those with psychotic disorders, followed by
      substance abuse disorders. The most common pattern of comorbid disorders were
      depressive disorders plus anxiety disorders, followed by anxiety disorders plus
      behavioural disorders and depressive disorders plus behavioural disorders. One
      quarter of the young people had engaged in suicidal acts in the six months prior
      to attendance, while this had been the case in over one half of those with a
      depressive disorder. CONCLUSION: This study showed that adolescents attending
      CAMHS tend to have multiple disorders, high levels of suicidality, and are
      significantly functionally impaired. These factors need to be taken into account
      in the development of effective treatments.

PMID- 30200020
TI  - Counter-urbanisation during Ireland's 'Celtic Tiger' period - mental health
      implications.
AB  - OBJECTIVES: This study (a) describes the clinical and demographic profile of
      urban to rural migrants attending a psychiatric outpatient clinic and (b)
      explores the impact of the move on patients' mental health and lifestyle.
      METHODS: A self-rated questionnaire distributed to 207 consecutive outpatients
      requested demographic and clinical information from migrant and non-migrant
      patients. A focus group study among a purposeful sample of 10 migrant patients
      explored participants perceptions of the move and its impact on mental health.
      RESULTS: One hundred and one patients (48.8%) returned the questionnaire. Most
      migrant responders described housing affordability as influencing their decision
      and were generally satisfied with the move. However, half reported reduced access
      to social amenities. Over half of the migrant outpatients had a previous
      psychiatric history and were mostly unemployed despite being home-owners.
      Predominant focus group themes included the perceived need to leave the city for
      the relative safety and calm of rural living as well as post-migration concerns
      regarding future isolation and diminished levels of support. CONCLUSION:
      Clinicians and service providers in rural areas should be informed by an
      awareness of the potential mental health implications of counter-urbanisation.

PMID- 30200021
TI  - Sharing control: user involvement in general practice based methadone
      maintenance.
AB  - OBJECTIVES: This study assessed patients' views of a methadone programme in a
      Dublin general practice including the degree to which the patients were 'involved
      in decisions about their treatment'. METHOD: All patients receiving methadone
      were asked to participate. A face to face questionnaire, with open and closed
      questions, was administered. Interviews lasted approximately 30 minutes.
      Quantitative data were analysed using descriptive statistics and qualitative data
      were analysed using a thematic approach. RESULTS: Forty one (87%) of the 47
      patients attending the general practice methadone service were interviewed. Of
      the 39 patients who had used heroin on admission, 69% had stopped and 31% reduced
      heroin use since starting methadone treatment. A total of 71% reported that the
      doctor either always involved (59%) or sometimes involved (12%) them in decisions
      about their treatment. Involvement was interpreted as 'being listened to' or
      'having a say' in deciding methadone dose. Surprisingly those who reported that
      they were not involved in treatment decisions were more likely to have stopped
      heroin use (10/11). A significant majority of patients (81%) expressed the desire
      to stop taking methadone. CONCLUSION: Most patients receiving methadone in
      general practice were listened to and had a say in deciding their methadone dose
      but did not have an opportunity to engage in more structured or contractual forms
      of involvement in treatment such as written care plans. In line with a patient
      centred approach, treatment providers should set their sights beyond the safe
      delivery of methadone, to provide a service which is centred on patient goals,
      expectations and choice.

PMID- 30200022
TI  - Communication between community mental health services and primary care.
AB  - OBJECTIVES: This study aims to assess the rate of six monthly communications
      between specialised psychiatric services and primary care and to determine
      factors which predict such communication. METHODS: A retrospective review of the
      clinical records of all patients attending the relevant local psychiatric
      outpatient clinic was carried out by all members of the multidisciplinary team to
      identify patient demographic and clinical variables as well as to determine if
      there has been documentation of communication with primary care in the preceding
      six months. Letters were sent to the relevant primary care teams regarding
      progress on their patients in cases where it was identified that no communication
      had occurred in the preceding six months. RESULTS: A total of 145 patients'
      charts were reviewed. Of these, 53.3% of the patients were females and 46.7% were
      males. The mean age was 47.9 years (SD = 14). Patients' diagnoses included;
      depression (41%), bipolar affective disorder (6.7%),
      schizophrenia/schizoaffective disorder (27.6%), anxiety disorders (6.7%), alcohol
      dependency syndrome (11%) and other disorders (7%). Overall, only 36% of
      patients' charts had a record of communication with primary care in the last six
      months. Only one variable, 'changes made to the patents medication in the last
      six months' was significantly associated with the likelihood that there had been
      communication with primary care with an odds ratio of 15 and a p-value of 0.00.
      CONCLUSION: A six monthly review has a potential to improve the level of
      communication between specialised psychiatric services and primary care.

PMID- 30200023
TI  - Multidisciplinary review to identify patients who could be managed in primary
      care.
AB  - OBJECTIVES: Primary care teams have the potential to deliver much of the care
      currently provided by specialist services. The aim of this review was to
      determine from patients' clinical records and multidisciplinary team discussions,
      those that may be suitable for discharge back into primary care. METHODS: A
      retrospective review of the clinical notes of all patients attending a
      psychiatric outpatient clinic was carried out by all members of the
      multidisciplinary team to determine the appropriateness of continuing to provide
      psychiatric services in a specialised psychiatric clinic rather than in a primary
      care setting, taking into account the patients demographic and clinical
      variables. RESULTS: It was recommended that 60% of all the patients needed to
      continue attending the local mental health service, 35.2% could be discharged
      back into primary care for continuing management whilst the remaining 4.8% could
      be managed jointly between primary care and the community mental health service.
      The bulk of the patients recommended for discharge into primary care had a
      diagnosis of anxiety disorder or depression and all of them had been stable on
      their treatment for more than six months. CONCLUSION: Regular multidisciplinary
      team review has a potential to identify patients who could be discharged back
      into primary care.

PMID- 30200024
TI  - Sociodemographic profile and mental health needs of referrals to an Irish
      psychiatric service: a transcultural perspective.
AB  - OBJECTIVES: This study describes the social, demographic and clinical
      characteristics of all the new referrals in a mental health catchment area. This
      study aims to compare Irish and non-Irish service users in terms of their mental
      health needs and service utilization. METHOD: Case notes were reviewed
      retrospectively to investigate demographic, clinical and service utilization
      parameters among new referrals to the psychiatric services in Galway, Ireland
      over a six-month period. RESULTS: One hundred and fifty-four new referrals, of
      whom 41 were non-Irish, presented over a six-month period. Results showed no
      difference between Irish and non-Irish service users in terms of socio
      demographic variables. Alcohol problems and subsequent need for detoxification
      and counselling were significantly higher among service users from the new EU
      accession states with a significant impact on the duration of their hospital stay
      and the need for intensive psychiatric care. CONCLUSIONS: There is an urgent need
      for enhanced resources for the delivery of mental healthcare to immigrants.
      Service utilisation and mental health needs are not explained merely by illness
      related aspects in immigrant service users. Social and cultural factors have to
      be recognised in order to prevent disadvantages in psychiatric care.

PMID- 30200025
TI  - Efficacy of a cognitive stimulation therapy programme for people with dementia.
AB  - OBJECTIVES: Cognitive stimulation therapy (CST) has been shown to produce
      improvements in cognition and quality of life which compare favourably with
      trials of cholinesterase inhibitors. The aim of the present study was to evaluate
      the efficacy of CST, replicating the methods of Spector et al in the British
      Journal of Psychiatry in 2003 in a smaller sample using a control group engaged
      in routine activities. METHODS: Eligible participants (mild to moderate dementia;
      MMSE range 10-23) were randomised to CST group or control conditions. Pre- and
      post-intervention testing was undertaken by assessors who were blind to
      condition. Measures included MMSE, CDR (sum of boxes), ADAS-cog, RAID (anxiety),
      abbreviated GDS (depression), QoL-AD, and the CAPE Behaviour Rating Scale (BRS).
      Analysis was by non-parametric statistics. Occupational therapists facilitated
      two sessions per week for seven weeks in two long-term care facilities and the
      same programme was run by the activity co-ordinator in a nursing home unit.
      RESULTS: Fourteen CST and 13 control participants completed the study. Between
      group difference scores analysis showed that the CST group improved compared to
      controls on MMSE (Mann-Whitney U = 32, p = 0.013) and on the QoL-AD which just
      fell short of significant (U=51.5, p = 0.055). Qualitatively, therapists noted
      that CST participants demonstrated good interaction and enthusiasm in the group
      environment, with continuity and carryover between sessions. CONCLUSIONS: Even
      though the sample sizes are small the current study is consistent with the
      Spector et al's findings in 2003 of beneficial effects in people with dementia
      following CST. The programme is recommended as an intervention for people with
      mild to moderate dementia.

PMID- 30200026
TI  - Lithium and prevention of cognitive impairment.
AB  - OBJECTIVE: To examine the rate of cognitive decline and occurrence of dementia
      among patients attending a lithium clinic for those aged 65 years and over.
      METHOD: Retrospective chart review of the cognitive function of 29 patients
      receiving maintenance lithium treatment attending the Dublin South East Old Age
      Psychiatry service, over a nine-year time period. RESULTS: Twenty-nine patients
      were included in the study (20 female, nine males), with a mean age of 79 years.
      Two patients had concurrent dementia. Six patients fulfilled ICD10 criteria for
      mild cognitive disorder and all of these patients also fulfilled revised
      consensus criteria for mild cognitive impairment amnestic subtype. Sixteen
      patients were commenced on lithium as an augmentation treatment for recurrent
      depressive disorder, 12 patients were on treatment for bipolar affective disorder
      and one patient on treatment for schizoaffective disorder. Patients had been
      receiving lithium treatment for an average of 109 months with follow-up by the
      service for a mean duration of 38 months. The initial mean MMSE score of patients
      at first presentation to the service was 26.9 (SD = 5.6) compared to a mean MMSE
      score 25.8 (SD = 5.8) (CI of change in MMSE score at 95% level = -2.1 and 0) at
      follow-up. The mean MMSE of patients with mild cognitive impairment prior at
      first contact with the service was 26.8 (SD = 3.2) and at follow-up was 26 (SD =
      3.2) which was not statistically significantly different (p=0.40) (CI for change
      in MMSE at 95% level = -3.2 to 1.5). No patient had developed incident dementia
      during the follow-up period of the study. CONCLUSION: The results tentatively
      suggest that lithium may have a protective effect against cognitive decline and a
      neuroprotective role in patients with concurrent affective disorder and cognitive
      impairment. Multi-centre prospective studies of cognitive function in patients
      attending lithium clinics are needed to examine the neuroprotective properties of
      lithium.

PMID- 30200027
TI  - Two-year study of the use of neuroimaging in a psychiatric inpatients unit.
AB  - OBJECTIVES: Neuroimaging is being used increasingly in the investigation of
      psychiatric disorders. Previous studies have found abnormalities in about two
      thirds of all scans done in psychiatry. The aim of our study was to investigate
      the use of CT and MRI in the management of inpatients in psychiatry department
      Adelaide & Meath hospital, Tallaght and to examine the relationship between
      diagnosis and abnormalities seen on scans. METHOD: We did a two-year
      retrospective study of all inpatient referrals for CT scans/MRI scans. A case
      note review of bio-demographic data, diagnosis, relevant medical history,
      substance misuse history, indication for tests and results of scans was done. We
      found that 66 CTs and MRI scans were done over the study period. RESULTS:
      Fourteen (21%) of the scans had abnormal results which were mostly atrophic
      changes. Of the 14 abnormal scans, seven had abnormal findings on neurological
      examination. We found a lower number of abnormal scans compared to previous
      studies. CONCLUSIONS: Radiological abnormalities were not disease specific. We
      wish to propose guidelines on the indications for using neuroimaging in
      psychiatric patients.

PMID- 30200028
TI  - Recovery from mental illness: changing the focus of mental health services.
AB  - The concept of recovery entered the lexicon of the mental health services in the
      1980s following the publication of a series of studies and personal narratives
      which demonstrated that the course of mental illness was not always one of
      inevitable deterioration and that people diagnosed with severe mental illness
      could reclaim or recover meaningful lives. For a long time, recovery was not
      thought possible by many family members, service providers and researchers.
      However globally, specific policy and clinical strategies are being developed to
      implement recovery principles although key questions remain. In fact, the
      possibility of recovery is still debated by some. In this paper, we include
      information about the recovery model and the medical model; we provide evidence
      for recovery and document changes in mental health practices and policies
      incorporating recovery as the guiding principle. We also attempt to address the
      debate as to whether recovery is an evidence based practice. We propose that
      evidence based practice should be complementary to value-based and narrative
      based practices and we suggest an integrative model that maximises the virtues
      and minimises the weaknesses of each practices (see Figure 1).

PMID- 30200029
TI  - Sexual dysfunction and antidepressants: a review with emphasis on treatment.
AB  - Sexual dysfunction (SD) is widely recognised as a potential side-effect of
      antidepressant therapy. SD has been reported with all classes of antidepressants
      (MAOIs, TCAs, SSRIs, SNRIs and newer antidepressants) in patients with depression
      and anxiety disorders. Increased attention has been directed at the SD produced
      by antidepressants; not only because its initial prevalence was underestimated
      but also because of the adverse impact that these side-effects can have on
      treatment compliance. Although SD is an important adverse effect of
      antidepressant medication, patients tend to be reluctant to report them if not
      directly questioned. This suggests that consideration of the doctor-patient
      relationship is needed when deciding on an appropriate treatment plan.

PMID- 30200030
TI  - Hypogonadism in an opioid dependent man.
AB  - We describe here the case of a 45-year-old man with a chronic history of heroin
      abuse who has received methadone maintenance therapy for 12 years. At admission,
      on this occasion, for stabilisation on methadone, he reported a two-year history
      of painful gynaecomastia and testicular atrophy. Investigations revealed abnormal
      sex hormone levels. Liver function tests, thyroid function tests, Brain
      (pituitary) MRI and viral screens were normal. Following assessment and
      abnormality in two morning total testosterone level measurements he was diagnosed
      with hypogonadism secondary to opioid use. Although he had a previous history of
      alcohol abuse, he was abstinent from alcohol use for five years at time of
      assessment. He was commenced on parenteral testosterone replacement with
      therapeutic benefit. In light of the increased use of opioids, it is important to
      recognise and manage the endocrine complications of opioid use. The need for an
      empathic and adequate sexual history, physical examination and investigation is
      essential in patients who use opioids to ensure that cases of hormonal
      dysfunction are detected early and managed appropriately.

PMID- 30200031
TI  - Relapse of postictal psychosis following 14-year symptom-free period.
AB  - Neuropsychiatric sequelae in patients with epilepsy have been vastly studied and
      documented. These may be affective, cognitive or psychotic. Certain risk factors
      may predispose some epileptics more to these sequelae. In general, good epileptic
      control may minimize these outcomes. We present in this report, a case of
      postictal psychosis (PIP), superimposed on delirium, in a 68-year-old woman, with
      history of a single previous psychotic illness following a cluster of seizures.
      This report shows a collaborative management of the neuropsychiatric
      complications of temporal lobe epilepsy (TLE), by the neurology, geriatric
      medicine and psychiatry teams.

PMID- 30200032
TI  - Improving monitoring for metabolic syndrome using audit.
AB  - Audit has been defined as "a quality improvement process that seeks to improve
      patient care and outcome, through systematic review of care and comparison with
      explicit criteria, followed by the implementation of change". As of May 2011,
      under the Medical Practitioners Act 2007, doctors are legally obliged to join in
      professional competence schemes, following requirements set by the Medical
      Council. These include the obligation for doctors to conduct one clinical audit
      per year. In Ireland and elsewhere, audit provides an opportunity for services to
      create an "environment in which clinical care will flourish".

PMID- 30200033
TI  - Mental health and the asylum process.

PMID- 30200034
TI  - Big boys don't cry: male secondary school students' attitudes to depression.
AB  - OBJECTIVES: In an earlier qualitative study we explored the attitudes of young
      men aged 15-19 (Group A) to mental health and, in particular, to engaging with
      the various mental health services available. We found that the participants
      perceived stigma in connection with mental ill health and they displayed
      particularly strong negative attitudes in relation to both doctors and
      medication. The investigation was then repeated with students who had been given
      a short (less than two-hour) programme called 'Beat the Blues' (BTB) about mental
      health (Group B) in order to assess the effect of that exposure by comparing the
      attitudes of the two groups of students. This present phase of the analysis is a
      quantitative examination of the written responses by both Groups A and B to an
      administered questionnaire. METHODS: A total of 42 young men took part in eight
      focus groups held in boys-only Dublin secondary schools, described in Burke et
      al. A questionnaire, administered to each participant, examined the students'
      attitudes to depression and mental illness. The results were analysed by computer
      using SPSS to search for any trends and any contrasts between groups A and B and
      among the different socio-economic groups (SEGs) within the sample. RESULTS:
      Almost no statistically significant differences were found between groups A and
      B. However, some differences were found among the SEGs. In particular, very
      significant differences (p < 0.01 in each case), were found in attitudes towards
      depression, with increasing support for statements such as "People with
      depression just need to snap out of it", "Drinking alcohol can help cure
      depression" and "Depression is only an excuse for laziness" found among the lower
      SEGs. A very high percentage of students indicated their desire to talk to
      someone in times of personal stress; this was almost always their best friend or
      their mother. However, most students said they would be uncomfortable if a friend
      raised such a topic. CONCLUSION: The main conclusion - that a single exposure to
      a positive programme about depression produces little or no effect - is hardly
      unexpected. Nonetheless, there are indications of a great willingness among older
      secondary students to learn about and discuss mental health issues. Furthermore,
      the highly negative attitudes among students from the lowest socio-economic group
      in this study would seem to indicate that the greatest need for education about
      mental health lies with working-class adolescents. Hence, it is recommended that
      a programme of multiple interventions be introduced into the senior cycle of
      secondary education.

PMID- 30200035
TI  - Mental health rehabilitation services in Ireland: vision and reality.
AB  - OBJECTIVES: The Irish national mental health policy document, A Vision for Change
      , included recommendations to develop specialist rehabilitation mental health
      services. This survey was conducted as part of a multicentre study to investigate
      current provision of mental health rehabilitation services in Ireland and factors
      associated with better clinical outcomes for users of these services. The aim was
      to carry out a detailed national survey of specialist rehabilitation services in
      order to describe current service provision. METHOD: A structured questionnaire
      was sent to consultant rehabilitation psychiatrists in all mental health
      catchment areas of Ireland that had any rehabilitation services to gather data on
      various aspects of service provision. RESULTS: Twenty-six of the 31 mental health
      areas of Ireland had some form of rehabilitation service. Sixteen teams working
      in 15 of these areas fulfilled A Vision for Change criteria to be defined as
      specialist rehabilitation services and all 16 responded to the survey. The
      overall response rate was 73% (19/26). Most services lacked a full
      multidisciplinary team. Only one service had an assertive outreach team with
      acceptable fidelity to the assertive outreach model. Urban services were less
      well resourced than rural services. CONCLUSION: This is the first national survey
      to describe the provision of mental health rehabilitation services in Ireland.
      Although there has been an increase in the provision of consultant-led specialist
      rehabilitation services nationally, these services lack multidisciplinary input.
      There also appears to be a lack of planned provision of the facilities required
      to provide comprehensive rehabilitation services with unequal distribution of
      resources between urban and rural areas. This has potential cost implications for
      local mental health services in relation to 'out of area treatment' placements
      and perhaps more importantly to the overall quality of patient care.

PMID- 30200036
TI  - Investigation of schema modes currently activated in patients with psychiatric
      disorders.
AB  - OBJECTIVES: To investigate schema modes currently activated in individuals with
      psychiatric disorders and to attain a greater understanding of healthy and
      dysfunctional schema modes in this population. Furthermore, we wish to ascertain
      if individuals who fulfil criteria for clinical (psychiatric) disorders with the
      Minnesota Multiphasic Personality Inventory (MMPI), also manifest dysfunctional
      modes and weaker healthy modes on the Schema Mode Inventory (SMI). METHOD: Fifty
      individuals were administered the MMPI and SMI during routine psychological
      assessments between September 2008 and June 2010. RESULTS: Both healthy schema
      modes (Happy Child (HC) and dysfunctional schema modes (Compliant Surrender (CS),
      Detached Self-soother (DSS) and Demanding Parent (DP)) were evident in this
      population. Positive correlations were noted between several dysfunctional schema
      modes from the Child, Maladaptive Coping and Maladaptive Parent domains of the
      SMI and several scales of the MMPI including: Depression (D), Psychopathic
      deviate (Pd), Masculine feminine (Mf), Paranoia (Pa), Psychasthenia (Ps), Mania
      (Ma), Schizophrenia (Sc), and Social introversion (Si) (p < 0.001). A negative
      correlation (p < 0.001) was found between the Healthy Adult (HA) and Happy Child
      (HC) schema modes of the SMI and the Hypochondriasis (Hs), Depression (D),
      Psychopathic deviate (Pd), Psychasthenia (Pt), and Social introversion (Si)
      scales of MMPI. CONCLUSION: This study demonstrates the presence of several
      dysfunctional schema modes in individuals with a wide range of clinical
      (psychiatric) disorders and a strong correlation between dysfunctional schema
      modes and clinical disorders of the MMPI. The SMI can aid in the assessment and
      understanding of individuals with a wide range of psychiatric disorders and can
      also form the basis for Schema Focused Therapy (SFT), a therapy showing promise
      for a number of clinical conditions, particularly borderline personality
      disorder.

PMID- 30200037
TI  - Prescription chart writing practices in an acute psychiatric unit.
AB  - OBJECTIVES: The survey was designed to evaluate the current prescribing practice
      of the doctors in our local psychiatric unit against the standards outlined by
      the National Health Office in the Code of Practice for Healthcare Records
      Management, and to assess the changes in practice by completing an audit cycle.
      METHOD: The survey was carried out in a 27 bed acute psychiatric unit. A single
      assessor reviewed 51 inpatient drug prescription charts using a standardised data
      collection form derived from the Code of Practice document. Results were
      presented to the relevant clinical staff and a repeat survey was conducted a few
      months afterwards. All data were categorical and the frequencies were computed
      using SPSS 13.0. RESULTS: A total of 51 medication prescription charts were
      analysed on each occasion during the period of the study. The information
      contained on the drug charts were assessed against explicit predefined criteria
      as per the approved standard. At the initial survey, allergy documentation was
      absent in 59% of charts, only 18% of charts had generic only prescriptions, 90%
      of 'as required' medication lacked review dates, and only 33% of charts were
      considered to be reasonably neat. The repeat survey showed improvements in these
      practices, generic only prescribing increased to 39%, and 55% of charts were
      considered to be reasonably neat by the assessor. CONCLUSION: Our study has
      identified deficiencies in prescribing practices and we have shown improvement in
      some of these practices at the repeat survey, however, further improvement is
      required. Given that the non-consultant hospital doctors are mostly involved in
      prescribing on drug charts, approved standards should be incorporated into the
      induction programme at the commencement of training in this unit. This standard
      should be monitored and maintained through the means of regular audits.

PMID- 30200038
TI  - Psychoeducation: priorities of service users and service providers.
AB  - OBJECTIVES: The objective of this study was to ascertain the topics patients and
      mental health professionals thought should be covered in a psychoeducation
      programme at a day hospital. METHODS: Patients at the psychiatric day hospital
      and mental health professionals were invited to complete the study questionnaire.
      Replies from 101 participants were analysed. RESULTS: The patients and mental
      health professionals generally agreed regarding the topics to be covered in the
      eight-week psychoeducation programme. Patients tended to score 'suicide' as more
      important than did the mental health professionals. CONCLUSIONS: Patients in a
      day hospital setting and mental health professionals share similar concerns about
      what information needs to be imparted about the patients' illnesses. However,
      suicide is seen by patients as a more important topic in such a setting.

PMID- 30200039
TI  - Informed consent in psychiatric practice: where does the law now stand?
AB  - There is an established ethical and legal duty upon psychiatrists to obtain
      informed consent before treating a patient, although some exceptions do apply
      under Mental Health Legislation. The required standard for informed consent has
      been the subject of important case law in Ireland and other common law
      jurisdictions and this has caused some uncertainty for clinicians. The standard
      of informed consent can be viewed from the point of view of what the medical
      profession thinks is appropriate, or alternatively from the position of what a
      patient would reasonably expect to be told. These contrasting approaches are
      discussed in detail. A recent decision of the Irish Supreme Court establishes the
      'patient-centred' standard for informed consent as the relevant standard in Irish
      law. The current legal position on informed consent is discussed in relation to
      common clinical scenarios in psychiatric practice.

PMID- 30200040
TI  - Dr Ada English: patriot and psychiatrist in early 20th century Ireland.
AB  - Dr Adeline (Ada) English (1875-1944) was a pioneering Irish psychiatrist. She
      qualified in medicine in 1903 and spent four decades working at Ballinasloe
      District Lunatic Asylum, during which time there were significant therapeutic
      innovations (eg. occupational therapy, convulsive treatment). Dr English was
      deeply involved in Irish politics. She participated in the Easter Rising (1916);
      spent six months in Galway jail for possessing nationalistic literature (1921);
      was elected as a Teachta Dala (member of Parliament; 1921); and participated in
      the Civil War (1922). She made significant contributions to Irish political life
      and development of psychiatric services during an exceptionally challenging
      period of history. Additional research would help contextualise her contributions
      further.

PMID- 30200041
TI  - An unusual cause of autobiographical memory loss.
AB  - We describe an unusual cause of autobiographical memory loss in a 55 year old man
      who presented with prominent memory loss for significant events in his life over
      a period of five years with evidence of patchy memory loss for events prior to
      this. It was associated with emotional lability and was complicated by a number
      of tragic events in his life in the previous four years. In addition there were a
      number of brief episodes (< 30 mins) where he would transiently lose his memory
      for events including for hours, days or months prior to the event.
      Neuropsychological assessment confirmed prominent autobiographical memory loss
      with minimal deficits in other domains. An electroencephalogram (EEG) revealed a
      simple partial seizure arising from the right temporal lobe, pointing to a
      diagnosis of Transient Epileptic Amnesia. He was commenced on anti-epileptic
      medication and responded both subjectively and objectively. There are
      approximately 94 cases of TEA described in the literature and the diagnostic
      criteria and postulated aetiology of this illness is discussed here. Clinicians
      need to have high index of suspicion of epilepsy when assessing a patient with
      prominent autobiographical memory impairments.

PMID- 30200042
TI  - Hypoprolactinaemic galactorrhoea in long-term methadone treatment.
AB  - Although hyperprolactinaemia is associated with galactorrhoea, galactorrhoea
      often occurs without any hyperprolactinaemia. This has been well established, and
      it has been documented in women prescribed/using methadone and other opiates. One
      case series described amenorrhoea and galactorrhoea in 'female heroin addicts',
      but it has not before been described in a patient with hypoprolactinaemia. We
      report a case of a 30 year old non-pregnant, non-puerperal, opioid-dependent, HIV
      positive woman on long-term methadone maintenance programme, who presented with
      bilateral, milky nipple discharge, associated with painful breast lumps, but with
      serum prolactin levels below the normal range. She was not prescribed any other
      medications likely to have effect on the endocrine system. This case highlights
      the need for prescribers to be alert to the implications of long-term use of
      opioids.

PMID- 30200043
TI  - Psychiatric training and research in Ireland.

PMID- 30200044
TI  - Reply to Dr O'Loughlin's letter.

PMID- 30200046
TI  - New long-stay psychiatric in-patients: a comparison of UK and Irish national
      audit.

PMID- 30200045
TI  - A model for primary mental healthcare in Ireland.

PMID- 30200047
TI  - Serotonin toxicity.
AB  - Serotonin toxicity is a potentially life-threatening condition associated with a
      range of psychotropic medications, co-administration of specific combinations of
      agents and overdose of certain drugs. It is associated with a wide diversity of
      clinical signs and symptoms, including cognitive, autonomic and somatic effects,
      as well as serious complications, including possible death. Diagnosis is often
      challenging and requires a high index of suspicion. Differential diagnosis
      includes syndromes such as neuroleptic malignant syndrome. Management depends on
      the causal agent and urgency of clinical presentation. Treatment may involve
      discontinuing the causal agent and providing supportive measures, or emergency
      intervention to preserve vital functions (airway, breathing, circulation),
      amongst other measures. Further research is needed to clarify the incidence of
      serotonin toxicity, issues related to differential diagnosis, optimal management
      of the condition, and treatment of mood problems following serotonin toxicity.

PMID- 30200048
TI  - A Perfect Demonstration of the Absence of Leadership: Alcohol Policy in Ireland.

PMID- 30200049
TI  - Methadone Treatment in Irish General Practice: Voices of Service Users.
AB  - This study sets out to make a meaningful and useful contribution to the
      discussion surrounding the treatment of heroin addiction in Ireland. The study
      took place in nine urban general practices in Dublin city. Twenty five service
      users were interviewed in-depth. A phenomenological approach drawing on the
      psychological research methods of Colazzi for data analysis informed this study.
      Four themes emerged from the data: Service users' the significance of methadone
      for the service user; service users' understanding of the Methadone Treatment
      Protocol and the experience of addiction and its effect on families. This paper
      reports on the experiences of service users receiving methadone treatment in
      urban general practice in Dublin and in so doing highlights the influence of the
      GP in supporting recovery. It explores the theme - Service User's Experience of
      attending general practice for methadone treatment. These accounts provide
      insight into the harm reduction policy of methadone maintenance and highlight how
      - from the service users' experience - the implementation is falling short.

PMID- 30200051
TI  - A Qualitative Study of Gender-Based Pathways to Problem Drinking in Dublin,
      Ireland.
AB  - OBJECTIVE: High rates of alcohol-related harm have been reported in the European
      Union, including Ireland, for more than 20 years. This article's goal is to
      contextualise such rates by examining gender-based pathways to alcohol use
      disorders from the perspective of those self-identifying as in recovery using
      data collected midway through this 20-year trend. METHODS: Sixteen informants
      (nine men and seven women) were interviewed between 1998 and 1999 in Dublin,
      Ireland. Using qualitative methods, informants were asked to reflect upon their
      experiences of problem drinking and recovery. RESULTS: Drinking expectancies, pub
      based socialising, social anxiety and perceived social expectations to drink were
      cited as common pathways to problem drinking by informants, highlighting
      contradictions in drinking practices and the symbolic functions of alcohol.
      Drinking contexts identified by informants were public pub-based drinking for men
      and home-based drinking for women. Primary barriers to problem acceptance
      centered on pub-based socialising norms and gender-based shame. Benefits of
      support group membership included establishing new social networks and learning
      alternative ways to cope with negative emotions. CONCLUSION: Consideration of
      drinking expectancies, the social contexts in which problematic drinking occurs,
      gender ideologies, the cultural meanings of drinking behaviours, and attention to
      feelings of isolation or loneliness experienced by those exhibiting problematic
      consumption behaviours might further understandings of potentially harmful
      drinking, especially in periods of economic uncertainty.

PMID- 30200050
TI  - Using Quantitative Research to Measure Recovery Outcomes and Correlates.
AB  - OBJECTIVE: Recovery has become an increasingly significant concept within mental
      health literature. Despite this, few studies have investigated the measurement of
      recovery and its correlates using quantitative methods. The aim of the current
      study was to measure recovery in people with chronic psychiatric disabilities
      using a quantitative tool and to investigate what factors were correlated to
      recovery outcomes. It was hypothesised that measures that investigated the
      individual's subjective sense of well-being would have a stronger correlation to
      recovery than more traditional clinician-rated scales. METHOD: Participants were
      63 people with a chronic psychiatric disability. They were recruited as a
      convenience sample from community mental health rehabilitation teams in three
      locations. Using a cross-sectional design, participants completed measures of
      psychological well-being (Psychological Well-being Scale (PWB); hope (Adult State
      Hope Scale) and recovery (Recovery Assessment Scale (RAS). Health professionals
      rated participants' psychosocial functioning using the Multnomah Community
      Ability Scale (MCAS-R). RESULTS: Analyses found that there was no significant
      correlation between clinician-rated psychosocial functioning scores and
      participant-rated recovery outcomes. Psychological well-being variables rated by
      the participants themselves were found to significantly correlate with recovery
      outcomes. The variables hope, environmental mastery and relationships with others
      were found to emerge as independent predictors of recovery scores. CONCLUSIONS:
      Results underscore the premise that recovery is a distinct construct that is
      unique to the individual and cannot be fully captured by objective measures of
      functioning. Implications for practice suggest that services for people with
      chronic psychiatric disability should utilise recovery focused tools in patient
      assessment and treatment in order for a comprehensive assessment to be achieved.
      Recovery interventions should also focus on the individual's hope, mastery and
      relationships with others in order to promote recovery.

PMID- 30200052
TI  - The Dark Cartoon: Intrusive Imagery Secondary to Childhood Sexual Abuse.
AB  - We report on the case of a middle-aged woman with a complex psychiatric history
      in whom atypical intrusive imagery identified in the mental status examination
      appeared to represent an emergence of childhood dissociative phenomena. These new
      symptoms led to the reappraisal of her clinical presentation and a diagnostic re
      evaluation that they represented a re-emergence of childhood post-traumatic
      stress disorder secondary to sexual abuse. We discuss the phenomenology
      identified in our patient with the aim of increasing awareness of unusual
      symptoms in adults with a history of childhood sexual abuse and the importance of
      the mental state examination in eliciting and classifying such phenomena.

PMID- 30200053
TI  - Burnout and its Effect on Neurocognitive Performance.
AB  - OBJECTIVES: The hypothesis that burnout is predictive of performance deficits on
      a number of neuropsychological tests was examined among a group of psychiatric
      nurses. A possible relationship between burnout and state and trait anxiety
      levels was also investigated. METHODS: A sample of psychiatric nurses (n=45)
      completed the Maslach Burnout Inventory (MBI) and the State-Trait Anxiety
      Inventory (STAI). Their performance on a number of neurocognitive tests from the
      Cambridge Neuropsychological Test Automated Battery (CANTAB) was examined. The
      neurocognitive tests measured visual memory, verbal memory and attention.
      RESULTS: Multiple regression analyses were conducted between the burnout
      subscales and the results of the neuropsychological tests, and also between the
      burnout subscales and both state and trait anxiety levels. No overall significant
      relationship was found between neurocognitive performance and burnout. However,
      trait anxiety was significantly predictive of each of the burnout subscales of
      emotional exhaustion, depersonalisation and also of decreased personal
      accomplishment. CONCLUSIONS: The levels of burnout were in the moderate range for
      all three subscales and so the population was suffering from burnout. The fact
      that the trait anxiety variable was predictive of all three of the burnout
      subscales suggests that predisposition towards anxiety may be a vulnerability
      factor among people who suffer from burnout.

PMID- 30200054
TI  - Analysis of Episodes of Involuntary Re-admission in Ireland (2007-2010).
AB  - OBJECTIVES: Initial examination of data held by the Mental Health Commission
      indicated a number of patients having repeated involuntary readmissions (defined
      as patients having three or more involuntary episodes in a calendar year). The
      Commission sought more empirical analysis of the data relating to these patients,
      to determine if there were any trends or commonality regarding their demographic
      characteristics, length of episode, and diagnoses. METHODS: From 1 November 2006
      the Mental Health Commission has been notified of all involuntary admissions in
      Ireland under the Mental Health Act (2001). From this national database
      information on patients who have had three or more involuntary admissions per
      year was analysed. RESULTS: In the period studied there has been an overall
      reduction in the number of voluntary and involuntary admissions to Irish
      psychiatric hospitals and units. However, the use of involuntary admission
      remains constant at around 10% of all admissions. Seven percent (n=569) of
      involuntary admission orders in this four year period relate to two percent
      (n=121) of all involuntary patients. Patients who have experienced repeated
      involuntary admissions are predominantly male (59%), often have a diagnosis of
      schizophrenia, or schizotypal and delusional disorders (57%), or mania (20%), are
      in the age band 22-64 (80%) and more often live in rural counties. CONCLUSIONS:
      Potential appears to exist to significantly reduce the number of involuntary
      admissions by focusing on the care given to patients who are repeatedly re
      admitted. More analysis is needed of voluntary and involuntary re-admissions if
      inpatient facilities are to be effectively configured.

PMID- 30200055
TI  - The Teamworking Challenges of Care Planning.
AB  - BACKGROUND: Care planning is a multidisciplinary process used to develop an
      individualised recovery plan for each service user. The success of this process
      will depend on the extent to which members of mental health teams can work with
      one another, with service users, and with other service providers in developing a
      coordinated plan that meets service user needs across multiple domains. AIMS:
      This paper examined the teamworking challenges that Community Mental Health Teams
      (CMHTs) face during the care planning process and how such challenges may be
      managed. METHOD: A narrative review of published articles and policy documents
      relevant to teamworking and recovery-focused care planning within mental health
      teams. FINDINGS: Teamworking challenges include the provision of integrated
      rather than fragmented care, the empowerment of the service user, and development
      of a distributed model of leadership, responsibility and decision making.
      CONCLUSIONS: CMHTs face a range of substantial but manageable challenges in
      attempting to implement recovery-focused care planning. Recommendations include
      the need to integrate recovery-orientated skills and values into professional
      training, the need for greater multidisciplinary training opportunities, and the
      need to evaluate CMHTs based on recovery-orientated criteria.

PMID- 30200056
TI  - Developing an Integrated Mental Health Care Service: Description of a Pilot
      Mental Health Consultation/Liaison Clinic in a Primary Care Centre.
AB  - : To determine if a consultation/liaison mental health clinic in primary care as
      proposed for Vision for Change, The Primary Care Strategy and the Department of
      Health is an efficient model of delivering mental health care in Ireland.
      METHODS: The pattern of service use and the clinical characteristics of new
      patients attending a pilot consultation/liaison clinic in a local primary care
      centre were studied. RESULTS: During the first 16 months of this clinic 1.2% of
      patients did not attend the initial assessment in the liaison clinic versus
      29.75% in the regular Outpatients Department (OPD). Less than one in five (17.1%)
      required a follow-up review with the clinician in the consultation/liaison clinic
      compared to almost all patients first seen in OPD secondary care (96.6%). A small
      minority of patients (6.1%) needed referral to secondary care due to the
      complexity of their presentation. CONCLUSIONS: A consultation/liaison mental
      health clinic in primary care results in an efficient use of manpower resources
      due to the low Did Not Attend (DNA) rates and low proportion of formal referrals
      to secondary care. As patients seem to favour this type of setting, over
      traditional outpatient departments, a move towards consultation/liaison clinics
      in the primary care team should be considered.

PMID- 30200057
TI  - Steroid-Induced Mania: A Case Report.
AB  - Corticosteroids are commonly used in the treatment of a variety of medical
      conditions in children and adolescents. However, adverse psychiatric side effects
      can occur which pose challenges in treatment of medical conditions. This case
      highlights some of these challenges, in particular the treatment of steroid
      induced psychiatric complications in Acute Lymphocytic Leukaemia (ALL). It also
      accentuates the importance of awareness among pediatricians of the potential
      adverse psychiatric effects when prescribing corticosteroids in this age group.
      Families need to be advised accordingly to ensure early recognition and
      treatment.

PMID- 30200058
TI  - Erratum.

PMID- 30200059
TI  - Is the combined application of both drain-clamping and tranexamic acid superior
      to the single use of either application in patients with total-knee
      arthroplasty?: A meta-analysis of randomized controlled trials.
AB  - BACKGROUND: To compare the efficacy and safety of the combined application of
      both drain-clamping and tranexamic acid (TXA) versus the single use of either
      application in patients with total-knee arthroplasty (TKA). METHODS: Databases
      (EMBASE, PubMed, Cochrane Library, Web of Sciences, the Google database, and the
      Ovid database) were searched from their inception through April 2018 for
      randomized controlled trials (RCTs) comparing the combined application of both
      drain-clamping and TXA versus single use of either application in patients with
      TKA. The Cochrane risk of bias (ROB) tool was used to assess the methodologic
      quality. The primary outcomes were blood loss in drainage, total blood loss,
      transfusion rate, and hemoglobin decline. The secondary outcomes were
      postoperative complications, the Knee Society Score (KSS), and the Western
      Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score. The
      statistical analysis was performed with RevMan 5.3.5 software. RESULTS: A total
      of five RCTs (479 participants) were included in our meta-analysis. The present
      meta-analysis indicated that significant differences existed in the total blood
      loss (mean difference [MD] = -145.86, 95% confidence interval [CI]: -228.64 to 
      63.08, P = .0006), blood loss in drainage (MD = -169.06, 95% CI: -248.56 to 
      89.57, P < .0001), hemoglobin decline (MD = -0.66, 95% CI: -1.00 to -0.33, P =
      .0001), and transfusion rate (MD = 0.44, 95% CI: 0.26-0.75, P = .002) between the
      groups. However, regarding postoperative complications, no significant
      differences were found between the 2 groups in the KSS and the WOMAC score (P >
      .05). CONCLUSION: Combined application of both drain-clamping and TXA was
      associated with significant reductions in blood loss in drainage, total blood
      loss, hemoglobin decline, and the need for transfusion. However, high-quality,
      well-designed RCTs with long-term follow-up are still required.

PMID- 30200060
TI  - A rare case of deep cerebral venous thrombosis secondary to traumatic epidural
      hematoma: Case report.
AB  - RATIONALE: Deep cerebral venous thrombosis (DCVT) is a rare disease, but always
      results in poor prognosis. PATIENT CONCERNS: We reported a 79-year-old female
      with coma after traumatic brain injury (TBI). DIAGNOSIS: The epidural hematoma
      was first diagnosed on non-contrast computerized tomography (CT). The hypodense
      areas in bilateral thalami and basal ganglia on reexamination CT highly indicated
      the suspicion of DCVT. Finally, the appearance of thrombosis of the vein of Galen
      on the computed tomography venography (CTA) and digital subtraction angiography
      (DSA) confirmed the diagnosis. INTERVENTIONS: The patients received surgery to
      remove the epidural hematoma. After that, she was treated with oral
      anticoagulation agent (low molecular weight heparin (LMWH), 180 Axal U/kg 24 h)
      for 4 weeks, shifted by oral warfarin (2.5 mg qd) for 4 weeks. OUTCOMES: The
      hypodense areas in bilateral thalami and basal ganglia have been largely
      reversed. At the time of 6 months after surgery, the patient could take care of
      herself. LESSONS: If the CT shows hypodense areas in bilateral thalami and basal
      ganglia, a diagnosis of DCVT should be suspected once the patients could not
      recover from the treatment of primary diseases.

PMID- 30200061
TI  - Acute intermittent porphyria presenting with seizures and posterior reversible
      encephalopathy syndrome: Two case reports and a literature review.
AB  - INTRODUCTION: Acute intermittent porphyria (AIP) is a rare and challenging
      hereditary neurovisceral disease with no specific symptoms. Posterior reversible
      encephalopathy syndrome (PRES) is a clinicoradiological syndrome with bilateral
      reversible posterior gyriform lesions that can be associated with many different
      conditions, including AIP. Usually, peripheral neuropathy is considered the most
      common neurological manifestation of AIP. However, AIP should also be considered
      when seizures and PRES are associated with unexplained abdominal pain. CASE
      PRESENTATION: Both the patients were presented with seizures and PRES on brain
      magnetic resonance imaging (MRI). Unexplained abdominal pain occurred before the
      onset of seizures. The AIP diagnosis was made after repeated Watson-Schwartz
      tests. Hematin was not available for these 2 patients. However, supportive
      treatment including adequate nutrition and fluid therapy as well as specific
      antiepileptic drugs aided the patient's recovery and no acute attacks had
      occurred by the 3-year follow-up. CONCLUSION: In contrast to other causes of PRES
      patients, seizure is the most common symptom in AIP patients with PRES. This is a
      strong diagnostic clue for AIP when ambiguous abdominal pain patients presented
      with seizures and PRES on brain MRI. A positive prognosis can be achieved with
      the combination of early recognition, supportive and intravenous hematin therapy,
      and withdrawal of precipitating factors, including some antiepileptic drugs.

PMID- 30200062
TI  - Dietary fiber intake and risks of proximal and distal colon cancers: A meta
      analysis.
AB  - The purpose of this study was to conduct a systematic review and meta-analysis of
      studies investigating the relationship between dietary fiber intake and subsite
      specific colon cancer.The PubMed database was searched to identify relevant
      cohort studies published from inception to August 2016 in order to examine
      individually the association between dietary fiber intake and the risk of
      proximal colon cancer (PCC), and that between dietary fiber intake and the risk
      of distal colon cancer (DCC). We searched the reference lists of the studies
      included in our analysis as well as those listed in the published meta-analyses.
      A random-effects model was used to compute summary risk estimates. Heterogeneity
      was assessed using I and Q statistics. Publication bias was assessed with the
      Egger's and Begg's tests, with a P value of P < .10 indicating publication bias.
      All statistical tests were 2-sided.We identified and included 11 prospective
      cohort studies in the final meta-analysis. The risks of PCC and DCC among
      individuals in the highest dietary fiber intake quartile/quintile were 14%
      (relative risk [RR] = 0.86, 95% confidence interval [CI] = 0.78-0.95) and 21% (RR
      = 0.79, 95% CI = 0.71-0.87) lower, respectively, than those among individuals
      with the lowest dietary fiber intake. In a subgroup analysis, the inverse
      association observed in the sex-based subgroup was apparent only for men with
      PCC. Dietary fiber intake was inversely associated with DCC for both men and
      women. In addition, dietary fiber intake appeared to be inversely associated with
      PCC only in European countries, whereas this association was observed for DCC in
      both European countries and the United States.Our findings reveal that dietary
      fiber intake is associated inversely with the risk of both PCC and DCCs.

PMID- 30200063
TI  - Short interval of biopsy to robotic-assisted laparoscopic radical prostatectomy
      does not render any adverse effects on the perioperative outcomes.
AB  - The aim of our study was to investigate the effects of prostate biopsy on
      perioperative outcomes of robotic-assisted laparoscopic prostatectomy (RALP).A
      total of 181 patients who underwent the RALP in our institution have been
      retrospectively reviewed, patients were divided into different groups according
      to the interval of biopsy to RALP and core numbers of biopsy. Perioperative
      outcomes including estimated blood loss (EBL), operative time (OT), surgical
      margin status, postoperative drainage, hospital stay, and perioperative
      complications were served as endpoints.Interval of biopsy to RALP was not
      significantly correlated with any perioperative outcomes, while the biopsy core
      numbers had significant correlation with the EBL. In logistic regression
      analysis, the biopsy core numbers were associated with higher risk of positive
      surgical margins. Body mass index (BMI) was also a significant factor related to
      OT.Delay of the RALP after biopsy was not applicable in the era of RALP and
      surgeons could be more freely in selecting the time of RALP. Besides, further
      studies should focus on how to improve the diagnostic efficiency of prostate
      cancer without increasing the incidence of surgical complications.

PMID- 30200064
TI  - Endoscopic ultrasound (EUS) elastography and strain ratio, could it help in
      differentiating malignant from benign pancreatic lesions?
AB  - Evaluating the role of endoscopic ultrasound (EUS) elastography and strain ratio
      in differentiation between malignant and benign pancreatic lesions.Three hundred
      twenty-five patients with solid pancreatic lesions were enrolled in this
      prospective study from 2014 to 2017. EUS real-time elastography scoring and
      strain ratio were done to all patients and compared to the final diagnosis to
      assess its sensitivity, specificity, positive and negative predictive values (PPV
      and NPV) in differentiating malignant from benign lesions.A cut-off value of 4.2
      we had sensitivity of 95%, specificity of 63%, PPV of 89%, NPV of 81%, and
      accuracy of 87%. Another cut-off value of 10.9 showed a sensitivity of 75%,
      specificity of 88%, PPV of 95%, NPV of 54%, and accuracy of 79%. Adding the
      elastography to the better cut-off value gave a sensitivity of 97%, specificity
      of 63%, PPV of 89%, NPV of 88%, and accuracy of 89%.Real-time elastography and
      strain ration are valuable in differentiating malignant from pancreatic lesions.

PMID- 30200065
TI  - Primary cervical disc arthroplasty versus cervical disc arthroplasty adjacent to
      previous fusion: A retrospective study with 48 months of follow-up.
AB  - The outcomes of cervical disc arthroplasty (CDA) following a previous fusion are
      ill -defined. The aim of this study was to share our experience and to assess mid
      term outcomes in patients receiving CDA adjacent to a previous fusion compared
      with primary CDA.Patients with cervical radiculopathy and/or myelopathy or
      patients who had undergone a previous cervical fusion surgery and had developed
      adjacent segment disease (ASD) between January 2008 and April 2013 were enrolled.
      Clinical and radiographic outcomes were compared for patients undergoing CDA at a
      level adjacent to a previous fusion (previous group) and those undergoing primary
      CDA (primary group).Fifty-two patients in the primary group and 9 patients in the
      previous group had adequate follow-up data. The mean follow-up periods were 61.96
      months and 61.78 months, respectively. The clinical outcomes all significantly
      improved after surgery, and no significant difference was found between groups.
      The disc height and range of motion of the operated level were preserved, and the
      values were similar between groups. Subsidence occurred in 2 (3.8%) patients in
      the primary group and 1 (11.11%) patient in the previous group. Heterotopic
      ossification (HO) was detected in 4 (44.44%) patients in the previous group and
      18 (34.62%) patients in the primary group. None of the patients required
      reoperation.Patients treated with a Prestige-LP disc maintained improved clinical
      outcomes and segmental motion in both the primary and previous groups.
      Additionally, CDA-treated patients who had a previous fusion surgery could safely
      undergo the surgery with complication rates similar to that of the first CDA
      surgery after 48 months of follow-up. CDA adjacent to a previous fusion may be an
      alternative treatment strategy in the future.

PMID- 30200066
TI  - Acute flaccid myelitis associated with enterovirus D68 infection: A case report.
AB  - RATIONALE: We present the first case of enterovirus (EV) D68, lineage B3
      infection, associated with acute flaccid myelitis (AFM) in Taiwan. AFM caused by
      EV D68 is relatively rare. This report highlights the importance of clinical
      recognition of the disease and discusses treatments that can benefit such
      patients. PATIENT CONCERNS: A 5-year-old boy experienced sudden onset of acute
      flaccid paralysis (AFP) involving left arm after fever and respiratory symptoms
      for 3 days. DIAGNOSES: Magnetic resonance imaging (MRI) of the spinal cord
      revealed signal changes over segments C1 to T5 on a T2-weighted image (T2WI),
      compatible with the diagnosis of AFM. The EV D68 strain, cultured from the throat
      of the patient was identified. INTERVENTIONS: We administered intravenous
      immunoglobulin (IVIG, 1g/kg, twice), pulse steroid therapy (methylprednisolone,
      30 mg/kg, twice) and oral prednisolone (1mg/kg/day). Rehabilitation was also
      arranged. OUTCOMES: The patient still had mild muscle atrophy over left arm after
      following-up for 1 year. LESSONS: Early diagnosis and prompt management are
      essential for managing this kind of patient. IVIG, pulse therapy, and oral
      prednisolone may play crucial roles in controlling its clinical course.

PMID- 30200067
TI  - Effect of single-dose intravenous dexamethasone on subjective voice quality after
      thyroidectomy: A meta-analysis.
AB  - BACKGROUND: Corticosteroids are widely used to treat voice change after
      thyroidectomy. In this study, we evaluated the effect of a single dose of
      intravenous dexamethasone after thyroidectomy using a metaanalysis. METHODS:
      Relevant studies were identified by searching the following databases: Medline,
      Embase, and Cochrane through February 2017. We followed PRISMA guidelines. The
      following search terms were used: "thyroidectomy," "voice," "steroid." Random
      effects models were used to estimate standardized mean differences (SMDs) and 95%
      confidence intervals. RESULTS: Our search yielded one retrospective cohort study
      involving 122 thyroidectomy patients and 3 randomized controlled studies
      involving 242 thyroidectomy patients. The pooled SMD for voice quality after
      thyroidectomy was -0.80 (P < .05). Subgroup analysis showed significant voice
      quality change 1 day after administration of dexamethasone. CONCLUSIONS: Single
      dose intravenous dexamethasone after thyroidectomy significantly improves
      subjective voice quality on day 1. The effect was not different significantly
      after day 1. LEVEL OF EVIDENCE: Level 2a.

PMID- 30200068
TI  - Craniocervical computed tomography angiography with adaptive iterative dose
      reduction 3D algorithm and automatic tube current modulation in patients with
      different body mass indexes.
AB  - The aim of this study was to investigate the feasibility of head and neck
      computed tomography angiography (CTA) using the 80-kV tube voltage and the
      adaptive iterative dose reduction (AIDR) 3D algorithm in patients with different
      body mass indexes (BMIs).From November 2016 to January 2017, 128 consecutive
      patients scheduled for head and neck CTA examinations were randomized into the
      100-kV group (n = 60) and the 80-kV group (n = 68). Both groups used the
      automatic tube current modulation technique and the AIDR 3D algorithm. The
      patients were further grouped as slender (BMI < 22 kg/m), normal weight (22
      kg/m<=BMI < 25 kg/m), and overweight (BMI >=25 kg/m). The image quality and the
      radiation dose of each subgroup were analyzed.The images of the head and neck
      vessels and the brain tissue obtained with 100 kV were all of diagnostic quality.
      Slender and normal weight patients imaged with 80 kV also produced images of
      diagnostic quality. However, 80 kV in the overweight patients failed to produce
      images of diagnostic quality. The radiation dose in the patients imaged with 80
      kV was significantly decreased in comparison with those imaged with 100 kV. The
      effective dose was 0.36 +/- 0.06 and 0.41 +/- 0.05 mSv in the slender and normal
      weight patients imaged with 80 kV.Head and neck CTA scanning with 80 kV,
      automatic tube current modulation, and AIDR 3D algorithm can produce high quality
      images with reduced radiation dose in slender or normal weight patients.

PMID- 30200069
TI  - Thoracic outlet syndrome (TOS): A case report of a rare complication after Nuss
      procedure for pectus excavatum.
AB  - RATIONALE: The Nuss procedure has become a major alternative operation for
      patients with pectus excavatum (PE). PATIENT CONCERNS: We report a case of 27
      year-old man with PE who developed thoracic outlet syndrome (TOS) after the Nuss
      procedure. The patient showed clinical symptoms of brachial plexus compression.
      DIAGNOSES: Further evaluation demonstrated a narrowed space between the first rib
      and the anterior scalene muscle and compressing the brachial plexus and vessels.
      INTERVENTIONS: Nerve nourishing medicine and rehabilitation exercising were taken
      to restore the muscle strength. OUTCOMES: Several months later, the clinical
      symptoms disappeared. LESSONS: Medicine and rehabilitation exercising may benefit
      the functional recovery of impaired nerve in TOS in the early stage of TOS.

PMID- 30200071
TI  - Comparison and correlation between the pediatric Voice Handicap Index and the
      pediatric voice-related quality-of-life questionnaires.
AB  - The aim of this study was to investigate differences and correlations between the
      pediatric Voice Handicap Index (pVHI) and the pediatric Voice-Related Quality-of
      life (pVRQOL) questionnaires in children with and without voice disorders. This
      was a cross-sectional study.A total of 418 parents with children aged 2 to 14
      years participated in this study from May 2016 to July 2017. This included 221
      parents of children with voice disorders (dysphonic group) and 197 parents of
      children without voice disorders (control group). The scores for the pVHI and the
      pVRQOL were compared, and correlation analysis was performed.Compared with the
      control group, the dysphonic group had a significantly higher total score and
      subscale scores for the pVHI (P < .001), and significantly lower pVRQOL scores (P
      < .001). The pVHI showed greater differences in subscale scores among the three
      dysphonic subgroups than the pVRQOL. The Spearman correlation coefficient between
      the pVHI and pVRQOL was -0.844 (P < .001). The total scores for the pVHI and
      pVRQOL also correlated significantly for each diagnostic category (P <
      .001).Voice-related quality of life was poorer in children with voice disorders
      than in those without voice disorders. The pVHI and pVRQOL scores were moderately
      to strongly correlated. These may be useful tools for assessing the voice
      related quality of life in children. The pVHI may provide more useful details
      about the effects of different types of voice disorders on the voice-related
      quality of life than the pVRQOL.

PMID- 30200070
TI  - Effect of educational interventions on health in childhood: A meta-analysis of
      randomized controlled trials.
AB  - BACKGROUND: The purpose of this study was to summarize the evidences from
      randomized controlled trials (RCTs) investigating the effects of educational
      interventions in overweight/obesity childhood by using meta-analytic approach.
      METHODS: PubMed, Embase, and the Cochrane Library databases were searched from
      the inception to April 2018. Weighted mean differences (WMDs) with corresponding
      95% confidence intervals (CIs) were used to measure the effects of educational
      interventions during childhood in the random-effects models. RESULTS: Thirty RCTs
      reporting data on 35,296 children were included in the meta-analysis. The summary
      WMD indicated that children received educational interventions had lower levels
      of body mass index (BMI) (WMD: -0.15; 95% CI: -0.24 to -0.05; P = .003), BMI z
      score (WMD: -0.03; 95% CI: -0.05 to -0.02; P < .001), waist circumference (WMD: 
      0.97; 95% CI: -1.95 to -0.00; P = 0.050), triceps skinfold (WMD: -1.39; 95% CI: 
      2.41 to -0.37; P = .008), systolic blood pressure (WMD: -1.13; 95% CI: -2.20 to 
      0.07; P = .037), total cholesterol (WMD: -4.04; 95% CI: -7.18 to -0.90; P =
      .012), and triglyceride (WMD: -2.62; 95% CI: -4.33 to -0.90; P = .003). However,
      educational interventions were not associated with the levels of waist-to-hip
      ratio, diastolic blood pressure, high-density lipoprotein, and low-density
      lipoprotein. CONCLUSION: The study findings elucidate the positive effects of
      educational interventions on BMI, BMI z-score, waist circumference, triceps
      skinfold, systolic blood pressure, total cholesterol, and triglyceride.

PMID- 30200073
TI  - Incidental finding of a breast carcinoma on Ga-68-DOTA-1-Nal3-octreotide positron
      emission tomography/computed tomography performed for the evaluation of a
      pancreatic neuroendocrine tumor: A case report.
AB  - RATIONALE: Functional imaging using radiolabeled somatostatin analogues plays an
      important role in the management of patients with neuroendocrine tumors, and it
      is a promising tool in the new era of theragnosis and personalized medicine.
      PATIENTS CONCERNS: The authors present the case of a 63-year-old woman referred
      for evaluation of a suspected pancreatic neuroendocrine tumor by Ga-68-DOTA-1
      Nal3-octreotide positron emission tomography/computed tomography (Ga-68-DOTA-NOC
      PET/CT). DIAGNOSES: PET/CT confirmed increased uptake of Ga-68-DOTA-NOC in a
      pancreatic lesion compatible with hyperexpression of somatostatin receptors in a
      neuroendocrine tumor. Furthermore, PET/CT revealed increased uptake in a breast
      lesion and in lymphadenomegalies (less intense than in the pancreatic tumor),
      which conducted to the incidental diagnosis of a breast carcinoma with lymph node
      metastases. INTERVENTIONS: For the breast cancer, the patient
      underwentneoadjuvant chemotherapy and anti-HER2 monoclonal antibody, after which
      she was submitted to surgery. Regarding thepancreatic neuroendocrine tumor, it
      was decided to maintain itunder surveillance. OUTCOMES: Breast carcinomas are
      known to express somatostatin receptors and this is the first report of Ga-68
      DOTA-NOC uptake in a breast tumor. LESSONS: Ga-68-DOTA-NOC PET/CT could be useful
      for the management of breast cancer patients in the new era of theragnosis and
      personalized medicine.

PMID- 30200072
TI  - Arterial stiffness but not endothelial dysfunction is associated with multidrug
      antihypertensive therapy and nondipper blood pressure pattern in kidney
      transplant recipients.
AB  - Vascular injury related to chronic kidney disease results in increased arterial
      stiffness and endothelial dysfunction which may affect arterial blood pressure
      (BP) and influence patient and graft survival in kidney transplant recipients
      (KTRs).This cross-sectional study aims to elucidate the relationship between the
      above-mentioned measures of vascular damage and effectiveness of antihypertensive
      treatment in KTR.One hundred forty-five KTRs 7.6 +/- 2.7 years after
      transplantation were enrolled in our study. Pulse wave velocity (PWV), flow
      mediated dilation (FMD), and nitroglycerin-mediated dilation (NMD) were measured,
      and 24-hour ambulatory BP monitoring was performed.Overall, there were 62
      patients with well-controlled or borderline BP and 83 subjects who did not
      achieve target BP despite antihypertensive treatment. Patients with suboptimal BP
      control were characterized by greater PWV (median 9.6/interquartile range: 3.9 vs
      8.0/3.3 m/s, P = .002), but borderline lower FMD (8.4% +/- 5.0% vs 9.9% +/- 5.7%;
      P = .09) as compared with the group with better BP control. When patients were
      allocated to subgroups based on the number of current antihypertensive
      medications, no differences in FMD and NMD were found. However, a significant
      trend was observed for higher PWV values and decreased proportion of dippers
      along with the increasing number of drugs. PWV, diabetes, and total cholesterol
      level, but not FMD or NMD, were explanatory variables for systolic BP in
      multivariate analysis.Arterial stiffness but not endothelial dysfunction is
      associated with suboptimal BP control in stable KTRs. Less efficient
      antihypertensive treatment appears to be caused by inadequate control of
      nocturnal BP.

PMID- 30200074
TI  - Association of elevated blood serum high-sensitivity C-reactive protein levels
      and body composition with chronic kidney disease: A population-based study in
      Taiwan.
AB  - Chronic kidney disease (CKD) is a risk factor for cardiovascular diseases and is
      associated with an increase in all-cause mortality. Studies regarding association
      among various body compositions in different inflamed states and the risk of CKD
      were rare. We aimed to evaluate the relationship among body composition, high
      sensitivity C-reactive protein (hsCRP) level, and the risk of CKD.This was a
      retrospective cross-sectional study using annual health examination data from 2
      medical centers in northern and southern Taiwan between January and December
      2015. We performed a variance analysis of the estimated glomerular filtration
      rate (eGFR) distribution in groups based on hsCRP and body fat percentage (BFP),
      and a multivariate logistic regression model was used to assess the relationship
      among BFP, hsCRP levels, and CKD.A total of 10,267 subjects aged >=18 years
      undergoing health examination were analyzed. In our study, overweight/obese
      patients were associated with increased risk of CKD. Nevertheless, in subjects
      with elevated hsCRP level, overweight/obese group with a higher BFP had a lower
      risk of CKD as compared with overweight/obese with normal BFP group (for BMI ? 23
      kg/m, high BFP/high hsCRP: odds ratio [OR] for CKD 1.86, 95% confidence interval
      [CI] = 1.10-3.17, P = .02; normal BFP/high hsCRP group: OR 2.32, 95% CI = 1.23
      4.37, P = .01) after adjusting for various confounders.Our findings suggest that
      various body compositions in different inflamed states may interfere with the
      risk of CKD. These results provide an important method for the early detection of
      impaired renal function by identifying various body compositions and inflammation
      states to detect CKD at an earlier stage.

PMID- 30200075
TI  - STROBE-A preliminary investigation of IVIM-DWI in cardiac imaging.
AB  - This study aims to explore the possibility to apply intravoxel incoherent motion
      magnetic resonance imaging (IVIM-MRI) in cardiac imaging.Multi-b-value diffusion
      weighted imaging (DWI) sequence scanning was performed on 12 healthy volunteers.
      A double exponential model was adopted, and the b-value sequence was 0, 20, 60,
      80, 120, 200, and 600 second/mm. The D-value, D*-value, and f-value of the
      anterior posterior and lateral walls of the ventricular septum were respectively
      measured on the short axis section of the heart, the parameters of the myocardium
      in different blood supply areas in each segment were recorded, and the measured
      data of these different segments were compared using analysis of variance.Among
      these 12 healthy volunteers, the D-value, D*-value, and f-value of these 72
      segments were not exactly equal, the D-values of the myocardium in the 5th and
      11th segment were lower than those in the 2nd, 3rd, 8th, and 9th segments, and
      the pairwise differences were statistically significant (P < .001). Furthermore,
      the difference in D-value between the 5th and 11th segments was not statistically
      significant (P = 1.000). The D*-value and f-value of the myocardium in the 5th
      and 11th segment were higher than those in the 2nd, 3rd, 8th, and 9th segments,
      and the pairwise differences were statistically significant (P < .001).
      Furthermore, the differences in D*-value and f-value between the 5th and 11th
      segments was not statistically significant (P = .214, .787).The intravoxel
      incoherent motion diffusion-weighted imaging (IVIM-DWI) technique can
      quantitatively reflect the diffusion and blood perfusion status of the
      myocardium.

PMID- 30200076
TI  - Comparisons between magnetic resonance/ultrasound fusion-guided biopsy and
      standard biopsy in the diagnosis of prostate cancer: A prospective cohort study.
AB  - Prostate-specific antigen is not useful for detection of prostate cancer in
      Chinese men. The major problems in prostate cancer patients are overdiagnosis and
      overtreatment. The objective of the study was to test the hypothesis that
      targeted biopsy is an accurate diagnostic tool for prostate cancer detection than
      standard biopsy in Chinese men.Total, 998 patients whom multiparticulate
      multiparametric magnetic resonance imaging had revealed at least 1 lesion in the
      prostate were included in a cohort. Patients were subjected to magnetic resonance
      imaging (MRI)/ultrasound (US) fusion-guided biopsy followed US-guided biopsy.
      Benefits of a diagnostic test were evaluated by decision curve analysis. Patients
      who were diagnosed as having prostate cancer by either of biopsies were subjected
      to radical prostatectomies followed by whole-mounted pathology (n = 578).
      Spearman rank correlation was performed between the biopsy results and the
      subtype of prostate cancer at 99% of confidence level.With respect to whole
      mounted pathology, for US-guided biopsy, MRI/US fusion-guided biopsy, and
      combined data of both biopsies, sensitivities were 0.973, 0.983, and 0.973 and
      accuracies were 0.837, 0.91, and 0.917, respectively. MRI/US fusion-guided biopsy
      (P = .165) and combined data of both biopsies (P = .182) had the same specificity
      to whole-mount pathology. However, a US-guided biopsy had not the same
      specificity to whole-mount pathology (P = .0003). Decision-making zones for
      radical prostatectomy of different biopsies were in the order of combined data of
      both biopsies >MRI/US fusion-guided biopsy >US-guided biopsy.Only the targeted
      biopsy is recommended for the diagnosis of prostate cancer.

PMID- 30200077
TI  - Comparative gene expression profile and DNA methylation status in diabetic
      patients of Kazak and Han people.
AB  - We attempted to investigate the mechanism and susceptibility genes for diabetes
      in Han and Kazak ethnic individuals.The abdominal omental adipose tissues were
      obtained from diabetic cases and healthy controls. The gene expression and
      methylation data were produced for Kazak and Han individuals, respectively, and
      analyzed by bioinformatics analysis.We obtained 921 differentially expressed
      genes (DEGs) in Han group and 1772 in Kazak group. DEGs in Han group were
      significantly related with type 2 diabetes mellitus, and biosynthesis of amino
      acids, while the DEGs specific to Kazak patients were significantly enriched in
      metabolism-related pathways such as carbon metabolism, propanoate metabolism, and
      2-oxocarboxylic acid metabolism. Major facilitator superfamily domain containing
      1 (MFSD1) was found to be a methylation associated gene at hypermethylation site
      of cg16289538 in Han group. Rho guanine nucleotide exchange factor 1 (ARHGEF1)
      was the susceptible gene corresponding to the methylation sites of cg18800192 and
      cg00759295 in Kazak group. ARHGEF1 was also a node in protein-protein interaction
      network and significantly enriched in hsa04270: vascular smooth muscle
      contraction pathways.The molecular mechanism of diabetes may be different in Han
      and Kazak patients. MFSD1 and ARHGEF1 may be the diabetes susceptible genes.

PMID- 30200079
TI  - A case report on Herlyn-Werner-Wunderlich syndrome with spontaneous abortion.
AB  - INTRODUCTION: Herlyn-Werner-Wunderlich syndrome (HWWS) is a rare congenital
      abnormality of the urogenital tract characterized by uterus didelphys, obstructed
      hemivagina, and ipsilateral renal agenesis. It is usually diagnosed after
      menarche, with a clinical presentation of dysmenorrhea, recurrent abdominal pain,
      and irregular menses. However, it is rare to diagnose it during pregnancy,
      subsequently resulting in spontaneous abortion. CASE PRESENTATION: A 22-year-old
      Chinese woman with HWWS whose left uterine pregnancy underwent spontaneous
      abortion presented with a right perforated obstructed hemivagina and right renal
      agenesis. The right vaginal septum was resected and the hematocolpos was drained,
      thereby relieving lower abdominal pain and preserving future fertility.
      CONCLUSION: Co-presentation of unilateral renal agenesis and uterus didelphys
      should encourage clinicians to rule out HWWS. Early diagnosis and subsequent
      treatment can avoid possible serious complications.

PMID- 30200078
TI  - Maintenance of low disease activity and remission with etanercept-disease
      modifying antirheumatic drug (DMARD) combination therapy compared with treatment
      with DMARDs alone in Latin American patients with active rheumatoid arthritis:
      Subset analysis of a randomized trial.
AB  - BACKGROUND: Current guidelines on the treatment of rheumatoid arthritis (RA)
      recommend early therapy targeting the achievement of low disease activity (LDA)
      or clinical remission. Little published information is available on the success
      of this treatment strategy in Latin America. In a subset analysis of patients
      from Latin America, we compared efficacy maintenance with etanercept 50 mg once
      weekly (ETN50) versus placebo (PBO), on a background of methotrexate (MTX) +/-
      other non-biologic, disease-modifying antirheumatic drugs, in patients with
      moderate-to-severe RA who had achieved LDA with ETN50. METHODS: In the Treat-to
      Target trial, adult patients with active RA nonresponsive to MTX were treated
      with ETN50 for 24 weeks (Period 1). Patients achieving LDA were randomized to
      receive ETN50 or PBO for 28 additional weeks (Period 2). The proportion of
      patients maintaining LDA at week 52 and other efficacy and quality-of-life
      measures were assessed. Descriptive statistics are presented using last
      observation carried forward imputation of data. RESULTS: Of the 64 patients from
      Latin America treated in Period 1, 61 (95.3%) achieved LDA. Among patients
      receiving ETN50, 13/34 remained in LDA and 6/14 maintained remission at week 52
      versus 6/27 and 4/10 patients receiving PBO. The median time to flare was 113
      days and 33 days for the ETN50 and PBO groups, respectively. In the overall
      population, adverse events were reported in 37% and 43%, serious adverse events
      in 1% and 4%, and serious infections in 0% and 2% of patients in the ETN50 and
      PBO groups, respectively. CONCLUSIONS: In patients with RA from Latin America,
      continuing treatment with ETN50 after achieving LDA appears to result in a higher
      proportion of patients maintaining LDA and remission compared with switching to
      PBO. CLINICALTRIALS. GOV REGISTRATION: NCT01578850.

PMID- 30200080
TI  - EORTC risk tables are more suitable for Chinese patients with nonmuscle-invasive
      bladder cancer than AUA risk stratification.
AB  - BACKGROUND: Patients with non-muscle-invasive bladder cancer (NMIBC) need
      accurate estimations of the risk of recurrence and progression. Physicians can
      offer individualized therapy after identifying high-risk tumors. In our study, we
      compared the applicability of European Organization for Research and Treatment of
      Cancer (EORTC) risk tables and American Urological Association (AUA) risk
      stratification in Chinese patients with NMIBC. METHODS: We retrospectively
      studied 301 patients with NMIBC who underwent transurethral resection of bladder
      tumor (TURBT) between October 2000 and July 2009 at Huashan Hospital of Fudan
      University and analyzed their parameters. The recurrence and progression rates at
      1 and 5 years postoperatively were calculated along with 95% confidence
      intervals. We compared them with results obtained from the EORTC risk tables and
      AUA risk stratification. P values <.05 were considered statistically significant.
      RESULTS: The median patient age was 67 years (21-92 years) and the median follow
      up duration was 46 months (2-151 months). We used EORTC risk tables to classify
      patients into 3 groups, depending on whether they suffered recurrence or
      progression after TURBT. Kaplan-Meier curves showed significant differences among
      the 3 recurrence-free survival (RFS) levels (P < .0001, log-rank test) and among
      the 3 progression-free survival (PFS) levels (P < .0001, log-rank test). AUA risk
      stratification showed the same results. Both classifications were suitable to
      predict recurrence and progression in Chinese patients. However, for high-risk
      patients in both series, Kaplan-Meier curves showed significant differences
      between RFS levels (P < .0001, log-rank test) and between PFS levels (P < .0001,
      log-rank test). EORTC risk tables were stricter and AUA was more sensitive in
      assigning patients to a high-risk group. CONCLUSION: EORTC risk tables are better
      than AUA risk stratification for predicting recurrence and progression in Chinese
      patients with NMIBC, especially among high-risk patients.

PMID- 30200081
TI  - Tibial plateau fractures (AO type B3) combined with tibial tubercle fracture:
      Case report and review of the literature.
AB  - RATIONALE: Tibial tuberosity fractures most often occur in the adolescents.
      Fracture of tibial tuberosity in adults is extremely rare with only 5 reported
      cases till date. Tibial plateau fractures combined with tibial tubercle fractures
      are not common. PATIENT CONCERNS: We report here a type B3 tibial plateau
      fracture (AO classification) with a concomitant fracture of tibial tuberosity.
      DIAGNOSES: Anteroposterior and lateral knee view radiographs revealed a complex
      comminuted fracture of the right tibial plateau (AO Type B3; Schatzker Type IV)
      with tibial tubercle fracture. Three-dimensional computed tomography (CT) showed
      that the tibial media plateau was split into 2 pieces in the sagittal plane,
      along with the isolated tibial tubercle. INTERVENTIONS: The open procedure was
      performed first and a standard posteromedial approach for medial and
      posteromedial tibial plateau fracture was used with double locking plate
      fixation. The tibial tuberosity was fixed with a cortical screw. OUTCOMES: The
      patient showed full range of motion in right knee after 8 weeks. The patient was
      allowed full weight bearing at 4 months. Eight months after operation, he was
      asymptomatic, showed a full range of motion and good strength. He had returned to
      work with no limitations. LESSONS: Fractures of the partial tibial plateau
      combined with tibial tubercle are present and should not be ignored. Accurate
      diagnosis and proper treatment will help achieve favorable outcomes in these
      patients.

PMID- 30200082
TI  - Acquired Fanconi syndrome secondary to light chain deposition disease associated
      with monoclonal gammopathy of renal significance: A case report.
AB  - RATIONALE: Renal Fanconi syndrome (FS) is a rare complication of monoclonal
      gammopathy. It is characterized by the impairment of renal proximal tubular
      function leading to normoglycemic glycosuria, aminoaciduria, hypophosphatemia,
      hypouricemia and proximal renal tubular acidosis. Renal impairment in monoclonal
      gammopathy, without fulfilling the criteria of multiple myeloma, is categorized
      as monoclonal gammopathy of renal significance (MGRS). PATIENT CONCERNS: A 54
      year-old male presented with progressively aggravated bone pain and limitation of
      activity was admitted to our department. A proximal renal tubular damage was
      suggested by hypophosphatemia, compensated metabolic acidosis, renal glycosuria,
      aminoaciduria, and hypouricemia. M-protein of IgA kappa was detected by
      immunofixation electrophoresis. Mildly increased plasma cells were found in bone
      marrow cytomorphologic examination. Renal biopsy revealed diffuse linear
      monoclonal IgA-kappa light chain deposits along tubular basement membranes
      (TBMs), while lambda was negative. Electron microscopy showed granular electron
      dense deposits along the outer aspect of TBMs. DIAGNOSES: The patient was
      diagnosed as FS induced osteomalacia secondary to monoclonal gammopathy of renal
      significance (MGRS) (IgA-kappa type) and LCDD. INTERVENTIONS: He was treated with
      bortezomib, supplementation by phosphate, alkali agents, and active vitamin D. He
      responded well to the treatment symptomatically. OUTCOMES: We reported a rare
      case of adult acquired FS with hypophosphatemic osteomalacia secondary to LCDD
      associated with MGRS and the patient was successfully treated with bortezomib.
      LESSONS: Although few cases of LCDD with isolated symptoms of tubulointerstitial
      nephropathy, rather than glomerular symptoms have been reported. It still needs
      to be recognized as a differential diagnosis in monoclonal gammopathy.

PMID- 30200083
TI  - Effect of covered self-expanding metal stents compared with multiple plastic
      stents on benign biliary stricture: A meta-analysis.
AB  - BACKGROUND: Endoscopic placement of multiple plastic stents (MPS) has been the
      first-line treatment for benign biliary stricture (BBS). Covered self-expanding
      metal stents (cSEMS) have been used in treatment of BBS; however, the efficacy
      has not been verified. Therefore, we conducted this meta-analysis according to
      PRISMA guidelines. METHODS: PubMed, Embase, and the Cochrane Library were
      electronically and manually searched for studies published between January 1,
      1990 and April 12, 2017. Of 153 studies screened, 90 were excluded because of
      duplications. After scanning the title or abstract, only 24 studies were eligible
      for review and 6 were finally included. The investigators selected publications
      according to inclusion and exclusion criteria, processed the data, and assessed
      the quality of the selected studies. The primary endpoint outcome was stricture
      resolution, and the secondary endpoint outcomes included stricture recurrence
      rate, the number of endoscopic retrograde cholangiopancreatography (ERCP)
      sessions, and stent migration. RESULTS: A total of 6 randomized controlled trials
      with 330 participants were included in the current meta-analysis. There was no
      significant difference in stricture resolution between the cSEMS and MPS groups
      (odds ratio [OR] = 1.05, 95% confidence interval [CI] = 0.53-2.07, I = 29%, P =
      .23, Z = 0.13, P = .90). Similarly, the stricture recurrence rates (OR = 1.39,
      95% CI = 0.69-2.81, I = 38%, P = .17, Z = 0.91, P = .36) were comparable between
      cSEMS and MPS groups. Stent migration rates (OR = 1.71, 95% CI = 0.84-3.50, I =
      4%, P = .241, Z = 1.47, P = .14) were similar between cSEMS and MPS groups. There
      were fewer ERCP sessions in the cSEMS group than in the MPS group. CONCLUSIONS:
      This meta-analysis showed that cSEMS were comparable to MPS in achieving
      resolution of BBSs with fewer ERCP procedures.

PMID- 30200084
TI  - Plate fixation through an anterior approach for coronoid process fractures: A
      retrospective case series and a literature review.
AB  - Coronoid process fractures of the ulna are difficult to treat, and are associated
      with stiffness, recurrent instability, and pain. Hence, treatment of coronoid
      process fractures are challenging for surgeons. The purpose of this study was to
      report the clinical outcomes of an anterior surgical approach associated with
      plate fixation for Regan and Morrey type II or type III fractures of the coronoid
      process.We evaluated 16 consecutive patients who underwent surgical treatment for
      fracture of the coronoid process of the ulna from March 2012 to July 2016. Ten
      patients had a type II fracture, and 6 patients had a type III fracture. All
      patients underwent surgical treatment for coronoid process fracture through an
      anterior approach. While preserving the neurovascular structure, all fractures
      were treated with buttress plate fixation, maintaining the gap between brachial
      artery and median nerve. Each patient was treated with concentric reduction of
      both the ulnotrochlear and the radiocapitellar articulations, without any
      evidence of elbow instability, except 1 case, who showed some medial
      instability.At the final follow-up, solid osseous union was confirmed for all
      coronoid fractures. The average time to radiologic union was 16.3 weeks. The mean
      flexion-extension arc was 124.25 +/- 12.12 degree, with a mean flexion
      contracture of 8.25 +/- 4.36 degree, and further flexion of 132.5 +/- 9.31
      degree. The mean forearm rotation arc was 167.81 +/- 10.49 degree. Fifteen
      patients achieved a functional arc of motion. The mean Mayo elbow performance
      score was 92.1 points, with 12 excellent cases and 4 good cases.Coronoid process
      fractures of the ulna can be treated successfully with plate fixation through an
      anterior surgical approach, which allows for accurate reduction and rigid
      internal fixation and early functional exercise, resulting in a reasonable
      outcome.

PMID- 30200085
TI  - Differences in prevalence of asthma-COPD overlap according to different criteria.
AB  - Asthma and chronic obstructive pulmonary disease (COPD) are common chronic airway
      diseases. Overlap in the clinical features of these 2 diseases is observed in
      many cases, and thus, the concept of asthma-COPD overlap (ACO) has recently been
      proposed. However, the definition of ACO and the clinical significance remains to
      be determined.We evaluated the prevalence and risk of acute exacerbation in ACO
      among Korean COPD patients as defined by modified Spanish criteria and American
      Thoracic Society (ATS) Roundtable criteria.The prevalence of ACO was 47.7%
      (660/1383) by modified Spanish criteria and 1.9% (26/1383) by ATS Roundtable
      criteria. ACO, regardless of criteria, did not significant affect the
      exacerbation risk during at least 1-year follow-up period.Substantial
      discrepancies were found in the prevalence and outcome of ACO according to
      different diagnostic criteria, which would compromise implementation of ACO
      before the definition is established.

PMID- 30200086
TI  - Efficacy of Internet-delivered cognitive-behavioral therapy for the management of
      chronic pain in children and adolescents: A systematic review and meta-analysis.
AB  - BACKGROUND: Pediatric chronic pain is relatively common in the world. Although
      cognitive behavior therapy (CBT) has been shown to be efficacious in children and
      adolescents, it is generally recognized that availability and accessibility of
      CBT are limited. While Internet-delivered cognitive-behavioral therapy (ICBT)
      performs better in these areas. OBJECTIVES: This systematic review aims to
      evaluate the clinical effects of ICBT for chronic pain in youth when compared
      with the control treatments. METHODS: We searched electronic databases to
      identify randomized controlled trials that compared ICBT with the control therapy
      for pediatric chronic pain. The primary outcomes were 95% confidence intervals
      and mean difference or standardized mean difference in change of pain intensity
      and activity limitations. RESULTS: Four trials met the inclusion criteria with a
      total of 404 participants of whom 208 received ICBT. Compared with pretreatment,
      children reported significant, medium to large benefits on pain intensity,
      activity limitations, and parental protective behaviors after receiving ICBT
      immediately. Significant small to medium effects were found for outcomes of
      depressive symptoms, anxiety, and sleep quality from baseline to post-treatment
      in the ICBT group. But most measures of ICBT did not show statistically
      significant superiority to those of the control conditions, except parental
      protective behaviors. Generally children and their parents were highly acceptable
      and satisfied with ICBT. CONCLUSION: ICBT for physical and psychological
      conditions in youth with chronic pain is a full potential therapy; it can be
      successful on clinically effects and socioeconomic benefits. However, only
      limited data supported the conclusion, we require further methodologically robust
      trials. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017069811.

PMID- 30200087
TI  - Population HIV transmission risk for serodiscordant couples in Guangxi, Southern
      China: A cohort study.
AB  - We evaluated the risk of human immunodeficiency virus (HIV) transmission among
      serodiscordant couples with low adherence to antiretroviral therapy (ART).Data of
      heterosexual couples/partners in 2010 were extracted from an Internet-based
      system. Participants were then followed over the course of a year with 6- and 12
      month assessments. Prevalence and density of HIV seroconversion were calculated
      for spouses/partners who did not have a positive HIV test results at baseline. We
      calculated the transmission odds ratio (OR) value stratified by personal
      characteristics and behavioral correlates at 6- and 12-month follow-up, as well
      as seroconversion in spouses/partners over the year.A total of 5544 HIV/AIDS
      patients and their spouses/partners were recruited in this cohort. Incidence of
      HIV seroconversion among HIV-negative spouse/partner was 63.7/100 person years
      (PYs) (430/674.9) at the 6-month follow-up and 33.2/100PYs (567/1707.1PYs) at 12
      months. The OR value of transmission from female to male was 2.1 times higher
      than from male to females at 6 months and 2.3 times higher at 12 months (P <
      .001). The 55- to 64-year age group was most likely to transmit HIV to their
      spouses/partners, 2.2 times greater than the participants who were 65 years and
      older. Married participants were 2.4 times higher at 6 months and 2.5 times
      higher at 12 months to transmit HIV than divorced/widowed participants. Lastly,
      transmission among illiterate participants was 6.7 times higher at 6 months and
      2.3 times higher at 12 months than those with an educational attainment of
      community college or above.High HIV seroconversion was observed in this cohort.
      Spouses/partners who were male had the highest risk of HIV acquisition; those
      aged 55 to 64 years, having married status, and are HIV-positive with less
      education were more likely to transmit HIV.

PMID- 30200088
TI  - Effects of transcutaneous electrical nerve stimulation via peroneal nerve or
      soleus muscle on venous flow: A randomized cross-over study in healthy subjects.
AB  - BACKGROUND: Transcutaneous electrical nerve stimulation (TENS) is used to prevent
      venous stasis and thromboembolism. However, best electrostimulation parameters
      have yet to be established. The aim of the study was to compare the hemodynamic
      effects and the participants' relative discomfort of 3 TENS sequences at the
      maximum tolerated intensity stimulus. METHODS: Twenty-four healthy university
      students (50% male) participated in a cross-over, randomized study. Each
      participant received 2 TENS sequences on peroneal nerve at 1 and 5 Hz, and the
      third one on soleus muscle at 5 Hz. Popliteal flow volume (FV) and peak velocity
      (PV) were measured using Doppler ultrasound and the relative change from basal
      values was recorded. Discomfort questionnaires -visual analogue scale (VAS) and
      verbal rating scale (VRS)- were also administered to compare sensations among the
      three applications. RESULTS: All interventions produced significant hemodynamic
      responses compared to baseline. Both 5 Hz applications obtained higher FV
      increments than 1 Hz TENS (P < .001). The muscle application resulted in the
      lowest PV increment (P < .001). TENS at 5 Hz on nerve location was the worst
      tolerated, with higher values in VRS (P = .056) and VAS (P = .11), although not
      significant. CONCLUSION: TENS at 5 Hz on soleus site may be the most appropriate
      protocol for enhancing venous return.

PMID- 30200089
TI  - Comparison of the UEScope videolaryngoscope with the Macintosh laryngoscope
      during simulated cardiopulmonary resuscitation: A randomized, cross-over, multi
      center manikin study.
AB  - BACKGROUND: Endotracheal intubation (ETI) can be challenging, especially in life
      threatening situations such as cardiopulmonary resuscitation (CPR).
      Videolaryngoscopes aim to ease ETI, but effort is still widely discussed. This
      study intended to investigate 2 different airway devices regarding the success
      rate of ETI during ongoing chest compressions. METHODS: This randomized, cross
      over, multi-center manikin trial included 85 experienced paramedics actively
      working in the emergency medicine service. After a standardized training session,
      all paramedics underwent 3 airway scenarios using both, direct laryngoscopy using
      a Macintosh blade and videolaryngoscope (the UEScope): normal airway without
      chest compressions, normal airway with uninterrupted chest compressions, and
      difficult airway with uninterrupted chest compressions. The primary outcome was
      successful ETI, defined as successful placement of the endotracheal tube within
      the manikin's trachea. Secondary outcomes were number of intubation attempts,
      time to successful ETI, time to best glottis view, best percent of glottic
      opening, best glottic view score (Cormack and Lehane), occurrence of dental
      trauma, ease of use, and willing to reuse in real-life situations. RESULTS: The
      UEScope provided a better glottis visualization, and higher first pass intubation
      success rate compared to direct laryngoscopy in all 3 scenarios. The overall
      intubation success was higher, and the intubation time was shorter with the
      UEScope in scenario B and scenario C, but was comparable in scenario A. Dental
      compression occurred less often using the UEScope and paramedics rated intubation
      using the UEScope easier compared to direct laryngoscopy in all 3 airway
      scenarios. CONCLUSION: In simulated CPR scenarios, intubation with the UEScope
      resulted in a better glottis visualization, a higher intubation success, and a
      shorter intubation time compared to Macintosh laryngoscope (MAC). Moreover, in
      situations where the airway is difficult for ETI especially by the paramedic, the
      UEScope would be a better choice than the MAC. Further studies are needed to
      confirm these results in real-life patients.

PMID- 30200090
TI  - Association between serum uric acid and arterial stiffness in a low-risk, middle
      aged, large Korean population: A cross-sectional study.
AB  - We investigated the association between serum uric acid (SUA) and brachial ankle
      pulse wave velocity (baPWV) in an apparently healthy population. We performed a
      cross-sectional study on middle-aged Koreans who completed a yearly health
      screening program between January and December 2014. Subjects with coronary
      artery disease, diabetes, or hypertension were excluded. Linear regression
      analyses were used to study the relationship between SUA and baPWV. Multiple
      adjustments were made for variables based on clinical or statistical
      significance. Of 66,917 study participants (38,170 men and 28,747 women), the
      mean age was 39.4 +/- 6.7 years and the average SUA level was 5.23 +/- 1.4 mg/dL.
      SUA values were higher in men than in women (6.1 +/- 1.2 mg/dL vs. 4.1 +/- 0.8
      mg/dL). SUA was linearly associated with baPWV in women and in men (P < .001,
      respectively). Multiple regression analyses remained significant for women with a
      positive association with baPWV across SUA quintiles in a dose-response manner (P
      < .001) while no longer for men with a J-shaped association between SUA quintiles
      and baPWV. When SUA modeled continuously, baPWV rose by 12.413 cm/s in women (P <
      .001) and by 6.588 cm/s in men (P < .001) for each 1 mg/dL increase of SUA. In a
      low-risk, middle-aged, large Korean population, higher SUA levels could have an
      unfavorable impact on arterial stiffness as measured by baPWV, and this
      association was stronger in women than in men.

PMID- 30200091
TI  - Study on syndrome differentiation and treatment in the management of chronic
      stable coronary artery disease to improve quality of life.
AB  - BACKGROUND: Chronic stable coronary artery disease (SCAD) is a general term for
      all kinds of coronary artery disease (CAD), which includes patients with chronic
      stable angina, old myocardial infarctions, and also stable condition after
      revascularization (i.e., percutaneous coronary intervention, coronary artery
      bypass graft). According to 2012 AHA/ACC guidelines, the objective of the
      treatment for SCAD is to maintain or recover patients' exercise tolerance,
      quality of life, and avoid complication like heart failure, so as to decrease
      mortality, eliminate symptoms, and avoid adverse reactions. Traditional Chinese
      medicine (TCM) has 2000 years of history in managing CAD and has its advantages
      in improving quality of life. Using scientific method to evaluate, demonstrate,
      and conclude the clinical curative effect of TCM is an extremely important task
      for both TCM and integrative Chinese and Western medicine in the treatment of
      CAD. METHODS: This research is to collect real effective cases from authoritative
      TCM cardiologists' clinic, so as to build a TCM diagnosis and treatment
      information database that involve 2000 patients from 32 different top-3 hospitals
      of china. The primary outcome includes EuroQol-5 Dimensions and Four diagnostic
      method of TCM, and secondary outcome includes angina score and some laboratory
      indexes like electrocardiograms, dynamic electrocardiogram, ultrasonic
      cardiogram, and treadmill exercise testing. This research uses SPSS17.0. to do
      the statistical analysis application. Enumeration data use chi test and
      measurement data which fit normality test use t test. The analysis of drugs usage
      in different diseases, different syndromes and different life quality effect will
      use principal component analysis, factorial analysis, clustering analysis. and
      point mutual information method, and so on. RESULTS: This research, based on past
      syndromes research and real clinical effective chronic SCAD cases, aim to build a
      TCM diagnosis and treatment information database.

PMID- 30200092
TI  - Preoperative oral thyroid hormones to prevent euthyroid sick syndrome and
      attenuate myocardial ischemia-reperfusion injury after cardiac surgery with
      cardiopulmonary bypass in children: A randomized, double-blind, placebo
      controlled trial.
AB  - BACKGROUND: Both euthyroid sick syndrome and myocardial ischemia-reperfusion
      injury are common and have been significantly associated with morbidity and
      mortality after pediatric cardiac surgery with cardiopulmonary bypass. This
      single-center, prospective, double-blind, randomized placebo-controlled clinical
      pilot trial was designed to assess if preoperative oral thyroid hormone therapy
      could prevent the occurrence of euthyroid sick syndrome (ESS) and attenuate
      myocardial ischemia-reperfusion injury (IRI) after cardiac surgery with
      cardiopulmonary bypass (CPB) in children. METHODS: Forty children aged 3 to 12
      year, scheduled for elective congenital heart disease repair surgery with CPB,
      were randomized into 2 groups of equal size to receive the following treatments
      in a double-blind manner: placebo (control group) and thyroid tablet 0.4 mg/kg
      (trial group) taken orally once a day for 4 days before surgery. The
      perioperative serum thyroid hormone levels and hemodynamic variables were
      determined. The extubation time, duration of intensive care unit (ICU) stay, and
      use of inotropic drugs in the ICU were recorded. The myocardial expressions of
      heat shock protein 70 (HSP70), myosin heavy chain (MHC) mRNA, and thyroid hormone
      receptor (TR) mRNA were detected. The serum creatine kinase-MB (CK-MB) activity
      and troponin I (TnI) positive ratio at 24 hour after surgery were assessed.
      RESULTS: There were no significant differences in hemodynamic variables at all
      observed points, extubation time, and duration of ICU stay between groups. As
      compared with baselines on administration, serum triiodothyronine (T3) and free
      T3 (FT3) levels on the first, second, and fourth postoperative day, and serum
      thyrotropic-stimulating hormone (TSH), tetraiodothyronine (T4), and free T4 (FT4)
      levels on the first postoperative day were significantly decreased in the 2
      groups. Serum T3, FT3, and T4 levels on the first and second postoperative day,
      and serum FT4 level on the first postoperative day were significantly higher in
      the trial group than in control group. As compared with the control group, the
      number of patients requiring inotropic drugs in the ICU, serum CK-MB activity,
      serum positive TnI ratio, and myocardial expression of MHCbeta mRNA were
      significantly decreased, and myocardial expressions of both HSP70 and MHCalpha
      mRNA were significantly increased in the trial group. CONCLUSIONS: In children
      undergoing cardiac surgery with CPB, preoperative oral small-dose thyroid hormone
      therapy reduces severity of postoperative ESS and provides a protection against
      myocardial IRI by increasing HSP70 and MHCalpha expression.

PMID- 30200093
TI  - Single-incision robotic cholecystectomy versus single-incision laparoscopic
      cholecystectomy: A systematic review and meta-analysis.
AB  - BACKGROUND: Single-incision laparoscopic cholecystectomy (SILC) is the result of
      the ongoing trend to minimally invasive of laparoscopy, but some surgeons thought
      that the SILC can increase the risk of bile duct injure or bile spillage, and the
      single-incision robotic cholecystectomy (SIRC) can overcome the drawbacks of
      SILC. Some articles described that the SIRC had longer operative time and more
      cost than SILC. The advantages and disadvantages of SIRC have still not been
      extensively studied. We aimed to investigate the outcomes of SIRC compared to
      SILC and evaluate the safety and feasibility of SIRC. METHODS: To find relevant
      studies, the electronic databases PubMed, MEDLINE, The Cochrane Library, and
      EMBASE were searched to seek information in English literature from 2011 to 2017.
      Studies comparing SIRC to SILC, for any indication, were included in the
      analysis. This systematic review and meta-analysis were performed with RevMan
      Version 5.3. RESULTS: Six comparative studies (n = 633 patients) were included in
      our analysis. The data showed that the SIRC and SILC had equivalent outcomes for
      operative time [mean difference (MD) = 17.32, 95% confidence interval (CI): -8.93
      43.57, P = .20], intraoperative complications [odd ratio (OR) = 0.48, 95% CI:
      0.17-1.39, P = .18], postoperative complications (OR = 0.62, 95% CI: 0.21-1.86, P
      = .39), hospital stay (MD = -0.01, 95% CI: -0.21-0.19, P = .90), readmissions
      rate (OR = 0.70, 95% CI: 0.09-5.63, P = .74), and conversion rate (OR = 0.52, 95%
      CI: 0.14-1.96, P = .33), but total cost was statistically significant (MD = 3.7,
      95% CI: 3.61-3.79, P < .00001). CONCLUSION: SIRC is a safe and feasible procedure
      for cholecystectomy, and the operative time is same as SILC, but the total cost
      of SIRC is significantly higher than SILC.

PMID- 30200094
TI  - Effects of a family-centered workshop for children with developmental delays.
AB  - This study investigated the effects of a short-term family-centered workshop for
      children with developmental delays.This study was conducted in a rehabilitation
      outpatient clinic of a teaching hospital. We recruited 30 children with
      developmental delays and their parents as the study group and 57 age- and sex
      matched children with typical development and their parents as the control group.
      The workshop was conducted for the children with developmental delays and their
      parents in the form of one 2-hour session per week for 6 weeks by health and
      education professionals by using a family-centered multidisciplinary approach.
      The Mandarin-Chinese Communicative Developmental Inventory and Peabody
      Developmental Motor Scales-Second Edition were used to assess the communication
      and motor skills of the children with developmental delays. The parent form of
      the Pediatric Outcomes Data Collection Instrument, Child Health Questionnaire,
      Pediatric Quality of Life (PedsQL) Inventory, and PedsQL Family Impact Module
      were administered to the parents of both groups.On study commencement, no
      significant differences were noted in functional performance and family impact
      between the children with developmental delays and those without delays. The
      children with developmental delays had lower health and health-related quality of
      life (HRQOL) scores than the children with typical development. Following the
      workshop, the study group exhibited significant improvements in physical health
      (94.2 vs 80.2, effect size: 1.00, P = .026), global function (94.8 vs 78.7,
      effect size: 0.88, P = .006), impact of the child's health on parental HRQOL
      (85.0 vs 70.4, effect size: 0.81, P = .043), and parental HRQOL (81.3 vs 65.0,
      effect size: 0.81, P = .015). No significant differences were recorded in
      function, health, HRQOL, or family impact between the children with developmental
      delays and those with typical development after 6 weeks.The multidisciplinary
      short-term family-centered workshop for children with developmental delays
      improved the children's physical health and global functional skills, and it
      reduced the impact of the child's health on parental HRQOL while also improving
      parental HRQOL.

PMID- 30200095
TI  - The risk factors of linezolid-induced lactic acidosis: A case report and review.
AB  - BACKGROUND: In recent years, linezolid is increasingly used in multidrug
      resistant bacteria therapy. At the same time, linezolid-induced lactic acidosis
      has been continually reported as a serious side effect. Notably, to our
      knowledge, there are limited available literatures that evaluate risk factors for
      linezolid-induced lactic acidosis, and there is no highly reliable study on the
      relationship between linezolid-induced lactic acidosis and age or gender.
      However, clinicians need relevant information to advice on the use of linezolid.
      Therefore, we report on a case of life-threatening lactic acidosis after 3 doses
      of linezolid exposure and evaluate the risk factors of linezolid-induced lactic
      acidosis. METHODS: Cases of linezolid-induced lactic acidosis reported in PubMed
      were searched. Several characteristics and data of case numbers and deaths were
      extracted for analysis. RESULTS: A total of 35 articles including 47 cases were
      included in this study. Twelve patients (25.5%) died due to linezolid-induced
      lactic acidosis. At the cut-offs of 7, 14, and 28 days, the mortalities were
      27.3%, 20%, and 27.3%. No statistically significant difference was observed
      according to age and gender. However, the proportion (27.7% and 29.8%) and
      mortality (30.8% and 35.7%) of male patients were much higher than females in
      both >=65 and <65 years old groups (proportion: 15.2% and 23.9%; mortality: 14.3%
      and 18.2%). CONCLUSION: The mortality of linezolid-induced lactic acidosis was
      relatively high. The duration of linezolid use and age might not be risk factors.
      Gender (specifically, male) might be related to the mortality of linezolid
      induced lactic acidosis.

PMID- 30200096
TI  - The prepurse-string suture technique for gastric defect after endoscopic full
      thickness resection (with video).
AB  - Endoscopic full-thickness resection (EFTR) is the main treatment for gastric
      tumors originating from the muscularis propria or gastric extra-luminal growth
      tumors. Successful closure of the gastric wall defect is a critical step during
      EFTR.The aim of this retrospective study was to evaluate the feasibility and
      safety of the endoscopic prepurse-string suture (p-EPSS) technique using an
      endoloop and several metallic clips during EFTR to close the perforation.Twenty
      five patients with gastric tumors originated from the muscularis propria or with
      gastric extra-luminal growth tumors who received EFTR were analyzed at the Renmin
      Hospital of Wuhan University from June 2016 to May 2017. Patient characteristics,
      tumor characteristics, operation time length, and postoperative complications
      were evaluated in all patients.All the 25 patients underwent a successful EFTR.
      Complete closure of gastric defects was also achieved. The mean operation time
      length was 31 +/- 14 minutes. The mean maximum size of tumor of was 1.7 +/- 1.0
      cm (range 0.5-4.5 cm). No severe postoperative complications occurred, such as
      massive bleeding, gastric leak, peritonitis, or abdominal abscess. No patient
      needed surgical intervention. Wounds were well healed 1 month after EFTR. No
      tumor metastasis and recurrence were observed during the follow-up period
      (median, 7 months).The p-EPSS technique using endoloop and several sterile
      repositionable hemostasis clips is safe and feasible for closing gastric
      perforation during EFTR.

PMID- 30200097
TI  - A quality-of-life system to evaluate children with leukemia in China.
AB  - The scale for assessing the quality of life (QOL) of children with leukemia of
      different ages is vacant in China.Items for developing a QOL scale were selected
      through a literature review, interviews with 58 parents and children with
      leukemia by Delphi method, which involved pediatric oncologists, psychologists,
      and pediatricians. The initial items were formulated through 2 rounds of the
      Delphi method and statistical analyses. The formulated scale was pre-tested for
      reliability and validity. A method was adopted to weight the importance of items
      within the evaluation index system.The final scale includes 5 dimensions. There
      are 10 secondary items for age 2 to 4 years, 12 secondary items for all other age
      groups, and 29, 46, 52, and 50 tertiary items for the age groups 2 to 4 years, 5
      to 7 years, 8 to 12 years, and 13 to 18 years, respectively. The authority
      coefficient for experts was 0.75, with Kendall's W coefficient P < .01, for both
      rounds. The entire Cronbach alpha was >0.9, and the content validity >0.75. The
      weights of the first-grade items are: 0.201, 0.203, 0.198, 0.201, and 0.198.This
      quality-of-life scale for children with leukemia in China has demonstrated
      reliability and validity, while a further validity assessment is required.

PMID- 30200098
TI  - Clinical outcomes of posterior pedicle screw instrumentation without osteotomy in
      the management of adolescent idiopathic scoliosis.
AB  - The aim of the study was to identify the effectiveness of posterior pedicle screw
      instrumentation without osteotomy in the management of adolescent idiopathic
      scoliosis (AIS).The AIS patients underwent standing anteroposterior and lateral
      radiography before and after surgery. Age, sex, Lenke type, preoperative and
      postoperative Cobb angle, and all the related complications were recorded at
      final follow-up.We investigated data from 137 AIS patients who underwent
      posterior pedicle screw instrumentation without osteotomy from January 2012 to
      January 2016 with >2 years follow-up. Mean age was 14.3 +/- 1.5 years at
      operation. The preoperative and latest postoperative coronal Cobb angle was 60 +/
      12 degrees  and 9 +/- 5 degrees , respectively. Additionally, complications were
      noted in 6 patients. However, the prognosis of all the AIS patients was good, and
      the satisfaction of the Scoliosis Research Society Outcomes Instrument (SRS-22)
      questionnaire was 4.4 +/- 0.5 at final follow-up.In the management of mild and
      moderate AIS, satisfactory clinical results can be obtained using posterior
      pedicle screw instrumentation without osteotomy.

PMID- 30200100
TI  - The quality of life and readiness of Polish nurses to take new competences of
      drug prescribing.
AB  - Satisfaction with life in the case of nurses is closely related to their
      professional work and is an important factor affecting the quality of work and
      patient care.An analysis of the readiness of Polish nurses depending on the level
      of life satisfaction.The study was conducted from January to November 2016 in
      randomly selected 13 health care facilities and 756 nurses in the South-Eastern
      part of Poland. The study used the satisfaction with life scale and the author's
      questionnaire.Nearly 75% of the nurses surveyed declared (reported) a low and
      average level of satisfaction. The level of satisfaction significantly influenced
      the readiness of nurses to administer medicines and write prescriptions. Nurses
      who had a higher level of life satisfaction were also more prepared to prescribe
      foodstuffs for particular nutritional uses (rho = 0.095, P = .0092), medical
      devices (rho = 0.117, P = .0012), potent drugs (rho = 0.138, P = .0001),
      intoxicants (rho = 0.078, P = .0311), and psychotropic drugs (rho = 0.085, P =
      .0196).Nurses who had a higher level of life satisfaction were also more prepared
      to administer medicines, especially foodstuffs for particular nutritional uses,
      medical devices, potent drugs, narcotic drugs, and psychotropic drugs.

PMID- 30200099
TI  - Ptosis in childhood: A clinical sign of several disorders: Case series reports
      and literature review.
AB  - Blepharoptosis (ptosis) is a common but often overlooked sign that may serve as a
      sign/manifestation of other conditions, ranging from a mild and purely cosmetic
      presentation to a severe and occasionally progressive disorder. Ptosis may show
      an acute onset or may manifest as a chronic disorder. Its presentation may vary:
      unilateral versus bilateral, progressive versus non-progressive, isolated versus
      complex which occurs in association with other symptoms, and congenital versus
      acquired (often concomitant with neuromuscular disorders).Congenital ptosis
      includes the isolated type-the congenital cranial dysinnervation disorders, which
      are further, distinguished into different subtypes such as Horner syndrome (HS),
      and ptosis as a sign/manifestation of various congenital malformation
      syndromes.In this article, we review the primary causes of ptosis occurring in
      childhood, and its various clinical presentations, including a short report on
      selected cases observed in our institution: a classical isolated familial ptosis
      comprising 14 members over 5 generations, 3 sibling with isolated congenital
      ptosis who in addition suffered by episodes of febrile seizures, a patient with
      Duane retraction syndrome who presented congenital skin and hair anomalies, and a
      girl with HS who showed a history of congenital imperforate hymen. A flowchart
      outlining the congenital and acquired type of ptosis and the clinical approach to
      the management and treatment of children with this anomaly is reported.

PMID- 30200101
TI  - Hope as a behavior and cognitive process: A new clinical strategy about mental
      health's prevention.
AB  - INTRODUCTION: Given the aging population, it is necessary to develop strategies
      for the prevention and promotion of mental health in the elderly. Hope as the
      ability to trace and maintain paths can be used as a key construct for these
      strategies, promoting cognitive health if stimulated. OBJECTIVE: Evaluate the
      behavior and cognitive development of elderly people through hope training as a
      clinical strategy for health promotion. METHODS: A clinical experiment with a
      comparative and cross-sectional design. There were 2 data collection phases over
      a 6-month period. The sample comprised 51 participants, divided into groups
      having received either more or less than 6 months of stimulation. The instruments
      used were the Mini-Mental State Examination (MMSE), Geriatric Depression Scale
      (GDS), and Expectations/Hope Scale About the Future and Life's Guidance. The
      Wilcoxon signed-ranks test (t test) was used to analyze the data. RESULTS: Hope
      in addition to cognitive stimulation shows more significant results in elderly
      people at initial stimulation (0.18), mainly at the permanence and
      troubleshooting on the paths concerned; this corresponds with the results
      obtained for hope (0.18). Depressive symptomatology showed significant
      differences among the 2 groups (0.39 and 0.02). In the between-groups
      comparisons, only GDS showed significance (0.46).Hope training has an impact on
      the remission of depressive symptoms and, despite increased hope levels, training
      was effective for the reduction of depression symptoms for up to 6 months,
      thereafter only playing a maintenance role. Broadly, hope has been shown to
      promote elderly people's mental health.

PMID- 30200102
TI  - LncRNA TUG1 promotes cells proliferation and inhibits cells apoptosis through
      regulating AURKA in epithelial ovarian cancer cells.
AB  - This study aimed to assess the effect of long noncoding RNAs (lncRNAs) taurine
      upregulated gene 1 (TUG1) on cells proliferation and apoptosis as well as its
      targeting genes in epithelial ovarian cancer (EOC) cells.Blank mimic, lncRNA TUG1
      mimic, blank inhibitor, and lncRNA TUG1 inhibitor plasmids were transfected into
      SK-OV-3 (SKOV3) cells. Rescue experiment was performed by the transfection of
      lncRNA TUG1 inhibitor and Aurora kinase A (AURKA) mimic plasmids into SKOV3
      cells. Cell counting kit-8 (CKK-8), annexin V-FITC (AV)-propidium iodide (PI) (AV
      PI), quantitative polymerase chain reaction (qPCR), and western blot assays were
      performed to detect cells proliferation, apoptosis, RNA expression, and protein
      expression respectively.Cells proliferation was increased in lncRNA TUG1 mimic
      group and decreased in lncRNA TUG1 inhibitor group than normal control (NC)
      groups. Cells apoptosis rate was repressed after treatment with lncRNA TUG1 mimic
      and promoted after treatment with lncRNA TUG1 inhibitor. AURKA expression but not
      CLDN3, SERPINE1, or ETS1 expression was adversely regulated by lncRNA TUG1 mimic
      and inhibitor. After transferring lncRNA TUG1 (-) and AURKA (+) plasmids, cells
      proliferation was increased, while cells apoptosis rate was decreased in AURKA
      mimic (+)/lncRNA TUG1 inhibitor (-) group than NC (+)/lncRNA TUG1 (-) group,
      which suggested lncRNA TUG1 regulated cells proliferation and cells apoptosis
      through targeting AURKA.LncRNA TUG1 promotes cells proliferation and inhibits
      cells apoptosis through regulating AURKA in EOC cells.

PMID- 30200103
TI  - Effects of sternocleidomastoid muscle and suboccipital muscle soft tissue release
      on muscle hardness and pressure pain of the sternocleidomastoid muscle and upper
      trapezius muscle in smartphone users with latent trigger points.
AB  - Few studies have been performed regarding the reduction of pain in the upper
      trapezius (UT) muscle by applying interventions to the sternocleidomastoid (SCM)
      muscle, which is innervated by the same nerves.The purpose of this study was to
      investigate the effects of soft tissue release intervention on the SCM and
      suboccipital muscles with regard to muscle hardness and pressure pain threshold
      (PPT) of the SCM and UT muscles in smartphone users with latent myofascial
      trigger points (MTrPs) in the UT muscle.Seventeen smartphone users (5 men and 12
      women) with latent MTrPs in the UT muscle participated in the study. This study
      used a single blinding, cross-over design, wherein sternocleidomastoid soft
      tissue release (SSTR) and suboccipital release (SR) were applied on the subjects
      in random order one week apart. Muscle hardness and the PPT of the SCM and UT
      muscles were assessed before and after the intervention.After SSTR was applied,
      the SCM and UT muscles showed a significant decrease in muscle hardness and a
      significant increase in PPT. After SR was applied, the UT muscle showed a
      significant decrease in muscle hardness and a significant increase in PPT. When
      comparing the amount of change between the SSTR and SR interventions, significant
      differences were found for SCM muscle hardness and PPT of the UT muscle in the
      SSTR intervention, compared with the SR intervention.Therefore, we suggest that,
      to reduce pain in the UT muscle, it may be useful to apply intervention directly
      to the UT muscle, as well as to the SCM muscle, which is innervated by the same
      nerve.

PMID- 30200104
TI  - A new navigational apparatus for fixation of acetabular posterior column
      fractures with percutaneous retrograde lagscrew: Design and application.
AB  - The purpose of this study was to analyze the feasibility and accuracy of a newly
      developed guide apparatus for the percutaneous retrograde lag screw fixation of
      posterior column of acetabular fractures. 3D pelvic models were reconstructed
      from the helical computed tomographic data of 33 adult patients using the Mimics
      10.01 software. The virtual cylindrical implants were placed along a line passing
      through the central point of the ischial tuberosity and the midpoint between the
      most prominent point of anterior superior iliac spine and that of posterior
      superior iliac spine. Some anatomical parameters were then measured, based on
      which a guide apparatus was developed, and its safety and accuracy were
      experimentally validated with pelvic and cadaveric specimens. The screws were
      successfully placed in all of the 66 hemipelves. There was a significant
      difference between the male and female groups in the AB distance (156.26 +/- 7.28
      mm and 151.38 +/- 8.11 mm), OI distance (139.53 +/- 7.56 mm and 125.15 +/- 11.17
      mm), and diameter (12.19 +/- 1.97 mm and 10.19 +/- 2.14 mm) of the virtual
      cylindrical implants. This guide apparatus was proved effective for percutaneous
      retrograde lag screw fixation of posterior column acetabular fractures by the
      experiments with the pelvic and cadaveric specimens. Screw fixation of posterior
      column fractures via OI is safe and feasible. We designed a new percutaneous
      retrograde screw fixation guide apparatus to assist internal fixation of
      posterior column acetabular fracture.

PMID- 30200105
TI  - The contribution of interleukin-8 genotypes and expression to nasopharyngeal
      cancer susceptibility in Taiwan.
AB  - The incidence rate of nasopharyngeal cancer (nasopharyngeal carcinoma [NPC]) is
      much higher in Southeast Asia than in western countries. Interleukin-8 (IL-8), a
      chemokine produced by macrophages, epithelial cells, airway smooth muscle cells,
      and endothelial cells, is an important immuno-mediator in the development and
      progression of many types of cancer. Genetic variations in IL-8 have been
      associated with the risks of NPC and other cancers. In the current study, we
      evaluated the role of IL-8 in NPC at the levels of DNA, RNA, and protein in a
      Taiwanese population. First, in a case-control study, 176 NPC patients and 352
      cancer-free controls were genotyped, and the associations of IL-8 T - 251A, C +
      781T, C + 1633T, and A + 2767T polymorphisms with NPC risk were evaluated.
      Second, the NPC tissue samples were assessed for their IL-8 mRNA and protein
      expression by real-time quantitative reverse transcription polymerase chain
      reaction (PCR) and Western blotting, respectively. Regarding the IL-8 promoter T 
      251A, the TA and AA genotypes were associated with significantly decreased risks
      of NPC compared with the wild-type TT genotype (adjusted odds ratio = 0.61 and
      0.52, 95% confidence interval = 0.47-0.93 and 0.37-0.91, P = .0415 and .0289,
      respectively). The mRNA and protein expression levels for NPC tissues revealed no
      significant associations among the 20 NPC samples with different genotypes. These
      findings suggest that IL-8 may play an important role in the carcinogenesis of
      NPC in Taiwan.

PMID- 30200106
TI  - Continuous glucose monitoring system can improve the quality of glucose control
      and glucose variability compared with point-of-care measurement in critically ill
      patients: A randomized controlled trial.
AB  - BACKGROUND: The purpose of this study was to determine whether subcutaneous
      continuous glucose monitoring systems (CGMS) could improve glucose management in
      critically ill patients compared with frequent and conventional point-of-care
      (POC) glucose measurements. METHODS: A total of 144 patients with an expected
      length of stay in the ICU of at least 72 hours and with an admission glucose or
      two random glucose values of >10.0 mmol/L within 24 hours after admission, were
      randomly assigned to the CGMS group (n = 74) or the conventional group (C group,
      n = 70). Both groups used the same insulin algorithm to reach the same glucose
      target range (8.0-10.0 mmol/L). RESULTS: Time in range (TIR, 8.0-10.0 mmol/L),
      which is our primary outcome measure, was higher in the CGMS group than in the C
      group (51.5% vs. 29.0%, P < .001). Glucose variability (coefficient of variation,
      CV; standard deviation, SD; glucose lability index, and GLI) was improved by CGMS
      (all P < .05). Mean glucose level (MGL) (9.6 vs. 10.3 mmol/L, P = .156) and the
      proportion of patients with hypoglycemia did not differ between CGMS (5.4%) and C
      (5.7%) (P = 1.000). However, duration of hypoglycemia was reduced in the CGMS
      group (15 vs. 28 minutes, P = .032). Clinical outcomes were similar between
      groups except for the fewer usage of CRRT and lower peak plasma urea nitrogen
      level in the CGMS group. CONCLUSION: The use of CGMS, compared with POC glucose
      measurement, could improve the TIR, GV and duration of hypoglycemia.

PMID- 30200107
TI  - Is percutaneous pinning needed for the treatment of displaced distal radius
      metaphyseal fractures in children?: A systematic review.
AB  - BACKGROUND: Distal radius metaphyseal (DRM) fractures are very frequent childhood
      fractures. Whether additional percutaneous pinning improves the outcome remains
      controversial. In this review, we tried to systematically evaluate the effect of
      percutaneous pinning on re-displacement, secondary reduction, radiographs,
      function, and complications in children with displaced DRM fractures. METHODS:
      PubMed, Medline, Embase, Cochrane Library, and Web of Science databases were
      explored systematically to identify randomized controlled trials (RCTs) and
      clinical controlled trials (CCTs) comparing cast immobilization alone or
      following reduction to additional percutaneous pinning in the treatment of
      pediatric displaced DRM fractures. Two reviewers independently screened eligible
      articles and extracted relevant information from each article. The methodological
      quality of eligible articles was evaluated using the Cochrane Collaboration risk
      assessment tool (RCTs) and modified Jadad scale (CCTs). RESULTS: A total of 4
      RCTs and 3 CCTs met the inclusion criteria, with a total patient count of 1144
      children. The results showed that additional percutaneous pinning significantly
      reduced the rate of re-placement (Chi-square tests, P < .001) and complications
      (Chi-square tests, P = .030). The superior results, both radiographically and
      functionally seemed to be temporary. No difference was found between the 2 groups
      after longer-term follow-up. CONCLUSIONS: This systematic review suggested that
      compared with casting following reduction, percutaneous pinning had a positive
      effect on maintaining the initial reduction and reducing fracture complication
      rate of displaced DRM fractures in children, but with no significant improvement
      in function and radiographic outcome at the long-term follow-up. We suggest
      clinicians think twice before percutaneous pinning of displaced pediatric DRM
      fractures.

PMID- 30200108
TI  - A case of a novel CACNA1G mutation from a Chinese family with SCA42: A case
      report and literature review.
AB  - RATIONALE: Spinocerebellar ataxia (SCA), a genetically inherited heterogeneous
      disorder, is characterized by gait ataxia, dysarthria, parkinsonism, choreic
      movements, dystonia, epilepsy, cognitive and psychiatric symptoms.
      Spinocerebellar ataxia-42 (SCA42), caused by heterozygous mutation in the calcium
      channel 1G (CACNA1G) gene, is a rare SCA subtype and the transmission pattern is
      autosomal dominant inheritance. PATIENT CONCERNS: We presented a novel mutation
      (c.4721T>A; p.Met1574Lys) in 3 patients from a Chinese family using whole-exome
      sequencing. All patients exhibited cerebellar ataxia and the clinical
      manifestations were similar to those that were previously reported in the French
      and Japanese families. In addition, cerebral magnetic resonance imaging (MRI)
      showed cerebellar atrophy, and the hot cross bun sign of brainstem was found in
      the proband and her sister. DIAGNOSES: The clinical features and MRI findings
      indicated the diagnosis of SCA. Taken together, the symptoms, MRI findings, as
      well as whole-exome sequencing made the diagnosis of SCA42 most likely candidate.
      INTERVENTIONS AND OUTCOMES: The patient was treated with cobamamide (1.5 mg once
      daily) for nerve nutrition and further physical therapy. At the 4-month follow-up
      visit, the patient's condition did not improve obviously. LESSONS: Recently, a
      missense mutation in CACNA1G gene (c.5144G4A; p.Arg1715His) was identified in
      French and Japanese families with SCA42. However, there has been no report of
      SCA42 or its mutant loci in Chinese patients. Our finding showed a novel mutation
      in CACNA1G gene and provided important insights into the pathogenesis of SCA42.

PMID- 30200109
TI  - Acute diffuse and transient thyroid swelling after intravenous thrombolysis for
      acute ischemic stroke: A case report.
AB  - RATIONALE: Intravenous thrombolysis is the primary therapy for acute ischemic
      stroke (AIS), but it has some complications, including symptomatic intracranial
      hemorrhage, orolingual angioedema, and extracranial bleeding. However, thyroid
      disorders associated with thrombolysis are very rare. PATIENT CONCERNS: A 56-year
      old man developed acute pain and neck swelling after thrombolysis with
      recombinant tissue plasminogen activator. DIAGNOSES: Ultrasound revealed a
      diffusely enlarged thyroid with linear hypoechoic areas throughout the entire
      gland, resembling a "cracked" appearance. INTERVENTIONS: The patient was treated
      conservatively with cold packs and observed closely. Follow-up ultrasound was
      made. OUTCOMES: A few hours later, pain and swelling disappeared completely. A
      repeat ultrasound revealed complete recovery of thyroid volume and aspect on the
      next day. LESSONS: After intravenous thrombolysis for AIS, several life
      threatening complications, such as hemorrhage and orolingual angiedema, also can
      cause neck swelling. Urgent intubation and surgery may be required. However, the
      rare complication, acute diffuse thyroid swelling, is self-limiting and nonfatal
      and conservative treatment is sufficient. Neck ultrasound is helpful in rapidly
      distinguishing these complications.

PMID- 30200110
TI  - Causes and prognosis of chronic intestinal pseudo-obstruction in 48 subjects: A
      10-year retrospective case series.
AB  - The aim of the study was to evaluate the prognosis and survival of pediatric
      subjects with chronic intestinal pseudo-obstruction (CIPO) and investigate the
      independent risk factors affecting their prognosis.This was a retrospective case
      series of all pediatric subjects suffering from CIPO and treated at the Pediatric
      Surgical ward of Xinhua Hospital between January 2006 and January 2016.The
      overall mortality was 19/48 (39.6%). Because of delayed CIPO diagnosis, many
      subjects underwent a variety of surgical procedures. The rate of additional
      surgical procedures was high (35/48, 72.9%), but the number of surgical
      procedures, parenteral nutrition, and megacystis did not affect mortality.
      Mycotic infection was significantly associated with mortality, while onset at <1
      year and hypoganglionosis showed a tendency to be associated with
      mortality.Mycotic infection was associated with mortality of children with CIPO.
      Despite improving treatment approaches, the overall prognosis of CIPO remains
      poor. The choice of the surgical intervention could be based on standard
      criteria.

PMID- 30200112
TI  - Therapeutic challenges in pregnant women with paroxysmal nocturnal
      hemoglobinuria: A case report.
AB  - INTRODUCTION: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired
      disease, arising from the mutation of clonal hematopoietic stem cells, with an
      estimated incidence of 1 to 5 cases per million individuals. In pregnant women,
      adequate information regarding the prevalence of PNH is lacking, and its
      management has been a challenge because of the significant complications in this
      group. The condition is diagnosed based on clinical findings and laboratory
      tests. Eculizumab, the drug of choice for the treatment of PNH, reduces hemolysis
      and stabilizes hemoglobin levels, thereby decreasing the need for blood
      transfusions and improving the overall quality of life. CASE PRESENTATION: A 38
      year-old woman was diagnosed with PNH in 2007 and eculizumab therapy was
      initiated at the end of 2014. She became pregnant in September 2015 and presented
      various decompensations from forced reductions in therapy due to the
      nonavailability of eculizumab. The pregnancy was interrupted in week 35, but the
      well-being of the newborn was not compromised. The patient, however, had to
      remain hospitalized for resolution of acute kidney insufficiency, anemia, and
      intense hemolysis, which were reverted by means of intravenous hydration,
      transfusion of 10 packed red blood cell units, and eculizumab therapy.
      CONCLUSION: The rarity of the disease and the lack of protocols for its
      management during pregnancy hampered the treatment of the patient. However, the
      symptoms were progressively treated as they appeared, based on laboratory tests
      since it was necessary to circumvent and handle the lack of eculizumab which was
      not readily available in Brazil's Public Health System.

PMID- 30200111
TI  - Antinatriuretic phenomena seen in children with acute pyelonephritis may be
      related to the activation of intrarenal RAAS.
AB  - We investigated whether antinatriuretic phenomena [decreases in urinary sodium
      (uNa) and fractional excretion of sodium (FENa)] seen in children with acute
      pyelonephritis (APN) are associated with the renin-angiotensin-aldosterone system
      (RAAS).We examined 114 children experiencing their first episode of febrile
      urinary tract infection (fUTI) consecutively admitted to our hospital from July
      2012 to June 2014. Blood tests [C-reactive protein, white blood cell count,
      erythrocyte sedimentation rate, and aldosterone (Aldo)] and urine tests [uNa,
      urine potassium (uK) and FENa] were performed upon admission. All enrolled
      children underwent a 99m-dimercaptosuccinic acid renal scanning (DMSA) at
      admission. Areas with cortical defects (AreaCD) and uptake counts (UptakeCD) on
      their DMSA scans were calculated. Data were compared between children with
      positive DMSA results (APN), lower urinary tract infection (L-UTI), and controls;
      and between children with high and low Aldo levels.uNa, uNa/K, and FENa
      negatively correlated with AreaCD%, UptakeCD, and Aldo; were significantly lower
      in APN patients than in LUTIs and controls regardless of Aldo level; were lower
      in the high Aldo group than in the low Aldo group. However, there is no
      difference in AreaCD% and UptakeCD between APN children with the high and low
      Aldo level.Decreases in uNa, uNa/K, and FENa in children with APN may result from
      an antinatriuretic effect of RAAS and be related to the activation of the
      intrarenal RAAS.

PMID- 30200113
TI  - Measuring the sense of self in brain-damaged patients: A STROBE-compliant
      article.
AB  - Recently, researchers have focused on the embodied sense of self (ESS), which
      consists of the minimal and narrative selves. Although a study demonstrated that
      the ESS is related to brain dysfunction empirically, the subjective aspects of
      the ESS, and a systematic approach to it, have not yet been examined in brain
      damaged patients. To examine this, we measured the ESS of patients with brain
      tumors before and after awake craniotomy.A self-reported questionnaire called the
      Embodied Sense of Self Scale (ESSS) was used to measure the ESS in patients with
      brain tumors before and after surgery. For comparison, age-matched controls also
      completed the ESSS.The ESSS scores of the patients with brain tumors before
      surgery were higher than those of the controls and improved after surgery. Before
      surgery, patients with left hemispheric lesions had a poorer ESSS than those with
      right hemispheric lesions. Episodic memory disturbance was highly correlated with
      malfunction of narrative self and ownership.Brain lesions were associated with
      anomalous ESSS, associated with hemispheric laterality and cognitive dysfunction.

PMID- 30200114
TI  - Mucin-producing hepatocellular carcinoma without morphological features of
      biliary differentiation: A case report.
AB  - RATIONALE: Hepatocellular carcinoma has been believed not to produce mucin unless
      it has biliary differentiation. However, some cases of hepatocellular carcinoma
      with extracellular myxoid change have been reported recently, raising the
      possibility that, in rare cases, hepatocellular carcinoma cells produce mucin.
      PATIENT CONCERNS: Here we report a case of hepatocellular carcinoma that
      contained intracellular and extracellular myxoid matrix without morphological
      evidence of biliary differentiation, although cells in a portion of the tumor
      were positive for the epithelial markers cytokeratin 7 and 19. She was brought to
      our hospital due to abnormal liver tests and a large liver tumor found by
      ultrasound examination. DIAGNOSES: The liver tumor showed typical imaging
      findings of hepatocellular carcinoma. INTERVENTIONS: The tumor was resected with
      negative margins, and pathologically diagnosed as hepatocellular carcinoma with
      mucin production. OUTCOMES: The patient has been free from recurrence of cancer
      during two-years' follow-up. LESSONS: Our case suggests that hepatocellular
      carcinoma cells can produce mucin without or before morphological differentiation
      to biliary phenotypes, an observation that may help elucidate the mechanism for
      the development of combined hepatocellular and cholangiocarcinoma.

PMID- 30200115
TI  - Physiolgic hypercortisolism at onset of celiac disease in a girl: A case report.
AB  - RATIONALE: Celiac disease (CD) is an autoimmune disorder induced by dietary
      gluten in genetically predisposed subjects. Activation of the hypothalamic
      pituitary-axis (HPA) can occur in patients with CD; however, this condition has
      never been described in overweight/obese CD children. PATIENT CONCERNS: A 12-year
      old girl with CD was admitted with mild acanthosis nigricans of the armpits,
      groin and neck. Recently, extra fat appeared around the neck, and moon face was
      observed. The abdomen was globular and meteoric, treatable and not aching. She
      weighed 64 kilos (75 degrees -97 degrees  percentile) and was 146 centimeters
      tall (3 degrees -25 degrees  percentile) with a body mass index of 30 kg/mq.
      Laboratory tests revealed hypertriglyceridemia and positive anti-transglutaminase
      IgA. Cortisoluria was determined. Serum ACTH was normal. DIAGNOSES: This paper
      reports a case of a girl with CD in which both obesity and activation of HPA
      activity were noted. INTERVENTIONS: During follow-up, anti-transglutaminase IgA
      increased to 201.5 UI/mL. The patient was positive for anti-endomysium
      antibodies, and the HLA DQ2 haplotype was identified, confirming a diagnosis of
      CD. OUTCOMES: Despite a gluten-free diet, obesity and hyperadrenalism persisted,
      and anti-transglutaminase antibodies remained elevated. In addition, high
      cortisoluria persisted. A high-dose suppression dexamethasone test (8 mg)
      produced negative results with a morning cortisol value of 1 ng/mL, suggesting
      the diagnosis of pseudo-Cushing's syndrome. LESSONS: This case highlights that
      the first manifestation of CD could be being overweight, and this finding seems
      to support the need to prescribe laboratory tests for CD not only to children
      with failure to thrive, as commonly recommended, but also to those with increased
      body weight.

PMID- 30200116
TI  - Conservative treatment of a pathologic fracture of the scaphoid bone in a child:
      A case report.
AB  - RATIONALE: Tumors of the scaphoid are rare, and some can cause pathological
      fractures. No cases of pathological fractures of the scaphoid have been reported
      in children. The most common treatment for pathologic fractures of the scaphoid
      bone associated with a benign lesion in adults is surgical, with intralesional
      curettage associated with autologous bone grafting and internal fixation. PATIENT
      CONCERNS: A 10-year-old boy presented with wrist pain after falling from his
      height. DIAGNOSES: X-ray, CT-scan and MRI showed a pathological undisplaced
      fracture of the scaphoid on a benign lytic lesion. INTERVENTIONS: The arm was
      immobilized in a below-elbow cast. OUTCOMES: The fracture healed within 4 months
      of immobilization. 3 years after the fracture, the functional status was normal,
      and the lytic lesion could not be seen on radiographs. LESSONS: Retrospectively,
      the most probable etiology was a ganglion cyst. Our case suggests that some
      pathological fractures of the scaphoid may not need surgery, especially not in
      children.

PMID- 30200117
TI  - Secondary basal cell carcinoma of scalp after radiotherapy: A case report.
AB  - RATIONALE: Radiotherapy (RT) is widely used for both malignant and benign tumors
      in order to reduce the risk of recurrence, to promote tumor control, and to
      improve survival. However, there have been studies reported that RT is also a
      risk factor of secondary cancer. Very few cases of secondary malignancy after RT
      to high grade brain cancer have been reported due to short survival of this
      disease, and most RT-induced malignancies presented with sarcomatous histology.
      Here we present a patient with basal cell carcinoma (BCC) 14 years after RT to
      his brain. PATIENT CONCERNS: A 28-year-old man without any underlying disease had
      suffered from left side weakness and clonic-tonic seizures for 12 days.
      DIAGNOSES: His brain images showed a tumor in the right frontal lobe. The
      pathologic report confirmed anaplastic astrocytoma (WHO Grade III).
      INTERVENTIONS: After craniotomy and tumor biopsy, RT was delivered. Fourteen
      years later, a gray-colored skin papule was noted in the previously irradiated
      area. The scalp biopsy revealed BCC. The scalp BCC was adequately resected. He
      then suffered from brain tumor recurrence and received further craniotomy for
      three times combined with chemotherapy with temozolomide. OUTCOMES: After
      treatment, follow-up brain images showed that the disease was under control.
      There was no neurological sequela. For scalp BCC, no skin tumor recurrence has
      been noted to date after the resection 14 years after initial RT. He has survived
      for more than 26 years since his initial diagnosis of anaplastic astrocytoma, and
      more than 12 years from the diagnosis of scalp BCC. LESSONS: Notwithstanding the
      risk of radiation-induced skin cancer, RT contributed to this patient's survival.
      The possible late adverse events should be informed to the patients.

PMID- 30200118
TI  - A more physiological feeding process in ICU: Intermittent infusion with semi
      solid nutrients (CONSORT-compliant).
AB  - INTRODUCTION AND OBJECTIVES: The goal of this study is to determine whether the
      application of semi-solid nutrients could increase the efficiency of the enteral
      nutrition (EN), which was measured daily by administered volume of
      nutrition/prescribed volume of nutrition. METHODS: A total of 28 subjects were
      finally enrolled in the study and randomized to receive either intermittent
      feeding (IF) or intermittent feeding with semi-solid nutrients (IS). Three major
      parameters concerning EN were evaluated in this study: the daily dosage
      prescribed by doctor, the actual dosage received by subjects, and the acute
      complications such as diarrhea, vomiting, regurgitation, bowel distension, and
      lung infection. RESULTS: There were no statistical differences in NRS-2002, and
      acute gastrointestinal injury between both groups. The IS group (0.98 +/- 0.06, P
      < .01) could receive higher percentage of daily prescribed calories compared to
      IF (0.73 +/- 0.15). The total caloric intake during the first 3 days was higher
      in IS (2589.29 +/- 844.02 vs. 1685.71 +/- 388.00, P < .01). The incidence of
      feeding intolerance (FI) was lower in the IS group (2/14) compared with IF
      (8/14). However, semi-solid nutrients did not decrease the length of stay, lung
      infection, or 30-day mortality. Similarly, there was no difference in glycemic
      variability and stress hyperglycemia. CONCLUSIONS: In our cohort of critically
      ill subjects, the efficiency of the EN was increased by IS, which might be
      related to the improvement of FI (NCT03017079).

PMID- 30200119
TI  - Nasointestinal tubes versus nasogastric tubes in the management of small-bowel
      obstruction: A meta-analysis.
AB  - BACKGROUND: There is no consensus regarding the therapeutic effect of
      nasointestinal tubes (NITs) versus nasogastric tubes (NGTs) in the management of
      small-bowel obstruction (SBO). This study aimed to compare the clinical outcomes
      between the use of NITs and NGTs in the management of SBO. METHODS: Published
      studies on comparing NITs with NGTs in the treatment of SBO were searched from
      electronic databases. Two investigators independently extracted the data; any
      discrepancies were adjudicated by a third investigator. Pooled odds ratio (OR)
      and 95% confidence interval (CI) were calculated using Review Manager 5.0.
      RESULTS: An extensive literature search identified 268 relevant publications, 4
      of which met the inclusion criteria. There were no significant differences in the
      nonrequirement of operative intervention between NITs and NGTs groups (OR: 1.79;
      95% CI: 0.55, 5.84). Compared with the NGTs, the NITs, which successfully passed
      through the pylorus, did not decrease the rate of operation in patients with SBO
      (OR: 2.19; 95% CI: 0.59, 8.15). There was no advantage of NITs over NGTs in
      patients with partial SBO (P-SBO) (OR: 1.04; 95% CI: 0.23, 4.60). Postoperative
      complications were compared between the groups (OR: 2.13; 95% CI: 1.09, 4.15).
      CONCLUSION: The result of this meta-analysis showed no advantage of NITs over
      NGTs in the management of patients with SBO.

PMID- 30200121
TI  - Establishment of a Han Chinese-specific pharmacogenetic-guided warfarin dosing
      algorithm.
AB  - Warfarin is the most common oral anticoagulant. Because of a narrow therapeutic
      range, interindividual differences in drug responses, and the risk of bleeding,
      there are many challenges in using warfarin. We need to predict the warfarin
      maintenance dose. However, ethnic-specific algorithms may be required, and some
      Chinese algorithms do not perform adequately. Therefore, we aimed to establish a
      Han Chinese appropriate algorithm.We recruited a study group consisting of 361
      Han Chinese patients receiving warfarin treatment who had heart valve
      replacements. Genotyping of 38 single nucleotide polymorphisms (SNPs) in 13
      candidate genes was carried out using the MassARRAY. In the derivation cohort, a
      multiple linear regression model was constructed to predict the warfarin dosage.
      We evaluated the accuracy of our algorithm in the validation cohort and compared
      it with the other 5 algorithms based on Han Chinese and other races.We
      established a Han Chinese-specific pharmacogenetic-guided warfarin dosing
      algorithm. Warfarin maintenance dosage (mg/day) = 1.787 - 0.023 * (Age) + 1.151 *
      (BSA [m]) + 0.917 * (VKORC1 AG) + 4.619 * (VKORC1 GG) + 0.595 * (CYP4F2 TT) +
      0.707 * (CYP2C19 CC). It explained 58.3% of the variance in warfarin doses in Han
      Chinese patients and was superior to the other 5 algorithms. The ability of the 6
      algorithms which estimate the required dose correctly was tested. Our model had a
      mean absolute error of 0.74 mg/day, the other 5 models have mean absolute error
      of 0.81 mg/day,1.05 mg/day, 1.24 mg/day, 1.18 mg/day, and 0.85 mg/day,
      respectively. Our model had a mean percentage error of 26.9%, the other 5 models
      have the mean percentage error of 27.7%, 27.2%, 52.3%, 45.7%, and 29.3%,
      respectively.Physicians can not adopt algorithm from other race directly to
      predict warfarin dose in patients with heart valve replacements, they should
      establish a new algorithm or adjust another algorithm to fit their patients. The
      algorithm established in this study has the potential to assist physicians in
      determining warfarin doses that are close to the appropriate doses.

PMID- 30200120
TI  - Prognostic value of pretreatment neutrophil-to-lymphocyte ratio in patients with
      soft tissue sarcoma: A meta-analysis.
AB  - BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) has been reported to possess
      significant prognostic value in multiple types of cancer. We conducted a meta
      analysis to evaluate the prognostic value of pretreatment NLR in soft tissue
      sarcoma (STS). METHODS: A systematic literature search through April 2018 was
      conducted to identify studies evaluating the prognostic value of the pretreatment
      NLR in STS patients. The end points were overall survival (OS), disease-free
      survival (DFS), progression-free survival (PFS), and clinicopathological
      parameters. All statistical analyses were conducted with Stata 13.0. RESULTS:
      Fourteen cohorts with 2820 patients were analyzed. Elevated NLR was significantly
      correlated with worse OS [hazard ratio (HR): 1.59, 95% confidence interval (95%
      CI): 1.28-1.97, P < .001] and DFS/PFS (HR = 1.28; 95% CI = 1.12-1.47; P < .001).
      In addition, elevated NLR was highly correlated with age (>= 65 years), tumor
      size (>5 cm), tumor depth (deep), Grade (G3), and TNM stage (III-IV). CONCLUSION:
      Overall, pretreatment NLR could be an adverse prognostic biomarker for STS.

PMID- 30200122
TI  - Posteromedial elbow dislocation with lateral humeral condylar fracture in
      children: Three case reports and a literature review.
AB  - RATIONALE: Posteromedial dislocations of the elbow with lateral humeral condylar
      fractures (LCFs) are uncommon, and only isolated cases have been reported in the
      English-language literature. Because of the complex radiolucent cartilaginous
      structures and late-appearing ossification centers, radiological diagnosis of
      elbow dislocations with LCF in children is challenging. PATIENT CONCERNS: We
      report three children with posteromedial elbow dislocation: two patients with
      Milch type I and one patient with Milch type II LCF. DIAGNOSES: In our report,
      radiographs showed only a small bone fragment, and arthrography or computed
      tomography were helpful diagnostic aids in cases 1 and 3. In contrast, the
      patient in case 2 was initially misdiagnosed as having an epiphyseal separation
      of the distal humerus, and open reduction and internal fixation through the
      posterior approach revealed Milch type II LCF. INTERVENTIONS: In case 1 and 3,
      Milch type I LCFs, open reduction and internal fixation was performed through the
      posterolateral approach. On the other hand, in case 2, Milch type II LCF, open
      reduction and internal fixation was performed through the posterior approach.
      OUTCOMES: Poor reduction of Milch type I LCFs resulted in incongruity of the
      articular surface and poor cosmetic results in two patients. In case 2, Milch
      type II LCF, plain radiographs showed adequate healing without elbow deformity
      and the clinical result was excellent. LESSONS: Because LCFs are intra-articular
      fractures, anatomical reduction is crucial for satisfactory outcomes. We promote
      awareness of this injury, especially posteromedial dislocation with Milch type I
      LCF. Preoperative evaluation is helpful for achieving satisfactory outcomes, and
      open reduction and internal fixation through an anterolateral approach might be
      most appropriate for Milch type I LCFs.

PMID- 30200123
TI  - Titanium mesh bone grafting combined with pedicle screw internal fixation for
      treatment of Ku[Combining Diaeresis]mmell disease with cord compression: A case
      report and literature review.
AB  - RATIONALE: In 1891, Dr. Hermann Kummell, a German surgeon, described a clinical
      entity characterized by the development of progressive painful kyphosis following
      an asymptomatic period of months or years after a minor spinal trauma, leading to
      a gradual collapse of the vertebra and dynamic instability, ultimately
      progressing to kyphosis with prolonged back pain and/or paraparesis. To date, the
      main pathologic eliciting event remains unclear, and no standard treatment or
      single effective treatment are available for Kummell disease. PATIENT CONCERNS: A
      74-year-old woman presented with severe back pain and numbness of both legs for
      approximately 2 months. DIAGNOSES: According to the clinical symptoms and imaging
      examinations, the patient was diagnosed with stage III Kummell disease.
      INTERVENTIONS: The patient underwent titanium mesh bone grafting combined with
      pedicle screw internal fixation. OUTCOMES: Postoperative kyphosis was corrected,
      and the vertebra was reconstructed. LESSONS: Kummell disease is not a rare
      complication of osteoporotic vertebral compression fractures, and treatment of
      each patient must be individualized. The application of titanium mesh bone
      grafting combined with pedicle screw internal fixation is an effective treatment
      option for stage III Kummell disease.

PMID- 30200124
TI  - The association between urinary tract infection during pregnancy and
      preeclampsia: A meta-analysis.
AB  - OBJECTIVE: The association between urinary tract infection (UTI) during pregnancy
      and preeclampsia (PE) continues to be the subject of debate. This meta-analysis
      aimed to examine the relationship between UTI during pregnancy and PE. STUDY
      DESIGN: Observational studies up to October 2017, extracted from Medline, PubMed,
      Cochrane Library, and Embase databases, were included in the analysis. Data were
      extracted to 4-fold table, and the pooled odds ratio (OR) and 95% confidence
      intervals (CIs) of respective studies were calculated. Then meta-analysis was
      performed. RESULTS: Nineteen studies qualified the inclusion criteria. Urinary
      tract infection during pregnancy was found to be a risk factor for the
      development of PE (OR: 1.31, 95% CI: 1.22-1.40). CONCLUSION: Occurrence of UTI
      during pregnancy increases the risk of PE in pregnant women. Screening for, and
      treatment of UTI should be part of routine antenatal care, especially in
      developing countries.

PMID- 30200125
TI  - Outcomes of anterior approach major hepatectomy with diaphragmatic resection for
      single huge right lobe HCC with diaphragmatic invasion.
AB  - The outcomes following anterior approach (AA) hepatectomy in huge hepatocellular
      carcinoma (HCC) patients with diaphragmatic invasion (DI) remain unclear. This
      study compared the outcomes of single huge right HCC patients with and without DI
      after AA hepatectomy. A total of 203 consecutive patients with single huge right
      lobe HCC who underwent AA major hepatectomy were included. They were divided into
      group PDI (n = 53) and group ADI (n = 150) according to the presence or the
      absence of DI. Their short- and long-term outcomes were compared, and a subgroup
      analysis was performed. There were no significant differences regarding
      postoperative complications and 90-day mortality between the 2 groups. The
      overall survival (OS) and recurrence-free survival (RFS) rates were similar
      between the 2 groups. The subgroup analysis also showed that patients with tumor
      resection en bloc with part of the diaphragm had similar OS and RFS rates as
      those who underwent diaphragmatic resection after hepatectomy. Tumor diameter >=
      15 cm, serum AFP level >= 400 ng/mL, and tumor grade of G4 and microvascular
      invasion are independent predictors of poor prognosis. For the single huge right
      lobe HCC patients with DI, AA major hepatectomy combined with diaphragmatic
      resection could offer similar OS and RFS as those without diaphragmatic invasion.

PMID- 30200126
TI  - Chinese herbal medicine formulas as adjuvant therapy for osteonecrosis of the
      femoral head: A systematic review and meta-analysis of randomized controlled
      trials.
AB  - BACKGROUND: Osteonecrosis of femoral head (ONFH) is a disabling clinical entity
      affecting mainly young adults. Although Chinese Herbal Medicine (CHM) has been
      widely used as an adjunct therapy for ONFH in China, its effectiveness is not
      well defined. The purpose of this systematic review is to assess the
      effectiveness of CHM as an adjunct therapy to core decompression (CD) for
      patients with ONFH. METHODS: A systematic literature search was conducted in 10
      electronic databases. Randomized controlled trials involving CHM and CD for ONFH
      were included. Two authors independently assessed the studies for inclusion and
      extracted the data. A meta-analysis was conducted to estimate the safety and
      efficacy of CHM as an adjunct therapy. RESULTS: Twenty-three randomized
      controlled trials with 1815 participants were included. The formulas used in
      these studies were different and we only combined data of studies observing the
      same formulas. Patients treated with CHM additionally exhibited a better TER
      (total effective rate) compared with CD alone in different degree, with the risk
      ratio (RR) varies from 1.09 to 1.09. The Harris score and radiographic effective
      rate indicate a similar result, with the medicine (MD) varies from 17.35 to 14.94
      and RR 1.40 to 1.27. The risk of side-effect was barely reported except only 2
      study record that no complications were observed. CONCLUSION: This systematic
      review indicated that CHM as adjunctive therapy may improve the effectiveness of
      CD. However, a firm conclusion could not be reached because of overall high risk
      of bias in most domains. Further studies of higher quality are required, and
      other benefits of CHM remain to be determined.

PMID- 30200127
TI  - Effectiveness of the computerized balance rehabilitation after hip fracture
      surgery: A study protocol of a prospective and open-label clinical trial.
AB  - INTRODUCTION: Although balance problems in older populations are directly
      correlated with hip fractures, the overall physical gain afforded by balance
      rehabilitation itself has not yet been fully investigated. Here we describe a
      protocol for an open-label clinical trial to evaluate the effectiveness of
      computer-based balance-specific exercise (BSE) on the performance and balance of
      elderly women who underwent hip fracture surgery (HFS). METHODS AND ANALYSIS:
      Elderly female patients (>=65 years old) who underwent surgery for femoral neck,
      intertrochanteric, or subtrochanteric fracture regardless of surgery type will be
      included. The BSE will be conducted using a computed posturographic system for a
      2-week intervention period following HFS. The primary outcome of this study is
      Berg balance scale score. All functional outcomes will be measured at 1 and 3
      weeks and at 3 and 6 months after the surgical intervention. The data will be
      analyzed using the intention-to-treat principle.

PMID- 30200128
TI  - Oriental herbal medicine for insomnia in the elderly with hypertension: A
      systematic review protocol.
AB  - BACKGROUND: Hypertension and insomnia are common diseases in the elderly.
      Oriental herbal medicine has been widely used in East Asia, and it has been
      considered as a promising alternative to conventional pharmacotherapy because of
      its efficacy in geriatrics. Moreover, since oriental herbal medicine acts on
      multiple targets, it may affect both hypertension and insomnia at the same time,
      which can reduce the risk of polypharmacy in this population. This systematic
      review will assess the efficacy and safety of oriental herbal medicine in the
      elderly with both insomnia and hypertension. METHODS: Thirteen databases
      including English, Chinese, Korean, and Japanese databases will be searched from
      their inception to August 2018. We will include randomized controlled trials
      assessing oriental herbal medicine for insomnia in the elderly with hypertension.
      The methodological quality of the included studies will be evaluated using the
      Cochrane Collaboration's risk of bias tool, and confidence in the cumulative
      evidence will be evaluated using the Grading of Recommendations Assessment,
      Development, and Evaluation instrument. RESULTS: This review will provide
      evidence to determine the efficacy and safety of oriental herbal medicine in the
      elderly with both insomnia and hypertension. CONCLUSIONS: Our results will help
      clinicians and health policy makers take informed decisions regarding the use of
      oriental herbal medicine in the elderly. It will also provide evidence-based
      oriental herbal medicine data for elderly patients suffering from multiple
      diseases and their families.

PMID- 30200129
TI  - Survival benefits of oral anticoagulants in patients with pulmonary arterial
      hypertension: Protocol for a systematic review and meta-analysis.
AB  - BACKGROUND: Pulmonary arterial hypertension (PAH) is an incurable disease with
      high mortality. Although most studies recommend anticoagulation treatment for
      idiopathic pulmonary arterial hypertension (IPAH), the survival benefits are
      uncertain. Therefore, the present paper provides a protocol to investigate this
      issue by a meta-analysis. METHODS: An electronic search will be performed for
      randomized controlled trials (RCTs) or cohort studies that reported the
      interested efficacy data (pulmonary arterial pressure and survival advantage) in
      anticoagulants-treated patients with PAH. Hazard ratios with their confidence
      intervals will be calculated using a fixed- or random-effects model. RESULTS:
      This study will provide the survival benefits of anticoagulants in PAH patients
      by pooling the results of individual studies. CONCLUSION: The results will bring
      about vigorous evidence in this issue and guide both clinical decision-making and
      future research.

PMID- 30200130
TI  - Relationship between CT activity score with lung function and the serum
      angiotensin converting enzyme in pulmonary sarcoidosis on chest HRCT.
AB  - To address the reliability of CT activity score (CTAS) and investigate the
      relationships between CTAS, lung function changes after treatment and the serum
      angiotensin-converting enzyme (SACE) levels.Fifty-seven sarcoidosis patients
      underwent chest high-resolution CT (HRCT) and spirometry, as well as SACE
      examination, were retrospectively analyzed. Follow-up spirometry in each patient
      was obtained about 6 months after the initial spirometry. The correlations
      between CTAS and pulmonary function changes were evaluated by Spearman
      correlation analysis. According to SACE status, patients were divided into normal
      and high level 2 subgroups. Comparisons of pulmonary function parameters, HRCT
      abnormalities extent scores between SACE normal and high 2 subgroups were
      performed with the Mann-Whitney U test or Independent samples t test.CTAS
      demonstrated significant correlations with lung function changes (Delta%VC: rho=
      0.543, P < .001; DeltaFEV1.0/FVC:rho = 0.417, P = .001; Delta%TLC: rho = 0.309, P
      = .019). In addition, worse initial lung function, larger changes of lung
      function, and higher extent scores of HRCT were observed in SACE high-level
      subgroup.The findings of this study suggest that CTAS of initial HRCT is a
      promising index for disease activity in pulmonary sarcoidosis to some degree.
      Prospective studies with large cohort designed to address further verification
      are warranted before wide clinical practice.

PMID- 30200131
TI  - Clival chordoma: long-term clinical outcome in a single center.
AB  - The treatment of clival chordoma remains highly challenging. This difficulty is
      enhanced by the very small likelihood of a successful complete surgical resection
      or nonsurgical treatment of chordoma. Additionally, no effective means of
      interdisciplinary treatment for chordoma have been identified. With this
      background, we analyzed data of patients who underwent multidisciplinary
      treatment for clival chordoma at our institution during the last 25 years.This
      retrospective study evaluated patients treated at a single center from 1992 to
      2017.During the study period, 24 patients underwent 24 surgeries. Twenty-two
      surgical resections (including 1 initial surgery and 1 surgery for recurrence)
      were deemed maximally safe cyto-reductive resections (92%); the remaining 2
      surgeries were deemed incomplete (8%), which were histologically confirmed in all
      but in 1 case (which involved radionecrosis). The complications were divided into
      endocrinologic, neurologic, and other complications. In 1 case (4%), surgery led
      to immediate dyspnea followed by death on the following day; in another case
      (4%), ischemic infarction led to sudden death. In 3 cases (13%), patients
      exhibited improvements of neurologic (visual or oculomotor) deficits that had
      been observed prior to surgery. The following new postoperative neurologic
      deficits were observed: oculomotor deficits in 4 cases, dizziness in 2 cases, and
      cranial nerve-attributed dysphagia in 3 cases. About 19 patients underwent
      adjuvant postoperative radiotherapy following the initial surgery (dose: 54.5 Gy
      in all cases). The mean and median follow-up durations were 50 +/- 53 and 48.5
      months, respectively. A Kaplan-Meier analysis estimated a median survival
      duration of 50.2 months (95% confidence interval 27.9-72.4 months).These findings
      highlight the importance of interdisciplinary treatment strategies, particularly
      those combining maximally safe cyto-reductive tumor resection and adjusted
      radiotherapy and other treatment options, for patients with relatively good
      conditions.

PMID- 30200132
TI  - Docetaxel-induced radiation recall dermatitis with atypical features: A case
      report.
AB  - INTRODUCTION: Radiation recall dermatitis (RRD) associated with actinomycin D was
      first described by in 1959, followed by the reporting of several RRD-inducing
      drugs. In 1994, a study demonstrated docetaxel-induced RRD for the first time;
      however, despite some case studies reporting RRD, a little has been reported on
      it since then. Here we present a rare case of atypical docetaxel-induced RRD.
      CASE PRESENTATION: The patient in his 60s was administered radiotherapy for high
      risk prostate cancer. He continued receiving hormonal therapy for 2 years because
      of being in a high-risk group and became nadir. Six months since the completion
      of hormonal therapy, his prostate-specific antigen (PSA) level increased again.
      Based on the radiological examination, he was diagnosed with multiple lung, bone,
      and lymph node metastases. Accordingly, we started docetaxel (75 mg/m) every 5
      weeks in consideration of myelosuppression for hormone-resistant multiple
      metastases. Although lung metastasis shrunk by one cycle docetaxel, radiotherapy
      for the thoracic and lumbar vertebrae was performed for back pain and lumbago. On
      day 21, at the end of radiotherapy, the same dose of docetaxel was administrated
      for the third time. On day 7, after third docetaxel administration, erythema
      appeared in a irradiated field of the thoracic and lumbar vertebra. Erythema
      primarily appeared on the anterior side of the body, and no skin reaction was
      noted on the posterior part of the thoracic irradiated area. Notably, no skin
      reaction was observed in the previously irradiated field for prostate cancer.
      CONCLUSIONS: This case report draws attention to the development of atypical RRD
      after administration of docetaxel and advises careful follow-up even if RRD does
      not appear after the first docetaxel administration.

PMID- 30200133
TI  - Endovascular management in immature arteriovenous fistula for hemodialysis.
AB  - To evaluate the outcomes and prognostic factors of endovascular management in
      immature arteriovenous fistula (AVF) for hemodialysis.From April 2007 to
      September 2017, 54 patients (male:female = 31:23, mean age 65.63 years, range 33
      90 years) who underwent endovascular management for the salvage of immature AVF
      were retrospectively reviewed. Clinical data, procedural details, and results
      were evaluated. Primary and secondary patency rates and factors influencing the
      patency were also analyzed.Technical and clinical success rates were 88.9%
      (48/54) and 85.2% (46/54), respectively. Mean primary and secondary patency was
      42.10 (+/-8.85) and 91.5 (+/-14.77) months, respectively. Primary and secondary
      patency rates were 66% and 89% in 1 year, 66% and 78% in 2 years, and 51% and 78%
      in 3 years. In multivariate analysis, only brachiocephalic AVF and antegrade
      access procedures showed significantly shorter primary patency (HR 5.196; 95% CI
      (1.04-25.77); P = .044, HR 8.096; 95% CI (1.36-48.00); P = .021). There was no
      statistically significant factor associated with secondary patency in the
      multivariate study.Endovascular management in immature AVF is safe and effective
      to make the AVF available. Brachiocephalic AVF and antegrade access procedures
      are the factors influencing the patency in multivariate analysis.

PMID- 30200134
TI  - Hospital readmission with Clostridium difficile infection as a secondary
      diagnosis is associated with worsened outcomes and greater revenue loss relative
      to principal diagnosis: A retrospective cohort study.
AB  - Recurrent Clostridium difficile infection (rCDI) requiring rehospitalization
      contributes to poor outcomes, which may differ between patients hospitalized with
      versus for it.We performed a multicenter retrospective cohort study of
      rehospitalized adults surviving initial CDI hospitalization. Hospital mortality,
      length of stay (LOS), 30-day readmission, and mean gap between hospital costs and
      Diagnosis Related Group (DRG) reimbursement served as outcomes.Among the 25.7% (n
      = 99,175) survivors requiring rehospitalization, 36,504 (36.8%) had rCDI (14,005
      [38.4%] principal diagnosis rCDI [PrCDI]). Compared with non-CDI, PrCDI, and
      secondary diagnosis rCDI [SrCDI] carried lower risk of death (PrCDI odds ratio
      [OR] 0.52; 95% confidence interval [CI] 0.46, 0.58; SrCDI OR 0.80; 95% CI 0.75,
      0.85) and 30-day readmission (PrCDI OR 0.84; 95% CI 0.80, 0.88; SrCDI OR 0.97;
      95% CI 0.94, 1.01), and excess LOS (PrCDI 1.8 days; 95% CI 1.7, 2.0; SrCDI 1.4
      days; 95% CI 1.3, 1.5), and costs (PrCDI $1399; 95% CI $858, $1939; SrCDI $2809;
      95% CI $2307, $3311). Mean gap between hospital costs and DRG reimbursements was
      highest in SrCDI ($13,803).A rehospitalization within 60-days of an initial CDI
      hospitalization occurs in approximately 25% of all survivors, 1/3 with rCDI.
      SrCDI carries worse outcomes than PrCDI. The potential loss of revenue incurred
      by the hospital is nearly 3-fold higher for SrCDI than PrCDI.

PMID- 30200135
TI  - Early precut sphincterotomy does not increase the risk of adverse events for
      patients with difficult biliary access: A systematic review of randomized
      clinical trials with meta-analysis and trial sequential analysis.
AB  - OBJECTIVE: The present study was conducted to investigate whether early precut
      sphincterotomy (EPS) itself increases the incidence of post-endoscopic retrograde
      cholangiopancreatography pancreatitis (PEP), bleeding, and perforation, or
      improves the overall success rates of biliary cannulation. METHODS: Four
      electronical databases were searched systematically for randomized controlled
      trials (RCTs) reporting the incidence of adverse events for difficult biliary
      access (DBA) between EPS groups and persistent cannulation attempts (PCA). The
      primary endpoint was the incidence of PEP. Secondary outcomes were the incidence
      of bleeding and perforation, and the overall success rates of biliary
      cannulation. The Mantel-Haenszel method was used to pool data on the outcomes
      into random-effect models. Heterogeneity, sensitivity, and stratified analyses
      were performed with Review Manager 5.3. Furthermore, we performed trial
      sequential analysis (TSA) to evaluate the reliability of the primary endpoint and
      secondary outcomes. RESULTS: Seven RCTs (999 patients with DBA of 10450, 9.5%)
      were included. The incidence of PEP was significantly lower in EPS groups than
      PCA (risk ratio [RR] = 0.57, 95% confidence interval [CI] 0.36, 0.92, P = .02).
      Furthermore, TSA (TSA-adjusted 95% CI 0.30-0.82, P = .0061) and subgroup analysis
      stratified by the fellow involvement in initial cannulation before randomization,
      technique of precut, and the definition of DBA confirmed this finding. Success
      rates of overall cannulation (RR = 1.00, P = .94), bleeding (RR = 1.22, P = .58),
      and perforation (RR = 1.59, P = .32) were similar in both groups; however, the
      results of TSA could not confirm these findings. CONCLUSION: Both the quality and
      the quantity of evidence supporting, compared with PCA, EPS itself do not
      increase the risk of PEP for DBA patients. Moreover, subgroup analysis
      demonstrated that EPS can significantly decrease the risk of PEP when it is
      performed by qualified staff endoscopists with using needle-knife fistulutomy
      earlier for patients with DBA.

PMID- 30200136
TI  - Whole exome sequencing detects CHST3 mutation in patient with acute promyelocytic
      leukemia: A case report.
AB  - RATIONALE: Acute promyelocytic leukemia (APL) is a kind of acute myeloid
      leukemia, which was characterized by the presence of PML/RARalpha fusion gene.
      Mutations in CHST3 have been previously reported to be associated with a rare
      phenotype of skeleton dysplasia, known as Spondyloepiphyseal dysplasia. Here we
      reported 1 patient with APL with CHST3 mutations. PATIENT CONCERNS: An 18-year
      old girl was referred to the Hematology Department because of a lasting history
      (10 days) of repeated fever and bleeding on skin. The girl was of short stature
      for age and with short fingers. Double nail beds were short with anti-nail
      deformity. DIAGNOSES: She was diagnosed with APL according to the 2016 WHO
      classification after a MICM analysis (bone marrow morphology [M], immunophenotype
      [I], cytogenetics [C], and molecular biology [M]). Whole exome sequencing
      revealed complex heterozygous mutations on CHST3. Further confirmation showed
      that 1 mutation (c.155T>G; p.Leu52Arg) was from her father and the other mutation
      (c.1414G>A; p.Glu472Lys) was from her mother. INTERVENTIONS: The patient received
      Idarubicin (8 mg/m) injection intravenous drip for 3 days based on all-trans
      retinoic acid and arsenic trioxide induction therapy. OUTCOMES: The patient died
      from disseminated intravascular coagulation and multiple organ hemorrhage at 9
      days after diagnosis. LESSONS: This case describes a patient with APL with
      complex heterozygous mutations on CHST3. Carbohydrate sulfotransferases were
      found to play an important role in metastatic spread of tumor cells. Whether the
      mutation status of CHST3 gene has relationship with APL pathogenesis and
      prognosis is unknown.

PMID- 30200137
TI  - False localizing sign caused by schwannoma in cervical spinal canal at C1-2
      level: A case report.
AB  - RATIONALE: False localizing sign means that the lesion, which is the cause of the
      symptom, is remote or distant from the anatomical site predicted by neurological
      examination. This concept contradicts the classical clinicoanatomical correlation
      paradigm underlying neurological examinations. PATIENT CONCERNS: A 54-year-old
      man consulted for the right sciatica-like leg pain that had aggravated 1 year
      ago. Radiological examinations revealed degenerative spondylolisthesis with
      instability and right-sided recess stenosis at the L4-5 level. After initial
      improvement following 3 transforaminal epidural steroid injections with
      gabapentin and antidepressant medication, there was a recurrence of the symptoms
      a year later, along with wasting of the right leg for several months. Physical
      examination revealed difficulty in heel-walking and a weakness of extension of
      the right big toe; tendon reflexes were normal. Lumbar spine radiographs revealed
      no new findings. The initial course of treatment was repeated, but was
      ineffective. DIAGNOSES: Further cervicothoracic spine evaluations revealed a
      right-sided intradural-extramedullary mass and myelopathy at the C1-2 level.
      INTERVENTIONS: The cervical mass was surgically resected and identified
      histopathologically as a schwannoma. OUTCOMES: Immediately after surgery,
      sciatica-like pain and weakness of right leg were completely resolved. LESSONS:
      It is difficult to make an accurate diagnosis if there are symptoms caused by
      false localizing sign. Additionally, it is even more difficult to diagnose false
      localizing sign accurately when there is a co-existing lumbar lesion that can
      cause the similar symptoms.

PMID- 30200138
TI  - Clinical and pathological study on mixed tumors of the skin.
AB  - Mixed tumor of the skin (MTS) is a rare benign tumor of the sweat glands with a
      reported frequency of 0.01% to 0.098%. The objective of the study is to
      investigate clinicopathological and immunohistochemical features of mixed tumor
      of the skin.This was a retrospective study of 21 patients diagnosed with MTS at
      the Institute of Dermatology and Venereology of Sichuan Provincial People's
      Hospital from 1980 to 2016. Pathological sections of all cases were reread and
      the diagnosis was verified.There were 14 males (67%) and 7 females (33%). MTS
      affected the face. The lesions were skin-colored or lightly red, with no
      subjective symptoms in most cases. Histopathologically, the tumors consisted of
      epithelial and interstitial components. The epithelium was mainly composed of
      cubic or polygonal cells, which can be seen within the tubule-like structures
      with bilayer epithelium. The inner cells mainly expressed cytokeratin and other
      epithelial markers. The outer cells expressed epithelial and mesenchymal markers.
      The outer cells expressed S-100, P63, and glial fibrillary acidic protein. The
      tumors showed interstitial mucus-like and fibrosis changes, and some parts had
      cartilage-like changes.Pathological diagnosis is particularly important because
      the clinical symptoms of MTS lack specificity.

PMID- 30200139
TI  - Analysis of seasonal tendencies in pediatric Henoch-Schonlein purpura and
      comparison with outbreak of infectious diseases.
AB  - Henoch-Schonlein purpura (HSP) is one of the most common vasculitis in children.
      This study was aimed at identifying seasonal trends and epidemiologic features of
      pediatric HSP patients through public data to analyze the correlation of HSP and
      prevalence of a specific respiratory or enteric virus.We extracted information on
      pediatric HSP patients categorized into 4 age groups and data on 8 respiratory
      and 4 enteric viruses were extracted from national data. We used the
      decomposition of time series analysis and correlation analysis to identify the
      incidence of HSP and the prevalence of each virus.From 2013 to 2016, 16,940
      patients under the age of 18 were diagnosed with HSP in Korea, 6203 (36.6%) were
      diagnosed with HSP in middle childhood. Spring had the largest number of patients
      (5252, 31.0%), and summer had the smallest number of patients (3224, 19.0%). The
      largest and smallest number of cases occurred in March (1949, 11.5%) and August
      (959, 5.7%), respectively. However, among the adolescents, more patients were
      diagnosed in the summer (985, 24.8%) than in the fall (760, 19.1%). The positive
      detection counts of most viruses showed apparent seasonal variations. Depending
      on the age group, the epidemic patterns of influenza and rotaviruses were
      temporally and statistically similar to that of HSP.We have confirmed that the
      occurrence of pediatric HSP in Korea shows a seasonal tendency, which is age
      dependent and related to exposure to infectious agents and suggest some
      respiratory or enteric viruses may play an important role in pathophysiology.

PMID- 30200140
TI  - Establishment of normal reference values of NT-proBNP and its application in
      diagnosing acute heart failure in children with severe hand food and mouth
      disease.
AB  - Hand, foot, and mouth disease (HFMD), caused by enteroviruses, is an acute
      contagious disease in children. Some severe infections caused by human
      enterovirus 71 (HEV71) lead to rapid death in children with acute heart failure
      (HF). N-terminal probrain natriuretic peptide (NT-proBNP) is an important
      indicator of HF; however, its normal reference values in children and role in
      HFMD remain unclear.This study aimed to investigate the correlation between NT
      proBNP and heart function and establish normal reference values of NT-proBNP in
      children with HFMD aged 0 to 18 years.In this study, 95% normal reference values
      were established in 1031 healthy children aged 0 to 18 years. The correlation
      between NT-proBNP and left ventricular ejection (LVEF) was analyzed in 392
      children with HFMD using Spearman correlation and receiver operating
      characteristic analysis.NT-proBNP levels were negatively correlated with LVEF in
      392 children with HFMD. The median NT-proBNP level was 921 pg/mL in the early
      cardiorespiratory failure group, but only 55 pg/mL in the nervous system
      involvement group. Serum NT-proBNP levels were negatively correlated with age.
      The normal reference value in the neonatal period (0 to <1 month) and adolescence
      (13-18 years) was 250.0 to 3987.0 pg/mL and 20.0 to 145.0 pg/mL, respectively.NT
      proBNP levels can reflect the severity of HFMD and discriminate the second stage
      from the third stage of HFMD effectively. NT-proBNP is a useful biomarker to
      predict the early stage of severe HFMD in children with HF. Different ages fit
      with different normal reference values of NT-proBNP in children.

PMID- 30200141
TI  - Acid base variables predict survival early in the course of treatment with
      continuous venovenous hemodiafiltration.
AB  - Metabolic acid-base disorders, especially metabolic acidosis, are common in
      critically ill patients who require renal replacement therapy. Continuous veno
      venous hemodiafiltration (CVVHDF) achieves profound changes in acid-base status,
      but metabolic acidosis can remain unchanged or even deteriorate in some patients.
      The objective of this study is to understand the changes of acid-base variables
      in critically ill patients with septic associated acute kidney injury (SA-AKI)
      during CVVHDF and to determine how they relate to clinical outcome.Observational
      study of 200 subjects with SA-AKI treated with CVVHDF for at least 72 hours.
      Arterial blood gases and electrolytes and other relevant acid-base variables were
      analyzed using quantitative acid-base chemistry.Survivors and nonsurvivors had
      similar demographic characteristics and acid-base variables on day one of CVVHDF.
      However, during the next 48 hours, the resolution of acidosis was significantly
      different between the 2 groups, with an area under the ROC curve for standard
      base excess (SBE) and mortality of 0.62 (0.54-0.70), this was better than APACHE
      II score prediction power. Quantitative physicochemical analysis revealed that
      the majority of the change in SBE was due to changes in Cl and Na
      concentrations.Survivors of SA-AKI treated with CVVHDF recover hyperchloremic
      metabolic acidosis more rapidly than nonsurvivors. Further study is needed to
      determine if survival can be improved by measures to correct acidosis more
      rapidly.

PMID- 30200143
TI  - The use of extracorporeal membrane oxygenation in trauma patients: A national
      case-control study.
AB  - Extracorporeal membrane oxygenation (ECMO) has been increasingly applied for the
      treatment of patients with trauma. Because a common complication of ECMO is
      bleeding, the use of ECMO support for patients with trauma was limited in the
      past. Studies have demonstrated a survival benefit from ECMO support in cases of
      traumatic lung injury, and it is likely that patients with other types of trauma
      would also benefit from ECMO support. However, the effect of ECMO in patients
      with other types of trauma is unknown.Using the national insurance data of
      Taiwan, we identified 810 patients with trauma who received ECMO support from
      2000 to 2010. Patients who died or who withdrew from the program within 7 days
      after discharge were defined as deceased. Logistic regression was used to
      estimate the odds ratio (OR) of death and 95% confidence intervals (CIs).The
      overall mortality was 32.8% (266/810). A total of 417 patients received surgery
      during hospitalization, with an overall mortality of 39.0% (163/417). Patients
      who underwent thoracic surgery had an OR of 2.23 (95% CI: 1.49-3.34) compared
      with those who did not. Patients who underwent brain surgery had an OR of 2.86
      (95% CI: 1.37-5.98) compared with patients who did not. Patients who received
      abdominal surgery had an OR of 4.47 (95% CI: 2.63-7.61) compared with patients
      who did not. All types of surgery had odds of mortality except orthopedic
      surgery; the use of ECMO with orthopedic surgery had an OR of 1.06 (95% CI: 0.69
      1.62) compared with patients who did not receive orthopedic surgery.Except for
      orthopedic surgery, patients with trauma who received ECMO support and required
      further surgery during hospitalization exhibited a relatively high mortality
      rate.

PMID- 30200142
TI  - Comparison of apatinib and capecitabine (Xeloda) with capecitabine (Xeloda) in
      advanced triple-negative breast cancer as third-line therapy: A retrospective
      study.
AB  - The treatment of advanced triple-negative breast cancer, which failed in first
      line or second-line therapy, is a significant challenge. We conducted this
      retrospective study to explore the efficacy and safety of apatinib and
      capecitabine as the third-line treatment for advanced triple-negative breast
      cancer.This retrospective study involved 44 advanced triple-negative breast
      cancer patients who failed in first-line or second-line therapy in Tangshan
      People's Hospital from January 2016 to February 2017. Twenty-two patients
      received apatinib and capecitabine, while 22 patients were treated with
      capecitabine monotherapy as third-line therapy. The progression-free survival
      (PFS), objective response rate (ORR), disease control rate (DCR), and adverse
      events were compared between 2 groups.The apatinib and capecitabine group
      exhibited a higher PFS than capecitabine group (P = .001). Meanwhile, ORR and DCR
      in apatinib and capecitabine group were better than in capecitabine group (P =
      .042; .016). The 2 groups showed no significant difference in adverse events
      except degree I-II bleeding (P = .021). Both the apatinib and capecitabine and
      the capecitabine regimens revealed good tolerability.The apatinib and
      capecitabine regimen can achieve a better efficacy and similar serious adverse
      events compared with capecitabine regimen as the third-line treatment for
      advanced triple-negative breast cancer.

PMID- 30200144
TI  - Application of multidimensional interpolation on nonhomogeneous cancellous bone.
AB  - Bone, especially cancellous bone, has been demonstrated to be nonhomogeneous.
      When applied to bone study, it raises the following question: How should the
      material properties of the bone from the available experimental data be
      interpolated?In this study, the finite element model of the femur has been built
      and the nonhomogeneous material properties of the femur have been assigned from
      the computed tomography (CT) data. These results have been applied to assess some
      common interpolation algorithms on the bone study, such as Linear Multivariate,
      Radial Basis, and Nearest Neighbor. It was found that among 3 tested algorithms,
      the RBAS algorithm has more points with errors from 0% to 15% than in the other 2
      algorithms. When the supporting points jump from 160 to 288, the interpolation
      results significantly improve. When the finite element model reduces the element
      number from 38,230 to 13,424, all 3 algorithms have slightly better results.The
      interpolation of bone material properties should use 2 different approaches. The
      bone interpolation should be applied only to the bone with uniform structure. For
      the area with dramatic change of structure, the material properties can be
      defined directly. Among 3 tested algorithms, the Radial Basis algorithm performs
      best in the statistic study and should be the first choice in the bone study. In
      addition, the Radial Basis algorithm can be introduced into other methods to
      smooth the distribution of material properties. Also, with more supporting points
      (experimental data), the interpolation error becomes less. The interpolation
      approach offers a significant advantage in the finite element analysis: only 1
      material ID needs to define the material interpolated from experimental data,
      unlike the several hundred material IDs defined for the elements derived from CT
      data that take material inhomogeneity into account.

PMID- 30200145
TI  - Awareness and use of pre-exposure and postexposure prophylaxes among Nigerian
      university students: Findings from a cross-sectional survey.
AB  - Despite the recent advances in biomedical preventive strategies, young adults
      especially adolescent girls- continue to be disproportionately at risk of
      acquiring HIV. To avert this trend, it is critical that access to HIV preventive
      strategies, such as pre-exposure prophylaxis (PrEP) and postexposure prophylaxis
      be expanded, especially in sub-Saharan Africa, where young adults are known to
      engage in risky sexual practices. This study examined awareness levels and use of
      pre-exposure prophylaxis (PrEP) and postexposure prophylaxis (PEP) among Nigerian
      university students.A cross-sectional survey was conducted among 800 students
      selected using stratified random sampling at 2 Nigerian universities. Descriptive
      and inferential statistics were used for data analysis on 784 complete
      responses.The levels of awareness of PrEP and PEP were 18.9% and 25.4%,
      respectively. Ever tested for human immunodeficiency virus [HIV] (AOR: 1.58; 95%
      CI: 1.04-2.42) and knowledge of partner's HIV status (AOR: 1.87; 95% CI: 1.25
      2.79) were the significant determinants of awareness to PrEP. In contrast, only
      ever tested for HIV (AOR: 1.50; 95% CI: 1.02-2.19), knowledge of partner's HIV
      status (AOR: 1.55; 95% CI: 1.07-2.24), ever used condoms (AOR: 1.65; 95% CI: 1.04
      2.62), and nude exchanges (AOR: 1.62; 95% CI: 1.13-2.31) were independent
      determinants of awareness of PEP. Only a few students had seen (5.6%) or used
      (1.5%) any prophylaxes.The study findings indicate a low level of awareness and
      use of PrEP and PEP. To ensure no one is left behind in the goal of elimination
      of new HIV infections, intervention to expand access to these preventive
      strategies is needed in the study settings.

PMID- 30200146
TI  - The role of fluorescence in situ hybridization to predict patient response to
      intravesical Bacillus Calmette-Guerin therapy for bladder cancer: A diagnostic
      meta-analysis and systematic review.
AB  - BACKGROUND: The aim of the study was to systematically review the relevant
      studies to assess the role of fluorescence in situ hybridization (FISH) test for
      predicting patient response to Bacillus Calmette-Guerin (BCG) therapy after
      transurethral resection of bladder tumor (TURBT). METHODS: We searched PubMed,
      Embase, and the Cochrane Library from inception to July 5, 2018, and used Quality
      Assessment Tool for Diagnosis Accuracy Studies (QUADAS-2) to assess the quality.
      We pooled sensitivity, specificity, and area under curve (AUC) of baseline and
      post-BCG FISH test for predicting tumor recurrence. Hazard ratio (HR) with 95%
      confidence intervals (95% CIs) and a Fagan nomogram were applied to assess
      predictive accuracy of post-BCG FISH test. RESULTS: A total of 6 studies with 442
      participants for post-BCG test and 404 participants for baseline BCG test were
      included. The pooled analysis for post-BCG FISH test revealed the sensitivity of
      0.54 (95% CI 0.38-0.69), specificity of 0.84 (95% CI: 0.72-0.91), and area under
      the curve (AUC) of 0.78 (95% CI: 0.74-0.81) for predicting tumor recurrence.
      Patients with positive post-BCG FISH test were more likely to recur during follow
      up (HR 3.95, 95% CI 2.72-5.72). The Fagan nomogram revealed the "post-test"
      probability of tumor recurrence increased by 29% for patients with positive post
      BCG FISH test. The baseline FISH test had a pooled sensitivity of 0.70 (95% CI
      0.55-0.81), specificity of 0.41 (95% CI: 0.26-0.58), and AUC of 0.60 (95% CI:
      0.56-0.64) for predicting recurrence. CONCLUSION: The post-BCG FISH test can
      predict BCG failure with high specificity and patients with positive post-BCG
      FISH test were more likely to recur. However, the relatively low sensitivity of
      post-BCG FISH test and unsatisfactory performance of baseline FISH test may limit
      their mono-use.

PMID- 30200147
TI  - The comparison of propofol and midazolam for bronchoscopy: A meta-analysis of
      randomized controlled studies.
AB  - BACKGROUND: Propofol and midazolam are widely used for the sedation of
      bronchoscopy. This systematic review and meta-analysis is conducted to compare
      the efficacy of propofol and midazolam for bronchoscopy. METHODS: The databases
      including PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases
      are systematically searched for collecting the randomized controlled trials
      (RCTs) regarding the efficacy of propofol and midazolam for bronchoscopy.
      RESULTS: This meta-analysis has included 4 RCTs. Compared with midazolam
      intervention in patients undergoing bronchoscopy, propofol intervention is
      associated with remarkably reduced recovery time [standard mean difference (SMD)
      = -0.74; 95% confidence interval (95% CI) = -1.04 to -0.45; P < .00001], but
      demonstrates no significant impact on operation time (SMD = -0.01; 95% CI = -0.16
      to 0.13; P = .87), induction time (SMD = -0.58; 95% CI = -1.19 to 0.03; P = .06),
      lowest oxyhemoglobin saturation (SpO2, SMD = 0.24; 95% CI = -0.09 to 0.58; P =
      .15), SpO2 <90% [risk ratio (RR) = 1.02; 95% CI = 0.82-1.25; P = .88), and major
      arrhythmias (RR = 0.56; 95% CI = 0.26-1.19; P = .13). CONCLUSION: Propofol
      sedation is able to reduce recovery time and shows similar safety compared with
      midazolam sedation during bronchoscopy.

PMID- 30200148
TI  - Cytokine-induced killer cell/dendritic cell-cytokine-induced killer cell
      immunotherapy for the postoperative treatment of gastric cancer: A systematic
      review and meta-analysis.
AB  - BACKGROUND: Immunotherapy is emerging as a new treatment strategy for gastric
      cancer(GC). However, the efficacy and safety of this technique remain unclear.
      This meta-analysis aimed to assess the effect of cytokine-induced killer cell
      (CIK)/dendritic cell-cytokine-induced killer cell (DC-CIK) treatment for GC after
      surgery. METHODS: Hazard ratio (HR), overall survival (OS) rates, and disease
      free survival (DFS) rates were calculated using a Mantel-Haenszel (M-H) fixed
      effects model (FEM), and results were displayed using forest plots. Publication
      bias was assessed by Begg test, and data were presented using funnel plots. Date
      robustness was assessed by the trim and fill method. Descriptive analysis was
      performed on T lymphocytes and adverse effects. RESULTS: In total, 9 trials,
      including 1216 patients, were eligible for inclusion in this meta-analysis.
      Compared with the control group, the HR for OS was 0.712 (95% confidence interval
      [CI] 0.594-0.854) and 0.66 (95% CI 0.546-0.797) for overall (DFS). The risk ratio
      (RR) of the 3 and 5-year OS rate was 1.29 (95% CI 1.15-1.46) and 1.73 (95% CI
      1.36-2.19), respectively. The RR for the 3 and 5-year DFS rate 1.40 (95% CI 1.19
      1.65) and 2.10 (95% CI1.53-2.87), respectively. The proportion of patients who
      were CD3+, CD4+, and CD4+/CD8+ increased in the cellular therapy groups. No fatal
      adverse reactions were noted. CONCLUSION: Chemotherapy combined with CIK/DC-CIK
      therapy after surgery resulted in low HR, and significantly increasing OS rates,
      DFS rates, and T-lymphocyte responses in patients with GC.

PMID- 30200149
TI  - Comparative proteomic analysis of maternal peripheral plasma and umbilical venous
      plasma from normal and gestational diabetes mellitus pregnancies.
AB  - Gestational diabetes mellitus (GDM) increases many health risks in offspring. The
      study aims to investigate the underlying mechanism in fetal risk of GDM.We
      collected maternal peripheral plasma and umbilical venous plasma samples from 4
      GDM and 4 control patients during their delivery at a university-based women's
      hospital. An isobaric tag for relative and absolute quantitation-labeled
      proteomics analysis was performed. The enzyme-linked immunosorbent assay was used
      to confirm the change of cholesteryl ester transfer protein (CETP). Bioinformatic
      analysis was performed with Ingenuity Pathway Analysis (IPA) software package.We
      identified 19 up-regulated proteins and 15 down-regulated proteins in GDM
      peripheral plasma, 29 up-regulated proteins and 69 down-regulated proteins in GDM
      umbilical venous plasma. CETP concentration was significantly lower in both GDM
      peripheral plasma and umbilical venous plasma. Upstream regulator analysis
      predicted follicle-stimulating hormone (FSH) as the activated regulator of
      differentially expressed proteins.The protein profiles in both GDM peripheral
      plasma and umbilical venous plasma between normal and GDM patients were
      significantly different. The results indicated that CETP and FSH might associates
      with health problem of GDM offspring.

PMID- 30200150
TI  - The association between rs12885713 polymorphism in CALM1 and risk of
      osteoarthritis: A meta-analysis of case-control studies.
AB  - OBJECTIVE: The single nucleotide polymorphism (SNP) rs12885713 of calmodulin 1
      gene (CALM1) has been reported to involve in the etiology of osteoarthritis (OA)
      in several association studies with limited sample size and conflicting results.
      The purpose of the present systematic review and meta-analysis was to evaluate
      and synthesize the currently available data on the correlation between rs12885713
      and OA susceptibility. METHODS: Six electronic databases including PubMed,
      EMBASE, ISI Web of Science, CNETRAL, CNKI, and Wanfang were systematically
      retrieved to identify relevant observational articles published before October
      2017. Summary odds ratios (ORs) and corresponding 95% confidence intervals (95%
      CIs) were calculated to indicate the association between CALM1 polymorphism and
      OA. Risk of bias was assessed through the Newcastle-Ottawa Scale. Predetermined
      subgroups and sensitivity analyses were performed using the RevMan 5.3 software.
      Publication bias was evaluated by Egger and Begg tests. RESULTS: Overall, 5 case
      control studies involving 2183 OA patients 2654 healthy control subjects
      satisfied the meta-analysis. Recessive model was confirmed to be the best
      matching genetic model (TT + TC versus CC). The pooled outcomes indicated that
      rs12885713 SNP was not significantly associated with OA vulnerability (OR 1.11,
      95% CI 0.97, 1.27; P = .12). When stratified by different genders, OA sites, and
      population descents respectively, still non-significant associations were found.
      CONCLUSION: Based on the findings of our present study, the rs12885713
      polymorphism of CALM1 did not appear to be associated with OA predisposition.

PMID- 30200151
TI  - One-lung ventilation in a patient with a large mass on the glottis: A case
      report.
AB  - RATIONALE: One-lung ventilation (OLV) is required during most thoracic surgeries
      to facilitate surgical visualization by collapsing the lung. Double-lumen tubes
      and bronchial blockers are two commonly used devices for OLV; however, it may be
      difficult to place two devices in patients with narrow inlets, such as those that
      have tumor-induced airway stenosis. PATIENT CONCERNS: We report the case of an
      adult patient with a lung tumor that was growing rapidly and hemorrhaging; thus,
      a thoracotomy for lung resection should have been performed as early as possible.
      However, a large mass on the glottis obstructed the entry of the double-lumen
      tube or bronchial blocker. Therefore, the operation could not be performed
      because of the inability to provide one-lung ventilation via the conventional
      intubation method. DIAGNOSES: Computed tomography (CT) revealed a lung tumor that
      was growing rapidly and preoperative bronchoscopy showed a large mass on the
      vocal cords. INTERVENTIONS: After anesthesia induction, a Uniblocker and a small
      single lumen tube were intubated and the Uniblocker was inserted extraluminally
      of the single lumen tube. One-lung ventilation was achieved successfully in this
      patient. OUTCOMES: The surgery proceeded uneventfully for 4 hours without any
      complications. LESSONS: Extraluminal use of the Uniblocker and a small single
      lumen tube may be recommended for patients receiving OLV and who have narrow
      inlets, especially under emergency situations.

PMID- 30200152
TI  - Endothelial nitric oxide synthase (-786T>C) polymorphism and migraine
      susceptibility: A meta-analysis.
AB  - BACKGROUND: The aim of this study was to evaluate the correlation between
      endothelial nitric oxide synthase (eNOS) polymorphism (-786T>C) and migraine
      susceptibility in a meta-analysis. METHODS: A literature search was performed for
      case-control studies from inception to July 30, 2018 focusing on eNOS
      polymorphism (-786T>C) and risk of migraine. From 454 full-text articles, 6 were
      included in this study. Heterogeneity was assessed with the I index and quality
      assessment was performed using the Newcastle-Ottawa scale. RESULTS: CC genotype
      was not related to higher susceptibility of migraine compared with TT+ TC
      genotypes with significant difference (fixed effects model; OR = 1.27; 95% CI =
      0.90-1.80; P = .17; I = 18%). However, subgroup analysis showed CC variant
      increase the risk for migraine compared with TT+ TC genotypes in Caucasian
      populations (fixed effects model; OR = 1.62; 95% CI = 1.03-2.56; P = .04; I =
      18%), which could not be observed in non-Caucasian populations (fixed effects
      model; OR = 0.88; 95% CI = 0.51-1.53; P = .66; I = 0%). There was no significant
      difference for other genotypes and alleles between patients with migraine and
      healthy controls (all P > .05). CONCLUSION: This meta-analysis indicated that CC
      variant increases the risk for migraine compared with TT + TC genotypes in
      Caucasian populations.

PMID- 30200153
TI  - Changes of serum midkine as a dynamic prognostic factor to monitor disease status
      in papillary thyroid cancer.
AB  - This study aimed to investigate the value of dynamic changes of midkine (MK) to
      monitor post-surgical patients with papillary thyroid cancer (PTC) who were
      managed with I therapies.MK concentration at initial I ablation therapy (MK1) as
      well as 10 to 12 months thereafter (MK2) was evaluated. And the dynamic changes
      of thyroglobulin (Tg) were compared (Tg1 and Tg2). Patients with MK influencing
      co-morbidities and with positive thyroglobulin antibodies were excluded.
      Concentrations of MK were measured by enzyme-linked immunosorbent assay.There
      were 241 PTC patients (36 males, 205 females) enrolled, 55 cases had metastases
      (8 males, 47 females) during their follow-up. Cox regression showed if Tg2
      decreased (compared with Tg1), but not to less than 1.0ng/mL under TSH
      stimulation, the risk of metastases was 12.554 times more than if it could
      decrease to the optimal level. If Tg2 increased, the risk is 19.461 times higher.
      As for MK, if MK2 level decreased (compared with MK1), but not to a normal level,
      the risk of metastases is 3.006. If MK2 level increased, it would be 5.030 likely
      to had metastases.Our results indicated that MK could potentially be used as a
      disease monitoring biomarker for PTC, although inferior to Tg.

PMID- 30200154
TI  - Retrospective analysis of smaller than 3-cm umbilical hernia repair with the
      lightweight macroporous mesh.
AB  - There is evidence that mesh repair for primary umbilical hernias results in fewer
      recurrences and similar wound complication rates compared to tissue repair.
      Various devices and surgical approaches are used in umbilical hernia repair. The
      ULTRAPRO PLUG (UPP) has been adopted for inguinal hernias and femoral hernias
      with excellent results. However, there are few reports on the use of UPP for
      umbilical hernia repair. Thus, the aim of this study was to evaluate efficacy and
      safety in the treatment of smaller than 3-cm umbilical hernias using the UPP.The
      medical records of 123 patients who underwent umbilical hernia repair using the
      UPP between October 2011 and September 2017 were reviewed. All patients were
      followed-up after 1 month and later in 2018. Demographics, surgical information,
      and immediate postoperative and long-term complications were assessed.Out of 123
      patients, there were 37 male and 86 female patients with a mean age of 50.6
      years. The median duration of hernia surgery was 20.5 min (range, 12-34), and 109
      (88.6%) patients underwent day surgery. The median defect diameter was 1.4 cm
      (range, 0.5-3). No mortality or major complications occurred during the
      perioperative period. Long-term follow-up data were available for 107 (87.0%)
      patients. The median follow-up duration was 33 months (range, 5-76 months). Early
      postoperative complications included 1 case of seroma, 2 cases of fat
      liquefaction, and 1 case of superficial surgical site infection. During follow
      up, there were 2 recurrences, 1 case of chronic mesh infection, and 2 patients
      with chronic postoperative pain.The ULTRAPRO PLUG offers a simple and quick means
      of repairing smaller than 3-cm umbilical hernias with lower recurrence rates and
      fewer postoperative complications.

PMID- 30200157
TI  - Pseudoaneurysm associated with arteriovenous fistula involving a superficial
      breast arteriole after vacuum-assisted removal of a benign mass: A case report.
AB  - RATIONALE: Pseudoaneurysm (PA) with associated arteriovenous fistula (AVF) is
      most often secondary to vascular catheterization, percutaneous biopsy, surgery,
      or trauma. PA-AVF occurs mainly in large or median arterial territories but
      rarely in the superficial arterioles of the breast. PATIENT CONCERNS: A 30-year
      old woman underwent vacuum-assisted removal of breast fibroadenomas under
      ultrasonic guidance. On the follow-up visit, the patient complained of a painful
      enlarging lump in her left breast. DIAGNOSES: An iatrogenic breast PA-AVF was
      diagnosed. INTERVENTIONS: The patient was treated with surgical excision and
      ligation under local anesthesia. OUTCOMES: At the 1-month follow-up, the wound
      was found to have healed well, and breast PA-AVF was eradicated. LESSONS: Vacuum
      assisted removal has been the first-line intervention for benign mass resection
      because of minimal invasion, but the risk of serious vascular complications
      remains. Careful duplex ultrasound examination prior to the procedure is highly
      recommended.

PMID- 30200155
TI  - Cross-talk between shoulder and neck pain: an imaging study of association
      between rotator cuff tendon tears and cervical foraminal stenosis.
AB  - Rotator cuff tendon tears are prevalent in patients with shoulder pain, the third
      most common musculoskeletal complaint. As shoulders are largely innervated by
      cervical nerves, it seems possible that rotator cuff pathology could have an
      association with cervical spine disorders, although few studies have investigated
      this possibility. This study aimed to explore the association between rotator
      cuff tendon tears and cervical radiculopathy (at C5 and C6 levels) in the
      shoulder pain population.We conducted a retrospective review of a clinical
      registry of shoulder ultrasound (US) examinations and cervical spine radiographs,
      recruiting a total of 126 patients with cervical spine radiographs taken within 1
      year of US examinations. Foraminal stenosis was grouped into 4 categories: C4/5
      intervertebral foramen only, C5/6 intervertebral foramen only, both C4/5 and C5/6
      intervertebral foramina, and neither C4/5 nor C5/6 intervertebral foramen. The
      groups with and without rotator cuff tendon tears were compared for various
      factors, using the Mann-Whitney U test for continuous variables and the chi test
      for categorical variables. A multivariate analysis was conducted using a logistic
      regression model to investigate the association between rotator cuff tendon tears
      and cervical foraminal stenosis.Patients with rotator cuff tendon tears tended to
      be older and had more night-time pain. No significant association was identified
      between rotator cuff tendon tears and cervical foraminal stenosis at C5 and C6
      levels. The only factor significantly predicting rotator cuff tendon tears was
      old age (odds ratio, 1.04; 95% confidence interval: 1.00-1.09).In patients with
      shoulder or neck pain, no significant association existed between rotator cuff
      tendon tears and cervical foraminal stenosis (at the C5 and C6 levels). When
      patients present with undifferentiated shoulder and neck pain, physicians should
      take a detailed history, perform physical examinations and imaging studies of
      both the neck and shoulder regions.

PMID- 30200156
TI  - Integrative Korean medicine as a possible conservative treatment for mild
      cervical spondylotic myelopathy: One-year follow-up case report (CARE-compliant).
AB  - RATIONALE: Cervical spondylotic myelopathy (CSM) is the most common spinal cord
      disorder in older patients. The purpose of this case report is to introduce
      conservative treatment with integrative Korean medicine (KM) as a possible
      alternative to surgery in patients with mild CSM. PATIENT CONCERNS: An 81-year
      old male with both hand weakness and dysesthesia was diagnosed with CSM and was
      recommended laminectomy. However, considering the patient's age and the
      underlying disease, he refused immediate surgery and preferred KM treatment
      DIAGNOSES:: The diagnosis of mild CSM was based on a modified Japanese Orthopedic
      Association (mJOA) score as well as the presence of compression on the spinal
      cord in magnetic resonance imaging findings INTERVENTIONS:: Integrative KM
      treatment consisting of acupuncture, acupotomy, Bee venom herbal acupuncture,
      cupping therapy, moxibustion, and herbal medicine was provided during the 12-week
      admission. OUTCOMES: Clinical improvement was detected with a mJOA score (11 to
      17), a numerical rating scale for dysesthesia intensity (5 to 2), finger escape
      sign (+/+ to +/-), grip and release test (11/14 to 32/31) and grasp power
      measured by dynamometer (3.1/9.7 to 10.8/18.3 kg) at 12 weeks. This improvement
      was maintained without surgery until 1 year. LESSONS: This case suggests that
      integrative KM was a possible conservative management option for mild CSM.

PMID- 30200158
TI  - Management of traumatic hemipelvectomy through ERAS pathway: A case report.
AB  - RATIONALE: Traumatic hemipelvectomy is a rare but life-threatening injury that
      involves separation of the pelvic ring from pubic symphysis usually results from
      high energy trauma and associated with other injuries. PATIENT CONCERN: In this
      report, we describe a case of traumatic hemipelvectomy, who presented in
      hemorrhagic shock associated with other injuries such as: right groin injury with
      limitation of passive movement of right hip and knee joint, left pelvic visceral
      protruded out, and wrapped by peritoneum, all of the vulva and anal tear, lumbar
      vertebrae transverse process fracture. DIAGNOSES: Traumatic hemipelvectomy.
      INTERVENTIONS: The patient was managed through enhanced recovery after surgery
      (ERAS) pathway with multidisciplinary coordination. OUTCOMES: Patient was able to
      walk with prosthesis or crutch, with associated injuries managed appropriately.
      The course was complicated with hemorrhagic shock and infection which were dealt
      promptly, with good recovery. LESSONS: In our case, the multimodal management
      through ERAS path has helped decrease stress level, decrease complication,
      decrease morbidity, decrease the length of stay in the hospital, and aid in
      faster recovery.

PMID- 30200159
TI  - Sciatic neuropathy caused by a pressure ulcer: A case report.
AB  - RATIONALE: Sciatic neuropathy has various causes; however, cases in which a
      pressure ulcer led to sciatic neuropathy have not been reported to date. PATIENT
      CONCERNS: A 33-year-old woman with no pre-existing mobility problems visited our
      department with the chief complaint of an extensive pressure ulcer and necrosis
      in her right buttock. She had a medical history of being bedridden for 2 days
      while in a coma due to a drug overdose 2 months previously. Physical examination
      revealed loss of sensation and foot drop in the right foot. DIAGNOSIS: Physical
      examination, magnetic resonance imaging, and nerve conduction studies were
      conducted; the patient was diagnosed with a common peroneal branch injury of the
      right sciatic nerve. INTERVENTIONS: The necrotic tissue was debrided and sciatic
      nerve decompression was performed, followed by frequent dressing changes. In
      addition, psychiatric treatment and physical therapy were performed
      simultaneously. OUTCOMES: The pressure ulcer decreased in size and healed to some
      extent with granulation tissue. However, gait disorders, accompanied by symptoms
      of sciatic neuropathy, continued. The patient was transferred to the department
      of gastroenterology for the treatment of toxic hepatitis, which occurred during
      her inpatient treatment. LESSONS: Physicians should be aware that sciatic
      neuropathy may occur during the treatment of patients with a pressure ulcer who
      exhibit no symptoms of paraplegia or quadriplegia. To prevent neuropathy,
      aggressive treatment of the pressure ulcer is necessary.

PMID- 30200161
TI  - The beneficial effect of air cleanliness with ISO 14644-1 class 7 for surgical
      intervention in a neonatal intensive care unit: A 10-year experience.
AB  - Whether critically ill neonates needing a surgical intervention should be
      transferred to an operating room (OR) or receive the intervention in a neonatal
      intensive care unit (NICU) is controversial. In this study, we report our
      experience in performing surgical procedures in a NICU including air
      cleanliness.This was a retrospective study performed at a metropolitan hospital.
      The charts of all neonates undergoing surgical procedures in the NICU and OR were
      retrospectively reviewed from January 2007 to June 2017. Data on baseline
      characteristics, procedure and duration of surgery, ventilator use, hypothermia,
      instrument dislocations, surgery-related infections and complications, and
      outcomes were analyzed.Ninety-two neonates were enrolled in this study, including
      44 in the NICU group and 48 in the OR group. The air cleanliness was
      International Organization for Standardization (ISO) 14644-1 class 7 in the NICU
      and class 5-6 in the OR. The NICU group had a younger gestational age and lower
      birth body weight than the OR group. The OR group had a higher incidence of
      hypothermia than in the NICU group (56.3% vs 9.1%, P < .001). However, there were
      no significant differences in surgical site related infections or mortality
      between the 2 groups.This study suggests that performing surgical procedures in a
      NICU with air cleanliness class 7 is as safe as in an OR, as least in part, when
      performing patent ductus arteriosus ligation and exploratory laparotomy.

PMID- 30200160
TI  - Calcified peripancreatic lymph nodes in pancreatic and hepatic tuberculosis
      mimicking pancreatic malignancy: A case report and review of literature.
AB  - RATIONALE: Tuberculosis remains a serious menace to the health of people.
      Isolated hepatic tuberculosis is rare and pancreatic tuberculosis is extremely
      rare. The preoperative diagnosis of pancreatic tuberculosis remains a great
      challenge. PATIENT CONCERNS: A 58-year-old Asian woman was referred to our
      hospital for evaluation of low back pain for 4 years and abdominal pain for 1
      month. DIAGNOSES: Computed tomography (CT) of the abdomen showed a hypodense mass
      in the pancreatic head and neck with abundant calcifications, a hypodense lesion
      in the liver without calcification, peripancreatic lymphadenopathy,
      calcifications in some lymph nodes. CT-guided fine needle aspiration biopsy of
      the hepatic lesion was carried out and the cytological examination revealed
      hepatic tuberculosis. INTERVENTIONS: The patient was treated with antituberculous
      therapy for 1 year. OUTCOMES: Low back pain and abdominal pain disappeared 3
      months after initial treatment and after 2 year of follow-up, the patient was
      asymptomatic. LESSONS: Our data hint that calcifications in both pancreatic
      lesions and peripancreatic lymph nodes may suggest pancreatic tuberculosis rather
      than pancreatic malignancy.

PMID- 30200162
TI  - Surveillance or no surveillance for deep venous thrombosis and outcomes of
      critically ill patients: A study protocol and statistical analysis plan.
AB  - OBJECTIVE: Surveillance ultrasounds in critically ill patients detect many deep
      venous thrombi (DVTs) that would otherwise go unnoticed. However, the impact of
      surveillance for DVT on mortality among critically ill patients remains unclear.
      DESIGN: We are conducting a multicenter, multinational randomized controlled
      trial that examines the effectiveness of adjunct intermittent pneumatic
      compression use with pharmacologic thromboprophylaxis compared to pharmacologic
      thromboprophylaxis alone on the incidence of proximal lower extremity DVT in
      critically ill patients (the PREVENT trial). Enrolled patients undergo twice
      weekly surveillance ultrasounds of the lower extremities as part of the study
      procedures. We plan to compare enrolled patients who have surveillance
      ultrasounds to patients who meet the eligibility criteria but are not enrolled
      (eligible non-enrolled patients) and only who will have ultrasounds performed at
      the clinical team's discretion. We hypothesize that twice-weekly ultrasound
      surveillance for DVT in critically ill patients who are receiving
      thromboprophylaxis will have more DVTs detected, and consequently, fewer
      pulmonary emboli and lower all-cause 90-day mortality. DISCUSSION: We developed a
      detailed a priori plan to guide the analysis of the proposed study and enhance
      the validity of its results.

PMID- 30200163
TI  - Effects of chemoradiotherapy and chemotherapy on survival of patients with
      locally advanced pancreatic cancer: A meta-analysis of randomized controlled
      trials.
AB  - To comparatively evaluate chemoradiotherapy (CRT) and chemotherapy (CT) for the
      treatment of locally advanced pancreatic cancer (LAPC) by meta-analysis.A
      literature search was performed until August 2016 to identify comparative studies
      assessing survival rates and complications. Pooled odds ratios (ORs) and 95%
      confidence intervals (95% CIs) were determined with the fixed or random effects
      model.Five randomized controlled trials (RCTs) met the defined inclusion
      criteria. A total of 593 patients were included, with 295 and 298 treated with
      CRT and CT, respectively. Overall survival showed no statistically significant
      difference in patients treated with CRT and CT at 6, 12, 18, and 24 months
      (respectively: OR = 1.13, 95% CI: 0.60-2.17; OR = 1.15, 95% CI: 0.53-2.52; OR =
      1.13, 95% CI: 0.43-2.95; OR = 1.07, 95% CI: 0.67-1.72). Meanwhile, CRT had higher
      rates of grade 3 to 4 adverse events (nausea and vomiting, OR = 2.74, 95% CI:
      1.36-5.52; diarrhea, OR = 4.28, 95% CI: 1.16-15.71).The data are not sufficient
      to change from CT to CRT in the treatment of patients with LAPC and thus clinical
      discretion is required until more data is accumulated.

PMID- 30200164
TI  - Pattern of and clinicopathologic risk factors for lateral lymph node metastases
      in papillary thyroid carcinoma patients with lateral cervical lymphadenopathy.
AB  - The surgical extension of lateral neck dissection (LND) in papillary thyroid
      carcinoma (PTC) with clinical lateral lymph node metastases (LLNM) remains
      controversial. The aim of this study was to explore the pattern of and
      clinicopathologic risk factors for LLNM in PTC with clinical unilateral LND to
      determine the rational extent of therapeutic LND.This retrospective study
      reviewed the records of 246 consecutive patients with PTC who simultaneously
      underwent total thyroidectomy, bilateral central lymph node dissection, and
      unilateral therapeutic LND. The frequency and pattern of LLNM were
      analyzed.Grossly, LLNM were present in 80.9% of patients, and level II to V lymph
      node metastases (LNM) were present in 45.9%, 62.6%, 56.1%, and 11.8% patients,
      respectively. Superior tumor location, extrathyroidal extension, and ipsilateral,
      contralateral, and bilateral central LNM (CLNM) were independent risk factors for
      gross LLNM. Age >=45 years, superior lobe tumors, extrathyroidal extension, and
      ipsilateral and contralateral CLNM were independent risk factors for level II
      LNM. Age >=45 years, superior and middle lobe tumors, extrathyroidal extension,
      and ipsilateral CLNM were independent risk factors for level III LNM. Superior
      lobe tumors and ipsilateral, contralateral, and bilateral CLNM were independent
      risk factors for level IV LNM. Only contralateral CLNM was an independent risk
      factor for level V LNM.In PTC patients with clinical LLNM, the predominant sites
      of LLNM were levels II to IV and not level V. Therapeutic elective LND should
      include the lateral nodal levels associated with independent risk factors,
      especially superior tumors location and CLNM.

PMID- 30200165
TI  - Clinical efficacy of acupoint embedment in weight control: A systematic review
      and meta-analysis.
AB  - INTRODUCTION: Acupoint embedment, a modified acupuncture technique, is gaining
      its popularity in weight control in adult obesity or overweight nowadays. The
      objective of this study was to investigate the clinical efficacy of acupoint
      embedment in weight control of adult obesity or overweight by systematically
      assess available randomized controlled trials (RCTs) and analyze the integrated
      findings. A total of 529 literatures were initially searched from the databases.
      Five RCTs in assessing the effect of acupoint embedment versus sham control group
      were identified. RESULTS: A total of 219 subjects in the intervention group and
      206 subjects in the control group from 5 eligible studies were eventually
      included in this meta-analysis. Mean body mass index (BMI) decreased 0.94 kg/m
      (95% confidence interval [CI]: -1.56 to -0.32, P = .003) more in acupoint
      embedment group than the sham control group. Meanwhile, subjects received
      acupoint embedment had 2.97 kg (95% CI: -4.44 to -1.49, P < .0001) decrease in
      mean body weight more than in sham control group. Both parameters were
      statistically significant. Adverse events including bruise, soreness and cramp,
      patchy skin induration, erythema were reported, yet none involved hospitalization
      or mortality. Interestingly, stomach meridian and spleen meridian involved in all
      5 studies. CONCLUSION: This meta-analysis showed that acupoint embedment was more
      effective in weight control than the sham control group. Together with its
      convenience and low cost, acupoint embedment may be considered as an alternative
      treatment in weight control.

PMID- 30200166
TI  - Risk of diabetes mellitus in HIV-infected patients receiving highly active
      antiretroviral therapy: A nationwide population-based study.
AB  - Previous studies have shown that the incidence of diabetes mellitus (DM) has
      increased in human immunodeficiency virus (HIV)-infected patients with long-term
      exposure to highly active antiretroviral therapy (HAART). However, the factors
      associated with DM among HIV-infected patients in Asia remain unclear in the
      HAART era.A nationwide cohort studyData from Taiwan's National Health Insurance
      Research Database (NHIRD) between 2000 and 2010 were used to investigate the
      incidence of and factors associated with DM among HIV-infected patients.
      Propensity score matching was conducted to match 4797 patients receiving HAART
      (HAART cohort) with 4797 patients not receiving HAART (non-HAART cohort). HAART
      use was treated as a time-dependent variable in a Cox regression model.HAART
      cohort had a significantly higher 10-year incidence of DM (7.16%; 95% confidence
      interval [CI], 4.30%-10.03%) than non-HAART cohort (2.24%; 95% CI, 1.28%-3.20%)
      (P < .001). After adjusting for age, gender, and comorbidities, receiving HAART
      was associated with an increased incidence of DM, with a subdistribution hazard
      ratio (sHR) of 2.39 (95% CI, 1.65-3.45). Hypertension (sHR = 5.27; 95% CI, 3.21
      8.65), gout (sHR = 2.39; 95% CI, 1.38-4.16), and hepatitis C virus (HCV)
      infection (sHR = 2.43; 95% CI, 1.28-4.61) were significantly associated with a
      higher risk of DM. Sensitivity analyses showed exposure to HAART remained
      significantly associated with an increased risk of DM, particularly in those
      without pre-existing hypertension, gout, or HCV infection.Exposure to HAART
      increased the risk of DM in HIV-infected Taiwanese patients, particularly in
      those without pre-existing hypertension, gout, or HCV infection.

PMID- 30200167
TI  - The efficacy of oral versus intravenous tranexamic acid in reducing blood loss
      after primary total knee and hip arthroplasty: A meta-analysis.
AB  - BACKGROUND: Blood management after arthroplasties has become a serious problem.
      The objective is to perform a meta-analysis to compare the efficacy and safety
      between oral tranexamic acid (TXA) and intravenous TXA for blood management in
      total knee and hip arthroplasty. METHODS: We systematically searched randomized
      controlled trials (RCTs) from Medline, Embase, and the Cochrane Central Register
      of Controlled Trials (CENTRAL), Web of Science and Google scholar. Eligibility
      criteria: Patients: adult patients with end-stage joint osteoarthritis,
      rheumatoid arthritis, and osteonecrosis of the femoral head, who prepared for
      TJA; Interventions: The experiential group received the intravenous form of TXA;
      Comparisons: Oral form of TXA; Outcomes: Total blood loss, hemoglobin reduction,
      transfusion requirements, duration of hospitalization, and thrombotic
      complications including deep vein thrombosis (DVT) and pulmonary embolism (PE);
      Study design: Randomized control trials (RCTs) and non-RCT. Meta-analysis results
      were collected and analyzed by the software STATA 11.0. After testing for
      heterogeneity between studies, data were aggregated for random-effects models
      when necessary. RESULTS: Four RCTs and 2 non-RCTs were included in the meta
      analysis. The present meta-analysis revealed that there were no significant
      differences regarding total blood loss (WMD = -25.013, 95% CI: -51.002 to 0.977,
      P = .059), postoperative hemoglobin decline (WMD = -0.090, 95% CI: -0.205 to
      0.024, P = .122), or transfusion rate (RD = -0.039, 95% CI: -0.080 to 0.002, P =
      .062) between the 2 groups. CONCLUSION: Oral TXA shows comparable efficacy to
      that of the intravenous forms after total knee and hip arthroplasty. Due to the
      limited quality of evidence currently available, higher quality RCTs is
      necessary.

PMID- 30200168
TI  - Sepsis as an important risk factor for gastrointestinal bleeding in acute
      coronary syndrome patients: Two case reports.
AB  - RATIONALE: Sepsis is a common stressor that may decrease microcirculation in the
      gastrointestinal tract in patients and increase the gastrointestinal bleeding
      risk of stress-related mucosal disease. However, the CRUSADE (Can Rapid Risk
      Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early
      Implementation of the ACC/AHA Guidelines) bleeding risk score, recommended by
      authoritative guidelines for acute coronary syndrome (ACS), does not include
      sepsis as a bleeding risk factor. PATIENT CONCERNS: The 2 cases were about ACS
      with hemorrhagic complications. The first patient was an 88-year-old man with
      hypertension, gallstones, hepatic cysts, and chest pain; the second one was a 79
      year-old man with chest pain and hypertension. These 2 ACS patients had no
      bleeding on admission; however, both patients suffered apparent gastrointestinal
      bleeding immediately after the development of sepsis or severe sepsis. DIAGNOSES:
      Both patients were diagnosed as ACS with sepsis. INTERVENTIONS: The first ACS
      patient had no use of proton pump inhibitors (PPIs) for prophylaxis prior to the
      diagnosis of sepsis. The second one was administered PPIs at standard oral doses.
      OUTCOMES: The first patient suffered from gastrointestinal bleeding immediately
      after the onset of sepsis. And oral PPIs failed to prevent upper gastrointestinal
      bleeding for the second patient, when severe sepsis developed. However, the
      second patient's gastrointestinal hemorrhage gradually stopped immediately after
      high doses of PPIs were administered intravenously, rather than orally. When
      sepsis developed again, the second patient also had no recurrent gastrointestinal
      bleeding under the protection of PPIs at standard oral doses. LESSONS: Our report
      suggests that sepsis may be an important bleeding risk factor for ACS patients,
      and the reasonable use of PPIs to prevent gastrointestinal bleeding could be
      vital for ACS patients complicated with sepsis.

PMID- 30200169
TI  - Long period of relative quiescence in distal-type epithelioid sarcoma of the
      forearm with recurrence after surgery: A case report.
AB  - BACKGROUND: Epithelioid sarcoma (ES) is a rare malignant mesenchymal tumor that
      only accounts for 0.6% to 1.0% of all cases of sarcomas. ES with a relative
      quiescent state of more than 10 years is extremely rare.Here, we present a rare
      case of ES in the forearm of a 17-year-old girl. The patient had a congenital
      mass in her forearm that measured approximately 1cm; it grew rapidly starting 5
      years ago. The mass was not treated until last year when she underwent the first
      surgery. The mass was located in the middle and lower part of the left forearm
      and involved the dorsal muscle group, intermuscular space, and subcutaneous
      tissues without clear boundaries.The patient underwent surgery, and the tumor
      recurred twice within 1 year postoperatively. METHODS: The tumor samples were
      examined via hematoxylin-eosin (HE) and immunohistochemistry staining. RESULTS:
      Histopathologically, the tumor comprised large polygonal epithelioid cells with
      abundant eosinophilic cytoplasm arranged in cell nests. Central necrosis and
      focal myxoid change could be seen in the tumor tissues. Immunostaining showed
      that the tumor cells were positive for CD34, CK, EMA, and vimentin but negative
      for CD31, S-100, and INI-1. CONCLUSION: Based on these findings, the tumor was
      diagnosed as ES of distal form. Distal-type ES could have a long period of
      relative quiescence, after which it could grow rapidly and relapse multiple times
      over a short duration.

PMID- 30200170
TI  - Midregional pro-atrial natriuretic peptide is a superior biomarker to N-terminal
      pro-B-type natriuretic peptide in the diagnosis of heart failure patients with
      preserved ejection fraction.
AB  - OBJECTIVES: To explore that if mid-regional sequence of pro-A-type natriuretic
      peptide (MR-proANP) may have a good value of diagnosis in heart failure with
      preserved ejection fraction (HFpEF) compared with N-terminal pro-B-type
      natriuretic peptide (NT-proBNP). METHODS: Participants with cardiovascular
      disease who were enrolled in this study were divided into the nonheart failure
      (non-HF) group (n = 75), HFpEF group (n = 65), and HF with reduced ejection
      fraction (HFrEF) group (n = 50). The MR-proANP and NT-proBNP levels in plasma
      from all patients were measured by enzyme-linked immunosorbent assay. RESULTS:
      The plasma levels of MR-proANP and NT-proBNP in HFpEF and HFrEF groups were
      higher than those in non-HF group (P < .05). MR-proANP levels were significantly
      different (P < .05) in different New York Heart Association class patients with
      HFpEF. In the diagnostic analysis area under the curve of MR-proANP (0.844) was
      higher than that of NT-proBNP (0.518, P < .001). The left atrial volume index in
      the HFrEF group was higher than HFpEF group (P < .05); however, both of these
      groups had a higher index than non-HF group (P < .05). CONCLUSION: Results
      indicated that MR-proANP may be more sensitive and specific than NT-proBNP in
      diagnosing HFpEF. It may be used as a potential diagnostic biomarker in patients
      with HFpEF.

PMID- 30200171
TI  - Risk factors for HIV infection among 15 to 25-year-old rural unmarried Yi
      adolescents in an ethnic minority region of China.
AB  - We aimed to analyze factors related to human immunodeficiency virus (HIV)
      infection among 15 to 25-year-old rural unmarried Yi adolescents in Liangshan Yi
      Autonomous Prefecture from 2011 to 2016, and to investigate the relationship
      among the HIV-related risk factors.Three sites (Butuo, Zhaojue, and Ganluo
      counties) with a Yi population were selected from 2011 to 2016 in Liangshan
      prefecture. We used questionnaires to investigate demographic and behavioral
      characteristics and performed HIV testing. Logistic regression analysis and
      multiple correspondence analysis (MCA) were used to analyze the data.A total of
      6311 qualified rural unmarried Yi adolescents were involved in this study, with
      an HIV infection rate of 4.18% (264/6311). Logistic regression analysis indicated
      that males (OR = 1.56, 95% CI = 1.17-2.08), illiteracy (OR = 2.70, 95% CI = 1.79
      4.08), primary school education or below (OR = 1.62, 95% CI = 1.12-2.36), history
      of out-migrating for work (OR = 1.58, 95% CI = 1.18-2.13), and injecting drug
      user (IDU) (OR = 6.42, 95% CI = 3.06-13.46) contributed to the risk of HIV
      infection. MCA revealed a strong interrelationship between the following risk
      factors and HIV infection: aged 23 to 25 years, IDU, history of out-migrating for
      work, and ever having sexual behaviors.HIV infection among 15 to 25-year-old
      rural unmarried Yi adolescents in Liangshan is a serious issue. MCA and logistic
      regression analysis can be used to assess the relationship between risk factors
      for HIV infection.

PMID- 30200172
TI  - Relationship between dyslipidemia and diabetic retinopathy: A systematic review
      and meta-analysis.
AB  - BACKGROUND: The association between serum lipids and diabetic retinopathy (DR)
      was controversial. Therefore, we performed a meta-analysis to evaluate the
      relationship between triglycerides (TG), serum total cholesterol (TC), high
      density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol
      (LDL-C), and DR. METHODS: A systematic review and meta-analysis of observational
      studies was carried out to explore the association between serum lipids and DR.
      Studies related were initially indentified by searching PubMed, Cochrane Library,
      and Elsevier databases through June, 2017. Then a manual retrieval was also
      performed. RevMan 5.3 software was used to calculate the pooled mean differences
      (MDs) and related 95% confidence intervals (CIs). To test the stability of the
      final results, a sensitivity analysis was also performed. RESULTS: A total of 7
      studies were included in this meta-analysis. When compared with the controls, the
      DR cases did not show significantly higher TG levels (MD 9.18 mg/dL, 95%CI -4.14
      to 22.49, P = .18), higher TC levels (MD 3.77 mg/dL, 95%CI: -2.45 to 9.98, P =
      .24), as well as lower HDL-C levels (MD -1.14 mg/dL, 95%CI: -2.43 to 0.15, P =
      .08). But slightly higher LDL-C levels were observed (MD 3.74 mg/dL, 95%CI: 0.13
      7.35, P = .04). In addition, whether serum lipids involved in the progression of
      DR were relatively unexplored, but fenofibrate was confirmed to benefit the DR
      cases. CONCLUSIONS: Based on recent published data, we did not find obvious
      differences in TG, TC, and HDL-C levels between patients with DR and without DR.
      However, slightly higher LDL-C levels were observed in the DR cases.

PMID- 30200173
TI  - The prognostic efficacy of the 8th edition UICC TNM classifications for gastric
      cancer in Chinese patients: A study based on follow-up system of nursing
      department.
AB  - This study aimed to analyze the applicability of the Union for International
      Cancer Control (UICC) tumor-node-metastasis (TNM) classification 8th edition for
      Chinese patients with gastric cancer.A review of all inpatient and outpatient
      records of patients with gastric cancer was conducted in the First Affiliated
      Hospital of China Medical University and Liaoning Cancer Hospital and Institute.
      All patients who met the inclusion criteria and were seen from January 1980
      through December 2009 were included in the study. The primary outcome was 5-year
      survival, which was analyzed according to the decade of diagnosis and TNM
      classifications.Two thousand five hundred fifty-four patients were enrolled in
      this study. When classified according to the UICC TNM classification of gastric
      cancer 8th edition, the prognoses of patients with stage IIIB (n = 250) and stage
      IIIC (n = 101) disease were not significantly different (P = .332). However, if
      T4aN2 patients were classified as having stage IIIB disease, and T4bN2 and T4aN3a
      patients were classified as having stage IIIC disease, the prognoses of stage
      IIIB (n = 221) and stage IIIC (n = 172) patients were significantly different (P
      = .03).Classifying T4bN0 patients as having stage IIIB disease, and T4bN2 and
      T4aN3a patients as having stage IIIC disease according to the 8th edition of UICC
      gastric cancer TNM classifications better stratified Chinese patients and
      predicted prognoses.

PMID- 30200174
TI  - The association of serum 25-OH vitamin D with asthma in Saudi adults.
AB  - The study aimed to assess the differences and associations of serum 25 (OH)D
      levels in Saudi adults with and without asthma. A total of 1070 Saudi adults aged
      22 to 28 years (359 with known asthma and 711 matched nonasthmatic controls) were
      selected randomly from the Riyadh Cohort, Saudi Arabia. Serum 25(OH)D serum
      levels were measured. Asthma diagnosis was taken from questionnaires. In all
      participants, 359 (33.6%) were known asthmatic and 711 (66.5%) were nonasthmatic.
      The overall incidence of vitamin D deficiency (serum 25(OH)D <25 nmol/L) was
      29.6% in controls and 35.6% in asthma group (P = .01). The asthma group have a
      significantly lower serum 25(OH)D than the control group (P = .01) but lost
      significance after adjusting for age, body mass index (BMI), and sex.
      Nonasthmatic and asthmatic females had a higher incidence of vitamin D deficiency
      (33% and 46%) than nonasthmatic and asthmatic males (17% and 33%). Vitamin D
      deficiency is significantly high among Saudi adults with asthma, but more so
      among women. Whether vitamin D deficiency exacerbates asthma attack remains to be
      proven in this population.

PMID- 30200175
TI  - Combination of oral nonabsorbable and intravenous antibiotics versus intravenous
      antibiotics alone in the prevention of surgical site infections after elective
      colorectal surgery in pediatric patients: A retrospective study.
AB  - We conducted this study to compare the effectiveness of combined oral
      nonabsorbable and intravenous antibiotics versus intravenous antibiotics alone in
      reducing the incidence of surgical site infections following elective colorectal
      surgery in pediatric patients.Between January 2010 and December 2016, patients
      from 0 to 14 who underwent elective colorectal surgery were retrospectively
      analyzed. Based on intravenous antibiotics with and without oral antibiotics, the
      patients were grouped as OA group (combination of oral nonabsorbable and
      intravenous antibiotics) or A group (the intravenous antibiotics alone). Neomycin
      combined with erythromycin was used in OA group. The data collected included
      demographic data, diagnosis, procedure being performed, operative time, time to
      first stool, time to removal of the nasogastric tube, time to full enteral feeds,
      hospital length of stay, and prophylactic antibiotics (days +/- standard
      deviation). The main outcome was the rate of postoperative infectious
      complications, such as wound infection, anastomotic leak, and intra-abdominal
      abscess formation.A total of 564 children who underwent elective colorectal
      surgery were enrolled which consist of OA group (combination of oral
      nonabsorbable and intravenous antibiotics) and A group (the intravenous
      antibiotics alone), the number of the former one was 216 and the latter one was
      348. Postoperative complications were similar in both groups of patients. In the
      OA group, we observed 5 anastomotic leak, 6 wound infections, and 5 intra
      abdominal abscesses. In the A group, we observed 13 anastomotic leak, 9 wound
      infections, and 11 intra-abdominal abscesses. Analysis with Fisher exact test
      revealed no statistically significant difference in the incidence of wound
      infection, anastomotic leak, and intra-abdominal abscess between the 2 groups.The
      results of our study suggest that omitting oral nonabsorbable antibiotics before
      elective colorectal surgery in infants and children carries no increased risk of
      infectious or anastomotic complications.

PMID- 30200176
TI  - Research on the Crushing Process of PELE Casing Material Based on the Crack
      Softening Algorithm and Stochastic Failure Algorithm.
AB  - In order to more realistically reflect the penetrating and crushing process of a
      PELE (Penetration with Enhanced Lateral Efficiency) projectile, the stochastic
      failure algorithm and crack-softening algorithm were added to the corresponding
      material in this paper. According to the theoretical analysis of the two
      algorithms, the material failure parameters (stochastic constant gamma, fracture
      energy Gf, and tensile strength sigmaT) were determined. Then, four sets of
      simulation conditions ((a) no crack softening, (b) no stochastic failure, (c) no
      crack softening and no stochastic failure, and (d) crack softening and stochastic
      failure) were designed to qualitatively describe the influences of the failure
      algorithms, which were simulated by the finite element analysis software AUTODYN.
      The qualitative comparison results indicate that the simulation results after
      adding the two algorithms were closer to the actual situation. Finally, ten
      groups of simulation conditions were designed to quantitatively analyze the
      coincidence degree between the simulation results and the experimental results by
      means of two parameters: the residual velocity of the projectile and the maximum
      radial velocity of fragments. The results show that the simulation results
      coincide well with the experimental results and the errors were small. Therefore,
      the ideas proposed in this paper are scientific, and the conclusions obtained can
      provide guidance for engineering research.

PMID- 30200177
TI  - Evaluation of Eosin-Methylene Blue as a Photosensitizer for Larval Control of
      Aedes aegypti by a Photodynamic Process.
AB  - Aedes aegypti (Ae. aegypti) is a competent vector for transmitting important
      viral diseases such as yellow fever, dengue, chikungunya, and Zika. Several
      strategies have been applied to avoid Ae. aegypti proliferation by using
      environmental management, biological, and chemical approaches. However, the
      development of new methods for effective control of the insect vector population
      is still needed. Photodynamic control is an alternative way to control the vector
      population by using a physical approach based on the larval phototoxicity of a
      photosensitizer. In this context, the present study evaluated the use of eosin
      methylene blue (EMB) as a new photosensitizer for photodynamic control of Ae.
      aegypti larval populations. The photodynamic assays were performed submitting Ae.
      aegypti third-instar larvae to different EMB concentrations (0.0, 0.5, 1.0, 5.0,
      10.0, 50.0, and 100.0 ug mL-1) in combination of three different light doses
      (24.3, 48.6, and 97.2 J cm-2) under either white-light radiation from RGB LEDs or
      sunlight. The results demonstrated that EMB presented a rapid internalization
      into the larvae and was phototoxic. The photodynamic action induced 100% of
      larval mortality after about 40 min of sunlight irradiation even using low EMB
      concentration (0.5 ug mL-1). The findings reveal EMB as an effective photoactive
      compound to control larval populations of Ae. aegypti by photodynamic process
      induced by either sunlight or white-light from RGB LEDs.

PMID- 30200178
TI  - Two Different Strategies to Enhance Osseointegration in Porous Titanium:
      Inorganic Thermo-Chemical Treatment Versus Organic Coating by Peptide Adsorption.
AB  - In this study, highly-interconnected porous titanium implants were produced by
      powder sintering with different porous diameters and open interconnectivity. The
      actual foams were produced using high cost technologies: Chemical Vapor
      Deposition (CVD), Physical Vapor Deposition (PVD), and spark plasma sintering,
      and the porosity and/or interconnection was not optimized. The aim was to
      generate a bioactive surface on foams using two different strategies, based on
      inorganic thermo-chemical treatment and organic coating by peptide adsorption, to
      enhance osseointegration. Porosity was produced using NaCl as a space holder and
      polyethyleneglicol as a binder phase. Static and fatigue tests were performed in
      order to determine mechanical behaviors. Surface bioactivation was performed
      using a thermo-chemical treatment or by chemical adsorption with peptides.
      Osteoblast-like cells were cultured and cytotoxicity was measured. Bioactivated
      scaffolds and a control were implanted in the tibiae of rabbits.
      Histomorphometric evaluation was performed at 4 weeks after implantation.
      Interconnected porosity was 53% with an average diameter of 210 um and an elastic
      modulus of around 1 GPa with good mechanical properties. The samples presented
      cell survival values close to 100% of viability. Newly formed bone was observed
      inside macropores, through interconnected porosity, and on the implant surface.
      Successful bone colonization of inner structure (40%) suggested good
      osteoconductive capability of the implant. Bioactivated foams showed better
      results than non-treated ones, suggesting both bioactivation strategies induce
      osteointegration capability.

PMID- 30200180
TI  - Evaluation of Nutritional and Technological Attributes of Whole Wheat Based Bread
      Fortified with Chia Flour.
AB  - The aim of this study was to investigate and compare the effect of wheat bread
      fortification with varied levels (2%, 4%, and 6%) of chia seed powder (full fat)
      and cakes (defatted, residue after oil extraction). Chia flour was added to whole
      wheat bread rich in vital wheat gluten for the first time. The breadcrumbs were
      assessed for their antioxidant activity, nutritional content, textural
      properties, color, and sensory profiles. The addition of chia seed powder,
      particularly in high levels, was more effective in improving antioxidant activity
      compared to bread fortified with chia cakes. Bread supplementation with chia
      flour improves its nutritional value, especially in the case of chia cakes. A
      higher moisture content and lower hardness were observed after bread
      fortification, the influence was more evident with the defatted cake than with
      seed powder. Fortification with chia flour led to darker breads without
      significantly affecting their global acceptability. However, the fortified bread
      showed better values than control in terms of sensory profile. These results
      suggest that the addition of chia seed powder and defatted cake can enhance the
      overall whole wheat bread quality. Our results also highlight that bread making
      could be an unconventional alternative for the exploitation of defatted chia
      seed.

PMID- 30200179
TI  - The Future of Influenza Vaccines: A Historical and Clinical Perspective.
AB  - For centuries, the development of vaccines to prevent infectious disease was an
      empirical process. From smallpox variolation in Song dynasty China, through the
      polysaccharide capsule vaccines developed in the 1970s, vaccines were made either
      from the pathogen itself, treated in some way to render it attenuated or non
      infectious, or from a closely related non-pathogenic strain. In recent decades,
      new scientific knowledge and technologies have enabled rational vaccine design in
      a way that was unimaginable before. However, vaccines optimal against some
      infectious diseases, influenza among them, have remained elusive. This review
      will highlight the challenges that influenza viruses pose for rational vaccine
      design. In particular, it will consider the clinically beneficial endpoints,
      beyond complete sterilizing immunity, that have been achieved with vaccines
      against other infectious diseases, as well as the barriers to achieving similar
      success against influenza.

PMID- 30200181
TI  - Discovery of High-Affinity Cannabinoid Receptors Ligands through a 3D-QSAR
      Ushered by Scaffold-Hopping Analysis.
AB  - Two 3D quantitative structure-activity relationships (3D-QSAR) models for
      predicting Cannabinoid receptor 1 and 2 (CB1 and CB2) ligands have been produced
      by way of creating a practical tool for the drug-design and optimization of CB1
      and CB2 ligands. A set of 312 molecules have been used to build the model for the
      CB1 receptor, and a set of 187 molecules for the CB2 receptor. All of the
      molecules were recovered from the literature among those possessing measured Ki
      values, and Forge was used as software. The present model shows high and robust
      predictive potential, confirmed by the quality of the statistical analysis, and
      an adequate descriptive capability. A visual understanding of the hydrophobic,
      electrostatic, and shaping features highlighting the principal interactions for
      the CB1 and CB2 ligands was achieved with the construction of 3D maps. The
      predictive capabilities of the model were then used for a scaffold-hopping study
      of two selected compounds, with the generation of a library of new compounds with
      high affinity for the two receptors. Herein, we report two new 3D-QSAR models
      that comprehend a large number of chemically different CB1 and CB2 ligands and
      well account for the individual ligand affinities. These features will facilitate
      the recognition of new potent and selective molecules for CB1 and CB2 receptors.

PMID- 30200182
TI  - The Potential Role of Genetic Markers in Talent Identification and Athlete
      Assessment in Elite Sport.
AB  - In elite sporting codes, the identification and promotion of future athletes into
      specialised talent pathways is heavily reliant upon objective physical,
      technical, and tactical characteristics, in addition to subjective coach
      assessments. Despite the availability of a plethora of assessments, the
      dependence on subjective forms of identification remain commonplace in most
      sporting codes. More recently, genetic markers, including several single
      nucleotide polymorphisms (SNPs), have been correlated with enhanced aerobic
      capacity, strength, and an overall increase in athletic ability. In this review,
      we discuss the effects of a number of candidate genes on athletic performance,
      across single-skilled and multifaceted sporting codes, and propose additional
      markers for the identification of motor skill acquisition and learning. While
      displaying some inconsistencies, both the ACE and ACTN3 polymorphisms appear to
      be more prevalent in strength and endurance sporting teams, and have been found
      to correlate to physical assessments. More recently, a number of polymorphisms
      reportedly correlating to athlete performance have gained attention, however
      inconsistent research design and varying sports make it difficult to ascertain
      the relevance to the wider sporting population. In elucidating the role of
      genetic markers in athleticism, existing talent identification protocols may
      significantly improve-and ultimately enable-targeted resourcing in junior talent
      pathways.

PMID- 30200184
TI  - Triplex Real-Time PCR without DNA Extraction for the Monitoring of Meningococcal
      Disease.
AB  - Detection of Neisseria meningitidis has become less time- and resource-intensive
      with a monoplex direct real-time PCR (drt-PCR) to amplify genes from clinical
      specimens without DNA extraction. To further improve efficiency, we evaluated two
      triplex drt-PCR assays for the detection of meningococcal serogroups AWX and BCY.
      The sensitivity and specificity of the triplex assays were assessed using 228
      cerebrospinal fluid (CSF) specimens from meningitis patients and compared to the
      monoplex for six serogroups. The lower limit of detection range for six serogroup
      specific drt-PCR assays was 178-5264 CFU/mL by monoplex and 68-2221 CFU/mL by
      triplex. The triplex and monoplex showed 100% agreement for six serogroups and
      the triplex assays achieved similar sensitivity and specificity estimates as the
      monoplex drt-PCR assays. Our triplex method reduces the time and cost of
      processing CSF specimens by characterizing six serogroups with only two assays,
      which is particularly important for testing large numbers of specimens for N.
      meningitidis surveillance.

PMID- 30200183
TI  - The Enhanced Interactive Physical and Cognitive Exercise System (iPACESTM v2.0):
      Pilot Clinical Trial of an In-Home iPad-Based Neuro-Exergame for Mild Cognitive
      Impairment (MCI).
AB  - Given increasing longevity worldwide, older adults and caregivers are seeking
      ways to curb cognitive decline especially for those with mild cognitive
      impairment (MCI, now mild neurocognitive disorder, mNCD, Diagnostic and
      Statistical Manual of Mental Disorders, 5th ed. (DSM-V). This quasi-experimental,
      within-subjects pilot clinical trial was designed to replicate and extend the
      study of cognitive benefits for MCI by improving upon our prior interactive
      Physical and Cognitive Exercise Study (iPACESTM v1.0) by increasing the usability
      of the neuro-exergame and exploring possible underlying neurobiological
      mechanisms. Older adults were enrolled in a three-month, in-home trial of a
      portable neuro-exergame (iPACESTM v2.0) where participants pedaled and steered
      along a virtual bike path (Memory LaneTM). Neuropsychological function was
      assessed at baseline after component familiarization intervals (e.g., two weeks
      of exercise-only, game-only, etc.) and after three months of interactive neuro
      exergame intervention. Fourteen participants were enrolled in the study and seven
      completed the final evaluation. Intent-to-treat analyses were conducted with
      imputed missing data (total n = 14). Significant improvement in executive
      function (Stroop) was found (d = 0.68, p = 0.02) only. Changes in salivary
      biomarkers (cortisol and insulin-like growth factor 1; IGF-1) were significantly
      associated with improved cognition. Further research is needed, but pilot data
      suggest that a portable in-home neuro-exergame may be an additional, practical
      tool to fight back against cognitive decline and dementia.

PMID- 30200186
TI  - Comparative Analysis of Chemical Composition, Anti-Inflammatory Activity and
      Antitumor Activity in Essential Oils from Siegesbeckiaorientalis, S. glabrescens
      and S. pubescens with an ITS Sequence Analysis.
AB  - Herba Siegesbeckiae (HS), derived from the aerial parts of three plants,
      Siegesbeckia orientalis (SO), S. glabrescens (SG), and S. pubescens (SP), has
      been used for the treatment of inflammatory diseases in China for centuries. In
      the present study, hydrodistillation was applied to extract essential oils from
      dried SO, SG, and SP aerial parts, and chemical composition analysis by gas
      chromatography-mass spectrometry (GC-MS) led to the identification of a total of
      148 compounds (56 in SO, 62 in SG, and 59 in SP). The main components in the
      essential oils of SO, SG, and SP differed significantly. In vitro anti
      inflammatory activity assays showed that SP essential oils (IC50, 0.97 MUg/mL)
      significantly reduced the ability of lipopolysaccharide (LPS)-stimulated RAW264.7
      macrophages to release NO, and the SO essential oil (IC50, 14.99 MUg/mL) was
      better than the others at inhibiting the LPS-induced release of cytokine IL-6.
      Furthermore, the essential oils exhibited antitumor activities (IC50, 37.72
      123.16 MUg/mL) against Hep3B (liver) and Hela (cervical) cells. Linear regression
      analysis showed that, caryophyllene oxide peak area percentages showed remarkably
      high negative correlation coefficients with IC50 values of Hep3B and Hela
      cytotoxicity, which suggested the contribution of this compound on the cancer
      cell cytotoxicity of three essential oils. Finally, the ITS1-5.8S-ITS2 region was
      amplified and sequenced in order to generate genomic reference sequences for each
      plant. These can be used to identify the origins of the plants, and will assist
      other research studies related to these three plants.

PMID- 30200185
TI  - Nutritional Quality during Development Alters Insulin-Like Peptides' Expression
      and Physiology of the Adult Yellow Fever Mosquito, Aedes aegypti.
AB  - Mosquitoes have distinct developmental and adult life history, and the vectorial
      capacity of females has been shown to be affected by the larval nutritional
      environment. However, little is known about the effect of developmental nutrition
      on insulin-signaling and nutrient storage. In this study, we used Aedes aegypti,
      the yellow fever mosquito, to determine whether larval nutrition affects insulin
      gene expression. We also determined the traits regulated by insulin signaling,
      such as stored-nutrient levels and fecundity. We raised mosquito larvae on two
      different diets, containing either high protein or high carbohydrates.
      Development on a high-carbohydrate diet resulted in several life-history
      phenotypes indicative of suboptimal conditions, including increased developmental
      time and decreased fecundity. Additionally, our data showed that insulin
      transcript levels are affected by a high-carbohydrate diet during development.
      Females, not males, reared on high-carbohydrate diets had much higher transcript
      levels of insulin-like peptide 3 (ILP3), a mosquito equivalent of human insulin,
      and these females more readily converted sugar meals into lipids. We also found
      that AaILP4, not AaILP3, transcript levels were much higher in the males after a
      sugar meal, suggesting sex-specific differences in the insulin-signaling pathway.
      Our findings suggest a conserved mechanism of carbohydrate-mediated
      hyperinsulinemia in animals.

PMID- 30200187
TI  - The Use of Intravenous Vitamin C as a Supportive Therapy for a Patient with
      Glioblastoma Multiforme.
AB  - Glioblastoma multiforme is a high grade malignant brain tumour with a poor
      prognosis. Here we report the case of a woman with glioblastoma who lived for
      over four years from diagnosis (median survival 12 months and 2% survival for
      three years), experiencing good quality of life for most of that time. She
      underwent initial debulking craniotomy, radiotherapy and chemotherapy, as well as
      having intravenous vitamin C infusions 2-3 times weekly over the four years from
      diagnosis. Her progress was monitored by blood tests, regular computerised
      tomography (CT) and magnetic resonance imaging (MRI) scans, clinical reviews and
      European Organization for the Research and Treatment of Cancer quality of life
      questionnaires (EORTC QLQ C30). Our case report highlights the benefits of
      intravenous vitamin C as a supportive therapy for patients with glioblastoma.

PMID- 30200188
TI  - Towards an Efficient One-Class Classifier for Mobile Devices and Wearable Sensors
      on the Context of Personal Risk Detection.
AB  - In this work, we present a first step towards an efficient one-class classifier
      well suited for mobile devices to be implemented as part of a user application
      coupled with wearable sensors in the context of personal risk detection. We
      compared one-class Support Vector Machine (ocSVM) and OCKRA (One-Class K-means
      with Randomly-projected features Algorithm). Both classifiers were tested using
      four versions of the publicly available PRIDE (Personal RIsk DEtection) dataset.
      The first version is the original PRIDE dataset, which is based only on time
      domain features. We created a second version that is simply an extension of the
      original dataset with new attributes in the frequency domain. The other two
      datasets are a subset of these two versions, after a feature selection procedure
      based on a correlation matrix analysis followed by a Principal Component
      Analysis. All experiments were focused on the performance of the classifiers as
      well as on the execution time during the training and classification processes.
      Therefore, our goal in this work is twofold: we aim at reducing execution time
      but at the same time maintaining a good classification performance. Our results
      show that OCKRA achieved on average, 89.1% of Area Under the Curve (AUC) using
      the full set of features and 83.7% when trained using a subset of them.
      Furthermore, regarding execution time, OCKRA reports in the best case a 33.1%
      gain when using a subset of the feature vector, instead of the full set of
      features. These results are better than those reported by ocSVM, in which case,
      even though the AUCs are very close to each other, execution times are
      significantly higher in all cases, for example, more than 20 h versus less than
      an hour in the worst-case scenario. Having in mind the trade-off between
      classification performance and efficiency, our results support the choice of
      OCKRA as our best candidate so far for a mobile implementation where less
      processing and memory resources are at hand. OCKRA reports a very encouraging
      speed-up without sacrificing the classifier performance when using the PRIDE
      dataset based only on time-domain attributes after a feature selection procedure.

PMID- 30200190
TI  - Developments in the Research Base on Reducing Exposure to Second-Hand Smoke.

PMID- 30200189
TI  - Dihydromyricetin as a Functional Additive to Enhance Antioxidant Capacity and
      Inhibit the Formation of Thermally Induced Food Toxicants in a Cookie Model.
AB  - Recently, there is a growing interest in fortifying food products with flavonoids
      to enhance health benefits. Naringenin, naringin, hesperetin, and
      dihydromyricetin are four typical flavonoids constituting a natural part of our
      diet. In the present work, they were fortified into a chia oil cookie model to
      evaluate their thermal stability during baking as well as their impact on
      antioxidant capacity and toxicant formation. Among them dihydromyricetin was the
      most unstable one (only 36.1% of which was left after baking at 180  degrees C
      for 20 min) and led to a loss of brightness in cookie. However, the antioxidant
      capacity of cookie fortified with dihydromyricetin was significantly enhanced
      compared with untreated cookie; on the other hand, dihydromyricetin showed the
      strongest effect to attenuate lipid and protein oxidation as well as decrease the
      level of fluorescent advanced glycation endproducts and carboxymethyl lysine in
      cookie model. Overall, among the four selected flavonoids, dihydromyricetin might
      be the most promising functional bakery additive enhancing the antioxidant
      capacity while decreasing the formation of toxicants.

PMID- 30200191
TI  - Water Dispersible Few-Layer Graphene Stabilized by a Novel Pyrene Derivative at
      Micromolar Concentration.
AB  - The search for graphene or few-layer graphene production methods that are simple,
      allow mass production, and yield good quality material continues to provoke
      intense investigation. The present work contributes to this investigation through
      the study of the aqueous exfoliation of four types of graphene sources, which are
      namely graphite and graphite nanoflakes with different morphologies and
      geographical origins. The exfoliation was achieved in an aqueous solution of a
      soluble pyrene derivative that was synthesized to achieve maximum interaction
      with the graphene surface at low concentration (5 * 10-5 M). The yield of bilayer
      and few-layer graphene obtained was quantified by Raman spectroscopic analysis,
      and the adsorption of the pyrene derivative on the graphene surface was studied
      by thermogravimetric analysis and X-ray diffraction. The whole procedure was
      rationalized with the help of molecular modeling.

PMID- 30200192
TI  - FSCPX, a Chemical Widely Used as an Irreversible A1 Adenosine Receptor
      Antagonist, Modifies the Effect of NBTI, a Nucleoside Transport Inhibitor, by
      Reducing the Interstitial Adenosine Level in the Guinea Pig Atrium.
AB  - Based on in silico results, recently we have assumed that FSCPX, an irreversible
      A1 adenosine receptor antagonist, inhibits the action of NBTI that is apparent on
      E/c curves of adenosine receptor agonists. As a mechanism for this unexpected
      effect, we hypothesized that FSCPX might modify the equilibrative and NBTI
      sensitive nucleoside transporter (ENT1) in a way that allows ENT1 to transport
      adenosine but impedes NBTI to inhibit this transport. This assumption implies
      that our method developed to estimate receptor reserve for agonists with short
      half-life such as adenosine, in its original form, overestimates the receptor
      reserve. In this study, therefore, our goals were to experimentally test our
      assumption on this effect of FSCPX, to improve our receptor reserve-estimating
      method and then to compare the original and improved forms of this method. Thus,
      we improved our method and assessed the receptor reserve for the direct negative
      inotropic effect of adenosine with both forms of this method in guinea pig atria.
      We have found that FSCPX inhibits the effects of NBTI that are mediated by
      increasing the interstitial concentration of adenosine of endogenous (but not
      exogenous) origin. As a mechanism for this action of FSCPX, inhibition of enzymes
      participating in the interstitial adenosine production can be hypothesized, while
      modification of ENT1 can be excluded. Furthermore, we have shown that, in
      comparison with the improved form, the original version of our method
      overestimates receptor reserve but only to a small extent. Nevertheless, use of
      the improved form is recommended in the future.

PMID- 30200193
TI  - Favorable Effects of a Ketogenic Diet on Physical Function, Perceived Energy, and
      Food Cravings in Women with Ovarian or Endometrial Cancer: A Randomized,
      Controlled Trial.
AB  - Ketogenic diets (KDs) are gaining attention as a potential adjuvant therapy for
      cancer, but data are limited for KDs' effects on quality of life. We hypothesized
      that the KD would (1) improve mental and physical function, including energy
      levels, (2) reduce hunger, and (3) diminish sweet and starchy food cravings in
      women with ovarian or endometrial cancer. Participants were randomized to a KD
      (70:25:5 energy from fat, protein, and carbohydrate) or the American Cancer
      Society diet (ACS: high-fiber, lower-fat). Questionnaires were administered at
      baseline and after 12 weeks on the assigned diet to assess changes in mental and
      physical health, perceived energy, appetite, and food cravings. We assessed both
      between-group differences and within-group changes using ANCOVA and paired t
      tests, respectively. After 12 weeks, there was a significant between-group
      difference in adjusted physical function scores (p < 0.05), and KD participants
      not receiving chemotherapy reported a significant within-group reduction in
      fatigue (p < 0.05). There were no significant between-group differences in mental
      function, hunger, or appetite. There was a significant between-group difference
      in adjusted cravings for starchy foods and fast food fats at 12 weeks (p < 0.05
      for both), with the KD group demonstrating less frequent cravings than the ACS.
      In conclusion, in women with ovarian or endometrial cancer, a KD does not
      negatively affect quality of life and in fact may improve physical function,
      increase energy, and diminish specific food cravings. This trial was registered
      at ClinicalTrials.gov as NCT03171506.

PMID- 30200194
TI  - Assessing Animal Welfare in Animal-Visitor Interactions in Zoos and Other
      Facilities. A Pilot Study Involving Giraffes.
AB  - In recent years, awareness of the controversial aspects connected with wild
      animal-visitor interactions (AVIs) in zoos and other facilities has increased due
      to cultural changes. Therefore, the need to apply transparent procedures to
      evaluate AVIs programs in zoos and similar facilities has also increased. This
      study presents results of animal welfare's assessment of a pilot test of a
      protocol based on six steps that aim to explore and assess the overall value of
      AVIs considering the impact both on animals and visitors. In the present paper,
      we discuss the multifaceted approach to animal welfare assessment during animal
      visitor interactions, combining quantitative behavioural observations/analysis
      and a welfare risk-assessment procedure, which forms the basis of the six-step
      protocol. Pilot testing of said approach to animal welfare assessment involved
      giraffes (Giraffa camelopardalis) in an Italian zoo. No change in behaviour,
      suggestive of an increased welfare risk to the animals, was found. The risk
      analysis reported overall low risks for welfare, whereas enclosure analysis
      highlighted that the enclosure was suitable for allowing interactions without
      jeopardising animal welfare, mainly because it allowed animals to choose whether
      to interact or withdraw from interactions without decreasing the space available
      to them.

PMID- 30200195
TI  - Joint Source and Channel Rate Allocation over Noisy Channels in a Vehicle
      Tracking Multimedia Internet of Things System.
AB  - As an emerging type of Internet of Things (IoT), multimedia IoT (MIoT) has been
      widely used in the domains of healthcare, smart buildings/homes, transportation
      and surveillance. In the mobile surveillance system for vehicle tracking,
      multiple mobile camera nodes capture and upload videos to a cloud server to track
      the target. Due to the random distribution and mobility of camera nodes, wireless
      networks are chosen for video transmission. However, the tracking precision can
      be decreased because of degradation of video quality caused by limited wireless
      transmission resources and transmission errors. In this paper, we propose a joint
      source and channel rate allocation scheme to optimize the performance of vehicle
      tracking in cloud servers. The proposed scheme considers the video content
      features that impact tracking precision for optimal rate allocation. To improve
      the reliability of data transmission and the real-time video communication,
      forward error correction is adopted in the application layer. Extensive
      experiments are conducted on videos from the Object Tracking Benchmark using the
      H.264/AVC standard and a kernelized correlation filter tracking scheme. The
      results show that the proposed scheme can allocate rates efficiently and provide
      high quality tracking service under the total transmission rate constraints.

PMID- 30200197
TI  - Comparison of Fabrication Methods of Metal-Organic Framework Optical Thin Films.
AB  - Homogeneous metal-organic frameworks (MOFs)-based optical thin films have
      attracted increasing attention, since they can potentially be used as active
      components in optical/opt-electrical devices, and how to fabricate MOF thin films
      with high quality is the premise of practically using them. Herein, five
      fabrication methods of MOF films are systematically investigated and compared
      from the aspects of appearance, reflectivity, micro-morphology, surface
      roughness, and optical properties of the films. The famous robust Zr-based MOF,
      UiO-66 (UiO = University of Oslo) is chosen as a model, and the five methods are
      spin-coating, dip-coating, self-assembly, direct growth, and the stepwise layer
      by layer growth method. This study provides fundamental support for the
      application of MOFs in the optical field.

PMID- 30200196
TI  - Healthy Indoor Environments: The Need for a Holistic Approach.
AB  - Indoor environments have a large impact on health and well-being, so it is
      important to understand what makes them healthy and sustainable. There is
      substantial knowledge on individual factors and their effects, though
      understanding how factors interact and what role occupants play in these
      interactions (both causative and receptive) is lacking. We aimed to: (i) explore
      interactions between factors and potential risks if these are not considered from
      holistic perspective; and (ii) identify components needed to advance research on
      indoor environments. The paper is based on collaboration between researchers from
      disciplines covering technical, behavioural, and medical perspectives. Outcomes
      were identified through literature reviews, discussions and workshops with
      invited experts and representatives from various stakeholder groups. Four themes
      emerged and were discussed with an emphasis on occupant health: (a) the bio
      psycho-social aspects of health; (b) interaction between occupants, buildings and
      indoor environment; (c) climate change and its impact on indoor environment
      quality, thermal comfort and health; and (d) energy efficiency measures and
      indoor environment. To advance the relevant research, the indoor environment must
      be considered a dynamic and complex system with multiple interactions. This calls
      for a transdisciplinary and holistic approach and effective collaboration with
      various stakeholders.

PMID- 30200198
TI  - Unbiased Identification of Proteins Covalently Modified by Complex Mixtures of
      Peroxidized Lipids Using a Combination of Electrophoretic Mobility Band Shift
      with Mass Spectrometry.
AB  - Covalent modification of functionally important cell proteins by lipid oxidation
      products (LOPs) is a known mechanism initiating pathological consequences of
      oxidative stress. Identification of new proteins covalently modified by
      electrophilic lipids can be performed by a combination of chemical,
      immunological, and mass spectrometry-based methods, but requires prior knowledge
      either on the exact molecular structure of LOPs (e.g., 4-hydroxynonenal) or
      candidate protein targets. However, under the conditions of oxidative stress in
      vivo, a complex mixture of proteins (e.g., cytosolic proteome) reacts with a
      complex mixture of LOPs. Here we describe a method for detection of lipid
      modified proteins that does not require an a priori knowledge on the chemical
      structure of LOPs or identity of target proteins. The method is based on the
      change of electrophoretic mobility of lipid-modified proteins, which is induced
      by conformational changes and cross-linking with other proteins. Abnormally
      migrating proteins are detected by mass spectrometry-based protein peptide
      sequencing. We applied this method to study effects of oxidized palmitoyl
      arachidonoyl-phosphatidylcholine (OxPAPC) on endothelial cells. Several known,
      but also many new, OxPAPC-binding proteins were identified. We expect that this
      technically relatively simple method can be widely applied for label-free
      analysis of lipid-protein interactions in complex protein samples treated with
      different LOPs.

PMID- 30200199
TI  - Development of Model Predictive Controller for a Tail-Sitter VTOL UAV in Hover
      Flight.
AB  - This paper presents a model predictive controller (MPC) for position control of a
      vertical take-off and landing (VTOL) tail-sitter unmanned aerial vehicle (UAV) in
      hover flight. A 'cross' configuration quad-rotor tail-sitter UAV is designed with
      the capabilities for both hover and high efficiency level flight. The six-degree
      of-freedom (DOF) nonlinear dynamic model of the UAV is built based on aerodynamic
      data obtained from wind tunnel experiments. The model predictive position
      controller is then developed with the augmented linearized state-space model.
      Measured and unmeasured disturbance model are introduced into the modeling and
      optimization process to improve disturbance rejection ability. The MPC controller
      is first verified and tuned in the hardware-in-loop (HIL) simulation environment
      and then implemented in an on-board flight computer for real-time indoor
      experiments. The simulation and experimental results show that the proposed MPC
      position controller has good trajectory tracking performance and robust position
      holding capability under the conditions of prevailing and gusty winds.

PMID- 30200201
TI  - Schizophrenia and Sleep Disorders: An Introduction.
AB  - This editorial is an introduction to the special issue 'Schizophrenia and Sleep
      Disorders'.[...].

PMID- 30200200
TI  - Which School Community Agents Influence Adolescents' Motivational Outcomes and
      Physical Activity? Are More Autonomy-Supportive Relationships Necessarily Better?
AB  - The first aim of this work was to examine the independent influence of students'
      perceived autonomy support for leisure-time physical activity (LTPA), from
      different school community agents, on motivational outcomes in a LTPA context and
      objective PA levels. Using both a variable- and person-centered approach, the
      second aim was to examine how different combinations of autonomy-support were
      associated with students' motivational outcomes in a LTPA context and PA levels.
      A sample of 178 secondary students (M = 13.26 +/- 0.64) participated in the
      study. Autonomy support for LTPA from the PE teacher, mother, father, and peers
      were the only agents that significantly and positively predicted motivational
      outcomes in a LTPA context and PA levels. While the two- and three-way
      interactions of some of these four significant sources significantly increased
      the explained variance of some motivational outcomes, the plots revealed that the
      lowest values of motivational outcomes were associated with low values of
      perceived autonomy support. A cluster analysis revealed five profiles. The "high
      autonomy support" group reported the most optimal outcomes, whereas the "low
      autonomy support" group showed the opposite pattern. However, mixed autonomy
      support profiles did not differ in any of the outcomes. The adoption of a whole
      of-school approach seems decisive to empower adolescents to be active in and out
      of school.

PMID- 30200202
TI  - Difference DV_Distance Localization Algorithm Using Correction Coefficients of
      Unknown Nodes.
AB  - Node localization is an essential requirement in the increasing prevalence of
      wireless sensor networks applications. As the most commonly used localization
      algorithm, the DV_Distance algorithm is more sensitive to ranging error, and also
      has lower localization accuracy. Therefore, this paper proposes a novel
      difference DV_Distance localization algorithm using correction coefficients of
      unknown nodes. Taking account of the fact that correction coefficients of unknown
      nodes should be different, the proposed method has employed the correction model
      based on unknown nodes. Some correction coefficients for different direction
      anchor nodes can be indirectly calculated using the known difference of actual
      Euclidean distance and corresponding accumulated hop distance between anchor
      nodes, and then the weighting factors for the correction coefficients of
      different direction anchor nodes are also computed according to their actual
      contribution degree, so as to make sure that the corrected distances from unknown
      nodes to anchor nodes, modified by the final correction coefficient, are closer
      to the actual distances. At last, the positions of unknown nodes can be
      calculated using multilateral distance measurement. The simulation results
      demonstrate that the proposed approach is a localization algorithm with easier
      implementation, and it not only has better performance on localization accuracy
      than existing DV_Distance localization algorithm, but also improves the
      localization stability under the same experimental conditions.

PMID- 30200203
TI  - An Exploration of Parent-Youth Agreement on Functional Impairment in Adolescents
      Utilizing Outpatient Mental Health Services.
AB  - Parent-youth agreement on the youth's functional impairment may have important
      implications for mental health service utilization, assessment, therapy goal
      development, and treatment engagement for adolescents. The present study examines
      parent-youth agreement on their perceptions of youth functional impairment in a
      predominantly racial/ethnic minority sample of adolescents utilizing outpatient
      mental health services. Parent and youth functional impairment ratings were
      compared, and agreement was estimated in multiple ways. On average, parents
      indicated higher levels of youth functional impairment compared to youth in their
      overall scores, and when differences existed between parents and youth at the
      functioning domain and item level. Although there was similarity in the
      proportion of parents and youth who reported total impairment above the clinical
      cut-off, actual agreement between parent-youth pairs was only slight. There
      appeared to be substantial variation in agreement levels when identifying
      problems in functional impairment at the domain and item levels, and some areas
      of strong consensus were identified. These findings highlight the need to
      consider parent-youth agreement in perceptions of functional impairment and the
      complexities that may underlie this agreement.

PMID- 30200204
TI  - Selective Oxidation of Hydrogen Sulfide to Sulfur Using Vanadium Oxide Supported
      on Porous Clay Heterostructures (PCHs) Formed by Pillars Silica, Silica-Zirconia
      or Silica-Titania.
AB  - Vanadium oxide (V2O5) species has been supported on different porous clay
      heterostructures (with silica pillars, silica-zirconia with a molar ratio Si/Zr =
      5 and silica-titania with a molar ratio Si/Ti = 5) by wetness incipient method.
      All catalysts were characterized by X-ray diffraction (XRD), N2 adsorption
      desorption at -196  degrees C, NH3 thermoprogrammed desorption (NH3-TPD), Raman
      spectroscopy, diffuse reflectance UV-Vis and X-ray photoelectron spectroscopy
      (XPS). After that, the catalytic activity of the vanadium-based catalysts was
      evaluated in the selective oxidation of H2S to elemental sulfur. The catalytic
      data show that both the activity and the catalytic stability increase with the
      vanadium content, obtaining the highest conversion values and sulfur yield for
      the catalysts with vanadium content of 16 wt.%. The comparison among all supports
      reveals that the incorporation of TiO2 species in the pillars of the PCH improves
      the resistance to the deactivation, attaining as best results a H2S conversion of
      89% for SiTi-PCH-16V catalyst and elemental sulfur is the only compound detected
      by gas chromatography.

PMID- 30200205
TI  - Production, Quality, and Acceptance of Tempeh and White Bean Tempeh Burgers.
AB  - The food industry has been challenged to develop new healthy food products.
      Tempeh, originating in Indonesia and produced by fungal fermentation, would be an
      alternative healthy food for the Brazilian population. This study was designed to
      produce white bean (cv BRS Artico) tempeh burger, to determine and compare its
      nutritional and sensory properties with conventional soybean-based tempeh burger.
      The production and the analyses of proximal composition and microbiological
      contamination were determined in the tempeh, following reference methods. For the
      sensory analysis, a nine-point hedonic scale test was performed with 82 untrained
      evaluators, and at the end, a question of purchase intent was answered. The
      results indicated significant differences in the nutritional value of the
      tempehs, which is justified by the difference in the composition of the raw
      materials used. The samples did not present a risk of microbiological
      contamination for consumption. The white bean tempeh burgers showed similar
      appearance and crispy consistency, but received lower scores for flavor, compared
      to the soybean burgers, probably due to their residual beany flavor. The beany
      flavor could be minimized by increasing the cooking time of the beans. White bean
      tempeh can be a good alternative for healthy eating, and its manufacture could
      promote the production of new products made from beans, giving a new focus to the
      Brazilians' traditional food. It is still necessary to improve the techniques of
      production and test new ingredients for the preparation of tempeh burgers to
      obtain higher acceptability.

PMID- 30200206
TI  - The Potential Implications of Autonomous Vehicles in and around the Workplace.
AB  - The advent of autonomous vehicles is forecast to bring enormous changes to the
      workplace as positions primarily involving driving become progressively
      redundant. Little is known about public awareness of these impending changes and
      the potential impacts on society and individuals. This study involved a national
      survey of Australians and interviews with key stakeholders across multiple
      countries to identify major potential issues associated with vehicle automation,
      including in and around the workplace. Most survey respondents had concerns
      relating to job losses in driving occupations, while almost half anticipated
      increased employment in technology-related areas. Three primary themes were
      evident in the data from the stakeholder interviews: (1) the inevitability of the
      universal use of AVs and hence the immediate need for labour market planning, (2)
      associated potential effects on occupations that are not primarily structured
      around driving, and (3) the possibility of increased worker safety and enhanced
      commuting opportunities.

PMID- 30200207
TI  - Teachers' Strategies in Combating Diseases in Preschools' Environments.
AB  - Scholarship on child health indicates that the early years of life are vital for
      all aspects of health and development. In particular, a solid health foundation
      predicts good life outcomes; therefore, systematic strategies for combating
      diseases are needed to ensure optimal health of young children in early care
      environments. This study examined strategies used by 48 preschool teachers from
      10 pre-schools in the US Midwest in order to combat diseases. The following
      results emerged: Participants noted that children should not attend childcare if
      they are vomiting, have a fever or have diarrhea. They should be symptom-free for
      at least one day before returning to school. It is recommended that children be
      sent home if they have any disease deemed to have adverse effects on their health
      during the school day. Participants noted further that children must not share
      hats in their childcare environments to avoid transfer of head lice. Since no
      strategies were mentioned to help children cope with emotional distress and
      illness, it is recommended that teachers develop strategies that will address
      emotional childhood diseases in order to help all children.

PMID- 30200209
TI  - Mining Facebook Data of People with Rare Diseases: A Content-Based and Temporal
      Analysis.
AB  - This research characterized how Facebook deals with rare diseases. This
      characterization included a content-based and temporal analysis, and its purpose
      was to help users interested in rare diseases to maximize the engagement of their
      posts and to help rare diseases organizations to align their priorities with the
      interests expressed in social networks. This research used Netvizz to download
      Facebook data, word clouds in R for text mining, a log-likelihood measure in R to
      compare texts and TextBlob Python library for sentiment analysis. The Facebook
      analysis shows that posts with photos and positive comments have the highest
      engagement. We also observed that words related to diseases, attention,
      disability and services have a lot of presence in the decalogue of priorities
      (which serves for all associations to work on the same objectives and provides
      the lines of action to be followed by political decision makers) and little on
      Facebook, and words of gratitude are more present on Facebook than in the
      decalogue. Finally, the temporal analysis shows that there is a high variation
      between the polarity average and the hour of the day.

PMID- 30200208
TI  - Design, Synthesis and Biological Evaluation of Ligustrazine-Flavonoid Derivatives
      as Potential Anti-Tumor Agents.
AB  - In the clinic some anti-tumor drugs have shown damage to normal blood vessels,
      which could lead to vascular diseases. Therefore, it is necessary to evaluate the
      effects of anti-tumor drugs on normal blood vessels at the beginning of the drug
      design process. In this study, ligustrazine (TMP) and flavonoids were selected as
      raw materials. Sixteen novel TMP-flavonoid derivatives were designed and
      synthesized. Interestingly, compounds 14 and 16 were obtained by hydrolysis of a
      dihydroflavone to a chalcone under alkaline conditions. The cytotoxicity of the
      TMP-flavonoid derivatives was evaluated on five human tumor cell lines and one
      classical type of normal endothelial cell lines (HUVEC-12) by an MTT assay. Part
      of the derivatives showed better anti-tumor activities than the corresponding raw
      materials. Among them, compound 14 exhibited the closest activity to the positive
      control against the Bel-7402 cell line (IC50 = 10.74 +/- 1.12 MUM; DDP IC50 =
      6.73 +/- 0.37 MUM) and had no toxicity on HUVEC-12 (IC50 > 40 MUM). Subsequently,
      fluorescence staining and flow cytometry analysis indicated that compound 14
      could induce apoptosis of Bel-7402 cell lines. Moreover, the structure-activity
      relationships of these derivatives were briefly discussed.

PMID- 30200210
TI  - Transcriptome Analysis and In Situ Hybridization for FcaGHV1 in Feline Lymphoma.
AB  - Lymphoma is one of the most common malignancies in domestic cats. The
      lymphomagenic potential of Felis catus gammaherpesvirus 1 (FcaGHV1), a common
      infection in domestic cats, is unknown. In other species, including humans,
      cellular transformation by gammaherpesviruses is typically mediated by viral
      genes expressed during latency. We analysed tumour RNA, from diffuse large B-cell
      lymphomas (DLBCL) appearing in cats coinfected with FcaGHV1 and feline
      immunodeficiency virus (FIV) (n = 10), by high throughput transcriptome
      sequencing and reverse transcription PCR. A limited repertoire of FcaGHV
      transcripts was identified in five tumors, including homologs of oncogenic
      latency-associated transcripts, latency-associated nuclear antigen (LANA, ORF73)
      and vFLIP (F7), lytic genes (ORF50, ORF6, ORF59, F10), and an ORF unique to
      FcaGHV1, F20. In situ hybridization of FIV-associated DLBCLs (n = 9), post
      transplant lymphomas (n = 6) and high-grade B and T-cell intestinal lymphomas (n
      = 8) identified a single case in which FcaGHV1 nucleic acid was detectable. These
      results demonstrate that FcaGHV1 transcripts can be detected in some FIV
      associated lymphomas, but at low copy number, precluding assessment of a
      potential role for FcaGHV1 in lymphomagenesis. Future investigation of the
      FcaGHV1 transcriptome in clinical samples might employ viral enrichment and
      greater sequencing depth to enhance the retrieval of viral reads. Our results
      suggest prioritization of a subset of intestinal T-cell tumors, large granular
      lymphocyte lymphoma, for study.

PMID- 30200211
TI  - Anticoagulant and Antithrombotic Properties of Three Structurally Correlated Sea
      Urchin Sulfated Glycans and Their Low-Molecular-Weight Derivatives.
AB  - The anticoagulant and antithrombotic properties of three structurally correlated
      sea urchin-derived 3-linked sulfated alpha-glycans and their low molecular-weight
      derivatives were screened comparatively through various in vitro and in vivo
      methods. These methods include activated partial thromboplastin time, the
      inhibitory activity of antithrombin over thrombin and factor Xa, venous
      antithrombosis, the inhibition of platelet aggregation, the activation of factor
      XII, and bleeding. While the 2-sulfated fucan from Strongylocentrotus
      franciscanus was observed to be poorly active in most assays, the 4-sulfated
      fucan from Lytechinus variegatus, the 2-sulfated galactan from Echinometra
      lucunter and their derivatives showed multiple effects. All marine compounds
      showed no capacity to activate factor XII and similar low bleeding tendencies
      regardless of the dose concentrations used to achieve the highest antithrombotic
      effect observed. The 2-sulfated galactan showed the best combination of results.
      Our work improves the background about the structure-function relationship of the
      marine sulfated glycans in anticoagulation and antithrombosis. Besides confirming
      the negative effect of the 2-sulfated fucose and the positive effect of the 2
      sulfated galactose on anticoagulation in vitro, our results also demonstrate the
      importance of this set of structural requirements on antithrombosis in vivo, and
      further support the involvement of high-molecular weight and 4-sulfated fucose in
      both activities.

PMID- 30200212
TI  - The Negative Influence of Air Travel on Health and Performance in the National
      Basketball Association: A Narrative Review.
AB  - Air travel requirements are a concern for National Basketball Association (NBA)
      coaches, players, and owners, as sport-based research has demonstrated short-haul
      flights (<=6 h) increase injury risk and impede performance. However, examination
      of the impact of air travel on player health and performance specifically in the
      NBA is scarce. Therefore, we conducted a narrative review of literature examining
      the influence of air travel on health and performance in team sport athletes with
      suggestions for future research directions in the NBA. Prominent empirical
      findings and practical recommendations are highlighted pertaining to sleep,
      nutrition, recovery, and scheduling strategies to alleviate the negative effects
      of air travel on health and performance in NBA players.

PMID- 30200213
TI  - Effect of A Polyphenol-Rich Canarium album Extract on the Composition of the Gut
      Microbiota of Mice Fed a High-Fat Diet.
AB  - This study investigated the influence of Canarium album extract (CAext) on
      intestinal microbiota composition of mice fed a high-fat diet (HFD). Kun Ming
      (KM) mice were fed either a normal chow diet or a HFD for six weeks. At the
      seventh week, HFD-fed mice were gavaged daily with saline, or a different dose of
      CAext for four weeks, respectively. Then, the composition of the gut microbiota
      was analyzed by high-throughput sequencing technology. Analysis of fecal
      microbial populations, grouped by phyla, showed significant increases of
      Firmicutes and Verrucomicrobia, but a decrease of Bacteroidetes in all CAext-fed
      mice. Particularly, CAext gavage in a low dose or a medium dose caused a
      significant increase in the proportion of Akkermansia. These findings suggested
      that CAext can alter the gut microbiota composition of HFD-fed mice, and had a
      potential prebiotic effects on Akkermansia.

PMID- 30200214
TI  - Characterization of CYPs and UGTs Involved in Human Liver Microsomal Metabolism
      of Osthenol.
AB  - Osthenol is a prenylated coumarin isolated from the root of Angelica koreana and
      Angelica dahurica, and is an O-demethylated metabolite of osthole in vivo. Its
      various pharmacological effects have been reported previously. The metabolic
      pathway of osthenol was partially confirmed in rat osthole studies, and 11
      metabolic products were identified in rat urine. However, the metabolic pathway
      of osthenol in human liver microsomes (HLM) has not been reported. In this study,
      we elucidated the structure of generated metabolites using a high-resolution
      quadrupole-orbitrap mass spectrometer (HR-MS/MS) and characterized the major
      human cytochrome P450 (CYP) and uridine 5'-diphospho-glucuronosyltransferase
      (UGT) isozymes involved in osthenol metabolism in human liver microsomes (HLMs).
      We identified seven metabolites (M1-M7) in HLMs after incubation in the presence
      of nicotinamide adenine dinucleotide phosphate (NADPH) and uridine 5'
      diphosphoglucuronic acid (UDPGA). As a result, we demonstrated that osthenol is
      metabolized to five mono-hydroxyl metabolites (M1-M5) by CYP2D6, 1A2, and 3A4,
      respectively, a 7-O-glucuronide conjugate (M6) by UGT1A9, and a hydroxyl
      glucuronide (M7) from M5 by UGT1A3 in HLMs. We also found that glucuronidation is
      the dominant metabolic pathway of osthenol in HLMs.

PMID- 30200216
TI  - Application of an Improved Multipoint Optimal Minimum Entropy Deconvolution
      Adjusted for Gearbox Composite Fault Diagnosis.
AB  - The fault feature extraction of gearbox is difficult to achieve under complex
      working conditions, and this paper presents a hybrid fault diagnosis method for
      gearbox based on the combining product function (CPF) and multipoint optimal
      minimum entropy deconvolution adjusted (MOMEDA) methods. First, ensemble local
      mean decomposition (ELMD) is utilized to reduce the noise in original signal, and
      get a series of product functions (PFs), through the correlation coefficient
      method to remove false components and residual components. Then, multi-point
      kurtosis of the definition is achieved by calculating the multi-point kurtosis
      spectrum of each layer PF, and the fault feature period is extracted and the PFs
      without periodic impact are removed. After that, in order to maintain the
      integrity of the original signal, the PFs with the same period are recombined by
      the combined product function method. Finally, the different cycle interval is
      configured, reduce the noise through MOMEDA on the combined signal, to further
      extract the fault feature. The method is applied to the feature extraction of
      gear box composite fault to verify the feasibility of this method.

PMID- 30200217
TI  - High Hydrostatic Pressure as a Tool to Reduce Formation of Biogenic Amines in
      Artisanal Spanish Cheeses.
AB  - Two artisanal varieties of cheese made in Spain, one made of ewes' raw milk and
      the other of goats' raw milk were selected to evaluate the effect of a high
      hydrostatic pressure (HHP) treatment at 400 MPa during 10 min at 2  degrees C on
      the formation of biogenic amines (BA). These conditions were applied at the
      beginning of the ripening (before the 5th day; HHP1) and in the case of ewes'
      milk cheeses also after 15th days (HHP15). BA formation was greatly influenced by
      HHP treatments in both types of cheese. HHP1 treatments significantly reduced the
      amounts of BA after ripening, being tyramine and putrescine the most affected BA
      in goats' milk cheeses and tyramine and cadaverine in ewes' milk cheeses. The BA
      reduction in the HHP1 samples could be explained by the significant decrease in
      microbiological counts, especially in the LAB, enteroccocci and enterobacteria
      groups at the beginning of ripening. The proteolysis in these samples was also
      affected reducing the amount of free amino acids. Although proteolysis in ewes'
      milk cheeses HHP15 was similar than in control samples a reduction of BA was
      observed probably because the decrease caused on microbial counts.

PMID- 30200215
TI  - Are Colon and Rectal Cancer Two Different Tumor Entities? A Proposal to Abandon
      the Term Colorectal Cancer.
AB  - Colon cancer (CC) and rectal cancer (RC) are synonymously called colorectal
      cancer (CRC). Based on our experience in basic and clinical research as well as
      routine work in the field, the term CRC should be abandoned. We analyzed the
      available data from the literature and results from our multicenter Research
      Group Oncology of Gastrointestinal Tumors termed FOGT to confirm or reject this
      hypothesis. Anatomically, the risk of developing RC is four times higher than CC,
      while physical activity helps to prevent CC but not RC. Obvious differences exist
      in molecular carcinogenesis, pathology, surgical topography and procedures, and
      multimodal treatment. Therefore, we conclude that CC is not the same as RC. The
      term "CRC" should no longer be used as a single entity in basic and clinical
      research as well as other areas of classification.

PMID- 30200220
TI  - Mechanical Behavior of Liquid Nitrile Rubber-Modified Epoxy Resin under Static
      and Dynamic Loadings: Experimental and Constitutive Analysis.
AB  - Quasi-static and dynamic compression experiments were performed to study the
      influence of liquid nitrile rubber (LNBR) on the mechanical properties of epoxy
      resin. The quasi-static experiments were conducted by an electronic universal
      machine under strain rates of 0.0001/s and 0.001/s, while a Split Hopkinson
      Pressure Bar (SHPB) system was adopted to perform the dynamic tests for strain
      rates up to 5600/s. The standard Zhu-Wang-Tang (ZWT) nonlinear viscoelastic model
      was chosen to predict the elastic behavior of LNBR/epoxy composites under a wide
      range of strain rates. After some necessary derivation and data fitting, a set of
      model parameters for the tested materials were finally obtained. Meanwhile, the
      incremented form of the ZWT nonlinear viscoelastic model were deduced and
      implemented into the user material program of LS-DYNA. A simulation-test contrast
      had been performed to verify the validity and feasibility of the algorithm. The
      results showed that the viscoelastic behavior of epoxy resin can be effectively
      simulated.

PMID- 30200218
TI  - Gut Bacterial Communities of Dendroctonus valens and D. mexicanus (Curculionidae:
      Scolytinae): A Metagenomic Analysis across Different Geographical Locations in
      Mexico.
AB  - Dendroctonus bark beetles are a worldwide significant pest of conifers. This
      genus comprises 20 species found in North and Central America, and Eurasia.
      Several studies have documented the microbiota associated with these bark
      beetles, but little is known regarding how the gut bacterial communities change
      across host range distribution. We use pyrosequencing to characterize the gut
      bacterial communities associated with six populations of Dendroctonus valens and
      D. mexicanus each across Mexico, determine the core bacteriome of both insects
      and infer the metabolic pathways of these communities with Phylogenetic
      Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) to
      evaluate whether these routes are conserved across geographical locations. Our
      results show that the beta-diversity with UniFrac unweighted varies among
      locations of both bark beetles mainly due to absence/presence of some rare taxa.
      No association is found between the pairwise phylogenetic distance of bacterial
      communities and geographic distance. A strict intraspecific core bacteriome is
      determined for each bark beetle species, but these cores are different in
      composition and abundance. However, both bark beetles share the interspecific
      core bacteriome recorded previously for the Dendroctonus genus consisting of
      Enterobacter, Pantoea, Providencia, Pseudomonas, Rahnella, and Serratia. The
      predictions of metabolic pathways are the same in the different localities,
      suggesting that they are conserved through the geographical locations.

PMID- 30200219
TI  - Role of Transglutaminase 2 in Migration of Tumor Cells and How Mouse Models Fit.
AB  - A search for the "magic bullet", a molecule, the targeting abilities of which
      could stop the migration of tumor cells, is currently underway, but remains in
      the early stages. There are still many unknowns regarding the cell migration. The
      main approach is the employment of mouse models, that are sources of valuable
      information, but still cannot answer all of the questions. One of the molecules
      of interest is Transglutaminase 2 (TG2). It is a well-described molecule involved
      in numerous pathways and elevated in metastatic tumors. The question remains
      whether mice and humans can give the same answer considering TG2.

PMID- 30200221
TI  - Preparation of Quasi-Three-Dimensional Porous Ag and Ag-NiO Nanofibrous Mats for
      SERS Application.
AB  - In this study, two new quasi-three-dimensional Surface Enhanced Raman Scattering
      (SERS) substrates, namely porous Ag and Ag-NiO nanofibrous mats, were prepared
      using a simple, electrospinning-calcination, two-step synthetic process.
      AgNO3/polyvinyl pyrrolidone (PVP) and AgNO3/Ni(NO3)2/PVP composites serving as
      precursors were electrospun to form corresponding precursory nanofibers. Porous
      Ag and Ag-NiO nanofibers were successfully obtained after a 3-h calcination at
      500  degrees C under air atmosphere, and analyzed using various material
      characterization techniques. Synthesized, quasi-three-dimensional porous Ag and
      Ag-NiO nanofibrous mats were applied as SERS substrates, to measure the model
      compound Rhodamine 6G (R6G), and investigate the corresponding signal
      enhancement. Furthermore, porous Ag and Ag-NiO nanofibrous mats were employed as
      SERS substrates for melamine and methyl parathion respectively. Sensitive
      detection of melamine and methyl parathion was achieved, indicating their
      feasibility as an active SERS sensing platform, and potential for food safety and
      environmental monitoring. All the results suggest that the electrospinning
      calcination, two-step method offers a new, low cost, high performance solution in
      the preparation of SERS substrates.

PMID- 30200222
TI  - Measuring Thiols in Single Cultivar South African Red Wines Using 4,4
      Dithiodipyridine (DTDP) Derivatization and Ultraperformance Convergence
      Chromatography-Tandem Mass Spectrometry.
AB  - Wine varietal thiols are important contributors to wine aroma. The chemical
      nature of thiols makes them difficult to measure due to low concentrations, high
      sensitivity to oxidation, and low ionization. Methods for the measurement of
      thiols usually consist of multiple steps of sample preparation followed by
      instrumental measurement. Studies have collected large datasets of thiols in
      white wine but not in red wine, due to the lack of availability of suitable
      methods. In this study, for the first time, convergence chromatography was used
      to measure thiols in red wine at ultratrace levels with improved sensitivity
      compared to previous methods. Performance parameters (selectivity, linearity,
      limits of detection, precision, accuracy) were tested to demonstrate the
      suitability of the method for the proposed application. Red wine thiols were
      measured in South African Pinotage, Shiraz, and Cabernet Sauvignon wines (n = 16
      each). Cultivar differentiation using the thiol profile was demonstrated.

PMID- 30200223
TI  - Effect of Different Cooking Methods on Polyphenols, Carotenoids and Antioxidant
      Activities of Selected Edible Leaves.
AB  - This study aimed to evaluate the effect of cooking (boiling, steaming, and
      frying) on polyphenols, flavonoids, carotenoids and antioxidant activity of six
      edible leaves. The total antioxidant capacity of the fresh and cooked leaves was
      determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging and
      singlet oxygen scavenging assays. The results revealed that frying caused a
      reduction in major bioactives and antioxidant activities in all leafy vegetables
      tested. However, steamed and boiled leaves of C. auriculata and C. asiatica have
      shown greater levels of polyphenols, flavonoids, and antioxidant capacity
      compared with fresh leaves. Polyphenol and flavonoid contents of boiled S.
      grandiflora and G. lactiferum were higher than that of their fresh form. Boiled
      and steamed O. zeylanica and S. grandiflora have shown higher carotenoids. Boiled
      and steamed leaves of P. edulis have shown higher antioxidant activity. The
      impact of cooking on the changes in bioactive concentrations and antioxidant
      capacities are dependent on the species and the method of cooking.

PMID- 30200224
TI  - Synthesis and Tribological Properties of Bio-Inspired Nacre-Like Composites.
AB  - Ceramic materials possessing the properties of high-strength and rigidity are
      widely used in industry. The shell nacre has a layered structure containing both
      macroscopic and microscopic levels and is equipped with superior qualities
      regarding hardness and strength. Therefore, the ceramic composites with a nacre
      like layered structure have the potential to be utilized as sliding bearings
      employed in the harsh conditions of wells. For the purpose of this paper, a
      porous Al2O3 ceramics skeleton with nanometer powder is prepared using the freeze
      casting method. Then the porous ceramic skeleton is filled with polymer
      polymethyl methacrylate (PMMA) through mass polymerization to produce a bionic
      Al2O3/PMMA composite with a lamellar structure. The properties of the prepared
      composite are determined by the analysis of micro-hardness, fracture toughness,
      friction coefficient, wear scar diameter, and the morphology of the worn surface.
      Consequent results indicate that elevation in the A12O3 powder, which acts as the
      initial solid phase content, prompts the ceramic slurry to exhibit an increase in
      viscosity and a gradual decrease in the pore size of the ceramic skeleton. The
      prepared layered Al2O3/PMMA composite possesses high fracture toughness, which
      closely resembles that of Al, is approximately four times that of the matrix of
      the Al2O3 ceramics and 16 times that of the PMMA. Three kinds of composites
      containing different solid phase content are subjected to testing involving
      lubrication by water-based drilling fluid to determine the friction coefficient
      of each. The results indicate that an increased load leads to a decreased
      friction coefficient while the impact of speed is not evident. Under dry
      conditions, the friction coefficient of three different composites tested,
      declines with elevated load and speed. With the use of water-based drilling fluid
      as lubrication, the wear scar diameter increases at higher speed, while dry
      conditions denote increased load. Abrasive wear is determined to be the principal
      form of erosion of layered Al2O3/PMMA composites.

PMID- 30200225
TI  - Toward the Synthesis and Improved Biopotential of an N-methylated Analog of a
      Proline-Rich Cyclic Tetrapeptide from Marine Bacteria.
AB  - An N-methylated analog of a marine bacteria-derived natural proline-rich
      tetracyclopeptide was synthesized by coupling the deprotected dipeptide fragments
      Boc-l-prolyl-l-N-methylleucine-OH and l-prolyl-l-N-methylphenylalanine-OMe. A
      coupling reaction was accomplished utilizing N,N'-Dicyclohexylcarbodidimde (DCC)
      and 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC.HCl) as coupling agents
      and Triethylamine (TEA) or N-methylmorpholine (NMM) as the base in the presence
      of the racemization suppressing agent. This was followed by the cyclization of
      the linear tetrapeptide fragment under alkaline conditions. The structure of the
      synthesized cyclooligopeptide was confirmed using quantitative elemental
      analysis, FTIR (Fourier-transform infrared spectroscopy), 1H NMR (Nuclear
      magnetic resonance spectroscopy), 13C NMR, and mass spectrometry. From the
      bioactivity results, it was clear that the newly synthesized proline-rich
      tetracyclopeptide exhibited better anthelmintic potential against Megascoplex
      konkanensis, Pontoscotex corethruses, and Eudrilus eugeniae at a concentration of
      2 mg/mL as well as improved antifungal activity against pathogenic dermatophytes
      Trichophyton mentagrophytes and Microsporum audouinii at a concentration of 6
      MUg/mL, as compared to non-methylated tetracyclopeptide. Moreover, N-methylated
      tetracyclopeptide displayed significant activity against pathogenic Candida
      albicans.

PMID- 30200226
TI  - Chemical Profiles and Simultaneous Quantification of Aurantii fructus by Use of
      HPLC-Q-TOF-MS Combined with GC-MS and HPLC Methods.
AB  - Aurantii fructus (AF) is a traditional Chinese medicine that has been used to
      improve gastrointestinal motility disorders for over a thousand years, but there
      is no exhaustive identification of the basic chemical components and
      comprehensive quality control of this herb. In this study, high-performance
      liquid chromatography coupled with quadrupole time of flight mass spectrometry
      (HPLC-Q-TOF-MS) and gas chromatography coupled mass spectrometry (GC-MS) were
      employed to identify the basic chemical compounds, and high-performance liquid
      chromatography (HPLC) was developed to determine the major biochemical markers
      from AF extract. There were 104 compounds belonging to eight structure types,
      including 13 amino acids or peptides, seven alkaloids, 18 flavanones, 14
      flavones, 15 polymethoxyflavonoids, six triterpenoids, nine coumarins, and 18
      volatile oils, as well as four other compounds that were systematically
      identified as the basic components from AF, and among them, 41 compounds were
      reported for the first time. Twelve bioactive ingredients were chosen as the
      benchmark markers to evaluate the quality of AF. The analysis was completed with
      a gradient elution at a flow rate of 0.7 mL/min within 55 min. This efficient
      method was validated showing good linearity, precision, stability, repeatability
      and recovery. Furthermore, the method was successfully applied to the
      simultaneous determination of 12 chemical markers in different samples of AF.
      This study could be applied to the identification of multiple bioactive
      substances and improve the quality control of AF.

PMID- 30200228
TI  - Microstructures, Mechanical Properties, and Corrosion Behavior of As-Cast Mg
      2.0Zn-0.5Zr-xGd (wt %) Biodegradable Alloys.
AB  - The Mg-Zn-Zr-Gd alloys belong to a group of biometallic alloys suitable for bone
      substitution. While biocompatibility arises from the harmlessness of the metals,
      the biocorrosion behavior and its origins remain elusive. Here, aiming for the
      tailored biodegradability, we prepared the Mg-2.0Zn-0.5Zr-xGd (wt %) alloys with
      different Gd percentages (x = 0, 1, 2, 3, 4, 5), and studied their
      microstructures and biocorrosion behavior. Results showed that adding a moderate
      amount of Gd into Mg-2.0Zn-0.5Zr alloys will refine and homogenize alpha-Mg
      grains, change the morphology and distribution of (Mg, Zn)3Gd, and lead to
      enhancement of mechanical properties and anticorrosive performance. At the
      optimized content of 3.0%, the fishbone-shaped network, ellipsoidal, and rod-like
      (Mg, Zn)3Gd phase turns up, along with the 14H-type long period stacking ordered
      (14H-LPSO) structures decorated with nanoscale rod-like (Mg, Zn)3Gd phases. The
      14H-LPSO structure only exists when x >= 3.0, and its content increases with the
      Gd content. The Mg-2.0Zn-0.5Zr-3.0Gd alloy possesses a better ultimate tensile
      strength of 204 +/- 3 MPa, yield strength of 155 +/- 3 MPa, and elongation of
      10.6 +/- 0.6%. Corrosion tests verified that the Mg-2.0Zn-0.5Zr-3.0Gd alloy
      possesses the best corrosion resistance and uniform corrosion mode. The
      microstructure impacts on the corrosion resistance were also studied.

PMID- 30200229
TI  - Biofilm Inhibitory Abscisic Acid Derivatives from the Plant-Associated
      Dothideomycete Fungus, Roussoella sp.
AB  - Roussoella species are well recorded from both monocotyledons and dicotyledons.
      As part of a research program to discover biologically active compounds from
      plant-associated Dothideomycetes in Thailand, the strain Roussoella sp. (MFLUCC
      17-2059), which represents an undescribed species, was isolated from Clematis
      subumbellata Kurz, fermented in yeast-malt medium and explored for its secondary
      metabolite production. Bioassay-guided fractionation of the crude extract yielded
      the new abscisic acid derivative, roussoellenic acid (1), along with
      pestabacillin B (2), a related congener, and the cyclodipeptide, cyclo(S-Pro-S
      Ile) (3). The structure of 1 was determined by 2D NMR spectroscopy and HR-ESIMS
      data analysis. Compounds 1 and 2 showed inhibitory activity on biofilm formation
      by Staphylococcus aureus. The biofilm formation of S. aureus was reduced to 34%
      at 16 ug/mL by roussoellenic acid (1), while pestabacillin B (2) only showed 36%
      inhibition at 256 ug/mL. In addition, compound 1 also had weak cytotoxic effects
      on L929 murine fibroblasts and human KB3-1 cancer cells.

PMID- 30200230
TI  - Charge Transport in Trap-Sensitized Infrared PbS Quantum-Dot-Based
      Photoconductors: Pros and Cons.
AB  - Control of quantum-dot (QD) surface chemistry offers a direct approach for the
      tuning of charge-carrier dynamics in photoconductors based on strongly coupled QD
      solids. We investigate the effects of altering the surface chemistry of PbS QDs
      in such QD solids via ligand exchange using 3-mercaptopropionic acid (MPA) and
      tetrabutylammonium iodide (TBAI). The roll-to-roll compatible doctor-blade
      technique was used for the fabrication of the QD solid films as the photoactive
      component in photoconductors and field-effect phototransistors. The ligand
      exchange of the QD solid film with MPA yields superior device performance with
      higher photosensitivity and detectivity, which is due to less dark current and
      lower noise level as compared to ligand exchange with TBAI. In both cases, the
      mechanism responsible for photoconductivity is related to trap sensitization of
      the QD solid, in which traps are responsible of high photoconductive gain values,
      but slow response times under very low incident optical power (<1 pW). At medium
      high incident optical powers (>100 pW), where traps are filled, both MPA- and
      TBAI-treated photodevices exhibit similar behavior, characterized by lower
      responsivity and faster response time, as limited by the mobility in the QD
      solid.

PMID- 30200227
TI  - ELF3, ELF5, EHF and SPDEF Transcription Factors in Tissue Homeostasis and Cancer.
AB  - The epithelium-specific ETS (ESE) transcription factors (ELF3, ELF5, EHF and
      SPDEF) are defined by their highly conserved ETS DNA binding domain and
      predominant epithelial-specific expression profile. ESE transcription factors
      maintain normal cell homeostasis and differentiation of a number of epithelial
      tissues, and their genetic alteration and deregulated expression has been linked
      to the progression of several epithelial cancers. Herein we review the normal
      function of the ESE transcription factors, the mechanisms by which they are
      dysregulated in cancers, and the current evidence for their role in cancer
      progression. Finally, we discuss potential therapeutic strategies for targeting
      or reactivating these factors as a novel means of cancer treatment.

PMID- 30200231
TI  - Frontiers of Additively Manufactured Metallic Materials.
AB  - Additive manufacturing (AM) (=3D printing) has emerged during the last few years
      as a powerful technological platform for fabrication of functional parts with
      unique complex geometries and superior functionalities that are next to
      impossible to achieve using conventional manufacturing techniques. Due to their
      importance in industrial applications and the maturity of the applicable AM
      techniques, metallic materials are at the forefront of the developments in AM. In
      this editorial, which has been written as a preamble to the special issue
      "Perspectives on Additively Manufactured Metallic Materials", I will highlight
      some of the frontiers of research on AM of metallic materials to help readers
      better understand the cutting edge of research in this area. Some of these topics
      are addressed in the articles appearing in this special issue, while others
      constitute worthy avenues for future research.

PMID- 30200232
TI  - Cross-Sectional Associations between Homoarginine, Intermediate Phenotypes, and
      Atrial Fibrillation in the Community-The Gutenberg Health Study.
AB  - Homoarginine has come into the focus of interest as a biomarker for
      cardiovascular disease. Atrial fibrillation (AF) causes a substantial increase in
      morbidity and mortality. Whether circulating homoarginine is associated with
      occurrence or persistence of AF and may serve as a new predictive biomarker
      remains unknown. We measured plasma levels of homoarginine in the population
      based Gutenberg health study (3761 patients included, of them 51.7% males), mean
      age 55.6 +/- 10.9 years-old. Associations between homoarginine and intermediate
      electrocardiographic and echocardiographic phenotypes and manifest AF were
      examined. Patients with AF (124 patients, of them 73.4% males) had a mean age
      64.8 +/- 8.6 years-old compared to a mean age of 55.3 +/- 10.9 in the population
      without AF (p-value < 0.001) and showed a less beneficial risk factor profile.
      The median homoarginine levels in individuals with and without AF were 1.9
      MUmol/L (interquartile range (IQR) 1.5-2.5) and 2.0 MUmol/L (IQR 1.5-2.5),
      respectively, p = 0.56. In multivariable-adjusted regression analyses
      homoarginine was not statistically significantly related to electrocardiographic
      variables. Among echocardiographic variables beta per standard deviation increase
      was -0.12 (95% confidence interval (CI) -0.23-(-0.02); p = 0.024) for left atrial
      area and -0.01 (95% CI -0.02-(-0.003); p = 0.013) for E/A ratio. The odds ratio
      between homoarginine and AF was 0.91 (95% CI 0.70-1.16; p = 0.45). In our large,
      population-based cross-sectional study, we did not find statistically significant
      correlations between lower homoarginine levels and occurrence or persistence of
      AF or most standard electrocardiographic phenotypes, but some moderate inverse
      associations with echocardiographic left atrial size and E/A. Homoarginine may
      not represent a strong biomarker to identify individuals at increased risk for
      AF. Further investigations will be needed to elucidate the role of homoarginine
      and cardiac function.

PMID- 30200233
TI  - PsCor413pm2, a Plasma Membrane-Localized, Cold-Regulated Protein from Phlox
      subulata, Confers Low Temperature Tolerance in Arabidopsis.
AB  - Low temperature stress adversely affects plant growth and development. Isolation
      and characterization of cold response genes from cold-tolerant plants help to
      understand the mechanism underlying low temperature tolerance. In this study,
      PsCor413pm2, a cold-regulated (COR) gene isolated from Phlox subulata, was
      transferred to Arabidopsis plants to investigate its function. Real-time
      quantitative PCR analysis revealed that PsCor413pm2 expression was induced by
      cold. Subcellular localization revealed that the PsCor413pm2-green fluorescent
      protein (GFP) fusion protein localized to the plasma membrane in tobacco and
      Arabidopsis plants. Furthermore, overexpression of PsCor413pm2 in Arabidopsis
      plants enhanced tolerance to low temperature stress. Transgenic Arabidopsis roots
      had more influx of Ca2+ after a cold shock than wild-type plants, as shown using
      non-invasive micro-test technology (NMT). Moreover, the transcription abundance
      of five COR and two C-repeat (CRT) binding factor (CBF) genes in transgenic
      Arabidopsis plants was higher than that in the wild-type plants under cold
      stress. Taken together, our results suggest that overexpression of PsCor413pm2
      enhances low temperature tolerance in Arabidopsis plants by affecting Ca2+ flux
      and the expression of stress-related COR and CBF genes.

PMID- 30200234
TI  - Virucidal and Synergistic Activity of Polyphenol-Rich Extracts of Seaweeds
      against Measles Virus.
AB  - Although preventable by vaccination, Measles still causes thousands of deaths
      among young children worldwide. The discovery of new antivirals is a good
      approach to control new outbreaks that cause such death. In this study, we tested
      the antiviral activity against Measles virus (MeV) of Polyphenol-rich extracts
      (PPs) coming from five seaweeds collected and cultivated in Mexico. An MTT assay
      was performed to determine cytotoxicity effect, and antiviral activity was
      measured by syncytia reduction assay and confirmed by qPCR. PPs from Ecklonia
      arborea (formerly Eisenia arborea, Phaeophyceae) and Solieria filiformis
      (Rhodophyta) showed the highest Selectivity Index (SI), >3750 and >576.9
      respectively. Both PPs extracts were selected to the subsequent experiments owing
      to their high efficacy and low cytotoxicity compared with ribavirin (SI of
      11.57). The combinational effect of PPs with sulphated polysaccharides (SPs) and
      ribavirin were calculated by using Compusyn software. Synergistic activity was
      observed by combining both PPs with low concentrations of Solieria filiformis SPs
      (0.01 ug/mL). The antiviral activity of the best combinations was confirmed by
      qPCR. Virucidal assay, time of addition, and viral penetration evaluations
      suggested that PPs act mainly by inactivating the viral particle. To our
      knowledge, this is the first report of the virucidal effect of Polyphenol-rich
      extracts of seaweeds.

PMID- 30200236
TI  - Cognitive Frailty Predicts Incident Dementia among Community-Dwelling Older
      People.
AB  - Cognitive frailty, defined as the presence of both frailty and cognitive
      impairment, is a risk factor for adverse events in older adults. However,
      prevalence rates of cognitive frailty are low (1.1-2.5%), so primary screening is
      unsuitable in community settings. The aim of the study was to examine whether a
      new definition of cognitive frailty, which was developed for primary screening,
      is useful to predict incident dementia in community-dwelling older adults. A
      total of 4570 older adults participated in the study (2326 women; average age,
      71.9 +/- 5.5 years). We defined physical frailty as the presence of >=1 of the
      following symptoms: slow walking speed and muscle weakness. Cognitive impairment
      was defined as >=1 symptom of cognitive impairment, indicated by an age- and
      education-adjusted score that was >=1.5 standard deviations below the reference
      threshold in word list memory, attention, executive function, and processing
      speed tests. Cognitive frailty was defined as comorbid physical frailty and
      cognitive impairment. The incidence of dementia was determined using data
      collected by the Japanese Health Insurance System over 36 months. The prevalence
      rates of physical frailty, cognitive impairment, and cognitive frailty were
      17.5%, 15.3%, and 9.8%, respectively. Cognitive impairment (hazard ratio [HR]:
      2.06, 95% confidence interval [95% CI]: 1.41-3.02) and cognitive frailty (HR:
      3.43, 95% CI: 2.37-4.97) were found to be significant risk factors for dementia.
      However, the association between dementia and physical frailty was not
      significant (HR: 1.13, 95% CI: 0.76-1.69). Individuals with comorbid physical
      frailty and cognitive impairment could have a higher risk of dementia than
      healthy older adults or older adults with either physical frailty or cognitive
      impairment alone.

PMID- 30200235
TI  - Cardiotonic Steroids and the Sodium Trade Balance: New Insights into Trade-Off
      Mechanisms Mediated by the Na+/K+-ATPase.
AB  - In 1972 Neal Bricker presented the "trade-off" hypothesis in which he detailed
      the role of physiological adaptation processes in mediating some of the
      pathophysiology associated with declines in renal function. In the late 1990's
      Xie and Askari published seminal studies indicating that the Na+/K+-ATPase (NKA)
      was not only an ion pump, but also a signal transducer that interacts with
      several signaling partners. Since this discovery, numerous studies from multiple
      laboratories have shown that the NKA is a central player in mediating some of
      these long-term "trade-offs" of the physiological adaptation processes which
      Bricker originally proposed in the 1970's. In fact, NKA ligands such as
      cardiotonic steroids (CTS), have been shown to signal through NKA, and
      consequently been implicated in mediating both adaptive and maladaptive responses
      to volume overload such as fibrosis and oxidative stress. In this review we will
      emphasize the role the NKA plays in this "trade-off" with respect to CTS
      signaling and its implication in inflammation and fibrosis in target organs
      including the heart, kidney, and vasculature. As inflammation and fibrosis
      exhibit key roles in the pathogenesis of a number of clinical disorders such as
      chronic kidney disease, heart failure, atherosclerosis, obesity, preeclampsia,
      and aging, this review will also highlight the role of newly discovered NKA
      signaling partners in mediating some of these conditions.

PMID- 30200238
TI  - Kinesin-2 Controls the Motility of RAB5 Endosomes and Their Association with the
      Spindle in Mitosis.
AB  - RAB5 is a small GTPase that belongs to the wide family of Rab proteins and
      localizes on early endosomes. In its active GTP-bound form, RAB5 recruits
      downstream effectors that, in turn, are responsible for distinct aspects of early
      endosome function, including their movement along microtubules. We previously
      reported that, at the onset of mitosis, RAB5positive vesicles cluster around the
      spindle poles and, during metaphase, move along spindle microtubules. RNAi
      mediated depletion of the three RAB5 isoforms delays nuclear envelope breakdown
      at prophase and severely affects chromosome alignment and segregation. Here we
      show that depletion of the Kinesin-2 motor complex impairs long-range movement of
      RAB5 endosomes in interphase cells and prevents localization of these vesicles at
      the spindle during metaphase. Similarly to the effect caused by RAB5 depletion,
      functional ablation of Kinesin-2 delays nuclear envelope breakdown resulting in
      prolonged prophase. Altogether these findings suggest that endosomal transport at
      the onset of mitosis is required to control timing of nuclear envelope breakdown.

PMID- 30200239
TI  - Anti-Obesity Effects of Collagen Peptide Derived from Skate (Raja kenojei) Skin
      Through Regulation of Lipid Metabolism.
AB  - This study investigated the anti-obesity effects of collagen peptide derived from
      skate skin on lipid metabolism in high-fat diet (HFD)-fed mice. All C57BL6/J male
      mice were fed a HFD with 60% kcal fat except for mice in the normal group which
      were fed a chow diet. The collagen-fed groups received collagen peptide (1050 Da)
      orally (100, 200, or 300 mg/kg body weight per day) by gavage, whereas the normal
      and control groups were given water (n = 9 per group). The body weight gain and
      visceral adipose tissue weight were lower in the collagen-fed groups than in the
      control group (p < 0.05). Plasma and hepatic lipid levels were significantly
      reduced by downregulating the hepatic protein expression levels for fatty acid
      synthesis (sterol regulatory element binding protein-1 (SREBP-1), fatty acid
      synthase (FAS), and acetyl-CoA carboxylase (ACC)) and cholesterol synthesis
      (SREBP-2 and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR)) and upregulating
      those for beta-oxidation (peroxisome proliferator-activated receptor alpha (PPAR
      alpha) and carnitine palmitoyltransferase 1 (CPT1)) and synthesis of bile acid
      (cytochrome P450 family 7 subfamily A member 1 (CYP7A1)) (p < 0.05). In the
      collagen-fed groups, the hepatic protein expression level of phosphorylated 5'
      adenosine monophosphate-activated protein kinase (p-AMPK) and plasma adiponectin
      levels were higher, and the leptin level was lower (p < 0.05). Histological
      analysis revealed that collagen treatment suppressed hepatic lipid accumulation
      and reduced the lipid droplet size in the adipose tissue. These effects were
      increased in a dose-dependent manner. The findings indicated that skate collagen
      peptide has anti-obesity effects through suppression of fat accumulation and
      regulation of lipid metabolism.

PMID- 30200237
TI  - BK Polyomavirus MicroRNA Levels in Exosomes Are Modulated by Non-Coding Control
      Region Activity and Down-Regulate Viral Replication When Delivered to Non
      Infected Cells Prior to Infection.
AB  - In immunosuppressed patients, BKPyV-variants emerge carrying rearranged non
      coding control-regions (rr-NCCRs) that increase early viral gene region (EVGR)
      expression and replication capacity. BKPyV also encodes microRNAs, which have
      been reported to downregulate EVGR-encoded large T-antigen transcripts, to
      decrease viral replication in infected cells and to be secreted in exosomes. To
      investigate the interplay of NCCR and microRNAs, we compared archetype- and rr
      NCCR-BKPyV infection in cell culture. We found that laboratory and clinical rr
      NCCR-BKPyV-strains show higher replication rates but significantly lower microRNA
      levels than archetype virus intracellularly and in exosomes. To investigate
      whether rr-NCCR or increased EVGR activity modulated microRNA levels, we examined
      the (sp1-4)NCCR-BKPyV, which has an archetype NCCR-architecture but shows
      increased EVGR expression due to point mutations inactivating one Sp1 binding
      site. We found that microRNA levels following (sp1-4)NCCR-BKPyV infection were as
      low as in rr-NCCR-variants. Thus, NCCR rearrangements are not required for lower
      miRNA levels. Accordingly, Sp1 siRNA knock-down decreased microRNA levels in
      archetype BKPyV infection but had no effect on (sp1-4)- or rr-NCCR-BKPyV.
      However, rr-NCCR-BKPyV replication was downregulated by exosome preparations
      carrying BKPyV-microRNA prior to infection. To explore the potential relevance in
      humans, urine samples from 12 natalizumab-treated multiple sclerosis patients
      were analysed. In 7 patients, rr-NCCR-BKPyV were detected showing high urine
      BKPyV loads but low microRNAs levels, whereas the opposite was seen in 5 patients
      with archetype BKPyV. We discuss the results in a dynamic model of BKPyV
      replication according to NCCR activity and exosome regulation, which integrates
      immune selection pressure, spread to new host cells and rr-NCCR emergence.

PMID- 30200240
TI  - Energy Transfer from Photosystem I to Thermally Reduced Graphene Oxide.
AB  - The energy transfer from photosynthetic complex photosystem I to thermally
      reduced graphene oxide was studied using fluorescence microscopy and
      spectroscopy, and compared against the structure in which monolayer epitaxial
      graphene was used as the energy acceptor. We find that the properties of reduced
      graphene oxide (rGO) as an energy acceptor is qualitatively similar to that of
      epitaxial graphene. Fluorescence quenching, which in addition to shortening of
      fluorescence decay, is a signature of energy transfer varies across rGO
      substrates and correlates with the transmission pattern. We conclude that the
      efficiency of the energy transfer depends on the number of rGO layers in the
      flakes and decreases with this number. Furthermore, careful analysis of
      fluorescence imaging data confirms that the energy transfer efficiency dependence
      on the excitation wavelength, also varies with the number of rGO flakes.

PMID- 30200241
TI  - Brillouin Dynamic Gratings-A Practical Form of Brillouin Enhanced Four Wave
      Mixing in Waveguides: The First Decade and Beyond.
AB  - Brillouin-Enhanced Four-Wave-Mixing techniques, which couple four optical beams
      through Brillouin nonlinearity, have gained popularity in the 1980's largely
      owing to their phase conjugation properties. Experiments were mainly conducted in
      liquid cells. The interest in Brillouin-Enhanced Four-Wave-Mixing has reawakened
      in the 2000's, following the quest for dynamically reconfigurable gratings in
      optical fibers. Termed Brillouin Dynamic Grating this time around, it is, in
      fact, an acoustic wave, optically generated by stimulated Brillouin scattering
      process between two pump waves. The acoustic wave either carries the coherent
      information encoded by the pump beams, or in the case of sensing applications,
      its properties are determined by the environmental parameters. This information,
      in turn, is imparted to the third phase-matched optical probe wave through the
      elasto-optic effect. Over the last decade, this mechanism allowed for the
      realization of many all-optical signal processing functions and has proven
      instrumental in distributed sensing applications. This paper describes the
      basics, as well as the state of the art, of BDG-based applications in optical
      fibers. It also surveys the efforts being done to carry over these concepts to
      the photonic chip level.

PMID- 30200243
TI  - miRNA-130a Significantly Improves Accuracy of SGA Nutritional Assessment Tool in
      Prediction of Malnutrition and Cachexia in Radiotherapy-Treated Head and Neck
      Cancer Patients.
AB  - BACKGROUND: Investigation of novel cachexia-related markers is one of the major
      challenges in contemporary oncology. Among studied markers, the miRNA seems to be
      promising due to its possibility to regulate genes responsible for induction of
      inflammatory response, muscle atrophy and fat tissue wasting. The aim of the
      study was to investigate the role of blood-circulating miRNA-130a in prediction
      of cancer cachexia in 70 head and neck cancer patients (HNC) subjected to
      radiotherapy. Moreover, diagnostic accuracy of SGA (Subjective Global Assessment)
      scoring and miRNA-130a level was evaluated in various cachexia models. RESULTS:
      miRNA-130a level negatively correlated with plasma TNF-alpha concentration (r = 
      0.560; p < 0.001). Patients with low miRNA expression had over 3-fold higher risk
      of body mass index (BMI) decrease below 18.5 after the termination of therapy;
      over 6-fold higher risk of losing over 5% of body weight and higher risk of >10%
      weight reduction odds ratio (OR) = 14.18 compared to other cases. ROC analysis
      performed for miRNA-130a allowed to distinguish cachectic patients (body weight
      loss >5%) from moderately or mildly malnourished ones with optimal sensitivity of
      79.4% and specificity of 80.8% area under the curve (AUC) = 0.865). miRNA
      significantly improved nutritional assessment conducted using SGA, achieving the
      following values: sensitivity 88.6%, specificity 94.3%, positive predictive value
      (PPV) 93.9%, negative predictive value (NPV).89.2%. CONCLUSION: miRNA-130a
      demonstrates potential clinical utility in prediction of cachexia prior to the
      therapy in HNC patients. Simultaneous use of both tools-SGA and miRNA
      significantly improved the accuracy in the diagnosis of cachexia.

PMID- 30200245
TI  - Processing Impact on Performance of Solid Dispersions.
AB  - The development of a weakly basic compound is often challenging due to changes in
      pH that the drug experiences throughout the gastrointestinal tract. As the drug
      transitions from the low pH of the stomach to the higher pH of the small
      intestine, drug solubility decreases. A stomach with a higher pH, caused by food
      or achlorhydric conditions brought about by certain medications, decreases even
      the initial solubility. This decreased drug solubility is reflected in lower in
      vivo exposures. In many cases, a solubility-enabling approach is needed to
      counteract the effect of gastrointestinal pH changes. Solid dispersions of
      amorphous drug in a polymer matrix have been demonstrated to be an effective tool
      to enhance bioavailability, with the potential to mitigate the food and
      achlorhydric effects frequently observed with conventional formulations. Because
      solid dispersions are in a metastable state, they are particularly sensitive to
      processing routes that may control particle attributes, stability, drug release
      profile, and bioperformance. A better understanding of the impacts of processing
      routes on the solid dispersion properties will not only enhance our ability to
      control the product properties, but also lower development risks. In this study,
      a weakly basic compound with greatly reduced solubility in higher pHs was
      incorporated into a solid dispersion via both spray drying and hot melt
      extrusion. The properties of the solid dispersion via these two processing routes
      were compared, and the impact on dissolution behavior and in vivo performance of
      the dispersions was investigated.

PMID- 30200244
TI  - The Targeted Pesticides as Acetylcholinesterase Inhibitors: Comprehensive Cross
      Organism Molecular Modelling Studies Performed to Anticipate the Pharmacology of
      Harmfulness to Humans In Vitro.
AB  - Commercially available pesticides were examined as Mus musculus and Homo sapiens
      acetylcholinesterase (mAChE and hAChE) inhibitors by means of ligand-based (LB)
      and structure-based (SB) in silico approaches. Initially, the crystal structures
      of simazine, monocrotophos, dimethoate, and acetamiprid were reproduced using
      various force fields. Subsequently, LB alignment rules were assessed and applied
      to determine the inter synaptic conformations of atrazine, propazine, carbofuran,
      carbaryl, tebufenozide, imidacloprid, diuron, monuron, and linuron. Afterwards,
      molecular docking and dynamics SB studies were performed on either mAChE or
      hAChE, to predict the listed pesticides' binding modes. Calculated energies of
      global minima (Eglob_min) and free energies of binding (?Gbinding) were
      correlated with the pesticides' acute toxicities (i.e., the LD50 values) against
      mice, as well to generate the model that could predict the LD50s against humans.
      Although for most of the pesticides the low Eglob_min correlates with the high
      acute toxicity, it is the ?Gbinding that conditions the LD50 values for all the
      evaluated pesticides. Derived pLD50 = f(?Gbinding) mAChE model may predict the
      pLD50 against hAChE, too. The hAChE inhibition by atrazine, propazine, and
      simazine (the most toxic pesticides) was elucidated by SB quantum mechanics (QM)
      DFT mechanistic and concentration-dependent kinetic studies, enriching the
      knowledge for design of less toxic pesticides.

PMID- 30200247
TI  - A Population-Based Conceptual Framework for Evaluating the Role of Healthcare
      Services in Place of Death.
AB  - BACKGROUND: There is a significant geographical disparity in place of death.
      Socio-demographic and disease-related variables only explain less than a quarter
      of the variation. Healthcare service factors may account for some (or much) of
      the remaining variation but their effects have never been systematically
      evaluated, partly due to the lack of a conceptual framework. This study aims to
      propose a population-based framework to guide the evaluation of the role of the
      healthcare service factors in place of death. METHODS: Review and synthesis of
      health service models that include the impact of a service component on either
      place of death/end of life care outcomes or service access/utilization. RESULTS:
      The framework conceptualizes the impact of healthcare services on the place of
      death as starting from the end of life care policies that in turn influence
      service commissioning and shape healthcare service characteristics, including
      service type, service capacity-facilities, service location, and workforce,
      through which service utilization and ultimately place of death are affected.
      Patient socio-demographics, disease-related variables, family and community
      support and social care also influence place of death, but they are not the focus
      of this framework and therefore are grouped as needs and other environmental
      factors. Information on service utilization, together with the place of death,
      creates loop feedback to inform policy and service commission. CONCLUSIONS: The
      framework provides guidance for analysis aiming to understand the role of
      healthcare services in place of death. It aids the interpretation of results in
      the light of existing knowledge and potentially identifies service factors that
      can be addressed to improve end of life care.

PMID- 30200246
TI  - The Maize WRKY Transcription Factor ZmWRKY40 Confers Drought Resistance in
      Transgenic Arabidopsis.
AB  - Abiotic stresses restrict the growth and yield of crops. Plants have developed a
      number of regulatory mechanisms to respond to these stresses. WRKY transcription
      factors (TFs) are plant-specific transcription factors that play essential roles
      in multiple plant processes, including abiotic stress response. At present,
      little information regarding drought-related WRKY genes in maize is available. In
      this study, we identified a WRKY transcription factor gene from maize, named
      ZmWRKY40. ZmWRKY40 is a member of WRKY group II, localized in the nucleus of
      mesophyll protoplasts. Several stress-related transcriptional regulatory elements
      existed in the promoter region of ZmWRKY40. ZmWRKY40 was induced by drought, high
      salinity, high temperature, and abscisic acid (ABA). ZmWRKY40 could rapidly
      respond to drought with peak levels (more than 10-fold) at 1 h after treatment.
      Overexpression of ZmWRKY40 improved drought tolerance in transgenic Arabidopsis
      by regulating stress-related genes, and the reactive oxygen species (ROS) content
      in transgenic lines was reduced by enhancing the activities of peroxide dismutase
      (POD) and catalase (CAT) under drought stress. According to the results, the
      present study may provide a candidate gene involved in the drought stress
      response and a theoretical basis to understand the mechanisms of ZmWRKY40 in
      response to abiotic stresses in maize.

PMID- 30200242
TI  - The Interplay between Circulating Tumor Cells and the Immune System: From Immune
      Escape to Cancer Immunotherapy.
AB  - Circulating tumor cells (CTCs) have aroused increasing interest not only in
      mechanistic studies of metastasis, but also for translational applications, such
      as patient monitoring, treatment choice, and treatment change due to tumor
      resistance. In this review, we will assess the state of the art about the study
      of the interactions between CTCs and the immune system. We intend to analyze the
      impact that the cells of the immune system have in limiting or promoting the
      metastatic capability of CTCs. To this purpose, we will examine studies that
      correlate CTCs, immune cells, and patient prognosis, and we will also discuss
      relevant animal models that have contributed to the understanding of the
      mechanisms of immune-mediated metastasis. We will then consider some studies in
      which CTCs seem to play a promising role in monitoring cancer patients during
      immunotherapy regimens. We believe that, from an accurate and profound knowledge
      of the interactions between CTCs and the immune system, new immunotherapeutic
      strategies against cancer might emerge in the future.

PMID- 30200248
TI  - A Novel Acoustic Filtering Sensor for Real-Time Tension Monitoring of Hoist Wire
      Ropes.
AB  - The real-time tension monitoring of wire ropes is a universal way to judge
      whether the hoist is overloaded in the special working environment of the coal
      mine. However, due to the strong drafts, unevenness of guide and flexible
      vibration of wire ropes, it is a challenge to monitor the tension with high
      accuracy. For this purpose, a new type of acoustic filtering sensor is designed
      in this study. To adapt to the violent vibration during the monitoring process, a
      structure with a cylindrical cavity and a narrow gap is designed in the sensor.
      The coupling between the internal fluid and sensor structure can greatly absorb
      the vibration energy. With the view of optimizing the filtering performance of
      the sensor, the influences on the filtering characteristics are presented and
      analyzed through employing different structural and acoustic parameters in
      simulations. Finally, acoustic filtering sensor prototypes based on optimized
      parameters are calibrated and tested in a real coal mine. The results have
      revealed that our acoustic filtering sensor can not only address the deficiencies
      of current pressure sensors in coal mining and achieve tension monitoring in real
      time, but is also able to diagnose and forecast the occurrence of tension
      imbalance accidents.

PMID- 30200249
TI  - Comorbidities and Complications in Idiopathic Pulmonary Fibrosis.
AB  - Though idiopathic pulmonary fibrosis (IPF) is characterized by single-organ
      involvement, many comorbid conditions occur within other organ systems. Patients
      with IPF may present during evolution different complications and comorbidities
      that influence the prognosis and modify the natural course of their disease. In
      this chapter, we highlight common comorbid conditions encountered in IPF, discuss
      disease-specific diagnostic modalities, and review the current treatment data for
      several key comorbidities. The diagnosis and treatment of these comorbidities is
      a challenge for the pulmonologist specialized in interstitial lung diseases
      (ILDs). We will focus on pulmonary emphysema, lung cancer, gastroesophageal
      reflux, pulmonary hypertension, obstructive sleep apnea (sleep disorders), and
      acute exacerbation of IPF.

PMID- 30200251
TI  - Bombyx mori Dihydroorotate Dehydrogenase: Knockdown Inhibits Cell Growth and
      Proliferation via Inducing Cell Cycle Arrest.
AB  - Dihydroorotate dehydrogenase (DHODH), in the de novo pyrimidine biosynthetic
      pathway, is the fourth enzyme of pyrimidine synthesis and is used to oxidize
      dihydroorotate and hence to orotat. We cloned and characterized here the dhod of
      silkworms, Bombyx mori. The full-length cDNA sequence of dhod is 1339 bp,
      including an open reading frame (ORF) of 1173 bp that encoded a 390 amino acid
      protein. And two domains were involved in the Dihydroorotate dehydrogenase amino
      acid sequence of silkworms, Bombyx mori (BmDHODH), namely a DHO_dh domain and a
      transmembrane domain in N-termina. The silkworm dhod is expressed throughout
      development and in nine tissues. Moreover, knockdown of the silkworm dhod gene
      reduced cell growth and proliferation through G2/M phase cell cycle arrest.
      Similarly, DHODH inhibitor (leflunomide) also reduced cell growth and
      proliferation, with a significant decrease of cyclin B and cdk2. DHODH is the
      fourth enzyme of pyrimidine synthesis, so we also found that leflunomide can
      inhibit, at least in part, the endomitotic DNA replication in silk glands cells.
      These findings demonstrate that downregulation of BmDHODH inhibits cell growth
      and proliferation in silkworm cells, and the endomitotic DNA replication in silk
      gland cells.

PMID- 30200250
TI  - A Systematic Review of Access to General Healthcare Services for People with
      Disabilities in Low and Middle Income Countries.
AB  - Background: A systematic review was undertaken to explore access to general
      healthcare services for people with disabilities in low and middle-income
      countries (LMICs). Methods: Six electronic databases were searched in February
      2017. Studies comparing access to general healthcare services by people with
      disabilities to those without disabilities from LMICs were included. Eligible
      measures of healthcare access included: utilisation, coverage, adherence,
      expenditure, and quality. Studies measuring disability using self-reported or
      clinical assessments were eligible. Title, abstract and full-text screening and
      data extraction was undertaken by the two authors. Results: Searches returned
      13,048 studies, of which 50 studies were eligible. Studies were predominantly
      conducted in sub-Saharan Africa (30%), Latin America (24%), and East Asia/Pacific
      (12%). 74% of studies used cross-sectional designs and the remaining used case
      control designs. There was evidence that utilisation of healthcare services was
      higher for people with disabilities, and healthcare expenditure was higher. There
      were less consistent differences between people with and without disabilities in
      other access measures. However, the wide variation in type and measurement of
      disability, and access outcomes, made comparisons across studies difficult.
      Conclusions: Developing common metrics for measuring disability and healthcare
      access will improve the availability of high quality, comparable data, so that
      healthcare access for people with disabilities can be monitored and improved.

PMID- 30200253
TI  - Energy-Efficient Power Allocation and Relay Selection Schemes for Relay-Assisted
      D2D Communications in 5G Wireless Networks.
AB  - Device-to-device (D2D) communications allows user equipment (UE) that are in
      close proximity to communicate with each other directly without using a base
      station. Relay-assisted D2D (RA-D2D) communications in 5G networks can be applied
      to support long-distance users and to improve energy efficiency (EE) of the
      networks. In this paper, we first establish a multi-relay system model where the
      D2D UEs can communicate with each other by reusing only one cellular uplink
      resource. Then, we apply an adaptive neuro-fuzzy inference system (ANFIS)
      architecture to select the best D2D relay to forward D2D source information to
      the expected D2D destination. Efficient power allocation (PA) in the D2D source
      and the D2D relay are critical problems for operating such networks, since the
      data rate of the cellular uplink and the maximum transmission power of the system
      need to be satisfied. As is known, 5G wireless networks also aim for low energy
      consumption to better implement the Internet of Things (IoT). Consequently, in
      this paper, we also formulate a problem to find the optimal solutions for PA of
      the D2D source and the D2D relay in terms of maximizing the EE of RA-D2D
      communications to support applications in the emerging IoT. To solve the PA
      problems of RA-D2D communications, a particle swarm optimization algorithm is
      employed to maximize the EE of the RA-D2D communications while satisfying the
      transmission power constraints of the D2D users, minimum data rate of cellular
      uplink, and minimum signal-to-interference-plus-noise-ratio requirements of the
      D2D users. Simulation results reveal that the proposed relay selection and PA
      methods significantly improve EE more than existing schemes.

PMID- 30200252
TI  - Reproductive Function in a Population of Young Faroese Men with Elevated Exposure
      to Polychlorinated Biphenyls (PCBs) and Perfluorinated Alkylate Substances
      (PFAS).
AB  - Semen quality may be adversely affected by exposure to environmental chemicals
      such as polychlorinated biphenyls (PCBs) and perfluorinated alkylate substances
      (PFASs) that are persistent and may act as endocrine disrupting compounds. The
      aim of this study was to explore whether PCBs or PFASs exposure were associated
      with abnormalities in semen quality or reproductive hormones in Faroese men. This
      population based cross-sectional study includes 263 Faroese men (24-26 years) who
      delivered a semen sample for assessment of sperm concentration, total sperm
      count, semen volume, morphology and motility. A blood sample was drawn and
      analyzed for reproductive hormones, PCBs and PFASs. Exposure to ?PCBs and
      perfluorooctane sulfonate (PFOS) was positively associated with sex hormone
      binding globulin (SHBG) and luteinizing hormone (LH). In addition, total
      testosterone (T) was positively associated with ?PCB. Both PCBs and PFOS appear
      to lead to increased SHBG, perhaps mediated via the liver. The higher total T
      associated with PCB may represent a compensatory adaption to elevated SHBG levels
      to maintain an unchanged free testosterone concentration. The positive
      association to LH for both PCBs and PFOS may indicate a direct adverse effect on
      the testosterone producing Leydig cells.

PMID- 30200255
TI  - Youth Physical Activity Patterns During School and Out-of-School Time.
AB  - This study describes age, sex, and season patterns in children's physical
      activity behaviors during discrete time periods, both in school and at home.
      Participants were 135 elementary, 67 middle, and 89 high-school students (128
      boys and 163 girls) involved in a larger school activity monitoring project. We
      examined time spent in moderate-to-vigorous physical activity (MVPA) at recess,
      physical education (PE), lunch, commuting to/from school, before-school, after
      school, evening, and weekend segments. Differences in MVPA by age, sex, and
      season were examined using a three-way analysis of variance and separately for
      each individual segment. Moderate-to-vigorous physical activity levels varied by
      context and were higher during recess (15.4 +/- 8.5 min) while at school, and on
      Saturdays (97.4 +/- 89.5 min) when youth were out-of-school. Elementary children
      were more active than their older counterparts only during lunch time, after
      school, and Sunday (p < 0.05). Boys were consistently more active than girls at
      all segments. Participants were only more active during non-winter than winter
      months during PE (p = 0.006), after-school (p < 0.001), and Sunday (p = 0.008)
      segments. These findings showed that activity levels in youth vary during the day
      and season. The segments reflect discrete time periods that can potentially be
      targeted and evaluated to promote physical activity in this population.

PMID- 30200256
TI  - Hyperspectral Data and Machine Learning for Estimating CDOM, Chlorophyll a,
      Diatoms, Green Algae and Turbidity.
AB  - Inland waters are of great importance for scientists as well as authorities since
      they are essential ecosystems and well known for their biodiversity. When
      monitoring their respective water quality, in situ measurements of water quality
      parameters are spatially limited, costly and time-consuming. In this paper, we
      propose a combination of hyperspectral data and machine learning methods to
      estimate and therefore to monitor different parameters for water quality. In
      contrast to commonly-applied techniques such as band ratios, this approach is
      data-driven and does not rely on any domain knowledge. We focus on CDOM,
      chlorophyll a and turbidity as well as the concentrations of the two algae types,
      diatoms and green algae. In order to investigate the potential of our proposal,
      we rely on measured data, which we sampled with three different sensors on the
      river Elbe in Germany from 24 June-12 July 2017. The measurement setup with two
      probe sensors and a hyperspectral sensor is described in detail. To estimate the
      five mentioned variables, we present an appropriate regression framework
      involving ten machine learning models and two preprocessing methods. This allows
      the regression performance of each model and variable to be evaluated. The best
      performing model for each variable results in a coefficient of determination R 2
      in the range of 89.9% to 94.6%. That clearly reveals the potential of the machine
      learning approaches with hyperspectral data. In further investigations, we focus
      on the generalization of the regression framework to prepare its application to
      different types of inland waters.

PMID- 30200257
TI  - Fully Bayesian Prediction Algorithms for Mobile Robotic Sensors under Uncertain
      Localization Using Gaussian Markov Random Fields.
AB  - In this paper, we present algorithms for predicting a spatio-temporal random
      field measured by mobile robotic sensors under uncertainties in localization and
      measurements. The spatio-temporal field of interest is modeled by a sum of a time
      varying mean function and a Gaussian Markov random field (GMRF) with unknown
      hyperparameters. We first derive the exact Bayesian solution to the problem of
      computing the predictive inference of the random field, taking into account
      observations, uncertain hyperparameters, measurement noise, and uncertain
      localization in a fully Bayesian point of view. We show that the exact solution
      for uncertain localization is not scalable as the number of observations
      increases. To cope with this exponentially increasing complexity and to be usable
      for mobile sensor networks with limited resources, we propose a scalable
      approximation with a controllable trade-off between approximation error and
      complexity to the exact solution. The effectiveness of the proposed algorithms is
      demonstrated by simulation and experimental results.

PMID- 30200259
TI  - Water Quality of Inflows to the Everglades National Park over Three Decades (1985
      2014) Analyzed by Multivariate Statistical Methods.
AB  - The Everglades, a vast subtropical wetland, dominates the landscape of south
      Florida and is widely recognized as an ecosystem of great ecological importance.
      Data from seven inflow sites to the Everglades National Park (ENP) were analyzed
      over three decades (1985-2014) for temporal trends by the STL (integrated
      seasonal-trend decomposition using LOESS) method. A cluster analysis (CA) and
      principal component analysis (PCA) were applied for the evaluation of spatial
      variation. The results indicate that the water quality change trend is closely
      associated with rainfall. Increasing rainfall results in increasing flow and
      thus, decreasing concentrations of nitrogen and phosphorus. Based on 10
      variables, the seven sampling stations were classified by CA into four distinct
      clusters: A, B, C, and D. The PCA analysis indicated that total nitrogen (TN) and
      total phosphorus (TP) are the main pollution factors, especially TN. The results
      suggest that non-point sources are the main pollution sources and best management
      practices (BMPs) effectively reduce organic nitrogen. However, TN and TP control
      is still the focus of future work in this area. Increasing the transfer water
      quantity can improve the water quality temporarily and planting submersed
      macrophytes can absorb nitrogen and phosphorus and increase the dissolved oxygen
      (DO) concentration in water, continuously improving the water quality.

PMID- 30200260
TI  - Mitigation Policy Acceptance Model: An Analysis of Individual Decision Making
      Process toward Residential Seismic Strengthening.
AB  - Mitigation policy is regarded as an effective strategy to achieve the purpose of
      building health resilience and reducing disaster risk with the current high
      frequency of environmental event occurrences. To enhance public acceptance of
      mitigation policy, the issue of decision-making behavior has been a concern of
      researchers and planners. In the past literature, qualitative measures employed
      to reveal the behavioral intention of hazard risk mitigation cause restricted
      outcomes due to the problem of sample representativeness and the fact that
      quantitative research is restricted to discuss the linear relationship between
      the two selected variables. The purpose of this article is to attempt to
      construct a Mitigation Policy Acceptance Model (MPAM) to analyze the behavioral
      intention of seismic risk mitigation strategies. Based on Dual Processing Theory,
      affective is conducted as the core variable for constructing two types of
      thinking processes, and the variables of risk perception, trust and
      responsibility are selected in MPAM from theories and past research. In this
      study, the mitigation policy of residential seismic strengthening, adapted in
      Yongkang District of Tainan, has been conducted as the case study. According to
      the results, the result of model fit test has confirmed the MPAM framework, and
      two thinking modes could be associated together when people face a risky decision
      making process. The variable of affective is the most effective factor to
      influence each variable, and a direct effect on intention is also shown in this
      model. The results could provide suggestions in communication risk strategies for
      the government.

PMID- 30200254
TI  - RNAs as Candidate Diagnostic and Prognostic Markers of Prostate Cancer-From Cell
      Line Models to Liquid Biopsies.
AB  - The treatment landscape of prostate cancer has evolved rapidly over the past five
      years. The explosion in treatment advances has been witnessed in parallel with
      significant progress in the field of molecular biomarkers. The advent of next
      generation sequencing has enabled the molecular profiling of the genomic and
      transcriptomic architecture of prostate and other cancers. Coupled with this, is
      a renewed interest in the role of non-coding RNA (ncRNA) in prostate cancer
      biology. ncRNA consists of several different classes including small non-coding
      RNA (sncRNA), long non-coding RNA (lncRNA), and circular RNA (circRNA). These
      families are under active investigation, given their essential roles in cancer
      initiation, development and progression. This review focuses on the evidence for
      the role of RNAs in prostate cancer, and their use as diagnostic and prognostic
      markers, and targets for treatment in this disease.

PMID- 30200258
TI  - S1 Subunit of Spike Protein from a Current Highly Virulent Porcine Epidemic
      Diarrhea Virus Is an Important Determinant of Virulence in Piglets.
AB  - Base on the sequence of S genes, which encode spike proteins, we previously
      identified three different types (North American, S INDEL, and S large-DEL types)
      of porcine epidemic diarrhea virus (PEDV) that have re-emerged in Japan since
      2013. Based on experimental infections with the North American and S large-DEL
      types, we also hypothesized that PEDV virulence may be linked to the S1 subunit
      of the S protein. To test this hypothesis, we have now assayed in gnotobiotic
      piglets various recombinant PEDVs generated by reverse genetics. Piglets
      inoculated with CV777 maintained in National Institute of Animal Health, along
      with piglets infected with a recombinant form of the same virus, developed
      subclinical to mild diarrhea. In contrast, severe watery diarrhea, dehydration,
      weight loss, astasia, and high mortality were observed in piglets inoculated with
      recombinant strains in which the S gene was partially or fully replaced with
      corresponding sequences from the highly virulent Japanese PEDV isolate OKN
      1/JPN/2013. Indeed, symptoms resembled those in piglets inoculated with the OKN
      1/JPN/2013, and were especially pronounced in younger piglets. Collectively, the
      data demonstrate that the S1 subunit of the S protein is an important determinant
      of PEDV virulence, and advance development of new vaccine candidate.

PMID- 30200261
TI  - o-Carboranylalkoxy-1,3,5-Triazine Derivatives: Synthesis, Characterization, X-ray
      Structural Studies, and Biological Activity.
AB  - Morpholine- and bis(2-methoxyethyl)amine-substituted 1,3,5-triazine derivatives
      containing an alkoxy-o-carborane in the 6-position of the triazine ring were
      successfully synthesized. The molecular structures of the methoxy- and ethoxy-o
      carboranyl-1,3,5-triazines were established by X-ray crystallography. In vitro
      studies showed that the methylene bridged morpholine- and bis(2
      methoxyethyl)amine-substituted o-carboranyl-1,3,5-triazines accumulated to high
      levels in B16 melanoma cells and exhibited higher cytotoxicity than p
      boronophenylalanine.

PMID- 30200262
TI  - Targeting Breast Cancer Stem Cells to Overcome Treatment Resistance.
AB  - Despite advances in breast cancer diagnosis and treatment, many patients still
      fail therapy, resulting in disease progression, recurrence, and reduced overall
      survival. Historically, much focus has been put on the intrinsic subtyping based
      in the presence (or absence) of classical immunohistochemistry (IHC) markers such
      as estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth
      factor receptor-related protein (HER2). However, it is widely understood that
      tumors are composed of heterogeneous populations of cells with a hierarchical
      organization driven by cancer stem cells (CSCs). In breast tumors, this small
      population of cells displaying stem cell properties is known as breast CSCs
      (BCSCs). This rare population exhibit a CD44+/CD24-/low phenotype with high ALDH
      activity (ALDH+), and possesses higher tolerability to chemotherapy, hormone
      therapy, and radiotherapy and is able to reproduce the bulk of the tumor after
      reduction of cell populations sensitive to first-line therapy leading to disease
      relapse. In this review, we present special attention to BCSCs with future
      directions in the establishment of a therapy targeting this population. Drugs
      targeting the main BCSCs signaling pathways undergoing clinical trials are also
      summarized.

PMID- 30200263
TI  - Organ-Specific Oxidative Events under Restrictive Versus Full Reperfusion
      Following Hemorrhagic Traumatic Shock in Rats.
AB  - : Background aim: Reperfusion after hemorrhagic traumatic shock (HTS) is often
      associated with complications that are partly ascribed to the formation of
      reactive oxygen species (ROS). The aim of our study was to compare the effects of
      restrictive reperfusion (RR) to rapid full reperfusion (FR) on ROS formation
      and/or oxidative events. MATERIALS AND METHODS: Anesthetized male rats were
      randomly subjected to HTS followed by FR (75 mL/kg/h) or RR (30 mL/kg/h for 40
      min, followed by 75 mL/kg/h) with Ringer's solution (n = 8/group). Compartment
      specific ROS formation was determined by infusion of ROS scavenger 1-hydroxy-3
      carboxy-2,2,5,5-tetramethyl-pyrrolidine hydrochloride (CP-H) during
      resuscitation, followed by electron paramagnetic resonance spectroscopy. Sham
      operated animals (n = 8) served as controls. The experiment was terminated 100
      min post-shock. RESULTS: Mean arterial pressure was significantly higher in the
      FR compared to the RR group during early reperfusion. Only RR animals, not FR
      animals, showed significantly higher ROS concentrations in erythrocytes (1951 +/-
      420 vs. 724 +/- 75 AU) and in liver (474 +/- 57 vs. 261 +/- 21 AU) compared to
      sham controls. This was accompanied by elevated alanine aminotransferase and
      creatinine levels in RR animals compared to both shams and FR animals, while
      lipid peroxidation products (thiobarbituric acid reactive substances) were
      significantly increased only in the kidney in the FR group (p < 0.05). RR animals
      showed significantly higher plasma peroxiredoxin-4 values when compared to the FR
      group (20 +/- 2 vs. 14 +/- 0.5 RLU). CONCLUSION: Restrictive reperfusion after
      HTS is associated with increased ROS formation in erythrocytes and liver compared
      to sham controls. Moreover, the restrictive reperfusion is associated with a more
      pronounced injury to the liver and kidney, which is likely mediated by other than
      lipid peroxidation process and/or oxidative stress reactions.

PMID- 30200264
TI  - Photochemical and Structural Studies on Cyclic Peptide Models.
AB  - Ultra-violet (UV) irradiation has a significant impact on the structure and
      function of proteins that is supposed to be in relationship with the tryptophan
      mediated photolysis of disulfide bonds. To investigate the correlation between
      the photoexcitation of Trp residues in polypeptides and the associated reduction
      of disulfide bridges, a series of small, cyclic oligopeptide models were analyzed
      in this work. Average distances between the aromatic side chains and the
      disulfide bridge were determined following molecular mechanics (MM) geometry
      optimizations. In this way, the possibility of cation-pi interactions was also
      investigated. Molecular mechanics calculations revealed that the shortest
      distance between the side chain of the Trp residues and the disulfide bridge is
      approximately 5 A in the cyclic pentapeptide models. Based on this, three
      tryptophan-containing cyclopeptide models were synthesized and analyzed by
      nuclear magnetic resonance (NMR) spectroscopy. Experimental data and detailed
      molecular dynamics (MD) simulations were in good agreement with MM geometry
      calculations. Selected model peptides were subjected to photolytic degradation to
      study the correlation of structural features and the photolytic cleavage of
      disulfide bonds in solution. Formation of free sulfhydryl groups upon
      illumination with near UV light was monitored by fluorescence spectroscopy after
      chemical derivatization with 7-diethylamino-3-(4-maleimidophenyl)-4
      methylcoumarin (CPM) and mass spectrometry. Liquid cromatography-mass
      spectrometry (LC-MS) measurements indicated the presence of multiple
      photooxidation products (e.g., dimers, multimers and other oxidated products),
      suggesting that besides the photolysis of disulfide bonds secondary photolytic
      processes take place.

PMID- 30200266
TI  - An Investigation into the Quality of Medicines in Yangon, Myanmar.
AB  - Many poor-quality medicines are supplied to patients mainly in developing
      countries. No systematic survey on counterfeit medicines has been conducted in
      Myanmar since 1999. The purpose of this study was to investigate the current
      situation of substandard or counterfeit medicines in Myanmar. Samples of oral
      medicines, cefuroxime axetil (CXM), donepezil hydrochloride (DN) and omeprazole
      (OM), and injections, ceftriaxone sodium (CTRX), and gentamicin sulfate (GM),
      were collected from pharmacies, hospitals, and wholesalers in Yangon, Myanmar in
      2014. Authenticity and quality were verified. There were 221 (94%) foreign
      medicines among 235 collected samples. Five samples of GM and 1 DN sample were
      not registered with the Food and Drug Administration, Myanmar. In quality
      analysis, 36 samples out of 177 (20.3%) did not pass quantity tests, 27 samples
      out of 176 (15.3%) did not pass content uniformity tests, and 23 out of 128
      samples (18.0%) did not pass dissolution tests. Three of the unregistered GM
      samples failed in both identification and microbial assay tests. Counterfeit GM
      is being sold in Yangon. Also, the quality of OM is a matter of concern. Poor
      quality medicines were frequently found among the products of a few
      manufacturers. Regular surveys to monitor counterfeit and substandard medicines
      in Myanmar are recommended.

PMID- 30200267
TI  - Development of Magnetically Active Scaffolds for Bone Regeneration.
AB  - This work reports on the synthesis, with the thermally induced phase separation
      (TIPS) technique, of poly (l-lactide) (PLLA) scaffolds containing Fe-doped
      hydroxyapatite (FeHA) particles for bone regeneration. Magnetization curves and X
      ray diffraction indicate two magnetic particle phases: FeHA and magnetite Fe3O4.
      Magnetic nanoparticles (MNPs) are approximately 30 +/- 5 nm in width and 125 +/-
      25 nm in length, and show typical ferromagnetic properties, including coercivity
      and rapid saturation magnetization. Scanning electron microscopy (SEM) images of
      the magnetic scaffolds reveal their complex morphology changes with MNP
      concentration. Similarly, at compositions of approximately 20% MNPs, the phase
      separation changes, passing from solid-liquid to liquid-liquid as revealed by the
      hill-like structures, with low peaks that give the walls in the SEM images a
      surface pattern of micro-ruggedness typical of nucleation mechanisms and growth.
      In vitro degradation experiments, carried out for more than 28 weeks,
      demonstrated that the MNPs delay the scaffold degradation process. Cytotoxicity
      is appreciated for FeHA content above 20%.

PMID- 30200268
TI  - A Sensor Based on a Spherical Parallel Mechanism for the Measurement of Fluid
      Velocity: Physical Modelling and Computational Analysis.
AB  - In this article, a new method was developed to measure the velocity of a fluid
      using a sensor, based on the use of a spherical parallel mechanism with three
      degrees-of-freedom (DOF). This sensor transforms the kinetic energy of the fluid
      into potential energy by deforming the parallel mechanism. This deformation is
      due to the impact of the fluid on a sphere attached to the platform of the
      parallel mechanism. Through the acquisition of data from a sensor using an
      inertial measurement unit (IMU) in the sphere, an algorithm calculates the
      velocity and direction of the fluid. In this article, a mathematical model of the
      mechanism and an algorithm for correctly measuring the velocity and direction of
      the fluid is developed; this algorithm is tested through a simulation in the
      Adams software, and the MATLAB software is used to execute the algorithm. The
      results show that the algorithm calculates the velocity and the direction of the
      fluid correctly, demonstrating the technical feasibility of the sensor.

PMID- 30200271
TI  - Experimental Characterization of the Thermal Conductivity and Microstructure of
      Opacifier-Fiber-Aerogel Composite.
AB  - Due to their high-porosity, nanoporous structure and pores, aerogel materials
      possess extremely low thermal conductivity and have broad potential in the
      thermal insulation field. Silica aerogel materials are widely used because of
      their low thermal conductivity and high temperature resistance. Pure silica
      aerogel is very fragile and nearly transparent to the infrared spectrum within 3
      8 MUm. Doping fibers and opacifiers can overcome these drawbacks. In this paper,
      the influences of opacifier type and content on the thermal conductivity of
      silica fiber mat-aerogel composite are experimentally studied using the transient
      plane source method. The thermal insulation performances are compared from 100 to
      750  degrees C at constant pressure in nitrogen atmosphere among pure fiber mat,
      fiber mat-aerogel, 20% SiC-fiber mat-aerogel, 30% ZrO2-fiber mat-aerogel and 20%
      SiC + 30% ZrO2-fiber mat-aerogel. Fiber mat-aerogel doped with 20% SiC has the
      lowest thermal conductivity, 0.0792 W/m.K at 750  degrees C, which proves that
      the proper type and moderate content of opacifier dominates the low thermal
      conductivity. The pore size distribution indicates that the volume fraction of
      the micropore and mesopore is also the key factor for reducing the thermal
      conductivity of porous materials.

PMID- 30200269
TI  - Resveratrol and Depression in Animal Models: A Systematic Review of the
      Biological Mechanisms.
AB  - Depression is currently treated by pharmacotherapies that can elicit debilitating
      side effects for patients. Novel treatment options with limited side effects are
      currently being researched. Resveratrol is a polyphenol and phytoalexin found in
      the skins of grapes, red wine, Japanese knotweed, and peanuts. It has been
      studied extensively for its antioxidant and anti-inflammatory properties.
      Resveratrol has also gained attention for its neuroprotective properties. The aim
      of the review was to examine the mechanisms by which resveratrol reduces
      depressive behaviors in animal models. In total, 22 studies met the established
      criteria for final review. Behavioral aspects of depression were investigated
      using validated measures such as the forced swimming test, tail suspension test,
      sucrose preference test, and open field test. While many physical measures were
      taken, three main biological mechanisms were explored: Regulation of the
      hypothalamic-pituitary-adrenal axis; decreased inflammation; and increased Brain
      Derived Neurotrophic Factor and neurogenesis. Based on these findings,
      resveratrol may be deemed an effective treatment for depression in animal models
      at doses between 10-80 mg/kg/day, although higher doses had the most significant
      effects. Future studies should examine the effects of resveratrol on depression
      in humans to determine the eligibility of resveratrol as a natural antidepressant
      with less severe side effects.

PMID- 30200270
TI  - Identification of Oxidative Stress in Red Blood Cells with Nanoscale Chemical
      Resolution by Infrared Nanospectroscopy.
AB  - During their lifespan, Red blood cells (RBC), due to their inability to self
      replicate, undergo an ageing degradation phenomenon. This pathway, both in vitro
      and in vivo, consists of a series of chemical and morphological modifications,
      which include deviation from the biconcave cellular shape, oxidative stress,
      membrane peroxidation, lipid content decrease and uncoupling of the membrane
      skeleton from the lipid bilayer. Here, we use the capabilities of atomic force
      microscopy based infrared nanospectroscopy (AFM-IR) to study and correlate, with
      nanoscale resolution, the morphological and chemical modifications that occur
      during the natural degradation of RBCs at the subcellular level. By using the tip
      of an AFM to detect the photothermal expansion of RBCs, it is possible to obtain
      nearly two orders of magnitude higher spatial resolution IR spectra, and
      absorbance images than can be obtained on diffraction-limited commercial Fourier
      transform Infrared (FT-IR) microscopes. Using this approach, we demonstrate that
      we can identify localized sites of oxidative stress and membrane peroxidation on
      individual RBC, before the occurrence of neat morphological changes in the
      cellular shape.

PMID- 30200272
TI  - Synthesis and Antioxidant Activity of Caffeic Acid Derivatives.
AB  - A series of caffeic acid derivatives were synthesized via a modified Wittig
      reaction which is a very important tool in organic chemistry for the construction
      of unsaturated carbon-carbon bonds. All reactions were performed in water medium
      at 90  degrees C. The aqueous Wittig reaction worked best when one unprotected
      hydroxyl group was present in the phenyl ring. The olefinations in the aqueous
      conditions were also conducted with good yields in the presence of two
      unprotected hydroxyl groups. When the number of the hydroxyl groups was increased
      to three, the reaction yields were worse, and the derivatives 12, 13, and 18 were
      obtained with 74%, 37%, and 70% yields, respectively. Nevertheless, the Wittig
      reaction using water as the essential medium is an elegant one-pot synthesis and
      a greener method, which can be a safe alternative for implementation in organic
      chemistry. The obtained compounds were tested for their antioxidant activity, and
      12, 13, and 18 showed the highest activities. Moreover, all synthesized compounds
      displayed no cytotoxicity, and can therefore be used in the pharmaceutical or
      cosmetic industry.

PMID- 30200273
TI  - Functional and Bioactive Properties of Food: The Challenges Ahead.

PMID- 30200265
TI  - Epigenetic Crosstalk between the Tumor Microenvironment and Ovarian Cancer Cells:
      A Therapeutic Road Less Traveled.
AB  - Metastatic dissemination of epithelial ovarian cancer (EOC) predominantly occurs
      through direct cell shedding from the primary tumor into the intra-abdominal
      cavity that is filled with malignant ascitic effusions. Facilitated by the fluid
      flow, cells distribute throughout the cavity, broadly seed and invade through
      peritoneal lining, and resume secondary tumor growth in abdominal and pelvic
      organs. At all steps of this unique metastatic process, cancer cells exist within
      a multidimensional tumor microenvironment consisting of intraperitoneally
      residing cancer-reprogramed fibroblasts, adipose, immune, mesenchymal stem,
      mesothelial, and vascular cells that exert miscellaneous bioactive molecules into
      malignant ascites and contribute to EOC progression and metastasis via distinct
      molecular mechanisms and epigenetic dysregulation. This review outlines basic
      epigenetic mechanisms, including DNA methylation, histone modifications,
      chromatin remodeling, and non-coding RNA regulators, and summarizes current
      knowledge on reciprocal interactions between each participant of the EOC cellular
      milieu and tumor cells in the context of aberrant epigenetic crosstalk. Promising
      research directions and potential therapeutic strategies that may encompass
      epigenetic tailoring as a component of complex EOC treatment are discussed.

PMID- 30200274
TI  - An Impedimetric Biosensor Based on Ionic Liquid-Modified Graphite Electrodes
      Developed for microRNA-34a Detection.
AB  - In the present work, an impedimetric nucleic acid biosensor has been designed for
      the purpose of detection of microRNA (miRNA). Ionic liquid (1-butyl-3
      methylimidazolium hexafluorophosphate (IL))-modified chemically activated pencil
      graphite electrodes (PGEs) were used for the sensitive and selective detection of
      miRNA-34a. After covalent activation of the PGE surface using covalent agents
      (CAs), the ionic liquid (IL) was immobilized onto the surface of the chemically
      activated PGE by passive adsorption. The electrochemical and microscopic
      characterization of the IL/CA/PGEs was performed by electrochemical impedance
      spectroscopy (EIS), cyclic voltammetry (CV) and scanning electron microscopy
      (SEM). DNA probe concentration, miRNA target concentration, and also the
      hybridization time and wet adsorption time were optimized by using the EIS
      technique. Then, the hybridization occurred between specific DNA probes and miRNA
      34a was immobilized onto the surface of the IL/CA/PGEs. The impedimetric
      detection of miRNA-DNA hybrid was performed by EIS. The detection limit (DL) was
      calculated in a linear concentration range of 2-10 ug/mL miRNA-34a target, and it
      was found to be 0.772 ug/mL (109 nM) in phosphate buffer solution (PBS) and 0.826
      ug/mL (117 nM) in diluted fetal bovine serum (FBS). The selectivity of
      impedimetric biosensor for miRNA-34a was also tested against to other non
      complementary miRNA sequences both in buffer media, or diluted FBS.

PMID- 30200275
TI  - Antiproliferative Activity of Non-Calcemic Vitamin D Analogs on Human Melanoma
      Lines in Relation to VDR and PDIA3 Receptors.
AB  - Vitamin D is a precursor for secosteroidal hormones, which demonstrate
      pleiotropic biological activities, including the regulation of growth and the
      differentiation of normal and malignant cells. Our previous studies have
      indicated that the inhibition of melanoma proliferation by a short side-chain,
      low calcemic analog of vitamin D-21(OH)pD is not fully dependent on the
      expression of vitamin D receptor (VDR). We have examined the effects of classic
      vitamin D metabolites, 1,25(OH)2D3 and 25(OH)D3, and two low calcemic vitamin D
      analogs, (21(OH)pD and calcipotriol), on proliferation, mRNA expression and
      vitamin D receptor (VDR) translocation in three human melanoma cell lines: WM98,
      A375 and SK-MEL-188b (subline b of SK-MEL-188, which lost responsiveness to
      1,25(OH)2D3 and became VDR-/-CYP27B1-/-). All tested compounds efficiently
      inhibited the proliferation of WM98 and A375 melanoma cells except SK-MEL-188b,
      in which only the short side-chain vitamin D analog-21(OH)pD was effective.
      Overall, 21(OH)pD was the most potent compound in all three melanoma cell lines
      in the study. The lack of responsiveness of SK-MEL-188b to 1,25(OH)2D3, 25(OH)D3
      and calcipotriol is explained by a lack of characteristic transcripts for the
      VDR, its splicing variants as well as for vitamin D-activating enzyme CYP27B1. On
      the other hand, the expression of VDR and its splicing variants and other vitamin
      D related genes (RXR, PDIA3, CYP3A4, CYP2R1, CYP27B1, CYP24A1 and CYP11A1) was
      detected in WM98 and A375 melanomas with the transcript levels being modulated by
      vitamin D analogs. The expression of VDR isoforms in WM98 cells was stimulated
      strongly by calcipotriol. The antiproliferative activities of 21(OH)pD appear not
      to require VDR translocation to the nucleus, which explains the high efficacy of
      this noncalcemic pregnacalciferol analog in SK-MEL-188b melanoma, that is, VDR-/
      . Therefore, we propose that 21(OH)pD is a good candidate for melanoma therapy,
      although the mechanism of its action remains to be defined.

PMID- 30200277
TI  - Impacts of Climate Change on Health and Wellbeing in South Africa.
AB  - Given its associated burden of disease, climate change in South Africa could be
      reframed as predominately a health issue, one necessitating an urgent health
      sector response. The growing impact of climate change has major implications for
      South Africa, especially for the numerous vulnerable groups in the country. We
      systematically reviewed the literature by searching PubMed and Web of Science. Of
      the 820 papers screened, 34 were identified that assessed the impacts of climate
      change on health in the country. Most papers covered effects of heat on health or
      on infectious diseases (20/34; 59%). We found that extreme weather events are the
      most noticeable effects to date, especially droughts in the Western Cape, but
      rises in vector-borne diseases are gaining prominence. Climate aberration is also
      linked in myriad ways with outbreaks of food and waterborne diseases, and
      possibly with the recent Listeria epidemic. The potential impacts of climate
      change on mental health may compound the multiple social stressors that already
      beset the populace. Climate change heightens the pre-existing vulnerabilities of
      women, fishing communities, rural subsistence farmers and those living in
      informal settlements. Further gender disparities, eco-migration and social
      disruptions may undermine the prevention-but also treatment-of HIV. Our findings
      suggest that focused research and effective use of surveillance data are required
      to monitor climate change's impacts; traditional strengths of the country's
      health sector. The health sector, hitherto a fringe player, should assume a
      greater leadership role in promoting policies that protect the public's health,
      address inequities and advance the country's commitments to climate change
      accords.

PMID- 30200276
TI  - Quantitative Infection Dynamics of Cafeteria Roenbergensis Virus.
AB  - The discovery of giant viruses in unicellular eukaryotic hosts has raised new
      questions on the nature of viral life. Although many steps in the infection cycle
      of giant viruses have been identified, the quantitative life history traits
      associated with giant virus infection remain unknown or poorly constrained. In
      this study, we provide the first estimates of quantitative infection traits of a
      giant virus by tracking the infection dynamics of the bacterivorous protist
      Cafeteria roenbergensis and its lytic virus CroV. Leveraging mathematical models
      of infection, we quantitatively estimate the adsorption rate, onset of DNA
      replication, latency time, and burst size from time-series data. Additionally, by
      modulating the initial ratio of viruses to hosts, we also provide evidence of a
      potential MOI-dependence on adsorption and burst size. Our work provides a
      baseline characterization of giant virus infection dynamics relevant to ongoing
      efforts to understand the ecological role of giant viruses.

PMID- 30200278
TI  - New Directions for SMA Therapy.
AB  - Spinal muscular atrophy (SMA) is a severe disorder of motor neurons and the most
      frequent genetic cause of mortality in childhood, due to respiratory
      complications. The disease occurs due to mutations in the survival motor neuron 1
      (SMN1) gene that leads to a reduction in the SMN protein, causing degeneration of
      lower motor neurons, muscle weakness and atrophy. Recently, the Food and Drug
      Administration (FDA) and the European Medical Agency (EMA) approved the antisense
      oligonucleotide nusinersen, the first disease-modifying treatment for SMA.
      Encouraging results from SMN1 gene therapy studies have raised hope for other
      therapeutic approaches that might arise in the coming years. However, nusinersen
      licensing has created ethical, medical, and financial implications that will need
      to be addressed. In this review, the history and challenges of the new SMA
      therapeutic strategies are highlighted.

PMID- 30200279
TI  - Genome-Wide Investigation of the Role of MicroRNAs in Desiccation Tolerance in
      the Resurrection Grass Tripogon loliiformis.
AB  - Drought causes approximately two-thirds of crop and yield loss worldwide. To
      sustain future generations, there is a need to develop robust crops with enhanced
      water use efficiency. Resurrection plants are naturally resilient and tolerate up
      to 95% water loss with the ability to revive upon watering. Stress is genetically
      encoded and resilient species may garner tolerance by tightly regulating the
      expression of stress-related genes. MicroRNAs (miRNAs) post-transcriptionally
      regulate development and other stress response processes in eukaryotes. However,
      their role in resurrection plant desiccation tolerance is poorly understood. In
      this study, small RNA sequencing and miRNA expression profiling was conducted
      using Tripogon loliiformis plants subjected to extreme water deficit conditions.
      Differentially expressed miRNA profiles, target mRNAs, and their regulatory
      processes were elucidated. Gene ontology enrichment analysis revealed that
      development, stress response, and regulation of programmed cell death biological
      processes; Oxidoreductase and hydrolyase molecular activities; and SPL, MYB, and
      WRKY transcription factors were targeted by miRNAs during dehydration stress,
      indicating the indispensable regulatory role of miRNAs in desiccation tolerance.
      This study provides insights into the molecular mechanisms of desiccation
      tolerance in the resurrection plant T. loliiformis. This information will be
      useful in devising strategies for crop improvement on enhanced drought tolerance
      and water use efficiency.

PMID- 30200281
TI  - The Effect of Repeated Botulinum Toxin A Therapy Combined with Intensive
      Rehabilitation on Lower Limb Spasticity in Post-Stroke Patients.
AB  - OBJECTIVES: This study is a retrospective investigation of the effects of
      repetitive botulinum toxin A therapy (BoNT-A) and intensive rehabilitation (IR)
      on lower limb spasticity in post-stroke patients. METHODS: Thirty-five post
      stroke patients was included in this study and received BoNT-A for the first
      time. A 12-day inpatient protocol was with 4 cycles of the treatment protocol.
      The severity of spasticity, motor function and brace status were evaluated.
      RESULTS: The modified Ashworth Scale (MAS) score of ankle dorsiflexors, range of
      motion, walking speed and balancing ability were significantly improved after
      cycle 1. The improvement of spasticity and motor function was persistent through
      cycles 2-4. One-third of brace users were able to discontinue the use of a brace.
      All of these brace users showed a forward gait pattern prior to therapy.
      CONCLUSIONS: Repeated BoNT-A combined with IR improved lower limb spasticity in
      post-stroke patients. Our results suggest that patients who show the forward gait
      pattern prior to therapy may be able to discontinue the use of their brace after
      therapy.

PMID- 30200282
TI  - Gait Training with Bilateral Rhythmic Auditory Stimulation in Stroke Patients: A
      Randomized Controlled Trial.
AB  - The aim of this study was to investigate the effect of gait training with
      bilateral rhythmic auditory stimulation (RAS) on lower extremity rehabilitation
      in stroke patients. Forty-four participants (<6 months after stroke) were
      randomly allocated to the gait training with bilateral rhythmic auditory
      stimulation (GTBR) group (n = 23) and the control group (n = 21). The GTBR group
      had gait training with bilateral RAS for 30 min a day, 5 days a week, in a 6-week
      period, in addition to conventional therapy. The control group had gait training
      without RAS, and conventional therapy. Outcome measures included gait symmetry,
      gait ability, balance ability, and lower extremity function. Gait symmetry on
      step time showed significant improvements compared to baseline (p < 0.05) in the
      GTBR group, but not in the control group. Gait ability was significantly improved
      in both groups relative to baseline values (p < 0.05), and the GTBR group showed
      significantly greater improvement in comparison to the control group (p < 0.05).
      Both groups showed significant improvements in the Timed Up and Go test (TUG),
      Berg Balance Scale (BBS), and Fugl-Meyer Assessment (FMA) compared to baseline (p
      < 0.05). GTBR is an effective therapeutic method of improving symmetric gait in
      stroke rehabilitation. Moreover, we found that GTBR beat frequency matching fast
      step time might be even more beneficial in improving gait symmetry. Future
      studies may develop a method of applying RAS on step time and length for
      improvement of gait symmetry in stroke patients.

PMID- 30200285
TI  - WiFi Indoor Localization with CSI Fingerprinting-Based Random Forest.
AB  - WiFi fingerprinting indoor positioning systems have extensive applied prospects.
      However, a vast amount of data in a particular environment has to be gathered to
      establish a fingerprinting database. Deficiencies of these systems are the lack
      of universality of multipath effects and a burden of heavy workload on
      fingerprint storage. Thus, this paper presents a novel Random Forest
      fingerprinting localization (RFFP) method using channel state information (CSI),
      which utilizes the Random Forest model trained in the offline stage as
      fingerprints in order to economize memory space and possess a good anti-multipath
      characteristic. Furthermore, a series of specific experiments are conducted in a
      microwave anechoic chamber and an office to detail the localization performance
      of RFFP with different wireless channel circumstances, system parameters,
      algorithms, and input datasets. In addition, compared with other algorithms
      including K-Nearest-Neighbor (KNN), Weighted K-Nearest-Neighbor (WKNN), REPTree,
      CART, and J48, the RFFP method provides far greater classification accuracy as
      well as lower mean location error. The proposed method offers outstanding
      comprehensive performance including accuracy, robustness, low workload, and
      better anti-multipath-fading.

PMID- 30200284
TI  - Correlation between Quality and Geographical Origins of Poria cocos Revealed by
      Qualitative Fingerprint Profiling and Quantitative Determination of Triterpenoid
      Acids.
AB  - Poria cocos (Schw.) Wolf (PC) is a well-known saprophytic fungus, and its
      sclerotium without the epidermis (PCS) is widely used in traditional Chinese
      medicine and as a functional food in many countries. PCS is normally collected
      from multiple geographical regions, but whether and how the quality of PCS
      correlates with where it grows have not been determined. This correlation could
      be significant both for quality control and optimum utilization of PCS as a
      natural resource. In this study, a qualitative fingerprint profiling method
      performed by ultra-performance liquid chromatography (UHPLC) with diode array
      detection (DAD) combining quadrupole time-of-flight-mass spectrometry (QTOF
      MS/MS) and a quantitative UHPLC coupled with triple quadrupole mass spectrometry
      (QqQ-MS/MS) approach were established to investigate whether and how the quality
      of PCS correlates with its collection location. A standard fingerprint of PCS was
      generated by median simulation of 25 tested samples collected from four main
      producing areas of China, and similarity analysis was applied to evaluate the
      similarities between the fingerprints of samples and the standard fingerprint.
      Twenty three common peaks occurring in the fingerprint were unequivocally or
      tentatively identified by UHPLC-QTOF-MS/MS. Meanwhile, principal component
      analysis (PCA), supervised orthogonal partial least squares-discriminate analysis
      (OPLS-DA) and hierarchical cluster analysis (HCA) were employed to classify 25
      batches of PCS samples into four groups, which were highly consistent with the
      four geographical regions. Ten compounds were screened out as potential markers
      to distinguish the quality of PCS. Nine triterpene acids, including five
      compounds that played important roles in the clusters between different samples
      collected from the four collection locations, were simultaneously quantified by
      using the multiple reaction monitoring (MRM) mode of UHPLC-QqQ-MS/MS. The current
      strategy not only clearly expounded the correlation between quality and
      geographical origins of PCS, but also provided a fast, accurate and comprehensive
      qualitative and quantitative method for assessing the quality of PCS.

PMID- 30200283
TI  - Factors Associated with Substance Use and Sexual Behavior among Drug Users in
      Three Mountainous Provinces of Vietnam.
AB  - Due to their geographical characteristics, the mountainous areas of Vietnam are
      particularly vulnerable to illicit drug use. Drug users in remote areas are also
      more likely to engage in risky sexual behaviors. This study aimed to describe the
      prevalence and characteristics of substance use and sexual behaviors and explored
      their related factors among newly admitted drug users in three mountainous
      provinces of Vietnam. A cross-sectional study was conducted on 300 newly-admitted
      drug users registering for Methadone Maintenance Treatment (MMT) at 6 clinics in
      three provinces: Dien Bien, Lai Chau and Yen Bai from October 2014 to December
      2015. Information about the socio-demographic characteristics, history of
      substance use, and sexual behaviors were collected. The multivariate logistic
      regression model was used to identify potential predictors of four outcomes,
      which included: drug injection, re-use of needles, using condoms during the last
      time of having sex, and having sexual intercourse with female sex workers. The
      proportion of injecting drug users was 68.3%; of those 9% never re-used needles.
      Of note, 69% of those who reported having sex with female sex workers in the last
      month did not use condoms. Regression models showed that those who injected drugs
      and had health problems in last 30 days had greater odds of having sex with
      female sex workers. Drug users in mountainous settings acknowledged the high
      prevalence of human immunodeficiency virus (HIV)-related risk behaviors and a
      demand for physical and psychological care. Scaling up MMT services is key to
      approaching this high-risk group; however, at the same time, comprehensive harm
      reduction interventions, counseling, and health care services should also be made
      accessible and effective in this setting.

PMID- 30200280
TI  - Proteomic Approaches for the Discovery of Biofluid Biomarkers of
      Neurodegenerative Dementias.
AB  - Neurodegenerative dementias are highly complex disorders driven by vicious cycles
      of intersecting pathophysiologies. While most can be definitively diagnosed by
      the presence of disease-specific pathology in the brain at postmortem
      examination, clinical disease presentations often involve substantially
      overlapping cognitive, behavioral, and functional impairment profiles that hamper
      accurate diagnosis of the specific disease. As global demographics shift towards
      an aging population in developed countries, clinicians need more sensitive and
      specific diagnostic tools to appropriately diagnose, monitor, and treat
      neurodegenerative conditions. This review is intended as an overview of how
      modern proteomic techniques (liquid chromatography mass spectrometry (LC-MS/MS)
      and advanced capture-based technologies) may contribute to the discovery and
      establishment of better biofluid biomarkers for neurodegenerative disease, and
      the limitations of these techniques. The review highlights some of the more
      interesting technical innovations and common themes in the field but is not
      intended to be an exhaustive systematic review of studies to date. Finally, we
      discuss clear reporting principles that should be integrated into all studies
      going forward to ensure data is presented in sufficient detail to allow
      meaningful comparisons across studies.

PMID- 30200286
TI  - Relative Clinical and Cost Burden of Community-Acquired Pneumonia
      Hospitalizations in Older Adults in the United States-A Cross-Sectional Analysis.
AB  - The relative burden of community-acquired pneumonia (CAP) in older adults (>=65
      years old) compared to other serious diseases is important to prioritize
      preventive treatment. A retrospective analysis was conducted using the 2014
      National Readmission Database to evaluate the length of stay, inpatient
      mortality, 30-day readmissions, and costs of CAP compared to diabetes mellitus
      (DM), myocardial infarction (MI), and stroke. 275,790 hospitalizations were
      analyzed and represented a national estimate of 616,300 hospitalizations,
      including 269,961 for CAP, 71,284 for DM, 126,946 for MI, and 148,109 for stroke.
      The mean length of stay in CAP was 5.2 days, which was higher than DM (4.6) and
      MI (4.3) but similar to stroke (5.6). The inpatient mortality risk was lower for
      DM (RR: 0.37, 95% CI: 0.29-0.46) but higher for MI (RR: 1.67, 95% CI: 1.50-1.85)
      and stroke (RR: 1.67, 95% CI: 1.51-1.83). The median costs for CAP ($7282) were
      higher compared to DM ($6217) but lower compared to MI ($14,802) and stroke
      ($8772). The 30-day readmission rate was 17% in CAP, which was higher compared to
      MI (15%) and stroke (11.5%) and lower compared to DM (20.3%). In patients with
      CAP, disease burden is on par with other serious diseases. CAP should be
      prioritized for prevention in older adults with strategies such as vaccination
      and smoking cessation.

PMID- 30200287
TI  - 5-Hydroxymethylfurfural (HMF) Production from Real Biomasses.
AB  - The present paper reviews recent advances on the direct synthesis of 5
      hydroxymethylfurfural (HMF) from different kinds of raw biomasses. In particular,
      in the paper HMF production from: (i) edible biomasses; (ii) non-edible
      lignocellulosic biomasses; (iii) food wastes (FW) have been reviewed. The
      different processes and catalytic systems have been reviewed and their merits,
      demerits and requirements for commercialisation outlined.

PMID- 30200288
TI  - Central Nervous System Vasculitis for Cryptococcosis in an Immunocompetent
      Patient.
AB  - Cryptococcal meningitis is a life-threatening condition caused by a fungal
      pathogen, Cryptococcus neoformans, that can infect both immunosuppressed and
      immunocompetent hosts. It is an important cause of morbidity and mortality in
      severely immunodeficient patients. However, in an immunocompetent patient it
      represents a diagnostic challenge, mainly because it is extremely rare, but also
      because of its nonspecific clinical manifestation. Neurovascular involvement in
      cryptococcal meningitis is rare and not well known and only few reports have
      described this association. We describe a cryptococcal meningitis in an
      immunocompetent patient associated with central nervous system vasculitis.

PMID- 30200289
TI  - Lateralized Brainstem and Cervical Spinal Cord Responses to Aversive Sounds: A
      Spinal fMRI Study.
AB  - Previous research has delineated the networks of brain structures involved in the
      perception of emotional auditory stimuli. These include the amygdala, insula, and
      auditory cortices, as well as frontal-lobe, basal ganglia, and cerebellar
      structures involved in the planning and execution of motoric behaviors. The aim
      of the current research was to examine whether emotional sounds also influence
      activity in the brainstem and cervical spinal cord. Seventeen undergraduate
      participants completed a spinal functional magnetic resonance imaging (fMRI)
      study consisting of two fMRI runs. One run consisted of three one-minute blocks
      of aversive sounds taken from the International Affective Digitized Sounds (IADS)
      stimulus set; these blocks were interleaved by 40-s rest periods. The other block
      consisted of emotionally neutral stimuli also drawn from the IADS. The results
      indicated a stark pattern of lateralization. Aversive sounds elicited greater
      activity than neutral sounds in the right midbrain and brainstem, and in right
      dorsal and ventral regions of the cervical spinal cord. Neutral stimuli, on the
      other hand, elicited less neural activity than aversive sounds overall; these
      responses were left lateralized and were found in the medial midbrain and the
      dorsal sensory regions of the cervical spinal cord. Together, these results
      demonstrate that aversive auditory stimuli elicit increased sensorimotor
      responses in brainstem and cervical spinal cord structures.

PMID- 30200290
TI  - About One in Five Novice Vapers Buying Their First E-Cigarette in a Vape Shop Are
      Smoking Abstinent after Six Months.
AB  - Background: E-cigarette use is rising with the majority of vapers purchasing
      their e-cigarettes in vape shops. We investigated the smoking/vaping trajectories
      and quit-smoking success rates of smokers deciding to start vaping for the first
      time and buying their e-cigarette in brick-and-mortar vape shops in Flanders.
      Methods: Participants filled out questionnaires assessing smoking/vaping
      behaviour at three moments (intake, after three and six months) and smoking
      status was biochemically verified using eCO measurements. Results: Participants
      (n = 71) were regular smokers (MeCO-intake = 22 ppm), half of whom reported a
      motivation to quit smoking in the near future. Participants bought 3rd/4th
      generation e-cigarettes and e-liquid with a nicotine concentration averaging 7
      mg/mL. A smoking reduction of 53% (17 cigarettes per day (CPD) at intake to 8 CPD
      after six months) was observed, whereas eCO decreased to 15 ppm. Eighteen percent
      of participants had quit smoking completely (eCO = 2 ppm), another 25% had at
      least halved CPD, whereas 57% had failed to reduce CPD by at least 50% (including
      13% lost to follow-up). Quitters consumed more e-liquid than reducers and those
      who continued to smoke. Conclusions: Around one in five smoking customers buying
      their first e-cigarette in a brick-and-mortar vape shop had quit smoking
      completely after six months.

PMID- 30200291
TI  - Evaluation of the Cleaning Procedure Efficacy in Prevention of Nosocomial
      Infections in Healthcare Facilities Using Cultural Method Associated with High
      Sensitivity Luminometer for ATP Detection.
AB  - In healthcare facilities, environmental surfaces may be a reservoir of infectious
      agents even though cleaning and disinfection practices play a role in the control
      of healthcare-associated infections. In this study, the effectiveness of
      cleaning/disinfection procedures has been evaluated in two hospital areas, which
      have different risk category classifications. According to the contract with the
      cleaning service, after the daily ambulatory activities, the housekeeping staff
      apply an alcohol-based detergent followed by a chlorine-based disinfectant (2%
      Antisapril, Angelini; 540 mg/L active chlorine), properly diluted and sprayed.
      The contract provides for the use of disposable microfiber wipes which must be
      replaced with new ones in each health out-patient department. Surface
      contamination was analyzed using cultural methods and ATP detection, performed
      with a high-sensitivity luminometer. The values 100 CFU/cm2 and 40 RLU/cm2 were
      considered as the threshold values for medium-risk category areas, while 250
      CFU/cm2 and 50 RLU/cm2 were defined for the low-risk category ones. Air quality
      was evaluated using active and passive sampling microbiological methods and
      particle count (0.3 MUm-10 MUm) detection. The cleaning/disinfection procedure
      reduced the medium bacterial counts from 32 +/- 56 CFU/cm2 to 2 +/- 3 CFU/cm2 in
      the low-risk area and from 25 +/- 40 CFU/cm2 to 7 +/- 11 CFU/cm2 in the medium
      risk one. Sample numbers exceeding the threshold values decreased from 3% and 13%
      to 1% and 5%, respectively. RLU values also showed a reduction in the samples
      above the thresholds from 76% to 13% in the low-risk area. From the air samples
      collected using the active method, we observed a reduction of 60% in wound care
      and 53% in an ambulatory care visit. From the air samples collected using the
      passive method, we highlighted a 71.4% and 50% reduction in microbial
      contamination in the medium-risk area and in the low-risk one, respectively. The
      10 MUm size particle counts decreased by 52.7% in wound care and by 63% in the
      ambulatory care visit. Correct surface sanitation proved crucial for the
      reduction of microbial contamination in healthcare settings, and plays an
      important role in ensuring air quality in hospital settings.

PMID- 30200292
TI  - Feasibility of Telecom-Wavelength Photonic Integrated Circuits for Gas Sensors.
AB  - To be of commercial interest, gas sensors must optimise, among others,
      sensitivity, selectivity, longevity, cost and measurement speed. Using the
      example of ammonia, we establish that integrated optical sensors provide means to
      maintain the benefits of optical detection set-ups at, in principle, a lower cost
      and smaller footprint than currently available commercial products. Photonic
      integrated circuits (PICs) can be used in environmental and agricultural
      monitoring. The small footprint and great cost scaling of PICs allow for sensor
      networks with multiple devices. We show, that Indium Phosphide based commercial
      foundries reached the technological maturity to enable ammonia detection levels
      at less than 100 ppb. The current unavailability of portable, low cost ammonia
      sensors with such detection levels prevents emission monitoring, for example, in
      pig farms. The feasibility of these sensors is investigated by applying the
      common noise figures of the multiproject wafer platforms operating around 1550 nm
      to a model for an absorption measurement. The analysis is extended to other
      relevant gas species with absorption features near telecom-wavelengths.

PMID- 30200293
TI  - Developmental Programming of the Metabolic Syndrome: Can We Reprogram with
      Resveratrol?
AB  - Metabolic syndrome (MetS) is a mounting epidemic worldwide. MetS can start in
      early life, in a microenvironment that is now known as the developmental origins
      of health and disease (DOHaD). The concept of DOHaD also offers opportunities for
      reprogramming strategies that aim to reverse programming processes in early life.
      Resveratrol, a polyphenolic compound has a wide spectrum of beneficial effects on
      human health. In this review, we first summarize the epidemiological and
      experimental evidence supporting the developmental programming of MetS. This
      review also presents an overview of the evidence linking different molecular
      targets of resveratrol to developmental programming of MetS-related disorders.
      This will be followed by studies documenting resveratrol as a reprogramming agent
      to protect against MetS-related disorders. Further clinical studies are required
      in order to bridge the gap between animal models and clinical trials in order to
      establish the effective dose and therapeutic duration for resveratrol as a
      reprogramming therapy on MetS disorders from developmental origins.

PMID- 30200296
TI  - A Robust Predicted Performance Analysis Approach for Data-Driven Product
      Development in the Industrial Internet of Things.
AB  - Industrial Internet of Things (IoT) is a ubiquitous network integrating various
      sensing technologies and communication technologies to provide intelligent
      information processing and smart control abilities for the manufacturing
      enterprises. The aim of applying industrial IoT is to assist manufacturers manage
      and optimize the entire product manufacturing process to improve product quality
      and production efficiency. Data-driven product development is considered as one
      of the critical application scenarios of industrial IoT, which is used to acquire
      the satisfied and robust design solution according to customer demands.
      Performance analysis is an effective tool to identify whether the key performance
      have reached the requirements in data-driven product development. The existing
      performance analysis approaches mainly focus on the metamodel construction,
      however, the uncertainty and complexity in product development process are rarely
      considered. In response, this paper investigates a robust performance analysis
      approach in industrial IoT environment to help product developers forecast the
      performance parameters accurately. The service-oriented layered architecture of
      industrial IoT for product development is first described. Then a dimension
      reduction approach based on mutual information (MI) and outlier detection is
      proposed. A metamodel based on least squares support vector regression (LSSVR) is
      established to conduct performance prediction process. Furthermore, the predicted
      performance analysis method based on confidence interval estimation is developed
      to deal with the uncertainty to improve the robustness of the forecasting
      results. Finally, a case study is given to show the feasibility and effectiveness
      of the proposed approach.

PMID- 30200295
TI  - Chemical Constituents and Antidepressant-Like Effects in Ovariectomized Mice of
      the Ethanol Extract of Alternanthera philoxeroides.
AB  - The previously unreported flavone glycoside, demethyltorosaflavone B (2) and the
      E-propenoic acid substituted flavone, torosaflavone E (3a), were isolated
      together with nine previously reported metabolites, including indole-3
      carbaldehyde, oleanonic acid, vanillic acid, p-hydroxybenzoic acid, altheranthin
      (1a), alternanthin B (1b), demethyltorosaflavone D (3b), luteolin 8-C-E-propenoic
      acid (4) and chrysoeriol 7-O-rhamnoside (5), from the ethanol extract of the
      aerial part of Althernanthera philoxeroides. The crude ethanol extract was
      evaluated for its in vitro estrogenic activity in MCF-7 breast cancer cell line.
      The crude ethanol extract was also investigated in vivo for its antidepressant
      like effects on ovariectomized mice using tail suspension and forced swimming
      tests, while its effect on the locomotor activity was evaluated by a Y-maze test.
      The effect of the crude extract on the serum corticosterone level, size and
      volume of uterus of the ovariectomized mice were also investigated. The
      expression of the mouse cyclic adenosine monophosphate (cAMP) response element
      binding protein (CREB), brain-derived neurotrophic factor (BDNF) and beta-actin
      mRNAs in hippocampus and frontal cortex was also evaluated, using
      semiquantitative reverse transcription-polymerase chain reaction. The crude
      extract and the isolated compounds 1a, 1b, 3a, 3b and 5, were evaluated for their
      inhibitory effects on monoamine oxidases (MAOs)-A and -B.

PMID- 30200294
TI  - TGF-beta and BMPR2 Signaling in PAH: Two Black Sheep in One Family.
AB  - Knowledge pertaining to the involvement of transforming growth factor beta (TGF
      beta) and bone morphogenetic protein (BMP) signaling in pulmonary arterial
      hypertension (PAH) is continuously increasing. There is a growing understanding
      of the function of individual components involved in the pathway, but a clear
      synthesis of how these interact in PAH is currently lacking. Most of the focus
      has been on signaling downstream of BMPR2, but it is imperative to include the
      role of TGF-beta signaling in PAH. This review gives a state of the art overview
      of disturbed signaling through the receptors of the TGF-beta family with respect
      to vascular remodeling and cardiac effects as observed in PAH. Recent (pre)
      clinical studies in which these two pathways were targeted will be discussed with
      an extended view on cardiovascular research fields outside of PAH, indicating
      novel future perspectives.

PMID- 30200297
TI  - Stakeholder Views on Active Cascade Screening for Familial Hypercholesterolemia.
AB  - In familial hypercholesterolemia (FH), carriers profit from presymptomatic
      diagnosis and early treatment. Due to the autosomal dominant pattern of
      inheritance, first degree relatives of patients are at 50% risk. A program to
      identify healthy relatives at risk of premature cardiovascular problems, funded
      by the Netherlands government until 2014, raised questions on privacy and
      autonomy in view of the chosen active approach of family members. Several
      countries are building cascade screening programs inspired by Dutch experience,
      but meanwhile, the Netherlands' screening program itself is in transition.
      Insight in stakeholders' views on approaching family members is lacking.
      Literature and policy documents were studied, and stakeholders were interviewed
      on pros and cons of actively approaching healthy relatives. Sociotechnical
      analysis explored new roles and responsibilities, with uptake, privacy, autonomy,
      psychological burden, resources, and awareness as relevant themes. Stakeholders
      agree on the importance of early diagnosis and informing the family. Dutch
      healthcare typically focuses on cure, rather than prevention. Barriers to cascade
      screening are paying an own financial contribution, limited resources for
      informing relatives, and privacy regulation. To benefit from predictive,
      personalized, and preventive medicine, the roles and responsibilities of
      stakeholders in genetic testing as a preventive strategy, and informing family
      members, need to be carefully realigned.

PMID- 30200298
TI  - Investigation of Novel Pesticides with Insecticidal and Antifungal Activities:
      Design, Synthesis and SAR Studies of Benzoylpyrimidinylurea Derivatives.
AB  - In order to find pesticides with insecticidal and antifungal activities, a series
      of novel benzoyl pyrimidinylurea derivatives were designed and synthesized. All
      target compounds were identified by 1H-NMR spectroscopy and HRMS. Insecticidal
      and antifungal activity of these compounds were evaluated and the structure
      activity relationships (SAR) were clearly and comprehensively illustrated.
      Compound 7, with low toxicity to zebrafish (LC50 = 378.387 ug mL-1) showed 100%
      inhibition against mosquito (Culex pipiens pallens) at 0.25 ug mL-1. Both
      compounds 19 and 25 exhibited broad-spectrum fungicidal activity (>50% inhibitory
      activities against 13 phytopathogenic fungi), which were better than those of the
      commercial pesticide pyrimethanil (>50% inhibitory activities against eight
      phytopathogenic fungi). Furthermore, compounds 19 and 25 exhibited protective
      activity against Sclerotinia sclerotiorum on leaves of Brassica oleracea L.
      during in vivo experiments.

PMID- 30200300
TI  - The Effect of Set Up Position on EMG Amplitude, Lumbar Spine Kinetics, and Total
      Force Output During Maximal Isometric Conventional-Stance Deadlifts.
AB  - The purpose of this study was to examine the biomechanical differences between
      two set up variations during the isometric initiation of conventional barbell
      deadlifts (DL): Close-bar DL (CBDL), where the bar is positioned above the
      navicular, and far-bar DL (FBDL), where the bar is placed above the 3rd
      metatarsophalangeal joint. A cross-sectional, randomized, within-participant
      pilot study was used. Experienced powerlifters and weightlifters (n = 10)
      performed three individual isometric pulls of the initiation of both conditions.
      The CBDL resulted in lower tibia and knee angles and greater pelvis and torso
      angles than the FBDL (p < 0.05), as well as greater electromyography (EMG)
      activity in the biceps femoris and upper lumbar erector spinae, but lower
      activity in the vastus lateralis, and a lower knee extensor moment (p < 0.05).
      There were no statistical differences for ground reaction force, joint reaction
      lumbar shear and compression forces between the two conditions. Despite the
      differences in pelvis and torso angles between lifting conditions, the internal
      joint net moment, internal shear forces, and internal compressive forces were not
      different between the two lifting styles. The CBDL set up also resulted in
      greater posterior chain (hamstrings and erector spine) EMG amplitude, whereas the
      FBDL set up resulted in more anterior chain (quadriceps) amplitude. Lifters and
      coaches may choose either deadlift style, according to preferences or training
      goals, without concern for differences in lumbar spinal loading.

PMID- 30200299
TI  - Combined Modulation of Tumor Metabolism by Metformin and Diclofenac in Glioma.
AB  - Glioblastoma remains a fatal diagnosis. Previous research has shown that
      metformin, which is an inhibitor of complex I of the respiratory chain, may
      inhibit some brain tumor initiating cells (BTICs), albeit at dosages that are too
      high for clinical use. Here, we explored whether a combined treatment of
      metformin and diclofenac, which is a non-steroidal anti-inflammatory drug (NSAID)
      shown to inhibit glycolysis by interfering with lactate efflux, may lead to
      additive or even synergistic effects on BTICs (BTIC-8, -11, -13 and -18) and
      tumor cell lines (TCs, U87, and HTZ349). Therefore, we investigated the
      functional effects, including proliferation and migration, metabolic effects
      including oxygen consumption and extracellular lactate levels, and effects on the
      protein level, including signaling pathways. Functional investigation revealed
      synergistic anti-migratory and anti-proliferative effects of the combined
      treatment with metformin and diclofenac on BTICs and TCs. Signaling pathways did
      not sufficiently explain synergistic effects. However, we observed that metformin
      inhibited cellular oxygen consumption and increased extracellular lactate levels,
      indicating glycolytic rescue mechanisms. Combined treatment inhibited metformin
      induced lactate increase. The combination of metformin and diclofenac may
      represent a promising new strategy in the treatment of glioblastoma. Combined
      treatment may reduce the effective doses of the single agents and prevent
      metabolic rescue mechanisms. Further studies are needed in order to determine
      possible side effects in humans.

PMID- 30200301
TI  - Transient Receptor Potential Channel A1 (TRPA1) Regulates Sulfur Mustard-Induced
      Expression of Heat Shock 70 kDa Protein 6 (HSPA6) In Vitro.
AB  - The chemosensory transient receptor potential ankyrin 1 (TRPA1) ion channel
      perceives different sensory stimuli. It also interacts with reactive exogenous
      compounds including the chemical warfare agent sulfur mustard (SM). Activation of
      TRPA1 by SM results in elevation of intracellular calcium levels but the cellular
      consequences are not understood so far. In the present study we analyzed SM
      induced and TRPA1-mediated effects in human TRPA1-overexpressing HEK cells
      (HEKA1) and human lung epithelial cells (A549) that endogenously exhibit TRPA1.
      The specific TRPA1 inhibitor AP18 was used to distinguish between SM-induced and
      TRPA1-mediated or TRPA1-independent effects. Cells were exposed to 600 uM SM and
      proteome changes were investigated 24 h afterwards by 2D gel electrophoresis.
      Protein spots with differential staining levels were analyzed by matrix-assisted
      laser desorption/ionization time-of-flight mass spectrometry and nano liquid
      chromatography electrospray ionization tandem mass spectrometry. Results were
      verified by RT-qPCR experiments in both HEKA1 or A549 cells. Heat shock 70 kDa
      protein 6 (HSPA6) was identified as an SM-induced and TRPA1-mediated protein.
      AP18 pre-treatment diminished the up-regulation. RT-qPCR measurements verified
      these results and further revealed a time-dependent regulation. Our results
      demonstrate that SM-mediated activation of TRPA1 influences the protein
      expression and confirm the important role of TRPA1 ion channels in the molecular
      toxicology of SM.

PMID- 30200304
TI  - Extraction of High-Precision Urban Impervious Surfaces from Sentinel-2
      Multispectral Imagery via Modified Linear Spectral Mixture Analysis.
AB  - This study explores the performance of Sentinel-2A Multispectral Instrument (MSI)
      imagery for extracting urban impervious surface using a modified linear spectral
      mixture analysis (MLSMA) method. Sentinel-2A MSI provided 10 m red, green, blue,
      and near-infrared spectral bands, and 20 m shortwave infrared spectral bands,
      which were used to extract impervious surfaces. We aimed to extract urban
      impervious surfaces at a spatial resolution of 10 m in the main urban area of
      Guangzhou, China. In MLSMA, a built-up image was first extracted from the
      normalized difference built-up index (NDBI) using the Otsu's method; the high
      albedo, low-albedo, vegetation, and soil fractions were then estimated using
      conventional linear spectral mixture analysis (LSMA). The LSMA results were post
      processed to extract high-precision impervious surface, vegetation, and soil
      fractions by integrating the built-up image and the normalized difference
      vegetation index (NDVI). The performance of MLSMA was evaluated using Landsat 8
      Operational Land Imager (OLI) imagery. Experimental results revealed that MLSMA
      can extract the high-precision impervious surface fraction at 10 m with Sentinel
      2A imagery. The 10 m impervious surface map of Sentinel-2A is capable of
      recovering more detail than the 30 m map of Landsat 8. In the Sentinel-2A
      impervious surface map, continuous roads and the boundaries of buildings in urban
      environments were clearly identified.

PMID- 30200303
TI  - A Simple Method for On-Gel Detection of Myrosinase Activity.
AB  - Myrosinase is an enzyme present in many functional foods and spices, particularly
      in Cruciferous vegetables. It hydrolyses glucosinolates which thereafter
      rearrange into bioactive volatile constituents (isothiocyanates, nitriles). We
      aimed to develop a simple reversible method for on-gel detection of myrosinase.
      Reagent composition and application parameters for native PAGE and SDS-PAGE gels
      were optimized. The proposed method was successfully applied to detect myrosinase
      (or sulfatase) on-gel: the detection solution contains methyl red which gives
      intensive red bands where the HSO4- is enzymatically released from the
      glucosinolates. Subsequently, myrosinase was successfully distinguished from
      sulfatase by incubating gel bands in a derivatization solution and examination by
      LC-ESI-MS: myrosinase produced allyl isothiocyanate (detected in conjugate form)
      while desulfo-sinigrin was released by sulfatase, as expected. After separation
      of 80 ug protein of crude extracts of Cruciferous vegetables, intensive color
      develops within 10 min. On-gel detection was found to be linear between 0.031
      0.25 U (pure Sinapis alba myrosinase, R2 = 0.997). The method was successfully
      applied to detection of myrosinase isoenzymes from horseradish, Cruciferous
      vegetables and endophytic fungi of horseradish as well. The method was shown to
      be very simple, rapid and efficient. It enables detection and partial
      characterization of glucosinolate decomposing enzymes without protein
      purification.

PMID- 30200305
TI  - Blind UAV Images Deblurring Based on Discriminative Networks.
AB  - Unmanned aerial vehicles (UAVs) have become an important technology for acquiring
      high-resolution remote sensing images. Because most space optical imaging systems
      of UAVs work in environments affected by vibrations, the optical axis motion and
      image plane jitter caused by these vibrations easily result in blurring of UAV
      images. In the paper; we propose an advanced UAV image deblurring method based on
      a discriminative model comprising a classifier for blurred and sharp UAV images
      which is embedded into the maximum a posteriori framework as a regularization
      term that constantly optimizes ill-posed problem of blind image deblurring to
      obtain sharper UAV images. Compared with other methods, the results show that in
      image deblurring experiments using both simulated and real UAV images the
      proposed method delivers sharper images of various ground objects.

PMID- 30200302
TI  - NF-kappaB, Mesenchymal Differentiation and Glioblastoma.
AB  - Although glioblastoma (GBM) has always been recognized as a heterogeneous tumor,
      the advent of largescale molecular analysis has enabled robust categorization of
      this malignancy into several specific subgroups. Among the subtypes designated by
      expression profiling, mesenchymal tumors have been associated with an
      inflammatory microenvironment, increased angiogenesis, and resistance to therapy.
      Nuclear factor-kappaB (NF-kappaB) is a ubiquitous transcription factor that plays
      a prominent role in mediating many of the central features associated with
      mesenchymal differentiation. This review summarizes the mechanisms by which NF
      kappaB proteins and their co-regulating partners induce the transcriptional
      network that underlies the mesenchymal phenotype. Moreover, both the intrinsic
      changes within mesenchymal GBM cells and the microenvironmental factors that
      modify the overall NF-kappaB response are detailed.

PMID- 30200306
TI  - Effect of Metal Thickness on the Sensitivity of Crack-Based Sensors.
AB  - Among many attempts to make a decent human motion detector in various engineering
      fields, a mechanical crack-based sensor that deliberately generates and uses nano
      scale cracks on a metal deposited thin film is gaining attention for its high
      sensitivity. While the metal layer of the sensor must be responsible for its high
      performance, its effects have not received much academic interest. In this paper,
      we studied the relationship between the thickness of the metal layer and the
      characteristics of the sensor by depositing a few nanometers of chromium (Cr) and
      gold (Au) on the PET film. We found that the sensitivity of the crack sensor
      improves/increases under the following conditions: (1) when Au is thin and Cr is
      thick; and (2) when the ratio of Au is lower than that of Cr, which also
      increases the transmittance of the sensor, along with its sensitivity. As we only
      need a small amount of Au to achieve high sensitivity of the sensor, we have
      suggested more efficient and economical fabrication methods. With this crack
      based sensor, we were able to successfully detect finger motions and to
      distinguish various signs of American Sign Language (ASL).

PMID- 30200308
TI  - SWCTI: Surface Water Content Temperature Index for Assessment of Surface Soil
      Moisture Status.
AB  - The vegetation supply water index (VSWI = NDVI/LST) is an effective metric
      estimating soil moisture in areas with moderate to dense vegetation cover.
      However, the normalized difference vegetation index (NDVI) exhibits a long water
      stress lag and the land surface temperature (LST), sensitive to water stress,
      does not contribute considerably to surface soil moisture monitoring due to the
      constraints of the mathematical characteristics of VSWI: LST influences VSWI less
      when LST value is sufficiently high. This paper mathematically analyzes the
      characteristics of VSWI and proposes a new operational dryness index (surface
      water content temperature index, SWCTI) for the assessment of surface soil
      moisture status. SWCTI uses the surface water content index (SWCI), which
      provides a more accurate estimation of surface soil moisture than that of NDVI,
      as the numerator and the modified surface temperature, which has a greater
      influence on SWCTI than that of LST, as the denominator. The validation work
      includes comparison of SWCTI with in situ soil moisture and other remote sensing
      indices. The results show SWCTI demonstrates the highest correlation with in situ
      soil moisture; the highest correlation R = 0.801 is found between SWCTI and the 0
      5 cm soil moisture in a sandy loam. SWCTI is a functional and effective method
      that has a great potential in surface soil moisture monitoring.

PMID- 30200309
TI  - Biobased Functional Carbon Materials: Production, Characterization, and
      Applications-A Review.
AB  - Even though research on porous carbon materials from biomass dates back to at
      least hundred years, it is still an extremely relevant topic. These materials can
      be found in applications that range from those that are widely known, such as
      water treatment, to others that are newer and indispensable for the transition
      towards environmentally friendly technologies, such as lithium- and sodium-ion
      batteries. This review summarizes some of the most relevant research that has
      been published concerning production technologies, insights on the chemical
      reaction mechanisms, characterization techniques, as well as some examples of the
      applications and the properties that the carbon materials must fulfil to be used
      in those applications.

PMID- 30200307
TI  - Assessment of Health Information Technology Interventions in Evidence-Based
      Medicine: A Systematic Review by Adopting a Methodological Evaluation Framework.
AB  - BACKGROUND: The application of Health Information Technologies (HITs) can be an
      effective way to advance medical research and health services provision. The two
      fold objective of this work is to: (i) identify and review state-of-the-art HITs
      that facilitate the aims of evidence-based medicine and (ii) propose a
      methodology for HIT assessment. METHODS: The systematic review was conducted
      according to the Preferred Reporting Items for Systematic Reviews and Meta
      Analyses (PRISMA) guidelines. Furthermore, we consolidated existing knowledge in
      the field and proposed a Synthesis Framework for the Assessment of Health
      Information Technology (SF/HIT) in order to evaluate the joint use of Randomized
      Controlled Trials (RCTs) along with HITs in the field of evidence-based medicine.
      RESULTS: 55 articles met the inclusion criteria and refer to 51 (RCTs) published
      between 2008 and 2016. Significant improvements in healthcare through the use of
      HITs were observed in the findings of 31 out of 51 trials-60.8%. We also
      confirmed that RCTs are valuable tools for assessing the effectiveness,
      acceptability, safety, privacy, appropriateness, satisfaction, performance,
      usefulness and adherence. CONCLUSIONS: To improve health service delivery, RCTs
      apply and exhibit formalization by providing measurable outputs. Towards this
      direction, we propose the SF/HIT as a framework which may help researchers to
      carry out appropriate evaluations and extend their studies.

PMID- 30200310
TI  - Genotyping-by-Sequencing Enhances Genetic Diversity Analysis of Crested
      Wheatgrass [Agropyron cristatum (L.) Gaertn.].
AB  - Molecular characterization of unsequenced plant species with complex genomes is
      now possible by genotyping-by-sequencing (GBS) using recent next generation
      sequencing technologies. This study represents the first use of GBS application
      to sample genome-wide variants of crested wheatgrass [Agropyron cristatum (L.)
      Gaertn.] and assess the genetic diversity present in 192 genotypes from 12
      tetraploid lines. Bioinformatic analysis identified 45,507 single nucleotide
      polymorphism (SNP) markers in this outcrossing grass species. The model-based
      Bayesian analysis revealed four major clusters of the samples assayed. The
      diversity analysis revealed 15.8% of SNP variation residing among the 12 lines,
      and 12.1% SNP variation present among four genetic clusters identified by the
      Bayesian analysis. The principal coordinates analysis and dendrogram were able to
      distinguish four lines of Asian origin from Canadian cultivars and breeding
      lines. These results serve as a valuable resource for understanding genetic
      variability, and will aid in the genetic improvement of this outcrossing
      polyploid grass species for forage production. These findings illustrate the
      potential of GBS application in the characterization of non-model polyploid
      plants with complex genomes.

PMID- 30200311
TI  - Automatic Outcome in Manual Dexterity Assessment Using Colour Segmentation and
      Nearest Neighbour Classifier.
AB  - Objective assessment of motor function is an important component to evaluating
      the effectiveness of a rehabilitation process. Such assessments are carried out
      by clinicians using traditional tests and scales. The Box and Blocks Test (BBT)
      is one such scale, focusing on manual dexterity evaluation. The score is the
      maximum number of cubes that a person is able to displace during a time window.
      In a previous paper, an automated version of the Box and Blocks Test using a
      Microsoft Kinect sensor was presented, and referred to as the Automated Box and
      Blocks Test (ABBT). In this paper, the feasibility of ABBT as an automated tool
      for manual dexterity assessment is discussed. An algorithm, based on image
      segmentation in CIELab colour space and the Nearest Neighbour (NN) rule, was
      developed to improve the reliability of automatic cube counting. A pilot study
      was conducted to assess the hand motor function in people with Parkinson's
      disease (PD). Three functional assessments were carried out. The success rate in
      automatic cube counting was studied by comparing the manual (BBT) and the
      automatic (ABBT) methods. The additional information provided by the ABBT was
      analysed to discuss its clinical significance. The results show a high
      correlation between manual (BBT) and automatic (ABBT) scoring. The lowest average
      success rate in cube counting for ABBT was 92%. Additionally, the ABBT acquires
      extra information from the cubes' displacement, such as the average velocity and
      the time instants in which the cube was detected. The analysis of this
      information can be related to indicators of health status (coordination and
      dexterity). The results showed that the ABBT is a useful tool for automating the
      assessment of unilateral gross manual dexterity, and provides additional
      information about the user's performance.

PMID- 30200313
TI  - p-Value Histograms: Inference and Diagnostics.
AB  - It is increasingly common for experiments in biology and medicine to involve
      large numbers of hypothesis tests. A natural graphical method for visualizing
      these tests is to construct a histogram from the p-values of these tests. In this
      article, we examine the shapes, both regular and irregular, that these histograms
      can take on, as well as present simple inferential procedures that help to
      interpret the shapes in terms of diagnosing potential problems with the
      experiment. We examine potential causes of these problems in detail, and discuss
      potential remedies. Throughout, examples of irregular-looking p-value histograms
      are provided and based on case studies involving real biological experiments.

PMID- 30200315
TI  - Annoyance in Response to Vibrations from Railways.
AB  - Rail transport is a key stepping stone in the EU's transport policy and is
      pinpointed for investment and growth over the coming decades. This expanding
      infrastructure implies increased exposure to environmental stressors, such as
      noise and ground-borne vibrations. Little is known about the health impacts of
      exposure to these vibrations. The aim of this paper is to examine the association
      between annoyance from rail vibrations and the distance of residential dwelling
      from the railway. It reports the first results of a large epidemiological study,
      EpiVib, which was designed to investigate the long-term health effects of
      exposure to rail vibrations. The first part of this study examines a self
      reported questionnaire. In total, 6894 individuals aged between 18 and 80 living
      within 1 km of a railway in west Sweden participated. Results presented here
      examine the association between distance to the railway and annoyance from
      vibrations and are stratified by train type. A positive association between
      closer distance and increased annoyance is seen. After adjustment for important
      modifiers, results showed that vibrations from freight trains and maintenance
      operations are reported to be moderately and highly annoying at distances of up
      to 400 m from the railway and diesel up to 300 m. Vibration from passenger and
      fast trains are significantly annoying up to 200 m from the track. Vibration from
      freight trains and maintenance operations were considered highly annoying up to
      300 m from the track, diesel up to 400 m. Vibration from passenger and fast
      trains are not reported to be highly annoying after adjustment. Heavier, slower
      moving locomotives, in the form of diesel and freight trains, appear to be the
      source of annoyance at distances further from the railway compared to passenger
      and fast trains. This has implications in terms of property, transport, and
      infrastructure planning.

PMID- 30200312
TI  - Barcoding of Plant Viruses with Circular Single-Stranded DNA Based on Rolling
      Circle Amplification.
AB  - The experience with a diagnostic technology based on rolling circle amplification
      (RCA), restriction fragment length polymorphism (RFLP) analyses, and direct or
      deep sequencing (Circomics) over the past 15 years is surveyed for the plant
      infecting geminiviruses, nanoviruses and associated satellite DNAs, which have
      had increasing impact on agricultural and horticultural losses due to global
      transportation and recombination-aided diversification. Current state methods for
      quarantine measures are described to identify individual DNA components with
      great accuracy and to recognize the crucial role of the molecular viral
      population structure as an important factor for sustainable plant protection.

PMID- 30200316
TI  - Acupuncture and Lifestyle Myopia in Primary School Children-Results from a
      Transcontinental Pilot Study Performed in Comparison to Moxibustion.
AB  - Background: Lifestyle risks for myopia are well known and the disease has become
      a major global public health issue worldwide. There is a relation between
      reading, writing, and computer work and the development of myopia. Methods:
      Within this prospective pilot study in 44 patients aged between 6 and 12 years
      with myopia we compared possible treatment effects of acupuncture or moxibustion.
      The diopters of the right and left eye were evaluated before and after the two
      treatment methods. Results: Myopia was improved in 14 eyes of 13 patients (15.9%)
      within both complementary methods. Using acupuncture an improvement was observed
      in seven eyes from six patients out of 22 patients and a similar result
      (improvement in seven eyes from seven patients out of 22 patients) was noticed in
      the moxibustion group. The extent of improvement was better in the acupuncture
      group (p = 0.008 s., comparison before and after treatment); however, group
      analysis between acupuncture and moxibustion revealed no significant difference.
      Conclusions: Possible therapeutic aspects with the help of evidence-based
      complementary methods like acupuncture or moxibustion have not yet been
      investigated adequately in myopic patients. Our study showed that both
      acupuncture and moxibustion can improve myopia of young patients. Acupuncture
      seems to be more effective than moxibustion in treating myopia, however group
      analysis did not prove this trend. Therefore, further Big data studies are
      necessary to confirm or refute the preliminary results.

PMID- 30200317
TI  - Analysis of Green Public Procurement of Works by Spanish Public Universities.
AB  - Universities play an important role among public institutions because they
      initiate huge purchasing and contracting activities and contribute to sustainable
      development through education, research, and day-to-day operations. Existing
      studies on green public procurement (GPP) practices at Spanish universities focus
      on products and services. For this study, a total of 316 procedures were
      collected and analysed from the calls for tenders made by Spanish public
      universities between 2016 and 2017. The environmental criteria involved in the
      tenders and their weights were classified by subsector, geographical scope, and
      project budget. The results of this study show the use of environmental criteria
      in the works tendered by Spanish public universities is low (19.2%) in comparison
      with the results of other studies. It is therefore necessary to encourage GPP
      practices in the contracting process to comply with the environmental policies
      that universities have defined as part of their institutional policies.

PMID- 30200314
TI  - Application of Dendrimers for the Treatment of Infectious Diseases.
AB  - Dendrimers are drug delivery systems that are characterized by a three
      dimensional, star-shaped, branched macromolecular network. They possess ideal
      properties such as low polydispersity index, biocompatibility and good water
      solubility. They are made up of the interior and the exterior layers. The
      exterior layer consists of functional groups that are useful for conjugation of
      drugs and targeting moieties. The interior layer exhibits improved drug
      encapsulation efficiency, reduced drug toxicity, and controlled release
      mechanisms. These unique properties make them useful for drug delivery.
      Dendrimers have attracted considerable attention as drug delivery system for the
      treatment of infectious diseases. The treatment of infectious diseases is
      hampered severely by drug resistance. Several properties of dendrimers such as
      their ability to overcome drug resistance, toxicity and control the release
      mechanism of the encapsulated drugs make them ideal systems for the treatment of
      infectious disease. The aim of this review is to discuss the potentials of
      dendrimers for the treatment of viral and parasitic infections.

PMID- 30200318
TI  - Structural Prediction of the Dimeric Form of the Mammalian Translocator Membrane
      Protein TSPO: A Key Target for Brain Diagnostics.
AB  - Positron emission tomography (PET) radioligands targeting the human translocator
      membrane protein (TSPO) are broadly used for the investigations of
      neuroinflammatory conditions associated with neurological disorders. Structural
      information on the mammalian protein homodimers-the suggested functional state of
      the protein-is limited to a solid-state nuclear magnetic resonance (NMR) study
      and to a model based on the previously-deposited solution NMR structure of the
      monomeric mouse protein. Computational studies performed here suggest that the
      NMR-solved structure in the presence of detergents is not prone to dimer
      formation and is furthermore unstable in its native membrane environment. We,
      therefore, propose a new model of the functionally-relevant dimeric form of the
      mouse protein, based on a prokaryotic homologue. The model, fully consistent with
      solid-state NMR data, is very different from the previous predictions. Hence, it
      provides, for the first time, structural insights into this pharmaceutically
      important target which are fully consistent with experimental data.

PMID- 30200319
TI  - Porous Silicon-Based Catalysts for the Dehydration of Glycerol to High Value
      Added Products.
AB  - Increasing worldwide biodiesel production has led to the generation of an
      important glycerol surplus, which needs to be valorized in order to improve the
      economic and environmental sustainability of the biodiesel industry. In this
      context, glycerol dehydration to acrolein by acid catalysis appears to be a
      potential route of glycerol valorization, since acrolein is an important
      intermediate for many chemical industries. The main drawback of this catalytic
      process is catalyst deactivation. Different alternatives have been proposed for
      overcoming it, such as the use of mesoporous materials in order to facilitate the
      diffusion of glycerol and reaction products, thus minimizing deactivation. This
      review compiles the main achievements of the use of mesoporous silica-containing
      materials that have been deployed either as a catalyst or for support in glycerol
      dehydration to acrolein. Thus, the effect of mesoporosity on both catalytic
      performance and deactivation will be discussed, as well as the blocking of pores
      by coke deposition.

PMID- 30200320
TI  - Atrazine Contamination of Drinking Water and Adverse Birth Outcomes in Community
      Water Systems with Elevated Atrazine in Ohio, 2006-2008.
AB  - Atrazine, a common water contaminant in the U.S., has been associated with
      adverse birth outcomes in previous studies. This study aimed to determine if
      atrazine concentrations in drinking water are associated with adverse birth
      outcomes including small for gestational age (SGA), term low birth weight (term
      LBW), very low birth weight (VLBW), preterm birth (PTB), and very preterm birth
      (VPTB). This study included 14,445 live singleton births from Ohio communities
      served by 22 water systems enrolled in the U.S. Environmental Protection Agency's
      Atrazine Monitoring Program between 2006 and 2008. Mean gestational and trimester
      specific atrazine concentrations were calculated. Significantly increased odds of
      term LBW birth was associated with atrazine exposure over the entire gestational
      period (OR 1.27, 95% CI 1.10, 1.45), as well as the first (OR 1.20, 95% CI 1.08,
      1.34) and second trimesters (OR 1.13, 95% CI 1.07, 1.20) of pregnancy. We
      observed no evidence of an association between atrazine exposure via drinking
      water and SGA, VLBW, PTB, or VPTB. Our results suggest that atrazine exposure is
      associated with reduced birth weight among term infants and that exposure to
      atrazine in drinking water in early and mid-pregnancy may be most critical for
      its toxic effects on the fetus.

PMID- 30200321
TI  - A Motivational Model of BCI-Controlled Heuristic Search.
AB  - Several researchers have proposed a new application for human augmentation, which
      is to provide human supervision to autonomous artificial intelligence (AI)
      systems. In this paper, we introduce a framework to implement this proposal,
      which consists of using Brain-Computer Interfaces (BCI) to influence AI
      computation via some of their core algorithmic components, such as heuristic
      search. Our framework is based on a joint analysis of philosophical proposals
      characterising the behaviour of autonomous AI systems and recent research in
      cognitive neuroscience that support the design of appropriate BCI. Our framework
      is defined as a motivational approach, which, on the AI side, influences the
      shape of the solution produced by heuristic search using a BCI motivational
      signal reflecting the user's disposition towards the anticipated result. The
      actual mapping is based on a measure of prefrontal asymmetry, which is translated
      into a non-admissible variant of the heuristic function. Finally, we discuss
      results from a proof-of-concept experiment using functional near-infrared
      spectroscopy (fNIRS) to capture prefrontal asymmetry and control the progression
      of AI computation of traditional heuristic search problems.

PMID- 30200322
TI  - A New Chemoenzymatic Synthesis of the Chiral Key Intermediate of the
      Antiepileptic Brivaracetam.
AB  - Brivaracetam is a new anticonvulsant compound, recently approved as an
      antiepileptic drug. This drug substance presents a 4-substituted pyrrolidone
      structure: the (4R)-configuration of the stereocenter present on the heterocyclic
      ring is the main target of the synthesis. The described method allows to prepare
      the suitable optically pure 2-substituted primary alcohol by means of a
      Pseudomonas fluorescens lipase-catalyzed transesterification. The obtained (2R)
      alcohol was easily transformed into the (3R)-3-propylbutyrolactone, an advanced
      intermediate of brivaracetam. The described synthetic pathway is completed with
      the chromatographic methods and the NMR analyses necessary to establish the
      chemical and the optical purity of the intermediates and of the final lactone.

PMID- 30200323
TI  - Protective Properties of a Microstructure Composed of Barrier Nanostructured
      Organics and SiOx Layers Deposited on a Polymer Matrix.
AB  - The SiOx barrier nanocoatings have been prepared on selected polymer matrices to
      increase their resistance against permeation of toxic substances. The aim has
      been to find out whether the method of vacuum plasma deposition of SiOx barrier
      nanocoatings on a polyethylene terephthalate (PET) foil used by Aluminium Company
      of Canada (ALCAN) company (ALCAN Packaging Kreuzlingen AG (SA/Ltd., Kreuzlingen,
      Switzerland) within the production of CERAMIS(r) packaging materials with barrier
      properties can also be used to increase the resistance of foils from other
      polymers against the permeation of organic solvents and other toxic liquids. The
      scanning electron microscopy (SEM) microstructure of SiOx nanocoatings prepared
      by thermal deposition from SiO in vacuum by the Plasma Assisted Physical Vapour
      Deposition (PA-PVD) method or vacuum deposition of hexamethyldisiloxane (HMDSO)
      by the Plasma-enhanced chemical vapour deposition (PECVD) method have been
      studied. The microstructure and behavior of samples when exposed to a liquid test
      substance in relation to the barrier properties is described.

PMID- 30200324
TI  - Heavy Metal Contamination Near Industrial Estate Areas in Phra Nakhon Si
      Ayutthaya Province, Thailand and Human Health Risk Assessment.
AB  - Industrial activity is one of the significant sources of environmental
      contamination with heavy metals, especially in developing countries. Flood can
      also lead to the distribution of toxic substances into the environment, regarding
      the Thailand flood in 2011 as some industrial estates are affected, leading to
      concern about heavy metals from industrial wastewater contamination. We aimed to
      measure the levels of Cd, Cr, Cu, Ni, Mn, Pb, and Zn in river and stream water,
      sediment, and fish collected from the area around the industrial estates in Uthai
      District and Bangpa-in District of Phra Nakhon Si Ayutthaya Province, following
      the floods of 2011. The results revealed that heavy metal levels in water did not
      exceed Thailand surface water quality standards, except for Mn levels at one
      sampling site. Metal levels in sediment and fish samples also did not exceed
      published standards. The hazard quotient for fish consumption was highest for Ni
      (0.2178) in Trichopodus trichopterus collected from the area near the industrial
      estate in Bangpa-in District, while the hazard index from Cd, Cr, and Cu exposure
      were 0.86966, which was lower than 1, indicating that the health risks for these
      seven metals were within acceptable ranges.

PMID- 30200327
TI  - Practical Use of Robot Manipulators as Intelligent Manufacturing Systems.
AB  - This paper presents features and advanced settings for a robot manipulator
      controller in a fully interconnected intelligent manufacturing system. Every
      system is made up of different agents. As also occurs in the Internet of Things
      and smart cities, the big issue here is to ensure not only that implementation is
      key, but also that there is better common understanding among the main players.
      The commitment of all agents is still required to translate that understanding
      into practice in Industry 4.0. Mutual interactions such as machine-to-machine and
      man-to-machine are solved in real time with cyber physical capabilities. This
      paper explores intelligent manufacturing through the context of industrial robot
      manipulators within a Smart Factory. An online communication algorithm with
      proven intelligent manufacturing abilities is proposed to solve real-time
      interactions. The algorithm is developed to manage and control all robot
      parameters in real-time. The proposed tool in conjunction with the intelligent
      manufacturing core incorporates data from the robot manipulators into the
      industrial big data to manage the factory. The novelty is a communication tool
      that implements the Industry 4.0 standards to allow communications among the
      required entities in the complete system. It is achieved by the developed tool
      and implemented in a real robot and simulation.

PMID- 30200325
TI  - Cys2/His2 Zinc-Finger Proteins in Transcriptional Regulation of Flower
      Development.
AB  - Flower development is the core of higher-plant ontogenesis and is controlled by
      complex gene regulatory networks. Cys2/His2 zinc-finger proteins (C2H2-ZFPs)
      constitute one of the largest transcription factor families and are highly
      involved in transcriptional regulation of flowering induction, floral organ
      morphogenesis, and pollen and pistil maturation. Nevertheless, the molecular
      mechanism of C2H2-ZFPs has been gradually revealed only in recent years. During
      flowering induction, C2H2-ZFPs can modify the chromatin of FLOWERING LOCUS C,
      thereby providing additional insights into the quantification of transcriptional
      regulation caused by chromatin regulation. C2H2-ZFPs are involved in cell
      division and proliferation in floral organ development and are associated with
      hormonal regulation, thereby revealing how a flower is partitioned into four
      developmentally distinct whorls. The studies reviewed in this work integrate the
      information from the endogenous, hormonal, and environmental regulation of flower
      development. The structure of C2H2-ZFPs determines their function as
      transcriptional regulators. The findings indicate that C2H2-ZFPs play a crucial
      role in flower development. In this review, we summarize the current
      understanding of the structure, expression, and function of C2H2-ZFPs and discuss
      their molecular mechanism in flower development.

PMID- 30200328
TI  - Improving the Performance of Multi-GNSS Time and Frequency Transfer Using Robust
      Helmert Variance Component Estimation.
AB  - The combination of multiple Global Navigation Satellite Systems (GNSSs) may
      improve the performance of time and frequency transfers by increasing the number
      of available satellites and improving the time dilution of precision. However,
      the receiver clock estimation is easily affected by the inappropriate weight of
      multi-GNSSs due to the different characteristics of individual GNSS signals as
      well as the outliers from observations. Thus, we utilised a robust Helmert
      variance component estimation (RVCE) approach to determine the appropriate
      weights of different GNSS observations, and to control for the influence of
      outliers in these observation in multi-GNSS time and frequency transfer. In order
      to validate the effectiveness of this approach, four time links were employed.
      Compared to traditional solutions, the mean improvement of smoothed residuals is
      3.43% using the RVCE approach. With respect to the frequency stability of the
      time links, the RVCE solution outperforms the traditional solution, particularly
      in the short-term, and the mean improvement is markedly high at 14.89%.

PMID- 30200326
TI  - Injured Achilles Tendons Treated with Adipose-Derived Stem Cells Transplantation
      and GDF-5.
AB  - Tendon injuries represent a clinical challenge in regenerative medicine because
      their natural repair process is complex and inefficient. The high incidence of
      tendon injuries is frequently associated with sports practice, aging,
      tendinopathies, hypertension, diabetes mellitus, and the use of corticosteroids.
      The growing interest of scientists in using adipose-derived mesenchymal stem
      cells (ADMSC) in repair processes seems to be mostly due to their paracrine and
      immunomodulatory effects in stimulating specific cellular events. ADMSC activity
      can be influenced by GDF-5, which has been successfully used to drive tenogenic
      differentiation of ADMSC in vitro. Thus, we hypothesized that the application of
      ADMSC in isolation or in association with GDF-5 could improve Achilles tendon
      repair through the regulation of important remodeling genes expression. Lewis
      rats had tendons distributed in four groups: Transected (T), transected and
      treated with ADMSC (ASC) or GDF-5 (GDF5), or with both (ASC+GDF5). In the
      characterization of cells before application, ADMSC expressed the positive
      surface markers, CD90 (90%) and CD105 (95%), and the negative marker, CD45 (7%).
      ADMSC were also differentiated in chondrocytes, osteoblast, and adipocytes. On
      the 14th day after the tendon injury, GFP-ADMSC were observed in the transected
      region of tendons in the ASC and ASC+GDF5 groups, and exhibited and/or stimulated
      a similar genes expression profile when compared to the in vitro assay. ADMSC up
      regulated Lox, Dcn, and Tgfb1 genes expression in comparison to T and ASC+GDF5
      groups, which contributed to a lower proteoglycans arrangement, and to a higher
      collagen fiber organization and tendon biomechanics in the ASC group. The
      application of ADMSC in association with GDF-5 down-regulated Dcn, Gdf5, Lox,
      Tgfb1, Mmp2, and Timp2 genes expression, which contributed to a lower
      hydroxyproline concentration, lower collagen fiber organization, and to an
      improvement of the rats' gait 24 h after the injury. In conclusion, although the
      literature describes the benefic effect of GDF-5 for the tendon healing process,
      our results show that its application, isolated or associated with ADMSC, cannot
      improve the repair process of partial transected tendons, indicating the higher
      effectiveness of the application of ADMSC in injured Achilles tendons. Our
      results show that the application of ADMSC in injured Achilles tendons was more
      effective in relation to its association with GDF-5.

PMID- 30200330
TI  - Cytotoxic Desulfated Saponin from Holothuria atra Predicted to Have High Binding
      Affinity to the Oncogenic Kinase PAK1: A Combined In Vitro and In Silico Study.
AB  - Sea cucumbers have long been utilized in foods and Asiatic folk medicines for
      their nutritive and health benefits. Herein, three sea cucumber species were
      investigated and Holothuria atra showed the highest cytotoxicity among these.
      Next, a desulfated saponin, desulfated echinoside B (DEB), was purified from H.
      atra through bioassay-guided fractionation. LC-ESI-MS (Liquid chromatography
      electrospray ionization mass spectrometry) analysis also showed H. atra to be a
      rich source of saponins. DEB showed cytotoxicity on cancer cells with IC50 values
      of 0.5-2.5 uM, and on brine shrimps with an IC50 value of 9.2 uM. In molecular
      docking studies, DEB was found to bind strongly with the catalytic domain of PAK1
      (p21-activated kinase 1) and it showed binding energy of -8.2 kcal/mol compared
      to binding energy of -7.7 kcal/mol for frondoside A (FRA). Both of them bind to
      the novel allosteric site close to the ATP-binding cleft. Molecular dynamics (MD)
      simulation demonstrated that DEB can form a more stable complex with PAK1,
      remaining inside the allosteric binding pocket and forming the maximum number of
      hydrogen bonds with the surrounding residues. Moreover, important ligand binding
      residues were found to be less fluctuating in the DEB-PAK1 complex than in the
      FRA-PAK1 complex throughout MD simulation. Our experimental and computational
      studies showed that both DEB and FRA can act as natural allosteric PAK1
      inhibitors and DEB appeared to be more promising than FRA.

PMID- 30200329
TI  - Evaluation of Hand-Dug Wells in Rural Haiti.
AB  - Water resources, especially safe, potable water, are limited for many Haitians.
      In areas where shallow groundwater is available, many household water needs such
      as laundry, bathing, and cooking are supplied by hand-dug wells. In order to
      better understand the water quality and prevalence of these household wells, 35
      hand-dug wells were surveyed and sampled near the Hopital Albert Schweitzer in
      Deschapelles, Haiti. Water samples were collected and tested for fecal coliform
      and Escherichia coli using the IDEXX Colilert-18 method. Of the samples
      collected, 89 percent were determined unsafe to use as a drinking water source
      based on the World Health Organization standard of 1.0 colony-forming unit (cfu)
      E. coli per 100 mL. Sixty-six percent of the wells exceeded recreational/body
      contact standards for the state of Michigan (130 cfu/100 mL). Some of these wells
      were deemed suitable for conversion to a new well type called in situ filtration
      (ISF) wells. In situ filtration wells are installed with an internal sand filter
      pack, PVC casing, pump, and cap which seals the well from surface contamination
      and provides additional water treatment as water is pumped. Previous ISF
      installations have reduced E. coli to safe drinking water levels within 90 days.

PMID- 30200331
TI  - Direct Asymmetric Reductive Amination for the Synthesis of (S)-Rivastigmine.
AB  - In this article we demonstrate how asymmetric total synthesis of (S)-rivastigmine
      has been achieved using direct asymmetric reductive amination as the key
      transformation in four steps. The route started with readily available and cheap
      m-hydroxyacetophenone, through esterification, asymmetric reductive amination, N
      diphenylmethyl deprotection and reductive amination, to provide the final (S)
      rivastigmine in 82% overall yield and 96% enantioselectivity. In the asymmetric
      reductive amination, catalysed by the iridium-phosphoramidite ligand complex and
      helped by some additives, the readily prepared 3-acetylphenyl
      ethyl(methyl)carbamate directly reductively coupled with diphenylmethanamine to
      yield the chiral amine product in 96% ee and 93% yield.

PMID- 30200332
TI  - Genetic Predisposition to Neuroblastoma.
AB  - Neuroblastoma is the most common solid tumor in children under the age of one. It
      displays remarkable phenotypic heterogeneity, resulting in differences in
      outcomes that correlate with clinical and biologic features at diagnosis. While
      neuroblastoma accounts for approximately 5% of all cancer diagnoses in
      pediatrics, it disproportionately results in about 9% of all childhood deaths.
      Research advances over the decades have led to an improved understanding of
      neuroblastoma biology. However, the initiating events that lead to the
      development of neuroblastoma remain to be fully elucidated. It has only been
      recently that advances in genetics and genomics have allowed researchers to
      unravel the predisposing factors enabling the development of neuroblastoma and
      fully appreciate the interplay between the genetics of tumor and host. In this
      review, we outline the current understanding of familial neuroblastoma and
      highlight germline variations that predispose children to sporadic disease. We
      also discuss promising future directions in neuroblastoma genomic research and
      potential clinical applications for these advances.

PMID- 30200335
TI  - Comparative Phytochemical Profiles and Antioxidant Enzyme Activity Analyses of
      the Southern Highbush Blueberry (Vaccinium corymbosum) at Different Developmental
      Stages.
AB  - In this study, the fruit quality, anthocyanin content and antioxidant enzyme
      activities of skin and pulp of southern blueberries (Vaccinium corymbosum) from
      China y at five developmental stages (green, pink, red, purple and blue) were
      investigated and anthocyanins were characterized and quantified by HPLC during
      the considered developmental stages. The results indicatated that the contents of
      phenolic, flavonoids and anthocyanin as well as antioxidant enzyme activities
      varied depending on the developmental stages. The correlation values between
      total phenolic content (TPC), total flavonoids content (TFC) and total
      anthocyanin content (TAC) were significant. The highest activity of peroxidase
      (POD) and catalase (CAT) was found in red fruit, and the variety of monomeric
      anthocyanin increased gradually, skin from blue fruit possessed higher TAC.
      However, the highest activity of polyphenol oxidase (PPO) and superoxide
      dismutase (SOD) were detected in green and blue fruit, respectively. In the
      present work, the differences regarding phytochemical profiles and antioxidant
      enzyme activities were mainly correlated with developmental stages of fruit.

PMID- 30200333
TI  - Machine Learning for Drug-Target Interaction Prediction.
AB  - Identifying drug-target interactions will greatly narrow down the scope of search
      of candidate medications, and thus can serve as the vital first step in drug
      discovery. Considering that in vitro experiments are extremely costly and time
      consuming, high efficiency computational prediction methods could serve as
      promising strategies for drug-target interaction (DTI) prediction. In this
      review, our goal is to focus on machine learning approaches and provide a
      comprehensive overview. First, we summarize a brief list of databases frequently
      used in drug discovery. Next, we adopt a hierarchical classification scheme and
      introduce several representative methods of each category, especially the recent
      state-of-the-art methods. In addition, we compare the advantages and limitations
      of methods in each category. Lastly, we discuss the remaining challenges and
      future outlook of machine learning in DTI prediction. This article may provide a
      reference and tutorial insights on machine learning-based DTI prediction for
      future researchers.

PMID- 30200334
TI  - The Energetic Viability of Delta1-Piperideine Dimerization in Lysine-derived
      Alkaloid Biosynthesis.
AB  - Lys-derived alkaloids widely distributed in plant kingdom have received
      considerable attention and have been intensively studied; however, little is
      known about their biosynthetic mechanisms. In terms of the skeleton formation,
      for example, of quinolizidine alkaloid biosynthesis, only the very first two
      steps have been identified and the later steps remain unknown. In addition, there
      is no available information on the number of enzymes and reactions required for
      their skeletal construction. The involvement of the Delta 1 -piperideine
      dimerization has been proposed for some of the Lys-derived alkaloid biosyntheses,
      but no enzymes for this dimerization reaction have been reported to date;
      moreover, it is not clear whether this dimerization reaction proceeds
      spontaneously or enzymatically. In this study, the energetic viability of the
      Delta 1 -piperideine dimerizations under neutral and acidic conditions was
      assessed using the density functional theory computations. In addition, a similar
      type of reaction in the dipiperidine indole alkaloid, nitramidine, biosynthesis
      was also investigated. Our findings will be useful to narrow down the candidate
      genes involved in the Lys-derived alkaloid biosynthesis.

PMID- 30200337
TI  - A Novel Metamaterial Inspired High-Temperature Microwave Sensor in Harsh
      Environments.
AB  - A high-temperature sensor based on a metamaterial unit cell is proposed in this
      paper. The wireless passive temperature sensing method is based on the
      electromagnetic backscatter principle, and thus has the advantages of higher
      quality, lower environmental interference, and anti-low frequency interference.
      We developed a finite-element method-based model for the sensor via high
      frequency simulation software (HFSS). A double split-ring resonator (SRR) with an
      outer ring length of 13 mm was designed on alumina ceramic substrate. The sensor
      was fabricated at 2.42 GHz using micromechanical technology and screen printing
      technology. When the temperature increased from 28 to 1100  degrees C, the
      resonant frequency decreased from 2.417 to 2.320 GHz with an average sensitivity
      of 95.63 kHz/ degrees C. As the sensor is easily designed and fabricated, it can
      be used for chipless radio frequency identification (RFID) tags by simply
      changing the size of rings. Furthermore, emerging 3D printing technology and
      commercial desktop inkjet printers will be used to realize the rapid low-cost
      preparation of the sensor, enabling its wide range of applications in aerospace,
      military, manufacturing, transportation, and other fields.

PMID- 30200336
TI  - Oxygen-Carrying Micro/Nanobubbles: Composition, Synthesis Techniques and
      Potential Prospects in Photo-Triggered Theranostics.
AB  - Microbubbles and nanobubbles (MNBs) can be prepared using various shells, such as
      phospholipids, polymers, proteins, and surfactants. MNBs contain gas cores due to
      which they are echogenic and can be used as contrast agents for ultrasonic and
      photoacoustic imaging. These bubbles can be engineered in various sizes as
      vehicles for gas and drug delivery applications with novel properties and
      flexible structures. Hypoxic areas in tumors develop owing to an imbalance of
      oxygen supply and demand. In tumors, hypoxic regions have shown more resistance
      to chemotherapy, radiotherapy, and photodynamic therapies. The efficacy of
      photodynamic therapy depends on the effective accumulation of photosensitizer
      drug in tumors and the availability of oxygen in the tumor to generate reactive
      oxygen species. MNBs have been shown to reverse hypoxic conditions, degradation
      of hypoxia inducible factor 1alpha protein, and increase tissue oxygen levels.
      This review summarizes the synthesis methods and shell compositions of
      micro/nanobubbles and methods deployed for oxygen delivery. Methods of
      functionalization of MNBs, their ability to deliver oxygen and drugs,
      incorporation of photosensitizers and potential application of photo-triggered
      theranostics, have also been discussed.

PMID- 30200338
TI  - Screening of Cytotoxicity and Anti-Inflammatory Properties of Feijoa Extracts
      Using Genetically Modified Cell Models Targeting TLR2, TLR4 and NOD2 Pathways,
      and the Implication for Inflammatory Bowel Disease.
AB  - Feijoa has been increasingly studied in the recent decade, while investigations
      into its bioactivities including anti-inflammatory activity are lacking. In this
      article, the cytotoxicity and anti-inflammatory properties of feijoa extracts,
      from flesh, peel and whole fruit, from four cultivars namely APOLLO, UNIQUE, OPAL
      STAR and WIKI TU are presented. Three inflammatory pathways, Toll-like receptor 2
      (TLR2), TLR4 and nucleotide-binding oligomerization domain-containing protein 2
      (NOD2), were investigated using genetically modified cell models namely HEK
      BlueTM hTLR2, HEK-BlueTM hTLR4, NOD2-WT and NOD2-G908R. Results show that feijoa
      peel extract induced higher cytotoxicity than flesh and whole fruit extracts, and
      the APOLLO cultivar was the most anti-inflammatory among the four tested
      cultivars. The anti-inflammatory activity of feijoa flesh was detected only
      through the TLR2 pathway, and the activity of feijoa peel and whole fruit was
      evident mainly through the TLR2 and NOD2 pathways. Most notably, feijoa anti
      inflammatory activity was superior to ibuprofen particularly through the TLR2
      pathway, with significantly lower secreted embryonic alkaline phosphatase IC50
      concentrations (7.88, 12.81, 30.84 and 442.90 MUg/mL for APOLLO flesh, peel,
      whole fruit extract and ibuprofen respectively). These findings indicate that
      feijoa has great potential to be used in the treatment and prevention of
      inflammation-related diseases including inflammatory bowel disease.

PMID- 30200339
TI  - A Novel Dielectric Tomography System for In-Situ Tracking Three-Dimensional Soil
      Water Dynamics.
AB  - In this study, we developed a novel dielectric tomography system for in-situ
      tracking three-dimensional (3D) soil water dynamics. The system was designed to
      control a single dielectric tube sensor that automatically lowered in a PVC tube
      array installed in-situ to determine the water content of a soil profile, which
      eliminated probe-to-probe uncertainties and labor costs. Two tests for evaluating
      the novel system were conducted (i) to analyze and correct the positional error
      of the probe due to out-of-step errors of stepper motors, and (ii) to track and
      visualize 3D soil water temporal variations in a soil tank with heterogenetic
      bulk densities and initial water contents under drip irrigation. The results show
      that the positioning correcting algorithm combined with starting point alignment
      can minimize the positioning error of the probe during the 3D tomography. The
      single drip emitter test illustrated spatial and temporal variations of soil
      water content due to heterogeneous soil properties in vertical and horizontal
      directions around the access tube array. Based on these data, 3D distributions of
      soil water dynamics were visualized. The developed tomography system has
      potential application to be extended to the local scale in a greenhouse or the
      large scale in an agricultural field. Future research should explore the
      performance for agricultural crop irrigation or for modeling and validating soil
      water flow or hydrological process under either steady state or non-steady state
      condition.

PMID- 30200341
TI  - Equivalent Circuit Modeling for a Valveless Piezoelectric Pump.
AB  - Various kinds of the models had been proposed to explain the relationship between
      the performance and the structural parameters of valveless piezoelectric pumps,
      so as to evaluate the functional performance such devices. Among the models, the
      equivalent circuit model, which converts the multi-field problem of a valveless
      piezoelectric pump system into a simple circuit problem, is the most simple and
      clear one. Therefore, the proposed structure and working principle of the
      valveless piezoelectric pump with multistage Y-shape treelike bifurcate tubes are
      analyzed; then, the equivalent circuit model of the valveless piezoelectric pump
      is established based on the working principles of this pump and liquid-electric
      analogy theory. Finally, an experimental study of the pump is carried out, with a
      comparative analysis of the experimental results and the simulation results of
      the generated equivalent circuit. The experimental results show that with a
      driving voltage of 100 V and frequency of 6 Hz, the maximum flow rate of the
      valveless piezoelectric pump is 1.16 mL/min. Meanwhile, the output current of
      equivalent circuit also reaches its peak at the frequency of 6 Hz, therefore,
      indicating a good predictive ability of this model in calculating the maximum
      output flow rate and best working frequency of valveless piezoelectric pumps.

PMID- 30200340
TI  - Residue Depletion of Florfenicol and Florfenicol Amine in Broiler Chicken Claws
      and a Comparison of Their Concentrations in Edible Tissues Using LC-MS/MS.
AB  - Antimicrobial residues might persist in products and by-products destined for
      human or animal consumption. Studies exploring the depletion behavior of
      florfenicol residues in broiler chicken claws are scarce, even though claws can
      enter the food chain directly or indirectly. Hence, this study intended to assess
      the concentrations of florfenicol (FF) and florfenicol amine (FFA)-its active
      metabolite-in chicken claws from birds that were treated with a therapeutic dose
      of florfenicol. Furthermore, concentrations of these analytes in this matrix were
      compared with their concentrations in edible tissues at each sampling point. A
      group of 70 broiler chickens were raised under controlled conditions and used to
      assess residue depletion. Sampling points were on days 5, 10, 20, 25, 30, 35, and
      40 after ceasing treatment, thus extending beyond the withdrawal period
      established for muscle tissue (30 days). Analytes were extracted using HPLC-grade
      water and acetone, and dichloromethane was used for the clean-up stage. Liquid
      chromatography coupled to mass spectroscopy detection (LC-MS/MS) was used to
      detect and quantify the analytes. The analytical methodology developed in this
      study was validated in-house and based on the recommendations described in the
      Commission Decision 2002/657/EC from the European Union. Analyte concentrations
      were calculated by linear regression analysis of calibration curves that were
      fortified using an internal standard of chloramphenicol-d5 (CAF-d5). The
      depletion time of FF and FFA was set at 74 days in claws, based on a 95%
      confidence level and using the limit of detection (LOD) as the cut-off point. Our
      findings show that FF and FFA can be found in chicken claws at higher
      concentrations than in muscle and liver samples at each sampling point.

PMID- 30200342
TI  - Ni-Doped ZnS Nanospheres Decorated with Au Nanoparticles for Highly Improved Gas
      Sensor Performance.
AB  - Novel Ni-doped wurtzite ZnS nanospheres decorated with Au nanoparticles (Au NPs
      ZnS NSs) have been successfully fabricated using a simple method involving vacuum
      evaporation followed by an annealing process. This transition metal-doped gas
      sensor had high responsivity, extremely fast response and recovery time, and
      excellent selectivity to formaldehyde at room temperature. The response and
      recovery time are only 29 s and 2 s, respectively. Since ZnS is transformed into
      ZnO at a high temperature, superior room temperature-sensing performance can
      improve the stability and service life of the sensor. The improvement in sensing
      performance could be attributed to the reduced charge-transfer distance resulting
      from the creation of a local charge reservoir layer, and the catalytic and
      spillover effect of Au nanoparticles. The rough and porous spherical structure
      can also facilitate the detection and diffusion of gases. The as-prepared Au NPs
      ZnS NSs are considered to be an extremely promising candidate material for gas
      sensors, and are expected to have other potential applications in the future.

PMID- 30200343
TI  - Development of Colorimetric and Ratiometric Fluorescence Membranes for Detection
      of Nitrate in the Presence of Aluminum-Containing Compounds.
AB  - In this study, a quantitative analysis of nitrate in aqueous solution was
      performed through the combination of an oxazine170 perchlorate-ethyl cellulose
      (O17-EC) membrane with aluminum-containing compounds. Aluminum of Devarda's alloy
      (DA) or a clay hydrotalcite (HT) was employed for the reduction of nitrate to
      produce ammonia, and the produced ammonia was detected by the O17-EC membrane.
      The method of combining the O17-EC membrane with aluminum compounds has showed a
      broad detection range of nitrate. That is, the DA was combined with the O17-EC
      membrane and showed the linear nitrate detection ranges of 1-10 mM and 10-100 mM,
      while the O17-EC membrane immobilized with the clay HT showed a linear detection
      range of 0.1-1 mM nitrate. The visual color transition of the nitrate-sensing
      membranes at different nitrate concentrations was clearly observed under sunlight
      or irradiation of a light-emitting diode (LED) at an excitation wavelength of 470
      nm (LED470).

PMID- 30200344
TI  - Molecular Pathways of Estrogen Receptor Action.

PMID- 30200345
TI  - Recombinant Escherichia coli BL21-pET28a-egfp Cultivated with Nanomaterials in a
      Modified Microchannel for Biofilm Formation.
AB  - The application of whole cells as catalytic biofilms in microchannels has
      attracted increasing scientific interest. However, the excessive biomass
      formation and structure of biofilms in a reactor limits their use. A microchannel
      reactor with surface modification was used to colonize recombinant Escherichia
      coil BL21-pET28a-egfp rapidly and accelerated growth of biofilms in the
      microchannel. The segmented flow system of 'air/culture medium containing
      nanomaterials' was firstly used to modulate the biofilms formation of recombinant
      E. coil; the inhibitory effects of nanomaterials on biofilm formation were
      investigated. The results indicated that the segmental flow mode has a
      significant impact on the structure and development of biofilms. Using the
      channels modified by silane reagent, the culture time of biofilms (30 h) was
      reduced by 6 h compared to unmodified channels. With the addition of graphene
      sheets (10 mg/L) in Luria-Bertani (LB) medium, the graphene sheets possessed a
      minimum inhibition rate of 3.23% against recombinant E. coil. The biofilms
      cultivated by the LB medium with added graphene sheets were stably formed in 20
      h; the formation time was 33.33% shorter than that by LB medium without graphene.
      The developed method provides an efficient and simple approach for rapid
      preparation of catalytic biofilms in microchannel reactors.

PMID- 30200346
TI  - Tracing the Thermal History of Seafood Products through Lysophospholipid Analysis
      by Hydrophilic Interaction Liquid Chromatography-Electrospray Ionization Fourier
      Transform Mass Spectrometry.
AB  - Low temperature treatments commonly applied to seafood products have been shown
      to influence their phospholipid (PL) profile through enzymatic hydrolysis. In the
      present study, the generation of lysophospholipids (LPL) resulting from this
      process was systematically investigated for selected, commercially relevant
      seafood products, namely oysters, clams, octopuses, and shrimps. These products
      were subjected to thermal treatments like refrigeration or freezing after being
      purchased as fresh, defrozen, or frozen products depending on the case. The
      coupling between hydrophilic interaction liquid chromatography (HILIC) and
      electrospray ionization with high resolution/accuracy Fourier transform mass
      spectrometry (ESI-FTMS) was exploited to evaluate the PL profile of the cited
      products, especially the incidence of LPL related to the two main PL classes of
      seafood products-phosphatidylcholines (PC) and phosphatidylethanolamines (PE)-in
      the lipid extracts. The lyso forms of PE (LPE) were found to be generally more
      sensitive than those of PC (LPC) to thermal treatments, usually exhibiting a
      significant increase upon prolonged refrigeration at 4  degrees C in all types of
      investigated products except European flat oysters. Moreover, the distinction
      between fresh and frozen or defrozen products could be achieved in the case of
      octopuses and shrimps, respectively.

PMID- 30200347
TI  - An Energy Conserving and Transmission Radius Adaptive Scheme to Optimize
      Performance of Energy Harvesting Sensor Networks.
AB  - In energy harvesting wireless sensor networks (EHWSNs), the energy tension of the
      network can be relieved by obtaining the energy from the surrounding environment,
      but the cost on hardware cannot be ignored. Therefore, how to minimize the cost
      of energy harvesting hardware to reduce the network deployment cost, and further
      optimize the network performance, is still a challenging issue in EHWSNs. In this
      paper, an energy conserving and transmission radius adaptive (ECTRA) scheme is
      proposed to reduce the cost and optimize the performance of solar-based EHWSNs.
      There are two main innovations of the ECTRA scheme. Firstly, an energy conserving
      approach is proposed to conserve energy and avoid outage for the nodes in
      hotspots, which are the bottleneck of the whole network. The novelty of this
      scheme is adaptively rotating the transmission radius. In this way, the nodes
      with maximum energy consumption are rotated, balancing energy consumption between
      nodes and reducing the maximum energy consumption in the network. Therefore, the
      battery storage capacity of nodes and the cost on hardware. Secondly, the ECTRA
      scheme selects a larger transmission radius for rotation when the node can absorb
      enough energy from the surroundings. The advantages of using this method are: (a)
      reducing the energy consumption of nodes in near-sink areas, thereby reducing the
      maximum energy consumption and allowing the node of the hotspot area to conserve
      energy, in order to prevent the node from outage. Hence, the network deployment
      costs can be further reduced; (b) reducing the network delay. When a larger
      transmission radius is used to transmit data in the network, fewer hops are
      needed by data packet to the sink. After the theoretical analyses, the results
      show the following advantages compared with traditional method. Firstly, the
      ECTRA scheme can effectively reduce deployment costs by 29.58% without effecting
      the network performance as shown in experiment analysis; Secondly, the ECTRA
      scheme can effectively reduce network data transmission delay by 44-71%; Thirdly,
      the ECTRA scheme shows a better balance in energy consumption and the maximum
      energy consumption is reduced by 27.89%; And lastly, the energy utilization rate
      is effectively improved by 30.09-55.48%.

PMID- 30200348
TI  - Kernel Sparse Representation with Hybrid Regularization for On-Road Traffic
      Sensor Data Imputation.
AB  - The problem of missing values (MVs) in traffic sensor data analysis is universal
      in current intelligent transportation systems because of various reasons, such as
      sensor malfunction, transmission failure, etc. Accurate imputation of MVs is the
      foundation of subsequent data analysis tasks since most analysis algorithms need
      complete data as input. In this work, a novel MVs imputation approach termed as
      kernel sparse representation with elastic net regularization (KSR-EN) is
      developed for reconstructing MVs to facilitate analysis with traffic sensor data.
      The idea is to represent each sample as a linear combination of other samples due
      to inherent spatiotemporal correlation, as well as periodicity of daily traffic
      flow. To discover few yet correlated samples and make full use of the valuable
      information, a combination of l1-norm and l2-norm is employed to penalize the
      combination coefficients. Moreover, the linear representation among samples is
      extended to nonlinear representation by mapping input data space into high
      dimensional feature space, which further enhances the recovery performance of our
      proposed approach. An efficient iterative algorithm is developed for solving KSR
      EN model. The proposed method is verified on both an artificially simulated
      dataset and a public road network traffic sensor data. The results demonstrate
      the effectiveness of the proposed approach in terms of MVs imputation.

PMID- 30200349
TI  - Rapid Population Growth throughout Asia's Earthquake-Prone Areas: A Multiscale
      Analysis.
AB  - Assessing the changes of the population living throughout the most seismically
      hazardous area (MSHA) constitutes an important foundation for seismic risk
      assessment. However, the changes of the population living in the MSHA of Asia,
      which exhibits the highest number of earthquake related fatalities, were poorly
      understood. Therefore, this study analyzed the changes of the population in the
      MSHA between 2000 and 2015 at the continental, subcontinental, and national
      scales. We found that the population, especially the vulnerable population (i.e.,
      children under or equal to the age of 14 and elderly people over or equal to the
      age of 65), in Asia's MSHA increased rapidly between 2000 and 2015. The
      population in the MSHA increased by 185.88 million with a growth rate of 20.93%,
      which was 3.38% greater than that in the non-MSHA region. Meanwhile, the
      vulnerable population in the MSHA increased by 63.65 million with a growth rate
      of 19.73%. The increase of the vulnerable population in the MSHA was 19.93%
      greater than that in the non-MSHA region. We also found that urban population
      growth was a major factor impacting the increase in both the population and the
      vulnerable population throughout Asia's MSHA. Therefore, attention should be paid
      to the changes of the population in Asia's MSHA, whilst it is imperative to
      execute strict building codes and select the development location more carefully
      in the MSHA.

PMID- 30200350
TI  - Assessing Metagenomic Signals Recovered from Lyuba, a 42,000-Year-Old Permafrost
      Preserved Woolly Mammoth Calf.
AB  - The reconstruction of ancient metagenomes from archaeological material, and their
      implication in human health and evolution, is one of the most recent advances in
      paleomicrobiological studies. However, as for all ancient DNA (aDNA) studies,
      environmental and laboratory contamination need to be specifically addressed.
      Here we attempted to reconstruct the tissue-specific metagenomes of a 42,000-year
      old, permafrost-preserved woolly mammoth calf through shotgun high-throughput
      sequencing. We analyzed the taxonomic composition of all tissue samples together
      with environmental and non-template experimental controls and compared them to
      metagenomes obtained from permafrost and elephant fecal samples. Preliminary
      results suggested the presence of tissue-specific metagenomic signals. We
      identified bacterial species that were present in only one experimental sample,
      absent from controls, and consistent with the nature of the samples. However, we
      failed to further authenticate any of these signals and conclude that, even when
      experimental samples are distinct from environmental and laboratory controls,
      this does not necessarily indicate endogenous presence of ancient host-associated
      microbiomic signals.

PMID- 30200352
TI  - A Robust Terrain Aided Navigation Using the Rao-Blackwellized Particle Filter
      Trained by Long Short-Term Memory Networks.
AB  - Terrain-aided navigation (TAN) is a technology that estimates the position of the
      vehicle by comparing the altitude measured by an altimeter and height from the
      digital elevation model (DEM). The particle filter (PF)-based TAN has been
      commonly used to obtain stable real-time navigation solutions in cases where the
      unmanned aerial vehicle (UAV) operates at a high altitude. Even though TAN
      performs well on rough and unique terrains, its performance degrades in flat and
      repetitive terrains. In particular, in the case of PF-based TAN, there has been
      no verified technique for deciding its terrain validity. Therefore, this study
      designed a Rao-Blackwellized PF (RBPF)-based TAN, used long short-term memory
      (LSTM) networks to endure flat and repetitive terrains, and trained the noise
      covariances and measurement model of RBPF. LSTM is a modified recurrent neural
      network (RNN), which is an artificial neural network that recognizes patterns
      from time series data. Using this, this study tuned the noise covariances and
      measurement model of RBPF to minimize the navigation errors in various flight
      trajectories. This paper designed a TAN algorithm based on combining RBPF and
      LSTM and confirmed that it can enable a more precise navigation performance than
      conventional RBPF based TAN through simulations.

PMID- 30200351
TI  - The Healing Effect of Human Milk Fat Globule-EGF Factor 8 Protein (MFG-E8) in A
      Rat Model of Parkinson's Disease.
AB  - We searched for drugs that alleviate the reduction of dopaminergic neurons caused
      by the administration of lipopolysaccharide (LPS) to the substantia nigra of the
      rat brain. Human milk fat globule-EGF factor 8 protein (MFG-E8) is similar to MFG
      E8-S, a short isoform, of the mouse MFG-E8. However, the function of MFG-E8-S was
      not clear. Rats with LPS-induced Parkinson's disease were prepared and the
      effects of human MFG-E8 were examined. MFG-E8 improved the significant reduction
      in mesencephalic dopamine neurons induced by the administration of LPS. LPS was
      administered to human induced pluripotent stem cell (iPSC)-derived dopaminergic
      neurons to induce inflammation and the effect of MFG-E8 was examined. MFG-E8
      showed no toxicity toward neurons. We reanalyzed the results using public
      microarray data. MFG-E8 mRNA was found to be expressed in all parts of the body,
      particularly by adipose-derived stem cells (ADSCs). Furthermore, we investigated
      the culture supernatant of ADSCs using the liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) analysis method and successfully identified the peptide
      of the MFG-E8 F5/8 type C domain. The results suggested that MFG-E8-S may have a
      preventive effect against Parkinson's disease.

PMID- 30200353
TI  - A High-Efficiency Data Collection Method Based on Maximum Recharging Benefit in
      Sensor Networks.
AB  - To reduce time delays during data collection and prolong the network lifetime in
      Wireless Rechargeable Sensor Networks (WRSNs), a type of high-efficiency data
      collection method based on Maximum Recharging Benefit (DCMRB) is proposed in this
      paper. According to the minimum number of the Mobile Data Collectors (MDCs), the
      network is firstly divided into several regions with the help of the Virtual Scan
      Line (VSL). Then, the MDCs and the Wireless Charging Vehicles (WCVs) are employed
      in each region for high efficient data collection and energy replenishment. In
      order to ensure the integrity of data collection and reduce the rate of packet
      loss, a speed adjustment scheme for MDC is also proposed. In addition, by
      calculating the adaptive threshold of the recharging request, those nodes with
      different energy consumption rates are recharged in a timely way that avoids
      their premature death. Finally, the limited battery capacity of WCVs and their
      energy consumption while moving are also taken into account, and an adaptive
      recharging scheme based on maximum benefit is proposed. Experimental results show
      that the energy consumption is effectively balanced in DCMRB. Furthermore, this
      can not only enhance the efficiency of data collection, but also prolong the
      network lifetime compared with the Energy Starvation Avoidance Online Charging
      scheme (ESAOC), Greedy Mobile Scheme based on Maximum Recharging Benefit (GMS
      MRB) and First-Come First-Served (FCFS) methods.

PMID- 30200354
TI  - Surface Sizing Treated MWCNTs and Its Effect on the Wettability, Interfacial
      Interaction and Flexural Properties of MWCNT/Epoxy Nanocomposites.
AB  - A surface-sizing technique was offered to take full advantage of multi-walled
      carbon nanotubes (MWCNTs) and epoxy resins. Two surface-sizing treated MWCNTs
      were obtained through a ball-milling treatment of amino-functionalized MWCNTs
      (MWCNT-NH2) with n-butyl glycidylether (BuGE) and benzyl glycidylether (BeGE).
      These were referred to as MWCNT-BuGE and MWCNT-BeGE. The results indicated that
      the surface sizing effectively enhanced wettability, dispersibility of MWCNTs in
      the epoxy resin. These ameliorating effects, along with improved interfacial
      interaction between MWCNT-BeGE containing benzene rings and the epoxy matrix,
      which can offer a more efficient local load-transfer from matrix to MWCNTs, as
      observed by a higher G-band shift in Raman spectrum under bending loads than that
      of MWCNT-BuGE reinforced ones. Correspondingly, MWCNT-BeGE/epoxy nanocomposites
      exhibited increasing flexural strength and modulus of 22.9% and 37.8%
      respectively compared with the neat epoxy, and 7.3% and 7.7% respectively
      compared with MWCNT-BuGE/epoxy nanocomposites with the same MWCNT content.

PMID- 30200355
TI  - Protein Targets of Frankincense: A Reverse Docking Analysis of Terpenoids from
      Boswellia Oleo-Gum Resins.
AB  - Background: Frankincense, the oleo-gum resin of Boswellia trees, has been used in
      traditional medicine since ancient times. Frankincense has been used to treat
      wounds and skin infections, inflammatory diseases, dementia, and various other
      conditions. However, in many cases, the biomolecular targets for frankincense
      components are not well established. Methods: In this work, we have carried out a
      reverse docking study of Boswellia diterpenoids and triterpenoids with a library
      of 16034 potential druggable target proteins. Results:Boswellia diterpenoids
      showed selective docking to acetylcholinesterase, several bacterial target
      proteins, and HIV-1 reverse transcriptase. Boswellia triterpenoids targeted the
      cancer-relevant proteins (poly(ADP-ribose) polymerase-1, tankyrase, and folate
      receptor beta), inflammation-relevant proteins (phospholipase A2, epoxide
      hydrolase, and fibroblast collagenase), and the diabetes target 11beta
      hydroxysteroid dehydrogenase. Conclusions: The preferential docking of Boswellia
      terpenoids is consistent with the traditional uses and the established biological
      activities of frankincense.

PMID- 30200356
TI  - Spatial Patterns of Urban Wastewater Discharge and Treatment Plants Efficiency in
      China.
AB  - With the rapid economic development, water pollution has become a major concern
      in China. Understanding the spatial variation of urban wastewater discharge and
      measuring the efficiency of wastewater treatment plants are prerequisites for
      rationally designing schemes and infrastructures to control water pollution.
      Based on the input and output urban wastewater treatment data of the 31 provinces
      of mainland China for the period 2011-2015, the spatial variation of urban water
      pollution and the efficiency of wastewater treatment plants were measured and
      mapped. The exploratory spatial data analysis (ESDA) model and super-efficiency
      data envelopment analysis (DEA) combined Malmquist index were used to achieve
      this goal. The following insight was obtained from the results. (1) The intensity
      of urban wastewater discharge increased, and the urban wastewater discharge
      showed a spatial agglomeration trend for the period 2011 to 2015. (2) The average
      inefficiency of wastewater treatment plants (WWTPs) for the study period was
      39.2%. The plants' efficiencies worsened from the eastern to western parts of the
      country. (3) The main reasons for the low efficiency were the lack of
      technological upgrade and scale-up. The technological upgrade rate was -4.8%,
      while the scale efficiency increases as a result of scaling up was -0.2%.
      Therefore, to improve the wastewater treatment efficiency of the country, the
      provinces should work together to increase capital investment and technological
      advancement.

PMID- 30200357
TI  - The Combined Process of Paper Filtration and Ultrafiltration for the Pretreatment
      of the Biogas Slurry from Swine Manure.
AB  - The membrane process had been applied for the advanced treatment of pig farm
      biogas slurry. As studied, this physical pretreatment, with low cost and high
      efficiency of the suspended solids removal and nutrient retention, is required to
      control membrane fouling. The combined process of paper filtration and
      ultrafiltration in a pilot scale was applied in the present study. The main
      objective was to explore and identify the feasibility of the new process for the
      pretreatment of the separation liquid of pig farm biogas slurry. A precision
      identification experiment of paper filtration and the multi-batch repetitive
      experiments of the combined process were designed. The results showed, at the
      identified paper filtration precision of 50MUm and an operating pressure of 0.3
      bar of the ultrafiltration process, that the flux rate at the stable stage of the
      multi-batch operation was around 295.00 L/h. The combined process achieved an
      overall processing rate of 345.41 +/- 18.81 L/h and a volume permeation
      proportion of 82.45% +/- 0.85%. The TSS was removed by 95.71%, but total nitrogen
      (TN) and ammonia nitrogen (NH3-N) were retained by 76.29% +/- 2.04% and 73.74% +/
      2.10%, respectively. Comprehensively, the requirement for the pretreatment was
      obtained.

PMID- 30200359
TI  - Chemical Fingerprinting and Quantification of Chinese Cinnamomi Cortex by Ultra
      High Performance Liquid Chromatography Coupled with Chemometrics Methods.
AB  - To rapidly clarify and quantify the chemical profiling of Cinnamomi cortex a
      reliable and feasible strategy of chromatographic fingerprinting with a suite of
      chemometrics methods was developed and validated by ultra-high performance liquid
      chromatography coupled with diode array detection. Furthermore, to identify more
      meaningful chemical markers, the chemometrics methods including hierarchical
      cluster analysis (HCA), principal component analysis (PCA) and similarity, which
      all generate quality evaluations and correlation classifications of Cinnamomi
      cortex, were used to improve the Cinnamomi cortex quality control standards. A
      total of 12 characteristic peaks were confirmed, seven of which were identified
      by comparing their retention times, UV and MS spectra with authentic compounds.
      Moreover, 11 analytes were accurately determined, as a complementary
      quantification method of chromatographic fingerprinting. For quantitative
      analyses, selective detection was performed at 254, 280 and 340 nm. The tested
      samples were separated and determined using UPLC and a series of methodologies
      including linearity, precision, accuracy, limit of detection and quantification
      and extraction recoveries were validated. Meanwhile the method bias for all the
      analytes did not exceed 5%. A total of 42 samples were acquired in China and
      analyzed. The results demonstrated that chromatographic fingerprinting in
      combination with chemometrics methods provides a promising and practical method
      to more effectively and comprehensively control the quality of Cinnamomi cortex
      from various sources, which would be a useful reference for the development and
      further study of Cinnamomi cortex and related formulations.

PMID- 30200361
TI  - A Novel Substance P-Based Hydrogel for Increased Wound Healing Efficiency.
AB  - The neuropeptide substance P (SP) is known to stimulate wound healing by
      regulating the production of relevant cytokines as well as cell proliferation and
      migration. However, the therapeutic application of SP is limited by its low
      stability under biological conditions and oxidation during purification,
      formulation, and storage. To address this problem, we developed a novel
      formulation of SP as an SP gel, and investigated its wound healing activity both
      in vitro and in vivo. SP in SP gel was stable at various temperatures for up to 4
      weeks. In vitro, SP gel exhibited more potential as a candidate wound-healing
      agent than SP alone, as evidenced by the observed increases in the proliferation
      and migration of human epidermal keratinocytes and human dermal fibroblasts. In
      vivo experiments showed that SP gel treatment enhanced the healing of full
      thickness wounds in mice as compared to SP alone. These results demonstrate the
      benefits of SP gel as a promising topical agent for wound treatment.

PMID- 30200360
TI  - Network-Based Approaches to Explore Complex Biological Systems towards Network
      Medicine.
AB  - Network medicine relies on different types of networks: from the molecular level
      of protein-protein interactions to gene regulatory network and correlation
      studies of gene expression. Among network approaches based on the analysis of the
      topological properties of protein-protein interaction (PPI) networks, we discuss
      the widespread DIAMOnD (disease module detection) algorithm. Starting from the
      assumption that PPI networks can be viewed as maps where diseases can be
      identified with localized perturbation within a specific neighborhood (i.e.,
      disease modules), DIAMOnD performs a systematic analysis of the human PPI network
      to uncover new disease-associated genes by exploiting the connectivity
      significance instead of connection density. The past few years have witnessed the
      increasing interest in understanding the molecular mechanism of post
      transcriptional regulation with a special emphasis on non-coding RNAs since they
      are emerging as key regulators of many cellular processes in both physiological
      and pathological states. Recent findings show that coding genes are not the only
      targets that microRNAs interact with. In fact, there is a pool of different RNAs
      including long non-coding RNAs (lncRNAs) -competing with each other to attract
      microRNAs for interactions, thus acting as competing endogenous RNAs (ceRNAs).
      The framework of regulatory networks provides a powerful tool to gather new
      insights into ceRNA regulatory mechanisms. Here, we describe a data-driven model
      recently developed to explore the lncRNA-associated ceRNA activity in breast
      invasive carcinoma. On the other hand, a very promising example of the co
      expression network is the one implemented by the software SWIM (switch miner),
      which combines topological properties of correlation networks with gene
      expression data in order to identify a small pool of genes-called switch genes
      critically associated with drastic changes in cell phenotype. Here, we describe
      SWIM tool along with its applications to cancer research and compare its
      predictions with DIAMOnD disease genes.

PMID- 30200362
TI  - Five-Golden-Flowers Tea: Green Extraction and Hepatoprotective Effect against
      Oxidative Damage.
AB  - The consumption of herbal teas has become popular in recent years due to their
      attractive flavors and outstanding antioxidant properties. The Five-Golden
      Flowers tea is a herbal tea consisting of five famous edible flowers. The effects
      of microwave-assisted extraction parameters on the antioxidant activity of Five
      Golden-Flowers tea were studied by single-factor experiments, and further
      investigated using response surface methodology. Under the optimal parameters
      (53.04 mL/g of solvent/material ratio, 65.52  degrees C, 30.89 min, and 500 W),
      the ferric-reducing antioxidant power, Trolox equivalent antioxidant capacity,
      and total phenolic content of the herbal tea were 862.90 +/- 2.44 umol Fe2+/g dry
      weight (DW), 474.37 +/- 1.92 umol Trolox/g DW, and 65.50 +/- 1.26 mg gallic acid
      equivalent (GAE)/g DW, respectively. The in vivo antioxidant activity of the
      herbal tea was evaluated on alcohol-induced acute liver injury in mice. The
      herbal tea significantly decreased the levels of aspartate aminotransferase,
      total bilirubin, and malonaldehyde at different doses (200, 400, and 800 mg/kg);
      improved the levels of liver index, serum triacylglycerol, and catalase at dose
      of 800 mg/kg. These results indicated its role in alleviating hepatic oxidative
      injury. Besides, rutin, chlorogenic acid, epicatechin, gallic acid, and p
      coumaric acid were identified and quantified by high performance liquid
      chromatography (HPLC), which could contribute to the antioxidant activity of the
      herbal tea.

PMID- 30200358
TI  - NMR as a Tool to Investigate the Processes of Mitochondrial and Cytosolic Iron
      Sulfur Cluster Biosynthesis.
AB  - Iron-sulfur (Fe-S) clusters, the ubiquitous protein cofactors found in all
      kingdoms of life, perform a myriad of functions including nitrogen fixation,
      ribosome assembly, DNA repair, mitochondrial respiration, and metabolite
      catabolism. The biogenesis of Fe-S clusters is a multi-step process that involves
      the participation of many protein partners. Recent biophysical studies, involving
      X-ray crystallography, nuclear magnetic resonance (NMR) spectroscopy, mass
      spectrometry (MS), and small angle X-ray scattering (SAXS), have greatly improved
      our understanding of these steps. In this review, after describing the biological
      importance of iron sulfur proteins, we focus on the contributions of NMR
      spectroscopy has made to our understanding of the structures, dynamics, and
      interactions of proteins involved in the biosynthesis of Fe-S cluster proteins.

PMID- 30200363
TI  - Association between Proton Pump Inhibitor Use and CNS Infection Risk: A
      Retrospective Cohort Study.
AB  - This study investigated the incidence of central nervous system (CNS) infection
      following the use of proton pump inhibitors (PPIs). A retrospective cohort study
      was conducted in Taiwan by using data from the National Health Insurance Research
      Database. We identified and enrolled 16,241 patients with CNS infection who used
      PPIs (PPI users). The patients were individually propensity score matched (1:1)
      according to age, sex, hypertension, hyperlipidemia, Charlson comorbidity index
      (CCI), H2 blocker, non-steroidal anti-inflammatory drugs (NSAIDs),
      corticosteroid, and immunosuppressant use with 16,241 controls (PPI nonusers). A
      Cox proportional hazards model was used to estimate adjusted hazard ratio (aHR)
      for CNS infection in the PPI users and nonusers. After adjustment for other
      confounding factors, the incidence of CNS infection in the PPI users was 2.23
      fold higher than that in the PPI nonusers (95% CI = 1.27-3.94). In addition, the
      PPI users exhibited a higher risk of CNS infection than the nonusers in the
      hypertension and CCI = 1 groups (aHR = 3.80, 95% CI = 1.40-10.32; aHR = 2.47, 95%
      CI = 1.07-5.70 in the PPI users and nonusers, respectively). In conclusions,
      according to these results, we concluded that the incidence of CNS infection was
      higher in the PPI users than in the nonusers.

PMID- 30200365
TI  - Dihydromyricetin Attenuates Myocardial Hypertrophy Induced by Transverse Aortic
      Constriction via Oxidative Stress Inhibition and SIRT3 Pathway Enhancement.
AB  - Dihydromyricetin (DMY), one of the flavonoids in vine tea, exerts several
      pharmacological actions. However, it is not clear whether DMY has a protective
      effect on pressure overload-induced myocardial hypertrophy. In the present study,
      male C57BL/6 mice aging 8-10 weeks were subjected to transverse aortic
      constriction (TAC) surgery after 2 weeks of DMY (250 mg/kg/day) intragastric
      administration. DMY was given for another 2 weeks after surgery. Blood pressure,
      myocardial structure, cardiomyocyte cross-sectional area, cardiac function, and
      cardiac index were observed. The level of oxidative stress in the myocardium was
      assessed with dihydroethidium staining. Our results showed that DMY had no
      significant effect on the blood pressure. DMY decreased inter ventricular septum
      and left ventricular posterior wall thickness, relative wall thickness,
      cardiomyocyte cross-sectional areas, as well as cardiac index after TAC. DMY
      pretreatment also significantly reduced arterial natriuretic peptide (ANP), brain
      natriuretic peptide (BNP) mRNA and protein expressions, decreased reactive oxygen
      species production and malondialdehyde (MDA) level, while increased total
      antioxidant capacity (T-AOC), activity of superoxide dismutase (SOD), expression
      of sirtuin 3 (SIRT3), forkhead-box-protein 3a (FOXO3a) and SOD2, and SIRT3
      activity in the myocardium of mice after TAC. Taken together, DMY ameliorated TAC
      induced myocardial hypertrophy in mice related to oxidative stress inhibition and
      SIRT3 pathway enhancement.

PMID- 30200366
TI  - A Three-Stage Accelerometer Self-Calibration Technique for Space-Stable Inertial
      Navigation Systems.
AB  - As a specific force sensor, the tri-axis accelerometer is one of the core
      instruments in an inertial navigation system (INS). During navigation, its
      measurement error directly induces constant or alternating navigation errors of
      the same order of magnitude. Moreover, it also affects the estimation accuracy of
      gyro drift coefficients during the initial alignment and calibration, which will
      indirectly result in navigation errors accumulating over time. Calibration can
      effectively improve measurement accuracy of the accelerometer. Device-level
      calibration can identify all of the parameters in the error model, and the system
      level calibration can accurately estimate part of these parameters. Combining the
      advantages of both the methods and making full use of the precise angulation of
      the space-stabilized platform, this paper proposes a three-stage accelerometer
      self-calibration technique that can be implemented directly in the space-stable
      INS. The device-level calibration is divided into two steps considering the large
      amount of parameters. The first step is coarse calibration, which identifies
      parameters except for the nonlinear terms, and the second step is fine
      calibration, which not only identifies the nonlinear parameters, but also
      improves the accuracy of the parameters identified in the first step. The follow
      on system-level calibration is carried out on part of the parameters using
      specific force error and attitude error to further improve the calibration
      accuracy. Simulation result shows that by using the proposed three-stage
      calibration technique in the space-stable INS, the estimation accuracy of
      accelerometer error can reach 1 * 10 - 6   g order of magnitude. Experiment
      results show that after the three-stage calibration, the accuracy of latitude,
      longitude, and attitude angles has increased by over 45% and the accuracy of
      velocity has increased by over 22% during navigation.

PMID- 30200364
TI  - Phosphate-Catalyzed Succinimide Formation from an NGR-Containing Cyclic Peptide:
      A Novel Mechanism for Deammoniation of the Tetrahedral Intermediate.
AB  - Spontaneous deamidation in the Asn-Gly-Arg (NGR) motif that yields an isoAsp-Gly
      Arg (isoDGR) sequence has recently attracted considerable attention because of
      the possibility of application to dual tumor targeting. It is well known that Asn
      deamidation reactions in peptide chains occur via the five-membered ring
      succinimide intermediate. Recently, we computationally showed by the B3LYP
      density functional theory method, that inorganic phosphate and the Arg side chain
      can catalyze the NGR deamidation using a cyclic peptide, c[CH2CO-NGRC]-NH2. In
      this previous study, the tetrahedral intermediate of the succinimide formation
      was assumed to be readily protonated at the nitrogen originating from the Asn
      side chain by the solvent water before the release of an NH3 molecule. In the
      present study, we found a new mechanism for the decomposition of the tetrahedral
      intermediate that does not require the protonation by an external proton source.
      The computational method is the same as in the previous study. In the new
      mechanism, the release of an NH3 molecule occurs after a proton exchange between
      the peptide and the phosphate and conformational changes. The rate-determining
      step of the overall reaction course is the previously reported first step, i.e.,
      the cyclization to form the tetrahedral intermediate.

PMID- 30200369
TI  - Human Vascular Endothelial Growth Factor A165 Expression Induces the Mouse Model
      of Neovascular Age-Related Macular Degeneration.
AB  - Vascular endothelial growth factor (VEGF) expression induces age-related macular
      degeneration (AMD), which is a common vision-threatening disease due to choroidal
      neovascularization and a fibrovascular membrane. We describe a mouse model of
      neovascular AMD with the local expression of human VEGF-A165 in the eye. We use a
      transgenic mouse in which human VEGF-A165 has been silenced with the loxP-STOP
      fragment. The choroidal neovascularization and human VEGF-A165 expression in the
      mouse are induced by subretinal adenoviral Cre gene delivery. Cre gene transfer
      is compared with adenoviral LacZ gene transfer control. We characterize the AMD
      phenotype and changes in the vasculature by using fluorescein angiography,
      optical coherence tomography, and immunohistochemistry. At early time points,
      mice exhibit increases in retinal thickness (348 +/- 114 um vs. 231 +/- 32 um)
      and choroidal neovascularization area (12000 +/- 15174 um2 vs. 2169 +/- 3495 um2)
      compared with the control. At later time points, choroidal neovascularization
      develops into subretinal fibrovascular membrane. Human VEGF-A165 expression lasts
      several weeks. In conclusion, the retinas display vascular abnormalities
      consistent with choroidal neovascularization. Together with immunohistochemical
      findings, these changes resemble clinical AMD-like ocular pathologies. We
      conclude that this mouse model of Cre-induced choroidal neovascularization is
      useful for mimicking the pathogenesis of AMD, studying the effects of human VEGF
      A165 in the retina, and evaluating anti-VEGF treatments for choroidal
      neovascularization.

PMID- 30200371
TI  - Non-Contact Measurement of the Surface Displacement of a Slope Based on a Smart
      Binocular Vision System.
AB  - The paper presents an intelligent real-time slope surface deformation monitoring
      system based on binocular stereo-vision. To adapt the system to field slope
      monitoring, a design scheme of concentric marking point is proposed. Techniques
      including Zernike moment edge extraction, the least squares method, and k-means
      clustering are used to design a sub-pixel precision localization method for
      marker images. This study is mostly focused on the tracking accuracy of objects
      in multi-frame images obtained from a binocular camera. For this purpose, the
      Upsampled Cross Correlation (UCC) sub-pixel template matching technique is
      employed to improve the spatial-temporal contextual (STC) target-tracking
      algorithm. As a result, the tracking accuracy is improved to the sub-pixel level
      while keeping the STC tracking algorithm at high speed. The performance of the
      proposed vision monitoring system has been well verified through laboratory
      tests.

PMID- 30200368
TI  - Using a Clustering Approach to Investigate Socio-Environmental Inequality in
      Preterm Birth-A Study Conducted at Fine Spatial Scale in Paris (France).
AB  - Background & Objectives: Today, to support public policies aiming to tackle
      environmental and health inequality, identification and monitoring of the spatial
      pattern of adverse birth outcomes are crucial. Spatial identification of the more
      vulnerable population to air pollution may orient health interventions. In this
      context, the objective of this study is to investigate the geographical
      distribution of the risk of preterm birth (PTB, gestational age <=36 weeks) at
      the census block level in in city of Paris, France. We also aimed to assess the
      implication of neighborhood characteristics including air pollution and socio
      economic deprivation. Material & Methods: Newborn health data are available from
      the first birth certificate registered by the Maternal and Child Care department
      of Paris. All PTB from January 2008 to December 2011 were geocoded at the mother
      residential census block. Each census block was assigned a socioeconomic
      deprivation level and annual average ambient concentrations of NO2. A spatial
      clustering approach was used to investigate the spatial distribution of PTB.
      Results: Our results highlight that PTB is non-randomly spatially distributed,
      with a cluster of high risk in the northeastern area of Paris (RR = 1.15; p =
      0.06). After adjustment for socio-economic deprivation and NO2 concentrations,
      this cluster becomes not statistically significant or shifts suggesting that
      these characteristics explain the spatial distribution of PTB; further, their
      combination shows an interaction in comparison with SES or NO2 levels alone.
      Conclusions: Our results may inform the decision makers about the areas where
      public health efforts should be strengthened to tackle the risk of PTB and to
      choose the most appropriate and specific community-oriented health interventions.

PMID- 30200367
TI  - Evaluation of Unconventional Protein Secretion by Saccharomyces cerevisiae and
      other Fungi.
AB  - Development of proteome analysis of extracellular proteins has revealed that a
      wide variety of proteins, including fungal allergens are present outside the
      cell. These secreted allergens often do not contain known secretion signal
      sequences. Recent research progress shows that some fungal allergens are secreted
      by unconventional secretion pathways, including autophagy- and extracellular
      vesicle-dependent pathways. However, secretion pathways remain unknown for the
      majority of extracellular proteins. This review summarizes recent data on
      unconventional protein secretion in Saccharomyces cerevisiae and other fungi.
      Particularly, methods for evaluating unconventional protein secretion are
      proposed for fungal species, including S. cerevisiae, a popular model organism
      for investigating protein secretion pathways.

PMID- 30200372
TI  - A Smart Congestion Control Mechanism for the Green IoT Sensor-Enabled Information
      Centric Networking.
AB  - Information-Centric Networking (ICN) is a new Internet architecture design, which
      is considered as the global-scale Future Internet (FI) paradigm. Though ICN
      offers considerable benefits over the existing IP-based Internet architecture,
      its practical deployment in real life still has many challenges, especially in
      the case of high congestion and limited power in a sensor enabled-network for the
      Internet of Things (IoT) era. In this paper, we propose a smart congestion
      control mechanism to diminish the network congestion rate, reduce sensor power
      consumptions, and enhance the network performance of ICN at the same time to
      realize a complete green and efficient ICN-based sensor networking model. The
      proposed network system uses the chunk-by-chunk aggregated packets according to
      the content popularity to diminish the number of exchanged packets needed for
      data transmission. We also design the sensor power-based cache management
      strategy, and an adaptive Markov-based sensor scheduling policy with selective
      sensing algorithm to further maximize power savings for the sensors. The
      evaluation results using ndnSIM (a widely-used ICN simulator) show that the
      proposed model can provide higher network performance efficiency with lower
      energy consumption for the future Internet by achieving higher throughput with
      higher cache hit rate and lower Interest packet drop rate as we increase the
      number of IoT sensors in ICN.

PMID- 30200370
TI  - Delivering Pediatric Palliative Care: From Denial, Palliphobia, Pallilalia to
      Palliactive.
AB  - Among the over 21 million children with life-limiting conditions worldwide that
      would benefit annually from a pediatric palliative care (PPC) approach, more than
      eight million would need specialized PPC services. In the United States alone,
      more than 42,000 children die every year, half of them infants younger than one
      year. Advanced interdisciplinary pediatric palliative care for children with
      serious illnesses is now an expected standard of pediatric medicine.
      Unfortunately, in many institutions there remain significant barriers to
      achieving optimal care related to lack of formal education, reimbursement issues,
      the emotional impact of caring for a dying child, and most importantly, the lack
      of interdisciplinary PPC teams with sufficient staffing and funding. Data reveals
      the majority of distressing symptoms in children with serious illness (such as
      pain, dyspnea and nausea/vomiting) were not addressed during their end-of-life
      period, and when treated, therapy was commonly ineffective. Whenever possible,
      treatment should focus on continued efforts to control the underlying illness. At
      the same time, children and their families should have access to
      interdisciplinary care aimed at promoting optimal physical, psychological and
      spiritual wellbeing. Persistent myths and misconceptions have led to inadequate
      symptom control in children with life-limiting diseases. Pediatric Palliative
      Care advocates the provision of comfort care, pain, and symptom management
      concurrently with disease-directed treatments. Families no longer have to opt for
      one over the other. They can pursue both, and include integrative care to
      maximize the child's quality of life. Since most of the sickest children with
      serious illness are being taken care of in a hospital, every children's hospital
      is now expected to offer an interdisciplinary palliative care service as the
      standard of care. This article addresses common myths and misconceptions which
      may pose clinical obstacles to effective PPC delivery and discusses the four
      typical stages of pediatric palliative care program implementation.

PMID- 30200374
TI  - Physical Activity and Fundamental Motor Skill Performance of 5-10 Year Old
      Children in Three Different Playgrounds.
AB  - Playgrounds provide opportunities for children to engage in physical activity and
      develop their fundamental motor skills. The aim of this descriptive pilot study
      was to examine whether playground design facilitated different levels of physical
      activity and fundamental motor skills. Children aged 5 to 10 (n = 57) were
      recruited from three independent playgrounds located in Melbourne (Australia).
      Whilst playing, children wore accelerometers which measured time spent in
      physical activity and direct observations recorded fundamental motor skills and
      play equipment use. A general linear model with playground type as the predictor
      and adjusting for monitor wear-time identified whether mean time in physical
      activity was different for the three playgrounds. Frequencies and a one-way ANOVA
      assessed whether the observed mean number of fundamental motor skills varied
      between playgrounds. On average, 38.1% of time (12.0 min) was spent in moderate-
      vigorous-intensity physical activity. Children in the traditional playground (n =
      16) engaged in more moderate-intensity physical activity (9.4 min) than children
      in the adventure playground (n = 21), (5.6 min) (p = 0.027). There were no
      significant associations with vigorous-intensity physical activity or fundamental
      motor skills between playgrounds. Children performed few fundamental motor skills
      but used a wider variety of equipment in the contemporary and adventure
      playgrounds. Playgrounds need to maximise opportunities for children to engage in
      physical activity and develop fundamental motor skills.

PMID- 30200375
TI  - Energy Efficient Policies for Data Transmission in Disruption Tolerant
      Heterogeneous IoT Networks.
AB  - The Internet-of-things facilitates the development of many groundbreaking
      applications. A large number of these applications involve mobile end nodes and a
      sparsely deployed network of base stations that operate as gateways to the
      Internet. Most of the mobile nodes, at least within city areas, are connected
      through low power wide area networking technologies (LPWAN) using public
      frequencies. Mobility and sparse network coverage result in long delays and
      intermittent connectivity for the end nodes. Disruption Tolerant Networks and
      utilization of heterogeneous wireless interfaces have emerged as key technologies
      to tackle the problem at hand. The first technology renders communication
      resilient to intermittent connectivity by storing and carrying data while the
      later increases the communication opportunities of the end nodes and at the same
      time reduces energy consumption whenever short-range communication is possible.
      However, one has to consider that end nodes are typically both memory and energy
      constrained devices which makes finding an energy efficient data transmission
      policy for heterogeneous disruption tolerant networks imperative. In this work we
      utilize information related to the spatial availability of network resources and
      localization information to formulate the problem at hand as a dynamic
      programming problem. Next, we utilize the framework of Markov Decision Processes
      to derive approximately optimal and suboptimal data transmission policies. We
      also prove that we can achieve improved packet transmission policies and reduce
      energy consumption, extending battery lifetime. This is achieved by knowing the
      spatial availability of heterogeneous network resources combined with the mobile
      node's location information. Numerical resultsshow significant gains achieved by
      utilizing the derived approximately optimal and suboptimal policies.

PMID- 30200376
TI  - Spatial Distribution and Contamination Assessment of Surface Heavy Metals off the
      Western Guangdong Province and Northeastern Hainan Island.
AB  - Surface sediments collected from the continental shelf off the western Guangdong
      Province and northeastern Hainan Island are analyzed for selected heavy metals
      contents including Cd, Cr, Cu, Pb, Zn, and As to determine spatial distribution,
      potential ecological risks, and sources. In addition, some of the controlling
      factors of heavy metals distribution are also discussed. The average heavy metals
      contents decrease in the order of Zn > Cr > Pb > Cu > As > Cd. The averaged
      pollution degree, as shown by the index of geo-accumulation (Igeo), decreases in
      the order of Zn > Cu > Pb > Cr > Cd > As. Due to the barrier of islands, the Igeo
      values of Zn, Pb, Cr, Cu, and Cd near the Hailing and Xiachuan Islands are larger
      than those in other areas. Meanwhile, the Igeo value of As near the coastal area
      off the estuary of Wanquan River is clearly larger than that in other areas.
      Based on the results of potential ecological risk index, Cd, Cu, and As should be
      paid more attention for the contamination risk in future. The results of Pearson
      correlation analysis and principal component analysis indicate that Zn, Cr, Pb,
      Cu, and Cd are mainly from the Pearl River and surrounding small rivers, whereas
      As originates from the Hainan Island. The grain size is one of the main
      controlling factors for heavy metals distribution, and the anthropogenic activity
      also plays an important role.

PMID- 30200373
TI  - Biomedical Applications of Silver Nanoparticles: An Up-to-Date Overview.
AB  - During the past few years, silver nanoparticles (AgNPs) became one of the most
      investigated and explored nanotechnology-derived nanostructures, given the fact
      that nanosilver-based materials proved to have interesting, challenging, and
      promising characteristics suitable for various biomedical applications. Among
      modern biomedical potential of AgNPs, tremendous interest is oriented toward the
      therapeutically enhanced personalized healthcare practice. AgNPs proved to have
      genuine features and impressive potential for the development of novel
      antimicrobial agents, drug-delivery formulations, detection and diagnosis
      platforms, biomaterial and medical device coatings, tissue restoration and
      regeneration materials, complex healthcare condition strategies, and performance
      enhanced therapeutic alternatives. Given the impressive biomedical-related
      potential applications of AgNPs, impressive efforts were undertaken on
      understanding the intricate mechanisms of their biological interactions and
      possible toxic effects. Within this review, we focused on the latest data
      regarding the biomedical use of AgNP-based nanostructures, including aspects
      related to their potential toxicity, unique physiochemical properties, and
      biofunctional behaviors, discussing herein the intrinsic anti-inflammatory,
      antibacterial, antiviral, and antifungal activities of silver-based
      nanostructures.

PMID- 30200377
TI  - Feature Representation and Data Augmentation for Human Activity Classification
      Based on Wearable IMU Sensor Data Using a Deep LSTM Neural Network.
AB  - Wearable inertial measurement unit (IMU) sensors are powerful enablers for
      acquisition of motion data. Specifically, in human activity recognition (HAR),
      IMU sensor data collected from human motion are categorically combined to
      formulate datasets that can be used for learning human activities. However,
      successful learning of human activities from motion data involves the design and
      use of proper feature representations of IMU sensor data and suitable
      classifiers. Furthermore, the scarcity of labelled data is an impeding factor in
      the process of understanding the performance capabilities of data-driven learning
      models. To tackle these challenges, two primary contributions are in this
      article: first; by using raw IMU sensor data, a spectrogram-based feature
      extraction approach is proposed. Second, an ensemble of data augmentations in
      feature space is proposed to take care of the data scarcity problem. Performance
      tests were conducted on a deep long term short term memory (LSTM) neural network
      architecture to explore the influence of feature representations and the
      augmentations on activity recognition accuracy. The proposed feature extraction
      approach combined with the data augmentation ensemble produces state-of-the-art
      accuracy results in HAR. A performance evaluation of each augmentation approach
      is performed to show the influence on classification accuracy. Finally, in
      addition to using our own dataset, the proposed data augmentation technique is
      evaluated against the University of California, Irvine (UCI) public online HAR
      dataset and yields state-of-the-art accuracy results at various learning rates.

PMID- 30200378
TI  - Top-Down NOX Emissions of European Cities Based on the Downwind Plume of Modelled
      and Space-Borne Tropospheric NO2 Columns.
AB  - Top-down estimates of surface NOX emissions were derived for 23 European cities
      based on the downwind plume decay of tropospheric nitrogen dioxide (NO2) columns
      from the LOTOS-EUROS (Long Term Ozone Simulation-European Ozone Simulation)
      chemistry transport model (CTM) and from Ozone Monitoring Instrument (OMI)
      satellite retrievals, averaged for the summertime period (April-September) during
      2013. Here we show that the top-down NOX emissions derived from LOTOS-EUROS for
      European urban areas agree well with the bottom-up NOX emissions from the MACC
      III inventory data (R2 = 0.88) driving the CTM demonstrating the potential of
      this method. OMI top-down NOX emissions over the 23 European cities are generally
      lower compared with the MACC-III emissions and their correlation is slightly
      lower (R2 = 0.79). The uncertainty on the derived NO2 lifetimes and NOX emissions
      are on average ~55% for OMI and ~63% for LOTOS-EUROS data. The downwind NO2 plume
      method applied on both LOTOS-EUROS and OMI tropospheric NO2 columns allows to
      estimate NOX emissions from urban areas, demonstrating that this is a useful
      method for real-time updates of urban NOX emissions with reasonable accuracy.

PMID- 30200379
TI  - Oral Biofilms: Development, Control, and Analysis.
AB  - The oral cavity harbors hundreds of microbial species that are present either as
      planktonic cells or incorporated into biofilms. The majority of the oral microbes
      are commensal organisms. Those that are pathogenic microbes can result in oral
      infections, and at times can initiate systemic diseases. Biofilms that contain
      pathogens are challenging to control. Many conventional antimicrobials have
      proven to be ineffective. Recent advances in science and technology are providing
      new approaches for pathogen control and containment and methods to characterize
      biofilms. This perspective provides (1) a general understanding of biofilm
      development; (2) a description of emerging chemical and biological methods to
      control oral biofilms; and (3) an overview of high-throughput analytical
      approaches to analyze biofilms.

PMID- 30200381
TI  - An Integrated Dead Reckoning with Cooperative Positioning Solution to Assist GPS
      NLOS Using Vehicular Communications.
AB  - In Intelligent Transportation Systems (ITS), the Vehicular Ad Hoc Networks
      (VANETs) paradigm based on the WAVE IEEE 802.11p standard is the main alternative
      for inter-vehicle communications. Recently, many protocols, applications, and
      services have been developed with a wide range of objectives, ranging from
      comfort to security. Most of these services rely on location systems and require
      different levels of accuracy for their full operation. The Global Positioning
      System (GPS) is an off-the-shelf solution for localization in VANETs and ITS.
      However, GPS systems present problems regarding inaccuracy and unavailability in
      dense urban areas, multilevel roads, and tunnels, posing a challenge for
      protocols, applications, and services that rely on localization. With this
      motivation, we carried out a characterization of the problems of inaccuracy and
      unavailability of GPS systems from real datasets, and regions around tunnels were
      selected. Since the nodes of the vehicular network are endowed with wireless
      communication, processing and storage capabilities, an integrated Dead Reckoning
      aided Geometric Dilution of Precision (GDOP)-based Cooperative Positioning
      solution was developed and evaluated. Leveraging the potential of vehicular
      sensors, such as odometers, gyroscopes, and digital compasses, vehicles share
      their positions and kinematics information using vehicular communication to
      improve their location estimations. With the assistance of a digital map,
      vehicles adjust the final estimated position using the road geometry. The
      situations of GPS unavailability characterized in the datasets were reproduced in
      a simulation environment to validate the proposed localization solution. The
      simulation results show average gains in Root Mean Square Error (RMSE) between
      97% to 98% in comparison with the stand-alone GPS solution, and 83.00% to 88.00%
      against the GPS and Dead Reckoning (DR) only solution. The average absolute RMSE
      was reduced to the range of 3 to 5 m by vehicle. In addition, the proposed
      solution was shown to support 100% of the GPS unavailability zones on the
      evaluated scenarios.

PMID- 30200380
TI  - Integrating Gaze Tracking and Head-Motion Prediction for Mobile Device
      Authentication: A Proof of Concept.
AB  - We introduce a two-stream model to use reflexive eye movements for smart mobile
      device authentication. Our model is based on two pre-trained neural networks,
      iTracker and PredNet, targeting two independent tasks: (i) gaze tracking and (ii)
      future frame prediction. We design a procedure to randomly generate the visual
      stimulus on the screen of mobile device, and the frontal camera will
      simultaneously capture head motions of the user as one watches it. Then, iTracker
      calculates the gaze-coordinates error which is treated as a static feature. To
      solve the imprecise gaze-coordinates caused by the low resolution of the frontal
      camera, we further take advantage of PredNet to extract the dynamic features
      between consecutive frames. In order to resist traditional attacks (shoulder
      surfing and impersonation attacks) during the procedure of mobile device
      authentication, we innovatively combine static features and dynamic features to
      train a 2-class support vector machine (SVM) classifier. The experiment results
      show that the classifier achieves accuracy of 98.6% to authenticate the user
      identity of mobile devices.

PMID- 30200382
TI  - An Effective and Secure Key Management Protocol for Message Delivery in
      Autonomous Vehicular Clouds.
AB  - Autonomous vehicular clouds, as the combination of cloud computing and
      conventional vehicular ad hoc networks, will provide abundant resources and
      services by sharing under-utilized resources of future high-end vehicles such as
      computing power, storage and internet connectivity. Autonomous vehicular clouds
      will have significant impact if widely implemented in the intelligent
      transportation system. However, security and privacy issues are still big
      challenges in autonomous vehicular clouds. In this paper, after analyzing the
      particularity of autonomous vehicular clouds, we implement a two-layered
      architecture, in which vehicles are self-organized without the help of roadside
      units. Then based on the architecture, we put forward an effective key management
      protocol to distribute a group key efficiently and also provide the
      authentication and confidentiality that lots of current secure schemes ignore. In
      addition, according to the different scenarios and security levels we categorize
      the way of message transmitting into three kinds. At last, with performance
      evaluations, the proposed protocol can perform more efficiently than other well
      known available schemes.

PMID- 30200384
TI  - Countermovement Jump Analysis Using Different Portable Devices: Implications for
      Field Testing.
AB  - The aim of this study was to analyze the concurrent validity, test-retest
      reliability, and capacity to detect changes of four different portable devices
      used to measure a wide range of neuromuscular parameters derived from
      countermovement jump (CMJ). An accelerometric device (Myotest), a jump mat
      (Ergojump), an optical device (Optojump), and a smartphone app (MyJump) were
      simultaneously examined for concurrent validity against gold-standard measures
      (motion-capture system and a force platform). Twenty-two CMJ-derived variables
      were collected from 15 healthy male subjects (n = 60 CMJs). Contraction time (CT)
      and eccentric duration (EccD) measurements obtained from the Myotest were
      moderately to largely associated with and not different from force platform
      measurements (r = 0.31 to 0.64, ES = 0.11 to 0.18) and showed moderate test
      retest reliability (intraclass correlation coefficient (ICC) = 0.92 to 0.97,
      coefficient of variation (CV) = 3.8 to 8.0%). Flight time (FT) and jump height
      (JH) from Ergojump, Optojump, and MyJump showed moderate to strong associations
      with gold-standard measurements (r = 0.57 to 0.98) and good test-retest
      reliability (ICC = 0.54 to 0.97, CV = 1.8 to 4.2). However, all portable devices
      underestimated JH (ES = 1.25 to 2.75). Independent of the instrument used, the
      analyzed CMJ variables showed good capacity to detect changes (standard error of
      measurement (SEM) < smallest worthwhile change (SWC)), with the exception of rate
      of force and rate of power development parameters, which showed marginal capacity
      (SEM > SWC). The Myotest is preferable to measure temporal parameters during
      ground contact, whereas Ergojump, Optojump, and MyJump devices may be preferable
      to measure FT and JH, with the Optojump being the most accurate.

PMID- 30200383
TI  - Effects of Dietary Fibre from the Traditional Indonesian Food, Green Cincau
      (Premna oblongifolia Merr.) on Preneoplastic Lesions and Short Chain Fatty Acid
      Production in an Azoxymethane Rat Model of Colon Cancer.
AB  - Green cincau (Premna oblongifolia Merr.) is a traditional food of Indonesia and
      provides a natural source of dietary fibre and antioxidants. This study evaluated
      the ability of green cincau, and other dietary fibres with or without the
      addition of anti-oxidant, epigallocatechin-3-gallate (EGCG), to prevent
      colorectal cancer in a 12 week azoxymethane (AOM) rat model. While all dietary
      treatments stimulated short chain fatty acid production (SCFA) in the digesta and
      faeces, no one treatment was able to significantly protect against aberrant crypt
      formation (ACF), when compared to the control diet. However, feeding green cincau
      leaves or extracts did not result in an increase in ACF compared to the control
      diet. Unexpectedly, when the dietary fibre source was pectin, 0.1% EGCG increased
      proliferative activity and liver lipid peroxidation when compared to the control
      diet containing cellulose. Examination of faecal microbial communities identified
      the presence of short chain acid producing bacteria, but a distinct community
      profile was not observed from any individual diet group. Overall, this research
      implies that combining dietary fibre with an antioxidant does not automatically
      equate to a beneficial response. Further work is required to investigate the
      health-promoting properties of green cincau.

PMID- 30200385
TI  - Properties of Lithium Trivanadate Film Electrodes Formed on Garnet-Type Oxide
      Solid Electrolyte by Aerosol Deposition.
AB  - We fabricated lithium trivanadate LiV3O8 (LVO) film electrodes for the first time
      on a garnet-type Ta-doped Li7La3Zr2O12 (LLZT) solid electrolyte using the aerosol
      deposition (AD) method. Ball-milled LVO powder with sizes in the range of 0.5-2
      um was used as a raw material for LVO film fabrication via impact consolidation
      at room temperature. LVO film (thickness = 5 um) formed by AD has a dense
      structure composed of deformed and fractured LVO particles and pores were not
      observed at the LVO/LLZT interface. For electrochemical characterization of LVO
      film electrodes, lithium (Li) metal foil was attached on the other end face of a
      LLZT pellet to comprise a LVO/LLZT/Li all-solid-state cell. From impedance
      measurements, the charge transfer resistance at the LVO/LLZT interface is
      estimated to be around 103 Omega cm2 at room temperature, which is much higher
      than at the Li/LLZT interface. Reversible charge and discharge reactions in the
      LVO/LLZT/Li cell were demonstrated and the specific capacities were 100 and 290
      mAh g-1 at 50 and 100  degrees C. Good cycling stability of electrode reaction
      indicates strong adhesion between the LVO film electrode formed via impact
      consolidation and LLZT.

PMID- 30200387
TI  - Equilibrium and Kinetic Study of Lead and Copper Ion Adsorption on Chitosan
      Grafted-Polyacrylic Acid Synthesized by Surface Initiated Atomic Transfer
      Polymerization.
AB  - In this work, we synthesized chitosan grafted-polyacrylic acid (CS-g-PA) through
      surface-initiated atom transfer radical polymerization (SI-ATRP). We also studied
      the adsorption process of copper and lead ions onto the CS-g-PA surface.
      Adsorption equilibrium studies indicated that pH 4.0 was the best pH for the
      adsorption process and the maximum adsorption capacity over CS-g-PA for Pb2+ ions
      was 98 mg.g-1 and for Cu2+ it was 164 mg.g-1, while for chitosan alone (CS), the
      Pb2+ adsorption capacity was only 14.8 mg.g-1 and for Cu2+ it was 140 mg.g-1.
      Furthermore, the adsorption studies indicated that Langmuir model describes all
      the experimental data and besides, pseudo-second-order model was suitable to
      describe kinetic results for the adsorption process, demonstrating a larger
      kinetic constant of the process was larger for Pb2+ than Cu2+. Compared to other
      adsorbents reported, CS-g-PA had comparable or even superior adsorbent capacity
      and besides, all these results suggest that the new CS-g-PA polymers had
      potential as an adsorbent for hazardous and toxic metal ions produced by
      different industries.

PMID- 30200386
TI  - Th1-Biased Immunomodulation and In Vivo Antitumor Effect of a Novel Piperine
      Analogue.
AB  - Natural products have an important role as prototypes in the synthesis of new
      anticancer drugs. Piperine is an alkaloid amide with antitumor activity and
      significant toxicity. Then, the N-(p-nitrophenyl)acetamide piperinoate (HE-02)
      was synthesized, and tested for toxicological and antitumor effects. The toxicity
      was evaluated in vitro (on RAW 264.7 cells and mice erythrocytes) and in vivo
      (acute toxicity in mice). The Ehrlich ascites carcinoma model was used to
      evaluate the antitumor activity of HE-02 (6.25, 12.5 or 25 mg/kg,
      intraperitoneally, i.p.), as well as toxicity. HE-02 induced only 5.01% of
      hemolysis, and reduced the viability of RAW 264.7 cells by 49.75% at 1000 ug/mL.
      LD50 (lethal dose 50%) was estimated at around 2000 mg/kg (i.p.). HE-02 reduced
      Ehrlich tumor cell viability and peritumoral microvessels density. There was an
      increase of Th1 helper T lymphocytes cytokine profile levels (IL-1beta, TNF
      alpha, IL-12) and a decrease of Th2 cytokine profile (IL-4, IL-10). Moreover, an
      increase was observed on reactive oxygen species and nitric oxide production.
      Weak in vivo toxicological effects were recorded. Our data provide evidence that
      the piperine analogue HE-02 present low toxicity, and its antitumor effect
      involves modulation of immune system to a cytotoxic Th1 profile.

PMID- 30200388
TI  - Insomnia in Adolescence.
AB  - Adolescent insomnia is a common condition that negatively impacts a developing
      young adult's mental and physical health. While the treatment of adult insomnia
      has been standardized, the treatment of pediatric insomnia is very practitioner
      dependent and few large-scale studies are available to determine a standard
      recommended practice. There is great hope that as the adolescent medicine and
      sleep medicine fields flourish, larger cohort analyses will be performed to
      determine the prevalence and precipitating factors of adolescent insomnia,
      allowing for standardized treatment recommendations and systematic efforts to
      make these recommendations available to all adolescents.

PMID- 30200389
TI  - Morphological Type Identification of Self-Incompatibility in Dendrobium and Its
      Phylogenetic Evolution Pattern.
AB  - Self-incompatibility (SI) is a type of reproductive barrier within plant species
      and is one of the mechanisms for the formation and maintenance of the high
      diversity and adaptation of angiosperm species. Approximately 40% of flowering
      plants are SI species, while only 10% of orchid species are self-incompatible.
      Intriguingly, as one of the largest genera in Orchidaceae, 72% of Dendrobium
      species are self-incompatible, accounting for nearly half of the reported SI
      species in orchids, suggesting that SI contributes to the high diversity of
      orchid species. However, few studies investigating SI in Dendrobium have been
      published. This study aimed to address the following questions: (1) How many SI
      phenotypes are in Dendrobium, and what are they? (2) What is their distribution
      pattern in the Dendrobium phylogenetic tree? We investigated the flowering time,
      the capsule set rate, and the pollen tube growth from the representative species
      of Dendrobium after artificial pollination and analysed their distribution in the
      Asian Dendrobium clade phylogenetic tree. The number of SI phenotypes exceeded
      our expectations. The SI type of Dendrobium chrysanthum was the primary type in
      the Dendrobium SI species. We speculate that there are many different SI
      determinants in Dendrobium that have evolved recently and might be specific to
      Dendrobium or Orchidaceae. Overall, this work provides new insights and a
      comprehensive understanding of Dendrobium SI.

PMID- 30200390
TI  - 1-Kestose, the Smallest Fructooligosaccharide Component, Which Efficiently
      Stimulates Faecalibacterium prausnitzii as Well as Bifidobacteria in Humans.
AB  - The concept of prebiotics was established more than 30 years ago. While the
      prebiotic concept has now expanded thus includes non-carbohydrate substances and
      diverse categories other than foods, fructooligosaccharides (FOS) have still
      predominantly been used as pebiotics, because the effects of FOS exclusively act
      through the enrichment of Bifidobacterium and Lactobacillus spp., which have been
      classified as beneficial intestinal commensals so far. Now the commercially
      available FOS products are synthetic mixture of several kinds of FOS components
      including 1-kestose (GF2), nystose (GF3) and GF4. In our previous studies,
      superiority of 1-kestose to the longer-chain FOS components such as nystose with
      regard to bifidogenic activity was clearly demonstrated. Recently, a broader
      range of beneficial bacteria including butyrate-producing indigenous bacteria
      have been recognized and expected to be new probiotic strains. Among them,
      resident Faecalibacterium prausnitzii is a butyrate producer with a significant
      anti-inflammatory effect thus expected to be useful as a next-generation
      probiotic. However, this bacterium is extremely oxygen-sensitive thus can be
      difficult to grow industrially. On the other hand, we have clearly demonstrated a
      significant prebiotic effect of 1-kestose, which is the smallest component of
      FOS, on F. prausnitzii in the gut of humans. These findings suggest that 1
      kestose has impressive potential as a new prebiotic targeting F. prausnitzii, a
      next-generation probiotic strain, as well as bifidobacteria.

PMID- 30200391
TI  - Effects of the Plastic of the Realistic GeePS-L2S-Breast Phantom.
AB  - A breast phantom developed at the Supelec Institute was interrogated to study its
      suitability for microwave tomography measurements. A microwave measurement system
      based on 16 monopole antennas and a vector network analyzer was used to study how
      the S-parameters are influenced by insertion of the phantom. The phantom is a 3D
      printed structure consisting of plastic shells that can be filled with tissue
      mimicking liquids. The phantom was filled with different liquids and tested with
      the measurement system to determine whether the plastic has any effects on the
      recovered images or not. Measurements of the phantom when it is filled with the
      same liquid as the surrounding coupling medium are of particular interest. In
      this case, the phantom plastic has a substantial effects on the measurements
      which ultimately detracts from the desired images.

PMID- 30200392
TI  - The Genotoxicity of Caecal Water in Gilts Exposed to Low Doses of Zearalenone.
AB  - Zearalenone is a toxic low-molecular-weight molecule that is naturally produced
      by moulds on crops as a secondary metabolite. The aim of this study was to
      determine the genotoxicity of caecal water collected successively from the caecal
      contents of gilts exposed to low doses (LOAEL, NOAEL, and MABEL) of zearalenone.
      The experiment was performed on 60 clinically healthy gilts with average BW of
      14.5 +/- 2 kg, divided into three experimental groups and a control group. Group
      ZEN5 were orally administered ZEN at 5 MUg/kg BW, group ZEN10-10 MUg ZEN/kg BW
      and group ZEN15-15 ug ZEN/kg BW. Five gilts from every group were euthanized on
      analytical dates 1, 2, and 3. Caecal water samples for in vitro analysis were
      collected from the ileocaecal region. The genotoxicity of caecal water was noted,
      particularly after date 1 in groups ZEN10 and ZEN15 with a decreasing trend.
      Electrophoresis revealed the presence of numerous comets without tails in groups
      C and ZEN5 and fewer comets with clearly expressed tails in groups ZEN10 and
      ZEN15. The distribution of LLC-PK1 cells ranged from 15% to 20% in groups C and
      ZEN5, and from 30% to 60% in groups ZEN10 and ZEN15. The analysis of caecal water
      genotoxicity during exposure to very low doses of ZEN revealed the presence of a
      counter response and a compensatory effect in gilts.

PMID- 30200393
TI  - Osteonecrosis of the Jaw in Myeloma Patients Receiving Denosumab or Zoledronic
      Acid. A Commentary of the Pivotal Trial by Raje et al. Published on Lancet
      Oncology.
AB  - The recent randomized trial, published by Raje et al., on Lancet Oncology is
      potentially practice changing. It proposes that denosumab is a valid alternative
      to zoledronic acid in the treatment of myeloma patients. However, several points
      need further data and more details, such as information on incidence, diagnosis,
      and follow-up of osteonecrosis of the jaw (ONJ) cases, observed among treated
      patients. Adopted definition to adjudicate ONJ cases, type of registration of
      potential ONJ cases, length of observation are possible causes of potential
      underestimation of ONJ incidence in their study. Future updated evaluations with
      longer follow-up, and including actuarial estimation, are required for final
      judgment on ONJ risk in myeloma patients receiving denosumab, and comparison with
      ONJ risk by zoledronic acid.

PMID- 30200394
TI  - Efficacy of an Oral Rehydration Solution Enriched with Lactobacillus reuteri DSM
      17938 and Zinc in the Management of Acute Diarrhoea in Infants: A Randomized,
      Double-Blind, Placebo-Controlled Trial.
AB  - The efficacy of oral rehydration solution (ORS) enriched with Lactobacillus
      reuteri DSM 17938 and zinc in infants with acute gastroenteritis, is poorly
      defined. The aim of this double-blind, randomized, placebo-controlled study, was
      to assess the efficacy of an ORS enriched with Lactobacillus reuteri DSM 17938
      and zinc (ORS+Lr&Z) in well-nourished, non-hospitalized infants with acute
      diarrhoea. Fifty one infants with acute diarrhoea were randomly assigned to
      receive either ORS+Lr&Z (28 infants, mean +/- SD age 1.7 +/- 0.7 years, 21
      males), or standard ORS (ORS-Lr&Z; 23 infants, mean +/- SD age 1.8 +/- 0.7 years,
      16 males). Stools volume and consistency were recorded pre- and posttreatment
      using the Amsterdam Infant Stool Scale and were compared between the two groups,
      as well as lost work/day care days, drug administration and need for
      hospitalization. Both groups showed reduction in the severity of diarrhoea on day
      two (p < 0.001) while, all outcomes showed a trend to be better in the ORS+Lr&Z
      group, without reaching statistical significance, probably due to the relatively
      small number of patients. No adverse effects were recorded. In conclusion, both
      ORS were effective in managing acute diarrhoea in well-nourished, non
      hospitalized infants. ORS enriched with L. reuteri DSM 17938 and zinc was well
      tolerated with no adverse effects.

PMID- 30200395
TI  - Ring Wrinkle Patterns with Continuously Changing Wavelength Produced Using a
      Controlled-Gradient Light Field.
AB  - We report a facile method to prepare gradient wrinkles using a controlled
      gradient light field. Because of the gradient distance between the ultraviolet
      (UV) lamp and polydimethylsiloxane (PDMS) substrate during UV/ozone treatment,
      the irradiance reaching the substrate continuously changed, which was transferred
      into the resulting SiOx film with a varying thickness. Therefore, wrinkles with
      continuously changing wavelength were fabricated using this approach. It was
      found that the wrinkle wavelength decreased as the distance increased. We
      fabricated 1-D wrinkle patterns and ring wrinkles with a gradient wavelength. The
      ring wrinkles were prepared using radial stresses, which were achieved by pulling
      the center of a freely hanging PDMS film. The resulting wrinkles with changing
      wavelength can be used in fluid handling systems, biological templates, and
      optical devices.

PMID- 30200397
TI  - The Aerosol Deposition Method: A Modified Aerosol Generation Unit to Improve
      Coating Quality.
AB  - Owing to its ability to produce dense thick-films at room temperature directly
      from a ceramic powder, the Aerosol Deposition Method (AD) possesses a unique
      feature in ceramics processing. For this technology, the aerosol generation of
      particles is a decisive part of reliable process control. However, there has only
      been a small amount of work published addressing this topic. In this work, we
      compare the aerosolization and deposition behavior of a fluidized bed generator
      with an aerosol generator with the rotary brush principle. While film properties
      very much depend on deposition time for the fluidized bed generator, films
      produced with the brush generator show a constant film profile, and their film
      thickness correlates with the controllable aerosol concentration and the duration
      of deposition. This type of aerosol generation may improve the setup towards a
      more reliable AD process.

PMID- 30200396
TI  - Optimization of Flavonoids Extraction Process in Panax notoginseng Stem Leaf and
      a Study of Antioxidant Activity and Its Effects on Mouse Melanoma B16 Cells.
AB  - The Panax notoginseng (P. notoginseng) stem leaf is rich in flavonoids. However,
      because of a lack of research on the flavonoid extraction process and functional
      development of P. notoginseng stem leaf, these parts are discarded as
      agricultural wastes. Therefore, in this study, we intend to optimize the
      extraction process and develop the skin-whitening functions of P. notoginseng
      stem leaf extracts. The extraction process of the stem and leaf of P. notoginseng
      flavonoid (SLPF) is optimized based on the Box-Behnken design (BBD) and the
      response surface methodology (RSM). The optimum extraction conditions of the SLPF
      are as follows: the extraction time, the ethanol concentration, the sodium
      dodecyl sulfate (SDS) content and the liquid material ratio (v/w, which are 52
      min, 48.7%, 1.9%, and 20:1, respectively. Under the optimal extraction
      conditions, the average total SLPF content is 2.10%. The antioxidant activity and
      anti-deposition of melanin of mouse B16 cells of P. notoginseng stem leaf
      extracts are studied. The results indicate that the EC50 values of reducing
      activity, 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging
      activities, the superoxide anion removal ability, and the 2,2-azino-bis-3
      ethylbenzthiazoline-6-sulphonic acid (ABTS) free radical removal ability are
      7.212, 2.893, 2.949, and 0.855 mg/mL, respectively. The extracts IC50 values of
      the tyrosinase and melanin synthesis are 0.045 and 0.046 mg/mL, respectively.
      Therefore, the optimal processing technology for the SLPF obtained in this study
      not only increases its utilization rate, but also decreases material costs. The
      extracts from the P. notoginseng stem leaf may be developed as food or beauty
      products.

PMID- 30200398
TI  - Daily Consumption of Chocolate Rich in Flavonoids Decreases Cellular Genotoxicity
      and Improves Biochemical Parameters of Lipid and Glucose Metabolism.
AB  - In recent years, the incidence of atherosclerotic cardiovascular disease,
      obesity, and diabetes has increased largely worldwide. In the present work, we
      evaluated the genoprotective effect of the consumption of flavonoids-rich
      chocolate on 84 young volunteers. Biochemical indicators related to the
      prevention and treatment of cardiovascular risk and metabolic syndrome were also
      determined. A randomized, placebo-controlled, double-blind study was performed in
      the Autonomous University of Baja California. The treatments comprised the daily
      consumption of either 2 g of dark chocolate containing 70% cocoa, or 2 g of milk
      chocolate, for 6 months. The total amount of phenolic compounds and flavonoids
      was determined in both types of chocolate. Anthropometrical and Biochemical
      parameters were recorded prior to and after the study. The evaluation of the
      genotoxicity in buccal epithelial cells was performed throughout the duration of
      the study. Flavonoids from cocoa in dark chocolate significantly prevented DNA
      damage, and improved the nucleus integrity of cells. This effect could be related
      to the antioxidant capacity of the dark chocolate that decreased cellular stress.
      Biochemical parameters (total cholesterol, triglycerides, and LDL-cholesterol
      level in blood) and anthropometrical parameters (waist circumference) were
      improved after six months of daily intake of 2 g of dark chocolate with a 70% of
      cocoa.

PMID- 30200399
TI  - Methionine Partially Replaced by Methionyl-Methionine Dipeptide Improves
      Reproductive Performance over Methionine Alone in Methionine-Deficient Mice.
AB  - Decreased protein breakdown in pregnant women results in lower concentration of
      methionine (Met) in plasma, causing pregnancy-related metabolic disturbance. Its
      dipeptide methionyl-methionine (Met-Met) may exert positive influence in fetal
      development. This study mainly investigated whether Met-Met can be used as part
      of free Met to promote reproductive outcomes in mice and the underlying
      mechanisms. Met-deficient pregnant mice were treated with Met alone or with Met
      Met during pregnancy. Daily intraperitoneal injection of 35% dietary Met in
      pregnant mice was the best dose among the 15-45% doses. Embryo development and
      newborn birth weight were enhanced when 25% of the Met in the 35% Met group was
      replaced with Met-Met. Met-Met replacement had higher plasma insulin, glucose,
      and free amino acids (AA) concentrations. Besides, in the placenta, the AA
      transporter mRNA abundances and peptide transporters (PhT1 and PepT1) protein
      levels were higher in Met-Met treatment group. Moreover, Met-Met increased 4E
      BP1, S6K1 and AKT/mTOR phosphorylation. These results suggest that Met-Met could
      be used as a partial source of Met to promote reproductive outcomes in Met
      restricted pregnant mice, which might be mediated by promoting nutrient
      availability and activating AKT/mTOR-mediated signaling pathway.

PMID- 30200400
TI  - alpha-Glucosidase Inhibitors: Diphenyl Ethers and Phenolic Bisabolane
      Sesquiterpenoids from the Mangrove Endophytic Fungus Aspergillus flavus QQSG-3.
AB  - Two new diphenyl ethers (1 and 2) and four new phenolic bisabolane
      sesquiterpenoids (3-6), together with five known related derivatives, were
      isolated from the culture of the endophytic fungus Aspergillus flavus QQSG-3
      obtained from a fresh branch of Kandelia obobata, which was collected from
      Huizhou city in the province of Guangdong, China. The structures of compounds 1-6
      were determined by analyzing NMR and HRESIMS data. The absolute configurations of
      5 and 6 were assigned by comparing their experimental ECD spectra with those
      reported for similar compounds in the literature. All isolates were evaluated for
      their alpha-glucosidase inhibitory activity, of which compounds 3, 5, 10, and 11
      showed strong inhibitory effects with IC50 values in the range of 1.5-4.5 MUM.

PMID- 30200401
TI  - Royal Jelly Delays Motor Functional Impairment During Aging in Genetically
      Heterogeneous Male Mice.
AB  - Aging is associated with motor disorders that decrease the quality of life (QOL).
      Royal jelly (RJ), used as a dietary supplement, has shown various health benefits
      and, therefore, it has the potential to improve the QOL during aging. We have
      previously developed protease enzyme-treated RJ to avoid the anaphylactic
      response induced by RJ supplementation. However, the effects of a lifelong
      treatment with RJ on normal aging have not been fully clarified. In this study,
      we investigated the effects of enzyme-untreated RJ (NRJ) and enzyme-treated RJ
      (ERJ) on the aging process focusing on motor functions, by using a genetically
      heterogeneous (HET) mouse model experimentally endowed with genetic diversity. We
      performed four different physical performance tests (grip strength, wire hang,
      horizontal bar, and rotarod). We showed that the age-related impairment of the
      motor functions was significantly delayed in RJ-treated mice. Both NRJ and ERJ
      were similarly effective against these types of aging-associated declines.
      Histological analyses revealed that the RJ treatment affected the muscle fiber
      size at an advanced age. We also demonstrated that age-related changes in muscle
      satellite cell markers and catabolic genes were affected in RJ-treated mice.
      These results suggest that non-protein components of RJ improved the motor
      function in aging mice. These findings indicate that RJ has the potential to
      change the QOL during aging by regulating the motor function.

PMID- 30200402
TI  - Porous Titanium Scaffolds Fabricated by Metal Injection Moulding for Biomedical
      Applications.
AB  - Biocompatible titanium scaffolds with up to 40% interconnected porosity were
      manufactured through the metal injection moulding process and the space holder
      technique. The mechanical properties of the manufactured scaffold showed a high
      level of compatibility with those of the cortical human bone. Sintering at 1250 
      degrees C produced scaffolds with 36% porosity and more than 90% interconnected
      pores, a compressive yield stress of 220 MPa and a Young's modulus of 7.80 GPa,
      all suitable for bone tissue engineering. Increasing the sintering temperature to
      1300  degrees C increased the Young's modulus to 22.0 GPa due to reduced
      porosity, while reducing the sintering temperature to 1150  degrees C lowered the
      yield stress to 120 MPa, indicative of insufficient sintering. Electrochemical
      studies revealed that samples sintered at 1150  degrees C have a higher corrosion
      rate compared with those at a sintering temperature of 1250  degrees C. Overall,
      it was concluded that sintering at 1250  degrees C yielded the most desirable
      results.

PMID- 30200403
TI  - Fatty Acid Profiles of Various Vegetable Oils and the Association between the Use
      of Palm Oil vs. Peanut Oil and Risk Factors for Non-Communicable Diseases in
      Yangon Region, Myanmar.
AB  - The majority of vegetable oils used in food preparation in Myanmar are imported
      and sold non-branded. Little is known about their fatty acid (FA) content. We
      aimed to investigate the FA composition of commonly used vegetable oils in the
      Yangon region, and the association between the use of palm oil vs. peanut oil and
      risk factors for non-communicable disease (NCD). A multistage cluster survey was
      conducted in 2016, and 128 oil samples from 114 households were collected. Data
      on NCD risk factors were obtained from a household-based survey in the same
      region, between 2013 and 2014. The oils most commonly sampled were non-branded
      peanut oil (43%) and non-branded palm oil (19%). Non-branded palm oil had a
      significantly higher content of saturated fatty acids (36.1 g/100 g) and a lower
      content of polyunsaturated fatty acids (9.3 g/100 g) than branded palm oil. No
      significant differences were observed regarding peanut oil. Among men, palm oil
      users had significantly lower mean fasting plasma glucose levels and mean BMI
      than peanut oil users. Among women, palm oil users had significantly higher mean
      diastolic blood pressure, and higher mean levels of total cholesterol and
      triglycerides, than peanut oil users. Regulation of the marketing of non-branded
      oils should be encouraged.

PMID- 30200404
TI  - Sex-Specific Human Milk Composition: The Role of Infant Sex in Determining Early
      Life Nutrition.
AB  - Male and female infants respond differentially to environmental stimuli, with
      different growth and neurodevelopmental trajectories. Male infants are more
      likely to be disadvantaged when subjected to adversity and show a higher risk of
      perinatal complications. However, the underlying causes of this sex-bias are not
      well defined and optimising the early life nutritional care may be necessary to
      minimise the "male disadvantage" that may be experienced early in life.
      Experimental models have demonstrated that animal milk composition differs
      according to offspring sex, suggesting that the tailoring of early life nutrition
      may be one mechanism to maximise health protection and development to infants of
      both sexes. However, evidence for a sex-specificity in human milk composition is
      limited and conflicting, with studies documenting higher milk energy content for
      either male or female infants. These data show sex differences, however, there
      has been limited compositional analysis of the current data nor strategies
      proposed for how sex-specific compositional differences in early life nutrition
      may be used to improve infant health. The present narrative review highlights
      that an improved understanding of sex-specific human milk composition is
      essential for promoting optimal infant growth and development.

PMID- 30200405
TI  - Obesity in Inflammatory Bowel Disease: Gains in Adiposity despite High Prevalence
      of Myopenia and Osteopenia.
AB  - BACKGROUND: Rising rates of obesity have been reported in patients with
      inflammatory bowel disease (IBD); however, prospective data is lacking. The aim
      of this study is to prospectively evaluate body composition in adults with IBD
      over 24 months. METHODS: Whole body dual energy X-ray absorptiometry (DXA) data
      was performed at 0 months, 12 months, and 24 months. Bone mineral density (BMD),
      fat mass index (FMI (kg)/height (m2)), appendicular skeletal muscle index (ASMI
      (kg)/height (m2)), visceral adipose tissue and the visceral adipose height index
      (VHI, VAT area (cm3)/height (m2)), and clinical and anthropometric assessments
      were performed at each time point. Multivariable linear mixed effects regression
      analyses were performed. RESULTS: Initially, 154 participants were assessed at
      baseline (70% Crohn's disease, 55% male, median age 31 years), of whom 129
      underwent repeated DXA at 12 months, and 110 underwent repeated DXA at 24 months.
      Amongst those undergoing repeated DXA, their body mass index (BMI) significantly
      increased over time, such that by 24 months, 62% of patients were overweight or
      obese (annual change BMI beta = 0.43, 95%CI = [0.18, 0.67], p = 0.0006). Gains in
      BMI related to increases in both FMI and VHI (beta = 0.33, 95%CI = [0.14, 0.53],
      p = 0.0007; beta = 0.08, 95%CI = [0.02, 0.13], p = 0.001; respectively), whereas
      ASMI decreased (beta = -0.07, 95%CI = [-0.12, -0.01], p = 0.01) with a concordant
      rise in rates of myopenia (OR = 3.1 95%CI = [1.2, 7.7]; p = 0.01). Rates of
      osteopenia and osteoporosis were high (37%), but remained unchanged over time (p
      = 0.23). CONCLUSION: Increasing rates of obesity in patients with IBD coincide
      with decreases in lean muscle mass over time, while high rates of osteopenia
      remain stable. These previously undocumented issues warrant attention in routine
      care to prevent avoidable morbidity.

PMID- 30200406
TI  - The Effectiveness and Cost-Effectiveness of Screening for and Vaccination Against
      Hepatitis B Virus among Migrants in the EU/EEA: A Systematic Review.
AB  - Migrants from hepatitis B virus (HBV) endemic countries to the European
      Union/European Economic Area (EU/EEA) comprise 5.1% of the total EU/EEA
      population but account for 25% of total chronic Hepatitis B (CHB) infection.
      Migrants from high HBV prevalence regions are at the highest risk for CHB
      morbidity. These migrants are at risk of late detection of CHB complications;
      mortality and onwards transmission. The aim of this systematic review is to
      evaluate the effectiveness and cost-effectiveness of CHB screening and
      vaccination programs among migrants to the EU/EEA. We found no RCTs or direct
      evidence evaluating the effectiveness of CHB screening on morbidity and mortality
      of migrants. We therefore used a systematic evidence chain approach to identify
      studies relevant to screening and prevention programs; testing, treatment, and
      vaccination. We identified four systematic reviews and five additional studies
      and guidelines that reported on screening and vaccination effectiveness. Studies
      reported that vaccination programs were highly effective at reducing the
      prevalence of CHB in children (RR 0.07 95% CI 0.04 to 0.13) following
      vaccination. Two meta-analyses of therapy for chronic HBV infection found
      improvement in clinical outcomes and intermediate markers of disease. We
      identified nine studies examining the cost-effectiveness of screening for CHB: a
      strategy of screening and treating CHB compared to no screening. The median
      acceptance of HB screening was 87.4% (range 32.3-100%). Multiple studies
      highlighted barriers to and the absence of effective strategies to ensure linkage
      of treatment and care for migrants with CHB. In conclusion, screening of high
      risk children and adults and vaccination of susceptible children, combined with
      treatment of CHB infection in migrants, are promising and cost-effective
      interventions, but linkage to treatment requires more attention.

PMID- 30200407
TI  - Euphosantianane A-D: Antiproliferative Premyrsinane Diterpenoids from the Endemic
      Egyptian Plant Euphorbia Sanctae-Catharinae.
AB  - Euphorbia species are rich in diterpenes. A solvent extraction of Euphorbia
      sanctae-catharinae, a species indigenous to the Southern Sinai of Egypt, afforded
      several premyrsinane diterpenoids (1-4) as well as previously reported
      metabolites (5-13) that included three flavonoids. Isolated compounds were
      chemically characterized by spectroscopic analysis. Identified compounds were
      bioassayed for anti-proliferative activity in vitro against colon (Caco-2) and
      lung (A549) tumor cell lines. Compound 9 exhibited robust anti-proliferative
      activity against A549 cells (IC50 = 3.3 uM). Absolute configurations for 8 versus
      9 were determined by experimental and TDDFT-calculated electronic circular
      dichorism (ECD) spectra.

PMID- 30200409
TI  - Design Method of Lightweight Metamaterials with Arbitrary Poisson's Ratio.
AB  - A heuristic approach to design lightweight metamaterials with novel
      configurations and arbitrary Poisson's ratio is studied by using the functional
      element topology optimization (FETO) method. Mathematical model of the
      optimization problem is established, where the minimization of the mass is set as
      the objective, then a series of metamaterials with Poisson's ratio ranging from 
      1.0 to +1.0 are designed by solving this model. The deformation resistance and
      vibration reduction performance of the novel metamaterials and conventional
      honeycomb are compared by numerical simulations. Specific stiffness analysis
      shows that the novel metamaterials are 5.6 to 21.0 times more resistant to
      deformation than that of the honeycomb, and frequency response shows about 60%
      improvement in vibration reduction performance. Finally, the lightweight effects
      of the novel metamaterials on deformation resistance and vibration reduction
      performance are analyzed, and further analysis reflects that the lightweight
      effects increase with the increase of the absolute value of the Poisson's ratio.

PMID- 30200411
TI  - The Formation of Polyvinylidene Fluoride Membranes with Tailored Properties via
      Vapour/Non-Solvent Induced Phase Separation.
AB  - The present investigation reports as it is possible to prepared polyvinylidene
      fluoride (PVDF) membranes for microfiltration (MF) and ultrafiltration (UF)
      applications, by using triethyl phosphate (TEP) as non-toxic solvent in
      accordance with the Green Chemistry. Casting solutions containing different
      concentrations of polyethylene glycol (PEG) were prepared in order to study its
      effect on the final membrane morphology and properties. The possibility to finely
      modulate membrane properties was also investigated by applying two different
      membrane preparation techniques, the Non-Solvent Induced Phase Separation (NIPS)
      and its coupling with Vapour Induced Phase Separation (VIPS). Membranes'
      morphology was detected by Scanning Electron Microscopy (SEM). Thickness,
      porosity, contact angle, pore size and water permeability were also recorded.
      Both the PEG content in the dope solution and the selected time intervals during
      which the nascent films were exposed to established relative humidity and
      temperature were found to play a crucial role in membrane formation. In
      particular, it was demonstrated as, by varying PEG content between 10 and 20 wt
      %, and by setting the exposure time to humidity at 0/2.5/5/7.5 min, membranes
      with different pore diameter and bicontinuous structure, suitable for UF and MF
      applications, could be easily obtained.

PMID- 30200408
TI  - Muscle Loss in Chronic Liver Diseases: The Example of Nonalcoholic Liver Disease.
AB  - Recent publications highlight a frequent loss of muscle mass in chronic liver
      diseases, including nonalcoholic fatty liver disease (NAFLD), and its association
      with a poorer prognosis. In NAFLD, given the role of muscle in energy metabolism,
      muscle loss promotes disease progression. However, liver damage may be directly
      responsible of this muscle loss. Indeed, muscle homeostasis depends on the
      balance between peripheral availability and action of anabolic effectors and
      catabolic signals. Moreover, insulin resistance of protein metabolism only
      partially explains muscle loss during NAFLD. Interestingly, some data indicate
      specific alterations in the liver-muscle axis, particularly in situations such as
      excess fructose/sucrose consumption, associated with increased hepatic de novo
      lipogenesis (DNL) and endoplasmic reticulum stress. In this context, the liver
      will be responsible for a decrease in the peripheral availability of anabolic
      factors such as hormones and amino acids, and for the production of catabolic
      effectors such as various hepatokines, methylglyoxal, and uric acid. A better
      understanding of these liver-muscle interactions could open new therapeutic
      opportunities for the management of NAFLD patients.

PMID- 30200412
TI  - Implementation of the International Classification of Functioning, Disability,
      and Health (ICF) Core Sets for Children and Youth with Cerebral Palsy: Global
      Initiatives Promoting Optimal Functioning.
AB  - Background: The International Classification of Functioning, Disability, and
      Health (ICF) Core Sets for children and youth with cerebral palsy (CP) offer
      service providers and stakeholders a specific framework to explore functioning
      and disability for assessment, treatment, evaluation, and policy purposes in a
      global context. Objective: Describe global initiatives applying the ICF Core Sets
      for children and youth with CP, with a focus on contributions to clinical
      practice and challenges in their implementation. Methods: This is a descriptive
      cross-sectional study. Ongoing initiatives applying the ICF Core Sets for CP in
      Russia, Poland, Malawi, and Brazil are included. Results: The main contributions
      of applying the ICF Core Sets for children and youth with CP include: (1) an
      objective description of abilities and limitations in everyday activities; (2) a
      consistent identification of facilitators and barriers influencing functioning;
      (3) a practical communication tool promoting client-centered care and
      multidisciplinary teamwork; and, (4) a useful guideline for measurement
      selection. The main challenges of adopting the ICF Core Sets are related to lack
      of ICF knowledge requiring intense training and translating results from
      standardized measures into the ICF qualifiers in a consistent way. Conclusions:
      Global initiatives include research and clinical applications at the program,
      service and system levels. The ICF Core Sets for CP are useful tools to guide
      service provision and build profiles of functioning and disability. Global
      interprofessional collaboration, capacity training, and informatics (e-records)
      will maximize their applications and accelerate adoption.

PMID- 30200413
TI  - Submerged Osmotic Processes: Design and Operation to Mitigate Mass Transfer
      Limitations.
AB  - Submerged forward osmosis (FO) is of high interest for bioreactors, such as
      osmotic membrane bioreactor, microalgae photobioreactor, food or bioproduct
      concentration where pumping through pressurized modules is a limitation due to
      viscosity or breakage of fragile components. However, so far, most FO efforts
      have been put towards cross flow configurations. This study provides, for the
      first time, insights on mass transfer limitations in the operation of submerged
      osmotic systems and offer recommendations for optimized design and operation. It
      is demonstrated that operation of the submerged plate and frame FO module
      requires draw circulation in the vacuum mode (vacuum assisted osmosis) that is in
      favor of the permeation flux. However, high pressure drops and dead zones
      occurring in classical U-shape FO draw channel strongly disadvantage this design;
      straight channel design proves to be more effective. External concentration
      polarization (ECP) is also a crucial element in the submerged FO process since
      mixing of the feed solution is not as optimized as in the cross flow module
      unless applying intense stirring. Among the mitigation techniques tested, air
      scouring proves to be more efficient than feed solution circulation. However, ECP
      mitigation methodology has to be adapted to application specificities with
      regards to combined/synergetic effects with fouling mitigation.

PMID- 30200415
TI  - Broadband Spectra and Efficient Laser Performance of a Disordered
      Nd:Sr0.7La0.3Mg0.3Al11.7O19 Crystal.
AB  - Here, we demonstrate the broadband spectra and efficient laser performance of a
      disordered Nd:Sr0.7La0.3Mg0.3Al11.7O19 (Nd:ASL) crystal. The polarized absorption
      and emission spectra were characterized and calculated with the Judd-Ofelt (J-O)
      theory, and the results show that this crystal has relatively large sigma
      polarized absorption and emission cross sections, with peak emission cross
      sections of 4.5 * 10-20 cm2 at 1051 nm and an emission width of 30 nm at 1074 nm,
      which are favorable for pulsed lasers. The laser-diode-pumped continuous-wave
      (CW) and passively Q-switched lasers at 1051 nm were realized for the first time
      to our best knowledge. For CW laser, the maximum output power was 1.95 W with the
      slope efficiency of 42.6%, and for the passive Q-switching, the maximum output
      power was 0.73 W with the pulse width of 7.96 ns and peak power of 5.64 W. The
      results demonstrate that Nd:ASL crystal is a potential candidate for lasers,
      especially high-peak pulsed lasers such as Q-switching and mode-locking.

PMID- 30200414
TI  - Wnt Effector TCF4 Is Dispensable for Wnt Signaling in Human Cancer Cells.
AB  - T-cell factor 4 (TCF4), together with beta-catenin coactivator, functions as the
      major transcriptional mediator of the canonical wingless/integrated (Wnt)
      signaling pathway in the intestinal epithelium. The pathway activity is essential
      for both intestinal homeostasis and tumorigenesis. To date, several mouse models
      and cellular systems have been used to analyze TCF4 function. However, some
      findings were conflicting, especially those that were related to the defects
      observed in the mouse gastrointestinal tract after Tcf4 gene deletion, or to a
      potential tumor suppressive role of the gene in intestinal cancer cells or
      tumors. Here, we present the results obtained using a newly generated conditional
      Tcf4 allele that allows inactivation of all potential Tcf4 isoforms in the mouse
      tissue or small intestinal and colon organoids. We also employed the clustered
      regularly interspaced short palindromic repeats (CRISPR)/Cas9 system to disrupt
      the TCF4 gene in human cells. We showed that in adult mice, epithelial expression
      of Tcf4 is indispensable for cell proliferation and tumor initiation. However, in
      human cells, the TCF4 role is redundant with the related T-cell factor 1 (TCF1)
      and lymphoid enhancer-binding factor 1 (LEF1) transcription factors.

PMID- 30200410
TI  - Chemical Composition and Biological Activities of Essential Oils of Curcuma
      Species.
AB  - Members of the genus Curcuma L. have been used in traditional medicine for
      centuries for treating gastrointestinal disorders, pain, inflammatory conditions,
      wounds, and for cancer prevention and antiaging, among others. Many of the
      biological activities of Curcuma species can be attributed to nonvolatile
      curcuminoids, but these plants also produce volatile chemicals. Essential oils,
      in general, have shown numerous beneficial effects for health maintenance and
      treatment of diseases. Essential oils from Curcuma spp., particularly C. longa,
      have demonstrated various health-related biological activities and several
      essential oil companies have recently marketed Curcuma oils. This review
      summarizes the volatile components of various Curcuma species, the biological
      activities of Curcuma essential oils, and potential safety concerns of Curcuma
      essential oils and their components.

PMID- 30200416
TI  - Atomic Scale Simulation on the Fracture Mechanism of Black Phosphorus Monolayer
      under Indentation.
AB  - Molecular dynamics simulations on the indentation process of freestanding and
      Pt(111)-supported black phosphorus (BP) monolayer were conducted to study the
      fracture mechanism of the membrane. For the freestanding BP monolayer, crack
      grows firstly along armchair direction and then zigzag direction during the
      indentation process. Whereas, for the Pt(111)-supported BP monolayer, crack
      growth shows no obvious directionality, with irregular distribution of crack
      tips. Further study on stress distribution shows that maximum normal stress
      component at elastic stage is in zigzag direction for the freestanding BP
      monolayer, and in vertical direction for the Pt(111)-supported BP monolayer. As
      BP monolayer is remarkably anisotropic for in-plane mechanical properties and
      homogeneous for out-of-plane mechanical properties, the difference of stress
      state may be a key reason for the different fracture behavior in these two cases.
      These findings may help to understand the failure mechanism of BP, when applied
      in nano-devices.

PMID- 30200417
TI  - Quiescence in Aedes aegypti: Interpopulation Differences Contribute to Population
      Dynamics and Vectorial Capacity.
AB  - The strategy of Aedes aegypti to prolong embryonic viability by quiescence has
      severe implications for geographic expansion and maintenance of mosquito
      populations in areas under control measures. We evaluated the effects of
      quiescence on biological parameters directly or indirectly associated with
      population dynamics and vectorial capacity in populations of this mosquito
      species from two Brazilian municipalities characterized as dengue, chikungunya,
      and Zika transmission areas. Egg viability, initial hatching time, post-embryonic
      development time, adult emergence rate, sexual proportion, adult size, fecundity,
      and fertility were analyzed using eggs stored for 10, 40, 70, 100, 130, and 160
      d. Quiescence time reduced overall egg viability and post-embryonic development
      time in both municipalities but was more costly in Aracaju (100 d, 8 d) than in
      Recife (130 d, 7.5 d). Emergence rates increased in Recife when the eggs were
      older, but not in Aracaju. Significant deviations in sexual proportion, with male
      predominance, were observed in both populations. Initial hatch, fecundity,
      fertility, and adult size did not significantly influence egg quiescence time.
      These results indicate intrinsic and differential characteristics for each A.
      aegypti population, suggesting a differential cost of quiescence for population
      dynamics parameters that can indirectly affect vectorial capacity and control
      measures.

PMID- 30200418
TI  - Nanosecond Laser Fabrication of Hydrophobic Stainless Steel Surfaces: The Impact
      on Microstructure and Corrosion Resistance.
AB  - Creation of hydrophobic and superhydrophobic surfaces has attracted broad
      attention as a promising solution for protection of metal surfaces from corrosive
      environments. This work investigates the capability of nanosecond fiber laser
      surface texturing followed by a low energy coating in the fabrication of
      hydrophobic 17-4 PH stainless steel surfaces as an alternative to the ultrashort
      lasers previously utilized for hydrophobic surfaces production. Laser texturing
      of the surface followed by applying the hydrophobic coating resulted in steady
      state contact angles of up to 145 degrees , while the non-textured coated base
      metal exhibited the contact angle of 121 degrees . The microstructure and
      compositional analysis results confirmed that the laser texturing process neither
      affects the microstructure of the base metal nor causes elemental loss from the
      melted regions during the ultrafast melting process. However, the electrochemical
      measurements demonstrated that the water-repelling property of the surface did
      not contribute to the anticorrosion capability of the substrate. The resultant
      higher corrosion current density, lower corrosion potential, and higher corrosion
      rate of the laser textured surfaces were ascribed to the size of fabricated
      surface micro-grooves, which cannot retain the entrapped air inside the
      hierarchical structure when fully immersed in a corrosive medium, thus degrading
      the material's corrosion performance.

PMID- 30200419
TI  - Tunable Multipolar Fano Resonances and Electric Field Enhancements in Au Ring
      Disk Plasmonic Nanostructures.
AB  - We theoretically research the characteristics of tunable multipolar Fano
      resonances in novel-designed Au ring-disk plasmonic nanostructures. We
      systematically study some structural parameters that influence the multipolar
      Fano resonances of the nanostructures. Adjustment of the radius (R1 and R2) of
      the Au ring, the radius (R3) of the Au disk and the thickness (H) of the Au ring
      disk can effectively adjust the multipolar Fano resonances. The complex field
      distributions excited by a Au ring-disk can produce dark resonance modes. At the
      frequency of the multipolar Fano resonances, strong localized field distributions
      can be obtained. The Fano resonances exhibit strong light-extinction properties
      in Au ring-disk nanostructures, which can be applied to an optical tunable filter
      and optical switch.

PMID- 30200420
TI  - Heated Intraperitoneal Chemotherapy in the Management of Advanced Ovarian Cancer.
AB  - Heated intraperitoneal chemotherapy (HIPEC) has several potential benefits.
      Higher doses of chemotherapy can be used with HIPEC because the plasma-peritoneal
      barrier results in little absorption into the blood stream. HIPEC offers higher
      peritoneal penetration in comparison to an intravenous (IV) regimen and does not
      have the traditional normothermic intraperitoneal (IP) regimen limitation of post
      operative adhesions. Hyperthermia itself has cytotoxic effects and can potentiate
      antineoplastic effects of chemotherapy in part by increasing the depth of tumor
      penetration by up to 3 mm. For the treatment of ovarian cancer, HIPEC has been
      evaluated in the recurrent setting with secondary cytoreduction. Recent studies,
      including a prospective trial, have evaluated its role in primary management of
      ovarian cancer. This review summarizes previous and ongoing studies regarding the
      use of HIPEC in the management of ovarian cancer.

PMID- 30200421
TI  - Plasma 25-Hydroxy Vitamin D Is Not Associated with Either Cognitive Function or
      Academic Performance in Adolescents.
AB  - Several observational studies have reported an association between low levels of
      vitamin D (VD) and poor cognition in adults, but there is a paucity of data on
      such an association in adolescents. We investigated the association between VD
      and cognitive function or academic achievement among 1370 adolescents, who were
      selected from public middle schools in Kuwait, using stratified multistage
      cluster random sampling with probability proportional to size. Plasma 25-hydroxy
      VD (25-OH-D) was measured using liquid chromatography-tandem mass spectrometry
      (LC-MS/MS). An age-adjusted standard score (ASC), calculated from Raven's
      Standard Progressive Matrices test, was used to evaluate cognitive function;
      academic achievements were extracted from the schools' records. Data on various
      covariates were collected from the parents through a self-administered
      questionnaire and from the adolescents using face-to-face interviews. 25-OH-D was
      weakly correlated positively with ASC (rho = 0.06; p = 0.04). Univariable linear
      regression analysis showed an association between 25-OH-D categories and ASC
      after adjusting for gender, but adjusting for parental education was sufficient
      to explain this association. Multivariable analysis showed no association between
      25-OH-D and ASC after adjusting for potential confounders whether 25-OH-D was
      fitted as a continuous variable (p = 0.73), a variable that is categorized by
      acceptable cutoff points (p = 0.48), or categorized into quartiles (p = 0.88).
      Similarly, 25-OH-D was not associated with academic performance. We conclude that
      25-OH-D is associated with neither cognitive function nor academic performance in
      adolescents.

PMID- 30200422
TI  - Metabolically Healthy versus Unhealthy Morbidly Obese: Chronic Inflammation,
      Nitro-Oxidative Stress, and Insulin Resistance.
AB  - Metabolically heathy obesity is characterised by the presence of obesity in the
      absence of metabolic disturbances. The aim of our study was to analyse pro
      inflammatory, nitro-oxidative stress, and insulin-resistance (IR) markers in
      metabolically healthy morbidly obese (MHMO) with respect to metabolically
      unhealthy morbidly obese (MUHMO) with metabolic syndrome (MS) and to identify the
      potential predictors of MS in the MHMO group. Two groups of MHMO and MUHMO with
      MS were analysed. We evaluated serum high sensitivity C reactive protein (hsCRP),
      tumor necrosis factor alpha (TNF-alpha), chemerin, nitrite and nitrate (NOx),
      total oxidant status (TOS), total antioxidant response (TAR), fasting blood
      glucose, insulin, and homeostasis model assessment of insulin resistance (HOMA
      IR.) MHMO have similar hsCRP and TNF-alpha values as the MUHMO with MS, while
      chemerin was significantly lower in MHMO. NOx was higher in MUHMO with MS
      patients, while no difference regarding TOS and TAR was found between the two
      groups. HOMA-IR and insulin values were lower in MHMO as compared to the MUHMO
      with MS group. Insulin, HOMA-IR, and chemerin were identified predictors of MS in
      MHMO. In conclusion, MHMO and MUHMO display similarities and differences in terms
      of chronic inflammation, nitro-oxidative stress, and IR. Markers of IR and
      chemerin are possible predictors of MS in MHMO.

PMID- 30200423
TI  - Measuring Children's Sodium and Potassium Intakes in NZ: A Pilot Study.
AB  - Low sodium and high potassium intakes in childhood protect against rises in blood
      pressure (BP) and risk of cardiovascular disease (CVD) later in life. Our aim was
      to pilot methods for collection of 24-h urine samples (gold standard) and diet
      recalls to assess sodium and potassium intakes and their food sources in 30
      children aged 8-11 years at one New Zealand primary school. A diverse sample (n =
      27) was recruited over a two-week period. All children provided a urine sample
      (71% complete) and interviewer-assisted 24-h diet recall (Intake24 software).
      Median (range) sodium intake was 2191 (1087 to 4786) mg/day (salt equivalent 5.5
      g), potassium intake was 1776 (800-2981) mg/day, BP was 105 (84-129)/62 (53-89)
      mmHg, and sodium to potassium molar ratio was 2.0 (1.1-4.8). Frequent use of
      discretionary salt was uncommon. Major food sources of sodium were bread, pies
      and pastries, and bread and pasta-based dishes, and potassium were sauces and
      condiments, dairy products, and non-alcoholic beverages. Most participants
      provided adequate data and enjoyed taking part. A larger survey is warranted to
      confirm findings and inform a potential intervention(s). Small improvements to
      study procedures and resources should improve completeness of urine samples and
      quality of 24-h diet recall data.

PMID- 30200424
TI  - Breakfast in the United States: Food and Nutrient Intakes in Relation to Diet
      Quality in National Health and Examination Survey 2011-2014. A Study from the
      International Breakfast Research Initiative.
AB  - The contribution of breakfast to diet quality (DQ) can inform future dietary
      guidelines. This study examined breakfast nutrition in relation to overall DQ,
      using dietary data from the first reported day of the National Health and
      Examination Survey (NHANES) 2011-2014 (n = 14,488). Relative DQ was assessed
      using the Nutrient Rich Foods Index (NRF9.3) and the USDA Healthy Eating Index
      2015 (HEI 2015). The sample was stratified by NRF9.3 tertiles and by age and
      socioeconomic groups. Four out of 5 NHANES participants had breakfast on the day
      of the interview. Breakfast provided 19-22% of dietary energy depending on age.
      Breakfast intakes of complex carbohydrates and total sugars were proportionately
      higher and intakes of protein and fats were lower relative to breakfast energy
      intakes. Breakfast provided more that 20% of daily intakes of B vitamins,
      vitamins A and D, folate, calcium, iron, potassium and magnesium. Eating
      breakfast was associated with higher NRF9.3 DQ scores. Breakfasts associated with
      the top tertile of NRF9.3 scores had less added sugars and fats than those
      associated with the bottom tertile. Such breakfasts had more fruit and juices,
      more whole grain products, more milk and yogurt and less meat and eggs. Breakfast
      patterns and food choices that favored fruit, whole grains and dairy were
      associated with healthiest diets.

PMID- 30200425
TI  - Wine and Olive Oil Phenolic Compounds Interaction in Humans.
AB  - Extra virgin olive oil (EVOO) and red wine (RW) are two basic elements that form
      part of the so-called Mediterranean diet. Both stand out because of their high
      phenolic compound content and their potential related health benefits. The
      present study is focused on the metabolic disposition of resveratrol (RESV),
      tyrosol (TYR), and hydroxytyrosol (HT) following the consumption of EVOO, RW, and
      a combination of both. In this study, 12 healthy volunteers consumed a single
      dose of 25 mL of EVOO, 150 mL of RW, and a combination of both in a crossover
      randomized clinical trial. Urinary recovery of RESV, TYR, and HT was analysed in
      urine samples collected over a 6-h period following the intake of each treatment.
      Higher HT levels were observed following EVOO compared to RW (3788 +/- 1751 nmols
      and 2308 +/- 847 nmols respectively). After the combination of EVOO and RW, the
      recovery of TYR and HT metabolites increased statistically compared to their
      separate consumption (4925 +/- 1751 nmols of TYR and 6286 +/- 3198 nmols of HT).
      EVOO triggered an increase in glucuronide conjugates, while RW intake raised
      sulfate metabolites. Marginal effects were observed in RESV increased
      bioavailability after the combination of RW with the fat matrix provided by EVOO.

PMID- 30200427
TI  - Petromylidenes A-C: 2-Alkylidene Bile Salt Derivatives Isolated from Sea Lamprey
      (Petromyzon marinus).
AB  - Three novel bile acid derivatives, petromylidenes A-C (1-3), featuring uncommon
      alkylidene adductive scaffolds, were isolated from water conditioned with
      sexually mature male sea lampreys (Petromyzon marinus). Their structures were
      elucidated by mass spectrometry and NMR spectroscopy, and by comparison to
      spectral data of related structures. The identification of compounds 1-3, further
      illustrates the structural diversity of the 5alpha bile salt family. Compounds 1
      3 exhibited notable biological properties as well, including high olfactory
      potencies in adult sea lampreys and strong behavioral attraction of ovulated
      female sea lampreys. Electro-olfactogram recordings indicated that the limit of
      detection for 1 was 10-9 M, 2 was 10-11 M, and 3 was less than 10-13 M. These
      results suggested 1-3 were likely male pheromones, which guide reproductive
      behaviors in the sea lamprey.

PMID- 30200426
TI  - Enterohemorrhagic E. coli (EHEC)-Secreted Serine Protease EspP Stimulates
      Electrogenic Ion Transport in Human Colonoid Monolayers.
AB  - One of the characteristic manifestations of Shiga-toxin-producing Escherichia
      coli (E. coli) infection in humans, including EHEC and Enteroaggregative E. coli
      O104:H4, is watery diarrhea. However, neither Shiga toxin nor numerous components
      of the type-3 secretion system have been found to independently elicit fluid
      secretion. We used the adult stem-cell-derived human colonoid monolayers (HCM) to
      test whether EHEC-secreted extracellular serine protease P (EspP), a member of
      the serine protease family broadly expressed by diarrheagenic E. coli can act as
      an enterotoxin. We applied the Ussing chamber/voltage clamp technique to
      determine whether EspP stimulates electrogenic ion transport indicated by a
      change in short-circuit current (Isc). EspP stimulates Isc in HCM. The EspP
      stimulated Isc does not require protease activity, is not cystic fibrosis
      transmembrane conductance regulator (CFTR)-mediated, but is partially Ca2+
      dependent. EspP neutralization with a specific antibody reduces its potency in
      stimulating Isc. Serine Protease A, secreted by Enteroaggregative E. coli, also
      stimulates Isc in HCM, but this current is CFTR-dependent. In conclusion, EspP
      stimulates colonic CFTR-independent active ion transport and may be involved in
      the pathophysiology of EHEC diarrhea. Serine protease toxins from E. coli
      pathogens appear to serve as enterotoxins, potentially significantly contributing
      to watery diarrhea.

PMID- 30200428
TI  - A Feasibility Study of Processing Polydimethylsiloxane-Sodium
      Carboxymethylcellulose Composites by a Low-Cost Fused Deposition Modeling 3D
      Printer.
AB  - Additive manufacturing (AM) techniques allow the construction of complex physical
      models reproducing the content of a specific CAD file, and, among them, Fused
      Deposition Molding (FDM) stands out for its many advantages. The aim of the
      present work is to perform a feasibility study of 3D printing of a model of human
      heart to be used to simulate surgical operations or for training through a two
      step method based on extrusion and FDM processes. To this purpose, typical
      extrusion instrumentation and a simple and low-cost FDM printer are employed, in
      combination with a thermoplastic polydimethylsiloxane (PDMS), chosen for its
      transparency, flexibility, and high resistance to multiple agents and aging. To
      improve its tactile properties and mimic the slimy effect of living organs,
      sodium carboxymethylcellulose (Na-CMC) fibrils are added to it. The starting
      materials, the neat PDMS filament and the composite one, are deeply characterized
      in terms of structural, thermal, and rheological properties in order to fix the
      most suitable extrusion and FDM parameters. The composite filaments show larger
      diameter and roughness, which cause undesirable effects during 3D printing, such
      as episodic nozzle obstruction, and exhibit a faster degradation, making the FDM
      step difficult. Nevertheless, the major issues are related to the low
      crystallinity degree of the employed polymer. The feasibility study carried out
      leads to the printing of composite layers, even though far from the desired final
      target. Possible solutions to print the fully characterized Na-CMC/PDMS composite
      are addressed in the conclusion of this work.

PMID- 30200429
TI  - Previous Interspecific Courtship Impairs Female Receptivity to Conspecifics in
      the Parasitoid Wasp Nasonia longicornis But Not in N. vitripennis.
AB  - Interspecific sexual interactions are not uncommon in animals. In sympatry,
      females often face the risk of accidentally mating with a heterospecific male.
      Based on the actual risks imposed by the environment at a given time and place,
      females should be able to adjust their mate acceptance in order to avoid
      interspecific copulations as well as accidentally refusing to mate with a
      conspecific. We investigate the ability of females of the two parasitoid wasp
      species Nasonia vitripennis (Nv) and N. longicornis (Nl) to adjust their mate
      acceptance in response to previous unsuccessful courtship by heterospecific
      males. We show that Nl females are more reluctant to mate with a conspecific male
      when having been courted previously by a heterospecific male, but Nv females are
      not. We argue that this strategy is reasonable for Nl females but not for Nv
      females, which follow a different strategy to avoid the fitness costs imposed by
      heterospecific copulations.

PMID- 30200432
TI  - Metabolaid(r) Combination of Lemon Verbena and Hibiscus Flower Extract Prevents
      High-Fat Diet-Induced Obesity through AMP-Activated Protein Kinase Activation.
AB  - Lemon verbena (Lippia citriodora) has been used as a food spice, cosmetic, and in
      traditional medicine formulations to treat asthma and diabetes in South America
      and Southern Europe. Hibiscus flower (Hibiscus sabdariffa L.) is used in
      traditional Chinese medicine in the form of a tea to treat hypertension and
      inflammation. In the present study, we examined the synergistic effects of a
      formula of Metabolaid(r) (MetA), a combination of lemon verbena and hibiscus
      flower extracts, on obesity and its complications in high-fat-diet (HFD)-induced
      obese mice. The results showed that MetA decreased body weight, white adipose
      tissue (WAT), and liver weight. Additionally, serum and hepatic lipid profiles,
      glucose levels, glucose tolerance, and cold-induced thermogenesis were
      significantly improved. Appetite-regulating hormones adiponectin and leptin were
      significantly increased and decreased, respectively, while the inflammatory
      related factors tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 were
      downregulated by MetA. Adipogenesis-activating gene expression was decreased,
      while increased thermogenesis-inducing genes were upregulated in the WAT,
      correlating with increased phosphorylation of AMPK and fatty-acid oxidation in
      the liver. Taken together, these results suggest that MetA decreased obesity and
      its complications in HFD mice. Therefore, this formula may be a candidate for the
      prevention and treatment of obesity and its complications.

PMID- 30200433
TI  - A Study of the Effects of Al, Cr, Hf, and Ti Additions on the Microstructure and
      Oxidation of Nb-24Ti-18Si Silicide Based Alloys.
AB  - In Nb-silicide based alloys Al, Cr, Hf, and Ti additions are crucial for
      achieving balance of properties. It is not known how the simultaneous addition of
      Hf with Al and Ti, or Hf with Al, Cr, and Ti affects macrosegregation, and how
      the alloying affects hardness, Young's modulus and bulk alloy oxidation, and
      contamination of the solid solution Nbss and the Nb5Si3 compound by oxygen. Two
      alloys with nominal compositions (at.%) Nb-24Ti-18Si-5Al-5Hf (alloy NbSiTiHf-5Al)
      and Nb-24Ti-18Si-5Al-5Cr-5Hf (alloy NbSiTiHf-5Al-5Cr) were studied in the as-cast
      and heat-treated conditions and after isothermal oxidation at 800 and 1200 
      degrees C and were compared with similar alloys without Hf. In both alloys there
      was macrosegregation of Si and Ti, which was more severe in NbSiTiHf-5Al. Both
      alloys formed Nbss+betaNb5Si3 eutectic. The Nbss was stable and its Al and Cr
      concentrations increased with increasing Ti concentration. In both conditions the
      betaNb5Si3 was observed in the alloys NbSiTiHf-5Al and NbSiTiHf-5Al-5Cr, and the
      gammaNb5Si3 only in the alloy NbSiTiHf-5Al. In both heat-treated alloys, separate
      Hf-rich Nb5Si3 grains were formed. The Si and Al concentrations in Nb5Si3
      respectively decreased and increased with increasing Ti concentration. Al and Cr
      had a stronger hardening effect in the Nbss than Al, Cr, and Hf. Al, Cr, and Ti
      had a stronger negative effect on the Young's modulus of the Nbss compared with
      Al, Cr, Hf, and Ti. When Nb was substituted by Ti, Cr, and Hf, and Si by Al in
      the betaNb5Si3, the Young's modulus was reduced compared with the unalloyed
      silicide. At 800  degrees C both alloys did not exhibit catastrophic pest
      oxidation after 100 h. The Nbss and Nb5Si3 were contaminated by oxygen in both
      alloys, the former more severely. At 1200  degrees C the scales spalled-off, more
      severely in the alloy NbSiTiHf-5Al, where substrate that was heavily contaminated
      by oxygen below the scale also spalled-off. In both alloys the contamination of
      Nb5Si3 and Nbss by oxygen was more severe compared with 800  degrees C, but the
      silicides were not contaminated by oxygen in their bulk. The Nbss was not
      contaminated by oxygen only in the bulk of the alloy NbSiTiHf-5Al-5Cr.

PMID- 30200430
TI  - Selenium, Selenoproteins, and Immunity.
AB  - Selenium is an essential micronutrient that plays a crucial role in development
      and a wide variety of physiological processes including effect immune responses.
      The immune system relies on adequate dietary selenium intake and this nutrient
      exerts its biological effects mostly through its incorporation into
      selenoproteins. The selenoproteome contains 25 members in humans that exhibit a
      wide variety of functions. The development of high-throughput omic approaches and
      novel bioinformatics tools has led to new insights regarding the effects of
      selenium and selenoproteins in human immuno-biology. Equally important are the
      innovative experimental systems that have emerged to interrogate molecular
      mechanisms underlying those effects. This review presents a summary of the
      current understanding of the role of selenium and selenoproteins in regulating
      immune cell functions and how dysregulation of these processes may lead to
      inflammation or immune-related diseases.

PMID- 30200431
TI  - Challenges in the Diagnosis of Magnesium Status.
AB  - Magnesium is a critical mineral in the human body and is involved in ~80% of
      known metabolic functions. It is currently estimated that 60% of adults do not
      achieve the average dietary intake (ADI) and 45% of Americans are magnesium
      deficient, a condition associated with disease states like hypertension,
      diabetes, and neurological disorders, to name a few. Magnesium deficiency can be
      attributed to common dietary practices, medications, and farming techniques,
      along with estimates that the mineral content of vegetables has declined by as
      much as 80-90% in the last 100 years. However, despite this mineral's importance,
      it is poorly understood from several standpoints, not the least of which is its
      unique mechanism of absorption and sensitive compartmental handling in the body,
      making the determination of magnesium status difficult. The reliance on several
      popular sample assays has contributed to a great deal of confusion in the
      literature. This review will discuss causes of magnesium deficiency, absorption,
      handling, and compartmentalization in the body, highlighting the challenges this
      creates in determining magnesium status in both clinical and research settings.

PMID- 30200434
TI  - Green Tea, Coffee, and Caffeine Consumption Are Inversely Associated with Self
      Report Lifetime Depression in the Korean Population.
AB  - This study investigated the associations of green tea, coffee, and caffeine
      consumption with self-report lifetime depression in the Korean population using
      data from the Korean National Health and Nutrition Examination Survey. In total,
      9576 participants (3852 men and 5724 women) aged 19 years or older were selected
      for the present study. Green tea, coffee, and caffeine consumption levels were
      assessed with a validated food frequency questionnaire. Multivariate logistic
      regression analysis was used to determine the odds ratios (OR) and 95% confidence
      intervals (CIs) for depression according to green tea, coffee, and caffeine
      consumption. Frequent green tea consumers (>=3 cups/week) had 21% lower
      prevalence of depression (OR = 0.79, 95% CI = 0.63-0.99, p for trend = 0.0101)
      than green tea non-consumers after adjustment for potential confounders.
      Likewise, frequent coffee drinkers (>=2 cups/day) had 32% lower prevalence of
      depression (OR = 0.68, 95% CI = 0.55-0.85, p for trend = 0.0026) than coffee non
      drinkers after adjustment for potential confounders. Also, participants in the
      highest quartile of caffeine consumption had 24% lower prevalence of depression
      than those in the lowest quartile (OR = 0.76, 95% CI = 0.62-0.92, p for trend =
      0.0032). Frequent consumption of green tea, coffee, or caffeine was associated
      with a reduced prevalence of self-report lifetime depression in Korean adults. A
      prospective study and randomized clinical trials should be conducted to confirm
      the inverse relationships of green tea and coffee consumption with risk of
      depression.

PMID- 30200435
TI  - Transcriptomic Profiling and Gene Disruption Revealed that Two Genes Related to
      PUFAs/DHA Biosynthesis May be Essential for Cell Growth of Aurantiochytrium sp.
AB  - Aurantiochytrium sp. PKU#SW7 is a thraustochytrid strain that was found to
      exhibit high potential for docosahexaenoic acid (DHA, C22:6n-3) production. In
      this work, the transcriptome of Aurantiochytrium sp. PKU#SW7 was analyzed for the
      study of genes involved in basic metabolic functions and especially in the
      mechanisms of DHA biosynthesis. Sequence annotation and functional analysis
      revealed that the strain contains components of fatty acid synthesis (FAS) and
      polyketide synthase (PKS) pathways. Fatty acid desaturases and elongases were
      identified as components of FAS pathway, whilst key components of PKS pathway
      were also found in the cDNA library. The relative contribution of the two
      pathways to the synthesis of DHA was unknown, as both pathways appeared to be
      lacking full complement of genes for standalone synthesis of DHA. Further
      analysis of two putative genes encoding the very-long-chain (3R)-3-hydroxyacyl
      CoA dehydratase and dehydrase/isomerase involved in FAS and PKS pathways,
      respectively, revealed that under various salinity conditions, their relative
      expression levels changed corresponding to the variation of DHA content in
      Aurantiochytrium sp. Independent knock outs of these genes in Aurantiochytrium
      sp. resulted in poor cell growth, probably due to little or no intracellular DHA
      accumulation. Hence, it can be speculated that both genes are engaged in DHA
      biosynthesis and DHA in Aurantiochytrium sp. could be produced by jointed actions
      of both FAS and PKS systems.

PMID- 30200437
TI  - Knockdown of Butyrylcholinesterase but Not Inhibition by Chlorpyrifos Alters
      Early Differentiation Mechanisms in Human Neural Stem Cells.
AB  - Butyrylcholinesterase (BChE) is the evolutionary counterpart to
      acetylcholinesterase (AChE). Both are expressed early in nervous system
      development prior to cholinergic synapse formation. The organophosphate pesticide
      chlorpyrifos (CPF) primarily exerts toxicity through the inhibition of AChE,
      which results in excess cholinergic stimulation at the synapse. We hypothesized
      that the inhibition of AChE and BChE by CPF may impair early neurogenesis in
      neural stem cells (NSCs). To model neurodevelopment in vitro, we used human NSCs
      derived from induced pluripotent stem cells (iPSCs) with a focus on the initial
      differentiation mechanisms. Over the six days of NSC differentiation, the BChE
      activity and mRNA expression significantly increased, while the AChE activity and
      expression remained unchanged. The CPF treatment (10 MUM) caused 82% and 92%
      inhibition of AChE and BChE, respectively. The CPF exposure had no effect on the
      cell viability or the expression of the differentiation markers HES5, DCX, or
      MAP2. However, the shRNA-knockdown of the BChE expression resulted in the
      decreased or delayed expression of the transcription factors HES5 and HES3. BChE
      may have a role in the differentiation of NSCs independent of, or in addition to,
      its enzymatic activity.

PMID- 30200438
TI  - Immune-Enhancement and Anti-Inflammatory Activities of Fatty Acids Extracted from
      Halocynthia aurantium Tunic in RAW264.7 Cells.
AB  - Halocynthia aurantium, an edible ascidian species, has not been studied
      scientifically, even though tunicates and ascidians are well-known to contain
      several unique and biologically active materials. The current study investigated
      the fatty acid profiles of the H. aurantium tunic and its immune-regulatory
      effects on RAW264.7 macrophage cells. Results of the fatty acid profile analysis
      showed a difference in ratios, depending on the fatty acids being analysed,
      including those of saturated fatty acids (SFA), monounsaturated fatty acids
      (MUFA), and polyunsaturated fatty acids (PUFA). In particular, omega-3 fatty
      acids, such as eicosatrienoic acid n-3 (ETA n-3), eicosapentaenoic acid (EPA),
      and docosahexaenoic acid (DHA), were much higher than omega-6 fatty acids.
      Moreover, the H. aurantium tunic fatty acids, significantly and dose-dependently,
      increased the NO and prostaglandin E2 (PGE2) production in RAW264.7 cells, for
      immune-enhancement without cytotoxicity. In addition, these fatty acids regulated
      the transcription of immune-associated genes, including iNOS, IL-1beta, IL-6, COX
      2, and TNF-alpha. These actions were activated and deactivated via Mitogen
      activated protein kinase (MAPK)and NF-kappaB signaling, to regulate the immune
      responses. Conversely, the H. aurantium tunic fatty acids effectively suppressed
      the inflammatory cytokine expressions, including iNOS, IL-1beta, IL-6, COX-2, and
      TNF-alpha, in LPS-stimulated RAW264.7 cells. Productions of COX-2 and PGE2, which
      are key biomarkers for inflammation, were also significantly reduced. These
      results elucidated the immune-enhancement and anti-inflammatory mechanisms of the
      H. aurantium tunic fatty acids in macrophage cells. Moreover, the H. aurantium
      tunic might be a potential fatty acid source for immune-modulation.

PMID- 30200439
TI  - Multidimensionality of Health Inequalities: A Cross-Country Identification of
      Health Clusters through Multivariate Classification Techniques.
AB  - Despite major efforts in scientific literature to explain and understand the
      social determinants of health inequalities, the complex association between
      social causes and health outcomes remains empirically questionable and
      theoretically puzzling. To date, the studies on social determinants of health has
      mainly been generated by research techniques and methods that were developed to
      answer specific questions about the causes and effects of particular indicators
      on specific health outcomes. The present exploratory study follows a complex
      system approach to capture the interdependence between socioeconomic status,
      lifestyles, and health in a single measure that enables international comparisons
      of population health. Specifically, this study is aimed to: (a) classify
      individuals' state of health according the usage of multidimensional data on
      physical and mental health, SES, lifestyles and risk behaviors, in order to (b)
      compare the relative strength of the different predictors of health groups (or
      clusters) at the individual-level and, finally, (c) to measure the level of
      health inequalities between different countries. From a complex system approach,
      this study uses multivariate classification methods to compare health groups in a
      sample of 29 countries and shows that interdependence models may be useful to
      describe and compare between-country health inequalities that are not visible
      through techniques for the analysis of dependence. The present work offers two
      fundamental contributions. On the one hand, this study compares the relative
      relevance of different indicators that are susceptible to affect individual
      health outcomes; on the other hand, the resulting multidimensional classification
      of countries according health clusters provides an alternative for inter-country
      health comparisons.

PMID- 30200440
TI  - Demineralized Bone Matrix Coating Si-Ca-P Ceramic Does Not Improve the
      Osseointegration of the Scaffold.
AB  - The aim of this study was to manufacture and evaluate the effect of a biphasic
      calcium silicophosphate (CSP) scaffold ceramic, coated with a natural
      demineralized bone matrix (DBM), to evaluate the efficiency of this novel ceramic
      material in bone regeneration. The DBM-coated CSP ceramic was made by coating a
      CSP scaffold with gel DBM, produced by the partial sintering of different-sized
      porous granules. These scaffolds were used to reconstruct defects in rabbit
      tibiae, where CSP scaffolds acted as the control material. Micro-CT and
      histological analyses were performed to evaluate new bone formation at 1, 3, and
      5 months post-surgery. The present research results showed a correlation among
      the data obtained by micro-CT and the histomorphological results, the gradual
      disintegration of the biomaterial, and the presence of free scaffold fragments
      dispersed inside the medullary cavity occupied by hematopoietic bone marrow over
      the 5-month study period. No difference was found between the DBM-coated and
      uncoated implants. The new bone tissue inside the implants increased with
      implantation time. Slightly less new bone formation was observed in the DBM
      coated samples, but it was not statistically significant. Both the DBM-coated and
      the CSP scaffolds gave excellent bone tissue responses and good
      osteoconductivity.

PMID- 30200441
TI  - Ball Milling's Effect on Pine Milled Wood Lignin's Structure and Molar Mass.
AB  - The effect of ball milling expressed as the yield of milled wood lignin (MWL) on
      the structure and molar mass of crude milled wood lignin (MWLc) preparation is
      studied to better understand the process' fundamentals and find optimal
      conditions for MWL isolation (i.e., to obtain the most representative sample with
      minimal degradation). Softwood (loblolly pine) MWLc preparations with yields of
      20-75% have been isolated and characterized based on their molar mass
      distribution (by Size Exclusion Chromatography (SEC)), hydroxyl groups of
      different types (31P NMR), methoxyl groups (HS-ID GC-MS), and sugar composition
      (based on methanolysis). Classical MWL purification is not used to access the
      whole extracted lignin. The results indicate that lignin degradation during ball
      milling occurs predominantly in the high molar mass fraction and is less
      pronounced in the low molar mass fraction. This results in a significant decrease
      in the Mz and Mw of the extracted MWLc with an increase in the yield of MWLc, but
      has only a very subtle effect on the lignin structure if the yield of MWLc is
      kept below about 55%. Therefore, no tedious optimization of process variables is
      necessary to achieve the required MWLc yield in this range for structural studies
      of softwood MWL. The sugar composition shows higher amounts of pectin components
      in MWLs of low yields and higher amounts of glucan and mannan in high-yield MWLs,
      confirming that lignin extraction starts from the middle lamella in the earlier
      stages of MWL isolation, followed by lignin extraction from the secondary wall
      region.

PMID- 30200436
TI  - The p53 Pathway in Glioblastoma.
AB  - The tumor suppressor and transcription factor p53 plays critical roles in tumor
      prevention by orchestrating a wide variety of cellular responses, including
      damaged cell apoptosis, maintenance of genomic stability, inhibition of
      angiogenesis, and regulation of cell metabolism and tumor microenvironment. TP53
      is one of the most commonly deregulated genes in cancer. The p53-ARF-MDM2 pathway
      is deregulated in 84% of glioblastoma (GBM) patients and 94% of GBM cell lines.
      Deregulated p53 pathway components have been implicated in GBM cell invasion,
      migration, proliferation, evasion of apoptosis, and cancer cell stemness. These
      pathway components are also regulated by various microRNAs and long non-coding
      RNAs. TP53 mutations in GBM are mostly point mutations that lead to a high
      expression of a gain of function (GOF) oncogenic variants of the p53 protein.
      These relatively understudied GOF p53 mutants promote GBM malignancy, possibly by
      acting as transcription factors on a set of genes other than those regulated by
      wild type p53. Their expression correlates with worse prognosis, highlighting
      their potential importance as markers and targets for GBM therapy. Understanding
      mutant p53 functions led to the development of novel approaches to restore p53
      activity or promote mutant p53 degradation for future GBM therapies.

PMID- 30200442
TI  - Anti-Atopic Properties of Gracillin Isolated from Dioscorea quinqueloba on 2,4
      Dinitrochlorobenzene-Induced Skin Lesions in Mice.
AB  - Naturally occurring saponins have been reported to have anti-inflammatory and
      immunomodulatory effects. However, the effects of gracillin, a main saponin
      component of Dioscorea quinqueloba (D. quinqueloba), on atopic dermatitis (AD),
      have not been previously studied. The aim of this study was to determine whether
      gracillin isolated from D. quinqueloba has an anti-AD effect on 2,4
      dinitrochlorobenzene (DNCB)-induced AD-like skin lesions in SKH-1 hairless mice.
      Topical co-treatment of gracillin and DNCB for two weeks markedly reduced
      symptoms typical of AD (redness, itching, swelling and skin lichenification),
      decreased transepidermal water loss (TEWL) and increased skin hydration. In
      addition, gracillin strongly inhibited PI-induced IL-4 expression in RBL-2H3
      cells and in the skins of AD mice. Our results suggest gracillin is a potential
      candidate for the prevention and treatment of AD and other inflammatory skin
      disorders.

PMID- 30200443
TI  - Native V. californicum Alkaloid Combinations Induce Differential Inhibition of
      Sonic Hedgehog Signaling.
AB  - Veratrum californicum is a rich source of steroidal alkaloids such as
      cyclopamine, a known inhibitor of the Hedgehog (Hh) signaling pathway. Here we
      provide a detailed analysis of the alkaloid composition of V. californicum by
      plant part through quantitative analysis of cyclopamine, veratramine, muldamine
      and isorubijervine in the leaf, stem and root/rhizome of the plant. To determine
      whether additional alkaloids in the extracts contribute to Hh signaling
      inhibition, the concentrations of these four alkaloids present in extracts were
      replicated using commercially available standards, followed by comparison of
      extracts to alkaloid standard mixtures for inhibition of Hh signaling using Shh
      Light II cells. Alkaloid combinations enhanced Hh signaling pathway antagonism
      compared to cyclopamine alone, and significant differences were observed in the
      Hh pathway inhibition between the stem and root/rhizome extracts and their
      corresponding alkaloid standard mixtures, indicating that additional alkaloids
      present in these extracts are capable of inhibiting Hh signaling.

PMID- 30200444
TI  - Eating Disorders in Relationship with Dietary Habits among Pharmacy Students in
      Romania.
AB  - Changing dietary habits of university students is due to personal, social,
      educational or religious factors. The relationship between dietary habits and
      presence of eating disorders among university students is less known in Romania.
      Material and Methods: Ninety-one pharmacy students (91.21% women) were included
      in the research. Socio-demographic, anthropometric, medical, and psychological
      data were collected. Dietary self-declared habits were registered. The analysis
      of data was done using SPSS, v23. Results: A total of 69.2% of students had
      normal weight, 64.84% preferred to have lunch, and 23.08% eat during nights. The
      majority of subjects (95.6%), stated that they eat snacks daily. More than one
      third of students keep diets to reduce their weight. Younger students tend to eat
      more main meals per week, snack more, and eat later after getting up in the
      morning. Subjects with high body dissatisfaction tended to have fewer main meals
      (r = -0.265, p = 0.011) and to skip breakfasts (-0.235, p = 0.025) and dinners (r
      = -0.303, p < 0.001). Pharmacy students that presented higher rate of emotional
      problems tend to sleep less and skip breakfast. Conclusions: Female pharmacy
      students had higher mean scores on all subscales than those found among Romanian
      women. A strong relationship between dietary habits and eating disorders was
      identified.

PMID- 30200445
TI  - Cross-Cultural Adaptation, Validity, and Reproducibility of the Mediterranean
      Islands Study Food Frequency Questionnaire in the Elderly Population Living in
      the Spanish Mediterranean.
AB  - The objective of this study was to perform cross-cultural adaptation of the
      Mediterranean Islands Study Food Frequency Questionnaire (MEDIS-FFQ) and to
      evaluate its reproducibility and validity in a population over 60 years of age in
      the Spanish Mediterranean. Three hundred forty-one people completed the food
      frequency questionnaire (FFQ), which was administered twice (FFQ1 and FFQ2) with
      nine 24-h dietary recalls (24-HDRs) over a nine-month period to assess its
      reproducibility and validity. Cross-cultural translation and adaptation were
      performed according to the International Society for Pharmacoeconomics and
      Outcomes Research (ISPOR) guidelines and included direct translation, back
      translation, and a pilot comprehension test. Reproducibility was evaluated with
      Pearson's and interclass correlation coefficients. Validity was estimated using
      correlations between the FFQ food groups and the 24-HDR mean. The levels of
      agreement and misclassification were expressed as the proportions of individuals
      classified by comparing the estimated information from the FFQ2 and the 24-HDR.
      Reproducibility correlation coefficients ranged from r = 0.44 to r = 0.90.
      Validity indices ranged from 0.71 to 0.99. More than 80% of the subjects were
      classified in the same quartile on both instruments. The kappa statistic showed a
      moderate to high level of agreement (0.70-0.95) between the two instruments. In
      conclusion, the MEDIS-FFQ showed good reproducibility and validity in estimating
      the nutrient intake of the elderly population in the Spanish Mediterranean.

PMID- 30200446
TI  - Does Physical Fitness Affect Academic Achievement among Japanese Adolescents? A
      Hybrid Approach for Decomposing Within-Person and Between-Persons Effects.
AB  - Positive association between physical fitness and academic achievement in
      adolescents has been suggested yet the causal effect of physical fitness on
      academic achievement remains unclear. This study examined if longitudinal changes
      in physical fitness were associated with changes in academic achievement among
      junior high school students. Analyses were based on a two-year with three time
      point data of 567 students (aged 12-13 years old at the baseline-point; 303 boys)
      who entered in five Japanese junior high schools in 2015. Academic achievement
      was evaluated using the student's overall grade point average. Comprehensive
      physical fitness score was summed up from eight fitness tests: 50-m sprint,
      standing broad jump, repeated side-steps, sit and reach, sit-ups, hand-grip
      strength, handball throw, and 20-m shuttle run or endurance run. The hybrid
      regression model was applied to examine the impact of change in physical fitness
      on change in academic achievement using multiple imputation to account for non
      response at follow-up. The changes in fitness score within-person and the
      differences in average of fitness score of three-time points between-person were
      associated with change in overall grade point average for boys. No significant
      association between fitness score and overall grade point average was observed in
      girls. Opportunities for increased physical fitness may be important to support
      academic achievement, particularly in junior high school boys.

PMID- 30200448
TI  - Food Safety Analysis Using Electrochemical Biosensors.
AB  - Rapid and precise analytical tools are essential for monitoring food safety and
      screening of any undesirable contaminants, allergens, or pathogens, which may
      cause significant health risks upon consumption. Substantial developments in
      analytical techniques have empowered the analyses and quantitation of these
      contaminants. However, conventional techniques are limited by delayed analysis
      times, expensive and laborious sample preparation, and the necessity for highly
      trained workers. Therefore, prompt advances in electrochemical biosensors have
      supported significant gains in quantitative detection and screening of food
      contaminants and showed incredible potential as a means of defying such
      limitations. Apart from indicating high specificity towards the target analytes,
      these biosensors have also addressed the challenge of food industry by providing
      high analytical accuracy within complex food matrices. Here, we discuss some of
      the recent advances in this area and analyze the role and contributions made by
      electrochemical biosensors in the food industry. This article also reviews the
      key challenges we believe biosensors need to overcome to become the industry
      standard.

PMID- 30200447
TI  - One-Step Acidic Hydrothermal Preparation of Dendritic Rutile TiO2 Nanorods for
      Photocatalytic Performance.
AB  - Three-dimensional and dendritic rutile TiO2 nanorods were successfully fabricated
      on a Ti foil surface using a one-step acidic hydrothermal method. The TiO2
      nanorods were characterized using X-ray diffraction (XRD), energy dispersive X
      ray spectrometry (EDX), transmission electron microscopy (TEM), scanning electron
      microscopy (SEM), and optical contact angle testing. The results showed that the
      nanorods with diameters of 100-500 nm and lengths of 100 nm to 1 MUm were
      obtained on the Ti foil surface. The length and density of the TiO2 nanorods were
      perfect at the conditions of HCl concentration 0.5 mol/L, temperature 220 
      degrees C, and reaction time 12 h. The TiO2 nanorods formed parallel to the
      consumption of Ti and grew along the (110) direction having a tetragonal rutile
      crystal. The morphology of the nanorods possessed a three-dimensional structure.
      The contact angle of the nanorods was only 13 +/- 3.1 degrees . Meanwhile, the
      photocatalytic activities of the TiO2 nanorods were carried out using ultraviolet
      fluorescence spectrophotometry for the methyl orange detection, and the
      degradation was found to be about 71.00% +/- 2.43%. Thus, TiO2 nanorods can be
      developed by a one-step acidic hydrothermal method using Ti foil simultaneously
      as the substrate with a TiO2 source; the TiO2 nanorods exhibited photocatalytic
      performance while being environment-friendly.

PMID- 30200449
TI  - Attitudes and Recommendations of Physicians towards Alcohol Consumption and
      Cardiovascular Health: A Perspective from Argentina.
AB  - Despite epidemiological findings of improvements in cardiovascular risk factors
      with a light-to-moderate intake of alcohol, many misconceptions remain regarding
      alcohol intake and the risks and benefits of consumption. We sought to examine
      physician attitudes and recommendations regarding alcohol intake in a cohort of
      Argentine physicians and to establish their sources of knowledge. An online
      national survey was distributed through the Argentine Federation of Cardiology
      (FAC) to cardiologists, internal medicine specialists, general and other
      subspecialty physicians in Argentina. The survey was completed by 745 physicians,
      of whom 671 (90%) were cardiologists. In total, 35% of physicians viewed moderate
      alcohol intake to be beneficial for cardiovascular health, 36% believed only wine
      offered such benefits, 24% viewed any intake to be harmful, and 5% had other
      opinions. More than half (57%) self-reported their knowledge came from academic
      sources. Regarding knowledge of drinking guidelines, only 41% of physicians were
      aware of the concept of "standard drink". Physicians were generally not
      comfortable converting standard drinks into other metric units, however men
      tended to be more comfortable than women (p = 0.052). Physicians were not
      satisfied with their knowledge of drinking guidelines (3.01 +/- 2.73, on a 0-10
      scale). Physicians were generally comfortable in counselling patients regarding
      safe limits of consumption (6.22 +/- 3.20, on a 0-10 scale). Argentine physicians
      were not satisfied with their knowledge of alcohol consumption guidelines or
      their understanding of the reported metrics. Only one-third of study participants
      viewed moderate alcohol intake as beneficial for cardiovascular health. This
      study shows the necessity to optimize the sources of knowledge.

PMID- 30200450
TI  - The Use of Orientation Templates and Free-Hand Implant Insertion in Artificial
      Mandibles-An Experimental Laboratory Examination in Fifth-Year Dental Students.
AB  - Implant dentistry is a growing field in the education of undergraduate dental
      students. The present laboratory study evaluates factors which may potentially
      influence the accuracy of free-hand implant insertion and the use of an
      orientation template. After three-dimensional planning using coDiagnostiXTM,
      orientation templates, including sleeves for the pilot-drill in regions 41 and
      45, were manufactured by thermoforming. Sixty-one fifth year dental students
      inserted one implant using the orientation template and another implant free-hand
      in an artificial mandible. Information regarding age, sex, handedness, education,
      and the time required for implant insertion were recorded. Subsequently, the
      mandibles were scanned using cone-beam-computed tomography and the accuracy of
      the implant position was assessed, while statistical analysis followed. The free
      hand implant insertion resulted in a distal deviation of -1.34 +/- 5.15 degrees 
      and a mesial mismatch of 0.06 +/- 0.79 mm at the artificial bone level compared
      to the sleeves. When using the orientation templates, the deviation decreased to 
      0.67 +/- 3.48 degrees  and a distal mismatch of -0.22 +/- 0.62 mm was achieved.
      The difference was statistically significant for the mismatch (p < 0.049).
      Regarding the limitations of our study, it could be said that the accuracy level
      achieved by dental undergraduates using implant placement with orientation
      templates is comparable to that in other studies.

PMID- 30200451
TI  - Preparation of Nickel Nanoparticles by Direct Current Arc Discharge Method and
      Their Catalytic Application in Hybrid Na-Air Battery.
AB  - Nickel nanoparticles were prepared by the arc discharge method. Argon and
      argon/hydrogen mixtures were used as plasma gas; the evaporation of anode
      material chiefly resulted in the formation of different arc-anode attachments at
      different hydrogen concentrations. The concentration of hydrogen was fixed at 0,
      30, and 50 vol% in argon arc, corresponding to diffuse, multiple, and constricted
      arc-anode attachments, respectively, which were observed by using a high-speed
      camera. The images of the cathode and anode jets were observed with a suitable
      band-pass filter. The relationship between the area change of the cathode/anode
      jet and the synchronous voltage/current waveform was studied. By investigating
      diverse arc-anode attachments, the effect of hydrogen concentration on the
      features of nickel nanoparticles were investigated, finding that 50 vol% H2
      concentration has high productivity, fine crystallinity, and appropriate size
      distribution. The synthesized nickel nanoparticles were then used as catalysts in
      a hybrid sodium-air battery. Compared with commercial a silver nanoparticle
      catalyst and carbon black, nickel nanoparticles have better electrocatalytic
      performance. The promising electrocatalytic activity of nickel nanoparticles can
      be ascribed to their good crystallinity, effective activation sites, and Ni/NiO
      composite structures. Nickel nanoparticles prepared by the direct current (DC)
      arc discharge method have the potential to be applied as catalysts on a large
      scale.

PMID- 30200454
TI  - Metabolic Syndrome and the Risk of Breast Cancer and Subtypes by Race, Menopause
      and BMI.
AB  - The objective of this study was to investigate the association of metabolic
      syndrome (MetS) with the risk of invasive breast cancer and molecular subtypes
      across race, menopause, and body mass index (BMI) groups. We examined the
      association of metabolic syndrome and its components with risk of invasive breast
      cancer among 94,555 female participants of the National Institute of Health
      American Association of Retired Persons (NIH-AARP) Diet and Health Study,
      accounting for ductal carcinoma in situ as a competing risk. Cox proportional
      hazard regression with the Fine and Gray method was used to generate hazard
      ratios (HR) and 95% confidence intervals (CI) adjusting for baseline
      sociodemographic, behavioral, and clinical covariates. During a mean follow-up of
      14 years, 5380 (5.7%) women developed breast cancer. Overall, MetS at baseline
      was associated with a 13% increased risk of breast cancer compared to women
      without MetS (HR: 1.13, 95% CI: 1.00, 1.27); similar estimates were obtained
      among postmenopausal women (HR: 1.14, 95% CI: 1.01, 1.29). MetS was associated
      with a slight but non-significantly increased risk of breast cancer among those
      with both normal weight and overweight/obesity, and those with estrogen receptor
      positive breast cancer subtype. In the NIH-AARP cohort, MetS was associated with
      an increased risk of breast cancer. Further studies are needed to definitively
      evaluate the association of MetS with triple negative breast cancer subtypes
      across all levels of BMI.

PMID- 30200452
TI  - Cardiotoxicity of Uremic Toxins: A Driver of Cardiorenal Syndrome.
AB  - Cardiovascular disease (CVD) is highly prevalent in the setting of chronic kidney
      disease (CKD). Such coexistence of CVD and CKD-the so-called "cardiorenal or
      renocardiac syndrome"-contributes to exponentially increased risk of
      cardiovascular (CV) mortality. Uremic cardiomyopathy is a characteristic cardiac
      pathology commonly found in CKD. CKD patients are also predisposed to heart
      rhythm disorders especially atrial fibrillation. Traditional CV risk factors as
      well as known CKD-associated CV risk factors such as anemia are insufficient to
      explain CV complications in the CKD population. Accumulation of uremic retention
      solutes is a hallmark of impaired renal excretory function. Many of them have
      been considered inert solutes until their biological toxicity is unraveled and
      they become accepted as "uremic toxins". Direct cardiotoxicity of uremic toxins
      has been increasingly demonstrated in recent years. This review offers a
      mechanistic insight into the pathological cardiac remodeling and dysfunction
      contributed by uremic toxins with a main focus on fibroblastic growth factor-23,
      an emerging toxin playing a central role in the chronic kidney disease-mineral
      bone disorder, and the two most investigated non-dialyzable protein-bound uremic
      toxins, indoxyl sulfate and p-cresyl sulfate. Potential therapeutic strategies
      that could address these toxins and their relevant mediated pathways since pre
      dialysis stages are also discussed.

PMID- 30200455
TI  - A Novel Strategy for Creating Tissue-Engineered Biomimetic Blood Vessels Using 3D
      Bioprinting Technology.
AB  - In this work, a novel strategy was developed to fabricate prevascularized cell
      layer blood vessels in thick tissues and small-diameter blood vessel substitutes
      using three-dimensional (3D) bioprinting technology. These thick vascularized
      tissues were comprised of cells, a decellularized extracellular matrix (dECM),
      and a vasculature of multilevel sizes and multibranch architectures. Pluronic
      F127 (PF 127) was used as a sacrificial material for the formation of the
      vasculature through a multi-nozzle 3D bioprinting system. After printing,
      Pluronic F127 was removed to obtain multilevel hollow channels for the attachment
      of human umbilical vein endothelial cells (HUVECs). To reconstruct functional
      small-diameter blood vessel substitutes, a supporting scaffold (SE1700) with a
      double-layer circular structure was first bioprinted. Human aortic vascular
      smooth muscle cells (HA-VSMCs), HUVECs, and human dermal fibroblasts-neonatal
      (HDF-n) were separately used to form the media, intima, and adventitia through
      perfusion into the corresponding location of the supporting scaffold. In
      particular, the dECM was used as the matrix of the small-diameter blood vessel
      substitutes. After culture in vitro for 48 h, fluorescent images revealed that
      cells maintained their viability and that the samples maintained structural
      integrity. In addition, we analyzed the mechanical properties of the printed
      scaffold and found that its elastic modulus approximated that of the natural
      aorta. These findings demonstrate the feasibility of fabricating different kinds
      of vessels to imitate the structure and function of the human vascular system
      using 3D bioprinting technology.

PMID- 30200453
TI  - Rare Genetic Diseases with Defects in DNA Repair: Opportunities and Challenges in
      Orphan Drug Development for Targeted Cancer Therapy.
AB  - A better understanding of mechanistic insights into genes and enzymes implicated
      in rare diseases provide a unique opportunity for orphan drug development.
      Advances made in identification of synthetic lethal relationships between rare
      disorder genes with oncogenes and tumor suppressor genes have brought in new
      anticancer therapeutic opportunities. Additionally, the rapid development of
      small molecule inhibitors against enzymes that participate in DNA damage response
      and repair has been a successful strategy for targeted cancer therapeutics. Here,
      we discuss the recent advances in our understanding of how many rare disease
      genes participate in promoting genome stability. We also summarize the latest
      developments in exploiting rare diseases to uncover new biological mechanisms and
      identify new synthetic lethal interactions for anticancer drug discovery that are
      in various stages of preclinical and clinical studies.

PMID- 30200456
TI  - Health and Nutrition Studies Related to Cereal Biodiversity: A Participatory
      Multi-Actor Literature Review Approach.
AB  - Recently, a large and growing body of literature has investigated the health
      potential of different wheat species. In particular, a considerable number of
      studies dealing with nutritional aspects has grown up around the theme of the
      recovery of ancient wheat varieties (species that have remained unchanged over
      the last hundred years). According to several studies, indeed, ancient varieties
      present a healthier nutritional profile than modern ones. In the framework of the
      European project "CERERE, CEreal REnaissance in Rural Europe: embedding diversity
      in organic and low-input food systems", this paper aimed to review recent
      research on the issue of health and nutritional cereal systems by adopting an
      innovative and participatory multi-actor approach which involved practitioners
      along with researchers. The participatory approach is the main innovation and
      peculiarity of this literature review. Nevertheless, the review highlights the
      many positive effects derived from eating whole and ancient grains such as a
      significant reduction in the risk of chronic diseases such as cancer,
      cardiovascular disease, and also a more favorable long-term weight management and
      increase in satiety. This review may be considered as a fruitful starting point
      that integrates research results to foster current and future healthier and
      sustainable practices in cereal systems.

PMID- 30200457
TI  - K2S2O8-Promoted Aryl Thioamides Synthesis from Aryl Aldehydes Using Thiourea as
      the Sulfur Source.
AB  - Thiourea as a sulfur atom transfer reagent was applied for the synthesis of aryl
      thioamides through a three-component coupling reaction with aryl aldehydes and
      N,N-dimethylformamide (DMF) or N,N-dimethylacetamide (DMAC). The reaction could
      tolerate various functional groups and gave moderate to good yields of desired
      products under the transition-metal-free condition.

PMID- 30200458
TI  - High-Frequency Occurrence of Surfactin Monomethyl Isoforms in the Ferment Broth
      of a Bacillus subtilis Strain Revealed by Ion Trap Mass Spectrometry.
AB  - Surfactins are cyclic lipopeptides consisting of a beta-hydroxy fatty acid of
      various chain length and a peptide ring of seven amino acids linked together by a
      lactone bridge, forming the cyclic structure of the peptide chain. These
      compounds are produced mainly by Bacillus species and possess numerous biological
      effects such as antimicrobial (antiviral, antibacterial, and antifungal)
      activities. A mixture of surfactins extracted from Bacillus subtilis strain SZMC
      6179J was examined by HPLC-ESI-IT-MS technique, enhancing their separation to
      reveal novel lipopeptide varieties with higher masses and to characterize their
      structures. During the MS2 spectra analyses of their sodiated molecular ions [M +
      Na]+, a previously rarely encountered group of surfactins was detected and two
      novel types of the group were discovered containing methyl esterified aspartic
      acid residue in their fifth amino acid position. The relative amounts of these
      monomethyl isoforms exceeded 35% of the produced surfactin in total. In the m/z
      value of 1114, all the detected isoforms possessed aspartic acid 4-methyl ester
      residue in their fifth amino acid position (C17-[Lxx4, AME5], C18-[AME5]),
      offering an opportunity to separate a pure fraction of the compound and to study
      its biological activities in the future.

PMID- 30200459
TI  - SrCe0.9Sm0.1O3-alpha Compounded with NaCl-KCl as a Composite Electrolyte for
      Intermediate Temperature Fuel Cell.
AB  - SrCeO3 and SrCe0.9Sm0.1O3-alpha were synthesized using a high-temperature solid
      state reaction method using Sm2O3, SrCO3, CeO2 as precursors, then the
      SrCe0.9Sm0.1O3-alpha-NaCl-KCl composite electrolyte was fabricated by compounding
      SrCe0.9Sm0.1O3-alpha with NaCl-KCl and sintering it at a lower temperature (750 
      degrees C) than that of a single SrCeO3 material (1540  degrees C). The phase and
      microstructure of the samples were characterized by X-ray diffraction (XRD) and
      scanning electron microscopy (SEM). The conductivities of the samples were
      measured in dry nitrogen atmosphere using electrochemical analyzer. The
      conductivities of the SrCeO3, SrCe0.9Sm0.1O3-alpha and SrCe0.9Sm0.1O3-alpha-NaCl
      KCl at 700  degrees C were 2.09 * 10-5 S.cm-1, 1.82 * 10-3 S.cm-1 and 1.43 * 10-1
      S.cm-1 respectively. The conductivities of SrCe0.9Sm0.1O3-alpha-NaCl-KCl
      composite electrolyte are four orders of magnitude higher than those of SrCeO3
      and two orders of magnitude higher than those of SrCe0.9Sm0.1O3-alpha. The result
      of logsigma ~ logpO2 plot indicates that SrCe0.9Sm0.1O3-alpha-NaCl-KCl is almost
      a pure ionic conductor. The electrolyte resistance and the polarization
      resistance of the H2/O2 fuel cell based on SrCe0.9Sm0.1O3-alpha-NaCl-KCl
      composite electrolyte under open-circuit condition were 1.0 Omega.cm2 and 0.2
      Omega.cm2 respectively. Further, the obtained maximum power density at 700 
      degrees C was 182 mW.cm-2.

PMID- 30200460
TI  - Gender Differences and Comorbidities in U.S. Adults with Bipolar Disorder.
AB  - BACKGROUND: Past studies have evaluated the association of various comorbidities
      with bipolar disorder. This study analyzes differences in the prevalence and
      association of medical and psychiatric comorbidities in bipolar patients by
      gender. METHODS: A retrospective analysis was conducted using the Nationwide
      Inpatient Sample (2010-2014). Using International Classification of Diseases, 9th
      Revision, Clinical Modification (ICD-9-CM) codes, we narrowed the study
      population to comprise those with a primary diagnosis of bipolar disorder and
      then obtained information about comorbidities. The differences in comorbidities
      by gender were quantified using chi-square tests and the logistic regression
      model (odds ratio (OR)). RESULTS: Hypertension (20.5%), asthma (12.5%) and
      hypothyroidism (8.1%) were the top medical comorbidities found in bipolar
      patients. Migraine and hypothyroidism were seen three times higher in females (OR
      = 3.074 and OR = 3.001; respectively). Females with bipolar disorder had higher
      odds of comorbid inflammatory disorders like asthma (OR = 1.755), Crohn's disease
      (OR = 1.197) and multiple sclerosis (OR = 2.440) compared to males. Females had a
      two-fold higher likelihood of comorbid post-traumatic stress disorder (PTSD) (OR
      = 2.253) followed by personality disorders (OR = 1.692) and anxiety disorders (OR
      = 1.663) compared to males. CONCLUSION: Women with bipolar disorder have a much
      higher medical comorbidity burden than men and may highly benefit from an
      integrated team of physicians to manage their condition and improve their health
      related quality of life.

PMID- 30200462
TI  - Low-Temperature Spark Plasma Sintering of ZrW2-xMoxO8 Exhibiting Controllable
      Negative Thermal Expansion.
AB  - Molybdenum-doped zirconium tungstate (ZrW2-xMoxO8) has been widely studied
      because of its large isotropic coefficient of negative thermal expansion (NTE).
      However, low density and poor sinterability limit its production and application.
      In this study, relative density greater than 90% single-phase ZrW2-xMoxO8 (0.0 <=
      x <= 1.0) sintered bodies were fabricated by spark plasma sintering (500-600 
      degrees C for 10 min) using ZrW2-xMoxO7(OH)2.2H2O precursor powders as the
      starting material. High-temperature X-ray diffraction and thermomechanical
      analysis were used to investigate the change in the order-disorder phase
      transition temperature of the sintered materials; it gradually dropped from 170 
      degrees C at x = 0.0 to 78  degrees C at x = 0.5, and then to below room
      temperature at x >= 0.7. In addition, all sintered bodies exhibited NTE behavior.
      The NTE coefficient was controllable by changing the x value as follows: from 
      7.85 * 10-6  degrees C-1 (x = 0) to -9.01 * 10-6  degrees C-1 (x = 0.6) and from 
      3.22 * 10-6  degrees C-1 (x = 0) to -2.50 * 10-6  degrees C-1 (x = 1.0) before
      and after the phase transition, respectively. Rietveld structure refinement
      results indicate that the change in the NTE coefficient can be straightforwardly
      traced to the thermodynamic instability of the terminal oxygen atoms, which only
      have one coordination.

PMID- 30200461
TI  - Interaction of 2'R-ochratoxin A with Serum Albumins: Binding Site, Effects of
      Site Markers, Thermodynamics, Species Differences of Albumin-binding, and
      Influence of Albumin on Its Toxicity in MDCK Cells.
AB  - Ochratoxin A (OTA) is a nephrotoxic mycotoxin. Roasting of OTA-contaminated
      coffee results in the formation of 2'R-ochratoxin A (2'R-OTA), which appears in
      the blood of coffee drinkers. Human serum albumin (HSA) binds 2'R-OTA (and OTA)
      with high affinity; therefore, albumin may influence the tissue uptake and
      elimination of ochratoxins. We aimed to investigate the binding site of 2'R-OTA
      (verses OTA) in HSA and the displacing effects of site markers to explore which
      molecules can interfere with its albumin-binding. Affinity of 2'R-OTA toward
      albumins from various species (human, bovine, porcine and rat) was tested to
      evaluate the interspecies differences regarding 2'R-OTA-albumin interaction.
      Thermodynamic studies were performed to give a deeper insight into the molecular
      background of the complex formation. Besides fluorescence spectroscopic and
      modeling studies, effects of HSA, and fetal bovine serum on the cytotoxicity of
      2'R-OTA and OTA were tested in MDCK kidney cell line in order to demonstrate the
      influence of albumin-binding on the cellular uptake of ochratoxins. Site markers
      displaced more effectively 2'R-OTA than OTA from HSA. Fluorescence and binding
      constants of 2'R-OTA-albumin and OTA-albumin complexes showed different
      tendencies. Albumin significantly decreased the cytotoxicity of ochratoxins. 2'R
      OTA, even at sub-toxic concentrations, increased the toxic action of OTA.

PMID- 30200463
TI  - Antioxidant Potential of Grass Pea Seeds from European Countries.
AB  - Phenolic compounds were extracted from seeds of 30 varieties of grass pea
      (Lathyrus sativus) into 80% (v/v) methanol. The total phenolics compounds content
      of the extracts and their antioxidant activity were determined using Folin
      Ciocalteu's phenol reagent and 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic
      acid) (ABTS) and ferric-reducing antioxidant power (FRAP) methods, respectively.
      Total phenolic contents ranged from 1.88 to 7.12 mg/g extract and 20.3 to 70.3
      mg/100 g seeds. The extracts and seeds were characterized using Trolox equivalent
      antioxidant capacity values of 0.015-0.037 mmol Trolox/g extract and 0.158-0.372
      mmol Trolox/100 g seeds, and FRAP values of 0.045-0.120 mmol Fe2+/g extract and
      0.487-1.189 Fe2+/100 g seeds. The total phenolics content of grass pea extract
      was correlated with the results of the ABTS (r = 0.881) and FRAP (r = 0.781)
      assays. The same correlation was observed between the results of both assays (r =
      0.842). Two derivatives of p-coumaric acid were the dominant phenolic compounds
      of the Derek cultivar of grass pea.

PMID- 30200464
TI  - Microbial Growth on Dust-Loaded Filtering Materials Used for the Protection of
      Respiratory Tract as a Factor Affecting Filtration Efficiency.
AB  - This work aims at understanding the effects of various dust-loading conditions
      and the type of nonwovens used in the construction of FFRs on the safe use of
      those protective devices in situations of exposure to biological agents. The
      survival of microorganisms (Escherichia coli, Candida albicans, and Aspergillus
      niger) in dust-loaded polypropylene nonwovens (melt-blown, spun-bonded, and
      needle-punched) was experimentally determined using microbiological quantitative
      method (AATCC TM 100-2004). Scanning electron microscope was used to assess
      biofilm formation on dust-loaded filtering nonwovens. The impact of the growth of
      microorganisms on filtration efficiency of nonwovens was analysed based on the
      measurements of penetration of sodium chloride particles (size range 7-270 nm).
      Results showed that tested microorganisms were able to survive on dust-loaded
      polypropylene filtering nonwovens. The survival rate of microorganisms and
      penetration of nanoparticles and submicron particles depended on the type of
      microorganism, as well as the type and the amount of dust, which indicates that
      both of those factors should be considered for FFR use recommendations.

PMID- 30200465
TI  - Glucose and Fat Tolerance Tests Induce Differential Responses in Plasma Choline
      Metabolites in Healthy Subjects.
AB  - Plasma choline shows associations with plasma glucose and lipids. We studied
      changes of choline metabolites after oral glucose tolerance test (OGTT) and fat
      tolerance test (OFTT). Eighteen healthy subjects (mean age 54.3 years; BMI 26.8
      kg/m2) underwent 2 tests. First, OFTT (80 g fat) was applied and blood was
      collected at baseline and 4 h after OFTT. Seven days later, 75 g glucose was
      applied and blood was collected at baseline and 2 h after OGTT. Plasma
      concentrations of choline, betaine, trimethylamine N-oxide (TMAO),
      dimethylglycine, S-adenosylmethionine (SAM), lipids and glucose were measured.
      After OFTT, plasma choline declined (10.6 to 9.2 umol/L; p = 0.004), betaine
      declined (33.4 to 31.7 umol/L; p = 0.003), TMAO slightly increased (4.1 to 5.6
      umol/L; p = 0.105), glucose declined (5.39 to 4.98 mmol/L; p < 0.001), and
      triglycerides increased (1.27 to 2.53 mmol/L; p < 0.001). After OGTT, plasma
      choline increased (10.1 to 11.1 umol/L; p < 0.001), TMAO declined (4.0 to 3.5
      umol/L; p = 0.029), dimethylglycine declined (2.0 to 1.7 umol/L; p = 0.005), SAM
      declined (103 to 96 nmol/L; p = 0.041), but betaine, glucose, and SAM were
      unchanged. In conclusion, OFTT lowered plasma betaine and choline and caused
      heterogeneous changes in plasma TMAO. OGTT reduced the flow of methyl groups and
      plasma TMAO.

PMID- 30200466
TI  - Analysis of the Spatial Variability of Soil Texture in a Tropical Highland: The
      Case of the Jema Watershed, Northwestern Highlands of Ethiopia.
AB  - This study sought to analyze the degree of spatial association of soil texture
      with agro-climatic zones and slope classes on the farmlands of the Jema
      watershed, in the Northwestern Highlands of Ethiopia. The agro-climatic zones
      (elevation zones) determine the micro-climate and biota of the study area. Thirty
      six soil composite samples for texture (the proportion of clay, silt and sand)
      analysis from four agro-climatic (elevation) zones and seven slope classes were
      collected. One-Way-ANOVA was employed to compute the mean variability of texture
      among the identified terrain classes, and linear regression was used to analyze
      the degree of association between texture and the terrain attributes. The
      measured values of sand, silt and clay in the watershed ranged from 11.4 to 43.4,
      6.0 to 34.8, and 21.8 to 77.8, respectively. The One-Way-ANOVA indicated a
      significant (p < 0.05) soil texture variation in both slope and agro-climatic
      zone classes. Heavy clay, clay and clay loam were identified as the major texture
      classes in the lower, middle and upper parts of the watershed, respectively. The
      regression analysis showed that texture was more influenced by the difference in
      the elevation values than in slope values in the watershed. The standardized beta
      coefficients of slope and elevation for clay particles were 0.499 and 0.767,
      respectively. For sand, the regression coefficients for slope and agro-climatic
      zone were 0.485 and 0.812, respectively. This implies that an interactive effect
      of micro-climate and biota governed by elevation influenced the spatial
      distribution of soil texture more than slope.

PMID- 30200467
TI  - Targeted UPLC-MS Metabolic Analysis of Human Faeces Reveals Novel Low-Invasive
      Candidate Markers for Colorectal Cancer.
AB  - Low invasive tests with high sensitivity for colorectal cancer and advanced
      precancerous lesions will increase adherence rates, and improve clinical
      outcomes. We have performed an ultra-performance liquid chromatography/time-of
      flight mass spectrometry (UPLC-(TOF) MS)-based metabolomics study to identify
      faecal biomarkers for the detection of patients with advanced neoplasia. A cohort
      of 80 patients with advanced neoplasia (40 advanced adenomas and 40 colorectal
      cancers) and 49 healthy subjects were analysed in the study. We evaluated the
      faecal levels of 105 metabolites including glycerolipids, glycerophospholipids,
      sterol lipids and sphingolipids. We found 18 metabolites that were significantly
      altered in patients with advanced neoplasia compared to controls. The
      combinations of seven metabolites including ChoE(18:1), ChoE(18:2), ChoE(20:4),
      PE(16:0/18:1), SM(d18:1/23:0), SM(42:3) and TG(54:1), discriminated advanced
      neoplasia patients from healthy controls. These seven metabolites were employed
      to construct a predictive model that provides an area under the curve (AUC)
      median value of 0.821. The inclusion of faecal haemoglobin concentration in the
      metabolomics signature improved the predictive model to an AUC of 0.885. In
      silico gene expression analysis of tumour tissue supports our results and puts
      the differentially expressed metabolites into biological context, showing that
      glycerolipids and sphingolipids metabolism and GPI-anchor biosynthesis pathways
      may play a role in tumour progression.

PMID- 30200469
TI  - Evaluation of Active Brown Adipose Tissue by the Use of Hyperpolarized [1
      13C]Pyruvate MRI in Mice.
AB  - The capacity to increase energy expenditure makes brown adipose tissue (BAT) a
      putative target for treatment of metabolic diseases such as obesity. Presently,
      investigation of BAT in vivo is mainly performed by fluoro-d-glucose positron
      emission tomography (FDG PET)/CT. However, non-radioactive methods that add
      information on, for example, substrate metabolism are warranted. Thus, the aim of
      this study was to evaluate the potential of hyperpolarized [1-13C]pyruvate
      Magnetic Resonance Imaging (HP-MRI) to determine BAT activity in mice following
      chronic cold exposure. Cold (6  degrees C) and thermo-neutral (30  degrees C)
      acclimated mice were scanned with HP-MRI for assessment of the interscapular BAT
      (iBAT) activity. Comparable mice were scanned with the conventional method FDG
      PET/MRI. Finally, iBAT was evaluated for gene expression and protein levels of
      the specific thermogenic marker, uncoupling protein 1 (UCP1). Cold exposure
      increased the thermogenic capacity 3-4 fold (p < 0.05) as measured by UCP1 gene
      and protein analysis. Furthermore, cold exposure as compared with thermo
      neutrality increased iBAT pyruvate metabolism by 5.5-fold determined by HP-MRI
      which is in good agreement with the 5-fold increment in FDG uptake (p < 0.05)
      measured by FDG PET/MRI. iBAT activity is detectable in mice using HP-MRI in
      which potential changes in intracellular metabolism may add useful information to
      the conventional FDG PET studies. HP-MRI may also be a promising radiation-free
      tool for repetitive BAT studies in humans.

PMID- 30200468
TI  - The Hydrophobin HYTLO1 Secreted by the Biocontrol Fungus Trichoderma
      longibrachiatum Triggers a NAADP-Mediated Calcium Signalling Pathway in Lotus
      japonicus.
AB  - Trichoderma filamentous fungi are increasingly used as biocontrol agents and
      plant biostimulants. Growing evidence indicates that part of the beneficial
      effects is mediated by the activity of fungal metabolites on the plant host. We
      have investigated the mechanism of plant perception of HYTLO1, a hydrophobin
      abundantly secreted by Trichoderma longibrachiatum, which may play an important
      role in the early stages of the plant-fungus interaction. Aequorin-expressing
      Lotus japonicus suspension cell cultures responded to HYTLO1 with a rapid
      cytosolic Ca2+ increase that dissipated within 30 min, followed by the activation
      of the defence-related genes MPK3, WRK33, and CP450. The Ca2+-dependence of these
      gene expression was demonstrated by using the extracellular Ca2+ chelator EGTA
      and Ned-19, a potent inhibitor of the nicotinic acid adenine dinucleotide
      phosphate (NAADP) receptor in animal cells, which effectively blocked the HYTLO1
      induced Ca2+ elevation. Immunocytochemical analyses showed the localization of
      the fungal hydrophobin at the plant cell surface, where it forms a protein film
      covering the plant cell wall. Our data demonstrate the Ca2+-mediated perception
      by plant cells of a key metabolite secreted by a biocontrol fungus, and provide
      the first evidence of the involvement of NAADP-gated Ca2+ release in a signalling
      pathway triggered by a biotic stimulus.

PMID- 30200470
TI  - Impact of Antidepressant Use on Healthcare Utilization among Individuals with
      Type 2 Diabetes and Depression Symptoms in the United States: Sociodemographic,
      Clinical, and Behavioral Factors Matter.
AB  - Individuals with diabetes are twice as likely to struggle from depressive
      symptoms than individuals without diabetes. However, this joint condition is
      undertreated in nearly two-thirds of patients. Failure to monitor the comorbidity
      may lead to suboptimal therapy. This study evaluated the association of
      antidepressant use with healthcare utilization in a national sample of patients
      with type 2 diabetes and depression symptoms in the United States. It further
      assessed the differences in sociodemographic, clinical, and behavioral factors
      between those who use antidepressants and those who do not. This study was a
      secondary data analysis using the National Health and Nutrition Examination
      Survey (NHANES) for the period 2005-2014. To assess if there were significant
      differences in sociodemographic, clinical, and behavioral factors between those
      who were taking antidepressants or not, Chi Square and independent t-tests were
      used. To assess if there was a significant association between antidepressant use
      and healthcare utilization, univariate and multivariate regression analyses were
      conducted. Of the 955 participants, only 33% were on antidepressants. There were
      significant differences in sociodemographic, clinical, and behavioral factors
      among those who used antidepressants and those who did not. Regardless of
      antidepressant use, the study population had access to health care. Those on
      antidepressants had fewer diabetes specialists' visits and more mental health
      care. There might be underlying health care disparities related to the use of,
      and access to, antidepressants. Further studies are needed to comprehensively
      explore the management of these comorbidities.

PMID- 30200471
TI  - Modulation of Iron Metabolism in Response to Infection: Twists for All Tastes.
AB  - Iron is an essential nutrient for almost all living organisms, but is not easily
      made available. Hosts and pathogens engage in a fight for the metal during an
      infection, leading to major alterations in the host's iron metabolism. Important
      pathological consequences can emerge from the mentioned interaction, including
      anemia. Several recent reports have highlighted the alterations in iron
      metabolism caused by different types of infection, and several possible
      therapeutic strategies emerge, based on the targeting of the host's iron
      metabolism. Here, we review the most recent literature on iron metabolism
      alterations that are induced by infection, the consequent development of anemia,
      and the potential therapeutic approaches to modulate iron metabolism in order to
      correct iron-related pathologies and control the ongoing infection.

PMID- 30200475
TI  - Kinematic Calibration of a Cable-Driven Parallel Robot for 3D Printing.
AB  - Three-dimensional (3D) printing technology has been greatly developed in the last
      decade and gradually applied in the construction, medical, and manufacturing
      industries. However, limited workspace and accuracy restrict the development of
      3D printing technology. Due to the extension range and flexibility of cables,
      cable-driven parallel robots can be applied in challenging tasks that require
      motion with large reachable workspace and better flexibility. In this paper, a
      cable-driven parallel robot for 3D Printing is developed to obtain larger
      workspace rather than traditional 3D printing devices. A kinematic calibration
      method is proposed based on cable length residuals. On the basis of the kinematic
      model of the cable-driven parallel robot for 3D Printing, the mapping model is
      established among geometric structure errors, zero errors of the cable length,
      and end-effector position errors. In order to improve the efficiency of
      calibration measurement, an optimal scheme for measurement positions is proposed.
      The accuracy and efficiency of the kinematics calibration method are verified
      through numerical simulation. The calibration experiment based on the motion
      capture system indicates that the position error of end-effector is decreased to
      0.6157 mm after calibration. In addition, the proposed calibration method is
      effective and verified for measurement positions outside optimal positions set
      through experiments.

PMID- 30200473
TI  - Chitosan Inhibits the Rehabilitation of Damaged Microbes Induced by Photodynamic
      Inactivation.
AB  - Previously, we showed that chitosan could augment the biocidal efficacy mediated
      by photodynamic treatment against Staphylococcus aureus, Pseudomonas aeruginosa,
      and Candida albicans. In this study, we showed that the antimicrobial action of
      chitosan in augmenting photodynamic inactivation (PDI) is related to the increase
      in cell surface destruction. The microbial cell surfaces exhibit severe irregular
      shapes after PDI in the presence of chitosan as demonstrated by transmitted
      electron microscopy. Furthermore, increases in the concentration or incubation
      time of chitosan significantly reduced the amounts of photosensitizer toluidine
      blue O required, indicating that chitosan could be an augmenting agent used in
      conjunction with PDI against S. aureus, P. aeruginosa, and C. albicans. A
      prolonged lag phase was found in microbial cells that survived to PDI, in which
      chitosan acted to completely eradicate the cells. Once the exponential log stage
      and cell rebuild began, their cellular functions from PDI-induced damage returned
      and the increased cytotoxic effect of chitosan disappeared. Together, our results
      suggest that chitosan can prevent the rehabilitation of PDI-surviving microbial
      cells, leading to increased biocidal efficacy.

PMID- 30200474
TI  - Excited State Structural Evolution of a GFP Single-Site Mutant Tracked by Tunable
      Femtosecond-Stimulated Raman Spectroscopy.
AB  - Tracking vibrational motions during a photochemical or photophysical process has
      gained momentum, due to its sensitivity to the progression of reaction and change
      of environment. In this work, we implemented an advanced ultrafast vibrational
      technique, femtosecond-stimulated Raman spectroscopy (FSRS), to monitor the
      excited state structural evolution of an engineered green fluorescent protein
      (GFP) single-site mutant S205V. This mutation alters the original excited state
      proton transfer (ESPT) chain. By strategically tuning the Raman pump to different
      wavelengths (i.e., 801, 539, and 504 nm) to achieve pre-resonance with transient
      excited state electronic bands, the characteristic Raman modes of the excited
      protonated (A*) chromophore species and intermediate deprotonated (I*) species
      can be selectively monitored. The inhomogeneous distribution/population of A*
      species go through ESPT with a similar ~300 ps time constant, confirming that
      bridging a water molecule to protein residue T203 in the ESPT chain is the rate
      limiting step. Some A* species undergo vibrational cooling through high-frequency
      motions on the ~190 ps time scale. At early times, a portion of the largely
      protonated A* species could also undergo vibrational cooling or return to the
      ground state with a ~80 ps time constant. On the photoproduct side, a ~1330 cm-1
      delocalized motion is observed, with dispersive line shapes in both the Stokes
      and anti-Stokes FSRS with a pre-resonance Raman pump, which indicates strong
      vibronic coupling, as the mode could facilitate the I* species to reach a
      relatively stable state (e.g., the main fluorescent state) after conversion from
      A*. Our findings disentangle the contributions of various vibrational motions
      active during the ESPT reaction, and offer new structural dynamics insights into
      the fluorescence mechanisms of engineered GFPs and other analogous
      autofluorescent proteins.

PMID- 30200472
TI  - HIV-1 Envelope Protein gp120 Promotes Proliferation and the Activation of
      Glycolysis in Glioma Cell.
AB  - Patients infected with human immunodeficiency virus (HIV) are more prone to
      developing cancers, including glioblastomas (GBMs). The median survival for HIV
      positive GBM patients is significantly shorter than for those who are uninfected,
      despite the fact that they receive the same treatments. The nature of the GBM-HIV
      association remains poorly understood. In this study, we analyzed the effect of
      the HIV envelope glycoprotein gp120 on GBM cell proliferation. Specifically, we
      performed cell cycle, western blot, protein synthesis and metabolomics analysis
      as well as ATP production and oxygen consumption assays to evaluate proliferation
      and metabolic pathways in primary human glioma cell line, U87, A172 cells and in
      the HIVgp120tg/GL261 mouse model. Glioma cells treated with gp120 (100 ng/mL for
      7-10 days) showed higher proliferation rates and upregulation in the expression
      of enolase 2, hexokinase and glyceraldehyde-3-phosphate dehydrogenase when
      compared to untreated cells. Furthermore, we detected an increase in the activity
      of pyruvate kinase and a higher glycolytic index in gp120 treated cells. Gp120
      treated GBM cells also showed heightened lipid and protein synthesis. Overall, we
      demonstrate that in glioma cells, the HIV envelope glycoprotein promotes
      proliferation and activation of glycolysis resulting in increased protein and
      lipid synthesis.

PMID- 30200476
TI  - Heck Transformations of Biological Compounds Catalyzed by Phosphine-Free
      Palladium.
AB  - The development and optimization of synthetic methods leading to functionalized
      biologically active compounds is described. Two alternative pathways based on
      Heck-type reactions, employing iodobenzene or phenylboronic acid, were elaborated
      for the arylation of eugenol and estragole. Cinnamyl alcohol was efficiently
      transformed to saturated arylated aldehydes in reaction with iodobenzene using
      the tandem arylation/isomerization sequential process. The arylation of cinnamyl
      alcohol with phenylboronic acid mainly gave unsaturated alcohol, while the yield
      of saturated aldehyde was much lower. Catalytic reactions were carried out using
      simple, phosphine-free palladium precursors and water as a cosolvent, following
      green chemistry rules as much as possible.

PMID- 30200477
TI  - A Fluorescent Cy7-Mercaptopyridine for the Selective Detection of Glutathione
      over Homocysteine and Cysteine.
AB  - We describe a near-infrared (NIR) fluorescent probe 1 for the selective detection
      of GSH over Hcy and Cys under physiological conditions. Probe 1 was composed of
      Cy7 as a NIR dye and 2-mercaptopyridine as a GSH-reactive site and fluorescence
      quencher. In the presence of GSH, the 2-mercaptopyridine functionality of probe 1
      was replaced by the thiolate group of GSH through a nucleophilic substitution
      reaction with a fluorescence increase at 818 nm. The probe was found to be highly
      selective for GSH over Hcy, Cys, and other tested potential interferants,
      including ROS and metal ions. In addition, probe 1 successfully displayed
      fluorescence changes in response to changing the GSH concentrations in MDA-MB-231
      cells in the presence of external agents i.e., N-acetyl-l-cysteine (NAC; as GSH
      inducer) or buthionine sulfoximine (BSO; as GSH inhibitor). We envision that
      probe 1 will serve as a promising sensing tool for monitoring the changes of the
      GSH level and the understanding of the roles of GSH under physiological and
      pathological conditions.

PMID- 30200479
TI  - Early Influence of Musical Abilities and Working Memory on Speech Imitation
      Abilities: Study with Pre-School Children.
AB  - Musical aptitude and language talent are highly intertwined when it comes to
      phonetic language ability. Research on pre-school children's musical abilities
      and foreign language abilities are rare but give further insights into the
      relationship between language and musical aptitude. We tested pre-school
      children's abilities to imitate unknown languages, to remember strings of digits,
      to sing, to discriminate musical statements and their intrinsic (spontaneous)
      singing behavior ("singing-lovers versus singing nerds"). The findings revealed
      that having an ear for music is linked to phonetic language abilities. The
      results of this investigation show that a working memory capacity and phonetic
      aptitude are linked to high musical perception and production ability already at
      around the age of 5. This suggests that music and (foreign) language learning
      capacity may be linked from childhood on. Furthermore, the findings put emphasis
      on the possibility that early developed abilities may be responsible for
      individual differences in both linguistic and musical performances.

PMID- 30200480
TI  - Detection of Functional Overreaching in Endurance Athletes Using Proteomics.
AB  - No reliable biomarkers exist to identify athletes in various training states
      including functional overreaching (FOR), non-functional overreaching (NFOR), and
      overtraining syndrome (OTS). Participants (N = 10, age 38.3 +/- 3.4 years) served
      as their own controls and in random, counterbalanced order either ran/cycled 2.5
      h (70.0 +/- 3.7% VO2max) three days in a row (FOR) or sat in the lab (rest)
      (separated by three weeks; 7:00-9:30 am, overnight fasted state). Participants
      provided fingerprick samples for dried blood spot samples (DBS) pre- and post
      exercise/rest, and then during two recovery days. DBS proteins were measured with
      nanoLC-MS in data-independent acquisition (DIA) mode, and 593 proteins were
      identified and quantified. Proteins were considered for the FOR cluster if they
      were elevated during one of the two recovery days but not more than one of the
      exercise days (compared to rest). The generalized estimating equation (GEE) was
      used to identify proteins linked to FOR. A total of 13 proteins was linked to FOR
      and most were associated with the acute phase response and innate immune system
      activation. This study used a system-wide proteomics approach to define a
      targeted panel of blood proteins related to FOR that could form the basis of
      future NFOR- and OTS-based studies.

PMID- 30200478
TI  - Regulation of Ovarian Cancer Prognosis by Immune Cells in the Tumor
      Microenvironment.
AB  - It is estimated that in the United States in 2018 there will be 22,240 new cases
      of ovarian cancer and 14,070 deaths due to this malignancy. The most common
      subgroup of this disease is high-grade serous ovarian cancer (HGSOC), which is
      known for its aggressiveness, high recurrence rate, metastasis to other sites,
      and the development of resistance to conventional therapy. It is important to
      understand the ovarian cancer tumor microenvironment (TME) from the viewpoint of
      the function of pre-existing immune cells, as immunocompetent cells are crucial
      to mounting robust antitumor responses to prevent visible tumor lesions, disease
      progression, or recurrence. Networks consisting of innate and adaptive immune
      cells, metabolic pathways, intracellular signaling molecules, and a vast array of
      soluble factors, shape the pathogenic nature of the TME and are useful prognostic
      indicators of responses to conventional therapy and immunotherapy, and subsequent
      survival rates. This review highlights key immune cells and soluble molecules in
      the TME of ovarian cancer, which are important in the development of effective
      antitumor immunity, as well as those that impair effector T cell activity. A more
      insightful knowledge of the HGSOC TME will reveal potential immune biomarkers to
      aid in the early detection of this disease, as well as biomarkers that may be
      targeted to advance the design of novel therapies that induce potent antitumor
      immunity and survival benefit.

PMID- 30200481
TI  - The Effect of Permethrin Resistance on Aedes aegypti Transcriptome Following
      Ingestion of Zika Virus Infected Blood.
AB  - Aedes aegypti (L.) is the primary vector of many emerging arboviruses.
      Insecticide resistance among mosquito populations is a consequence of the
      application of insecticides for mosquito control. We used RNA-sequencing to
      compare transcriptomes between permethrin resistant and susceptible strains of
      Florida Ae. aegypti in response to Zika virus infection. A total of 2459
      transcripts were expressed at significantly different levels between resistant
      and susceptible Ae. aegypti. Gene ontology analysis placed these genes into seven
      categories of biological processes. The 863 transcripts were expressed at
      significantly different levels between the two mosquito strains (up/down
      regulated) more than 2-fold. Quantitative real-time PCR analysis was used to
      validate the Zika-infection response. Our results suggested a highly
      overexpressed P450, with AAEL014617 and AAEL006798 as potential candidates for
      the molecular mechanism of permethrin resistance in Ae. aegypti. Our findings
      indicated that most detoxification enzymes and immune system enzymes altered
      their gene expression between the two strains of Ae. aegypti in response to Zika
      virus infection. Understanding the interactions of arboviruses with resistant
      mosquito vectors at the molecular level allows for the possible development of
      new approaches in mitigating arbovirus transmission. This information sheds light
      on Zika-induced changes in insecticide resistant Ae. aegypti with implications
      for mosquito control strategies.

PMID- 30200482
TI  - Untargeted Metabolomics Analysis of Eggplant (Solanum melongena L.) Fruit and Its
      Correlation to Fruit Morphologies.
AB  - Eggplant is one of the most widely cultivated vegetables in the world and has
      high biodiversity in terms of fruit shape, size, and color. Therefore, fruit
      morphology and nutrient content become important considerations for both
      consumers and breeders who develop new eggplant-based products. To gain insight
      on the diversity of eggplant metabolites, twenty-one eggplant accessions were
      analyzed by untargeted metabolomics using GC-MS and LC-MS. The dataset of
      eggplant fruit morphologies, and metabolites specific to different eggplant fruit
      accessions were used for correlation analysis. Untargeted metabolomics analysis
      using LC-MS and GC-MS was able to detect 136 and 207 peaks, respectively. Fifty
      one (51) metabolites from the LC-MS analysis and 207 metabolites from the GC-MS
      analysis were putatively identified, which included alkaloids, terpenes,
      terpenoids, fatty acids, and flavonoids. Spearman correlation analysis revealed
      that 14 fruit morphologies were correlated with several metabolites. This
      information will be very useful for the development of strategies for eggplant
      breeding.

PMID- 30200483
TI  - Oxidative Asymmetric Formal Aza-Diels-Alder Reactions of Tetrahydro-beta
      carboline with Enones in the Synthesis of Indoloquinolizidine-2-ones.
AB  - Ru-catalyzed tandem amine oxidative dehydrogenation/formal aza-Diels-Alder
      reaction for enantio- and diastereoselective synthesis of indoloquinolizidine-2
      ones from tetrahydro-beta-carbolines and alpha,beta-unsaturated ketones is
      described. The reaction proceeds via tandem ruthenium-catalyzed amine
      dehydrogenation using tert-butyl hydroperoxide (TBHP) as the oxidant and a chiral
      thiourea-catalyzed formal aza-[4 + 2] cycloaddition, providing a step-economical
      strategy for the synthesis of these valuable heterocyclic products.

PMID- 30200484
TI  - A Clustering WSN Routing Protocol Based on k-d Tree Algorithm.
AB  - Clustering in wireless sensor networks has been widely discussed in the
      literature as a strategy to reduce power consumption. However, aspects such as
      cluster formation and cluster head (CH) node assignment strategies have a
      significant impact on quality of service, as energy savings imply restrictions in
      application usage and data traffic within the network. Regarding the first
      aspect, this article proposes a hierarchical routing protocol based on the k-d
      tree algorithm, taking a partition data structure of the space to organize nodes
      into clusters. For the second aspect, we propose a reactive mechanism for the
      formation of CH nodes, with the purpose of improving delay, jitter, and
      throughput, in contrast with the low-energy adaptive clustering
      hierarchy/hierarchy-centralized protocol and validating the results through
      simulation.

PMID- 30200485
TI  - Potentiality of Using Luojia 1-01 Nighttime Light Imagery to Investigate
      Artificial Light Pollution.
AB  - The successful launch of Luojia 1-01 complements the existing nighttime light
      data with a high spatial resolution of 130 m. This paper is the first study to
      assess the potential of using Luojia 1-01 nighttime light imagery for
      investigating artificial light pollution. Eight Luojia 1-01 images were selected
      to conduct geometric correction. Then, the ability of Luojia 1-01 to detect
      artificial light pollution was assessed from three aspects, including the
      comparison between Luojia 1-01 and the Suomi National Polar-Orbiting Partnership
      Visible Infrared Imaging Radiometer Suite (NPP-VIIRS), the source of artificial
      light pollution and the patterns of urban light pollution. Moreover, the
      advantages and limitations of Luojia 1-01 were discussed. The results showed the
      following: (1) Luojia 1-01 can detect a higher dynamic range and capture the
      finer spatial details of artificial nighttime light. (2) The averages of the
      artificial light brightness were different between various land use types. The
      brightness of the artificial light pollution of airports, streets, and commercial
      services is high, while dark areas include farmland and rivers. (3) The light
      pollution patterns of four cities decreased away from the urban core and the
      total light pollution is highly related to the economic development. Our findings
      confirm that Luojia 1-01 can be effectively used to investigate artificial light
      pollution. Some limitations of Luojia 1-01, including its spectral range,
      radiometric calibration and the effects of clouds and moonlight, should be
      researched in future studies.

PMID- 30200486
TI  - Effects of Sunitinib and Other Kinase Inhibitors on Cells Harboring a PDGFRB
      Mutation Associated with Infantile Myofibromatosis.
AB  - Infantile myofibromatosis represents one of the most common proliferative fibrous
      tumors of infancy and childhood. More effective treatment is needed for drug
      resistant patients, and targeted therapy using specific protein kinase inhibitors
      could be a promising strategy. To date, several studies have confirmed a
      connection between the p.R561C mutation in gene encoding platelet-derived growth
      factor receptor beta (PDGFR-beta) and the development of infantile
      myofibromatosis. This study aimed to analyze the phosphorylation of important
      kinases in the NSTS-47 cell line derived from a tumor of a boy with infantile
      myofibromatosis who harbored the p.R561C mutation in PDGFR-beta. The second aim
      of this study was to investigate the effects of selected protein kinase
      inhibitors on cell signaling and the proliferative activity of NSTS-47 cells. We
      confirmed that this tumor cell line showed very high phosphorylation levels of
      PDGFR-beta, extracellular signal-regulated kinases (ERK) 1/2 and several other
      protein kinases. We also observed that PDGFR-beta phosphorylation in tumor cells
      is reduced by the receptor tyrosine kinase inhibitor sunitinib. In contrast,
      MAPK/ERK kinases (MEK) 1/2 and ERK1/2 kinases remained constitutively
      phosphorylated after treatment with sunitinib and other relevant protein kinase
      inhibitors. Our study showed that sunitinib is a very promising agent that
      affects the proliferation of tumor cells with a p.R561C mutation in PDGFR-beta.

PMID- 30200487
TI  - Seroprevalence of Markers of Hepatitis B Virus Infection, Associated Factors, and
      Vaccination Status in Young Adults in Arkhangelsk, Northwest Russia: A Population
      Based Cross-Sectional Study.
AB  - Russia had a high incidence of hepatitis B virus (HBV) infection before the
      vaccination campaigns of 1997, 2001, 2007, which targeted newborns, adolescents,
      and adults, respectively. The aim of our study was to assess the prevalence of
      serological markers of HBV infection, associated factors, and vaccination status
      among young adults in Arkhangelsk, Northwest Russia. In this cross-sectional,
      population-based study, we used a quota sampling method to recruit 1243 adults
      aged 18-39 years. Participants completed a self-administrated questionnaire and
      were tested for hepatitis B markers. Associations between positivity for markers
      and selected sociodemographic and behavioral factors were studied by logistic
      regression. 10.9% of our participants were positive for at least one marker of
      hepatitis B, 1.2% were positive for HBsAg, and 42.1% were negative for all
      markers. In multivariable logistic regression analyses, age 30-34 years; lack of
      self-reported vaccination; and having >=2 sexual partners in the last 6 months
      were associated with positivity for markers of hepatitis B. Hepatitis B
      vaccination was confirmed in 46.9% of participants. Although half of our study
      sample was vaccinated, four in 10 were still susceptible to infection and more
      than one participant in 100 showed evidence of an active infection.

PMID- 30200488
TI  - Fluorescent Thienothiophene-Containing Squaraine Dyes and Threaded Supramolecular
      Complexes with Tunable Wavelengths between 600-800 nm.
AB  - A new family of fluorescent thiophene and thienothiophene-containing squaraine
      dyes is described with tunable wavelengths that cover the absorption/emission
      range of 600-800 nm. The deep-red and near-infrared fluorescent compounds were
      easily prepared by simple synthesis and purification methods. Spectral studies
      showed that each squaraine was rapidly encapsulated by a tetralactam macrocycle,
      with nanomolar affinity in water, to produce a threaded supramolecular complex
      with high chemical stability, increased fluorescence quantum yield, and decreased
      fluorescence quenching upon dye self-aggregation. Energy transfer within the
      supramolecular complex permitted multiplex emission. That is, two separate dyes
      with fluorescence emission bands that match the popular Cy5 and Cy7 channels,
      could be simultaneously excited with a beam of 375 nm light. A broad range of
      practical applications is envisioned in healthcare diagnostics, microscopy,
      molecular imaging, and fluorescence-guided surgery.

PMID- 30200489
TI  - Ruthenium Oxide Nanorods as Potentiometric pH Sensor for Organs-On-Chip Purposes.
AB  - A ruthenium oxide (RuOx) sensor for potentiometric pH sensing is currently being
      developed for organs-on-chip purposes. The sensor was fabricated from a Ru(OH)3
      precursor, resulting in RuOx nanorods after heating. An open-circuit potential of
      the RuOx electrode showed a near-Nernstian response of -58.05 mV/pH, with good
      selectivity against potentially interfering ions (lithium, sulfate, chloride, and
      calcium ions). The preconditioned electrode (stored in liquid) had a long-term
      drift of -0.8 mV/h, and its response rate was less than 2 s. Sensitivity to
      oxygen was observed at an order of magnitude lower than other reported metal
      oxide pH sensors. Together with miniaturizability, the RuOx pH sensor proves to
      be a suitable pH sensor for organs-on-chip studies.

PMID- 30200490
TI  - Skin Penetration and Stability Enhancement of Celastrus paniculatus Seed Oil by 2
      Hydroxypropyl-beta-Cyclodextrin Inclusion Complex for Cosmeceutical Applications.
AB  - This study aimed to encapsulate Celastrus paniculatus seed oil (CPSO) in 2
      hydroxypropyl-beta-cyclodextrin (HPbetaCD) cavities and investigate their
      biological activity, physicochemical stability, and skin penetration by vertical
      Franz diffusion cells of the CPSO-HPbetaCD inclusion complex formulations. For
      biological activity studies-including 2,2-diphenyl-1-picryhydrazyl radical (DPPH)
      scavenging, metal ion chelating, and inhibition of lipid and tyrosinase
      inhibition activities-the CPSO-HPbetaCD inclusion complex exhibited lower
      inhibition activity than free CPSO. CPSO-HPbetaCD dispersion, serum, and gel
      formulations were prepared. All formulations containing the CPSO-HPbetaCD
      inclusion complex showed no significant changes in physical characteristics after
      three months' storage. The percentages of oleic acid remaining in all
      formulations were over 80% of the initial amount during a three-month stability
      study. For the skin-penetration study, compared to other formulations, the CPSO
      HPbetaCD serum formulation exhibited the highest cumulative amount of oleic acid
      in the whole skin and flux through receptor fluid, after six hours, of 32.75 +/-
      1.25 ug/cm2 and 1.02 +/- 0.15 ug/cm2/h, respectively. The CPSO-HPbetaCD serum
      formulation also showed the proper viscosity. Hence, the CPSO-HPbetaCD inclusion
      complex will be beneficial for the further development of cosmeceutical products.

PMID- 30200491
TI  - Cerium Oxide Nanoparticles Sensitize Pancreatic Cancer to Radiation Therapy
      through Oxidative Activation of the JNK Apoptotic Pathway.
AB  - Side effects of radiation therapy (RT) remain the most challenging issue for
      pancreatic cancer treatment. Cerium oxide nanoparticles (CONPs) are currently
      being tested in pre-clinical trials as an adjuvant to sensitize pancreatic cancer
      cells to RT and protect normal tissues from the harmful side effects. CONPs were
      not able to significantly affect RT-induced DNA damage in cancer cells, thereby
      ruling out sensitization through increased mitotic catastrophe. However,
      activation of c-Jun terminal kinase (JNK), a key driver of RT-induced apoptosis,
      was significantly enhanced by co-treatment with CONPs and RT in pancreatic cancer
      cells in vitro and human pancreatic tumors in nude mice in vivo compared to CONPs
      or RT treatment alone. Further, CONP-driven increase in RT-induced JNK activity
      was associated with a marked increase in Caspase 3/7 activation, indicative of
      apoptosis. We have previously shown that CONPs increase reactive oxygen species
      (ROS) production in cancer cells. ROS has been shown to drive the oxidation of
      thioredoxin 1 (TRX1) which results in the activation of apoptosis signaling
      kinase 1 (ASK1). The increase in ASK1 activation following the co-treatment with
      CONPs followed by RT suggests that the increased JNK activation is the result of
      increased TRX1 oxidation. The ability of CONPs to sensitize pancreatic cancer
      cells to RT was mitigated when the TRX1 oxidation was prevented by mutagenesis of
      a cysteine residue or when the JNK activation was blocked by an inhibitor. Taken
      together, these data demonstrate an important mechanism for CONPs in specifically
      killing cancer cells and provide novel insights into the utilization of CONPs as
      a radiosensitizer and therapeutic agent for pancreatic cancer.

PMID- 30200493
TI  - Comparison and Feasibility of Various RFID Authentication Methods Using ECC.
AB  - Radio frequency identification (RFID) is a technology that has grown in
      popularity and in the applications of use. However, there are major issues
      regarding security and privacy with respect to RFID technology which have caught
      the interest of many researchers. There are significant challenges which must be
      overcome to resolve RFID security and privacy issues. One reason is the
      constraints attached to the provision of security and privacy in RFID systems.
      Along with meeting the security and privacy needs of RFID technology, solutions
      must be inexpensive, practical, reliable, scalable, flexible, inter
      organizational, and long-lasting. To make RFID identifiers effective and
      efficient they must identify the item(s) while resisting attacks aimed at
      obtaining the tag's information and compromising the system or making it possible
      to bypass the protection RFID tags are supposed to provide. Different
      authentication methods have been proposed, researched, and evaluated in the
      literature. In this work, we proposed our methodology in evaluating RFID
      authentication, and a few of the most promising authentication methods are
      reviewed, compared, and ranked in order to arrive at a possible best choice of
      protocol to use.

PMID- 30200494
TI  - Target Tracking While Jamming by Airborne Radar for Low Probability of Detection.
AB  - Although radiation power minimization is the most important method for an
      advanced stealth aircraft to achieve the low probability of detection (LPD)
      performance against the opposite passive detection system (PDS), it is not always
      effective when the performance of PDS is advanced. In a target tracking scenario,
      an interference tactic is proposed in this paper to keep the airborne radar in an
      LPD state. Firstly, this paper introduces the minimization radiation power design
      of airborne radar based on the distance between the radar and the target, and
      introduces the minimization radiation power design of the airborne jammer based
      on the predicted detection probability of the opposite PDS. Then, after
      consulting the most commonly used constant false alarm rate (CFAR) technologies
      in passive detection systems, including the cell average CFAR, the greatest of
      CFAR, the smallest of CFAR and the ordered statistic CFAR, this paper analyzes
      their relationships and points out the way of interference. Finally, based on the
      constraints, not only including the predicted detection probabilities of airborne
      radar and opposite PDS, respectively, but also including the time synchronization
      which is necessary to avoid the leaked interference power generated by airborne
      jammer jamming the airborne radar echoes from the target, this paper establishes
      a math model to minimize the total interference power of airborne jammer without
      interfering target tracking. Simulation results show that the proposed model is
      effective.

PMID- 30200492
TI  - Hidden Hunger: Solutions for America's Aging Populations.
AB  - The global population, including the United States, is experiencing a demographic
      shift with the proportion of older adults (aged >= 65 years) growing faster than
      any other age group. This demographic group is at higher risk for developing
      nutrition-related chronic conditions such as heart disease and diabetes as well
      as infections such as influenza and pneumonia. As a result, an emphasis on
      nutrition is instrumental for disease risk reduction. Unfortunately, inadequate
      nutrient status or deficiency, often termed hidden hunger, disproportionately
      affects older adults because of systematic healthcare, environmental, and
      biological challenges. This report summarizes the unique nutrition challenges
      facing the aging population and identifies strategies, interventions, and
      policies to address hidden hunger among the older adults, discussed at the
      scientific symposium "Hidden Hunger: Solutions for America's Aging Population",
      on March 23, 2018.

PMID- 30200495
TI  - Ginsenoside Rh2 Ameliorates Lipopolysaccharide-Induced Acute Lung Injury by
      Regulating the TLR4/PI3K/Akt/mTOR, Raf-1/MEK/ERK, and Keap1/Nrf2/HO-1 Signaling
      Pathways in Mice.
AB  - The anti-inflammatory effect of ginsenoside Rh2 (GRh2) has labeled it as one of
      the most important ginsenosides. The purpose of this study was to identify the
      anti-inflammatory and antioxidant effects of GRh2 using a lipopolysaccharide
      (LPS) challenge lung-injury animal model. GRh2 reduced LPS-induced
      proinflammatory mediator nitric oxide (NO), tumor necrosis factor-alpha,
      interleukin (IL)-1beta, and anti-inflammatory cytokines (IL-4, IL-6, and IL-10)
      production in lung tissues. GRh2 treatment decreased the histological alterations
      in the lung tissues and bronchoalveolar lavage fluid (BALF) protein content;
      total cell number also reduced in LPS-induced lung injury in mice. Moreover, GRh2
      blocked iNOS, COX-2, the phosphorylation of IkappaB-alpha, ERK, JNK, p38, Raf-1,
      and MEK protein expression, which corresponds with the growth of HO-1, Nrf-2,
      catalase, SOD, and GPx expression in LPS-induced lung injury. An in vivo
      experimental study suggested that GRh2 has anti-inflammatory effects, and has
      potential therapeutic efficacy in major anterior segment lung diseases.

PMID- 30200496
TI  - Energy-Effective Power Control Algorithm with Mobility Prediction for 5G
      Heterogeneous Cloud Radio Access Network.
AB  - In 5G networks, heterogeneous cloud radio access network (H-CRAN) is considered a
      promising future architecture to minimize energy consumption and efficiently
      allocate resources. However, with the increase in the number of users, studies
      are performed to overcome the energy consumption problems. In this study, we
      propose a power control algorithm with mobility prediction to provide a high
      energy efficiency for 5G H-CRAN. In particular, the proposed algorithm predicts
      UE mobility in vehicular mobility scenarios and performs remote radio head (RRH)
      switching operations based on % prediction results. We formulate an optimization
      problem to maximize the energy efficiency while satisfying the outage probability
      requirement. We then propose an RRH switching operation based on Markov mobility
      prediction and optimize the transmission power based on a gradient method.
      Simulation results demonstrate the improved energy efficiency compared with those
      of existing RRH switching-operation algorithms.

PMID- 30200498
TI  - Effect of Temperature and Hold Time of Induction Brazing on Microstructure and
      Shear Strength of Martensitic Stainless Steel Joints.
AB  - 1Cr12Mo martensitic stainless steel is widely used for intermediate and low
      pressure steam turbine blades in fossil-fuel power plants. A nickel-based filler
      metal (SFA-5.8 BNi-2) was used to braze 1Cr12Mo in an Ar atmosphere. The
      influence of brazing temperature and hold time on the joints was studied.
      Microstructure of the joints brazed, element distribution and shear stress were
      evaluated at different brazing temperatures, ranging from 1050  degrees C to 1120
      degrees C, with holding times of 10 s, 30 s, 50 s and 90 s. The results show
      that brazing joints mainly consist of the matrix of the braze alloy, the
      precipitation, and the diffusion affected zone. The filler metal elements
      diffusion is more active with increased brazing temperature and prolonged hold
      time. The shear strength of the brazed joints is greater than 250 MPa when the
      brazing temperature is 1080  degrees C and the hold time is 30 s.

PMID- 30200497
TI  - HDAC Inhibition Counteracts Metastatic Re-Activation of Prostate Cancer Cells
      Induced by Chronic mTOR Suppression.
AB  - This study was designed to investigate whether epigenetic modulation by histone
      deacetylase (HDAC) inhibition might circumvent resistance towards the mechanistic
      target of rapamycin (mTOR) inhibitor temsirolimus in a prostate cancer cell
      model. Parental (par) and temsirolimus-resistant (res) PC3 prostate cancer cells
      were exposed to the HDAC inhibitor valproic acid (VPA), and tumor cell adhesion,
      chemotaxis, migration, and invasion were evaluated. Temsirolimus resistance was
      characterized by reduced binding of PC3res cells to endothelium, immobilized
      collagen, and fibronectin, but increased adhesion to laminin, as compared to the
      parental cells. Chemotaxis, migration, and invasion of PC3res cells were enhanced
      following temsirolimus re-treatment. Integrin alpha and beta receptors were
      significantly altered in PC3res compared to PC3par cells. VPA significantly
      counteracted temsirolimus resistance by down-regulating tumor cell-matrix
      interaction, chemotaxis, and migration. Evaluation of integrin expression in the
      presence of VPA revealed a significant down-regulation of integrin alpha5 in
      PC3res cells. Blocking studies demonstrated a close association between alpha5
      expression on PC3res and chemotaxis. In this in vitro model, temsirolimus
      resistance drove prostate cancer cells to become highly motile, while HDAC
      inhibition reversed the metastatic activity. The VPA-induced inhibition of
      metastatic activity was accompanied by a lowered integrin alpha5 surface level on
      the tumor cells.

PMID- 30200499
TI  - Intelligent Land-Vehicle Model Transfer Trajectory Planning Method Based on Deep
      Reinforcement Learning.
AB  - To address the problem of model error and tracking dependence in the process of
      intelligent vehicle motion planning, an intelligent vehicle model transfer
      trajectory planning method based on deep reinforcement learning is proposed,
      which is able to obtain an effective control action sequence directly. Firstly,
      an abstract model of the real environment is extracted. On this basis, a deep
      deterministic policy gradient (DDPG) and a vehicle dynamic model are adopted to
      jointly train a reinforcement learning model, and to decide the optimal
      intelligent driving maneuver. Secondly, the actual scene is transferred to an
      equivalent virtual abstract scene using a transfer model. Furthermore, the
      control action and trajectory sequences are calculated according to the trained
      deep reinforcement learning model. Thirdly, the optimal trajectory sequence is
      selected according to an evaluation function in the real environment. Finally,
      the results demonstrate that the proposed method can deal with the problem of
      intelligent vehicle trajectory planning for continuous input and continuous
      output. The model transfer method improves the model's generalization
      performance. Compared with traditional trajectory planning, the proposed method
      outputs continuous rotation-angle control sequences. Moreover, the lateral
      control errors are also reduced.

PMID- 30200501
TI  - A Sound Source Localisation Analytical Method for Monitoring the Abnormal Night
      Vocalisations of Poultry.
AB  - Due to the increasing scale of farms, it is increasingly difficult for farmers to
      monitor their animals in an automated way. Because of this problem, we focused on
      a sound technique to monitor laying hens. Sound analysis has become an important
      tool for studying the behaviour, health and welfare of animals in recent years. A
      surveillance system using microphone arrays of Kinects was developed for
      automatically monitoring birds' abnormal vocalisations during the night. Based on
      the principle of time-difference of arrival (TDOA) of sound source localisation
      (SSL) method, Kinect sensor direction estimations were very accurate. The system
      had an accuracy of 74.7% in laboratory tests and 73.6% in small poultry group
      tests for different area sound recognition. Additionally, flocks produced an
      average of 40 sounds per bird during feeding time in small group tests. It was
      found that, on average, each normal chicken produced more than 53 sounds during
      the daytime (noon to 6:00 p.m.) and less than one sound at night (11:00 p.m.-3:00
      a.m.). This system can be used to detect anomalous poultry status at night by
      monitoring the number of vocalisations and area distributions, which provides a
      practical and feasible method for the study of animal behaviour and welfare.

PMID- 30200503
TI  - Use of the Wilshire Equations to Correlate and Extrapolate Creep Data of HR6W and
      Sanicro 25.
AB  - Advanced power plant alloys must endure high temperatures and pressures for
      durations at which creep data are often not available, necessitating the
      extrapolation of creep life. Many methods have been proposed to extrapolate creep
      life, and one of recent significance is a set of equations known as the Wilshire
      equations. With this method, multiple approaches can be used to determine creep
      activation energy, increase the goodness of fit of available experimental data,
      and improve the confidence level of calculating long-term creep strength at times
      well beyond the available experimental data. In this article, the Wilshire
      equation is used to extrapolate the creep life of HR6W and Sanicro 25, and
      different methods to determine creep activation energy, region splitting, the use
      of short-duration test data, and the omission of very-short-term data are
      investigated to determine their effect on correlation and calculations. It was
      found that using a known value of the activation energy of lattice self
      diffusion, rather than calculating Q C * from each data set, is both the simplest
      and most viable method to determine Q C * . Region-splitting improved rupture
      time calculations for both alloys. Extrapolating creep life from short-term data
      for these alloys was found to be reasonable.

PMID- 30200500
TI  - The Na/K-ATPase Signaling: From Specific Ligands to General Reactive Oxygen
      Species.
AB  - The signaling function of the Na/K-ATPase has been established for 20 years and
      is widely accepted in the field, with many excellent reports and reviews not
      cited here. Even though there is debate about the underlying mechanism, the
      signaling function is unquestioned. This short review looks back at the evolution
      of Na/K-ATPase signaling, from stimulation by cardiotonic steroids (also known as
      digitalis-like substances) as specific ligands to stimulation by reactive oxygen
      species (ROS) in general. The interplay of cardiotonic steroids and ROS in Na/K
      ATPase signaling forms a positive-feedback oxidant amplification loop that has
      been implicated in some pathophysiological conditions.

PMID- 30200502
TI  - Soybean Bioactive Peptides and Their Functional Properties.
AB  - Soy consumption has been associated with many potential health benefits in
      reducing chronic diseases such as obesity, cardiovascular disease, insulin
      resistance/type II diabetes, certain type of cancers, and immune disorders. These
      physiological functions have been attributed to soy proteins either as intact soy
      protein or more commonly as functional or bioactive peptides derived from soybean
      processing. These findings have led to the approval of a health claim in the USA
      regarding the ability of soy proteins in reducing the risk for coronary heart
      disease and the acceptance of a health claim in Canada that soy protein can help
      lower cholesterol levels. Using different approaches, many soy bioactive peptides
      that have a variety of physiological functions such as hypolipidemic, anti
      hypertensive, and anti-cancer properties, and anti-inflammatory, antioxidant, and
      immunomodulatory effects have been identified. Some soy peptides like lunasin and
      soymorphins possess more than one of these properties and play a role in the
      prevention of multiple chronic diseases. Overall, progress has been made in
      understanding the functional and bioactive components of soy. However, more
      studies are required to further identify their target organs, and elucidate their
      biological mechanisms of action in order to be potentially used as functional
      foods or even therapeutics for the prevention or treatment of chronic diseases.

PMID- 30200505
TI  - Early Fault Diagnosis for Planetary Gearbox Based Wavelet Packet Energy and
      Modulation Signal Bispectrum Analysis.
AB  - The planetary gearbox is at the heart of most rotating machinery. The premature
      failure and subsequent downtime of a planetary gearbox not only seriously affects
      the reliability and safety of the entire rotating machinery but also results in
      severe accidents and economic losses in industrial applications. It is an
      important and challenging task to accurately detect failures in a planetary
      gearbox at an early stage to ensure the safety and reliability of the mechanical
      transmission system. In this paper, a novel method based on wavelet packet energy
      (WPE) and modulation signal bispectrum (MSB) analysis is proposed for planetary
      gearbox early fault diagnostics. First, the vibration signal is decomposed into
      different time-frequency subspaces using wavelet packet decomposition (WPD). The
      WPE is calculated in each time-frequency subspace. Secondly, the relatively high
      energy vectors are selected from a WPE matrix to obtain a reconstructed signal.
      The reconstructed signal is then subjected to MSB analysis to obtain the fault
      characteristic frequency for fault diagnosis of the planetary gearbox. The
      validity of the proposed method is carried out through analyzing the vibration
      signals of the test planetary gearbox in two fault cases. One fault is a chipped
      sun gear tooth and the other is an inner-race fault in the planet gear bearing.
      The results show that the proposed method is feasible and effective for early
      fault diagnosis in planetary gearboxes.

PMID- 30200504
TI  - Gut Bacterial Communities in Geographically Distant Populations of Farmed Sea
      Bream (Sparus aurata) and Sea Bass (Dicentrarchus labrax).
AB  - This study investigated the profile of the autochthonous gut bacterial
      communities in adult individuals of Sparus aurata and Dicentrarchus labrax reared
      in sea cages in five distantly located aquaculture farms in Greece and determine
      the impact of geographic location on them in order to detect the core gut
      microbiota of these commercially important fish species. Data analyses resulted
      in no significant geographic impact in the gut microbial communities within the
      two host species, while strong similarities between them were also present. Our
      survey revealed the existence of a core gut microbiota within and between the two
      host species independent of diet and geographic location consisting of the
      Delftia, Pseudomonas, Pelomonas, Propionibacterium, and Atopostipes genera.

PMID- 30200506
TI  - Parameter Estimation of Lunar Regolith from Lunar Penetrating Radar Data.
AB  - Parameter estimation of the lunar regolith not only provides important
      information about the composition but is also critical to quantifying potential
      resources for lunar exploration and engineering for human outposts. The Lunar
      Penetrating Radar (LPR) onboard China's Chang'E-3 (CE-3) provides a unique
      opportunity for mapping the near-surface stratigraphic structure and estimating
      the parameters of the regolith. In this paper, the electrical parameters and the
      iron-titanium content of regolith are estimated based on the two sets of LPR
      data. Firstly, it is theoretically verified that the relative dielectric constant
      can be estimated according to the difference of the reflected time of two
      receivers from a same target. Secondly, in order to verify the method, a
      parameter estimation flow is designed. Subsequently, a simple model and a complex
      model of regolith are carried out for the method verification. Finally, on the
      basis of the two sets of LPR data, the electrical parameters and the iron
      titanium content of regolith are estimated. The relative dielectric constant of
      regolith at CE-3 landing site is 3.0537 and the content of TiO2 and FeO is
      14.0127%. This helps us predict the reserves of resources at the CE-3 landing
      site and even in the entire Mare Imbrium.

PMID- 30200507
TI  - Special Issue: Fungal Endophytes in Plants.

PMID- 30200509
TI  - Development of a High-Sensitivity Optical Accelerometer for Low-Frequency
      Vibration Measurement.
AB  - Low-frequency vibration is a harmful factor that affects the accuracy of
      micro/nano-measuring machines. Low-frequency vibration cannot be completely
      eliminated by passive control methods, such as the use of air-floating platforms.
      Therefore, low-frequency vibrations must be measured before being actively
      suppressed. In this study, the design of a low-cost high-sensitivity optical
      accelerometer is proposed. This optical accelerometer mainly comprises three
      components: a seismic mass, a leaf spring, and a sensing component based on a
      four-quadrant photodetector (QPD). When a vibration is detected, the seismic mass
      moves up and down due to the effect of inertia, and the leaf spring exhibits a
      corresponding elastic deformation, which is amplified by using an optical lever
      and measured by the QPD. Then, the acceleration can be calculated. The resonant
      frequencies and elastic coefficients of various seismic structures are simulated
      to attain the optimal detection of low-frequency, low-amplitude vibration. The
      accelerometer is calibrated using a homemade vibration calibration system, and
      the calibration experimental results demonstrate that the sensitivity of the
      optical accelerometer is 1.74 V (m.s-2)-1, the measurement range of the
      accelerometer is 0.003-7.29 m.s-2, and the operating frequencies range of 0.4-12
      Hz. The standard deviation from ten measurements is under 7.9 * 10-4 m.s-2. The
      efficacy of the optical accelerometer in measuring low-frequency, low-amplitude
      dynamic responses is verified.

PMID- 30200510
TI  - Traditional Eddy Current-Pulsed Eddy Current Fusion Diagnostic Technique for
      Multiple Micro-Cracks in Metals.
AB  - Due to a harsh working environment, micro-cracks in metal structures (e.g.,
      airplane, oil/gas pipeline, hydro-turbine) often lead to serious accidents, so
      health monitoring of the metals is of great significance to ensure their safe
      operation. However, it is hard to perform quantitative detection of multiple
      micro-cracks by a single nondestructive testing (NDT) technique because of their
      limits. To monitor for multiple micro-cracks in metals, a Traditional Eddy
      Current (TEC) and Pulsed Eddy Current (PEC) fusion NDT technique is proposed in
      this paper. In the proposed technique, the TEC technique is adopted to seek the
      locations of the micro-cracks in the whole of the metal, while the PEC technique
      is adopted to acquire information on the depth of micro-cracks automatically
      according to the location information by the TEC. The experiments indicate that
      the TEC-PEC fusion NDT system can localize the micro-cracks as well as detect the
      micro-cracks quantitatively and automatically; therefore, it can be applied in
      structural health monitoring of metal equipment or in picking candidate
      components in re-manufacturing engineering.

PMID- 30200508
TI  - Gomisin N Alleviates Ethanol-Induced Liver Injury through Ameliorating Lipid
      Metabolism and Oxidative Stress.
AB  - Gomisin N (GN), a lignan derived from Schisandra chinensis, has been shown to
      possess antioxidant, anti-inflammatory, and anticancer properties. In the present
      study, we investigated the protective effect of GN against ethanol-induced liver
      injury using in vivo and in vitro experiments. Histopathological examination
      revealed that GN administration to chronic-binge ethanol exposure mice
      significantly reduced ethanol-induced hepatic steatosis through reducing
      lipogenesis gene expression and increasing fatty acid oxidation gene expression,
      and prevented liver injury by lowering the serum levels of aspartate transaminase
      and alanine transaminase. Further, it significantly inhibited cytochrome P450 2E1
      (CYP2E1) gene expression and enzyme activity, and enhanced antioxidant genes and
      glutathione level in hepatic tissues, which led to decreased hepatic
      malondialdehyde levels. It also lowered inflammation gene expression. Finally, GN
      administration promoted hepatic sirtuin1 (SIRT1)-AMP-activated protein kinase
      (AMPK) signaling in ethanol-fed mice. Consistent with in vivo data, treatment
      with GN decreased lipogenesis gene expression and increased fatty acid oxidation
      gene expression in ethanol-treated HepG2 cells, thereby preventing ethanol
      induced triglyceride accumulation. Furthermore, it inhibited reactive oxygen
      species generation by downregulating CYP2E1 and upregulating antioxidant gene
      expression, and suppressed inflammatory gene expression. Moreover, GN prevented
      ethanol-mediated reduction in SIRT1 and phosphorylated AMPK. These findings
      indicate that GN has therapeutic potential against alcoholic liver disease
      through inhibiting hepatic steatosis, oxidative stress and inflammation.

PMID- 30200511
TI  - Dietary Supplement Use among U.S. Children by Family Income, Food Security Level,
      and Nutrition Assistance Program Participation Status in 2011-2014.
AB  - This analysis characterizes use of dietary supplements (DS) and motivations for
      DS use among U.S. children (<=18 years) by family income level, food security
      status, and federal nutrition assistance program participation using the 2011
      2014 National Health and Nutrition Examination Survey data. About one-third (32%)
      of children used DS, mostly multivitamin-minerals (MVM; 24%). DS and MVM use were
      associated with higher family income and higher household food security level. DS
      use was lowest among children in households participating in the Supplemental
      Nutrition Assistance Program (SNAP; 20%) and those participating in the Special
      Supplemental Nutrition Assistance Program for Women, Infants, and Children (WIC;
      26%) compared to both income-eligible and income-ineligible nonparticipants. Most
      children who used DS took only one (83%) or two (12%) products; although children
      in low-income families took fewer products than those in higher income families.
      The most common motivations for DS and MVM use were to "improve (42% or 46%)" or
      "maintain (34 or 38%)" health, followed by "to supplement the diet (23 or 24%)"
      for DS or MVM, respectively. High-income children were more likely to use DS and
      MVM "to supplement the diet" than middle- or low-income children. Only 18% of
      child DS users took DS based on a health practitioner's recommendation. In
      conclusion, DS use was lower among children who were in low-income or food
      insecure families, or families participating in nutrition assistance programs.

PMID- 30200512
TI  - Characteristics and Temperature Compensation of Non-Dispersive Infrared (NDIR)
      Alcohol Gas Sensors According to Incident Light Intensity.
AB  - This paper discusses the output characteristics of the sensor response of
      infrared ethanol gas detectors based on incident radiation intensity. Sensors
      placed at each focal point of two elliptical waveguides were fabricated to yield
      two module combinations and to verify the output characteristics. A thin Parylene
      C film was deposited onto the reflector surfaces of one module. The thermal
      properties were compared between the sensor (2.0 O) and sensor with a hollow disk
      (1.6 O), the disk being mounted at the end of one detector. The fabricated sensor
      modules were placed inside a gas chamber. The temperature was increased from 253
      K to 333 K, over the concentration range from 0 to 500 ppm. As the temperature
      increases by 10 K, the output of sensor (2.0 O) without and with Parylene-C
      coating typically increased by 70 mV and 52 mV, respectively. However, the sensor
      output with the hollow disk showed an average decrement of 0.8 mV/50 ppm and 1
      mV/50 ppm for module without and with Parylene-C deposition, respectively. For
      concentrations higher than 50 ppm, the estimation error was around +/-5%.
      Further, the sensitivity to temperature variation and the absorbance of infrared
      (IR) reflection was found higher for Parylene-C coated module.

PMID- 30200515
TI  - A Lattice Model for Elastic Particulate Composites.
AB  - In the present article, a version of the lattice or spring network method is
      proposed to model the mechanical response of elastic particulate composites with
      a high volume fraction of spherical particles and with a much weaker matrix
      compared to the stiffness of the particles. The main subject of the article is
      the determination of the axial stiffnesses of the springs of the cell. A
      comparison of the mechanical response of a three-dimensional particulate
      composite cube obtained using the finite element method and the proposed
      methodology showed that the efficiency of the proposed methodology increases with
      an increasing volume fraction of the particles.

PMID- 30200513
TI  - Respiratory Bordetella bronchiseptica Carriage is Associated with Broad
      Phenotypic Alterations of Peripheral CD4+CD25+ T Cells and Differentially Affects
      Immune Responses to Secondary Non-Infectious and Infectious Stimuli in Mice.
AB  - The respiratory tract is constantly exposed to the environment and displays a
      favorable niche for colonizing microorganisms. However, the effects of
      respiratory bacterial carriage on the immune system and its implications for
      secondary responses remain largely unclear. We have employed respiratory carriage
      with Bordetella bronchiseptica as the underlying model to comprehensively address
      effects on subsequent immune responses. Carriage was associated with the
      stimulation of Bordetella-specific CD4+, CD8+, and CD4+CD25+Foxp3+ T cell
      responses, and broad transcriptional activation was observed in CD4+CD25+ T
      cells. Importantly, transfer of leukocytes from carriers to acutely B.
      bronchiseptica infected mice, resulted in a significantly increased bacterial
      burden in the recipient's upper respiratory tract. In contrast, we found that
      respiratory B. bronchiseptica carriage resulted in a significant benefit for the
      host in systemic infection with Listeria monocytogenes. Adaptive responses to
      vaccination and influenza A virus infection, were unaffected by B. bronchiseptica
      carriage. These data showed that there were significant immune modulatory
      processes triggered by B. bronchiseptica carriage, that differentially affect
      subsequent immune responses. Therefore, our results demonstrated the complexity
      of immune regulation induced by respiratory bacterial carriage, which can be
      beneficial or detrimental to the host, depending on the pathogen and the
      considered compartment.

PMID- 30200514
TI  - Antiviral Activity of Fermented Ginseng Extracts against a Broad Range of
      Influenza Viruses.
AB  - Ginseng products used as herb nutritional supplements are orally consumed and
      fermented to ginsenoside compounds by the intestinal microbes. In this study, we
      investigated antiviral protective effects of fermented ginseng extracts against
      different strains of influenza viruses in genetically diverse mouse models.
      Intranasal coinoculation of mice with fermented ginseng extract and influenza
      virus improved survival rates and conferred protection against H1N1, H3N2, H5N1,
      and H7N9 strains, with the efficacy dependent on the dose of ginseng samples.
      Antiviral protection by fermented ginseng extract was observed in different
      genetic backgrounds of mice and in the deficient conditions of key adaptive
      immune components (CD4, CD8, B cell, MHCII). The mice that survived primary virus
      inoculation with fermented ginseng extract developed immunity against the
      secondary infection with homologous and heterosubtypic viruses. In vitro cell
      culture experiments showed moderate virus neutralizing activity by fermented
      ginseng extract, probably by inhibiting hemagglutination and neuraminidase
      activity. This study suggests that fermented ginseng extracts might provide a
      means to treat influenza disease regardless of virus strains.

PMID- 30200520
TI  - Effect of Heat Treatment on the Properties of Wood-Derived Biocarbon Structures.
AB  - Wood-derived porous graphitic biocarbons with hierarchical structures were
      obtained by high-temperature (2200-2400  degrees C) non-catalytic graphitization,
      and their mechanical, electrical and thermal properties are reported for the
      first time. Compared to amorphous biocarbon produced at 1000  degrees C, the
      graphitized biocarbon-2200  degrees C and biocarbon-2400  degrees C exhibited
      increased compressive strength by ~38% (~36 MPa), increased electrical
      conductivity by ~8 fold (~29 S/cm), and increased thermal conductivity by ~5 fold
      (~9.5 W/(m.K) at 25  degrees C). The increase of duration time at 2200  degrees C
      contributed to increased thermal conductivity by ~12%, while the increase of
      temperature from 2200 to 2400  degrees C did not change their thermal
      conductivity, indicating that 2200  degrees C is sufficient for non-catalytic
      graphitization of wood-derived biocarbon.

PMID- 30200516
TI  - Heat Shock Proteins in Alzheimer's Disease: Role and Targeting.
AB  - Among diseases whose cure is still far from being discovered, Alzheimer's disease
      (AD) has been recognized as a crucial medical and social problem. A major issue
      in AD research is represented by the complexity of involved biochemical pathways,
      including the nature of protein misfolding, which results in the production of
      toxic species. Considering the involvement of (mis)folding processes in AD
      aetiology, targeting molecular chaperones represents a promising therapeutic
      perspective. This review analyses the connection between AD and molecular
      chaperones, with particular attention toward the most important heat shock
      proteins (HSPs) as representative components of the human chaperome: Hsp60, Hsp70
      and Hsp90. The role of these proteins in AD is highlighted from a biological
      point of view. Pharmacological targeting of such HSPs with inhibitors or
      regulators is also discussed.

PMID- 30200519
TI  - The Golden Activity of Lysinibacillus sphaericus: New Insights on Gold
      Accumulation and Possible Nanoparticles Biosynthesis.
AB  - Power struggles surrounding the increasing economic development of gold mining
      give rise to severe environmental and social problems. Two new strains of
      Lysinibacillus sphaericus were isolated from an area of active alluvial gold
      mining exploitation at El Bagre, Antioquia. The absorption capacity of these
      strains and some of the L. sphaericus Microbiological Research Center (CIMIC)
      collection (CBAM5, OT4b.31, III(3)7) were evaluated by spectrophotometry
      according to a calibration gold curve of HAuCl4- with concentrations between 0
      ug/mL and 100 ug/mL. Bioassays with living biomass were carried out with an
      initial gold concentration of 60 ug/mL. Their sorption capacity was evident,
      reaching percentages of gold removal between 25% and 85% in the first 2 h and 75%
      to 95% after 48 h. Biosynthesis of possible gold nanoparticles (AuNPs) in assays
      with living biomass was also observed. Metal sorption was evaluated using
      scanning electron microscopy and energy-dispersive X-ray spectroscopy (EDS)
      analysis. The sorption and fabrication capacity exhibited by the evaluated
      strains of L. sphaericus converts this microorganism into a potential alternative
      for biomining processes, especially those related to gold extraction.

PMID- 30200517
TI  - Fungal Resistance to Echinocandins and the MDR Phenomenon in Candida glabrata.
AB  - Candida glabrata has thoroughly adapted to successfully colonize human mucosal
      membranes and survive in vivo pressures. prior to and during antifungal
      treatment. Out of all the medically relevant Candida species, C. glabrata has
      emerged as a leading cause of azole, echinocandin, and multidrug (MDR: azole +
      echinocandin) adaptive resistance. Neither mechanism of resistance is intrinsic
      to C. glabrata, since stable genetic resistance depends on mutation of drug
      target genes, FKS1 and FKS2 (echinocandin resistance), and a transcription
      factor, PDR1, which controls expression of major drug transporters, such as CDR1
      (azole resistance). However, another hallmark of C. glabrata is the ability to
      withstand drug pressure both in vitro and in vivo prior to stable "genetic
      escape". Additionally, these resistance events can arise within individual
      patients, which underscores the importance of understanding how this fungus is
      adapting to its environment and to drug exposure in vivo. Here, we explore the
      evolution of echinocandin resistance as a multistep model that includes general
      cell stress, drug adaptation (tolerance), and genetic escape. The extensive
      genetic diversity reported in C. glabrata is highlighted.

PMID- 30200521
TI  - Influence of Dlutaraldehyde Cross-Linking Modes on the Recyclability of
      Immobilized Lipase B from Candida antarctica for Transesterification of Soy Bean
      Oil.
AB  - Lipase B from Candida antarctica (CAL-B) is largely employed as a biocatalyst for
      hydrolysis, esterification, and transesterification reactions. CAL-B is a good
      model enzyme to study factors affecting the enzymatic structure, activity and/or
      stability after an immobilization process. In this study, we analyzed the
      immobilization of CAL-B enzyme on different magnetic nanoparticles, synthesized
      by the coprecipitation method inside inverse micelles made of zwitterionic
      surfactants, with distinct carbon chain length: 4 (ImS4), 10 (ImS10) and 18
      (ImS18) carbons. Magnetic nanoparticles ImS4 and ImS10 were shown to cross-link
      to CAL-B enzyme via a Michael-type addition, whereas particles with ImS18 were
      bond via pyridine formation after glutaraldehyde cross-coupling. Interestingly,
      the Michael-type cross-linking generated less stable immobilized CAL-B, revealing
      the influence of a cross-linking mode on the resulting biocatalyst behavior.
      Curiously, a direct correlation between nanoparticle agglomerate sizes and CAL-B
      enzyme reuse stability was observed. Moreover, free CAL-B enzyme was not able to
      catalyze transesterification due to the high methanol concentration; however, the
      immobilized CAL-B enzyme reached yields from 79.7 to 90% at the same conditions.
      In addition, the transesterification of lipids isolated from oleaginous yeasts
      achieved 89% yield, which confirmed the potential of immobilized CAL-B enzyme in
      microbial production of biodiesel.

PMID- 30200522
TI  - Effectiveness of Sensors Contact Metallization (Ti, Au, and Ru) and
      Biofunctionalization for Escherichia coli Detection.
AB  - In designing a bacteria biosensor, various issues must be addressed: the
      specificity of bacteria recognition, the immobilization of biomolecules that act
      as the bacteria receptor, and the selectivity of sensor surface. The aim of this
      paper was to examine how the biofunctionalized surface of Ti, Au, and Ru metals
      reacts in contact with strains of Escherichia coli (E. coli). The focus on metal
      surfaces results from their future use as electrodes in high frequency
      biosensors, e.g., resonant circuits or transmission-line sections. First, the
      surfaces of different metals were chemically functionalized with 3
      aminopropyltriethoxysilane (APTES) and glutaraldehyde or with 3
      glycidylooxypropyltrimethoxysilane (GPTMS) followed by N-(5-amino-1
      carboxypentyl) iminodiacetic acid (AB-NTA) and NiCl2. Secondly, the
      lipopolysaccharide binding protein (LBP), polyclonal anti-Escherichia coli
      antibody and bacteriophage protein gp37 were tested as bacteria receptors. The
      selectivity and specificity have been confirmed by the Enzyme-Linked
      Immunosorbent Assay (ELISA) and visualized by scanning electron microscopy at low
      landing energies. We noticed that LBP, polyclonal antibody, and gp37 were
      successfully immobilized on all studied metals and recognized the E. coli
      bacteria selectively. However, for the antibody, the highest reactivity was
      observed when Ti surface was modified, whereas the bacteria binding was
      comparable between LBP and gp37 on the functionalized Ru surfaces, independent
      from modification. Thus, all surfaces were biocompatible within the scope of
      biosensor functionality, with titanium functionalization showing the best
      performance.

PMID- 30200518
TI  - Genetic Renal Diseases: The Emerging Role of Zebrafish Models.
AB  - The structural and functional similarity of the larval zebrafish pronephros to
      the human nephron, together with the recent development of easier and more
      precise techniques to manipulate the zebrafish genome have motivated many
      researchers to model human renal diseases in the zebrafish. Over the last few
      years, great advances have been made, not only in the modeling techniques of
      genetic diseases in the zebrafish, but also in how to validate and exploit these
      models, crossing the bridge towards more informative explanations of disease
      pathophysiology and better designed therapeutic interventions in a cost-effective
      in vivo system. Here, we review the significant progress in these areas giving
      special attention to the renal phenotype evaluation techniques. We further
      discuss the future applications of such models, particularly their role in
      revealing new genetic diseases of the kidney and their potential use in
      personalized medicine.

PMID- 30200523
TI  - Nitrate Accumulation and Expression Patterns of Genes Involved in Nitrate
      Transport and Assimilation in Spinach.
AB  - Excessive accumulation of nitrate in spinach is not only harmful to human beings,
      but also limits the efficiency of nitrogen usage. However, the underlying
      mechanism of nitrate accumulation in plants remains unclear. This study analyzed
      the physiological and molecular characteristics of nitrate uptake and
      assimilation in the spinach varieties with high or low nitrate accumulation. Our
      results showed that the variety of spinach with a high nitrate content (So18) had
      higher nitrate uptake compared to the variety with a low nitrate content (So10).
      However, the nitrate reductase activities of both varieties were similar, which
      suggests that the differential capacity to uptake and transport nitrate may
      account for the differences in nitrate accumulation. The quantitative PCR
      analysis showed that there was a higher level of expression of spinach nitrate
      transporter (SoNRT) genes in So18 compared to those in So10. Based on the
      function of Arabidopsis homologs AtNRTs, the role of spinach SoNRTs in nitrate
      accumulation is discussed. It is concluded that further work focusing on the
      expression of SoNRTs (especially for SoNRT1.4, SoNRT1.5 and SoNRT1.3) may help us
      to elucidate the molecular mechanism of nitrate accumulation in spinach.

PMID- 30200524
TI  - TiO2-KH550 Nanoparticle-Reinforced PVA/xylan Composite Films with Multifunctional
      Properties.
AB  - In order to improve the strength of polyvinyl alcohol (PVA)/xylan composite films
      and endow them with ultraviolet (UV) shielding ability, TiO2-KH550 nanoparticles
      was synthesized and added into the PVA/xylan matrix. The TiO2-KH550 nanoparticle
      dispersed well in the 0.04% sodium hexametaphosphate (SHMP) solution under
      ultrasonic and stirring treatments. Investigations on the properties of the films
      showed that TiO2-KH550 had the positive impact on improving the strength,
      moisture, and oxygen barrier properties of the composite films. The maximum
      tensile strength (27.3 MPa), the minimum water vapor permeability (2.75 * 10-11
      g.m-1.s-1.Pa-1), and oxygen permeability (4.013 cm3.m-2.24 h-1.0.1MPa-1) were
      obtained under the addition of 1.5% TiO2-KH550. The tensile strength of TiO2
      KH550 reinforced composite film was increased by 70% than that of the pure
      PVA/xylan composite film, and the water vapor and oxygen permeability were
      decreased by 31% and 41%, respectively. Moreover, the UV transmittance of the
      film at the wavelength of 400 nm was almost zero when adding ~1.5~2.5% (weight
      ratio, based on the total weight of PVA and xylan) of TiO2-KH550, which indicated
      the PVA/xylan composite films were endowed with an excellent UV light shielding
      ability.

PMID- 30200525
TI  - Who Needs Neighbors? PKS8 Is a Stand-Alone Gene in Fusarium graminearum
      Responsible for Production of Gibepyrones and Prolipyrone B.
AB  - Genome sequencing of the genus Fusarium has revealed a great capacity for
      discovery of new natural products of potential economical and therapeutic
      importance. Several of these are unknown. In this study, we investigated the
      product of the PKS8 gene in Fusarium graminearum, which was recently linked to
      gibepyrones in F. fujikuroi. Genomic analyses showed that PKS8 constitutes a
      stand-alone gene in F. graminearum and related species. Overexpression of PKS8
      resulted in production of gibepyrones A, B, D, G and prolipyrone B, which could
      not be detected in the wild type strain. Our results suggest that PKS8 produces
      the entry compound gibepyrone A, which is subsequently oxidized by one or several
      non-clustering cytochrome P450 monooxygenases ending with prolipyrone B.

PMID- 30200526
TI  - Development of a Sensitive Enzyme-Linked Immunosorbent Assay and Rapid Gold
      Nanoparticle Immunochromatographic Strip for Detecting Citrinin in Monascus
      Fermented Food.
AB  - Antibodies against citrinin (CTN) were generated from rabbits, which were
      injected with CTN-keyhole limpet hemocyanin (KLH). This work involved the
      development of a sensitive competitive direct enzyme-linked immunosorbent assay
      (cdELISA) and a rapid gold nanoparticle immunochromatographic strip (immunostrip)
      method for analyzing CTN in Monascus-fermented food. CTN at a concentration of
      5.0 ng/mL caused 50% inhibition (IC50) of CTN-horseradish peroxidase (CTN-HRP)
      binding to the antibodies in the cdELISA. The capable on-site detection of CTN
      was accomplished by a rapid antibody-gold nanoparticle immunostrip with a
      detection limit of 20 ng/mL and that was completed within 15 min. A close
      inspection of 19 Monascus-fermented foods by cdELISA confirmed that 14 were
      contaminated with citrinin at levels from 28.6-9454 ng/g. Further analysis with
      the immunostrip is consistent with those results obtained using cdELISA. Both
      means are sensitive enough for the rapid examination of CTN in Monascus-fermented
      food products.

PMID- 30200527
TI  - Inhibition of Lipid Peroxidation of Kiwicha (Amaranthus caudatus) Hydrolyzed
      Protein Using Zebrafish Larvae and Embryos.
AB  - Amaranth protein concentrate (APC) was hydrolyzed under in vitro gastrointestinal
      conditions. APC proteins were partially degraded by pepsin at pHs 1.2, 2.0, and
      3.2. During the intestinal phase (pepsin/pancreatin enzymes at pH 7.0), no
      polypeptide bands were observed in the gel, suggesting the susceptibility of
      amaranth proteins to the action of digestive enzymes. The potent in vitro
      inhibition of lipid peroxidation, shown by the gastric and intestinal digests,
      was confirmed in the zebrafish larvae, with a 72.86% reduction in oxidation of
      lipids in the presence of the gastric hydrolysate at pH 2.0, compared to a 95.72%
      reduction in the presence of the gastrointestinal digest. APC digests were
      capable of reducing reactive oxygen species (ROS) production in the zebrafish
      embryo model with a value of fluorescence of 52.5% for the gastric hydrolysate,
      and 48.4% for the intestinal hydrolysate.

PMID- 30200529
TI  - Study on Nonlinear Conductivity of CCTO/EPDM Rubber Composites.
AB  - Researches of the theories and application of polymer composites with nonlinear
      conductivity are useful for dealing with the nonuniform electrical fields widely
      existing in the cable accessory insulation. In the present work, we fabricated
      CCTO (CaCu3Ti4O12)/EPDM (Ethylene Propylene Diene Monomer) composites and
      investigated their breakdown strength, dielectric and nonlinear conductivity
      properties in detail; the microstructures of fillers and composites were
      characterized by scanning electron microscopy (SEM) and X-ray diffraction. CCTO
      particles are uniformly dispersed in CCTO/EPDM composites, and the composites
      showed nonlinear conductivity with electric field changes. When the CCTO particle
      content is low, the conductivity of CCTO/EPDM composites does not present obvious
      nonlinearity. However, when CCTO content exceeds 2 vol %, the conductivity
      experiences a nonlinear change with increasing electric field strength and the
      threshold field (Eth) of nonlinear conductivity declines with the increase of
      CCTO contents. In addition, it can be found from experiment and simulation
      results that 8 vol % CCTO/EPDM exhibit significant nonlinear conductivity and
      dielectric properties as expected, and homogenizing the electrical field much
      more effectively. Therefore, this paper offers a preliminary discussion about the
      variation trend of nonlinear conductivity CCTO/EDPM composites, providing an
      effective reference to solve the application of nonlinear conductivity materials
      for cable accessories.

PMID- 30200528
TI  - Immunogenicity of a Tripartite Cell Penetrating Peptide Containing a MUC1
      Variable Number of Tandem Repeat (VNTR) and A T Helper Epitope.
AB  - Peptide-based vaccines for cancer have many advantages however, for optimization
      these immunogens should incorporate peptide epitopes that induce CD8, as well as
      CD4 responses, antibody and long term immunity. Cell penetrating peptides (CPP)
      with a capacity of cytosolic delivery have been used to deliver antigenic
      peptides and proteins to antigen presenting cells to induce cytotoxic T cell,
      helper T cell and humoral responses in mice. For this study, a tripartite CPP
      including a mucin 1 (MUC1) variable number of tandem repeat (VNTR) containing
      multiple T cell epitopes and tetanus toxoid universal T helper epitope peptide
      (tetCD4) was synthesised (AntpMAPMUC1tet) and immune responses investigated in
      mice. Mice vaccinated with AntpMAPMUC1tet + CpG show enhanced antigen-specific
      interferon-gamma (IFN-gamma) and IL-4 T cell responses compared with
      AntpMAPMUC1tet vaccination alone and induced a Th1 response, characterised by a
      higher ratio of IgG2a antibody/IgG1 antibodies. Furthermore, vaccination
      generated long term MUC1-specific antibody and T cell responses and delayed
      growth of MUC1+ve tumours in mice. This data demonstrates the efficient delivery
      of branched multiple antigen peptides incorporating CPP and that the addition of
      CpG augments immune responses.

PMID- 30200530
TI  - Sporothrix schenckii Cell Wall Proteins-Stimulated BMDCs Are Able to Induce a Th1
      Prone Cytokine Profile In Vitro.
AB  - Sporotrichosis is a subcutaneous mycosis affecting humans and other animals. The
      disease can be acquired by accidental inoculation of the fungus through the skin
      or through the respiratory system. Sporotrichosis can also be transmitted through
      bites or scratches by infected cats and more rarely by other animals (zoonotic
      transmission). Conventional antifungal therapy is especially inefficient in
      immunocompromised patients, who tend to develop the most severe forms of the
      disease, thus prompting the search for alternative therapies. Given their antigen
      presenting properties, dendritic cells (DCs) have been used in both prophylactic
      and therapeutic vaccination strategies. Hence, this study aims to assess the use
      of DCs as a prophylactic tool in sporotrichosis by evaluating the immune profile
      induced by Sporothrix schenckii cell wall proteins (SsCWP)-stimulated, bone
      marrow-derived DCs (BMDCs). Mouse BMDCs were stimulated with SsCWP for 24 h and
      analyzed for the surface expression of costimulatory molecules and TLR-4, as well
      as for the secretion of proinflammatory cytokines and IL-10. Following that,
      activated BMDCs were cocultured with splenocytes for 72 h and had the same
      cytokines measured in the supernatant. SsCWP-stimulated BMDCs showed higher
      expression of CD80, CD86, and CD40, but not TLR-4, and higher secretion of IL-6,
      IL-17A, and TNF. On the other hand, higher levels of IFN-gamma, IL-10, and IL-2
      were found in the supernatants of the coculture as compared with the BMDCs alone;
      TNF secretion was almost completely abrogated, whereas IL-6 was only partially
      inhibited and IL-17A was unaffected. Our results thus suggest that SsCWP
      stimulated BMDCs are able to induce a Th1-prone cytokine profile which is known
      to be protective against other fungal diseases. This result could lead to studies
      which evaluate the development of prophylactic and/or therapeutic DC-based tools
      against sporotrichosis.

PMID- 30200531
TI  - Contaminants in Grain-A Major Risk for Whole Grain Safety?
AB  - Grains are the main energy and carbohydrate sources for human nutrition globally.
      Governmental and non-governmental authorities recommend whole grains as a healthy
      food choice. The role of contaminants in (whole) grains and how to mitigate any
      potential risk following their consumption has not been reported. With this
      narrative review, we shed light on the potential human health risk from
      contaminants in whole grains and elaborate strategies to mitigate such risk. We
      found that grains represent a significant source of food-borne contaminants, the
      main ones being; mycotoxins including (A) aflatoxin B1; (B) ochratoxin A; (C)
      fumonisin B1; (D) deoxynivalenol; (E) zearalenone; toxic metals like arsenic,
      cadmium and lead; as well as process contaminants such as acrylamide. Whole
      grains usually contain more contaminants than refined products. However, whole
      grains also provide more nutrients that may reduce the impact of these
      contaminants. Strict regulatory thresholds aim to minimize the risk of
      contaminants to public health. The consumer can further impact on the mitigation
      of any risk by eating a healthy diet filled with nutrient-dense foods such as
      whole grains and probiotics. The risk posed by contaminants from whole grains do
      not outweigh the known nutritional benefits of whole grain consumption.

PMID- 30200532
TI  - Fermented Dessert with Whey, Ingredients from the Peel of Jabuticaba (Myrciaria
      cauliflora) and an Indigenous Culture of Lactobacillus plantarum: Composition,
      Microbial Viability, Antioxidant Capacity and Sensory Features.
AB  - The use of agro-industrial wastes in combination with indigenous lactic acid
      bacteria is an interesting option to confer functional potential to food
      products. The microbial viability, chemical composition, antioxidant capacity,
      texture and sensory acceptability of a fermented dairy dessert containing the
      indigenous culture Lactobacillus plantarum CNPC003, whey and ingredients obtained
      from the jabuticaba (Myrciaria cauliflora) peel were compared with formulations
      without lactobacilli (control) or containing a commercial probiotic culture
      (Lactobacillus rhamnosus LR32). L. plantarum presented viability higher than 7
      log CFU g-1 in the dessert, as did the commercial probiotic, for 21 days at 4 +/-
      1  degrees C. Total phenolic contents (45-60 mg gallic acid equivalents, GAE, 100
      g-1) were comparable to those of other studies evaluating dairy products
      containing plant sources. The formulations were low in fat, presenting as
      acceptable for overall consumption, with attractive color and appreciable
      texture. Considering the total antioxidant capacity, 200-250 g of dessert would
      be necessary to capture 1 g of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals. The
      dessert with Lactobacillus plantarum CNPC003 is seen as a viable alternative for
      the use of whey and jabuticaba peel, as well as a potential functional food due
      to the concentration of lactobacilli reached, besides the presence of antioxidant
      phenolic compounds.

PMID- 30200533
TI  - Imidazolium Chloride: An Efficient Catalyst for Transamidation of Primary Amines.
AB  - A highly efficient and convenient protocol of imidazolium chloride (30 mol %)
      catalyzed amidation of amines with moderate to excellent yields was reported. The
      protocol shows broad substrate scope for aromatic, aliphatic, and heterocyclic
      primary amines.

PMID- 30200535
TI  - DroneTank: Planning UAVs' Flights and Sensors' Data Transmission under Energy
      Constraints.
AB  - We consider an Unmanned Aerial Vehicle (UAV, also known as drone) as an aerial
      sink to travel along a natural landscape or rural industrial linear
      infrastructure to collect data from deployed sensors. We study a joint schedule
      problem that involves flight planning for the drone and transmission scheduling
      for sensors, such that the maximum amount of data can be collected with a limited
      individual energy budget for the UAV and the sensors, respectively. On one hand,
      the flight planning decides the flight speed and flight path based on sensor
      locations, energy budgets, and the transmission schedule. On the other hand, the
      transmission schedule decides for each sensor when to deliver data and what
      transmission power to use based on the energy budgets and flight plan. By
      observing three import optimality properties, we decouple the joint problem into
      two subproblems: drone flight planning and sensor transmission scheduling. For
      the first problem, we propose a dynamic programming algorithm to produce the
      optimal flight planning. For the second problem, with a flight plan as input, we
      introduce a novel technique (water-tank), which together with dynamic
      programming, is the key to achieve an optimal transmission schedule that
      maximizes data collection. Simulations show that the separately determined flight
      plan and transmission schedule are near-optimal for the original joint problem.

PMID- 30200534
TI  - Knowledge, Attitudes and Practices Regarding Diabetes in the General Population:
      A Cross-Sectional Study from Pakistan.
AB  - Background: Low knowledge about diabetes risk factors coupled with high disease
      prevalence is common in low-resource countries. This study evaluated diabetes
      related knowledge, attitudes, and practices in the general population in Punjab
      (Pakistan). Methods: A cross-sectional study was conducted in five districts in
      Punjab from January to March 2017. Data were collected from 2019 adults aged 18
      90 years through face-to-face interviews using a semi-structured questionnaire.
      The total knowledge score ranged from 0-9; a score >=6 was considered adequate
      diabetes awareness. Descriptive statistics, chi-square tests, and linear and
      binary logistic regression were used for the analyses. Results: Respondents' mean
      age was 32.92 +/- 11.4 years. In total, 85.9% of respondents had heard of
      diabetes, and 30.1% knew about the glucose tolerance test. We found 2.3% of
      respondents scored zero for diabetes knowledge, 11.3% scored 9, and 47.4% scored
      >=6 (adequate awareness). Being female (beta = 0.37, 95% confidence interval
      [CI]: 0.16, 0.05; p = 0.001), socioeconomic status (beta = 0.24, 95% CI: 0.12,
      0.36; p < 0.001), being diabetic (beta = 0.82, 95% CI: 0.53, 1.10; p < 0.001),
      and higher education (beta = 0.25, 95% CI: 0.17, 0.33; p < 0.001) were
      significantly associated with knowledge score. Respondents with high
      socioeconomic status showed significantly higher positive attitudes compared with
      those with low socioeconomic status (adjusted odds ratio 1.57, 95% CI: 1.12,
      2.24). Only 8.7% (30/343) of those diagnosed with diabetes had never undergone
      blood glucose screening since diagnosis. Conclusions: Knowledge of diabetes risk
      factors, management, and care is low in Pakistan's general population. Targeted
      public education programs should be instigated at a national level to increase
      understanding of diabetes prevention and treatment.

PMID- 30200537
TI  - Strain Rate Sensitivity of Tensile Properties in Ti-6.6Al-3.3Mo-1.8Zr-0.29Si
      Alloy: Experiments and Constitutive Modeling.
AB  - The complex deformation usually involves wide strain-rate change. However, few
      efforts have been devoted to investigate the effect of strain rate history on the
      tensile behavior of alpha + beta titanium alloy. In present paper, tensile tests
      of Ti-6.6Al-3.3Mo-1.8Zr-0.29Si alloy were carried out under both constant and
      variable strain-rate conditions within the region from 10-3~500 s-1. A single
      stress pulse experimental technique was utilized to conduct the recovery tests.
      The strain-rate history effect was examined. It is found that the flow stress is
      independent on the strain rate history, though the alloy exhibits obvious
      positive strain rate sensitivity. The Taylor-Quinney coefficient of the plastic
      work converted to heat is proved as 0.9 at high strain rates. The cavitation
      fracture mechanism is revealed by microstructural observation over the full range
      explored. In basis of the experimental results and other pulished literatures,
      empirical Khan-Huang-Liang constitutive model was suitably modified to account
      for the strain-rate dependent behavior. Good agreement is achieved between the
      modeling prediction results and experimental data.

PMID- 30200536
TI  - PSEN1 p.Thr116Ile Variant in Two Korean Families with Young Onset Alzheimer's
      Disease.
AB  - An in depth study of PSEN1 mutation p.Thr116Ile (c.335C>T) is presented from two
      Korean families with autosomal dominant inheritance. Clinical manifestation of
      our patients included memory loss, attention deficits, visuospatial dysfunction,
      agnosia, aphasia, apraxia, and personality changes, which occurred in their 30s.
      PSEN1 Thr116Ile was initially discovered in an Italian patient and two French
      families with early onset Alzheimer's disease (EOAD) with similar age of onset.
      To verify the possible pathogenic mechanisms of mutation, in silico predictions
      and 3D modeling were performed. Structure predictions revealed significant
      aberrations in first hydrophilic loop (HL-I loop). The hydrophobic isoleucine
      could alter the loop orientation through increased hydrophobic contacts with the
      surrounding amino acids. Mutation could destroy a possible hydrogen bond between
      tyrosine 115 and threonine 116, which may affect the loop conformation. HL-I was
      confirmed as a conservative region of PSEN1, which may be critical in PSEN1
      functions. An additional pathogenic mutation, PSEN1 Thr116Asn, was also found for
      the same residue, where the patient presented young onset AD (YOND). Other
      mutations in HL-I loop, such as Tyr115His and Glu120Asp, were described in
      patients with YOND, supporting the critical role of HL-I loop in PSEN1 activity.

PMID- 30200538
TI  - Simultaneous Determination of Chlorogenic Acid Isomers and Metabolites in Rat
      Plasma Using LC-MS/MS and Its Application to A Pharmacokinetic Study Following
      Oral Administration of Stauntonia Hexaphylla Leaf Extract (YRA-1909) to Rats.
AB  - Stauntonia hexaphylla leaf extract (YRA-1909), which is widely used for the
      antirheumatic properties, has been under phase 2 clinical trials in patients with
      rheumatoid arthritis since April 2017. Liquid chromatography-tandem mass
      spectrometric method while using liquid-liquid extraction with ethyl acetate was
      validated for the simultaneous determination of the major active components of
      YRA-1909, including chlorogenic acid (CGA), neochlorogenic acid (NCGA),
      cryptochlorogenic acid (CCGA), and their metabolites (i.e., caffeic acid (CA),
      caffeic acid 3-O-glucuronide (CA-3-G), caffeic acid 4-O-glucuronide (CA-4-G), and
      ferulic acid (FA)) in rat plasma and applied to a pharmacokinetic study of YRA
      1909 in rats. Seven analytes were separated on Halo C18 while using gradient
      elution of formic acid and methanol, and then quantified in selected reaction
      monitoring mode whle using negative electrospray ionization. Following oral
      administration of YRA-1909 at doses of 25, 50, and 100 mg/kg to male Sprague
      Dawley rats, CGA, NCGA, and CCGA were rapidly absorbed and metabolized to CA, CA
      3-G, and CA-4-G. The area under the plasma concentration-time curve (AUClast) of
      CGA, NCGA, CCGA, and three metabolites linearly increased as the YRA-1909 dose
      increased. Other pharmacokinetic parameters were comparable among three doses
      studied. AUClast values for CA, CA-3-G, and CA-4-G exceeded those for CGA, NCGA,
      and CCGA.

PMID- 30200540
TI  - Finite Element Analysis for the Self-Loosening Behavior of the Bolted Joint with
      a Superelastic Shape Memory Alloy.
AB  - A macroscopic constitutive model is proposed in this research to reproduce the
      uniaxial transition ratcheting behaviors of the superelastic shape memory alloy
      (SMA) undergoing cyclic loading, based on the cosine-type phase transition
      equation with the initial martensite evolution coefficient that provides the
      predictive residual martensite accumulation evolution and the nonlinear feature
      of hysteresis loop. The calculated results are compared with the experimental
      results to show the validity of the present computational procedure in transition
      ratcheting. Finite element implementation for the self-loosening behavior of the
      superelastic SMA bolt is then carried out based on the proposed constitutive
      model to analyze the curves of stress-strain responses on the bolt bar, clamping
      force reduction law, dissipation energy change law of the bolted joint for
      different external loading cases, and preload force of the bolt.

PMID- 30200541
TI  - Pre-Service Teachers' Intervention in School Bullying Episodes with Special
      Education Needs Students: A Research in Italian and Greek Samples.
AB  - Background: The aim of the study was to compare the level of self-confidence in
      dealing with problems at school, the attitude towards bullying situations and the
      recommended strategies to cope with bullying in two samples of pre-service
      teachers (PSTs). The PSTs were in training to become teachers with special
      education needs students (SEN) and came from two different countries (Italy and
      Greece). Methods: A questionnaire survey was made involving 110 Italian and 84
      Greek PSTs. Results: The results about self-confidence showed that Greek PSTs had
      lower outcome expectations and a higher external locus of causality than Italian
      PSTs. Teachers' training programs and school preventive intervention were also
      discussed. Conclusions: Because the participants in this investigation will be
      teachers in the near future, they require specific training on bullying in
      general and in students with SEN in particular.

PMID- 30200542
TI  - Phosphorescent Modulation of Metallophilic Clusters and Recognition of Solvents
      through a Flexible Host-Guest Assembly: A Theoretical Investigation.
AB  - MP2 (Second order approximation of Moller-Plesset perturbation theory) and DFT/TD
      DFT (Density functional theory/Time-dependent_density_functional_theory)
      investigations have been performed on metallophilic nanomaterials of host
      clusters [Au(NHC)2]+???[M(CN)2]-???[Au(NHC)2]+ (NHC = N-heterocyclic carbene, M =
      Au, Ag) with high phosphorescence. The phosphorescence quantum yield order of
      clusters in the experiments was evidenced by their order of MUS1/DeltaES1-T1
      values ( MU S 1 : S0 -> S1 transition dipole, ? E S 1 - T 1 : splitting energy
      between the lowest-lying singlet S1 and the triplet excited state T1 states). The
      systematic variation of the guest solvents (S1: CH3OH, S2: CH3CH2OH, S3: H2O) are
      employed not only to illuminate their effect on the metallophilic interaction and
      phosphorescence but also as the probes to investigate the recognized capacity of
      the hosts. The simulations revealed that the metallophilic interactions are
      mainly electrostatic and the guests can subtly modulate the geometries,
      especially metallophilic Au???M distances of the hosts through mutual hydrogen
      bond interactions. The phosphorescence spectra of hosts are predicted to be blue
      shifted under polar solvent and the excitation from HOMO (highest occupied
      molecular orbital) to LUMO (lowest unoccupied molecular orbital) was found to be
      responsible for the 3MLCT (triplet metal-to-ligand charge transfer) characters in
      the hosts and host-guest complexes. The results of investigation can be
      introduced as the clues for the design of promising blue-emitting phosphorescent
      and functional materials.

PMID- 30200544
TI  - Compact Multilayer Yagi-Uda Based Antenna for IoT/5G Sensors.
AB  - To increase the capacity and performance of communication systems, the new
      generation of mobile communications (5G) will use frequency bands in the mmWave
      region, where new challenges arise. These challenges can be partially overcome by
      using higher gain antennas, Multiple-Input Multiple-Output (MIMO), or beamforming
      techniques. Yagi-Uda antennas combine high gain with low cost and reduced size,
      and might result in compact and efficient antennas to be used in Internet of
      Thins (IoT) sensors. The design of a compact multilayer Yagi for IoT sensors is
      presented, operating at 24 GHz, and a comparative analysis with a planar printed
      version is shown. The stacked prototype reveals an improvement of the antenna's
      main properties, achieving 10.9 dBi, 2 dBi more than the planar structure. In
      addition, the multilayer antenna shows larger bandwidth than the planar; 6.9 GHz
      compared with 4.42 GHz. The analysis conducted acknowledges the huge potential of
      these stacked structures for IoT applications, as an alternative to planar
      implementations.

PMID- 30200539
TI  - Genome-Based Classification and Therapy of Prostate Cancer.
AB  - In the past decade, multi-national and multi-center efforts were launched to
      sequence prostate cancer genomes, transcriptomes, and epigenomes with the aim of
      discovering the molecular underpinnings of tumorigenesis, cancer progression, and
      therapy resistance. Multiple biological markers and pathways have been discovered
      to be tumor drivers, and a molecular classification of prostate cancer is
      emerging. Here, we highlight crucial findings of these genome-sequencing projects
      in localized and advanced disease. We recapitulate the utility and limitations of
      current clinical practices to diagnosis, prognosis, and therapy, and we provide
      examples of insights generated by the molecular profiling of tumors. Novel
      treatment concepts based on these molecular alterations are currently being
      addressed in clinical trials and will lead to an enhanced implementation of
      precision medicine strategies.

PMID- 30200543
TI  - Tomato Juice Supplementation Influences the Gene Expression Related to Steatosis
      in Rats.
AB  - The objective of this work was to identify the effect of tomato juice on the
      expression of genes and levels of metabolites related to steatosis in rats. Male
      Sprague Dawley rats (8 weeks-old) were grouped (6 rats/group) in four
      experimental groups: NA (normal diet and water), NL (normal diet and tomato
      juice), HA (high-fat diet and water), and HL (high-fat diet and tomato juice).
      After an intervention period of 5 weeks, rats were sacrificed and biochemical
      parameters, biomarkers of oxidative stress, liver metabolites, and gene
      expression were determined. Although the H diet provoked dislipemia related to
      steatosis, no changes in isoprostanes or liver malondialdehyde (MDA) were
      observed. Changes in the gene expression of the HA group were produced by the
      high consumption of fat, whereas the consumption of tomato juice had different
      effects, depending on the diet. In the NL group, the genes involved in beta
      oxidation were upregulated, and in groups NL and HL upregulation of CD36 and
      downregulation of APOB and LPL were observed. In addition, in the HL group the
      accumulation of lycopene upregulated the genes FXR and HNF4A, which have been
      suggested as preventive factors in relation to steatosis. Regarding the
      metabolomics study, intake of tomato juice stimulated the biosynthesis of
      glutathione and amino acids of the transulfurization pathway, increasing the
      levels of metabolites related to the antioxidant response.

PMID- 30200546
TI  - Flood Detection in Gaofen-3 SAR Images via Fully Convolutional Networks.
AB  - Emergency flood monitoring and rescue need to first detect flood areas. This
      paper provides a fast and novel flood detection method and applies it to Gaofen-3
      SAR images. The fully convolutional network (FCN), a variant of VGG16, is
      utilized for flood mapping in this paper. Considering the requirement of flood
      detection, we fine-tune the model to get higher accuracy results with shorter
      training time and fewer training samples. Compared with state-of-the-art methods,
      our proposed algorithm not only gives robust and accurate detection results but
      also significantly reduces the detection time.

PMID- 30200545
TI  - Evaluation by the Ames Assay of the Mutagenicity of UV Filters Using Benzophenone
      and Benzophenone-1.
AB  - Ultraviolet absorbing chemicals (UV filters) are widely used in personal care
      products for protecting human skin and hair from damage by UV radiation. Although
      these substances are released into the environment during production and
      consumption processes, little is known about their genotoxicity effects. Our
      previous studies have shown that benzophenone-type UV filters exhibited acute
      toxicity on three species of aquatic organisms. Mutagenesis by benzophenone (BP)
      and benzophenone-1(BP-1) was tested in the present study by the Salmonella
      typhimurium/reverse mutation assay (Ames assay). All the positive reverse
      mutations occurred in the absence of the S9 liver extract system for both
      chemicals. From BP, positive mutation effects on the TA102 strain at doses of
      0.05 MUg/plate and 0.5 MUg/plate were detected. From BP-1, positive mutation
      effects on the TA97 strain at doses of 0.05 MUg/plate and 0.5 MUg/plate, and on
      the TA100 strain at a dose of 0.5 MUg/plate, were detected. A mixture of BP and
      BP-1 exhibited mutagenicity on the TA97 and TA100 strains. For the TA97 strain,
      the positive mutation results were detected at 10% and 50% of the mixture. For
      the TA100 strain, the results were detected when the mixture was at 5% and 10%.
      In the mixture at 5%, the concentrations of BP and BP-1 were 3.5 MUg/plate and 14
      MUg/plate, respectively. In the 10% mixture, the doses of BP and BP-1 were 7
      MUg/plate and 28 MUg/plate, respectively. In the 50% mixture, the doses of BP and
      BP-1 were 35 MUg/plate and 140 MUg/plate, respectively. The mixture test results
      suggested that there was antagonism in mutagenicity between BP and BP-1.

PMID- 30200547
TI  - Esterification of Aryl/Alkyl Acids Catalysed by N-bromosuccinimide under Mild
      Reaction Conditions.
AB  - N-halosuccinimides (NXSs) are well-known to be convenient, easily manipulable and
      low-priced halogenation reagents in organic synthesis. In the present work, N
      bromosuccinimide (NBS) has been promoted as the most efficient and selective
      catalyst among the NXSs in the reaction of direct esterification of aryl and
      alkyl carboxylic acids. Comprehensive esterification of substituted benzoic
      acids, mono-, di- and tri-carboxy alkyl derivatives has been performed under neat
      reaction conditions. The method is metal-free, air- and moisture-tolerant,
      allowing for a simple synthetic and isolation procedure as well as the large
      scale synthesis of aromatic and alkyl esters with yields up to 100%. Protocol for
      the recycling of the catalyst has been proposed.

PMID- 30200548
TI  - How Does Emotional Intelligence Make One Feel Better at Work? The Mediational
      Role of Work Engagement.
AB  - Although previous research has highlighted the association between emotional
      intelligence (EI) and job satisfaction, the underlying mechanisms remain
      relatively unexplored. To address this gap, this study examined employee
      engagement as a potential mediator of the association. A multi-occupational
      sample of 405 Spanish professionals completed the Wong Law Emotional Intelligence
      Scale, the Utrecht Work Engagement Scale and an Overall Job Satisfaction Scale as
      well as providing socio-demographic data. As expected, employees' EI was
      positively related to engagement dimensions (vigour, dedication and absorption)
      as well as overall job satisfaction. Bootstrap estimates from multiple mediation
      analysis confirmed that employees' perceived EI was indirectly associated with
      job satisfaction via vigour and dedication scores, even when controlling for the
      effects of socio-demographic variables. Similarly, the same pattern was found
      when multiple mediation was conducted for each EI dimension. Our study
      contributes to understanding of the processes involved in maintaining and
      enhancing positive attitudes at work, providing the first, encouraging evidence
      that work engagement play a role in the EI-job satisfaction link. Our results
      extend the EI literature by elucidating the pathways through which EI is linked
      to positive employee attitudes and suggests that intervention programs designed
      to bolster EI might prove effective at increasing job satisfaction.

PMID- 30200552
TI  - Electrochemical Engineering of Nanoporous Materials.

PMID- 30200549
TI  - Novel Synthetic Opioids: The Pathologist's Point of View.
AB  - BACKGROUND: New Psychoactive Substances (NPS) constitute a broad range of
      hundreds of natural and synthetic drugs, including synthetic opioids, synthetic
      cannabinoids, synthetic cathinones, and other NPS classes, which were not
      controlled from 1961 to 1971 by the United Nations drug control conventions.
      Among these, synthetic opioids represent a major threat to public health.
      METHODS: A literature search was carried out using public databases (such as
      PubMed, Google Scholar, and Scopus) to survey fentanyl-, fentanyl analogs-, and
      other synthetic opioid-related deaths. Keywords including "fentanyl", "fentanyl
      analogs", "death", "overdose", "intoxication", "synthetic opioids", "Novel
      Psychoactive Substances", "MT-45", "AH-7921", and "U-47700" were used for the
      inquiry. RESULTS: From our literature examination, we inferred the frequent
      implication of fentanyls and synthetic opioids in side effects, which primarily
      affected the central nervous system and the cardiovascular and pulmonary systems.
      The data showed a great variety of substances and lethal concentrations.
      Multidrug-related deaths appeared very common, in most reported cases.
      CONCLUSIONS: The investigation of the contribution of novel synthetic opioid
      intoxication to death should be based on a multidisciplinary approach aimed at
      framing each case and directing the investigation towards targeted toxicological
      analyses.

PMID- 30200553
TI  - A Novel Adsorbent Magnetic Graphene Oxide Modified with Chitosan for the
      Simultaneous Reduction of Mycotoxins.
AB  - A novel magnetic graphene oxide modified with chitosan (MGO-CTS) was synthesised
      as an adsorbent aimed to examine the simultaneous removal of mycotoxins. The
      composite was characterised by various procedures, namely Fourier-transform
      infrared spectroscopy (FTIR), X-ray diffraction (XRD) and a scanning electron
      microscope (SEM). The adsorption evaluation was considered via pH effects,
      initial mycotoxin concentration, adsorption time and temperature. Adsorption
      isotherm data and kinetics experiments were acquired at the optimum pH 5 fit
      Freundlich isotherm as well as pseudo-second-order kinetic models. The
      thermodynamic results indicated that the adsorption of the mycotoxins was
      spontaneous, endothermic and favourable.

PMID- 30200550
TI  - Catalytic Degradation of Diatrizoate by Persulfate Activation with Peanut Shell
      Biochar-Supported Nano Zero-Valent Iron in Aqueous Solution.
AB  - An emerging pollutant, diatrizoate (DTZ) has been frequently detected in aqueous
      solution. Unique reticular peanut shell biochar (BC)-supported nano zero-valent
      iron (nZVI) composite (nZVI/BC) was successfully synthesized and used as a
      catalyst for activating persulfate (PS) to promote the removal of DTZ. The
      structure and morphology of the nanocomposite materials were characterized by
      scanning electron microscopy, X-ray diffraction, Brunauer-Emmett-Teller
      measurements, and Fourier transform infrared spectroscopy. The degradation of DTZ
      (20 mg L-1) was achieved by activating PS with the nanocomposite material. The
      removal of DTZ reached nearly 100% using 25 mM PS and 0.45 g L-1 nZVI/2BC (mass
      ratio of nZVI and BC at 1:2) nanocomposite material at pH 3.0 and 25  degrees C.
      Influencing factors, such as dosages of nZVI/2BC and PS, temperature, and pH were
      also investigated. The mechanisms of PS activation with nZVI/2BC were discussed,
      including BC property, electron transfer, and the identification of free radicals
      in the reaction. The findings demonstrated that nZVI/BC-PS (peanut shell BC
      supported nZVI activating PS) is a promising material for the treatment of
      refractory organic pollutants.

PMID- 30200551
TI  - Liposomes Loaded with Cisplatin and Magnetic Nanoparticles: Physicochemical
      Characterization, Pharmacokinetics, and In-Vitro Efficacy.
AB  - With the aim improving drug delivery, liposomes have been employed as carriers
      for chemotherapeutics achieving promising results; their co-encapsulation with
      magnetic nanoparticles is evaluated in this work. The objective of this study was
      to examine the physicochemical characteristics, the pharmacokinetic behaviour,
      and the efficacy of pegylated liposomes loaded with cisplatin and magnetic
      nanoparticles (magnetite) (Cis-MLs). Cis-MLs were prepared by a modified reverse
      phase evaporation method. To characterize their physicochemical properties, an
      evaluation was made of particle size, zeta-potential, phospholipid and
      cholesterol concentration, phase transition temperature (Tm), the encapsulation
      efficiency of cisplatin and magnetite, and drug release profiles. Additionally,
      pharmacokinetic studies were conducted on normal Wistar rats, while apoptosis and
      the cytotoxic effect were assessed with HeLa cells. We present a method for
      simultaneously encapsulating cisplatin at the core and also embedding magnetite
      nanoparticles on the membrane of liposomes with a mean vesicular size of 104.4 +/
      11.5 nm and a zeta-potential of -40.5 +/- 0.8 mV, affording a stable formulation
      with a safe pharmacokinetic profile. These liposomes elicited a significant
      effect on cell viability and triggered apoptosis in HeLa cells.

PMID- 30200555
TI  - Colorimetric Determination of Hypochlorite Based on the Oxidative Leaching of
      Gold Nanorods.
AB  - Hypochlorite plays a critical role in killing microorganisms in the water.
      However, it can also cause cardiovascular diseases, neuron degeneration, and
      cancer to humans. Although traditional methods feature excellent sensitivity and
      reliability in detecting hypochlorite, the expensive instruments and strict
      determination conditions have limited their application in environmental analysis
      to some extent. Thus, it is necessary and urgent to propose a cheap, facile, and
      quick analytical assay for hypochlorite. This paper proposes a colorimetric assay
      for hypochlorite utilizing gold nanorods (AuNRs) as the nanoreactor and color
      reader. The AuNRs were acquired via a reported seed-mediated method. NaClO with
      strong oxidation property can cause the etching of gold from the longitudinal
      tips of AuNRs, which could shorten the aspect ratio of AuNRs, decrease the
      absorption in the UV-Vis spectrum and also induce the solution color changing
      from red to pale yellow. Thus, according to the solution color change and the
      absorbance of longitudinal surface plasmon resonance of AuNRs, we established the
      calibration curve of NaClO within 0.08 MUM to 125 MUM (?Abs = 0.0547 + 0.004
      CNaClO, R2 = 0.9631). Compared to traditional method, we obtained the conversion
      formula between the concentration of residual-chlorine in tap water and the
      concentration of hypochlorite detected by the proposed colorimetric assay, which
      is Cresidual-chlorine = 0.24 CNaClO. Finally, the real application of the
      colorimetric assay in tap water was successfully performed, and the accuracy of
      the colorimetric method can reach from -6.78% to +8.53%.

PMID- 30200556
TI  - Effects of Loading Frequency and Specimen Geometry on High Cycle and Very High
      Cycle Fatigue Life of a High Strength Titanium Alloy.
AB  - Titanium alloys have been widely used in the structural parts of deep-sea
      equipment and aviation industries. In this paper, the effects of loading
      frequency and specimen geometry on the high cycle and very high cycle fatigue
      life of the high strength titanium alloy Ti-6Al-2Sn-2Zr-3Mo-X is investigated by
      conventional fatigue test and ultrasonic frequency fatigue test. The results
      indicate that ultrasonic frequency could enhance the fatigue life of the
      highstrength titanium alloy compared with that under conventional frequency, and
      the frequency effect is related to the stress amplitude. This phenomenon is
      explained by the heat generation in specimens and heat dissipation, in
      combination with the high strain rate leading to the higher yield strength in the
      ultrasonic fatigue test. Moreover, it is indicated that the effect of specimen
      geometry on the fatigue life of the highstrength titanium alloy could be
      evaluated from the view of control volume.

PMID- 30200554
TI  - Anti-Inflammatory and Pro-Inflammatory Adipokine Profiles in Children on
      Vegetarian and Omnivorous Diets.
AB  - Adipose tissue is a highly active endocrine organ that secrets many pro
      inflammatory as well anti-inflammatory adipokines. The aim of the study was to
      assess serum adipokine profile in prepubertal vegetarian and omnivorous children.
      Sixty-two children on a vegetarian diet and fifty-five children on an omnivorous
      diet, aged 5 to 10 years, were studied. Dietary assessment was performed using a
      nutritional software program. Body composition was measured by dual-energy X-ray
      absorptiometry. Serum concentrations of adipokines: leptin, soluble leptin
      receptor (sOB-R), adiponectin (total and high molecular weight), resistin,
      visfatin, vaspin, and omentin were determined by immunoenzymatic assays. Both
      studied groups of children were comparable in terms of age, weight, height, body
      mass index, and body composition. Vegetarians had a lower (p = 0.017) leptin/sOB
      R ratio and lower serum concentrations of resistin (p = 0.051), compared with
      omnivores. Average levels of other adipokines did not differ between both groups
      of children. However, we observed significantly higher ratios of anti
      inflammatory to pro-inflammatory adipokines: adiponectin/leptin 0.70 (0.37-0.93)
      vs 0.39 (0.28-0.74), p = 0.005, and omentin/leptin 0.40 (0.23-0.83) vs. 0.33
      (0.15-0.48), p = 0.011 in vegetarians compared with omnivores. A well-planned
      vegetarian diet might beneficially affect the adipokine profile and inflammatory
      status expressed by the ratios of anti-inflammatory to pro-inflammatory
      adipokines in prepubertal children.

PMID- 30200558
TI  - A Comparative Study of Magnetic Properties of Large Diameter Co Nanowires and
      Nanotubes.
AB  - A comparative study of the magnetic properties of the arrays of Co nanowires and
      nanotubes with large external diameters (180 nm) has been carried out. The
      nanowires/nanotubes were grown by electrodeposition into the self-assembled pores
      of anodic alumina membranes. The experimental study of their magnetic behavior
      was focused on the angular dependence of hysteresis loops and their parameters.
      In both nanowire and nanotube arrays, from the analysis of experimental data,
      effective longitudinal magnetic anisotropy is concluded, which is stronger in the
      case of the nanotube array. In addition, the extremely small remanence observed
      for all loops indicates the important role played by magnetostatic interactions.
      Micromagnetic simulations were first performed considering intrinsic shape and
      magnetocrystalline anisotropy terms, together with an effective easy-plane
      anisotropy to account for those magnetostatic interactions. A qualitative
      agreement between experiments and simulations is found despite the complexity
      introduced by the intrinsic and extrinsic array properties (i.e., large
      diameters, grain structure, and array configuration). In addition, simulations
      were also carried out for individual nanowire/nanotube with a particular emphasis
      to understand their differences at the remanence, due to pure geometry
      contribution.

PMID- 30200557
TI  - Development of Dual Drug Loaded Nanosized Liposomal Formulation by A Reengineered
      Ethanolic Injection Method and Its Pre-Clinical Pharmacokinetic Studies.
AB  - Oleanolic acid (OA), which is a natural pentacyclic terpenoid, has been
      identified for hepato-protective, nephron-protective and cardio-tonic properties.
      In contrast, doxorubicin (DOX) is a famous anti-cancer drug but its efficacy is a
      question mark because of its known cardio-toxicity. We developed a combined
      nanoliposomal formulation of DOX with OA, as adjuvant, to overwhelm toxic effects
      of DOX without compromising anticancer activity. The entrapment efficiency and
      the particle size were brought in limit by the reengineered ethanolic injection
      method (REIM), without further extrusion. The developed formulations were stable
      over the study period of two months. A modified HPLC method was employed for the
      analysis of OA (drug retention time, Tr = 12 +/- 1 min). The recovery of OA
      against spiked plasma samples was more than 90%. MTT assay showed anti-apoptotic
      synergism against HepG2 cells at non-fixed ratio (combination index, CI < 1). A
      sustained in vivo drug release of experimental drugs was depicted over 24 h.
      Histopathological examination and laboratory findings indicated no visible sign
      of toxicity in the treated mice group against combined delivery. Hence, this
      combined nanoliposomal formulation was tagged as a safer therapy for the DOX
      based cancer treatments.

PMID- 30200559
TI  - Optimization of Ultrasonic-Assisted Extraction of Major Phenolic Compounds from
      Olive Leaves (Olea europaea L.) Using Response Surface Methodology.
AB  - The ultrasound-assisted extraction (UAE) of oleuropein (OLE), verbascoside (VER),
      and luteolin-4'-O-glucoside (L4OG), as the major phenolics from olive leaves, was
      optimized using response surface methodology (RSM). A Box-Behnken design (BBD)
      was used to monitor the effect of different modes of ultrasound operation (pulsed
      and continuous), liquid-solid (L-S) ratio, and sonication time on each phenolic
      yield. The yield of UAE and conventional solid extraction (CSE) was determined
      after performing ultrahigh-performance liquid chromatography with a diode-array
      detector (UHPLC-DAD) analysis on the extracts. The results suggested that, under
      optimal conditions, the concentrations of OLE, VER, and L4OG were 13.386, 0.363,
      and 0.527 mg/g of dry powdered olive leaves (DPOL), respectively. Verification of
      experiments was carried out under the modified optimal conditions and the
      relative errors between the predicted and experimental values were dependent on
      the examined phenolic compound (OLE 8.63%, VER 11.3%, and L4OG 22.48%). In
      comparison with CSE, UAE improved the yields of OLE, VER, and L4OG (32.6%, 41.8%,
      and 47.5%, respectively, after 1 min) at a temperature of 60  degrees C, an L-S
      ratio of 15 (v/w), and in the continuous mode of UAE. We demonstrated that the
      UAE technique is an efficient method for enhancing yields of OLE, VER, and L4OG
      in olive-leaf extracts, while the chosen model was adequate to optimize the
      extraction of major phenolic compounds from olive leaves.

PMID- 30200560
TI  - The Influence of Organizational Factors on Road Transport Safety.
AB  - Road transport safety is a major concern across Europe due to the human and socio
      economic costs associated with work-related traffic accidents. Traditional
      approaches have adopted regulatory and technical measures to prevent road
      accidents leaving aside the organizational factors that might contribute to road
      transport safety. However, contemporary sociotechnical systems theory
      acknowledges the need to take into account organizational factors. This study
      adopts a sociotechnical approach and it examines the relationship between a
      number of organizational factors (organizational learning and training) and road
      traffic accidents in the organizations under study. Our sample was composed of
      107 road transportation organizations from Spain. Binary logistic regression
      analyses were carried out to test our hypotheses. Organizational size and type of
      transport (goods or passengers) were included in the model as control variables.
      Results showed that in those organizations where organizational learning was
      supported, the occurrence of traffic accidents was less likely. Unexpectedly, the
      relationship between training and the occurrence of traffic accidents was not
      significant. Thus, findings partially supported the formulated hypothesis. Future
      research should shed light on the relationship between training and traffic
      accidents taking into account potential intervening variables.

PMID- 30200562
TI  - Glyphosate Determination by Coupling an Immuno-Magnetic Assay with
      Electrochemical Sensors.
AB  - Glyphosate (N-(phosphonomethyl)glycine) is the most frequently used broad
      spectrum herbicide worldwide. Its mechanism of action is based on the inhibition
      of an enzyme that is essential to plant growth. Its intensive use has caused
      global contamination to occur, which has not only affected the ecosystems, but
      even food and other objects of common use. Thus, there is a pronounced need for
      developing analytical methods for glyphosate determination in different matrices.
      Here, an electrochemical competitive immunoassay, based on the use of antibody
      modified magnetic particles, has been developed. Tetramethylbenzidine (TMB) has
      been used as an enzymatic substrate. The extent of the affinity reaction has been
      achieved by monitoring the current value, due to the reduction of the enzymatic
      product. A disposable screen-printed electrochemical cell has been used. The
      calibration curve has been recorded in the 0-10,000 ng/L concentration range,
      with a detection limit of 5 ng/L and quantification limit of 30 ng/L. The
      electrochemical immunoassay has also been applied to the analysis of spiked beer
      samples.

PMID- 30200561
TI  - Molecular and Physio-Biochemical Characterization of Cotton Species for Assessing
      Drought Stress Tolerance.
AB  - Drought stress significantly limits cotton growth and production due to the
      necessity of water at every stage of crop growth. Hence, it is essential to
      identify tolerant genetic resources and understand the mechanisms of drought
      tolerance in economically and socially important plants such as cotton. In this
      study, molecular and physio-biochemical investigations were conducted by
      analyzing different parameters by following standard protocols in three different
      cotton species, namely TM-1 (Gossypium hirsutum), Zhongmian-16 (Gossypium
      arboreum), and Pima4-S (Gossypium barbadense). Drought stress significantly
      decreased plant growth, chlorophyll content, net photosynthetic rate (Pn),
      stomatal conductance (Gs), maximum photochemical efficiency of PSII (Fv/Fm), and
      relative water content. TM-1 resulted in more tolerance than the other two
      species. The accumulation of proline, soluble proteins, soluble sugars, hydrogen
      peroxide (H2O2), and superoxide radicals (O2*-) increased significantly in TM-1.
      In addition, TM-1 maintained the integrity of the chloroplast structure under
      drought conditions. The relative expression level of drought-responsive genes
      including coding for transcription factors and other regulatory proteins or
      enzymes controlling genes (ERF, ERFB, DREB, WRKY6, ZFP1, FeSOD, CuZnSOD,
      MAPKKK17, P5CR, and PRP5) were higher in TM-1 under drought, conferring a more
      tolerant status than in Zhongmian-16 and Pima4-S. The findings of this research
      could be utilized for predicting a tolerant cotton genotype as well as evaluating
      prospective cotton species in the variety development program.

PMID- 30200563
TI  - Association between Air Quality and Sedentary Time in 3270 Chinese Adults:
      Application of a Novel Technology for Posture Determination.
AB  - This study investigated the association between ambient air quality and sedentary
      time in Chinese adults. The participants were 3270 Chinese users (2021 men and
      1249 women) of wrist-worn activity trackers. The data of participants' daily
      activities were collected from July 2015 to October 2015. A novel algorithm based
      on raw accelerometer data was employed to determine sedentary time. Personal
      data, including sex, age, weight and height, were self-reported by the
      participants. Data of air quality, ambient temperature and weather were collected
      from the data released by the China National Environmental Monitoring Centre and
      the China Central Meteorological Observatory and matched in accordance with the
      Global Positioning System and time information. Multilevel regression analyses
      were conducted to investigate the association between air quality and sedentary
      time and adjusted for gender, age, region, body mass index, weather, temperature,
      weekday/weekend and monitored wake time per day. Better air quality index levels
      and lower concentrations of fine particulate matter were significantly associated
      with approximately 20 and 45 min reduction in sedentary time, respectively. Poor
      air quality appears to be an independent factor associated with prolonged
      sedentary time in Chinese adults.

PMID- 30200564
TI  - Foods Contributing to Macronutrient Intake of Women Living in Puerto Rico Reflect
      Both Traditional Puerto Rican and Western-Type Diets.
AB  - Lack of variability in dietary intake within a population makes identification of
      relationships between diet and disease difficult. Studies in populations with
      greater interindividual variation can provide important insights. The Puerto
      Rican diet is in transition from a traditional to a more Western-type diet,
      resulting in greater interindividual variability. We identified foods
      contributing to absolute intake and variability in the intake of macronutrients
      among Puerto Rican women. One hundred women, aged 30-79, residents of San Juan,
      Puerto Rico, completed three, interviewer-administered, 24-h dietary recalls from
      which foods contributing to absolute intake and intake variability in intake of
      energy, fat, protein, carbohydrate and dietary fiber were determined. The overall
      prevalence of intake of foods was also calculated. Traditional Puerto Rican foods
      such as legumes, rice, and plantains were important contributors to the intake of
      calories and macronutrients as were foods more typical of Western diets including
      white bread and sweetened carbonated beverages. Identification of food sources of
      nutrients for this population with a diet in transition can contribute to the
      development of instruments to measure dietary intake and to understand the
      contribution of diet to the etiology of chronic disease among Puerto Rican women.

PMID- 30200566
TI  - A Device-Independent Efficient Actigraphy Signal-Encoding System for Applications
      in Monitoring Daily Human Activities and Health.
AB  - Actigraphs for personalized health and fitness monitoring is a trending niche
      market and fit aptly in the Internet of Medical Things (IoMT) paradigm.
      Conventionally, actigraphy is acquired and digitized using standard low pass
      filtering and quantization techniques. High sampling frequencies and quantization
      resolution of various actigraphs can lead to memory leakage and unwanted battery
      usage. Our systematic investigation on different types of actigraphy signals
      yields that lower levels of quantization are sufficient for acquiring and storing
      vital movement information while ensuring an increase in SNR, higher space
      savings, and in faster time. The objective of this study is to propose a low
      level signal encoding method which could improve data acquisition and storage in
      actigraphs, as well as enhance signal clarity for pattern classification. To
      further verify this study, we have used a machine learning approach which
      suggests that signal encoding also improves pattern recognition accuracy. Our
      experiments indicate that signal encoding at the source results in an increase in
      SNR (signal-to-noise ratio) by at least 50-90%, coupled with a bit rate reduction
      by 50-80%, and an overall space savings in the range of 68-92%, depending on the
      type of actigraph and application used in our study. Consistent improvements by
      lowering the quantization factor also indicates that a 3-bit encoding of
      actigraphy data retains most prominent movement information, and also results in
      an increase of the pattern recognition accuracy by at least 10%.

PMID- 30200567
TI  - Serum Parathyroid Hormone, 25-Hydroxyvitamin D, and Risk of Alzheimer's Disease:
      A Mendelian Randomization Study.
AB  - We conducted Mendelian randomization analyses to investigate the associations of
      serum parathyroid hormone (S-PTH) and serum 25-hydroxyvitamin D (S-25OHD)
      concentrations with Alzheimer's disease (AD). Five and seven single nucleotide
      polymorphisms associated with S-PTH and S-25OHD concentrations, respectively,
      were used as instrumental variables. Data for AD were acquired from the
      International Genomics of Alzheimer's Project (17,008 AD cases and 37,154
      controls). Genetically higher S-PTH concentrations were not associated with AD
      (odds ratio per standard deviation increase in S-PTH = 1.11; 95% CI 0.97-1.26; p
      = 0.12). In contrast, all seven 25OHD-increasing alleles were inversely
      associated with AD and two of the associations were statistically significant (p
      < 0.05). The odds ratio of AD per genetically-predicted one standard deviation
      increase in S-25OHD was 0.86 (95% CI 0.78-0.94; p = 0.002). This study provides
      evidence that vitamin D may play a role in AD but found no significant
      association between S-PTH and AD.

PMID- 30200565
TI  - Role of Vitamin A in the Immune System.
AB  - Vitamin A (VitA) is a micronutrient that is crucial for maintaining vision,
      promoting growth and development, and protecting epithelium and mucus integrity
      in the body. VitA is known as an anti-inflammation vitamin because of its
      critical role in enhancing immune function. VitA is involved in the development
      of the immune system and plays regulatory roles in cellular immune responses and
      humoral immune processes. VitA has demonstrated a therapeutic effect in the
      treatment of various infectious diseases. To better understand the relationship
      between nutrition and the immune system, the authors review recent literature
      about VitA in immunity research and briefly introduce the clinical application of
      VitA in the treatment of several infectious diseases.

PMID- 30200568
TI  - ZnO Nanowire Networks as Photoanode Model Systems for Photoelectrochemical
      Applications.
AB  - In this work, the fabrication of zinc oxide (ZnO) nanowire networks is presented.
      By combining ion-track technology, electrochemical deposition, and atomic layer
      deposition, hierarchical and self-supporting three-dimensional (3D) networks of
      pure ZnO- and TiO2-coated ZnO nanowires were synthesized. Analysis by means of
      high-resolution transmission electron microscopy revealed a highly crystalline
      structure of the electrodeposited ZnO wires and the anatase phase of the TiO2
      coating. In photoelectrochemical measurements, the ZnO and ZnO/TiO2 nanowire
      networks, used as anodes, generated higher photocurrents compared to those
      produced by their film counterparts. The ZnO/TiO2 nanowire network exhibited the
      highest photocurrents. However, the protection by the TiO2 coatings against
      chemical corrosion still needs improvement. The one-dimensionality of the
      nanowires and the large electrolyte-accessible area make these 3D networks
      promising photoelectrodes, due to the improved transport properties of
      photogenerated charge carriers and faster redox reactions at the surface.
      Moreover, they can find further applications in e.g., sensing, catalytical, and
      piezoelectric devices.

PMID- 30200569
TI  - Peiminine Protects against Lipopolysaccharide-Induced Mastitis by Inhibiting the
      AKT/NF-kappaB, ERK1/2 and p38 Signaling Pathways.
AB  - Peiminine, an alkaloid extracted from Fritillaria plants, has been reported to
      have potent anti-inflammatory properties. However, the anti-inflammatory effect
      of peiminine on a mouse lipopolysaccharide (LPS)-induced mastitis model remains
      to be elucidated. The purpose of this experiment was to investigate the effect of
      peiminine on LPS-induced mastitis in mice. LPS was injected through the canals of
      the mammary gland to generate the mouse LPS-induced mastitis model. Peiminine was
      administered intraperitoneally 1 h before and 12 h after the LPS injection. In
      vitro, mouse mammary epithelial cells (mMECs) were pretreated with different
      concentrations of peiminine for 1 h and were then stimulated with LPS. The
      mechanism of peiminine on mastitis was studied by hematoxylin-eosin staining
      (H&E) staining, western blotting, and enzyme-linked immunosorbent assay (ELISA).
      The results showed that peiminine significantly decreased the histopathological
      impairment of the mammary gland in vivo and reduced the production of pro
      inflammatory mediators in vivo and in vitro. Furthermore, peiminine inhibited the
      phosphorylation of the protein kinase B (AKT)/ nuclear factor-kappaB (NF-kappaB),
      extracellular regulated protein kinase (ERK1/2), and p38 signaling pathways both
      in vivo and in vitro. All the results suggested that peiminine exerted potent
      anti-inflammatory effects on LPS-induced mastitis in mice. Therefore, peiminine
      might be a potential therapeutic agent for mastitis.

PMID- 30200570
TI  - New Insights on the Pathogenesis of Takayasu Arteritis: Revisiting the Microbial
      Theory.
AB  - Takayasu arteritis (TAK) is a chronic vasculitis that mainly affects the aorta,
      its major branches, and the pulmonary arteries. Since the description of the
      first case by Mikito Takayasu in 1908, several aspects of this rare disease,
      including the epidemiology, diagnosis, and the appropriate clinical assessment,
      have been substantially defined. Nevertheless, while it is well-known that TAK is
      associated with a profound inflammatory process, possibly rooted to an autoimmune
      disorder, its precise etiology has remained largely unknown. Efforts to identify
      the antigen(s) that trigger autoimmunity in this disease have been unsuccessful,
      however, it is likely that viruses or bacteria, by a molecular mimicry mechanism,
      initiate or propagate the auto-immune process in this disease. In this article,
      we summarize recent advances in the understanding of TAK, with emphasis on new
      insights related to the pathogenesis of this entity that may contribute to the
      design of novel therapeutic approaches.

PMID- 30200571
TI  - Dietary Fructose Increases the Sensitivity of Proximal Tubules to Angiotensin II
      in Rats Fed High-Salt Diets.
AB  - Dietary fructose causes salt-sensitive hypertension. Proximal tubules (PTs)
      reabsorb 70% of the filtered NaCl. Angiotensin II (Ang II), atrial natriuretic
      peptide (ANP) and norepinephrine (NE) regulate this process. Although Ang II
      signaling blockade ameliorates fructose-induced salt-sensitive hypertension,
      basal PT Na+ reabsorption and its sensitivity to the aforementioned factors have
      not been studied in this model. We hypothesized consuming fructose with a high
      salt diet selectively enhances the sensitivity of PT transport to Ang II. We
      investigated the effects of Ang II, ANP and NE on PT Na reabsorption in rats fed
      a high-salt diet drinking tap water (HS) or 20% fructose (HS-FRU). Oxygen
      consumption (QO2) was used as a measure of all ATP-dependent transport processes.
      Na+/K+-ATPase and Na+/H+-exchange (NHE) activities were studied because they
      represent primary apical and basolateral transporters in this segment. The effect
      of 10-12 mol/L Ang II in QO2 by PTs from HS-FRU was larger than HS (p < 0.02; n =
      7). In PTs from HS-FRU 10-12 mol/L Ang II stimulated NHE activity by 2.6 +/- 0.7
      arbitrary fluorescence units/s (p < 0.01; n = 5) but not in those from HS. The
      stimulatory effect of Ang II on PT Na+/K+-ATPase activity was not affected by HS
      FRU. Responses of QO2 and NHE activity to ANP did not differ between groups. The
      response of QO2 to NE was unaltered by HS-FRU. We concluded that the sensitivity
      of PT Na+ reabsorption specifically to Ang II is enhanced by HS-FRU. This
      maintains high rates of transport even in the presence of low concentrations of
      the peptide, and likely contributes to the hypertension.

PMID- 30200573
TI  - A Phytochemical-Based Copolymer Derived from Coriolus versicolor
      Polysaccharopeptides for Gene Delivery.
AB  - Coriolus versicolor is an herb widely used for cancer treatment in traditional
      Chinese medicine. Its active ingredients, polysaccharopeptides (PSP), have been
      used for adjuvant therapies in cancer treatment. This study conjugates Coriolus
      versicolor PSP with poly(ethylenimine) (PEI) to generate a PSP-PEI copolymer for
      gene transfer. After PEI conjugation, both the pH buffering capacity and DNA
      compaction ability of PSP are significantly increased. Compared with that of PSP,
      the transfection efficiency of PSP-PEI is 10 to 20-fold higher in vitro. This is
      a proof-of-concept study reporting the direct use of bioactive phytochemicals
      from traditional Chinese medicine for gene vector development. The promising
      performance of PSP-PEI raises the possibility that bioactive herbal ingredients
      can be further developed as a multi-therapeutic gene carrier for tackling
      cancers.

PMID- 30200572
TI  - Dietary Interventions for the Prevention of Type 2 Diabetes in High-Risk Groups:
      Current State of Evidence and Future Research Needs.
AB  - A series of large-scale randomised controlled trials have demonstrated the
      effectiveness of lifestyle change in preventing type 2 diabetes in people with
      impaired glucose tolerance. Participants in these trials consumed a low-fat diet,
      lost a moderate amount of weight and/or increased their physical activity. Weight
      loss appears to be the primary driver of type 2 diabetes risk reduction, with
      individual dietary components playing a minor role. The effect of weight loss via
      other dietary approaches, such as low-carbohydrate diets, a Mediterranean dietary
      pattern, intermittent fasting or very-low-energy diets, on the incidence of type
      2 diabetes has not been tested. These diets-as described here-could be equally,
      if not more effective in preventing type 2 diabetes than the tested low-fat diet,
      and if so, would increase choice for patients. There is also a need to understand
      the effect of foods and diets on beta-cell function, as the available evidence
      suggests moderate weight loss, as achieved in the diabetes prevention trials,
      improves insulin sensitivity but not beta-cell function. Finally, prediabetes is
      an umbrella term for different prediabetic states, each with distinct underlying
      pathophysiology. The limited data available question whether moderate weight loss
      is effective at preventing type 2 diabetes in each of the prediabetes subtypes.

PMID- 30200575
TI  - Synthesizing and Reconstructing Missing Sensory Modalities in Behavioral Context
      Recognition.
AB  - Detection of human activities along with the associated context is of key
      importance for various application areas, including assisted living and well
      being. To predict a user's context in the daily-life situation a system needs to
      learn from multimodal data that are often imbalanced, and noisy with missing
      values. The model is likely to encounter missing sensors in real-life conditions
      as well (such as a user not wearing a smartwatch) and it fails to infer the
      context if any of the modalities used for training are missing. In this paper, we
      propose a method based on an adversarial autoencoder for handling missing sensory
      features and synthesizing realistic samples. We empirically demonstrate the
      capability of our method in comparison with classical approaches for filling in
      missing values on a large-scale activity recognition dataset collected in-the
      wild. We develop a fully-connected classification network by extending an encoder
      and systematically evaluate its multi-label classification performance when
      several modalities are missing. Furthermore, we show class-conditional artificial
      data generation and its visual and quantitative analysis on context
      classification task; representing a strong generative power of adversarial
      autoencoders.

PMID- 30200574
TI  - Neuropsychiatric Disorders: Influence of Gut Microbe to Brain Signalling.
AB  - The microbiome gut brain (MGB) axis consists of bidirectional routes of
      communication between the gut and the brain. It has emerged as a potential
      therapeutic target for multiple medical specialties including psychiatry.
      Significant numbers of preclinical trials have taken place with some
      transitioning to clinical studies in more recent years. Some positive results
      have been reported secondary to probiotic administration in both healthy
      populations and specific patient groups. This review aims to summarise the
      current understanding of the MGB axis and the preclinical and clinical findings
      relevant to psychiatry. Significant differences have been identified between the
      microbiome of patients with a diagnosis of depressive disorder and healthy
      controls. Similar findings have occurred in patients diagnosed with bipolar
      affective disorder and irritable bowel syndrome. A probiotic containing
      Lactobacillus acidophilus, Lactobacillus casei, and Bifidobacterium bifidum
      produced a clinically measurable symptom improvement in patients with depressive
      disorder. To date, some promising results have suggested that probiotics could
      play a role in the treatment of stress-related psychiatric disease. However, more
      well-controlled clinical trials are required to determine which clinical
      conditions are likely to benefit most significantly from this novel approach.

PMID- 30200577
TI  - Fatty Acid Lingual Application Activates Gustatory and Reward Brain Circuits in
      the Mouse.
AB  - The origin of spontaneous preference for dietary lipids in humans and rodents is
      debated, though recent compelling evidence has shown the existence of fat taste
      that might be considered a sixth taste quality. We investigated the implication
      of gustatory and reward brain circuits, triggered by linoleic acid (LA), a long
      chain fatty acid. The LA was applied onto the circumvallate papillae for 30 min
      in conscious C57BL/6J mice, and neuronal activation was assessed using c-Fos
      immunohistochemistry. By using real-time reverse transcription polymerase chain
      reaction (RT-qPCR), we also studied the expression of mRNA encoding brain-derived
      neurotrophic factor (BDNF), Zif-268, and Glut-1 in some brain areas of these
      animals. LA induced a significant increase in c-Fos expression in the nucleus of
      solitary tract (NST), parabrachial nucleus (PBN), and ventroposterior medialis
      parvocellularis (VPMPC) of the thalamus, which are the regions known to be
      activated by gustatory signals. LA also triggered c-Fos expression in the central
      amygdala and ventral tegmental area (VTA), involved in food reward, in
      conjunction with emotional traits. Interestingly, we noticed a high expression of
      BDNF, Zif-268, and Glut-1 mRNA in the arcuate nucleus (Arc) and hippocampus
      (Hipp), where neuronal activation leads to memory formation. Our study
      demonstrates that oral lipid taste perception might trigger the activation of
      canonical gustatory and reward pathways.

PMID- 30200576
TI  - Evaluation of the Surrounding Ring of Two Different Extra-Short Implant Designs
      in Crestal Bone Maintanence: A Histologic Study in Dogs.
AB  - The aim of this study was to compare the implant stability and bone resorption
      and formation of two different extra-short implant designs with different
      diameter rings placed in a dog's maxilla. Thirty-six extra-short, 5 mm diameter *
      4 mm length (Short DM(r), Bioner Sistemas Implantologicos, Barcelona, Spain),
      delayed implants were placed in each hemimaxilla of six dogs at the bone crest
      level. Eighteen implants of each design (wide and narrow ring) were installed.
      After 8 and 12 weeks of healing, histomorphometric analyses of the specimens were
      carried out to measure the crestal bone level values and the tissue thickness
      around the wide and narrow ring implant designs. In the microscopic analysis,
      less buccal bone resorption was observed in the narrow ring implants with a
      statistical significance (p < 0.001). For the peri-implant tissue thickness, the
      distance from the implant shoulder to the external portion of the epithelium was
      significantly higher for the implants installed with a wide ring with statistical
      significance (p < 0.001). Our findings suggest that the amount of peri-implant
      tissues (crestal bone loss) after remodeling over a period of 12 weeks was
      smaller in the narrow ring extra-short implant installed in the healed maxilla,
      compared with the wide ring extra-short implants.

PMID- 30200578
TI  - Application of Centrifugal Partition Chromatography for Bioactivity-Guided
      Purification of Antioxidant-Response-Element-Inducing Constituents from
      Atractylodis Rhizoma Alba.
AB  - Activity-guided separation of antioxidant response element (ARE)-inducing
      constituents from the rhizomes of Atractylodis Rhizoma Alba was performed by the
      combination of centrifugal partition chromatography (CPC) and an ARE luciferase
      reporter assay. From 3 g of the active n-hexane fraction, one polyacetylene,
      (6E,12E)-tetradeca-6,12-dien-8,10-diyne-1,3-diyl diacetate (47.3 mg), and two
      sesquiterpenes, atractylenolide I (40.9 mg), and selina-4(14),7(11)-dien-8-one
      (6.0 mg) were successfully isolated by CPC with n-hexane-ethyl acetate-methanol
      water (8:2:8:2, v/v). The chemical structures of the isolated compounds were
      determined by 1H- and 13C-NMR and ESI-MS. Among the isolated compounds, (6E,12E)
      tetradeca-6,12-diene-8,10-diyne-1,3-diol diacetate and selina-4(14),7(11)-dien-8
      one increased ARE activity 32.9-fold and 16.6-fold, respectively, without
      significant cytotoxicity, when 5 uM sulforaphane enhanced ARE activity 27.1-fold.
      However, atractylenolide I did not increase ARE activity at 100 uM, and showed
      cytotoxicity at concentrations over 10 uM.

PMID- 30200579
TI  - What Do Customers Demand from Drug Stores in Japan? Construct Validity and Factor
      Structure of a Cross-Sectional Survey.
AB  - Studies concerning patient demands are mainly conducted at hospitals and
      pharmacies, whereas few surveys have been conducted on drug stores. The demand
      for drug stores is estimated to be increasing with growing needs for self
      medication. Thus, conducting a customer survey at drug stores is thought to be
      valuable. The aim of the current study was to clarify the structure of customers'
      demands for drug stores. The survey was conducted on 190 customers of 19 drug
      stores in Japan. The questionnaire consisted of 24 items using a 9-point Likert
      scale. The IBM SPSS Statistics version 23 (IBM Japan, Tokyo, Japan) and Amos
      version 5 (IBM Japan, Tokyo, Japan) were utilized to perform factor analysis.
      Gender did not influence the response to each question. Factor analysis showed
      that the structure of customers' demands consisted of three factors: (1) an
      explanation about medicine, (2) staff's manners, and (3) location of drug stores.
      Because fit indices suggested a good fit, this three-factor solution was adopted
      as the final factor structure. This study demonstrated the structure of
      customers' demands for drug stores, with the potential for use in promotion of
      self-medication.

PMID- 30200581
TI  - Effect of Storage Conditions on Phenolic Profiles and Antioxidant Activity of
      Litchi Pericarp.
AB  - Changes of phenolic profiles and antioxidant activity of litchi pericarp during
      storage at 4  degrees C for seven days and at room temperature (RT) for 72 h were
      evaluated in this study. The contents of total phenolic and procyanidin decreased
      by 20.2% and 24.2% at 4  degrees C and by 37.8% and 47.8% at RT, respectively.
      Interestingly, the corresponding reductions of anthocyanins were 41.3% and 73%,
      respectively. Four phenolic compounds, including epicatechin, procyanidin A2,
      procyanidin B2, and quercetin-3-O-rutinoside-7-O-alpha-l-rhamnosidase were
      detected in litchi pericarp. Their contents after storage at 4  degrees C and at
      RT were decreased by 22.1-49.7% and 27.6-48.7%, respectively. The oxygen radical
      absorbance capacity (ORAC) and cellular antioxidant activity (CAA) of litchi
      pericarp decreased by 17.6% and 58.7% at 4  degrees C, and by 23.4% and 66.0% at
      RT, respectively. The results indicated that storage at 4  degrees C preserved
      more phenolics and retained higher antioxidant activity in litchi pericarp
      compared to storage at RT, suggesting that storage at 4  degrees C should be
      considered as a more effective method for slowing down the degradation of litchi
      pericarp phenolics.

PMID- 30200580
TI  - Evolution of Human Respiratory Syncytial Virus (RSV) over Multiple Seasons in New
      South Wales, Australia.
AB  - There is an ongoing global pandemic of human respiratory syncytial virus (RSV)
      infection that results in substantial annual morbidity and mortality. In
      Australia, RSV is a major cause of acute lower respiratory tract infections
      (ALRI). Nevertheless, little is known about the extent and origins of the genetic
      diversity of RSV in Australia, nor the factors that shape this diversity. We have
      conducted a genome-scale analysis of RSV infections in New South Wales (NSW). RSV
      genomes were successfully sequenced for 144 specimens collected between 2010
      2016. Of these, 64 belonged to the RSVA and 80 to the RSVB subtype. Phylogenetic
      analysis revealed a wide diversity of RSV lineages within NSW and that both
      subtypes evolved rapidly in a strongly clock-like manner, with mean rates of
      approximately 6-8 * 10-4 nucleotide substitutions per site per year. There was
      only weak evidence for geographic clustering of sequences, indicative of fluid
      patterns of transmission within the infected population and no evidence of any
      clustering by patient age such that viruses in the same lineages circulate
      through the entire host population. Importantly, we show that both subtypes
      circulated concurrently in NSW with multiple introductions into the Australian
      population in each year and only limited evidence for multi-year persistence.

PMID- 30200582
TI  - Effect of Whey Protein Supplementation on Physical Performance and Body
      Composition in Army Initial Entry Training Soldiers.
AB  - We investigated the effects of whey protein (WP) supplementation on body
      composition and physical performance in soldiers participating in Army Initial
      Entry Training (IET). Sixty-nine, male United States Army soldiers volunteered
      for supplementation with either twice daily whey protein (WP, 77 g/day protein,
      ~580 kcal/day; n = 34, age = 19 +/- 1 year, height = 173 +/- 6 cm, weight = 73.4
      +/- 12.7 kg) or energy-matched carbohydrate (CHO) drinks (CHO, 127 g/day
      carbohydrate, ~580 kcal/day; n = 35, age = 19 +/- 1 year, height = 173 +/- 5 cm,
      weight = 72.3 +/- 10.9 kg) for eight weeks during IET. Physical performance was
      evaluated using the Army Physical Fitness Test during weeks two and eight. Body
      composition was assessed using 7-site skinfold assessment during weeks one and
      nine. Post-testing push-up performance averaged 7 repetitions higher in the WP
      compared to the CHO group (F = 10.1, p < 0.001) when controlling for baseline.
      There was a significant decrease in fat mass at post-training (F = 4.63, p =
      0.04), but no significant change in run performance (F = 3.50, p = 0.065) or fat
      free mass (F = 0.70, p = 0.41). Effect sizes for fat-free mass gains were large
      for both the WP (Cohen's d = 0.44) and CHO (Cohen's d = 0.42) groups. WP had a
      large effect on fat mass (FM) loss (Cohen's d = -0.67), while CHO had a medium
      effect (Cohen's d = -0.40). Twice daily supplementation with WP improved push-up
      performance and potentiated reductions in fat mass during IET training in
      comparison to CHO supplementation.

PMID- 30200583
TI  - Experimental Investigation on 3D Graphene-CNT Hybrid Foams with Different
      Interactions.
AB  - Due to the exceptional properties of graphene, numerous possibilities for real
      applications in various fields have been provided. However, it is a challenge to
      fabricate bulk graphene materials with properties arising from the nature of
      individual graphene sheets, and which assemble into monolithic three-dimensional
      structures. If 3D structured graphene foam were made instead of 2D structured
      graphene, it is expected that it would be a facile fabrication, with relatively
      low cost with the possibility of scale-up, and would maintain the intrinsic
      properties of graphene. To solve the weaknesses of 2D structured graphene, this
      study aimed to fabricate a 3D graphene-carbon nanotubes (CNT) hybrid foam. In
      this study, CNT was used to reinforce the graphene foams. In addition, two
      different surfactants, known as sodium dodecylbenzene sulphonate (SDBS) and
      cetyltrimethylammonium bromide (CTAB), were applied to help CNT dispersion. The
      pi-pi interaction was induced by SDBS/CNT, while ionic interaction was derived
      from CTAB/CNT. To confirm the charge effect with different surfactants, SEM, Zeta
      potential, FT-IR, Raman spectroscopy, and compression tests were performed. When
      using a cationic surfactant, CTAB, compressive modulus, and strength increased
      due to the formation of relatively strong ionic bonding.

PMID- 30200584
TI  - Molecular Recognition via Hydrogen Bonding in Supramolecular Complexes: A Fourier
      Transform Infrared Spectroscopy Study.
AB  - We assess the assembly of supramolecular complexes by hydrogen bonding between
      azocompounds and a diacylaminopyridine monomer by temperature-dependent Fourier
      transform infrared spectroscopy (FT-IR) and density functional theory (DFT)
      calculations. The electronic delocalisation in the supramolecular rings formed by
      multiple hydrogen bonds stabilises the complexes, which coexist with dimeric
      species in temperature-dependent equilibria. We show how the application of
      readily available molecular modelling and spectroscopic techniques can predict
      the stability of new supramolecular entities coexisting in equilibria, ultimately
      assessing the success of molecular recognition.

PMID- 30200585
TI  - (+)-Aeroplysinin-1 Modulates the Redox Balance of Endothelial Cells.
AB  - The bioactive natural compound from marine origin, (+)-aeroplysinin-1, has been
      shown to exhibit potent anti-inflammatory and anti-angiogenic effects. The aim of
      the present study was to identify new targets for (+)-aeroplysinin-1 in
      endothelial cells. The sequential use of 2D-electrophoresis and MALDI-TOF-TOF/MS
      allowed us to identify several differentially expressed proteins. Four of these
      proteins were involved in redox processes and were validated by Western blot. The
      effects of (+)-aeroplysinin-1 were further studied by testing the effects of the
      treatment with this compound on the activity of several anti- and pro-oxidant
      enzymes, as well as on transcription factors involved in redox homeostasis.
      Finally, changes in the levels of total reactive oxygen species and mitochondrial
      membrane potential induced by endothelial cell treatments with (+)-aeroplysinin-1
      were also determined. Taken altogether, these findings show that (+)-aeroplysinin
      1 has multiple targets involved in endothelial cell redox regulation.

PMID- 30200586
TI  - Simple and Label-Free Fluorescent Detection of Melamine Based on Melamine-Thymine
      Recognition.
AB  - In the past few years, melamine has been illegally added into dairy products to
      increase the apparent crude protein levels. If humans or animals drink the milk
      adulteration of melamine, it can form insoluble melamine-cyanurate crystals in
      their kidneys which causes kidney damage or even death. In the present work, we
      constructed a simple and label-free fluorescent method for melamine detection
      based on melamine-thymine recognition. SYBR Green I was utilized as a reporter
      for this method as it did not require any modification or expensive equipment. In
      the absence of melamine, polythymine DNA was digested by Exo I, which caused a
      decrease in the fluorescence signal. In the presence of melamine, the polythymine
      DNA was able to fold into a double chain structure, however this was done with
      the help of T-melamine-T mismatches to prevent degradation. Then, the SYBR Green
      I combined with the double-stranded DNA to result in an intense fluorescence
      signal. The limit of detection in this method was 1.58 MUM, which satisfied the
      FDA standards. This method also had a good linear relationship within the range
      of 10-200 MUM. In addition, this new method has a good selectivity to distinguish
      melamine from the component of milk. As a result, we developed a simple and
      highly selectivity method for melamine detection.

PMID- 30200587
TI  - Pharmacokinetics and Anti-Gastric Ulceration Activity of Oral Administration of
      Aceclofenac and Esomeprazole in Rats.
AB  - This study examined the effects of esomeprazole on aceclofenac pharmacokinetics
      and gastrointestinal complications in rats. Aceclofenac alone, or in combination
      with esomeprazole, was orally administered to male Sprague-Dawley rats. Plasma
      concentrations of aceclofenac, its major metabolite diclofenac, and esomeprazole
      were simultaneously determined by a novel liquid chromatography-tandem mass
      spectrometry method. Gastrointestinal damage was determined by measuring ulcer
      area and ulcer lesion index of the stomach. Oral administration of aceclofenac
      induced significant gastric ulceration, which was inhibited by esomeprazole
      administration. Following concurrent administration of aceclofenac and
      esomeprazole, overall pharmacokinetic profiles of aceclofenac and metabolic
      conversion to diclofenac were unaffected by esomeprazole. Aceclofenac metabolism
      and pharmacokinetics were not subject to significant food effects, whereas
      bioavailability of esomeprazole decreased in fed compared to fasting conditions.
      In contrast, the pharmacokinetics of aceclofenac and esomeprazole were
      significantly altered by different dosing vehicles. These results suggest that co
      administration of esomeprazole with aceclofenac may reduce aceclofenac-induced
      gastrointestinal complications without significant pharmacokinetic interactions.
      The optimal combination and clinical significance of the benefits of the
      combination of aceclofenac and esomeprazole need to be further evaluated.

PMID- 30200588
TI  - Synthesis and Characterization of Bis[1]benzothieno[3,2-b:2',3'-d]pyrroles:
      Quantitative Effects of Benzannulation on Dithieno[3,2-b:2',3'-d]pyrroles.
AB  - The synthesis of four N-functionalized bis[1]benzothieno[3,2-b:2',3'-d]pyrroles
      (BBTPs) is reported in order to provide a more detailed characterization of these
      fused-ring units, as well as increase the scope of known BBTP units available for
      application to conjugated materials. The optical, electronic, and structural
      properties of the resulting BBTP units have been compared to the parent N-alkyl-
      and N-aryl-dithieno[3,2-b:2',3'-d]pyrroles (DTPs), as well as their corresponding
      2,6-diphenyl derivatives, in order to fully quantify the relative electronic
      effects resulting from benzannulation of the parent DTP building block. Such
      comparative analysis reveals that benzannulation results in a red-shifted
      absorbance, but to a lesser extent than simple phenyl-capping of the DTP. More
      surprising is that benzannulation results in stabilization of the BBTP HOMO,
      compared to the destabilization normally observed with extending the conjugation
      length of the backbone.

PMID- 30200589
TI  - Applicability of Yeast Fermentation to Reduce Fructans and Other FODMAPs.
AB  - A diet low in fermentable oligosaccharides, disaccharides, monosaccharides and,
      polyols (FODMAPs) is recommended for people affected by irritable bowel syndrome
      (IBS) and non-coeliac wheat sensitivity (NCWS) in order to reduce symptoms.
      Therefore, the aim of this study was to evaluate the impact of 13 sourdough
      related yeasts on FODMAP degradation, especially fructans. First, a model system
      containing a typical wheat carbohydrate profile was applied to evaluate the
      growth rate of each yeast strain. Additionally, changes in the sugar composition,
      for up to four days, were monitored by high-pressure anion-exchange
      chromatography (HPAEC). A more realistic approach with a wheat flour suspension
      was used to characterize CO2 production according to the Einhorn method. The
      reduction of the total fructans was analyzed using an enzymatic method.
      Furthermore, a fingerprint of the present fructans with different degrees of
      polymerization was analyzed by HPAEC. The results revealed strong differences in
      the examined yeast strains' ability to degrade fructans, in both the model system
      and wheat flour. Overall, Saccharomycescerevisiae isolated from Austrian
      traditional sourdough showed the highest degree of degradation of the total
      fructan content and the highest gas building capacity, followed by
      Torulasporadelbrueckii. Hence, this study provides novel knowledge about the
      FODMAP conversion of yeast strains.

PMID- 30200590
TI  - Clinical Safety of Combined Targeted and Viscum album L. Therapy in Oncological
      Patients.
AB  - Background: Despite improvement of tumor response rates, targeted therapy may
      induce toxicities in cancer patients. Recent studies indicate amelioration of
      adverse events (AEs) by add-on mistletoe (Viscum album L., VA) in standard
      oncological treatment. The primary objective of this multicenter observational
      study was to determine the safety profile of targeted and add-on VA therapy
      compared to targeted therapy alone. Methods: Demographic and medical data were
      retrieved from the Network Oncology registry. Allocation to either control
      (targeted therapy) or combinational group (targeted/add-on VA) was performed.
      Safety-associated variables were evaluated by adjusted multivariable analyses.
      Results: The median age of the study population (n = 310) at first diagnosis was
      59 years; 67.4% were female. In total, 126 patients (40.6%) were in the control
      and 184 patients (59.4%) in the combination group. Significant differences were
      observed between both groups with respect to overall AE frequency (chi2 = 4.1, p
      = 0.04) and to discontinuation of standard oncological treatment (chi2 = 4.8, p =
      0.03) with lower rates in the combinational group (20.1%, 35% respectively)
      compared to control (30.2%, 60.5%, respectively). Addition of VA to targeted
      therapy significantly reduced the probability of oncological treatment
      discontinuation by 70% (Odds ratio (OR) 0.30, p = 0.02). Conclusions: Our results
      indicate a highly significant reduction of AE-induced treatment discontinuation
      in all-stage cancer patients when treated with VA in addition to targeted
      therapy.

PMID- 30200591
TI  - Noise Analysis of Monolayer Graphene Nanopores.
AB  - Graphene-based nanopore devices have shown tantalizing potential in single
      molecule detection for their monoatomic membrane thickness which is roughly equal
      to the gap between nucleobases. However, high noise level hampers applications of
      graphene nanopore sensors, especially at low frequencies. In this article, we
      report on a study of the contribution of suspended graphene area to noise level
      in full frequency band. Monolayer graphene films are transferred onto SiNx
      substrates preset with holes in varied diameters and formed self-supported films.
      After that, the films are perforated with smaller, nanoscale holes. Experimental
      studies indicate a dependency of low-frequency 1/f noise on the underlying SiNx
      geometry. The contribution of the suspended graphene area to capacitance which
      affects the noise level in the high frequency range reveals that the graphene
      free-standing film area influences noise level over a wide frequency region. In
      addition, the low-frequency noise demonstrates a weak dependency on salt
      concentration, in deviation from Hooge's relation. These findings and attendant
      analysis provide a systematic understanding of the noise characteristics and can
      serve as a guide to designing free-standing monolayer graphene nanopore devices.

PMID- 30200593
TI  - Correction: Kinchin, I.; Doran, C.M. The Cost of Youth Suicide in Australia. Int.
      J. Environ. Res. Public Health 2018, 15, 672.
AB  - The authors wish to add the following corrections to their paper published in the
      International Journal of Environmental Research and Public Health[...].

PMID- 30200594
TI  - Using the Equivalent Fiber Approach in Two-Scale Modeling of the Elastic Behavior
      of Carbon Nanotube/Epoxy Nanocomposite.
AB  - In this study, the mechanical behavior of epoxy/carbon nanotubes (CNTs)
      nanocomposite is predicated by a two-scale modeling approach. At the nanoscale, a
      CNT, the interface between the CNT and the matrix and a layer of the matrix
      around the CNT are modeled and the elastic behavior of the equivalent fiber (EF)
      has been identified. The CNT/epoxy interface behavior is modeled by the Park
      Paulino-Roesler (PPR) potential. At the microscale, the EFs are embedded in the
      matrix with the extracted elastic properties from the nanoscale model. The random
      pattern has been used for the dispersing of EFs in the representative volume
      element (RVE). The effect of CNTs agglomeration in the epoxy matrix has also been
      investigated at the micro level. The Young's modulus of the nanocomposite was
      extracted from simulation of the RVE. CNT/epoxy nanocomposites at four different
      volume fractions were manufactured and the modeling results were validated by
      tensile tests. The results of the numerical models are in good agreement with the
      experiments and micromechanics theory, and by considering agglomeration of CNT in
      the model, the modeling results match with the experiments.

PMID- 30200592
TI  - Effects of Vegetable Proteins on Hypercholesterolemia and Gut Microbiota
      Modulation.
AB  - Risk assessment tools, i.e., validated risk prediction algorithms, to estimate
      the patient's 10-year risk of developing cardiovascular disease (CVD) should be
      used to identify high-risk people for primary prevention. Current evidence
      confirms that appropriate monitoring and control of risk factors either reduces
      the likelihood of CVD or slows down its progression. It is thus crucial that all
      health professionals make appropriate use of all the available intervention
      strategies to control risk factors: from dietary improvement and adequate
      physical activity to the use of functional foods, food supplements, and drugs.
      The gut microbiota, which encompasses 1 * 1014 resident microorganisms, has been
      recently recognized as a contributing factor in the development of human disease.
      This review examines the effect of both some vegetable food components belong to
      the "protein food group" and the underexploited protein-rich hempseed on
      cholesterolemia and gut microbiota composition.

PMID- 30200596
TI  - Research Status and Prospect on Vanadium-Based Catalysts for NH3-SCR Denitration.
AB  - Selective catalytic reduction of NOx with NH3 is one of the most widely used
      technologies in denitration. Vanadium-based catalysts have been extensively
      studied for the deNOx process. V2O5/WO3(MoO3)TiO2 as a commercial catalyst has
      excellent catalytic activity in the medium temperature range. However, it has
      usually faced several problems in practical industrial applications, including
      narrow windows of operation temperatures, and the deactivation of catalysts. The
      modification of vanadium-based catalysts will be the focus in future research. In
      this paper, the chemical composition of vanadium-based catalysts, catalytic
      mechanism, the broadening of the temperature range, and the improvement of
      erosion resistance are reviewed. Furthermore, the effects of four major systems
      of copper, iron, cerium and manganese on the modification of vanadium-based
      catalysts are introduced and analyzed. It is worth noting that the addition of
      modified elements as promoters has greatly improved the catalytic performance.
      They can enhance the surface acidity, which leads to the increasing adsorption
      capacity of NH3. Surface defects and oxygen vacancies have also been increased,
      resulting in more active sites. Finally, the future development of vanadium-based
      catalysts for denitration is prospected. It is indicated that the main purpose
      for the research of vanadium-based modification will help to obtain safe,
      environmentally friendly, efficient, and economical catalysts.

PMID- 30200595
TI  - A Multi-Sensor Matched Filter Approach to Robust Segmentation of Assisted Gait.
AB  - Individuals with mobility impairments related to age, injury, or disease, often
      require the help of an assistive device (AD) such as a cane to ambulate, increase
      safety, and improve overall stability. Instrumenting these devices has been
      proposed as a non-invasive way to proactively monitor an individual's reliance on
      the AD while also obtaining information about behaviors and changes in gait. A
      critical first step in the analysis of these data, however, is the accurate
      processing and segmentation of the sensor data to extract relevant gait
      information. In this paper, we present a highly accurate multi-sensor-based gait
      segmentation algorithm that is robust to a variety of walking conditions using an
      AD. A matched filtering approach based on loading information is used in
      conjunction with an angular rate reversal and peak detection technique, to
      identify important gait events. The algorithm is tested over a variety of
      terrains using a hybrid sensorized cane, capable of measuring loading, mobility,
      and stability information. The reliability and accuracy of the proposed multi
      sensor matched filter (MSMF) algorithm is compared with variations of the
      commonly employed gyroscope peak detection (GPD) algorithm. Results of an
      experiment with a group of 30 healthy participants walking over various terrains
      demonstrated the ability of the proposed segmentation algorithm to reliably and
      accurately segment gait events.

PMID- 30200597
TI  - A Hybrid Forecasting Approach to Air Quality Time Series Based on Endpoint
      Condition and Combined Forecasting Model.
AB  - Air pollution forecasting plays a vital role in environment pollution warning and
      control. Air pollution forecasting studies can also recommend pollutant emission
      control strategies to mitigate the number of poor air quality days. Although
      various literature works have focused on the decomposition-ensemble forecasting
      model, studies concerning the endpoint effect of ensemble empirical mode
      decomposition (EEMD) and the forecasting model of sub-series selection are still
      limited. In this study, a hybrid forecasting approach (EEMD-MM-CFM) is proposed
      based on integrated EEMD with the endpoint condition mirror method and combined
      forecasting model for sub-series. The main steps of the proposed model are as
      follows: Firstly, EEMD, which sifts the sub-series intrinsic mode functions
      (IMFs) and a residue, is proposed based on the endpoint condition method. Then,
      based on the different individual forecasting methods, an optimal combined
      forecasting model is developed to forecast the IMFs and residue. Finally, the
      outputs are obtained by summing the forecasts. For illustration and comparison,
      air quality index (AQI) data from Hefei in China are used as the sample, and the
      empirical results indicate that the proposed approach is superior to benchmark
      models in terms of some forecasting assessment measures. The proposed hybrid
      approach can be utilized for air quality index forecasting.

PMID- 30200598
TI  - Bradykinin B2 Receptor Contributes to Inflammatory Responses in Human Endothelial
      Cells by the Transactivation of the Fibroblast Growth Factor Receptor FGFR-1.
AB  - Elevated levels of bradykinin (BK) and fibroblast growth factor-2 (FGF-2) have
      been implicated in the pathogenesis of inflammatory and angiogenic disorders. In
      angiogenesis, both stimuli induce a pro-inflammatory signature in endothelial
      cells, activating an autocrine/paracrine amplification loop that sustains the
      neovascularization process. Here we investigated the contribution of the FGF-2
      pathway in the BK-mediated human endothelial cell permeability and migration, and
      the role of the B2 receptor (B2R) of BK in this cross-talk. BK (1 uM) upregulated
      the FGF-2 expression and promoted the FGF-2 signaling, both in human umbilical
      vein endothelial cells (HUVEC) and in retinal capillary endothelial cells (HREC)
      by the activation of Fibroblast growth factor receptor-1 (FGFR-1) and its
      downstream signaling (fibroblast growth factor receptor substrate: FRSalpha,
      extracellular signal-regulated kinases1/2: ERK1/2, and signal transducer and
      activator of transcription 3: STAT3 phosphorylation). FGFR-1 phosphorylation
      triggered by BK was c-Src mediated and independent from FGF-2 upregulation.
      Either HUVEC and HREC exposed to BK showed increased permeability, disassembly of
      adherens and tight-junction, and increased cell migration. B2R blockade by the
      selective antagonist, fasitibant, significantly inhibited FGF-2/FGFR-1 signaling,
      and in turn, BK-mediated endothelial cell permeability and migration. Similarly,
      the FGFR-1 inhibitor, SU5402, and the knock-down of the receptor prevented the
      BK/B2R inflammatory response in endothelial cells. In conclusion, this work
      demonstrates the existence of a BK/B2R/FGFR-1/FGF-2 axis in endothelial cells
      that might be implicated in propagation of angiogenic/inflammatory responses. A
      B2R blockade, by abolishing the initial BK stimulus, strongly attenuated FGFR-1
      driven cell permeability and migration.

PMID- 30200599
TI  - Chemical Identification of Isoflavonoids from a Termite-Associated Streptomyces
      sp. RB1 and Their Neuroprotective Effects in Murine Hippocampal HT22 Cell Line.
AB  - Insect-associated bacteria have been recognized as a very promising natural
      resource for discovering bioactive secondary metabolites with diverse
      pharmacological effects. One new isoflavonoid glycoside, termisoflavone D (1),
      together with seven known isoflavonoids (2-8), were identified from MeOH extracts
      of the fungus-growing termite-associated Streptomyces sp. RB1. The chemical
      structure of the new compound 1 was elucidated using comprehensive spectroscopic
      methods including 1D and 2D NMR, along with LC/MS analysis. The existence of two
      rhamnose moieties in 1 was determined with comparative NMR analysis, and the
      absolute configuration was elucidated using chemical reactions. The
      neuroprotective activities of compounds 1-8 were thoroughly investigated using
      the murine hippocampal HT22 cell line. Compound 5 prevented glutamate-induced
      HT22 cell death by blocking intracellular reactive oxygen species (ROS)
      accumulation. The present study provides the first experimental evidence for the
      potential use of isoflavonoids from termite-associated bacteria as lead compounds
      that can prevent neuronal damage induced by glutamate.

PMID- 30200600
TI  - Novel Phenolic Constituents of Pulmonaria officinalis L. LC-MS/MS Comparison of
      Spring and Autumn Metabolite Profiles.
AB  - Lungwort (Pulmonaria officinalis L., Boraginaceae) is considered to possess
      therapeutic properties and it has been traditionally used as a remedy against
      various lung disorders in many countries. Nevertheless, very few data concerning
      its phytochemical composition are available. This research aims to provide a
      detailed description of specialized metabolites from the aerial parts of
      lungwort. Nine previously undescribed and 36 known phenolic compounds were
      detected in the 50% methanolic extract. Following multistep preparative
      procedures, structures of newly discovered compounds were determined using one-
      and two-dimensional techniques of NMR spectroscopy. Among the identified
      compounds were caffeic acid esters with aliphatic hydroxycarboxylic acids,
      conjugates of dicaffeic acid with rosmarinic acid, and previously unknown isomers
      of isosalvianolic acid A and yunnaneic acid E, as well as other lignans.
      Concentrations of all identified phenolic derivatives in the investigated herbal
      material were estimated using a method based on liquid chromatography with high
      resolution mass spectrometry detection. Seasonal changes in the concentration of
      metabolites were also investigated using targeted and untargeted metabolomics
      techniques.

PMID- 30200601
TI  - Characteristics of Cyp11a during Gonad Differentiation of the Olive Flounder
      Paralichthys olivaceus.
AB  - The P450 side-chain cleavage enzyme, P450scc (Cyp11a) catalyzes the first
      enzymatic step for the synthesis of all steroid hormones in fish. To study its
      roles in gonads of the olive flounder Paralichthys olivaceus, an important
      maricultured fish species, we isolated the cyp11a genomic DNA sequence of 1396
      bp, which consists of 5 exons and 4 introns. Semi-quantitative reverse
      transcription polymerase chain reaction (RT-PCR) results indicated that the
      flounder cyp11a was exclusively expressed in gonad and head kidney tissues. Its
      expression level in the testis was higher than that in the ovary. According to
      the in situ hybridization patterns, cyp11a was mainly expressed in the Leydig
      cells of the testis, and the thecal cells of the ovary. Immunofluorescence
      analysis showed that Cyp11a was located in the cytoplasm of the cultured flounder
      testis cells. Further quantitative real-time PCR results presented the cyp11a
      differential expression patterns during gonad differentiation. Among different
      sampling points of the 17beta-estradiol (E2, 5 ppm) treatment group, cyp11a
      expression levels were relatively high in the differentiating ovary (30 and 40 mm
      total length, TL), and then significantly decreased in the differentiated ovary
      (80, 100 and 120 mm TL, p < 0.05). The pregnenolone level also dropped in the
      differentiated ovary. In the high temperature treatment group (HT group, 28 +/-
      0.5  degrees C), the cyp11a expression level fluctuated remarkably in the
      differentiating testis (60 mm TL), and then decreased in the differentiated
      testis (80, 100 mm TL, p < 0.05). In the testosterone (T, 5 ppm) treatment group,
      the cyp11a was expressed highly in undifferentiated gonads and the
      differentiating testis, and then dropped in the differentiated testis. Moreover,
      the levels of cholesterol and pregnenolone of the differentiating testis in the
      HT and T groups increased. The expression level of cyp11a was significantly down
      regulated after the cultured flounder testis cells were treated with 75 and 150
      MUM cyclic adenosine monophosphate (cAMP), respectively (p < 0.05), and
      significantly up-regulated after treatment with 300 MUM cAMP (p < 0.05). Both
      nuclear receptors NR5a2 and NR0b1 could significantly up-regulate the cyp11a gene
      expression in a dosage dependent way in the testis cells detected by cell
      transfection analysis (p < 0.05). The above data provides evidence that cyp11a
      would be involved in the flounder gonad differentiation and development.

PMID- 30200602
TI  - Elevated Indoor Volatile Organic Compound Exposure in the Niger Delta Region of
      Nigeria.
AB  - The implications of environmental contamination on human health in the Niger
      Delta region of Nigeria remain a topic of growing international public health
      interest. To better understand ongoing air pollution and initiate remediation
      efforts, the United Nations Environmental Programme (UNEP) report recommended the
      monitoring of volatile organic compounds (VOCs) across different media (water,
      soil, and air) in Ogoniland, an at-risk population in the Niger Delta region of
      Nigeria. In this pilot study, we measured indoor VOC concentrations in the indoor
      air of 20 households in Ogale, an Ogoniland community whose groundwater system is
      contaminated with benzene at levels 900 times the World Health Organization
      guidelines and evaluated self-reported health conditions and predicted cancer
      risks and hazards from inhalation exposure to VOCs. We detected higher
      concentrations of benzene (mean = 25.7 MUg/m3, SD = 23.2 MUg/m3) and naphthalene
      (mean = 7.6 MUg/m3, SD = 13.8 MUg/m3) than has been reported in other regions.
      Although study participants reported health symptoms consistent with VOC
      exposure, we were underpowered to detect a significant association between select
      indoor VOCs and these self-reported health symptoms using univariate logistic
      regression models. These findings suggest that that the health symptoms reported
      by participants may be poor proxies for the underlying disease processes
      associated with adverse health outcomes due to VOC exposure in this community and
      that the burden of adverse health effects due to VOC exposure may stem from the
      contaminated groundwater system. We estimated a non-cancer hazard quotient of 3
      from exposure to naphthalene and lifetime excess cancer risks from exposure to
      naphthalene, benzene, p-dichlorobenzene, carbon tetrachloride, and ethylbenzene
      of 3 * 10-4, 2 * 10-4, 6 * 10-5, 6 * 10-6, and 1 * 10-5, respectively. These
      results exceed common risk benchmarks in the United States, suggesting a need for
      further studies to characterize VOC exposures, sources, and associated health
      risks in the Niger Delta.

PMID- 30200604
TI  - Modeling and Performance of the IEEE 802.11p Broadcasting for Intra-Platoon
      Communication.
AB  - Road capacity, traffic safety, and energy efficiency can be extremely improved by
      forming platoons with a small intra-vehicle spacing. Automated controllers obtain
      vehicle speed, acceleration, and position through vehicular ad hoc networks
      (VANETs), which allows the performance of platoon communication to make a
      significant impact on the stability of the platoon. To the best of our knowledge,
      there is not much research relating to packet delay and packet dropping rate of
      platoon communication based on the IEEE 802.11p broadcasting. In this paper, we
      introduce platoon structure model, vehicle control model, and communication model
      for a single platoon scenario. By utilizing Markov process and M/G/1/K queuing
      theory, we put forward an analytical model to assess the property of intra
      vehicle communication. The analytical model is validated by simulations and the
      influence of communication parameters on intra-vehicle communication performance
      are discussed. In addition, the experimental results demonstrate that the IEEE
      802.11p-based intra-vehicle communication guarantee the stability of platoon.

PMID- 30200603
TI  - "How Can the Patients Remain Safe, If We Are Not Safe and Protected from the
      Infections"? A Qualitative Exploration among Health-Care Workers about Challenges
      of Maintaining Hospital Cleanliness in a Resource Limited Tertiary Setting in
      Rural India.
AB  - Background: Health care-associated infections (HAIs) result in treatment delays
      as well as failures and financial losses not only to patients but also to the
      treating hospital and overall health-care delivery system. Due to hospital
      acquired infections, there are problems of increase in morbidity and mortality,
      additional diagnostic and therapeutic interventions and ultimately antimicrobial
      resistance. Proper understanding among health-care workers about the ill effects
      of HAIs is very important to address this issue. The present study is a
      qualitative exploration aimed at understanding various aspects of hospital
      environmental hygiene and Infection prevention control program, by exploring the
      staff perception regarding the challenges, facilitators and barriers as well as
      feasible measures towards improvement in a rural tertiary teaching hospital in
      central India. Method: A qualitative study was conducted using 10 focus group
      discussions (FGDs) among five different professional groups, which included
      hospital administrators, doctors, nurses, environmental cleaning staff, and
      undergraduate medical students. The FGD guide included the following topics: (1)
      opinion about the status of cleanliness, (2) concepts and actual practices
      prevailing of hospital environmental hygiene, (3) Barriers, constraints, and
      problems in maintaining hospital environmental hygiene, (4) Suggestions for
      improvements. The data were analyzed manually using the content (thematic)
      analysis method. Results: Two themes were identified: Theme 1: "Prevailing
      practices and problems related to hospital surface/object contamination and
      hospital infection control". Theme 2: "Measures suggested for improving hospital
      cleanliness within the existing constraints". The participants emphasized the
      influence of resource constraints and needed inputs. They brought up the
      consequent prevailing practices and problems related, on one hand, to various
      stakeholders (service consumers, hospital personnel including the management), on
      the other, to specific infection prevention and control processes. They also
      suggested various measures for improvement. Conclusions: The study has revealed
      prevailing practices, problems, and suggested measures related to hospital
      environmental hygiene, particularly hospital cleanliness and HAI prevention and
      control processes. These insights and assertions are important for developing
      future behavioral and structural interventions in resource-limited settings. This
      study recommends a nationwide reliable HAI surveillance system and a robust
      infection prevention and control program in each health-care institution.

PMID- 30200605
TI  - Mechanistic Insight into Etching Chemistry and HF-Assisted Etching of MgO-Al2O3
      SiO2 Glass-Ceramic.
AB  - The present study focuses on the etching conditions and mechanism of MgO-Al2O3
      SiO2 glass-ceramic (MAS) in hydrofluoric acid (HF). The results show that the
      amorphous phase has 218 times higher etching rate than pure cordierite crystal at
      room temperature. In addition, the activation energies of cordierite and
      amorphous phases in the HF solution are 52.5 and 30.6 kJ/mol, respectively. The
      time (tad) taken for complete dissolution of the amorphous phase depends on the
      HF concentration (CHF). Based on the etching experiments, a new model is
      established and refined to assess the tad evolution. In addition, a highly
      crystalline cordierite phase, with the high specific surface area (59.4 m2.g-1)
      and mesoporous structure, has been obtained by HF etching. This paper presents
      novel insights into the etching chemistry and opens up avenues for further
      research in the area of cordierite-based catalytic ceramics.

PMID- 30200606
TI  - Simultaneous Estimation of Rebar Diameter and Cover Thickness by a GPR-EMI Dual
      Sensor.
AB  - Precise characterization of reinforcing bars (rebars) in a concrete structure is
      of significant importance for construction quality control and post-disaster
      safety evaluation. This paper integrates ground-penetrating radar (GPR) and
      electromagnetic induction (EMI) methods for simultaneous estimation of rebar
      diameter and cover thickness. A prototype of GPR-EMI dual sensor is developed,
      and a calibration experiment is conducted to collect a standard EMI dataset
      corresponding to various rebar diameters and cover thicknesses. The handheld
      testing cart can synchronously collect both GPR and EMI data when moving on the
      concrete surface, from which a data processing algorithm is proposed to
      simultaneously estimate the rebar diameter and cover thickness. Firstly, by
      extracting the apex of the hyperbolic reflection from the rebar in the
      preprocessed GPR profile, the rebar position is determined and further used to
      extract the effective EMI curve. Then, the rebar diameter and cover thickness are
      simultaneously estimated from the minimum mean square error between the measured
      and calibrated EMI data under the constraint of the GPR-estimated cover
      thickness. A laboratory experiment is performed using four casted concrete
      specimens with 11 embedded steel rebars. The results show that the diameters of
      10 rebars are correctly estimated out of the 11 rebars, and the maximum
      estimation error for the cover thickness is 6.7%. A field trial is carried out in
      a newly-constructed building, and the diameters of four tested rebars are all
      accurately estimated while the estimation errors of the cover thickness are less
      than 5%. It is concluded that the developed GPR-EMI dual sensor and the proposed
      algorithm can estimate the rebar diameter and cover thickness accurately by a
      single scan.

PMID- 30200607
TI  - Atomistic Investigation of Anisotropic Nanoindentation Behavior of Nanotwinned
      Aluminum Containing Inclined Twin Boundaries.
AB  - Nanotwinned metals exhibit superior mechanical properties due to unique
      dislocation-twin boundary interactions. In the present work, we elucidate the
      microscopic deformation mechanisms and their correlations with the macroscopic
      mechanical response of nanotwinned Al containing inclined twin boundaries under
      nanoindentation by means of molecular dynamics simulations. The effect of twin
      boundary orientation with respect to the indented surface on the nanoindentation
      is evaluated. Simulation results reveal that dislocation slip, dislocation-twin
      boundary interaction, and twin boundary migration operate in parallel in the
      plastic deformation of nanotwinned Al. The inclination angle of twin boundaries
      with respect to indented surface has a strong influence on the interaction
      between individual deformation modes, which in turn leads to the anisotropic
      indentation behavior of nanotwinned Al.

PMID- 30200609
TI  - Monitoring and Evaluation Indicators for Climate Change-Related Health Impacts,
      Risks, Adaptation, and Resilience.
AB  - Climate change poses a range of current and future health risks that health
      professionals need to understand, track, and manage. However, conventional
      monitoring and evaluation (M&E) as practiced in the health sector, including the
      use of indicators, does not adequately serve this purpose. Improved indicators
      are needed in three broad categories: (1) vulnerability and exposure to climate
      related hazards; (2) current impacts and projected risks; and (3) adaptation
      processes and health system resilience. These indicators are needed at the
      population level and at the health systems level (including clinical care and
      public health). Selected indicators must be sensitive, valid, and useful. And
      they must account for uncertainties about the magnitude and pattern of climate
      change; the broad range of upstream drivers of climate-sensitive health outcomes;
      and the complexities of adaptation itself, including institutional learning and
      knowledge management to inform iterative risk management. Barriers and
      constraints to implementing such indicators must be addressed, and lessons
      learned need to be added to the evidence base. This paper describes an approach
      to climate and health indicators, including characteristics of the indicators,
      implementation, and research needs.

PMID- 30200608
TI  - Diabetes and Exposure to Environmental Lead (Pb).
AB  - Although the increased incidence of type 2 diabetes since the 1950s is thought to
      be primarily due to coincident alterations in lifestyle factors, another
      potential contributing factor in industrialized countries is exposure of the
      population to environmental pollutants and industrial chemicals. Exposure levels
      of many environmental toxicants have risen in the same time-frame as the disease
      incidence. Of particular interest in this regard is the metal lead. Although
      overall lead exposure levels have diminished in recent decades, there is an under
      recognized but persistent occurrence of lead exposure in poor underserved urban
      populations. Although the neural developmental pathologies induced by lead
      exposures have been well documented, very little is known about the effect of
      lead exposure on the incidence of chronic metabolic diseases such as type 2
      diabetes. Although our understanding of the metabolic health effects of lead
      exposure is incomplete, there are studies in model systems and a small amount of
      epidemiological data that together suggest a deleterious effect of environmental
      lead exposure on metabolic health. This article reviews the human, animal and in
      vitro studies that have examined the effects of lead exposure on the development
      of diabetes and related metabolic conditions.

PMID- 30200610
TI  - Application of Organo-Magadiites for the Removal of Eosin Dye from Aqueous
      Solutions: Thermal Treatment and Regeneration.
AB  - Na-magadiite exchanged with cetyl-trimethylammonium cations provided organophilic
      silicate materials that allowed for the effective removal of the acidic dye
      "eosin". The organic cations were intercalated into the interlayer spacing of the
      layered silicate via an exchange reaction between the organic cations from their
      bromide salt and the solid Na-magadiite at room temperature. Different techniques
      were used to characterize the effect of the initial concentration of the
      surfactant on the structure of the organo-magadiites. The C, H, and N analysis
      indicated that a maximum of organic cations of 0.97 mmol/g was achieved and was
      accompanied by an expansion of the basal spacing of 3.08 nm, with a tilted angle
      of 59 degrees  to the silicate layers. The conformation of the organic
      surfactants was probed using solid-state 13C, finding mainly the trans
      conformation similar to that of the starting cetyl trimethylammonium bromide salt
      (C16TMABr). Thermal gravimetric analysis was carried out to study the thermal
      stability of the resulting organo-magadiites. The intercalated surfactants
      started to decompose at 200  degrees C, with a mass loss percentage of 8% to 25%,
      depending on the initial loading of the surfactant, and was accompanied by a
      decrease of the basal spacing from 3.16 nm to 2.51 nm, as deduced from the in
      situ X-ray diffraction studies. At temperatures below 220  degrees C, an
      expansion of the basal spacing from 3.15 to 3.34 nm occurred. These materials
      were used as a removal agent for the anionic dye eosin. The maximum amount of the
      dye removed was related to the organic cation content and to the initial
      concentration of eosin, with an improvement from 2.5 mg/g to 80.65 mg/g. This
      value decreased when the organo-magadiite was preheated at temperatures above 200
      degrees C. The regeneration tests indicated that an 85% removal efficiency was
      maintained after six cycles of use for the organo-magadiite using Ci of 200 mg/L.

PMID- 30200611
TI  - Helical Structures Mimicking Chiral Seedpod Opening and Tendril Coiling.
AB  - Helical structures are ubiquitous in natural and engineered systems across
      multiple length scales. Examples include DNA molecules, plants' tendrils, sea
      snails' shells, and spiral nanoribbons. Although this symmetry-breaking shape has
      shown excellent performance in elastic springs or propulsion generation in a low
      Reynolds-number environment, a general principle to produce a helical structure
      with programmable geometry regardless of length scales is still in demand. In
      recent years, inspired by the chiral opening of Bauhinia variegata's seedpod and
      the coiling of plant's tendril, researchers have made significant breakthroughs
      in synthesizing state-of-the-art 3D helical structures through creating intrinsic
      curvatures in 2D rod-like or ribbon-like precursors. The intrinsic curvature
      results from the differential response to a variety of external stimuli of
      functional materials, such as hydrogels, liquid crystal elastomers, and shape
      memory polymers. In this review, we give a brief overview of the shape
      transformation mechanisms of these two plant's structures and then review recent
      progress in the fabrication of biomimetic helical structures that are categorized
      by the stimuli-responsive materials involved. By providing this survey on
      important recent advances along with our perspectives, we hope to solicit new
      inspirations and insights on the development and fabrication of helical
      structures, as well as the future development of interdisciplinary research at
      the interface of physics, engineering, and biology.

PMID- 30200613
TI  - Dme-Hsa Disease Database (DHDD): Conserved Human Disease-Related miRNA and Their
      Targeting Genes in Drosophila melanogaster.
AB  - Abnormal expressions of microRNA (miRNA) can result in human diseases such as
      cancer and neurodegenerative diseases. MiRNA mainly exert their biological
      functions via repressing the expression of their target genes. Drosophila
      melanogaster (D. melanogaster) is an ideal model for studying the molecular
      mechanisms behind biological phenotypes, including human diseases. In this study,
      we collected human and D. melanogaster miRNA as well as known human disease
      related genes. In total, we identified 136 human disease-related miRNA that are
      orthologous to 83 D. melanogaster miRNA by mapping "seed sequence", and 677 human
      disease-related genes that are orthologous to 734 D. melanogaster genes using the
      DRSC Integrative Ortholog Prediction Tool Furthermore, we revealed the target
      relationship between genes and miRNA using miRTarBase database and target
      prediction software, including miRanda and TargetScan. In addition, we visualized
      interaction networks and signalling pathways for these filtered miRNA and target
      genes. Finally, we compiled all the above data and information to generate a
      database designated DHDD This is the first comprehensive collection of human
      disease-related miRNA and their targeting genes conserved in a D. melanogaster
      database. The DHDD provides a resource for easily searching human disease-related
      miRNA and their disease-related target genes as well as their orthologs in D.
      melanogaster, and conveniently identifying the regulatory relationships among
      them in the form of a visual network.

PMID- 30200612
TI  - Serum Lipid Profile and Its Association with Diabetes and Prediabetes in a Rural
      Bangladeshi Population.
AB  - Dyslipidemia is commonly associated with diabetes (T2DM). This has been
      demonstrated for the Caucasian population, but few data are available for Asian
      Indians. The paper aims to investigate serum lipids (separately or in
      combination) and their association with glucose intolerance status (T2DM and
      prediabetes) in a rural Bangladeshi population. A sample of 2293 adults (>=20
      years) were included in a community based cross-sectional survey in 2009.
      Anthropometric measures, blood pressure, blood glucose (fasting and 2-h oral
      glucose tolerance test) and fasting serum lipids (total cholesterol, T-Chol;
      triglycerides, Tg; low density lipoprotein cholesterol, LDL-C and high density
      lipoprotein cholesterol, HDL-C) were registered. Analysis of covariance (ANCOVA)
      and regression analysis were performed. High Tg levels were seen in 26% to 64% of
      the participants, depending on glucose tolerance status. Low HDL-C levels were
      seen in all groups (>90%). Significant linear trends were observed for high T
      Chol, high Tg and low HDL-C with increasing glucose intolerance (p for trend
      <0.001). T2DM was significantly associated with high T-Chol (Odds ratio (OR):
      2.43, p < 0.001), high Tg (OR: 3.91, p < 0.001) and low HDL-C (OR: 2.17, p =
      0.044). Prediabetes showed a significant association with high Tg (OR: 1.96, p <
      0.001) and low HDL-C (OR: 2.93, p = 0.011). Participants with combined high Tg
      and low HDL-C levels had a 12.75-fold higher OR for T2DM and 4.89 OR for
      prediabetes. In Asian Indian populations an assessment of serum lipids is
      warranted not only for T2DM patients, but also for those with prediabetes.

PMID- 30200614
TI  - Biodiversity and Abundance of Cultured Microfungi from the Permanently Ice
      Covered Lake Fryxell, Antarctica.
AB  - In this work, we explore the biodiversity of culturable microfungi from the water
      column of a permanently ice-covered lake in Taylor Valley, Antarctica from
      austral field seasons in 2003, 2008 and 2010, as well as from glacial stream
      input (2010). The results revealed that there was a sharp decline in total
      culturable fungal abundance between 9 and 11 m lake depth with a concurrent shift
      in diversity. A total of 29 species were identified from all three water sources
      with near even distribution between Ascomycota and Basidomycota (15 and 14
      respectively). The most abundant taxa isolated from Lake Fryxell in 2008 were
      Glaciozyma watsonii (59%) followed by Penicillium spp. (10%), both of which were
      restricted to 9 m and above. Although seven species were found below the
      chemocline of 11 m in 2008, their abundance comprised only 10% of the total
      culturable fungi. The taxa of isolates collected from glacial source input
      streams had little overlap with those found in Lake Fryxell. The results
      highlight the spatial discontinuities of fungal populations that can occur within
      connected oligotrophic aquatic habitats.

PMID- 30200615
TI  - Development and Evaluation of Minocycline Hydrochloride-Loaded In Situ Cubic
      Liquid Crystal for Intra-Periodontal Pocket Administration.
AB  - In the present study, an injectable in situ liquid crystal formulation was
      developed for local delivery of minocycline hydrochloride (MH) for chronic
      periodontitis treatment. The physicochemical properties, phase structures, in
      vitro drug release and pharmacodynamics of in situ liquid crystals were
      investigated. The optimal formulation (phytantriol (PT)/propylene glycol
      (PG)/water, 63/27/10, w/w/w) loaded with 20 mg/g MH was proved to be injectable.
      The precursor formulation can form a cubic phase gel in excess water in 6.97 +/-
      0.10 s. The results of in vitro drug release suggested the MH presented a
      sustained release for 4 days. Liquid crystal precursor formulation significantly
      reduced gingival index, probing depth and alveolar bone loss compared to the
      model group (p < 0.01). Besides, the pathological characteristics of model rats
      were improved. The results suggested that MH-loaded in situ cubic liquid crystal
      possessed of sustained release ability and periodontal clinical symptoms
      improvement. The developed in situ cubic liquid crystal may be a potentially
      carrier in the local delivery of MH for periodontal diseases.

PMID- 30200616
TI  - Role of Ttca of Citrobacter Werkmanii in Bacterial Growth, Biocides Resistance,
      Biofilm Formation and Swimming Motility.
AB  - To screen, identify and study the genes involved in isothiazolone resistance and
      biofilm formation in Citrobacter werkmanii strain BF-6. A Tn5 transposon library
      of approximately 900 mutants of C. werkmanii strain BF-6 was generated and
      screened to isolate 1,2-benzisothiazolin-3-one (BIT) resistant strains. In
      addition, the tRNA 2-thiocytidine (32) synthetase gene (ttcA) was deleted through
      homologous recombination and the resulting phenotypic changes of the DeltattcA
      mutant were studied. A total of 3 genes were successfully identified, among which
      DeltattcA mutant exhibited a reduction in growth rate and swimming motility. On
      the other hand, an increase in biofilms formation in DeltattcA were observed but
      not with a significant resistance enhancement to BIT. This work, for the first
      time, highlights the role of ttcA gene of C. werkmanii strain BF-6 in BIT
      resistance and biofilm formation.

PMID- 30200617
TI  - Effect of Reverse-phase Transformation Annealing Process on Microstructure and
      Mechanical Properties of Medium Manganese Steel.
AB  - In order to develop a third-generation automobile steel with powerful strength
      and elongation, we propose a method through high temperature quenching and two
      phase region reverse-phase transformation annealing to develop such steel with
      0.13% C and 5.4% Mn. To investigate the microstructure evolution and mechanical
      properties of manganese steel, SEM, XRD and TEM are employed in our experiments.
      Experimental results indicate that the microstructure after quenching is mainly
      lath martensite microstructure with average of lath width at 0.5 MUm. The
      components of the steel after along with reverse-phase transformation annealing
      are ultra-fine grain ferrite, lath martensite and different forms of austenite
      microstructure. When the temperature at 625  degrees C, the components of the
      steel mainly includes lath martensite microstructure and ultra-fine grain ferrite
      and the fraction of austenite volume is only 5.09%. When the annealing
      temperature of reverse-phase transformation increase into 650  degrees C and 675 
      degrees C, the austenite appears in the boundary of the ferritic grain boundary
      and the boundary of lath martensite as the forms of bulk and lath. The phenomenon
      appears in the bulk of austenite, and the size of is 0.22 MUm, 0.3 MUm. The
      fraction of austenite volume is 22.34% at 675  degrees C and decreases into 9.32%
      at 700  degrees C. The components of austenite mainly includes ultra-fine grained
      ferrite and lath martensite. Furthermore, the density of decreases significantly,
      and the width of martensite increases into 0.32 MUm. In such experimental
      settings, quenching at 930  degrees C with 20 min and at 675  degrees C with 30
      min reverse-phase transformation annealing, the austenite volume fraction raises
      up to 22.34%.

PMID- 30200619
TI  - Graphene Oxide (GO)-Blended Polysulfone (PSf) Ultrafiltration Membranes for Lead
      Ion Rejection.
AB  - Graphene oxide (GO) has been widely reported and used for treatment of heavy
      metals from different waste streams. Although their use as additives for
      membranes has greatly enhanced membrane properties, there is still a bottleneck
      in obtaining membranes with high heavy-metal rejection efficiencies while
      maintaining high flux, mechanical strength, and porosity. In the present study,
      different compositions of GO (0-1 wt %)-blended membranes were prepared using 1
      methyl-2-pyrrolidone (NMP) as solvent and water with 5% ethanol as non-solvent,
      and studied for the rejection of the chosen model heavy-metal lead. The prepared
      membranes were characterized for hydrophilicity, membrane porosity, flux,
      permeability, pore-size, mechanical strength, and membrane morphology. From the
      results, it was inferred that membranes having maximum GO in their blend (1 wt %)
      showed better hydrophilicity (water contact angle 34.2 degrees ), porosity
      (82.2%), permeability (52.1 L/m2 h bar), and pure water flux (163.71 L/m2 h) at 3
      bar pressure as opposed to other compositions. The pore sizes of the membranes
      ranged between 18 to 24 nm. Tensile strength tests showed the role of GO as a
      positive reinforcement on the mechanical properties of membranes through Young's
      modulus (188.13 +/- 15.36 MPa) for the membrane having 0.25 wt % GO composition.
      Environmental Scanning Electron Microscopy (ESEM) images displayed the dense top
      layer supported by a porous, finger-like structure, obtained from instantaneous
      de-mixing favored by NMP and GO. The observed reduction in flux of lead solution
      for GO-blended membranes was due to osmotic pressure build-up caused by the
      retained nitrate salt by GO on the retentate side of the membrane. A maximum
      rejection of 98% was achieved with 1 wt % GO membrane at 1-bar pressure with flux
      of 43.62 L/m2 h, which decreased to 94% at 3-bar pressure with flux of 142.95
      L/m2 h. These results showed how the application of NMP as solvent and GO as an
      additive could facilitate in obtaining high-flux and high-rejection membranes.

PMID- 30200618
TI  - Myosin Head Configurations in Resting and Contracting Murine Skeletal Muscle.
AB  - Transgenic mouse models have been important tools for studying the relationship
      of genotype to phenotype for human diseases, including those of skeletal muscle.
      We show that mouse skeletal muscle can produce high quality X-ray diffraction
      patterns establishing the mouse intact skeletal muscle X-ray preparation as a
      potentially powerful tool to test structural hypotheses in health and disease. A
      notable feature of the mouse model system is the presence of residual myosin
      layer line intensities in contracting mouse muscle patterns. This provides an
      additional tool, along with the I1,1/I1,0 intensity ratio, for estimating the
      proportions of active versus relaxed myosin heads under a given set of conditions
      that can be used to characterize a given physiological condition or mutant muscle
      type. We also show that analysis of the myosin layer line intensity distribution,
      including derivation of the myosin head radius, Rm, may be used to study the role
      of the super-relaxed state in myosin regulation. When the myosin inhibitor
      blebbistatin is used to inhibit force production, there is a shift towards a
      highly quasi-helically ordered configuration that is distinct from the normal
      resting state, indicating there are more than one helically ordered configuration
      for resting crossbridges.

PMID- 30200620
TI  - Low Infection of Phelipanche aegyptiaca in Micro-Tom Mutants Deficient in
      CAROTENOIDCLEAVAGE DIOXYGENASE 8.
AB  - Strigolactones (SLs), a group of plant hormones, induce germination of root
      parasitic plants and inhibit shoot branching in many plants. Shoot branching is
      an important trait that affects the number and quality of flowers and fruits.
      Root-parasitic plants, such as Phelipanche spp., infect tomato roots and cause
      economic damage in Europe and North Africa-hence why resistant tomato cultivars
      are needed. In this study, we found carotenoid cleavage dioxygenase 8-defective
      mutants of Micro-Tom tomato (slccd8) by the "targeting induced local lesions in
      genomes" (TILLING) method. The mutants showed excess branching, which was
      suppressed by exogenously applied SL. Grafting shoot scions of the slccd8 mutants
      onto wild-type (WT) rootstocks restored normal branching in the scions. The
      levels of endogenous orobanchol and solanacol in WT were enough detectable,
      whereas that in the slccd8 mutants were below the detection limit of
      quantification analysis. Accordingly, root exudates of the slccd8 mutants hardly
      stimulated seed germination of root parasitic plants. In addition, SL deficiency
      did not critically affect the fruit traits of Micro-Tom. Using a rhizotron
      system, we also found that Phelipanche aegyptiaca infection was lower in the
      slccd8 mutants than in wild-type Micro-Tom because of the low germination. We
      propose that the slccd8 mutants might be useful as new tomato lines resistant to
      P. aegyptiaca.

PMID- 30200621
TI  - Developing an Awareness Campaign to Reduce Second Hand Smoke Among Disadvantaged
      Families-A Participatory M-Health Approach.
AB  - Children from disadvantaged families are particularly exposed to second hand
      smoke in their home environment. Using a mixed methods participatory approach, we
      aimed at identifying suitable media channels and appropriate content for a
      campaign increasing caregivers' knowledge about the risks of second hand smoke
      (SHS) exposure for their children and appropriate measures for exposure
      reduction. In the first phase of the mixed method design, we evaluated knowledge
      and norms about children's SHS and perceived barriers for avoiding it. To this
      end, we conducted 26 one-to-one interviews with smoking caregivers of children
      below the age of six years. Subsequently, we developed and illustrated core
      messages and identified appropriate communication channels. These were evaluated
      in focus group discussions by 20 of the 26 interview participants. After a final
      revision, 121 caregivers evaluated the campaign via an online questionnaire.
      Online social networks were identified as the most suitable media channel. For
      these, we developed animated photos with voiceovers addressing the potential
      consequences of SHS for children. The overall rating of the campaign messages was
      promising. Participants confirmed that it was important to address the issue in
      social media. However, sharing the pictures was considered unlikely due to the
      sensitive topic of the campaign, while the importance of doctors or scientists
      being recognizable as a source was highlighted. Employing a participatory
      approach, we developed an m-health campaign, which can now be disseminated in
      social networks to reach the target population. The effectiveness of the campaign
      should be evaluated.

PMID- 30200622
TI  - Effects of Heating Mode and Temperature on the Microstructures, Electrical and
      Optical Properties of Molybdenum Thin Films.
AB  - In this paper, molybdenum (Mo) thin films are deposited on soda-lime glass (SLG)
      substrates by direct current magnetron sputtering and heated in three different
      modes at different temperatures, including substrate heating, annealing
      treatment, and both substrate heating and annealing treatment. The effects of
      heating temperature and heating mode on the structures, morphology, optical and
      electrical properties of Mo thin films were systematically investigated by X-ray
      diffraction (XRD), Scanning electron microscopy (SEM), atomic force microscope
      (AFM) and UV-visible spectrophotometer (UV-vis spectra). It is shown that as the
      substrate and annealing temperature increase, the crystallinity of Mo thin films
      is improved, and the grain sizes become bigger. Especially in the mode of both
      substrate heating and annealing treatment at higher temperature, the obtained Mo
      thin films show higher crystallinity and conductivity. Moreover, with the
      increase of substrate and annealing temperature in different heating modes, both
      the surface compactness of Mo films and the optical reflectance increase
      correspondingly. Furthermore, the Mo film, prepared at the substrate heating
      temperature of 400  degrees C and annealed at 400  degrees C, showed excellent
      comprehensive performance, and the resistivity is as low as 1.36 * 10-5 Omega.cm.
      Using this optimized Mo thin film as an electrode, copper indium gallium selenium
      (CIGS) solar cells have a maximum photo-conversion efficiency of 12.8%.

PMID- 30200624
TI  - Wireless Sensor Network Localization via Matrix Completion Based on Bregman
      Divergence.
AB  - One of the main challenges faced by wireless sensor network (WSN) localization is
      the positioning accuracy of the WSN node. The existing algorithms are arduous to
      use for dealing with the pulse noise that is universal and ineluctable in
      practical considerations, resulting in lower positioning accuracy. Aimed at this
      problem and introducing Bregman divergence, we propose in this paper a novel WSN
      localization algorithm via matrix completion (LBDMC). Based on the natural low
      rank character of the Euclidean Distance Matrix (EDM), the problem of EDM
      recovery is formulated as an issue of matrix completion in a noisy environment. A
      regularized matrix completion model is established, smoothing the pulse noise by
      leveraging L 1 , 2 -norm and the multivariate function Bregman divergence is
      defined to solve the model to obtain the EDM estimator. Furthermore, node
      localization is available based on the multi-dimensional scaling (MDS) method.
      Multi-faceted comparison experiments with existing algorithms, under a variety of
      noise conditions, demonstrate the superiority of LBDMC to other algorithms
      regarding positioning accuracy and robustness, while ensuring high efficiency.
      Notably, the mean localization error of LBDMC is about ten times smaller than
      that of other algorithms when the sampling rate reaches a certain level, such as
      >30%.

PMID- 30200623
TI  - Mother-Infant Physical Contact Predicts Responsive Feeding among U.S.
      Breastfeeding Mothers.
AB  - Responsive feeding-initiating feeding in response to early hunger cues-supports
      the physiology of lactation and the development of infant feeding abilities, yet
      there is a dearth of research examining what predicts responsive feeding. In non
      Western proximal care cultures, there is an association between responsive
      feeding and mother-infant physical contact, but this has not been investigated
      within Western populations. In two studies, we tested whether mother-infant
      physical contact predicted feeding in response to early hunger cues versus
      feeding on a schedule or after signs of distress among U.S. breastfeeding
      mothers. With an online questionnaire in Study 1 (n = 626), physical contact with
      infants (via co-sleeping and babywearing) predicted increased likelihood of self
      reported responsive feeding. Mothers who reported responsive feeding were more
      likely to exclusively breastfeed for the first six months, breastfeed more
      frequently throughout the day, and had a longer planned breastfeeding duration
      than mothers who reported feeding on a schedule or after signs of infant
      distress. In Study 2 (n = 96), a three-day feeding log showed that mother-infant
      physical contact predicted feeding in response to early hunger cues but mother
      infant proximity (without physical contact) did not. In sum, our results
      demonstrate that physical contact with infants may shape breastfeeding behavior
      among U.S. mothers, highlighting a connection between social interaction and
      infant nutrition that warrants further investigation.

PMID- 30200625
TI  - Design, Synthesis and Biological Evaluation of Novel 4-Substituted Coumarin
      Derivatives as Antitumor Agents.
AB  - Herein, fifteen new compounds containing coumarin, 1,2,3-triazole and benzoyl-
      substituted arylamine moieties were designed, synthesized and tested in vitro for
      their anticancer activity. The results showed that all tested compounds had
      moderate antiproliferative activity against MDA-MB-231, a human breast cancer
      cell line, under both normoxic and hypoxic conditions. Furthermore, the 4
      substituted coumarin linked with benzoyl 3,4-dimethoxyaniline through 1,2,3
      triazole (compound 5e) displayed the most prominent antiproliferative activities
      with an IC50 value of 0.03 MUM, about 5000 times stronger than 4-hydroxycoumarin
      (IC50 > 100 MUM) and 20 times stronger than doxorubicin (IC50 = 0.60 MUM).
      Meanwhile, almost all compounds revealed general enhancement of proliferation
      inhibiting activity under hypoxia, contrasted with normoxia. A docking analysis
      showed that compound 5e had potential to inhibit carbonic anhydrase IX (CA IX).

PMID- 30200626
TI  - Unsupervised Hierarchical Clustering Approach for Tourism Market Segmentation
      Based on Crowdsourced Mobile Phone Data.
AB  - Understanding tourism related behavior and traveling patterns is an essential
      element of transportation system planning and tourism management at tourism
      destinations. Traditionally, tourism market segmentation is conducted to
      recognize tourist's profiles for which personalized services can be provided.
      Today, the availability of wearable sensors, such as smartphones, holds the
      potential to tackle data collection problems of paper-based surveys and deliver
      relevant mobility data in a timely and cost-effective way. In this paper, we
      develop and implement a hierarchical clustering approach for smartphone geo
      localized data to detect meaningful tourism related market segments. For these
      segments, we provide detailed insights into their characteristics and related
      mobility behavior. The applicability of the proposed approach is demonstrated on
      a use case in the Province of Zeeland in the Netherlands. We collected data from
      1505 users during five months using the Zeeland app. The proposed approach
      resulted in two major clusters and four sub-clusters which we were able to
      interpret based on their spatio-temporal patterns and the recurrence of their
      visiting patterns to the region.

PMID- 30200628
TI  - First Aid Practices and Health-Seeking Behaviors of Caregivers for Unintentional
      Childhood Injuries in Ujjain, India: A Community-Based Cross-Sectional Study.
AB  - Data on types of community first aid use and treatment provided post-injury from
      many low-middle-income countries, including India, are lacking. This cross
      sectional study was conducted among children aged one month to 18 years of age,
      in Ujjain, India, to understand types of first aid given and health-seeking post
      injury. A total of 1087 injuries in 1049 children were identified in the past
      year. A total of 729 (67%) injured children received first aid and 758 (70%)
      sought some form of health care. Children with burns received the most (86%)
      first aid, and most children (84%) with road traffic accidents (RTA) sought
      health care. Most children (52%) sought health care from a private health care
      facility; most children (65%) were transported to a health care facility within
      the golden hour. Motorbikes were the most preferred (50%) mode of transport. Only
      1% of the injured used ambulance services. Commonly reported methods or
      substances for first aid included the use of coconut oil on wounds from falls
      (38%) and burns (44%), the use of antiseptic cream on wounds from RTA (31%), the
      application of turmeric for wounds from falls (16%), and rubbing of metal on a
      bitten area (47%). For most injuries, appropriate, locally available substances
      were used. Potentially harmful substances applied included lime, toothpaste,
      clay, and mud. The findings will help design community interventions to increase
      the provision of appropriate first aid for childhood injuries.

PMID- 30200627
TI  - Short-Term Fish Oil Treatment Changes the Composition of Phospholipids While Not
      Affecting the Expression of Mfsd2a Omega-3 Transporter in the Brain and Liver of
      the 5xFAD Mouse Model of Alzheimer's Disease.
AB  - Long-term fish oil (FO) supplementation is able to improve Alzheimer's disease
      (AD) pathology. We aimed to determine the impact of short-term fish oil (FO)
      intake on phospholipids composition and plaque pathology in 5xFAD mice, a widely
      used animal model of AD. A 3-week-long FO supplementation administered at 3
      months of age decreased the number of dense core plaques in the 5xFAD cortex and
      changed phospholipids in the livers and brains of wild-type (Wt) and 5xFAD mice.
      Livers of both genotypes responded by increase of n-3 and reciprocal decrease of
      n-6 fatty acids. In Wt brains, FO supplementation induced elevation of n-3 fatty
      acids and subsequent enhancement of n-6/n-3 ratio. However, in 5xFAD brains the
      improved n-6/n-3 ratio was mainly due to FO-induced decrease in arachidonic and
      adrenic n-6 fatty acids. Also, brain and liver abundance of n-3 fatty acids were
      strongly correlated in Wts, oppositely to 5xFADs where significant brain-liver
      correlation exists only for n-6 fatty acids. Expression of omega-3 transporter
      Mfs2a remained unchanged after FO supplementation. We have demonstrated that even
      a short-term FO intake improves the phospholipid composition and has a
      significant effect on plaque burden in 5xFAD brains when applied in early stages
      of AD pathology.

PMID- 30200629
TI  - Can Genetic Factors Compromise the Success of Dental Implants? A Systematic
      Review and Meta-Analysis.
AB  - Dental implants provide a predictable treatment option for partial and complete
      edentulism via the placement of a fixed permanent artificial root to support
      prosthetic dental crowns. Despite the high survival rates, long-term dental
      implant failures are still reported, leading to implant removals and additional
      financial and health burdens. While extrinsic factors that improve the success
      rate of implants have been well explored, the impact of genetic factors on this
      matter is poorly understood. A systematic review and meta-analysis study was
      conducted to determine whether genetic factors contribute to an increased risk of
      dental implant failures. A comprehensive search for peer-reviewed articles on
      dental implants and genetic factors was performed using various literature
      database libraries. The study design was conducted according to Preferred
      Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, and
      the obtained records were registered in the International Prospective Register of
      Systematic Reviews (PROSPERO) database. According to the exclusion/inclusion
      criteria, 13 studies were eligible for this study out of 809 articles. The meta
      analysis of the combined association studies of DNA variations and dental
      implants did not indicate an increased risk for implant failure due to DNA
      variations in IL-1B, IL-10 and TNF-alpha. This study emphasizes the need for
      larger randomized controlled clinical trials to inform clinicians and patients
      about the role of genetic factors on dental implant survival and the success rate
      in healthy and compromised patients.

PMID- 30200630
TI  - PTPRT and PTPRD Deleterious Mutations and Deletion Predict Bevacizumab Resistance
      in Metastatic Colorectal Cancer Patients.
AB  - BACKGROUND: Bevacizumab-based regimens are used as standard treatments for
      colorectal cancer. Unfortunately, there are no established predictive markers for
      bevacizumab response. METHODS: Tumor samples from 36 metastatic colorectal cancer
      patients treated with bevacizumab plus chemotherapy were analyzed by next
      generation sequencing of all coding exons of more than 400 genes. Single gene and
      signaling pathway analyses were performed to correlate genomic data with
      response. RESULTS: Among the genes most frequently mutated in our cohort, only
      mutations in PTPRT, a phosphatase involved in JAK/STAT signaling, were associated
      with response status, with deleterious mutations being enriched in non
      responders. Pathway analysis revealed that deleterious mutations in genes of the
      JAK/STAT pathway, namely in PTPRT and the related gene PTPRD, correlated with
      resistance. Mutations in RTK/PI3K/RAS, Wnt and TGFbeta pathways did not associate
      with response. Lack of response was observed in all patients with deleterious
      mutations or copy number loss of PTPRT/PTPRD (n = 10), compared to only 30.8% (n
      = 8) of patients without such alterations (relative risk, 3.25; 95% CI, 1.83
      5.79, p = 0.0003). Similarly, PTPRT/PTPRD deleterious alterations were associated
      with shorter progression-free survival, an association that was retained in
      multivariate analysis (HR, 3.33; 95% CI, 1.47-7.54; p = 0.0038). CONCLUSION:
      Deleterious alterations in PTPRT/PTPRD are potential biomarkers for bevacizumab
      resistance.

PMID- 30200633
TI  - The Coupling Effect of O2 and H2S on the Corrosion of G20 Steel in a Simulating
      Environment of Flue Gas Injection in the Xinjiang Oil Field.
AB  - Flue gas injection for heavy oil recovery has received a great deal of attention,
      because it is more cost effective than lots of other injection methods. However,
      the corrosion could occur easily, because the flue gas usually contains corrosive
      gases such as CO2, H2S, and O2. In this work, the corrosion behaviors of G20
      steel in flue gas injection environment simulating Xinjiang oil field (China)
      were investigated using weight loss measurement and surface characterization
      techniques. The effect of environments including the O2-containing environment,
      the H2S-containing environment, and the O2-H2S-coexisting environment on the
      corrosion of G20 steel in gas phase and liquid phase was discussed. The results
      show that the corrosion rate of G20 steel in the O2-H2S-coexisting environment is
      much higher than the sum of corrosion rates of the O2-containing environment and
      the H2S-containing environment, regardless of the gas phase and the liquid phase.
      This indicates that there is a coupling effect between O2 and H2S, which can
      further accelerate the corrosion of steel in O2-H2S-coexisting environment. The
      results of surface characterization demonstrate that in a typical flue gas
      injection environment, the corrosion products are composed of FeCO3, FeS,
      FeO(OH), and elemental sulfur. Elemental sulfur could obviously accelerate the
      corrosion of steel. Therefore, it can be considered that the coupling effect of
      O2 and H2S on corrosion of G20 steel in flue gas injection environment is caused
      by the formation of elemental sulfur in corrosion products.

PMID- 30200632
TI  - Dietary Patterns and Breast Cancer Risk: A Multi-Centre Case Control Study among
      North Indian Women.
AB  - Evidence from India, a country with unique and distinct food intake patterns
      often characterized by lifelong adherence, may offer important insight into the
      role of diet in breast cancer etiology. We evaluated the association between
      Indian dietary patterns and breast cancer risk in a multi-centre case-control
      study conducted in the North Indian states of Punjab and Haryana. Eligible cases
      were women 30-69 years of age, with newly diagnosed, biopsy-confirmed breast
      cancer recruited from hospitals or population-based cancer registries. Controls
      (hospital- or population-based) were frequency matched to the cases on age and
      region (Punjab or Haryana). Information about diet, lifestyle, reproductive and
      socio-demographic factors was collected using a structured interviewer
      administered questionnaire. All participants were characterized as non
      vegetarians, lacto-vegetarians (those who consumed no animal products except
      dairy) or lacto-ovo-vegetarians (persons whose diet also included eggs). The
      study population included 400 breast cancer cases and 354 controls. Most (62%)
      were lacto-ovo-vegetarians. Breast cancer risk was lower in lacto-ovo-vegetarians
      compared to both non-vegetarians and lacto-vegetarians with odds ratios (95%
      confidence intervals) of 0.6 (0.3-0.9) and 0.4 (0.3-0.7), respectively. The
      unexpected difference between lacto-ovo-vegetarian and lacto-vegetarian dietary
      patterns could be due to egg-consumption patterns which requires confirmation and
      further investigation.

PMID- 30200631
TI  - Maternal Stress Potentiates the Effect of an Inflammatory Diet in Pregnancy on
      Maternal Concentrations of Tumor Necrosis Factor Alpha.
AB  - Maternal inflammation during pregnancy is known to adversely impact fetal
      development, birth outcomes, and offspring physical and mental health. Diet and
      stress have been identified as important determinants of inflammation, yet their
      combined effects have not been examined in the context of pregnancy. The aim of
      this study was to examine the relationship between maternal diet with
      inflammatory potential and psychological stress, and to determine their
      interaction effect on concentrations of tumor necrosis factor (TNF)-alpha across
      pregnancy. We conducted a prospective longitudinal study of n = 202 women with
      three assessments during pregnancy, which included: ecological momentary
      assessment (EMA) of maternal stress using the perceived stress scale (PSS) short
      version; 24-h dietary recalls from which the dietary inflammatory index (DII) was
      computed; and serum measurements of TNF-alpha. Across pregnancy, higher perceived
      stress was associated with consumption of a more pro-inflammatory diet (r =
      0.137; p < 0.05). In a linear regression model adjusted for covariates, DII was
      positively associated with TNF-alpha (B = 0.093, p = 0.010). The effect of the
      pro-inflammatory diet on concentrations of TNF-alpha was more pronounced in women
      reporting higher levels of stress (B = 0.134, p = 0.018 for DII*PSS interaction).
      These results highlight the need to consider nutrition and stress concurrently in
      the context of inflammation during pregnancy.

PMID- 30200634
TI  - Translational Acceleration, Rotational Speed, and Joint Angle of Patients Related
      to Correct/Incorrect Methods of Transfer Skills by Nurses.
AB  - Currently, due to shortages in the nursing faculty and low access to actual
      patients, it is difficult for students to receive feedback from teachers and
      practice with actual patients to obtain clinic experience. Thus, both evaluation
      systems and simulated patients have become urgent requirements. Accordingly, this
      study proposes a method to evaluate the nurse's transfer skill through
      observation from the patient. After verifying the proposed method, it will be
      integrated with a robotic patient as a future work. To verify if such an
      evaluation is practical, a checklist comprising 16 steps with correct and
      incorrect methods was proposed by the nursing teachers. Further, the evaluation
      parameters were determined as translational acceleration, rotational speed, and
      joint angle of patient. Inertial sensors and motion capture were employed to
      measure the translational acceleration, rotational speed, and joint angle. An
      experiment was conducted with two nursing teachers, who were asked to carry out
      both correct and incorrect methods. According to the results, three parameters
      reveal the difference for a patient under correct/incorrect methods and can
      further be used to evaluate the nurse's skill once the thresholds are determined.
      In addition, the applicability of inertial sensors is confirmed for the use of
      robot development.

PMID- 30200635
TI  - Could miRNA Signatures be Useful for Predicting Uterine Sarcoma and
      Carcinosarcoma Prognosis and Treatment?
AB  - Changes in microRNA (miRNA) expression may lead to cancer development and/or
      contribute to its progression; however, their role in uterine sarcomas is poorly
      understood. Uterine sarcomas (US) belong to a rare class of heterogeneous tumors,
      representing about 1% of all gynecologic neoplasms. This study aimed to assess
      the expression profile of 84 cancer-related miRNAs and to evaluate their
      correlation with clinical pathological features. Eighty-two formalin-fixed
      paraffin-embedded (FFPE) samples were selected. In leiomyosarcoma (LMS), there
      was an association of lower cancer-specific survival (CSS) with the
      downregulation of miR-125a-5p and miR-10a-5p, and the upregulation of miR-196a-5p
      and miR-34c-5p. In carcinosarcoma (CS), lower CSS was associated with the
      upregulation of miR-184, and the downregulation of let-7b-5p and miR-124. In
      endometrial stromal sarcomas (ESS), the upregulation of miR-373-3p, miR-372-3p,
      and let-7b-5p, and the down-expression of let-7f-5p, miR-23-3p, and let-7b-5p
      were associated with lower CSS. Only miR-138-5p upregulation was associated with
      higher survival rates. miR-335-5p, miR-301a-3p, and miR-210-3p were more highly
      expressed in patients with tumor metastasis and relapse. miR-138-5p, miR-146b-5p,
      and miR-218-5p expression were associated with higher disease-free survival (DFS)
      in treated patients. These miRNAs represent potential prediction markers for
      prognosis and treatment response in these tumors.

PMID- 30200637
TI  - Globally Optimal Distributed Kalman Filtering for Multisensor Systems with
      Unknown Inputs.
AB  - In this paper, the state estimation for dynamic system with unknown inputs
      modeled as an autoregressive AR (1) process is considered. We propose an optimal
      algorithm in mean square error sense by using difference method to eliminate the
      unknown inputs. Moreover, we consider the state estimation for multisensor
      dynamic systems with unknown inputs. It is proved that the distributed fused
      state estimate is equivalent to the centralized Kalman filtering using all sensor
      measurement; therefore, it achieves the best performance. The computation
      complexity of the traditional augmented state algorithm increases with the
      augmented state dimension. While, the new algorithm shows good performance with
      much less computations compared to that of the traditional augmented state
      algorithms. Moreover, numerical examples show that the performances of the
      traditional algorithms greatly depend on the initial value of the unknown inputs,
      if the estimation of initial value of the unknown input is largely biased, the
      performances of the traditional algorithms become quite worse. However, the new
      algorithm still works well because it is independent of the initial value of the
      unknown input.

PMID- 30200636
TI  - Metagenomic Composition Analysis of an Ancient Sequenced Polar Bear Jawbone from
      Svalbard.
AB  - The sequencing of ancient DNA samples provides a novel way to find, characterize,
      and distinguish exogenous genomes of endogenous targets. After sequencing,
      computational composition analysis enables filtering of undesired sources in the
      focal organism, with the purpose of improving the quality of assemblies and
      subsequent data analysis. More importantly, such analysis allows extinct and
      extant species to be identified without requiring a specific or new sequencing
      run. However, the identification of exogenous organisms is a complex task, given
      the nature and degradation of the samples, and the evident necessity of using
      efficient computational tools, which rely on algorithms that are both fast and
      highly sensitive. In this work, we relied on a fast and highly sensitive tool,
      FALCON-meta, which measures similarity against whole-genome reference databases,
      to analyse the metagenomic composition of an ancient polar bear (Ursus maritimus)
      jawbone fossil. The fossil was collected in Svalbard, Norway, and has an
      estimated age of 110,000 to 130,000 years. The FASTQ samples contained 349 GB of
      nonamplified shotgun sequencing data. We identified and localized, relative to
      the FASTQ samples, the genomes with significant similarities to reference
      microbial genomes, including those of viruses, bacteria, and archaea, and to
      fungal, mitochondrial, and plastidial sequences. Among other striking features,
      we found significant similarities between modern-human, some bacterial and viral
      sequences (contamination) and the organelle sequences of wild carrot and tomato
      relative to the whole samples. For each exogenous candidate, we ran a damage
      pattern analysis, which in addition to revealing shallow levels of damage in the
      plant candidates, identified the source as contamination.

PMID- 30200638
TI  - RBM4a-SRSF3-MAP4K4 Splicing Cascade Constitutes a Molecular Mechanism for
      Regulating Brown Adipogenesis.
AB  - An increase in mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4)
      reportedly attenuates insulin-mediated signaling which participates in the
      development of brown adipose tissues (BATs). Nevertheless, the effect of MAP4K4
      on brown adipogenesis remains largely uncharacterized. In this study, results of
      a transcriptome analysis (also referred as RNA-sequencing) showed differential
      expressions of MAP4K4 or SRSF3 transcripts isolated from distinct stages of
      embryonic BATs. The discriminative splicing profiles of MAP4K4 or SRSF3 were
      noted as well in brown adipocytes (BAs) with RNA-binding motif protein 4-knockout
      (RBM4-/-) compared to the wild-type counterparts. Moreover, the relatively high
      expressions of authentic SRSF3 transcripts encoding the splicing factor
      functioned as a novel regulator toward MAP4K4 splicing during brown adipogenesis.
      The presence of alternatively spliced MAP4K4 variants exerted differential
      effects on the phosphorylation of c-Jun N-terminal protein kinase (JNK) which was
      correlated with the differentiation or metabolic signature of BAs. Collectively,
      the RBM4-SRSF3-MAP4K4 splicing cascade constitutes a novel molecular mechanism in
      manipulating the development of BAs through related signaling pathways.

PMID- 30200640
TI  - A Novel Fluoride Containing Bioactive Glass Paste is Capable of Re-Mineralizing
      Early Caries Lesions.
AB  - : White-spot-lesions (WSL) are a common complication associated with orthodontic
      treatment. In the current study, the remineralization efficacy of a BiominF(r)
      paste was compared to the efficacy of a fluoride gel. METHODS: Orthodontic
      brackets were bonded to 60 human premolars buccal surfaces, which were covered
      with varnish, except a small treatment area (3 mm2). All specimens were
      challenged by a demineralization solution for 4 days. Specimens were assigned
      into 4 groups: BiominF(r) paste, Fluoride (4-min application), fluoride (twenty
      four hours application), and the control (n = 15). After cross-sectioning, enamel
      slabs having a thickness of approximately 100-120 MUm were obtained. A TMR
      (Transverse Micro Radiography) technique was used to observe the sub-surface
      enamel lesions' depth and mineral density, and their response to the
      remineralization protocols. One way ANOVA was used to analyze the results (alpha
      = 0.05). The top and the cross-sectional surfaces were observed using SEM/EDS.
      RESULTS: Specimens treated with BiominF(r) paste showed significant decrease in
      delta z values, however lesion depth showed no significant difference when
      compared to the other three groups (p < 0.05). SEM/EDS observation showed the
      formation of crystal like structures on top of enamel demineralized surfaces,
      when treated with BiominF(r) paste. In conclusion BiominF(r) paste can be
      considered an effective remineralizing agent for white spot Lesions.

PMID- 30200639
TI  - Standardization of G. mellonella Larvae to Provide Reliable and Reproducible
      Results in the Study of Fungal Pathogens.
AB  - In the past decade, Galleria mellonella (wax moth) larvae have become widely used
      as a non-mammalian infection model. However, the full potential of this infection
      model has yet to be realised, limited by the variable quality of larvae used and
      the lack of standardised procedures. Here, we review larvae suitable for
      research, protocols for dosing larvae, and methods for scoring illness in larvae
      infected with fungal pathogens. The development of standardised protocols for
      carrying out our experimental work will allow high throughput screens to be
      developed, changing the way in which we evaluate panels of mutants and strains.
      It will also enable the in vivo screening of potential antimicrobials at an
      earlier stage in the research and development cycle.

PMID- 30200641
TI  - Stimulation of the Production of Prostaglandin E2 by Ethyl Gallate, a Natural
      Phenolic Compound Richly Contained in Longan.
AB  - Ethyl gallate is a phenolic compound richly contained in Longan. In traditional
      Chinese medicine, Longan is widely known as a fruit with "hot" properties, with a
      tendency to promote inflammatory and certain other responses. The mechanism for
      its proinflammatory as well as health beneficial effects is poorly understood.
      Based on our earlier observation that certain natural phenolic compounds can
      serve as reducing cosubstrates for cyclooxygenases (COXs), we sought to test a
      hypothesis that ethyl gallate may activate the catalytic activity of the COX
      enzymes. Results from studies using cultured cells and animals show that ethyl
      gallate can activate the production of prostaglandin E2, a representative
      prostaglandin tested in this study. Computational analysis indicates that ethyl
      gallate can activate the peroxidase active sites of COX-1 and COX-2 by serving as
      a reducing cosubstrate. The effect of ethyl gallate is abrogated by galangin,
      which is known to bind to the same peroxidase active sites of COX-1 and COX-2 as
      a competitive inhibitor. The findings of this study offer support for a novel
      hypothesis that the proinflammatory as well as health beneficial effects of
      Longan may partly attributable to the activation of COX-1 and COX-2 by ethyl
      gallate.

PMID- 30200642
TI  - Lead in Air in Bangladesh: Exposure in a Rural Community with Elevated Blood Lead
      Concentrations among Young Children.
AB  - Previous evaluations of a birth cohort in the Munshiganj District of Bangladesh
      had found that over 85% of 397 children aged 2-3 years had blood lead
      concentrations above the United States Centers for Disease Control and
      Prevention's reference level of 5 MUg/dL. Studies in urban areas of Bangladesh
      have found elevated levels of lead in the air due to industries and remaining
      contamination from the historic use of leaded gasoline. Sources of lead in rural
      areas of Bangladesh remain unknown. We conducted air sampling in both residential
      and industrial sites in Munshiganj to determine whether children are exposed to
      elevated lead concentrations in the air and study the association between the
      children's blood lead levels and sampled air lead concentrations. Residential and
      industrial air samples in Munshiganj were found to have elevated lead
      concentrations (mean 1.22 MUg/m3) but were not found to be associated with the
      observed blood lead concentrations. Lead in air is an important environmental
      health exposure risk to the for children in Munshiganj, and further research may
      shed light on specific sources to inform exposure prevention and mitigation
      programs.

PMID- 30200643
TI  - Bioactive Phytochemicals and Antioxidant Properties of the Grains and Sprouts of
      Colored Wheat Genotypes.
AB  - The grains and sprouts of colored wheat genotypes (having blue, purple and yellow
      colored grains) contain specific anthocyanidins, such as pelargonidin and
      cyanidin derivatives, that produce beneficial health effects. The objective of
      the presented study is to compare the antioxidant capacity and contents of
      bioactive phytochemicals in grains and sprouts of wheat genotypes that differ in
      grain color. The methods alpha, alpha-diphenyl-beta-picrylhydrazyl (DPPH) and
      2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) scavenging
      activities, together with spectrophotometrical and high-performance thin-layer
      chromatography (HPTLC) methods, were used to study the presence of total
      phenolics, flavonoids, anthocyanins and anthocyanidins (pelargonidin, peonidin,
      cyanidin, delphinidin) content. It was predicted that the sprouts of all colored
      wheat genotypes would have significantly higher total flavonoids, total
      phenolics, anthocyanidin levels and antioxidant activity than the grains. The
      correlation results between antioxidant activity and contents of bioactive
      phytochemicals in grains and sprouts of colored wheat genotypes have shown a high
      correlation for cyanidin and pelargonidin, especially in grains, as well as
      quercetin in sprouts. It was found that total anthocyanin, quercetin and
      pelargonidin contents were significantly higher in the sprouts of the purple
      wheat genotypes than in the blue or yellow wheat genotypes. Delphinidin was
      detected at a higher level in the grains than in the sprouts of the blue wheat
      genotypes. Peonidin was present at very low quantities in the grains of all
      colored wheat genotypes. The sprouts of the purple wheat genotypes, among the
      colored wheat genotypes, had the highest pelargonidin, cyanidin and quercetin
      contents and, therefore, can be a promising source for functional food use.

PMID- 30200644
TI  - PDGFR and IGF-1R Inhibitors Induce a G2/M Arrest and Subsequent Cell Death in
      Human Glioblastoma Cell Lines.
AB  - Glioblastomas are highly resistant to radiation and chemotherapy. Currently,
      there are no effective therapies for this type of tumor. Signaling mechanisms
      initiated by PDGFR and IGF-1R are important in glioblastoma, and inhibition of
      the signal transduction pathways initiated by these receptors could be a useful
      alternative strategy for glioblastoma treatment. We have studied the effects of
      the PDGFR inhibitor JNJ-10198409 (JNJ) and the IGF-1R inhibitor picropodophyllin
      (PPP) in glioblastoma cell lines as well as in primary cultures derived from
      patients affected by this type of tumor. JNJ and PPP treatment blocked PDGFR and
      IGF-1R signaling respectively and reduced Akt and Erk 1/2 phosphorylation. Both
      inhibitors diminished cell proliferation, inducing a G2/M block of the cell
      cycle. Cell death induced by JNJ was caspase-dependent, Annexin-V positive and
      caused PARP cleavage, especially in T98 cells, suggesting an apoptotic mechanism.
      However, cell death induced by PPP was not completely inhibited by caspase
      inhibitors in all cell lines apart from LN-229 cells, indicating a caspase
      independent mechanism. Several inhibitors targeted against different cell death
      pathways could not block this caspase-independent component, which may be a non
      programmed necrotic mechanism. Apoptotic arrays performed in T98 and LN-229 cells
      upon JNJ and PPP treatment revealed that procaspase 3 levels were augmented by
      both drugs in T98 cells and only by JNJ in LN229-cells. Furthermore, XIAP and
      survivin levels were much higher in LN-229 cells than in T98 cells, revealing
      that LN-229 cells are more susceptible to undergo caspase-independent cell death
      mechanisms. JNJ and PPP combination was more effective than each treatment alone.

PMID- 30200645
TI  - Paralytic Shellfish Toxins Occurrence in Non-Traditional Invertebrate Vectors
      from North Atlantic Waters (Azores, Madeira, and Morocco).
AB  - Paralytic shellfish toxins (PSTs) are potent alkaloids of microalgal and
      cyanobacterial origin, with worldwide distribution. Over the last 20 years, the
      number of poisoning incidents has declined as a result of the implementation of
      legislation and monitoring programs based on bivalves. In the summer of 2012 and
      2013, we collected a total of 98 samples from 23 different species belonging to
      benthic and subtidal organisms, such as echinoderms, crustaceans, bivalves, and
      gastropods. The sampling locations were Madeira, Sao Miguel Island (Azores
      archipelago), and the northwestern coast of Morocco. The samples were analyzed
      using post-column oxidation liquid chromatography with a fluorescence detection
      method. Our main goal was to detect new vectors for these biotoxins. After
      reporting a total of 59 positive results for PSTs with 14 new vectors identified,
      we verified that some of the amounts exceeded the limit value established in the
      EU. These results suggest that routine monitoring of saxitoxin and its analogs
      should be extended to more potential vectors other than bivalves, including other
      edible organisms, for a better protection of public health.

PMID- 30200647
TI  - Phase Formation during Solidification of Mg-Nd-Zn Alloys: An In Situ Synchrotron
      Radiation Diffraction Study.
AB  - Mg-4Nd base alloys with Zn additions of 3, 5 and 8 wt % were investigated with in
      situ synchrotron radiation diffraction during solidification. This method enabled
      the investigation of phase formation and transformation in the alloys. The
      diffraction results were supported with TEM observations on the as-solidified
      samples. The results show the effect of increased Zn addition on stabilizing the
      Mg3RE phase (RE-rare earth). The experimental results agree only partially with
      the theoretical calculations indicating the need to improve the existing
      thermodynamic database on the alloy system.

PMID- 30200646
TI  - Coexistence of TERT Promoter Mutations and the BRAF V600E Alteration and Its
      Impact on Histopathological Features of Papillary Thyroid Carcinoma in a Selected
      Series of Polish Patients.
AB  - TERT promoter (TERTp) mutations are important factors in papillary thyroid
      carcinomas (PTCs). They are associated with tumor aggressiveness, recurrence, and
      disease-specific mortality and their use in risk stratification of PTC patients
      has been proposed. In this study we investigated the prevalence of TERTp
      mutations in a cohort of Polish patients with PTCs and the association of these
      mutations with histopathological factors, particularly in coexistence with the
      BRAF V600E mutation. A total of 189 consecutive PTC specimens with known BRAF
      mutational status were evaluated. TERTp mutations were detected in 8.5% of cases
      (16/189) with the C228T mutation being the most frequent. In six of the PTC
      specimens (3.2%), four additional TERTp alterations were found, which included
      one known polymorphism (rs2735943) and three previously unreported alterations.
      The association analysis revealed that the TERTp hotspot mutations were highly
      correlated with the presence of the BRAF V600E mutation and their coexistence was
      significantly associated with gender, advanced patient age, advanced disease
      stage, presence of lymph node metastases, larger tumor size, and tumor-capsule
      infiltration. While correlations were identified, the possibility of TERTp
      mutations being key molecular modulators responsible for PTC aggressiveness
      requires further studies.

PMID- 30200648
TI  - Dy(III) Doped BiOCl Powder with Superior Highly Visible-Light-Driven
      Photocatalytic Activity for Rhodamine B Photodegradation.
AB  - Dy-doped BiOCl powder photocatalyst was synthesized A one-step coprecipitation
      method. The incorporation of Dy3+ replaced partial Bi3+ in BiOCl crystal lattice
      system. For Rhodamine B (RhB) under visible light irradiation, 2% Dy doped BiOCl
      possessed highly efficient photocatalytic activity and photodegradation
      efficiency. The photodegradation ratio of RhB could reach 97.3% after only 30 min
      of photocatalytic reaction; this was more than relative investigations have
      reported in the last two years. The main reason was that the 4f electron shell of
      Dy in the BiOCl crystal lattice system can generate a special electronic shell
      structure that facilitated the transfer of electron from valance band to
      conduction band and separation of the photoinduced charge carrier. Apart from
      material preparation, this research is expected to provide important references
      for RhB photodegradation in practical applications.

PMID- 30200649
TI  - A Novel Surface Acoustic Wave Sensor Array Based on Wireless Communication
      Network.
AB  - A novel surface acoustic wave (SAW) sensor array based on wireless communication
      network is prepared. The array is composed of four SAW sensors, a wireless
      communication network module, and a global positioning system (GPS) module. The
      four SAW sensors of the array are coated with triethanolamine,
      polyepichlorohydrin, fluoroalcoholpolysiloxane, and L-glutamic acid hydrochloride
      to detect hydrogen sulfide (H2S), 2-chloroethyl ethyl sulfide (CEES),
      dimethylmethylphosphonate (DMMP), and ammonia (NH3) at film thicknesses of 50-100
      nm. The wireless communication network module consists of an acquisition unit, a
      wireless control unit, and a microcontroller unit. By means of Zigbee and Lora
      technologies, the module receives and transmits the collected data to a PC work
      station in real-time; moreover, the module can control the sensor array's working
      mode and monitor the working status. Simultaneously, the testing location is
      determined by the GPS module integrated into the SAW sensor array. H2S, CEES,
      DMMP, and NH3 are detected in 300 m at different concentrations. Given the
      practical future application in environment in the future, the low, safe
      concentrations of 1.08, 0.59, 0.10, and 5.02 ppm for H2S, CEES, DMMP, and NH3,
      respectively, are detected at the lowest concentration, and the sensitivities of
      different sensors of the sensor array are 32.4, 14.9, 78.1 and 22.6 Hz/ppm,
      respectively. With the obtained fingerprints and pattern recognition technology,
      the detected gases can be recognized.

PMID- 30200650
TI  - Comparison of Flank Super Abrasive Machining vs. Flank Milling on Inconel(r) 718
      Surfaces.
AB  - Thermoresistant superalloys present many challenges in terms of machinability,
      which leads to finding new alternatives to conventional manufacturing processes.
      In order to face this issue, super abrasive machining (SAM) is presented as a
      solution due to the fact that it combines the advantages of the use of grinding
      tools with milling feed rates. This technique is commonly used for finishing
      operations. Nevertheless, this work analyses the feasibility of this technique
      for roughing operations. In order to verify the adequacy of this new technique as
      an alternative to conventional process for roughing operations, five slots were
      performed in Inconel(r) 718 using flank SAM and flank milling. The results showed
      that flank SAM implies a suitable and controllable process to improve the
      manufacture of high added value components made by nickel-based superalloys in
      terms of roughness, microhardness, white layer, and residual stresses.

PMID- 30200651
TI  - Real-Time Safety Evaluation for Slope during Construction Using Numerical
      Forecast and Sensor Monitoring Platform.
AB  - Geology uncertainties and real-time construction modification induce an increase
      of construction risk for large-scale slope in hydraulic engineering. However, the
      real-time evaluation of slope safety during construction is still an unsettled
      issue for mapping large-scale slope hazards. In this study, the real-time safety
      evaluation method is proposed coupling a construction progress with numerical
      analysis of slope safety. New revealed geological information, excavation
      progress adjustment, and the support structures modification are updating into
      the slope safety information model-by-model restructuring. A dynamic connection
      mapping method between the slope restructuring model and the computable numerical
      model is illustrated. The numerical model can be generated rapidly and
      automatically in database. A real-time slope safety evaluation system is
      developed and its establishing method, prominent features, and application
      results are briefly introduced in this paper. In our system, the interpretation
      of potential slope risk is conducted coupling dynamic numerical forecast and
      monitoring data feedback. The real case study results in a comprehensive real
      time safety evaluation application for large slope that illustrates the change of
      environmental factor and construction state over time.

PMID- 30200652
TI  - Modeling the Human Visuo-Motor System to Support Remote-Control Operation.
AB  - The working hypothesis in this project is that gaze interactions play a central
      role in structuring the joint control and guidance strategy of the human operator
      performing spatial tasks. Perceptual guidance and control is the idea that the
      visual and motor systems form a unified perceptuo-motor system where necessary
      information is naturally extracted by the visual system. As a consequence, the
      response of this system is constrained by the visual and motor mechanisms and
      these effects should manifest in the behavioral data. Modeling the perceptual
      processes of the human operator provides the foundation necessary for a systems
      based approach to the design of control and display systems used by remotely
      operated vehicles. This paper investigates this hypothesis using flight tasks
      conducted with remotely controlled miniature rotorcraft, taking place in indoor
      settings that provide rich environments to investigate the key processes
      supporting spatial interactions. This work also applies to spatial control tasks
      in a range of application domains that include tele-operation, gaming, and
      virtual reality. The human-in-the-loop system combines the dynamics of the
      vehicle, environment, and human perception-action with the response of the
      overall system emerging from the interplay of perception and action. The main
      questions to be answered in this work are as follows: (i) what is the general
      control and guidance strategy of the human operator, and (ii) how is information
      about the vehicle and environment extracted visually by the operator. The general
      approach uses gaze as the primary sensory mechanism by decoding the gaze patterns
      of the pilot to provide information for estimation, control, and guidance. This
      work differs from existing research by taking what have largely been conceptual
      ideas on action-perception and structuring them to be implemented for a real
      world problem. The paper proposes a system model that captures the human pilot's
      perception-action loop; the loop that delineates the main components of the
      pilot's perceptuo-motor system, including estimation of the vehicle state and
      task elements based on operator gaze patterns, trajectory planning, and tracking
      control. The identified human visuo-motor model is then exploited to demonstrate
      how the perceptual and control functions system can be augmented to reduce the
      operator workload.

PMID- 30200653
TI  - Pumpkin CmHKT1;1 Controls Shoot Na+ Accumulation via Limiting Na+ Transport from
      Rootstock to Scion in Grafted Cucumber.
AB  - Soil salinity adversely affects the growth and yield of crops, including
      cucumber, one of the most important vegetables in the world. Grafting with salt
      tolerant pumpkin as the rootstock effectively improves the growth of cucumber
      under different salt conditions by limiting Na+ transport from the pumpkin
      rootstock to the cucumber scion. High-affinity potassium transporters (HKTs) are
      crucial for the long distance transport of Na+ in plants, but the function of
      pumpkin HKTs in this process of grafted cucumber plants remains unclear. In this
      work, we have characterized CmHKT1;1 as a member of the HKT gene family in
      Cucurbita moschata and observed an obvious upregulation of CmHKT1;1 in roots
      under NaCl stress conditions. Heterologous expression analyses in yeast mutants
      indicated that CmHKT1;1 is a Na+-selective transporter. The transient expression
      in tobacco epidermal cells and in situ hybridization showed CmHKT1;1 localization
      at plasma membrane, and preferential expression in root stele. Moreover, ectopic
      expression of CmHKT1;1 in cucumber decreased the Na+ accumulation in the plants
      shoots. Finally, the CmHKT1;1 transgenic line as the rootstock decreased the Na+
      content in the wild type shoots. These findings suggest that CmHKT1;1 plays a key
      role in the salt tolerance of grafted cucumber by limiting Na+ transport from the
      rootstock to the scion and can further be useful for engineering salt tolerance
      in cucurbit crops.

PMID- 30200654
TI  - "Holes" in the Jaw-A Report of Two Cases of Periapical Actinomycosis.
AB  - Periapical actinomycosis is a relatively rare form of cervicofacial
      actinomycosis, which typically involves the periapical region with subsequent
      potential spread to the jaw bones. We hereby present two cases of periapical
      actinomycosis. Both patients presented with jaw pain and "holes" in their gum and
      lacked the characteristic clinical features commonly seen in cervicofacial
      actinomycosis such as jaw mass, draining ulcers, sinuses and fistulae. The first
      patient was an immunocompetent host with chronic stable medical conditions but
      with a rather bad dentition requiring multiple recent teeth extractions. The
      second patient was edentulous, had refractory multiple myeloma, was on low-dose
      chronic steroids and pomalidomide therapy and therefore relatively
      immunocompromised. Both cases of actinomycosis were diagnosed by jaw bone
      histopathology, which showed characteristic sulfur granules and embedded
      Actinomyces-like organisms. The two patients had excellent clinical response to
      six months of penicillin therapy without any need for surgical intervention. The
      cases remind clinicians of including actinomycosis in the differential diagnosis
      of periapical lesions and illustrates the possibility of achieving cure with non
      surgical treatment.

PMID- 30200656
TI  - Development of CdSe-ZnO Flower-Rod Core-Shell Structure Based
      Photoelectrochemical Biosensor for Detection of Norovirous RNA.
AB  - In this work, the CdSe-ZnO flower-rod core-shell structure (CSZFRs) was prepared
      by ion-exchange method. The surface of CSZFRs was modified by 3-mercaptopropionic
      acid (MPA), and then the DNA probe was immobilized on the surface via chemical
      bond between -NH2 of DNA probe and -COOH of MPA. Finally, the target norovirous
      (NV) RNA was combined with the probe according to the principle of complementary
      base pairing, resulting in a decrease of the photocurrent. The results show that
      the absorbance spectrum of visible light is enhanced for CSZFRs compared with
      pure ZnO. Under visible light irradiation, the photocurrent of CSZFRs is up to
      0.1 mA, which can improve the sensitivity of the photoelectrochemical (PEC)
      biosensor. In the measurement range of 0-5.10 nM, the measured concentrations (c)
      have a good linear relationship with the output photocurrent of the biosensor.
      The linear regression equation is expressed as I = 0.03256 - 0.0033c (R2 = 0.99,
      S/N = 3) with a detection limit of 0.50 nM. Therefore, this work realizes a rapid
      and sensitive method for the detection of NV RNA.

PMID- 30200657
TI  - Sol-Gel Immobilisation of Lipases: Towards Active and Stable Biocatalysts for the
      Esterification of Valeric Acid.
AB  - Alkyl esters are high added value products useful in a wide range of industrial
      sectors. A methodology based on a simple sol-gel approach (biosilicification) is
      herein proposed to encapsulate enzymes in order to design highly active and
      stable biocatalysts. Their performance was assessed through the optimization of
      valeric acid esterification evaluating the effect of different parameters
      (biocatalyst load, presence of water, reaction temperature and stirring rate) in
      different alcoholic media, and comparing two different methodologies:
      conventional heating and microwave irradiation. Ethyl valerate yields were in the
      80-85% range under optimum conditions (15 min, 12% m/v biocatalyst, molar ratio
      1:2 of valeric acid to alcohol). Comparatively, the biocatalysts were slightly
      deactivated under microwave irradiation due to enzyme denaturalisation.
      Biocatalyst reuse was attempted to prove that good reusability of these sol-gel
      immobilised enzymes could be achieved under conventional heating.

PMID- 30200655
TI  - Prospective Associations of Erythrocyte Composition and Dietary Intake of n-3 and
      n-6 PUFA with Measures of Cognitive Function.
AB  - Polyunsaturated fatty acid (PUFA) consumption is recommended as part of a healthy
      diet, but evidence of the impact of individual species and biological
      concentrations on cognitive function is limited. We examined prospective
      associations of PUFA erythrocyte composition and dietary intake with measures of
      cognitive function among participants of the Boston Puerto Rican Health Study
      (aged 57 years). Erythrocyte and dietary PUFA composition were ascertained at
      baseline and associated with 2-year scores on the Mini-Mental State Exam (MMSE)
      (n = 1032) and cognitive domain patterns derived from a battery of tests (n =
      865), as well as with incidence of cognitive impairment. Erythrocyte and dietary
      n-3 PUFA were not significantly associated with MMSE score. However, total
      erythrocyte and dietary n-3 very-long-chain fatty acids (VLCFA), and intake of
      individual species, were associated with better executive function (P-trend <
      0.05, for all). There was evidence that greater erythrocyte n-6 eicosadienoic
      acid concentration was associated with lower MMSE and executive function scores
      (P-trend = 0.02). Only erythrocyte arachidonic acid (ARA) concentration predicted
      cognitive impairment (Odds Ratio = 1.26; P = 0.01). Among Puerto Rican adults, we
      found that n-3 VLCFA consumption may beneficially impact executive function.
      Further, these findings provide some evidence that n-6 metabolism favoring
      greater ARA tissue incorporation, but not necessarily dietary intake, could
      increase the risk of cognitive impairment.

PMID- 30200658
TI  - Bioinformatics Analysis of SNPs in IL-6 Gene Promoter of Jinghai Yellow Chickens.
AB  - The proinflammatory cytokine, interleukin-6 (IL-6), plays a critical role in many
      chronic inflammatory diseases, particularly inflammatory bowel disease. To
      investigate the regulation of IL-6 gene expression at the molecular level,
      genomic DNA sequencing of Jinghai yellow chickens (Gallus gallus) was performed
      to detect single-nucleotide polymorphisms (SNPs) in the region -2200 base pairs
      (bp) upstream to 500 bp downstream of IL-6. Transcription factor binding sites
      and CpG islands in the IL-6 promoter region were predicted using bioinformatics
      software. Twenty-eight SNP sites were identified in IL-6. Four of these 28 SNPs,
      three [-357 (G > A), -447 (C > G), and -663 (A > G)] in the 5' regulatory region
      and one in the 3' non-coding region [3177 (C > T)] are not labelled in GenBank.
      Bioinformatics analysis revealed 11 SNPs within the promoter region that altered
      putative transcription factor binding sites. Furthermore, the C-939G mutation in
      the promoter region may change the number of CpG islands, and SNPs in the 5'
      regulatory region may influence IL-6 gene expression by altering transcription
      factor binding or CpG methylation status. Genetic diversity analysis revealed
      that the newly discovered A-663G site significantly deviated from Hardy-Weinberg
      equilibrium. These results provide a basis for further exploration of the
      promoter function of the IL-6 gene and the relationships of these SNPs to
      intestinal inflammation resistance in chickens.

PMID- 30200659
TI  - Changes in Plasma Acylcarnitine and Lysophosphatidylcholine Levels Following a
      High-Fructose Diet: A Targeted Metabolomics Study in Healthy Women.
AB  - BACKGROUND: The consumption of high amounts of fructose is associated with
      metabolic diseases. However, the underlying mechanisms are largely unknown.
      OBJECTIVE: To determine the effects of high fructose intake on plasma
      metabolomics. STUDY DESIGN: We enrolled 12 healthy volunteers (six lean and six
      obese women, age 24-35 years) in a crossover intervention study. All participants
      carried out three diets: (1) low fructose (<10 g/day); (2) high fructose (100
      g/day) from natural food sources (fruit); and (3) high fructose (100 g/day) from
      high fructose syrup (HFS). OUTCOME MEASURES: The primary outcome was changes in
      plasma metabolites measured by targeted metabolomics. RESULTS: High compared to
      low fructose diets caused a marked metabolite class separation, especially
      because of changes in acylcarnitine and lysophosphatidylcholine levels. Both high
      fructose diets resulted in a decrease in mean acylcarnitine levels in all
      subjects, and an increase in mean lysophosphatidylcholine and diacyl
      phosphatidylcholine levels in obese individuals. Medium chain acylcarnitines were
      negatively correlated with serum levels of liver enzymes and with the fatty liver
      index. DISCUSSION: The metabolic shifts induced by high fructose consumption
      suggest an inhibition of mitochondrial beta-oxidation and an increase in lipid
      peroxidation. The effects tended to be more pronounced following the HFS than the
      fruit diet.

PMID- 30200660
TI  - Mechanism of Lakoochin A Inducing Apoptosis of A375.S2 Melanoma Cells through
      Mitochondrial ROS and MAPKs Pathway.
AB  - Malignant melanoma is developed from pigment-containing cells, melanocytes, and
      primarily found on the skin. Malignant melanoma still has a high mortality rate,
      which may imply a lack of therapeutic agents. Lakoochin A, a compound isolated
      from Artocarpus lakoocha and Artocarpus xanthocarpus, has an inhibitory function
      of tyrosinase activity and melanin production, but the anti-cancer effects are
      still unclear. In the current study, the therapeutic effects of lakoochin A with
      their apoptosis functions and possible mechanisms were investigated on A375.S2
      melanoma cells. Several methods were applied, including 3-(4,5-Dimethylthiazol-2
      yl)-2,5- diphenyltetrazolium bromide (MTT), flow cytometry, and immunoblotting.
      Results suggest that lakoochin A attenuated the growth of A375.S2 melanoma cells
      through an apoptosis mechanism. Lakoochin A first increase the production of
      cellular and mitochondrial reactive oxygen species (ROSs); mitochondrial ROSs
      then promote mitogen-activated protein kinases (MAPKs) pathway activation and
      raise downstream apoptosis-related protein and caspase expression. This is the
      first study to demonstrate that lakoochin A, through ROS-MAPK, apoptosis-related
      proteins, caspases cascades, can induce melanoma cell apoptosis and may be a
      potential candidate compound for treating malignant melanoma.

PMID- 30200661
TI  - Associations among Elder Abuse, Depression and PTSD in South Korean Older Adults.
AB  - Increasing attention is being placed on the prevalence of elder abuse and its
      impact on mental health. This study conducted a survey of 172 elderly people in
      South Korea to determine the prevalence of elder abuse and the relationships
      involving elder abuse, depression and posttraumatic stress disorder (PTSD).
      Participants completed a battery of self-report questionnaires, which included
      the Korean Geriatric Depression Screening Scale (KGDS) and Impact of Event Scale
      Revised Korean version (IES-R-K). Descriptive analyses were conducted to examine
      the frequency of specific forms of abuse. Logistic regression models were
      estimated to identify the factors that contributed to risk of abuse exposure and
      the relationship between exposure and PTSD or depression. The results indicated
      around 22% of the participants reported abuse exposure, which most commonly
      included being refused physical contact, verbal threats, and/or being excluded
      from decision-making about personal issues. Low education and being unmarried,
      separated or divorced was associated with an increased risk of abuse exposure.
      There were strong associations between elder abuse and PTSD symptoms, while
      comparable relationships with depression were weaker and were not robust to the
      inclusion of control variables. The findings provided empirical support for the
      relationship between abuse experiences of the elderly and poor mental health and
      raise important issues for the mental health care of the elderly.

PMID- 30200663
TI  - Effects of Pore Size on Fatigue Deformation Mechanism of Open-Cell Copper Foam at
      Low Stress Amplitude.
AB  - Axial compression-compression fatigue experiments on open-cell copper foams with
      different pore size were investigated in this paper. The effects of the strain
      amplitude on the fatigue properties were studied and found that there is an
      exponential relationship between the fatigue life and strain amplitude. The
      experimental results indicate that a smaller pore size is related to a lower
      fatigue life. The microstructures of failed copper foam tested at low stress
      amplitude were observed by optical microscope and scanning electron microscopy
      (SEM), suggests that different pore size related to different fatigue behavior.
      The fatigue failure mechanism of the open-cell copper foams were compared by
      experimental research.

PMID- 30200662
TI  - Identification of Putative Novel Class-I Lanthipeptides in Firmicutes: A
      Combinatorial In Silico Analysis Approach Performed on Genome Sequenced Bacteria
      and a Close Inspection of Z-Geobacillin Lanthipeptide Biosynthesis Gene Cluster
      of the Thermophilic Geobacillus sp. Strain ZGt-1.
AB  - Lanthipeptides are ribosomally synthesized and post-translationally modified
      polycyclic peptides. Lanthipeptides that have antimicrobial activity are known as
      lantibiotics. Accordingly, the discovery of novel lantibiotics constitutes a
      possible solution for the problem of antibiotic resistance. We utilized the
      publicly available genome sequences and the bioinformatic tools tailored for the
      detection of lanthipeptides. We designed our strategy for screening of 252
      firmicute genomes and detecting class-I lanthipeptide-coding gene clusters. The
      designed strategy resulted in identifying 69 class-I lanthipeptide sequences, of
      which more than 10% were putative novel. The identified putative novel
      lanthipeptides have not been annotated on the original or the RefSeq genomes, or
      have been annotated merely as coding for hypothetical proteins. Additionally, we
      identified bacterial strains that have not been previously recognized as
      lanthipeptide-producers. Moreover, we suggest corrections for certain firmicute
      genome annotations, and recommend lanthipeptide records for enriching the
      bacteriocin genome mining tool (BAGEL) databases. Furthermore, we propose Z
      geobacillin, a putative class-I lanthipeptide coded on the genome of the
      thermophilic strain Geobacillus sp. ZGt-1. We provide lists of putative novel
      lanthipeptide sequences and of the previously unrecognized lanthipeptide
      producing bacterial strains, so they can be prioritized for experimental
      investigation. Our results are expected to benefit researchers interested in the
      in vitro production of lanthipeptides.

PMID- 30200665
TI  - Structured-Light Based 3D Reconstruction System for Cultural Relic Packaging.
AB  - The non-contact three-dimensional measurement and reconstruction techniques have
      played a significant role in the packaging and transportation of precious
      cultural relics. This paper develops a structured light based three-dimensional
      measurement system, with a low-cost for cultural relics packaging. The structured
      light based system performs rapid measurements and generates 3D point cloud data,
      which is then denoised, registered and merged to achieve accurate 3D
      reconstruction for cultural relics. The multi-frequency heterodyne method and the
      method in this paper are compared. It is shown that the relative accuracy of the
      proposed low-cost system can reach a level of 1/1000. The high efficiency of the
      system is demonstrated through experimental results.

PMID- 30200664
TI  - Marine Microalgae: Promising Source for New Bioactive Compounds.
AB  - The study of marine natural products for their bioactive potential has gained
      strength in recent years. Oceans harbor a vast variety of organisms that offer a
      biological and chemical diversity with metabolic abilities unrivalled in
      terrestrial systems, which makes them an attractive target for bioprospecting as
      an almost untapped resource of biotechnological applications. Among them, there
      is no doubt that microalgae could become genuine "cell factories" for the
      biological synthesis of bioactive substances. Thus, in the course of inter
      laboratory collaboration sponsored by the European Union (7th FP) into the MAREX
      Project focused on the discovery of novel bioactive compounds of marine origin
      for the European industry, a bioprospecting study on 33 microalgae strains was
      carried out. The strains were cultured at laboratory scale. Two extracts were
      prepared for each one (biomass and cell free culture medium) and, thus, screened
      to provide information on the antimicrobial, the anti-proliferative, and the
      apoptotic potential of the studied extracts. The outcome of this study provides
      additional scientific data for the selection of Alexadrium tamarensis WE,
      Gambierdiscus australes, Prorocentrum arenarium, Prorocentrum hoffmannianum, and
      Prorocentrum reticulatum (Pr-3) for further investigation and offers support for
      the continued research of new potential drugs for human therapeutics from
      cultured microalgae.

PMID- 30200667
TI  - Ecohydraulogical Characteristic Index System of Schizopygopsis younghusbandi
      during Spawning Periods in the Yarlung Tsangpo River.
AB  - To address the species decline in aboriginal fish in the Yarlung Tsangpo River
      Basin and the lack of research on the habitat characteristics of fish spawning
      grounds, this paper studied the changing trends in runoff in spawning grounds and
      the habitat conditions characteristics of Schizopygopsis younghusbandi during the
      spawning period. In conventional approaches, inaccurate statistical results are
      obtained when a full river section is taken as the region to be assessed, so a
      new method for determining the statistical boundaries of characteristic indexes
      was proposed. By combining hydrological analyses, mathematical statistics, and
      numerical simulations, the statistical boundary of the index was determined, and
      a suitable range for the habitat characteristic indexes for the spawning field
      was finally obtained. The results showed that (1) the maximum percentage of the
      statistical boundary for the spawning grounds was 39% near the banks on both
      sides of the river; (2) the flow during the spawning period exhibited small
      variations, a short duration and a fluctuation cycle and was dominated by water
      rising events, and the interannual growth trend in the daily flow was obvious;
      and (3) during the spawning period, the flow velocity of the fish habitat was
      small, the turbulence level of the fluid was low, and the flow regime was stable.
      A suitable range for the habitat characteristic index of the target fish provided
      the basic data for the protection of aboriginal fish and was beneficial to
      maintain the balance of aquatic ecological system in the Yarlung Tsangpo River.
      The results of this study contribute to the rational development of water
      resources in the basin and the protection of species diversity and water
      environment.

PMID- 30200666
TI  - The Extracellular Matrix and Pancreatic Cancer: A Complex Relationship.
AB  - Pancreatic ductal adenocarcinoma (PDAC) has an extraordinarily dense fibrotic
      stroma that impedes tumor perfusion and delivery of anticancer drugs. Since the
      extracellular matrix (ECM) comprises the bulk of the stroma, it is primarily
      responsible for the increased interstitial tissue pressure and stiff mechanical
      properties of the stroma. Besides its mechanical influence, the ECM provides
      important biochemical and physical cues that promote survival, proliferation, and
      metastasis. By serving as a nutritional source, the ECM also enables PDAC cells
      to survive under the nutrient-poor conditions. While therapeutic strategies using
      stroma-depleting drugs have yielded disappointing results, an increasing body of
      research indicates the ECM may offer a variety of potential therapeutic targets.
      As preclinical studies of ECM-targeted drugs have shown promising effects, a
      number of clinical trials are currently investigating agents with the potential
      to advance the future treatment of PDAC. Thus, the present review seeks to give
      an overview of the complex relationship between the ECM and PDAC.

PMID- 30200669
TI  - Lactobacillus acidophilus DDS-1 Modulates the Gut Microbiota and Improves
      Metabolic Profiles in Aging Mice.
AB  - Recent evidence suggests that gut microbiota shifts can alter host metabolism
      even during healthy aging. Lactobacillus acidophilus DDS-1, a probiotic strain,
      has shown promising probiotic character in vitro, as well as in clinical studies.
      The present study was carried out to investigate whether DDS-1 can modulate the
      host metabolic phenotype under the condition of age-affected gut microbial shifts
      in young and aging C57BL/6J mice. Collected fecal samples were analyzed using 16S
      rRNA gene sequencing for identifying gut microbiota and untargeted gas
      chromatography-mass spectrometry (GC-MS) metabolomics analysis. Gut microbial
      shifts were observed in the control groups (young and aging), leading to an
      alteration in metabolism. Principal coordinate analysis (PCoA) of microbiota
      indicated distinct separation in both the DDS-1-treated groups. L. acidophilus
      DDS-1 increased the relative abundances of beneficial bacteria, such as
      Akkermansia muciniphila and Lactobacillus spp., and reduced the relative levels
      of opportunistic bacteria such as Proteobacteria spp. Metabolic pathway analysis
      identified 10 key pathways involving amino acid metabolism, protein synthesis and
      metabolism, carbohydrate metabolism, and butanoate metabolism. These findings
      suggest that modulation of gut microbiota by DDS-1 results in improvement of
      metabolic phenotype in the aging mice.

PMID- 30200670
TI  - Topical Plant Polyphenols Prevent Type I Interferon Signaling in the Skin and
      Suppress Contact Hypersensitivity.
AB  - Human keratinocytes were recently shown to respond to anti-EGFR (epidermal growth
      factor receptor) drugs with activation of an interferon-kappa-driven autocrine
      loop, leading to enhanced expression of innate antiviral effectors and of the pro
      inflammatory chemokines CXCL10 (C-X-C motif chemokine 10) and CCL2 (C-C motif
      ligand 2). Here we showed active type I interferon signaling in the skin lesions
      of cancer patients undergoing treatment with the anti-EGFR drug cetuximab. Strong
      nuclear positivity for Interferon Regulatory Factor 1 and phosphorylated Signal
      Transducer and Activator of Transcription 1, enhanced interferon-kappa expression
      and CXCL10 was associated to the epidermal compartment. Notably, 50 micromolar
      resveratrol and quercetin fully suppressed the low constitutive levels of type I
      interferon signaling and prevented its activation by the anti-EGFR cetuximab or
      gefitinib in cultured keratinocytes. In sensitized mice undergoing DNFB (2,4
      dinitro-1-fluorobenzene)-induced contact hypersensitivity, local administration
      of gefitinib prior to elicitation further amplified hapten-induced type I
      interferon activation, tissue edema, and infiltration by T cells, whereas
      resveratrol or quercetin suppressed this inflammatory cascade. Overall, these
      data suggest that topical application of resveratrol or quercetin could be
      potentially effective in preventing pathological conditions due to overactivation
      of type I IFN (interferon)-driven circuits in the skin, including the
      inflammatory manifestations of anti-EGFR drug-induced skin-targeted toxicity.

PMID- 30200671
TI  - Temporal Trends of Urinary Phthalate Concentrations in Two Populations: Effects
      of REACH Authorization after Five Years.
AB  - Phthalates are widely used in the industrial manufacture of many products. Some
      phthalates have shown reproductive toxicity in humans, acting as endocrine
      disruptors, so they were included in the authorization process defined in Reg. CE
      1907/2006 (REACH). Two groups of population were recruited, before and after the
      inclusion of some phthalates in the authorization list in REACH: the first group
      of 157 volunteers was studied in 2011 and the second, 171 volunteers, in 2016.
      Each subject completed a questionnaire about personal lifestyle, working
      activities and use of chemical products. The main urinary metabolites of five
      phthalates were analyzed by HPLC/MS/MS: mono(2-ethylhexyl)phthalate (MEHP) and
      mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) for di(2-ethylhexyl)phthalate
      (DEHP) exposure; monoethylphthalate (MEP) for diethylphtahate (DEP);
      monobenzylphthalate (MBzP) for butylbenzylphtahalate (BBP) and dibenzylphthalate
      (DBzP), mono-n-butylphthalate (MnBP) for butylbenzylphtahalate (BBP) and di-n
      butylphthalate (DnBP). The results show a significant difference for all
      metabolites between the two periods, with the exception of MEP in women. The
      comparison of the two sets of results shows a decrease in urinary metabolites
      excretion from 2011 to 2016, statistically significant for the three phthalates
      included in Annex XIV of REACH. DEP, not currently included in the list for
      authorization, maintains a constant presence in the daily life of the population,
      particularly for women.

PMID- 30200672
TI  - Implementation of Spiegler-Kedem and Steric Hindrance Pore Models for Analyzing
      Nanofiltration Membrane Performance for Smart Water Production.
AB  - A predictive model correlating the parameters in the mass transfer-based model
      Spiegler-Kedem to the pure water permeability is presented in this research,
      which helps to select porous polyamide membranes for enhanced oil recovery (EOR)
      applications. Using the experimentally obtained values of flux and rejection, the
      reflection coefficient sigma and solute permeability Ps have been estimated as
      the mass transfer-based model parameters for individual ions in seawater. The
      reflection coefficient and solute permeability determined were correlated with
      the pure water permeability of a membrane, which is related to the structural
      parameters of a membrane. The novelty of this research is the development of a
      model that consolidates the various complex mechanisms in the mass transfer of
      ions through the membrane to an empirical correlation for a given feed
      concentration and membrane type. These correlations were later used to predict
      ion rejections of any polyamide membrane with a known pure water permeability and
      flux with seawater as a feed that aids in the selection of suitable
      nanofiltration (NF) for smart water production.

PMID- 30200668
TI  - Structure-Based Classification and Anti-Cancer Effects of Plant Metabolites.
AB  - A variety of malignant cancers affect the global human population. Although a
      wide variety of approaches to cancer treatment have been studied and used
      clinically (surgery, radiotherapy, chemotherapy, and immunotherapy), the toxic
      side effects of cancer therapies have a negative impact on patients and impede
      progress in conquering cancer. Plant metabolites are emerging as new leads for
      anti-cancer drug development. This review summarizes these plant metabolites with
      regard to their structures and the types of cancer against which they show
      activity, organized by the organ or tissues in which each cancer forms. This
      information will be helpful for understanding the current state of knowledge of
      the anti-cancer effects of various plant metabolites against major types of
      cancer for the further development of novel anti-cancer drugs.

PMID- 30200675
TI  - Dynamic Computation Offloading Scheme for Drone-Based Surveillance Systems.
AB  - Recently, various technologies for utilizing unmanned aerial vehicles have been
      studied. Drones are a kind of unmanned aerial vehicle. Drone-based mobile
      surveillance systems can be applied for various purposes such as object
      recognition or object tracking. In this paper, we propose a mobility-aware
      dynamic computation offloading scheme, which can be used for tracking and
      recognizing a moving object on the drone. The purpose of the proposed scheme is
      to reduce the time required for recognizing and tracking a moving target object.
      Reducing recognition and tracking time is a very important issue because it is a
      very time critical job. Our dynamic computation offloading scheme considers both
      the dwell time of the moving target object and the network failure rate to
      estimate the response time accurately. Based on the simulation results, our
      dynamic computation offloading scheme can reduce the response time required for
      tracking the moving target object efficiently.

PMID- 30200673
TI  - Infectious Bronchitis Virus Nonstructural Protein 4 Alone Induces Membrane
      Pairing.
AB  - Positive-strand RNA viruses, such as coronaviruses, induce cellular membrane
      rearrangements during replication to form replication organelles allowing for
      efficient viral RNA synthesis. Infectious bronchitis virus (IBV), a pathogenic
      avian Gammacoronavirus of significant importance to the global poultry industry,
      has been shown to induce the formation of double membrane vesicles (DMVs),
      zippered endoplasmic reticulum (zER) and tethered vesicles, known as spherules.
      These membrane rearrangements are virally induced; however, it remains unclear
      which viral proteins are responsible. In this study, membrane rearrangements
      induced when expressing viral non-structural proteins (nsps) from two different
      strains of IBV were compared. Three non-structural transmembrane proteins, nsp3,
      nsp4, and nsp6, were expressed in cells singularly or in combination and the
      effects on cellular membranes investigated using electron microscopy and electron
      tomography. In contrast to previously studied coronaviruses, IBV nsp4 alone is
      necessary and sufficient to induce membrane pairing; however, expression of the
      transmembrane proteins together was not sufficient to fully recapitulate DMVs.
      This indicates that although nsp4 is able to singularly induce membrane pairing,
      further viral or host factors are required in order to fully assemble IBV
      replicative structures. This study highlights further differences in the
      mechanism of membrane rearrangements between members of the coronavirus family.

PMID- 30200674
TI  - The Inhibitory Effect of Ojeoksan on Early and Advanced Atherosclerosis.
AB  - Atherosclerosis is closely related to vascular dysfunction and hypertension.
      Ojeoksan (OJS), originally recorded in an ancient Korean medicinal book named
      "Donguibogam", is a well-known, blended herbal formula. This study was carried
      out to investigate the beneficial effects of OJS on atherosclerosis in vitro and
      in vivo. Western-diet-fed apolipoprotein-E gene-deficient mice (ApoE -/-) were
      used for this study for 16 weeks, and their vascular dysfunction and inflammation
      were analyzed. OJS-treated ApoE -/- mice showed lowered blood pressure and
      glucose levels. The levels of metabolic parameters with hyperlipidemia attenuated
      following OJS administration. Hematoxylin and eosin (H&E) staining revealed that
      treatment with OJS reduced atherosclerotic lesions. OJS also suppressed the
      expression of adhesion molecules and matrix metalloproteinases (MMPs) compared to
      Western-diet-fed ApoE -/- mice and tumor necrosis factor-alpha (TNF-alpha)
      stimulated human umbilical vein endothelial cells (HUVECs). Expression levels of
      MicroRNAs (miRNA)-10a, -126 3p were increased in OJS-fed ApoE -/- mice. OJS
      significantly increased the phosphorylation of endothelial nitric oxide synthase
      (eNOS) and protein kinase B (Akt), which are involved in nitric oxide (NO)
      production. OJS also regulated eNOS coupling by increasing the expression of
      endothelial GTP Cyclohydrolase-1 (GTPCH). Taken together, OJS has a protective
      effect on vascular inflammation via eNOS coupling-mediated NO production and
      might be a potential therapeutic agent for both early and advanced
      atherosclerosis.

PMID- 30200676
TI  - Survivability Prediction of Colorectal Cancer Patients: A System with Evolving
      Features for Continuous Improvement.
AB  - Prediction in health care is closely related with the decision-making process. On
      the one hand, accurate survivability prediction can help physicians decide
      between palliative care or other practice for a patient. On the other hand, the
      notion of remaining lifetime can be an incentive for patients to live a fuller
      and more fulfilling life. This work presents a pipeline for the development of
      survivability prediction models and a system that provides survivability
      predictions for years one to five after the treatment of patients with colon or
      rectal cancer. The functionalities of the system are made available through a
      tool that balances the number of necessary inputs and prediction performance. It
      is mobile-friendly and facilitates the access of health care professionals to an
      instrument capable of enriching their practice and improving outcomes. The
      performance of survivability models was compared with other existing works in the
      literature and found to be an improvement over the current state of the art. The
      underlying system is capable of recalculating its prediction models upon the
      addition of new data, continuously evolving as time passes.

PMID- 30200678
TI  - Editorial.

PMID- 30200677
TI  - Development of the urostyle during metamorphosis in five species of anurans.
AB  - Normal development of the urostyle is described during late stages of
      metamorphosis in five species of anurans: Xenopus laevis (Daudin), Bufo
      americanus Holbrook, Pseudacris triseriata (Wied), Hyla chrysoscelis Cope, and
      Rana pipiens Schreber. The developing urostyle of all five species is composed of
      essentially the same cartilaginous elements: one pair of basidorsals above the
      notochord and the subtended hypochord. Among the five species there is variation
      in such details as the number of spinal nerve foramina and the degree of fusion
      of the basidorsals; however, both the hypochord and basidorsals are very similar
      in all five genera examined. Consideration of the literature suggests that
      contradictory descriptions of the developing urostyle result from (1) varied
      methods of study (alizarin-staining of whole specimens or serial cross-sections),
      (2) the variety of species examined, and (3) the particular stage of development
      of the tadpole described by an investigator.

PMID- 30200679
TI  - Effects of germanium on the morphology of silica deposition in a freshwater
      sponge.
AB  - The effect of germanium on the secretion of siliceous spicules by the freshwater
      sponge Spongilla lacustris was investigated by exposing germinating and hatching
      gemmules to varying concentrations of germanium (Ge) in the presence of silicon
      (Si). Results were analyzed quantitatively and qualitatively and demonstrate that
      a [Ge]/[Si] (= molar ratio) of 1.0 completely inhibits silicon deposition.
      Intermediate ratios (0.5, 0.1, 0.01) which are permissive to spicule appearance
      result in fewer, shorter, and thinner spicules, in proportionately fewer
      microscleres, and in short bulbous megascleres. The size of the bulb increases
      with increasing [Ge]/[Si], while the length of the bulbous megascleres decreases
      with increasing [Ge]/[Si]. Microscleres do not demonstrate these graded responses
      suggesting that they are secreted in an all or none manner. Swellings produced in
      pond water and bulbs produced in germanium appear to decrease in size with time
      indicating a spreading of the accumulated silica. The effect of germanium on
      spicule secretion can be partially explained by its ability to uncouple the
      growth in length of the axial filament from the growth of the surrounding
      silicalemma. Under these conditions excess silicalemma is produced in which
      silica accumulates as bulbs in short spicules. Continuous exposure to Ge is
      necessary to produce this altered morphology. It is conjectured that the bulbs
      may be retained due to an inhibition of spreading. which in turn may be caused by
      the incorporation of germanium into the silica.

PMID- 30200680
TI  - Chemoreceptors in the cibario-pharyngeal pump of the cabbage looper moth,
      Trichoplusia ni (Lepidoptera: Noctuidae).
AB  - The structure of contact chemoreceptors in the cibariopharyngeal pump of the moth
      Trichoplusia ni (Lepidoptera: Noctuidae) is described. Two types of receptors
      designated A and B are located on the floor of the pump. Two groups of 9-12 A
      receptors are located in the anterior part of the pump, and two groups of two B
      receptors are in the posterior part of the pump. Five sensory dendrites extend to
      the tip of each A receptor and four to each B receptors. Available evidence
      indicates that these receptors are contact chemoreceptors and do not serve as
      mechanoreceptors. The receptors are compared to those of other insects.

PMID- 30200681
TI  - Growth and differentiation of secondary malpighian tubules in the cockroach,
      Periplaneta americana.
AB  - Four differentiated Malpighian tubules (primary tubules) extend from the junction
      of the midgut and hindgut in newly hatched Periplaneta americana. Secondary
      tubules begin to develop near the base of the primary tubules before hatching and
      successive nymphal molts. The newly initiated tubules undergo cell division and
      extensive elongation through the middle of the following intermolt period. During
      this time, the cells of the distal, middle, and lower middle tubule regions are
      surrounded by a cellular sheath, have few cytoplasmic processes extending along
      their basal surfaces, have a small or nonexistent lumen, and contain extremely
      dilated cisternae of endoplasmic reticulum. The cellular sheath differentiates
      into the muscle which coils around the mature tubule. Tubules which begin
      development toward the end of one intermolt period begin to undergo
      cytodifferentiation toward the end of the next intermolt period. By the middle of
      an additional intermolt period, the basal infoldings and microvilli of cells in
      the distal, middle, and lower middle regions have the conformations typical for
      those regions in differentiated tubules; granular concretions and stellate cells
      are present within the middle region of the tubule.

PMID- 30200682
TI  - Fibrous and adhesive components of the orb webs of Araneus trifolium and Argiope
      trifasciata.
AB  - The minimum number of secretion products used by the spiders Araneus trifolium
      and Argiope trifasciata to construct their orb webs has been established by
      selective enzyme digestion and histochemical staining, as well as differential
      isotope localization in these webs. Three fiber types are present in the webs:
      (a) a major fiber found throughout the web, (b) a minor fiber found only in
      radial threads, and (c) the core fibers of the sticky spiral thread. Three
      nonfibrous secretions are found on these fibers. These include a water soluble
      viscid coating of the sticky spiral and two adhesives which fasten the threads of
      the web together; one found only at junctions of sticky spiral and radial threads
      and the other at all other thread connections. The possible glandular sources of
      these secretions are discussed.

PMID- 30200683
TI  - Fine structural studies of the nervous system and the apical organ in the planula
      larva of the sea anemone Anthopleura elegantissima.
AB  - The nervous system of the planula larva of Anthopleura elegantissima consists of
      an apical organ, one type of endodermal receptor cell, two types of ectodermal
      receptor cells, central neurons and nerve plexus. Both interneural and
      neuromuscular synapses are found in the nerve plexus. The apical organ is a
      collection of about 100 long, columnar cells each bearing a long cilium and a
      collar of about 10 microvilli. The cilia of the apical organ are twisted together
      to form an apical tuft. The ciliary rootlets of the apical organ cells are
      extremely long, reaching to the basal processes of the cells adjacent to the
      mesoglea. All three types of sensory cells are tall and slender in profile and
      are identified by the presence of one or more of the following features:
      microtubules, small vesicles, membrane-bound granules and synapses. The
      interneurons are bipolar cells with somas restricted to the aboral end, adjacent
      to the apical organ. All synapses observed are polarized or asymmetrical. A
      diagram including all the elements of the nervous system is presented and the
      possible functions of the nervous system are discussed in relation to larval
      behavior.

PMID- 30200684
TI  - Countercurrent blood vessel arrangement in beaver (Castor canadensis).
AB  - The vascular anatomy of five beavers (Castor canadensis) was studied by
      dissection and injection of arteries and veins with vinyl acetate. There is
      extensive countercurrent arrangement of arteries and veins distal to and
      including the common iliac artery and veins. Two types of countercurrent vessels
      occur (1) a venae comitantes type in which two or three veins surround a central
      artery, and (2) a modified rete type. The retia are located proximal to the large
      flat tail and the webbed hind feet. Two bypass veins are described for the feet
      and tail and the significance of these structures in temperature regulation is
      stressed.

PMID- 30200685
TI  - Comparative cardiac anatomy of the reptilia. III. The heart of crocodilians and
      an hypothesis on the completion of the interventricular septum of crocodilians
      and birds.
AB  - The heart of Crocodylus porosus is described, and deemed to be typical of living
      crocodilians after examination of the hearts of Alligator mississippiensis,
      Caiman crocodilus ssp., Crocodylus johnstoni and Crocodylus n. novaeguineae. Some
      inconsistencies between the anatomy and supposed patterns of blood flow are
      discussed. The crocodilian heart is compared with, and seen as an advancement of,
      the heart of non-crocodilian reptiles. The varanid ventricle is re-examined, as
      it appeared to contain many crocodilian features, along with the ophidian
      characteristics described previously. The broad similarities within the three
      groups are interpreted as adaptations towards a high pressure systemic
      circulation. Consequently varanids and snakes show the same left and right
      ventricles, as do crocodilians and birds. The evolution of the complete
      interventricular septum of crocodilians and birds appears to have involved three
      major trends: firstly, the development of a high pressure left ventricle and the
      fusion of most of the combined atrio-ventricular valve to the ostium of the right
      systemic artery; secondly, a line in which right to left shunting became
      gradually redundant and the vertical septum was completed to the aortico
      pulmonary septum (giving rise to the avian ventricle); and thirdly, a line in
      which right to left shunting became increasingly important, and the vertical
      septum completed to the interaortic septum (giving rise to the crocodilian
      ventricle). Perhaps the crocodilian ancestry included a crocodile that was far
      more aquatic than any extant species.

PMID- 30200686
TI  - Fine structure of the gills of some Indian air-breathing fishes.
AB  - A detailed account is given of the structure of the gills of Clarias batrachus,
      Heteropneustes (= Saccobranchus) fossilis, Channa punctata, Monopterus (=
      Amphipnous) cuchia and Boleophthalmus boddaerti, based upon light and electron
      microscopy. In all five species the basic organization into primary and secondary
      lamellae is apparent but the latter are very much more modified in Monopterus.
      Three main layers separate the water and blood on the surface of the secondary
      lamellae. The outer epithelium is usually two layered but may be multilayered
      close to the origin of the secondary lamellae from the gill filament. The
      basement membrane is relatively thin and a middle dense layer containing collagen
      fibrils separates two clear layers. The pillar cells, so characteristic of
      secondary lamellae, are present in all except Monopterus and flanges from these
      cells surround the blood channels with the exception of the marginal channels.
      The latter are lined by endothelial cells which line all the blood channels of
      Monopterus. The overall thickness of the three layers comprising the water/blood
      barrier ranges from 1.5 to 13 microns. A number of modifications to this basic
      organization can be related to the degree of dependence of the different species
      on air-breathing. Boleophthalmus is the only species commonly found in brackish
      water and its secondary lamellae have well developed lymphoid spaces between two
      layers of the epithelium. Special densely-stained regions of the pillar cell
      flanges were also present in this fish and may have a supporting function.

PMID- 30200687
TI  - Membrane production and yolk degradation in the early fly embryo (Calliphora
      erythrocephala meig.): An ultrastructural analysis.
AB  - Formation of nuclear envelopes during the last cleavage mitosis and the formation
      of the cell membranes during the cellularization of the blastoderm have been
      studied ultrastructurally in the blowfly egg. Dense bodies arising from yolk
      granules by budding could contain membrane material destined to be incorporated
      into the new membranes of the blastoderm. The presence of transitional structures
      indicates that these bodies can be converted into dark multivesicular bodies.
      Large amounts of endoplasmic reticulum are found around the mitotic nuclei.
      Clusters or branched chains of vesicles associated with this are interpreted as
      evidence for the formation of endoplasmic reticulum by the breakdown of dark
      multivesicular bodies. Nuclear envelopes of mitotic daughter nuclei probably
      originate from endoplasmic reticulum. The egg contains both intranuclear and
      extranuclear annulate lamellae. The main events of cytokinesis are furrow
      initiation and cell membrane growth during the slow first phase, but probably
      only cytokinetic movement during the rapid second phase. On the assumption that
      cell membrane growth occurs by incorporation of complete membrane pieces, the
      addition of coated vesicles and/or light multivesicular bodies is definitely most
      probable. Some intermediate profiles indicate that light and dark multivesicular
      bodies are related. The membrane needed for second phase cytokinesis could well
      be provided by the unfolding of surface microvilli and protuberances of the
      furrow canal.

PMID- 30200689
TI  - Keratin formation and barrier mechanisms in the epidermis of Natrix natrix
      (Reptilia: Serpentes): An ultrastructural study.

PMID- 30200688
TI  - Leucophores and iridophores of Fundulus heteroclitus: Biophysical and
      ultrastructural properties.
AB  - Classical light microscopic studies on pigmentation of Fundulus heteroclitus
      (killifish) indicated that there are three groups of light reflecting cells; one
      group on the surface of scales reflects white light, while two other deeper
      groups (the melaniridophores and the stratum argenteum) are iridescent. The
      results presented here show that: (1) The scale leucophores reflect white light
      by a Tyndall light-scattering mechanism, by virtue of the presence of randomly
      oriented organelles of "novel" morphology. (2) The iridophores of the
      melaniridophores contain stacks of irregularly-spaced, large reflecting platelets
      which function as an imperfect multiple thin layer interference system. (3) The
      stratum argenteum consists of a continuous layer(s) of iridophores with
      reflecting platelets which are so regularly packed as to approach an ideal
      multiple thin layer interference system. (4) In all three types of light
      reflecting cells, the dimensions and packing (orientation) of the reflecting
      organelles satisfactorily account for the chromogenic properties of the cells,
      including colors as viewed under transmitted, reflected, or polarized light. (5)
      The spacial relationships between these light reflecting cells and adjoining
      melanophores are different for each type of light reflecting cell. Furthermore,
      we propose to replace the term reflecting platelet with refractosome.

PMID- 30200690
TI  - Microanatomy of the lung parenchyma of a tegu lizard Tupinambis nigropunctatus.
AB  - The combined techniques of light microscopy, scanning (SEM) and transmission
      (TEM) electron microscopy were used for the first time to study the structure of
      unicameral lungs of a Tegu lizard (Tupinambis nigropunctatus). The lungs are
      prolate spheroid bags with blood supplied by superficial branches of a dorsal
      pulmonary artery and returned by diffuse, more deeply located veins. The primary
      bronchus enters the medial aspect near the apex of the lung. The lung wall is
      composed of trabeculae: (1) arranged in a faviform pattern, (2) forming
      individual faveoli (gas exchange chambers) which appear deepest in the cranial
      one-half of the lung, (3) all of which have a smooth muscle core overlain by
      either a ciliated or nonciliated epithelium. A ciliated epithelium lines the
      luminal surfaces of the large primary trabeculae and parts of smaller secondary
      trabeculae; it is composed of cone-shaped cells with ciliated-microvillous
      surfaces, and of columnar serous secreting cells. Nonciliated epithelium covers
      the luminal surface of portions of some secondary trabeculae, abluminal surfaces
      of primary and secondary trabeculae and all surfaces of the small tertiary
      trabeculae forming the faveoli. The nonciliated epithelium overlies an extensive
      superficial capillary network. The blood-gas barrier (0.7-1.0 MUm thick) is
      composed of a thin cytoplasmic flange of Type I pneumonocytes, a thick
      homogeneous basal lamina and an attenuated endothelial cytoplasm. Numerous
      surfactant-producing Type II pneumonocytes are closely associated with the Type I
      pneumonocytes. The nonrespiratory ciliated epithelium may function in
      humidification of air and clearing of the lungs.

PMID- 30200691
TI  - Ordered membrane particles in rhabdomeric microvilli of the housefly (Musca
      domestica L.).
AB  - Rhabdomeric microvilli of the housefly were freeze-fractured (FF) and thin
      sectioned (TS) for ultrastructural examination. Ordered files of closely packed
      membrane particles (82 A wide, 250 A long) were seen (FF) on the microvillar
      membrane (usually E face). The long axis of each particle was canted about 45
      degrees  to that of the microvillus. Occasionally particles in this array
      appeared on the P face. It is hypothesized that ordered particles may represent
      either a photopigment precursor stock, a second photolabile pigment, or the newly
      discovered sensitizing, UV-absorbing, photostable visual pigment. In the
      underlying membrane leaflet (P face) were found spherical (85 A diameter)
      unoriented particles in a concentration of about 6,000/MUm2 . The size, shape and
      density of these structures are compatible with those of rhodopsin particles.
      These particles also covered the basal area of each microvillus. The findings
      from TS material were difficult to correlate with those from FF replicas. At high
      magnification the former showed that the plasma membrane of the transected
      microvillus is composed of spherical, hollow subunits (averaging 43 A diameter),
      sometimes fused to form double, 86 A units. These substructures were closely
      packed and continuous around the microvillus. This beaded plasma membrane, in
      rare cases, was doubled around the microvillus. In other instances the plasma
      membranes were continuous between neighboring microvilli. The physiological
      implications of these ultrastructural features are discussed.

PMID- 30200692
TI  - Histochemical and ultrastructural features of the aorta of the slug (Limax
      maximus).

PMID- 30200693
TI  - Morphology, histochemistry and physiology of the major salivary glands in the
      echidna Tachyglossus aculeatus (Monotremata).
AB  - The three major salivary glands of the monotreme echidna are described. The
      parotid is a typical serous gland with tubulo-acinar secretory endpieces and a
      well-developed system of striated ducts. The mandibular gland, although light
      microscopically resembling a mucous gland, secretes very little glycoprotein. Its
      cells are packed instead with serous granules, resembling in fine structure the
      "bull's eye" granules in the mandibular gland of the European hedgehog Erinaceus
      europaeus. The sublingual glands secrete an extremely viscous mucous saliva.
      Expulsion of this saliva through the narrow ducts is probably aided by
      contraction of the extensive myoepithelial sheaths surrounding the secretory
      tubules. Application of the glyoxylic acid induced fluorescence method failed to
      demonstrate adrenergic innervation in any of the glands.

PMID- 30200694
TI  - Nature and cellular origin of the adhesive coats of the lamprey egg (Petromyzon
      marinus).
AB  - Cell surface coats are important in adhesion and other cellular activities. The
      lamprey egg possesses a surface coat that has been divided into two
      morphologically and functionally distinct regions. The amorphous apical tuft
      forms a cap over the animal pole, while the elaborately-textured adhesive coat
      covers the ventral two-thirds of the egg. This latter area is composed of
      saccules that form rosettes over the egg surface and is derived from the remains
      of specialized follicular cells which break down during ovulation. The adhesive
      qualities of these coats may be inhibited or abolished by various proteins and
      sulphydryl-blocking agents, thereby implicating, as a possible source of this
      adhesion, classes of acid and sulphated glycoproteins and glycosaminoglycans
      which occur on the egg surface.

PMID- 30200695
TI  - Ontogeny of melanophore patterns in haploid and diploid embryos of the frog,
      Bombina orientalis.
AB  - Diploid tadpoles of the discoglossid frog, Bombina orientalis, possess a
      distinctive rectangular network of epidermal melanophores. The ontogeny of this
      network was examined and utilized as a model for the comparison of tissue
      integrity and cellular interactions in diploid and haploid embryos. During the
      process of network formation in diploids, a variety of melano-phore-melanophore
      interactions was observed. These included temporary contacts between neighboring
      melanophore processes, deviations of processes toward neighboring melanophores,
      and lateral extensions between closely situated, parallel processes originating
      from different cell bodies. None of these intercellular interactions were seen in
      haploid embryos. Haploid melanophores displayed fewer cytoplasmic extensions,
      appeared to be randomly oriented, and failed to establish the ordered network
      seen in diploid embryos. It was also discovered that, in comparison with diploid
      tissues, relative densities of melanophores and epithelial cells were not
      uniformly regulated in haploid embryos. These findings are interpreted as
      indicating that haploid embryos possess fundamental cell and tissue defects, and
      that the "haploid syndrome" is likely based on more than one or a few defective
      physiological functions.

PMID- 30200696
TI  - Origin and fate of germ cells in male and female embryos of Haplothrips verbasci
      (Osborn) (Insecta, Thysanoptera, Phlaeothripidae).
AB  - Comparison of germ cells in male and female embryos of the arrhenotokous thrips,
      Haplothrips verbasci, yields the following observations: A mean of 11 cleavage
      energids enter the posterior pole plasm of the egg after the sixth cleavage
      division and apparently become pole cells when they take up polar granules in
      their cytoplasm. The cells proliferate asynchronously prior to and during
      anatrepsis to yield a mean of 36 germ cells in male embryos and 31 in females.
      Visible sexual differentiation of germ cells begins during germ band elongation
      and is completed shortly after the appearance of appendages. Female germ cells
      are larger than those of the males and may contain two nucleoli. The germ cells
      separate into two groups just before katatrepsis and mesodermal cells collect
      about these to form the primary epithelial sheaths of the gonads and the
      primordia of the gonoducts shortly after revolution is completed. Each gonad
      contains a mean of 13 germ cells in male embryos and 7 in females - a number that
      persists until mitosis resumes after hatching. During ketatrepsis, a mean of 11
      germ cells in male embryos and 2.6 in females fail to be enclosed within the
      gonads, become dispersed in the yolk and perhaps transform into vitellophages.
      Germ cell development in H. verbasci embryos resembles similar events taking
      place in psocid embryos, providing additional evidence for a close phylogenetic
      relationship between Thysanoptera and Psocoptera.

PMID- 30200697
TI  - [Statues and research strategy of molecular breeding in Artemisia annua].
AB  - Malaria is one of the three most deadly diseases in the world. Artemisinin is the
      first line and effective drug for treating malaria, and only can be extracted
      from Artemisia annua. Therefore, it is of great significance to cultivate new
      varieties of A. annua with high artemisinin content. Based on the germplasm bank
      and the whole genome, transcriptome and genetic map, the authors can explore high
      quality genes, stress-resistant genes and genetic markers which have been used
      for rapid breeding of superior varieties of A. annua. So these methods of
      molecular breeding will become the main breeding direction of A. annua in the
      future. The breeding times of new varieties of A. annua can be shortened with
      molecular breeding technology. Based on the genetic background and the current
      situation of molecular breeding of A. annua, the strategy and technical route of
      molecular breeding were discussed and worked out in this paper, which provided a
      guidance and scientific reference for molecular breeding of A. annua in the
      future.

PMID- 30200698
TI  - [Protective effects of artesunate combination on experimental cerebral malaria
      and nerve injury].
AB  - Cerebral malaria (CM) is the leading cause of death in children under 5 years in
      Africa, severe neurological sequelae may occur in surviving children. Although
      artesunate has made breakthrough progress in the clinical treatment of CM, the
      clinical problems of high mortality and high morbidity have not yet been
      completely resolved. In this study, an experimental cerebral malaria (ECM) model
      was established by infecting C57BL/6 mice with Pb ANKA (Plasmodium berghei ANKA)
      to compare parasitemia level, survival rates, and rapid murine coma behavior
      scale scores, cerebral microvascular obstruction, haemozoin deposition in the
      liver, body temperature and weight to investigate the anti-cerebral malaria
      effect of the artesunate compound combination. The results showed that the
      artesunate compound combination could improve the survival rate of Pb ANKA
      infected mice, reduce the level of parasitemia, effectively improve the symptoms
      of ECM neurological injury, reduce cerebrovascular obstruction and haemozoin
      deposition in the liver, and also significantly improve body temperature, weight
      and other basic indicators. The results showed that the artesunate compound
      combination improved the pathological changes and neurological damage caused by
      CM. It is expected to provide a theoretical basis for human cerebral malaria
      patients in clinical adjuvant therapy.

PMID- 30200699
TI  - [Application of three artemisinin derivatives in neuropathic pain: evaluating co
      curation of nociceptive and emotional syndromes in spinal cord ligation mice].
AB  - In this study, on aspects of the nociceptive, anxiety and depressive syndromes in
      neuropathic pain (NP), the effects of dihydroartemisinine (DHA), artesunate (ART)
      and artemether (ARTN) (40 mg.kg-1) were analyzed in the spinal cord ligation
      (SNL) mice. Clinical equivalent dose of the first-line drug for NP, pregabalin
      (PGB, 25 mg.kg-1) and amitriptyline (ARP, 20 mg.kg-1), were used as positive
      controls. General, from day 7 to 14, significant remissions of the nociceptive,
      anxiety and depressive behaviors were achieved by DHA, ART and ARTN separately.
      Moreover, on day 14, on aspects of the nociceptive behaviors, analyzed 1.5 h
      after the gavage administration, no significant difference between the shamed
      mice and mice administrated with DHA, ART and ARTN was detected; analyzed 3 h
      after the gavage, significant decreases of pain thresholds in ARTN, but not in
      DHA nor ART group, were detected as compared with thresholds measured 1.5 h;
      analyzed 24 h after gavage, pain thresholds in DHA, ART and ARTN were still
      higher than PGB, in spite of the significant decreases as compared to Sham group.
      On aspects of the anxiety and depressive behaviors, no significant difference was
      detected between the shamed mice and mice administrated with DHA nor ART.
      However, differences still remained between the shamed ones and ones
      administrated with ARTN. Preliminarily, the effects of DHA, ART and ARTN were
      consolidated in SNL mice. On aspects of the duration of analgesic effects and the
      control of negative emotion, ART and ARTN were proven more favorable than ARTN.

PMID- 30200700
TI  - [Prokaryotic expression, purification and crystallization of CYP71AV1, key enzyme
      in artemisinin biosynthesis].
AB  - Malaria is a worldwide epidemic that extensively endangers health of human
      beings. Before artemisinin was developed to treat with malaria, about 400 million
      person-time of malaria infections and at least 1 million deaths from malaria were
      reported in the world every year. Thus malaria has been listed as one of the
      world's three major death diseases by the WHO. The discovery of artemisinin by
      Chinese scientists created a novel therapy approach to treat with malaria
      effectively. Amorpha-4,11-diene oxidase is a plant cytochrome P450 enzymes, i.e.
      CYP71AV1, which catalyzes each of the three oxidation steps from amorpha-4,11
      diene to form artemisinic acid, the intermediate of artemisinin. CYP71AV1 is the
      key enzyme in artemisinin biosynthesis. By constructing the prokaryotic
      expression vector pCWOri(+)-CYP71AV1, functional expression and purification of
      complementary CYP71AV1 were performed. The enzyme activity was monitored by CO
      differential spectrum assay and the heme-based activity analysis. The preliminary
      crystallization condition was obtained by crystallization screening. These
      studies provide basis for resolving the crystal structure of CYP71AV1 and for
      producing artemisinin in large scale through biosynthetic biology approach, and
      will provide references for over expression, purification and crystallization of
      other plant P450 enzymes.

PMID- 30200701
TI  - [Research in technical regulations for production of pollution-free Chinese
      herbal medicines].
AB  - Aimed to solve the issues of pesticide residue, heavy metal contents and harmful
      elements in the productive process of Chinese herbal medicines, the research team
      built the technical regulations for production of pollution-free Chinese herbal
      medicines. This regulation included the environment of production area, the
      process of production, quality of products etc., which were the key steps
      controlled the quality of Chinese herbal medicines. The environment of production
      area was selected according to the ecological factors which were stipulated by
      Ecological Suitability Regionalization of Chinese herbal medicines (second
      edition). The quality of air should be attain the one or two levels of GB/T3095
      2012 standard values. The cultivation soils should reach to the one or two levels
      of GB15618 and NY/T391 standard values. The quality of irrigation water should
      accord with the stipulation of GB5084-2005. Aimed to the production of Chinese
      herbal medicines, disease-resistant and superior varieties which were suitable to
      the local stations should be selected, and the breeding of superior seeds and
      seedlings should be strengthened. Additionally, rational fertilizer application
      of pollution-free Chinese herbal medicines should be conformed to the principles,
      requirements, and the kinds of fertilizers allowed or limited for use, which were
      stipulated by the standard of DB13/T454. Furthermore, the plant protection policy
      of priority to prevention and synthetical prevention should be followed;
      improving ecological environment and strengthening cultivation management should
      be served as the basics. Agricultural measures, and biological and physical
      control strategies should be preferred to use; and high toxicity, residue
      pesticide and its mixture should be inhibited; the use of chemical pesticides
      should be minimized and then to decrease contamination and residue. Additionally,
      the quality of products should be reached to the standard of pollution-free
      Chinese herbal medicines; high toxicity and detection rate of pesticide residues
      and the contents of heavy metal and harmful elements (e.g. plumbum, cadmium,
      mercury, arsenic and cuprum) should accord with the common criteria of pollution
      free Chinese herbal medicines. Application of technical regulations for
      production of pollution-free Chinese herbal medicines guarantees significantly
      social, economic and ecological benefits.

PMID- 30200702
TI  - [Recent research progress of selenium polysaccharides from medicinal plants].
AB  - Selenium polysaccharides (Se polysaccharides) are a kind of organic selenium
      compounds which obtain the activities from Se and polysaccharides. Comparing to
      Se or polysaccharides, Se polysaccharides exhibit improved biological activities
      and are more prone to be absorbed by human bodies, therefore, they have been
      widely used in medical applications, such as immunomodulation, anti-tumor, anti
      oxidation, anti-aging. Due to their unique pharmacological activities, Se
      polysaccharides from medicinal plants have gradually become a research hotspot.
      However, only a few of Se polysaccharides have been separated and purified in
      recent years. The structure of polysaccharides is also very complex, therefore,
      determination of the chemical structure and mechanism of bioactivity of Se
      polysaccharide in vivo remain to be further studied. This article systematically
      introduced the main source and biological activities of Se polysaccharides from
      medicinal plants. The purpose of this review is to provide a basis for the
      further research of Se polysaccharides.

PMID- 30200703
TI  - [Safety evaluation and risk control measures for Aconiti Kusnezoffii Radix].
AB  - Through the comprehensive and systematic research of domestic and overseas
      literature and information, we studied ancient original records on Aconiti
      Kusnezoffii Radix and its toxicity, analyzed related adverse cases and the animal
      toxicity experiments in recent years, then systematically analyzed the safety of
      Aconitum and its preparations, and finally we summarized the clinical
      characteristics and potential risk factors related to the safety of Aconitum. A
      report on adverse events of Aconitum in 76 patients with myocardial damage and
      renal damage accounting for 53.9% and 42.1% respectively, indicated that the
      safety problems of Aconitum may be related to heart toxicity and liver-kidney
      toxicity. Aconitum had complex compositions, and based on the animal experiments,
      Aconitum decoction had the highest toxicity at 2 h, and it reduced significantly
      at 4 h, which showed that the toxic components mainly depend on the hydrolysis or
      the decomposition degree of diester diterpenoid alkaloids. According to the
      toxicity study, Aconitum toxicity might occur in cardiovascular system, nervous
      system, kidney, embryo, reproductive system, and it was contraindicated in
      pregnant women. So far, specific antidote for aconitine poisoning is still a
      blank. The key for treatment is to correct arrhythmia timely and effectively,
      maintain stable vital signs, and meanwhile, give gastric lavage, intravenous
      fluid infusion and other therapies. So we suggest that the basic study for
      Aconitum toxicology should be strengthened, and the pharmacology and mechanism of
      toxicity, as well as the mechanism of processing for raising efficiency and
      reducing toxicity, should be further clarified to determine the quantity-effect
      relationship and eliminate safety hazards in using Aconitum.

PMID- 30200704
TI  - [Historical evolution and modern research progress on characteristic processing
      of porcine cardiac blood processed Salvia miltiorrhiza in Menghe medical school].
AB  - The porcine cardiac blood processed Salvia miltiorrhiza (PCB Danshen) is the
      characteristic processing of Menghe medical school and has been inherited for
      hundreds of years, commonly used in the treatment of brain ischemia-induced
      agitation, palpitation and phlegm confusing heart. Ancient and modern physicians
      believe that porcine cardiac blood is a guiding for heart nourishing drugs, which
      could enhance the effects of Salvia miltiorrhiza by nourishing and soothing the
      nerves. However, the material basis and processing mechanism of PCB Danshen are
      still unclear. This paper investigated the historical evolution and modern
      research of PCB Danshen, including the clinical application, the intention of
      clinic processing, the processing technology and recent research of PCB Danshen.
      In addition, the major problems and significance in research and development of
      PCB Danshen were further thought and prospected, hoping to provide basic data for
      material basis and processing mechanism of PCB Danshen, and provide effective
      support for inheriting and carrying forward the characteristic processing
      technology of Menghe medical school.

PMID- 30200705
TI  - [Identification and quality evaluation of Tripterygium wilfordii].
AB  - With the extensive clinical application of Tripterygium wilfordii, there are many
      counterfeit products on the market. Traditional technology can not effectively
      identify the authenticity of the traditional Chinese medicine. Therefore, a
      strategy of accurate identification and quality evaluation of Tripterygium based
      on DNA barcode and chemical fingerprint spectrum was established. Based on DNA
      barcode technology, HMMer annotation method of hidden Markov model and K2P model
      were used to analyze genetic distance.BLAST1, nearest distance and phylogenetic
      tree (NJ-tree) methods were used to assess the identification efficiency of the
      ITS2 barcode. The fingerprint of 27 T. wilfordii was established by UPLC-PDA
      method, and the similarity of the fingerprint of different sources was evaluated.
      The main components of T. wilfordii were determined by LC-MS/MS. The results
      revealed that the intraspecific genetic distances of T. wilfordii were lower than
      the interspecific genetic distances between T. wilfordii and its adulterants. The
      results of similarity search showed that ITS2 sequence was used to identify T.
      wilfordii and its adulterants. The clustering of T. wilfordii and its adulterants
      was clear in the tree of NJ cluster, and 12 of 27 samples were identified as true
      T. wilfordii.The chemical fingerprint spectrum research indicates that the
      feature one region can distinguish the false product of tripterygium glycosides
      more intuitively. The cluster analysis of HCA-thermal map showed that the
      contents of six active components of T. wilfordii from different habitats were
      significantly different, which could be used to evaluate the quality of T.
      wilfordii. This paper is of guiding significance for the accurate identification
      and quality evaluation of Tripterygium medicinal plants.

PMID- 30200706
TI  - [Physiological effects of cadmium stress on Astragalus membranaceus seedlings and
      alleviative effects of attapulgite clay on cadmium stress].
AB  - In this study we investigate the effects of cadmium stress on Astragalus
      membranaceus seedlings and the alleviative effects of attapulgite clay in growth
      substrate on cadmium stress to A. membranaceus seedlings. The results showed that
      the Y (II) (effective photochemical quantum yield of PSII photosynthetic),
      qP(photochemical quenching coefficient), ETR(the rate of non-cyclic
      electrontransport through PSII), and chlorophyll content of the leaves were
      significantly decreased with the increase of cadmium concentrations, while the
      cadmium content, non-photochemical quenching(NPQ, qN) of the leaves and cadmium
      content, MDA content, plasma membrane permeability, and the damage degree of root
      apical membrane of the roots were significantly increased. Simultaneously, the
      activities of APX(ascorbate peroxidase), SOD(superoxide dismutase),
      POD(peroxidase), CAT(catalase), soluble protein content, and soluble sugar
      content of roots were increased first but then decreased with the increasing
      cadmium concentration. Under the condition of without Cd stress, the attapulgite
      clay into the growth substrate did not significantly affect above physiological
      indexes of leaves, but significantly increased SOD activity and soluble sugar
      content of roots and decreased the MDA content, damage degree of root apical
      membrane of roots, while other physiological indexes did not significantly
      change. Under cadmium stress, the presence of attapulgite clay in the growth
      substrate significantly alleviated the cadmium-induced decreases Y (II), qP, ETR
      and chlorophyll content of leaves, and the CAT activity, soluble protein content,
      and soluble sugar content of roots. Under condition with cadmium stress, the
      presence of attapulgite clay significantly alleviated the cadmium-induced
      increases of leaves cadmium content, qN and NPQ, and the cadmium content, MDA
      content, plasma membrane permeability, damage degree of root apical membrane,
      SOD, POD, and APX activity of the roots. And, the alleviative effects of
      attapulgite clay on cadmium stress to A. membranaceus roots were more obvious
      with the increase of cadmium stress time. The above results showed that the
      addition of attapulgite clay into the growth substrate has certain alleviative
      effect on the cadmium stress to A. membranaceus seedlings.

PMID- 30200707
TI  - [Application of feedforward control strategy based on spectra of raw materials to
      optimize alcohol extraction process of Panax notoginseng].
AB  - In this work, we obtained the quality information of Panax notoginseng with near
      infrared spectroscopy in an efficient way. By combining the quality information
      of raw materials with process parameters in experimental design, quantitative
      relationship models were established between material quality information,
      process parameters and product quality of P. notoginseng, thus realizing the
      feedforward control of the alcohol extraction process. The quantitative models
      established have high robustness and satisfactory forecasting ability. With new
      batches of P. notoginseng introduced for the alcohol extraction process, the
      quality information of raw materials was rapidly obtained. Based on the
      established models, the process parameters were optimized according to the
      expected critical quality attributes (CQA), thereby reducing the fluctuation of
      product quality caused by raw material variation.

PMID- 30200708
TI  - [Effect of different concentrations of Gegen Qinlian decoction on expression of P
      glycoprotein and multi-drug resistance protein transporter in Caco-2 cells].
AB  - To investigate the effects of Gegen Qinlian decoction on the expression of P
      glycoprotein (P-gp) and multi-drug resistance protein (MRP) in epithelial cells
      of human colon adenocarcinoma Caco-2 cells.The effects of different
      concentrations of Gegen Qinlian decoction on the expression levels of p-gp and
      MRP1-6 mRNA in Caco-2 cells were detected by real time quantitative reverse
      transcriptase PCR (qRT-PCR).12 h after drug treatment (5.00 g.L-1), the
      expression levels of MDR1 and MRP1-6 were significantly down-regulated at
      concentration of 5.00 g.L-1; the mRNA expression levels of
      MDR1,MRP1,MRP2,MRP4,MRP5 and MRP6 were significantly down-regulated at
      concentration of 2.50 g.L-1; only the expression levels of MRP2 and MRP5 were
      significantly affected at concentration of 1.00 g.L-1. The results showed that
      the expression levels of MDR1 and MRP1-6 mRNA in Caco-2 cells could be down
      regulated in a dose-dependent manner. Gegen Qinlian decoction may reduce drug
      efflux by down-regulating the mRNA expression of cell transporters in Caco-2
      cell, and increase the time of drug action, thereby enhancing the bioavailability
      of chemotherapeutic drugs.

PMID- 30200709
TI  - [Determination of flavonoids constituents in epimedium total flavone capsule and
      research on its anti-osteoporosis activity].
AB  - To develop a rapid resolution liquid chromatography (RRLC) method for the
      simultaneous determination of epimedoside A, epimedin A1, epimedin A, epimedin B,
      epimedin C, icariin, baohuosideII, icarisideI, sagittatoside B, 2"-O-rhamnosyl
      icarisideII, and baohuosideIin epimedium total flavone capsule. At the same time,
      the effects of the above 11 compounds on osteogenic differentiation of MC3T3-E1
      cells were investigated by detecting the content of alkaline phosphatase (AKP).
      The results showed that baohuoside II had the highest activities, and both the
      activities of baohuoside II and icariside I were stronger than those of
      icariin.In this study, the content determination method of flavonoid glycosides
      was established, and the anti-osteoporosis effect of monomers was compared,
      providing technical support for the study of the pharmacodynamic and mechanism of
      Epimedium total flavone capsule.

PMID- 30200710
TI  - [Chemical study on Cassiae Semen processing procedure].
AB  - References and our previous experiment showed that the contents of glycosides
      were significantly decreased,while the contents of aglycones were significantly
      increased after processing of Cassiae Semen.It may be related to its glycosidases
      or the heating process. In order to investigate the reasons, high performance
      liquid chromatographic (HPLC) was used to study the effects of these two factors
      on contents of Cassiae Semen's main chemical components in processing. The
      results showed that glycoside hydrolases was present in Cassiae Semen and could
      rapidly hydrolyze glycosides from Cassiae Semen into aglycones in suitable
      temperature with sufficient water.However,it didn't show effect on contents
      change of main constituents in the procedure of Cassiae Semen processing.The
      reason for content decrease of glycosides and content increase of aglycones in
      processed Cassiae Semen was glycoside bond cracking to produce corresponding
      aglycone at high temperature.This study further provides basis for further
      revealing of the processing mechanism of Cassiae Semen.

PMID- 30200712
TI  - [Optimization of method for determination of Forsythia Fructus and discussion on
      the establishment of quality control standard for green (old) Forsythia Fructus].
AB  - In order to obtain the optimum method for content determination of Forsythia
      Fructus (FF), a variety methods for the sample preparation of FF were evaluated
      by the content determination methods of Chinese Pharmacopoeia. And an optimum
      method was screened and as follows: 30 times with 70% ethanol solution in
      ultrasonic extractor for half an hour. The method can achieve the best effect of
      simultaneously extracting forsythoside A and forsythin. Then, a HPLC method for
      simultaneous determination of forsythoside A and forsythin was established by
      methodology. The HPLC chromatographic conditions: the mobile phase consisted of
      acetonitrile (A)-0.4% acetic acid solution (B) with gradient elution [0-33
      min,15%A,33-43 min,15%-25%A,43-60 min,25% A] was at the flow rate of 1 mL.min-1,
      the column temperature was 25  degrees C, and the detection wavelength was 330
      and 277 nm. Moreover, the contents of forsythoside A and forsythin for 10 Green
      Forsythia Fructus (GF) and 5 Old Forsythia Fructus (OF) were determined by this
      method and Chinese Pharmacopoeia. The result not only displayed that the
      established method is effective, rapid, and simple, but also showed that the
      contents of forsythoside A and forsythin for GF and OF were significantly
      different. Which implied that the forsythoside A and forsythin limit standard for
      GF and OF should be controled by different values. This studies provide an
      important basis for the establishment of the content determination of FF and the
      quality control standard for GF and OF.

PMID- 30200711
TI  - [Two new flavonoid glycosides from leaves of Moringa oleifera].
AB  - Two new flavonoid glycosides, quercetin-3-O-(4-O-crotonyl)-beta-D-glucopyranoside
      (1) and quercetin-3-O-[6-O-(2E)-pentenoyl]-beta-D-glucopyranoside (2), along with
      nine known ones, isoquercetin (3), astragalin (4), quercetin-3-O-(6-O-acetyl)
      beta-D-glucopyranoside (5), kaempferol-3-O-(6-O-acetyl)-beta-D-glucopyranoside
      (6), quercetin-3-O-(6-O-crotonyl)-beta-D-glucopyranoside (7), kaempferol-3-O-(6-O
      crotonyl)-beta-D-glucopyranoside (8), vitexin (9), isovitexin (10), and
      isorhamnetin-3-O-beta-D-glucopyranoside (11), were isolated from the leaves of
      Moringa oleifera by various chromatographic technologies. Their structures were
      elucidated by spectroscopic methods including UV, IR, MS, and NMR. In addition,
      compounds 7 and 8 were isolated from this plant for the first time.

PMID- 30200713
TI  - [Response of volatiles of Artemisiae Argyi Folium to climatic factors].
AB  - Combined headspace solid-phase microextraction with gas chromatography-mass
      spectrometry (HS-SPME-GC-MS), this paper studied the volatiles of Artemisiae
      Argyi Folium that respectively collected from Kongdong, Huanglong, Ankang, Qichun
      and Tongbai,and then explored the influence of climatic factors on the main
      components of the volatiles. The results showed that 54, 52, 57, 47 and 55
      compounds were respectively identified from the leaves from five regions, mainly
      consist of monoterpenes, sesquiterpenoids and their oxygen-containing
      derivatives, a few aldehydes, alkanes and benzenes. It is different that the
      volatiles of Artemisiae Argyi Folium that collected in different habitats,
      neither composition nor content. There are total 18 kinds of compounds that exist
      in all five leaves. Eucalyptol, camphor, terpinen-4-ol, eugenol and caryophyllene
      could be considered to be the main conponents because of their efficacy or
      toxicity and relatively high content. Grey correlation analysis shows that the
      annual lowest temperature and annual sunshine duration have a great influence on
      the content of eucalyptol and camphor; the effect of annual precipitation and
      annual accumulated temperature on the content of terpinen-4-ol and caryophyllene
      was relatively significant; while the annual sunshine duration and the annual
      highest temperature are the main influencing factors for eugenol. The research
      suggests that long-day and extreme temperature may be more conductive to the
      accumulation of volatiles. According to the laws of effect of climatic factors on
      volatiles, we can optimize the cultivation conditions and select suitable
      locality to improve the quality of Artemisiae Argyi Folium.

PMID- 30200714
TI  - [Mechanism of lysosome-mediated eradication activity of macrophages on specific
      anti-Helicobacter pylori of patchouli alcohol].
AB  - The aim of this paper is to investigate the effect of patchouli alcohol in
      enhancing Helicobater pylori's action in eradicating macrophages and its
      mechanism. H. pylori was co-cultured with macrophages at a ratio of MOI=100 in
      different concentrations of patchouli alcohol. The effect of patchouli alcohol in
      eradicating macrophages was detected by agar dilution method. The effect of
      patchouli alcohol on NO and myeloperoxidase (MPO) levels in macrophages were
      measured by H. pylori by biochemical methods. Patchouli alcohol effect on H.
      pylori-induced pro-inflammatory gene expression and protein secretion in
      macrophages were detected by RT-qPCR and ELISA method. The eradication of H.
      pylori has significantly enhanced, and the destabilization of lysosomes has been
      reversed. Meanwhile, patchouli alcohol has an effect in inhibiting pro
      inflammation and oxidation. The mechanism of patchouli alcohol in eradicating H.
      pylori and resisting oxidative stress may be associated to the blocking of
      bacteria escape lysosome combination procedures.

PMID- 30200716
TI  - [Chronic hepatotoxicity evaluation of Chinese medicinal herb Zishen Yutai pill
      prepared from Polygoni Multiflori Radix preparata in dogs].
AB  - To study the chronic hepatotoxicity of Chinese medicine Zishen Yutai pill (ZYP)
      prepared from Polygonum multiflorum with the recommended dosage in normal Beagle
      dogs. Low, middle and high doses of ZYP (1.5, 3.0, 6.0 g.kg-1; i.e. 3*, 6* and
      12* equivalent doses) were given orally to dogs for 39 consecutive weeks. At the
      same time, the same volume of deionized water was used as the solvent control
      group, one time a day. The general condition of the animals was observed every
      day during the period of administration, and the blood was collected before and
      13, 26, 39, 43 weeks after administration to detect the biomarkers related to the
      hepatotoxicity of the dog serum. 2/7, 3/7 and 2/7 animals were dissected after
      13, 39, and 43 weeks of administration to observe the pathological changes of the
      animal organs, weigh the mass of main organs and conduct pathological examination
      of the liver. As compared to the solvent control group, 11 liver hepatotoxicity
      traditional biomarkers such as ALT, AST were found no ZYP-related changes at
      month 3, 6, 9 of the administration and month 1 in recovery period; There was no
      significant difference in liver viscera index and liver pathology. Therefore, no
      obvious hepatotoxicity was shown by ZYP administered up to 6.0 g.kg-1 for 9
      months in normal dogs at doses of 1.5, 3.0, and 6.0 g.kg-1.

PMID- 30200715
TI  - [Effect of Fuzi Lizhong decoction in reducing liver injury of rats with non
      alcoholic fatty liver via activating AMPK and suppressing NF-kappaBp65 pathway].
AB  - To investigate the protective effect and relevant mechanism of Fuzi Lizhong
      decoction (FZLZD) on liver of rats with non-alcoholic fatty liver disease
      (NAFLD), totally 32 male SPF Wistar rats were randomly divided into 4 groups:
      control group, model group, Yishanfu (YSF) group (200 mg.kg-1.d-1) and FZLZD
      group (10 g.kg-1.d-1), with 8 rats in each group. Rat model of NAFLD was prepared
      through the intragastric administration with fat emulsion for 4 weeks. After the
      successful modeling, rats in each administration group were continuously
      administered for 4 weeks. After 8 weeks, the rats in each group were put to
      death, and the pathological changes in liver tissue were detected by HE staining.
      Automatic biochemical analyzer was used to detect fasting serum lipid levels (T
      Chol, TG, LDL-C, HDL-C) and liver functions (ALT, TP, ALB) of rats in each group.
      The rat liver index was calculated by weighing method. Enzyme-linked
      immunosorbent assay (ELISA) was used to detect the secretion of inflammatory
      cytokines TNF-alpha and IL-6 in liver tissue. Real-time quantitative PCR (qRT
      PCR) was used to detect the mRNA expressions of fat metabolism-related factors
      SREBP-1c and FASN in liver tissue. Western blot was used to detect the p-AMPK and
      p-NF-kappaBp65 protein expressions in liver tissue. The results of HE staining
      showed that compared with the control group, the pathological changes in liver
      tissue in the model group rats were obvious; specifically, the outline of hepatic
      lobule was unclear, the hepatic cells showed diffuse steatosis of adipose tissue,
      and were accompanied by inflammatory infiltration, nuclear condensation, coloring
      deep; compared with the model group, liver lesions of all of the treatment groups
      were significantly alleviated; especially, the FZLZD group showed the most
      significant degree of remission. The results of serum test showed that the levels
      of serum lipids (T-Chol, TG, LDL-C, HDL-C), liver functions (ALT, TP, ALB) and
      liver index in model group were significantly higher than those in control group
      (P<0.01); compared with the model group, the indexes of serum lipid and liver
      function of rats in each treatment group were significantly decreased (P<0.01),
      and those in FZLZD group were significantly decreased (P<0.05), while those in
      YSF group were not significantly changed. The results of ELISA and qRT-PCR showed
      that compared with the control group, the secretion levels of TNF-alpha, IL-6 and
      the mRNA levels of SREBP-1c and FASN in the liver tissue of model group rats were
      significantly increased (P<0.01); compared with model group, the secretion levels
      of TNF-alpha, IL-6 and the mRNA levels of SREBP-1c, FASN in liver tissue of rats
      in each treatment group were significantly decreased (P<0.01); compared with YSF
      group, the secretion levels of TNF-alpha and IL-6 and the mRNA levels of SREBP-1c
      and FASN in FZLZD group were significantly different (P<0.01). Western blotting
      showed that compared with the model group, the protein expression of p-AMPK in
      liver tissue of rats in FZLZD group was significantly increased (P<0.01), while
      the protein expression of p-NF-kappaBp65 was significantly decreased (P<0.01).
      FZLZD can significantly improve hepatic pathological changes, reduce serum lipid
      levels, promote liver function and liver index in NAFLD rats, which may be
      associated with the activation of the AMPK pathway and thereby the inhibition of
      the expressions of SREBP-1c and FASN, and the inhibition of the NF-kappaBp65
      pathway and thereby the reduction of the release of inflammatory factors.

PMID- 30200717
TI  - [Intestinal absorption properties of ponicidin by single pass perfusion model in
      rats].
AB  - To determine the absorption properties and study the intestinal absorption
      kinetics of poncidin in rats. In situ single pass perfusion model was combined
      with High Performance Liquid Chromatography-Mass Spectrometry (HPLC-MS/MS) method
      to investigate the intestinal absorption characteristics and calculate absorption
      parameters with aspects of drug absorption, concentration and perfusion medium.
      The absorption of poncidin under acid condition at pH 6.5 was more stable, where
      intestinal enzymes showed little influence on metabolism, and the absorption was
      significantly higher than that in pH alkaline condition at pH 8.0 (P<0.05). Drug
      concentrations had no significant influence on absorption rate constant of the
      same intestinal segment Ka and apparent permeability coefficient Papp values of
      poncidin. Different concentrations of poncidin showed no significant differences
      in the Ka and Papp values among duodenum, jejunum and colon, but the values were
      significantly lower than ileum absorption parameters, with significant
      differences (P<0.05). There was no significant effect of verapamil on intestinal
      absorption of poncidin. The results showed that poncidin could be absorbed at all
      the studied intestinal segments while ileum seemed to be the best absorption
      segment in the concentration range of 10-1 000 MUg.L-1. The absorption was
      characterized by a linear dynamic process of passive transport, without
      absorption saturation. Weak acid environment was helpful for the intestinal
      absorption of poncidin, and ponicidin was not a substrate of P-glycoprotein (P
      gp).

PMID- 30200718
TI  - [Analysis of professor Lin Yi's experience for metastasis breast cancer by data
      mining].
AB  - Data mining method based on the traditional Chinese medicine(TCM) inheritance
      system(V2.5) was adopted to analyze professor Lin Yi's experience for metastasis
      breast cancer(MBC) by analysing the high frequency medicine, drug categories,drug
      properties,the key symptoms and key drugs of different metastasis regions and
      different syndromes, drug symptom analysis in the effective prescriptions for
      treating MBC by Lin from January 2013 to December 2017. A total of 89 MBC
      patients, 5 syndromes and 117 prescriptions were involved. The first 10 most
      frequently used were Atractylodis Macrocephalae Rhizoma, Poria, Dioscoreae
      Rhizoma, Coicis Semen, Crataegi Fructus, Hordei Fructus Germinatus, Galli Gigerii
      Endothelium Corneum, Hedyotis Diffusa, Codonopsis Radix, Astragali Radix. The
      warm and placid property was higher, the most herbs had Gan taste, the first two
      channel tropisms were spleen and the stomach. Drug symptom analysis in 5
      different metastasis regions and 6 different syndromes were also been done. The
      conclusion showed that professor Lin's experience as: recognizing the basis of
      diseases,differentiating the syndrome, combinating disease and syndrome,
      cautiously grasping pathogenesis,combinating tonification and purgation together,
      regulating balance, treating the symptoms and origin, regulating spleen and
      stomach, caring for the postnatal throughout, prefering ancient
      prescription,rational compatibility, using medicine gently.

PMID- 30200719
TI  - [Risk factors analysis and security application discussion of Polygonum
      multiflorum based on retrospective study].
AB  - In recent years,hepatotoxicity problem of Polygonum multiflorum has caused high
      attention. Domestic scholars also explored the causes of liver damage caused by
      it. For example, the establishment of guideline for diagnosis and treatment of
      herb-induced liver injury, and the theory about relationship between hepatocyte
      toxicity and chemical composition, solvents, processing, use and pathological
      basis of patients and so on. To try to combine theory with practice,author
      analyzed risk factors about the case reports of P. multiflorum causing liver
      damage, and made some suggestions on P. multiflorum about individualized
      application, drug selection and requirements for taking. This for providing
      reference for the safe use of P. multiflorum.

PMID- 30200720
TI  - [Technical specification for re-evaluation of post-marketing clinical
      effectiveness of traditional Chinese medicine (first draft)].
AB  - The post-marketing re-evaluation of traditional Chinese medicine (TCM) is a
      crucial stage for drug evaluation. Due to the particularity of TCM, it is
      necessary to re-evaluate the effectiveness of certain Chinese medicines by
      studying and collecting the studies on safety of long-term/extensive populations
      under actual clinical application, in order to verify the effectiveness of post
      marketing TCM. However, there is an absence in technical specifications for
      relevant clinical trials on re-evaluation of effectiveness at present. As a
      consequence, the preliminary technical specifications were drafted in this
      article, focusing on several perspectives related to the re-evaluation of post
      marketing clinical effectiveness of TCM, including ethical protection, research
      plan formulation, real-world research methods, randomized controlled trial
      methods, research methods of clinical pharmacological mechanism, sublimation
      method of TCM theory and so on. The objective of writing this article is to
      provide general methodological guidance for the re-evaluation of TCM post
      marketing effectiveness, so that the process and results of post-marketing re
      evaluation of TCM can be more scientific and reasonable.

PMID- 30200721
TI  - [Comparison of volatile components in Schisandra propinqua from different
      habitats by HS-SPME-GC-MS].
AB  - A headspace solid-phase microextraction gas chromatography-mass spectrometry (HS
      SPME-GC-MS) method was developed and optimized for qualitative and semi
      quantitative analysis of volatile components from Schisandra propinqua, a kind of
      Yi Nationality herb medicine. This method was used for analysis and evaluation of
      volatile components from S.propinqua from four different geometrical origins
      (Yunnan Wuding, Yunnan Luoping, Guizhou Qingzhen and Hubei Shennongjia). 51, 53,
      52, 50 compounds were identified from the above four kinds of samples
      respectively, in which 46 volatile components were contained in all of these four
      origins. The volatile components in these samples from different geographical
      origins were then compared by using principal component analysis, cluster
      analysis and other chemometrics methods. The results suggested that the analysis
      of volatile components can be used to distinguish the S.propinqua from four
      origins, and those samples from close geographical origins were more similar in
      volatile components. The developed method was stable, reliable, and suitable for
      rapid analysis of volatile components from S.propinqua, providing reference for
      quality control, drug development and scientific utilization of the herb.

PMID- 30200722
TI  - [Discussion on assessment method of Chinese medicine resources].
AB  - At the end of 2017, the former China Food and Drug Administration promulgated "
      the Guiding Principles for the Assessment of Chinese Medicine Resources" whose
      purpose is establishing the concept of " the production of Chinese traditional
      medicines, herbal pieces and etc. should be based on the premise of ensuring the
      production and quality of Chinese medicine resources" for a licensed holder of a
      drug listing or a production enterprise of Chinese Medicine by assessing this
      work through the resources of Chinese Medicine which finally achieves the
      strategic significance of promoting the sustainable utilization of Chinese
      medicine resources. Under the guidance of the overall idea of "the total amount
      is not reduced and the supply is guaranteed", this paper focuses on the following
      two methods of assessment: 1"family property assessment" of Chinese medicine
      resources based on "fixed total amount". 2 "Supply and demand balance assessment"
      of Chinese medicine resources based on "supply guarantee". In this paper, we
      discuss the difference and relationship between the national survey of Chinese
      medicine resources and the assessment of Chinese medicine resources. Finally, we
      put forward a basic strategy called" supply and demand balance assessment" of
      Chinese medicine resources based on "supply guarantee" that will guide the
      Industrial production of traditional Chinese medicine.

PMID- 30200723
TI  - [New method for evaluating pharmacodynamics of traditional Chinese medicine
      compounds based on its moderate regulation and principle of balanced adjustment
      of immunity under pan-immunomic].
AB  - For the basic research on the traditional Chinese medicine(TCM), objective
      syndrome of traditional Chinese medicine and evaluation criteria of traditional
      Chinese medicine compounds are hardly to break though. While, the modern
      immunology points out that the body is a counterbalance state and immune
      imbalance is the root of sickness. The thinking mode of treating diseases in
      traditional Chinese medicine is also "balance", considering disease is the result
      of bias which present the imbalance of "Yin counters Yang", "exterior counters
      interior", "cold counters heat" and "weak counters strong". The Chinese herbal
      compound formula preparation was applied on disease therapy based on theory of
      Chinese medicine, which was confirmed by long period clinical application. It is
      composed of multi-compounds and has the characteristic of multi-targeting.
      Integrative medicine has spawned pan-immunomics, and the evaluation of immune
      function (immune balance) has become an important basis for diagnosis and
      treatment models of integrative medicine. In addition, balance is the core idea
      of whole-systemic conception of traditional Chinese medicine. Therefore, we
      speculate that immune balance under pan-immunomic can bridge the traditional
      Chinese medicine and modern integrative medicine and is the important basis for
      objective syndrome of traditional Chinese medicine and evaluation criteria of
      traditional Chinese medicine compounds. According to the bridging theory, we
      attempt to utilize informatics and statistical methods to construct an evaluation
      system for pharmacodynamics of traditional Chinese medicine based on its moderate
      regulation and the balanced adjustment of immunity under pan-immunomic, which
      further reveal the scientific essence of the whole-systemic view of traditional
      Chinese medicine. This research brings out a new valuable strategy and provides a
      theoretical basis for accelerating the transformation of traditional Chinese
      medicine, especially the exploitation of Chinese herbal compound formula, and
      constructing the new drug innovation and review system for traditional Chinese
      medicine. Besides as a reference for traditional Chinese medicine objective
      syndrome and pharmacodynamics of traditional Chinese medicine compounds, the
      evaluation system can screen the immunity of sub-health population also. With the
      continuous accumulation of clinical sample and data, the evaluation system will
      be more accurate and intelligent.

PMID- 30200724
TI  - [Effect of traditional Chinese medicine in inhibiting obesity and inflammatory
      diseases by regulating gut microbiota].
AB  - Traditional Chinese medicine(TCM) has been increasingly used in the prevention
      and treatment of obesity and obesity-related diseases. However, its mechanism of
      action is not yet clear. In recent years, with the development of high-throughput
      sequencing technology, scientific researches have found that the disorder of gut
      microbiota is associated with obesity and other diseases. Furthermore, it has
      been found that TCM can improve the structure of gut microbiota by increasing
      probiotics and reducing pathogens, which play an importent role in preventing the
      development and progression of obesity and other diseases. This article first
      explores the possible association between intestinal microbiota and obesity.
      Then, it reviews the traditional Chinese medicine and its role in regulating
      intestinal microbiota for the prevention and treatment of diseases, including
      obesity and inflammation, insulin resistance, type 2 diabetes, non-alcoholic
      fatty liver disease, inflammatory bowel disease and other diseases, in
      theexpectation of new strategies and research direction for treating obesity and
      relevant diseases, and providing important guidance for further studies in this
      field in the future.

PMID- 30200725
TI  - [Rapid identification of geographical origins and determination of
      polysaccharides contents in Ganoderma lucidum based on near infrared spectroscopy
      and chemometrics].
AB  - Near infrared spectroscopy combined with chemometrics methods was used to
      distinguish Ganoderma lucidum samples collected from different origins, and a
      prediction model was established for rapid determine polysaccharides contents in
      these samples. The classification accuracy for training dataset was 96.87%, while
      for independent dataset was 93.33%; as for the prediction model, 5-fold cross
      validation was used to optimize the parameters, and different signal processing
      methods were also optimized to improve the prediction ability of the model. The
      best square of correlation coefficients for training dataset was 0.965 4, and
      0.851 6 for validation dataset; while the root-mean-square deviation values for
      training dataset and validation dataset were 0.018 5 and 0.023 6, respectively.
      These results showed that combining near infrared spectroscopy with suitable
      chemometrics approaches could accuracy distinguish different origins of G.
      lucidum samples; the established prediction model could precious predict
      polysaccharides contents, the proposed method can help determine the activity
      compounds and quality evaluation of G. lucidum.

PMID- 30200726
TI  - [Research on morphological characteristics change of quercetin and polyphenols of
      accumulation dynamic of spines of Gleditsia sinensis].
AB  - To study morphological characteristics change of the development process and
      quercetin and polyphenols of accumulation dynamic of the spines of Gleditsia
      sinensis, measure and compare morphological indexes using Vernier caliper, ruler
      and balance, calibrate and analysis quercetin and polyphenols content using HPLC
      and colorimetric method. The spines of G. sinensis development process is divided
      into formation period (the beginning of August to the beginning of November),
      dormant period (the beginning of November to the end of March in the following
      year), germination period (the end of March to the middle of April), fast growth
      period (the middle of April to the middle of August), browning period (the middle
      of August to the end of August) and mature period (the beginning of September to
      the end of December). Formation period the spines primordium divides and forms
      the scale bubs; dormant period the scale bubs are in a dormant state; germination
      period the bubs scales fall off, spines primordium began to development; fast
      growth period rapid growth to maximum; browning period browning from the tip and
      browns until the whole becomes brown; mature period The early stage of maturity
      is full of luster, gradually the color deepened and the luster faded. The
      accumulation of quercetin was gradually decreasing after increasing. The total
      polyphenol accumulation was significantly decreased and then gradually increased,
      decreased finally. The content of quercetin was increased from 0.000 4%-0.002 6%,
      and the polyphenol content decreased from 0.761 9%-0.049 1% and then slowly
      increased to 0.286 9% in the fast growth period.The quercetin continuous increase
      to 0.004 3% and total polyphenol increased to 0.421 6% in the browning period. In
      the mature period, the quercetin content significantly decreased after reaching
      0.009 6% in September, and the polyphenols content decreased after reaching 0.723
      5% in October. Using principal component analysis results: September first,
      October 2nd, November 3rd. The morphological characteristics change of the
      development process and quercetin and polyphenols accumulation were determined.
      The development process is divided into six periods, the best harvest time is the
      early stage of mature period. Provide theoretical support for the utilization of
      the spines of G. sinensis and cultivation techniques of high yield.

PMID- 30200727
TI  - [Cloning and expression analysis of squalene epoxidase genes from Siraitia
      grosvenorii].
AB  - Siraitia grosvenorii, vine plant of Cucurbitaceae family, has been used as
      natural sweetener and folk medicine. The major components and sweet substances
      are both known as mogrosides which are cucurbitane-type tetra-triterpenoids.
      Squalene epoxidase (SQE) has been generally recognized as the common rate
      limiting enzyme in triterpenes and phytosterols, catalyzing into their common
      precursor 2,3-oxidosqualene (OS); however, in the biosynthesis of mogrosides, the
      precursor was 2,3,22,23-dioxidosqualene (DOS) instead of OS. To explore the
      specific SQE in S. grosvenorii, we cloned two full-length SQEs (SgSQE1, SgSQE2),
      performed bioinformatic analysis, analyzed the expression patterns in different
      periods of fruits by Real-time PCR, and induced the prokaryotic expressions.
      Finally, the interactive sites between SQE and substrate were predicted by
      docking, which would provide evidence for SQE gene function study of mogrosides
      and also lay foundation for triterpene biosynthesis in other plants. SgSQE1 and
      SgSQE2 both encoded predicted proteins of 524 amino acids, and shared 84%
      identity to each other at residues level, but had high specificity at N-terminal
      region. They both accumulated in fruits, but with different patterns, SgSQE1
      increased rapidly and reached the highest level at 15 d, which had identical co
      expression pattern with cucurbitadienol synthase (CS). SgSQE2 had a relatively
      constant level. The docking results showed that predicted proteins of SgSQE1 and
      SgSQE2 can interact with OS, with different contact sites (R348 for SgSQE1, H349
      for SgSQE2). The recombinant proteins had no activities by prokaryotic
      expression, which were caused by transmembrane regions. However, all the results
      strongly suggested that SgSQEs were both involved in secondary metabolites
      biosynthesis in S. grosvenorii. SgSQE1 might be involved in mogrosides
      biosynthesis and SgSQE2 might participate in other cucurbitane-type triterpenes
      or phytosterols biosynthesis.

PMID- 30200728
TI  - [Quality characterization analysis of single decoction and merger decoction of
      Baihu and Guizhi].
AB  - To study the differences and similarities in pharmaceutical characterization and
      pharmacodynamic characterization between the single decoction and merger
      decoction of Baihu and Guizhi. The same technology parameters were used to
      prepare Baihu and Guizhi single decoticon and merger decoction extracts, and then
      the differences and similarities in pharmaceutical characterization were analyzed
      based on their HPLC fingerprint, content of index components, and the extraction
      content. The pharmacodynamic differences and similarities were analyzed by
      inflammatory model and pain model. There was no significant difference in HPLC
      chromatographic peak, but the peak area value reflected the difference of
      quantity to some extent. It was found that the peak value of single Rhizoma
      anemarrhenae and Cassia twig decoction was less than the peak of their merger
      decoction, but the peak value of single honey-fried Licorice root decoction was
      greater than the peak of merger decoction. The contents of neomangiferin,
      mangiferin and timosaponin B II among index components as well as extraction
      content in merger decoction were higher than those in single decoction. The
      contents of liquiritin and glycyrrhizic acid as well as extraction content in
      merger decoction were lower than those in single decoction. There was no
      significant difference in the content of cinnamicacid and its extraction content
      between merger decoction and single decoction. According to the efficacy
      experiment, both of them showed significant anti-inflammatory and analgesic
      effects. However, the merger decoction showed faster anti-inflammation effect,
      and longer analgesic effect. It can be concluded that the merger decoction and
      single decoction of Baihu and Guizhi have the same material basis, and the merger
      decoction is better for the dissolution of the active ingredients in this recipe,
      and is more beneficial to the therapeutic effect.

PMID- 30200729
TI  - [System modeling on Chinese herbal medicine process based on multi-block partial
      least squares].
AB  - The system model of Chinese herbal medicine process is the basis for improving
      the precision of pharmaceutical process and ensuring the stable transmission of
      quality between different sections of the process. By taking the wet granulation
      tableting process as the research object and using the Panax notoginsengs sapions
      (PNS) as a model drug, multi-block partial least squares method (MBPLS) was used
      in this article to build the system model of Chinese herbal medicine process,
      analyze the mass transmission rules in the process and improve the understanding
      on pharmaceutical process system of Chinese medicine. According to the process
      flow, the quality attributes of raw materials, granules and tablets collected in
      the process were divided into different data blocks, and the MBPLS method was
      used to establish system model. The R2Y and Q2Y of MBPLS model were 89.1% and
      65.5%, respectively, indicating that the performance of the MBPLS model was good.
      By analyzing the parameters of MBPLS model, it was determined that the physical
      quality attributes of PNS raw materials and quality attributes of PNS granules
      were the key factors to affect the quality of PNS tablets. The particle size,
      bulk density and tapped density of PNS raw materials were the critical quality
      attributes which caused the quality variations of PNS granules and PNS tablets.
      MBPLS can quantify the contributions of each unit to the product quality by
      dividing the quality attributes into different units. It was helpful to analyze
      the interactions between the process units of Chinese herbal medicine and it
      could be applied to build system model of other Chinese herbal preparations
      processes.

PMID- 30200731
TI  - [Effect of different initial processing methods on quality of gardenia].
AB  - To investigate the effect of different initial processing methods on the quality
      of Gardenia and determine the best cooking time in gardenia processing through
      the determination of index components content. The contents of geniposide,
      crocetin I and total iridoid glycosides in Gardenia were determined before
      storage, six months after storage and one year after storage. During storage, the
      contents of geniposide, crocetin I and total iridoid glycosides in directly dried
      Gardenia were 1.68%, 0.45% and 6.45% respectively. The contents of geniposide,
      crocetin I and total iridoid glycosides in Gardenia with different steaming time
      were 1.34%-0.5%, 0.28%-0.06% and 6.09%-1.59% respectively. The contents of
      geniposide, crocetin I and total iridoid glycosides in Gardenia with different
      boiling time (adding alum)were 1.42%-0.41%, 0.35%-0.07% and 6.40%-1.65%
      respectively. The direct drying of Gardenia samples could not achieve the
      function of killing enzyme and protecting glycosides. The enzymes from
      degradation of the index components were basically destroyed after steaming time
      of 13 min or boiling (adding alum) time of 8 min, achieving the function of
      killing enzyme and protecting glycosides.

PMID- 30200732
TI  - [Lithagogue effects of Pyrrosia lingua from Guizhou province on experimental
      renal calculus in rats].
AB  - To screen the active fractions with lithagogue effects of Pyrrosia lingua from
      Guizhou province and preliminarily investigate its mechanism. The rats were fed
      with 1% ethylene glycol and 2% ammonium chloride to establish the nephrolithiasis
      models, which were used to evaluate thelithagogue effects of different polar
      fractions of P. lingua from Guizhou province. The level of urinary calcium and
      oxalic acid in urine, renal calcium, oxalic acid, superoxide dismutase (SOD),
      catalase(CAT) and malondialdehyde (MDA) in renal tissues,as well as crystalline
      deposit and lithogenesis in renal tissues and the levels of creatinine(Cr) and
      blood urea nitrogen (BUN) in the serum were detected. The effective compounds
      were inferred from the analysis of active fractions extract based on LC-MS
      technology. Petroleum ether fraction and dichloromethane fraction of P. lingua
      from Guizhou province can reduce renal oxalic acid and renal calcium
      concentration, increase urinary oxalic acid and urine calcium, with significant
      inhibitory effect on the formation of renal calculus in rats, significantly
      increase SOD and CAT activities in renal tissues, and significantly reduce MDA
      levels. LC-MS analysis showed that the caffeine, citric acid and tartaric acid
      among the compounds from petroleum ether fraction and dichloromethane fraction
      had lithagogue effects. Both the petroleum ether fraction and dichloromethane
      fraction of P. lingua from Guizhou province showed good effect on prevention and
      treatment of calculus in middle dose groups, and the mechanism may be associated
      with antioxidation, reducing calcium oxalate crystal deposition, and promoting
      calcium oxalatecrystal release, in addition, caffeine, citric acid and tartaric
      acid had lithagogue effects.

PMID- 30200730
TI  - [Quality control of Dandeng Tongnao Ruanjiaonang based on UPLC fingerprint
      combined with chemical pattern recognition].
AB  - To establish the ultra performance liquid chromatography (UPLC) fingerprint of
      Dandeng Tongnao Ruanjiaonang and conduct a systemic, comprehensive quality
      evaluation of the drug by combining with a chemical pattern recognition method.
      In this study, Waters UPLC ultra-high performance liquid chromatography
      instrument and ACQUITY UPLC?HSS T3 chromatographic colum n were employed to
      perform the separation with acetonitrile-0.1% formic acid aqueous solution as the
      mobile phase for gradient elution; and the detection wavelength was set at 256 nm
      to establish the UPLC fingerprint of 10 batches of Dandeng Tongnao Ruanjiaonang.
      Then, the further quality assessment of the drug was carried out by similarity
      evaluation, Cluster Analysis(CA), Principal Component Analysis (PCA) and
      orthogonal partial least squares discriminant analysis (OPLS-DA). Finally, 77
      peaks were recognised as common peaks in the fingerprint, and 15 peaks of them
      were identified using standard references. The similarity value of these 10
      batches of drugs was all above 0.960, indicating a relatively stable quality. But
      minor differences were still discovered between the batches of the drug by CA and
      PCA. Finally, 6 common peaks were recognised as the quality makers using OPLS-DA
      method. The analysis method established in this study was scientific, accurate,
      reliable and simple; fingerprint combined with chemical pattern recognition
      technique can be used to systematically and comprehensively evaluate the drug
      quality of Dandeng Tongnao Ruanjiaonang; what's more, it could also provide a
      reference for the quality control of traditional Chinese medicine and its
      preparations at the same time.

PMID- 30200733
TI  - [Secondary metabolites of Streptomyces sp. A1693].
AB  - By means of various chromatographic methods such as Sephadex LH-20,ODS,and semi
      preparative HPLC,ten compounds were isolated from Streptomyces sp. A1693 and
      their structures were elucidated on the basis of spectroscopic data and physico
      chemical methods. The compounds comprised 5 butenolides,2 diketopiperazines,and 3
      antimycin antibiotics. The structures were identified as (5S)-5-(11
      hydroxymethyloctyl)furan-2(5H)-one (1), (5S)-5-(11-hydroxy-11-methylheptyl)furan
      2(5H)-one (2), (5S)-5-(11-methyl-12-oxooctyl) furan-2(5H)-one (3), (5S)-5-(11
      hydroxy-11-methyloctyl)furan-2(5H)-one (4), (5S)-5-(11-hydroxy-12
      methyloctyl)furan-2(5H)-one(5),cyclo-Phe-Val (6),cyclo-Phe-Ile (7),uranchimycin A
      (8),uranchimycin B (9),and deisovalerylblastomycin (10). Among them,1 was defined
      as a new compound. All the compounds didn't show the cytotoxic activity against
      A549 cell line (IC50>50 mg.L-1).

PMID- 30200734
TI  - [Chemical constituents from fruits of Aristolochia mollissima and their
      nematicidal activity against root-knot nematode].
AB  - In the present study, in vitro nematicidal activity of chemical compositions from
      the methanol extract of Aristolochia mollissima fruits against the second stage
      juvenile (J2) of Meloidogyne javanica have been investigated. By using silica gel
      column chromatography, Sephadex LH-20 gel column chromatography methods, fourteen
      compounds were isolated from methanol extract of A. mollissima fruits. On the
      basis of spectral data, their structures were identified as aristolochic acid I
      (1), aristololactam I (2), aristololactam W (3), manshurolide (4), aristolactone
      (5), saropeptate (6), 2-(1-oxononadecyl)aminobenzoic acid (7), beta-sitosterol
      (8), sitostanetriol (9), daucosterol (10), formosolic acid (11), 5-ethyl-8,8
      dimethyl nonanal (12), tetracosanoic acid,2,3-dihydroxypropyl ester (13) and
      tetracosanoic acid (14), respectively. It is the first time that compounds 2-4, 6
      7, 9-14 are separated from A. mollissima. Furthermore, nematicidal activity of
      fourteen monomer compounds against J2 Meloidogyne javanica in vitro were
      analyzed. The compounds 1-3, 6-7 exhibited different degrees toxic effects on J2
      M. javanica in vitro, especially for aristolochic acid I (1), aristololactam I
      (2), aristololactam W (3) with the LC50 values of 45.25, 36.56, 119.46 mg.L-1
      after 96 h. So, A. mollissima have the potential value of developing new plant
      source to control root nematodes.

PMID- 30200735
TI  - [Study on structural conversion of dihydrochelerythrine in different solvents].
AB  - Dihydrochelerythrine was isolated from the ethanol extract of Corydalis yanhusuo
      by chromatographic and recrystallization techniques. To our knowledge, this is
      the first report that dihydrochelerythrine was found to be unstable. The NMR,
      HPLC, and LC-MS were applied to monitor the structural conversion process of
      dihydrochelerythrine. The results showed that when dissolved in polar deuteration
      solvent (e.g., DMSO-d6 & MeOD), dihydrochelerythrine is directly converted to
      chelerythrine gradually. However, if used non-polar reagent (e.g.,CD2Cl2), the
      sample of dihydrochelerythrine undergoes the formation of pseudobase,
      chelerythrine, and bimolecular ether then followed by oxidation to
      oxychelerythrine as the major final product. Which leads to this phenomenon maybe
      is that the C-6 in dihydrochelerythrine is highly reactive to nucleophiles, and
      is easily converted to different derivatives in different solvents attributed to
      the solvent effect. This finding will contribute to the extraction and isolation,
      bioactivity screening, and quality evaluation of medicinal materials containing
      dihydrochelerythrine and other similar derivatives.

PMID- 30200736
TI  - [Quality evaluation of Desmodium styracifolium by fingerprint, pattern
      recognition combined with quantitative analysis of multi-components by single
      marker].
AB  - HPLC analysis was performed on a Phenomenex PS C18(4.6 mm*250 mm, 5 MUm)column
      using methanol -0.2% formic acid (30:70) at a flow rate of 0.8 mL.min-1. The
      column temperature was 30  degrees C and the detection wavelength was set at 335
      nm. The injection volume was 10 MUL. The HPLC fingerprint of Desmodium
      styracifolium was established with 10 common peaks, and 5 of them were identified
      as vicenin-1, schaftoside, isoorientin, isoschaftoside and isovitexin,
      respecivetly. The fingerprints of 21 batches of D. styracifolium samples were
      analyzed with similarity evaluation, cluster analysis, principal component
      analysis and partial least squares discriminant analysis. There was no
      significant difference among the quantitative results of these five ingredients
      verified by external standard method (ESM) and quantitative analysis of multi
      components by single marker (QAMS) method. The application of fingerprint,
      pattern recognition combined with QAMS can provide more comprehensive references
      for the quality control and evaluation of D. styracifolium.

PMID- 30200737
TI  - [Comparison on proteins of Saigae Tataricae Cornu and Caprae Hircus Cornu].
AB  - SDS-PAGE and LC-MS/MS were used to identify proteins in Saigae Tataricae Cornu
      (SAH) and Caprae Hircus Cornu (GH). Trypsin digestion peptides from SAH and GH
      were obtained by in-gel digestion, after which nano LC-LTQ/Orbitrap MS was used
      to identify the proteins in SAH and GH. As a result, in total 101 proteins and
      140 proteins were identified form SAH and GH, respectively. There were 43
      keratins (KRTs) and keratin-associated proteins (KAPs) identified, which account
      for 42.6% of the 101 proteins in SAH. The proportion of KRTs and KAPs in GH was
      37.1%. The comparison between SAH and GH showed that the main common components
      in SAH and GH were structural molecule activity proteins, such as KRTs and KAPs.
      In the present study, we provide determination method and experimental data for
      investigating the material basis of SAH and GH, guiding the investigation on
      effective material basis and quality standard of animal horn derived TCMs.

PMID- 30200738
TI  - [Effect of rosmarinic acid from Sarcandra glabra in inhibiting proliferation and
      migration and inducing apoptosis of MDA-MB-231 cells via regulation of
      expressions of Bcl-2 and Bax].
AB  - Rosmarinic acid is one of anti-tumor ingredients in the Sarcandra glabra. After
      treatment with 0, 10, 30, 90, 270 and 810 MUmol.L-1 rosmarinic acid for 24, 48,
      72 hours respectively, the inhibitory effects on MCF-7 and MDA-MB-231 cells were
      observed by CCK-8 and cell wound healing test. No significant inhibition effecton
      proliferation and migration was observed in MCF-7 cell. However, 90, 270 and 810
      MUmol.L-1 rosmarinic acid could inhibit the proliferation and migration of MDA-MB
      231 cells in a dose-dependent and time-dependent manner. Flow cytometry was
      further used to detect apoptosis ratios of MDA-MB-231 cells after Annexin V
      FITC/PI staining, and significant apoptosis was observed after rosmarinic acid
      treatment. Real-time PCR and Western blot tests were carried out to detect the
      expressions of apoptosis-related genes. The down-regulation of the Bcl-2
      expression and the up-regulation of the Bax expression were observed in MDA-MB
      231 cells after rosmarinic acid treatment. The results suggested that
      rosmarinicacid can inhibit the proliferation and migration, and induce the
      apoptosis of MDA-MB-231 cells, which may be correlated with the down-regulation
      of Bcl-2 gene and the up-regulation of Bax gene.

PMID- 30200739
TI  - [Effects of sleep deprivation induced blood stasis syndrome on platelet
      activation in rats].
AB  - Blood stasis syndrome is the pre-state of thrombotic disease. The model of blood
      stasis syndrome in rats was induced by sleep deprivation to study on effects of
      blood stasis syndrome on platelet activation. The weight, the color of tongue and
      hemorheology for the blood stasis syndrome of Chinese medicine were measured
      after modeling. The release of platelet granules and platelet activation factors
      in plasma were detected by ELISA kit related indicators to provide experimental
      basis for platelet function evaluation and related drug effects in syndrome
      research. The results showed that the weight of the model group rats was
      significantly lower than that of the normal group (P<0.01). The tongue showed a
      dark purple blood stasis pattern, and the R, G and B values of the tongue surface
      in model group were significantly lower than those of the normal group (P<0.01).
      The hemorheological parameters including high shear, middle shear and low shear
      viscosity in whole blood were significantly higher than those in the normal group
      (P<0.01). But plasma viscosity did not change significantly. The release levels
      of platelet alpha particles (GMP-140, beta-TG, PF4) and dense particles (ADP, 5
      HT) were significantly higher than those in the normal group (P<0.01). The levels
      of TXB2 and 6-keto-PGF1alpha in plasma were significantly higher than those in
      the normal group (P<0.01). The ratios of TXB2 and 6-keto-PGF2alpha were also
      significantly higher than those in the normal group (P<0.01). The levels of PAF
      in plasma in model group were significantly higher than those in the normal group
      (P<0.01). It was concluded that platelet functions could be changed induced by
      sleep deprivationin rats with blood stasis syndrome, and there might be
      inflammation and endothelial cell dysfunction.

PMID- 30200740
TI  - [Effects of GBE50 on LPS/ATP induced NLRP3 inflammasome activation in primary rat
      microglia].
AB  - In this study, the anti-inflammatory mechanism of Ginkgo biloba extract 50
      (GBE50) and its mechanism of action on NLRP3 inflammatory corpuscles were
      observed by primary microglia cells. LPS/ATP was used to stimulate microglia, and
      the best time for stimulation and optimal concentration of GBE50 were screened.
      Pro-inflammatory cytokine IL-1beta and TNF-alpha was determined by ELISA. Western
      blot was performed to observe the protein expression of NLRP3, ASC, caspase-1 and
      IL-1beta in cultured primary rat microglia. Effect of GBE50 on NLRP3 inflammatory
      corpuscle aggregation was detected by CO-IP. GBE50 (10 mg.L-1) preconditioning
      could significantly inhibit the expression of LPS (100 MUg.L-1,12 h), ATP (5
      mmol.L-1, 30 min) induced primary microglia corpuscle associated protein,
      inflammatory corpuscle aggregation, and the release of inflammatory factors IL-6
      and TNF-alpha. These results indicated that GBE50 could inhibit the secretion of
      inflammatory factors after microglia activation, which is related to down
      regulating the protein expression and activity of NLRP3 inflammatory corpuscle.

PMID- 30200741
TI  - [Network pharmacology of flavonoids in Sophora alopecuroides].
AB  - The aim of this paper was to investigate the potential pharmacological effect of
      flavonoids in Sophora alopecuroides by network pharmacology. This study predicted
      the potential targets of 11 flavonoids of S. alopecuroides with help of reversed
      pharmacophore matching target recognition service platform (PharmMapper). The
      pathway information was acquired from DAVID and KEGG databases. Cytoscape
      software was used to construct the "ingredient-target-pathway" network of
      flavonoids active components of S. alopecuroides. The flavonoids active
      components of S. alopecuroides play anti-inflammatory, blood sugar regulating and
      other pharmacological effects by regulating 62 targets (such as INSR,KDR,MET) and
      intervening 44 pathways, such as B cell receptor signaling pathway, insulin
      signaling pathway, neurotrophin signaling pathway, and T cell receptor signaling
      pathway. In this study, the mechanism of "muti components-multitargets-multiple
      pathway" of flavonoids was studied. It reflects the multi-components, multi
      targets and multiple pathway features of traditional Chinese medicine. Meanwhile,
      it provides a scientific basis for the elucidation the mechanism of S.
      alopecuroides as a medicine, and the development and utilization resources of S.
      alopecuroides.

PMID- 30200742
TI  - [Molecular mechanism of Shaofu Zhuyu decoction in treating endometriosis
      dysmenorrhea based on GPER2/MAPK/STAT1 axis].
AB  - The aim of this paper is to study the molecular mechanism of Shaofu Zhuyu
      decoction in treating dysmenorrhea of endometriosis based on GPER2/MAPK/STAT1
      axis. In this study, HE staining was used to observe the pathological changes of
      the rats in each group. The levels of TNF-alpha and IL-6 were detected by ELISA
      assay. The mRNA expressions of neurotransmitter receptor (NK1) and GPER were
      detected by qPCR. The protein contents of MAPK and STAT1 were detected by Western
      blot. According to the results, compared with the model group, Shaofu Zhuyu
      decoction could significantly improve the inflammation of the ectopic uterine
      cavity tissue, decrease the contents of TNF-alpha and IL-6 in the uterine cavity,
      the mRNA expressions of NK1 and GPER, and the protein expressions of MAPK and
      STAT1. In conclusion, Shaofu Zhuyu decoction could effectively inhibit the
      expressions of GPER2, MAPK and STAT1, decrease the levels of TNF-alpha, IL-6 and
      NK1 mRNA and relieve the inflammatory pain in patients with endometriosis.

PMID- 30200743
TI  - [Analysis on medication regularity and action mechanism of Tibetan medicine in
      treatment of spleen and stomach diseases based on data mining and integrated
      pharmacology].
AB  - To explore the medication regularity of Tibetan medicine in the treatment of
      spleen and stomach diseases, analyze the potential drug targets and interactions
      of the prescriptions, and reveal the mechanism of Tibetan medicine in the
      treatment of spleen and stomach diseases. The prescriptions in Tibetan medicine
      for treatment of spleen and stomach diseases were collected, and Traditional
      Chinese Medicine Inheritance Support System (TCMISS) was used to analyze the
      association rules between the herbs and discover the core herbs and new
      prescriptions. The integrated pharmacology platform V1.0 software was used to
      construct "herb-compound-target" network and investigate the interactions between
      various herbs and related pathways of Tibetan medicine Wuwei Shiliu powder in the
      treatment of spleen and stomach diseases. Among the 216 prescriptions of Tibetan
      medicine in the treatment of spleen and stomach diseases, pomegranate seed was
      used at a highest frequency (118 times), followed by white cardamom (107 times)
      and comatose (107 times). 12 new prescriptions were evolved by using the
      association rules (support>=34%, confidence>=0.85). 5 242 related drug targets
      and 20 related pathways were obtained from classic formula Wuwei Shiliu Powder
      (FDR<0.01). It was proposed that Tibetan medicine treatment for spleen and
      stomach diseases was mainly based on proliferation of "stomach fire" and the main
      drugs were for regulating Qi-flowing for strengthening spleen. The mechanism may
      be associated with regulation of digestive juice secretion, proton pump,
      mitochondria, regulation of intestinal digestion and immunity, the body's
      immunity to microorganisms function and other multiple targets and pathways to
      achieve the joint intervention.

PMID- 30200744
TI  - [Analysis on medication rules for treatment of dementia by ancient physicians
      based on data mining methods].
AB  - To analyze the medication features and regularity of prescriptions of Chinese
      medicine in treating patients with dementia based on ancient medical records. In
      the article, we retrieved the ancient medical records related to the treatment of
      dementia (from the Han Dynasty to the late Qing period) in Chinese Medical
      Classics, Chinese Ancient Medical Books and digital library, and then set up a
      medical records normalized database. The medication features and prescription
      rules for dementia were analyzed by frequency statistics and association rules
      (Apriori algorithm, improved mutual information algorithm and complex system
      entropy clustering). Finally, a total of 156 prescriptions were selected,
      involving 123 Chinese herbs, with a total frequency of 11 747 for the herbs, and
      8 core prescriptions were mined. After the association rules between the
      frequency and prescriptions for the treatment of dementia were determined, we
      found that the most commonly used herbs included Fuling (Poria), Yuanzhi
      (Polygalae Radix), Renshen (Ginseng Radix et Rhizoma), Shichangpu (Acori
      Tatarinowii Rhizoma), Gancao (Glycyrrhizae Radix et Rhizoma), Danggui (Angelicae
      Sinensis Radix), Maidong (Ophiopogonis Radix), Baizhu (Bletillae Rhizoma),
      Dihuang (Rehmanniae Radix) and Ganjiang (Zingiberis Rhizoma); the frequently-used
      drugs compatibility was mainly for tonifying Qi-blood, regulating Yin and Yang
      and inducing resuscitation. The drugs were mainly of warm nature and sweet (mild)
      flavor, and the channel tropism of drugs mainly distributed to the heart, liver,
      spleen and kidney. The core prescriptions were composed of Renshen (Ginseng Radix
      et Rhizoma), Fuling (Poria), Yuanzhi (Polygalae Radix), Shichangpu (Acori
      Tatarinowii Rhizoma), and Baizhu(Bletillae Rhizoma). In conclusion, high
      frequency herbs and core prescriptions reflect the prescriptions by ancient
      physicians mainly focus on Qi-replenishing, spleen-invigorating and heart
      nourishing, but also reflect the prescription rules of nourishing Yin, enriching
      blood, eliminating phlegm and warming Yang for the treatment of dementia. The
      medication features and prescription rules for the treatment of dementia obtained
      by association rules are useful to guide the clinical practice of Chinese
      medicine in treatment of dementia.

PMID- 30200745
TI  - [Treatment of ankylosing spondylitis with Zhengqing Fengtongning release tablets:
      Meta-analysis of randomized controlled trials].
AB  - The review aims to assess the effectiveness and safety of Zhengqing Fengtongning
      release tablets in treating ankylosing spondylitis (AS) systematically through
      searching relevant electronic databases and collecting relevant literature. Such
      Chinese databases as CNKI, VIP, Wanfang, and English databases as PubMed, EMbase
      and Cochrane Library, etc, were searched from the date of their establishment to
      September 2017. According to the inclusion and exclusion criteria, the
      methodology quality of included studies was evaluated by two independent reviewer
      using Cochrance evaluation system, and Meta-analysis on the clinical efficacy and
      safety of Zhengqing Fengtongning release tablets for AS was conducted with RevMan
      5.3 software. Seven randomized control trials (RCTs) including 570 patients of AS
      were included, with 294 patients in Zhengqing Fengtongning treatment group and
      276 patients in the western medicine control group. Meta-analysis showed that:
      Zhengqing Fengtongning alone treatment was superior to sulfasalazine groups in
      the effect on improving the total effective rate. Besides, as compared to
      sulfasalazine control group, the time of morning stiffness and the finger-to
      floor distance were significantly shortened in Zhengqing Fengtongning treatment
      group. However, the cciput-to-wall distance, the chest expansion, Schober's test,
      disease activity score (DAS) in patients, disease activity score (DAS) in
      doctors, ESR, CRP showed no statistically significant differences. As compared
      with western medicine control group, Zhengqing Fengtongning combined with western
      medicine had a higher total effective, significantly shorten the time of morning
      stiffness, and increase Schober's test values; However, the cciput-to-wall
      distance, the finger-to-floor distance, the chest expansion, DAS in patients, DAS
      in doctors, ESR and CRP showed no statistically significant differences.
      Zhengqing Fengtongning had less adverse reactions in clinical application, and
      the main adverse reaction was skin rash or itching when used alone. The study
      showed: Zhengqing Fengtongning is effective for AS with high safety, but high
      quality clinical trials are still needed to further prove its clinical efficacy
      and safety.

PMID- 30200746
TI  - [Clinical characteristics of Yinhua Miyanling Pian users based on real world
      study].
AB  - Clinical characteristics of Yinhua Miyanling Pian user group were analyzed based
      on real world hospital information system (HIS)database. The information was
      collected from the HIS in sixteen hospitals of grade III-A. Normalizing the data
      and descriptive analysis was performed. Among the 5 312 cases, female
      patients(63.67%) were more than male patients (36.33%). The median age was 49
      years old. The age of 18-65 accounted for 74.52%.The patient was admitted to the
      hospital's department of obstetrics and gynecology(28.71%) and urology(28.43%).
      The median single dose is 2 g, accounted for 49.55%. The median daily dose is 6
      g. 88.80% of patients were treated for less than 7 d. The median hospitalization
      were 12 d, most were 7-14 d accounted for 41.70%. Most hospitalization expenses
      payment by medicare, accounted for 80.22%. The median hospitalization expenses
      was 12 211.47 RMB. Most patients with benign tumor(27.36%) and malignant
      tumor(15.56%), next is the obstruction of urinary tract(15.49%) and urinary
      calculi(10.52%). The most common syndromes were damp heat syndrome(32.46%), liver
      and kidney deficiency syndrome(15.33%) and splenasthenic fluid-retention
      syndrome(15.01%). Clinical use is combined with antibiotics, as well as
      traditional Chinese medicine heat clearing agents, tonic drugs and so on.
      Finally, 44.22% were cured and 51.05% were better. Most of the drug users were
      adults, and mostly were female. Most with the tumor, urinary tract obstruction or
      stones. TCM syndrome is mainly characterized by dampness and heat, deficiency of
      liver and kidney, and dampness of spleen. In clinical practice, it was mainly
      combined with Western medicines, and Chinese medicines were also a-vailable. And
      most are combined with antibiotics.The medication basically conforms to the drug
      instruction. Based on the results of the real world HIS,Yinhua Miyanling Pian
      could provide theidea and reference for regulating the medication in adolescent
      patients.

PMID- 30200747
TI  - [Effect of dihydroartemisinin at low concentration on intervention of Plasmodium
      falciparum 3D7 strain].
AB  - Malaria is still the most severe strain of the human malaria parasites, and
      malaria disease is life-threatening which can result in severe anemia and
      cerebral malaria, especially in children in tropical Africa. Previous studies
      have shown that artemisinin and its derivatives could selectively kill
      erythrocytic stage of malaria and have a greater impact on the ring period. In
      recent years, there have been new findings of its mechanism continually. However,
      the concentration of artemisinin and its derivatives used in these studies can
      reach 50 to 80 times the half-inhibitory concentration in vitro. In this study,
      the international standard strain 3D7 of Plasmodium falciparum was used to
      culture in vitro. After half-inhibitory concentration of dihydroartemisinin was
      treated, the morphological changes of P. falciparum intraerythrocytic stage were
      observed, and then the 3D7 life cycle and effects of different developmental
      stages after dosing was explored. The 3D7 strain of P. falciparum was
      continuously synchronised more than 3 times. And dihydroartemisinin (DHA) at half
      maximal inhibitory concentration (10 nmol.L-1) was administered for 6 hours after
      the last synchronization, and 3 life cycles were continuously observed (132 h).
      The results showed that compared with the parasites untreated by DHA, there was a
      noticeable delay in the life cycle of at least 36 h, indicating that the growth
      of 3D7 was significantly inhibited by DHA (P<0.001), and the rate of ring
      formation was significantly reduced (P<0.05). The trophozoites were abnormal in
      shape, such as shrink in size, and the number of merozoites in schizonts was
      significantly decreased (P<0.05). These results suggested that non-killing
      concentrations of DHA (meaning parasites can be inhibited but not killed) can
      significantly inhibit the growth of P. falciparum, which may not only affect the
      ring stage, but also have an impact on other stages of the P. falciparum.

PMID- 30200748
TI  - [Varieties textual research on "Bangjian": traditional Tibetan medicine including
      blue, black and variegated flowers].
AB  - "Bangjian" were traditional Tibetan medicine-flowers from Gentianaceae, which
      were widely used and had a long medicinal history for the function of
      detoxifying, curing heat symptoms and treating the laryngitis. The Tibetan
      compound preparation endowed SFDA approval number always used Bangjian aas the
      main raw materials for relieving cough, asthma and treating respiratory diseases
      such as acute and chronic bronchitis. Its commodity medicinal materials were also
      sold in Qinghai, Sichuan, Tibet and other local medicinal materials market and
      local specialty marke. However, when recorded by literatures of Tibetan medicine,
      Bangjian were often classified into white, blue and black or white, blue and
      variegated according to color of flowers, leading to disordered varieties. In
      this paper, different Bangjian including their original plants and the main
      application varieties were studied and authenticated by textual research, wild
      specimen collection, investigation and collection of samples from Tibetan
      hospitals,Tibetan pharmaceutical factories and medical material markets. Results
      showed that Bangjian-including blue, black and variegated flowers were originated
      from 14 species and 3 varietas according to literatures, and the main application
      varieties mainly come from Ser. Ornatae of Sect. Monopodiae, such as Gentiana
      veitchiorum for the most, G. sino-ornata as well as G. lawrencei var. farreri.
      Suggestion about establishing the quality standard of Bangjian was gived, which
      provided reference in reasonable use and scientific research for Bangjian, and
      also had practical value for its clinical use and development.

PMID- 30200749
TI  - [Status analysis and strategic thinking on Mongolian medicine standardization].
AB  - Standardization is the progress of human civilization. It is also an important
      technical system for normalizing economy and social development and a basic
      element in the core competitive power of a country. This paper emphasized on the
      importance of accelerating the standardization of Mongolian medicine for
      international development of national medicine and improving the international
      competitiveness. Summed up the Mongolian medicine standardization work achieved
      the stage results. Achievements on Mongolian medicine standardization were
      summarized and the existed problems were also analyzed. Such as, imperfect
      Mongolian medicine standard system and operation mechanism, the lack of
      application and personnel of Mongolian medicine. Corresponding measures, such as
      improving the Mongolian medicine standardization system and its support system
      construction; establishing personnel long-term training mechanism; the
      establishment of Mongolian medicine standard implementation-promotion-evaluation
      feedback mechanism and other corresponding measures, were also provide.

PMID- 30200750
TI  - Does the old-fashioned sofosbuvir plus ribavirin treatment in genotype 2 chronic
      hepatitis C patients still works for Koreans?

PMID- 30200751
TI  - Surface Immobilization of Viruses and Nanoparticles Elucidates Early Events in
      Clathrin-Mediated Endocytosis.
AB  - Clathrin-mediated endocytosis (CME) is an important entry pathway for viruses.
      Here, we applied click chemistry to covalently immobilize reovirus on surfaces to
      study CME during early host-pathogen interactions. To uncouple chemical and
      physical properties of viruses and determine their impact on CME initiation, we
      used the same strategy to covalently immobilize nanoparticles of different sizes.
      Using fluorescence live microscopy and electron microscopy, we confirmed that
      clathrin recruitment depends on particle size and discovered that the maturation
      into clathrin-coated vesicles (CCVs) is independent from cargo internalization.
      Surprisingly, we found that the final size of CCVs appears to be imprinted on the
      clathrin coat at early stages of cargo-cell interactions. Our approach has
      allowed us to unravel novel aspects of early interactions between viruses and the
      clathrin machinery that influence late stages of CME and CCVs formation. This
      method can be easily and broadly applied to the field of nanotechnology,
      endocytosis, and virology.

PMID- 30200752
TI  - Spherical Ruthenium Disulfide-Sulfur-Doped Graphene Composite as an Efficient
      Hydrogen Evolution Electrocatalyst.
AB  - The exploition of cost-efficient and high-performance catalysts to boost hydrogen
      generation in overall water splitting is crucial to economically obtain green
      hydrogen energy. Herein, we propose a novel electrocatalyst consisting of
      spherical RuS2 on S-doped reduced graphene oxide (s-RuS2/S-rGO) with high
      catalytic behavior toward hydrogen evolution reaction (HER) in all pH conditions,
      especially in alkaline electrolytes. RuS2/S-rGO delivers small overpotentials of
      25 and 56 mV at current densities of 10 and 50 mA cm-2, respectively, and a low
      Tafel slope of 29 mV dec-1 with good stability for 100 h in basic solutions. This
      performance is comparable to and even exceeds that of documented representative
      electrocatalysts, including the benchmark Pt/C; since the price of Ru is about
      1/25th that of Pt, this novel electrocatalyst offers a low-cost alternative to Pt
      based HER electrocatalysts. Ruthenium-centered sites of RuS2 in this hybrid
      catalyst are responsible for the HER active sites, and S doping in RuS2 also
      exerts an important function for the HER activity; density functional theory
      calculations disclose that the water dissociation ability and adsorption free
      energy of hydrogen intermediate adsorption (Delta GH*) for RuS2 are very close to
      those of Pt. A homemade electrolyzer with an s-RuS2/S-rGO (cathode)//RuO2/C
      (anode) couple presents a relatively low voltage of 1.54 V at a current density
      of 20 mA cm-2, while maintaining negligible deactivation over a 24 h operation.

PMID- 30200755
TI  - Reactive Transport of Protons in Electro-Osmotic Displacements with Electrolyte
      Concentration Difference in a Microcapillary.
AB  - In this work, we model electro-osmotic displacement with electrolyte
      concentration difference in a microcapillary by incorporating proton transport
      coupled with surface complexation reaction and carbonate equilibrium. The
      hysteretic effect observed in experiments is well-captured by the model. By
      deriving the semianalytical solution of the nonlinear transport equation using
      method of characteristics, we elucidate the transport mechanism of protons by
      classifying their nonlinear transport behavior (shock/rarefaction/discontinuity)
      into several regimes depending on the concentration ratio and the pH. The model
      can be used to predict pH variation and characterizes surface property in electro
      osmotic experiments.

PMID- 30200753
TI  - Personal Exposure to PM2.5 Black Carbon and Aerosol Oxidative Potential using an
      Automated Microenvironmental Aerosol Sampler (AMAS).
AB  - Traditional methods for measuring personal exposure to fine particulate matter
      (PM2.5) are cumbersome and lack spatiotemporal resolution; methods that are time
      resolved are limited to a single species/component of PM. To address these
      limitations, we developed an automated microenvironmental aerosol sampler (AMAS),
      capable of resolving personal exposure by microenvironment. The AMAS is a
      wearable device that uses a GPS sensor algorithm in conjunction with a custom
      valve manifold to sample PM2.5 onto distinct filter channels to evaluate home,
      school, and other (e.g., outdoors, in transit, etc.) exposures. Pilot testing was
      conducted in Fresno, CA where 25 high-school participants ( n = 37 sampling
      events) wore an AMAS for 48-h periods in November 2016. Data from 20 (54%) of the
      48-h samples collected by participants were deemed valid and the filters were
      analyzed for PM2.5 black carbon (BC) using light transmissometry and aerosol
      oxidative potential (OP) using the dithiothreitol (DTT) assay. The amount of
      inhaled PM2.5 was calculated for each microenvironment to evaluate the health
      risks associated with exposure. On average, the estimated amount of inhaled PM2.5
      BC (MUg day-1) and OP [(MUM min-1) day-1] was greatest at home, owing to the
      proportion of time spent within that microenvironment. Validation of the AMAS
      demonstrated good relative precision (8.7% among collocated instruments) and a
      mean absolute error of 22% for BC and 33% for OP when compared to a traditional
      personal sampling instrument. This work demonstrates the feasibility of new
      technology designed to quantify personal exposure to PM2.5 species within
      distinct microenvironments.

PMID- 30200754
TI  - Bypassing Glutamic Acid Decarboxylase 1 (Gad1) Induced Craniofacial Defects with
      a Photoactivatable Translation Blocker Morpholino.
AB  - gamma-Amino butyric acid (GABA) mediated signaling is critical in the central and
      enteric nervous systems, pancreas, lungs, and other tissues. It is associated
      with many neurological disorders and craniofacial development. Glutamic acid
      decarboxylase (GAD) synthesizes GABA from glutamate, and knockdown of the gad1
      gene results in craniofacial defects that are lethal in zebrafish. To bypass this
      and enable observation of the neurological defects resulting from knocking down
      gad1 expression, a photoactivatable morpholino oligonucleotide (MO) against gad1
      was prepared by cyclization with a photocleavable linker rendering the MO
      inactive. The cyclized MO was stable in the dark and toward degradative enzymes
      and was completely linearized upon brief exposure to 405 nm light. In the course
      of investigating the function of the ccMOs in zebrafish, we discovered that
      zebrafish possess paralogous gad1 genes, gad1a and gad1b. A gad1b MO injected at
      the 1-4 cell stage caused severe morphological defects in head development, which
      could be bypassed, enabling the fish to develop normally, if the fish were
      injected with a photoactivatable, cyclized gad1b MO and grown in the dark. At 1
      day post fertilization (dpf), light activation of the gad1b MO followed by
      observation at 3 and 7 dpf led to increased and abnormal electrophysiological
      brain activity compared to wild type animals. The photocleavable linker can be
      used to cyclize and inactivate any MO, and represents a general strategy to parse
      the function of developmentally important genes in a spatiotemporal manner.

PMID- 30200756
TI  - Synthesis of Selective Estrogen Receptor Degrader GDC-0810 via Stereocontrolled
      Assembly of a Tetrasubstituted All-Carbon Olefin.
AB  - We report an efficient synthesis of GDC-0810 on the basis of a sequence involving
      a highly stereoselective lithium tert-butoxide-mediated enolization-tosylation
      (>=95:5 E: Z) and a Pd-catalyzed Suzuki-Miyaura cross-coupling as key steps.
      Global deprotection, pyrrolidine salt formation, and final active pharmaceutical
      ingredient (API) form control/isolation produced GDC-0810 free acid in a 40%
      overall yield with >99.0% purity as ascertained by HPLC analysis.

PMID- 30200757
TI  - Linear and Nonlinear Infrared Spectroscopies Reveal Detailed Solute-Solvent
      Dynamic Interactions of a Nitrosyl Ruthenium Complex in Solution.
AB  - In this work, the solvation of a nitrosyl ruthenium complex,
      [(CH3)4N][RuCl3(qn)(NO)] (with qn = deprotonated 8-hydroxyquinoline), which is a
      potential NO-releasing molecule in the bio-environment, was studied in two bio
      friendly solvents, namely deuterated dimethyl sulfoxide (dDMSO) and water (D2O).
      A blue-shifted NO stretching frequency was observed in water with respect to that
      in dDMSO, which was believed to be due to ligand-solvent hydrogen-bonding
      interactions, one N?O...D and particularly three Ru-Cl...D, that show competing
      effects on the NO bond length. The dynamic differences of the NO stretch in these
      two solvents were further revealed by transient pump-probe IR and two-dimensional
      IR results: faster vibrational relaxation and faster spectral diffusion (SD) were
      observed in D2O, confirming stronger solvent-solute interaction and also faster
      solvent structural dynamics in D2O than in DMSO. Further, a significant non
      decaying residual in the SD dynamics was observed in D2O but not in DMSO,
      suggesting the formation of a stable solvation shell in water due to strong multi
      site ligand-solvent hydrogen-bonding interactions, which is in agreement with the
      observed blue-shifted NO stretching frequency. This work demonstrates that small
      solvent molecules such as water can form a relatively rigid solvation shell for
      certain transition metal complexes due to cooperative ligand-solvent interactions
      and show slower dynamics.

PMID- 30200758
TI  - Kinetic Study of the Pyrolysis and Oxidation of Guaiacol.
AB  - Guaiacol or 2-methoxy phenol is one of the main primary tars produced during
      lignin pyrolysis. Tar conversion in the gas phase influences the production of
      gaseous and condensable products, and is also responsible for PAH and soot
      formation during biomass and bio-oil gasification or combustion. Guaiacol
      pyrolysis and oxidation under stoichiometric conditions were studied in a jet
      stirred reactor between 623 and 923 K for a residence time of 2 s and under a
      pressure of 800 Torr (106.7 kPa). Speciation was obtained thanks to online gas
      chromatography using flame ionization detection and mass spectrometry and allowed
      the quantification of 22 species in pyrolysis and 42 species in oxidation.
      Decomposition of guaiacol starts at 650 K, and a conversion degree of 50% is
      obtained at about 785 K in pyrolysis and 765 K in oxidation. The main products of
      reaction are pyrocatechol o-HOC6H4OH, o-hydroxybenzaldehyde, methylcatechols, and
      light products, such as methane, carbon monoxide, ethylene, and hydrogen. A
      detailed kinetic model based on a combustion model for light aromatics and
      anisole has been extended to guaiacol. Thermochemical data of guaiacol and main
      products were calculated theoretically at the CBS-QB3 level of theory. The model
      predicts well the conversion of guaiacol and the formation of the main products.
      Guaiacol decomposes mainly through a unimolecular O-C bond breaking to hydroxy
      phenoxy and methyl radicals in both pyrolysis and oxidation, but H atom
      abstractions are also of importance in the low temperature range of the study.
      The unimolecular mechanism leads mainly to pyrocatechol and methylcatechols,
      whereas the chain radical mechanism is responsible for the formation of
      hydroxybenzaldehyde. As for anisole but in a much lower extent, an early
      formation of benzene and soot precursors is observed.

PMID- 30200759
TI  - Formation, Alkylation, and Hydrolysis of Chiral Nonracemic N-Amino Cyclic
      Carbamate Hydrazones: An Approach to the Enantioselective alpha-Alkylation of
      Ketones.
AB  - The alpha-alkylation of ketones is a fundamental synthetic transformation. The
      development of asymmetric variants of this reaction is important given that
      numerous natural products, drugs, and related compounds exist as alpha
      functionalized ketones or derivatives thereof. We previously reported our
      preliminary studies on the development of a new enantioselective ketone alpha
      alkylation procedure using N-amino cyclic carbamate (ACC) auxiliaries. In
      comparison to other auxiliary-based methods, ACC alkylation offers a number of
      advantages and is both highly enantioselective and high yielding. Herein, we
      provide a full account of our studies on the enantioselective ACC ketone alpha
      alkylation method.

PMID- 30200760
TI  - Implications of Pyran Cyclization and Pterin Conformation on Oxidized Forms of
      the Molybdenum Cofactor.
AB  - The large family of mononuclear molybdenum and tungsten enzymes all possess the
      special ligand molybdopterin (MPT), which consists of a metal-binding dithiolene
      chelate covalently bound to a pyranopterin group. MPT pyran cyclization/scission
      processes have been proposed to modulate the reactivity of the metal center
      during catalysis. We have designed several small-molecule models for the Mo-MPT
      cofactor that allow detailed investigation into how pyran cyclization modulates
      electronic communication between the dithiolene and pterin moieties and how this
      cyclization alters the electronic environment of the molybdenum catalytic site.
      Using a combination of cyclic voltammetry, vibrational spectroscopy (FT-IR and
      rR), electronic absorption spectroscopy, and X-ray absorption spectroscopy,
      distinct changes in the Mo=O stretching frequency, Mo(V/IV) reduction potential,
      and electronic structure across the pterin-dithiolene ligand are observed as a
      function of pyran ring closure. The results are significant, for they reveal that
      a dihydropyranopterin is electronically coupled into the Mo-dithiolene group due
      to a coplanar conformation of the pterin and dithiolene units, providing a
      mechanism for the electron-deficient pterin to modulate the Mo environment. A
      spectroscopic signature identified for the dihydropyranopterin-dithiolene ligand
      on Mo is a strong dithiolene -> pterin charge transfer transition. In the absence
      of a pyran group bridge between pterin and dithiolene, the pterin rotates out of
      plane, largely decoupling the system. The results support a hypothesis that pyran
      cyclization/scission processes in MPT may function as a molecular switch to
      electronically couple and decouple the pterin and dithiolene to adjust the redox
      properties in certain pyranopterin molybdenum enzymes.

PMID- 30200761
TI  - DOTA Functionalized Cross-Linked Small-Molecule Micelles for Theranostics
      Combining Magnetic Resonance Imaging and Chemotherapy.
AB  - Herein, a new theranostic nanoplatform was built by introducing DOTA on the
      surface of the cross-linked small molecular micelles. This nanoplatform consisted
      of three parts: (1) Hydrophobic alkyl chain functioned with alkenes as cross
      linkable part to ensure the robust stability in vivo; (2) Hydrophilic DOTA for
      not only gadolinium ions complexion as MR imaging contrast agents but also
      platinum ions complexion as drug carriers; (3) Cisplatin as antitumor drug and MR
      imaging amplifier simultaneously. The metal loading content of the resulting
      Pt/Gd@DOTA-CSMs was up to 12 and 14 wt % for Gd(III) and Pt(II), respectively.
      The longitudinal relaxation rate of Gd@DOTA-CSMs (8.46 mM-1 s-1) was 2.6 times
      than that of the clinical Gd-DTPA (3.23 mM-1 s-1). When cisplatin was involved,
      not only great antitumor efficiency was achieved, but higher longitudinal
      relaxation rate of Pt/Gd@DOTA-CSMs (11.17 mM-1 s-1) was carried out due to the
      extension of rotational correlation time. The experiments of Balb/c mice bearing
      4T1 xenograft indicated that Pt/Gd@DOTA-CSMs had better antitumor activity, lower
      side effect than clinically used cisplatin, and greater MR imaging than Gd-DTPA.
      All the results proved that the nanoplatform of DOTA-CSMs held remarkable
      potential in the field of therapeutics.

PMID- 30200762
TI  - Modulating PCAF/GCN5 Immune Cell Function through a PROTAC Approach.
AB  - P300/CBP-associated factor (PCAF) and general control nonderepressible 5 (GCN5)
      are closely related epigenetic proteins, each containing an acetyltransferase
      domain and a bromodomain. Consistent with reported roles for these proteins in
      immune function, we find that PCAF-deficient macrophages exhibit a markedly
      reduced ability to produce cytokines upon stimulation with lipopolysaccharide
      (LPS). Investigating the potential to target this pathway pharmacologically, we
      show that chemical inhibition of the PCAF/GCN5 bromodomains is insufficient to
      recapitulate the diminished inflammatory response of PCAF-deficient immune cells.
      However, by generating the first PCAF/GCN5 proteolysis targeting chimera
      (PROTAC), we identify small molecules able to degrade PCAF/GCN5 and to potently
      modulate the expression of multiple inflammatory mediators in LPS-stimulated
      macrophages and dendritic cells. Our data illustrate the power of the PROTAC
      approach in the context of multidomain proteins, revealing a novel anti
      inflammatory therapeutic opportunity for targeting PCAF/GCN5.

PMID- 30200763
TI  - Effects of Hydrogen Bonding on Diffusion of Aromatic Compounds in Acetone: An
      Experimental Investigation from 268.2 to 328.2 K.
AB  - Diffusion coefficients of pseudoplanar aromatic compounds at infinite dilution in
      acetone have been measured at different temperatures by the Taylor dispersion
      technique. The data of the polar solutes that can form hydrogen bonds with
      acetone are compared with those of the nonpolar ones incapable of hydrogen
      bonding to quantify the effects of hydrogen-bonded association on diffusion. The
      effects are further found to correlate strongly with the overall hydrogen-bonded
      acidity of the polar solutes containing proton-donating groups. For the nonpolar
      solutes in this study, the diffusivities at different temperatures can be
      expressed very well by the recently developed molecular-modified fractional
      Stokes-Einstein relation with only two constants. An innovative model for solute
      diffusion in liquid solutions, which is constructed by combining the molecular
      hydrodynamic relation for nonpolar solutes with the overall hydrogen-bonded
      acidity scale for polar solutes, is introduced for representing the diffusivities
      of different types of disc-shaped molecules at various temperatures. An equation
      developed from this model is demonstrated to be capable of calculating a total of
      191 diffusion data of both the hydrogen-bonded and the nonassociated aromatic
      solutes in acetone from 268.2 to 328.2 K to a standard deviation of 2.7%.

PMID- 30200764
TI  - One-Pot Synthesis of High-Flux b-Oriented MFI Zeolite Membranes for Xe Recovery.
AB  - We demonstrate that b-oriented MFI (Mobil Five) zeolite membranes can be
      manufactured by in situ crystallization using an intermediate amorphous SiO2
      layer. The improved in-plane growth by using a zeolite growth modifier leads to
      fusion of independent crystals and eliminates boundary gaps, giving good
      selectivity in the separation of CO2/Xe mixtures. The fast diffusion of CO2
      dominates the overall membrane selectivity toward the CO2/Xe mixture. Because of
      the straight and short [010] channels, the obtained CO2 permeation fluxes are
      several orders of magnitude higher than those of carbon molecular sieving
      membranes and polymeric membranes, opening opportunities for Xe recovery from
      waste anesthetic gas.

PMID- 30200765
TI  - Where and How Does an Organic Molecule Having a C-X Bond Release X- Anion Like an
      Inorganic Compound? A Theoretical Study.
AB  - In this research, at first, a comparative DFT study on hydride or fluoride
      release from a number of known orthoamides, their fluorine derivative having a
      central C-F bond and some simple organic compounds, is reported. The obtained
      data show that orthoamides release hydride or fluoride anions much easier than do
      other known organic compounds studied here. Interestingly, three simulated
      orthoamides having a central C-F bond, spontaneously and like an inorganic
      compound, release fluoride anion upon dissolving in polar solvents. The
      calculations confirmed that hyperconjugation interactions in the initial
      orthoamides facilitate the anion release from these compounds. However, the data
      clearly show that the proper overlap of an empty p orbital of the central carbon
      atom with adjacent lone-pair orbitals of nitrogen atoms ( lpN -> lp*C or, in
      other words, the ppi-ppi interaction) in the resulting carbocations is a more
      important factor that must be taken into consideration when designing the
      hydride, fluoride, or other anion releasing agents. In addition, for the first
      time, a mechanism of hydride and fluoride removal from the orthoamides either
      through their reaction with BH3 and BF3 molecules, respectively, or upon their
      protonation is provided. To continue and for generalization of results to other
      groups attached to the central carbon atom of orthoamides, the reactions of H+
      with orthoamides having the CH3, OH, CN, NH2, or C5H5 substituents were studied.
      The results showed that in all cases and in both gas and solution phases the
      above substituents easily leave the carbon atom as an anion and bond to H+. Thus,
      we have to conclude that upon the reaction of orthoamides with usual Lewis acids,
      many types of substituents on their central carbon atom can leave these compounds
      as anions.

PMID- 30200766
TI  - Nonadiabatic Excited-State Dynamics with Machine Learning.
AB  - We show that machine learning (ML) can be used to accurately reproduce
      nonadiabatic excited-state dynamics with decoherence-corrected fewest switches
      surface hopping in a 1-D model system. We propose to use ML to significantly
      reduce the simulation time of realistic, high-dimensional systems with good
      reproduction of observables obtained from reference simulations. Our approach is
      based on creating approximate ML potentials for each adiabatic state using a
      small number of training points. We investigate the feasibility of this approach
      by using adiabatic spin-boson Hamiltonian models of various dimensions as
      reference methods.

PMID- 30200767
TI  - Acaricidal Activity of Cyclodipeptides from Bacillus amyloliquefaciens W1 against
      Tetranychus urticae.
AB  - Bioassay-guided fractionation of the supernatant of the biocontrol strain
      Bacillus amyloliquefaciens W1 led to the isolation of eight acaricidal
      cyclodipeptides from the active fractions by column chromatography separation and
      HPLC purification. The chemical structures of these compounds were identified as
      cyclo-(Gly-l-Phe), 2, cyclo-(l-Phe- trans-4-OH-l-Pro), 3, cyclo-(Gly-l-Tyr), 4,
      cyclo-(l-Ala-l-Pro), 5, cyclo-(l-Pro- trans-4-OH-l-Pro), 6, cyclo-(Gly-l-Pro), 7,
      cyclo-(l-Pro-l-Pro), 8, and cyclo-(l-Tyr- trans-4-OH-l-Pro), 9. Those
      cyclodipeptides displayed significant acaricidal activities with LC50 values of
      13.85-98.24 MUM. Cyclo-(l-Tyr- trans-4-OH-l-Pro) (LC50 13.85 MUM) was five times
      more effective than the positive control abamectin (LC50 72.06 MUM). The results
      indicated that the hydroxyl group is an important component. This is the first
      report on the acaricidal capabilities of cyclodipeptides against Tetranychus
      urticae. The results revealed that the acaricidal activity of the biocontrol
      strain B. amyloliquefaciens W1 was dependent on its constituent cyclodipeptides,
      which have the potential to be safe and environmentally friendly acaricides.

PMID- 30200768
TI  - Quantitative Proteomic Profiling Reveals Key Pathways in the Anticancer Action of
      Methoxychalcone Derivatives in Triple Negative Breast Cancer.
AB  - Triple negative breast cancer is an aggressive, heterogeneous disease with high
      recurrence and metastasis rates even with modern chemotherapy regimens and thus
      is in need of new therapeutics. Here, three novel synthetic analogues of
      chalcones, plant-based molecules that have demonstrated potency against a wide
      variety of cancers, were investigated as potential therapeutics for triple
      negative breast cancer. These compounds exhibit IC50 values of ~5 MUM in triple
      negative breast cancer cell lines and are more potent against triple negative
      breast cancer cell lines than against nontumor breast cell lines according to
      viability experiments. Tandem mass tag-based quantitative proteomics followed by
      gene set enrichment analysis and validation experiments using flow cytometry,
      apoptosis, and Western blot assays revealed three different anticancer mechanisms
      for these compounds. First, the chalcone analogues induce the unfolded protein
      response followed by apoptosis. Second, increases in the abundances of MHC-I
      pathway proteins occurs, which would likely result in immune stimulation in an
      organism. And third, treatment with the chalcone analogues causes disruption of
      the cell cycle by interfering with microtubule structure and by inducing G1 phase
      arrest. These data demonstrate the potential of these novel chalcone derivatives
      as treatments for triple negative breast cancer, though further work evaluating
      their efficacy in vivo is needed.

PMID- 30200770
TI  - Risk Factors for Lower Limb Deep Vein Thrombosis in Patients With Single-Level
      Lumbar Fusion: A Prospective Study of 710 Cases.
AB  - Lower limb deep vein thrombosis (DVT) is not an uncommon postoperative
      complication of spinal fusion surgery. However, the related risk factors
      identified in previous studies remain controversial. This study aimed to
      investigate risk factors for lower limb DVT in patients with single-level lumbar
      fusion surgery. Between January 2010 and December 2016, a total of 710 patients
      undergoing lumbar fusion were recruited for this study, including 172 males and
      538 females (aged 18-75 years). Deep vein thrombosis was detected by
      ultrasonography. Accordingly, patients were divided into the DVT group and the
      non-DVT group and compared in terms of operative data, underlying diseases, and
      biochemical data. Additionally, logistic regression analysis was performed to
      identify risk factors for lower limb DVT. The incidence of lower limb DVT was
      11.8% (84 of 710 cases). Five patients were symptomatic, with lower limb pain and
      swelling. Two patients developed pulmonary embolism and 1 died. Binary logistic
      regression indicated that advanced age ( P = .001, odds ratio [OR] = 2.86, 95%
      CI: 1.85-5.12), hypertension ( P = .006, OR = 4.10, 95% CI: 1.09-2.30), and
      increased d-dimer ( P < .001, OR = 3.49, 95% CI: 2.05-6.36) were risk factors for
      postoperative DVT. In conclusion, for patients with single-level lumbar fusion,
      advanced age, increased d-dimer, and hypertension may contribute to DVT
      development after spinal fusion surgery. Therefore, patients with these risk
      factors should be protected during the perioperative period.

PMID- 30200769
TI  - Selective-Area Superconductor Epitaxy to Ballistic Semiconductor Nanowires.
AB  - Semiconductor nanowires such as InAs and InSb are promising materials for
      studying Majorana zero modes and demonstrating non-Abelian particle exchange
      relevant for topological quantum computing. While evidence for Majorana bound
      states in nanowires has been shown, the majority of these experiments are marked
      by significant disorder. In particular, the interfacial inhomogeneity between the
      superconductor and nanowire is strongly believed to be the main culprit for
      disorder and the resulting "soft superconducting gap" ubiquitous in tunneling
      studies of hybrid semiconductor-superconductor systems. Additionally, a lack of
      ballistic transport in nanowire systems can create bound states that mimic
      Majorana signatures. We resolve these problems through the development of
      selective-area epitaxy of Al to InSb nanowires, a technique applicable to other
      nanowires and superconductors. Epitaxial InSb-Al devices generically possess a
      hard superconducting gap and demonstrate ballistic 1D superconductivity and near
      perfect transmission of supercurrents in the single mode regime, requisites for
      engineering and controlling 1D topological superconductivity. Additionally, we
      demonstrate that epitaxial InSb-Al superconducting island devices, the building
      blocks for Majorana-based quantum computing applications, prepared using
      selective-area epitaxy can achieve micron-scale ballistic 1D transport. Our
      results pave the way for the development of networks of ballistic superconducting
      electronics for quantum device applications.

PMID- 30200772
TI  - The effect of abdominal contrast-enhanced CT on DNA double-strand breaks in
      peripheral blood lymphocytes: an in vitro and in vivo study.
AB  - Background As abdominal computed tomography (CT) radiation dose can be higher
      compared with other organ systems, monitoring the radiation exposure from this
      exam type is especially important. Purpose To evaluate the effect of abdominal
      contrast-enhanced CT (CE-CT) on levels of DNA double-strand breaks (DSBs) in
      peripheral blood lymphocytes. Material and Methods This study was performed in
      two parts: (i) an in vitro study: venous blood samples from 12 volunteers were
      divided into four groups. Samples in group A did not undergo radiation exposure,
      while groups B, C, and D received one CT scan with 1-3 times the radiation dose
      equivalent to abdominal CE-CT scan, respectively; and (ii) an in vivo study:
      blood was taken before CT and 5 min after CT in 30 patients. Lymphocytes were
      isolated and stained by immunofluorescence of gamma-H2AX protein. DSB levels were
      compared by variance analysis or paired t-test. The relationship between
      radiation dose and gamma-H2AX focus increase was analyzed using Pearson
      correlation analysis. Results In the in vitro study, DSBs levels in groups B, C,
      and D were 49.4%, 96.6%, and 149.4% higher than those in Group A, respectively
      (all P < 0.001). Radiation dose in the four subgroups had a linear correlation to
      DSB levels ( P < 0.001). In the in vivo study, the DSB level was 43.5% higher
      after CT ( P < 0.001). Conclusion Abdominal CE-CT significantly increased DSB
      levels in both in vitro and in vivo experiments. A positive linear correlation of
      CT radiation dose with intracellular DSBs levels was observed in the in vitro
      study.

PMID- 30200774
TI  - Effectiveness of a Trauma-Informed Care Initiative in a State Child Welfare
      System: A Randomized Study.
AB  - Trauma-informed care (TIC) initiatives in state child welfare agencies are
      receiving more attention, but little empirical evidence exists as to their
      efficacy. The purpose of this study was to assess changes in self-reported
      practices and perceptions of child welfare staff involved in a multifaceted,
      statewide TIC intervention. Ten child welfare offices were matched and randomized
      to an early or delayed cohort. Staff were surveyed at Time 1 prior to any
      intervention, Time 2 postintervention for Cohort 1, and Time 3 postintervention
      for Cohort 2. The survey covered six domains: trauma screening, case planning,
      mental health and family involvement, progress monitoring, collaboration, and
      perceptions of the state's overall system performance. Linear mixed modeling
      assessed the effect of the intervention. Cohort by time interaction was
      significant for three intervention targets. We demonstrate, using a rigorous
      study design, the mixed results of a multimodal intervention to improve trauma
      informed attitudes, practices, and system performance. TIC initiatives must
      account for complex, dynamic contextual factors.

PMID- 30200775
TI  - Editorial Comment on: Surgical Approach Does Not Impact Margin Status After
      Partial Nephrectomy for Large Renal Masses by Ayangbesan et al.

PMID- 30200776
TI  - Personality, Self-Esteem, and Perceived Stress in Communal Residences Supporting
      Recovery.
AB  - The current study examined the relationships between a personality metatrait
      (Stability consisting of conscientiousness, agreeableness, and neuroticism), self
      esteem, and stress in an adult population of individuals with substance use
      disorders living in recovery homes. Adults ( N = 229) residing in 42 residential
      recovery settings were interviewed as part of the first wave of a longitudinal
      study in three sites. Standard error of the mean analysis found significant
      effects for several demographic variables on Stability, and Stability was
      significantly related both directly and indirectly to stress. These findings
      suggest that individual differences at entry may influence recovery home effects
      and may be important to developing more effective aftercare systems.

PMID- 30200777
TI  - Off-Label Use of Antipsychotic Agents in Dementia: Evidence for the Revision of
      the Reimbursement Policy.
AB  - BACKGROUND: Harmonized requirements apply for the marketing authorization of
      medicinal products in the EU Member States. On the contrary, the national
      legislations on the drug reimbursement are not harmonized. The aim of this study
      was to find out if they are robust enough to ensure high standards of public
      health protection with focus on the symptomatic treatment of dementia in the
      elderly. METHODS: A computerized search of authorized therapeutic indications of
      haloperidol and trihexyphenidyl in the national databases of 8 EU member states
      and an analysis of the national legislation on reimbursement policies in
      Lithuania and Latvia was performed. RESULTS: There is a discrepancy in the
      decisions on the marketing authorization vs the reimbursement in Lithuania and
      Latvia (reimbursement of haloperidol and trihexyphenidyl for the off-label
      treatment of dementia). CONCLUSIONS: National legislation on the drug
      reimbursement in Lithuania and Latvia does not provide safeguards for public
      health at the same level as the marketing authorization does. Absence of a
      revision of former decisions in the light of new evidence is a critical weakness
      of the drug reimbursement in Lithuania and Latvia. Reimbursement for the off
      label indications may pose a risk to public health.

PMID- 30200778
TI  - Engineering of Human Mesenchymal Stem/Stromal Cells with Vascular Endothelial
      Growth Factor-Encoding Minicircles for Angiogenic Ex Vivo Gene Therapy.
AB  - Peripheral artery disease (PAD) is a debilitating and prevalent condition
      characterized by blockage of the arteries, leading to limb amputation in more
      severe cases. Mesenchymal stem/stromal cells (MSC) are known to have intrinsic
      regenerative properties that can be potentiated by the introduction of pro
      angiogenic genes such as the vascular endothelial growth factor (VEGF). Herein,
      the use of human bone marrow MSC transiently transfected with minicircles
      encoding for VEGF is proposed as an ex vivo gene therapy strategy to enhance
      angiogenesis in PAD patients. The VEGF gene was cloned in minicircle and
      conventional plasmid vectors and used to transfect bone marrow-derived MSC ex
      vivo. VEGF expression was evaluated both by quantitative polymerase chain
      reaction and enzyme-linked immunosorbent assay. The number of VEGF transcripts
      following MSC transfection with minicircles increased 130-fold relative to the
      expression in non-transfected MSC, whereas for the plasmid (pVAX1)-based
      transfection, the increase was 50-fold. Compared to the VEGF basal levels
      secreted by MSC (11.1 +/- 3.4 pg/1,000 cells/day), significantly higher values
      were detected by enzyme-linked immunosorbent assay after both minicircle and
      pVAX1 transfection (644.8 +/- 82.5 and 508.3 +/- 164.0 pg/1,000 cells/day,
      respectively). The VEGF overexpression improved the angiogenic potential of MSC
      in vitro, as confirmed by endothelial cell tube formation and cell migration
      assays, without affecting the expansion potential ex vivo, as well as
      multilineage differentiation capacity or immunophenotype of MSC. Although
      preclinical in vivo studies are required, these results suggest that minicircle
      mediated VEGF gene delivery, combined with the unique properties of human MSC,
      could represent a promising ex vivo gene therapy approach for an improved
      angiogenesis in the context of PAD.

PMID- 30200780
TI  - Evaluation of genetic parameters of 23 autosomal STR loci in a Southern Chinese
      Han population.
AB  - AIM: To evaluate the 23 autosomal short tandem repeat (STR) loci included in
      GoldenEyeTM 25 A kit using forensic human identification and paternity testing.
      SUBJECTS AND METHODS: In total, 3751 unrelated individuals from the Southern
      Chinese Han population were genotyped with the 5-dye GoldenEyeTM 25 A multiplex
      amplification system. PCR products were separated using arrayed capillary
      electrophoresis. Allele frequencies and forensic parameters for the 23 autosomal
      STR loci were statistically analysed. RESULTS: A total of 344 alleles were
      observed, with corresponding allelic frequencies ranging from 0.0001-0.5519 for
      the 23 STR loci. No significant deviation from the Hardy-Weinberg equilibrium and
      linkage disequilibrium was observed. The combined power of discrimination (CPD)
      was 1-1.6290 * 10-28 and the combined power of exclusion (CPE) was 0.999 999 999
      89 and 0.999 999 286 93 for trio and duo cases, respectively. From 3865 meioses,
      87 mutation events were discovered. The mutation rate varied from 0-0.00285 for
      each locus. One-step mutation accounted for 94.25% of total mutations. The ratio
      of paternal vs maternal mutation was 3.76:1.13 kinds of n/(n + 1) heterozygote
      genotypes were observed. CONCLUSIONS: The results show that 23 STR loci of
      GoldenEyeTM 25 A kit are highly polymorphic in the Southern Chinese Han
      population, indicating the kit is suitable for forensic application.

PMID- 30200781
TI  - Efficacy and safety of tapentadol prolonged release formulation in the treatment
      of elderly patients with moderate-to-severe chronic osteoarthritis knee pain: a
      pooled analysis of two double-blind, randomized, placebo-, and active-controlled
      trials.
AB  - OBJECTIVE: To compare efficacy and safety of tapentadol prolonged release (PR) vs
      oxycodone controlled release (CR) in younger patients (<65 years of age) and in
      elderly patients (>=65 and >=75 years of age) in the treatment of moderate-to
      severe chronic osteoarthritis (OA) knee pain. METHODS: Data from two double
      blind, randomized, placebo-, and oxycodone CR-controlled phase 3 trials were
      pooled and stratified by age. Primary efficacy end-points were change from
      baseline in average pain intensity at week 12 (US end-point) and over the entire
      maintenance period (non-US end-point). RESULTS: A total of 1357 patients <65
      years, 653 patients >=65 years, and 176 patients >=75 years of age were assessed.
      The comparison between tapentadol PR and oxycodone CR showed numerically better
      pain relief under tapentadol PR for both primary end-points in all three age
      groups. More favorable improvements were also observed for patient global
      impression of change, the Short Form-36 physical component score, and EuroQoL
      5Dimensions health status index. In the elderly, incidences of dizziness and
      somnolence were comparable between active treatments, but incidences of nausea,
      vomiting, and constipation were considerably lower under tapentadol PR. Treatment
      completion rates were lowest under oxycodone CR; > 50% of elderly oxycodone CR
      patients named side-effects as the main reason for discontinuation. CONCLUSIONS:
      Tapentadol PR was effective in the treatment of moderate-to-severe chronic OA
      pain in elderly and younger patients. Compared to oxycodone CR, the overall and
      the gastrointestinal tolerability profile in particular were better in all
      tapentadol PR groups, regardless of age.

PMID- 30200779
TI  - An evaluation of tedizolid for the treatment of MRSA infections.
AB  - INTRODUCTION: Methicillin-resistant Staphylococcus aureus (MRSA)is a common
      pathogen in acute bacterial skin and soft tissue infections (ABSSSIs), nosocomial
      pneumonia, bacteremia, endocarditis, as well as diabetic foot, bone, and joint
      infections. Areas covered: This review summarizes the randomized controlled
      trials that evaluated the clinical efficacy of tedizolid in ABSSSIs, which is
      currently the only United States Food and Drug Administration-labeled indication
      for tedizolid. Expert opinion: Tedizolid has several potential advantages over
      linezolid including once-daily dosing, shorter duration of therapy, and increased
      tolerability. However, its cost will likely limit its adoption for ABSSSIs with
      MRSA because other oxazolidinone antibiotics are available in less costly generic
      versions. Tedizolid is also currently being investigated for its use in other
      MRSA infections including nosocomial pneumonia as well as diabetic foot, bone,
      and joint infections and tedizolid's use in these disease states appears more
      promising. Potential indications for future clinical investigation of tedizolid's
      efficacy and safety include bacteremia and meningitis.

PMID- 30200782
TI  - High AMY1 copy number protects against obesity in Portuguese young adults.
AB  - BACKGROUND: The highly polymorphic copy number variation (CNV) in the salivary
      amylase gene (AMY1) has been associated with obesity in different populations.
      However, some authors have failed to reproduce these findings. AIM: To
      investigate the association between AMY1 CNV and obesity in young adults of
      Portuguese origin. SUBJECTS AND METHODS: This study evaluated AMY1 gene copy
      number (CN) in 262 individuals: 155 females and 107 males, aged 18-34 years-old
      (mean age = 21.08). The number of AMY1 copies was estimated in a QX100 droplet
      digital PCR (ddPCR) system (Bio-Rad Laboratories, Hercules, CA). RESULTS:
      Defining a case group with obese and overweight individuals, logistic regression
      did not show a significant association between AMY1 CNV and risk of
      overweight/obesity in the whole population (p = 0.489). However, after testing
      case-control data in the sub-set of samples above the third quartile (CN >=10), a
      significant association was found between lower AMY1 copy number and risk of
      obesity (OR = 0.532; p = 0.034), even when adjusted for age and sex (OR = 0.527;
      p = 0.039). In concordance, all participants with >10 AMY1 copies were normal
      weight controls (n = 20) or overweight (n = 6). CONCLUSION: The results suggest
      that high AMY1 gene copy number protects against obesity in Portuguese young
      adults.

PMID- 30200784
TI  - Macular Thickness and Mesopic Visual Acuity in Healthy Older Subjects.
AB  - : Purpose/Aim: Impaired mesopic visual acuity (VA) is a risk factor for incident
      early age-related macular degeneration (AMD) This study examines relationships
      between macular thickness measurements and photopic or mesopic VA in healthy
      eyes. MATERIALS AND METHODS: In 38 young and 39 older healthy individuals, total,
      inner, and outer retinal layer (IRL and ORL) thicknesses were measured in the
      macula region through spectral-domain optical coherence tomography (SD-OCT).
      Measurements were made across three subfields centered at the fovea: central
      foveal, pericentral, and peripheral. Best-corrected distance high-contrast (HC)
      and low-contrast (LC) VA were measured using Bailey-Lovie logMAR letter charts
      under photopic and mesopic luminance conditions. In addition, the low luminance
      deficit in VA (LLD, difference between photopic and mesopic VA) was calculated.
      Relationships were examined through Spearman correlation in each age group and
      through multiple linear regressions across all eyes. RESULTS: No significant
      correlations were detected between photopic VA (HC-VA and LC-VA) and macular
      thickness measurements in each age group. In mesopic conditions, age and pupil
      size were independent predictors of HC-VA (p = 0.001) and age and pericentral ORL
      thickness predictors of LC-VA (p = 0.001). Central foveal thickness emerged as
      the unique independent predictor of LLD (HC-VA, p = 0.013 and LC-VA, p = 0.005).
      Only in the older age group, was central foveal thicknesses correlated with LLD
      (HC-VA, r = + 0.45; p = 0.004 and LC-VA, r = + 0.33, p = 0.038). CONCLUSIONS:
      Greater macular thicknesses were related to worse mesopic VA and low luminance
      deficit in healthy subjects.

PMID- 30200783
TI  - Gene Therapy for Hemoglobinopathies.
AB  - Gene therapy for beta-thalassemia and sickle-cell disease is based on
      transplantation of genetically corrected, autologous hematopoietic stem cells.
      Preclinical and clinical studies have shown the safety and efficacy of this
      therapeutic approach, currently based on lentiviral vectors to transfer a beta
      globin gene under the transcriptional control of regulatory elements of the beta
      globin locus. Nevertheless, a number of factors are still limiting its efficacy,
      such as limited stem-cell dose and quality, suboptimal gene transfer efficiency
      and gene expression levels, and toxicity of myeloablative regimens. In addition,
      the cost and complexity of the current vector and cell manufacturing clearly
      limits its application to patients living in less favored countries, where
      hemoglobinopathies may reach endemic proportions. Gene-editing technology may
      provide a therapeutic alternative overcoming some of these limitations, though
      proving its safety and efficacy will most likely require extensive clinical
      investigation.

PMID- 30200785
TI  - Three-Dimensional Printing for Craniofacial Surgery: A Single Institution's 5
      Year Experience.
AB  - BACKGROUND: As 3-dimensional (3D) printers and models become more widely
      available and increasingly affordable, surgeons may consider investing in a
      printer for their own cleft or craniofacial center. To inform surgeons
      considering adoption of this evolving technology, this study describes one multi
      surgeon center's 5-year experience using a 3D printer. METHODS: This study
      included 3D models printed between October 2012 and October 2017. A 3D Systems
      ZPrinter 650 was used to create all models. Models were subclassified by type
      (craniofacial vs noncraniofacial) and diagnosis, and the cost of consumable
      materials was recorded. A survey was distributed to craniofacial team members who
      used the printed models. Likert scales and free texts were used for responses
      about lessons learned and the usefulness of the printer for different
      craniofacial indications. RESULTS: A total of 106 models were printed at this
      institution during the 5-year time period. Printing times were 7.4 +/- 1.9 hours
      for complete skulls and 6.0 +/- 1.7 hours for maxillofacial prints. The average
      cost for a complete skull was about US$60 in material cost alone. The 3D printer
      was most frequently used for complex craniosynostosis, hemifacial microsomia
      syndrome, and fibrous dysplasia cases. The surgeons found the printer to be most
      useful for planning complex facial orthognathic cases and least useful for
      routine single-suture synostosis. CONCLUSION: Three-dimensional printing was
      found to be helpful for all 4 craniofacial surgeons, who would all invest again
      in a 3D printer. For lower volume centers, commercially printed models may be a
      more cost-effective alternative.

PMID- 30200786
TI  - Impact of acculturation on depression, perceived stress and self-esteem in young
      Middle Eastern American adults.
AB  - BACKGROUND: Human biologists have a longstanding interest in understanding the
      biological and health impacts of migration. Acculturation, the cultural
      adjustment that a group or individual experiences when previously separate
      cultures interact, has been found to be one pathway through which migration may
      impact human biology and health, not only for the migrants themselves, but also
      their descendants. AIM: The authors conducted a pilot study to examine the
      relationship between acculturation and perceived stress, self-esteem and
      depression among young Middle-Eastern American adults. SUBJECT AND METHODS:
      Survey data were collected from 48 young Middle-Eastern American adults.
      Participants were divided into one of two acculturation categories, integrated
      (American and Middle Eastern culture oriented) and assimilated (American culture
      oriented). Health measures were compared between these acculturation categories.
      RESULTS: Integrated individuals had significantly lower stress (F = 8.1, p <
      0.01) and depression (F = 10.8, p < 0.01) than assimilated individuals.
      Integrated individuals had lower self-esteem than assimilated individuals (F =
      5.0, p < 0.05). Generational status, a proxy used for acculturation, was only
      significantly associated with self-esteem (F = 3.15, p = 0.05). CONCLUSION: This
      pilot study furthers understanding of the effects acculturation can have on
      perceived stress and mental health among young Middle-Eastern Americans. Future
      research should incorporate biological measures of stress to determine the
      physiological impacts of acculturation.

PMID- 30200787
TI  - Combined effects of workplace bullying and perceived organizational support on
      employee behaviors: does resource availability help?
AB  - BACKGROUND AND OBJECTIVE: This research examines the detrimental effects of
      workplace bullying as a social stressor on employees' job performance,
      organizational retaliatory behaviors, and organizational citizenship behaviors
      and how the availability of support can reduce the negative impact of bullying.
      Using social exchange theory and the conservation of resources theory as
      theoretical frameworks, we propose that workplace bullying drains personal
      resources, leading to reduced job performance, low citizenship behaviors, and
      increased organizational retaliatory behaviors. We also propose that perceived
      organizational support acts as moderator, such that it reduces the detrimental
      effects of bullying on employee behaviors. RESEARCH DESIGN AND METHODS: We tested
      our hypotheses in two field studies (N = 478 and N = 395) conducted in Pakistan.
      RESULTS: The results of both studies supported the assertion that workplace
      bullying exacerbates employees' job performance, reduces organizational
      citizenship behaviors and intensifies organizational retaliatory behaviors. The
      idea that perceived organizational support would moderate the bullying-work
      behavior relationships found mixed support. While perceptions of organizational
      support reinforced the bullying-job performance and bullying-retaliatory
      behaviors relationships, it did not moderate the bullying-citizenship behaviors
      relationship in the suggested direction. CONCLUSION: The findings show that
      workplace bullying leads to more organizational citizenship behaviors when
      employee's perceptions of organizational support is high.

PMID- 30200788
TI  - The impact of the telerehabilitation group aphasia intervention and networking
      programme on communication, participation, and quality of life in people with
      aphasia.
AB  - PURPOSE: Aphasia group therapy can result in improvements in communication,
      participation and quality of life (QOL). However, evidence for aphasia group
      interventions with combined aims across the International Classification of
      Functioning, Disability and Health (ICF) is limited. TeleGAIN is a holistic
      aphasia group intervention that can be delivered via telepractice. This study
      builds on prior pilot work and addresses the need for additional research into
      the effectiveness of TeleGAIN. The aim of this study was to describe changes in
      aphasia severity, communication related QOL and participation, for people with
      chronic aphasia following TeleGAIN. METHOD: Nineteen participants with aphasia
      were assessed on a range of outcome measures before and after a twelve-week block
      of TeleGAIN delivered via web based videoconferencing. Treatment provided
      opportunities to participate in conversation, engage with others with aphasia and
      complete functional communication activities. RESULT: Statistical analyses
      revealed statistically significant improvements in communication related QOL,
      increased engagement in communicative activities, and decreased aphasia severity.
      CONCLUSION: Results from this study suggest that the online delivery of a multi
      purpose group intervention for people with aphasia can result in improved
      communication, communicative participation, and QOL. It also highlights the
      potential for intervention provided via telepractice to offer an alternative to
      face-to-face services.

PMID- 30200789
TI  - Choosing the appropriate salvage therapy for B-cell non-Hodgkin lymphoma.

PMID- 30200790
TI  - The impact of gestational sac size on the effectiveness and safety of high
      intensity focused ultrasound combined with ultrasound-guided suction curettage
      treatment for caesarean scar pregnancy.
AB  - OBJECTIVE: To evaluate the correlation between the gestational sac size and the
      effect and safety of high intensity focused ultrasound (HIFU) combined with
      ultrasound-guided suction curettage for caesarean scar pregnancy (CSP). METHODS:
      Seventy-six patients with CSP were enrolled. Based on their gestational sac size,
      patients were divided into three groups: Group 1 (n = 16, 10-20 mm), Group 2 (n =
      28, 21-30 mm) and Group 3 (n = 32, >30 mm). All of them were treated by HIFU
      combined with ultrasound-guided suction curettage. Baseline characteristics,
      parameters and adverse events of HIFU, and intraoperative hemorrhage during
      ultrasound-guided suction curettage were recorded. RESULTS: The median treatment
      time and average treatment intensity of HIFU in Group 3 were significantly higher
      than Group 1 (p < .05); the median HIFU treatment power in Group 2 and Group 3
      were both significantly higher than that of Group 1 (p < .05). The median
      sonication time of HIFU in Group 3 was significantly longer than patients in the
      other two groups (p < .05). The size of the gestational sac had a positive
      correlation with all the above-mentioned parameters of HIFU and blood loss during
      ultrasound-guided suction curettage (p < .05). No statistically significant
      differences were observed among the three groups in the duration of vaginal
      bleeding post-curettage and the time necessary for serum beta-hCG to return to
      normal levels (p > .05). CONCLUSIONS: HIFU combined with ultrasound-guided
      suction curettage is a safe and effective clinical approach for CSP. Gestational
      sac size is a meaningful factor for predicting the efficacy and safety of HIFU
      treatment and hemorrhage during ultrasound-guided suction curettage.

PMID- 30200791
TI  - Long-term outcomes and prognostic analysis of percutaneous radiofrequency
      ablation in liver metastasis from breast cancer.
AB  - OBJECTIVE: To evaluate the long-term efficacy and prognostic factors of
      ultrasound-guided percutaneous radiofrequency ablation (RFA) for breast cancer
      liver metastasis (BCLM). METHODS: Between 2000 and 2015, 69 patients who
      underwent ultrasound-guided percutaneous RFA for BCLM and had regular follow-up
      examinations were included. All patients had undergone resection of the primary
      breast cancer and had received chemotherapy, endocrine therapy or both after
      surgery. The sample included two males and 67 females with an average age of 50.3
      +/- 10.0 years (31-76 y). The mean maximum diameter of metastatic lesions in the
      liver was 2.9 +/- 1.4 cm (1.0-6 cm). Thirty-five patients had a single
      metastasis, while 34 patients had multiple liver metastases (2-5 lesions).
      Survival results were generated using Kaplan-Meier estimates and a multivariate
      analysis was performed using the Cox regression model. RESULTS: In total, 92 RFA
      sessions were performed and 135 BCLM lesions were treated. Major complications
      occurred in one of the 92 sessions (1.1%). Technical efficacy was achieved in
      92.6% of lesions (125/135 lesions). Local tumor progression occurred in 11.6%
      (8/69) of patients and new intrahepatic metastasis occurred in 55.1% (38/69) of
      patients. From the time of initial RFA, the median overall survival was 26
      months, and the one-, two-, three- and five -year survival rates were 81.8, 50.1,
      25.3 and 11.0%, respectively. Based on the multivariate analysis, the following
      three factors were identified as independent prognostic factors for overall
      survival: tumor size (p = .017), positive estrogen receptor status (p = .009) and
      extrahepatic metastatic disease (p = .001). The median progression-free survival
      was 24 months, and the one-, two-, three- and five -year survival rates after RFA
      were 77.4, 47.0, 23.7 and 8.5%, respectively. Additionally, the independent
      prognostic factors for progression-free survival included tumor size (p = .011),
      ER positivity (p = .001), margin size (p = .017) and extrahepatic metastatic
      disease (p < .001). CONCLUSION: The results of this study showed that RFA is a
      safe and locally effective method for the treatment of BCLM, especially in
      patients with lesions measuring less than 3 cm in diameter, a single liver
      metastasis, positive estrogen receptor status and no extrahepatic metastases.
      Also, patients with margin size >10 mm had no local tumor progression.

PMID- 30200792
TI  - Sex-age-specific handgrip strength and mortality in an incident hemodialysis
      cohort: The risk explained by nutrition and comorbidities.
AB  - OBJECTIVE:: To investigate associations of sex-age-specific handgrip strength by
      a dynamometer with all-cause mortality and the percent excess risk explained
      (%ERE) by comorbidities and nutritional indicators in incident maintenance
      hemodialysis patients. METHODS:: Prospective cohort of 413 adult patients (165
      women, 248 men, 299 <60 years and 114 ?60 years) with <6 months (82% <3 months)
      on dialysis enrolled in PROHEMO in Salvador, Brazil. Low and high handgrip
      strength groups were based on sex-age-specific cutoffs (17.8 kg for women <60
      years, 13.8 kg for women ?60 years, 29.5 kg for men <60 years, and 21.9 kg for
      men ?60 years). We used Cox regression to estimate the mortality hazard ratio.
      The %ERE was determined by the equation (HR1 - HR2)/(HR1 - 1) * 100, in which HR1
      represented the hazard ratio in a model with a smaller number of covariates and
      HR2 represented the hazard ratio in a subsequent model with the inclusion of new
      covariates plus the variables included in the previous model. RESULTS:: The
      mortality hazard ratio comparing low and high handgrip strength was 2.58 (95%
      confidence interval: 1.73, 3.85) in the model with sociodemographic factors and
      vintage and 2.25 (95% confidence interval: 1.49, 3.43) with addition of
      comorbidities, corresponding to a %ERE of 21%. The hazard ratio was 1.98 (95%
      confidence interval: 1.29, 3.06) after addition of nutritional indicators
      corresponding to %ERE of 38%. Results stratified by age and gender followed
      similar patterns. CONCLUSION:: These results provide support for the assessment
      of handgrip strength in all maintenance hemodialysis patients for early
      identification of those who may require special care to improve nutritional
      status and survival.

PMID- 30200793
TI  - Unexpected middle cerebral artery peak systolic velocity values in the normal
      fetal population. Are they a matter of concern?
AB  - OBJECTIVE: The aim of this study was to investigate in the fetus the relationship
      between unexpected high middle cerebral artery peak systolic velocity (middle
      cerebral artery (MCA) peak systolic velocity (PSV)) values and hemoglobin (Hgb)
      levels in normal pregnancies without conditions leading to fetal anemia. MATERIAL
      AND METHODS: This was a prospective study of 922 singleton low-risk pregnant
      women attending the maternity of La Fe Hospital between 35 and 41 weeks. Multiple
      pregnancies and pregnancies with growth restriction, smallness, macrosomia or
      conditions leading to fetal anemia were excluded. During each examination, a
      biometry and a Doppler examination of the umbilical artery pulsatility index
      (umbilical artery (UA) pulsatility index (PI)), MCA PI and MCA PSV were
      performed. MCA PSV was converted into multiples of median (MoM), and birth weight
      (BW) into centiles adjusting for gender. All pregnancies delivered in a 2-week
      interval since examination. In order to explain Hgb levels at birth, a
      correlation between MCA PSV MoM and Hgb was performed and Hgb levels of fetuses
      with normal MCA PSV and abnormal MCA PSV were compared, using 1.3 MoM as cut-off
      for mild anemia. Finally, a multivariate linear regression analysis was performed
      including MCA PSV MoM and several Doppler and clinical parameters. RESULTS: The
      univariate analysis showed no correlation between the MCA PSV MoM and the
      umbilical artery Hgb (r2 = 0.026, p = .1237) while a weak correlation was found
      with the umbilical vein Hgb (r2 = 0.0053, p = .027). Also, fetuses with values of
      MCA PSV MoM <1.3 MoM did not differ in terms of artery and vein Hgb with those
      presenting values >1.3 MoM (p = .99 and p = .61, respectively). Finally, both
      prediction models explaining arterial and venous Hgb presented very weak
      predictive accuracies (R Squared: 0.0965 and R Squared: 0.106) indicating a low
      possibility to diagnose fetal anemia in otherwise normal fetuses based on
      clinical and sonographic data. CONCLUSION: In normal pregnancies that are not
      suffering from conditions leading to fetal anemia, unexpected high MCA PSV values
      do not necessarily reflect the presence of this condition. Active management in
      this circumstance might result in unjustified higher rates of labor induction and
      operative delivery.

PMID- 30200794
TI  - Rotation thromboelastometry (ROTEM) enables improved outcomes in the pediatric
      trauma population.
AB  - Objective We evaluated the role of rotation thromboelastometry (ROTEM) in
      managing acute traumatic coagulopathy in pediatric patients with trauma. Methods
      A retrospective cohort of pediatric patients with trauma from six institutes was
      studied during a 10-year period from 2007 to 2017. The associations between ROTEM
      guided, goal-directed coagulation therapy and clinical outcomes were determined.
      Results Three hundred thirty-two pediatric patients (age < 15 years) who were
      treated with ROTEM-guided, goal-directed coagulation therapy were matched to 332
      control pediatric patients with conventional plasmatic coagulation tests. The
      ROTEM protocol was associated with a significant reduction in the interval for
      admission to acute traumatic coagulopathy treatment, less plasma transfusions in
      the first 24 hours of admission, and a favorable coagulopathy recovery.
      Furthermore, the median number of total hospital days was significantly shorter
      for patients who had the ROTEM protocol than for control patients. Conclusions
      There are significant favorable outcomes, including rapid acute traumatic
      coagulopathy treatment and a lower 24-hour blood product requirement, following
      ROTEM-guided, goal-directed coagulation therapy among pediatric patients with
      blunt trauma.

PMID- 30200795
TI  - Health-related quality-of-life, work productivity, and economic burden among
      patients with Parkinson's disease in Japan.
AB  - AIMS: This study aimed to characterize the burden of Parkinson's disease (PD) by
      examining health-related quality-of-life (HRQoL), impairments to work
      productivity and daily activities, healthcare resource use, and associated costs
      among Japanese patients with PD. MATERIALS AND METHODS: This retrospective cross
      sectional study used data from the 2009-2014 Japan National Health and Wellness
      Survey (NHWS) (n = 144,692). HRQoL (Short Form 36-Item Health Survey version 2),
      impairments to work productivity and daily activities (Work Productivity and
      Activity Impairment Questionnaire), healthcare resource utilization, and annual
      costs were compared between respondents with PD (n = 133) and controls without PD
      (n = 144,559). The effect of PD on outcomes was estimated using propensity score
      weighting and multivariable regression models. RESULTS: HRQoL was lower in
      patients with PD compared to the control group, with reduced physical (41.3 vs
      51.3) and mental (35.7 vs 45.4) component summary scores and health state utility
      scores (0.62 vs 0.77; p < .001 for all). Patients with PD also reported higher
      levels of absenteeism (19.3% vs 3.3%), presenteeism (45.2% vs 18.5%), overall
      work impairment (52.8% vs 20.3%), and activity impairment (49.6% vs 20.8%) than
      controls without PD (p < .001 for all). In addition, patients with PD had higher
      healthcare resource utilization, direct (Y3,856,921/$37,994 vs Y715,289/$7,046),
      and indirect (Y2,573,938/$25,356 vs Y902,534/$8,891) costs compared with controls
      without PD (p < .001 for both). LIMITATIONS: Data were cross-sectional and did
      not allow for causal inferences. Although the NHWS demographically represents the
      Japanese adult population, it is unclear whether it adequately represents the
      adult population with PD in Japan. CONCLUSIONS: PD was associated with poorer
      HRQoL, greater work productivity loss, and higher direct and indirect costs. The
      findings suggest that an unmet need exists among patients with PD in Japan.
      Improving PD treatment and management could benefit both patients and society.

PMID- 30200796
TI  - Large hepatocellular carcinomas: treatment with transarterial chemoembolization
      alone or in combination with percutaneous cryoablation.
AB  - PURPOSE: To evaluate the safety and efficacy of transarterial chemoembolization
      (TACE) combined with cryoablation (TACE-cryoablation) in large (main tumor >=5 cm
      in diameter) hepatocellular carcinomas (HCCs). METHODS: From January 2010 to
      December 2015, 56 lesions in 56 patients were treated with combination therapy
      via a single TACE session followed by one to three percutaneous cryoablation
      sessions twice a week (TACE-cryoablation group). A total of 54 lesions in 54
      patients were treated with TACE alone for two to six sessions once a month (TACE
      group). The decision between TACE and TACE cryoablation was based on patient
      choice. Outcomes of patients in two groups were compared according to the largest
      tumor diameter (subgroup): Group A (5 cm <= tumor <10 cm), Group B (10 cm <=
      tumor <15 cm), and Group C (tumor >=15 cm). RESULTS: The mean number of
      cryoablation sessions per patient was 2.3 (range: 1-6). Within Group B, TACE
      cryoablation significantly improved survival compared with TACE alone (11.0 vs
      6.0 months; p = .008). This was also seen in Group C (8.0 vs 5.0 months; p =
      .001). However, no significant difference was noted in Group A (17.0 vs 13.0
      months; p = .674). The complications related to TACE were comparable between the
      two groups. Two adverse events of grade 3 - 4 related to cryoablation occurred in
      two patients (3.6%). The independent prognostic factors for survival included:
      TACE cryoablation, AFP level, main tumor size and extrahepatic metastasis.
      CONCLUSIONS: TACE-cryoablation may improve overall survival in patients with HCC
      who presented with a tumor diameter >=10 cm, with minimal complications, when
      compared with TACE alone.

PMID- 30200797
TI  - Result of modified Outerbridge-Kashiwagi procedure for elbow flexion contractures
      in brachial plexus birth injury.
AB  - : We report the results of ten consecutive patients who had correction of an
      elbow flexion contracture of greater than 30 degrees  in brachial plexus birth
      injury using a modified Outerbridge-Kashiwagi procedure. All patients had minimum
      23-month follow-up. Pre- and post-operative elbow range of motion and DASH scores
      were recorded in all patients. The operative technique for the procedure and post
      operative course is discussed. Surgery was supplemented by botulinum toxin
      injection into the biceps brachii muscle in most cases. The average age at
      surgery was 14 years 10 months. The initial plexus lesion was global in eight
      patients and upper in two. Pre-operative flexion contractures averaged 51 degrees
      (range 35 to 60) and post-operative averaged 21 degrees  (range 15 to 30). Of
      these patients, one had no change in active flexion, four had loss of active
      flexion, and five had gain of active flexion. All ten patients were satisfied
      with their results and stated that they would recommend the procedure to other
      patients. LEVEL OF EVIDENCE: IV.

PMID- 30200798
TI  - The effect of mean annual temperature on the incidence of distal radial
      fractures.
AB  - We investigated the relationship between the incidence of distal radial fractures
      and mean annual temperature. Data for all adult patients presenting to our unit
      with a distal radial fracture from 2007-2014 were analysed. Incidence rates were
      compared with meteorological records. A Poisson regression model was used to
      analyse trends. Distal radial fractures were sustained by 8831 adults. The only
      significant change in fracture incidence occurred in 2010, in women only. This
      was the coldest year in the United Kingdom for over 20 years. Analysis by age
      bands during 2010 showed fracture incidences were significantly higher for women
      aged 40-69 with a higher percentage of injuries occurring in the street. These
      women are likely to remain mobile during bad weather but frequently have
      underlying osteoporosis. Falls prevention programmes should address this group
      with specific strategies. Simple measures, such as walking aids, appropriate
      footwear and avoidance of non-essential travel in slippery conditions, may reduce
      risk. Level of evidence: IV.

PMID- 30200799
TI  - Phase contrast mapping MRI measurements of global cerebral blood flow across
      different perfusion states - A direct comparison with 15O-H2O positron emission
      tomography using a hybrid PET/MR system.
AB  - Phase-contrast mapping (PCM) magnetic resonance imaging (MRI) provides easy
      access non-invasive quantification of global cerebral blood flow (gCBF) but its
      accuracy in altered perfusion states is not established. We aimed to compare
      paired PCM MRI and 15O-H2O positron emission tomography (PET) measurements of
      gCBF in different perfusion states in a single scanning session. Duplicate
      combined gCBF PCM-MRI and 15O-H2O PET measurements were performed in the resting
      condition, during hyperventilation and after acetazolamide administration (post
      ACZ) using a 3T hybrid PET/MR system. A total of 62 paired gCBF measurements were
      acquired in 14 healthy young male volunteers. Average gCBF in resting state
      measured by PCM-MRI and 15O-H2O PET were 58.5 +/- 10.7 and 38.6 +/- 5.7 mL/100
      g/min, respectively, during hyperventilation 33 +/- 8.6 and 24.7 +/- 5.8 mL/100
      g/min, respectively, and post-ACZ 89.6 +/- 27.1 and 57.3 +/- 9.6 mL/100 g/min,
      respectively. On average, gCBF measured by PCM-MRI was 49% higher compared to 15O
      H2O PET. A strong correlation between the two methods across all states was
      observed (R2 = 0.72, p < 0.001). Bland-Altman analysis suggested a perfusion
      dependent relative bias resulting in higher relative difference at higher CBF
      values. In conclusion, measurements of gCBF by PCM-MRI in healthy volunteers show
      a strong correlation with 15O-H2O PET, but are associated with a large and non
      linear perfusion-dependent difference.

PMID- 30200800
TI  - Efficacy and safety of yttrium-aluminium garnet (YAG) laser vitreolysis for
      vitreous floaters.
AB  - OBJECTIVE: To examine the efficacy and safety of yttrium-aluminium garnet (YAG)
      laser vitreolysis for the treatment of vitreous floaters. METHODS: Consecutive
      adult patients with symptomatic vitreous floaters who attended Chongqing General
      Hospital from April to December 2016 were included in this prospective study.
      Patients had >3 mm between the vitreous opacity and retina/lens and acceptable
      quality peri-papillary Optical Coherence Tomography (OCT) images (i.e., signal
      strength >=5). Those with history of glaucoma, severe cataracts, vitreous
      haemorrhages, retinal holes and/or macular disease were excluded from the study.
      Best corrected visual acuity (BCVA) and non-contact intraocular pressure (IOP)
      were measured before and for up to 6 months post-YAG laser vitreolysis. Anterior
      segment photography and peripapillary retinal nerve fibre layer (RNFL) measured
      by OCT were taken before and 6 months post-procedure. Questionnaires on patient
      satisfaction were completed 6 months post-procedure. RESULTS: No statistically
      significant differences in BCVA and IOP were observed before or after treatment.
      Anterior segment photography showed that vitreous opacities partially or
      completely disappeared after YAG laser treatment. The thickness of RNFL in four
      directions (upper, below, nasal and temporal) was not statistically significant
      different before or 6 months after the procedure. 75% patients reported
      significant improvement and 25% reported moderate improvement. CONCLUSION: The
      results of this study conducted in a cohort of 30 Chinese patients showed that
      YAG laser vitreolysis was a well-tolerated and effective treatment for vitreous
      floaters. Randomised, controlled trials involving large numbers of participants
      monitored over an extended follow up period are required to confirm these
      results.

PMID- 30200801
TI  - Dentoskeletal and soft tissue changes associated with miniscrew anchorage in
      customized lingual orthodontics.
AB  - Objectives The goal of this study was to analyze skeletal, dental, and soft
      tissue changes of patients treated with customized lingual systems and to
      evaluate the clinical effectiveness of miniscrew anchorage. Methods Nine upper
      first premolar extraction patients who were treated with customized lingual
      appliances were included in this study. Miniscrews were used for reinforcement of
      molar anchorage. Cephalometric films and study models were obtained before
      treatment (T1), after alignment (T2), and after treatment (T3). Treatment effects
      were analyzed by cephalometric radiographs and study models. Results The upper
      anterior teeth were retracted significantly at T2 and T3 (4.41 +/- 4.14 mm and
      5.51 +/- 2.48 mm, respectively). During space closure, the upper first molars
      showed slight mesial movement (1.50 +/- 1.97 mm). The intercanine width of the
      upper arch increased at T2 (1.59 +/- 1.81 mm), but decreased at T3 (0.11 +/- 1.00
      mm). The sella-nasion-A, A-nasion-B, and mandibular plane angles were not
      significantly changed at T3. The upper lip showed continuous retraction at both
      T2 and T3 (1.40 +/- 1.46 mm and 2.32 +/- 2.48 mm, respectively). Conclusions By
      using miniscrew anchorage for lingual orthodontics, patients' dental and soft
      tissue changes considerably improved and molar anchorage was reinforced.

PMID- 30200802
TI  - LAMA5 promotes human umbilical vein endothelial cells migration, proliferation,
      and angiogenesis and is decreased in preeclampsia.
AB  - OBJECTIVE: Preeclampsia (PE) is currently thought to associated with oxidative
      stress and vascular endothelial dysfunction. LAMA5 is associated with the cell
      migration, proliferation, and vascular endothelial function. The aims of this
      study are to investigate the expression patterns of LAMA5 in normal and PE
      pregnancies, as well as evaluating the effects of LAMA5 on human umbilical vein
      endothelial cells (HUVECs) function. METHODS: LAMA5 expression levels were
      examined by reverse-transcriptase polymerase chain reaction (RT-PCR) and further
      confirmed by western blot and immunofluorescence. Cell proliferation and
      apoptosis were measured by CCK-8 assay and flow cytometry respectively. Cell
      migration was assessed by transwell migration assay. RESULTS: LAMA5 expression
      levels of vascular endothelial cells in PE placentas was significantly decreased
      than that in normal placentas. LAMA5 small-interfering RNA (siRNA) transfection
      and hypoxia/reoxygenation (H/R) treatments resulted in decreased proliferation,
      migration, and vascular formation ability of HUVECs but increased HUVECs
      apoptosis. Down-regulated LAMA5 could inhibit the protein expression of the PI3K
      downstream p-AKT and p-MTOR. CONCLUSIONS: Down-regulated LAMA5 is associated with
      PE placenta and restrained HUVECs proliferation, migration, and angiogenesis
      through PI3K-AKT-MTOR signaling pathways.

PMID- 30200803
TI  - The protective effects of rapamycin on cell autophagy in the renal tissues of
      rats with diabetic nephropathy via mTOR-S6K1-LC3II signaling pathway.
AB  - BACKGROUND: Previous studies have shown that podocyte autophagy is an important
      trigger for proteinuria and glomerulosclerosis. The mammalian rapamycin target
      protein (mTOR) occupies a pivotal position in the autophagy pathway. In this
      study, we planned to clarify the mechanism of mTOR regulation of podocyte
      autophagy and the effect of rapamycin (RAPA). METHODS: All rats were randomly
      divided into normal control group (n = 8), DN group (n = 8), and RAPA group (n =
      8). Blood and urine samples were collected at the 4th, 8th, and 12th weeks of the
      experiment. The serum creatinine (Scr), urine volume levels, and the 24 h urine
      protein (UP) levels were examined. The nephrin, podocin, mTOR, ribosomal S6
      kinase 1 (S6K1), and autophagy marker light chain 3 (LC3II) expression levels
      were evaluated by immunohistochemistry, quantitative PCR, and immunoblotting.
      RESULTS: The urine volume, 24 h UP, and Scr of the DN and RAPA groups increased
      significantly compared with the NC group (p < .05). Nephrin and podocin
      expression was decreased in the kidney tissues of the DN and RAPA groups compared
      with the NC group (p < .05). The expression levels of mTOR and S6K1 increased and
      LC3II expression decreased in the renal tissues of the DN and RAPA groups
      compared with the NC group (p < .05). After RAPA treatment, all the above indexes
      were improved compared with the DN group (p < .05), but were significantly
      abnormal compared with the NC group (p < .05). CONCLUSION: The proteinuria and
      kidney function had improved after RAPA treatment. These results confirmed that
      RAPA specifically binds to mTOR kinase, and inhibits mTOR activity, thereby
      regulating the pathological autophagic process.

PMID- 30200805
TI  - A green chemical oligomerization of phloroglucinol induced by plasma as novel
      alpha-glucosidase inhibitors.
AB  - A new facile method was developed for simple green synthesis of methylene-bridged
      phloroglucinol oligomers using nonthermal dielectric barrier discharge (DBD)
      plasma in methanolic solution. The chemical structures of these newly generated
      oligomers 2-5 were determined by interpretation of the spectroscopic data, and
      the inhibitory activity toward alpha-glucosidase of all isolates was evaluated.
      The unusual phloroglcuinol pentamer 5 connected by four methylene linkages showed
      a much higher potential inhibitory effect against alpha-glucosidase than the
      other generated oligomers 2-4 and appeared to be a promising lead for development
      as a potential antidiabetic agent. Abbreviations: T2DM, type2 diabetes mellitus;
      DBD, dielectric barrier discharge; HPLC, high-performance liquid chromatography;
      IC50, 50% inhibition concentration; NMR, nuclear magnetic resonance; FABMS,
      fastatom bombardment mass spectrometry.

PMID- 30200804
TI  - LncRNA CASC11 promoted gastric cancer cell proliferation, migration and invasion
      in vitro by regulating cell cycle pathway.
AB  - In this study, we aimed to investigate the effects of lncRNA CASC11 on gastric
      cancer (GC) cell progression through regulating miR-340-5p and cell cycle
      pathway. Expressions of lncRNA CASC11 in gastric cancer tissues and cell lines
      were determined by qRT-PCR. Differentially expressed lncRNAs, mRNAs and miRNAs
      were screened through microarray analysis. The relationship among CASC11, CDK1
      and miR-340-5p was predicted by TargetScan and validated through dual luciferase
      reporter assay. Western blot assay examined the protein level of CDK1 and several
      cell cycle regulatory proteins. GO functional analysis and KEGG pathway analysis
      were used to predict the association between functions and related pathways. Cell
      proliferation was determined by CCK-8 assays. Cell apoptosis and cell cycle were
      detected by flow cytometry assay. CASC11 was highly expressed in GC tissues and
      cell lines. Knockdown of CASC11 inhibited GC cell proliferation, promoted cell
      apoptosis and blocked cell cycle. KEGG further indicated an enriched cell cycle
      pathway involving CDK1. QRT-PCR showed that miR-340-5p was down-regulated in GC
      cells tissues, while CDK1 was up-regulated. Furthermore, CASC11 acted as a sponge
      of miR-340-5p which directly targeted CDK1. Meanwhile, miR-340-5p overexpression
      promoted GC cell apoptosis and induced cell cycle arrest, while CDK1
      overexpression inhibited cell apoptosis and accelerated cell cycle. Our study
      revealed the mechanism of CASC11/miR-340-5p/CDK1 network in GC cell line, and
      suggested that CASC11 was a novel facilitator that exerted a biological effect by
      activating the cell cycle signaling pathway. This finding provides a potential
      therapeutic target for GC.

PMID- 30200806
TI  - Unveiling the RNA World.

PMID- 30200808
TI  - An analysis of nursing students' ethical conflicts in a hospital.
AB  - BACKGROUND: Education can be taken as a key factor in transmission of a value
      tradition in healthcare. In professional and educational contexts, transmission
      of values appears to be a kind of guarantee for an occupational group's
      professional identity, awareness and ethical integrity. Given the positives of
      such transmission of value traditions, one can also pay attention to conflicts
      between the professional tradition and individuals who are brought into that
      tradition. OBJECTIVES: How does mediation of value tradition in healthcare
      education appear out of the students' perspective based on their own narratives?
      Research design and participants: Students' texts were analysed through a
      combination of contrastive discourse analysis and sociohistorical description and
      then evaluated from an ethical perspective. Data were collected from the annual
      electronic feedback given by students after their clinical practice at a
      University Hospital. Ethical considerations: Organizational approval was
      received. Information about the voluntary nature of participation was a part of
      the feedback tool. FINDINGS: The analysis points to the fact that there is a
      definite theme in the students' experiences that both the previous research has
      neglected and that stands in conflict with the current tradition of healthcare
      education in Finland. That theme can be summarized in the experience of 'losing
      one's identity', and it is expressed in a request to experience of 'losing one's
      identity' and it is expressed in a request to have a right to 'use one's own
      name' also as a healthcare professional. DISCUSSION AND CONCLUSION: Being
      addressed by one's name is to make the person directly involved and responsible,
      realizing that that person's perspective is of importance to the way the world
      is. We argue that this theme (my name) is of ethical importance and could have
      empowering potentiality when used in an ethically sound way.

PMID- 30200807
TI  - Circadian Dysregulation: The Next Frontier in Obstructive Sleep Apnea Research.
AB  - OBJECTIVE: To review the effects of the circadian clock on homeostasis, the
      functional interaction between the circadian clock and hypoxia-inducible factors,
      and the role of circadian dysregulation in the progression of cardiopulmonary
      disease in obstructive sleep apnea (OSA). DATA SOURCES: The MEDLINE database was
      accessed through PubMed. REVIEW METHODS: A general review is presented on
      molecular pathways disrupted in OSA, circadian rhythms and the role of the
      circadian clock, hypoxia signaling, crosstalk between the circadian and hypoxia
      systems, the role of the circadian clock in cardiovascular disease, and
      implications for practice. Studies included in this State of the Art Review
      demonstrate the potential contribution of the circadian clock and hypoxia in
      animal models or human disease. CONCLUSIONS: Molecular crosstalk between the
      circadian clock and hypoxia-inducible factors has not been evaluated in disease
      models of OSA. IMPLICATIONS FOR PRACTICE: Pediatric OSA is highly prevalent and,
      if left untreated, may lead to cardiopulmonary sequelae. Changes in inflammatory
      markers that normally demonstrate circadian rhythmicity are also seen among
      patients with OSA. Hypoxia-inducible transcription factors interact with core
      circadian clock transcription factors; however, the interplay between these
      pathways has not been elucidated in the cardiopulmonary system. This gap in
      knowledge hinders our ability to identify potential biomarkers of OSA and develop
      alternative therapeutic strategies. A deeper understanding of the mechanisms by
      which OSA impinges on clock function and the impact of clock dysregulation on the
      cardiopulmonary system may lead to future advancements for the care of patients
      with OSA. The aim of this review is to shed light on this important clinical
      topic.

PMID- 30200809
TI  - The Association of Handgrip Strength and Mortality: What Does It Tell Us and What
      Can We Do With It?
AB  - The relationship between grip strength and mortality is often used to underscore
      the importance of resistance exercise in physical activity guidelines. However,
      grip strength does not appear to appreciably change following traditional
      resistance training. Thus, grip strength could be considered reflective of
      strength independent of resistance exercise. If true, grip strength is not
      necessarily informing us of the importance of resistance exercise as an adult,
      but potentially highlighting inherent differences between individuals who are
      stronger at "baseline" compared to their weaker counterpart. The purpose of this
      article is to discuss: (1) potential factors that may influence grip strength and
      (2) hypothesize strategies that may be able to influence grip strength and
      ultimately attain a higher baseline level of strength. Although there appears to
      be a limited ability to augment grip strength as an adult, there may be critical
      periods during growth/development during which individuals can establish a higher
      baseline. Establishing a high baseline of strength earlier in life may have long
      term implications related to mortality and disease.

PMID- 30200810
TI  - Assessment and Treatment of Behavioral Disorders in Children with Hearing Loss: A
      Systematic Review.
AB  - Objective There is evidence that children who are deaf and hard of hearing (DHH)
      have a higher incidence of behavioral disorders. Assessment of behavioral health
      in this population is often complicated by language developmental delays, which
      may result in unrecognized and untreated behavioral problems. The purpose of this
      study is to assess the association of behavioral disorders among children who are
      DHH and to explore behavioral interventions for children in this population. Data
      Sources PubMed, CINALH, PsychINFO, and Web of Science. Review Methods Search
      terms included the following: problem behavior, child behavior
      disorders/diagnosis, child behavior disorders/psychology coupled with hearing
      loss, cochlear implants, hearing aids, or deafness. Studies from the last 30
      years (1985-2016) were included. The articles were reviewed independently by 3
      reviewers. Results Thirty-six articles met criteria. There was an association
      between internalizing behaviors and hearing loss among children, which may
      persist after cochlear implantation. These problems may be more pronounced for
      children with additional disabilities. Conduct and hyperactivity disorders as
      well as emotional and executive function problems among children who are DHH may
      be related to poor language development. There was limited evidence regarding
      interventions to address the behavioral disorders of DHH children. Conclusions
      There is a significant body of evidence demonstrating behavioral problems among
      DHH children but a lack of clear understanding of the mechanisms involved. There
      is limited evidence on interventions to address the behavioral problems of DHH
      children. Future research is warranted to mitigate the long-term effects of
      disruptive behavior among these children.

PMID- 30200811
TI  - The influence of individualistic and collectivistic morality on dementia care
      choices.
AB  - BACKGROUND: If collectivistic-oriented family carers choose professional care for
      dependents with dementia, they risk being stigmatised as failing their
      obligation. This may influence dementia care choices. RESEARCH QUESTION: How may
      individualistic and collectivistic values influence choices in dementia care?
      METHOD: Qualitative design with in-depth interviews with a total of 29 nurses, 13
      family members in Norway and the Balkans and 3 Norwegian dementia care
      coordinators. A hermeneutic content-focused analysis was used. Ethical
      considerations: Ethical approval was obtained from the Regional Ethics Committee
      for Research, South-Eastern Norway, and the nursing homes' leadership. FINDINGS:
      Family domain reasons why institutionalisation of dependents with dementia was
      seen as a last resort: obligation towards family members, particularly parents;
      worry about other family members' reactions and inability to cope with the care
      for the person with dementia. Social domain reasons: feelings of shame and stigma
      regarding dementia, particularly in connection with institutionalisation of
      family members. DISCUSSION: Children's obligation towards their parents is an
      important aspect of the morality of collectivistic societies. Institutionalising
      parents with dementia may cause feelings of guilt and shame and worry about being
      stigmatised and ostracised. To avoid blame and rejection, caregiver(s) try to
      keep the fact that family members have dementia 'in the family'. The decision to
      accept professional healthcare for dependents with severe dementia or have them
      admitted to a geriatric institution was postponed as long as possible.
      CONCLUSION: Family care morality may constitute a significant barrier against
      seeking professional help for persons with dementia, a barrier based on the
      expectation that the family will care for their old, even when suffering from
      severe dementia. Hence, stigma and shame may significantly affect the provision
      of care. Culturally tailored information may encourage family carers to seek
      professional help before the disruptive influence of the disease makes
      institutionalisation the only feasible option.

PMID- 30200812
TI  - Virtual Functional Endoscopic Sinus Surgery Simulation with 3D-Printed Models for
      Mixed-Reality Nasal Endoscopy.
AB  - The surgeon's knowledge of a patient's individual anatomy is critical in skull
      base surgery. Trainees and experienced surgeons can benefit from surgical
      simulation; however, current models are expensive and impractical for widespread
      use. In this study, we report a next-generation mixed-reality surgical simulator.
      We segmented critical anatomic structures for 3-dimensional (3D) models to
      develop a modular teaching tool. We then developed a navigation tracking system
      utilizing a 3D-printed endoscope as a trackable virtual-reality (VR) controller
      and validated the accuracy on VR and 3D-printed skull models within 1 cm. We
      combined VR and augmented-reality visual cues with our 3D physical model to
      simulate sinus endoscopy and highlight segmented structures in real time. This
      report provides evidence that a mixed-reality simulator combining VR and 3D
      printed models is feasible and may prove useful as an educational tool that is
      low cost and customizable.

PMID- 30200813
TI  - Symptomatic Subclavian Steal During Pregnancy in a Woman Status Post Coarctation
      Repair in Infancy.
AB  - A 24-year-old woman with a history of coarctation repair by subclavian flap
      aortoplasty presented at 15 weeks' gestation with transient episodes of vision
      loss. She was diagnosed with subclavian steal syndrome and underwent left carotid
      artery to subclavian artery bypass at 17 weeks' gestation. She has had no
      recurrence of symptoms at ten months of postoperative follow-up. Despite the
      anatomic substrate for subclavian steal in patients with this type of surgical
      repair, neurologic symptoms are uncommon. It is possible that the pregnancy
      induced fall in systemic vascular resistance triggered symptoms in this
      previously asymptomatic patient.

PMID- 30200814
TI  - The effect of unloader knee braces on medial meniscal strain.
AB  - BACKGROUND: A medial meniscal tear is a common knee injury, especially following
      an anterior cruciate ligament injury. Decreasing the compressive force on the
      medial meniscus during dynamic activities using an unloader knee brace could
      reduce meniscal strain, effectively reducing injury risk and/or severity.
      OBJECTIVES: To investigate the efficacy of two unloader knee braces on medial
      meniscus strain during dynamic activities in intact & deficient anterior cruciate
      ligament states. STUDY DESIGN: Combined in vivo/in vitro study. METHODS: In vivo
      knee kinematics and muscle force profiles from a healthy individual performing
      single/doubleleg squats and walking motions were simulated on 10 cadaveric
      specimens using a dynamic knee simulator system. Simulations were performed on
      knees in unbraced and braced scenarios, with and without the anterior cruciate
      ligament. Anterior and posterior medial meniscal strains were measured. RESULTS:
      Two different braces each showed a significant reduction in the posteromedial
      meniscal strain ( p ? 0.01) in an intact anterior cruciate ligament state.
      Neither brace mirrored this result for the anteromedial strain ( p > 0.05). In
      the deficient anterior cruciate ligament state, the braces had no significant
      effect on strain ( p > 0.05). CONCLUSION: Two unloader knee braces effectively
      reduced strain in the medial meniscus with an intact anterior cruciate ligament
      during dynamic activities. Neither brace made a significant reduction in strain
      for anterior cruciate ligament-deficient knees. Clinical relevance Unloader knee
      braces could be used to reduce the medial meniscus strain following meniscal
      surgery and during rehabilitation in patients with an isolated medial meniscus
      injury. However, these braces cannot be recommended for this purpose in patients
      with an anterior cruciate ligament deficiency.

PMID- 30200816
TI  - Medical Treatment for Epistaxis in Hereditary Hemorrhagic Telangiectasia: A Meta
      analysis.
AB  - Objectives The aim of this study (PROSPERO ID: CRD42017081952) was to evaluate
      medical treatment for epistaxis from hereditary hemorrhagic telangiectasia (HHT).
      Data Sources PubMed, Embase, Scopus, and Cochrane Library databases were
      interrogated from their inceptions to November 2017. Review Methods Randomized
      clinical trials comparing medical treatment with placebo for epistaxis of HHT
      were included. We used a random-effects model to synthesize overall effects.
      Heterogeneity was evaluated with the I2 statistic. Results Eight studies were
      identified after systematic searching. The use of bevacizumab (BV), tranexamic
      acid, and estrogen, regardless of the route of administration, had no significant
      influence on frequency of episodes. Tamoxifen was superior to placebo in both
      frequency and severity of epistaxis. For duration of epistaxis, nasal spray BV,
      oral or nasal spray tranexamic acid, and nasal spray estrogen had no significant
      differences versus placebo, but patients receiving submucosal BV showed lower
      duration of epistaxis (mean difference: -219.00 min/mo, 95% CI: -271.90 to 
      166.10). Medical treatment for HHT had no significant changes of mean hemoglobin
      concentration (pooled mean difference: -0.23 mg/dL, 95% CI: -0.65 to 0.20, I2 =
      0%) or quality of life (pooled standardized mean difference: 0.07, 95% CI: -0.16
      to 0.30, I2 = 0%). Conclusions Only limited evidence provides a benefit on
      frequency of epistaxis by treatment with tamoxifen and duration of epistaxis by
      treatment with submucosal BV among patients with HHT. Mean hemoglobin
      concentration and quality of life were not influenced by medical treatment.

PMID- 30200815
TI  - Health-related quality of life and associated factors in adults living with HIV
      in Rwanda.
AB  - In Rwanda, as in other sub-Saharan African (SSA) countries, life expectancy of
      people living with HIV (PLWH) has increased dramatically as a result of combined
      antiretroviral therapy (cART). People living with HIV can now live longer but
      with increasing rates of non-communicable diseases (NCDs). Thus, prevention of
      NCD comorbidities in PWLHI is crucial to maintain and gain health-related
      benefits and to maximise the health-related quality of life (HRQOL) in the long
      term management of PLWH. This study determines the association between physical
      and mental health-related dimensions of quality of life (QOL) with behavioural
      and biological risk factors, after controlling socio-demographic and HIV-related
      factors in adults living with HIV in Rwanda. A cross-sectional study using the
      WHO STEPwise approach and Kinyarwanda version of the MOS-HIV Health Survey, risk
      factors for NCDs and HRQOL were analysed for 794 PLWH, both HIV+ on ART and ART
      naive. Multiple regression analysis was used to examine the relationship between
      CMD risk factors and physical health and mental health summary scores. A total of
      794 participants were interviewed. The mean age of the sample was 37.9 (+/-10.8)
      years and the majority of the participants were women (n = 513; 64.6%). About
      16.2% reported daily smoking, 31.4% reported harmful alcohol use and 95% reported
      insufficient consumption of vegetables and fruits while 26.1% reported being
      physically inactive. 18.4% were overweight 43.4% had abdominal obesity, i.e.
      waist-hip-ratio (WHR) >=0.95 in males and 0.85 in females. High blood pressure
      (HBP), i.e. systolic blood pressure (SBP) of >=140 mmHg, or diastolic blood
      pressure (DBP) >=90 mmHg was 24.4%. The results reveal that mean physical health
      summary and mental health summary score values were 63.96 +/- 11.68 and 53.43 +/-
      10.89, respectively. While participants indicated that tobacco users and those
      who had abdominal obesity reported poor mental HRQOL, physical inactivity and
      hypertension have a negative impact on physical HRQOL. In addition, certain socio
      demographic and HIV-related variables - specifically being unmarried, lack of HIV
      disclosure and low CD4 count (less 350 cell counts /mm3) - were associated with
      significantly lower mental and physical dimensions of quality of life. The
      results of this study reveal that behavioural and biological risk factors for
      NCDs were significantly associated with a lower HRQOL. These research findings
      also suggest that the assessment of the association between behavioural and
      biological risk factors for NCDs and a HRQOL provides opportunities for targeted
      counselling and secondary prevention efforts, so that health care providers can
      implement strategies that have a significant impact on the HRQOL.

PMID- 30200817
TI  - Methyl-beta-cyclodextrin potentiates the BITC-induced anti-cancer effect through
      modulation of the Akt phosphorylation in human colorectal cancer cells.
AB  - Methyl-beta-cyclodextrin (MbetaCD) is an effective agent for the removal of
      plasma membrane cholesterol. In this study, we investigated the modulating
      effects of MbetaCD on the antiproliferation induced by benzyl isothiocyanate
      (BITC), an ITC compound mainly derived from papaya seeds. We confirmed that
      MbetaCD dose-dependently increased the cholesterol level in the medium, possibly
      through its removal from the plasma membrane of human colorectal cancer cells.
      The pretreatment with a non-toxic concentration (2.5 mM) of MbetaCD significantly
      enhanced the BITC-induced cytotoxicity and apoptosis induction, which was
      counteracted by the cholesterol supplementation. Although BITC activated the
      phosphoinositide 3-kinase (PI3K)/Akt pathway, MbetaCD dose-dependently inhibited
      the phosphorylation level of Akt. On the contrary, the treatment of MbetaCD
      enhanced the phosphorylation of mitogen activated protein kinases, but did not
      potentiate their BITC-induced phosphorylation. These results suggested that
      MbetaCD might potentiate the BITC-induced anti-cancer by cholesterol depletion
      and thus inhibition of the PI3K/Akt-dependent survival pathway. Abbreviations:
      CDs: cyclodextrins; MbetaCD: methyl-beta-cyclodextrin; ITCs: isothiocyanates;
      BITC: benzyl isothiocyanate; PI3K: phosphoinositide 3-kinase; PDK1:
      phosphoinositide-dependent kinase-1; MAPK: mitogen activated protein kinase;
      ERK1/2: extracellular signal-regulated kinase1/2; JNK: c-Jun N-terminal kinase;
      PI: propidium iodide; FBS: fatal bovine serum; TLC: thin-layer chromatography;
      PBS(-): phosphate-buffered saline without calcium and magnesium; MEK: MAPK/ERK
      kinase; PIP2: phosphatidylinositol-4,5-bisphosphate; PIP3: phosphatidylinositol
      3,4,5-trisphosphate.

PMID- 30200818
TI  - Ice hockey skating sprints: run to glide mechanics of high calibre male and
      female athletes.
AB  - The skating acceleration to maximal speed transition (sprint) is an essential
      skill that involves substantial lower body strength and effective propulsion
      technique. Coaches and athletes strive to understand this optimal combination to
      improve performance and reduce injury risk. Hence, the purpose of this study was
      to compare body centre of mass and lower body kinematic profiles from static
      start to maximal speed of high calibre male and female ice hockey players on the
      ice surface. Overall, male and female skaters showed similar centre of mass
      trajectories, though magnitudes differed. The key performance difference was the
      male's greater peak forward skating speed (8.96 +/- 0.44 m/s vs the females' 8.02
      +/- 0.36 m/s, p < 0.001), which was strongly correlated to peak leg strength (R2
      = 0.81). Males generated greater forward acceleration during the initial
      accelerative steps, but thereafter, both sexes had similar stride-by-stride
      accelerations up to maximal speed. In terms of technique, males demonstrated
      greater hip abduction (p = 0.006) and knee flexion (p = 0.026) from ice contact
      to push off throughout the trials. For coaches and athletes, these findings
      underscore the importance of leg strength and widely planted running steps during
      the initial skating technique to achieve maximal skating speed over a 30 m
      distance.

PMID- 30200819
TI  - Review: Update on Classical and Atypical Scrapie in Sheep and Goats.
AB  - Scrapie is a naturally occurring transmissible spongiform encephalopathy (TSE) or
      prion disease of sheep and goats. Scrapie is a protein misfolding disease where
      the normal prion protein (PrPC) misfolds into a pathogenic form (PrPSc) that is
      highly resistant to enzymatic breakdown within the cell and accumulates,
      eventually leading to neurodegeneration. The amino acid sequence of the prion
      protein and tissue distribution of PrPSc within affected hosts have a major role
      in determining susceptibility to and potential environmental contamination with
      the scrapie agent. Many countries have genotype-based eradication programs that
      emphasize using rams that express arginine at codon 171 in the prion protein,
      which is associated with resistance to the classical scrapie agent. In classical
      scrapie, accumulation of PrPSc within lymphoid and other tissues facilitates
      environmental contamination and spread of the disease within flocks. A major
      distinction can be made between classical scrapie strains that are readily spread
      within populations of susceptible sheep and goats and atypical (Nor-98) scrapie
      that has unique molecular and phenotype characteristics and is thought to occur
      spontaneously in older sheep or goats. This review provides an overview of
      classical and atypical scrapie with consideration of potential transmission of
      classical scrapie to other mammalian hosts.

PMID- 30200820
TI  - Does Socioeconomic Status Affect Stage at Presentation for Larynx Cancer in
      Canada's Universal Health Care System?
AB  - Objective Diagnosis of laryngeal cancer is dependent on awareness that persistent
      hoarseness needs to be investigated as well as access to an otolaryngologist.
      This study aimed to better classify and understand 3 factors that may lead to
      variability in stage at presentation of laryngeal cancer: (1) socioeconomic
      status (SES), (2) differences in access to health care by location of residence
      (rural vs urban or by province), and (3) access to an otolaryngologist (by
      otolaryngologists per capita). Study Design Registry-based multicenter cohort
      analysis. Setting This was a national study across Canada, a country with a
      single-payer, universal health care system. Subjects All persons 18 years or
      older who were diagnosed with laryngeal cancer from 2005 to 2013 inclusive were
      extracted from the Canadian Cancer Registry (CCR). Methods Ordered logistic
      regression was used to determine the effect of income, age, sex, province of
      residence, and rural vs urban residence on stage at presentation. Results A total
      of 1550 cases were included (1280 males and 265 females). The stage at
      presentation was earlier in the highest income quintile (quintile 5) compared to
      the lower income quintiles (quintiles 1-4) (odds ratio [OR], 0.68; P < .05).
      There was a statistically significant difference in stage at presentation based
      on rural or urban residence within the highest income quintile (OR, 1.73; P <
      .005). Conclusion There is a relationship between SES and stage at presentation
      for laryngeal cancer even in the Canadian universal health care system.

PMID- 30200821
TI  - Single-molecule long-read transcriptome profiling of Platysternon megacephalum
      mitochondrial genome with gene rearrangement and control region duplication.
AB  - Platysternon megacephalum is the sole living representative of the poorly studied
      turtle lineage Platysternidae. Their mitochondrial genome has been subject to
      gene rearrangement and control region duplication, resulting in a unique
      mitochondrial gene order in vertebrates. In this study, we sequenced the first
      full-length turtle (P. megacephalum) liver transcriptome using single-molecule
      real-time sequencing to study the transcriptional mechanisms of its mitochondrial
      genome. ND5 and ND6 anti-sense (ND6AS) forms a single transcript with the same
      expression in the human mitochondrial genome, but here we demonstrated
      differential expression of the rearranged ND5 and ND6AS genes in P. megacephalum.
      And some polycistronic transcripts were also reported in this study. Notably, we
      detected some novel long non-coding RNAs with alternative polyadenylation from
      the duplicated control region, and a novel ND6AS transcript composed of a long
      non-coding sequence, ND6AS, and tRNA-GluAS. These results provide the first
      description of a mtDNA transcriptome with gene rearrangement and control region
      duplication. These findings further our understanding of the fundamental concepts
      of mitochondrial gene transcription and RNA processing, and provide a new insight
      into the mechanism of transcription regulation of the mitochondrial genome.

PMID- 30200822
TI  - Linalool odor stimulation improves heat stress tolerance and decreases fat
      accumulation in nematodes.
AB  - Aromatherapy uses plant essential oils and fragrant ingredients for relaxation,
      sleep assistance, and improvement of restlessness related to dementia. Certain
      aromatic substances increase the life span and stress tolerance of nematodes. We
      investigated effects of exposure to linalool, a linear chain monoterpenic alcohol
      that is present in the essential oils of many plants, and its optical isomer, l
      linalool, in Caenorhabditis elegans. Nematodes were repelled by the odor of both
      linalool and l-linalool; however, linalool odor stimulation decreased fat
      accumulation and increased motility after thermal stress. Analysis of a gene
      deficient mutant revealed that the DAF-16 insulin-signaling pathway, which is
      involved in heat stress tolerance, was enhanced by linalool treatment. Linalool
      stimulation increased the expression of downstream genes such as sod-3 and hsp
      12.6 via DAF-16. We conclude that linalool odor induces a repelling behavior in
      nematodes, improves heat stress tolerance through the DAF-16 signaling pathway,
      and affects fat accumulation.

PMID- 30200823
TI  - Simultaneous collection of the portal and superior vena cava blood in conscious
      rats defined that intestinal epithelium is the major site of glucuronidation, but
      not sulfation and methylation, of quercetin.
AB  - Quercetin is a flavonoid with many physiological effects. Absorbed quercetin is
      rapidly conjugated in the intestinal epithelium and liver. Different positional
      isomers of quercetin conjugates have different physiological properties. However,
      the mechanisms of quercetin conjugation in the intestine are not fully clarified.
      We examined the regioselective quercetin conjugate formation in the intestine
      after oral administration of quercetin glycosides, by simultaneous sampling of
      blood from the portal vein and superior vena cava, and quantifying various
      positional isomers of quercetin glucuronides and sulfates in conscious rats.
      Concentrations of quercetin glucuronides were higher in blood from the portal
      vein than the superior vena cava, showing that glucuronidation mainly occurred in
      the intestine. Such differences were not observed for quercetin sulfates.
      Regioselectivity of the intestinal glucuronidation in quercetin hydroxyl groups
      were 7- >3'- >3- >4'-OH. Quercetin was mainly sulfated on 3'-OH at 30 min, but on
      4'-OH at 240 min.

PMID- 30200824
TI  - Views of nurses and other health and social care workers on the use of assistive
      humanoid and animal-like robots in health and social care: a scoping review.
AB  - BACKGROUND: Robots are introduced in many health and social care settings.
      OBJECTIVES: To provide an overview of the existing evidence related to the views
      of nurses and other health and social care workers about the use of assistive
      humanoid and animal-like robots. METHODS: Using the Joanna Briggs Institute
      guidelines we searched MEDLINE, PUBMED, CINHAL, EMBASE, PsycInfo, Web of Science,
      and IEEE Xplore digital library. Nineteen (19) articles met the criteria for
      inclusion. RESULTS: Health care workers reported mixed views regarding the use of
      robots. They considered an array of tasks that robots could perform; they
      addressed the issue of patient safety and raised concerns about privacy.
      CONCLUSIONS: A limited number of studies have explored the views of health care
      workers about the use of robots. Considering the fast pace with which technology
      is advancing in the care field, it is critical to conduct more research in this
      area. Impact Statement: Robots will increasingly have a role to play in nursing,
      health and social care. The potential impact will be challenging for the
      healthcare workforce. It is therefore important for nurses and other health and
      social care workers to engage in discussion regarding the contribution of robots
      and their impact not only on nursing care but also on future roles of health and
      social care workers.

PMID- 30200825
TI  - Chronic cerebrospinal venous insufficiency, chlamydia and multiple sclerosis.

PMID- 30200826
TI  - Thiosulfate promotes hair growth in mouse model.
AB  - The present study describes the hair growth-promoting effects of sodium
      thiosulfate (STS), a widely used compound, in mice. STS accelerated hair growth
      in the "telogen model", suggesting that it stimulates telogen hair follicles to
      reenter the anagen phase of hair growth. In the same model, STS potentiated hair
      growth in an additive manner with minoxidil (MXD), a drug used for the treatment
      of androgenic alopecia. Furthermore, in the "anagen model", STS promoted hair
      growth, probably by promoting hair follicle proliferation. Since STS elevated the
      skin surface temperature, its hair growth-promoting activity may be partly due to
      vasorelaxation, similar to MXD. In addition, STS is known to generate a gaseous
      mediator, H2S, which has vasorelaxation and anti-inflammatory/anti-oxidative
      stress activities. Therefore, STS and/or provisionally its metabolite, H2S, may
      aid the hair growth process. Collectively, these results suggest that salts of
      thiosulfate may represent a novel and beneficial remedy for hair loss.

PMID- 30200827
TI  - Urinary fibrinogen is elevated in hospitalized patients undergoing angiography.
AB  - Objectives Previously, we found that urinary fibrinogen (Fg) levels were
      positively related to contrast-induced acute renal injury degree in mice.
      Reduction of fibrinogen in heterozygous mice can improve renal function. Here, we
      prospectively observed the variation in urinary Fg levels in patients undergoing
      angiography to determine the relationship between serum creatinine (Scr) and
      serum cystatin C (Cys C) levels. Methods Serum Cys C and urinary Fg levels were
      evaluated by ELISA before and 2, 12, and 24 h after angiography in 115 enrolled
      inpatients. Scr was assessed before and 24 and 48 h after angiography. Data were
      analyzed using ANOVA or Kruskal-Wallis ANOVA and Spearman correlation. Results
      Urinary Fg levels were elevated as early as 2 h after angiography and decreased
      thereafter before returning to baseline levels 24 h after angiography. Urinary Fg
      was correlated with the amount of contrast agent ( r = 0.24, p = 0.036) and the
      presence of diabetes and hypertension ( r = 0.31, r = 0.28, p < 0.05,
      respectively). Urinary Fg levels 2 h after angiography were positively related
      with Cys C at 12 and 24 h and Scr at 48 h after angiography ( r = 0.34, r = 0.51,
      r = 0.85, p < 0.05, respectively). Conclusions Our results showed that variations
      in urinary Fg levels are consistent with serum Cys C and Scr in patients
      undergoing angiography and that urinary Fg levels were the earliest parameter to
      become elevated. Urinary Fg should be investigated as a useful predictor for
      abnormal renal function after angiography.

PMID- 30200829
TI  - N-Acylhomoserine lactone-mediated quorum sensing regulates biofilm structure in
      Methylobacterium populi P-1M, an isolate from a pink-pigmented household biofilm.
AB  - : Numerous gram-negative bacteria have quorum-sensing systems and produce AHL as
      a quorum-sensing signal molecule. In this study, we demonstrated that
      Methylobacterium populi P-1M, an isolate from a pink-pigmented household biofilm,
      produced two AHLs, C14:1-HSL as a predominant product and 3OHC14-HSL as a minor
      product. The complete genome sequence of M. populi P-1M revealed the presence of
      genes that are predicted to encode an AHL synthase (mpoI) and AHL receptor
      (mpoR). M. populi P-1M formed a pellicle-like biofilm, which had a flat surface
      and was easily removable. In contrast, biofilms formed by mpoI and/or mpoR
      deletion mutants had a wavy surface structure and strongly adhered to the glass
      tube. When C14:1-HSL was added to the mpoI mutant culture, the biofilm structure
      resembled that of the wild-type strain. These results demonstrated that the
      structure and adhesion strength of M. populi P-1M biofilms are determined in part
      by AHL-mediated quorum sensing. ABBREVIATIONS: AHL: N-acyl-l-homoserine lactone;
      C14:1-HSL: N-tetradecenoyl-l-homoserine lactone; 3OHC14-HSL: N-(3
      hydroxytetradecanoyl)-l-homoserine lactone; SAM: S-adenosyl-l-methionine; ACP:
      acyl-acyl carrier protein; EPS: extracellular polysaccharide; DMSO: dimethyl
      sulfoxide.

PMID- 30200832
TI  - Corrigendum.

PMID- 30200830
TI  - Systemic Necrotizing Vasculitis in Sheep Is Associated With Ovine Herpesvirus 2.
AB  - Ovine herpesvirus 2 (OvHV-2) is one of the gammaherpesviruses in the genus
      Macavirus that can cause malignant catarrhal fever (MCF) in ungulates. Sheep are
      the adapted host for OvHV-2 and it is generally assumed that infection is not
      associated with disease in this species. However, cases of "polyarteritis nodosa"
      or idiopathic systemic necrotizing vasculitis reported in sheep are similar to
      vascular lesions in clinically susceptible species with MCF. Using a recently
      developed in situ hybridization (ISH) method, we were able to identify OvHV-2
      nucleic acids within lesions and correlate the viral distribution with systemic
      necrotizing vasculitis in 9 sheep, including both naturally and experimentally
      OvHV-2-infected animals. ISH, combined with polymerase chain reaction and
      histology, identify OvHV-2 as the likely agent responsible for sporadic, MCF-like
      vascular disease in sheep.

PMID- 30200833
TI  - Novel alpha-Globin Splice Site Mutation (HBA2: c.96-5C>A) in Combination with
      Three-Gene Deletion Hb H Disease.
AB  - The choice of acceptor splice site during exon-exon splicing by the spliceosome
      is determined by a variety of factors. We report here a family with a novel
      acceptor splice site variant within intron 1 of the alpha-globin gene that
      provides some in vivo insight into the rules governing RNA splicing in homo
      sapiens. A 2-year-old female with Hb H disease, was found to have not only three
      alpha-globin genes deleted (- -FIL/-alpha3.7) but also a HBA2: c.96-5C>A variant
      on her remaining alpha-globin gene. The HBA2: c.96-5C>A variant was in cis with 
      alpha3.7 and mRNA studies indicate that this variant creates a new acceptor
      splice site which is used in approximately 35.0% of alpha-globin mRNA
      transcripts. The reduced levels of normal mRNA transcript predicts a more severe
      Hb H disease than expected for the three-gene deletion Hb H disease with a
      phenotype similar to nondeletional Hb H disease. We propose that this variant be
      called Hb Beach Haven (HBA2: c.96-5C>A).

PMID- 30200834
TI  - Assessment of Peripheral Neuropathy in Patients with beta-Thalassemia via
      Electrophysiological Study: Reevaluation in the Era of Iron Chelators.
AB  - Peripheral neuropathy is one of the complications of beta-thalassemia (beta-thal)
      that has been investigated in limited reports. We aimed to detect the rate of
      peripheral neuropathy and risk factors for neuropathy development in patients
      with beta-thal. The study was performed in patients with beta-thal intermedia
      (beta-TI) or beta-thal major (beta-TM). Prospective electrophysiological studies
      were achieved via standard procedures. A total of 27 patients were enrolled in
      the study. Electrophysiological studies for both motor and sensory nerves were
      within normal range. In motor nerve studies, delayed peroneal nerve latency was
      found in patients with high ferritin levels, increased ulnar nerve amplitude was
      detected in patients >=20 years old, and increased tibial nerve amplitude was
      seen in patients with low copper levels. We could not show peripheral neuropathy
      in our patients. Increased ferritin level, older age, and copper deficiency may
      cause mild changes in electrophysiological studies of motor nerves.

PMID- 30200835
TI  - Study on the Role of Polymorphisms of the SOX-6 and MYB Genes and Fetal
      Hemoglobin Levels in Sicilian Patients with beta-Thalassemia and Sickle Cell
      Disease.
AB  - The hemoglobinopathies, as beta-thalassemia (beta-thal) and sickle cell disease,
      are the most common hereditary hemolytic anemias. The increase of fetal
      hemoglobin (Hb F) levels can ameliorate the symptoms of hemoglobinopathies. There
      are several transcription factors such as MYB and SOX-6, which are involved in
      the regulation of Hb F. There are not enough studies investigating the
      association between single nucleotide polymorphisms (SNPs) of the SOX-6 and MYB
      genes and the variation of Hb F levels in patients affected by sickle cell
      disease and beta-thal. We therefore decided to analyze the role of four missense
      variants of MYB and SOX-6 genes in the regulation of Hb F levels. In order to do
      so, we examinated 30 Sicilian patients affected by sickle cell disease and beta
      thal, to understand if these variants could also have an influence in our
      populations. Comparing two groups of patients with low and high levels of Hb F,
      we found no significant differences in the genetic distribution and allelic
      frequency of MYB and SOX-6 gene polymorphisms. We also created and compared a
      'high producer' and 'low producer' genotype with different genes achieving the
      same result of no significant difference. Our results may be due either to the
      fact that the association between these genes and the regulation of Hb F levels
      are influenced by environmental history and population genetics, or to the small
      number of samples being analyzed.

PMID- 30200836
TI  - Factor V Leiden G1691A, Prothrombin G20210A, and MTHFR C677T and A1298C Mutations
      in Patients With Sickle Cell Disease in Tunisia.
AB  - Sickle cell disease is a genetic disorder characterized by a hypercoagulable
      state. Several complications in this hemoglobinopathy are increased by
      thrombosis. Factor V Leiden (FVL), prothrombin (PRT) G20210A, and
      methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C mutations are major
      inherited risk factors of thrombotic complications. In this study, our aim was to
      compare the frequencies of these mutations in sickle cell patients with healthy
      controls. The study population comprised 35 homozygous Hb S (HBB: c.20A>T)
      patients, 29 compound heterozygous patients [16 Hb S/beta0-thalassemia (beta0
      thal), four Hb S/beta+-thal, seven Hb S/Hb C (HBB: c.19G>A) and two Hb S/Hb O
      Arab (HBB: c.364G>A)] and 100 healthy subjects. All patients and controls were
      subjected to laboratory investigations as well as mutation genotyping. Our
      findings showed a severe anemia with the lowest values of protein S (PS), protein
      C (PC) and antithrombin (AT) in the homozygous Hb S group compared to Hb S/Hb C
      and Hb S/beta-thal subjects. No significant difference in FVL genotype between
      patients and controls was observed, whereas high frequencies of PRT G20210A,
      MTHFR C677T and MTHFR A1298C mutations in the Hb S patients and a significant
      association between the MTHFR C677T mutation and Hb S/beta0-thal were found.

PMID- 30200837
TI  - Molecular Characterization of beta-Thalassemia Mutations Via the Amplification
      Refractory Mutation System-Polymerase Chain Reaction Method at the North
      Waziristan Agency, Pakistan.
AB  - beta-Thalassemia (beta-thal) is a monogenic disease characterized by mutations on
      the HBB gene, affecting the production of globin that results in hypochromic and
      microcytic anemia. The aim of this study was to determine the prevalence of six
      common beta-thal mutations, and their frequency and inheritance pattern in
      affected populations of North Waziristan Agency, Pakistan. In this study, 130
      blood samples from 37 unrelated beta-thalassemic families having a minimum of one
      transfusion-dependent child with beta-thal major (beta-TM), were retrieved either
      from the Thalassaemia Centre for Women and Children Hospital Bannu or their home
      towns situated in Noth Waziristan Agency. All samples were analyzed by the
      amplification refractory mutation system-polymerase chain reaction (ARMS-PCR)
      using six allele-specific primers for the presence of the six beta-thal mutations
      common in the Pakistani population. Of the six common mutations, our study
      demonstrated five HBB mutations comprising HBB: c.27_28insG, HBB: c.92+5G>C, HBB:
      c.126_129delCTTT, HBB: c.92+1G>T and HBB: c.17_18delCT from the families studied,
      while mutation HBB: c.47G>A [codon 15 (G>A)] was not detected in any of the
      studied families. Furthermore, the HBB: c.27_28insG and HBB: c.92+5G>C were noted
      to be the most common with frequencies of 42.85 and 31.42%, respectively. The
      findings of the present study may be useful in launching carrier screening and
      prenatal diagnosis (PND) programs by screening analyzed and other unanalyzed
      affected families for the possible presence of common mutations through the ARMS
      PCR technique that will help to control the disease.

PMID- 30200838
TI  - Compound Heterozygosity of beta-Thalassemia and the Sickle Cell Hemoglobin in
      Various Populations of Chhattisgarh State, India.
AB  - Hemoglobinopathies evolved as a protective mechanism against malaria, which
      exhibit selective advantage in the heterozygous state. However, in a homozygous
      recessive condition, it poses a serious socioeconomic burden. Sickle cell anemia
      is an autosomal recessive hemoglobinopathy associated with erythrocytes sickling,
      vaso-occlusive crisis (VOC), as well as multi-organ failure and death. The
      coinheritance of other hemoglobinopathies is known to substantially modulate the
      clinical manifestation of sickle cell anemia. In the present study, we aimed to
      analyze the coinheritance of beta-thalassemia (beta-thal) in Hb S (HBB: c.20A>T)
      patients. The study includes 918 sickle cell anemia patients from 10 ethnic
      populations of Chhattisgarh State, India. Complete blood counts (CBCs) and
      hemoglobin (Hb) high performance liquid chromatography (HPLC) fractionation data
      were collected from patient record books. We observed Hb S-beta-thal in all the
      analyzed populations. Interestingly, high frequencies of Hb S-beta-thal have been
      observed in Satnami (53.8%), Rawat (47.1%), Gond (35.1%) and Panika (30.6%)
      populations. Inter-population comparison of hematological parameters [Hb F (p <
      0.001), Hb A2 (p < 0.001), Hb (p = 0.03) and red blood cell distribution width
      (RDW) (p < 0.001)] revealed significant differences. We also observed that mean
      Hb F levels were significantly higher in Hb S compared to Hb S-beta-thal patients
      in the respective populations. Our study highlights the higher prevalence of beta
      thal as well as the compound heterozygosity for Hb S and beta-thal in various
      populations of Chhattisgarh State, India.

PMID- 30200839
TI  - Pilot study using intraoperative fluorescence angiography during arteriovenous
      hemodialysis access surgery.
AB  - INTRODUCTION: In this pilot study, we used indocyanine green fluorescence
      angiography during hemodialysis access surgery. The aim was to evaluate its
      relevance as a diagnostic tool to visualize changes in hand microperfusion.
      PATIENTS AND METHODS: In this prospective single-center study, 47 adult patients
      (33 male, 14 female) with renal disease (24 preemptive, 23 endstage) were
      enrolled. Surgical creation of an arteriovenous fistula was performed (22
      forearm, 25 upper arm). Microperfusion of the ipsilateral hand and fingers was
      evaluated intraoperatively using indocyanine green fluorescence angiography. We
      compared the cumulated microperfusion parameters ingress (In) and ingress rate
      (InR) before and after opening of the anastomosis. To compare the dimension of
      microcirculatory decline, we calculated the ratios of the parameters (RatioIn and
      RatioInR) after to those before anastomosis opening. RESULTS: The cumulated
      microperfusion parameters In and InR showed a significant decrease after
      completion of anastomosis and declamping. This effect has been seen in all
      patients for the hand and for each finger consecutively. During follow-up (mean
      4.6, range 3-11 months), 5 patients (10.6%) complained about hemodialysis access
      induced distal ischemia. The ratio of intraoperative microperfusion in those five
      hemodialysis access-induced ischemia patients was significantly lower compared to
      asymptomatic patients (RatioIn 0.23 vs 0.58, p = 0.001, and RatioInR 0.25 vs
      0.62, p = 0.003). CONCLUSION: Intraoperative fluorescence angiography could
      visualize the deterioration of ipsilateral hand microperfusion after surgical
      creation of an arteriovenous fistula. It seems to be a promising tool to detect
      patients at risk for hemodialysis access-induced distal ischemia early in the
      peri- or even intraoperative stage.

PMID- 30200842
TI  - Appropriateness of granulocyte colony-stimulating factor use in patients
      receiving chemotherapy by febrile neutropenia risk level.
AB  - Objective Inappropriate granulocyte colony-stimulating factor use with
      myelosuppressive chemotherapy has been reported. Using the Oncology Services
      Comprehensive Electronic Records electronic medical record database, prophylactic
      granulocyte colony-stimulating factor (pegfilgrastim/filgrastim) use in cancer
      patients was assessed by febrile neutropenia risk level. Methods Patients with
      nonmetastatic or metastatic breast, head/neck, colorectal, ovarian/gynecologic,
      lung cancer, or non-Hodgkin's lymphoma who received myelosuppressive chemotherapy
      from June 2013 to May 2014 were included. Prophylactic granulocyte colony
      stimulating factor use with high-risk, intermediate-risk, and low-risk
      chemotherapy and distribution of National Comprehensive Cancer Network risk
      factors with intermediate-risk regimens were assessed. Results Overall, 86,189
      patients received ~4.2 million chemotherapy cycles (high risk, 9%; intermediate
      risk, 48%; low risk, 43%). Prophylactic granulocyte colony-stimulating factor was
      given in 24% of cycles (high risk, 59%; intermediate risk, 29%; low risk, 11%).
      For nonmetastatic solid tumors, granulocyte colony-stimulating factor was given
      in 78% (high risk), 31% (intermediate risk), and 6% (low risk) of cycles. For
      metastatic solid tumors or non-Hodgkin's lymphoma, granulocyte colony-stimulating
      factor was given in 50% (high risk), 27% (intermediate risk), and 11% (low risk)
      of cycles. Among patients receiving intermediate-risk regimens with granulocyte
      colony-stimulating factor, febrile neutropenia risk factors were identified in
      56% (95% confidence interval, 51.1-60.9%) of patients with nonmetastatic solid
      tumors (n = 400) and in 70% (64.5-73.5%) of patients with metastatic solid tumors
      or non-Hodgkin's lymphoma (n = 400). Conclusion Prophylactic granulocyte colony
      stimulating factor use was appropriately highest for high-risk regimens and
      lowest for low-risk regimens yet still potentially underused in high risk
      regimens, overused in low-risk regimens, and not appropriately targeted in
      intermediate-risk regimens, indicating a need for further education on febrile
      neutropenia risk evaluation and appropriate granulocyte colony-stimulating factor
      use.

PMID- 30200843
TI  - Developing recommendations for the safe handling of oral anti-cancer drugs in
      community pharmacies: A pan-Canadian consensus approach.
AB  - Purpose To create a set of consensus-based and evidence-informed recommendations
      to provide guidance around the safe dispensing and handling of oral anti-cancer
      drugs in low-volume settings unique to the community pharmacy setting. Methods A
      review of published and grey literature (published in non-commercial domains such
      as national organizations and associations) documents and nine key informant
      interviews were conducted and a modified Delphi approach was taken to achieve
      consensus. The final list of 47 candidate recommendations was reviewed by a task
      force and validated by multi-disciplinary stakeholders. A draft of the statements
      was circulated broadly within the community pharmacy community in an effort to
      assess relevance and implementation feasibility. Results The final report
      included 44 recommendations that addressed 11 key areas germane to the safe
      handling of oral anti-cancer drugs in community pharmacies. Mean agreement
      increased from 70% to 95%. Early feedback from community pharmacy leaders during
      the external review suggests that many of the proposed recommendations can be
      feasibly implemented within a reasonable timeframe when released with appropriate
      education and resource materials. Conclusions A modified-Delphi approach
      supplemented by key informant interviews and a comprehensive external review
      resulted in a set of evidence-informed, community-driven recommendations for
      community pharmacies. The recommendations address a gap in existing literature to
      improve understanding of the risks associated with handling and dispensing oral
      anti-cancer drugs for both community pharmacy staff and management and offer
      mitigating strategies to reduce those risks. Incorporating feasibility assessment
      actions early (through the key informant interviews) and late (through the
      external review) ensures recommendations are grounded in practicality and support
      broad and early knowledge translation strategies.

PMID- 30200844
TI  - Preservation of cognitive function following whole brain radiotherapy in patients
      with brain metastases: Complications, treatments, and the emerging role of
      memantine.
AB  - Whole brain radiotherapy is the mainstay of treatment for patients suffering from
      stage IV malignancies that have metastasized to the brain. Although this therapy
      is often effective at reducing tumor size and burden, it is associated with a
      spectrum of toxicities that often result in irreversible cognitive decline.
      Various drug and non-drug therapies have been evaluated to treat this
      neurotoxicity after whole brain radiotherapy is administered; however, currently
      available options have shown little benefit or come with side effects themselves
      that may outweigh the benefits of their use. For this reason, current
      investigations are focusing on preventing cognitive decline, rather than
      attempting to attenuate symptoms after they occur. Memantine has consistently
      shown promise in both in-vitro and in-vivo studies as a neuroprotective agent
      that may improve cognitive outcomes in patients undergoing whole brain
      radiotherapy. Memantine use prior to and during whole brain radiotherapy has been
      shown to significantly delay time to cognitive failure and reduce the rate of
      decline in memory, cognitive function, and processing speed. Its use has also
      been linked to significant decreases in brain edema, brain infarct size, and
      brain vasculature changes following whole brain radiotherapy. Memantine offers a
      promising safety profile with high tolerability and limited side effects. The
      objective of this article is to provide an overview of the target patient
      population, the neurotoxic effects of WBRT, current treatment options, and a
      summary of the available literature surrounding the use of memantine in this
      setting.

PMID- 30200840
TI  - Characterization of cis-acting elements that control oscillating alternative
      splicing.
AB  - Alternative splicing (AS) in response to changing external conditions often
      requires alterations in the ability of sequence-specific RNA-binding proteins to
      bind to cis-acting sequences in their target pre-mRNA. While daily oscillations
      in AS events have been described in several organisms, cis-acting sequences that
      control time of the day-dependent AS remain largely elusive. Here we define cis
      regulatory RNA elements that control body-temperature driven rhythmic AS using
      the mouse U2af26 gene as a model system. We identify a complex network of cis
      regulatory sequences that regulate AS of U2af26, and show that the activity of
      two enhancer elements is necessary for oscillating AS. A minigene comprising
      these U2af26 regions recapitulates rhythmic splicing of the endogenous gene,
      which is controlled through temperature-regulated SR protein phosphorylation.
      Mutagenesis of the minigene delineates the cis-acting enhancer element for SRSF2
      within exon 6 to single nucleotide resolution and reveals that the combined
      activity of SRSF2 and SRSF7 is required for oscillating U2af26 AS. By combining
      RNA-Seq with an siRNA screen and individual-nucleotide resolution cross-linking
      and immunoprecipitation (iCLIP), we identify a complex network of SR proteins
      that globally controls temperature-dependent rhythmic AS, with the direction of
      splicing depending on the position of the cis-acting elements. Together, we
      provide detailed insights into the sequence requirements that allow trans-acting
      factors to generate daily rhythms in AS.

PMID- 30200847
TI  - Introduction.

PMID- 30200845
TI  - Thromboembolic disease in females and males aged 10 to 39 years in Germany.
AB  - BACKGROUND: We analysed differences in hospitalization rates for venous diseases
      such as pulmonary embolism (PE), deep vein thrombosis (DVT), sinus vein
      thrombosis (SVT), portal vein thrombosis (PVT), and Budd-Chiari syndrome (BCS) as
      well as for arterial diseases such as myocardial infarction (MI) and embolic
      stroke (ES) in females and males aged 10 to 39 years. PATIENTS AND METHODS:
      Detailed lists of hospitalizations with the principal and additional diagnoses
      for PE (ICD-code I26.0 + I26.9), DVT (I80.0-I80.9), SVT (I67.6), PVT (I81), BCS
      (I82.0), MI (I21.0-I21.9), and ES (I63.1 + I63.4) in males and females aged 10 to
      39 years in the years 2006 to 2015 were provided by the Federal Statistical
      Office in Germany. RESULTS: Considering the 10-year period there were more female
      than male cases hospitalized with the principal diagnoses for PE, DVT, SVT, and
      BCS. Looking at the principal diagnosis of the year 2015, one can see a steep
      increase in numbers of hospitalization for PE, DVT, and SVT in females ranging
      from the ages 12 to 13 and 14 to 15 years compared to males. The curves of PE and
      DVT meet again in the age group between 32 and 33 years, but not for SVT. The
      greatest differences are seen at the end of the second and at the beginning of
      the third decade of life. In contrast, MI was more frequent in young males
      beginning at the age of 18 to 19 years. The number of female and male cases with
      ES and PVT were almost similar in the different age groups. CONCLUSIONS: The
      presented data show higher hospitalization rates for females in the age group 10
      to 39 years for different venous thrombosis but not for MI and ES.

PMID- 30200848
TI  - Broadening the Definition of Bacterial Small RNAs: Characteristics and Mechanisms
      of Action.
AB  - The first report of trans-acting RNA-based regulation in bacterial cells dates
      back to 1984. Subsequent studies in diverse bacteria unraveled shared properties
      of trans-acting small regulatory RNAs, forming a clear definition of these
      molecules. These shared characteristics have been used extensively to identify
      new small RNAs (sRNAs) and their interactomes. Recently however, emerging
      technologies able to resolve RNA-RNA interactions have identified new types of
      regulatory RNAs. In this review, we present a broader definition of trans-acting
      sRNA regulators and discuss their newly discovered intrinsic characteristics.

PMID- 30200849
TI  - Pneumococcal Vaccines: Host Interactions, Population Dynamics, and Design
      Principles.
AB  - Streptococcus pneumoniae (the pneumococcus) is a nasopharyngeal commensal and
      respiratory pathogen. Most isolates express a capsule, the species-wide diversity
      of which has been immunologically classified into ~100 serotypes. Capsule
      polysaccharides have been combined into multivalent vaccines widely used in
      adults, but the T cell independence of the antibody response means they are not
      protective in infants. Polysaccharide conjugate vaccines (PCVs) trigger a T cell
      dependent response through attaching a carrier protein to capsular
      polysaccharides. The immune response stimulated by PCVs in infants inhibits
      carriage of vaccine serotypes (VTs), resulting in population-wide herd immunity.
      These were replaced in carriage by non-VTs. Nevertheless, PCVs drove reductions
      in infant pneumococcal disease, due to the lower mean invasiveness of the
      postvaccination bacterial population; age-varying serotype invasiveness resulted
      in a smaller reduction in adult disease. Alternative vaccines being tested in
      trials are designed to provide species-wide protection through stimulating innate
      and cellular immune responses, alongside antibodies to conserved antigens.

PMID- 30200850
TI  - Antibiotic-Induced Genetic Variation: How It Arises and How It Can Be Prevented.
AB  - By targeting essential cellular processes, antibiotics provoke metabolic
      perturbations and induce stress responses and genetic variation in bacteria. Here
      we review current knowledge of the mechanisms by which these molecules generate
      genetic instability. They include production of reactive oxygen species, as well
      as induction of the stress response regulons, which lead to enhancement of
      mutation and recombination rates and modulation of horizontal gene transfer. All
      these phenomena influence the evolution and spread of antibiotic resistance. The
      use of strategies to stop or decrease the generation of resistant variants is
      also discussed.

PMID- 30200851
TI  - Ebola: Lessons on Vaccine Development.
AB  - The West African Ebola virus (EBOV) epidemic has fast-tracked countermeasures for
      this rare, emerging zoonotic pathogen. Until 2013-2014, most EBOV vaccine
      candidates were stalled between the preclinical and clinical milestones on the
      path to licensure, because of funding problems, lack of interest from
      pharmaceutical companies, and competing priorities in public health. The
      unprecedented and devastating epidemic propelled vaccine candidates toward
      clinical trials that were initiated near the end of the active response to the
      outbreak. Those trials did not have a major impact on the epidemic but provided
      invaluable data on vaccine safety, immunogenicity, and, to a limited degree, even
      efficacy in humans. There are plenty of lessons to learn from these trials, some
      of which are addressed in this review. Better preparation is essential to
      executing an effective response to EBOV in the future; yet, the first indications
      of waning interest are already noticeable.

PMID- 30200852
TI  - The Glyoxylate Shunt, 60 Years On.
AB  - 2017 marks the 60th anniversary of Krebs' seminal paper on the glyoxylate shunt
      (and coincidentally, also the 80th anniversary of his discovery of the citric
      acid cycle). Sixty years on, we have witnessed substantial developments in our
      understanding of how flux is partitioned between the glyoxylate shunt and the
      oxidative decarboxylation steps of the citric acid cycle. The last decade has
      shown us that the beautifully elegant textbook mechanism that regulates carbon
      flux through the shunt in E. coli is an oversimplification of the situation in
      many other bacteria. The aim of this review is to assess how this new knowledge
      is impacting our understanding of flux control at the TCA cycle/glyoxylate shunt
      branch point in a wider range of genera, and to summarize recent findings
      implicating a role for the glyoxylate shunt in cellular functions other than
      metabolism.

PMID- 30200853
TI  - The Outer Membrane Took Center Stage.
AB  - My interest in membranes was piqued during a lecture series given by one of the
      founders of molecular biology, Max Delbruck, at Caltech, where I spent a
      postdoctoral year to learn more about protein chemistry. That general interest
      was further refined to my ultimate research focal point-the outer membrane of
      Escherichia coli-through the influence of the work of Wolfhard Weidel, who
      discovered the murein (peptidoglycan) layer and biochemically characterized the
      first phage receptors of this bacterium. The discovery of lipoprotein bound to
      murein was completely unexpected and demonstrated that the protein composition of
      the outer membrane and the structure and function of proteins could be unraveled
      at a time when nothing was known about outer membrane proteins. The research of
      my laboratory over the years covered energy-dependent import of proteinaceous
      toxins and iron chelates across the outer membrane, which does not contain an
      energy source, and gene regulation by iron, including transmembrane
      transcriptional regulation.

PMID- 30200854
TI  - Detection of Microbial Infections Through Innate Immune Sensing of Nucleic Acids.
AB  - Microbial infections are recognized by the innate immune system through germline
      encoded pattern recognition receptors (PRRs). As most microbial pathogens contain
      DNA and/or RNA during their life cycle, nucleic acid sensing has evolved as an
      essential strategy for host innate immune defense. Pathogen-derived nucleic acids
      with distinct features are recognized by specific host PRRs localized in
      endolysosomes and the cytosol. Activation of these PRRs triggers signaling
      cascades that culminate in the production of type I interferons and
      proinflammatory cytokines, leading to induction of an antimicrobial state,
      activation of adaptive immunity, and eventual clearance of the infection. Here,
      we review recent progress in innate immune recognition of nucleic acids upon
      microbial infection, including pathways involving endosomal Toll-like receptors,
      cytosolic RNA sensors, and cytosolic DNA sensors. We also discuss the mechanisms
      by which infectious microbes counteract host nucleic acid sensing to evade immune
      surveillance.

PMID- 30200855
TI  - A New Lens for RNA Localization: Liquid-Liquid Phase Separation.
AB  - RNA localization mechanisms have been intensively studied and include localized
      protection of mRNA from degradation, diffusion-coupled local entrapment of mRNA,
      and directed transport of mRNAs along the cytoskeleton. While it is well
      understood how cells utilize these three mechanisms to organize mRNAs within the
      cytoplasm, a newly appreciated mechanism of RNA localization has emerged in
      recent years in which mRNAs phase-separate and form liquid-like droplets. mRNAs
      both contribute to condensation of proteins into liquid-like structures and are
      themselves regulated by being incorporated into membraneless organelles. This
      ability to condense into droplets is in many instances contributing to previously
      appreciated mRNA localization phenomena. Here we review how phase separation
      enables mRNAs to selectively and efficiently colocalize and be coregulated,
      allowing control of gene expression in time and space.

PMID- 30200856
TI  - The Promise of a Malaria Vaccine-Are We Closer?
AB  - Malaria vaccine development has rapidly advanced in the past decade. The very
      first phase 3 clinical trial of the RTS,S vaccine was completed with over 15,000
      African infants and children, and pilot implementation studies are underway. Next
      generation candidate vaccines using novel antigens, platforms, or approaches
      targeting different and/or multiple stages of the Plasmodium life cycle are being
      tested. Many candidates, in various stages of development, promise enhanced
      efficacy of long duration and broad protection against genetically diverse
      malaria strains, with a few studies under way in target populations in endemic
      areas. Malaria vaccines together with other interventions promise interruption
      and eventual elimination of malaria in endemic areas.

PMID- 30200857
TI  - Transcriptional Responses to ppGpp and DksA.
AB  - The stringent response to nutrient deprivation is a stress response found
      throughout the bacterial domain of life. Although first described in
      proteobacteria for matching ribosome synthesis to the cell's translation status
      and for preventing formation of defective ribosomal particles, the response is
      actually much broader, regulating many hundreds of genes-some positively, some
      negatively. Utilization of the signaling molecules ppGpp and pppGpp for this
      purpose is ubiquitous in bacterial evolution, although the mechanisms employed
      vary. In proteobacteria, the signaling molecules typically bind to two sites on
      RNA polymerase, one at the interface of the beta' and omega subunits and one at
      the interface of the beta' secondary channel and the transcription factor DksA.
      The beta' secondary channel is targeted by other transcription regulators as
      well. Although studies on the transcriptional outputs of the stringent response
      date back at least 50 years, the mechanisms responsible are only now coming into
      focus.

PMID- 30200858
TI  - Role of astaxanthin in the modulation of brain-derived neurotrophic factor and
      spatial learning behavior in perinatally undernourished Wistar rats.
AB  - OBJECTIVE: Maternal health and nutrition during the perinatal period is the
      predominant factor influencing the functional development of the brain. Maternal
      malnutrition during the perinatal period causes retardation of brain development.
      The current study investigates the role of Astaxanthin (AsX) in spatial learning
      and memory and BDNF in perinatally undernourished Wistar rats. METHODS: The
      albino wistar rats were perinatally undernourished and administered with
      different dosages of AsX. The spatial learning and memory performance and BDNF
      level were assessed. Data were collected and analysed. RESULTS: The % Correct
      choice during the acquisition phase, performance at the end of the acquisition
      phase and the mean BDNF level at the Hippocampus, Cerebellum, and Cerebral cortex
      showed significant decline (P<0.001) in the PUN group and significantly high
      (P<0.001) in the PUNA2 group compared to the control. However, the mean RME and
      mean WME during different days of the acquisition phase were significantly high
      (P<0.001) in the PUN group and insignificant (P>0.05) in PUNA2 compared to the
      control. DISCUSSION: The results showed that AsX effectively modulated the
      cognitive deficit that occurred in perinatally undernourished rats. This can be
      attributed to BDNF upregulation as evidenced by the significant increase of the
      BDNF level.

PMID- 30200859
TI  - A concise synthesis of peramine, a metabolite of endophytic fungi.
AB  - The total synthesis of peramine, a natural product isolated from an endophytic
      fungi, has been achieved in four steps and 34% overall yield from known
      compounds. The key step was the one-pot construction of the pyrrolopyrazinone
      ring from pyrrole amide and propargyl bromide. The preparation of peramine-d4 as
      an internal standard for quantitative analysis by MS is also described.

PMID- 30200861
TI  - Many moral buttons or just one? Evidence from emotional facial expressions.
AB  - We investigated whether moral violations involving harm selectively elicit anger,
      whereas purity violations selectively elicit disgust, as predicted by the Moral
      Foundations Theory (MFT). We analysed participants' spontaneous facial
      expressions as they listened to scenarios depicting moral violations of harm and
      purity. As predicted by MFT, anger reactions were elicited more frequently by
      harmful than by impure actions. However, violations of purity elicited more
      smiling reactions and expressions of anger than of disgust. This effect was found
      both in a classic set of scenarios and in a new set in which the different kinds
      of violations were matched on weirdness. Overall, these findings are at odds with
      predictions derived from MFT and provide support for "monist" accounts that posit
      harm at the basis of all moral violations. However, we found that smiles were
      differentially linked to purity violations, which leaves open the possibility of
      distinct moral modules.

PMID- 30200862
TI  - Recent Advances in the Studies of Molecular Mechanisms Regulating Multidrug
      Resistance in Cancer Cells.
AB  - Here we present new approaches to better understanding multidrug resistance (MDR)
      development in cancer cells, such as identification of components of a complex
      process of MDR evolution. Recent advances in the studies of MDR are discussed: 1)
      chemotherapy agents might be involved in the selection of cancer stem cells
      resulting in the elevated drug resistance and enhanced tumorigenicity; 2) cell
      cell interactions have a great effect on the MDR emergence and evolution; 3)
      mechanotransduction is an important signaling mechanism in cell-cell
      interactions; 4) proteins of the ABC transporter family which are often involved
      in MDR might be transferred between cells via microvesicles (epigenetic MDR
      regulation); 5) proteins providing cell-to-cell transfer of functional P
      glycoprotein (MDR1 protein) via microvesicles have been investigated; 6) P
      glycoprotein may serve to regulate apoptosis, as well as transcription and
      translation of target genes/proteins. Although proving once again that MDR is a
      complex multi-faceted process, these data open new approaches to overcoming it.

PMID- 30200863
TI  - Signaling Mechanisms Regulating Diverse Plant Cell Responses to UVB Radiation.
AB  - UVB radiation (290-320 nm) causes diverse effects in plant cells that vary with
      the fluence rate of exposure. High fluence rates of UVB radiation cause damage to
      DNA and formation of reactive oxygen species in mitochondria and chloroplasts,
      which lead to oxidation of membrane proteins and lipids and inhibition of
      cellular functions. In response to oxidative stress, mitochondrial transmembrane
      potential dissipates, resulting in cytochrome c release and activation of
      metacaspases. This leads to the apoptosis-like cell death. The signaling
      mechanism based on UVB DNA damage includes checkpoint activation, cell-cycle
      arrest, and finally programmed cell death with characteristic DNA fragmentation
      and morphological hallmarks typical of apoptotic cells. Recently, it was shown
      that among the components of this signaling mechanism the transcriptional factor
      SOG1 (suppressor of gamma response 1) plays a key role in regulation of
      programmed cell death in plants. In contrast to its damaging effects, UVB
      radiation at low fluence rates can act as a regulatory signal that is
      specifically perceived by plants to promote acclimation and survival in sunlight.
      The protective action of UVB is based on expression of various genes, including
      those encoding flavonoid synthesis enzymes that provide a UVB-absorbing sunscreen
      in epidermal tissues and DNA photorepair enzymes. These processes are mediated by
      the UVB photoreceptor UVR8, which has been recently characterized at the
      molecular level. Now progress is made in uncovering the UVR8-mediated signaling
      pathway mechanism in the context of UVB photon perception and revealing the
      biochemical components of the early stages of light signal transduction. In this
      review, attention is focused on the achievements in studying these UVB-induced
      signaling processes.

PMID- 30200864
TI  - Why Threonine Is an Essential Amino Acid in Mammals and Birds: Studies at the
      Enzyme Level.
AB  - The only pathway for the synthesis of essential amino acids in vertebrates is
      reversible transamination of their keto analogs with glutamic acid. At the same
      time, it is commonly accepted that such essential amino acids as lysine and
      threonine are not involved in transamination and, therefore, cannot be
      synthesized from their keto analogs. However, using radiolabeled isotopes,
      synthesis of threonine was demonstrated in rat liver and in a reaction mixture
      containing chicken liver threonine dehydrogenase. In the review, we discuss why
      threonine is an essential amino acid in mammals and birds based on the pathways
      of threonine biosynthesis in these two classes of vertebrates.

PMID- 30200865
TI  - The Regulatory Role of NAD in Human and Animal Cells.
AB  - Nicotinamide adenine dinucleotide (NAD) and its phosphorylated form NADP are the
      major coenzymes in the redox reactions of various essential metabolic pathways.
      NAD+ also serves as a substrate for several families of regulatory proteins, such
      as protein deacetylases (sirtuins), ADP-ribosyltransferases, and poly(ADP-ribose)
      polymerases, that control vital cell processes including gene expression, DNA
      repair, apoptosis, mitochondrial biogenesis, unfolded protein response, and many
      others. NAD+ is also a precursor for calcium-mobilizing secondary messengers.
      Proper regulation of these NAD-dependent metabolic and signaling pathways depends
      on how efficiently cells can maintain their NAD levels. Generally, mammalian
      cells regulate their NAD supply through biosynthesis from the precursors
      delivered with the diet: nicotinamide and nicotinic acid (vitamin B3), as well as
      nicotinamide riboside and nicotinic acid riboside. Administration of NAD
      precursors has been demonstrated to restore NAD levels in tissues (i.e., to
      produce beneficial therapeutic effects) in preclinical models of various
      diseases, such as neurodegenerative disorders, obesity, diabetes, and metabolic
      syndrome.

PMID- 30200866
TI  - Involvement of Mitochondria in Neurodegeneration in Multiple Sclerosis.
AB  - Functional disruption and neuronal loss followed by progressive dysfunction of
      the nervous system underlies the pathogenesis of numerous disorders defined as
      "neurodegenerative diseases". Multiple sclerosis, a chronic inflammatory
      demyelinating disease of the central nervous system resulting in serious
      neurological dysfunctions and disability, is one of the most common
      neurodegenerative diseases. Recent studies suggest that disturbances in
      mitochondrial functioning are key factors leading to neurodegeneration. In this
      review, we consider data on mitochondrial dysfunctions in multiple sclerosis,
      which were obtained both with patients and with animal models. The contemporary
      data indicate that the axonal degeneration in multiple sclerosis largely results
      from the activation of Ca2+-dependent proteases and from misbalance of ion
      homeostasis caused by energy deficiency. The genetic studies analyzing
      association of mitochondrial DNA polymorphic variants in multiple sclerosis
      suggest the participation of mitochondrial genome variability in the development
      of this disease, although questions of the involvement of individual genomic
      variants are far from being resolved.

PMID- 30200867
TI  - Structure of the K82 Capsular Polysaccharide from Acinetobacter baumannii LUH5534
      Containing a d-Galactose 4,6-Pyruvic Acid Acetal.
AB  - Type K82 capsular polysaccharide (CPS) was isolated from Acinetobacter baumannii
      LUH5534. The structure of a linear tetrasaccharide repeating unit of the CPS was
      established by sugar analysis along with one- and two-dimensional 1H and 13C NMR
      spectroscopy. Proteins encoded by the KL82 capsule gene cluster in the genome of
      LUH5534 were assigned to roles in the synthesis of the K82 CPS. In particular,
      functions were assigned to two new glycosyltransferases (Gtr152 and Gtr153) and a
      novel pyruvyltransferase, Ptr5, responsible for the synthesis of d-galactose 4,6
      (R)-pyruvic acid acetal.

PMID- 30200868
TI  - Reproducible Peak Clusters on Differential Mouse Mortality Curves and Their
      Relation to the Gompertz Model.
AB  - It is shown that differentiation of mouse mortality curves (number of animals
      that died at a certain age plotted versus their lifespan) results in the
      appearance of eight clearly distinguished clusters of peaks corresponding to
      increased mortality rates. Smoothing of the original mortality curves and
      subsequent transformation of the differential mortality curves according to the
      Gompertz model makes the peaks and the corresponding clusters less pronounced and
      drives the logarithm of the force mortality curve toward a straight line. The
      positions of the clusters on the lifespan axis (expressed in days) were
      calculated as weighted means by dividing the sum of the products of
      multiplication of the peak heights and their position on the lifespan axis by the
      sum of the peak heights within a cluster. To prove that the peaks and their
      clusters are not random, we have demonstrated that the positions of the clusters
      on the lifespan axis do not depend on the extent of mortality curve smoothing or
      the group of mice analyzed.

PMID- 30200869
TI  - In vivo Proinflammatory Cytokine Production by CD-1 Mice in Response to
      Equipotential Doses of Rhodobacter capsulatus PG and Salmonella enterica
      Lipopolysaccharides.
AB  - The capacities of relatively nontoxic lipopolysaccharide (LPS) from Rhodobacter
      capsulatus PG and highly potent LPS from Salmonella enterica serovar Typhimurium
      to evoke proinflammatory cytokine production have been compared in vivo.
      Intravenous administration of S. enterica LPS at a relatively low dose (1 mg/kg
      body weight) led to upregulation of TNF-alpha, IL-6, and IFN-gamma production by
      non-sensitized CD-1 mice. LPS from R. capsulatus PG used at a four-times higher
      dose than that from S. enterica elicited production of almost the same amount of
      systemic TNF-alpha; therefore, the doses of 4 mg/kg LPS from R. capsulatus PG and
      1 mg/kg LPS from S. enterica were considered to be approximately equipotential
      doses with respect to the LPS-dependent TNF-alpha production by CD-1 mice.
      Rhodobacter capsulatus PG LPS was a weaker inducer of the production of TNF
      alpha, IL-6, and IFN-gamma, as compared to the equipotential dose of S. enterica
      LPS. Administration of R. capsulatus PG LPS before S. enterica LPS decreased
      production of IFN-gamma, but not of TNF-alpha and IL-6, induced by S. enterica
      LPS. Rhodobacter capsulatus PG LPS also suppressed IFN-gamma production induced
      by S. enterica LPS when R. capsulatus PG LPS had been injected as little as 10
      min after S. enterica LPS, but to a much lesser extent. Rhodobacter capsulatus PG
      LPS did not affect TNF-alpha and IL-6 production induced by the equipotential
      dose of S. enterica LPS. In order to draw conclusion on the endotoxic activity of
      particular LPSs, species-specific structure or arrangement of the animal or human
      immune systems should be considered.

PMID- 30200870
TI  - A Novel Fluorescent GFP Chromophore Analog-Based Dye for Quantitative PCR.
AB  - This is the first report describing the possibility of using a green fluorescent
      protein chromophore synthetic analog, P-HOBDI-BF2, as a fluorescent dye for a
      linear hydrolysis probe used in qPCR. The study was carried out on a system for
      detection of the plant pathogenic fungus Fusarium avenaceum using a plasmid
      containing translation elongation factor 1alpha fragment as a template. To
      estimate fluorogenic properties of P-HOBDI-BF2, 6-FAM- and BDP-FL-labeled probes
      were used. It was demonstrated that a synthetic dye based on the P-HOBDI-BF2
      chromophore can be used for labeling hydrolysis probes for qPCR, but fluorescence
      increase levels for P-HOBDI-BF2-labeled probes were slightly lower than those for
      6-FAM-labeled ones. At the same time, the sensitivity of P-HOBDI-BF2-based assays
      remained high, and this fact together with acceptable fluorescence levels
      suggests that this dye can be considered as an efficient alternative for
      reporters traditionally used for fluorescence detection in the FAM channel.

PMID- 30200871
TI  - Erratum to: "Rhamnose-Containing Cell Wall Glycopolymers from Rathayibacter
      toxicus VKM Ac-1600 and "Rathayibacter tanaceti" VKM Ac-2596" [Biochemistry
      (Moscow), 83, 717 (2018)].
AB  - This corrects the article DOI: 10.1134/S0006297918060093.

PMID- 30200872
TI  - The P450 gene CYP749A16 is required for tolerance to the sulfonylurea herbicide
      trifloxysulfuron sodium in cotton (Gossypium hirsutum L.).
AB  - BACKGROUND: Weed management is critical to global crop production and is
      complicated by rapidly evolving herbicide resistance in weeds. New sources of
      herbicide resistance are needed for crop plants so that applied herbicides can be
      rotated or combined to thwart the evolution of resistant weeds. The diverse
      family of cytochrome P450 proteins has been suggested to be a source of
      detoxifying herbicide metabolism in both weed and crop plants, and greater
      understanding of these genes will offer avenues for crop improvement and novel
      weed management practices. RESULTS: Here, we report the identification of
      CYP749A16 (Gh_D10G1401) which is responsible for the natural tolerance exhibited
      by most cotton, Gossypium hirsutum L., cultivars to the herbicide
      trifloxysulfuron sodium (TFS, CGA 362622, commercial formulation Envoke). A 1-bp
      frameshift insertion in the third exon of CYP749A16 results in the loss of
      tolerance to TFS. The DNA marker designed from this insertion perfectly co
      segregated with the phenotype in 2145 F2 progeny of a cross between the sensitive
      cultivar Paymaster HS26 and tolerant cultivar Stoneville 474, and in 550
      recombinant inbred lines of a multi-parent advanced generation inter-cross
      population. Marker analysis of 382 additional cotton cultivars identified twelve
      cultivars containing the 1-bp frameshift insertion. The marker genotypes matched
      perfectly with phenotypes in 188 plants from the selected twelve cultivars. Virus
      induced gene silencing of CYP749A16 generated sensitivity in the tolerant cotton
      cultivar Stoneville 474. CONCLUSIONS: CYP749A16 located on chromosome D10 is
      required for TFS herbicide tolerance in cotton. This finding should add to the
      repertoire of tools available to farmers and breeders for the advancement of
      agricultural productivity.

PMID- 30200873
TI  - Changing expression profiles of long non-coding RNAs, mRNAs and circular RNAs in
      ethylene glycol-induced kidney calculi rats.
AB  - BACKGROUND: To explore long non-coding RNA (lncRNA), mRNA and circular RNA
      (circRNA) expression profiles and their biological functions in the pathogenesis
      of kidney stones in ethylene glycol-induced urolithiasis rats. RESULTS: The
      expression of 1440 lncRNAs, 2455 mRNAs and 145 circRNAs was altered in the
      kidneys of urolithiasis rats. GO and KEGG biological pathway analysis were
      performed to predict the functions of differentially expressed lncRNAs, circRNAs
      and co-expressed potential targeting genes. Co-expression networks of lncRNA-mRNA
      and circRNA-miRNA were constructed based on correlation analysis between
      differentially expressed RNAs. mRNAs coexpressed with lncRNAs were involved in
      many kidney diseases, e.g., Ephb6 was associated with the reabsorption ability of
      the kidney. Arl5b was associated with the dynamic changes in the podocyte foot
      process in podocyte injury. miRNAs co-expressed with circRNAs, such as rno-miR
      138-5p and rno-miR-672-5p, have been proven to be functional in hypercalciuria
      urolithiasis. CONCLUSION: The expression profile provided a systematic
      perspective on the potential functions of lncRNAs and circRNAs in the
      pathogenesis of kidney stones. Differentially expressed lncRNAs and circRNAs
      might serve as treatment targets for kidney stones.

PMID- 30200874
TI  - Linked open data-based framework for automatic biomedical ontology generation.
AB  - BACKGROUND: Fulfilling the vision of Semantic Web requires an accurate data model
      for organizing knowledge and sharing common understanding of the domain. Fitting
      this description, ontologies are the cornerstones of Semantic Web and can be used
      to solve many problems of clinical information and biomedical engineering, such
      as word sense disambiguation, semantic similarity, question answering, ontology
      alignment, etc. Manual construction of ontology is labor intensive and requires
      domain experts and ontology engineers. To downsize the labor-intensive nature of
      ontology generation and minimize the need for domain experts, we present a novel
      automated ontology generation framework, Linked Open Data approach for Automatic
      Biomedical Ontology Generation (LOD-ABOG), which is empowered by Linked Open Data
      (LOD). LOD-ABOG performs concept extraction using knowledge base mainly UMLS and
      LOD, along with Natural Language Processing (NLP) operations; and applies
      relation extraction using LOD, Breadth first Search (BSF) graph method, and
      Freepal repository patterns. RESULTS: Our evaluation shows improved results in
      most of the tasks of ontology generation compared to those obtained by existing
      frameworks. We evaluated the performance of individual tasks (modules) of
      proposed framework using CDR and SemMedDB datasets. For concept extraction,
      evaluation shows an average F-measure of 58.12% for CDR corpus and 81.68% for
      SemMedDB; F-measure of 65.26% and 77.44% for biomedical taxonomic relation
      extraction using datasets of CDR and SemMedDB, respectively; and F-measure of
      52.78% and 58.12% for biomedical non-taxonomic relation extraction using CDR
      corpus and SemMedDB, respectively. Additionally, the comparison with manually
      constructed baseline Alzheimer ontology shows F-measure of 72.48% in terms of
      concepts detection, 76.27% in relation extraction, and 83.28% in property
      extraction. Also, we compared our proposed framework with ontology-learning
      framework called "OntoGain" which shows that LOD-ABOG performs 14.76% better in
      terms of relation extraction. CONCLUSION: This paper has presented LOD-ABOG
      framework which shows that current LOD sources and technologies are a promising
      solution to automate the process of biomedical ontology generation and extract
      relations to a greater extent. In addition, unlike existing frameworks which
      require domain experts in ontology development process, the proposed approach
      requires involvement of them only for improvement purpose at the end of ontology
      life cycle.

PMID- 30200875
TI  - Correction to: The M-phase specific hyperphosphorylation of Staufen2 involved the
      cyclin-dependent kinase CDK1.
AB  - Following publication of the original article [1], the authors reported a change
      to one of the author names.

PMID- 30200876
TI  - Differences in the digestive enzyme activity, intestinal mucosa and microbial
      community in loach cultivated in two separate environments.
AB  - BACKGROUND: Fish culture in rice paddies can contribute to increasing yields of
      rice and surplus fish products. Environmental impacts and food-safety issues have
      become important topics in aquaculture, and organic foods currently were paid
      attention by researchers and industry practitioners. But the mechanism of
      differences in quality of Loach (Paramisgurnus dabryanus) reared in rice fields
      and ponds remains largely uncharacterized. In this study,digestive enzyme
      activity, intestinal mucosa cells and the gut microbial community of loach were
      determined under the two separate cultivation modes. RESULTS: The levels of
      intestinal digestive enzyme activity of fish reared in the paddy-cultivated mode
      (PACM) were higher (P < 0.05) than those in the pond-cultivated mode (POCM). It
      was extremely significant (P < 0.01) for the activity of lipase in the liver,
      foregut and midgut, and for the activities of amylase and trypsin in the hindgut.
      Acid mucous cells in the loach foregut in PACM were fewer than in POCM (P <
      0.01). In summer, the abundance of the Firmicutes, Lactobacillus spp., Aeromonas
      hydrophila, Enterobacteriaceae and Streptococcus spp. in loach intestinal mucosa
      in PACM was higher than in POCM. In fall, the abundance of total bacteria, the
      Bacteroidetes, Bifidobacterium and Enterobacteriaceae in the intestinal mucosa in
      PACM was likewise higher than in POCM. These differences were significant (P <
      0.05 or P < 0.01) between loach in the two separate culture modes for all
      microorganisms except for A. hydrophila and Streptococcus spp. In addition,
      quantitative PCR assays showed that some microorganisms presented consistently
      similar abundances in the gut as in the culture water. CONCLUSIONS: These results
      showed some enzymatic activities involved in digestion in liver and intestine of
      loach in PACM were higher than those in POCM, as using digestive enzyme analysis
      and histological observation of intestinal sections. These findings suggest most
      of the microorganisms examined in the gut mucosa of loach in the two culture
      modes significantly differed in abundance between summer and fall. However, some
      pathogenic bacteria in the gut, particularly A. hydrophila, presented lower
      abundance in PACM in fall, yet did not differ in abundance between loach in the
      two cultivation modes.

PMID- 30200877
TI  - Enhancer reprogramming in mammalian genomes.
AB  - BACKGROUND: Transcription factor binding site (TFBS) loss, gain, and reshuffling
      within the sequence of a regulatory element could alter the function of that
      regulatory element. Some of the changes will be detrimental to the fitness of the
      species and will result in gradual removal from a population, while other changes
      would be either beneficial or just a part of genetic drift and end up being fixed
      in a population. This "reprogramming" of regulatory elements results in
      modification of the gene regulatory landscape during evolution. RESULTS: We
      identified reprogrammed enhancers (RPEs) by comparing the distribution of tissue
      specific enhancers in the human and mouse genomes. We observed that around 30% of
      mammalian enhancers have been reprogrammed after the human-mouse speciation. In
      79% of cases, the reprogramming of an enhancer resulted in a quantifiably
      different expression of a flanking gene. In the case of the Thy-1 cell surface
      antigen gene, for example, enhancer reprogramming is associated with cortex to
      thymus change in gene expression. To understand the mechanisms of enhancer
      reprogramming, we profiled the evolutionary changes in the TFBS enhancer content
      and found that enhancer reprogramming took place through the acquisition of new
      TFBSs in 72% of reprogramming events. CONCLUSIONS: Our results suggest that
      enhancer reprogramming takes place within well-established regulatory loci with
      RPEs contributing additively to fine-tuning of the gene regulatory program in
      mammals. We also found evidence for acquisition of novel gene function through
      enhancer reprogramming, which allows expansion of gene regulatory landscapes into
      new regulatory domains.

PMID- 30200878
TI  - Chronic dexamethasone exposure retards growth without altering the digestive
      tract microbiota composition in goats.
AB  - BACKGROUND: Dexamethasone (Dex), an artificially synthetic cortisol substitute,
      is commonly used as an anti-inflammatory drug, and is also employed to mimic the
      stress state experimentally. It is well known that chronic stress disturbs the
      gut microbiota community and digestive functions. However, no relevant studies
      have been conducted in ruminants. RESULTS: In this study, a low dosage of Dex
      (0.2 mg/kg body weight, Dex group, n = 5) was consecutively injected
      intramuscularly for 21 days to simulate chronic stress in growing goats. Goats
      were injected with saline (0.2 mg/kg body weight) as the control group (Con, n =
      5). Dex-treated goats showed a higher number of white blood cells and blood
      glucose levels (p < 0.01), but lower dry matter intake (DMI) and body weight (p <
      0.01) than those of saline-injected goats. Plasma cortisol concentration
      decreased significantly in response to the Dex injection compared to the control
      (p < 0.05). The Dex treatment did not change most ruminal volatile fatty acid
      (VFAs) concentrations before the morning feeding after 1-21 days of treatment (p
      > 0.05); however, ruminal VFA concentrations decreased dramatically 2, 4, 6, and
      8 h after the morning feeding on day 21 of the Dex injections. In this study,
      chronic Dex exposure did not alter the community structure of microbes or
      methanogenes in the rumen, caecum, or colonic digesta. Only Prevotella increased
      on days 7 and 14 of Dex treatment, but decreased on day 21, and Methanosphaera
      was the only genus of methanogene that decreased. CONCLUSIONS: Our results
      suggest that chronic Dex exposure retards growth by decreasing DMI, which may be
      mediated by higher levels of blood glucose and lower ruminal VFA production.
      Microbiota in the digestive tract was highly resistant to chronic Dex exposure.

PMID- 30200879
TI  - Identification of differentially expressed genes by means of outlier detection.
AB  - BACKGROUND: An important issue in microarray data is to select, from thousands of
      genes, a small number of informative differentially expressed (DE) genes which
      may be key elements for a disease. If each gene is analyzed individually, there
      is a big number of hypotheses to test and a multiple comparison correction method
      must be used. Consequently, the resulting cut-off value may be too small.
      Moreover, an important issue is the selection's replicability of the DE genes. We
      present a new method, called ORdensity, to obtain a reproducible selection of DE
      genes. It takes into account the relation between all genes and it is not a gene
      by-gene approach, unlike the usually applied techniques to DE gene selection.
      RESULTS: The proposed method returns three measures, related to the concepts of
      outlier and density of false positives in a neighbourhood, which allow us to
      identify the DE genes with high classification accuracy. To assess the
      performance of ORdensity, we used simulated microarray data and four real
      microarray cancer data sets. The results indicated that the method correctly
      detects the DE genes; it is competitive with other well accepted methods; the
      list of DE genes that it obtains is useful for the correct classification or
      diagnosis of new future samples and, in general, it is more stable than other
      procedures. CONCLUSIONS: ORdensity is a new method for identifying DE genes that
      avoids some of the shortcomings of the individual gene identification and it is
      stable when the original sample is changed by subsamples.

PMID- 30200881
TI  - Phylogenomic evidence for ancient recombination between plastid genomes of the
      Cupressus-Juniperus-Xanthocyparis complex (Cupressaceae).
AB  - BACKGROUND: Phylogenetic relationships among Eastern Hemisphere cypresses,
      Western Hemisphere cypresses, junipers, and their closest relatives are
      controversial, and generic delimitations have been in flux for the past decade.
      To address relationships and attempt to produce a more robust classification, we
      sequenced 11 new plastid genomes (plastomes) from the five variously described
      genera in this complex (Callitropsis, Cupressus, Hesperocyparis, Juniperus, and
      Xanthocyparis) and compared them with additional plastomes from diverse members
      of Cupressaceae. RESULTS: Phylogenetic analysis of protein-coding genes recovered
      a topology in which Juniperus is sister to Cupressus, whereas a tree based on
      whole plastomes indicated that the Callitropsis-Hesperocyparis-Xanthocyparis
      (CaHX) clade is sister to Cupressus. A sliding window analysis of site-specific
      phylogenetic support identified a ~ 15 kb region, spanning the genes ycf1 and
      ycf2, which harbored an anomalous signal relative to the rest of the genome.
      After excluding these genes, trees based on the remainder of the genes and genome
      consistently recovered a topology grouping the CaHX clade and Cupressus with
      strong bootstrap support. In contrast, trees based on the ycf1 and ycf2 region
      strongly supported a sister relationship between Cupressus and Juniperus.
      CONCLUSIONS: These results demonstrate that standard phylogenomic analyses can
      result in strongly supported but conflicting trees. We suggest that the
      conflicting plastomic signals result from an ancient introgression event
      involving ycf1 and ycf2 that occurred in an ancestor of this species complex. The
      introgression event was facilitated by plastomic recombination in an ancestral
      heteroplasmic individual carrying distinct plastid haplotypes, offering further
      evidence that recombination occurs between plastomes. Finally, we provide strong
      support for previous proposals to recognize five genera in this species complex:
      Callitropsis, Cupressus, Hesperocyparis, Juniperus, and Xanthocyparis.

PMID- 30200880
TI  - Value of the fT3/fT4 ratio and its combination with the GRACE risk score in
      predicting the prognosis in euthyroid patients with acute myocardial infarction
      undergoing percutaneous coronary intervention: a prospective cohort study.
AB  - BACKGROUND: Thyroid hormones deeply influence the cardiovascular system; however,
      the association between the fT3/fT4 ratio and the clinical outcome in euthyroid
      patients with acute myocardial infarction (AMI) undergoing percutaneous coronary
      intervention (PCI) is not well defined. Therefore, the present study aimed to
      assess the prognostic performance of the fT3/fT4 ratio in predicting the long
      term prognosis in euthyroid patients with AMI undergoing PCI. METHODS: In a
      prospective cohort study with a 1-year follow-up, according to the clinical end
      point, 953 euthyroid individuals (61.0 +/- 11.6; female, 25.8%) were divided into
      two groups: (1) the survival group (n = 915) and (2) the death group (n = 38).
      RESULTS: According to Cox regression multivariate analysis, fT4 (HR: 1.249, 95%
      CI: 1.053-1.480, p = 0.010) and the fT3/fT4 ratio (HR: 3.546, 95% CI: 1.705
      7.377, p = 0.001) were associated with an increased risk of 1-year all-cause
      mortality. The prognostic performance of the fT3/fT4 ratio was similar to the
      Global Registry of Acute Coronary Events (GRACE) score in predicting 1-year all
      cause mortality (C-statistic: z = 0.261, p = 0.794; IDI: -0.017, p = 0.452; NRI: 
      0.049, p = 0.766), but better than fT4 (C-statistic: z = 2.438, p = 0.015; IDI:
      0.053, p = 0.002; NRI: 0.656, p < 0.001). The fT3/fT4 ratio also significantly
      improved the prognostic performance of the GRACE score (GRACE score vs GRACE
      score + fT3/fT4 ratio: C-statistic: z = 2.116, p = 0.034; IDI: 0.0415, p = 0.007;
      NRI: 0.614, p < 0.001). CONCLUSIONS: In euthyroid patients with AMI undergoing
      PCI, the fT3/fT4 ratio was an independent predictor of 1-year all-cause
      mortality. Its prognostic performance was similar to the GRACE score, and also
      improved its prognostic performance (GRACE score vs GRACE score + fT3/fT4 ratio).

PMID- 30200882
TI  - Prevalence and risk factors of tungiasis among children of Wensho district,
      southern Ethiopia.
AB  - BACKGROUND: Tungiasis is an ectoparasitic infestation, which still has public
      health importance in deprived populations of developing countries. Data on the
      prevalence and risk factors of tungiasis is rare in Ethiopia. Hence, this study
      was designed to determine the prevalence and risk factors of tungiasis among
      children in Wensho district, southern Ethiopia. METHODS: From February to May
      2016, we conducted a community-based cross-sectional study on 366 children 5-14
      years old. Data about the presence and severity of tungiasis were obtained
      through inspection and data on risk factors were collected through interviews of
      parents/guardians of the children using structured questionnaire and through
      observation of the housing environment using structured checklist. RESULTS: Two
      hundred fifteen (58.7%, 95% confidence interval [CI]: 53.7%, 63.8%) of the 366
      children were infested with Tunga penetrans. Most lesions were localized in the
      feet and the distribution of the disease by sex was similar (57.4% among males
      and 60.3% among females). Children of illiterate mothers (adjusted odds ratio
      [AOR]: 3.62, 95% CI: 1.35, 9.73) and children whose mothers have attended only
      primary education (AOR: 2.72, 95% CI: 1.06, 6.97), children from cat owning
      households (AOR: 4.95, 95% CI: 1.19, 20.60) and children who occasionally use
      footwear (AOR: 7.42, 95% CI: 4.29, 12.83) and those who never use footwear (AOR:
      12.55, 95% CI: 3.38, 46.58) had a significantly higher odds of tungiasis
      infestation. CONCLUSION: Tungiasis is an important public health problem with
      considerable morbidity among children in Wensho. Hence, implementation of
      tungiasis prevention strategies such as promoting shoes wearing, provision of
      health education, fumigating the residential houses and applying insecticides on
      pets are recommended.

PMID- 30200883
TI  - Genomic characterization of Trichoderma atrobrunneum (T. harzianum species
      complex) ITEM 908: insight into the genetic endowment of a multi-target
      biocontrol strain.
AB  - BACKGROUND: So far, biocontrol agent selection has been performed mainly by time
      consuming in vitro confrontation tests followed by extensive trials in greenhouse
      and field. An alternative approach is offered by application of high-throughput
      techniques, which allow extensive screening and comparison among strains for
      desired genetic traits. In the genus Trichoderma, the past assignments of
      particular features or strains to one species need to be reconsidered according
      to the recent taxonomic revisions. Here we present the genome of a biocontrol
      strain formerly known as Trichoderma harzianum ITEM 908, which exhibits both
      growth promoting capabilities and antagonism against different fungal pathogens,
      including Fusarium graminearum, Rhizoctonia solani, and the root-knot nematode
      Meloidogyne incognita. By genomic analysis of ITEM 908 we investigated the
      occurrence and the relevance of genes associated to biocontrol and stress
      tolerance, providing a basis for future investigation aiming to unravel the
      complex relationships between genomic endowment and exhibited activities of this
      strain. RESULTS: The MLST analysis of ITS-TEF1 concatenated datasets reclassified
      ITEM 908 as T. atrobrunneum, a species recently described within the T. harzianum
      species complex and phylogenetically close to T. afroharzianum and T.
      guizhouense. Genomic analysis revealed the presence of a broad range of genes
      encoding for carbohydrate active enzymes (CAZYmes), proteins involved in
      secondary metabolites production, peptaboils, epidithiodioxopiperazines and
      siderophores potentially involved in parasitism, saprophytic degradation as well
      as in biocontrol and antagonistic activities. This abundance is comparable to
      other Trichoderma spp. in the T. harzianum species complex, but broader than in
      other biocontrol species and in the species T. reesei, known for its industrial
      application in cellulase production. Comparative analysis also demonstrated
      similar genomic organization of major secondary metabolites clusters, as in other
      Trichoderma species. CONCLUSIONS: Reported data provide a contribution to a
      deeper understanding of the mode of action and identification of activity
      specific genetic markers useful for selection and improvement of biocontrol
      strains. This work will also enlarge the availability of genomic data to perform
      comparative studies with the aim to correlate phenotypic differences with genetic
      diversity of Trichoderma species.

PMID- 30200884
TI  - Predictors for false-negative QuantiFERON-TB Gold assay results in patients with
      extrapulmonary tuberculosis.
AB  - BACKGROUNDS: Extrapulmonary tuberculosis (EPTB) is a heterogeneous disease, and
      diagnosis is sometimes difficult. We investigated the diagnostic performance of
      the QuantiFERON-TB Gold assay (QFT-GIT) according to sites of EPTB and predictors
      for false-negative QFT-GIT results. METHODS: A total of 2176 patients were
      registered with active TB from January 2012 to December 2016 in Seoul St. Mary's
      Hospital, a 1200-bed tertiary teaching hospital in Seoul, Korea. We
      retrospectively reviewed the medical records of 163 EPTB patients who underwent
      QFT-GIT. RESULTS: False negative QFT-GIT results were found in 28.8% (95% CI 0.22
      0.36) of patients with EPTB. In the proven TB group, negative QFT-GIT results
      were found in 28.6% (95% CI 0.04-0.71) of pleural, 8.3% 0.002-0.38of lymph node,
      8.3% (95% CI 0.002-0.38) of skeletal and 5.8% (95% CI 0.001-0.28) of
      gastrointestinal TB cases. Among probable TB cases, QFT-GIT negative results were
      identified in 46.2% (95% CI 0.19-0.75) of skeletal, 33.3% (95% CI 10-0.65) of
      pericardial, 30.8% (95% CI 0.09-0.61) of pleural and 17.2% (95% CI 0.10-0.56) of
      gastrointestinal TB cases. In the possible TB cases, central nervous system TB (n
      = 21) was most frequent, and 66.7% (95% CI 0.43-0.85) of those showed QFT-GIT
      negative results. By multivariate analysis, possible TB was independently
      associated with false-negative QFT-GIT results (OR 4.92, 95% CI 1.51-16.06, p =
      0.008). CONCLUSIONS: Prudent interpretation of QFT-GIT results might be needed
      according to anatomic site of involvement and diagnostic criteria in patients
      with high suspicion of EPTB.

PMID- 30200885
TI  - Root and leaf metabolite profiles analysis reveals the adaptive strategies to low
      potassium stress in barley.
AB  - BACKGROUND: Potassium (K) deficiency in arable land is one of the most important
      factors affecting crop productivity. Development of low K (LK) tolerant crop
      cultivars is regarded as a best economic and effective approach for solving the
      issue of LK. In previous studies, we found a wider variation of LK tolerance in
      the Tibetan wild barley accessions than cultivated barley. However, the mechanism
      of LK tolerance in wild barley is still elusive. RESULTS: In this study, two wild
      barley genotypes (XZ153, LK tolerant and XZ141, LK sensitive) and one cultivar
      (LuDaoMai, LK tolerant) was used to investigate metabolome changes in response to
      LK stress. Totally 57 kinds of metabolites were identified in roots and leaves of
      three genotypes at 16 d after LK treatment. In general, accumulation of amino
      acids and sugars was enhanced in both roots and leaves, while organic acids were
      reduced under LK stress compared to the control. Meanwhile, the concentrations of
      the negatively charged amino acids (Asp and Glu) and most organic acids was
      reduced in both roots and leaves, but more positively charged amino acids (Lys
      and Gln) were increased in three genotypes under LK. XZ153 had less reduction
      than other two genotypes in biomass and chlorophyll content under LK stress and
      showed greater antioxidant capacity as reflected by more synthesis of active
      oxygen scavengers. Higher LK tolerance of XZ153 may also be attributed to its
      less carbohydrate consumption and more storage of glucose and other sugars, thus
      providing more energy for plant growth under LK stress. Moreover, phenylpropanoid
      metabolic pathway mediated by PAL differed among three genotypes, which is
      closely associated with the genotypic difference in LK tolerance. CONCLUSIONS: LK
      tolerance in the wild barley is attributed to more active phenylpropanoid
      metabolic pathway mediated by PAL, energy use economy by reducing carbohydrate
      consumption and storage of glucose and other sugars, and higher antioxidant
      defense ability under LK stress.

PMID- 30200886
TI  - The transducer-like protein Tlp12 of Campylobacter jejuni is involved in
      glutamate and pyruvate chemotaxis.
AB  - BACKGROUND: Campylobacter jejuni is one of the most common bacterial causes of
      food-borne enteritis worldwide. Chemotaxis in C. jejuni is known to be critical
      for the successful colonization of the host and key for the adaptation of the
      microbial species to different host environments. In C. jejuni, chemotaxis is
      regulated by a complex interplay of 13 or even more different chemoreceptors,
      also known as transducer-like proteins (Tlps). Recently, a novel chemoreceptor
      gene, tlp12, was described and found to be present in 29.5% of the investigated
      C. jejuni strains. RESULTS: In this study, we present a functional analysis of
      Tlp12 with the aid of a tlp12 knockout mutant of the C. jejuni strain A17.
      Substrate specificity was investigated by capillary chemotaxis assays and
      revealed that Tlp12 plays an important role in chemotaxis towards glutamate and
      pyruvate. Moreover, the Deltatlp12 mutant shows increased swarming motility in
      soft agar assays, an enhanced invasion rate into Caco-2 cells and an increased
      autoagglutination rate. The growth rate was slightly reduced in the Deltatlp12
      mutant. The identified phenotypes were in partial restored by complementation
      with the wild type gene. Tlp12-harboring C. jejuni strains display a strong
      association with chicken, whose excreta are known to contain high glutamate
      levels. CONCLUSIONS: TLP12 is a chemoreceptor for glutamate and pyruvate
      recognition. Deletion of tlp12 has an influence on distinct physiological
      features, such as growth rate, swarming motility, autoagglutination and
      invasiveness.

PMID- 30200887
TI  - Genome-wide identification and expression analyses of the pectate lyase (PEL)
      gene family in cotton (Gossypium hirsutum L.).
AB  - BACKGROUND: Pectin is a major component and structural polysaccharide of the
      primary cell walls and middle lamella of higher plants. Pectate lyase (PEL, EC
      4.2.2.2), a cell wall modification enzyme, degrades de-esterified pectin for cell
      wall loosening, remodeling and rearrangement. Nevertheless, there have been few
      studies on PEL genes and no comprehensive analysis of the PEL gene family in
      cotton. RESULTS: We identified 53, 42 and 83 putative PEL genes in Gossypium
      raimondii (D5), Gossypium arboreum (A2), and Gossypium hirsutum (AD1),
      respectively. These PEL genes were classified into five subfamilies (I-V).
      Members from the same subfamilies showed relatively conserved gene structures,
      motifs and protein domains. An analysis of gene chromosomal locations and gene
      duplication revealed that segmental duplication likely contributed to the
      expansion of the GhPELs. The 2000 bp upstream sequences of all the GhPELs
      contained auxin response elements. A transcriptomic data analysis showed that 62
      GhPELs were expressed in various tissues. Notably, most (29/32) GhPELs of
      subfamily IV were preferentially expressed in the stamen, and five GhPELs of
      subfamily V were prominently expressed at the fiber elongation stage. In
      addition, qRT-PCR analysis revealed the expression characteristics of 24 GhPELs
      in four pollen developmental stages and significantly different expression of
      some GhPELs between long- and short-fiber cultivars. Moreover, some members were
      responsive to IAA treatment. The results indicate that GhPELs play significant
      and functionally diverse roles in the development of different tissues.
      CONCLUSIONS: In this study, we comprehensively analyzed PELs in G. hirsutum,
      providing a foundation to better understand the functions of GhPELs in different
      tissues and pathways, especially in pollen, fiber and the auxin signaling
      pathway.

PMID- 30200889
TI  - Single-trial dynamics explain magnitude sensitive decision making.
AB  - BACKGROUND: Previous research has reported or predicted, on the basis of
      theoretical and computational work, magnitude sensitive reaction times. Magnitude
      sensitivity can arise (1) as a function of single-trial dynamics and/or (2) as
      recent computational work has suggested, while single-trial dynamics may be
      magnitude insensitive, magnitude sensitivity could arise as a function of overall
      reward received which in turn affects the speed at which decision boundaries
      collapse, allowing faster responses as the overall reward received increases.
      RESULTS: Here, we review previous theoretical and empirical results and we
      present new evidence for magnitude sensitivity arising as a function of single
      trial dynamics. CONCLUSIONS: The result of magnitude sensitive reaction times
      reported is not compatible with single-trial magnitude insensitive models, such
      as the statistically optimal drift diffusion model.

PMID- 30200888
TI  - First molecular study in Lebanese patients with Cockayne syndrome and report of a
      novel mutation in ERCC8 gene.
AB  - BACKGROUND: Cockayne Syndrome (CS) is a rare autosomal recessive disorder
      characterized by neurological and sensorial impairment, dwarfism, microcephaly
      and photosensitivity. CS is caused by mutations in ERCC6 (CSB) or ERCC8 (CSA)
      genes. METHODS: Three patients with CS were referred to the Medical Genetics Unit
      of Saint Joseph University. Sanger sequencing of both ERCC8 and ERCC6 genes was
      performed: ERCC8 was tested in all patients while ERCC6 in one of them. RESULTS:
      Sequencing led to the identification of three homozygous mutations, two in ERCC8
      (p.Y322* and c.843 + 1G > C) and one in ERCC6 (p.R670W). All mutations were
      previously reported as pathogenic except for the c.843 + 1G > C splice site
      mutation in ERCC8 which is novel. CONCLUSIONS: Molecular diagnosis was
      established in all patients included in our study. A genotype-phenotype
      correlation is discussed and a link, between mutations and some specific
      religious communities in Lebanon, is suggested.

PMID- 30200890
TI  - Novel mutations in ALDH1A3 associated with autosomal recessive
      anophthalmia/microphthalmia, and review of the literature.
AB  - BACKGROUND: Autosomal recessive anophthalmia and microphthalmia are rare
      developmental eye defects occurring during early fetal development. Syndromic and
      non-syndromic forms of anophthalmia and microphthalmia demonstrate extensive
      genetic and allelic heterogeneity. To date, disease mutations have been
      identified in 29 causative genes associated with anophthalmia and microphthalmia,
      with autosomal dominant, autosomal recessive and X-linked inheritance patterns
      described. Biallelic ALDH1A3 gene variants are the leading genetic causes of
      autosomal recessive anophthalmia and microphthalmia in countries with frequent
      parental consanguinity. METHODS: This study describes genetic investigations in
      two consanguineous Pakistani families with a total of seven affected individuals
      with bilateral non-syndromic clinical anophthalmia. RESULTS: Using whole exome
      and Sanger sequencing, we identified two novel homozygous ALDH1A3 sequence
      variants as likely responsible for the condition in each family; missense
      mutation [NM_000693.3:c.1240G > C, p.Gly414Arg; Chr15:101447332G > C (GRCh37)] in
      exon 11 (family 1), and, a frameshift mutation [NM_000693.3:c.172dup,
      p.Glu58Glyfs*5; Chr15:101425544dup (GRCh37)] in exon 2 predicted to result in
      protein truncation (family 2). CONCLUSIONS: This study expands the molecular
      spectrum of pathogenic ALDH1A3 variants associated with anophthalmia and
      microphthalmia, and provides further insight of the key role of the ALDH1A3 in
      human eye development.

PMID- 30200891
TI  - Contamination of microbial pathogens and their antimicrobial pattern in operating
      theatres of peri-urban eastern Uganda: a cross-sectional study.
AB  - BACKGROUND: Microbial contamination of hospital environment, especially in
      operating theatres (OT) and other specialized units has greatly contributed to
      continuous and multiple exposure to nosocomial infections by patients and the
      public. We purposed to assess microbial contamination of operating theatres and
      antibacterial sensitivity pattern of bacteria isolated from theatres of Mbale
      Regional Referral Hospital, Eastern Uganda. METHODS: We employed a laboratory
      based cross-sectional study design. Swabbing of different surfaces and settle
      plate establishment in 4 various operating theatres was carried out. A total of
      109 samples were collected, 31 air samples and 78 swabs from four operating
      theatres. Samples were collected in the mornings after disinfection prior to
      start of daily operations. Antibacterial sensitivity testing of isolated
      bacterial pathogens was performed by Kirby Bauer disc diffusion method following
      standard operating procedure. Colony counts for the settle plates were carried
      out using a colony counter. RESULTS: All the four theatres had their mean colony
      counts exceeding the acceptable limit of 5 cfu/dm2/h. Gynaecology theatre had up
      to 261 cfu/dm2/h and Ophthalmology operating theatre had approximately 43
      cfu/dm2/h. A total of 14 different organisms were isolated with Pseudomonas spp.
      [23.9%]; Bacillus spp. [17.5%] and Aspergillus spp. [15.8%] being the most common
      contaminants respectively. Other isolates included Enterococcus spp., Rhizopus
      spp. and Coagulate Negative Staphylococcus isolates especially from settle
      plates. Most bacterial isolates showed considerable resistance to antibacterial
      agents. Pseudomonas spp. was resistant to chloramphenicol (53.6%) and
      cotrimoxazole (57.1%). Most of the bacterial pathogens were sensitive to imipenem
      [83.3%]. CONCLUSIONS: There is moderate contamination of operating theatres of
      Mbale Regional Referral Hospital. Common organisms were Pseudomonas, Bacillus,
      and Aspergillus spps. Resistance was observed against chloramphenicol and
      cotrimoxazole. More caution is necessary to carefully disinfect the operating
      theatres at Regional referral settings and similar tertiary health care centres
      with more emphasis on obstetrics and gynecology theatres. Diagnosis and care of
      patients at such clinical settings should consider the possibility of antibiotic
      resistance.

PMID- 30200892
TI  - The linear mitochondrial genome of the quarantine chytrid Synchytrium
      endobioticum; insights into the evolution and recent history of an obligate
      biotrophic plant pathogen.
AB  - BACKGROUND: Chytridiomycota species (chytrids) belong to a basal lineage in the
      fungal kingdom. Inhabiting terrestrial and aquatic environments, most are free
      living saprophytes but several species cause important diseases: e.g.
      Batrachochytrium dendrobatidis, responsible for worldwide amphibian decline; and
      Synchytrium endobioticum, causing potato wart disease. S. endobioticum has an
      obligate biotrophic lifestyle and isolates can be further characterized as
      pathotypes based on their virulence on a differential set of potato cultivars.
      Quarantine measures have been implemented globally to control the disease and
      prevent its spread. We used a comparative approach using chytrid mitogenomes to
      determine taxonomical relationships and to gain insights into the evolution and
      recent history of introductions of this plant pathogen. RESULTS: We assembled and
      annotated the complete mitochondrial genome of 30 S. endobioticum isolates and
      generated mitochondrial genomes for five additional chytrid species. The
      mitochondrial genome of S. endobioticum is linear with terminal inverted repeats
      which was validated by tailing and PCR amplifying the telomeric ends.
      Surprisingly, no conservation in organisation and orientation of mitochondrial
      genes was observed among the Chytridiomycota except for S. endobioticum and its
      sister species Synchytrium microbalum. However, the mitochondrial genome of S.
      microbalum is circular and comprises only a third of the 72.9 Kbp found for S.
      endobioticum suggesting recent linearization and expansion. Four mitochondrial
      lineages were identified in the S. endobioticum mitochondrial genomes. Several
      pathotypes occur in different lineages, suggesting that these have emerged
      independently. In addition, variations for polymorphic sites in the mitochondrial
      genome of individual isolates were observed demonstrating that S. endobioticum
      isolates represent a community of different genotypes. Such communities were
      shown to be complex and stable over time, but we also demonstrate that the use of
      semi-resistant potato cultivars triggers a rapid shift in the mitochondrial
      haplotype associated with increased virulence. CONCLUSIONS: Mitochondrial genomic
      variation shows that S. endobioticum has been introduced into Europe multiple
      times, that several pathotypes emerged multiple times, and that isolates
      represent communities of different genotypes. Our study represents the most
      comprehensive dataset of chytrid mitogenomes, which provides new insights into
      the extraordinary dynamics and evolution of mitochondrial genomes involving
      linearization, expansion and reshuffling.

PMID- 30200893
TI  - Exercise patterns in older adults instructed to follow moderate- or high
      intensity exercise protocol - the generation 100 study.
AB  - BACKGROUND: Making older adults exercise and keeping them in exercise programs is
      a major challenge. Understanding how older adults prefer to exercise may help
      developing tailored exercise programs and increase sustained exercise
      participation in ageing populations. We aimed to describe exercise patterns,
      including frequency, intensity, type, location and social setting of exercise, in
      older adults instructed to follow continuous moderate-intensity training (MCT) or
      high-intensity interval training (HIIT) over a one-year period. METHODS:
      Frequency, intensity, type, location and social setting (alone vs. together with
      others) of exercise were assessed using exercise logs from 618 older adults (aged
      70-77 years) randomized to MCT or HIIT. All participants completed exercise logs
      after each exercise session they performed during one year. Pearson Chi-square
      tests were run to assess the association between intensity, type, location and
      social setting of exercise with training group. RESULTS: Both groups performed
      2.2 +/- 1.3 exercise sessions per week during the year. Walking was the most
      common exercise type in both groups, but MCT had a higher proportion of walking
      sessions than HIIT (54.2% vs. 41.1%, p < 0.01). Compared to MCT, HIIT had a
      higher proportion of sessions with cycling (14.2% vs. 9.8%, p < 0.01), combined
      endurance and resistance training (10.3% vs. 7.5%, p < 0.01), jogging (6.5% vs.
      3.2%, p < 0.01) and swimming (2.6% vs. 1.7%, p < 0.01). Outdoors was the most
      common exercise location in both training groups (67.8 and 59.1% of all sessions
      in MCT and HIIT, respectively). Compared to MCT, HIIT had a higher proportion of
      sessions at a gym (21.4% vs. 17.5%, p < 0.01) and sports facility (9.8% vs. 7.6%,
      p < 0.01). Both groups performed an equal amount of sessions alone and together
      with others, but women had a higher proportion of sessions together with others
      compared to men (56% vs. 44%, p < 0.01). CONCLUSION: This is the first study that
      has followed older adults instructed to perform MCT or HIIT over a one-year
      period, collected data from each exercise session they performed and provided
      important knowledge about their exercise patterns. This novel information may
      help researchers and clinicians to develop tailored exercise programs in an
      ageing population.

PMID- 30200894
TI  - Associations between patient clinical characteristics and the presence of
      cytomegalovirus DNA in the bronchoalveolar lavage fluid of children with
      recurrent wheezing.
AB  - BACKGROUND: This study aimed to investigate the occurrence of Cytomegalovirus
      (CMV) DNA in the Bronchoalveolar lavage fluid (BALF) of children with recurrent
      wheezing and to identify associations with certain patient clinical
      characteristics. METHODS: In this cross-sectional study, pediatric patients (age
      < 36 months) admitted to Soochow University Hospital with recurrent wheezing (>=
      4 episodes of wheezing per year) were enrolled in the study. Cytomegalovirus DNA
      from their BALF was detected by real-time PCR. Subpopulations of blood
      immunoglobulins and T lymphocytes were quantified. The clinical characteristics
      of patients with and without BALF CMV DNA were compared. Comparisons of non
      normally distributed continuous variables between groups were made using the Mann
      Whitney U-test. Comparisons of frequency distributions were made using the Chi
      squared test. Spearman's rank correlation coefficient was used to evaluate
      correlations between the number of CMV DNA copies and continuous variables.
      RESULTS: A total of 111 patients aged 4 to 36 months (median 14.0 (IQR 8.0-22.0)
      months) were enrolled on to the study. Cytomegalovirus DNA was detected in 51.4%
      of patients (n = 111) with recurrent wheeze and was more prevalent among those
      aged 12 to 36 months with a positive modified asthma predictive index (mAPI) (n =
      38, median 23.5 (IQR 19.7-31.2) months) than in those of the same age group with
      a negative mAPI (n = 25, median 15.0 (IQR 13.0-19.0) months) (57.9% vs. 20.0%, p
      = 0.003). Bronchoalveolar lavage fluid CMV DNA copy number [median 7560 (IQR 1200
      71,150) copies/mL] was positively correlated with the duration of hospitalization
      (r = 0.33, p = 0.013), and negatively correlated with patient age (r = - 0.41, p
      = 0.002) and the percentage of BALF eosinophils (r = - 0.38, p = 0.004).
      CONCLUSIONS: CMV infection or reactivation in children with recurrent wheeze is
      associated with certain clinical characteristics, including younger age and lower
      levels of BALF eosinophils. Higher CMV DNA copy numbers were associated with a
      longer duration of hospitalization. Further studies are needed to address whether
      specific antiviral treatment could be beneficial for BALF CMV positive patients.

PMID- 30200895
TI  - Study protocol: high-dose mizoribine with prednisolone therapy in short-term
      relapsing steroid-sensitive nephrotic syndrome to prevent frequent relapse
      (JSKDC05 trial).
AB  - BACKGROUND: Eighty percent of children with steroid-sensitive nephrotic syndrome
      (SSNS) relapse within 2 years and 40-50% patients show frequently-relapsing
      nephrotic syndrome (FRNS). Patients showing a relapse within 6 months after
      initial remission are at high risk of FRNS. Since frequent prednisolone treatment
      for FRNS induces severe prednisolone side effects, development of a treatment to
      prevent patients from shifting to FRNS is desirable. Mizoribine is an
      immunosuppressive drug with fewer side effects than prednisolone. Recent studies
      reported the efficacy of high-dose mizoribine in children with FRNS.
      METHODS/DESIGN: We conduct a multicenter, open, randomized controlled trial to
      investigate the efficacy and safety of standard prednisolone plus high-dose
      mizoribine therapy in children with SSNS showing a relapse within 6 months after
      an initial remission. Patients are allocated to either standard prednisolone
      alone treatment group, or standard prednisolone plus high-dose mizoribine group.
      For the former group, mizoribine is administered at a dose of 10 mg/kg/day once
      daily and continued for 2 years. The primary endpoint is the duration to frequent
      relapse. DISCUSSION: The results provide important data on use of high-dose
      mizoribine to prevent SSNS patients from shifting to FRNS. Since blood
      concentrations of mizoribine have not been investigated in detail until now,
      there is a possibility that mizoribine is underestimated in favor of other
      immunosuppressive drugs. In future, high-dose mizoribine therapy may lead to
      prevention of relapse in children at high risk of FRNS, and to decreased total
      dose of prednisolone. TRIAL REGISTRATION: UMIN000005103 , (Prospectively
      registered 1st March 2011).

PMID- 30200898
TI  - Paraneoplastic immunoglobulin A nephropathy and associated focal segmental
      glomerulosclerosis in asymptomatic low volume B-cell lymphoma - a case report.
AB  - BACKGROUND: Paraneoplastic glomerulonephritis is rare in haematological
      malignancies and tends to manifest as minimal change disease, membranous
      glomerulonephritis or membranoproliferative glomerulonephritis. We present the
      first report of immunoglobulin A nephropathy and associated focal segmental
      glomerulosclerosis in a patient with asymptomatic low grade B-cell lymphoma. CASE
      PRESENTATION: A 53 year old gentleman presented with nephrotic range proteinuria
      (urine protein creatinine ratio of 662 mg/mmol) on a background of type 2
      diabetes mellitus (glycosylated haemoglobin: < 6%), hypertension, obesity (body
      mass index: 47.6 kg/m2) and degenerative spine disease. Bone marrow biopsy
      diagnosed a low grade B-cell lymphoma and renal biopsy was consistent with
      immunoglobulin A nephropathy. Lymphoma treatment with six cycles of
      cyclophosphamide/ rituximab/ prednisolone led to normalisation of urinary protein
      excretion (urine protein creatinine ratio: 14 mg/mmol at 26 months post
      chemotherapy). CONCLUSION: Paraneoplastic immunoglobulin A nephropathy can occur
      with a broad range of haematological malignancies regardless of stage. This case
      illustrates the importance of meticulous haematological system work-up for
      patients presenting with immunoglobulin A nephropathy. Recognition of
      paraneoplastic immunoglobulin A nephropathy and early diagnosis of associated
      malignancy can be life-saving.

PMID- 30200899
TI  - Coping with dementia caregiving: a mixed-methods study on feasibility and
      benefits of a psycho-educative group program.
AB  - BACKGROUND: Persons with dementia experience a progressive decline associated
      with an increasing dependency. Most of the support they require to stay at home
      comes from their informal caregivers (IC). Dementia informal caregiving imposes
      high costs on IC's health and quality of life, related to long periods of chronic
      stress. Based on evidence that more adequate coping strategies can reduce chronic
      stress and its negative consequences, and that psycho-educative interventions
      have the broadest effects on IC quality of life, the program "Learning to feel
      better... and help better" was developed in French-speaking Canada. This group
      intervention focusing on coping with the daily stress of dementia caregiving
      showed efficacy in decreasing the behavior problems of the person with dementia
      and the associated stress reactions in their IC. The objectives of our study were
      to examine within a one group pre- and post-test design 1) the feasibility of
      implementing the program in two regions of French-speaking Switzerland, 2) the
      effects of the program, and 3) the participants' use of the trained strategies in
      daily life. METHOD: A mixed-methods concurrent nested design was used to
      quantitatively evaluate the feasibility, the effects on five core outcomes, and
      strategy use in daily life. Additional qualitative data documented in depth the
      acceptability and impact of the intervention. RESULTS: We analyzed 18 complete
      data sets. Regarding feasibility, qualitative and quantitative results converged
      towards a very good acceptance of the program and a strong implication of the
      participants. Regarding effects, the program resulted in substantial and
      significant improvements in burden (d = 0.41, p < .05), psychological distress (d
      = 0.54, p < .05) and self-efficacy (d = 0.43, p < .05). The qualitative results
      emphasized the benefits of a group format: Participants felt understood by peers,
      could build new social bonds and experienced reduced social isolation. Data
      regularly collected in daily life showed that participants were using more and
      more over time the strategies they learned (beta01 = 0.55, p < .001),
      particularly reframing. CONCLUSION: This study expands on the original one
      conducted by the developers of the program in French-speaking Canada, by showing
      the feasibility and the very promising effects of this intervention in two
      regions of French-speaking Switzerland.

PMID- 30200897
TI  - Upper respiratory infections in a rural area with reduced malaria transmission in
      Senegal: a pathogens community study.
AB  - BACKGROUND: Acute Respiratory Infections (ARI) are common causes of febrile
      illnesses in many settings in Senegal. These infections are usually managed
      presumptively due to lack of appropriate diagnostic tools. This situation, can
      lead to poor management of febrile illness or antibiotic misuse. In addition,
      there are limited data on the spectrum of pathogens commonly responsible for
      these ARI. This study was conducted to explore the pathogens community among
      patients with acute respiratory infection in a rural area in Senegal. METHODS: A
      cross sectional study was conducted from August to December 2015. Children and
      adult patients attending Keur Soce health post for signs suggestive of acute
      respiratory infection were enrolled after providing inform consent. Eligible
      participants were recruited using a consecutive sampling method. Paired nose and
      throat swabs were collected for pathogen detection. Samples were processed using
      a multiplex PCR designed to identify 21 pathogens including both virus and
      bacteria. RESULTS: Two hundred and fifty patients participated in the study.
      Samples positivity rate was evaluated at 95.2% (238/250). Streptococcus
      pneumoniae was the predominant pathogen (74%) and was present in all months and
      all age-groups, followed by Staphylococcus aureus (28,8%) and rhinovirus (28,4%).
      Respiratory syncytial virus (RSV) was detected only among children under 5 years
      old in August and September while coronavirus was present in all age groups,
      during the months of October and December. CONCLUSION: This pilot study revealed
      a diversity of pathogens over the time and across all age groups, highlighting
      the need for further exploration. A pathogen community approach including both
      virus and bacteria at a larger scale becomes crucial for a better understanding
      of transmission dynamics at population level in order to help shape ARI control
      strategies.

PMID- 30200896
TI  - Harmonization of delirium severity instruments: a comparison of the DRS-R-98,
      MDAS, and CAM-S using item response theory.
AB  - BACKGROUND: This study aimed to describe the level of agreement of three commonly
      used delirium instruments: the Delirium Rating Scale-Revised-98 (DRS-R-98),
      Memorial Delirium Assessment Scale (MDAS), and Confusion Assessment Method
      Severity (CAM-S). METHODS: We used data from a prospective clinical research
      study, in which a team of trained lay interviewers administered each instrument
      along with supporting interview and cognitive assessments in the same group of
      patients daily while in the hospital (N = 352). We used item response theory
      methods to co-calibrate the instruments. RESULTS: The latent traits underlying
      the three measures, capturing the severity of a delirium assessment, had a high
      degree of correlation (r's > .82). Unidimensional factor models fit well,
      facilitating co-calibration of the instruments. Across instruments, the less
      intense symptoms were generally items reflecting cognitive impairment. Although
      the intensity of delirium severity for most in the sample was relatively low,
      many of the item thresholds for the delirium severity scales are high (i.e., in
      the more severe range of the latent ability distribution). This indicates that
      even people with severe delirium may have a low probability of endorsing the
      highest severity categories for many items. Co-calibration enabled us to derive
      crosswalks to map delirium severity scores among the delirium instruments.
      CONCLUSION: These delirium instruments measure the same underlying construct of
      delirium severity. Relative locations of items may inform design of refined
      measurement instruments. Mapping of overall delirium severity scores across the
      delirium severity instruments enabled us to derive crosswalks, which allow scores
      to be translated across instruments, facilitating comparison and combination of
      delirium studies for integrative analysis.

PMID- 30200900
TI  - Malignancy rates of B3-lesions in breast magnetic resonance imaging - do all
      lesions have to be excised?
AB  - BACKGROUND: Approximately 10% of all MRI-guided vacuum-assisted breast biopsies
      (MR-VAB) are histologically classified as B3 lesions. In most of these cases
      surgical excision is recommended. The aim of our study was to evaluate the
      malignancy rates of different B3 lesions which are visible on MRI to allow a
      lesion-adapted recommendation of further procedure. METHODS: Retrospective
      analysis of 572 consecutive MR-VAB was performed. Inclusion criteria were a
      representative (=successful) MR-VAB, histologic diagnosis of a B3 lesion and
      either the existence of a definite histology after surgical excision or proof of
      stability or regression of the lesion on follow-up MRI. Malignancy rates were
      evaluated for different histologies of B3 lesions. Lesion size and lesion
      morphology (mass/non-mass enhancement) on MRI were correlated with malignancy.
      RESULTS: Of all MR-VAB 43 lesions fulfilled the inclusion criteria. The
      malignancy rate of those B3 lesions was 23.3% (10/43). The highest malignancy
      rate was found in atypical ductal hyperplasia (ADH) lesions (50.0%; 4/8), 33.3%
      (2/6) in flat epithelial atypia (FEA), 28.6% (2/7) in lobular intraepithelial
      neoplasia (LIN) and 12.5% (2/16) in papillary lesions (PL). All 6 complex
      sclerosing lesions were benign. Mass findings were significantly more frequently
      malignant (31.3%, 10/32; p < 0.05) than non-mass findings (0/11). Small lesions
      measuring 5-10 mm were most often malignant (35.0%; 7/20). All large lesions (>
      20 mm) were not malignant (0/10). Intermediate sized lesions (11-20 mm) turned
      out to be malignant in 23.1% (3/13). CONCLUSIONS: The malignancy rate of B3
      lesions which were diagnosed after MR-VAB was 23.3%. ADH, FEA and LIN showed
      considerable malignancy rates (50%, 33% and 29%) and should therefore undergo
      surgical excision. None of the cases, which were diagnosed as radial scars, non
      mass enhancement or larger lesions (> 20 mm) were malignant. Here, a follow-up
      MRI seems to be advisable to avoid unnecessary operations. TRIAL REGISTRATION:
      Retrospective study design, waived by the IRB.

PMID- 30200901
TI  - SuperNoder: a tool to discover over-represented modular structures in networks.
AB  - BACKGROUND: Networks whose nodes have labels can seem complex. Fortunately, many
      have substructures that occur often ("motifs"). A societal example of a motif
      might be a household. Replacing such motifs by named supernodes reduces the
      complexity of the network and can bring out insightful features. Doing so
      repeatedly may give hints about higher level structures of the network. We call
      this recursive process Recursive Supernode Extraction. RESULTS: This paper
      describes algorithms and a tool to discover disjoint (i.e. non-overlapping)
      motifs in a network, replacing those motifs by new nodes, and then recursing. We
      show applications in food-web and protein-protein interaction (PPI) networks
      where our methods reduce the complexity of the network and yield insights.
      CONCLUSIONS: SuperNoder is a web-based and standalone tool which enables the
      simplification of big graphs based on the reduction of high frequency motifs. It
      applies various strategies for identifying disjoint motifs with the goal of
      enhancing the understandability of networks.

PMID- 30200902
TI  - The subtleties of cognitive decline in multiple sclerosis: an exploratory study
      using hierarchichal cluster analysis of CANTAB results.
AB  - BACKGROUND: It is essential to investigate cognitive deficits in multiple
      sclerosis (MS) to develop evidence-based cognitive rehabilitation strategies.
      Here we refined cognitive decline assessment using the automated tests of the
      Cambridge Neuropsychological Test Automated Battery (CANTAB) and hierarchical
      cluster analysis. METHODS: We searched for groups of distinct cognitive profiles
      in 35 relapsing-remitting MS outpatients and 32 healthy controls. All individuals
      participated in an automated assessment (CANTAB) and in a pencil and paper
      general neuropsychological evaluation. RESULTS: Hierarchical cluster analysis of
      the CANTAB results revealed two distinct groups of patients based mainly on the
      Simple Reaction Time (RTI) and on the Mean Latency of Rapid Visual Processing
      (RVP). The general neuropsychological assessment did not show any statistically
      significant differences between the cluster groups. Compared to the healthy
      control group, all MS outpatients had lower scores for RTI, RVP, paired associate
      learning, and delayed matching to sample. We also analyzed the associations
      between CANTAB results and age, education, sex, pharmacological treatment,
      physical activity, employment status, and the Expanded Disability Status Scale
      (EDSS). Although limited by the small number of observations, our findings
      suggest a weak correlation between performance on the CANTAB and age, education,
      and EDSS scores. CONCLUSIONS: We suggest that the use of selected large-scale
      automated visuospatial tests from the CANTAB in combination with multivariate
      statistical analyses may reveal subtle and earlier changes in information
      processing speed and cognition. This may expand our ability to define the limits
      between normal and impaired cognition in patients with Multiple Sclerosis.

PMID- 30200903
TI  - The preoperative prognostic nutritional index is a predictive and prognostic
      factor of high-grade serous ovarian cancer.
AB  - BACKGROUND: The aim of our study was to investigate whether an inflammation-based
      prognostic score, the prognostic nutritional index (PNI), was associated with
      clinical characteristics and prognosis in patients with high-grade serous ovarian
      cancer (HGSC). METHODS: We retrospectively investigated 875 patients who
      underwent primary staging or debulking surgery for HGSC between April 2005 and
      June 2013 at our institution. None of these patients received neoadjuvant
      chemotherapy. Preoperative PNI was calculated as serum albumin (g/L) + 0.005 *
      lymphocyte count (per mm3). The optimal PNI cutoff value for overall survival
      (OS) was identified using the online tool "Cutoff Finder". Clinical
      characteristics and PNI were compared with chi-square or Fisher's exact tests, as
      appropriate. The impact of PNI on OS was analyzed using the Kaplan-Meier method
      and Cox proportional hazards model. RESULTS: The median (range) PNI was 46.2
      (29.2-67.7). The 45.45 cutoff value discriminated patients into the high-PNI and
      low-PNI groups. A low preoperative PNI was associated with an advanced FIGO
      stage, increased CA125 level, more extensive ascites, residual disease and
      platinum resistance. For univariate analyses, a high PNI was associated with
      increased OS (p < 0.001). In multivariate analyses, the PNI remained an
      independent predictor of OS as a continuous variable (p = 0.021) but not as
      dichotomized groups (p = 0.346). CONCLUSION: Our study demonstrated that the PNI
      could be a predictive and prognostic parameter for HGSC.

PMID- 30200904
TI  - The 'Be Cancer Alert Campaign': protocol to evaluate a mass media campaign to
      raise awareness about breast and colorectal cancer in Malaysia.
AB  - BACKGROUND: Breast and colorectal cancer are the two most common cancers in
      Malaysia. Low awareness coupled with stigma and erroneous beliefs delay help
      seeking behaviours, lead to late presentation and contribute to poor detection
      rates. Promoting cancer awareness through mass media may be effective in
      improving cancer-related knowledge and uptake in screening tests. However,
      research is sparse regarding the cultural translation and implementation of mass
      media campaigns in Malaysia (and Asia) in terms of raising awareness about
      colorectal and breast cancer. METHODS: A collaborative partnership comprising
      researchers from Malaysia and the UK as well as policy makers, public health
      experts and non-government organisations from Malaysia was formed to design,
      deliver and evaluate the Be Cancer Alert Campaign. Each awareness-raising
      campaign will run for five weeks (Colorectal Cancer in April 2018, followed by
      Breast Cancer in October 2018). Evaluation of the campaigns will take place in
      Gombak district (Colorectal Cancer) and Petaling district (Breast Cancer)
      respectively, in the form of a pre-post randomly selected household survey and
      collection of service utilisation data. Occupants who are aged 40-years and above
      and are able to answer questions independently will be selected from each
      household. A sample of 730 with 80% power will detect a change of 6.09% in
      knowledge that unexplained lump or swelling is a symptom of breast cancer or
      changes in bowel habits is a symptom of colorectal cancer. DISCUSSION: Malaysia
      and most South-East Asian countries have a low middle-income economy, with
      limited resources for cancer control. Late-staged cancers impose a significant
      economic burden on patients, households, communities, employers, health systems
      and governments. Our proposed strategy for the implementation of the culturally
      sensitive mass media cancer awareness-raising campaign will serve as a blueprint
      for cancer prevention and control policy in South-East Asian countries where the
      burden of cancer is increasing and there are high cancer death rates.

PMID- 30200905
TI  - Which user errors matter during HIV self-testing? A qualitative participant
      observation study of men who have sex with men (MSM) in China.
AB  - BACKGROUND: The World Health Organization recommends HIV self-testing (HIVST) as
      an additional approach to HIV testing services. We aimed to assess to what extent
      HIVST was conducted correctly by Chinese men who have sex with men (MSM) and to
      identify user errors during the HIVST process in order to inform strategies to
      optimize its use and thus reduce the number of undiagnosed HIV infections.
      METHODS: Between February and March 2017, participant observations were conducted
      with 27 MSM in an east coastal city in China. In the presence, but without the
      assistance or orientation, of a trained HIV testing counselor, participants
      conducted HIVST (either finger prick or oral fluid) according to manufacturers'
      instructions. Errors were recorded on checklists during direct observation and
      double checked afterwards by reviewing video files of the observations. RESULTS:
      Overall, 12 participants (44.4%) had invalid test results due to user errors.
      Just five (18.5%) did not make any errors during the entire HIVST process.
      Failure to follow all the steps based on manufactures' instructions was a common
      problem for both finger prick and oral fluid self-testers. For finger prick
      users, most errors occurred during the stage of collecting the specimen. In
      contrast, oral fluid users made most errors during the stage of testing the
      collected specimen. CONCLUSIONS: Although we found that user errors were common
      among MSM administering HIVST, this should not deter or discourage routine
      implementation and scale-up of HIVST as strategies can be implemented to
      facilitate the correct use of HIVST. TRIAL REGISTRATION: This study was a part of
      a clinical trial: ClinicalTrials.gov (# NCT02999243 ); Registration date:
      December 20, 2016.

PMID- 30200907
TI  - Progression of retinal pigmentation mimicking unilateral retinitis pigmentosa
      after bilateral pars planitis: a case report.
AB  - BACKGROUND: To report our findings in a young patient with unilateral retinitis
      pigmentosa (RP)-like appearance who developed pigmentary changes in his left
      retina after an episode of bilateral pars planitis. CASE PRESENTATION: A 17-year
      old man presented with 6 months of blurry vision in both eyes. He was diagnosed
      with bilateral pars planitis. Progressive, intraretinal bone crepuscule
      pigmentation developed in his left retina during the following three months. An
      electroretinogram showed subnormal response only in the left eye, suggesting the
      diagnosis of unilateral pseudoRP. CONCLUSION: An inflammatory disease like pars
      planitis can accelerate the pigmentation of the retina and mimic a RP in young
      patients. Causes of pseudoRP may be considered, especially in those rare cases
      with unilateral affection.

PMID- 30200906
TI  - Light therapy as a treatment of cancer-related fatigue in (non-)Hodgkin lymphoma
      survivors (SPARKLE trial): study protocol of a multicenter randomized controlled
      trial.
AB  - BACKGROUND: Cancer related fatigue (CRF) is one of the most prevalent and
      distressing long-term complaints reported by (non-) Hodgkin survivors. To date
      there has been no standard treatment for CRF in this population. A novel and
      promising approach to treat CRF is exposure to bright white light therapy. Yet,
      large scale randomized controlled trials testing its efficacy in these patients
      and research on potential mechanisms is lacking. The objective of the current
      study is to investigate the efficacy of light therapy as a treatment for CRF and
      to explore potential mechanisms. METHODS/DESIGN: In a multicenter, randomized
      controlled trial we are evaluating the efficacy of two intensities of light
      therapy in reducing CRF complaints and restrictions caused by CRF in survivors of
      Hodgkin lymphoma or diffuse large B-cell lymphoma. Secondary outcomes include
      sleep quality, depression, anxiety, quality of life, cognitive complaints, cancer
      worries, fatigue catastrophizing, self-efficacy to handle fatigue, biological
      circadian rhythms of melatonin, cortisol and activity, and biomarkers of
      inflammation. We will recruit 128 survivors, with fatigue complaints, from
      academic and general hospitals. Survivors are randomized to either an
      intervention (exposure to bright white light) or a comparison group (exposure to
      dim white light). The longitudinal design includes four measurement points at
      baseline (T0), post-intervention at 3.5 weeks (T1), 3 months post-intervention
      (T2) and 9 months post-intervention (T3). Each measurement point includes self
      reported questionnaires and actigraphy (10 days). T0 and T1 measurements also
      include collection of blood and saliva samples. DISCUSSION: Light therapy has the
      potential to be an effective treatment for CRF in cancer survivors. This study
      will provide insights on its efficacy and potential mechanisms. If proven to be
      effective, light therapy will provide an easy to deliver, low-cost and low-burden
      intervention, introducing a new era in the treatment of CRF. TRIAL REGISTRATION:
      The study is registered at ClinicalTrials.gov on August 8th 2017( NCT03242902 ).

PMID- 30200908
TI  - Playground activities and gender variation in objectively measured physical
      activity intensity in Australian primary school children: a repeated measures
      study.
AB  - BACKGROUND: Recent studies have sought to address the limited time for physical
      activity by focusing on increasing physical activity intensity among students
      during non-curricula periods and specifically school break times. We objectively
      measured the intensity of student physical activity (PA) during recess and lunch
      breaks at primary schools in the Western Sydney region of New South Wales (NSW),
      Australia using a 12-month repeated measures observation design study. METHODS:
      Systematic direct observation of recess and lunch breaks over a ten-week period
      in 2014 and 2015. 120 recess and lunch breaks across twenty schools (2014) with
      839 periodic observations and across 15 schools with 587 periodic observations in
      2015. Both observation periods were conducted over 10-weeks in Term 4 (September 
      December). RESULTS: The mean proportion of vigorous physical activity reported
      as a percentage (%VPA) across both time points was 16.6% (SD = 23.4). 36.8% (SD =
      26.0) of time was spent walking and the remaining time (46.6%; SD = 30.4) was
      spent in sedentary activities. There was a significant decline in %VPA and
      increase in sedentary activity (p < 0.01) between the two time periods of
      measurement. In 2014, boys spent twice as much time in %VPA than girls during
      breaks in the school day and in 2015 this increased to nearly three times as much
      time in %VPA. %VPA also varied on the type of surface PA took place and the types
      of activities the children were allowed to undertake during breaks. CONCLUSIONS:
      Recess and lunch breaks potentially offer an opportunity for children to
      participate in unstructured PA during the school day. Substantial variations in
      the %VPA during these periods exist. Addressing playground gender participation
      disparities and space usability/accessibility may be a necessary first step in
      promoting higher PA intensities during breaks.

PMID- 30200909
TI  - Association between dietary patterns and hypertension among Han and multi-ethnic
      population in southwest China.
AB  - BACKGROUND: Different dietary patterns and the risks of hypertension in various
      diet exposures among multi-ethnic population in southwest China remain extremely
      scarce. The aim of this study is to identify dietary patterns and explore the
      association between dietary patterns and the risk of hypertension among Han and
      multi-ethnic population in southwest China. METHODS: A representative sample of
      3591 participants of Han, and multi-ethnic population were recruited by
      stratified cluster sampling in Diqing of Yunnan Province, southwest China from
      September 2012 to January 2013. Participants who were under 18 years old or who
      could not clearly answer the questions and those who used the anti-hypertensive
      medication were excluded from this survey. All participants reported their
      dietary intakes using validated food frequency questionnaires (FFQ), and their
      blood pressures were measured by standardized procedures. Hypertension was
      defined as systolic blood pressure (SBP) >= 140 mmHg and/or diastolic blood
      pressure (DBP) >= 90 mmHg. Dietary patterns were identified by factor analysis
      with principal component. Logistic regression was used to explore the association
      between dietary patterns and hypertension. RESULTS: The overall prevalence of
      hypertension was 30.5% among Han and multi-ethnic population in Diqing, Yunnan
      Province. Three dietary patterns were identified in this study, defined as
      'Grassland healthy', 'Tuber and meat', and 'Fruit and vegetable'. Participants in
      the 5th quintile of the three dietary patterns were at a lower risk of
      hypertension compared with those in the 1st quintile. The odds ratio (OR) for the
      5th quintile of 'Grassland healthy' pattern, 'Tuber and meat' and 'Fruit and
      vegetable' was 0.693 (95% CI: 0.537-0.893, p = 0.005), 0.678 (95% CI: 0.530
      0.868, p = 0.002), 0.759 (95% CI: 0.593-0.970, p = 0.028), respectively. After
      further adjustment of participants' age, the negative association between the
      'Grassland healthy' pattern and the prevalence of hypertension persisted (OR =
      0.703, 95% CI: 0.535-0.924, p = 0.012). However, the significant associations
      between the other two dietary patterns and hypertension disappeared. CONCLUSIONS:
      The 'Grassland healthy' dietary pattern is associated with lower risk of
      hypertension, whereas there is no significant associations between the other two
      dietary patterns and hypertension among Han and multi-ethnic population in Diqing
      of Yunnan province, southwest China.

PMID- 30200911
TI  - Factors associated with treatment intensification in child and adolescent
      psychiatry: a cross-sectional study.
AB  - BACKGROUND: More knowledge about characteristics of children and adolescents who
      need intensive levels of psychiatric treatment is important to improve treatment
      approaches. These characteristics were investigated in those who need youth
      Assertive Community Treatment (youth-ACT). METHOD: A cross-sectional study among
      children/adolescents and their parents treated in either a regular outpatient
      clinic or a youth-ACT setting in a specialized mental health treatment center in
      the Netherlands. RESULTS: Child, parent and family/social context factors were
      associated with treatment intensification from regular outpatient care to youth
      ACT. The combination of the child, parent, and family/social context factors adds
      substantially to the predictive power of the model (Nagelkerke R2 increasing from
      36 to 45% for the three domains separately, to 61% when all domains are
      combined). The strongest predictors are the severity of psychiatric disorders of
      the child, parental stress, and domestic violence. CONCLUSIONS: Using a wide
      variety of variables that are potentially associated with treatment
      intensification from regular outpatient clinic to youth-ACT, we constructed a
      regression model illustrating a relatively strong relation between the predictor
      variables and the outcome (Nagelkerke R2 = 0.61), with three strong predictors,
      i.e. severity of psychiatric disorders of the child, parental stress, and
      domestic violence. This emphasizes the importance of a system-oriented approach
      with primary attention for problem solving and stress reduction within the
      system, in addition to the psychiatric treatment of the child, and possibly also
      the parents.

PMID- 30200910
TI  - CRITICS-II: a multicentre randomised phase II trial of neo-adjuvant chemotherapy
      followed by surgery versus neo-adjuvant chemotherapy and subsequent
      chemoradiotherapy followed by surgery versus neo-adjuvant chemoradiotherapy
      followed by surgery in resectable gastric cancer.
AB  - BACKGROUND: Although radical surgery remains the cornerstone of cure in
      resectable gastric cancer, survival remains poor. Current evidence-based
      (neo)adjuvant strategies have shown to improve outcome, including perioperative
      chemotherapy, postoperative chemoradiotherapy and postoperative chemotherapy.
      However, these regimens suffer from poor patient compliance, particularly in the
      postoperative phase of treatment. The CRITICS-II trial aims to optimize
      preoperative treatment by comparing three treatment regimens: (1) chemotherapy,
      (2) chemotherapy followed by chemoradiotherapy and (3) chemoradiotherapy.
      METHODS: In this multicentre phase II non-comparative study, patients with
      clinical stage IB-IIIC (TNM 8th edition) resectable gastric adenocarcinoma are
      randomised between: (1) 4 cycles of docetaxel+oxaliplatin+capecitabine (DOC), (2)
      2 cycles of DOC followed by chemoradiotherapy (45Gy in combination with weekly
      paclitaxel and carboplatin) or (3) chemoradiotherapy. Primary endpoint is event
      free survival, 1 year after randomisation (events are local and/or regional
      recurrence or progression, distant recurrence, or death from any cause).
      Secondary endpoints include: toxicity, surgical outcomes, percentage radical (R0)
      resections, pathological tumour response, disease recurrence, overall survival,
      and health related quality of life. Exploratory endpoints include translational
      studies on predictive and prognostic biomarkers. DISCUSSION: The aim of this
      study is to select the most promising among three preoperative treatment arms in
      patients with resectable gastric adenocarcinoma. This treatment regimen will
      subsequently be compared with the standard therapy in a phase III trial. TRIAL
      REGISTRATION: clinicaltrials.gov NCT02931890 ; registered 13 October 2016. Date
      of first enrolment: 21 December 2017.

PMID- 30200912
TI  - What's the difference? A gender perspective on understanding educational
      inequalities in all-cause and cause-specific mortality.
AB  - BACKGROUND: Material and behavioural factors play an important role in explaining
      educational inequalities in mortality, but gender differences in these
      contributions have received little attention thus far. We examined the
      contribution of a range of possible mediators to relative educational
      inequalities in mortality for men and women separately. METHODS: Baseline data
      (1991) of men and women aged 25 to 74 years participating in the prospective
      Dutch GLOBE study were linked to almost 23 years of mortality follow-up from
      Dutch registry data (6099 men and 6935 women). Cox proportional hazard models
      were used to calculate hazard ratios with 95% confidence intervals, and to
      investigate the contribution of material (financial difficulties, housing tenure,
      health insurance), employment-related (type of employment, occupational class of
      the breadwinner), behavioural (alcohol consumption, smoking, leisure and sports
      physical activity, body mass index) and family-related factors (marital status,
      living arrangement, number of children) to educational inequalities in all-cause
      and cause-specific mortality, i.e. mortality from cancer, cardiovascular disease,
      other diseases and external causes. RESULTS: Educational gradients in mortality
      were found for both men and women. All factors together explained 62% of
      educational inequalities in mortality for lowest educated men, and 71% for lowest
      educated women. Yet, type of employment contributed substantially more to the
      explanation of educational inequalities in all-cause mortality for men (29%) than
      for women (- 7%), whereas the breadwinner's occupational class contributed more
      for women (41%) than for men (7%). Material factors and employment-related
      factors contributed more to inequalities in mortality from cardiovascular disease
      for men than for women, but they explained more of the inequalities in cancer
      mortality for women than for men. CONCLUSIONS: Gender differences in the
      contribution of employment-related factors to the explanation of educational
      inequalities in all-cause mortality were found, but not of material, behavioural
      or family-related factors. A full understanding of educational inequalities in
      mortality benefits from a gender perspective, particularly when considering
      employment-related factors.

PMID- 30200913
TI  - Nomograms for predicting risk of locoregional recurrence and distant metastases
      for esophageal cancer patients after radical esophagectomy.
AB  - BACKGROUND: The aim of this study was to develop nomograms for predicting the
      risk of locoregional recurrence or distant metastasis in esophageal cancer
      patients who were treated with esophagectomy and regional lymphadenectomy.
      METHODS: The clinicopathologic data of 408 esophageal cancer patients after
      esophagectomy and regional lymphadenectomy were analyzed in this study.
      Univariate and multivariate COX regression analyses were used to test the
      association between the clinicopathologic data and the risk of locoregional
      recurrence or distant metastasis. The nomograms were built from the COX
      regression model. RESULTS: Univariate analyses revealed that tumor length, tumor
      width, T-staging and perineural invasion(PNI) were significantly associated with
      locoregional recurrence, and that tumor length, tumor width, differentiation, T
      staging, N-staging, lymph vascular space invasion(LVSI), PNI and adjuvant
      chemotherapy were significantly associated with distant metastasis. Multivariate
      analyses revealed that tumor length, tumor width and T-staging were predictors of
      risk of locoregional recurrence, and that differentiation, N-staging, LVSI and
      PNI were predictors of risk of distant metastasis. Two nomograms were constructed
      for a visual explanation of these two COX regression models. The bias-corrected
      curve showed no significant departure from the ideal curve in these two
      nomograms. CONCLUSIONS: Two nomograms were developed and validated to predict the
      risk of locoregional recurrence and distant metastasis in esophageal cancer
      patients after radical esophagectomy. The calculation outcome will help
      oncologists to choose adjuvant treatment regimens.

PMID- 30200914
TI  - Retrospective analysis of risk factors and gaps in prevention strategies for
      mother-to-child HIV transmission in Rio de Janeiro, Brazil.
AB  - BACKGROUND: Despite great progress made in methods to prevent mother-to-child
      transmission of HIV (MTCT), delivery and uptake of these measures remains a
      challenge in many countries. Although the Brazilian Ministry of Health aimed to
      eliminate MTCT by 2015, infection still occured in 15-24% of infants born to HIV
      infected mothers. We sought to identify remaining factors that constrain MTCT
      elimination. METHODS: We conducted a retrospective, matched case-control study by
      reviewing hospital charts of infants born to HIV-infected mothers between 1997
      and 2014 at three MTCT reference hospitals in the Rio de Janeiro metropolitan
      area. Cases were defined as HIV-exposed children with two positive HIV tests
      before 18 months of age; controls were defined as HIV-exposed children with two
      negative HIV tests before 18 months of age. We performed bivariate and MTCT
      cascade analyses to identify risk factors for MTCT and gaps in prevention
      services. RESULTS: We included 435 infants and their mothers (145 cases, 290
      controls). Bivariate analyses of MTCT preventative care (PMTCT) indicated that
      cases were less likely to complete all individual measures in the antenatal,
      delivery, and postnatal period (p < 0.05). Assessing completion of the PMTCT
      cascade, the sequential steps of PMTCT interventions, we found inadequate
      retention in care among both cases and controls, and cases were significantly
      less likely than controls to continue receiving care throughout the cascade (p <
      0.05). Motives for incompletion of PMTCT measures included infrastructural
      issues, such as HIV test results not being returned, but were most often due to
      lack of care-seeking. Over the course of the study period, PMTCT completion
      improved, although it remained below the 95% target for antenatal care, HIV
      testing, and antenatal ART set by the WHO. Adding concern, evaluation of co
      infections indicated that case infants were also more likely to have congenital
      syphilis (OR: 4.29; 95% CI: 1.66 to 11.11). CONCLUSIONS: While PMTCT coverage has
      improved over the years, completion of services remains insufficient. Along with
      interventions to promote care-seeking behaviour, increased infrastructural
      support for PMTCT services is needed to meet the HIV MTCT elimination goal in
      Brazil as well as address rising national rates of congenital syphilis.

PMID- 30200915
TI  - Correction to: Observational study on the prognostic value of testosterone and
      adiposity in postmenopausal estrogen receptor positive breast cancer patients.
AB  - Following publication of the original article [1], the authors reported that the
      affiliation of author Annalisa Orenti was omitted.

PMID- 30200916
TI  - Evaluation of neonatal and maternal morbidity in mothers with gestational
      diabetes: a population-based study.
AB  - BACKGROUND: Gestational diabetes mellitus (GDM) is the most frequent complication
      during pregnancy. Untreated GDM is a severe threat to maternal and neonatal
      health. Based on recent evidence, up to 15% of all pregnancies may be affected by
      GDM. We hypothesized that in a rural birth cohort, higher maternal BMI and
      adverse socioeconomic conditions would promote GDM, which in turn would lead to
      adverse effects on pregnancy outcomes. METHODS: The current study is a part of a
      population-based cohort study examining the health and socioeconomic information
      from 5801 mothers and their children. The study, titled the Survey of Neonates in
      Pomerania (SNiP), was based in northeastern Pomerania, Germany (2002-2008).
      RESULTS: The cumulative incidence of GDM was 5.1%. Multiple logistic regression
      revealed prepregnancy overweight (OR 1.84 (95% CI 1.27-2.68)), prepregnancy
      obesity (OR 3.67 (2.48-5.44)) and maternal age (OR 1.06 (1.03-1.08)) as risk
      factors for GDM (p = 0.001). Alcohol use during pregnancy (OR 0.61 (0.41-0.90), a
      higher monthly income (OR 0.62 (0.46-0.83)), and the highest level of education
      (OR 0.44 (0.46-0.83)) decreased the risk of GDM. Newborns of GDM mothers had an
      increased risk of hypoglycaemia (OR 11.71 (7.49-18.30)) or macrosomia (OR 2.43
      (1.41-4.18)) and were more often delivered by primary (OR 1.76 (1.21-2.60)) or
      secondary C-section (OR 2.00 (1.35-2.97)). Moreover, they were born 0.78 weeks
      (95% CI -1.09 - -0.48 weeks) earlier than infants of mothers without diabetes,
      resulting in higher percentage of late preterm infants with a gestational age of
      32-36 weeks (11.1% vs. 6.96%). CONCLUSIONS: Age and BMI before pregnancy were the
      predominant mediators of the increased risk of GDM, whereas a higher income and
      educational level were protective. GDM affected relevant perinatal and neonatal
      outcomes based on its association with an increased risk of delivery by C
      section, preterm birth, macrosomia at birth and neonatal hypoglycaemia.

PMID- 30200917
TI  - Solid part size is an important predictor of nodal metastasis in lung cancer with
      a subsolid tumor.
AB  - BACKGROUND: Candidates for preoperative or intraoperative nodal assessment among
      patients with non-small cell lung cancer (NSCLC) manifesting as a subsolid tumor
      are not established. The present study was conducted to demonstrate the
      distribution of nodal metastasis rate according to newly proposed T categories
      for subsolid tumors, and we further aimed to identify radiologic parameters that
      can be predictive of nodal metastasis. METHODS: We retrospectively reviewed cases
      of NSCLC manifesting as a subsolid tumor in computed tomography scans in a
      university-affiliated tertiary hospital between April 2013 and August 2016. All
      patients underwent mediastinal lymph node dissection during resection surgery.
      Multivariate analysis was performed among clinical and radiologic parameters.
      RESULTS: Of the 269 eligible patients, T-categories were classified as cTis (n =
      23, 8.6%), cT1 (n = 203, 75.5%), and cT2 (n = 43, 16.0%). Ten patients (3.7%) had
      nodal metastasis: pN1 (n = 5, 1.9%), pN2 (n = 5, 1.9%). Nodal metastasis was not
      observed in tumors with a solid part <=1.0 cm (cT1mi and cT1a) or in nonsolid
      tumors <=3.0 cm (cTis). The nodal metastasis rate in cT1b, cT1c, and cT2 tumors
      was 6.1% (4/65), 8.3% (1/12), and 11.7% (5/43), respectively. Multivariate
      analysis showed that a solid part size > 1.5 cm [odds ratio, 5.89; 95% confidence
      interval, 1.25-27.68, p = 0.025] was significantly associated with nodal
      metastasis. CONCLUSIONS: We observed nodal metastasis from cT1b tumors (solid
      part size > 1 cm) among proposed T categories for subsolid tumors and a solid
      part size is an important radiologic parameter predictive of nodal metastasis in
      NSCLC manifesting as a subsolid tumor. Considering the low rate of nodal
      metastasis, pathologic nodal assessment may be unnecessary in early T category
      tumors with a small solid part size.

PMID- 30200918
TI  - Decreased expression of BRAF-activated long non-coding RNA is associated with the
      proliferation of clear cell renal cell carcinoma.
AB  - BACKGROUND: BRAF-activated long non-coding RNA (BANCR) has been associated with
      various types of cancer. Nevertheless, the role of BANCR in clear cell renal cell
      carcinoma (ccRCC) is still not fully understood. This study aims to investigate
      the relationship between ccRCC and BANCR. METHODS: Expression of BANCR in TCGA
      renal cancer data sets was analyzed. The expression pattern of BANCR in
      Immortalized normal human proximal tubule epithelial cell line HK-2 and ccRCC
      cell lines (ACHN, CAKI-1, A498 and 786-O) was detected by real-time quantitative
      RT-PCR (qRT-PCR). ccRCC tissues with adjacent normal renal tissues diagnosed by
      pathological methods from 62 patients were used to detect the expression of
      BANCR, and its correlation with prognosis of ccRCC patients was assessed by
      Kaplan-Meier method. The LV-BANCR vector was used to examine the influence of
      BANCR on the proliferation, migration, invasion, apoptosis and cell cycle
      distribution of ccRCC cells in vitro. RESULTS: BANCR was downregulated in renal
      cancer according to TCGA data sets. Compared with adjacent normal renal tissues
      and normal human proximal tubule epithelial cell line HK-2, BANCR expression was
      significantly decreased in ccRCC tissues and ccRCC cell lines, and its low
      expression was associated with poor prognosis. Moreover, in the condition of
      BANCR overexpression by LV-BANCR vector, the proliferation, migration, invasion
      capacity of ccRCC cells was inhibited, while the apoptosis was increased and the
      G1 cell cycle arrest was induced in vitro. CONCLUSIONS: BANCR is downregulated in
      ccRCC tissues and cell lines, and is associated with ccRCC progression. Thus,
      BANCR may represent a novel prognostic biomarker and a potential therapeutic
      target for ccRCC patients.

PMID- 30200919
TI  - Development of the 'Canteen Scan': an online tool to monitor implementation of
      healthy canteen guidelines.
AB  - BACKGROUND: To improve the availability and accessibility of healthier food and
      drinks in schools, sports and worksites canteens, national Guidelines for
      Healthier Canteens were developed by the Netherlands Nutrition Centre. Until now,
      no tool was available to monitor implementation of these guidelines. This study
      developed and assessed the content validity and usability of an online tool (the
      'Canteen Scan') that provides insight into and directions for improvement of
      healthier food products in canteens. METHODS: The Canteen Scan was developed
      using a three-step iterative process. First, preliminary measures and items to
      evaluate adherence to the guidelines were developed based on literature, and on
      discussions and pre-tests with end-users and experts from science, policy and
      practice. Second, content validity of a paper version of the Canteen Scan was
      assessed among five end-users. Third, the online Canteen Scan was pilot tested
      among end-users representing school canteens. Usability was measured by
      comprehensibility, user-friendliness, feasibility, time investment, and
      satisfaction. RESULTS: The content validity of the Canteen Scan was ensured by
      reaching agreement between stakeholders representing science, policy and
      practice. The scan consists of five elements: 1) basic conditions (e.g.
      encouragement to drink water and availability of policy regarding the
      guidelines), 2) product availability offered on displays (counter, shelf) and 3)
      in vending machines, 4) product accessibility (e.g. promotion and placement of
      products), and 5) an overall score based on the former elements and tailored
      feedback for creating a healthier canteen. The scan automatically classifies
      products into healthier or less healthy products. Pilot tests indicated good
      usability of the tool, with mean scores of 4.0-4.6 (5-point Likert scale) on the
      concepts comprehensibility, user-friendliness and feasibility. CONCLUSION: The
      Canteen Scan provides insight into the extent to which canteens meet the Dutch
      Guidelines for Healthier Canteens. It also provides tailored feedback to support
      adjustments towards a healthier canteen and with the scan changes over time can
      be monitored. Pilot tests show this tool to be usable in practice.

PMID- 30200920
TI  - Does household help prevent loneliness among the elderly? An evaluation of a
      policy reform in the Netherlands.
AB  - BACKGROUND: Household help is a community intervention in the Netherlands. Its
      primary goal is to provide professional help in doing domestic work. A secondary
      goal of the intervention is to alleviate loneliness. In 2007, a major health care
      reform and budget cut changed household help. After the reform alleviating
      loneliness is no longer an aim of the intervention. In this study we evaluate the
      effects of the policy change in household help on loneliness among older adults
      in the Netherlands. METHODS: We use SHARE data collected during the period 2004
      2013 to compare levels of loneliness among older adults in the Netherlands and
      those in 9 other European countries (Austria, Belgium, Germany, Denmark, Italy,
      France, Sweden, Spain and Switzerland). We use a synthetic control method (SCM)
      based on aggregate data. To check the robustness of our results we also apply a
      difference-in-differences (DiD) estimator that allows us to estimate the effects
      of policy changes using individual level data. RESULTS: In 2004, the prevalence
      of loneliness ranged between 6.5% in the Netherlands and 15.4% in Italy.
      Loneliness increased with time for all observed countries. The increase between
      2004 and 2013 was highest in France - 30.2%, Italy - 33. 4% and Belgium - 25.0%.
      The level of loneliness among older adults in the Netherlands increased after
      2011. However, it is still lower than in other countries. There was no
      statistical significant difference in age between waves (67.36 +/- 13.7 before
      2011 to 68.55 +/- 9.24 after 2011, p = 0.01). Based on the DiD estimator, there
      is no statistically significant difference in the incidence of loneliness between
      older adults in the Netherlands and those in the control countries. CONCLUSION:
      Our results do not suggest that the policy change and budget cut in 2007 on
      household help has had an effect on loneliness. In absolute numbers, the
      prevalence of loneliness has increased since 2011, however we find no evidence
      that this can be attributed to the policy change.

PMID- 30200921
TI  - Local ablation or radioembolization of colorectal cancer metastases:
      comorbidities or older age do not affect overall survival.
AB  - BACKGROUND: Local ablative techniques are emerging in patients with
      oligometastatic disease from colorectal carcinoma, commonly described as less
      invasive than surgical methods. This single arm cohort seeks to determine whether
      such methods are suitable in patients with comorbidities or higher age. METHODS:
      Two hundred sixty-six patients received radiofrequency ablation (RFA), CT-guided
      high-dose rate brachytherapy (HDR-BT) or Y90-radioembolization (Y90-RE) during
      treatment of metastatic colorectal cancer (mCRC). This cohort comprised of
      patients with heterogenous disease stages from single liver lesions to multiple
      organ systems involvement commonly following multiple chemotherapy lines. Data
      was reviewed retrospectively for patient demographics, previous therapies,
      initial or disease stages at first intervention, comorbidities and mortality.
      Comorbidity was measured using the Charlson Comorbidity Index (CCI) and age
      adjusted Charlson Index (CACI) excluding mCRC as the index disease. Kaplan-Meier
      survival analysis and Cox regression were used for statistical analysis. RESULTS:
      Overall median survival of 266 patients was 14 months. Age >= 70 years did not
      influence survival after local therapies. Similarly, CCI or CACI did not affect
      the patients prognoses in multivariate analyses. Moderate or severe renal
      insufficiency (n = 12; p = 0.005) was the only single comorbidity identified to
      negatively affect the outcome after local therapy. CONCLUSION: Interventional
      procedures for mCRC may be performed safely even in elderly and comorbid
      patients. In severe renal insufficiency, the use of invasive techniques should be
      limited to selected cases.

PMID- 30200922
TI  - Prevalence of poppers use and its sexual risks among men who have sex with men in
      southwestern China: a cross-sectional study.
AB  - BACKGROUND: To investigate the prevalence of poppers use and its relationship
      with sexual risk behaviors among men who have sex with men (MSM) in southwestern
      China. METHODS: This cross-sectional study was conducted in three cities of
      southwestern China between July and September 2016. Anonymous questionnaire
      survey was administered to collect data on demographics, drug use, sexual
      behaviors, history of STIs and HIV infection. Logistic regression analysis was
      performed to explore factors correlated with sexual risk behaviors including
      group sex and unprotected anal intercourse (UAI). RESULTS: Of the 1122
      participants included in the study, 24.1% reported a history of poppers use.
      11.6% MSM reported ever engaging in group sex and 36.2% participants reported UAI
      with non-regular male partners in the past 12 months. Multivariate logistic
      analysis showed that age > 25 (OR = 2.96, 95% CI 1.87-4.68), seeking sex partners
      through the internet (OR = 3.16, 95% CI 1.59-6.29), preferring receptive anal
      intercourse (OR = 1.91, 95% CI 1.12-3.26) and ever using poppers (OR = 1.88, 95%
      CI 1.25-2.83) were positively associated with engaging in group sex. Lower levels
      of education (OR = 1.93, 95% CI 1.33-2.80) and ever using poppers (OR = 1.44, 95%
      CI 1.01-2.05) were significantly correlated with UAI with non-regular partners.
      CONCLUSIONS: The study suggested poppers was prevalent among MSM and its use was
      significantly associated with sexual risk behaviors. Given high prevalence of HIV
      among this subpopulation, comprehensive measures are needed to decrease poppers
      use and its potential risk for HIV transmission in southwestern China.

PMID- 30200923
TI  - A thematic analysis assessing clinical decision-making in antipsychotic
      prescribing for schizophrenia.
AB  - BACKGROUND: In recent decades atypical antipsychotics have increased treatment
      options available for schizophrenia, however there is conflicting evidence
      concerning the trade-off between clinical efficacy and side effects for the
      different classes of antipsychotics. There has been a consistent increase in
      atypical antipsychotic prescribing compared to typical, despite evidence showing
      that neither class is superior. This leads to the question of whether prescribers
      are selective in their uptake of research evidence and clinical guidelines and if
      so, what influences their choice.. This study aims to identify the factors that
      contribute to the prescribing choice and how these can be used to aid knowledge
      translation and guideline implementation. METHODS: A thematic analysis study was
      conducted using data from 11 semi-structured interviews with clinicians with
      experience in prescribing for schizophrenia. RESULTS: The analysis identified
      five themes underpinning prescribing behaviour: (1) ownership and collaboration;
      (2) compromise; (3) patient involvement; (4) integrating research evidence; and
      (5) experience. CONCLUSION: The themes mapped to various degrees onto current
      models of evidence-based decision making and suggest that there is scope to re
      think the guideline implementation frameworks to incorporate recurring themes
      salient to clinicians who ultimately use the guidelines. This will further
      translation of future evidence into clinical practice, accelerating clinical
      progress.

PMID- 30200924
TI  - Basal cell adenocarcinoma of the nasopharyngeal minor salivary glands: a case
      report and review of the literature.
AB  - BACKGROUND: Basal cell adenocarcinomas (BCACs) arise from the minor salivary
      glands in the upper respiratory tract and are extremely rare. In this report, we
      present an unusual case of a 57-year-old male with BCAC that arose from the
      nasopharynx. To our knowledge, this is the first case report of nasopharyngeal
      BCAC. CASE PRESENTATION: In August 2010, a 57-year-old Chinese male presented
      with epistaxis and decreased hearing for 1 month. He was diagnosed with BCAC of
      the solid type that arose from the nasopharynx. The patient received radiotherapy
      alone and exhibited a complete response. A follow-up at 72 months did not detect
      any evidence of disease recurrence or metastasis. A comprehensive literature
      review revealed only 7 previously reported cases of BCAC in the upper respiratory
      tract. Surgery is the first choice to treat BCAC but may impair maxillofacial
      function. Radiotherapy is reserved for inoperable cases. CONCLUSIONS:
      Radiotherapy can achieve good local control and preserve maxillofacial function;
      therefore, this treatment may be a suitable option for patients who are not good
      candidates for surgery.

PMID- 30200925
TI  - Benefits for African American and white low-income 7-10-year-old children and
      their parents taught together in a community-based weight management program in
      the rural southeastern United States.
AB  - BACKGROUND: Low-income children and parents are at increased risk for developing
      overweight and obesity. Therefore, the purpose of this exploratory study was to
      compare whether African American and white children and parents benefitted
      equally from a community-based weight management intervention delivered in two
      rural counties in southeastern North Carolina (N.C.). METHODS: We compared the
      efficacy of the Family Partners for Health intervention for African American and
      white children and their parents by testing the three-way interaction of the
      intervention group according to visit and race. RESULTS: African American
      children in the intervention group weighed significantly (P = 0.027) less than
      those in the control group, while white children in the intervention group
      weighed less than those in the control group, but the difference did not reach
      statistical significance. African American and white parents in the intervention
      group weighed less than their respective control groups across all three data
      collections, but the difference was only significant in the group of white
      parents (P = 0.010) at the completion of the study. At the completion of the
      study, African American children in the intervention group received significantly
      (P = 0.003) more support for physical activity than African American children in
      the control group. At both time points, white children in the intervention group
      were not significantly different from those in the control group. African
      American parents in the intervention group scored slightly worse in the stress
      management assessment compared to those in the control group, while white parents
      in the intervention group showed a significantly (P = 0.041) better level of
      stress management than those in the control group. At the completion of the
      study, African American parents in the intervention group scored somewhat worse
      in emotional eating self-efficacy compared to the scores of the African American
      parents in the control group, while white parents in the intervention group
      scored significantly (P < 0.001) better than those in the control group.
      CONCLUSIONS: We were successful in affecting some outcomes in both African
      American and white children and parents using the same intervention. TRIAL
      REGISTRATION: NCT01378806 Registered June 22, 2011.

PMID- 30200926
TI  - Programme choice for perimetry in neurological conditions (PoPiN): a systematic
      review of perimetry options and patterns of visual field loss.
AB  - BACKGROUND: Visual field loss occurs frequently in neurological conditions and
      perimetry is commonly requested for patients with suspected or known conditions.
      There are currently no guidelines for how visual fields in neurological
      conditions should be assessed. There is a wide range of visual field programs
      available and the wrong choice of program can potentially fail to detect visual
      field loss. We report the results of a systematic review of the existing evidence
      base for the patterns of visual field loss in four common neurological conditions
      and the perimetry programs used, to aid the design of future research and
      clinical practice guidelines. METHODS: A systematic search of the literature was
      performed. The inclusion criteria required studies testing and/or reporting
      visual field loss in one or more of the target conditions; idiopathic
      intracranial hypertension, optic neuropathy, chiasmal compression and stroke.
      Scholarly online databases and registers were searched. In addition articles were
      hand searched. MESH terms and alternatives in relation to the four target
      conditions and visual fields were used. Study selection was performed by two
      authors independently. Data was extracted by one author and verified by a second.
      RESULTS: This review included 330 studies; 51 in relation to idiopathic
      intracranial hypertension, 144 in relation to optic neuropathy, 105 in relation
      to chiasmal compression, 21 in relation to stroke and 10 in relation to a mixed
      neuro-ophthalmology population. CONCLUSIONS: Both the 30-2 and 24-2 program using
      the Humphrey perimeter were most commonly reported followed by manual kinetic
      perimetry using the Goldmann perimeter across all four conditions included in
      this review. A wide variety of other perimeters and programs were reported. The
      patterns of visual field defects differ much more greatly across the four
      conditions. Central perimetry is used extensively in neurological conditions but
      with little supporting evidence for its diagnostic accuracy in these, especially
      considering the peripheral visual field may be affected first whilst the central
      visual field may not be impacted until later in the progression. Further research
      is required to reach a consensus on how best to standardise perimetry for
      neurological conditions.

PMID- 30200927
TI  - Changes in corneal endothelial cells after trabeculectomy and EX-PRESS shunt: 2
      year follow-up.
AB  - BACKGROUND: To compare trabeculectomy and EX-PRESS device implantation procedures
      for treating glaucoma and evaluate changes in corneal endothelial cell density
      (CECD). METHODS: This study prospectively evaluated changes in the CECD in 60
      eyes of 60 patients who underwent trabeculectomy and 50 eyes of 45 patients who
      underwent EX-PRESS device implantation. Baseline patient data recorded included
      age at surgery, sex, type of glaucoma medications, and lens status. Using a
      noncontact specular microscope, corneal specular microscopy was performed
      preoperatively at the central cornea and then at 6, 12, 18 and 24 months after
      surgery. CECD before and after surgery was compared using a paired t-test.
      RESULTS: There was a significant decrease in the IOP and number of antiglaucoma
      medications in both groups after the surgery. The mean CECD in the trabeculectomy
      group was 2505 +/- 280 cells/mm2 at baseline, while it was 2398 +/- 274 cells/mm2
      (P < 0.001), 2349 +/- 323 cells/mm2 (P < 0.001), 2293 +/- 325 cells/mm2 (P <
      0.001), and 2277 +/- 385 cells/mm2 (P = 0.003) at 6, 12, 18, and 24 months,
      respectively. However, the CECD in the EX-PRESS group was 2377 +/- 389 cells/mm2
      at baseline, while it was 2267 +/- 409 cells/mm2 (P = 0.007), 2292 +/- 452
      cells/mm2 (P = 0.043), 2379 +/- 375 cells/mm2 (P = 0.318), and 2317 +/- 449
      cells/mm2 (P = 0.274) at 6, 12, 18, and 24 months, respectively. CONCLUSIONS: As
      compared to trabeculectomy, EX-PRESS device implantation appears to be a safer
      procedure with regard to the endothelial cell loss risk.

PMID- 30200928
TI  - Efficacy of a mobile phone-based life-skills training program for substance use
      prevention among adolescents: study protocol of a cluster-randomised controlled
      trial.
AB  - BACKGROUND: Life-skills trainings conducted within the school curriculum are
      effective in preventing the onset and escalation of substance use among
      adolescents. However, their dissemination is impeded due to their large resource
      requirements. Life-skills training provided via mobile phones might represent a
      more economic and scalable approach. The main objective of the planned study is
      to test the efficacy of a mobile phone-based life-skills training to prevent
      substance use among adolescents within a controlled trial. METHODS/DESIGN: The
      efficacy of a mobile phone-based life-skills training to prevent substance use
      among adolescents will be tested in comparison to an assessment only control
      group, within a cluster-randomised controlled trial with two follow-up
      assessments after 6 and 18 months. The fully automated program is based on social
      cognitive theory and addresses self-management skills, social skills, and
      substance use resistance skills. Participants of the intervention group will
      receive up to 4 weekly text messages over 6 months in order to stimulate (1)
      positive outcome expectations, e.g., on using self-management skills to cope with
      stress, (2) self-efficacy, e.g., to resist social pressure, (3) observational
      learning, e.g. of interpersonal competences, (4) facilitation, e.g., of
      strategies to cope with negative emotions, and (5) self-regulation, e.g., by self
      monitoring of stress and emotions. Active program engagement will be stimulated
      by interactive features such as quiz questions, message- and picture-contests,
      and integration of a friendly competition with prizes in which program users
      collect credits with each interaction. Study participants will be 1312 students
      between the ages of 14 and 16 years from approximately 100 secondary school
      classes. Primary outcome criteria will be problem drinking according to the short
      form of the Alcohol Use Disorders Identification Test and cigarette smoking
      within the last 30 days preceding the follow-up assessment at month 18.
      DISCUSSION: This is the first study testing the efficacy of a mobile phone-based
      life-skills training for substance use prevention among adolescents within a
      controlled trial. Given that this intervention approach proves to be effective,
      it could be easily implemented in various settings and would reach large numbers
      of young people in a cost-effective way. TRIAL REGISTRATION: ISRCTN41347061
      (registration date: 21/07/2018).

PMID- 30200929
TI  - The Terry Fox Research Institute Canadian Prostate Cancer Biomarker Network: an
      analysis of a pan-Canadian multi-center cohort for biomarker validation.
AB  - BACKGROUND: Refinement of parameters defining prostate cancer (PC) prognosis are
      urgently needed to identify patients with indolent versus aggressive disease. The
      Canadian Prostate Cancer Biomaker Network (CPCBN) consists of researchers from
      four Canadian provinces to create a validation cohort to address issues dealing
      with PC diagnosis and management. METHODS: A total of 1512 radical prostatectomy
      (RP) specimens from five different biorepositories affiliated with teaching
      hospitals were selected to constitute the cohort. Tumoral and adjacent benign
      tissues were arrayed on tissue microarrays (TMAs). A patient clinical database
      was developed and includes data on diagnosis, treatment and clinical outcome.
      RESULTS: Mean age at diagnosis of patients in the cohort was 61 years. Of these
      patients, 31% had a low grade (<=6) Gleason score (GS), 55% had GS 7 (40% of 3 +
      4 and 15% of 4 + 3) and 14% had high GS (>=8) PC. The median follow-up of the
      cohort was 113 months. A total of 34% had a biochemical relapse, 4% developed
      bone metastasis and 3% of patients died from PC while 9% died of other causes.
      Pathological review of the TMAs confirmed the presence of tumor and benign tissue
      cores for > 94% of patients. Immunohistochemistry and FISH analyses, performed on
      a small set of specimens, showed high quality results and no biorepository
      specific bias. CONCLUSIONS: The CPCBN RP cohort is representative of real world
      PC disease observed in the Canadian population. The frequency of biochemical
      relapse and bone metastasis as events allows for a precise assessment of the
      prognostic value of biomarkers. This resource is available, in a step-wise
      manner, for researchers who intend to validate prognostic biomarkers in PC.
      Combining multiple biomarkers with clinical and pathologic parameters that are
      predictive of outcome will aid in clinical decision-making for patients treated
      for PC.

PMID- 30200930
TI  - Synchronous anal canal carcinoma in a heterosexual couple.
AB  - BACKGROUND: Sexually transmitted Human Papilloma Virus (HPV) infection is a known
      risk factor for cancer of the anal canal in both men and women. CASE
      PRESENTATION: We describe a report of synchronous carcinoma of the anal canal in
      a heterosexual couple. High risk type 16 HPV DNA was detected in both tumors.
      CONCLUSION: Longstanding sexual partners may share risk of HPV-associated anal
      canal cancer.

PMID- 30200931
TI  - Periprosthetic tibial fractures in total knee arthroplasty - an outcome analysis
      of a challenging and underreported surgical issue.
AB  - BACKGROUND: Periprosthetic fractures after total knee arthroplasty (TKA) are an
      increasing problem and challenging to treat. The tibial side is commonly less
      affected than the femoral side wherefore few studies and case reports are
      available. The aim of this study was to analyze the outcome of periprosthetic
      tibial fractures and compare our data with current literature. METHODS: All
      periprosthetic tibial TKA fractures that were treated at our Level 1 Trauma
      Center between 2011 and 2015 were included and analyzed consecutively. The Felix
      classification was used to assess the fracture type and evaluation included the
      radiological and clinical outcome (Knee Society Score/KSS, Oxford Knee
      Score/OKS). RESULTS: From a total of 50 periprosthetic TKA fractures, 9 cases (7
      female, 2 male; 2 cruciate retaining, 7 constrained TKAs) involving the tibial
      side were identified. The mean age in this group was 77 (65-85) years with a
      follow-up rate of 67% after a mean of 22 (0-36) months. The Felix classification
      showed type IB (n = 1), type IIB (n = 2), type IIIA (n = 4) and type IIIB (n = 2)
      and surgical intervention included ORIF (n = 6), revision arthroplasty (n = 1),
      arthrodesis (n = 1) and amputation (n = 1). The rate of adverse events and
      revision was 55.6% including impaired wound healing, infection and re-fracture
      respectively peri-implant fracture. Main revision surgery included soft tissue
      surgery, arthrodesis, amputation and re-osteosynthesis. The clinical outcome
      showed a mean OKS of 29 (19-39) points and a functional/knee KSS of 53 (40-70)/41
      (17-72) points. Radiological analyses showed 4 cases of malalignment after
      reduction and plate fixation. CONCLUSIONS: Periprosthetic tibial fractures
      predominantly affect elderly patients with a reduced bone quality and reveal a
      high complication rate. Careful operative planning with individual solutions
      respecting the individual patient condition is crucial. If ORIF with a plate is
      considered, restoration of the correct alignment and careful soft tissue
      management including minimal invasive procedures seem important factors for the
      postoperative outcome.

PMID- 30200932
TI  - Could local surgery improve survival in de novo stage IV breast cancer?
AB  - BACKGROUND: Resection of the primary tumor is recommended for symptom relief in
      de novo stage IV breast cancer. We explored whether local surgery could provide a
      survival benefit in these patients and attempted to characterize the population
      that could benefit from surgery. METHODS: Metastatic Breast cancer patients (N =
      313) with intact primary tumor between January 2006 and April 2013 were separated
      into two groups according to whether or not they had undergone surgery. The
      difference in characteristics between the two groups was analyzed using chi
      square test, Fisher's exact test and Mann-Whitney test. Univariable and
      multivariable Cox regression and stratified survival analysis were used to assess
      the effect of surgery on survival. RESULTS: Of the 313 patients, 188 (60.1%)
      underwent local surgery. Patients with local surgery had a 47% reduction in
      mortality risk vs. those with no surgery (median survival 78 months vs. 37
      months; HR = 0.53; 95% CI, 0.36-0.78) after adjustment for clinical and tumor
      characteristics. Stratified survival analysis showed that patients with bone
      metastasis alone (and primary tumor <=5 cm), soft tissue metastasis, or <= 3
      metastasis sites benefit from surgery. CONCLUSION: Surgical resection of the
      primary tumor can improve survival in selected de novo stage IV breast cancer
      patients.

PMID- 30200933
TI  - Reported incidence and risk factors of childhood pneumonia in India: a community
      based cross-sectional study.
AB  - BACKGROUND: Pneumonia is responsible for high morbidity and mortality amongst
      children under five year of age. India accounts for one-third of the total WHO
      South East Asia burden of under-five mortality. There is a paucity of
      epidemiological studies indicating the true burden of pneumonia. Identification
      of the risk factors associated with pneumonia will help to effectively plan and
      implement the preventive measures for its reduction. METHODS: It was a
      descriptive cross-sectional study conducted in 16 randomly selected clusters in
      two districts of Maharashtra state, India. All mothers of under-five children in
      the selected clusters were included. A validated pretested interview schedule was
      filled by trained field supervisors through the house to house visits.WHO
      definition was used to define and classify clinical pneumonia. Height and weight
      of children were taken as per standard guidelines. Quality checks for data
      collection were done by the site investigators and critical and noncritical
      fields in the questionnaire were monitored during data entry. For continuous
      variables mean and SD were calculated. Chi-square test was applied to determine
      the association between the variables. Level of significance was considered at
      0.05. RESULTS: There were 3671 under five-year children, 2929 mothers in 10,929
      households.Unclean fuel usage was found in 15.1% of households. Mean birth weight
      was 2.6 kg (SD;0.61). Exclusive breastfeeding till 6 months of age was practiced
      by 46% of mothers. Reported incidence of ARI was 0.49 per child per month and the
      reported incidence of pneumonia was 0.075 per child per year. It was not
      associated with any of the housing environment factors (p > 0.05) but was found
      to be associated with partial immunization (p < 0.05). Poor practices related to
      child feeding, hand hygiene and poor knowledge related to signs and symptoms of
      pneumonia amongst mother were found. CONCLUSIONS: Very low incidence of pneumonia
      was observed in Pune and Sangli districts of Maharashtra. Partial immunization
      emerged as a most important risk factor. Reasons for low incidence and lack of
      association of pneumonia with known risk factors may be a better literacy rate
      among mothers and better immunization coverage. TRIAL REGISTRATION: Registration
      number of the trial- CTRI/2017/12/010881 ; date of registration-14/12/2017.

PMID- 30200934
TI  - Benefits and limitations of three-dimensional printing technology for ecological
      research.
AB  - BACKGROUND: Ecological research often involves sampling and manipulating non
      model organisms that reside in heterogeneous environments. As such, ecologists
      often adapt techniques and ideas from industry and other scientific fields to
      design and build equipment, tools, and experimental contraptions custom-made for
      the ecological systems under study. Three-dimensional (3D) printing provides a
      way to rapidly produce identical and novel objects that could be used in
      ecological studies, yet ecologists have been slow to adopt this new technology.
      Here, we provide ecologists with an introduction to 3D printing. RESULTS: First,
      we give an overview of the ecological research areas in which 3D printing is
      predicted to be the most impactful and review current studies that have already
      used 3D printed objects. We then outline a methodological workflow for
      integrating 3D printing into an ecological research program and give a detailed
      example of a successful implementation of our 3D printing workflow for 3D printed
      models of the brown anole, Anolis sagrei, for a field predation study. After
      testing two print media in the field, we show that the models printed from the
      less expensive and more sustainable material (blend of 70% plastic and 30%
      recycled wood fiber) were just as durable and had equal predator attack rates as
      the more expensive material (100% virgin plastic). CONCLUSIONS: Overall, 3D
      printing can provide time and cost savings to ecologists, and with recent
      advances in less toxic, biodegradable, and recyclable print materials, ecologists
      can choose to minimize social and environmental impacts associated with 3D
      printing. The main hurdles for implementing 3D printing-availability of resources
      like printers, scanners, and software, as well as reaching proficiency in using
      3D image software-may be easier to overcome at institutions with digital imaging
      centers run by knowledgeable staff. As with any new technology, the benefits of
      3D printing are specific to a particular project, and ecologists must consider
      the investments of developing usable 3D materials for research versus other
      methods of generating those materials.

PMID- 30200935
TI  - Protocol for a clinical trial of text messaging in addition to standard care
      versus standard care alone in prevention of type 2 diabetes through lifestyle
      modification in India and the UK.
AB  - BACKGROUND: Type 2 diabetes is a serious clinical problem in both India and the
      UK. Adoption of a healthy lifestyle through dietary and physical activity
      modification can help prevent type 2 diabetes. However, implementing lifestyle
      modification programmes to high risk groups is expensive and alternative cheaper
      methods are needed. We are using a short messaging service (SMS) programme in our
      study as a tool to provide healthy lifestyle advice and an aid to motivation. The
      aim of the study is to assess the efficacy and user acceptability of text
      messaging employed in this way for people with pre-diabetes (HbA1c 6.0% to
      <=6.4%; 42-47 mmol/mol) in the UK and India. METHODS/DESIGN: This is a
      randomised, controlled trial with participants followed up for 2 years. After
      being screened and receiving a structured education programme for prediabetes,
      participants are randomised to a control or intervention group. In the
      intervention group, text messages are delivered 2-3 times weekly and contain
      educational, motivational and supportive content on diet, physical activity,
      lifestyle and smoking. The control group undergoes monitoring only. In India, the
      trial involves 5 visits after screening (0, 6, 12, 18 and 24 months). In the UK
      there are 4 visits after screening (0, 6, 12 and 24 months). Questionnaires (EQ
      5D, RPAQ, Transtheoretical Model of Behavioural Change, and food frequency
      (UK)/24 h dietary recall (India)) and physical activity monitors (Actigraph GT3X+
      accelerometers) are assessed at baseline and all follow-up visits. The SMS
      acceptability questionnaires are evaluated in all follow-up visits. The primary
      outcome is progression to type 2 diabetes as defined by an HbA1c of 6.5% or
      over(India) and by any WHO criterion(UK). Secondary outcomes are the changes in
      body weight, body mass index, waist circumference, blood pressure, fasting plasma
      glucose; lipids; proportion of participants achieving HbA1c <=6.0%; HOMA-IR; HOMA
      beta; acceptability of SMS; dietary parameters; physical activity and quality of
      life. DISCUSSION: The study is designed to assess the efficacy of tailored text
      messaging in addition to standard lifestyle advice to reduce the progression from
      prediabetes to type 2 diabetes in the two different countries. TRIAL
      REGISTRATION: ClinicalTrials.gov ; NCT01570946 , 4th April 2012 (India);
      NCT01795833 , 21st February 2013 (UK).

PMID- 30200936
TI  - A random survival forest illustrates the importance of natural enemies compared
      to host plant quality on leaf beetle survival rates.
AB  - BACKGROUND: Wetlands are habitats where variation in soil moisture content and
      associated environmental conditions can strongly affect the survival of
      herbivorous insects by changing host plant quality and natural enemy densities.
      In this study, we combined natural enemy exclusion experiments with random
      survival forest analyses to study the importance of local variation in host plant
      quality and predation by natural enemies on the egg and larval survival of the
      leaf beetle Galerucella sagittariae along a soil moisture gradient. RESULTS: Our
      results showed that the exclusion of natural enemies substantially increased the
      survival probability of G. sagittariae eggs and larvae. Interestingly, the egg
      survival probability decreased with soil moisture content, while the larval
      survival probability instead increased with soil moisture content. For both the
      egg and larval survival, we found that host plant height, the number of eggs or
      larvae, and vegetation height explained more of the variation than the soil
      moisture gradient by itself. Moreover, host plant quality related variables, such
      as leaf nitrogen, carbon and phosphorus content did not influence the survival of
      G. sagittariae eggs and larvae. CONCLUSION: Our results suggest that the soil
      moisture content is not an overarching factor that determines the interplay
      between factors related to host plant quality and factors relating to natural
      enemies on the survival of G. sagittariae in different microhabitats. Moreover,
      the natural enemy exclusion experiments and the random survival forest analysis
      suggest that natural enemies have a stronger indirect impact on the survival of
      G. sagittariae offspring than host plant quality.

PMID- 30200937
TI  - Esophageal groove dysfunction: a cause of ruminal bloat in newborn calves.
AB  - BACKGROUND: Esophageal groove dysfunction is one of the major causes of ruminal
      bloat. This condition is fatal in new born calves if it is not treated early. In
      healthy, suckling calves, milk should bypass the forestomach (rumen and
      reticulum) and enter into the abomasum where enzymatic digestion of milk proteins
      takes place. However, failure of the esophageal groove allows milk to enter into
      the forestomach, which results in the production of excess gases by microbial
      fermentation. Consequently, this increase in abdominal distention particularly on
      the left side in ruminants is an imminent manifestation of excess gases in the
      foresomach. CASE PRESENTATION: A 10-day-old crossbred male calf presented with a
      distended left abdomen and manifesting dyspnea at a dairy farm. The calf was
      weak, reluctant to move, and had visibly congested mucus membranes. Regarding the
      calf's feeding, milk was the only thing ingested and the calf had not started on
      dry feeds (hay, concentrates, and roughages). According to the herdsman of the
      farm, the calf had a mild-to-moderate form of bloat and 3-5 h after milk feeding
      the bloat would disappear spontaneously. During bloat, an increase in pulse rate,
      respiratory rate (tachypnea), and shallow breathing was noted. Physical
      examination revealed severe distention of the left side of the abdomen, and on
      percussion, accumulation of gases mixed with fluid in the left abdomen was
      detected. An attempt was made to release gases from forestomach by introducing a
      stomach tube with oral antibiotics; however, the case was not resolved. The calf
      suffered from frequent recurrence of bloat after every milk feed, and in response
      to the refractory outcome to conventional treatment, a rumenostomy was indicated
      and a better treatment response was achieved. In addition, IV fluid and other
      supportive therapy were provided while milk was withheld. However, considering
      the fact that milk is a natural feed that should not be taken away from every
      calf at this age, we had to encourage calf to consume milk as it would not result
      in bloat as far as rumen fistula is being created. Furthermore, encouraging
      calves to consume starter feed (fresh grasses and hay) earlier than usual
      recommended period whilst decreasing milk intake would hasten the rumen function.
      CONCLUSIONS: Cases like this are successfully managed by a rumenostomy when
      conventional options fail.

PMID- 30200938
TI  - Real-time location system-based asset tracking in the healthcare field: lessons
      learned from a feasibility study.
AB  - BACKGROUND: Numerous hospitals and organizations have recently endeavored to
      study the effects of real-time location systems. However, their experiences of
      system adoption or pilot testing via implementation were not shared with others
      or evaluated in a real environment. Therefore, we aimed to share our experiences
      and insight regarding a real-time location system, obtained via the
      implementation and operation of a real-time asset tracking system based on
      Bluetooth Low Energy/WiFi in a tertiary care hospital, which can be used to
      improve hospital efficiency and nursing workflow. METHODS: We developed tags that
      were attached to relevant assets paired with Bluetooth Low Energy sensor beacons,
      which served as the basis of the asset tracking system. Problems with the system
      were identified during implementation and operation, and the feasibility of
      introducing the system was evaluated via a satisfaction survey completed by end
      users after 3 months of use. RESULTS: The results showed that 117 nurses who had
      used the asset tracking system for 3 months were moderately satisfied (2.7 to 3.4
      out of 5) with the system, rated it as helpful, and were willing to continue
      using it. In addition, we identified 4 factors (end users, target assets,
      tracking area, and type of sensor) that should be considered in the development
      of asset tracking systems, and 4 issues pertaining to usability (the active tag
      design, technical limitations, solution functions, and operational support).
      CONCLUSIONS: The successful introduction of asset tracking systems based on real
      time location in hospitals requires the selection of clear targets (e.g., users
      and assets) via analysis of the user environment and implementation of
      appropriate technical improvements in the system as required (e.g.,
      miniaturization of the tag size and improvement of the sensing accuracy).

PMID- 30200939
TI  - User-centered design and usability testing of RxMAGIC: a prescription management
      and general inventory control system for free clinic dispensaries.
AB  - BACKGROUND: To address challenges related to medication management in underserved
      settings, we developed a system for Prescription Management And General Inventory
      Control, or RxMAGIC, in collaboration with the Birmingham Free Clinic in
      Pittsburgh, Pennsylvania. RxMAGIC is an interoperable, web-based medication
      management system designed to standardize and streamline the dispensing practice
      and improve inventory control in a free clinic setting. This manuscript describes
      the processes used to design, develop, and deploy RxMAGIC. METHODS: We
      transformed data from previously performed mixed-methods needs assessment studies
      into functional user requirements using agile development methods. Requirements
      took the form of user stories that were prioritized to drive implementation of
      RxMAGIC as a web-application. A functional prototype was developed and tested to
      understand its perceived usefulness before developing a production system. Prior
      to deployment, we evaluated the usability of RxMAGIC with six users to diagnose
      potential interaction challenges that may be avoided through redesign. The
      results from this study were similarly prioritized and informed the final
      features of the production system. RESULTS: We developed 45 user stories that
      acted as functional requirements to incrementally build RxMAGIC. Integrating with
      the electronic health record at the clinic was a requirement for deployment. We
      utilized health data standards to communicate with the existing order entry
      system; an outgoing electronic prescribing framework was leveraged to send
      prescription data to RxMAGIC. The results of the usability study were positive,
      with all tested features receiving a mean score of four or five (i.e. somewhat
      easy or easy, respectively) on a five-point Likert scale assessing ease of
      completion, thus demonstrating the system's simplicity and high learnability.
      RxMAGIC was deployed at the clinic in October 2016 over a two-week period.
      CONCLUSIONS: We built RxMAGIC, an open-source, pharmacist-facing dispensary
      management information system that augments the pharmacist's ability to
      efficiently deliver medication services in a free clinic setting. RxMAGIC
      provides electronic dispensing and automated inventory management and alerting
      capabilities. We deployed RxMAGIC at the Birmingham Free Clinic and measured its
      usability with potential users. In future work, we plan to continue to measure
      the impact of RxMAGIC on pharmacist efficiency and satisfaction.

PMID- 30200941
TI  - Does Hukou origin affect establishment of health records in migrant inflow
      communities? A nation-wide empirical study in China.
AB  - BACKGROUND: With the implementation of Chinese economic reform and rapid
      urbanization, policies and values surrounding migration have changed and given
      rise to unprecedented population mobility. This study is designed to examine the
      effect of Hukou origin on establishment of health records among internal migrants
      in China. METHODS: The data used for this study are from the 2015 National
      Internal Migrant Population Dynamic Monitoring Survey, covering 112,782 migrants
      nationwide. For continuous variables, the p value is calculated using Student t
      test; for categorical variables, the p value is calculated using chi-square test.
      Binary logistic regression with an enter method is employed to assess the
      association of establishment of health records with origin residence. RESULTS:
      About 35.1% of the migrant population has established health records in their
      inflow communities, with 37.4% established among those of urban origin and 34.8%
      established among those of rural origin. The establishment of health records is
      significantly higher among migrants of urban origin than among migrants of rural
      origin (OR = 1.057; 1.017-1.098). Our results also show that among populations of
      both rural and urban origin, inter-province migrants, along with migrants who are
      employers, have no plans for long-term residence, have no insurance, and have
      more family income less likely to establish health records. CONCLUSIONS: This
      study demonstrates that residence is associated with establishment of health
      records among the migrant population in China. Targeted policies should be made
      to improve the establishment of health records among migrants of both rural and
      urban origins.

PMID- 30200940
TI  - Parkinson's disease-linked Parkin mutations impair glutamatergic signaling in
      hippocampal neurons.
AB  - BACKGROUND: Parkinson's disease (PD)-associated E3 ubiquitin ligase Parkin is
      enriched at glutamatergic synapses, where it ubiquitinates multiple substrates,
      suggesting that its mutation/loss-of-function could contribute to the etiology of
      PD by disrupting excitatory neurotransmission. Here, we evaluate the impact of
      four common PD-associated Parkin point mutations (T240M, R275W, R334C, G430D) on
      glutamatergic synaptic function in hippocampal neurons. RESULTS: We find that
      expression of these point mutants in cultured hippocampal neurons from Parkin
      deficient and Parkin-null backgrounds alters NMDA and AMPA receptor-mediated
      currents and cell-surface levels and prevents the induction of long-term
      depression. Mechanistically, we demonstrate that Parkin regulates NMDA receptor
      trafficking through its ubiquitination of GluN1, and that all four mutants are
      impaired in this ubiquitinating activity. Furthermore, Parkin regulates synaptic
      AMPA receptor trafficking via its binding and retention of the postsynaptic
      scaffold Homer1, and all mutants are similarly impaired in this capacity.
      CONCLUSION: Our findings demonstrate that pathogenic Parkin mutations disrupt
      glutamatergic synaptic transmission in hippocampal neurons by impeding NMDA and
      AMPA receptor trafficking. Such effects may contribute to the pathophysiology of
      PD in PARK2 patients.

PMID- 30200942
TI  - Intranasal fentanyl for respiratory distress in children and adolescents with
      life-limiting conditions.
AB  - BACKGROUND: Respiratory distress is one of the most common and frightening
      symptoms of children with life-limiting conditions. Because treatment of the
      underlying cause is frequently impossible or insufficient, in many children,
      symptomatic treatment is warranted. The purpose of this study was to describe the
      circumstances of the use of intranasal fentanyl in an acute attack of respiratory
      distress (AARD) in children receiving palliative care, as well as to describe
      outcomes and adverse events after its use. METHODS: Children and adolescents
      treated in a pediatric palliative unit or attended by a specialized home care
      team between 2010 and 2016 were included in this study. A retrospective chart
      review was conducted of those who were treated with intranasal fentanyl for an
      AARD. RESULTS: During the study period 16 children (0.5-18.6 years) with various
      life-limiting conditions were treated with intranasal fentanyl for AARD. In
      total, 70 AARDs were analyzed. In 74% of all AARDs, a single dose of intranasal
      fentanyl was used. Frequent causes for an AARD were excessive secretions and
      acute respiratory infection. The median starting dose of intranasal fentanyl was
      1.5 MUg/kg body weight. Labored breathing (96%), tachypnea (79%) and related
      suffering (97%) improved after treatment. An adverse event occurred in one child.
      CONCLUSIONS: Intranasal fentanyl may be a safe and effective medication for the
      treatment of acute attacks of respiratory distress in children with life-limiting
      conditions. However, prospective studies with larger sample sizes and a control
      group are needed to validate these findings.

PMID- 30200943
TI  - The role of the assistant practitioner in the clinical setting: a focus group
      study.
AB  - BACKGROUND: Assistant practitioners have knowledge and skills beyond the level of
      traditional support workers, and work in many clinical settings. However, some
      assistant practitioners lack a clearly defined role and may be under-used due to
      issues around accountability and uncertainty about their purpose. This paper
      explores the assistant practitioner role from the perspectives of assistant
      practitioners and registered nurses. METHODS: This study aimed to explore the
      role of the assistant practitioner from the perspectives of assistant
      practitioners and registered nurses in two NHS hospital trusts in Oxfordshire,
      United Kingdom. Six qualitative focus groups were undertaken between February
      March 2017. Ethical approval was obtained (FREC 2016/05) and written consent was
      provided by participants. Data was analysed thematically analysed using the
      Framework method. RESULTS: Nineteen participants (assistant practitioners, n =
      12; registered nurses, n = 7) were recruited using convenience sampling. Emerging
      themes related to 'fluctuating roles and responsibilities of assistant
      practitioners', 'role differences between registered nurses and assistant
      practitioners', 'working relationships', 'supervision' and 'redefining nursing
      pathways'. The Results and Discussion sections highlight a lack of role clarity
      and blurring of boundaries between the roles of assistant practitioners and
      registered nurses, with many tasks undertaken by both. This lack of ownership of
      'nurse-specific' roles by registered nurses was evident and clear differences
      were only encountered with regard to accountability. The development of the
      Nursing Associate role provides managers with the opportunity to redefine staff
      banding hierarchies to ensure that clinical staff are aware of their role
      capabilities and limitations and are practicing safely, whilst promoting career
      development and progression pathways. CONCLUSION: Addressing issues around role
      clarity can benefit professional development, satisfaction, role identity and
      ownership for registered nurses and assistant practitioners, by recognising the
      individual and collective value they bring to the clinical team. The findings can
      help inform the development of the Nursing Associate role.

PMID- 30200944
TI  - The cost of Mycobacterium avium complex lung disease in Canada, France, Germany,
      and the United Kingdom: a nationally representative observational study.
AB  - BACKGROUND: Management of nontuberculous mycobacterial lung disease (NTMLD)
      consists of a long-term multi-drug antibiotic regimen, yet many patients do not
      achieve culture conversion. We estimated the NTMLD-related direct medical costs
      in Canada, France, Germany, and the United Kingdom (UK) among refractory patients
      who were infected with Mycobacterium avium complex (MAC), without concomitant
      cystic fibrosis, tuberculosis, or HIV. METHODS: We conducted a retrospective
      observational physician survey of nationally representative samples. The survey
      captured anonymized information about patients' treatment histories for NTMLD
      related health care resource utilization over a 24-month period. We summarized
      NTMLD-related resource use and estimated the total economic burden, from each
      country's health care payer perspective. RESULTS: In total, 59 physicians
      provided data on 157 patients. The average person time observed during the 24
      month period was 1.7 years (SD: 0.4); 17% of patients died by the end of the
      study period. The major components of NTMLD-related direct medical costs among
      refractory patients were hospitalizations (varying from 29% of total annual costs
      in the UK to 69% in France), outpatient visits (8% in Canada to 51% in the UK),
      and outpatient testing such as post-diagnostic sputum testing, bronchial
      wash/lavage, spirometry, biopsies, imaging, and electrocardiograms (5% in France
      to 35% in Canada). In this patient cohort, the average direct medical costs per
      person-year, in local currencies, were approximately $16,200 (Canada), ?11,600
      (Germany), ?17,900 (France) and L9,700 (UK). CONCLUSIONS: Based on this study's
      findings, we conclude that managing patients with refractory NTMLD caused by MAC
      is associated with a substantial economic burden.

PMID- 30200945
TI  - Digital storytelling in health professions education: a systematic review.
AB  - BACKGROUND: Digital stories are short videos that combine stand-alone and first
      person narratives with multimedia. This systematic review examined the contexts
      and purposes for using digital storytelling in health professions education (HPE)
      as well as its impact on health professionals' learning and behaviours. METHODS:
      We focused on the results of HPE studies gleaned from a larger systematic review
      that explored digital storytelling in healthcare and HPE. In December 2016, we
      searched MEDLINE, EMBASE, PsycINFO, CINAHL, and ERIC. We included all English
      language studies on digital storytelling that reported at least one outcome from
      Levels 2 (learning) or 3 (behaviour) of The New World Kirkpatrick Model. Two
      reviewers independently screened articles for inclusion and extracted data.
      RESULTS: The comprehensive search (i.e., digital storytelling in healthcare and
      HPE) resulted in 1486 unique titles/abstracts. Of these, 153 were eligible for
      full review and 42 pertained to HPE. Sixteen HPE articles were suitable for data
      extraction; 14 focused on health professionals' learning and two investigated
      health professionals' learning as well as their behaviour changes. Half
      represented the undergraduate nursing context. The purposes for using digital
      storytelling were eclectic. The co-creation of patients' digital stories with
      health professionals as well as the creation and use of health professionals' own
      digital stories enhanced learning. Patients' digital stories alone had minimal
      impact on health professionals' learning. CONCLUSIONS: This review highlights the
      need for high-quality research on the impact of digital storytelling in HPE,
      especially on health professionals' behaviours. PROSPERO REGISTRATION NUMBER:
      CRD42016050271 .

PMID- 30200946
TI  - Towards effective outbreak detection: a qualitative study to identify factors
      affecting nurses' early warning surveillance practice in Solomon Islands.
AB  - BACKGROUND: Intelligence generated by a surveillance system is dependent on the
      quality of data that are collected. We investigated the knowledge, attitudes and
      practices of nurses responsible for outbreak early warning surveillance data
      collection in Solomon Islands to identify factors that influence their ability to
      perform surveillance-related tasks with rigour. METHODS: We interviewed 12
      purposively selected surveillance nurses and conducted inductive analysis on
      resulting data. RESULTS: Interviewees were knowledgeable and willing to
      contribute to the surveillance system. Constraining factors included the
      perception that surveillance was less important than patient care and could be
      'deferred' during busy periods and wide variability in the application of case
      definitions. Motivating factors were frequent in-clinic training, formal
      recognition for good performance, incentives and designation of a focal point.
      Nurses held mixed views about the effect of mobile technologies on surveillance
      practice. CONCLUSIONS: This study identified several challenges to consistent and
      accurate data collection and reporting. Engagement of different parts of the
      health system, including human resources and health facilities' management, is
      needed to address these challenges.

PMID- 30200947
TI  - Coxiella and Bartonella spp. in bats (Chiroptera) captured in the Brazilian
      Atlantic Forest biome.
AB  - BACKGROUND: The role of bats as reservoirs of zoonotic agents, especially
      pathogenic bacteria such as Bartonella and Coxiella, has been discussed around
      the world. Recent studies have identified bats as potential hosts of species from
      the proteobacteria phylum. In Brazil, however, the role of bats in the natural
      cycle of these agents is poorly investigated and generally neglected. In order to
      analyze the participation of bats in the epidemiology of diseases caused by
      Bartonella, Coxiella, Rickettsia, Anaplasma and Ehrlichia, we conducted a
      descriptive epidemiological study in three biogeographic regions of the Brazilian
      Atlantic Forest. RESULTS: Tissues of 119 bats captured in preserved areas in the
      states of Rio de Janeiro, Bahia and Santa Catarina from 2014 to 2015 were
      submitted to molecular analysis using specific primers. Bartonella spp. was
      detected in 22 spleen samples (18.5%, 95% CI: 11.9-26.6), whose phylogenetic
      analysis revealed the generation of at least two independent clusters, suggesting
      that these may be new unique genotypes of Bartonella species. In addition, four
      samples (3.4%, 95% CI: 0.9-8.3) were positive for the htpAB gene of C. burnetii
      [spleen (2), liver (1) and heart (1)]. Rickettsia spp., Anaplasma and Ehrlichia
      were not identified. This is the first study reporting C. burnetii and Bartonella
      spp. infections in bats from the Atlantic Forest biome. CONCLUSIONS: These
      findings shed light on potential host range for these bacteria, which are
      characterized as important zoonotic pathogens.

PMID- 30200949
TI  - Factors associated with the use of outpatient services among the elderly in
      Indonesia.
AB  - BACKGROUND: Elderly people tend to have greater healthcare utilization because of
      their health status. However, with the 4th largest population in the world,
      little is known concerning the use of services among the Indonesian elderly.
      Hence, this study aimed to identify factors related to the use of outpatient
      services among the Indonesian elderly. METHODS: This is cross sectional study
      using data from the Indonesian Family Life Survey 5 (IFLS 5), conducted in 2014
      and 2015. Only those who were 60 years or older were included in the analyses. We
      used a logistic regression analysis to determine factors associated with use of
      outpatient services. RESULTS: Among 2912 participants, only 22.7% of respondents
      had visited health workers or doctors within the previous 4 weeks before the
      survey. After controlling for other variables, factors associated with the use of
      outpatient services were socioeconomic status, insurance status, regions of
      residence, self-rated health, and the number of chronic conditions. CONCLUSION:
      Inequality in outpatient services was observed among the elderly in Indonesia.
      More effort is need to expand insurance coverage for the elderly, particularly
      for those in the lower economic status, and to improve access to outpatient
      services in rural regions by allocating the needed resources.

PMID- 30200948
TI  - Weipixiao attenuate early angiogenesis in rats with gastric precancerous lesions.
AB  - BACKGROUND: Angiogenesis is a pathobiological hallmark of gastric cancer.
      However, rare studies focus on angiogenesis in gastric precancerous lesions
      (GPL). Weipixiao (WPX), a Chinese herbal preparation, is proved clinically
      effective in treating GPL. Here, we evaluated WPX's anti-angiogenic potential for
      GPL, and also investigated the possibility of its anti-angiogenic mechanisms.
      METHODS: HPLC analysis was applied to screen the major chemical components of
      WPX. After modeling N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced GPL in
      male Sprague-Dawley rats, different doses of WPX were administrated orally for 10
      weeks. Next, we performed histopathological examination using routine H&E
      staining and HID-AB-PAS staining. In parallel, we assessed angiogenesis revealed
      by microvessel density (MVD) using CD34 immunostaining, and subsequently observe
      microvessel ultrastructure in gastric mucosa under Transmission Electron
      Microscope. Finally, we detect expression of angiogenesis-associated markers VEGF
      and HIF-1alpha using immunohistochemistry. Moreover, mRNA expressions of ERK1,
      ERK2, Cylin D1 as well as HIF-1alpha in gastric mucosa were determined by
      quantitative real-time reverse transcription- polymerase chain reaction. RESULTS:
      We observed the appearance of active angiogenesis in GPL rats, and demonstrated
      that WPX could reduce microvascular abnormalities and attenuate early
      angiogenesis in most of GPL specimens with a concomitant regression of most
      intestinal metaplasia (IM) and a portion of gastric epithelial dysplasia (GED).
      In parallel, WPX could suppress HIF-1alpha mRNA expression (P < 0.01) as well as
      protein expression (although without statistical significance), and could
      markedly inhibit VEGF protein expression in GPL rats. Mechanistically, WPX
      intervention, especially at low dose, caused a significant decrease in the ERK1
      and Cylin D1 mRNA levels. However, WPX might probably have no regulatory effect
      on ERK2 amplification. CONCLUSIONS: WPX could attenuate early angiogenesis and
      temper microvascular abnormalities in GPL rats. This might be partly achieved by
      inhibiting on the angiogenesis-associated markers HIF-1alpha and VEGF, and on the
      ERK1/Cylin D1 aberrant activation.

PMID- 30200950
TI  - Impact of rehabilitation on mortality and readmissions after surgery for hip
      fracture.
AB  - BACKGROUND: Hip fracture in elderly patients is a rising global public health
      concern because of population ageing, and increasing frailty. Long-term morbidity
      related to poor management of hip fracture is associated with decreased quality
      of life, survival, and increase in healthcare costs. Receiving postoperative
      rehabilitation is associated with better outcomes and a higher likelihood of
      returning to pre-existing level of functioning. However little is known about
      which postoperative rehabilitation pathways are more effective to optimize
      patient outcomes. Few studies have analyzed postoperative rehabilitation pathways
      in a universal healthcare system. The aim of this study is to analyze the impact
      of post-acute rehabilitation pathways on mortality and readmission in elderly
      patients undergoing surgery for hip fracture in a large metropolitan area in
      Italy. METHODS: In this retrospective cohort study, we analyzed 6-month mortality
      from admission and 6-month readmission after hospital discharge in patients who
      underwent surgical repair for hip fracture in the hospitals of the Bologna
      metropolitan area between 1.1.2013 and 30.6.2014. Data were drawn from the
      regional hospital discharge records database. Kaplan-Meier estimates and multiple
      Cox regression were used to analyze mortality as a function of rehabilitation
      pathways. Multiple logistic regression determined predictors of readmission.
      RESULTS: The study population includes 2208 patients, mostly women (n = 1677,
      76%), with a median age of 83.8 years. Hospital rehabilitation was provided to
      519 patients (23.5%), 907 (41.1%) received rehabilitation in private inpatient
      rehabilitation facilities (IRF) accredited by the National Health System, and 782
      (35.4%) received no post-acute rehabilitation. Compared with patient receiving
      hospital rehabilitation, the other groups showed significantly higher mortality
      risks (no rehabilitation, Hazard Ratio (HR) = 2.19, 95%CI = 1.54-3.12, p < 0.001;
      IRF rehabilitation, HR = 1.66, 95%CI = 1.54-1.79, p < 0.001). The risk of
      readmission did not differ significantly among rehabilitation pathways.
      CONCLUSIONS: Intensive hospital rehabilitation was significantly associated with
      a lower risk of mortality compared to IRF rehabilitation and no rehabilitation.
      Our results may help in the development of evidence-based recommendations aimed
      to improve resource utilization and quality of care in hip fracture patients.
      Further research is warranted to investigate the impact of the rehabilitation
      pathway on other outcomes, such as patients' functional status and quality of
      life.

PMID- 30200951
TI  - A novel synthetic trivalent single chain variable fragment (tri-scFv)
      construction platform based on the SpyTag/SpyCatcher protein ligase system.
AB  - BACKGROUND: Advances in antibody engineering provide strategies to construct
      recombinant antibody-like molecules with modified pharmacokinetic properties.
      Multermerization is one strategy that has been used to produce antibody-like
      molecules with two or more antigen binding sites. Multimerization enhances the
      functional affinity (avidity) and can be used to optimize size and
      pharmacokinetic properties. Most multimerization strategies involve genetically
      fusing or non-covalently linking antibody fragments using oligomerization
      domains. Recent studies have defined guidelines for producing antibody-like
      molecules with optimal tumor targeting properties, which require intermediates
      size (70-120 kDa) and bi- or tri-valency. RESULTS: We described a highly modular
      antibody-engineering platform for rapidly constructing synthetic, trivalent
      single chain variable fragments (Tri-scFv) using the SpyCatcher/SpyTag protein
      ligase system. We used this platform to construct an anti-human epidermal growth
      factor receptor 3 (HER3) Tri-scFv. We generated the anti-HER3 Tri-scFv by
      genetically fusing a SpyCatcher to the C-terminus of an anti-HER3 scFv and
      ligating it to a synthetic Tri-SpyTag peptide. The anti-HER3 Tri-scFv bound
      recombinant HER3 with an apparent KD of 2.67 nM, which is approximately 12 times
      lower than the KD of monomeric anti-HER3 scFv (31.2 nM). Anti-HER3 Tri-scFv also
      bound endogenous cell surface expressed HER3 stronger than the monomer anti-HER3
      scFv. CONCLUSION: We used the SpyTag/SpyCatcher protein ligase system to ligate
      anti-HER3 scFv fused to a SpyCatcher at its C-termini to a Tri-SpyTag to
      construct Tr-scFv. This system allowed the construction of a Tri-scFv with all
      the scFv antigen-binding sites pointed outwards. The anti-HER3 Tri-scFv bound
      recombinant and endogenously expressed HER3 with higher functional affinity
      (avidity) than the monomeric anti-HER3 scFv. The Tri-scFv had the size, valency,
      and functional affinity that are desired for therapeutic and imaging
      applications. Use of the SpyTag/SpyCatcher protein ligase system allows Tri-scFvs
      to be rapidly constructed in a simple, modular manner, which can be easily
      applied to scFvs or other antibody fragments targeting other antigens.

PMID- 30200952
TI  - Sentinels of inequity: examining policy requirements for equity-oriented primary
      healthcare.
AB  - BACKGROUND: Non-government, not-for-profit community health centres (CHCs) play a
      crucial role within healthcare systems in fostering equity, acting both as direct
      providers of services and as sentinels of health and social inequity. In a study
      of an intervention to promote equity-oriented health care, we enlisted four
      diverse primary healthcare clinics with mandates to serve highly marginalized
      populations. All of these CHCs operate as not-for-profit, non-government
      organizations (NGOs), and have a marginal relationship financially and socially
      to other parts of the system. The purpose of this paper is to provide an analysis
      of the factors that shape how CHCs are able to carry out an equity mandate and,
      from this, to identify what is required at the level of policy to enhance
      capacity to provide equity-oriented health care. METHODS: We systematically
      examined the clinics' policy and funding contexts, and identified influences on
      the clinics' capacities to promote equity-oriented health care. RESULTS: We
      identified three key mechanisms of influence, each playing out against the
      backdrop of a contested and marginal position of CHCs within the health care
      system: a) accountability and performance frameworks; b) patterns of funding and
      allocation of resources, and c) pathways for emergent priorities. We examine
      these mechanisms, considering how each influenced the pursuit of equity, and
      propose policy directions to optimize the primary health care sectors' capacity
      to support equity-oriented health care. CONCLUSIONS: Although this analysis is
      based on a study within a high-income country, we argue that because the dynamics
      between community health centres and broader healthcare systems are similar
      across national boundaries, the implications have applicability to low and middle
      income countries.

PMID- 30200953
TI  - Sodium butyrate improves antioxidant stability in sub-acute ruminal acidosis in
      dairy goats.
AB  - BACKGROUND: Currently, little is known about the effect of sodium butyrate (NaB)
      on oxidative stress following grain-induced sub-acute ruminal acidosis in dairy
      goats. In the present study, 18 lactating dairy goats implanted with a ruminal
      cannula and permanent indwelling catheters in the portal and hepatic veins were
      randomly allocated into 3 treatment groups over 20 weeks: low grain (LG, 40%
      grain; n = 6), high grain (HG, 60% grain; n = 6) and high grain with sodium
      butyrate (HG + NaB, 60% grain + NaB; n = 6). RESULTS: When added to the HG diet,
      NaB increased the mean ruminal pH and reduced the levels of ruminal, portal and
      hepatic LPS; Additionally, we observed an increase in SOD1, SOD2, SOD3, GPX1 and
      CAT mRNA expression, increased levels of TSOD and CAT enzyme activity as well as
      increased total antioxidant capacity (T-AOC) and decreased malondialdehyde (MDA)
      in both the liver and plasma, while GPx activity increased in the liver of goats
      fed the HG + NaB diet. The mRNA expression of UGT1A1, NQO1, MGST3, and Nrf2, as
      well as total Nrf2 protein levels were increased in goats fed the HG + NaB diet.
      CONCLUSIONS: Our study indicates that sodium butyrate could improve the oxidative
      status in sub-acute ruminal acidosis through the partial activation of Nrf2
      dependent genes.

PMID- 30200954
TI  - Demand for health care service and associated factors among patients in the
      community of Tsegedie District, Northern Ethiopia.
AB  - BACKGROUND: Demand-side barriers are as important as supply factors in deterring
      patients from obtaining treatment. Developing countries including Ethiopia have
      been focusing on promoting health care utilization as an important policy to
      improve health outcomes and to meet international obligations to make health
      services broadly accessible. However, many policy and research initiatives
      focused on improving physical access rather than focusing on the pattern of
      health care service utilization related to demand side. Understanding of
      determinants of demand for health care services would enable to introduce and
      implement appropriate incentive schemes to encourage better utilization of health
      care services in the community of Tsegedie district, Northern Ethiopia. METHODS:
      A community based cross sectional study design was conducted from March1-30/2016
      in Northern Ethiopia. Systematic random sampling technique was used to select 423
      participants from 2189 patients of the one-month census. A pretested and
      standardized semi-structured interviewer administered questionnaire was used to
      collect the data. The data were entered using Epi-info version 7 and analysed by
      STATA version 11. Multinomial logistic regression model was used to identify the
      determinants of demand for health care service. RESULTS: A total of 423 (with a
      response rate of 98.3%) study participants were included in the study. The
      finding indicates that 72.5% (95%CI = 61.6, 81.1) of the participants demanded
      modern health care services. The multinomial logistic regression econometric
      model revealed that perceived severity of illness (beta = 1.27; 95% CI = 0.74,
      1.82), being educated household head (beta = 0.079; 95% CI = 0.96, 1.74), quality
      of treatment (beta = 0.99; 95% CI = 0.47, 1.5), distance to health facility beta
      = 1.96; 95%CI = 0.11, 0.27), cost of treatment (beta = - 1.99; 95% CI = 0.85,
      3,13) were significantly and statistically associated with demand for health care
      service. CONCLUSION: This study revealed that in Tsegedie district, majorities
      (72.5%) of the patients demanded modern health care service. Distance to health
      care facility, user-fees, educational status of household, quality of service,
      and severity of illness were found to be significantly associated with demand for
      health care service. Out of pocket, payments should be changed by prepayment
      schemes like community-based insurance than to depend on user fees and
      appropriate health information dissemination activities should strengthen to
      create awareness about modern care.

PMID- 30200955
TI  - Entertaining accurate treatment expectations while suffering from chronic pain:
      an exploration of treatment expectations and the relationship with patient-
      provider communication.
AB  - BACKGROUND: Accurate patient expectations are important to optimise treatment
      success, especially for complex conditions such as chronic pain. Communication
      may be the key to managing patient expectations. This study aimed to explore
      whether health care provider communication influences patient expectations and
      which communication aspects are most important. METHODS: We conducted secondary
      analyses on data that had been collected between September and November 2012.
      2603 patients suffering from chronic pain were invited to complete a survey.
      RESULTS: Although 69.9% of patients achieved or surpassed their treatment goal,
      30.2% of patients were unsatisfied. Even though overall health care provider
      communication and shared decision making were unrelated to patient expectations,
      several affective communication aspects were related. These aspects were
      attentive listening, taking enough time, building patient's trust in the
      physician's competence and giving patients the feeling that the physician is
      doing all he or she can (p's < 0.05). CONCLUSIONS: Even though treatment goals
      are not always explicitly discussed, patients still form expectations regarding
      treatment outcomes. Affective communication may be more important for managing
      patient expectations than sharing information. Building a good therapeutic
      relationship by showing affective communication may be important to increase the
      accuracy of patient expectations.

PMID- 30200957
TI  - Dementia subtype and living well: results from the Improving the experience of
      Dementia and Enhancing Active Life (IDEAL) study.
AB  - BACKGROUND: The heterogeneity of symptoms across dementia subtypes has important
      implications for clinical practice and dementia research. Variation in subtypes
      and associated symptoms may influence the capability to live well for people with
      dementia and carers. The aim of this study is to investigate the potential impact
      of dementia subtypes on the capability to live well for both people with dementia
      and their carers. METHODS: The analysis was based on the 1283 dyads of community
      dwelling people with dementia and carers in the Improving the experience of
      Dementia and Enhancing Active Life (IDEAL) project, a large cohort study in Great
      Britain. Capability to live well was defined using three measures: quality of
      life, life satisfaction and wellbeing. Structural equation modelling was used to
      investigate capability to live well in seven dementia subtypes: Alzheimer's
      disease (AD), Vascular dementia (VaD), mixed AD/VaD, frontotemporal dementia
      (FTD), Parkinson's disease dementia (PDD), Lewy body dementia (LBD) and
      unspecified/other, accounting for dyadic data structure and adjusting for age and
      sex, type of relationship between person with dementia and their carer and the
      number of chronic conditions. RESULTS: The major subtypes in this study
      population were AD (56%), VaD (11%) and mixed AD/VaD (21%). Compared to
      participants with AD, people with non-AD subtypes generally reported a lower
      capability to live well. Carers for people with PDD (- 1.71; 95% confidence
      interval (CI) - 3.24, - 0.18) and LBD (- 2.29; 95% CI - 3.84, - 0.75) also
      reported a lower capability to live well than carers for people with AD. After
      adjusting for demographic factors and comorbidity, PDD (- 4.28; 95% CI - 5.65, -
      2.91) and LBD (- 3.76; 95% CI - 5.14, - 2.39) continued to have the strongest
      impact on both people with dementia and their carers. CONCLUSIONS: This study
      suggests a variation in capability to live well across dementia subtypes. It is
      important for care providers to consider different needs across subtypes. Health
      professionals who provide post-diagnostic support may need to pay more attention
      to the complex needs of people living with PDD and LBD and their carers.

PMID- 30200956
TI  - Evolution of public hospitals expenditure by healthcare area in the Spanish
      National Health System: the determinants to pay attention to.
AB  - BACKGROUND: In Spain, hospital expenditure represents the biggest share of
      overall public healthcare expenditure, the most important welfare system directly
      run by the Autonomous Communities (ACs). Since 2001, public healthcare
      expenditure has increased well above the GDP growth, and public hospital
      expenditure increased at an even faster rate. This paper aims at assessing the
      evolution of need-adjusted public hospital expenditure at healthcare area level
      (HCA) and its association with utilisation and 'price' factors, identifying the
      relative contribution of ACs, as the main locus of health policy decisions.
      METHODS: Ecological study on public hospital expenditure incurred in 198 (HCAs)
      in 16 Spanish ACs, between 2003 and 2015. Aggregated and annual log-log
      multilevel models, considering ACs as a cluster, were modelled using
      administrative data. HCA expenditure was analysed according to differences in
      population need, utilization and price factors. Standardised coefficients were
      also estimated, as well as the variance partition coefficients. RESULTS: Between
      2003 and 2015, over 59 million hospital episodes were produced in Spain for an
      overall expenditure of ?384,200 million. Need-adjusted public hospital
      expenditure, at HCA level, was mainly associated to medical and surgical
      hospitalizations (standardized coefficients 0.32 and 0.28, respectively). The ACs
      explained 42% of the variance not explained by HCA utilization and 'price'
      factors. CONCLUSIONS: Utilization, rather than 'price' factors, may be explaining
      the difference in need-adjusted public hospital expenditure at HCA level in
      Spain. ACs, third-payers in the fully devolved Spanish National Health System,
      are responsible for a great deal of the variation in hospital expenditure.

PMID- 30200958
TI  - Neutralizing antibodies against Simbu serogroup viruses in cattle and sheep,
      Nigeria, 2012-2014.
AB  - BACKGROUND: Simbu serogroup viruses of the Orthobunyavirus genus (Family
      Peribunyaviridae) include teratogenic pathogens that cause severe economic
      losses, abortions, stillbirths and congenital abnormalities in ruminants
      worldwide. Although they were initially isolated from ruminants and Culicoides
      biting midges about five decades ago in Nigeria, there is no current information
      on their prevalence and geographical distribution despite reports of abortions
      and congenital malformations in the country's ruminant population. Here,
      apparently healthy cattle and sheep obtained from eight states in the three major
      vegetation zones of Nigeria were screened for the presence of specific
      neutralizing antibodies against Schmallenberg virus (SBV), Simbu virus (SIMV) and
      Shamonda virus (SHAV). RESULTS: Using a cross-sectional design, 490 cattle and
      165 sheep sera were collected between 2012 and 2014 and tested by a commercial
      SBV ELISA kit which enables the detection of antibodies against various Simbu
      serogroup viruses. The seropositivity rates for cattle and sheep were 91.2% and
      65.4%, respectively. In cattle, there was no association between ELISA
      seropositivity and vegetation zone. However, the prevalence of anti-Simbu
      serogroup antibodies was significantly higher in Ebonyi State compared to other
      states in the rainforest vegetation zone. The seroprevalence was significantly
      higher in sheep obtained from live animal markets compared to farms (OR = 5.8).
      Testing of 20 selected ELISA-positive sera by serum neutralisation test showed
      that all were positive for one or more of SBV, SIMV and SHAV with the highest
      titres obtained for SHAV. Antibodies to SBV or a closely related virus were
      detected in the Sudan savannah and rainforest zones, anti-SIMV antibodies were
      detected only in the rainforest zone, while anti-SHAV antibodies were found in
      the three vegetation zones. CONCLUSION: The findings of this study reveal that
      following the early isolation of Simbu serogroup viruses in Nigeria in the 1960s,
      members of this virus group are still circulating in the country. Specifically,
      SBV, SIMV and SHAV or closely related viruses infect cattle and sheep across the
      three vegetation zones of Nigeria suggesting that insect vector activity is
      extensive in the country. The exact vegetation zone where the animals became
      exposed to the viruses could, however, not be determined in this study.

PMID- 30200959
TI  - Glycaemic control for people with type 2 diabetes in Saudi Arabia - an urgent
      need for a review of management plan.
AB  - BACKGROUND: The aim of this study was to assess inadequate glycaemic control and
      its associated factors among people with type 2 diabetes in Saudi Arabia.
      METHODS: A cross-sectional study design was used. Adults with type 2 diabetes
      attending diabetes centres in Riyadh, Hofuf and Jeddah cities were interviewed
      and their anthropometrics were measured. Their medical records were also reviewed
      to collect information related to recent lab tests, medications, and documented
      comorbidities. Multivariable logistic regression were used for data analysis.
      RESULTS: A total of 1111 participants were recruited in the study. Mean age was
      57.6 (+/-11.1) years, 65.2% of the participants were females, and mean HbA1c was
      8.5 +/- 1.9%. About three-fourths of participants had inadequate glycaemic
      control (>= 7%). Multivariable analysis showed that age <= 60 years, longer
      duration of diabetes, living in a remote location, low household income, low
      intake of fruits and vegetable, low level of physical activity, lack of knowledge
      about haemoglobin A1c, high waist-hip ratio, low adherence to medication, and
      using injectable medications were independent risk factors for inadequate
      glycaemic control. CONCLUSIONS: Inadequate glycaemic control is prevalent among
      people with type 2 diabetes in Saudi Arabia. In order to improve glycaemic
      control diabetes management plan should aim at controlling the modifiable risk
      factors which include low intake of fruits and vegetable, low level of physical
      activity, lack of knowledge about haemoglobin A1c, high waist-hip ratio, and low
      adherence to medications.

PMID- 30200960
TI  - Implementation of an interprofessional medication adherence program for HIV
      patients: description of the process using the framework for the implementation
      of services in pharmacy.
AB  - BACKGROUND: The community pharmacy center of the Department of Ambulatory Care
      and Community Medicine of the Policlinique Medicale Universitaire (PMU),
      Lausanne, Switzerland developed and implemented an interprofessional medication
      adherence program for chronic patients (IMAP). In 2014, a project was launched to
      implement the IMAP for HIV patients in a public non-academic hospital with the
      collaboration of community pharmacists in the Neuchatel area (Switzerland). This
      article aims to describe the different implementation stages and strategies of
      the project. METHODS: A posteriori description of the implementation process,
      including the conceptualization strategies and stages (exploration, preparation,
      operation, sustainability) using the Framework for the Implementation of Services
      in Pharmacy (FISpH). RESULTS: In 2014, an attending infectious disease physician
      and a nurse at a public hospital (Neuchatel, Switzerland) contacted the PMU to
      implement the IMAP in their setting in collaboration with community pharmacies.
      Five volunteer community pharmacies in Neuchatel were trained to deliver the
      program. Three factors were found to be essential to the successful launch and
      progress of the implementation project: the experience of the community pharmacy
      center of the PMU with the IMAP, the involvement of the PMU research team, and
      collaboration with an external start up (SISPha) to train and support
      pharmacists. During the operation stage, the most important strategy developed
      was that of regular meetings between all stakeholders. These allowed healthcare
      professionals to discuss the implementation progress, to address each
      stakeholder's expectations, and to exchange experiences to facilitate
      interprofessional collaboration and program delivery. Structural changes allowed
      the formalization of the activities at the hospital and in a community pharmacy.
      This formalization was identified as the transition step between the operation
      and the sustainability stages. CONCLUSIONS: The transfer of the IMAP for HIV
      patients to a non-academic setting and its implementation are feasible. However,
      implementation of a new model of pharmacy service such as IMAP implies a deep
      change in practice. A transitional external support and the allocation of
      sufficient resources to carry out the IMAP are essential for its long-term
      sustainability.

PMID- 30200961
TI  - Development of a vitrification method for preserving human myoblast cell sheets
      for myocardial regeneration therapy.
AB  - BACKGROUND: Tissue-engineered cardiac constructs have potential in the functional
      recovery of heart failure; however, the preservation of these constructs is
      crucial for the development and widespread application of this treatment. We
      hypothesized that tissue-engineered skeletal myoblast (SMB) constructs may be
      preserved by vitrification to conserve biological function and structure.
      RESULTS: Scaffold-free cardiac cell-sheet constructs were prepared from SMBs and
      immersed in a vitrification solution containing ethylene glycol, sucrose, and
      carboxyl poly-L-lysine. The cell sheet was wrapped in a thin film and frozen
      rapidly above liquid nitrogen to achieve vitrification (vitrification group, n =
      8); fresh, untreated SMB sheets (fresh group, n = 8) were used as the control.
      The cryopreserved SMB sheets were thawed at 2 days, 1 week, 1 month, and 3 months
      after cryopreservation for assessment. Thawed, cryopreserved SMB sheets were
      transplanted into rat hearts in a myocardial infarction nude rat model, and their
      effects on cardiac function were evaluated. Cell viability in the cardiac
      constructs of the vitrification group was comparable to that of the fresh group,
      independent of the period of cryopreservation (p > 0.05). The structures of the
      cell-sheet constructs, including cell-cell junctions such as desmosomes,
      extracellular matrix, and cell membranes, were maintained in the vitrification
      group for 3 months. The expression of cytokine genes and extracellular matrix
      proteins (fibronectin, collagen I, N-cadherin, and integrin alpha5) showed
      similar levels in the vitrification and fresh groups. Moreover, in an in vivo
      experiment, the ejection fraction was significantly improved in animals treated
      with the fresh or cryopreserved constructs as compared to that in the sham
      treated group (p < 0.05). CONCLUSIONS: Overall, these results show that the
      vitrification method proposed here preserves the functionality and structure of
      scaffold-free cardiac cell-sheet constructs using human SMBs after thawing,
      suggesting the potential clinical application of this method in cell-sheet
      therapy.

PMID- 30200962
TI  - Characteristics of owned dogs in rabies endemic KwaZulu-Natal province, South
      Africa.
AB  - BACKGROUND: Canine rabies has been enzootic in the dog population of the KwaZulu
      Natal province of South Africa since the mid-1970s and has been associated with
      high rates of human exposures and frequent transmissions to other domestic animal
      species. Several decades of control efforts, consisting primarily of mass
      vaccination programs, have previously failed to sufficiently curb rabies in the
      province. Despite this history of canine rabies, the target canine population has
      never been extensively studied or quantified. For efficient and effective
      vaccination campaign planning, the target population must be evaluated and
      understood. This study reports evaluated observations from survey records
      captured through a cross sectional observational study regarding canine
      populations and dog owners in rabies enzootic KwaZulu-Natal province, South
      Africa. The objective of this study was to aid government veterinary services in
      their current and ongoing efforts to eliminate canine rabies in the province by
      gaining information about the size and distribution of the owned dog population.
      RESULTS: Thirty-eight percent of the households owned one or more dogs, with
      rural areas surveyed containing a significantly higher number of owned dogs than
      urban areas. The mean dog/person ratio for this study was 1:7.7 (range 1:5.4
      1:31). The provincial sex ratio was 1.5:1 male to female, with the percentages
      for male dogs across the communities ranging from 53 to 61.5%. The age structure
      of this dog population indicates a high turnover rate. Dogs were kept mostly for
      guarding homes or livestock. Eighty-four percent of dogs had received a rabies
      vaccine at some point in their lifetime, almost all during a rabies campaign.
      CONCLUSIONS: The study indicates the majority of owned dogs can be handled by at
      least one member of the household, thus can be made readily accessible for rabies
      vaccination during a campaign. Characteristics of owned dogs in the province were
      similar to those studied in other African countries; however, there were
      remarkable differences in age, sex and husbandry practices compared to dogs in
      eastern or northern Africa. These geographical differences lend credence to the
      theory that canine populations are heterogeneous; therefore, target populations
      should be evaluated prior to intervention planning.

PMID- 30200963
TI  - Sargassum horneri (Turner) C. Agardh ethanol extract inhibits the fine dust
      inflammation response via activating Nrf2/HO-1 signaling in RAW 264.7 cells.
AB  - BACKGROUND: Among the different kinds of pollution, air pollution continues to
      increase globally. East Asia is considered to be significantly affected. As a
      result, the populations in these regions face serious health issues including
      respiratory disorders. This study investigated the impact of fine dust (FD)
      particles (CRM No. 28) on macrophage cells as a model for alveolar lung cells.
      METHODS: The research focused on inflammation and oxidative stress induced by FD
      and Sargassum horneri (Turner) C. Agardh ethanol extract (SHE) as a potential
      treatment. S. horneri is a type of brown algae that has demonstrated anti
      inflammatory effects against RAW 264.7 macrophages in previous studies. MTT,
      Griess, ELISA, western blotting, and mRNA expression analyses using PCR
      techniques were used in this study. RESULTS: The optimum FD concentration was
      determined to be 125 MUg mL- 1. FD particles stimulated inflammatory mediators
      production (iNOS, COX-2, and PGE2) and pro-inflammatory cytokines (IL-1beta, IL
      6, and TNF-alpha), leading to NO production. These mediators were dose
      dependently downregulated by treatment with SHE. IL-6 and TNF-alpha were
      identified as biomarkers for FD. SHE treatment induced HO-1 and Nrf2 activity in
      a dose-dependent manner under FD stimulation. This confirmed the cytoprotective
      effect against oxidative stress induced via FD. Furthermore, treatment of the
      cells with a p38 MAPK inhibitor (SB202190) induced FD-stimulated NO production.
      CONCLUSIONS: The results suggest that SHE increases macrophage cellular
      resistance to FD-induced inflammation and oxidative stress, probably via the p38
      MAPK pathway and Nrf2/HO-1 expression.

PMID- 30200964
TI  - Meeting need vs. sharing the market: a systematic review of methods to measure
      the use of private sector family planning and childbirth services in sub-Saharan
      Africa.
AB  - BACKGROUND: Ensuring universal access to maternal and reproductive health
      services is critical to the success of global efforts to reduce poverty and
      inequality. Engaging private providers has been proposed as a strategy for
      increasing access to healthcare in low- and middle-income countries; however,
      little consensus exists on how to estimate the extent of private sector use.
      Using research from sub-Saharan Africa, this study systematically compares and
      critiques quantitative measures of private sector family planning and childbirth
      service use and synthesizes evidence on the role of the private sector in the
      region. METHODS: We conducted a systematic review of the Medline, Global Health,
      and Popline databases. All studies that estimated use of private sector of family
      planning or childbirth services in one or more sub-Saharan African countries were
      included in this review. For each study, we extracted data on the key study
      outcomes and information on the methods used to estimate private sector use.
      RESULTS: Fifty-three papers met our inclusion criteria; 31 provided outcomes on
      family planning, and 26 provided childbirth service outcomes. We found
      substantial methodological variation between studies; for instance, while some
      reported on service use from any private sector source, others distinguished
      private sector providers either by their profit orientation or position within or
      outside the formal medical sector. Additionally, studies measured the use of
      private sector services differently, with some estimating the proportion of need
      met by the private sector and others examining the sector's share among the
      market of service users. Overall, the estimates suggest that the private sector
      makes up a considerable portion (> 20%) of the market for family planning and
      childbirth care, but its role in meeting women's need for these services is
      fairly low (< 10%). CONCLUSIONS: Many studies have examined the extent of private
      sector family planning and childbirth service provision; however, inconsistent
      methodologies make it difficult to compare results across studies and contexts.
      Policymakers should consider the implications of both private market share and
      coverage estimates, and be cautious in interpreting data on the scale of private
      sector health service provision without a clear understanding of the methodology.

PMID- 30200965
TI  - Identifying the associated risks of pneumonia in COPD patients: ARCTIC an
      observational study.
AB  - BACKGROUND: Inhaled corticosteroids (ICS) are associated with an increased risk
      of pneumonia in patients with chronic obstructive pulmonary disease (COPD). Other
      factors such as severity of airflow limitation and concurrent asthma may further
      raise the possibility of developing pneumonia. This study assessed the risk of
      pneumonia associated with ICS in patients with COPD. METHODS: Electronic Medical
      Record data linked to National Health Registries were collected from COPD
      patients and matched reference controls in 52 Swedish primary care centers (2000
      2014). Levels of ICS treatment (high, low, no ICS) and associated comorbidities
      were assessed. Patients were categorized by airflow limitation severity. RESULTS:
      A total of 6623 patients with COPD and 48,566 controls were analyzed. Patients
      with COPD had a more than 4-fold increase in pneumonia versus reference controls
      (hazard ratio [HR] 4.76, 95% confidence interval [CI]: 4.48-5.06). ICS use
      increased the risk of pneumonia by 20-30% in patients with COPD with forced
      expiratory volume in 1 s >= 50% versus patients not using ICS. Asthma was an
      independent risk factor for pneumonia in the COPD population. Multivariate
      analysis identified independent predictors of pneumonia in the overall
      population. The highest risk of pneumonia was associated with high dose ICS (HR
      1.41, 95% CI: 1.23-1.62). CONCLUSIONS: Patients with COPD have a greater risk of
      pneumonia versus reference controls; ICS use and concurrent asthma increased the
      risk of pneumonia further.

PMID- 30200966
TI  - Combined diffusing capacity for nitric oxide and carbon monoxide as predictor of
      bronchiolitis obliterans syndrome following lung transplantation.
AB  - BACKGROUND: There is a need for non-invasive parameters that are sensitive to the
      development of the bronchiolitis obliterans syndrome (BOS) in lung
      transplantation (LTx) patients. We studied whether the pulmonary diffusing
      capacity for inhaled nitric oxide is capable of detecting BOS stages. METHODS:
      Sixty-one LTx patients were included into this cross-sectional study (19/29/7/3/3
      in BOS stages 0/0-p/1/2/3). For analysis stages 0/0-p versus 1/2/3 ("BOS binary
      early"), and stages 0/0-p/1 versus 2/3 ("BOS binary-late") were summarized.
      Measurements of the combined diffusing capacity for nitric oxide (DLNO) and
      carbon monoxide (DLCO) were compared with spirometry and bodyplethysmography, and
      their relative importance was evaluated by discriminant analysis. RESULTS:
      Regarding the recognition of "BOS binary-early", among spirometric parameters
      forced expiratory volume in 1 s (FEV1) was best, among bodyplethysmographic
      parameters airway resistance, and among diffusing parameters DLNO. Regarding "BOS
      binary-late", DLNO was inferior to bodyplethysmographic parameters. CONCLUSION:
      Although the study comprised only measurements at a single time point and no
      follow-up, DLNO outperformed FEV1, the time course of which is used in detecting
      BOS. Together with its pathophysiological plausibility, this result suggests that
      the measurement of DLNO, possibly over time, could be an easily applicable tool
      for the monitoring of LTx patients and should be evaluated in larger studies.

PMID- 30200967
TI  - Type 2 diabetes is independently associated with all-cause mortality secondary to
      ventricular tachyarrhythmias.
AB  - OBJECTIVES: The study sought to assess the prognostic impact of type 2 diabetes
      in patients presenting with ventricular tachyarrhythmias on admission.
      BACKGROUND: Data regarding the prognostic outcome of diabetics presenting with
      ventricular tachyarrhythmias is limited. METHODS: A large retrospective registry
      was used including all consecutive patients presenting with ventricular
      tachycardia (VT) and fibrillation (VF) on admission from 2002 to 2016. Patients
      with type 2 diabetes (diabetics) were compared to non-diabetics applying
      multivariable Cox regression models and propensity-score matching for evaluation
      of the primary prognostic endpoint of long-term all-cause mortality at 2 years.
      Secondary prognostic endpoints were cardiac death at 24 h, in-hospital death at
      index, all-cause mortality at 30 days, all-cause mortality in patients surviving
      index hospitalization at 2 years (i.e. "after discharge") and rehospitalization
      due to recurrent ventricular tachyarrhythmias at 2 years. RESULTS: In 2411
      unmatched high-risk patients with ventricular tachyarrhythmias, diabetes was
      present in 25% compared to non-diabetics (75%). Rates of VT (57% vs. 56%) and VF
      (43% vs. 44%) were comparable in both groups. Multivariable Cox regression models
      revealed diabetics associated with the primary endpoint of long-term all-cause
      mortality at 2 years (HR = 1.513; p = 0.001), which was still proven after
      propensity score matching (46% vs. 33%, log rank p = 0.001; HR = 1.525; p =
      0.001). The rates of secondary endpoints were higher for in-hospital death at
      index, all-cause mortality at 30 days, as well as after discharge, but not for
      cardiac death at 24 h or rehospitalization due to recurrent ventricular
      tachyarrhythmias. CONCLUSION: Presence of type 2 diabetes is independently
      associated with an increase of all-cause mortality in patients presenting with
      ventricular tachyarrhythmias on admission.

PMID- 30200968
TI  - Community boundary spanners as an addition to the health workforce to reach
      marginalised people: a scoping review of the literature.
AB  - BACKGROUND: Health services in high-income countries increasingly recognise the
      challenge of effectively serving and engaging with marginalised people. Effective
      engagement with marginalised people is essential to reduce health disparities
      these populations face. One solution is by tapping into the phenomenon of
      boundary-spanning people in the community-those who facilitate the flow of ideas,
      information, activities and relationships across organisation and socio-cultural
      boundaries. METHODS: A scoping review methodology was applied to peer-reviewed
      articles to answer the question: "How do health services identify, recruit and
      use boundary spanners and what are the outcomes?" The review was conducted in
      seven databases with search terms based on community-based boundary spanning,
      marginalised people and health services. FINDINGS: We identified 422 articles
      with the screening process resulting in a final set of 30 articles. We identified
      five types of community-based boundary spanning: navigators, community health
      workers, lay workers, peer supporters and community entities. These range from
      strong alignment to the organisation through to those embedded in the community.
      We found success in four domains for the organisation, the boundary spanner, the
      marginalised individuals and the broader community. Quantifiable outcomes related
      to cost-savings, improved disease management and high levels of clinical care.
      Outcomes for marginalised individuals related to improved health knowledge and
      behaviours, improved health, social benefits, reduced barriers to accessing
      services and increased participation in services. We identified potential
      organisational barriers to using boundary spanners based on organisational
      culture and staff beliefs. CONCLUSIONS: Community boundary spanners are a
      valuable adjunct to the health workforce. They enable access to hard to reach
      populations with beneficial health outcomes. Maintaining the balance of
      organisational and community alignment is key to ongoing success and diffusion of
      this approach.

PMID- 30200969
TI  - "They do not see us as one of them": a qualitative exploration of mentor mothers'
      working relationships with healthcare workers in rural North-Central Nigeria.
AB  - BACKGROUND: In HIV programs, mentor mothers (MMs) are women living with HIV who
      provide peer support for other women to navigate HIV care, especially in the
      prevention of mother-to-child transmission of HIV (PMTCT). Nigeria has
      significant PMTCT program gaps, and in this resource-constrained setting, lay
      health workers such as MMs serve as task shifting resources for formal healthcare
      workers and facility-community liaisons for their clients. However, challenging
      work conditions including tenuous working relationships with healthcare workers
      can reduce MMs' impact on PMTCT outcomes. This study explores the experiences and
      opinions of MMs with respect to their work conditions and relationships with
      healthcare workers. METHODS: This study was nested in the prospective two-arm
      Mother Mentor (MoMent) study, which evaluated structured peer support in PMTCT.
      Thirty-six out of the 38 MMs who were ever engaged in the MoMent study were
      interviewed in seven focus group discussions, which focused on MM workload and
      stipends, scope of work, and relationships with healthcare workers. English and
      English-translated Hausa-language transcripts were manually analyzed by theme and
      content in a grounded theory approach. RESULTS: Both intervention and control-arm
      MMs reported positive and negative relationships with healthcare workers,
      modulated by individual healthcare worker and structural factors. Issues with
      facility-level scope of work, workplace hierarchy, exclusivism and
      stigma/discrimination from healthcare workers were discussed. MMs identified
      clarification, formalization, and health system integration of their roles and
      services as potential mitigations to tenuous relationships with healthcare
      workers and challenging working conditions. CONCLUSIONS: MMs function in multiple
      roles, as task shifting resources, lay community health workers, and peer
      counselors. MMs need a more formalized, well-defined niche that is fully
      integrated into the health system and is responsive to their needs. Additionally,
      the definition and formalization of MM roles have to take healthcare worker
      orientation, sensitization, and acceptability into consideration. TRIAL
      REGISTRATION: Clinicaltrials.gov number NCT01936753 , registered September 3,
      2013.

PMID- 30200970
TI  - Correction to: Analysis of anti-malarial resistance markers in pfmdr1 and pfcrt
      across Southeast Asia in the Tracking Resistance to Artemisinin Collaboration.
AB  - Following publication of the original article [1], one of the authors has
      highlighted an xml-related discrepancy concerning the author group titled
      'Additional Tracking Resistance to Artemisinin Collaboration authors (TRAC Group
      Authorship)', listed under the Acknowledgements section.

PMID- 30200972
TI  - Assessment of thyroid cancer risk in more than 334,000 patients with inflammatory
      bowel disease: a case-control study and a meta-analysis.
AB  - BACKGROUND: Potential risk of thyroid cancer in patients with inflammatory bowel
      disease has not been well investigated. The aim of the study was to reveal the
      relationship between history of inflammatory bowel disease and risk of thyroid
      cancer. METHODS: First, 1392 patients with inflammatory bowel disease and 1392
      controls were included in a case-control study. All patients did not receive
      immunosuppressive therapy. A multivariate logistic regression analysis was
      adopted to determine the relationship between history of inflammatory bowel
      disease and risk of thyroid cancer. Second, a literature search was performed and
      eight articles were collected. Pooled odds ratios with 95% confidence intervals
      were reported for relevant risk estimates in fixed or random effect model.
      RESULTS: In the case-control study, thyroid cancer was more common in patients
      with inflammatory bowel disease than in controls (P = 0.032). After Bonferroni
      correction, association of thyroid cancer risk with history of total inflammatory
      bowel disease or its two subtypes was not found. In the meta-analysis, patients
      with total inflammatory bowel disease or ulcerative colitis showed an increased
      risk of thyroid cancer, but patients with Crohn's disease did not. Furthermore,
      inflammatory bowel disease patients with immunosuppressive therapy showed an
      increased risk of the cancer, but patients without immunosuppressive therapy did
      not have this finding. CONCLUSIONS: Risk of thyroid cancer probably elevates in
      patients with inflammatory bowel disease. Inflammatory bowel disease
      (particularly ulcerative colitis) itself and use of immunosuppressant might
      contribute to the development of the cancer.

PMID- 30200971
TI  - Quality of life of parents of very preterm infants 4 months after birth: a mixed
      methods study.
AB  - BACKGROUND: Knowledge about parental quality of life (QoL) is paramount to family
      centred and integrated healthcare on prematurity, but evidence is limited. We
      aimed to explore mothers' and fathers' perspectives about their QoL 4 months
      after a very preterm childbirth. METHODS: This is a cross-sectional mixed methods
      study using a convergent design. Parents of very preterm infants were
      systematically recruited at all level III neonatal intensive care units in the
      Northern health region of Portugal for one year. Four months after childbirth, 61
      mothers and 56 fathers filled-in the World Health Organization Quality of Life -
      BREF Inventory, and 26 couples were interviewed. Linear regression models were
      computed to assess the association between participants' characteristics and the
      QoL. Qualitative data were thematically analysed. RESULTS: A quantitative
      analysis revealed that the perception of QoL was not significantly different by
      gender. QoL scores increased slightly from the environment (Mean (SD): 72.1
      (14.2)) to the psychological domains (Mean (SD): 78.7 (14.4)). All scores were
      influenced by psychological characteristics. Socioeconomic position influenced
      both parents' perceptions concerning the environment domain, and maternal
      physical and psychological QoL. Infant-related factors were associated with
      overall QoL among women and with the physical, psychological, social and
      environment domains among men. Qualitative findings indicated accommodation
      mechanisms that intertwine the focus on constraining factors (surveillance, sleep
      disturbances, non-supportive healthcare policies, hygienization) with
      facilitating factors (social support, accessibility/quality of healthcare,
      opportunities for developing parental skills). These processes were anchored in
      child-centredness and a framework that construct hierarchies of hope and
      expectations about infant's health and development. CONCLUSIONS: To capture
      parental QoL using mixed methods raises awareness for developing intersectoral
      family-centred policies, integrated health services and focused-interventions to
      decrease the disempowering effects of surveillance and hygienization.

PMID- 30200974
TI  - Correction to: Housing gaps, mosquitoes and public viewpoints: a mixed methods
      assessment of relationships between house characteristics, malaria vector biting
      risk and community perspectives in rural Tanzania.
AB  - Following publication of the original article [1], the author flagged that the
      clause "and competing household priorities" was missing from the second sentence
      of the conclusion section of the Abstract; while this clause was in the
      Conclusion section of the main article text.

PMID- 30200973
TI  - When to incorporate point-of-care ultrasound (POCUS) into the initial assessment
      of acutely ill patients: a pilot crossover study to compare 2 POCUS-assisted
      simulation protocols.
AB  - BACKGROUND: The purpose of this study was to determine the ideal timing for
      providers to perform point-of-care ultrasound (POCUS) with the least increase in
      workload. METHODS: We conducted a pilot crossover study to compare 2 POCUS
      assisted evaluation protocols for acutely ill patients: sequential (physical
      examination followed by POCUS) vs parallel (POCUS at the time of physical
      examination). Participants were randomly assigned to 2 groups according to which
      POCUS-assisted protocol (sequential vs parallel) was used during simulated
      scenarios. Subsequently, the groups were crossed over to complete assessment by
      using the other POCUS-assisted protocol in the same patient scenarios. Providers'
      workloads, measured with the National Aeronautics and Space Administration Task
      Load Index (NASA-TLX) and time to complete patient evaluation, were compared
      between the 2 protocols. RESULTS: Seven providers completed 14 assessments (7
      sequential and 7 parallel). The median (IQR) total NASA-TLX score was 30 (30-50)
      in the sequential and 55 (50-65) in the parallel protocol (P = .03), which
      suggests a significantly lower workload in the sequential protocol. When
      individual components of the NASA-TLX score were evaluated, mental demand and
      frustration level were significantly lower in the sequential than in the parallel
      protocol (40 [IQR, 30-60] vs 50 [IQR, 40-70]; P = .03 and 25 [IQR, 20-35] vs 60
      [IQR, 45-85]; P = .02, respectively). The time needed to complete the assessment
      was similar between the sequential and parallel protocols (8.7 [IQR, 6-9] minutes
      vs 10.1 [IQR, 7-11] minutes, respectively; P = .30). CONCLUSIONS: A sequential
      POCUS-assisted protocol posed less workload to POCUS operators than the parallel
      protocol.

PMID- 30200975
TI  - Engineering of 3-ketosteroid-?1-dehydrogenase based site-directed saturation
      mutagenesis for efficient biotransformation of steroidal substrates.
AB  - BACKGROUND: Biosynthesis of steroidal drugs is of great benefit in pharmaceutical
      manufacturing as the process involves efficient enzymatic catalysis at ambient
      temperature and atmospheric pressure compared to chemical synthesis. 3
      ketosteroid-?1-dehydrogenase from Arthrobacter simplex (KsdD3) catalyzes 1,2
      desaturation of steroidal substrates with FAD as a cofactor. RESULTS: Recombinant
      KsdD3 exhibited organic solvent tolerance. W117, F296, W299, et al., which were
      located in substrate-binding cavity, were predicted to form hydrophobic
      interaction with the substrate. Structure-based site-directed saturation
      mutagenesis of KsdD3 was performed with W299 mutants, which resulted in improved
      catalytic activities toward various steroidal substrates. W299A showed the
      highest increase in catalytic efficiency (kcat/Km) compared with the wild-type
      enzyme. Homology modelling revealed that the mutants enlarged the active site
      cavity and relieved the steric interference facilitating recognition of C17
      hydroxyl/carbonyl steroidal substrates. Steered molecular dynamics simulations
      revealed that W299A/G decreased the potential energy barrier of association of
      substrates and dissociation of the corresponding products. The biotransformation
      of AD with enzymatic catalysis and resting cells harbouring KsdD3 WT/mutants
      revealed that W299A catalyzed the maximum ADD yields of 71 and 95% by enzymatic
      catalysis and resting cell conversion respectively, compared with the wild type
      (38 and 75%, respectively). CONCLUSIONS: The successful rational design of
      functional KsdD3 greatly advanced our understanding of KsdD family enzymes.
      Structure-based site-directed saturation mutagenesis and biochemical data were
      used to design KsdD3 mutants with a higher catalytic activity and broader
      selectivity.

PMID- 30200976
TI  - FAF1 mediates necrosis through JNK1-mediated mitochondrial dysfunction leading to
      retinal degeneration in the ganglion cell layer upon ischemic insult.
AB  - BACKGROUND: Aberrant cell death induced by ischemic stress is implicated in the
      pathogenesis of ischemic diseases. Fas-associated factor 1 (FAF1) has been
      identified as a death-promoting protein. This study demonstrates that FAF1
      functions in death signaling triggered by ischemic insult. METHODS: The
      expression changes of FAF1 and phophorylated JNK1 were detected by Western
      blotting. Immunoprecipitation was employed to investigate protein-protein
      interaction. We determined the cell death using flow cytometry and lactate
      dehydrogenase release measurement. To validate the death-promoting role of FAF1
      in the retina, we generated conditional retinal FAF1 knockout mice. We used
      hematoxylin and eosin staining to detect retinal cell death in retinal ganglion
      cell layer. RESULTS: FAF1 was found to function upstream of c-Jun N-terminal
      kinase 1 (JNK1), followed by mitochondrial dysregulation and necrotic cell death
      processes upon ischemic insult. We investigated whether FAF1 is involved in the
      pathogenesis of ischemic diseases using a retinal ischemia model. Indeed, FAF1
      potentiated necrosis through JNK1 activation upon ischemic stress in retinal
      cells demonstrating retinal ganglion-like character. Conditional FAF1 depletion
      attenuated JNK1 activation in the retinas of Dkk3-Cre;Faf1flox/flox mice and
      ameliorated death of retinal cells due to elevated intraocular pressure (IOP).
      CONCLUSIONS: Our results show that FAF1 plays a key role in ischemic retinal
      damage and may be implicated in the pathogenesis of retinal ischemic disease.

PMID- 30200977
TI  - Reproducibility of Transcranial Doppler ultrasound in the middle cerebral artery.
AB  - BACKGROUND: Transcranial Doppler ultrasound remains the only imaging modality
      that is capable of real-time measurements of blood flow velocity and microembolic
      signals in the cerebral circulation. We here assessed the repeatability and
      reproducibility of transcranial Doppler ultrasound in healthy volunteers and
      patients with symptomatic carotid artery stenosis. METHODS: Between March and
      August 2017, we recruited 20 healthy volunteers and 20 patients with symptomatic
      carotid artery stenosis. In a quiet temperature-controlled room, two 1-h
      transcranial Doppler measurements of blood flow velocities and microembolic
      signals were performed sequentially on the same day (within-day repeatability)
      and a third 7-14 days later (between-day reproducibility). Levels of agreement
      were assessed by interclass correlation co-efficient. RESULTS: In healthy
      volunteers (31+/-9 years, 11 male), within-day repeatability of Doppler
      measurements were 0.880 (95% CI 0.726-0.950) for peak velocity, 0.867 (95% CI
      0.700-0.945) for mean velocity, and 0.887 (95% CI 0.741-0.953) for end-diastolic
      velocity. Between-day reproducibility was similar but lower: 0.777 (95% CI 0.526
      0.905), 0.795 (95% CI 0.558-0.913), and 0.674 (95% CI 0.349-0.856) respectively.
      In patients (72+/-11 years, 11 male), within-day repeatability of Doppler
      measurements were higher: 0.926 (95% CI 0.826-0.970) for peak velocity, 0.922
      (95% CI 0.817-0.968) for mean velocity, and 0.868 (95% CI 0.701-0.945) for end
      diastolic velocity. Similarly, between-day reproducibility revealed lower values:
      0.800 (95% CI 0.567-0.915), 0.786 (95% CI 0.542-0.909), and 0.778 (95% CI 0.527
      0.905) respectively. In both cohorts, the intra-observer Bland Altman analysis
      demonstrated acceptable mean measurement differences and limits of agreement
      between series of middle cerebral artery velocity measurements with very few
      outliers. In patients, the carotid stenoses were 30-40% (n = 9), 40-50% (n = 6),
      50-70% (n = 3) and > 70% (n = 2). No spontaneous embolisation was detected in
      either of the groups. CONCLUSIONS: Transcranial Doppler generates reproducible
      data regarding the middle cerebral artery velocities. However, larger studies are
      needed to validate its clinical applicability. TRIAL REGISTRATION:
      ClinicalTrial.gov (ID NCT 03050567), retrospectively registered on 15/05/2017.

PMID- 30200978
TI  - Increasing medium chain fatty acids production in Yarrowia lipolytica by
      metabolic engineering.
AB  - BACKGROUND: Oleaginous yeast Yarrowia lipolytica is an organism of choice for the
      development of biofuel and oleochemicals. It has become a chassis for metabolic
      engineering in order to produce targeted lipids. Understanding the function of
      key-enzymes involved in lipid metabolism is essential to design better routes for
      enhanced lipid production and for strains producing lipids of interest. Because
      medium chain fatty acids (MCFA) are valuable compounds for biokerosene
      production, we previously generated strains capable of producing MCFA up to 12%
      of total lipid content (Rigouin et al. in ACS Synth Biol 6:1870-1879, 2017). In
      order to improve accumulation and content of C14 fatty acid (FA), the elongation,
      degradation and accumulation of these MCFA in Yarrowia lipolytica were studied.
      RESULTS: We brought evidence of the role of YALI0F0654 (YlELO1) protein in the
      elongation of exogenous or de novo synthesized C14 FA into C16 FA and C18 FA.
      YlELO1 deletion into a alphaFAS_I1220W expressing strain leads to the sole
      production of C14 FA. However, because this strain does not provide the FA
      essential for its growth, it requires being cultivated with essential fatty acids
      and C14 FA yield is limited. To promote MCFA accumulation in Y. lipolytica
      without compromising the growth, we overexpressed a plant diglyceride
      acyltransferase specific for MCFA and reached an accumulation of MCFA up to 45%
      of total lipid content. CONCLUSION: We characterized the role of YlELO1 in Y.
      lipolytica by proving its involvement in Medium chain fatty acids elongation. We
      showed that MCFA content can be increased in Yarrowia lipolytica by promoting
      their accumulation into a stable storage form (triacylglycerides) to limit their
      elongation and their degradation.

PMID- 30200979
TI  - Uncemented, curved, short endoprosthesis stem for distal femoral reconstruction:
      early follow-up outcomes.
AB  - BACKGROUND: Uncemented endoprosthetic knee replacement has become a mainstream
      treatment for malignant tumours of the distal femur. Most femoral stems, however,
      are straight and therefore poorly fit the anteriorly bowed curvature of the
      femur. To address this issue, we used a short, curved, uncemented press-fit
      femoral stem and evaluated its short-term outcomes after reconstruction of the
      distal femur. METHODS: Forty-two patients underwent distal femur replacement
      using curved press-fit stem. To assess the interface, we measured the axial
      length of the press-fit area and the perpendicular distance of the radiolucent
      area between the stem and bone on digital images obtained using tomosynthesis
      with Shimadzu Metal Artefact Reduction Technology (T-SMART). Postoperative
      complications and oncological outcomes were monitored at each follow-up visit.
      RESULTS: Of the 42 patients enrolled in the study, two had cancer-related deaths
      and one had local tumour recurrence. The minimum follow-up time of the surviving
      patients was 24 months, with no incidence of aseptic loosening or mechanical
      failure of the prosthesis. The average effective contact length between the press
      fit stem and bone was 74.0 mm, with nearly undetectable radiolucent gaps between
      the implant and the bone on medial-lateral and anteroposterior views.
      CONCLUSIONS: Over the short term, uncemented, curved, short stem provides a
      stable bone-prosthesis interface without any aseptic loosening.

PMID- 30200980
TI  - Domain-specific physical activity and affective wellbeing among adolescents: an
      observational study of the moderating roles of autonomous and controlled
      motivation.
AB  - BACKGROUND: Abundant evidence demonstrates a relationship between physical
      activity and mental wellbeing. However, the strength of the relationship is not
      consistent. Factors contributing to variation in the strength of association are
      not well understood and, therefore, it remains difficult to optimize physical
      activity to ensure the strongest possible relationship with mental health. Self
      determination theory suggests that more autonomously motivated behaviors lead to
      better mental health outcomes, when compared to more controlled behaviors.
      Therefore, we examined whether autonomous and controlled motivation moderated the
      relationships between physical activity and affective wellbeing within two
      domains (i.e., leisure-time and active travel). METHODS: Between February and
      April 2014, adolescents (N = 1632, M age = 12.94 years, SD = 0.54, 55% male) wore
      an accelerometer across seven-days and completed self-report measures of leisure
      time physical activity and active travel. They also completed two measures of
      motivation (towards leisure-time physical activity and active travel) and an
      affective wellbeing measure. RESULTS: Structural equation modeling revealed that
      greater self-reported leisure-time physical activity was associated with greater
      positive affect (beta = .29) and less negative affect (beta = -.19) and that
      motivation did not moderate these relationships. Self-reported active travel had
      no linear relationship with affective wellbeing, and motivation did not moderate
      these relationships. Accelerometer-measured leisure-time physical activity had no
      relationship with positive affect but, had a weak inverse association with
      negative affect (beta = -.09), and neither relationship was moderated by
      motivation. Accelerometer-measured active travel had no association with positive
      affect; however, autonomous motivation significantly moderated this association
      such that active travel had a positive association with positive affect when
      autonomous motivation was high (beta = .09), but a negative association when
      autonomous motivation was low (beta = -.07). Accelerometer-measured active travel
      had no association with negative affect. Despite some significant moderation
      effects, motivation did not consistently moderate the relationship between all
      physical activity variables (leisure-time and active travel, and self-report and
      accelerometer) and affective outcomes. CONCLUSIONS: Tailoring physical activity
      interventions and guidelines to prioritize leisure-time ahead of other life
      domains could benefit wellbeing. Promoting autonomous participation in active
      travel may also be associated with increased wellbeing among adolescents.

PMID- 30200982
TI  - Mapping of the Gastrointestinal Short Form Questionnaire (GSF-Q) into EQ-5D-3L
      and SF-6D in patients with gastroesophageal reflux disease.
AB  - BACKGROUND: The short, self-administered Gastroesophageal Reflux Disease (GERD)
      Symptom Frequency Questionnaire (GSFQ) is a specific Quality of Life (QoL)
      instrument which measures the impact of GERD symptoms on QoL. This study aims to
      map the specific scores in GSFQ into two generic instruments: SF-6D and EQ-5D-3
      L, in order to obtain utility estimates derived from the GERD condition. METHOD:
      A national representative sample of GERD patients was selected, stratified by
      gender, age (< 45, >=45 years) and GERD severity (0-I, II-IV Savary-Miller score)
      for validation purposes. Age, gender, BMI, GERD diagnose, GERD severity,
      associated comorbidities and risk factors were recorded. GSFQ, SF-6D, EQ-5D-3 L,
      and the HRQoL Visual Analogue Scale (VAS) were answered by patients. Several
      mapping methods were estimated, regression using dummy variables, and linear,
      quadratic and cubic regression using optimal factor scores. The use of a GERD
      aggregated summary severity derived from the GSFQ was dimed the best predictor.
      Overall Mean Absolute Error (MAE), overall Mean Absolute Percentage Error (MAPE)
      were used as goodness-of-fit (GOF) indexes to compare models. RESULTS: A total of
      3405 patients were recruited by 490 clinicians. Mean age was 49 (+/-14.4) years
      and 49.8% were women. Reported comorbidities were clustered in 6 antecedents and
      15 concomitant pathologies. Aggregation of levels for the frequency of symptoms
      items was found more suitable for estimation. Regression weights were found to
      follow a monotonous progressive pattern. Overall MAE ranged from 0.092 to 0.094
      for SF-6D utility prediction and from 0.008 to 0.08 for EQ-5D-3 L, while MAPE
      values ranged from 27.9 to 29% for SF-6D and from 36.8 to 38.4% for EQ-5D-3 L.
      Cubic regression GOF demonstrated a better fit. CONCLUSIONS: It is possible to
      translate specific GSFQ scores assessing GERD condition into generic SF-6D and EQ
      5D-3 L utility values. Although regression using dummy variables is a suitable
      mapping procedure, other alternative mapping methods convey better fit, in
      particular cubic regression.

PMID- 30200983
TI  - Triglyceride to high density lipoprotein cholesterol ratio among adolescents is
      associated with adult hypertension: the Kangwha study.
AB  - BACKGROUND: The triglyceride to high density lipoprotein cholesterol (TG/HDL-C)
      ratio associated with hypertension in adults. However, whether the TG/HDL-C ratio
      in adolescents predicts future hypertension remains unclear. Here, we evaluated
      the prospective association between the TG/HDL-C ratio in adolescents and
      hypertension in early adulthood. METHODS: The Kangwha Study is an ongoing
      prospective cohort study that has tracked the blood pressure of first grade
      elementary school students since 1986. We followed up 272 participants who
      completed health examinations at the age of 16 and 35 years. We excluded 27
      participants with adolescent hypertension, defined as those whose blood pressures
      were above the age- and sex-specific 95th percentiles of the Korean population,
      and finally analysed 245 participants. We defined high and low TG/HDL-C ratio
      groups according to the age- and sex-specific 75th percentile of the TG/HDL-C
      ratio (1.04 for boys and 0.81 for girls) of the Korean population. Adult
      hypertension was defined by a systolic/diastolic blood pressure >= 140/90 mmHg or
      by taking antihypertensive medication at the age of 35 years. Logistic regression
      analysis was performed to evaluate the association between adolescent TG/HDL-C
      ratio and adult hypertension after adjusting for age at follow-up, sex, baseline
      systolic blood pressure, waist circumference, and total cholesterol and fasting
      glucose levels. RESULTS: During the 20-year follow-up, 11 (18.3%) individuals
      developed hypertension in the high TG/HDL-C ratio group and 10 (5.4%) individuals
      developed hypertension in the low TG/HDL-C ratio group. The adjusted odds ratio
      for incident hypertension in the high TG/HDL-C ratio group, compared with the low
      TG/HDL-C ratio group, was 3.40 (95% confidence interval 1.24-9.31). CONCLUSIONS:
      High TG/HDL-C ratio in adolescence is associated with hypertension in early
      adulthood.

PMID- 30200981
TI  - Comprehensive off-target analysis of dCas9-SAM-mediated HIV reactivation via long
      noncoding RNA and mRNA profiling.
AB  - BACKGROUND: CRISPR/CAS9 (epi)genome editing revolutionized the field of gene and
      cell therapy. Our previous study demonstrated that a rapid and robust
      reactivation of the HIV latent reservoir by a catalytically-deficient Cas9
      (dCas9)-synergistic activation mediator (SAM) via HIV long terminal repeat (LTR)
      specific MS2-mediated single guide RNAs (msgRNAs) directly induces cellular
      suicide without additional immunotherapy. However, potential off-target effect
      remains a concern for any clinical application of Cas9 genome editing and dCas9
      epigenome editing. After dCas9 treatment, potential off-target responses have
      been analyzed through different strategies such as mRNA sequence analysis, and
      functional screening. In this study, a comprehensive analysis of the host
      transcriptome including mRNA, lncRNA, and alternative splicing was performed
      using human cell lines expressing dCas9-SAM and HIV-targeting msgRNAs. RESULTS:
      The control scrambled msgRNA (LTR_Zero), and two LTR-specific msgRNAs (LTR_L and
      LTR_O) groups show very similar expression profiles of the whole transcriptome.
      Among 839 identified lncRNAs, none exhibited significantly different expression
      in LTR_L vs. LTR_Zero group. In LTR_O group, only TERC and scaRNA2 lncRNAs were
      significantly decreased. Among 142,791 mRNAs, four genes were differentially
      expressed in LTR_L vs. LTR_Zero group. There were 21 genes significantly
      downregulated in LTR_O vs. either LTR_Zero or LTR_L group and one third of them
      are histone related. The distributions of different types of alternative splicing
      were very similar either within or between groups. There were no apparent changes
      in all the lncRNA and mRNA transcripts between the LTR_L and LTR_Zero groups.
      CONCLUSION: This is an extremely comprehensive study demonstrating the rare off
      target effects of the HIV-specific dCas9-SAM system in human cells. This finding
      is encouraging for the safe application of dCas9-SAM technology to induce target
      specific reactivation of latent HIV for an effective "shock-and-kill" strategy.

PMID- 30200984
TI  - Movement artefact removal from NIRS signal using multi-channel IMU data.
AB  - BACKGROUND: The non-invasive nature of near-infrared spectroscopy (NIRS) makes it
      a widely accepted method for blood oxygenation measurement in various parts of
      the human body. One of the main challenges in this method lies in the successful
      removal of movement artefacts in the detected signal. In this respect, multi
      channel inertia measurement unit (IMU) containing accelerometer, gyroscope and
      magnetometer can be used for better modelling of movement artefact than using
      accelerometer only, which as a result, movement artefact can be more accurately
      removed. METHODS: A wearable two-channel continuous wave NIRS system,
      incorporating an IMU sensor which contain accelerometer, gyroscope and
      magnetometer in it, was developed to record NIRS signal along with the
      simultaneous recording of movement artefacts related signal using the IMU. Four
      healthy subjects volunteered in the recording of the NIRS signals. During the
      recording from the first two subject, movement artefacts were simulated in one of
      the NIRS channels by tapping the photodiode sensor nearby. The corresponding IMU
      data for the simulated movement artefacts were used to estimate the artefacts in
      the corrupted signal by autoregressive with exogenous input method and subtracted
      from the corrupted signal to remove the artefacts in the NIRS signal. Signal-to
      noise ratio (SNR) improvement was used to evaluate the performance of the
      movement artefacts removal process. The performance of the movement artefacts
      estimation and removal were compared using accelerometer only, accelerometer and
      gyroscope, and accelerometer, gyroscope and magnetometer data from IMU sensor to
      estimate the artefact in NIRS reading. For the remaining two subjects the NIRS
      signal was recorded by natural movement artefacts impact and the results of
      artefacts removal was compared using accelerometer only, accelerometer and
      gyroscope, and accelerometer, gyroscope and magnetometer data from IMU sensor to
      estimate the artefact in NIRS reading. RESULTS: The quantitative and qualitative
      results revealed that the SNR improvement increases with the number of IMU
      channels used in the artefacts estimation, and there were approximately 5-11 dB
      increase in SNR when nine channel IMU data were used rather than using only three
      channel accelerometer data only. The artefact removal from natural movements also
      demonstrated that the combination of gyroscope and magnetometer sensors with
      accelerometer provided better estimation and removal of the movement artefacts,
      which was revealed by the minimal change of the HbO2 and Hb level before, during
      and after movement artefacts occurred in the NIRS signal. CONCLUSION: The
      movement artefacts in NIRS can be more accurately estimated and removed by using
      accelerometer, gyroscope and magnetograph signals from an integrated IMU sensor
      than using accelerometer signal only.

PMID- 30200985
TI  - Introducing responsible innovation in health: a policy-oriented framework.
AB  - The scholarship on responsible research and innovation (RRI) aims to align the
      processes and outcomes of innovation with societal values by involving a broad
      range of stakeholders from a very early stage. Though this scholarship offers a
      new lens to consider the challenges new health technologies raise for health
      systems around the world, there is a need to define the dimensions that
      specifically characterise responsible innovation in health (RIH). The present
      article aims to introduce an integrative RIH framework drawing on the RRI
      literature, the international literature on health systems as well as specific
      bodies of knowledge that shed light on key dimensions of health innovations.
      Combining inductive and deductive theory-building strategies and concomitant with
      the development of a formal tool to assess the responsibility of innovations, we
      developed a framework that is comprised of nine dimensions organised within five
      value domains, namely population health, health system, economic, organisational
      and environmental. RIH provides health and innovation policy-makers with a common
      framework that supports the development of innovations that can tackle
      significant system-level challenges, including sustainability and equity.

PMID- 30200986
TI  - Increasing women's engagement in vector control: a report from Accelerate To
      Equal project workshops.
AB  - Workshops with academic, national and local government, and community
      stakeholders were held in Kenya (2017) and Indonesia (2018) to understand the
      role and perceptions of women in vector control and to identify strategies for
      accelerating involvement of women in sustained support for vector control
      interventions at multiple levels/sectors.

PMID- 30200988
TI  - How to keep registered nurses working in New Zealand even as economic conditions
      improve.
AB  - BACKGROUND: Many registered nurses (RNs) increased their participation in the New
      Zealand health workforce during the Global Financial Crisis (GFC), resulting in
      low vacancy rates. However, based on the documented impact of improving
      economies, a mean RN age of about 50, and just-agreed substantive increases in RN
      pay rates, it is likely that many will soon leave or reduce the hours they work.
      This study aims to investigate whether improved financial security will encourage
      RNs to leave or reduce their work commitment and to identify the factors that
      influence such intentions. METHODS: An exploratory study using a cross-sectional
      survey design. Data were collected in 2014-2015 via an e-survey of 2,910 RNs in
      New Zealand. Data were analysed by regression. RESULTS: We found that due to
      "burnout" and low "work engagement", both of which are strongly affected by
      workload and work-life interference, 22.6% of the RNs surveyed plan to leave work
      altogether and a further 32% plan to reduce their workforce participation when
      their financial situations improve. CONCLUSIONS: The findings justify the urgent
      cooperative development, implementation and evaluation of a comprehensive suite
      of RN 'retention' measures involving national nursing organisations, the RN
      regulator and health system employers and funders.

PMID- 30200987
TI  - IgG subclass responses to excreted-secreted antigens of Plasmodium falciparum in
      a low-transmission malaria area of the Peruvian Amazon.
AB  - BACKGROUND: Malaria in Peru is concentrated in the Amazon region, especially in
      Loreto, and transmission is focused in rural and peri-urban communities. The
      government has approved a malaria elimination plan with a community approach and
      seeks to reduce the risk of transmission through preventive interventions, but
      asymptomatic and low-parasite-density infections are challenges for disease
      control and elimination. IgG antibodies play a critical role in combating
      infection through their ability to reduce parasitaemia and clinical symptoms. In
      particular, IgG subclasses have important roles in controlling malaria disease
      and may provide new insight into the development of malaria control strategies
      and understanding of malaria transmission. Through the use of excreted-secreted
      antigens from Plasmodium falciparum, were evaluated the responses of the four IgG
      subclasses in symptomatic and asymptomatic malarial infections. RESULTS: Higher
      levels of whole IgG were observed in asymptomatic carriers (P < 0.05). IgG3 and
      IgG1 were the most prevalent subclasses and did not show differences in their
      antibody levels in either type of carrier. All symptomatic carriers were positive
      for IgG4, and the presence of IgG3 and IgG2 were correlated with protection
      against parasitaemia. IgG2 showed lower prevalence and antibody titers in
      comparison to other subclasses. CONCLUSIONS: This is the first study that
      characterizes the IgG subclass response in the Peruvian Amazon, and these results
      show that even in populations from regions with low malaria transmission, a
      certain degree of naturally acquired immunity can develop when the right antibody
      subclasses are produced. This provides important insight into the potential
      mechanisms regulating protective immunity.

PMID- 30200989
TI  - Midlife development of type 2 diabetes and hypertension in women by history of
      hypertensive disorders of pregnancy.
AB  - BACKGROUND: Women with history of hypertensive disorders of pregnancy (HDP) are
      at increased risk of early onset cardiovascular disease and type 2 diabetes
      (T2D). We aimed to investigate the extent to which HDP is also associated with
      midlife development of T2D and hypertension above and beyond established risk
      factors. METHODS: We included parous women who attended population-based
      structured clinical visits at age 50 and 60 years in Sweden 1991-2013 (N = 6587).
      Women with prior diabetes mellitus, stroke, or ischemic heart disease at age 50
      years were excluded. Data on reproductive history were collected from registries.
      To study the association between history of HDP and the between-visits
      development of T2D, hypertension, and clinical risk factors of cardiometabolic
      disease (body mass index (BMI), blood pressure, and total cholesterol), we
      utilized multivariable adjusted regression models (logistic, log binomial, and
      linear regression, respectively). Models included data on outcome risk factors at
      age 50 years, e.g. BMI, 75 g 2 h oral glucose tolerance test result, and mean
      arterial pressure, respectively. RESULTS: Between ages 50 and 60 years, 5.8% of
      initially disease-free women developed T2D and 31.6% developed hypertension.
      History of HDP was associated with increased risk of developing T2D between age
      50 and 60 years even when adjusting for risk factors, including BMI, at age 50
      years (odds ratio (OR) 1.96, 95% confidence interval (CI) 1.29-2.98). By
      contrast, the higher risk of developing hypertension observed in women with
      history of HDP (relative risk (RR) 1.47, 95% CI 1.22-1.78) was attenuated when
      adjusted for risk factors (RR 1.09, 95% CI 0.94-1.25). Participants with a
      history of HDP had higher mean BMI and blood pressure at age 50 years, with
      levels roughly corresponding to those observed at age 60 years in unaffected
      women. CONCLUSIONS: Women with history of HDP are not only at higher risk of
      cardiometabolic disease during their reproductive years, but HDP is also
      associated with midlife T2D development above and beyond established risk
      factors.

PMID- 30200990
TI  - Changes in diet through adolescence and early adulthood: longitudinal
      trajectories and association with key life transitions.
AB  - BACKGROUND: Early adulthood is a period associated with poor diet and rapid
      weight gain. This is also an age of transition, including environmental, social
      and lifestyle changes which may be associated with changes in diet. We assess
      longitudinal associations between four early adulthood life transitions (leaving
      home, leaving education, entering employment, and cohabitation) and changes in
      consumption of fruit, vegetables, confectionery and sugar-sweetened beverages
      (SSBs). METHODS: Participants (n = 1100) from the Norwegian Longitudinal Health
      Behaviour Study, reported data on diet and life transitions on up to eight
      occasions from age 14 to age 30. Diet data were self-reported in response to
      questions on intake of fruit, vegetables, confectionery and sugar-sweetened
      beverages. Growth models were developed to describe changing intake of each of
      the four diet indicators with age. Fixed-effects regression models assessed
      associations between the four life transitions and within-individual changes in
      diet indicators, with adjustment for the remaining transitions and parenthood.
      RESULTS: Diet indicators showed quadratic trajectories with age: fruit and
      vegetable intakes declined from age 14 to ages 23 and 21 respectively, before
      increasing to age 30. SSB and confectionery intakes increased to age 18, before
      subsequently decreasing. Leaving the parental home was associated with a decrease
      in fruit intake of - 0.54 times/week (95% confidence interval (95%CI): -0.87;
      0.22) and vegetable intake of - 0.43 times/week (95%CI: -0.70;-0.15). Leaving
      education was associated with increases in confectionery (0.33 times/week (95%CI:
      0.04;0.62)) and SSB intakes (0.49 times/week (95%CI: 0.10;0.87). CONCLUSIONS:
      Leaving home and leaving education are associated with negative changes in diet
      and may present opportunities for effective diet and obesity intervention.
      Further study of these transitions is needed to understand the mechanisms
      mediating associations between life transitions and changes in diet.

PMID- 30200991
TI  - Evaluation of a fentanyl drug checking service for clients of a supervised
      injection facility, Vancouver, Canada.
AB  - BACKGROUND: British Columbia, Canada, is experiencing a public health emergency
      related to opioid overdoses driven by consumption of street drugs contaminated
      with illicitly manufactured fentanyl. This cross-sectional study evaluates a drug
      checking intervention for the clients of a supervised injection facility (SIF) in
      Vancouver. METHODS: Insite is a facility offering supervised injection services
      in Vancouver's Downtown East Side, a community with high levels of injection drug
      use and associated harms, including overdose deaths. During July 7, 2016, to June
      21, 2017, Insite clients were offered an opportunity to check their drugs for
      fentanyl using a test strip designed to test urine for fentanyl. Results of the
      drug check were recorded along with information including the substance checked,
      whether the client intended to dispose of the drug or reduce the dose and whether
      they experienced an overdose. Logistic regression models were constructed to
      assess the associations between drug checking results and dose reduction or drug
      disposal. Crude odds ratios (OR) and 95% confidence intervals (CI) were reported.
      RESULTS: About 1% of the visits to Insite during the study resulted in a drug
      check. Out of 1411 drug checks conducted by clients, 1121 (79.8%) were positive
      for fentanyl. Although most tests were conducted post-consumption, following a
      positive pre-consumption drug check, 36.3% (n = 142) of participants reported
      planning to reduce their drug dose while only 11.4% (n = 50) planned to dispose
      of their drug. While the odds of intended dose reduction among those with a
      positive drug check was significantly higher than those with a negative result
      (OR = 9.36; 95% CI 4.25-20.65), no association was observed between drug check
      results and intended drug disposal (OR = 1.60; 95% CI 0.79-3.26). Among all
      participants, intended dose reduction was associated with significantly lower
      odds of overdose (OR = 0.41; 95% CI 0.18-0.89). CONCLUSIONS: Although only a
      small proportion of visits resulted in a drug check, a high proportion (~ 80%) of
      the drugs checked were contaminated with fentanyl. Drug checking at harm
      reduction facilities such as SIFs might be a feasible intervention that could
      contribute to preventing overdoses in the context of the current overdose
      emergency.

PMID- 30200992
TI  - Quality of life among caregivers of sickle cell disease patients: a cross
      sectional study.
AB  - PURPOSE: To assess the quality of life (QoL) of caregivers of children with
      sickle cell disease (SCD) and to determine the risk factors associated with poor
      QoL. METHOD: A cross sectional study was conducted between 01 and 30 June 2015,
      in a tertiary care center in western Saudi Arabia to assess various dimensions of
      QoL by using TNO-AZL Questionnaire for Adult's Health-related Quality of Life
      (TAAQOL). A total 164 adult caregivers (aged 16 years or more) of children with
      SCD, who were regularly visiting the department were enrolled (refusal rate =
      61.6%). The questionnaire scores were transformed into 0-100 scale; with higher
      scores indicating less difficulty and better QoL Demographic, socioeconomic data
      and a satisfaction questionnaire regarding participants' lifestyle were collected
      and analyzed as risk factors for impaired QoL, by comparing different QoL
      dimensions' scores using independent t-test, Oneway ANOVA, or linear regression,
      as appropriate. RESULTS: Sixty-three caregivers were included; 79.4% were
      mothers, age range 21-71 years, 64.5% were from low social class receiving
      insufficient support and financial needs were unmet for considerable number of
      families. Analysis of QoL using TAAQOL showed that emotions (median [75th
      centile] = 44.44 [66.67] for negative and 61.11 [72.22] for positive emotions),
      sleep quality (66.67 [91.67]) and sexual life (50.00 [83.33]) were the most
      affected dimensions. Professional achievement (91.67 [100]), cognitive skills
      (83.33 [100]), and social contact (100 [100]) were relatively preserved. Negative
      emotions were more marked in mothers and mostly predicted by satisfaction with
      social relations notably with partner (B = 3.14, p = 0.016), friends (B = 2.51, p
      = 0.015) and relatives (B = 2.69, p = 0.016). Positive emotions were predicted by
      the levels of satisfaction of the caregiver with his/her health (B = 2.56, p =
      0.001), job achievement (B = 4.54, p = 0.001), living conditions (B = 2.60, p =
      0.034) and the condition of the diseased child (B = 2.55, p = 0.011). A strong
      correlation was found between sleep quality and cognitive skills. CONCLUSION:
      There are notable financial and emotional burdens on the caregivers of children
      with SCD affecting various aspects of their QoL, which are likely to be impacted
      by the individual levels of social and professional achievement. Physicians and
      health authorities should give particular attention to the QoL of caregivers and
      families of children with SCD, to help them cope up with the disease and overcome
      its related psychological and financial impacts.

PMID- 30200993
TI  - About feeding children: factor structure and internal reliability of a survey to
      assess mealtime strategies and beliefs of early childhood education teachers.
AB  - BACKGROUND: Children spend a substantial amount of time in early care and
      education (ECE) settings and may eat a majority of their diet in this setting.
      While there are several instruments focused on measuring factors of the ECE
      environment that may influence diet and weight outcomes, there are few
      comprehensive, valid, and reliable measures for collecting self-report of ECE
      providers' feeding practices. The purpose of this study was to establish the
      factor structure and internal reliability of a survey developed to measure
      practices and beliefs of ECE providers relative to feeding children. METHODS:
      Licensed ECE centers from CA, CO, ID and NV were included in this cross-sectional
      survey study. The sample was stratified by states and census regions to yield
      equal numbers of centers from each category. The total sample distribution
      included 1600 randomly selected centers and up to 8000 staff members (who
      represented teachers, aides, assistants, or cooks); 1178 surveys were completed.
      We conducted an exploratory, unrestricted factor analysis as well as parallel
      analyses to inform the number of factors to be extracted. RESULTS: Factors within
      Structural Mealtime Strategies included Adult Control of Foods Consumed (Kuder
      Richardson [KR] = 0.67), Bribing with Sweet Foods (KR = 0.70), and Supportive
      Adult Roles at Mealtime (KR = 0.55). Factors in Verbal Mealtime Strategies
      included Supporting Children's Eating Self-regulation (KR =0.61), Pressure to Eat
      (KR = 0.58), and Social Comparisons (KR = 0.59). Beliefs about Mealtime factors
      were Autonomy Promoting (alpha = 0.64), Coercive Beliefs (alpha = 0.77), and
      Concern-Based Control (alpha = 0.60). CONCLUSIONS: The AFC Strategies and Beliefs
      Survey provides a promising self-report instrument with a strong factor structure
      consistent with the extant literature to measure practices and beliefs related to
      feeding and mealtimes in the ECE setting. Feeding young children in group
      settings differs in many ways from feeding in a family setting; hence it is
      important that measures such as the AFC Strategies and Beliefs Survey capture
      unique aspects of the ECE feeding environment.

PMID- 30200994
TI  - TAP: a targeted clinical genomics pipeline for detecting transcript variants
      using RNA-seq data.
AB  - BACKGROUND: RNA-seq is a powerful and cost-effective technology for molecular
      diagnostics of cancer and other diseases, and it can reach its full potential
      when coupled with validated clinical-grade informatics tools. Despite recent
      advances in long-read sequencing, transcriptome assembly of short reads remains a
      useful and cost-effective methodology for unveiling transcript-level
      rearrangements and novel isoforms. One of the major concerns for adopting the
      proven de novo assembly approach for RNA-seq data in clinical settings has been
      the analysis turnaround time. To address this concern, we have developed a
      targeted approach to expedite assembly and analysis of RNA-seq data. RESULTS:
      Here we present our Targeted Assembly Pipeline (TAP), which consists of four
      stages: 1) alignment-free gene-level classification of RNA-seq reads using
      BioBloomTools, 2) de novo assembly of individual targets using Trans-ABySS, 3)
      alignment of assembled contigs to the reference genome and transcriptome with
      GMAP and BWA and 4) structural and splicing variant detection using PAVFinder. We
      show that PAVFinder is a robust gene fusion detection tool when compared to
      established methods such as Tophat-Fusion and deFuse on simulated data of 448
      events. Using the Leucegene acute myeloid leukemia (AML) RNA-seq data and a set
      of 580 COSMIC target genes, TAP identified a wide range of hallmark molecular
      anomalies including gene fusions, tandem duplications, insertions and deletions
      in agreement with published literature results. Moreover, also in this dataset,
      TAP captured AML-specific splicing variants such as skipped exons and novel
      splice sites reported in studies elsewhere. Running time of TAP on 100-150
      million read pairs and a 580-gene set is one to 2 hours on a 48-core machine.
      CONCLUSIONS: We demonstrated that TAP is a fast and robust RNA-seq variant
      detection pipeline that is potentially amenable to clinical applications. TAP is
      available at http://www.bcgsc.ca/platform/bioinfo/software/pavfinder.

PMID- 30200995
TI  - Progressive pseudorheumatoid dysplasia with new-found gene mutation of Wntl
      inducible signaling pathway protein 3.
AB  - BACKGROUND: As one kind of osteochondrodysplasia, progressive pseudorheumatoid
      dysplasia (PPD) is also known as spondyloepiphyseal dysplasia tarda with
      progressive arthropathy or arthropathy progressive pseudorheumatoid of childhood.
      PPD is a very rare disease, especially in China, and has an estimated prevalence
      of 1/1000000 due to lacking definite prevalence survey. It is an autosomal
      recessive disorder caused by gene mutation of Wntl inducible signaling pathway
      protein 3 (WISP3). Its basic pathological change is persistent degeneration and
      loss of articular cartilage in multiple joints. Its clinical appearances include
      bone enlargement, platyspondyly, irregular endplate, secondary osteoarthritis,
      extensive osteoporosis, joint rigidity and function loss. Clinical diagnosis of
      PPD is made based on clinical appearance and imaging examinations, whereas its
      definite diagnosis depends on gene sequencing. PPD has no severe effect on life
      span, but causes high disability rate and very poor prognosis. There are only
      case reports with limited information in China. CASE PRESENTATION: One female
      patient was diagnosed as PPD and secondary osteoarthritis. She had typical
      clinical appearance and imaging examinations, and received individualized
      therapeutic regimens. She had a gene mutation (c.72delT, p.T24TfsX4) of WISP3.
      This gene mutation has not been reported by previous literatures and included in
      Single Nucleotide Polymorphism Database. CONCLUSIONS: As the first time, this
      paper reported a patient with PPD caused by new-found gene mutation (c.72delT,
      p.T24TfsX4) of WISP3.

PMID- 30200997
TI  - alpha-Synuclein disrupts the anti-inflammatory role of Drd2 via interfering beta
      arrestin2-TAB1 interaction in astrocytes.
AB  - BACKGROUND: alpha-Synuclein (alpha-Syn)-induced neuroinflammation plays a crucial
      role in the pathogenesis of Parkinson's disease (PD). Dopamine D2 receptor (Drd2)
      has been regarded as a potential anti-inflammatory target in the therapy of
      neurodegenerative diseases. However, the effect of astrocytic Drd2 in alpha-Syn
      induced neuroinflammation remains unclear. METHODS: The effect of Drd2 on
      neuroinflammation was examined in mouse primary astrocyte in vitro and A53T
      transgenic mice in vivo. The inflammatory responses of astrocyte were detected
      using immunofluorescence, ELISA, and qRT-PCR. The details of molecular mechanism
      were assessed using Western blotting and protein-protein interaction assays.
      RESULTS: We showed that the selective Drd2 agonist quinpirole suppressed
      inflammation in the midbrain of wild-type mice, but not in alpha-Syn
      overexpressed mice. We also found that Drd2 agonists significantly alleviated LPS
      induced inflammatory response in astrocytes, but failed to suppress alpha-Syn
      induced inflammatory response. The anti-inflammation effect of Drd2 was dependent
      on beta-arrestin2-mediated signaling, but not classical G protein pathway. alpha
      Syn reduced the expression of beta-arrestin2 in astrocytes. Increased the beta
      arrestin2 expression restored in the anti-inflammation of Drd2 in alpha-Syn
      induced inflammation. Furthermore, we demonstrated that alpha-Syn disrupted the
      anti-inflammation of Drd2 via inhibiting the association of beta-arrestin2 with
      transforming growth factor-beta-activated kinase 1 (TAK1)-binding protein 1
      (TAB1) and promoting TAK1-TAB1 interaction in astrocytes. CONCLUSIONS: Our study
      illustrates that astrocytic Drd2 inhibits neuroinflammation through a beta
      arrestin2-dependent mechanism and provides a new strategy for treatment of PD.
      Our findings also reveal that alpha-Syn disrupts the function of beta-arrestin2
      and inflammatory pathways in the pathogenesis of PD.

PMID- 30200996
TI  - The human microglial HMC3 cell line: where do we stand? A systematic literature
      review.
AB  - Microglia, unique myeloid cells residing in the brain parenchyma, represent the
      first line of immune defense within the central nervous system. In addition to
      their immune functions, microglial cells play an important role in other cerebral
      processes, including the regulation of synaptic architecture and neurogenesis.
      Chronic microglial activation is regarded as detrimental, and it is considered a
      pathogenic mechanism common to several neurological disorders. Microglial
      activation and function have been extensively studied in rodent experimental
      models, whereas the characterization of human cells has been limited due to the
      restricted availability of primary sources of human microglia. To overcome this
      problem, human immortalized microglial cell lines have been developed. The human
      microglial clone 3 cell line, HMC3, was established in 1995, through SV40
      dependent immortalization of human embryonic microglial cells. It has been
      recently authenticated by the American Type Culture Collection (ATCC(r)) and
      distributed under the name of HMC3 (ATCC(r)CRL-3304). The HMC3 cells have been
      used in six research studies, two of which also indicated by ATCC(r) as reference
      articles. However, a more accurate literature revision suggests that clone 3 was
      initially distributed under the name of CHME3. In this regard, several studies
      have been published, thus contributing to a more extensive characterization of
      this cell line. Remarkably, the same cell line has been used in different
      laboratories with other denominations, i.e., CHME-5 cells and C13-NJ cells. In
      view of the fact that "being now authenticated by ATCC(r)" may imply a wider
      distribution of the cells, we aimed at reviewing data obtained with the human
      microglia cell line clone 3, making the readers aware of this complicated
      nomenclature. In addition, we also included original data, generated in our
      laboratory with the HMC3 (ATCC(r)CRL-3304) cells, providing information on the
      current state of the culture together with supplementary details on the culturing
      procedures to obtain and maintain viable cells.

PMID- 30200998
TI  - Adolescents, parents and teachers' perceptions of risk and protective factors of
      substance use in Moroccan adolescents: a qualitative study.
AB  - BACKGROUND: Substance use in adolescents is a global public health concern that
      continues to draw attention from academics, policy experts, and government
      officials. In Morocco, few studies have investigated the influencing factors of
      substance use in adolescents. Here, we aimed to fill this gap and to better
      understand factors that protect or influence substance use in adolescents.
      METHODS: We conducted a qualitative study using focus group discussions. The semi
      structured interview guides were based on the socio-ecological model as a
      theoretical framework to explore perceptions of students, parents, and teachers
      regarding substance use risks and protective factors in adolescents. Data from
      each group were audio-recorded, transcribed, and analyzed using thematic
      analysis. RESULTS: From May to July 2016, 17 focus group discussions were
      conducted at two middle schools in Taza city, Morocco, which included 8 groups of
      7 adolescents (28 boys and 28 girls) aged 14 to 16 years, 5 groups of parents (5
      females and 21 males), and 4 groups of teachers (13 males and 5 females).
      Thematic analysis resulted in six common themes that represented the most salient
      perceived risk and protective factors regarding substance use among adolescents:
      perceived benefits of substance use, awareness and beliefs, family influence,
      peer influence, easy accessibility of substances, and social norms. CONCLUSIONS:
      Our results demonstrate that multilevel prevention programs in adolescents should
      address influencing factors from the individual to the societal level, including
      social norms and the government's policy toward substance use. Health education
      programs included as part of the school curriculum can contribute to promoting
      awareness and reducing risky behaviors of Moroccan adolescents.

PMID- 30201000
TI  - Peripheral measurements of venous oxygen saturation and lactate as a less
      invasive alternative for hemodynamic monitoring.
AB  - BACKGROUND: Peripheral measurement of venous oxygen saturation and lactate is a
      less invasive alternative to monitor tissue oxygenation as compared to
      measurements from a central venous catheter. However, there is a lack of evidence
      to support the use of peripheral measurements. In this study, we investigated the
      agreement between central and peripheral venous oxygen saturation and lactate.
      METHODS: We conducted a prospective observational study including 115 patients
      who underwent elective cardiac surgery between April and May 2015 at
      Rigshospitalet, Copenhagen, Denmark. Measurements were obtained simultaneously at
      induction of anaesthesia, upon arrival in the ICU and 3-4 h postoperatively. Bias
      and trending ability was identified using Bland-Altman analysis and a four
      quadrant plot. RESULTS: Bias was 13.37% for venous oxygen saturation
      preoperatively (95% CI: 11.52-15.22, LoA: +/-19.10, PE: 22.08%), 11.29% at
      arrival to the ICU (95% CI: 8.81-13.77, LoA: +/-25.10, PE: 32.39%) and 16.49% at
      3-4 h postoperatively (95% CI: 14.16-18.82, LoA: +/-21.20, PE: 26.82%). A four
      quadrant plot demonstrated an 89% concordance. Central and peripheral lactate
      showed a bias of 0.14 mmol/L preoperatively (95% CI: 0.11-0.17, LoA: +/-0.30, PE:
      32.08%), 0.16 mmol/L at arrival to ICU (95% CI: 0.09-0.23, LoA: +/-0.70, PE:
      38.88%) and 0.23 mmol/L at 3-4 h postoperatively (95% CI: 0.11-0.35, LoA: +/
      0.50, 25.18%). DISCUSSION: Measurements of peripheral oxygen saturation and
      lactate may be valuable in an emergency setting, avoiding unnecessary and time
      consuming application of a CVC. CONCLUSION: We found a high bias but an
      acceptable trending ability between central and peripheral venous oxygenation.
      Central and peripheral lactate had excellent agreement. Further studies are
      necessary to validate the use of peripheral venous samples to identify patients
      at risk of impaired tissue oxygenation.

PMID- 30200999
TI  - Endothelial cells promote metastasis of prostate cancer by enhancing autophagy.
AB  - BACKGROUND: Prostate cancer is one of the most common malignancies. Increasing
      evidence suggested that endothelial cells may contribute to prostate cancer
      progression and metastasis. Most recently, autophagy has been proposed to plays a
      significant role in tumorigenesis and metastasis. Also, it is reported that
      downregulation of androgen receptor (AR) induces autophagy in prostate cancer
      cells. However, the underlying mechanisms remain unclear. Here, we aim to explore
      the role and mechanisms of endothelial cell in prostate cancer progression.
      METHODS: The coculture system was established to test the effect of endothelial
      cells on prostate cancer cells. We performed antibody array and ELISA were used
      to profile the cytokine expression pattern of endothelial cells in supernatant.
      Western blot and RT-PCR were used to determine the mechanism by endothelial cells
      to promote invasion ability of prostate cancer cells. Maraviroc and chloroquine
      were used to block the CCL5/CCR5 and autophagy pathway respectively. Orthotopic
      xenograft mouse models and drug treatment study were conducted to determine the
      role of endothelial cells in promoting metastatic potential in vivo. RESULTS: We
      use CPRC prostate cancer model and demonstrate that endothelial cells secrete
      large amount of CCL5 and induces autophagy by suppressing AR expression in
      prostate cancer cell lines. Consequently, elevated autophagy accelerates focal
      adhesions proteins disassembly and promoted prostate cancer invasion. Inhibition
      of both CCL5/CCR5 signaling and autophagy significantly reduces metastasis in
      vivo. CONCLUSIONS: Together, our data establish the function for endothelial
      cells in tumor metastasis and propose new drug target for mCRPC.

PMID- 30201001
TI  - Persistent megalocystic ovaries after ovarian hyperstimulation syndrome in a
      postpartum patient with polycystic ovarian syndrome: a case report.
AB  - BACKGROUND: Ovary enlargement is common in controlled ovarian stimulation, which
      could continue several months during a successful pregnancy. However, persistent
      megalocystic ovaries 3 years after ovarian hyperstimulation syndrome (OHSS) were
      rare. Here we will present you the case and treatment as well as discuss the
      probable etiology. CASE PRESENTATION: A 34-year-old woman with polycystic ovarian
      syndrome (PCOS) and a history of infertility presented to the Department of
      Obstetrics and Gynecology at Peking Union Medical College Hospital with abdominal
      pain and persistently enlarged ovaries 36 months after OHSS. Enlarged ovaries
      were evaluated with ultrasonography and serum tests. Diagnostic laparoscopic
      surgery with detorsion and drainage followed by GnRHa treatment was performed.
      Symptoms and ovarian size evaluated by vaginal ultrasound were the main outcome
      measures. The patient was discharged from the hospital 5 days after surgery
      without any remarkable complications. Both ovaries recovered to almost normal
      after a monthly injection of GnRHa for 3 months. CONCLUSIONS: Ovarian enlargement
      may persist for a long time in patients with severe OHSS even after sex hormone
      levels and ovarian functions return to normal. Long term follow-up is necessary
      and ovarian torsion should be suspected when accompanied by abdominal pain.
      Acupuncture plus GnRHa treatment may be an effective way for these cases.

PMID- 30201003
TI  - A health state utility valuation study to assess the impact of treatment mode of
      administration in Gaucher disease.
AB  - BACKGROUND: This study aimed to obtain UK societal-based utility values for
      health states related to treatment mode of administration using Gaucher disease
      as the background condition. METHODS: A review of relevant literature and expert
      clinical input informed the development of five health states characterising the
      impact of Gaucher disease and its management on patients' lives. A base-state
      characterising the "controlled disease" was developed as well as four subsequent
      health states which varied in description of the method (intravenous versus oral)
      and frequency of treatment administration. Health state utilities were obtained
      using the time trade-off (TTO) method via face-to-face interviews with 100
      members from the UK general population. Before the valuation exercise,
      participants provided informed consent, completed a demographic form and the EQ
      5D, and ranked the health states from best to worst on a 0-100 visual analogue
      scale (VAS). RESULTS: Mean age of the participants (n = 100) was 35 years and 66%
      were female. Participants reported high EQ-5D VAS (86.1) and index scores (0.95)
      indicating very good health status. The "controlled disease" state had the
      highest mean TTO-derived utility value (0.89). There was only a marginal
      reduction in utility for the generic state for "Oral treatment" (0.85), while the
      reduction was more pronounced for the generic state for "Intravenous treatment"
      (0.73). CONCLUSIONS: The findings suggest that the avoidance of the need for
      intravenous treatment administration is associated with a notable positive
      increase in health-related quality of life. Patient benefit arising from less
      invasive treatment could be an important consideration when undertaking economic
      evaluation of future therapies for Gaucher disease.

PMID- 30201002
TI  - FBP1 loss contributes to BET inhibitors resistance by undermining c-Myc
      expression in pancreatic ductal adenocarcinoma.
AB  - BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal
      tumor types worldwide. BET inhibitors display anti-tumor activity in pancreatic
      cancer, however the cells often develop resistance after a long-term treatment
      and the underlying molecular basis is not fully understood. METHODS: Drug
      screening assay in Fructose-1, 6-biphosphatase (FBP1) knockdown or overexpressing
      pancreatic cancer cells was performed. Tumor cell motility, FBP1 protein and mRNA
      changes were investigated after BET inhibitors treatment. The interaction between
      TRIM28 and FBP1 after BET inhibitors treatment was examined by Co
      immunoprecipitation (IP) and GST pull-down. The relationship between FBP1 and c
      Myc was examined by western blot, RT-qPCR and immunohistochemistry (IHC).
      RESULTS: The expression of FBP1 protein increased the sensitivity of pancreatic
      cancer cells to JQ1. Furthermore, we showed that JQ1 stabilized FBP1 protein
      level by disrupting the interaction between FBP1 and TRIM28 in pancreatic cancer
      cells. Moreover, we demonstrated that FBP1 promoted c-Myc degradation through
      disrupting the ERK-c-Myc axis. CONCLUSIONS: FBP1 modulates the sensitivity of
      pancreatic cancer cells to BET inhibitors by decreasing the expression of c-Myc.
      These findings highlight FBP1 could be used as a therapeutic niche for patient
      tailored therapies.

PMID- 30201005
TI  - Survival benefit of re-irradiation in esophageal Cancer patients with
      Locoregional recurrence: a propensity score-matched analysis.
AB  - BACKGROUND: To investigate the treatment failure pattern and factors influencing
      locoregional recurrence of esophageal squamous cell carcinoma (ESCC) and examine
      patient survival with re-irradiation (re-RT) after primary radiotherapy. METHODS:
      We retrospectively analyzed 87 ESCC patients treated initially with radiotherapy.
      Failure patterns were classified into regional lymph node recurrence only (LN)
      and primary failure with/without regional lymph node recurrence (PF). Patients
      received either re-RT or other treatments (non-re-RT group). Baseline covariates
      were balanced by a propensity score model. Overall survival (OS) and toxicities
      were assessed as outcomes. RESULTS: The median follow-up time was 87 months.
      Thirty-nine patients received re-RT. Failure pattern and re-RT were independent
      prognostic factors for OS (P = 0.040 and 0.015) by Cox multivariate analysis. Re
      RT with concomitant chemotherapy showed no survival benefit over re-RT alone (P =
      0.70). No differences in characteristics were found between the groups by Chi
      square tests after propensity score matching. The Cox model showed that failure
      pattern and re-RT were prognostic factors with hazard ratios (HR) of 0.319 (P =
      0.025) and 0.375 (P = 0.002), respectively, in the matched cohort. Significant
      differences in OS were observed according to failure pattern (P = 0.004) and re
      RT (P < 0.001). In the re-RT and non-re-RT groups, 9.09% and 3.03% of patients
      experienced tracheoesophageal fistulas, and 15.15% and 3.03% of patients
      developed pericardial/pleural effusion, respectively (P > 0.05). The incidence of
      radiation pneumonitis was higher in the re-RT group (24.24% vs. 6.06%, P =
      0.039), but no cases of pneumonia-related death occurred. CONCLUSIONS: Re-RT
      improved long-term survival in patients with locoregional recurrent ESCC. Despite
      a high incidence of radiation pneumonitis, toxicities were tolerable.

PMID- 30201004
TI  - Maternal inhalation of carbon black nanoparticles induces neurodevelopmental
      changes in mouse offspring.
AB  - BACKGROUND: Engineered nanoparticles are smaller than 100 nm and designed to
      improve or creating even new physico-chemical properties. Consequently,
      toxicological properties of materials may change as size reaches the nm size
      range. We examined outcomes related to the central nervous system in the
      offspring following maternal inhalation exposure to nanosized carbon black
      particles (Printex 90). METHODS: Time-mated mice (NMRI) were exposed by
      inhalation, for 45 min/day to 0, 4.6 or 37 mg/m3 aerosolized carbon black on
      gestation days 4-18, i.e. for a total of 15 days. Outcomes included maternal lung
      inflammation (differential cell count in bronchoalveolar lavage fluid and Saa3
      mRNA expression in lung tissue), offspring neurohistopathology and behaviour in
      the open field test. RESULTS: Carbon black exposure did not cause lung
      inflammation in the exposed females, measured 11 or 28-29 days post-exposure.
      Glial fibrillary acidic protein (GFAP) expression levels were dose-dependently
      increased in astrocytes around blood vessels in the cerebral cortex and
      hippocampus in six weeks old offspring, indicative of reactive astrogliosis. Also
      enlarged lysosomal granules were observed in brain perivascular macrophages
      (PVMs) in the prenatally exposed offspring. The number of parvalbumin-positive
      interneurons and the expression levels of parvalbumin were decreased in the motor
      and prefrontal cortices at weaning and 120 days of age in the prenatally exposed
      offspring. In the open field test, behaviour was dose-dependently altered
      following maternal exposure to Printex 90, at 90 days of age. Prenatally exposed
      female offspring moved a longer total distance, and especially males spent
      significantly longer time in the central zone of the maze. In the offspring, the
      described effects were long-lasting as they were present at all time points
      investigated. CONCLUSION: The present study reports for the first time that
      maternal inhalation exposure to Printex 90 carbon black induced dose-dependent
      denaturation of PVM and reactive astrocytes, similarly to the findings observed
      following maternal exposure to Printex 90 by airway instillation. Of note, some
      of the observed effects have striking similarities with those observed in mouse
      models of neurodevelopmental disorders.

PMID- 30201006
TI  - Consensus statement on physical rehabilitation in children and adolescents with
      osteogenesis imperfecta.
AB  - On the occasion of the 13th International Conference on Osteogenesis imperfecta
      in August 2017 an expert panel was convened to develop an international consensus
      paper regarding physical rehabilitation in children and adolescents with
      Osteogenesis imperfecta. The experts were chosen based on their clinical
      experience with children with osteogenesis imperfecta and were identified by
      sending out questionnaires to specialized centers and patient organizations in 26
      different countries. The final expert-group included 16 representatives (12
      physiotherapists, two occupational therapists and two medical doctors) from 14
      countries. Within the framework of a collation of personal experiences and the
      results of a literature search, the participating physiotherapists, occupational
      therapists and medical doctors formulated 17 expert-statements on physical
      rehabilitation in patients aged 0-18 years with osteogenesis imperfecta.

PMID- 30201007
TI  - The satisfaction regarding handovers between ambulance and emergency department
      nurses: an observational study.
AB  - BACKGROUND: A thorough handover in the emergency department (ED) is of great
      importance for improving the quality and safety in the chain of care. The
      satisfaction of handover may reflect the quality of handover. Research to
      discover the variables influencing the satisfaction of handovers is scarce. The
      goal of this study was to determine the factors influencing the satisfaction
      regarding handovers from ambulance and ED nurses. METHODS: We performed a
      prospective observational study in the University Medical Center of Groningen.
      Data regarding prehospital-hospital handovers has been collected by observing
      handovers and assessing patient chart information. Data regarding the
      satisfaction has been collected with a questionnaire including a 5-point scale
      for the level of satisfaction. RESULTS: In total, 97 handovers were observed and
      97 ambulance nurses and 89 ED nurses completed the questionnaire. The
      satisfaction of ambulance nurses showed a negative correlation with the waiting
      time prior to handover (r = -.287, p = .004) and a positive correlation with the
      presence of a physician in the receiving team (r = .224, p = .028). The
      satisfaction of ED nurses showed a positive correlation with the use of the ABCDE
      (r = .288, p = .006) and AMPLE instrument (r = .208, p = .050). CONCLUSION: The
      satisfaction of ambulance and ED nurses as sender or receiver of the handover is
      determined by different factors. The satisfaction of ambulance nurses is mainly
      affected by the waiting time and presence of a physician, while the satisfaction
      of ED nurses is affected by the use of handover instruments and the completeness
      of medical information.

PMID- 30201009
TI  - "It's something that marks you": Abortion stigma after decriminalization in
      Uruguay.
AB  - BACKGROUND: Abortion stigma is experienced by women seeking abortion services and
      by abortion providers in a range of legal contexts, including Uruguay, where
      abortion was decriminalized up to 12 weeks gestation in 2012. This paper analyzes
      opinions and attitudes of both abortion clients and health professionals
      approximately two years following decriminalization and assesses how abortion
      stigma manifests among these individuals and in institutions that provide care.
      METHODS: In 2014, we conducted twenty in-depth, semi-structured interviews with
      abortion clients (n = 10) and health care professionals (n = 10) in public and
      private facilities across Uruguay's health system. Interviews were recorded,
      transcribed, and then coded for thematic analysis. RESULTS: We find that both
      clients and health professionals express widespread satisfaction with the
      implementation of the new law. However, there exist critical points in the
      service where stigmatizing ideas and attitudes continue to be reproduced, such as
      the required five-day waiting period and in interactions with hospital staff who
      do not support access to the service. We also document the prevalence of
      stigmatizing ideas around abortion that continue to circulate outside the
      clinical setting. CONCLUSION: Despite the benefits of decriminalization, abortion
      clients and health professionals still experience abortion stigma.

PMID- 30201008
TI  - Next-generation sequencing analyses of the emergence and maintenance of mutations
      in CTL epitopes in HIV controllers with differential viremia control.
AB  - BACKGROUND: Despite the low level of viral replication in HIV controllers (HICs),
      studies have reported viral mutations related to escape from cytotoxic T
      lymphocyte (CTL) response in HIV-1 plasma sequences. Thus, evaluating the
      dynamics of the emergence of CTL-escape mutants in HICs reservoirs is important
      for understanding viremia control. To analyze the HIV-1 mutational profile and
      dynamics of CTL-escape mutants in HICs, we selected 11 long-term non-progressor
      individuals and divided them into the following groups: (1) viremic controllers
      (VCs; n = 5) and (2) elite controllers (ECs; n = 6). For each individual, we used
      HIV-1 proviral DNA from PBMCs related to earliest (VE) and latest (VL) visits to
      obtain gag and nef sequences using the Illumina HiSeq system. The consensus of
      each mapped gene was used to assess viral divergence, and next-generation
      sequencing data were employed to identify SNPs and variations within and flanking
      CTL epitopes. RESULTS: Divergence analysis showed higher values for nef compared
      to gag among the HICs. EC and VC groups showed similar divergence rates for both
      genes. Analysis of the number of SNPs showed that VCs present more variability in
      both genes. Synonymous/non-synonymous mutation ratios were < 1 for gag among ECs
      and for nef among ECs and VCs, exhibiting a predominance of non-synonymous
      mutations. Such mutations were observed in regions encoding CTL-restricted
      epitopes in all individuals. All ECs presented non-synonymous mutations in CTL
      epitopes but generally at low frequency (< 1%); all VCs showed a high number of
      mutations, with significant frequency changes between VE and VL visits. A higher
      frequency of internal mutations was observed for gag epitopes, with significant
      changes across visits compared to Nef epitopes, indicating a pattern associated
      with differential genetic pressure. CONCLUSIONS: The high genetic conservation of
      HIV-1 gag and nef among ECs indicates that the higher level of viremia control
      restricts the evolution of both genes. Although viral replication levels in HICs
      are low or undetectable, all individuals exhibited CTL epitope mutations in
      proviral gag and nef variants, indicating that potential CTL escape mutants are
      present in HIC reservoirs and that situations leading to a disequilibrium of the
      host-virus relationship can result in the spread of CTL-escape variants.

PMID- 30201011
TI  - Correction to: Goats in the city: prevalence of Giardia duodenalis and
      Cryptosporidium spp. in extensively reared goats in northern India.
AB  - In the original publication of this article [1] the supplementary file was
      missing two primers for the PCR reaction and the PCR conditions of Giardia and
      Cryptosporidium. In this correction article the updated additional file
      (Additional file 1) is available, in which the two primers are included.

PMID- 30201010
TI  - LncRNA SLCO4A1-AS1 facilitates growth and metastasis of colorectal cancer through
      beta-catenin-dependent Wnt pathway.
AB  - BACKGROUND: Emerging evidence has shown long noncoding RNAs (lncRNAs) exert
      important roles in colorectal cancer (CRC) tumorigenesis. However, most lncRNAs
      involved in this process remain undefined and the underlying molecular mechanisms
      mediated by lncRNAs are largely unknown. METHODS: An unbiased screening was used
      to identify novel lncRNAs involved in CRC according to an online-available data
      dataset. In situ hybridization (ISH) and qRT-PCR was used to detect lncRNA
      expression patterns. CCK8, colony formation, fluorescence activated cell sorter
      (FACS), transwell, xenograft nude mouse model and western blot assays were used
      to analyze the functions of SLCO4A1-AS1. RNA-pulldown, western blot, RNA
      fluorescence in situ hybridization (RNA-FISH) and electrophoretic mobility shift
      assay (EMSA) assays were utilized to explore the molecular mechanism of SLCO4A1
      AS1. RESULTS: LncRNA SLCO4A1-AS1 was significantly upregulated in CRC tissues and
      its overexpression was closely related with poor prognosis and tumor metastasis.
      By knocking down SLCO4A1-AS1, we found that SLCO4A1-AS1 promoted the
      proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) of
      CRC cells in vitro, as well as inhibited cell apoptosis. Moreover, SLCO4A1-AS1
      dramatically delayed tumor propagation in vivo. Mechanistically, SLCO4A1-AS1
      activates Wnt/beta-catenin signaling. SLCO4A1-AS1 enhanced the stability of beta
      catenin by impairing the interaction of beta-catenin with GSKbeta and inhibiting
      its phosphorylation. Finally, restoration of beta-catenin protein level rescued
      the proliferation, migration and invasion in SLCO4A1-AS1-depleted CRC cells.
      CONCLUSION: SLCO4A1-AS1 serves as an oncogenic role in CRC through activating
      Wnt/beta-catenin signaling pathway. And SLCO4A1-AS1 might be a useful biomarker
      for CRC diagnosis and prognosis.

PMID- 30201013
TI  - Blood volume measurement using cardiovascular magnetic resonance and ferumoxytol:
      preclinical validation.
AB  - BACKGROUND: The hallmark of heart failure is increased blood volume. Quantitative
      blood volume measures are not conveniently available and are not tested in heart
      failure management. We assess ferumoxytol, a marketed parenteral iron supplement
      having a long intravascular half-life, to measure the blood volume with
      cardiovascular magnetic resonance (CMR). METHODS: Swine were administered 0.7
      mg/kg ferumoxytol and blood pool T1 was measured repeatedly for an hour to
      characterize contrast agent extraction and subsequent effect on Vblood estimates.
      We compared CMR blood volume with a standard carbon monoxide rebreathing method.
      We then evaluated three abbreviated acquisition protocols for bias and precision.
      RESULTS: Mean plasma volume estimated by ferumoxytol was 61.9 +/- 4.3 ml/kg.
      After adjustment for hematocrit the resultant mean blood volume was 88.1 +/- 9.4
      ml/kg, which agreed with carbon monoxide measures (91.1 +/- 18.9 ml/kg). Repeated
      measurements yielded a coefficient of variation of 6.9%, and Bland-Altman
      repeatability coefficient of 14%. The blood volume estimates with abbreviated
      protocols yielded small biases (mean differences between 0.01-0.06 L) and strong
      correlations (r2 between 0.97-0.99) to the reference values indicating clinical
      feasibility. CONCLUSIONS: In this swine model, ferumoxytol CMR accurately
      measures plasma volume, and with correction for hematocrit, blood volume.
      Abbreviated protocols can be added to diagnostic CMR examination for heart
      failure within 8 min.

PMID- 30201014
TI  - Yellow nail syndrome with chylothorax after coronary artery bypass grafting.
AB  - BACKGROUND: Yellow nail syndrome is a rare condition considered secondary to
      functional anomalies of lymphatic drainage. Yellow nail syndrome is diagnosed
      through the triad of intrathoracic findings (30% being pleural effusions), nail
      discoloration, and lymphedema, with any two features sufficient for diagnosis. We
      report the second case of post-operative yellow nail syndrome. CASE PRESENTATION:
      After coronary artery bypass grafting, our patient presented with chylothorax on
      post-operative day 13 and yellow toenail discoloration on post-operative day 28,
      diagnosing yellow nail syndrome. Initial conservative management with pigtail
      catheter drainage and low-fat diet with medium-chain triglycerides reduced
      chylous drainage from 350 mL/day on post-operative day 14 to < 100 mL/day on post
      operative day 17. However, by post-operative day 18, drainage returned to 350
      mL/day that persisted despite attempts to readjust the catheter position,
      replacement of catheter with chest tube, and transition to total parenteral
      nutrition and octreotide while nil per os. Lymphangiogram on post-operative day
      32 did not identify the thoracic duct or cisterna chyli, precluding embolization.
      Talc and doxycycline pleurodeses performed on post-operative days 33 and 38,
      respectively, resolved his chylothorax and nail discoloration. CONCLUSIONS: Both
      yellow nail syndrome and chylothorax as a complication of coronary artery bypass
      grafting are rare entities. The proposed mechanism of post-operative chylothorax
      is iatrogenic injury to thoracic duct or collateral lymphatic vessels. Diagnosing
      yellow nail syndrome in patients with post-operative chylothorax (through co
      existing yellow nail discoloration and/or lymphedema) may suggest predisposition
      to impaired lymphatic drainage, portending a difficult recovery and potentially
      indicating need for surgical management.

PMID- 30201015
TI  - Comparing simultaneous integrated boost vs sequential boost in anal cancer
      patients: results of a retrospective observational study.
AB  - BACKGROUND: To evaluate clinical outcomes of simultaneous integrated boost (SIB) 
      intensity modulated radiotherapy (RT) in patients with non metastatic anal
      cancer compared to those of a set of patients treated with 3-dimensional
      conformal RT and sequential boost (SeqB). METHODS: A retrospective cohort of 190
      anal cancer patients treated at 3 academic centers with concurrent chemo-RT
      employing either SIB or SeqB was analysed. The SIB-group consisted of 87
      patients, treated with 2 cycles of Mitomycin (MMC) and 5-Fluorouracil (5FU) using
      SIB-IMRT delivering 42-45Gy/28-30 fractions to the elective pelvic lymph nodes
      and 50.4-54Gy/28-30fractions to the primary tumor and involved nodes, based on
      pre-treatment staging. The SeqB group comprised 103 patients, treated with MMC
      associated to either 5FU or Capecitabine concurrent to RT with 36 Gy/20 fractions
      to a single volume including gross tumor, clinical nodes and elective nodal
      volumes and a SeqB to primary tumor and involved nodes of 23.4 Gy/13 fractions.
      We compared colostomy-free survival (CFS), overall survival (OS) and the
      cumulative incidence of colostomy for each radiation modality. Cox proportional
      hazards model addressed factors influencing OS and CFS. RESULTS: Median follow up
      was 34 (range 9-102) and 31 months (range 2-101) in the SIB and SeqB groups. The
      1- and 2-year cumulative incidences of colostomy were 8.2% (95%CI:3.6-15.2) and
      15.0% (95%CI:8.1-23.9) in the SIB group and 13.9% (95%CI: 7.8-21.8) and 18.1%
      (95%CI:10.8-27.0) in the SeqB group. Two-year CFS and OS were 78.1% (95%CI:67.0
      85.8) and 87.5% (95%CI:77.3-93.3) in the SIB group and 73.5% (95%CI:62.6-81.7)
      and 85.4% (95%CI:75.5-91.6) in the SeqB, respectively. A Cox proportional hazards
      regression model highlighted an adjusted hazard ratio (AdjHR) of 1.18 (95%CI:
      0.67-2.09;p = 0.560), although AdjHR for the first 24 months was 0.95 (95%CI:
      0.49-1.84;p = 0.877) for the SIB approach. CONCLUSIONS: SIB-based RT provides
      similar clinical outcomes compared to SeqB-based in the treatment of patients
      affected with non metastatic anal cancer.

PMID- 30201012
TI  - DNA methylation footprints during soybean domestication and improvement.
AB  - BACKGROUND: In addition to genetic variation, epigenetic variation plays an
      important role in determining various biological processes. The importance of
      natural genetic variation to crop domestication and improvement has been widely
      investigated. However, the contribution of epigenetic variation in crop
      domestication at population level has rarely been explored. RESULTS: To
      understand the impact of epigenetics on crop domestication, we investigate the
      variation of DNA methylation during soybean domestication and improvement by
      whole-genome bisulfite sequencing of 45 soybean accessions, including wild
      soybeans, landraces, and cultivars. Through methylomic analysis, we identify 5412
      differentially methylated regions (DMRs). These DMRs exhibit characters distinct
      from those of genetically selected regions. In particular, they have
      significantly higher genetic diversity. Association analyses suggest only 22.54%
      of DMRs can be explained by local genetic variations. Intriguingly, genes in the
      DMRs that are not associated with any genetic variation are enriched in
      carbohydrate metabolism pathways. CONCLUSIONS: This study provides a valuable map
      of DNA methylation across diverse accessions and dissects the relationship
      between DNA methylation variation and genetic variation during soybean
      domestication, thus expanding our understanding of soybean domestication and
      improvement.

PMID- 30201016
TI  - Lightning accidents in the Austrian alps - a 10-year retrospective nationwide
      analysis.
AB  - BACKGROUND: Lightning strikes are rare but potentially lethal. The risk for
      suffering a lightning strike in a mountain environment is unknown. The aim of
      this nationwide study was to analyse all lightning accidents in the Austrian Alps
      from 2005 to 2015, to assess the circumstances of the accident, the injury
      pattern as well as the outcome. METHODS: From 2005 to 2015, data from the
      national Austrian Alpine Police database as well as the Clinical Information
      System of Innsbruck Medical University Hospital were searched for the keywords
      lightning injury, lightning strike, lightning as well as ICD-10 Code T75.0.
      Additionally, the archive data of Innsbruck Medical University Hospital was
      searched manually. RESULTS: The Austrian Alpine Police database, containing
      109.168 patients for the years 2005-2015, was screened for lightning accidents.
      Sixty-four patients had been hit by lightning in the Austrian Alps, 54 were male.
      Four persons died on scene; survival rate was 93.8%. Two deceased persons were
      hunters, who were killed by the same lightning strike. Sixty-three patients
      suffered a lightning strike while doing a recreational activity, mostly hiking (n
      = 55), a few hunting and only one doing occupational timberwork. Sixty-three
      patients suffered a lightning strike between June and August with nearly half
      (46.9%) of the accidents happening on a Saturday or Sunday, and mainly (95.3%)
      between 12:00 and 22:00 h. DISCUSSION: Persons who perform recreational outdoor
      and occupational activities in an alpine environment during summer and after noon
      incur a higher risk of sustaining a lightning strike. The primary risk group
      includes young male mountaineers and hunters. The mortality rate was low. TRIAL
      REGISTRATION: The study was approved by the Ethics Committee of the Medical
      University of Innsbruck (AN4757 315/4.4) and retrospectively registered with
      Clinical Trials NCT03405467 , January 19, 2018.

PMID- 30201017
TI  - Planning comparison of five automated treatment planning solutions for locally
      advanced head and neck cancer.
AB  - BACKGROUND: Automated treatment planning and/or optimization systems (ATPS) are
      in the process of broad clinical implementation aiming at reducing inter-planner
      variability, reducing the planning time allocated for the optimization process
      and improving plan quality. Five different ATPS used clinically were evaluated
      for advanced head and neck cancer (HNC). METHODS: Three radiation oncology
      departments compared 5 different ATPS: 1) Automatic Interactive Optimizer (AIO)
      in combination with RapidArc (in-house developed and Varian Medical Systems); 2)
      Auto-Planning (AP) (Philips Radiation Oncology Systems); 3) RapidPlan version
      13.6 (RP1) with HNC model from University Hospital A (Varian Medical Systems,
      Palo Alto, USA); 4) RapidPlan version 13.7 (RP2) combined with scripting for
      automated setup of fields with HNC model from University Hospital B; 5)
      Raystation multicriteria optimization algorithm version 5 (RS) (Laboratories AB,
      Stockholm, Sweden). Eight randomly selected HNC cases from institution A and 8
      from institution B were used. PTV coverage, mean and maximum dose to the organs
      at risk and effective planning time were compared. Ranking was done based on 3 Gy
      increments for the parallel organs. RESULTS: All planning systems achieved the
      hard dose constraints for the PTVs and serial organs for all patients. Overall,
      AP achieved the best ranking for the parallel organs followed by RS, AIO, RP2 and
      RP1. The oral cavity mean dose was the lowest for RS (31.3 +/- 17.6 Gy), followed
      by AP (33.8 +/- 17.8 Gy), RP1 (34.1 +/- 16.7 Gy), AIO (36.1 +/- 16.8 Gy) and RP2
      (36.3 +/- 16.2 Gy). The submandibular glands mean dose was 33.6 +/- 10.8 Gy (AP),
      35.2 +/- 8.4 Gy (AIO), 35.5 +/- 9.3 Gy (RP2), 36.9 +/- 7.6 Gy (RS) and 38.2 +/-
      7.0 Gy (RP1). The average effective planning working time was substantially
      different between the five ATPS (in minutes): < 2 +/- 1 for AIO and RP2, 5 +/- 1
      for AP, 15 +/- 2 for RP1 and 340 +/- 48 for RS, respectively. CONCLUSIONS: All
      ATPS were able to achieve all planning DVH constraints and the effective working
      time was kept bellow 20 min for each ATPS except for RS. For the parallel organs,
      AP performed the best, although the differences were small.

PMID- 30201018
TI  - How does the length of cardiopulmonary resuscitation affect brain damage in
      patients surviving cardiac arrest? A systematic review.
AB  - BACKGROUND: Brain injury can occur after cardiac arrest due to the effects of
      ischaemia and reperfusion. In serious cases this can lead to permanent
      disability. This risk must be considered when making decisions about terminating
      resuscitation. There are very specific rules for termination of resuscitation in
      the prehospital setting however a similar rule for resuscitation in hospital does
      not exist. The aim of this review was to explore the effects of duration of
      cardiopulmonary resuscitation on neurological outcome in survivors of both in
      hospital and out-of-hospital cardiac arrest achieving return of spontaneous
      circulation in hospital. METHODS: A systematic review was conducted. Five
      databases were searched in addition to hand searching the journals Resuscitation
      and Circulation and reference lists, quality of the selected studies was assessed
      and a narrative summary of the data presented. Studies reporting relevant
      outcomes were included if the participants were adults achieving return of
      spontaneous circulation in the hospital setting. Studies looking at additional
      interventions such as extracorporeal resuscitation and therapeutic hypothermia
      were not included. Case studies were excluded. The study period was from January
      2010 to March 2016. RESULTS: Seven cohort studies were included for review.
      Quality scores ranged from eight to 11 out of 12. Five of the studies found a
      significant association between shorter duration of resuscitation and favourable
      neurological outcome. CONCLUSIONS: There is generally a better neurological
      outcome with a shorter duration of CPR in survivors of cardiac arrest however a
      cut-off beyond which resuscitation is likely to lead to unfavourable outcome
      could not be determined and is unlikely to exist. The findings of this review
      could be considered by clinicians making decisions about terminating
      resuscitation. This review has highlighted many gaps in the knowledge where
      future research is needed; a validated and reliable measure of neurological
      outcome following cardiac arrest, more focused research on the effects of
      duration on neurological outcome and further research into the factors leading to
      brain damage in cardiac arrest.

PMID- 30201019
TI  - Inflammation-induced Gro1 triggers senescence in neuronal progenitors: effects of
      estradiol.
AB  - BACKGROUND: Inflammation has been proposed to contribute to the decline in adult
      hippocampal neurogenesis. Proinflammatory cytokines activate transcription of
      chemokine growth-regulated oncogene alpha (Gro1) in human and murine hippocampal
      neuronal progenitor cells (NPC). The goal of this study was to investigate the
      effects of Gro1 on hippocampal neurogenesis in the presence of inflammation.
      METHODS: Human hippocampal NPC were transfected with lentivirus expressing Gro1,
      and murine NPC and hippocampal neuronal HT-22 cells were treated with Gro1
      protein. A plasmid expressing mGro1 was electroporated in the hippocampus of
      newborn mice that were sacrificed 10 days later. Adult male and female mice were
      injected with lipopolysaccharide (LPS; 1 mg/kg, i.p in five daily injections) or
      normal saline. Adult male mice were implanted with pellets releasing 17-beta
      estradiol (E2; 2.5 mg/pellet, 41.666 MUg/day release) or placebo for 6 weeks and
      challenged with LPS or normal saline as above. In both experiments, mice were
      sacrificed 3 h after the last injection. Hippocampal markers of neurogenesis were
      assessed in vitro and in vivo by Western blot, real-time PCR, and
      immunohisto/cytochemistry. RESULTS: Gro1 induced premature senescence in NPC and
      HT-22 cells, activating senescence-associated beta-galactosidase and the cell
      cycle inhibitor p16 and suppressing neuroblast proliferation and expression of
      doublecortin (DCX) and neuron-specific class III beta-tubulin (Tuj-1), both
      neuroblast markers, while promoting proliferation of neural glial antigen 2 (Ng2)
      positive oligodendrocytes. Gro1 overexpression in the hippocampus of newborn mice
      resulted in decreased neuroblast development, as evidenced by decreased DCX
      expression and increased expression of platelet-derived growth factor alpha
      receptor (PDGFalphaR), a marker of oligodendrocyte precursors. In adult mice,
      Gro1 was induced in response to LPS treatment in male but not in female
      hippocampus, with a subsequent decrease in neurogenesis and activation of
      oligodendrocyte progenitors. No changes in neurogenesis were observed in females.
      Treatment with E2 blunted LPS-induced Gro1 in the male hippocampus. CONCLUSIONS:
      Inflammation-induced Gro1 triggers neuroblast senescence, thus suppressing new
      neuron development in the hippocampus. Sex-dependent differences in Gro1 response
      are attributed to estradiol, which blunts these changes, protecting the female
      hippocampus from the deleterious effects of inflammation-induced Gro1 on
      neurogenesis.

PMID- 30201021
TI  - Selective killing of circulating tumor cells prevents metastasis and extends
      survival.
AB  - Distant metastasis is initiated by circulating tumor cells (CTCs), which are
      considered to be a determining factor for the degree of metastasis and the
      survival of cancer patients. Although CTC-based diagnostic approaches are being
      rapidly developed, limited studies have proven the benefits of CTC elimination,
      with most studies providing only hypothetical inference because of the technical
      difficulty in examining the effects of CTC elimination in vivo. We modified
      photodynamic therapy to specifically eliminate green fluorescent protein (GFP)
      expressing CTCs and evaluated the therapeutic efficacy of CTC elimination. When
      circulating blood is illuminated with a blue laser (lambda = 473 nm), the
      combination of GFP and photosensitizers induces a selective elimination of GFP
      expressing CTCs, with limited effect on normal cells. In GFP-expressing cancer
      cell-infused or transplanted mice models, the treatment suppressed distant
      metastasis and extended the survival of the tumor-bearing mice. Taken together,
      CTCs are a core seed to be metastasized into secondary organs and elimination of
      CTCs may improve the survival of cancer patients.

PMID- 30201020
TI  - Mutational signature distribution varies with DNA replication timing and strand
      asymmetry.
AB  - BACKGROUND: DNA replication plays an important role in mutagenesis, yet little is
      known about how it interacts with other mutagenic processes. Here, we use somatic
      mutation signatures-each representing a mutagenic process-derived from 3056
      patients spanning 19 cancer types to quantify the strand asymmetry of mutational
      signatures around replication origins and between early and late replicating
      regions. RESULTS: We observe that most of the detected mutational signatures are
      significantly correlated with the timing or direction of DNA replication. The
      properties of these associations are distinct for different signatures and shed
      new light on several mutagenic processes. For example, our results suggest that
      oxidative damage to the nucleotide pool substantially contributes to the
      mutational landscape of esophageal adenocarcinoma. CONCLUSIONS: Together, our
      results indicate an interaction between DNA replication, the associated damage
      repair, and most mutagenic processes.

PMID- 30201022
TI  - Doing trials within trials: a qualitative study of stakeholder views on barriers
      and facilitators to the routine adoption of methodology research in clinical
      trials.
AB  - BACKGROUND: Randomised controlled trials are the cornerstone of evidence-based
      health care, yet many trials struggle with recruitment and retention. All too
      often the methodologies employed to address these problems are not evidence
      based, as rigorous methodological research on these issues is rare. The current
      research sought to identify barriers to the routine implementation of methodology
      research around recruitment and retention. METHODS: All registered UK clinical
      trials unit directors were sent a short questionnaire and invited to interview.
      Representatives of funding bodies and other stakeholders were also approached.
      Interviews were recorded and the content analysed. RESULTS: Data were grouped
      into four themes: acceptance of the need for methodological research; trial
      funding and development; trial processes; and organisational factors. The need to
      improve the evidence base for trials methodology is well established, but
      numerous barriers to implementation were perceived. CONCLUSIONS: The knowledge
      and expertise required to routinely implement methodology research exists within
      the current research structures, and there are clear opportunities to develop the
      evidence base. However, for this to be achieved there is also a need for clear
      strategic coordination within the sector and promotion of the necessary
      resources.

PMID- 30201023
TI  - Vertical stratification of Culicoides biting midges at a Florida big game
      preserve.
AB  - BACKGROUND: Many important vector arthropods are known to stratify vertically in
      forest environments, a phenomenon which has important implications for vector
      borne disease transmission and vector control. Culicoides Latreille biting midges
      (Diptera: Ceratopogonidae) have been documented using the forest canopy; however,
      studies of this phenomenon are lacking for many Culicoides species found in great
      abundance in the state of Florida, USA, some of which have been implicated as
      suspected vectors of hemorrhagic diseases of white-tailed deer. The present study
      aimed to determine whether common Culicoides species in Florida stratify
      vertically and to determine whether strata used by midges corresponded to host
      use. METHODS: Trapping was conducted at a big game preserve in Gadsden County,
      FL, USA. Over two summer field seasons in 2016 and 2017, CDC miniature light
      traps were set at two levels, one set at 1.37 m, designated as the ground trap,
      and a nearby trap in the forest canopy set at 6 m during 2016 and 9 m during
      2017. Species abundance, physiological status, and blood-meal sources were
      analyzed and compared between trap heights. RESULTS: Species abundances for C.
      haematopotus, C. stellifer and C. venustus were not significantly different
      between trap heights during the 2016 season; however, canopy traps were found to
      have significantly higher abundance of C. arboricola, C. biguttatus, C.
      debilipalpis, C. haematopotus, C. insignis and C. stellifer than ground traps in
      2017. Greater numbers of blood-engorged midges were collected in the canopy
      compared with ground traps during both study years, and 98.6% and 98.7% of blood
      meals from canopy collected midges were taken from ground-dwelling mammals in
      2016 and 2017, respectively. CONCLUSIONS: Culicoides species in Florida,
      including species implicated as vectors of hemorrhagic disease viruses, are found
      in great abundance in the forest canopy. Many midges are feeding on host species
      that are known reservoirs of hemorrhagic disease and then moving into the forest
      canopy, which has implications for the calculation of vectorial capacity. These
      data contribute valuable ecological information on Culicoides species found in
      Florida and provide a framework for developing effective vector control
      strategies to target these species.

PMID- 30201024
TI  - The efficacy and safety of herbal medicine BHH10 in postmenopausal women with
      osteoporosis: study protocol for a phase II, multicenter, randomized, double
      blinded, placebo-controlled clinical trial.
AB  - BACKGROUND: Osteoporosis is becoming more prevalent in aging societies worldwide,
      and the economic burden attributable to osteoporotic fractures is substantial.
      The medications presently available to treat osteoporosis have side effects, and
      the development of safer and more effective treatments is urgently needed. The
      aim of this study is to evaluate the efficacy and safety of BHH10, a traditional
      Korean herbal medicine, in the treatment of postmenopausal osteoporosis.
      METHODS/DESIGN: This is a phase II, multicenter, randomized, double-blinded,
      placebo-controlled clinical trial and will include 168 postmenopausal women aged
      55 years and older with osteoporosis. The participants will be recruited
      competitively from two sites of the Acupuncture and Moxibustion Department of
      Kyung Hee University Hospital of Korean Medicine, either Hoegidong or Gangdong in
      Seoul, Korea. Participants will be assigned randomly to one of two groups, the
      BHH10 group or the placebo group, in a 1:1 ratio, and will have five scheduled
      visits. Participants will take two tablets of BHH10 or placebo three times daily
      for 12 weeks. The primary efficacy outcome is the change in bone mineral density
      at the lumbar spine (L1-4) between baseline (visit 1) and 12 weeks after
      randomization (visit 5). Other outcome variables include changes in bone turnover
      markers, the Deficiency Syndrome of the Kidney Index, EuroQol five-dimension
      questionnaire score, and laboratory parameters, as well as adverse events.
      DISCUSSION: To our knowledge, this will be the first clinical trial to assess the
      efficacy and safety of BHH10 in postmenopausal women with osteoporosis. It is
      anticipated that the results will contribute to the development of traditional
      herbal medicines that can be used to treat osteoporosis in postmenopausal women
      in Korea. If the superiority of BHH10 over placebo is demonstrated, this study
      could provide the foundation for a phase III clinical trial. The results of the
      study will be published in a peer-reviewed journal. TRIAL REGISTRATION: Clinical
      Research Information Service, KCT0001842 . Registered on 14 March 2016.

PMID- 30201025
TI  - Nerve injury in severe trauma with upper extremity involvement: evaluation of
      49,382 patients from the TraumaRegister DGU(r) between 2002 and 2015.
AB  - BACKGROUND: Peripheral nerve injury (PNI) as an adjunct lesion in patients with
      upper extremity trauma has not been investigated in a Central European setting so
      far, despite of its devastating long-term consequences. This study evaluates a
      large multinational trauma registry for prevalence, mechanisms, injury severity
      and outcome characteristics of upper limb nerve lesions. METHODS: After formal
      approval the TraumaRegister DGU(r) (TR-DGU) was searched for severely injured
      cases with upper extremity involvement between 2002 and 2015. Patients were
      separated into two cohorts with regard to presence of an accompanying nerve
      injury. For all cases demographic data, trauma mechanism, concomitant lesions,
      severity of injury and outcome characteristics were obtained and group
      comparisons performed. RESULTS: About 3,3% of all trauma patients with upper limb
      affection (n = 49,382) revealed additional nerve injuries. PNI cases were more
      likely of male gender (78,6% vs.73,2%) and tended to be significantly younger
      than their counterparts without nerve lesions (mean age 40,6 y vs. 47,2 y).
      Motorcycle accidents were the most frequently encountered single cause of injury
      in PNI patients (32,5%), whereas control cases primarily sustained their trauma
      from high or low falls (32,2%). Typical lesions recognized in PNI patients were
      fractures of the humerus (37,2%) or ulna (20,3%), vascular lacerations (arterial
      10,9%; venous 2,4%) and extensive soft tissue damage (21,3%). Despite of similar
      average trauma severity in both groups patients with nerve affection had a longer
      primary hospital stay (30,6 d vs. 24,2 d) and required more subsequent inpatient
      rehabilitation (36,0% vs. 29,2%). CONCLUSION: PNI complicating upper extremity
      trauma might be more commonly encountered in Central Europe than suggested by
      previous foreign studies. PNI typically affect males of young age who show
      significantly increased length of hospitalization and subsequent need for
      inpatient rehabilitation. Hence these lesions induce extraordinary high financial
      expenses besides their impact on health related quality of life for the
      individual patient. Further research is necessary to develop specific prevention
      strategies for this kind of trauma.

PMID- 30201027
TI  - Associations of children's Big Five personality with eating behaviors.
AB  - OBJECTIVE: Our aim is to examine the associations of the Big Five personality
      factors with eating behaviors in children using a cross-sectional study in 1543
      randomly Norwegian 7-12 year olds. RESULTS: Mothers rated the hierarchical
      personality inventory for children, and the child eating behaviour questionnaire
      to describe her child. Personality and eating behaviors were substantially
      associated in bivariate correlations and multivariate analyses of variance. The
      strongest predictors of eating behaviors were neuroticism, followed by
      agreeableness and conscientiousness. Neuroticism correlated the highest with slow
      eating, emotional undereating, food responsiveness, and emotional overeating, and
      showed minor associations with satiety responsiveness, and fussiness. Neuroticism
      was not associated with enjoyment of food. Agreeableness was associated with low
      fussiness, low emotional undereating, low food responsiveness and low emotional
      overeating, conscientiousness was associated with low satiety responsiveness, and
      food responsiveness, and extraversion and imagination were associated with high
      enjoyment of food.

PMID- 30201028
TI  - Genetic diversity of Escherichia coli isolated from ice cube production sites.
AB  - OBJECTIVE: The prevalence of Escherichia coli including from ice cubes in
      Indonesia is quite high. Unfortunately, little is known about the genetic
      diversity of E. coli from ice cube production site. Genotypic variation in E.
      coli populations is a major barrier to control public health risk associated with
      foodborne pathogen. The aims of this study were to analyze the genotypic
      diversity of E. coli strains isolated from various samples in order to determine
      the genetic relationship between those strains. This study is also important to
      understand the occurrence, prevalence and profile picture of different pathogenic
      E. coli in various sources which potentially cause disease. RESULTS:
      Enterobacterial repetitive intergenic consensus (ERIC) and repetitive extragenic
      palindromic polymerase chain reaction (REP-PCR) dendrogram showed high genetic
      diversity of 120 E. coli isolates in majority of sampling sites. DNA fingerprint
      patterns showed 26 and 21 clusters with 11 and 3 fingerprints individual lineages
      for ERIC and REP-PCR respectively. There was no correlation observed between
      phylogenetic relationship and virulence genes. The result indicated a variation
      of E. coli isolates in ice cube manufacturers. ERIC-PCR method is more
      discriminative compared with REP-PCR to analyze the genetic diversity of E. coli
      from ice cubes production sites.

PMID- 30201026
TI  - Risk factors for damage in childhood-onset systemic lupus erythematosus in
      Asians: a case control study.
AB  - BACKGROUND: Accumulated damage is an important prognostic factor in systemic
      lupus erythematous. However, the pattern of disease damage and its risk factors
      have not been well studied in childhood-onset systemic lupus erythematosus (cSLE)
      in Asia. The objectives are to evaluate the pattern of damage and to identify the
      risk factors for accumulated damage in an Asian group of cSLE. METHODS: A
      retrospective chart review was conducted on a group of 59 patients with cSLE.
      Patient demographics and clinical variables were first collected at diagnosis.
      Over the course of their disease, clinical variables considered as risk factors
      for damage were also collected. Damage was measured using the Systemic Lupus
      International Collaborating Clinics/ American College of Rheumatology Damage
      Index (SDI) for each patient at their last encounter. Based on their SDI scores,
      patients were then dichotomized to two groups: a group with presence of disease
      damage (SDI >=1) and a group with absence of disease damage (SDI score = 0).
      Clinical variables including age at diagnosis, gender, ethnicity, disease
      duration, disease manifestations, laboratory values at diagnosis, disease
      activity at diagnosis and last encounter, major organ involvement, number of
      lupus flares, major infection, and intensity of immunosuppressive medications
      were compared between the two groups. Growth failure and estimated glomerular
      filtration rate (eGFR) were also analysed as secondary outcomes. RESULTS: After a
      median disease duration and follow up of 7.8 years, 39 patients (66.1%) had no
      disease damage while 20 patients (33.9%) had acquired disease damage. Disease
      damage most frequently occurred in the ocular (15.3%), neuropsychiatric (11.9%)
      and musculoskeletal (11.9%) domains. The most frequent forms of damage were
      cataracts (11.9%), and avascular necrosis (unilateral and bilateral combined
      10.2%). After controlling for other variables, presence of neuropsychiatric
      manifestations remained the only statistically significant risk factor for
      damage. The rate of growth failure in our group of patients was 16%. Patients who
      experienced growth failure were significantly younger at disease diagnosis. The
      median age of diagnosis was 10 for those who experienced growth failure, whereas
      the median age of diagnosis was 13 for those who did not experience growth
      failure. Despite a high rate of renal involvement in the group (79.7%), renal
      damage was only seen in 3.2% of the patients. 91.5% of the studied group had
      normal eGFR of >=90 ml/min/1.73m2 at their last follow up. CONCLUSION: This group
      of patients had a low rate of damage accrual, with one of the lowest rates in
      renal damage when compared to other cohorts reported. The presence of
      neuropsychiatric manifestations was identified as the most significant risk
      factor for disease damage, while the most frequent forms of damage were cataracts
      and avascular necrosis, which were both related to prolonged steroid use. Despite
      the limitations of this study, it highlights the need for larger prospective
      studies to understand the relationship between childhood-onset SLE and its
      resulting damage.

PMID- 30201030
TI  - Correction to: Comorbidity in gout at the time of first diagnosis: sex
      differences that may have implications for dosing of urate lowering therapy.
AB  - Unfortunately, after publication of this article [1], it was noticed that Fig. 2
      is incorrect.

PMID- 30201029
TI  - Clinical research on the efficacy and safety of thread-embedding acupuncture for
      treatment of herniated intervertebral disc of the lumbar spine: a protocol for a
      multicenter, randomized, patient-assessor blinded, controlled, parallel, clinical
      trial.
AB  - BACKGROUND: A lumbar herniated intervertebral disc (LHIVD) is a common problem
      that usually causes lower back pain and neurological symptoms that manifest as
      radiating pain. Several studies have reported that thread-embedding acupuncture
      (TEA) is effective in the treatment of LHIVD. However, these studies were of low
      quality and there is therefore little clinical evidence for the effectiveness of
      TEA in this regard. The aim of the present study is to establish the clinical
      evidence regarding the efficacy and safety of TEA in the treatment of pain,
      function, and quality of life in patients with LHIVD. The study uses a rigorously
      designed, full-scale, randomized clinical trial (RCT) protocol. METHOD/DESIGN:
      This is a multicenter, randomized, patient-assessor blinded, sham-controlled
      trial with two parallel arms. Seventy patients with LHIVD who have lower back
      pain more severe than 40 mm on the 100-mm visual analogue scale (VAS), and who
      are aged 19-70 years, will be recruited and randomly allocated to a TEA group and
      sham TEA (STEA) group. Both groups will receive treatment on 23 predefined
      acupoints once a week for eight weeks; needles with the thread removed will be
      used in the STEA group, while normal TEA will be employed in the TEA group.
      Changes in the 100-mm VAS for lower back pain after eight weeks will be assessed
      as the primary outcome. Furthermore, the 100-mm VAS for radiating pain, Oswestry
      Disability Index, Roland-Morris disability questionnaire, EuroQol 5 Dimensions 5
      Levels, and global perceived effect will be measured and analyzed as secondary
      outcomes. All outcomes will be assessed at baseline and at 4, 8, 12, and 16 weeks
      after screening. DISCUSSION: The results of this trial will help to establish the
      clinical evidence regarding TEA in the treatment of patients with LHIVD. TRIAL
      REGISTRATION: ClinicalTrials.gov, NCT03236753 . Registered on August 2, 2017.
      Clinical Research Information Service of the Republic of Korea, KCT0002439 .
      Registered on August 1, 2017.

PMID- 30201032
TI  - Ivermectin-induced fixed drug eruption in an elderly Cameroonian: a case report.
AB  - BACKGROUND: Cutaneous adverse reactions to medications are extremely common and
      display characteristic clinical morphology. A fixed drug eruption is a cutaneous
      adverse drug reaction due to type IV or delayed cell-mediated hypersensitivity.
      Ivermectin, a broad-spectrum anti-parasitic compound, has been an essential
      component of public health campaigns targeting the control of two devastating
      neglected tropical diseases: onchocerciasis (river blindness) and lymphatic
      filariasis. CASE PRESENTATION: We report the case of a 75-year-old Cameroonian
      man of the Bamileke ancestry who developed multiple fixed drug eruptions a few
      hours following ivermectin intake that worsened with repeated drug consumption.
      Discontinuation of the drug, counselling, systemic steroids, and orally
      administered antihistamines were the treatment modalities employed. Marked
      regression of the lesions ensued with residual hyperpigmentation and dyschromia.
      CONCLUSION: Keen observation on the part of physicians is mandatory during the
      administration of ivermectin for quick recognition and prevention of this adverse
      drug reaction.

PMID- 30201031
TI  - Efficacy of two formulations of afoxolaner (NexGard(r) and NexGard Spectra(r))
      for the treatment of generalised demodicosis in dogs, in veterinary dermatology
      referral centers in Europe.
AB  - BACKGROUND: A multi-centre field trial was conducted to evaluate the efficacy of
      afoxolaner based chewables (NexGard(r) or NexGard Spectra(r)) for the treatment
      of generalised demodicosis caused by Demodex canis in dogs under field conditions
      in France, Italy and Poland. METHODS: Client-owned dogs, diagnosed positive for
      Demodex mites by pre-treatment skin scrapings and presenting clinical signs of
      generalised demodicosis were included. Dogs were orally treated with afoxolaner
      three times at monthly intervals. Of the 50 dogs enrolled, 48 completed the whole
      study. Efficacy of the treatments was assessed monthly by Demodex mite counts and
      physical examination with special regard to the severity and extension of skin
      lesions. RESULTS: Treatments were well tolerated in all dogs and resulted in a
      rapid reduction of mites, with all post-treatment mite counts significantly lower
      than baseline. The number of mites was reduced by 87.6%, 96.5% and 98.1% on Days
      28, 56 and 84, respectively. In addition, the skin lesion severity and extent
      scores as well as the pruritus were all significantly lower at all post-treatment
      visits compared to the pre-treatment assessment. CONCLUSIONS: This clinical field
      study demonstrated that monthly administrations of afoxolaner in NexGard(r) or
      NexGard Spectra(r), offered a convenient and reliable solution for the treatment
      of canine generalised demodicosis.

PMID- 30201033
TI  - Socio-demographic determinants of childhood immunization incompletion in
      Koforidua, Ghana.
AB  - OBJECTIVE: Immunization saves more than 3 million lives worldwide each year, and
      it saves millions from suffering illness and lifelong disability. The study
      sought to assess the socio-demographic factors that influence childhood
      immunization incompletion. A cross-sectional descriptive design was employed for
      the study conducted at the Child Welfare Clinic in the Regional Hospital,
      Koforidua. A total of 280 caregivers/mothers who have children aged between 0 and
      59 months were included in this study. Data were entered and analyzed using SPSS.
      RESULTS: The study found that being divorced (p = 0.048) and working part-time (p
      = 0.049) has a significant and positive association with immunization
      incompletion. Women who were divorced [AOR (95% CI) 3.01 (1.59-58.2)] were 3
      times less likely to complete immunization than those who were cohabiting,
      married and widowed taken into account the effect due to all the additional
      confounder variables included in the analysis. Women who were working part-time
      were 2.28 times less likely to complete immunization schedule than those working
      full-time; [AOR (95% CI) 2.28 (1.031-9.11)]. This study has documented socio
      demographic factors influencing childhood immunization incompletion in the
      Regional Hospital, Koforidua. The Ministry of Health should, therefore, put in
      measures like public education to encourage mothers to complete each immunization
      schedule.

PMID- 30201034
TI  - Acceptability of the dengue vaccination among parents in urban poor communities
      of Quezon City, Philippines before and after vaccine suspension.
AB  - OBJECTIVE: The study aims to illustrate the acceptability of the dengue vaccine
      before and after the dengue vaccination suspension in urban poor communities in
      Quezon City, Philippines. RESULTS: There were 12 interviews conducted in November
      2017 and 5 focus group discussions in January 2018, a month after vaccine program
      suspension with 41 participants. All participants were selected through purposive
      criterion sampling. Thematic analysis showed acceptability of the dengue vaccine
      was associated with parental experience with vaccination and dengue, trust in
      public health institutions and communication received by parents. Post-dengue
      vaccination suspension triangulation indicated that the parents regretted the
      experience, trust to public institutions was eroded and the communication
      strategy was deemed inadequate. This led to low vaccine acceptability post
      vaccine suspension.

PMID- 30201035
TI  - Lamivudine plus tenofovir combination therapy versus lamivudine monotherapy for
      HBV/HIV coinfection: a meta-analysis.
AB  - BACKGROUND: Currently, there is no consensus on the efficacy and safety of
      lamivudine (LAM) plus tenofovir disoproxil fumarate (TDF) combination therapy
      versus lamivudine monotherapy in HBV/HIV coinfected patients. METHODS: A
      comprehensive literature search was performed in English and Chinese databases.
      Both relevant dichotomous and continuous variables were extracted, and the
      combined outcomes were expressed as a risk ratio (RR) or a standard mean
      difference (SMD). RESULTS: Eleven eligible studies were included in our analysis.
      For HBV-relevant outcomes, the proportion of patients with undetectable HBV, the
      rates of serum alanine aminotransferase (ALT) normalization and hepatitis B e
      antigen (HBeAg) loss were higher in the combination therapy group than the
      monotherapy group (RR = 1.42, 95% CI: 1.14-1.76, P = 0.002; RR = 1.36, 95% CI:
      1.17-1.58, P < 0.0001; RR = 2.74, 95% CI: 1.20-6.22, P = 0.02). In addition, the
      rate of HIV RNA-negative conversion was higher in the combination therapy group
      than the monotherapy group (RR = 1.26, 95% CI: 1.11-1.42, P = 0.0003).
      CONCLUSION: LAM plus TDF combination therapy was more efficacious than LAM
      monotherapy in HBV/HIV coinfected patients. As time passes, this difference
      becomes more pronounced.

PMID- 30201036
TI  - The effects of zinc amino acid complex supplementation on the porcine host
      response to Lawsonia intracellularis infection.
AB  - Lawsonia intracellularis is among the most important enteric pathogens of swine
      and antibiotic alternatives are needed to help mitigate the negative effects of
      infection. Zinc is an essential trace mineral known to be crucial for maintaining
      intestinal barrier function and proper immune response. In this study, we
      investigated the porcine host response to L. intracellularis infection when
      supplemented with a zinc-amino acid complex, a form of zinc that can lead to
      greater bioavailability when compared to traditional inorganic forms of zinc. Our
      results show that a zinc-amino acid complex supplementation with a final
      concentration of 125 ppm of zinc in feed significantly (p < 0.05) decreased the
      number of animals with lesions and severity of lesions caused by L.
      intracellularis. Animals supplemented with the zinc-amino acid complex also
      exhibited a significantly (p < 0.05) earlier onset of seroconversion as well as
      an increased number of T cells in infected and non-infected intestinal tissue.
      This study demonstrated that this zinc-amino acid complex aids the host in
      responding to L. intracellularis infection and may be a new approach to help
      minimize negative effects of disease.

PMID- 30201037
TI  - Dispersion of Lutzomyia longipalpis and expansion of visceral leishmaniasis in
      Sao Paulo State, Brazil: identification of associated factors through survival
      analysis.
AB  - BACKGROUND: In Brazil, visceral leishmaniasis (VL) is a serious public health
      problem because of its magnitude, geographical expansion and potential harms
      caused by illnesses, including death. However, VL is largely ignored in
      discussions of tropical disease priorities. Thus, this study aimed to identify
      factors associated with the expansion of VL and the dispersion of its vector,
      Lutzomyia longipalpis, in the municipalities of the State of Sao Paulo, Brazil.
      METHODS: Information about the date of vector detection and the confirmation of
      autochthonous VL occurrence in humans and canines in Sao Paulo were obtained
      between 1997 and 2014. Survival curves were calculated by the Kaplan-Meier and
      the Cox multiple regression models was used. RESULTS: The presence of the
      Marechal Rondon highway showed the highest positive association with vector
      dispersion and canine and human VL expansion. The monthly maximum and minimum
      temperature averages recorded in the municipalities during the study period were
      also positively associated with these events. The presence of transverse highways
      was positively associated with the presence of the vector; the border with the
      State of Mato Grosso do Sul, the presence of a prison, microregion headquarters,
      and the presence of the Tiete River were positively associated with the
      occurrence of canine cases, while only the presence of prison was positively
      associated with the occurrence of human cases. The construction of the Bolivia
      Brazil gas pipeline was not associated with any events. CONCLUSIONS: Survival
      analysis enabled the identification of factors associated with vector dispersion
      and VL expansion, thus the results of this study may be useful to the improvement
      of VL surveillance and control activities in the State of Sao Paulo and
      throughout Brazil.

PMID- 30201038
TI  - Monosodium urate crystals reduce osteocyte viability and indirectly promote a
      shift in osteocyte function towards a proinflammatory and proresorptive state.
AB  - BACKGROUND: Bone erosion is a frequent complication of gout and is strongly
      associated with tophi, which are lesions comprising inflammatory cells
      surrounding collections of monosodium urate (MSU) crystals. Osteocytes are
      important cellular mediators of bone remodeling. The aim of this study was to
      investigate the direct effects of MSU crystals and indirect effects of MSU
      crystal-induced inflammation on osteocytes. METHODS: For direct assays, MSU
      crystals were added to MLO-Y4 osteocyte cell line cultures or primary mouse
      osteocyte cultures. For indirect assays, the RAW264.7 macrophage cell line was
      cultured with or without MSU crystals, and conditioned medium from these cultures
      was added to MLO-Y4 cells. MLO-Y4 cell viability was assessed using alamarBlue(r)
      and LIVE/DEAD(r) assays, and MLO-Y4 cell gene expression and protein expression
      were assessed by real-time polymerase chain reaction (PCR) and enzyme-linked
      immunosorbent assay (ELISA), respectively. Histological analysis was used to
      examine the relationship between MSU crystals, inflammatory cells, and osteocytes
      in human joints affected by tophaceous gout. RESULTS: In direct assays, MSU
      crystals reduced MLO-Y4 cell and primary mouse osteocyte viability but did not
      alter MLO-Y4 cell gene expression. In contrast, conditioned medium from MSU
      crystal-stimulated RAW264.7 macrophages did not affect MLO-Y4 cell viability but
      significantly increased MLO-Y4 cell expression of osteocyte-related factors
      including E11, connexin 43, and RANKL, and inflammatory mediators such as
      interleukin (IL)-6, IL-11, tumor necrosis factor (TNF)-alpha and cyclooxygenase-2
      (COX-2). Inhibition of COX-2 in MLO-Y4 cells significantly reduced the indirect
      effects of MSU crystals. In histological analysis, CD68+ macrophages and MSU
      crystals were identified in close proximity to osteocytes within bone. COX-2
      expression was also observed in tophaceous joint samples. CONCLUSIONS: MSU
      crystals directly inhibit osteocyte viability and, through interactions with
      macrophages, indirectly promote a shift in osteocyte function that favors bone
      resorption and inflammation. These interactions may contribute to disordered bone
      remodeling in gout.

PMID- 30201039
TI  - The effectiveness of a group-based computerized HIV/STI prevention intervention
      for black women who use drugs in the criminal justice system: study protocol for
      E-WORTH (Empowering African-American Women on the Road to Health), a Hybrid Type
      1 randomized controlled trial.
AB  - BACKGROUND: This paper describes the study protocol of a hybrid type I randomized
      controlled trial that evaluates the effectiveness and cost-effectiveness of
      implementing Empowering African-American Women on the Road to Health (E-WORTH),
      an Afrocentric, group-based, computerized human immunodeficiency virus
      (HIV)/sexually transmitted infection (STI) prevention intervention for controlled
      substance-using black women in community corrections settings in New York City.
      METHODS/DESIGN: We provide an overview of E-WORTH's hybrid type I design, which
      is guided by the Consolidated Framework for Implementation Research (CFIR). E
      WORTH combines HIV/STI and intimate partner violence (IPV) prevention components
      and tests the comparative effectiveness of E-WORTH and streamlined HIV testing
      versus streamlined HIV testing alone in decreasing biologically confirmed HIV and
      STI incidence, sexual risk, and IPV, as well as in improving access to HIV and
      STI prevention services and care. DISCUSSION: This paper provides an overview of
      E-WORTH's intervention protocol and serves as a framework for using hybrid type I
      designs, guided by the CFIR conceptual framework, to evaluate HIV/STI and IPV
      prevention interventions in community corrections settings. We discuss how E
      WORTH's hybrid type I design advances implementation science through its
      effectiveness and cost-effectiveness aims as well as through a mixed-methods
      study that evaluates multilevel theory-driven factors (structural,
      organizational, staffing, and client) guided by the CFIR that influences the
      implementation of E-WORTH in a criminal justice setting. This study also
      addresses the novel challenges and opportunities of implementing an intervention
      that targets specific racial subgroup(s) in a community corrections setting that
      services all populations, implementing a group-based intervention with
      technological components in such settings, and employing community-based
      participatory research strategies to guide recruitment and retention efforts.
      TRIAL REGISTRATION: ClinicalTrials.gov, NCT02391233 . Registered on 17 March
      2015.

PMID- 30201041
TI  - Detection of Streptococcus pneumoniae from culture-negative dried blood spots by
      real-time PCR in Nigerian children with acute febrile illness.
AB  - OBJECTIVES: Acute febrile illness is a common cause of hospital admission, and
      its associated infectious causes, of which a key bacterial causative agent is
      Streptococcus pneumoniae, contribute to substantial morbidity and mortality. We
      sought to evaluate the utility of real-time (rt)-PCR on dried blood spots (DBS)
      for diagnosis of S. pneumoniae in acute febrile illness among children presenting
      to hospitals in Nigeria. We previously described preliminary results in a sample
      of 537 patients. Here we present data from a larger collection of 1038 patients.
      RESULTS: Using rt-PCR for Streptococcus pneumoniae on 1038 dried blood spots from
      children prospectively enrolled with acute febrile illness, including 79 healthy
      controls, we detected pneumococcal DNA in nine of 15 blood culture-positive
      specimens, one culture-negative specimen from a high-risk group, a culture
      confirmed non-pneumococcal specimen and a healthy control. Six culture-positive
      isolates (40%) were negative. Sensitivity was 60%, specificity 99.7%, positive
      predictive value 75% and negative predictive value 99.4%. Rt-PCR of DBS has
      limited sensitivity in blood specimens from acute febrile illness in children.

PMID- 30201042
TI  - Triage skill and associated factors among emergency nurses in Addis Ababa,
      Ethiopia 2017: a cross-sectional study.
AB  - OBJECTIVE: The aim of this study was to assess levels of triage skill and
      associated factors among emergency nurses in Addis Ababa, Ethiopia, 2017.
      RESULTS: Above half of the participants (52.9%) had a moderate level of triage
      skill. A strong positive relationship was found between nurses' level of triage
      knowledge and skill (r = .68, p .01). Knowledge about triage, educational level
      and training experience had a significant relationship with triage skill with (B
      = 1.09, CI (1.41, 1.77), p = .002), (B = - 19.96, CI (- 30.208, - 9.715), p =
      .001), (B = .55, CI .16, .94), p = .006) respectively. This study revealed that
      most triage nurses had a moderate level of skills. Therefore, the ministry of
      health and hospitals should provide training and education to improve triage
      skill.

PMID- 30201040
TI  - Enhancing maternal and infant wellbeing: study protocol for a feasibility trial
      of the Baby Triple P Positive Parenting programme for mothers with severe mental
      health difficulties (the IMAGINE study).
AB  - BACKGROUND: There is a strong evidence base for the benefits of parenting
      interventions for parents without severe mental illness (SMI). As the impact of
      maternal SMI can be significant on child development, mothers need support to
      maximise outcomes for themselves and their children. Some mothers with SMI
      require admission jointly with their baby to a Mother and Baby Unit (MBU), a
      psychiatric inpatient ward, for assessment and treatment. However, MBUs do not
      yet offer formally evaluated, evidence-based parenting interventions as a matter
      of routine. This paper describes a study to investigate the feasibility and
      acceptability of conducting a randomised controlled trial (RCT) to evaluate a
      parenting and psychological intervention targeting the mother's and infant's
      wellbeing for mothers admitted to a MBU. METHODS/DESIGN: This study is a
      multisite, single-blind feasibility trial with half the participants randomised
      to the Baby Triple P Positive Parenting Programme plus treatment as usual (TAU)
      and the other half randomised to TAU alone. Self-report and observer-rated
      assessments are collected at baseline, 10 weeks post-baseline and 6 months post
      baseline. Participants are mothers admitted to a MBU in the Northwest of England
      or the Midlands. Participants are included if they are fluent in English to
      provide informed, written consent. Our objective is to determine whether we can
      recruit 66 women, randomise 60, and retain them in the intervention and study,
      and whether the intervention and study procedures are acceptable. As part of a
      nested process evaluation, qualitative interview data from trial participants and
      MBU staff will inform feasibility and acceptability. The feasibility of
      collecting data required to conduct an economic evaluation of the intervention
      will also be explored. DISCUSSION: Although research has been conducted in
      relation to mothers with severe mental illness and MBUs, to our knowledge, this
      is the first controlled trial to test the feasibility, acceptability, uptake and
      retention alongside the potential efficacy of a parenting intervention for this
      population. This study is essential to examine the contextual challenges involved
      in this setting with this population and to identify any refinements required.
      TRIAL REGISTRATION: ISRCTN12765736 . Date of first registration: 2 February 2017.

PMID- 30201043
TI  - Herbal medicine foot bath for the treatment of diabetic peripheral neuropathy:
      protocol for a randomized, double-blind and controlled trial.
AB  - BACKGROUND: As a common complication of diabetes, the incidence of diabetic
      peripheral neuropathy (DPN) is 60-70% worldwide. DPN is a major risk factor for
      diabetic foot, which may lead to foot ulceration and even amputation. The
      treatment of DPN remains challenging. Our preliminary study demonstrated that the
      external application of Tangbi Waixi (TW) decoction to the lower extremities
      relieved clinical symptoms and improved nerve conduction velocity in DPN
      patients. The aim of this study was to verify the efficacy of TW among DPN
      patients and evaluate the herb mixture's safety using rigorous methodological
      designs. METHODS/DESIGN: This study is a multicenter, double-blind, randomized
      controlled trial. A total of 640 DPN patients will be recruited and randomized to
      receive a foot bath with either the TW decoction or control drug. Participants
      will be assessed at baseline and 12 and 24 weeks after treatment. The primary
      outcome was the change of the Toronto Clinical Scoring System (TCSS). Secondary
      outcomes were nerve conduction velocity, blood glucose, blood lipids, serum
      inflammatory cytokines, and the European Quality of Life Five-Dimension Scale (EQ
      5D) and TCM symptom scores. DISCUSSION: This multicenter, prospective, randomized
      clinical trial will provide valuable data regarding the efficacy and safety of
      foot bath treatment with TW decoction. Positive results would provide a novel
      treatment regimen for DPN patients. TRIAL REGISTRATION: Chinese Clinical Trial
      Registry, ChiCTR-IOR-16009331 . Registered on 8 October 2016.

PMID- 30201045
TI  - Epidemiology of self-medication in Ethiopia: a systematic review and meta
      analysis of observational studies.
AB  - BACKGROUND: Self-medication is the use of drugs to treat self-diagnosed disorders
      and/or symptoms, or the intermittent or continued use of a prescribed drug for
      recurrent disease or symptoms. This phenomenon is alarmingly increasing over time
      despite the occurrence of health-related hazards. This study is, therefore, aimed
      to quantitatively estimate self-medication practice and possible reasons for it
      in Ethiopia. METHODS: Data were identified from major databases and indexing
      services including EMBASE (Ovid), PubMed, MEDLINE (Ovid), and Google Scholar.
      Both published and unpublished records addressing self medication practice in
      Ethiopia without time limit were included for the study. Data were extracted with
      structured format prepared in Microsoft Excel and exported to OpenMeta[analyst]
      version 3.3 software for analyses. Pooled estimation of outcomes was performed
      with DerSimonian-Laird random-effects model at 95% confidence level. Sensitivity
      and subgroup analyses were also considered. Degree of heterogeneity of studies
      was presented with I2 statistics. Publication bias was also performed with the
      help of Comprehensive Meta-Analysis version-3 software and presented with funnel
      plots of standard error supplemented by Begg's and Egger's tests. The study
      protocol is registered on PROSPERO with reference number ID: CRD42018093790.
      RESULTS: A total of 27 studies with 9586 participants were included for the
      study. The pooled prevalence of self-medication in Ethiopia was found to be 44.0%
      (95% confidence interval [CI]: 35.1, 52.8). Geographical-based subgroup analysis
      revealed that the highest prevalence was observed at the capital of Ethiopia,
      Addis Ababa, 62.8% (95% CI: 42.3, 83.2). Population based analysis indicated that
      healthcare professionals and students were the main practitioners of self
      medication. Besides, the prevalence of self-medication practice in pregnant women
      is approximately 22.9% (95% CI: 9.8, 36). The most common reasons to practice
      self-medication were previous experience of clients and/or familiarity of
      treatments, 31.3% (95% CI: 21.5, 41.1) and perceived mildness of the illness,
      31.1% (95% CI: 26.0, 36.2). The pooled prevalence of analgesics, antimicrobial
      agents and gastrointestinal drugs were 46.1% (95% CI: 36.2, 56.1), 28.2% (95% CI:
      19.6, 36.8), and 14.9% (95% CI: 7.8, 21.9), respectively. CONCLUSION: Self
      medication practice becomes a common phenomenon in Ethiopia. The use of
      prescription-only medications including antimicrobial agents without medical
      consult has become alarmingly high. This practice will come with potential health
      related hazards including emergence of antimicrobial resistance. Therefore, there
      must be a multitude of strategies for reversing the current worrying trends of
      self-medication.

PMID- 30201046
TI  - Emergence of the arterial worm Elaeophora schneideri in moose (Alces alces) and
      tabanid fly vectors in northeastern Minnesota, USA.
AB  - BACKGROUND: Moose (Alces alces) are a culturally and economically valued species
      in Minnesota. However, the moose population has experienced a sudden, marked
      decline in their range, including extirpation in the northwest and a 66% decline
      in the last decade in the northeast portions of the state. Although the exact
      cause of this decline is unclear, parasitic metastrongylid and filarioid nematode
      infections are known causes of morbidity and mortality in moose across North
      America. METHODS: To determine if these parasitic nematodes could be contributing
      to the Minnesota moose population decline, we molecularly examined banked tissues
      obtained from moose that died of known and unknown causes for the presence of
      nematode DNA. Extracted brain DNA of 34 individual moose was amplified utilizing
      primers targeting the 18S rRNA gene and internal transcribed spacer regions of
      nematodes. RESULTS: DNA sequencing revealed that PCR products obtained from 15
      (44.1%) of the moose were 99% identical to Parelaphostrongylus tenuis, a
      metastrongylid known to cause neurological disease and death. Additionally, brain
      tissue from 20 (58.8%) individuals yielded sequences that most closely aligned
      with Elaeophora schneideri, a parasite associated with neurological impairment
      but previously unreported in Minnesota. Setaria yehi, a common filarioid parasite
      of deer, was also detected in the brain tissue of 5 (14.7%) moose. Molecular
      screening of 618 captured tabanid flies from four trapping sites revealed E.
      schneideri was present (6%) in the Minnesota environment and transmission could
      occur locally. Prevalence rates among the flies ranged between 0-100% per
      trapping site, with Chrysops spp. and Hybomitra spp. implicated as the vectors.
      CONCLUSIONS: Ultimately, these data confirm that P. tenuis is widespread in the
      Minnesota moose population and raises the question of the significance of E.
      schneideri as a contributing factor to morbidity and mortality in moose.

PMID- 30201047
TI  - Rational use of paracetamol among out-patients in a Bhutanese district hospital
      bordering India: a cross-sectional study.
AB  - OBJECTIVE: Paracetamol or acetaminophen is a weak analgesic commonly used
      worldwide and in Bhutan. It is available across all levels of Bhutan's health
      care system and for purchase without prescription. Little is known, however,
      about patterns of paracetamol use in Bhutan. This study aimed to assess what the
      Bhutanese population knows about the indications for use of paracetamol, safe
      use, and common patterns of usage (frequency, dosage). These questions were
      studied among Bhutanese living in Phuentsholing, a large commercial town at
      Bhutan-India border. RESULTS: Among 441 participants, most (72.1%) reported
      having used paracetamol in the past 1 year. The mean knowledge score was 57.6%;
      only 30 participants (6.8%) had what was characterized as "good knowledge." Level
      of knowledge was positively associated with level of education (p = 0.031). Less
      than half (41.3%) had a "good attitude" towards use of paracetamol. In practice,
      few (4.8%) knew the correct dose, including about one in ten who reported
      exceeding the recommended therapeutic dose. Most knew about side effects (61.2%)
      and possible allergic reactions (77.3%). Many participants (47.9%) acknowledged
      that the self-use of paracetamol may not reduce the number of hospital visits.

PMID- 30201044
TI  - Sex-specific differences in hepatic steatosis in obese spontaneously hypertensive
      (SHROB) rats.
AB  - BACKGROUND: Patients with metabolic syndrome, who are characterized by co
      existence of insulin resistance, hypertension, hyperlipidemia, and obesity, are
      also prone to develop non-alcoholic fatty liver disease (NAFLD). Although the
      prevalence and severity of NAFLD is significantly greater in men than women, the
      mechanisms by which gender modulates the pathogenesis of hepatic steatosis are
      poorly defined. The obese spontaneously hypertensive (SHROB) rats represent an
      attractive model of metabolic syndrome without overt type 2 diabetes. Although
      pathological manifestation caused by the absence of a functional leptin receptor
      has been extensively studied in SHROB rats, it is unknown whether these animals
      elicited sex-specific differences in the development of hepatic steatosis.
      METHODS: We compared hepatic pathology in male and female SHROB rats.
      Additionally, we examined key biochemical and molecular parameters of signaling
      pathways linked with hyperinsulinemia and hyperlipidemia. Finally, using methods
      of quantitative polymerase chain reaction (qPCR) and western blot analysis, we
      quantified expression of 45 genes related to lipid biosynthesis and metabolism in
      the livers of male and female SHROB rats. RESULTS: We show that all SHROB rats
      developed hepatic steatosis that was accompanied by enhanced expression of
      SREBP1, SREBP2, ACC1, and FASN proteins. The livers of male rats also elicited
      higher induction of Pparg, Ppara, Slc2a4, Atox1, Skp1, Angptl3, and Pnpla3 mRNAs.
      In contrast, the livers of female SHROB rats elicited constitutively higher
      levels of phosphorylated JNK and AMPK and enhanced expression of Cd36.
      CONCLUSION: Based on these data, we conclude that the severity of hepatic
      steatosis in male and female SHROB rats was mainly driven by increased de novo
      lipogenesis. Moreover, male and female SHROB rats also elicited differential
      severity of hepatic steatosis that was coupled with sex-specific differences in
      fatty acid transport and esterification.

PMID- 30201048
TI  - Quantification of variation and the impact of biomass in targeted 16S rRNA gene
      sequencing studies.
AB  - BACKGROUND: Recent advances in sequencing technologies and bioinformatics tools
      have allowed for large-scale microbiome studies that are rapidly advancing
      medical research. However, small changes in technique or analysis can
      significantly alter the results and lead to conflicting findings. Quantifying the
      technical versus biological variation expected in targeted 16S rRNA gene
      sequencing studies and how this variation changes with input biomass is critical
      to guide meaningful interpretation of the current literature and plan future
      research. RESULTS: Data were compiled from 469 sequencing libraries across 19
      separate targeted 16S rRNA gene sequencing runs over a 2.5-year time period.
      Following removal of contaminant sequences identified from negative controls, 244
      samples retained sufficient reads for further analysis. Coefficients of variation
      for intra- and inter-assay variation from repeated measurements of a bacterial
      mock community ranged from 8.7 to 37.6% (intra) and 15.6 to 80.5% (inter) for all
      but one genus of bacteria whose relative abundance was greater than 1%. Intra-
      versus inter-assay Bray-Curtis pairwise distances for a single stool sample were
      0.11 versus 0.31, whereas intra-assay variation from repeat stool samples from
      the same donor was greater at 0.38 (Wilcoxon p = 0.001). A dilution series of the
      bacterial mock community was used to assess the effect of input biomass on
      variability. Pairwise distances increased with more dilute samples, and estimates
      of relative abundance became unreliable below approximately 100 copies of the 16S
      rRNA gene per microliter. Using this data, we created a prediction model to
      estimate the expected variation in microbiome measurements for given input
      biomass and relative abundance values. CONCLUSIONS: Well-controlled microbiome
      studies are sufficiently robust to capture small biological effects and can
      achieve levels of variability consistent with clinical assays. Relative abundance
      is negatively associated with measures of variability and has a stronger effect
      on variability than does absolute biomass, suggesting that it is feasible to
      detect differences in bacterial populations in very low-biomass samples. Further,
      by quantifying the effect of biomass and relative abundance on compositional
      variability, we developed a tool for defining the expected variance in a given
      microbiome study.

PMID- 30201049
TI  - Degeneration of human photosensitive retinal ganglion cells may explain sleep and
      circadian rhythms disorders in Parkinson's disease.
AB  - Parkinson's disease (PD) patients often suffer from non-motor symptoms like sleep
      dysregulation, mood disturbances or circadian rhythms dysfunction. The melanopsin
      containing retinal ganglion cells are involved in the control and regulation of
      these processes and may be affected in PD, as other retinal and visual
      implications have been described in the disease. Number and morphology of human
      melanopsin-containing retinal ganglion cells were evaluated by
      immunohistochemistry in eyes from donors with PD or control. The Sholl number of
      intersections, the number of branches, and the number of terminals from the Sholl
      analysis were significantly reduced in PD melanopsin ganglion cells. Also, the
      density of these cells significantly decreased in PD compared to controls.
      Degeneration and impairment of the retinal melanopsin system may affect to sleep
      and circadian dysfunction reported in PD pathology, and its protection or
      stimulation may lead to better disease prospect and global quality of life of
      patients.

PMID- 30201050
TI  - Efficacy of three-dimensionally integrated exercise for scoliosis in patients
      with adolescent idiopathic scoliosis: study protocol for a randomized controlled
      trial.
AB  - BACKGROUND: Adolescent idiopathic scoliosis (AIS) is one of the most prevalent
      spinal deformities that may progress sharply during growth. The aim of this study
      will be to evaluate the efficacy of three-dimensionally integrated exercise on
      the Cobb angle, angle of trunk rotation, sagittal profile, and quality of life in
      patients with AIS. METHODS/DESIGN: The study is designed as a randomized
      controlled trial. Participants include 42 patients with AIS aged 10-16 years.
      Randomly assigned patients will follow a 6-month treatment, either in a control
      group with standard care of observation following the Scoliosis Research Society
      criteria or in an experimental group with three-dimensionally integrated exercise
      for scoliosis. Blinded assessments at baseline and immediately after intervention
      will include the change of Cobb angle, angle of trunk rotation, sagittal index,
      and quality of life. DISCUSSION: If we find that the intervention is effective in
      improving Cobb angle, angle of trunk rotation, sagittal profile, and quality of
      life in patients with AIS, this trial will have a positive impact and warrant a
      change in clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03427970
      . Registered on February 9, 2018, and revised on July 24, 2018.

PMID- 30201052
TI  - Osteoporosis of the vertebra and osteochondral remodeling of the endplate causes
      intervertebral disc degeneration in ovariectomized mice.
AB  - BACKGROUND: Studies on the relationship between osteoporosis and intervertebral
      disc degeneration (IVDD) are inconsistent. Therefore, we assessed whether IVDD is
      affected by vertebral osteoporosis in ovariectomized mice and investigated the
      underlying pathogenesis of IVDD related to osteoporosis. METHODS: Thirty healthy
      female C57BL/6 J mice aged 8 weeks were randomly divided into two groups: a
      control group (sham operation, n = 15) and an ovariectomy group (OVX; bilateral
      ovariectomy, n = 15). At 12 weeks after surgery, the bone quantity and
      microstructure in the lumbar vertebra and endplate as well as the volume of the
      L4/5 disc space were evaluated by microcomputed tomography (micro-CT). The
      occurrence and characteristic alterations of IVDD were identified via
      histopathological staining. The osteoclasts were detected using tartrate
      resistant acid phosphatase (TRAP) staining. Type II collagen (Col II), osterix
      (OSX), osteopontin (OPN), and vascular endothelial growth factor (VEGF)
      expression in the intervertebral disc were detected by immunohistochemical
      analysis. RESULTS: OVX significantly increased the body weight and decreased the
      uterus weight. Micro-CT analysis showed that osteoporosis of the vertebra and
      osteochondral remodeling of the endplate were accompanied by an increase in the
      endplate porosity and a decrease in the disc volume in the OVX group. Likewise,
      histological evaluation revealed that IVDD occurred at 12 weeks after
      ovariectomy, with features of endochondral ossification of the endplate, loose
      and broken annulus fibrosus, and degeneration of nucleus pulposus. TRAP staining
      showed that numerous active osteoclasts appeared in the subchondral bone and
      cartilaginous endplate of OVX mice, whereas osteoclasts were rarely detected in
      control mice. Immunohistochemical analysis demonstrated that the expression of
      osterix was significantly increased, notably in the endplate of OVX mice. In
      addition, Col II was decreased in the ossification endplate and the degenerative
      annulus fibrosus, where OPN and VEGF expressions were elevated in OVX mice.
      CONCLUSIONS: OVX induced vertebral osteoporosis and osteochondral remodeling of
      the cartilaginous endplate contributing to the angiogenesis and an increase in
      porosity of the bone-cartilage surface, and also affected the matrix metabolism
      which consequently had detrimental effects on the intervertebral disc. Our study
      suggests that preserving the structural integrity and the function of the
      adjacent structures, including the vertebrae and endplates, may protect the disc
      against degeneration.

PMID- 30201054
TI  - Medical and social costs after using financial incentives to improve medication
      adherence: results of a 1 year randomised controlled trial.
AB  - OBJECTIVE: Offering a financial incentive ('Money for Medication') is effective
      in improving adherence to treatment with depot antipsychotic medications. We
      investigated the cost-effectiveness in terms of medical costs and judicial
      expenses of using financial incentives to improve adherence. The effects of
      financial incentives on depot medication adherence were evaluated in a randomised
      controlled trial. Patients in the intervention group received ?30 a month over 12
      months if antipsychotic depot medication was accepted. The control group received
      mental health care as usual. For 133 patients outcomes were calculated based on
      self-reported service use and delinquent behaviour and expressed as standard unit
      costs to value resource use. RESULTS: The financial incentive resulted in higher
      average costs related to mental health care (?449.6 versus ?355.7). and lower
      medical costs related to other healthcare services (?52.0 versus ?78.4). Relevant
      differences in social costs related to delinquent behaviour were not found.
      Although wide confidence intervals indicate uncertainty, incremental cost
      effectiveness ratio's (ICER) indicate that it costs ?2080 for achieving a 20%
      increase in adherence or ?3332 for achieving over 80% adherence. In sum, offering
      money as financial incentive for increasing compliance did not lead to an overall
      cost reduction as compared to care as usual. Trial registration NTR2350, 01 June
      2010.

PMID- 30201056
TI  - Usage of the HINTS exam and neuroimaging in the assessment of peripheral vertigo
      in the emergency department.
AB  - BACKGROUND: Dizziness is a common presenting symptom in the emergency department
      (ED). The HINTS exam, a battery of bedside clinical tests, has been shown to have
      greater sensitivity than neuroimaging in ruling out stroke in patients presenting
      with acute vertigo. The present study sought to assess practice patterns in the
      assessment of patients in the ED with peripherally-originating vertigo with
      respect to utilization of HINTS and neuroimaging. METHODS: A retrospective cohort
      study was performed using data pertaining to 500 randomly selected ED visits at a
      tertiary care centre with a final diagnostic code related to peripherally
      originating vertigo between January 1, 2010 - December 31, 2014. RESULTS: A total
      of 380 patients met inclusion criteria. Of patients presenting to the ED with
      dizziness and vertigo and a final diagnosis of non-central vertigo, 139 (36.6%)
      received neuroimaging in the form of CT, CT angiography, or MRI. Of patients who
      did not undergo neuroimaging, 17 (7.1%) had a bedside HINTS exam performed.
      Almost half (44%) of documented HINTS interpretations consisted of the ambiguous
      usage of "HINTS negative" as opposed to the terminology suggested in the
      literature ("HINTS central" or "HINTS peripheral"). CONCLUSIONS: In this single
      centre retrospective review, we have demonstrated that the HINTS exam is under
      utilized in the ED as compared to neuroimaging in the assessment of patients with
      peripheral vertigo. This finding suggests that there is room for improvement in
      ED physicians' application and interpretation of the HINTS exam.

PMID- 30201057
TI  - Screening of more than 2000 Hungarian healthcare workers' anti-measles antibody
      level: results and possible population-level consequences.
AB  - Due to the European measles epidemic and the increased number of imported cases,
      it can be theorised that the risk of exposure among Hungarian healthcare workers
      (HCWs) has increased. In 2017, the increased measles circulation in the region
      led to the emergence of smaller local and hospital epidemics. Therefore, our
      objective was to determine the herd immunity in the high-risk group of HCWs. A
      hospital-based study of detecting anti-measles IgG activity was performed in 2017
      and included 2167 employees of the Military Medical Centre (Hungary). The
      screening of HCWs presented a good general seropositivity (90.6%). The highest
      seroprevalence value (99.1%) was found in the age group of 60 years or older. The
      lowest number of seropositive individuals was seen in the 41-45 years (86.2%) age
      group, indicating a significant herd immunity gap between groups. Regarding the
      Hungarian data, there might be gaps in the seroprevalence of the analysed HCWs,
      implying that susceptible HCWs may generate healthcare-associated infections.
      This study suggests that despite the extensive vaccination and high vaccine
      coverage, it is still important to monitor the level of protective antibodies in
      HCWs, or in a representative group of the whole population of Hungary, and
      possibly in other countries as well.

PMID- 30201051
TI  - TSC-associated neuropsychiatric disorders (TAND): findings from the TOSCA natural
      history study.
AB  - BACKGROUND: Most evidence for TSC-associated neuropsychiatric disorders (TAND) to
      date have come from small studies and case reports, and very little is known
      about TAND in adults. We explored baseline TAND data from the large-scale
      international TOSCA natural history study to compare childhood and adult
      patterns, describe age-based patterns, and explore genotype-TAND correlations.
      RESULTS: The study enrolled 2216 eligible participants with TSC from 170 sites
      across 31 countries at the data cut-off for the third interim analysis (data cut
      off date: September 30, 2015). The most common behavioural problems (reported in
      > 10% of participants) were overactivity, sleep difficulties, impulsivity,
      anxiety, mood swings, severe aggression, depressed mood, self-injury, and
      obsessions. Psychiatric disorders included autism spectrum disorder (ASD, 21.1%),
      attention deficit hyperactivity disorder (ADHD, 19.1%), anxiety disorder (9.7%),
      and depressive disorder (6.1%). Intelligence quotient (IQ) scores were available
      for 885 participants. Of these, 44.4% had normal IQ, while mild, moderate,
      severe, and profound degrees of intellectual disability (ID) were observed in
      28.1, 15.1, 9.3, and 3.1%, respectively. Academic difficulties were identified in
      58.6% of participants, and neuropsychological deficits (performance <5th
      percentile) in 55.7%. Significantly higher rates of overactivity and impulsivity
      were observed in children and higher rates of anxiety, depressed mood, mood
      swings, obsessions, psychosis and hallucinations were observed in adults.
      Genotype-TAND correlations showed a higher frequency of self-injury, ASD,
      academic difficulties and neuropsychological deficits in TSC2. Those with no
      mutations identified (NMI) showed a mixed pattern of TAND manifestations.
      Children and those with TSC2 had significantly higher rates of intellectual
      disability, suggesting that age and genotype comparisons should be interpreted
      with caution. CONCLUSIONS: These results emphasize the magnitude of TAND in TSC
      and the importance of evaluating for neuropsychiatric comorbidity in all children
      and adults with TSC, across TSC1 and TSC2 genotypes, as well as in those with no
      mutations identified. However, the high rates of unreported or missing TAND data
      in this study underline the fact that, even in expert centres, TAND remains
      underdiagnosed and potentially undertreated.

PMID- 30201055
TI  - Transcriptomic analysis of male and female Schistosoma mekongi adult worms.
AB  - BACKGROUND: Schistosoma mekongi is one of five major causative agents of human
      schistosomiasis and is endemic to communities along the Mekong River in southern
      Lao People's Democratic Republic (Laos) and northern Cambodia. Sporadic cases of
      schistosomiasis have been reported in travelers and immigrants who have visited
      endemic areas. Schistosoma mekongi biology and molecular biology is poorly
      understood, and few S. mekongi gene and transcript sequences are available in
      public databases. RESULTS: Transcriptome sequencing (RNA-Seq) of male and female
      S. mekongi adult worms (a total of three biological replicates for each sex) were
      analyzed and the results demonstrated that approximately 304.9 and 363.3 million
      high-quality clean reads with quality Q30 (> 90%) were obtained from male and
      female adult worms, respectively. A total of 119,604 contigs were assembled with
      an average length of 1273 nt and an N50 of 2017 nt. From the contigs, 20,798
      annotated protein sequences and 48,256 annotated transcript sequences were
      obtained using BLASTP and BLASTX searches against the UniProt Trematoda database.
      A total of 4658 and 3509 transcripts were predominantly expressed in male and
      female worms, respectively. Male-biased transcripts were mostly involved in
      structural organization while female-biased transcripts were typically involved
      in cell differentiation and egg production. Interestingly, pathway enrichment
      analysis suggested that genes involved in the phosphatidylinositol signaling
      pathway may play important roles in the cellular processes and reproductive
      systems of S. mekongi worms. CONCLUSIONS: We present comparative transcriptomic
      analyses of male and female S. mekongi adult worms, which provide a global view
      of the S. mekongi transcriptome as well as insights into differentially-expressed
      genes associated with each sex. This work provides valuable information and
      sequence resources for future studies of gene function and for ongoing whole
      genome sequencing efforts in S. mekongi.

PMID- 30201059
TI  - Risk factors associated with acute in-hospital delirium for patients diagnosed
      with a hip fracture in the emergency department.
AB  - CLINICIAN'S CAPSULE What is known about the topic? Delirium, or acute confusion,
      occurs in up to 62% of patients who have experienced a hip fracture. What did
      this study ask? What risk factors are associated with acute in-hospital delirium
      for ED patients diagnosed with a hip fracture? What did this study find? History
      of neurodegenerative disease or dementia, age>75 years, and absence of analgesia
      in the ED were associated with acute in-hospital delirium. Why does this study
      matter to clinicians? Although many variables associated with delirium may not be
      easily modified, more careful attention to ED pain management and the provision
      of better analgesia are important.

PMID- 30201060
TI  - SUITABILITY OF CURRENT EVALUATION FRAMEWORKS FOR USE IN THE HEALTH TECHNOLOGY
      ASSESSMENT OF MOBILE MEDICAL APPLICATIONS: A SYSTEMATIC REVIEW.
AB  - OBJECTIVES: To identify and appraise existing evaluation frameworks for mobile
      medical applications (MMA) and determine their suitability for use in health
      technology assessment (HTA) of these technologies. METHODS: Systematic searches
      were conducted of seven bibliographic databases to identify literature published
      between 2008 and 2016 on MMA evaluation frameworks. Frameworks were eligible if
      they were used to evaluate at least one of the HTA domains of effectiveness,
      safety, and/or cost and cost-effectiveness of an MMA. After inclusion, the
      frameworks were reviewed to determine the number and extent to which other
      elements of an HTA were addressed by the framework. RESULTS: A total of forty
      five frameworks were identified that assessed MMAs. All frameworks assessed
      whether the app was effective. Of the thirty-four frameworks that examined
      safety, only seven overtly evaluated potential harms from the MMA (e.g., the
      impact of inaccurate information). Only one framework explicitly considered a
      comparator. Technology specific domains were sporadically addressed. CONCLUSION:
      None of the evaluation frameworks could be used, unaltered, to guide the HTA of
      MMAs. To use these frameworks in HTA they would need to identify relevant
      comparators, improve assessments of harms and consider the ongoing effect of
      software updates on the safety and effectiveness of MMAs. Attention should also
      be paid to ethical issues, such as data privacy, and technology specific
      characteristics. IMPLICATIONS: Existing MMA evaluation frameworks are not
      suitable for use in HTA. Further research is needed before an MMA evaluation
      framework can be developed that will adequately inform policy makers.

PMID- 30201058
TI  - Are the Variants of the Circle of Willis Determined by Genetic or Environmental
      Factors? Results of a Twin Study and Review of the Literature.
AB  - BACKGROUND: Anatomic variants of the circle of Willis (CW) are commonly observed
      in healthy subjects. Genetic and environmental factors influencing these variants
      remain unclear. Our aim was to assess the genetic and environmental background
      affecting variant CW phenotypes. METHODS: A total of 122 adult healthy twins from
      the Hungarian Twin Registry (39 monozygotic (MZ) and 22 dizygotic (DZ) pairs,
      average age 49.7 +/- 13.4 years) underwent Time-of-Flight magnetic resonance
      angiography and transcranial Doppler sonography. We investigated the anterior and
      posterior CW according to morphological categories. Prevalence and concordance
      rates of CW variants were calculated. MZ twins discordant for CW variants were
      analyzed for cardiovascular risk factors and altered blood flow. RESULTS:
      Complete CW (45.0%) and bilaterally absent posterior communicating artery (PCoA)
      (22.5%) were the most prevalent variants in the anterior and posterior CW,
      respectively. There was no significant difference regarding the prevalence of
      variants across zygosity except for bilaterally hypoplastic PCoA (p = .02). DZ
      concordance was higher compared to MZ twins regarding morphological categories of
      the CW. Cardiovascular risk factors were not significantly associated with
      variant CW in MZ twins discordant to CW morphology. Flow parameters did not
      differ significantly among MZ twins discordant to CW variants. CONCLUSION: CW
      variants may not be determined by substantial genetic effects and are not
      influenced by altered blood flow in healthy individuals. Further investigations
      are needed to identify potential environmental factors affecting these variants.

PMID- 30201053
TI  - Effect of a combined brief narrative exposure therapy with case management versus
      treatment as usual in primary care for patients with traumatic stress sequelae
      following intensive care medicine: study protocol for a multicenter randomized
      controlled trial (PICTURE).
AB  - BACKGROUND: Traumatic events like critical illness and intensive care are threats
      to life and bodily integrity and pose a risk factor for posttraumatic stress
      disorder (PTSD). PTSD affects the quality of life and morbidity and may increase
      health-care costs. Limited access to specialist care results in PTSD patients
      being treated in primary care settings. Narrative exposure therapy (NET) is based
      on the principles of cognitive behavioral therapy and has shown positive effects
      when delivered by health-care professionals other than psychologists. The primary
      aims of the PICTURE trial (from "PTSD after ICU survival") are to investigate the
      effectiveness and applicability of NET adapted for primary care with case
      management in adults diagnosed with PTSD after intensive care. METHODS/DESIGN:
      This is an investigator-initiated, multi-center, primary care-based, randomized
      controlled two-arm parallel group, observer-blinded superiority trial conducted
      throughout Germany. In total, 340 adult patients with a total score of at least
      20 points on the posttraumatic diagnostic scale (PDS-5) 3 months after receiving
      intensive care treatment will be equally randomized to two groups: NET combined
      with case management and improved treatment as usual (iTAU). All primary care
      physicians (PCPs) involved will be instructed in the diagnosis and treatment of
      PTSD according to current German guidelines. PCPs in the iTAU group will deliver
      usual care during three consultations. In the experimental group, PCPs will
      additionally be trained to deliver an adapted version of NET (three sessions)
      supported by phone-based case management by a medical assistant. At 6 and 12
      months after randomization, structured blinded telephone interviews will assess
      patient-reported outcomes. The primary composite endpoint is the absolute change
      from baseline at month 6 in PTSD symptom severity measured by the PDS-5 total
      score, which also incorporates the death of any study patients. Secondary
      outcomes cover the domains depression, anxiety, disability, health-related
      quality-of-life, and cost-effectiveness. The principal analysis is by intention
      to treat. DISCUSSION: If the superiority of the experimental intervention over
      usual care can be demonstrated, the combination of brief NET and case management
      could be a treatment option to relieve PTSD-related symptoms and to improve
      primary care after intensive care. TRIAL REGISTRATION: ClinicalTrials.gov,
      NCT03315390 . Registered on 10 October 2017. German Clinical Trials Register,
      DRKS00012589 . Registered on 17 October 2017.

PMID- 30201061
TI  - Mental health and well-being trends among children and young people in the UK,
      1995-2014: analysis of repeated cross-sectional national health surveys.
AB  - BACKGROUND: There is a growing concern about the mental health of children and
      young people (CYP) in the UK, with increasing demand for counselling services,
      admissions for self-harm and referrals to mental health services. We investigated
      whether there have been similar recent trends in selected mental health outcomes
      among CYP in national health surveys from England, Scotland and Wales. METHODS:
      Data were analysed from 140 830 participants (4-24 years, stratified into 4-12,
      13-15, 16-24 years) in 36 national surveys in England, Scotland and Wales, 1995
      2014. Regression models were used to examine time trends in seven parent/self
      reported variables: general health, any long-standing health condition, long
      standing mental health condition; Warwick-Edinburgh Mental Wellbeing Score
      (WEMWBS), above-threshold Strengths and Difficulties Questionnaire Total (SDQT)
      score, SDQ Emotion (SDQE) score, General Health Questionnaire (GHQ) score.
      RESULTS: Across all participants aged 4-24, long-standing mental health
      conditions increased in England (0.8-4.8% over 19 years), Scotland (2.3-6.0%, 11
      years) and Wales (2.6-4.1%, 7 years) (all p < 0.001). Among young children (4-12
      years), the proportion reporting high SDQT and SDQE scores decreased
      significantly among both boys and girls in England [SDQE: odds ratio (OR) 0.97
      (0.96-0.98), p < 0.001] and girls in Scotland [SDQE: OR 0.96 (0.93-0.99), p =
      0.005]. The proportion with high SDQE scores (13-15 years) decreased in England
      [OR 0.98 (0.96-0.99), p = 0.006] but increased in Wales [OR 1.07 (1.03-1.10), p <
      0.001]. The proportion with high GHQ scores decreased among English women (16-24
      years) [OR 0.98 (0.98-0.99), p = 0.002]. CONCLUSIONS: Despite a striking increase
      in the reported prevalence of long-standing mental health conditions among UK
      CYP, there was relatively little change in questionnaire scores reflecting
      psychological distress and emotional well-being.

PMID- 30201062
TI  - RAGE in Cancer Lung: the End of a Long and Winding Road is in Sight.

PMID- 30201063
TI  - Helicobacter Pylori Infection and Lung Cancer: ?New Insights and Future
      Challenges.
AB  - Helicobacter pylori (H. pylori) is the causative agent of chronic gastritis and
      peptic ulcer diseases and is an important risk factor for the development
      functional dyspepsia, peptic ulceration, gastric adenocarcinoma and mucosa
      associated lymphoid tissue lymphoma. H. pylori has very high rates of infection
      in human populations, and it is estimated that over 50% of the world population
      is infected. Recently, certain extra-gastric manifestations, linked to H. pylori
      infection, have been widely investigated. Noteworthy, a growing body of evidences
      supports an association between H. pylori infection with lung cancer. The present
      review intend to highlight not only the most recent evidences supporting this
      association, but also some missed points, which must be considered to validate
      this emerging association.

PMID- 30201064
TI  - [Formulation and Efficacy of Liposome-encapsulated Afatinib for Therapy of Non
      small Cell Lung Cancer].
AB  - BACKGROUND: Afatinib, a second-generation irreversible epidermal growth factor
      inhibitor receptor for the development of non-small cell lung cancer and
      secondary drug resistance, has low bioavailability and adverse reactions due to
      current oral administration. The aim of this study was to prepare a novel drug
      delivery system, afatinib liposome, and to establish a method for the
      determination of encapsulation efficiency. METHODS: Four different preparation
      methods were used to prepare afatinib liposomes, and the optimal preparation
      process was determined by comparing the encapsulation efficiency and particle
      size. RESULTS: It has been verified that sephadex microcolumn centrifugation can
      be used to purify afatinib liposomes, and UV spectrophotometry can be employed to
      determine the entrapment efficiency of liposomes. Among different preparation
      methods, the encapsulation efficiency of afatinib liposomes prepared by ammonium
      sulfate gradient method was 90.73% and the average particle size was 108.6 nm.
      CONCLUSIONS: Ammonium sulfate gradient method can be successfully applied to
      prepare afatinib liposomes that performed higher encapsulation efficiency and
      smaller particle size. The UV spectrophotometry employed to determine the
      liposome encapsulation efficiency was easy operation and with high accuracy.

PMID- 30201065
TI  - [Endobronchial Ultrasound Guided Transbronchial Needle Aspiration for The
      Diagnosis and Genotyping of Lung Cancer].
AB  - BACKGROUND: Endobronchial ultrasound guided transbronchial needle aspiration
      (EBUS-TBNA) has emerged as an innovative technique for diagnosis and staging of
      lung cancer. But whether the procedure can provide enough tissue for the
      detection of gene mutations is still to be defined. Here we evaluated the
      efficacy of lung cancer diagnosis and gene analysis using samples obtain via EBUS
      TBNA. METHODS: Patients with suspected lung cancer and mediastinal lesions were
      referred for EBUS-TBNA. Diagnosis and sub-classifications were made by
      pathologists. Samples with non-squamous non small cell lung cancer sub type were
      tested for the EGFR and/or ALK mutations. RESULTS: A total of 377 patients were
      included in this study. The median needle passes were 2.07. Lung cancer was
      diagnosed in 213 patients. The diagnosis accuracy for malignancy was 92%.
      Epidermal growth factor receptor (EGFR) mutations, anaplasticlymphoma kinase
      (ALK) fusion genes and double genes analysis were successfully preformed in 84
      (90%), 105 (95%) and 79 (90%) patients. The number of needle passes and the
      diameters of lymph node were not associated with the efficacy of gene testing in
      univariate analysis. However, samples of adenocarcinoma sub type showed a
      tendency associated with higher genotyping efficacy. CONCLUSIONS: Tissue samples
      obtained through EBUS-TBNA are sufficient for pathological diagnosis and genetic
      analysis of lung cancer. The pathology type of sample affected genotyping
      efficacy.

PMID- 30201066
TI  - [Expression and Significance of ACIN1 mRNA in Platelets of Lung Cancer].
AB  - BACKGROUND: During the occurring and developing of tumor, tumor-educated
      platelets mRNA profiles were altered. Since platelets are anuclear, the level of
      mRNAs is probably post-transcriptional regulated by the splicing maturation of
      pre-mRNA and alternative splicing. Apoptotic chromatin condensation inducer 1
      (ACIN1) has been shown to be a component of a splicing-dependent multiprotein
      exon junction complex (EJC) and was involved in mRNA metabolism associated with
      splicing. This study analyzed the expression of ACIN1 mRNA in platelets, and
      explored its potential as a biomarker of lung cancer. METHODS: 156 patients with
      lung cancer and 58 healthy controls in Shandong Cancer Hospital were collected.
      We isolated platelet pellets by low-speed centrifugation and extracted total RNA.
      The expression of ACIN1 mRNA in platelets was detected by RT-PCR, the results
      were analyzed statistically. And the relationship between expression of ACIN1
      mRNA and clinical factors were also analyzed. RESULTS: The expression level of
      ACIN1 mRNA in platelets of patients with lung cancer was significantly higher
      than that in platelets of healthy controls (P=0.015). The ROC curve showed that
      the area under the curve of ACIN1 mRNA for detecting lung cancer were 0.608. The
      expression of ACIN1 mRNA in platelets of lung cancer has no significant
      relationship with age, gender, pathological type and metastasis or not (P>0.05).
      CONCLUSIONS: ACIN1 mRNA was highly expressed in platelets of lung cancer
      patients, and the detection of its expression level might have potential clinical
      value for the diagnosis of lung cancer.

PMID- 30201067
TI  - [Analysis of Percutaneous Biopsy of 41 Small Lung Lesions].
AB  - BACKGROUND: When lung cancer screening work extensively developed in recent
      years, more and more small lung lesions were found in clinic. The aim of this
      study is to analysis computed tomography (CT) guided percutaneous biopsy for lung
      small lesions (diameter<2 cm) on results, complications and prognosis. METHODS:
      Choose CT guided percutaneous lung biopsy were performed in 41 cases of pulmonary
      peripheral lesions, single lesion in 39 cases, multiple lesions in 2 cases, 5-20
      (13.1+/-5.2) mm in maximum diameter, depth from lung surface 1-45 (16.5+/-13.7)
      mm, ground-glass opacity (GGO) components 0%-100% (66.8%+/-35.2%). RESULTS: 41
      patients and 43 biopsies successfully obtained pathological tissue. Atypical
      adenomatous hyperplasia in 3 cases, squamous carcinoma in 1 case, adenocarcinoma
      in 37 cases( carcinoma in situ in 7 cases, micro-invasive carcinoma in 5 cases,
      invasive adenocarcinoma in 25 cases, double primary lung cancer in 2 cases),
      inflammatory lesions in 2 cases. Except 2 cases of inflammatory lesions are in
      follow-up, biopsy and surgical pathology alignment (specificity) was 100%. 41
      patients occurred complications related to percutaneous biopsy. Pneumothorax were
      in 22 cases, drainage required in 2 cases. There were 17 cases with hemoptysis,
      accounting for 39.5% incidence are self-limited. Intracranial air embolism
      occurred in 2 cases by 4.6% incidence. They were fully recovered. CONCLUSIONS:
      For small lung lesions, CT guided percutaneous biopsy is technically feasible.
      However, for small lung lesions especially pure GGO biopsy, it is still need to
      be cautious.

PMID- 30201068
TI  - [Advances in Double Mutations of EGFR and ALK Gene in Non-small Cell Lung
      Cancer].
AB  - Molecular target therapy is one of the most popular field of non-small cell lung
      cancer (NSCLC) treatmnet. Epidermal growth factor receptor (EGFR) mutation and
      anaplastic lymphoma kinase (ALK) rearragement are the most important two
      oncogenic drivers in NSCLC, early studies suggested that EGFR mutations and ALK
      rearrangements are mutually exclusive, but isolated cases or small sample
      research with concomitant EGFR and ALK alterations have been constantly reported.
      The co-occurrence of EGFR mutations and anaplastic lymphoma kinase (ALK)
      rearrangements constitutes a rare molecular, the frequency of EGFR/ALK co
      alterations was about 1%, however, little has been known about clinicopathologic
      feature and treatment. This review summarized published case report, EGFR and ALK
      alterations are common in female, Asian origin, never smoker, IV stage, and
      denocarcinomas. First-line treatment can choose EGFR or ALK tyrosine kinase
      inhibitors (TKIs). However, studies about the origin and resistance mechanism in
      EGFR/ALK co-alterations are little, require more experimental and clinical
      research.?.

PMID- 30201070
TI  - [Predictive Markers for Treating Efficacy of PD-1/PD-L1 Inhibitors in Patients
      with Lung Cancer: A Review of the 18th World Conference on Lung Cancer].
AB  - Programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) checkpoint
      blockades have dramatically changed the treatment of non-small cell lung cancer
      (NSCLC). But we still have no definite biomarkers that may predict the efficacy
      of treatment by PD-1/PD-L1 inhibitors. In the 18th World Conference on Lung
      Cancer, the biomarkers that may predict the efficacy of treatment by PD-1/PD-L1
      inhibitors in patients with lung cancer has been a popular topic, and it has huge
      potential in the future. In order to enable more patients to get more benefits
      from treatment, researchers are looking forward to finding the optimum
      biomarkers. By organizing and summarizing the information about the biomarkers
      predicting PD-1/PD-L1 in patients with lung cancer, this review mainly focused on
      the following six aspects to introduce: expression of PD-L1; tumor mutational
      burden and the ability of mutation repair, malignant tumor driver mutation,
      biomarker of immunological effect, blood cell account, comprehensive analysis
      model. We are hoping to help doctors to find the best biomarker, then much more
      lung cancer patients could obtain antitumor effects in PD-1/PD-L1 inhibitors
      treatment.?.

PMID- 30201069
TI  - [Advances in Surgical Approach and Resection of Non-small Cell Lung Cancer].
AB  - With the change of the spectrum of disease, the incidence and mortality of non
      small cell lung cancer (NSCLC) has been high in global scale, since surgical
      intervention was applied to treat lung cancer, its status is increasing day by
      day, at present comprehensive treatment leaded by surgery has become the
      preferred scheme for NSCLC, there are many different kinds of surgical approaches
      and operation methods of disease, and the new technologies appear constantly, the
      paper aim to summarize the research progress of different operationmethods and
      surgical approach. With the development of software and hardware technology and
      the concept of minimally invasive thoracoscopic surgery was received by more
      people, minimally invasive thoracoscopic surgery has brought more benifit than
      traditional thoracotomy for lung cancer patients, minimally invasive
      thoracoscopic surgery reserve more lung tissue and improve the survival quality
      of patients due to better pulmonary function, we believe that minimally invasive
      thoracoscopic surgery can bring more benefits to people with surgical indications
      and surgical procedure further standardization.?.

PMID- 30201071
TI  - [Current Status for Anaplastic Lymphoma Kinase in Non-small Cell Lung Cancer].
AB  - The incidence of ALK gene rearrangement in non-small cell lung cancer (NSCLC) was
      about 3% to 5%. ALK gene inhibitors have made great breakthrough in recent years,
      significantly extending the survival period of patients with ALK(+) advanced
      NSCLC. But the majority of patients will be acquired drug resistance after
      treatment. This article has been explained separately from the ALK genetic
      background, the detection method, the treatment of the three generations of ALK
      inhibitors and the strategy after drug resistance. It is desire to have reference
      value and reference meaning for clinical work.?.

PMID- 30201072
TI  - [Advances on Recognizing and Managing Tumor Heterogeneity].
AB  - Tumor heterogeneity is one of the characteristics of malignant tumors, which can
      cause differences in tumor growth rate, invasion, migration, drug sensitivity and
      prognosis. Discoveries and development upon on tumor-driver genes and targeted
      therapy paved the way on dealing with cancer diagnosis and treatment. However,
      the existence of tumor heterogeneity makes malignant tumor more hardly to
      overcome. It is generally present and far more complicated during the process of
      cancer recurrence, development and evolution. Thus, it has becoming key areas in
      precision medicine regarding to designing optimal therapeutic approaches
      targeting the mechanisms and phenotypes of tumor heterogeneity, based on novel
      detecting techniques and new concepts and theory. This review summarized the
      current references on tumor heterogeneity, in order to better understand the
      function and mechanisms, and eventually manage tumor heterogeneity through
      various methods.?.

PMID- 30201073
TI  - [Latest Progress of Intraoperative Pleural Lavage Cytology in Lung Cancer
      Surgery].
AB  - Intraoperative pleural lavage cytology is a diagnostic technique used to detect
      tumor cells and serve as a prognostic parameter for non-small cell lung cancer
      (NSCLC) patients. In the past several decades, many scholars have been dedicated
      to clarifying the relationships between positive intraoperative pleural lavage
      cytology results and postoperative survival as well as tumor recurrence and
      metastasis. However, the findings remained various due to the inhomogeneity of
      different research. It has been confirmed that a positive intraoperative pleural
      lavage cytology result is one of the risk factors for the prognosis of
      postoperative patients. This study reviewed the advances in research of
      intraoperative pleural lavage cytology in recent years from several aspects,
      including clinical significance, influencing factors and possible mechanisms.?.

PMID- 30201074
TI  - [MicroRNA and Lung Cancer: A Mini Review].
AB  - MicroRNAs (miRNAs) a class of non-coding RNAs about 22 nt in size that are found
      in a wide range of organisms from plants, viruses to humans. MicroRNA has a wide
      range of biological functions. It can recruit related RNA enzymes and lead to
      mRNA degradation after binding to mRNA specificity, thus blocking the expression
      of protein encoding genes and then affecting their biological functions. In
      recent years, microRNA has been found to be closely related to the biological
      behaviors, such as the occurrence, development, invasion and metastasis of
      multiple human malignant carcinomas, and play a regulatory role in the above
      biological phenotypes. Lung cancer is the highest incidence of malignancy. The
      exact molecular mechanism of its occurrence and development has not been fully
      elucidated. Previous studies have shown that microRNA plays an important role in
      lung tumor suppressor gene inactivation, oncogene activation and epigenetics. At
      the same time, there are also reports that there is a significant difference in
      the expression of microRNA in patients with lung cancer and benign lung diseases.
      This differential expression provides a basis for the feasibility of microRNA as
      a diagnostic and pre biological marker for lung cancer.?.

PMID- 30201075
TI  - Evaluation of early and late-term infections after renal transplantation:
      Clinical experiences of Sanko University Medical Faculty Transplantation Center.
AB  - OBJECTIVE: Infections play an important part in post-transplantation causes of
      morbidity and mortality. The purpose of this study is to evaluate short-, and
      long-term infections encountered in after renal transplantations. MATERIAL AND
      METHODS: Two hundred and thirteen cases that consisted of both living and cadaver
      donors, who suffered from late period renal insufficiency and had renal
      transplant between June 2011 and January 2016 at the Transplantation Center of
      Sanko University School of Medicine were included in the study. In this study the
      short-, and long-term infections seen in post renal transplantation were examined
      retrospectively. Infection types, frequency and periods of infection, infection
      agents and predisposing factors were determined as the examination parameters.
      RESULTS: Of the 213 patients who received renal transplant, 139 were males
      (65.3%) and 74 were women (34.75%) and the mean age was 42+/-11,8 (range, 14-70)
      years. Twelve (5.6%) patients exited after renal transplantation. Post-transplant
      infections were seen in 49 patients (23.1%) within 1-6 months; in 13 patients
      (6.1%) within 6-12 months; and in 5 patients (2.4%) after the 12th month. The
      most common infections after renal transplantation were associated with urinary
      tract (70 patients, 34.3%). The most frequently isolated agents were E. coli
      (n=66; 30.9%), Kebsiella spp. (n=18; 8.4%) and Enterococci (n=18; 8.4%)
      respectively. The renal transplants from the cadavers were observed to contract
      infections 1.78 times more frequently compared to the living donors (OR=1.78, 95%
      CI=1.03-3.09). CONCLUSION: The most common complication after renal
      transplantation are infections. The majority of the infections are seen within
      the first year especially between 1-6 months. Post-transplant infections are
      often related to urinary system. E.coli is the most frequently isolated agent and
      it may be responsible for urosepsis in renal transplant patients. Infection more
      often seen in renal transplantations from cadavers.

PMID- 30201076
TI  - Our experience with ureterocystoplasty in bilateral functional kidneys.
AB  - OBJECTIVE: We have reviewed the data of the patients in order to evaluate the
      effectiveness of our ureterocystoplasty technique in augmentation cystoplasty
      operation. MATERIAL AND METHODS: Data of a total of 16 patients with bilateral
      functional kidneys who had undergone augmentation ureterocystoplasty between
      January 1995 and June 2018 which were retrieved during the retrospective archive
      scanning were included in the study. Ultrasonography (USG), serum blood urea
      nitrogen and creatinine values and Technetium-99 DTPA (Tc-99 DTPA) scan were used
      to evaluate the renal function of the patients. Intravenous pyelography (IVP) and
      USG were used to evaluate the ureters before surgery. Magnetic resonance (MR)
      urographies were performed in our center. RESULTS: Of the total 16 patients, 10
      were male and 6 were female, while ages ranged from 1 to 24 years. Among 16
      patients, the most common cause of neurogenic bladder etiology was
      meningomyelocele. In the urodynamic studies performed before the operation, it
      was determined that the bladder capacities of the patients were between 40-180 mL
      and the bladder compliances were 1.0-4.0 cc/cmH2O. At postoperative 3rd months,
      it was determined that the bladder capacities of the patients were between 180
      330 mL and the bladder compliances were between 6.0-24.0 cc/cmH2O. CONCLUSION:
      Augmentation ureterocystoplasty seems to be an appropriate technique in which
      successful results are obtained with appropriate patient selection. Besides,
      complications that may occur due to use of ileal segment are avoided.

PMID- 30201077
TI  - The influence of metabolic profile of obese men on the severity of erectile
      dysfunction: are metabolically healthy obese individuals protected?
AB  - OBJECTIVE: To determine the prevalence of erectile dysfunction (ED) in
      metabolically healthy obese (MHO) individuals, and to compare ED severity and
      hypogonadism prevalence in MHO, metabolically unhealthy obese (MUO) and
      metabolically healthy non-obese individuals. MATERIAL AND METHODS: ED patients
      (n=460) were evaluated by standardized protocol, that included clinical
      evaluation, abridged 5-item version of the International Index of Erectile
      Function (IIEF-5) questionnaire survey, and Penile Duplex Doppler Ultrasound
      (PDDU) exam. Patients were classified as obese [body mass index (BMI) >=30.0
      kg/m2] and non-obese (BMI <30.0 kg/m2), and metabolic health status was defined
      by National Cholesterol Education Program Adult Treatment Panel III (NCEP ATPIII)
      criteria. Statistical analysis was performed and statistical significance was
      considered at p-level <0.05. RESULTS: The mean age of the subjects was 56.2+/
      10.5 years. MHO was present in 40% of obese individuals (n=37). MUO had lower
      mean peak systolic velocity (mPSV) compared to MHO (28.1 cm/s vs. 36.9 cm/s;
      p=0.005), and IIEF-5 scores were also lower in MUO compared to MHO patients (10.2
      vs. 13.1; p=0.018). No statistical differences in IIEF-5 score, mPSV and
      hypogonadism prevalence between MHO and metabolically healthy non-obese (MHNO)
      patients were observed. CONCLUSION: Our results lead us to conclude that healthy
      metabolic profile protects obese individuals from severity of ED. The strong
      association between obesity and ED may be otherwise attributed to metabolic
      abnormalities present in the obese.

PMID- 30201079
TI  - Is there a difference in the number of interstitial cells, neurons, presence of
      fibrosis and inflammation in ureteropelvic junction tissues of patients with
      ureteropelvic junction obstruction with and without crossing vessels?
AB  - OBJECTIVE: We compared the number of interstitial cells (ICs), nerves, presence
      of fibrosis and inflammation at the level of full-thickness human ureteropelvic
      junction (UPJ) tissues obtained from normal subjects, and patients with UPJ
      obstruction with and without crossing vessels. MATERIAL AND METHODS: Normal UPJ
      tissues (n=12) histopathologically confirmed to be without tumor involvement were
      obtained from subjects who underwent radical nephrectomy for kidney mass.
      Additional UPJ tissues were obtained from patients who underwent pyeloplasty due
      to UPJ obstruction. Crossing vessel was identified in 17 patients. In 57
      patients, no crossing-vessel was noted. ICs were stained immunohistochemically
      with anti-human CD117 (c-kit) antibody. Neural tissue was stained with S-100. The
      numbers of ICs and neurons were compared between the groups: controls with normal
      UPJ (Group I), Ureteropelvic junction obtruction (UPJO) with crossing vessel
      (Group II) and UPJ obstruction without crossing vessel (Group III). Groups were
      also compared in terms of the presence of fibrosis and inflammation. RESULTS: The
      mean age of total population included in the study was 30.5+/-18.5 years. No
      significant differences were detected between the three groups regarding mean and
      median numbers of ICs at the level of UPJ (lamina propria and muscle layer) and
      mean and median numbers of neurons at the level of lamina propria (p>0.05).
      Likewise, no significant differences were detected between the three groups
      regarding the presence of fibrosis and inflammation (p>0.05). CONCLUSION: Number
      of ICs, neurons, presence of fibrosis and inflammation seem to be similar in the
      intact UPJ and UPJ with obstruction with and without crossing vessel. Cellular
      function rather than the number ICs might play a role that warrants further
      research.

PMID- 30201080
TI  - Small renal pelvis stones: Shock wave lithotripsy or flexible ureteroscopy? A
      match-pair analysis.
AB  - OBJECTIVE: Kidney stones in renal pelvis may be treated using various methods.
      For larger stones, percutaneous nephrolitotomy (PNL) is the first choice of
      option; where for smaller stones, shock wave lithotripsy (SWL) or flexible
      ureteroscopy (F-URS) could be more suitable options. In this article we aimed to
      compare the outcomes of F-URS and SWL on the treatment of renal pelvis stones <10
      mm. MATERIAL AND METHODS: Files of patients treated with SWL and F-URS for renal
      pelvis stones <10 mm between March 2013 and May 2016 in our clinic were analyzed.
      For comparison, a match-pair analysis was designed. Complete stone removal was
      considered success. RESULTS: Forty patients were treated using F-URS (Group 1)
      and 40 patients underwent SWL (Group 2). Patients were assessed the day after the
      last session of the procedure. The early stone-free rates were 70% (28/40) in
      Group 1, and 15% in Group 2 (p<0.05). The same analysis was performed after three
      months. Stone-free rates were 100% and 92.5% in Groups 1 and 2, respectively
      (p=0.079). Three patients in Group 2 were not stone free after 3 sessions of SWL
      and considered unsuccessful. They were all successfully treated by F-URS.
      CONCLUSION: Even though there is no statistical difference among groups, our data
      may be interpreted as having better outcomes and tolerability with F-URS than
      SWL. We believe F-URS may have a great treatment prospect in this particular
      patient group.

PMID- 30201078
TI  - Kidneys with small renal masses: Can they be utilized for kidney transplantation
      in the era of partial nephrectomy?
AB  - OBJECTIVE: To retrospectively evaluate our database to determine our partial
      nephrectomy and radical nephrectomy rates and to see percentage of the discarded
      kidneys which were suitable for transplantation after radical nephrectomy.
      MATERIAL AND METHODS: Patients who underwent radical or partial nephrectomy
      between January 2000 and December 2016 were identified. Only stage I tumors
      according to tumor, node, metastasis classification were included in this review.
      Tumor size, location, proximity to renal collecting system and hilum were
      considered while deciding the suitability of a kidney for transplantation.
      RESULTS: A statistically significant gradual increase in the number of patients
      treated with partial nephrectomy was observed (p=0.00001). Only 17 out of 181
      kidneys with a tumor size smaller than 3 cm could be an appropriate candidate for
      a renal transplantation if they were to be transplanted. CONCLUSION: Exact number
      of the discarded kidneys with small renal masses which can be used for kidney
      transplantation should be determined by large scale studies. A national or
      governmental policy may only be developed to utilize these discarded organs after
      the magnitude of the wasted kidneys can be determined.

PMID- 30201083
TI  - Efficacy of topical tranexamic acid within a blood-saving programme for primary
      total hip arthroplasty: a pragmatic, open-label randomised study.
AB  - BACKGROUND: Total hip arthroplasty entails considerable peri-operative blood
      loss, which may lead to acute post-operative anaemia and red blood cell
      transfusion. This study was aimed at assessing whether the addition of topical
      tranexamic acid to our ongoing blood-saving protocol for total hip arthroplasty
      was effective and safe. MATERIALS AND METHODS: A pragmatic, prospective, open
      label randomised study of patients scheduled for total hip arthroplasty at a
      single centre was conducted. Consecutive patients were randomly assigned to
      receive topical tranexamic acid (2 g) at the end of surgery (tranexamic group,
      n=125) or not (control group, n=129). A restrictive transfusion protocol was
      applied. Outcome measures were red blood cell loss at 24 hours after surgery, in
      hospital transfusion rate, and incidence of thromboembolic complications.
      RESULTS: Topical tranexamic acid was effective in reducing both red cell loss
      (mean difference: 138 mL [95% CI 87-189 mL]; p<0.001) in the 24h after surgery
      and in-hospital transfusion rates (12 vs 32.6%, for the tranexamic acid and
      control groups, respectively; p<0.001; relative risk=0.37 [95% CI 0.22-0.63]).
      However, relative red cell loss and transfusion rates were higher in females than
      in males, irrespectively of tranexamic acid use. The beneficial effect of
      tranexamic acid on transfusion was restricted to patients with pre-operative
      haemoglobin >=13 g/dL (5.1 vs 24.8%; p<0.001). Topical tranexamic acid was well
      tolerated and no clinically apparent thromboembolic complications were witnessed.
      DISCUSSION: The use of topical tranexamic acid after hip arthroplasty reduced red
      cell loss and transfusion rates; the efficacy of this strategy may be improved by
      reinforcing both pre-operative haemoglobin optimisation and adherence to the
      practice of transfusing single units of red cells.

PMID- 30201085
TI  - Influence of apheresis collection device and container on the storage properties
      of platelets in 90% PAS-5/10% plasma.
AB  - BACKGROUND: The storage properties of apheresis platelets suspended in the
      experimental additive solution PAS-5 and 10% plasma may be affected by the
      collection instrument or storage container. METHODS AND EXPERIMENTAL DESIGN: The
      same consenting 12 donors provided A or T platelets with concurrent plasma on
      four occasions in 100% plasma. Following collection and resting, the platelets
      were centrifuged, and plasma was expressed and resuspended in PAS-5 to yield
      units with 10% plasma. Platelets were either maintained in the original storage
      container or transferred to another of the manufacturer's storage containers. On
      days 1, 5 and 7, units were assayed for an array of in vitro tests. RESULTS:
      Average unit volume, yield and percent plasma was 291+/-11 mL, 3.7+/-0.4*1011,
      and 10.3+/-0.7%, respectively, and were comparable between collections with
      either of the apheresis instruments and stored with either of the manufacturer's
      containers. Day 1 platelet activation (CD62P+) was 40+/-22% and was similar in
      either of the collection instruments or containers. Except for pH (days 1, 5),
      CO2 (days 1, 5, 7), and extent of shape change (day 5), every other in vitro
      parameter was similar between apheresis platforms or the manufacturer's
      container. pH values of all units on all days of storage were >=6.8, except one
      unit that was collected on T and stored in an A container, which had pH values of
      6.8 and 5.7 on days 5 and 7, respectively. DISCUSSION: Storage of platelets
      suspended in PAS-5 with 10% plasma is feasible in the original manufacturer's
      container for seven days. Based on CO2 levels, T containers have greater gas
      exchange than A containers.

PMID- 30201081
TI  - Budget impact of implementing platelet pathogen reduction into the Italian blood
      transfusion system.
AB  - BACKGROUND: Despite improvements in blood donor selection and screening
      procedures, transfusion recipients can still develop complications related to
      infections by known and emerging pathogens. Pathogen reduction technologies (PRT)
      have been developed to reduce such risks. The present study, developed whithin a
      wider health technology assessment (HTA) process, was undertaken to estimate the
      costs of the continuing increase in the use of platelet PRT in Italy. MATERIALS
      AND METHODS: A multidisciplinary team was established to perform the HTA and
      conduct a budget impact analysis. Quantitative data on platelet use were derived
      from the 2015 national blood transfusion report and from the Italian Platelets
      Transfusion Assessment Study (IPTAS). The current national fee of 60 Euro per
      platelet PRT procedure was used to quantify the costs to the Italian National
      Health Service (INHS). The analysis adopts a 3-year time-frame. In order to
      identify the impact on budget we compared a scenario representing an increased
      use of PRT platelets over time with a control scenario in which standard
      platelets are used. RESULTS: Progressive implementation of PRT for 20%, 40% and
      66% of annual adult platelet doses could generate an increase in annual costs for
      the INHS amounting to approximately 7, 14 and 23 million Euros, respectively. Use
      of kits and devices suitable for the treatment of multiple adult platelet doses
      in one PRT procedure could lower costs. DISCUSSION: In order to fully evaluate
      the societal perspective of implementing platelet PRT, the increase in costs must
      be balanced against the expected benefits (prevention of transfusion
      transmissible infections, white cell inactivation, extension of platelet storage,
      discontinuation of pathogen detection testing). Further studies based on actual
      numbers of platelet transfusion complications and their societal cost at a local
      level are needed to see the full cost to benefit ratio of platelet PRT
      implementation in Italy, and to promote equal treatment for all citizens.

PMID- 30201084
TI  - Factors affecting the quality, safety and marketing approval of clotting factor
      concentrates for haemophilia.
AB  - Selecting therapeutic products for the treatment of haemophilia follows the
      process of obtaining market approval of products submitted to the scrutiny of a
      regulatory agency. In well-resourced countries, key decisions on whether a
      product is sufficiently safe and of high quality are made by highly expert and
      well-resourced agencies, such as the US Food and Drug Administration (FDA) and
      the European Medicines Agency (EMA). In countries lacking such agencies, well
      informed decisions can still be made through an appreciation of the key issues
      affecting the quality, safety and efficacy of haemophilia products. A number of
      well-established principles may then be applied in order to make a choice. In
      this review, reflecting principles outlined by the World Federation of
      Hemophilia, we outline the key features in determining the acceptability of
      therapeutic products for haemophilia in order to ensure an optimal choice in all
      the environments providing haemophilia care.

PMID- 30201082
TI  - Efficacy of platelet-rich plasma as conservative treatment in orthopaedics: a
      systematic review and meta-analysis.
AB  - BACKGROUND: The aim of this systematic review and meta-analysis was to evaluate
      the benefit of platelet-rich plasma (PRP) in non-surgical orthopaedic procedures.
      MATERIAL AND METHODS: We searched the Cochrane Wounds Specialized Register,
      CENTRAL, MEDLINE (through PUBMED), Embase, and SCOPUS. We also searched clinical
      trials registries for ongoing and unpublished studies and checked reference lists
      to identify additional studies. RESULTS: We found 36 randomised controlled trials
      (2,073 patients) that met our inclusion criteria. The included studies mostly had
      small numbers of participants (from 20 to 225). Twenty-eight studies included
      patients with lateral epicondylitis or plantar fasciitis. PRP was compared to
      local steroids injection (19 studies), saline injection (6 studies), autologous
      whole blood (4 studies), local anaesthetic injection (3 studies), dry needling
      injection (3 studies), and to other comparators (4 studies). Primary outcomes
      were pain and function scores, and adverse events. On average, it is unclear
      whether or not use of PRP compared to controls reduces pain scores and functional
      score at short- (up to 3 months) and medium- (4-6 months) term follow-up. The
      available evidence for all the comparisons was rated as very low quality due to
      inconsistency, imprecision, and risk of bias in most of the selected studies.
      There were no serious adverse events related to PRP injection or control
      treatments. CONCLUSIONS: The results of this meta-analysis, which documents the
      very marginal effectiveness of PRP compared to controls, does not support the use
      of PRP as conservative treatment in orthopaedics.

PMID- 30201086
TI  - Molecular genetic analysis of weak ABO subgroups in the Chinese population
      reveals ten novel ABO subgroup alleles.
AB  - BACKGROUND: A weak ABO subgroup is one of the most important causes of an ABO
      blood grouping discrepancy. Here, we investigated the distribution of weak ABO
      subgroups in the Chinese population and identified ten novel weak ABO subgroup
      alleles. MATERIAL AND METHODS: We performed phenotype investigations by
      serological studies, analysed the DNA sequence of the ABO gene by direct
      sequencing or sequencing after cloning, and evaluated the role of
      glycosyltransferase mutations by in silico analysis and in vitro expression
      assay. RESULTS: Three hundred and fifty-one individuals with a weak ABO subgroup
      were detected among 1.45 million blood-typed subjects. Ten novel weak ABO
      subgroup alleles were identified. Molecular modelling and analysis of GTA
      mutation p.L339P suggested that the mutation may change the local conformation of
      GTA and reduce its stability. The in vitro expression assay showed that A antigen
      expression and agglutination of HeLa cells transfected with GTA mutant p.L339P
      decreased significantly compared to those of cells transfected with wild-type
      GTA. CONCLUSION: Ten novel weak ABO subgroup alleles were identified in the
      Chinese population. GTA mutant p.L339P may lead to a weak A phenotype by changing
      the local conformation of GTA and reducing its stability.

PMID- 30201087
TI  - Urate-Lowering Therapy in Moderate to Severe Chronic Kidney Disease.
AB  - CONTEXT: Hyperuricemia is an independent risk factor for progression of kidney
      disease. OBJECTIVE: To determine whether lowering serum uric acid level (sUA) to
      below 6 mg/dL (target) improves mild to moderate chronic kidney disease (CKD) and
      whether CKD stage influences the benefit of lowering sUA to target. DESIGN:
      Retrospective epidemiologic cohort study conducted over 8 years. Estimated
      glomerular filtration rate (eGFR) was required in the 6 months preceding the
      index date (defined as first occurrence of sUA < 7 mg/dL), and at least 1 sUA and
      eGFR were required during follow-up. Patients were urate-lowering therapy (ULT)
      naive, aged 18 years or older, and had CKD Stages 2 to 4 at baseline. Health Plan
      enrollment with drug benefit was required. Exclusions included active cancer,
      dialysis, or other kidney disease. MAIN OUTCOME MEASURES: A 30% decrease or 30%
      improvement in eGFR from baseline. RESULTS: A total of 12,751 patients met
      inclusion criteria; 2690 patients received ULT during follow-up and 10,061 did
      not. Target sUA was achieved in 1118 patients (42%) receiving ULT. A 30%
      improvement in eGFR was likelier in patients who achieved the target (odds ratio
      [OR] = 1.78, p < 0.001). Pairwise comparison of CKD stages showed a 30%
      improvement in eGFR in CKD Stage 2 (OR = 2.26, p = 0.017) and Stage 3 (OR = 2.23,
      p < 0.001) but not Stage 4 (OR = 1.50, p = 0.081). CONCLUSION: Patients who
      achieve an American College of Rheumatology target sUA below 6 mg/dL during ULT
      have higher rates of eGFR improvement, especially in CKD Stages 2 and 3.

PMID- 30201089
TI  - Sensory Inattention.

PMID- 30201090
TI  - "A" for Life.
AB  - This is a story of a medical intern whose cascade of baffling thoughts about
      pursuing a career finally led to a gratifying conclusion. This young intern is
      easily swayed by the opinions of others, but circumstances proved that the field
      he chose was the one he was made for. This is a story of determination and belief
      in one's ability, which gave the power to fight against the odds.

PMID- 30201088
TI  - Clostridium Difficile-Associated Infection in Trauma Patients: Development of the
      Clostridium Difficile Influencing Factors (CDIF) Score.
AB  - CONTEXT: Clostridium difficile-associated infection (CDAI) can result in longer
      hospitalization, increased morbidity, and higher mortality rates for surgical
      patients. The impact on trauma patients is unknown, however. OBJECTIVE: To assess
      the effect of CDAI on trauma patients and develop a scoring system to predict
      CDAI in that population. METHODS: Records of all trauma patients admitted to a
      Level I Trauma Center from 2001 to 2014 were retrospectively reviewed. Presence
      of CDAI was defined as evidence of positive toxin or polymerase chain reaction.
      Patients with CDAI were matched to patients without CDAI using propensity score
      matching on a ratio of 1:3. MAIN OUTCOME MEASURES: Primary outcome was inhospital
      mortality. Secondary outcomes included length of stay and need for mechanical
      ventilation. A decision-tree analysis was performed to develop a predicting model
      for CDAI in the study population. RESULTS: During the study period, 11,016
      patients were identified. Of these, 50 patients with CDAI were matched to 150
      patients without CDAI. There were no differences in admission characteristics and
      demographics. Patients in whom CDAI developed had significantly higher mortality
      (12% vs 4%, p < 0.01), need for mechanical ventilation (57% vs 23%, p < 0.01),
      and mean hospital length of stay (15.3 [standard deviation 1.4]) days vs 2.1
      [0.6] days, p < 0.0). CONCLUSION: In trauma patients, CDAI results in significant
      morbidity and mortality. The C difficile influencing factor score is a useful
      tool in identifying patients at increased risk of CDAI.

PMID- 30201091
TI  - Therapeutic Interferon Interchange in Relapsing Multiple Sclerosis Lowers Health
      Care and Pharmacy Expenditures with Comparable Safety.
AB  - INTRODUCTION: For patients with a less-active (fewer relapses or complete
      recovery from relapses, less radiologic burden of disease, or no or limited
      disease-related disability) relapsing form of multiple sclerosis (MS), interferon
      (IFN) beta-1b subcutaneous is similar in efficacy to IFN beta-1a intramuscular
      and subcutaneous. The purpose of this study was to assess the impact of patient
      interchange from an IFN beta-1a to IFN beta-1b. METHODS: This was a
      retrospective, pre-post study of adult patients with relapsing MS who underwent
      interchange from an IFN beta-1a to IFN beta-1b between April 15, 2014, and April
      30, 2015. Health care financial and utilization outcomes between the 6 months
      before and after interchange were compared, and safety outcomes after interchange
      were assessed. RESULTS: A total of 36 primarily white, middle-age, and female
      patients underwent interchange. Monthly total health care and pharmacy
      expenditures decreased by approximately 40% and 44%, respectively, from pre-to
      post interchange (p < 0.001). Health care utilization was unchanged (p < 0.05).
      Seven (43.8%) patients underwent interchange back to IFN beta-1a intramuscular.
      No patients underwent interchange back to IFN beta-1a subcutaneous. The most
      common adverse effect reported after interchange was injection-site reaction.
      CONCLUSION: Health care expenditures decreased and adverse effects were limited
      among patients with MS who underwent an interchange from an IFN beta-1a to IFN
      beta-1b. These findings suggest that a therapeutic interchange between IFNs for
      patients with less-active MS disease is well tolerated. Further research is
      needed to determine the impact of such an interchange on disease progression.

PMID- 30201092
TI  - Sex-dependent effects of in utero cannabinoid exposure on cortical function.
AB  - Cannabinoids can cross the placenta, thus may interfere with fetal
      endocannabinoid signaling during neurodevelopment, causing long-lasting deficits.
      Despite increasing reports of cannabis consumption during pregnancy, the
      protracted consequences of prenatal cannabinoid exposure (PCE) remain
      incompletely understood. Here, we report sex-specific differences in behavioral
      and neuronal deficits in the adult progeny of rat dams exposed to low doses of
      cannabinoids during gestation. In males, PCE reduced social interaction, ablated
      endocannabinoid long-term depression (LTD) and heightened excitability of
      prefrontal cortex pyramidal neurons, while females were spared. Group 1 mGluR and
      endocannabinoid signaling regulate emotional behavior and synaptic plasticity.
      Notably, sex-differences following PCE included levels of mGluR1/5 and TRPV1R
      mRNA. Finally, positive allosteric modulation of mGlu5 and enhancement of
      anandamide levels restored LTD and social interaction in PCE adult males.
      Together, these results highlight marked sexual differences in the effects of PCE
      and introduce strategies for reversing detrimental effects of PCE.

PMID- 30201093
TI  - The influence of the descending pain modulatory system on infant pain-related
      brain activity.
AB  - The descending pain modulatory system (DPMS) constitutes a network of widely
      distributed brain regions whose integrated function is essential for effective
      modulation of sensory input to the central nervous system and behavioural
      responses to pain. Animal studies demonstrate that young rodents have an immature
      DPMS, but comparable studies have not been conducted in human infants. In Goksan
      et al. (2015) we used functional MRI (fMRI) to show that pain-related brain
      activity in newborn infants is similar to that observed in adults. Here, we
      investigated whether the functional network connectivity strength across the
      infant DPMS influences the magnitude of this brain activity. FMRI scans were
      collected while mild mechanical noxious stimulation was applied to the infant's
      foot. Greater pre-stimulus functional network connectivity across the DPMS was
      significantly associated with lower noxious-evoked brain activity (p = 0.0004, r
      = -0.86, n = 13), suggesting that in newborn infants the DPMS may regulate the
      magnitude of noxious-evoked brain activity.

PMID- 30201095
TI  - Lamins Organize the Global Three-Dimensional Genome from the Nuclear Periphery.
AB  - Lamins are structural components of the nuclear lamina (NL) that regulate genome
      organization and gene expression, but the mechanism remains unclear. Using Hi-C,
      we show that lamins maintain proper interactions among the topologically
      associated chromatin domains (TADs) but not their overall architecture. Combining
      Hi-C with fluorescence in situ hybridization (FISH) and analyses of lamina
      associated domains (LADs), we reveal that lamin loss causes expansion or
      detachment of specific LADs in mouse ESCs. The detached LADs disrupt 3D
      interactions of both LADs and interior chromatin. 4C and epigenome analyses
      further demonstrate that lamins maintain the active and repressive chromatin
      domains among different TADs. By combining these studies with transcriptome
      analyses, we found a significant correlation between transcription changes and
      the interaction changes of active and inactive chromatin domains These findings
      provide a foundation to further study how the nuclear periphery impacts genome
      organization and transcription in development and NL-associated diseases.

PMID- 30201094
TI  - Biophysical properties of single rotavirus particles account for the functions of
      protein shells in a multilayered virus.
AB  - The functions performed by the concentric shells of multilayered dsRNA viruses
      require specific protein interactions that can be directly explored through their
      mechanical properties. We studied the stiffness, breaking force, critical strain
      and mechanical fatigue of individual Triple, Double and Single layered rotavirus
      (RV) particles. Our results, in combination with Finite Element simulations,
      demonstrate that the mechanics of the external layer provides the resistance
      needed to counteract the stringent conditions of extracellular media. Our
      experiments, in combination with electrostatic analyses, reveal a strong
      interaction between the two outer layers and how it is suppressed by the removal
      of calcium ions, a key step for transcription initiation. The intermediate layer
      presents weak hydrophobic interactions with the inner layer that allow the
      assembly and favor the conformational dynamics needed for transcription. Our work
      shows how the biophysical properties of the three shells are finely tuned to
      produce an infective RV virion.

PMID- 30201097
TI  - Recommendations for the Use of Etoposide-Based Therapy and Bone Marrow
      Transplantation for the Treatment of HLH: Consensus Statements by the HLH
      Steering Committee of the Histiocyte Society.
AB  - Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory
      syndrome requiring aggressive immunosuppressive therapy. Following 2 large
      international studies mainly targeting pediatric patients with familial disease
      and patients without underlying chronic or malignant disease, the HLH-94 protocol
      is recommended as the standard of care when using etoposide-based therapy by the
      Histiocyte Society. However, in clinical practice, etoposide-based therapy has
      been widely used beyond the study inclusion criteria, including older patients
      and patients with underlying diseases (secondary HLH). Many questions remain
      around these extended indications and published reports do not address several
      practical issues. To tackle these concerns, the HLH Steering Committee of the
      Histiocyte Society decided to issue guidance for use of the HLH-94 protocol. The
      group convened in a structured consensus finding process to define
      recommendations that are based largely on expert opinion backed up by available
      data from the literature. The recommendations address all main elements of HLH-94
      including corticosteroids, cyclosporin, etoposide, intrathecal therapy, and
      hematopoietic stem cell transplantation (HSCT) and consider various forms of HLH
      and all age groups. Aspects covered include indications, applications, dosing,
      side effects, duration of therapy, salvage therapy, and HSCT. These
      recommendations aim to provide a framework to guide treatment decisions in this
      severe disease.

PMID- 30201098
TI  - A case of chronic eosinophilic pneumonia successfully treated with mepolizumab.

PMID- 30201099
TI  - Corrigendum to "Chitosan-coated liposome dry-powder formulations loaded with
      ghrelin for nose-to-brain delivery" [Eur. J. Pharm. Biopharm. 129 (2018) 257
      266].

PMID- 30201101
TI  - Sex-related differences in the prevalence of cognitive impairment among
      overweight and obese adults with type 2 diabetes.
AB  - INTRODUCTION: Type 2 diabetes mellitus and obesity may increase risks for
      cognitive decline as individuals age. It is unknown whether this results in
      different prevalences of cognitive impairment for women and men. METHODS: The
      Action for Health in Diabetes, a randomized controlled clinical trial of a 10
      year intensive lifestyle intervention, adjudicated cases of cross-sectional
      cognitive impairment (mild cognitive impairment or dementia) 10-13 years after
      enrollment in 3802 individuals (61% women). RESULTS: The cross-sectional
      prevalences of cognitive impairment were 8.3% (women) and 14.8% (men): adjusted
      odds ratio 0.55, 95% confidence interval [0.43, 0.71], P < .001. Demographic,
      clinical, and lifestyle risk factors varied between women and men but did not
      account for this difference, which was limited to individuals without
      apolipoprotein E (APOE)-epsilon4 alleles (interaction P = .034). CONCLUSIONS:
      Among overweight and obese adults with type 2 diabetes mellitus, traditional risk
      factors did not account for the lower prevalence of cognitive impairment observed
      in women compared with men.

PMID- 30201100
TI  - Helicobacter pylori seropositivity and its association with incident all-cause
      and Alzheimer's disease dementia in large national surveys.
AB  - INTRODUCTION: Infectious agents were recently implicated in Alzheimer's disease
      (AD) and etiology of other dementias, notably Helicobacter pylori. METHODS: We
      tested associations of H. pylori seropositivity with incident all-cause and AD
      dementia and with AD-related mortality among US adults in a retrospective cohort
      study. Data from the National Health and Nutrition Surveys III, phase 1 (1988
      1991) and 1999-2000 linked with Medicare and National Death Index registries,
      were used (baseline age >=45 y, follow-up to 2013, Npooled = 5927). RESULTS: A
      positive association between H. pylori seropositivity and AD mortality was found
      in men (hazard ratioadj, pooled = 4.33, 95% confidence interval: 1.51-12.41, P =
      .006), which was replicated for incident AD and all-cause dementia, with hazard
      ratioadj, pooled = 1.45 (95% confidence interval: 1.03-2.04, P = .035) and hazard
      ratioadj, III = 1.44 (95% confidence interval: 1.05-1.98, P = .022),
      respectively. These associations were also positive among higher socioeconomic
      status groups. DISCUSSION: In sum, H. pylori seropositivity's direct association
      with AD mortality, all-cause dementia, and AD dementia was restricted to men and
      to higher socioeconomic status groups.

PMID- 30201096
TI  - Eosinophilic Esophagitis and the Eosinophilic Gastrointestinal Diseases: Approach
      to Diagnosis and Management.
AB  - The eosinophilic gastrointestinal diseases (EGIDs) represent disorders of the
      gastrointestinal (GI) tract that result from the local infiltration and aberrant
      activity of eosinophils and other immune cells. Eosinophilic esophagitis (EoE) is
      the most well-characterized EGID and is defined by the presence of
      intraepithelial eosinophils in the esophagus (>=15 eosinophils per high-powered
      field) and clinical symptoms associated with esophageal dysfunction. The other
      EGIDs are rare and lack strong data regarding pathogenesis and management. The
      incidence and prevalence of EoE are increasing, and EoE is now a major cause of
      upper GI morbidity. Management is multidisciplinary, with collaboration between
      gastroenterologists, allergists, pathologists, and dieticians, and is aimed at
      amelioration of symptoms and prevention of long-term complications such as
      esophageal stricture. Treatment options for EoE include proton pump inhibitors,
      swallowed topical corticosteroids, and elimination diets. Esophageal dilation is
      used when esophageal strictures or fibrostenotic changes are present. Additional
      therapies targeting eosinophils and other mediators of Th2 inflammation are under
      development and are promising. Treatment options for other EGIDs typically
      involve corticosteroids or dietary elimination.

PMID- 30201103
TI  - Comparative studies on the effects of high-fat diet, endurance training and
      obesity on Ucp1 expression in male C57BL/6 mice.
AB  - BACKGROUND: Obesity triggers a variety of severe conditions, therefore
      deteriorates metabolism rate of adipose tissues and muscles. Uncoupling proteins
      which are highly stimulated by fatty acids are potential targets for anti-obesity
      agents through breaking the electron gradient in the mitochondrial matrix and
      creating imbalances in the electron transport chain, thereby increasing the
      amount of substrate used to produce energy. Therefore, the aim of present study
      is assessment of exercise and high fat diet on expression level of Ucp1
      subcutaneous white and brown adipose tissues (scWAT & BAT) respectively. METHODS:
      To perform experiments, 48 male C57BL/6 mice were divided to two major groups and
      fed with high fat diet (HFD) or low fat diet (LFD) during a period of 12 weeks.
      After the first intervention, each groups was divided into four groups randomly
      as (HF-EX), (HF-SED), (LF-EX), (LF-SED) [EX: exercise; SED: sedentary] in form of
      treadmill running for 45 min/day, 5 days/week during 8 weeks. One day after the
      last practice session, mice were sacrificed and Ucp1 expression was assessed on
      scWAT & BAT. RESULTS: Data indicated a down-regulation in scWAT Ucp1 in obese
      mice similar to what observed for the expression of Pgc1alpha. Both, BAT Ucp1 and
      Pgc1alpha mRNA decreased significantly in response to obesity and physical
      activity. Moreover, exercise caused significant decrease in scWAT mitochondrial
      proteins contradictory to BAT. CONCLUSION: Taken together, exercise exerted
      controversial effects compared with HFD and obesity on expression of Ucp1 and
      Pgc1alpha in scWAT dissimilar to BAT tissues, concluding that obesity may cause a
      resistance to exercise in terms of metabolic demands for scWAT tissue.

PMID- 30201104
TI  - Identification and expression profiling of genes governing lignin biosynthesis in
      Casuarina equisetifolia L.
AB  - Casuarina equisetifolia L. is an important multi-purpose, fast growing and widely
      planted tree species native to tropical and subtropical coastlines of Australia,
      Southeast Asia, Malaysia, Melanesia, Polynesia and New Caledonia. It is a
      nitrogen-fixing tree mainly used for charcoal making, construction poles,
      landscaping, timber, pulp, firewood, windbreaks, shelterbelts, soil erosion and
      sand dune stabilization. Casuarina wood is presently used for paper and pulp
      production. Raw material with reduced lignin is highly preferred to increase the
      pulp yield. Hence, understanding the molecular regulation of wood formation in
      this tree species is vital for selecting industrially suitable phenotypes for
      breeding programs. The lignin biosynthetic pathway has been extensively studied
      in tree species like Eucalypts, poplars, pines, Picea, Betula and Acacia sp.
      However, studies on wood formation at molecular level is presently lacking in
      casuarinas. Hence, in the present study, the transcriptome of the developing
      secondary tissues of 15 years old Casuarina equiseitfolia subsp. equisetifolia
      was sequenced, de novo assembled, annotated and mapped to functional pathways.
      Transcriptome sequencing generated a total of 26,985 transcripts mapped to 31
      pathways. Mining of the annotated data identified nine genes involved in lignin
      biosynthesis pathway and relative expression of the transcripts in four tissues
      including scale-like leaves, needle-like brachlets, wood and root were
      documented. The expression of CeCCR1 and CeF5H were found to be significantly
      high in wood tissues, while maximum expression of CeHCT was documented in stem.
      Additionally, CeTUBA and CeH2A were identified as the most stable reference
      transcript for normalization of qRT-PCR data in C. equisetifolia. The present
      study is the first wood genomic resource in C. equisetifolia, which will be
      valuable for functional genomics research in this genus.

PMID- 30201105
TI  - Genetic association of AKR1B1 gene polymorphism rs759853 with diabetic
      retinopathy risk: A meta-analysis.
AB  - OBJECTIVE: The study aimed to ascertain the correlation between AKR1B1
      polymorphism rs759853 and the risk of diabetic retinopathy (DR) through a meta
      analysis. METHODS: Crude odds ratios (ORs) and the corresponding 95% confidence
      interval (95% CIs) were calculated to assess the association of AKR1B1 rs759853
      polymorphism with DR risk. Stratification analyses were further conducted based
      on ethnicity, diabetes mellitus (DM) type, Hardy-Weinberg equilibrium (HWE)
      status, and genotyping method. Heterogeneity was detected by Q test. Sensitivity
      analysis was implemented to check the robustness of final results. Additionally,
      Begg's funnel plot and Egger's test were used to evaluate underlying publication
      bias. RESULTS: Our meta-analysis ultimately incorporated 21 eligible publications
      with 22 independent case-control studies. The overall results demonstrated that
      AKR1B1 rs759853 polymorphism had no association with DR risk under all genetic
      models. However, after subgroup analysis by DM type, the rs759853 polymorphism
      was a protective factor against the DR onset in patients with type 1 DM (TT vs.
      CC: OR = 0.33, 95% CI = 0.17-0.67; TT + CT vs. CC: OR = 0.49, 95% CI = 0.36-0.68;
      TT vs. CC + CT: OR = 0.48, 95% CI = 0.28-0.83; allele T vs. allele C: OR = 0.56,
      95% CI = 0.44-0.72; CT vs. CC: OR = 0.52, 95% CI = 0.37-0.74). Furthermore,
      subgroup analysis by genotyping method suggested that rs759853 genotyped using
      MassARRAY assay was significantly correlated with decreased risk of DR under
      dominate model (TT + CT vs. CC: OR = 0.71, 95%CI = 0.52-0.96). CONCLUSION: AKR1B1
      polymorphism rs759853 may inhibit the occurrence of DR in patients with type 1
      DM.

PMID- 30201106
TI  - In-hospital Outcomes of Attempting More Than One Chronic Total Coronary Occlusion
      Through Percutaneous Intervention During the Same Procedure.
AB  - The frequency and outcomes of patients who underwent chronic total occlusion
      (CTO) percutaneous coronary intervention (PCI) of more than one CTO during the
      same procedure have received limited study. We compared the clinical and
      angiographic characteristics and procedural outcomes of patients who underwent
      treatment of single versus >1 CTOs during the same procedure in 20 centers from
      the United States, Europe, and Russia. A total of 2,955 patients were included:
      mean age was 65 +/- 10 years and 85% were men with high prevalence of previous
      myocardial infarction (46%), and previous coronary artery bypass graft surgery
      (33%). More than one CTO lesions were attempted during the same procedure in 58
      patients (2.0%) and 70% of them were located in different major epicardial
      arteries. Compared with patients who underwent PCI of a single CTO, those who
      underwent PCI of >1 CTOs during the same procedure had similar J-CTO (2.4 +/- 1.3
      vs 2.5 +/- 1.3, p = 0.579) and Prospective Global Registry for the Study of
      Chronic Total Occlusion Intervention (1.5 +/- 1.2 vs 1.3 +/- 1.0 p = 0.147)
      scores. The multi-CTO PCI group had similar technical success (86% vs 87%, p =
      0.633), but higher risk of in-hospital major complications (10.3% vs 2.7%, p =
      0.005), and consequently numerically lower procedural success (79% vs 85%, p =
      0.197). The multi-CTO PCI group had higher in-hospital mortality (5.2% vs 0.5%, p
      = 0.005) and stroke (5.2%vs 0.2%, p <0.001), longer procedure duration (162 [117
      to 242] vs 122 [80 to 186] minutes, p <0.001) and higher radiation dose (3.6 [2.1
      to 6.4] vs 2.9 [1.7 to 4.7] Gray, p = 0.033). In conclusion, staged
      revascularization may be the preferred approach in patients with >1 CTO lesions
      requiring revascularization, as treatment during a single procedure was
      associated with higher risk for periprocedural complications.

PMID- 30201102
TI  - Sex differences in functional and molecular neuroimaging biomarkers of
      Alzheimer's disease in cognitively normal older adults with subjective memory
      complaints.
AB  - INTRODUCTION: Observational multimodal neuroimaging studies indicate sex
      differences in Alzheimer's disease pathophysiological markers. METHODS: Positron
      emission tomography brain amyloid load, neurodegeneration (hippocampus and basal
      forebrain volumes adjusted to total intracranial volume, cortical thickness, and
      2-deoxy-2-[fluorine-18]fluoro-D-glucose-positron emission tomography metabolism),
      and brain resting-state functional connectivity were analyzed in 318 cognitively
      intact older adults from the INSIGHT-preAD cohort (female n = 201, male n = 117).
      A linear mixed-effects model was performed to investigate sex effects and
      sex*apolipoprotein E genotype interaction on each marker as well as sex*amyloid
      group interaction for non-amyloid markers. RESULTS: Men compared with women
      showed higher anterior cingulate cortex amyloid load (P = .009), glucose
      hypometabolism in the precuneus (P = .027), posterior cingulate (P < .001) and
      inferior parietal (P = .043) cortices, and lower resting-state functional
      connectivity in the default mode network (P = .024). No brain volumetric markers
      showed differences between men and women. Sex*apolipoprotein E genotype and
      sex*amyloid status interactions were not significant. DISCUSSION: Our findings
      suggest that cognitively intact older men compared with women have higher
      resilience to pathophysiological processes of Alzheimer's disease.

PMID- 30201107
TI  - Effect of Cigarette Smoking on Risk for Adverse Events in Patients With Heart
      Failure and Preserved Ejection Fraction.
AB  - Smoking is an important risk factor in the development of heart failure with
      preserved ejection (HFpEF), and previous reports have identified smoking as a
      significant predictor of death in this population. However, the relation between
      smoking and heart failure-specific outcomes has not been examined in patients
      with HFpEF. This analysis included 1,717 patients (mean age = 71 +/- 10 years;
      50% men; 78% white) with HFpEF enrolled in the Treatment of Preserved Cardiac
      Function Heart Failure with an Aldosterone Antagonist Trial from the Americas.
      Smoking was ascertained by self-reported history and categorized as never,
      former, or current. Multivariable Cox regression was used to examine the risk of
      hospitalization for heart failure, death, and cardiovascular death across smoking
      categories. There were 116 current smokers (7%), 871 former smokers (51%), and
      729 never smokers (42%) in this analysis. Current smoking was associated with an
      increased risk of hospitalization for heart failure (never: hazard ratio [HR]
      1.0; former: HR 1.25, 95% confidence interval [CI] 0.99 to 1.57; current: HR
      1.68, 95% CI 1.08 to 2.61), death (never: HR 1.0; former: HR 1.02, 95% CI 0.81 to
      1.29; current: HR 1.82, 95% CI 1.19 to 2.78), and cardiovascular death (never: HR
      1.0; former: HR 1.00, 95% CI 0.74 to 1.35; current: HR 1.85, 95% CI 1.09 to 3.24)
      compared with former or never smokers in a multivariable model adjusted for
      cardiovascular risk factors. A similar increased risk of hospitalization for
      heart failure (former: HR 1.0; current: HR 1.54, 95% CI 1.01, 2.36), death
      (former: HR 1.0; current: HR 1.81, 95% CI 1.19, 2.75), and cardiovascular death
      (former: HR 1.0; current: HR 1.76, 95% CI 1.04, 2.98) was observed for current
      smokers when we limited the analysis to those with a history of smoking. In
      conclusion, current smoking is associated with an increased risk for adverse
      outcomes in HFpEF, including hospitalization for heart failure. Smoking cessation
      strategies possibly have a role to reduce the risk for adverse cardiovascular
      outcomes in patients with HFpEF.

PMID- 30201109
TI  - Racial Comparisons of the Outcomes of Transcatheter and Surgical Aortic Valve
      Implantation Using the Medicare Database.
AB  - Racial disparities in the outcomes after intervention for aortic valve disease
      remain understudied. We stratified patients by race who underwent surgical aortic
      valve replacement (SAVR) and transcatheter aortic valve implantation (TAVI) in
      the Medicare database. The TAVI cohort consisted of 17,973 patients (3.9% were
      black and 1.0% were Hispanic). The SAVR cohort consisted of 95,078 patients,
      (4.8% were black and 1.3% were Hispanic). Most comorbidities were more common in
      blacks. After TAVI, 30-day mortality was not significantly different in races
      with both unadjusted and adjusted data. There were no significant racial
      differences in readmission rates or discharge to home after TAVI. After SAVR,
      black patients had worse unadjusted 30-day and 1-year mortality than whites or
      Hispanics (30-day mortality, 4.7% vs 6.2% vs 4.7% for whites, blacks, and
      Hispanics, respectively, p = 0.0001; 1-year mortality 11.7% vs 16.1% vs 12.5%,
      respectively, p = 0.0001); however, after adjustment, there were no differences
      in mortality. Black patients had higher 30-day readmission rates after SAVR
      (20.1% vs 25.2% vs 21.7% for whites, blacks, and Hispanics, respectively, p =
      0.0001), which persisted after adjustment for comorbidities. Minorities were
      underrepresented in both SAVR and TAVI relative to what would be predicted by
      population prevalence. In conclusion, while blacks have worse outcomes in SAVR
      compared with whites or Hispanics, race did not impact mortality, readmission, or
      discharge to home in TAVI. Both blacks and Hispanics were underrepresented
      compared with what would be predicted by population prevalence.

PMID- 30201108
TI  - Comparison of Effects of Statin Use on Mortality in Patients With Heart Failure
      and Preserved Versus Reduced Left Ventricular Ejection Fraction.
AB  - Randomized trials showed no survival benefit with statin therapy in heart failure
      (HF) patients with reduced ejection fraction (HFrEF). Whether these results are
      generalizable to HF patients with preserved ejection fraction (HFpEF) or with mid
      range ejection fraction is unclear. In a cohort of 13,440 patients with HF, 9,903
      (73.7%) were treated with statins. The association between statin use and all
      cause mortality was assessed with Cox proportional hazard regression models and
      survival time inverse probability weighting propensity scores analyses.
      Multivariable Poisson regression models with robust error variance were applied
      to estimate the rate ratios (RR) for hospitalization. The association between
      statin treatment and clinical outcomes differed by ejection fraction group. In
      patients with HFpEF, statin use was associated with reduced mortality (hazard
      ratio [HR] 0.73, 95% confidence interval [CI] 0.66 to 0.81, p <0.001; average
      treatment effect [ATE] 0.48, 95% CI 0.13 to 0.84, p = 0.007) and reduced all
      cause hospitalization (RR 0.82, 95% CI 0.76 to 0.89, p <0.001). In contrast, in
      patients with HFrEF, no significant association was observed between statin use
      and mortality (HR 0.86, 95% CI 0.74 to 1.0, p = 0.054; ATE 0.41, 95% CI -0.09 to
      0.93, p = 0.11) or hospitalization (RR 0.92, 95% CI 0.82 to 1.04, p = 0.17).
      Similarly, in patients with mid-range ejection fraction, there was no significant
      association with reduced mortality (HR 0.76, 95% CI 0.60 to 0.95, p = 0.02, ATE
      0.3, 95% CI -0.84 to 1.43, p = 0.61) or hospitalization (RR 1.07, 95% CI 0.9 to
      1.27, p = 0.44). In conclusion, statin use was associated with improved clinical
      outcomes in patients with HFpEF but not in patients with HFrEF or mid-range
      ejection fraction.

PMID- 30201110
TI  - Incidence, Predictive Factors, and Prognostic Impact of Silent Atrial
      Fibrillation After Transcatheter Aortic Valve Implantation.
AB  - New onset atrial fibrillation post-transcatheter aortic valve implantation (TAVI)
      is common and is associated with adverse outcomes. However, silent atrial
      fibrillation (AF) is poorly documented in the context. This study sought to
      evaluate the incidence, predictive factors, and prognostic value of Silent AF
      post-TAVI. All the consecutive patients with TAVI were prospectively analyzed by
      continuous electrocardiogram monitoring>=48 hours after implantation. Silent AF
      was defined as asymptomatic episodes lasting at least 30 seconds. The population
      was divided into 3 groups: history of AF, no-AF, and silent AF. Among the 206
      patients implanted with TAVI, 19 (16.1%) developed silent AF. Compared with the
      no-AF group, patients with silent AF shared the same clinical characteristics and
      cardiovascular risk factors. Procedural success and echography parameters after
      the device implantation were similar between groups. Left atrial volume was
      significantly increased (p <0.001) in the silent AF group, together with
      preimplantation C-reactive protein (CRP) >3 mg/L and glucose (p = 0.048 and p =
      0.002). By multivariate analysis, CRP >3 mg/dl and logistic European System for
      Cardiac Operative Risk Evaluation were identified as independent predictors of
      silent AF. In-hospital and 1-year mortalities were higher in pre-existing AF
      patients, whereas no-AF and the silent AF patients share the same prognosis. Our
      prospective study showed for the first time that silent AF is frequent after TAVI
      procedures. In conclusion, our work suggests that CRP could help to predict the
      risk of developing silent AF. However, the onset of silent AF is not associated
      with worse prognosis in the year following the procedure in our study.

PMID- 30201111
TI  - Prediction of Extensive Myocardial Fibrosis in Nonhigh Risk Patients With
      Hypertrophic Cardiomyopathy.
AB  - In nonhigh risk patients with hypertrophic cardiomyopathy (HC), the presence of
      extensive late gadolinium enhancement (LGEext) at cardiovascular magnetic
      resonance (CMR) imaging has been proposed as a risk modifier in the decision
      process for implantable cardioverter defibrillator implantation. With a pretest
      risk of about 10%, a strategy that alters the likelihood of LGEext could markedly
      affect efficacious CMR imaging. Our aim was to study the potential of clinical
      variables and biomarkers to predict LGEext. In 98 HC patients without any clear
      indication for implantable cardioverter defibrillator implantation, we determined
      the discriminative values of a set of clinical variables and a panel of
      biomarkers (hs-cTnT, NTproBNP, GDF-15, and Gal-3, CICP) for LGEext, that is, LGE
      >=15% of the left ventricular mass. LGEext was present in 10% (10/98) of
      patients. The clinical prediction model contained a history of nonsustained
      ventricular tachycardia, maximal wall thickness and reduced systolic function (c
      statistic: 0.868, p <0.001). Of all biomarkers, only hs-cTnT was associated with
      LGEext, in addition to the improved clinical model of diagnostic accuracy (p =
      0.04). A biomarker-only strategy allowed the exclusion of LGEext in half of the
      cohort, in case of a hs-cTnT concentration less than the optimal cutoff (Youden
      index; 8 ng/L-sensitivity 100%, specificity 54%). In conclusion, in this nonhigh
      risk HC cohort, the pretest likelihood of LGEext can be altered using clinical
      variables and the addition of hs-cTnT. The promising findings with the use of hs
      cTnT only call for new initiatives to study its impact on efficacious CMR imaging
      in a larger HC population, either with or without additional use of clinical
      variables.

PMID- 30201112
TI  - Transcatheter Versus Surgical Pulmonary Valve Replacement in Repaired Tetralogy
      of Fallot.
AB  - Transcatheter pulmonary valve replacement (TC-PVR) is an alternative to surgical
      PVR (S-PVR) in repaired Tetralogy of Fallot (TOF). The purpose of this study is
      to compare in-hospital outcomes, hospital costs, and projected 5-year total costs
      of S-PVR to TC-PVR in patients with repaired TOF. We performed a multicenter,
      retrospective cohort study of children and adults with TOF >= 8 years of age who
      underwent PVR from January 1, 2010 to December 31, 2016 at 46 centers
      contributing to the Pediatric Health Information Systems database. Baseline
      characteristics, in-hospital outcomes, and costs were compared between the two
      groups. Projected 5-year costs were calculated by combining cost data with
      published reintervention rates. A total of 194 TC-PVR and 1,072 S-PVR were
      performed. The baseline characteristics of the TC-PVR and S-PVR groups were not
      significantly different with the exception of greater age in the TC-PVR group
      (median age of 17 years vs 15 years, p value <0.001). Discharge mortality,
      hospital charges and estimated cost, surgical complication rates, and acute
      kidney failure were not significantly different between the groups. Intensive
      care unit use, intensive care unit length of stay (LOS), mechanical ventilation
      use, extracorporeal membrane oxygenation use, and total LOS were lower with TC
      PVR than S-PVR. Projected 5-year costs were greater with TC-PVR compared with S
      PVR ($64,762 vs $56,536) due to the cost of the transcatheter pulmonary valve and
      higher reintervention rates. In conclusion, despite longer LOS and greater in
      hospital resource utilization for patients with TOF who underwent S-PVR compared
      with TC-PVR, mortality, and in-hospital costs are the same, and projected 5-year
      costs are less.

PMID- 30201113
TI  - Effect of Patent Foramen Ovale in Patients With Pulmonary Hypertension.
AB  - Septostomy reduces right ventricular (RV) workload at the expense of hypoxemia in
      patients with advanced pulmonary hypertension (PH). A patent foramen ovale (PFO)
      may serve as a "natural" septostomy, but the incidence and impact of a PFO in PH
      remains uncertain. We prospectively examined echocardiograms in 404 PH patients
      referred for initial hemodynamic assessment. Patients included had saline bubble
      injection and if negative repeatinjection after Valsalva maneuver.
      Echocardiographic and hemodynamic data were examined. Survival was modeled using
      Kaplan-Meier method. Eisenmenger syndrome or known atrial shunts other than PFO
      were excluded: 292 patients met entry criteria. A PFO was identified in 16.8% of
      the entire cohort, 22.9% of pulmonary arterial hypertension (PAH) patients, and
      8.6% of Dana Point group 2 PH patients. Right atrial to pulmonary capillary wedge
      pressure difference was lowest in the latter group (-7.9 +/- 7.1 vs -1.7 +/- 5.5
      mm Hg for all others, p <0.01). Patients with a PFO were younger (53.9 vs 58.6
      years, p = 0.02). A PFO was more often present with moderately or severely
      dilated (p = 0.01) or dysfunctional (p = 0.03) RVs. Six year survival was
      unchanged by PFO presence for all patients, including those with PAH.
      Proportional hazards analysis found only age and functional class independently
      predicted survival (p <0.01). A PFO is identified less often in Dana Point group
      2 PH, likely due to inability of Valsalva maneuver to overcome right atrial to
      pulmonary capillary wedge pressure difference. In conclusion, the incidence of a
      PFO in the PH population increases with more dilated and dysfunctional RVs,
      suggesting that the PFO may be stretched open rather than congenital. The
      presence of a PFO does not impact survival in PH or PAH.

PMID- 30201114
TI  - Clinical and Hemodynamic Results After Conversion from Single to Biventricular
      Circulation After Fetal Aortic Stenosis Intervention.
AB  - At our institution a multidisciplinary team has performed fetal aortic
      valvuloplasty (FAV) for severe aortic stenosis with evolving hypoplastic left
      heart syndrome with high technical success rates. Measurement of postnatal
      success has been biventricular circulation (BC). Postnatal survival for patients
      after FAV who achieved a BC appears encouraging. However, there are limited late
      clinical and hemodynamic outcomes in this cohort and there is concern for
      diastolic dysfunction. We reviewed all patients with FAV at our institution who
      initially underwent single ventricle palliation and subsequently BC, as this is
      likely the subset at high-risk for poor outcomes. Clinical, imaging, and surgical
      data were collected. Two of 7 patients (29%) died within 16 months of BC, and 1
      patient has been listed for transplant. Diastolic dysfunction was common and
      progressive with median left ventricular end diastolic pressure of 12 mm Hg
      before BC, and increasing to 22 mm Hg for survivors at last follow-up. Left
      ventricular size was adequate with all patients reaching a left ventricular end
      diastolic volume (LVEDV) z score in the normal or elevated range. Presence and
      severity of residual valve lesions decreased over time secondary to a median of 6
      interventions (range 3 to 10), either surgical or cath-based, performed for these
      7 patients during the study period. In conclusion, clinical outcomes are
      concerning for this high-risk group. Diastolic dysfunction is persistent and
      progressive despite anatomic interventions and adequate left ventricular growth.
      The main contributing factor to poor outcomes may be intrinsic myocardial
      dysfunction and primordial pathology. Achievement of a BC after FAV may not be an
      appropriate measure of success.

PMID- 30201116
TI  - A systematic review and meta-analysis of CBT interventions based on the Fennell
      model of low self-esteem.
AB  - Low self-esteem is a feature of several mental health disorders that has been
      directly treated with Cognitive-Behavioral Therapy (CBT). The aim of our study
      was to determine the efficacy of interventions for improving low self-esteem in
      adults by utilizing the model outlined in Fennell (1997; 1998; 1999). A
      literature search identified 8 studies that met the inclusion criteria of CBT
      based interventions for low self-esteem using this model, 7 of which were used in
      a quantitative synthesis. These studies included weekly group and individual
      sessions and one-day workshop formats. Summary effect sizes of 1.12 and 0.34 at
      post-treatment were observed, with low levels of heterogeneity, for weekly
      sessions and one-day workshops, respectively. Comparable results were found for
      the reduction of depressive symptoms. Results suggest that CBT-based
      interventions may be efficacious for treating individuals with low self-esteem,
      according to changes in self-report measures; however, it is unclear whether
      these interventions are dissimilar to those aimed at reducing depression.

PMID- 30201117
TI  - Lack of correlation of ECV and outcome in an in vivo murine model of systemic
      fusariosis.
AB  - The efficacy of liposomal amphotericin B and voriconazole was evaluated against
      the systemic infection by Fusarium oxysporum species complex or Fusarium
      keratoplasticum. Although MIC values were within the epidemiological cutoff
      values (ECVs) recently stablished for Fusarium spp., no efficacy was obtained,
      indicating that ECVs for Fusarium are not relevant for in vivo efficacy.

PMID- 30201118
TI  - Prognostic Significance and Risk of Atrial Fibrillation of Wolff-Parkinson-White
      Syndrome in Patients With Hypertrophic Cardiomyopathy.
AB  - To assess the mid-term mortality and risk of atrial fibrillation (AF) in patients
      with hypertrophic cardiomyopathy (HC) and Wolff-Parkinson-White (WPW) syndrome,
      40 patients with HC and WPW were enrolled in our center between 2010 and 2017. An
      age- and gender-matched comparison cohort of patients with HC without WPW (n =
      160) was generated from the same center. The clinical profile and outcomes were
      assessed. Of 40 patients with WPW, 28 underwent accessory pathway (AP)
      elimination. Two patients (7%) had failed in AP elimination. During mid-term
      follow-up, 1 patient had an implantable cardioverter-defibrillator intervention.
      Fourteen patients had AF. A previous history of AF (hazard ratio [HR]: 4.69; 95%
      confidence interval [CI] 1.51 to 14.63) and left atrial dimension (HR: 1.12; 95%
      CI 1.03 to 1.23) at baseline were risk factors for AF occurrence during follow
      up. The AP elimination significantly reduced risk for the incidence of AF (HR:
      0.22; 95% CI 0.06 to 0.83). Compared with the control group, the prevalence of
      syncope and AF were significantly higher in the WPW group. During follow-up, no
      difference was identified in outcome measures consisting of all-cause death,
      cardiac transplantation, and implantable cardioverter-defibrillator intervention.
      A previous history of AF (HR: 5.20; 95% CI 2.63 to 10.30, p <0.001) and
      persistent existing WPW (HR: 3.64; 95% CI 1.63 to 8.11, p = 0.002) were
      independent risk factors for AF occurrence during follow-up in the entire cohort.
      In conclusion, although WPW was uncommon and might not be correlated with mid
      term mortality in HC patients, WPW might increase the risk of AF occurrence.
      Additionally, AP elimination may reduce the risk of AF occurrence.

PMID- 30201119
TI  - The bony labyrinth in the Aroeira 3 Middle Pleistocene cranium.
AB  - The discovery of a partial cranium at the site of Aroeira (Portugal) dating to
      389-436 ka augments the current sample of Middle Pleistocene European crania and
      makes this specimen penecontemporaneous with the fossils from the geographically
      close Atapuerca Sima de los Huesos (SH) and Arago sites. A recent study of the
      cranium documented a unique combination of primitive and derived features. The
      Aroeira 3 cranium preserves the right temporal bone, including the petrosal
      portion. Virtual reconstruction of the bony labyrinth from MUCT scans provides an
      opportunity to examine its morphology. A series of standard linear and angular
      measures of the semicircular canals and cochlea in Aroeira 3 were compared with
      other fossil hominins and recent humans. Our analysis has revealed the absence of
      derived Neandertal features in Aroeira 3. In particular, the specimen lacks both
      the derived canal proportions and the low position of the posterior canal, two of
      the most diagnostic features of the Neandertal bony labyrinth, and Aroeira 3 is
      more primitive in these features than the Atapuerca (SH) sample. One potentially
      derived feature (low shape index of the cochlear basal turn) is shared between
      Aroeira 3 and the Atapuerca (SH) hominins, but is absent in Neandertals. The
      results of our study provide new insights into Middle Pleistocene population
      dynamics close to the origin of the Neandertal clade. In particular, the
      contrasting inner ear morphology between Aroeira 3 and the Atapuerca (SH)
      hominins suggests a degree of demographic isolation, despite the close geographic
      proximity and similar age of these two sites.

PMID- 30201121
TI  - Perfection is the enemy of good: Pushing the boundaries of donor heart criteria.

PMID- 30201120
TI  - Saliva oxytocin, cortisol, and testosterone levels in adolescent boys with autism
      spectrum disorder, oppositional defiant disorder/conduct disorder and typically
      developing individuals.
AB  - The aim of the current study was to compare levels of oxytocin, cortisol, and
      testosterone in adolescents with either autism spectrum disorder (ASD), or
      oppositional defiant disorder (ODD)/conduct disorder (CD), and in typically
      developing individuals (TDI), and relate hormone levels to severity and subtype
      of aggression and callous-unemotional (CU) traits. Saliva concentrations of
      oxytocin, cortisol, and testosterone were assessed in 114 male participants (N =
      49 ASD, N = 37 ODD/CD, N = 28 TDI,) aged 12-19 years (M = 15.4 years, SD = 1.9).
      The ASD and the ODD/CD groups had significantly lower levels of oxytocin than the
      TDI group, and the ODD/CD group had significantly higher levels of testosterone
      than the ASD group. There were no group effects on cortisol levels. Group
      differences remained for oxytocin after correcting for the influence of CU
      traits, but were not significant after controlling for aggression. Results for
      testosterone became non-significant after correction for either CU traits or
      aggression. Across groups, higher levels of CU traits were related to higher
      levels of cortisol and testosterone, however, proactive and reactive aggression
      were unrelated to all three hormonal levels. The current findings show that,
      regardless of cognitive ability or comorbid disorders, the diagnostic groups
      (ASD, ODD/CD) differ from each other by their hormonal levels, with the ASD group
      characterized by relative low level of oxytocin, and the ODD/CD group by a
      relative low level of oxytocin and high level of testosterone. These group
      effects were partly driven by differences in CU traits between the groups.

PMID- 30201122
TI  - Should a surgeon comply with hospital administration's demand to change valve
      preference?

PMID- 30201123
TI  - John Lockwood Ochsner: Celebration of life.

PMID- 30201124
TI  - Early left ventricular assist device-related strokes: Turn up the flow, turn down
      the embolism?

PMID- 30201125
TI  - Fate of uncomplicated acute type B aortic dissection and impact of concurrent
      aortic dilatation on remote aortic events.
AB  - OBJECTIVE: This study aimed to describe the reliable prognostic factors of
      mortality and subsequent aortic events during the follow-up of uncomplicated type
      B acute aortic dissection. METHODS: From January 2004 to December 2014, 255
      patients with uncomplicated type B acute aortic dissection were admitted to our
      hospital. Cox proportional hazards analysis was performed to identify risk
      factors for all-cause mortality, aorta-related mortality, and aortic events.
      RESULTS: In-hospital mortality was observed in 7 patients (2.7%). The rates of 5
      year freedom from all-cause mortality, aorta-related mortality, and aortic events
      were 79.4% +/- 2.9%, 93.3% +/- 2.0%, and 71.7% +/- 3.4%, respectively. The rate
      of 5-year freedom from aortic events was significantly lower among those with a
      patent false lumen (P = .006). Age and descending aorta diameter were independent
      risk factors of all-cause and aorta-related mortality (hazard ratio [HR], 1.08
      and 1.13; 95% confidence interval [CI], 1.04-1.10 and 1.03-1.24; P = .0001 and
      .007, respectively). Independent risk factors for aortic events were descending
      aorta diameter, false lumen thickness, and dilatation of abdominal aorta (HR,
      1.06; 95% CI, 1.02-1.12; P = .006; HR, 1.07; 95% CI, 1.04-1.11; P = .00002; HR,
      2.01; CI, 1.20-3.38; P = .008). CONCLUSIONS: In uncomplicated type B acute aortic
      dissection, the age and dilatation of the thoracic aorta were associated with a
      higher risk of death, whereas false lumen thickness and concurrent abdominal
      aortic dilatation augment the risk for aortic events.

PMID- 30201126
TI  - Expanding left ventricular assist device use to patients with disabilities: The
      role of assistive technology.

PMID- 30201127
TI  - Intraoperative complication rates in cataract surgery performed by ophthalmology
      resident trainees compared to staff surgeons in a Canadian academic center.
AB  - PURPOSE: To compare the intraoperative complication rates in cataract surgery
      performed by resident trainees and staff ophthalmologists. SETTING: Kensington
      Eye Institute, University of Toronto, Toronto, Canada. DESIGN: Prospective case
      series. METHODS: This study included 8738 consecutive cases of primary
      phacoemulsification cataract surgery performed by staff surgeons and resident
      trainees from January to December 2016. There were no exclusion criteria. Data
      collected included the level of resident training, case complexity, degree of
      resident involvement, and intraoperative complications. Primary outcome measures
      included intraoperative complication rates and level of complexity of cataract
      surgeries performed by resident trainees and staff surgeons. RESULTS: Resident
      trainees were involved in 44% of surgeries. Of those, 82% were completed in their
      entirety by a resident and 18% were performed by both the staff surgeon and
      resident. Staff surgeons performed 56% of all surgeries without resident
      involvement. Sixty-seven percent of surgeries were simple and 33% were complex,
      with small pupil or intraoperative floppy-iris syndrome being the most common
      reason for complex cases. For simple cases, there was no difference in the
      overall complication rates (1.7% and 2.0%; P = .52), posterior capsule rupture
      rates (0.9% and 0.8%; P = .76), or vitreous loss rates (0.4% and 0.2%; P = .08)
      between staff and residents, respectively. CONCLUSION: There were no differences
      in complication rates between the two groups.

PMID- 30201128
TI  - Astigmatic outcomes in myopic wavefront-guided laser in situ keratomileusis
      versus wavefront-guided photorefractive keratectomy using vector analysis.
AB  - PURPOSE: To compare astigmatic outcomes between eyes having wavefront-guided
      laser in situ keratomileusis (LASIK) and eyes having wavefront-guided
      photorefractive keratectomy (PRK). SETTING: Byers Eye Institute, Stanford
      University School of Medicine, Palo Alto, California, USA. DESIGN: Prospective
      randomized case series. METHODS: Patients had refractive surgery, with one eye
      treated with LASIK and the other treated with PRK. Eyes were randomized according
      to ocular dominance. Astigmatism vectors were evaluated using the Alpins vector
      analysis of astigmatism. RESULTS: Thirty-four patients (68 eyes) had vector
      analysis; the LASIK and PRK groups had similar target-induced astigmatism vectors
      (P = 0.75), surgically induced astigmatism vectors (P = 0.86), difference vectors
      (P = 1.0), indices of success (P = 0.4), correction indices (P = 0.28), and
      flattening indices (P = 0.5). CONCLUSION: Based on Alpins vector analysis of
      astigmatism, there were no statistically significant differences between eyes
      that had LASIK and eyes that had PRK.

PMID- 30201129
TI  - Intraoperative performance and ultrastructural integrity of human capsulotomies
      created by the improved precision pulse capsulotomy device.
AB  - PURPOSE: To investigate the intraoperative performance and the ultrastructural
      features of anterior capsulotomy performed with the improved Zepto precision
      pulse capsulotomy (PPC) device. SETTING: Launceston Eye Institute, Launceston,
      Tasmania, Australia. DESIGN: Prospective, consecutive case series. METHODS:
      Intraoperative observation of performance and complications were made on
      consecutive eyes having capsulotomies with the improved PPC device. The
      capsulotomy specimens were examined under scanning electron microscope and
      compared with manual continuous curvilinear capsulorhexis and femtosecond laser
      assisted cataract surgery specimens. RESULTS: The study comprised 52 eyes.
      Intended capsulotomy occurred in 50 eyes with 2 device failures. Complete free
      floating capsulotomies were achieved in 48 eyes (96%). Anterior capsule tears
      occurred in 2 eyes (4%). CONCLUSIONS: The ability of the PPC device to create
      complete free-floating capsulotomies improved; however, the radial tear rate
      remained high. The ultrastructural features in ex vivo human capsulotomy
      specimens still showed areas of irregular capsule margin with frayed edges.

PMID- 30201130
TI  - Effect of high vacuum and aspiration on phacoemulsification efficiency and
      chatter using a transversal ultrasound machine.
AB  - PURPOSE: To examine the role of high vacuum and aspiration settings on efficiency
      using a transversal ultrasound (US) machine. SETTING: John A. Moran Eye Center
      Laboratory, University of Utah, Salt Lake City, Utah, USA. DESIGN: Experimental
      study. METHODS: Porcine lens nuclei were incubated in formalin for 2 hours and
      then cut into 2.0 mm cubes. Phacoemulsification was performed using the Whitestar
      Signature machine. Settings were bottle height 50 cm, on-time 6 milliseconds, and
      off-time 6 milliseconds. One hundred percent power was used for all 240 runs.
      Tested parameters were aspiration of 50 mL/min and 60 mL/min and vacuum of 500,
      mm Hg, 600 mm Hg, and 650 mm Hg. RESULTS: With continuous US, increasing
      aspiration from 50 mL/min to 60 mL/min significantly increased efficiency (23%).
      Increasing vacuum from 500 mm Hg to 650 mm Hg and from 600 mm Hg to 650 mm Hg
      significantly increased efficiency (20.2% and 13.6%, respectively). Higher vacuum
      and aspiration parameters did not influence the incidence of chatter events. In
      the micropulse US group, there was no significant efficiency increase with
      increasing vacuum or aspiration levels. There was a significant efficiency
      increase of continuous over micropulse US at an aspiration setting of 60 mL/min
      and vacuum settings of 600 mm Hg and 650 mm Hg. CONCLUSIONS: As aspiration and
      vacuum increased, efficiency increased under continuous transverse US. No
      significant efficiency improvement occurred at high aspiration and vacuum
      settings under micropulse US. At 60 mL/min aspiration and more than 600 mm Hg
      vacuum, continuous power was significantly more efficient than micropulse
      transverse US.

PMID- 30201131
TI  - Molecular epidemiology and clinical features of rhinovirus infections among
      hospitalized patients in a medical center in Taiwan.
AB  - BACKGROUND: Human rhinovirus (HRV) can cause severe illnesses in hospitalized
      patients. However, there are no studies regarding the prevalence of HRV
      infection, particularly the recently identified HRV-C, in hospitalized patients
      reported from Taiwan. METHODS: Respiratory specimens collected from 487
      hospitalized patients in designated wards between 2013 and 2014 in a medical
      center in northern Taiwan were retrospectively detected for HRV. Positive
      specimens were further determined for genotyping. Medical charts of the HRV
      positive patients were reviewed retrospectively. RESULTS: Totally, 76 patients
      (15.6%) were HRV positive, of which 60 were pediatric patients. HRV-A was
      identified in 41 (54%) patients, HRV-B in 6 patients (7.9%) and HRV-C in 29
      patients (38%). A total of 47 different genotypes were identified. HRV infections
      were predominant during fall and winter seasons. 21.1% were affected by HRV alone
      and 78.9% were found to be co-infected with other microorganisms. The detection
      rate of HRV in children (18.6%) was significantly higher than in adults (9.6%).
      Compared with pediatric patients, adult patients were significantly associated
      with underlying disease, Pneumocystis jirovesii pneumonia co-infection, a
      diagnosis of pneumonia, fatal outcome, hospital acquisition of HRV, antibiotics
      administration and requiring intensive care, while pediatric patients were
      significantly associated with viral co-infection. CONCLUSIONS: HRV was a common
      cause of respiratory tract infection in Taiwan, particularly in pediatric
      patients. Eighty percent of HRV-infected inpatients had other microorganisms co
      infection. Adult patients were more likely to be associated with a severe
      respiratory disease entity.

PMID- 30201132
TI  - Vancomycin-resistant Enterococcus faecium at a university hospital in Taiwan,
      2002-2015: Fluctuation of genetic populations and emergence of a new structure
      type of the Tn1546-like element.
AB  - BACKGROUND/PURPOSES: Vancomycin resistance increased significantly to 31.3% among
      Enterococcus faecium in 2006 and remained high thereafter at a university
      hospital in Taiwan. A longitudinal study was retrospectively conducted to
      characterize these vancomycin-resistant E. faecium (VRE-fm). METHODS: A total of
      378 non-repetitive VRE-fm blood isolates collected during 2002-2015 were studied.
      Multilocus sequence typing, pulsed-field gel electrophoresis, analysis of van
      genes and the Tn1546 structure, and conjugation experiments were performed.
      RESULTS: The majority (78.0%) of the isolates were associated with hospital
      acquired infections. Molecular typing revealed nine major pulsotypes and five
      predominant sequence types (STs): ST17 (33.9%), ST78 (18.3%), ST414 (14.6%), ST18
      (10.6%), and ST203 (7.4%). Fluctuation of these prevailing STs among the study
      years in association with some major pulsotypes was noted. All isolates carried
      vanA genes, except that in four isolates vanB genes were found. Among the vanA
      carrying Tn1546-like elements, one predominant structure type (Type I, 55.9%) was
      noted throughout the study years. Since 2009, another predominant structure type
      (Type II, 40.1%) has emerged firstly in ST414 and gradually spread to other 11
      STs in subsequent years. Isolates carrying these Type II Tn1546-like elements
      have become the most predominant population since 2014, majorly found in ST78 and
      ST17. Preliminary experiments indicated that plasmids carrying the Type II Tn1546
      like elements demonstrated ten-fold higher efficiency than those carrying the
      Type I Tn1546-like elements. CONCLUSION: Dissemination of some major STs and
      horizontal transfer of plasmids carrying two major structure types of Tn1546-like
      elements may have together contributed to the increase of VRE-fm infection.

PMID- 30201134
TI  - One fungus, several microbes.

PMID- 30201133
TI  - Molecular epidemiology of the emerging ceftriaxone resistant non-typhoidal
      Salmonella in southern Taiwan.
AB  - BACKGROUND/PURPOSE: The increasing trend of ceftriaxone resistant non-typhoidal
      Salmonella (NTS) worldwide is of serious concern, however, data is lacked in
      southern Taiwan. METHODS: Salmonella isolates were collected at a regional
      hospital in Kaohsiung during 2004-2013. Ceftriaxone resistant NTS isolates were
      further characterized for beta-lactamases, typed by pulsed field gel
      electrophoresis (PFGE), multilocus sequence typing (MLST) and their plasmids were
      analyzed by PCR replicon typing and plasmid mutilocus sequence typing. RESULTS:
      Among 528 NTS isolates, the most common serogroup is serogroup B (44.9%),
      followed by serogroup D, and serogroup C. Eleven (2.1%) isolates were resistant
      to ceftriaxone and were distributed in three peak periods (2010, 2011, and 2013).
      PFGE and MLST revealed the ten serogroup B isolates were of two clones. Beta
      lactamase genes were detected in 10 of the 11 isolates, including CMY-2 (5
      isolates), TEM-1 (2), CTX-M-14 (1), and 2 isolates carried both TEM-1 and CMY-2.
      Plasmid incompatibility types were identified in 9 (81.8%) isolates; three were
      IncI1, three was IncHI2, one was IncFIB and two had both replicons of IncI1 and
      IncHI2. The only ESBL gene blaCTM-X-14 was found in an isolate with plasmid
      belonged to IncHI2, which has not been reported in NTS in Taiwan before. Most
      MLST types and plasmid MLST types of NTS isolates in this study are different
      from those in northern Taiwan. CONCLUSION: Though clonal spread of ceftriaxone
      resistant NTS was suggested by PFGE and MLST, plasmid characterization and beta
      lactamase detection revealed their plasmid types and beta-lactamase types were
      different.

PMID- 30201135
TI  - Bronchopulmonary dysplasia: Pathophysiology and potential anti-inflammatory
      therapies.
AB  - Inflammation of the preterm lungs is key to the pathogenesis of bronchopulmonary
      dysplasia (BPD), whether it arises as a consequence of intrauterine inflammation
      or postnatal respiratory management. This review explores steroidal and non
      steroidal therapies for reducing neonatal pulmonary inflammation, aimed at
      treating or preventing BPD.

PMID- 30201137
TI  - Engage specialists to achieve value in healthcare: An interview with Brookings
      Institution Fellow Kavita Patel.

PMID- 30201138
TI  - Effectiveness of computed tomography scanning to detect blunt bowel and
      mesenteric injuries requiring surgical intervention: A systematic literature
      review.
AB  - BACKGROUND: Computed tomography (CT) diagnostic accuracy for blunt bowel and
      mesenteric injuries (BBMI) is controversial. DATA SOURCES: A literature review to
      compute aggregate CT performance and individual CT sign sensitivity, specificity,
      and positive predictive value (PPV) for operative BBMI. CONCLUSIONS: Sensitivity,
      specificity, and PPV were: overall CT performance 85.3%, 96.1%, 51.4%; abnormal
      wall enhancement 30.1%, 95.7%, 64.0%; bowel wall discontinuity 22.3%, 99.0%,
      87.9%; bowel wall hematoma 22.5%, 100%, 19.5%; bowel wall thickening 35.2%,
      96.5%, 32.1%; free air 32.0%, 98.7%, 57.1%; free fluid 65.6%, 85.0%, 25.5%;
      mesenteric air 27.6%, 99.1%, 85.3%; mesenteric extravasation 22.9%, 99.6%, 73.9%;
      mesenteric hematoma/fluid 33.9%, 98.7%, 52.8%; mesenteric stranding/streaking
      34.3%, 91.8%, 31.6%; mesenteric vessel beading 32.1%, 97.2%, 60.4%; mesenteric
      vessel termination 31.6%, 97.2%, 63.5%; oral contrast extravasation 10.0%, 100%,
      100%; retroperitoneal air 9.4%, 94.9%, 55.6%; and retroperitoneal fluid 44.2%,
      49.4%, 38.5%. Sensitivity, specificity, and PPV vary substantially among known
      signs. Other clinical factors are necessary for comprehensive BBMI
      identification.

PMID- 30201136
TI  - Development of a Gateway-compatible pCAMBIA binary vector for RNAi-mediated gene
      knockdown in plants.
AB  - RNA interference (RNAi), based on hairpin RNA (hpRNA) expression, plays an
      important role in functional analysis of plant genes. Traditional methods for
      making RNAi constructs usually involve multiple time-consuming cloning steps. We
      have developed a Gateway-compatible binary vector for RNAi-mediated gene
      knockdown in plants from pCAMBIA2301 and pHANNIBAL vectors. The new plant RNAi
      binary vector, named pCAMBIA2301-GW-RNAi, has two inverted repeated Gateway
      cassettes driven by the cauliflower mosaic virus 35S (CaMV 35S) promoter. This
      enables site-specific recombination at two sites by one Gateway LR reaction
      without restriction enzymes and ligases. The pCAMBIA2301-GW-RNAi vector's
      effectiveness was evaluated by Agrobacterium-mediated transient co-expression
      assays of overexpression and silencing constructs of HvCEBiP in Nicotiana
      benthamiana followed by western blot analysis. Obtained results show that the
      developed RNAi vector successfully knocked down 35S-driven expression of HvCEBiP,
      as expression levels of the encoded HvCEBiP protein were significantly reduced.

PMID- 30201139
TI  - Predictors of adequate lymph node harvest during colectomy for colon cancer.
AB  - BACKGROUND: Consensus guidelines recommend a yield of 12 lymph nodes in
      resections for colon cancer. Factors affecting this yield are not well defined.
      METHODS: Retrospective study using the colectomy-targeted American College of
      Surgeons National Surgical Quality Improvement Program for years 2014-2016.
      Primary outcome was resection of at least 12 nodes. Univariate and multivariate
      analyses determined factors associated with >=12 LN yield. RESULTS: 17,612
      colectomies for colon cancer were extracted from the NSQIP database. 7.26% of
      cases did not reach a 12 LN harvest. Harvesting >=12 LN was 74% more likely (p =
      0.001) if the resection was laparoscopic and 72% more likely (p < 0.0001) if hand
      assisted. Advanced T and N stage had a higher likelihood of reaching 12 LN
      harvest. Older age, female gender and smoking history decreased the likelihood of
      >=12 LN harvest. CONCLUSIONS: Laparoscopic and robotic colectomies were 1.5-2.5
      times more likely to achieve adequate LN harvest compared to open surgery.
      Several non-modifiable patient and disease related factors may render adequate LN
      yield challenging.

PMID- 30201140
TI  - Adamts10 inactivation in mice leads to persistence of ocular microfibrils
      subsequent to reduced fibrillin-2 cleavage.
AB  - Mutations in the secreted metalloproteinase ADAMTS10 cause recessive Weill
      Marchesani syndrome (WMS), comprising ectopia lentis, short stature,
      brachydactyly, thick skin and cardiac valve anomalies. Dominant WMS caused by
      FBN1 mutations is clinically similar and affects fibrillin-1 microfibrils, which
      are a major component of the ocular zonule. ADAMTS10 was previously shown to
      enhance fibrillin-1 assembly in vitro. Here, Adamts10 null mice were analyzed to
      determine the impact of ADAMTS10 deficiency on fibrillin microfibrils in vivo. An
      intragenic lacZ reporter identified widespread Adamts10 expression in the eye,
      musculoskeletal tissues, vasculature, skin and lung. Adamts10-/- mice had reduced
      viability on the C57BL/6 background, and although surviving mice were slightly
      smaller and had stiff skin, they lacked brachydactyly and cardiovascular defects.
      Ectopia lentis was not observed in Adamts10-/- mice, similar to Fbn1-/- mice,
      most likely because the mouse zonule contains fibrillin-2 in addition to
      fibrillin-1. Unexpectedly, in contrast to wild-type eyes, Adamts10-/- zonule
      fibers were thicker and immunostained strongly with fibrillin-2 antibodies into
      adulthood, whereas fibrillin-1 staining was reduced. Furthermore, fibrillin-2
      staining of hyaloid vasculature remnants persisted post-natally in Adamts10-/-
      eyes. ADAMTS10 was found to cleave fibrillin-2, providing an explanation for
      persistence of fibrillin-2 at these sites. Thus, analysis of Adamts10-/- mice led
      to identification of fibrillin-2 as a novel ADAMTS10 substrate and defined a
      proteolytic mechanism for clearance of ocular fibrillin-2 at the end of the
      juvenile period.

PMID- 30201141
TI  - Feeding mitochondria: Potential role of nutritional components to improve
      critical illness convalescence.
AB  - : Persistent physical impairment is frequently encountered after critical
      illness. Recent data point towards mitochondrial dysfunction as an important
      determinant of this phenomenon. This narrative review provides a comprehensive
      overview of the present knowledge of mitochondrial function during and after
      critical illness and the role and potential therapeutic applications of specific
      micronutrients to restore mitochondrial function. Increased lactate levels and
      decreased mitochondrial ATP-production are common findings during critical
      illness and considered to be associated with decreased activity of muscle
      mitochondrial complexes in the electron transfer system. Adequate nutrient levels
      are essential for mitochondrial function as several specific micronutrients play
      crucial roles in energy metabolism and ATP-production. We have addressed the role
      of B vitamins, ascorbic acid, alpha-tocopherol, selenium, zinc, coenzyme Q10,
      caffeine, melatonin, carnitine, nitrate, lipoic acid and taurine in mitochondrial
      function. B vitamins and lipoic acid are essential in the tricarboxylic acid
      cycle, while selenium, alpha-tocopherol, Coenzyme Q10, caffeine, and melatonin
      are suggested to boost the electron transfer system function. Carnitine is
      essential for fatty acid beta-oxidation. Selenium is involved in mitochondrial
      biogenesis. Notwithstanding the documented importance of several nutritional
      components for optimal mitochondrial function, at present, there are no studies
      providing directions for optimal requirements during or after critical illness
      although deficiencies of these specific micronutrients involved in mitochondrial
      metabolism are common. Considering the interplay between these specific
      micronutrients, future research should pay more attention to their combined
      supply to provide guidance for use in clinical practise. REVISION NUMBER: YCLNU-D
      17-01092R2.

PMID- 30201142
TI  - Reply - Letter to the Editor - Statistically but not clinically significant?
      Biomarkers in gastric cancer.

PMID- 30201143
TI  - Dermatoscopy: Instrumental Update.
AB  - Dermatoscopy is a noninvasive technique that allows in vivo, magnified
      observation of skin details and structures not visible to the naked eye. It may
      be performed using handheld devices or computer-assisted digital systems or
      videodermatoscopes. The handheld dermatoscope is the most used device because it
      is user-friendly and relatively inexpensive. It is not a mere magnifying glass
      but a more complex instrument that allows the visualization of the cutaneous
      microstructures of the different skin layers. Videodermatoscopes are more
      expensive systems that allow higher magnifications and simplify the process of
      image viewing, storage, organization, analysis, and retrieval.

PMID- 30201144
TI  - Dermatoscopy of Parasitic and Infectious Disorders.
AB  - The use of dermatoscopy in the diagnosis and management of parasitic and
      infectious skin disorders has been defined as entodermoscopy, and several studies
      have confirmed its advantages in dermatology. Dermatoscopic patterns of several
      parasitic, viral, and fungal skin infections have been identified and herein
      described. A noninvasive, fast, and accurate diagnosis plays an important role in
      containing the spread of contagious skin disorders.

PMID- 30201145
TI  - Dermoscopy of Common Inflammatory Disorders.
AB  - In addition to its "traditional" application for the early diagnosis of melanoma
      and nonmelanoma skin cancers, dermoscopy gains appreciation in fields beyond
      dermato-oncology. Nowadays, dermoscopy has been established as a reliable
      adjunctive tool to the everyday clinical practice of general dermatology.
      Morphology and distribution of vascular structures, background colors, follicular
      abnormalities, and the presence of scales are important features that should be
      evaluated. Clinical examination remains the undoubted mainstay of diagnosis in
      inflammatory and infectious diseases.

PMID- 30201146
TI  - Dermatoscopy of Granulomatous Disorders.
AB  - Although diagnosis of cutaneous granulomatous disorders (CGDs) is usually
      suspected based on morphologic findings, localization, and anamnestic data,
      clinical differentiation from each other and from similar dermatoses may be
      challenging. Recently, dermatoscopy has been demonstrated to be a useful tool for
      assisting the recognition of several CGDs. This article provides a current
      overview of the dermatoscopic features of the main noninfectious and infectious
      CGDs, including sarcoidosis, necrobiosis lipoidica, granuloma annulare,
      rheumatoid nodules, and leishmaniasis. Other, less common, CGDs are briefly
      addressed, including granulomatous rosacea, acne agminata, and leprosy.

PMID- 30201147
TI  - Dermoscopy of Lymphomas and Pseudolymphomas.
AB  - Primary cutaneous lymphomas are a heterogeneous group that includes 2 main groups
      of primary T- and B-cell lymphomas, which can involve the skin with distinct
      variability in clinical presentation, histopathology, immunophenotypes, molecular
      signature, and prognosis. The authors describe the most frequent clinical forms
      of cutaneous lymphomas and their dermoscopic features. Even if the diagnosis of
      these entities is still based on a cellular level and the literature on
      dermoscopy in cutaneous lymphomas is limited and, for several entities it is
      based only on single case reports/case series, we think that know how they appear
      also in dermoscopy can be useful for helping in the clinical diagnosis.

PMID- 30201148
TI  - Dermatoscopy of Vascular Lesions.
AB  - Cutaneous vascular lesions (VLs) represent a very common reason for dermatologic
      consultation for patients. In most cases, VLs are benign and self-limiting.
      However, because they often mimic malignant skin tumors, their correct and prompt
      identification is very important in daily practice. Dermoscopy may play a key
      role in achieving that purpose. This article reviews current knowledge of
      dermoscopic features of the most frequent VLs.

PMID- 30201149
TI  - Dermoscopy of Adnexal Tumors.
AB  - Cutaneous adnexal tumors include lesions with apocrine, eccrine, follicular,
      sebaceous, and mixed differentiation. Most are benign and sporadic, although
      malignant forms are occasionally observed and some cases develop in the setting
      of inherited syndromes. These tumors often cause immense diagnostic difficulty.
      Dermoscopy is a noninvasive technique that has greatly improved the diagnostic
      accuracy of different skin lesions, including these tumors. We provide a review
      of the literature on the dermoscopic structures and patterns associated with
      adnexal tumors. Most patterns associated with this kind of tumor are nonspecific
      and are observed in other nonadnexal tumors, especially in basal cell carcinomas.

PMID- 30201150
TI  - Trichoscopy Tips.
AB  - Although trichoscopy has only recently been introduced in the assessment of hair
      and scalp disorders, it is already considered an essential diagnostic tool by
      many experts in the field. This article discusses topics that are often a source
      of doubt among clinicians, and tips that may help dermatologists better perform
      trichoscopy. Subjects include fundamental concepts needed to start performing the
      method, basic trichoscopic structures, tips to identify a scarring condition and
      to approach a patient with a receding hairline, features that are unique to
      children, those that are typically seen in the dark scalp, and pitfalls of the
      technique.

PMID- 30201151
TI  - Trichoscopy in Hair Shaft Disorders.
AB  - Trichoscopy allows analyzing the structure and size of growing hair shafts in
      their natural environment in children and adults. The method replaces light
      microscopy, which requires pulling of multiple hairs for investigation. In
      monilethrix, trichoscopy shows uniform elliptical nodosities with intermittent
      constrictions. In trichorrhexis nodosa nodular thickenings along hairs shafts are
      visible (low magnification) or splitting into numerous small fibers along the
      hair shaft may be observed (high magnification). In trichorrhexis invaginata
      (bamboo hair) the hair shaft telescopes into itself at several points along the
      shaft. Trichoscopy shows small nodules along the shaft. Hairs bend and break in
      these diseases. Trichoscopy of pili torti shows twists of hair shafts along their
      long axis. In pili annulati hair shafts with alternating white and dark bands are
      visible. In woolly hair the examination demonstrates hair shafts with waves at
      very short intervals. For trichothiodystrophy polarized trichoscopy should be
      used. In ectodermal dysplasias, trichoscopy shows a variety of hair
      abnormalities, but the most characteristic finding is hair shaft pigmentation
      heterogeneity.

PMID- 30201152
TI  - Onychoscopy: Dermoscopy of the Nails.
AB  - Onychoscopy is the examination of the nail unit using a dermoscope. The
      dermoscopic criteria for a valid diagnosis have been developed and assessed in
      numerous papers. However, in all nail alterations that are suspicious or
      potentially malignant, a surgical intervention with subsequent histopathological
      evaluation should be performed. A simple visualization may not be helpful in
      diagnosing many nail conditions nor is a nail biopsy diagnostic in all cases.
      Onychoscopy is a valuable aid in enhancing visible nail features and in revealing
      cryptic features of diagnostic value.

PMID- 30201154
TI  - Dermoscopy of Inflammatory Genital Diseases: Practical Insights.
AB  - Diagnosis of genital inflammatory disorders may be difficult for several reasons,
      such as their similar appearance, possible misdiagnosis with infectious and
      malignant conditions, and peculiar anatomic conditions that may lead to
      modification of clinical features. Dermoscopy could be included as a part of the
      clinical inspection of genital diseases to support diagnosis, as well as to
      ideally avoid unnecessary invasive investigation. Practical guidance for the use
      of dermoscopy in the assessment of the main inflammatory genital diseases is
      provided, namely for lichen sclerosus, lichen planus, psoriasis, lichen simplex
      chronicus, and plasma cell mucositis.

PMID- 30201153
TI  - Dermoscopy for the Diagnosis of Conjunctival Lesions.
AB  - This article describes the present literature on dermoscopy of conjunctiva and
      shows the results of a dermoscopy study of 147 conjunctival tumors. Melanomas
      were characterized by a heavy pigmentation, irregular dots, and a higher
      prevalence of gray color compared with nevi. Squamous cell carcinomas had
      peculiar hairpin and glomerular vessels. Primary acquired melanoses were
      characterized by regularly distributed light brown dots. A large part of nevi had
      small cysts.

PMID- 30201155
TI  - Dermatoscopy of Common Lesions in Pediatric Dermatology.
AB  - The use of dermatoscopy to assist in the diagnosis of a variety of proliferative,
      pigmentary, inflammatory, infectious, congenital, and genetic cutaneous and skin
      appendage disorders is constantly increasing, as it is effective, affordable,
      noninvasive, and quick to perform.

PMID- 30201156
TI  - Dermoscopy of Pigmentary Disorders in Brown Skin.
AB  - Dermoscopy is a noninvasive technique for the diagnosis, prognosis, and
      monitoring of pigmentary disorders in brown skin. It can be used for the
      diagnosis of various facial melanoses, which can avoid the need for biopsy in
      many cases. It can also help in early identification of the adverse effect of
      topical steroids and hydroquinone when they are used for the treatment of these
      disorders. Dermoscopy can also reliably differentiate vitiligo from other
      disorders of hypopigmentation. It can also help in assessing the stability of
      vitiligo before surgery.

PMID- 30201157
TI  - Dermatoscopy and Reflectance Confocal Microscopy Correlations in Nonmelanocytic
      Disorders.
AB  - Dermatoscopy and in vivo reflectance confocal microscopy are noninvasive
      techniques that provide a horizontal approach, with an en face view of the skin
      structures. Both techniques assist in the clinical diagnosis of a variety of
      inflammatory and infectious cutaneous disorders. In many cases, they have shown
      concordance. Their combined use represents, in several instances, a promising
      option to reach the final diagnosis without the need for invasive procedures.

PMID- 30201158
TI  - The Expanding Use of Dermatoscopy.

PMID- 30201159
TI  - A Patch Testing Initiative for the Investigation of Allergic Contact Dermatitis
      in a UK Allergy Practice: A Retrospective Study.
AB  - BACKGROUND: Patch testing is the gold standard diagnostic tool for investigating
      allergic contact dermatitis (ACD). In the United Kingdom, patch testing has been
      historically confined to the dermatologist's office. Furthermore, detailed
      studies on patch testing by allergists are significantly underrepresented at the
      international level. OBJECTIVE: The objective of this study was to undertake a
      comprehensive evaluation of a patch testing initiative from an allergy practice;
      we report on various patient characteristics, prevalence and relevance data, in
      addition to immediate hypersensitivity testing. METHODS: We undertook a
      retrospective analysis of 156 patients suspected of having contact dermatitis
      seen in our UK allergy practice between October 2016 and April 2018. RESULTS: Of
      the 156 patients patch tested (mean age 36.9 years, female 88%, white ethnicity
      71.8%, atopy 68.6%), ACD was diagnosed overall in 49% of the cohort and ACD of
      current relevance was assigned to 31%. Our extended British standard series alone
      detected the responsible allergen in 87% of patients, and the remaining 13% were
      detected from supplementary or own material testing alone. Most prevalent contact
      allergens were nickel (28.2%), p-phenylenediamine (8.3%), cobalt (8.3%),
      methylisothiazolinone (5.8%), and hydroperoxides of linalool (4.5%) and limonene
      (4.5%). A history of occupationally related dermatitis (P = .004) and initial
      (pretest) diagnosis of ACD (P < .001) were both significantly associated with
      relevant positive patch test reactions (atopy status was not associated P > .05).
      CONCLUSIONS: ACD was detected in almost 50% of assessed patients, and we
      highlight the importance of assessing relevance. Hydroperoxides of limonene and
      linalool are notable additions to the prevalence data. Patch testing should be
      incorporated into more allergy practices, although availability of training is a
      limiting factor.

PMID- 30201160
TI  - Implementing Health Care Technology Research into Practice to Improve Adult
      Asthma Management.
AB  - BACKGROUND: Use of health technology has shown potential to improve asthma
      adherence and outcomes. Few studies have looked at the implementation of such
      research within larger asthma populations. OBJECTIVE: This report examines the
      process of translating results from a pragmatic trial using speech recognition
      (SR) in children with persistent asthma into the standard operating procedure
      within a large health maintenance organization. Medication adherence and outcomes
      in adults with asthma were examined. METHODS: The SR protocol was implemented for
      the total Kaiser Permanente Colorado (KPCO) patient population of 480,142, of
      whom 36,356 had asthma. Patients had persistent asthma, filled 1 or more inhaled
      corticosteroid prescriptions in the prior 6 months, and remained continuously
      enrolled with KPCO for 2 years. Documented exacerbations included the presence of
      a hospitalization, emergency department visit, or course of oral corticosteroid
      where asthma was the principal diagnosis. Adherence and exacerbation events were
      compared 1 year before and 1 year after intervention for 4,510 adults aged 19 to
      64. RESULTS: Patient adherence demonstrated a small but significant improvement
      from 39.5% to 41.7% (P < .0001). Although not significant, data trends suggested
      greater improvement for patients with lower socioeconomic status. When an outlier
      month was removed from both the pre- and postintervention time periods, courses
      of oral corticosteroids decreased. Emergency department visits and
      hospitalizations were infrequent in both time periods and did not decrease over
      time. CONCLUSIONS: A low-cost SR intervention reminding patients to fill and take
      their daily controller asthma medication can improve treatment adherence and
      decrease the need for oral corticosteroids due to asthma exacerbations, but not
      decrease emergency department visits or hospitalizations.

PMID- 30201161
TI  - Determination of glyoxal and methylglyoxal in atmospheric fine particulate matter
      by vortex-assisted micro-solid phase extraction and liquid chromatography-diode
      array detection.
AB  - Determination of alpha-dicarbonyl compounds, glyoxal (Gly) and methyl glyoxal
      (Mgly), in atmospheric fine particulate matter PM2.5 (particulate matter with an
      aerodynamic diameter of less than 2.5 MUm) which play vital roles in generating
      secondary organic aerosols in the ambient air, was carried out by vortex-assisted
      micro-solid phase extraction (VA-MU-SPE)-liquid chromatography-diode array
      detection (LC-DAD), with on-sorbent derivatization by 2,4-dinitrophenylhydrazine
      (DNPH). This is the first time such an approach of combining on-sorbent
      derivatization and extraction in one step together with LC analysis has been
      applied to PM2.5. Extraction parameters such as selection of sorbent, extraction
      time, desorption time and sample volume were optimized using water samples spiked
      with Gly and Mgly. Under the most favourable conditions, good intra- (1.39%
      2.78%) and inter-day (2.29%-6.56%) precision and linearity (ranging between 0.5
      and 100 ng mL-1) along with coefficients of determination 0.998 and 0.997, were
      determined. The limits of detection were determined to be 0.14 ng mL-1
      (derivatized Gly) and 0.15 ng mL-1 (derivatized Mgly) whereas the limits of
      quantification were 0.47 ng mL-1 and 0.50 ng mL-1, respectively. The developed
      method was successfully employed to the determination of Gly and Mgly associated
      with PM2.5. The latter was collected on glass fiber filters which were immersed
      in methanol: water (1:1 v/v) for MU-SPE, which was conducted using a sorbent pre
      coated with DNPH. The concentrations of the Gly and Mgly were determined to be
      0.38 ng m-3 and 0.41 ng m-3 in the sampled ambient air, with relative recoveries
      of between 69-97%.

PMID- 30201162
TI  - Development and applications of solid-phase extraction and liquid chromatography
      mass spectrometry methods for quantification of microcystins in urine, plasma,
      and serum.
AB  - The protocols for solid-phase extraction (SPE) of six microcystins (MCs; MC-LR,
      MC-RR, MC-LA, MC-LF, MC-LW, and MC-YR) from mouse urine, mouse plasma, and human
      serum are reported. The quantification of those MCs in biofluids was achieved
      using HPLC-orbitrap-MS in selected-ion monitoring (SIM) mode, and MCs in urine
      samples were also quantified by ultra-HPLC-triple quadrupole-tandem mass
      spectrometry (UHPLC-QqQ-MS/MS) in multiple reaction monitoring (MRM) mode. Under
      optimal conditions, the extraction recoveries of MCs from samples spiked at two
      different concentrations (1 MUg/L and 10 MUg/L) ranged from 90.4% to 104.3% with
      relative standard deviations (RSDs) <= 4.7% for mouse urine, 90.4-106.9% with
      RSDs <= 6.3% for mouse plasma, and 90.0-104.8% with RSDs <= 5.0% for human serum.
      Matrix-matched internal standard calibration curves were linear with R2 >= 0.9950
      for MC-LR, MC-RR and MC-YR, and R2 >= 0.9883 for MC-LA, MC-LF, and MC-LW. The
      limits of quantification (LOQs) in spiked urine samples were ~0.13 MUg/L for MC
      LR, MC-RR, and MC-YR, and ~0.50 MUg/L for MC-LA, MC-LF, and MC-LW, while the LOQs
      in spiked plasma and serum were ~0.25 MUg/L for MC-LR, MC-RR, and MC-YR, and
      ~1.00 MUg/L for MC-LA, MC-LF, and MC-LW. The developed methods were applied in a
      proof-of-concept study to quantify urinary and blood concentrations of MC-LR
      after oral administration to mice. The urine of mice administered 50 MUg of MC-LR
      per kg bodyweight contained on average 1.30 MUg/L of MC-LR (n = 8), while mice
      administered 100 MUg of MC-LR per kg bodyweight had average MC-LR concentration
      of 2.82 MUg/L (n = 8). MC-LR was also quantified in the plasma of the same mice.
      The results showed that increased MC-LR dosage led to larger urinary and plasma
      MC-LR concentrations and the developed methods were effective for the
      quantification of MCs in mouse biofluids.

PMID- 30201164
TI  - The accuracy of virtual-surgical-planning-assisted treatment of hemifacial
      microsomia in adult patients: distraction osteogenesis vs. orthognathic surgery.
AB  - Hemifacial microsomia (HFM) is a common congenital craniofacial deformity with a
      high prevalence. Orthognathic surgery and distraction osteogenesis are two
      conventionally used treatments of HFM. The main objective of this retrospective
      study was to evaluate the accuracy of two treatments with the help of virtual
      surgical planning in adult HFM patients. Sixty-eight adult patients with
      unilateral HFM were enrolled in this study. Preoperative surgical planning and
      simulation were performed on three-dimensional computed tomography models.
      Orthognathic surgery or distraction osteogenesis was performed under the guidance
      of three-dimensional surgical templates. Postoperative evaluation of the
      intervention was performed by comparison of the affected ramus height, chin
      deviation and the occlusal cant in surgical planning and actual result. Outcome
      and feedback information (an average of 14 months) showed that virtual surgical
      planning was accurately transferred to actual surgery in both surgical
      approaches. There were no statistical differences between the accuracy of
      affected ramus height and the occlusal cant in two surgical approaches. The
      orthognathic group showed significantly higher accuracy in chin deviation. In
      conclusion, virtual surgical planning and three-dimensional surgical templates
      were proved to facilitate treatment planning and offer an accurate surgical
      result in the treatment of adult HFM patients.

PMID- 30201163
TI  - Preparation and application of a restricted access material with hybrid
      poly(glycerol mono-methacrylate) and cross-linked bovine serum albumin as
      hydrophilic out layers for directly on-line high performance liquid
      chromatography analysis of enrofloxacin and gatifloxacin in milk samples.
AB  - A novel restricted access material (RAM) was prepared through combination of
      hydrophilic polymer poly(glycerol mono-methacrylate) and cross-linking bovine
      serum albumin (BSA) for direct biological analysis. In the material preparation,
      the poly(styrene-co-divinylbenzene) and poly(glycerol mono-methacrylate) were
      grafted on silica successively by atom transfer radical polymerization. Then the
      BSA was adsorbed on the material and cross-linked through an in-column process.
      The BSA recoveries of the resulted RAM were higher than 99.3%. Small molecules
      such as alkylbenzene and quinolone antibiotics could be retained with a reversed
      phase mechanism. The column packed with RAM had good long term stability and
      could last at least five months without significantly changed in its
      efficiencies. An on-line SPE/HPLC method for the analysis of enrofloxacin and
      gatifloxacin in milk samples was established by using the resulted RAM as the
      solid-phase extraction material. The detection and quantitation limits of two
      antibiotics were 8.22 and 27.4 ng mL-1, respectively. In the method validation,
      least recovery 88.5% with relative standard deviation of less than 3.9% was
      obtained. It demonstrated that the method is reliable and the material can be
      used for the direct analysis of veterinary drug residues in biological samples.

PMID- 30201165
TI  - Etiology of Shoulder Arthritis in Young Patients.
AB  - The manifestation of glenohumeral arthritis in the young adult is a devastating
      occurrence that can be difficult to manage. This review details the many
      underlying etiologies including genetic causes, congenital abnormalities,
      glenohumeral instability, posttraumatic lesions, postcapsulorraphy arthropathy,
      osteonecrosis, intraarticular pain pump postoperative use, radiofrequency/thermal
      capsulorraphy treatments, septic arthritis/infection, and inflammatory
      arthropathies. Although each of these potential causes have been well-studied,
      their contributions to the development of glenohumeral arthritis in the young
      person has not been described extensively.

PMID- 30201166
TI  - Nonarthroplasty Options for the Athlete or Active Individual with Shoulder
      Osteoarthritis.
AB  - The management of glenohumeral osteoarthritis is difficult in young, active
      individuals. After nonoperative management fails, arthroscopic debridement with
      concomitant procedures (eg, loose body removal, capsular release, labral
      debridement, synovectomy, osteophyte resection, bursectomy, subacromial
      decompression, microfracture, and biceps tenotomy or tenodesis) to address
      potential pain generators may be an option in small, contained, unipolar lesions.

PMID- 30201167
TI  - The Role for Shoulder Hemiarthroplasty in the Young, Active Patient.
AB  - Younger patients with severe glenohumeral (GH) arthritis are a challenge to
      treat, as they have high physical demands, high expectations, a long lifespan,
      and often altered anatomy from prior surgery or congenital deformity.
      Nonoperative management is the cornerstone of treatment; however, when it fails,
      shoulder arthroplasty can be indicated. Although the literature suggests that
      total shoulder arthroplasty is the most appropriate for severe GH arthritis,
      there are a subset of patients in which a hemiarthroplasty can still be
      successful. This article reviews the clinical performance of hemiarthroplasty in
      patients with specific diagnoses while highlighting the limitations of the
      operation.

PMID- 30201168
TI  - Biologic Options for Glenohumeral Arthritis.
AB  - Biologic options for glenohumeral arthritis include intra-articular injections as
      well as allograft interposition arthroplasty. The objectives of these treatments
      are reduction of pain and maintenance/improvement in function, while delaying the
      need for arthroplasty. This article reviews the current evidence for hyaluronic
      acid injection, platelet-rich plasma injection, and allograft interposition
      arthroplasty in the young patient with glenohumeral arthritis.

PMID- 30201169
TI  - Total Shoulder Arthroplasty in the Athlete and Active Individual.
AB  - Shoulder arthroplasty is becoming more commonly performed in the United States.
      As it increases, the population also becomes younger, and their demands are
      different from the older population. Earlier studies have suggested that although
      young patients have functional outcomes similar to older patients, their
      satisfaction scores were not as high. Recent literature has demonstrated that
      young or active individuals with a total shoulder arthroplasty (TSA) have good
      return rates to sports. Hemiarthroplasty and reverse shoulder arthroplasty, when
      compared with TSA, have lower but also reasonable return rates to sports.

PMID- 30201170
TI  - Subscapularis-Sparing Approaches to Total Shoulder Arthroplasty: Ready for Prime
      Time?
AB  - To minimize the risk of subscapularis failure after shoulder replacement, a
      method of preserving the subscapularis while allowing access to the glenohumeral
      joint was developed. Only the inferior 30% to 50% of the subscapularis tendon is
      detached from the humerus, leaving the superior aspect attached to the lesser
      tuberosity. This subscapularis-sparing, minimally invasive approach to the
      glenohumeral joint was evaluated in 43 subjects with a minimum 2-year follow-up
      and subscapularis strength equal to the opposite side. The approach provided
      adequate exposure for shoulder replacement surgery and decreased risk of
      postoperative failure of the subscapularis tendon.

PMID- 30201171
TI  - Rehabilitation Strategies After Shoulder Arthroplasty in Young and Active
      Patients.
AB  - A well-designed and sensibly progressed rehabilitation program is vital to
      successful shoulder arthroplasty outcomes. This article describes the protocol
      suggested by ONS clinicians to treat the growing young, active patient population
      undergoing anatomic shoulder arthroplasty. This protocol includes an immediate
      postoperative phase, early strengthening phase, resistance strengthening and
      proprioception phase, and advanced sport-specific and goal-specific strengthening
      and proprioception phase. These patients may progress more quickly than older
      patients and require more challenging exercises aimed at regaining strength and
      mobility for activity, thus this protocol emphasizes incorporating full-body
      training to prevent undue stress on the repair on return to activity.

PMID- 30201172
TI  - Return to Play After Shoulder Replacement Surgery: What Is Realistic and What
      Does the Evidence Tell Us.
AB  - This article analyzes the available literature regarding return to sport
      following total shoulder arthroplasty (TSA), hemiarthroplasty (HA), and reverse
      shoulder arthroplasty (RTSA). It examines the quality of the available evidence
      and areas of future research. Most patients are able to return to preoperative
      sport activities following TSA, RTSA, and HA. The rates of return for TSA are
      slightly higher than those reported for HA and RTSA. Patients may be counseled
      that noncontact, low-demand activities have higher return rates. Most patients
      can expect to return to sports within 6 months postoperatively.

PMID- 30201173
TI  - Outcomes After Shoulder Replacement Surgery in the Young Patient: How Do They Do
      and How Long Can We Expect Them to Last?
AB  - Glenohumeral arthritis in the young, active patient remains a challenging problem
      shoulder surgeons face. Anatomic total shoulder arthroplasty has been proven to
      be a successful operation for patients with end-stage shoulder arthritis;
      however, concerns over long-term implant survival remain. These concerns are
      amplified in young patients and largely revolve around the placement of a glenoid
      component, which is seen as the "weak link" in shoulder arthroplasty. Here we
      discuss the reported outcomes and survivorship of the different shoulder
      arthroplasty options in young patients.

PMID- 30201174
TI  - Future Frontiers in Shoulder Arthroplasty and the Management of Shoulder
      Osteoarthritis.
AB  - Shoulder arthroplasty has advanced considerably in recent decades, but the most
      recently published long-term outcomes continue to have unacceptably high failure
      rates, especially in young patients. However, there are several future frontiers
      that offer the promise of improved implant longevity and function including
      advances in surgical approach, such as subscapularis-sparing approaches and
      computer-assisted surgical planning; advances in humeral component fixation, such
      as stemless, short-stem, and convertible implants; advances in bearing surfaces,
      such as pyrocarbon, ceramic, and metal-on-metal; and advances in glenoid
      component geometry and fixation, such as augmented components, in-growth pegs,
      and inlay glenoid components.

PMID- 30201175
TI  - Foreword.

PMID- 30201176
TI  - Shoulder Arthritis in the Young and Active Patient.

PMID- 30201177
TI  - Bronchial Artery Pseudoaneurysm After Right Upper Lobectomy. An Exceptional Case.

PMID- 30201178
TI  - Letter to editor regarding "Surgical approaches for open reduction and internal
      fixation of intra-articular distal humerus fractures in adults: A systematic
      review and meta-analysis".

PMID- 30201179
TI  - Letter to the editor regarding "Single versus double column fixation in
      transverse fractures of the acetabulum: A randomised controlled trial".

PMID- 30201180
TI  - Neural Circuits for Goal-Directed Sensorimotor Transformations.
AB  - Precisely wired neuronal circuits process sensory information in a learning- and
      context-dependent manner in order to govern behavior. Simple sensory decision
      making tasks in rodents are now beginning to reveal the contributions of distinct
      cell types and brain regions participating in the conversion of sensory
      information into learned goal-directed motor output. Task learning is accompanied
      by target-specific routing of sensory information to specific downstream cortical
      regions, with higher-order cortical regions such as the posterior parietal
      cortex, medial prefrontal cortex, and hippocampus appearing to play important
      roles in learning- and context-dependent processing of sensory input. An
      important challenge for future research is to connect cell-type-specific activity
      in these brain regions with motor neurons responsible for action initiation.

PMID- 30201181
TI  - [Contained rupture of the non-coronary sinus of Valsalva aneurysm into the right
      atrium (Sakakibara type IV) treated by surgery].
AB  - A 26-year-old woman of Cap Verdean origin was admitted to emergency unit with
      chest pain and dyspnea. Because of sinus tachycardia without any other
      electrocardiogram abnormalities, high NT-pro BNP level, and weakly positive
      cardiac troponin I and D-dimer levels, an aortic and pulmonary non ECG-gated CT
      angiography was performed that excluded pulmonary embolism and aortic dissection.
      Transthoracic echocardiography (TTE) showed a contained rupture of the non
      coronary sinus of Valsalva aneurysm sized 23 to 24mm into the right atrium.
      According to the high rupture risk, patient had been immediately transferred in a
      cardiologic surgical center where transesophageal echocardiography (TEE) and
      thoracic angiography ECG-gated Multiple Detector Computerized Tomography (ECG
      gated MDCT) reinforced the diagnosis. Patient underwent surgical repair resection
      of the aneurysmal sac, which was described as "tissue paper thin" and at risk for
      impending rupture, without evidence of communication between the aorta and the
      right atrium. Anatomopathological examination described a thick sclerotic and
      oedematous aneurysm wall without inflammation, and bacteriological examination
      was negative. It is a rare case of contained rupture of the congenital non
      coronary sinus of Valsalva aneurysm into the right atrium (Type IV of Sakakibara
      classification), with a high rupture risk. This case shows that the use ECG-gated
      MDCT is more appropriate when aortic dissection is suspected, allowing a detailed
      analysis of aorta, especially the proximal portion which is more susceptible to
      motion artifacts.

PMID- 30201182
TI  - Applying the neonatal Early-Onset Sepsis calculator in cases of clinical
      chorioamnionitis at or after 34 weeks of gestation.

PMID- 30201183
TI  - Longitudinal Self-Management and/or Transition Readiness per the TRxANSITION
      Index among Patients with Chronic Conditions in Pediatric or Adult Care Settings.
AB  - OBJECTIVE: To evaluate the roles of key individual, family, and illness
      characteristics on the levels of and gains in longitudinal healthcare transition
      (HCT) readiness in the pediatric setting and/or self-management skills (SMS) in
      the adult-focused setting, we used a large dataset with longitudinal measurements
      from 2006 to 2015. STUDY DESIGN: This longitudinal observational study followed
      566 adolescents and young adults with chronic conditions at University of North
      Carolina Hospitals. TRxANSITION Index measurements, which represent learning
      outcomes rather than health outcomes, were collected multiple times per patient
      and analyzed using a novel application of an education-based approach. RESULTS:
      Levels of and gains in HCT/SMS scores increased with age (P < .001) with smaller
      increases at older ages. Mastery of skills varied by age with self-management
      achieved after 20 years of age. Scores varied positively by father's education
      and negatively by mother's education and duration of diagnosis. Gains in scores
      further varied positively with private insurance and negatively with mother's
      education and duration of diagnosis. CONCLUSIONS: We found diminishing positive
      increases in HCT/SMS scores as patients become older and smaller levels of and
      gains in readiness among younger patients with more educated mothers. Risk
      factors for absolute level of HCT/SMS readiness and inadequate longitudinal gains
      are not always the same, which motivates a deeper understanding of this dynamic
      process through additional research. This information can guide providers to
      focus HCT/SMS preparation efforts on skills mastered at particular ages and to
      identify patients at risk for inadequate development of HCT/SMS skills.

PMID- 30201184
TI  - Perceptions of pharmacists and physicians on generic substitution in a financial
      crisis context in Northwestern Spain: A qualitative study.
AB  - : In Spain, the use of generics has considerably evolved in a short period of
      time through different anti-crisis legislation changes. Before the financial
      crisis the proposal of generics was an option for patients. Nowadays its use is
      actively enforced by Health authorities. OBJECTIVE: To explore the perceptions of
      pharmacists and physicians regarding the generic substitution driven by new
      Spanish drugs policies as well as their adaptive strategies intended to lessen
      the impact of changes to their patients' treatment. METHODS: Pharmacists (16) and
      physicians (13) from Ferrol and A Coruna participated in a qualitative study
      using semi-structured in-depth interviews. RESULTS: Qualitative analysis allowed
      identification of nine key components in the substitution process: Enabling
      factors: 'Adequate information to patients', 'Acute treatments', 'Bioappearance',
      'Prescription by Estate Official Denomination followed by laboratory name',
      'Personalized dosage systems'. Obstructing factors: 'Generics/Authorities
      distrust', 'Lack of time', 'Patient characteristics', 'Pharmacy financial
      management'. CONCLUSIONS: Pharmacists and physicians in our economic crisis
      context perceive different barriers resulting in difficulties in the generic
      substitution process. They have implemented strategies to capitalize on the
      enablers and overcome the additional budget-cut barriers imposed by the
      Administration that had prevented them from maintaining their patient's treatment
      preferences. Spanish health authorities could improve current legislation either
      by reducing the number of new laboratories of authorized generic manufacturers or
      by extending the pharmacist capability for equivalent drugs substitution.

PMID- 30201185
TI  - Strengthening primary care: The Veneto Region's model of the Integrated Medical
      Group.
AB  - PURPOSE: This paper aims to illustrate the development of the Veneto Region's
      (Italy) new primary care model and to report on the preliminary results.
      BACKGROUND: Achieving integrated management and continuity of care are the two
      main aims of the Veneto Region's health planning legislation for 2012-2016. Under
      this framework, and to meet new emerging population needs, it has become
      necessary to adopt a new primary care model that embraces multi-professional
      teams. In response the Veneto Region has developed the Integrated Medical Group
      (IMG), launched in 2016. The Integrated Medical Group is an innovative model at
      both the regional and national level and represents a key element of the health
      care system. It targets several goals: it provides more effective care than in
      the past; guarantees services within the region while optimizing the use of
      resources, through integrated patient care and its accompanying care pathways; it
      builds dialogue between hospitals and community based primary care services;
      develops relationships of trust between doctors and patients, pursuing shared
      team goals and enhances the different skills and roles of their constituent
      members. Regional legislation sets challenging objectives, stating that by the
      end 2017, 60% of all GPs in the region should conduct their activities as part of
      an IMG, with a further target of 80% by the end 2018.

PMID- 30201186
TI  - Fertility-enhancing agents.

PMID- 30201187
TI  - Does continued aspirin mono-therapy lead to a higher bleeding risk after total
      knee arthroplasty?
AB  - BACKGROUND: Evidence about the risk of bleeding and thromboembolism because of
      aspirin mono-therapy in total knee arthroplasty (TKA) is scant. We wanted to
      validate the risks of bleeding and thromboembolism with continued aspirin mono
      therapy in unilateral and simultaneous bilateral TKA. METHODS: We enrolled a
      series of 1655 patients who underwent unilateral or simultaneous bilateral TKA
      between December 2010 and December 2012. Drainage amount, postoperative
      hemoglobin level, change in hemoglobin, calculated blood loss, incidence and the
      amount of blood transfused, and the proportion of thromboembolic events were
      compared between patients who were and patients who were not on continued aspirin
      mono-therapy. RESULTS: Calculated blood loss (969.1 +/- 324.9 vs. 904.0 +/- 315.5
      ml), transfusion amounts (1.3 +/- 1.5 vs. 1.0 +/- 1.3 IU), and percentage of
      transfused patients (53.0% vs. 40.2%) were higher in unilateral TKA patients on
      continued aspirin mono-therapy. Outcome parameters and the proportion of DVT
      between groups were not significantly different. One patient (0.3%) not on
      aspirin mono-therapy developed a pulmonary embolism, and two others (0.6%) had
      cerebrovascular events. CONCLUSION: Despite the slightly higher risks of
      bleeding, continuing aspirin mono-therapy during TKA might be safe with low risks
      of perioperative cerebrovascular, cardiovascular, and venous thromboembolic
      events.

PMID- 30201188
TI  - Correlation between lower uterine wall thickness measured by transabdominal
      ultrasonography and cervical length measured by transvaginal ultrasonography in
      Thai pregnant women.
AB  - BACKGROUND: Preterm labor is one of major obstetric challenges and can be
      predicted by cervical length at mid-trimester. In some settings, transvaginal
      ultrasound is not available and the screening and prevention of preterm labor
      will be suboptimal. We hope to find a correlation between other marker i.e. lower
      uterine wall thickness measured by transabdominal ultrasonography and cervical
      length measured by transvaginal ultrasonography in Thai pregnant women during 16
      32 weeks of gestation. METHODS: This study was a cross-sectional study. 166
      singleton pregnant women were invited to participate in the study between June
      2015 and December 2015. Transabdominal ultrasonography was performed to measure
      the lower uterine wall thickness and transvaginal ultrasonography was performed
      to measure the cervical length. The Spearman's rank correlation was used to
      evaluate the correlation between the two parameters. The inter-observer variation
      was assessed by using Bland-Altman plot. The outcomes of all pregnancies were
      followed and only those who delivered at term were included for the calculation
      of normal value of lower uterine wall thickness. RESULTS: There was a highly
      positive correlation between lower uterine wall thickness and cervical length (rs
      = 0.767, n = 166, p < 0.001). For those who had short cervical length (defined as
      less than 30 mm) at GA 16-24 weeks (n = 10), the mean corresponding lower uterine
      wall thickness was 4.4 mm (SD 0.50). The inter-observer variation of the
      measurement of lower uterine wall thickness and cervical length were small. The
      lower uterine wall thickness tended to be slightly thinner when the gestation
      advanced. (mean 5.4 mm at 16-20 weeks and 5.1 mm at 28-32 weeks). CONCLUSION:
      There was a highly positive correlation between lower uterine wall thickness
      measured by transabdominal ultrasonography and cervical length measured by
      transvaginal ultrasonography in Thai pregnant women.

PMID- 30201189
TI  - Huperzine-A response to cognitive impairment and task switching deficits in
      patients with Alzheimer's disease.
AB  - BACKGROUND: Alzheimer's Disease (AD) is associated with cognitive decline due to
      various pathological mechanisms. There are several acetylcholinesterase inhibitor
      compounds which can improve cognition, but Huperzine-A is a natural sesquiterpene
      alkaloid extracted from Chinese herb (Huperzia Serrata) which has rapid action.
      METHODS: Double blind study was conducted. Participants included 50 patients with
      AD and 50 healthy individuals. Patients were recruited from Civil and BV hospital
      Bahawalpur and Nishter hospital Multan, Pakistan during May 2017 until February
      2018 who were stable on Huperzine-A medication. Patients were tested twice.
      First, at the time of diagnosis to determine baseline scores. Second, post eight
      weeks of Huperzine-A treatment. Healthy individuals had single testing session.
      Participants completed Addenbrooke's Cognitive Examination and Trail Making Test.
      RESULTS: Patients with AD showed cognitive and task switching deficits in
      contrast with healthy individuals. There was significant improvement in cognition
      and task switching abilities post Huperzine-A treatment compared with baseline
      performance. CONCLUSION: Huperzine-A is effective in reducing cognitive and task
      switching deficits in patients with AD.

PMID- 30201190
TI  - Reply.

PMID- 30201191
TI  - Hepatitis B: From control to cure.

PMID- 30201192
TI  - Yet another humanitarian crisis involving innocent children.

PMID- 30201193
TI  - Knowledge on types of treatment pressure. A cross-sectional study among mental
      health professionals.
AB  - Treatment pressure restricts patients' voluntary and autonomous decisions. Yet
      interventions involving treatment pressure are widely used in mental health and
      psychosocial services. This cross-sectional study explored whether mental health
      professionals' knowledge on five types of treatment pressure (no coercion,
      persuasion or conviction, leverage, threat, and formal coercion) was associated
      with sociodemographic, professional and contextual factors. A more positive
      attitude towards interventions involving treatment pressure was associated with
      underrating the level of those interventions compared with a predefined default
      value. The treatment setting and professional group played a minor role in
      'leverage' and 'formal coercion' types of treatment pressure, respectively.

PMID- 30201194
TI  - Predictors of marital adjustment among child brides.
AB  - The researchers aim was to examine the predictors of marital adjustment among
      child brides in Turkey. The sample included 246 women who were between 18 and 49
      years of age, got married while under the age of 18, not divorced, who spoke
      Turkish or Kurdish, by using convenience sampling method. We used a marital
      adjustment scale and a survey form to collect data. Our findings indicated that
      marital adjustment was low among child brides. The factors affecting women's
      marital adjustment were duration and types of the marriage, number of pregnancies
      and physical violence. The incidence of physical violence was inversely
      correlated with the scores of marital adjustment of women, while the women's age,
      education, income level, number of living children, age, and the education level
      of their partner was not correlated. The results of this study would be useful
      for nurses, midwives, social workers, and counselors who assist women who are
      facing domestic violence.

PMID- 30201195
TI  - Perceptions of professional role in community mental health nurses: The interplay
      of power relations between nurses and mentally ill individuals.
AB  - Nurses' professional role perception is related to the quality and safety of
      care. Limited data exist regarding professional role perception in community
      mental health nurses (CMHNs). The aim of the present study was to investigate the
      living experience of Greek-Cypriot CMHNs of their professional role. A
      phenomenological approach based on Munhall's methodology was applied. According
      to purposive sampling, five Greek-Cypriot CMHNs participated, following informed
      consent. The interplay of power relations between participants and mentally ill
      individuals during CMHNs' house calls was revealed as the core theme contributing
      to the perception of their status within their professional role. Participants'
      perception of their status as visitors in patients' homes rather than
      authoritative figures, an image held within hospital mental health services, was
      deemed as the greatest challenge of their professional role. Moreover, the
      necessity for autonomous and rapid decision-making during home visits was
      described as an absolute prerequisite for professional effectiveness. Overall,
      the main themes were grouped as follows: professional role perceptions,
      perception of self within professional role, feelings and expectations about
      professional role. Non-power relations between participants and patients, along
      with efficacy, control and adequate clinical autonomy for effective professional
      practice were highlighted as major prerequisites during house calls.
      Interventions towards nurses' psychosocial and organizational empowerment, as
      well as strengthening patients' self-determination are proposed.

PMID- 30201196
TI  - Evaluation of depression in patients with alzheimer's disease according to the
      location of medical care.

PMID- 30201197
TI  - Service users' views regarding user involvement in mental health services: A
      qualitative study.
AB  - BACKGROUND: Service user involvement is emphasised in many strategies, plans and
      declarations globally. However, in practice, service user involvement is not
      always achieved and remains at a tokenistic level. OBJECTIVES: To explore the
      views of service users on user involvement in mental health service. DESIGN:
      Explorative descriptive study design. SETTING: The study was conducted in one
      psychiatric hospital and in two mental health organisations in western Finland.
      METHODS: The data was generated through three focus group interviews and analysed
      with qualitative content analysis. RESULTS: User involvement means that people
      using mental health services are respected, listened to and can act in co
      operation with professionals so than they feel that they can influence their own
      care and treatment. The participants articulated concrete factors that promote or
      inhibit user involvement. Service user involvement can be enhanced by
      strengthening service users' position, by developing the mental health care
      system and by specific training for professionals. CONCLUSIONS: The views of
      service users in this study concerning the realisation of user involvement and
      the factors promoting and preventing it were realistic. They are basic elements
      of patient-centred care and of all human interaction. Our participants described
      service user involvement in their own care and treatment. They emphasised the
      need to have more information, and wanted to be more involved in decision-making
      about their own care and treatment. They called for better care planning and co
      ordination as one way to increase service user involvement. These also have
      implications for mental health services at the system level.

PMID- 30201198
TI  - Using instrumentation in psychiatric nursing to assess documentation of the
      nursing process for emergent non-psychiatric patient events.
AB  - Ongoing education of experienced psychiatric nurses is imperative given the
      historically complex health presentations of psychiatric patients. Psychiatric
      patients tend to have medical co-morbidities and often do not have the financial
      resources for preventative health care. The hospitalization for acute psychiatric
      stabilization, is an opportunity for psychiatric nurses to teach and advocate for
      patients' physiological and psychological health. Documentation of patients'
      changes in condition and overall clinical presentation, is necessary to ensure
      patients' health care needs are met.

PMID- 30201199
TI  - Care-planning and decision-making for youth with mental health needs in the
      foster care system.

PMID- 30201200
TI  - Is it safe? The restraint chair compared to traditional methods of restraint: A
      three hospital study.

PMID- 30201201
TI  - Improving the practice of handover for psychiatric inpatient nursing staff.
AB  - AIM: The aim of this project was to embed SBAR as a communication framework into
      inpatient point of care nurses handover practices on 27 inpatient psychiatric
      units, and to ensure that the information given/received provided staff with the
      confidence to provide safe patient care. METHODS: A plan-do-study-act quality
      improvement framework was used to improve the adoption of SBAR in practice.
      Resources were developed that were relevant to the psychiatric setting; staff
      were educated, audits and a survey were completed. RESULTS: The use of SBAR in
      practice increased from 4% pre intervention to 79% post intervention.
      Satisfaction with the information received during handover increased from 34% to
      41%. CONCLUSION: Findings of this project demonstrate that the standardization of
      handover practices and the implementation of a consistent communication framework
      across the organization can improve the effectiveness of shift handover, increase
      staff satisfaction, and improve safety of both staff and patients.

PMID- 30201202
TI  - The effect of mindfulness-based psychoeducation on insight and medication
      adherence of schizophrenia patients.
AB  - PURPOSE: This research was conducted to determine the effect of mindfulness based
      psychoeducation program on insight and medication adherence of schizophrenia
      patients. MATERIALS AND METHODS: The study was conducted in a true experiment
      design with pre-test and post-test control groups. The study population consisted
      of 369 schizophrenic patients enrolled in Community Mental Health Centers located
      in Balikesir and Eskisehir province centers. The sample consisted of 135
      patients, 55 from experimental and 80 from control groups selected by randomized
      sampling. The data was collected between February and May 2016. The Descriptive
      Information Form, Beck Cognitive Insight Scale (BCIS) and Medication Adherence
      Rating Scale (MARS) were used. In the experimental group, the psychoeducation
      program was applied. Number, percentage, mean, standard deviation, chi-square, t
      test in both dependent and independent groups, were used in the analysis of the
      data. RESULTS: The mean post-test score of the Beck Cognitive Insight Scale was
      4.89 +/- 6.05 in the experimental group, 1.68 +/- 5.67 in the control group and
      the difference between the mean scores was statistically significant (p < 0.05).
      The mean post-test score of Medication Adherence Rating Scale was 1.76 +/- 0.42
      in the experimental group, 1.50 +/- 0.50 in the control group and the difference
      between the mean scores was statistically significant (p < 0.05). CONCLUSION: It
      was determined that psychoeducation program was effective in increasing cognitive
      insight level and medication adherence of patients and can be used by nurses in
      addition to medication.

PMID- 30201203
TI  - Living a tormented life: Caregivers' experiences of caring for a child with
      autism in Northeastern Thailand.
AB  - Caring for children with autism spectrum disorder (ASD) can be a demanding
      challenge to caregivers. The aim of this study was to learn what caring for
      children with ASD means to caregivers who live in rural Thailand. A hermeneutic
      phenomenological approach was used to analyze narrative data from interviews of
      five caregivers. Three themes emerged: (a) being sensitive to the word autism,
      (b) being trapped in a tunnel of distress, and (c) being the universe for the
      child. Healthcare professionals need to be sensitive to the caregivers' cultural
      customs in order to meet their expectations in a respectful way.

PMID- 30201204
TI  - Beliefs about prognosis and outcomes for people with mental disorders: A cross
      cultural study of Bachelor of Nursing students from the US and China.
AB  - The purpose of this study is to examine and compare the US and Chinese Bachelor
      of Nursing students' beliefs about prognosis and long-term outcomes for people
      with depression and schizophrenia following interventions. A total of 310 nursing
      students in the US (n = 152) and China (n = 158) completed a survey questionnaire
      between April 2016 and April 2017. Overall, the Chinese students rated prognosis
      and outcomes more negatively than did the US students. The main finding suggests
      the need for cultural-specific pedagogical considerations to be given to mental
      health education in undergraduate nursing curricula in the US and China.

PMID- 30201205
TI  - Mental health literacy levels.
AB  - Globally, mental disorders affect 25% of the society. This discursive paper aims
      to illustrate the mental health literacy levels in the public. Mental health
      literacy (MHL) is the understanding of mental health conditions, which helps in
      their prevention, recognition and treatment. Unfortunately, the public has
      minimal understanding of mental disorders, leading to poor recognition and delay
      in treatment. There is a need to conduct good quality research to assess the MHL
      levels among public and tailor interventions to enhance MHL among the public.
      This will ensure early detection of mental disorders, leading to early recovery
      and greater quality of life among the society. Nurses have a great role to play
      in leading these public educations, and enhancing a healthy and happy nation.

PMID- 30201207
TI  - Understanding the meaning of seeking healthcare for Operation Enduring Freedom
      (OEF) and Operation Iraqi Freedom (OIF) male veterans: An interpretive
      phenomenological study.

PMID- 30201206
TI  - Implementing seclusion in forensic mental health care: A qualitative study of
      staff decision making.
AB  - Forensic mental health nursing is a complex role and there is a tension between
      maintaining safety and promoting a therapeutic and patient centred approach. The
      use of restrictive practises such as seclusion is an issue. Two focus groups with
      registered nurses exploring attitudes and factors used in decision-making about
      seclusion use were analysed using interpretive description. Participants
      described the need to reduce the use of seclusion and the problematic nature of
      its utility as an ongoing intervention in contemporary mental healthcare. It was
      clear that there were complexities and competing variables involved in the
      decision-making process.

PMID- 30201208
TI  - Prevalence and predictors of PTSD and depression among adolescent victims of the
      Summer 2016 tornado in Yancheng City.
AB  - The aim of this study was to investigate the prevalence rate of probable
      posttraumatic stress disorder (PTSD) and depression in the adolescents who
      experienced the 2016 Yancheng tornado 3 months ago, as well as to analyze the
      related risk factors. A total of 247 tornado adolescent survivors were recruited
      to complete child PTSD symptom scale and Center for Epidemiologic Studies
      Depression Scale for Children. Results showed that 57.5% and 58.7% of the
      participants reported suspected symptoms of PTSD and depression respectively.
      PTSD is highly comorbid with depression. Risk factors of these two disorders were
      age and tornado exposure. Finally, the implications of intervention and
      prevention of mental health problems among adolescents who experienced tornado
      were discussed.

PMID- 30201209
TI  - [Idiopathic lipoatrophic panniculitis in an adult treated with hydroxychloroquine
      and adipocyte grafting].
AB  - BACKGROUND: Idiopathic lipoatrophic panniculitis is a rare disease. Various terms
      are used in the literature to describe similar entities: annular lipoatrophy of
      the ankles, lipophagic panniculitis and lipoatrophic panniculitis. In any event,
      it consists of an inflammatory process progressing to necrosis of the fatty
      tissue. PATIENTS AND METHODS: Herein we report the case of a 37-year-old woman
      presenting characteristic signs: erythematous, annular, symmetrical, painful,
      inflammatory lesions of the lower extremities, progressing to areas of atrophy
      with an indurated inflammatory periphery. Histopathology showed lobular
      panniculitis composed primarily of lymphocytes and macrophages. The etiological
      investigations ruled out all other causes of lobular panniculitis. The patient
      was successfully treated with hydroxychloroquine 400mg/day for 1 year and she
      subsequently underwent fat grafting on the secondary lesions. DISCUSSION: Our
      literature review identified 23 reported cases of idiopathic lipoatrophic
      panniculitis since 2006, including 10 cases of annular ankle lipoatrophy. The
      most commonly used treatments are corticosteroids, hydroxychloroquine and
      methotrexate, with good efficacy being seen on the inflammatory phase. This
      disease seems a good indication for fat grafting to limit aesthetic sequelae.
      CONCLUSION: Lipoatrophic panniculitis, a rare disease, results in significant
      aesthetic sequelae which may be limited by early treatment initiation. The
      benefit-risk ratio of hydroxychloroquine suggests its value as first-line therapy
      in this pathology. Our case also demonstrates the value of filling of the
      secondary atrophy by fat grafting after the inflammatory period has ended.

PMID- 30201210
TI  - The combination of the opioid glycopeptide MMP-2200 and a NMDA receptor
      antagonist reduced l-DOPA-induced dyskinesia and MMP-2200 by itself reduced
      dopamine receptor 2-like agonist-induced dyskinesia.
AB  - Dopamine (DA)-replacement therapy utilizing l-DOPA is the gold standard
      symptomatic treatment for Parkinson's disease (PD). A critical complication of
      this therapy is the development of l-DOPA-induced dyskinesia (LID). The
      endogenous opioid peptides, including enkephalins and dynorphin, are co
      transmitters of dopaminergic, GABAergic, and glutamatergic transmission in the
      direct and indirect striatal output pathways disrupted in PD, and alterations in
      expression levels of these peptides and their precursors have been implicated in
      LID genesis and expression. We have previously shown that the opioid glycopeptide
      drug MMP-2200 (a.k.a. Lactomorphin), a glycosylated derivative of Leu-enkephalin
      mediates potent behavioral effects in two rodent models of striatal DA depletion.
      In this study, the mixed mu-delta agonist MMP-2200 was investigated in standard
      preclinical rodent models of PD and of LID to evaluate its effects on abnormal
      involuntary movements (AIMs). MMP-2200 showed antiparkinsonian activity, while
      increasing l-DOPA-induced limb, axial, and oral (LAO) AIMs by ~10%, and had no
      effect on dopamine receptor 1 (D1R)-induced LAO AIMs. In contrast, it markedly
      reduced dopamine receptor 2 (D2R)-like-induced LAO AIMs. The locomotor AIMs were
      reduced by MMP-2200 in all three conditions. The N-methyl-d-aspartate receptor
      (NMDAR) antagonist MK-801 has previously been shown to be anti-dyskinetic, but
      only at doses that induce parkinsonism. When MMP-2200 was co-administered with MK
      801, MK-801-induced pro-parkinsonian activity was suppressed, while a robust anti
      dyskinetic effect remained. In summary, the opioid glycopeptide MMP-2200 reduced
      AIMs induced by a D2R-like agonist, and MMP-2200 modified the effect of MK-801 to
      result in a potent reduction of l-DOPA-induced AIMs without induction of
      parkinsonism.

PMID- 30201211
TI  - Reduced cortical serotonin 5-HT2A receptor binding and glutamate activity in high
      compulsive drinker rats.
AB  - Serotonin2A receptors and glutamate signaling have been implicated in the
      pathophysiology and treatment of compulsive spectrum disorders. Schedule-Induced
      Polydipsia (SIP), characterized by excessive drinking under intermittent food
      reinforcement schedules, is a valid model for studying the compulsive phenotype
      in rats. We explored the expression, function, and neurochemistry of 5-HT2A
      receptors in the frontal cortex (FC) of rats with individual differences to
      compulsivity. Rats were selected for high (HD) versus low (LD) drinking on SIP.
      First, we measured 5-HT2A, 5-HT1A, and mGlu2/3 receptors and serotonin
      transporter binding in different brain regions. Second, we assessed the effect of
      microinfusion into the medial prefrontal cortex (mPFC) of the 5-HT2A/C receptor
      agonist DOI, the mGlu2/3 agonist LY379268, and the combination of DOI with the 5
      HT2A receptor antagonist M100907 and the 5-HT2C receptor antagonist SB242084.
      Finally, we measured the serotonin and glutamate efflux in mPFC in basal
      condition and after DOI local application. The compulsive HD rats showed a
      specific reduction of 5-HT2A receptor binding in FC compared to LD rats. The
      highest dose of DOI reduced compulsive drinking in HD rats on SIP, whereas
      LY379268 did not induce any significant effect. The 5-HT2A receptor antagonist
      M100907 reversed the DOI induced reduction on compulsive drinking in HD rats
      while blocking the 5-HT2C receptor did not affect SIP. Compulsive HD rats showed
      increased serotonin and decreased glutamate efflux in basal conditions that were
      modified by the DOI application. These findings indicate that reduced 5-HT2A
      receptor binding and glutamate neurochemical mechanisms may underlie compulsive
      behavior vulnerability.

PMID- 30201212
TI  - Blood-brain barrier integrity in a mouse model of Alzheimer's disease with or
      without acute 3D6 immunotherapy.
AB  - The blood-brain barrier (BBB) is suggested to be compromised in Alzheimer's
      disease (AD). The concomitant presence of vascular amyloid beta (Abeta)
      pathology, so called cerebral amyloid angiopathy (CAA), also predisposes
      impairment of vessel integrity. Additionally, immunotherapy against Abeta may
      lead to further damage of the BBB. To what extent this affects the BBB passage of
      molecules is debated. The current study aimed to investigate BBB integrity to
      large molecules in transgenic mice displaying abundant Abeta pathology and age
      matched wild type animals, with or without acute anti-Abeta antibody treatment.
      Animals were administered a single i.v. injection of PBS or 3D6 (10 mg/kg), i.e.
      the murine version of the clinically investigated Abeta antibody bapineuzumab,
      supplemented with [125I]3D6. Three days post injections, a 4 kDa FITC and a 150
      kDa Antonia Red dextran were administered i.v. to all animals. After termination,
      fluorescent detection in brain and serum was used for the calculation of dextran
      brain-to-blood concentration ratios. Further characterization of antibody fate
      and the presence of CAA were investigated using radioactivity measurements and
      Congo red staining. BBB passage of large molecules was equally low in wild type
      and transgenic mice, suggesting an intact BBB despite Abeta pathology. Neither
      was the BBB integrity affected by acute 3D6 treatment. However, CAA was confirmed
      in the transgenes and local antibody accumulations were observed in the brain,
      indicating CAA-antibody interactions. The current study shows that independently
      of Abeta pathology or acute 3D6 treatment, the BBB is intact, without extensive
      permeability to large molecules, including the 3D6 antibody.

PMID- 30201213
TI  - Evaluation of a Preoperative Optimization Protocol for Primary Hip and Knee
      Arthroplasty Patients.
AB  - BACKGROUND: Preoperative optimization of risk factors has been suggested as a
      strategy to improve the value of total joint arthroplasty (TJA) care. We assessed
      the implementation of a TJA preoperative optimization protocol and its impact on
      length of hospital stay, discharge destination, 90-day readmissions, and hospital
      direct variable costs. METHODS: This retrospective cohort study included adults
      undergoing primary elective TJA from 07/2015-09/2016 at an urban tertiary care
      hospital. Post-implementation patients were preoperatively screened for 19 risk
      factors; results and recommended interventions were reported to surgeons, who had
      the option to postpone or continue surgery as scheduled. Metrics from hospital
      administrative databases were compared between post-implementation (02/2016
      09/2016) and pre-implementation cohorts (07/2015-11/2015). RESULTS: The 314 post
      implementation patients were slightly younger compared to the 351 pre
      implementation patients (64.2 years vs 65.8 years, P = .02) and a higher
      percentage of patients had diabetes (18% vs 5.1%, P < .001). Of the 98% of post
      implementation patients screened, 74% had at least 1 risk factor identified.
      Obstructive sleep apnea was the most common risk factor (52%), followed by
      depression (22%) and obesity (body mass index > 40 kg/m2 or 35-40 kg/m2 with
      comorbidities) (13%). Forty-six patients (20%) did not follow through with the
      recommended optimization before undergoing elective surgery. The post
      implementation cohort had shorter average length of hospital stay (1.9 days vs
      2.2 days, P < .001) and lower average total direct variable costs excluding
      implants ($5409 vs $5852, P < .001). There was no difference in patients
      discharged home (90% vs 89%, P = .53) or 90-day readmissions (4.1% vs 4.3%, P =
      .93). CONCLUSION: In our experience, the majority of elective TJA patients have
      modifiable risk factors, indicating opportunity for preoperative intervention.
      Our evidence-based preoperative optimization program resulted in higher value
      care, demonstrated by similar outcomes with lower resource utilization.

PMID- 30201215
TI  - Cross-Sectional Patient-Reported Outcome Measuring of Health-Related Quality of
      Life With Establishment of Cancer- and Treatment-Specific Functional and Symptom
      Scales in Patients With Penile Cancer.
AB  - BACKGROUND: In the field of uro-oncology, the assessment of quality of life (QoL)
      is considered an integral part of clinical research. Because of the rarity of
      penile cancer, there is currently no cancer-specific questionnaire module
      available to assess the tumor-specific loss of function and symptoms in terms of
      influencing QoL. The aim of the study was to apply a validated questionnaire
      (European Organization for Research and Treatment of Cancer [EORTC] QLQ-C30) in a
      population of patients diagnosed with penile cancer and to compare these results
      to reference data of the general population. We also developed a new unvalidated
      questionnaire (Quality of Life Questionnaire-Penile Cancer-Rostock, HRO-PE29) in
      this population to promote QoL research in the field of uro-oncology. PATIENTS
      AND METHODS: Cross-sectional evaluation of patients with penile cancer after
      local surgical treatment (n = 76) was performed using EORTC QLQ-C30 and HRO-PE29.
      The QLQ-C30 provides information on QoL, functional scales, symptom scales, and 6
      individual items (inappetence, insomnia, dyspnea, constipation, diarrhea,
      financial difficulties). Cancer-specific functional and symptom scales (HRO-PE29)
      were then established for use in different disease states and forms of treatment.
      These provide information on QoL as well as on cancer-specific function and
      symptom scores. RESULTS: The global QoL score was 54, which corresponds to an
      average QoL (score 0-100) and was well below the age-standardized average for
      German patients. For the general function scores, the following mean values were
      determined: physical (x- = 73), social (x- = 61), emotional (x- = 60), cognitive
      functioning (x- = 69), and role function (x- = 63). With regard to the general
      symptom scores and the individual items, the following values were found: fatigue
      (x- = 35), nausea (x- = 6), pain (x- = 27), dyspnea (x- = 23), insomnia (x- =
      41), loss of appetite (x- = 25), constipation (x- = 19), diarrhea (x- = 10), and
      financial difficulties (x- = 25). The following mean values were found for the
      cancer-specific functional scores: voiding (x- = 77), sexuality (x- = 69,
      function and pleasure), body image (x- = 64), lymphedema (x- = 75), future
      prospects (x- = 72), and adverse effects of systemic treatment (x- = 73).
      CONCLUSION: Defects of the external genitalia have implications for identity,
      personality, and interpersonal relationships. The mental stress of these patients
      results from the diagnosis of cancer as well as the partly mutilating treatment.
      Reconstructive surgery in penile cancer patients promises to maintain sexual and
      micturition function and thus improve QoL. Cancer-specific functional losses can
      be sufficiently named and their influence on QoL determined.

PMID- 30201216
TI  - Discovery.

PMID- 30201214
TI  - Functional characterization of 40 CYP2B6 allelic variants by assessing efavirenz
      8-hydroxylation.
AB  - Genetic variations within cytochrome P450 2B6 (CYP2B6) contribute to inter
      individual variation in the metabolism of clinically important drugs, including
      cyclophosphamide, bupropion, methadone and efavirenz (EFZ). In this study, we
      performed an in vitro analysis of 40 CYP2B6 allelic variant proteins including
      seven novel variants identified in 1070 Japanese individuals. Wild-type and 39
      variant proteins were heterologously expressed in 293FT cells to estimate the
      kinetic parameters (Km, Vmax, and CLint) of EFZ 8-hydroxylation and 7-ethoxy-4
      trifluoromethylcoumarin (7-ETC) O-deethylation activities. The concentrations of
      CYP2B6 variant holo-enzymes were measured by using carbon monoxide (CO)-reduced
      difference spectroscopy, and the wild-type and 28 variants showed a peak at 450
      nm. The kinetic parameters were measured for the wild-type and 24 variant
      proteins. The values for the remaining 15 variants could not be determined
      because the enzymatic activity was not detected at the highest substrate
      concentration used. Compared to wild-type, six variants showed significantly
      decreased EFZ 8-hydroxylation CLint values, while these values were significantly
      increased in another six variants, including CYP2B6.6. Although 7-ETC O
      deethylation CLint values of CYP2B6 variants did not differ significantly from
      that of CYP2B6.1, the CLint ratios obtained for 7-ETC O-deethylation were highly
      correlated with EFZ 8-hydroxylation. Furthermore, three-dimensional structural
      modeling analysis was performed to elucidate the mechanism of changes in the
      kinetics of CYP2B6 variants. Our findings could provide evidence of the specific
      metabolic activities of the CYP2B6 proteins encoded by these variant alleles.

PMID- 30201217
TI  - Comparison of radiographic and clinical outcomes of revision reverse total
      shoulder arthroplasty with structural versus nonstructural bone graft.
AB  - BACKGROUND: Revision shoulder arthroplasty in the setting of glenoid bone loss
      poses substantial surgical challenges. This study's purpose was to compare
      radiographic and clinical results of patients requiring structural iliac crest
      bone autograft (ICBA) for severe bone loss versus patients with less severe bone
      loss treated with nonstructural bone allograft (NSBA) in the setting of revision
      reverse total shoulder arthroplasty (RSA). METHODS: A retrospective cohort of 30
      patients (70% of the 43 patients who met the inclusion criteria) undergoing
      revision RSA with ICBA (n = 15) or NSBA (n = 15) between 2007 and 2015 were
      analyzed at a minimum 2-year follow-up. Radiographic assessment included bone
      graft integration, bone graft resorption, glenosphere tilt, glenosphere version,
      and the presence of scapular notching. Clinical assessment included active range
      of motion, Penn Shoulder Score, Veterans RAND 12-item health survey, and need for
      revision surgery. RESULTS: No radiographic difference was found between the ICBA
      and NSBA groups with regard to implant position, graft integration, scapular
      notching, implant shift, or failure of fixation (P > .05). Of 15 patients with
      ICBA, 14 (93%) had at least partial integration of the bone graft. Some degree of
      resorption of the bone graft was noted in 6 of 15 patients (40%). There was no
      significant difference in postoperative active range of motion, Penn Shoulder
      Score, or Veterans RAND 12-item health survey score (P > .05 for all
      comparisons). One patient in the ICBA group underwent revision surgery for
      glenoid baseplate failure. CONCLUSION: Revision RSA with glenoid bone grafting
      resulted in good clinical and radiographic outcomes at short-term follow-up.
      Patients requiring structural ICBA were not at increased risk of component
      failure, radiographic or clinical complications, or inferior clinical outcomes.

PMID- 30201218
TI  - Effects of early life stress on biochemical indicators of the dopaminergic
      system: A 3 level meta-analysis of rodent studies.
AB  - Adverse early life events are a well-established risk factor for the
      precipitation of behavioral disorders characterized by anomalies in the
      dopaminergic system, such as schizophrenia and addiction. The correlation between
      early life conditions and the dopaminergic system has been causally investigated
      in more than 90 rodent publications. Here, we tested the validity of the
      hypothesis that early life stress (ELS) alters dopamine signaling by performing
      an extensive 3-level mixed effect meta-analysis. We included several ELS models
      and biochemical indicators of the dopaminergic system in a variety of brain
      areas, for a total of 1009 comparisons. Contrary to our expectations, only a few
      comparisons displayed a significant effect. Specifically, the striatal area was
      the most vulnerable, displaying decreased dopamine precursor and increased
      metabolites after ELS. To make all data openly accessible, we created MaDEapp
      (https://osf.io/w25m4/), a tool to explore data of the meta-analysis with the
      intent to guide future (pre)clinical research and allow power calculations. All
      in all, ELS induces a few yet robust changes on biochemical indicators of the
      dopaminergic system.

PMID- 30201220
TI  - Adolescence as a neurobiological critical period for the development of higher
      order cognition.
AB  - The transition from adolescence to adulthood is characterized by improvements in
      higher-order cognitive abilities and corresponding refinements of the structure
      and function of the brain regions that support them. Whereas the neurobiological
      mechanisms that govern early development of sensory systems are well-understood,
      the mechanisms that drive developmental plasticity of association cortices, such
      as prefrontal cortex (PFC), during adolescence remain to be explained. In this
      review, we synthesize neurodevelopmental findings at the cellular, circuit, and
      systems levels in PFC and evaluate them through the lens of established critical
      period (CP) mechanisms that guide early sensory development. We find remarkable
      correspondence between these neurodevelopmental processes and the mechanisms
      driving CP plasticity, supporting the hypothesis that adolescent development is
      driven by CP mechanisms that guide the rapid development of neurobiology and
      cognitive ability during adolescence and their subsequent stability in adulthood.
      Critically, understanding adolescence as a CP not only provides a mechanism for
      normative adolescent development, it provides a framework for understanding the
      role of experience and neurobiology in the emergence of psychopathology that
      occurs during this developmental period.

PMID- 30201221
TI  - "Same same or different?" A review of reviews of person-centered and patient
      centered care.
AB  - OBJECTIVE: To provide a synthesis of already synthesized literature on person
      centered care and patient-centered care in order to identify similarities and
      differences between the two concepts. METHODS: A synthesis of reviews was
      conducted to locate synthesized literature published between January 2000 and
      March 2017. A total of 21 articles deemed relevant to this overview were
      synthesized using a thematic analysis. RESULTS: The analysis resulted in nine
      themes present in person-centered as well as in patient-centered care: (1)
      empathy, (2), respect (3), engagement, (4), relationship, (5) communication, (6)
      shared decision-making, (7) holistic focus, (8), individualized focus, and (9)
      coordinated care. The analysis also revealed that the goal of person-centered
      care is a meaningful life while the goal of patient-centered care is a functional
      life. CONCLUSIONS: While there are a number of similarities between the two
      concepts, the goals for person-centered and patient-centered care differ. The
      similarities are at the surface and there are important differences when the
      concepts are regarded in light of their different goals. PRACTICE IMPLICATIONS:
      Clarification of the concepts may assist practitioners to develop the relevant
      aspects of care. Person-centered care broadens and extends the perspective of
      patient-centered care by considering the whole life of the patient.

PMID- 30201222
TI  - Agreement of clinical tests for the diagnosis of peripheral arterial disease.
AB  - AIM: The aim of this study was to compare different screening modalities in the
      detection of PAD in a primary care setting. METHODS: Fifty participants living
      with Type 2 diabetes were recruited. Pulse palpation, waveform analysis, ankle
      brachial pressure index, absolute toe pressure, toe brachial pressure index and
      transcutaneous oxygen pressure were compared in the detection of peripheral
      arterial disease. One hundred limbs were included for analysis. RESULTS: This
      study showed different results in peripheral arterial disease screening tests in
      the same group of participants. The highest percentage of participants who had
      PAD was for the Doppler Waveform (93.0%). This was followed by TBPI (72.0%), ABPI
      (57.0%), ATP (35.0%), TCPO (30.0%) and pulse palpation (23.0%). The difference
      between these percentages is significant (p<0.0005). The magnitude of the effect
      size is medium/moderate (Cramer's V=0.498). CONCLUSION: This study demonstrates
      that inconsistencies exist between the agreement of the 6 different modalities
      used to detect PAD. These findings should create an awareness amongst clinicians
      when interpreting results of these tests. The authors advocate for urgent, more
      robust studies utilizing a gold standard modality for the diagnosis of PAD in
      order to provide evidence regarding which screening modalities would yield the
      most valid results.

PMID- 30201223
TI  - Prophylactic Cranial Irradiation Versus Surveillance: Physician Bias and Patient
      centered Decision-making.
AB  - An original work in this month's issue of Clinical Lung Cancer highlights the
      role of physician bias in the decision to recommend prophylactic cranial
      irradiation (PCI) to patients with small-cell lung cancer, and presents a patient
      decision aid to facilitate discussion. After decades of clinical trials, we've
      learned that PCI can significantly decrease the risk of brain metastases and
      possibly improve survival. However, PCI is also associated with negative impacts
      on cognition and quality of life. At present, there is no consensus on how to
      balance these risks and benefits. Understanding and exploring these issues in a
      structured fashion offers an opportunity to return decision-making to patients,
      incorporating their values and priorities.

PMID- 30201224
TI  - Nerve ultrasound to prevent and treat iatrogenic sural nerve injury.

PMID- 30201225
TI  - Vitamin D supplementation may improve back pain disability in vitamin D deficient
      and overweight or obese adults.
AB  - Back pain is currently the greatest cause of disability worldwide, and there are
      very limited therapeutic options available. Vitamin D deficiency and obesity are
      both risk factors for back pain. The few randomised controlled trials examining
      the effects of vitamin D supplementation on back pain have methodological
      limitations and largely include non-vitamin D deficient participants. Thus, the
      aim of this study was to determine whether vitamin D supplementation improves
      back pain symptoms in vitamin D deficient and overweight or obese, otherwise
      healthy adults. Sixty-five overweight or obese adults (BMI >= 25 kg/m2) with
      vitamin D deficiency (25-hydroxyvitamin D [25(OH)D] concentrations <=50 nmol/L)
      were randomised to a bolus oral dose of 100,000 IU followed by 4000 IU
      cholecalciferol/day or matching placebo for 16 weeks. We measured 25(OH)D
      concentrations (chemiluminescent immunoassays) and self-reported back pain
      (Chronic Pain Grade Questionnaire) before and after the intervention. Lifestyle
      habits including sun exposure, physical activity, and diet were collected using
      questionnaires. Fifty-four participants completed the study, of which 49 had
      complete data for back pain and were included in the present analyses (31 M/18 F;
      mean +/- SD age: 31.8 +/- 8.9 years; BMI: 31.1 +/- 4.5 kg/m2). After the 16-week
      intervention, 25(OH)D levels increased significantly with vitamin D
      supplementation compared with placebo (55.7 +/- 20.9 versus 3.9 +/- 14.4 nmol/L,
      respectively, p < 0.001). There were no significant differences between vitamin D
      and placebo groups in change in back pain intensity or disability scores (all p >
      0.05). However, in those with 25(OH)D concentrations <30 nmol/L at baseline (n =
      20), there was a significantly greater reduction in back pain disability scores
      in the vitamin D group compared with placebo, after adjusting for important
      covariates known to affect vitamin D status and/or back pain (b [95%CI] = -11.6 [
      22.4, -0.8], p = 0.04). Our findings suggest that vitamin D supplementation in
      overweight or obese and markedly vitamin D deficient adults (25(OH)D <30 nmol/L)
      may improve back pain disability. Although treating severe vitamin D deficiency
      is recommended for optimising bone health, this study suggests it may also
      improve back pain. Hence, testing for vitamin D deficiency in those with back
      pain who are overweight or obese may be warranted.

PMID- 30201219
TI  - The role of inflammation in core features of depression: Insights from paradigms
      using exogenously-induced inflammation.
AB  - A wealth of evidence has implicated inflammation in the development of
      depression. Yet, the heterogeneous nature of depression has impeded efforts to
      understand, prevent, and treat the disease. The purpose of this integrative
      review is to summarize the connections between inflammation and established core
      features of depression that exhibit more homogeneity than the syndrome itself:
      exaggerated reactivity to negative information, altered reward processing,
      decreased cognitive control, and somatic syndrome. For each core feature, we
      first provide a brief overview of its relevance to depression and neurobiological
      underpinnings, and then review evidence investigating a potential role of
      inflammation. We focus primarily on findings from experimental paradigms of
      exogenously-induced inflammation. We conclude that inflammation likely plays a
      role in exaggerated reactivity to negative information, altered reward
      reactivity, and somatic symptoms. There is less evidence supporting an effect of
      inflammation on cognitive control as assessed by standard neuropsychological
      measures. Finally, we discuss implications for future research and
      recommendationsfor how to test the role of inflammation in the pathogenesis of
      heterogeneous psychiatric disorders.

PMID- 30201226
TI  - Serial changes in exercise capacity, quality of life and cardiopulmonary
      responses after pulmonary rehabilitation in patients with chronic obstructive
      pulmonary disease.
AB  - BACKGROUND AND OBJECTIVES: Patients with chronic obstructive pulmonary disease
      (COPD) often have poor health-related quality of life (HRQL), exercise capacity
      and cardiopulmonary function. Pulmonary rehabilitation (PR) is beneficial to
      improve exercise capacity and HRQL. However, series changes of these parameters
      remain unclear. METHODS: Forty-three subjects participated in a 3-months PR
      program. Subjects were evaluated at baseline and at 8, 16, and 24 sessions after
      PR. RESULTS: After 8 sessions, there were significant improvements in the SGRQ
      symptom domain, exertional dyspnea, and oxygen pulse (all p < 0.05). Maximal VO2,
      SGRQ-activity and SGRQ-impact domains, and respiratory muscle strength were
      significantly improved after 16 and 24 sessions (all p < 0.05). CONCLUSIONS:
      Eight sessions of exercise training lead to improvement of symptoms and
      exertional dyspnea. 16 to 24 sessions result in further improvement. We suggest
      patients receive 16 to 24 sessions of PR.

PMID- 30201228
TI  - The impact of the number of harvested central lymph nodes on the lymph node
      ratio.
AB  - OBJECTIVE: The purpose of this study was to analyze the impact of lymph node
      harvest on the lymph node ratio (LNR). METHODS: We retrospectively reviewed 106
      patients diagnosed preoperatively with PTMC (papillary thyroid microcarcinoma),
      no evidence of central or lateral neck nodal metastasis, and who underwent a
      total thyroidectomy and bilateral central lymph node neck dissection (CND).
      RESULTS: The median number of retrieved lymph nodes in the central compartments
      was 7+/-6.59 (range: 1-42). The mean number of metastatic lymph nodes in the
      central compartments on pathology was 1.1+/-1.79 (range: 0-7). The high node
      volume group (>7) had a significantly higher rate of central lymph node (CLN)
      metastasis than the low node volume group (<=7) in the final pathologic report
      (p<0.001). With the linear regression method, the number of CLN metastasis
      increased as the number of retrieved lymph nodes increased (correlation
      coefficient=0.286, p=0.003). The multivariate analysis confirmed the number of
      retrieved lymph nodes in the central compartments was a risk factor for high LNR
      (p=0.008, odds ratio 3.737). The rates of vocal fold palsy and hypoparathyroidism
      did not differ according to the number of retrieved lymph nodes. CONCLUSION: The
      lymph node ratio in the final pathologic report is larger when a greater number
      of lymph nodes are retrieved during the central compartment neck dissection.

PMID- 30201227
TI  - Vibrant Soundbridge implantation via a retrofacial approach in a patient with
      congenital aural atresia.
AB  - OBJECTIVE: A method of Vibrant Soundbridge (VSB) placement to the round window
      (RW) via the retrofacial approach with preoperative evaluation of the
      relationship between the facial nerve (FN) and RW by 3D-CT reconstruction was
      proposed for the treatment of congenital aural atresia (CAA) patient. METHODS: A
      fenestration to the mesotympanum was made mastoid portion of the FN. During the
      approach, part of the stapedial muscle was encountered and removed. The RW niche
      was identified, and the floating mass transducer was placed from an inferior
      approach into the RW niche. RESULTS: There were no intra-operative or post
      operative surgical complications. CONCLUSION: The VSB placement to the RW via the
      retrofacial approach with partial removal of the stapedial muscle can be feasible
      alternative in CAA cases associated with an anteriorly and laterally positioned
      aberrant FN. Preoperative assessment using 3D CT may facilitate in assessing the
      feasibility of the approach and implantation of VSB.

PMID- 30201229
TI  - Root bark of Discaria americana attenuates pain: A pharmacological evidence of
      interaction with opioidergic system and TRP/ASIC channels.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Discaria americana (Rhamnaceae) root bark
      infusion have been used in traditional medicine as antipyretic, tonic,
      ameliorative of stomach and skin diseases and diabetes. This study was designed
      to investigate whether the methanolic extract of the root bark of Discaria
      americana (MEDa) exhibits antinociceptive effects in mice. Furthermore, it was
      investigated the involvement of the opioidergic system in MEDa mechanism of
      action as well the interactions with TRP/ASIC channels in its effect. MATERIALS
      AND METHODS: The antinociceptive effect of intra-gastric gavage (i.g.) of MEDa
      (0.3-300 mg/kg) was evaluated in mice subjected to acute chemical (acetic-acid,
      formalin, glutamate, capsaicin, cinnamaldehyde, and acidified saline) or thermal
      (hot plate) tests of pain. The involvement of opioid system was evaluated in the
      formalin test. A nonspecific effect of MEDa was observed by measuring locomotor
      activity and exploratory behavior in open field test. RESULTS: MEDa significantly
      reduced the number of writhing induced by acetic acid and inhibited the
      nociception in the two phases of formalin. These effects were inhibited by
      pretreatment with naloxone. The nociception induced by hot plate and intraplantar
      injection of glutamate, capsaicin, cinnamaldehyde and acidified saline were
      significantly inhibited by MEDa. Only the dose of 300 mg/kg altered the locomotor
      activity. CONCLUSIONS: Our results demonstrated, for the first time, that the
      methanolic extract of the root bark of Discaria americana presents
      antinociceptive effect in chemical and thermal stimuli and its analgesic
      properties can be due activation of the opioidergic system. These results support
      the use of Discaria americana in traditional medicine and demonstrate that this
      plant presents a therapeutic potential for the development of phytomedicines with
      antinociceptive profile.

PMID- 30201230
TI  - In vitro antiplasmodial activity and identification, using tandem LC-MS, of
      alkaloids from Aspidosperma excelsum, a plant used to treat malaria in Amazonia.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Aspidosperma excelsum Benth. (Apocynaceae), a
      native tree in the Brazilian Amazonia, is traditionally used to treat various
      diseases, including malaria. AIM OF STUDY: To investigate the chemical
      constitution, antiplasmodial activity and cytotoxicity of samples obtained from
      A. excelsum trunk bark by different procedures aiming to evaluate their potential
      as an antimalarial phytomedicine. MATERIALS AND METHODS: A hydroethanolic extract
      and alkaloid extracts were prepared and assayed for antiplasmodial activity and
      cytotoxicity against chloroquine-resistant Plasmodium falciparum (W2 strain) and
      HepG2 cells, respectively. Taking into account the known occurrence and
      antimalarial activity of Aspidosperma monoterpene indole alkaloids (MIA), acid
      base extractions were carried out and the fractions were assayed for
      antiplasmodial activity and cytotoxicity. All the samples were analysed by
      hyphenated chromatographic techniques, such as UPLC-DAD-ESI-MS/MS and HRMS (HPLC
      MS MicroTOF), comparing their chemical composition to the literature data.
      RESULTS: The hydroethanolic extract disclosed a moderate in vitro activity
      against chloroquine-resistant Plasmodium falciparum (W2 strain) with IC50 23.68
      +/- 3.08 ug/mL), low cytotoxicity to HepG2 cells (> 250 ug/mL) and good SI (>
      10.56). A total of 20 known monoterpene indole alkaloids were identified, seven
      of which are here firstly described for A. excelsum. Known highly active
      alkaloids, namely demethylaspidospermine, aspidocarpine, and ochrolifuanine are
      present in active alkaloid fractions and might contribute to their observed
      antiplasmodial effect. An alkaloid fraction (Ae-Alk2), obtained directly from
      trunk bark by extraction with dil. aqueous HCl, pointed out for its activity
      (IC50 8.75+/-2.26 ug/mL, CC50 185.14+/-1.97 ug/mL, SI 21.16) and should be
      highlighted as the most promising out of the assayed samples. CONCLUSION: The
      present results represent a preliminary support to the alleged antimalarial use
      of A. excelsum trunk bark and allowed to highlight alkaloid fractions as
      promising phytomedicines.

PMID- 30201231
TI  - Bioactivity of Acanthus mollis - Contribution of benzoxazinoids and
      phenylpropanoids.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Acanthus mollis is a plant native to the
      Mediterranean region, traditionally used as diuretic, anti-inflammatory and
      soothing of the mucous membranes of the digestive and urinary tract and
      externally as healing of wounds and burns, also demonstrating analgesic and anti
      inflammatory activities. However, studies focused on its phytochemical
      composition as well as scientific proof of Acanthus mollis efficacy are scarce.
      AIM OF THE STUDY: The proposed work aims to perform a phytochemical
      characterization and evaluation of the therapeutic potential of Acanthus mollis,
      based on biological properties that support its traditional uses. MATERIAL AND
      METHODS: In this study, an 96% ethanol extract from Acanthus mollis leaves was
      obtained and its phytochemical composition evaluated using High Performance
      Liquid Chromatography with Photodiode Array Detector coupled to Electrospray
      Ionization Mass Spectrometry (HPLC-PDA-ESI/MSn). The chemical structure of the
      compound isolated was elucidated using 1H and 13C Nuclear Magnetic Resonance
      (NMR), 1H-correlation spectroscopy (1H-COSY), heteronuclear single quantum
      correlation (HSQC) and heteronuclear multiple-bond correlation (HMBC). The
      quantification of the constituents was performed using two external standards
      (2,4-dihydroxy-1,4-benzoxazin-3-one and verbascoside). The antioxidant activity
      was determined by the 2,2-diphenyl-1-pycrylhydrazyl (DPPH) assay. Anti
      inflammatory activity was determined measuring the inhibition of nitric oxide
      production by RAW 264.7 macrophages stimulated with the TLR4 agonist
      lipopolysaccharide (LPS) and through lipoxygenase (LOX) inhibition assay. The
      cytotoxicity was screened on two lines (RAW 264.7 and HaCaT) using the resazurin
      assay. RESULTS: Compounds such as verbascoside and its derivatives, as well as
      benzoxazinoids were found as the main constituents. A percentage of 5.58% was
      verified for the 2,4-dihydroxy-1,4-benzoxazin-3-one (DIBOA) derivatives. DIBOA
      was the main compound of the extract. Significant concentrations were also found
      for phenylpropanoids, which constitute about 4.39% of the total compounds
      identified. This extract showed antioxidant capacity against DPPH (IC50 = 40.00
      +/- 1.59 MUg/mL) and superoxide anion (IC50 = 29.42 +/- 1.99 MUg/mL). It also
      evidenced anti-inflammatory potential in RAW 264.7 macrophages, presenting
      capacity for nitric oxide reduction (IC50 = 28.01 MUg/mL). Moreover, in vitro
      studies have shown that this extract was able to inhibit the lipoxygenase, with
      an IC50 of 104.39 +/- 4.95 ug/mL. Importantly, all effective concentrations were
      devoid of cytotoxicity in keratinocytes, thus highlighting the safety of the
      extract for the treatment of skin inflammatory related diseases. Concerning
      macrophages it was also possible to disclose concentrations showing anti
      inflammatory activity and without cytotoxicity (up to 30 ug/mL). The
      benzoxazinoid DIBOA demonstrated a considerable anti-inflammatory activity
      suggesting its important contribution to this activity. CONCLUSIONS: These
      results corroborate the anti-inflammatory properties traditionally attributed to
      this plant. Among the compounds identified in this study, benzoxazinoids
      exhibited a significant anti-inflammatory activity that was never previously
      described. Ethanol seems to be a good option for the extraction of these
      bioactive compounds, since relevant antioxidant/anti-radical and anti
      inflammatory activities were found for this extract.

PMID- 30201232
TI  - Transversus abdominis plane blocks with liposomal bupivacaine after open major
      hepatectomy is associated with reduced early patient-reported pain scores and
      opioid administration.
AB  - BACKGROUND: Opioid overprescription can contribute to suboptimal patient
      outcomes. Surgeon-performed transversus abdominis plane blocks appear to be
      associated with pain reduction. We compared the analgesic efficacy of surgeon
      performed transversus abdominis plane blocks for major hepatectomy with or
      without concurrent neuraxial analgesia. METHODS: We performed a single
      institution review, assessing surgeon-performed transversus abdominis plane
      blocks for major hepatectomy during 2013-2016. The primary outcome was patient
      reported pain (11-point numeric pain-rating scale) and the secondary outcome was
      opioid consumption. Independent factors predictive of pain control were
      identified using logistic regression and reported as odds ratios with 95%
      confidence intervals. RESULTS: A total of 232 patients with a mean (+/- SD) age
      of 56.5 (+/-13.9) years; 51.7% were female. Operative duration, incision type,
      and American Society of Anesthesiologists score were similar between groups. The
      24-hour pain score was decreased substantially in patients who received a
      transversus abdominis plane block compared with those who did not (3 [2-4] versus
      5 [4-6], P = .001) and this decrease in pain sscore persisted at 48 hours (2 [1
      2] versus 4 [4-5], P = .001). In patients who received a transversus abdominis
      plane block, there were decreasess in consumption of oral morphine equivalents at
      24 hours (322 [+/- 18] versus 183 [+/- 15], P = .0001) and 48 hours (100 [+/- 11]
      versus 33 [+/- 9.4], P = .03) compared with those without transversus abdominis
      plane block respectively. CONCLUSION: In patients receiving a transversus
      abdominis plane block, early patient opioid consumption was decreased and
      utilization was predictive for improved pain control. Routine transversus
      abdominis plane block administration should be considered during major
      hepatectomy as a step toward curbing systematic reliance on opioids for pain
      management. A prospective study on the utility of transversus abdominis plane
      block in hepatectomy is warranted.

PMID- 30201233
TI  - Peri-operative allogeneic blood transfusion is associated with poor overall
      survival in advanced epithelial ovarian Cancer; potential impact of patient blood
      management on Cancer outcomes.
AB  - BACKGROUND: Transfusion related immune modulation associated with red blood cell
      (RBC) transfusion is thought to result in decreased cancer survival. Results in
      epithelial ovarian cancer (EOC) have been mixed however most suggest worse
      oncologic outcomes in patients who were transfused at the time of debulking
      surgery. The impact of restrictive transfusion strategies on this patient
      population is currently not known. METHODS: We conducted a retrospective study of
      women with EOC. The study population was divided into two groups based on whether
      they were transfused RBCs during the peri-operative period or not. Clinical
      characteristics and prognosticators were compared between groups. Overall
      survival was compared between groups based on transfusion status and other known
      prognostic factors. Cox proportional hazard modeling was used to examine the
      association between the prognostic factors and the study endpoint. RESULTS: Sixty
      six percent of women were transfused. Transfusion was associated with CA125, the
      use of neoadjuvant chemotherapy (NACT), surgical blood loss, and anemia. The mean
      pre-transfusion Hgb was 7.8 + 0.6 g/dL and 94% had a hemoglobin level greater
      than the transfusion threshold of 7 g/dL. RBC transfusion, suboptimal debulking,
      anemia, and NACT were associated with decreased survival. Only RBC transfusion
      and suboptimal debulking status remained significant in a multivariate model.
      CONCLUSIONS: Peri-operative RBC transfusion compromises survival in ovarian
      cancer supporting the need to minimize the use of transfusion at the time of
      debulking surgery. Adherence to evidence-based transfusion guidelines offers an
      opportunity to reduce transfusion rates in this population with a resulting
      positive influence on survival.

PMID- 30201234
TI  - Goal-directed hemodynamic management in patients undergoing primary debulking
      gynaecological surgery: A matched-controlled precision medicine study.
AB  - BACKGROUND: Usefulness of intraoperative goal-directed hemodynamic management
      (GDHM) for patients without comorbidities is debated. After clinical
      implementation of a pulse contour analysis-guided GDHM protocol, which foresees
      early vasopressor use for recruiting unstressed volume, we conducted a matched
      controlled analysis to explore its impact on the amount of fluids
      intraoperatively administered to patients without comorbidities who underwent
      extended abdominal surgery for ovarian cancer. METHODS: After 1:1 matching
      accounting for body mass index, oncologic disease severity and intraoperative
      blood losses, 22 patients treated according to this GDHM protocol were compared
      to a control group of 22 patients who had been managed according to the clinical
      decision of attending physicians, taken without advanced monitoring. Results are
      displayed as median[interquartile range]. RESULTS: All analyzed patients
      underwent radical hysterectomy, bilateral adnexectomy, bowel resection,
      peritonectomy and extended pelvic/periaortic lymphadenectomy; median length of
      surgery was 517[480-605] min in patients receiving GDHM and 507[480-600] min in
      control group. Intraoperatively, patients undergoing GDHM received less fluids
      (crystalloids 2950[2700-3300] vs. 5150[4700-6000] mL, p < 0.001; colloids 100[50
      200] vs. 750[500-1000] mL, p < 0.001) and showed a trend to more frequent
      vasopressor administration (32 vs 9%, p = 0.13). Greater intraoperative diuresis
      (540[480-620] mL vs. 450[400-500] mL, p = 0.007), lower blood lactates at surgery
      end (1.5[1.1-2] vs. 4.1[3.3-5] mmol/L, p < 0.001), shorter time to bowel function
      recovery (1 [1, 2] vs. 4 [3-5] days, p < 0.001) and hospital discharge (7 [6-8]
      vs 12 [9-16] days, p < 0.0001) were detected in patients receiving GDHM.
      CONCLUSIONS: In high-tumor load gynaecological patients without comorbidities who
      receive radical and prolonged surgery, intraoperative use of this novel GDHM
      protocol helped limit fluids administration with safety.

PMID- 30201236
TI  - A novel electrocardiographic parameter for diagnosis of acute pulmonary embolism:
      RS time: RS time in acute pulmonary embolism.
AB  - OBJECTIVES: Pulmonary embolism (PE) is one of the leading causes of
      cardiovascular mortality worldwide. Electrocardiography (ECG) may provide useful
      information for patients with acute PE. In this study, we aimed to investigate
      the diagnostic value of the QRS duration and RS time in inferolateral leads in
      patients admitted to the emergency department, and pre-diagnosed with acute PE.
      METHODS: We retrospectively enrolled 136 consecutive patients, admitted to the
      emergency department, pre-diagnosed with the clinical suspicion of acute PE, and
      underwent computerized tomographic pulmonary angiography (CTPA) to confirm the PE
      diagnosis. The study subjects were divided into two groups according to the
      presence or absence of PE, and the independent predictors of PE were
      investigated. RESULTS: Sixty-eight patients (50%) had PE. Patients with PE had a
      longer RS time. Among the ECG parameters, only RS time was an independent
      predictor of PE (OR: 1.397, 95% CI: 1.171-1.667; p < 0.001). The ROC curve
      analyses revealed that the cut-off value of RS time for predicting acute PE was
      64.20 ms with a sensitivity of 85.3% and a specificity of 79.4% (AUC: 0.846,
      95%CI: 0.749-0.944; p < 0.001). In the correlation analyses; the RS time was
      correlated with RV end-diastolic diameter (r = 0.422; p < 0.001), RV/left
      ventricle (LV) ratio (r = 0.622; p < 0.001), and systolic pulmonary artery
      pressure (SPAP) (r = 0.508; p < 0.001). CONCLUSION: As a novel ECG parameter, RS
      time could be measured for each patient. A longer RS time can be a very useful
      index for diagnosing acute PE as well as for estimating the RV end-diastolic
      diameter and SPAP.

PMID- 30201235
TI  - Lowly-expressed lncRNA GAS5 facilitates progression of ovarian cancer through
      targeting miR-196-5p and thereby regulating HOXA5.
AB  - PURPOSE: This investigation was aimed at extrapolating whether and how lncRNA
      GAS5, miR-196a-5p and HOXA5 altered progression of ovarian cancer (OA). METHOD:
      Totally 195 pairs of OA tissues and adjacent normal tissues were collected. Also
      si-GAS5, pcDNA-GAS5, miR-196a-5p mimic, miR-196a-5p inhibitor and negative
      control (NC) were, respectively, transfected into OA cells. Besides, dual
      luciferase reporter gene assay was performed to validate the targeted
      relationships between GAS5 and miR-196a-5p, as well as between miR-196a-5p and
      HOXA5. The impacts of GAS5, miR-196a-5p and HOXA5 on viability, proliferation and
      apoptosis of OA cells were appraised via conduction of colony formation assay,
      MTT assay and flow cytometry assay. RESULT: Lower GAS5 expression and higher miR
      196a-5p expression were associated with larger tumor size (>=5 cm) and more
      advanced FIGO stage (III-IV) of OA patients (P < 0.05). Transfection of si-GAS5,
      miR-196a-5p mimic or si-HOXA5 conferred OA cells with stronger viability, faster
      proliferation and smaller percentage of apoptosis (P < 0.05). After injecting
      mice models with si-GAS5, miR-196a-5p mimic or si-HOXA5, a larger tumor size was
      also observed within the rats (P < 0.05). GAS5 was indicated to directly target
      miR-196a-5p and modify its expression, and the targeted relationship also seemed
      to exist between miR-196a-5p and HOXA5 (P < 0.05). The HOXA5 was found to reverse
      the effects imposed by miR-196a-5p on viability, proliferation and apoptosis of
      OA cells (P < 0.05). CONCLUSION: LncRNA GAS5 depressed OA development by
      targeting miR-196a-5p and thereby down-regulating HOXA5 expression, providing
      substance for developing lncRNA-based strategies to treat OA.

PMID- 30201237
TI  - Comparing the analgesic efficacy of morphine plus ketamine versus morphine plus
      placebo in patients with acute renal colic: A double-blinded randomized
      controlled trial.
AB  - OBJECTIVES: Renal colic (RC) is a common cause for emergency department visits.
      This study was conducted to compare the analgesic efficacy of morphine plus
      ketamine (MK) versus morphine plus placebo (MP) in patients with acute renal
      colic. METHOD: Using a single center, double-blind, two-arm, parallel-group,
      randomized controlled trial, 200 patients were equally and randomly divided to
      receive 0.1 mg/kg morphine plus normal saline and 0.1 mg/kg morphine plus 0.2
      mg/kg ketamine. The severity of renal colic was assessed by VAS at baseline, 20
      and 40 min after drug injection. The number of adverse events also was recorded.
      RESULTS: Totally, 200 patients completed the study. Mean age of the patients was
      35.60 +/- 8.17 years. The patients were mostly men (68.5%). The severity of pain
      between the groups was not significantly different at baseline. Both groups
      showing a significant reduction in VAS scores across the three time points. The
      main effect comparing the two types of intervention was significant (F = 12.95, p
      = 0.000), suggesting a significant reduction in pain severity of patients in the
      MK group. The number of patients who suffered from vomiting was significantly
      higher in MP group than that of MK group (13 and 3, respectively (P = 0.009)).
      However, the risk of dizziness in the MK group was >2 times higher than MP group
      (relative risk: 2.282, 95% CI: 1.030-5.003, P = 0.039). The number of patients
      who needed rescue analgesia was significantly lower in the MK group (OR, 0.43
      (0.22-0.83)). CONCLUSION: Adding 0.2 mg/kg ketamine to 0.1 mg/kg morphine can
      reduce the renal colic pain, nausea and vomiting more than morphine alone;
      however, it was associated with higher number of patients with dizziness.

PMID- 30201238
TI  - Ambulance transport to the emergency department: A patient-selected signal of
      acuity and its effect on resource provision.
AB  - OBJECTIVE: To determine whether ambulance arrival to the emergency department has
      remained an unidentified signal of perceived medical acuity. Informed by economic
      signaling theory, does arrival via ambulance affect resource utilization given
      varying levels of patient acuity? METHODS: The analysis examined a nationally
      representative sample of de-identified emergency department patient encounters
      from 2011 to 2015, gathered from the National Hospital Ambulatory Medical Care
      Survey (NHAMCS). Multivariate logistic regression analysis was employed using
      regional and time-fixed effects. The provision of twenty diagnostic and imaging
      services was analyzed. Patient encounters were also categorized into five acuity
      levels. RESULTS: Drawing from the NHAMCS dataset, 98,888 emergency department
      records were analyzed, weighted to represent 504.5 million estimated emergency
      department patient encounters. Findings suggest that patients transported to the
      hospital via ambulance are more likely than those who arrive by other means to
      receive 19 of the 20 analyzed diagnostic testing and imaging services.
      Furthermore, when analyzed by acuity-level, the disparity of service provision is
      the greatest among low-acuity patients, where medical complaints are argued to be
      the most subjective. CONCLUSIONS: The results are consistent with the notion that
      emergency department medical providers readily accept ambulance transport as a
      valid signal of patient acuity, regardless of true acuity level. Consequently,
      patients transported to the hospital via ambulance may be receiving a
      disproportionate amount of medical resources in an increasingly cost-conscious
      environment.

PMID- 30201239
TI  - Emergency physician utilization of transvaginal ultrasound after initiation of
      revised sterilization protocol.

PMID- 30201240
TI  - Novel and Emerging Therapeutics for Primary Prevention of Cardiovascular Disease.
AB  - Cardiovascular disease is responsible for 205 deaths per 100,000 persons annually
      and is the leading cause of death worldwide. The public health burden of
      cardiovascular disease is expected to continue to grow as the prevalence of many
      cardiovascular risk factors increases. Several novel classes of glucose-lowering,
      lipid-lowering, and weight-loss therapeutics have shown mortality benefits in
      outcomes trials. However, a large proportion of subjects in those trials had
      established cardiovascular disease, so, as a result, the role of these novel
      therapeutics in primary cardiovascular prevention is controversial. In this
      review, we highlight recent advances in the pharmacotherapeutic management of the
      cardiovascular risk factors of hyperglycemia, dyslipidemia, and obesity. We
      examine key subgroups within recent cardiovascular outcome trials, weigh the
      risks and benefits of several novel therapeutics, and provide practical insight
      into the use of these agents. Our article concludes with a look toward the future
      and provides the practitioner and scientist with an early view of emerging
      therapeutics that may play an important role in primary cardiovascular
      prevention.

PMID- 30201241
TI  - The tradeoff of cancer drug regulatory policy: Faster approvals for one means
      less knowledge for another.

PMID- 30201242
TI  - The Case for Confirmation: Atrial Flutter.

PMID- 30201243
TI  - Keep an Eye on the Eye Symptoms of Your Dialysis Patient.

PMID- 30201244
TI  - Medicine in the artistry of Menzel.

PMID- 30201245
TI  - Monitoring of apixaban in a super obese patient.

PMID- 30201246
TI  - Down the Rabbit Hole: Cutaneous Tuberculosis.

PMID- 30201247
TI  - Lift Then Shift: Thyrotoxic Periodic Paralysis.

PMID- 30201248
TI  - DOUBLING OF HEMOGLOBIN A1C ON PCSK 9 INHIBITOR THERAPY.

PMID- 30201249
TI  - Betrixaban: Safely Reducing Venous Thromboembolic Events with Extended
      Prophylaxis.
AB  - Although venous thromboembolism prophylaxis of acute medically ill patients is
      commonly employed, a percentage of high-risk patients still have venous
      thromboembolic events within 30 days of discharge. Research over the last several
      years has attempted to identify characteristics of these high-risk patients to
      facilitate provision of extended prophylaxis and venous thromboembolic event
      reduction. However, extended prophylaxis has been associated with a significant
      increase in the risk for major bleeding until recently. Betrixaban, a new oral
      direct Xa-inhibitor with once daily dosing and limited renal elimination,
      significantly reduces risk of venous thromboembolism without increasing risk for
      major bleeding. Consequently, betrixaban is the only anticoagulant approved by
      the Food and Drug Administration for preventing venous thromboembolism with
      extended prophylaxis in acute medically ill patients.

PMID- 30201251
TI  - Pelvis and femur geometry: Relationships with impact characteristics during
      sideways falls on the hip.
AB  - While metrics of pelvis and femur geometry have been demonstrated to influence
      hip fracture risk, attempts at linking geometry to underlying mechanisms have
      focused on fracture strength. We investigated the potential effects of femur and
      pelvis geometry on applied loads during lateral falls on the hip. Fifteen female
      volunteers underwent DXA imaging to characterize two pelvis and six femur
      geometric features. Additionally, participants completed low-energy sideways
      falls on the hip; peak impact force and pressure, contact area, and moment of
      force applied to the proximal femur were extracted. No geometric feature was
      significantly associated with peak impact force. Peak moment of force was
      significantly associated with femur moment arm (p = 0.005). Peak pressure was
      positively correlated with pelvis width and femur moment arm (p < 0.05), while
      contact area was negatively correlated with metrics of pelvis width and femur
      neck length (p < 0.05). This is the first study to link experimental measures of
      impact loads during sideways falls with image-based skeletal geometry from human
      volunteers. The results suggest that while skeletal geometry has limited effects
      on overall peak impact force during sideways falls, it does influence how impact
      loads are distributed at the skin surface, in addition to the bending moment
      applied to the proximal femur. These findings have implications for the design of
      protective interventions (e.g. wearable hip protectors), and for models of fall
      related lateral impacts that could incorporate the relationships between skeletal
      geometry, external load magnitude/distribution, and tissue-level femur loads.

PMID- 30201250
TI  - Harmonizing finite element modelling for non-invasive strength estimation by high
      resolution peripheral quantitative computed tomography.
AB  - The finite element (FE) method based on high-resolution peripheral quantitative
      computed tomography (HR-pQCT) use a variety of tissue constitutive properties and
      boundary conditions at different laboratories making comparison of mechanical
      properties difficult. Furthermore, the advent of a second-generation HR-pQCT
      poses challenges due to improved resolution and a larger region of interest
      (ROI). This study addresses the need to harmonize results across FE models. The
      aims are to establish the relationship between FE results as a function of
      boundary conditions and a range of tissue properties for the first-generation HR
      pQCT system, and to determine appropriate model parameters for the second
      generation HR-pQCT system. We implemented common boundary conditions and tissue
      properties on a large cohort (N = 1371), and showed the relationships were highly
      linear (R2 > 0.99) for yield strength and reaction force between FE models.
      Cadaver radii measured on both generation HR-pQCT with matched ROIs were used to
      back-calculate a tissue modulus that accounts for the increased resolution (61 um
      versus 82 um), resulting in a modulus of 8748 MPa for second-generation HR-pQCT
      to produce bone yield strength and reaction force equivalent to using 6829 MPa
      for first-generation HR-pQCT. Finally, in vivo scans (N = 61) conducted on both
      generations demonstrated that the larger ROI in the second-generation system
      results in stronger bone outcome measures, suggesting it is not advisable to
      convert FE results across HR-pQCT generations without matching ROIs. Together,
      these findings harmonize FE results by providing a means to compare findings with
      different boundary conditions and tissue properties, and across scanner
      generations.

PMID- 30201252
TI  - Development and evaluation of a new methodology for the fast generation of
      patient-specific Finite Element models of the buttock for sitting-acquired deep
      tissue injury prevention.
AB  - The occurrence and management of Pressure Ulcers remain a major issue for
      patients with reduced mobility and neurosensory loss despite significant
      improvement in the prevention methods. These injuries are caused by biological
      cascades leading from a given mechanical loading state in tissues to irreversible
      tissue damage. Estimating the internal mechanical conditions within loaded soft
      tissues has the potential of improving the management and prevention of PU.
      Several Finite Element models of the buttock have therefore been proposed based
      on either MRI or CT-Scan data. However, because of the limited availability of
      MRI or CT-Scan systems and of the long segmentation time, all studies in the
      literature include the data of only one individual. Yet the inter-individual
      variability can't be overlooked when dealing with patient specific estimation of
      internal tissue loading. As an alternative, this contribution focuses on the
      combined use of low-dose biplanar X-ray images, B-mode ultrasound images and
      optical scanner acquisitions in a non-weight-bearing sitting posture for the fast
      generation of patient-specific FE models of the buttock. Model calibration was
      performed based on Ischial Tuberosity sagging. Model evaluation was performed by
      comparing the simulated contact pressure with experimental observations on a
      population of 6 healthy subjects. Analysis of the models confirmed the high inter
      individual variability of soft tissue response (maximum Green Lagrange shear
      strains of 213 +/- 101% in the muscle). This methodology opens the way for
      investigating inter-individual factors influencing the soft tissue response
      during sitting and for providing tools to assess PU risk.

PMID- 30201253
TI  - Prognostic Effect of Renal Function in Ambulatory Patients With Heart Failure and
      Reduced Ejection Fraction: The Kidney Is a Marker of Cardiac Function.
AB  - BACKGROUND: Chronic kidney disease is a frequent comorbidity in heart failure
      (HF), associated with increased mortality. The impact of temporal evolution of
      kidney function in HF prognosis is largely unknown. We evaluated the effect of
      renal function over time in all-cause mortality among ambulatory patients with
      HF. METHODS: We retrospectively analyzed data from 560 patients with HF with left
      ventricular systolic dysfunction followed for a median of 25.1 months at an
      outpatient clinic. Demographics and comorbidities were collected at baseline.
      Creatinine values were abstracted from records at each clinical visit. Kidney
      function was assessed by estimated glomerular filtration rate (eGFR) and was
      categorized into 3 classes. Extended Cox models were performed to study the
      association between time-varying eGFR and death. RESULTS: Patients' mean age was
      67.5 +/- 13.9 years, 67.0% were men, 46.1% had ischemic etiology, the majority
      had moderate-to-severe left ventricular systolic dysfunction, and 45.9% had
      chronic kidney disease at baseline. The eGFR declined approximately 9.0
      mL/min/1.73 m2 over 5 years. In crude analysis, time-varying eGFR had a
      significant dose-dependent association with death (hazard ratio [HR] = 1.34, 95%
      confidence interval [CI]: 1.03-1.75 for eGFR between 30 and 60 mL/min/1.73 m2; HR
      = 1.55, 95% CI: 1.11-2.17 for <30 mL/min/1.73 m2). The prognostic value of time
      varying eGFR was totally explained by baseline comorbidities, indicators of HF
      severity and drugs (adjusted HR = 1.11, 95% CI: 0.83-1.48; HR = 1.19, 95% CI:
      0.79-1.80, for eGFR 30-60 and <30 mL/min/m2, respectively). CONCLUSIONS: Time
      varying kidney function is not independently related to poor prognosis in HF.
      Rather than directly affecting survival, renal impairment is probably a surrogate
      marker of HF severity.

PMID- 30201254
TI  - Cardiac Rehabilitation in Patients With Lymphoma Undergoing Autologous
      Hematopoietic Stem Cell Transplantation: A Cardio-oncology Pilot Project.
AB  - BACKGROUND: Worldwide > 50,000 hematopoietic stem cell transplants (HSCTs) are
      performed annually. HSCT patients receive multiple cardiotoxic therapies
      (chemotherapy and radiation therapy) in addition to severe physical
      deconditioning during hospital admission. We hypothesized that guided exercise in
      a cardiac rehabilitation (CR) program following autologous HSCT is a safe and
      feasible intervention. METHODS: Pilot project to assess for safety, feasibility
      and impact of 8 weeks of CR in HSCT patients following transplant. Consecutive
      patients with lymphoma underwent standard activity protocol testing before HSCT,
      at 6 weeks following HSCT (prior to CR), and at 14 weeks following HSCT (at
      completion of CR), consisting of grip strength (GS), gait speed (GtS), timed up
      and-go (TUG), and 6-minute walk test (6MWT). CR consisted of 8 weekly visits for
      guided exercise. RESULTS: Activity tolerance protocol data of 30 patients (24
      male, 6 female) from December 2014 to December 2016 were analyzed using repeated
      measures (analysis of variance [ANOVA]) to observe for changes in GS, GtS, TUG,
      and 6MWT. Statistically significant improvements were found in GS (P < 0.005),
      GtS (P = 0.02), and 6MWT (P = 0.001). These improvements show that guided CR
      based exercise may assist HSCT survivors to meet or even surpass baseline
      exercise levels and improve physical functioning. There were no adverse events
      (ie, death or injury) during the study period. Fifty-seven percent of referred
      patients participated in CR, exceeding documented CR adherence in cardiac
      populations. CONCLUSIONS: The addition of CR-based exercise programming in HSCT
      survivorship care of patients with lymphoma is a safe and feasible intervention
      to assist in recovery following transplant.

PMID- 30201255
TI  - Integrating Individuals With Stroke Into Cardiac Rehabilitation Following
      Traditional Stroke Rehabilitation: Promoting a Continuum of Care.
AB  - Following stroke, people are at high risk for repeat strokes and for
      complications related to coronary artery disease (CAD). Indeed, stroke and CAD
      share many of the same risk factors. Unfortunately, patients become sedentary
      after stroke, which leads to cardiorespiratory deconditioning as well as muscle
      atrophy and weakness that in turn leads to deterioration in metabolic,
      cardiorespiratory, and functional health. Access to intensive secondary
      prevention programs with structured exercise components that include both aerobic
      and resistance training can help to prevent and reverse these health hazards.
      Traditional stroke rehabilitation programs face many barriers to providing
      exercise programming early post-stroke, such as lack of available therapy time
      and short length of stay, lack of equipment for exercise and assessments, and
      concerns for patient safety related to cardiac status. Building a partnership
      between traditional stroke rehabilitation programs and cardiac rehabilitation by
      operationalizing an automatic referral process has the potential to affect
      secondary prevention of stroke and cardiovascular risk significantly. It could
      also mitigate the tremendous burden on patients and their family members. This is
      an easily identified group that can achieve significant gains over multiple
      domains of recovery with the targeted exercise and risk-factor modification
      components offered by comprehensive cardiac rehabilitation programs.

PMID- 30201256
TI  - Effects of short-term intravaginal progestagens on the onset and features of
      estrus, preovulatory LH surge and ovulation in sheep.
AB  - In the present study, there was a comparison among classical long-term
      progestagen (fluorogestone acetate) protocols for synchronization of estrus and
      ovulation (14 days; group FGA14, n = 9 ewes) and short-term protocols based on 7
      days of progestagen treatment plus a dose of prostaglandin F2alpha at either
      insertion (PG-FGA7, n = 11) or removal (FGA7-PG, n = 12). There were no
      significant differences in the ovulation rate and progesterone secretion among
      treatments. The FGA7-PG group, however, had a similar percentage of ewes
      expressing estrous behavior than the group FGA14 (90.9 and 100%, respectively,
      with a trend for a lesser percentage in the PG-FGA7 group, 63.6%) and about 90%
      of the ewes in the FGA7-PG group had the preovulatory surge release of LH 8 h
      after the onset of estrous behavior. These features may be related to a greater
      number of preovulatory follicles during growing phases (P < 0.05) and a greater
      plasma estradiol concentration (P < 0.05) in this group than in the classical 14
      day group, which suggest these are more functional preovulatory follicles. In
      conclusion, therefore, the use of the FGA7-PG treatment may favor efficiency of
      progestagen-based protocols for reproductive management.

PMID- 30201257
TI  - Nonsecretory and Light Chain Escape in Patients With Multiple Myeloma.
AB  - BACKGROUND: Multiple myeloma (MM) is characterized by the secretion of monoclonal
      protein by malignant plasma cells in the vast majority of cases. We identified
      and analyzed patterns of disease relapse and progression associated with
      disappearance of the paraprotein ("nonsecretory [NS] escape"), or conversion from
      production of intact Ig molecule to its associated light chain ("LC escape").
      PATIENTS AND METHODS: We retrospectively reviewed medical records and a database
      of 791 consecutive patients with symptomatic MM. RESULTS: Twenty-eight (3.5%)
      patients had disease evolution associated with either NS (n = 13) or LC (n = 15)
      escape. The event occurred at a median of 37 months (range, 3-156 months) after
      the diagnosis of MM, and after a median of 3 chemotherapy regimens (range, 1-8
      regimens). Presence of extramedullary disease at progression was detected in 8
      (29%) patients. Sensitivity to chemotherapy before and after escape was present
      in 21 (75%) and 14 (50%) patients, respectively. After a median follow-up of 55
      months, 19 (68%) patients died, and progressive MM was the cause of death in 18
      patients. The median overall survival after escape was 20 months (95% confidence
      interval, 9-25 months), and no significant difference was found between the NS
      and LC groups (P = .44). The median overall survival after diagnosis of MM was
      worse in patients with NS/LC escape than in those without escape (52 vs. 94
      months; P = .018). CONCLUSIONS: Our study describes the largest series of NS and
      LC escape in MM to date. The development of this phenomenon is associated with
      more aggressive clinical features, frequent resistance to chemotherapy, and worse
      clinical outcome.

PMID- 30201258
TI  - The artificial sweetener Splenda intake promotes changes in expression of c-Fos
      and NeuN in hypothalamus and hippocampus of rats.
AB  - BACKGROUND: Obesity is the result of the interaction of multiple variables,
      including the excessive increase of sugar-sweetened beverages consumption. Diets
      aimed to treat obesity have suggested the use of artificial sweeteners. However,
      recent evidence has shown several health deficits after intake of artificial
      sweeteners, including effects in neuronal activity. Therefore, the influence of
      artificial sweeteners consumption such as Splenda, on the expression of c-Fos and
      neuronal nuclear protein (NeuN) in hypothalamus and hippocampus remains to be
      determined. OBJECTIVES: We investigated the effects on c-Fos or NeuN expression
      in hypothalamus and hippocampus of Splenda-treated rats. METHODS: Splenda was
      diluted in water (25, 75 or 250 mg/100 mL) and orally given to rats during 2
      weeks ad libitum. Next, animals were sacrificed by decapitation and brains were
      collected for analysis of c-Fos or NeuN immunoreactivity. RESULTS: Consumption of
      Splenda provoked an inverted U-shaped dose-effect in c-Fos expression in
      ventromedial hypothalamic nucleus while similar findings were observed in dentate
      gyrus of hippocampus. In addition, NeuN immunoreactivity was enhanced in
      ventromedial hypothalamic nucleus at 25 or 75 mg/100 mL of Splenda intake whereas
      an opposite effect was observed at 250 mg/100 mL of artificial sweetener
      consumption. Lastly, NeuN positive neurons were increased in CA2/CA3 fields of
      hippocampus from Splenda-treated rats (25, 75 or 250 mg/100 mL). CONCLUSION:
      Consuming Splenda induced effects in neuronal biomarkers expression. To our
      knowledge, this study is the first description of the impact of intake Splenda on
      c-Fos and NeuN immunoreactivity in hypothalamus and hippocampus in rats.

PMID- 30201259
TI  - Double-edged GABAergic synaptic transmission in seizures: The importance of
      chloride plasticity.
AB  - GABAergic synaptic inhibition, which is a critical regulator of neuronal
      excitability, is closely involved in epilepsy. Interestingly, fast GABAergic
      transmission mediated by Cl- permeable GABAA receptors can bi-directionally exert
      both seizure-suppressing and seizure-promoting actions. Accumulating evidence
      suggests that chloride plasticity, the driving force of GABAA receptor-mediated
      synaptic transmission, contributes to the double-edged role of GABAergic synapses
      in seizures. Large amounts of Cl- influx can overwhelm Cl- extrusion during
      seizures not only in healthy tissue in a short-term "activity-dependent" manner,
      but also in chronic epilepsy in a long-term, irreversible "pathology-dependent"
      manner related to the dysfunction of two chloride transporters: the chloride
      importer NKCC1 and the chloride exporter KCC2. In this review, we address the
      importance of chloride plasticity for the "activity-dependent" and "pathology
      dependent" mechanisms underlying epileptic events and provide possible directions
      for further research, which may be clinically important for the design of
      GABAergic synapse-targeted precise therapeutic interventions for epilepsy.

PMID- 30201260
TI  - Dexmedetomidine alleviates cerebral ischemia-reperfusion injury by inhibiting
      endoplasmic reticulum stress dependent apoptosis through the PERK-CHOP-Caspase-11
      pathway.
AB  - Dexmedetomidine (Dex) has the neuroprotective effect on cerebral ischemia
      reperfusion injury (CIRI). But the mechanism is not yet clear. In this study, we
      established a model of middle cerebral artery occlusion (MCAO) and treated
      primary cortical neurons with oxygen glucose deprivation (OGD), followed by Dex
      treatment. Neurological protection of Dex was then assessed by neurological
      deficit score, brain edema, TTC staining, TUNEL assay, Western blot analysis,
      immunohistochemistry, and RT-PCR. The results showed that Dex significantly
      reduced the neurological deficit score, brain edema and cerebral infarction area
      due to CIRI. After Dex treatment, the expression levels of ER stress-related
      apoptosis pathway proteins (GRP78, p-PERK, CHOP and Cleaved-caspase-3) were
      significantly decreased and the apoptosis of brain cells was also significantly
      reduced. Immunohistochemistry showed that expression and nuclear localization of
      CHOP decreased significantly after the application of Dex. The downstream
      apoptotic protein caspase-11 mediated by PERK-CHOP was also markedly inhibited by
      Dex. In conclusion, our results suggested that Dex reduced ER stress-induced
      apoptosis after CIRI. Its protective mechanism may be related to PERK-CHOP
      Caspase-11 dependent signaling pathway.

PMID- 30201261
TI  - Role of angiopoietins in mesothelioma progression.
AB  - BACKGROUND AND OBJECTIVE: Anti-angiogenic treatment has been recently shown to be
      clinically beneficial for mesothelioma patients. Angiopoietins-1 and -2 are key
      regulators of tumor angiogenesis. Ang-1 is mainly known to promote angiogenesis
      and vessel stability, while Ang-2 could serve as an antagonist of Ang-1 causing
      vessel regression and destabilization or enhance angiogenesis in a context
      dependent manner. We hypothesized that Ang-1 would promote and Ang2 would halt
      experimental mesothelioma by affecting tumor angiogenesis. METHODS: To examine
      the effects of angiopoietins in mesothelioma angiogenesis and in vivo growth we
      constructed Ang-1 or Ang-2 overexpressing AE17 and AB1 mesothelioma cells and
      implanted them in the respective syngeneic animals. We also explored the clinical
      relevance of our observations using the human tumoral mRNAseq data available in
      the TCGA database. RESULTS AND CONCLUSIONS: Ang-1 promotes mesothelioma
      angiogenesis and growth while the effect of Ang-2 is context-dependent. Low Ang-1
      levels in human mesotheliomas are associated with the epitheloid subtype. Tumors
      of high Ang-1, or concurrent high Ang-2 and VEGF expression present high PECAM-1
      and CDH5 expression, markers of vascularity and vascular stability, respectively.
      Our results highlight the importance of angiopoietins in mesothelioma
      pathophysiology and pave the way for the clinical development of novel anti
      angiogenic strategies.

PMID- 30201262
TI  - Fission yeast Adf1 is necessary for reassembly of actin filaments into the
      contractile ring during cytokinesis.
AB  - ADF/cofilin family proteins quickly disassemble actin in vitro, and are thought
      to be involved in various actin dynamics in the cell. Adf1 is a member of this
      family proteins expressed in fission yeast, and is thought to play roles in actin
      patch dynamics and also contractile ring formation during cytokinesis. We aimed
      to understand the function of this protein in cytokinesis in detail using the
      temperature-sensitive mutant adf1-1. Adf1 inactivation at a restrictive
      temperature during late G2 phase led to a clustering of actin patches at the cell
      ends. It was apparent that the inactivation occurred only in a few minutes.
      Furthermore, we found that the actin clusters migrated to the division site
      during anaphase possibly by the function of both myosin 5-1 and a myosin II. The
      migrated actin clusters, however, were not organized into the contractile ring.
      When Adf1 was inactivated at mid-anaphase B before contractile ring assembly, the
      ring was not formed, but it was formed when Adf1 was inactivated after this
      point. We conclude that Adf1 functions in the interphase actin dynamics and
      formation of the contractile ring during mitosis.

PMID- 30201263
TI  - Ropivacaine impairs mitochondrial biogenesis by reducing PGC-1alpha.
AB  - Ropivacaine is one of the commonly used local anesthetics in medical and dental
      care. However, preclinical and observational studies indicate that ropivacaine
      could have substantial side effects including neurotoxicity, which has raised
      concern regarding the safety of this drug. In the present study, we investigated
      the effects of clinically relevant doses of ropivacaine on mitochondrial
      biogenesis and function in neuronal cells. Our data indicate that exposure to
      ropivacaine leads to reduced expression of the major mitochondrial regulator PGC
      1alpha and its downstream transcription factors NRF1 and TFAM. Ropivacaine
      treatment induces impairment of mitochondrial biogenesis by reducing
      mitochondrial mass, the ratio of mtDNA to nDNA (mtDNA/nDNA), cytochrome C oxidase
      activity, and COX-1 expression. Additionally, treatment with ropivacaine causes
      "loss of mitochondrial function" by impairing the mitochondrial respiratory rate
      and ATP production. Mechanistically, the reduction of PGC-1alpha caused by
      ropivacaine exposure requires inactivation of CREB, while re-introduction of PGC
      1alpha completely rescues ropivacaine-induced mitochondrial abnormalities. In
      summary, our results provide supporting evidence that mitochondrial impairment is
      a key event in ropivacaine-mediated neurotoxicity, and the reduction of PGC
      1alpha and its downstream signals are likely the molecular mechanism behind its
      cellular toxicity.

PMID- 30201264
TI  - The TORC1-Nem1/Spo7-Pah1/lipin axis regulates microautophagy induction in budding
      yeast.
AB  - Nutrient starvation and inactivation of target of rapamycin complex 1 (TORC1)
      protein kinase promotes macroautophagy. Macroautophagy is a lipid-consuming
      process, and Nem1/Spo7 protein phosphatase and Pah1/lipin phosphatidate
      phosphatase are activated after TORC1 inactivation, supporting macroautophagy
      induction in the budding yeast Saccharomyces cerevisiae. On the other hand,
      whether and how microautophagy, which also consumes lipids, is regulated by TORC1
      is controversial. Here we show that TORC1 inactivation induces microautophagy in
      budding yeast. Vps27, but not Atg1, Atg7, or Atg8, was required for TORC1
      inactivation-induced microautophagy. Furthermore, the Nem1/Spo7-Pah1 axis was
      also critical for microautophagy induction. Thus, the TORC1-Nem1/Spo7-Pah1 axis
      is a master regulator of not only macroautophagy but also microautophagy in
      budding yeast.

PMID- 30201265
TI  - Platelet-derived growth factor receptor alpha (PDGFRalpha) is overexpressed in
      NK/T-cell lymphoma and mediates cell survival.
AB  - Nasal-type natural killer/T-cell lymphoma (NKTCL) is a subtype of non-Hodgkin
      lymphoma (NHL) that is clinically aggressive and has a poor prognosis. Platelet
      derived growth factor receptors (PDGFRs) and their ligands (PDGFs) play important
      roles in angiogenesis, cancer cell proliferation, survival, migration and poor
      prognosis in various tumours. However, the significance of PDGFRs in NKTCL
      remains unknown. Herein, the present study aimed to investigate the important
      role of PDGFRalpha in pathogenesis, progression and prognisis of NKTCL. Firstly,
      we performed immunohistochemical staining, qRT-PCR and western blotting to
      determine PDGFRalpha expression in formalin-fixed, paraffin-embedded tissue
      sections from 78 NKTCL cases and in cell lines. Secondly, correlations between
      PDGFRalpha expression and NKTCL clinical parameters and prognosis were analysed.
      Moreover, a biological assessment of PDGFRalpha blockade in two NKTCL cell lines
      was conducted through proliferation assay, cell-cycle evaluation and apoptosis
      detection by flow cytometry analyses. Furthermore, we detected in vivo activity
      of imatinib in mouse model of NKTCL. We found that the expression of PDGFRalpha
      was significantly higher in NKTCL tissues compared to the reactive lymphoid
      hyperplasia of the nasopharynx (P = 0.028). High PDGFRalpha expression was
      strongly associated with a high LDH level (P = 0.028) and III-IV stage (P =
      0.013). NKTCL patients with high PDGFRalpha expression displayed a reduced median
      overall survival time and progression-free survival time when compared with those
      with low PDGFRalpha expression (P = 0.011, P = 0.005, respectively). Cox
      multivariate analysis showed that III-IV stage (P = 0.024) and high PDGFRalpha
      expression (P = 0.003) were independent prognostic factors in NKTCL patients.
      Biological assessment assays in two NKTCL cell lines revealed that a specific
      PDGFR antagonist, imatinib, inhibited cell viability, blocked cell cycle
      progression at G0/G1 stage and induced apoptosis. Similarly, the in vivo assay
      showed that imatinib delayed mouse model tumour growth. In conclusion, NKTCL
      tumour cells have prominent PDGFRalpha expression, which can serve as a candidate
      prognostic marker. PDGFR antagonists have significant biological effect on NKTCL
      and may be useful therapeutic agents for treatment of NKTCL.

PMID- 30201266
TI  - Extravasation of Brownian Spheroidal Nanoparticles through Vascular Pores.
AB  - In modern cancer treatment, there is significant interest in studying the use of
      drug molecules either directly injected into the bloodstream or delivered by
      nanoparticle (NP) carriers of various shapes and sizes. During treatment, these
      carriers may extravasate through pores in the tumor vasculature that form during
      angiogenesis. We provide an analytical, computational, and experimental
      examination of the extravasation of point particles (e.g., drug molecules) and
      finite-sized spheroidal particles. We study the advection-diffusion process in a
      model microvasculature, consisting of a shear flow over and a pressure-driven
      suction flow into a circular pore in a flat surface. For point particles, we
      provide an analytical formula [Formula: see text] for the dimensionless Sherwood
      number S, i.e., the extravasation rate, in terms of the pore entry resistance
      (Damkohler number kappa), the shear rate (Peclet number P), and the suction flow
      rate (suction strength Q). Brownian dynamics (BD) simulations verify this result,
      and our simulations are then extended to include finite-sized NPs, in which no
      analytical solutions are available. BD simulations indicate that particles of
      different geometries have drastically different extravasation rates in different
      flow conditions. In general, extreme aspect ratio particles provide a greater
      flux through the pore because of favorable alignment with streamlines entering
      the pore and less hindered interaction with the pore. We validate the BD
      simulations by measuring the in vitro transport of both bacteriophage MS2 (a
      spherical NP) and free dye (a model drug molecule) across a porous membrane.
      Despite their vastly different sizes, BD predicts S = 8.53 E-4 and S = 27.6 E-4,
      and our experiments agree favorably, with Sexp=10.6 E-4+/- 1.75 E-4 and Sexp=16.3
      E-4 +/- 3.09 E-4, for MS2 and free dye, respectively, thus demonstrating the
      practical utility of our simulation framework.

PMID- 30201267
TI  - Dynamic Interplay of RNA and Protein in the Human Immunodeficiency Virus-1
      Reverse Transcription Initiation Complex.
AB  - The initiation of reverse transcription in human immunodeficiency virus-1 is a
      key early step in the virus replication cycle. During this process, the viral
      enzyme reverse transcriptase (RT) copies the single-stranded viral RNA (vRNA)
      genome into double-stranded DNA using human tRNALys3 as a primer for initiation.
      The tRNA primer and vRNA genome contain several complementary sequences that are
      important for regulating reverse transcription initiation kinetics. Using single
      molecule Forster resonance energy transfer spectroscopy, we demonstrate that the
      vRNA-tRNA initiation complex is conformationally heterogeneous and dynamic in the
      absence of RT. As shown previously, nucleic acid-RT interaction is characterized
      by rapid dissociation constants. We show that extension of the vRNA-tRNA primer
      binding site helix from 18 base pairs to 22 base pairs stabilizes RT binding to
      the complex and that the tRNA 5' end has a role in modulating RT binding. RT
      occupancy on the complex stabilizes helix 1 formation and reduces global
      structural heterogeneity. The stabilization of helix 1 upon RT binding may serve
      to destabilize helix 2, the first pause site for RT during initiation, during
      later steps of reverse transcription initiation.

PMID- 30201268
TI  - Preventing hypoesthesia after a buccal plate fracture in a sagittal split
      procedure: A technical note.
AB  - If during a sagittal split osteotomy a buccal plate fracture occurs, it
      inevitably results in a time-consuming procedure with, in many cases,
      hypoesthesia of the mental region as a consequence of manipulation of the
      inferior alveolar nerve. We would like to present a novel technique to solve a
      (threatening) buccal plate fracture that is quick and easy to perform, and has
      thus far not resulted in hypoesthesia.

PMID- 30201269
TI  - Biomechanical evaluation of lumbar lateral interbody fusion for the treatment of
      adjacent segment disease.
AB  - BACKGROUND CONTEXT: Adjacent segment disease (ASD) is a well-known complication
      after lumbar fusion. Lumbar lateral interbody fusion (LLIF) may provide an
      alternative method of treatment for ASD while avoiding the morbidity associated
      with revision surgery through a traditional posterior approach. This is the first
      biomechanical study to evaluate the stability of lateral-based constructs for
      treating ASD in existing multilevel fusion model. PURPOSE: We aimed to evaluate
      the biomechanical stability of anterior column reconstruction through the less
      invasive lateral-based interbody techniques compared with traditional posterior
      spinal fusion for the treatment of ASD in existing multilevel fusion. STUDY
      DESIGN/SETTING: Cadaveric biomechanical study of laterally based interbody
      strategies for treating ASD. METHODS: Eighteen fresh-frozen cadaveric specimens
      were nondestructively loaded in flexion, extension, and lateral bending. The
      specimens were randomized into three different groups according to planned
      posterior spinal instrumented fusion (PSF): group 1: L5-S1, group 2: L4-S1, and
      group 3: L3-S1. In each group, ASD was considered the level cranial to the upper
      instrumented vertebrae (UIV). After testing the intact spine, each specimen
      underwent PSF representing prior fusion in the ASD model. The adjacent segment
      for each specimen then underwent (1) Stand-alone LLIF, (2) LLIF + plate, (3) LLIF
      + single screw rod (SSR) anterior instrumentation, and (4) LLIF + traditional
      posterior extension of PSF. In all conditions, three-dimensional kinematics were
      tracked, and range of motion (ROM) was calculated for the comparisons. RESULTS:
      ROM results were expressed as a percentage of the intact spine ROM. LLIF
      effectively reduces ROM in all planes of ROM. Supplementation of LLIF with plate
      or SSR provides further stability as compared with stand-alone LLIF. Expansion of
      posterior instrumentation provides the most substantial stability in all planes
      of ROM (p <.05). All constructs demonstrated a consistent trend of reduction in
      ROM between all the groups in all bending motions. CONCLUSIONS: This
      biomechanical study suggests potential promise in exploring LLIF as an
      alternative treatment of ASD but reinforces previous studies' findings that
      traditional expansion of posterior instrumentation provides the most
      biomechanically stable construct.

PMID- 30201270
TI  - Kill 'Em All: Efgartigimod Immunotherapy for Autoimmune Diseases.
AB  - Neonatal Fc receptors (FcRns) recycle IgGs by preventing their lysosome
      degradation. As this process also enhances half-life of pathogenic auto-IgG,
      inspired from the mechanisms of intravenous immunoglobulin, several inhibitors of
      IgG-FcRn interface have been conceived for treating autoimmune diseases. Among
      them, the high-affinity FcRn-binding engineered Fc molecule efgartigimod has
      recently completed phase I clinical trial.

PMID- 30201272
TI  - Addressing the fragmentation of global health: the Lancet Commission on synergies
      between universal health coverage, health security, and health promotion.

PMID- 30201273
TI  - Does the exposure to salinity variations and water dispersible carbon nanotubes
      induce oxidative stress in Hediste diversicolor?
AB  - Salinity plays a fundamental role in naturally fluctuating environments such as
      estuaries influencing physiological and biochemical performance of inhabiting
      biota. Moreover salinity is considered one of the main factors influencing
      nanoparticles' stability. Thus, the aim of the present paper was to show the
      impacts induced by different salinities (control-28 and 21) on the chemical
      behavior of water dispersible multi-walled carbon nanotube (MWCNTs-COOH) and the
      consequent toxicity in the common ragworm Hediste diversicolor, after long term
      exposure. Results showed a concentration-dependent toxicity in terms of energy
      reserves and metabolism, oxidative status and neurotoxicity. In addition, under
      low salinity (21), the toxicity of the carbon NMs was similar to the impacts
      measured under control (28), although under salinity 28 the concentrations of
      MWCNTs-COOH used generated greater alterations in LPO levels and antioxidant
      enzymes (SOD and GPx). These results demonstrate that higher salinity caused the
      formation of large-size aggregates, which increased the chance of physical
      retention, such as gravitational sedimentation, interception and straining of f
      MWCNTs generating higher cell injuries than the impacts induced in polychaetes
      sensitivity to these contaminates due to low salinity.

PMID- 30201271
TI  - ESM-CT: a precise method for localization of DBS electrodes in CT images.
AB  - BACKGROUND: Deep brain stimulation (DBS) of the subthalamic nucleus produces
      variable effects in Parkinson disease. Variation may result from different
      electrode positions relative to target. Thus, precise electrode localization is
      crucial when investigating DBS effects. NEW METHOD: We developed a semi-automated
      method, Electrode Shaft Modeling in CT images (ESM-CT) to reconstruct DBS lead
      trajectories and contact locations. We evaluated methodological sensitivity to
      operator-dependent steps, robustness to image resampling, and test-retest
      replicability. ESM-CT was applied in 56 patients to study electrode position
      change (and relation to time between scans, postoperative subdural air volume,
      and head tilt during acquisition) between images acquired immediately post
      implantation (DBS-CT) and months later (DEL-CT). RESULTS: Electrode tip
      localization was robust to image resampling and replicable to within ~ 0.2 mm on
      test-retest comparisons. Systematic electrode displacement occurred rostral
      ventral-lateral between DBS-CT and DEL-CT scans. Head angle was a major
      explanatory factor (p < 0.001,Pearson's r = 0.46, both sides) and volume of
      subdural air weakly predicted electrode displacement (p = 0.02,r = 0.29:p = 0.1,r
      = 0.25 for left:right). Modeled shaft curvature was slightly greater in DEL-CT.
      Magnitude of displacement and degree of curvature were independent of elapsed
      time between scans. COMPARISON WITH EXISTING METHODS: Comparison of ESM-CT
      against two existing methods revealed systematic differences in one coordinate (1
      +/- 0.3 mm,p < 0.001) for one method and in three coordinates for another method
      (x:0.1 +/- 0.1 mm, y:0.4 +/- 0.2 mm, z:0.4 +/- 0.2 mm, p < 10-10). Within-method
      coordinate variability across participants is similar. CONCLUSION: We describe a
      robust and precise method for CT DBS contact localization. Application revealed
      that acquisition head angle significantly impacts electrode position. DBS
      localization schemes should account for head angle.

PMID- 30201276
TI  - Adaptive Radiotherapy Enabled by MRI Guidance.
AB  - Adaptive radiotherapy (ART) strategies systematically monitor variations in
      target and neighbouring structures to inform treatment-plan modification during
      radiotherapy. This is necessary because a single plan designed before treatment
      is insufficient to capture the actual dose delivered to the target and adjacent
      critical structures during the course of radiotherapy. Magnetic resonance imaging
      (MRI) provides superior soft-tissue image contrast over current standard X-ray
      based technologies without additional radiation exposure. With integrated MRI and
      radiotherapy platforms permitting motion monitoring during treatment delivery, it
      is possible that adaption can be informed by real-time anatomical imaging. This
      allows greater treatment accuracy in terms of dose delivered to target with
      smaller, individualised treatment margins. The use of functional MRI sequences
      would permit ART to be informed by imaging biomarkers, so allowing both
      personalised geometric and biological adaption. In this review, we discuss ART
      solutions enabled by MRI guidance and its potential gains for our patients across
      tumour types.

PMID- 30201274
TI  - T1R2 receptor-mediated glucose sensing in the upper intestine potentiates glucose
      absorption through activation of local regulatory pathways.
AB  - OBJECTIVE: Beyond the taste buds, sweet taste receptors (STRs; T1R2/T1R3) are
      also expressed on enteroendocrine cells, where they regulate gut peptide
      secretion but their regulatory function within the intestine is largely unknown.
      METHODS: Using T1R2-knock out (KO) mice we evaluated the role of STRs in the
      regulation of glucose absorption in vivo and in intact intestinal preparations ex
      vivo. RESULTS: STR signaling enhances the rate of intestinal glucose absorption
      specifically in response to the ingestion of a glucose-rich meal. These effects
      were mediated specifically by the regulation of GLUT2 transporter trafficking to
      the apical membrane of enterocytes. GLUT2 translocation and glucose transport was
      dependent and specific to glucagon-like peptide 2 (GLP-2) secretion and
      subsequent intestinal neuronal activation. Finally, high-sucrose feeding in wild
      type mice induced rapid downregulation of STRs in the gut, leading to reduced
      glucose absorption. CONCLUSIONS: Our studies demonstrate that STRs have evolved
      to modulate glucose absorption via the regulation of its transport and to prevent
      the development of exacerbated hyperglycemia due to the ingestion of high levels
      of sugars.

PMID- 30201277
TI  - Risk of Death from Pneumocystis jirovecii after Curative-intent Radiotherapy for
      Lung Cancer.

PMID- 30201278
TI  - Reinventing an Organelle: The Reduced Mitochondrion in Parasitic Protists.
AB  - Mitochondria originated from the endosymbiotic event commencing from the
      engulfment of an ancestral alpha-proteobacterium by the first eukaryotic
      ancestor. Establishment of niches has led to various adaptations among
      eukaryotes. In anaerobic parasitic protists, the mitochondria have undergone
      modifications by combining features shared from the aerobic mitochondria with
      lineage-specific components and mechanisms; a diversified class of organelles
      emerged and are generally called mitochondrion-related organelles (MROs). In this
      review we summarize and discuss the recent advances in the knowledge of MROs from
      parasitic protists, particularly the themes such as metabolic functions,
      contribution to parasitism, dynamics, protein targeting, and novel lineage-
      specific proteins, with emphasis on the diversity among these organelles.

PMID- 30201275
TI  - Quantitative mass spectrometry for human melanocortin peptides in vitro and in
      vivo suggests prominent roles for beta-MSH and desacetyl alpha-MSH in energy
      homeostasis.
AB  - OBJECTIVE: The lack of pro-opiomelanocortin (POMC)-derived melanocortin peptides
      results in hypoadrenalism and severe obesity in both humans and rodents that is
      treatable with synthetic melanocortins. However, there are significant
      differences in POMC processing between humans and rodents, and little is known
      about the relative physiological importance of POMC products in the human brain.
      The aim of this study was to determine which POMC-derived peptides are present in
      the human brain, to establish their relative concentrations, and to test if their
      production is dynamically regulated. METHODS: We analysed both fresh post-mortem
      human hypothalamic tissue and hypothalamic neurons derived from human pluripotent
      stem cells (hPSCs) using liquid chromatography tandem mass spectrometry (LC
      MS/MS) to determine the sequence and quantify the production of hypothalamic
      neuropeptides, including those derived from POMC. RESULTS: In both in vitro and
      in vivo hypothalamic cells, LC-MS/MS revealed the sequence of hundreds of
      neuropeptides as a resource for the field. Although the existence of beta
      melanocyte stimulating hormone (MSH) is controversial, we found that both this
      peptide and desacetyl alpha-MSH (d-alpha-MSH) were produced in considerable
      excess of acetylated alpha-MSH. In hPSC-derived hypothalamic neurons, these POMC
      derivatives were appropriately trafficked, secreted, and their production was
      significantly (P < 0.0001) increased in response to the hormone leptin.
      CONCLUSIONS: Our findings challenge the assumed pre-eminence of alpha-MSH and
      suggest that in humans, d-alpha-MSH and beta-MSH are likely to be the predominant
      physiological products acting on melanocortin receptors.

PMID- 30201279
TI  - Evaluation of Aspergillus and Mucorales specific T-cells and peripheral blood
      mononuclear cell cytokine signatures as biomarkers of environmental mold
      exposure.
AB  - Mold specific T-cells have been described as a supportive biomarker to monitor
      invasive mycoses and mold exposure. This study comparatively evaluated
      frequencies and cytokine profiles of Aspergillus fumigatus and Mucorales reactive
      T-cells depending on environmental mold exposure. Peripheral blood mononuclear
      cells (PBMCs) obtained from 35 healthy donors were stimulated with mycelial
      lysates of A. fumigatus and three human pathogenic Mucorales species. CD154+
      specific T-cells were quantified by flow cytometry. In a second cohort of 20
      additional donors, flow cytometry was complemented by 13-plex cytokine assays.
      Mold exposure of the subjects was determined using a previously established
      questionnaire. Highly exposed subjects exhibited significantly greater CD154+A.
      fumigatus and Mucorales specific naive and memory T-helper cell frequencies.
      Significant correlation (r = 0.48 - 0.79) was found between A. fumigatus and
      Mucorales specific T-cell numbers. Logistic regression analyses revealed that
      combined analysis of mold specific T-cell frequencies and selected cytokine
      markers (A. fumigatus: IL-5 and TNF-alpha, R. arrhizus: IL-17A and IL-13)
      significantly improves classification performance, resulting in 75-90 %
      predictive power using 10-fold cross-validation. In conclusion, mold specific T
      cell frequencies and their cytokine signatures offer promising potential in the
      assessment of environmental mold exposure. The cytokines identified in this pilot
      study should be validated in the clinical setting, e. g. in patients with
      hypersensitivity pneumonitis.

PMID- 30201280
TI  - Helicobacter pylori growth stimulation by adrenaline detected by two methods.
AB  - Our aim was to assess growth effects of adrenaline on 32 Helicobacter pylori
      strains on 2.5% blood agar. By agar-well diffusion and disk diffusion methods,
      concentration-dependent growth stimulation occurred in <=50.0% and 36.8% of the
      strains, respectively. Growth inhibition was less frequent. Most strains were
      adrenaline-responsive and growth stimulation prevailed.

PMID- 30201281
TI  - Gender Comparison of the Diet Quality and Sources of Food Purchases Made by Urban
      Primary Household Food Purchasers.
AB  - OBJECTIVE: To compare food purchasing behaviors and diet quality of foods
      purchased between men and women who were the primary food purchaser for their
      households. METHODS: Food purchasing was measured via itemized receipts. The
      dietary composition of purchased foods was derived using the Nutrition Data
      System for Research and quality was assessed using the Healthy Eating Index-2010.
      RESULTS: Men comprised 17.2% of the household primary food purchasers in the
      sample (n = 204). There were no differences by gender in the number of items
      purchased or the number of receipts. Men made fewer purchases at stores (74.0%)
      than did women (81.4%; P < .001). There were no gender differences in the quality
      of foods purchased overall or by source of purchase. CONCLUSIONS AND
      IMPLICATIONS: In primary purchasers, purchasing behaviors varied by gender but
      not purchases did not. Food purchasing interventions should include both genders
      for greatest impact.

PMID- 30201282
TI  - Being Motivated by Nutrition Is Associated With Healthy Home Food Environment of
      Supplemental Nutrition Assistance Program (SNAP) Recipients.
AB  - OBJECTIVE: To examine the relationship between food shopping motivating factors
      and the home food environment (HFE). METHODS: Participants in the Supplemental
      Nutrition Assistance Program (n = 123) who were taking part in the Utah State
      Double-Up Food Bucks evaluation program were interviewed about their HFE, factors
      motivating shopping, and food security status. Composite HFE scores were derived
      from the Perceived Nutrition Environment Measure Survey questionnaire and food
      security score from the 6-item US Household Food Security Survey questionnaire.
      Analysis included multiple linear regression. RESULTS: Mean age was 46 +/- 16.1
      years. Regression models showed significant associations of being motivated by
      nutrition, education, and food security with HFE (beta = 4.70, P = .03; beta =
      1.44, P = .06; and beta = 1.44, P = .06, respectively). CONCLUSION AND
      IMPLICATIONS: In-store interventions to improve perceived nutrition importance
      among shoppers may be a useful tool to improve home food supplies. Further
      research is recommended examining the association between food shopping
      motivators and the HFE in a larger population.

PMID- 30201283
TI  - Adaptive fuzzy integral sliding mode control of blood glucose level in patients
      with type 1 diabetes: In silico studies.
AB  - Currently, artificial pancreas is an alternative treatment instead of insulin
      therapy for patients with type 1 diabetes mellitus. Closed-loop control of blood
      glucose level (BGL) is one of the difficult tasks in biomedical engineering field
      due to nonlinear time-varying dynamics of insulin-glucose relation that is
      combined with time delays and model uncertainties. In this paper, we propose a
      novel adaptive fuzzy integral sliding mode control scheme for BGL regulation.
      System dynamics is identified online using fuzzy logic systems. The presented
      method is evaluated in silico studies by nine different virtual patients in three
      different groups for two continuous days. Simulation results demonstrate
      effective performance of the proposed control scheme of BGL regulation in
      presence of simultaneous meal and physical exercise disturbances. Comparison of
      the proposed control method with proportional-integral-derivative (PID) control
      and model predictive control (MPC) shows a superiority of the adaptive fuzzy
      integral sliding mode control with regard to two conventional methods of BGL
      regulation (PID and MPC) and sliding mode control.

PMID- 30201284
TI  - Cardiac spiral wave drifting due to spatial temperature gradients - A numerical
      study.
AB  - Cardiac rotors are believed to be a major driver source of persistent atrial
      fibrillation (AF), and their spatiotemporal characterization is essential for
      successful ablation procedures. However, electrograms guided ablation have not
      been proven to have benefit over empirical ablation thus far, and there is a
      strong need of improving the localization of cardiac arrhythmogenic targets for
      ablation. A new approach for characterize rotors is proposed that is based on
      induced spatial temperature gradients (STGs), and investigated by theoretical
      study using numerical simulations. We hypothesize that such gradients will cause
      rotor drifting due to induced spatial heterogeneity in excitability, so that
      rotors could be driven towards the ablating probe. Numerical simulations were
      conducted in single cell and 2D atrial models using AF remodeled kinetics. STGs
      were applied either linearly on the entire tissue or as a small local
      perturbation, and the major ion channel rate constants were adjusted following
      Arrhenius equation. In the AF-remodeled single cell, recovery time increased
      exponentially with decreasing temperatures, despite the marginal effect of
      temperature on the action potential duration. In 2D models, spiral waves drifted
      with drifting velocity components affected by both temperature gradient direction
      and the spiral wave rotation direction. Overall, spiral waves drifted towards the
      colder tissue region associated with global minimum of excitability. A local
      perturbation with a temperature of T = 28  degrees C was found optimal for spiral
      wave attraction for the studied conditions. This work provides a preliminary
      proof-of-concept for a potential prospective technique for rotor attraction. We
      envision that the insights from this study will be utilize in the future in the
      design of a new methodology for AF characterization and termination during
      ablation procedures.

PMID- 30201285
TI  - Acrylamides and methacrylamides as alternative monomers for dental adhesives.
AB  - OBJECTIVE: Synthesize and characterize a methacrylamide monomer for adhesive
      system and evaluate the physicochemical properties of the adhesive resin.
      METHODS: The liquid methacrylamide monomer N,N',N"-(nitrilotris(ethane-2,1
      dyil)tris(2-methylacrylamide) (TMA) was prepared by reaction of methacrylic
      anhydride and tris(2-aminoethyl)amine with 60% yields. The TMA structure was
      analyzed by 1H NMR, 13C NMR, ATR-FTIR and UHPLC-QTOF-MS. Experimental adhesive
      resin containing bisphenol-A glycidyl methacrylate (BISGMA), 2
      hydroxyethylacrylamide (HEAA), 2-hydroxyethylmethacrylate (HEMA) and TMA were
      formulated. Polymerization kinetics of neat TMA and experimental adhesive resin
      (TMA33%/HEAA66%, TMA50%/HEAA50%, TMA66%/HEAA33%, TMA50%/HEMA50%, BisGMA/HEAA/TMA
      and BisGMA/HEMA) were evaluated using Differential Scanning Calorimetry.
      Physiochemical properties for BisGMA/HEAA/TMA and BisGMA/HEMA adhesives were
      evaluated by cytotoxicity, ultimate tensile strength (UTS), softening in solvent
      (DeltaKHN), contact angle (theta), microtensile bond strength (MUTBS) and failure
      analysis. A primer was also formulated with H2O/HEAA/AMPS (2-acrylamido-2
      methylpropane sulfonic acid) and the pH value was verified and compared to
      commercial primer. RESULTS: Adhesive resin with only HEAA and TMA
      (TMA33%/HEAA66%, TMA50%/HEAA50%, TMA66%/HEAA33%) showed lower conversion and
      polymerization rate after 40s of light activation. Conversion up to 60% was found
      for BisGMA/HEAA/TMA and BisGMA/HEMA adhesive resin without significant difference
      between groups, p>0.05. Cytotoxicity, UTS, MUTBS, DeltaKHN and theta showed no
      statistical difference, p>0.05, between BisGMA/HEAA/TMA and BisGMA/HEMA adhesive
      resin. SIGNIFICANCE: In this study, the proposed synthetic route resulted in a
      tris(methacrylamide). A new primer composed without acrylates or methacrylates
      was formulated for 3-step etch-and-rinse adhesive system without the presence of
      HEMA monomer. Physicochemical properties and cell viability of BisGMA/HEAA/TMA
      adhesive resin represents an alternative adhesive resin without HEMA monomer.

PMID- 30201286
TI  - Functionalized epigallocatechin gallate copolymer inhibit dentin matrices
      degradation: Mechanical, solubilized telopeptide and proteomic assays.
AB  - OBJECTIVES: We investigated the biostability of dentin organic matrices treated
      with epigallocatechin gallate (EGCG) in comparison to chlorhexidine (CHX), both
      extracted from functionalized copolymers. METHODS: Copolymers were prepared with
      bis-GMA:TEGDMA and incorporated with 1% of EGCG or CHX (w/w). Blank copolymers
      were used as control. Copolymer samples were individually stored in 1mL deionized
      water to produce copolymer extracts. Dentin matrices were obtained by
      demineralization of dentin disks in 10% phosphoric acid solution. Matrices were
      individually treated with 1mL of the copolymer extracts or distilled water for
      48h. Collected extracts were analyzed by high-performance liquid chromatography
      (HPLC) for the presence and quantification of EGCG, CHX, and copolymer by
      products. Treated dentin matrices were tested for ultimate tensile strength,
      gravimetric changes, and swelling ratio. The treatment media were tested for
      total protein concentration, and dentin protease activity through solubilized
      telopeptide (ICTP- and CTX-ELISA) assays. The treatment media were also submitted
      to proteomic analysis. RESULTS: HPLC identified released unreacted copolymer
      species and showed higher release of CHX compared to EGCG from respective
      copolymer extracts. EGCG extract inhibited activity of dentin proteolytic enzymes
      and promoted collagen biomodification observed by the telopeptide assays and in
      the changes to dentin matrix properties. The proteomic results showed less
      collagenous peptide hits in the EGCG extract media compared to CHX, and suggest
      compound-specific dentin protein binding interactions. SIGNIFICANCE: This study
      demonstrates specific antiproteolytic effect and protein interactions of EGCG
      copolymer extract directly on dentin. This represents an advancement in dental
      materials which can impact the clinical procedures.

PMID- 30201287
TI  - Modulating pH through lysine integrated dental adhesives.
AB  - OBJECTIVES: The objective of this study was to explore the effect of lysine
      integration to dental adhesives with respect to the polymerization kinetics,
      neutralization capacities in the acidic microenvironment, dynamic mechanical
      properties, and thermal properties. MATERIALS AND METHOD: Lysine was incorporated
      into liquid resin formulations at 2.5 and 5.0wt % with additional water/ethanol
      co-solvents. The co-monomer system contained 2-hydroxyethyl-methacrylate (HEMA)
      and Bisphenol A glycerolate dimethacrylate (BisGMA) with a mass ratio of 45/55.
      The kinetics of photopolymerization, neutralization capacities, lysine-leaching,
      dynamic mechanical properties and thermal properties of the control and
      experimental adhesives were analyzed. RESULTS: The degree of conversion of the
      experimental adhesive was increased substantially at 2.5wt% lysine as compared to
      the control. The experimental polymers provided acute neutralization of the
      acidic microenvironment. Approximately half of the lysine was released from the
      polymer network within one month. Under dry conditions and physiologic
      temperatures, the incorporation of lysine did not compromise the storage modulus.
      Comparison of the thermal properties suggests that the more compact structure of
      the control adhesive inhibits movement of the polymer chains resulting in
      increased Tg. SIGNIFICANCE: Incorporating lysine in the adhesive formulations led
      to promising results regarding modulating pH, which may serve as one aspect of a
      multi-spectrum approach for enhancing the durability of composite restorations.
      The results provide insight and lay a foundation for incorporating amino acids or
      peptides into adhesive formulations for pH modulation or desired bioactivity at
      the interfacial margin between the composite and tooth.

PMID- 30201289
TI  - Role of the malonyl-CoA synthetase ACSF3 in mitochondrial metabolism.
AB  - Malonyl-CoA is a central metabolite in fatty acid biochemistry. It is the rate
      determining intermediate in fatty acid synthesis but is also an allosteric
      inhibitor of the rate-setting step in mitochondrial long-chain fatty acid
      oxidation. While these canonical cytoplasmic roles of malonyl-CoA have been well
      described, malonyl-CoA can also be generated within the mitochondrial matrix by
      an alternative pathway: the ATP-dependent ligation of malonate to Coenzyme A by
      the malonyl-CoA synthetase ACSF3. Malonate, a competitive inhibitor of succinate
      dehydrogenase of the TCA cycle, is a potent inhibitor of mitochondrial
      respiration. A major role for ACSF3 is to provide a metabolic pathway for the
      clearance of malonate by the generation of malonyl-CoA, which can then be
      decarboxylated to acetyl-CoA by malonyl-CoA decarboxylase. Additionally, ACSF3
      derived malonyl-CoA can be used to malonylate lysine residues on proteins within
      the matrix of mitochondria, possibly adding another regulatory layer to post
      translational control of mitochondrial metabolism. The discovery of ACSF3
      mediated generation of malonyl-CoA defines a new mitochondrial metabolic pathway
      and raises new questions about how the metabolic fates of this multifunctional
      metabolite intersect with mitochondrial metabolism.

PMID- 30201288
TI  - International Normalized Ratio and Mortality Risk in Acute Heart Failure and
      Nonvalvular Atrial Fibrillation Patients Receiving Vitamin K Antagonists.
AB  - INTRODUCTION AND OBJECTIVES: Heart failure patients with nonvalvular atrial
      fibrillation (NVAF) on treatment with vitamin K antagonists (VKA) often have
      suboptimal international normalized ratio (INR) values. Our aim was to evaluate
      the association between INR values at admission due to acute heart failure and
      mortality risk during follow-up. METHODS: In this observational study, we
      retrospectively assessed INR on admission in 1137 consecutive patients with acute
      heart failure and NVAF who were receiving VKA treatment. INR was categorized into
      optimal values (INR = 2-3, n = 210), subtherapeutic (INR < 2, n = 660), and
      supratherapeutic (INR > 3, n = 267). Because INR did not meet the proportional
      hazards assumption for mortality, restricted mean survival time differences were
      used to evaluate the association among INR categories and the risk of all-cause
      mortality. RESULTS: During a median [interquartile range] follow-up of 2.15 years
      [0.71-4.29], 495 (43.5%) patients died. On multivariable analysis, both patients
      with subtherapeutic and supratherapeutic INR showed higher risks of all-cause
      mortality, as evidenced by their restricted mean survival time differences at 5
      years' follow-up: -0.50; 95%CI, -0.77 to -0.23 years; P < .001; and -0.40; 95%CI,
      -0.70 to -0.11 years; P = .007, respectively, compared with INR 2-3. CONCLUSIONS:
      In acute heart failure patients on treatment with VKA for NVAF, INR values out of
      normal range at admission were independently associated with a higher long-term
      mortality risk.

PMID- 30201290
TI  - Neighborhood language isolation and depressive symptoms among elderly U.S.
      Latinos.
AB  - PURPOSE: Neighborhood segregation related to cultural factors, such as language
      use, may influence elderly Latino depression. We examined the association between
      neighborhood-level Spanish language segregation and individual depressive
      symptoms among elderly Latinos. METHODS: We linked U.S. Census language use data
      with geocoded population-based data from 1789 elderly Latinos (mean age = 70.6
      years) participating in the Sacramento Area Latino Study on Aging (1998-2008).
      Neighborhood language segregation was measured with the Index of Concentration at
      the Extremes, which demonstrates the extent to which residents are concentrated
      at extremes of deprivation and privilege. We fit two-level generalized linear
      mixed models with random intercepts for census tracts to quantify the association
      between neighborhood-level language segregation and depressive symptoms,
      adjusting for identified confounders. RESULTS: After adjusting for age, sex, and
      nativity, residents of highly segregated Spanish-speaking neighborhoods had more
      depressive symptoms than those in highly segregated English-only-speaking
      neighborhoods (beta = -4.410; 95% confidence interval [CI] = -6.851 to -1.970).
      This association was largely attenuated upon adjustment for individual-level
      education (beta = -2.119; 95% CI = -4.650 to 0.413). CONCLUSIONS: Linguistically
      segregated communities may benefit from targeted outreach given the high
      depression prevalence in these neighborhoods. Furthermore, our findings suggest
      that limited access to fundamental social protections, such as education, may
      drive the segregation-depression association among U.S. Latinos.

PMID- 30201291
TI  - Discovery of selective urokinase plasminogen activator (uPA) inhibitors as a
      potential treatment for multiple sclerosis.
AB  - We report here the design and synthesis of a novel series of benzylamines that
      are potent and selective inhibitors of uPA with promising oral availability in
      rat. Further evaluation of one representative (ZK824859) of the new structural
      class showed that this compound lowered clinical scores when dosed in either
      acute or chronic mouse EAE models, suggesting that uPA inhibitors of this type
      could be useful for the treatment of multiple sclerosis.

PMID- 30201293
TI  - Synthesis and antiproliferative activities of novel quartenary ammonium spinosyn
      derivatives.
AB  - In order to enhance the mitochondria-targeting ability of spinosad. A series of
      quartenary ammonium spinosyn derivatives was designed and synthesized. Some of
      the derivatives displayed greatly enhanced antiproliferative ability towards
      tested human cancer cell lines. The structure activity relationship study
      indicated that lipophilicity has a great influence on the antiproliferative
      effects of these derivatives. The most active compound 11d exhibited remarkably
      enhanced OXPHS inhibition and apoptosis inducing ability than spinosyn A.

PMID- 30201292
TI  - b-Annulated 1,4-dihydropyridines as Notch inhibitors.
AB  - The Notch signaling pathway is involved in cell proliferation and
      differentiation, and has been recognized as an active pathway in regenerating
      tissue and cancerous cells. Notch signaling inhibition is considered a viable
      approach to the treatment of a variety of conditions including colorectal cancer,
      pancreatic cancer, breast cancer and metastatic melanoma. The discovery that the
      b-annulated dihydropyridine FLI-06 (1) is an inhibitor of the Notch pathway with
      an EC50 ~ 2.5 MUM prompted us to screen a library of related analogs. After
      structure activity studies were conducted, racemic compound 7 was identified with
      an EC50 = 0.36 MUM. Synthesis of individual enantiomers provided (+)-7 enantiomer
      with an EC50 = 0.13 MUM, or about 20-fold the potency of 1.

PMID- 30201294
TI  - Tocopherol-loaded transfersomes: In vitro antioxidant activity and efficacy in
      skin regeneration.
AB  - Transfersomes were prepared by using different polysorbates (i.e., Tween 20, 40,
      60 and 80) and loaded with tocopherol acetate, a naturally-occurring phenolic
      compound with antioxidant activity. The vesicles showed unilamellar morphology,
      small size (~85 nm), low polydispersity index (<=0.27), and high entrapment
      efficiency, which increased as a function of the length of the Tween fatty acid
      chain (from 72% to 90%). The long-term stability of the formulations was
      evaluated by means of the TurbiscanTM technology, which indicated their good
      stability, irrespective of the Tween used. The vesicles efficiently delivered
      tocopherol to the skin, and showed biocompatibility in vitro in keratinocytes and
      fibroblasts. Regardless of the Tween used, the transfersomes were able to protect
      skin cells from the oxidative damage induced by hydrogen peroxide. Additionally,
      transfersomes promoted cell proliferation and migration, which resulted in an
      acceleration of skin wound closure. These results demonstrated that tocopherol
      loaded transfersomes bear potential as topical delivery system with antioxidant
      activity and wound healing properties.

PMID- 30201295
TI  - Myocardial beta-Catenin-BMP2 signaling promotes mesenchymal cell proliferation
      during endocardial cushion formation.
AB  - Abnormal endocardial cushion formation is a major cause of congenital heart valve
      disease, which is a common birth defect with significant morbidity and mortality.
      Although beta-catenin and BMP2 are two well-known regulators of endocardial
      cushion formation, their interaction in this process is largely unknown. Here, we
      report that deletion of beta-catenin in myocardium results in formation of
      hypoplastic endocardial cushions accompanying a decrease of mesenchymal cell
      proliferation. Loss of beta-catenin reduced Bmp2 expression in myocardium and
      SMAD signaling in cushion mesenchyme. Exogenous BMP2 recombinant proteins fully
      rescued the proliferation defect of mesenchymal cells in cultured heart explants
      from myocardial beta-catenin knockout embryos. Using a canonical WNT signaling
      reporter mouse line, we showed that cushion myocardium exhibited high WNT/beta
      catenin activities during endocardial cushion growth. Selective disruption of the
      signaling function of beta-catenin resulted in a cushion growth defect similar to
      that caused by the complete loss of beta-catenin. Together, these observations
      demonstrate that myocardial beta-catenin signaling function promotes mesenchymal
      cell proliferation and endocardial cushion expansion through inducing BMP
      signaling.

PMID- 30201297
TI  - Readmission after pancreatic resection: causes, costs and cost-effectiveness
      analysis of high versus low quality hospitals using the Nationwide Readmission
      Database.
AB  - BACKGROUND: Objectives were to determine the causes of readmission and assess the
      cost-effectiveness of high (HQ) and low quality (LQ) hospitals in performing
      pancreatic resection, by using readmission rates as the measure of quality.
      METHODS: We identified 53,572 pancreatic resection cases from National
      Readmission Database from 2010 through 2014. Hospitals were risk adjusted and
      ranked based on readmission. Top 20% HQ hospitals having the lowest readmission
      rates were compared to the bottom 20% LQ hospitals with the highest readmission
      rates. RESULTS: The 90-day readmission rate was 27.2% (HQ: 25.7%, LQ: 30.9%, p <
      0.001). Compared to LQ, HQ hospitals had lower mortality (2.1% vs 10.2%, p <
      0.001) and major complication (10.5% vs 53%, p < 0.001). Major complication
      during index operation was a major predictor of readmission (RR: 1.6, 95% CI: 1.6
      1.7, p < 0.001). The optimal cut point of hospital volume associated with low
      mortality was 70 or more cases/year. Per year of survival benefit at HQ
      hospitals, the costs were lower by $9,293 with cost-savings of $6.98
      million/year. CONCLUSION: HQ hospitals were cost-effective at performing
      pancreatic resection and achieved substantial cost-savings by avoiding major
      complications during index operation and having lower rates of readmissions.
      Hospital readmission rate is a strong marker of quality of care.

PMID- 30201296
TI  - iTRAQ-based proteomics suggests LRP6, NPY and NPY2R perturbation in the
      hippocampus involved in CSDS may induce resilience and susceptibility.
AB  - AIMS: Although decades of research have revealed numerous molecular abnormalities
      in the hippocampus associated with depression, the different mechanisms involved
      in the susceptibility and resilience of mice to chronic social defeat stress
      (CSDS)-induced depression remain poorly understand. Through the social defeat
      model, we can study the differences in molecular changes between the susceptible
      and resilient mice. MAIN METHODS: We used a proteomic-based platform to compare
      hippocampal proteins in CSDS mice with those in control mice. Differentially
      expressed proteins were identified through isobaric tags for relative and
      absolute quantitation (iTRAQ) combined with LC-MS/MS. We then analyzed the
      results by ingenuity pathway analysis (IPA) and verified five proteins by western
      blotting. KEY FINDINGS: Mice were exposed to 10 days of CSDS, which successfully
      induced stress-susceptible and -resilient phenotypes. 161 and 134 proteins were
      significantly differentially expressed in the susceptible and resilient groups,
      respectively, compared with the levels in the control group. The Rac signaling
      and the GABA receptors signaling pathways were the common top-ranking pathways.
      We found that low-density lipoprotein receptor-related protein 6 (LRP6) was
      upregulated in resilient mice and neuropeptide Y (NPY) was downregulated in
      susceptible mice compared with the levels in control mice. Moreover, neuropeptide
      Y receptor type 2 (NPY2R) protein expression in susceptible mice was
      downregulated compared with that in the resilient group. SIGNIFICANCE: Our
      findings in the three groups potentially reveal the differences in molecular
      mechanisms underlying depression between susceptible and resilient mice. The
      results provide insight into molecular abnormalities of the hippocampus in CSDS
      mice and some potential drug targets for treating depression.

PMID- 30201298
TI  - Inhibition of Lincpint expression affects insulin secretion and apoptosis in
      mouse pancreatic beta cells.
AB  - LncRNAs have been reported to maintain islet function and are associated with the
      development of diabetes. Here, we investigated Lincpint biological functions in
      mouse pancreatic beta cells both in vivo and in vitro. We observed that Lincpint
      was highly expressed in BALB/c mouse islets and downregulated in db/db mouse
      islets by using qRT-PCR. Lincpint could be regulated by different concentrations
      of glucose in MIN6 cells. MTT and flow cytometry showed that silencing Lincpint
      expression in vitro increased cell apoptosis. In a GSIS assay, we detected that
      inhibition of the expression of Lincpint suppressed insulin synthesis and
      secretion. In male BALB/c mouse, blood glucose and serum insulin were decreased
      after knockdown of Lincpint expression as detected by IPGTT and ELISA.
      Immunohistochemistry indicated that positive islet area and expression of Pdx1
      and Glut2 was reduced after Lincpint silencing in male BALB/c mouse. These
      findings suggest that Lincpint may play an important role in maintaining islet
      beta cell function and is worthy of further investigation due to its potential in
      diabetes treatment.

PMID- 30201299
TI  - Perioperative Troponin is a Predictor of Both Short- and Intermediate-term
      Mortality Among Patients Undergoing Major Urologic Surgery.
AB  - OBJECTIVE: To determine whether a positive troponin is a predictor of
      intermediate- and long-term mortality in patients undergoing major urologic
      surgeries at our institution. METHODS: This is a retrospective analysis of
      patients undergoing major urologic surgery at the Cleveland Clinic from 2010
      2015. Patients were stratified by the presence and maximum value of troponin
      blood-draw, if performed within 30 days of surgery. Survival analysis was
      performed using Kaplan-Meier function (univariate) and Cox regression analysis
      (continuous) to assess mortality risk. RESULTS: Within 30 days of surgery, 1305
      (15.5%) patients a troponin drawn, and 304 (3.6%) of them had an abnormal
      troponin level (>0.01 ng/mL). Patients with positive troponin drawn for cause
      within 30 days of surgery had a significantly decreased overall survival at 5
      years of 70.6% (95% CI 62.6, 77.2) when compared to patients with negative
      troponin (81.7% [95% CI 77.4, 85.3]) and no troponin drawn (90.4% [95% CI 89.0,
      91.6]). CONCLUSION: For cause serum troponin blood draw and peak levels
      demonstrated a positive correlation with all-cause mortality in patients
      undergoing major urologic surgeries Prospective studies are needed to better
      understand the utility of postoperative troponin as predictive marker of
      mortality.

PMID- 30201300
TI  - Efficacy of Pressure Regulating Balloon Exchange in Men With Post Artificial
      Urinary Sphincter Persistent or Recurrent Stress Urinary Incontinence.
AB  - OBJECTIVE: To assess the efficacy of exchanging the pressure regulating balloon
      (PRB) to 71-80 cm H2O in patients with persistent or recurrent stress urinary
      incontinence (SUI) following artificial urinary sphincter (AUS) placement.
      METHODS: Patients with SUI following AUS placement who underwent PRB replacement
      between 2011 and 2017 in the absence of urethral cuff malfunction, atrophy,
      stricture, or erosion were reviewed. Primary outcomes included changes in pad per
      day (PPD), Incontinence Symptom Index score, and Incontinence Quality of Life (I
      QOL). Secondary outcomes included rates of device erosion and all-cause explant
      or revision. Differences were compared between patients with and without erosion,
      explant, or revision. Kaplan Meier device survival analysis was performed.
      RESULTS: Twenty two patients (67 +/- 9 years, body mass index of 30 +/- 5 kg/m2)
      with a median follow up of 22.4 months (IQR 9.3, 47.3) were included.
      Incontinence etiology included radical prostatectomy in 60% of patients. After
      PRB exchange, the average number of PPD decreased from 4.0 +/- 3.0 to 1.0 +/- 1.6
      PPD (P = .01), as did Incontinence Symptom Index scores (21.6 +/- 8.5 vs 16.3 +/-
      8.1, P <.001) and Incontinence Quality of Life (15.2 +/- 6.8 vs 7.2 +/- 3.4, P =
      .01). Three patients with prior radiation (14%) experienced cuff erosion. The
      explantation/revision rate was 45%(10/22) at 33.5(IQR 8.9,48) months. Kaplan
      Meier analysis demonstrated 68%(15/22) and 41%(9/22) retained their device for 12
      and 24 months, respectively. CONCLUSION: PRB exchange can transiently alleviate
      persistent or recurrent post-AUS SUI in the absence of mechanical failure or
      urethral pathology. Caution is warranted in patients with prior radiation as this
      was a risk factor for urethral erosion. Although many patients may require device
      revision within 2 years, it can be a temporizing solution that avoids urethral
      manipulation and periprocedural device deactivation.

PMID- 30201301
TI  - Diagnostic Accuracy of a Rapid Biparametric MRI Protocol for Detection of
      Histologically Proven Prostate Cancer.
AB  - OBJECTIVE: To evaluate the performance of a rapid, low cost, noncontrast MRI
      examination as a secondary screening tool in detection of clinically significant
      prostate cancer. METHODS: In this prospective single institution study, 129
      patients with elevated prostate-specific antigen levels or abnormal digital
      rectal examination findings underwent MRI with an abbreviated biparamatric MRI
      protocol consisting of high-resolution axial T2- and diffusion-weighted images.
      Index lesions were classified according to modified Prostate Imaging - Reporting
      and Data System (mPI-RADS) version 2.0. All patients underwent standard
      transrectal ultrasound-guided biopsy after MRI with the urologist being blinded
      to MRI results. Subsequently, all patients with suspicious lesions (mPI-RADS 3,
      4, or 5) underwent cognitively guided targeted biopsy after discussion of MRI
      results with the urologist. Sensitivity and negative predictive value for
      identification of clinically significant prostate cancer (Gleason score 3+4 and
      above) were determined. RESULTS: Rapid biparametric MRI discovered 176 lesions
      identified in 129 patients. Rapid MRI detected clinically significant cancers
      with a sensitivity of 95.1% with a negative predictive value of 95.1% and
      positive predictive value of 53.2%, leading to a change in management in 10.8% of
      the patients. False negative rate of biparametric (bp) MRI was 4.7%. CONCLUSION:
      We found that a bp-MRI examination can detect clinically significant lesions and
      changed patient management in 10.8% of the patients. A rapid MRI protocol can be
      used as a useful secondary screening tool in men presenting with suspicion of
      prostate cancer.

PMID- 30201302
TI  - TMPRSS2:ERG gene fusion expression regulates bone markers and enhances the
      osteoblastic phenotype of prostate cancer bone metastases.
AB  - Prostate cancers have a strong propensity to metastasize to bone and promote
      osteoblastic lesions. TMPRSS2:ERG is the most frequent gene rearrangement
      identified in prostate cancer, but whether it is involved in prostate cancer bone
      metastases is largely unknown. We exploited an intratibial metastasis model to
      address this issue and we found that ectopic expression of the TMPRSS2:ERG fusion
      enhances the ability of prostate cancer cell lines to induce osteoblastic lesions
      by stimulating bone formation and inhibiting the osteolytic response. In line
      with these in vivo results, we demonstrate that the TMPRSS2:ERG fusion protein
      increases the expression of osteoblastic markers, including Collagen Type I Alpha
      1 Chain and Alkaline Phosphatase, as well as Endothelin-1, a protein with a
      documented role in osteoblastic bone lesion formation. Moreover, we determined
      that the TMPRSS2:ERG fusion protein is bound to the regulatory regions of these
      genes in prostate cancer cell lines, and we report that the expression levels of
      these osteoblastic markers are correlated with the expression of the TMPRSS2:ERG
      fusion in patient metastasis samples. Taken together, our results reveal that the
      TMPRSS2:ERG gene fusion is involved in osteoblastic lesion formation induced by
      prostate cancer cells.

PMID- 30201303
TI  - Enhanced protective immunity against spring viremia of carp virus infection can
      be induced by recombinant subunit vaccine conjugated to single-walled carbon
      nanotubes.
AB  - As a successful prevention strategy for controlling the highly contagious and
      pathogenic disease of spring viremia of carp (SVC), DNA vaccines reported in
      recent years could trigger protective responses against SVC with the means of
      injection. However, there remains many concerns and uncertainties related to DNA
      vaccination as well as injection is labor intensive, costly and not suitable to
      vaccinate large numbers of fish. Therefore, more efficient and safe prophylactic
      measures should be urgently investigated. In this research, single-walled carbon
      nanotubes (SWCNTs) as the candidate SWCNTs-pET32a-G subunit vaccine carrier were
      administrated via bath (1, 5, 10, 20, 40 mg L-1) or injection (1, 4, 8, 12, 20
      MUg) in common carp juvenile, and the different immune treatments to induce
      immunoprotective effect were analyzed. The results showed that SWCNTs-pET32a-G
      could enter fish body after immersion for 10 h, furthermore, compared to control
      groups, antibody levels, the non-specific immune parameters (complement activity,
      superoxide dismutase activity and alkaline phosphatase activity), and immune
      related genes (especially the TNF-alpha and IFNg2b) in vaccinated groups were
      significantly enhanced in fish immunized with SWCNTs-subunit vaccine. In
      addition, as a promising carrier, SWCNTs can increase the immune protective
      effect of naked subunit vaccine by ca. 16% in bath immunization group and by ca.
      23% in injection group. This study suggests that SWCNTs-vaccine may represent a
      potentially efficient immersion vaccine against viral pathogens of fish in the
      future.

PMID- 30201304
TI  - Examining determinants for reporting suspected adverse events following HPV
      vaccination in Denmark.
AB  - HPV vaccination has been offered to 12-year-old girls as part of the Danish
      Childhood Vaccination Programme since 2009. From 2013, an increasing number of
      suspected severe adverse events (AE) without a documented causal link to the
      vaccine was observed, resulting in public concerns about vaccine safety and a
      decline in uptake. This study aimed at describing the group of females reporting
      AE and comparing them to vaccinated peers not reporting AE. A questionnaire
      focusing on demographics, lifestyle, and health-related issues was distributed to
      251 female cases who had reported severe AE and 1,003 female controls randomly
      selected from the population-based Danish Vaccination Registry. All had been HPV
      vaccinated. There were no significant differences on measures of self-reported
      psychiatric or somatic conditions before vaccination. More cases reported being
      physically very active prior to first HPV vaccination (OR 4.2) whereas fewer
      cases than controls sometimes (OR 0.31) or often/always (OR 0.36) felt sad. This
      is unexpected because two recent Danish registry-based case-control studies
      concluded that females reporting severe AE were more likely to consult a
      psychologist/psychiatrist and to have pre-existing psychiatric conditions before
      first HPV vaccination. One of these studies also showed that cases had increased
      health-care seeking regarding a number of somatic conditions prior to first
      vaccination. Our study adds value when seeking to understand the lifeworld of the
      affected females and their interpretations of their everyday lives pre- and post
      HPV vaccination.

PMID- 30201305
TI  - Strategies to increase vaccine acceptance and uptake: From behavioral insights to
      context-specific, culturally-appropriate, evidence-based communications and
      interventions.

PMID- 30201306
TI  - De novo transcriptome assembly of the coral Agaricia lamarcki (Lamarck's sheet
      coral) from mesophotic depth in southwest Puerto Rico.
AB  - The plating coral, Agaricia lamarcki is a widely distributed species inhabiting
      reefs across the Caribbean basin and Florida. This species is of interest since
      it is considered a depth-generalist, found from 10 to 70 m. Given the scope of
      contemporary studies on this coral's population dynamics and physiology, as well
      as, the potential of mesophotic reefs to be refuge habitats for deteriorated
      shallow water reefs, we present the first de novo transcriptome assembly of an
      important mesophotic coral. Using next-generation paired-end sequencing (Illumina
      Hiseq4000; 2 * 150 bp), we obtained a total of 82,506,058 raw reads. The novel
      transcriptome assembly strategy included the recently developed National Center
      for Genome Analysis Support de novo transcriptome assembly pipeline. Assembly
      produced a total of 101,322 biologically true, non-redundant transcripts with an
      average contig length of 959 and N50 of 1830. EvidentialGene and TransDecoder
      were used to identify open reading frames (ORFs) with homology insight provided
      by the UniProtKb and PFAM databases. ORF prediction resulted in 38,517 putative
      ORFs of which 12,107 ORFs were annotated as genes dealing with molecular
      function, 1266 with biological processes and 416 with cellular components.

PMID- 30201307
TI  - Dynamic expression of p75NTR and Lingo-1 during development of mouse retinofugal
      pathway.
AB  - Our previous studies showed interaction of Nogo at the midline with its receptor
      (NgR) on optic axons plays a role in axon divergence at the mouse optic chiasm.
      Since NgR lacks a cytoplasmic domain, it needs transmembrane receptor partners
      for signal transduction. In this study, we examined whether the co-receptors of
      NgR, low-affinity neurotrophic receptor (p75NTR) and Lingo-1, are localized on
      axons in the mouse optic pathway. In the retina, p75NTR and Lingo-1 were observed
      on neuroepithelial cells at E13 and later on the retinal ganglion cells at E14
      and E15. At the optic disc, p75NTR was observed on the retinal axons, whereas
      Lingo-1 was found on glial processes surrounding the axon fascicles. Both p75NTR
      and Lingo-1 were found on axons in the optic stalk, optic chiasm and optic tract.
      Furthermore, a transient expression of Lingo-1 was observed on the SSEA-1
      positive chiasmatic neurons at E13, but not at later developmental stages. The
      presence of p75NTR and Lingo-1 on optic axons provides further supports to the
      contribution of Nogo/NgR signaling in axon divergence at the mouse optic chiasm.

PMID- 30201308
TI  - Possible involvement of the peripheral Mu-opioid system in antinociception
      induced by bergamot essential oil to allodynia after peripheral nerve injury.
AB  - The essential oil of bergamot (BEO) is one of the most common essential oils and
      is most familiar to the general public. The aims of this study were to
      investigate the effect of intraplantar (i.pl.) BEO on neuropathic allodynia
      induced by partial sciatic nerve ligation (PSNL) in mice and the opioid receptor
      subtypes involved in the antiallodynic effects of BEO. Our findings showed that a
      single dose of i.pl. administration of BEO significantly inhibited the PSNL
      induced neuropathic pain using the von Frey test. The i.pl pretreatment with
      naloxone methiodide, a peripherally acting MU-opioid receptor preferring
      antagonist, beta-funaltrexamine hydrochloride (beta-FNA), a selective MU-opioid
      receptor antagonist, and beta-endorphin antiserum significantly reversed the
      antiallodynic effect of BEO in the von Frey test, but not by naltrindole, the
      nonselective delta-opioid receptor antagonist and nor-binaltorphimine, the
      selective kappa-opioid receptor antagonist. Furthermore, in the western blotting
      analysis, i.pl. administration of BEO resulted in a significant blockage of
      spinal extracellular signal-regulated protein kinase (ERK) activation induced by
      PSNL. Naloxone methiodide and beta-FNA significantly reversed the blockage of
      spinal ERK activation induced by BEO. These results suggest that i.pl. injection
      of BEO-induced antiallodynic effect and blockage of spinal ERK activation may be
      triggered by activation of peripheral MU-opioid receptors.

PMID- 30201309
TI  - A gain-of-function study of amelioration of pentylenetetrazole-induced seizures
      by endogenous prostaglandin D2.
AB  - We previously showed that knockout mice of hematopoietic prostaglandin (PG) D
      synthase (H-PGDS) produce less PGD2 to exacerbate pentylenetetrazole (PTZ)
      induced seizures. Here, we adopted a gain-of-function strategy and used
      transgenic mice that over-express human H-PGDS enzyme, to elucidate the role of
      overproduction of endogenous PGD2 in PTZ-induced seizures. H-PGDS-transgenic mice
      showed the elevated level of a urinary metabolite of PGD2, tetranor-PGDM, 3.3-
      and 2.8-fold higher than the wild-type littermates under the basal condition and
      after the PTZ administration, respectively, without significantly changing the
      urinary concentration of a PGE2-metabolite, tetranor-PGE2. The intensity of PTZ
      induced seizures was decreased in H-PGDS-transgenic mice as evident by the
      increased seizure onset latency, and a decrease in total duration of generalized
      tonic-clonic seizures and a total number of EEG seizure spikes during the
      postictal period (84 s, 17 s, and 5.3/min, respectively), as compared to wild
      type mice (53 s, 24 s, and 12.6/min, respectively). These results indicate that
      overproduction of endogenous PGD2 decreased PTZ-induces seizures.

PMID- 30201310
TI  - The value of Coronary Artery computed Tomography as the first-line anatomical
      test for stable patients with indications for invasive angiography due to
      suspected Coronary Artery Disease: CAT-CAD randomized trial.
AB  - BACKGROUND: The aim of this prospective, randomized trial was to evaluate whether
      the use of coronary computed tomography angiography (CCTA) as the first-line
      anatomical test in patients with suspected significant coronary artery disease
      (CAD) may reduce the number of coronary invasive angiographies (ICA), and expand
      the use of CCTA in patients currently diagnosed invasively. METHODS: 120 patients
      (age:60.6 +/- 7.9 years, 35% female) with indications to ICA were randomized 1:1
      to undergo CCTA versus direct ICA. Outcomes were evaluated during the diagnostic
      and therapeutic periods. RESULTS: The number of invasively examined patients was
      reduced by 64.4% in the CCTA group as compared to the direct ICA group (21vs59,p
      < 0.0001). The number of patients with ICAs not followed by coronary intervention
      was reduced by 88.1% with the CCTA strategy (5vs42,p < 0.0001). Over the
      diagnostic and therapeutic course there were no significant differences regarding
      the median volume of contrast (CCTA 80.3 ml[65.0-165.0] vs ICA 90.0 ml[55.0
      100.0], p = 0.099), while a non-significant trend towards higher radiation dose
      in the CCTA group was observed (9.9 mSv[7.0-22.1] vs 9.4 mSv[5.2-14.0], p =
      0.05). There were no acute cardiovascular events. CONCLUSIONS: CCTA may
      hypothetically act as an effective 'gatekeeper' to the catheterization laboratory
      in the diagnosis of stable patients with current indications for ICA. This
      strategy may result in non-invasive, outpatient-based triage of two thirds of
      individuals without actionable CAD, obviating unnecessary invasive examinations.
      However, the longer follow-up is indispensable. CLINICALTRIALS. GOV NUMBER:
      NCT02591992.

PMID- 30201311
TI  - Time- and sex-dependent efficacy of magnesium sulfate to prevent behavioral
      impairments and cerebral damage in a mouse model of cerebral palsy.
AB  - Cerebral lesions acquired in the perinatal period can induce cerebral palsy (CP),
      a multifactorial pathology leading to lifelong motor and cognitive deficits.
      Several risk factors, including perinatal hypoxia-ischemia (HI), can contribute
      to the emergence of CP in preterm infants. Currently, there is no international
      consensus on treatment strategies to reduce the risk of developing CP. A meta
      analysis showed that magnesium sulfate (MgSO4) administration to mothers at risk
      of preterm delivery reduces the risk of developing CP (Crowther et al., 2017).
      However, only a few studies have investigated the long-term effects of MgSO4 and
      it is not known whether sex would influence MgSO4 efficacy. In addition, the
      search for potential deleterious effects is essential to enable broad use of
      MgSO4 in maternity wards. We used a mouse model of perinatal HI to study MgSO4
      effects until adolescence, focusing on cognitive and motor functions, and on some
      apoptosis and inflammation markers. Perinatal HI at postnatal day 5 (P(5))
      induced (1) sensorimotor deficits in pups; (2) increase in caspase-3 activity 24
      h after injury; (3) production of proinflammatory cytokines from 6 h to 5 days
      after injury; (4) behavioral and histological alterations in adolescent mice with
      considerable interindividual variability. MgSO4 prevented sensorimotor
      alterations in pups, with the same efficacy in males and females. MgSO4 displayed
      anti-apoptotic and anti-inflammatory effects without deleterious side effects.
      Perinatal HI led to motor coordination impairments in female adolescent mice and
      cognitive deficits in both sexes. MgSO4 tended to prevent these motor and
      cognitive deficits only in females, while it prevented global brain tissue damage
      in both sexes. Moreover, interindividual and intersexual differences appeared
      regarding the lesion size and neuroprotection by MgSO4 in a region-specific
      manner. These differences, the partial prevention of disorders, as well as the
      mismatch between histological and behavioral observations mimic clinical
      observations. This underlines that this perinatal HI model is suitable to further
      analyze the mechanisms of sex-dependent perinatal lesion susceptibility and MgSO4
      efficacy.

PMID- 30201312
TI  - UPR activation specifically modulates glutamate neurotransmission in the
      cerebellum of a mouse model of autism.
AB  - An increasing number of rare mutations linked to autism spectrum disorders have
      been reported in genes encoding for proteins involved in synapse formation and
      maintenance, such as the post-synaptic cell adhesion proteins neuroligins. Most
      of the autism-linked mutations in the neuroligin genes map on the extracellular
      protein domain. The autism-linked substitution R451C in Neuroligin3 (NLGN3)
      induces a local misfolding of the extracellular domain, causing defective
      trafficking and retention of the mutant protein in the endoplasmic reticulum
      (ER). The activation of the unfolded protein response (UPR), due to misfolded
      proteins accumulating in the ER, has been implicated in pathological and
      physiological conditions of the nervous system. It was previously shown that the
      over-expression of R451C NLGN3 in a cellular system leads to the activation of
      the UPR. Here, we have investigated whether this protective cellular response is
      detectable in the knock-in mouse model of autism endogenously expressing R451C
      NLGN3. Our data showed up-regulation of UPR markers uniquely in the cerebellum of
      the R451C mice compared to WT littermates, at both embryonic and adult stages,
      but not in other brain regions. Miniature excitatory currents in the Purkinje
      cells of the R451C mice showed higher frequency than in the WT, which was rescued
      inhibiting the PERK branch of UPR. Taken together, our data indicate that the
      R451C mutation in neuroligin3 elicits UPR in vivo, which appears to trigger
      alterations of synaptic function in the cerebellum of a mouse model expressing
      the R451C autism-linked mutation.

PMID- 30201313
TI  - NMR Methods of Characterizing Biomolecular Structural Dynamics and Conformational
      Ensembles.

PMID- 30201314
TI  - Multiobjective strain design: A framework for modular cell engineering.
AB  - Diversity of cellular metabolism can be harnessed to produce a large space of
      molecules. However, development of optimal strains with high product titers,
      rates, and yields required for industrial production is laborious and expensive.
      To accelerate the strain engineering process, we have recently introduced a
      modular cell design concept that enables rapid generation of optimal production
      strains by systematically assembling a modular cell with an exchangeable
      production module(s) to produce target molecules efficiently. In this study, we
      formulated the modular cell design concept as a general multiobjective
      optimization problem with flexible design objectives derived from mass balance.
      We developed algorithms and an associated software package, named ModCell2, to
      implement the design. We demonstrated that ModCell2 can systematically identify
      genetic modifications to design modular cells that can couple with a variety of
      production modules and exhibit a minimal tradeoff among modularity, performance,
      and robustness. Analysis of the modular cell designs revealed both intuitive and
      complex metabolic architectures enabling modular production of these molecules.
      We envision ModCell2 provides a powerful tool to guide modular cell engineering
      and sheds light on modular design principles of biological systems.

PMID- 30201315
TI  - Association between changes in platelet reactivity during elective percutaneous
      coronary intervention and periprocedural myocardial infarction: A pilot study.
AB  - BACKGROUND: High platelet reactivity before percutaneous coronary intervention
      (PCI) reportedly increases the risk of PCI-related myocardial infarction (PMI)
      following elective PCI. We conducted a pilot study to evaluate changes in
      platelet reactivity during PCI and their association with the incidence of PMI.
      METHODS: In total, 133 consecutive patients undergoing elective PCI after
      pretreatment with dual antiplatelet therapy for at least 7 days were
      prospectively enrolled. Platelet reactivity was measured by the VerifyNow(r)
      assay (International Technidyne Corporation, Edison, NJ, USA) immediately before
      and after PCI. RESULTS: Platelet reactivity significantly increased from 177.3 +/
      53.4 P2Y12 reaction units (PRU) before PCI to 203.4 +/- 52.8 PRU immediately
      after PCI (p < 0.001). Absolute changes in platelet reactivity were significantly
      greater in patients with than without PMI (32.4 +/- 29.0 vs. 21.2 +/- 24.8 PRU,
      respectively; p = 0.021). In the multivariable logistic regression analysis, the
      absolute change in PRU was an independent predictor of the incidence of PMI.
      Receiver operating characteristic curve analysis of the change in PRU during PCI
      for discriminating PMI showed a sensitivity, specificity, and the cut-off value
      of 46%, 76%, and 37 PRU, respectively (area under the curve = 0.607, p = 0.0235).
      When the patients were divided into two groups, namely a greater (change in PRU
      >= 37) and smaller (change in PRU < 37) increase group, the incidence rate of PMI
      was significantly higher in the greater than smaller increase group (59.1% vs.
      34.8%, respectively; p = 0.008). Additional exploratory analyses by intracoronary
      imaging demonstrated that the proximal reference lumen area in the greater
      increase group was significantly smaller than that in the smaller increase group
      (6.5 +/- 2.4 vs. 7.7 +/- 3.1 mm2, respectively; p = 0.032). CONCLUSION: An
      increase in platelet reactivity after elective PCI is possibly associated with
      PMI. This finding should be validated by a larger-scale study.

PMID- 30201316
TI  - Hypertension and chronic inhibition of endocannabinoid degradation modify the
      endocannabinoid system and redox balance in rat heart and plasma.
AB  - The interaction between the endocannabinoid and ROS signaling systems has been
      demonstrated in different organs. Inhibitors of fatty acid amide hydrolase
      (FAAH), the key enzyme responsible for degradation of the endocannabinoid
      anandamide, are postulated to possess anti-hypertensive potential. Here, we
      compared the effects of hypertension and chronic FAAH inhibition by URB597 on the
      endocannabinoid system and redox balance in spontaneously hypertensive rats (SHR)
      and hypertensive deoxycorticosterone acetate (DOCA)-salt rats. Enhanced oxidative
      stress and lipid peroxidation were found in both hypertension models.
      Hypertension affected cardiac and plasma endocannabinoid systems in a model
      dependent manner: anandamide and 2-arachidonoylglycerol levels decreased in SHR
      and increased in DOCA-salt. Cardiac CB1 receptor expression increased in both
      models while higher CB2 receptor expression was only in DOCA-salt. URB597
      increased endocannabinoid levels in both models but produced the partial
      reduction of oxidative stress in DOCA-salt but not in SHR. Notably, URB597
      decreased antioxidant defense and increased lipid peroxidation products in
      normotension. Therefore, the therapeutic potential of FAAH inhibitors should be
      interpreted cautiously.

PMID- 30201317
TI  - Glottic patency during noninvasive ventilation in patients with chronic
      obstructive pulmonary disease.

PMID- 30201318
TI  - Improved accuracy in the assessment of vertebral cortical thickness by
      quantitative computed tomography using the Iterative Convolution OptimizatioN
      (ICON) method.
AB  - Vertebral whole bone strength is substantially affected by cortical bone
      properties. Disease and therapy may affect cancellous and cortical bone
      differently. Unlike Dual X-ray Absorptiometry (DXA), Quantitative Computed
      Tomography (QCT) permits selective assessment of cortical and cancellous bone,
      but image quality limits the accuracy. We present an image processing method
      specifically adopted to thin cortices that substantially improves accuracy. Ten
      human vertebrae embedded in epoxy resin were imaged using clinical QCT and High
      Resolution QCT (HR-QCT) protocols, both acquired on a clinical whole body CT
      scanner, whereas high resolution peripheral QCT (HR-pQCT) was used as gold
      standard. Microstructural variables and BMD were calculated using in-house
      software StructuralInsight for QCT and HR-QCT and the manufacturer's MUCT
      evaluation software for HR-pQCT. An adjusted measure, a deconvolved cortical
      thickness (dcCt.Th), corrected for partial volume effects, was derived applying
      the new Iterative Convolution OptimizatioN (ICON) method. Direct measurements of
      cortical thickness (Ct.Th) showed substantial overestimation with mean +/-
      standard deviation of 1.8 +/- 0.5 mm for QCT and 1.5 +/- 0.3 mm for HR-QCT
      compared to 0.37 +/- 0.07 mm using HR-pQCT. Correlations of both QCT (r2 = 0.05,
      p > 0.5.) and HR-QCT (r2 = 0.38, p = 0.060) with the gold standard HR-pQCT were
      not significant. Also QCT-based BMD and BMC as well as HR-QCT-based BMD did not
      show a significant correlation with the gold standard approach. Only HR-QCT-based
      BMC showed a modest correlation (r2 = 0.59, p = 0.01) After applying ICON
      corrections, dcCt.Th resulted in 0.52 +/- 0.09 mm for QCT and 0.43 +/- 0.07 mm
      for HR-QCT, both significantly correlated to HR-pQCT (r2 = 0.75, p = 0.0012 and
      r2 = 0.93, p < 0.0001, respectively). The average overestimation bias of Ct.Th
      was reduced from (402 +/- 157)% to (45 +/- 17)% for QCT and from (330 +/- 69)% to
      (19 +/- 8)% for HR-QCT. Due to inaccurate segmentation uncorrected QCT-based
      Ct.Th measures as well as BMD and BMC showed no correlation to HR-pQCT and thus
      such bias cortical data can be misleading. The application of ICON reduced random
      overestimation bias to about 50 MUm and 20 MUm for QCT and HR-QCT, respectively,
      leading to a recovery of a significant correlation with the reference data of HR
      pQCT. This reveals the potential for fairly accurate assessment of cortical
      thickness, allowing to better characterize cortical mechanical competence. These
      results warrant testing of the performance in vivo.

PMID- 30201319
TI  - Enantioselective resolution of 2-arylpropionic acid derivatives employing
      immobilization of lipase from Bacillus subtilis strain Kakrayal_1 (BSK-L).
AB  - This work studied the enantioselective resolution of 2-arylpropionic acid
      derivatives employing immobilization of lipase produced by Bacillus subtilis
      strain Kakrayal_1 (BSK-L). The efficient immobilization of lipase on modified
      silica gel was confirmed by Fourier transform infrared spectroscopy. Tethering of
      lipase facilitated the enhancement of physiochemical properties and stability of
      enzyme. Covalently immobilized enzyme retained 85% of residual activity even on
      reuse after 10th reaction cycle. Validation of immobilized lipase for
      enantioselective resolution of 2-arylpropionic acid derivatives led to 47.8%
      conversion efficiency with 87% enantiomeric excess (ee) for ketoprofen, and 27.3%
      conversion efficiency with 75% ee for flurbiprofen. The enantioselective
      resolution using immobilized lipase (BSK-L) was superior to free and commercially
      procured lipase, which suggest a potential application of immobilized lipase in
      the pharmaceutical/chemical industry.

PMID- 30201320
TI  - Valorization of polyhydroxyalkanoates production process by co-synthesis of value
      added products.
AB  - Polyhydroxyalkanoates (PHAs) are the only polyesters that are completely
      synthesized biologically and possess features equivalent to petroleum-based
      plastics besides being biodegradable. PHA based materials may certainly prove
      helpful in addressing the concerns caused due to the indiscriminate use of
      synthetic plastics. However, the cost of producing these polymers on a large
      scale is still uneconomical. Various approaches have been developed to tackle
      this issue through usage of agro-industrial wastes, co-production of high market
      value products, polymer extraction using green solvents, etc. The advent of
      recombineering and CRISPR technologies has broadened the scope of constructing a
      microbe capable of synthesizing multiple products with economic feasibility.
      Quite a few high-market value chemicals are possible to synthesize along with the
      favorable accumulation of PHA. The present article attempts to review all PHA
      polymer co-production processes with other chemicals reported till date and
      discusses the opportunities for their large-scale operation in future.

PMID- 30201321
TI  - Evaluation and optimization of anammox baffled reactor (AnBR) by artificial
      neural network modeling and economic analysis.
AB  - Anammox baffled reactor (AnBR) had a moderate start-up period of 53 days.
      Interestingly, tangled relationships between key parameters affecting anammox
      performance were observed, i.e., polynomial function for nitrogen loading rate
      (NLR) with extracellular polymeric substances (EPS), linear relationships between
      EPS with granules diameter, granules diameter with settling velocity, and
      settling velocity with biomass concentration. The correlation coefficients (R2)
      were 0.97, 0.84, 0.86, and 0.88, respectively. Furthermore, a multi-layered feed
      forward artificial neural network (ANN) was utilized for simulating and
      predicting the performance of AnBR. An ANN structure of two hidden layers with
      four neurons at 1st layer and eight neurons at 2nd layer achieved the best
      goodness of fit with the minimum mean squared error (MSE) and maximum R2 of 0.002
      and 0.99, respectively. Additionally, economic assessment stated that using AnBR
      at NLR of 4.04 +/- 0.10 kg-N/m3/day achieved the maximum net present value of
      $48100.9.

PMID- 30201322
TI  - Aerobic granular sludge: Cultivation parameters and removal mechanisms.
AB  - Aerobic granular sludge (AGS) has been the focus of many investigations, and the
      main parameters responsible for AGS formation are hydrodynamic shear force, short
      periods and feast-famine cycles. However, some other parameters are associated
      with AGS maintenance after long periods of operation. This review evaluates the
      parameters responsible for AGS formation and maintenance and some reference
      values are proposed. In addition, some discussions are addressed about the main
      metabolic pathways that AGS uses for the removal of some compounds, such as
      nutrients, organic matter, dyes, recalcitrant compounds, among others. Finally,
      the main microbial groups present in the AGS and their respective functions are
      discussed. It is also highlighted that many parameters that are taken as
      reference currently for AGS cultivation and maintenance can be optimized for
      energy savings, implementation costs, among others, as well as a greater recovery
      of resources during wastewater treatment, within the scope of the biorefinery
      concept.

PMID- 30201324
TI  - [Effect of two different doses of dexmedetomidine on the incidence of emergence
      agitation after strabismus surgery: a randomized clinical trial].
AB  - BACKGROUND AND OBJECTIVE: Emergence agitation is a postoperative negative
      behavior that affects mainly children. We studied the effect of two different
      doses of dexmedetomidine on the incidence and degree of EA in children undergoing
      strabismus surgery. METHODS: 90 patients were allocated into three equal groups;
      patients received 0.5MUg.kg-1 of dexmedetomidine in high Dex group, 0.25MUg.kg-1
      of dexmedetomidine in low Dex group, or normal saline in the placebo group. All
      drugs were received with the closure of the conjunctiva before the end of the
      surgery. Pediatric Anesthesia Emergence Delirium (PAED) scale was used to
      evaluate the agitation, and Face, Legs, Activity, Cry, Consolability (FLACC)
      scale was used for pain assessment. Adverse effects of dexmedetomidine and
      recovery times were recorded. RESULTS: The incidence of agitation was
      significantly lower in high Dex group compared to other groups and it was
      significantly lower in low Dex group compared to placebo group. The median
      (range) of FLACC score was significantly lower in both Dex groups compared to
      placebo group. Recovery times; time from removal of laryngeal mask to eye opening
      and time stay in post anesthesia care unit was significantly longer in high Dex
      group compared to other groups. No significant bradycardia or hypotension was
      recorded. Recovery time was significantly longer in high Dex group compared to
      the other two groups. CONCLUSION: Dexmedetomidine (0.5MUg.kg-1) before emergence
      from general anesthesia resulted in a reduction in the incidence of emergence
      agitation compared to a dexmedetomidine (0.25MUg.kg-1) but on the expense of
      recovery times without adverse effects.

PMID- 30201323
TI  - [The chondrotoxic and apoptotic effects of levobupivacaine and bupivacaine on the
      rabbit knee joint].
AB  - BACKGROUND: A single dose injection or continuous infusion of local anesthetics
      into the joint space is considered to be a well-defined analgesia technique. The
      aim of this study was to investigate the chondrotoxic and apoptotic effects of
      single-dose intra-articular injection of levobupivacaine and bupivacaine on
      rabbit knee joint tissues. MATERIALS AND METHODS: The animals were allocated into
      two groups each containing 20 rabbits. 0.5% levobupivacaine (Group L) and 0.5%
      bupivacaine (Group B) were applied intra-articularly to the left posterior joints
      of rabbits. At the same time, normal saline was applied to the right posterior
      leg knee joints of rabbits in both groups and used as a control (Group S). At the
      end of the 7th and 28th days after the intraarticular injections, ten randomly
      chosen rabbits in each group were killed by applying intraperitoneal thiopental.
      Sections of cartilage tissue samples were stained for light microscopic
      examinations and the TUNEL method was used to investigate apoptotic cells.
      RESULTS: As a result of immunofluorescence microscopic examination, the number of
      apoptotic cells in Group B at day 7 and day 28 were both significantly higher
      than Group L and S (p<0.05). Also, the number of apoptotic cells in Group L at
      day 7 and day 28 were both significantly higher than Group S (p<0.05).
      CONCLUSIONS: We found that bupivacaine is more chondrotoxic than other anesthetic
      agent and increases the number of apoptotic cells. These results indicated that
      bupivacaine caused high chondrotoxic damage and it led to more apoptotic
      activation than levobupivacaine.

PMID- 30201325
TI  - A survey on computer-assisted Parkinson's Disease diagnosis.
AB  - BACKGROUND AND OBJECTIVE: In this work, we present a systematic review concerning
      the recent enabling technologies as a tool to the diagnosis, treatment and better
      quality of life of patients diagnosed with Parkinson's Disease (PD), as well as
      an analysis of future trends on new approaches to this end. METHODS: In this
      review, we compile a number of works published at some well-established
      databases, such as Science Direct, IEEEXplore, PubMed, Plos One,
      Multidisciplinary Digital Publishing Institute (MDPI), Association for Computing
      Machinery (ACM), Springer and Hindawi Publishing Corporation. Each selected work
      has been carefully analyzed in order to identify its objective, methodology and
      results. RESULTS: The review showed the majority of works make use of signal
      based data, which are often acquired by means of sensors. Also, we have observed
      the increasing number of works that employ virtual reality and e-health
      monitoring systems to increase the life quality of PD patients. Despite the
      different approaches found in the literature, almost all of them make use of some
      sort of machine learning mechanism to aid the automatic PD diagnosis.
      CONCLUSIONS: The main focus of this survey is to consider computer-assisted
      diagnosis, and how effective they can be when handling the problem of PD
      identification. Also, the main contribution of this review is to consider very
      recent works only, mainly from 2015 and 2016.

PMID- 30201326
TI  - A bone mineralization defect in the Pahenu2 model of classical phenylketonuria
      involves compromised mesenchymal stem cell differentiation.
AB  - Osteopenia is observed in some patients affected by phenylalanine hydroxylase
      (PAH) deficient phenylketonuria (PKU). Bone density studies, in diverse PKU
      patient cohorts, have demonstrated bone disease is neither fully penetrant nor
      uniform in bone density loss. Biochemical assessment has generated a muddled
      perspective regarding mechanisms of the PKU bone phenotype where the
      participation of hyperphenylalaninemia remains unresolved. Osteopenia is realized
      in the Pahenu2 mouse model of classical PKU; although, characterization is
      incomplete. We characterized the Pahenu2 bone phenotype and assessed the effect
      of hyperphenylalaninemia on bone differentiation. Employing Pahenu2 and control
      animals, cytology, static and dynamic histomorphometry, and biochemistry were
      applied to further characterize the bone phenotype. These investigations
      demonstrate Pahenu2 bone density is decreased 33% relative to C57BL/6; bone
      volume/total volume was similarly decreased; trabecular thickness was unchanged
      while increased trabecular spacing was observed. Dynamic histomorphometry
      demonstrated a 25% decrease in mineral apposition. Biochemically, control and PKU
      animals have similar plasma cortisol, adrenocorticotropic hormone, and 25
      hydroxyvitamin D. PKU animals show moderately increased plasma parathyroid
      hormone while plasma calcium and phosphate are reduced. These data are consistent
      with a mineralization defect. The effect of hyperphenylalaninemia on bone
      maturation was assessed in vitro employing bone-derived mesenchymal stem cells
      (MSCs) and their differentiation into bone. Using standard culture conditions,
      PAH deficient MSCs differentiate into bone as assessed by in situ alkaline
      phosphatase activity and mineral staining. However, PAH deficient MSCs cultured
      in 1200 MUM PHE (metric defining classical PKU) show significantly reduced
      mineralization. These data are the first biological evidence demonstrating a
      negative impact of hyperphenylalaninemia upon bone maturation. In PAH deficient
      MSCs, expression of Col1A1 and Rankl are suppressed by hyperphenylalaninemia
      consistent with reduced bone formation and bone turnover. Osteopenia is intrinsic
      to PKU pathology in untreated Pahenu2 animals and our data suggests PHE toxicity
      participates by inhibiting mineralization in the course of MSC bone
      differentiation.

PMID- 30201327
TI  - Molecular characterization, by digital PCR analysis of four HMBS gene mutations
      affecting the ubiquitous isoform of Porphobilinogen Deaminase (PBGD) in patients
      with Acute Intermittent Porphyria (AIP).
AB  - Genetic variants in promoters and alternative-splicing lesions require to be
      experimentally tested in order to validate them as causatives of a disease. The
      digital PCR (dPCR) approach, which is an alternative to the classical qPCR, is an
      innovative and a more sensitive method for the detection and quantification of
      nucleic acids. In the present study, we identified four HMBS gene mutations
      affecting the ubiquitous isoform of porphobilinogen deaminase (PBGD) and
      established a dPCR protocol which would be able to detect the different
      transcripts of this gene. With the application of this method, we were able to
      characterize the functional roles of these four genetic variants, demonstrating
      that all these mutations were causatives of the non-erythroid variant of the
      acute intermittent porphyria (AIP) disease.

PMID- 30201329
TI  - Rate and predictors of prescription of lumacaftor - Ivacaftor in the 18 months
      following approval in the United States.
AB  - RATIONALE: Lumacaftor-ivacaftor (LUM-IVA) was approved in the US in 2015 for
      patients with CF aged >12 homozygous for the delF508 mutation, and patients aged
      6 to 12 in 2016. OBJECTIVES: To examine the rate of initial LUM-IVA prescriptions
      following approval. METHODS: We compared patients eligible for LUM-IVA in the CF
      Foundation Patient Registry with and without prescriptions in 2015-2016. RESULTS:
      5534 (53%) eligible patients had reported prescriptions. Prescription rate in
      children ages 6-11 was 19% and 61% among patients >=12 years old. Individuals
      >=12 with prescriptions more likely observed among those with private insurance,
      clinical trial participation, ages 18-30, FEV1 < 90%, more pulmonary
      exacerbations, and more use of chronic medications. CONCLUSIONS: LUM-IVA uptake
      was less rapid than what was previously observed for ivacaftor, a CFTR modulator
      approved for a different population. Age, insurance status, disease severity and
      use of other therapies differed in those prescribed LUM-IVA in the initial post
      approval period.

PMID- 30201330
TI  - Bile acid homeostasis in gastrointestinal and metabolic complications of cystic
      fibrosis.
AB  - With the improved treatment of the pulmonary complications of cystic fibrosis
      (CF), gastrointestinal problems have become more important in the morbidity in
      CF. A hallmark of the gastrointestinal phenotype of CF, apart from pancreatic
      insufficiency, is a disruption of bile acid homeostasis. Bile acid homeostasis is
      important for many gastrointestinal processes including fat absorption,
      inflammation, microbial composition, as well as regulation of whole body energy
      metabolism. This review describes the impairment of bile acid homeostasis in CF,
      its possible consequences for gastrointestinal and metabolic complications and
      its potential as a target for therapy.

PMID- 30201328
TI  - Male-specific epistasis between WWC1 and TLN2 genes is associated with
      Alzheimer's disease.
AB  - Systematic epistasis analyses in multifactorial disorders are an important step
      to better characterize complex genetic risk structures. We conducted a hypothesis
      free sex-stratified genome-wide screening for epistasis contributing to
      Alzheimer's disease (AD) susceptibility. We identified a statistical epistasis
      signal between the single nucleotide polymorphisms rs3733980 and rs7175766 that
      was associated with AD in males (genome-wide significant pBonferroni
      corrected=0.0165). This signal pointed toward the genes WW and C2 domain
      containing 1, aka KIBRA; 5q34 and TLN2 (talin 2; 15q22.2). Gene-based meta
      analysis in 3 independent consortium data sets confirmed the identified
      interaction: the most significant (pmeta-Bonferroni-corrected=9.02*10-3) was for
      the single nucleotide polymorphism pair rs1477307 and rs4077746. In functional
      studies, WW and C2 domain containing 1, aka KIBRA and TLN2 coexpressed in the
      temporal cortex brain tissue of AD subjects (beta=0.17, 95% CI 0.04 to 0.30,
      p=0.01); modulated Tau toxicity in Drosophila eye experiments; colocalized in
      brain tissue cells, N2a neuroblastoma, and HeLa cell lines; and
      coimmunoprecipitated both in brain tissue and HEK293 cells. Our finding points
      toward new AD-related pathways and provides clues toward novel medical targets
      for the cure of AD.

PMID- 30201331
TI  - Effects of high-intensity ultrasound process parameters on the phenolic compounds
      recovery from araticum peel.
AB  - In this work, we investigated the effects of the nominal ultrasonic power (160
      640 W) and process time (0.5-5.0 min) on the phenolic compounds recovery and
      antioxidant activity from araticum peel. The individual and synergistic effects
      of the process variables on the phenolic recovery were estimated using a full
      factorial experimental design. Operating at high nominal ultrasonic powers was
      possible to obtain high phenolic yields and antioxidant activities at short
      process times (<=5 min). The HPLC-ESI-QTOF-MS/MS analysis revealed that the
      araticum peel sample possessed 142 phytochemicals, 123 of which had not been
      reported in the literature for this raw material yet. The most abundant phenolic
      compounds recovered were epicatechin, rutin, chlorogenic acid, catechin and
      ferulic acid. Thus, high-intensity ultrasound technology proved to be a simple,
      efficient, fast and low environmental impact method for obtaining phenolic
      compounds from araticum peel. In addition, araticum peel showed to be a promising
      source bioactive natural phenolics for further applications in the food,
      nutraceutical, cosmetic and pharmaceutical industries.

PMID- 30201332
TI  - A multidimensional impedance platform for the real-time analysis of single and
      combination drug pharmacology in patient-derived viable melanoma models.
AB  - In today's development of anticancer drugs, there is an enormous demand for
      sensitive, non-invasive real-time screening technologies to identify
      pharmacodynamics/-kinetics of single and combined drugs with high precision. The
      combination of sophisticated drug sensitivity testing with advanced in vitro
      tumor models reflecting heterogeneous tumor behavior in vivo is needed to more
      reasonably predict therapeutic outcome in vivo. In this study, the benefits of
      our real-time, non-invasive multidimensional impedance platform over standard in
      vitro drug sensitivity assays were demonstrated quantitatively using an advanced
      melanoma model. Detailed pharmacological profiles of clinically established
      targeted therapeutics in single and combination treatment have been identified in
      patient tissue and isolated 2D/3D cell line cultures. Impedance spectroscopy
      revealed significant differences in tissue structure responsible for BRAF
      inhibitor pharmacokinetics in BRAFV600E tumor microfragments and cell lines.
      Remarkably, BRAF-/MEK inhibitor combination treatment of direct patient-derived
      tissue, but not melanoma cell lines, resulted in short-term antagonistic effects
      consistent with in vivo findings. In contrast, the clinically validated
      resistance delay and thus long-term synergy of targeted therapeutics in advanced
      melanoma models has been demonstrated using impedance technology. The results
      demonstrate limited clinical transferability of 2D/3D cancer cell line-based
      chemosensitivity data and underline the importance of in vivo-like direct patient
      derived tissue for predictive drug studies. Our non-invasive and highly sensitive
      multidimensional impedance platform offers great potential for quantifying short-
      and long-term drug kinetics and synergies to identify the most effective drug
      combinations in advanced cancer models, thereby improving personalized drug
      development and treatment planning and ultimately, overall patient outcomes.

PMID- 30201333
TI  - Progress in the development of olfactory-based bioelectronic chemosensors.
AB  - Artificial chemosensory devices have a wide range of applications in industry,
      security, and medicine. The development of these devices has been inspired by the
      speed, sensitivity, and selectivity by which the olfactory system in animals can
      probe the chemical nature of the environment. In this review, we examine how
      molecular and cellular components of natural olfactory systems have been
      incorporated into artificial chemosensors, or bioelectronic sensors. We focus on
      the biological material that has been combined with signal transduction systems
      to develop artificial chemosensory devices. The strengths and limitations of
      different biological chemosensory material at the heart of these devices, as well
      as the reported overall effectiveness of the different bioelectronic sensor
      designs, is examined. This review also discusses future directions and challenges
      for continuing to advance development of bioelectronic sensors.

PMID- 30201334
TI  - Highly sensitive olfactory biosensors for the detection of volatile organic
      compounds by surface plasmon resonance imaging.
AB  - Nowadays, monitoring of volatile organic compounds (VOCs) is very important in
      various domains. In this work, we aimed to develop sensitive olfactory biosensors
      using odorant binding proteins (OBPs) as sensing materials. Three rat OBP3
      derivatives with customized binding properties were designed and immobilized on
      the same chip for the detection of VOCs in solution by surface plasmon resonance
      imaging (SPRi). We demonstrated that the proteins kept their binding properties
      after the immobilization under optimized conditions. The obtained olfactory
      biosensors exhibited very low limits of detection in both concentration (200 pM
      of beta-ionone) and in molecular weight of VOCs (100 g/mol for hexanal). Such a
      performance obtained with SPRi in solution is especially remarkable. We
      hypothesized that the binding of VOCs to the active sites of OBPs induced a local
      conformational change in the proteins. This change would  give rise to a
      variation of refractive index, to which SPRi is extremely sensitive. In addition,
      the olfactory biosensors showed a high selectivity especially at relatively low
      VOC concentrations. With optimized regeneration procedures, they also showed very
      good repeatability not only from measurement to measurement but also from chip to
      chip with a lifespan up to almost two months. These olfactory biosensors are
      particularly interesting for trace detection of VOCs in solution.

PMID- 30201335
TI  - Therapeutic applications of zebrafish (Danio rerio) miRNAs linked with human
      diseases: A prospective review.
AB  - MicroRNAs (miRNAs) are the class of small, non-coding RNAs that are produced from
      precursor transcripts by subsequent processing steps mediated by members of the
      RNaseIII family, Dicer and Drosha protein within cell. The importance of
      zebrafish miRNAs in regulation of normal cellular development and support to
      various kinds of metabolism process. Although the zebrafish model provides a
      fundamental platform for the study of developmental biology but recent work with
      zebrafish model has expanded its appliance to a broad range of experimental
      studies relevant to different kind of human diseases. Presently, the zebrafish
      model is used for the study of cardiovascular disease, schizophrenia, bipolar I
      disorder in eyes, psoriasis, spinal cord injury, cancer and diabetes that showing
      in some selected miRNAs are regulate these diseases in molecular levels. Here, a
      superior drive performed to depict the fundamental utilization of the zebrafish
      miRNAs that targeted to several clinical diseases connected to human. This review
      aims to provide a summary of understanding of the cellular mechanism which is
      responsible for selected diseases and suggests some therapeutic application for
      inhibition of miRNA functions.

PMID- 30201336
TI  - Identification of a novel mutation of the NTRK1 gene in patients with congenital
      insensitivity to pain with anhidrosis (CIPA).
AB  - INTRODUCTION: Congenital insensitivity to pain with anhidrosis (CIPA) is a rare
      autosomal recessive disorder resulting from NTRK1 mutation. Over 105 NTRK1
      mutations have been reported in CIPA patients worldwide. The causative NTRK1
      mutations lead to loss of function of the TrkA protein, an important ligand for
      nerve growth factor (NGF), and therefore induce various clinical phenotypes
      associated with neuron maturation defects. MATERIALS AND METHODS: Three patients
      from unrelated families with CIPA were subjected to detailed clinical
      examinations. Blood samples were collected from all the patients and their
      available family members, as well as 200 healthy volunteers. Sanger sequencing
      for all the exons and splicing sites of NTRK1 was performed on all samples. The
      phenotype-genotype relationship and genetic epidemiology of Chinese CIPA patients
      were also analysed. RESULTS: A total of four different NTRK1 mutations [c.851
      33T>A, c.44G>A (p.Trp15*), c.287+2dupT, c.1549G>C (p.Gly517Arg)] were identified
      in these families, and c.1549G>C (p.Gly517Arg) was a novel mutation that had not
      been reported previously. The 'mild' manifestations observed in patients with
      c.851-33T>A indicated this mutation as a 'mild' mutation. After reviewing studies
      reporting mutations in Chinese CIPA patients, we speculate the mutation c.851
      33T>A is one of the founder mutations in the Chinese population. CONCLUSIONS: Our
      research expanded the spectrum of the NTRK1 mutations associated with CIPA
      patients, provided additional clues relating to the phenotype-genotype
      relationship in CIPA, and summarized the features of the genetic epidemiology of
      CIPA in the Chinese ethnic group.

PMID- 30201337
TI  - Hyperoside and let-7a-5p synergistically inhibits lung cancer cell proliferation
      via inducing G1/S phase arrest.
AB  - Lung cancer remains one of the most aggressive human malignancies with a low
      survival rate. Hyperoside (quercetin-3-O-beta-d-galactopyranoside) is a flavonol
      glycoside with an anti-cancer activity. The microRNA-let-7 was widely regarded as
      a tumor suppressor in human tumors. Here, we investigated the role of hyperoside
      and let-7a-5p on the lung cancer cell proliferation, cell cycle and apoptosis in
      A549 cells in vitro. Our results showed that hyperoside could inhibit the
      proliferation of A549 cells through inducing apoptosis and G1/S phase arrest. Let
      7a-5p could inhibit the proliferation of A549 cells via inhibiting the process of
      G1/S phase. Additionally, hyperoside and let-7a-5p had a synergetic effect on
      suppressing the proliferation of A549 cells; microRNA-let-7a-5p directly
      regulated the expression of CCND1 in A549 cells. Our study illustrated that
      hyperoside and microRNA-let7a-5p might provide a synergistic effect on anti
      cancer, which may provide a new idea for lung cancer treatment.

PMID- 30201338
TI  - The miR-143/145 cluster reverses the regulation effect of KLF5 in smooth muscle
      cells with proliferation and contractility in intracranial aneurysm.
AB  - Alterations in vascular smooth muscle cells (VSMCs) contribute to the
      pathogenesis of intracranial aneurysms (IAs), but the molecular mechanisms of
      these alterations are unclear. The aim of this study was therefore to identify
      the molecular mechanism of VSMC-mediated IAs at clinical and cellular levels. We
      used bioinformatic and biochemical analyses to show that the microRNA (miR)
      143/145 cluster was involved in various biological processes related to aneurysm
      formation. Clinical studies showed that the miR-143/145 cluster was downregulated
      in IA patients when compared with healthy subjects. However, KLF5 expression was
      upregulated in IA patients. In vitro experiments showed that overexpression of
      the miR-143/145 cluster inhibited proliferation and migration of VSMCs, but
      increased contractile protein expression and decreased matrix metalloproteinase-2
      and -3. KLF5 overexpression had the opposite effect, even reversing the
      protective effect of the miR-143/145 cluster on IAs. Bifluorescein report
      experiments further confirmed that both miR-143 and miR-145 interacted with the
      3'-UTR of KLF5 and inhibited post-transcriptional expression of KLF5. Taken
      together, the results showed that VSMC phenotypic modulation with upregulation of
      KLF5 by downregulation of the miR-143/145 cluster played an important role in
      formation and growth of IAs. The process of IA formation was reversed by
      overexpression of the miR-143/145 cluster. Together, the results provided a
      theoretical basis for further investigation of the potential clinical prevention
      and treatment of IAs.

PMID- 30201339
TI  - Porcine ISG15 modulates the antiviral response during pseudorabies virus
      replication.
AB  - Pseudorabies virus (PRV) is one of the most vital pathogens of swine, leading to
      huge economic losses to the pig industry. Functioning in innate immunity, type-I
      interferon (IFN) plays a vital role in initial stage of viral infection. ISG15,
      an IFN-stimulated ubiquitin-like protein, is highly increased during virus
      infection and participates in the IFN-mediated antiviral immune response.
      However, limited attention has been paid to the functional role of porcine ISG15
      (pISG15) in PRV infection. In this study, we generated a PK15 inducible cell line
      stably expressing the pISG15 gene and investigated the potential anti-PRV
      response of pISG15. We demonstrated that pISG15 was upregulated in an early stage
      of PRV infection, and pISG15 overexpression efficiently inhibited PRV replication
      by reducing the viral titers and mRNA levels of PRV, and also increased
      expression of IFN-beta and activation of the ISRE promoter. However, knockdown of
      pISG15 by siRNA did not affect PRV replication, and potentiated IFN-I-mediated
      signaling, resulting in an increase in antiviral response in the process of PRV
      infection. The results showed that pISG15 has a potential immunodulatory role in
      cellular antiviral response against PRV.

PMID- 30201340
TI  - Moraxella Keratitis: Analysis of risk factors, clinical characteristics,
      management and treatment outcomes.
AB  - PURPOSE: To analyze the risk factors, clinical characteristics, management, and
      treatment outcomes of culture-proven cases of Moraxella keratitis at our center.
      DESIGN: Retrospective observational case series METHODS: 39 culture-proven cases
      of Moraxella keratitis (39 eyes) diagnosed and treated between January 2003 and
      April 2018 at the University of Pittsburgh Medical Center were identified and
      retrospectively reviewed for ocular and systemic risk factors, treatment
      modalities, outcomes, as well as antimicrobial sensitivity and resistance data.
      RESULTS: The mean age of 39 patients was 63.0 (range 4-95 years) with median
      follow-up time of 170 days. 34/39 patients (87.2%) had an ocular risk factor, the
      most common of which were blepharitis in 12 (30.8%), dry eyes in 12 (30.8%), and
      history of ocular surgery in 9 (23.1%). History of diabetes mellitus was found in
      8 patients (20.5%). 36 of 39 patients (92.3%) received a fluoroquinolone (92.3%)
      and 30 of 39 (76.7%) received topical fortified antibiotics. Resistance to
      fluoroquinolones, gentamicin, and tobramycin was seen in one case each
      respectively. 4 patients (10.3%) required tarsorrhaphy, 6 patients (15.4%)
      required penetrating keratoplasty, and 1 patient required enucleation. Of the 35
      patients for who visual acuity information was available, 19 (54.3%) were count
      fingers or worse at most recent follow-up. CONCLUSIONS: Ocular risk factors,
      especially poor ocular surface, were identified in the vast majority of patients
      with Moraxella keratitis. Moraxella isolates in our study were susceptible to
      fluoroquinolones and aminoglycosides. Many patients required surgical
      intervention and the final visual acuity was often poor.

PMID- 30201341
TI  - Enhanced Ectasia Detection Using Corneal Tomography And Biomechanics.
AB  - PURPOSE: To test the accuracy of the Tomographic and Biomechanical Index (TBI)
      for ectasia detection in an independent population from the original study.
      DESIGN: Retrospective observational case-control study. SUBJECTS: Patients were
      grouped according to clinical diagnosis including corneal topography (front
      surface curvature). METHODS: Normal group (N group) included 1 eye randomly
      selected from 312 patients with normal corneas; keratoconus group (KC group)
      included 1 eye randomly selected from 118 patients with keratoconus; a non
      operated ectatic eye from sixty-seven patients with very asymmetric ectasia (57
      eyes, VAE-E group), and the non-operated fellow eye with normal topography (57
      eyes, VAE-NT group). MAIN OUTCOME MEASURES: The ability of TBI to distinguish
      normal and ectatic corneas; and comparison with other indexes, including the
      Belin/Ambrosio Deviation Index (BAD-DI), and the Corvis Biomechanical Index
      (CBI), considering the areas under receiver operating characteristic curves
      (AUCs). RESULTS: The AUC of the TBI was statistically higher than all other
      tested parameters (DeLong, p<.001). Considering all cases, the cut-off value of
      0.335 for the TBI provided a sensitivity of 94.4% and a specificity of 94.9%
      (AUC=0.988; 95% Confidence interval [CI] 0.982 to 0.995). Considering the VAE-NT
      group, optimized TBI cut-off value of 0.295 provided a sensitivity of 89.5% and a
      specificity of 91.0% (AUC=0.960; 95% CI 0.937 to 0.983). CONCLUSION: The TBI was
      more accurate than all parameters tested for differentiating normal from ectatic
      corneas. The TBI may epitomize ectasia susceptibility, and distinguish cases with
      fruste disease from true unilateral cases among the eyes with normal topography
      VAE patients.

PMID- 30201342
TI  - Gastrointestinal Stromal Tumor, or Another Tumor Type?

PMID- 30201344
TI  - Dysphagia in a Patient With End-Stage Renal Disease.

PMID- 30201343
TI  - Personalized Treatment in Inflammatory Bowel Disease: For Another Time.

PMID- 30201345
TI  - Multiple polypoid lesions in the ileum after treatment for primary ileal
      follicular lymphoma.

PMID- 30201346
TI  - An Unusual Cause of Perianal Ulceration in an HIV-Negative Patient.

PMID- 30201347
TI  - Diffuse Abdominal Pain With a Rare Cause.

PMID- 30201348
TI  - An Unusual Cause of Acute Severe Hepatitis.

PMID- 30201349
TI  - Atypical Colonic Polyp.

PMID- 30201350
TI  - A Rare Case of Colonic Intussusception in an Adult.

PMID- 30201351
TI  - Appendiceal Mass With a Palpable Nodule on the Thigh.

PMID- 30201353
TI  - Is It a Refractory Celiac Disease?

PMID- 30201354
TI  - A Rare Cause of Hepatitis.

PMID- 30201355
TI  - Urinary Tract Infection and Vaginal Purulent Flow in a Patient With Recurrent
      Sigmoiditis.

PMID- 30201356
TI  - A Rare Cause of Acute Pancreatitis.

PMID- 30201357
TI  - An Unusual Cause of Esophageal Obstruction and Hematemesis.

PMID- 30201358
TI  - Methotrexate Monotherapy for Induction and Maintenance of Clinical Remission in
      Ulcerative Colitis: Dead on Arrival.

PMID- 30201359
TI  - Does Ribavirin Still Have a Role in Sofosbuvir and Velpatasvir Therapy for
      Patients With HCV Genotype 3 Infection and Cirrhosis?

PMID- 30201360
TI  - Misoprostol for Aspirin-Induced Small Bowel Enteropathy: A Small Step in the
      Right Direction.

PMID- 30201361
TI  - Manipulating the Gut Microbiome as a Treatment Strategy for Functional
      Gastrointestinal Disorders.

PMID- 30201363
TI  - Should We Abandon Current Hepatocellular Carcinoma Screening Practices?

PMID- 30201362
TI  - Healthy Lifestyle Factors Associated With Lower Risk of Colorectal Cancer
      Irrespective of Genetic Risk.
AB  - BACKGROUND & AIMS: The combined effects of healthy lifestyle factors on
      colorectal cancer (CRC) risk are unclear. We aimed to develop a healthy lifestyle
      score, to investigate the joint effects of modifiable lifestyle factors on
      reduction of CRC risk and determine whether associations differ with genetic
      risk. METHODS: We collected data from a large population-based case-control study
      in Germany and used multiple logistic regression analyses to examine associations
      between the healthy lifestyle score (derived from 5 modifiable lifestyle factors:
      smoking, alcohol consumption, diet, physical activity, and body fatness) and CRC
      risk. We created a genetic risk score, based on 53 risk variants, to investigate
      the association of the healthy lifestyle score and risk of CRC, stratified by
      genetic risk. RESULTS: We included 4092 patients with CRC and 3032 individuals
      without CRC (controls) in our analysis. In adjusted models, compared with
      participants with 0 or 1 healthy lifestyle factor, participants with 2 (odds
      ratio [OR] 0.85; 95% confidence interval [CI] 0.67-1.06), 3 (OR 0.62; 95% CI 0.50
      0.77), 4 (OR 0.53; 95% CI 0.42-0.66), or 5 (OR 0.33; 95% CI 0.26-0.43) healthy
      lifestyle factors had increasingly lower risks of CRC (P trend <.0001). We found
      no differences among subgroups stratified by genetic risk score, history of
      colonoscopy, or family history of CRC. Overall, 45% of CRC cases (95% CI 34%-53%)
      could be attributed to nonadherence to all 5 healthy lifestyle behaviors.
      CONCLUSIONS: In a large population-based case-control study, we identified a
      combination of lifestyle factors that appears to reduce risk of CRC, regardless
      of the patient's genetic profile. These results reinforce the importance of
      primary prevention of CRC.

PMID- 30201364
TI  - ROCKin' Intestinal Cell Fate: A Potential Avenue to Improve Glucose Sensitivity.

PMID- 30201365
TI  - Cytokinesis and the Hippo Pathway: New Molecular Links Between Intimate Partners.

PMID- 30201366
TI  - Unusual Pick Up by Capsule Endoscopy.

PMID- 30201367
TI  - Comparison of accuracy of presepsin and procalcitonin concentrations in
      diagnosing sepsis in patients with and without acute kidney injury.
AB  - BACKGROUND: Levels of the biomarkers presepsin and procalcitonin are affected by
      renal function. We evaluated the accuracies of presepsin and procalcitonin levels
      for diagnosing sepsis in patients with and without acute kidney injury (AKI).
      METHODS: We evaluated patients with presepsin and procalcitonin data, and
      classified them into AKI and non-AKI groups based on the Kidney Disease Improving
      Global Outcomes criteria. Each group was then subdivided according to sepsis
      status for each stage of AKI. Receiver operating characteristic curve analyses
      were used to investigate the accuracies of biomarker levels for diagnosing
      sepsis. RESULTS: In the non-AKI group, the area under the curves (AUCs) for
      procalcitonin and presepsin levels were 0.897 and 0.880, respectively (p = .525)
      and optimal cut-off values were 0.10 ng/ml (sensitivity: 85.1%, specificity:
      79.1%) and 240 pg/ml (sensitivity: 80.9%, specificity: 83.2%), respectively. In
      the stage 3 subgroup, the AUC for procalcitonin (0.946) was significantly higher
      than that for presepsin (0.768, p < .001). The optimal cut-off values for
      diagnosing sepsis were 4.07 ng/ml (sensitivity: 87.2%, specificity: 93.5%) for
      procalcitonin and 500 pg/ml (sensitivity: 89.7%, specificity: 59.7%) for
      presepsin. CONCLUSIONS: In patients with severe AKI, the accuracy of the
      diagnosis of sepsis with procalcitonin was significantly higher than with
      presepsin.

PMID- 30201368
TI  - Neutrophil-lymphocyte ratio is associated with all-cause mortality among
      critically ill patients with acute kidney injury.
AB  - BACKGROUND: Inflammation plays a critical role in the development of acute kidney
      injury (AKI). Neutrophil-lymphocyte ratio (NLR) is a biomarker of systemic
      inflammation used to predict the prognostic outcome of several diseases. We
      conducted a retrospective cohort study to investigate if NLR can be used as a
      biomarker to predict the mortality of AKI. METHODS AND RESULTS: Records of
      critically ill patients with AKI were extracted from the Medical Information Mart
      for Intensive Care Database III version 1.3 (MIMIC-III v1.3). The primary outcome
      was 30-day mortality and the two secondary outcomes were in hospital and 90-day
      mortality. We used the Cox proportional hazards models to assess the association
      between different categories of NLR and outcomes. This analysis included data for
      13,678 eligible subjects, with a total of 2,588 30-day, 2,224 in-hospital and
      3,545 90-day deaths during the follow-up period. For 30-day mortality, an
      increased risk of mortality was associated with a higher level of NLR. The HR
      (95% confidence interval [CI]) of upper tertile (NLR > 12.14) was 1.37 (1.17
      1.60) in a multivariate model when compared with that of the lower tertile (NLR <
      5.55). In the quintile analysis, we confirmed the upward trend with HR (95% CI)
      of the fifth quintile (NLR > 17.4) of 1.35 (1.08, 1.69) in a multivariate model
      compared to the first quintile (NLR < 3.82). A similar tendency was observed for
      90-day mortality. In the analysis of in-hospital mortality, the HR of fifth
      quintile (NLR > 17.4) showed a slight decrease. CONCLUSIONS: Our analysis
      indicates that a higher level of NLR is associated with increased risk of 30-day
      and 90-day mortality in AKI patients. The similar upward trend is not detected in
      analysis of in-hospital mortality.

PMID- 30201369
TI  - Dyslipidemias in clinical practice.
AB  - Most dyslipidemic conditions have been linked to an increased risk of
      cardiovascular disease. Over the past few years major advances have been made
      regarding the genetic and metabolic basis of dyslipidemias. Detailed
      characterization of the genetic basis of familial lipid disorders and knowledge
      concerning the effects of environmental factors on the expression of
      dyslipidemias have increased substantially, contributing to a better diagnosis in
      individual patients. In addition to these developments, therapeutic options to
      lower cholesterol levels in clinical practice have expanded even further in
      patients with familial hypercholesterolemia and in subjects with cardiovascular
      disease. Finally, promising upcoming therapeutic lipid lowering strategies will
      be reviewed. All these advances will be discussed in relation to current clinical
      practice with special focus on common lipid disorders including familial
      dyslipidemias.

PMID- 30201370
TI  - Prevalence and influencing factors of the high nil-control spot count in T
      SPOT.TB: A matched case-control study.
AB  - BACKGROUND: T-SPOT.TB may yield indeterminate results, including high nil
      responses and insufficient mitogen responses. We explored the incidence and risk
      factors of high nil responses. METHODS: A 1:1 matched case-control study of
      patients who underwent T-SPOT.TB tests in Peking Union Medical College Hospital
      from Jan 1, 2015 to Apr 30, 2017 was conducted. High nil responses were defined
      as >10 spots in negative control wells. Cases and controls were matched based on
      when the tests were performed. Demographic, clinical and laboratory data were
      obtained from the Medical Record System. RESULTS: A total of 644 out of 36,316
      (1.76%, 95% CI: 1.63%-1.90%) patients presented with high nil responses (280
      cases and 280 controls were enrolled). Multivariate analysis revealed that male
      (OR = 1.882, 95% CI: 1.222-2.899), Behcet's disease (OR = 7.764, 95% CI: 1.714
      35.167), heavy use of corticosteroids within a month (OR = 0.357, 95% CI: 0.138
      0.921, for >1000 mg group) and hypoalbuminemia (OR = 0.385, 95% CI: 0.241-0.615)
      are significantly associated with high nil responses. CONCLUSIONS: High nil
      responses in T-SPOT.TB assays are quite rare. Male gender and Behcet's disease
      are suggested as independent risk factors, while recent excessive use of
      corticosteroids and hypoalbuminemia seem to be independent protective factors.

PMID- 30201371
TI  - Diagnostic validation and interpretation of longitudinal circulating biomarkers
      using a biomarker response characteristic plot.
AB  - BACKGROUND: Serum-based tumor biomarkers are used to monitor cancer treatment,
      while clear guidance on the clinical usage is often lacking. We describe a
      graphical presentation to support diagnostic accuracy studies and clinical
      interpretation of longitudinal biomarker data. METHODS: A biomarker response
      characteristic (BReC) plot was designed. To allow demonstration of the BReC plot
      application, software was developed that supported 1) dynamic generation of BReC
      plots, and 2) diagnostic accuracy studies of biomarker response-based medical
      tests. The BReC plot application was demonstrated using serial carcinoembryonic
      antigen (CEA) and Cyfra 21.1 results from 216 patients with metastasized non
      small cell lung cancer, treated with Nivolumab in routine clinical practice.
      RESULTS: The developed software supported the generation of BReC plots and
      diagnostic validation of biomarker response-based medical tests by generating the
      sensitivity, specificity and predictive values. Obtained BReC plots showed a
      clear relationship between clinical outcome and CEA and Cyfra 21.1 responses.
      Furthermore, using BReC plots, CEA and Cyfra 21.1 based medical tests were
      designed with a sensitivity for detection of treatment failure of 0.34 and 0.35
      and a specificity of 0.96. CONCLUSIONS: The BReC plot appears to support
      diagnostic validation studies and the interpretation of longitudinal biomarkers
      though further validation is warranted.

PMID- 30201372
TI  - Urinary kidney injury molecule-1 in renal disease.
AB  - Kidney injury molecule-1 (KIM-1), a type l transmembrane glycoprotein, is
      recognized as a potential biomarker for detection of tubular injury in the main
      renal diseases. Urinary KIM-1 increases rapidly upon the tubular injury, and its
      levels are associated with the degree of tubular injury, interstitial fibrosis,
      and inflammation in the injured kidney. Currently, the investigation of kidney
      diseases is usually performed through the assessment of serum creatinine and
      urinary albumin. However, these biomarkers are limited for the early detection of
      changes in renal function. Besides, the tubular injury appears to precede
      glomerular damage in the pathophysiology of renal diseases. For these reasons,
      the search for sensitive, specific and non-invasive biomarkers is of interest.
      Therefore, the purpose of this article is to review the physiological mechanisms
      of KIM-1, as well to present clinical evidence about the association between
      elevated urinary KIM-1 levels and the main renal diseases such as chronic kidney
      disease, diabetic kidney disease, acute kidney injury, and IgA nephropathy.

PMID- 30201373
TI  - Metabolic disorders and inflammation are associated with familial combined
      hyperlipemia.
AB  - BACKGROUND: Familial Combined Hyperlipidemia (FCH) is related to different
      metabolic disorders. The objective of this study was to evaluate the presence of
      alterations of hydrocarbonated metabolism and lipid profile together with
      inflammatory and adhesion molecules in subjects with FCH compared to controls.
      METHODS: 75 HFC patients and 75 healthy individuals were studied. Glucose,
      insulin, HOMA-IR index and lipid parameters, in addition to anti-oxidized LDL
      antibodies (Anti ox-LDL), small and dense LDL (sdLDL) and HDL subfractions,
      proinflammatory cytokines and adhesion molecules were measured. RESULTS: FCH
      patients showed higher levels of hydrocarbonated metabolism parameters, total
      cholesterol, triglycerides, LDLc, Apolipoprotein B and non-HDLc (p < .001), and
      lower levels of HDLc (p < .001) and Apolipoprotein AI (p < .05) than controls. In
      addition, the inflammatory markers hsCRP, IL-6, IL-8, P-selectin, E-selectin and
      ICAM were all higher with (p < .05) respect to controls. The increase of sdLDL
      was correlated with the presence of IR and IL-6 levels. Significant differences
      in diameter and percentage of phenotype B LDL, small HDL subfractions and Anti ox
      LDL were also detected between patients and controls. CONCLUSIONS: The lipid
      characteristics of FCH are confirmed by IR and a low grade inflammatory state in
      patients, and are associated with the predominance of sdLDL and Anti ox-LDL.

PMID- 30201375
TI  - Inhibition of alpha2C-adrenoceptors ameliorates cisplatin-induced acute renal
      failure in rats.
AB  - Nephrotoxicity is a major adverse reaction of the anticancer drug, cisplatin. We
      investigated the renoprotective effects of the alpha2-adrenoceptor antagonist,
      yohimbine and selective alpha2C-adrenoceptor antagonist, JP-1302, in cisplatin
      treated Sprague Dawley rats. Rats were given a single intravenous dose of 7.5
      mg/kg cisplatin and then yohimbine or JP-1302 was administered intraperitoneally
      at 0.1 or 3 mg/kg/day, respectively, for four days. Renal functional parameters,
      such as blood urea nitrogen, plasma creatinine, creatinine clearance and renal
      venous norepinephrine concentrations were measured. Kidney tissue damage and
      tumour necrosis factor-alpha (TNF-alpha) and monocyte chemoattractant protein-1
      (MCP-1) mRNA levels were assessed after the animals were euthanized. Cisplatin
      treatment aggravated the kidney functional parameters of blood urea nitrogen,
      plasma creatinine and creatinine clearance. Renal venous norepinephrine
      concentrations were also elevated after cisplatin administration. Treatment with
      yohimbine or JP-1302 clearly ameliorated kidney function and cell apoptosis.
      These treatments suppressed elevated renal plasma norepinephrine, TNF-alpha, MCP
      1 and cleaved caspase 3 expressions which occurred after administration of
      cisplatin. These results suggest that yohimbine can prevent cisplatin-induced
      renal toxicity associated with acute kidney injury by suppressing cytokine
      expression through alpha2C-adrenoceptors.

PMID- 30201374
TI  - [Smoking and alcohol cessation programs in patients with head and neck cancer].
AB  - Most head and neck cancers are associated with smoking and alcohol exposure.
      Smoking and alcohol cessation (ASC) is associated with improved quality of life,
      cancer therapy efficacy, decreased treatment-related and cardiovascular risks,
      and is expected to decrease the risk of second primary tumor. It is therefore a
      high priority in the plan of care. However, results of current ASC programs are
      disappointing and understanding the reasons of this is critical. We started a
      qualitative study in 6 academic centers including 3 university hospitals, one
      regional hospital and one comprehensive cancer center. We first interviewed
      surgeons and care givers involved in the management of head and neck cancers.
      Poor communication between stakeholders, absence of alignment of care goals
      between patients, surgeons and other caregivers, and low level of understanding
      by patients of the benefits of ASC were felt to represent frequent obstacles to
      successful outcome. More work is ongoing within the context of our IHNPACT
      umbrella protocol to identify hurdles associated with successful ASC.

PMID- 30201377
TI  - The long duration of action of the second generation antihistamine bilastine
      coincides with its long residence time at the histamine H1 receptor.
AB  - Drug-target binding kinetics has recently attracted considerable interest in view
      of the potential predictive power for in vivo drug efficacy. The recently
      introduced antihistamine bilastine has a long duration of in vivo drug action,
      which outlasts pharmacological active bilastine concentrations in blood. To
      provide a molecular basis for the long duration of action, we explored the
      kinetics of bilastine binding to the human histamine H1 receptor using
      [3H]mepyramine binding studies and compared its pharmacodynamics properties to
      the reference compounds fexofenadine and diphenhydramine, which have a long (60
      +/- 20 min) and short (0.41 +/- 0.1 min) residence time, respectively. Bilastine
      shows a long drug-target residence time at the H1 receptor (73 +/- 5 min) and
      this results in a prolonged H1 receptor antagonism in vitro (Ca2+ mobilization in
      Fluo-4 loaded HeLa cells), following a washout of unbound antagonist. Hence, the
      long residence time of bilastine can explain the observed long duration of drug
      action in vivo.

PMID- 30201376
TI  - Selective peroxisome proliferator-activated receptor-alpha modulator K-877
      regulates the expression of ATP-binding cassette transporter A1 in pancreatic
      beta cells.
AB  - ATP-binding cassette transporter A1 (ABCA1) protein is a pivotal regulator of
      cholesterol and phospholipid efflux from cells to high-density lipoprotein (HDL)
      particles. Pancreatic ABCA1 functions in beta cell cholesterol homeostasis and
      affects insulin secretion. We investigated the effect of pemafibrate (K-877), a
      novel selective PPARalpha modulator (SPPARMalpha), on pancreatic ABCA1
      expression. In vivo experiment, mice were divided into four treatment groups,
      namely, normal food plus placebo, high fat diet (HFD) plus placebo, normal food
      plus K-877 (0.3 mg/kg/day), or HFD plus K-877 (0.3 mg/kg/day), and treated for
      eight weeks. The results in vitro experiment indicate that K-877 treatment
      increased levels of ABCA1 mRNA, as well as protein, subsequently reduced the
      cellular cholesterol content in INS-1 cells. PPARalpha specific antagonist GW6471
      attenuate K-877 induced ABCA1 expression in INS-1 cells. ABCA1 promoter activity
      increased with K-877 treatment at concentration 1 MUM and 10 MUM. Glucose
      stimulated insulin secretion was ameliorated by K-877 treatment in INS-1 cells
      and isolated mouse islets. Although the expression of ABCA1 was reduced in mice
      with HFD treatment, both ABCA1 protein and mRNA levels were increased in mice
      with K-877 treatment. K-877 treatment improved glucose intolerance induced by HFD
      in mice. These findings raise the possibility that K-877 may affect insulin
      secretion by controlling ABCA1 expression in pancreatic beta cells.

PMID- 30201378
TI  - Penehyclidine hydrochloride preconditioning provides pulmonary and systemic
      protection in a rat model of lung ischaemia reperfusion injury.
AB  - Penehyclidine hydrochloride (PHC) is a new anticholinergic agent that provides
      protective effects in experimental models of heart and brain ischaemia as well as
      reperfusion (I/R) injury. In this study, we tested the hypothesis that PHC can
      alleviate lung ischaemia-reperfusion injury and improve pulmonary and systemic
      function in rats. PHC was administered intravenously at various doses (d= 0.1,
      0.3, 1, 3 mg/kg) to I/R rats. We used six indicators, including lung function,
      histologic examination, pulmonary oedema, oxidative stress, inflammatory
      responses, and apoptosis staining to quantify the pulmonary and systemic
      protective effects of PHC. Haematoxylin and eosin staining was used for pulmonary
      histologic examination. The expression of Toll-like receptor (TLR) 4, phospho
      inhibitor of NF-kappaB (p-IkappaB) and nuclear factor-kappa B (NF-kappaB) was
      analysed using western blotting. ELISA was conducted to detect inflammatory
      mediators. Oxidative stress markers as well as myeloperoxidase (MPO) were
      determined using an assay kit. PHC preconditioning (with concentrations ranging
      from 0.3 mg/kg to 3 mg/kg 30 min before the onset of I/R) significantly reduced
      lung histopathological changes, down regulated TLR4, p-IkappaB and NF-kappaB
      expression, and decreased inflammatory mediators as well as the total number of
      leukocytes and neutrophils in bronchoalveolar lavage (BAL) fluid and plasma. The
      lung tissue contents of reactive oxygen species (ROS), malondialdehyde (MDA), and
      MPO as well as pulmonary oedema formation decreased, while SOD (superoxide
      dismutase) activity was significantly upregulated. PHC preconditioning (with
      concentrations ranging from 1 mg/kg to 3 mg/kg) significantly improved the lung
      function and attenuated the apoptotic rate. The probable mechanism for this
      finding is the inhibition of proinflammatory mediators via the suppression of
      reactive oxygen species production and the TLR4/NF-kappaB signalling pathway.

PMID- 30201379
TI  - Irreversible proteasome inhibition with carfilzomib as first line therapy in
      patients with newly diagnosed multiple myeloma: Early in vivo cardiovascular
      effects.
AB  - Patients who experienced cardiovascular side effects during cancer therapy with
      carfilzomib for multiple myeloma had relapsed multiple myeloma, so have be
      previously treated with other cancer therapies. The present is a single center
      cohort study to evaluate early cardiovascular effects of administration of
      irreversible proteasome inhibitor carfilzomib in naive patients. We included 24
      patients and collected cardiovascular side effects, echocardiographic parameters
      and endothelial function at baseline and after 4 cycles. At early follow up we
      observed increase in blood arterial pressure values (mean change in systolic
      pressure of 10 mmHg (P-value < 0.01; diastolic arterial pressure and mean
      arterial pressure of 3.3 mmHg and 5.4 mmHg, both P-value < 0.01). Reactive
      hyperemia PAT index was reduced in the whole cohort by a mean of 0.46 points (P
      value < 0.01); diastolic function was changed: E-wave-deceleration-time (EDT) was
      reduced by 49,96 +/- 31 ms, P-value < 0.05 and early diastolic tissue Doppler
      velocity (e') by a mean value of 1.46 cm/s, P - value 0.04. At early follow up we
      did not observe events of grade 3 or 4. We observe correlation between events and
      endothelial dysfunction at baseline and age (OR 1.9, CI 95% 0.05-5.804, P- value:
      0.038 for RHI<1.67; OR 1,4, CI 95%0.99-2.56, P- value: 0.04 for age). Our results
      suggest that therapy with carfilzomib when used as first line therapy is
      responsible for increase in systemic blood pressure, alteration of endothelium
      mediated vascular dilatation and early myocardial diastolic dysfunction.

PMID- 30201380
TI  - Exercise ventilatory inefficiency in heart failure and chronic obstructive
      pulmonary disease.
AB  - BACKGROUND: Dyspnea on exertion is common to both heart failure (HF) and chronic
      obstructive pulmonary disease (COPD), and it is important to discriminate whether
      symptoms are caused by HF or COPD in clinical practice. The ventilatory
      equivalent for carbon dioxide (VE/VCO2) slope and VE intercept (a reflection of
      pulmonary dead space) are two candidate non-invasive indices that could be used
      for this purpose. Thus, we compared non-invasive indexes of ventilatory
      efficiency in patients with HF and preserved or reduced ejection fraction (HFpEF
      and HFrEF, respectively) or COPD. METHODS: Patients with HFpEF (n = 21), HFrEF (n
      = 20), and COPD (n = 22) patients performed cardiopulmonary exercise testing to
      volitional fatigue. VE and gas exchange were measured via breath-by-breath open
      circuit spirometry. All data from rest to peak exercise were used to calculate
      VE/VCO2 slope and VE intercept using linear regression. Receiver operating
      characteristic (ROC) curves were constructed to determine optimized cutoffs for
      VE/VCO2 slope and VE intercept to discriminate HFpEF and HFrEF from COPD.
      RESULTS: HFrEF patients had a greater VE/VCO2 slope than HFpEF and COPD patients
      (HFrEF: 40 +/- 9; HFpEF: 32 +/- 7; COPD: 32 +/- 7) (p < 0.01). COPD patients had
      a greater VE intercept than HFpEF and HFrEF patients (COPD: 3.32 +/- 1.66; HFpEF:
      0.77 +/- 1.23; HFrEF: 1.28 +/- 1.19 L/min) (p < 0.01). A VE intercept of 2.64
      L/min discriminated COPD from HF patients (AUC: 0.88, p < 0.01), while VE/VCO2
      slope did not (p = 0.11). CONCLUSION: These findings demonstrate that VE
      intercept, not VE/VCO2 slope, may discriminate COPD from both HFpEF and HFrEF
      patients.

PMID- 30201381
TI  - Mode of death and predictors of mortality in adult Fontan survivors: A Japanese
      multicenter observational study.
AB  - BACKGROUND: Mortality rates may be high in adult Fontan patients; however, the
      clinical determinants remain unclear. PURPOSE: We conducted a prospective
      multicenter study of adult Fontan survivors to determine the 5-year mortality
      rate and clarify the determinants. METHOD AND RESULTS: We followed 600 adult
      Fontan survivors from 40 Japanese institutions (307 men, 28 +/- 7 years old,
      follow-up: 18 +/- 6 years). The New York Heart Association (NYHA) functional
      class I and II was 51% and 42%, respectively. During the follow-up period of 4.1
      +/- 1.6 years, 33 patients died, and the 5-year survival rate was 93.5%. The mode
      of death was heart failure in 11 patients (34%), arrhythmia or sudden death in 8
      (24%), cancer in 5 (15%), perioperative problems and hemostatic problems in 4
      each (12% for each), and infection in 1 (3%). Left isomerism, prior
      hospitalization, protein losing enteropathy (PLE), pulmonary arteriovenous
      fistulae, NYHA functional class, impaired hemodynamics, hyponatremia, hepatorenal
      dysfunction, and use of diuretics were associated with a high mortality rate (p <
      0.05-0.0001). Further, PLE (hazard ratio [HR]: 14.4), left isomerism (HR: 3.5),
      and NYHA (HR: 2.4) independently predicted a high 5-year high mortality (p < 0.05
      for all). The incidence of cancer-related mortality increased markedly with age
      >40 years. CONCLUSIONS: Majority of the Japanese adult Fontan survivors had good
      functional status, with an acceptable 5-year survival rate. However, the
      significant prevalence of non-cardiac mortality highlights Fontan pathophysiology
      as a multi-organ disease that requires a multidisciplinary management strategy to
      improve the long-term outcome.

PMID- 30201382
TI  - Real-world outcomes in patients with metastatic castration-resistant prostate
      cancer receiving second-line chemotherapy versus an alternative androgen receptor
      targeted agent (ARTA) following early progression on a first-line ARTA in a US
      community oncology setting.
AB  - OBJECTIVE: This retrospective observational study assessed if second-line
      chemotherapy vs. androgen receptor-targeted agents (ARTAs;
      abiraterone/enzalutamide) is associated with improved outcomes in metastatic
      castration-resistant prostate cancer (mCRCaP) patients who experience early
      progression on first-line ARTAs in a US community setting. METHODS: Patients with
      mCRCaP (n = 345) who progressed <= 12 months after first-line ARTA and received
      second-line chemotherapy (docetaxel/cabazitaxel; n = 147) or ARTA (n = 198)
      between May 2011 and October 2014 were identified. Overall survival (OS),
      prostate-specific antigen (PSA) response and progression, and clinical response
      were compared for second-line chemotherapy vs. ARTA, using one-sided tests from
      second-line therapy initiation. Multivariate analyses were adjusted for: year,
      age, metastases, opioid use, Eastern Cooperative Oncology Group performance
      score, PSA, hemoglobin, alkaline phosphatase, lactate dehydrogenase (LDH), and
      albumin levels. RESULTS: Patients receiving second-line chemotherapy vs. ARTA
      were younger (median: 74 vs. 79 years) and had a poorer prognosis in terms of
      PSA, LDH, alkaline phosphatase, albumin and hemoglobin levels, opioid use, and
      Halabi risk score (P < 0.05). Response rates were higher for chemotherapy vs.
      ARTA (PSA: adjusted odds ratio = 2.27, P = 0.005; clinical: adjusted odds ratio =
      1.78; P = 0.020) and time to PSA progression was longer (adjusted hazard ratio
      [aHR] = 0.66; P = 0.010). A trend favored chemotherapy vs. ARTA for OS (aHR =
      0.81, P = 0.148). Among patients with poor prognostic features, those receiving
      chemotherapy had significantly improved OS (Halabi intermediate-/high-risk score:
      aHR = 0.55, P = 0.009; hemoglobin < 11 g/dl: aHR = 0.41, P = 0.002; LDH > upper
      limit of normal: aHR = 0.18, P = 0.014; albumin < lower limit of normal: aHR =
      0.42, P = 0.020). CONCLUSION: Following early progression on first-line ARTA,
      second-line chemotherapy may be more beneficial in mCRCaP compared with second
      line ARTA in patients with a poor prognosis.

PMID- 30201383
TI  - The peripheral eye: A neurogenic area with potential to treat retinal
      pathologies?
AB  - Numerous degenerative diseases affecting visual function, including glaucoma and
      retinitis pigmentosa, are produced by the loss of different types of retinal
      cells. Cell replacement therapy has emerged as a promising strategy for treating
      these and other retinal diseases. The retinal margin or ciliary body (CB) of
      mammals has been proposed as a potential source of cells to be used in
      degenerative conditions affecting the retina because it has been reported it
      might hold neurogenic potential beyond embryonic development. However, many
      aspects of the origin and biology of the CB are unknown and more recent
      experiments have challenged the capacity of CB cells to generate different types
      of retinal neurons. Here we review the most recent findings about the development
      of the marginal zone of the retina in different vertebrates and some of the
      mechanisms underlying the proliferative and neurogenic capacity of this
      fascinating region of the vertebrates eye. In addition, we performed experiments
      to isolate CB cells from the mouse retina, generated neurospheres and observed
      that they can be expanded with a proliferative ratio similar to neural stem
      cells. When induced to differentiate, cells derived from the CB neurospheres
      start to express early neural markers but, unlike embryonic stem cells, they are
      not able to fully differentiate in vitro or generate retinal organoids. Together
      with previous reports on the neurogenic capacity of CB cells, also reviewed here,
      our results contribute to the current knowledge about the potentiality of this
      peripheral region of the eye as a therapeutic source of functional retinal
      neurons in degenerative diseases.

PMID- 30201384
TI  - A sensitive and improved throughput UPLC-MS/MS quantitation method of total
      cytochrome P450 mediated arachidonic acid metabolites that can separate regio
      isomers and cis/trans-EETs from human plasma.
AB  - A method for the detection and quantification of hydroxyl and epoxy arachidonic
      acid (AA) metabolites in human plasma was developed using liquid-liquid
      extraction, phospholipid saponification followed by derivatization of the acid
      moiety and liquid chromatographic tandem mass spectrometric detection.
      Derivatization with a pyridinium analog allowed for detection in the positive ion
      mode, greatly improving sensitivity and the stability of the more labile AA
      metabolites. The entire method utilizes a 96-well plate format, increasing sample
      throughput, and was optimized to measure 5-, 8-, 9-, 11-, 12-, 15-, 19-, and 20-
      hydroxyeicosatetraenoic acid (HETE), 5,6-, 8,9-, 11,12-, and 14,15-
      dihydroxyeicosatrienoic acid (DHET), and the regio- and cis-/ trans- isomers of
      5,6-, 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid (EET). The method was
      validated for its applicability over the FA concentration range found in human
      plasma. Using 100 MUL aliquots of pooled human plasma, EET levels, particularly
      5,6-EET, were observed to be higher than previously reported, with measured
      concentrations of 23.6 ng/ml for 5,6-EET, 5.6 ng/mL for 5,6-trans-EET, 8.0 ng/mL
      for 8,9-EET, 1.9 ng/mL for 8,9-trans-EET, 8.8 ng/mL for 11,12-EET, 3.4 ng/mL for
      11,12-trans-EET, 10.7 ng/mL for 14,15-EET, and 1.7 ng/mL 14,15-trans- EET. This
      method is suitable for large population studies to elucidate the complex
      interactions between the eicosanoids and various disease states and may be used
      for quantitation of a wide variety of fattyacids beyond eicosanoids from small
      volumes of human plasma.

PMID- 30201385
TI  - Now is the time for (2R,6R)-hydroxynorketamine to be viewed independently from
      its parent drug.

PMID- 30201387
TI  - Protective effects of Devosia sp. ANSB714 on growth performance, immunity
      function, antioxidant capacity and tissue residues in growing-finishing pigs fed
      with deoxynivalenol contaminated diets.
AB  - This study aimed to investigate the toxic effects of deoxynivalenol (DON) and the
      effectiveness of Devosia sp. ANSB714 for alleviation of DON toxicosis in growing
      finishing pigs. A total of twenty pigs were allocated equally to four treatments
      for 18 days: CON (basal diet formulated with normal rice), Devosia sp. ANSB714
      (CON + Devosia sp. ANSB714), DON (toxic diet formulated with DON-contaminated
      rice), and DON + Devosia sp. ANSB714. The treatments of Devosia sp. ANSB714 and
      DON + Devosia sp. ANSB714 were given the fermentation liquor of Devosia sp
      ANSB714 by drinking water. DON-contaminated diet significantly decreased the
      average daily gain of growing-finishing pigs. Serum IgA content was significantly
      increased in DON treatment compared with that in CON. Besides, DON in diet also
      significantly reduced the activities of GSH-Px in the liver and serum of pigs.
      Supplementation of Devosia sp. ANSB714 in drinking water effectively prevented
      these adverse effects of DON on pigs. Moreover, the DON residues in the serum,
      liver and kidney were significantly decreased with the addition of Devosia sp.
      ANSB714 to diet contaminated with DON. Taken together, it is effective to feeding
      Devosia sp. ANSB714 to pigs fed with diet contaminated with DON and ameliorating
      DON toxicosis of pigs.

PMID- 30201388
TI  - "How similar is similar enough? A sufficient similarity case study with Ginkgo
      biloba extract" by Catlin et al.; Food and Chemical Toxicology 118 (2018) 328
      339.

PMID- 30201386
TI  - Menthol facilitates dopamine-releasing effect of nicotine in rat nucleus
      accumbens.
AB  - Menthol is a significant flavoring additive in tobacco products. Accumulating
      clinical evidence suggests that menthol may promote tobacco smoking and nicotine
      dependence. Our previous studies demonstrated that menthol enhanced nicotine
      reinforcement in rats. However, it is unclear whether menthol interacts with
      nicotine at the neurochemical level. The present study used intracranial
      microdialysis to examine whether and the ways in which menthol affects nicotine
      induced dopamine release in rats in the nucleus accumbens core (NAc), a terminal
      field of brain reward circuitry. To make comparisons with our previous work that
      showed an enhancing effect of menthol on nicotine self-administration behavior,
      male Sprague-Dawley rats were first trained in 20 daily 1-h sessions to press a
      lever for intravenous nicotine self-administration (15 MUg/kg/infusion). Dopamine
      levels were then measured in the right NAc using intracranial microdialysis
      coupled with high-performance liquid chromatography. Five minutes before
      microdialysis, the rats received an intraperitoneal injection of menthol (0, 1,
      2.5, and 5 mg/kg), a subcutaneous injection of nicotine (0.2 mg/kg or its
      vehicle), or both. Menthol alone did not affect dopamine levels in dialysates,
      whereas nicotine alone elevated dopamine levels. Combined nicotine and menthol
      administration significantly increased dopamine levels compared with nicotine
      alone. These data indicate a facilitating effect of menthol on nicotine-induced
      dopamine release in the NAc. These findings shed light on our understanding of
      the neurobiological mechanisms that underlie the menthol-induced enhancement of
      nicotine reinforcement.

PMID- 30201389
TI  - RIFM fragrance ingredient safety assessment, terpinyl propionate, CAS Registry
      Number 80-27-3.

PMID- 30201390
TI  - Activation of the ventral subiculum reinvigorates behavior after failure to
      achieve a goal: Implications for dopaminergic modulation of motivational
      processes.
AB  - Previous studies confirm that brief electrical stimulation of glutamatergic
      afferents from the ventral subiculum (vSub) can significantly enhance dopamine
      release in the ventral striatum for an extended duration (>20 min). However, the
      functional significance of this effect on motivated behavior remains to be
      specified. Here we tested the hypothesis that brief electrical stimulation of the
      ventral subiculum (20 Hz for 10 s) might increase effort expenditure for food
      rewards. Motivation was assessed by a progressive ratio lever pressing task,
      which requires continuous escalation of the numbers of lever presses to receive
      each subsequent sucrose pellet, eventually resulting in the failure to achieve
      the required ratio for a food reward. vSub stimulation at the start of a session
      did not affect the rate or total number of lever presses prior to reaching the
      "break point". In contrast, stimulation of the vSub with identical parameters on
      a post break point trial resulted in a significant increase in total responses.
      These findings demonstrate that activation of the vSub with parameters that
      modulate dopamine efflux in the nucleus accumbens can re-activate goal-directed
      behavior after failure to achieve a goal. Our data highlight a possible role for
      the vSub in the pathophysiology and potential treatment of motivational processes
      linked to psychiatric disease.

PMID- 30201391
TI  - Evaluation of LIPS (luciferase immunoprecipitation system) for serodiagnosis of
      Toxoplasmosis.
AB  - Development of reliable, quantitative technologies for serodiagnosis of
      Toxoplasma gondii infection remains desirable. The luciferase immunoprecipitation
      system (LIPS) is a relatively simple, highly sensitive, and rapid quantitative
      immunoassay. The major advantages of this assay over ELISA are a wider dynamic
      range, shorter overall assay time, and less sample volume. In this study, we
      aimed to use this method for the serodiagnosis of toxoplasmosis. Recombinant
      Toxoplasma antigens (dense granule antigens GRA6, GRA7, and GRA8 and bradyzoite
      antigen BAG1) fused with nanoluciferase (Nluc, a small luciferase enzyme) were
      expressed in Escherichia coli, purified, and tested in LIPS assays with sera from
      experimental mice infected with T. gondii and a WHO standard anti-Toxoplasma
      human immunoglobulin (TOXM). In the experimentally infected mice, LIPS assays
      detected antibodies against Nluc-GRA6, Nluc-GRA7, and Nluc-GRA8 as early as day
      14, whereas antibodies against Nluc-BAG1 remained undetected until day 21 and
      then showed significant elevation on day 60. In TOXM sera, LIPS assays with each
      Nluc recombinant protein produced reliable standard curves with a coefficient of
      determination (R2) of 0.980-0.989 for GRA6, 0.986-0.990 for GRA7, 0.998-0.999 for
      GRA8, and 0.942-0.987 for BAG1. The detection limits were estimated to be 3.9, 2,
      1, and 1 IU/ml for rGRA6, rGRA7, rGRA8, and rBAG1, respectively. The LIPS assay
      for toxoplasmosis could detect antibodies against T. gondii in the mouse and
      human sera with a reasonably high sensitivity. We consider the LIPS assay to be a
      promising alternative tool for screening, diagnosing, and monitoring
      toxoplasmosis. In particular, detection of antibodies against BAG1 may be useful
      for a longitudinal seroprevalence study in suspected high-risk areas on the basis
      of its elevated serum concentration in the chronic phase.

PMID- 30201392
TI  - CD4+ T cell activation, function, and metabolism are inhibited by low
      concentrations of DMSO.
AB  - Dimethyl sulfoxide (DMSO) is a polar organic solvent used in a wide range of
      biological applications. DMSO is routinely used as a cryoprotectant for long-term
      cell freezing as well as to dissolve peptides and drugs for immune cell
      functional assays. Here, human CD4+ T cell activation, cytokine production,
      proliferation, and metabolism were investigated after stimulation in the presence
      of 0.01% to 1%, DMSO, representing concentrations commonly used in vitro. Surface
      expression of the activation markers CD69, CD25 and CD154 after polyclonal
      activation of CD4+ T cells was inhibited by 0.25% or higher concentrations of
      DMSO. The frequencies of IL-21+, IL-4+, and IL-22+ CD4+ T cells, following
      polyclonal activation were variably inhibited by DMSO at concentrations ranging
      from 0.25% to 1%, whereas IFNgamma+ cells were unaffected. CD4+ T cell
      proliferation after anti-CD3 or antigen stimulation was inhibited by 0.5% DMSO
      and abolished by 1% DMSO. After polyclonal stimulation, glucose uptake was
      inhibited in the presence of 1% DMSO, but only minor effects on CD4+ T cell
      respiration were observed. Consistent with the immune effects, the gene
      expression of early signaling and activation pathways were inhibited in CD4+ T
      cells in the presence of 1% DMSO. Our study revealed that DMSO at concentrations
      generally used for in vitro studies of T cells impacts multiple features of T
      cell function. Therefore, we urge care when adding DMSO-containing preparations
      to T cell cultures.

PMID- 30201393
TI  - Additional Stability Testing of Cryopreserved Intestinal Biopsies for Downstream
      Flow Cytometric Analysis.

PMID- 30201394
TI  - A new look at painful diabetic neuropathy.
AB  - The prevalence of diabetes mellitus and its chronic complications continue to
      increase alarmingly. Consequently, the massive expenditure on diabetic distal
      symmetrical polyneuropathy (DSPN) and its sequelae, will also likely rise. Up to
      50% of patients with diabetes develop DSPN, and about 20% develop neuropathic
      pain (painful-DSPN). Painful-DSPN can cast a huge burden on sufferers' lives with
      increased rates of unemployment, mental health disorders and physical co
      morbidities. Unfortunately, due to limited understanding of the mechanisms
      leading to painful-DSPN, current treatments remain inadequate. Recent studies
      examining the pathophysiology of painful-DSPN have identified maladaptive
      alterations at the level of both the peripheral and central nervous systems.
      Additionally, genetic studies have suggested that patients with variants of
      voltage gated sodium channels may be more at risk of developing neuropathic pain
      in the presence of a disease trigger such as diabetes. We review the recent
      advances in genetics, skin biopsy immunohistochemistry and neuro-imaging, which
      have the potential to further our understanding of the condition, and identify
      targets for new mechanism based therapies.

PMID- 30201395
TI  - Perspectives on diagnostic strategies for HIP-dealing with the barriers and
      challenges: USA.
AB  - BACKGROUND: Gestational diabetes (GDM) affects up to 7-18% of pregnant women and
      is associated with several maternal and perinatal morbidities. International
      organizations suggest several different recommendations regarding how to screen
      and to manage hyperglycemia in pregnancy (HIP). OBJECTIVE: We aimed to analyze
      the most important and employed guidelines about screening and management of HIP
      and we investigated existing related literature. RESULTS: We found several
      different criteria for screening for HIP, with the main difference being between
      non-USA-based IADPSG (One-step) approach, and the USA-based (Two-step) approach.
      The use of IADPSG approach (One-step) is associated with an increase in the
      incidence of GDM, improvement of several maternal and perinatal outcomes, and
      cost-effectiveness, compared to the USA-based Two-step criteria. CONCLUSIONS: As
      the One-Step approach endorsed by IADPSG, WHO, and FIGO is associated with
      maternal and perinatal benefits, it should be preferred to the Two-Step approach
      currently endorsed by the USA-based societies such as ACOG and SMFM. The hope is
      to approve universal screening guidelines based on the One-step approach to
      improve health care and reduce costs and adverse outcomes for women with GDM.

PMID- 30201396
TI  - CpAMs induce assembly of HBV capsids with altered electrophoresis mobility:
      Implications for mechanism of inhibiting pgRNA packaging.
AB  - Native agarose gel electrophoresis-based particle gel assay has been commonly
      used for examination of hepatitis B virus (HBV) capsid assembly and pregenomic
      RNA encapsidation in HBV replicating cells. Interestingly, treatment of cells
      with several chemotypes of HBV core protein allosteric modulators (CpAMs) induced
      the assembly of both empty and DNA-containing capsids with faster electrophoresis
      mobility. In an effort to determine the physical basis of CpAM-induced capsid
      mobility shift, we found that the surface charge, but not the size, of capsids is
      the primary determinant of electrophoresis mobility. Specifically, through
      alanine scanning mutagenesis analysis of twenty-seven charged amino acids in core
      protein assembly domain and hinge region, we showed that except for K7 and E8,
      substitution of glutamine acid (E) or aspartic acid (D) on the surface of capsids
      reduced their mobility, but substitution of lysine (K) or arginine (R) on the
      surface of capsids increased their mobility in variable degrees. However, alanine
      substitution of the charged amino acids that are not exposed on the surface of
      capsid did not apparently alter capsid mobility. Hence, CpAM-induced
      electrophoresis mobility shift of capsids may reflect the global alteration of
      capsid structure that changes the exposure and/or ionization of charged amino
      acid side chains of core protein. Our findings imply that CpAM inhibition of
      pgRNA encapsidation is possibly due to the assembly of structurally altered
      nucleocapsids. Practically, capsid electrophoresis mobility shift is a diagnostic
      marker of compounds that target core protein assembly and predicts sensitivity of
      HBV strains to specific CpAMs.

PMID- 30201397
TI  - Ruxolitinib as Salvage Therapy for Chronic Graft-versus-Host Disease.
AB  - Chronic graft-versus-host disease (cGVHD) continues to be a major complication
      after allogeneic hematopoietic cell transplantation, significantly affecting
      patients' quality of life. A regimen of systemic corticosteroids is considered
      first-line therapy but is often associated with inadequate responses and multiple
      side effects. In patients with refractory disease, an evidenced-based consensus
      is lacking as to the single best approach to managing symptoms. Ruxolitinib, a
      selective JAK1/2 inhibitor, has recently gained favor as a second-line approach
      in patients with steroid-refractory cGVHD. In this retrospective study, we
      evaluated the outcomes of 46 patients who received ruxolitinib for cGVHD between
      March 2016 and December 2017 at our institution, and evaluated ruxolitinib's
      impact at 6 and 12 months, based on the National Institutes of Health Severity
      Scale, including organ-specific responses, and mean prednisone dose. Furthermore,
      we present the first reported probability of ruxolitinib's treatment failure-free
      survival (FFS) in patients with cGVHD. After 12 months of ruxolitinib therapy,
      complete response, partial response, and stable disease was observed in 13% (n =
      6), 30.4% (n = 14), and 10.9% (n = 5) of patients, respectively. The 1-year
      probability of FFS was 54.2% (95% confidence interval, .388 to .673), and
      ruxolitinib use was associated with a reduction in prednisone dose. In
      conclusion, our data, which represent the largest cohort of patients with cGVHD
      reported to date, support the use of ruxolitinib for cGVHD refractory to steroids
      and currently available salvage therapies, discontinued due to lack of response
      and high cost.

PMID- 30201398
TI  - Impact of preoperative biopsy sampling on severe submucosal fibrosis on
      endoscopic submucosal dissection for colorectal laterally spreading tumors: a
      propensity score analysis.
AB  - BACKGROUND AND AIMS: It is believed that preoperative biopsy sampling for
      superficial-type colorectal tumors should be avoided because submucosal fibrosis
      caused by biopsy sampling makes EMR impossible. However, few studies have
      reported the influence of biopsy sampling on colorectal endoscopic submucosal
      dissection (ESD). This study aimed to examine the effect of biopsy sampling on
      submucosal fibrosis and treatment outcomes of ESD for laterally spreading tumors
      (LSTs). METHODS: Between April 2005 and September 2015, 441 consecutive patients
      underwent colorectal ESD in Osaka City University Hospital. Using propensity
      score matching and inverse probability of treatment weighting (IPTW), we
      retrospectively evaluated risk factors for severe submucosal fibrosis and
      treatment outcomes for patients with LSTs, with or without preoperative biopsy
      sampling. RESULTS: A total of 428 LSTs resected using ESD were enrolled. After
      matching, there were 136 matched pairs of lesions that did or did not undergo
      biopsy sampling. Preoperative biopsy sampling increased severe fibrosis compared
      with that in the non-biopsy sampling group (20.6% vs 11.0%; P = .03) and was
      significantly associated with severe fibrosis after matching (odds ratio [OR],
      2.09; 95% confidence interval [CI], 1.07-4.10; P = .03). After adjustment with
      IPTW, biopsy sampling also increased the risk of severe fibrosis (OR, 2.33; 95%
      CI, 1.17-4.63; P = .02). However, no significant differences were observed
      between the 2 groups in treatment outcomes. CONCLUSIONS: Preoperative biopsy
      sampling for colorectal LSTs might cause severe submucosal fibrosis but has no
      adverse influence on clinical outcomes of ESD.

PMID- 30201399
TI  - [Follow-up and evaluation of plans developed during pulmonary rehabilitation].
AB  - BACKGROUND: Pulmonary rehabilitation inevitably contains two essential
      components: therapeutic education and exercise training. The principal aim of
      this study was to evaluate the evolution over a year of the realization of plans
      determined during a pulmonary rehabilitation program (PRP). METHODS: At the end
      of a PRP the patient made plans in accordance with his health condition. A
      telephone enquiry was undertaken at 3, 7 and 12 months to evaluate the progress
      of the plans, the motivation to perform them, dyspnoea and quality of life.
      RESULTS: The data of 65 patients were analyzed (87 inclusions). Fifty-seven
      percent of the plans continued for one year. Walking had an adherence rating of
      71%. Loss of motivation appeared to be the main cause for stopping (20%). Quality
      of life remained stable (p=0.39) and an increase in dyspnoea, though
      statistically significant (p<0.01), was of no clinical relevance. CONCLUSION: The
      majority of plans were maintained but without clinical effect on the quality of
      life or the level of dyspnoea. Decreased motivation was the major limitation to
      realization or continuation of the plans. New studies will have to be implemented
      to analyze the factors which lead to this decrease.

PMID- 30201400
TI  - Heterologous expression and purification of a marine alginate lyase in
      Escherichia coli.
AB  - Alginate lyase digestion is an efficient way to degrade alginate into
      oligosaccharides, which are useful in various areas including chemistry, pharmacy
      and food industry. Here we determined the sequence of Vibrio sp. QY102 sourced
      alginate lyase, and set up its heterologous expression in E. coli. We improved
      its secretion efficiency by replacing the original secretive sequence by E. coli
      specific signal peptide ompA. We successfully purified the full-length protein in
      shake flask culture, however, degradation happened during fed batch cultivation.
      By domain and disorder examination, we found that the protein was completely
      functional by expressing the C terminal fragment alone. For the final strain we
      constructed (HMS-ompA-CF), the extracellular enzyme activity reached 375 U/ml in
      shake flask and 1789 U/ml in fed batch cultivation (5 L bioreactor). And the
      final protein yield reached 0.58 g/L in fed batch cultivation. We determined that
      the optimal pH and temperature for the shortened alginate lyase were 7.0 and 39 
      degrees C, respectively.

PMID- 30201402
TI  - Feasibility of Biventricular Intracorporeal Ventricular Assist in a Pediatric
      Patient.

PMID- 30201403
TI  - 1-Naphthyl acetate: A chromogenic substrate for the detection of erythrocyte
      acetylcholinesterase activity.
AB  - Erythrocyte acetylcholinesterase (AChE) is a preferred biomarker for the
      detection of organophosphorus poisoning. Acetylthiocholine (ATCh) is the most
      popular substrate for the detection of AChE activity. However, oximolysis is a
      prominent feature with ATCh. In this context, we have searched alternative
      substrates for AChE using in silico tools for screening of a better substrate.
      The in silico approach was performed to understand the fitness and the Total
      Interaction Energy (TIE) of substrates for AChE. The alternative substrates for
      AChE were screened in terms of high Goldscore and favorable TIE in comparison to
      acetylcholine (ACh)-AChE complex and other relevant esterases. Among the screened
      substrates, 1-Naphthyl acetate (1-NA) exhibited the most favorable interaction
      with AChE in terms of highest TIE and corresponding high Goldscore. The Molecular
      Dynamic (MD) simulation of the 1-NA-AChE complex showed a stable complex
      formation over a period of 5 ns. The results obtained in the in silico studies
      were validated in vitro using pure erythrocyte AChE and hemolysate. We observed 1
      NA to be a better alternative substrate for AChE than ATCh in terms of lower Km
      value. Its specificity appeared at least similar to ATCh. Therefore, we propose
      that 1-NA can be an attractive chromogenic substrate for the measurement of AChE
      activity, and it possess the potential to detect organophosphorus pesticide (OP)
      poisoning.

PMID- 30201404
TI  - Red Blood Cell Disorders: Perioperative Considerations for Patients Undergoing
      Cardiac Surgery.
AB  - Disorders affecting red blood cells (RBCs) are uncommon yet have many important
      physiologic considerations for patients undergoing cardiac surgery. RBC disorders
      can be categorized by those that are congenital or acquired, and further by
      disorders affecting the RBC membrane, hemoglobin, intracellular enzymes, or
      excessive RBC production. A foundational understanding of the physiologic
      derangement for these disorders is critical when considering perioperative
      implications and optimization, strategies for cardiopulmonary bypass, and the
      rapid recognition and treatment if complications occur. This review
      systematically outlines the RBC disorders of frequency and relevance with an
      emphasis on how the disorder affects normal physiologic processes, a review of
      the literature related to the disorder, and the implications and recommendations
      for patients undergoing cardiac surgery.

PMID- 30201401
TI  - The development of the error-related negativity in large sample of adolescent
      females: Associations with anxiety symptoms.
AB  - Anxiety is the most common form of psychopathology and tends to begin early in
      the course of development. Given this, there is great interest in identifying
      developmental changes in neural systems that may delineate healthy versus anxious
      trajectories. A substantial amount of work has focused on the error-related
      negativity as a neural marker of anxiety. The ERN is a negative deflection in the
      event-related potential that occurs when individuals make mistakes and is
      increased in anxious individuals. A separate body of work has focused on
      normative developmental changes in the ERN - demonstrating an age-related
      increase in the ERN that occurs across childhood and adolescence. In the current
      study, we examine the ERN in relation to specific phenotypic expressions of
      anxiety during a core risk period in a sample of females (N = 220) ranging from 8
      to 14 years old. Results from the current study suggest that error-related brain
      activity is related to both parent and child report of social anxiety symptoms,
      even when controlling for all other symptom scales. Additionally, mediation
      models suggest that the normative developmental increase observed in the ERN is
      partially mediated by increases in social anxiety symptoms. The current results
      are novel insofar as they identify a specific phenotypic expression of anxiety
      that underlies developmental increases in this neural biomarker.

PMID- 30201405
TI  - Oxygen-dependent distinct expression of hif-1alpha gene in aerobic and anaerobic
      tissues of the Amazon Oscar, Astronotus crassipinnis.
AB  - The aquatic habitats of the Amazon basin present dramatic variation of oxygen
      level, and, to survive such changes, many aquatic animals developed biochemical
      and physiological adaptations. The advanced teleost Astronotus crassipinnis
      (Perciformes) is a fish tolerant to hypoxia and known to endure such naturally
      variable environments. Hypoxia-Inducible factor-1alpha (hif-1alpha) is among the
      most important and studied genes related to hypoxia-tolerance, maintaining
      regular cellular function and controlling anaerobic metabolism. In the present
      work, we studied hif-1alpha expression and related it to changes in metabolic
      pathways of Astronotus crassipinnis exposed to 1, 3 and 5 h of hypoxia, followed
      by 3 h of recovery. The results show that A. crassipinnis depresses aerobic
      metabolic under hypoxia, with a decrease in glycolysis and oxidative enzyme
      activities, and increases its anaerobic metabolism with an increase in LDH
      activity coupled with a decrease in oxygen consumption, which indicates an
      increase in anaerobic capacity. In addition, the animal differentially regulates
      hif-1alpha gene in each tissue studied, with a positive relationship to its
      metabolic profile, suggesting that hif-1alpha might be one of the most important
      induction factors that regulate hypoxia tolerance in this species.

PMID- 30201406
TI  - Health-care Cost Impact of Continued Anticoagulation With Rivaroxaban vs Aspirin
      for Prevention of Recurrent Symptomatic VTE in the EINSTEIN-CHOICE Trial
      Population.
AB  - BACKGROUND: Using data from the Reduced-Dose Rivaroxaban in the Long-Term
      Prevention of Recurrent Symptomatic Venous Thromboembolism (EINSTEIN-CHOICE)
      trial, this study assessed cost impact of continued anticoagulation therapy with
      rivaroxaban vs aspirin. METHODS: Total health-care costs (2016 USD) associated
      with rivaroxaban and aspirin were calculated as the sum of clinical event costs
      and drug costs from a US managed care perspective. Clinical event costs were
      calculated by multiplying event rate by cost of care. One-year Kaplan-Meier
      clinical event rates for recurrent pulmonary embolism, recurrent DVT, all-cause
      mortality, and bleeding were obtained from EINSTEIN-CHOICE. Cost of care was
      determined by literature review. Drug costs were the product of drug price
      (wholesale acquisition cost) and treatment duration. A one-way sensitivity
      analysis was conducted. RESULTS: Rivaroxaban users had lower per patient per
      month (PPPM) clinical event costs compared with aspirin users ($123, $243, and
      $381 for rivaroxaban 10 mg, rivaroxaban 20 mg, and aspirin, respectively).
      However, vs aspirin, PPPM total health-care costs were $24 higher for patients
      treated with rivaroxaban 10 mg ($143 higher for rivaroxaban 20 mg) due to higher
      cost of rivaroxaban. With a 15% discount for rivaroxaban 10 mg, the lower cost of
      clinical events for the rivaroxaban-treated patients more than fully offset the
      higher drug costs, and yielded a $19 lower total health-care cost. CONCLUSIONS:
      Continued therapy with rivaroxaban 10 and 20 mg vs aspirin was associated with
      lower clinical event costs but higher total health-care costs; with a 15% drug
      discount rivaroxaban 10 mg had lower total health-care costs than aspirin.

PMID- 30201407
TI  - Cutaneous Complications in Recipients of Lung Transplants: A Pictorial Review.
AB  - Lung transplant is now an established modality for a broad spectrum of end-stage
      pulmonary diseases. According to the International Society for Heart and Lung
      Transplantation Registry, more than 50,000 lung transplants have been performed
      worldwide, with nearly 11,000 recipients of lung transplants alive in the United
      States. With the increasing use of lung transplant, pulmonologists must be
      cognizant of the common as well as the unique posttransplant dermatologic
      complications. Immunosuppression, infections, and a variety of medications and
      environmental exposures can contribute to these complications. This review aims
      to provide representative pictures and describe the pathogenesis, epidemiologic
      characteristics, and clinical manifestations of dermatologic complications
      encountered among recipients of lung transplants.

PMID- 30201408
TI  - Randomized, Double-Blind, Placebo-Controlled, Phase 2 Trial of BMS-986020, a
      Lysophosphatidic Acid Receptor Antagonist for the Treatment of Idiopathic
      Pulmonary Fibrosis.
AB  - BACKGROUND: Idiopathic pulmonary fibrosis (IPF) causes irreversible loss of lung
      function. The lysophosphatidic acid receptor 1 (LPA1) pathway is implicated in
      IPF etiology. Safety and efficacy of BMS-986020, a high-affinity LPA1 antagonist,
      was assessed vs placebo in a phase 2 study in patients with IPF. METHODS:
      IM136003 was a phase 2, parallel-arm, multicenter, randomized, double-blind,
      placebo-controlled trial. Adults with IPF (FVC, 45%-90%; diffusing capacity for
      carbon monoxide, 30%-80%) were randomized to receive placebo or 600 mg BMS-986020
      (once daily [qd] or bid) for 26 weeks. The primary end point was rate of change
      in FVC from baseline to week 26. RESULTS: Of 143 randomized patients, 108
      completed the 26-week dosing phase. Thirty-five patients discontinued
      prematurely. Patient baseline characteristics were similar between treatment
      groups (placebo: n = 47; 600 mg qd: n = 48; 600 mg bid: n = 48). Patients treated
      with BMS-986020 bid experienced a significantly slower rate of decline in FVC vs
      placebo (-0.042 L; 95% CI, -0.106 to -0.022 vs -0.134 L; 95% CI, -0.201 to 
      0.068, respectively; P = .049). Dose-related elevations in hepatic enzymes were
      observed in both BMS-986020 treatment groups. The study was terminated early
      because of three cases of cholecystitis that were determined to be related to BMS
      986020 after unblinding. CONCLUSIONS: BMS-986020 600 mg bid treatment for 26
      weeks vs placebo significantly slowed the rate of FVC decline. Both regimens of
      BMS-986020 were associated with elevations in hepatic enzymes. TRIAL REGISTRY:
      ClinicalTrials.gov; No.: NCT01766817; URL: www.clinicaltrials.gov.

PMID- 30201409
TI  - Pharmacologic targeting of the ATX/LPA axis attenuates bleomycin-induced
      pulmonary fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing lung disease with a
      dismal prognosis and a largely unknown etiology. Autotaxin (ATX) is a secreted
      lysophospholipase D, largely responsible for extracellular production of
      lysophosphatidic acid (LPA), a bioactive phospholipid. LPA has numerous effects
      in most cell types, signaling through at least 6 receptors (LPAR) exhibiting wide
      spread distribution and overlapping specificities. The ATX/LPA axis has been
      suggested as a therapeutic target in different chronic inflammatory and
      fibroproliferative disorders, including pulmonary fibrosis. In this report, we
      examined head-to-head the efficacy of a potent inhibitor of ATX (PF-8380), that
      has not been tested in pulmonary fibrosis models, and an antagonist of LPAR1
      (AM095) in bleomycin (BLM)-induced pulmonary fibrosis. Both compounds abrogated
      the development of pulmonary fibrosis and prevented the distortion of lung
      architecture, exhibiting qualitative and quantitative differences in different
      manifestations of the modeled disease.

PMID- 30201410
TI  - Development of a novel digital breath-activated inhaler: Initial particle size
      characterization and clinical testing.
AB  - BACKGROUND: Delivery of inhaled respiratory medications have been associated with
      variable delivery of drug due to errors in device operations and have not been
      designed to monitor true delivery of medication. A fully digital breath-activated
      inhaled (DBAI) delivery platform has been developed with integrated firmware and
      software to address these limitations. METHODS: the device was designed to
      produce similar aerosol particle output to a marketed albuterol MDI and to the
      albuterol/ipratropium combination in a soft mist inhaler (SMI). Cascade impactor
      studies were conducted to demonstrate comparable aerodynamic particle size
      distribution (APSD) metrics. Efficacy was evaluated by pharmacodynamic studies
      involving spirometry in two separate protocols with adult subjects having COPD
      (albuterol DBAI vs. albuterol MDI - Study A, albuterol/ipratropium DBAI single
      arm - Study B). RESULTS: The total emitted doses (TED) were 81.9 +/- 10.3, 109.3
      +/- 15.0 and 121.9 +/- 7.0 MUg/actuation for the DBAI, SMI and MDI respectively,
      and the fine (respirable) particle doses (FPD) were 56.2 +/- 6.0, 61.7 +/- 5.5
      and 79.4 +/- 2.7 MUg/actuation. MMADs for albuterol sulfate were 1.93 +/- 0.11,
      1.75 +/- 0.19, and 2.65 +/- 0.05 MUm for the DBAI, Respimat soft mist inhaler
      (SMI) and MDI respectively. The corresponding GSDs were 1.96 +/- 0.16, 2.79 +/-
      0.25, and 1.48 +/- 0.02 MUm. The corresponding respirable fractions were 68.7 +/-
      3.2%, 57.3 +/- 10.5%, and 65.2 +/- 2.4%. Spirometric study A enrolled 23 subjects
      (age 64 +/- 7.3 years, 39% male, FEV1 45 +/- 14% predicted). Study B enrolled 23
      subjects (age 65 +/- 8.6 years, 43% male, FEV1 47 +/- 10% predicted). For Study
      A, FEV1 at 20 min post-dose improved by 120 (167) mL (p = 0.002) for the DBAI
      device and 109 (183) mL (p = 0.008) for the MDI device (p = 0.86 for between
      group differences). For Study B, FEV1 (20 min post-dose) improved by 216 (126) mL
      (p < 0.001). CONCLUSION: The DBAI generated highly respirable aerosols containing
      albuterol sulfate that were similar to the MDI and SMI in respirable fraction but
      lower in dose. Subsequent pharmacodynamic studies delivering albuterol sulfate
      alone and in combination with ipratropium bromide confirmed similar responses for
      the DBAI compared with the other inhalers, which could possibly be related to a
      response ceiling. The DBAI breath-activated capability combined with the ability
      to monitor actual delivery of medication may improve effectiveness by overcoming
      patient miscoordination.

PMID- 30201411
TI  - IL-37b suppresses epithelial mesenchymal transition in hepatocellular carcinoma
      by inhibiting IL-6/STAT3 signaling.
AB  - BACKGROUND: Interleukin-37b (IL-37b), a vital negative regulator of the innate
      immune system, has been reported to be a tumor inhibitor in different type of
      cancers. However, little is known about the relationship between IL-37b and
      hepatocellular carcinoma (HCC). The present study aimed to investigate the
      potential roles of IL-37b in HCC progression. METHODS: Subjects (n = 237) were
      recruited, and serum IL-37b was measured using ELISA. The tumor-suppressive
      capacity and underlying mechanisms of IL-37b in HCC were investigated in vitro
      and in vivo. RESULTS: Compared to healthy controls, serum IL-37b levels were
      elevated in chronic hepatitis B (CHB) patients but decreased significantly in HBV
      HCC patients, especially for those with portal venous tumor thrombus. Low level
      serum IL-37b in HBV-HCC patients correlated with high HCC stage and poor overall
      survival and disease-free survival. In vitro and in vivo, recombinant human IL
      37b inhibited proliferation and metastasis in HCC cells. Furthermore, IL-37b
      inhibited epithelial mesenchymal transition in HCC cells in vitro by
      downregulating IL-6, pSTAT3 (Y705), N-cadherin, and vimentin expression and by
      upregulating E-cadherin expression. These effects were partially reversed by
      transfection of adenovirus encoding human IL-6. CONCLUSIONS: IL-37b inhibits HCC
      growth, metastasis and epithelial mesenchymal transition by regulating IL-6/STAT3
      signaling. Serum IL-37b may be a biomarker for HBV-HCC and its staging.

PMID- 30201412
TI  - Evaluation of DNA extraction methods to detect bacterial targets in aerosol
      samples.
AB  - DNA-based monitoring of pathogens in aerosol samples requires extraction methods
      that provide high recovery of DNA. To identify a suitable method, we evaluated
      six DNA extraction methods for recovery of target-specific DNA from samples with
      four bacterial agents at low abundance (<10,000 genome copies per detection
      assay). These methods differed in rigor of cell disruption, approach for DNA
      capture, and extent of DNA purification. The six methods varied 1000-fold in the
      recovery of DNA from spores or cells of surrogates of Bacillus anthracis,
      Yersinia pestis, Burkholderia pseudomallei, and Francisella tularensis, each at
      about 105 CFU per sample. A custom method using paramagnetic Dynabeads for DNA
      capture greatly outperformed the other five methods. The cDynabead method
      provided about 80% recovery of target-specific DNA. The cDynabead method and a
      filtration method were further evaluated for DNA recovery from bacterial agents
      spiked on filters (c.a. 105 CFU of each agent per filter quadrant) that were
      subsequently used to collect background outdoor air particulates for 24-h. The
      filtration method generally failed to recover detectable quantities of target DNA
      from the spiked filters, suggesting at least a 100-fold loss of target DNA during
      extraction, whereas the custom cDynabead method consistently yielded DNA
      sufficient for target detection.

PMID- 30201413
TI  - There is no additional bactericidal efficacy of Environmental Protection Agency
      registered disinfectant towelettes after surface drying or beyond label contact
      time.
AB  - BACKGROUND: Disinfectant towelettes are commonly used for surface disinfection to
      prevent health care-associated infections; however, there is limited consensus as
      to whether a surface needs to remain wet for the full label contact time after
      the disinfectant towelette has been used in order for complete efficacy to be
      achieved. The purpose of this study was to quantify the effect of contact time,
      including times before and after a product dries, on bactericidal efficacy of 6
      towelette products registered by the Environmental Protection Agency . METHODS:
      Six disinfectant towelette products were tested at varying contact times,
      including defined label contact times. Quantitative Environmental Protection
      Agency MB-33-00 was used to measure disinfectant efficacy against Staphylococcus
      aureus on Formica. Complete dry time for each disinfectant was measured
      gravimetrically. RESULTS: There were significant differences in dry times among
      the towelette products; contact time did not have a significant effect on
      bactericidal efficacy. There was no longitudinal effect when a disinfectant's
      contact time was greater than defined label contact time, irrespective of whether
      the product was wet or dry on the surface. DISCUSSION: Overall, bactericidal
      efficacy varied by towelette product tested and surface area wiped. Wiping larger
      surface areas may lead to decreased bactericidal efficacy but is product
      dependent. CONCLUSIONS: There was no additional bactericidal effect after a
      product dried, indicating that extended contact times beyond when the product
      dries will not enhance disinfection.

PMID- 30201414
TI  - Using the agile implementation model to reduce central line-associated
      bloodstream infections.
AB  - BACKGROUND: Central line-associated bloodstream infections (CLABSIs) are among
      the most common hospital-acquired infections and can lead to increased patient
      morbidity and mortality rates. Implementation of practice guidelines and
      recommended prevention bundles has historically been suboptimal, suggesting that
      improvements in implementation methods could further reductions in CLABSI rates.
      In this article, we describe the agile implementation methodology and present
      details of how it was successfully used to reduce CLABSI. METHODS: We conducted
      an observational study of patients with central line catheters at 2 adult
      tertiary care hospitals in Indianapolis from January 2015 to June 2017. RESULTS:
      The intervention successfully reduced the CLABSI rate from 1.76 infections per
      1,000 central line days to 1.24 (rate ratio = 0.70; P = .011). We also observed
      reductions in the rates of Clostridium difficile and surgical site infections,
      whereas catheter-associated urinary tract infections remained stable.
      CONCLUSIONS: Using the AI model, we were able to successfully implement evidence
      based practices to reduce the rate of CLABSIs at our facility.

PMID- 30201415
TI  - Bacterial contamination of saline nasal irrigations in children: An original
      research.
AB  - Microbiologic analysis of nasal saline irrigations (NSIs) used in hospitalized
      children was performed. Of 253 collected samples, 24.9% were positive, and the
      number of positive samples significantly increased over time (P < .001).
      Staphylococcus aureus was the most frequently detected bacterium (28.6%). None of
      the 118 patients who received NSIs developed a nasosinusal infection.
      Colonization by cutaneous and environmental germs is frequent and develops early.
      Hygienic measures should be advocated to reduce contamination.

PMID- 30201416
TI  - Family support and media considerations with conjoined twins.
AB  - Conjoined twins offer unique challenges for the family and medical care team
      including psychosocial stressors, religious dilemmas and public relation
      considerations. The involvement of social workers, child life specialists,
      chaplains and public relation experts is an important component in the care of
      conjoined twins. In this paper, we discuss the issues that could be encountered
      when supporting families with conjoined twins and strategies to address them.

PMID- 30201417
TI  - Stage distribution utilizing magnetic resonance imaging in an unselected
      population of primary rectal cancers.
AB  - BACKGROUND: Pre-operative radiotherapy (RT) or chemo-radiotherapy (CRT) are
      sometimes recommended prior to rectal cancer surgery, but guideline
      recommendations vary. The aim was to describe stage distribution and other
      important characteristics required for the treatment decision of patients with
      primary rectal cancers utilizing magnetic resonance imaging (MRI) in an
      unselected population. PATIENTS AND METHODS: All 796 histopathologically verified
      rectal adenocarcinomas diagnosed 2010-2015 in two counties in Sweden (population
      630,000 in 2015) were identified. Staging with pelvic MRI unless
      contraindications were present, treatment and pathology followed Swedish
      guidelines. RESULTS: Twenty-three % of cases (n = 186) had distant metastases at
      diagnosis, demonstrating more advanced tumor and nodal stages when compared with
      non-metastatic patients (p < 0.001), and they more often displayed MRI-identified
      mucinous features and extramural vascular invasion (EMVI) than non-metastatic
      tumors (p < 0.001 for both). In non-metastatic patients, 8% displayed clinical
      stage T1 (cT1), 21% cT2, and 53% cT3; one-third of the latter threatened or
      involved the mesorectal fascia (MRF+). Almost 20% had stage cT4 (4% cT4a, 14%
      cT4b) of which 50% were considered "non-resectable". EMVI was seen in 33% of
      cT3M0 tumors and in 48% of cT4M0 tumors. CONCLUSIONS: In an unselected
      population, approximately 80% of primary rectal cancers are referred to as
      "locally advanced" (stage II-III, or cT3-4 or N+), meaning that they, according
      to many international guidelines, are recommended neo-adjuvant treatment. This
      study provides a detailed description of the clinical stages and presence of
      characteristics identifiable on MRI which are of importance when assessing the
      needs for RT/CRT, when using different guidelines.

PMID- 30201418
TI  - Better preoperative physical performance reduces the odds of complication
      severity and discharge to care facility after abdominal cancer resection in
      people over the age of 70 - A prospective cohort study.
AB  - INTRODUCTION: Reduced functional reserve in older people, combined with the
      surgical stress, may increase the likelihood of adverse postoperative outcomes.
      The objective of this study was to examine the associations between preoperative
      physical performance and severity of postoperative complications, length of stay
      (LoS), and discharge destination in older people after abdominal cancer surgery.
      METHODS: Between December 2015 and December 2017, a prospective cohort study
      examined 197 individuals >= 70 years of age awaiting abdominal cancer surgery.
      Measures of physical performance (walking distance, functional leg strength, grip
      strength, inspiratory muscle strength, gait speed) and self-reported physical
      activity were conducted preoperatively, and postoperative outcomes were collected
      within 30 days of surgery. RESULTS: Fifty-four percent experienced at least one
      postoperative complication at 30-day follow-up, including 10% with severe
      complications. In the multivariable analysis, better walking distance, functional
      leg strength, grip strength, inspiratory muscle strength, and gait speed were
      associated with reduced odds of higher complication severity. Better preoperative
      inspiratory muscle strength was associated with shorter LoS in hospital, and
      better preoperative physical activity level, walking distance, grip strength, and
      maximal walking speed reduced the odds of being postoperatively discharged to
      further care rather than to home. CONCLUSION: The results emphasize the
      importance of acknowledging the physical fitness of the older individual rather
      than chronological age. Objectively measured physical performance is an important
      addition to conventional risk assessments in preoperative care. This will help to
      identify patients at high risk and in need of an alternative preoperative
      pathway, which might include personalized preoperative exercise.

PMID- 30201420
TI  - Task-switching abilities in pre-manifest Huntington's disease subjects.
AB  - INTRODUCTION: Huntington's Disease (HD) cognitive dysfunction occurs before
      unequivocal motor signs become apparent. The predominant early cognitive abnormal
      domains may include deficits in psychomotor speed, negative emotion recognition
      and executive functioning. Our study is aimed to investigate the executive
      control of cognition in pre-manifest (pre) HD subjects, by means of a task
      switching protocol. METHODS: We recruited 30 pre-HD subjects and 18 age-, sex-
      and education-matched Healthy Controls (HC). Subjects were assigned to two
      experimental groups: 15 pre-HD1 with a Total Motor Score (TMS) <=4 (far from
      onset) and 15 pre-HD2 with a 5 <= TMS<=9 (near to onset and Diagnostic Confidence
      Level (DCL) still<4). Two different tasks were performed in rapid and random
      succession, so that the task was either changed from one trial to the next one
      (switch trials) or repeated (repetition trials). Switch trials are usually slower
      than repetitions, causing a so-called Switch Cost (SC). RESULTS: Pre-HD subjects
      had worse performance than HC in the switch and repetition trials, as indicated
      by increased SC and reaction times. In particular, pre-HD2 showed impaired
      switching abilities with reaction times slower than pre-HD1 and HC. CONCLUSIONS:
      Our study highlighted a task-switching impairment since HD was still at a pre
      manifest stage. Such abnormalities worsen when pre-HD subjects start to show
      subtle motor manifestations, still nonspecific and insufficient to define the
      clinical diagnosis of HD (DCL<4). Considering that such abilities have obvious
      implications for activities of daily living, early cognitive rehabilitation
      programs addressing such deficits might be useful in the premanifest stage of the
      disease.

PMID- 30201422
TI  - Alpha-synuclein and the prion hypothesis in Parkinson's disease.
AB  - Protein intracellular inclusions within the central nervous system are hallmarks
      of several progressive neurodegenerative disorders in man. The protein
      constituents of those deposits and the affected regions within the brain differ
      from one neurodegenerative disorder to another. Until recently, the vicious
      circle consisting of spread, seeded assembly and accumulation over time within
      the central nervous system of misfolded proteins aggregates was thought to be
      restricted to the prion protein PrP. Recent reports suggest that other protein
      aggregates spread and amplify within the central nervous system leading to
      distinct diseases. How alpha-synuclein protein assemblies traffic between cells,
      amplify by recruiting endogenous monomeric alpha-synuclein and cause distinct
      synucleinopathies is unclear. I review here the experimental evidence supporting
      the propagation of alpha-synuclein mega-dalton assemblies in a manner similar to
      prion protein aggregates. I also describe how alpha-synuclein aggregates. I also
      explain why the aggregation of alpha-synuclein may lead to distinct
      synucleinopathies.

PMID- 30201419
TI  - Management of resectable esophageal and gastric (mixed adeno)neuroendocrine
      carcinoma: A nationwide cohort study.
AB  - INTRODUCTION: The aim of this study is to provide insight in accuracy of
      diagnosing, current treatment and survival in patients with resectable esophageal
      and gastric neuroendocrine- and mixed adenoneuroendocrine carcinomas (NEC,
      MANEC). METHODS: All patients with esophageal or gastric (MA)NEC, who underwent
      surgical resection between 2006 and 2016, were identified from the Dutch national
      registry for histo- and cytopathology (PALGA). Patients with a neuroendocrine
      tumor lower than grade 3 were excluded. Data on patients, treatment and outcomes
      were retrieved from the patient records. Diagnosis by endoscopic biopsy was
      compared with diagnosis by resection specimen. Kaplan Meier survival analysis was
      performed. RESULTS: A total of 49 patients were identified in 25 hospitals,
      including 21 patients with esophageal (MA)NEC and 26 patients with gastric
      (MA)NEC on resection specimen. Biopsy diagnosis of (MA)NEC was correct in 23/27
      patients. However, 20/47 patients with definitive diagnosis of (MA)NEC, were
      misdiagnosed on biopsy. Neoadjuvant therapy was administered in 13 (62%)
      esophageal (MA)NECs and 12 (46%) gastric (MA)NECs. Survival curves were similar
      with and without neoadjuvant therapy. One (4.8%) esophageal (MA)NEC and 4 (15%)
      gastric (MA)NECs died within 90 days postoperatively. For esophageal (MA)NEC the
      median overall survival (OS) after surgery was 37 months and 1-, 3- and 5-year OS
      were 71%, 50% and 35%, respectively. For gastric (MA)NEC, the median OS was 23
      months and 1-, 3- and 5-year OS were 62%, 50% and 39%, respectively. CONCLUSION:
      Localized esophageal and gastric (MA)NEC are often misdiagnosed on endoscopic
      biopsies. After resection, long-term survival was achieved in respectively 35%
      and 39% of patients.

PMID- 30201421
TI  - Severity dependent distribution of impairments in PSP and CBS: Interactive
      visualizations.
AB  - BACKGROUND: Progressive supranuclear palsy (PSP) -Richardson's Syndrome and
      Corticobasal Syndrome (CBS) are the two classic clinical syndromes associated
      with underlying four repeat (4R) tau pathology. The PSP Rating Scale is a
      commonly used assessment in PSP clinical trials; there is an increasing interest
      in designing combined 4R tauopathy clinical trials involving both CBS and PSP.
      OBJECTIVES: To determine contributions of each domain of the PSP Rating Scale to
      overall severity and characterize the probable sequence of clinical progression
      of PSP as compared to CBS. METHODS: Multicenter clinical trial and natural
      history study data were analyzed from 545 patients with PSP and 49 with CBS.
      Proportional odds models were applied to model normalized cross-sectional PSP
      Rating Scale, estimating the probability that a patient would experience
      impairment in each domain using the PSP Rating Scale total score as the index of
      overall disease severity. RESULTS: The earliest symptom domain to demonstrate
      impairment in PSP patients was most likely to be Ocular Motor, followed jointly
      by Gait/Midline and Daily Activities, then Limb Motor and Mentation, and finally
      Bulbar. For CBS, Limb Motor manifested first and ocular showed less probability
      of impairment throughout the disease spectrum. An online tool to visualize
      predicted disease progression was developed to predict relative disability on
      each subscale per overall disease severity. CONCLUSION: The PSP Rating Scale
      captures disease severity in both PSP and CBS. Modelling how domains change in
      relation to one other at varying disease severities may facilitate detection of
      therapeutic effects in future clinical trials.

PMID- 30201423
TI  - Movement disorders in autoimmune encephalitis and paraneoplastic neurological
      syndromes.
AB  - Movement disorders are extremely common and diverse in autoimmune encephalitis
      (AE) and paraneoplastic neurological syndromes (PNS). They can sometimes
      represent the main neurological disorder of a given patient, or just be part of a
      larger neurological syndrome. Early diagnosis of AE or PNS is essential, as the
      associated abnormal movements can be effectively treated with immunomodulators.
      Nevertheless, the diagnosis is often delayed because of the large number of
      differential diagnoses (infections, metabolic disorders, genetic and degenerative
      diseases) and because the semiology of abnormal movements arising during AE and
      PNS is often not well known. However, there are highly specific clinical
      features, depending on the associated autoantibodies, age and gender of the
      patient, and associated cancers. Such features are likely to rely on specific
      mechanisms, the knowledge of which could lead to new therapeutic proposals. Also,
      the growing body of work on AE and PNS provides a better understanding of the
      links between immunity and neuronal degeneration, and immunity and genetic
      specificities. Thus, the purpose of this article is to present the current
      knowledge and different subtypes of movement disorders associated with AE and
      PNS, as well as the mechanisms that can lead to neuronal dysfunction.

PMID- 30201424
TI  - Correction.

PMID- 30201426
TI  - Evidence of body size and shape stasis driven by selection in Patagonian lizards
      of the Phymaturus patagonicus clade (Squamata: Liolaemini).
AB  - During the speciation process sibling lineages accumulate differences in time
      (e.g. genetic, morphological, and/or ecological). Phenotypic traits such as size
      or shape, however, could experience rapid changes or show stasis depending on
      their role in survival and reproduction. The clade Phymaturus patagonicus
      includes 26 species characterized by a conservative morphology, and all inhabit
      rock crevice microhabitats in arid environments. In this study we quantify levels
      of morphological divergence (size and shape) among the multiple species relative
      to interspecific molecular divergence, and show that most species have not
      diverged significantly in size and/or shape to permit unambiguous species
      diagnosis with morphological data alone. The influence of stabilizing selection
      for an adaptive optimum in body size and head shape was detected for 13 of the 16
      variables analyzed in an Ornstein-Uhlenbeck model. The strict dependence of these
      species to rock-crevice microenvironments likely explains the observed
      morphological stasis across the many species of the Phymaturus patagonicus group.

PMID- 30201427
TI  - A simple strategy for recovering ultraconserved elements, exons, and introns from
      low coverage shotgun sequencing of museum specimens: Placement of the partridge
      genus Tropicoperdix within the galliformes.
AB  - Next-generation DNA sequencing (NGS) offers a promising way to obtain massive
      numbers of orthologous loci to understand phylogenetic relationships among
      organisms. Of particular interest are old museum specimens and other samples with
      degraded DNA, where traditional sequencing methods have proven to be challenging.
      Low coverage shotgun sequencing and sequence capture are two widely used NGS
      approaches for degraded DNA. Sequence capture can yield sequence data for large
      numbers of orthologous loci, but it can only be used to sequence genomic regions
      near conserved sequences that can be used as probes. Low coverage shotgun
      sequencing has the potential to yield different data types throughout the genome.
      However, many studies using this method have often generated mitochondrial
      sequences, and few nuclear sequences, suggesting orthologous nuclear sequences
      are likely harder to recover. To determine the phylogenetic position of the
      galliform genus Tropicoperdix, whose phylogenetic position is currently
      uncertain, we explored two strategies to maximize data extraction from low
      coverage shotgun sequencing from approximately 100-year-old museum specimens from
      two species of Tropicoperdix. One approach, a simple read mapping strategy,
      outperformed the other (a reduced complexity assembly approach), and allowed us
      to obtain a large number of ultraconserved element (UCE) loci, relatively
      conserved exons, more variable introns, as well as mitochondrial genomes.
      Additionally, we demonstrated some simple approaches to explore possible
      artifacts that may result from the use of degraded DNA. Our data placed
      Tropicoperdix within a clade that includes many taxa characterized with
      ornamental eyespots (peafowl, argus pheasants, and peacock pheasants), and
      established relationships among species within the genus. Therefore, our study
      demonstrated that low coverage shotgun sequencing can easily be leveraged to
      yield substantial amounts and varying types of data, which opens the door for
      many research questions that might require information from different data types
      from museum specimens.

PMID- 30201425
TI  - Simultaneous Passive Acoustic Mapping and Magnetic Resonance Thermometry for
      Monitoring of Cavitation-Enhanced Tumor Ablation in Rabbits Using Focused
      Ultrasound and Phase-Shift Nanoemulsions.
AB  - Thermal ablation of solid tumors via focused ultrasound (FUS) is a non-invasive
      image-guided alternative to conventional surgical resection. However, the
      usefulness of the technique is limited in vascularized organs because of
      convection of heat, resulting in long sonication times and unpredictable thermal
      lesion formation. Acoustic cavitation has been found to enhance heating but
      requires use of exogenous nuclei and sufficient acoustic monitoring. In this
      study, we employed phase-shift nanoemulsions (PSNEs) to promote cavitation and
      incorporated passive acoustic mapping (PAM) alongside conventional magnetic
      resonance imaging (MRI) thermometry within the bore of a clinical MRI scanner.
      Simultaneous PAM and MRI thermometry were performed in an in vivo rabbit tumor
      model, with and without PSNE to promote cavitation. Vaporization and cavitation
      of the nanoemulsion could be detected using PAM, which led to accelerated
      heating, monitored with MRI thermometry. The maximum heating assessed from MRI
      was well correlated with the integrated acoustic emissions, illustrating
      cavitation-enhanced heating. Examination of tissue revealed thermal lesions that
      were larger in the presence of PSNE, in agreement with the thermometry data.
      Using fixed exposure conditions over 94 sonications in multiple animals revealed
      an increase in the mean amplitude of acoustic emissions and resulting temperature
      rise, but with significant variability between sonications, further illustrating
      the need for real-time monitoring. The results indicate the utility of combined
      PAM and MRI for monitoring of tumor ablation and provide further evidence for the
      ability of PSNEs to promote cavitation-enhanced lesioning.

PMID- 30201428
TI  - Keep the momentum going: pushing the boundaries of clinical learning and
      assessment.

PMID- 30201429
TI  - Critically appraised paper: The addition of exercise training to a weight-loss
      program improves clinical control in adults with asthma [commentary].

PMID- 30201430
TI  - [ENT benign lesions and pseudo-tumors: Case No. 5].

PMID- 30201431
TI  - Hyaluronic acid-capped compact silica-supported mesoporous titania nanoparticles
      for ligand-directed delivery of doxorubicin.
AB  - Mesoporous titania nanoparticles (MTN), owing to their high surface area to
      volume ratio and tunable pore sizes, appear capable of delivering sizable amounts
      of drug payloads, and hence, show considerable promise as drug delivery
      candidates in cancer therapy. We designed silica-supported MTN (MTNst) coated
      with hyaluronic acid (HA) to effectively deliver doxorubicin (DOX) for breast
      cancer therapy. The HA coating served a dual purpose of stabilizing the payload
      in the carriers as well as actively targeting the nanodevices to CD44 receptors.
      The so-formed HA-coated MTNst carrying DOX (HA/DOX-MTNst) had spheroid particles
      with a considerable drug-loading capacity and showed significantly superior in
      vitro cytotoxicity against MDA-MB-231 cells as compared to free DOX. HA/DOX-MTNst
      markedly improved the cellular uptake of DOX in an apparently CD44 receptor
      dependent manner, and increased the number of apoptotic cells as compared to free
      DOX. These nanoplatforms accumulated in large quantities in the tumors of MDA-MB
      231 xenograft tumor-bearing mice, where they significantly enhanced the
      inhibition of tumor growth compared to that observed with free DOX with no signs
      of acute toxicity. Based on these excellent results, we deduced that HA/DOX-MTNst
      could be successfully used for targeted breast cancer therapy. STATEMENT OF
      SIGNIFICANCE: This is the first study to use silica-supported mesoporous titania
      nanoparticles (MTNst) for doxorubicin (DOX) delivery to treat breast cancer,
      which exhibited effective and enhanced in vitro and in vivo apoptosis and tumor
      growth inhibition. Solid silica was used to support the mesoporous TiO2 resulting
      in MTNst, which efficiently incorporated a high DOX payload. The hyaluronic acid
      (HA) coating over the MTNst surface served a dual purpose of first, stabilizing
      DOX inside the MTNst (capping agent), and second, directing the nanoplatform
      device to CD44 receptors that are highly expressed in MDA-MB-231 cells (targeting
      ligand). The NPs exhibited highly efficacious in vitro tumor-cell killing and
      excellent in vivo tumor regression, highlighting the enormous promise of this
      system for breast cancer therapy.

PMID- 30201432
TI  - Metallic microneedles with interconnected porosity: A scalable platform for
      biosensing and drug delivery.
AB  - Metallic-based microneedles (MNs) offer a robust platform for minimally invasive
      drug delivery and biosensing applications due to their mechanical strength and
      proven tissue and drug compatibility. However, current designs suffer from
      limited functional surface area or challenges in manufacturing scalability. Here,
      porous 316L stainless steel MN patches are proposed. Fabricated through a
      scalable manufacturing process, they are suitable for storage and delivery of
      drugs and rapid absorption of fluids for biosensing. Fabrication of these MNs
      involves hot embossing a patch of stainless steel-based feedstock, sintering at
      1100  degrees C and subsequent electropolishing. Optimisation of this
      manufacturing process yields devices that maintain mechanical integrity yet
      possess high surface area and associated porosity (36%) to maximise loading
      capacity. Similarly, a small pore size has been targeted (average diameter 2.22
      MUm, with 90% between 1.56 MUm and 2.93 MUm) to maximise capillarity and loading
      efficiency. This porous network has a theoretical wicking rate of 4.7 MUl/s and
      can wick-up 27 +/- 5 MUl of fluid through capillary action which allows for
      absorption of pharmaceuticals for delivery. When inserted into a metabolite
      loaded skin model, the MNs absorbed and recovered 17 +/- 3 MUl of the metabolite
      solution. The drug delivery performance of the porous metallic MNs (22.4 +/- 4.9
      ug/cm2) was found to be threefold higher than that of topical administration (7.1
      +/- 4.3 ug/cm2). The porous metallic MN patches have been shown to insert into
      porcine skin under a 19 N load. These results indicate the potential of design
      for-manufacturing porous stainless steel MNs in biosensing and drug delivery
      applications. STATEMENT OF SIGNIFICANCE: Microneedles are micro-scale sharp
      protrusions used to bypass the stratum corneum, the skin's outer protective
      layer, and painlessly access dermal layers suitable for drug delivery and
      biosensing. Despite a depth of research in the area we have not yet seen large
      scale clinical adoption of microneedle devices. Here we describe a device
      designed to address the potential barriers to adoption seen by other microneedles
      devices. We have developed a scalable, cost effective process to produce medical
      grade stainless steel microneedle patches which passively absorb and store drugs
      or interstitial fluid though a porous network and capillary action. This device,
      with low manufacturing and regulatory burdens may help the large-scale adoption
      of microneedles.

PMID- 30201433
TI  - Electroneutral polymersomes for combined cancer chemotherapy.
AB  - Combination cancer chemotherapy provides an important treatment tool, both as an
      adjuvant and neoadjuvant treatment, this shift in focus from mono to combination
      therapies has led to increased interest in drug delivery systems (DDS). DDSs,
      such as polymersomes, are capable of encapsulating large amounts of multiple
      drugs with both hydrophilic and hydrophobic properties simultaneously, as well as
      offering a mechanism to combat multi drug resistant cancers and poor patient
      tolerance of the cytotoxic compounds utilised. In this article, we report the
      formulation and evaluation of a novel electroneutral polymersome capable of high
      encapsulation efficacies for multiple drugs (Doxorubicin, 5-Fluorouracil and
      leucovorin). The in-vivo biodistribution of the polymersome were established and
      they were found to accumulate largely in tumour tissue. Polymersome encapsulating
      the three chemotherapeutic drugs were assessed both in-vitro (BxPC-3 cell line)
      and in-vivo (following intratumoral and intravenous administration) and compared
      with the same concentration of the three drugs in solution. We report better
      efficacy and higher maximum tolerated dose for our combination drug loaded
      polymersomes in all experiments. Furthermore, intratumorally injected combination
      drug loaded polymersomes exhibited a 62% reduction in tumour volume after 13 days
      when compared with the free combination solutions. A smaller differential of 13%
      was observed for when treatment was administered intravenously however,
      importantly less cardiotoxicity was displayed from the polymersomal DDS. In this
      study, expression of a number of survival-relevant genes in tumours treated with
      the free chemotherapy combination was compared with expression of those genes in
      tumours treated with the polymersomes harbouring those drugs and the significance
      of findings is discussed. STATEMENT OF SIGNIFICANCE: The shift in focus from mono
      to combination chemotherapies has led to an increased interest in the role of
      drug delivery systems (DDS). Liposomes, although commercialized for mono therapy,
      have lower loading capacities and stability than their polymeric counterpart,
      polymersomes. Polymersomes are growing in prevalence as their advantageous
      properties are better understood and exploited. Here we present a novel
      polymersome for the encapsulation of three anticancer compounds. This is the
      first time this particular polymersome has been used to encapsulate these three
      compounds with both an in-vitro and in-vivo evaluation carried out. This work
      will be of interest to those in the field of combination therapy, drug delivery,
      drug toxicity, multidrug resistance, liposomes, DDS and polymersomes.

PMID- 30201434
TI  - pLoc_bal-mGneg: Predict subcellular localization of Gram-negative bacterial
      proteins by quasi-balancing training dataset and general PseAAC.
AB  - One of the hottest topics in molecular cell biology is to determine the
      subcellular localization of proteins from various different organisms. This is
      because it is crucially important for both basic research and drug development.
      Recently, a predictor called "pLoc-mGneg" was developed for identifying the
      subcellular localization of Gram-negative bacterial proteins. Its performance is
      overwhelmingly better than that of the other predictors for the same purpose,
      particularly in dealing with multi-label systems in which some proteins, called
      "multiplex proteins", may simultaneously occur in two or more subcellular
      locations. Although it is indeed a very powerful predictor, more efforts are
      definitely needed to further improve it. This is because pLoc-mGneg was trained
      by an extremely skewed dataset in which some subset (subcellular location) was
      about 5 to 70 times the size of the other subsets. Accordingly, it cannot avoid
      the biased consequence caused by such an uneven training dataset. To alleviate
      such a consequence, we have developed a new and bias-reducing predictor called
      pLoc_bal-mGneg by quasi-balancing the training dataset. Cross-validation tests on
      exactly the same experiment-confirmed dataset have indicated that the proposed
      new predictor is remarkably superior to pLoc-mGneg, the existing state-of-the-art
      predictor in identifying the subcellular localization of Gram-negative bacterial
      proteins. To maximize the convenience for most experimental scientists, a user
      friendly web-server for the new predictor has been established at http://www.jci
      bioinfo.cn/pLoc_bal-mGneg/, by which users can easily get their desired results
      without the need to go through the detailed mathematics.

PMID- 30201435
TI  - Imaging Features of the Whole Uterus Volume CT Perfusion and Influence Factors of
      Blood Supply: A Primary Study in Patients with Cervical Squamous Carcinoma.
AB  - RATIONALE AND OBJECTIVES: To explore the imaging features of whole uterus volume
      CT perfusion (vCTP) and the influence factors of blood supply in cervical
      squamous carcinoma (CSC). MATERIALS AND METHODS: vCTP was performed on a 640
      slice computed tomography system in 43 patients with CSC diagnosed by biopsy, and
      24 cases of them underwent magnetic resonance imaging. The size of the tumor was
      measured on vCTP and magnetic resonance (MR) images. Perfusion parameters,
      including arterial blood flow (AF), blood volume, and permeability surface (PS),
      were measured by two radiologists, using interclass correlation coefficient to
      evaluate the interobserver reliability. The difference of tumor size and
      perfusion data was analyzed by paired t test and rank sum test. The correlation
      of perfusion parameters with some factors was analyzed by Pearson or Spearman
      correlation analysis. RESULTS: Tumor sizes were not significantly different
      between vCTP and MR images. The interclass correlation coefficient of each
      parameter was 0.818-0.945. The AF value of CSC was significantly higher than
      normal uterine body, and the blood volume and PS values of CSC were not
      statistically different compared with those of normal uterine body. There was no
      significant difference in AF value of CSC among different FIGO stages and
      pathological grades. The AF and PS values of CSC were negatively correlated with
      the age of the patients. CONCLUSION: The vCTP could accurately shows the size of
      the CSC with use of MR as the reference standard, and its perfusion parameters
      have good measurement stability; the CSC was hypervascular, but this trend was
      less pronounced in older women.

PMID- 30201436
TI  - MicroRNA-183 and microRNA-96 are associated with autoimmune responses by
      regulating T cell activation.
AB  - MircoRNAs (miRs) are small molecules that regulate gene expression at the
      posttranscriptional level. They have been proposed to be involved in the
      regulation of several immune responses including autoimmunity. Here, we
      identified miR-183 and miR-96 to be highly expressed in CD4+ T cells from
      peripheral blood of Graves' orbitopathy (GO) patients as well as in human and
      murine T cells upon activation in vitro. By using Luciferase-based binding
      assays, we identified EGR-1 as target for miR-183 and miR-96. Overexpression of
      miR-183 and miR-96 in murine CD4+ T cells by retroviral gene transfer resulted in
      decreased EGR-1 and PTEN expression, elevated Akt phosphorylation and enhanced
      proliferation. In contrast, treatment of murine CD4+ T cells with specific
      antagomiRs increased EGR-1 and PTEN expression and interfered with the
      proliferative activity upon stimulation in vitro. Strikingly, adoptive transfer
      of miR-183 and miR-96 overexpressing antigen-specific T cells into INS-HA/Rag2KO
      mice accelerated the development of autoimmune diabetes, whereas transfer of
      antagomiR-treated cells delayed the disease onset. These results indicate that
      miR-183 and miR-96 have the ability to regulate the strength of T cell activation
      and thereby the development and severity of T cell-dependent autoimmune diseases.

PMID- 30201437
TI  - A perspective on SOAL, a stochastic model of neuronal outgrowth.
AB  - A functional nervous system requires neuronal connections to be made in a highly
      detailed and stereotypic manner. During development, neurons extend processes
      that can branch, travel in different directions, and form elaborate patterns.
      These patterns are essential for forming proper connections. Patterns of
      outgrowth are produced by complex molecular events that cause a fluid membrane to
      move. The collective impact of dynamic fluctuating events at the microscale cause
      the patterns of outgrowth observed at the macroscale. Patterning is genetically
      controlled, but the effects genes have on membrane movement and patterning are
      not well understood. To better understand how genes control outgrowth patterns, I
      propose a statistically-oriented asymmetric localization (SOAL) model. This model
      is based on the theory that receptor-mediated outgrowth activity is
      stochastically oriented and when the system is at equilibrium there is an equal
      probability of outgrowth being oriented in any direction. This concept allows a
      statistical mechanics approach that can correlate the microscale events of
      outgrowth to the observed macroscale patterns. Proof-of-concept experiments
      suggest this approach can be used to study the effect genes have on outgrowth
      patterns. The SOAL model also provides a new theoretical framework for
      conceptualizing guidance. According to the model, outgrowth activity becomes
      asymmetrically localized to the neuron's surface in a statistically dependent
      manner. Extracellular cues regulate the probability of outgrowth along the
      surface and the orientation of outgrowth fluctuates across the surface over time.
      This creates a directional bias that allows the growth cone to navigate in
      reference to the composition of extracellular cues.

PMID- 30201438
TI  - Patterns of progression after 68Ga-PSMA-ligand PET/CT-guided radiotherapy for
      recurrent prostate cancer.
AB  - We demonstrated in 108 patients with increased prostate-specific antigen levels,
      who received 68Ga-PSMA-ligand PET/CT-guided radiotherapy (RT) for recurrent
      oligometastatic disease after primary therapy for prostate cancer (PCa) that PSMA
      ligand PET/CT-guided RT for relapsed PCa with limited tumor burden allowed
      individualized treatment approaches, provided effective local control and
      considerably prolonged biochemical progression-free survival. The PSMA-ligand
      PET/CT patterns of progression revealed a shift in the pattern of metastases
      towards skeletal involvement and distant lymph node metastases.

PMID- 30201439
TI  - The radiotherapy-sensitization effect of cantharidin: Mechanisms involving cell
      cycle regulation, enhanced DNA damage, and inhibited DNA damage repair.
AB  - BACKGROUND: Cantharidin is an inhibitor of protein phosphatase 2 A (PP2A), and
      has been frequently used in clinical practice. In our previous study, we proved
      that cantharidin could arrest cell cycle in G2/M phase. Since cells at G2/M phase
      are sensitive to radiotherapy, in the present study, we investigated the
      radiotherapy-sesitization effect of cantharidin and the potential mechanisms
      involved. METHODS: Cell growth was determined by MTT assay. Cell cycle was
      evaluated by flow cytometry. DNA damage was visualized by phospho-Histone H2A.X
      staining. Expression of mRNA was tested by microarray assay and real-time PCR.
      Clinical information and RNA-Seq expression data were derived from The Cancer
      Genome Atlas (TCGA) pancreatic cancer cohort. Survival analysis was obtained by
      Kaplan-Meier estimates. RESULTS: Cantharidin strengthened the growth inhibition
      effect of irradiation. Cantharidin drove pancreatic cancer cells out of quiescent
      G0/G1 phase and arrested cell cycle in G2/M phase. As a result, cantharidin
      strengthened DNA damage which was induced by irradiation. Moreover, cantharidin
      repressed expressions of several genes participating in DNA damage repair,
      including UBE2T, RPA1, GTF2HH5, LIG1, POLD3, RMI2, XRCC1, PRKDC, FANC1, FAAP100,
      RAD50, RAD51D, RAD51B and DMC1, through JNK, ERK, PKC, p38 and/or NF-kappaB
      pathway dependent manners. Among these genes, worse overall survival for
      pancreatic cancer patients were associated with high mRNA expressions of POLD3,
      RMI2, PRKDC, FANC1, RAD50 and RAD51B, all of which could be down-regulated by
      cantharidin. CONCLUSION: Cantharidin can sensitize pancreatic cancer cells to
      radiotherapy. Multiple mechanisms, including cell cycle regulation, enhanced DNA
      damage, and inhibited DNA damage repair, may be involved.

PMID- 30201440
TI  - Different biological behaviors in left-sided pancreatic cancer according to
      Yonsei criteria: Proposal of a modified Yonsei criteria score.
AB  - BACKGROUND/OBJECTIVES: Our institutional experience has demonstrated that
      bloodless and margin-negative resection is the most potent prognostic factor in
      treating left-sided pancreatic cancer and we developed selection guideline. The
      Yonsei criteria (YC) is selection criteria for oncologically safe and effective
      resection of left-sided pancreatic cancer by a minimally invasive approach. In
      this study, we investigated whether left-sided pancreatic cancer with YC can be
      more individualized to predict long-term survival by using clinically and
      pathologically detectable parameters. METHODS: From January 2000 to December
      2015, 105 patients underwent distal pancreatectomy for left-sided pancreatic
      cancer. The medical records of the patients were retrospectively reviewed.
      RESULTS: Among clinically and pathologically detectable parameters to predict
      tumor conditions, radiologically determined tumor size (p = 0.080) and SUVmax (p
      = 0.086) were identified as predictors of early tumor recurrence with marginal
      significance. Among them, 20% of the patients with YC were identified as having
      the most favoring tumor condition, with an modified YC score of 3. The patient
      group with the lowest mYC score was found to have a very long disease-free
      survival time, with a mean of 108 months, which was statistically different from
      those with other mYC scores (mYC score = 4, mean 47.1 months [95% CI: 27.8-69.5]
      vs. mYC score = 5, mean 36.7 months [95% CI: 12.7-60.7], vs. mYC score = 6, mean
      10.7 months [95% CI: 3.9-17.4]). CONCLUSIONS: Modified Yonsei criteria score can
      predict long-term survival in resected left-sided pancreatic cancer. And patients
      within YC with a mYC score = 3 could have a favorable survival outcome.

PMID- 30201441
TI  - Editorial overview: Synthetic biomolecules.

PMID- 30201442
TI  - Sugar and ice: Immunoelectron microscopy using cryosections according to the
      Tokuyasu method.
AB  - Since the pioneering work of Kiyoteru Tokuyasu in the 70ths the use of thawed
      cryosections prepared according to the "Tokuyasu-method" for immunoelectron
      microscopy did not lose popularity. We owe this method a whole subcellular world
      described by discrete gold particles pointing at cargo, receptors and organelle
      markers on delicate images of the inner life of a cell. Here we explain the
      procedure of sample preparation, sectioning and immunolabeling in view of recent
      developments and the reasoning behind protocols including some historical
      perspective. Cryosections are prepared from chemically fixed and sucrose
      infiltrated samples and labeled with affinity probes and electron dense markers.
      These sections are ideal substrates for immunolabeling, since antigens are not
      exposed to organic solvent dehydration or masked by resin. Instead, the
      structures remain fully hydrated throughout the labeling procedure. Furthermore,
      target molecules inside dense intercellular structural elements, cells and
      organelles are accessible to antibodies from the section surface. For the
      validation of antibody specificity several approaches are recommended including
      knock-out tissue and reagent controls. Correlative light and electron microscopy
      strategies involving correlative probes are possible as well as correlation of
      live imaging with the underlying ultrastructure. By applying stereology, gold
      labeling can be quantified and evaluated for specificity.

PMID- 30201443
TI  - Intestinal and non-intestinal nasal cavity adenocarcinoma: Impact of wood dust
      exposure.
AB  - : The aim of the present study was to investigate the role of wood dust exposure
      in intestinal (ITAC) and non-intestinal type (non-ITAC) nasal adenocarcinoma, so
      as to improve understanding of the oncogenic mechanisms in the light of the
      recent literature and of evo-devo concepts. MATERIALS AND METHODS: All
      consecutive patients operated in our institution for nasal adenocarcinoma
      diagnosed on anatomopathology between May 2004 and February 2014 were included.
      Surgical specimens were examined twice by independent pathologists, blind to wood
      dust exposure status. Clinical and demographic data, including wood dust
      exposure, were collected for the two groups (ITAC and non-IATC). RESULTS: 90
      patients (84 ITAC, 6 non-ITAC) were included. No non-ITAC patients had history of
      wood dust exposure, versus 83/84 cases (99%) in ITAC (mean exposure duration:
      30+/-16 years; range 2-65 years). Only 12 ITAC patients (18%) were still exposed
      at diagnosis. ITAC may develop long after the end of wood dust exposure (up to 60
      years). Eight patients (12%) had exposure durations of less than 5 years. Latency
      between onset of exposure and onset of disease did not decrease with exposure
      duration. CONCLUSION: Exposure to wood dust, even for short periods of time,
      incurs a risk of developing ITAC, usually after a long latency period. Any
      exposure requires lifetime follow-up, to ensure prompt treatment. Factors leading
      to the development of nasal ITAC and non-ITAC are probably different. The analogy
      with Barret's esophagus and esophageal adenocarcinoma may shed light on the
      oncogenesis of nasal ITAC.

PMID- 30201445
TI  - Effects of childhood adversity and resilience on Taiwanese youth health
      behaviors.
AB  - BACKGROUND: Adverse childhood experiences (ACEs) can leave negative impacts on
      one's health behaviors or social functioning later in life. Resilient
      characteristics have been shown to mitigate effects against risk behaviors in
      developing adolescents. However, clinical and research attention has rarely been
      given to jointly consider the effects of ACEs and resilient characteristics on
      health behaviors in Taiwanese youth. METHOD: A total of 200 individuals aged 15
      22 years were recruited from primary care settings, communities, and schools.
      Participants completed questionnaires assessing their ACEs, resilient
      characteristics, and health behaviors. Univariate analysis was firstly used to
      describe the correlates of ACEs and resilient characteristics. Further
      multivariate logistic regression analysis was used to examine the association of
      both factors with health behaviors. RESULTS: More than half (61.5%) of those
      surveyed had been exposed to at least one category of ACE. Verbal (37%) and
      physical (21%) abuses were the most common types of ACEs. The counts in the ACE
      categories were associated with being involved in physical fights (odds ratio
      1.28 [confidence interval 1.01-1.63]), property damage (1.29 [1.03-1.61]),
      running away from home (1.30 [1.05-1.60]), bullying victimization (1.37 [1.16
      1.61]), and sleep problems/tiredness (1.25 [1.03-1.52]). Meanwhile, resilience
      scores were associated with decreased odds of infrequent seatbelt use (0.47 [0.23
      0.97]), low fruit and vegetable intake (0.42 [0.21-0.86]) unsatisfied body image
      (0.46 [0.22-0.97]), and sleep problems/tiredness (0.37 [0.18-0.79]). CONCLUSIONS:
      ACEs and resilience characteristics play a significant role in shaping youth
      health behaviors. Further research should be undertaken to identify ways to build
      resilience against health risks in youth with prior ACE exposure.

PMID- 30201446
TI  - Investigation of the effect of training attachment behaviors to pregnant mothers
      on some physical indicators of their infants from birth to three months based on
      the separation of male and female infants.
AB  - BACKGROUND: Maternal attachment to the fetus during pregnancy improves infant's
      growth and development and is an important criterion for public health. The aim
      is to investigate the effect of training attachment behaviors to pregnant women
      on some growth health indicators of infants. METHODS: This is a clinical trial
      with convenience sampling which was conducted on 190 pregnant women in Hafez
      Hospital in Shiraz who randomly classified into intervention and control groups.
      For the intervention group, 6 sessions of 90-min classes were held. After
      delivery, both groups were compared in terms of physical growth (weight, height,
      head circumference) at birth, one and three months after birth. The data were
      analyzed using repeated Measurement. RESULTS: Weight increase in female infants
      in the intervention group compared to the control group was significant at birth
      (p = 0.016), one month (p = 0.010) and three months after birth (p = 0.014).
      Height increase in female infants in the intervention group compared to the
      control group was significant at birth (p = 0.025), one month (p < 0.001) and
      three months after birth (p = 0.009). Male gender was not statistically
      significant in any age group but it increased the size of the head circumference
      of three-month-old infants. CONCLUSION: Training of attachment skills to mothers
      improves height and weight of female infants in three steps. The average index
      for boys in the intervention group was higher than that of control group, but it
      was not significant.

PMID- 30201444
TI  - A single-dose plasmid-launched live-attenuated Zika vaccine induces protective
      immunity.
AB  - BACKGROUND: Vaccines are the most effective means to fight and eradicate
      infectious diseases. Live-attenuated vaccines (LAV) usually have the advantages
      of single dose, rapid onset of immunity, and durable protection. DNA vaccines
      have the advantages of chemical stability, ease of production, and no cold chain
      requirement. The ability to combine the strengths of LAV and DNA vaccines may
      transform future vaccine development by eliminating cold chain and cell culture
      with the potential for adventitious agents. METHODS: A DNA-launched LAV was
      developed for ZIKV virus (ZIKV), a pathogen that recently caused a global public
      health emergency. The cDNA copy of a ZIKV LAV genome was engineered into a DNA
      plasmid. The DNA-LAV plasmid was delivered into mice using a clinically proven
      device TriGridTM to launch the replication of LAV. FINDINGS: A single-dose
      immunization as low as 0.5 MUg of DNA-LAV plasmid conferred 100% seroconversion
      in A129 mice. All seroconverted mice developed sterilizing immunity, as indicated
      by no detectable infectious viruses and no increase of neutralizing antibody
      titers after ZIKV challenge. The immunization also elicited robust T cell
      responses. In pregnant mice, the DNA-LAV vaccination fully protected against ZIKV
      induced disease and maternal-to-fetal transmission. High levels of neutralizing
      activities were detected in fetal serum, indicating maternal-to-fetal humoral
      transfer. In male mice, a single-dose vaccination completely prevented testis
      infection, injury, and oligospermia. INTERPRETATION: The remarkable simplicity
      and potency of ZIKV DNA-LAV warrant further development of this vaccine
      candidate. The DNA-LAV approach may serve as a universal vaccine platform for
      other plus-sense RNA viruses. FUND: National Institute of Health, Kleberg
      Foundation, Centers for Disease Control and Prevention, University of Texas
      Medical Branch.

PMID- 30201447
TI  - Efficacy of MontanideTM ISA 763 A VG as aquatic adjuvant administrated with an
      inactivated Vibrio harveyi vaccine in turbot (Scophthalmus maximus L.).
AB  - Turbot (Scophthalmus maximus L.) is a commercially important fish species in
      China. Despite of its great economic potential, fish farms often suffer severe
      economic losses due to certain fish diseases. Vaccination has become a common
      strategy to prevent diseases caused by pathogens in aquaculture industry.
      However, no inactivated vaccine against Vibrio harveyi of turbot has been
      reported so far. In this study, we developed an inactivated vaccine using
      formalin-killed cells of V. harveyi and the efficacy of a commercial adjuvant
      MontanideTM ISA 763 A VG on the inactivated vaccine was evaluated. We found that
      with an optimum vaccine dosage at 1.0 * 108 CFU/fish, a high relative percent
      survival (RPS) more than 75% was observed at 4 weeks post vaccination (w.p.v.).
      Moreover, enhanced antibody titer, lysozyme activity, total serum protein and
      antibacterial property in sera of vaccinated fish were observed at 4, 8, 12 and
      16 w.p.v. In conclusion, we developed an efficient inactivated vaccine against V.
      harveyi in turbot, which not only induced humoral immunity, but also enhanced
      initial innate immune response for long-term protection.

PMID- 30201448
TI  - Histopathological analysis and the immune related gene expression profiles of
      mandarin fish (Siniperca chuatsi) infected with Aeromonas hydrophila.
AB  - Hemorrhagic septicemia of mandarin fish (Siniperca chuatsi) was mainly caused by
      Aeromonas hydrophila which was an opportunistic pathogen. In recent years, the
      disease has caused tremendous economic loss with high morbidity and mass
      mortality in the mandarin fish breeding industry. Histopathological analysis and
      the immune related gene expression profiles of mandarin fish (S. chuatsi)
      infected with A. hydrophila were investigated in this study. Transmission
      electron microscopy (TEM) images showed that the cells of A. hydrophila densely
      covered with a mass of fimbriae. Histopathological analysis revealed that
      inflammation, vacuolization and extensive necrosis existed in the gill, liver,
      spleen and head kidney of the diseased fish. Quantitative real-time PCR was
      performed to measure mRNA expression levels for six immune related genes in
      mandarin fish after A. hydrophila infection. The transcriptional analysis of
      these immune related genes demonstrated that the expression levels of major
      histocompatibility complex class II (MHC II), T cell receptor alpha (TCRalpha),
      tumor necrosis factor alpha (TNFalpha), CC chemokine 3, interleukin 8 (IL-8) and
      Hepcidin were strongly up-regulated in spleen and head kidney of mandarin fish
      post-infection. These results will contribute to further study on the
      pathogenesis and host defensive system in A. hydrophila infection.

PMID- 30201449
TI  - Past 50 years, present, and future of the Korean Nutrition Society.
AB  - Created in 1967, the Korean Nutrition Society (KNS) has been a vital contributor
      to the development of the health and nutrition of South Korea. With members from
      many different fields focusing on nutrition and health sciences, the impact of
      the KNS has not only been felt in South Korea, but also worldwide. The KNS has
      helped to establish and maintain dietary recommendations in addition to providing
      ways to make nutrition information readily available to members, as well as the
      public. The KNS has also established professional journals to advance scientific
      discoveries in nutrition and health. With 50 years of progress from the KNS,
      their contributions to nutrition and health will continue to have an impact
      throughout the world. To celebrate the 50th anniversary and growth of the KNS, an
      International Conference entitled "Integrative Nutrition for an Active Life" was
      held by the KNS in November 2017. The articles in this special issue of Nutrition
      Research are to commemorate the KNS efforts.

PMID- 30201450
TI  - Relationship between antioxidant defense in Acanthamoeba spp. infected lungs and
      host immunological status.
AB  - The role of oxidative stress in the pathogenicity of acanthamoebiasis is an
      important aspect of the intricate and complex host-parasite relationship. The aim
      of this experimental study was to determine oxidative stress through the
      assessment of lipid peroxidation product (LPO) levels and antioxidant defense
      mechanism in Acanthamoeba spp. lung infections in immunocompetent and
      immunosuppressed hosts. In Acanthamoeba spp. infected immunocompetent mice we
      noted a significant increase in lung lipid peroxidation products (LPO) at 8 days
      and 16 days post infection (dpi). There was a significant upregulation in lung
      LPO in immunocompetent and immunosuppressed mice infected by Acanthamoeba spp. at
      16 dpi. The superoxide dismutase activity decreased significantly in lungs in
      immunosuppressed mice at 8 dpi. The catalase activity was significantly
      upregulated in lungs in immunocompetent vs. immunosuppressed group and in
      immunocompetent vs. control mice at 16 dpi. The glutathione reductase activity
      was significantly lower in immunosuppressed group vs. immunosuppressed control at
      24 dpi. We found significant glutathione peroxidase downregulation in
      immunocompetent and immunosuppressed groups vs. controls at 8 dpi, and in
      immunosuppressed vs. immunosuppressed control at 16 dpi. The consequence of the
      inflammatory response in immunocompetent and immunosuppressed hosts in the course
      of experimental Acanthamoeba spp. infection was the reduction of the antioxidant
      capacity of the lungs resulting from changes in the activity of antioxidant
      enzymes. Therefore, the imbalance between oxidant and antioxidant processes may
      play a major role in pathology associated with Acanthamoeba pneumonia.

PMID- 30201451
TI  - Evidence of transplacental transmission of Encephalitozoon cuniculi genotype II
      in murine model.
AB  - Microsporidia are obligate intracellurar unicellular parasite of wide range of
      vertebrates. Although ingestion or inhalation of microsporidian spores is the
      main route of infection, assumed vertical transmission was described in some
      mammals. The present study was focused on proof of vertical transmission in mice
      under experimental conditions. Mice were infected with E. cuniculi genotype II
      intraperitoneally after mating, or perorally followed by mating in acute or
      chronic phase of infection. Fetuses were delivered by Caesarean section or mice
      were kept up to the parturition. Some of cubs were immediately after birth
      transferred to uninfected surrogate mothers. Group of cubs was immunosuppressed.
      All cubs were examined using polymerase chain reaction for the presence of
      Encephalitozoon after birth or in their age of 3 or 6 weeks, respectively. All
      fetuses delivered by Caesarean section, which were intraperitoneally or perorally
      infected were negative as well as all neonatal mice and youngsters tested in age
      of 6 weeks. Only immunosuppressed cubs and cubs of immunodeficient mice in age of
      21 days were positive for Encephalitozoon cuniculi genotype II. Present results
      provided the evidence that transplacental transmission of Encephalitozoon
      cuniculi in mice occurs, but the mechanism of these transport is still unknown.

PMID- 30201452
TI  - Baicalein represses TGF-beta1-induced fibroblast differentiation through the
      inhibition of miR-21.
AB  - Fibroblast-to-myofibroblast differentiation is a highly important pathological
      characteristic of pulmonary fibrosis. In this study, we aimed to investigate the
      effects and mechanisms of baicalein on the differentiation of human lung
      fibroblasts. Baicalein reduced the levels of alpha-smooth muscle actin (alpha
      SMA) mRNA and protein expression in TGF-beta1-treated human lung fibroblasts. It
      also decreased the contents of collagen type I and fibronectin in time- and dose
      dependent manners, and retarded TGF-beta1-stimulated alpha-SMA filament
      formation. Baicalein diminished the expression of miR-21, and miR-21 mimics
      partially antagonized the effects of baicalein. Additionally, Baicalein inhibited
      the miR-21 transcriptor STAT3 activity but not AP-1 activity. Moreover, the
      expression of Spry 1 protein, a miR-21 known target, was improved by baicalein
      treatment, but the level of Smurf2 protein, another miR-21 target, was not
      interfered. Collectively, these results demonstrated that baicalein can attenuate
      TGF-beta1-induced human lung fibroblast differentiation by inhibiting the miR-21
      expression.

PMID- 30201453
TI  - A novel FPCL model producing directional contraction through induction of
      fibroblast alignment by biphasic pulse direct current electric field.
AB  - Although parallel alignment of fibroblasts to the tension lines of scar has been
      evidenced in vivo, how scar contracture generates directional contraction remains
      largely unclear due to the lack of effective in vitro model. Fibroblast populated
      collagen lattice (FPCL), a widely used in vitro model, fails to mimic scar
      contracture since it produces concentric contraction with the random orientation
      of fibroblast. We hypothesized that a novel FPCL model with fibroblast alignment
      might produce directional contraction and then simulate scar contracture better.
      Here, we showed that although direct current electric fields (DCEFs) enabled
      fibroblasts aligned perpendicularly to the field vector, it also promoted
      electrotactic migration of fibroblast in FPCL. By contrast, biphasic pulse direct
      current electric fields (BPDCEFs), featured by reversal of the EF direction
      periodically, abolished the electrotactic migration, but induced fibroblast
      alignment in a pulse frequency dependent manner. Specifically, BPDCEF at a pulse
      frequency of 0.0002 Hz induced fibroblast alignment comparable to that induced by
      DCEF under the same field strength (300 mV/mm), leading to an enhanced
      contraction of FPCL along the direction of cell alignment. FPCL pretreated by
      BPDCEF showed an elliptical contraction whereas it was concentric in control
      FPCL. Further study revealed that F-actin redistributions acted as a key
      mechanism for the induction of fibroblasts alignment by BPDCEF. Cytochalasin D,
      an inhibitor of actin dynamics, abolished F-actins redistribution, and
      significantly suppressed the fibroblasts alignment and the directional
      contraction of FPCL. Importantly, BPDCEF significantly increased RhoA activity in
      fibroblasts, while this response was attenuated by C3 transferase pre-treatment,
      a potent inhibitor of RhoA, caused F-actin depolymerization and actin filament
      bundle randomly distributed. Taken together, our study suggests a crucial role
      for fibroblast orientation in scar contracture, and provides a novel FPCL model
      that may be feasible and effective for investigating scar contracture in vitro.

PMID- 30201454
TI  - Epigenetics-by-sex interaction for somatization conferred by methylation at the
      promoter region of SLC6A4 gene.
AB  - BACKGROUND: Depression, anxiety and somatoform disorders are all more prevalent
      in women than in men. However, specific biological mechanisms contributing to
      such sex differences remain unknown. Serotonergic pathways are involved in mood
      and behavior regulation and thus have been suggested to be altered in several
      psychiatric disorders. The serotonin transporter (SERT), encoded by SLC6A4 gene,
      has received major attention due to its crucial role in serotonergic
      transmission. METHODS: 148 monozygotic twin subjects were assessed for (i)
      lifetime categorical diagnosis of anxious-depressive disorders, following SCID-I
      based DSM-IV criteria, and (ii) current psychiatric symptomatology, from a
      dimensional approach, by means of the Brief Symptom Inventory (BSI). SLC6A4 gene
      methylation was analyzed by means of Infinium HumanMethylation450 in a subset of
      the sample. CpG-specific methylation at the promoter region of SLC6A4 gene was
      further analyzed by means of pyrosequencing technology in the total sample.
      RESULTS: SLC6A4 methylation was found to be significantly higher in women when
      compared to men independent of DSM-IV diagnosis. SLC6A4 methylation was further
      associated with the BSI-derived somatization dimension. CONCLUSIONS: Female
      hypermethylation of a discrete region located within SLC6A4 promoter region could
      underlie differential SERT expression in women when compared to men and could be
      one of the causative mechanisms by which women exhibit increased prevalence of
      somatic symptoms.

PMID- 30201455
TI  - Real-World Outcomes of Acute Ischemic Stroke Treatment with Intravenous
      Thrombolysis: A Systematic Review and Meta-Analysis.
AB  - BACKGROUND: Evidence from outside the typical clinical research setting, such as
      the real-world setting, complements evidence coming from randomized controlled
      trials. The purpose of this study was to evaluate all available evidence from the
      real-world observational trials about long-term outcomes of treatment with
      intravenous (IV) recombinant tissue-type plasminogen activator (rt-PA) compared
      with not treated with IV rt-PA (non-rt-PA) in patients with acute ischemic
      stroke. METHODS: We searched PubMed and Embase until March 1, 2018 for
      observational studies reporting matched or adjusted results comparing IV rt-PA
      versus non-rt-PA in patients with acute ischemic stroke. Outcomes assessed
      included all-cause mortality, hospital readmission rates, and independence rates.
      Hazard ratios with 95% confidence intervals were used as a measure of comparing
      between patients treated with IV rt-PA and non-rt-PA. RESULTS: Six observational
      trials with 16,399 participants were identified. The use of IV rt-PA in acute
      ischemic stroke patients was associated with a lower risk of mortality (hazard
      ratio .61; 95% confidence interval, .52-.70; P < .00001), and there was no
      heterogeneity across trials. There was no evidence of an effect on hospital
      readmission rates and independence rates. CONCLUSIONS: IV rt-PA is associated
      with reduced long-term mortality in acute ischemic stroke patients.

PMID- 30201456
TI  - Upper Limb Ischemic Postconditioning as Adjunct Therapy in Acute Stroke Patients:
      A Randomized Pilot.
AB  - OBJECTIVE: This study aims to observe the clinical effect of upper limb ischemic
      postconditioning (LIPostC) as an adjunct to treatment with acute stroke patients,
      possibly due to increased cerebral perfusion. METHODS: We perform a randomized
      blinded placebo controlled trial in nonthrombolysis patients with acute ischemic
      stroke, within 72hours of ictus, divided into the LIPostC group and control
      group. The LIPostC group is induced by 4 cycles of intermittent repeated limb
      ischemia: alternating 5 minutes inflation (20mm Hg above systolic blood pressure)
      and 5 minutes deflation performed manually using a standard upper arm blood
      pressure cuff in the nonparetic arm. The control group receives a sham procedure
      (cuff inflation to 30mm Hg). Patients underwent the intervention from the time of
      enrollment to Day 14. Comparison of National Institutes of Health Stroke Scale
      (NIHSS) score, cerebral infarction volume, relative Perfusion weighted imaging
      (PWI) parameters (regional relative cerebral blood flow, regional relative mean
      transit time; preintervention [day 0], day 14, day 90), modified Rankin Scale
      (mRS; the preintervention score [day 0], the curative ratio at day 90 [we define
      0-1 score as close to recovery or full recovery]). RESULTS: Sixty eligible
      patients with acute stroke (29 LIPostC and 31 control) are recruited age 65years
      (SD 12.22), blood pressure 156/74mm Hg (SD 14/10), and NIHSS score 5.98 (SD
      3.35), mRS score 2.25 (SD .79). Only 1 in the LIPostC group is intolerant the
      first cycle to give up. All patients tolerate the sham procedure. Two patients
      experience recurrent stroke versus none in the LIPostC group. Day 90, compared
      with the control group, there is a significant decrease the NIHSS score, regional
      relative mean transit time (P < .05) and increase the curative ratio of mRS,
      regional relative cerebral blood flow(P < .05) in the LIPostC group, which
      infarct volume decreased by 31.3% (P < .05). CONCLUSIONS: LIPostC after acute
      stroke is well tolerated and appears safe and feasible. LIPostC may improve
      neurological outcome, and protective mechanisms may be increased cerebral blood
      flow to improve cerebral perfusion. A larger trial is warranted.

PMID- 30201457
TI  - Screening for Fabry Disease in Japanese Patients with Young-Onset Stroke by
      Measuring alpha-Galactosidase A and Globotriaosylsphingosine.
AB  - BACKGROUND: Fabry disease is an X-linked lysosomal storage disorder caused by
      mutations in GLA, which encodes the enzyme alpha-galactosidase A (alpha-Gal A).
      Although the prevalence of Fabry disease in patients with stroke has been
      reported to range from 0% to 4%, few cohort studies have examined Japanese stroke
      patients. We aimed to clarify the prevalence of Fabry disease and the frequency
      of GLA mutations among patients with young-onset stroke in Japan. METHODS: From
      April 2015 to December 2016, we enrolled patients with young-onset (<=60 years
      old) ischemic stroke or intracerebral hemorrhage. We measured alpha-Gal A
      activity and the concentration of globotriaosylsphingosine in plasma. Genetic
      evaluations were performed in patients with low alpha-Gal A activity or high
      concentrations of globotriaosylsphingosine. RESULTS: Overall, 516 patients
      (median age of onset, 52 years old; 120 women) were consecutively enrolled in
      this study. Five patients (4 men and 1 woman) had low alpha-Gal A activity, and
      no patients were detected with the screen for plasma globotriaosylsphingosine
      levels. The genetic analysis did not identify a causative mutation responsible
      for classic Fabry disease in any of the patients, but 2 patients (.4%) carried
      the p.E66Q in GLA. CONCLUSIONS: No patient with Fabry disease was detected in our
      young-onset stroke cohort.

PMID- 30201458
TI  - Improving the Accuracy of Scores to Predict Gastrostomy after Intracerebral
      Hemorrhage with Machine Learning.
AB  - BACKGROUND: Gastrostomy placement after intracerebral hemorrhage indicates the
      need for continued medical care and predicts patient dependence. Our objective
      was to determine the optimal machine learning technique to predict gastrostomy.
      METHODS: We included 531 patients in a derivation cohort and 189 patients from
      another institution for testing. We derived and tested predictions of the
      likelihood of gastrostomy placement with logistic regression using the GRAVo
      score (composed of Glasgow Coma Scale <=12, age >50 years, black race, and
      hematoma volume >30 mL), compared to other machine learning techniques (kth
      nearest neighbor, support vector machines, random forests, extreme gradient
      boosting, gradient boosting machine, stacking). Receiver Operating Curves (Area
      Under the Curve, [AUC]) between logistic regression (the technique used in GRAVo
      score development) and other machine learning techniques were compared. Another
      institution provided an external test data set. RESULTS: In the external test
      data set, logistic regression using the GRAVo score components predicted
      gastrostomy (P < 0.001), however, with a lower AUC (0.66) than kth nearest
      neighbors (AUC 0.73), random forests (AUC 0.74), Gradient boosting machine (AUC
      0.77), extreme gradient boosting (AUC 0.77), (P < 0.01 for all compared to
      logistic regression). Results from the internal test set were similar.
      CONCLUSIONS: Machine learning techniques other than logistic regression (eg,
      random forests, extreme gradient boost, and kth nearest neighbors) were
      significantly more accurate for predicting gastrostomy using the same independent
      variables. Machine learning techniques may assist clinicians in identifying
      patients likely to need interventions.

PMID- 30201459
TI  - Efficacy and Safety of Citalopram for the Treatment of Poststroke Depression: A
      Meta-Analysis.
AB  - OBJECTIVE: To objectively evaluate the efficacy and safety of citalopram versus
      other antidepressant drugs in poststroke depression (PSD) treatment. METHODS: We
      searched randomized controlled trials (RCTs) that compared citalopram with other
      Selective serotonin reuptake inhibitors (SSRIs) and Serotonin norepinephrine
      reuptake inhibitor (SNRIs) on PSD treatment. The methodological quality of RCTs
      was assessed according to the Cochrane risk of bias tool. Meta-analysis was
      conducted using RevMan 5.3 software with standard mean difference (SMD) or
      Relative risk (RR) and their 95% confidence interval (CI). RESULTS: A total of 20
      studies involving 1485 patients were included .The RR of efficacy index compared
      to other SSRIs was 1.04 [95% CI: .98-1.09, P = .17], and to SNRIs was 1.01 [95%
      CI: .93-1.09, P = .83]. The RR of cure index compared to other SSRIs was .99 [95%
      CI: .82-1.19, P = .88], and to SNRIs was .95 [95% CI: .71-1.27, P = .74].
      Significant decreases on Hamilton Depression Scale scores were observed in favor
      of citalopram when compared to other SSRIs after 4-, 6-week treatment [SMD = 
      .44, 95% CI: -.85 to -.03, P = .03; SMD = -.50, 95% CI: -.98 to -.02, P = .04],
      and no significant difference was found with SNRIs in any week [P > .05]. The
      rate of adverse effects also showed no significant difference between citalopram
      and other antidepressants [P > .05]. CONCLUSIONS: This meta-analysis indicates
      that the efficacy of citalopram is similar to that of other SSRIs and SNRIs, but
      citalopram takes action faster than other SSRIs. The adverse effects of
      citalopram have no significant difference compared to other antidepressants and
      those adverse effects are less and mild.

PMID- 30201460
TI  - Reduction of Ischemia Reperfusion-Related Brain Hemorrhage by Stachybotrys
      Microspora Triprenyl Phenol-7 in Mice With Antioxidant Effects.
AB  - BACKGROUND: Stachybotrys microspora triprenyl phenol-7 (SMTP-7) has both
      thrombolytic and anti-inflammatory effects, but its neuroprotective effects on
      cerebral ischemia are still unclear. The present study assessed the antioxidative
      and neurovascular unit (NVU) protective effects of SMTP-7 using transient middle
      cerebral artery occlusion (tMCAO) mice. METHODS: After 60 minutes tMCAO, 0.9%
      NaCl, tissue-type plasminogen activator (tPA), SMTP-7 or tPA + SMTP-7 was
      intravenously administrated through subclavian vein just before the reperfusion,
      and these mice were examined at 24 hours after reperfusion. We histologically
      assessed the hemorrhage and expressive changes of antioxidative markers in
      brains. RESULTS: SMTP-7 treatment showed a similar antithrombotic effect to tPA,
      but significantly decreased the hemorrhage volumes and the number of 4-HNE, 3-NT
      and 8-OHdG positive cells, meanwhile, ameliorated the decrease of collagen IV in
      the ischemic brains. However, tPA + SMTP-7 treatment did not decrease hemorrhage
      volumes nor showed NVU protective effect. CONCLUSIONS: The present study
      suggested that SMTP-7 provided therapeutic benefits for ischemic stroke through
      antioxidative and NVU protective effects unlike tPA alone or tPA + SMTP-7.

PMID- 30201461
TI  - Impaired brain glymphatic flow in experimental hepatic encephalopathy.
AB  - BACKGROUND AND AIMS: Neuronal function is exquisitely sensitive to alterations in
      extracellular environment. In patients with hepatic encephalopathy (HE),
      accumulation of metabolic waste products and noxious substances in the
      interstitial fluid of the brain is thought to be a consequence of the liver
      disease and may contribute to neuronal dysfunction and cognitive impairment. This
      study was designed to test the hypothesis that the accumulation of these
      substances, such as bile acids, may result from reduced clearance from the brain.
      METHODS: In a rat model of chronic liver disease with minimal HE (the bile duct
      ligation (BDL) model), we used emerging dynamic contrast-enhanced MRI and mass
      spectroscopy techniques to assess the efficacy of the glymphatic system, which
      facilitates clearance of solutes from the brain. Immunofluorescence of aquaporin
      4 (AQP4) and behavioural experiments were also performed. RESULTS: We identified
      discrete brain regions (olfactory bulb, prefrontal cortex and hippocampus) of
      altered glymphatic clearance in BDL rats, which aligned with
      cognitive/behavioural deficits. A significantly lower level of AQP4 expression
      was observed compared to the vasculature marker in both the olfactory bulb and
      prefrontal cortex in HE, which could be a contributing factor to the
      pathophysiological mechanisms underlying the impairment in glymphatic function
      observed in BDL rats. CONCLUSIONS: This study provides the first experimental
      evidence of impaired glymphatic flow in HE, potentially mediated by decreased
      AQP4 expression in the affected regions. LAY SUMMARY: The 'glymphatic system' is
      a newly discovered brain-wide pathway that facilitates clearance of various
      substances that accumulate in the brain due to its activity. This study evaluated
      whether the function of this system is altered in a model of brain dysfunction
      that occurs in cirrhosis. For the first time, we identified that the clearance of
      substances from the brain in cirrhosis is reduced because this clearance system
      is defective. This study proposes a new mechanism of brain dysfunction in
      patients with cirrhosis and provides new targets for therapy.

PMID- 30201463
TI  - Functional MRS with J-edited lactate in human motor cortex at 4 T.
AB  - While functional MRI (fMRI) localizes regions of brain activation, functional MRS
      (fMRS) provides insights into metabolic underpinnings. Previous fMRS studies
      detected task-induced lactate increase using short echo-time non-edited 1H-MRS
      protocols, where lactate changes depended on accurate exclusion of overlapping
      lactate and lipid/macromolecule signals. Because long echo-time J-difference 1H
      MRS detection of lactate is less susceptible to this shortcoming, we posited if J
      edited fMRS protocol could reliably detect metabolic changes in the human motor
      cortex during a finger-tapping paradigm in relation to a reliable measure of
      basal lactate. Our J-edited fMRS protocol at 4T was guided by an fMRI pre-scan to
      determine the 1H-MRS voxel placement in the motor cortex. Because lactate and
      beta-hydroxybutyrate (BHB) follow similar J-evolution profiles we observed both
      metabolites in all spectra, but only lactate showed reproducible task-induced
      modulation by 0.07 mM from a basal value of 0.82 mM. These J-edited fMRS results
      demonstrate good sensitivity and specificity for task-induced lactate modulation,
      suggesting that J-edited fMRS studies can be used to investigate the metabolic
      underpinning of human cognition by measuring lactate dynamics associated with
      activation and deactivation fMRI paradigms across brain regions at magnetic field
      lower than 7T.

PMID- 30201464
TI  - Inhibitory and excitatory mechanisms in the human cingulate-cortex support
      reinforcement learning: A functional Proton Magnetic Resonance Spectroscopy
      study.
AB  - The dorsal anterior cingulate cortex (dACC) is crucial for motivation, reward-
      and error-guided decision-making, yet its excitatory and inhibitory mechanisms
      remain poorly explored in humans. In particular, the balance between excitation
      and inhibition (E/I), demonstrated to play a role in animal studies, is difficult
      to measure in behaving humans. Here, we used functional magnetic-resonance
      spectroscopy (1H-fMRS) to measure the brain's major inhibitory (GABA) and
      excitatory (Glutamate) neurotransmitters during reinforcement learning with three
      different conditions: high cognitive load (uncertainty); probabilistic
      discrimination learning; and a control null-condition. Participants learned to
      prefer the gain option in the discrimination phase and had no preference in the
      other conditions. We found increased GABA levels during the uncertainty
      condition, potentially reflecting recruitment of inhibitory systems during high
      cognitive load when trying to learn. Further, higher GABA levels during the null
      (baseline) condition correlated with improved discrimination learning. Finally,
      glutamate and GABA levels were correlated during high cognitive load. These
      results suggest that availability of dACC inhibitory resources enables successful
      learning. Our approach helps elucidate the potential contribution of the balance
      between excitation and inhibition to learning and motivation in behaving humans.

PMID- 30201462
TI  - The effects of breastfeeding versus formula-feeding on cerebral cortex maturation
      in infant rhesus macaques.
AB  - Breastfeeding is positively associated with several outcomes reflecting early
      brain development and cognitive functioning. Brain neuroimaging studies have
      shown that exclusively breastfed children have increased white matter and
      subcortical gray matter volume compared to formula-fed children. However, it is
      difficult to disentangle the effects of nutrition in breast milk from other
      confounding factors that affect brain development, particularly in studies of
      human subjects. Among the nutrients provided by human breast milk are the
      carotenoid lutein and the natural form of tocopherol, both of which are
      selectively deposited in brain. Lutein is the predominant carotenoid in breast
      milk but not in most infant formulas, whereas infant formulas are supplemented
      with the synthetic form of tocopherol. In this study, a non-human primate model
      was used to investigate the effects of breastfeeding versus formula-feeding, as
      well as lutein and natural RRR-alpha-tocopherol supplementation of infant
      formula, on brain maturation under controlled experimental conditions. Infant
      rhesus macaques (Macaca mulatta) were exclusively breastfed, or were fed infant
      formulas with different levels and sources of lutein and alpha-tocopherol. Of
      note, the breastfed group were mother-reared whereas the formula-fed infants were
      nursery-reared. Brain structural and diffusion MR images were collected, and
      brain T2 was measured, at two, four and six months of age. The mother-reared
      breastfed group was observed to differ from the formula-fed groups by possessing
      higher diffusion fractional anisotropy (FA) in the corpus callosum, and lower FA
      in the cerebral cortex at four and six months of age. Cortical regions exhibiting
      the largest differences include primary motor, premotor, lateral prefrontal, and
      inferior temporal cortices. No differences were found between the formula groups.
      Although this study did not identify a nutritional component of breast milk that
      could be provided to infant formula to facilitate brain maturation consistent
      with that observed in breastfed animals, our findings indicate that breastfeeding
      promoted maturation of the corpus callosum and cerebral cortical gray matter in
      the absence of several confounding factors that affect studies in human infants.
      However, differences in rearing experience remain as a potential contributor to
      brain structural differences between breastfed and formula fed infants.

PMID- 30201466
TI  - Empowerment of the nurses role in patients treated with clozapine.

PMID- 30201465
TI  - Error-related modulations of the sensorimotor post-movement and foreperiod beta
      band activities arise from distinct neural substrates and do not reflect efferent
      signal processing.
AB  - While beta activity has been extensively studied in relation to voluntary
      movement, its role in sensorimotor adaptation remains largely uncertain.
      Recently, it has been shown that the post-movement beta rebound as well as beta
      activity during movement-preparation are modulated by movement errors. However,
      there are critical functional differences between pre- and post-movement beta
      activities. Here, we addressed two related open questions. Do the pre- and post
      movement error-related modulations arise from distinct neural substrates? Do
      these modulations relate to efferent signals shaping muscle-activation patterns
      or do they reflect integration of sensory information, intervening upstream of
      the motor output? For this purpose, first we exploited independent component
      analysis (ICA) which revealed a double dissociation suggesting that distinct
      neural substrates are recruited in error-related beta-power modulations observed
      before and after movement. Second, we compared error-related beta oscillation
      responses observed in two bimanual reaching tasks involving similar movements but
      different interlimb coordination, and in which the same mechanical perturbations
      induced different behavioral adaptive responses. While the task difference was
      not reflected in the post-movement beta rebound, the pre-movement beta activity
      was differently modulated according to the interlimb coordination. Critically, we
      show an uncoupling between the behavioral and the electrophysiological responses
      during the movement preparation phase, which demonstrates that the error-related
      modulation of the foreperiod beta activity does not reflect changes in the motor
      output from primary motor cortex. It seems instead to relate to higher level
      processing of sensory afferents, essential for sensorimotor adaptation.

PMID- 30201467
TI  - Is advanced nursing practice possible without a nurse prescribing?

PMID- 30201468
TI  - Development of advanced practice nursing (APN): the international context.

PMID- 30201469
TI  - Shared decision making for the allergist.
AB  - OBJECTIVE: Shared decision making (SDM) is becoming more commonly appreciated and
      used in medical practice as a way to empower patients who are facing treatment
      preference-sensitive conditions, such as allergic rhinitis, atopic dermatitis,
      food allergy, and persistent asthma. The purpose of this review is to educate the
      allergy health care provider about how SDM works and provide practical advice and
      allergist-specific SDM resources. DATA SOURCES: PubMed and online patient
      decision aid resources. STUDY SELECTIONS: Studies and reviews relevant to SDM and
      patient decision aids relevant to the allergy health care provider were selected
      for discussion. RESULTS: There are ethical, practical, economic, and
      psychological imperatives for the implementation of quality SDM, particularly for
      chronic diseases. Many benefits and barriers of SDM have been identified and
      models have been developed to encourage implementation of quality SDM. For the
      allergy health care provider, SDM for asthma has been shown to improve adherence,
      outcomes, and patient satisfaction with care. Patient decision aids are useful
      tools for SDM and have recently been developed for allergen immunotherapy, severe
      asthma, and atopic dermatitis. CONCLUSION: Effective SDM has been shown to
      improve adherence and lead to better outcomes. SDM should be universally
      implemented as a key component of patient-centered health care. Allergy health
      care providers should work with their patients to reach treatment decisions that
      align with their values and preferences.

PMID- 30201471
TI  - Modification of lifestyle behaviour during pregnancy for prevention of childhood
      obesity.

PMID- 30201472
TI  - Benefits of spinal anesthesia for urologic surgery in the youngest of patients.
AB  - INTRODUCTION: Increasing concerns regarding potential negative effects of early
      use of inhalational and intravenous anesthetics on neurocognitive development
      have led to a growing interest in alternative forms of anesthesia in infants. The
      study institution's outcomes with spinal anesthesia (SA) for urologic surgery in
      infants aged less than 90 days are reported and their outcomes with a matched
      cohort of patients who underwent general anesthesia (GA) are compared. METHODS:
      This is a retrospective single-center analysis. Patients aged less than 90 days
      who underwent SA for four urologic surgeries (inguinal hernia repair, scrotal
      exploration, posterior urethral valve ablation, and ureterocele puncture) were
      identified from the study institution's SA database. An age- and procedure
      matched control cohort was identified from a list of patients who underwent the
      aforementioned four procedures under GA since 2013. Outcomes of interest included
      success rate of SA, complications from spinal placement, narcotic use, need for
      supplemental medications and oxygen, and length of hospital stay. RESULTS: Forty
      patients were identified; 20 in the SA and 20 in the GA group. Mean patient age
      was 54 (standard deviation, 35) days. There were no significant differences
      between the groups in age, gender, weight, history of prematurity, or presence of
      comorbidities. Eighty percent of SA patients had successful SA; reasons for
      conversion to GA included failure of spinal needle placement (75%) and agitation
      during operative procedure (25%). Ninety-six percent of patients who received GA
      (primarily or converted) had an endotracheal tube (ETT) placed. No patient in the
      SA group had a complication from spinal needle placement. Patients in the SA
      group were less likely to receive narcotics during the operative procedure (P =
      0.001) and also had a lower mean morphine equivalent dose/kilogram (P = 0.002).
      Patients in the SA group were also less likely to receive any supplemental
      medications during the operative procedure (P = 0.001), particularly intravenous
      corticosteroids (P < 0.001). There were no significant differences in the length
      of hospital stay. CONCLUSIONS: The use of SA has clear advantages for this
      medically vulnerable population. For the majority of patients, it obviates the
      need for ETT placement and airway management and avoids the potential negative
      effects of GA on neurocognitive development. It also decreases the use of
      narcotics and other supplemental medications. In scenarios in which the benefit
      of surgery must be weighed against the risk of GA, such as neonatal torsion, SA
      may allow a paradigm shift in the timing of surgery.

PMID- 30201473
TI  - Time course of the use of chromatic and achromatic facial information for sex
      categorization.
AB  - The most useful facial features for sex categorization are the eyes, the
      eyebrows, and the mouth. Dupuis-Roy et al. reported a large positive correlation
      between the use of the mouth region and rapid correct answers [Journal of Vision
      9 (2009) 1-8]. Given the chromatic information in this region, they hypothesized
      that the extraction of chromatic and achromatic cues may have different time
      courses. Here, we tested this hypothesis directly: 110 participants categorized
      the sex of 300 face images whose chromatic and achromatic content was partially
      revealed through time (200 ms) and space using randomly located spatio-temporal
      Gaussian apertures (i.e. the Bubbles technique). This also allowed us to directly
      compare, for the first time, the relative importance of chromatic and achromatic
      facial cues for sex categorization. Results showed that face-sex categorization
      relies mostly on achromatic (luminance) information concentrated in the eye and
      eyebrow regions, especially the left eye and eyebrow. Additional analyses
      indicated that chromatic information located in the mouth/philtrum region was
      used earlier-peaking as early as 35 ms after stimulus onset-than achromatic
      information in the eye regions-peaking between 165 and 176 ms after stimulus
      onset-as was speculated by Dupuis-Roy et al. A non-linear analysis failed to
      support Yip and Sinha's proposal that processing of chromatic variations can
      improve subsequent processing of achromatic spatial cues, possibly via surface
      segmentation [Perception 31 (2002) 995-1003]. Instead, we argue that the brain
      prioritizes chromatic information to compensate for the sluggishness of chromatic
      processing in early visual areas, and allow chromatic and achromatic information
      to reach higher-level visual areas simultaneously.

PMID- 30201474
TI  - Profile of off-axis higher order aberrations and its variation with time among
      various refractive error groups.
AB  - Peripheral higher order aberrations (HOA) of 646 children at 30 degrees 
      temporal, nasal and inferior visual field were measured under cycloplegia (5 mm
      pupil diameter) using a commercially available Shack-Hartmann aberrometer in the
      Sydney Myopia Study [age, 12.7 +/- 0.4 years (mean +/- standard deviation)] and
      five years later in the Sydney Adolescent Vascular and Eye Study. At baseline,
      176 eyes were emmetropic, 95 were myopic and 375 were hyperopic. Coma, 3rd order
      and RMS of coma increased with eccentricity for all eyes and no difference was
      observed for 4th order and RMS of C(4,0) among refractive error groups. More
      positive C(4,0) was observed for hyperopic eyes at periphery. At follow up, 26%
      had 'myopic change' and 70% had 'no change' in refractive error. At follow-up,
      horizontal coma became more negative at nasal field and more positive at temporal
      field for all eyes. More positive C(4,0) for hyperopic eyes at baseline may
      indicate variation in optical characteristics of peripheral cornea and
      crystalline lens. An increase in horizontal coma with time, irrespective of
      refractive error change, may be attributed to variation in the shape factor of
      peripheral cornea and crystalline lens and/or misalignment of optical
      surfaces/components relative to the visual axis (angle kappa) as the eye grows in
      axial length.

PMID- 30201470
TI  - Influence of maternal obesity on the association between common pregnancy
      complications and risk of childhood obesity: an individual participant data meta
      analysis.
AB  - BACKGROUND: Gestational diabetes and gestational hypertensive disorders are
      associated with offspring obesity, but the role of maternal adiposity in these
      associations remains unclear. We aimed to investigate whether these pregnancy
      complications affect the odds of offspring obesity independently of maternal
      obesity. METHODS: We did an individual participant data (IPD) meta-analysis of
      mother-offspring pairs from prospective birth cohort studies that had IPD on
      mothers with singleton liveborn children born from 1989 onwards and had
      information available about maternal gestational diabetes, gestational
      hypertension or pre-eclampsia, and childhood body-mass index (BMI). We applied
      multilevel mixed-effects models to assess associations of gestational diabetes,
      gestational hypertension, and pre-eclampsia with BMI SD scores and the odds of
      overweight and obesity throughout childhood, adjusting for lifestyle
      characteristics (offspring's sex, maternal age, educational level, ethnicity,
      parity, and smoking during pregnancy). We then explored the extent to which any
      association was explained by maternal pre-pregnancy or early-pregnancy BMI.
      FINDINGS: 160 757 mother-offspring pairs from 34 European or North American
      cohorts were analysed. Compared with uncomplicated pregnancies, gestational
      diabetes was associated with increased odds of overweight or obesity throughout
      childhood (odds ratio [OR] 1.59 [95% CI 1.36 to 1.86] for early childhood [age
      2.0-4.9 years], 1.41 [1.26 to 1.57] for mid childhood [5.0-9.9 years], and 1.32
      [0.97 to 1.78] for late childhood [10.0-17.9 years]); however, these associations
      attenuated towards the null following adjustment for maternal BMI (OR 1.35 [95%
      CI 1.15 to 1.58] for early childhood, 1.12 [1.00 to 1.25] for mid childhood, and
      0.96 [0.71 to 1.31] for late childhood). Likewise, gestational hypertension was
      associated with increased odds of overweight throughout childhood (OR 1.19 [95%
      CI 1.01 to 1.39] for early childhood, 1.23 [1.15 to 1.32] for mid childhood, and
      1.49 [1.30 to 1.70] for late childhood), but additional adjustment for maternal
      BMI largely explained these associations (1.01 [95% CI 0.86 to 1.19] for early
      childhood, 1.02 [0.95 to 1.10] for mid childhood, and 1.18 [1.03 to 1.36] for
      late childhood). Pre-eclampsia was associated with decreased BMI in early
      childhood only (difference in BMI SD score -0.05 SD score [95% CI -0.09 to 
      0.01]), and this association strengthened following additional adjustment for
      maternal BMI. INTERPRETATION: Although lowering maternal risk of gestational
      diabetes, gestational hypertension, and pre-eclampsia is important in relation to
      maternal and fetal pregnancy outcomes, such interventions are unlikely to have a
      direct impact on childhood obesity. Preventive strategies for reducing childhood
      obesity should focus on maternal BMI rather than on pregnancy complications.
      FUNDING: EU's Horizon 2020 research and innovation programme (LifeCycle Project).

PMID- 30201475
TI  - Comment on "Volvulus of the sigmoid colon is associated with hypotrophy of the
      left lateral segment of the liver and the absence of sigmoid diverticulum".

PMID- 30201476
TI  - Safety of biological agents in paediatric rheumatic diseases: A real-life
      multicenter retrospective study using the JIRcohorte database.
AB  - OBJECTIVE: To analyse and report the incidence of side effects of biological
      agents in paediatric patients with inflammatory diseases using of real-life
      follow-up cohort. METHODS: In this international, observational, retrospective,
      multicentre study of children treated by biological agents and followed in the
      Juvenile Inflammatory Rheumatism (JIR) cohort (JIRcohorte) network, a Kaplan
      Meier method was used to estimate the occurrence of adverse events. A Cox model
      was constructed to identify independent predictors of adverse events. RESULTS:
      Overall 813 patients totalling 3439 patients-year (PY) of biological agents were
      included. The main diagnosis was juvenile idiopathic arthritis (84%). A total of
      222 patients (27.3%) had 419 adverse events, representing an incidence rate of
      12.2 per 100 PY 95% CI [11.0; 13.4]. The overall incidence rate of serious
      adverse events was 3.9 per 100 PY 95% CI [3.2; 4.6]. Tocilizumab and infliximab
      were significantly associated with adverse events and canakinumab with serious
      adverse events. Univariate and multivariable analysis of adverse events and
      serious adverse events indicated that patients under biological agents with
      concomitant immunosuppressive drugs (excluding methotrexate) suffered from more
      of these events. CONCLUSION: This study suggests an overall an acceptable safety
      of biologic agents in children with inflammatory rheumatic diseases treated with
      biological agents. However, the concomitant prescription of immunosuppressive
      drugs with biological agents represents a substantial risk of adverse events.

PMID- 30201477
TI  - Intraarticular synovial osteochondromatosis of the elbow joint with radial nerve
      palsy.

PMID- 30201478
TI  - Targeted immunotherapy strategies in ANCA-associated vasculitis.
AB  - Targeted immunotherapy is substantially improving the management of ANCA
      associated vasculitides (AAV), which include granulomatosis with polyangiitis
      (GPA, Wegener's granulomatosis), microscopic polyangiitis (MPA), and eosinophilic
      granulomatosis with polyangiitis (EGPA, Churg-Strauss syndrome). This article
      reviews the current role for targeted immunotherapy in AAV, its validated
      indications, and avenues for further development. Rituximab is a validated
      induction treatment for GPA and severe MPA. Rituximab in these indications is not
      less effective than cyclophosphamide and is particularly useful in patients with
      refractory or relapsing disease, women of childbearing potential, and patients
      previously treated with cyclophosphamide. Rituximab is more effective than
      cyclophosphamide for treating relapses. For remission maintenance therapy, which
      is indispensable, rituximab has been proven superior over conventional
      immunosuppressive treatment. Rituximab is licensed in the USA and in Europe for
      the induction treatment of severe forms of GPA and MPA. An extension study for
      remission maintenance therapy is ongoing. In EGPA, although maintenance treatment
      with the interleukin-5 antagonist mepolizumab is effective in decreasing
      glucocorticoid requirements and in alleviating asthma and sinonasal symptoms, its
      efficacy on the vasculitis remains somewhat unclear. Mepolizumab is licensed for
      use in EGPA, and rituximab is also being evaluated as an induction and
      maintenance agent. Immunoglobulins can be helpful as an adjuvant treatment for
      active AAV with severe immunedepression, notably when infections occur. Plasma
      exchange is indicated in AAV with advanced renal dysfunction and, perhaps, in the
      event of alveolar hemorrhage, a possibility that will be assessed in 2018 in a
      large international study.

PMID- 30201479
TI  - Hip Disease Complicating Myelitis.

PMID- 30201480
TI  - Percutaneous versus surgical pulmonic valve implantation for right ventricular
      outflow tract dysfunction.
AB  - BACKGROUND/PURPOSE: Percutaneous pulmonic valve implantation (PPVI) is an
      alternative treatment strategy to surgical pulmonic valve implantation (SPVI) for
      right ventricular outflow tract (RVOT) dysfunction. This study sought to compare
      outcomes of both treatment strategies. METHODS: The study population was
      extracted from the 2014 Nationwide Readmissions Database (NRD) using
      International Classification of Diseases, Ninth Revision, Clinical Modification
      (ICD-9-CM) codes for PPVI and SPVI. Study outcomes included all-cause in-hospital
      mortality, length of index hospital stay (LOS), post-procedural bleeding,
      mechanical complications of heart valve prosthesis, vascular complications (VC),
      infective endocarditis (IE), total hospitalization charges, and 30-day
      readmission rates. RESULTS: A total of 975 patient discharges (176 in PPVI and
      799 in SPVI group) were identified (average age 25.7 years; 57.5% male). PPVI was
      associated with significantly shorter median LOS (1 versus 5 days, p < 0.01),
      lower risk of bleeding (4.6% versus 26.4%, p < 0.01), and lower total
      hospitalization charges ($169,551.7 versus $210,681.8, p = 0.02). There was no
      significant difference between both groups in terms of all-cause in-hospital
      mortality (0% versus 1.4%, p = 0.12), mechanical complications of heart valve
      prosthesis (1.7% versus 2.0%, p = 0.78), VC (2.3% versus 2.0%, p = 0.82), IE
      (1.7% versus 3.1%, p = 0.31), or 30-day readmission rates (4.4% versus 7.6%, p =
      0.16). CONCLUSION: Compared with SPVI, PPVI was associated with shorter LOS,
      lower bleeding, and lower total charges. There was no significant difference
      between the two strategies in terms of all-cause in-hospital mortality,
      mechanical complications of heart valve prosthesis, VC, IE, or 30-day readmission
      rates.

PMID- 30201481
TI  - Outcomes after atherectomy treatment of severely calcified coronary bifurcation
      lesions: A single center experience.
AB  - BACKGROUND: Coronary bifurcation and calcified lesions account for 15-20% and 6%
      20% of percutaneous coronary interventions (PCI), respectively. Treatment of
      these lesions is associated with high periprocedural complication rates and
      unfavorable long-term clinical outcomes, including high rates of
      revascularization. This retrospective, single-center study evaluated the outcomes
      of atherectomy treatment for heavily calcified coronary bifurcation lesions.
      METHODS: Patients who underwent a coronary atherectomy procedure to treat a
      heavily calcified lesion between January 2010 and March 2016 at Metropolitan
      Heart and Vascular Institute (Minneapolis, MN) were included in this
      retrospective study. Data were stratified to compare atherectomy treatment of
      coronary bifurcation lesions vs non-bifurcation lesions. Additionally, data were
      compared based on type of atherectomy utilized during the index procedure, either
      orbital (OAS) or rotational (RA) atherectomy. Major adverse cardiac events
      (MACE), defined as a composite of death, myocardial infarction (MI), and target
      vessel revascularization (TVR), were assessed at 30 days post-procedure. RESULTS:
      Among the 177 patients treated with atherectomy, 72 patients had bifurcation
      lesions. Compared to patients with non-bifurcation lesions, patients with
      bifurcation lesions were more likely to have a history of prior PCI or coronary
      artery bypass grafting. Bifurcation lesions required a higher volume of contrast.
      There were similar low rates of slow flow/no-reflow (2.8% bifurcations vs 1.0%
      non-bifurcation; p = 0.355). The 30-day rates of death (1.4% vs 1.9%; p = 0.794),
      MI (0% vs 0%; p = NA), and TVR (0% vs 1.0%; p = 0.406) were similar in patients
      with bifurcation lesions versus those without, respectively. An atherectomy sub
      analysis (OAS vs RA) of the patients with bifurcation lesions showed that OAS
      utilization was associated with shorter procedure time (81 min vs 109 min; p =
      0.026) and fluoroscopy time (18 min vs 27 min; p = 0.007) compared to RA,
      respectively-no significant differences in baseline demographic or lesion
      characteristics were noted in the bifurcation atherectomy sub-groups, except for
      higher beta/calcium blocker use in RA bifurcation subjects. CONCLUSIONS: The
      results of this study demonstrated that atherectomy treatment in patients with
      heavily calcified coronary bifurcation lesions is feasible, resulting in similar
      low 30-day MACE rates as compared to patients with non-bifurcation lesions. In
      addition, in this study OAS utilization versus RA in bifurcation lesions was
      associated with significantly shorter procedure and fluoroscopy time. Further
      studies are needed to assess the safety and efficacy of atherectomy in patients
      with severely calcified bifurcation lesions. SUMMARY FOR ANNOTATED TABLE OF
      CONTENTS: This retrospective, single-center study evaluated the outcomes of
      orbital and rotational atherectomy treatment for heavily calcified coronary
      bifurcation lesions as compared to non-bifurcation lesions. The results
      demonstrate that atherectomy treatment in patients with heavily calcified
      coronary bifurcation lesions is feasible, resulting in similarly low 30-day MACE
      rates as compared to patients with non-bifurcation lesions. In addition, in this
      study OAS utilization versus RA in bifurcation lesions was associated with
      significantly shorter procedure and fluoroscopy time.

PMID- 30201482
TI  - Moderate developmental alcohol exposure reduces repetitive alternation in a
      zebrafish model of fetal alcohol spectrum disorders.
AB  - The damaging effects of alcohol on a developing fetus are well known and cause a
      range of conditions known as fetal alcohol spectrum disorder (FASD). High levels
      of alcohol exposure lead to physical deformity and severe cognitive deficits, but
      more moderate exposure leads to a range of subtle cognitive effects such as
      reduced social behavior, higher propensity to develop addictions, and reduced
      spatial working memory. Previous studies have demonstrated that following
      exposure to relatively low levels of ethanol during early brain development
      (equivalent in humans to moderate exposure) zebrafish display a range of social
      and behavioral differences. Here, our aim was to test the hypothesis that
      moderate developmental ethanol exposure would affect aspects of learning and
      memory in zebrafish. In order to do this, we exposed zebrafish embryos to 20 mM
      [0.12% v/v] ethanol from 2 to 9 dpf to model the effects of moderate prenatal
      ethanol (MPE) exposure. At 3 months old, adult fish were tested for appetitive
      and aversive learning, and for spatial alternation in a novel unconditioned y
      maze protocol. We found that MPE did not affect appetitive or aversive learning,
      but exposed-fish showed a robust reduction in repetitive alternations in the y
      maze when compared to age matched controls. This study confirms that moderate
      levels of ethanol exposure to developing embryos have subtle effects on spatial
      working memory in adulthood. Our data thus suggest that zebrafish may be a
      promising model system for studying the effects of alcohol on learning and
      decision-making, but also for developing treatments and interventions to reduce
      the negative effects of prenatal alcohol.

PMID- 30201483
TI  - Sustained Release of Minocycline From Minocycline-Calcium-Dextran Sulfate Complex
      Microparticles for Periodontitis Treatment.
AB  - It is important to address the periodontitis-associated bacteria in the residual
      subgingival plaque after scaling and root planing to successfully treat
      periodontitis. In this study, we explored the possibility of exploiting the ion
      pairing/complexation of minocycline, Ca2+, and sulfate/sulfonate-bearing
      biopolymers to develop an intrapocket delivery system of minocycline as an
      adjunct to scaling and root planing. Minocycline-calcium-dextran sulfate complex
      microparticles were synthesized from minocycline, CaCl2, and dextran sulfate.
      They were characterized using Fourier-transform infrared spectroscopy, scanning
      electron microscopy, and energy-dispersive X-ray spectroscopy. An in vitro
      release study was conducted to evaluate the release kinetics of minocycline from
      these microparticles. Agar disk diffusion assays and biofilm-grown bacteria
      assays were used to assess antibacterial capability. High loading efficiency
      (96.98% +/- 0.12%) and high loading content (44.69% +/- 0.03%) for minocycline
      were observed for these complex microparticles. Mino-Ca-DS microparticles
      achieved sustained release of minocycline for at least 9 days at pH 7.4 and 18
      days at pH 6.4 in phosphate-buffered saline, respectively. They also demonstrated
      potent antimicrobial effects against Streptococcus mutans and Aggregatibacter
      actinomycetemcomitans in agar disk diffusion and biofilm assays. These results
      suggested that the ion pairing/complexation of minocycline, Ca2+, and
      sulfonate/sulfate-bearing biopolymers can be exploited to develop complex
      microparticles as local delivery systems for periodontitis treatment.

PMID- 30201484
TI  - Advance Care Planning Needs in Patients With Glioblastoma Undergoing
      Radiotherapy.

PMID- 30201485
TI  - Defining Core Competencies for Generalist-Level Palliative Social Work.
AB  - CONTEXT: Care provided to seriously ill patients by frontline social workers is a
      component of generalist-level palliative care. The core competencies for high
      quality generalist-level palliative social work are necessary to promote training
      curricula and best practices but have not yet been defined in the U.S. OBJECTIVE:
      The objective of this study was to develop consensus-derived core competencies
      for generalist-level palliative social work. METHODS: Fifty-five proposed social
      work competencies were categorized by the eight domains of palliative care
      identified by the National Consensus Project for Quality Palliative Care. The
      competencies were rated by 41 regionally dispersed, Master's level social workers
      selected through purposive and snowball sampling using a Delphi method. Each was
      rated as essential for generalist-level palliative social work, acceptable with
      modifications, or rejected based on the judgment that it was not essential for
      generalist-level palliative social work or was outside the scope of practice.
      Consensus was defined as >70% agreement to accept or reject a competency. Three
      review rounds were needed to achieve consensus on all competencies. RESULTS: Two
      competencies were added to the original list. Of the 57 proposed competencies, 41
      were accepted (19 after modification) and 16 were rejected. Competencies in the
      social, spiritual, cultural, and ethical/legal aspects of care domains were
      relatively more likely to be accepted compared with those in structure and
      processes of care, physical care, psychological care, and care of patient at the
      end of life. CONCLUSION: The 41 consensus-derived competencies for generalist
      level palliative social work may inform the development of training curricula and
      standards for high-quality care.

PMID- 30201486
TI  - Breakthrough Medication in Unresponsive Palliative Care Patients: Indications,
      Practice, and Efficacy.
AB  - CONTEXT: An unresponsive patient's need and their response to breakthrough
      medication is determined by clinical assessment and/or observational measures.
      How closely these methods match the patient's experience is unknown. OBJECTIVES:
      Determine the efficacy and effectiveness of breakthrough medication in
      unresponsive patients and the perception of patient comfort made by nurses and
      family. METHODS: A prospective study of breakthrough medication in unresponsive
      patients. The Richmond Agitation-Sedation Scale (RASS) and Patient Comfort Score
      (PCS) were compared with time-matched Bispectral Index (BIS) Scores. The effects
      of opioid vs. opioid + benzodiazepine breakthroughs and the relation between
      synchronous nurse and family measurements of the PCS were evaluated. Analysis of
      variance and paired t-tests were used for BIS analyses and nonparametric Mann
      Whitney tests for RASS and PCS. RESULTS: Significant reductions at 30 and 60
      minutes after breakthrough medication were noted for BIS (P < 0.0004), RASS (P =
      0.043 and 0.004, respectively), and PCS (P < 0.0004). A direct comparison of the
      effect of opioid breakthrough medication vs. opioid plus benzodiazepine revealed
      no significant difference (BIS, P = 0.512; RASS, P = 0.195; PCS, P = 0.119). Of
      the 157 synchronous nurse and family measures of patient comfort, families rated
      patient discomfort significantly higher than nurses (P < 0.0004). CONCLUSION:
      This study provides additional evidence for the efficacy and effectiveness of
      breakthrough medication and the merit of observational measures in determining a
      patient's response. The onset of action is evident at 30 minutes after injection.
      Family assessment of patient comfort may be more nuanced than that of nurses, and
      they not uncommonly rate patient discomfort higher than nurses.

PMID- 30201487
TI  - Spiritual Well-being Among Palliative Care Patients With Different Religious
      Affiliations: A Multicenter Korean Study.
AB  - CONTEXT: Spiritual well-being (SWB) is very important in palliative care
      patients. OBJECTIVES: The aim of this study was to investigate the SWB among
      palliative care patients in Korea with different religious affiliations and to
      identify the correlates of SWB. METHODS: This study is a cross-sectional,
      multicenter study involving hospitalized patients seen by palliative care teams.
      We collected data on basic clinicodemographic characteristics, factors related to
      religion (meaningful religious events, religious activities such as attending
      worship, individual spiritual activities such as prayer), overall quality of
      life, and SWB. SWB was measured using Functional Assessment of Chronic Illness
      Therapy-Spirituality 12. We examined the differences in SWB among patients who
      reported themselves as Protestants, Catholics, Buddhists, and having no religious
      affiliations. RESULTS: Among the 202 patients enrolled, 69 (34.2%), 48 (23.8%),
      43 (21.3%), and 42 (20.8%) persons were Protestants, were Catholics, were
      Buddhists, and had no religious affiliation, respectively. The Functional
      Assessment of Chronic Illness Therapy-Spirituality 12 was highest among
      Protestants, followed by Catholics, Buddhists, and those without religious
      affiliation (29.8 vs. 27.0 vs. 23.2 vs. 16.3, P < 0.001). The faith subscale
      (12.4 vs. 10.4 vs. 7.7 vs. 2.5, P < 0.001) showed similar distributions.
      Christians reported higher SWB in the meaning and the peace subscale than
      patients without a religious affiliation. In the multivariate analysis, religious
      affiliation (P < 0.001), individual spiritual activities (P < 0.001), and quality
      of life (P < 0.001) were significantly related to a greater SWB. Age was
      inversely associated with the meaning subscale (P = 0.002). CONCLUSION: Although
      faith practices may be particularly helpful to improve spiritual well-being among
      Christians, further research is needed to determine what individual spiritual
      activities can support non-Christians.

PMID- 30201488
TI  - Machine learning approaches in GIS-based ecological modeling of the sand fly
      Phlebotomus papatasi, a vector of zoonotic cutaneous leishmaniasis in Golestan
      province, Iran.
AB  - The distribution and abundance of Phlebotomus papatasi, the primary vector of
      zoonotic cutaneous leishmaniasis in most semi-/arid countries, is a major public
      health challenge. This study compares several approaches to model the spatial
      distribution of the species in an endemic region of the disease in Golestan
      province, northeast of Iran. The intent is to assist decision makers for targeted
      interventions. We developed a geo-database of the collected Phlebotominae sand
      flies from different parts of the study region. Sticky paper traps coated with
      castor oil were used to collect sand flies. In 44 out of 142 sampling sites, Ph.
      papatasi was present. We also gathered and prepared data on related environmental
      factors including topography, weather variables, distance to main rivers and
      remotely sensed data such as normalized difference vegetation cover and land
      surface temperature (LST) in a GIS framework. Applicability of three classifiers:
      (vanilla) logistic regression, random forest and support vector machine (SVM)
      were compared for predicting presence/absence of the vector. Predictive
      performances were compared using an independent dataset to generate area under
      the ROC curve (AUC) and Kappa statistics. All three models successfully predicted
      the presence/absence of the vector, however, the SVM classifier (Accuracy =
      0.906, AUC = 0.974, Kappa = 0.876) outperformed the other classifiers on
      predicting accuracy. Moreover, this classifier was the most sensitive (85%), and
      the most specific (93%) model. Sensitivity analysis of the most accurate model
      (i.e. SVM) revealed that slope, nighttime LST in October and mean temperature of
      the wettest quarter were among the most important predictors. The findings
      suggest that machine learning techniques, especially the SVM classifier, when
      coupled with GIS and remote sensing data can be a useful and cost-effective way
      for identifying habitat suitability of the species.

PMID- 30201489
TI  - Engineering the niche for hair regeneration - A critical review.
AB  - Recent progress in hair follicle regeneration and alopecia treatment necessitates
      revisiting the concepts and approaches. In this sense, there is a need for
      shedding light on the clinical and surgical therapies benefitting from
      nanobiomedicine. From this perspective, this review attempts to recognize
      requirements upon which new hair therapies are grounded; to underline
      shortcomings and opportunities associated with recent advanced strategies for
      hair regeneration; and most critically to look over hair regeneration from
      nanomaterials and pluripotent stem cell standpoint. It is noteworthy that
      nanotechnology is able to illuminate a novel path for reprogramming cells and
      controlled differentiation to achieve the desired performance. Undoubtedly, this
      strategy needs further advancement and a lot of critical questions have yet to be
      answered. Herein, we introduce the salient features, the hurdles that must be
      overcome, the hopes, and practical constraints to engineer stem cell niches for
      hair follicle regeneration.

PMID- 30201490
TI  - Guiding principles for mechanistic modeling of bispecific antibodies.
AB  - System based pharmacokinetic (PK) models can be used to study and predict the
      distribution of antibody based drugs into target tissues and assess the
      pharmacobinding (PB) of the drug to the target and the subsequent pharmacodynamic
      (PD) changes. In the absence of relevant PD readouts, compounded in cases of
      novel mechanisms, one can rely on binding between the drug and the target,
      computed as target occupancy (TO), as a relevant biomarker. This approach assumes
      that at maximum TO across the dosing interval, the drug-target interaction must
      demonstrate the intended pharmacology. Such analysis can help set laboratory
      objectives for protein engineers and chemists and guide them to the appropriate
      design and binding affinity of the molecule. Analysis of mechanistic models to
      guide affinity optimization against soluble and membrane-bound targets has been
      done for monoclonal antibodies (mAbs) (Tiwari et al., The AAPS Journal, 2017).
      However, comparable understanding of bispecific antibodies (BsAb; drugs with two
      targets, which are either soluble, membrane-bound, or a combination of the two)
      is still lacking. We propose to extend the work done by Tiwari et al. (2017) to
      BsAb. We focus on describing a generic BsAb with two membrane-bound targets, and
      explore the impact of various parameters on the TO of the BsAb to each target.
      Performed analysis can guide the optimization of dissociation constant (KD) of
      the BsAb, and can also help in identifying druggable targets. Proposed model can
      be modified and tailored to specific biologics as needed.

PMID- 30201492
TI  - IL-37 diminishes proteoglycan loss in human OA cartilage: donor-specific link
      between IL-37 and MMP-3.
AB  - OBJECTIVE: A hallmark of osteoarthritis (OA) is degradation of articular
      cartilage proteoglycans. In isolated human OA chondrocytes, the anti-inflammatory
      cytokine Interleukin-37 (IL-37) lowers the expression of the proteolytic MMP and
      ADAMTS enzymes, which mediate this degradation. Therefore, we investigated if IL
      37 protects against proteoglycan loss in freshly obtained human OA explants.
      MATERIAL AND METHODS: Human OA cartilage explants were incubated with IL-37.
      Release of sulphated proteoglycans (sGAGs) was measured with the
      dimethylmethylene-blue assay. Production and degradation of newly synthesized
      proteoglycans was measured using 35S-sulphate. Proteoglycan and proteolytic
      enzyme expression were analyzed by qPCR and Western Blot. Proteolytic activity
      was determined by measuring MMP- and ADAMTS-generated aggrecan neo-epitopes with
      ELISA and by using MMP-3-, MMP-13- or ADAMTS-5-inhibitors. RESULTS: Over time, a
      linear release of sGAGs from OA cartilage was measured. IL-37 reduced this
      release by 87 MUg/ml (24%) 95%CI [21.04-141.4]. IL-37 did not affect 35S-sulphate
      incorporation or proteoglycan gene expression. In contrast, IL-37 reduced loss of
      35S-sulphate labeled GAGs and reduced MMP-3 protein expression, indicating that
      IL-37 inhibits proteoglycan degradation. Remarkably, we observed two groups of
      patients; one group in which MMP-3-inhibition lowered sGAG release, and one group
      in which ADAMTS5-inhibition had this effect. Remarkably, IL-37 was only
      functional in the group of patients that responded to MMP-3-inhibition.
      CONCLUSION: We identified a relationship between IL-37 and reduced sGAG loss in
      OA cartilage. Most likely, this effect is mediated by inhibition of MMP-3
      expression. These results suggest that IL-37 could be applied as therapy in a
      subgroup of OA patients, in which cartilage degradation is mediated by MMP-3.

PMID- 30201491
TI  - A novel FGFR1-binding peptide attenuates the degeneration of articular cartilage
      in adult mice.
AB  - OBJECTIVE: We previously reported that genetic ablation of (Fibroblast Growth
      Factors Receptors) FGFR1 in knee cartilage attenuates the degeneration of
      articular cartilage in adult mice, which suggests that FGFR1 is a potential
      targeting molecule for osteoarthritis (OA). Here, we identified R1-P1, an
      inhibitory peptide for FGFR1 and investigated its effect on the pathogenesis of
      OA in mice induced by destabilization of medial meniscus (DMM). DESIGN: Binding
      ability between R1-P1 and FGFR1 protein was evaluated by enzyme-linked immuno
      sorbent assay (ELISA) and molecular docking. Alterations in cartilage were
      evaluated histologically. The expression levels of molecules associated with
      articular cartilage homeostasis and FGFR1 signaling were analyzed by quantitative
      real-time polymerase chain reaction (qRT-PCR), Western blotting and
      immunohistochemistry (IHC). The chondrocyte apoptosis was detected by terminal
      deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) assay. RESULTS:
      R1-P1 had highly binding affinities to human FGFR1 protein, and efficiently
      inhibited extracellular signal-regulated kinase (ERK)1/2 pathway in mouse primary
      chondrocytes. In addition, R1-P1 attenuated the IL-1beta induced significant loss
      of proteoglycan in full-thickness cartilage tissue from human femur head.
      Moreover, this peptide can significantly restore the IL-1beta mediated loss of
      proteoglycan and type II collagen (Col II) and attenuate the expression of matrix
      metalloproteinase-13 (MMP13) in mouse primary chondrocytes. Finally, intra
      articular injection of R1-P1 remarkably attenuated the loss of proteoglycan and
      the destruction of articular cartilage and decreased the expressions of
      extracellular matrix (ECM) degrading enzymes and apoptosis in articular
      chondrocytes of mice underwent DMM surgery. CONCLUSIONS: R1-P1, a novel
      inhibitory peptide for FGFR1, attenuates the degeneration of articular cartilage
      in adult mice, which is a potential leading molecule for the treatment of OA.

PMID- 30201493
TI  - APOL1-miR-193 Axis as a Bifunctional Regulator of the Glomerular Parietal
      Epithelium: Maintaining Parietal Cell Phenotype versus Promoting Podocyte
      Differentiation.
AB  - This commentary highlights the article by Kumar et al that reports an essential
      role of APOL1 in maintaining podocyte phenotype.

PMID- 30201494
TI  - High Frequency of beta-Catenin Mutations in Mouse Hepatocellular Carcinomas
      Induced by a Nongenotoxic Constitutive Androstane Receptor Agonist.
AB  - Activation of Wnt/beta-catenin signaling is frequent in human and rodent
      hepatocarcinogenesis. Although in mice the tumor-promoting activity of agonists
      of constitutive androstane receptor (CAR) occurs by selection of carcinogen
      initiated cells harboring beta-catenin mutations, the molecular alterations
      leading to hepatocellular carcinoma (HCC) development by the CAR agonist 1,4
      bis[2-(3,5-dichloropyridyloxy)]benzene (TCP) in the absence of genotoxic injury
      are unknown. Here, we show that CAR activation per se induced HCC in mice and
      that 91% of them carried beta-catenin point mutations or large in-frame
      deletions/exon skipping targeting Ctnnb1 exon 3. Point mutations in HCCs induced
      by TCP alone displayed different nucleotide substitutions compared with those
      found in HCCs from mice pretreated with diethylnitrosamine. Moreover, unlike
      those occurring in HCCs from diethylnitrosamine + TCP mice, they did not result
      in increased expression of beta-catenin target genes, such as Glul, Lgr5, Rgn,
      Lect2, Tbx3, Axin2, and Ccnd1, or nuclear translocation of beta-catenin compared
      with the control liver. Remarkably, in the nontumoral liver tissue, chronic CAR
      activation led to down-regulation of these genes and to a partial loss of
      glutamine synthetase-positive hepatocytes. These results show that, although
      chronic CAR activation per se induces HCCs carrying beta-catenin mutations, it
      concurrently down-regulates the Wnt/beta-catenin pathway in nontumoral liver.
      They also indicate that the relationship between CAR and beta-catenin may be
      profoundly different between normal and neoplastic hepatocytes.

PMID- 30201496
TI  - Characterization of Glomerular Sox9+ Cells in Anti-Glomerular Basement Membrane
      Nephritis in the Rat.
AB  - Mechanisms of glomerular crescent formation and podocyte repair processes are
      still unclear. Therefore, we investigated the expression of the transcription
      factor Sox9 as a potential marker of a subpopulation of parietal epithelial cells
      (PECs) with potential regenerative properties. Glomerular Sox9 expression was
      characterized in detail in a rat anti-glomerular basement membrane (GBM)
      nephritis model using immunofluorescence and confocal laser scanning microscopy.
      In healthy kidneys Sox9 is expressed in a subpopulation of PECs restricted to
      approximately 20% to 50% of PEC nuclei and was highly conserved in all
      investigated species. During rat anti-GBM nephritis the number of glomerular
      Sox9+ cells increased and was associated with proliferation activity. In
      nephritic glomeruli Sox9 expression was not restricted to Bowman's capsule lining
      but was also found on cells of the glomerular tuft. Nearly all Sox9+ cells also
      expressed the PEC marker Pax8, whereas endothelial cells, mesangial cells,
      macrophages, and T lymphocytes lacked Sox9 expression. At the margins of
      crescents Sox9+/Pax8+ cells additionally expressed podocyte markers. In contrast,
      in sclerotic lesions a minority of Sox9+/Pax8+ cells expressed the myofibroblast
      marker alpha-smooth muscle actin. In glomerular Sox9+ cells Jagged 1 was up
      regulated. During anti-GBM nephritis Sox9+ PECs proliferate and migrate onto the
      glomerular tuft. Future studies are needed to confirm the origin of Sox9+ cells
      from PECs and differentiation in both podocytes and/or myofibroblasts.

PMID- 30201495
TI  - Role of Apolipoprotein L1 in Human Parietal Epithelial Cell Transition.
AB  - Human parietal epithelial cells (PECs) are progenitor cells that sustain podocyte
      homeostasis. We hypothesized that the lack of apolipoprotein (APO) L1 ensures the
      PEC phenotype, but its induction initiates PEC transition (expression of podocyte
      markers). APOL1 expression and down-regulation of miR193a coincided with the
      expression of podocyte markers during the transition. The induction of APOL1 also
      stimulated transition markers in human embryonic kidney cells (cells with
      undetectable APOL1 protein expression). APOL1 silencing in PECs up-regulated
      miR193a expression, suggesting the possibility of a reciprocal feedback
      relationship between APOL1 and miR193a. HIV, interferon-gamma, and vitamin D
      receptor agonist down-regulated miR193a expression and induced APOL1 expression
      along with transition markers in PECs. Luciferase assay suggested a putative
      interaction between miR193a and APOL1. Since silencing of APOL1 attenuated HIV-,
      vitamin D receptor agonist-, miR193a inhibitor-, and interferon-gamma-induced
      expression of transition markers, APOL1 appears to be a critical functional
      constituent of the miR193a- APOL1 axis in PECs. This notion was confirmed by
      further enhanced expression of PEC markers in APOL1 mRNA-silenced PECs. In vivo
      studies, glomeruli in patients with HIV, and HIV/APOL1 transgenic mice had foci
      of PECs expressing synaptopodin, a transition marker. APOL1 likely regulates PEC
      molecular phenotype through modulation of miR193a expression, and APOL1 and
      miR193a share a reciprocal feedback relationship.

PMID- 30201497
TI  - Global and Targeted miRNA Expression Profiling in Clear Cell Renal Cell Carcinoma
      Tissues Potentially Links miR-155-5p and miR-210-3p to both Tumorigenesis and
      Recurrence.
AB  - About 30% of patients undergoing nephrectomy for renal cell carcinoma (RCC)
      experience disease recurrence. We profiled miRNAs dysregulated in clear-cell (cc)
      RCC tumor tissues and predictive of recurrence. The expression levels of 800
      miRNAs were assessed in paired tumor and normal tissues from a discovery cohort
      of 18 ccRCC patients. miRNAs found to be differentially expressed were examined
      in a validation set of 205 patients, using real-time quantitative PCR. Tumor
      normal data from 64 patients in The Cancer Genome Atlas were used for external
      validation. Twenty-eight miRNAs were consistently dysregulated in tumor tissues.
      On dichotomized analysis, patients with high levels of miR-155-5p and miR-210-3p
      displayed an increased risk for ccRCC recurrence (hazard ratio, 2.64; 95% CI,
      1.49 to 4.70; P = 0.0009; and hazard ratio, 1.80; 95% CI, 1.04 to 3.12; P =
      0.036, respectively) and a shorter median recurrence-free survival time than did
      patients with low levels [P < 0.01 (log rank test)]. A risk score was generated
      based on the expression levels of miR-155-5p and miR-210-3p, and the trend test
      was significant (P = 0.005). On pathway analysis, target genes regulated by miR
      155-5p and miR-210-3p were mainly enriched in inflammation-related pathways. We
      identified and validated multiple miRNAs dysregulated in ccRCC tissues; miR-155
      5p and miR-210-3p were predictive of ccRCC recurrence, pointing to potential
      utility as biomarkers and underlying biological mechanisms.

PMID- 30201498
TI  - The Role of Neonatal Gr-1+ Myeloid Cells in a Murine Model of Rhesus-Rotavirus
      Induced Biliary Atresia.
AB  - Activation of innate immunity together with cholangiocyte damage occurs in
      biliary atresia (BA). However, detailed information on the inflammatory cells
      involved is lacking. This study investigates both the pathophysiology of CD11b+Gr
      1+ cells in a mouse model of BA and their presence in BA patients. CD11b+Gr-1+
      cells were targeted by an anti-Ly6G antibody in murine BA induced by inoculation
      with rhesus rotavirus. Expression of the Ly6G homolog CD177+ was examined in
      biopsies from BA patients. The symptoms of BA were ameliorated, and survival was
      prolonged in those mice receiving 5 to 10 MUg of antibody per mouse every 3 days
      for four times compared with the mice treated with virus alone. However, the mice
      later developed chronic BA with persistent low body weight and jaundice. Hepatic
      inflammatory cells were reduced compared with acute BA. Blockade of extrahepatic
      bile ducts occurred, whereas intrahepatic ductules were partially preserved, and
      a progressive increase in liver fibrosis was observed. High levels of CD11b+Gr-1+
      cells were present in these mice. The administration of an anti-Ly6G antibody
      again in those chronic BA mice reduced jaundice and restored body weight. In BA
      patients CD177+ cells were highly expressed in the liver. Our data suggest that
      the chronic mouse BA model shares key characteristics with clinical BA and
      indicates the importance of CD11b+Gr-1+ cells in the initiation and progression
      of BA.

PMID- 30201499
TI  - Genetic analysis in a cohort of patients with hereditary optic neuropathies in
      Southwest of China.
AB  - We report the results of molecular screening in 121 patients with suspected
      hereditary optic neuropathies. The 34 primary and 9 secondary LHON mutations were
      screened in all the patients. In the familial cases, OPA1 was also tested when
      negative finding for the mtDNA mutations screening. Molecular defects were
      identified in 35 patients (28.9% of screened patients). Among these, 33 patients
      (94.3%) had an mtDNA mutation, including m.11778G > A (69.7%), m.14484 T > C,
      m.3460G > A, m.3635G > A, m.14502 T > C and three secondary mutations m.3316G >
      A, m.3394 T > C, m.3497C > T. Two novel OPA1 mutations, c.1301 T > G
      (p.Leu434Arg) and c.985-1G > A (IVS9-1G > A), were also detected in families with
      the evidence of father-to-son transmission. In conclusion, we reported the
      results of the molecular screening of 121 patients with hereditary optic
      neuropathies from southwest of China. Our results highlight the importance of
      investigating LHON-causing mtDNA mutations and OPA1 mutations in cases of
      suspected hereditary optic neuropathy.

PMID- 30201500
TI  - Recent trends in molecular epidemiology of Hepatitis C virus in Mardan, KPK
      Pakistan.
AB  - To determine the genotypic distribution of HCV, frequency of risk factors
      involved in its transmission, and correlation of genotype with viral load in
      Mardan population which is the second largest city of Khyber Pakhtunkhwa (KPK),
      Pakistan. Blood samples of 1140 were collected from different regions of Mardan
      and major proportion of recruited patients were internally displaced people
      (IDPs), refugees, and slum dwellers. Complete patient's history was analyzed to
      assess the possible risks involved in HCV transmission. Viral genotype was
      determined by PCR (polymerase chain reaction) whereas, HCV RNA was measured by
      qRT-PCR. Data was analyzed using SPSS statistical software. Our results indicate
      3a as the most abundant subtype in Mardan population followed by 3b, 2a, 2b, 4a,
      untypeable, mixed, 1a, and 1b. In contrast to previous findings, genotype 1 was
      the least prevalent genotype and the overall prevalence of HCV in Mardan
      population was significantly higher in females (n = 687, 60.2%) than males (n =
      453, 39.7%). Significant difference between-genotypes and gender was observed in
      genotype 1 (p < .034) and genotype 3 (p < .004). The mean age was 44 (SD +/-
      9.51). The most frequently found mixed genotype was 3a + 1b and mixed genotype
      was more prevalent in males. The proportion of middle-aged people (41-49 years)
      was higher whereas, older and younger people were least infected with HCV. This
      is the first study that showed substantial correlation of genotype 3 with low and
      intermediate viral load in Mardan population. Moreover, high and extremely high
      viral load was associated with other genotypes. Our findings showed that most of
      the patients who experienced high and extremely high viremia in their blood were
      males and belonged to Takhat Bhai and Mardaan regions. There were significant
      difference in the prevalence of HCV genotype 3a (p = .001) and genotype 3b (p =
      .005) in different regions of Mardan. Pre-treatment viral load is significantly
      high (p 0.001) in tehsil Mardan patients infected with HCV genotype 3 as compared
      to other genotypes. Unsafe medical practices such as medical and dental
      surgeries, intravenous drug use, and blood transfusions were the main risk
      factors for HCV transmission in Mardan, KPK Pakistan. This study gives clear
      insights into the epidemiological status of HCV in Mardan population. Genotype 3
      is correlated with low and intermediate viral load whereas high viral loads were
      revealed among patients infected with genotypes other than genotype 3. In the
      absence of better data and robust epidemiological information, this detailed
      analysis of HCV genotypes with special reference to risk factors, pretreatment
      viral load, gender, and age will provide the baseline data for development of
      optimal HCV eradication and preventive strategies.

PMID- 30201502
TI  - Biomimetic cardiovascular platforms for in vitro disease modeling and therapeutic
      validation.
AB  - Bioengineered tissues have become increasingly more sophisticated owing to recent
      advancements in the fields of biomaterials, microfabrication, microfluidics,
      genetic engineering, and stem cell and developmental biology. In the coming
      years, the ability to engineer artificial constructs that accurately mimic the
      compositional, architectural, and functional properties of human tissues, will
      profoundly impact the therapeutic and diagnostic aspects of the healthcare
      industry. In this regard, bioengineered cardiac tissues are of particular
      importance due to the extremely limited ability of the myocardium to self
      regenerate, as well as the remarkably high mortality associated with
      cardiovascular diseases worldwide. As novel microphysiological systems make the
      transition from bench to bedside, their implementation in high throughput drug
      screening, personalized diagnostics, disease modeling, and targeted therapy
      validation will bring forth a paradigm shift in the clinical management of
      cardiovascular diseases. Here, we will review the current state of the art in
      experimental in vitro platforms for next generation diagnostics and therapy
      validation. We will describe recent advancements in the development of smart
      biomaterials, biofabrication techniques, and stem cell engineering, aimed at
      recapitulating cardiovascular function at the tissue- and organ levels. In
      addition, integrative and multidisciplinary approaches to engineer biomimetic
      cardiovascular constructs with unprecedented human and clinical relevance will be
      discussed. We will comment on the implementation of these platforms in high
      throughput drug screening, in vitro disease modeling and therapy validation.
      Lastly, future perspectives will be provided on how these biomimetic platforms
      will aid in the transition towards patient centered diagnostics, and the
      development of personalized targeted therapeutics.

PMID- 30201501
TI  - High prevalence of cyclovirus Vietnam (CyCV-VN) in plasma samples from Madagascan
      healthy blood donors.
AB  - Cycloviruses, small ssDNA viruses belonging to the Circoviridae family, have been
      suggested as possible causes of enteric, respiratory and neurological disorders
      in human patients. One of these species, cyclovirus-Vietnam (CyCV-VN), initially
      isolated from cerebrospinal fluid samples of patients with unexplained
      neurological disorders, has since been reported in serum samples from chronically
      patients infected with HBV, HCV or HIV, in Italy. On the other hand, CyCV-VN was
      not detected in serum samples from healthy individuals. Here, we report on a high
      prevalence of 43.4% (40/92) of CyCV-VN in plasma samples from asymptomatic blood
      donors from Madagascar. Interestingly, this virus was not detected by
      metagenomics and PCR in six other African countries, suggesting regional
      differences in CyCV-VN prevalence across Africa. Phylogenetic analysis based on
      the complete genomes showed that CyCV-VN sequences isolated from blood were most
      closely related to sequences previously reported from human stool in Madagascar.
      Further investigations using larger cohorts are required to determine the global
      epidemiology, the natural history and the pathological significance, if any, of
      CyCV-VN infection in humans.

PMID- 30201503
TI  - Usefulness of environmental DNA for detecting Schistosoma mansoni occurrence
      sites in Madagascar.
AB  - OBJECTIVES: Schistosomiasis is an important disease in Madagascar, and several
      studies on the disease have focused on the occurrence of the parasite in humans.
      However, the range of the pathogen in the environment and its impact on human
      infection is difficult to predict. An environmental DNA (eDNA) detection system
      for Schistosoma mansoni was developed to improve schistosomiasis eco-epidemiology
      studies. METHODS: Primers and probes were designed and tested in experimental
      biotopes. The field study was conducted in Maevatanana District of Madagascar.
      Seven water sources with human use were sampled, with a total of 21 water samples
      collected. Snails were collected, and patients were examined by ultrasound to
      determine the occurrence of schistosomiasis in the study area. RESULTS: One water
      source with active transmission was identified through the detection of S.
      mansoni eDNA in the water and the intermediate host Biomphalaria pfeifferi
      collected from the same water source. People with clinical schistosomiasis were
      found in the area, reinforcing the findings. CONCLUSIONS: The application of eDNA
      in eco-epidemiology enables the determination of hot spots and safe spots in
      endemic areas, constituting an alternative ecological tool for follow-up and
      monitoring of control programs for schistosomiasis, and contributing information
      on water safety for improving the standard of living of the people in endemic
      areas.

PMID- 30201504
TI  - Measles outbreak in a French Roma community in the Provence-Alpes-Cote d'Azur
      region, France, May to July 2017.
AB  - OBJECTIVES: To analyse a measles outbreak in a Roma community. METHODS: We
      describe a community-wide outbreak of genotype D8 measles that took place in
      southeastern France, between May and July 2017, along with the control measures
      adopted. RESULTS: We identified a total of eighteen cases, between six months and
      24 years old. All cases were unvaccinated or incompletely vaccinated and belonged
      to a sedentary French Roma community. Most of them (67%) were hospitalised, with
      three cases (17%) of severe measles including one death of a 16-year-old girl who
      had previously received oral corticosteroids. The latter was the only lethal case
      notified in France during the year 2017. Control measures included
      intensification of surveillance, isolation of cases, and a large vaccination
      campaign in this Roma community. During the outbreak period, there was no case of
      healthcare-associated measles transmission. A broad adherence to vaccination
      through the mediating role of both the chief of the community and the pastor
      allowed reaching completed vaccination coverage of 90%. CONCLUSIONS: Efforts
      should be concentrated to enhance access to health services for minorities such
      as the Roma community characterized by low vaccination coverage. A trustful
      relationship with leaders of the community is essential to ensure adherence to
      vaccination. In France, attributable mortality to measles is low and concerns
      mainly unvaccinated and immunodepressed patients.

PMID- 30201505
TI  - First description of agonist and antagonist IP-10 in urine of patients with
      active TB.
AB  - OBJECTIVES: Biomarkers for tuberculosis (TB) diagnosis and clinical management
      are needed to defeat TB. In chronic hepatitis, patients not responding to
      interferon/ribavirin treatment had high levels of an antagonist form of IP-10.
      Recently, antagonist IP-10 has been shown to be involved also in TB pathogenesis.
      Here, we investigated IP-10 agonist/antagonist forms as potential inflammatory
      biomarkers to support TB diagnosis and monitoring. METHODS: Total IP-10 and its
      agonist/antagonist forms were measured by SIMOA digital ELISA in urine obtained
      from patients with active TB at baseline and after treatment. Healthy donors (HD)
      and patients with pneumonia were enrolled as controls. RESULTS: Patients with
      active TB had significantly higher levels of total and agonist IP-10 at baseline
      compared to HD; conversely, no differences were observed between IP-10 levels in
      active TB vs pneumonia. Moreover, in active TB a decline of total urine IP-10 was
      observed at therapy completion; agonist/antagonist forms reflected this decline
      although their differences were not statistically significant. CONCLUSIONS: We
      showed for the first time that agonist/antagonist IP-10 forms are measurable in
      urine. IP-10 levels associate with TB and pneumonia disease, suggesting their
      association with acute inflammation. Further studies are needed to assess their
      role to monitor TB treatment efficacy.

PMID- 30201506
TI  - Dissemination of localized Mycobacterium malmoense infection in an
      immunocompromised patient.
AB  - A 75-year-old woman with a history of immunosuppressive treatment for rheumatoid
      arthritis and non-Hodgkin lymphoma, was referred to our reference centre for
      treatment of tenosynovitis caused by Mycobacterium malmoense, which had
      disseminated due to immunosuppressive therapy. This rare diagnosis was made after
      years of treatment for supposed rheumatoid arthritis. The patient presented with
      relapsing tenosynovitis with wounds on her right middle finger and wounds on her
      left lower leg, despite 3 months of adequate therapy
      (rifampicin+ethambutol+clarithromycin). Therapy was intensified with amikacin,
      clofazimine, moxifloxacin, and interferon-gamma due to the lack of response.
      Amputation of the right middle finger was necessary due to advanced disease.
      Treatment was further complicated by a paradoxical reaction, requiring prednisone
      treatment, which ultimately led to cure.

PMID- 30201507
TI  - Vaccine-associated paralytic poliomyelitis in the Russian Federation in 1998
      2014.
AB  - OBJECTIVES: Different polio vaccination schemes have been used in Russia: oral
      polio vaccine (OPV) was used in 1998-2007 and inactivated polio vaccine (IPV)
      followed by OPV in 2008-2014. This article presents the characteristics of
      vaccine-associated paralytic poliomyelitis (VAPP) cases in Russia during this
      period. METHODS: VAPP cases were identified through the acute flaccid paralysis
      surveillance system, classified by the National Expert Classification Committee.
      Criteria for a 'recipient VAPP' (rVAPP) case were poliomyelitis symptoms 6-30days
      after OPV administration, isolation of the vaccine virus, and residual paralysis
      60days after disease onset. Unvaccinated cases with a similar picture 6-60days
      after contact with an OPV recipient were classified as 'contact VAPP' (cVAPP)
      cases. RESULTS: During 1998-2014, 127 VAPP cases were registered: 82 rVAPP and 45
      cVAPP. During the period in which only OPV was used, rVAPP cases prevailed
      (73.8%); cases of rVAPP were reduced during the sequential scheme period (15%).
      Poliovirus type 3 (39.5%) and type 2 (23.7%) were isolated more often. Vaccine
      derived poliovirus types 1, 2, and 3 were isolated from three cases of cVAPP. The
      incidence of VAPP cases was higher during the period of OPV use (1 case/1.59
      million OPV doses) than during the sequential scheme period (1 case/4.18 million
      doses). CONCLUSION: The risk of VAPP exists if OPV remains in the vaccination
      schedule.

PMID- 30201508
TI  - Sexual transmission of arboviruses: More to explore?

PMID- 30201509
TI  - Pulmonary Campylobacter concisus infection in an immunocompromised patient with
      underlying mucormycosis.
AB  - Campylobacter concisus is a rarely encountered agent of human infection. The
      first isolation of C. concisus from a pulmonary abscess in an immunocompromised
      patient who underwent allogeneic stem cell transplantation is reported here. This
      unusual case demonstrates the pathogenic potential of this bacterium and outlines
      species-immanent difficulties in gaining a reliable diagnosis. Molecular methods
      were a cornerstone for definite identification of the organism grown on anaerobic
      culture from surgically excised tissue. Antimicrobial susceptibility testing
      revealed unusual quinolone and macrolide resistance, and therefore antimicrobial
      therapy was based on beta-lactam antibiotics.

PMID- 30201510
TI  - A Joint Statement from the European Association of Urology Renal Cell Cancer
      Guidelines Panel and the International Kidney Cancer Coalition: The Rejection of
      Ipilimumab and Nivolumab for Renal Cancer by the Committee for Medicinal Products
      for Human Use Does not Change Evidence-based Guideline Recommendations.

PMID- 30201511
TI  - Can Ebola Virus Vaccines Have Universal Immune Correlates of protection?
AB  - Testing vaccine efficacy against the highly lethal Ebola virus (EBOV) in humans
      is almost impossible due to obvious ethical reasons and the sporadic nature of
      outbreaks. For such situations, the 'animal rule' was established, requiring the
      product be tested in animal models, expected to predict the response observed in
      humans. For vaccines, this testing aims to identify immune correlates of
      protection, such as antibody or cell-mediated responses. In the wake of the 2013
      2016 EBOV epidemic, and despite advancement of promising candidates into clinical
      trials, protective correlates remain ambiguous. In the hope of identifying a
      reliable correlate by comparing preclinical and clinical trial data on immune
      responses to vaccination, we conclude that correlates are not universal for all
      EBOV vaccines.

PMID- 30201512
TI  - A Balancing Act: MDA5 in Antiviral Immunity and Autoinflammation.
AB  - Induction of interferons during viral infection is mediated by cellular proteins
      that recognise viral nucleic acids. MDA5 is one such sensor of virus presence and
      is activated by RNA. MDA5 is required for immunity against several classes of
      viruses, including picornaviruses. Recent work showed that mutations in the IFIH1
      gene, encoding MDA5, lead to interferon-driven autoinflammatory diseases.
      Together with observations made in cancer cells, this suggests that MDA5 detects
      cellular RNAs in addition to viral RNAs. It is therefore important to understand
      the properties of the RNAs which activate MDA5. New data indicate that RNA length
      and secondary structure are features sensed by MDA5. We review these developments
      and discuss how MDA5 strikes a balance between antiviral immunity and
      autoinflammation.

PMID- 30201513
TI  - Corrigendum to "The role of protein methyltransferases as potential novel
      therapeutic targets in squamous cell carcinoma of the head and neck" [Oral Oncol.
      81 (2018) 100-108].

PMID- 30201515
TI  - The IgE memory reservoir in food allergy.

PMID- 30201516
TI  - Rational design and development of a stable liquid formulation of riluzole and
      its pharmacokinetic evaluation after oral and IV administrations in rats.
AB  - Enterally administered riluzole is currently being investigated in a Phase II/III
      clinical trial for the treatment of acute spinal cord injury (SCI). Many SCI
      patients suffer from severe motor dysfunction and exhibit swallowing difficulties
      and cannot swallow riluzole tablets. The purpose of the present study was to
      develop a liquid solution formulation of riluzole, which can be administered more
      easily to this patient population with the capability to adjust the dose if
      needed. Riluzole was solubilized using water miscible organic solvents, namely,
      polyethylene glycol 400, propylene glycol and glycerin. A Central Composite
      Design (CCD) approach was used to develop an optimum co-solvent composition that
      can solubilize the entire 50 mg dose of riluzole in 5 ml. A three-factor five
      level design was employed to investigate the effects of composition of co
      solvents on riluzole solubility. The selected optimum formulation consists of 15%
      v/v PEG 400, 20% v/v propylene glycol and 10% v/v glycerin, with riluzole
      concentration of 10 mg/ml. The optimum composition was assessed for stability at
      different temperatures. Satisfactory stability was obtained at room temperature
      and 4  degrees C (t90 of 17 and 35 months, respectively). The optimum formulation
      of riluzole was suitable for both oral and intravenous administrations. Single
      dose pharmacokinetic studies of the optimum formulation by oral and IV routes
      were evaluated in rats, using commercially available Rilutek(r) tablets as a
      reference. The co-solvent formulation was well tolerated both orally and
      intravenously. In comparison to the commercial tablet, the co-solvent formulation
      had a faster rate of absorption and more sustained plasma levels with a
      significantly longer elimination half-life. Higher concentrations of riluzole in
      brain and spinal cord were achieved from co-solvent formulation as compared to
      tablet. The riluzole solution formulation is stable and offers advantages of ease
      of administration, consistent dosing, rapid onset and longer duration of action,
      better availability at site of action which can be extremely beneficial for the
      therapy in SCI patients.

PMID- 30201514
TI  - An admixture mapping meta-analysis implicates genetic variation at 18q21 with
      asthma susceptibility in Latinos.
AB  - BACKGROUND: Asthma is a common but complex disease with racial/ethnic differences
      in prevalence, morbidity, and response to therapies. OBJECTIVE: We sought to
      perform an analysis of genetic ancestry to identify new loci that contribute to
      asthma susceptibility. METHODS: We leveraged the mixed ancestry of 3902 Latinos
      and performed an admixture mapping meta-analysis for asthma susceptibility. We
      replicated associations in an independent study of 3774 Latinos, performed
      targeted sequencing for fine mapping, and tested for disease correlations with
      gene expression in the whole blood of more than 500 subjects from 3 racial/ethnic
      groups. RESULTS: We identified a genome-wide significant admixture mapping peak
      at 18q21 in Latinos (P = 6.8 * 10-6), where Native American ancestry was
      associated with increased risk of asthma (odds ratio [OR], 1.20; 95% CI, 1.07
      1.34; P = .002) and European ancestry was associated with protection (OR, 0.86;
      95% CI, 0.77-0.96; P = .008). Our findings were replicated in an independent
      childhood asthma study in Latinos (P = 5.3 * 10-3, combined P = 2.6 * 10-7). Fine
      mapping of 18q21 in 1978 Latinos identified a significant association with
      multiple variants 5' of SMAD family member 2 (SMAD2) in Mexicans, whereas a
      single rare variant in the same window was the top association in Puerto Ricans.
      Low versus high SMAD2 blood expression was correlated with case status (13.4%
      lower expression; OR, 3.93; 95% CI, 2.12-7.28; P < .001). In addition, lower
      expression of SMAD2 was associated with more frequent exacerbations among Puerto
      Ricans with asthma. CONCLUSION: Ancestry at 18q21 was significantly associated
      with asthma in Latinos and implicated multiple ancestry-informative noncoding
      variants upstream of SMAD2 with asthma susceptibility. Furthermore, decreased
      SMAD2 expression in blood was strongly associated with increased asthma risk and
      increased exacerbations.

PMID- 30201517
TI  - Unmet Need and Financial Impact Disparities for US Children with ADHD.
AB  - OBJECTIVE: The 5.1 million US children with attention-deficit/hyperactivity
      disorder (ADHD) have pronounced needs in education, occupational and speech
      therapy, and medical and behavioral treatments. Given known associations of ADHD
      diagnosis with race/ethnicity and parent education, this study aimed to assess
      how measures of socioeconomic status correlate with both adverse family financial
      impact of ADHD and disparities in unmet treatment need for ADHD. METHODS:
      Secondary analysis of children ages 8 to 17 years whose households participated
      in the 2014 National Survey of the Diagnosis and Treatment of Attention
      Deficit/Hyperactivity Disorder and Tourette Syndrome. Using bivariate testing, we
      examined associations among measures of socioeconomic status with unmet ADHD
      treatment need and family financial impact. Logistic regression models estimated
      the odds of having unmet treatment need, adjusting for demographic factors and
      family financial impact. RESULTS: Among US school-aged children with a current
      ADHD diagnosis, 44.3% experienced an adverse family financial impact from ADHD,
      and 11.6% had unmet need for ADHD treatment. Children with younger age at first
      ADHD diagnosis were more likely to experience adverse family financial impact.
      Children from non-English-speaking households were less likely to report unmet
      need compared to those from primarily English-speaking households. The adjusted
      odds of unmet need were twice as great among those who reported adverse family
      financial impact. CONCLUSION: Deeper understanding of the influence of the
      household language is important in ADHD needs assessments. Considering overall
      family financial circumstances may also be pertinent, particularly as children
      age, because earlier diagnosis was associated with adverse financial outcomes.
      These findings could shape future clinic policies for targeting community
      resources.

PMID- 30201518
TI  - Operation Homefront: Meeting Clerkship Competencies with Home Visits to Families
      of Children with Special Needs.
AB  - OBJECTIVE: We assessed how third-year medical students' written reflections on
      home visit experiences with families of children with special needs demonstrate
      evidence of exposure to 9 selected competencies for pediatric clerkships
      designated by the Council on Medical Student Education in Pediatrics. METHODS: We
      reviewed written reflections from 152 third-year medical students. For each
      competency (2 related to communication were combined), we tabulated the number of
      reflections in which a given competency was demonstrated. Within each competency,
      themes are described and presented with exemplary quotes to provide a more robust
      picture of students' exposure and experience. RESULTS: Of 152 reflections, 100%
      demonstrated at least 1 of the 8 expected competencies. Each reflection exhibited
      an average of 3 (3.1) competencies (range: 1-7). The competencies most frequently
      mentioned were demonstration of respect for patient, parent, and family
      attitudes, behaviors, and lifestyles (90%) and demonstration of positive attitude
      toward education (76%). Less frequently mentioned competencies included
      demonstration of behaviors and attitudes that promote patients' and families'
      best interests (41%), demonstration of effective verbal and nonverbal
      communication skills (a combination of 2 communication-related competencies)
      (33%), and description of barriers that prevent children from accessing health
      care (37%). The following competencies were least often mentioned: description of
      a pediatrician's role and responsibility in advocating for patients' needs (10%),
      description of the important role of patient education (8%), or description of
      the types of problems that benefit from a community approach (17%). CONCLUSIONS:
      Our analysis demonstrates that community-based home visits can provide medical
      students with opportunities to meet required pediatric clerkship competencies.

PMID- 30201520
TI  - Manifestations of socioeconomic status and its association with physical child
      punishment- Results from the Multi-Indicators Cluster Survey in Viet Nam, 2006
      2014.
AB  - Physical child punishment is a critical public health problem that exhibits
      negative and long-lasting mental and physical health consequences. Yet, the
      predictors of physical punishment are understudied in developing countries, and
      disparities that exist between levels of economic status are not known well. The
      socioeconomic predictors of physical child punishment were investigated using
      three rounds of the Multiple Indicator Cluster Survey (MICS) results in a lower
      middle-income country, Viet Nam from 2006 to 2014. A total of 16,784 households
      that have answered the child punishment questionnaire from MICS data from 2006 to
      2014 were included in the analysis. Descriptive statistics, univariate, and
      multivariate logistic regression analyses were conducted. A secular trend of
      disparity was investigated with and without the parents' normative values on
      physical punishment. Children in Viet Nam have been subject to some form of
      violent physical punishment by their parents or caregivers. About half of the
      children in the poorest households (44.7%) experienced physical child punishment
      while lesser percentage of children in the richer households experienced physical
      child punishment. Disparities existed across different wealth groups as the
      prevalence of physical child punishment decreased: the gap between the poorest
      and the richest group widened. Compared to the richest households, the poorest
      households were more likely to experience physical child punishment AOR 1.58 (95%
      CI 1.39-1.79). There is a decrease in the prevalence of physical punishment over
      the recent years in Viet Nam, socioeconomic disparities, in contrast, have
      increased, and the poorest children have a higher risk of experiencing physical
      child punishment. Such disparities should be considered in future research and
      intervention development.

PMID- 30201519
TI  - NOD and NOR mice exhibit comparable development of lacrimal gland secretory
      dysfunction but NOD mice have more severe autoimmune dacryoadenitis.
AB  - The male Non-Obese Diabetic (NOD) mouse is an established model of autoimmune
      dacryoadenitis characteristic of Sjogren's Syndrome (SS), but development of
      diabetes may complicate studies. The Non-Obese Diabetes Resistant (NOR) mouse is
      a MHC-II matched diabetes-resistant alternative, but development of autoimmune
      dacryoadenitis is not well-characterized. We compare features of SS in male NOD
      and NOR mice at 12 and 20 weeks. Stimulated tear secretion was decreased in 12
      week NOD relative to BALB/c mice (p < 0.05), while by 20 weeks both NOD and NOR
      showed decreased stimulated tear secretion relative to BALB/c mice (p < 0.001).
      Tear CTSS activity was elevated in NOD and NOR relative to BALB/c mice (p < 0.05)
      at 12 and 20 weeks. While NOD and NOR lacrimal glands (LG) showed increased LG
      lymphocytic infiltration at 12 and 20 weeks relative to BALB/c mouse LG (p <
      0.05), the percentage in NOD was higher relative to NOR at each age (p < 0.05).
      Gene expression of CTSS, MHC II and IFN-gamma in LG were significantly increased
      in NOD but not NOR relative to BALB/c at 12 and 20 weeks. Redistribution of the
      secretory effector, Rab3D in acinar cells was observed at both time points in NOD
      and NOR, but thinning of myoepithelial cells at 12 weeks in NOD and NOR mice was
      restored by 20 weeks in NOR mice. NOD and NOR mice share features of SS-like
      autoimmune dacryoadenitis, suggesting common disease etiology. Other findings
      suggest more pronounced lymphocytic infiltration in NOD mouse LG including
      increased pro-inflammatory factors that may be unique to this model.

PMID- 30201521
TI  - Economics and violence against children, findings from the Violence Against
      Children Survey in Nigeria.
AB  - This study seeks to assess the impact of economic factors on sexual, emotional,
      and physical violence on Nigerian children and adolescents aged 13-24 years. Data
      collected from the Nigerian Violence Against Children Survey (VACS), a national,
      cross-sectional household survey of females and males aged 13-24 years were used
      to examine sexual, emotional, and physical violence victimization. Data were
      collected on household economic status, e.g., flooring and roofing materials,
      transportation. A poverty index was developed using the Simple Poverty
      ScorecardTM for Nigeria to determine the impact that economic factors have on
      these violence measures. Children aged 13-17 years in households with high
      economic status (ES) were 1.81, 1.78, and 4.91 times, more likely to experience
      sexual, emotional, and physical violence, respectively, within the last 12 months
      than those in the lowest ES. Individuals aged 18-24 years in households with high
      ES were 1.62 and 1.41 times more likely to experience emotional and physical
      violence, respectively, prior to age 18 than those in the lowest ES. Individuals
      aged 18-24 years in households with middle or high ES were 1.65 and 1.96,
      respectively, times more likely to experience physical violence prior to age 18
      than those in the lowest ES. Highest tertile ES was significantly associated with
      sexual, emotional, and physical violence among Nigerians aged 13-24 years.
      Further research is needed to determine the cause of increased violence amongst
      high ES households. Targeted interventions towards this ES class are recommended
      to reduce violence against children in Nigeria.

PMID- 30201522
TI  - Antibody-cytokine fusion proteins: Biopharmaceuticals with immunomodulatory
      properties for cancer therapy.
AB  - Cytokines have long been used for therapeutic applications in cancer patients.
      Substantial side effects and unfavorable pharmacokinetics limit their application
      and may prevent dose escalation to therapeutically active regimens. Antibody
      cytokine fusion proteins (often referred to as immunocytokines) may help localize
      immunomodulatory cytokine payloads to the tumor, thereby activating anticancer
      immune responses. A variety of formats (e.g., intact IgGs or antibody fragments),
      molecular targets (e.g., extracellular matrix components and cell membrane
      antigens) and cytokine payloads have been considered for the development of this
      novel class of biopharmaceuticals. This review presents the basic concepts on the
      design and engineering of immunocytokines, reviews their potential limitations,
      points out emerging opportunities and summarizes key features of preclinical and
      clinical-stage products.

PMID- 30201523
TI  - Development of an in vitro model to study hepatitis C virus effects on
      hepatocellular lipotoxicity and lipid metabolism.
AB  - Hepatic steatosis is common in patients infected with hepatitis C virus (HCV).
      Particularly in patients infected with non-genotype 3 HCV, hepatic steatosis is
      closely related to factors of the metabolic syndrome such as hyperlipidemia.
      However, the molecular mechanisms involved in this "metabolic" steatosis in non-3
      genotype HCV infections are not well understood. Here, we aimed to develop an in
      vitro model to study the effect of genotype 1 HCV infection on hepatic
      lipotoxicity and lipid metabolism. Cellular lipid accumulation was induced in Huh
      7 hepatoma cells transfected with HCV genotype 1b replicon (HCV+) by incubation
      with increasing doses of palmitic acid (C16:0) or oleic acid (C18:1 n-9)
      complexed to albumin mimicking hyperlipidemic conditions. Mock transfected
      hepatoma cells (HCV-) were used as controls. Incubation with oleic acid
      concentrations as high as 0.5 mM did not induce toxic effects in HCV+ or HCV-
      cells. In contrast, incubation with palmitic acid caused dose-dependently
      cytotoxic effects which were more pronounced in HCV+ compared to HCV- cells.
      Further analysis with subtoxic palmitic and oleic acid concentrations revealed a
      higher uptake of fatty acids and intracellular triglyceride accumulation in HCV+
      compared to HCV- cells. Carnitine palmitoyltransferase I (CPT1) expression,
      indicative of mitochondrial beta-oxidation, was markedly stimulated by lipid
      exposure in HCV+ but not in HCV- cells. Furthermore, heme oxygenase 1 (HMOX1)
      expression levels increased in FA stimulated cells, and this increase was
      significantly higher in HCV+ compared to HCV- cells. In contrast, expression of
      the key enzymes of hepatic de novo lipogenesis fatty acid synthase (FASN) and
      stearoyl-CoA desaturase (SCD-1) was significantly reduced upon oleate exposure in
      HCV- but not in HCV+ cells. In summary, our newly developed cell culture model
      revealed effects of HCV genotype 1b infection on metabolic susceptibility to
      lipid accumulation and toxicity particularly to saturated lipids. These results
      may indicate that HCV (genotype 1b) infected individuals with hyperlipidemia may
      benefit from dietary or pharmacological intervention.

PMID- 30201524
TI  - Post-Mortem Evaluation of Potentially Survivable Hemorrhagic Death in a Civilian
      Population.
AB  - BACKGROUND: Although the survivability of military extremity hemorrhage is well
      documented, equivalent civilian data are limited. We analyzed statewide autopsy
      records in Maryland to determine the number of hemorrhagic deaths that might have
      been potentially survivable with prompt hemorrhage control. Similar analyses of
      battlefield deaths led to life-saving changes in military medical practice. STUDY
      DESIGN: This is a retrospective study of decedent records. The objective is to
      estimate the number of hemorrhagic deaths that might have been prevented by
      prompt placement of an extremity tourniquet. Maryland autopsy records from 2002
      to 2016 were selected using the following search terms: amputation, arm/arms,
      avulsion, exsanguination, extremity/extremities, leg/legs. The records were
      analyzed by applying a checklist of previously developed military criteria to
      characterize deaths as potentially survivable or nonsurvivable with prompt use of
      a tourniquet. Suicides and decedents less than 18 years old were excluded. The
      study did not use information about living participants. Two expert reviewers
      independently evaluated and scored the death records. Deaths were classified as
      either potentially survivable or nonsurvivable. A third reviewer broke any ties.
      RESULTS: There were 288 full autopsy records included in the final analysis. Of
      the eligible decedents reviewed during the 14-year period, 124 of 288 had
      potentially survivable wounds; 164 had nonsurvivable wounds. CONCLUSIONS: Over
      the 14-year study interval, 124 Maryland decedents-an average of 9 per year-might
      have been saved with prompt placement of a tourniquet. If extrapolated,
      approximately 480 people in the US might be saved per year. These results provide
      evidence to support educating and equipping the public to provide bleeding
      control.

PMID- 30201525
TI  - 4-(3-Alkyl-2-oxoimidazolidin-1-yl)-N-phenylbenzenesulfonamides as new antimitotic
      prodrugs activated by cytochrome P450 1A1 in breast cancer cells.
AB  - The role and the importance of the sulfonate moiety in phenyl 4-(2-oxo-3
      alkylimidazolidin-1-yl)benzenesulfonates (PAIB-SOs) were assessed using its
      bioisosteric sulfonamide equivalent leading to new cytochrome P450 1A1 (CYP1A1)
      activated prodrugs designated as 4-(3-alkyl-2-oxoimidazolidin-1-yl)-N
      phenylbenzenesulfonamides (PAIB-SAs). PAIB-SAs are active in the submicromolar to
      low micromolar range showing selectivity toward CYP1A1-expressing MCF7 cells as
      compared to cells devoid of CYP1A1 activity such as MDA-MB-231 and HaCaT cells.
      The most potent, PAIB-SA 13, bearing a trimethoxyphenyl group on ring B blocks
      the cell cycle progression in G2/M phase, disrupts the microtubule dynamics and
      is biotransformed by CYP1A1 into CEU-638, its potent antimicrotuble counterpart.
      Structure-activity relationships related to PAIB-SOs and PAIB-SAs evidenced that
      PAIB-SOs and PAIB-SAs are true bioisosteric equivalents fully and selectively
      activatable by CYP1A-expressing cells into potent antimitotics.

PMID- 30201526
TI  - Mechanisms and characteristics of biofilm formation via novel DEAMOX system based
      on sequencing biofilm batch reactor.
AB  - A denitrifying ammonium oxidation (DEAMOX) process has been regarded as an
      innovative process to simultaneously treat ammonia and nitrate containing
      wastewaters, whereas very limited research has focused on its application in
      biofilm system. In this research, a novel DEAMOX process was established with
      fixed sponge carriers in a sequencing biofilm batch reactor (SBBR). To
      investigate biofilm formation process and characteristics can encourage further
      research on DEAMOX system optimization, deteriorated performance recovery
      strategies and application with actual wastewater. Total nitrogen removal
      efficiency was maintained at 93.0 % after 240 days of operation. With biofilm
      growth, the protein-like extracellular polymeric substances (EPS) and tightly
      bound EPS (TB-EPS) of biofilms increased from 65.6 to 46.1, to 179.6 and 142.0 mg
      gVSS-1, respectively, revealing that protein-like substances and TB-EPS promote
      biofilm formation. The mechanism of biofilm formation was discussed by analyzing
      the morphological development and functional bacterial activities of biofilms.
      Furthermore, high anammox activity was obtained in biofilms with specific NH4+N
      removal rates over 4.29 mgN gVSS-1h-1, which were significantly higher than in
      suspended sludge (2.56 mgN gVSS-1h-1). Quantitative polymerase chain reaction
      results showed that the abundance of anammox bacteria in biofilms increased from
      1.87 % to 11.48 % with biofilm growth. These results imply that mature biofilms
      formed on carriers and the anammox bacteria were sufficient enriched in DEAMOX
      SBBR system.

PMID- 30201527
TI  - Densitometric quantification for the validation of decolorization of Disperse
      Orange ERL by lichen Parmelia sp.
AB  - Densitometric HPTLC quantification method was developed to validate the
      decolorization/biotransformation of Disperse Orange ERL and dye mixture by lichen
      Parmelia sp. which release several colored compounds during decolorization
      process, hence unable to use colorimetric estimation. Percent decolorization of
      Disperse Orange ERL and dye mixture by lichen Parmelia sp. was observed when
      estimated using developed high performance thin layer chromatography method.
      Limit of detection and limit of quantification for both dyes in mixture were
      obtained as 0.3 and 1 MUg/MUl, respectively. Area of peak of control Disperse
      Orange ERL was reduced by 43% after 12 h, 71% after 48 h and upto 82% after 72 h
      of incubation. Precision and repeatability of data elucidated the % relative
      standard deviation less than 3 for all the values thus indicating statistically
      acceptable. Biodegradation of dye and mixture was confirmed with FTIR analysis,
      i.e., altered fingerprinting spectral pattern.

PMID- 30201528
TI  - Phylogeny and physiology of candidate phylum BRC1 inferred from the first
      complete metagenome-assembled genome obtained from deep subsurface aquifer.
AB  - Candidate bacterial phylum BRC1 has been identified in a broad range of mostly
      organic-rich oxic and anoxic environments through molecular analysis of microbial
      communities. None of the members of BRC1 have been cultivated and only a few
      draft genome sequences have been obtained from metagenomes or as a result of
      single-cell sequencing. We have reconstructed complete genome of BRC1 bacterium,
      BY40, from metagenome of the microbial community of a deep subsurface thermal
      aquifer in the Tomsk Region of the Western Siberia, Russia, and used it for
      metabolic reconstruction and comparison with existing genomic data. Analysis of
      3.3Mb genome of BY40 bacterium revealed numerous glycoside hydrolases that could
      enable utilization of carbohydrates, including enzymes of chitin-degradation
      pathway. The bacterium lacks flagellar machinery but the twitching motility is
      encoded. The reconstructed central metabolism revealed pathways enabling the
      fermentation of organic substrates, as well as their complete oxidation through
      aerobic and anaerobic respiration. Phylogenetic analysis using BY40 genome
      supported the phylum level classification of BRC1 lineage. Based on phylogenetic
      and genomic analyses, the novel bacterium is proposed to be classified as
      Candidatus Sumerlaea chitinivorans, within a candidate phylum Sumerlaeota.

PMID- 30201529
TI  - Establishment of the first International Standard for human anti-typhoid capsular
      Vi polysaccharide IgG.
AB  - Vi capsular polysaccharide (Vi) conjugate vaccines, which can prevent typhoid in
      infants and young children, are being developed. Comparative immunogenicity
      studies are facilitated by an International Standard (IS) for human anti-Vi IgG.
      16/138, a pool of sera from volunteers which received either Vi conjugate vaccine
      or plain Vi vaccine, was assessed as an IS alongside U.S. reference reagent Vi
      IgGR1, 2011. Samples were tested in a commercial ELISA (n = 7), a standardised
      ELISA based on biotinylated Vi (n = 7) and in-house ELISAs (n = 7). Valid
      estimates were obtained for the potency of all samples in the commercial ELISA,
      and the commutability of 16/138 and Vi-IgGR1, 2011 was evident for the commercial
      ELISA and in-house ELISAs based on a coating of Vi and protein. The WHO Expert
      Committee on Biological Standardization established 16/138 as the first IS for
      anti-Vi IgG with 100 IU per ampoule and assigned 163 IU per vial of Vi-IgGR1,
      2011.

PMID- 30201530
TI  - Impact of Reducing Pre-Hospital Delay in Response to Heart Attack Symptoms in
      Australia.
AB  - BACKGROUND: This research estimates the broader socioeconomic impacts of reducing
      pre-hospital delay times across Australia in patients with heart attack symptoms.
      METHODS: A cost benefit analysis (CBA) was undertaken to demonstrate the costs
      and benefits of a public awareness/education campaign to reduce pre-hospital
      delay time from 5.2hours (Base Case) to 4.1hours (Scenario 1) and 2.0hours
      (Scenario 2). All assumptions underlying the CBA are supported by academic
      literature. Financial impacts considered include campaign/public education costs,
      direct inpatient costs and long-term health care costs. Socioeconomic impacts
      considered include burden of disease, productivity losses, informal care costs
      and net deadweight loss. RESULTS: The campaign is expected to generate an
      additional net benefit of $41.2-139.1 million in comparison to the Base Case,
      resulting in a benefit cost ratio (BCR) of 3.23-5.06. Disability Adjusted Life
      Years (DALYs) reduced by 6,046-7,575 years. CONCLUSION: This research illustrates
      that an investment in public awareness/education campaign can generate
      considerable benefits, more than offsetting the costs associated with the
      campaign and keeping people living longer such as ongoing health care costs.
      However, significant effort, supplementary strategies and sustained investment
      will be required to ensure the impact and benefit is sustained over the long
      term.

PMID- 30201531
TI  - Circulating oleic acid levels are related to greater risks of cardiovascular
      events and all-cause mortality: The multi-ethnic study of atherosclerosis.
AB  - BACKGROUND: Limited evidence has suggested that circulating levels of the omega-9
      fatty acid, oleic acid, may be related to greater risks of adverse cardiovascular
      outcomes. OBJECTIVE: We aimed to determine whether plasma oleic acid may be
      independently associated with clinical and subclinical cardiovascular disease
      (CVD) and all-cause mortality in a large multiethnic cohort. METHODS: Plasma
      fatty acids were measured by gas chromatography-flame ionization in 6568
      participants of the Multi-Ethnic Study of Atherosclerosis. The presence of
      coronary artery calcium (CAC) and aortic valve calcification (AVC) was determined
      by computed tomography, and carotid plaque was assessed by ultrasound. Incident
      CVD was defined as myocardial infarction, fatal coronary heart disease,
      resuscitated cardiac arrest, stroke, or stroke death. Heart failure (HF) was
      adjudicated from clinical records. Relative risk regression estimated plasma
      oleic acid-related rate ratios for prevalent CAC, AVC, and carotid plaque. Cox
      regression estimated hazard ratios (HRs) for CVD, HF, and all-cause mortality
      over a median 13-year follow-up. RESULTS: Individuals in top quartiles of oleic
      acid showed greater rate ratios of CAC, AVC, and carotid plaque (all P < .001),
      but associations were rendered nonsignificant after adjustment for other risk
      factors. By contrast, those in top quartiles of plasma oleic acid showed
      significantly greater risks of incident HF (HR: 2.03; P < .001), CVD (HR: 1.41; P
      = .008), and all-cause mortality (HR: 1.55; P < .001) than those in referent
      quartiles independent of typical risk factors as well as plasma omega-3 fatty
      acid levels. CONCLUSIONS: Plasma oleic acid appears to be a risk factor for CVD
      events and all-cause mortality independent of typical risk factors and plasma
      omega-3 fatty acids. Additional studies are warranted for confirmation and to
      further examine whether plasma oleic acid directly contributes to, or serves as a
      marker of, disease pathogenesis. These findings should not be extrapolated to
      dietary oleic acid intake.

PMID- 30201532
TI  - Paradoxical fall in proteinuria during pregnancy in an LCAT-deficient patient-A
      case report.
AB  - A 29-year-old lady was diagnosed with lecithin:cholesterol acyltransferase (LCAT)
      deficiency having presented with bilateral corneal clouding, severely reduced
      high density lipoproteins cholesterol, and proteinuria. She is a compound
      heterozygote with two LCAT gene mutations, one of which is novel, c.321C>A in
      exon 3. Surprisingly, the level of proteinuria significantly improved during
      pregnancy, despite stopping the angiotensin-converting enzyme inhibitor. However,
      LCAT concentration and activity remained identical during pregnancy and
      postpartum. Her pregnancy was complicated by rising triglyceride levels from the
      second trimester requiring treatment with omega-3 fatty acid and fenofibrate. In
      the last trimester, a further complication arose when she became hypertensive and
      proteinuria worsened. She was diagnosed with pre-eclampsia and had an emergency
      cesarean section at 39 weeks delivering a healthy baby. This case adds to the
      knowledge of the pathophysiology of LCAT deficiency during pregnancy and will be
      useful in future patient management.

PMID- 30201533
TI  - Injections to pregnant mice produce prenatal stress that affects aggressive
      behavior in their adult male offspring.
AB  - Maternal stress could reprogram the developing fetal nervous system. A common
      target of maternal glucocorticoids is fetal neuro-endocrine axis. In the present
      study, pregnant mice were exposed to stress by injection and their male offspring
      were tested for sexual and aggressive behaviors in adult life. Three groups of
      pregnant mice were exposed to stress by sham syringe injection. The first group
      was injected on days 13, 14, and 15 p.c., the second group was injected on days
      17 and 18 p.c., and the third group was injected daily from days 13 to 18 p.c.
      while control mice were not injected. Male offspring that were exposed to stress
      on days 13-18 p.c. and 17-18 p.c. were less aggressive and had lower blood
      testosterone levels in comparison to the control group. In male sexual behavior,
      there were no statistically significant differences between the groups. Body
      weight differed significantly with groups injected on days 13-18 p.c. and 13-15
      p.c. having significantly higher body weight in adult life than the other two
      groups. After behavioral testing, brains were processed for immunohistochemical
      staining with antibodies against vasopressin (AVP) and calbindin (CALB). The
      expression of AVP and CALB in the lateral septum and in the preoptic area,
      respectively, did not differ between groups, suggesting that these two
      masculinization markers were not affected by prenatal stress. Present study
      therefore shows that even presumably mild and short prenatal stress weakens
      aggressive behavior of adult male mice, possibly due to reduced testosterone
      levels in blood.

PMID- 30201534
TI  - Incidence, outcomes and guideline compliance of out-of-hospital maternal cardiac
      arrest resuscitations: A population-based cohort study.
AB  - BACKGROUND: Incidence and survival rates after cardiac arrest among pregnant
      women are reported for in-hospital cardiac arrests; the incidence and outcomes of
      maternal out-of-hospital cardiac arrest (OHCA) are unknown. Current
      cardiopulmonary resuscitation guidelines contain recommendations specific to this
      population; compliance with these has not been investigated. OBJECTIVE: To report
      maternal OHCA incidence, outcomes, and compliance with recommended treatment
      guidelines. METHODS: A population-based cohort study of consecutive maternal
      OHCAs from 2010 to 2014. Census data of all women of childbearing age provided
      the comparison. Resuscitation performance was measured against the 2010 American
      Heart Association (AHA) Guidelines. RESULTS: Six maternal OHCAs were identified
      among 1085 OHCAs occurring in females of child bearing age (15-49) years;
      Incidence 1.71 per 100,000 pregnant women (95% CI 0.21 to 6.18) vs. 20.18 OHCAs
      per 100,000 females of child bearing age (95% CI, 18 to 22.62) p < 0.0001.
      Survival to hospital discharge was 16.7% (95% CI 3.0, 56.4%) after maternal OHCA
      vs. 6.8% (95% CI 5.4, 8.4) p < 0.0001 after OHCA in all females of childbearing
      age, and neonatal survival was 33.3% (95% CI 9.7, 70%). CPR quality metric
      compliance averaged 83% (range 75% to 100%); compliance with pregnancy-specific
      resuscitation guidelines ranged from 0% (uterine displacement) to 100%
      (intravenous line insertion above diaphragm and prehospital maternal team
      activation). CONCLUSION: The incidence of maternal OHCA was 1.71:100,000.
      Survival was higher after maternal OHCA than after OHCA of non-pregnant females
      of childbearing age. Pregnancy-specific guideline compliance was low suggesting a
      need for training and better documentation to improve outcomes in these rare
      events.

PMID- 30201535
TI  - Factors associated with health-related quality of life among cardiac arrest
      survivors treated with an implantable cardioverter-defibrillator.
AB  - AIM: To explore factors associated with health-related quality of life (HRQoL)
      among cardiac arrest (CA) survivors treated with an implantable cardioverter
      defibrillator (ICD) in relation to gender, and to compare their HRQoL with a
      general population. METHODS: This cross-sectional study included 990 adults
      treated with an ICD after suffering CA. All participants received a questionnaire
      including demographics, comorbidities and instruments to measure HRQoL (EQ-5D-3L
      and HADS), ICD-related concerns (ICDC), perceived control (CAS), and type D
      personality (DS-14). HRQoL (EQ-5D-3L) was compared to a general Swedish
      population, matched for age and gender. Linear regression analyses were used to
      explore factors associated with HRQoL. RESULTS: The CA survivors reported better
      HRQoL in EQ index and less pain/discomfort compared to the general population (p
      < 0.001). In contrast, they reported more problems in mobility and usual
      activities (p < 0.01). Problems with anxiety and depression were reported by
      15.5% and 7.4% respectively. The following factors were independently associated
      with all aspects of worse HRQoL: being unemployed, suffering more comorbidity,
      perceiving less control, and having a type D personality. Further, being female
      and suffering ICD-related concerns were independently associated with worse HRQoL
      in three of the four final regression models. CONCLUSIONS: This extensive
      population-based study showed that most CA survivors living with an ICD rate
      their HRQoL as acceptable. In addition, their HRQoL is similar to a general
      population. Women reported worse HRQoL compared to men. Several factors
      associated with HRQoL were identified, and might be used when screening patients
      for health problems and when developing health promoting interventions.

PMID- 30201536
TI  - Diagnostic Yield of Non-Invasive Imaging in Patients Following Non-Traumatic Out
      of-Hospital Sudden Cardiac Arrest: A Systematic Review.
AB  - AIM: To review data for non-invasive imaging in the diagnosis of non-traumatic
      out-of-hospital cardiac arrest (OHCA). DATA SOURCES: We searched MEDLINE, EMBASE,
      Cochrane library, and clinicaltrials.gov databases from inception to January 2017
      for studies utilizing non-invasive imaging to identify potential causes of OHCA
      [computed tomography (CT), ultrasound including echocardiography, and magnetic
      resonance (MRI)]. STUDY SELECTION: Inclusion criteria were the following: 1)
      randomized control trials, cohort studies or observational studies; 2) contained
      a population >=18 years old with non-traumatic OHCA who underwent diagnostic
      imaging with CT, MRI, echocardiography, or abdominal ultrasound; 3) imaging was
      obtained for diagnostic purposes; 4) patients were alive or were undergoing
      cardiopulmonary resuscitation at the time of imaging; 5) contained potential
      causes of OHCA. Endpoints studied were the number of potential OHCA causes
      identified, diagnostic accuracy measures (sensitivity, specificity, positive and
      negative predictive values), and diagnostic utility (number of imaging findings
      with reported changes in clinical management). RESULTS: Of the total 5,722
      studies identified, 17 (0.3%) met inclusion criteria. The majority of studies
      assessed the utility of CT in OHCA (n = 10), and potential causes of OHCA were
      found in 8-54% of patients following head, abdominal and/or chest CT. Only 1/17
      (6%) studies reported diagnostic accuracy measures, and 9/17 (53%) studies
      included a time to imaging criteria within 24 hours. CONCLUSION: Although non
      invasive imaging is commonly performed in patients after OHCA, its diagnostic
      utility remains poorly characterized. Prospective studies are needed for
      appropriate imaging selection and their potential impact on treatment and
      outcome.

PMID- 30201537
TI  - ERalpha and/or ERbeta activation ameliorates cognitive impairment, neurogenesis
      and apoptosis in type 2 diabetes mellitus mice.
AB  - Estrogen receptors (ERs) are thought to be associated with the onset and
      progression of neurodegenerative injuries and diseases, but the relationship and
      mechanisms underlying between ERs and cognition in type 2 diabetes remain
      elusive. In the current study, we investigated the effects of ERalpha and ERbeta
      on the cognition, neurogenesis and apoptosis in high-fat diet and streptozocin
      induced diabetic mice. We found that ERalpha and/or ERbeta activation using their
      agonists (0.5 mg/kg E2, PPT or DPN) ameliorate memory impairment in the Morris
      water maze and Y-maze tests, increase hippocampal neurogenesis and prevent
      hippocampal apoptotic responses. Importantly, treatment with the pharmacologic
      ERs agonists caused significant increases in the membrane ERalpha and ERbeta
      expression and subsequent PI3K/Akt, CREB and BDNF activation in the hippocampus
      of type 2 diabetes mellitus mice. Our data indicate that ERalpha and ERbeta are
      involved in the cognitive impairment in type 2 diabetes, and that activated ERs,
      such as application of ERs agonists, could be a novel and promising strategy for
      the treatment of diabetic cognitive impairment.

PMID- 30201538
TI  - Nicotine pharmacokinetics of electronic cigarettes: A review of the literature.
AB  - E-cigarettes are battery-powered electronic devices from which users can inhale
      nicotine following its aerosolisation from a liquid solution. Some regulators and
      public health bodies consider e-cigarettes as potentially playing a major role in
      tobacco harm reduction. Their ability to provide nicotine to smokers in both
      amount and in a manner and form generally similar to cigarette smoking have been
      proposed as key components to help smokers reduce or cease the use of combustible
      cigarettes. Nicotine pharmacokinetic studies of e-cigarettes have been performed
      for a number of years and are beginning to show how nicotine delivery is evolving
      as the products themselves evolve. In this review, we provide a critical overview
      of the literature to describe what is known about nicotine delivery from e
      cigarettes. We will discuss how the progression of e-cigarette design,
      development, and user familiarity has allowed increases in nicotine availability
      to the user, in the context of how much and how rapidly nicotine is delivered
      during acute-use periods. This review will also provide insight into current
      research gaps and highlight the potential utility of modelling and the
      standardisation of methodologies used to assess nicotine delivery to facilitate
      identification of products that are best suited to displace cigarette smoking
      among adult smokers.

PMID- 30201539
TI  - Structural and functional pharmacokinetic analogs for physiologically based
      pharmacokinetic (PBPK) model evaluation.
AB  - Physiologically based pharmacokinetic (PBPK) models enable simulations of
      absorption, distribution, metabolism, and elimination of chemicals from the body.
      Model evaluation is a key step in the PBPK model development processes whereby
      model predictions are compared to pharmacokinetic (PK) data. A prerequisite for
      PBPK model evaluation has always been the availability of PK data for the modeled
      compound, a requirement which has limited the use and acceptance of PBPK models
      since PK data is often limited or not available. The current work tests the
      hypothesis that an adequately developed PBPK model for a target chemical
      (chemical with no PK data) can be evaluated using PK data from a source chemical
      (chemical with existing PK data). Two different approaches for identifying the
      source chemical, a structural PK analog and functional PK analog technique, are
      used to evaluate a series of oral human PBPK models. Results show that both
      analog approaches can identify PK analogs which display similar PK as the target
      chemical and can be used as alternative ways for evaluating PBPK models. As
      animal free safety assessment strategies continue to develop, it's important to
      develop alternative approaches for PBPK model evaluation which does not rely on
      generating new PK data.

PMID- 30201540
TI  - Association between Clostridioides difficile ribotypes, restriction endonuclease
      analysis types, and toxin gene expression.
AB  - OBJECTIVES: Clostridioides difficile strains cause severe infection. Previous
      studies suggested that the virulence of C. difficile is dependent on ribotype;
      however, this hypothesis is still controversial. We aim to investigate the
      relationship between ribotypes, restriction endonuclease analysis (REA) types,
      and toxin gene expression in C. difficile strains. METHODS: We utilized 53
      clinical C. difficile strains. All strains were assigned a molecular strain type
      using PCR ribotyping and REA typing and classified into 17 ribotypes and six REA
      types. The expression of toxin genes (tcdA, tcdB, and cdtB) in C. difficile
      strains were quantified by real-time PCR using each specific primer set, and
      expression was normalized to that of the housekeeping gene rpoA. RESULTS: All 53
      strains expressed tcdB and four strains expressed cdtB. Five strains did not
      express tcdA. Most ribotype and REA type strains expressed tcdA and tcdB similar
      to the BAA-1870 strain. In cdtB-positive strains, the cdtB expression levels were
      similar to those in the BAA-1870 strain. tcdA and tcdB expression levels were
      similar in the cdtB-positive and cdtB-negative strains. CONCLUSION: Toxin gene
      expression was not associated with the ribotype. Production of binary toxin C.
      difficile transferase was not related to tcdA and tcdB expression levels.

PMID- 30201541
TI  - Sex and species differences of stress markers in sympatric cheetahs and leopards
      in Namibia.
AB  - Physiological stress markers may provide valuable insight for our understanding
      of costs of given life-history strategies or of wildlife health condition, most
      importantly in case of threatened species. In the last decade, there has been
      growing interest in the ecological relevance of cellular oxidative stress, which
      would provide complimentary information to that obtained by the classic analyses
      of glucocorticoid hormones. In this study, we analysed the sex and species
      variation of five blood-based markers of oxidative status, both molecular
      oxidative damage and antioxidant protection, in sympatric cheetahs (Acinonyx
      jubatus) and leopards (Panthera pardus) living on Namibian farmlands. Both these
      terrestrial carnivores are classified as vulnerable by the International Union
      for Conservation of Nature. We found that female cheetahs had significantly
      higher serum reactive oxygen metabolites of non-protein origin and lower
      glutathione peroxidase activity in whole blood than both male and female leopards
      and male cheetahs. We also found that cheetahs and leopards differed in the
      association between the two antioxidant enzymes glutathione peroxidase and
      superoxide dismutase. Correlations among oxidative status markers were stronger
      in female cheetahs than leopards or male cheetahs. Our results suggest that
      female cheetahs are more sensitive to local sources of stress. Our work did not
      corroborate the assumption that two species with different life histories
      consistently differ in key physiological traits.

PMID- 30201542
TI  - Molecular characterization of a pattern recognition protein LGBP highly expressed
      in the early stages of mud crab Scylla paramamosain.
AB  - The early developmental stages of the mud crab Scylla paramamosain suffer from
      high mortality caused by pathogen infections; however, few immune associated
      factors are known. Lipopolysaccharide and beta-1,3-glucan-binding protein (LGBP)
      functions as a typical pathogen recognition receptor and plays an important role
      in the innate immune system of invertebrates. In this study we characterized a
      LGBP gene (SpLGBP) which was highly expressed in the late embryonic, zoea I
      larval stage and hepatopancreas of S. paramamosain.. It encodes 364 amino acids,
      composed of several conserved domains like the bacterial glucanase motif. The
      recombinant SpLGBP protein (rSpLGBP) was obtained through the E.coli expression
      system, in which two 6?His-tags were added to both C and N terminals during
      vector construction for the improvement of purification efficiency. In vivo the
      study showed that the SpLGBP mRNA was significantly up-regulated under Vibrio
      parahaemolyticus and a lipopolysaccharide (LPS) challenge in the hemocytes and
      hepatopancreas. The ELISA binding assay in vitro indicated that the rSpLGBP was
      capable of binding to LPSs and peptidoglycan (PGN). The rSpLGBP could agglutinate
      both G+ and G- bacteria in the presence of Ca2+. Our results suggest that SpLGBP
      may play an immunological role against pathogenic infection in the early
      developmental stages of S. paramamosain.

PMID- 30201543
TI  - Regulation of mitochondrial biosynthesis and function by dietary carbohydrate
      levels and lipid sources in juvenile blunt snout bream Megalobrama amblycephala.
AB  - This study aimed to investigate the effects of dietary non-protein energy
      adjustments on the mitochondrial biosynthesis and function of juvenile
      Megalobrama amblycephala. Fish (average weight: 37.98 +/- 0.07 g) were fed eight
      diets containing two dietary carbohydrate levels (30% and 43%) and four lipid
      sources (fish oil, soybean oil, palm oil and the mixed oil) for 11 weeks. Liver
      mitochondrial respiratory chain complex V activity and ATP (adenosine
      triphosphate) content both increased significantly with increasing dietary
      carbohydrate levels, whereas the opposite was true for the AMP (adenosine 5'
      monophosphate)/ATP ratio, hepatic transcripts of AMP-activated protein kinase
      alpha1 (AMPKalpha1), AMPKalpha2, peroxisome proliferators gamma-activated
      receptor coativator-1alpha (PGC-1alpha), NADH dehydrogenase 1 and cytochrome c
      oxidase 1 (COX1) as well as the activities of Na+-K+-ATPase, succinate
      dehydrogenase (SDH), citrate synthase (CS) and mitochondrial respiratory chain
      complex I, III and IV. Additionally, hepatic ATP content, the transcripts of
      AMPKalpha, COX1 and ATP6 and the activities of Na+-K+-ATPase, SDH, CS and
      mitochondrial respiratory chain complex III were all significantly affected by
      lipid sources. Furthermore, an interaction between dietary carbohydrate levels
      and lipid sources was also observed in the activities of liver mitochondrial Na+
      K+-ATPase and respiratory chain complex III as well as the transcripts of ATP6
      and PGC-1alpha. Overall, these findings suggested that dietary carbohydrate
      levels and lipid sources remarkably affected the mitochondrial biosynthesis and
      function of M. amblycephala. A diet containing 30% carbohydrate and FO could
      boost its mitochondrial biosynthesis, while that of 30% carbohydrate and SO could
      enhance the mitochondrial function.

PMID- 30201544
TI  - Morphea "En Coup De Sabre" at the Site of Healed Herpes Zoster Ophthalmicus.

PMID- 30201546
TI  - Never Thought I Would.

PMID- 30201545
TI  - Estimated GFR and Hospital-Acquired Infections Following Major Surgery.
AB  - RATIONALE & OBJECTIVE: Low estimated glomerular filtration rate (eGFR) increases
      infection risk, but its contribution to hospital-acquired infection following
      major surgery is unknown. STUDY DESIGN: Retrospective cohort study. SETTING &
      PARTICIPANTS: Residents of Stockholm, Sweden, 18 years or older with at least 1
      recorded serum creatinine measurement, no recent diagnoses of infection, and
      hospitalized for orthopedic, abdominal, cardiothoracic and vascular, or
      neurologic surgery between January 2007 and December 2011. EXPOSURES:
      eGFR<60mL/min/1.73m2 (termed low eGFR) and other clinical comorbid conditions at
      admission: cancer, cerebrovascular disease, chronic obstructive pulmonary disease
      (COPD), coronary heart disease, diabetes, heart failure (HF), and liver disease.
      OUTCOMES: Incidence and population-attributable fractions of 4 major types of
      hospital-acquired infections: pneumonia, urinary tract infection, surgical-site
      infection, and bloodstream infection. ANALYTICAL APPROACH: Logistic regression
      analysis. RESULTS: 66,126 patients with a history of orthopedic (n=31,630),
      abdominal (n=26,317), cardiothoracic and vascular (n=6,266), or neurologic
      (n=1,913) surgery were studied. Cancer (21%) and low eGFR (18%) were the most
      prevalent comorbid conditions at admission, followed by diabetes, HF, and COPD
      (12%). Overall, 3,617 patients (5.5%) had at least 1 type of hospital-acquired
      infection (1,650 cases of urinary tract infection, 1,196 cases of pneumonia, 635
      cases of surgical site infection, and 411 cases of bloodstream infection). The OR
      of hospital-acquired infection was highest for low eGFR (1.64; 95% CI, 1.51
      1.77), followed by HF (1.60; 95% CI, 1.46-1.76), cerebrovascular disease (1.47;
      95% CI, 1.34-1.61), cancer (1.43; 95% CI, 1.33-1.55), and COPD (1.37; 95% CI,
      1.25-1.50). Low eGFR demonstrated the highest population-attributable fraction
      for hospital-acquired infections (0.13), followed by cancer (0.10), HF (0.09),
      and cerebrovascular disease (0.06). When assessed by type of infection, low eGFR
      particularly contributed to pneumonia (0.15) and urinary tract infection (0.10).
      LIMITATIONS: Outcome ascertainment based on diagnostic codes. CONCLUSIONS: These
      findings highlight the association between low eGFR and hospital-acquired
      infection and may inform evidence-based hospital-acquired infection prevention
      policies following major surgery.

PMID- 30201547
TI  - Use of Renin-Angiotensin System Blockade in Advanced CKD: An NKF-KDOQI
      Controversies Report.
AB  - Multiple clinical trials have demonstrated that renin-angiotensin system (RAS)
      blockade with either angiotensin-converting enzyme inhibitors or angiotensin
      receptor blockers effectively reduces chronic kidney disease (CKD) progression.
      However, most clinical trials excluded participants with advanced CKD (ie,
      estimated glomerular filtration rate [eGFR]<30mL/min/1.73m2). It is acknowledged
      that initiation of RAS blockade is often associated with an acute reduction in
      eGFR, which is thought to be functional, but may result in long-term preservation
      of kidney function through the reductions in glomerular intracapillary pressure
      conferred by these agents. In this National Kidney Foundation-Kidney Disease
      Outcomes Quality Initiative (NKF-KDOQI) report, we discuss the controversies
      regarding use of RAS blockade in patients with advanced kidney disease. We review
      available published data on this topic and provide perspective on the impact of
      RAS blockade on changes in eGFRs and potassium levels. We conclude that more
      research is needed to evaluate the therapeutic index of RAS blockade in patients
      with advanced CKD.

PMID- 30201549
TI  - Color vision impairments in schizophrenia and the role of antipsychotic
      medication type.
AB  - Schizophrenia patients (SCZ) demonstrate deficits in many domains of mental
      functioning, including visual perception. An issue that has been relatively
      unexplored, in terms of explaining variation in visual function in SCZ, however,
      is medication use. The present study explored potential medication effects on
      color vision in SCZ, a process that is strongly linked to dopaminergic function
      in the retina. SCZ patients who had clear-cut either typical (n = 29) or atypical
      (n = 29) monotherapy, without any other concurrent medication, and a group of age
      and gender-matched healthy controls participated in the study. Color vision was
      assessed by the Cambridge Colour Test, using the Trivector and Ellipse subtests.
      The results demonstrated impaired color perception in patients with
      schizophrenia, especially in those receiving typical antipsychotics, but these
      deficits were subtle and not generalized to all parameters. Our findings are
      consistent with the known neurophysiology of the retina and visual pathways, and
      with the effects of dopamine blocking medications, but the results should be
      carefully interpreted.

PMID- 30201548
TI  - Transplantation of a Gitelman Syndrome Kidney Ameliorates Hypertension: A Case
      Report.
AB  - Gitelman syndrome is caused by inactivating mutations of the gene that encodes
      the renal sodium/chloride cotransporter (NCC; encoded by SLC12A3), resulting in
      hypokalemia, hypomagnesemia, hypocalciuria, and metabolic alkalosis. Renal salt
      wasting commonly provokes mild hypotension. The paucity of previous kidney
      transplants from donors with known tubulopathies suggests that such conditions
      may be considered contraindications to donation. A 76-year-old man received a
      live unrelated kidney transplant from a donor with known Gitelman syndrome
      secondary to a pathogenic mutation of SLC12A3. Immediate graft function preceded
      the emergence of the Gitelman syndrome biochemical phenotype and blood pressure
      subsequently improved. The recipient developed unexpected hyponatremia. Potential
      causes are discussed, including the possibility that it paralleled the
      physiologic changes seen in the high-volume state of thiazide-induced
      hyponatremia. Transplanted kidneys are subject to nephrotoxicity from the use of
      calcineurin inhibitors. Acquired Gitelman syndrome may confer a potential long
      term advantage to the recipient through both improved blood pressure control and
      protection against the calcineurin inhibitor-induced side-effect profile caused
      by NCC overactivation. Both the donor and recipient remain well. In conclusion,
      Gitelman syndrome need not preclude kidney donation and transference of the
      phenotype may have benefits for the recipient.

PMID- 30201550
TI  - Elevated allostatic load index is associated with working memory deficits in
      first-episode psychosis.

PMID- 30201551
TI  - Association between phosphodiesterase type 5 inhibitors and prostate cancer: A
      systematic review.
AB  - INTRODUCTION: We aim to assess the effect of phosphodiesterase type 5 inhibitors
      (PDE5I) on prostate cancer risk as well on biochemical recurrence after radical
      prostatectomy. METHOD: We performed a research using the following keywords
      "Phosphodiesterase type 5 inhibitors" and "Prostate cancer". Only trials
      examining the effect of PDE5I on prostate cancer risk and recurrence after
      radical prostatectomy were included. RESULTS: Seventeen preclinical trials and
      seven clinical trials were included. Preclinical studies demonstrate a pivotal
      role for PDE5I as a modulator of apoptosis preventing prostate carcinogenesis.
      The clinical benefit of PDE5I was not demonstrated. PDE5I use was not associated
      with decreased prostate cancer diagnosis in two retrospective cohort studies.
      Biochemical recurrence after radical prostatectomy was not lower (nor higher) in
      patients taking PDE5I in three retrospective case match studies. CONCLUSION:
      Based on this review, a change in our practice regarding pharmacological
      reeducation after radical prostatectomy is not justified.

PMID- 30201552
TI  - [Priapism: Diagnosis and management].
AB  - OBJECTIVE: Our aim was to present a synthesis on the diagnosis and treatment of
      priapism. METHODS: For this purpose, a literature search was performed through
      PubMed to analyze literature reviews and guidelines regarding priapism. RESULTS:
      Priapism is an erection that persists more than 4hours. There are 3 types of
      priapism: ischemic priapism, non-ischemic priapism and recurrent (stuttering)
      priapism. Ischemic priapism, often idiopathic, is the most frequent. When
      diagnosed, an urgent management is required to limit erectile dysfunction. Sickle
      cell patients are prone to have ischemic and stuttering priapism. Non-ischemic
      priapism usually occurs after perineal trauma. Priapism management depends on the
      type of priapism. Medical treatment (corporal aspiration and injection of
      sympathomimetics) then if failed, surgery are indicated for ischemic priapism.
      The persistence of a non-ischemic priapism most likely requires a radiologic
      embolization. CONCLUSION: Priapism is a condition that often requires emergency
      treatment to spare erectile function. It appears crucial to know this condition
      and its management.

PMID- 30201553
TI  - System insights into hemostasis: Open questions and the role of mathematical
      modelling: Comment on "Modeling thrombosis in silico: Frontiers, challenges,
      unresolved problems and milestones" by A.V. Belyaev et al.

PMID- 30201554
TI  - iRNA(m6A)-PseDNC: Identifying N6-methyladenosine sites using pseudo dinucleotide
      composition.
AB  - As a prevalent post-transcriptional modification, N6-methyladenosine (m6A) plays
      key roles in a series of biological processes. Although experimental technologies
      have been developed and applied to identify m6A sites, they are still cost
      ineffective for transcriptome-wide detections of m6A. As good complements to the
      experimental techniques, some computational methods have been proposed to
      identify m6A sites. However, their performance remains unsatisfactory. In this
      study, we firstly proposed an Euclidean distance based method to construct a high
      quality benchmark dataset. By encoding the RNA sequences using pseudo nucleotide
      composition, a new predictor called iRNA(m6A)-PseDNC was developed to identify
      m6A sites in the Saccharomyces cerevisiae genome. It has been demonstrated by the
      10-fold cross validation test that the performance of iRNA(m6A)-PseDNC is
      superior to the existing methods. Meanwhile, for the convenience of most
      experimental scientists, established at the site http://lin
      group.cn/server/iRNA(m6A)-PseDNC.php is its web-server, by which users can easily
      get their desired results without need to go through the detailed mathematics. It
      is anticipated that iRNA(m6A)-PseDNC will become a useful high throughput tool
      for identifying m6A sites in the S. cerevisiae genome.

PMID- 30201555
TI  - In situ decay of polyfluorinated benzoic acids under anaerobic conditions.
AB  - Polyfluorinated benzoic acids (PBAs) can be used as non-reactive tracers to
      characterize reactive mass transport mechanisms in groundwater. The use of PBAs
      as non-reactive tracers assumes that their reactivities are negligible. If this
      assumption is not valid, PBAs may not be appropriate to use as non-reactive
      tracers. In this study, the reactivity of two PBAs, 2,6-difluorobenzoic acid (2,6
      DFBA) and pentafluorobenzoic acid (PFBA), was tested in situ. A series of two
      single-well push-pull tests were conducted in two hydrogeologically similar, yet
      spatially distinct, groundwater monitoring wells. Bromide, 2,6-DFBA, and PFBA
      were added to the injection fluid and periodically measured in the extraction
      fluid along with chloride, nitrate, sulfate, and fluoride. Linear regression of
      the dilution-adjusted breakthrough curves of both PBAs indicated zero-order decay
      accompanied by nitrate and subsequent sulfate removal. The dilution-adjusted
      breakthrough curves of chloride, a non-reactive halide similar to bromide, showed
      no evidence of reactivity. These results strongly suggested that biodegradation
      of both PBAs occurred under anaerobic conditions. The results of this study
      implied that PBAs may not be appropriate to use as non-reactive tracers in
      certain hydrogeologic settings, presumably those where they can serve as carbon
      and/or electron donors to stimulate microbial activity. Future studies would
      benefit from using ring-14C-labeled PBAs to determine the fate of carbon combined
      with microbial analyses to characterize the PBA-degrading members of the
      microbial community.

PMID- 30201556
TI  - Competitive transport processes of chloride, sodium, potassium, and ammonium in
      fen peat.
AB  - There is sparse information on reactive solute transport in peat; yet, with
      increasing development of peatland dominated landscapes, purposeful and
      accidental contaminant releases will occur, so it is important to assess their
      mobility. Previous experiments with peat have only evaluated single-component
      solutions, such that no information exists on solute transport of potentially
      competitively adsorbing ions to the peat matrix. Additionally, recent studies
      suggest chloride (Cl-) might not be conservative in peat, as assumed by many past
      peat solute transport studies. Based on measured and modelled adsorption
      isotherms, this study illustrates concentration dependent adsorption of Cl- to
      peat occurred in equilibrium adsorption batch (EAB) experiments, which could be
      described with a Sips isotherm. However, Cl- adsorption was insignificant for low
      concentrations (<500 mg L-1) as used in breakthrough curve experiments (BTC). We
      found that competitive adsorption of Na+, K+, and NH4+ transport could be
      observed in EAB and BTC, depending on the dissolved ion species present. Na+
      followed a Langmuir isotherm, K+ a linear isotherm within the tested
      concentration range (~10 - 1500 mg L-1), while the results for NH4+ are
      inconclusive due to potential microbial degradation. Only Na+ showed clear
      evidence of competitive behaviour, with an order of magnitude decrease in maximum
      adsorption capacity in the presence of NH4+ (0.22 to 0.02 mol kg-1), which was
      confirmed by the BTC data where the Na+ retardation coefficient differed between
      the experiments with different cations. Thus, solute mobility in peatlands is
      affected by competitive adsorption.

PMID- 30201557
TI  - Early Weight-Bearing After Arthrodesis of the First Metatarsal-Phalangeal Joint:
      A Systematic Review of the Incidence of Non-Union.
AB  - Arthrodesis of the first metatarsal-phalangeal joint is a reliable procedure for
      correction of both hallux limitus/rigidus and severe hallux abducto valgus
      deformities. However, 1 potential contraindication to the procedure is the
      extended period of non-weight-bearing immobilization that is typically associated
      with the postoperative course. The objective of this investigation was to perform
      a systematic review of the incidence of non-union after early weight bearing in
      patients who underwent arthrodesis of the first metatarsal-phalangeal joint. We
      performed a review of electronic databases with the inclusion criteria of
      retrospective case series, retrospective clinical cohort analyses, and
      prospective clinical trials with n >= 15 feet, a mean follow-up of >=12 months, a
      defined postoperative early weight-bearing protocol (defined as <=2 weeks), a
      clear description of the fixation construct, a reported incidence rate of non
      union, and patients who underwent primary surgery for hallux abducto valgus or
      hallux limitus/rigidus deformities. Seventeen studies met our inclusion criteria,
      with a total of 898 feet analyzed. Of these, 57 (6.35%) were described as
      developing a non-union. This would likely be considered an acceptable crude,
      heterogeneous incidence of non-union when considering this procedure. It might
      also indicate that arthrodesis of the first metatarsal-phalangeal joint does not
      always require an extended period of non-weight-bearing postoperative
      immobilization.

PMID- 30201558
TI  - The use of chitosan as a bioactive polysaccharide in non-invasive detection of
      malondialdehyde biomarker in human exhaled breath condensate: A new platform
      towards diagnosis of some lung disease.
AB  - Herein, a reusable and time-saving strategy for the electrochemical
      polymerization of dopamine (EPD) is reported. In this work, biocompatible polymer
      chitosan (CS) was electrodeposited on the surface of PDA modified glassy carbon
      electrode. Owing to the abundant catechol and amine groups in the PDA layer,
      uniform silver nanoparticles (Ag NPs) are deposited onto the POLY(DA-CS) and can
      effectively prevent the recombination of electron-hole pairs generated from photo
      electrocatalysis and transfer the captured electrons to participate in the photo
      electrocatalytic reaction process. Compared with pristine POLY(DA-CS), the as
      prepared POLY(DA-CS)-AgNPs organic-inorganic hybrid exhibit electrochemical
      sensitivity for detecting MDA and display excellent durability. Furthermore, the
      mussel-inspired electropolymerization strategy and the fast EPD-Ag nanoparticle
      decorating process presented herein can be readily extended to various biomedical
      analysis and lung cancer detection. It is the adaptation of the established
      POLY(DA-CS)-Ag NPs organic-inorganic hybrid for a selective, robust, and
      generalizable sensing system that is the emphasis of this work.

PMID- 30201559
TI  - Extraction and incorporation of bioactives into protein formulations for food and
      biomedical applications.
AB  - Bioactive compounds from natural resources have been pointed out as promising
      substances with great benefits for human health. Furthermore, new techniques for
      their extraction have been reviewed in order to consider a global approach taking
      economic and environmental issues into account. Additionally, the incorporation
      of these biologically active compounds into protein-based products manufactured
      via different processing methods, such as solution casting, compression moulding,
      electrospinning, freeze-drying, and 3D printing, has been assessed, since the
      design and manufacturing method employed have a direct influence into the final
      properties of the material. Hence, new opportunities to develop active
      biopolymeric materials with great potential in food and biomedical applications
      have been presented. This review aims to provide an overview of some advanced
      technologies employed for bioactive extraction, as well as the bioactives
      incorporation into protein formulations to produce biomaterials and food
      packaging.

PMID- 30201560
TI  - Enhanced B-phycoerythrin production by the red microalga Porphyridium marinum: A
      powerful agent in industrial applications.
AB  - The production of B-phycoerythrin (B-PE) from the red microalga Porphyridium
      marinum was optimized before to purify it and subsequently study its antioxidant
      activities. NaNO3, K2HPO4 and metal traces concentrations of the culture medium,
      and luminosity parameters were chosen, according to the Plackett-Burman design,
      as the most influent factors on the B-PE production by P. marinum. The
      optimization of these factors according to the Box-Behnken plan gave a maximum of
      B-PE production equal to 40 mg/g dry weight under the following conditions: NaNO3
      = 3.4 g/L; K2HPO4 = 0 g/L; light intensity = 70 MUmol photons/m2/s and metal
      solution = 1.5 mL/L. The B-PE also showed an interesting capacity to chelate Fe3+
      (IC50 = 13.91 +/- 0.21 MUg/mL) and a significant reducing power (OD700nm = 0.485
      +/- 0.011 at 100 MUg/mL). The present study reports the antioxidant potential of
      purified B-PE from P. marinum that could be potentially used as a source of
      bioactive protein for a wide range of cosmetic and pharmaceutical applications.

PMID- 30201561
TI  - Magnetic nanoparticles as versatile carriers for enzymes immobilization: A
      review.
AB  - Enzymes are highly efficient biocatalysts and widely employed in biotechnological
      sectors. However, lack of (re)-purification and efficient recovery of enzymes are
      among the most critical and challenging aspects, which render them enormously
      expensive for industrial exploitability. Aiming to tackle these challenges,
      magnetic nanoparticles (MNPs) have gained a special place as versatile carriers
      and supporting matrices for immobilization purposes, owing to the exceptional
      properties of MNPs, such as large surface area, large surface-to-volume ratio,
      and mobility and high mass transference. More importantly, they can also be
      easily separated and recovered by applying an external magnetic field. Apart from
      their biocompatible micro-environment, the utilization of such MNPs represents a
      noteworthy green chemistry approach, since it lengthens the biocatalyst lifetime
      through multiple recovery cycles. According to the literature evidence, various
      modification and/or functionalization approaches have been developed to produce
      MNPs for the effective immobilization of a broad variety of industrially
      important enzymes and biomolecules with improved characteristics. Enzymes
      immobilized on MNPs displayed a wide-working pH and temperature range, as well
      as, improved thermal and storage stabilities than that of their pristine
      counterparts. Co-immobilization of multi-enzymes could also be accomplished
      through nanoparticle-based approaches. This review presents an updated outlook on
      the development and characterization of MNPs, in particular, iron-based MNPs
      derived nano-constructs as support materials for enzyme immobilization.

PMID- 30201562
TI  - Gene immobilization on alginate/polycaprolactone fibers through electrophoretic
      deposition to promote in situ transfection efficiency and biocompatibility.
AB  - Alginate and polycaprolactone (PCL) were coelectrospun as composite nanofibers
      for in situ transfection, in which anionic alginate fibers were used to adsorb
      polyethyleneimine (PEI)/DNA polyplexes and biocompatible PCL fibers were applied
      to promote cell adhesion. To improve gene immobilization, direct-current electric
      field (DCEF) was applied to guide cationic polyplexes toward nanofibers on
      cathode. Fluorescent labeling experiments suggested that the applied DCEF not
      only accelerated but also increased the saturation levels of gene immobilization.
      Interestingly, these DCEF also increased the degradation of nanofibers. The water
      contact angle and Fourier-transform infrared spectrometry results indicated that
      the degraded component was mainly alginate. It suggested that the DCEF treatment
      may cause the electrophoresis of calcium ions to destabilize alginates fibers,
      and thus the degradation rates increased with the applied voltages. This alginate
      degradation increased the ratio of PCL in composite fibers, so the cell adhesion,
      viability, and proliferation were improved. Finally, these DCEF-treated fibers
      were used for substrate-mediated gene delivery. The transfection efficiency
      highly increased with DCEF when the voltages were lower than 1.5 V. This dynamic
      scaffold system not only provided a suitable microenvironment for cell ingrowth,
      but also improved gene immobilization and transfection, and thus promised its
      therapeutic effect for tissue regeneration.

PMID- 30201563
TI  - Karaya gum-graft-poly(2-(dimethylamino)ethyl methacrylate) gel: An efficient
      adsorbent for removal of ionic dyes from water.
AB  - In the present study, a novel hydrogel based on the polysaccharide, 'Karaya gum'
      has been synthesised by graft copolymerization and evaluated as an adsorbent for
      the removal of ionic dyes from aqueous solution. The hydrogel was made by
      simultaneous grafting and cross linking of Karaya gum using 2
      (dimethylamino)ethyl methacrylate (DMAEMA) and N,N'-methylene-bis-acrylamide via
      microwave irradiation. The graft copolymer gel was characterized by FTIR, TGA,
      SEM techniques. The swelling of the gel studied in buffer media of varying pH
      revealed a pH responsive behaviour with a maximum swelling in neutral pH and a
      minimum swelling at pH 1.2. The temperature dependent swelling study indicated 40
      degrees C as the lowest critical solution temperature. Kinetic studies indicated
      the swelling to be a second order process with Fickian diffusion as the water
      transport mechanism. The adsorption studies indicated maximum adsorption capacity
      of 89.28 and 101.42 mg/g towards methylene blue and indigo carmine respectively.
      The dye adsorption data is found to fit well with pseudo- second order kinetic
      model and the Freundlich adsorption isotherm model. The adsorption was found to
      be a multistep process with surface adsorption followed by intraparticle
      diffusion. Thermodynamic studies revealed the adsorption of dyes to be
      spontaneous.

PMID- 30201564
TI  - N,N,N-trimethyl chitosan modified flaxseed oil based mucoadhesive
      neuronanoemulsions for direct nose to brain drug delivery.
AB  - Here we fabricated flaxseed oil-based neuronanoemulsions (NNEs) which were
      further surface-modified with a mucoadhesive polymer, N,N,N-trimethyl chitosan
      (TMC) to form mucoadhesive neuronanoemulsions (mNNEs). The NNEs were loaded with
      high partitioning ropinirole-dextran sulfate (ROPI-DS) nanoplex and fabricated
      using hot high-pressure homogenization (HPH) technique. NNEs were optimized using
      Central Composite experimental design. TMC modified mNNE have not been prepared
      yet for direct nose to brain drug delivery. Here, an objective to provide
      controlled drug release with prolonged residence on the nasal mucosa for the
      treatment of Parkinson's disease (PD) is at prime consideration. Enhanced brain
      targeting through BBB bypass drug delivery, improved therapeutic efficacy through
      enhanced retention of mNNE formulation over nasal mucosal membrane, reduced dose
      and frequency of administration, and safety were further expected outcomes of
      this experiment. The mNNE formulation was subjected to 6 month stability
      assessment. The mNNE formulation was administered to the Swiss albino mice model
      via intranasal route and both, the plasma and brain pharmacokinetics were
      estimated. The in vivo studies performed on mice exhibited high brain targeting
      efficiency of mNNE formulation through nose to brain delivery via olfactory
      pathway. The prepared intranasal mNNEs could be on the clinics, if investigated
      more for behavioral and neurotoxicity studies.

PMID- 30201565
TI  - Mineralized calcium carbonate/xanthan gum microspheres for lysozyme adsorption.
AB  - Calcium carbonate/xanthan gum (Ca2CO3/XG) microspheres were prepared using
      biomimetic mineralization method for lysozyme (Ly) adsorption. The morphology of
      Ca2CO3/XG microspheres was characterized by field emission scanning electron
      microscope (FE-SEM). The Ly adsorption behavior was verified by Fourier transform
      infrared (FTIR) and in situ fluorescence microscope images. The effects of pHs on
      lysozyme adsorption were investigated as well. It was revealed that CaCO3/XG
      microspheres could immobilize lysozyme efficiently via electrostatic interactions
      with adsorption rate and adsorption quantity of 58.55 +/- 0.56% and 18.7 +/- 1.2
      MUg/mg as the pH was 7.0. Comparatively, the values markedly improved to 80.97 +/
      0.15% and 24.3 +/- 0.1 MUg/mg respectively as the pH was 9.0 (p < 0.05).
      Additionally, UV and fluorescence spectrum showed that Ly maintained its original
      secondary structure during the adsorption/desorption process. The study therefore
      demonstrated that CaCO3/XG microspheres can be used as a practical and efficient
      support for Ly adsorption and desorption.

PMID- 30201566
TI  - Structure relationship of non-covalent interactions between phenolic acids and
      arabinan-rich pectic polysaccharides from rapeseed meal.
AB  - Covalent and non-covalent interactions between polyphenols and polysaccharides
      produced vital consequences on the sensory and nutritive qualities of the many
      foods. In the present study, the structure dependence of the non-covalent
      interactions between phenolic acids (PAs) and an arabinan-rich pectic
      polysaccharide from rapeseed meal (ARPP) was explored. Native RAPP and its
      hydrolysates as well as twenty-seven structurally diversified PAs were applied.
      The interaction was determined as the micrograms of PAs adsorbed by per milligram
      of polysaccharides (Qe, MUg/mg). On one hand, the molecular weight (Mw) of ARPP
      displayed a significant effect on the Qe of ferulic acid and a highest value
      (412.28 MUg/mg) was obtained for the ARPP hydrolysate having a Mw of 76 kDa. On
      the other hand, the substituent profile of PAs greatly affected their Qe values
      onto ARPP, although the results are monomer and substituent specific.
      Specifically, in terms of Qe, hydroxylation favored the interaction by 35.78% to
      271.22%, while methylation and esterification weakened the absorption by 44.78%
      to 230.71% and 16.48% to 78.68%, respectively. The case of esterification is more
      complicated that the attachment of OCH3 at 3-position (-26.14% to -77.04%) is
      adverse but that at 5-position is highly favorable (156.96% to 190.70%) for the
      interactions.

PMID- 30201567
TI  - A Zfp609 circular RNA regulates myoblast differentiation by sponging miR-194-5p.
AB  - Skeletal muscle development and growth regulatory mechanism is the focus of both
      animal genetics and medicine. The recent studies indicate that covalently closed
      circular RNAs (circRNAs) also play important role on muscle development through
      sequestering specific miRNAs. The present study was conducted to determine the
      functional roles of circZfp609, a recently identified circRNA, in the regulation
      of myogenesis in mouse myoblast cell line (C2C12). circZfp609 is predicted to has
      binding sites of miR-194-5p. circZfp609 knockdown increased the expression of
      Myf5 and MyoG, which indicated that circZfp609 suppressed myogenic
      differentiation. Via a luciferase screening assay, circZfp609 is observed to
      sponge to miR-194-5p with four potential binding sites. Specifically, we show
      that circZfp609 can sponge miR-194-5p to sequester its inhibition on BCLAF1 so as
      to repress the myogenic differentiation. Modulation of circZfp609 expression in
      muscle tissue may emerge as a potential target in breeding strategies attempting
      to control muscle development.

PMID- 30201568
TI  - Fabrication of polylactic acid/carbon nanotubes/chitosan composite fibers by
      electrospinning for strawberry preservation.
AB  - In this study, we employed electrospinning to fabricate polylactic acid
      (PLA)/carbon nanotubes (CNTs)/chitosan (CS) composite fibers containing different
      CS contents and examined the ability of these fibers for strawberry preservation
      for the first time. The experimental results showed that as CS content increased,
      the mechanical properties, solubility, and swelling ratio of the fiber films
      first improved and then degraded, with peak values being achieved at a CS content
      of 7 wt%. The antimicrobial activity test results showed that as CS content
      increased, the antimicrobial activity of the composite fiber films against four
      microorganisms increased and the activity was the best when the CS content was 7
      wt%. In addition, the composite fibers exhibited better antimicrobial activity
      against Gram-negative and -positive bacteria than against molds. Moreover, the
      fibers exhibited better antimicrobial activity against Staphylococcus aureus than
      against Escherichia coli. The preservation experiments showed that the
      nanocomposite fibers containing different CS contents exhibited good preservation
      effects for strawberries, with the fiber containing 7 wt% CS showing the best
      results. Thus, these fibers can delay the physiological changes in strawberries
      and extend their shelf life and therefore have important potential applications
      for fruit and vegetable preservation in the future.

PMID- 30201569
TI  - Comparative study on disintegration methods for oral film preparations.
AB  - Orodispersible films (ODFs) provide high application comfort due to rapid
      disintegration in the oral cavity. They increasingly found the approval of
      pharmaceutical research and development and were added to the European
      Pharmacopeia in 2012. The European Pharmacopeia explicitly demands disintegration
      testing for ODFs, but does not refer to a suitable method. The aim of this study
      was to collect and evaluate existing disintegration methods regarding their
      suitability to investigate different ODF formulations. Therefore, 21 ODF
      formulations produced at different gap heights and/or different amounts of
      suspended microcrystalline cellulose (MCC) particles were manufactured by solvent
      casting technique, using hypromellose (HPMC) as film-forming polymer. Four
      disintegration methods described in literature were applied to characterize the
      disintegration behavior of these formulations. They were the petri dish, the
      slide frame, slide frame and ball (SFaB) method as well as the PharmaTest(r)
      disintegration tester equipped with a film sample holder. All methods show
      similar tendencies, at which the disintegration time proportionally increases
      with increasing dry film thicknesses. Reduced disintegration times were observed
      for ODFs containing insoluble MCC particles compared to their corresponding
      particle-free formulations. However, the suitability to investigate varying types
      of ODFs applying the four different test methods highly depends on the intended
      purpose. Therefore, the slide frame and SFaB method seems to be particularly
      applicable for research and development purposes, whereas the PharmaTest(r)
      disintegration tester and the SFaB method fulfil the demands required for testing
      methods within the quality control.

PMID- 30201570
TI  - Crystallizing amino acids as bulking agents in freeze-drying.
AB  - Bulking agents as mannitol (Man) and glycine (Gly) require high bulking agent to
      stabilizer ratios to ensure their crystallization during the freeze-drying
      process. The aim of this study was to investigate several amino acids (AA) as
      potential alternative bulking agents in low AA to sucrose (Suc) ratios. A fast
      freeze-drying process was performed above the collapse temperature (Tc) of the
      amorphous phase challenging the crystalline AA scaffold. Lyophilizates and liquid
      formulations were characterized by differential scanning calorimetry. Karl
      Fischer titration and X-ray powder diffraction as well as macroscopic cake
      appearance and reconstitution times were evaluated. Stability of a monoclonal
      antibody was investigated by UV-Vis spectroscopy, light obscuration and size
      exclusion chromatography. Phenylalanine (Phe), leucine (Leu) and isoleucine (Ile)
      crystallized upon freeze-drying at 5/45 and 10/40 AA/Suc ratios. 2.5/47.5 AA/Suc
      ratio showed less pronounced crystallization. Crystallization peaks were not
      suppressed by 2 or 50 mg/mL antibody in Leu and Ile lyophilizates. Reconstitution
      times could be improved by addition of surfactant. No signs of protein
      aggregation were detected after freeze-drying. Man and Gly yielded inacceptable
      cake appearance when dried with the fast freeze-drying cycle in such low bulking
      agent to Suc ratios. Leu, Ile and Phe can be used as alternate bulking agents at
      lower bulking agent to Suc ratios compared to Man or Gly. The selected AAs
      provided promising cake characteristics and good protein process stability.

PMID- 30201571
TI  - Mycoplasma-Induced Toxic Epidermal Necrolysis with Severe Mucositis.

PMID- 30201572
TI  - Does the addition of earplugs improve adherence to a reduced eating rate
      protocol?
AB  - Eating slowly has been associated with low body mass and greater cephalic phase
      response. This study hypothesised that the novel addition of earplugs -that block
      the ear canal-to a previously developed slow eating protocol would increase
      postprandial satiety. 12 healthy young participants [(6 M, 6F) mean age (+/- SD)
      24.58 +/- 6.64 years, mean BMI 22.23 +/- 3.13 kg/m2] were randomised to a one way
      crossover study. Following anthropometric measurements an isocaloric meal was
      consumed and participants' normal eating rates (NER) were recorded. Participants
      received instruction on a slow eating rate protocol on 2 occasions with (SERIn)
      and without (SER-Out) earplugs. Perceived satiety was measured at the start of
      the meal, t = 0 and then at 15, 30, 45, 60, 90 and 120 min. Total area under the
      curve (TAUC) was calculated from visual analogue data to compare the different
      eating conditions. Perceived hunger (p = 0.034) and desire to eat (p = 0.005)
      were significantly lower and perceived fullness significantly greater (p = 0.03)
      in SER-In compared to NER, with no significant differences between SER-In and SER
      Out. Although there was a positive effect on perceived satiety for the SER-In
      group only, this study showed that there is no added effect in perceived
      satiation when earplugs are combined with a SER protocol.

PMID- 30201573
TI  - Non-pharmacological induction of rat 50 kHz ultrasonic vocalization: Social and
      non-social contexts differentially induce 50 kHz call subtypes.
AB  - The emission of 50 kHz ultrasonic vocalizations (USVs) by rats is thought to
      represent a measurable expression of the individuals underlying emotional state.
      These calls are also posited as fulfilling important communicative functions
      among conspecifics. In addition to social situations, 50 kHz USVs are recorded in
      a variety of reward-related contexts including sugary foods and drink, consumable
      ethanol, and drugs of abuse. The current study sought to directly compare several
      of these behavioural contexts in their capability to induce and modulate 50 kHz
      USV emission in adult male rats. Using two social conditions (exposure of naive
      rat to a naturally cycling female and reuniting with a same-sex cage partner) and
      two non-social conditions (access to consumables as Fruit Loops or 2% ethanol
      v/v), we analyzed USVs recorded in 6 stimulus-presentation sessions. Only the
      female-exposure condition was found to increase 50 kHz call rate significantly
      over baseline, and this induction sensitized across 4 standard recording
      sessions. The use of a same-sex cage-mate and the two consumable food rewards did
      not elicit higher than baseline 50 kHz calling. None of the behavioural contexts
      altered the acoustic parameters (peak frequency, duration, and bandwidth) of
      emitted 50 kHz calls. In counter-balanced recording sessions, calling across all
      groups was significantly reduced by pre-treatment with the dopamine antagonist
      haloperidol compared with vehicle. Non-social conditions appeared to induce a
      greater proportion of flat calls at the expense of non-trill FM calls, while the
      reverse was seen for social conditions. However, the type of food reward and the
      type of social context mattered for proportion of flat and trill calls
      respectively. When compared with a control, access to sugary food but not ethanol
      induced a greater proportion of flat calls, and the female but not the cage-mate
      stimulus induced a greater proportion of trill calls.

PMID- 30201574
TI  - The neuropathological investigation of the brain in a monkey model of autism
      spectrum disorder with ABCA13 deletion.
AB  - The precise biological etiology of autism spectrum disorder (ASD) remains
      unknown. In this study, we investigated the neuropathology of a monkey model of
      autism Human ABCA13 is the largest ABC transporter protein, with a length of 5058
      amino acids and a predicted molecular weight of >450 kDa. However, the function
      of this protein remains to be elucidated. This protein is thought to be
      associated with major psychiatric disease. Using this monkey model of autism with
      an ABCA13 deletion and a mutation of 5HT2c, we neuropathologically investigated
      the changes in the neuronal formation in the frontal cortex. As a result, the
      neuronal formation in the cortex was found to be disorganized with regard to the
      neuronal size and laminal distribution in the ABCA13 deletion monkey. The
      catecholaminergic and GABAergic neuronal systems, serotoninergic neuronal
      formation (5HT2c) were also found to be impaired by an immunohistochemical
      evaluation. This study suggested that ABCA13 deficit induces the impairment of
      neuronal maturation or migration, and the function of the neuronal network. This
      protein might thus play a role in the neurodevelopmental function of the central
      nervous system and the dysfunction of this protein may be a pathophysiological
      cause of mental disorders including autism.

PMID- 30201575
TI  - Minimally Invasive Trigeminal Ablation: Transoral Approach for Targeting V2.
AB  - BACKGROUND: Trigeminal neuralgia (TN) is a chronic orofacial pain syndrome, which
      manifests as severe pain in the distribution of any trigeminal nerve branch.
      Though traditionally responsive to anticonvulsant therapy, TN can become
      refractory to medications and require surgical intervention. CASE DESCRIPTION: We
      present a case of V2 TN that was treated with minimally invasive trigeminal
      ablation. The patient presented with a 6-year history of type 1 TN and had failed
      the maximum tolerated doses of carbamazepine and gabapentin. There was no
      evidence of vascular compression on neuroimaging. After the patient refused
      stereotactic radiosurgery, she was offered minimally invasive trigeminal
      ablation. At 5 months postoperatively the patient reported complete alleviation
      of pain with tolerable sensorineural numbness. CONCLUSIONS: The endoscopic
      approach allows for precise targeting of V2, which is ideal in patients
      undergoing targeted neuroablation for pain. This is the first documented case of
      a transoral endoscopic approach toward ablative V2 TN management.

PMID- 30201576
TI  - Role of Endoscopy in Resection of Intracanalicular Vestibular Schwannoma via
      Middle Fossa Approach: Technical Nuances.
AB  - BACKGROUND: Surgical resection of vestibular schwannomas (VS) located within the
      internal auditory canal (IAC) is challenging, especially those located very
      laterally in the IAC. Various transcranial approaches have been described for
      resection of intracanalicular VS including retrosigmoid, translabyrinthine, and
      middle fossa approaches. Each approach has its indications, advantages, and
      limitations. The middle fossa approach (MFA) is considered by many authors as the
      gold standard approach for resection of small intracanalicular VS in young
      patients with serviceable hearing; however, there is often a limitation in
      complete visualization of the tumor. METHODS: The authors present an illustrative
      case to highlight the technical nuances of complementary use of endoscopy in MFA
      for complete resection of intracanalicular VS located at the IAC fundus,
      preserving preoperative hearing status and mainting intact facial nerve function.
      RESULTS: In our experience, the combined use of the endoscope and the microspe as
      described here and illustrated in our case, improves visualization of the IAC and
      its contents, improving ressection and outcomes. CONCLUSIONS: MFA allows for a
      direct yet safe surgical corridor to small intracanalicular VS. The
      implementation of endoscopy with MFA, especially for VS located laterally in the
      IAC, allows for better opportunity for complete resection of the tumor with
      improved preservation of hearing and facial nerve function.

PMID- 30201577
TI  - Large Scalp Defect Repair with Flap Reconstruction Using Tissue Expander After
      Combined Bypass in Case of Moyamoya Disease.
AB  - BACKGROUND: Combined revascularization is the preferred surgical management of
      adult Moyamoya disease. However, postoperative flap necrosis of the scalp is not
      an uncommon complication. We investigated the role of scalp incision design on
      the basis of the course of the superficial temporal artery (STA) to prevent
      postoperative scalp necrosis. The utility of tissue expander in wide scalp defect
      repair is explored. CASE DESCRIPTION: A 13-year-old female patient underwent STA
      to-middle cerebral artery anastomosis and encephaloduroarteriosynangiosis due to
      ischemic symptoms. However, she suffered from wide scalp necrosis measuring 10.5
      * 10 cm after bypass surgery. Conventional rotational scalp flap reconstruction
      was impossible due to the wide defect, and therefore split thickness skin graft
      was considered. However, aesthetic compromise or hair loss is a psychologic
      burden in an adolescent female. Two tissue expanders were inserted under the
      contralateral normal scalp, and a gradual expansion was achieved by saline
      infusion for 3 months. Finally, a wide scalp flap, which covered the large
      defect, was obtained using this procedure. The patient underwent rotational flap
      advancement and was discharged without any hair loss wound. CONCLUSIONS:
      Miserable scalp flap design results in a large scalp defect during combined
      bypass surgery. However, tissue expanders aided the reconstruction of a large
      scalp defect. Reconstruction using tissue expanders and advancement of local
      rotation flap is recommended in case of large scalp necrosis. The procedure
      yields cosmetically superior outcomes due to scalp hair conservation and
      concealment of postoperative scar behind the hair line.

PMID- 30201578
TI  - Combining Investigation of Imaging Markers (Island Sign and Blend Sign) and
      Clinical Factors in Predicting Hematoma Expansion of Intracerebral Hemorrhage in
      the Basal Ganglia.
AB  - BACKGROUND AND OBJECTIVE: Intracerebral hemorrhage (ICH) is the most difficult-to
      treat form of stroke and accounts for about 10%-30% of all strokes worldwide.
      Hematoma expansion (HE), which occurs in one third of patients with ICH, is
      strongly predictive of worse prognosis and potentially preventable if high-risk
      patients are identified in the early phase of ICH. We summarized data from recent
      studies on HE prediction and classified those potential indicators into 2
      categories: 1) clinical and laboratory and 2) radiographic. Therefore, we aimed
      to identify the accuracy of L, that is, the value of combining predictors in
      predicting HE of ICH in basal ganglia. METHODS: We retrospectively investigated
      the clinical database of Qinghai Provincial People's Hospital for patients with
      ICH aged >18 years between January 2015 and January 2018. As inclusion criteria,
      we defined 1) ICH diagnosed on noncontrast computed tomography (CT); 2)
      noncontrast CT performed on enrollment within 6 hours after onset of symptoms; 3)
      follow-up CT scan performed within 24 hours after the baseline CT scan; and 4)
      all of the primary hematoma was located in the basal ganglia. Univariate and
      multivariate logistic regression analysis were used to analyze the potential HE
      predictors, and then receiver operating characteristic curves were used to
      evaluate the L (the value of combining predictors) of imaging markers and
      clinical factors in predicting HE. RESULTS: Of the 99 patients with HE, island
      sign was present in 48.48% (48/99) of patients and blend sign was present in
      34.34% (34/99) of patients. Multivariate logistic regression analysis identified
      time to baseline CT scan (odds ratio [OR] 1.574; 95% confidence interval [CI]
      1.205-2.054; P = 0.001), baseline hematoma volume (P = 0.001), presence of island
      sign (OR 11.247; 95% CI 4.701-26.909; P = 0.000), presence of blend sign (OR
      3.104; 95% CI 1.425-6.765; P = 0.004), anticoagulants use or international
      normalized ratio >1.5 (OR 2.755; 95% CI 1.072-7.082; P = 0.035), and
      intraventricular hemorrhage (OR 2.351; 95% CI 1.066-5.187; P = 0.034) as
      independent predictors of HE. The sensitivity and specificity of L (value of
      combining predictors) were 88.89% and 80.84%, respectively; the area under the
      curve was 0.918. CONCLUSIONS: The findings indicated that the ability of L to
      predict HE was much more excellent than these 6 predictors alone. L showed a high
      association with HE, with an accuracy of 91.8%, and was a reliable value of
      combining predictors in terms of predicting HE. L may serve as a promising,
      noninvasive tool for clinical therapeutic strategy.

PMID- 30201579
TI  - Multiple Intracranial Aneurysms from Coccidioidal Meningitis: A Case Report
      Featuring Aneurysm Formation and Spontaneous Thrombosis with Literature Review.
AB  - BACKGROUND: Coccidioidal meningitis can progress to vasculitis with aneurysm
      formation. Although aneurysmogenesis is rare, it carries exceptionally high
      mortality. Except in one instance, prior case reports have documented universally
      fatal consequences. CASE DESCRIPTION: A 26-year-old man developed disseminated
      coccidioidomycosis with formation of multiple aneurysms throughout the anterior
      intracranial vasculature bilaterally. This report is unique in that it chronicles
      the formation and subsequent spontaneous thrombosis of several aneurysms over a 4
      week period. In total ten aneurysms were documented in the same patient-the
      highest reported to date. The patient was eventually discharged from the hospital
      for what has heretofore been a universally fatal disease process. Neurologic
      examination and vascular imaging one month after discharge demonstrated stable
      findings. CONCLUSIONS: Coccidioidal aneurysms carry a high mortality. The
      mainstay of therapy remains lifelong triazole antifungal therapy with the
      addition of liposomal amphotericin in cases of treatment failure. Steroid use is
      controversial but should be considered whenever there is vascular involvement.
      Although watchful waiting is reasonable in light of the possibility of
      spontaneous thrombosis with medical management, dynamic changes in aneurysm size
      or configuration should prompt timely endovascular or operative interventions.

PMID- 30201580
TI  - Reduction of Slippage Influences Surgical Outcomes of Grade II and III Lumbar
      Isthmic Spondylolisthesis.
AB  - OBJECTIVE: To explore influence of reduction of slippage on radiologic
      parameters, clinical outcomes, and perioperative complications in treatment of
      grade II/III lumbar isthmic spondylolisthesis. METHODS: We divided 156 patients
      with grade II/III spondylolisthesis into 2 groups with preoperative balanced or
      unbalanced pelvis. We further divided each group into group A with postoperative
      grade I or less slippage and group B with persistent grade II/III slippage
      postoperatively. Outcome scores were measured for clinical evaluation. Radiologic
      parameters included pelvic incidence, sacral slope, pelvic tilt, and lumbar
      lordosis. RESULTS: In group A patients with preoperative balanced pelvis, lumbar
      lordosis significantly decreased from 60.2 degrees  +/- 10.6 degrees  to 50.9
      degrees  +/- 9.8 degrees  after operation (P < 0.05). In group A patients with
      preoperative unbalanced pelvis, pelvic tilt decreased from 29.1 degrees  +/- 8.6
      degrees  to 24.1 degrees  +/- 9.1 degrees , and sacral slope increased from 36.1
      degrees  +/- 9.0 degrees  to 41.3 degrees  +/- 8.4 degrees , significantly (P <
      0.05). There were significant differences (P < 0.05) between group A and B in
      postoperative visual analog scale for low back pain (1.5 +/- 0.8 vs. 2.1 +/-
      0.9), Oswestry Disability Index (13.8 +/- 8.7 vs. 18.1 +/- 7.6), and EuroQol-5
      dimensions (0.75 +/- 0.14 vs. 0.68 +/- 0.11) scores in patients with preoperative
      unbalanced pelvis. CONCLUSIONS: In patients with grade II/III lumbar isthmic
      spondylolisthesis, if postoperative slippage was grade I or less, pelvic tilt and
      sacral slope could be corrected more effectively, and better clinical outcomes
      would be obtained for cases with preoperative unbalanced pelvis. In cases with
      balanced pelvis, lumbar lordosis could be better corrected by the same degree of
      reduction, although clinical outcomes would not be influenced significantly.
      Perioperative complications would not be influenced by reduction of slippage.

PMID- 30201581
TI  - Quantitative Assessment of In-Stent Stenosis After Pipeline Embolization Device
      Treatment of Intracranial Aneurysms: A Single-Institution Series and Systematic
      Review.
AB  - BACKGROUND: Very little is known about the incidence of in-stent stenosis after
      flow diverter treatment of intracranial aneurysms. We sought to evaluate the
      incidence and clinical significance of in-stent stenosis at angiographic follow
      up after Pipeline embolization device (PED) placement using quantitative
      measures. METHODS: The clinical and radiological records from all patients
      undergoing PED treatment of intracranial aneurysms at a major U.S. academic
      center from March 2013 to July 2017 were retrospectively reviewed. A modified
      version of the North American Symptomatic Carotid Endarterectomy criteria was
      used to quantify the degree of stenosis on the most recent postprocedural
      angiogram. The percentage of stenosis was calculated as 1 - (narrowest vessel
      diameter/maximal midstent diameter within the artery) at the first follow-up
      angiogram. The PubMed, Web of Science, and EMBASE databases were additionally
      searched from inception until April 2018 for the rates of in-stent stenosis after
      flow diversion. RESULTS: A total of 155 patients (mean age, 58.3 years; 30 males)
      with 162 aneurysms underwent treatment with the PED at our institution. In-stent
      stenosis was detected in 12 patients (7.1%) at 6 months. The mean percentage of
      stenosis was 39.7%. All 12 patients remained asymptomatic, except for 1 who
      developed hemiplegia secondary to an unrelated ischemic stroke. The aneurysm
      occlusion rates at 6 months were comparable between the stenosis and nonstenosis
      cohorts (76.9% and 71.6%, respectively). Within the stenosis cohort, further
      follow-up angiograms after 6 months were available for 6 patients, of whom 3
      (50%) had either complete resolution or improvement. Of the 43 included studies,
      28 reported on the use of the PED, with 2448 patients. The mean reported rate of
      in-stent stenosis after PED placement was 8.8% (range, 0%-39%). CONCLUSIONS: In
      stent stenosis remains a rare complication of PED placement for intracranial
      aneurysms. When occurring, it appears to largely be self-limiting, with a benign
      clinical course.

PMID- 30201582
TI  - Emergent Single Burr Hole Evacuation for Traumatic Acute Subdural Hematoma with
      Cerebral Herniation: A Retrospective Cohort Comparison Analysis.
AB  - OBJECTIVE: To investigate the clinical benefits of emergent single burr hole
      evacuation technology in traumatic acute subdural hematoma (ASDH) with cerebral
      herniation cases. METHODS: We conducted a review comparing patients with ASDH
      with cerebral herniation who underwent single burr hole evacuation followed by
      decompressive craniectomy and intracranial hematoma removal surgery (n = 45,
      group A) and those who underwent decompressive craniectomy and intracranial
      hematoma removal surgery after rapid infusion of mannitol 250 mL (n = 53, group
      B) in our institution. Pre- and postoperative assessments included Glasgow Coma
      Scale (GCS), Glasgow Outcome Scale (GOS), activities of daily living (ADLs), and
      common complication incidences. RESULTS: At 1 and 6 months after operation, the
      median GCS score of group A was significantly higher than group B (P = 0.04 and P
      = 0.03, respectively). After 6 months, the GOS score and ADLs between the 2
      groups had significant differences (P < 0.05). There were no differences between
      the 2 groups in the common complication incidences. CONCLUSIONS: Emergent single
      burr hole evacuation in combination with decompressive craniectomy surgery is a
      useful treatment for ASDH with cerebral herniation, which can achieve reduction
      of intracranial pressure as soon as possible and improve the prognosis.

PMID- 30201583
TI  - Clinical Integration of Quantitative Susceptibility Mapping Magnetic Resonance
      Imaging into Neurosurgical Practice.
AB  - OBJECTIVE: To introduce quantitative susceptibility mapping (QSM), a novel
      magnetic resonance imaging sequence, to the field of neurosurgery. METHODS: QSM
      is introduced both in its historical context and by providing a brief overview of
      the physics behind the technique tailored to a neurosurgical audience. Its
      application to clinical neurosurgery is then highlighted using case examples.
      RESULTS: QSM offers a quantitative assessment of susceptibility (previously
      considered as an artifact) via a single, straightforward gradient echo
      acquisition. QSM differs from standard susceptibility weighted imaging in its
      ability to both quantify and precisely localize susceptibility effects. Clinical
      applications of QSM are wide reaching and include precise localization of the
      deep nuclei for deep brain stimulation electrode placement, differentiation
      between blood products and calcification within brain lesions, and enhanced
      sensitivity of cerebral micrometastasis identification. CONCLUSIONS: We present
      this diverse range of QSM's clinical applications to neurosurgical care via case
      examples. QSM can be obtained in all patients able to undergo magnetic resonance
      imaging and is easily integratable into busy neuroradiology programs because of
      its short acquisition time and straightforward, automated offline postprocessing
      workflow. Clinical integration of QSM may help clinicians better identify and
      characterize neurosurgical lesions, thereby improving patient care.

PMID- 30201584
TI  - Toxicity of the biocide polycarbamate, used for aquaculture nets, to some marine
      fish species.
AB  - We investigated toxic effects of the antifouling biocide polycarbamate (PC) on
      marine fish by conducting acute, early-life stage toxicity (ELS), and embryo
      toxicity tests. Mummichog (Fundulus heteroclitus) 96-h LC50 values for hatched
      larvae (body weight about 2.0 mg) and juveniles (660 +/- 36 mg) were about 12 and
      630 MUg/L, respectively. The ELS test using mummichog embryos yielded a lowest
      observed-effect concentration of 3.9 MUg/L and a no-observed-effect concentration
      of 2.1 MUg/L with growth as the most sensitive endpoint. The embryo toxicity test
      for spotted halibut (Verasper variegatus) revealed a 10-d EC50 of 8.1 MUg/L with
      abnormality as an endpoint. During the ELS and embryo toxicity tests,
      morphological abnormalities (notochord undulation) were induced in the embryos.
      Biochemical and gene-expression analysis suggest that PC-induced morphological
      abnormalities involve disruption of lysyl oxidase-mediated collagen fiber
      organization, essential for notochord formation, and inhibition of gene
      expression related to notochord formation.

PMID- 30201585
TI  - Rhinogenous optic neuritis with full recovery of vision - The role of endoscopic
      optic nerve decompression and a review of literature.
AB  - BACKGROUND: Optic neuritis resulting from paranasal sinusitis is an infrequently
      described but clinically important and treatable entity. The role of optic nerve
      decompression has been well established in atraumatic optic neuropathies which
      are compressive in origin. However, its role in optic neuritis and other
      infective or inflammatory processes is lacking, and the role for early surgical
      intervention remains controversial. CASE REPORT: In this case report, we describe
      a patient who presented with sudden onset of right vision loss secondary to optic
      neuritis from pansinusitis. He was treated with systemic antibiotics and steroids
      along with an urgent endoscopic sinus surgery with optic nerve decompression.
      Full restoration of his vision was recorded within 24 h of surgical
      decompression. CONCLUSION: Optic neuritis secondary to paranasal sinusitis is a
      clinically important entity and timely diagnosis and decompression is key to
      vision restoration.

PMID- 30201586
TI  - Distinct Characteristics and Metastatic Behaviors of Late Recurrence in Patients
      With Hormone Receptor-positive/Human Epidermal Growth Factor Receptor 2-negative
      Breast Cancer: A Single Institute Experience of More Than 10 Years.
AB  - INTRODUCTION: Patients with hormone receptor-positive and human epidermal growth
      factor receptor 2-negative (HR+/HER2-) breast cancer have a constant risk of
      relapse over time. Nearly one-half of the recurrences occur more than 5 years
      after diagnosis, described as late recurrence, but little is known about late
      recurrence. PATIENTS AND METHODS: We reviewed the clinical data of 1941 patients
      with HR+/HER2- breast cancer who had operations in the Cancer Institute and
      Hospital, Chinese Academy of Medical Sciences, during 2003 to 2009, and found 390
      relapsed cases. Among them, 281 patients were early recurrence, and 109 were late
      recurrence. RESULTS: In the late recurrence group, patients with <= 3 lymph node
      metastases, double HR+ (estrogen receptor-positive/progesterone receptor
      positive) were more common (72.48% vs. 55.52%; P = .005; 82.57% vs. 71.89%; P =
      .029, respectively) when compared with the early recurrence group. The lung
      seemed to be a preferential site of late recurrence. Although visceral disease
      and multi-organ metastases were more frequent in the late recurrence group,
      survival after recurrence was significantly longer than that in the early
      recurrence group (52 vs. 40 months; hazard ratio, 1.508; 95% confidence interval,
      1.142-1.992; P = .003). Moreover, progression-free survival of first-line
      treatment was an independent prognostic factor of survival after recurrence in
      the late recurrence group. CONCLUSION: Late recurrence differed from early
      recurrence in many ways in HR+/HER2- breast cancer, and its prognosis was much
      better. The lung may be a preferential site of late recurrence. More attention
      should be paid to late recurrence itself.

PMID- 30201587
TI  - Risk of bleeding and arterial cardiovascular events in patients with splanchnic
      vein thrombosis in Denmark: a population-based cohort study.
AB  - BACKGROUND: Little is known about adverse events following splanchnic vein
      thrombosis. Venous thromboembolism has been associated with increased risks of
      bleeding and arterial cardiovascular events. To learn more about the clinical
      course of splanchnic vein thrombosis, we examined the risks of bleeding and
      arterial cardiovascular events in patients with the disease, and compared them
      with the risks in patients with deep vein thrombosis (DVT) or pulmonary embolism
      (PE) and individuals from the general population. METHODS: In this population
      based cohort study, we used data for all patients with a diagnosis of splanchnic
      vein thrombosis recorded in the Danish National Patient Registry (DNPR) between
      Jan 1, 1994, and Nov 30, 2013 (cumulative source population 7 310 450
      individuals). We created two comparison cohorts using data from the DNPR and the
      Civil Registration System for the same period: one of patients with DVT or PE and
      another of individuals from the general population. Comparison cohorts (ten
      comparators per patient with splanchnic vein thrombosis) were matched on sex,
      age, and calendar year of diagnosis. We calculated absolute risks and used
      proportional hazard regression to calculate adjusted hazard ratios (HRs) for the
      primary outcomes of bleeding and arterial cardiovascular events after splanchnic
      vein thrombosis diagnosis (or the index date for comparison cohorts). FINDINGS:
      1915 patients with splanchnic vein thrombosis, 18 373 patients with DVT or PE,
      and 19 150 individuals from the general population were included in the study.
      Patients with splanchnic vein thrombosis were followed up for a median of 1 year
      (IQR 0.1-3.9). These patients had a high risk of bleeding in the 30 days after
      diagnosis, both in absolute terms (4.3% [95% CI 3.5-5.3]) and in adjusted models
      (HR 9.64 [95% CI 6.46-14.40] vs DVT or PE; 39.79 [19.44-81.46] vs general
      population). Bleeding risk was still significantly increased in patients with
      splanchnic vein thrombosis up to 1 year after diagnosis (HR 3.01 [95% CI 2.28
      3.97] vs DVT or PE; 6.83 [4.83-9.65] vs general population), and remained
      elevated for up to 10 years compared with patients with DVT or PE (1.93 [1.12
      3.34]) and for up to 19 years compared with the general population (5.90 [2.22
      15.64]). The risk of arterial cardiovascular events in patients with splanchnic
      vein thrombosis was high in the year after diagnosis (absolute risk 3.3% [95% CI
      2.6-4.2] up to 30 days; 7.0% [5.8-8.4] up to 31-365 days), and in adjusted models
      was significantly higher than in patients with DVT or PE (HR 7.05 [95% CI 4.74
      10.48] up to 30 days; 2.10 [1.62-2.72] up to 31-365 days) and individuals from
      the general population (15.75 [9.26-26.79] and 3.17 [2.34-4.27], respectively).
      However, this risk did not remain significantly elevated above that of patients
      with DVT or PE after 1 year or the general population after 5 years.
      INTERPRETATION: Patients with splanchnic vein thrombosis are at increased risk of
      adverse outcomes, particularly bleeding but also arterial cardiovascular events,
      for years after diagnosis compared with patients with DVT or PE and the general
      population. Physicians should be cognisant of these risks in patients with
      splanchnic vein thrombosis. FUNDING: The Program for Clinical Research
      Infrastructure (PROCRIN), established by the Lundbeck Foundation and the Novo
      Nordisk Foundation.

PMID- 30201588
TI  - Splanchnic vein thrombosis: what are the long-term risks?

PMID- 30201589
TI  - There's something in the air.
AB  - A 20-year-old woman presented with bilateral constant positive visual phenomenon
      since she was 9 years old. The symptoms had been worsening and becoming more
      intrusive in the last 3 years. Recently she has also had a migrainous episode.
      All ophthalmic and neurological investigations were normal. Her symptoms met the
      diagnostic criteria for visual snow. The diagnosis was explained, and the patient
      was reassured. Ophthalmologists and neurologists need to be aware of this
      condition to avoid over investigation and worsening of patient anxiety.

PMID- 30201590
TI  - Stable isotope labelling by amino acids in cell culture (SILAC) applied to
      quantitative proteomics of Edwardsiella tarda ATCC 15947 under prolonged cold
      stress.
AB  - Edwardsiella tarda poses a threat to human health and has resulted in enormous
      economic losses in aquaculture. Low temperatures are usually applied to contain
      the growth of this microorganism. In this study, stable isotope labelling by
      amino acids in cell culture (SILAC) was used to conduct comparative proteomic
      quantitation of E. tarda ATCC 15947 under cold stress for two weeks. We
      identified 1391 proteins, of which 898 were quantifiable. Of these, 72 proteins
      were upregulated and 164 were downregulated in response to cold stress. Even
      though E. tarda ATCC 15947 is not a psychrophile, several key proteins related to
      DNA synthesis and transcription were significantly upregulated. Additionally,
      proteins related to haemolytic activities and gluconeogenesis were upregulated,
      even though E. tarda ATCC 15497 is considered non-virulent in aquaculture. This
      study therefore delineated the specific proteomic response of this E. tarda ATCC
      15947 to prolonged cold stress.

PMID- 30201591
TI  - Pathogen-produced catalase affects immune priming: A potential pathogen strategy.
AB  - Immune priming in invertebrates occurs when the first contact with a
      pathogen/parasite enhances resistance after a second encounter with the same
      strain or species. Although the mechanisms are not well understood, there is
      evidence that priming the immune response of some hosts leads to greater pro
      oxidant production. Parasites, in turn, might counteract the host attack with
      antioxidants. Virulent pathogen strains may therefore mask invertebrate immune
      priming. For example, different parasite species overexpress catalase as a
      virulence factor to resist host pro-oxidants, possibly impairing the immune
      priming response. The aim of this study was firstly to evaluate the specificity
      of immune priming in Tenebrio molitor when facing homologous and heterologous
      challenges. Secondly, homologous challenges were carried out with two Metarhizium
      anisopliae strains (Ma10 and CAT). The more virulent strain (CAT) overexpresses
      catalase, an antioxidant that perhaps impairs a host immune response mediated by
      reactive oxygen species (ROS). Indeed, T. molitor larvae exhibited better immune
      priming (survival) in response to the Ma10 than CAT homologous challenge.
      Moreover, the administration of paraquat, an ROS-promoting agent, favoured
      survival of the host upon exposure to each fungal strain. We propose that some
      pathogens likely overcome pro-oxidant-mediated immune priming defences by
      producing antioxidants such as catalase.

PMID- 30201592
TI  - Dynamics of expression of antibacterial and antioxidant defence genes in Indian
      major carp, Labeo rohita in response to Aeromonas hydrophila infection.
AB  - Cells produce large number of antioxidant molecules to prevent reactive oxygen
      species-induced self-damage during microbial assault while generating
      simultaneously number of antimicrobial molecules to target the pathogen. The
      present study was aimed at looking into molecules involved in antibacterial and
      self-protection mechanism of a host Labeo rohita when challenged with a
      pathogenic bacterium Aeromonas hydrophila. Expression profiles of few of the
      important host antibacterial genes viz., inducible nitric oxide synthase (iNOS),
      lysozyme G (LysoG), apolipoprotein A-I (ApoA-I) and hepcidin, and self-defence
      anti-oxidant genes viz., manganese superoxide dismutase (MnSOD), catalase and
      glutathione peroxidases (GPx3) were examined in skin and muscle tissues of
      bacteria challenged fish. Transcription levels of iNOS, LysoG, ApoA-I, hepcidin,
      catalase, GPx3 and MnSOD were significantly upregulated (P < 0.05) in both
      tissues at different time points post-bacterial challenge. Increased expression
      of antibacterial genes in the muscle and skin clearly explains strong defensive
      mechanism activated in fish tissues in terms of both oxygen-dependent (iNOS) and
      independent (lysozyme) ways of microbe reduction, and bacterial lysis via
      production of antimicrobial molecules (ApoA-I and hepcidin) in the host.
      Simultaneous upregulation of MnSOD, GPx3 and catalase genes explains their
      involvement in patrolling the cells with regulated production of reactive oxygen
      species and keeping at a safe level to protect the host's own cells from
      oxidative damage.

PMID- 30201593
TI  - Selection and structural analysis of the NY25 peptide - A vaccine candidate from
      hemagglutinin of swine-origin Influenza H1N1.
AB  - The aim of this study was to construct a vaccine peptide candidate against
      pandemic Influenza H1N1 hemagglutinin and to test its structure. With the help of
      bioinformatic algorithms we showed that the sequence encoding the second
      polypeptide of pandemic Influenza H1N1 hemagglutinin (HA2) is protected from
      nonsynonymous mutations better than the sequence encoding its first polypeptide
      (HA1). With the help of secondary and ternary structure predicting algorithms we
      found the fragment of HA2 with the most reproducible secondary structure and
      synthesized the NY25 peptide corresponding to the residues Asn117 - Tyr141 of
      HA2. According to the circular dichroism spectra analysis, the peptide has short
      helix and beta hairpin. According to the analysis of differential fluorescence
      quenching results, two tyrosine residues are situated on a long distance from
      each other. These facts taken together with the positive results of affine
      chromatography with the serum of a person immunized by full-length hemagglutinin
      confirm that the structure of the fragment of viral full-length protein has been
      reproduced in the synthetic NY25 peptide. Amino acid sequence of the NY25 peptide
      (NLYEKVRSQLKNNAKEIGNGCFEFY) is relatively conserved in 18 subtypes of Influenza A
      virus hemagglutinin.

PMID- 30201594
TI  - Pancreatic Carcinoma Discovered by Sister Mary Joseph's Nodules.

PMID- 30201595
TI  - Gastric Kaposi Sarcoma.

PMID- 30201596
TI  - Double-Balloon Enteroscopy-Assisted Diagnosis of Malignancy Arising From Meckel's
      Diverticulum.

PMID- 30201597
TI  - Cost Effectiveness of Universal Screening for Hepatitis C Virus Infection in the
      Era of Direct-Acting, Pangenotypic Treatment Regimens.
AB  - BACKGROUND & AIMS: Most persons infected with hepatitis C virus (HCV) in the
      United States were born from 1945 through 1965; testing is recommended for this
      cohort. However, HCV incidence is increasing among younger persons in many parts
      of the country and treatment is recommended for all adults with HCV infection. We
      aimed to estimate the cost effectiveness of universal 1-time screening for HCV
      infection in all adults living in the United States and to determine the
      prevalence of HCV antibody above which HCV testing is cost effective. METHODS: We
      developed a Markov state transition model to estimate the effects of universal 1
      time screening of adults 18 years or older in the United States, compared with
      the current guideline-based strategy of screening adults born from 1945 through
      1965. We compared potential outcomes of 1-time universal screening of adults or
      birth cohort screening followed by antiviral treatment of those with HCV
      infection vs no screening. We measured effectiveness with quality-adjusted life
      years (QALY), and costs with 2017 US dollars. RESULTS: Based on our model,
      universal 1-time screening of US residents with a general population prevalence
      of HCV antibody greater than 0.07% cost less than $50,000/QALY compared with a
      strategy of no screening. Compared with 1-time birth cohort screening, universal
      1-time screening and treatment cost $11,378/QALY gained. Universal screening was
      cost effective compared with birth cohort screening when the prevalence of HCV
      antibody positivity was greater than 0.07% among adults not in the cohort born
      from 1945 through 1965. CONCLUSIONS: Using a Markov state transition model, we
      found a strategy of universal 1-time screening for chronic HCV infection to be
      cost effective compared with either no screening or birth cohort-based screening
      alone.

PMID- 30201598
TI  - Clonal evolution of acute myeloid leukemia with CEBPA double mutations after long
      term remission: case report and a literature review.

PMID- 30201599
TI  - Pediatric Deep Venous Thrombosis and Pulmonary Embolism: Can It Be
      Antiphospholipid Syndrome?

PMID- 30201600
TI  - eHealth Literacy in People Living with HIV: Systematic Review.
AB  - BACKGROUND: In the era of eHealth, eHealth literacy is emerging as a key concept
      to promote self-management of chronic conditions such as HIV. However, there is a
      paucity of research focused on eHealth literacy for people living with HIV (PLWH)
      as a means of improving their adherence to HIV care and health outcome.
      OBJECTIVE: The objective of this study was to critically appraise the types,
      scope, and nature of studies addressing eHealth literacy as a study variable in
      PLWH. METHODS: This systematic review used comprehensive database searches, such
      as PubMed, EMBASE, CINAHL, Web of Science, and Cochrane, to identify quantitative
      studies targeting PLWH published in English before May 2017 with eHealth literacy
      as a study variable. RESULTS: We identified 56 unique records, and 7 papers met
      the eligibility criteria. The types of study designs varied (descriptive, n=3;
      quasi-experimental, n=3; and experimental, n=1) and often involved community
      based settings (n=5), with sample sizes ranging from 18 to 895. In regards to
      instruments used, 3 studies measured eHealth literacy with validated instruments
      such as the eHealth Literacy Scale (eHEALS); 2 studies used full or short
      versions of Test of Functional Health Literacy in Adults, whereas the remaining 2
      studies used study-developed questions. The majority of studies included in the
      review reported high eHealth literacy among the samples. The associations between
      eHealth literacy and health outcomes in PLWH were not consistent. In the areas of
      HIV transmission risk, retention in care, treatment adherence, and virological
      suppression, the role of eHealth literacy is still not fully understood.
      Furthermore, the implications for future research are discussed. CONCLUSIONS:
      Understanding the role of eHealth literacy is an essential step to encourage PLWH
      to be actively engaged in their health care. Avenues to pursue in the role of
      eHealth literacy and PLWH should consider the development and use of standardized
      eHealth literacy definitions and measures.

PMID- 30201601
TI  - Smartphone-Based Contingency Management Intervention to Improve Pre-Exposure
      Prophylaxis Adherence: Pilot Trial.
AB  - BACKGROUND: Pre-exposure prophylaxis (PrEP) provides a strong preventative
      benefit to individuals at risk for HIV. While PrEP adherence is highly correlated
      with its efficacy, adherence rates are variable both across and within persons.
      OBJECTIVE: The objective of this study was to develop and pilot-test a smartphone
      based intervention, known as mSMART, that targets PrEP adherence. mSMART provides
      contingency management in the form of monetary incentives for daily PrEP
      adherence based on a real-time adherence assessment using a camera-based
      medication event-monitoring tool as well as medication reminders, PrEP education,
      individualized behavioral strategies to address PrEP adherence barriers, and
      medication adherence feedback. METHODS: This was a 4-week open-label, phase I
      trial in a community sample of young men who have sex with men already on PrEP
      (N=10). RESULTS: Although adherence composite scores corresponding to PrEP
      biomarkers indicated that 90% (9/10) of the sample already had an acceptable
      baseline adherence in the protective range, by the end of the 4-week period, the
      scores improved for 30% (3/10) of the sample-adherence did not worsen for any
      participants. Participants reported mean PrEP adherence rates of 91% via daily
      entries in mSMART. At the end of the 4-week period, participants indicated
      acceptable ratings of satisfaction, usability, and willingness to recommend
      mSMART to others. There were no technical difficulties associated with smartphone
      compatibility, user misunderstandings about mSMART features that interfered with
      daily use, or study attrition. CONCLUSIONS: This study is the first to apply
      contingency management to PrEP adherence. Findings indicated that mSMART is
      feasible and acceptable. Such an adherence intervention administered via a user
      friendly smartphone app can allow for widespread dissemination. Future efficacy
      trials are needed. TRIAL REGISTRATION: ClinicalTrials.gov NCT02895893;
      https://clinicaltrials.gov/ct2/show/NCT02895893 (Accessed by Webcite at
      http://www.webcitation.org/72JskjDJq).

PMID- 30201602
TI  - Using New and Innovative Technologies to Assess Clinical Stage in Early
      Intervention Youth Mental Health Services: Evaluation Study.
AB  - BACKGROUND: Globally there is increasing recognition that new strategies are
      required to reduce disability due to common mental health problems. As 75% of
      mental health and substance use disorders emerge during the teenage or early
      adulthood years, these strategies need to be readily accessible to young people.
      When considering how to provide such services at scale, new and innovative
      technologies show promise in augmenting traditional clinic-based services.
      OBJECTIVE: The aim of this study was to test new and innovative technologies to
      assess clinical stage in early intervention youth mental health services using a
      prototypic online system known as the Mental Health eClinic (MHeC). METHODS: The
      online assessment within the MHeC was compared directly against traditional
      clinician assessment within 2 Sydney-based youth-specific mental health services
      (headspace Camperdown and headspace Campbelltown). A total of 204 young people
      were recruited to the study. Eligible participants completed both face-to-face
      and online assessments, which were randomly allocated and counterbalanced at a 1
      to-3 ratio. These assessments were (1) a traditional 45- to 60-minute headspace
      face-to-face assessment performed by a Youth Access Clinician and (2) an
      approximate 60-minute online assessment (including a self-report Web-based
      survey, immediate dashboard of results, and a video visit with a clinician). All
      assessments were completed within a 2-week timeframe from initial presentation.
      RESULTS: Of the 72 participants who completed the study, 71% (51/72) were female
      and the mean age was 20.4 years (aged 16 to 25 years); 68% (49/72) of
      participants were recruited from headspace Camperdown and the remaining 32%
      (23/72) from headspace Campbelltown. Interrater agreement of participants' stage,
      as determined after face-to-face assessment or online assessment, demonstrated
      fair agreement (kappa=.39, P<.001) with concordance in 68% of cases (49/72).
      Among the discordant cases, those who were allocated to a higher stage by online
      raters were more likely to report a past history of mental health disorders
      (P=.001), previous suicide planning (P=.002), and current cannabis misuse (P=.03)
      compared to those allocated to a lower stage. CONCLUSIONS: The MHeC presents a
      new and innovative method for determining key clinical service parameters. It has
      the potential to be adapted to varied settings in which young people are
      connected with traditional clinical services and assist in providing the right
      care at the right time.

PMID- 30201603
TI  - Defining Empowerment and Supporting Engagement Using Patient Views From the
      Citizen Health Information Portal: Qualitative Study.
AB  - BACKGROUND: The increasing presence of technology in health care has created new
      opportunities for patient engagement and with this, an intensified exploration of
      patient empowerment within the digital health context. While the use of
      technology, such as patient portals, has been positively received, a clear
      linkage between digital health solutions, patient empowerment, and health
      outcomes remains elusive. OBJECTIVE: The primary objective of this research was
      to explore the views of participants enrolled in an electronic health record
      portal access trial regarding the resultant influence of this technology on their
      feelings of patient empowerment. METHODS: The exploration of patient empowerment
      within a digital health context was done with participants in a tethered patient
      portal trial using interpretive description. Interpretive description is a
      qualitative methodology developed to pragmatically address clinical health
      questions. Patient demographics, self-reported health status, and self-identified
      technology adaptation contributed to the assessment of empowerment in this
      qualitative approach. RESULTS: This research produced a view of patient
      empowerment within the digital health context summarized in two overarching
      categories: (1) Being Heard and (2) Moving Forward. In each of these, two
      subcategories further delineate the aspects of empowerment, as viewed by these
      participants: Knowing More and Seeing What They See under Being Heard, and Owning
      Future Steps and Promoting Future Care under Moving Forward. This work also
      highlighted an ongoing interconnectedness between the concepts of patient
      empowerment, engagement, and activation and the need to further articulate the
      unique aspects of each of these. CONCLUSIONS: The results of this study
      contribute needed patient voice to the ongoing evolution of the concept of
      patient empowerment. In order to move toward more concrete and accurate measure
      of patient empowerment and engagement in digital health, there must be further
      consideration of what patients themselves identify as essential aspects of these
      complex concepts. This research has revealed relational and informational
      elements as two key areas of focus in the ongoing evolution of patient
      empowerment operationalization and measure.

PMID- 30201605
TI  - Hancock's digital revolution.

PMID- 30201604
TI  - Determining Physiological and Psychological Predictors of Time to Task Failure on
      a Virtual Reality Sorensen Test in Participants With and Without Recurrent Low
      Back Pain: Exploratory Study.
AB  - BACKGROUND: Sorensen trunk extension endurance test performance predicts the
      development of low back pain and is a strong discriminator of those with and
      without low back pain. Performance may greatly depend on psychological factors,
      such as kinesiophobia, self-efficacy, and motivation. Virtual reality video games
      have been used in people with low back pain to encourage physical activity that
      would otherwise be avoided out of fear of pain or harm. Accordingly, we developed
      a virtual reality video game to assess the influence of immersive gaming on the
      Sorensen test performance. OBJECTIVE: The objective of our study was to determine
      the physiological and psychological predictors of time to task failure (TTF) on a
      virtual reality Sorensen test in participants with and without a history of
      recurrent low back pain. METHODS: We recruited 24 individuals with a history of
      recurrent low back pain and 24 sex-, age-, and body mass index-matched
      individuals without a history of low back pain. Participants completed a series
      of psychological measures, including the Center for Epidemiological Studies
      Depression Scale, Pain Resilience Scale, Pain Catastrophizing Scale, Tampa Scale
      for Kinesiophobia, and a self-efficacy measure. The maximal isometric strength of
      trunk and hip extensors and TTF on a virtual reality Sorensen test were measured.
      Electromyography of the erector spinae, gluteus maximus, and biceps femoris was
      recorded during the strength and endurance trials. RESULTS: A two-way analysis of
      variance revealed no significant difference in TTF between groups (P=.99), but
      there was a trend for longer TTF in females on the virtual reality Sorensen test
      (P=.06). Linear regression analyses were performed to determine predictors of TTF
      in each group. In healthy participants, the normalized median power frequency
      slope of erector spinae (beta=.450, P=.01), biceps femoris (beta=.400, P=.01),
      and trunk mass (beta=-.32, P=.02) predicted TTF. In participants with recurrent
      low back pain, trunk mass (beta=-.67, P<.001), Tampa Scale for Kinesiophobia
      (beta=-.43, P=.01), and self-efficacy (beta=.35, P=.03) predicted TTF.
      CONCLUSIONS: Trunk mass appears to be a consistent predictor of performance.
      Kinesiophobia appears to negatively influence TTF for those with a history of
      recurrent low back pain, but does not influence healthy individuals. Self
      efficacy is associated with better performance in individuals with a history of
      recurrent low back pain, whereas a less steep median power frequency slope of the
      trunk and hip extensors is associated with better performance in individuals
      without a history of low back pain.

PMID- 30201606
TI  - Phosphoregulation of the intracellular termini of K+-Cl- cotransporter 2 (KCC2)
      enables flexible control of its activity.
AB  - The pivotal role of K+-Cl- cotransporter 2 (KCC2) in inhibitory neurotransmission
      and severe human diseases fosters interest in understanding posttranslational
      regulatory mechanisms such as (de)phosphorylation. Here, the regulatory role of
      the five bona fide phosphosites Ser31, Thr34, Ser932, Thr999, and Thr1008 was
      investigated by the use of alanine and aspartate mutants. Tl+-based flux analyses
      in HEK-293 cells demonstrated increased transport activity for S932D (mimicking
      phosphorylation) and T1008A (mimicking dephosphorylation), albeit to a different
      extent. Increased activity was due to changes in intrinsic activity, as it was
      not caused by increased cell-surface abundance. Substitutions of Ser31, Thr34, or
      Thr999 had no effect. Additionally, we show that the indirect actions of the
      known KCC2 activators staurosporine and N-ethylmaleimide (NEM) involved multiple
      phosphosites. S31D, T34A, S932A/D, T999A, or T1008A/D abrogated staurosporine
      mediated stimulation, and S31A, T34D, or S932D abolished NEM-mediated
      stimulation. This demonstrates for the first time differential effects of
      staurosporine and NEM on KCC2. In addition, the staurosporine-mediated effects
      involved both KCC2 phosphorylation and dephosphorylation with Ser932 and Thr1008
      being bona fide target sites. In summary, our data reveal a complex
      phosphoregulation of KCC2 that provides the transporter with a toolbox for graded
      activity and integration of different signaling pathways.

PMID- 30201608
TI  - Conjugation inhibitors compete with palmitic acid for binding to the conjugative
      traffic ATPase TrwD, providing a mechanism to inhibit bacterial conjugation.
AB  - Bacterial conjugation is a key mechanism by which bacteria acquire antibiotic
      resistance. Therefore, conjugation inhibitors (COINs) are promising compounds in
      the fight against the spread of antibiotic resistance genes among bacteria.
      Unsaturated fatty acids (uFAs) and alkynoic fatty acid derivatives, such as 2
      hexadecanoic acid (2-HDA), have been reported previously as being effective
      COINs. The traffic ATPase TrwD, a VirB11 homolog in plasmid R388, is the
      molecular target of these compounds, which likely affect binding of TrwD to
      bacterial membranes. In this work, we demonstrate that COINs are abundantly
      incorporated into Escherichia coli membranes, replacing palmitic acid as the
      major component of the membrane. We also show that TrwD binds palmitic acid, thus
      facilitating its interaction with the membrane. Our findings also suggest that
      COINs bind TrwD at a site that is otherwise occupied by palmitic acid.
      Accordingly, molecular docking predictions with palmitic acid indicated that it
      shares the same binding site as uFAs and 2-HDA, although it differs in the
      contacts involved in this interaction. We also identified 2-bromopalmitic acid, a
      palmitate analog that inhibits many membrane-associated enzymes, as a compound
      that effectively reduces TrwD ATPase activity and bacterial conjugation.
      Moreover, we demonstrate that 2-bromopalmitic and palmitic acids both compete for
      the same binding site in TrwD. Altogether, these detailed findings open up a new
      avenue in the search for effective synthetic inhibitors of bacterial conjugation,
      which may be pivotal for combating multidrug-resistant bacteria.

PMID- 30201607
TI  - Protein kinase A phosphorylates the Nem1-Spo7 protein phosphatase complex that
      regulates the phosphorylation state of the phosphatidate phosphatase Pah1 in
      yeast.
AB  - The Nem1-Spo7 protein phosphatase plays a role in lipid synthesis by controlling
      the membrane localization of Pah1, the diacylglycerol-producing phosphatidate
      (PA) phosphatase that is crucial for the synthesis of triacylglycerol in the
      yeast Saccharomyces cerevisiae By dephosphorylating Pah1, Nem1-Spo7 facilitates
      its translocation to the nuclear/endoplasmic reticulum membrane for catalytic
      activity. Like its substrate Pah1, Nem1-Spo7 is phosphorylated in the cell, but
      the specific protein kinases involved remain to be identified. In this study, we
      demonstrate that the Nem1-Spo7 complex is phosphorylated by protein kinase A
      (PKA), which is associated with active cell growth, metabolic activity, and
      membrane phospholipid synthesis. In vitro phosphorylation of purified Nem1-Spo7
      and of their synthetic peptides revealed that both subunits of the phosphatase
      complex are PKA substrates. Using phosphoamino acid and phosphopeptide-mapping
      analyses coupled with site-directed mutagenesis, we identified Ser-140 and Ser
      210 of Nem1 and Ser-28 of Spo7 as PKA-targeted phosphorylation sites.
      Immunodetection of the phosphatase complex from the cell with anti-PKA substrate
      antibody confirmed the in vivo phosphorylations of Nem1 and Spo7 on the serine
      residues. Lipid-labeling analysis of cells bearing phosphorylation-deficient
      alleles of NEM1 and SPO7 indicated that the PKA phosphorylation of the
      phosphatase complex stimulates phospholipid synthesis and attenuates the
      synthesis of triacylglycerol. This work advances the understanding of how PKA
      mediated posttranslational modifications of Nem1 and Spo7 regulate lipid
      synthesis in yeast.

PMID- 30201610
TI  - Better together: patient partnership in medical journals.

PMID- 30201609
TI  - mTORC2 modulates the amplitude and duration of GFAT1 Ser-243 phosphorylation to
      maintain flux through the hexosamine pathway during starvation.
AB  - The mechanistic target of rapamycin (mTOR) controls metabolic pathways in
      response to nutrients. Recently, we have shown that mTOR complex 2 (mTORC2)
      modulates the hexosamine biosynthetic pathway (HBP) by promoting the expression
      of the key enzyme of the HBP, glutamine:fructose-6-phosphate aminotransferase 1
      (GFAT1). Here, we found that GFAT1 Ser-243 phosphorylation is also modulated in
      an mTORC2-dependent manner. In response to glutamine limitation, active mTORC2
      prolongs the duration of Ser-243 phosphorylation, albeit at lower amplitude.
      Blocking glycolysis using 2-deoxyglucose robustly enhances Ser-243
      phosphorylation, correlating with heightened mTORC2 activation, increased AMPK
      activity, and O-GlcNAcylation. However, when 2-deoxyglucose is combined with
      glutamine deprivation, GFAT1 Ser-243 phosphorylation and mTORC2 activation remain
      elevated, whereas AMPK activation and O-GlcNAcylation diminish. Phosphorylation
      at Ser-243 promotes GFAT1 expression and production of GFAT1-generated
      metabolites including ample production of the HBP end-product, UDP-GlcNAc,
      despite nutrient starvation. Hence, we propose that the mTORC2-mediated increase
      in GFAT1 Ser-243 phosphorylation promotes flux through the HBP to maintain
      production of UDP-GlcNAc when nutrients are limiting. Our findings provide
      insights on how the HBP is reprogrammed via mTORC2 in nutrient-addicted cancer
      cells.

PMID- 30201611
TI  - Clinical implications of the Third International Consensus Definitions for Sepsis
      and Septic Shock (Sepsis-3).

PMID- 30201612
TI  - We need smarter trigger tools for diagnosing sepsis in children in Canada.

PMID- 30201613
TI  - Susceptible period for cardiovascular complications in patients recovering from
      sepsis.
AB  - BACKGROUND: Patients are at increased risk of cardiovascular complications while
      recovering from sepsis. We aimed to study the temporal change and susceptible
      periods for cardiovascular complications in patients recovering from sepsis by
      using a national database. METHODS: In this retrospective population-based cohort
      study, patients with sepsis were identified from the National Health Insurance
      Research Database in Taiwan. We estimated the risk of myocardial infarction (MI)
      and stroke following sepsis by comparing a sepsis cohort to a matched population
      and hospital control cohort. The primary outcome was first occurrence of MI or
      stroke requiring admission to hospital during the 180-day period following
      discharge from hospital after sepsis. To delineate the risk profile over time, we
      plotted the weekly risk of MI and stroke against time using the Cox proportional
      hazards model. We determined the susceptible period by fitting the 2 phases of
      time-dependent risk curves with free-knot splines, which highlights the turning
      point of the risk of MI and stroke after discharge from the hospital. RESULTS: We
      included 42 316 patients with sepsis; stroke developed in 831 of these patients
      and MI developed in 184 within 180 days of discharge from hospital. Compared with
      population controls, patients recovering from sepsis had the highest risk for MI
      or stroke in the first week after discharge (hazard ratio [HR] 4.78, 95%
      confidence interval [CI] 3.19 to 7.17; risk difference 0.0028, 95% CI 0.0021 to
      0.0034), with the risk decreasing rapidly until the 28th day (HR 2.38, 95% CI
      1.94 to 2.92; risk difference 0.0045, 95% CI 0.0035 to 0.0056) when the risk
      stabilized. In a repeated analysis comparing the sepsis cohort with the nonsepsis
      hospital control cohort, we found an attenuated but still marked elevated risk
      before day 36 after discharge (HR 1.32, 95% CI 1.15 to 1.52; risk difference
      0.0026, 95% CI 0.0013 to 0.0039). The risk of MI or stroke was found to interact
      with age, with younger patients being associated with a higher risk than older
      patients (interaction p = 0.0004). INTERPRETATION: Compared with the general
      population with similar characteristics, patients recovering from sepsis had a
      markedly elevated risk of MI or stroke in the first 4 weeks after discharge from
      hospital. More close monitoring and pharmacologic prevention may be required for
      these patients at the specified time.

PMID- 30201614
TI  - Renal complications and subsequent mortality in acute critically ill patients
      without pre-existing renal disease.
AB  - BACKGROUND: Most studies of long-term renal outcomes after acute critical illness
      have enrolled patients with pre-existing renal dysfunction. We assessed renal
      outcomes in patients who did not have pre-existing renal disease and who were
      admitted to hospital for acute critical illness. METHODS: We identified adults
      who did not have pre-existing renal disease and who were admitted to hospital for
      acute critical illness between 2000 and 2011, from the Taiwan National Health
      Insurance Research Database. Each patient was matched 1:2 with controls without
      acute critical illness, according to age, sex and index date. A subset was
      further matched 1:1 with controls using propensity scores. Outcomes included
      acute kidney injury, chronic kidney disease and end-stage renal disease. RESULTS:
      We evaluated 33 613 patients with acute critical illness matched to 63 148
      controls, of whom 14 218 were propensity matched to 14 218 controls. Patients
      with acute critical illness had incidence rates per 10 000 person-years of 9.45
      for acute kidney injury, 78.3 for chronic kidney disease and 21.0 for end-stage
      renal disease. In the propensity-matched cohort, patients with acute critical
      illness had significantly higher risks of acute kidney injury (adjusted hazard
      ratio [aHR] 2.92, 95% confidence interval [CI] 1.78-4.77), chronic kidney disease
      (aHR 1.81, 95% CI 1.57-2.08), and end-stage renal disease (aHR 3.60, 95% CI 2.50
      5.18). Acute critical illness conferred higher mortality risk among patients who
      subsequently developed end-stage renal disease (aHR 3.37, 95% CI 2.07-5.49) or
      chronic kidney disease (aHR 2.16, 95% CI 1.67-2.80). INTERPRETATION: Patients
      with acute critical illness and without pre-existing renal disease have a higher
      risk of adverse renal outcomes and subsequent mortality. A resolved episode of
      critical illness has implications for future renal function surveillance, even in
      patients without pre-existing renal disease.

PMID- 30201615
TI  - A 38-year-old man with fever and a history of malaria.

PMID- 30201616
TI  - Sepsis-associated encephalopathy.

PMID- 30201617
TI  - Invasive pneumococcal infection in a man with hyposplenism.

PMID- 30201618
TI  - Early referral for hoarseness.

PMID- 30201619
TI  - Hoarseness of unclear origin may be a sign of cerebrovascular disease and herald
      impending recurrent brainstem stroke.

PMID- 30201620
TI  - Canadian health care lacks culture of innovation.

PMID- 30201621
TI  - Medical technology often a burden if designed without physician input.

PMID- 30201622
TI  - Emotions flare in tense but civil CMA annual meeting.

PMID- 30201623
TI  - Early Language Exposure and Middle School Language and IQ: Implications for
      Primary Prevention.

PMID- 30201624
TI  - Language Experience in the Second Year of Life and Language Outcomes in Late
      Childhood.
AB  - OBJECTIVES: Quantity of talk and interaction in the home during early childhood
      is correlated with socioeconomic status (SES) and can be used to predict early
      language and cognitive outcomes. We tested the effectiveness of automated early
      language environment estimates for children 2 to 36 months old to predict
      cognitive and language skills 10 years later and examined effects for specific
      developmental age periods. METHODS: Daylong audio recordings for 146 infants and
      toddlers were completed monthly for 6 months, and the total number of daily adult
      words and adult-child conversational turnswere automatically estimated with
      Language Environment Analysis software. Follow-up evaluations at 9 to 14 years of
      age included language and cognitive testing. Language exposure for 3 age groups
      was assessed: 2 to 17 months, 18 to 24 months, and >=25 months. Pearson
      correlations and multiple linear regression analyses were conducted. RESULTS:
      Conversational turn counts at 18 to 24 months of age accounted for 14% to 27% of
      the variance in IQ, verbal comprehension, and receptive and/or expressive
      vocabulary scores 10 years later after controlling for SES. Adult word counts
      between 18 and 24 months were correlated with language outcomes but were
      considerably weakened after controlling for SES. CONCLUSIONS: These data support
      the hypothesis that early talk and interaction, particularly during the
      relatively narrow developmental window of 18 to 24 months of age, can be used to
      predict school-age language and cognitive outcomes. With these findings, we
      underscore the need for effective early intervention programs that support
      parents in creating an optimal early language learning environment in the home.

PMID- 30201625
TI  - The Role of Integrated Care in a Medical Home for Patients With a Fetal Alcohol
      Spectrum Disorder.
AB  - Fetal alcohol spectrum disorder (FASD) is an umbrella term used to describe
      preventable birth defects and intellectual and/or developmental disabilities
      resulting from prenatal alcohol exposure. The American Academy of Pediatrics has
      a previous clinical report in which diagnostic criteria for a child with an FASD
      are discussed and tools to assist pediatricians with its management can be found.
      This clinical report is intended to foster pediatrician awareness of approaches
      for screening for prenatal alcohol exposure in clinical practice, to guide
      management of a child with an FASD after the diagnosis is made, and to summarize
      available resources for FASD management.

PMID- 30201626
TI  - Adolescent Use of Different E-cigarette Products.
AB  - : : media-1vid110.1542/5804914521001PEDS-VA_2018-0260Video Abstract BACKGROUND:
      Little is known about the characteristics of electronic cigarettes (e-cigarettes)
      used by adolescents. Understanding the product landscape of adolescent e
      cigarette use may inform counseling and policy strategies. METHODS: Results are
      from 13 651 adolescents in wave 1 and 12 172 adolescents in wave 2 of the
      Population Assessment of Tobacco and Health Study, a nationally representative
      longitudinal study. Past 30-day regular e-cigarettes users were asked about the
      characteristics of the e-cigarette they used most of the time. RESULTS: In waves
      1 and 2, 2.1% and 2.8% of adolescents were regular users in the past 30 days,
      respectively. These adolescents more often used rechargeable rather than
      disposable devices (wave 1: 76.0%; wave 2: 82.9%) and refillable rather than
      nonrefillable devices (wave 1: 66.6%; wave 2: 84.4%) and tended not to use
      cartridge systems (wave 1: 33.7%; wave 2: 30.5%). Most adolescent past 30-day
      users (wave 1: 87.5%; wave 2: 89.4%) reported using flavored e-cigarettes. An
      increased frequency of use was associated with the use of rechargeable (wave 1
      adjusted odds ratio [aOR]: 2.7; wave 2 aOR: 2.7) and refillable e-cigarettes
      (wave 1 aOR: 2.0; wave 2 aOR: 2.7; P < .05). Most users in wave 1 did not
      continue regular use in wave 2 (70.2%). Among those who continued to use and had
      reported using closed systems (nonrechargeable and/or nonrefillable) in wave 1,
      most had progressed to open systems (rechargeable and refillable) in wave 2.
      CONCLUSIONS: Most adolescents use open-system e-cigarettes, and frequent users
      are even more likely to use open-system e-cigarettes. The majority of regular
      users use rechargeable devices that are refillable. A change in product
      preferences across waves suggests a starter product phenomenon, with a graduation
      to products that have weaker quality controls and may increase health risks.

PMID- 30201627
TI  - Microwave weapon caused syndrome in diplomats in Cuba, US medical team believes.

PMID- 30201628
TI  - Alder Hey's "cognitive hospital" aims to turn NHS use of AI on its head.

PMID- 30201629
TI  - CQC: Trusts must do more to protect mental health patients from sexual abuse.

PMID- 30201631
TI  - Signaling through non-membrane nuclear phosphoinositide binding proteins in human
      health and disease.
AB  - Phosphoinositide membrane signaling is critical for normal physiology, playing
      well-known roles in diverse human pathologies. The basic mechanisms governing
      phosphoinositide signaling within the nucleus, however, have remained deeply
      enigmatic owing to their presence outside the nuclear membranes. Over 40% of
      nuclear phosphoinositides can exist in this non-membrane state, held soluble in
      the nucleoplasm by nuclear proteins that remain largely unidentified. Recently,
      two nuclear proteins responsible for solubilizing phosphoinositides were
      identified - steroidogenic factor-1 (SF-1, NR5A1) and liver receptor homolog-1
      (LRH-1, NR5A2) - along with two enzymes that directly remodel these
      phosphoinositide/protein complexes - phosphatase and tensin homolog (PTEN, MMAC)
      and inositol polyphosphate multikinase (IPMK, ipk2). These new footholds now
      permit the assignment of physiological functions for nuclear phosphoinositides in
      human diseases, such as endometriosis, non-alcoholic fatty liver disease /
      steatohepatitis, glioblastoma and hepatocellular carcinoma. The unique nature of
      nuclear phosphoinositide signaling affords extraordinary clinical opportunities
      for new biomarkers, diagnostics and therapeutics. Thus, phosphoinositide biology
      within the nucleus may represent the next generation of low-hanging fruit for new
      drugs, not unlike what has occurred for membrane PI3-kinase drug development.
      This review connects recent basic science discoveries in nuclear phosphoinositide
      signaling to clinical pathologies, with the hope of inspiring development of new
      therapies.

PMID- 30201630
TI  - Novel fatty acyl apoE mimetic peptides have increased potency to reduce plasma
      cholesterol in mice and macaques.
AB  - Ac-hE18A-NH2 is a dual-domain apoE mimetic peptide that possesses the putative
      receptor binding domain from apoE (LRKLRKRLLR, denoted hE; residues 141-150)
      covalently attached to lipid-associating peptide 18A. Like apoE, Ac-hE18A-NH2
      reduces plasma cholesterol in animal models and exhibits anti-inflammatory
      properties independent of its cholesterol-reducing effect. Ac-hE18A-NH2 has
      already undergone phase I clinical trials as a lipid-lowering agent. To explore
      the therapeutic potential more, we designed and synthesized new analogues by
      linking alpha-aminohexanoic acid, octanoic acid, or myristic acid to LRRLRRRLLR
      18A-NH2 ([R]hE18A-NH2) and examined the cholesterol-lowering potency in animals.
      The modified peptides effectively reduced plasma cholesterol in apoE-null mice
      fed standard chow or a Western diet; the myristyl analogue was the most
      effective. A single administration of the myristyl analogue reduced plasma total
      and LDL cholesterol in a dose-dependent manner in hypercholesterolemic cynomolgus
      macaques for up to 1 week despite the continuation of a cholesterol-supplemented
      diet. The myristyl peptide (7.4 mg/kg) reduced total and LDL cholesterol at 24 h
      by 64% and 74%, respectively; plasma HDL levels were modestly reduced and
      returned to baseline by day 7. These new analogues should exhibit enhanced
      potency at lower doses than Ac-hE18A-NH2, which may make them attractive
      therapeutic candidates for clinical trials.

PMID- 30201633
TI  - The Long Loneliness of Primary Care.

PMID- 30201632
TI  - WITHDRAWN: The Fundamental And Pathological Importance Of Oxysterol Binding
      Protein And Its Related Proteins.
AB  - This article has been withdrawn by the authors as part of this review overlapped
      with the contents of Pietrangelo A and Ridgway ND. 2018. Cellular and Molecular
      Life Sciences. 75; 3079-98.

PMID- 30201634
TI  - Clinical Prediction Rules: Challenges, Barriers, and Promise.

PMID- 30201635
TI  - Social Isolation and Patient Experience in Older Adults.
AB  - PURPOSE: Social isolation has been identified as a major health problem,
      particularly in the elderly. In the present study, we examine the association
      between social isolation and patient experience in elderly primary care patients.
      METHODS: This cross-sectional study was conducted in a primary care practice
      based research network (28 clinics) in Japan. We assessed social isolation using
      an abbreviated Lubben Social Network Scale and patient experience of primary care
      using a Japanese version of the Primary Care Assessment Tool (JPCAT), which
      comprises 6 domains: first contact, longitudinality, coordination,
      comprehensiveness (services available), comprehensiveness (services provided),
      and community orientation. We used a linear mixed effects model to adjust
      clustering within clinics and individual covariates. RESULTS: Data were analyzed
      for 465 elderly primary care patients aged >=65 years. After adjustment for
      possible confounders and clustering within clinics, social isolation was
      negatively associated with the JPCAT total score, (mean difference = -3.67; 95%
      CI, -7.00 to -0.38). Among the JPCAT domain scores, social isolation was
      significantly associated with longitudinality, comprehensiveness (service
      provided), and community orientation scores. CONCLUSIONS: Social isolation was
      associated with negative patient experience in elderly primary care patients.
      Raising awareness regarding patient social networks among primary care providers
      and targeted interventions for socially isolated elderly patients aimed at
      improving the experience of primary care, especially regarding longitudinality,
      comprehensiveness, and community orientation, may be warranted.

PMID- 30201637
TI  - Excess Free Fructose Beverages and Allergy in Children and Adolescents: Results
      From NHANES 2005-2006.
AB  - PURPOSE: Our purpose was to investigate the relationship between intake of excess
      free fructose beverages and allergy among children and adolescents. METHODS: We
      analyzed data of 860 children (aged 6 to 12 years) and 1,142 adolescents (aged 13
      to 19 years) from the National Health and Nutrition Examination Survey 2005-2006.
      Logistic regression analyses were performed to determine the associations between
      consumption of excess free fructose beverages and allergic symptoms or allergic
      sensitization. RESULTS: The pattern of findings was not entirely consistent, but
      some analyses supported the hypothesis of an association between intake of excess
      free fructose beverages and allergy. After controlling for the potential
      confounders, children who consumed nondiet fruit drinks at least 5 times per week
      had a nearly 2.5-fold greater odds of allergic sensitization than did those who
      consumed such drinks only 1 to 3 times per month (OR = 2.446; 95% CI, 1.583
      3.780). Adolescents who consumed excess free fructose beverages at least 5 times
      per week or 1 to 4 times per week had about fivefold greater odds of presence of
      allergic symptoms than did those who seldom consumed these beverages (OR = 5.164;
      95% CI, 1.866-14.297 and OR = 4.112; 95% CI, 1.857-9.107, respectively).
      Adolescents who consumed apple juice at least 5 times per week had a twofold
      greater odds of presence of allergic sensitization than did the seldom consumers
      (OR = 2.215; 95% CI, 1.178-4.164). CONCLUSIONS: These findings provide some
      support for the hypothesis of a link between intake of excess free fructose
      beverages and allergic symptoms or allergic sensitization in children and
      adolescents.

PMID- 30201636
TI  - Adoption of Social Determinants of Health EHR Tools by Community Health Centers.
AB  - PURPOSE: This pilot study assessed the feasibility of implementing electronic
      health record (EHR) tools for collecting, reviewing, and acting on patient
      reported social determinants of health (SDH) data in community health centers
      (CHCs). We believe it is the first such US study. METHODS: We implemented a suite
      of SDH data tools in 3 Pacific Northwest CHCs in June 2016, and used mixed
      methods to assess their adoption through July 2017. We modified the tools at
      clinic request; for example, we added questions that ask if the patient wanted
      assistance with SDH needs. RESULTS: Social determinants of health data were
      collected on 1,130 patients during the study period; 97% to 99% of screened
      patients (n = 1,098) had >=1 SDH need documented in the EHR, of whom 211 (19%)
      had an EHR-documented SDH referral. Only 15% to 21% of patients with a documented
      SDH need indicated wanting help. Examples of lessons learned on adoption of EHR
      SDH tools indicate that clinics should: consider how to best integrate tools into
      existing workflow processes; ensure that staff tasked with SDH efforts receive
      adequate tool training and access; and consider that timing of data entry impacts
      how and when SDH data can be used. CONCLUSIONS: Our results indicate that
      adoption of systematic EHR-based SDH documentation may be feasible, but
      substantial barriers to adoption exist. Lessons from this study may inform
      primary care providers seeking to implement SDH-related efforts, and related
      health policies. Far more research is needed to address implementation barriers
      related to SDH documentation in EHRs.

PMID- 30201638
TI  - Emergency Department Use and Enrollment in a Medical Home Providing After-Hours
      Care.
AB  - PURPOSE: Compared with other high-income countries, Canada and the United States
      have among the highest rates of emergency department use and the lowest rates of
      primary care physicians reporting arrangements for after-hours care. We assessed
      whether enrollment in a medical home mandated to provide after-hours care in
      Ontario, Canada, was associated with reduced emergency department use. METHODS:
      We conducted a retrospective cohort study using linked administrative data. We
      included all adult Ontarians enrolled in a medical home between April 1, 2005,
      and March 31, 2012, who had a minimum of 3 years of outcome data before and after
      enrollment (N = 2,945,087). We performed a linear segmented analysis with patient
      level data to understand the association between initial enrollment in a medical
      home and emergency department visits, the proportion of all primary care visits
      occurring on the weekend, and the primary care visit rate. Age, income quintile,
      comorbidity, and morbidity were included in the modeling as time-varying
      covariates and sex as a stable variable. RESULTS: The emergency department visit
      rate increased by 0.8% (95% CI, 0.7% to 0.9%) per year before medical home
      enrollment and by 1.5% (95% CI, 1.4% to 1.5%) per year after the transition.
      Enrollment in a medical home was associated with an increase in the proportion of
      visits that occurred on weekends, but a decrease in the overall primary care
      visit rate. CONCLUSIONS: Enrollment of adult Ontarians in a primary care medical
      home offering after-hours care was not associated with a reduction in emergency
      department use. It will therefore be important to prospectively evaluate policy
      reforms aimed at improving access to primary care outside of conventional hours.

PMID- 30201639
TI  - Predicting an Unfavorable Course of Dizziness in Older Patients.
AB  - PURPOSE: Because dizziness in older people is often chronic and can substantially
      affect daily functioning, it is important to identify those at risk for an
      unfavorable course of dizziness to optimize their care. We aimed to develop and
      externally validate a prediction model for an unfavorable course of dizziness in
      older patients in primary care, and to construct an easy-to-use risk prediction
      tool. METHODS: We used data from 2 prospective cohorts: a development cohort with
      203 patients aged 65 years or older who consulted their primary care physician
      for dizziness and had substantial dizziness-related impairment (Dizziness
      Handicap Inventory [DHI] >=30), and a validation cohort with 415 patients aged 65
      years or older who consulted their primary care physician for dizziness of any
      severity. An unfavorable course was defined as presence of substantial dizziness
      related impairment (DHI >=30) after 6 months. RESULTS: Prevalence of an
      unfavorable course of dizziness was 73.9% in the development cohort and 43.6% in
      the validation cohort. Predictors in the final model were the score on the
      screening version of the DHI, age, history of arrhythmia, and looking up as a
      provoking factor. The model showed good calibration and fair discrimination (area
      under the curve = 0.77). On external validation, discriminative ability remained
      stable (area under the curve = 0.78). The constructed risk score was strongly
      correlated with the prediction model. Performance measures for risk score cut-off
      values are presented to determine the optimal cut-off point for clinical
      practice. CONCLUSIONS: We developed an easy-to-use risk score for dizziness
      related impairment in primary care. The risk score, consisting of only 4
      predictors, will help primary care physicians identify patients at high risk for
      an unfavorable course of dizziness.

PMID- 30201640
TI  - Top 20 POEMs of the Past 20 Years: A Survey of Practice-Changing Research for
      Family Physicians.
AB  - POEMs (patient-oriented evidence that matters) are studies that address a
      relevant clinical question, demonstrate improved patient-oriented outcomes, and
      have the potential to change practice. For 20 years the authors of this article
      have reviewed more than 100 English language clinical journals monthly to
      identify POEMs in the medical literature relevant to primary care practice. This
      article identifies the POEMs in each of the last 20 years that were highest
      ranked for having recommended a major and persistent change in practice that
      year. They include POEMs that recommend a novel, effective intervention, a second
      group that recommends abandoning an ineffective practice, and a third group that
      recommends abandoning a potentially harmful practice. The top POEMs of the past
      20 years illustrate the breadth of practice change in primary care and the need
      for family physicians to have a systematic approach to keeping up with the
      medical literature, such as that in POEMs, especially because many of these
      important articles did not appear in the primary care literature.

PMID- 30201642
TI  - Buprenorphine Provision by Early Career Family Physicians.
AB  - Buprenorphine can be used in primary care to treat opioid use disorder, but many
      family physicians feel unprepared to care for patients with opioid addiction. We
      sought to describe preparedness to provide and current provision of buprenorphine
      treatment by early career family physicians using data from the 2016 National
      Family Medicine Graduate Survey. Of 1,979 respondents, 10.0% reported
      preparedness to provide buprenorphine treatment, and 7.0% reported current
      buprenorphine provision. Residency preparation to provide buprenorphine treatment
      was most highly associated with current provision (odds ratio = 13.50; 95% CI,
      7.59-24.03). Efforts to increase buprenorphine training may alleviate the
      workforce shortage to treat opioid use disorder.

PMID- 30201641
TI  - Opioid-Prescribing Continuity and Risky Opioid Prescriptions.
AB  - We aimed to better understand the association between opioid-prescribing
      continuity, risky prescribing patterns, and overdose risk. For this retrospective
      cohort study, we included patients with long-term opioid use, pulling data from
      Oregon's Prescription Drug Monitoring Program (PDMP), vital records, and hospital
      discharge registry. A continuity of care index (COCI) score was calculated for
      each patient, and we defined metrics to describe risky prescribing and overdose.
      As prescribing continuity increased, likelihood of filling risky opioid
      prescriptions and overdose hospitalization decreased. Prescribing continuity is
      an important factor associated with opioid harms and can be calculated using
      administrative pharmacy data.

PMID- 30201644
TI  - Professional Loneliness and the Loss of the Doctors' Dining Room.
AB  - Historically, family physicians moved among all the venues of medical care-
      office, hospital, community-and were a part of a connected professional
      community. That connected community was sustained in great part through informal
      gatherings of clinicians in hospitals, clinics, and professional organizations.
      The current fragmentation of medicine into narrowly defined, boundaried
      workspaces and job descriptions, as well as the increasing size of practices has
      negatively affected the professional culture in which physicians work. These
      structural changes have led to an increasing sense of professional loneliness
      that not only threatens the quality of clinical care by replacing personal
      discussions about patients but also poses risks to physician personal and
      professional wellbeing.

PMID- 30201645
TI  - Scaling Integrated Behavioral Health Rapidly.

PMID- 30201646
TI  - Circling Back to a Better Sexual History.

PMID- 30201647
TI  - Mentored Training Positions for Early-Career General Practitioners.

PMID- 30201648
TI  - Using the Humanism Pocket Tool for Patients With Challenging Behaviors.

PMID- 30201643
TI  - Employment Interventions in Health Settings: A Systematic Review and Synthesis.
AB  - PURPOSE: Employment is a key social determinant of health. People who are
      unemployed typically have worse health than those employed. Illness and
      disability can result in unemployment and be a barrier to regaining employment.
      We combined a systematic review and knowledge synthesis to identify both studies
      of employment interventions in health care settings and common characteristics of
      successful interventions. METHODS: We searched the peer-reviewed literature (1995
      2017), and titles and abstracts were screened for inclusion and exclusion
      criteria by 2 independent reviewers. We extracted data on the study setting,
      participants, intervention, methods, and findings. We also conducted a narrative
      synthesis and iteratively developed a conceptual model to inform future primary
      care interventions. RESULTS: Of 6,729 unique citations, 88 articles met our
      criteria. Most articles (89%) focused on people with mental illness. The majority
      of articles (74%) tested interventions that succeeded in helping participants
      gain employment. We identified 5 key features of successful interventions: (1) a
      multidisciplinary team that communicates regularly and collaborates, (2) a
      comprehensive package of services, (3) one-on-one and tailored components, (4) a
      holistic view of health and social needs, and (5) prospective engagement with
      employers. CONCLUSIONS: Our findings can inform new interventions that focus on
      employment as a social determinant of health. Although hiring a dedicated
      employment specialist may not be feasible for most primary care organizations,
      pathways using existing resources with links to external agencies can be created.
      As precarious work becomes more common, helping patients engage in safe and
      productive employment could improve health, access to health care, and well
      being.

PMID- 30201649
TI  - "THE GME INITIATIVE" AND GME IN STATES.

PMID- 30201650
TI  - OPIOID PRESCRIBING: A GENERATIONAL PERSPECTIVE.

PMID- 30201651
TI  - 2018 PBRN CONFERENCE HIGHLIGHTS: ADDRESSING HEALTH DISPARITIES IN PBRN RESEARCH.

PMID- 30201652
TI  - AAFP OFFERS RESOURCES AS 'JUULING' INCREASES AMONG YOUTH.

PMID- 30201654
TI  - RESIDENCY FACULTY FUNDAMENTALS CERTIFICATE PROGRAM WRAPS UP SUCCESSFUL FIRST
      YEAR.

PMID- 30201653
TI  - NEW CENTER FOR PROFESSIONALISM AND VALUE IN HEALTH CARE OPEN IN WASHINGTON, DC.

PMID- 30201655
TI  - Are New Residency Graduates Prepared to Treat Opioid Use Disorder?

PMID- 30201656
TI  - Physiology, activity and costs of parental care in birds.
AB  - Parental care is assumed to be costly in that it requires sustained, high
      intensity activity sufficient to cause costs of reproduction (decreased survival
      and future fecundity of parents). Costs of reproduction are, in turn, thought to
      have a physiological basis where intense activity causes a decrease in parental
      condition. However, attempts to identify the physiological basis of costs of
      reproduction have produced mixed results. Here, I argue that in birds, the
      central idea that parental care represents sustained, high-intensity work might
      be incorrect. Specifically: (a) the duration of intense activity associated with
      chick-rearing might be quite limited; (b) flight, the most obvious sustained,
      high-intensity activity, might only represent a small component of an
      individual's overall activity budget; (c) some (high-quality) individuals might
      be able to tolerate costs of intense activity, either owing to their
      physiological state or because they have access to more resources, without
      perturbation of physiological homeostasis; and (d) individuals might utilise
      other mechanisms to modulate costs of activity, for example, mass loss, again
      avoiding more substantial physiological costs. Furthermore, I highlight the
      important fact that life-history theory predicts that reproductive trade-offs
      should only be expected under food stress. Most birds breed in spring and early
      summer precisely because of seasonal increases in food abundance, and so it is
      unclear how often parents are food stressed. Consequently, I argue that there are
      many reasons why costs of reproduction, and any physiological signature of these
      costs, might be quite rare, both temporally (in different years) and among
      individuals.

PMID- 30201657
TI  - Correction: Reducing gravity takes the bounce out of running
      (doi:10.1242/jeb.162024).

PMID- 30201658
TI  - Use of clinical decision support to identify i.v.-to-oral conversion
      opportunities and cost savings.
AB  - PURPOSE: The use of a clinical decision support (CDS) tool to determine patients'
      eligibility for oral medication therapy and the opportunity cost of i.v.-to-oral
      conversion practices in a large health system was evaluated. METHODS: This
      multicenter, retrospective, process improvement study comprised CDS data
      generated by 149 hospitals from May 1 through October 31, 2015. Data related to
      i.v.-to-oral conversions were identified and compiled for evaluation. For each
      patient with an opportunity for i.v.-to-oral therapy conversion, corresponding
      barcode-assisted medication administration data were evaluated to determine the
      number of doses that were administered within prespecified time periods. RESULTS:
      A total of 121,685 i.v.-to-oral conversion opportunities, corresponding to 71,342
      unique patients and encompassing 31 different medications, were evaluated. The
      top 13 medications representing 94% of the total number of alerts and over 1.4
      million doses were included for analysis. Current i.v.-to-oral conversion
      practices saved the hospitals 9% on medication costs. Upon further evaluation,
      additional cost savings of 29-78% for those 13 medications could be achieved with
      more timely conversion from i.v. to oral therapy. CONCLUSION: Hospital
      pharmacists' i.v.-to-oral conversion practices with the CDS tool resulted in
      medication cost savings of 9%, or $1.48 million, for 13 medications evaluated
      over a 6-month period.

PMID- 30201659
TI  - Anaesthetist suspended after GMC appeal to High Court.

PMID- 30201660
TI  - Health Care Integration and Coordination with Emphasis on Mental Health, but Not
      for Medical Marijuana.
AB  - Care coordination and behavioral health care integration are the subject of 4 of
      this month's articles. Patients with significant illness report that care
      coordination provides great challenges to them, and they expect family physicians
      to assist with the referrals and communication between the doctors. Patients'
      primary care providers were usually not the prescribers of patients' medical
      marijuana and were often unaware of its use, indicating lack of health care
      integration and coordination. Two articles provide insight into medication
      adherence. Also, how are family physicians addressing patient engagement at the
      practice level? Clinical topics in this issue include the following: specific
      exercises were not the answer to restless legs; epidural anesthesia may be
      associated with fewer, not more, vaginal lacerations; and fecal incontinence is
      less discussed but not necessarily less problematic than urinary incontinence. On
      the popular culture front, opioid mentions in top 100 songs are increasing.
      Lastly, what does it mean for the field of family medicine that some of us choose
      to become hospitalists?

PMID- 30201661
TI  - Beware of Predatory Journals: A Caution from Editors of Three Family Medicine
      Journals.

PMID- 30201662
TI  - Family Medicine Hospitalists Three Years Out of Residency: Career Flexibility or
      a Threat to Office-Based Family Medicine?

PMID- 30201663
TI  - Characteristics of Young Family Physician Hospitalists.
AB  - Based on a 2016 survey of family physicians who were then three years out of
      residency training, we found that almost 9 percent self-identified as
      hospitalists. These family physician hospitalists were significantly more likely
      than their non-hospitalist peers to be male, work longer hours, be better paid,
      and be more satisfied with their work. These attributes may attract more family
      physicians to hospital medicine, with negative implications for the supply of
      primary care physicians. (J Am Board Fam Med 2018;31:680-681.).

PMID- 30201664
TI  - "It's Really Overwhelming": Patient Perspectives on Care Coordination.
AB  - PURPOSE: Failures of care coordination among health care providers are known to
      lead to poorer health outcomes for patients with complex medical needs. However,
      there has been limited research into the perspectives of patients who receive
      care from a variety of health care providers. This qualitative study sought to
      characterize the factors leading to emergency department (ED) patient
      satisfaction and dissatisfaction with their care coordination. METHODS:
      Semistructured telephone interviews were conducted with 25 adult patients
      following ED visits about their experiences with their care coordination. All
      patients interviewed had 2 or more ED visits and hospitalizations in the past
      year and/or health providers in more than one health system. Interview
      transcripts were coded and analyzed following a modified grounded theory
      approach. RESULTS: Four broad categories of themes emerged from the patient
      interviews covering the following: (1) perceptions of care coordination between
      their providers, (2) the role of electronic health records, (3) challenges with
      information exchange between health systems, and (4) sources of support for care
      coordination activities, emphasizing the important role of the primary care
      provider. CONCLUSIONS: Patients with multiple health care providers identified
      significant barriers to communication among providers and inadequate support with
      care coordination activities. Expansion of team-based models of primary care and
      prioritizing interoperable technology for sharing patient health information
      between providers will be critical to improving the patient experience and the
      safety of transitions of care.

PMID- 30201665
TI  - Approaches to Behavioral Health Integration at High Performing Primary Care
      Practices.
AB  - INTRODUCTION: Behavioral health (BH) integration has been proposed as an
      important strategy to help primary care practices meet the needs of their patient
      population, but there is little research on the ways in which practices are
      integrating BH services. This article describes the goals for BH integration at
      30 high-performing primary care practices and strategies to operationalize these
      goals. METHODS: We conducted a qualitative analysis of BH integration at 30 US
      primary care practices that had been selected for the Learning from Effective
      Ambulatory Practices (LEAP) project following an interview-based assessment and
      rating process. Data collection included formal and informal interviews with
      practice leaders and staff, as well as observations of clinical encounters. We
      used a template analysis approach to thematically analyze data. RESULTS: Most
      LEAP practices looked to BH integration to help them provide timely BH care for
      all patients, share the work of providing BH-related care, meet the full spectrum
      of patient needs, and improve the capacity and functioning of care teams.
      Practices operationalized these goals in various ways, including universal BH
      screening and involving BH specialists in chronic illness care. As they worked
      toward their BH integration goals, LEAP practices faced common challenges related
      to staffing, health information technology, funding, and community resources.
      DISCUSSION: High-performing primary care practices share common goals for BH
      integration, as well as common challenges operationalizing these goals. As US
      residents increasingly receive BH services in primary care, it is critical to
      remove barriers to BH integration and support primary care practices in meeting a
      full spectrum of patient needs.

PMID- 30201666
TI  - Large-Scale Implementation of Collaborative Care Management for Depression and
      Diabetes and/or Cardiovascular Disease.
AB  - BACKGROUND: Collaborative care models have been shown to improve mental and
      physical health, but their effectiveness varies. Implementation science
      frameworks identify measures at the structural (eg, sociocultural context, public
      policies), organizational, provider, innovation, and patient levels that may
      facilitate or impede collaborative care effectiveness. OBJECTIVE: To describe
      commonalities and variation in multilevel measures associated with the
      implementation of Care of Mental, Physical, and Substance-Use Syndromes
      (COMPASS), a large-scale collaborative care intervention for depression,
      diabetes, and cardiovascular disease. DESIGN: Qualitative study using
      semistructured descriptive data obtained from annual site visit reports and
      supplemental site surveys. PARTICIPANTS: COMPASS care teams from 8 health care
      systems serving 3854 patients with active depression and poorly controlled
      diabetes and/or cardiovascular disease. INTERVENTION: COMPASS included weekly
      case reviews with a consulting physician and psychiatrist, a patient-tracking
      registry, and monitoring of hospital and emergency department use. MAIN MEASURES:
      Site visit reports were analyzed with Atlas.ti software to qualitatively describe
      implementation measures and their variation across sites. KEY RESULTS: Nine
      measures were identified that impacted implementation efforts across health
      systems: (1) challenges in health systems' organizational environments, (2) prior
      care coordination experience, (3) physician engagement, (4) care team trust and
      cohesion, (5) care manager training and experience, (6) patient enrollment
      length, attainment of clinical targets, and frequency/content of care manager
      contacts, (7) patient-tracking registries, (8) quality improvement and outcomes
      monitoring reports, and (9) patients' social needs. CONCLUSIONS: Understanding
      multilevel measures impacting COMPASS implementation could increase the success
      of future collaborative care implementation efforts.

PMID- 30201667
TI  - Evaluation of an Electronic Health Record (EHR) Tool for Integrated Behavioral
      Health in Primary Care.
AB  - BACKGROUND: Integrating behavioral health into primary care can improve care
      quality; however, most electronic health records are not designed to meet the
      needs of integrated teams. We worked with practices and behavioral health (BH)
      clinicians to design a suite of electronic health record tools to address these
      needs ("BH e-Suite"). The purpose of this article is to examine whether
      implementation of the BH e-Suite changes process of care, intermediate clinical
      outcomes, and patient experiences, and whether its use is acceptable to practice
      members and BH clinicians. METHODS: We conducted a convergent mixed-methods proof
      of-concept study, implementing the BH e-Suite across 6 Oregon federally qualified
      community health centers ("intervention clinics"). We matched intervention
      clinics to 6 control clinics, based on location and patient panel
      characteristics, to assess whether process of care (Patient Health Questionnaire
      9 [PHQ-9] and Generalized Anxiety Disorder-7 screening) and intermediate outcomes
      (PHQ-9, Generalized Anxiety Disorder-7 scores) changed postimplementation.
      Prepost patient surveys were used to assess changes in patient experience. To
      elucidate factors influencing implementation, we merged quantitative findings
      with structured observations, surveys, and interviews with practice members.
      RESULTS: Implementation improved process of care (PHQ-9 screening). During the
      course of the study, change in intermediate outcomes was not observed. Degree of
      BH e-Suite implementation varied: 2 clinics fully implemented, 2 partially
      implemented, and 2 practices did not implement at all. Initial practice
      conditions (eg, low resistance to change, higher capacity), process
      characteristics (eg, thoughtful planning), and individual characteristics (eg,
      high self-efficacy) were related to degree of implementation. CONCLUSIONS: Health
      information technology tools designed for behavioral health integration must fit
      the needs of clinics for the successful uptake and improvement in patient
      experiences. Research is needed to further assess the effectiveness of this tool
      in improving patient outcomes and to optimize broader dissemination of this tool
      among primary care clinics integrating behavioral health.

PMID- 30201668
TI  - Depression Screening Rates and Symptom Severity by Alcohol Use Among Primary Care
      Adult Patients.
AB  - BACKGROUND: Hazardous alcohol use with depression may exacerbate health
      conditions and complicate medical care. We examined the rate of depression
      screening by alcohol use severity among primary care patients screened for
      hazardous alcohol use and, among those screened, examined patterns of significant
      depressive symptoms. METHODS: Using cross-sectional data from primary care
      patients (n = 2,894,906), we examined past-90-day alcohol use (number of typical
      drinking days/week and typical number of drinks consumed daily); depression
      screening rates (using the Patient Health Questionnaire 9 [PHQ-9]); and symptom
      severity, demographics, and prevalence of selected psychiatric diagnoses.
      RESULTS: Within 30 days of routine, in-clinic alcohol use screening by medical
      assistants, 2.4% (n = 68,686) of patients also completed a PHQ-9; these patients
      were more likely to be female, younger, white, Medicaid insured, and to have a
      nondepressive psychiatric diagnosis and a lower Charlson comorbidity score.
      Abstainers and moderate drinkers (1 to 7 drinks/week or 1 to 4 drinks/week for
      women and individuals >65 years or for men <=65 years, respectively) were less
      likely than hazardous drinkers (exceeding weekly limits) to complete the PHQ-9 or
      to have significant depressive symptoms (PHQ-9 score >=10). Nonwhite patients
      with higher Charlson comorbidity scores were more likely to endorse significant
      depressive symptoms. CONCLUSIONS: Only a small fraction of patients in this
      cohort were screened for depression. Nonwhite patients and those with higher
      comorbidity burden were more likely to report depression but less likely to be
      screened. These discrepancies between depression-screening rates and significant
      depressive symptoms suggest that screening for depression should be enhanced in
      these at-risk groups.

PMID- 30201669
TI  - How Is Family Medicine Engaging Patients at the Practice-Level?: A National
      Sample of Family Physicians.
AB  - INTRODUCTION: Emerging policy consensus advocates that patient-centered care
      should include an active, practice-level patient role, but it is unknown how
      commonly these roles are implemented. We sought to understand current prevalence
      and predictors of practice-level patient engagement in US primary care settings.
      METHODS: We assessed practice-level patient engagement by using 2016 American
      Board of Family Medicine Certification Examination registration data, restricted
      to ambulatory primary care site respondents randomly selected for a patient
      centered medical home (PCMH) question module. Multivariate logistic regression
      models identified predictors of high-intensity patient engagement, defined as a
      patient advisory council or patient volunteers in quality improvement activities.
      RESULTS: A total of 6900 examinees reported practicing in primary care sites;
      1368 randomly received PCMH questions. Practice-level patient engagement included
      patient surveys (76.5%; 95% CI, 74.3-78.8%), patient suggestion boxes (52.9%; 95%
      CI, 50.2-55.5%), patient board of director memberships (18.8%; 95% CI, 16.7
      20.9%), patient advisory councils (23.8%; 95% CI, 21.5-26.0%), and patient
      participation in quality improvement (20.5%; 95% CI, 18.3-22.6%). High-intensity
      patient engagement was reported by 31.1% (95% CI, 28.7-33.6%); predictors
      included large practice size (OR, 3.30; 95% CI, 1.96-5.57), serving more
      vulnerable patient populations, (OR, 1.83; 95% CI, 1.18-2.84) and PCMH
      certification (OR, 2.19; 95% CI, 1.62-2.97). CONCLUSIONS: Nearly one-third of
      physicians reported working in settings with high-intensity practice-level
      patient engagement. An implementation science approach should examine why high
      intensity activities are more common in some practice settings and whether these
      activities add value through improved patient experience and health outcomes.

PMID- 30201671
TI  - Medication Adherence Improvement Similar for Shared Decision-Making Preference or
      Longer Patient-Provider Relationship.
AB  - BACKGROUND: While increasing evidence supports the beneficial effects of shared
      decision making (SDM) on patient outcomes, the mechanisms underlying this
      relationship is unclear. This study evaluated length of the patient-provider
      relationship as one potential factor that may explain how SDM affects medication
      adherence in patients with hypertension. METHODS: An observational study of 75
      hypertensive patients and 27 providers in 3 primary care practices in New York
      City. A single-item measure assessed patients' preferences for decision-making
      style at baseline; medication adherence was collected over the 3-month study with
      an electronic monitoring device. Length of the relationship was measured as the
      number of years with the provider, and dichotomized as less than or greater than
      1 year with the provider. Two generalized linear mixed models were conducted to
      determine whether the SDM-adherence association was modified by length of the
      relationship. RESULTS: Most patients were Black and women, and 64% were seeing
      the same provider >1 year. Providers were mostly White women and have been at the
      clinic for 6 years. In the main-effects model, patients were more likely to
      exhibit better adherence when they preferred shared and active decision-making
      styles as compared with those who preferred a passive style (B = 15.87 [Standard
      Error [SE]: 6.62], P = .02; and B = 22.58 [SE:7.62], P = .004, respectively). In
      Model 2, the relative importance of SDM on adherence decreased as years with the
      provider increased (t(48) = 2.13; P = .04). CONCLUSION: The benefits of SDM over
      passive decision making on medication adherence were reduced with increasing
      years of the patient-provider relationship. Having an established relationship
      with the provider may have a positive impact on medication adherence that is
      comparable to relationships high in SDM.

PMID- 30201670
TI  - The Role of Gender in Cost-Related Medication Nonadherence Among Patients with
      Diabetes.
AB  - OBJECTIVE: Under 50% of type 2 diabetic patients achieve the recommended glycemic
      control. One barrier to glycemic control is patients' cost-related nonadherence
      to medications. We hypothesize gender differences in medication nonadherence due
      to costs among diabetic patients. METHODS: US National Health Interview Survey
      (2011 to 2014) data yielded 5260 males and 6188 females with diabetes for over a
      year. We applied 2 analytic methods (A and B below) across multiple outcome
      measures (1 to 4) of medication nonadherence due to cost. The key independent
      variable was participant's gender. RESULTS: Across methods and measure, females
      consistently report significantly higher rates of medication nonadherence due to
      costs. Pearson's chi2 showed that female patients were more likely to (1) skip
      medication (13.5%-10.2%; P < .001), take less than prescribed medication (13.9%
      10.5%; P < .001), delay filling prescriptions (16.8%-12.5%; P < .001), and ask
      doctors to prescribe lower-cost alternative medications (31.8%-28.0%; P < .001).
      Controlling for covariates, logistic regression models found females more likely
      to skip medication (OR, 1.30; 95% CI, 1.09-1.55), take less than prescribed
      medication (OR, 1.26; 95%, CI, 1.06-1.50), delay filling prescriptions, (OR,
      1.29; 95% CI, 1.11-1.50), and request lower-cost medication (OR, 1.17; 95% CI,
      1.04-1.32). Our results report other factors that influence medication adherence,
      including socioeconomic and health status variables. CONCLUSIONS: A significant
      gender-based disparity exists on cost-related nonadherence of medication among
      diabetic patients. Health care providers and policy-makers should pay close
      attention to find ways to address cost-related nonadherence of medication among
      patients with chronic illness, especially among female patients.

PMID- 30201672
TI  - Opioid and Drug Prevalence in Top 40's Music: A 30 Year Review.
AB  - OBJECTIVES/HYPOTHESIS: Our objective was to identify current trends in the prose
      of popular music and, specifically, to identify if a relationship exists between
      the mention of opioid narcotics in Top 40's music and a rising prevalence of
      opioid use disorder in the United States. METHODS: A list of Billboard's top 100
      songs for each year of the past 30 years (1986 to 2016) was collected. Lyrics
      from the 40 most popular songs of each year were queried for reference to drugs
      and alcohol. chi2 analysis was used to identify statistically significant
      relationships with a level of significance set at P < .05. RESULTS: There was a
      statistically significant increase in the lyrical mention to opioids (0.0% to
      5.0% of songs, P = .004), marijuana (0.6% to 17.2% of songs, P < .001), and
      alcohol (3.1% to 23.6% of songs, P < .001) in the 2010s decade when compared with
      the songs analyzed in the 1980s. The mention of opioid drugs and medications
      emerged in the late 1990s, and since, 57.1% of opioid-referencing songs mention
      prescription opioid medications and not heroin or street slang reference of the
      drug. Male- and female-driven mentions to drugs and alcohol have approached near
      equal rates in recent years. CONCLUSION: There is increasing prevalence in the
      lyrical mention of opioids, among other drugs, in Top 40's music. Nearly 50% of
      2016 Top 40's songs reference drugs or alcohol. Further inquiry may be warranted
      to evaluate the societal impact and persuasive abilities of popular culture,
      including Top 40's music, on American drug and alcohol use.

PMID- 30201673
TI  - Epidural Analgesia and Any Vaginal Laceration.
AB  - BACKGROUND: Studies have shown increased incidence of severe vaginal lacerations
      (third and fourth degree) in women under the influence of epidural analgesia.
      This increase has been attributed to the increased the use of operative vaginal
      delivery (OVD), with attendant increased risk of laceration. Although mild and
      moderate vaginal lacerations requiring suturing are clinically significant, their
      relationship to epidural analgesia has not been extensively studied. OBJECTIVE:
      The purpose of this study is to examine relationships between epidural analgesia
      in laboring women and vaginal lacerations at delivery. Our research addresses the
      question: "Is epidural analgesia in labor associated with reduced likelihood of
      vaginal laceration at delivery, compared with delivery without epidural
      analgesia? In addition, is there a difference in vaginal laceration rates between
      an urban hospital staffed by obstetricians and a suburban hospital staffed mainly
      by family physicians?" STUDY DESIGN: For the purposes of our study we included
      mild and severe perineal lacerations (first through fourth degree). We included
      all-term singleton vaginal deliveries at Truman Medical Centers Hospital Hill and
      Lakewood during 2013. We conducted a retrospective chart review that included
      2131 women. We examined the relationship of OVD to epidural and to laceration.
      Since the 2 hospitals had different characteristics, we also examined the
      relationship of location of delivery to laceration. We controlled for maternal
      age, birth weight, location of delivery, OVD, parity, and race. We examined these
      factors using a logistic regression analysis. RESULTS: After controlling for all
      factors mentioned above, epidural was negatively associated with laceration (odd
      ratio [OR], 0.886; 95% CL, 0.665, 0.991). Other factors negatively associated
      with laceration included black race, parity, and delivery at Truman Medical
      Center Lakewood (TMCLW). CONCLUSIONS: Patients who received epidural analgesia
      experienced fewer vaginal lacerations. There was no increase in OVD in patients
      who received epidural analgesia. Patients who delivered at a suburban hospital
      staffed by family medicine residents experienced fewer lacerations than those
      delivering at an urban hospital staffed by Obstetrics and Gynecology residents
      after controlling for race and other factors.

PMID- 30201675
TI  - Novel Exercises for Restless Legs Syndrome: A Randomized, Controlled Trial.
AB  - BACKGROUND: Restless legs syndrome (RLS) is a sensorimotor disorder that can have
      a considerable negative impact on quality of life and sleep. Management is
      primarily pharmacological; nonpharmacological options are limited. The objective
      of the present study was to determine the effect of tension and trauma release
      exercises on RLS severity compared with discussion group controls. METHODS:
      Participants satisfied RLS diagnostic criteria, did not have acute mental health
      conditions, and reported being physically able to complete exercises. Eighteen
      participants (stratified by age and RLS severity) were randomly allocated with
      concealment to once-weekly sessions of trauma release exercises (n = 9),
      exercises to stretch and fatigue lower limb muscles and invoke therapeutic
      tremors, or control discussion groups (n = 9) for 6 weeks. Outcomes assessed at
      baseline and each week were International Restless Legs Syndrome Rating Scale
      scores, global RLS severity ratings (visual analog scale, 0 to 10), global stress
      ratings (visual analog scale, 0 to 10), Pittsburgh Insomnia Rating Scale scores
      and Major Depression Inventory scores. RESULTS: There were no significant between
      group differences at baseline except for more severe global RLS scores for
      controls (P = .003). There were no significant between-group differences at week
      6 on any outcome. Significant improvements across time were seen for both groups
      on all outcomes. CONCLUSIONS: In this exploratory study, tension and trauma
      release exercises and attending discussion groups were associated with similar
      outcomes. Participants in both groups improved similarly across time. Future
      research might establish score stability across a prolonged baseline before
      commencing intervention.

PMID- 30201674
TI  - If We Don't Ask, They Won't Tell: Screening for Urinary and Fecal Incontinence by
      Primary Care Providers.
AB  - BACKGROUND: More than half of older adults experience urinary (UI) or fecal
      incontinence (FI), but the majority have never discussed symptoms with health
      care providers. Little is known about primary care providers' (PCPs') screening
      for UI and FI. METHODS: We conducted a cross-sectional electronic survey of PCPs
      within a Midwest academic institution to ascertain and compare PCPs' beliefs,
      attitudes, and behaviors regarding screening and treatment for UI and FI;
      determine factors associated with screening for FI; and identify potential
      barriers to and facilitators of FI screening and treatment. RESULTS: Among 154
      PCPs, the screening rate for UI (75%) was more than double that for FI (35%; P <
      .001). PCPs believed that both UI and FI screening were important but felt better
      informed to treat UI (P < .001). Screening for FI was associated with UI
      screening (OR, 11.27; 95% CI, 4.9-26.0; P < .001); feeling informed to treat FI
      (OR, 10.21; 95% CI, 1.2-90.0; P = .01); screening verbally (OR, 3.9; 95% CI, 1.9
      8.0; P < .001); perceiving screening as important (OR, 3.7; 95% CI, 1.8-7.4; P <
      .001); using the term, "accidental bowel leakage" (OR, 2.9; 95% CI, 1.2-6.7; P =
      .02) or "bowel control issues" (OR, 2.2; 95% CI, 1.1-4.5; P = .03); and being a
      resident (OR, 0.37; 95% CI, 0.16-0.82; P = .02). PCPs reported high interest in
      patient and provider educational materials about UI and FI. CONCLUSIONS: Most
      PCPs screen for UI but not FI. High reported interest in educational materials,
      coupled with high reported rates of perceived importance of screening for UI and
      FI, suggests that PCPs welcome informative interventions to streamline diagnosis
      and treatment.

PMID- 30201676
TI  - Improving Effective Magnetic Resonance Imaging (MRI) Application in Soft Tissue
      Wrist Injury.
AB  - INTRODUCTION: Magnetic resonance imaging (MRI) for soft-tissue wrist injury may
      be overprescribed, contributing to ineffective health care resource use. We aimed
      to discern predictive factors that may improve MRI's application in soft-tissue
      wrist injury. METHODS: We conducted a retrospective chart review of adults who
      underwent MRIs for possible soft-tissue wrist injury between June 2009 and June
      2014. Clinical data and treatment recommendations before and after MRI were
      analyzed. If the MRI-directed treatment recommendation was different from before
      MRI, the MRI was noted to have influenced the patient's treatment (Impact MRI).
      RESULTS: Among 140 MRI scans, 39 (28%) impacted treatment recommendation. Twenty
      six Impact MRIs were ordered by hand surgeons, whereas 13 were ordered by
      referring physicians (P = .001). More Impact MRIs were found when an MRI was
      ordered for patients younger than 36 years (P = .01), within 6 weeks of symptom
      onset (P = .03), to question a specific anatomic injury (P = .0001), or by a
      board-certified hand surgeon (P = .001). Adjusting for other covariates, these 4
      clinical factors were identified as independent predictive factors to Impact
      MRIs. CONCLUSIONS: MRIs for soft-tissue wrist injuries may more likely change
      management when the patient is younger, ordered within 6 weeks of symptom onset,
      and prescribed with a specific differential diagnosis. Referral to a hand surgeon
      should be considered before wrist MRI for the following patients: history of hand
      surgery/trauma, older than 36 years likely due to confounding chronic wrist
      changes, symptomatic for more than 6 weeks, and without clear differential
      diagnoses for the symptoms.

PMID- 30201678
TI  - Edema from Taking Cinnamon for Treatment of Diabetes: Similar Biochemistry and
      Pathophysiology to Thiazolidinedione Medications.
AB  - We present a report of cinnamon bark powder 1000 mg daily associated with edema
      that resolved after stopping the supplement in an adult male. Thiazolidinediones
      (TZDs) cause fluid retention in those with diabetes or prediabetes. Some
      medications in this class have been implicated in increased cardiac deaths from
      this side effect. While medications are effective for diabetes, many people have
      turned to natural remedies to treat their diabetes instead of conventional
      pharmaceuticals. Cinnamon is a common agent used, and it has received extensive
      lay press attention. Chemically, cinnamon bark powder activates peroxisome
      proliferated activated receptors similar to TZDs. It is reasonable to hypothesize
      that cinnamon bark powder can cause edema. This case demonstrates that cinnamon
      bark powder may have a similar side effect profile. Physicians should be aware
      that consumption of cinnamon bark powder could cause fluid retention and possibly
      worsen congestive heart failure.

PMID- 30201677
TI  - Lack of Communication about Medical Marijuana Use between Doctors and Their
      Patients.
AB  - INTRODUCTION: Medical marijuana is now permitted in most states, but it is not
      clear whether primary care physicians (PCPs) are aware of or recommend its use in
      their patients. METHODS: We distributed paired surveys to PCPs and their patients
      to assess the frequency of patient marijuana use and communication with PCPs
      about use. RESULTS: Of 242 patients surveyed, 22% reported marijuana use in the
      past 6 months, and 61% of these identified as medical marijuana users. PCPs did
      not complete state forms to recommend medical marijuana for any of the surveyed
      medical marijuana users. PCPs were aware of marijuana use in their patients only
      53% of the time. PCPs identified conditions they believed could be adversely
      affected by marijuana use in 31% of users. CONCLUSION: There is poor
      communication between patients and PCPs about medical marijuana use, which is
      being sanctioned by physicians other than patients' PCPs. We suggest more
      frequent assessment of and discussion about marijuana use in patients,
      particularly in states that have approved medical marijuana.

PMID- 30201679
TI  - Effectiveness of Clinical Decision Support Based Intervention in the Improvement
      of Care for Adult Sickle Cell Disease Patients in Primary Care.
AB  - INTRODUCTION: Although most patients with rare diseases like sickle cell disease
      (SCD) are treated in the primary care setting, primary care physicians may find
      it challenging to keep abreast of medication improvements and complications
      associated with treatment for rare and complex diseases. The purpose of this
      study was to evaluate the effectiveness of a clinical decision support (CDS) 
      based intervention system for transfusional iron overload in adults with SCD to
      improve management in primary care. METHODS: An electronic medical record based
      clinical decision support system for potential transfusional iron overload in SCD
      patients in primary care was evaluated. The intervention was implemented in 3
      family medicine clinics with a control group of 3 general internal medicine
      clinics. Data were collected in the 6 months before the intervention and 6 months
      after the intervention. There were 47 patients in the family medicine group and
      24 in the general internal medicine group. RESULTS: There was no management
      change in the control group while the intervention group improved primary care
      management from 0% to 44% (P < .001). CONCLUSION: A CDS tool can improve
      management of SCD patients in primary care.

PMID- 30201680
TI  - Interruption and Reversal of Direct Oral Anticoagulants in Preprocedural and
      Acute Settings.
AB  - With increasing physician and patient awareness, the use of direct oral
      anticoagulants (DOACs) has been steadily increasing in recent years.
      Unfortunately, given their recent introduction, the reversal of anticoagulation
      attained with DOACs is not well studied. Given the diverse mechanisms of action
      of these newer agents, no universal antidote is available for reversal.
      Laboratory assays that can accurately quantify the anticoagulation status of
      patients on DOAC therapy are not readily available, which presents a challenge in
      situations demanding rapid reversal. Furthermore, the safety and efficacy of
      reversal agents have not been extensively investigated in the clinical
      setting.This review briefly summarizes commercially available DOACs, delineates
      current knowledge related to reversal of DOAC agents in specific clinical
      settings, and identifies areas of future study.

PMID- 30201681
TI  - Re: Evaluation of an Ongoing Diabetes Group Medical Visit in a Family Medicine
      Practice.

PMID- 30201682
TI  - Re: Wide Gap between Preparation and Scope of Practice of Early Career Family
      Physicians.

PMID- 30201683
TI  - Novel Mechanism of Foxo1 Phosphorylation in Glucagon Signaling in Control of
      Glucose Homeostasis.
AB  - Dysregulation of hepatic glucose production (HGP) serves as a major underlying
      mechanism for the pathogenesis of type 2 diabetes. The pancreatic hormone
      glucagon increases and insulin suppresses HGP, controlling blood glucose
      homeostasis. The forkhead transcription factor Foxo1 promotes HGP through
      increasing expression of genes encoding the rate-limiting enzymes responsible for
      gluconeogenesis. We previously established that insulin suppresses Foxo1 by Akt
      mediated phosphorylation of Foxo1 at Ser256 in human hepatocytes. In this study,
      we found a novel Foxo1 regulatory mechanism by glucagon, which promotes Foxo1
      nuclear translocation and stability via cAMP- and protein kinase A-dependent
      phosphorylation of Foxo1 at Ser276 Replacing Foxo1-S276 with alanine (A) or
      aspartate (D) to block or mimic phosphorylation, respectively, markedly regulates
      Foxo1 stability and nuclear localization in human hepatocytes. To establish in
      vivo function of Foxo1-Ser276 phosphorylation in glucose metabolism, we generated
      Foxo1-S273A and Foxo1-S273D knock-in (KI) mice. The KI mice displayed impaired
      blood glucose homeostasis, as well as the basal and glucagon-mediated HGP in
      hepatocytes. Thus, Foxo1-Ser276 is a new target site identified in the control of
      Foxo1 bioactivity and associated metabolic diseases.

PMID- 30201684
TI  - H19 lncRNA Promotes Skeletal Muscle Insulin Sensitivity in Part by Targeting
      AMPK.
AB  - Skeletal muscle plays a pivotal role in regulating systemic glucose homeostasis
      in part through the conserved cellular energy sensor AMPK. AMPK activation
      increases glucose uptake, lipid oxidation, and mitochondrial biogenesis, leading
      to enhanced muscle insulin sensitivity and whole-body energy metabolism. Here we
      show that the muscle-enriched H19 long noncoding RNA (lncRNA) acts to enhance
      muscle insulin sensitivity, at least in part, by activating AMPK. We identify the
      atypical dual-specificity phosphatase DUSP27/DUPD1 as a potentially important
      downstream effector of H19. We show that DUSP27, which is highly expressed in
      muscle with previously unknown physiological function, interacts with and
      activates AMPK in muscle cells. Consistent with decreased H19 expression in the
      muscle of insulin-resistant human subjects and rodents, mice with genetic H19
      ablation exhibit muscle insulin resistance. Furthermore, a high-fat diet
      downregulates muscle H19 via both posttranscriptional and epigenetic mechanisms.
      Our results uncover an evolutionarily conserved, highly expressed lncRNA as an
      important regulator of muscle insulin sensitivity.

PMID- 30201685
TI  - Regulation of energy metabolism during early mammalian development: TEAD4
      controls mitochondrial transcription.
AB  - Early mammalian development is crucially dependent on the establishment of
      oxidative energy metabolism within the trophectoderm (TE) lineage. Unlike the
      inner cell mass, TE cells enhance ATP production via mitochondrial oxidative
      phosphorylation (OXPHOS) and this metabolic preference is essential for
      blastocyst maturation. However, molecular mechanisms that regulate establishment
      of oxidative energy metabolism in TE cells are incompletely understood. Here, we
      show that conserved transcription factor TEAD4, which is essential for pre
      implantation mammalian development, regulates this process by promoting
      mitochondrial transcription. In developing mouse TE and TE-derived trophoblast
      stem cells (TSCs), TEAD4 localizes to mitochondria, binds to mitochondrial DNA
      (mtDNA) and facilitates its transcription by recruiting mitochondrial RNA
      polymerase (POLRMT). Loss of TEAD4 impairs recruitment of POLRMT, resulting in
      reduced expression of mtDNA-encoded electron transport chain components, thereby
      inhibiting oxidative energy metabolism. Our studies identify a novel TEAD4
      dependent molecular mechanism that regulates energy metabolism in the TE lineage
      to ensure mammalian development.

PMID- 30201686
TI  - Lineage tracing of axial progenitors using Nkx1-2CreERT2 mice defines their trunk
      and tail contributions.
AB  - The vertebrate body forms by continuous generation of new tissue from progenitors
      at the posterior end of the embryo. The study of these axial progenitors has
      proved to be challenging in vivo largely because of the lack of unique molecular
      markers to identify them. Here, we elucidate the expression pattern of the
      transcription factor Nkx1-2 in the mouse embryo and show that it identifies axial
      progenitors throughout body axis elongation, including neuromesodermal
      progenitors and early neural and mesodermal progenitors. We create a tamoxifen
      inducible Nkx1-2CreERT2 transgenic mouse and exploit the conditional nature of
      this line to uncover the lineage contributions of Nkx1-2-expressing cells at
      specific stages. We show that early Nkx1-2-expressing epiblast cells contribute
      to all three germ layers, mostly neuroectoderm and mesoderm, excluding notochord.
      Our data are consistent with the presence of some self-renewing axial progenitors
      that continue to generate neural and mesoderm tissues from the tail bud. This
      study identifies Nkx1-2-expressing cells as the source of most trunk and tail
      tissues in the mouse and provides a useful tool to genetically label and
      manipulate axial progenitors in vivo.

PMID- 30201687
TI  - A non-canonical role for the proneural gene Neurog1 as a negative regulator of
      neocortical neurogenesis.
AB  - Neural progenitors undergo temporal identity transitions to sequentially generate
      the neuronal and glial cells that make up the mature brain. Proneural genes have
      well-characterised roles in promoting neural cell differentiation and subtype
      specification, but they also regulate the timing of identity transitions through
      poorly understood mechanisms. Here, we investigated how the highly related
      proneural genes Neurog1 and Neurog2 interact to control the timing of neocortical
      neurogenesis. We found that Neurog1 acts in an atypical fashion as it is required
      to suppress rather than promote neuronal differentiation in early corticogenesis.
      In Neurog1-/- neocortices, early born neurons differentiate in excess, whereas,
      in vitro, Neurog1-/- progenitors have a decreased propensity to proliferate and
      form neurospheres. Instead, Neurog1-/- progenitors preferentially generate
      neurons, a phenotype restricted to the Neurog2 + progenitor pool.
      Mechanistically, Neurog1 and Neurog2 heterodimerise, and while Neurog1 and
      Neurog2 individually promote neurogenesis, misexpression together blocks this
      effect. Finally, Neurog1 is also required to induce the expression of neurogenic
      factors (Dll1 and Hes5) and to repress the expression of neuronal differentiation
      genes (Fezf2 and Neurod6). Neurog1 thus employs different mechanisms to temper
      the pace of early neocortical neurogenesis.

PMID- 30201688
TI  - Use of CRISPR/Cas9 technology efficiently targetted goat myostatin through
      zygotes microinjection resulting in double-muscled phenotype in goats.
AB  - Myostatin gene (MSTN) can inhibit the proliferation of myoblast, which in turn
      promotes muscle growth and inhibits adipocyte differentiation in livestock. MSTN
      mutation may lead to muscle hypertrophy or double-muscled (DM) phenotype. MSTN
      mutation animal, such as sheep, dog, and rabbit have been generated through
      CRISPR/Cas9 technology. However, goats with promising MSTN mutation have not been
      generated. We designed two sgRNAs loci targetting exon3 of MSTN gene to destroy
      the MSTN cysteines knots. We got seven goats from seven recipients, in which six
      were MSTN knocked-out (KO) goats, with a mutation rate of 85.7%. Destroyed
      cysteine knots caused MSTN structure inactivation. The average body weight gain
      (BWG) per day of MSTN KO goats was significantly higher than that of wild-type
      (WT) goats. MSTN KO goats showed abnormal sugar, fat, and protein metabolism
      compared with wild-type controls (MSTN+/+). Inheritance of mutations was observed
      in offspring of MSTN KO goats by PCR analysis.

PMID- 30201690
TI  - Analysis of miRNA signature differentially expressed in exosomes from adriamycin
      resistant and parental human breast cancer cells.
AB  - A major cause of failure in chemotherapy is drug resistance of cancer cells.
      Exosomes have been introduced to spread chemoresistance through delivering
      miRNAs. However, a systematic evaluation of the exosomal miRNA expression
      profiles responsible for chemoresistance is still lacking. In the present study,
      miRNA signature differentially expressed in exosomes derived from adriamycin
      resistant (A/exo) and parental breast cancer cells (S/exo) were analyzed by
      microarray and the results were confirmed by PCR. A total of 309 miRNAs were
      increased and 66 miRNAs were decreased significantly in A/exo compared with
      S/exo. Specifically, 52 novel miRNAs with increased expression levels >16.0-fold
      in A/exo were identified. After prediction of target genes for 13 of 52 selected
      novel miRNAs, pathway analysis, gene ontology (GO) terms, and protein-protein
      interactions (PPIs) were constructed. The results implied that these selected
      exosomal miRNAs inhibited target genes involved in transcriptional misregulation
      in cancer, MAPK, and Wnt signaling pathways. Functional enrichment analysis
      demonstrated that the target genes were mainly responsible for protein
      phosphorylation, transcription regulation, molecular binding, and kinase
      activity. In summary, the current bioinformatics study of exosomal miRNAs may
      offer a new understanding into mechanisms of chemoresistance, which is helpful to
      find potential exosomal miRNAs to overcome drug insensitivity in future breast
      cancer treatment.

PMID- 30201691
TI  - Short-term immunogenicity of standard and accelerated hepatitis B virus
      vaccination schedules in healthy adults: a comparative field study in China.
AB  - World Health Organization recommends hepatitis B virus (HBV) immunization at 0,
      1, and 6 months. However, studies have suggested that shortening the interval
      between the first and last HBV immunization can improve completion rates. Less
      clear is whether accelerated immunization is as immunogenic as standard
      immunization. Thus, the present study aimed to compare the short-term
      immunogenicity of yeast-derived hepatitis B vaccine in healthy adults immunized
      on an accelerated or standard schedule. Between June 2013 and March 2014,
      individuals from Jinfeng and Longmen, China were randomly assigned to receive the
      vaccine on an accelerated schedule (at 0, 1, and 2 months; n=201) or a standard
      schedule (at 0, 1, and 6 months; n=206). Subjects filled out a questionnaire
      asking about demographic and other health data, and they underwent physical
      examination. Blood was assayed for HBV surface antigen and HBV surface antibody
      (HBsAb) at 1-2 months after the three-dose schedule. Multivariate binary logistic
      regression was used to determine whether the rate of anti-HBs seroconversion
      differed with immunization schedule. Covariance analysis was used to compare
      geometric mean HBsAb concentration between the two schedules. The anti-HBs
      seroconversion rate was 84.6% in the accelerated group and 90.3% in the standard
      group. After controlling for several potential confounders, the accelerated
      schedule was associated with significantly lower anti-HBs seroconversion rate
      (OR: 0.560, 95% CI: 0.318-0.988). Similarly, the accelerated schedule was
      associated with significantly lower geometric mean HBsAb concentration. These
      results suggest that the standard schedule is more likely to lead to anti-HBs
      seroconversion and higher HBsAb levels in adults.

PMID- 30201692
TI  - A novel chlorination-induced ribonuclease YabJ from Staphylococcus aureus.
AB  - The characteristic fold of a protein is the decisive factor for its biological
      function. However, small structural changes to amino acids can also affect their
      function, for example in the case of post-translational modification (PTM). Many
      different types of PTMs are known, but for some, including chlorination, studies
      elucidating their importance are limited. A recent study revealed that the
      YjgF/YER057c/UK114 family (YjgF family) member RidA from Escherichia coli shows
      chaperone activity after chlorination. Thus, to identify the functional and
      structural differences of RidA upon chlorination, we studied an RidA homolog from
      Staphylococcus aureus: YabJ. The overall structure of S. aureus YabJ was similar
      to other members of the YjgF family, showing deep pockets on its surface, and the
      residues composing the pockets were well conserved. S. aureus YabJ was highly
      stable after chlorination, and the chlorinated state is reversible by treatment
      with DTT. However, it shows no chaperone activity after chlorination. Instead,
      YabJ from S. aureus shows chlorination-induced ribonuclease activity, and the
      activity is diminished after subsequent reduction. Even though the yabJ genes
      from Staphylococcus and Bacillus are clustered with regulators that are expected
      to code nucleic acid-interacting proteins, the nucleic acid-related activity of
      bacterial RidA has not been identified before. From our study, we revealed the
      structure and function of S. aureus YabJ as a novel chlorination-activated
      ribonuclease. The present study will contribute to an in-depth understanding of
      chlorination as a PTM.

PMID- 30201689
TI  - Insights into the respiratory chain and oxidative stress.
AB  - Reactive oxygen species (ROS) are highly reactive reduced oxygen molecules that
      result from aerobic metabolism. The common forms are the superoxide anion (O2 ?-)
      and hydrogen peroxide (H2O2) and their derived forms, hydroxyl radical (HO?) and
      hydroperoxyl radical (HOO?). Their production sites in mitochondria are reviewed.
      Even though being highly toxic products, ROS seem important in transducing
      information from dysfunctional mitochondria. Evidences of signal transduction
      mediated by ROS in mitochondrial deficiency contexts are then presented in
      different organisms such as yeast, mammals or photosynthetic organisms.

PMID- 30201693
TI  - Complement is a rat natural resistance factor to amoebic liver infection.
AB  - Amoebiasis is a parasitic disease caused by Entamoeba histolytica This illness is
      prevalent in poor countries causing 100,000 deaths worldwide. Knowledge of the
      natural resistance mechanisms of rats to amoebic liver abscess (ALA) development
      may help to discover new pathogenic factors and to design novel therapeutic
      strategies against amoebiasis. In this work, histologic analyses suggested that
      the complement system may play a central role in rat natural resistance to ALA.
      E. histolytica trophozoites disappeared from rat liver within 6 h post-infection
      with minimal or no inflammatory infiltrate. In vitro findings indicate that rat
      complement was lethal for the parasite. Furthermore, hamsters became resistant to
      ALA by intravenous administration of fresh rat serum before infection. The
      amoebicidal potency of rat complement was 10 times higher than hamster complement
      and was not related to their respective CH50 levels. The alternative pathway of
      complement plays a central role in its toxicity to E. histolytica since trypan
      blue, which is a C3b receptor inhibitor, blocks its amoebicidal activity. These
      results suggest that amoebic membrane affinity, high for C3b and/or low for
      Factor H, in comparison with the hamster ones, may result in higher deposition of
      membrane complex attack on parasite surface and death.

PMID- 30201694
TI  - Huayu Tongmai Granules protects against vascular endothelial dysfunction via up
      regulating miR-185 and down-regulating RAGE.
AB  - Objective: Receptor of advanced glycation end products (RAGE) is a membrane
      protein that contributes to the initiation and progression of diabetic vascular
      complications, which is reported as a target of miR-185. Huayu Tongmai Granules
      is a Chinese herbal compound that is capable of treating diabetic angiopathy. The
      present study was designed to explore the molecular biological mechanism by which
      Huayu Tongmai Granules protects against diabetic angiopathy.Methods: The rat
      model of diabetes and hyperglucose cell model were established. The blood glucose
      was detected to verify whether the model was successfully established. Besides,
      serum nitric oxide (NO) and reactive oxygen species (ROS) concentrations of the
      rats in each group were determined. The quantitative real-time PCR analysis was
      performed to examine the mRNA expression levels of miR-185 and other miRNAs in
      femoral artery of rats or human umbilical vein endothelial cell line.
      Additionally, the protein levels of RAGE or Bax were determined using Western
      blotting. Cell apoptosis was determined by terminal dUTP nick-end labeling assay
      or flow cytometry.Results: In the present study, we found that Huayu Tongmai
      Granules significantly decreased blood glucose and serum ROS and up-regulated
      serum NO concentration. MiR-185 was low-expressed in diabetic rats; however,
      Huayu Tongmai Granules intervention up-regulated miR-185. Stable overexpression
      of miR-185 directly suppressed the expression of RAGE and further suppressed
      endothelial cell apoptosis.Conclusion: Huayu Tongmai Granules appears to have a
      therapeutic effect on diabetic angiopathy that is most probably mediated by miR
      185/RAGE axis.

PMID- 30201696
TI  - NHS staff get online service to voice concerns about working conditions.

PMID- 30201695
TI  - Troponins in scuba divers with immersion pulmonary edema.
AB  - Immersion pulmonary edema (IPE) is a serious complication of water immersion
      during scuba diving. Myocardial ischemia can occur during IPE that worsens
      outcome. Because myocardial injury impacts the therapeutic management, we aim to
      evaluate the profile of cardiac markers (creatine phosphokinase (CPK), brain
      natriuretic peptide (BNP), highly sensitive troponin T (TnT-hs) and
      ultrasensitive troponin I (TnI-us) of divers with IPE. Twelve male scuba divers
      admitted for suspected IPE were included. The collection of blood samples was
      performed at hospital entrance (T0) and 6 h later (T0 + 6 h). Diagnosis was
      confirmed by echocardiography or computed-tomography scan. Mean +/- S.D. BNP
      (pg/ml) was 348 +/- 324 at T0 and 223 +/- 177 at T0 + 6 h (P<0.01), while mean
      CPK (international units (IUs)), and mean TnT-hs (pg/ml) increased in the same
      times 238 +/- 200 compared with 545 +/- 39, (P=0.008) and 128 +/- 42 compared
      with 269 +/- 210, (P=0.01), respectively; no significant change was observed
      concerning TnI-us (pg/ml): 110 +/- 34 compared with 330 +/- 77, P=0.12. At T0 + 6
      h, three patients had high TnI-us, while six patients had high TnT-hs. Mean CPK
      was correlated with TnT-hs but not with TnI-us. Coronary angiographies were
      normal. The increase in TnT during IPE may be secondary to the release of
      troponin from non-cardiac origin. The measurement of TnI in place of TnT permits
      in some cases to avoid additional examinations, especially unnecessary invasive
      investigations.

PMID- 30201698
TI  - Espinoza JL, Elbadry MI, Chonabayashi K, et al. Hematopoiesis by iPSC-derived
      hematopoietic stem cells of aplastic anemia that escape cytotoxic T-cell attack.
      Blood Adv. 2018;2(4):390-400.

PMID- 30201697
TI  - Pre-pregnancy body mass index and breastfeeding initiation, early cessation and
      longevity: evidence from the first wave of the UK Millennium Cohort Study.
AB  - BACKGROUND: International evidence indicates relationships between pre-pregnancy
      body mass index (BMI) and breastfeeding behaviours. This study aims to assess
      associations between key points in the breastfeeding trajectory (initiation,
      early cessation and longevity) and pre-pregnancy BMI in a recent, nationally
      representative British cohort. It also aims to explore in the British context
      potential moderation by mothers' ethnic group. METHODS: The sample comprises 17
      113 mothers from the UK Millennium Cohort Study who have information on pre
      pregnancy BMI. Associations between pre-pregnancy BMI categories and
      breastfeeding initiation, early cessation and longevity are tested using logistic
      regression. Directed acyclic graphics identify appropriate minimal adjustment to
      block biasing pathways and classify total and direct effects. RESULTS: After
      adjusting for confounders, there are large differences in breastfeeding early
      cessation and longevity by pre-pregnancy BMI group. Differences in propensity to
      initiation are negligible. Having begun breastfeeding, overweight and obese
      mothers are more likely to cease in the first week and less likely to continue
      past 4 months. Observed potential mediators within pregnancy and delivery provide
      little explanation for relationships. Evidence for moderation by ethnicity is
      scant. CONCLUSIONS: The causal mechanisms underlying relationships between pre
      pregnancy overweight, obesity, and breastfeeding behaviours require further
      research. However, this study suggests pre-pregnancy BMI as one predictive
      measure for targeting support to women less likely to establish breastfeeding in
      the early days, and to continue beyond 4 months. The nature of support should
      carefully be considered and developed, with mind to both intended and potential
      unintended consequences of intervention given the need for additional
      investigation into the causes of associations.

PMID- 30201700
TI  - Histophilus somni Survives in Bovine Macrophages by Interfering with Phagosome
      Lysosome Fusion but Requires IbpA for Optimal Serum Resistance.
AB  - Histophilus somni is capable of intracellular survival within professional
      phagocytic cells, but the mechanism of survival is not understood. The Fic motif
      within the direct repeat (DR1)/DR2 domains of the IbpA fibrillary network protein
      of H. somni is cytotoxic to epithelial and phagocytic cells, which may interfere
      with the bactericidal activity of these cells. To determine the contribution of
      IbpA and Fic to resistance to host defenses, H. somni strains and mutants that
      lacked all or a region of ibpA (including the DR1/DR2 regions) were tested for
      survival in bovine monocytic cells and for serum susceptibility. An H. somni
      mutant lacking IbpA, but not the DR1/DR2 region within ibpA, was more susceptible
      to killing by antiserum than the parent, indicating that the entire protein was
      associated with serum resistance. H. somni strains expressing IbpA replicated in
      bovine monocytes for at least 72 h and were toxic for these cells. Virulent
      strain 2336 mutants lacking the entire ibpA gene or both DR1 and DR2 were not
      toxic to the monocytes but still survived within the monocytes for at least 72 h.
      Monitoring of intracellular trafficking of H. somni with monoclonal antibodies to
      phagosomal markers indicated that the early phagosomal marker early endosome
      antigen 1 colocalized with all isolates tested, but only strains that could
      survive intracellularly did not colocalize with the late lysosomal marker
      lysosome-associated membrane protein 2 and prevented the acidification of
      phagosomes. These results indicated that virulent isolates of H. somni were
      capable of surviving within phagocytic cells through interference in phagosome
      lysosome maturation. Therefore, H. somni may be considered a permissive
      intracellular pathogen.

PMID- 30201699
TI  - Bovine Staphylococcus aureus Superantigens Stimulate the Entire T Cell Repertoire
      of Cattle.
AB  - Superantigens (SAgs) represent a diverse family of bacterial toxins that induce
      Vbeta-specific T cell proliferation associated with an array of important
      diseases in humans and animals, including mastitis of dairy cows. However, an
      understanding of the diversity and distribution of SAg genes among bovine
      Staphylococcus aureus strains and their role in the pathogenesis of mastitis is
      lacking. Population genomic analysis of 195 bovine S. aureus isolates
      representing 57 unique sequence types revealed that strains encode 2 to 13
      distinct SAgs and that the majority of isolates contain 5 or more SAg genes. A
      genome-scale analysis of bovine reference strain RF122 revealed a complement of
      11 predicted SAg genes, which were all expressed in vitro Detection of specific
      antibodies in convalescent cows suggests expression of 7 of 11 SAgs during
      natural S. aureus infection. We determined the Vbeta T cell activation profile
      for all functional SAgs encoded by RF122, revealing evidence for bovine host
      specific activity among the recently identified RF122-encoded SAgs SElY and SElZ.
      Remarkably, we discovered that some strains have evolved the capacity to
      stimulate the entire T cell repertoire of cattle through an array of diverse
      SAgs, suggesting a key role in bovine immune evasion.

PMID- 30201703
TI  - Haemorrhagic complications during lumbar puncture.

PMID- 30201702
TI  - Limited Pulmonary Mucosal-Associated Invariant T Cell Accumulation and Activation
      during Mycobacterium tuberculosis Infection in Rhesus Macaques.
AB  - Mucosal-associated invariant T cells (MAITs) are positioned in airways and may be
      important in the pulmonary cellular immune response against Mycobacterium
      tuberculosis infection, particularly prior to priming of peptide-specific T
      cells. Accordingly, there is interest in the possibility that boosting MAITs
      through tuberculosis (TB) vaccination may enhance protection, but MAIT responses
      in the lungs during tuberculosis are poorly understood. In this study, we
      compared pulmonary MAIT and peptide-specific CD4 T cell responses in M.
      tuberculosis-infected rhesus macaques using 5-OP-RU-loaded MR-1 tetramers and
      intracellular cytokine staining of CD4 T cells following restimulation with an M.
      tuberculosis-derived epitope megapool (MTB300), respectively. Two of four animals
      showed a detectable increase in the number of MAIT cells in airways at later time
      points following infection, but by ~3 weeks postexposure, MTB300-specific CD4 T
      cells arrived in the airways and greatly outnumbered MAITs thereafter. In
      granulomas, MTB300-specific CD4 T cells were ~20-fold more abundant than MAITs.
      CD69 expression on MAITs correlated with tissue residency rather than bacterial
      loads, and the few MAITs found in granulomas poorly expressed granzyme B and
      Ki67. Thus, MAIT accumulation in the airways is variable and late, and MAITs
      display little evidence of activation in granulomas during tuberculosis in rhesus
      macaques.

PMID- 30201701
TI  - YraP Contributes to Cell Envelope Integrity and Virulence of Salmonella enterica
      Serovar Typhimurium.
AB  - Mutations in sigmaE-regulated lipoproteins have previously been shown to impact
      bacterial viability under conditions of stress and during in vivo infection. YraP
      is conserved across a number of Gram-negative pathogens, including Neisseria
      meningitidis, where the homolog is a component of the Bexsero meningococcal group
      B vaccine. Investigations using laboratory-adapted Escherichia coli K-12 have
      shown that yraP mutants have elevated sensitivity to a range of compounds,
      including detergents and normally ineffective antibiotics. In this study, we
      investigate the role of the outer membrane lipoprotein YraP in the pathogenesis
      of Salmonella enterica serovar Typhimurium. We show that mutations in S
      Typhimurium yraP result in a defective outer membrane barrier with elevated
      sensitivity to a range of compounds. This defect is associated with attenuated
      virulence in an oral infection model and during the early stages of systemic
      infection. We show that this attenuation is not a result of defects in
      lipopolysaccharide and O-antigen synthesis, changes in outer membrane protein
      levels, or the ability to adhere to and invade eukaryotic cell lines in vitro.

PMID- 30201704
TI  - High nitrous oxide fluxes from rice indicate the need to manage water for both
      long- and short-term climate impacts.
AB  - Global rice cultivation is estimated to account for 2.5% of current anthropogenic
      warming because of emissions of methane (CH4), a short-lived greenhouse gas. This
      estimate assumes a widespread prevalence of continuous flooding of most rice
      fields and hence does not include emissions of nitrous oxide (N2O), a long-lived
      greenhouse gas. Based on the belief that minimizing CH4 from rice cultivation is
      always climate beneficial, current mitigation policies promote increased use of
      intermittent flooding. However, results from five intermittently flooded rice
      farms across three agroecological regions in India indicate that N2O emissions
      per hectare can be three times higher (33 kg-N2O?ha-1?season-1) than the maximum
      previously reported. Correlations between N2O emissions and management parameters
      suggest that N2O emissions from rice across the Indian subcontinent might be 30
      45 times higher under intensified use of intermittent flooding than under
      continuous flooding. Our data further indicate that comanagement of water with
      inorganic nitrogen and/or organic matter inputs can decrease climate impacts
      caused by greenhouse gas emissions up to 90% and nitrogen management might not be
      central to N2O reduction. An understanding of climate benefits/drawbacks over
      time of different flooding regimes because of differences in N2O and CH4
      emissions can help select the most climate-friendly water management regimes for
      a given area. Region-specific studies of rice farming practices that map flooding
      regimes and measure effects of multiple comanaged variables on N2O and CH4
      emissions are necessary to determine and minimize the climate impacts of rice
      cultivation over both the short term and long term.

PMID- 30201705
TI  - Universal method for robust detection of circadian state from gene expression.
AB  - Circadian clocks play a key role in regulating a vast array of biological
      processes, with significant implications for human health. Accurate assessment of
      physiological time using transcriptional biomarkers found in human blood can
      significantly improve diagnosis of circadian disorders and optimize the delivery
      time of therapeutic treatments. To be useful, such a test must be accurate,
      minimally burdensome to the patient, and readily generalizable to new data. A
      major obstacle in development of gene expression biomarker tests is the diversity
      of measurement platforms and the inherent variability of the data, often
      resulting in predictors that perform well in the original datasets but cannot be
      universally applied to new samples collected in other settings. Here, we
      introduce TimeSignature, an algorithm that robustly infers circadian time from
      gene expression. We demonstrate its application in data from three independent
      studies using distinct microarrays and further validate it against a new set of
      samples profiled by RNA-sequencing. Our results show that TimeSignature is more
      accurate and efficient than competing methods, estimating circadian time to
      within 2 h for the majority of samples. Importantly, we demonstrate that once
      trained on data from a single study, the resulting predictor can be universally
      applied to yield highly accurate results in new data from other studies
      independent of differences in study population, patient protocol, or assay
      platform without renormalizing the data or retraining. This feature is unique
      among expression-based predictors and addresses a major challenge in the
      development of generalizable, clinically useful tests.

PMID- 30201706
TI  - Describing strong correlation with fractional-spin correction in density
      functional theory.
AB  - An effective fractional-spin correction is developed to describe static/strong
      correlation in density functional theory. Combined with the fractional-charge
      correction from recently developed localized orbital scaling correction (LOSC), a
      functional, the fractional-spin LOSC (FSLOSC), is proposed. FSLOSC, a correction
      to commonly used functional approximations, introduces the explicit derivative
      discontinuity and largely restores the flat-plane behavior of electronic energy
      at fractional charges and fractional spins. In addition to improving results from
      conventional functionals for the prediction of ionization potentials, electron
      affinities, quasiparticle spectra, and reaction barrier heights, FSLOSC properly
      describes the dissociation of ionic species, single bonds, and multiple bonds
      without breaking space or spin symmetry and corrects the spurious fractional
      charge dissociation of heteroatom molecules of conventional functionals. Thus,
      FSLOSC demonstrates success in reducing delocalization error and including strong
      correlation, within low-cost density functional approximation.

PMID- 30201707
TI  - Nucleosomes inhibit target cleavage by CRISPR-Cas9 in vivo.
AB  - Genome editing with CRISPR-Cas nucleases has been applied successfully to a wide
      range of cells and organisms. There is, however, considerable variation in the
      efficiency of cleavage and outcomes at different genomic targets, even within the
      same cell type. Some of this variability is likely due to the inherent quality of
      the interaction between the guide RNA and the target sequence, but some may also
      reflect the relative accessibility of the target. We investigated the influence
      of chromatin structure, particularly the presence or absence of nucleosomes, on
      cleavage by the Streptococcus pyogenes Cas9 protein. At multiple target sequences
      in two promoters in the yeast genome, we find that Cas9 cleavage is strongly
      inhibited when the DNA target is within a nucleosome. This inhibition is relieved
      when nucleosomes are depleted. Remarkably, the same is not true of zinc-finger
      nucleases (ZFNs), which cleave equally well at nucleosome-occupied and nucleosome
      depleted sites. These results have implications for the choice of specific
      targets for genome editing, both in research and in clinical and other practical
      applications.

PMID- 30201708
TI  - Predicting human behavior toward members of different social groups.
AB  - Disparities in outcomes across social groups pervade human societies and are of
      central interest to the social sciences. How people treat others is known to
      depend on a multitude of factors (e.g., others' gender, ethnicity, appearance)
      even when these should be irrelevant. However, despite substantial progress, much
      remains unknown regarding (i) the set of mechanisms shaping people's behavior
      toward members of different social groups and (ii) the extent to which these
      mechanisms can explain the structure of existing societal disparities. Here, we
      show in a set of experiments the important interplay between social perception
      and social valuation processes in explaining how people treat members of
      different social groups. Building on the idea that stereotypes can be organized
      onto basic, underlying dimensions, we first found using laboratory economic games
      that quantitative variation in stereotypes about different groups' warmth and
      competence translated meaningfully into resource allocation behavior toward those
      groups. Computational modeling further revealed that these effects operated via
      the interaction of social perception and social valuation processes, with warmth
      and competence exerting diverging effects on participants' preferences for
      equitable distributions of resources. This framework successfully predicted
      behavior toward members of a diverse set of social groups across samples and
      successfully generalized to predict societal disparities documented in labor and
      education settings with substantial precision and accuracy. Together, these
      results highlight a common set of mechanisms linking social group information to
      social treatment and show how preexisting, societally shared assumptions about
      different social groups can produce and reinforce societal disparities.

PMID- 30201710
TI  - Papaverine and its derivatives radiosensitize solid tumors by inhibiting
      mitochondrial metabolism.
AB  - Tumor hypoxia reduces the effectiveness of radiation therapy by limiting the
      biologically effective dose. An acute increase in tumor oxygenation before
      radiation treatment should therefore significantly improve the tumor cell kill
      after radiation. Efforts to increase oxygen delivery to the tumor have not shown
      positive clinical results. Here we show that targeting mitochondrial respiration
      results in a significant reduction of the tumor cells' demand for oxygen, leading
      to increased tumor oxygenation and radiation response. We identified an activity
      of the FDA-approved drug papaverine as an inhibitor of mitochondrial complex I.
      We also provide genetic evidence that papaverine's complex I inhibition is
      directly responsible for increased oxygenation and enhanced radiation response.
      Furthermore, we describe derivatives of papaverine that have the potential to
      become clinical radiosensitizers with potentially fewer side effects.
      Importantly, this radiosensitizing strategy will not sensitize well-oxygenated
      normal tissue, thereby increasing the therapeutic index of radiotherapy.

PMID- 30201709
TI  - Tissue plasminogen activator promotes white matter integrity and functional
      recovery in a murine model of traumatic brain injury.
AB  - Recombinant tissue plasminogen activator (tPA) is a Food and Drug Administration
      approved thrombolytic treatment for ischemic stroke. tPA is also naturally
      expressed in glial and neuronal cells of the brain, where it promotes axon
      outgrowth and synaptic plasticity. However, there are conflicting reports of
      harmful versus neuroprotective effects of tPA in acute brain injury models.
      Furthermore, its impact on white matter integrity in preclinical traumatic brain
      injury (TBI) has not been thoroughly explored, although white matter disruption
      is a better predictor of long-term clinical outcomes than focal lesion volumes.
      Here we show that the absence of endogenous tPA in knockout mice impedes long
      term recovery of white matter and neurological function after TBI. tPA-knockout
      mice exhibited greater asymmetries in forepaw use, poorer sensorimotor balance
      and coordination, and inferior spatial learning and memory up to 35 d after TBI.
      White matter damage was also more prominent in tPA knockouts, as shown by
      diffusion tensor imaging, histological criteria, and electrophysiological
      assessments of axon conduction properties. Replenishment of tPA through
      intranasal application of the recombinant protein in tPA-knockout mice enhanced
      neurological function, the structural and functional integrity of white matter,
      and postinjury compensatory sprouting in corticofugal projections. tPA also
      promoted neurite outgrowth in vitro, partly through the epidermal growth factor
      receptor. Both endogenous and exogenous tPA protected against white matter injury
      after TBI without increasing intracerebral hemorrhage volumes. These results
      unveil a previously unappreciated role for tPA in the protection and/or repair of
      white matter and long-term functional recovery after TBI.

PMID- 30201711
TI  - Cross-cultural invariances in the architecture of shame.
AB  - Human foragers are obligately group-living, and their high dependence on mutual
      aid is believed to have characterized our species' social evolution. It was
      therefore a central adaptive problem for our ancestors to avoid damaging the
      willingness of other group members to render them assistance. Cognitively, this
      requires a predictive map of the degree to which others would devalue the
      individual based on each of various possible acts. With such a map, an individual
      can avoid socially costly behaviors by anticipating how much audience devaluation
      a potential action (e.g., stealing) would cause and weigh this against the
      action's direct payoff (e.g., acquiring). The shame system manifests all of the
      functional properties required to solve this adaptive problem, with the aversive
      intensity of shame encoding the social cost. Previous data from three
      Western(ized) societies indicated that the shame evoked when the individual
      anticipates committing various acts closely tracks the magnitude of devaluation
      expressed by audiences in response to those acts. Here we report data supporting
      the broader claim that shame is a basic part of human biology. We conducted an
      experiment among 899 participants in 15 small-scale communities scattered around
      the world. Despite widely varying languages, cultures, and subsistence modes,
      shame in each community closely tracked the devaluation of local audiences (mean
      r = +0.84). The fact that the same pattern is encountered in such mutually remote
      communities suggests that shame's match to audience devaluation is a design
      feature crafted by selection and not a product of cultural contact or convergent
      cultural evolution.

PMID- 30201712
TI  - Interferon stimulation creates chromatin marks and establishes transcriptional
      memory.
AB  - Epigenetic memory for signal-dependent transcription has remained elusive. So
      far, the concept of epigenetic memory has been largely limited to cell
      autonomous, preprogrammed processes such as development and metabolism. Here we
      show that IFNbeta stimulation creates transcriptional memory in fibroblasts,
      conferring faster and greater transcription upon restimulation. The memory was
      inherited through multiple cell divisions and led to improved antiviral
      protection. Of ~2,000 IFNbeta-stimulated genes (ISGs), about half exhibited
      memory, which we define as memory ISGs. The rest, designated nonmemory ISGs, did
      not show memory. Surprisingly, mechanistic analysis showed that IFN memory was
      not due to enhanced IFN signaling or retention of transcription factors on the
      ISGs. We demonstrated that this memory was attributed to accelerated recruitment
      of RNA polymerase II and transcription/chromatin factors, which coincided with
      acquisition of the histone H3.3 and H3K36me3 chromatin marks on memory ISGs.
      Similar memory was observed in bone marrow macrophages after IFNgamma
      stimulation, suggesting that IFN stimulation modifies the shape of the innate
      immune response. Together, external signals can establish epigenetic memory in
      mammalian cells that imparts lasting adaptive performance upon various somatic
      cells.

PMID- 30201713
TI  - The brain's hemodynamic response function rapidly changes under acute
      psychosocial stress in association with genetic and endocrine stress response
      markers.
AB  - Ample evidence links dysregulation of the stress response to the risk for
      psychiatric disorders. However, we lack an integrated understanding of mechanisms
      that are adaptive during the acute stress response but potentially pathogenic
      when dysregulated. One mechanistic link emerging from rodent studies is the
      interaction between stress effectors and neurovascular coupling, a process that
      adjusts cerebral blood flow according to local metabolic demands. Here, using
      task-related fMRI, we show that acute psychosocial stress rapidly impacts the
      peak latency of the hemodynamic response function (HRF-PL) in temporal, insular,
      and prefrontal regions in two independent cohorts of healthy humans. These
      latency effects occurred in the absence of amplitude effects and were moderated
      by regulatory genetic variants of KCNJ2, a known mediator of the effect of stress
      on vascular responsivity. Further, hippocampal HRF-PL correlated with both
      cortisol response and genetic variants that influence the transcriptional
      response to stress hormones and are associated with risk for major depression. We
      conclude that acute stress modulates hemodynamic response properties as part of
      the physiological stress response and suggest that HRF indices could serve as
      endophenotype of stress-related disorders.

PMID- 30201714
TI  - Measurement invariance explains the universal law of generalization for
      psychological perception.
AB  - The universal law of generalization describes how animals discriminate between
      alternative sensory stimuli. On an appropriate perceptual scale, the probability
      that an organism perceives two stimuli as similar typically declines
      exponentially with the difference on the perceptual scale. Exceptions often
      follow a Gaussian probability pattern rather than an exponential pattern.
      Previous explanations have been based on underlying theoretical frameworks such
      as information theory, Kolmogorov complexity, or empirical multidimensional
      scaling. This article shows that the few inevitable invariances that must apply
      to any reasonable perceptual scale provide a sufficient explanation for the
      universal exponential law of generalization. In particular, reasonable
      measurement scales of perception must be invariant to shift by a constant value,
      which by itself leads to the exponential form. Similarly, reasonable measurement
      scales of perception must be invariant to multiplication, or stretch, by a
      constant value, which leads to the conservation of the slope of discrimination
      with perceptual difference. In some cases, an additional assumption about
      exchangeability or rotation of underlying perceptual dimensions leads to a
      Gaussian pattern of discrimination, which can be understood as a special case of
      the more general exponential form. The three measurement invariances of shift,
      stretch, and rotation provide a sufficient explanation for the universally
      observed patterns of perceptual generalization. All of the additional assumptions
      and language associated with information, complexity, and empirical scaling are
      superfluous with regard to the broad patterns of perception.

PMID- 30201716
TI  - Deceptive signals and behaviors of a cleptoparasitic beetle show local adaptation
      to different host bee species.
AB  - Chemosensory signals play a key role in species recognition and mate location in
      both invertebrate and vertebrate species. Closely related species often produce
      similar but distinct signals by varying the ratios or components in pheromone
      blends to avoid interference in their communication channels and minimize cross
      attraction among congeners. However, exploitation of reproductive signals by
      predators and parasites also may provide strong selective pressure on signal
      phenotypes. For example, bolas spiders mimic the pheromones of several moth
      species to attract their prey, and parasitic blister beetle larvae, known as
      triungulins, cooperatively produce an olfactory signal that mimics the sex
      pheromone of their female host bees to attract male bees, as the first step in
      being transported by their hosts to their nests. In both cases, there is strong
      selection pressure on the host to discriminate real mates from aggressive mimics
      and, conversely, on the predator, parasite, or parasitoid to track and locally
      adapt to the evolving signals of its hosts. Here we show local adaptation of a
      beetle, Meloe franciscanus (Coleoptera: Meloidae), to the pheromone chemistry and
      mate location behavior of its hosts, two species of solitary bees in the genus
      Habropoda We report that Mfranciscanus' deceptive signal is locally host-adapted
      in its chemical composition and ratio of components, with host bees from each
      allopatric population preferring the deceptive signals of their sympatric
      parasite population. Furthermore, in different locales, the triungulin
      aggregations have adapted their perching height to the height at which local male
      bees typically patrol for females.

PMID- 30201715
TI  - Superoxide dismutase activity confers (p)ppGpp-mediated antibiotic tolerance to
      stationary-phase Pseudomonas aeruginosa.
AB  - Metabolically quiescent bacteria represent a large proportion of those in natural
      and host environments, and they are often refractory to antibiotic treatment.
      Such drug tolerance is also observed in the laboratory during stationary phase,
      when bacteria face stress and starvation-induced growth arrest. Tolerance
      requires (p)ppGpp signaling, which mediates the stress and starvation stringent
      response (SR), but the downstream effectors that confer tolerance are unclear. We
      previously demonstrated that the SR is linked to increased antioxidant defenses
      in Pseudomonas aeruginosa We now demonstrate that superoxide dismutase (SOD)
      activity is a key factor in SR-mediated multidrug tolerance in stationary-phase
      P. aeruginosa Inactivation of the SR leads to loss of SOD activity and decreased
      multidrug tolerance during stationary phase. Genetic or chemical complementation
      of SOD activity of the DeltarelA spoT mutant (DeltaSR) is sufficient to restore
      antibiotic tolerance to WT levels. Remarkably, we observe high membrane
      permeability and increased drug internalization upon ablation of SOD activity.
      Combined, our results highlight an unprecedented mode of SR-mediated multidrug
      tolerance in stationary-phase P. aeruginosa and suggest that inhibition of SOD
      activity may potentiate current antibiotics.

PMID- 30201717
TI  - The culture of social comparison.
AB  - Social comparison is one of the most ubiquitous features of human social life.
      This fundamental human tendency to look to others for information about how to
      think, feel, and behave has provided us with the ability to thrive in a highly
      complex and interconnected modern social world. Despite its prominent role,
      however, a detailed understanding of the cultural foundations of social
      comparison is lacking. The current research aims to fill this gap by showing that
      two prominent cultural dimensions, tightness-looseness and individualism
      collectivism, uniquely explain variation in social-comparison proclivity across
      individuals, situations, and cultures. We first demonstrate the yet-undocumented
      link between cultural tightness and comparison proclivity across individuals, and
      further show that perceptions of ambient tightness and interdependence are
      uniquely associated with stronger social-comparison tendencies. Next, we show
      that these associations arise across social settings and can be attributed to
      properties of the settings themselves, not solely to individual differences.
      Finally, we show that both tight and collectivistic US states show a propensity
      to engage in Google searches related to specific social-comparison emotions, but
      that the tightness-comparison link arises from a unique psychological mechanism.
      Altogether, these findings show that social comparison-a fundamental aspect of
      human cognition-is linked to cultural practices based both in prevalence and
      strength of social norms as well as the tendency to construe the self in relation
      to others.

PMID- 30201719
TI  - Profile of Dana Carroll.

PMID- 30201718
TI  - Structure-specific DNA replication-fork recognition directs helicase and
      replication restart activities of the PriA helicase.
AB  - DNA replication restart, the essential process that reinitiates prematurely
      terminated genome replication reactions, relies on exquisitely specific
      recognition of abandoned DNA replication-fork structures. The PriA DNA helicase
      mediates this process in bacteria through mechanisms that remain poorly defined.
      We report the crystal structure of a PriA/replication-fork complex, which
      resolves leading-strand duplex DNA bound to the protein. Interaction with PriA
      unpairs one end of the DNA and sequesters the 3'-most nucleotide from the nascent
      leading strand into a conserved protein pocket. Cross-linking studies reveal a
      surface on the winged-helix domain of PriA that binds to parental duplex DNA.
      Deleting the winged-helix domain alters PriA's structure-specific DNA unwinding
      properties and impairs its activity in vivo. Our observations lead to a model in
      which coordinated parental-, leading-, and lagging-strand DNA binding provide
      PriA with the structural specificity needed to act on abandoned DNA replication
      forks.

PMID- 30201720
TI  - Systematic mapping of free energy landscapes of a growing filamin domain during
      biosynthesis.
AB  - Cotranslational folding (CTF) is a fundamental molecular process that ensures
      efficient protein biosynthesis and minimizes the formation of misfolded states.
      However, the complexity of this process makes it extremely challenging to obtain
      structural characterizations of CTF pathways. Here, we correlate observations of
      translationally arrested nascent chains with those of a systematic C-terminal
      truncation strategy. We create a detailed description of chain length-dependent
      free energy landscapes associated with folding of the FLN5 filamin domain, in
      isolation and on the ribosome, and thus, quantify a substantial destabilization
      of the native structure on the ribosome. We identify and characterize two folding
      intermediates formed in isolation, including a partially folded intermediate
      associated with the isomerization of a conserved cis proline residue. The slow
      folding associated with this process raises the prospect that neighboring
      unfolded domains might accumulate and misfold during biosynthesis. We develop a
      simple model to quantify the risk of misfolding in this situation and show that
      catalysis of folding by peptidyl-prolyl isomerases is sufficient to eliminate
      this hazard.

PMID- 30201722
TI  - More security may actually make us feel less secure.

PMID- 30201721
TI  - Intermediate step of cohesin's ATPase cycle allows cohesin to entrap DNA.
AB  - Cohesin is a four-subunit ATPase in the family of structural maintenance of
      chromosomes (SMC). Cohesin promotes sister chromatid cohesion, chromosome
      condensation, DNA repair, and transcription regulation. Cohesin performs these
      functions as a DNA tether and potentially a DNA-based motor. At least one of its
      DNA binding activities involves entrapment of DNA within a lumen formed by its
      subunits. This activity can be reconstituted in vitro by incubating cohesin with
      DNA, ATP, and cohesin loader. Previously we showed that a mutant form of cohesin
      (DE-cohesin) possesses the ability to bind and tether DNA in vivo. Using in vitro
      reconstitution assays, we show that DE-cohesin can form stable complexes with DNA
      without ATP hydrolysis. We show that wild-type cohesin with ADP aluminum fluoride
      (cohesinADP/AlFx) can also form stable cohesin-DNA complexes. These results
      suggest that an intermediate nucleotide state of cohesin, likely cohesinADP-Pi,
      is capable of initially dissociating one interface between cohesin subunits to
      allow DNA entry into a cohesin lumen and subsequently interacting with the bound
      DNA to stabilize DNA entrapment. We also show that cohesinADP/AlFx binding to DNA
      is enhanced by cohesin loader, suggesting a function for loader other than
      stimulating the ATPase. Finally, we show that loader remains stably bound to
      cohesinADP/AlFx after DNA entrapment, potentially revealing a function for loader
      in tethering the second DNA substrate. These results provide important clues on
      how SMC complexes like cohesin can function as both DNA tethers and motors.

PMID- 30201723
TI  - Hunting for hematopoietic transcriptional networks.

PMID- 30201725
TI  - Improving nanopore read accuracy with the R2C2 method enables the sequencing of
      highly multiplexed full-length single-cell cDNA.
AB  - High-throughput short-read sequencing has revolutionized how transcriptomes are
      quantified and annotated. However, while Illumina short-read sequencers can be
      used to analyze entire transcriptomes down to the level of individual splicing
      events with great accuracy, they fall short of analyzing how these individual
      events are combined into complete RNA transcript isoforms. Because of this
      shortfall, long-distance information is required to complement short-read
      sequencing to analyze transcriptomes on the level of full-length RNA transcript
      isoforms. While long-read sequencing technology can provide this long-distance
      information, there are issues with both Pacific Biosciences (PacBio) and Oxford
      Nanopore Technologies (ONT) long-read sequencing technologies that prevent their
      widespread adoption. Briefly, PacBio sequencers produce low numbers of reads with
      high accuracy, while ONT sequencers produce higher numbers of reads with lower
      accuracy. Here, we introduce and validate a long-read ONT-based sequencing
      method. At the same cost, our Rolling Circle Amplification to Concatemeric
      Consensus (R2C2) method generates more accurate reads of full-length RNA
      transcript isoforms than any other available long-read sequencing method. These
      reads can then be used to generate isoform-level transcriptomes for both genome
      annotation and differential expression analysis in bulk or single-cell samples.

PMID- 30201724
TI  - Function and crystal structure of the dimeric P-loop ATPase CFD1 coordinating an
      exposed [4Fe-4S] cluster for transfer to apoproteins.
AB  - Maturation of iron-sulfur (Fe-S) proteins in eukaryotes requires complex
      machineries in mitochondria and cytosol. Initially, Fe-S clusters are assembled
      on dedicated scaffold proteins and then are trafficked to target apoproteins.
      Within the cytosolic Fe-S protein assembly (CIA) machinery, the conserved P-loop
      nucleoside triphosphatase Nbp35 performs a scaffold function. In yeast, Nbp35
      cooperates with the related Cfd1, which is evolutionary less conserved and is
      absent in plants. Here, we investigated the potential scaffold function of human
      CFD1 (NUBP2) in CFD1-depleted HeLa cells by measuring Fe-S enzyme activities or
      55Fe incorporation into Fe-S target proteins. We show that CFD1, in complex with
      NBP35 (NUBP1), performs a crucial role in the maturation of all tested cytosolic
      and nuclear Fe-S proteins, including essential ones involved in protein
      translation and DNA maintenance. CFD1 also matures iron regulatory protein 1 and
      thus is critical for cellular iron homeostasis. To better understand the scaffold
      function of CFD1-NBP35, we resolved the crystal structure of Chaetomium
      thermophilum holo-Cfd1 (ctCfd1) at 2.6-A resolution as a model Cfd1 protein.
      Importantly, two ctCfd1 monomers coordinate a bridging [4Fe-4S] cluster via two
      conserved cysteine residues. The surface-exposed topology of the cluster is
      ideally suited for both de novo assembly and facile transfer to Fe-S apoproteins
      mediated by other CIA factors. ctCfd1 specifically interacted with ATP, which
      presumably associates with a pocket near the Cfd1 dimer interface formed by the
      conserved Walker motif. In contrast, ctNbp35 preferentially bound GTP, implying
      differential regulation of the two fungal scaffold components during Fe-S cluster
      assembly and/or release.

PMID- 30201726
TI  - Getting MAD at MYC.

PMID- 30201729
TI  - Predicting voltage sensing.
AB  - New method predicts the molecular basis of membrane proteins' voltage
      sensitivity.

PMID- 30201727
TI  - Partial maintenance of organ-specific epigenetic marks during plant asexual
      reproduction leads to heritable phenotypic variation.
AB  - Plants differ from animals in their capability to easily regenerate fertile adult
      individuals from terminally differentiated cells. This unique developmental
      plasticity is commonly observed in nature, where many species can reproduce
      asexually through the ectopic initiation of organogenic or embryogenic
      developmental programs. While organ-specific epigenetic marks are not passed on
      during sexual reproduction, the fate of epigenetic marks during asexual
      reproduction and the implications for clonal progeny remain unclear. Here we
      report that organ-specific epigenetic imprints in Arabidopsis thaliana can be
      partially maintained during asexual propagation from somatic cells in which a
      zygotic program is artificially induced. The altered marks are inherited even
      over multiple rounds of sexual reproduction, becoming fixed in hybrids and
      resulting in heritable molecular and physiological phenotypes that depend on the
      identity of the founder tissue. Consequently, clonal plants display distinct
      interactions with beneficial and pathogenic microorganisms. Our results
      demonstrate how novel phenotypic variation in plants can be unlocked through
      altered inheritance of epigenetic marks upon asexual propagation.

PMID- 30201728
TI  - mRNA vaccination with charge-altering releasable transporters elicits human T
      cell responses and cures established tumors in mice.
AB  - In vivo delivery of antigen-encoding mRNA is a promising approach to personalized
      cancer treatment. The therapeutic efficacy of mRNA vaccines is contingent on safe
      and efficient gene delivery, biological stability of the mRNA, and the
      immunological properties of the vaccine. Here we describe the development and
      evaluation of a versatile and highly efficient mRNA vaccine-delivery system that
      employs charge-altering releasable transporters (CARTs) to deliver antigen-coding
      mRNA to antigen-presenting cells (APCs). We demonstrate in human peripheral blood
      mononuclear cells that CART vaccines can activate a robust antigen-specific
      immune response against mRNA-encoded viral epitopes. In an established mouse
      model, we demonstrate that CARTs preferentially target professional APCs in
      secondary lymphoid organs upon i.v. injections and target local APCs upon s.c.
      injection. Finally, we show that CARTs coformulated with mRNA and a Toll-like
      receptor ligand simultaneously transfect and activate target cells to generate an
      immune response that can treat and cure mice with large, established tumors.

PMID- 30201731
TI  - Health systems should be publicly funded and publicly provided.

PMID- 30201730
TI  - The Patient Receiving Automated Peritoneal Dialysis with Volume Overload.

PMID- 30201733
TI  - Defending evidence informed policy making from ideological attack.

PMID- 30201732
TI  - Bayesian approach to determining penetrance of pathogenic SDH variants.
AB  - BACKGROUND: Until recently, determining penetrance required large observational
      cohort studies. Data from the Exome Aggregate Consortium (ExAC) allows a Bayesian
      approach to calculate penetrance, in that population frequencies of pathogenic
      germline variants should be inversely proportional to their penetrance for
      disease. We tested this hypothesis using data from two cohorts for succinate
      dehydrogenase subunits A, B and C (SDHA-C) genetic variants associated with
      hereditary pheochromocytoma/paraganglioma (PC/PGL). METHODS: Two cohorts were 575
      unrelated Australian subjects and 1240 unrelated UK subjects, respectively, with
      PC/PGL in whom genetic testing had been performed. Penetrance of pathogenic SDHA
      C variants was calculated by comparing allelic frequencies in cases versus
      controls from ExAC (removing those variants contributed by The Cancer Genome
      Atlas). RESULTS: Pathogenic SDHA-C variants were identified in 106 subjects
      (18.4%) in cohort 1 and 317 subjects (25.6%) in cohort 2. Of 94 different
      pathogenic variants from both cohorts (seven in SDHA, 75 in SDHB and 12 in SDHC),
      13 are reported in ExAC (two in SDHA, nine in SDHB and two in SDHC) accounting
      for 21% of subjects with SDHA-C variants. Combining data from both cohorts,
      estimated lifetime disease penetrance was 22.0% (95% CI 15.2% to 30.9%) for SDHB
      variants, 8.3% (95% CI 3.5% to 18.5%) for SDHC variants and 1.7% (95% CI 0.8% to
      3.8%) for SDHA variants. CONCLUSION: Pathogenic variants in SDHB are more
      penetrant than those in SDHC and SDHA. Our findings have important implications
      for counselling and surveillance of subjects carrying these pathogenic variants.

PMID- 30201734
TI  - Incidence and risk of major heart diseases in middle-aged adults with moderate to
      severe vision impairment: a population-based cohort study.
AB  - BACKGROUND/AIM: To estimate the incidence and risk of major adverse
      cardiovascular events (MACEs), including heart failure and ischaemic heart
      disease, among middle-aged people with a visual disability (VD). METHODS: We used
      a national health insurance research database to conduct a population-based
      cohort study from 1 January 2000 to 31 December 2013. Patients with VD aged 35~65
      years were recruited. For each VD patient, five age-matched, sex-matched and
      comorbidity-matched patients were randomly selected and recruited as controls.
      Control patients had no documented disability. RESULTS: This study recruited 978
      patients with VD (mean age+/-SD, 55.1+/-7.8 years; 48.9% male) and 4677 controls.
      Compared with the same sex of the controls, women with VD had higher incidence of
      MACE 1 (7.9 vs 2.8/1000 person-years, p<0.001), MACE 2 (27.5 vs 16.9/1000 person
      years, p<0.001), MACE 3 (3.7 vs 1.4/1000 person-years, p<0.005) and MACE 4 (4.5
      vs 2.5/1000 person-years, p<0.05), and men with VD had higher incidence of MACE 1
      (4.6 vs 2.0/1000 person-years, p<0.005). Compared with the controls, patients
      with VD had lower cumulative MACE 1~MACE 4-free probabilities and had an
      independently higher risk of MACE 1~MACE 4 during the 13-year study, yielding an
      adjusted hazard ratio range of 1.31~2.75. Those persons with VD who had diabetes
      and hypertension had greater risks of MACE 1~MACE 4. CONCLUSIONS: Middle-aged
      adults with VD were at risk of MACEs. A programme for MACE prevention is
      important for middle-aged people with VD. This is especially true for women and
      for those who also have diabetes and hypertension.

PMID- 30201736
TI  - Selective Targeting of Glioblastoma with EGFRvIII/EGFR Bitargeted Chimeric
      Antigen Receptor T Cell.
AB  - The heterogeneous expression of EGFRvIII [variant III mutant of epidermal growth
      factor receptor (EGFR)] in glioblastoma has significant impact on the clinical
      response to the treatment of EGFRvIII-specific chimeric antigen receptor
      engineered T (CAR T) cells. We hypothesized that CAR T cells that could target
      both EGFRvIII and the form of EGFR expressed on tumor cells, but not EGFR on
      normal cells, would greatly improve efficacy without inducing on-target, off
      tumor toxicity. Therefore, we developed a humanized single-chain antibody, M27,
      with a single specificity that binds to an epitope found both on wild-type EGFR-
      and EGFRvIII-overexpressing tumor cells, but not EGFR-expressing normal cells,
      including primary keratinocytes, on which wild-type EGFR is highly expressed. M27
      derived CAR T cells effectively lysed EGFRvIII- or EGFR-overexpressing tumor
      cells, but showed no observable toxicity on normal cells. Inclusion of the CD137
      (4-1BB) costimulatory intracellular domain in the M27-28BBZ CAR provided CAR T
      cells with higher tumor lysis activity than when not included (as in the M27-28Z
      CAR). The growth of established EGFR- or EGFRvIII-overexpressing glioma
      xenografts was suppressed by M27-28BBZ CAR T cells as well. The growth of
      heterogeneic xenograft tumors, created by mixing EGFR- and EGFR-overexpressing
      glioblastoma cells, was also effectively inhibited by M27-28BBZ CAR T cells. The
      survival of mice in the orthotopic models was significantly prolonged after M27
      28BBZ CAR T-cell infusion. These results suggested that tumor-selective,
      bitargeted anti-EGFR/EGFRvIII CAR T cells may be a promising modality for the
      treatment of patients with EGFR/EGFRvIII-overexpressing glioblastoma. Cancer
      Immunol Res; 6(11); 1314-26. (c)2018 AACR.

PMID- 30201735
TI  - TLR Stimulation during T-cell Activation Lowers PD-1 Expression on CD8+ T Cells.
AB  - Expression of T-cell checkpoint receptors can compromise antitumor immunity.
      Blockade of these receptors, notably PD-1 and LAG-3, which become expressed
      during T-cell activation with vaccination, can improve antitumor immunity. We
      evaluated whether T-cell checkpoint expression could be separated from T-cell
      activation in the context of innate immune stimulation with TLR agonists. We
      found that ligands for TLR1/2, TLR7, and TLR9 led to a decrease in expression of
      PD-1 on antigen-activated CD8+ T cells. These effects were mediated by IL12
      released by professional antigen-presenting cells. In two separate tumor models,
      treatment with antitumor vaccines combined with TLR1/2 or TLR7 ligands induced
      antigen-specific CD8+ T cells with lower PD-1 expression and improved antitumor
      immunity. These findings highlight the role of innate immune activation during
      effector T-cell development and suggest that at least one mechanism by which
      specific TLR agonists can be strategically used as vaccine adjuvants is by
      modulating the expression of PD-1 during CD8+ T-cell activation. Cancer Immunol
      Res; 6(11); 1364-74. (c)2018 AACR.

PMID- 30201739
TI  - NHS long term plan must tackle current challenges to set realistic targets, says
      NHS Providers.

PMID- 30201737
TI  - Comparative Secretome Analyses of Human and Zoonotic Staphylococcus aureus
      Isolates CC8, CC22, and CC398.
AB  - The spread of methicillin-resistant Staphylococcus aureus (MRSA) in the
      community, hospitals and in livestock is mediated by highly diverse virulence
      factors that include secreted toxins, superantigens, enzymes and surface
      associated adhesins allowing host adaptation and colonization. Here, we combined
      proteogenomics, secretome and phenotype analyses to compare the secreted
      virulence factors in selected S. aureus isolates of the dominant human- and
      livestock-associated genetic lineages CC8, CC22, and CC398. The proteogenomic
      comparison revealed 2181 core genes and 1306 accessory genes in 18 S. aureus
      isolates reflecting the high genome diversity. Using secretome analysis, we
      identified 869 secreted proteins with 538 commons in eight isolates of CC8, CC22,
      and CC398. These include 64 predicted extracellular and 37 cell surface proteins
      that account for 82.4% of total secretome abundance. Among the top 10 most
      abundantly secreted virulence factors are the major autolysins (Atl, IsaA, Sle1,
      SAUPAN006375000), lipases and lipoteichoic acid hydrolases (Lip, Geh, LtaS),
      cytolytic toxins (Hla, Hlb, PSMbeta1) and proteases (SspB). The CC398 isolates
      showed lower secretion of cell wall proteins, but higher secretion of alpha- and
      beta-hemolysins (Hla, Hlb) which correlated with an increased Agr activity and
      strong hemolysis. CC398 strains were further characterized by lower biofilm
      formation and staphyloxanthin levels because of decreased SigB activity. Overall,
      comparative secretome analyses revealed CC8- or CC22-specific enterotoxin and Spl
      protease secretion as well as Agr- and SigB-controlled differences in exotoxin
      and surface protein secretion between human-specific and zoonotic lineages of S.
      aureus.

PMID- 30201741
TI  - How Do the Accrual Pattern and Follow-Up Duration Affect the Hazard Ratio
      Estimate When the Proportional Hazards Assumption Is Violated?

PMID- 30201738
TI  - OXA1L mutations cause mitochondrial encephalopathy and a combined oxidative
      phosphorylation defect.
AB  - OXA1, the mitochondrial member of the YidC/Alb3/Oxa1 membrane protein insertase
      family, is required for the assembly of oxidative phosphorylation complexes IV
      and V in yeast. However, depletion of human OXA1 (OXA1L) was previously reported
      to impair assembly of complexes I and V only. We report a patient presenting with
      severe encephalopathy, hypotonia and developmental delay who died at 5 years
      showing complex IV deficiency in skeletal muscle. Whole exome sequencing
      identified biallelic OXA1L variants (c.500_507dup, p.(Ser170Glnfs*18) and
      c.620G>T, p.(Cys207Phe)) that segregated with disease. Patient muscle and
      fibroblasts showed decreased OXA1L and subunits of complexes IV and V. Crucially,
      expression of wild-type human OXA1L in patient fibroblasts rescued the complex IV
      and V defects. Targeted depletion of OXA1L in human cells or Drosophila
      melanogaster caused defects in the assembly of complexes I, IV and V, consistent
      with patient data. Immunoprecipitation of OXA1L revealed the enrichment of mtDNA
      encoded subunits of complexes I, IV and V. Our data verify the pathogenicity of
      these OXA1L variants and demonstrate that OXA1L is required for the assembly of
      multiple respiratory chain complexes.

PMID- 30201740
TI  - Results from a Monocentric Long-Term Analysis of 23 Patients with Ovarian Sertoli
      Leydig Cell Tumors.
AB  - BACKGROUND: Sertoli-Leydig cell tumors (SLCTs) represent less than 0.5% of
      ovarian tumors. Because of the rarity of this tumor and its peak in frequency at
      around 25 years of age, this study aimed to describe SLCT management strategies.
      OBJECTIVE: The objective of this study was to determine the management (i.e.,
      conservative surgery and adjuvant chemotherapy) of ovarian SLCTs. RESULTS: This
      retrospective analysis included 23 patients treated for ovarian SLCTs. A
      centralized pathologic review of the tumors was conducted. Patients were referred
      to or treated in our institution for an ovarian SLCT between 1994 and 2015. The
      median age at diagnosis was 33 years (range, 4-82 years). According to the 2014
      Federation of Gynecology and Obstetrics classification, tumors were classified as
      stage Ia (n = 15: well differentiated, n = 1; of intermediate differentiation, n
      = 8; undifferentiated, n = 4; and undefined, n = 2), stage Ib (n = 1), stage Ic1
      (n = 5), stage IIb (n = 1), and stage IIIc (n = 1). Surgery was conservative in
      13 patients (Ia, n = 7; Ib, n = 1; Ic1, n = 5) and radical in 10 patients (Ia, n
      = 8; IIb, n = 1; IIIc, n = 1). Seven patients received adjuvant chemotherapy with
      a cisplatin-based regimen (Ia, n = 2; Ic1, n = 3; IIb, n = 1) or docetaxel +
      gemcitabine (IIIc, n = 1). Median follow-up was 61 months (range, 15-252 months).
      Eight patients experienced a relapse (Ia, n = 2; Ib, n = 1; Ic1, n = 3; IIb, n =
      1; IIIc, n = 1). Of these, six had at least one peritoneal carcinomatosis, and
      four died (Ic1, n = 2; IIb, n = 1; and Ia, n = 1). Two patients had a local
      relapse (one uterus and one ovary) and survived without disease after relapse
      treatment. The median time between the initial treatment and relapse was 28
      months (range 9-70). CONCLUSION: Conservative surgery was safe for patients with
      stage Ia ovarian SLCTs. The place of conservative surgery for stage Ic1 remains
      to be defined. The best chemotherapy regimen remains to be defined. IMPLICATIONS
      FOR PRACTICE: For stage Ia disease, conservative surgery (in women of
      reproductive age) was safe and effective for treating ovarian Seroli-Leydig cell
      tumors. Adjuvant chemotherapy should be proposed for stage Ia when poor
      prognostic factors are present (poor differentiation, retiform pattern, or
      heterologous elements). For stage Ic1 and more severe stages, radical surgery and
      adjuvant chemotherapy should be considered. The combination of bleomycin,
      etoposide, and cisplatin was the most frequently used regimen, but the best
      chemotherapy regimen remains to be defined.

PMID- 30201742
TI  - What's happening in Neurology(r)Clinical Practice.

PMID- 30201743
TI  - What's happening in Without Borders.

PMID- 30201744
TI  - Idiopathic intracranial hypertension: The veno glymphatic connections.
AB  - The recent discoveries of the glymphatic and lymphatic systems of the brain have
      helped advance our understanding of CSF physiology and may allow new insights in
      the understanding of idiopathic intracranial hypertension (IIH). The clinical and
      radiologic presentations of IIH appear to be related to congestion of the
      glymphatic system associated with an overflow of the lymphatic CSF outflow
      pathway. By revisiting the role of "vascular arachnoid granulations" in the
      brain, we hypothesize that an initial impairment of the transport of interstitial
      fluid from the glymphatic system to the venous blood of the dural sinuses may
      trigger the hydrodynamic cascade of IIH. Furthermore, we speculate that, similar
      to other water-exchange systems in the brain, a specific subtype of aquaporin is
      involved in this transport. This theory may eventually help to provide an
      underlying explanation for IIH and its associated conditions, since in most of
      them, the expression of several aquaporins is altered.

PMID- 30201745
TI  - Alien hand syndrome.

PMID- 30201746
TI  - Education Research: A framework for global health curricula for neurology
      trainees.
AB  - As the global burden of neurologic disease increases, educating future
      neurologists about the principles of global health through global health
      curricula is of utmost importance. However, few neurology residency training
      programs have developed and implemented comprehensive global health curricula.
      This report outlines the design, implementation, and evaluation of the University
      of Massachusetts Medical School neurology residency global health curriculum.
      Using accepted curriculum development methods and incorporating an innovative use
      of technology, we created a global health curriculum focused on neurology to
      engage trainees. The implementation of curricula and organization of elective
      opportunities also incorporates learning objectives and an evaluation process.
      The University of Massachusetts Medical School neurology global health curriculum
      can be used as a framework for other residency programs developing global health
      programs. Global health education increases young neurologists' awareness of the
      growing burden of neurologic disease and, subsequently, may motivate them to
      address the need for neurologic expertise around the world.

PMID- 30201747
TI  - Editors' note: An interdisciplinary response to contemporary concerns about brain
      death determination.

PMID- 30201748
TI  - Reader response: An interdisciplinary response to contemporary concerns about
      brain death determination.

PMID- 30201749
TI  - Reader response: An interdisciplinary response to contemporary concerns about
      brain death determination.

PMID- 30201750
TI  - Reader response: An interdisciplinary response to contemporary concerns about
      brain death determination.

PMID- 30201751
TI  - Reader response: An interdisciplinary response to contemporary concerns about
      brain death determination.

PMID- 30201753
TI  - Subcutaneous ofatumumab in patients with relapsing-remitting multiple sclerosis:
      The MIRROR study.

PMID- 30201752
TI  - Author response: An interdisciplinary response to contemporary concerns about
      brain death determination.

PMID- 30201754
TI  - Clinical Reasoning: Young adult with dysphagia and severe weight loss.

PMID- 30201755
TI  - Teaching NeuroImages: Cortical damage with leptomeningeal enhancement in
      neuromyelitis optica spectrum disorder.

PMID- 30201756
TI  - Teaching Video NeuroImages: A treatable rare cause of chorea.

PMID- 30201757
TI  - Testing and monitoring direct oral anticoagulants.
AB  - Direct oral anticoagulants (DOACs) have significantly improved the care of
      patients requiring anticoagulation. With similar or better efficacy and safety
      outcomes and easier use in the outpatient setting compared with the standard-of
      care vitamin K antagonists and low molecular weight heparin, DOACs are now
      endorsed as first-line treatment of indications including prevention of stroke
      and systemic embolism in nonvalvular atrial fibrillation and treatment of venous
      thromboembolism. DOACs are easy-to-use oral agents that offer simple dosing and
      short half-lives, with no need to test levels because of the wide therapeutic
      window and limited drug-drug interactions. After almost a decade of DOAC use, the
      question of testing DOAC levels in certain clinical situations has become the
      focus of debate. Although guidance for using routine coagulation tests is
      available, these tests are inadequate for optimal care. DOAC-specific tests have
      been developed but have limited availability in Europe and less availability in
      the United States. None are licensed. DOAC testing may be useful in the setting
      of critical clinical situations such as life-threatening bleeding or need for
      emergent surgery, especially with the availability of DOAC reversal agents.
      Patients with characteristics that fall outside the normal range may benefit from
      the guidance that DOAC testing could offer. Obstacles to adopting DOAC testing
      have been raised, such as test reliability and staffing costs; however, these
      problems are rapidly being resolved. Further investigation of the role of DOAC
      testing is needed to explore its full potential and role in clinical practice.

PMID- 30201758
TI  - Preemptive rituximab prevents long-term relapses in immune-mediated thrombotic
      thrombocytopenic purpura.
AB  - Preemptive rituximab infusions prevent relapses in immune thrombotic
      thrombocytopenic purpura (iTTP) by maintaining normal ADAMTS13 activity. However,
      the long-term outcome of these patients and the potential adverse events of this
      strategy need to be determined. We report the long-term outcome of 92 patients
      with iTTP in clinical remission who received preemptive rituximab after
      identification of severe ADAMTS13 deficiency (activity <10%) during the follow
      up. Thirty-seven patients had >1 iTTP episode, and the median cumulative relapse
      incidence before preemptive rituximab was 0.33 episode per year (interquartile
      range [IQR], 0.23-0.66). After preemptive rituximab, the median cumulative
      relapse incidence in the whole population decreased to 0 episodes per year (IQR,
      0-1.32; P < .001). After preemptive rituximab, ADAMTS13 activity recovery was
      sustained in 34 patients (37%) during a follow-up of 31.5 months (IQR, 18-65),
      and severe ADAMTS13 deficiency recurred in 45 patients (49%) after the initial
      improvement. ADAMTS13 activity usually improved with additional courses of
      preemptive rituximab. In 13 patients (14%), ADAMTS13 activity remained
      undetectable after the first rituximab course, but retreatment was efficient in 6
      of 10 cases. In total, 14 patients (15%) clinically relapsed, and 19 patients
      (20.7%) experienced benign adverse effects. Preemptive rituximab treatment was
      associated with a change in ADAMTS13 conformation in respondent patients.
      Finally, in the group of 23 historical patients with iTTP and persistently
      undetectable ADAMTS13 activity, 74% clinically relapsed after a 7-year follow-up
      (IQR, 5-11). In conclusion, persistently undetectable ADAMTS13 activity in iTTP
      during remission is associated with a higher relapse rate. Preemptive rituximab
      reduces clinical relapses by maintaining a detectable ADAMTS13 activity with an
      advantageous risk-benefit balance.

PMID- 30201760
TI  - Spatial architecture and arrangement of tumor-infiltrating lymphocytes for
      predicting likelihood of recurrence in early-stage non-small cell lung cancer.
AB  - PURPOSE: Presence of a high degree of tumor-infiltrating lymphocytes (TILs) has
      proven to be associated with outcome in patients with non-small cell lung cancer
      (NSCLC). However, recent evidence indicate that tissue architecture is also
      prognostic of disease specific survival and recurrence. We show a set of
      descriptors (SpaTIL) that capture density and spatial co-localization of TILs and
      tumor cells across digital images can predict likelihood of recurrence in early
      stage NSCLC. EXPERIMENTAL DESIGN: The association between recurrence in early
      stage NSCLC and SpaTIL features was explored on 301 patients across four
      different cohorts. Cohort D1 (n=70) was used to identify the most prognostic
      SpaTIL features and to train a classifier to predict the likelihood of
      recurrence. The classifier performance was evaluated in cohorts D2 (n=119), D3
      (n=112), and D4 (n=112). Two pathologists graded each sample of D1 and D2; intra
      observer agreement and association between manual grading and likelihood of
      recurrence were analyzed. RESULTS: SpaTIL was associated with likelihood of
      recurrence in all test sets (log rank p<0.02). A multivariate Cox Proportional
      Hazards analysis revealed a HR of 3.08 (95% confidence interval, 2.1-4.5,
      p=7.3x10-5). In contrast, agreement among expert pathologists using tumor grade
      was moderate (Kappa=0.5), and the manual TIL grading was only prognostic for one
      reader in D2 (p=8.0x10-3). CONCLUSION: A set of features related to density and
      spatial architecture of TILs was found to be associated with a likelihood of
      recurrence of early-stage NSCLC. This information could potentially be used for
      helping in treatment planning and management of early-stage NSCLC.

PMID- 30201761
TI  - A First-in-Human Study of Novel Cereblon Modulator Avadomide (CC-122) in Advanced
      Malignancies.
AB  - Purpose: Avadomide is a novel, small-molecule therapeutic agent that modulates
      cereblon E3 ligase activity and exhibits potent antitumor and immunomodulatory
      activities. This first-in-human phase I study (NCT01421524) evaluated the safety
      and clinical activity of avadomide in patients with advanced solid tumors, non
      Hodgkin lymphoma (NHL), and multiple myeloma.Experimental Design: Thirty-four
      patients were treated with avadomide in 7 dose-escalation cohorts using a 3 + 3
      design (0.5-3.5 mg, 28-day continuous dosing cycles). The primary objectives were
      to determine the dose-limiting toxicity (DLT), nontolerated dose (NTD), maximum
      tolerated dose (MTD), recommended phase II dose, and pharmacokinetics of
      avadomide. The secondary objective was to determine preliminary avadomide
      efficacy. Exploratory objectives included evaluation of pharmacodynamic effects
      of avadomide.Results: DLTs were reported in 2 patients, and grade >=3 treatment
      emergent adverse events (TEAEs) occurred in 14 patients (41%). The most common
      TEAEs (>=15%) were fatigue, neutropenia, and diarrhea. The NTD and MTD were 3.5
      and 3.0 mg, respectively. Of 5 patients with NHL, 1 achieved a complete response,
      and 2 had partial responses. Although no objective responses were observed in
      patients with solid tumors, 5 of 6 patients with brain cancer experienced
      nonprogression of >=6 months. A dose-dependent relationship between Aiolos
      degradation in peripheral B and T cells occurred within 5 hours of the first dose
      of avadomide administered, starting at 0.5 mg.Conclusions: Avadomide monotherapy
      demonstrated acceptable safety and favorable pharmacokinetics in patients with
      solid tumors, NHL, and multiple myeloma. In addition, 3 objective responses were
      observed in NHL. Clin Cancer Res; 1-9. (c)2018 AACR.

PMID- 30201759
TI  - Systems Genetics Approach to Biomarker Discovery: GPNMB and Heart Failure in Mice
      and Humans.
AB  - We describe a simple bioinformatics method for biomarker discovery that is based
      on the analysis of global transcript levels in a population of inbred mouse
      strains showing variation for disease-related traits. This method has advantages
      such as controlled environment and accessibility to heart and plasma tissue in
      the preclinical selection stage. We illustrate the approach by identifying
      candidate heart failure (HF) biomarkers by overlaying mouse transcriptome and
      clinical traits from 91 Hybrid Mouse Diversity Panel (HMDP) inbred strains and
      human HF transcriptome from the Myocardial Applied Genomics Network (MAGNet)
      consortium. We found that some of the top differentially expressed genes
      correlated with known human HF biomarkers, such as galectin-3 and tissue
      inhibitor of metalloproteinase 1. Using ELISA assays, we investigated one novel
      candidate, Glycoprotein NMB, in a mouse model of chronic beta-adrenergic
      stimulation by isoproterenol (ISO) induced HF. We observed significantly lower
      GPNMB plasma levels in the ISO model compared to the control group (p-value =
      0.007). In addition, we assessed GPNMB plasma levels among 389 HF cases and
      controls from the METabolic Syndrome In Men (METSIM) study. Lower levels of GPNMB
      were also observed in patients with HF from the METSIM study compared to non-HF
      controls (p-value < 0.0001). In summary, we have identified several candidate
      biomarkers for HF using the cardiac transcriptome data in a population of mice
      that may be directly relevant and applicable to human populations.

PMID- 30201762
TI  - Evaluation of Novel Prostate-Specific Membrane Antigen-Targeted Near-Infrared
      Imaging Agent for Fluorescence-Guided Surgery of Prostate Cancer.
AB  - Purpose: The ability to locate and remove all malignant lesions during radical
      prostatectomy leads not only to prevent biochemical recurrence (BCR) and possible
      side effects but also to improve the life expectancy of patients with prostate
      cancer. Fluorescence-guided surgery (FGS) has emerged as a technique that uses
      fluorescence to highlight cancerous cells and guide surgeons to resect tumors in
      real time. Thus, development of tumor-specific near-infrared (NIR) agents that
      target biomarkers solely expressed on prostate cancer cells will enable to assess
      negative tumor margins and affected lymph nodes.Experimental Design: Because PSMA
      is overexpressed in prostate cancer cells in >90% of the prostate cancer patient
      population, a prostate-specific membrane antigen (PSMA)-targeted NIR agent
      (OTL78) was designed and synthesized. Optical properties, in vitro and in vivo
      specificity, tumor-to-background ratio (TBR), accomplishment of negative surgical
      tumor margins using FGS, pharmacokinetics (PKs) properties, and preclinical
      toxicology of OTL78 were then evaluated in requisite models.Results: OTL78 binds
      to PSMA-expressing cells with high affinity, concentrates selectively to PSMA
      positive cancer tissues, and clears rapidly from healthy tissues with a half-time
      of 17 minutes. It also exhibits an excellent TBR (5:1) as well as safety profile
      in animals.Conclusions: OTL78 is an excellent tumor-specific NIR agent for use in
      fluorescence-guided radical prostatectomy and FGS of other cancers. Clin Cancer
      Res; 1-11. (c)2018 AACR.

PMID- 30201763
TI  - Discovery and Therapeutic Exploitation of Mechanisms of Resistance to MET
      Inhibitors in Glioblastoma.
AB  - Purpose: Glioblastoma (GBM) is the most common and most lethal primary malignant
      brain tumor. The receptor tyrosine kinase MET is frequently upregulated or
      overactivated in GBM. Although clinically applicable MET inhibitors have been
      developed, resistance to single modality anti-MET drugs frequently occurs,
      rendering these agents ineffective. We aimed to determine the mechanisms of MET
      inhibitor resistance in GBM and use the acquired information to develop novel
      therapeutic approaches to overcome resistance.Experimental Design: We
      investigated two clinically applicable MET inhibitors: crizotinib, an ATP
      competitive small molecule inhibitor of MET, and onartuzumab, a monovalent
      monoclonal antibody that binds to the extracellular domain of the MET receptor.
      We developed new MET inhibitor-resistant cells lines and animal models and used
      reverse phase protein arrays (RPPA) and functional assays to uncover the
      compensatory pathways in MET inhibitor-resistant GBM.Results: We identified
      critical proteins that were altered in MET inhibitor-resistant GBM including
      mTOR, FGFR1, EGFR, STAT3, and COX-2. Simultaneous inhibition of MET and one of
      these upregulated proteins led to increased cell death and inhibition of cell
      proliferation in resistant cells compared with either agent alone. In addition,
      in vivo treatment of mice bearing MET-resistant orthotopic xenografts with COX-2
      or FGFR pharmacological inhibitors in combination with MET inhibitor restored
      sensitivity to MET inhibition and significantly inhibited tumor
      growth.Conclusions: These data uncover the molecular basis of adaptive resistance
      to MET inhibitors and identify new FDA-approved multidrug therapeutic
      combinations that can overcome resistance. Clin Cancer Res; 1-11. (c)2018 AACR.

PMID- 30201765
TI  - Opioid-Independent and Opioid-Mediated Modes of Pain Modulation.
AB  - Pain is regulated endogenously through both opioid and non-opioid mechanisms. We
      hypothesized that two novel pain modulation tasks, one drawing on
      context/expectations and one using voluntary reappraisal, would show differing
      levels of opioid dependence. Specifically, we expected that naloxone would block
      context-related analgesia, whereas mental imagery-based pain reappraisal would be
      opioid-independent.A double-blind, placebo-controlled intravenous naloxone versus
      saline crossover design was used. Twenty healthy volunteers completed the two
      modulation tasks with acute heat stimuli calibrated to induce moderate pain. In
      the mental imagery task, participants imagined either a "pleasant" or a
      "comparison" scenario during painful heat. In the relative relief task, moderate
      heat stimuli coincided with visual cues eliciting relief from the expectation of
      intense pain, and were compared with moderate heat stimuli delivered under the
      expectation of non-painful warmth. Both "pleasant imagery" and "relative relief"
      conditions significantly improved ratings of pain intensity and pleasantness
      during saline treatment. Indeed, the target stimuli in both tasks, which had been
      calibrated to induce moderate pain, were rated as mildly pleasant. Furthermore,
      consistently with the main hypothesis, blocking endogenous opioid signaling with
      naloxone did not significantly affect imagery-induced regulation of pain
      intensity or pleasantness. In contrast, the relative relief-induced pain
      regulation (i.e., context/expectation) was blocked by naloxone. We conclude that
      endogenous opioid signaling is necessary for expectation-related relative relief
      analgesia, but not for pain reappraisal through mental imagery. These results
      support mental imagery as a powerful and clinically relevant strategy for
      regulating pain affect also in patients where endogenous opioid mechanisms might
      be compromised.SIGNIFICANCE STATEMENT Neurotransmitter systems in the human brain
      can be probed through antagonist drugs. Studies using the opioid antagonist
      naloxone have demonstrated that the brain relies on both opioid and non-opioid
      mechanisms to downregulate pain. This holds clinical relevance given altered
      endogenous opioid processes in many chronic pain conditions. The present study
      used a double-blinded, placebo-controlled naloxone blockage of endogenous opioids
      in healthy humans to show differential opioid involvement in two pain modulation
      tasks. Context/expectation-driven (relative relief-related) analgesia was blocked
      by naloxone. In contrast, pain reappraisal through mental imagery was intact
      despite opioid receptor blockade, suggesting opioid independence. These results
      support mental imagery as a powerful, clinically relevant strategy for regulating
      pain as it does not rely on a functioning opioidergic system.

PMID- 30201766
TI  - Amnesiac Is Required in the Adult Mushroom Body for Memory Formation.
AB  - It was proposed that the Drosophila amnesiac gene (amn) is required for
      consolidation of aversive memory in the dorsal paired medial (DPM) neurons, a
      pair of large neurons that broadly innervate the mushroom bodies (MB), the fly
      center for olfactory learning and memory (Waddell et al., 2000). Yet, a
      conditional analysis showed that it was not possible to rescue the memory deficit
      of amnX8 null mutant flies when amn expression was restored only in the adult
      (DeZazzo et al., 1999), which led the authors to suggest that amn might be
      involved in the development of brain structures that normally promote adult
      olfactory memory. To further investigate temporal and spatial requirements of
      Amnesiac (AMN) peptide in memory, we used RNA interference in combination with
      conditional drivers. Experiments were conducted either in both sexes, or in
      either sexes. Our data show that acute modulation of amn expression in adult DPM
      neurons does not impact memory. We further show that amn expression is required
      for normal development of DPM neurons. Detailed enhancer trap analyses suggest
      that amn transcription unit contains two distinct enhancers, one specific of DPM
      neurons, and the other specific of alpha/beta MB neurons. This prompted us to
      investigate extensively the role of AMN in the adult MB. Together, our results
      demonstrate that amn is acutely required in adult alpha/beta MB neurons for
      middle-term and long-term memory. The data thus establish that amn plays two
      distinct roles. Its expression is required in DPM neurons for their development,
      and in adult MB for olfactory memory.SIGNIFICANCE STATEMENT The Drosophila
      amnesiac gene encodes a neuropeptide whose expression was proposed to be required
      for consolidation of aversive memory in the dorsal paired medial (DPM) neurons, a
      pair of large neurons that broadly innervate the mushroom bodies (MB), the
      olfactory memory center. Here, we investigated amnesiac temporal and spatial
      requirement using conditional tools that allowed us to manipulate its expression
      in selected neurons. This work leads to a complete reassessment of the role of
      amnesiac in brain development and memory. We show that amnesiac is required for
      two distinct processes: for normal development of DPM neurons, and in adult MB
      for memory.

PMID- 30201764
TI  - Microglia Play an Active Role in Obesity-Associated Cognitive Decline.
AB  - Obesity affects >600 million people worldwide, a staggering number that appears
      to be on the rise. One of the lesser known consequences of obesity is its
      deleterious effects on cognition, which have been well documented across many
      cognitive domains and age groups. To investigate the cellular mechanisms that
      underlie obesity-associated cognitive decline, we used diet-induced obesity in
      male mice and found memory impairments along with reductions in dendritic spines,
      sites of excitatory synapses, increases in the activation of microglia, the
      brain's resident immune cells, and increases in synaptic profiles within
      microglia, in the hippocampus, a brain region linked to cognition. We found that
      partial knockdown of the receptor for fractalkine, a chemokine that can serve as
      a "find me" cue for microglia, prevented microglial activation and cognitive
      decline induced by obesity. Furthermore, we found that pharmacological inhibition
      of microglial activation in obese mice was associated with prevention of both
      dendritic spine loss and cognitive degradation. Finally, we observed that
      pharmacological blockade of microglial phagocytosis lessened obesity-associated
      cognitive decline. These findings suggest that microglia play an active role in
      obesity-associated cognitive decline by phagocytosis of synapses that are
      important for optimal function.SIGNIFICANCE STATEMENT Obesity in humans
      correlates with reduced cognitive function. To investigate the cellular
      mechanisms underlying this, we used diet-induced obesity in mice and found
      impaired performance on cognitive tests of hippocampal function. These deficits
      were accompanied by reduced numbers of dendritic spines, increased microglial
      activation, and increased synaptic profiles within microglia. Inhibition of
      microglial activation by transgenic and pharmacological methods prevented
      cognitive decline and dendritic spine loss in obese mice. Moreover,
      pharmacological inhibition of the phagocytic activity of microglia was also
      sufficient to prevent cognitive degradation. This work suggests that microglia
      may be responsible for obesity-associated cognitive decline and dendritic spine
      loss.

PMID- 30201767
TI  - Hypothalamic CCL2/CCR2 Chemokine System: Role in Sexually Dimorphic Effects of
      Maternal Ethanol Exposure on Melanin-Concentrating Hormone and Behavior in
      Adolescent Offspring.
AB  - Clinical and animal studies show that ethanol exposure and inflammation during
      pregnancy cause similar behavioral disturbances in the offspring. While ethanol
      is shown to stimulate both neuroimmune and neurochemical systems in adults,
      little is known about their anatomical relationship in response to ethanol in
      utero and whether neuroimmune factors mediate ethanol's effects on neuronal
      development and behavior in offspring. Here we examined in female and male
      adolescent rats a specific population of neurons concentrated in lateral
      hypothalamus, which coexpress the inflammatory chemokine C-C motif ligand 2
      (CCL2) or its receptor CCR2 with the orexigenic neuropeptide, melanin
      concentrating hormone (MCH), that promotes ethanol drinking behavior. We
      demonstrate that maternal administration of ethanol (2 g/kg/d) from embryonic day
      10 (E10) to E15, while having little impact on glia, stimulates expression of
      neuronal CCL2 and CCR2, increases density of both large CCL2 neurons colocalizing
      MCH and small CCL2 neurons surrounding MCH neurons, and stimulates ethanol
      drinking and anxiety in adolescent offspring. We show that these neuronal and
      behavioral changes are similarly produced by maternal administration of CCL2 (4
      or 8 MUg/kg/d, E10-E15) and blocked by maternal administration of a CCR2
      antagonist INCB3344 (1 mg/kg/d, E10-E15), and these effects of ethanol and CCL2
      are sexually dimorphic, consistently stronger in females. These results suggest
      that this neuronal CCL2/CCR2 system closely linked to MCH neurons has a role in
      mediating the effects of maternal ethanol exposure on adolescent offspring and
      contributes to the higher levels of adolescent risk factors for alcohol use
      disorders described in women.SIGNIFICANCE STATEMENT Ethanol consumption and
      inflammatory agents during pregnancy similarly increase alcohol intake and
      anxiety in adolescent offspring. To investigate how neurochemical and neuroimmune
      systems interact to mediate these disturbances, we examined a specific population
      of hypothalamic neurons coexpressing the inflammatory chemokine CCL2 and its
      receptor CCR2 with the neuropeptide, melanin-concentrating hormone. We
      demonstrate in adolescent offspring that maternal administration of CCL2, like
      ethanol, stimulates these neurons and increases ethanol drinking and anxiety, and
      these effects of ethanol are blocked by maternal CCR2 antagonist and consistently
      stronger in females. This suggests that neuronal chemokine signaling linked to
      neuropeptides mediates effects of maternal ethanol exposure on adolescent
      offspring and contributes to higher levels of adolescent risk factors for alcohol
      use disorders in women.

PMID- 30201769
TI  - TRPM2 Exacerbates Central Nervous System Inflammation in Experimental Autoimmune
      Encephalomyelitis by Increasing Production of CXCL2 Chemokines.
AB  - Multiple sclerosis (MS) is a chronic inflammatory disorder of the CNS
      characterized by demyelination and axonal injury. Current therapies that mainly
      target lymphocytes do not fully meet clinical need due to the risk of severe side
      effects and lack of efficacy against progressive MS. Evidence suggests that MS is
      associated with CNS inflammation, although the underlying molecular mechanism is
      poorly understood. Transient receptor potential melastatin 2 (TRPM2), a Ca2+
      permeable nonselective cation channel, is expressed at high levels in the brain
      and by immune cells, including monocyte lineage cells. Here, we show that TRPM2
      plays a pathological role in experimental autoimmune encephalomyelitis (EAE), an
      animal model of MS. Knockout (KO) or pharmacological inhibition of TRPM2
      inhibited progression of EAE and TRPM2-KO mice showed lower activation of Iba1
      immunopositive monocyte lineage cells and neutrophil infiltration of the CNS than
      WT mice. Moreover, CXCL2 production in TRPM2-KO mice was significantly reduced at
      day 14, although the severity of EAE was the same as that in WT mice at that time
      point. In addition, we used BM chimeric mice to show that TRPM2 expressed by CNS
      infiltrating macrophages contributes to progression of EAE. Because CXCL2 induces
      migration of neutrophils, these results indicate that reduced expression of CXCL2
      in the CNS suppresses neutrophil infiltration and slows progression of EAE in
      TRPM2-KO mice. Together, the results suggest that TRPM2 plays an important role
      in progression of EAE pathology and shed light on its putative role as a
      therapeutic target for MS.SIGNIFICANCE STATEMENT Current therapies for multiple
      sclerosis (MS), which mainly target lymphocytes, carry the risk of severe side
      effects and lack efficacy against the progressive form of the disease. Here, we
      found that the transient receptor potential melastatin 2 (TRPM2) channel, which
      is abundantly expressed in CNS-infiltrating macrophages, plays a crucial role in
      development of experimental autoimmune encephalomyelitis (EAE), an animal model
      of MS. EAE progression was suppressed by Knockout (KO) or pharmacological
      inhibition of TRPM2; this was attributed to a reduction in CXCL2 chemokine
      production by CNS-infiltrating macrophages in TRPM2-KO mice, resulting in
      suppression of neutrophil infiltration into the CNS. These results reveal an
      important role of TRPM2 in the pathogenesis of EAE and shed light on its
      potential as a therapeutic target.

PMID- 30201768
TI  - Dreaming in NREM Sleep: A High-Density EEG Study of Slow Waves and Spindles.
AB  - Dreaming can occur in both rapid eye movement (REM) and non-REM (NREM) sleep. We
      recently showed that in both REM and NREM sleep, dreaming is associated with
      local decreases in slow wave activity (SWA) in posterior brain regions. To expand
      these findings, here we asked how specific features of slow waves and spindles,
      the hallmarks of NREM sleep, relate to dream experiences. Fourteen healthy human
      subjects (10 females) underwent nocturnal high-density EEG recordings combined
      with a serial awakening paradigm. Reports of dreaming, compared with reports of
      no experience, were preceded by fewer, smaller, and shallower slow waves, and
      faster spindles, especially in central and posterior cortical areas. We also
      identified a minority of very steep and large slow waves in frontal regions,
      which occurred on a background of reduced SWA and were associated with high
      frequency power increases (local "microarousals") heralding the successful recall
      of dream content. These results suggest that the capacity of the brain to
      generate experiences during sleep is reduced in the presence of neuronal off
      states in posterior and central brain regions, and that dream recall may be
      facilitated by the intermittent activation of arousal systems during NREM
      sleep.SIGNIFICANCE STATEMENT By combining high-density EEG recordings with a
      serial awakening paradigm in healthy subjects, we show that dreaming in non-rapid
      eye movement sleep occurs when slow waves in central and posterior regions are
      sparse, small, and shallow. We also identified a small subset of very large and
      steep frontal slow waves that are associated with high-frequency activity
      increases (local "microarousals") heralding successful recall of dream content.
      These results provide noninvasive measures that could represent a useful tool to
      infer the state of consciousness during sleep.

PMID- 30201771
TI  - Spinal RNF20-Mediated Histone H2B Monoubiquitylation Regulates mGluR5
      Transcription for Neuropathic Allodynia.
AB  - To date, histone H2B monoubiquitination (H2Bub), a mark associated with
      transcriptional elongation and ongoing transcription, has not been linked to the
      development or maintenance of neuropathic pain states. Here, using male Sprague
      Dawley rats, we demonstrated spinal nerve ligation (SNL) induced behavioral
      allodynia and provoked ring finger protein 20 (RNF20)-dependent H2Bub in dorsal
      horn. Moreover, SNL provoked RNF20-mediated H2Bub phosphorylated RNA polymerase
      II (RNAPII) in the promoter fragments of mGluR5, thereby enhancing mGluR5
      transcription/expression in the dorsal horn. Conversely, focal knockdown of
      spinal RNF20 expression reversed not only SNL-induced allodynia but also
      RNF20/H2Bub/RNAPII phosphorylation-associated spinal mGluR5
      transcription/expression. Notably, TNF-alpha injection into naive rats and
      specific neutralizing antibody injection into SNL-induced allodynia rats revealed
      that TNF-alpha-associated allodynia involves the RNF20/H2Bub/RNAPII
      transcriptional axis to upregulate mGluR5 expression in the dorsal horn.
      Collectively, our findings indicated TNF-alpha induces RNF20-drived H2B
      monoubiquitination, which facilitates phosphorylated RNAPII-dependent mGluR5
      transcription in the dorsal horn for the development of neuropathic
      allodynia.SIGNIFICANCE STATEMENT Histone H2B monoubiquitination (H2Bub), an
      epigenetic post-translational modification, positively correlated with gene
      expression. Here, TNF-alpha participated in neuropathic pain development by
      enhancing RNF20-mediated H2Bub, which facilitates phosphorylated RNAPII-dependent
      mGluR5 transcription in dorsal horn. Our finding potentially identified
      neuropathic allodynia pathophysiological processes underpinning abnormal
      nociception processing and opens a new avenue for the development of novel
      analgesics.

PMID- 30201770
TI  - Cortical Potentials Evoked by Subthalamic Stimulation Demonstrate a Short Latency
      Hyperdirect Pathway in Humans.
AB  - A monosynaptic projection from the cortex to the subthalamic nucleus is thought
      to have an important role in basal ganglia function and in the mechanism of
      therapeutic subthalamic deep-brain stimulation, but in humans the evidence for
      its existence is limited. We sought physiological confirmation of the cortico
      subthalamic hyperdirect pathway using invasive recording techniques in patients
      with Parkinson's disease (9 men, 1 woman). We measured sensorimotor cortical
      evoked potentials using a temporary subdural strip electrode in response to low
      frequency deep-brain stimulation in patients undergoing awake subthalamic or
      pallidal lead implantations. Evoked potentials were grouped into very short
      latency (<2 ms), short latency (2-10 ms), and long latency (10-100 ms) from the
      onset of the stimulus pulse. Subthalamic and pallidal stimulation resulted in
      very short-latency evoked potentials at 1.5 ms in the primary motor cortex
      accompanied by EMG-evoked potentials consistent with corticospinal tract
      activation. Subthalamic, but not pallidal stimulation, resulted in three short
      latency evoked potentials at 2.8, 5.8, and 7.7 ms in a widespread cortical
      distribution, consistent with antidromic activation of the hyperdirect pathway.
      Long-latency potentials were evoked by both targets, with subthalamic responses
      lagging pallidal responses by 10-20 ms, consistent with orthodromic activation of
      the thalamocortical pathway. The amplitude of the first short-latency evoked
      potential was predictive of the chronic therapeutic stimulation
      contact.SIGNIFICANCE STATEMENT This is the first physiological demonstration of
      the corticosubthalamic hyperdirect pathway and its topography at high spatial
      resolution in humans. We studied cortical potentials evoked by deep-brain
      stimulation in patients with Parkinson's disease undergoing awake lead
      implantation surgery. Subthalamic stimulation resulted in multiple short-latency
      responses consistent with activation of hyperdirect pathway, whereas no such
      response was present during pallidal stimulation. We contrast these findings with
      very short latency, direct corticospinal tract activations, and long-latency
      responses evoked through polysynaptic orthodromic projections. These findings
      underscore the importance of incorporating the hyperdirect pathway into models of
      human basal ganglia function.

PMID- 30201772
TI  - Visuomotor Correlates of Conflict Expectation in the Context of Motor Decisions.
AB  - Many behaviors require choosing between conflicting options competing against
      each other in visuomotor areas. Such choices can benefit from top-down control
      processes engaging frontal areas in advance of conflict when it is anticipated.
      Yet, very little is known about how this proactive control system shapes the
      visuomotor competition. Here, we used electroencephalography in human subjects
      (male and female) to identify the visual and motor correlates of conflict
      expectation in a version of the Eriksen Flanker task that required left or right
      responses according to the direction of a central target arrow surrounded by
      congruent or incongruent (conflicting) flankers. Visual conflict was either
      highly expected (it occurred in 80% of trials; mostly incongruent blocks) or very
      unlikely (20% of trials; mostly congruent blocks). We evaluated selective
      attention in the visual cortex by recording target- and flanker-related steady
      state visual-evoked potentials (SSVEPs) and probed action selection by measuring
      response-locked potentials (RLPs) in the motor cortex. Conflict expectation
      enhanced accuracy in incongruent trials, but this improvement occurred at the
      cost of speed in congruent trials. Intriguingly, this behavioral adjustment
      occurred while visuomotor activity was less finely tuned: target-related SSVEPs
      were smaller while flanker-related SSVEPs were higher in mostly incongruent
      blocks than in mostly congruent blocks, and incongruent trials were associated
      with larger RLPs in the ipsilateral (nonselected) motor cortex. Hence, our data
      suggest that conflict expectation recruits control processes that augment the
      tolerance for inappropriate visuomotor activations (rather than processes that
      downregulate their amplitude), allowing for overflow activity to occur without
      having it turn into the selection of an incorrect response.SIGNIFICANCE STATEMENT
      Motor choices made in front of discordant visual information are more accurate
      when conflict can be anticipated, probably due to the engagement of top-down
      control from frontal areas. How this control system modulates activity within
      visual and motor areas is unknown. Here, we show that, when control processes are
      recruited in anticipation of conflict, as evidenced by higher midfrontal theta
      activity, visuomotor activity is less finely tuned: visual processing of the goal
      relevant location was reduced and the motor cortex displayed more inappropriate
      activations, compared with when conflict was unlikely. We argue that conflict
      expectation is associated with an expansion of the distance-to-selection
      threshold, improving accuracy while the need for online control of visuomotor
      activity is reduced.

PMID- 30201774
TI  - Neuronal Response Latencies Encode First Odor Identity Information across
      Subjects.
AB  - Odorants are coded in the primary olfactory processing centers by spatially and
      temporally distributed patterns of glomerular activity. Whereas the spatial
      distribution of odorant-induced responses is known to be conserved across
      individuals, the universality of its temporal structure is still debated. Via
      fast two-photon calcium imaging, we analyzed the early phase of neuronal
      responses in the form of the activity onset latencies in the antennal lobe
      projection neurons of honeybee foragers. We show that each odorant evokes a
      stimulus-specific response latency pattern across the glomerular coding space.
      Moreover, we investigate these early response features for the first time across
      animals, revealing that the order of glomerular firing onsets is conserved across
      individuals and allows them to reliably predict odorant identity, but not
      concentration. These results suggest that the neuronal response latencies provide
      the first available code for fast odor identification.SIGNIFICANCE STATEMENT
      Here, we studied early temporal coding in the primary olfactory processing
      centers of the honeybee brain by fast imaging of glomerular responses to
      different odorants across glomeruli and across individuals. Regarding the elusive
      role of rapid response dynamics in olfactory coding, we were able to clarify the
      following aspects: (1) the rank of glomerular activation is conserved across
      individuals, (2) its stimulus prediction accuracy is equal to that of the
      response amplitude code, and (3) it contains complementary information. Our
      findings suggest a substantial role of response latencies in odor identification,
      anticipating the static response amplitude code.

PMID- 30201773
TI  - Stac Proteins Suppress Ca2+-Dependent Inactivation of Neuronal l-type Ca2+
      Channels.
AB  - Stac protein (named for its SH3- and cysteine-rich domains) was first identified
      in brain 20 years ago and is currently known to have three isoforms. Stac2,
      Stac1, and Stac3 transcripts are found at high, modest, and very low levels,
      respectively, in the cerebellum and forebrain, but their neuronal functions have
      been little investigated. Here, we tested the effects of Stac proteins on
      neuronal, high-voltage-activated Ca2+ channels. Overexpression of the three Stac
      isoforms eliminated Ca2+-dependent inactivation (CDI) of l-type current in rat
      neonatal hippocampal neurons (sex unknown), but not CDI of non-l-type current.
      Using heterologous expression in tsA201 cells (together with beta and alpha2
      delta1 auxiliary subunits), we found that CDI for CaV1.2 and CaV1.3 (the
      predominant, neuronal l-type Ca2+ channels) was suppressed by all three Stac
      isoforms, whereas CDI for the P/Q channel, CaV2.1, was not. For CaV1.2, the
      inhibition of CDI by the Stac proteins appeared to involve their direct
      interaction with the channel's C terminus. Within the Stac proteins, a weakly
      conserved segment containing ~100 residues and linking the structurally conserved
      PKC C1 and SH3_1 domains was sufficient to fully suppress CDI. The presence of
      CDI for l-type current in control neonatal neurons raised the possibility that
      endogenous Stac levels are low in these neurons and Western blotting indicated
      that the expression of Stac2 was substantially increased in adult forebrain and
      cerebellum compared with neonate. Together, our results indicate that one likely
      function of neuronal Stac proteins is to tune Ca2+ entry via neuronal l-type
      channels.SIGNIFICANCE STATEMENT Stac protein, first identified 20 years ago in
      brain, has recently been found to be essential for proper trafficking and
      function of the skeletal muscle l-type Ca2+ channel and is the site of mutations
      causing a severe, inherited human myopathy. In neurons, however, functions for
      Stac protein have remained unexplored. Here, we report that one likely function
      of neuronal Stac proteins is tuning Ca2+ entry via l-type, but not that via non-l
      type, Ca2+ channels. Moreover, there is a large postnatal increase in protein
      levels of the major neuronal isoform (Stac2) in forebrain and cerebellum, which
      could provide developmental regulation of l-type channel Ca2+ signaling in these
      brain regions.

PMID- 30201775
TI  - Suppressing Interferon-gamma Stimulates Microglial Responses and Repair of
      Microbleeds in the Diabetic Brain.
AB  - Microcirculatory damage is a common complication for those with vascular risk
      factors, such as diabetes. To resolve vascular insults, the brain's immune cells
      (microglia) must rapidly envelop the site of injury. Currently, it is unknown
      whether Type 1 diabetes, a condition associated with chronic immune system
      dysfunction, alters microglial responses to damage and what mechanisms are
      responsible. Using in vivo two-photon microscopy in adult male mice, we show that
      microglial envelopment of laser-induced cerebral microbleeds is diminished in a
      hyperglycemic mouse model of Type 1 diabetes, which could not be fully rescued
      with chronic insulin treatment. Microglia were important for vessel repair
      because reduced microglial accumulation in diabetic mice or near-complete
      depletion in healthy controls was associated with greater secondary leakage of
      the damaged vessel. Broadly suppressing inflammation with dexamethasone in
      diabetic mice but not healthy controls, significantly enhanced microglial
      responses to microbleeds and attenuated secondary vessel leakage. These
      enhancements were associated with changes in IFN-gamma signaling because
      dexamethasone suppressed abnormally high levels of IFN-gamma protein levels in
      brain and blood serum of diabetic mice. Further, blocking IFN-gamma in diabetic
      mice with neutralizing antibodies restored normal microglial chemotaxic responses
      and purinoceptor P2ry12 gene expression, as well as mitigated secondary leakage.
      These results suggest that abnormal IFN-gamma signaling disrupts microglial
      function in the diabetic brain, and that immunotherapies targeting IFN-gamma can
      stimulate microglial repair of damaged vessels.SIGNIFICANCE STATEMENT Although
      Type 1 diabetes is an established risk factor for vascular complications, such as
      microbleeds, and is known to hinder wound healing in the body, no study has
      examined how diabetes impacts the brain's innate immune reparative response
      (involving cells called microglia) to vascular injury. Here we show that
      microglial responses to brain microbleeds were diminished in diabetic animals,
      which also exacerbated secondary leakage from damaged vessels. These impairments
      were related to abnormally high levels of the proinflammatory cytokine IFN-gamma
      because reducing IFN-gamma with immunosuppressant drugs or blocking antibodies
      helped restore normal microglial responses and repair of damaged vessels. These
      data highlight the use of IFN-gamma modulating therapeutics to enhance vascular
      repair in at-risk populations.

PMID- 30201776
TI  - Synthetic circuits reveal how mechanisms of gene regulatory networks constrain
      evolution.
AB  - Phenotypic variation is the raw material of adaptive Darwinian evolution. The
      phenotypic variation found in organismal development is biased towards certain
      phenotypes, but the molecular mechanisms behind such biases are still poorly
      understood. Gene regulatory networks have been proposed as one cause of
      constrained phenotypic variation. However, most pertinent evidence is theoretical
      rather than experimental. Here, we study evolutionary biases in two synthetic
      gene regulatory circuits expressed in Escherichia coli that produce a gene
      expression stripe-a pivotal pattern in embryonic development. The two parental
      circuits produce the same phenotype, but create it through different regulatory
      mechanisms. We show that mutations cause distinct novel phenotypes in the two
      networks and use a combination of experimental measurements, mathematical
      modelling and DNA sequencing to understand why mutations bring forth only some
      but not other novel gene expression phenotypes. Our results reveal that the
      regulatory mechanisms of networks restrict the possible phenotypic variation upon
      mutation. Consequently, seemingly equivalent networks can indeed be distinct in
      how they constrain the outcome of further evolution.

PMID- 30201778
TI  - The assembly order of flagellar rod subunits in Bacillus subtilis.
AB  - Bacterial flagella contain an axle-like rod that transits the cell envelope and
      connects the transmembrane basal body to the extracellular hook and filament.
      Although the rod is a crucial component of the flagellum, its structure and
      assembly are poorly understood. Previous reports defining the order of rod
      assembly in Gram-negative bacteria suggest that the rod requires five proteins to
      successfully assemble but assembly intermediates have not been well characterized
      due to metastablity and periplasmic proteolysis. Bacillus subtilis is a Gram
      positive, genetically tractable model bacterium that synthesizes flagella and
      lacks a true periplasm. Here we genetically, biochemically, and cytologically
      determine the assembly order of the flagellar rod from cell proximal to distal as
      FliE, FlgB, FlgC, FlhO, and FlhP. We further show under conditions in which rod
      structure cannot be completed, assembly intermediates are both metastable and
      subject to proteolysis. Finally, we support previous results that FliE serves as
      both a structural assembly platform for the rod and as an enhancer of flagellar
      type III secretion.IMPORTANCE Bacteria rotate propeller like flagella to find and
      colonize environmental niches. The flagellum is a complex machine and
      understanding of its structure is still incomplete. Here we characterize and
      biochemically define the assembly order of the subunits that make up the axle
      like rod. The rod is a critical component for the assembly of subsequent
      components and is central to our understanding of how the flagellum is anchored
      but still free spinning within the context of the cell envelope.

PMID- 30201777
TI  - Genotoxic, Metabolic, and Oxidative Stresses Regulate the RNA Repair Operon of
      Salmonella enterica Serovar Typhimurium.
AB  - The sigma54 regulon in Salmonella enterica serovar Typhimurium includes a
      predicted RNA repair operon encoding homologs of the metazoan Ro60 protein (Rsr),
      Y RNAs (YrlBA), RNA ligase (RtcB), and RNA 3'-phosphate cyclase (RtcA).
      Transcription from sigma54-dependent promoters requires that a cognate bacterial
      enhancer binding protein (bEBP) be activated by a specific environmental or
      cellular signal; the cognate bEBP for the sigma54-dependent promoter of the rsr
      yrlBA-rtcBA operon is RtcR. To identify conditions that generate the signal for
      RtcR activation in S Typhimurium, transcription of the RNA repair operon was
      assayed under multiple stress conditions that result in nucleic acid damage. RtcR
      dependent transcription was highly induced by the nucleic acid cross-linking
      agents mitomycin C (MMC) and cisplatin, and this activation was dependent on
      RecA. Deletion of rtcR or rtcB resulted in decreased cell viability relative to
      that of the wild type following treatment with MMC. Oxidative stress from
      peroxide exposure also induced RtcR-dependent transcription of the operon.
      Nitrogen limitation resulted in RtcR-independent increased expression of the
      operon; the effect of nitrogen limitation required NtrC. The adjacent toxin
      antitoxin module, dinJ-yafQ, was cotranscribed with the RNA repair operon but was
      not required for RtcR activation, although YafQ endoribonuclease activated RtcR
      dependent transcription. Stress conditions shown to induce expression the RNA
      repair operon of Escherichia coli (rtcBA) did not stimulate expression of the S
      Typhimurium RNA repair operon. Similarly, MMC did not induce expression of the E.
      coli rtcBA operon, although when expressed in S Typhimurium, E. coli RtcR
      responds effectively to the unknown signal(s) generated there by MMC
      exposure.IMPORTANCE Homologs of the metazoan RNA repair enzymes RtcB and RtcA
      occur widely in eubacteria, suggesting a selective advantage. Although the
      enzymatic activities of the eubacterial RtcB and RtcA have been well
      characterized, the physiological roles remain largely unresolved. Here we report
      stress responses that activate expression of the sigma54-dependent RNA repair
      operon (rsr-yrlBA-rtcBA) of S Typhimurium and demonstrate that expression of the
      operon impacts cell survival under MMC-induced stress. Characterization of the
      requirements for activation of this tightly regulated operon provides clues to
      the possible functions of operon components in vivo, enhancing our understanding
      of how this human pathogen copes with environmental stressors.

PMID- 30201779
TI  - Regulatory Targets of the Response Regulator RR_1586 from Clostridioides
      difficile Identified Using a Bacterial One-Hybrid Screen.
AB  - The Clostridioides difficile R20291 genome encodes 57 response regulator proteins
      that, as part of two-component signaling pathways, regulate adaptation to
      environmental conditions. Genomic and transcriptomic studies in C. difficile have
      been limited, due to technical challenges, to the analysis of either high
      throughput screens or high-priority targets, such as primary regulators of toxins
      or spore biology. We present the use of several technically accessible and
      generally applicable techniques to elucidate the putative regulatory targets of a
      response regulator, RR_1586, involved in sporulation of the hypervirulent C.
      difficile strain R20291. A DNA-binding specificity motif for RR_1586 was
      determined using a bacterial one-hybrid assay originally developed for Drosophila
      transcription factors. Comparative bioinformatics approaches identified and in
      vitro experiments confirmed RR_1586 binding sites upstream of putative target
      genes, including those that encode phosphate ion transporters,
      spermidine/putrescine biosynthesis and transport pathways, ABC type transport
      systems, known regulators of sporulation, and genes encoding spore structural
      proteins. Representative examples of these regulatory interactions have been
      tested and confirmed in Escherichia coli-based reporter assays. Finally, evidence
      of possible regulatory mechanisms is also presented. A working model includes
      self-regulation by RR_1586 and phosphorylation-dependent and -independent DNA
      binding at low- and high-fidelity binding sites, respectively. Broad application
      of this and similar approaches is anticipated to be an important catalyst for the
      study of gene regulation by two-component systems from pathogenic or technically
      challenging bacteria.IMPORTANCE Clostridioides difficile spores survive under
      harsh conditions and can germinate into actively dividing cells capable of
      causing disease. An understanding of the regulatory networks controlling
      sporulation and germination in C. difficile could be exploited for therapeutic
      advantage. However, such studies are hindered by the challenges of working with
      an anaerobic pathogen recalcitrant to genetic manipulation. Although two
      component response regulators can be identified from genetic sequences,
      identification of their downstream regulatory networks requires further
      development. This work integrates experimental and bioinformatic approaches,
      which provide practical advantages over traditional transcriptomic analyses, to
      identify the putative regulon of the C. difficile response regulator RR_1586 by
      first screening for protein-DNA interactions in E. coli and then predicting
      regulatory outputs in C. difficile.

PMID- 30201780
TI  - CovR and VicRKX Regulate Transcription of the Collagen Binding Protein Cnm of
      Streptococcus mutans.
AB  - Cnm is a surface-associated protein present in a subset of Streptococcus mutans
      strains that mediates binding to extracellular matrices, intracellular invasion,
      and virulence. Here, we showed that cnm transcription is controlled by the global
      regulators CovR and VicRKX. In silico analysis identified multiple putative CovR-
      and VicR-binding motifs in the regulatory region of cnm as well as in the
      downstream gene pgfS, which is associated with the posttranslational modification
      of Cnm. Electrophoretic mobility shift assays revealed that CovR and VicR
      specifically and independently bind to the cnm and pgfS promoter regions.
      Quantitative real-time PCR and Western blot analyses of DeltacovR and DeltavicK
      strains as well as of a strain overexpressing vicRKX revealed that CovR functions
      as a positive regulator of cnm, whereas VicRKX acts as a negative regulator. In
      agreement with the role of VicRKX as a repressor, the DeltavicK strain showed
      enhanced binding to collagen and laminin and higher intracellular invasion rates.
      Overexpression of vicRKX was associated with decreased rates of intracellular
      invasion but did not affect collagen or lamin binding activities, suggesting that
      this system controls additional genes involved in binding to these extracellular
      matrix proteins. As expected, based on the role of CovR in cnm regulation, the
      DeltacovR strain showed decreased intracellular invasion rates, but, unexpectedly
      collagen and laminin binding activities were increased in this mutant strain.
      Collectively, the results presented here expand the repertoire of virulence
      related genes regulated by CovR and VicRKX to include the core gene pgfS and the
      noncore gene cnm IMPORTANCE Streptococcus mutans is a major pathogen associated
      with dental caries and also implicated in systemic infections, in particular,
      infective endocarditis. The Cnm adhesin of S. mutans is an important virulence
      factor associated with systemic infections and caries severity. Despite its role
      in virulence, the regulatory mechanisms governing cnm expression are poorly
      understood. Here, we describe the identification of two independent regulatory
      systems controlling the transcription of cnm and the downstream pgfS-pgfM1-pgfE
      pgfM2 operon. A better understanding of the mechanisms controlling expression of
      virulence factors like Cnm can facilitate the development of new strategies to
      treat bacterial infections.

PMID- 30201781
TI  - Sinorhizobium meliloti Chemoreceptor McpV Senses Short-Chain Carboxylates via
      Direct Binding.
AB  - Sinorhizobium meliloti is a soil-dwelling endosymbiont of alfalfa that has eight
      chemoreceptors to sense environmental stimuli during its free-living state. The
      functions of two receptors have been characterized, with McpU and McpX serving as
      general amino acid and quaternary ammonium compound sensors, respectively. Both
      receptors use a dual Cache (calcium channels and chemotaxis receptors) domain for
      ligand binding. We identified that the ligand-binding periplasmic region (PR) of
      McpV contains a single Cache domain. Homology modeling revealed that McpVPR is
      structurally similar to a sensor domain of a chemoreceptor with unknown function
      from Anaeromyxobacter dehalogenans, which crystallized with acetate in its
      binding pocket. We therefore assayed McpV for carboxylate binding and S. meliloti
      for carboxylate sensing. Differential scanning fluorimetry identified 10
      potential ligands for McpVPR Nine of these are monocarboxylates with chain
      lengths between two and four carbons. We selected seven compounds for capillary
      assay analysis, which established positive chemotaxis of the S. meliloti wild
      type, with concentrations of peak attraction at 1 mM for acetate, propionate,
      pyruvate, and glycolate, and at 100 mM for formate and acetoacetate. Deletion of
      mcpV or mutation of residues essential for ligand coordination abolished positive
      chemotaxis to carboxylates. Using microcalorimetry, we determined that
      dissociation constants of the seven ligands with McpVPR were in the micromolar
      range. An McpVPR variant with a mutation in the ligand coordination site
      displayed no binding to isobutyrate or propionate. Of all the carboxylates tested
      as attractants, only glycolate was detected in alfalfa seed exudates. This work
      examines the relevance of carboxylates and their sensor to the rhizobium-legume
      interaction.IMPORTANCE Legumes share a unique association with certain soil
      dwelling bacteria known broadly as rhizobia. Through concerted interorganismal
      communication, a legume allows intracellular infection by its cognate rhizobial
      species. The plant then forms an organ, the root nodule, dedicated to housing and
      supplying fixed carbon and nutrients to the bacteria. In return, the engulfed
      rhizobia, differentiated into bacteroids, fix atmospheric N2 into ammonium for
      the plant host. This interplay is of great benefit to the cultivation of legumes,
      such as alfalfa and soybeans, and is initiated by chemotaxis to the host plant.
      This study on carboxylate chemotaxis contributes to the understanding of
      rhizobial survival and competition in the rhizosphere and aids the development of
      commercial inoculants.

PMID- 30201782
TI  - Connecting the dots between mechanosensitive channel abundance, osmotic shock,
      and survival at single-cell resolution.
AB  - Rapid changes in extracellular osmolarity are one of many insults microbial cells
      face on a daily basis. To protect against such shocks, Escherichia coli and other
      microbes express several types of transmembrane channels which open and close in
      response to changes in membrane tension. In E. coli, one of the most abundant
      channels is the mechanosensitive channel of large conductance (MscL). While this
      channel has been heavily characterized through structural methods,
      electrophysiology, and theoretical modeling, our understanding of its
      physiological role in preventing cell death by alleviating high membrane tension
      remains tenuous. In this work, we examine the contribution of MscL alone to cell
      survival after osmotic shock at single cell resolution using quantitative
      fluorescence microscopy. We conduct these experiments in an E. coli strain which
      is lacking all mechanosensitive channel genes save for MscL whose expression is
      tuned across three orders of magnitude through modifications of the Shine
      Dalgarno sequence. While theoretical models suggest that only a few MscL channels
      would be needed to alleviate even large changes in osmotic pressure, we find that
      between 500 and 700 channels per cell are needed to convey upwards of 80%
      survival. This number agrees with the average MscL copy number measured in wild
      type E. coli cells through proteomic studies and quantitative Western blotting.
      Furthermore, we observe zero survival events in cells with less than ~100
      channels per cell. This work opens new questions concerning the contribution of
      other mechanosensitive channels to survival as well as regulation of their
      activity.Importance Mechanosensitive (MS) channels are transmembrane protein
      complexes which open and close in response to changes in membrane tension as a
      result of osmotic shock. Despite extensive biophysical characterization, the
      contribution of these channels to cell survival remains largely unknown. In this
      work, we use quantitative video microscopy to measure the abundance of a single
      species of MS channel in single cells followed by their survival after a large
      osmotic shock. We observe total death of the population with less than ~100
      channels per cell and determine that approximately 500 - 700 channels are needed
      for 80% survival. The number of channels we find to confer nearly full survival
      is consistent with the counts of the number of channels in wild type cells in
      several earlier studies. These results prompt further studies to dissect the
      contribution of other channel species to survival.

PMID- 30201784
TI  - Rationing policy will do far more harm than good.

PMID- 30201785
TI  - The impact of STRICTA and CONSORT on reporting of randomised control trials of
      acupuncture: a systematic methodological evaluation.
AB  - BACKGROUND: Clear and unambiguous reporting is essential for researchers and
      clinicians to be able to assess the quality of research. To enhance the quality
      of reporting, consensus-based reporting guidelines are commonly used. OBJECTIVES:
      To update and extend previous research by evaluating the more recent impact of
      STRICTA (STandards for Reporting Interventions in Controlled Trials of
      Acupuncture) and CONSORT (CONsolidated Standards Of Reporting Trials) guidelines
      on the quality of reporting of acupuncture trials. METHODS: By random sampling,
      approximately 45 trials from each of five 2-year time periods between 1994 and
      2015 were included in the study. Using scoring sheets based on the STRICTA and
      CONSORT checklist items (range 0 to 7 and 0 to 5, respectively), the distribution
      of items reported over time was investigated, with changes shown using
      scatterplots. The primary analysis used a before-and-after t-test to compare time
      periods. A meta-analysis investigated whether or not trials published in journals
      that endorsed STRICTA were associated with better reporting. RESULTS: The study
      included 207 trials. Improved reporting of items over time was observed, as
      represented by changes in the scatterplot slope and intercept. The mean STRICTA
      score increased from 4.27 in the 1994-1995 period to 5.53 in 2014-2015, an 18%
      improvement. The mean CONSORT score rose from 1.01 in the 1994-1995 period to
      3.32 in 2014-2015, an increment of 46%. There was proportionately lower reporting
      for items related to practitioner background (STRICTA) and for randomisation
      implementation and allocation concealment (CONSORT). Trials published in journals
      that endorsed STRICTA had statistically significantly superior reporting of both
      STRICTA and CONSORT items overall. CONCLUSION: This study has provided evidence
      of an improvement in reporting of STRICTA and CONSORT items over the time period
      from 1994 to 2015. Journals that endorse STRICTA have a better record in terms of
      reporting quality. Some evidence suggests that the publication of STRICTA has had
      a positive impact on reporting quality.

PMID- 30201783
TI  - Multiple Flagellin Proteins Have Distinct and Synergistic Roles in Agrobacterium
      tumefaciens Motility.
AB  - Rotary flagella propel bacteria through liquid and across semisolid environments.
      Flagella are composed of the basal body that constitutes the motor for rotation,
      the curved hook that connects to the basal body, and the flagellar filament that
      propels the cell. Flagellar filaments can be composed of a single flagellin
      protein, such as in Escherichia coli, or made up of multiple flagellins, such as
      in Agrobacterium tumefaciens The four distinct flagellins FlaA, FlaB, FlaC, and
      FlaD produced by wild-type A. tumefaciens are not redundant in function but have
      specific properties. FlaA and FlaB are much more abundant than FlaC and FlaD and
      are readily observable in mature flagellar filaments, when either FlaA or FlaB is
      fluorescently labeled. Cells producing FlaA with any one of the other three
      flagellins can generate functional filaments and thus are motile, but FlaA alone
      cannot constitute a functional filament. In flaA mutants that manifest swimming
      deficiencies, there are multiple ways by which these mutations can be
      phenotypically suppressed. These suppressor mutations primarily occur within or
      upstream of the flaB flagellin gene or in the transcription factor sciP
      regulating flagellin expression. The helical conformation of the flagellar
      filament appears to require a key asparagine residue present in FlaA and absent
      in other flagellins. However, FlaB can be spontaneously mutated to render helical
      flagella in the absence of FlaA, reflecting their overall similarity and perhaps
      the subtle differences in the specific functions they have evolved to
      fulfill.IMPORTANCE Flagellins are abundant bacterial proteins comprising the
      flagellar filaments that propel bacterial movement. Several members of the
      alphaproteobacterial group express multiple flagellins, in contrast to model
      systems, such as with Escherichia coli, which has one type of flagellin. The
      plant pathogen Agrobacterium tumefaciens has four flagellins, the abundant and
      readily detected FlaA and FlaB, and lower levels of FlaC and FlaD. Mutational
      analysis reveals that FlaA requires at least one of the other flagellins to
      function, as flaA mutants produce nonhelical flagella and cannot swim
      efficiently. Suppressor mutations can rescue this swimming defect through
      mutations in the remaining flagellins, including structural changes imparting
      helical shape to the flagella, and putative regulators. Our findings shed light
      on how multiple flagellins contribute to motility.

PMID- 30201787
TI  - Immunotherapy for Prostate Cancer.
AB  - Immunotherapy with agents that block immune checkpoints is a mainstay of therapy
      for several common tumor types; so far, prostate cancer is not among those
      treated using this method. The observed lack of activity in prostate cancer is
      not due to a lack of testing; several agents have been evaluated both alone and
      in combination. Although several combination strategies show some promise, it
      appears likely that a greater understanding of the prostate cancer tumor
      microenvironment and baseline immune response will be required to optimize future
      treatment strategies.

PMID- 30201788
TI  - Vagus Nerve Stimulation at the Interface of Brain-Gut Interactions.
AB  - The vagus nerve, a key component of the cross-communication between the gut and
      the brain, is a major element of homeostasis sensing the "milieu interieur" and
      boosting the nervous and endocrine responses to maintain the gastrointestinal
      health status. This nerve has anti-inflammatory properties regulating the gut
      through the activation of the hypothalamic-pituitary-adrenal axis and the release
      of cortisol and through a vagovagal reflex, which has an anti-tumor necrosis
      factor (TNF) effect called the cholinergic anti-inflammatory pathway. Stimulating
      this nerve is an interesting tool as a nondrug therapy for the treatment of
      gastrointestinal diseases in which brain-gut communication is dysfunctional, such
      as inflammatory bowel disorders and others. This review presents the rationale of
      vagal gastrointestinal physiology and diseases and the most recent advances in
      vagus nerve stimulation. It also highlights the main issues to be addressed in
      the future to improve this bioelectronic therapy for gastrointestinal disorders.

PMID- 30201789
TI  - Sequencing in High Definition Drives a Changing Worldview of the Epigenome.
AB  - Single-molecule sequencing approaches have transformed the study of the human
      epigenome, accelerating efforts to describe genome function beyond the sequences
      that encode proteins. The post-genome era has ignited strong interest in the
      noncoding genome and profiling epigenetic signatures genome-wide have been
      critical for the identification and characterization of noncoding gene-regulatory
      sequences in various cellular and developmental contexts. These technologies
      enable quantification of epigenetic marks through digital assessment of DNA
      fragments. With the capacity to probe both the DNA sequence and count DNA
      molecules at once with unparalleled throughput and sensitivity, deep sequencing
      has been especially transformative to the study of DNA methylation. This review
      will discuss advances in epigenome profiling with a particular focus on DNA
      methylation, highlighting how deep sequencing has generated new insights into the
      role of DNA methylation in gene regulation. Technical aspects of profiling DNA
      methylation, remaining challenges, and the future of DNA methylation sequencing
      are also described.

PMID- 30201786
TI  - Macrophages of distinct origins contribute to tumor development in the lung.
AB  - Tissue-resident macrophages can self-maintain without contribution of adult
      hematopoiesis. Herein we show that tissue-resident interstitial macrophages (Res
      TAMs) in mouse lungs contribute to the pool of tumor-associated macrophages
      (TAMs) together with CCR2-dependent recruited macrophages (MoD-TAMs). Res-TAMs
      largely correlated with tumor cell growth in vivo, while MoD-TAMs accumulation
      was associated with enhanced tumor spreading. Both cell subsets were depleted
      after chemotherapy, but MoD-TAMs rapidly recovered and performed phagocytosis
      mediated tumor clearance. Interestingly, anti-VEGF treatment combined with
      chemotherapy inhibited both Res and Mod-TAM reconstitution without affecting
      monocyte infiltration and improved its efficacy. Our results reveal that the
      developmental origin of TAMs dictates their relative distribution, function, and
      response to cancer therapies in lung tumors.

PMID- 30201790
TI  - Efficacy of PD-1 or PD-L1 inhibitors and PD-L1 expression status in cancer: meta
      analysis.
AB  - OBJECTIVE: To evaluate the relative efficacy of programmed cell death 1 (PD-1) or
      programmed cell death ligand 1 (PD-L1) inhibitors versus conventional drugs in
      patients with cancer that were PD-L1 positive and PD-L1 negative. DESIGN: Meta
      analysis of randomised controlled trials. DATA SOURCES: PubMed, Embase, Cochrane
      database, and conference abstracts presented at the American Society of Clinical
      Oncology and European Society of Medical Oncology up to March 2018. REVIEW
      METHODS: Studies of PD-1 or PD-L1 inhibitors (avelumab, atezolizumab, durvalumab,
      nivolumab, and pembrolizumab) that had available hazard ratios for death based on
      PD-L1 positivity or negativity were included. The threshold for PD-L1 positivity
      or negativity was that PD-L1 stained cell accounted for 1% of tumour cells, or
      tumour and immune cells, assayed by immunohistochemistry staining methods.
      RESULTS: 4174 patients with advanced or metastatic cancers from eight randomised
      controlled trials were included in this study. Compared with conventional agents,
      PD-1 or PD-L1 inhibitors were associated with significantly prolonged overall
      survival in both patients that were PD-L1 positive (n=2254, hazard ratio 0.66,
      95% confidence interval 0.59 to 0.74) and PD-L1 negative (1920, 0.80, 0.71 to
      0.90). However, the efficacies of PD-1 or PD-L1 blockade treatment in patients
      that were PD-L1 positive and PD-L1 negative were significantly different (P=0.02
      for interaction). Additionally, in both patients that were PD-L1 positive and PD
      L1 negative, the long term clinical benefits from PD-1 or PD-L1 blockade were
      observed consistently across interventional agent, cancer histotype, method of
      randomisation stratification, type of immunohistochemical scoring system, drug
      target, type of control group, and median follow-up time. CONCLUSIONS: PD-1 or PD
      L1 blockade therapy is a preferable treatment option over conventional therapy
      for both patients that are PD-L1 positive and PD-L1 negative. This finding
      suggests that PD-L1 expression status alone is insufficient in determining which
      patients should be offered PD-1 or PD-L1 blockade therapy.

PMID- 30201791
TI  - Infographic. International Ankle Consortium Rehabilitation-Oriented Assessment.

PMID- 30201792
TI  - There are more football injury prevention reviews than randomised controlled
      trials. Time for more RCT action!

PMID- 30201793
TI  - Effectiveness of multicomponent lower extremity injury prevention programmes in
      team-sport athletes: an umbrella review.
AB  - OBJECTIVE: To identify which exercise combinations are most effective as part of
      a lower extremity injury prevention programme for team-sport athletes. DESIGN:
      Umbrella review. DATA SOURCES: A comprehensive literature search was performed in
      PubMed, Scopus, Cochrane Library and PEDro databases. Studies published between
      January 2000 and March 2017 were included in this umbrella review. STUDY
      ELIGIBILITY CRITERIA: Moderate to high-quality systematic reviews that
      investigated the effectiveness of a combination of two or more exercise
      components, that is, strength, agility, plyometrics, balance, stretching,
      technique, warm-up and functional activity, regarding injury incidence/rate of
      lower extremity injuries in team-sport athletes. The methodological quality of
      the included systematic reviews was independently assessed by two reviewers using
      the Assessing the Methodological Quality of Systematic Reviews measurement tool
      and the Grading of Recommendations Assessment, Development and Evaluation
      guidelines were used to assess the overall quality of evidence for particular
      outcomes. RESULTS: Twenty-four systematic reviews met the inclusion criteria.
      Multicomponent exercise interventions were effective in reducing the injury
      incidence/rate of lower extremity, knee, ACL and ankle injuries, but not groin
      injuries. Strength and balance exercise components were included in 10 of 11
      effective injury prevention programmes for the lower extremity, knee, ACL and
      ankle injuries. SUMMARY/CONCLUSION: Lower extremity injury prevention programmes
      in team sports are effective in preventing lower extremity, knee, ACL and ankle
      injuries. Lower extremity muscle strength and balance exercises should be
      prioritised in lower extremity injury prevention programmes for team-sport
      athletes.

PMID- 30201794
TI  - Modelling-based evaluation of the costs, benefits and cost-effectiveness of
      multipathogen point-of-care tests for sexually transmitted infections in
      symptomatic genitourinary medicine clinic attendees.
AB  - OBJECTIVES: To quantify the costs, benefits and cost-effectiveness of three
      multipathogen point-of-care (POC) testing strategies for detecting common
      sexually transmitted infections (STIs) compared with standard laboratory testing.
      DESIGN: Modelling study. SETTING: Genitourinary medicine (GUM) services in
      England. POPULATION: A hypothetical cohort of 965 988 people, representing the
      annual number attending GUM services symptomatic of lower genitourinary tract
      infection. INTERVENTIONS: The decision tree model considered costs and
      reimbursement to GUM services associated with diagnosing and managing STIs. Three
      strategies using hypothetical point-of-care tests (POCTs) were compared with
      standard care (SC) using laboratory-based testing. The strategies were: A) dual
      POCT for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG); B) triplex
      POCT for CT-NG and Mycoplasma genitalium (MG); C) quadruplex POCT for CT-NG-MG
      and Trichomonas vaginalis (TV). Data came from published literature and
      unpublished estimates. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcomes
      were total costs and benefits (quality-adjusted life years (QALYs)) for each
      strategy (2016 GB, L) and associated incremental cost-effectiveness ratios
      (ICERs) between each of the POC strategies and SC. Secondary outcomes were
      inappropriate treatment of STIs, onward STI transmission, pelvic inflammatory
      disease in women, time to cure and total attendances. RESULTS: In the base-case
      analysis, POC strategy C, a quadruplex POCT, was the most cost-effective relative
      to the other strategies, with an ICER of L36 585 per QALY gained compared with SC
      when using microcosting, and cost-savings of L26 451 382 when using tariff
      costing. POC strategy C also generated the most benefits, with 240 467 fewer
      clinic attendances, 808 fewer onward STI transmissions and 235 135 averted
      inappropriate treatments compared with SC. CONCLUSIONS: Many benefits can be
      achieved by using multipathogen POCTs to improve STI diagnosis and management.
      Further evidence is needed on the underlying prevalence of STIs and SC delivery
      in the UK to reduce uncertainty in economic analyses.

PMID- 30201796
TI  - Patients should not be denied access to hip surgery.

PMID- 30201795
TI  - Economic returns to medical research funding.
AB  - Following the publication of the final paper in a planned series of four studies
      estimating the economic returns from biomedical and health research, we reflect
      on what we have learnt from these types of assessment.

PMID- 30201798
TI  - Correction: Migration against the direction of flow is LFA-1-dependent in human
      hematopoietic stem and progenitor cells (doi: 10.1242/jcs.205575).

PMID- 30201797
TI  - Perioperative lung protective ventilation.
AB  - Perioperative lung injury is a major source of postoperative morbidity, excess
      healthcare use, and avoidable mortality. Many potential inciting factors can lead
      to this condition, including intraoperative ventilator induced lung injury.
      Questions exist as to whether protective ventilation strategies used in the
      intensive care unit for patients with acute respiratory distress syndrome are
      equally beneficial for surgical patients, most of whom do not present with any
      pre-existing lung pathology. Studied both individually and in combination as a
      package of intraoperative lung protective ventilation, the use of low tidal
      volumes, moderate positive end expiratory pressure, and recruitment maneuvers
      have been shown to improve oxygenation and pulmonary physiology and to reduce
      postoperative pulmonary complications in at risk patient groups. Further work is
      needed to define the potential contributions of alternative ventilator
      strategies, limiting excessive intraoperative oxygen supplementation, use of non
      invasive techniques in the postoperative period, and personalized mechanical
      ventilation. Although the weight of evidence strongly suggests a role for lung
      protective ventilation in moderate risk patient groups, definitive evidence of
      its benefit for the general surgical population does not exist. However, given
      the shift in understanding of what is needed for adequate oxygenation and
      ventilation under anesthesia, the largely historical arguments against the use of
      intraoperative lung protective ventilation may soon be outdated, on the basis of
      its expanding track record of safety and efficacy in multiple settings.

PMID- 30201799
TI  - Acetylation of SUMO2 at lysine 11 favors the formation of non-canonical SUMO
      chains.
AB  - Post-translational modifications by ubiquitin-related SUMO modifiers regulate
      cellular signaling networks and protein homeostasis. While SUMO1 is mainly
      conjugated to proteins as a monomer, SUMO2/3 can form polymeric chains. Poly
      SUMOylation is best understood in the SUMO-targeted ubiquitin ligase (StUbL)
      pathway, where chains prime proteins for subsequent ubiquitylation by StUbLs.
      SUMO chains typically form in response to genotoxic or proteotoxic stress and are
      preferentially linked via lysine 11 of SUMO2/3. Here, we report that K11 of
      SUMO2/3 undergoes reversible acetylation with SIRT1 being the K11 deacetylase. In
      a purified in vitro system, acetylation of SUMO2/3 impairs chain formation and
      restricts chain length. In a cellular context, however, K11 acetyl-mimicking
      SUMO2 does not affect the StUbL pathway, indicating that in cells non-canonical
      chains are more prevalent. MS-based SUMO proteomics indeed identified non
      canonical chain types under basal and stress conditions. Importantly, mimicking
      K11 acetylation alters chain architecture by favoring K5- and K35-linked chains,
      while inhibiting K7 and K21 linkages. These data provide insight into SUMO chain
      signaling and point to a role of K11 acetylation as a modulator of SUMO2/3
      chains.

PMID- 30201801
TI  - Biochemical Diagnosis of Pheochromocytoma, a Rediscovered Catecholamine
      Metabolizing Tumor.

PMID- 30201802
TI  - Updates on Screening, Prevention, Treatment, and Genetic Markers for
      Preeclampsia.

PMID- 30201800
TI  - Vesicle sub-pool organization at inner hair cell ribbon synapses.
AB  - The afferent inner hair cell synapse harbors the synaptic ribbon, which ensures a
      constant vesicle supply. Synaptic vesicles (SVs) are arranged in morphologically
      discernable pools, linked via filaments to the ribbon or the presynaptic
      membrane. We propose that filaments play a major role in SV resupply and
      exocytosis at the ribbon. Using advanced electron microscopy, we demonstrate that
      SVs are organized in sub-pools defined by the filament number per vesicle and its
      connections. Upon stimulation, SVs increasingly linked to other vesicles and to
      the ribbon, whereas single-tethered SVs dominated at the membrane. Mutant mice
      for the hair cell protein otoferlin (pachanga, Otof Pga/Pga ) are profoundly deaf
      with reduced sustained release, serving as a model to investigate the SV
      replenishment at IHCs. Upon stimulation, multiple-tethered and docked vesicles
      (rarely observed in wild-type) accumulated at Otof Pga/Pga active zones due to an
      impairment downstream of docking. Conclusively, vesicles are organized in sub
      pools at ribbon-type active zones by filaments to support vesicle supply,
      transport, and finally release.

PMID- 30201803
TI  - UPLC-MS/MS Analysis of Urinary Free Oligosaccharides for Lysosomal Storage
      Diseases: Diagnosis and Potential Treatment Monitoring.
AB  - BACKGROUND: The glycoproteinoses are a subgroup of lysosomal storage diseases
      (LSDs) resulting from impaired degradation of N-linked oligosaccharide side
      chains of glycoproteins, which are commonly screened by detecting the accumulated
      free oligosaccharides (FOSs) in urine via thin layer chromatography (TLC). The
      traditional TLC method suffers from limited analytical sensitivity and
      specificity and lacks quantification capability. Therefore, we developed an
      analytically sensitive and relatively specific assay using ultraperformance
      liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for urinary FOS
      analysis and validated its use for urine screening of glycoproteinoses and other
      LSDs. METHODS: Urine volumes equivalent to 30 MUg of creatinine were derivatized
      with butyl-4-aminobenzoate and then purified through a solid-phase extraction
      cartridge. A 7-min UPLC-MS/MS analysis was performed on a triple quadrupole mass
      spectrometer using an amide column for separation of derivatized FOS. Urine
      samples from >100 unaffected controls and 37 patients with various LSDs were
      studied. RESULTS: Relative quantification was conducted on 7 selected FOSs using
      a single internal standard, which allowed the identification of patients with 1
      of 8 different LSDs: aspartylglucosaminuria, alpha-fucosidosis, alpha
      mannosidosis, beta-mannosidosis, beta-galactosidase deficiency, Sandhoff disease,
      sialidosis, and galactosialidosis. Patients treated with hematopoietic stem cell
      transplant show decreased FOS responses compared with untreated patients.
      CONCLUSIONS: This UPLC-MS/MS assay offers a valuable tool for screening of
      glycoproteinoses and other LSDs, with potential use for future treatment
      monitoring.

PMID- 30201804
TI  - Adaptation to Endoplasmic Reticulum Stress Requires Trans-phosphorylation within
      the Activation Loop of Protein Kinases Kin1 and Kin2, Orthologs of Human
      Microtubule Affinity-regulating Kinase.
AB  - Perturbations in endoplasmic reticulum (ER) homeostasis, a condition termed the
      "ER stress", activate the unfolded protein response (UPR), an intracellular
      network of signaling pathways. Recently, we have shown that protein kinase Kin1
      and its paralog Kin2 in the budding yeast Saccharomyces cerevisiae (orthologs of
      microtubule affinity-regulating kinase in humans) contribute to the UPR function.
      These Kin kinases contain a conserved kinase domain and an auto-inhibitory kinase
      associated 1 (KA1) domain separated by a long undefined domain. Here, we show
      that Kin1 or Kin2 protein requires minimally a kinase domain and an adjacent
      kinase extension region (KER) for the UPR function. We also show that the
      functional mini Kin2 protein is predominantly visualized inside the cells and
      precipitated with the cellular membrane fraction, suggesting its association with
      the cellular endomembrane system. Furthermore, we show that trans-phosphorylation
      of the Kin1 residue T302 and the analogous Kin2 residue T281 within the
      activation loop are important for the full kinase activity. Collectively, our
      data suggest that, during the ER stress, the Kin kinase domain is released from
      its auto-inhibitory KA1 domain and is activated by trans-phosphorylation.

PMID- 30201805
TI  - The Cellular Senescence-Inhibited Gene Is Essential for PPM1A Myristoylation To
      Modulate Transforming Growth Factor beta Signaling.
AB  - The cellular senescence-inhibited gene (CSIG) is implicated in important
      biological processes, including cellular senescence and apoptosis. Our work
      showed that CSIG is involved in the myristoylation of the serine/threonine
      protein phosphatase PPM1A. Previous research has shown that myristoylation is
      necessary for PPM1A to dephosphorylate Smad2 and Smad3. However, the control and
      the biological significance of the myristoylation remain poorly understood. In
      this study, we found that CSIG knockdown disturbs PPM1A myristoylation and
      reduces the dephosphorylation by PPM1A of its substrate Smad2. By regulating
      PPM1A myristoylation, CSIG is involved in modulating the signaling of
      transforming growth factor beta (TGF-beta). Further study of the mechanism
      indicated that CSIG facilitates the interaction between N-myristoyltransferase 1
      (NMT1) and PPM1A. Taking the data together, we found that CSIG is a regulator of
      PPM1A myristoylation and TGF-beta signaling. By promoting the myristoylation of
      PPM1A, CSIG enhanced the phosphatase activity of PPM1A and further inhibited TGF
      beta signaling. This work not only extends the biological significance of CSIG
      but also provides new ideas and a reference for the study of the regulatory
      mechanism of myristoylation.

PMID- 30201807
TI  - Atypical porcine pestivirus in wild boar (Sus scrofa), Spain.

PMID- 30201806
TI  - RACK1 Specifically Regulates Translation through its Binding to Ribosomes.
AB  - The translational capability of ribosomes deprived of specific non-fundamental
      ribosomal proteins may be altered. Physiological mechanisms are scanty and it is
      unclear whether free ribosomal proteins can crosstalk with the signaling
      machinery. RACK1 (Receptor for Activated C Kinase 1) is a highly conserved
      scaffold protein, located on the 40S subunit near the mRNA exit channel. RACK1 is
      involved in a variety of intracellular contexts, both on and off the ribosomes,
      acting as a receptor for proteins in signaling like PKCs. Here we show that
      binding of RACK1 to ribosomes is essential for full translation of capped mRNAs
      and efficient recruitment of eIF4E (eukaryotic Initiation Factor 4E). In vitro,
      supplementing the ribosome machinery with wild-type RACK1 restores the
      translational capability, whereas addition of a RACK1 mutant unable to bind
      ribosomes does not. Out of the ribosome, RACK1 has a reduced half-life. By
      accumulating in living cells, free RACK1 exerts an inhibitory phenotype by
      impairing cell cycle progression and repressing global translation. Here we
      present RACK1 binding to ribosomes as a crucial way to regulate translation,
      possibly by interacting with known signaling-involved partners on or out of the
      ribosome.

PMID- 30201808
TI  - Phenotypic and Functional Signatures of Herpes Simplex Virus-Specific Effector
      Memory CD73+CD45RAhighCCR7lowCD8+ TEMRA and CD73+CD45RAlowCCR7lowCD8+ TEM Cells
      Are Associated with Asymptomatic Ocular Herpes.
AB  - HSV type 1 (HSV-1)-specific CD8+ T cells protect from herpes infection and
      disease. However, the nature of protective CD8+ T cells in HSV-1 seropositive
      healthy asymptomatic (ASYMP) individuals (with no history of clinical herpes
      disease) remains to be determined. In this study, we compared the phenotype and
      function of HSV-specific CD8+ T cells from HLA-A*02:01-positive ASYMP and
      symptomatic (SYMP) individuals (with a documented history of numerous episodes of
      recurrent ocular herpetic disease). We report that although SYMP and ASYMP
      individuals have similar frequencies of HSV-specific CD8+ T cells, the
      "naturally" protected ASYMP individuals have a significantly higher proportion of
      multifunctional HSV-specific effector memory CD8+ T cells
      (CD73+CD45RAhighCCR7lowCD8+ effector memory RA (TEMRA) and
      CD73+CD45RAlowCCR7lowCD8+ effector memory (TEM) as compared with SYMP
      individuals. Similar to humans, HSV-1-infected ASYMP B6 mice had frequent
      multifunctional HSV-specific CD73+CD8+ T cells in the cornea, as compared with
      SYMP mice. Moreover, in contrast to wild type B6, CD73-/- deficient mice infected
      ocularly with HSV-1 developed more recurrent corneal herpetic infection and
      disease. This was associated with less functional CD8+ T cells in the cornea and
      trigeminal ganglia, the sites of acute and latent infection. The phenotypic and
      functional characteristics of HSV-specific circulating and in situ CD73+CD8+ T
      cells, demonstrated in both ASYMP humans and mice, suggest a positive role for
      effector memory CD8+ T cells expressing the CD73 costimulatory molecule in the
      protection against ocular herpes infection and disease. These findings are
      important for the development of safe and effective T cell-based herpes
      immunotherapy.

PMID- 30201809
TI  - Cutting Edge: Intracellular IFN-beta and Distinct Type I IFN Expression Patterns
      in Circulating Systemic Lupus Erythematosus B Cells.
AB  - In systemic lupus erythematosus (SLE), type I IFNs promote induction of type I
      IFN-stimulated genes (ISG) and can drive B cells to produce autoantibodies.
      Little is known about the expression of distinct type I IFNs in lupus,
      particularly high-affinity IFN-beta. Single-cell analyses of transitional B cells
      isolated from SLE patients revealed distinct B cell subpopulations, including
      type I IFN producers, IFN responders, and mixed IFN producer/responder clusters.
      Anti-Ig plus TLR3 stimulation of SLE B cells induced release of bioactive type I
      IFNs that could stimulate HEK-Blue cells. Increased levels of IFN-beta were
      detected in circulating B cells from SLE patients compared with controls and were
      significantly higher in African American patients with renal disease and in
      patients with autoantibodies. Together, the results identify type I IFN-producing
      and -responding subpopulations within the SLE B cell compartment and suggest that
      some patients may benefit from specific targeting of IFN-beta.

PMID- 30201811
TI  - beta1 Integrins Are Required To Mediate NK Cell Killing of Cryptococcus
      neoformans.
AB  - Cryptococcus neoformans is a fungal pathogen that causes fatal meningitis and
      pneumonia. During host defense to Cryptococcus, NK cells directly recognize and
      kill C. neoformans using cytolytic degranulation analogous to killing of tumor
      cells. This fungal killing requires independent activation of Src family kinase
      (SFK) and Rac1-mediated pathways. Recognition of C. neoformans requires the
      natural cytotoxicity receptor, NKp30; however, it is not known whether NKp30
      activates both signal transduction pathways or whether a second receptor is
      involved in activation of one of the pathways. We used primary human NK cells and
      a human NK cell line and found that NKp30 activates SFK -> PI3K but not Rac1
      cytotoxic signaling, which led to a search for the receptor leading to Rac1
      activation. We found that NK cells require integrin-linked kinase (ILK) to
      activate Rac1 for effective fungal killing. This observation led to our
      identification of beta1 integrin as an essential anticryptococcal receptor. These
      findings demonstrate that multiple receptors, including beta1 integrins and NKp30
      and their proximal signaling pathways, are required for recognition of
      Cryptococcus, which activates a central cytolytic antimicrobial pathway leading
      to fungal killing.

PMID- 30201812
TI  - Presenilin 1 Regulates NF-kappaB Activation via Association with Breakpoint
      Cluster Region and Casein Kinase II.
AB  - We recently reported that NF-kappaB-mediated inflammation caused by breakpoint
      cluster region (BCR) is dependent on the alpha subunit of casein kinase II
      (CK2alpha) complex. In the current study, we demonstrate that presenilin 1
      (Psen1), which is a catalytic component of the gamma-secretase complex and the
      mutations of which are known to cause familial Alzheimer disease, acts as a
      scaffold of the BCR-CK2alpha-p65 complex to induce NF-kappaB activation. Indeed,
      Psen1 deficiency in mouse endothelial cells showed a significant reduction of NF
      kappaB p65 recruitment to target gene promoters. Conversely, Psen1 overexpression
      enhanced reporter activation under NF-kappaB responsive elements and IL-6
      promoter. Furthermore, the transcription of NF-kappaB target genes was not
      inhibited by a gamma-secretase inhibitor, suggesting that Psen1 regulates NF
      kappaB activation in a manner independent of gamma-secretase activity.
      Mechanistically, Psen1 associated with the BCR-CK2alpha complex, which is
      required for phosphorylation of p65 at serine 529. Consistently, TNF-alpha
      induced phosphorylation of p65 at serine 529 was significantly decreased in Psen1
      deficient cells. The association of the BCR-CK2alpha-p65 complex was perturbed in
      the absence of Psen1. These results suggest that Psen1 functions as a scaffold of
      the BCR-CK2alpha-p65 complex and that this signaling cascade could be a novel
      therapeutic target for various chronic inflammation conditions, including those
      in Alzheimer disease.

PMID- 30201810
TI  - Oxidant Signaling Mediated by Nox2 in Neutrophils Promotes Regenerative
      Myelopoiesis and Tissue Recovery following Ischemic Damage.
AB  - Ischemic tissue damage activates hematopoietic stem and progenitor cells (HSPCs)
      in the bone marrow (BM)-generating myeloid cells, and persistent HSPC activity
      may drive chronic inflammation and impair tissue recovery. Although increased
      reactive oxygen species in the BM regulate HSPC functions, their roles in
      myelopoiesis of activated HSPCs and subsequent tissue recovery during ischemic
      damage are not well understood. In this paper, we report that deletion of Nox2
      NADPH oxidase in mice results in persistent elevations in BM HSPC activity and
      levels of inflammatory monocytes/macrophages in BM and ischemic tissue in a model
      of hindlimb ischemia. Ischemic tissue damage induces oxidants in BM such as
      elevations of hydrogen peroxide and oxidized phospholipids, which activate redox
      sensitive Lyn kinase in a Nox2-dependent manner. Moreover, during tissue recovery
      after ischemic injury, this Nox2-ROS-Lyn kinase axis is induced by Nox2 in
      neutrophils that home to the BM, which inhibits HSPC activity and inflammatory
      monocyte generation and promotes tissue regeneration after ischemic damage. Thus,
      oxidant signaling in the BM mediated by Nox2 in neutrophils regulates
      myelopoiesis of HSPCs to promote regeneration of damaged tissue.

PMID- 30201813
TI  - Antiplatelet therapy and the risk of ischemic and hemorrhagic complications
      associated with Pipeline embolization of cerebral aneurysms: a systematic review
      and pooled analysis.
AB  - BACKGROUND: Pipeline embolization devices (PEDs) are increasingly used in the
      treatment of cerebral aneurysms. Yet, major ischemic or hemorrhagic complications
      after PED treatment associated with antiplatelet regimens are not well
      established. OBJECTIVE: To investigate the risk of ischemic and hemorrhagic
      complications associated with common antiplatelet regimens following PED
      treatment, and to examine whether platelet function testing (PFT) is associated
      with a lower risk of these complications. METHODS: We searched Medline, Embase,
      and Cochrane from 2009 to 2017. Twenty-nine studies were included that had
      reported a uniform antiplatelet regimen protocol and had provided data on major
      ischemic and hemorrhagic complications following PED treatment. Random-effect
      meta-analysis was used to pool overall ischemic and hemorrhagic event rates
      across studies. The rate of these complications with respect to the
      antithrombotic regimen and PFT was assessed by chi2 proportional tests. RESULTS:
      Overall, 2002 patients (age 55.9 years, 76% female) were included. A low-dose
      acetylsalicylic acid (ASA) regimen before and after PED treatment was associated
      with a higher rate of late ischemic complications than with high-dose ASA therapy
      (2.62 (95% CI 1.46 to 4.69) and 2.56 (1.41 to 4.64), respectively). Duration of
      post-procedure clopidogrel therapy <6 months was associated with greater rates of
      ischemic complications (1.56, 95% CI 1.11 to 2.20) than a clopidogrel regimen of
      >=6 months. Performing PFT before PED treatment was not associated with the risk
      of ischemic complications (1.27, 95% CI 0.77 to 2.10). CONCLUSION: High-dose ASA
      therapy and clopidogrel treatment for at least 6 months were associated with a
      reduced incidence of ischemic events, without affecting the risk of hemorrhagic
      events.

PMID- 30201814
TI  - Isavuconazole for Treatment of Experimental Fungal Endophthalmitis Caused by
      Aspergillus fumigatus.
AB  - Fungal endophthalmitis remains a significant cause of vision impairment and
      blindness. Moreover, the prognosis is poor, in part due to delay in diagnosis and
      to limited availability of effective antifungal agents with good ocular
      penetration. Thus, it is imperative to evaluate the therapeutic efficacy in
      fungal endophthalmitis of newer antifungal agents. In this study, we assessed the
      efficacy of isavuconazole in treating Aspergillus fumigatus endophthalmitis in an
      exogenous mouse model of the disease. Briefly, endophthalmitis was induced by
      intravitreal (IVT) injection of A. fumigatus spores into immunocompetent C57BL/6
      (B6) mouse eyes. Mice were randomized into five groups that received
      isavuconazole via (i) oral gavage, (ii) IVT injections, (iii) intravenous
      injection, (iv) IVT injection followed by oral gavage, and (v) IVT injection
      followed by intravenous injection. Our data showed that isavuconazole treatment
      via all routes reduced fungal burden in A. fumigatus-infected eyes. This
      coincided with the preservation of retinal structural integrity (histology
      analysis) and retinal function (electroretinography [ERG] analysis), resulting in
      significantly improved disease outcome. Furthermore, isavuconazole treatment
      reduced the levels of inflammatory cytokines (tumor necrosis factor alpha [TNF
      alpha], interleukin 1beta [IL-1beta], and IL-6) and cellular infiltration in the
      eyes. Notably, oral administration of isavuconazole was as effective in
      ameliorating endophthalmitis as intravitreal injection of the drug. Collectively,
      our study demonstrates that isavuconazole is effective in treating A. fumigatus
      endophthalmitis in mice, indicating its potential use in human ocular infections.

PMID- 30201816
TI  - Chloroquine Analogues as Leads against Pneumocystis Lung Pathogens.
AB  - The impact of Pneumocystis pneumonia (PcP) on morbidity and mortality remains
      substantial for immunocompromised individuals, including those afflicted by HIV
      infection, organ transplantation, cancer, autoimmune diseases, or subject to
      chemotherapy or corticosteroid-based therapies. Previous work from our group has
      shown that repurposing antimalarial compounds for PcP holds promise for treatment
      of this opportunistic infection. Following our previous discovery of chloroquine
      analogues with dual-stage antimalarial action both in vitro and in vivo, we now
      report the potent action of these compounds on Pneumocystis carinii in vitro
      Identification of chloroquine analogues as anti-PcP leads is an unprecedented
      finding.

PMID- 30201815
TI  - Identification of FDA-Approved Drugs as Antivirulence Agents Targeting the pqs
      Quorum-Sensing System of Pseudomonas aeruginosa.
AB  - The long-term use of antibiotics has led to the emergence of multidrug-resistant
      bacteria. A promising strategy to combat bacterial infections aims at hampering
      their adaptability to the host environment without affecting growth. In this
      context, the intercellular communication system quorum sensing (QS), which
      controls virulence factor production and biofilm formation in diverse human
      pathogens, is considered an ideal target. Here, we describe the identification of
      new inhibitors of the pqs QS system of the human pathogen Pseudomonas aeruginosa
      by screening a library of 1,600 U.S. Food and Drug Administration-approved drugs.
      Phenotypic characterization of ad hoc engineered strains and in silico molecular
      docking demonstrated that the antifungal drugs clotrimazole and miconazole, as
      well as an antibacterial compound active against Gram-positive pathogens,
      clofoctol, inhibit the pqs system, probably by targeting the transcriptional
      regulator PqsR. The most active inhibitor, clofoctol, specifically inhibited the
      expression of pqs-controlled virulence traits in P. aeruginosa, such as pyocyanin
      production, swarming motility, biofilm formation, and expression of genes
      involved in siderophore production. Moreover, clofoctol protected Galleria
      mellonella larvae from P. aeruginosa infection and inhibited the pqs QS system in
      P. aeruginosa isolates from cystic fibrosis patients. Notably, clofoctol is
      already approved for clinical treatment of pulmonary infections caused by Gram
      positive bacterial pathogens; hence, this drug has considerable clinical
      potential as an antivirulence agent for the treatment of P. aeruginosa lung
      infections.

PMID- 30201817
TI  - Characterization of Influenza B Virus Variants with Reduced Neuraminidase
      Inhibitor Susceptibility.
AB  - Treatment options for influenza B virus infections are limited to neuraminidase
      inhibitors (NAIs), which block the neuraminidase (NA) glycoprotein on the virion
      surface. The development of NAI resistance would therefore result in a loss of
      antiviral treatment options for influenza B virus infections. This study
      characterized two contemporary influenza B viruses with known resistance
      conferring NA amino acid substitutions, D197N and H273Y, detected during routine
      surveillance. The D197N and H273Y variants were characterized in vitro by
      assessing NA enzyme activity and affinity, as well as replication in cell culture
      compared to those of NAI-sensitive wild-type viruses. In vivo studies were also
      performed in ferrets to assess the replication and transmissibility of each
      variant. Mathematical models were used to analyze within-host and between-host
      fitness of variants relative to wild-type viruses. The data revealed that the
      H273Y variant had NA enzyme function similar to that of its wild type but had
      slightly reduced replication and transmission efficiency in vivo The D197N
      variant had impaired NA enzyme function, but there was no evidence of reduction
      in replication or transmission efficiency in ferrets. Our data suggest that the
      influenza B virus variant with the H273Y NA substitution had a more notable
      reduction in fitness compared to wild-type viruses than the influenza B variant
      with the D197N NA substitution. Although a D197N variant is yet to become
      widespread, it is the most commonly detected NAI-resistant influenza B virus in
      surveillance studies. Our results highlight the need to carefully monitor
      circulating viruses for the spread of influenza B viruses with the D197N NA
      substitution.

PMID- 30201818
TI  - Novel Self-Assembled Micelles Based on Cholesterol-Modified Antimicrobial Peptide
      (DP7) for Safe and Effective Systemic Administration in Animal Models of
      Bacterial Infection.
AB  - Owing to their broad-spectrum antibacterial properties, multitarget effects, and
      low drug resistance, antimicrobial peptides (AMPs) have played critical roles in
      the clinical therapy of drug-resistant bacterial infections. However, the
      potential hazard of hemolysis following systemic administration has greatly
      limited their application. Here, we developed a novel AMP derivative, DP7-C, by
      modifying a formerly identified highly active AMP (DP7) with cholesterol to form
      an amphiphilic conjugate. The prepared DP7-C easily self-assembled into stable
      nanomicelles in aqueous solution. The DP7-C micelles showed lower hemolytic
      activity than their unconjugated counterparts toward human red blood cells and a
      maximum tolerated dose of 80 mg/kg of body weight in mice via intravenous
      injection, thus demonstrating improved safety. Moreover, by eliciting specific
      immunomodulatory activities in immune cells, the DP7-C micelles exerted distinct
      therapeutic effects in zebrafish and mouse models of infection. In conclusion,
      DP7-C micelles may be an excellent candidate for the treatment of bacterial
      infections in the clinic.

PMID- 30201820
TI  - Population Pharmacokinetics of Tafenoquine, a Novel Antimalarial.
AB  - Tafenoquine is a novel 8-aminoquinoline antimalarial drug recently approved by
      the U.S. Food and Drug Administration (FDA) for the radical cure of acute
      Plasmodium vivax malaria, which is the first new treatment in almost 60 years. A
      population pharmacokinetic (POP PK) analysis was conducted with tafenoquine
      exposure data obtained following oral administration from 6 clinical studies in
      phase 1 through phase 3 with a nonlinear mixed effects modeling approach. The
      impacts of patient demographics, baseline characteristics, and extrinsic factors,
      such as formulation, were evaluated. Model performance was assessed using
      techniques such as bootstrapping, visual predictive checks, and external data
      validation from a phase 3 study not used in model fitting and parameter
      estimation. Based on the analysis, the systemic pharmacokinetics of tafenoquine
      were adequately described using a two-compartment model. The final POP PK model
      included body weight (allometric scaling) on apparent oral and intercompartmental
      clearance (CL/F and Q/F, respectively), apparent volume of distribution for
      central and peripheral compartments (V 2/F and V 3/F, respectively), formulation
      on systemic bioavailability (F1) and absorption rate constant (Ka ), and health
      status on apparent volume of distribution. The key tafenoquine population
      parameter estimates were 2.96 liters/h for CL/F and 915 liters for V 2/F in P.
      vivax-infected subjects. Additionally, the analyses demonstrated no clinically
      relevant difference in relative bioavailability across the capsule and tablet
      formulations administered in these clinical studies. In conclusion, a POP PK
      model for tafenoquine was developed. Clinical trial simulations based on this
      model supported bridging the exposures across two different formulations. This
      POP PK model can be applied to aid and perform clinical trial simulations in
      other scenarios and populations, such as pediatric populations.

PMID- 30201819
TI  - Expression of Pseudomonas aeruginosa Antibiotic Resistance Genes Varies Greatly
      during Infections in Cystic Fibrosis Patients.
AB  - The lungs of individuals with cystic fibrosis (CF) become chronically infected
      with Pseudomonas aeruginosa that is difficult to eradicate by antibiotic
      treatment. Two key P. aeruginosa antibiotic resistance mechanisms are the AmpC
      beta-lactamase that degrades beta-lactam antibiotics and MexXYOprM, a three
      protein efflux pump that expels aminoglycoside antibiotics from the bacterial
      cells. Levels of antibiotic resistance gene expression are likely to be a key
      factor in antibiotic resistance but have not been determined during infection.
      The aims of this research were to investigate the expression of the ampC and mexX
      genes during infection in patients with CF and in bacteria isolated from the same
      patients and grown under laboratory conditions. P. aeruginosa isolates from 36 CF
      patients were grown in laboratory culture and gene expression measured by reverse
      transcription-quantitative PCR (RT-qPCR). The expression of ampC varied over
      20,000-fold and that of mexX over 2,000-fold between isolates. The median
      expression levels of both genes were increased by the presence of subinhibitory
      concentrations of antibiotics. To measure P. aeruginosa gene expression during
      infection, we carried out RT-qPCR using RNA extracted from fresh sputum samples
      obtained from 31 patients. The expression of ampC varied over 4,000-fold, while
      mexX expression varied over 100-fold, between patients. Despite these wide
      variations, median levels of expression of ampC in bacteria in sputum were
      similar to those in laboratory-grown bacteria. The expression of mexX was higher
      in sputum than in laboratory-grown bacteria. Overall, our data demonstrate that
      genes that contribute to antibiotic resistance can be highly expressed in
      patients, but there is extensive isolate-to-isolate and patient-to-patient
      variation.

PMID- 30201821
TI  - Growth hormone treatment of Canadian children: results from the GeNeSIS phase IV
      prospective observational study.
AB  - BACKGROUND: Country-specific data on outcomes of treatment with recombinant human
      growth hormone are lacking. We present such data for children treated with growth
      hormone in Canada. METHODS: We describe characteristics and outcomes of 850
      children (mean age at baseline 8.5 yr) treated with growth hormone constituting
      the Canadian cohort of the multinational phase IV prospective observational
      Genetics and Neuroendocrinology of Short-stature International Study (GeNeSIS).
      The diagnosis associated with short stature was as determined by the
      investigator. Auxological data were evaluated yearly until near-adult height.
      Adverse events were assessed in all growth-hormone-treated patients. RESULTS: The
      diagnosis ascribed as the cause of short stature was growth hormone deficiency in
      526 children (61.9%), predominantly organic rather than idiopathic, particularly
      congenital pituitary abnormalities and intracranial tumours. All diagnostic
      groups with sufficient patients for analysis had increased height velocity
      standard deviation score (SDS) and height SDS during growth hormone treatment.
      For patients who reached near-adult height (n = 293), the mean height SDS was
      within the normal range for about 80% of patients with organic growth hormone
      deficiency (n = 131) or idiopathic growth hormone deficiency (n = 50), 50% of
      patients with idiopathic short stature (n = 10) and 46% of patients with Turner
      syndrome (n = 79). Eleven deaths were reported, 7 in patients with organic growth
      hormone deficiency. Serious adverse events considered related to growth hormone
      treatment (n = 19) were isolated except for medulloblastoma recurrence (n = 2)
      and adenoidal hypertrophy (n = 2). INTERPRETATION: Growth hormone treatment was
      effective and had a good safety profile in Canadian children. Growth hormone
      dosages were lower than in the US and global GeNeSIS cohorts, and a greater
      proportion of treated Canadian children had organic growth hormone deficiency.
      STUDY REGISTRATION: ClinicalTrials.gov, no. NCT01088412.

PMID- 30201824
TI  - Nectary Specification in Petunia and Arabidopsis.

PMID- 30201822
TI  - CIK Receptor Kinases Determine Cell Fate Specification during Early Anther
      Development in Arabidopsis.
AB  - Appropriate cell division and differentiation ensure normal anther development in
      angiosperms. BARELY ANY MERISTEM 1/2 (BAM1/2) and RECEPTOR-LIKE PROTEIN KINASE2
      (RPK2), two groups of leucine-rich repeat receptor-like protein kinases, are
      required for early anther cell specification. However, little is known about the
      molecular mechanisms underlying these two RLK-mediated signaling pathways. Here,
      we show that CLAVATA3 INSENSITIVE RECEPTOR KINASEs (CIKs), a group of novel
      coreceptor protein kinase-controlling stem cell homeostasis, play essential roles
      in BAM1/2- and RPK2-regulated early anther development in Arabidopsis thaliana
      The archesporial cells of cik1/2/3 triple and cik1/2/3/4 quadruple mutant anthers
      perform anticlinal division instead of periclinal division. Defective cell
      division and specification of the primary and inner secondary parietal cells
      occur in these mutant anthers. The disordered divisions and specifications of
      anther wall cells finally result in excess microsporocytes and a lack of one to
      three parietal cell layers in mutant anthers, resembling rpk2 or bam1/2 mutant
      anthers. Genetic and biochemical analyses indicate that CIKs function as
      coreceptors of BAM1/2 and RPK2 to regulate archesporial cell division and
      determine the specification of anther parietal cells.

PMID- 30201825
TI  - Hyperactivation of MAPK Signaling Is Deleterious to RAS/RAF-mutant Melanoma.
AB  - The most frequent genetic alterations in melanoma are gain-of-function (GOF)
      mutations in BRAF, which result in RAF-MEK-ERK signaling pathway addiction.
      Despite therapeutic success of RAF and MEK inhibitors in treating BRAFV600-mutant
      tumors, a major challenge is the inevitable emergence of drug resistance, which
      often involves reactivation of the MAPK pathway. Interestingly, resistant tumors
      are often sensitive to drug withdrawal, suggesting that hyperactivation of the
      MAPK pathway is not tolerated. To further characterize this phenomenon, isogenic
      models of inducible MAPK hyperactivation in BRAFV600E melanoma cells were
      generated by overexpression of ERK2. Using this model system, supraphysiologic
      levels of MAPK signaling led to cell death, which was reversed by MAPK
      inhibition. Furthermore, complete tumor regression was observed in an ERK2
      overexpressing xenograft model. To identify mediators of MAPK hyperactivation
      induced cell death, a large-scale pooled shRNA screen was conducted, which
      revealed that only shRNAs against BRAF and MAP2K1 rescued loss of cell viability.
      This suggested that no single downstream ERK2 effector was required, consistent
      with pleiotropic effects on multiple cellular stress pathways. Intriguingly, the
      detrimental effect of MAPK hyperactivation could be partially attributed to
      secreted factors, and more than 100 differentially secreted proteins were
      identified. The effect of ERK2 overexpression was highly context dependent, as
      RAS/RAF mutant but not RAS/RAF wild-type melanoma were sensitive to this
      perturbation.Implications: This vulnerability to MAPK hyperactivation raises the
      possibility of novel therapeutic approaches for RAS/RAF-mutant cancers. Mol
      Cancer Res; 1-13. (c)2018 AACR.

PMID- 30201826
TI  - Repurposing of mTOR Complex Inhibitors Attenuates MCL-1 and Sensitizes to PARP
      Inhibition.
AB  - MCL-1, a member of the antiapoptotic BCL-2 family, is a prosurvival protein with
      an essential DNA repair function. This study aims to test whether inhibition of
      protein synthesis by mTOR complex (mTORC) inhibitors depletes MCL-1, suppresses
      homologous recombination (HR) repair, and sensitizes cancer cells to PARP
      inhibitors. Treatment with everolimus decreases MCL-1 in colorectal carcinomas
      and small cell lung cancer (SCLC) cells but not glioblastoma multiforme (GBM)
      cells with a PTEN mutational background. However, AZD2014, a dual mTORC
      inhibitor, depletes MCL-1 in GBMs. Further, we show that everolimus decreases
      4EBP1 phosphorylation only in colorectal carcinoma, whereas AZD2014 decreases
      4EBP1 phosphorylation in both colorectal carcinoma and GBM cells. Combination
      therapy using everolimus or AZD2014 with olaparib inhibits the growth of clone A
      and U87-MG xenografts in in vivo and decreases clonogenic survival in in vitro
      compared with monotherapy. Reintroduction of MCL-1 rescues the survival of cancer
      cells in response to combination of everolimus or AZD2014 with olaparib.
      Treatment of cells with mTORC inhibitors and olaparib increases gamma-H2AX and
      53BP1 foci, decreases BRCA1, RPA, and Rad51 foci, impairs phosphorylation of
      ATR/Chk1 kinases, and induces necroptosis. In summary, mTORC inhibitors deplete
      MCL-1 to suppress HR repair and increase sensitivity to olaparib both in in vitro
      and in xenografts.Implications: Targeting the DNA repair activity of MCL-1 in in
      vivo for cancer therapy has not been tested. This study demonstrates that
      depleting MCL-1 sensitizes cancer cells to PARP inhibitors besides eliciting
      necroptosis, which could stimulate antitumor immunity to improve the therapeutic
      intervention of cancers. Mol Cancer Res; 1-12. (c)2018 AACR.

PMID- 30201823
TI  - Maize Oxalyl-CoA Decarboxylase1 Degrades Oxalate and Affects the Seed Metabolome
      and Nutritional Quality.
AB  - The organic acid oxalate occurs in microbes, animals, and plants; however,
      excessive oxalate accumulation in vivo is toxic to cell growth and decreases the
      nutritional quality of certain vegetables. However, the enzymes and functions
      required for oxalate degradation in plants remain largely unknown. Here, we
      report the cloning of a maize (Zea mays) opaque endosperm mutant that encodes
      oxalyl-CoA decarboxylase1 (EC4.1.1.8; OCD1). Ocd1 is generally expressed and is
      specifically induced by oxalate. The ocd1 mutant seeds contain a significantly
      higher level of oxalate than the wild type, indicating that the ocd1 mutants have
      a defect in oxalate catabolism. The maize classic mutant opaque7 (o7) was
      initially cloned for its high lysine trait, although the gene function was not
      understood until its homolog in Arabidopsis thaliana was found to encode an
      oxalyl-CoA synthetase (EC 6.2.1.8), which ligates oxalate and CoA to form oxalyl
      CoA. Our enzymatic analysis showed that ZmOCD1 catalyzes oxalyl-CoA, the product
      of O7, into formyl-CoA and CO2 for degradation. Mutations in ocd1 caused dramatic
      alterations in the metabolome in the endosperm. Our findings demonstrate that
      ZmOCD1 acts downstream of O7 in oxalate degradation and affects endosperm
      development, the metabolome, and nutritional quality in maize seeds.

PMID- 30201827
TI  - Impact of antibiotics for children presenting to general practice with cough on
      adverse outcomes: secondary analysis from a multicentre prospective cohort study.
AB  - BACKGROUND: Clinicians commonly prescribe antibiotics to prevent major adverse
      outcomes in children presenting in primary care with cough and respiratory
      symptoms, despite limited meaningful evidence of impact on these outcomes. AIM:
      To estimate the effect of children's antibiotic prescribing on adverse outcomes
      within 30 days of initial consultation. DESIGN AND SETTING: Secondary analysis of
      8320 children in a multicentre prospective cohort study, aged 3 months to <16
      years, presenting in primary care across England with acute cough and other
      respiratory symptoms. METHOD: Baseline clinical characteristics and antibiotic
      prescribing data were collected, and generalised linear models were used to
      estimate the effect of antibiotic prescribing on adverse outcomes within 30 days
      (subsequent hospitalisations and reconsultation for deterioration), controlling
      for clustering and clinicians' propensity to prescribe antibiotics. RESULTS:
      Sixty-five (0.8%) children were hospitalised and 350 (4%) reconsulted for
      deterioration. Clinicians prescribed immediate and delayed antibiotics to 2313
      (28%) and 771 (9%), respectively. Compared with no antibiotics, there was no
      clear evidence that antibiotics reduced hospitalisations (immediate antibiotic
      risk ratio [RR] 0.83, 95% confidence interval [CI] = 0.47 to 1.45; delayed RR
      0.70, 95% CI = 0.26 to 1.90, overall P = 0.44). There was evidence that delayed
      (rather than immediate) antibiotics reduced reconsultations for deterioration
      (immediate RR 0.82, 95% CI = 0.65 to 1.07; delayed RR 0.55, 95% CI = 0.34 to
      0.88, overall P = 0.024). CONCLUSION: Most children presenting with acute cough
      and respiratory symptoms in primary care are not at risk of hospitalisation, and
      antibiotics may not reduce the risk. If an antibiotic is considered, a delayed
      antibiotic prescription may be preferable as it is likely to reduce
      reconsultation for deterioration.

PMID- 30201830
TI  - Phenomenology as a healthcare research method.

PMID- 30201828
TI  - Treatments for subacute cough in primary care: systematic review and meta
      analyses of randomised clinical trials.
AB  - BACKGROUND: Subacute cough following a non-specific viral infection lasting 3-8
      weeks is common. However, despite many treatment options there are no systematic
      reviews evaluating these. AIM: To provide a systematic overview of treatment
      options and outcomes evaluated in randomised clinical trials (RCTs). DESIGN AND
      SETTING: Systematic review and meta-analyses assessing the overall effects of any
      treatment for subacute cough. METHOD: The authors systematically searched
      PubMed/MEDLINE and the Cochrane Central Register of Controlled Trials (last
      search March 2017) for RCTs in adult patients with subacute cough. The authors
      considered trials evaluating any outcome of any drug or non-drug treatments,
      apart from traditional Chinese and Asian medicines. They combined treatment
      effects on cough-related outcomes in random effects meta-analyses. RESULTS: Six
      eligible RCTs including 724 patients were identified. These assessed montelukast,
      salbutamol plus ipratropium bromide, gelatine, fluticasone propionate,
      budesonide, and nociception opioid 1 receptor agonist and codeine. Five studies
      reported effects on various cough severity scores at various timepoints. No
      treatment option was associated with a clear benefit on cough recovery or other
      patient-relevant outcomes in any of the studies or in meta-analyses for cough
      outcomes at 14 days and 28 days. Reported adverse events were rather mild and
      reported for 14% of patients across all treatments. CONCLUSION: Evidence on
      treatment options for subacute cough is weak. There is no treatment showing clear
      patient-relevant benefits in clinical trials.

PMID- 30201829
TI  - Poisoning substances taken by young people: a population-based cohort study.
AB  - BACKGROUND: Globally, poisonings account for most medically-attended self-harm.
      Recent data on poisoning substances are lacking, but are needed to inform self
      harm prevention. AIM: To assess poisoning substance patterns and trends among 10
      24-year-olds across England DESIGN AND SETTING: Open cohort study of 1 736 527
      young people, using linked Clinical Practice Research Datalink, Hospital Episode
      Statistics, and Office for National Statistics mortality data, from 1998 to 2014.
      METHOD: Poisoning substances were identified by ICD-10 or Read Codes. Incidence
      rates and adjusted incidence rate ratios (aIRR) were calculated for poisoning
      substances by age, sex, index of multiple deprivation, and calendar year.
      RESULTS: In total, 40 333 poisoning episodes were identified, with 57.8%
      specifying the substances involved. The most common substances were paracetamol
      (39.8%), alcohol (32.7%), non-steroidal anti-inflammatory drugs (NSAIDs) (11.6%),
      antidepressants (10.2%), and opioids (7.6%). Poisoning rates were highest at ages
      16-18 years for females and 19-24 years for males. Opioid poisonings increased
      fivefold from 1998-2014 (females: aIRR 5.30, 95% confidence interval (CI) = 4.08
      to 6.89; males: aIRR 5.11, 95% CI = 3.37 to 7.76), antidepressant poisonings
      three-to fourfold (females: aIRR 3.91, 95% CI = 3.18 to 4.80, males: aIRR 2.70,
      95% CI = 2.04 to 3.58), aspirin/NSAID poisonings threefold (females: aIRR 2.84,
      95% CI = 2.40 to 3.36, males: aIRR 2.76, 95% CI = 2.05 to 3.72) and paracetamol
      poisonings threefold in females (aIRR 2.87, 95% CI = 2.58 to 3.20). Across all
      substances poisoning incidence was higher in more disadvantaged groups, with the
      strongest gradient for opioid poisonings among males (aIRR 3.46, 95% CI = 2.24 to
      5.36). CONCLUSION: It is important that GPs raise awareness with families of the
      substances young people use to self-harm, especially the common use of over-the
      counter medications. Quantities of medication prescribed to young people at risk
      of self-harm and their families should be limited, particularly analgesics and
      antidepressants.

PMID- 30201831
TI  - The soluble transhydrogenase UdhA affecting the glutamate-dependent acid
      resistance system of Escherichia coli under acetate stress.
AB  - The soluble transhydrogenase (UdhA) is one of two transhydrogenases that play a
      role in maintaining the balance between NAD(H) pools and NADP(H) pools in
      Escherichia coli Although UdhA has been extensively used in metabolic engineering
      and biocatalysis for cofactor regeneration, its role in acid resistance has not
      been reported. Here we used DNA microarray to explore the impact of UdhA on
      transcript levels. We demonstrated that during growth on acetate, the expression
      of genes involved in the respiratory chain and Gad acid resistance system was
      inhibited in the udhA-knockout strain. The deletion of udhA significantly
      repressed the expression of six genes (gadA, gadB, gadC, gadE, hdeA and hdeB)
      which are involved in Gad acid resistance and resulted in low survival of the
      bacterium at a low pH of 4.9. Moreover, UdhA was essential for NADH production
      which is important for the adaptive growth of E. coli on acetate, while NADH
      concentration in the udhA-knockout strain was quite low and supplemental NADH
      significantly increased the expression of acid resistance genes and survival of
      the udhA-knockout strain. These results demonstrated that UdhA is an important
      source of NADH of E. coli growth on acetate and affects Gad acid resistance
      system under acetate stress.

PMID- 30201832
TI  - Connectome to behaviour: modelling Caenorhabditis elegans at cellular resolution.
AB  - It has been 30 years since the 'mind of the worm' was published in Philosophical
      Transactions B (White et al 1986 Phil. Trans. R. Soc. Lond. B314, 1-340).
      Predicting Caenorhabditis elegans' behaviour from its wiring diagram has been an
      enduring challenge since then. This special theme issue of Philosophical
      Transactions B combines research from neuroscientists, physicists, mathematicians
      and engineers to discuss advances in neural activity imaging, behaviour
      quantification and multiscale simulations, and how they are bringing the goal of
      whole-animal modelling at cellular resolution within reach.This article is part
      of a discussion meeting issue 'Connectome to behaviour: modelling C. elegans at
      cellular resolution'.

PMID- 30201833
TI  - Clues to basis of exploratory behaviour of the C. elegans snout from head
      somatotropy.
AB  - Wave propagation during locomotory movements of Caenorhabditis elegans is
      constrained to a single dorso/ventral plane. By contrast, the tip of the head
      (snout) can make rapid exploratory movements in all directions relative to the
      body axis. These extra degrees of freedom are probably important for animals to
      seek and identify desirable passages in the interstices of the three-dimensional
      matrix of soil particles, their usual habitat. The differences in degrees of
      freedom of movement between snout and body are reflected in the innervation of
      the musculature. Along the length of the body, the two quadrants of dorsal muscle
      receive common innervation as do the two quadrants of ventral muscle. By
      contrast, muscles in the snout have an octagonal arrangement of innervation. It
      is likely that the exploratory behaviour of the snout is mediated by octant
      specific motor and sensory neurons, together with their associated interneurons.
      The well-defined anatomical structure and neural circuitry of the snout together
      with behavioural observations should facilitate the implementation of models of
      the neural basis of exploratory movements, which could lead to an understanding
      of the basis of this relatively complex behaviour, a behaviour that has
      similarities to foraging in some vertebrates.This article is part of a discussion
      meeting issue 'Connectome to behaviour: modelling C. elegans at cellular
      resolution'.

PMID- 30201834
TI  - Neuropeptides encoded by nlp-49 modulate locomotion, arousal and egg-laying
      behaviours in Caenorhabditis elegans via the receptor SEB-3.
AB  - Neuropeptide signalling has been implicated in a wide variety of biological
      processes in diverse organisms, from invertebrates to humans. The Caenorhabditis
      elegans genome has at least 154 neuropeptide precursor genes, encoding over 300
      bioactive peptides. These neuromodulators are thought to largely signal beyond
      'wired' chemical/electrical synapse connections, therefore creating a 'wireless'
      network for neuronal communication. Here, we investigated how behavioural states
      are affected by neuropeptide signalling through the G protein-coupled receptor
      SEB-3, which belongs to a bilaterian family of orphan secretin receptors. Using
      reverse pharmacology, we identified the neuropeptide NLP-49 as a ligand of this
      evolutionarily conserved neuropeptide receptor. Our findings demonstrate novel
      roles for NLP-49 and SEB-3 in locomotion, arousal and egg-laying. Specifically,
      high-content analysis of locomotor behaviour indicates that seb-3 and nlp-49
      deletion mutants cause remarkably similar abnormalities in movement dynamics,
      which are reversed by overexpression of wild-type transgenes. Overexpression of
      NLP-49 in AVK interneurons leads to heightened locomotor arousal, an effect that
      is dependent on seb-3. Finally, seb-3 and nlp-49 mutants also show constitutive
      egg-laying in liquid medium and alter the temporal pattern of egg-laying in
      similar ways. Together, these results provide in vivo evidence that NLP-49
      peptides act through SEB-3 to modulate behaviour, and highlight the importance of
      neuropeptide signalling in the control of behavioural states.This article is part
      of a discussion meeting issue 'Connectome to behaviour: modelling C. elegans at
      cellular resolution'.

PMID- 30201835
TI  - Caenorhabditis elegans excitatory ventral cord motor neurons derive rhythm for
      body undulation.
AB  - The intrinsic oscillatory activity of central pattern generators underlies motor
      rhythm. We review and discuss recent findings that address the origin of
      Caenorhabditis elegans motor rhythm. These studies propose that the A- and mid
      body B-class excitatory motor neurons at the ventral cord function as non
      bursting intrinsic oscillators to underlie body undulation during reversal and
      forward movements, respectively. Proprioception entrains their intrinsic
      activities, allows phase-coupling between members of the same class motor
      neurons, and thereby facilitates directional propagation of undulations. Distinct
      pools of premotor interneurons project along the ventral nerve cord to innervate
      all members of the A- and B-class motor neurons, modulating their oscillations,
      as well as promoting their bi-directional coupling. The two motor sub-circuits,
      which consist of oscillators and descending inputs with distinct properties, form
      the structural base of dynamic rhythmicity and flexible partition of the forward
      and backward motor states. These results contribute to a continuous effort to
      establish a mechanistic and dynamic model of the C. elegans sensorimotor system.
      C. elegans exhibits rich sensorimotor functions despite a small neuron number.
      These findings implicate a circuit-level functional compression. By integrating
      the role of rhythm generation and proprioception into motor neurons, and the role
      of descending regulation of oscillators into premotor interneurons, this
      numerically simple nervous system can achieve a circuit infrastructure analogous
      to that of anatomically complex systems. C. elegans has manifested itself as a
      compact model to search for general principles of sensorimotor behaviours.This
      article is part of a discussion meeting issue 'Connectome to behaviour: modelling
      C. elegans at cellular resolution'.

PMID- 30201836
TI  - Sensorimotor integration in Caenorhabditis elegans: a reappraisal towards dynamic
      and distributed computations.
AB  - The nematode Caenorhabditis elegans is a tractable model system to study
      locomotion, sensory navigation and decision-making. In its natural habitat, it is
      thought to navigate complex multisensory environments in order to find food and
      mating partners, while avoiding threats like predators or toxic environments.
      While research in past decades has shed much light on the functions and
      mechanisms of selected sensory neurons, we are just at the brink of understanding
      how sensory information is integrated by interneuron circuits for action
      selection in the worm. Recent technological advances have enabled whole-brain
      Ca2+ imaging and Ca2+ imaging of neuronal activity in freely moving worms. A
      common principle emerging across multiple studies is that most interneuron
      activities are tightly coupled to the worm's instantaneous behaviour; notably,
      these observations encompass neurons receiving direct sensory neuron inputs. The
      new findings suggest that in the C. elegans brain, sensory and motor
      representations are integrated already at the uppermost sensory processing
      layers. Moreover, these results challenge a perhaps more intuitive view of
      sequential feed-forward sensory pathways that converge onto premotor interneurons
      and motor neurons. We propose that sensorimotor integration occurs rather in a
      distributed dynamical fashion. In this perspective article, we will explore this
      view, discuss the challenges and implications of these discoveries on the
      interpretation and design of neural activity experiments, and discuss possible
      functions. Furthermore, we will discuss the broader context of similar findings
      in fruit flies and rodents, which suggest generalizable principles that can be
      learnt from this amenable nematode model organism.This article is part of a
      discussion meeting issue 'Connectome to behaviour: modelling C. elegans at
      cellular resolution'.

PMID- 30201838
TI  - From head to tail: a neuromechanical model of forward locomotion in
      Caenorhabditis elegans.
AB  - With 302 neurons and a near-complete reconstruction of the neural and muscle
      anatomy at the cellular level, Caenorhabditis elegans is an ideal candidate
      organism to study the neuromechanical basis of behaviour. Yet despite the breadth
      of knowledge about the neurobiology, anatomy and physics of C. elegans, there are
      still a number of unanswered questions about one of its most basic and
      fundamental behaviours: forward locomotion. How the rhythmic pattern is generated
      and propagated along the body is not yet well understood. We report on the
      development and analysis of a model of forward locomotion that integrates the
      neuroanatomy, neurophysiology and body mechanics of the worm. Our model is
      motivated by experimental analysis of the structure of the ventral cord circuitry
      and the effect of local body curvature on nearby motoneurons. We developed a
      neuroanatomically grounded model of the head motoneuron circuit and the ventral
      nerve cord circuit. We integrated the neural model with an existing biomechanical
      model of the worm's body, with updated musculature and stretch receptors. Unknown
      parameters were evolved using an evolutionary algorithm to match the speed of the
      worm on agar. We performed 100 evolutionary runs and consistently found
      electrophysiological configurations that reproduced realistic control of forward
      movement. The ensemble of successful solutions reproduced key experimental
      observations that they were not designed to fit, including the wavelength and
      frequency of the propagating wave. Analysis of the ensemble revealed that head
      motoneurons SMD and RMD are sufficient to drive dorsoventral undulations in the
      head and neck and that short-range posteriorly directed proprioceptive feedback
      is sufficient to propagate the wave along the rest of the body.This article is
      part of a discussion meeting issue 'Connectome to behaviour: modelling C. elegans
      at cellular resolution'.

PMID- 30201837
TI  - Caenorhabditis elegans and the network control framework-FAQs.
AB  - Control is essential to the functioning of any neural system. Indeed, under
      healthy conditions the brain must be able to continuously maintain a tight
      functional control between the system's inputs and outputs. One may therefore
      hypothesize that the brain's wiring is predetermined by the need to maintain
      control across multiple scales, maintaining the stability of key internal
      variables, and producing behaviour in response to environmental cues. Recent
      advances in network control have offered a powerful mathematical framework to
      explore the structure-function relationship in complex biological, social and
      technological networks, and are beginning to yield important and precise insights
      on neuronal systems. The network control paradigm promises a predictive,
      quantitative framework to unite the distinct datasets necessary to fully describe
      a nervous system, and provide mechanistic explanations for the observed structure
      and function relationships. Here, we provide a thorough review of the network
      control framework as applied to Caenorhabditis elegans (Yan et al. 2017
      Nature550, 519-523. (doi:10.1038/nature24056)), in the style of Frequently Asked
      Questions. We present the theoretical, computational and experimental aspects of
      network control, and discuss its current capabilities and limitations, together
      with the next likely advances and improvements. We further present the Python
      code to enable exploration of control principles in a manner specific to this
      prototypical organism.This article is part of a discussion meeting issue
      'Connectome to behaviour: modelling C. elegans at cellular resolution'.

PMID- 30201839
TI  - Powerful and interpretable behavioural features for quantitative phenotyping of
      Caenorhabditis elegans.
AB  - Behaviour is a sensitive and integrative readout of nervous system function and
      therefore an attractive measure for assessing the effects of mutation or drug
      treatment on animals. Video data provide a rich but high-dimensional
      representation of behaviour, and so the first step of analysis is often some form
      of tracking and feature extraction to reduce dimensionality while maintaining
      relevant information. Modern machine-learning methods are powerful but
      notoriously difficult to interpret, while handcrafted features are interpretable
      but do not always perform as well. Here, we report a new set of handcrafted
      features to compactly quantify Caenorhabditis elegans behaviour. The features are
      designed to be interpretable but to capture as much of the phenotypic differences
      between worms as possible. We show that the full feature set is more powerful
      than a previously defined feature set in classifying mutant strains. We then use
      a combination of automated and manual feature selection to define a core set of
      interpretable features that still provides sufficient power to detect behavioural
      differences between mutant strains and the wild-type. Finally, we apply the new
      features to detect time-resolved behavioural differences in a series of
      optogenetic experiments targeting different neural subsets.This article is part
      of a discussion meeting issue 'Connectome to behaviour: modelling C. elegans at
      cellular resolution'.

PMID- 30201840
TI  - Three-dimensional simulation of the Caenorhabditis elegans body and muscle cells
      in liquid and gel environments for behavioural analysis.
AB  - To better understand how a nervous system controls the movements of an organism,
      we have created a three-dimensional computational biomechanical model of the
      Caenorhabditis elegans body based on real anatomical structure. The body model is
      created with a particle system-based simulation engine known as Sibernetic, which
      implements the smoothed particle-hydrodynamics algorithm. The model includes an
      elastic body-wall cuticle subject to hydrostatic pressure. This cuticle is then
      driven by body-wall muscle cells that contract and relax, whose positions and
      shape are mapped from C. elegans anatomy, and determined from light microscopy
      and electron micrograph data. We show that by using different muscle activation
      patterns, this model is capable of producing C. elegans-like behaviours,
      including crawling and swimming locomotion in environments with different
      viscosities, while fitting multiple additional known biomechanical properties of
      the animal. This article is part of a discussion meeting issue 'Connectome to
      behaviour: modelling C. elegans at cellular resolution'.

PMID- 30201841
TI  - Functional connectomics from neural dynamics: probabilistic graphical models for
      neuronal network of Caenorhabditis elegans.
AB  - We propose an approach to represent neuronal network dynamics as a probabilistic
      graphical model (PGM). To construct the PGM, we collect time series of neuronal
      responses produced by the neuronal network and use singular value decomposition
      to obtain a low-dimensional projection of the time-series data. We then extract
      dominant patterns from the projections to get pairwise dependency information and
      create a graphical model for the full network. The outcome model is a functional
      connectome that captures how stimuli propagate through the network and thus
      represents causal dependencies between neurons and stimuli. We apply our
      methodology to a model of the Caenorhabditis elegans somatic nervous system to
      validate and show an example of our approach. The structure and dynamics of the
      C. elegans nervous system are well studied and a model that generates neuronal
      responses is available. The resulting PGM enables us to obtain and verify
      underlying neuronal pathways for known behavioural scenarios and detect possible
      pathways for novel scenarios.This article is part of a discussion meeting issue
      'Connectome to behaviour: modelling C. elegans at cellular resolution'.

PMID- 30201842
TI  - c302: a multiscale framework for modelling the nervous system of Caenorhabditis
      elegans.
AB  - The OpenWorm project has the ambitious goal of producing a highly detailed in
      silico model of the nematode Caenorhabditis elegans A crucial part of this work
      will be a model of the nervous system encompassing all known cell types and
      connections. The appropriate level of biophysical detail required in the neuronal
      model to reproduce observed high-level behaviours in the worm has yet to be
      determined. For this reason, we have developed a framework, c302, that allows
      different instances of neuronal networks to be generated incorporating varying
      levels of anatomical and physiological detail, which can be investigated and
      refined independently or linked to other tools developed in the OpenWorm
      modelling toolchain.This article is part of a discussion meeting issue
      'Connectome to behaviour: modelling C. elegans at cellular resolution'.

PMID- 30201844
TI  - Towards systematic, data-driven validation of a collaborative, multi-scale model
      of Caenorhabditis elegans.
AB  - The OpenWorm Project is an international open-source collaboration to create a
      multi-scale model of the organism Caenorhabditis elegans At each scale, including
      subcellular, cellular, network and behaviour, this project employs one or more
      computational models that aim to recapitulate the corresponding biological system
      at that scale. This requires that the simulated behaviour of each model be
      compared with experimental data both as the model is continuously refined and as
      new experimental data become available. Here we report the use of SciUnit, a
      software framework for model validation, to attempt to achieve these goals.
      During project development, each model is continuously subjected to data-driven
      'unit tests' that quantitatively summarize model-data agreement, identifying
      modelling progress and highlighting particular aspects of each model that fail to
      adequately reproduce known features of the biological organism and its
      components. This workflow is publicly visible via both GitHub and a web
      application and accepts community contributions to ensure that modelling goals
      are transparent and well-informed.This article is part of a discussion meeting
      issue 'Connectome to behaviour: modelling C. elegans at cellular resolution'.

PMID- 30201843
TI  - Geppetto: a reusable modular open platform for exploring neuroscience data and
      models.
AB  - Geppetto is an open-source platform that provides generic middleware
      infrastructure for building both online and desktop tools for visualizing
      neuroscience models and data and managing simulations. Geppetto underpins a
      number of neuroscience applications, including Open Source Brain (OSB), Virtual
      Fly Brain (VFB), NEURON-UI and NetPyNE-UI. OSB is used by researchers to create
      and visualize computational neuroscience models described in NeuroML and simulate
      them through the browser. VFB is the reference hub for Drosophila melanogaster
      neural anatomy and imaging data including neuropil, segmented neurons, microscopy
      stacks and gene expression pattern data. Geppetto is also being used to build a
      new user interface for NEURON, a widely used neuronal simulation environment, and
      for NetPyNE, a Python package for network modelling using NEURON. Geppetto
      defines domain agnostic abstractions used by all these applications to represent
      their models and data and offers a set of modules and components to integrate,
      visualize and control simulations in a highly accessible way. The platform
      comprises a backend which can connect to external data sources, model
      repositories and simulators together with a highly customizable frontend.This
      article is part of a discussion meeting issue 'Connectome to behaviour: modelling
      C. elegans at cellular resolution'.

PMID- 30201845
TI  - OpenWorm: overview and recent advances in integrative biological simulation of
      Caenorhabditis elegans.
AB  - The adoption of powerful software tools and computational methods from the
      software industry by the scientific research community has resulted in a renewed
      interest in integrative, large-scale biological simulations. These typically
      involve the development of computational platforms to combine diverse, process
      specific models into a coherent whole. The OpenWorm Foundation is an independent
      research organization working towards an integrative simulation of the nematode
      Caenorhabditis elegans, with the aim of providing a powerful new tool to
      understand how the organism's behaviour arises from its fundamental biology. In
      this perspective, we give an overview of the history and philosophy of OpenWorm,
      descriptions of the constituent sub-projects and corresponding open-science
      management practices, and discuss current achievements of the project and future
      directions.This article is part of a discussion meeting issue 'Connectome to
      behaviour: modelling C. elegans at cellular resolution'.

PMID- 30201846
TI  - Signatures of proprioceptive control in Caenorhabditis elegans locomotion.
AB  - Animal neuromechanics describes the coordinated self-propelled movement of a
      body, subject to the combined effects of internal neural control and mechanical
      forces. Here we use a computational model to identify effects of neural and
      mechanical modulation on undulatory forward locomotion of Caenorhabditis elegans,
      with a focus on proprioceptively driven neural control. We reveal a fundamental
      relationship between body elasticity and environmental drag in determining the
      dynamics of the body and demonstrate the manifestation of this relationship in
      the context of proprioceptively driven control. By considering characteristics
      unique to proprioceptive neurons, we predict the signatures of internal gait
      modulation that contrast with the known signatures of externally or
      biomechanically modulated gait. We further show that proprioceptive feedback can
      suppress neuromechanical phase lags during undulatory locomotion, contrasting
      with well studied advancing phase lags that have long been a signature of
      centrally generated, feed-forward control.This article is part of a discussion
      meeting issue 'Connectome to behaviour: modelling C. elegans at cellular
      resolution'.

PMID- 30201847
TI  - Association of Time in Range, as Assessed by Continuous Glucose Monitoring, With
      Diabetic Retinopathy in Type 2 Diabetes.
AB  - OBJECTIVE: Continuous glucose monitoring (CGM) has provided new measures of
      glycemic control that link to diabetes complications. This study investigated the
      association between the time in range (TIR) assessed by CGM and diabetic
      retinopathy (DR). RESEARCH DESIGN AND METHODS: A total of 3,262 patients with
      type 2 diabetes were recruited. TIR was defined as the percentage of time spent
      within the glucose range of 3.9-10.0 mmol/L during a 24-h period. Measures of
      glycemic variability (GV) were assessed as well. DR was determined by using
      fundus photography and graded as 1) non-DR; 2) mild nonproliferative DR (NPDR);
      3) moderate NPDR; or 4) vision-threatening DR (VTDR). RESULTS: The overall
      prevalence of DR was 23.9% (mild NPDR 10.9%, moderate NPDR 6.1%, VTDR 6.9%).
      Patients with more advanced DR had significantly less TIR and higher measures of
      GV (all P for trend <0.01). The prevalence of DR on the basis of severity
      decreased with ascending TIR quartiles (all P for trend <0.001), and the severity
      of DR was inversely correlated with TIR quartiles (r = -0.147; P < 0.001).
      Multinomial logistic regression revealed significant associations between TIR and
      all stages of DR (mild NPDR, P = 0.018; moderate NPDR, P = 0.014; VTDR, P =
      0.019) after controlling for age, sex, BMI, diabetes duration, blood pressure,
      lipid profile, and HbA1c. Further adjustment of GV metrics partially attenuated
      these associations, although the link between TIR and the presence of any DR
      remained significant. CONCLUSIONS: TIR assessed by CGM is associated with DR in
      type 2 diabetes.

PMID- 30201848
TI  - Therapeutic Lifestyle Changes Improve HDL Function by Inhibiting Myeloperoxidase
      Mediated Oxidation in Patients With Metabolic Syndrome.
AB  - OBJECTIVE: Phagocyte-derived myeloperoxidase (MPO) and proinflammatory HDL are
      associated with metabolic syndrome (MetS) and increased cardiovascular disease
      risk. Therapeutic lifestyle changes (TLCs), such as a Mediterranean diet and
      exercise, decrease this risk. However, the link among TLCs, HDL, and MPO-mediated
      oxidative stress remains unclear. RESEARCH DESIGN AND METHODS: In this study, we
      characterized changes in cholesterol efflux capacity (CEC), a metric of HDL
      function; MPO-mediated oxidation; and the HDL proteomic profile in 25 patients
      with MetS who underwent 12 weeks of TLCs. RESULTS: After 12 weeks, before
      significant changes to HDL levels, most MetS components improved as a result of
      the TLCs. CEC was significantly increased, and HDL MPO oxidation products, 3
      chlorotyrosine and 3-nitrotyrosine, were decreased with TLCs. The changes in CEC
      were inversely related to the unit changes in 3-chlorotyrosine after we
      controlled for changes in the other MetS components. TLCs did not remodel the HDL
      proteome. CONCLUSIONS: In summary, TLCs improved HDL function by inhibiting MPO
      mediated oxidative stress even before appreciable changes in HDL levels.

PMID- 30201849
TI  - Combined Immunosuppressive Therapy Induces Remission in Patients With Severe Type
      B Insulin Resistance: A Prospective Cohort Study.
AB  - OBJECTIVE: Type B insulin resistance due to autoantibodies against the insulin
      receptor is characterized by diabetes refractory to massive doses of insulin,
      severe hypercatabolism, hyperandrogenism, and a high mortality rate. We analyzed
      the efficacy of combined immunosuppressive therapy in the management of this
      extreme form of diabetes. RESEARCH DESIGN AND METHODS: We performed a prospective
      cohort study including patients with confirmed insulin receptor autoantibodies,
      monitored for median 72 months (25th, 75th interquartile range 25, 88), and
      treated with rituximab, high-dose pulsed steroids, and cyclophosphamide until
      remission, followed by maintenance therapy with azathioprine. Remission was
      defined as the amelioration of the hyperglycemia and discontinuation of insulin
      and/or normalization of hyperandrogenemia. RESULTS: All data are given as median
      (25th, 75th interquartile range). Twenty-two patients aged 42 (25, 57) years,
      86.4% women, fulfilled inclusion criteria. At baseline, fasting glucose was 307
      (203, 398) mg/dL, HbA1c was 11.8% (9.7, 13.6), total testosterone (women) was 126
      (57, 571) ng/dL (normal 8-60), and daily insulin requirement was 1,775 (863,
      2,700) units. After 5 (4, 6.3) months, 86.4% (19 of 22) of patients achieved
      remission, documented by discontinuation of insulin in all patients, normal
      fasting glucose of 80 (76, 92) mg/dL, HbA1c of 5.5% (5.2, 6), and testosterone
      (women) of 28 (20, 47) ng/dL. During follow-up of 72 (25, 88) months, 13.6% (3 of
      22) of patients developed disease recurrence, occurring 24 (22, 36) months after
      initial remission, which responded to repeated therapy. None of the patients
      died. CONCLUSIONS: Combined immunosuppressive therapy has changed the natural
      history of this disease, from 54% mortality to a curable form of diabetes and, as
      such, should be recommended in patients with type B insulin resistance.

PMID- 30201850
TI  - Near-infrared fluorescent northern blot.
AB  - Northern blot analysis detects RNA molecules immobilized on nylon membranes
      through hybridization with radioactive 32P-labeled DNA or RNA oligonucleotide
      probes. Alternatively, nonradioactive northern blot relies on chemiluminescent
      reactions triggered by horseradish peroxidase (HRP) conjugated probes. The use of
      regulated radioactive material and the complexity of chemiluminescent reactions
      and detection have hampered the adoption of northern blot techniques by the wider
      biomedical research community. Here, we describe a sensitive and straightforward
      nonradioactive northern blot method, which utilizes near-infrared (IR)
      fluorescent dye-labeled probes (irNorthern). We found that irNorthern has a
      detection limit of ~0.05 femtomoles (fmol), which is slightly less sensitive than
      32P-Northern. However, we found that the IR dye-labeled probe maintains the
      sensitivity after multiple usages as well as long-term storage. We also present
      alternative irNorthern methods using a biotinylated DNA probe, a DNA probe
      labeled by terminal transferase, or an RNA probe labeled during in vitro
      transcription. Furthermore, utilization of different IR dyes allows multiplex
      detection of different RNA species. Therefore, irNorthern represents a more
      convenient and versatile tool for RNA detection compared to traditional northern
      blot analysis.

PMID- 30201851
TI  - A G-Quadruplex Structure in the Promoter Region of CLIC4 Functions as a
      Regulatory Element for Gene Expression.
AB  - The differential transcriptional expression of CLIC4 between tumor cells and the
      surrounding stroma during cancer progression has been suggested to have a tumor
      promoting effect. However, little is known about the transcriptional regulation
      of CLIC4. To better understand how this gene is regulated, the promoter region of
      CLIC4 was analyzed. We found that a high GC content near the transcriptional
      start site (TSS) might form an alternative G-quadruplex (G4) structure. Nuclear
      magnetic resonance spectroscopy (NMR) confirmed their formation in vitro. The
      reporter assay showed that one of the G4 structures exerted a regulatory role in
      gene transcription. When the G4-forming sequence was mutated to disrupt the G4
      structure, the transcription activity dropped. To examine whether this G4
      structure actually has an influence on gene transcription in the chromosome, we
      utilized the CRISPR/Cas9 system to edit the G4-forming sequence within the CLIC4
      promoter in the cell genome. The pop-in/pop-out strategy was adopted to isolate
      the precisely-edited A375 cell clone. In CRISPR-modified A375 cell clones whose
      G4 was disrupted, there was a decrease in the endogenous CLIC4 messenger RNA
      (mRNA) expression level. In conclusion, we found that the G4 structure in the
      CLIC4 promoter might play an important role in regulating the level of
      transcription.

PMID- 30201852
TI  - Fabrication and Characterization of an Electrospun PHA/Graphene Silver
      Nanocomposite Scaffold for Antibacterial Applications.
AB  - Many wounds are unresponsive to currently available treatment techniques and
      therefore there is an immense need to explore suitable materials, including
      biomaterials, which could be considered as the crucial factor to accelerate the
      healing cascade. In this study, we fabricated polyhydroxyalkanoate-based
      antibacterial mats via an electrospinning technique. One-pot green synthesized
      graphene-decorated silver nanoparticles (GAg) were incorporated into the fibres
      of poly-3 hydroxybutarate-co-12 mol.% hydroxyhexanoate (P3HB-co-12 mol.% HHx), a
      co-polymer of the polyhydroxyalkanoate (PHA) family which is highly
      biocompatible, biodegradable, and flexible in nature. The synthesized PHA/GAg
      biomaterial has been characterized by field emission scanning electron microscopy
      (FESEM), elemental mapping, thermogravimetric analysis (TGA), UV-visible
      spectroscopy (UV-vis), and Fourier transform infrared spectroscopy (FTIR). An in
      vitro antibacterial analysis was performed to investigate the efficacy of PHA/GAg
      against gram-positive Staphylococcus aureus (S. aureus) strain 12,600 ATCC and
      gram-negative Escherichia coli (E. coli) strain 8739 ATCC. The results indicated
      that the PHA/GAg demonstrated significant reduction of S. aureus and E. coli as
      compared to bare PHA or PHA- reduced graphene oxide (rGO) in 2 h of time. The p
      value (p < 0.05) was obtained by using a two-sample t-test distribution.

PMID- 30201853
TI  - Pre-Sleep Consumption of Casein and Whey Protein: Effects on Morning Metabolism
      and Resistance Exercise Performance in Active Women.
AB  - Consuming milk proteins (casein (CP) and whey (WP)) at night before sleep has
      been shown to positively influence next morning resting metabolic rate (RMR). No
      data exist regarding the effect of pre-sleep consumption of CP and WP on the
      ability to perform resistance exercise (RE) the following morning. The present
      study compared the effects of low (24 g) and high (48 g) doses of CP and WP and a
      non-energetic placebo (PLA) consumed 30 min before sleep on morning RMR, and RE
      performance. Nine active women participated in this randomized, double-blind,
      crossover study. Next morning RMR was measured via indirect calorimetry. RE was
      performed on six machines for 2 sets of 10 repetitions, and a 3rd set to failure
      at 60% of one-repetition maximum to calculate RE volume (weight lifted * sets *
      repetitions). Magnitude based inferences were used. Compared to the PLA, 48 g CP
      had a likely increase in RMR (4.0 +/- 4.8%) and possibly trivial (1.1 +/- 7.0%)
      effect on RE volume. There were no clear effects of 24 g CP, 24 g and 48 g of WP
      on RMR and RE volume. In conclusion, 48 g CP elicited favorable changes in
      morning RMR, with only trivial changes in RE performance.

PMID- 30201854
TI  - Target Recognition of SAR Images via Matching Attributed Scattering Centers with
      Binary Target Region.
AB  - A target recognition method of synthetic aperture radar (SAR) images is proposed
      via matching attributed scattering centers (ASCs) to binary target regions. The
      ASCs extracted from the test image are predicted as binary regions. In detail,
      each ASC is first transformed to the image domain based on the ASC model.
      Afterwards, the resulting image is converted to a binary region segmented by a
      global threshold. All the predicted binary regions of individual ASCs from the
      test sample are mapped to the binary target regions of the corresponding
      templates. Then, the matched regions are evaluated by three scores which are
      combined as a similarity measure via the score-level fusion. In the
      classification stage, the target label of the test sample is determined according
      to the fused similarities. The proposed region matching method avoids the
      conventional ASC matching problem, which involves the assignment of ASC sets. In
      addition, the predicted regions are more robust than the point features. The
      Moving and Stationary Target Acquisition and Recognition (MSTAR) dataset is used
      for performance evaluation in the experiments. According to the experimental
      results, the method in this study outperforms some traditional methods reported
      in the literature under several different operating conditions. Under the
      standard operating condition (SOC), the proposed method achieves very good
      performance, with an average recognition rate of 98.34%, which is higher than the
      traditional methods. Moreover, the robustness of the proposed method is also
      superior to the traditional methods under different extended operating conditions
      (EOCs), including configuration variants, large depression angle variation, noise
      contamination, and partial occlusion.

PMID- 30201855
TI  - Biogenic Polyphosphate Nanoparticles from a Marine Cyanobacterium Synechococcus
      sp. PCC 7002: Production, Characterization, and Anti-Inflammatory Properties In
      Vitro.
AB  - Probiotic-derived polyphosphates have attracted interest as potential therapeutic
      agents to improve intestinal health. The current study discovered the
      intracellular accumulation of polyphosphates in a marine cyanobacterium
      Synechococcus sp. PCC 7002 as nano-sized granules. The maximum accumulation of
      polyphosphates in Synechococcus sp. PCC 7002 was found at the late logarithmic
      growth phase when the medium contained 0.74 mM of KH2PO4, 11.76 mM of NaNO3, and
      30.42 mM of Na2SO4. Biogenic polyphosphate nanoparticles (BPNPs) were obtained
      intact from the algae cells by hot water extraction, and were purified to remove
      the organic impurities by Sephadex G-100 gel filtration. By using 100 kDa
      ultrafiltration, BPNPs were fractionated into the larger and smaller populations
      with diameters ranging between 30-70 nm and 10-30 nm, respectively. 4',6
      diamidino-2-phenylindole fluorescence and orthophosphate production revealed that
      a minor portion of BPNPs (about 14-18%) were degraded during simulated
      gastrointestinal digestion. In vitro studies using lipopolysaccharide-activated
      RAW264.7 cells showed that BPNPs inhibited cyclooxygenase-2, inducible nitric
      oxide (NO) synthase expression, and the production of proinflammatory mediators,
      including NO, tumor necrosis factor-alpha, interleukin-6, and interleukin-1beta
      through suppressing the Toll-like receptor 4/NF-kappaB signaling pathway.
      Overall, there is promise in the use of the marine cyanobacterium Synechococcus
      sp. PCC 7002 to produce BPNPs, an anti-inflammatory postbiotic.

PMID- 30201856
TI  - Spatial Patterns in Rush-Hour vs. Work-Week Diesel-Related Pollution across a
      Downtown Core.
AB  - Despite advances in monitoring and modelling of intra-urban variation in multiple
      pollutants, few studies have attempted to separate spatial patterns by time of
      day, or incorporated organic tracers into spatial monitoring studies. Due to
      varying emissions sources from diesel and gasoline vehicular traffic, as well as
      within-day temporal variation in source mix and intensity (e.g., rush-hours vs.
      full-day measures), accurately assessing diesel-related air pollution within an
      urban core can be challenging. We allocated 24 sampling sites across downtown
      Pittsburgh, Pennsylvania (2.8 km2) to capture fine-scale variation in diesel
      related pollutants, and to compare these patterns by sampling interval (i.e.,
      "rush-hours" vs. "work-week" concentrations), and by season. Using geographic
      information system (GIS)-based methods, we allocated sampling sites to capture
      spatial variation in key traffic-related pollution sources (i.e., truck, bus,
      overall traffic densities). Programmable monitors were used to collect integrated
      work-week and rush-hour samples of fine particulate matter (PM2.5), black carbon
      (BC), trace elements, and diesel-related organics (polycyclic aromatic
      hydrocarbons (PAHs), hopanes, steranes), in summer and winter 2014. Land use
      regression (LUR) models were created for PM2.5, BC, total elemental carbon (EC),
      total organic carbon (OC), elemental (Al, Ca, Fe), and organic constituents
      (total PAHs, total hopanes), and compared by sampling interval and season. We
      hypothesized higher pollution concentrations and greater spatial contrast in rush
      hour, compared to full work-week samples, with variation by season and pollutant.
      Rush-hour sampling produced slightly higher total PM2.5 and BC concentrations in
      both seasons, compared to work-week sampling, but no evident difference in
      spatial patterns. We also found substantial spatial variability in most trace
      elements and organic compounds, with comparable spatial patterns using both
      sampling paradigms. Overall, we found higher concentrations of traffic-related
      trace elements and organic compounds in rush-hour samples, and higher
      concentrations of coal-related elements (e.g., As, Se) in work-week samples. Mean
      bus density was the strongest LUR predictor in most models, in both seasons,
      under each sampling paradigm. Within each season and constituent, the bus-related
      terms explained similar proportions of variance in the rush-hour and work-week
      samples. Rush-hour and work-week LUR models explained similar proportions of
      spatial variation in pollutants, suggesting that the majority of emissions may be
      produced during rush-hour traffic across downtown. Results suggest that rush-hour
      emissions may predominantly shape overall spatial variance in diesel-related
      pollutants.

PMID- 30201858
TI  - Are Long-Chain Polyunsaturated Fatty Acids the Link between the Immune System and
      the Microbiome towards Modulating Cancer?
AB  - Three recent studies revealed synergy between immune-checkpoint inhibitors and
      the microbiome as a new approach in the treatment of cancer. Incidentally, there
      has been significant progress in understanding the role of polyunsaturated fatty
      acids (PUFAs) in modulating cancer and the immune system, as well as in
      regulating the microbiome. Inflammation seems to be the common denominator among
      these seemingly unrelated biological entities-immune system, the microbiome, and
      long-chain polyunsaturated fatty acids (LC-PUFAs). This commentary presents a
      hypothesis proposing the existence of an optimal level of LC-PUFAs that nurtures
      the suitable gut microbiota preventing dysbiosis. This synergy between optimal LC
      PUFAs and gut microbiota helps the immune system overcome the immunosuppressive
      tumour microenvironment including enhancing the efficacy of immune checkpoint
      inhibitors. A model on how LC-PUFAs (such as omega(n)-3 and n-6 fatty acids)
      forms a synergistic triad with the immune system and the microbiome in regulating
      inflammation to maintain homeostasis is presented. The principles underlying the
      hypothesis provide a basis in managing and even preventing cancer and other
      chronic diseases associated with inflammation.

PMID- 30201860
TI  - Gluten-Free Diet: From Development to Assessment of a Check-List Designed for the
      Prevention of Gluten Cross-Contamination in Food Services.
AB  - Gluten cross-contamination in gluten-free food may jeopardize treatment of celiac
      patients. Considering the deficit of appropriate instruments to enable the
      implementation of safe production practices for gluten-free food, this study
      aimed to evaluate the application of a check-list elaborated for gluten cross
      contamination prevention in food services. The instrument was applied in 60
      Brazilian food services. Interobserver reproducibility and internal consistency
      of the check-list were tested. A score classification was created for
      establishments according to the food contamination risk assessment. Subsequent to
      the application and statistical analysis, the original instrument was reduced to
      a 30-item check-list. In the reproducibility analysis, none of the 30 items
      showed significant divergence among the evaluators (p > 0.05 in the Cochran Q
      test). The 30-item version of the check-list presented Kuder-Richardson Formula
      20 (KR-20) = 0.771, indicating good internal consistency. The proposed
      classification score is obtained by adding 1 point for each item with an
      "adequate" response; therefore, the final score may vary between 0 and 30 points.
      Establishments with up to 15 points exhibit risk of gluten contamination, while
      establishments with a score above 16 points exhibit low risk of contamination.
      The check-list displayed good reproducibility and internal consistency,
      suggesting that it could be a useful gluten contamination control instrument in
      food services.

PMID- 30201859
TI  - Multiple Aspects of PIP2 Involvement in C. elegans Gametogenesis.
AB  - One of the most studied phosphoinositides is phosphatidylinositol 4,5
      bisphosphate (PIP2), which localizes to the plasma membrane, nuclear speckles,
      small foci in the nucleoplasm, and to the nucleolus in mammalian cells. Here, we
      show that PIP2 also localizes to the nucleus in prophase I, during the
      gametogenesis of C. elegans hermaphrodite. The depletion of PIP2 by type I PIP
      kinase (PPK-1) kinase RNA interference results in an altered chromosome structure
      and leads to various defects during meiotic progression. We observed a decreased
      brood size and aneuploidy in progeny, defects in synapsis, and crossover
      formation. The altered chromosome structure is reflected in the increased
      transcription activity of a tightly regulated process in prophase I. To elucidate
      the involvement of PIP2 in the processes during the C. elegans development, we
      identified the PIP2-binding partners, leucine-rich repeat (LRR-1) protein and
      proteasome subunit beta 4 (PBS-4), pointing to its involvement in the ubiquitin
      proteasome pathway.

PMID- 30201861
TI  - Earable POCER: Development of a Point-of-Care Ear Sensor for Respiratory Rate
      Measurement.
AB  - We have carried out research and development on an earphone-type respiratory rate
      measuring device, earable POCER. The name earable POCER is a combination of
      "earable", which is a word coined from "wearable" and "ear", and "POCER", which
      is an acronym for "point-of-care ear sensor for respiratory rate measurement".
      The earable POCER calculates respiratory frequency, based on the measurement
      values over one minute, through the simple attachment of an ear sensor to one ear
      of the measured subject and displays these on a tablet terminal. The earable
      POCER irradiates infrared light using a light-emitting diode (LED) loaded on an
      ear sensor to the epidermis within the ear canal and, by receiving that reflected
      light with a phototransistor, it measures movement of the ear canal based on
      respiration. In an evaluation experiment, eight healthy subjects first breathed
      through the nose 12 times per minute, then 16 times per minute, and finally 20
      times per minute, in accordance with the flashing of a timing instruction LED.
      The results of these evaluation tests showed that the accuracy of the respiratory
      frequency was 100% for nose breathing 12 times per minute, 93.8% at 16 times, and
      93.8% at 20 times.

PMID- 30201857
TI  - Susceptibility Genes to Plant Viruses.
AB  - Plant viruses use cellular factors and resources to replicate and move. Plants
      respond to viral infection by several mechanisms, including innate immunity,
      autophagy, and gene silencing, that viruses must evade or suppress. Thus, the
      establishment of infection is genetically determined by the availability of host
      factors necessary for virus replication and movement and by the balance between
      plant defense and viral suppression of defense responses. Host factors may have
      antiviral or proviral activities. Proviral factors condition susceptibility to
      viruses by participating in processes essential to the virus. Here, we review
      current advances in the identification and characterization of host factors that
      condition susceptibility to plant viruses. Host factors with proviral activity
      have been identified for all parts of the virus infection cycle: viral RNA
      translation, viral replication complex formation, accumulation or activity of
      virus replication proteins, virus movement, and virion assembly. These factors
      could be targets of gene editing to engineer resistance to plant viruses.

PMID- 30201862
TI  - Inhibition of Wnt3a/FOXM1/beta-Catenin Axis and Activation of GSK3beta and
      Caspases are Critically Involved in Apoptotic Effect of Moracin D in Breast
      Cancers.
AB  - Although Moracin D derived from Morus alba was known to have anti-inflammatory
      and antioxidant activities, the underlying antitumor mechanism of Moracin D has
      not been unveiled thus far. Thus, in the recent study, the apoptotic mechanism of
      Moracin D was elucidated in breast cancer cells. Herein, Moracin D exerted
      significant cytotoxicity in MDA-MB-231 and MCF-7 cells. Furthermore, Moracin D
      increased sub G1 population; cleaved poly (Adenosine diphosphate (ADP-ribose))
      polymerase (PARP); activated cysteine aspartyl-specific protease 3 (caspase 3);
      and attenuated the expression of c-Myc, cyclin D1, B-cell lymphoma 2 (Bcl-2), and
      X-linked inhibitor of apoptosis protein (XIAP) in MDA-MB231 cells. Of note,
      Moracin D reduced expression of Forkhead box M1 (FOXM1), beta-catenin, Wnt3a, and
      upregulated glycogen synthase kinase 3 beta (GSK3beta) on Tyr216 along with
      disturbed binding of FOXM1 with beta-catenin in MDA-MB-231 cells. Conversely,
      GSK3beta inhibitor SB216763 reversed the apoptotic ability of Moracin D to reduce
      expression of FOXM1, beta-catenin, pro-caspase3, and pro-PARP in MDA-MB-231
      cells. Overall, these findings provide novel insight that Moracin D inhibits
      proliferation and induces apoptosis via suppression of Wnt3a/FOXM1/beta-catenin
      signaling and activation of caspases and GSK3beta.

PMID- 30201863
TI  - Structural Basis for the Lipopolysaccharide Export Activity of the Bacterial
      Lipopolysaccharide Transport System.
AB  - Gram-negative bacteria have a dense outer membrane (OM) coating of
      lipopolysaccharides, which is essential to their survival. This coating is
      assembled by the LPS (lipopolysaccharide) transport (Lpt) system, a coordinated
      seven-subunit protein complex that spans the cellular envelope. LPS transport is
      driven by an ATPase-dependent mechanism dubbed the "PEZ" model, whereby a
      continuous stream of LPS molecules is pushed from subunit to subunit. This review
      explores recent structural and functional findings that have elucidated the
      subunit-scale mechanisms of LPS transport, including the novel ABC-like mechanism
      of the LptB2FG subcomplex and the lateral insertion of LPS into the OM by LptD/E.
      New questions are also raised about the functional significance of LptA
      oligomerization and LptC. The tightly regulated interactions between these
      connected subcomplexes suggest a pathway that can react dynamically to membrane
      stress and may prove to be a valuable target for new antibiotic therapies for
      Gram-negative pathogens.

PMID- 30201864
TI  - Edge Computing Based IoT Architecture for Low Cost Air Pollution Monitoring
      Systems: A Comprehensive System Analysis, Design Considerations & Development.
AB  - With the swift growth in commerce and transportation in the modern civilization,
      much attention has been paid to air quality monitoring, however existing
      monitoring systems are unable to provide sufficient spatial and temporal
      resolutions of the data with cost efficient and real time solutions. In this
      paper we have investigated the issues, infrastructure, computational complexity,
      and procedures of designing and implementing real-time air quality monitoring
      systems. To daze the defects of the existing monitoring systems and to decrease
      the overall cost, this paper devised a novel approach to implement the air
      quality monitoring system, employing the edge-computing based Internet-of-Things
      (IoT). In the proposed method, sensors gather the air quality data in real time
      and transmit it to the edge computing device that performs necessary processing
      and analysis. The complete infrastructure & prototype for evaluation is developed
      over the Arduino board and IBM Watson IoT platform. Our model is structured in
      such a way that it reduces the computational burden over sensing nodes (reduced
      to 70%) that is battery powered and balanced it with edge computing device that
      has its local data base and can be powered up directly as it is deployed indoor.
      Algorithms were employed to avoid temporary errors in low cost sensor, and to
      manage cross sensitivity problems. Automatic calibration is set up to ensure the
      accuracy of the sensors reporting, hence achieving data accuracy around 75-80%
      under different circumstances. In addition, a data transmission strategy is
      applied to minimize the redundant network traffic and power consumption. Our
      model acquires a power consumption reduction up to 23% with a significant low
      cost. Experimental evaluations were performed under different scenarios to
      validate the system's effectiveness.

PMID- 30201865
TI  - Structural and Stress Properties of AlGaN Epilayers Grown on AlN-Nanopatterned
      Sapphire Templates by Hydride Vapor Phase Epitaxy.
AB  - In this paper, we report the epitaxial growth and material characteristics of
      AlGaN (Al mole fraction of 10%) on an AlN/nanopatterned sapphire substrate (NPSS)
      template by hydride vapor phase epitaxy (HVPE). The crystalline quality, surface
      morphology, microstructure, and stress state of the AlGaN/AlN/NPSS epilayers were
      investigated using X-ray diffraction (XRD), atomic force microscopy (AFM), and
      transmission electron microscopy (TEM). The results indicate that the crystal
      quality of the AlGaN film could be improved when grown on the AlN/NPSS template.
      The screw threading dislocation (TD) density was reduced to 1.4 * 108 cm-2 for
      the AlGaN epilayer grown on the AlN/NPSS template, which was lower than that of
      the sample grown on a flat c-plane sapphire substrate (6.3 * 108 cm-2). As
      examined by XRD measurements, the biaxial tensile stress of the AlGaN film was
      significantly reduced from 1,187 MPa (on AlN/NPSS) to 38.41 MPa (on flat c-plane
      sapphire). In particular, an increase of the Al content in the overgrown AlGaN
      layer was confirmed by the TEM observation. This could be due to the relaxation
      of the in-plane stress through the AlGaN and AlN/NPSS template interface.

PMID- 30201867
TI  - The Protective Effect of a Long-Acting and Multi-Target HM-3-Fc Fusion Protein in
      Rheumatoid Arthritis.
AB  - Current treatment of rheumatoid arthritis (RA) is limited by relative shortage of
      treatment targets. HM-3 is a novel anti-RA polypeptide consisting of 18 amino
      acids with integrin alphaVbeta3 and alpha5beta1 as targets. Previous studies
      confirmed that HM-3 effectively inhibited the synovial angiogenesis and the
      inflammatory response. However, due to its short half-life, the anti-RA activity
      was achieved by frequent administration. To extend the half-life of HM-3, we
      designed a fusion protein with name HM-3-Fc, by combination of modified Fc
      segment of immunoglobulin 4 (IgG4) with HM-3 polypeptide. In vitro cell
      experiments demonstrated that HM-3-Fc inhibited the proliferation of splenic
      lymphocytes and reduced the release of TNF-alpha from macrophages. The
      pharmacodynamics studies on mice paw in Collagen-Induced Arthritis (CIA) model
      demonstrated that HM-3-Fc administered once in 5 days in the 50 and 25 mg/kg
      groups, or once in 7 days in the 25 mg/kg group showed a better protective effect
      within two weeks than the positive control adalimumab and HM-3 group. Preliminary
      pharmacokinetic studies in cynomolgus confirmed that the in vivo half-life of HM
      3-Fc was 15.24 h in comparison with 1.32 min that of HM-3, which demonstrated
      that an Fc fusion can effectively increase the half-life of HM-3 and make it
      possible for further reduction of subcutaneous injection frequency. Fc-HM-3 is a
      long-acting active molecule for RA treatment.

PMID- 30201866
TI  - Widespread Expression of Hedgehog Pathway Components in a Large Panel of Human
      Tumor Cells and Inhibition of Tumor Growth by GANT61: Implications for Cancer
      Therapy.
AB  - The sonic Hedgehog/GLI signaling pathway (HH) is critical for maintaining tissue
      polarity in development and contributes to tumor stemness. Transcription factors
      GLI1-3 are the downstream effectors of HH and activate oncogenic targets. To
      explore the completeness of the expression of HH components in tumor cells, we
      performed a screen for all HH proteins in a wide spectrum of 56 tumor cell lines
      of various origin using Western blot analysis. Generally, all HH proteins were
      expressed. Important factors GLI1 and GLI2 were always expressed, only
      exceptionally one of them was lowered, suggesting the functionality of HH in all
      tumors tested. We determined the effect of a GLI inhibitor GANT61 on
      proliferation in 16 chosen cell lines. More than half of tumor cells were
      sensitive to GANT61 to various extents. GANT61 killed the sensitive cells through
      apoptosis. The inhibition of reporter activity containing 12xGLI consensus sites
      by GANT61 and cyclopamine roughly correlated with cell proliferation influenced
      by GANT61. Our results recognize the sensitivity of tumor cell types to GANT61 in
      cell culture and support a critical role for GLI factors in tumor progression
      through restraining apoptosis. The use of GANT61 in combined targeted therapy of
      sensitive tumors, such as melanomas, seems to be immensely helpful.

PMID- 30201868
TI  - Graphene Oxide-Silver Nanoparticles in Molecularly-Imprinted Hybrid Films
      Enabling SERS Selective Sensing.
AB  - A highly sensitive and selective Raman sensor has been developed by combining
      molecularly imprinted cavities, silver nanoparticles, and graphene oxide into a
      hybrid organic-inorganic film. The molecular imprinted nanocomposite material is
      an advanced platform that exhibits Graphene-mediated Surface-Enhanced Raman
      Scattering. The sensing layers have been prepared via sol-gel process and
      imprinted with rhodamine 6G to obtain selective dye recognition. Graphene oxide
      sheets decorated with silver nanoparticles have been incorporated into the matrix
      to enhance the Raman scattering signal. The template molecule can be easily
      removed from the films by ultrasonication in ethanol. A 712-fold Raman
      enhancement has been observed, which corresponds to a 2.15 * 1013 count.MUmol-1
      signal enhancement per molecular cavity. Besides Raman enhancement, the sensing
      platform has shown an excellent selectivity toward the test molecule with respect
      to similar dyes. In addition, the material can be reused at least 10 times
      without any loss of performance.

PMID- 30201869
TI  - In Vitro Anthelmintic Activity of Four Plant-Derived Compounds against Sheep
      Gastrointestinal Nematodes.
AB  - By using the egg hatch test (EHT), the larval development test (LDT) and the
      larval mortality/paralysis test (LMT), the in vitro anthelmintic activity on
      sheep gastrointestinal strongyles (GIS) of four plant-derived pure compounds,
      mangiferin (at 0.25%, 0.125% and 0.0625%), rutin (at 1%, 0.75%, 0.5%), quercetin
      (at 1%), and beta-sitosterol (at 1%, 0.75%, 0.5%), was investigated. For
      comparison, untreated and treated (0.1% thiabendazole, 0.1% TBZ) controls were
      used. Six repetitions were made throughout the experiment. Data were
      statistically elaborated using the chi2 test. The concentration able to inhibit
      the development of the 50% of L1s to L3s and causing the mortality of the 50% of
      L3s (EC50) was also calculated. L3s recovered from untreated Petri dishes were
      identified at the genus level. In EHT, all tested compounds at all concentrations
      significantly (p < 0.01) inhibited the hatch of the eggs when compared to the
      untreated controls, but none of them was as effective as 0.1% TBZ. In LDT, rutin
      (at 1%, 0.75% and 0.5%), mangiferin (at 0.25% and 0.125%), beta-sitosterol (at
      1%) and 0.1% TBZ completely prevented the larval development from L1 to L3 in
      respect to the untreated controls (p < 0.01). In LMT, all tested compounds
      significantly (p < 0.01) increased the death of L3s compared to the untreated
      controls, except for beta-sitosterol at 0.5%. However, only rutin at all
      concentrations and 0.25% and 0.125% mangiferin were as effective as 0.1% TBZ.
      Haemonchus, Trichostrongylus, Chabertia and Teladorsagia/Ostertagia GIS genera,
      were identified.

PMID- 30201870
TI  - Independently Tunable Fano Resonances Based on the Coupled Hetero-Cavities in a
      Plasmonic MIM System.
AB  - In this paper, based on coupled hetero-cavities, multiple Fano resonances are
      produced and tuned in a plasmonic metal-insulator-metal (MIM) system. The
      structure comprises a rectangular cavity, a side-coupled waveguide, and an upper
      coupled circular cavity with a metal-strip core, used to modulate Fano
      resonances. Three Fano resonances can be realized, which originate from
      interference of the cavity modes between the rectangular cavity and the metal
      strip-core circular cavity. Due to the different cavity-cavity coupling
      mechanisms, the three Fano resonances can be divided into two groups, and each
      group of Fano resonances can be well tuned independently by changing the
      different cavity parameters, which can allow great flexibility to control
      multiple Fano resonances in practice. Furthermore, through carefully adjusting
      the direction angle of the metal-strip core in the circular cavity, the position
      and lineshape of the Fano resonances can be easily tuned. Notably, reversal
      asymmetry takes place for one of the Fano resonances. The influence of the
      direction angle on the figure of merit (FOM) value is also investigated. A
      maximum FOM of 3436 is obtained. The proposed structure has high transmission,
      sharp Fano lineshape, and high sensitivity to change in the background refractive
      index. This research provides effective guidance to tune multiple Fano
      resonances, which has important applications in nanosensors, filters, modulators,
      and other related plasmonic devices.

PMID- 30201871
TI  - Current Trends in Metallic Orthopedic Biomaterials: From Additive Manufacturing
      to Bio-Functionalization, Infection Prevention, and Beyond.
AB  - There has been a growing interest in metallic biomaterials during the last five
      years, as recent developments in additive manufacturing (=3D printing), surface
      bio-functionalization techniques, infection prevention strategies, biodegradable
      metallic biomaterials, and composite biomaterials have provided many
      possibilities to develop biomaterials and medical devices with unprecedented
      combinations of favorable properties and advanced functionalities. Moreover,
      development of biomaterials is no longer separated from the other branches of
      biomedical engineering, particularly tissue biomechanics, musculoskeletal
      dynamics, and image processing aspects of skeletal radiology. In this editorial,
      I will discuss all the above-mentioned topics, as they constitute some of the
      most important trends of research on metallic biomaterials. This editorial will,
      therefore, serve as a foreword to the papers appearing in a special issue
      covering the current trends in metallic biomaterials.

PMID- 30201872
TI  - Melatonin Sensitizes Hepatocellular Carcinoma Cells to Chemotherapy Through Long
      Non-Coding RNA RAD51-AS1-Mediated Suppression of DNA Repair.
AB  - DNA repair systems are abnormally active in most hepatocellular carcinoma (HCC)
      cells due to accumulated mutations, resulting in elevated DNA repair capacity and
      resistance to chemotherapy and radiotherapy. Thus, targeting DNA repair
      mechanisms is a common treatment approach in HCC to sensitize cancer cells to DNA
      damage. In this study, we examined the anti-HCC effects of melatonin and
      elucidated the regulatory mechanisms. The results of functional assays showed
      that in addition to inhibiting the proliferation, migration, and invasion
      abilities of HCC cells, melatonin suppressed their DNA repair capacity, thereby
      promoting the cytotoxicity of chemotherapy and radiotherapy. Whole-transcriptome
      and gain- and loss-of-function analyses revealed that melatonin induces
      expression of the long noncoding RNA RAD51-AS1, which binds to RAD51 mRNA to
      inhibit its translation, effectively decreasing the DNA repair capacity of HCC
      cells and increasing their sensitivity to chemotherapy and radiotherapy. Animal
      models further demonstrated that a combination of melatonin and the
      chemotherapeutic agent etoposide (VP16) can significantly enhance tumor growth
      inhibition compared with monotherapy. Our results show that melatonin is a
      potential adjuvant treatment for chemotherapy and radiotherapy in HCC.

PMID- 30201873
TI  - Evolution of Tembusu Virus in Ducks, Chickens, Geese, Sparrows, and Mosquitoes in
      Northern China.
AB  - Tembusu virus (TMUV) is a contagious pathogen from fowl that mainly infects ducks
      and geese, causing symptoms of high fever, loss of appetite, retarded growth,
      neurological symptoms, severe duck-drop syndrome, and even death. During an
      epidemiological investigation of TMUV in Northern China, we isolated 11 TMUV
      strains from ducks, chickens, geese, sparrows, and mosquitoes (2011-2017).
      Phylogenetic analysis of the open-reading frames of genes revealed that these
      strains clustered into Chinese strains II. The nucleotide and amino acid
      homologies of NS1 of the strains ranged between 85.8-99.8% and 92.5-99.68%,
      respectively, which were lower than those of E (86.7-99.9% and 96.5-99.9%,
      respectively), NS3 (87.6-99.9% and 98.2-99.8%, respectively), and NS5 (86.5-99.9%
      and 97.8-99.9%, respectively). Predictions of the tertiary structure of the viral
      proteins indicated that NS1 in 4 of 11 strains had a protein structure mutation
      at 180TAV182 that changed a random crimp into an alpha helix. The protein of 6 of
      11 strains had a glycosylation site mutation from NTTD to NITD. Furthermore,
      epidemiological data suggested that TMUV has been circulating in half of China's
      provinces (17 of 34). Our findings, for the first time, have identified the NS1
      protein as a potential hypervariable region for genetic evolution. Additionally,
      the territorial scope of the virus has expanded, requiring strict bio-security
      measures or a multivalent vaccine to control its spread.

PMID- 30201874
TI  - Uremic Toxins Activates Na/K-ATPase Oxidant Amplification Loop Causing Phenotypic
      Changes in Adipocytes in In Vitro Models.
AB  - BACKGROUND: Oxidant stress plays a key role in the development of chronic kidney
      disease (CKD). Experimental CKD leads to accumulation of uremic toxins (UT) in
      the circulation resulting in increased ROS production, which in turn, is known to
      activate the Na/K-ATPase/ROS amplification loop. Studies in a murine model of
      obesity have shown that increased oxidative stress in plasma is due to increased
      ROS and cytokine production from dysfunctional adipocytes. Therefore, we
      hypothesized that adipocytes exposed to UTs will activate the Na/K-ATPase oxidant
      amplification loop causing redox imbalance and phenotypic alterations in
      adipocytes. We also aimed to demonstrate that the Na/K-ATPase signaling
      antagonist, pNaKtide, attenuates these pathophysiological consequences. METHODS:
      In the first set of experiments, 3T3-L1 murine pre-adipocytes were treated with
      varying concentrations of UTs, indoxyl sulfate (IS) (50, 100 and 250 uM) and p
      cresol (50, 100 and 200 uM), with or without pNaKtide (0.7 uM) for five days in
      adipogenic media, followed by Oil Red O staining to study adipogenesis. RT-PCR
      analysis was performed to study expression of adipogenic, apoptotic and
      inflammatory markers, while DHE staining evaluated the superoxide levels in UT
      treated cells. In a second set of experiments, visceral fat was obtained from the
      West Virginian population. MSCs were isolated and cultured in adipogenic media
      for 14 days, which was treated with indoxyl sulfate (0, 25, 50 and 100 uM) with
      or without pNaKtide (1 uM). MSC-derived adipocytes were evaluated for
      morphological and molecular analysis of the above markers. RESULTS: Our results
      demonstrated that 3T3-L1 cells and MSCs-derived adipocytes, treated with UTs,
      exhibited a significant decrease in adipogenesis and apoptosis through activation
      of the Na/K-ATPase/ROS amplification loop. The treatment with pNaKtide in 3T3-L1
      cells and MSC-derived adipocytes negated the effects of UTs and restored cellular
      redox in adipocytes. We noted a varying effect of pNaKtide, in adipocytes treated
      with UTs, on inflammatory markers, adipogenic marker and superoxide levels in 3T3
      L1 cells and MSC-derived adipocytes. CONCLUSIONS: This study demonstrates for the
      first time that the Na/K-ATPase/ROS amplification loop activated by elevated
      levels of UTs has varying effect on phenotypic alterations in adipocytes in
      various in vitro models. Thus, we propose that, if proven in humans, inhibition
      of Na/K-ATPase amplification of oxidant stress in CKD patients may ultimately be
      a novel way to combat adipocyte dysfunction and metabolic imbalance in these
      patients.

PMID- 30201875
TI  - Prediction Methods of Herbal Compounds in Chinese Medicinal Herbs.
AB  - Chinese herbal medicine has recently gained worldwide attention. The curative
      mechanism of Chinese herbal medicine is compared with that of western medicine at
      the molecular level. The treatment mechanism of most Chinese herbal medicines is
      still not clear. How do we integrate Chinese herbal medicine compounds with
      modern medicine? Chinese herbal medicine drug-like prediction method is
      particularly important. A growing number of Chinese herbal source compounds are
      now widely used as drug-like compound candidates. An important way for
      pharmaceutical companies to develop drugs is to discover potentially active
      compounds from related herbs in Chinese herbs. The methods for predicting the
      drug-like properties of Chinese herbal compounds include the virtual screening
      method, pharmacophore model method and machine learning method. In this paper, we
      focus on the prediction methods for the medicinal properties of Chinese herbal
      medicines. We analyze the advantages and disadvantages of the above three
      methods, and then introduce the specific steps of the virtual screening method.
      Finally, we present the prospect of the joint application of various methods.

PMID- 30201876
TI  - Preventive Effect of Flavonol Derivatives Abundant Sanglan Tea on Long-Term High
      Fat-Diet-Induced Obesity Complications in C57BL/6 Mice.
AB  - Sanglan Tea (SLT) is a Chinese medicine-based formulation that is consumed as a
      health drink for the effective management of obesity-associated complications.
      However, its chemical components and mechanism of action in the prevention of
      hepatic steatosis and obesity-related impairments have been uncertain. In this
      study, we aimed to unveil the chemical profile of SLT and to explore its
      preventive mechanism in high-fat-diet-induced non-alcoholic fatty liver disease
      (NAFLD) and obesity-related consequences in C57BL/6 mice. Ultrahigh-performance
      liquid chromatography (UHPLC) coupled to a quadrupole-orbitrap high-resolution
      mass spectrometry (MS) analysis of SLT indicated that analogs of quercetin and
      kaempferol are major compounds of flavonoids in SLT. A dietary supplement of SLT
      efficiently managed the blood glucose elevation, retained the serum total
      cholesterol (TC), LDL-cholesterol (LDL-C), and triglyceride (TG) levels, as well
      as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activity,
      and reduced the fat storage in the liver induced by a high-fat diet. The
      underlying mechanism of this preventive effect is hypothesized to be related to
      the inhibition of over-expression of lipogenesis and adipogenesis-related genes.
      Overall, this study suggests that SLT, being rich in quercetin and kaempferol
      analogs, could be a potential food supplement for the prevention of high-fat-diet
      induced NAFLD and obesity-related complications.

PMID- 30201878
TI  - The Role of Sugarcane Catalase Gene ScCAT2 in the Defense Response to Pathogen
      Challenge and Adversity Stress.
AB  - Catalases, which consist of multiple structural isoforms, catalyze the
      decomposition of hydrogen peroxide in cells to prevent membrane lipid
      peroxidation. In this study, a group II catalase gene ScCAT2 (GenBank Accession
      No. KF528830) was isolated from sugarcane genotype Yacheng05-179. ScCAT2 encoded
      a predicted protein of 493 amino acid residues, including a catalase active site
      signature (FARERIPERVVHARGAS) and a heme-ligand signature (RVFAYADTQ).
      Subcellular localization experiments showed that the ScCAT2 protein was
      distributed in the cytoplasm, plasma membrane, and nucleus of Nicotiana
      benthamiana epidermal cells. Quantitative real-time polymerase chain reaction
      (qRT-PCR) analysis indicated that the ScCAT2 gene was ubiquitously expressed in
      sugarcane tissues, with expression levels from high to low in stem skin, stem
      pith, roots, buds, and leaves. ScCAT2 mRNA expression was upregulated after
      treatment with abscisic acid (ABA), sodium chloride (NaCl), polyethylene glycol
      (PEG), and 4  degrees C low temperature, but downregulated by salicylic acid
      (SA), methyl jasmonate (MeJA), and copper chloride (CuCl2). Moreover, tolerance
      of Escherichia coli Rosetta cells carrying pET-32a-ScCAT2 was enhanced by NaCl
      stress, but not by CuCl2 stress. Sporisorium scitamineum infection of 10
      different sugarcane genotypes showed that except for YZ03-258, FN40, and FN39,
      ScCAT2 transcript abundance in four smut-resistant cultivars (Yacheng05-179, YZ01
      1413, YT96-86, and LC05-136) significantly increased at the early stage (1 day
      post-inoculation), and was decreased or did not change in the two smut-medium
      susceptibility cultivars (ROC22 and GT02-467), and one smut-susceptible cultivar
      (YZ03-103) from 0 to 3 dpi. Meanwhile, the N. benthamiana leaves that transiently
      overexpressed ScCAT2 exhibited less severe disease symptoms, more intense 3,3'
      diaminobenzidine (DAB) staining, and higher expression levels of tobacco immune
      related marker genes than the control after inoculation with tobacco pathogen
      Ralstonia solanacearum or Fusarium solani var. coeruleum. These results indicate
      that ScCAT2 plays a positive role in immune responses during plant-pathogen
      interactions, as well as in salt, drought, and cold stresses.

PMID- 30201880
TI  - Compliance to Prenatal Iron and Folic Acid Supplement Use in Relation to Low
      Birth Weight in Lilongwe, Malawi.
AB  - Prenatal iron and folic acid (IFA) supplements are offered free to all pregnant
      women in Malawi to reduce maternal anemia and improve birth outcomes. We
      investigated the association between self-reported compliance to IFA intake and
      risk of low birth weight (LBW). Pregnant women who attended Bwaila Maternity Wing
      of Lilongwe District Hospital for delivery were recruited (n = 220). We used a
      questionnaire to collect self-reported information on IFA use and maternal
      sociodemographic data. Before delivery, blood samples for maternal hemoglobin
      (Hb) and folate status, and upon delivery, birth weight, and other newborn
      anthropometrics were measured. We used multivariable logistic regression to
      determine risk of LBW by prenatal IFA intake. The self-reported number of IFA
      pills taken during pregnancy was positively associated with Hb, but not serum and
      RBC folate concentration: <45, 45-89 and >=90 pills taken corresponded with mean
      (SD) Hb 10.7 (1.6), 11.3 (1.8), and 11.7 (1.6) g/dL, respectively (p = 0.006).
      The prevalence of LBW was 20.1%, 13.5% and 5.6% for those who reported taking IFA
      pills <45, 45-89, and >=90 pills, respectively (p = 0.027). Taking >60 IFA pills
      reduced risk of LBW delivery (OR (95% CI) = 0.15 (0.03-0.70), p = 0.033) than
      taking <=30 pills. Self-reported compliance to IFA use is valid for assessing
      prenatal supplement program in Malawi, especially Hb status, and can reduce the
      rate of LBW.

PMID- 30201877
TI  - MiRNA Dysregulation in Childhood Hematological Cancer.
AB  - For decades, cancer biology focused largely on the protein-encoding genes that
      have clear roles in tumor development or progression: cell-cycle control,
      apoptotic evasion, genome instability, drug resistance, or signaling pathways
      that stimulate growth, angiogenesis, or metastasis. MicroRNAs (miRNAs), however,
      represent one of the more abundant classes of cell modulators in multicellular
      organisms and largely contribute to regulating gene expression. Many of the ~2500
      miRNAs discovered to date in humans regulate vital biological processes, and
      their aberrant expression results in pathological and malignant outcomes. In this
      review, we highlight what has been learned about the roles of miRNAs in some of
      the most common human pediatric leukemias and lymphomas, along with their value
      as diagnostic/prognostic factors.

PMID- 30201882
TI  - Synthesis of a Bone-Targeted Bortezomib with In Vivo Anti-Myeloma Effects in
      Mice.
AB  - Multiple myeloma (MM) is the most common cancer affecting the bone and bone
      marrow and remains incurable for most patients; novel therapies are therefore
      needed. Bortezomib (Btz) is an FDA-approved drug for the treatment of patients
      with MM. However, its severe side effects require a dose reduction or the
      potential discontinuation of treatment. To overcome this limitation, we
      conjugated Btz to a bisphosphonate (BP) residue lacking anti-osteoclastic
      activity using a novel chemical linker and generated a new bone-targeted Btz
      based (BP-Btz) proteasome inhibitor. We demonstrated that BP-Btz, but not Btz,
      bound to bone slices and inhibited the growth of MM cells in vitro. In a mouse
      model of MM, BP-Btz more effectively reduced tumor burden and bone loss with less
      systemic side effects than Btz. Thus, BP-Btz may represent a novel therapeutic
      approach to treat patients with MM.

PMID- 30201879
TI  - Potential Therapeutic Benefits of Herbs and Supplements in Patients with NAFLD.
AB  - Our aim is to review the efficacy of various herbs and supplements as a possible
      therapeutic option in the treatment and/or prevention of nonalcoholic fatty liver
      disease (NAFLD). We performed a systematic review of medical literature using the
      PubMed Database by searching the chemical names of many common herbs and
      supplements with "AND (NAFLD or NASH)". Studies and medical literature that
      discussed the roles and usage of herbs and supplements in NAFLD and nonalcoholic
      steatohepatitis (NASH) from inception until 20 June 2018 were reviewed. Many
      studies have claimed that the use of various herbs and supplements may improve
      disease endpoints and outcomes related to NAFLD and/or NASH. Improvement in liver
      function tests were noted. Amelioration or reduction of lobular inflammation,
      hepatic steatosis, and fibrosis were also noted. However, well-designed studies
      demonstrating improved clinical outcomes are lacking. Furthermore, experts remain
      concerned about the lack of regulation of herbs/supplements and the need for
      further research on potential adverse effects and herb-drug interactions. In
      conclusion, preliminary data on several herbs have demonstrated promising
      antioxidant, anti-inflammatory, anti-apoptotic, and anti-adipogenic properties
      that may help curtail the progression of NAFLD/NASH. Clinical trials testing the
      safety and efficacy must be completed before widespread can be recommended.

PMID- 30201883
TI  - Brain Fatty Acid Composition and Inflammation in Mice Fed with High-Carbohydrate
      Diet or High-Fat Diet.
AB  - Both high fat diet (HFD) and high carbohydrate diet (HCD) modulate brain fatty
      acids (FA) composition. Notwithstanding, there is a lack of information on time
      sequence of brain FA deposition either for HFD or HCD. The changes in brain FA
      composition in mice fed with HFD or HCD for 7, 14, 28, or 56 days were compared
      with results of 0 (before starting given the diets). mRNA expressions of
      allograft inflammatory factor 1 (Aif1), cyclooxygenase-2 (Cox 2), F4/80,
      inducible nitric oxide synthase (iNOS), integrin subunit alpha m (Itgam),
      interleukin IL-1beta (IL-1beta), IL-6, IL-10, and tumor necrosis factor alpha
      (TNF-alpha) were measured. The HFD group had higher speed of deposition of
      saturated FA (SFA), monounsaturated FA (MUFA), and polyunsaturated FA (PUFA) at
      the beginning of the experimental period. However, on day 56, the total amount of
      SFA, MUFA, and PUFA were similar. mRNA expressions of F4/80 and Itgam, markers of
      microglia infiltration, were increased (p < 0.05) in the brain of the HCD group
      whereas inflammatory marker index (IMI) was higher (46%) in HFD group. In
      conclusion, the proportion of fat and carbohydrates in the diet modulates the
      speed deposition of FA and expression of inflammatory gene markers.

PMID- 30201885
TI  - An LC Passive Wireless Gas Sensor Based on PANI/CNT Composite.
AB  - This paper proposes a wireless passive gas sensor based on the principle of LC
      mutual coupling. After the acidification of the carbon nanotube (CNT), the in
      situ polymerization of the aminobenzene monomers was conducted on the surface of
      the acidified CNT to form a sensitive material composed of a polyaniline/carbon
      nanotube (PANI/CNT) composite. The Advanced Design System (ADS) software was used
      for simulating and analyzing the designed structure, which obtained the various
      parameters of the structure. A lead-free aluminum paste was printed on an alumina
      ceramic substrate via the screen printing technique to form an inductor coil,
      before the gas sensitive material was applied to prepare a wireless passive gas
      sensor, consisting of a single-turn inductor and interdigitated electrodes on the
      base structure. Finally, an experimental platform was built to test the
      performance of the sensor. The sensitivity of the gas sensor is about 0.04
      MHz/ppm in an atmosphere with a NH3 concentration of 300 ppm. The sensor was
      shown to have good repeatability and high stability over a long time period.

PMID- 30201881
TI  - The Biology of Glial Cells and Their Complex Roles in Alzheimer's Disease: New
      Opportunities in Therapy.
AB  - Even though Alzheimer's disease (AD) is of significant interest to the scientific
      community, its pathogenesis is very complicated and not well-understood. A great
      deal of progress has been made in AD research recently and with the advent of
      these new insights more therapeutic benefits may be identified that could help
      patients around the world. Much of the research in AD thus far has been very
      neuron-oriented; however, recent studies suggest that glial cells, i.e.,
      microglia, astrocytes, oligodendrocytes, and oligodendrocyte progenitor cells
      (NG2 glia), are linked to the pathogenesis of AD and may offer several potential
      therapeutic targets against AD. In addition to a number of other functions, glial
      cells are responsible for maintaining homeostasis (i.e., concentration of ions,
      neurotransmitters, etc.) within the central nervous system (CNS) and are crucial
      to the structural integrity of neurons. This review explores the: (i) role of
      glial cells in AD pathogenesis; (ii) complex functionalities of the components
      involved; and (iii) potential therapeutic targets that could eventually lead to a
      better quality of life for AD patients.

PMID- 30201886
TI  - 3D Measurement Simulation and Relative Pointing Error Verification of the
      Telescope Mount Assembly Subsystem for the Large Synoptic Survey Telescope.
AB  - An engineering validation of a large optical telescope consists of executing
      major performing tests at the subsystem level to verify the overall engineering
      performance of the observatory. Thus, the relative pointing error verification of
      the telescope mount assembly subsystem is of special interest to guarantee the
      absolute pointing performance of the large synoptic survey telescope. This paper
      presents a new verification method for the relative pointing error assessment of
      the telescope mount assembly, based on laser tracker technology and several
      fiducial points fixed to the floor. Monte-Carlo-based simulation results show
      that the presented methodology is fit for purpose, even if floor movement occurs
      due to temperature variation during the measurement acquisition process. A
      further research about laser tracker technology integration into the telescope
      structure may suggest that such laser tracker technology could be permanently
      installed in the telescope in order to provide an active alignment system that
      aims to detect and correct possible misalignment between mirrors or to provide
      the required mirror positioning verification accuracy after maintenance
      activities. The obtained results show that two on-board laser tracker systems
      combined with eight measurement targets could result in measurement uncertainties
      that are better than 1 arcsec, which would provide a reliable built-in metrology
      tool for large telescopes.

PMID- 30201884
TI  - Genome-Wide DNA Methylation Comparison between Brassica napus Genic Male Sterile
      Line and Restorer Line.
AB  - DNA methylation is an essential epigenetic modification that dynamically
      regulates gene expression during plant development. However, few studies have
      determined the DNA methylation profiles of male-sterile rapeseed. Here, we
      conducted a global comparison of DNA methylation patterns between the rapeseed
      genic male sterile line 7365A and its near-isogenic fertile line 7365B by whole
      genome bisulfite sequencing (WGBS). Profiling of the genome-wide DNA methylation
      showed that the methylation level in floral buds was lower than that in leaves
      and roots. Besides, a total of 410 differentially methylated region-associated
      genes (DMGs) were identified in 7365A relative to 7365B. Traditional bisulfite
      sequencing polymerase chain reaction (PCR) was performed to validate the WGBS
      data. Eleven DMGs were found to be involved in anther and pollen development,
      which were analyzed by quantitative PCR. In particular, Bnams4 was hypo
      methylated in 7365A, and its expression was up-regulated, which might affect
      other DMGs and thus control the male sterility. This study provided genome-wide
      DNA methylation profiles of floral buds and important clues for revealing the
      molecular mechanism of genic male sterility in rapeseed.

PMID- 30201888
TI  - New Coordination Complexes Based on the 2,6-bis[1-(Phenylimino)ethyl] Pyridine
      Ligand: Effective Catalysts for the Synthesis of Propylene Carbonates from Carbon
      Dioxide and Epoxides.
AB  - We aimed to develop new effective catalysts for the synthesis of propylene
      carbonate from propylene oxide and carbon dioxide. A kind of Mx+LClx coordination
      complex was fabricated based on the chelating tridentate ligand 2,6-bis[1
      (phenylimino)ethyl] pyridine (L). The obtained products were characterized by
      elemental analysis, infrared spectroscopy, ultraviolet spectroscopy,
      thermogravimetric analysis, and single-crystal X-ray diffraction. It was found
      that the catalytic activity of the complexes with different metal ions, the same
      ligand differed and co-catalyst, where the order of greatest to least catalytic
      activity was 2 > 3 > 1. The catalytic system composed of complex 2 and DMAP
      proved to have the better catalytic performance. The yields for complex 2 systems
      was 86.7% under the reaction conditions of 100  degrees C, 2.5 MPa, and 4 h. The
      TOF was 1026 h-1 under the reaction conditions of 200  degrees C, 2.5 MPa, and 1
      h. We also explored the influence of time, pressure, temperature, and reaction
      substrate concentration on the catalytic reactions. A hypothetical catalytic
      reaction mechanism is proposed based on density functional theory (DFT)
      calculations and the catalytic reaction results.

PMID- 30201887
TI  - Hypertension Assessment via ECG and PPG Signals: An Evaluation Using MIMIC
      Database.
AB  - Cardiovascular diseases (CVDs) have become the biggest threat to human health,
      and they are accelerated by hypertension. The best way to avoid the many
      complications of CVDs is to manage and prevent hypertension at an early stage.
      However, there are no symptoms at all for most types of hypertension, especially
      for prehypertension. The awareness and control rates of hypertension are
      extremely low. In this study, a novel hypertension management method based on
      arterial wave propagation theory and photoplethysmography (PPG) morphological
      theory was researched to explore the physiological changes in different blood
      pressure (BP) levels. Pulse Arrival Time (PAT) and photoplethysmogram (PPG)
      features were extracted from electrocardiogram (ECG) and PPG signals to represent
      the arterial wave propagation theory and PPG morphological theory, respectively.
      Three feature sets, one containing PAT only, one containing PPG features only,
      and one containing both PAT and PPG features, were used to classify the different
      BP categories, defined as normotension, prehypertension, and hypertension. PPG
      features were shown to classify BP categories more accurately than PAT.
      Furthermore, PAT and PPG combined features improved the BP classification
      performance. The F1 scores to classify normotension versus prehypertension
      reached 84.34%, the scores for normotension versus hypertension reached 94.84%,
      and the scores for normotension plus prehypertension versus hypertension reached
      88.49%. This indicates that the simultaneous collection of ECG and PPG signals
      could detect hypertension.

PMID- 30201890
TI  - InPBi Quantum Dots for Super-Luminescence Diodes.
AB  - InPBi thin film has shown ultra-broad room temperature photoluminescence, which
      is promising for applications in super-luminescent diodes (SLDs) but met problems
      with low light emission efficiency. In this paper, InPBi quantum dot (QD) is
      proposed to serve as the active material for future InPBi SLDs. The quantum
      confinement for carriers and reduced spatial size of QD structure can improve
      light emission efficiently. We employ finite element method to simulate strain
      distribution inside QDs and use the result as input for calculating electronic
      properties. We systematically investigate different transitions involving
      carriers on the band edges and the deep levels as a function of Bi composition
      and InPBi QD geometry embedded in InAlAs lattice matched to InP. A flat QD shape
      with a moderate Bi content of a few percent over 3.2% would provide the optimal
      performance of SLDs with a bright and wide spectrum at a short center wavelength,
      promising for future optical coherence tomography applications.

PMID- 30201889
TI  - Magnetic Targeting of Growth Factors Using Iron Oxide Nanoparticles.
AB  - Growth factors play an important role in nerve regeneration and repair. An
      attractive drug delivery strategy, termed "magnetic targeting", aims to enhance
      therapeutic efficiency by directing magnetic drug carriers specifically to
      selected cell populations that are suitable for the nervous tissues. Here, we
      covalently conjugated nerve growth factor to iron oxide nanoparticles (NGF-MNPs)
      and used controlled magnetic fields to deliver the NGF-MNP complexes to target
      sites. In order to actuate the magnetic fields a modular magnetic device was
      designed and fabricated. PC12 cells that were plated homogenously in culture were
      differentiated selectively only in targeted sites out of the entire dish,
      restricted to areas above the magnetic "hot spots". To examine the ability to
      guide the NGF-MNPs towards specific targets in vivo, we examined two model
      systems. First, we injected and directed magnetic carriers within the sciatic
      nerve. Second, we injected the MNPs intravenously and showed a significant
      accumulation of MNPs in mouse retina while using an external magnet that was
      placed next to one of the eyes. We propose a novel approach to deliver drugs
      selectively to injured sites, thus, to promote an effective repair with minimal
      systemic side effects, overcoming current challenges in regenerative
      therapeutics.

PMID- 30201891
TI  - Role of Cannabinoids in Obesity.
AB  - Obesity is an increasing health problem worldwide. Its related comorbidities
      imply a high cost for the National Health System and diminish a patient's life
      quality. Adipose tissue is composed of three types of cells. White adipocytes are
      involved in fat storage and secretion of hormones. Brown adipocytes are involved
      in thermogenesis and caloric expenditure. Beige adipocytes are transitional
      adipocytes that in response to various stimuli can turn from white to brown and
      could be protective against the obesity, enhancing energy expenditure. The
      conversion of white in beige adipose tissue is a potential new therapeutic target
      for obesity. Cannabinoid receptors (CB) regulate thermogenesis, food intake and
      inflammation. CB1 ablation or inhibition helps reducing body weight and food
      intake. Stimulation of CB2 limits inflammation and promotes anti-obesity effects
      by reducing food intake and weight gain. Its genetic ablation results in
      adiposity development. CB receptors are also responsible for transforming white
      adipose tissue towards beige or brown adipocytes, therefore their modulation can
      be considered potential anti-obesity target. CB1 principal localization in
      central nervous system represents an important limit. Stimulation of CB2,
      principally localized on peripheral cells instead, should facilitate the anti
      obesity effects without exerting remarkable psychotropic activity.

PMID- 30201892
TI  - Fractional-Order PID Control Strategy on Hydraulic-Loading System of Typical
      Electromechanical Platform.
AB  - In this paper, a control method for a hydraulic loading system of an
      electromechanical platform based on a fractional-order PID (Proportion
      Integration-Differentiation) controller is proposed, which is used to drive the
      loading system of a mechatronic journal test rig. The mathematical model of the
      control system is established according to the principle of the electro-hydraulic
      system. Considering the indetermination of model parameters, the method of
      parameter identification was used to verify the rationality of the theoretical
      model. In order to improve the control precision of the hydraulic loading system,
      the traditional PID controller and fractional-order PID controller are designed
      by selecting appropriate tuning parameters. Their control performances are
      analyzed in frequency domain and time domain, respectively. The results show that
      the fractional-order PID controller has better control effect. By observing the
      actual control effect of the fractional-order PID controller on the journal test
      rig, the effectiveness of this control algorithm is verified.

PMID- 30201893
TI  - Phenethyl Isothiocyanate Inhibits In Vivo Growth of Xenograft Tumors of Human
      Glioblastoma Cells.
AB  - Phenethyl isothiocyanate (PEITC) from cruciferous vegetables can inhibit the
      growth of various human cancer cells. In previous studies, we determined that
      PEITC inhibited the in vitro growth of human glioblastoma GBM 8401 cells by
      inducing apoptosis, inhibiting migration and invasion, and altering gene
      expression. Nevertheless, there are no further in vivo reports disclosing whether
      PEITC can suppress the growth of glioblastoma. Therefore, in this study we
      investigate the anti-tumor effects of PEITC in a xenograft model of glioblastoma
      in nude mice. Thirty nude mice were inoculated subcutaneously with GBM 8401
      cells. Mice with one palpable tumor were divided randomly into three groups:
      control, PEITC-10, and PEITC-20 groups treated with 0.1% dimethyl sulfoxide
      (DMSO), and 10 and 20 MUmole PEITC/100 MUL PBS daily by oral gavage,
      respectively. PEITC significantly decreased tumor weights and volumes of GBM 8401
      cells in mice, but did not affect the total body weights of mice. PEITC
      diminished the levels of anti-apoptotic proteins MCL-1 (myeloid cell leukemia 1)
      and XIAP (X-linked inhibitor of apoptosis protein) in GBM 8401 cells. PEITC
      enhanced the levels of caspase-3 and Bax in GBM 8401 cells. The growth of
      glioblastoma can be suppressed by the biological properties of PEITC in vivo.
      These effects might support further investigations into the potential use of
      PEITC as an anticancer drug for glioblastoma.

PMID- 30201894
TI  - The NOAEL Metformin Dose Is Ineffective against Metabolic Disruption Induced by
      Chronic Cadmium Exposure in Wistar Rats.
AB  - Previous studies have proposed that cadmium (Cd) is a metabolic disruptor, which
      is associated with insulin resistance, metabolic syndrome, and diabetes. This
      metal is not considered by international agencies for the study of metabolic
      diseases. In this study, we investigate the effect of metformin on Cd-exposed
      Wistar rats at a lowest-observed-adverse-effect level (LOAEL) dose (32.5 ppm) in
      drinking water. Metabolic complications in the rats exposed to Cd were
      dysglycemia, insulin resistance, dyslipidemia, dyslipoproteinemia, and imbalance
      in triglyceride and glycogen storage in the liver, muscle, heart, kidney, and
      adipose tissue. Meanwhile, rats treated orally with a No-observable-adverse
      effect level (NOAEL) dose of metformin (200 mg/kg/day) showed mild improvement on
      serum lipids, but not on glucose tolerance; in tissues, glycogen storage was
      improved, but lipid storage was ineffective. In conclusion, metformin as a first
      line pharmacological therapy must take into consideration the origin and duration
      of metabolic disruption, because in this work the NOAEL dose of metformin (200
      mg/kg/day) showed a limited efficiency in the metabolic disruption caused by
      chronic Cd exposure.

PMID- 30201895
TI  - Fucoxanthin Inhibits Myofibroblast Differentiation and Extracellular Matrix
      Production in Nasal Polyp-Derived Fibroblasts via Modulation of Smad-Dependent
      and Smad-Independent Signaling Pathways.
AB  - Nasal polyps (NPs) are a multifactorial disorder associated with a chronic
      inflammatory state of the nasal mucosa. Fucoxanthin (Fx) is a characteristic
      orange carotenoid obtained from brown algae and has diverse immunological
      properties. The present study investigated whether Fx inhibits fibrosis-related
      effects in nasal polyp-derived fibroblasts (NPDFs) and elucidated the molecular
      signaling pathways involved. The production of collagen type I (Col-1) was
      investigated in NP tissue via immunohistochemistry and western blot analysis.
      NPDFs were treated with transforming growth factor (TGF)-beta1 (1 ng/mL) in the
      presence or absence of Fx (5-30 uM). The levels of alpha-smooth muscle actin
      (alpha-SMA), Col-1, and phosphorylated (p)-Smad 2/3, signal protein-1 (SP-1),
      MAPKs (mitogen-activated protein kinases), and Akt were measured by western blot
      analysis. The expression of Col-1 was detected in NP tissues. TGF-beta1
      stimulated the production of alpha-SMA and Col-1, and stimulated the contraction
      of collagen gel. However, pretreatment with Fx attenuated these effects.
      Furthermore, these inhibitory effects were mediated through modulation of both
      Smad 2/3 and Akt/SP-1 signaling pathways in TGF-beta1-induced NPDFs. The results
      from the present study suggest that Fx may be a novel anti-fibrotic agent for the
      treatment of NP formation.

PMID- 30201896
TI  - Health Impacts of Exposure to Gaseous Pollutants and Particulate Matter in
      Beijing-A Non-Linear Analysis Based on the New Evidence.
AB  - This paper aimed to estimate health risks focusing on respiratory diseases from
      exposure to gaseous multi-pollutants based on new data and revealed new evidence
      after the most stringent air pollution control plan in Beijing which was carried
      out in 2013. It used daily respiratory diseases outpatient data from a hospital
      located in Beijing with daily meteorological data and monitor data of air
      pollutants from local authorities. All data were collected from 2014 to 2016.
      Distributed lag non-linear model was employed. Results indicated that NO2 and CO
      had positive association with outpatients number on the day of the exposure
      (1.045 (95% confidence interval (CI): 1.003, 1.089) for CO and 1.022 (95% CI:
      1.008, 1.036) for NO2) (and on the day after the exposure (1.026 (95% CI: 1.005,
      1.048) for CO and 1.013 (95% CI: 1.005, 1.021) for NO2). Relative risk (RR)
      generally declines with the number of lags; ozone produces significant effects on
      the first day (RR = 0.993 (95% CI: 0.989, 0.998)) as well as second day (RR =
      0.995 (95% CI: 0.991, 0.999)) after the exposure, while particulate pollutants
      did not produce significant effects. Effects from the short-term exposure to
      gaseous pollutants were robust after controlling for particulate matters. Our
      results contribute to a comprehensive understanding of the dependencies between
      the change of air pollutants concentration and their health effects in Beijing
      after the implementation of promising air regulations in 2013. Results of the
      study can be used to develop relevant measures minimizing the adverse health
      consequences of air pollutants and supporting sustainable development of Beijing
      as well as other rapidly growing Asian cities.

PMID- 30201897
TI  - Comparative In Vitro and In Silico Analysis of the Selectivity of Indirubin as a
      Human Ah Receptor Agonist.
AB  - The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor
      that modulates gene expression following its binding and activation by
      structurally diverse chemicals. Species differences in AhR functionality have
      been observed, with the mouse AhR (mAhR) and human AhR (hAhR) exhibiting
      significant differences in ligand binding, coactivator recruitment, gene
      expression and response. While the AhR agonist indirubin (IR) is a more potent
      activator of hAhR-dependent gene expression than the prototypical ligand 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD), it is a significantly less potent activator
      of the mAhR. DNA binding analysis confirmed the greater potency/efficacy of IR in
      stimulating transformation/DNA binding of the hAhR in vitro and domain-swapping
      experiments demonstrated that the enhanced response to IR was primarily due to
      the hAhR ligand binding domain (LBD). Site-directed mutagenesis and functional
      analysis studies revealed that mutation of H326 and A349 in the mAhR LBD to the
      corresponding residues in the hAhR LBD significantly increased the potency of IR.
      Since these mutations had no significant effect on ligand binding, these residues
      likely contribute to an enhanced efficiency of transformation/DNA binding by IR
      bound hAhR. Molecular docking to mAhR LBD homology models further elucidated the
      different roles of the A375V mutation in TCDD and IR binding, as revealed by
      [3H]TCDD competitive binding results. These results demonstrate the differential
      binding of structurally diverse ligands within the LBD of a given AhR and confirm
      that amino acid differences within the LBD of AhRs contribute to significant
      species differences in ligand response.

PMID- 30201898
TI  - Chemical Sensing Employing Plant Electrical Signal Response-Classification of
      Stimuli Using Curve Fitting Coefficients as Features.
AB  - In order to exploit plants as environmental biosensors, previous researches have
      been focused on the electrical signal response of the plants to different
      environmental stimuli. One of the important outcomes of those researches has been
      the extraction of meaningful features from the electrical signals and the use of
      such features for the classification of the stimuli which affected the plants.
      The classification results are dependent on the classifier algorithm used,
      features extracted and the quality of data. This paper presents an innovative way
      of extracting features from raw plant electrical signal response to classify the
      external stimuli which caused the plant to produce such a signal. A curve fitting
      approach in extracting features from the raw signal for classification of the
      applied stimuli has been adopted in this work, thereby evaluating whether the
      shape of the raw signal is dependent on the stimuli applied. Four types of curve
      fitting models-Polynomial, Gaussian, Fourier and Exponential, have been explored.
      The fitting accuracy (i.e., fitting of curve to the actual raw signal) depicted
      through R-squared values has allowed exploration of which curve fitting model
      performs best. The coefficients of the curve fit models were then used as
      features. Thereafter, using simple classification algorithms such as Linear
      Discriminant Analysis (LDA), Quadratic Discriminant Analysis (QDA) etc. within
      the curve fit coefficient space, we have verified that within the available data,
      above 90% classification accuracy can be achieved. The successful hypothesis
      taken in this work will allow further research in implementing plants as
      environmental biosensors.

PMID- 30201899
TI  - Liposomal Form of the Echinochrome-Carrageenan Complex.
AB  - Inclusion of drugs in liposomes offers the potential for localized and sustained
      delivery to mucosal surfaces. The inclusion of the carrageenan matrix with
      echinochrome A ((Ech)-the active substance of the drug Histochrome) in liposomes
      was studied. According to the spectral characteristics, Ech was not oxidized and
      retained stability after encapsulation in the liposomes and the lyophilization
      process. Loading the liposomes with negatively charged polysaccharide results in
      the increase in the zeta potential to more negative values (from -14.6 to -24.4
      mV), that together with an increasing in the sizes of liposomes (from 125.6 +/-
      2.5 nm to 159.3 +/- 5.8 nm) propose of the formation of the polymer coating on
      liposomes. The interactions of liposomes with porcine stomach mucin was
      determined by the DLS and SEM methods. The changes in the zeta-potential and size
      of the mucin particles were observed as the result of the interaction of
      liposomes with mucin. To evaluate the mucoadhesive properties of liposomes and
      the penetration of Ech in the mucosa, a fresh-frozen inner surface of the small
      intestine of a pig as a model of mucous tissue was used. Polysaccharide-coated
      liposomes exhibit very good mucoadhesive properties -50% of Ech remains on the
      mucosa.

PMID- 30201900
TI  - Assessment of Bacterial Accumulation and Environmental Factors in Sentinel
      Oysters and Estuarine Water Quality from the Phang Nga Estuary Area in Thailand.
AB  - This study characterized microbiological and chemical contamination of oyster
      meat and estuarine water in Phang Nga, Thailand. Pooled oyster meats (n = 144),
      estuarine waters (n = 96) and environmental parameters were collected from March,
      2016 to February, 2017, and assessed for levels of total coliforms (TC), fecal
      coliforms (FC), Escherichia coli (EC), and Vibrio parahaemolyticus (VP), presence
      of Salmonella and Shigella and levels of heavy metals (Mn, Pb and Cd). The
      prevalence of TC, FC and EC were in 99.3%, 94.4% and 93.1% of oyster meat and
      94.8%, 79.2%, and 78.1% of water, respectively. The average VP levels was 8.5 *
      107 most probable number (MPN)/g oyster. Prevalence of Shigella and Salmonella in
      the pooled oysters were 7.6% and 30.6%, respectively. The dominant Salmonella
      serovars were Paratyphi B followed by Seremban, and Kentucky. In contrast, the
      prevalence of Shigella were 27.1%, but Salmonella was not detected in estuarine
      water. Factors statistically associated with EC accumulation in oyster were level
      of FC, 7-day average precipitation, temperature, relative humidity, and presence
      of Salmonella in the sample. The optimal cutoff value of EC to predict Salmonella
      in oyster was 420 MPN/g. Results indicate this area has relatively safe levels of
      heavy metals, whereas bacterial contamination was very high for oysters.

PMID- 30201902
TI  - A Sparse-Based Off-Grid DOA Estimation Method for Coprime Arrays.
AB  - Recently, many sparse-based direction-of-arrival (DOA) estimation methods for
      coprime arrays have become popular for their excellent detection performance.
      However, these methods often suffer from grid mismatch problem due to the
      discretization of the potential angle space, which will cause DOA estimation
      performance degradation when the target is off-grid. To this end, we proposed a
      sparse-based off-grid DOA estimation method for coprime arrays in this paper,
      which includes two parts: coarse estimation process and fine estimation process.
      In the coarse estimation process, the grid points closest to the true DOAs, named
      coarse DOAs, are derived by solving an optimization problem, which is constructed
      according to the statistical property of the vectorized covariance matrix
      estimation error. Meanwhile, we eliminate the unknown noise variance effectively
      through a linear transformation. Due to finite snapshots effect, some undesirable
      correlation terms between signal and noise vectors exist in the sample covariance
      matrix. In the fine estimation process, we therefore remove the undesirable
      correlation terms from the sample covariance matrix first, and then utilize a two
      step iterative method to update the grid biases. Combining the coarse DOAs with
      the grid biases, the final DOAs can be obtained. In the end, simulation results
      verify the effectiveness of the proposed method.

PMID- 30201901
TI  - The Possibility of Applying the Vitamin D Brief Food Frequency Questionnaire as a
      Tool for a Country with No Vitamin D Data in Food Composition Tables.
AB  - Although the role of vitamin D is well known, the possibility of assessing its
      intake may be constricted in countries with no vitamin D data in food composition
      tables, as in the case of Croatia. The aim of the presented study was to adjust
      the VIDEO-FFQ (Vitamin D Estimation Only-Food Frequency Questionnaire),
      previously validated in Poland, to the Croatian population and to assess the
      validity and reproducibility of the adjusted Cro-VIDEO-FFQ (Croatian-VIDEO-FFQ).
      The study involved a group of Croatian women aged 20-30 and the Polish
      questionnaire was adjusted for a population due to similarities of the
      nutritional habits between countries. 106 individuals were recruited and 63
      completed all the stages of the study. Participants conducted a 3-day dietary
      record and filled out the Cro-VIDEO-FFQ1 (first stage), as well as the same
      questionnaire (Cro-VIDEO-FFQ2) 6 weeks after (second stage). The following
      vitamin D intakes were observed in the studied group: 1.9 ug (0.2-8.0 ug) for 3
      day dietary record, 3.3 ug (1.1-10.6 ug) for Cro-VIDEO-FFQ1, 3.6 ug (1.4-7.8 ug)
      for Cro-VIDEO-FFQ2. The Bland-Altman indexes in assessment of validity and
      reproducibility were 4.8% and 6.3%, respectively, with mean differences of 0.55
      ug and 0.12 ug, as well as limits of agreement -0.91-2.01 ug and -0.44-0.69 ug.
      The kappa coefficient indicated a fair agreement for validity (0.21) and
      substantial for reproducibility (0.62), while correlations were significant (p =
      0.0027, r = 0.37 for validity; p < 0.0001, r = 0.80 for reproducibility). It was
      observed that VIDEO-FFQ may be adjusted as a simple tool to assess vitamin D
      intake in a population with no vitamin D data in food composition tables, while
      Cro-VIDEO-FFQ may be a valid tool for nutritional assessment in Croatia.

PMID- 30201903
TI  - Melatonin Inhibits the Progression of Hepatocellular Carcinoma through MicroRNA
      Let7i-3p Mediated RAF1 Reduction.
AB  - Melatonin is the main pineal hormone that relays light/dark-cycle information to
      the circadian system. Recent studies have examined the intrinsic antitumor
      activity of melatonin in various cancers, including hepatocellular carcinoma
      (HCC), the primary life-threatening malignancy in both sexes in Taiwan. However,
      the detailed regulatory mechanisms underlying melatonin's anti-HCC activity
      remain incompletely understood. Here, we investigated the mechanisms by which the
      anti-HCC activity of melatonin is regulated. Human hepatoma cell lines were
      treated with 1 and 2 mM melatonin, and functional assays were used to dissect
      melatonin's antitumor effect in HCC; small-RNA sequencing was performed to
      identify the microRNAs (miRNAs) involved in the anti-HCC activity of melatonin;
      and quantitative RT-PCR and Western blotting were used to elucidate how miRNAs
      regulate melatonin-mediated HCC suppression. Melatonin treatment at both doses
      strongly inhibited the proliferation, migration and invasion capacities of Huh7
      and HepG2 cell lines, and melatonin treatment markedly induced the expression of
      the miRNA let7i-3p in cells. Notably, transfection of cells with a let7i-3p mimic
      drastically reduced RAF1 expression and activation of mitogen-activated protein
      kinase signaling downstream from RAF1, and rescue-assay results demonstrated that
      melatonin inhibited HCC progression by modulating let7i-3p-mediated RAF1
      suppression. Our findings support the view that melatonin treatment holds
      considerable promise as a therapy for HCC.

PMID- 30201904
TI  - Association between Cognitive Restraint, Uncontrolled Eating, Emotional Eating
      and BMI and the Amount of Food Wasted in Early Adolescent Girls.
AB  - Understanding of behavioral factors associated with obesity is of importance in
      addressing this issue. This study examined the association between cognitive
      restraint, uncontrolled eating, emotional eating and body mass index (BMI) and
      amount of food plated, consumed, leftovers, and leftover food thrown into the
      trash (food wasted) in early adolescent girls nine to 13 years in O'ahu, Hawai'i
      (n = 93). Food plated, consumed, leftovers, and food wasted were estimated using
      a three-day mobile food recordTM (mFR). Weight and height were measured to
      compute BMI (kg/m2). The three-factor eating questionnaire provided a score from
      0 to 100 for cognitive restraint, uncontrolled eating, and emotional eating.
      Higher scores are indicative of greater cognitive restraint, uncontrolled eating,
      and emotional eating. Pearson's correlations were computed to examine the
      relationship between three factor eating scores and BMI. General linear models
      were conducted to examine the effect of each of three-factor eating scores on
      food plated, consumed, leftovers, and food wasted. Cognitive restraint was
      positively correlated with BMI (r = 0.36, p < 0.001) and with BMI z-score (r =
      0.40, p < 0.001). There were no associations between three-factor eating scores
      and food plated, consumed, leftovers, and food wasted at lunch. However, at
      dinner, total energy plated, left over, and food wasted increased by 4.24
      kcal/day (p = 0.030), 1.67 kcal/day (p = 0.002), and 0.93 kcal/day (p = 0.031),
      respectively, with a unit increase in uncontrolled eating score. Similarly, total
      energy plated and energy left over at dinner increased by 3.40 kcal/day (p =
      0.045) and 1.51 kcal/day (p = 0.001), respectively, with a unit increase in
      emotional eating score. Additional research should examine the specific roles of
      cognitive restraint, uncontrolled eating, emotional eating and food waste in the
      development of obesity in adolescents.

PMID- 30201906
TI  - Effects of Angular Dependency of Particulate Light Scattering Intensity on
      Determination of Samples with Bimodal Size Distributions Using Dynamic Light
      Scattering Methods.
AB  - The angular dependency of light scattering intensity from differently sized
      particles strongly influences the apparent particle size distribution, as
      determined by dynamic light scattering (DLS) methods. Manufactured nanomaterials
      have size distributions more or less; therefore, the effect of detecting the
      angular dependency of the apparent size distribution by DLS is crucial.
      Commercial DLS instruments typically have two different types of detector angular
      position. The first is a detector angled at 90 degrees , and the other is a
      backscattering angle detector. We therefore investigated the coverage and angular
      dependency when determining the relative concentrations of nanoparticles in
      polystyrene latex samples with a bimodal size distribution, using DLS methods
      both experimentally and theoretically. We used five differently sized polystyrene
      latex particles (one was a 70-nm nanoparticle and the others were various
      submicron-sized particles) in a variety of mixtures (the ratio of the difference
      of particle sizes ranged from approximately 2 to 7) to investigate the coverage
      and angular dependency of the recognition of the relative concentration ratio. In
      the case of size difference of approximately a factor of 2 or 3 between the two
      mixed particles (one was fixed at 70 nm), for DLS measurements at light
      scattering detector angles ranging from 60 degrees  to 150 degrees , the homodyne
      photon correlation functions were approximately straight lines for mixtures of
      two differently sized polystyrene latex particles. The straight homodyne photon
      correlation functions were caused by the relatively strong light scattering from
      larger submicron particles masking the weaker light scattering from the smaller
      nanoparticles. As a result, DLS analysis could not recognize the relative
      concentration of nanoparticles in the mixture. In contrast to these samples, for
      mixtures of two differently sized polystyrene latex particles (one was 70 nm in
      size) with a size difference of a factor of 5, the homodyne correlation functions
      displayed an obvious curve for angles larger than 120 degrees . This curve
      reflected an appropriate relative concentration ratio for the two differently
      sized polystyrene latex particles. Furthermore, for a mixture of two differently
      sized particles (one was again 70 nm) with size differences of a factor of 7, the
      homodyne correlation functions showed a clearly curved shape for detector angles
      larger than 90 degrees , and yielded appropriate relative concentration ratios
      for the two different sizes of polystyrene latex particles. These observations
      were supported by theoretical investigation using Mie theory and asymmetric flow
      field-flow fractionation measurements with a multi-angle light scattering
      detector. Our investigation is crucial for achieving some degree of concordance
      on the determination of the size distribution of particles using DLS methods in
      industrial and academic fields.

PMID- 30201905
TI  - Feeding the Walls: How Does Nutrient Availability Regulate Cell Wall Composition?
AB  - Nutrients are critical for plants to grow and develop, and nutrient depletion
      severely affects crop yield. In order to optimize nutrient acquisition, plants
      adapt their growth and root architecture. Changes in growth are determined by
      modifications in the cell walls surrounding every plant cell. The plant cell
      wall, which is largely composed of complex polysaccharides, is essential for
      plants to attain their shape and to protect cells against the environment. Within
      the cell wall, cellulose strands form microfibrils that act as a framework for
      other wall components, including hemicelluloses, pectins, proteins, and, in some
      cases, callose, lignin, and suberin. Cell wall composition varies, depending on
      cell and tissue type. It is governed by synthesis, deposition and remodeling of
      wall components, and determines the physical and structural properties of the
      cell wall. How nutrient status affects cell wall synthesis and organization, and
      thus plant growth and morphology, remains poorly understood. In this review, we
      aim to summarize and synthesize research on the adaptation of root cell walls in
      response to nutrient availability and the potential role of cell walls in
      nutrient sensing.

PMID- 30201907
TI  - Iron Absorption in Iron-Deficient Women, Who Received 65 mg Fe with an Indonesian
      Breakfast, Is Much Better from NaFe(III)EDTA than from Fe(II)SO4, with an
      Acceptable Increase of Plasma NTBI. A Randomized Clinical Trial.
AB  - Plasma non-transferrin-bound iron (NTBI) is potentially harmful due to the
      generation of free radicals that cause tissue damage in vascular and other
      diseases. Studies in iron-replete and iron-deficient subjects, receiving a single
      oral test dose of Fe(II)SO4 or NaFe(III)EDTA with water, revealed that FeSO4 was
      well absorbed when compared with NaFeEDTA, while only the Fe(II) compound showed
      a remarkable increase of NTBI. As NaFeEDTA is successfully used for food
      fortification, a double-blind randomized cross-over trial was conducted in 11
      healthy women with uncomplicated iron deficiency. All subjects received a
      placebo, 6.5 mg FeSO4, 65 mg FeSO4, 6.5 mg NaFeEDTA, and 65 mg NaFeEDTA with a
      traditional Indonesian breakfast in one-week intervals. Blood tests were carried
      out every 60 min for five hours. NTBI detection was performed using the
      fluorescein-labeled apotransferrin method. Plasma iron values were highly
      increased after 65 mg NaFeEDTA, twice as high as after FeSO4. A similar pattern
      was seen for NTBI. After 6.5 mg of NaFeEDTA and FeSO4, NTBI was hardly
      detectable. NaFeEDTA was highly effective for the treatment of iron deficiency if
      given with a meal, inhibiting the formation of nonabsorbable Fe-complexes, while
      NTBI did not exceed the range of normal values for iron-replete subjects.

PMID- 30201908
TI  - Tetrahydroxystilbene Glucoside Regulates Proliferation, Differentiation, and
      OPG/RANKL/M-CSF Expression in MC3T3-E1 Cells via the PI3K/Akt Pathway.
AB  - Tetrahydroxystilbene glucoside (TSG) is a unique component of the bone
      reinforcing herb Radix Polygoni Multiflori Preparata (RPMP). It has the ability
      to promote bone formation and protect osteoblasts. However, the underlying
      mechanism remains unclear. To better understand its biological function, we
      determined TSG's effect on murine pre-osteoblastic MC3T3-E1 cells by the MTT
      assay, flow cytometry, FQ-PCR, Western blot, and ELISA. The results showed that
      TSG caused an elevation of the MC3T3-E1 cell number, the number of cells in the S
      phase, and the mRNA levels of the runt-related transcription factor-2 (Runx2),
      osterix (Osx), and collagen type I alpha1 (Col1a1). In addition, the
      osteoprotegerin (OPG) mRNA level was up-regulated, while the nuclear factor
      kappaB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) mRNA
      levels were down-regulated by TSG. Furthermore, TSG activated the phosphoinosmde
      3-kinase/protein kinase B (also known as PI3K/Akt) pathway, and blocking this
      pathway by the inhibitor LY-294002 could impair TSG's functions in relation to
      the MC3T3-E1 cells. In conclusion, TSG could activate the PI3K/Akt pathway and
      thus promote MC3T3-E1 cell proliferation and differentiation, and influence
      OPG/RANKL/M-CSF expression. TSG merits further investigation as a potential
      therapeutic agent for osteoporosis treatment.

PMID- 30201909
TI  - The In Vitro Anti-Proliferative Interaction of Flavonoid Quercetin and Toxic
      Metal Cadmium in the 1321N1 Human Astrocytoma Cell Line.
AB  - Cadmium (Cd) is a toxic heavy metal occurring in the environment as an industrial
      pollutant. The systematic accumulation of Cd in the human body may lead to major
      health problems. Quercetin (QE) is a natural flavonoid widely distributed in
      plants and is a part of human diet. Many studies have demonstrated the multiple
      benefits of QE to humans in protecting cells of our bodies. The aim of this study
      was to investigate the effect of QE and Cd on the proliferation of astrocytoma
      1321N1 cells. Results indicated that the simultaneous exposure of the cells to
      200 uM QE and 16 MUM Cd significantly reduced cell viability to 6.9 +/- 1.6% with
      respect to vehicle-treated cells. Other experiments of QE pre-treatment followed
      by the exposure to Cd alone or with QE indicated significant but decreased
      ability of QE or Cd to reduce proliferation of the cells compared to their co
      incubation. Our study suggested a synergetic anti-proliferative interaction of Cd
      and QE in malignantly transformed cells. This adds new information regarding the
      biological effects of QE.

PMID- 30201910
TI  - Safety of Transcranial Direct Current Stimulation of Frontal, Parietal, and
      Cerebellar Regions in Fasting Healthy Adults.
AB  - (1) Background: Transcranial direct current stimulation (tDCS) is a non-invasive
      brain stimulation modality that has been investigated in a large number of
      studies in terms of it is effects on brain function, safety of use, and future
      implications. The principal aim of this study was to investigate the safety of
      1.5-mA tDCS of three brain areas, that is, frontal, partial, and cerebellar
      cortices, in fasting healthy individuals during the month of Ramadan. (2)
      Methods: In a single-blinded, sham-controlled study, we assessed the safety of a
      20-min tDCS current (1.5 mA, 35 cm2) over the right frontal, parietal, and
      cerebellar cortex areas after 8 h of fasting in healthy right-handed adult
      subjects using a standard safety questionnaire. (3) Results: A total of 49
      subjects completed the tDCS sessions and safety questionnaire. None of the
      sessions were stopped due to pain or discomfort during stimulation. Moreover, no
      subject experienced serious adverse events such as seizures or loss of
      consciousness. (4) Conclusions: There was no significant difference in the
      frequency or type of side effects between active and sham stimulation sessions.
      The tDCS protocol applied in this study was found to be safe in fasting healthy
      adults.

PMID- 30201911
TI  - Quality Evaluation of Phellodendri Chinensis Cortex by Fingerprint-Chemical
      Pattern Recognition.
AB  - Phellodendri Chinensis Cortex (PCC) and Phellodendri Amurensis Cortex (PAC) are
      increasingly being used as traditional herbal medicines, but they are often
      mistaken for each other. In this study, the fingerprints of PCC from six
      different geographical sources were obtained by high-performance liquid
      chromatography, and multivariate chemometric methods were used for comprehensive
      analysis. Two unsupervised pattern recognition models (principal component
      analysis and hierarchical cluster analysis) and a supervised pattern recognition
      model (partial least squares discriminant analysis) were established on the basis
      of the chemical composition and physical traits of PCC and PAC. PCC and PAC were
      found to be distinguishable by these methods. The PCC category was divisible into
      two categories, one with more crude cork and a maximum thickness of ~1.5 mm, and
      the other with less net crude cork and a maximum thickness of 0.5 mm. According
      to the model established by partial least squares discriminant analysis (PLS-DA),
      the important chemical marker berberine hydrochloride was obtained and analyzed
      quantitatively. From these results combined with chemometric and content
      analyses, the preliminary classification standards for phellodendron were
      established as three grades: superior, first-order and mixed. Compared with the
      traditional identification methods of thin layer chromatography identification
      and microscopic identification, our method for quality evaluation is relatively
      simple. It provides a basis and reference for identification of PCC and enables
      establishment of grade standards. It also could be applied in quality control for
      compound preparations containing PCC.

PMID- 30201912
TI  - Walnut Protein Hydrolysates Play a Protective Role on Neurotoxicity Induced by d
      Galactose and Aluminum Chloride in Mice.
AB  - In recent years, with an increase in the aging population, neurodegenerative
      diseases have attracted more and more attention. This study aimed to investigate
      the potential neuroprotective effect of defatted walnut meal protein hydrolysates
      (DWMPH) on neurotoxicity induced by d-galactose (d-gal) and aluminum chloride
      (AlCl3) in mice. The animal models were established by combining treatments with
      d-gal (200 mg/kg/day, subcutaneously) and AlCl3 (100 mg/kg in drinking water) for
      90 days. During the 90 days, 1 g/kg of DWMPH was administrated orally every day.
      The results indicated that DWMPH treatment alleviated oxidative stress, reversed
      cholinergic dysfunction, and suppressed the release of proinflammatory cytokines
      in the brains of d-gal + AlCl3-treated mice, and thus improving the learning and
      memory functions of these mice, which was closely correlated with the strong
      antioxidant activity of DWMPH. This finding suggests that DWMPH might be a
      promising dietary supplement in improving neuronal dysfunctions of the brain.

PMID- 30201913
TI  - Gold Rod-Polyethylene Glycol-Carbon Dot Nanohybrids as Phototheranostic Probes.
AB  - Emphasis using phototheranostics has been placed on the construction of
      multifunctional nanoplatforms for simultaneous tumor diagnosis and therapy.
      Herein, we put forth a novel nanosized luminescent material using the
      incorporation of red emissive carbon dots on gold nanorods through polyethylene
      glycol as a covalent linkage for dual-modal imaging and photothermal therapy. The
      novel nanohybrids, not only retain the optical properties of the gold nanorod and
      carbon dots, but also possess superior imaging performance in both confocal laser
      scanning microscopy and fluorescence lifetime imaging microscopy. The nanohybrids
      also exhibit excellent photothermal performance as phototheranostic nanohybrid
      probes for in vitro assays. This study promises a new multifunctional
      nanoplatform for cancer diagnostics and therapeutics.

PMID- 30201914
TI  - Ionizing Radiation and Human Health: Reviewing Models of Exposure and Mechanisms
      of Cellular Damage. An Epigenetic Perspective.
AB  - We reviewed available evidence in medical literature concerning experimental
      models of exposure to ionizing radiations (IR) and their mechanisms of producing
      damages on living organisms. The traditional model is based on the theory of
      "stochastic breakage" of one or both strands of the DNA double helix. According
      to this model, high doses may cause the breaks, potentially lethal to the cell by
      damaging both DNA strands, while low doses of IR would cause essentially single
      strands breaks, easily repairable, resulting in no permanent damages. The
      available evidence makes this classical model increasingly less acceptable,
      because the exposure to low doses of IR seems to have carcinogenic effects, even
      after years or decades, both in the exposed individuals and in subsequent
      generations. In addition, the cells that survived the exposure to low doses,
      despite being apparently normal, accumulate damages that become evident in their
      progeny, such as nonclonal chromosomal aberrations, which can be found even in
      cells not directly irradiated due to the exchange of molecular signals and
      complex tissue reactions involving neighboring or distant cells. For all these
      reasons, a paradigm shift is needed, based on evidence and epigenetics.

PMID- 30201916
TI  - Application of Ionic Liquid-Based Ultrasonic-Assisted Extraction of Flavonoids
      from Bamboo Leaves.
AB  - Ionic liquids (ILs), known as environmentally benign "green" solvents, were
      developed as an optimal solvent for the green extraction and separation field. In
      this paper, an ionic liquid-based ultrasonic-assisted extraction (IL-UAE) of
      flavonoids (FVs) from bamboo leaves of Phyllostachys heterocycla was developed
      for the first time. First, 1-butyl-3-methylimidazolium bromide ([Bmim] Br), with
      the best extraction efficiency, was selected from fifteen ionic liquids with
      diverse structure, like carbon chains or anions. Then, the influencing parameters
      of ionic liquid (IL) concentration, liquid-solid ratio, ultrasonic time, and
      ultrasonic power, were investigated by single factor tests, and further optimized
      using response surface methodology (RSM). In the optimization experiment, the
      best conditions were 1.5 mol/L [BMIM]Br aqueous solution, liquid-solid ratio 41
      mL/g, ultrasonic time 90 min, and ultrasonic power 300 W. Furthermore, the
      microstructures of bamboo leaves and the recovery of FVs and [BMIM]Br were also
      studied. Therefore, this simple, green and effective IL-UAE method has
      potentiality for the extraction of FVs from bamboo leaves for the large-scale
      operations.

PMID- 30201917
TI  - A High-Throughput Study of the Electronic Structure and Physical Properties of
      Short-Period (GaAs)m(AlAs)n (m, n <= 10) Superlattices Based on Density
      Functional Theory Calculations.
AB  - As important functional materials, the electronic structure and physical
      properties of (GaAs)m(AlAs)n superlattices (SLs) have been extensively studied.
      However, due to limitations of computational methods and computational resources,
      it is sometimes difficult to thoroughly understand how and why the modification
      of their structural parameters affects their electronic structure and physical
      properties. In this article, a high-throughput study based on density functional
      theory calculations has been carried out to obtain detailed information and to
      further provide the underlying intrinsic mechanisms. The band gap variations of
      (GaAs)m(AlAs)n superlattices have been systematically investigated and
      summarized. They are very consistent with the available reported experimental
      measurements. Furthermore, the direct-to-indirect-gap transition of
      (GaAs)m(AlAs)n superlattices has been predicted and explained. For certain
      thicknesses of the GaAs well (m), the band gap value of (GaAs)m(AlAs)n SLs
      exponentially increases (increasing n), while for certain thicknesses of the AlAs
      barrier (n), the band gap value of (GaAs)m(AlAs)n SLs exponentially decreases
      (increasing m). In both cases, the band gap values converge to certain values.
      Furthermore, owing to the energy eigenvalues at different k-points showing
      different variation trends, (GaAs)m(AlAs)n SLs transform from a Gamma-Gamma
      direct band gap to Gamma-M indirect band gap when the AlAs barrier is thick
      enough. The intrinsic reason for these variations is that the contributions and
      positions of the electronic states of the GaAs well and the AlAs barrier change
      under altered thickness conditions. Moreover, we have found that the binding
      energy can be used as a detector to estimate the band gap value in the design of
      (GaAs)m(AlAs)n devices. Our findings are useful for the design of novel
      (GaAs)m(AlAs)n superlattices-based optoelectronic devices.

PMID- 30201915
TI  - The "Frail" Brain Blood Barrier in Neurodegenerative Diseases: Role of Early
      Disruption of Endothelial Cell-to-Cell Connections.
AB  - The main neurovascular unit of the Blood Brain Barrier (BBB) consists of a
      cellular component, which includes endothelial cells, astrocytes, pericytes,
      microglia, neurons, and oligodendrocytes as well as a non-cellular component
      resulting from the extracellular matrix. The endothelial cells are the major
      vital components of the BBB able to preserve the brain homeostasis. These cells
      are situated along the demarcation line between the bloodstream and the brain.
      Therefore, an alteration or the progressive disruption of the endothelial layer
      may clearly impair the brain homeostasis. The proper functioning of the brain
      endothelial cells is generally ensured by two elements: (1) the presence of
      junction proteins and (2) the preservation of a specific polarity involving an
      apical-luminal and a basolateral-abluminal membrane. This review intends to
      identify the molecular mechanisms underlying BBB function and their changes
      occurring in early stages of neurodegenerative processes in order to develop
      novel therapeutic strategies aimed to counteract neurodegenerative disorders.

PMID- 30201919
TI  - A Sensor Control Model for Cabled Seafloor Observatories in the East China Sea.
AB  - Seafloor observatories enable real-time, continuous and long-term observations
      that promise major breakthroughs in ocean sciences. The effort to dynamically
      control in situ sensor systems performing individual and cooperative observation
      tasks is both a challenge and a guarantee for the stable operations of functional
      observatories. However, current sensor control systems for seafloor observatories
      are application-oriented and focus on specific engineering requirements rather
      than general model research. In this paper, a sensor control model was proposed
      to provide a theoretical specification for designing, developing and deploying a
      sensor control system for cabled seafloor observatories. The model abstracted the
      sensor control as a standardized bidirectional information flow process and
      accordingly structured the control system into the application layer, the service
      layer, the networking layer, and the sensing layer. The layered functions and
      interactions between adjacent layers in return realized this information process.
      A prototype control system was designed and developed, the monitoring
      architecture of which was derived from one of the deployment scenarios of the
      sensor control model. The prototype system was tested for its plug-and-play
      enablement through a series of trials such as tank tests and shallow sea trials.
      It was put into service for the operational Xiaoqushan Seafloor Observatory and
      was consistently functioning and presenting satisfactory practical performance in
      accordance with all the requirements laid for the project.

PMID- 30201918
TI  - Venomous Arachnid Diagnostic Assays, Lessons from Past Attempts.
AB  - Diagnostic tests for arachnid accidents remain unavailable for patients and
      clinicians. Together with snakes, these accidents are still a global medical
      concern, and are recognized as neglected tropical issues. Due to arachnid toxins'
      fast mechanism of action, quick detection and quantification of venom is required
      to accelerate treatment decisions, rationalize therapy, and reduce costs and
      patient risks. This review aims to understand the current limitations for
      arachnid venom identification and quantification in biological samples. We
      benchmarked the already existing initiatives regarding test requirements (sample
      or biomarkers of choice), performances (time, detection limit, sensitivity and
      specificity) and their validation (on animal models or on samples from envenomed
      humans). Our analysis outlines unmet needs for improving diagnosis and
      consequently treatment of arachnid accidents. Hence, based on lessons from past
      attempts, we propose a road map for raising best practice guidelines, leading to
      recommendations for future progress in the development of arachnid diagnostic
      assays.

PMID- 30201922
TI  - Vehicle Collision Prediction under Reduced Visibility Conditions.
AB  - Rear-end collisions often cause serious traffic accidents. Conventionally, in
      intelligent transportation systems (ITS), radar collision warning methods are
      highly accurate in determining the inter-vehicle distance via detecting the rear
      end of a vehicle; however, in poor weather conditions such as fog, rain, or snow,
      the accuracy is significantly affected. In recent years, the advent of Vehicle to
      Vehicle (V2V) and Vehicle to Infrastructure (V2I) communication systems has
      introduced new methods for solving the rear-end collision problem. Nevertheless,
      there is still much left for improvement. For instance, weather conditions have
      an impact on human-related factors such as response time. To address the issue of
      collision detection under low visibility conditions, we propose a Visibility
      based Collision Warning System (ViCoWS) design that includes four models for
      prediction horizon estimation, velocity prediction, headway distance prediction,
      and rear-end collision warning. Based on the history of velocity data, future
      velocity volumes are predicted. Then, the prediction horizon (number of future
      time slots to consider) is estimated corresponding to different weather
      conditions. ViCoWs can respond in real-time to weather conditions with correct
      collision avoidance warnings. Experiment results show that the mean absolute
      percentage error of our velocity prediction model is less than 11%. For non
      congested traffic under heavy fog (very low visibility of 120 m), ViCoWS warns a
      driver by as much as 4.5 s prior to a possible future collision. If the fog is
      medium with a low visibility of 160 m, ViCoWs can give warnings by about 2.1 s
      prior to a possible future collision. In contrast, the Forward Collision
      Probability Index (FCPI) method gives warnings by only about 0.6 s before a
      future collision. For congested traffic under low visibility conditions, ViCoWS
      can warn a driver by about 1.9 s prior to a possible future collision. In this
      case, the FCPI method gives 1.2 s for the driver to react before collision.

PMID- 30201921
TI  - Understanding the Role of Mobile Internet-Based Health Services on Patient
      Satisfaction and Word-of-Mouth.
AB  - With the rapid advancement of Web 2.0 technologies, Internet medicine, and mobile
      healthcare, the influence of the use of patient-oriented Mobile Internet-based
      Health Services (MIHS) on patient satisfaction and the electronic word-of-mouth
      (WOM) of health service agencies is becoming the focus of the academic research
      community. Many large hospitals, including some Internet hospitals, have provided
      various online healthcare service platforms that enable patients to expediently
      consult with physicians and obtain healthcare services in an online to offline
      format. The purpose of this study is to analyze the main mechanisms of how the
      features and users' experiences of MIHS influenced patient satisfaction and
      continuous use behaviors of the system to generate additional WOM dissemination
      behaviors. Based on post-adoption behavior and Expectation Confirmation Model of
      Information Technology Continuance (ECM-IT), this study conducted an empirical
      study through data collection from users (patients) from a large hospital
      providing online healthcare services. A total of 494 pieces of data were
      collected and analyzed using SmartPLS2.0(SmartPLS GmbH, Hamburg, Gernmany). The
      results show that: (1) patient satisfaction with MIHS and their intentions to
      continue use of MIHS have significantly positive influences on WOM; (2) patient
      satisfaction with MIHS is positively influenced by perceived usefulness and
      confirmation of MIHS performance expectations; (3) and patient intentions to
      continue use of MIHS are also affected by some technology factors, such as
      facilitating conditions and perceived risk, as well as some subjective feelings,
      such as perceived usefulness and perceived interactivity. The results of this
      study provide important implications for both research and practice of public
      health.

PMID- 30201920
TI  - Targeting CD46 Enhances Anti-Tumoral Activity of Adenovirus Type 5 for Bladder
      Cancer.
AB  - CD46 is generally overexpressed in many human cancers, representing a prime
      target for CD46-binding adenoviruses (Ads). This could help to overcome low anti
      tumoral activity by coxsackie-adenoviral receptor (CAR)-targeting cancer gene
      therapy viruses. However, because of scarce side-by-side information about CAR
      and CD46 expression levels in cancer cells, mixed observations of cancer
      therapeutic efficacy have been observed. This study evaluated Ad-mediated
      therapeutic efficacy using either CAR-targeting Ad5 or CD46-targeting Ad5/35
      fiber chimera in bladder cancer cell lines. Compared with normal urothelia,
      bladder cancer tissue generally overexpressed both CAR and CD46. While CAR
      expression was not correlated with disease progression, CD46 expression was
      inversely correlated with tumor grade, stage, and risk grade. In bladder cancer
      cell lines, expression levels of CD46 and CAR were highly correlated with Ad5/35-
      and Ad5-mediated gene transduction and cytotoxicity, respectively. In a human EJ
      bladder cancer xenograft mouse model, with either overexpressed or suppressed
      CD46 expression levels, Ad5/35-tk followed by ganciclovir (GCV) treatment
      significantly affected tumor growth, whereas Ad5-tk/GCV had only minimal effects.
      Overall, our findings suggest that bladder cancer cells overexpress both CAR and
      CD46, and that adenoviral cancer gene therapy targeting CD46 represents a more
      suitable therapy option than a CAR-targeting therapy, especially in patients with
      low risk bladder cancers.

PMID- 30201923
TI  - Time Slot Utilization for Efficient Multi-Channel MAC Protocol in VANETs.
AB  - In vehicular ad hoc networks (VANETs), many schemes for a multi-channel media
      access control (MAC) protocol have been proposed to adapt to dynamically changing
      vehicle traffic conditions and deliver both safety and non-safety packets. One
      such scheme is to employ both time-division multiple access (TDMA) and carrier
      sense multiple access (CSMA) schemes (called a hybrid TDMA/CSMA scheme) in the
      control channel (CCH) interval. The scheme can adjust the length of the TDMA
      period depending on traffic conditions. In this paper, we propose a modified
      packet transmitted in the TDMA period to reduce transmission overhead under a
      hybrid TDMA/CSMA multi-channel MAC protocol. Simulation results show that a MAC
      protocol with a modified packet supports an efficient packet delivery ratio of
      control packets in the CCH. In addition, we analyze the hybrid TDMA/CSMA multi
      channel MAC protocol with the modified packet under saturated throughput
      conditions on the service channels (SCHs). The analysis results show that the
      number of neighbors has little effect on the establishment of the number of time
      slots in TDMA periods and on SCHs under saturated throughput conditions.

PMID- 30201925
TI  - A Magnetic Adsorbent for the Removal of Cationic Dyes from Wastewater.
AB  - In this article, a study was presented on the adsorption activity of a new
      nanocomposite particle Fe3O4@1, which was synthesized by combining
      [Cu(HL)2]2H2[P2Mo5O23].10H2O (1) (HL = 2-acetylpyridine semicarbazone) and Fe3O4
      nanoparticles. Transmission electron microscopy and X-ray powder diffraction
      analyses revealed that Fe3O4@1 possessed high crystallinity with an average
      particle size of 19.1 nm. The adsorption activity of the as-prepared Fe3O4@1 was
      investigated by photometrically monitoring the removal of methylene blue,
      rhodamine B, safranine T, gentian violet, fuchsin basic, and methyl orange from
      aqueous solutions. Significantly, we could easily separate Fe3O4@1 from the
      reaction media by applying an external magnet. Furthermore, the recycling
      performance was observed using methylene blue, revealing the recyclability and
      high stability of Fe3O4@1. It was shown that Fe3O4@1 is a promising candidate
      material for adsorbing cationic dyes in aqueous media.

PMID- 30201924
TI  - Clinical and Electrophysiological Differences between Subjects with Dysphonetic
      Dyslexia and Non-Specific Reading Delay.
AB  - Reading is essentially a two-channel function, requiring the integration of
      intact visual and auditory processes both peripheral and central. It is essential
      for normal reading that these component processes go forward automatically. Based
      on this model, Boder described three main subtypes of dyslexia: dysphonetic
      dyslexia (DD), dyseidetic, mixed and besides a fourth group defined non-specific
      reading delay (NSRD). The subtypes are identified by an algorithm that considers
      the reading quotient and the % of errors in the spelling test. Chiarenza and
      Bindelli have developed the Direct Test of Reading and Spelling (DTRS), a
      computerized, modified and validated version to the Italian language of the Boder
      test. The sample consisted of 169 subjects with DD and 36 children with NSRD. The
      diagnosis of dyslexia was made according to the DSM-V criteria. The DTRS was used
      to identify the dyslexia subtypes and the NSRD group. 2-5 min of artefact-free
      EEG (electroencephalogram), recorded at rest with eyes closed, according to 10-20
      system were analyzed. Stability based Biomarkers identification methodology was
      applied to the DTRS and the quantitative EEG (QEEG). The reading quotients and
      the errors of the reading and spelling test were significantly different in the
      two groups. The DD group had significantly higher activity in delta and theta
      bands compared to NSRD group in the frontal, central and parietal areas
      bilaterally. The classification equation for the QEEG, both at the scalp and the
      sources levels, obtained an area under the robust Receiver Operating Curve (ROC)
      of 0.73. However, we obtained a discrimination equation for the DTRS items which
      did not participate in the Boder classification algorithm, with a specificity and
      sensitivity of 0.94 to discriminate DD from NSRD. These results demonstrate for
      the first time the existence of different neuropsychological and
      neurophysiological patterns between children with DD and children with NSRD. They
      may also provide clinicians and therapists warning signals deriving from the
      anamnesis and the results of the DTRS that should lead to an earlier diagnosis of
      reading delay, which is usually very late diagnosed and therefore, untreated
      until the secondary school level.

PMID- 30201926
TI  - Soft Coral Dendronephthya puetteri Extract Ameliorates Inflammations by
      Suppressing Inflammatory Mediators and Oxidative Stress in LPS-Stimulated
      Zebrafish.
AB  - Marine-derived extract and/or bioactive compounds have attracted increasing
      demand due to their unique and potential uses as cures for various inflammation
      based diseases. Several studies revealed anti-inflammatory candidates found in
      soft corals. However, the effects of soft corals on inflammation in an in vivo
      model remain to be determined. Therefore, the extract of soft coral
      Dendronephthya puetteri (DPE) was investigated for an in vivo anti-inflammatory
      effect in a lipopolysaccharide (LPS)-stimulated zebrafish model to determine its
      potential use as a natural anti-inflammatory agent. We also investigated whether
      DPE has toxic effects in a zebrafish model. No significant changes were observed
      in terms of survival, heart beat rate, or developmental abnormalities in the
      zebrafish embryos exposed to a concentration below 100 ug/mL of DPE. Treating the
      zebrafish model with LPS-treatment significantly increased the ROS, NO
      generation, and cell death. However, DPE inhibited this LPS-stimulated ROS, NO
      generation, and cell death in a dose-dependent manner. In addition, DPE
      significantly reduced the mRNA expression of both iNOS and COX-2 and markedly
      suppressed the expression levels of the proinflammatory cytokines, TNF-alpha and
      IL-6, in an LPS-stimulated zebrafish model. These findings demonstrate that DPE
      has profound anti-inflammatory effect in vivo, suggesting that DPE might be a
      strong natural anti-inflammatory agent.

PMID- 30201927
TI  - The Association of Built Environment and Physical Activity in Older Adults: Using
      a Citywide Public Housing Scheme to Reduce Residential Self-Selection Bias.
AB  - Previous studies have documented numerous health benefits of conducting regular
      physical activity among older adults. The built environment is believed to be a
      key factor that can hinder or facilitate daily physical activity, such as walking
      and exercising. However, most empirical studies focusing on environment-physical
      activity associations exhibited residential self-selection bias with cross
      sectional research design, engendering doubts about the impact of built
      environment on physical activity. To reduce this bias, we assessed physical
      activity behaviors of 720 Hong Kong older adults (>=65 years) residing in 24
      public housing estates. The Hong Kong public housing scheme currently provides
      affordable rental flats for 2.1 million people or approximate 30% of total
      population. The applicants were allocated to one of 179 housing estates largely
      by family size and flat availability. Built environment characteristics were
      measured following the '5Ds' principle: (street network) design, (land-use)
      diversity, density, distance to transit, and destination accessibility.
      Multilevel mixed models were used to explore the associations between the built
      environment and the different domains of physical activity (transportation
      walking, recreational walking, and recreational moderate-to-vigorous physical
      activity (MVPA) while controlling for potential estate-level socioeconomic and
      individual confounders. We found that transportation walking was positively
      associated with the number of bus stops and the presence of Mass Transit Railway
      (MTR) stations. Recreational MVPA was positively related to the number of
      recreational facilities. However, land-use mix was negatively related to
      transportation walking, recreational walking, and recreational MVPA. The findings
      of this study support a threshold effect in the environment-physical activity
      associations. Furthermore, large-scale public housing schemes involving random or
      semi-random residence assignment in many cities may provide opportunities to
      explore built environments and physical activity behavior, with the potential to
      overcome residential self-selection bias.

PMID- 30201929
TI  - Strategic Uses of Facebook in Zika Outbreak Communication: Implications for the
      Crisis and Emergency Risk Communication Model.
AB  - While social media has been increasingly used for communication of infectious
      disease outbreaks, little is known about how social media can improve strategic
      communication across various stages of the health crisis. The Crisis and
      Emergency Risk Communication Model (Reynolds & Seeger, 2005; CERC) outlines
      strategies across different crisis phases and can guide crisis communication on
      social media. This research therefore investigates how social media can be
      utilized to implement and adapt the CERC model, by examining the strategic uses
      of Facebook in communicating the recent Zika epidemic by health authorities in
      Singapore. Zika-related Facebook posts of three main Singapore health agencies
      published within the one year period from January 2016 to December 2016 were
      thematically analysed. Results suggest that Facebook was used to communicate the
      crisis strategically, which supported and added to the CERC model. Novel uses of
      Facebook for outbreak communication were demonstrated, including promoting public
      common responsibility for disease prevention and expressing regards to the public
      for cooperation. Results also suggested that preparedness messages might be the
      most effective, as they produced a great level of public engagement. The
      adaptability of the CERC model in social media contexts to improve crisis
      communication is discussed.

PMID- 30201928
TI  - miR-9-5p in Nephrectomy Specimens is a Potential Predictor of Primary Resistance
      to First-Line Treatment with Tyrosine Kinase Inhibitors in Patients with
      Metastatic Renal Cell Carcinoma.
AB  - Approximately 20-30% of patients with metastatic renal cell carcinoma (mRCC) in
      first-line treatment with tyrosine kinase inhibitors (TKIs) do not respond due to
      primary resistance to this drug. At present, suitable robust biomarkers for
      prediction of a response are not available. Therefore, the aim of this study was
      to evaluate a panel of microRNAs (miRNAs) in nephrectomy specimens for use as
      predictive biomarkers for TKI resistance. Archived formalin-fixed, paraffin
      embedded nephrectomy samples from 60 mRCC patients treated with first-line TKIs
      (sunitinib, n = 51; pazopanib, n = 6; sorafenib, n = 3) were categorized into
      responders and non-responders. Using the standard Response Evaluation Criteria in
      Solid Tumors, patients with progressive disease within 3 months after the start
      of treatment with TKI were considered as non-responders and those patients with
      stable disease and complete or partial response under the TKI treatment for at
      least 6 months as responders. Based on a miRNA microarray expression profile in
      the two stratified groups of patients, seven differentially expressed miRNAs were
      validated using droplet digital reverse-transcription quantitative real-time
      polymerase chain reaction (RT-qPCR) assays in the two groups. Receiver operating
      characteristic curve analysis and binary logistic regression of response
      prediction were performed. MiR-9-5p and miR-489-3p were able to discriminate
      between the two groups. MiR-9-5p, as the most significant miRNA, improved the
      correct prediction of primary resistance against TKIs in comparison to that of
      conventional clinicopathological variables. The results of the decision curve
      analyses, Kaplan-Meier analyses and Cox regression analyses confirmed the
      potential of miR-9-5p in the prediction of response to TKIs and the prediction of
      progression-free survival after the initiation of TKI treatment.

PMID- 30201930
TI  - Evaluating Short-Term Musculoskeletal Pain Changes in Desk-Based Workers
      Receiving a Workplace Sitting-Reduction Intervention.
AB  - This paper explores changes in musculoskeletal pain among desk-based workers over
      three months of a workplace-delivered, sitting-reduction intervention.
      Participants (n = 153, 46% female; mean +/- SD aged 38.9 +/- 8.0 years) were
      cluster-randomized (n = 18 work teams) to receive an organizational change
      intervention, with or without an activity tracker. A modified Nordic
      Musculoskeletal Questionnaire assessed pain intensity (0-9; none-worst possible)
      in the neck, upper and lower back, upper and lower extremities, and in total. The
      activPAL3 (7 days, 24 h/day protocol) measured sitting and prolonged sitting in
      >=30 min bouts at work. Mixed models adjusting for cluster and intervention arm
      examined changes in pain (n = 104), and their associations with reductions in
      sitting and prolonged sitting (h/10 h at work) (n = 90). Changes in pain were
      nonsignificant (p >= 0.05) and small for total pain (-0.06 [95% CI: -0.27, 0.16])
      and for each body area (-0.26 [-0.66, 0.15] for upper back to 0.09 [-0.39, 0.56]
      for lower back). Sitting reduction was associated with reduced lower back pain (
      0.84 [-1.44, -0.25] per hour, p = 0.005); other effects were small and non
      significant. No substantial average changes in pain were seen; some improvement
      in lower back pain might be expected with larger sitting reductions. Larger
      samples and diverse interventions are required for more definitive evidence.

PMID- 30201931
TI  - The Electronic Nose's Emerging Role in Respiratory Medicine.
AB  - New interest has grown in the respiratory disorder diagnosis and monitoring,
      throughout electronic nose technologies. This technology has several advantages
      compared to classic approach. In this short letter, we aim to emphasize
      electronic nose role in respiratory medicine.

PMID- 30201932
TI  - Formulation and Evaluation of Silymarin-Loaded Chitosan-Montmorilloite Microbeads
      for the Potential Treatment of Gastric Ulcers.
AB  - Silymarin-loaded mucoadhesive microbeads of Chitosan-MMT were developed using the
      ionotropic gelation technique. Characterization of the microbeads was performed
      by DSC, XRD, SEM, and FTIR techniques. In vitro mucoadhesion and drug release
      studies; gastroprotective studies including the measurement of ulcerative index;
      the determination of gastric wall mucus; and the determination of percentage
      protection, biochemical, and histopathological studies were also performed.
      Microbeads batches were evaluated for particle size (120-140 um), actual drug
      content, (49.36-58.18%) and entrapment efficiency (72.52-92.39%).Biochemical
      estimation of myeloperoxidase was found to be 0.10-0.75 umoles/g/tissue.
      Significant reduction in the ulcerative index showed the gastroprotective effect
      of the formulation. Silymarin-loaded beads of Chitosan-MMT were found to exhibit
      good mucoadhesion and efficient release of the drug, and were found to be a
      promising drug carrier system for the treatment of gastric ulcers.

PMID- 30201933
TI  - An IoT-Oriented Offloading Method with Privacy Preservation for Cloudlet-Enabled
      Wireless Metropolitan Area Networks.
AB  - With the development of the Internet of Things (IoT) technology, a vast amount of
      the IoT data is generated by mobile applications from mobile devices. Cloudlets
      provide a paradigm that allows the mobile applications and the generated IoT data
      to be offloaded from the mobile devices to the cloudlets for processing and
      storage through the access points (APs) in the Wireless Metropolitan Area
      Networks (WMANs). Since most of the IoT data is relevant to personal privacy, it
      is necessary to pay attention to data transmission security. However, it is still
      a challenge to realize the goal of optimizing the data transmission time, energy
      consumption and resource utilization with the privacy preservation considered for
      the cloudlet-enabled WMAN. In this paper, an IoT-oriented offloading method,
      named IOM, with privacy preservation is proposed to solve this problem. The task
      offloading strategy with privacy preservation in WMANs is analyzed and modeled as
      a constrained multi-objective optimization problem. Then, the Dijkstra algorithm
      is employed to evaluate the shortest path between APs in WMANs, and the
      nondominated sorting differential evolution algorithm (NSDE) is adopted to
      optimize the proposed multi-objective problem. Finally, the experimental results
      demonstrate that the proposed method is both effective and efficient.

PMID- 30201934
TI  - Synthesis of Bis(1,2,3-Triazole) Functionalized Quinoline-2,4-Diones.
AB  - Derivatives of 3-(1H-1,2,3-triazol-1-yl)quinoline-2,4(1H,3H)-dione unsubstituted
      on quinolone nitrogen atom, which are available by the previously described four
      step synthesis starting from aniline, were exploited as intermediates in
      obtaining the title compounds. The procedure involves the introduction of
      propargyl group onto the quinolone nitrogen atom of mentioned intermediates by
      the reaction of them with propargyl bromide in N,N-dimethylformamide (DMF) in
      presence of a potassium carbonate and the subsequent formation of a second
      triazole ring by copper catalyzed cyclisation reaction with azido compounds. The
      products were characterized by 1H, 13C and 15N NMR spectroscopy. The
      corresponding resonances were assigned on the basis of the standard 1D and
      gradient selected 2D NMR experiments (1H-1H gs-COSY, 1H-13C gs-HSQC, 1H-13C gs
      HMBC) with 1H-15N gs-HMBC as a practical tool to determine 15N NMR chemical
      shifts at the natural abundance level of 15N isotope.

PMID- 30201935
TI  - Correction: Ameliorative Effects of Grape Seed Proanthocyanidin Extract on Growth
      Performance, Immune Function, Antioxidant Capacity, Biochemical Constituents,
      Liver Histopathology and Aflatoxin Residues in Broilers Exposed to Aflatoxin B1.
      Toxins 2017, 9, 371.
AB  - The authors wish to make the following correction to their paper [...].

PMID- 30201936
TI  - Enhanced Magnetic Properties of BiFeO3 Thin Films by Doping: Analysis of
      Structure and Morphology.
AB  - The improvement of ferromagnetic properties is critical for the practical
      application of multiferroic materials, to be exact, BiFeO3 (BFO). Herein, we have
      investigated the evolution in the structure and morphology of Ho or/and Mn-doped
      thin films and the related diversification in ferromagnetic behavior. BFO,
      Bi0.95Ho0.05FeO3 (BHFO), BiFe0.95Mn0.05O3 (BFMO) and Bi0.95Ho0.05Fe0.95Mn0.05O3
      (BHFMO) thin films are synthesized via the conventional sol-gel method. Density,
      size and phase structure are crucial to optimize the ferromagnetic properties.
      Specifically, under the applied magnetic field of 10 kOe, BHFO and BFMO thin
      films can produce obvious magnetic properties during magnetization and,
      additionally, doping with Ho and Mn (BHFMO) can achieve better magnetic
      properties. This enhancement is attributed to the lattice distortions caused by
      the ionic sizes difference between the doping agent and the host, the generation
      of the new exchange interactions and the inhibition of the antiferromagnetic
      spiral modulated spin structure. This study provides key insights of
      understanding the tunable ferromagnetic properties of co-doped BFO.

PMID- 30201939
TI  - Extensive Experimentations on Opportunistic Routing in Wireless Sensor Networks.
AB  - In this paper, we design and experiment ODYSSE (Opportunistic Duty cYcle based
      routing protocol for wirelesS Sensor nEtworks) protocol. It combines three main
      mechanisms: (i) duty cycle, where nodes alternate between active and sleep
      states, (ii) opportunistic routing where routing tables do not exist and the next
      hop is elected once the packet arrives, and (iii) source coding with LDPC (Low
      Density Parity-Check) codes in order to face packet losses while minimizing
      energy consumption. We focus on two heterogeneous scenarios: bulk image
      transmission and infrequent events reporting. Modeling the average waiting delay
      of forwarders, we show that simple relay selection strategies are effective. We
      used 45 Arduino nodes communicating with IEEE 802.15.4 (XBee) within the large
      platform FIT IoT-LAB (IoT-LAB is part of the large platform FIT: Future Internet
      of Things). We implement and extensively study the behavior and performance of
      our proposal ODYSSE. We show that the three techniques fit perfectly, yielding a
      robust low complexity protocol for highly constrained nodes in typical IoT
      applications.

PMID- 30201940
TI  - An Improved Shapley Value Method for a Green Supply Chain Income Distribution
      Mechanism.
AB  - Low-carbon development and environmental remediation are key factors for green
      resource-based supply chains in China. With this aim in mind, by applying game
      theory under uncertain market demand, this paper incorporates low-carbon
      development and environmental remediation into a resource-based supply chain
      coordination model for decentralized and centralized markets. The results show
      that a centralized market can lead to improvement in total profit. Furthermore,
      based on an improved Shapley value method, a theoretical model for the
      centralized market income distribution mechanism is developed that incorporates
      three corrective risk factors, ecological investment, and technological level.
      Finally, a numerical analysis is conducted using a MATLAB simulation to obtain
      intuitive results, which, in turn, show the validity of incentive income
      distribution mechanisms for green supply chain development in China.

PMID- 30201937
TI  - Gestational Diabetes Alters the Metabolomic Profile in 2nd Trimester Amniotic
      Fluid in a Sex-Specific Manner.
AB  - Maternal diabetes and obesity induce marked abnormalities in glucose homeostasis
      and insulin secretion in the fetus, and are linked to obesity, diabetes, and
      metabolic disease in the offspring, with specific metabolic characterization
      based on offspring sex. Gestational diabetes (GDM) has profound effects on the
      intrauterine milieu, which may reflect and/or modulate the function of the
      maternal-fetal unit. In order to characterize metabolic factors that affect
      offspring development, we profiled the metabolome of second trimester amniotic
      fluid (AF) from women who were subsequently diagnosed with gestational diabetes
      (GDM) using a targeted metabolomics approach, profiling 459 known biochemicals
      through gas chromatography/mass spectrometry (GC/MS) and liquid
      chromatography/mass spectrometry (LC/MS) assays. Using a nested case-control
      study design, we identified 69 total biochemicals altered by GDM exposure, while
      sex-specific analysis identified 44 and 58 metabolites in male and female
      offspring, respectively. The most significant changes were in glucose, amino
      acid, glutathione, fatty acid, sphingolipid, and bile acid metabolism with
      specific changes identified based on the offspring sex. Targeted isotope dilution
      LC/MS confirmatory assays measured significant changes in docosahexaenoic acid
      and arachidonic acid. We conclude that the sex-specific alterations in GDM
      maternal-fetal metabolism may begin to explain the sex-specific metabolic
      outcomes seen in offspring exposed to GDM in utero.

PMID- 30201938
TI  - Ten Key Insights into the Use of Spinal Cord fMRI.
AB  - A comprehensive review of the literature-to-date on functional magnetic resonance
      imaging (fMRI) of the spinal cord is presented. Spinal fMRI has been shown, over
      more than two decades of work, to be a reliable tool for detecting neural
      activity. We discuss 10 key points regarding the history, development, methods,
      and applications of spinal fMRI. Animal models have served a key purpose for the
      development of spinal fMRI protocols and for experimental spinal cord injury
      studies. Applications of spinal fMRI span from animal models across healthy and
      patient populations in humans using both task-based and resting-state paradigms.
      The literature also demonstrates clear trends in study design and acquisition
      methods, as the majority of studies follow a task-based, block design paradigm,
      and utilize variations of single-shot fast spin-echo imaging methods. We,
      therefore, discuss the similarities and differences of these to resting-state
      fMRI and gradient-echo EPI protocols. Although it is newly emerging, complex
      connectivity and network analysis is not only possible, but has also been shown
      to be reliable and reproducible in the spinal cord for both task-based and
      resting-state studies. Despite the technical challenges associated with spinal
      fMRI, this review identifies reliable solutions that have been developed to
      overcome these challenges.

PMID- 30201942
TI  - Quadrant-Based Minimum Bounding Rectangle-Tree Indexing Method for Similarity
      Queries over Big Spatial Data in HBase.
AB  - With the rapid development of mobile devices and sensors, effective searching
      methods for big spatial data have recently received a significant amount of
      attention. Owing to their large size, many applications typically store recently
      generated spatial data in NoSQL databases such as HBase. As the index of HBase
      only supports a one-dimensional row keys, the spatial data is commonly enumerated
      using linearization techniques. However, the linearization techniques cannot
      completely guarantee the spatial proximity of data. Therefore, several studies
      have attempted to reduce false positives in spatial query processing by
      implementing a multi-dimensional indexing layer. In this paper, we propose a
      hierarchical indexing structure called a quadrant-based minimum bounding
      rectangle (QbMBR) tree for effective spatial query processing in HBase. In our
      method, spatial objects are grouped more precisely by using QbMBR and are indexed
      based on QbMBR. The QbMBR tree not only provides more selective query processing,
      but also reduces the storage space required for indexing. Based on the QbMBR tree
      index, two query-processing algorithms for range query and kNN query are also
      proposed in this paper. The algorithms significantly reduce query execution times
      by prefetching the necessary index nodes into memory while traversing the QbMBR
      tree. Experimental analysis demonstrates that our method significantly
      outperforms existing methods.

PMID- 30201941
TI  - High-Dose-Rate Brachytherapy Monotherapy versus Image-Guided Intensity-Modulated
      Radiotherapy with Helical Tomotherapy for Patients with Localized Prostate
      Cancer.
AB  - The aim of this paper is to compare outcomes between high-dose-rate interstitial
      brachytherapy (HDR-BT) monotherapy and image-guided intensity-modulated
      radiotherapy (IG-IMRT) for localized prostate cancer. We examined 353 HDR-BT and
      270 IG-IMRT patients. To reduce background selection bias, we used the method of
      inverse probability treatment weighting (IPTW) with propensity scores. The
      actuarial five-year biochemical failure-free survival rates were 92.9% and 96.7%
      (p = 0.1847; p = 0.077 in IPTW) for HDR-BT and IG-IMRT, respectively; they were
      100% and 95.8% (p = 0.286) for the low-risk group, 95.6% and 92% (p = 0.42) for
      the intermediate-risk group, 90.4% and 84.9% (p = 0.1059; p = 0.04 in IPTW) for
      the high-risk group, and 87.1% and 89.2% (p = 0.3816) for the very-high-risk
      group. In the assessment of accumulated incidences of grade >= 2 toxicity (Common
      Terminology Criteria for Adverse Events version 4.0) at five years, HDR-BT
      monotherapy showed higher genitourinary toxicity (11.9%) than IG-IMRT (3.3%) (p <
      0.0001). The gastrointestinal toxicity was equivalent for HDR-BT (2.3%) and IG
      IMRT (5.5%) (p = 0.063). No Grade 4 or 5 toxicity was detected in either
      modality. HDR-BT showed higher genitourinary toxicity than IG-IMRT. HDR-BT and IG
      IMRT showed equivalent outcomes in low-, intermediate-, and very-high-risk
      groups. For high-risk patients, HDR-BT showed potential to improve prostate
      specific antigen (PSA) control rate compared to IG-IMRT.

PMID- 30201943
TI  - Polyphenols in Liubao Tea Can Prevent CCl4-Induced Hepatic Damage in Mice through
      Its Antioxidant Capacities.
AB  - The present study investigated the preventive effect of polyphenols in Liubao tea
      (PLT) on carbon tetrachloride (CCl4)-induced liver injury in mice. The mice were
      initially treated with PLT, followed by induction of liver injury using 10 mL/kg
      CCl4. Then liver and serum indices, as well as the expression levels of related
      messenger RNAs (mRNAs) and proteins in liver tissues were measured. The results
      showed that PLT reduces the liver quality and indices of mice with liver injury.
      PLT also downregulates aspartate aminotransferase (AST), alanine aminotransferase
      (ALT), triglycerides (TGs), and malondialdehyde (MDA), and upregulates superoxide
      dismutase (SOD) and glutathione peroxidase (GSH-Px) in the sera of mice with
      liver injury. PLT also reduces serum levels of interleukin-6 (IL-6), interleukin
      12 (IL-12), tumor necrosis factor- alpha (TNF- alpha ), and interferon- gamma
      (IFN- gamma ) cytokines in mice with liver injury. Pathological morphological
      observation also shows that PLT reduces CCl4-induced central venous
      differentiation of liver tissues and liver cell damage. Furthermore, qPCR and
      Western blot also confirm that PLT upregulates the mRNA and protein expressions
      of Gu/Zn-SOD, Mn-SOD, catalase (CAT), GSH-Px, and nuclear factor of kappa -light
      polypeptide gene enhancer in B-cells inhibitor- alpha (I kappa B- alpha ) in
      liver tissues, and downregulates the expression of cyclooxygenase 2 (COX-2) and
      nuclear factor kappa -light-chain-enhancer of activated B cells (NF- kappa B).
      Meanwhile, PLT also raised the phosphorylated (p)-NF- kappa B p65 and cytochrome
      P450 reductase protein expression in liver injury mice. The components of PLT
      include gallic acid, catechin, caffeine, epicatechin (EC), epigallocatechin
      gallate (EGCG), gallocatechin gallate (GCG), and epicatechin gallate (ECG), which
      possibly have a wide range of biological activities. Thus, PLT imparts preventive
      effects against CCl4-induced liver injury, which is similar to silymarin.

PMID- 30201945
TI  - Damage Identification for Underground Structure Based on Frequency Response
      Function.
AB  - Damage identification that is based on modal analysis is widely used in
      traditional structural damage identification. However, modal analysis is
      difficult in high damping structures and modal concentrated structures. Unlike
      approaches based on modal analysis, damage identification based on the frequency
      response function allows for the avoidance of error and easy verification through
      other test points. An updating algorithm is devised is this study by utilizing
      the frequency response function together with the dynamic reduction with respect
      to the selected design parameters. Numerical results indicate that the method can
      be used to define multiple parameters with large variation and incomplete
      measurement data and is robust against measurement noise. With the purpose of
      avoiding the occurrence of resonance and gaining additional information, the
      trial and error method has been used to choose a proper frequency. Furthermore,
      an experimental scale model in a soil box is subjected to the excitation of
      moving load to validate the effectiveness of the damage identification approach.
      The improved damage identification method for underground structures, which is
      based on the analysis of the frequency response function, can be adopted as an
      efficient and functional damage identification tool.

PMID- 30201946
TI  - Albumin-Bilirubin Score for Predicting Post-Transplant Complications Following
      Adult-to-Adult Living Donor Liver Transplantation.
AB  - BACKGROUND Albumin-Bilirubin (ALBI) grade has been evaluated as an objective
      method to assess liver function and predict postoperative complications,
      particularly after hepatectomy in patients with hepatocellular carcinoma (HCC).
      However, ALBI grade was rarely used in evaluation in living donor liver
      transplantation (LDLT). MATERIAL AND METHODS Between March 2005 and November
      2015, 272 consecutive patients undergoing right-lobe LDLT were enrolled in this
      study. According to the ALBI score used to evaluate recipients preoperatively,
      those patients were divided into 3 grades (I, II, and III). Demographic findings
      and the post-operative complication rates were collected and compared among
      groups. RESULTS The proportions of massive blood cell transfusions were different
      among those 3 grades (p<0.05). The patients in grade III had a higher risk of
      bacterial pneumonia and early allograft dysfunction (EAD) compared to grade I
      (p=0.029 and p=0.038, respectively) and grade II (p=0.006 and p=0.007,
      respectively). The area under the receiver operating characteristic curve of
      ALBI, Child-Pugh, and MELD for predicting 30-day mortality were 0.702 (95% CI:
      0.644-0.756), 0.669 (95% CI: 0.580-0.697, p=0.510, versus ALBI grade), and 0.540
      (95% CI: 0.580-0.697, p=0.144, versus ALBI grade), respectively. CONCLUSIONS ALBI
      grade was a good index for predicting post-operative complications and had a
      predictive ability similar to those of the Child-Pugh classification and MELD
      score.

PMID- 30201947
TI  - Ventricular Tachycardia (VT) Storm After Cryoballoon-Based Pulmonary Vein
      Isolation.
AB  - BACKGROUND Following catheter ablation of atrial fibrillation, increased
      incidence of ventricular arrhythmia has been observed. We report a case of
      sustained ventricular arrhythmia in a patient who underwent cryoballoon-based
      pulmonary vein isolation for symptomatic persistent atrial fibrillation. CASE
      REPORT A 57-year-old patient with dilated cardiomyopathy underwent CB-based
      pulmonary vein isolation for symptomatic persistent AF. On the day following an
      uneventful procedure, the patient for the first time experienced a sustained
      ventricular tachycardia that exacerbated into VT storm. Each arrhythmia was
      terminated by the ICD that had been implanted for primary prevention.
      Antiarrhythmic treatment with amiodarone was initiated immediately. The patient
      remained free from sustained ventricular arrhythmia during follow-up. CONCLUSIONS
      After pulmonary vein isolation, physicians should be vigilant for ventricular
      arrhythmia. The influence of atrial autonomic innervation on ventricular
      electrophysiology is largely unknown.

PMID- 30201948
TI  - The Expression of Actin-Related Protein 2/3 Complex Subunit 5 (ARPC5) Expression
      in Multiple Myeloma and its Prognostic Significance.
AB  - BACKGROUND The aim of this study was to analyze the prognostic value of ARPC5 in
      patients with multiple myeloma (MM). MATERIAL AND METHODS MM gene expression
      studies GSE6477, GSE31162, GSE24080, and GSE19784 were obtained and analyzed. The
      expression of ARPC5 was assessed in normal plasma cells, baseline MM cells, and
      relapsed MM cells. Univariate and multivariable analyses were used to determine
      the relationship between ARPC5 expression and clinical characteristics and
      survivals of MM patients. Quantitative PCR was used to detect the expression
      ARPC5 in bone marrow mononuclear cells of MM patients and normal controls. GSEA
      was conducted to identify associated mechanisms. RESULTS ARPC5 expression was
      significantly increased in baseline MM cells compared to normal plasma cells
      (P=0.0414). Meanwhile, ARPC5 was significantly increased in relapsed MM cells
      compared to baseline MM cells (P<0.0001). ARPC5 expression was significantly
      associated with beta2-microglobin (P=0.047), serum lactate dehydrogenase
      (P=0.007), and rates of aspirate plasma cells (P=0.007). Meanwhile, patients in
      the ARPC5 high expression group were associated with poor overall survival
      (P=0.0027) and event-free survival (P=0.0102) compared to those in the ARPC5 low
      expression group. Multivariable analysis indicated that ARPC5 was an independent
      prognostic factor for MM patients. Quantitative PCR demonstrated that ARPC5 was
      significantly increased in MM patients. GSEA results indicated that ARPC5 might
      affect cellular growth of myeloma cells through mammalian target of rapamycin
      (mTOR)C1 signaling pathway. CONCLUSIONS ARPC5 could be treated as an independent
      biomarker for patients with MM.

PMID- 30201944
TI  - Control of Biofilm Formation in Healthcare: Recent Advances Exploiting Quorum
      Sensing Interference Strategies and Multidrug Efflux Pump Inhibitors.
AB  - Biofilm formation in healthcare is an issue of considerable concern, as it
      results in increased morbidity and mortality, imposing a significant financial
      burden on the healthcare system. Biofilms are highly resistant to conventional
      antimicrobial therapies and lead to persistent infections. Hence, there is a high
      demand for novel strategies other than conventional antibiotic therapies to
      control biofilm-based infections. There are two approaches which have been
      employed so far to control biofilm formation in healthcare settings: one is the
      development of biofilm inhibitors based on the understanding of the molecular
      mechanism of biofilm formation, and the other is to modify the biomaterials which
      are used in medical devices to prevent biofilm formation. This review will focus
      on the recent advances in anti-biofilm approaches by interrupting the quorum
      sensing cellular communication system and the multidrug efflux pumps which play
      an important role in biofilm formation. Research efforts directed towards these
      promising strategies could eventually lead to the development of better anti
      biofilm therapies than the conventional treatments.

PMID- 30201949
TI  - Extracellular vesicles from pluripotent stem cell-derived mesenchymal stem cells
      acquire a stromal modulatory proteomic pattern during differentiation.
AB  - Mesenchymal stem/stromal cells (MSCs) obtained from pluripotent stem cells (PSCs)
      constitute an interesting alternative to classical MSCs in regenerative medicine.
      Among their many mechanisms of action, MSC extracellular vesicles (EVs) are a
      potential suitable substitute for MSCs in future cell-free-based therapeutic
      approaches. Unlike cells, EVs do not elicit acute immune rejection, and they can
      be produced in large quantities and stored until ready to use. Although the
      therapeutic potential of MSC EVs has already been proven, a thorough
      characterization of MSC EVs is lacking. In this work, we used a label-free liquid
      chromatography tandem mass spectrometry proteomic approach to identify the most
      abundant proteins in EVs that are secreted from MSCs derived from PSCs (PD-MSCs)
      and from their parental induced PSCs (iPSCs). Next, we compared both datasets and
      found that while iPSC EVs enclose proteins that modulate RNA and microRNA
      stability and protein sorting, PD-MSC EVs are rich in proteins that organize
      extracellular matrix, regulate locomotion, and influence cell-substrate adhesion.
      Moreover, compared to their respective cells, iPSCs and iPSC EVs share a greater
      proportion of proteins, while the PD-MSC proteome appears to be more specific.
      Correlation and principal component analysis consistently aggregate iPSCs and
      iPSC EVs but segregate PD-MSC and their EVs. Altogether, these findings suggest
      that during differentiation, compared with their parental iPSC EVs, PD-MSC EVs
      acquire a more specific set of proteins; arguably, this difference might confer
      their therapeutic properties.

PMID- 30201951
TI  - Low-Temperature Continuous Flow Synthesis of Metal Ammonium Phosphates.
AB  - The synthesis of the high performance inorganic materials essential to the
      quality of modern day life is hindered by traditionalist attitudes and reliance
      on outdated methods such as batch syntheses. While continuous flow methods have
      been extensively adopted in pharmaceutical circles, they remain largely
      unexplored for the preparation of inorganic compounds, despite higher efficiency,
      safety and versatility. In this publication, we demonstrate a step-change for the
      synthesis of metal ammonium phosphates through conversion of the extant batch
      process to a low-temperature continuous regime, exhibiting a tenfold increase in
      throughput combined with a significant decrease in particle size.

PMID- 30201950
TI  - Hepatic Ago2-mediated RNA silencing controls energy metabolism linked to AMPK
      activation and obesity-associated pathophysiology.
AB  - RNA silencing inhibits mRNA translation. While mRNA translation accounts for the
      majority of cellular energy expenditure, it is unclear if RNA silencing regulates
      energy homeostasis. Here, we report that hepatic Argonaute 2 (Ago2)-mediated RNA
      silencing regulates both intrinsic energy production and consumption and disturbs
      energy metabolism in the pathogenesis of obesity. Ago2 regulates expression of
      specific miRNAs including miR-802, miR-103/107, and miR-148a/152, causing
      metabolic disruption, while simultaneously suppressing the expression of genes
      regulating glucose and lipid metabolism, including Hnf1beta, Cav1, and Ampka1.
      Liver-specific Ago2-deletion enhances mitochondrial oxidation and ATP consumption
      associated with mRNA translation, which results in AMPK activation, and improves
      obesity-associated pathophysiology. Notably, hepatic Ago2-deficiency improves
      glucose metabolism in conditions of insulin receptor antagonist treatment, high
      fat diet challenge, and hepatic AMPKalpha1-deletion. The regulation of energy
      metabolism by Ago2 provides a novel paradigm in which RNA silencing plays an
      integral role in determining basal metabolic activity in obesity-associated
      sequelae.

PMID- 30201953
TI  - Cerebral autoregulation and activity after propofol for endotracheal intubation
      in preterm neonates.
AB  - BACKGROUND: Despite increasing use of propofol in neonates, observations on
      cerebral effects are limited. AIM: To investigate cerebral autoregulation (CAR)
      and activity after propofol for endotracheal intubation in preterm neonates.
      METHODS: Twenty-two neonates received propofol before intubation as part of a
      published dose-finding study. Mean arterial blood pressure (MABP), near-infrared
      spectroscopy-derived cerebral oxygenation (rScO2), and amplitude-integrated
      electroencephalography (aEEG) were analyzed until 180 min after propofol. CAR was
      expressed as transfer function (TF) gain, indicating % change in rScO2 per 1 mmHg
      change in MABP. Values exceeding mean TF gain + 2 standard deviations (SD)
      defined impaired CAR. RESULTS: After intubation with a median propofol dose of 1
      (0.5-4.5) mg/kg, rScO2 remained stable during decreasing MABP. Mean (+/-SD) TF
      gain was 0.8 (+/-0.3)%/mmHg. Impaired CAR was identified in 1 and 5 patient(s)
      during drug-related hypotension and normal to raised MABP, respectively.
      Suppressed aEEG was observed up to 60 min after propofol. CONCLUSIONS: Drug
      related hypotension and decreased cerebral activity after intubation with low
      propofol doses in preterm neonates were observed, without evidence of cerebral
      ischemic hypoxia. CAR remained intact during drug-related hypotension in 95.5% of
      patients. Cerebral monitoring including CAR clarifies the cerebral impact of MABP
      fluctuations.

PMID- 30201952
TI  - Exogenous application of calcium to 24-epibrassinosteroid pre-treated tomato
      seedlings mitigates NaCl toxicity by modifying ascorbate-glutathione cycle and
      secondary metabolites.
AB  - The present study tested the efficacy of 24-epibrassinolide (EBL) and calcium
      (Ca) for mediating salinity tolerance in tomato. Salinity stress affected the
      morphological parameters of tomato as well as leaf relative water content (LRWC),
      photosynthetic and accessory pigments, leaf gas exchange parameters, chlorophyll
      fluorescence and the uptake of essential macronutrients. The salt (NaCl)
      treatment induced oxidative stress in the form of increased Na+ ion concentration
      by 146%, electrolyte leakage (EL) by 61.11%, lipid peroxidation (MDA) 167% and
      hydrogen peroxide (H2O2) content by 175%. Salt stress also enhanced antioxidant
      enzyme activities including those in the ascorbate-glutathione cycle. Plants
      treated with EBL or Ca after salt exposure mitigated the ill effects of salt
      stress, including oxidative stress, by reducing the uptake of Na+ ions by 52%.
      The combined dose of EBL + Ca reversed the salt-induced changes through an
      elevated pool of enzymes in the ascorbate-glutathione cycle, other antioxidants
      (superoxide dismutase, catalase), and osmoprotectants (proline, glycine betaine).
      Exogenously applied EBL and Ca help to optimize mineral nutrient status and
      enable tomato plants to tolerate salt toxicity. The ability of tomato plants to
      tolerate salt stress when supplemented with EBL and Ca was attributed to
      modifications to enzymatic and non-enzymatic antioxidants, osmolytes and
      metabolites.

PMID- 30201954
TI  - Different patterns of clonal evolution among different sarcoma subtypes followed
      for up to 25 years.
AB  - To compare clonal evolution in tumors arising through different mechanisms, we
      selected three types of sarcoma-amplicon-driven well-differentiated liposarcoma
      (WDLS), gene fusion-driven myxoid liposarcoma (MLS), and sarcomas with complex
      genomes (CXS)-and assessed the dynamics of chromosome and nucleotide level
      mutations by cytogenetics, SNP array analysis and whole-exome sequencing. Here we
      show that the extensive single-cell variation in WDLS has minor impact on clonal
      key amplicons in chromosome 12. In addition, only a few of the single nucleotide
      variants in WDLS were present in more than one lesion, suggesting that such
      mutations are of little significance in tumor development. MLS displays few
      mutations other than the FUS-DDIT3 fusion, and the primary tumor is genetically
      sometimes much more complex than its relapses, whereas CXS in general shows a
      gradual increase of both nucleotide- and chromosome-level mutations, similar to
      what has been described in carcinomas.

PMID- 30201955
TI  - Molecular basis for disassembly of an importin:ribosomal protein complex by the
      escortin Tsr2.
AB  - Disordered extensions at the termini and short internal insertions distinguish
      eukaryotic ribosomal proteins (r-proteins) from their anucleated archaeal
      counterparts. Here, we report an NMR structure of such a eukaryotic-specific
      segment (ESS) in the r-protein eS26 in complex with the escortin Tsr2. The
      structure reveals how ESS attracts Tsr2 specifically to importin:eS26 complexes
      entering the nucleus in order to trigger non-canonical RanGTP-independent
      disassembly. Tsr2 then sequesters the released eS26 and prevents rebinding to the
      importin, providing an alternative allosteric mechanism to terminate the process
      of nuclear import. Notably, a Diamond-Blackfan anemia-associated Tsr2 mutant
      protein is impaired in binding to ESS, unveiling a critical role for this
      interaction in human hematopoiesis. We propose that eS26-ESS and Tsr2 are
      components of a nuclear sorting system that co-evolved with the emergence of the
      nucleocytoplasmic barrier and transport carriers.

PMID- 30201956
TI  - Frequent functional activation of RAS signalling not explained by RAS/RAF
      mutations in relapsed/refractory multiple myeloma.
AB  - RAS mutations are frequent in relapsed/refractory multiple myeloma (RRMM) but
      functional study in primary samples is scanty. Herein, in primary myeloma plasma
      cells of 17 suspected RRMM, functional activation of RAS signalling was studied
      by Western blot of phosphorylated ERK1/2 (phospho-ERK1/2). Moreover, activating
      mutations in KRAS, NRAS, BRAF, and ALK were studied by PCR and bidirectional
      direct sequencing. Furthermore, methylation of negative RAS signalling regulator
      genes, RASSF1A and RASD1, were analyzed by methylation-specific PCR. As evidenced
      by phospho-ERK1/2 over-expression, functional RAS activation was detected in 12
      (75.0%) RRMM. Of patients with functional RAS activation, sequencing data showed
      only seven (58.3%) patients with one each had NRAS Q61H, NRAS Q61K, KRAS G12D,
      KRAS G12V, KRAS G13D, KRAS Q61P, or BRAF V600E mutation, whereas five (41.7%)
      patients had no RAS/RAF mutation. Conversely, patients without functional RAS
      activation had no RAS/RAF mutation. Moreover, none of the patients with
      functional RAS activation had ALK mutations, or methylation of RASSF1A and RASD1.
      Collectively, functional activation of RAS signalling was present in majority of
      RRMM but only about half (58.3%) accountable by RAS/RAF mutations. If verified in
      larger studies, clinical investigations of MEK inhibitors are warranted
      regardless of RAS/RAF mutations.

PMID- 30201958
TI  - A method of determining heated ancient nephrite jades in China.
AB  - Ancient jade is one of the most significant cultural relics in China. Despite the
      increasingly important role of heated jades in ancient jade study, there are
      still few in-depth material studies on heated jades for the time being, which
      results in limitations on archaeological research and conservation. In order to
      evaluate the appearance change of nephrite jades, we employ the heating
      simulation experiment to present these change under different heating temperature
      ranging from 100  degrees C to 1300  degrees C. In this study, a nondestructive
      identification method proposed is to help determine whether the ancient jades
      were heated before and what the approximate heating temperature was from 100 
      degrees C to 1300  degrees C though phase transformation, structure change and
      colour variation with several advanced characterization methods such as the X-ray
      diffraction (XRD), the thermo-gravimetric analyser (TGA), the ultraviolet-visible
      spectrophotometer (UV-Vis), the Fourier transform infrared spectroscopy (FTIR)
      and the scanning electron microscope (SEM). The hierarchy of colour (from ~500 
      degrees C) and structure (from ~800  degrees C) on heated jades in the jade
      research field were first proposed and discuss here. This method is considered
      useful and valuable in the study and protection of Chinese ancient jades.

PMID- 30201957
TI  - Solid-state random microlasers fabricated via femtosecond laser writing.
AB  - Here we demonstrate resonant random lasing in Rhodamine B-doped polymeric
      microstructures fabricated by means of femtosecond laser writing via two-photon
      polymerization. To the best of our knowledge, this is the first demonstration of
      random lasing action in on-chip microdevices. Their feedback mechanism relies on
      diffuse reflections at the structure sidewall surfaces, which is known as
      spatially localized feedback since the scattering centers lie over the edges of
      the gain medium. By exciting the structures with a pulsed laser at 532 nm, a
      multimode emission with randomly distributed narrow peaks was observed, in
      accordance with the random nature of the feedback mechanism. Interestingly, their
      lasing threshold was found to be on the order of tens of nanojoules, which is
      comparable to what had been achieved for usual microcavities, thereby
      demonstrating the potentiality of these devices as solid-state lasers for
      integrated optics applications.

PMID- 30201959
TI  - A multi-cellular 3D bioprinting approach for vascularized heart tissue
      engineering based on HUVECs and iPSC-derived cardiomyocytes.
AB  - The myocardium behaves like a sophisticated orchestra that expresses its true
      potential only if each member performs the correct task harmonically.
      Recapitulating its complexity within engineered 3D functional constructs with
      tailored biological and mechanical properties, is one of the current scientific
      priorities in the field of regenerative medicine and tissue engineering. In this
      study, driven by the necessity of fabricating advanced model of cardiac tissue,
      we present an innovative approach consisting of heterogeneous, multi-cellular
      constructs composed of Human Umbilical Vein Endothelial Cells (HUVECs) and
      induced pluripotent cell-derived cardiomyocytes (iPSC-CMs). Cells were
      encapsulated within hydrogel strands containing alginate and PEG-Fibrinogen (PF)
      and extruded through a custom microfluidic printing head (MPH) that allows to
      precisely tailor their 3D spatial deposition, guaranteeing a high printing
      fidelity and resolution. We obtained a 3D cardiac tissue compose of iPSC-derived
      CMs with a high orientation index imposed by the different defined geometries and
      blood vessel-like shapes generated by HUVECs which, as demonstrated by in vivo
      grafting, better support the integration of the engineered cardiac tissue with
      host's vasculature.

PMID- 30201960
TI  - T cell immunomodulation by clinically used allogeneic human cancellous bone
      fragments: a potential novel immunotherapy tool.
AB  - Multipotential stromal cells (MSCs) demonstrate strong immunomodulation
      capabilities following culture expansion. We have previously demonstrated that
      human cancellous bone fragments (CBFs) clinically used as viable allografts for
      spinal fusion have resident MSCs that exhibit T cell immunomodulation after
      monolayer expansion. This study investigated the immunomodulatory ability of
      these CBFs without MSC culture-expansion. CD4 positive T cells were induced to
      proliferate using CD3/CD28 stimulation and added to CBFs at different ratios of T
      cells per gram of CBF. A dose-dependent suppressive effect on T cell
      proliferation was evident and correlated with increased culture supernatant
      levels of TGF-beta1, but not PGE2. CBF-driven immunosuppression was reduced in co
      cultures with TGF-beta neutralising antibodies and was higher in cell contact
      compared to non-contact cultures. CBF gene expression profile identified vascular
      cell adhesion molecule-1, bone marrow stromal antigen 2/CD317 and other
      interferon signalling pathway members as potential immunomodulatory mediators.
      The CD317 molecule was detected on the surface of CBF-resident cells confirming
      the gene expression data. Taken together, these data demonstrate that human
      clinically used CBFs are inherently immunomodulatory and suggest that these
      viable allografts may be used to deliver therapeutic immunomodulation for immune
      related diseases.

PMID- 30201962
TI  - Incipient de novo genes can evolve from frozen accidents that escaped rapid
      transcript turnover.
AB  - A recent surge of studies have suggested that many novel genes arise de novo from
      previously noncoding DNA and not by duplication. However, most studies
      concentrated on longer evolutionary time scales and rarely considered protein
      structural properties. Therefore, it remains unclear how these properties are
      shaped by evolution, depend on genetic mechanisms and influence gene survival.
      Here we compare open reading frames (ORFs) from high coverage transcriptomes from
      mouse and another four mammals covering 160 million years of evolution. We find
      that novel ORFs pervasively emerge from noncoding regions but are rapidly lost
      again, while relatively fewer arise from the divergence of coding sequences but
      are retained much longer. We also find that a subset (14%) of the mouse-specific
      ORFs bind ribosomes and are potentially translated, showing that such ORFs can be
      the starting points of gene emergence. Surprisingly, disorder and other protein
      properties of young ORFs hardly change with gene age in short time frames. Only
      length and nucleotide composition change significantly. Thus, some transcribed de
      novo genes resemble 'frozen accidents' of randomly emerged ORFs that survived
      initial purging. This perspective complies with very recent studies indicating
      that some neutrally evolving transcripts containing random protein sequences may
      be translated and be viable starting points of de novo gene emergence.

PMID- 30201965
TI  - Knowing ourselves.

PMID- 30201963
TI  - A plant-microbe interaction framework explaining nutrient effects on primary
      production.
AB  - In most terrestrial ecosystems, plant growth is limited by nitrogen and
      phosphorus. Adding either nutrient to soil usually affects primary production,
      but their effects can be positive or negative. Here we provide a general
      stoichiometric framework for interpreting these contrasting effects. First, we
      identify nitrogen and phosphorus limitations on plants and soil microorganisms
      using their respective nitrogen to phosphorus critical ratios. Second, we use
      these ratios to show how soil microorganisms mediate the response of primary
      production to limiting and non-limiting nutrient addition along a wide gradient
      of soil nutrient availability. Using a meta-analysis of 51 factorial nitrogen
      phosphorus fertilization experiments conducted across multiple ecosystems, we
      demonstrate that the response of primary production to nitrogen and phosphorus
      additions is accurately predicted by our stoichiometric framework. The only
      pattern that could not be predicted by our original framework suggests that
      nitrogen has not only a structural function in growing organisms, but also a key
      role in promoting plant and microbial nutrient acquisition. We conclude that this
      stoichiometric framework offers the most parsimonious way to interpret
      contrasting and, until now, unresolved responses of primary production to
      nutrient addition in terrestrial ecosystems.

PMID- 30201964
TI  - Harold L. Dibble (1951-2018).

PMID- 30201961
TI  - Correction: Arterial tortuosity syndrome: 40 new families and literature review.
AB  - In the published version of this paper the author Neus Baena's name was
      incorrectly given as Neus Baena Diez. This has now been corrected in both the
      HTML and PDF versions of the paper.

PMID- 30201966
TI  - Evolutionary potential of transcription factors for gene regulatory rewiring.
AB  - Gene regulatory networks evolve through rewiring of individual components-that
      is, through changes in regulatory connections. However, the mechanistic basis of
      regulatory rewiring is poorly understood. Using a canonical gene regulatory
      system, we quantify the properties of transcription factors that determine the
      evolutionary potential for rewiring of regulatory connections: robustness,
      tunability and evolvability. In vivo repression measurements of two repressors at
      mutated operator sites reveal their contrasting evolutionary potential: while
      robustness and evolvability were positively correlated, both were in trade-off
      with tunability. Epistatic interactions between adjacent operators alleviated
      this trade-off. A thermodynamic model explains how the differences in robustness,
      tunability and evolvability arise from biophysical characteristics of repressor
      DNA binding. The model also uncovers that the energy matrix, which describes how
      mutations affect repressor-DNA binding, encodes crucial information about the
      evolutionary potential of a repressor. The biophysical determinants of
      evolutionary potential for regulatory rewiring constitute a mechanistic framework
      for understanding network evolution.

PMID- 30201967
TI  - Global change in marine aquaculture production potential under climate change.
AB  - Climate change is an immediate and future threat to food security globally. The
      consequences for fisheries and agriculture production potential are well studied,
      yet the possible outcomes for aquaculture (that is, aquatic farming)-one of the
      fastest growing food sectors on the planet-remain a major gap in scientific
      understanding. With over one-third of aquaculture produced in marine waters and
      this proportion increasing, it is critical to anticipate new opportunities and
      challenges in marine production under climate change. Here, we model and map the
      effect of warming ocean conditions (Representative Concentration Pathway scenario
      8.5) on marine aquaculture production potential over the next century, based on
      thermal tolerance and growth data of 180 cultured finfish and bivalve species. We
      find heterogeneous patterns of gains and losses, but an overall greater
      probability of declines worldwide. Accounting for multiple drivers of species
      growth, including shifts in temperature, chlorophyll and ocean acidification,
      reveals potentially greater declines in bivalve aquaculture compared with finfish
      production. This study addresses a missing component in food security research
      and sustainable development planning by identifying regions that will face
      potentially greater climate change challenges and resilience with regards to
      marine aquaculture in the coming decades. Understanding the scale and magnitude
      of future increases and reductions in aquaculture potential is critical for
      designing effective and efficient use and protection of the oceans, and
      ultimately for feeding the planet sustainably.

PMID- 30201968
TI  - Structure of the herpes simplex virus type 2 C-capsid with capsid-vertex-specific
      component.
AB  - Herpes simplex viruses (HSVs) cause human oral and genital ulcer diseases.
      Patients with HSV-2 have a higher risk of acquiring a human immunodeficiency
      virus infection. HSV-2 is a member of the alpha-herpesvirinae subfamily that
      together with the beta- and gamma-herpesvirinae subfamilies forms the
      Herpesviridae family. Here, we report the cryo-electron microscopy structure of
      the HSV-2 C-capsid with capsid-vertex-specific component (CVSC) that was
      determined at 3.75 A using a block-based reconstruction strategy. We present
      atomic models of multiple conformers for the capsid proteins (VP5, VP23, VP19C,
      and VP26) and CVSC. Comparison of the HSV-2 homologs yields information about
      structural similarities and differences between the three herpesviruses sub
      families and we identify alpha-herpesvirus-specific structural features. The
      hetero-pentameric CVSC, consisting of a UL17 monomer, a UL25 dimer and a UL36
      dimer, is bound tightly by a five-helix bundle that forms extensive networks of
      subunit contacts with surrounding capsid proteins, which reinforce capsid
      stability.

PMID- 30201969
TI  - Association of schizophrenia polygenic risk score with manic and depressive
      psychosis in bipolar disorder.
AB  - Bipolar disorder (BD) is highly heterogeneous in symptomatology. Narrowing the
      clinical phenotype may increase the power to identify risk genes that contribute
      to particular BD subtypes. This study was designed to test the hypothesis that
      genetic overlap between schizophrenia (SZ) and BD is higher for BD with a history
      of manic psychosis. Analyses were conducted using a Mayo Clinic Bipolar Biobank
      cohort of 957 bipolar cases (including 333 with history of psychosis during
      mania, 64 with history of psychosis only during depression, 547 with no history
      of psychosis, and 13 with unknown history of psychosis) and 778 controls.
      Polygenic risk score (PRS) analysis was performed by calculating a SZ-PRS for the
      BD cases and controls, and comparing the calculated SZ risk between different
      psychosis subgroups and bipolar types. The SZ-PRS was significantly higher for BD
      I cases with manic psychosis than BD-I cases with depressive psychosis
      (Nagelkerke's R2 = 0.021; p = 0.045), BD-I cases without psychosis (R2 = 0.015; p
      = 0.007), BD-II cases without psychosis (R2 = 0.014; p = 0.017), and controls (R2
      = 0.065; p = 2 * 10-13). No other significant differences were found. Our results
      show that BD-I with manic psychosis is genetically more similar to SZ than any
      other tested BD subgroup. Further investigations on genetics of distinct clinical
      phenotypes composing major psychoses may help refine the current diagnostic
      classification system.

PMID- 30201970
TI  - Microbial metabolite sensor GPR43 controls severity of experimental GVHD.
AB  - Microbiome-derived metabolites influence intestinal homeostasis and regulate
      graft-versus-host disease (GVHD), but the molecular mechanisms remain unknown.
      Here we show the metabolite sensor G-protein-coupled receptor 43 (GPR43) is
      important for attenuation of gastrointestinal GVHD in multiple clinically
      relevant murine models. GPR43 is critical for the protective effects of short
      chain fatty acids (SCFAs), butyrate and propionate. Increased severity of GVHD in
      the absence of GPR43 is not due to baseline differences in the endogenous
      microbiota of the hosts. We confirm the ability of microbiome-derived metabolites
      to reduce GVHD by several methods, including co-housing, antibiotic treatment,
      and administration of exogenous SCFAs. The GVHD protective effect of SCFAs
      requires GPR43-mediated ERK phosphorylation and activation of the NLRP3
      inflammasome in non-hematopoietic target tissues of the host. These data provide
      insight into mechanisms of microbial metabolite-mediated protection of target
      tissues from the damage caused allogeneic T cells.

PMID- 30201972
TI  - Co-overexpression of native phospholipid-biosynthetic genes plsX and plsC
      enhances lipid production in Synechocystis sp. PCC 6803.
AB  - The overexpression of native plsX and plsC genes involving in fatty
      acid/phospholipid synthesis first timely-reported the significantly enhanced
      lipid contents in Synechocystis sp. PCC 6803. Growth rate, intracellular pigment
      contents including chlorophyll a and carotenoids, and oxygen evolution rate of
      all overexpressing (OX) strains were normally similar as wild type. For fatty
      acid compositions, saturated fatty acid, in particular palmitic acid (16:0) was
      dominantly increased in OX strains whereas slight increases of unsaturated fatty
      acids were observed, specifically linoleic acid (18:2) and alpha-linolenic acid
      (18:3). The plsC/plsX-overexpressing (OX + XC) strain produced high lipid content
      of about 24.3%w/dcw under normal condition and was further enhanced up to
      39.1%w/dcw by acetate induction. This OX + XC engineered strain was capable of
      decreasing phaA transcript level which related to poly-3-hydroxybutyrate (PHB)
      synthesis under acetate treatment. Moreover, the expression level of gene
      transcripts revealed that the plsX- and plsC/plsX-overexpression strains had also
      increased accA transcript amounts which involved in the irreversible
      carboxylation of acetyl-CoA to malonyl-CoA. Altogether, these overexpressing
      strains significantly augmented higher lipid contents when compared to wild type
      by partly overcoming the limitation of lipid production.

PMID- 30201971
TI  - ER-associated ubiquitin ligase HRD1 programs liver metabolism by targeting
      multiple metabolic enzymes.
AB  - The HMG-CoA reductase degradation protein 1 (HRD1) has been identified as a key
      enzyme for endoplasmic reticulum-associated degradation of misfolded proteins,
      but its organ-specific physiological functions remain largely undefined. Here we
      show that mice with HRD1 deletion specifically in the liver display increased
      energy expenditure and are resistant to HFD-induced obesity and liver steatosis
      and insulin resistance. Proteomic analysis identifies a HRD1 interactome, a large
      portion of which includes metabolic regulators. Loss of HRD1 results in elevated
      ENTPD5, CPT2, RMND1, and HSD17B4 protein levels and a consequent hyperactivation
      of both AMPK and AKT pathways. Genome-wide mRNA sequencing revealed that HRD1
      deficiency reprograms liver metabolic gene expression profiles, including
      suppressing genes involved in glycogenesis and lipogenesis and upregulating genes
      involved in glycolysis and fatty acid oxidation. We propose HRD1 as a liver
      metabolic regulator and a potential drug target for obesity, fatty liver disease,
      and insulin resistance associated with the metabolic syndrome.

PMID- 30201973
TI  - Relationship between perioperative thyroid function and acute kidney injury after
      thyroidectomy.
AB  - Thyroid dysfunction may alter kidney function via direct renal effects and
      systemic haemodynamic effects, but information on the effect of thyroid function
      on postoperative acute kidney injury (AKI) following thyroidectomy remains
      scarce. We reviewed the medical records of 486 patients who underwent
      thyroidectomy between January 2010 and December 2014. Thyroid function was
      evaluated based on the free thyroxine or thyroid stimulating hormone levels. The
      presence of postoperative AKI was determined using the Kidney Disease: Improving
      Global Outcomes (KDIGO) criteria. AKI developed in 24 (4.9%) patients after
      thyroidectomy. There was no association between preoperative thyroid function and
      postoperative AKI. Patients with postoperative hypothyroidism showed a higher
      incidence of AKI than patients with normal thyroid function or hyperthyroidism
      (19.4%, 6.7%, and 0%, respectively; P = 0.044). Multivariable logistic regression
      analysis showed that male sex (OR, 4.45; 95% CI, 1.80-11.82; P = 0.002),
      preoperative use of beta-blockers (OR, 4.81; 95% CI, 1.24-16.50; P = 0.016), low
      preoperative serum albumin levels (OR, 0.29; 95% CI, 0.11-0.76; P = 0.011), and
      colloid administration (OR, 5.18; 95% CI, 1.42-18.15; P = 0.011) were associated
      with postoperative AKI. Our results showed that postoperative hypothyroidism
      might increase the incidence of AKI after thyroidectomy.

PMID- 30201975
TI  - Paving the way for precision medicine v2.0 in intensive care by profiling
      necroinflammation in biofluids.
AB  - Current clinical diagnosis is typically based on a combination of approaches
      including clinical examination of the patient, clinical experience, physiologic
      and/or genetic parameters, high-tech diagnostic medical imaging, and an extended
      list of laboratory values mostly determined in biofluids such as blood and urine.
      One could consider this as precision medicine v1.0. However, recent advances in
      technology and better understanding of molecular mechanisms underlying disease
      will allow us to better characterize patients in the future. These improvements
      will enable us to distinguish patients who have similar clinical presentations
      but different cellular and molecular responses. Treatments will be able to be
      chosen more "precisely", resulting in more appropriate therapy, precision
      medicine v2.0. In this review, we will reflect on the potential added value of
      recent advances in technology and a better molecular understanding of necrosis
      and inflammation for improving diagnosis and treatment of critically ill
      patients. We give a brief overview on the mutual interplay between necrosis and
      inflammation, which are two crucial detrimental factors in organ and/or systemic
      dysfunction. One of the challenges for the future will thus be the cellular and
      molecular profiling of necroinflammation in biofluids. The huge amount of data
      generated by profiling biomolecules and single cells through, for example,
      different omic-approaches is needed for data mining methods to allow patient
      clustering and identify novel biomarkers. The real-time monitoring of biomarkers
      will allow continuous (re)evaluation of treatment strategies using machine
      learning models. Ultimately, we may be able to offer precision therapies
      specifically designed to target the molecular set-up of an individual patient, as
      has begun to be done in cancer therapeutics.

PMID- 30201974
TI  - PD-1 has a unique capacity to inhibit allergen-specific human CD4+ T cell
      responses.
AB  - T lymphocytes have a crucial role in initiating and promoting type I allergies.
      Their responses are tightly regulated by numerous activating and inhibitory
      signals provided by APCs. Here we have addressed the role of the major
      coinhibitory receptors PD-1, CTLA-4, BTLA and LAG-3 in allergen-specific CD4+ T
      cell responses. PBMCs of healthy individuals and 41 patients allergic to house
      dust mites, birch, grass or mugwort pollen were stimulated with allergenic
      extracts and expression of coinhibitory receptors on responding CD4+ T cells was
      assessed. Blocking antibodies to PD-1, CTLA-4, BTLA and LAG-3 were used to
      evaluate the role of coinhibitory pathways. Allergen-specific CD4+ T cells showed
      strong upregulation of PD-1, LAG-3 and CTLA-4 upon stimulation, whereas BTLA was
      downregulated. Blockade of PD-1 strongly enhanced proliferation and cytokine
      production (IL-10; TH1 cytokines IFN-gamma, TNF-alpha; TH2 cytokines IL-5, IL-13)
      of allergen-specific CD4+ T cells derived from allergic as well as non-allergic
      individuals. BTLA blockade enhanced proliferation but not cytokine production in
      response to house dust mite extract. Blocking LAG-3 was ineffective and
      surprisingly, we observed reduced proliferation and cytokine production in
      presence of a CTLA-4 antibody. Our results point to a unique potency of PD-1
      pathways to dampen allergen-specific human T cells.

PMID- 30201976
TI  - Highly Efficient Transfer of 7TM Membrane Protein from Native Membrane to
      Covalently Circularized Nanodisc.
AB  - Incorporating membrane proteins into membrane mimicking systems is an essential
      process for biophysical studies and structure determination. Monodisperse lipid
      nanodiscs have been found to be a suitable tool, as they provide a near-native
      lipid bilayer environment. Recently, a covalently circularized nanodisc (cND)
      assembled with a membrane scaffold protein (MSP) in circular form, instead of
      conventional linear form, has emerged. Covalently circularized nanodiscs have
      been shown to have improved stability, however the optimal strategies for the
      incorporation of membrane proteins, as well as the physicochemical properties of
      the membrane protein embedded in the cND, have not been studied.
      Bacteriorhodopsin (bR) is a seven-transmembrane helix (7TM) membrane protein, and
      it forms a two dimensional crystal consisting of trimeric bR on the purple
      membrane of halophilic archea. Here it is reported that the bR trimer in its
      active form can be directly incorporated into a cND from its native purple
      membrane. Furthermore, the assembly conditions of the native purple membrane
      nanodisc (PMND) were optimized to achieve homogeneity and high yield using a high
      sodium chloride concentration. Additionally, the native PMND was demonstrated to
      have the ability to assemble over a range of different pHs, suggesting
      flexibility in the preparation conditions. The native PMND was then found to not
      only preserve the trimeric structure of bR and most of the native lipids in the
      PM, but also maintained the photocycle function of bR. This suggests a promising
      potential for assembling a cND with a 7TM membrane protein, extracted directly
      from its native membrane environment, while preserving the protein conformation
      and lipid composition.

PMID- 30201977
TI  - The first crystal structure of a DNA-free nuclear receptor DNA binding domain
      sheds light on DNA-driven allostery in the glucocorticoid receptor.
AB  - The glucocorticoid receptor (GR) is a steroid hormone receptor of the nuclear
      receptor family that regulates gene expression in response to glucocorticoid
      hormone signaling. Interaction with specific GR DNA binding sequences causes
      conformational changes in the GR DNA binding domain (DBD) that result in
      recruitment of specific sets of co-regulators that determine transcriptional
      outcomes. We have solved the crystal structure of GR DBD in its DNA-free state,
      the first such crystal structure from any nuclear receptor. In contrast to
      previous NMR structures, this crystal structure reveals that free GR DBD adopts a
      conformation very similar to DNA-bound states. The lever arm region is the most
      variable element in the free GR DBD. Molecular dynamics of the free GR DBD as
      well as GR DBD bound to activating and repressive DNA elements confirm lever arm
      flexibility in all functional states. Cluster analysis of lever arm conformations
      during simulations shows that DNA binding and dimerization cause a reduction in
      the number of conformations sampled by the lever arm. These results reveal that
      DNA binding and dimerization drive conformational selection in the GR DBD lever
      arm region and show how DNA allosterically controls GR structure and dynamics.

PMID- 30201978
TI  - Genetic dissection of grain zinc concentration in spring wheat for mainstreaming
      biofortification in CIMMYT wheat breeding.
AB  - Wheat is an important staple that acts as a primary source of dietary energy,
      protein, and essential micronutrients such as iron (Fe) and zinc (Zn) for the
      world's population. Approximately two billion people suffer from micronutrient
      deficiency, thus breeders have crossed high Zn progenitors such as synthetic
      hexaploid wheat, T. dicoccum, T. spelta, and landraces to generate wheat
      varieties with competitive yield and enhanced grain Zn that are being adopted by
      farmers in South Asia. Here we report a genome-wide association study (GWAS)
      using the wheat Illumina iSelect 90 K Infinitum SNP array to characterize grain
      Zn concentrations in 330 bread wheat lines. Grain Zn phenotype of this
      HarvestPlus Association Mapping (HPAM) panel was evaluated across a range of
      environments in India and Mexico. GWAS analysis revealed 39 marker-trait
      associations for grain Zn. Two larger effect QTL regions were found on
      chromosomes 2 and 7. Candidate genes (among them zinc finger motif of
      transcription-factors and metal-ion binding genes) were associated with the QTL.
      The linked markers and associated candidate genes identified in this study are
      being validated in new biparental mapping populations for marker-assisted
      breeding.

PMID- 30201979
TI  - Ectopic expression of aPKC-mediated phosphorylation in p300 modulates hippocampal
      neurogenesis, CREB binding and fear memory differently with age.
AB  - Epigenetic modifications have become an emerging interface that links extrinsic
      signals to alterations of gene expression that determine cell identity and
      function. However, direct signaling that regulates epigenetic modifications is
      unknown. Our previous work demonstrated that phosphorylation of CBP at Ser 436 by
      atypical protein kinase C (aPKC) regulates age-dependent hippocampal neurogenesis
      and memory. p300, a close family member of CBP, lacks the aPKC-mediated
      phosphorylation found in CBP. Here, we use a phosphorylation-competent p300
      (G442S) knock-in (KI) mouse model that ectopically expresses p300 phosphorylation
      in a homologous site to CBP Ser436, and assess its roles in modulating
      hippocampal neurogenesis, CREB binding ability, and fear memory. Young adult (3
      months) p300G422S-KI mice exhibit enhanced hippocampal neurogenesis due to
      increased cell survival of newly-generated neurons, without alterations in CREB
      binding and contextual fear memory. On the other hand, mature adult (6 months)
      p300G422S-KI mice display reduced CREB binding, associated with impaired
      contextual fear memory without alterations in hippocampal neurogenesis.
      Additionally, we show that repulsive interaction between pS133-CREB and pS422
      p300G422S may contribute to the reduced CREB binding to p300G422S. Together,
      these data suggest that a single phosphorylation change in p300 has the
      capability to modulate hippocampal neurogenesis, CREB binding, and associative
      fear memory.

PMID- 30201981
TI  - Breath acetone as a marker of energy balance: an exploratory study in healthy
      humans.
AB  - An exploratory study was performed on eight healthy volunteers to assess how
      short-term changes in energy balance and dietary carbohydrate content impact
      breath acetone concentrations. Participants were studied on three occasions: on
      each occasion, they remained fasted and in resting conditions during the first 2
      h to assess basal breath acetone and blood beta-hydroxybutyrate (BOHB). During
      the next 6 h, they remained fasted on one occasion (F), or were fed hourly high
      carbohydrate (HC) or low-carbohydrate (LC) meals to induce a positive energy
      balance on the other two occasions. They remained in resting conditions during 4
      h, then performed a 2-hour low intensity exercise (25 W) inducing a negative
      energy balance. In resting conditions, breath acetone and blood BOHB
      concentrations increased progressively compared to basal values in F, but
      decreased and remained low throughout the test in HC. With LC, breath acetone
      increased progressively, while blood BOHB decreased. This exploratory study
      indicates that breath acetone reliably detects a stimulation of ketogenesis
      during a short-term fast. It also suggests that LC and HC differentially impact
      BOHB and acetone production and utilization, and reveals possible limitations to
      the use of breath acetone as a marker of energy balance.

PMID- 30201980
TI  - Platelet activation and prothrombotic properties in a mouse model of peritoneal
      sepsis.
AB  - Sepsis is associated with thrombocytopenia and microvascular thrombosis. Studies
      have described platelets implication in this pathology but their kinetics of
      activation and behavior remain poorly known. We show in a mouse model of
      peritonitis, the appearance of platelet-rich thrombi in organ microvessels and
      organ damage. Complementary methods are necessary to characterize platelet
      activation during sepsis as circulating soluble markers and platelet-monocyte
      aggregates revealed early platelet activation, while surface activation markers
      were detected at later stage. A microfluidic based ex-vivo thrombosis assay
      demonstrated that platelets from septic mice have a prothrombotic behavior at
      shear rate encountered in microvessels. Interestingly, we found that even though
      phosphoinositide-3-kinase beta-deficient platelet mice formed less thrombi in
      liver microcirculation, peritoneal sepsis activates a platelet alternative
      pathway to compensate the otherwise mandatory role of this lipid-kinase to form
      stable thrombi at high shear rate. Platelets are rapidly activated during sepsis.
      Thrombocytopenia can be attributed in part to platelet-rich thrombi formation in
      capillaries and platelet-leukocytes interactions. Platelets from septic mice have
      a prothrombotic phenotype at a shear rate encountered in arterioles. Further
      studies are necessary to unravel molecular mechanisms leading to this
      prothrombotic state of platelets in order to guide the development of future
      treatments of polymicrobial sepsis.

PMID- 30201982
TI  - Super-silent FRET Sensor Enables Live Cell Imaging and Flow Cytometric
      Stratification of Intracellular Serine Protease Activity in Neutrophils.
AB  - Serine proteases are released by neutrophils to act primarily as antimicrobial
      proteins but excessive and unbalanced serine protease activity results in serious
      host tissue damage. Here the synthesis of a novel chemical sensor based on a
      multi-branched fluorescence quencher is reported. It is super-silent, exhibiting
      no fluorescence until de-quenched by the exemplar serine protease human
      neutrophil elastase, rapidly enters human neutrophils, and is inhibited by serine
      protease inhibitors. This sensor allows live imaging of intracellular serine
      protease activity within human neutrophils and demonstrates that the unique
      combination of a multivalent scaffold combined with a FRET peptide represents a
      novel and efficient strategy to generate super-silent sensors that permit the
      visualisation of intracellular proteases and may enable point of care whole blood
      profiling of neutrophils.

PMID- 30201984
TI  - Cardiovascular events in chronic myeloid leukemia clinical trials. Is it time to
      reassess and report the events according to cardiology guidelines?
AB  - Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of chronic
      myeloid leukemia (CML). Although these treatments have changed the natural course
      of CML and many other cancers, they may cause cardiovascular and/or metabolic
      complications. In this review, we discuss how overlooking the main drivers of
      cardiovascular events (CVEs) and lack of standard definitions for cardiovascular
      adverse events might have affected these event rates in CML trials.
      Methodological limitations that affect the available data are discussed, with an
      emphasis on the future direction of cardiovascular safety research in trials of
      investigational drugs in cancer treatment.

PMID- 30201985
TI  - Risk of MGUS in relatives of multiple myeloma cases by clinical and tumor
      characteristics.
AB  - We and others have shown increased risk of monoclonal gammopathy of undetermined
      significance (MGUS) in first-degree relatives of patients with multiple myeloma
      (MM). Whether familial risk of MGUS differs by the MM proband's age at onset,
      tumor or clinical characteristics is unknown. MM and smoldering MM (SMM) cases (N
      = 430) were recruited from the Mayo Clinic in Rochester, Minnesota between 2005
      2015. First-degree relatives over age 40 provided serum samples for evaluation of
      MGUS (N = 1179). Age and sex specific rates of MGUS among first-degree relatives
      were compared to a population-based sample. Cytogenetic subtypes were classified
      by Fluorescence in situ hybridization. MGUS was detected in 75 first-degree
      relatives for an age- and sex- adjusted prevalence of 5.8% (95% CI: 4.5-7.2).
      Prevalence of MGUS in first-degree relatives was 2.4 fold (95% CI: 1.9-2.9)
      greater than expected rates. Familial risk did not differ by proband's age at
      diagnosis, gender, isotype, IgH translocation, or trisomy. This study confirms
      first-degree relatives of MM cases have a significantly higher risk of MGUS
      compared to the general population, regardless of age, gender, or tumor
      characteristics. In selected situations, such as multiple affected first-degree
      relatives, screening of first-degree relatives of MM cases could be considered
      for follow-up and prevention strategies.

PMID- 30201983
TI  - NT5C2 germline variants alter thiopurine metabolism and are associated with
      acquired NT5C2 relapse mutations in childhood acute lymphoblastic leukaemia.
AB  - The antileukaemic drug 6-mercaptopurine is converted into thioguanine nucleotides
      (TGN) and incorporated into DNA (DNA-TG), the active end metabolite. In a series
      of genome-wide association studies, we analysed time-weighted means (wm) of
      erythrocyte concentrations of TGN (Ery-TGN) and DNA-TG in 1009 patients
      undergoing maintenance therapy for acute lymphoblastic leukaemia (ALL). In
      discovery analyses (454 patients), the propensity for DNA-TG incorporation (wmDNA
      TG/wmEry-TGN ratio) was significantly associated with three intronic SNPs in
      NT5C2 (top hit: rs72846714; P = 2.09 * 10-10, minor allele frequency 15%). In
      validation analyses (555 patients), this association remained significant during
      both early and late maintenance therapy (P = 8.4 * 10-6 and 1.3 * 10-3,
      respectively). The association was mostly driven by differences in wmEry-TGN, but
      in regression analyses adjusted for wmEry-TGN (P < 0.0001), rs72846714-A genotype
      was also associated with a higher wmDNA-TG (P = 0.029). Targeted sequencing of
      NT5C2 did not identify any missense variants associated with rs72846714 or wmEry
      TGN/wmDNA-TG. rs72846714 was not associated with relapse risk, but in a separate
      cohort of 180 children with relapsed ALL, rs72846714-A genotype was associated
      with increased occurrence of relapse-specific NT5C2 gain-of-function mutations
      that reduce cytosol TGN levels (P = 0.03). These observations highlight the
      impact of both germline and acquired mutations in drug metabolism and disease
      trajectory.

PMID- 30201986
TI  - SMRT-Cappable-seq reveals complex operon variants in bacteria.
AB  - Current methods for genome-wide analysis of gene expression require fragmentation
      of original transcripts into small fragments for short-read sequencing. In
      bacteria, the resulting fragmented information hides operon complexity.
      Additionally, in vivo processing of transcripts confounds the accurate
      identification of the 5' and 3' ends of operons. Here we develop a methodology
      called SMRT-Cappable-seq that combines the isolation of un-fragmented primary
      transcripts with single-molecule long read sequencing. Applied to E. coli, this
      technology results in an accurate definition of the transcriptome with 34% of
      known operons from RegulonDB being extended by at least one gene. Furthermore,
      40% of transcription termination sites have read-through that alters the gene
      content of the operons. As a result, most of the bacterial genes are present in
      multiple operon variants reminiscent of eukaryotic splicing. By providing such
      granularity in the operon structure, this study represents an important resource
      for the study of prokaryotic gene network and regulation.

PMID- 30201987
TI  - Big brown bats (Eptesicus fuscus) successfully navigate through clutter after
      exposure to intense band-limited sound.
AB  - Echolocating big brown bats fly, orient, forage, and roost in cluttered acoustic
      environments in which aggregate sound pressure levels can be as intense as 100 to
      140 dB SPL, levels that would impair auditory perception in other terrestrial
      mammals. We showed previously that bats exposed to intense wide-band sound (116
      dB SPL) can navigate successfully through dense acoustic clutter. Here, we extend
      these results by quantifying performance of bats navigating through a cluttered
      scene after exposure to intense band-limited sounds (bandwidths 5-25 kHz, 123 dB
      SPL). Behavioral performance was not significantly affected by prior sound
      exposure, with the exception of one bat after exposure to one sound. Even in this
      outlying case, performance recovered rapidly, by 10 min post-exposure. Temporal
      patterning of biosonar emissions during successful flights showed that bats
      maintained their individual strategies for navigating through the cluttered scene
      before and after exposures. In unsuccessful flights, interpulse intervals were
      skewed towards shorter values, suggesting a shift in strategy for solving the
      task rather than a hearing impairment. Results confirm previous findings that big
      brown bats are not as susceptible to noise-induced perceptual impairments as are
      other terrestrial mammals exposed to sounds of similar intensity and bandwidth.

PMID- 30201989
TI  - Electrical tuning of elastic wave propagation in nanomechanical lattices at MHz
      frequencies.
AB  - Nanoelectromechanical systems (NEMS) that operate in the megahertz (MHz) regime
      allow energy transducibility between different physical domains. For example,
      they convert optical or electrical signals into mechanical motions and vice
      versa1. This coupling of different physical quantities leads to frequency-tunable
      NEMS resonators via electromechanical non-linearities2-4. NEMS platforms with
      single- or low-degrees of freedom have been employed to demonstrate quantum-like
      effects, such as mode cooling5, mechanically induced transparency5, Rabi
      oscillation6,7, two-mode squeezing8 and phonon lasing9. Periodic arrays of NEMS
      resonators with architected unit cells enable fundamental studies of lattice
      based solid-state phenomena, such as bandgaps10,11, energy transport10-12, non
      linear dynamics and localization13,14, and topological properties15, directly
      transferrable to on-chip devices. Here we describe one-dimensional, non-linear,
      nanoelectromechanical lattices (NEML) with active control of the frequency band
      dispersion in the radio-frequency domain (10-30 MHz). The design of our systems
      is inspired by NEMS-based phonon waveguides10,11 and includes the voltage-induced
      frequency tuning of the individual resonators2-4. Our NEMLs consist of a periodic
      arrangement of mechanically coupled, free-standing nanomembranes with circular
      clamped boundaries. This design forms a flexural phononic crystal with a well
      defined bandgap, 1.8 MHz wide. The application of a d.c. gate voltage creates
      voltage-dependent on-site potentials, which can significantly shift the frequency
      bands of the device. Additionally, a dynamic modulation of the voltage triggers
      non-linear effects, which induce the formation of a phononic bandgap in the
      acoustic branch, analogous to Peierls transition in condensed matter16. The
      gating approach employed here makes the devices more compact than recently
      proposed systems, whose tunability mostly relies on materials' compliance17,18
      and mechanical non-linearities19-22.

PMID- 30201990
TI  - Electrical half-wave rectification at ferroelectric domain walls.
AB  - Domain walls in ferroelectric semiconductors show promise as multifunctional two
      dimensional elements for next-generation nanotechnology. Electric fields, for
      example, can control the direct-current resistance and reversibly switch between
      insulating and conductive domain-wall states, enabling elementary electronic
      devices such as gates and transistors. To facilitate electrical signal processing
      and transformation at the domain-wall level, however, an expansion into the realm
      of alternating-current technology is required. Here, we demonstrate diode-like
      alternating-to-direct current conversion based on neutral ferroelectric domain
      walls in ErMnO3. By combining scanning probe and dielectric spectroscopy, we show
      that the rectification occurs at the tip-wall contact for frequencies at which
      the walls are effectively pinned. Using density functional theory, we attribute
      the responsible transport behaviour at the neutral walls to an accumulation of
      oxygen defects. The practical frequency regime and magnitude of the direct
      current output are controlled by the bulk conductivity, establishing electrode
      wall junctions as versatile atomic-scale diodes.

PMID- 30201988
TI  - New Optical Imaging Reporter-labeled Anaplastic Thyroid Cancer-Derived
      Extracellular Vesicles as a Platform for In Vivo Tumor Targeting in a Mouse
      Model.
AB  - Extracellular vesicles (EVs), originating from multivesicular bodies by
      invagination of the endosomal membrane, are communication channels between
      distant cells. They are natural carriers of exogeneous cellular materials and
      have been exploited as drug delivery carriers in various diseases. Here, we found
      that tumor cell-derived EVs can be used as efficient targets in tumors by
      monitoring with an optical reporter system. Anaplastic thyroid cancer (CAL62)
      cell-derived EVs with Renilla luciferase (Rluc) were used to target CAL62 tumors
      in a mouse model. Optical imaging revealed that cancer cell-derived EVs (EV
      CAL62/Rluc) targeted the original tumor (CAL62) in mice within 30 min after
      systemic injection. Furthermore, fluorescence imaging revealed that EV-CAL62/Rluc
      were internalized into CAL62 tumors in the mice. Ex vivo Optical imaging further
      confirmed the in vivo finding. Here, we successfully monitored the tumor
      targeting ability of tumor cell-derived EVs by optical imaging. Based on these
      results, tumor cell-derived EVs are highly effective natural carriers for drug
      delivery for cancer therapies.

PMID- 30201991
TI  - An immunoregulatory and tissue-residency program modulated by c-MAF in human TH17
      cells.
AB  - Different types of effector and memory T lymphocytes are induced and maintained
      in protective or pathological immune responses. Here we characterized two human
      CD4+ TH17 helper cell subsets that, in the recently activated state, could be
      distinguished on the basis of their expression of the anti-inflammatory cytokine
      IL-10. IL-10+ TH17 cells upregulated a variety of genes encoding immunoregulatory
      molecules, as well as genes whose expression is characteristic of tissue-resident
      T cells. In contrast, IL-10- TH17 cells maintained a pro-inflammatory gene
      expression profile and upregulated the expression of homing receptors that guide
      recirculation from tissues to blood. Expression of the transcription factor c-MAF
      was selectively upregulated in IL-10+ TH17 cells, and it was bound to a large set
      of enhancer-like regions and modulated the immunoregulatory and tissue-residency
      program. Our results identify c-MAF as a relevant factor that drives two highly
      divergent post-activation fates of human TH17 cells and provide a framework with
      which to investigate the role of these cells in physiology and immunopathology.

PMID- 30201993
TI  - Mysterious ILC2 tissue adaptation.

PMID- 30201992
TI  - Tissue signals imprint ILC2 identity with anticipatory function.
AB  - Group 2 innate lymphoid cells (ILC2s) are distributed systemically and produce
      type 2 cytokines in response to a variety of stimuli, including the epithelial
      cytokines interleukin (IL)-25, IL-33, and thymic stromal lymphopoietin (TSLP).
      Transcriptional profiling of ILC2s from different tissues, however, grouped ILC2s
      according to their tissue of origin, even in the setting of combined IL-25-, IL
      33-receptor-, and TSLP-receptor-deficiency. Single-cell profiling confirmed a
      tissue-organizing transcriptome and identified ILC2 subsets expressing distinct
      activating receptors, including the major subset of skin ILC2s, which were
      activated preferentially by IL-18. Tissue ILC2 subsets were unaltered in number
      and expression in germ-free mice, suggesting that endogenous, tissue-derived
      signals drive the maturation of ILC2 subsets by controlling expression of
      distinct patterns of activating receptors, thus anticipating tissue-specific
      perturbations occurring later in life.

PMID- 30201994
TI  - Combating herpesvirus encephalitis by potentiating a TLR3-mTORC2 axis.
AB  - TLR3 is a sensor of double-stranded RNA that is indispensable for defense against
      infection with herpes simplex virus type 1 (HSV-1) in the brain. We found here
      that TLR3 was required for innate immune responses to HSV-1 in neurons and
      astrocytes. During infection with HSV-1, TLR3 recruited the metabolic checkpoint
      kinase complex mTORC2, which led to the induction of chemokines and trafficking
      of TLR3 to the cell periphery. Such trafficking enabled the activation of
      molecules (including mTORC1) required for the induction of type I interferons.
      Intracranial infection of mice with HSV-1 was exacerbated by impairment of TLR3
      responses with an inhibitor of mTOR and was significantly 'rescued' by
      potentiation of TLR3 responses with an agonistic antibody to TLR3. These results
      suggest that the TLR3-mTORC2 axis might be a therapeutic target through which to
      combat herpes simplex encephalitis.

PMID- 30201995
TI  - Multisensory and Motor Representations in Rat Oral Somatosensory Cortex.
AB  - In mammals, a complex array of oral sensors assess the taste, temperature and
      haptic properties of food. Although the representation of taste has been
      extensively studied in the gustatory cortex, it is unclear how the somatosensory
      cortex encodes information about the properties of oral stimuli. Moreover, it is
      poorly understood how different oral sensory modalities are integrated and how
      sensory responses are translated into oral motor actions. To investigate whether
      oral somatosensory cortex processes food-related sensations and movements, we
      performed in vivo whole-cell recordings and motor mapping experiments in rats.
      Neurons in oral somatosensory cortex showed robust post-synaptic and sparse
      action potential responses to air puffs. Membrane potential showed that cold
      water evoked larger responses than room temperature or hot water. Most neurons
      showed no clear tuning of responses to bitter, sweet and neutral gustatory
      stimuli. Finally, motor mapping experiments with histological verification
      revealed an initiation of movements related to food consumption behavior, such as
      jaw opening and tongue protrusions. We conclude that somatosensory cortex: (i)
      provides a representation of the temperature of oral stimuli, (ii) does not
      systematically encode taste information and (iii) influences orofacial movements
      related to food consummatory behavior.

PMID- 30201998
TI  - Transportation mode and timing of spinal cord decompression and stabilization in
      patients with traumatic spinal cord injury in Iran.
AB  - STUDY DESIGN: Cross-sectional retrospective study. OBJECTIVE: To describe the
      transportation mode to hospital and timing of spinal cord decompression and
      stabilization (D&S), length of hospital stay, frequency of pressure injuries, and
      sepsis during hospitalization. SETTING: Brain and Spinal Injury Research Center,
      Tehran, Iran. METHODS: Eight hundred and thirty patients with traumatic spinal
      cord injury (TSCI) were enrolled. Mode of transportation and length of time to
      reach the first hospital, length of hospital stay (LOS), and the time span
      between hospital arrival and decompression and stabilization (D&S) were recorded.
      RESULTS: Fifty-nine percent of the enrolled individuals were transported to the
      first hospital by ambulance, while 41% were transferred by vehicles without
      medical equipment and personnel. Median length of time to reach the first
      hospital was 1 h for both ambulance and non-equipped car groups, with no
      statistically significant difference (p = 0.1). Median LOS, frequencies of
      pressure injuries, and sepsis based on the injury levels were not significantly
      different between two transportation modalities. One hundred and seventy-seven
      individuals had early surgery, and 254 had late surgery. Median LOS was 13 days
      in the early surgery group and 20 days in the late surgery group (p = 0.002).
      Frequencies of pressure injuries and sepsis were not significantly different
      between the late and early surgery groups for various injury levels. CONCLUSION:
      About 59% of our patients had been transported to a hospital by non-medical
      personnel. Those with late surgery had significantly longer LOS. Improving TSCI
      patients' transportation method and early surgical interventions, if possible,
      may be considered.

PMID- 30201996
TI  - Entanglement and teleportation between polarization and wave-like encodings of an
      optical qubit.
AB  - Light is an irreplaceable means of communication among various quantum
      information processing and storage devices. Due to their different physical
      nature, some of these devices couple more strongly to discrete, and some to
      continuous degrees of freedom of a quantum optical wave. It is therefore
      desirable to develop a technological capability to interconvert quantum
      information encoded in these degrees of freedom. Here we generate and
      characterize an entangled state between a dual-rail (polarization-encoded) single
      photon qubit and a qubit encoded as a superposition of opposite-amplitude
      coherent states. We furthermore demonstrate the application of this state as a
      resource for the interfacing of quantum information between these encodings. In
      particular, we show teleportation of a polarization qubit onto a freely
      propagating continuous-variable qubit.

PMID- 30201997
TI  - Combined small RNA and gene expression analysis revealed roles of miRNAs in maize
      response to rice black-streaked dwarf virus infection.
AB  - Maize rough dwarf disease, caused by rice black-streaked dwarf virus (RBSDV), is
      a devastating disease in maize (Zea mays L.). MicroRNAs (miRNAs) are known to
      play critical roles in regulation of plant growth, development, and adaptation to
      abiotic and biotic stresses. To elucidate the roles of miRNAs in the regulation
      of maize in response to RBSDV, we employed high-throughput sequencing technology
      to analyze the miRNAome and transcriptome following RBSDV infection. A total of
      76 known miRNAs, 226 potential novel miRNAs and 351 target genes were identified.
      Our dataset showed that the expression patterns of 81 miRNAs changed dramatically
      in response to RBSDV infection. Transcriptome analysis showed that 453 genes were
      differentially expressed after RBSDV infection. GO, COG and KEGG analysis results
      demonstrated that genes involved with photosynthesis and metabolism were
      significantly enriched. In addition, twelve miRNA-mRNA interaction pairs were
      identified, and six of them were likely to play significant roles in maize
      response to RBSDV. This study provided valuable information for understanding the
      molecular mechanism of maize disease resistance, and could be useful in method
      development to protect maize against RBSDV.

PMID- 30201999
TI  - Deglacial mobilization of pre-aged terrestrial carbon from degrading permafrost.
AB  - The mobilization of glacial permafrost carbon during the last glacial
      interglacial transition has been suggested by indirect evidence to be an
      additional and significant source of greenhouse gases to the atmosphere,
      especially at times of rapid sea-level rise. Here we present the first direct
      evidence for the release of ancient carbon from degrading permafrost in East Asia
      during the last 17 kyrs, using biomarkers and radiocarbon dating of terrigenous
      material found in two sediment cores from the Okhotsk Sea. Upscaling our results
      to the whole Arctic shelf area, we show by carbon cycle simulations that
      deglacial permafrost-carbon release through sea-level rise likely contributed
      significantly to the changes in atmospheric CO2 around 14.6 and 11.5 kyrs BP.

PMID- 30202000
TI  - Transferrin as a thermosensitizer in radiofrequency hyperthermia for cancer
      treatment.
AB  - One of the main characteristics of cancer tissues is poor development of
      neovascularization that results in a limited blood circulation. Because of this
      phenomenon, it is harder for cancer tissues to diffuse their elevated heat into
      other parts of the body. The scientific principle of radiofrequency hyperthermia
      relies on this quality of cancer tissues which with higher temperature becomes
      more apparent. Despite the obvious necessity to selectively heat the cancer
      tissue for radiofrequency hyperthermia, a proper thermosensitizer has not been
      developed until now. Here, we show that transferrin containing ferric ion could
      be an ideal thermosensitizer for the increased efficiency of radiofrequency
      hyperthermia. In our result, the ferric ion-enriched cancer tissues dramatically
      react with 13.56 MHz radiofrequency wave to cause cancer-selective dielectric
      temperature increment. The overall anticancer efficacy of a 13.56 MHz
      radiofrequency hyperthermia using transferrin as a thermosensitizer was much
      higher than the oncotherapeutic efficacy of paclitaxel, successfully eradicating
      cancer in a tumor-xenografted mouse experiment.

PMID- 30202001
TI  - Automatic analysis algorithm for acquiring standard dental and mandibular shape
      data using cone-beam computed tomography.
AB  - This study aims to introduce a new algorithm developed using retrospective cone
      beam computed tomography (CBCT) data to obtain a standard dental and mandibular
      arch shape automatically for an optimal panoramic focal trough. A custom-made
      program was developed to analyze each arch shape of randomly collected 30 CBCT
      images. First, volumetric data of the mandible were binarized and projected in
      the axial direction to obtain 2-dimensional arch images. Second, 30 patients'
      mandibular arches were superimposed on the center of the bilateral distal contact
      points of the mandibular canines to generate an average arch shape. Third, the
      center and boundary of a panoramic focal trough were obtained using smoothing
      splines. As a result, the minimum thickness and transition of the focal trough
      could be obtained. If this new algorithm is applied to big data of retrospective
      CBCT images, standard focal troughs could be established by race, sex, and age
      group, which would improve the image quality of dental panoramic radiography.

PMID- 30202002
TI  - Exploring the elusive composition of corpora amylacea of human brain.
AB  - Corpora amylacea (CA) are polyglucosan bodies that accumulate in the human brain
      during ageing and are also present in large numbers in neurodegenerative
      conditions. Theories regarding the function of CA are regularly updated as new
      components are described. In previous work, we revealed the presence of some neo
      epitopes in CA and the existence of some natural IgM antibodies directed against
      these neo-epitopes. We also noted that these neo-epitopes and IgMs were the cause
      of false staining in CA immunohistochemical studies, and disproved the proposed
      presence of beta-amyloid peptides and tau protein in them. Here we extend the
      list of components erroneously attributed to CA. We show that, contrary to
      previous descriptions, CA do not contain GFAP, S100, AQP4, NeuN or class III beta
      tubulin, and we question the presence of other components. Nonetheless, we
      observe that CA contains ubiquitin and p62, both of them associated with
      processes of elimination of waste substances, and also glycogen synthase, an
      indispensable enzyme for polyglucosan formation. In summary, this study shows
      that it is imperative to continue reviewing previous studies about CA but, more
      importantly, it shows that the vision of CA as structures involved in protective
      or cleaning mechanisms remains the most consistent theory.

PMID- 30202003
TI  - Advanced fabrication of biosensor on detection of Glypican-1 using S
      Acetylmercaptosuccinic anhydride (SAMSA) modification of antibody.
AB  - Glypican-1 (GPC-1) has been recognized as biomarker of pancreatic cancer.
      Quantification of GPC-1 level is also pivotal to breast cancer and prostate
      cancer's patients. We hereby report the first biosensor for GPC-1 detection.
      Instead of using crosslinking technique and surface immobilization of antibody,
      we applied a novel method for biosensor fabrication, using S
      Acetylmercaptosuccinic anhydride (SAMSA) to modify the Anti-GPC-1 producing a
      thiol-linked Anti-GPC-1. The thiol-linked Anti-GPC-1 was then directly formed a
      single-layer antibody layer on the gold biosensor, minimizing the biosensor
      preparation steps significantly. Time of Flight Secondary Ions Mass Spectroscopy
      (TOF-SIMS) characterization verified the thiol-linked antibody layer and
      demonstrated a unique perspective for surface protein characterization.
      Differential pulse voltammetry (DPV) was applied to quantify GPC-1 antigen in
      undiluted human serum with a concentration range of 5,000 pg/uL to 100 pg/uL. The
      performance of this newly designed biosensor was also compared with modified self
      assembled monolayer system fabricated biosensor, demonstrating the high
      sensitivity and high-reproducibility of the SAMSA modified antibody based
      biosensor. This simple fabrication method can also expand to detection of other
      biomolecules. The simplified operation process shows great potential in clinical
      application development.

PMID- 30202005
TI  - Effective passivation of Ag nanowire network by transparent tetrahedral amorphous
      carbon film for flexible and transparent thin film heaters.
AB  - We developed effective passivation method of flexible Ag nanowire (NW) network
      electrodes using transparent tetrahedral amorphous carbon (ta-C) film prepared by
      filtered cathode vacuum arc (FCVA) coating. Even at room temperature process of
      FCVA, the ta-C passivation layer effectively protect Ag NW network electrode and
      improved the ambient stability of Ag NW network without change of sheet
      resistance of Ag NW network. In addition, ta-C coated Ag NW electrode showed
      identical critical inner and outer bending radius to bare Ag NW due to the thin
      thickness of ta-C passivation layer. The time-temperature profiles demonstrate
      that the performance of the transparent and flexible thin film heater (TFH) with
      the ta-C/Ag NW network is better than that of a TFH with Ag NW electrodes due to
      thermal stability of FCVA grown ta-C layer. In addition, the transparent and
      flexible TFHs with ta-C/Ag NW showed robustness against external force due to its
      high hardness and wear resistance. This indicates that the FCVA coated ta-C is
      promising passivation and protective layer for chemically weak Ag NW network
      electrodes against sulfur in ambient.

PMID- 30202004
TI  - Conserved collateral antibiotic susceptibility networks in diverse clinical
      strains of Escherichia coli.
AB  - There is urgent need to develop novel treatment strategies to reduce
      antimicrobial resistance. Collateral sensitivity (CS), where resistance to one
      antimicrobial increases susceptibility to other drugs, might enable selection
      against resistance during treatment. However, the success of this approach would
      depend on the conservation of CS networks across genetically diverse bacterial
      strains. Here, we examine CS conservation across diverse Escherichia coli strains
      isolated from urinary tract infections. We determine collateral susceptibilities
      of mutants resistant to relevant antimicrobials against 16 antibiotics.
      Multivariate statistical analyses show that resistance mechanisms, in particular
      efflux-related mutations, as well as the relative fitness of resistant strains,
      are principal contributors to collateral responses. Moreover, collateral
      responses shift the mutant selection window, suggesting that CS-informed
      therapies may affect evolutionary trajectories of antimicrobial resistance. Our
      data allow optimism for CS-informed therapy and further suggest that rapid
      detection of resistance mechanisms is important to accurately predict collateral
      responses.

PMID- 30202006
TI  - A fully protected hydrogenase/polymer-based bioanode for high-performance
      hydrogen/glucose biofuel cells.
AB  - Hydrogenases with Ni- and/or Fe-based active sites are highly active hydrogen
      oxidation catalysts with activities similar to those of noble metal catalysts.
      However, the activity is connected to a sensitivity towards high-potential
      deactivation and oxygen damage. Here we report a fully protected polymer
      multilayer/hydrogenase-based bioanode in which the sensitive hydrogen oxidation
      catalyst is protected from high-potential deactivation and from oxygen damage by
      using a polymer multilayer architecture. The active catalyst is embedded in a low
      potential polymer (protection from high-potential deactivation) and covered with
      a polymer-supported bienzymatic oxygen removal system. In contrast to previously
      reported polymer-based protection systems, the proposed strategy fully decouples
      the hydrogenase reaction form the protection process. Incorporation of the
      bioanode into a hydrogen/glucose biofuel cell provides a benchmark open circuit
      voltage of 1.15 V and power densities of up to 530 uW cm-2 at 0.85 V.

PMID- 30202007
TI  - CXCL12 and MYC control energy metabolism to support adaptive responses after
      kidney injury.
AB  - Kidney injury is a common complication of severe disease. Here, we report that
      injuries of the zebrafish embryonal kidney are rapidly repaired by a migratory
      response in 2-, but not in 1-day-old embryos. Gene expression profiles between
      these two developmental stages identify cxcl12a and myca as candidates involved
      in the repair process. Zebrafish embryos with cxcl12a, cxcr4b, or myca deficiency
      display repair abnormalities, confirming their role in response to injury. In
      mice with a kidney-specific knockout, Cxcl12 and Myc gene deletions suppress
      mitochondrial metabolism and glycolysis, and delay the recovery after
      ischemia/reperfusion injury. Probing these observations in zebrafish reveal that
      inhibition of glycolysis slows fast migrating cells and delays the repair after
      injury, but does not affect the slow cell movements during kidney development.
      Our findings demonstrate that Cxcl12 and Myc facilitate glycolysis to promote
      fast migratory responses during development and repair, and potentially also
      during tumor invasion and metastasis.

PMID- 30202010
TI  - Reconstruction of the cropland cover changes in eastern China between the 10th
      century and 13th century using historical documents.
AB  - To evaluate and improve datasets of anthropogenic land cover change used in local
      and global climate models, great efforts were made to reconstruct historical land
      use, including the LandCover 6k project which dedicated to reconstructing human
      land use over the past 10,000 years. In this study, we utilized historical
      records, including taxed-cropland and cropland measurement areas, and data on the
      number of households in eastern China between the 10th century and 13th century
      in concert with coefficient calibration, model allocation, and per capita
      cropland estimation to reconstruct areas of provincial cropland for 22 provinces
      over five time periods. Our reconstructions indicate that total cropland areas of
      eastern China for AD 1000, 1066, 1078, 1162, and 1215 are 34.74 * 106 ha, 49.42 *
      106 ha, 51.62 * 106 ha, 35.21 * 106 ha, and 51.21 * 106 ha, respectively. And the
      cropland area fluctuated because of dynasty shift and went through three phases.
      Cropland expansion and contraction mainly occurred in the middle and lower
      reaches of the Yangtze and Yellow Rivers as well as the Huaihe River Basin, while
      in some regions far away from battlefields, including northeastern and southern
      China, cropland area expanded continuously throughout the study period.

PMID- 30202008
TI  - Contribution of allelic imbalance to colorectal cancer.
AB  - Point mutations in cancer have been extensively studied but chromosomal gains and
      losses have been more challenging to interpret due to their unspecific nature.
      Here we examine high-resolution allelic imbalance (AI) landscape in 1699
      colorectal cancers, 256 of which have been whole-genome sequenced (WGSed). The
      imbalances pinpoint 38 genes as plausible AI targets based on previous knowledge.
      Unbiased CRISPR-Cas9 knockout and activation screens identified in total 79 genes
      within AI peaks regulating cell growth. Genetic and functional data implicate
      loss of TP53 as a sufficient driver of AI. The WGS highlights an influence of
      copy number aberrations on the rate of detected somatic point mutations.
      Importantly, the data reveal several associations between AI target genes,
      suggesting a role for a network of lineage-determining transcription factors in
      colorectal tumorigenesis. Overall, the results unravel the contribution of AI in
      colorectal cancer and provide a plausible explanation why so few genes are
      commonly affected by point mutations in cancers.

PMID- 30202009
TI  - Coordinated collective migration and asymmetric cell division in confluent human
      keratinocytes without wounding.
AB  - Epithelial sheet spreading is a fundamental cellular process that must be
      coordinated with cell division and differentiation to restore tissue integrity.
      Here we use consecutive serum deprivation and re-stimulation to reconstruct
      biphasic collective migration and proliferation in cultured sheets of human
      keratinocytes. In this system, a burst of long-range coordinated locomotion is
      rapidly generated throughout the cell sheet in the absence of wound edges.
      Migrating cohorts reach correlation lengths of several millimeters and display
      dependencies on epidermal growth factor receptor-mediated signaling, self
      propelled polarized migration, and a G1/G0 cell cycle environment. The migration
      phase is temporally and spatially aligned with polarized cell divisions
      characterized by pre-mitotic nuclear migration to the cell front and asymmetric
      partitioning of nuclear promyelocytic leukemia bodies and lysosomes to opposite
      daughter cells. This study investigates underlying mechanisms contributing to the
      stark contrast between cells in a static quiescent state compared to the long
      range coordinated collective migration seen in contact with blood serum.

PMID- 30202012
TI  - Identification of novel mouse and rat CB1R isoforms and in silico modeling of
      human CB1R for peripheral cannabinoid therapeutics.
AB  - Targeting peripheral CB1R is desirable for the treatment of metabolic syndromes
      without adverse neuropsychiatric effects. We previously reported a human hCB1b
      isoform that is selectively enriched in pancreatic beta-cells and hepatocytes,
      providing a potential peripheral therapeutic hCB1R target. It is unknown whether
      there are peripherally enriched mouse and rat CB1R (mCB1 and rCB1, respectively)
      isoforms. In this study, we found no evidence of peripherally enriched rodent CB1
      isoforms; however, some mCB1R isoforms are absent in peripheral tissues. We show
      that the mouse Cnr1 gene contains six exons that are transcribed from a single
      promoter. We found that mCB1A is a spliced variant of extended exon 1 and protein
      coding exon 6; mCB1B is a novel spliced variant containing unspliced exon 1,
      intron 1, and exon 2, which is then spliced to exon 6; and mCB1C is a spliced
      variant including all 6 exons. Using RNAscope in situ hybridization, we show that
      the isoforms mCB1A and mCB1B are expressed at a cellular level and colocalized in
      GABAergic neurons in the hippocampus and cortex. RT-qPCR reveals that mCB1A and
      mCB1B are enriched in the brain, while mCB1B is not expressed in the pancreas or
      the liver. Rat rCB1R isoforms are differentially expressed in primary cultured
      neurons, astrocytes, and microglia. We also investigated modulation of Cnr1
      expression by insulin in vivo and carried out in silico modeling of CB1R with
      JD5037, a peripherally restricted CB1R inverse agonist, using the published
      crystal structure of hCB1R. The results provide models for future CB1R peripheral
      targeting.

PMID- 30202013
TI  - Heterogeneity of cannabinoid ligand-induced modulations in intracellular Ca2+
      signals of mouse pancreatic acinar cells in vitro.
AB  - We recently reported that a CB2R agonist, GW405833 (GW), reduced both the ACh
      induced Ca2+ oscillations and the L-arginine-induced Ca2+ signal enhancement in
      mouse pancreatic acinar cells, suggesting that GW-induced inhibition may prevent
      the pathogenesis of acute pancreatitis. In this study, we aim to evaluate the
      effects of other cannabinoid ligands on Ca2+ signaling in acinar cells. Patch
      clamp whole-cell recordings were applied to measure ACh-induced intracellular
      Ca2+ oscillations in pancreatic acinar cells acutely dissociated from wild-type
      (WT), CB1R knockout (KO), and CB2R KO mice, and the pharmacological effects of
      various cannabinoid ligands on the Ca2+ oscillations were examined. We found that
      all the 8 CB2R agonists tested inhibited ACh-induced Ca2+ oscillations. Among
      them, GW, JWH133, and GP1a caused potent inhibition with IC50 values of 5.0, 6.7,
      and 1.2 MUmol/L, respectively. In CB2R KO mice or in the presence of a CB2R
      antagonist (AM630), the inhibitory effects of these 3 CB2R agonists were
      abolished, suggesting that they acted through the CB2Rs. The CB1R agonist ACEA
      also induced inhibition of Ca2+ oscillations that existed in CB1R KO mice and in
      the presence of a CB1R antagonist (AM251), suggesting a non-CB1R effect. In WT,
      CB1R KO, and CB2R KO mice, a nonselective CBR agonist, WIN55,212-2, inhibited
      Ca2+ oscillations, which was not mediated by CB1Rs or CB2Rs. The endogenous
      cannabinoid substance, 2-arachidonoylglycerol (2-AG), did not show an inhibitory
      effect on Ca2+ oscillations. In conclusion, CB2R agonists play critical roles in
      modulating Ca2+ signals in mouse pancreatic acinar cells, while other cannabinoid
      ligands modulate Ca2+ oscillations in a heterogeneous manner through a CB
      receptor or non-CB-receptor mechanism.

PMID- 30202011
TI  - Increased inflammation and brain glutamate define a subtype of depression with
      decreased regional homogeneity, impaired network integrity, and anhedonia.
AB  - Combined increases in peripheral inflammation and brain glutamate may identify a
      subtype of depression with distinct neuroimaging signatures. Two contrasting
      subgroups of depressed subjects-with and without combined elevations in plasma C
      reactive protein (CRP) and basal ganglia glutamate (high and low CRP-Glu,
      respectively) were identified by hierarchical clustering using plasma CRP
      (indexing peripheral inflammation) and magnetic resonance spectroscopy (MRS)
      based measurement of left basal ganglia glutamate. High CRP-Glu group status was
      associated with greater severity of anhedonia and cognitive and motor slowing.
      Local- and network-level measures of functional integrity were determined using
      brain oxygen level-dependent (BOLD)-oscillatory activity and graph theory.
      Greater decreases in concordance of oscillatory activity between neighboring
      voxels (Regional Homogeneity 'ReHo', p < 0.01) within the MRS volume-of-interest
      was associated with the High CRP-Glu subgroup. Using brain-wide, CRP-Glu ReHo
      contrast maps, a covariance network of 41 regions-of-interest (ROIs) with similar
      ReHo decreases was identified in the High CRP-Glu group and was located to brain
      structures previously implicated in depression. The 41-ROI network was further
      decomposed into four subnetworks. ReHo decreases within Subnetwork4-comprised of
      reward processing regions -was associated with anhedonia. Subnetwork4 ReHo also
      predicted decreased network integrity, which mediated the link between local ReHo
      and anhedonia in the Low but not High CRP-Glu group. These findings suggest that
      decreased ReHo and related disruptions in network integrity may reflect toxic
      effects of inflammation-induced increases in extrasynaptic glutamate signaling.
      Moreover, local BOLD oscillatory activity as reflected in ReHo might be a useful
      measure of target-engagement in the brain for treatment of inflammation-induced
      behaviors.

PMID- 30202014
TI  - Computational systems pharmacology analysis of cannabidiol: a combination of
      chemogenomics-knowledgebase network analysis and integrated in silico modeling
      and simulation.
AB  - With treatment benefits in both the central nervous system and the peripheral
      system, the medical use of cannabidiol (CBD) has gained increasing popularity.
      Given that the therapeutic mechanisms of CBD are still vague, the systematic
      identification of its potential targets, signaling pathways, and their
      associations with corresponding diseases is of great interest for researchers. In
      the present work, chemogenomics-knowledgebase systems pharmacology analysis was
      applied for systematic network studies to generate CBD-target, target-pathway,
      and target-disease networks by combining both the results from the in silico
      analysis and the reported experimental validations. Based on the network
      analysis, three human neuro-related rhodopsin-like GPCRs, i.e., 5
      hydroxytryptamine receptor 1 A (5HT1A), delta-type opioid receptor (OPRD) and G
      protein-coupled receptor 55 (GPR55), were selected for close evaluation.
      Integrated computational methodologies, including homology modeling, molecular
      docking, and molecular dynamics simulation, were used to evaluate the protein-CBD
      binding modes. A CBD-preferred pocket consisting of a hydrophobic cavity and
      backbone hinges was proposed and tested for CBD-class A GPCR binding. Finally,
      the neurophysiological effects of CBD were illustrated at the molecular level,
      and dopamine receptor 3 (DRD3) was further predicted to be an active target for
      CBD.

PMID- 30202015
TI  - Autophagy proteins suppress protective type I interferon signalling in response
      to the murine gut microbiota.
AB  - As a conserved pathway that lies at the intersection between host defence and
      cellular homeostasis, autophagy serves as a rheostat for immune reactions. In
      particular, autophagy suppresses excess type I interferon (IFN-I) production in
      response to viral nucleic acids. It is unknown how this function of autophagy
      relates to the intestinal barrier where host-microbe interactions are pervasive
      and perpetual. Here, we demonstrate that mice deficient in autophagy proteins are
      protected from the intestinal bacterial pathogen Citrobacter rodentium in a
      manner dependent on IFN-I signalling and nucleic acid sensing pathways. Enhanced
      IFN-stimulated gene expression in intestinal tissue of autophagy-deficient mice
      in the absence of infection was mediated by the gut microbiota. Additionally,
      monocytes infiltrating into the autophagy-deficient intestinal microenvironment
      displayed an enhanced inflammatory profile and were necessary for protection
      against C. rodentium. Finally, we demonstrate that the microbiota-dependent IFN-I
      production that occurs in the autophagy-deficient host also protects against
      chemical injury of the intestine. Thus, autophagy proteins prevent a spontaneous
      IFN-I response to microbiota that is beneficial in the presence of infectious and
      non-infectious intestinal hazards. These results identify a role for autophagy
      proteins in controlling the magnitude of IFN-I signalling at the intestinal
      barrier.

PMID- 30202016
TI  - Host resistance to pulmonary Mycobacterium tuberculosis infection requires CD153
      expression.
AB  - Mycobacterium tuberculosis infection (Mtb) is the leading cause of death due to a
      single infectious agent and is among the top ten causes of all human deaths
      worldwide1. CD4 T cells are essential for resistance to Mtb infection, and for
      decades it has been thought that IFNgamma production is the primary mechanism of
      CD4 T-cell-mediated protection2,3. However, IFNgamma responses do not correlate
      with host protection, and several reports demonstrate that additional anti
      tuberculosis CD4 T-cell effector functions remain unaccounted for4-8. Here we
      show that the tumour-necrosis factor (TNF) superfamily molecule CD153 (encoded by
      the gene Tnfsf8) is required for control of pulmonary Mtb infection by CD4 T
      cells. In Mtb-infected mice, CD153 expression is highest on Mtb-specific T helper
      1 (TH1) cells in the lung tissue parenchyma, but its induction does not require
      TH1 cell polarization. CD153-deficient mice develop high pulmonary bacterial
      loads and succumb early to Mtb infection. Reconstitution of T-cell-deficient
      hosts with either Tnfsf8-/- or Ifng-/- CD4 T cells alone fails to rescue mice
      from early mortality, but reconstitution with a mixture of Tnfsf8-/- and Ifng-/-
      CD4 T cells provides similar protection as wild-type T cells. In Mtb-infected non
      human primates, CD153 expression is much higher on Ag-specific CD4 T cells in the
      airways compared to blood, and the frequency of Mtb-specific CD153-expressing CD4
      T cells inversely correlates with bacterial loads in granulomas. In Mtb-infected
      humans, CD153 defines a subset of highly polyfunctional Mtb-specific CD4 T cells
      that are much more abundant in individuals with controlled latent Mtb infection
      compared to those with active tuberculosis. In all three species, Mtb-specific
      CD8 T cells did not upregulate CD153 following peptide stimulation. Thus, CD153
      is a major immune mediator of host protection against pulmonary Mtb infection and
      CD4 T cells are one important source of this molecule.

PMID- 30202017
TI  - Male offspring born to mildly ZIKV-infected mice are at risk of developing
      neurocognitive disorders in adulthood.
AB  - Congenital Zika virus (ZIKV) syndrome may cause fetal microcephaly in ~1% of
      affected newborns. Here, we investigate whether the majority of clinically
      inapparent newborns might suffer from long-term health impairments not readily
      visible at birth. Infection of immunocompetent pregnant mice with high-dose ZIKV
      caused severe offspring phenotypes, such as fetal death, as expected. By
      contrast, low-dose (LD) maternal ZIKV infection resulted in reduced fetal birth
      weight but no other obvious phenotypes. Male offspring born to LD ZIKV-infected
      mothers had increased testosterone (TST) levels and were less likely to survive
      in utero infection compared to their female littermates. Males also presented an
      increased number of immature neurons in apical and basal hippocampal dendrites,
      while female offspring had immature neurons in basal dendrites only. Moreover,
      male offspring with high but not very high (storm) TST levels were more likely to
      suffer from learning and memory impairments compared to females. Future studies
      are required to understand the impact of TST on neuropathological and
      neurocognitive impairments in later life. In summary, increased sex-specific
      vigilance is required in countries with high ZIKV prevalence, where impaired
      neurodevelopment may be camouflaged by a healthy appearance at birth.

PMID- 30202018
TI  - Electronic and Hydrogen Storage Properties of Li-Terminated Linear Boron Chains
      Studied by TAO-DFT.
AB  - It has been extremely difficult for conventional computational approaches to
      reliably predict the properties of multi-reference systems (i.e., systems
      possessing radical character) at the nanoscale. To resolve this, we employ
      thermally-assisted-occupation density functional theory (TAO-DFT) to predict the
      electronic and hydrogen storage properties of Li-terminated linear boron chains
      (Li2Bn), with n boron atoms (n = 6, 8, ..., and 16). From our TAO-DFT results,
      Li2Bn, which possess radical character, can bind up to 4 H2 molecules per Li,
      with the binding energies in the desirable regime (between 20 and 40 kJ/mol per
      H2). The hydrogen gravimetric storage capacities of Li2Bn range from 7.9 to 17.0
      wt%, achieving the ultimate goal of the United States Department of Energy.
      Accordingly, Li2Bn could be promising media for storing and releasing H2 at
      temperatures much higher than the boiling point of liquid nitrogen.

PMID- 30202021
TI  - Hybrid System of an Optical Nanofibre and a Single Quantum Dot Operated at
      Cryogenic Temperatures.
AB  - Recent progress in quantum nanophotonics brings novel ways for manipulating
      single photons in various nano-waveguides. Among them, one promising approach is
      to use optical nanofibres (ONFs), tapered optical fibres with sub-wavelength
      diameter waists. Here, we develop a hybrid system of an ONF and a single quantum
      dot (QD) operated at cryogenic temperatures. We deposit a single colloidal CdSe
      QD on an ONF waist and observe emitted photons through the fibre guided modes. We
      systematically investigate emission characteristics for both the neutral exciton
      and charged exciton (trion) for one specific QD. We quantitatively show that the
      trion at cryogenic temperatures acts as an excellent quantum emitter for the ONF
      and QD hybrid system. The present ONF/QD hybrid system at cryogenic temperatures
      paves the way for quantum information technologies for manipulating single
      photons in fibre networks.

PMID- 30202019
TI  - The genomic landscape of cutaneous SCC reveals drivers and a novel azathioprine
      associated mutational signature.
AB  - Cutaneous squamous cell carcinoma (cSCC) has a high tumour mutational burden (50
      mutations per megabase DNA pair). Here, we combine whole-exome analyses from 40
      primary cSCC tumours, comprising 20 well-differentiated and 20 moderately/poorly
      differentiated tumours, with accompanying clinical data from a longitudinal study
      of immunosuppressed and immunocompetent patients and integrate this analysis with
      independent gene expression studies. We identify commonly mutated genes, copy
      number changes and altered pathways and processes. Comparisons with tumour
      differentiation status suggest events which may drive disease progression.
      Mutational signature analysis reveals the presence of a novel signature
      (signature 32), whose incidence correlates with chronic exposure to the
      immunosuppressive drug azathioprine. Characterisation of a panel of 15 cSCC
      tumour-derived cell lines reveals that they accurately reflect the mutational
      signatures and genomic alterations of primary tumours and provide a valuable
      resource for the validation of tumour drivers and therapeutic targets.

PMID- 30202020
TI  - Routine use of HbA1c amongst inpatients hospitalised with decompensated heart
      failure and the association of dysglycaemia with outcomes.
AB  - Diabetes is an independent risk factor for development of heart failure and has
      been associated with poor outcomes in these patients. The prevalence of diabetes
      continues to rise. Using routine HbA1c measurements on inpatients at a tertiary
      hospital, we aimed to investigate the prevalence of diabetes amongst patients
      hospitalised with decompensated heart failure and the association of dysglycaemia
      with hospital outcomes and mortality. 1191 heart failure admissions were
      identified and of these, 49% had diabetes (HbA1c >= 6.5%) and 34% had pre
      diabetes (HbA1c 5.7-6.4%). Using a multivariable analysis adjusting for age,
      Charlson comorbidity score (excluding diabetes and age) and estimated glomerular
      filtration rate, diabetes was not associated with length of stay (LOS), Intensive
      Care Unit (ICU) admission or 28-day readmission. However, diabetes was associated
      with a lower risk of 6-month mortality. This finding was also supported using
      HbA1c as a continuous variable. The diabetes group were more likely to have
      diastolic dysfunction and to be on evidence-based cardiac medications. These
      observational data are hypothesis generating and possible explanations include
      that more diabetic patients were on medications that have proven mortality
      benefit or prevent cardiac remodelling, such as renin-angiotensin system
      antagonists, which may modulate the severity of heart failure and its
      consequences.

PMID- 30202022
TI  - Characterisation of pathogen-specific regions and novel effector candidates in
      Fusarium oxysporum f. sp. cepae.
AB  - A reference-quality assembly of Fusarium oxysporum f. sp. cepae (Foc), the
      causative agent of onion basal rot has been generated along with genomes of
      additional pathogenic and non-pathogenic isolates of onion. Phylogenetic analysis
      confirmed a single origin of the Foc pathogenic lineage. Genome alignments with
      other F. oxysporum ff. spp. and non pathogens revealed high levels of syntenic
      conservation of core chromosomes but little synteny between lineage specific (LS)
      chromosomes. Four LS contigs in Foc totaling 3.9 Mb were designated as pathogen
      specific (PS). A two-fold increase in segmental duplication events was observed
      between LS regions of the genome compared to within core regions or from LS
      regions to the core. RNA-seq expression studies identified candidate effectors
      expressed in planta, consisting of both known effector homologs and novel
      candidates. FTF1 and a subset of other transcription factors implicated in
      regulation of effector expression were found to be expressed in planta.

PMID- 30202023
TI  - Real-world retrospective cohort study ARCTIC shows burden of comorbidities in
      Swedish COPD versus non-COPD patients.
AB  - This study aimed to generate real-world evidence to assess the burden of
      comorbidities in COPD patients, to effectively manage these patients and optimize
      the associated healthcare resource allocation. ARCTIC is a large, real-world,
      retrospective cohort study conducted in Swedish COPD patients using electronic
      medical record data collected between 2000 and 2014. These patients were studied
      for prevalence of various comorbidities and for association of these
      comorbidities with exacerbations, mortality, and healthcare costs compared with
      an age-, sex-, and comorbidities-matched non-COPD reference population. A total
      of 17,479 patients with COPD were compared with 84,514 non-COPD reference
      population. A significantly higher prevalence of various comorbidities was
      observed in COPD patients 2 years post-diagnosis vs. reference population, with
      the highest percentage increase observed for cardiovascular diseases (81.8% vs.
      30.7%). Among the selected comorbidities, lung cancer was relatively more
      prevalent in COPD patients vs. reference population (relative risk, RR = 5.97, p
      < 0.0001). Ischemic heart disease, hypertension, depression, anxiety, sleep
      disorders, osteoporosis, osteoarthritis, and asthma caused increased mortality
      rates in COPD patients. Comorbidities that were observed to be significantly
      associated with increased number of severe exacerbations in COPD patients
      included heart failure, ischemic heart disease, depression/anxiety, sleep
      disorders, osteoporosis, lung cancer, and stroke. The cumulative healthcare costs
      associated with comorbidities over 2 years after the index date were observed to
      be significantly higher in COPD patients (?27,692) vs. reference population
      (?5141) (p < 0.0001). The data support the need for patient-centered treatment
      strategies and targeted healthcare resource allocation to reduce the humanistic
      and economic burden associated with COPD comorbidities.

PMID- 30202024
TI  - Interaction of TBC1D9B with Mammalian ATG8 Homologues Regulates Autophagic Flux.
AB  - Autophagosomes are double-membraned vesicles with cytosolic components. Their
      destination is to fuse with the lysosome to degrade the enclosed cargo. However,
      autophagosomes may be fused with other membrane compartments and possibly
      misguided by the RAB molecules from these compartments. The mechanisms ensuring
      the proper trafficking are not well understood. Yeast ATG8 and its mammalian
      homologues are critically involved in the autophagosome formation and expansion.
      We hypothesized that they could be also involved in the regulation of
      autophagosome trafficking. Using the yeast two-hybrid system, we found that
      TBC1D9B, a GTPase activating protein for RAB11A, interacted with LC3B. TBC1D9B
      could also interact with other mammalian ATG8 homologues. This interaction was
      confirmed with purified proteins in vitro, and by co-immunoprecipitation in vivo.
      The interacting domain of TBC1D9B with LC3 was further determined, which is
      unique and different from the known LC3-interacting region previously defined in
      other LC3-interacting molecules. Functionally, TBC1D9B could be co-localized with
      LC3B on the autophagosome membranes. Inhibition of TBC1D9B suppressed the
      turnover of membrane-bound LC3B and the autophagic degradation of long-lived
      proteins. TBC1D9B can thus positively regulate autophagic flux, possibly through
      its GTPase activity to inactivate RAB11A, facilitating the proper destination of
      the autophagosomes to the degradation.

PMID- 30202025
TI  - Rotations of macromolecules affect nonspecific biological responses to magnetic
      fields.
AB  - We have previously proposed that there are at least two initial molecular
      transduction mechanisms needed to explain specific and nonspecific biological
      effects of weak magnetic fields. For the specific effect associated with animal
      magnetic navigation, the radical pair mechanism is the leading hypothesis; it
      associates the specialised magnetic sense with the radical pairs located in the
      eye retina. In contrast to the magnetic sense, nonspecific effects occur through
      the interaction of magnetic fields with magnetic moments dispersed over the
      organism. However, it is unlikely that the radical pair mechanism can explain
      such nonspecific phenomena. In order to explain these, we further develop our
      physical model for the case of magnetic moments residing in rotating molecules.
      It is shown that, in some conditions, the precession of the magnetic moments that
      reside on rotating molecules can be slowed relative to the immediate biophysical
      structures. In terms of quantum mechanics this corresponds to the mixing of the
      quantum levels of magnetic moments. Hence this mechanism is called the Level
      Mixing Mechanism, or the LMM. The results obtained are magnetic field-dependences
      that are in good agreement with known experiments where biological effects arise
      in response to the reversal of the magnetic field vector.

PMID- 30202027
TI  - Ballistic and Collisional Flow Contributions to Anti-Fourier Heat Transfer in
      Rarefied Cavity Flow.
AB  - This paper investigates anti-Fourier heat transfer phenomenon in a rarefied gas
      confined within a lid-driven cavity using a novel flow decomposition technique in
      the direct simulation Monte Carlo (DSMC) method proposed by Stefanov and co
      workers. An isothermal cavity with different degrees of flow rarefaction from
      near continuum to mid transition regimes was considered to investigate cold-to
      hot heat transfer from ballistic/collision flow decomposition viewpoint. A new
      cold-to-hot heat transfer indicator in the form of a scalar product of normalized
      heat flow vector and normalized temperature gradient vector has been introduced
      for the overall, ballistic and collision parts of these vectors. Using the new
      indicator, contributions of ballistic and collision flow parts to temperature and
      heat flux components was investigated with a specific emphasis on the cold-to-hot
      heat transfer phenomenon. We demonstrated that both ballistic and collision flow
      parts contribute to the occurrence of cold-to-hot heat transfer. However, it was
      found out that considered separately both ballistic and collision parts of heat
      transfer, when related to corresponding ballistic and collision temperature
      fields, they are ever hot-to-cold for all degrees of flow rarefaction. Thus, cold
      to-hot heat transfer is a result of a subtle interplay between ballistic and
      collision parts in the slip and transition Knudsen regimes.

PMID- 30202026
TI  - In vivo functional characterisation of pheromone binding protein-1 in the
      silkmoth, Bombyx mori.
AB  - Male moths detect sex pheromones emitted by conspecific females with high
      sensitivity and specificity by the olfactory sensilla on their antennae.
      Pheromone binding proteins (PBPs) are highly enriched in the sensillum lymph of
      pheromone sensitive olfactory sensilla and are supposed to contribute to the
      sensitivity and selectivity of pheromone detection in moths. However, the
      functional role of PBPs in moth sex pheromone detection in vivo remains obscure.
      In the silkmoth, Bombyx mori, female moths emit bombykol as a single attractive
      sex pheromone component along with a small amount of bombykal that negatively
      modulates the behavioural responses to bombykol. A pair of olfactory receptor
      neurons, specifically tuned to bombykol or bombykal, co-localise in the
      trichodeum sensilla, the sensillum lymph of which contains a single PBP, namely,
      BmPBP1. We analysed the roles of BmPBP1 using BmPBP1-knockout silkmoth lines
      generated by transcription activator-like effector nuclease-mediated gene
      targeting. Electroantennogram analysis revealed that the peak response amplitudes
      of BmPBP1-knockout male antennae to bombykol and bombykal were significantly
      reduced by a similar percentage when compared with those of the wild-type males.
      Our results indicate that BmPBP1 plays a crucial role in enhancing the
      sensitivity, but not the selectivity, of sex pheromone detection in silkmoths.

PMID- 30202028
TI  - Comparative study of the toxicity between three non-steroidal anti-inflammatory
      drugs and their UV/Na2S2O8 degradation products on Cyprinus carpio.
AB  - The efficiency of advanced oxidation processes (AOPs) for disposing of non
      steroidal anti-inflammatory drugs (NSAIDs) has been widely studied, but the
      environmental fates and effects of the NSAIDs and their degradation products
      (DPs) are poorly understood. In this study, the efficiency of ultraviolet
      light/Na2S2O8 (UV/PS) in degrading three NSAIDs-diclofenac, naproxen, and
      ibuprofen-and the toxicity of their DPs on Cyprinus carpio (C. carpio) was
      investigated. Results showed that the three NSAIDs can be completely removed
      (removal rate > 99.9%) by UV/PS, while the mineralization rate of the NSAIDs was
      only 28%. When C. carpio were exposed to 0.1 MUM NSAIDs, 10 MUM persulfate (PS),
      and 0.1 MUM DPs of the NSAIDs for 96 h, respectively, the toxicity effects are as
      the NSAID DPs > PS > NSAIDs. Research results into the time-dependent effect of
      NSAID DPs on C. carpio demonstrated that obvious toxicity effects were observed
      in the first 48 hours, and the toxicity effects strengthened over time. NSAID DPs
      may have more severe toxicity effects than NSAIDs on C. carpio; therefore, the
      operating conditions of UV/PS must be optimized to eliminate the ecotoxicity of
      DPs.

PMID- 30202029
TI  - Distinct mental trainings differentially affect altruistically motivated, norm
      motivated, and self-reported prosocial behaviour.
AB  - Global challenges such as climate change or the refugee crises emphasize the
      necessity of altruism and cooperation. In a large-scale 9-month intervention
      study, we investigated the malleability of prosociality by three distinct mental
      trainings cultivating attention, socio-affective, or socio-cognitive skills. We
      assessed numerous established measures of prosociality that capture three core
      facets: Altruistically motivated behaviours, norm motivated behaviours, and self
      reported prosociality. Results of multiple time point confirmatory factor
      analyses support the validity and temporal stability of this model. Furthermore,
      linear mixed effects models reveal differential effects of mental trainings on
      the subcomponents of prosociality: Only training care and compassion effectively
      boosted altruistically motivated behaviour. No effects were revealed for norm
      based behaviour. Self-reported prosociality increased with all training modules;
      this increase was, however, unrelated to changes in task-based measures of
      altruistic behaviour. These findings corroborate our motivation-based framework
      of prosociality, challenge economic views of fixed preferences by showing that
      socio-affective training boosts altruism, and inform policy makers and society
      about how to increase global cooperation.

PMID- 30202030
TI  - Adjunctive use of celecoxib with anti-tuberculosis drugs: evaluation in a whole
      blood bactericidal activity model.
AB  - COX-2 inhibition may be of benefit in the treatment of tuberculosis (TB) through
      a number of pathways including efflux pump inhibition (increasing intracellular
      TB drug levels) and diverse effects on inflammation and the immune response. We
      investigated celecoxib (a COX-2 inhibitor) alone and with standard anti
      tuberculosis drugs in the whole-blood bactericidal activity (WBA) model. Healthy
      volunteers took a single dose of celecoxib (400 mg), followed (after 1 week) by a
      single dose of either rifampicin (10 mg/kg) or pyrazinamide (25 mg/kg), followed
      (after 2 or 7 days respectively) by the same anti-tuberculosis drug with
      celecoxib. WBA was measured at intervals until 8 hours post-dose (by inoculating
      blood samples with Mycobacterium tuberculosis and estimating the change in
      bacterial colony forming units after 72 hours incubation). Celecoxib had no
      activity alone in the WBA assay (cumulative WBA over 8 hours post-dose: 0.03 +/-
      0.01DeltalogCFU, p = 1.00 versus zero). Celecoxib did not increase cumulative WBA
      of standard TB drugs (mean cumulative WBA -0.10 +/- 0.13DeltalogCFU versus -0.10
      +/- 0.12DeltalogCFU for TB drugs alone versus TB drugs and celecoxib; mean
      difference -0.01, 95% CI -0.02 to 0.00; p = 0.16). The lack of benefit of
      celecoxib suggests that efflux pump inhibition or eicosanoid pathway-related
      responses are of limited importance in mycobacterial killing in the WBA assay.

PMID- 30202032
TI  - Auxin sensing is a property of an unstructured domain in the Auxin Response
      Factor ETTIN of Arabidopsis thaliana.
AB  - The plant hormone auxin regulates numerous aspects of the plant life cycle. Auxin
      signalling is mediated by auxin response factors (ARFs) that dimerise with
      modulating Aux/IAA repressors. ARF3 (ETTIN or ETT) is atypical as it does not
      interact with Aux/IAA repressors. It is proposed to be a non-canonical auxin
      sensor, regulating diverse functions essential for development. This sensing
      ability relies on a unique C-terminal ETT specific domain (ES domain). Alignments
      of ETT orthologues across the angiosperm phylum revealed that the length and
      sequence identities of ES domains are poorly conserved. Computational predictors
      suggested the ES domains to be intrinsically disordered, explaining their
      tolerance of insertions, deletions and mutations during evolution. Nevertheless,
      five highly conserved short linear motifs were identified suggesting functional
      significance. High-throughput library screening identified an almost full-length
      soluble ES domain that did not bind auxin directly, but exhibited a dose
      dependent response in a yeast two-hybrid system against the Arabidopsis
      INDEHISCENT (IND) transcription factor. Circular dichroism confirmed the domain
      was disordered. The identification and purification of this domain opens the way
      to the future characterisation of the ETT auxin-sensing mechanism in planta and
      an improved understanding of auxin-mediated regulation.

PMID- 30202031
TI  - ABC transporter mis-splicing associated with resistance to Bt toxin Cry2Ab in
      laboratory- and field-selected pink bollworm.
AB  - Evolution of pest resistance threatens the benefits of genetically engineered
      crops that produce Bacillus thuringiensis (Bt) insecticidal proteins. Strategies
      intended to delay pest resistance are most effective when implemented
      proactively. Accordingly, researchers have selected for and analyzed resistance
      to Bt toxins in many laboratory strains of pests before resistance evolves in the
      field, but the utility of this approach depends on the largely untested
      assumption that laboratory- and field-selected resistance to Bt toxins are
      similar. Here we compared the genetic basis of resistance to Bt toxin Cry2Ab,
      which is widely deployed in transgenic crops, between laboratory- and field
      selected populations of the pink bollworm (Pectinophora gossypiella), a global
      pest of cotton. We discovered that resistance to Cry2Ab is associated with
      mutations disrupting the same ATP-binding cassette transporter gene (PgABCA2) in
      a laboratory-selected strain from Arizona, USA, and in field-selected populations
      from India. The most common mutation, loss of exon 6 caused by alternative
      splicing, occurred in resistant larvae from both locations. Together with
      previous data, the results imply that mutations in the same gene confer Bt
      resistance in laboratory- and field-selected strains and suggest that focusing on
      ABCA2 genes may help to accelerate progress in monitoring and managing resistance
      to Cry2Ab.

PMID- 30202033
TI  - Viral infections in fire ants lead to reduced foraging activity and dietary
      changes.
AB  - Despite the presence of conserved innate immune function, many insects have
      evolved a variety of mechanical, chemical, and behavioral defensive responses to
      pathogens. Illness-induced anorexia and dietary changes are two behavioral
      defensive strategies found in some solitary insects, but little is known
      regarding the role of such behaviors in social insects, especially in ants. In
      the present study we examined if such reduced foraging activity exists for a
      social insect, the invasive fire ant Solenopsis invicta, and its viral pathogen,
      Solenopsis invicta virus 1 (SINV-1). Virus-free fire ant colonies were split into
      two colony fragments, one of which subsequently was inoculated with SINV-1. Four
      food resources with different macronutrient ratios were presented to both colony
      fragments. SINV-1-inoculated colony fragments consistently displayed reduced
      foraging performance (e.g., foraging intensity and recruitment efficiency), a
      decline in lipid intake, and a shift in dietary preference to carbohydrate-rich
      foods compared with virus-free fragments. These findings provide the first
      evidence for virus-induced behavioral responses and dietary shifts in shaping the
      host-pathogen interactions in fire ants. The findings also suggest a possible
      mechanism for how fire ant colonies respond to viral epidemics. Potential
      implications of these behavioral differences for current management strategies
      are discussed.

PMID- 30202035
TI  - Modified Bethesda system informing cytopathologic adequacy improves malignancy
      risk stratification in nodules considered benign or atypia(follicular lesion) of
      undetermined significance.
AB  - We modified the nondiagnostic/unsatisfactory category of the Bethesda system for
      reporting thyroid cytopathology to inform cytopathologic adequacy to better
      stratify the malignancy risk. Malignancy rates from 1,450 cytopathologic
      specimens not satisfying adequacy criteria from April 2011 to March 2016 were
      calculated based on sub-classification of the nondiagnostic/unsatisfactory
      category and sonographic patterns using matched surgical pathology. Rates were
      compared with those of 1,446 corresponding adequate specimens from July to
      December 2013. Upon resection, 63.2% of nondiagnostic, 36.7% of unsatisfactory +
      benign, 72.5% of unsatisfactory + atypia (follicular lesion) of undetermined
      significance, 98.1% of unsatisfactory + suspicious for malignancy, and 100.0% of
      unsatisfactory + malignant cases were confirmed to be malignant on surgical
      pathology. In nodules with inadequate specimens, those with high suspicion
      sonographic patterns had a malignancy rate (93.2%) higher than the others (45.5%)
      (p < 0.001). Nodules with unsatisfactory + benign specimens had a higher
      malignancy rate (36.7%) than satisfactory benign specimens (14.3%) (p = 0.020).
      For atypia (follicular lesion) of undetermined significance, the malignancy rate
      of inadequate specimens (72.5%) was higher than that of adequate specimens
      (51.3%) (p = 0.027). Sparse cellular samples with a few groups of benign
      follicular cells should not represent a benign lesion. There might be value in
      qualifying atypia (follicular lesion) of undetermined significance cases less
      than optimal.

PMID- 30202037
TI  - Comment: Hyperbaric oxygen can induce angiogenesis and recover erectile function.

PMID- 30202036
TI  - Ultra-diluted Toxicodendron pubescens attenuates pro-inflammatory cytokines and
      ROS- mediated neuropathic pain in rats.
AB  - Despite the availability of multiple therapeutic agents, the search for novel
      pain management of neuropathic pain is still a challenge. Oxidative stress and
      inflammatory signaling are prominently involved in clinical manifestation of
      neuropathic pain. Toxicodendron pubescens, popularly known as Rhus Tox (RT) is
      recommended in alternative medicines as an anti-inflammatory and analgesic
      remedy. Earlier, we reported anti-inflammatory, anti-arthritic and
      immunomodulatory activities of Rhus Tox. In continuation, we evaluated
      antinociceptive efficacy of Rhus Tox in the neuropathic pain and delineated its
      underlying mechanism. Initially, in-vitro assay using LPS-mediated ROS-induced U
      87 glioblastoma cells was performed to study the effect of Rhus Tox on reactive
      oxygen species (ROS), anti-oxidant status and cytokine profile. Rhus Tox
      decreased oxidative stress and cytokine release with restoration of anti-oxidant
      systems. Chronic treatment with Rhus Tox ultra dilutions for 14 days ameliorated
      neuropathic pain revealed as inhibition of cold, warm and mechanical allodynia
      along with improved motor nerve conduction velocity (MNCV) in constricted nerve.
      Rhus Tox decreased the oxidative and nitrosative stress by reducing
      malondialdehyde (MDA) and nitric oxide (NO) content, respectively along with up
      regulated glutathione (GSH), superoxide dismutase (SOD) and catalase activity in
      sciatic nerve of rats. Notably, Rhus Tox treatment caused significant reductions
      in the levels of tumor necrosis factor (TNF-alpha), interleukin-6 (IL-6) and
      interleukin-1beta (IL-1beta) as compared with CCI-control group. Protective
      effect of Rhus Tox against CCI-induced sciatic nerve injury in histopathology
      study was exhibited through maintenance of normal nerve architecture and
      inhibition of inflammatory changes. Overall, neuroprotective effect of Rhus Tox
      in CCI-induced neuropathic pain suggests the involvement of anti-oxidative and
      anti-inflammatory mechanisms.

PMID- 30202034
TI  - An integrated genomic analysis of anaplastic meningioma identifies prognostic
      molecular signatures.
AB  - Anaplastic meningioma is a rare and aggressive brain tumor characterised by
      intractable recurrences and dismal outcomes. Here, we present an integrated
      analysis of the whole genome, transcriptome and methylation profiles of primary
      and recurrent anaplastic meningioma. A key finding was the delineation of
      distinct molecular subgroups that were associated with diametrically opposed
      survival outcomes. Relative to lower grade meningiomas, anaplastic tumors
      harbored frequent driver mutations in SWI/SNF complex genes, which were confined
      to the poor prognosis subgroup. Aggressive disease was further characterised by
      transcriptional evidence of increased PRC2 activity, stemness and epithelial-to
      mesenchymal transition. Our analyses discern biologically distinct variants of
      anaplastic meningioma with prognostic and therapeutic significance.

PMID- 30202038
TI  - PoreDesigner for tuning solute selectivity in a robust and highly permeable outer
      membrane pore.
AB  - Monodispersed angstrom-size pores embedded in a suitable matrix are promising for
      highly selective membrane-based separations. They can provide substantial energy
      savings in water treatment and small molecule bioseparations. Such pores present
      as membrane proteins (chiefly aquaporin-based) are commonplace in biological
      membranes but difficult to implement in synthetic industrial membranes and have
      modest selectivity without tunable selectivity. Here we present PoreDesigner, a
      design workflow to redesign the robust beta-barrel Outer Membrane Protein F as a
      scaffold to access three specific pore designs that exclude solutes larger than
      sucrose (>360 Da), glucose (>180 Da), and salt (>58 Da) respectively.
      PoreDesigner also enables us to design any specified pore size (spanning 3-10 A),
      engineer its pore profile, and chemistry. These redesigned pores may be ideal for
      conducting sub-nm aqueous separations with permeabilities exceeding those of
      classical biological water channels, aquaporins, by more than an order of
      magnitude at over 10 billion water molecules per channel per second.

PMID- 30202039
TI  - A comparative analysis of approaches to network-dismantling.
AB  - Estimating, understanding, and improving the robustness of networks has many
      application areas such as bioinformatics, transportation, or computational
      linguistics. Accordingly, with the rise of network science for modeling complex
      systems, many methods for robustness estimation and network dismantling have been
      developed and applied to real-world problems. The state-of-the-art in this field
      is quite fuzzy, as results are published in various domain-specific venues and
      using different datasets. In this study, we report, to the best of our knowledge,
      on the analysis of the largest benchmark regarding network dismantling. We
      reimplemented and compared 13 competitors on 12 types of random networks,
      including ER, BA, and WS, with different network generation parameters. We find
      that network metrics, proposed more than 20 years ago, are often non-dominating
      competitors, while many recently proposed techniques perform well only on
      specific network types. Besides the solution quality, we also investigate the
      execution time. Moreover, we analyze the similarity of competitors, as induced by
      their node rankings. We compare and validate our results on real-world networks.
      Our study is aimed to be a reference for selecting a network dismantling method
      for a given network, considering accuracy requirements and run time constraints.

PMID- 30202040
TI  - Radiomics of US texture features in differential diagnosis between triple
      negative breast cancer and fibroadenoma.
AB  - Triple-negative breast cancer (TNBC) is sometimes mistaken for fibroadenoma due
      to its tendency to show benign morphology on breast ultrasound (US) albeit its
      aggressive nature. This study aims to develop a radiomics score based on US
      texture analysis for differential diagnosis between TNBC and fibroadenoma, and to
      evaluate its diagnostic performance compared with pathologic results. We
      retrospectively included 715 pathology-proven fibroadenomas and 186 pathology
      proven TNBCs which were examined by three different US machines. We developed the
      radiomics score by using penalized logistic regression with a least absolute
      shrinkage and selection operator (LASSO) analysis from 730 extracted features
      consisting of 14 intensity-based features, 132 textural features and 584 wavelet
      based features. The constructed radiomics score showed significant difference
      between fibroadenoma and TNBC for all three US machines (p < 0.001). Although the
      radiomics score showed dependency on the type of US machine, we developed more
      elaborate radiomics score for a subgroup in which US examinations were performed
      with iU22. This subsequent radiomics score also showed good diagnostic
      performance, even for BI-RADS category 3 or 4a lesions (AUC 0.782) which were
      presumed as probably benign or low suspicious of malignancy by radiologists. It
      was expected to assist radiologist's diagnosis and reduce the number of invasive
      biopsies, although US standardization should be overcome before clinical
      application.

PMID- 30202041
TI  - Exploring predictive biomarkers from clinical genome-wide association studies via
      multidimensional hierarchical mixture models.
AB  - Although the detection of predictive biomarkers is of particular importance for
      the development of accurate molecular diagnostics, conventional statistical
      analyses based on gene-by-treatment interaction tests lack sufficient statistical
      power for this purpose, especially in large-scale clinical genome-wide studies
      that require an adjustment for multiplicity of a huge number of tests. Here we
      demonstrate an alternative efficient multi-subgroup screening method using
      multidimensional hierarchical mixture models developed to overcome this issue,
      with application to stroke and breast cancer randomized clinical trials with
      genomic data. We show that estimated effect size distributions of single
      nucleotide polymorphisms (SNPs) associated with outcomes, which could provide
      clues for exploring predictive biomarkers, optimizing individualized treatments,
      and understanding biological mechanisms of diseases. Furthermore, using this
      method we detected three new SNPs that are associated with blood homocysteine
      levels, which are strongly associated with the risk of stroke. We also detected
      six new SNPs that are associated with progression-free survival in breast cancer
      patients.

PMID- 30202042
TI  - Microfabricated tuneable and transferable porous PDMS membranes for Organs-on
      Chips.
AB  - We present a novel and highly reproducible process to fabricate transferable
      porous PDMS membranes for PDMS-based Organs-on-Chips (OOCs) using
      microelectromechanical systems (MEMS) fabrication technologies. Porous PDMS
      membranes with pore sizes down to 2.0 MUm in diameter and a wide porosity range
      (2-65%) can be fabricated. To overcome issues normally faced when using replica
      moulding and extend the applicability to most OOCs and improve their scalability
      and reproducibility, the process includes a sacrificial layer to easily transfer
      the membranes from a silicon carrier to any PDMS-based OOC. The highly reliable
      fabrication and transfer method does not need of manual handling to define the
      pore features (size, distribution), allowing very thin (<10 MUm) functional
      membranes to be transferred at chip level with a high success rate (85%). The
      viability of cell culturing on the porous membranes was assessed by culturing two
      different cell types on transferred membranes in two different OOCs. Human
      umbilical endothelial cells (HUVEC) and MDA-MB-231 (MDA) cells were successfully
      cultured confirming the viability of cell culturing and the biocompatibility of
      the membranes. The results demonstrate the potential of controlling the porous
      membrane features to study cell mechanisms such as transmigrations, monolayer
      formation, and barrier function. The high control over the membrane
      characteristics might consequently allow to intentionally trigger or prevent
      certain cellular responses or mechanisms when studying human physiology and
      pathology using OOCs.

PMID- 30202043
TI  - Candidate protein markers for radiation biodosimetry in the hematopoietically
      humanized mouse model.
AB  - After a radiological incident, there is an urgent need for fast and reliable
      bioassays to identify radiation-exposed individuals within the first week post
      exposure. This study aimed to identify candidate radiation-responsive protein
      biomarkers in human lymphocytes in vivo using humanized NOD scid gamma (Hu-NSG)
      mouse model. Three days after X-irradiation (0-2 Gy, 88 cGy/min), human CD45+
      lymphocytes were collected from the Hu-NSG mouse spleen and quantitative changes
      in the proteome of the human lymphocytes were analysed by mass spectrometry.
      Forty-six proteins were differentially expressed in response to radiation
      exposure. FDXR, BAX, DDB2 and ACTN1 proteins were shown to have dose-dependent
      response with a fold change greater than 2. When these proteins were used to
      estimate radiation dose by linear regression, the combination of FDXR, ACTN1 and
      DDB2 showed the lowest mean absolute errors (<=0.13 Gy) and highest coefficients
      of determination (R2 = 0.96). Biomarker validation studies were performed in
      human lymphocytes 3 days after irradiation in vivo and in vitro. In conclusion,
      this is the first study to identify radiation-induced human protein signatures in
      vivo using the humanized mouse model and develop a protein panel which could be
      used for the rapid assessment of absorbed dose 3 days after radiation exposure.

PMID- 30202045
TI  - Suspected or known neonatal sepsis and neurodevelopmental delay by 5 years.
AB  - OBJECTIVE: Evaluate impact of known and suspected neonatal sepsis in the term and
      preterm infant on neurodevelopmental delay by 5 years. STUDY DESIGN: Included
      infants were born in 2009-2010 and followed for 5 years. Diagnostic codes and at
      least 5 days of antibiotic use identified suspected sepsis. Laboratory results
      confirmed known sepsis. Diagnostic codes stratified developmental delay by sub
      type. Logistic regression analysis determined odds of developmental delay for
      sepsis and suspected sepsis. RESULTS: Of 65,938 included infants, 190 had sepsis
      and 3449 had suspected sepsis. After adjustment for known developmental risk
      factors, sepsis and suspected sepsis were associated with increased risk for any
      developmental delay, (1.48 (1.05-2.09) and 1.09 (1.01-1.18)), respectively, and
      multiple developmental delay sub-types. CONCLUSION: Neonatal sepsis and suspected
      sepsis are associated with neurodevelopmental delay by 5 years of age.

PMID- 30202046
TI  - In-utero idiopathic ductal constriction: a prenatal manifestation of Alagille and
      Williams syndrome arteriopathy.
AB  - OBJECTIVE: Williams and Alagille syndromes are genetic disorders associated with
      pathologic arterial narrowing. We hypothesized that fetal idiopathic ductus
      arteriosus (DA) constriction may represent a prenatal manifestation of the
      arteriopathy associated with these syndromes. METHODS: Multi-institutional case
      series review of the pre- and postnatal medical records, echocardiograms, and
      genetic test results of fetuses presenting with idiopathic DA constriction.
      RESULTS: We identified four cases of idiopathic fetal DA constriction at 21-36
      weeks of gestation. All had right ventricular hypertension, dilation,
      hypertrophy, and dysfunction and either DA constriction or absence. All
      demonstrated progressive peripheral pulmonary artery stenosis after birth. Three
      met clinical diagnostic criteria for Alagille syndrome; two tested had
      confirmatory JAG1 mutations. One also developed supravalvar aortic stenosis after
      birth and was positive for 7q11.23 deletion (Williams syndrome). CONCLUSION: This
      is the first case series to suggest that idiopathic fetal DA constriction may be
      a prenatal manifestation of genetic arteriopathy.

PMID- 30202044
TI  - Gastric cancer may share genetic predisposition with esophageal squamous cell
      carcinoma in Chinese populations.
AB  - Many features are shared between esophageal cancer (EC) and gastric cancer (GC).
      This study aimed to explore whether known EC susceptibility loci are also
      important in the development of GC. A total of 21 genetic variants associated
      with EC in genome-wide association studies were evaluated with association of GC
      risk in 2631 cases and 4373 controls of Chinese ancestry. Single variant and
      weighted genetic scores (WGS) for esophageal squamous cell carcinoma (ESCC),
      esophageal adenocarcinoma (EAC), and overall EC were analyzed with GC risk,
      respectively. Genetic variants of rs2274223 in PLCE1 at 10q23.33 (per G allele:
      odds ratio (OR) = 1.26, 95% confidence interval (CI): 1.16-1.38, P = 6.51 * 10
      8), rs10052657 in PDE4D at 5q11.2 (per C allele: OR = 1.12, 95% CI: 1.01-1.25, P
      = 3.28 * 10-2) and rs671 in ALDH2 at 12q24.12 (per A-allele: OR = 0.83, 95% CI:
      0.75-0.91, P = 1.14 * 10-4) were significantly associated with GC risk. The
      combined effect of those three variants had stronger influence on GC risk (OR =
      1.31, 95% CI: 1.19-1.44, P = 2.34 * 10-8). High WGS of ESCC was also associated
      with increased risk of GC (P = 5.52 * 10-4 as a continuous variable) (trend test
      P = 2.71 * 10-4), whereas no statistically significant associations were observed
      between the WGS of EAC and GC risk (P = 0.66 as a continuous variable) (trend
      test P = 0.70). ESCC rather than EAC may share genetic susceptibility with GC.
      Genetic variants at 10q23.33, 5q11.2, and 12q24.12 may be useful as biomarkers to
      identify individuals with high risk for both ESCC and GC.

PMID- 30202047
TI  - Positive-allosteric modulation of the 5-HT2C receptor: implications for
      neuropsychopharmacology and neurotherapeutics.

PMID- 30202048
TI  - Antidepressant potential of metabotropic glutamate receptor mGlu2 and mGlu3
      negative allosteric modulators.

PMID- 30202050
TI  - A tension-mediated glycocalyx-integrin feedback loop promotes mesenchymal-like
      glioblastoma.
AB  - Glioblastoma multiforme (GBMs) are recurrent lethal brain tumours. Recurrent GBMs
      often exhibit mesenchymal, stem-like phenotypes that could explain their
      resistance to therapy. Analyses revealed that recurrent GBMs have increased
      tension and express high levels of glycoproteins that increase the bulkiness of
      the glycocalyx. Studies showed that a bulky glycocalyx potentiates integrin
      mechanosignalling and tissue tension and promotes a mesenchymal, stem-like
      phenotype in GBMs. Gain- and loss-of-function studies implicated integrin
      mechanosignalling as an inducer of GBM growth, survival, invasion and treatment
      resistance, and a mesenchymal, stem-like phenotype. Mesenchymal-like GBMs were
      highly contractile and expressed elevated levels of glycoproteins that expanded
      their glycocalyx, and they were surrounded by a stiff extracellular matrix that
      potentiated integrin mechanosignalling. Our findings suggest that there is a
      dynamic and reciprocal link between integrin mechanosignalling and a bulky
      glycocalyx, implying a causal link towards a mesenchymal, stem-like phenotype in
      GBMs. Strategies to ameliorate GBM tissue tension offer a therapeutic approach to
      reduce mortality due to GBM.

PMID- 30202051
TI  - Polarized microtubule dynamics directs cell mechanics and coordinates forces
      during epithelial morphogenesis.
AB  - Coordinated rearrangements of cytoskeletal structures are the principal source of
      forces that govern cell and tissue morphogenesis1,2. However, unlike for actin
      based mechanical forces, our knowledge about the contribution of forces
      originating from other cytoskeletal components remains scarce. Here, we establish
      microtubules as central components of cell mechanics during tissue morphogenesis.
      We find that individual cells are mechanically autonomous during early Drosophila
      wing epithelium development. Each cell contains a polarized apical non
      centrosomal microtubule cytoskeleton that bears compressive forces, whereby acute
      elimination of microtubule-based forces leads to cell shortening. We further
      establish that the Fat planar cell polarity (Ft-PCP) signalling pathway3,4
      couples microtubules at adherens junctions (AJs) and patterns microtubule-based
      forces across a tissue via polarized transcellular stability, thus revealing a
      molecular mechanism bridging single cell and tissue mechanics. Together, these
      results provide a physical basis to explain how global patterning of microtubules
      controls cell mechanics to coordinate collective cell behaviour during tissue
      remodelling. These results also offer alternative paradigms towards the interplay
      of contractile and protrusive cytoskeletal forces at the single cell and tissue
      levels.

PMID- 30202049
TI  - BAP1 links metabolic regulation of ferroptosis to tumour suppression.
AB  - The roles and regulatory mechanisms of ferroptosis (a non-apoptotic form of cell
      death) in cancer remain unclear. The tumour suppressor BRCA1-associated protein 1
      (BAP1) encodes a nuclear deubiquitinating enzyme to reduce histone 2A
      ubiquitination (H2Aub) on chromatin. Here, integrated transcriptomic, epigenomic
      and cancer genomic analyses link BAP1 to metabolism-related biological processes,
      and identify cystine transporter SLC7A11 as a key BAP1 target gene in human
      cancers. Functional studies reveal that BAP1 decreases H2Aub occupancy on the
      SLC7A11 promoter and represses SLC7A11 expression in a deubiquitinating-dependent
      manner, and that BAP1 inhibits cystine uptake by repressing SLC7A11 expression,
      leading to elevated lipid peroxidation and ferroptosis. Furthermore, we show that
      BAP1 inhibits tumour development partly through SLC7A11 and ferroptosis, and that
      cancer-associated BAP1 mutants lose their abilities to repress SLC7A11 and to
      promote ferroptosis. Together, our results uncover a previously unappreciated
      epigenetic mechanism coupling ferroptosis to tumour suppression.

PMID- 30202053
TI  - A 3D cell shape that enables tube formation.

PMID- 30202054
TI  - How AI technology can tame the scientific literature.

PMID- 30202052
TI  - Effects of Vaspin on Insulin Resistance in Rats and Underlying Mechanisms.
AB  - Insulin resistance (IR) is the main pathogenesis of metabolic syndrome and a
      shared pathophysiological change in conditions such as diabetes mellitus,
      adiposity, hypertension, and atherosclerosis. Visceral adipose tissue-derived
      serpin (Vaspin) is a newly discovered adipocytokine with insulin-sensitizing and
      anti-inflammatory effects. To examine if vaspin can improve insulin resistance in
      rats fed a high-fat diet via the insulin receptor substrate/phosphatidylinositol
      3 kinase/protein kinase B/glucose transport (IRS/PI3K/Akt/Glut) and inhibitory
      kappaB alpha/nuclear factor-kappa B (IkappaBalpha/NF-kappaB) signalling pathways,
      thirty male Sprague-Dawley (SD) rats were randomly divided into three groups: the
      normal control group (NC group, n = 10), high-fat diet group (HFD group, n = 10)
      and vaspin intervention group (HFD + vaspin group, n = 10). Results showed that
      intervention with vaspin significantly decreased fasting blood glucose (FBG) and
      fasting insulin (FINS) concentrations in HFD - fed rats without significantly
      affecting body weight or triglyceride (TG) or total cholesterol (TC) levels. The
      areas under the intraperitoneal glucose tolerance test (IPGTT) and the insulin
      tolerance test (ITT) curves were significantly decreased in HFD + vaspin group
      compared with the HFD group, and the glucose infusion rate (GIR) showed the same
      trends. Western blot, real-time polymerase chain reaction (RT-PCR) and
      immunofluorescence staining showed that vaspin could improve insulin resistance
      in liver, skeletal muscle and adipose tissue by activating the IRS/PI3K/Akt/Glut
      signalling pathway and inhibiting the IkappaBalpha/NF-kappaB signalling pathway.

PMID- 30202055
TI  - Don't forget people in the use of big data for development.

PMID- 30202056
TI  - Integrative detection and analysis of structural variation in cancer genomes.
AB  - Structural variants (SVs) can contribute to oncogenesis through a variety of
      mechanisms. Despite their importance, the identification of SVs in cancer genomes
      remains challenging. Here, we present a framework that integrates optical
      mapping, high-throughput chromosome conformation capture (Hi-C), and whole-genome
      sequencing to systematically detect SVs in a variety of normal or cancer samples
      and cell lines. We identify the unique strengths of each method and demonstrate
      that only integrative approaches can comprehensively identify SVs in the genome.
      By combining Hi-C and optical mapping, we resolve complex SVs and phase multiple
      SV events to a single haplotype. Furthermore, we observe widespread structural
      variation events affecting the functions of noncoding sequences, including the
      deletion of distal regulatory sequences, alteration of DNA replication timing,
      and the creation of novel three-dimensional chromatin structural domains. Our
      results indicate that noncoding SVs may be underappreciated mutational drivers in
      cancer genomes.

PMID- 30202057
TI  - Gut fungal dysbiosis correlates with reduced efficacy of fecal microbiota
      transplantation in Clostridium difficile infection.
AB  - Fecal microbiota transplantation (FMT) is effective in treating recurrent
      Clostridium difficile infection (CDI). Bacterial colonization in recipients after
      FMT has been studied, but little is known about the role of the gut fungal
      community, or mycobiota. Here, we show evidence of gut fungal dysbiosis in CDI,
      and that donor-derived fungal colonization in recipients is associated with FMT
      response. CDI is accompanied by over-representation of Candida albicans and
      decreased fungal diversity, richness, and evenness. Cure after FMT is associated
      with increased colonization of donor-derived fungal taxa in recipients.
      Recipients of successful FMT ("responders") display, after FMT, a high relative
      abundance of Saccharomyces and Aspergillus, whereas "nonresponders" and
      individuals treated with antibiotics display a dominant presence of Candida. High
      abundance of C. albicans in donor stool also correlates with reduced FMT
      efficacy. Furthermore, C. albicans reduces FMT efficacy in a mouse model of CDI,
      while antifungal treatment reestablishes its efficacy, supporting a potential
      causal relationship between gut fungal dysbiosis and FMT outcome.

PMID- 30202059
TI  - Three-photon imaging of mouse brain structure and function through the intact
      skull.
AB  - Optical imaging through the intact mouse skull is challenging because of skull
      induced aberrations and scattering. We found that three-photon excitation
      provided improved optical sectioning compared with that obtained with two-photon
      excitation, even when we used the same excitation wavelength and imaging system.
      Here we demonstrate three-photon imaging of vasculature through the adult mouse
      skull at >500-MUm depth, as well as GCaMP6s calcium imaging over weeks in
      cortical layers 2/3 and 4 in awake mice, with 8.5 frames per second and a field
      of view spanning hundreds of micrometers.

PMID- 30202058
TI  - COMRADES determines in vivo RNA structures and interactions.
AB  - The structural flexibility of RNA underlies fundamental biological processes, but
      there are no methods for exploring the multiple conformations adopted by RNAs in
      vivo. We developed cross-linking of matched RNAs and deep sequencing (COMRADES)
      for in-depth RNA conformation capture, and a pipeline for the retrieval of RNA
      structural ensembles. Using COMRADES, we determined the architecture of the Zika
      virus RNA genome inside cells, and identified multiple site-specific interactions
      with human noncoding RNAs.

PMID- 30202060
TI  - Terminal exon characterization with TECtool reveals an abundance of cell-specific
      isoforms.
AB  - Sequencing of RNA 3' ends has uncovered numerous sites that do not correspond to
      the termination sites of known transcripts. Through their 3' untranslated
      regions, protein-coding RNAs interact with RNA-binding proteins and microRNAs,
      which regulate many properties, including RNA stability and subcellular
      localization. We developed the terminal exon characterization (TEC) tool (
      http://tectool.unibas.ch ), which can be used with RNA-sequencing data from any
      species for which a genome annotation that includes sites of RNA cleavage and
      polyadenylation is available. We discovered hundreds of previously unknown
      isoforms and cell-type-specific terminal exons in human cells. Ribosome profiling
      data revealed that many of these isoforms were translated. By applying TECtool to
      single-cell sequencing data, we found that the newly identified isoforms were
      expressed in subpopulations of cells. Thus, TECtool enables the identification of
      previously unknown isoforms in well-studied cell systems and in rare cell types.

PMID- 30202063
TI  - Dynamics of cellular states of fibro-adipogenic progenitors during myogenesis and
      muscular dystrophy.
AB  - Fibro-adipogenic progenitors (FAPs) are currently defined by their anatomical
      position, expression of non-specific membrane-associated proteins, and ability to
      adopt multiple lineages in vitro. Gene expression analysis at single-cell level
      reveals that FAPs undergo dynamic transitions through a spectrum of cell states
      that can be identified by differential expression levels of Tie2 and Vcam1.
      Different patterns of Vcam1-negative Tie2high or Tie2low and Tie2low/Vcam1
      expressing FAPs are detected during neonatal myogenesis, response to acute injury
      and Duchenne Muscular Dystrophy (DMD). RNA sequencing analysis identified cell
      state-specific transcriptional profiles that predict functional interactions with
      satellite and inflammatory cells. In particular, Vcam1-expressing FAPs, which
      exhibit a pro-fibrotic expression profile, are transiently activated by acute
      injury in concomitance with the inflammatory response. Aberrant persistence of
      Vcam1-expressing FAPs is detected in DMD muscles or upon macrophage depletion,
      and is associated with muscle fibrosis, thereby revealing how disruption of
      inflammation-regulated FAPs dynamics leads to a pathogenic outcome.

PMID- 30202061
TI  - De novo assembly, characterization, functional annotation and expression patterns
      of the black tiger shrimp (Penaeus monodon) transcriptome.
AB  - The black tiger shrimp (Penaeus monodon) remains the second most widely cultured
      shrimp species globally; however, issues with disease and domestication have seen
      production levels stagnate over the past two decades. To help identify innovative
      solutions needed to resolve bottlenecks hampering the culture of this species, it
      is important to generate genetic and genomic resources. Towards this aim, we have
      produced the most complete publicly available P. monodon transcriptome database
      to date based on nine adult tissues and eight early life-history stages (BUSCO -
      Complete: 98.2% [Duplicated: 51.3%], Fragmented: 0.8%, Missing: 1.0%). The
      assembly resulted in 236,388 contigs, which were then further segregated into
      99,203 adult tissue specific and 58,678 early life-history stage specific
      clusters. While annotation rates were low (approximately 30%), as is typical for
      a non-model organisms, annotated transcript clusters were successfully mapped to
      several hundred functional KEGG pathways. Transcripts were clustered into groups
      within tissues and early life-history stages, providing initial evidence for
      their roles in specific tissue functions, or developmental transitions. We expect
      the transcriptome to provide an essential resource to investigate the molecular
      basis of commercially relevant-significant traits in P. monodon and other shrimp
      species.

PMID- 30202062
TI  - AIP1 and cofilin ensure a resistance to tissue tension and promote directional
      cell rearrangement.
AB  - In order to understand how tissue mechanics shapes animal body, it is critical to
      clarify how cells respond to and resist tissue stress when undergoing
      morphogenetic processes, such as cell rearrangement. Here, we address the
      question in the Drosophila wing epithelium, where anisotropic tissue tension
      orients cell rearrangements. We found that anisotropic tissue tension localizes
      actin interacting protein 1 (AIP1), a cofactor of cofilin, on the remodeling
      junction via cooperative binding of cofilin to F-actin. AIP1 and cofilin promote
      actin turnover and locally regulate the Canoe-mediated linkage between actomyosin
      and the junction. This mechanism is essential for cells to resist the mechanical
      load imposed on the remodeling junction perpendicular to the direction of tissue
      stretching. Thus, the present study delineates how AIP1 and cofilin achieve an
      optimal balance between resistance to tissue tension and morphogenesis.

PMID- 30202065
TI  - Cryovolcanism on the Earth: Origin of a Spectacular Crater in the Yamal Peninsula
      (Russia).
AB  - Geological activity on icy planets and planetoids includes cryovolcanism. Until
      recently, most research on terrestrial permafrost has been engineering-oriented,
      and many related phenomena have received too little attention. Although fast
      processes in the Earth's cryosphere were known before, they have never been
      attributed to cryovolcanism. The discovery of a couple of tens of meters wide
      crater in the Yamal Peninsula aroused numerous hypotheses of its origin,
      including a meteorite impact or migration of deep gas as a result of global
      warming. However, the origin of the Yamal crater can be explained in terms of
      cryospheric processes. Thus, the Yamal crater appears to result from collapse of
      a large pingo, which formed within a thaw lake when it shoaled and dried out
      allowing a large talik (that is layer or body of unfrozen ground in a permafrost
      area) below it to freeze back. The pingo collapsed under cryogenic hydrostatic
      pressure built up in the closed system of the freezing talik. This happened
      before the freezing completed, when a core of wet ground remained unfrozen and
      stored a huge amount of carbon dioxide dissolved in pore water. This eventually
      reached gas-phase saturation, and the resulting overpressure came to exceed the
      lithospheric confining stress and the strength of the overlying ice. As the pingo
      exploded, the demarcation of the crater followed the cylindrical shape of the
      remnant talik core.

PMID- 30202066
TI  - Laser guided ionic wind.
AB  - We report on a method to experimentally generate ionic wind by coupling an
      external large electric field with an intense femtosecond laser induced air
      plasma channel. The measured ionic wind velocity could be as strong as >4 m/s. It
      could be optimized by increasing the strength of the applied electric field and
      the volume of the laser induced plasma channel. The experimental observation was
      qualitatively confirmed by a numerical simulation of spatial distribution of the
      electric field. The ionic wind can be generated outside a high-voltage geometry,
      even at remote distances.

PMID- 30202067
TI  - Clerodane furanoditerpenoids as the probable cause of toxic hepatitis induced by
      Tinospora crispa.
AB  - Tinospora crispa is a popular traditional herbal plant commonly used throughout
      the world for treatment of various diseases, in particular type 2 diabetes
      mellitus. We report here a new case of toxic hepatitis in a 57-year old male
      patient in the French West Indies following the consumption of two aqueous
      extracts of fresh Tinospora crispa stems. It thus differs from two previously
      reported cases that concerned the chronic intake of powdered dry stems delivered
      in solid oral dosage forms (i.e. pellets and tablets). Liquid Chromatography
      Diode Array Detection-Mass Spectrometry (LC/DAD/MS) analyses were performed on an
      aqueous extract of the offending sample that mimics the swallowed preparation.
      They revealed the presence of species-specific molecular marker borapetoside C
      (1) and thus enabled an unambiguous phytochemical identification. The exploration
      of tandem MS/MS data obtained by ultra-high performance liquid
      chromatography/electrospray ionization quadrupole time-of-flight mass
      spectrometry (UHPLC-ESI-QTOF-HRMS) allowed the identification of 17 additional
      cis-clerodane-type furanoditerpenoid lactones, analogues of 1. These results
      support the hypothesis that the mechanisms underlying hepatotoxicity of Tinospora
      crispa are the same as those encountered with furanoditerpenoids-containing
      plants such as Teucrium chamaedrys or Dioscorea bulbifera. In the context of type
      2 diabetes treatment, we recommend that Tinospora crispa intake should be more
      closely monitored for signs of hepatotoxicity.

PMID- 30202064
TI  - A PECTIN METHYLESTERASE gene at the maize Ga1 locus confers male function in
      unilateral cross-incompatibility.
AB  - Unilateral cross-incompatibility (UCI) is a unidirectional inter/intra-population
      reproductive barrier when both parents are self-compatible. Maize Gametophyte
      factor1 (Ga1) is an intraspecific UCI system and has been utilized in breeding.
      However, the mechanism underlying maize UCI specificity has remained mysterious
      for decades. Here, we report the cloning of ZmGa1P, a pollen-expressed PECTIN
      METHYLESTERASE (PME) gene at the Ga1 locus that can confer the male function in
      the maize UCI system. Homozygous transgenic plants expressing ZmGa1P in a ga1
      background can fertilize Ga1-S plants and can be fertilized by pollen of ga1
      plants. ZmGa1P protein is predominantly localized to the apex of growing pollen
      tubes and may interact with another pollen-specific PME protein, ZmPME10-1, to
      maintain the state of pectin methylesterification required for pollen tube growth
      in Ga1-S silks. Our study discloses a PME-mediated UCI mechanism and provides a
      tool to manipulate hybrid breeding.

PMID- 30202069
TI  - Controlled state transfer in a Heisenberg spin chain by periodic drives.
AB  - The spin chain is a system that has been widely studied for its quantum phase
      transition. It also holds potential for practical application in quantum
      information, including quantum communication and quantum computation. In this
      paper, we propose a scheme for conditional state transfer in a Heisenberg XXZ
      spin chain. In our scheme, the absence or presence of a periodic driving
      potential results in either a perfect state transfer between the input and output
      ports, or a complete blockade at the input port. This scheme is formalized by
      deriving an analytical expression of the effective Hamiltonian for the spin chain
      subject to a periodic driving field in the high-frequency limit. The influence of
      the derivation of the optimal parameter on the performance of the state transfer
      is also examined, showing the robustness of the spin chain for state transfer. In
      addition, the collective decoherence effect on the fidelity of state transfer is
      discussed. The proposed scheme paves the way for the realization of integrated
      quantum logic elements, and may find application in quantum information
      processing.

PMID- 30202068
TI  - Deciphering the Odorant Binding, Activation, and Discrimination Mechanism of
      Dhelobp21 from Dastarus Helophoroides.
AB  - Odorant-binding proteins (OBPs) play a pivotal role in transporting odorants
      through the sensillar lymph of insect chemosensory sensilla and increasing the
      sensitivity of the olfactory system. To address the ligand binding, activation,
      and release mechanisms of OBPs, we performed a set of conventional molecular
      dynamics simulations for binding of the odorant-binding protein DhelOBP21 from
      Dastarcus helophoroides with 18 ligands (1-NPN and 17 volatiles), as well as four
      constant-pH molecular dynamics simulations. We found that the open pocket
      DhelOBP21 at pH 5.0 could bind volatiles and form a closed pocket complex via
      transformation of its N-terminus into regular Helix at pH 7.0 and vice versa.
      Moreover, the discrimination of volatiles (selectivity and promiscuity) was
      determined by the characteristics of both the volatiles and the 'essential' and
      'selective' amino acid residues in OBP binding pockets, rather than the binding
      affinity of the volatiles. This study put forward a new hypothesis that during
      the binding of volatiles there are two transitions for the DhelOBP21 amino
      terminus: pH- and odorant binding-dependent random-coil-to-helix. Another
      important finding is providing a framework for the exploration of the complete
      coil-to-helix transition process and theoretically analyzing its underlying
      causes at molecular level.

PMID- 30202071
TI  - Long-term outcome of flexible onabotulinum toxin A treatment in facial dystonia.
AB  - PURPOSE: The purpose of this study was to assess the long-term outcome of
      onabotulinum used to treat facial dystonia and compare a flexible and fixed
      treatment regimen. METHODS: This was a retrospective comparative study looking at
      benign essential blepharospasm (BEB), hemifacial spasm (HFS) and aberrant facial
      nerve regeneration synkinesis (AFR) treatment with onabotulinum toxin A
      (Botox(r)) over a minimum of 10 years. Fifty-one patients were recruited into the
      study, with each dystonia subgroup having 17 patients. Blepharospasm disability
      score (BDS), subjective improvement score (SIS), duration of maximal effect (DME)
      and complications were recorded at each visit. RESULTS: The mean age was 63 years
      and gender predominately female. Thirty-seven patients underwent flexible
      treatment intervals compared to 14 fixed treatment intervals, averaging 3.4 and 4
      per annum, respectively. Mean BDS significantly improved from 6 to 3 at last
      review across all 3 groups, with the highest effect on BEB. BDS improvement was
      greater in flexible intervals. SIS remained similar for all three conditions
      during follow-up, but in those undergoing flexible intervals, SIS increased by a
      small margin compared to fixed interval. Mean DME was 10.5 weeks across all
      dystonias, but increased progressively only in the flexible interval group.
      Complications included ptosis (30%), dry eye (14%) and lagophthalmos (8%).
      CONCLUSION: Flexible onabotulinum provided better long-term relief on BDS for
      facial dystonia than a fixed regimen. Flexible interval treatment may also
      provide better patient satisfaction and longer DME compared to fixed treatment.
      Both have similar complication rates. With flexible treatment however, fewer
      injections were required over 10 years, leading to cost saving.

PMID- 30202072
TI  - Which quadrant is less painful for intravitreal injection? A prospective study.
AB  - PURPOSE: To evaluate the relationship between injection site and pain severity
      following intravitreal injection of bevacizumab (IVB). DESIGN: Prospective,
      randomized, four-armed, clinical trial. METHODS: The present study was a
      prospective, randomized, four-armed clinical trial, which included 1004 eyes from
      1004 patients. Patients receiving IVB were randomly assigned into four groups:
      superotemporal (ST); superonasal (SN); inferotemporal (IT); and inferonasal (IN)
      injections. The visual analog scale (VAS) was used to assess pain. Primary study
      variables were the relationship between pain severity and injection site, number
      of previous injections, age, sex, and indication for injection. Secondary
      variables included best-corrected visual acuity (BCVA) and central macular
      thickness (CMT) changes 1 month post IVB. RESULTS: Overall mean pain score was
      2.86 +/- 2.2. Indications for injection were diabetic macular edema (84.1%),
      neovascular age-related macular degeneration (7.7%), and macular edema secondary
      to retinal vein occlusion (8.2%). The mean VAS scores in the SN, IN, ST, and IT
      groups were 1.5 +/- 1.7, 3 +/- 2.3, 4 +/- 2, and 3 +/- 2.1, respectively. Pain
      severity was significantly correlated with injection site (p < 0.001) and sex (p
      < 0.001); females showed higher pain scores. A negative correlation existed
      between pain score and number of previous injections (p = 0.03). Pain severity
      was not associated with age (p = 0.659), lens status (p = 0.478), vitreous reflux
      (p = 0.648), or indication for injection (p = 0.390). No significant
      complications were observed. CONCLUSIONS: ST quadrant was the most painful and SN
      quadrant was the least painful sites for IVB. Pain severity score was
      significantly associated with injection site, number of injections, and sex.

PMID- 30202070
TI  - Coordinate regulation of mutant NPC1 degradation by selective ER autophagy and
      MARCH6-dependent ERAD.
AB  - Niemann-Pick type C disease is a fatal, progressive neurodegenerative disorder
      caused by loss-of-function mutations in NPC1, a multipass transmembrane
      glycoprotein essential for intracellular lipid trafficking. We sought to define
      the cellular machinery controlling degradation of the most common disease-causing
      mutant, I1061T NPC1. We show that this mutant is degraded, in part, by the
      proteasome following MARCH6-dependent ERAD. Unexpectedly, we demonstrate that
      I1061T NPC1 is also degraded by a recently described autophagic pathway called
      selective ER autophagy (ER-phagy). We establish the importance of ER-phagy both
      in vitro and in vivo, and identify I1061T as a misfolded endogenous substrate for
      this FAM134B-dependent process. Subcellular fractionation of I1061T Npc1 mouse
      tissues and analysis of human samples show alterations of key components of ER
      phagy, including FAM134B. Our data establish that I1061T NPC1 is recognized in
      the ER and degraded by two different pathways that function in a complementary
      fashion to regulate protein turnover.

PMID- 30202073
TI  - A considerable fraction of soil-respired CO2 is not emitted directly to the
      atmosphere.
AB  - Soil CO2 efflux (Fsoil) is commonly considered equal to soil CO2 production
      (Rsoil), and both terms are used interchangeably. However, a non-negligible
      fraction of Rsoil can be consumed in the subsurface due to a host of disparate,
      yet simultaneous processes. The ratio between CO2 efflux/O2 influx, known as the
      apparent respiratory quotient (ARQ), enables new insights into CO2 losses from
      Rsoil not previously captured by Fsoil. We present the first study using
      continuous ARQ estimates to evaluate annual CO2 losses of carbon produced from
      Rsoil. We found that up to 1/3 of Rsoil was emitted directly to the atmosphere,
      whereas 2/3 of Rsoil was removed by subsurface processes. These subsurface losses
      are attributable to dissolution in water, biological activities and chemical
      reactions. Having better estimates of Rsoil is key to understanding the true
      influence of ecosystem production on Rsoil, as well as the role of soil CO2
      production in other connected processes within the critical zone.

PMID- 30202074
TI  - Influence of switching rule on motor learning.
AB  - Humans and animals can flexibly switch rules to generate the appropriate response
      to the same sensory stimulus, e.g., we kick a soccer ball toward a friend on our
      team, but we kick the ball away from a friend who is traded to an opposing team.
      Most motor learning experiments have relied on a fixed rule; therefore, the
      effects of switching rules on motor learning are unclear. Here, we study the
      availability of motor learning effects when a rule in the training phase is
      different from a rule in the probe phase. Our results suggest that switching a
      rule causes partial rather than perfect availability. To understand the neural
      mechanisms inherent in our results, we verify that a computational model can
      explain our experimental results when each neural unit has different activities,
      but the total population activity is the same in the same planned movement with
      different rules. Thus, we conclude that switching rules causes modulations in
      individual neural activities under the same population activity, resulting in a
      partial transfer of learning effects for the same planned movements. Our results
      indicate that sports training and rehabilitation should include various
      situations even when the same motions are required.

PMID- 30202075
TI  - Meaning Guides Attention during Real-World Scene Description.
AB  - Intelligent analysis of a visual scene requires that important regions be
      prioritized and attentionally selected for preferential processing. What is the
      basis for this selection? Here we compared the influence of meaning and image
      salience on attentional guidance in real-world scenes during two free-viewing
      scene description tasks. Meaning was represented by meaning maps capturing the
      spatial distribution of semantic features. Image salience was represented by
      saliency maps capturing the spatial distribution of image features. Both types of
      maps were coded in a format that could be directly compared to maps of the
      spatial distribution of attention derived from viewers' eye fixations in the
      scene description tasks. The results showed that both meaning and salience
      predicted the spatial distribution of attention in these tasks, but that when the
      correlation between meaning and salience was statistically controlled, only
      meaning accounted for unique variance in attention. The results support theories
      in which cognitive relevance plays the dominant functional role in controlling
      human attentional guidance in scenes. The results also have practical
      implications for current artificial intelligence approaches to labeling real
      world images.

PMID- 30202076
TI  - Transcriptome Analysis of Gossypium hirsutum L. Reveals Different Mechanisms
      among NaCl, NaOH and Na2CO3 Stress Tolerance.
AB  - As an important source of fiber and edible oil, cotton has great economic value.
      In comparison to their individual studies, association and differentiation
      between salt and alkaline tolerance has not been focused yet by scientists. We
      have used next-generation RNA-Seq technique to analyze transcriptional changes
      under salt and alkaline stresses in cotton. Overall, 25,929 and 6,564
      differentially expressed genes (DEGs) were identified in roots and leaves,
      respectively. Gene functional annotation showed that genes involving ionic
      homeostasis were significantly up-regulated under NaCl stress and Na2CO3 stress,
      and genes enriched in starch and sucrose metabolism were up-regulated under NaOH
      stress and Na2CO3 stress. Furthermore, a synergistic enhancing effect between
      NaCl and NaOH stress was also observed in this study. Likewise, our studies
      indicate further that genes related with starch and sucrose metabolism were
      regulated to respond to the high pH under Na2CO3 stress, inducing plant hormone
      signal transduction and key enzyme reactive oxygen species (ROS) activity to
      respond to ionic toxicity and intracellular ionic homeostasis. By analyzing the
      expression profiles of diverse tissues under different salt and alkaline
      stresses, this study provides valuable ideas for genetic improvements of cotton
      tolerance to salt-alkaline stress.

PMID- 30202078
TI  - Influence of internal climate variability on Indian Ocean Dipole properties.
AB  - The Indian Ocean Dipole (IOD) is the dominant mode of interannual variability
      over the tropical Indian Ocean (IO) and its future changes are projected to
      impact the climate and weather of Australia, East Africa, and Indonesia.
      Understanding the response of the IOD to a warmer climate has been largely
      limited to studies of individual coupled general circulation models or multi
      model ensembles. This has provided valuable insight into the IOD's projected
      response to increasing greenhouse gases but has limitations in accounting for the
      role of internal climate variability. Using the Community Earth System Model
      Large Ensemble (CESM-LE), the IOD is examined in thirty-five present-day and
      future simulations to determine how internal variability influences properties of
      the IOD and their response to a warmer climate. Despite small perturbations in
      the initial conditions as the only difference between ensemble members,
      significant relationships between the mean state of the IO and the IOD arise,
      leading to a spread in the projected IOD responses to increasing greenhouse
      gases. This is driven by the positive Bjerknes feedback, where small differences
      in mean thermocline depth, which are caused by internal climate variability,
      generate significant variations in IOD amplitude, skewness, and the
      climatological zonal sea surface temperature gradient.

PMID- 30202077
TI  - A soy protein Lunasin can ameliorate amyloid-beta 42 mediated neurodegeneration
      in Drosophila eye.
AB  - Alzheimer's disease (AD), a fatal progressive neurodegenerative disorder, also
      results from accumulation of amyloid-beta 42 (Abeta42) plaques. These Abeta42
      plaques trigger oxidative stress, abnormal signaling, which results in neuronal
      death by unknown mechanism(s). We misexpress high levels of human Abeta42 in the
      differentiating retinal neurons of the Drosophila eye, which results in the
      Alzheimer's like neuropathology. Using our transgenic model, we tested a soy
      derived protein Lunasin (Lun) for a possible role in rescuing neurodegeneration
      in retinal neurons. Lunasin is known to have anti-cancer effect and reduces
      stress and inflammation. We show that misexpression of Lunasin by transgenic
      approach can rescue Abeta42 mediated neurodegeneration by blocking cell death in
      retinal neurons, and results in restoration of axonal targeting from retina to
      brain. Misexpression of Lunasin downregulates the highly conserved cJun-N
      terminal Kinase (JNK) signaling pathway. Activation of JNK signaling can prevent
      neuroprotective role of Lunasin in Abeta42 mediated neurodegeneration. This
      neuroprotective function of Lunasin is not dependent on retinal determination
      gene cascade in the Drosophila eye, and is independent of Wingless (Wg) and
      Decapentaplegic (Dpp) signaling pathways. Furthermore, Lunasin can significantly
      reduce mortality rate caused by misexpression of human Abeta42 in flies. Our
      studies identified the novel neuroprotective role of Lunasin peptide, a potential
      therapeutic agent that can ameliorate Abeta42 mediated neurodegeneration by
      downregulating JNK signaling.

PMID- 30202080
TI  - Characteristics of Cadmium Sorption by Heat-Activated Red Mud in Aqueous
      Solution.
AB  - Red mud as a waste material is produced in large quantities by the aluminum
      industry. Heat activation has been used to enhance sorption capacity of red mud
      for its beneficial reuse as an effective sorbent. In this study, heat-activated
      red mud (HARM) was investigated for its Cd(II) sorption capacity under various
      process conditions (Cd concentration, pH and contact time) using response surface
      methodology (RSM). Analysis with RSM identified pH as the most important process
      parameter. The positive correlation between higher pH and greater Cd(II) sorption
      was likely due to: (i) decreased proton competition with Cd(II) for sorption
      sites at higher pH; (ii) enhanced sorption via ion exchange by monovalent Cd
      species from hydrolysis at higher pH; and (iii) improved thermodynamics of
      sorption at higher pH as protons are being released as products. Further analysis
      indicated the sorption process was thermodynamically favorable with a negative
      change in Gibbs free energy. Additionally, the sorption process exhibited a
      positive change in enthalpy, indicative of endothermic nature of sorption; this
      is consistent with sorption increase at higher temperature. These findings
      provide needed insight into the mechanisms underlying Cd(II) sorption by HARM for
      more effective applications of heat-activated red mud as sorbents for Cd(II)
      removal.

PMID- 30202079
TI  - Hypercapnia Alters Expression of Immune Response, Nucleosome Assembly and Lipid
      Metabolism Genes in Differentiated Human Bronchial Epithelial Cells.
AB  - Hypercapnia, the elevation of CO2 in blood and tissues, commonly occurs in severe
      acute and chronic respiratory diseases, and is associated with increased risk of
      mortality. Recent studies have shown that hypercapnia adversely affects innate
      immunity, host defense, lung edema clearance and cell proliferation. Airway
      epithelial dysfunction is a feature of advanced lung disease, but the effect of
      hypercapnia on airway epithelium is unknown. Thus, in the current study we
      examined the effect of normoxic hypercapnia (20% CO2 for 24 h) vs normocapnia (5%
      CO2), on global gene expression in differentiated normal human airway epithelial
      cells. Gene expression was assessed on Affymetrix microarrays, and subjected to
      gene ontology analysis for biological process and cluster-network representation.
      We found that hypercapnia downregulated the expression of 183 genes and
      upregulated 126. Among these, major gene clusters linked to immune responses and
      nucleosome assembly were largely downregulated, while lipid metabolism genes were
      largely upregulated. The overwhelming majority of these genes were not previously
      known to be regulated by CO2. These changes in gene expression indicate the
      potential for hypercapnia to impact bronchial epithelial cell function in ways
      that may contribute to poor clinical outcomes in patients with severe acute or
      advanced chronic lung diseases.

PMID- 30202081
TI  - Pharmacological difference between degrader and inhibitor against oncogenic BCR
      ABL kinase.
AB  - Chronic myelogenous leukemia (CML) is characterized by the oncogenic fusion
      protein, BCR-ABL protein kinase, against which clinically useful inhibitors have
      been developed. An alternative approach to treat CML is to degrade the BCR-ABL
      protein. Recently, potent degraders against BCR-ABL have been developed by
      conjugating dasatinib to ligands for E3 ubiquitin ligases. Since the degraders
      contain the dasatinib moiety, they also inhibit BCR-ABL kinase activity, which
      complicates our understanding of the impact of BCR-ABL degradation by degraders
      in CML growth inhibition. To address this issue, we chose DAS-IAP, as a potent
      BCR-ABL degrader, and developed a structurally related inactive degrader, DAS
      meIAP, which inhibits kinase activity but does not degrade the BCR-ABL protein.
      DAS-IAP showed slightly weaker activity than DAS-meIAP in inhibiting cell growth
      when CML cells were treated for 48 h. However, DAS-IAP showed sustained growth
      inhibition even when the drug was removed after short-term treatment, whereas CML
      cell growth rapidly resumed following removal of DAS-meIAP and dasatinib.
      Consistently, suppression of BCR-ABL levels and downstream kinase signaling were
      maintained after DAS-IAP removal, whereas kinase signaling rapidly recovered
      following removal of DAS-meIAP and dasatinib. These results indicate that BCR-ABL
      degrader shows more sustained inhibition of CML cell growth than ABL kinase
      inhibitor.

PMID- 30202082
TI  - Two-wavelength infrared responsive hydrogel actuators containing rare-earth
      photothermal conversion particles.
AB  - Two-wavelength infrared responsive soft actuators composed of rare-earth-oxide
      particles composited in a thermoresponsive hydrogel have been constructed.
      Because Nd2O3 and Yb2O3 particles possess independent narrow infrared adsorption
      at 808 and 980 nm, respectively, the vicinity of the particles in the gel can be
      individually heated by irradiation at each adsorption wavelength, inducing a
      local volume phase transition. The wavelength-selective volume phase transition
      can be controlled based on the combination of the particles incorporated in the
      gels and the wavelength of the irradiation laser at the optimized water
      temperature. Only the alternatively correct combinations successfully induced
      selective local clouding at the irradiation spots in the gel sheets. The original
      transparency of the gel was immediately recovered by turning off the light.
      Furthermore, rod-shaped block gels with Nd2O3 and Yb2O3 particles separately
      arranged on the left and right sides at the bottom of the rods were prepared to
      demonstrate wavelength-selective bending motion. The correct light combination
      caused reversible bending motion of only the side of the rod gel with the
      corresponding adsorbed particles.

PMID- 30202083
TI  - Global sea level change signatures observed by GRACE satellite gravimetry.
AB  - Ice mass loss on land results in sea level rise, but its rate varies regionally
      due to gravitational self-attraction effects. Observing regional sea level rates
      by ocean mass change using the Gravity Recovery and Climate Experiment (GRACE)
      gravity solutions is difficult due to GRACE's spatial resolution (~a few hundred
      km) and other limitations. Here we estimate regional sea level mass change using
      GRACE data (without contributions from temperature and salinity variations) by
      addressing these limitations: restoring spatially spread and attenuated signals
      in post-processed GRACE data; constraining ocean mass distribution to conform to
      the changing geoid; and judging specific corrections applied to GRACE data
      including a new geocenter estimate. The estimated global sea level mass trend for
      2003-2014 is 2.14 +/- 0.12 mm/yr. Regional trends differ considerably among ocean
      basins, ranging from -0.5 mm/yr in the Arctic to about 2.4 mm/yr in the Indian
      and South Atlantic Oceans.

PMID- 30202084
TI  - Is molecular evolution faster in the tropics?
AB  - The evolutionary speed hypothesis (ESH) suggests that molecular evolutionary
      rates are higher among species inhabiting warmer environments. Previously, the
      ESH has been investigated using small numbers of latitudinally-separated sister
      lineages; in animals, these studies typically focused on subsets of Chordata and
      yielded mixed support for the ESH. This study analyzed public DNA barcode
      sequences from the cytochrome c oxidase subunit I (COI) gene for six of the
      largest animal phyla (Arthropoda, Chordata, Mollusca, Annelida, Echinodermata,
      and Cnidaria) and paired latitudinally-separated taxa together informatically. Of
      8037 lineage pairs, just over half (51.6%) displayed a higher molecular rate in
      the lineage inhabiting latitudes closer to the equator, while the remainder
      (48.4%) displayed a higher rate in the higher-latitude lineage. To date, this
      study represents the most comprehensive analysis of latitude-related molecular
      rate differences across animals. While a statistically-significant pattern was
      detected from our large sample size, our findings suggest that the EHS may not
      serve as a strong universal mechanism underlying the latitudinal diversity
      gradient and that COI molecular clocks may generally be applied across latitudes.
      This study also highlights the merits of using automation to analyze large DNA
      barcode datasets.

PMID- 30202085
TI  - Antitumour activity of pembrolizumab in advanced mucosal melanoma: a post-hoc
      analysis of KEYNOTE-001, 002, 006.
AB  - BACKGROUND: Mucosal melanoma is an aggressive melanoma with poor prognosis. We
      assessed efficacy of pembrolizumab in patients with advanced mucosal melanoma in
      KEYNOTE-001 (NCT01295827), -002 (NCT01704287), and -006 (NCT01866319). METHODS:
      Patients received pembrolizumab 2 mg/kg every 3 weeks (Q3W) or 10 mg/kg Q2W or
      Q3W. Response was assessed by independent central review per RECIST v1.1.
      RESULTS: 1567 patients were treated and 84 (5%) had mucosal melanoma. Fifty-one
      of 84 were ipilimumab-naive. In patients with mucosal melanoma, the objective
      response rate (ORR) was 19% (95% CI 11-29%), with median duration of response
      (DOR) of 27.6 months (range 1.1 + to 27.6). Median progression-free survival
      (PFS) was 2.8 months (95% CI 2.7-2.8), with median overall survival (OS) of 11.3
      months (7.7-16.6). ORR was 22% (95% CI 11-35%) and 15% (95% CI 5-32%) in
      ipilimumab-naive and ipilimumab-treated patients. CONCLUSION: Pembrolizumab
      provides durable antitumour activity in patients with advanced mucosal melanoma
      regardless of prior ipilimumab.

PMID- 30202086
TI  - Excess body weight, weight gain and obesity-related cancer risk in women in
      Norway: the Norwegian Women and Cancer study.
AB  - BACKGROUND: Excess body weight and weight gain have been reported to
      independently increase the risk of several cancers. There are few published
      studies in nationally representative populations of women on specific, 'obesity
      related' cancers in relation to prior weight change and relevant confounders.
      METHODS: Based on self-reported anthropometry, we prospectively assessed body
      mass index (BMI), weight change over 6 years and subsequent obesity-related
      cancer risk in the Norwegian Women and Cancer study. We used Cox proportional
      hazard models to calculate hazard ratios and restricted cubic splines to model
      potential non-linear dose-response relationships. RESULTS: Excess body weight
      increased the risk of overall obesity-related cancer, postmenopausal breast,
      colorectal, colon, endometrial and kidney cancer, with endometrial cancer showing
      a threefold elevated risk. High weight gain ( >= 10 kg) increased the risk of
      overall obesity-related cancer, postmenopausal breast, endometrial and pancreatic
      cancer. The association between high weight gain and pancreatic cancer was
      strong, with 91% increased risk. CONCLUSIONS: Maintaining stable weight in middle
      adulthood, irrespective of BMI category at baseline, and avoiding excess body
      weight are both important in the prevention of several obesity-related cancers in
      women. Our finding of increased risk of pancreatic cancer in women with moderate
      and high weight gain is novel.

PMID- 30202087
TI  - Role of blood urea nitrogen in predicting the post-discharge prognosis in elderly
      patients with acute decompensated heart failure.
AB  - Blood urea nitrogen (BUN) is a surrogate marker for neurohormonal activation, but
      the association between BUN and the post-discharge prognosis in elderly patients
      with acute decompensated heart failure (ADHF) is not well defined. We explored
      the association between BUN and post-discharge all-cause mortality in 652 elderly
      patients (73.9 +/- 7.8 yr) with ADHF. All patients were followed for a mean
      duration of 32 months (12-69 months). BUN was analyzed both as a continuous
      variable and according to two categories: low BUN group (BUN < 15.35 mmol/L, N =
      361) and high BUN group (BUN >= 15.35 mmol/L, N = 291). The risk of all-cause
      mortality increased by 1.6% per 1 mmol/L increase in BUN concentration when BUN
      was used as a continuous variable [hazard ratio (HR): 1.016, 95% confidence
      interval (CI): 1.006-1.026, p = 0.002]. BUN maintained an independent and
      significant positive correlation with all-cause mortality as a categorical
      variable (HR: 1.355, 95% CI: 1.023-1.794, p = 0.034 for the high BUN group). The
      BUN C-statistic for predicting all-cause mortality was 0.624 (95% CI: 0.585
      0.661). The cut-off value for BUN was 15.35 mmol/L with sensitivity of 0.58 and
      specificity of 0.63. The prognostic performance of BUN was similar to brain
      natriuretic peptide (BNP) for predicting all-cause mortality (C-statistic: z =
      0.044, p = 0.965). These results suggest that BUN is an independent predictor of
      post-discharge all-cause mortality in elderly patients with ADHF and its
      prognostic performance was similar to that of BNP.

PMID- 30202089
TI  - Experimental and computational framework for a dynamic protein atlas of human
      cell division.
AB  - Essential biological functions, such as mitosis, require tight coordination of
      hundreds of proteins in space and time. Localization, the timing of interactions
      and changes in cellular structure are all crucial to ensure the correct assembly,
      function and regulation of protein complexes1-4. Imaging of live cells can reveal
      protein distributions and dynamics but experimental and theoretical challenges
      have prevented the collection of quantitative data, which are necessary for the
      formulation of a model of mitosis that comprehensively integrates information and
      enables the analysis of the dynamic interactions between the molecular parts of
      the mitotic machinery within changing cellular boundaries. Here we generate a
      canonical model of the morphological changes during the mitotic progression of
      human cells on the basis of four-dimensional image data. We use this model to
      integrate dynamic three-dimensional concentration data of many fluorescently
      knocked-in mitotic proteins, imaged by fluorescence correlation spectroscopy
      calibrated microscopy5. The approach taken here to generate a dynamic protein
      atlas of human cell division is generic; it can be applied to systematically map
      and mine dynamic protein localization networks that drive cell division in
      different cell types, and can be conceptually transferred to other cellular
      functions.

PMID- 30202090
TI  - A topological source of quantum light.
AB  - Quantum light is characterized by distinctive statistical distributions that are
      possible only because of quantum mechanical effects. For example, single photons
      and correlated photon pairs exhibit photon number distributions with variance
      lower than classically allowed limits. This enables high-fidelity transmission of
      quantum information and sensing with lower noise than possible with classical
      light sources1,2. Most quantum light sources rely on spontaneous parametric
      processes such as down-conversion and four-wave mixing2. These processes are
      mediated by vacuum fluctuations of the electromagnetic field. Therefore, by
      manipulating the electromagnetic mode structure, for example with dispersion
      engineered nanophotonic systems, the spectrum of generated photons can be
      controlled3-7. However, disorder, which is ubiquitous in nanophotonic
      fabrication, causes device-to-device spectral variations8-11. Here we realize
      topologically robust electromagnetic modes and use their vacuum fluctuations to
      create a quantum light source in which the spectrum of generated photons is much
      less affected by fabrication-induced disorder. Specifically, we use the
      topological edge states realized in a two-dimensional array of ring resonators to
      generate correlated photon pairs by spontaneous four-wave mixing and show that
      they outperform their topologically trivial one-dimensional counterparts in terms
      of spectral robustness. We demonstrate the non-classical nature of the generated
      light and the realization of a robust source of heralded single photons by
      measuring the conditional antibunching of photons, that is, the reduced
      likelihood of photons arriving together compared to thermal or laser light. Such
      topological effects, which are unique to bosonic systems, could pave the way for
      the development of robust quantum photonic devices.

PMID- 30202088
TI  - Tracing HIV-1 strains that imprint broadly neutralizing antibody responses.
AB  - Understanding the determinants of broadly neutralizing antibody (bNAb) evolution
      is crucial for the development of bNAb-based HIV vaccines1. Despite emerging
      information on cofactors that promote bNAb evolution in natural HIV-1 infections,
      in which the induction of bNAbs is genuinely rare2, information on the impact of
      the infecting virus strain on determining the breadth and specificity of the
      antibody responses to HIV-1 is lacking. Here we analyse the influence of viral
      antigens in shaping antibody responses in humans. We call the ability of a virus
      strain to induce similar antibody responses across different hosts its antibody
      imprinting capacity, which from an evolutionary biology perspective corresponds
      to the viral heritability of the antibody responses. Analysis of 53 measured
      parameters of HIV-1-binding and neutralizing antibody responses in a cohort of
      303 HIV-1 transmission pairs (individuals who harboured highly related HIV-1
      strains and were putative direct transmission partners or members of an HIV-1
      transmission chain) revealed that the effect of the infecting virus on the
      outcome of the bNAb response is moderate in magnitude but highly significant. We
      introduce the concept of bNAb-imprinting viruses and provide evidence for the
      existence of such viruses in a systematic screening of our cohort. The bNAb
      imprinting capacity can be substantial, as indicated by a transmission pair with
      highly similar HIV-1 antibody responses and strong bNAb activity. Identification
      of viruses that have bNAb-imprinting capacities and their characterization may
      thus provide the potential to develop lead immunogens.

PMID- 30202091
TI  - Extremely efficient terahertz high-harmonic generation in graphene by hot Dirac
      fermions.
AB  - Multiple optical harmonic generation-the multiplication of photon energy as a
      result of nonlinear interaction between light and matter-is a key technology in
      modern electronics and optoelectronics, because it allows the conversion of
      optical or electronic signals into signals with much higher frequency, and the
      generation of frequency combs. Owing to the unique electronic band structure of
      graphene, which features massless Dirac fermions1-3, it has been repeatedly
      predicted that optical harmonic generation in graphene should be particularly
      efficient at the technologically important terahertz frequencies4-6. However,
      these predictions have yet to be confirmed experimentally under technologically
      relevant operation conditions. Here we report the generation of terahertz
      harmonics up to the seventh order in single-layer graphene at room temperature
      and under ambient conditions, driven by terahertz fields of only tens of
      kilovolts per centimetre, and with field conversion efficiencies in excess of 10
      3, 10-4 and 10-5 for the third, fifth and seventh terahertz harmonics,
      respectively. These conversion efficiencies are remarkably high, given that the
      electromagnetic interaction occurs in a single atomic layer. The key to such
      extremely efficient generation of terahertz high harmonics in graphene is the
      collective thermal response of its background Dirac electrons to the driving
      terahertz fields. The terahertz harmonics, generated via hot Dirac fermion
      dynamics, were observed directly in the time domain as electromagnetic field
      oscillations at these newly synthesized higher frequencies. The effective
      nonlinear optical coefficients of graphene for the third, fifth and seventh
      harmonics exceed the respective nonlinear coefficients of typical solids by 7-18
      orders of magnitude7-9. Our results provide a direct pathway to highly efficient
      terahertz frequency synthesis using the present generation of graphene
      electronics, which operate at much lower fundamental frequencies of only a few
      hundreds of gigahertz.

PMID- 30202092
TI  - Coherent encoding of subjective spatial position in visual cortex and
      hippocampus.
AB  - A major role of vision is to guide navigation, and navigation is strongly driven
      by vision1-4. Indeed, the brain's visual and navigational systems are known to
      interact5,6, and signals related to position in the environment have been
      suggested to appear as early as in the visual cortex6,7. Here, to establish the
      nature of these signals, we recorded in the primary visual cortex (V1) and
      hippocampal area CA1 while mice traversed a corridor in virtual reality. The
      corridor contained identical visual landmarks in two positions, so that a purely
      visual neuron would respond similarly at those positions. Most V1 neurons,
      however, responded solely or more strongly to the landmarks in one position
      rather than the other. This modulation of visual responses by spatial location
      was not explained by factors such as running speed. To assess whether the
      modulation is related to navigational signals and to the animal's subjective
      estimate of position, we trained the mice to lick for a water reward upon
      reaching a reward zone in the corridor. Neuronal populations in both CA1 and V1
      encoded the animal's position along the corridor, and the errors in their
      representations were correlated. Moreover, both representations reflected the
      animal's subjective estimate of position, inferred from the animal's licks,
      better than its actual position. When animals licked in a given location-whether
      correctly or incorrectly-neural populations in both V1 and CA1 placed the animal
      in the reward zone. We conclude that visual responses in V1 are controlled by
      navigational signals, which are coherent with those encoded in hippocampus and
      reflect the animal's subjective position. The presence of such navigational
      signals as early as a primary sensory area suggests that they permeate sensory
      processing in the cortex.

PMID- 30202093
TI  - Author Correction: Structure and mechanogating mechanism of the Piezo1 channel.
AB  - In Extended Data Fig. 9a of this Article, the bottom micrographs of mPiezo1
      DeltaL3-4-IRES-GFP and mPiezo1-DeltaL7-8-IRES-GFP (labelled 'permeabilized') are
      inadvertently the same images. The corrected figure panels are shown in the
      accompanying Amendment.

PMID- 30202096
TI  - Urate transporter inhibitor lesinurad is a selective peroxisome proliferator
      activated receptor gamma modulator (sPPARgammaM) in vitro.
AB  - Gout is the most common arthritic disease in human but was long neglected and
      therapeutic options are not satisfying. However, with the recent approval of the
      urate transporter inhibitor lesinurad, gout treatment has experienced a major
      innovation. Here we show that lesinurad possesses considerable modulatory potency
      on peroxisome proliferator-activated receptor gamma (PPARgamma). Since gout has a
      strong association with metabolic diseases such as type 2 diabetes, this side
      activity appears as very valuable contributing factor to the clinical efficacy
      profile of lesinurad. Importantly, despite robustly activating PPARgamma in
      vitro, lesinurad lacked adipogenic activity, which seems due to differential
      coactivator recruitment and is characterized as selective PPARgamma modulator
      (sPPARgammaM).

PMID- 30202094
TI  - Runx2 is required for the proliferation of osteoblast progenitors and induces
      proliferation by regulating Fgfr2 and Fgfr3.
AB  - Runx2 and Sp7 are essential transcription factors for osteoblast differentiation.
      However, the molecular mechanisms responsible for the proliferation of osteoblast
      progenitors remain unclear. The early onset of Runx2 expression caused limb
      defects through the Fgfr1-3 regulation by Runx2. To investigate the physiological
      role of Runx2 in the regulation of Fgfr1-3, we compared osteoblast progenitors in
      Sp7-/- and Runx2-/- mice. Osteoblast progenitors accumulated and actively
      proliferated in calvariae and mandibles of Sp7-/- but not of Runx2-/- mice, and
      the number of osteoblast progenitors and their proliferation were dependent on
      the gene dosage of Runx2 in Sp7-/- background. The expression of Fgfr2 and Fgfr3,
      which were responsible for the proliferation of osteoblast progenitors, was
      severely reduced in Runx2-/- but not in Sp7-/- calvariae. Runx2 directly
      regulated Fgfr2 and Fgfr3, increased the proliferation of osteoblast progenitors,
      and augmented the FGF2-induced proliferation. The proliferation of Sp7-/-
      osteoblast progenitors was enhanced and strongly augmented by FGF2, and Runx2
      knockdown reduced the FGF2-induced proliferation. Fgfr inhibitor AZD4547
      abrogated all of the enhanced proliferation. These results indicate that Runx2 is
      required for the proliferation of osteoblast progenitors and induces
      proliferation, at least partly, by regulating Fgfr2 and Fgfr3 expression.

PMID- 30202095
TI  - Bioengineering functional smooth muscle with spontaneous rhythmic contraction in
      vitro.
AB  - Oriented smooth muscle layers in the intestine contract rhythmically due to the
      action of interstitial cells of Cajal (ICC) that serve as pacemakers of the
      intestine. Disruption of ICC networks has been reported in various intestinal
      motility disorders, which limit the quality and expectancy of life. A significant
      challenge in intestinal smooth muscle engineering is the rapid loss of function
      in cultured ICC and smooth muscle cells (SMC). Here we demonstrate a novel
      approach to maintain the function of both ICC and SMC in vitro. Primary
      intestinal SMC mixtures cultured on feeder cells seeded electrospun poly(3
      caprolactone) scaffolds exhibited rhythmic contractions with directionality for
      over 10 weeks in vitro. The simplicity of this system should allow for wide usage
      in research on intestinal motility disorders and tissue engineering, and may
      prove to be a versatile platform for generating other types of functional SMC in
      vitro.

PMID- 30202099
TI  - What tangled webs we weave.

PMID- 30202098
TI  - KIAA1199 promotes metastasis of colorectal cancer cells via microtubule
      destabilization regulated by a PP2A/stathmin pathway.
AB  - Tumor metastasis is the main cause of death in advanced colorectal cancer. Our
      previous research showed that upregulation of KIAA1199 predicted poorer outcomes,
      and promoted cell motility and tumor metastasis in colorectal cancer, with the
      mechanisms not being fully elucidated. Here, we demonstrate that silencing of
      KIAA1199 results in reduced tumor metastasis in the orthotopic transplantation
      tumor model of colorectal cancer. Importantly, we find that KIAA1199 interacts
      with protein phosphatase 2A (PP2A) through the C-terminal domain and increases
      phosphatase activity of PP2A, which is essential for KIAA1199-mediated cell
      motility. Moreover, we identify stathmin, a microtubule-destabilizing protein, as
      a downstream of KIAA1199-PP2A complex. KIAA1199-induced dephosphorylation of
      stathmin results in microtubule destabilization and leads to enhanced cell
      motility. Furthermore, a microtubule-stabilizing drug paclitaxel could prevent
      KIAA1199-induced microtubule destabilization, and inhibit cell migration and
      invasion in vitro and tumor metastasis in vivo in colorectal cancer.
      Collectively, our study reveals that KIAA1199 promotes metastasis of colorectal
      cancer cells via microtubule destabilization regulated by a PP2A/stathmin
      pathway, and suggests that KIAA1199 may be a promising target for preventing
      metastasis in colorectal cancer.

PMID- 30202097
TI  - Loss of solute carrier family 7 member 2 exacerbates inflammation-associated
      colon tumorigenesis.
AB  - Solute carrier family 7 member 2 (SLC7A2, also known as CAT2) is an inducible
      transporter of the semi-essential amino acid L-arginine (L-Arg), which has been
      implicated in wound repair. We have reported that both SLC7A2 expression and L
      Arg availability are decreased in colonic tissues from inflammatory bowel disease
      patients and that mice lacking Slc7a2 exhibit a more severe disease course when
      exposed to dextran sulfate sodium (DSS) compared to wild-type (WT) mice. Here, we
      present evidence that SLC7A2 plays a role in modulating colon tumorigenesis in
      the azoxymethane (AOM)-DSS model of colitis-associated carcinogenesis (CAC).
      SLC7A2 was localized predominantly to colonic epithelial cells in WT mice.
      Utilizing the AOM-DSS model, Slc7a2-/- mice had significantly increased tumor
      number, burden, and risk of high-grade dysplasia vs. WT mice. Tumors from Slc7a2
      /- mice exhibited significantly increased levels of the proinflammatory
      cytokines/chemokines IL-1beta, CXCL1, CXCL5, IL-3, CXCL2, CCL3, and CCL4, but
      decreased levels of IL-4, CXCL9, and CXCL10 compared to tumors from WT mice. This
      was accompanied by a shift toward pro-tumorigenic M2 macrophage activation in
      Slc7a2-deficient mice, as marked by increased colonic CD11b+F4/80+ARG1+ cells
      with no alteration in CD11b+F4/80+NOS2+ cells by flow cytometry and
      immunofluorescence microscopy. The shift toward M2 macrophage activation was
      confirmed in bone marrow-derived macrophages from Slc7a2-/- mice. In bone marrow
      chimeras between Slc7a2-/- and WT mice, the recipient genotype drove the CAC
      phenotype, suggesting the importance of epithelial SLC7A2 in abrogating
      neoplastic risk. These data reveal that SLC7A2 has a significant role in the
      protection from CAC in the setting of chronic colitis, and suggest that the
      decreased SLC7A2 in inflammatory bowel disease (IBD) may contribute to CAC risk.
      Strategies to enhance L-Arg availability by supplementing L-Arg and/or increasing
      L-Arg uptake could represent a therapeutic approach in IBD to reduce the
      substantial long-term risk of colorectal carcinoma.

PMID- 30202100
TI  - Gas-phase sugar formation using hydroxymethylene as the reactive formaldehyde
      isomer.
AB  - Carbohydrates (CH2O)n are the formal adducts of carbon (atoms) to water with a
      repeating unit that structurally resembles H-C-OH (hydroxymethylene). Although
      hydroxymethylene has been suggested as a building block for sugar formation, it
      is a reactive species that had escaped detection until recently. Here we
      demonstrate that formaldehyde reacts with its isomer hydroxymethylene to give
      glycolaldehyde in a nearly barrierless reaction. This carbonyl-ene-type
      transformation operates in the absence of base and solvent at cryogenic
      temperatures similar to those found in extraterrestrial environments or
      interstellar clouds. Hydroxymethylene acts as a building block for an iterative
      sugar synthesis, as we demonstrate through the formation of the triose
      glyceraldehyde. The thermodynamically preferred ketose dihydroxyacetone does not
      form, and the formation of further branched sugars in the iterative synthesis
      presented here is unlikely. The results therefore provide a link between the well
      known formose (Butlerow) reaction and sugar formation under non-aqueous
      conditions.

PMID- 30202101
TI  - Stereoselective synthesis of a composite knot with nine crossings.
AB  - The simultaneous synthesis of a molecular nine-crossing composite knot that
      contains three trefoil tangles of the same handedness and a [Formula: see text]
      link (a type of cyclic [3]catenane topologically constrained to always have at
      least three twists within the links) is reported. Both compounds contain high
      degrees of topological writhe (w = 9), a structural feature of supercoiled DNA.
      The entwined products are generated from the cyclization of a hexameric Fe(II)
      circular helicate by ring-closing olefin metathesis, with the mixture of
      topological isomers formed as a result of different ligand connectivity patterns.
      The metal-coordinated composite knot was isolated by crystallization, the
      topology unambiguously proven by tandem mass spectrometry, with X-ray
      crystallography confirming that the 324-atom loop crosses itself nine times with
      matching handedness (all Delta or all Lambda) at every metal centre within each
      molecule. Controlling the connectivity of the ligand end groups on circular metal
      helicate scaffolds provides an effective synthetic strategy for the
      stereoselective synthesis of composite knots and other complex molecular
      topologies.

PMID- 30202102
TI  - Easy as one, two, three.

PMID- 30202103
TI  - Formation of the layered conductive magnet CrCl2(pyrazine)2 through redox-active
      coordination chemistry.
AB  - The unique properties of graphene, transition-metal dichalcogenides and other two
      dimensional (2D) materials have boosted interest in layered coordination solids.
      In particular, 2D materials that behave as both conductors and magnets could find
      applications in quantum magnetoelectronics and spintronics. Here, we report the
      synthesis of CrCl2(pyrazine)2, an air-stable layered solid, by reaction of CrCl2
      with pyrazine (pyz). This compound displays a ferrimagnetic order below ~55 K,
      reflecting the presence of strong magnetic interactions. Electrical conductivity
      measurements demonstrate that CrCl2(pyz)2 reaches a conductivity of 32 mS cm-1 at
      room temperature, which operates through a 2D hopping-based transport mechanism.
      These properties are induced by the redox-activity of the pyrazine ligand, which
      leads to a smearing of the Cr 3d and pyrazine pi states. We suggest that the
      combination of redox-active ligands and reducing paramagnetic metal ions
      represents a general approach towards tuneable 2D materials that consist of
      charge-neutral layers and exhibit both long-range magnetic order and high
      electronic conductivity.

PMID- 30202104
TI  - Chromopynones are pseudo natural product glucose uptake inhibitors targeting
      glucose transporters GLUT-1 and -3.
AB  - The principles guiding the design and synthesis of bioactive compounds based on
      natural product (NP) structure, such as biology-oriented synthesis (BIOS), are
      limited by their partial coverage of the NP-like chemical space of existing NPs
      and retainment of bioactivity in the corresponding compound collections. Here we
      propose and validate a concept to overcome these limitations by de novo
      combination of NP-derived fragments to structurally unprecedented 'pseudo natural
      products'. Pseudo NPs inherit characteristic elements of NP structure yet enable
      the efficient exploration of areas of chemical space not covered by NP-derived
      chemotypes, and may possess novel bioactivities. We provide a proof of principle
      by designing, synthesizing and investigating the biological properties of
      chromopynone pseudo NPs that combine biosynthetically unrelated chromane- and
      tetrahydropyrimidinone NP fragments. We show that chromopynones define a glucose
      uptake inhibitor chemotype that selectively targets glucose transporters GLUT-1
      and -3, inhibits cancer cell growth and promises to inspire new drug discovery
      programmes aimed at tumour metabolism.

PMID- 30202105
TI  - Author Correction: Amine hemilability enables boron to mechanistically resemble
      either hydride or proton.
AB  - During the revision of this Article prior to publication, a computational study
      was reported (Vallejos, M. M. & Pellegrinet, S. C. Theoretical study of the BF3
      promoted rearrangement of oxiranyl N-methyliminodiacetic acid boronates. J. Org.
      Chem. 82, 5917-5925; 2017) that evaluates the nucleophilic boryl transfer
      mechanism predicted in this Article; this reference has now been added as number
      19, and the subsequent references renumbered.

PMID- 30202106
TI  - Sub-wavelength terahertz imaging through optical rectification.
AB  - We record a sub-wavelength terahertz image of a caster sugar grain thanks to
      optical rectification in the sample excited with a femtosecond laser beam. The
      lateral spatial resolution of this technique is given by the laser spot size at
      the sample and here its measured value is 50 MUm, i.e. ~lambda/12. We give an
      estimation of the ultimate resolution that could be achieved with this method.

PMID- 30202107
TI  - Generation and assembly of human brain region-specific three-dimensional
      cultures.
AB  - The ability to generate region-specific three-dimensional (3D) models to study
      human brain development offers great promise for understanding the nervous system
      in both healthy individuals and patients. In this protocol, we describe how to
      generate and assemble subdomain-specific forebrain spheroids, also known as brain
      region-specific organoids, from human pluripotent stem cells (hPSCs). We describe
      how to pattern the neural spheroids toward either a dorsal forebrain or a ventral
      forebrain fate, establishing human cortical spheroids (hCSs) and human subpallial
      spheroids (hSSs), respectively. We also describe how to combine the neural
      spheroids in vitro to assemble forebrain assembloids that recapitulate the
      interactions of glutamatergic and GABAergic neurons seen in vivo. Astrocytes are
      also present in the human forebrain-specific spheroids, and these undergo
      maturation when the forebrain spheroids are cultured long term. The initial
      generation of neural spheroids from hPSCs occurs in <1 week, with regional
      patterning occurring over the subsequent 5 weeks. After the maturation stage,
      brain region-specific spheroids are amenable to a variety of assays, including
      live-cell imaging, calcium dynamics, electrophysiology, cell purification, single
      cell transcriptomics, and immunohistochemistry studies. Once generated, forebrain
      spheroids can also be matured for >24 months in culture.

PMID- 30202108
TI  - Comparative phylogenetic methods and the cultural evolution of medicinal plant
      use.
AB  - Human life depends on plant biodiversity and the ways in which plants are used
      are culturally determined. Whilst anthropologists have used phylogenetic
      comparative methods (PCMs) to gain an increasingly sophisticated understanding of
      the evolution of political, religious, social and material culture, plant use has
      been almost entirely neglected. Medicinal plants are of special interest because
      of their role in maintaining people's health across the world. PCMs in
      particular, and cultural evolutionary theory in general, provide a framework in
      which to study the diversity of medicinal plant applications cross-culturally,
      and to infer changes in plant use over time. These methods can be applied to
      single medicinal plants as well as the entire set of plants used by a culture for
      medicine, and they account for the non-independence of data when testing for
      floristic, cultural or other drivers of plant use. With cultural, biological and
      linguistic diversity under threat, gaining a deeper and broader understanding of
      the variation of medicinal plant use through time and space is pressing.

PMID- 30202109
TI  - Molecularly thin two-dimensional hybrid perovskites with tunable optoelectronic
      properties due to reversible surface relaxation.
AB  - Due to their layered structure, two-dimensional Ruddlesden-Popper perovskites
      (RPPs), composed of multiple organic/inorganic quantum wells, can in principle be
      exfoliated down to few and single layers. These molecularly thin layers are
      expected to present unique properties with respect to the bulk counterpart, due
      to increased lattice deformations caused by interface strain. Here, we have
      synthesized centimetre-sized, pure-phase single-crystal RPP perovskites
      (CH3(CH2)3NH3)2(CH3NH3)n-1PbnI3n+1 (n = 1-4) from which single quantum well
      layers have been exfoliated. We observed a reversible shift in excitonic energies
      induced by laser annealing on exfoliated layers encapsulated by hexagonal boron
      nitride. Moreover, a highly efficient photodetector was fabricated using a
      molecularly thin n = 4 RPP crystal, showing a photogain of 105 and an internal
      quantum efficiency of ~34%. Our results suggest that, thanks to their dynamic
      structure, atomically thin perovskites enable an additional degree of control for
      the bandgap engineering of these materials.

PMID- 30202110
TI  - Decoupling the role of stress and corrosion in the intergranular cracking of
      noble-metal alloys.
AB  - Intergranular stress-corrosion cracking (IGSCC) is a form of environmentally
      induced crack propagation causing premature failure of elemental metals and
      alloys. It is believed to require the simultaneous presence of tensile stress and
      corrosion; however, the exact nature of this synergy has eluded experimental
      identification. For noble metal alloys such as Ag-Au, IGSCC is a consequence of
      dealloying corrosion, forming a nanoporous gold layer that is believed to have
      the ability to transmit cracks into grain boundaries in un-dealloyed parent phase
      via a pure mechanical process. Here using atomic-scale techniques and statistical
      characterizations for this alloy system, we show that the separate roles of
      stress and anodic dissolution can be decoupled and that the apparent synergy
      exists owing to rapid time-dependent morphology changes at the dealloyed
      layer/parent phase interface. We discuss the applicability of our findings to the
      IGSCC of important engineering Fe- and Ni-based alloys in critical applications.

PMID- 30202111
TI  - A multicaloric cooling cycle that exploits thermal hysteresis.
AB  - The giant magnetocaloric effect, in which large thermal changes are induced in a
      material on the application of a magnetic field, can be used for refrigeration
      applications, such as the cooling of systems from a small to a relatively large
      scale. However, commercial uptake is limited. We propose an approach to magnetic
      cooling that rejects the conventional idea that the hysteresis inherent in
      magnetostructural phase-change materials must be minimized to maximize the
      reversible magnetocaloric effect. Instead, we introduce a second stimulus,
      uniaxial stress, so that we can exploit the hysteresis. This allows us to lock-in
      the ferromagnetic phase as the magnetizing field is removed, which drastically
      removes the volume of the magnetic field source and so reduces the amount of
      expensive Nd-Fe-B permanent magnets needed for a magnetic refrigerator. In
      addition, the mass ratio between the magnetocaloric material and the permanent
      magnet can be increased, which allows scaling of the cooling power of a device
      simply by increasing the refrigerant body. The technical feasibility of this
      hysteresis-positive approach is demonstrated using Ni-Mn-In Heusler alloys. Our
      study could lead to an enhanced usage of the giant magnetocaloric effect in
      commercial applications.

PMID- 30202112
TI  - Compositional and orientational control in metal halide perovskites of reduced
      dimensionality.
AB  - Reduced-dimensional metal halide perovskites (RDPs) have attracted significant
      attention in recent years due to their promising light harvesting and emissive
      properties. We sought to increase the systematic understanding of how RDPs are
      formed. Here we report that layered intermediate complexes formed with the
      solvent provide a scaffold that facilitates the nucleation and growth of RDPs
      during annealing, as observed via in situ X-ray scattering. Transient absorption
      spectroscopy of RDP single crystals and films enables the identification of the
      distribution of quantum well thicknesses. These insights allow us to develop a
      kinetic model of RDP formation that accounts for the experimentally observed size
      distribution of wells. RDPs exhibit a thickness distribution (with sizes that
      extend above n = 5) determined largely by the stoichiometric proportion between
      the intercalating cation and solvent complexes. The results indicate a means to
      control the distribution, composition and orientation of RDPs via the selection
      of the intercalating cation, the solvent and the deposition technique.

PMID- 30202113
TI  - Author Correction: Efficient electrical detection of mid-infrared graphene
      plasmons at room temperature.
AB  - In the version of this Article originally published, the units of the right-hand
      y axis of Fig. 2a were incorrectly labelled as mS; they should have been uS.
      Also, the x-axis tick marks of Fig. 3b should have been aligned with Fig. 3a,c.
      These have now been corrected.

PMID- 30202115
TI  - High-throughput ovarian follicle counting by an innovative deep learning
      approach.
AB  - The evaluation of the number of mouse ovarian primordial follicles (PMF) can
      provide important information about ovarian function, regulation of
      folliculogenesis or the impact of chemotherapy on fertility. This counting,
      usually performed by specialized operators, is a tedious, time-consuming but
      indispensable procedure.The development and increasing use of deep machine
      learning algorithms promise to speed up and improve this process. Here, we
      present a new methodology of automatically detecting and counting PMF, using
      convolutional neural networks driven by labelled datasets and a sliding window
      algorithm to select test data. Trained from a database of 9 millions of images
      extracted from mouse ovaries, and tested over two ovaries (3 millions of images
      to classify and 2 000 follicles to detect), the algorithm processes the digitized
      histological slides of a completed ovary in less than one minute, dividing the
      usual processing time by a factor of about 30. It also outperforms the
      measurements made by a pathologist through optical detection. Its ability to
      correct label errors enables conducting an active learning process with the
      operator, improving the overall counting iteratively. These results could be
      suitable to adapt the methodology to the human ovarian follicles by transfer
      learning.

PMID- 30202114
TI  - Analyzing protein topology based on Laguerre tessellation of a pore-traversing
      water network.
AB  - Given the tight relation between protein structure and function, we present a set
      of methods to analyze protein topology, implemented in the VLDP program, relying
      on Laguerre space partitions built from series of molecular dynamics snapshots.
      The Laguerre partition specifies inter-atomic contacts, formalized in graphs. The
      deduced properties are the existence and count of water aggregates, possible
      passage ways and constrictions, the structure, connectivity, stability and depth
      of the water network. As a test-case, the membrane protein FepA is investigated
      in its full environment, yielding a more precise description of the protein
      surface. Inside FepA, the solvent splits into isolated clusters and an intricate
      network connecting both sides of the lipid bilayer. The network is dynamic,
      connections set on and off, occasionally substantially relocating traversing
      paths. Subtle differences are detected between two forms of FepA, ligand-free and
      complexed with its natural iron carrier, the enterobactin. The complexed form has
      more constricted and more centered openings in the upper part whereas, in the
      lower part, constriction is released: two main channels between the plug and
      barrel lead directly to the periplasm. Reliability, precision and the variety of
      topological features are the main interest of the method.

PMID- 30202117
TI  - Glucose dysregulation phenotypes - time to improve outcomes.

PMID- 30202116
TI  - Radial trunk-centred reference frame in haptic perception.
AB  - The shape of objects is typically identified through active touch. The accrual of
      spatial information by the hand over time requires the continuous integration of
      tactile and movement information. Sensory inputs arising from one single sensory
      source gives rise to an infinite number of possible touched locations in space.
      This observation raises the question of the determination of a common reference
      frame that might be employed by humans to resolve spatial ambiguity. Here, we
      employ a paradigm where observers reconstruct the spatial attributes of a
      triangle from tactile inputs applied to a stationary hand correlated with the
      voluntary movements of the other hand. We varied the orientation of the hands
      with respect to one another and to the trunk, and tested three distinct
      hypotheses regarding a reference frame used for integration: a hand-centred, a
      trunk-centred or an allocentric reference frame. The results indicated strongly
      that the integration of movement information and tactile inputs was performed in
      a radial trunk-centred reference frame.

PMID- 30202118
TI  - A Remember/Know Examination of Free-recall Reveals Dissociative Roles of Item-
      and Context-Information over Time.
AB  - It is well-established that the ability to freely recall information is driven by
      the extent to which the context at encoding is reinstated at retrieval. Still,
      when asked to judge the subjective quality of one's memories giving Remember/Know
      (R/K) judgments, people tend to classify a substantial proportion of recalls as
      being devoid of context. We suggest that R- and K-recalls differ with regard to
      their reliance on context- and item-information, with R-recalls driven primarily
      by contextual-information (e.g., associations evoked by the study-items) and K
      recalls driven primarily by information pertaining to the items (e.g., semantic
      information). Memory was tested both immediately after study and in a final free
      recall test conducted ~20 minutes after encoding-a timescale which is akin to
      real-life events. In line with our predictions, as compared to K-recalls, R
      recalls show stronger contextual effects, but similarly strong item-related
      effects over these timescales. Furthermore, drawing on theories regarding the
      forgetting of item- and contextual information, we hypothesized and found that R-
      and K-recalls are differentially affected by the passage of time. Our findings
      provide several converging pieces of evidence for differential roles of item and
      contextual information in driving recall and thus highlight the need to extend
      longstanding theories of free-recall to account for cases in which recall relies
      less on context.

PMID- 30202119
TI  - Studying the integrated functional cognitive basis of sustained attention with a
      Primed Subjective-Illusory-Contour Attention Task.
AB  - Sustained attention plays an important role in everyday life, for work, learning,
      or when affected by attention disorders. Studies of the neural correlates of
      attention commonly treat sustained attention as an isolated construct, measured
      with computerized continuous performance tests. However, in any ecological
      context, sustained attention interacts with other executive functions and depends
      on lower level perceptual processing. Such interactions occur, for example, in
      inhibition of interference, and processing of complex hierarchical stimuli; both
      of which are important for successful ecological attention. Motivated by the need
      for more studies on neural correlates of higher cognition, I present an
      experiment to investigate these interactions of attention in 17 healthy
      participants measured with high-resolution electroencephalography. Participants
      perform a novel 2-alternative forced-choice computerised performance test, the
      Primed Subjective Illusory Contour Attention Task (PSICAT), which presents
      gestalt-stimuli targets with distractor primes to induce interference inhibition
      during complex-percept processing. Using behavioural and brain-imaging analyses,
      I demonstrate the novel result that task-irrelevant incongruency can evoke
      stronger behavioural and neural responses than the task-relevant stimulus
      condition; a potentially important finding in attention disorder research. PSICAT
      is available as an open-source code repository at the following url, allowing
      researchers to reuse and adapt it to their requirements.
      https://github.com/zenBen/Kanizsa_Prime/ .

PMID- 30202121
TI  - No benefit of MitraClip for secondary mitral regurgitation in heart failure.

PMID- 30202120
TI  - Sex-specific patterns of gene expression following influenza vaccination.
AB  - Sex-based variations in the immune response to the influenza vaccines was
      reported, however, the genetic basis responsible for the sex variations in the
      immune response toward the influenza vaccines remains unclear. Here, the genes
      responsible for sex-specific responses after vaccination with trivalent
      inactivated influenza virus were identified. These genes were enriched in virus
      response pathways, especially interferon signaling. A list of genes showing
      different responses to the vaccine between females and males were obtained next.
      Our results demonstrated that females generate stronger immune responses to
      seasonal influenza vaccines within 24 hours than males. However, most of these
      genes with variability between sexes had the opposite expression levels after
      three days, suggesting that males retained the immune responses longer than
      female. To summary, our study identified genes responsible for the sex variations
      toward influenza vaccination. Our findings might provide insights into the
      development of the sex-dependent influenza vaccines.

PMID- 30202122
TI  - Neuroimaging in rheumatic diseases.

PMID- 30202123
TI  - Computed tomography with a stomach protocol and virtual gastroscopy in the
      staging of gastric cancer: an initial experience.
AB  - Objective: To evaluate the accuracy of multidetector computed tomography with a
      stomach protocol in staging of gastric cancer. Materials and Methods: We
      evaluated 14 patients who underwent computed tomography in a 16-channel scanner
      for preoperative staging of gastric adenocarcinoma between September 2015 and
      December 2016. All images were analyzed by the same radiologist, who had
      extensive experience in abdominal cancer imaging. The sensitivity, specificity,
      and accuracy of the method were calculated by comparing it with the pathology
      result. All patients underwent partial or total gastrectomy. Results: The mean
      age was 61.5 years, and 53.8% of the patients were male. The gastric lesions were
      classified as T1/T2 in 35.7% of the cases, as T3 in 28.5%, and as T4 in 35.7%.
      Eleven patients (68.7%) had suspicious (N positive) lymph nodes. The accuracy of
      the T1/T2, T3, T4, and lymph node staging tests was 85%, 78%, 90%, and 78%,
      respectively. The respective sensitivity and specificity values were 71% and 100%
      for T1/T2, 66% and 81% for T3, 100% and 90% for T4, and 88% and 60% for lymph
      nodes. Conclusion: Multidetector computed tomography with a stomach protocol,
      used in conjunction with virtual gastroscopy, shows good accuracy in the tumor
      and lymph node staging of gastric adenocarcinoma.

PMID- 30202124
TI  - Prevalence of pancreatic cystic neoplasms on imaging exams: association with
      signs of malignancy risk.
AB  - Objective: To analyze the prevalence of cystic lesions of the pancreas on imaging
      exams and their association with signs of malignancy risk. Materials and methods:
      This was an observational cross-sectional study, in which we evaluated 924
      sequential computed tomography and magnetic resonance imaging scans of the
      abdomen. For all of the patients included in the study, we reviewed the
      demographic data available in the medical records and evaluated the images.
      Results: Cysts were observed in 4.5% of patients, the prevalence of cysts being
      highest (7.6%) in patients over 60 years of age. Lesions were detected at higher
      rates on magnetic resonance imaging and in patients with pancreatic symptoms
      (6.1% and 42.9%, respectively). Signs of malignancy risk were observed in 26.3%
      of the patients, more frequently in those who were male and over 60 years of age.
      Conclusion: The prevalence of pancreatic cysts was 4.5%. Signs of malignancy risk
      were observed in 26.3% of the cystic neoplasms identified.

PMID- 30202125
TI  - Prognostic value of focal scintigraphic findings in clinically suspected cases of
      tibial stress fracture.
AB  - Objective: To investigate the correlation between tracer uptake on bone
      scintigraphy and recovery time in patients with tibial stress fracture. Materials
      and Methods: We evaluated two groups of athletes: those with clinical suspicion
      and a radiological diagnosis of tibial stress fracture (TSF group, n = 21); and
      those with no symptoms or evidence of fracture (control group, n = 10). All
      subjects underwent bone scintigraphy and magnetic resonance imaging with a
      maximum interval of 7 days between the assessments. Results: Using the region of
      interest technique, we obtained a quantitative evaluation index, comparing
      affected and unaffected legs. The mean uptake of 99mTc-MDP was significantly
      higher in the TSF group than in the control group (2.54 +/- 0.77 vs. 1.05 +/-
      0.11; p < 0.001). Conclusion: In our sample of athletes, determining the bone
      scintigraphy uptake indices provided an objective method to estimate the
      appropriate recovery time after a tibial stress fracture.

PMID- 30202126
TI  - Minimally invasive treatment of complex collections: safety and efficacy of
      recombinant tissue plasminogen activator as an adjuvant to percutaneous drainage.
AB  - Objective: To analyze the efficacy of recombinant tissue plasminogen activator (r
      TPA) injection in the evolution of percutaneous drainage of thick collections.
      Materials and Methods: This was a single-center study involving the retrospective
      analysis of hospitalized patients undergoing percutaneous drainage of thick
      (superficial or intracavitary) fluid collections, followed by injection of a
      fibrinolytic agent (r-TPA) into the affected space. Results: A total of 53
      percutaneous drainage procedures, with r-TPA injection, were performed in 51
      patients. Abdominal and pelvic collections were the most common, being seen in 38
      (73%) of the procedures; in 35 (66%), the etiology of the collection was
      attributed to postoperative complications. A total of 61 catheters were used in
      order to drain the 53 collections. Of those 61 catheters, 52 (85%) were large (12
      16 Fr) and 9 (15%) were small (4-10 Fr). The mean r-TPA dose was 5.7
      mg/collection per day, and the mean time from r-TPA injection to drain removal
      was 7.7 days. Percutaneous drainage in combination with r-TPA injection was
      successful in 96% of the cases. None of the patients showed coagulation changes
      during the study period. Conclusion: The use of once-daily, low-dose r-TPA for up
      to three consecutive days, as an adjunct to percutaneous drainage of thick
      collections, with or without loculation, appears to be an effective technique.

PMID- 30202127
TI  - Extravasation of iodinated contrast medium in cancer patients undergoing computed
      tomography.
AB  - Objective: The aim of this study was to evaluate the incidence of extravasation
      of iodinated contrast medium (ICM) at the site of intravenous injection in
      oncology patients submitted to computed tomography (CT). Materials and Methods:
      This was a retrospective, descriptive, single-center study that evaluated all
      patients who underwent CT with ICM administration and presented ICM
      extravasation, at a cancer center, between January 2010 and December 2015.
      Results: During the study period, we evaluated a total of 99,076 ICM injections
      and identified 199 cases of extravasation, the incidence rate therefore being
      0.20%. Among the patients who presented extravasation, the mean age was 59.22
      years and 60% were female. The extravasation was classified as mild in 94.10% of
      the patients and as moderate in 5.90%. There were no cases of severe
      extravasation in the sample. Conclusion: The incidence of ICM extravasation in
      cancer patients submitted to CT in the present study was similar to that reported
      for the general population, according to other studies in the literature. The
      vast majority of cases of extravasation were considered mild, and no severe cases
      were observed in the study sample.

PMID- 30202128
TI  - Facebook as a tool to promote radiology education: expanding from a local
      community of medical students to all of South America.
AB  - Objective: To assess the feasibility of Facebook to promote a radiology education
      project and to expand it from our university community of medical students to a
      wider audience. Materials and Methods: A group of 12 medical students created a
      Facebook page in June 2015, to contribute to radiology education in our
      university. From August 2015, clinical cases, including a brief explanation of
      clinical findings, along with different imaging modalities, were posted weekly
      and subscribers were encouraged to choose the most appropriate diagnosis. All
      cases were followed by the appropriate answer and an explanation to highlight
      imaging findings and diagnosis. Aiming to reach a larger audience, we also shared
      cases to a public Latin-American Facebook group, comprising a collective total of
      28,182 physicians and medical students. Using the Facebook Insights tracking
      tool, we prospectively analyzed subscriber interaction with our page for 14
      months. Results: During the period analyzed, 35 cases were posted. The most
      common imaging modalities were X-ray (n = 15) and computed tomography (n = 13).
      Before we began posting the weekly cases, our page had 286 likes. By October
      2016, that number had grown to 4244, corresponding to an increase of 1484% and
      eight times the size of the medical student community at our institution (n =
      530). Medical students made up most (76%) of the subscribers, followed by
      radiology residents (6%). An excellent or moderate contribution to personal image
      interpretation skills was reported by 65.3% and 33.1% of the users, respectively.
      Conclusion: Creating a Facebook page and posting weekly clinical cases proved to
      be an effective method of promoting radiology education.

PMID- 30202129
TI  - Small but troublesome: accessory ossicles with clinical significance.
AB  - Accessory ossicles are supernumerary and inconstant structures that are not
      caused by fractures. Derived from unfused ossification centers, accessory
      ossicles were first described by Vesalius in 1543. For centuries, they were
      believed to be asymptomatic. However, with advances in radiology techniques, many
      have been associated with painful syndromes. Although the original descriptions
      date from the sixteenth century, the subject is little discussed and, in some
      cases, controversial. The objective of this study was to describe the
      radiological aspects of a series of accessory ossicles and to review the
      evolution of their various descriptions, in order to revive discussion of the
      subject.

PMID- 30202130
TI  - Ultrasound evaluation of the penis.
AB  - Ultrasound is an excellent method for the study of penis. In this article, using
      a critical review of the literature and teaching files, we present examples of
      the major findings in the ultrasound routine, focusing on trauma, priapism,
      Peyronie's disease, and erectile dysfunction.

PMID- 30202131
TI  - Spectrum of central nervous system involvement in rheumatic diseases: pictorial
      essay.
AB  - The rheumatic diseases, which include systemic lupus erythematosus, rheumatoid
      arthritis, Behcet's disease, scleroderma, and ankylosing spondylitis, are
      characterized by involvement of connective tissue, with multiple manifestations.
      In those diseases, there can be involvement of the peripheral or central nervous
      system, and that involvement can be primary, presenting as a major feature of the
      clinical presentation, or secondary, as an effect of the drugs used in order to
      control a given disease or its complications. Knowledge of the wide variety of
      imaging findings is crucial to the diagnosis of a rheumatic disease, especially
      in the early stages, enabling effective treatment and minimizing disability. This
      pictorial essay, presenting cases from the records of two tertiary teaching
      hospitals, encompasses cases of patients diagnosed with rheumatic disease and
      illustrates the neuroradiological findings on magnetic resonance imaging and
      computed tomography, in order to emphasize the importance of these methods for
      properly diagnosing rheumatic diseases.

PMID- 30202132
TI  - Pneumorrhachis as a complication of bronchial asthma: computed tomography
      findings.

PMID- 30202133
TI  - Poorly differentiated large-cell neuroendocrine carcinoma of the paranasal sinus.

PMID- 30202134
TI  - Differential diagnosis of pathological intracranial calcifications in patients
      with microcephaly related to congenital Zika virus infection.

PMID- 30202135
TI  - Intraventricular ganglioglioma with dissemination of cerebrospinal fluid.

PMID- 30202136
TI  - Malformation of the brainstem accompanied by cortical dysplasia.

PMID- 30202137
TI  - Pediatric ovarian torsion: a diagnostic challenge.

PMID- 30202138
TI  - Asymptomatic apical aneurysm of the left ventricle with intracavitary thrombus: a
      diagnosis missed by echocardiography.

PMID- 30202139
TI  - Bouveret syndrome and its imaging diagnosis.

PMID- 30202140
TI  - Stress fracture and osteomyelitis in a patient with systemic lupus erythematosus.

PMID- 30202141
TI  - Incidental pancreatic cyst: still a lot of road to cover.

PMID- 30202142
TI  - Connectedness to family, school, peers, and community in socially vulnerable
      adolescents.
AB  - Youth who feel connected to people and institutions in their communities may be
      buffered from other risk factors in their lives. As a result, increasing
      connectedness has been recommended as a prevention strategy. In this study, we
      examined connectedness among 224 youth (ages 12-15), recruited from an urban
      medical emergency department, who were at elevated risk due to bullying
      perpetration or victimization, or low social connectedness. Regression analyses
      examined multiple domains of connectedness (family, school, peer, community) in
      relation to adjustment. Youth who felt more connected to parents reported lower
      levels of depressive symptoms, suicidal ideation, non-suicidal self-injury, and
      conduct problems, higher self-esteem and more adaptive use of free time. Youth
      who felt more connected to their school reported lower levels of depressive
      symptoms, suicidal ideation, social anxiety, and sexual activity, as well as
      higher levels of self-esteem and more adaptive use of free time. Community
      connectedness was associated with less social anxiety but more sexual activity,
      and peer connectedness was not related to youth adjustment in this unique sample.
      Findings suggest that family and school connectedness may buffer youth on a
      trajectory of risk, and may therefore be important potential targets for early
      intervention services.

PMID- 30202143
TI  - Elevation of fibrin degradation product (FDP) values prevents the negative
      conversion of serum CRP values after total knee arthroplasty.
AB  - Background: It is essential as an orthopedic surgeon to diagnose prosthetic joint
      infection (PJI) at an early stage and to carry out precise treatment as well as
      preventing the deterioration of functional prognosis as much as possible. We
      suspected that PJI might have been caused because the negative conversion of
      creatinine reactive protein (CRP) has been prolonged after total knee
      arthroplasty (TKA) and patients with no serum CRP negative conversion have been
      treated with antibiotics to avoid the morbidity of PJI. The purpose of the
      present study is to investigate the factors associated with prolongation of the
      negative conversion of CRP, with the exclusion of PJI patients. Methods: We
      performed a retrospective case control study at our institution from August 2014
      to August 2016. We classified the patients into two groups based on whether it
      required >=20 days (Group A, n = 23) or <20 days (Group B, n = 23) for CRP levels
      to normalize. Serum D-Dimer and fibrin degradation product (FDP) values were
      measured at 1, 2, 5, 9, 12, 16, 19, 23, 26, and 30 days after TKA. Exclusion
      criteria include anticoagulant oral administration cases before TKA, venous
      thromboembolism (VTE) by postoperative lower limb venous echocardiography before
      and after TKA, CRP re-elevation cases, and patients with PJI. The cutoff points
      for D-dimer and FDP levels for screening tests were calculated from the receiver
      operating characteristic (ROC) curve. Results: The ROC analysis of D- Dimer
      values at 30 days after TKA yielded an AUC of 0.891 (95% confidence interval (CI)
      0.858-1.000), which indicates nearly an excellent test. The cutoff point of 22.1
      MUg/dl for FDP value (Younden Index: 22.1 MUg/dl) showed a sensitivity of 81.8%
      (95% CI 70.1-92.8) and a specificity of 80.0% (95% CI 67.9-89.1). Conclusion: We
      revealed that CRP values of patient with an FDP level >=22.1 MUg/dl at 30 days
      after TKA necessarily showed negative conversion without antibiotic
      administration, when examining a patient with elevated serum CRP of minor
      criteria in the definition of PJI proposed by MSIS (other criteria do not apply).
      Level of evidence: III.

PMID- 30202144
TI  - Association of GDF-5 rs143383 polymorphism with radiographic defined knee
      osteoarthritis: A systematic review and meta-analysis.
AB  - Objective: To assess the association of GDF-5 rs143383 polymorphism with
      radiographic defined knee osteoarthritis (OA), a systematic review and meta
      analysis was conducted. Methods: A total of 17 relevant case-control studies with
      7424 cases and 11,310 controls was collected from several electronic databases up
      to June 2018. Results: The pooled results showed that GDF-5 rs143383 polymorphism
      was significantly associated with radiographic defined knee OA in overall and
      stratified analysis by ethnicity, source of controls and genotyping techniques.
      Conclusions: The GDF-5 rs143383 polymorphism might be used as a relevant risk
      estimate for radiographic defined Knee OA.

PMID- 30202145
TI  - Traumatic spinal cord injuries.

PMID- 30202146
TI  - A return to nature - The futility of surgery for burst fractures.

PMID- 30202147
TI  - Will 3D printing take away surgical planning from doctors?

PMID- 30202148
TI  - Publication trends and knowledge mapping in 3D printing in orthopaedics.
AB  - Purpose: Three dimensional (3D) printing, also called 'rapid prototyping' and
      'additive manufacturing' is considered as a "second industrial revolution." With
      this rapidly emerging technology, CT or MR images are used for the creation of
      graspable objects from 3D reconstituted images. Patient-specific anatomical
      models can be, therefore, manufactured efficiently. These can enhance surgeon's
      understanding of their patients' patho-anatomy and also help in precise
      preoperative planning. The 3D printed patient-specific guides can also help in
      achieving accurate bony cuts, precise implant placement, and nice surgical
      results. Customized implants, casts, orthoses and prosthetics can be created to
      match an individual patient's anatomy. The 3D printing of individualized
      artificial cartilage scaffolds and 3D bioprinting are some other areas of growing
      interest. We aim to study the publication trends in 3D printing as applied to the
      field of orthopaedics. Materials and methods: A literature search was performed
      to extract all papers related to 3D printing applications in orthopaedics and
      allied sciences on the Pubmed, Web of Science and SCOPUS databases. Suitable
      keywords and boolean operators ("3D Printing" OR "3-dimensional printing" OR "3D
      printed" OR "additive manufacturing" OR "rapid prototyping") AND (''Orthopaedics"
      OR "Orthopaedics'') were used, in May 2018. Search was attempted in Cochrane
      Database of Systematic Reviews, Cochrane Central Register of Controlled Trials,
      and Database of Abstracts of Review of Effectiveness (DARE) databases, using
      keywords 3d printing orthopaedics. A similar search was repeated in pubmed and
      SCOPUS to get more specific papers.No limits were set on the period or evidence
      level, as 3D printing in orthopaedics is relatively new and evidence available is
      usually limited to low-level studies. Trends in a publication on these topics
      were analyzed, focussing on publications, type of research (basic science or
      clinical), type of publication, authors, institution, and country. Some citations
      received by these papers were also analyzed in SCOPUS and Web of Science. MS
      Excel (2008 - Mac version) and VOS Viewer1.6.8 (2018- Mac version) software were
      used to analyze the search results and for citation mapping respectively. We also
      identified top 10 most cited articles in the field. Results: An increasing trend
      in publications in 3D printing-related work in orthopedic surgery and related
      fields was observed in the recent past. A search on Pubmed using the above
      strategy revealed 389 documents. A similar search revealed 653 documents on
      SCOPUS, many (314) of which were from an engineering background and only 271 were
      related to medicine. No papers were found in the Cochrane database. Search on
      TRIP database revealed 195 papers. A similar search revealed 237 papers on
      orthopedic applications on Pubmed and 269 documents on SCOPUS, whereas a search
      on Web of Science revealed only 23 papers. Publication trends were then analyzed
      on data derived from SCOPUS database. Overall, most papers were published from
      China, followed by United States, United Kingdom, and India. Conclusion: There
      has been an upsurge of interest in 3D printing in orthopedic surgery, as is
      evident by an increasing trend in research and publications in this area in the
      recent years. Presently, 3D printing is in a primitive stage in the field of
      orthopedic surgery as our knowledge is still insufficient, and costs and learning
      curve are somewhat high. However, looking at latest publication trends, we are
      enthusiastic that it holds the key to future in orthopaedics and trauma cases.

PMID- 30202149
TI  - Additive manufacturing applications in orthopaedics: A review.
AB  - The applications of Additive Manufacturing (AM) have increased extensively in the
      area of orthopaedics. The AM applications are for making anatomic models,
      surgical instruments & tool design, splints, implants and prosthesis. A brief
      review of various research articles shows that patient-specific orthopaedic
      procedures provide multiple applications areas and provide directions for future
      developments. The purpose of this paper is to identify the best possible usage of
      additive manufacturing applications in orthopaedics field. It also presents the
      steps used to prepare a 3D printed model by using this technology and details
      applications in the field of orthopaedics. AM gives a flexible solution in
      orthopaedics area, where customised implants can be formed as per the required
      shape and size and can help substitution with customised products. A 3D model
      created by this technology gain an accurate perception of patient's anatomy which
      is used to perform mock surgeries and is helpful for highly complex surgical
      pathologies. It makes surgeon's job accessible and increases the success rate of
      the operation. AM provides a perfect fit implant for the specific patient by
      unlimited geometric freedom. Various scanning technologies capture the status of
      bone defects, and printing of the model is done with the help of this technology.
      It gives an exact generation of a physical model which is also helpful for
      medical education, surgical planning and training. This technology can help to
      solve present-day challenges as data of every patient is different from another.

PMID- 30202150
TI  - 3D printing- creating a blueprint for the future of orthopedics: Current concept
      review and the road ahead!
AB  - The use of 3D printing in Orthopedics is set to transform the way surgeries are
      planned and executed. The development of X rays and later the CT scan and MRI
      enabled surgeons to understand the anatomy and condition better and helped plan
      surgeries on images obtained. 3DGraphy a term used for 3D printed orthopedic
      patient models and Jigs has gone a step further by providing surgeons with a
      physical copy of the patient's affected part that can not only be seen but also
      felt and moved around spatially. Similarly 3D printed Jigs are patient specific
      devices that are used to ensure optimal screw trajectory and implant placement
      with minimal exposure. While the use of 3D printed models and Jigs have now
      become routine, a similar revolution is happening in the field of designing and
      printing patient specific implants. Metal printing along with enhanced capability
      to print other biocompatible materials like PEEK and PLA is likely to improve the
      current implant manufacturing process. On the horizon is another interesting
      development related to this field - 3D Bio printing. Printing human tissues and
      organs is considered the final frontier and impressive strides have been made in
      printing bone graft substitutes and cartilage like material. This paper is an
      overview of all the current developments and the road ahead in this invigorating
      field.

PMID- 30202151
TI  - Role of CT and MRI in the design and development of orthopaedic model using
      additive manufacturing.
AB  - Objective: To study the role of Computed tomography (CT) and Magnetic resonance
      imaging (MRI) for design and development of orthopaedic model using additive
      manufacturing (AM) technologies. Methods: A significant number of research papers
      in this area are studied to provide the direction of development along with the
      future scope. Results: Briefly discussed various steps used to create a 3D model
      by Additive Manufacturing using CT and MRI scan. These scanning technologies are
      used to produce medical as well as orthopaedic implants by using AM technologies.
      The images so produced are exported in different software like OsiriX Imaging
      Software, 3D slicer, Mimics, Magics, 3D doctor and InVesalius to produce a 3D
      digital model. Various criteria's achieved by CT and MRI scan for design and
      development of orthopaedic implant using additive manufacturing are also
      discussed briefly. AM model created by this process show exact shape, size,
      dimensions, textures, colour and features. Conclusion: AM technologies help to
      convert the digital model into a 3D physical object, thereby improving the
      understanding of patient anatomy for treatment as well as for educational
      purpose. These scanning technologies have various applications to enhance the AM
      in the field of orthopaedic. In orthopaedic every patient model is a customised
      unit, sourced from the individual patient. 3D CAD data captured by these scanning
      technologies are directly exported in standard triangulate language (STL) format
      for printing by AM technologies. Crossestion of the physical model fabricated by
      this process shows a patient's anatomy if the model prepared by using the bone
      like material.

PMID- 30202152
TI  - Current status of 3D printing in spine surgery.
AB  - Three-dimensional printing (3DP) is one of the latest tools in the armamentarium
      of the modern spine surgeon. The yearning to be more precise and reliable whilst
      operating on the spine has led to an interest in this technology which has
      claimed to achieve these goals. 3D printing has been used pre-operatively for
      surgical planning and for resident or patient education. It has also found its
      way to the operation theatre where it is used to fabricate customized surgical
      tools or patient-specific implants. Several authors have highlighted significant
      benefits when 3D printing is used for specific indications in spine surgery.
      Novel applications of this technology in spine surgery have also been described
      and though still in a nascent stage, these are important for this technology to
      sustain itself in the future. However, major limitations have also come to light
      with this technology in use. This article seeks to review the current status and
      applications of 3D printing in spinal surgery and its major drawbacks while
      briefly describing the essentials of the technology. It is imperative that the
      modern spine surgeon knows about this important innovation and when and how it
      can be applied to improve surgical outcomes.

PMID- 30202153
TI  - Cervical pedicle screw guiding jig, an innovative solution.
AB  - Pedicle screws are one the commonest used modality in spinal instrumentation.
      However, the method of pedicle screw fixation in cervical spine as compared to
      thoracic and lumbar spine is still technically demanding because it carries the
      risk of catastrophic damage to the surrounding neurovascular structures We have
      utilized virtual planning and 3D (3-dimension) printing to develop a patient
      specific jig to guide the accurate placement of pedicle screws. A patient with
      bifacetal dislocation C7 over D1 classified as flexion-distraction injury type 3
      who was planned for decompression and fusion by posterior instrumentation at C6,
      C7, D1 and D2 was selected. A CT scan with 1 mm cuts was used to produce DICOM
      images of the same. Using these DICOM images virtual planning was done on MIMICS
      and 3 MATICS software to create patient specific jigs. These jigs were then 3D
      printed using a 3D printer and used for accurate placement of pedicle screws
      intra-operatively after adequate sterilization. Our procedure is low cost but
      high technology based. It is simple, accurate, and very cost effective. The
      technology transfer is very easy and can be adopted easily.

PMID- 30202154
TI  - Three dimensional scapular prints for evaluating glenoid morphology: An
      exploratory study.
AB  - Background: Computerised Tomography (CT) scans are conventionally employed to
      assess the glenoid morphology prior to total shoulder arthroplasty (TSA). This
      study explores the role of three-dimensional (3D) models for assessing glenoid
      morphology. Methods: CT scans of 32 patients scheduled for TSA were reconstructed
      to scapular models using customised software and a desktop 3D printer. The size
      and aspect ratios were maintained. Glenoid version, glenoid maximum height and
      width, and the maximum acromion antero-posterior (AP) length were compared
      between the models and CT scans. Results: The models were an accurate qualitative
      reflection of scapular anatomy. The average retroversion in 3D models was 8.19
      degrees +/-30.8 degrees  compared to 10.26 degrees +/-42.5 degrees  in scan
      images. The mean difference was 2.07 degrees +/-24.6 degrees  (p=0.408). However,
      the mean absolute error was 5.02 degrees +/-12.3 degrees . The mean difference of
      the glenoid maximum width and the acromion maximum AP length was 0.22+/-3.33mm
      (p=0.862) and 0.32+/-14.12mm (p=0.213) respectively. However, the mean difference
      was significant for the glenoid maximum height measuring 3.67+/-12.04mm with
      p=0.004. The correlation between the examiners was high for all parameters, with
      intraclass correlation ranging between 0.94 and 0.99. Conclusion: 3D printing
      technology promises to be a useful tool for preoperative planning with accurate
      reproduction of transverse plane anatomy. 3D prints represent superior definition
      of reconstructed anatomical measures such as glenoid height as compared to
      conventional CT Scans.

PMID- 30202155
TI  - 3D printing in designing of anatomical posterior column plate.
AB  - Background: Acetabulum has a complex anatomy due to which anatomical acetabular
      plates are still under developmental phase. Although intra-operative contouring
      of reconstruction plate is done as a standard practice, it is associated with
      increased operative time and morbidity of patient. We have designed an acetabular
      plate for posterior fixation from experience of previous studies performed in our
      institute on acetabular fracture fixation which should be appropriate for most of
      the patient of Indian origin. Apart from avoiding intra-operative contouring of
      acetabular plates it also helps in preventing intra articular screw penetration.
      Methods: We selected five consecutive patients with acetabular fracture needed to
      be operated from posterior approach and designed patient specific plate template
      from virtual surgical planning and 3D printing. These plate templates were then
      matched with our acetabular plate design and were used intra-operatively. Many
      parameters were assessed to evaluate accuracy of our plate design in those five
      patients. Result: All the plate templates appear to match our designed plate and
      no intra-operative contouring was required with our plate design. Conclusion:
      This was a pilot study and we need a large sample size to study accuracy of our
      acetabular plate design which might avoid intra-operative contouring, decreasing
      morbidity of patient and prevent wastage of resources in pre-operative planning
      and computer designing.

PMID- 30202156
TI  - Application of three dimensional printing in surgery for cam type of femoro
      acetabular impingement.
AB  - Surgical treatment of femoroacetabular impingement (FAI) focuses on improving the
      clearance for hip motion and alleviation of femoral abutment against the
      acetabular rim. Cam type of impingement is managed by performing an
      osteochondroplasty to remove the excess impinging bone from the head neck
      junction, thus improving the head neck offset. This procedure can be done by safe
      surgical dislocation, arthroscopy assisted mini-open method or all arthroscopy
      technique. Whatever be the approach, adequate excision of the Cam deformity is
      necessary to avoid suboptimal results. Under-excision leads to persistent
      symptoms and progression of disease, while over-excision can lead to weak bone
      vulnerable to fracture or disturb the labral seal. Various techniques utilized
      for intra-operative evaluation of amount of excision required described in
      literature are fluoroscopy, spherometer gauges, intra-operative Computed
      Tomography (CT) scan, navigation etc. Rapid prototyping, also called as three
      dimensional (3D) printing, is a technology to create dimensionally accurate model
      from a computer-assisted design. Accurate physical models can be designed from
      the medical imaging data like CT scans and 3D printed to aid in various medical
      applications. Its application in orthopaedic field is on a rise, recently.
      However, there is no report on utilization of this technique in surgeries for
      FAI. We have reported a case of Cam type FAI in an eighteen year old boy, which
      we treated surgically by performing osteochondroplasty using safe surgical
      dislocation. We did CT based virtual surgical planning to design femoral head and
      neck jigs, which were 3D printed and used intra-operatively to guide for adequate
      and optimum excision of bone at head neck junction. We found these customized
      jigs accurate and useful for the surgery. However, a comparison study with
      various other techniques is warranted for a detailed research on its usefulness
      and challenges. The main purpose of this article is to elaborate on the technical
      steps for designing of jigs for 3D printing to guide in osteochondroplasty
      surgery for FAI.

PMID- 30202158
TI  - Computed tomography based 3D printed patient specific blocks for total knee
      replacement.
AB  - Objectives: 3D printing is an emerging technology and its use in orthopaedics is
      being explored. We discuss the role of computed tomography based 3D printed
      patient specific jigs in total knee replacement. We also discuss the various
      advantages of 3D printed patient specific jigs and the future scope of their use
      in total knee replacement. Methods: A search of English literature was done and
      articles discussing the role of CT scan based 3D printed patient specific jigs in
      total knee replacement were included in the study. Results: The role of 3D
      printed jigs in total knee replacement have been found in the prediction of
      femoral valgus angle, component sizing and in retained hardware. They have shown
      promise with studies suggesting they might improve the overall mechanical
      alignment of the knee. There are studies which have also studied the combined
      role of patient specific instruments with navigation. Conclusion: 3D printed jigs
      hold promise in total knee replacement. Their use in total knee replacement in
      the presence of retained hardware is useful for the surgeon. They have also
      showed promise in improving prediction of component sizing and improving
      mechanical alignment of the knee. Further studies with longer follow up and
      larger sample size will help in establishing their role in total knee
      replacement.

PMID- 30202157
TI  - Meniscal repair and regeneration: Current strategies and future perspectives.
AB  - The management of meniscal injuries remains difficult and challenging. Although
      several clinical options exist for the treatment of such injuries, complete
      regeneration of the damaged meniscus has proved difficult due to the limited
      healing capacity of the tissue. With the advancements in tissue engineering and
      cell-based technologies, new therapeutic options for patients with currently
      incurable meniscal lesions now potentially exist. This review will discuss basic
      anatomy, current repair techniques and treatment options for loss of meniscal
      integrity. Specifically, we focus on the possibility and feasibility of the
      latest tissue engineering approaches, including 3D printing technologies.
      Therefore, this discussion will facilitate a better understanding of the latest
      trends in meniscal repair and regeneration, and contribute to the future
      application of such clinical therapies for patients with meniscal injuries.

PMID- 30202159
TI  - 3D printing and its applications in orthopaedic trauma: A technological marvel.
AB  - Background: With rapid emergence of 3D printing technology, surgeons have
      recently started to apply this for nearly all areas of orthopaedic trauma
      surgery. Computed tomography or magnetic resonance images of trauma patients can
      be utilized for making graspable objects from 3D reconstructed images. Patient
      specific anatomical models can thereby be created. They enhance surgeon's
      knowledge of their patients' precise patho-anatomy, regarding both traumatized
      bones and soft tissue as well as normal areas, and therefore help in accurate
      preoperative planning. 3D printed patient specific instrumentation can help to
      achieve precise implant placement, and better surgical results. Most importantly,
      customized implants, casts, orthoses and prosthetics can be manufactured to match
      an individual's anatomy. Three dimensional (3D) printing, also called as
      'additive manufacturing' and 'rapid prototyping' is considered as the "second
      industrial revolution", and this appears to be especially true for orthopaedic
      trauma surgery. Methods: A literature search was performed for extracting all
      papers related to 3D Printing applications in orthopaedics and allied sciences on
      the Pubmed, and SCOPUS; using suitable key terms and Boolean operators ("3D
      Printing" OR "3 dimensional printing" OR "3D printed" OR "additive manufacturing"
      OR "rapid prototyping") AND (''Orthopaedics" OR "Orthopaedics'') AND ("Trauma" OR
      "Injury")in June 2018. Search was also performed in Web of Science, Cochrane
      Central Register of Controlled Trials and Cochrane Database of Systematic
      Reviews. No limits were set on the time period or evidence level, as 3D printing
      in orthopaedics is relatively recent and mainly low level evidence is available.
      Titles and abstracts were screened and all duplicate and unrelated papers were
      excluded. Papers related to orthopaedic trauma were manually selected for this
      review. Results: The search on Pubmed retrieved 144 Papers and similar search on
      SCOPUS retrieved 94 papers. Additional searches did not reveal more relevant
      papers. After excluding duplicates and unrelated papers, and on screening of
      titles and abstracts, 59 papers were considered for review. Papers related to
      spine fractures only were not included, as they have been covered in another
      paper in this journal issue. Conclusion: All over the world, orthopaedic
      Surgeon's and allied professionals and scientists are enthusiastically using 3D
      printing technology for designing patient specific models, instrumentation,
      implants, orthosis and prosthesis, besides 3D bioprinting of bone and cartilage
      scaffolding, and the same has been applied for nearly all areas of orthopaedic
      trauma surgery, from head to foot.

PMID- 30202161
TI  - 4D printing and its applications in Orthopaedics.

PMID- 30202162
TI  - Dental education in Saudi Arabia: Areas of attention.

PMID- 30202160
TI  - The evolution of three-dimensional technology in musculoskeletal oncology.
AB  - Musculoskeletal tumours pose considerable challenges for the orthopaedic surgeon
      during pre-operative planning, resection and reconstruction. Improvements in
      imaging technology have improved the diagnostic process of these tumours. Despite
      this, studies have highlighted the difficulties in achieving consistent resection
      free margins especially in tumours of the pelvis and spine when using
      conventional methods. Three-dimensional technology - three-dimensional printing
      and navigation technology - while relatively new, may have the potential to prove
      useful in the musculoskeletal tumour surgeon's arsenal. Three-dimensional
      printing (3DP) allows the production of objects by adding material layer by layer
      rather than subtraction from raw materials as performed conventionally. High
      resolution imaging, computer tomography (CT) and magnetic resonance imaging
      (MRI), are used to print highly complex and accurate items. Powder-based
      printing, vat polymerization-based printing and droplet-based printing are the
      common 3DP technologies applied. 3DP has been utilized pre-operatively in
      surgical planning and intra-operatively for patient specific instruments and
      custom made prosthesis. Pre-operative 3DP models transfer information to the
      surgeon in a concise yet exhaustive manner. Patient specific instruments are
      customized 3DP instruments utilized with the intention to easily replicate
      surgical plans. Complex musculoskeletal tumours pose reconstructive challenges
      and standard implants are often unable to reconstruct defects satisfactorily. The
      ability to use custom materials and tailor the pore size, elastic modulus and
      porosity of the 3DP prosthesis to be comparable to the patient's bone allows for
      a potential patient-specific prosthesis with unique incorporation and longevity
      properties. Similarly, navigation technology utilizes CT or MRI images to
      provides surgeons with real time intraoperative three-dimensional calibration of
      instruments. It has been shown to potentially allow surgeons to perform more
      accurate resections. These technological advancements have the potential to
      greatly impact the management of musculoskeletal tumours. 3D planning models,
      patient-specific instruments and customized 3DP implants and navigation should
      not be thought of as separate, but rather, patient-specific adaptation of
      relevant modes of application should be selected on a case-by-case basis when
      taking all unique factors of each case into consideration.

PMID- 30202163
TI  - The use of Bioceramics as root-end filling materials in periradicular surgery: A
      literature review.
AB  - Introduction: Periradicular surgery involves the placement of a root-end filling
      following root-end resection, to provide an apical seal to the root canal system.
      Historically several materials have been used in order to achieve this seal.
      Recently a class of materials known as Bioceramics have been adopted. The aim of
      this article is to provide a review of the outcomes of periradicular surgery when
      Bioceramic root-end filling materials are used on human permanent teeth in
      comparison to "traditional" materials. Methods & results: An electronic
      literature search was performed in the databases of Web of Science, PubMed and
      Google Scholar, between 2006 and 2017, to collect clinical studies where
      Bioceramic materials were utilised as retrograde filling materials, and to
      compare such materials with traditional materials. In this search, 1 systematic
      review and 14 clinical studies were identified. Of these, 8 reported the success
      rates of retrograde Bioceramics, and 6 compared treatment outcomes of mineral
      trioxide aggregate (MTA) and traditional cements when used as root-end filling
      materials. Conclusion: Bioceramic root-end filling materials are shown to have
      success rates of 86.4-95.6% (over 1-5 years). Bioceramics has significantly
      higher success rates than amalgam, but they were statistically similar to
      intermediate restorative material (IRM) and Super ethoxybenzoic acid (Super EBA)
      when used as retrograde filling materials in apical surgery. However, it seems
      that the high success rates were not solely attributable to the type of the root
      end filling materials. The surgical/microsurgical techniques and tooth prognostic
      factors may significantly affect treatment outcome.

PMID- 30202164
TI  - A systematic review on antibacterial activity of zinc against Streptococcus
      mutans.
AB  - Objectives: The aim of this study was to systematically review the growth
      inhibition effectiveness of zinc against Streptococcus mutans. The main question
      was, "Does the zinc inhibit the growth of oral Streptococcus mutans in vitro?
      Methods: Literature search on PubMed, Medline, and science direct databases was
      carried out for in vitro studies published in English from 1990 to 2016, and the
      reported outcomes of minimum inhibitory concentration (MIC), minimum bactericidal
      concentrations (MBC), zone of inhibition (ZOI) and bacterial count method using
      colony forming unit (CFU) were used to assess the antibacterial effectiveness of
      zinc. Results: Seventeen studies were included in this review. Seven studies
      reported MIC and MBC. Four studies reported ZOI, and eight studies reported CFU.
      MIC values using zinc chloride and zinc oxide nanoparticles were ranged from
      0.025 to 0.2 mM and 0.390 to 500 +/- 306.18 ug/ml respectively. MBC values using
      zinc oxide nanoparticles have ranged from 3.125 to 500 ug/ml. ZOI ranged from no
      inhibition zone to 21 +/- 1.4 mm using 23.1% zinc oxide. A considerable reduction
      in the bacterial count was reported after adding zinc. However, only two studies
      have reported no inhibitory effect of zinc. Conclusion: This review indicated a
      significant growth inhibition effectiveness of zinc even at lower concentrations
      which indicate it's safely to be used in oral health products.

PMID- 30202165
TI  - MIP-1alpha and MCP-1 as salivary biomarkers in periodontal disease.
AB  - Aim: Chemokines released by different host cells when exposed to the components
      of periodontopathic bacteria induce and maintain an inflammatory response in the
      periodontium. The aim of the study was to estimate the salivary levels of two
      chemokines, macrophage inflammatory protein-1 alpha (MIP-1alpha) and monocyte
      chemo attractant protein-1 (MCP-1) in health, gingivitis and periodontitis and to
      evaluate their role as reliable salivary biomarkers in discriminating gingivitis
      and periodontitis from health. Methods: A cross sectional study was designed to
      estimate the levels of MIP-1alpha and MCP-1 in whole unstimulated saliva from 75
      patients who were divided into healthy (Group 1, n = 25), gingivitis (Group 2, n
      = 25) and chronic generalized periodontitis (Group 3, n = 25). MIP-1alpha and MCP
      1 levels were estimated by using ELISA and were correlated with clinical
      parameters. ROC curve analysis was done to determine the sensitivity and
      specificity of these biomarkers in distinguishing periodontal disease from
      health. Results: Both the biomarkers were detected in all the saliva samples.
      There was a statistically significant difference in the concentration of both the
      analytes in Group 3 and Group 2 compared with Group 1 (p < 0.001). ROC curve
      analysis showed 100% sensitivity and specificity for MIP-1alpha and MCP-1 in
      discriminating periodontitis from health. For discriminating gingivitis from
      health, MIP-1alpha had a higher sensitivity and specificity (100% & 88%
      respectively) compared to MCP-1(84.1% & 80% respectively). Conclusion: There is a
      substantial increase in the concentration of both MIP-1alpha and MCP-1 with
      increasing severity of periodontal disease. Both the analytes showed promising
      results as biomarkers for discriminating periodontal disease from health.

PMID- 30202166
TI  - The current considerations in the fabrication of implant prostheses and the state
      of prosthetic complications: A survey among the dental technicians.
AB  - Purpose: To investigate the current considerations in the fabrication of dental
      implant prostheses (DIP) and the state of prosthetic complications from the
      dental technicians (DT) perspective. Methods: A self-designed pretested
      questionnaire and an informed consent were distributed to 150 certified DT
      working in dental laboratories of Riyadh, KSA. The demographic data, questions
      related to the implant fixed/removable prostheses and questions on the prosthetic
      complications related to the DIP were collected. Descriptive statistics and Chi
      square test were used for statistical analysis, considering a P-value of <0.05
      using SPSS. Results: 130 responses (response rate 83.6%) were received. 53% (n =
      69) of the DT received job orders for DIP from >20 dentists. 49% (n = 64) of
      dentists took the leading role in the treatment planning/designing. 48% (n = 62)
      and 52% (n = 68) of requests were for Cement and Screw retained DIP respectively.
      Custom abutments 37% (n = 49) choice of abutments. Porcelain fused to metal (PFM)
      34% (n = 44) and PFM with metal occlusal surface 55% (n = 71) were material of
      choice. 49% (n = 64) designing of implant overdentures were according to the
      dentist's instructions with Ball and Socket 48% (n = 63) to be the most common
      attachment. DT regarded poor implant location/orientation 38% (n = 49) and
      inaccuracies in impression/bite-registration 40% (n = 52) as the obstacles to
      success. Half 50% (n = 65) of the repairs were for facing damage/chipping of
      ceramic. Fracture of the denture base/tooth detachment 50% (n = 65) was common
      with implant over dentures. Conclusions: DT played a role and took decisions
      regarding the DIP. Frequent problems found by DT were poor implant location,
      discrepancies in impression/bite-registration, facing damage/chipping and
      damage/fracture of the denture base/prosthetic teeth. The frequency of these
      complications can be minimized by an increase in the prosthetic knowledge of the
      dentists and establishing clear protocols for communication between the dentist
      and the DT.

PMID- 30202167
TI  - Pregnancy-induced periodontal inflammation: Influence of salivary cytokines and
      antimicrobial proteins.
AB  - The aim of this study was to evaluate the association between pregnancy-induced
      periodontal inflammation and levels of some salivary cytokines and antimicrobial
      proteins (AMPs). The study was a cohort longitudinal study that included pregnant
      women attending a secondary health facility. Consented participants had oral
      examination and saliva sampling during pregnancy and post-partum (three months
      after pregnancy). Saliva samples were used for the analysis of cytokines (TNF
      alpha, IFN-gamma and IL-1beta) and AMPs (Lactoferin, Lysozyme, and beta defensin
      1) using ELISA. Data are presented as median with interquartile range and
      compared using related sample Wilcoxon signed rank test. Correlations between
      levels of the salivary factors and indices of periodontal inflammation were
      determined using Spearman's correlation test. Salivary flow rate, pH, levels of
      salivary IL-1beta and IFN-gamma were significantly lower; while gingival index,
      periodontal index and level of salivary TNF-alpha were significantly higher
      during pregnancy compared with postpartum period. However, salivary lactoferin,
      lysozyme and beta defensin-1 did not show significant difference comparing during
      pregnancy and postpartum period. Level of salivary IFN-gamma showed negative
      correlation with gingival index while level of salivary TNF-alpha showed positive
      correlation with gingival and periodontal indices. Lower levels of salivary IL
      1beta and IFN-gamma along with higher TNF-alpha concentration during pregnancy
      suggest their contributions to the pathophysiology of pregnancy-induced
      periodontal inflammation.

PMID- 30202168
TI  - In vitro study on the activity of essential oil and methanolic extract from
      Algerian Nigella sativa L. Seeds on the growth kinetics of micro-organisms
      isolated from the buccal cavities of periodontal patients.
AB  - An in vitro evaluation of the antimicrobial activity of essential oil (EO) and
      methanol extract (ME) from Algerian Nigella sativa L. seeds against microbial
      strains isolated from the oral cavities of periodontal patients was performed.
      Twelve Gram-positive bacteria, eleven Gram-negative bacteria and three
      microscopic fungi strains were isolated and identified. The antimicrobial
      activities of EO and ME were tested against Staphylococcus aureus, Staphylococcus
      epidermidis, Streptococcus pneumoniae, Enterococcus faecalis, Klebsiella
      pneumoniae, Proteus sp., Acinetobacter baumannii/calcoaceticus, Porphyromonas
      sp., Veillonella sp., Candida sp. and Saccharomyces sp.. The total polyphenol and
      flavonoids contents of ME were higher than those of EO. Thin layer chromatography
      showed that catechin, gallic acid and quercetin were most likely present in the
      extracts. Fourier transform infrared spectrometry analysis (FT-IR) indicated the
      presence of bands from the CO groups of acids, alcohols, phenols, and ethers and
      the C[bond, double bond]O band of aldehydes. Analysis of the antimicrobial
      activity of N. sativa extracts obtained by the microdilution method showed
      excellent bactericidal activity of the essential oil and moderate efficiency of
      the ME against all the microbes tested. Staphylococcus epidermidis and
      Porphyromonas sp. were the most sensitive to EO (minimum bactericidal
      concentration (MBC): 16,500 MUg/ml) at 48 h of incubation and, 125,000 MUg/ml of
      ME was the most active against all the microbes tested. However, after18 or 24 h,
      this efficiency was decreased in some strains. In addition, Saccharomyces sp. and
      Candida albicans were more sensitive to EO than ME during the incubation, while
      this efficiency was clearly not visible with the agar well method, and most
      microbes tested presented remarkable resistance to these extracts.

PMID- 30202170
TI  - Evaluation of some mechanical properties of a new silicone elastomer for
      maxillofacial prostheses after addition of intrinsic pigments.
AB  - Objective: The approximate life span of a silicone maxillofacial prosthesis is as
      short as 1.5-2 years of clinical service, then a new prosthesis should be
      fabricated. The most common reason for re-making the prosthesis is silicone
      mechanical properties degradation. The aim of this study was to assess some
      mechanical properties of VST-30 silicone for maxillofacial prostheses after
      addition of intrinsic pigments. Methods: Two types of intrinsic pigments (rayon
      flocking and burnt sienna); each of them was incorporated into silicone. One
      hundred and twenty samples were prepared and split into 4 groups according to the
      conducted tests (tear strength, hardness, surface roughness, and tensile strength
      and elongation percentage) with 30 samples for each test. Each group was equally
      split into three subgroups. Group (A) was without pigment (control group), group
      (B) was with rayon flocking and group (C) was with burnt sienna. Results: Samples
      with rayon flocking showed a highly significant decrease in hardness and there
      was a significant increase in tear strength, while there were non-significant
      differences in surface roughness, tensile strength and elongation percentage.
      Samples with burnt sienna showed a highly significant increase in tear strength
      and a highly significant decrease in hardness, but surface roughness, tensile
      strength and elongation percentage showed non-significant differences. However,
      there were non-significant differences between experimental groups in all tests.
      Conclusions: The addition of each of rayon flocking and burnt sienna changed the
      mechanical properties of the VST-30 silicone, while no superior pigment-silicone
      combination was revealed in all the conducted tests.

PMID- 30202169
TI  - Proximal contact areas of maxillary anterior teeth and their influence on
      interdental papilla.
AB  - Objectives: Open gingival embrasures leading to appearance of black triangles
      which apart from being unesthetic contribute towards food retention, adversely
      affecting the health of the periodontium. Correction of such papillary
      deformities is extremely challenging, which requires an in depth knowledge about
      the interproximal geometry for the appropriate management of interdental papilla.
      So, the present study was aimed to determine the proximal contact areas of
      maxillary anterior teeth and their influence on the interdental papilla.
      Materials and methods: In 200 periodontally healthy patients equally divided into
      21-40 years (Group I) and 41-60 years (Group II) of age group amounting to a
      total of 1400 interdental papillae in maxillary anterior teeth were examined to
      compute the apicocoronal Proximal contact area (PCA), Proximal contact area
      proportion (PCAP), and dimensions between alveolar crest and apical contact point
      (D1) to assess their influence on presence or absence of interdental papilla.
      Results: The PCA dimensions were maximum for Central incisor-Central incisor
      measuring about 3.90 +/- 0.93 mm and 3.97 +/- 0.90 mm for Group I males and
      females respectively and 3.86 +/- 1.22 mm and 3.63 +/- 1.14 mm for males and
      female patients in Group II respectively. There was a gradual reduction till
      Canine-Premolar. Similar trend was followed in PCAP and D1. Consistently more
      dimensions of D1 were observed in Group II as compared to Group I which
      influenced the presence of papilla which was predominantly found in Group I
      patients amongst both the sexes. Conclusion: There was a gradual decrease in the
      PCA and PCAP in the distal direction anteroposteriorly from maxillary central
      incisors to first premolars on either sides. The younger age group of both the
      sexes exhibit greater presence of interdental papilla owing to the lesser D1
      dimensions as compared to the older patients.

PMID- 30202171
TI  - Assessment of predictors of treatment outcome among patients with bacterial
      odontogenic infection.

PMID- 30202172
TI  - Facial profile based evaluation of gingival zenith position in maxillary central
      incisors among Saudi, Indian & Bangladeshi population.
AB  - Background: Recently quantitative evaluation of gingival zenith position was
      evaluated in different facial forms suggesting clinicians may need to evaluate
      patients facial form and then decide to distalise the Gingival Zenith position in
      relation to Vertical Bisected Midline (VBM). The aim of the study was to
      quantitatively evaluate the gingival zenith width in convex, concave and straight
      facial profiles for Saudi, Indian and Bangladeshi nationals. Materials/methods:
      114 subjects of each Saudi, Indian & Bangladeshi nationality were grouped into
      convex, concave and straight profile based on angle of convexity. Gingival zenith
      position (GZP) on #11 and #21 was evaluated on the scanned dental plaster model
      using CBCT. Inter and Intra group comparison was done using one-way ANOVA test.
      Results: Mean GZP values ranged from 0.84 mm to 1.10 mm, 0.75 mm to 1.02 mm and
      0.87 mm to 1.14 mm for Saudi, Indian and Bangladeshi subjects respectively.
      Statistically significant (p < 0.05) difference was observed in convex, concave
      and straight profile subjects of these nationalities. Conclusion: GZP variation
      does exist in different facial profiles of Saudi, Indian & Bangladeshi
      nationalities with respect to central incisors. Clinical significance: These
      findings help clinician to consider facial profile as important entity in
      designing the smile following restorative and prosthetic procedures such as crown
      lengthening, teeth selection, implant esthetics and laminates.

PMID- 30202173
TI  - Assessment of clinical efficacy of locally delivered 0.2% Thymoquinone gel in the
      treatment of periodontitis.
AB  - Objectives: To evaluate the potential benefits of local application of
      Thymoquinone gel as an adjunctive to scaling and root planing (SRP) in subjects
      with chronic periodontitis. Material and methods: Twenty subjects with 40 test
      sites were selected according to inclusion and exclusion criteria. They were
      further divided into 2 groups. Group I comprised of study subjects (Thymoquinone
      in addition to SRP) and Group II comprised of control subjects (only SRP).
      Clinical parameters such as Plaque Index (PI), Gingival Index (GI), Probing
      Pocket Depth (PPD), Relative Attachment Level (RAL), were monitored at baseline
      and 6 weeks post operatively. Alkaline phosphatase (ALP) levels in gingival
      crevicular fluid (GCF) were evaluated at baseline and 6 weeks post operatively
      using microcapillaries. In addition antimicrobial efficacy of Thymoquinone was
      evaluated against 3 bacteria using antimicrobial strains. Results: Statistically
      highly significant reduction was observed in PI, GI and PPD, rise in RAL and GCF
      ALP level in both the groups at 6 weeks from baseline. On comparison between
      Group I and Group II, former demonstrated statistically significant reduction in
      PPD, GCF-ALP levels and rise in RAL but statistically no significant differences
      were observed in PI and GI at 6 weeks. On microbiological assessment of 0.2%
      Thymoquinone gel, it was observed to be sensitive against P. gingivalis, A.
      actinomycetemcomitans and P. intermedia. Conclusion: Significant changes in
      clinical and biochemical parameters were achieved in the current study. Hence, it
      is concluded that intracrevicular application of 0.2% Thymoquinone gel could be a
      beneficial adjunct to SRP in treating chronic periodontitis.

PMID- 30202174
TI  - Growth factor release and enhanced encapsulated periodontal stem cells viability
      by freeze-dried platelet concentrate loaded thermo-sensitive hydrogel for
      periodontal regeneration.
AB  - Periodontium regeneration is a highly challenging process as it requires the
      regeneration of three different tissues simultaneously. The aim of this study was
      to develop a composite material that can be easily applied and can sufficiently
      deliver essential growth factors and progenitor cells for periodontal tissue
      regeneration. Freeze-dried platelet concentrate (FDPC) was prepared and
      incorporated in a thermo-sensitive chitosan/beta-glycerol phosphate (beta-GP)
      hydrogel at concentrations of 5, 10, or 15 mg/ml. The viscosity of the hydrogels
      was investigated as the temperature rises from 25  degrees C to 37  degrees C and
      the release kinetics of transforming growth factor (TGF-beta1), platelet-derived
      growth factor (PDGF-BB) and insulin-like growth factor (IGF-1) were investigated
      at four time points (1 h, 1 day, 1 week, 2 weeks). Periodontal ligament stem
      cells (PDLSCs) were isolated from human third molars and encapsulated in the
      different hydrogel groups. Their viability was investigated after 7 days in
      culture in comparison to standard culture conditions and non FDPC-loaded
      hydrogel. Results showed that loading FDPC in the hydrogel lowered the initial
      viscosity in comparison to the unloaded control group and did not affect the sol
      gel transition in any group. All FDPC-loaded hydrogel groups exhibited sustained
      release of TGF-beta1 and PDGF-BB for two weeks with significant difference
      between the different concentrations. The loading of 10 and 15 mg/ml of FDPC in
      the hydrogel increased the PDLSCs viability significantly compared to the
      unloaded hydrogel and was comparable to the standard culture conditions.
      Accordingly, it may be concluded that loading FDPC in a chitosan/beta-GP hydrogel
      can offer enhanced injectability, a sustained release of growth factors and
      increased viability of encapsulated stem cells which can be beneficial in
      periodontium tissue regeneration.

PMID- 30202175
TI  - Efficacy of two mouth rinse sprays in inhibiting Streptococcus mutans growth on
      toothbrush bristles.
AB  - Objective: To compare the efficacy of two types of mouth rinse sprays (Periogard
      and Plax) in inhibiting the growth of Streptococcus mutans (S. mutans) on
      toothbrush bristles used by children. Methods: An experimental comparative study
      was performed. The sample included 60 children aged 6-8 years with high caries
      index. Children were divided randomly into 3 groups (20 each) according to
      materials applied on toothbrush. Each group was further subdivided into 2
      subgroups A and B (10 each) according to the laboratory standards for processing
      microbiological specimens. Each toothbrush was placed in phosphate buffered
      saline, vortexed then serially diluted. Mitis salivarius bacitracin (MSB) agar
      plates were inoculated and incubated for 48 h. S. mutans colonies were identified
      by morphology, gram stain and biochemical tests. Results: Statistically,
      significant difference was observed between the three groups either when
      toothbrushes were processed immediately or when processed after 24 h. Group I
      showed highest bacterial count followed by group III whereas group II showed
      least bacterial count. Bacterial counts were significantly decreased by time in
      group I and group III while in group II no significant decrease as both subgroups
      showed very low bacterial count. Conclusions: Although both mouth rinses were
      effective against S. mutans toothbrush contamination, chlorhexidine gluconate
      proved to be better.

PMID- 30202176
TI  - Diagnostic challenges of an unusually large schwannoma of the mandible: Report of
      a case.
AB  - Schwannomas are slow-growing, benign neoplasms arising from the Schwann cells and
      are commonly reported as peripheral tumors in the head and neck region. Central
      intramandibular schwannomas are extremely rare lesions. We report a case of
      intramandibular schwannoma in a 70 year old male patient. Panoramic radiography
      revealed a large, multilocular radiolucent lesion with distinct borders involving
      the right mandibular body and ramus. A complete excision was achieved by removing
      the tumor followed by reconstruction of the mandible. The clinical, radiological,
      and histopathological features are discussed within the context of this case.

PMID- 30202177
TI  - Skeletal Class III correction in permanent dentition using reverse twin block
      appliance and fixed mechanotherapy.
AB  - The orthodontic management of patients with Class III malocclusion poses numerous
      prognostic and treatment challenges to the clinician. Various removable,
      orthopaedic, myofunctional and fixed appliances have been recommended for the
      correction of Class III malocclusion. The Reverse Twin Block (RTB) is a simple
      and well tolerated appliance which has often been used for the early management
      of such cases in mixed dentition. Cases reporting use of RTB in permanent
      dentition are however, limited. This article presents an insight into the
      encouraging results of reverse twin block (RTB) appliance used in conjunction
      with fixed mechanotherapy for the successful treatment of a 12-year-old patient
      presenting with skeletal Class III malocclusion and a concave facial profile. The
      RTB appliance helped establish a favourable environment for unrestricted
      maxillary growth, at the same time redirecting the mandibular growth to a
      clockwise direction and correcting the incisal relationship. The favourable
      treatment outcome and long-term stability achieved substantiates the feasibility
      of RTB appliance in mild to moderate skeletal Class III malocclusions in
      permanent dentition cases.

PMID- 30202178
TI  - Editorial: Advances in Community Partnered Participatory Research.

PMID- 30202179
TI  - Editorial: Developments in Community Partnered Participatory Research for
      Behavioral Health.

PMID- 30202180
TI  - Commentary: 25 Years of Community Partnered Participatory Research.

PMID- 30202181
TI  - The Community and Patient Partnered Research Network (CPPRN): Application of
      Patient-Centered Outcomes Research to Promote Behavioral Health Equity.
AB  - Objective: We describe the rationale, development, and progress on the Community
      and Patient Partnered Research Network (CPPRN). The CPPRN builds on more than a
      decade of partnered work and is designed to promote health equity by developing
      partnered research on behavioral health and social risk factors in Los Angeles
      and New Orleans. Setting: A community-academic partnership across Los Angeles
      County and New Orleans. Methods: Review of rationale, history, structure,
      activities and progress in applying community partnered participatory research
      (CPPR) to CPPRN. Findings: Patient and community stakeholders participated in all
      phases of development, including local and national activities. Key developments
      include partnered planning efforts, progress on aggregating a large, de
      identified dataset across county agencies, and development of an information
      technology-supported screening approach for behavioral and social determinants in
      health care, social, and community-based settings. Conclusion: The CPPRN
      represents a promising approach for research data networks, balancing the
      potential benefit of information technology and data analytic approaches while
      addressing potential risks and priorities of relevant stakeholders.

PMID- 30202182
TI  - Lessons on Patient and Stakeholder Engagement Strategies for Pipeline to Proposal
      Awards.
AB  - The Patient Centered Outcomes Research Institute (PCORI) supports patient
      centered clinical comparative effectiveness research (CER) including health
      disparities and engagement portfolios. In 2013, PCORI launched the Pipeline to
      Proposal (P2P) mechanism to support development of novel patient- and stakeholder
      centered partnerships focused on designing clinical CER funding proposals. By
      providing a tiered structure of successive small contracts and technical
      assistance, the P2P mechanism encourages development of new research partnerships
      among diverse stakeholders. As a comparatively new field, patient-centered
      outcomes research (PCOR) has few well-delineated methods for engaging patients
      and other non-scientists in effective teams with academics or clinicians to
      develop and implement rigorous, scientific research proposals. Community
      partnered participatory research (CPPR) provides a useful framework for
      structuring new partnerships. In this article we highlight the origins,
      development, and prospects of three current examples of funded P2P initiatives
      based in New Orleans and Los Angeles. We outline how these projects - Prisoner to
      Patient, the NOLA Partnership, and Resilience Among African American Men - use
      CPPR principles. We also describe how they have collaborated with, and
      contributed to, a two-way learning and knowledge exchange among members of the
      PCORI-funded Community and Patient Partnered Research Network. Lessons learned
      may be applicable to other groups planning to create new partnerships focused on
      implementing PCOR.

PMID- 30202183
TI  - Commentary: Community Partner Experiences in CPPR: What Participation in
      Partnered Research Can Mean to Community and Patient Stakeholders.
AB  - Community partners and stakeholders currently engaged in community partnered
      participatory research (CPPR) can provide personal and professional insight into
      the processes and outcomes surrounding the CPPR model. This insight may indicate
      alternative solutions or methods of care delivery that can improve the model and
      existing interventions. We conducted in-person and phone interviews with five
      community partners who are currently involved in CPPR. The interviews were audio-
      and video-recorded, transcribed, and major themes identified. Interviewees
      recounted their experiences with CPPR and reported various levels of personal
      (ie, behavioral) and professional growth as a result of their involvement.
      Interviewees also indicated that CPPR can highlight various aspects of existing
      interventions (eg, leadership structure, stakeholder representation, methods of
      provider-to-patient communication, and provision of resources) that may benefit
      from re-evaluation. Engagement in CPPR may offer various personal and
      professional benefits for individuals (ie, community partners) involved in stages
      of development, implementation, and dissemination. The benefits affect these
      individuals in several ways, from personal growth (eg, emotional maturity,
      behavioral progress, increased familial resiliency) to professional growth (eg,
      progression of one's career/role/responsibilities, organizational growth, learned
      skills). These maturations have secondary effects (eg, increased community
      resilience, strengthened relationships, community-based mentorships) impacting
      the communities in which these community partners serve.

PMID- 30202184
TI  - Creating Safe Spaces: A Community Health Worker-Academic Partnered Approach to
      Addressing Intimate Partner Violence.
AB  - Intimate partner violence (IPV) is a persistent public health problem in the
      United States, with an estimated one in three women experiencing rape, physical
      violence, and/or stalking by an intimate partner within her lifetime. Non
      Hispanic Black women disproportionately experience IPV, but there has been
      limited success in implementing culturally appropriate prevention programs and
      services for members of this population. Community health workers (CHWs) are
      trusted members of under-resourced communities who provide reliable health
      information and improve the cultural appropriateness of service delivery and may
      be a vital resource for developing new IPV interventions. Guided by the
      principles of community partnered participatory research, we developed the CHW
      led Safe Spaces project, which aimed to establish a strong academic-community
      partnership to focus on issues related to experiences of IPV and the prevention
      of IPV in New Orleans. In this article, we describe the development of our
      partnership including the formation of an advisory board, creation of a broad
      based stakeholder coalition, offering a community partnered participatory
      research training, conducting IPV education and outreach, and establishing a
      research agenda. Our processes are replicable and lessons learned may be relevant
      to other groups seeking to address IPV by leveraging the strengths of community
      academic collaborations and CHWs.

PMID- 30202185
TI  - Comparative Effectiveness of Coalitions Versus Technical Assistance for
      Depression Quality Improvement in Persons with Multiple Chronic Conditions.
AB  - Significance: Prior research suggests that Community Engagement and Planning
      (CEP) for coalition support compared with Resources for Services (RS) for program
      technical assistance to implement depression quality improvement programs
      improves 6- and 12-month client mental-health related quality of life (MHRQL);
      however, effects for clients with multiple chronic medical conditions (MCC) are
      unknown. Objective: To explore effectiveness of CEP vs RS in MCC and non-MCC
      subgroups. Design: Secondary analyses of a cluster-randomized trial. Setting: 93
      health care and community-based programs in two neighborhoods. Participants: Of
      4,440 clients screened, 1,322 depressed (Patient Health Questionnaire, PHQ8)
      provided contact information, 1,246 enrolled and 1,018 (548 with >=3 MCC)
      completed baseline, 6- or 12-month surveys. Intervention: CEP or RS for
      implementing depression quality improvement programs. Outcomes and Analyses:
      Primary: depression (PHQ9 <10), poor MHRQL (Short Form Health Survey, SF-12<40);
      Secondary: mental wellness, good physical health, behavioral health
      hospitalization, chronic homelessness risk, work/workloss days, services use at 6
      and 12 months. End-point regressions were used to estimate intervention effects
      on outcomes for subgroups with >=3 MCC, non-MCC, and intervention-by-MCC
      interactions (exploratory). Results: Among MCC clients at 6 months, CEP vs RS
      lowered likelihoods of depression and poor MHRQL; increased likelihood of mental
      wellness; reduced work-loss days among employed and likelihoods of >=4 behavioral
      health hospitalization nights and chronic homelessness risk, while increasing
      faith-based and park community center depression services; and at 12 months,
      likelihood of good physical health and park community center depression services
      use (each P<.05). There were no significant interactions or primary outcome
      effects for non-MCC. Conclusions: CEP was more effective than RS in improving 6
      month primary outcomes among depressed MCC clients, without significant
      interactions.

PMID- 30202186
TI  - Community Partners in Care: 6- and 12-month Outcomes of Community Engagement
      versus Technical Assistance to Implement Depression Collaborative Care among
      Depressed Older Adults.
AB  - Objective: Community Partners in Care, a community-partnered, cluster-randomized
      trial with depressed clients from 95 Los Angeles health and community programs,
      examined the added value of a community coalition approach (Community Engagement
      and Planning [CEP]) versus individual program technical assistance (Resources for
      Services [RS]) to implement depression collaborative care in underserved
      communities. This exploratory subanalysis examines 6- and 12-month outcomes among
      CPIC participants aged >50 years. Design: Community-partnered, cluster-randomized
      trial conducted between April 2010 and March 2012. Setting: Hollywood
      Metropolitan (HM) and South Los Angeles (SLA) Service Planning Areas (SPAs), Los
      Angeles, California. Participants: 394 participants aged >50 years with
      depressive symptoms (8-item Patient Health Questionnaire score >= 10).
      Intervention: A community-partnered multi-sector coalition approach (Community
      Engagement and Planning [CEP]) vs individual program technical assistance
      (Resources for Services [RS]) to implement depression collaborative care. Main
      Outcome Measures: Depressive symptoms (PHQ-8 score), mental health-related
      quality of life (MHRQL), community-prioritized outcomes including mental
      wellness, homelessness risk and physical activity, and services utilization.
      Results: At 6 months, CEP was more effective than RS at improving MHRQL and
      mental wellness among participants aged >50 years; no differences were found in
      the effects of CEP vs RS on other outcomes. No significant outcome differences
      between CEP and RS were found at 12 months. Conclusions: A multisector community
      coalition approach may offer additional benefits over individual program
      technical assistance to improve outcomes among depressed adults aged >50 years
      living in underserved communities.

PMID- 30202187
TI  - 12-Month Cost Outcomes of Community Engagement Versus Technical Assistance for
      Depression Quality Improvement: A Partnered, Cluster Randomized, Comparative
      Effectiveness Trial.
AB  - Objective: To compare community engagement and planning (CEP) for coalition
      support to implement depression quality improvement (QI) to resources for
      services (RS) effects on service-use costs over a 12-month period. Design:
      Matched health and community programs (N=93) were cluster-randomized within
      communities to CEP or RS. Setting: Two Los Angeles communities. Participants:
      Adults (N=1,013) with depressive symptoms (Patient Health Questionnaire (PHQ-8)
      >=10); 85% African American and Latino. Interventions: CEP and RS to support
      programs in depression QI. Main Outcome Measures: Intervention training and
      service-use costs over 12 months. Results: CEP planning and training costs were
      almost 3 times higher than RS, largely due to greater CEP provider training
      participation vs RS, with no significant differences in 12-month service-use
      costs. Conclusions: Compared with RS, CEP had higher planning and training costs
      with similar service-use costs.

PMID- 30202188
TI  - Maintaining Internal Validity in Community Partnered Participatory Research:
      Experience from the Community Partners in Care Study.
AB  - Objective: With internal validity being a central goal of designed experiments,
      we seek to elucidate how community partnered participatory research (CPPR)
      impacts the internal validity of public health comparative-effectiveness
      research. Methods: Community Partners in Care (CPIC), a study comparing a
      community-coalition intervention to direct technical assistance for disseminating
      depression care to vulnerable populations, is used to illustrate design choices
      developed with attention to core CPPR principles. The study-design process is
      reviewed retrospectively and evaluated based on the resulting covariate balance
      across intervention arms and on broader peer-review assessments. Contributions of
      the CPIC Council and the study's design committee are highlighted. Results: CPPR
      principles contributed to building consensus around the use of randomization,
      creating a sampling frame, specifying geographic boundaries delimiting the scope
      of the investigation, grouping similar programs into pairs or other small blocks
      of units, collaboratively choosing random-number-generator seeds to determine
      randomized intervention assignments, and addressing logistical constraints in
      field operations. Study protocols yielded samples that were well-balanced on
      background characteristics across intervention arms. CPIC has been recognized for
      scientific merit, has drawn attention from policymakers, and has fueled ongoing
      research collaborations. Conclusions: Creative and collaborative fulfillment of
      CPPR principles reinforced the internal validity of CPIC, strengthening the
      study's scientific rigor by engaging complementary areas of knowledge and
      expertise among members of the investigative team.

PMID- 30202189
TI  - Growing a Community-Academic Partnership: Lessons Learned in Forming a
      Qualitative Interview Team for the Community Partners in Care Study.
AB  - By engaging, partnering, and building trust with community members, research on
      vulnerable populations may offer opportunities to improve population health in
      communities that suffer from health disparities. While the literature on
      participatory and partnered approaches offers techniques and strategies for
      forming community-academic partnerships, less information is available about how
      partnerships can grow and evolve over time. In this article, we describe the
      expansion of a long-standing partnership that uses principles of community
      partnered participatory research (CPPR), a variant of community-based
      participatory research (CBPR). We outline the preparation and executive phases of
      conducting qualitative interviewing with highly vulnerable study participants who
      have already been participants in a longitudinal survey. We describe the
      challenges and concerns at each phase of the research and summarize some lessons
      learned. To grow and evolve, the partnership must constantly be reaffirmed in the
      experiences of new members.

PMID- 30202190
TI  - Whole Person Care in Under-resourced Communities: Stakeholder Priorities at Long
      Term Follow-Up in Community Partners in Care.
AB  - Objective: Depressed individuals may require help from different agencies to
      address health and social needs, but how such coordination occurs in under
      resourced communities is poorly understood. This study sought to identify
      priorities of Latino and African American depressed clients, explore whether
      service providers understand client priorities, and describe how providers
      address them. Methods: Between October 2014 and February 2015, we interviewed 104
      clients stratified by depression history and 50 representatives of different
      programs in health and social community agencies who participated in Community
      Partners in Care, a cluster-randomized trial of coalition-building approaches to
      delivering depression quality improvement programs. Clients were queried about
      their most pressing needs; program representatives identified their clients'
      needs and explained how they addressed them. Results: Physical and mental health
      were clients' top priorities, followed by housing, caring for and building
      relationships with others, and employment. While persistently depressed clients
      prioritized mental health, those with improved depression prioritized
      relationships with others. Program representatives identified housing,
      employment, mental health, and improving relationships with others as clients'
      top priorities. Needs assessment, client-centered services, and linkages to other
      agencies were main strategies used to address client needs. Conclusion: Depressed
      clients have multiple health and social needs, and program representatives in
      under-resourced communities understand the complexity of clients' needs. Agencies
      rely on needs assessment and referrals to meet their clients' needs, which
      enhances the importance of agency partnership in "whole person" initiatives. Our
      results illustrate agency capacity to adopt integrated care models that will
      address clients' multiple needs through multi-sector collaboration and describe
      potential strategies to help reach the goal of whole person care.

PMID- 30202191
TI  - Commentary: Applying the Community Partners in Care Approach to the Opioid
      Crisis.
AB  - Background: Given national concern over rising mortality from opioid use
      disorders (OUD) and challenges to increasing OUD treatment access, a coalition
      approach may hold promise to improve access and outcomes for diverse populations.
      We present considerations of a community-partnered working group on adapting the
      Community Partners in Care (CPIC) study and coalition approach to OUD. Method:
      During January 2016 through January 2017, academic, provider, consumer and policy
      stakeholders reviewed options to adapt CPIC's Resources for Services (RS) for
      individual program technical assistance and Community Engagement and Planning
      (CEP) for coalition support to OUD treatments, integrating stakeholder input into
      design options with estimated sample sizes. Findings: The working group
      recommended Community Reinforcement and Family Treatment (CRAFT) as a stakeholder
      support intervention to facilitate uptake and adherence to Medications for
      Addiction Treatment (MAT). Recommended implementation interventions for MAT/CRAFT
      were expert technical assistance supplemented by organizational readiness, and
      CEP for coalition support with a Learning Collaborative. Power estimation
      suggests that to compare implementation intervention effects on abstinence would
      require a somewhat larger enrolled sample and 3-4 times the screening sample as
      CPIC, and for mortality, at least 5-10 times the enrolled sample as CPIC.
      Discussion: Stakeholders viewed the CPIC design and interventions as feasible and
      acceptable as community-wide approaches for addressing the opioid epidemic, but
      comparing impacts on mortality would require large, multi-site trials.

PMID- 30202192
TI  - Stakeholder Perspectives on the Social Determinants of Mental Health in Community
      Coalitions.
AB  - Objective: Although evidence supports the potential for community coalitions to
      positively address social determinants of mental health, little is known about
      the views of stakeholders involved in such efforts. This study sought to
      understand county leaders' perspectives about social determinants related to the
      Health Neighborhood Initiative (HNI), a new county effort to support community
      coalitions. Design: Descriptive, qualitative study, 2014. Setting: Community
      coalitions, located in a large urban city, across eight service planning areas,
      that serve under-resourced, ethnic minority populations. Procedures: We conducted
      key informant interviews with 49 health care and community leaders to understand
      their perspectives about the HNI. As part of a larger project, this study focused
      on leaders' views about social determinants of health related to the HNI. All
      interviews were audio-recorded and transcribed. An inductive approach to coding
      was used, with text segments grouped by social determinant categories. Results:
      County leaders described multiple social determinants of mental health that were
      relevant to the HNI community coalitions: housing and safety, community violence,
      and employment and education. Leaders discussed how social determinants were
      interconnected with each other and the need for efforts to address multiple
      social determinants simultaneously to effectively improve mental health.
      Conclusions: Community coalitions have an opportunity to address multiple social
      determinants of health to meet social and mental health needs of low-resourced
      communities. Future research should examine how community coalitions, like those
      in the HNI, can actively engage with community members to identify needs and then
      deliver evidence-based care.

PMID- 30202193
TI  - Community Partnering for Behavioral Health Equity: Public Agency and Community
      Leaders' Views of its Promise and Challenge.
AB  - Objective: To understand potential for multi-sector partnerships among community
      based organizations and publicly funded health systems to implement health
      improvement strategies that advance health equity. Design: Key stakeholder
      interviewing during HNI planning and early implementation to elicit perceptions
      of multi-sector partnerships and innovations required for partnerships to achieve
      system transformation and health equity. Setting: In 2014, the Los Angeles County
      (LAC) Board of Supervisors approved the Health Neighborhood Initiative (HNI) that
      aims to: 1) improve coordination of health services for behavioral health clients
      across safety-net providers within neighborhoods; and 2) address social
      determinants of health through community-driven, public agency sponsored
      partnerships with community-based organizations. Participants: Twenty-five semi
      structured interviews with 49 leaders from LAC health systems, community-based
      organizations; and payers. Results: Leaders perceived partnerships within and
      beyond health systems as transformative in their potential to: improve access,
      value, and efficiency; align priorities of safety-net systems and communities;
      and harness the power of communities to impact health. Leaders identified trust
      as critical to success in partnerships but named lack of time for relationship
      building, limitations in service capacity, and questions about sustainability as
      barriers to trust-building. Leaders described the need for procedural innovations
      within health systems that would support equitable partnerships including
      innovations that would increase transparency and normalize information exchange,
      share agenda-setting and decision-making power with partners, and
      institutionalize partnering through training and accountability. Conclusions:
      Leaders described improving procedural justice in public agencies' relationships
      with communities as key to effective partnering for health equity.

PMID- 30202194
TI  - A Window of Opportunity: Visions and Strategies for Behavioral Health Policy
      Innovation.
AB  - Objective: The New York City's Thrive (ThriveNYC) and the Los Angeles County
      Health Neighborhood Initiative (HNI) are two local policies focused on addressing
      the social determinants of behavioral health as a preventive strategy for
      improving health service delivery. On January 29, 2016, leaders from both
      initiatives came together with a range of federal agencies in health care, public
      health, and policy research at the RAND Corporation in Arlington, Virginia. The
      goal of this advisory meeting was to share lessons learned, consider research and
      evaluation strategies, and create a dialogue between stakeholders and federal
      funders - all with the purpose to build momentum for policy innovation in
      behavioral health equity. Methods: This article analyzes ethnographic notes taken
      during the meeting and in-depth interviews of 14 meeting participants through
      Kingdon's multiple streams theory of policy change. Results: Results demonstrated
      that stakeholders shared a vision for behavioral health policy innovation focused
      on community engagement and social determinants of health. In addition, Kingdon's
      model highlighted that the problem, policy and politics streams needed to form a
      window of opportunity for policy change were coupled, enabling the possibility
      for behavioral health policy innovation. Conclusions: The advisory meeting
      suggested that local policy makers, academics, and community members, together
      with federal agents, are working to implement behavioral health policy
      innovation.

PMID- 30202195
TI  - Applying a Trauma Informed School Systems Approach: Examples from School
      Community-Academic Partnerships.
AB  - Objectives: Schools can play an important role in addressing the effects of
      traumatic stress on students by providing prevention, early intervention, and
      intensive treatment for children exposed to trauma. This article aims to describe
      key domains for implementing trauma-informed practices in schools. Design: The
      Substance Abuse and Mental Health Administration (SAMHSA) has identified trauma
      informed domains and principles for use across systems of care. This article
      applies these domains to schools and presents a model for a Trauma-Informed
      School System that highlights broad macro level factors, school-wide components,
      and tiered supports. Community partners from one school district apply this
      framework through case vignettes. Results: Case 1 describes the macro level
      components of this framework and the leveraging of school policies and financing
      to sustain trauma-informed practices in a public health model. Case 2 illustrates
      a school founded on trauma-informed principles and practices, and its promotion
      of a safe school environment through restorative practices. Case 3 discusses the
      role of school leadership in engaging and empowering families, communities, and
      school staff to address neighborhood and school violence. Conclusions: This
      article concludes with recommendations for dissemination of trauma-informed
      practices across schools at all stages of readiness. We identify three main areas
      for facilitating the use of this framework: 1) assessment of school staff
      knowledge and awareness of trauma; 2) assessment of school and/or district's
      current implementation of trauma-informed principles and practices; 3)
      development and use of technology-assisted tools for broad dissemination of
      practices, data and evaluation, and workforce training of clinical and non
      clinical staff.

PMID- 30202196
TI  - A Cross-Site Partnership to Examine Implementation and Sustainability of a School
      Based Trauma Program.
AB  - Objectives: Schools have been identified as an ideal setting for increasing
      access to mental health services particularly for underserved minority youth. The
      emerging field of implementation science has begun to systematically investigate
      strategies for more efficiently integrating evidence-based practices into
      community settings. Significantly less translational research has focused
      specifically on the school setting. To address this need, we examined the
      implementation of a school-based trauma intervention across three distinct
      regions. Design: We conducted key informant interviews guided by Mendel's
      Framework of Dissemination in Health Services Intervention Research with multiple
      school stakeholders to examine what school organizational characteristics
      influence the adoption and implementation process and sustainability of Cognitive
      Behavioral Intervention for Trauma in Schools (CBITS). Participants were selected
      from schools in three geographic regions in the United States: Western,
      Midwestern, and Southern. Results: Our findings reveal that while sites had some
      common organizational factors that appeared to facilitate implementation, regions
      differed in how they compensated for less robust implementation domains. Across
      all regions, school stakeholders recognized the need for services to support
      students impacted by trauma. In the Western region, there was no centralized
      district policy for implementation; therefore, implementation was facilitated by
      school-level change agents and supervision support from the district mental
      health unit. In the Midwestern region, centralized district policies drove
      implementation. In both the Midwestern and Southern regions, implementation was
      facilitated by collaboration with a local mental health agency. Conclusions: This
      study contributes to the paucity of empirical information on the organizational
      factors that influence the implementation of evidence-based mental health
      interventions in schools. Our findings reveal that different implementation
      strategies across policies, structures, and resources can result in
      implementation of a school-based intervention. Frameworks such as Mendel's can be
      helpful in identifying areas of strength and improvement of implementation within
      a school organization.

PMID- 30202197
TI  - Voices from Minority Youth on Help-Seeking and Barriers to Mental Health
      Services: Partnering with School-Based Health Centers.
AB  - Objective: Schools and school-based health centers (SBHCs) play an important role
      in reducing disparities in access to mental health treatment. However, there is a
      need to increase student engagement in school mental health services. This study
      sought to understand the perceptions of low-income minority youth on help-seeking
      and barriers to mental health services at SBHC sites. Setting: A network of
      SBHCs, called Wellness Centers, developed as part of a strategic plan to serve
      students and community members in under-resourced areas of a large urban school
      district. Participants and Procedures: We conducted focus groups with 76 middle
      and high school students at nine SBHC sites through a community-academic
      partnered approach from January to May 2014. The focus groups were audio
      recorded, transcribed, and major themes coded with Atlas.ti.5.1. Results:
      Students identified teachers as a primary source of support for mental health
      issues, followed by peers and mental health counselors. Students felt that trust
      and connection were vital for help-seeking. Barriers to using SBHCs included:
      embarrassment; fear of judgment; concerns about confidentiality; a sense that
      they should keep things inside; and lack of awareness. Conclusions: Despite the
      resources available at SBHCs, students face barriers to help-seeking. SBHCs can
      help teachers and school staff gain awareness of mental health issues and
      services available to students. The students' recommendations-making SBHCs more
      comfortable, raising mental health awareness, and bolstering connections with
      school and SBHC staff-may improve engagement in mental health services at schools
      with SBHCs.

PMID- 30202198
TI  - Development and Evaluation of Two Integrated Care Models for Children Using a
      Partnered Formative Evaluation Approach.
AB  - Objective: To describe the development and evaluation of two integrated care
      models using a partnered formative evaluation approach across a private
      foundation, clinic leaders, providers and staff, and a university-based research
      center. Design: Retrospective cohort study using multiple data sources. Setting:
      Two federal qualified health care centers serving low-income children and
      families in Chicago. Participants: Private foundation, clinic and academic
      partners. Interventions: Development of two integrated care models and partnered
      evaluation design. Main Outcome Measures: Accomplishments and early lessons
      learned. Results: Together, the foundation-clinic-academic partners worked to
      include best practices in two integrated care models for children while
      developing the evaluation design. A shared data collection approach, which
      empowered the clinic partners to collect data using a web-based tool for a
      prospective longitudinal cohort study, was also created. Conclusion: Across three
      formative evaluation stages, the foundation, clinic, and academic partners
      continued to reach beyond their respective traditional roles of project
      oversight, clinical service, and research as adjustments were collectively made
      to accommodate barriers and unanticipated events. Together, an innovative shared
      data collection approach was developed that extends partnered research to include
      data collection being led by the clinic partners and supported by the technical
      resources of a university-based research center.

PMID- 30202199
TI  - Development of a Telehealth-Coordinated Intervention to Improve Access to
      Community-Based Mental Health.
AB  - Objective: To develop an intervention to improve the mental health referral and
      care process for children referred by primary care providers (PCPs) to community
      mental health clinics (MHCs) using a community partnered approach. Design: A
      Project Working Group (PWG) with representatives from each partner organization
      met monthly for 6 months. Setting: Multi-site federally qualified health center
      (FQHC) and two community MHCs in Los Angeles county. Participants: 26
      stakeholders (14 FQHC clinic providers/staff, 8 MHC providers/staff, 4 parents)
      comprised the PWG. Data Sources: Qualitative interviews, PWG meeting notes,
      intervention processes and workflow reports. Intervention: The PWG reviewed
      qualitative data from stakeholders (interviews of 7 parents and 13
      providers/staff). The PWG met monthly to identify key transition points where
      access to and coordination of care were likely compromised and to develop
      solutions. Results: Three critical transition points and system solutions were
      identified: 1) Parents refuse initial referral to the MHC due to stigma regarding
      mental health services. Solution: During initial referral, parents watch a video
      introducing them to the MHC. 2) Parents don't complete the MHC's screening after
      referral. Solution: A live videoconference session connecting parents at the FQHC
      with MHC staff ensures completion of the screening and eligibility process. 3)
      PCPs reject transfer of patients back to primary care for ongoing psychotropic
      medication management. Solution: Regularly scheduled live videoconferences
      connect PCPs and MHC providers. Conclusions: A community partnered approach to
      care design utilizing telehealth for care coordination between clinics can
      potentially be used to address key challenges in MHC access for children.

PMID- 30202200
TI  - Partnering with African American Churches to Create a Community Coalition for
      Mental Health.
AB  - Community partnered participatory research (CPPR) emphasizes community
      engagement, respect, and empowerment as guiding principles to promote mental
      health equity. This article describes the "Vision" stage of a CPPR-informed model
      to implement evidence-based practices for depression in two African American
      churches in Harlem, New York. Essential parts of the Vision include engagement of
      stakeholders and collaborative planning. The engagement process increased
      awareness about the project via a community-focused mental health symposium. The
      collaborative planning stage resulted in creating a multi-disciplinary Community
      Coalition for Mental Health, establishing the Coalition's values, agreeing to
      change the initial chosen study intervention from Interpersonal Counseling to
      Mental Health First Aid, and developing a website to disseminate the group's
      work. Key lessons learned from our partnered process are: 1) support from the
      lead pastor is crucial; 2) balancing community and academic interests can be
      challenging; 3) icebreaker activities foster relationships and reinforce CPPR
      principles; 4) multiple communication channels can enhance community
      participation; and, 5) should organize data in ways that make them easier to
      interpret.

PMID- 30202201
TI  - Engaging African American Veterans with Health Care Access Challenges in a
      Community Partnered Care Coordination Initiative: A Qualitative Needs Assessment.
AB  - Background: Little has been written about engaging potentially eligible members
      of a health care system who are not accessing the care to which they are
      entitled. Knowing more about the experiences of African American Veterans who
      regularly experience health care access challenges may be an important step
      toward equitable, coordinated Veterans Health Administration (VHA) care. This
      article explores the experiences of African American Veterans who are at risk of
      experiencing poor care coordination. Design: We partnered with a community
      organization to recruit and engage Veterans in three exploratory engagement
      workshops between October 2015 and February 2016. Participants and Setting:
      Veterans living in South Los Angeles, California. Main Outcome Measures: Veterans
      were asked to describe their experiences with community care and the VHA, a
      division of the US Department of Veterans Affairs (VA). Field notes taken during
      the workshops were analyzed by community and academic partners using grounded
      theory methodology to identify emergent themes. Results: 12 Veterans and 3 family
      members of Veterans participated in one or more engagement workshops. Their trust
      in the VA was generally low. Positive themes included: Veterans have knowledge to
      share and want to help other Veterans; and connecting to VA services can result
      in positive experiences. Negative themes included: functional barriers to
      accessing VA health care services; insensitive VA health care environment; lack
      of trust in the VA health care system; and Veteran status as disadvantageous for
      accessing non-VA community services. Conclusions: Veterans living in underserved
      areas who have had difficulty accessing VA care have unique perspectives on VA
      services. Partnering with trusted local community organizations to engage
      Veterans in their home communities is a promising strategy to inform efforts to
      improve care access and coordination for vulnerable Veterans.

PMID- 30202202
TI  - An Assets-Based Approach to Co-Producing a Culturally Adapted Family Intervention
      (CaFI) with African Caribbeans Diagnosed with Schizophrenia and Their Families.
AB  - Objective: To determine how to improve the cultural appropriateness and
      acceptability of an extant evidence-based model of family intervention (FI), a
      form of 'talking treatment,' for use with African Caribbean service users
      diagnosed with schizophrenia and their families. Design: Community partnered
      participatory research (CPPR) using four focus groups comprising 31 key
      stakeholders. Setting: Community locations and National Health Service (NHS)
      mental health care settings in northwest England, UK. Participants: African
      Caribbean service users (n=10), family members, caregivers and advocates (n=14)
      and health care professionals (n=7). Results: According to participants,
      components of the extant model of FI were valid but required additional items
      (such as racism and discrimination and different models of mental health and
      illness) to improve cultural appropriateness. Additionally, emphasis was placed
      on developing a new ethos of delivery, which participants called 'shared
      learning.' This approach explicitly acknowledges that power imbalances are likely
      to be magnified where delivery of interventions involves White therapists and
      Black clients. In this context, therapists' cultural competence was regarded as
      fundamental for successful therapeutic engagement and outcomes. Conclusions:
      Despite being labelled 'hard-to-reach' by mainstream mental health services and
      under-represented in research, our experience suggests that, given the
      opportunity, members of the African Caribbean community were highly motivated to
      engage in all aspects of research. Participating in research related to
      schizophrenia, a highly stigmatized condition, suggests CPPR approaches might
      prove fruitful in developing interventions to address other health conditions
      that disproportionately affect members of this community.

PMID- 30202203
TI  - Participatory Technology Development to Enhance Community Resilience.
AB  - Objective: To assess the feasibility of a novel, partnered technology development
      process to co-create mobile health applications (apps) addressing community
      health priorities, using psychoeducation of cognitive behavioral therapy (CBT)
      principles for enhancing resilience as an example. Design: Stakeholder
      engagement, workgroups, pilot feasibility study using mixed methods during
      October 2013 through January 2016 over three phases: 1) defining the vision of
      the project and increasing technical capacity, 2) co-development and pilot
      testing of the app, and 3) planning for sustainability. Setting: An academic
      community partnership in South Los Angeles, California. Participants: Eight
      stakeholders; 30 pilot participants from the community. Main Outcome Measures:
      Qualitative analysis of audio-recordings of the app development process and
      stakeholder interviews, surveys of stakeholders' perception of the development
      process, app use data, and feedback from pilot participants. Results: The
      participatory technology development process resulted in creation and pilot
      testing of a resiliency-focused text messaging app. Of the 1,107 messages sent,
      23 out of 30 (77%) app users responded to explore interactive content.
      Stakeholders reported increased perceived competency in creating mobile apps and
      that the process fostered a culture of co-leadership. There was also sustained
      engagement in mobile app development by stakeholders beyond the initial project
      period. Conclusions: This is the first study, to our knowledge, to demonstrate
      the feasibility of participatory technology development, an approach involving
      direct participation in the development, tailoring and maintenance of a mobile
      app by a broad set of stakeholders with high representation from racial/ethnic
      minorities from an under-resourced community. Participatory technology
      development is a promising approach for creating sustainable, relevant and
      engaging health technologies across different technological, clinical and
      community settings.

PMID- 30202205
TI  - Housing decisions among homeless families involved in the child welfare system.
AB  - The present study embedded a qualitative sub-study within a randomized controlled
      trial of housing services for child welfare-involved families to examine housing
      decisions made in the face of homelessness and child protection. Participants
      included a representative sample of caregivers (n = 19) randomized to receive the
      Family Unification Program - a permanent housing intervention for inadequately
      housed families under investigation for child abuse or neglect - or child welfare
      services-as-usual. Qualitative interviews 12 months after randomization assessed
      housing decision-making processes involved in keeping families safe and stable.
      Results indicated a push-pull dynamic that constrained housing choices regardless
      of whether permanent housing was made available. Caregiver housing decisions were
      constrained by time limitations, affordability, and access to services, while
      child and family safety was perceived as less important. Findings emphasize the
      need for housing informed child welfare services to ensure the long-term safety
      of children in families experiencing homelessness.

PMID- 30202204
TI  - Community Partnership in Precision Medicine: Themes from a Community Engagement
      Conference.
AB  - Background: Patient and community engagement in under-resourced communities is a
      key issue for precision medicine research. We report proceedings from a community
      academic partnered conference in Los Angeles to promote community understanding
      of precision medicine and generate engagement recommendations. Methods: Planning
      group review of planning, presentations, and audience discussions from
      facilitator notes and participant survey data from a one-day conference.
      Findings: Community-academic planning broadened community participation and
      presentations. More than 80% of survey participants indicated they would
      participate in the national precision medicine initiative, and most were willing
      to share diverse sources of data. Discussions identified trust concerns related
      to historical research abuses, data privacy, potential effects of findings on
      health care, personal safety, research procedures, the time-frame for benefit,
      and confusion about different initiatives. Concerns were balanced by belief in
      science to improve health. Recommendations included a community partnered
      participatory approach with support for local community and academic teams to
      engage stakeholders with written/online resources and partnered workgroups
      addressing key concerns. Conclusion: Conference participants expressed high
      willingness to participate in precision medicine studies, but discussions
      highlighted trust and transparency issues and suggested community partnered
      research with local capacity building.

PMID- 30202206
TI  - Expression Levels of Candidate Circulating microRNAs in Early-Onset Neonatal
      Sepsis Compared With Healthy Newborns.
AB  - The high mortality rate of neonatal sepsis is directly connected with time
      consuming diagnostic methods that have low sensitivity and specificity. The need
      of the hour is to develop novel diagnostic techniques that are rapid and more
      specific. In this study, we estimated the expression levels of circulating
      microRNAs (miRNAs) that are involved in regulating immune response genes and
      underlying inflammatory responses, which may be used for sepsis diagnosis. The
      total circulating miRNA was isolated and the candidate miRNAs (miR-132, miR-146a,
      miR-155, and miR-223) were quantified by real-time polymerase chain reaction
      technique. Statistical analysis revealed that miR-132 (P < .01) and miR-223 (P <
      .05) were downregulated in septic newborns compared with healthy babies. The
      decrease in expression of miR-132 and miR-223 may be associated with increased
      expression of immune-related genes involved in TLR (Toll-like receptor) signaling
      pathway. Further case-control studies with large sample size are required to
      identify the potential of miRNAs in neonatal sepsis diagnosis.

PMID- 30202207
TI  - Corrigendum.
AB  - [This corrects the article DOI: 10.4137/GEI.S32477.].

PMID- 30202208
TI  - The Pediatric Personal Care Allocation Model for Home Care (PCAM): A Personal
      Care Case-Mix Model for Children Facing Special Health Care Challenges.
AB  - Background: State Medicaid programs in the United States provide services to
      children with special health care challenges through the Early Prevention,
      Screening, Diagnostic, and Treatment program. One element of the services
      provided is Medicaid Personal Care Services (PCS), which are intended to correct
      or ameliorate any functional impairments faced by a child or youth (C/Y) in the
      community. Previous research indicates that considerable variation in the
      allocation of PCS depends on the assessor. A case-mix model is developed that
      might make the distribution of such services more uniform and equitable. Data:
      The sample in this research includes 2708 C/Y aged 4 to 20 who were receiving PCS
      in Texas in 2008. Results: A case-mix model was developed that groups sample
      members into 33 categories based on the number of hours of PCS authorized by an
      assessor. The Pediatric Personal Care Allocation Model (PCAM) explains 27% of the
      variance in the allocation of PCS hours. Discussion: The implementation of the
      PCAM should provide guidance to assist in ensuring that C/Y facing similar
      functional challenges receive similar levels of PCS. However, implementation of
      any case-mix model is only a first step in moving to a prospective payment system
      for PCS.

PMID- 30202209
TI  - Accounting for What Matters to Patients in the G-DRG System: A Stakeholder's
      Perspective on Integrating Functioning Information.
AB  - Functioning information constitutes a relevant component for determining
      patients' service needs and respective resource use. Diagnosis-Related Group
      (DRG) systems can be optimized by integrating functioning information. First
      steps toward accounting for functioning information in the German DRG (G-DRG)
      system have been made; yet, there is no systematic integration of functioning
      information. The G-DRG system is part of the health system; it is embedded in and
      as such dependent on various stakeholders and vested interests. This study
      explores the stakeholder's perspective on integrating functioning information in
      the G-DRG system. A qualitative interview study was conducted with national
      stakeholders in 4 groups of the G-DRG system (health policy, administration,
      development, and consultations). Interviews were analyzed using inductive
      thematic analysis. In total, 14 interviews were conducted (4 administration and
      10 consultation group). Three main themes were identified: (1) functioning
      information in the G-DRG system: opportunities and obstacles, (2) general aspects
      concerning optimizing G-DRG systems by integrating additional information, and
      (3) ideas and requirements on how to proceed. The study offers insights into the
      opportunities and obstacles of integrating functioning information in the G-DRG
      system. The relevance of functioning information was evident. However, the value
      of functioning information for the G-DRG system was seen critically. Integrating
      functioning information alone does not seem to be sufficient and a systems
      approach is needed.

PMID- 30202210
TI  - Relationships in Ongoing Structural Maintenances of the Two Cerebral Cortices of
      an Individual Brain.
AB  - A human brain has separate left and right cerebral cortices, each of which must
      be continuously structurally maintained during adulthood. There is no
      understanding of how ongoing structural maintenances of separate parts of a
      mature individual brain, including the 2 cortices, are related. To explore this
      issue, this study used an unconventional N-of-1 magnetic resonance imaging time
      series paradigm to identify relationships between maintenances of structural
      thicknesses of the 2 cortices in an adult human brain over week intervals for 6
      months. The results suggest that maintenances of left and right cortical
      thicknesses were symmetrically related in some, but asymmetrically related in
      other, respects. For matched times, thickness magnitudes and variations on the 2
      sides were positively correlated and appeared to reflect maintenance symmetry.
      Maintenance relationships also extended from earlier to later times with temporal
      continuity and apparent "if-then" contingencies which were reflected in symmetry
      and asymmetry dynamics spanning 1- to 2-week periods. The findings suggest
      concepts of individual brain cortical maintenance symmetry, asymmetry, and
      temporal continuity dynamics that have not been previously recognized. They have
      implications for defining cortical maintenance traits or states and for
      development of N-of-1 precision medicine paradigms that can contribute to
      understanding individual brain health.

PMID- 30202212
TI  - Skin-Related Complications Among Adolescents With Type 1 Diabetes Using Insulin
      Pump Therapy.
AB  - Background: To identify the skin-related complications in adolescents with type 1
      diabetes (T1D) using the insulin pump therapy (IPT). Methods: A total of 64 T1D
      adolescents (between ages 13 and 19) using the insulin pump were included in this
      cross-sectional study. They had visited the Diabetes Clinic at Diabetes Treatment
      Center, Prince Sultan Military Medical City, Saudi Arabia, for treatment from
      January 2018 to March 2018. Data on the prior and present skin-related
      complications, for a 6-month interval, were gathered via a closed/structured
      questionnaire. Besides this, demographic information was also recorded. Results:
      From the patients in this study (n = 64), 9.3% experienced 3 or more skin-related
      complications, whereas 7.8% patients registered 2 and 25% had only 1 such
      disorder. However, in 37 patients (51.8%), there was no evidence of skin-related
      complications. Significantly, the female revealed a higher level of issues (P =
      .036), >3 years on IPT (P = .039), negligence of infusion set rotation (P =
      .001), needle length of 9 mm (P = .021), and beyond 3 days for catheter
      replacement (P = .022). The factors age, body mass index, diabetes duration, and
      insulin dosage remained quite unaffected. From the regression analysis, the
      factors female gender, catheter replacement, and infusion set rotation showed up
      as the independent risk factors for the skin complications. Conclusions: The IPT
      users invariably experience dermatologic conditions. Through this study, female
      gender, length of IPT usage time, and infusion set rotations were identified as
      the independent risk factors responsible for the skin issues.

PMID- 30202211
TI  - Efficacy and Safety of Valsartan or Chlorthalidone vs. Combined Valsartan and
      Chlorthalidone in Patients With Mild to Moderate Hypertension: The VACLOR Study.
AB  - Objective: To evaluate the efficacy and safety of valsartan (V) or chlorthalidone
      (C) monotherapy in comparison with a fixed combination of valsartan and
      chlorthalidone (V + C). Methods: This 12-week multicenter randomized three-arm
      open-label study randomly allocated 72 patients to V or C as monotherapy or a
      combination of V + C. The aim was to measure changes in office systolic blood
      pressure (SBP) and diastolic blood pressure (DBP) and in 24-hour ambulatory blood
      pressure monitoring (ABPM) from baseline to week 12, in addition to medication
      tolerability. Results: The proportion of patients achieving target BP in office
      at week 12 was not statistically different for the three groups. However,
      comparisons of daytime and nighttime 24-hour ABPM values from baseline to week 12
      revealed significant differences in nighttime mean SBP for the three groups, due
      to a significantly greater reduction in the values in patients assigned to the V
      + C group (-14.7 vs. -8.7 vs. -10.7, P = .042, V+C; V; C, respectively). Although
      patients assigned to the V + C group also had greater nighttime reduction in mean
      DBP values compared with those in the other groups, this difference was not
      statistically significant. The incidence of adverse events did not differ
      significantly. Conclusion: In patients with hypertension treated with V, C, and
      both medications combined, the fixed combination of V + C provided a
      significantly greater reduction of late night to early morning BP values when
      interventions were assessed with 24-hour ABPM. Trial registration:
      clinicaltrials.gov Identifier: NCT.01850160,
      https://clinicaltrials.gov/ct2/show/NCT01850160.

PMID- 30202214
TI  - Patterns of antibiotic use and administration in hospitalized patients in Jordan.
AB  - Background: Inappropriate use of antibiotics is the leading cause of emergence of
      resistance. It has been estimated that two million people in the United States
      had infection with resistant bacteria, resulting in 23,000 deaths annually. In
      Jordan, more than 50% of physicians prescribe antibiotics for inappropriate
      indication such as common cold, and approximately 67% of adult Jordanians believe
      that antibiotics should be used for this purpose. It is essential to follow
      antibiotics prescription guidelines in order to maximize effectiveness and
      enhance patient safety. Objective: The study aim was to describe patterns of
      antibiotics prescription and adherence to guidelines of IV to oral antibiotic
      conversion in elderly patients visiting King Abdullah University Hospital (KAUH).
      Methods: A retrospective cross sectional study was conducted on hospitalized
      patients who were prescribed IV antibiotics. Sociodemographic and clinical data
      in addition to a list of IV prescribed antibiotics was collected by referring to
      information technology department at KAUH. Patients' eligibility for antibiotic
      conversion from IV to oral route was then evaluated based on Society for
      Healthcare Epidemiology of America criteria. Results: A total of 110 antibiotics
      were dispensed for 80 patients, imipenem/cilastatin was the most prescribed
      antibiotic (41.25%), followed by cephalosporines which were prescribed for 27.5%
      of the participants. Approximately half of the study patients (47.5%) were
      prescribed IV antibiotics despite their eligibility for oral conversion.
      Conclusion: This study shows a shortage in the implementation of guidelines which
      are important to decrease antibiotic resistance and improving clinical outcomes.
      The clinical Pharmacist needs to be more involved in antibiotics prescription
      with the aim of improving effectiveness and decreasing potential antimicrobial
      resistance in hospital settings.

PMID- 30202213
TI  - A comprehensive review on Brigatinib - A wonder drug for targeted cancer therapy
      in non-small cell lung cancer.
AB  - The mortality rate in patients suffering from non-small cell lung cancer (NSCLC)
      is quite high. This type of cancer mainly occurs due to rearrangements in the
      anaplastic lymphoma kinase (ALK) gene which leads to form an oncogene of fused
      gene NPM-ALK. Brigatinib is recently approved by FDA in April 2017 as a potent
      tyrosine kinase inhibitor (TKI) for the NSCLC therapy. In the present scenario,
      it is no less than a wonder drug because it is indicated for the treatment of
      advanced stages of metastatic ALK positive NSCLC, a fatal disease to overcome the
      resistance of various other ALK inhibitors such as crizotinib, ceritinib and
      alectinib. In addition to ALK, it is also active against multiple types of
      kinases such as ROS1, Insulin like growth factor-1Receptor and EGFR. It can be
      synthesized by using N-[2-methoxy-4-[4-(dimethylamino) piperidin-1-yl] aniline]
      guanidine and 2,4,5-trichloropyrimidine respectively in two different ways. Its
      structure consists of mainly dimethylphosphine oxide group which is responsible
      for its pharmacological activity. It is active against various cell lines such as
      HCC78, H2228, H23, H358, H838, U937, HepG2 and Karpas- 299. Results of ALTA (ALK
      in Lung Cancer Trial of AP26113) phase 1/2 trial shows that 90 mg of brigatinib
      for 7 days and then 180 mg for next days is effective in the treatment of NSCLC.
      Brigatinib has been shown to have favorable risk benefit profile and is a safer
      drug than the available cytotoxic chemotherapeutic agents. In comparison to other
      FDA approved drugs for the same condition, it causes fewer minor adverse
      reactions which can be easily managed either by changing the dose or by providing
      good supportive care. This article is intended to provide readers with an
      overview of chemistry, pharmacokinetic, pharmacodynamic and safety profile of
      brigatinib, which addresses an unmet medical need.

PMID- 30202215
TI  - Sodium polystyrene sulfonate induced intestinal necrosis; a case report.
AB  - Background: Hyperkalemia is a commonly encountered medical problem. The treatment
      of hyperkalemia involves the use of pharmacological agents with different
      mechanism of actions. Sodium Polystyrene sulfonate (SPS) is a cation-exchange
      resin that exchanges sodium for potassium. In 2009, the United States Food and
      Drug Administration issued warning against the use of SPS with sorbitol due to
      risk of colonic necrosis. We present a case of SPS induced colonic necrosis in
      the absence of sorbitol and risk factors deemed to increase risk of colonic
      necrosis. Case report: Here we report a 64-year old male with past medical
      history of kidney stones who was admitted for treatment of colitis which was
      complicated by septic shock requiring vasopressors. His course was further
      complicated by hyperkalemia attributed to acute kidney injury. One dose 30 gm of
      SPS was administered which normalized his serum potassium. The patient's course
      was complicated by duodenal ulcer, and colonic perforation. The initial pathology
      findings of the resected specimen were suggestive of inflammatory bowel disease
      which resulted in starting patient on mesalamine. The patient then developed
      fistula which was resected and sent for pathology. SPS induced colonic necrosis
      was made based on the pathology findings. Conclusion: SPS is commonly used to
      decrease potassium levels. SPS has been reported to be associated with several
      gastrointestinal complications. FDA issued warning against the use of SPS in
      patients at risk for complications. Here we report a case with SPS induced
      colonic necrosis in the absence of risk factors reported in the literature.

PMID- 30202216
TI  - Rivaroxaban prescribing in a Saudi tertiary care teaching hospital.
AB  - Purpose: This drug utilization review (DUR) aimed to describe the use of
      rivaroxaban in a tertiary care teaching hospital and to audit the hospital
      physicians' prescribing practice. Methods: This study reviewed rivaroxaban
      prescriptions for patients admitted to a tertiary care teaching hospital in
      Riyadh, Saudi Arabia, between October 1, 2016 and January 15, 2017. It included
      all in-patients who received at least one dose of rivaroxaban, using data from
      the hospital's health information system (HIS). Appropriateness of prescribing
      was evaluated based on documented indication, dosing according to the patient's
      renal function for each approved indication, and restriction policy as per
      hospital department. Results: During the study period, a total of 343 rivaroxaban
      prescriptions for 322 patients were identified. Overall, more than 56% of
      rivaroxaban prescriptions met at least one inappropriate criterion. Inappropriate
      dosing per patient's creatinine clearance (CrCl) was recognized in 42% of
      rivaroxaban prescriptions with the majority of these prescriptions issued for
      lower doses in 82.9% of prescriptions and non-approved indications identified in
      14% of rivaroxaban prescriptions. Conclusions: The introduction of oral
      rivaroxaban represents a paradigm shift in anticoagulation management. Future
      longer, larger multi-center research is needed to identify the most effective
      interventions to enhance rivaroxaban knowledge translation and reduce the
      likelihood of inappropriate rivaroxaban prescribing and associated economic and
      side effects sequelae.

PMID- 30202217
TI  - An exploration of parents' knowledge, attitudes and practices towards the use of
      antibiotics in childhood upper respiratory tract infections in a tertiary
      Jordanian Hospital.
AB  - Objectives: The present study aimed to evaluate the parents' knowledge, attitudes
      and practices (KAP) towards the use of antibiotics for childhood upper
      respiratory tract infections (URTIs), at the Jordanian University Hospital.
      Methods: This was a cross-sectional study. During the study period, 1301 parents
      of young children completed a validated - structured questionnaire. Results: Gaps
      in common knowledge related to antibiotics and their use were noted among
      participants. Nearly half of respondents believed that antibiotics are void from
      adverse effects, while 72.4% of them believed that a child should be given an
      antibiotic if it develops fever, even though 60% they were aware that most URTIs
      were viral in nature. Parents reported that they administered antibiotics to
      children without medical advice most of the time for various causes, including
      using a previously prescribed antibiotic for a similar illness (27.1%), or based
      on pharmacist's recommendation (23.8%). Conclusion: The results demonstrated the
      need for educational interventions to increase the awareness of parents about
      antibiotics to reduce inappropriate use and its consequences.

PMID- 30202218
TI  - Vitamin B12 protects against DNA damage induced by hydrochlorothiazide.
AB  - DNA damage induced by hydrochlorothiazide was previously reported in cultured
      human lymphocytes. In this study, we aimed to investigate the harmful effects of
      hydrochlorothiazide on DNA by measuring the spontaneous frequency of sister
      chromatid exchanges (SCEs) in cultured human lymphocytes. We also aimed to
      investigate the possible protection of that damage by vitamin B12. The results
      showed that hydrochlorothiazide (5 ug/mL) significantly increased the frequency
      of sister chromatid exchanges (P < 0.001) in human lymphocytes in comparison with
      control. Additionally, the frequency of hydrochlorothiazide-induced SCEs was
      significantly decreased by co-treatment with vitamin B12 at concentration of 13.5
      ug/mL (P < 0.001). In conclusion, hydrochlorothiazide is genotoxic to human
      lymphocytes and its toxicity is reduced by vitamin B12.

PMID- 30202220
TI  - New derivatives of hydrogenated pyrido[4,3-b]indoles as potential
      neuroprotectors: Synthesis, biological testing and solubility in pharmaceutically
      relevant solvents.
AB  - The derivatives of hydrogenated pyrido[4,3-b]indoles as potential neuroprotectors
      have been synthesized. The different substituents were introduced into position 8
      of the carboline fragment of the molecule: methyl-, methoxy-, fluorine- and
      chlorine-. Biological tests have shown that all the studied compounds can
      modulate glutamate-dependent uptake of calcium ions in rats' cerebral cortex
      synaptosomes. The shake-flask method was used to measure the solubility of the
      compounds in the buffer solution (pH 7.4), hexane and 1-octanol within the
      temperature interval of 293.15-313.15 K. All the derivatives have been found to
      have low solubility (not exceeding 8 ? 10-4 mole fractions) in the mentioned
      solvents. The effect of thermophysical and protolytic properties of the compounds
      on the solubility have been studied and the thermodynamic functions of compounds
      dissolution in the solvents used have been calculated.

PMID- 30202219
TI  - Nanostructured liquid crystalline formulation as a remarkable new drug delivery
      system of anti-epileptic drugs for treating children patients.
AB  - Purpose: Development of a new dosage-form of antiepileptic-drugs appropriated for
      children. Methods: Clonazepam (Cl) was formulated as cubosomal-gel (cub-gel) to
      be used as a patch reservoir through transdermal-route. Cubosomes prepared using
      glycerol-mono-oleate(GMO)/Pluronic-F127(PF127) mixture. An actual-statistical
      design was used to investigate the effect of different stabilizing agents
      (Ethanol and PVA) and surfactant concentration on cubosomes' particle size and
      entrapping-efficiency. The selected formulae were evaluated by testing particle
      morphology, in vitro drug release and stability. Cub-gel was prepared using
      selected cubosome formulae. The optimal cub-gel subjected to in vitro
      dissolution, ex-vivo permeation and skin deposition studies followed by studying
      its pharmacological effect. Results: Using PVA or Et as stabilizers with PF127
      significantly decreases the average cubosomes'PS (352 +/-  2.8 and 264 +/- 2.16
      nm) and increases EE (58.97 +/- 4.57% and 54.21 +/- 3.89%). Cubosomes increase
      the initial release rate of Cl to ensure rapid therapeutic effect (37.39% and
      46.04% in the first hour) followed by a prolonged release till 4 h. Cub-gel
      containing PVA showed significantly higher Cl-transdermal permeation when
      compared to Cl-suspension. Moreover, increases the retention-time (89.57% at 48
      h) and skin-deposition up to 6-times. It also reduces the epileptic seizures and
      alters the behavioral parameters induced by pilocarpine. Conclusions: Cubosomal
      gel could be considered an innovative dosage-form for Cl through the transdermal
      route.

PMID- 30202221
TI  - Antibacterial prophylaxis in pediatric patients with leukemia.
AB  - Background: Bacterial infections in pediatric patients with leukemia are
      associated with increased risks for morbidity and mortality. Few Recommendations
      have been made on the use of antibacterial prophylaxis in pediatrics with acute
      lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML). Objectives: To
      determine the role of antibacterial prophylaxis in pediatric patients with
      leukemia and the most appropriate regimen that can be safely and effectively
      used. Methods: Literature search was conducted independently by 3 reviewers to
      find studies on the safety and effectiveness of antibacterial prophylactic
      regimens. Results: The search strategy resulted in 13 studies; most of them were
      observational studies. The available evidence recommends use of antibiotics with
      Gram-positive bacterial coverage in AML patients. In ALL patients, prophylaxis
      was used during the intensive phases of chemotherapy with ciprofloxacin being
      recommended most commonly. Conclusion: Antibacterial prophylaxis mainly with
      coverage against Gram-positive bacteria is recommended in pediatric patients with
      AML. For ALL patients, prophylaxis may be considered for patients who are
      undergoing intensive chemotherapy phases and are at high risk for infections with
      ciprofloxacin being the most commonly used agent. In general more studies are
      needed to determine the role of antibacterial prophylaxis in pediatric patients
      with leukemia.

PMID- 30202222
TI  - A survey on traditional plants used in Al Khobah village.
AB  - The use of traditional medicine for treatment of various diseases is a common
      practise in most of the developing countries including the Kingdom of Saudi
      Arabia especially in rural areas. In this survey, Al Khobah village was selected
      to study the status of Traditional Medicine. Al Khobah village is located on the
      Southern boarders of the kingdom and characterized by diverse topography and
      moderate weather. The plants with medicinal uses were collected, identified and
      their methods of preparation and uses were recorded. After gathering all these
      information from the local people, literature survey was conducted on each plant
      to get information about pharmacological activities and weather they support the
      traditional use or not. The survey revealed that the uses of some plants are
      consistent with the experimental data in the literature. Some other plants were
      studied; however, they still need pharmacological investigation to prove the
      claimed uses. Other plant did not subject to any scientific investigation.

PMID- 30202223
TI  - Use of herbal extract from Artemisia herba-alba (Shih) in pharmaceutical
      preparations for dental hygiene.
AB  - Antibiotic resistance in bacterial species is opening new avenues to search for
      alternative modes of antimicrobial treatment, medicinal plant extracts being one
      among them. The aim of this study was to access the possibility of medicinal
      plant extract from Shih in the manufacture of pharmaceutical preparations for
      oral hygiene specifically for the prevention and treatment of dental caries due
      to Streptococcus mutans. Antimicrobial effects of crude organic extract of Shih
      on S. mutans isolated from the saliva were examined by taking S. mutans with
      culture media only (-ve control); S. mutans treated with the antibiotic
      gentamicin (+ve control) and S. mutans treated with Shih. Minimal Inhibitory
      Concentration (MIC) and Minimal Bactericidal Concentration (MBC) were
      Determination by Iodonitrotetrazolium chloride (INT) colorimetric assay Time-kill
      dynamic assay was performed using broth microdilution method. The metabolic
      reason behind the bacteriostatic and bactericidal effect were studied by
      measuring the glucose utilization by the microbes, pH as a measure of acid
      production, nucleic acids quantitation to check the DNA status and inhibition of
      water-insoluble glucan synthesis were undertaken. Shih MIC for S. mutans was at
      2.5 mg/ml and MBC was 4 mg/ml. S. mutans bacterial population started reclining
      within 60 min of incubation with Shih at MBC. Utilization of added glucose was
      very high at MIC due to bacteria overcoming the stress, whereas at MBC its
      utilization was less. Accordingly pH also became acidic to 2.9 with MIC and 4.03
      with MBC. There was a great degree of inhibition in the formation of nucleic
      acids indicating this crude extract interferes with DNA replication. Inhibition
      of glucan synthesis was to the tune of 45% as compared to control. Thus we
      conclude that Shih has potentially effective antibacterial activity hence it can
      be proposed as a potentially effective antiplaque and anticariogenic agent in the
      form of mouth wash or gum paint. However, the cytotoxicity of the extract needs
      to be evaluated in in-vitro and in-vivo conditions before it is considered as a
      safe antiplaque and anticariogenic agent.

PMID- 30202225
TI  - Investigation of antioxidant compounds in commercial pomegranate molasses
      products using matrix-solid phase dispersion extraction coupled with HPLC.
AB  - Pomegranate is a well known fruit for its unique flavor, taste and health
      benefits. The medicinal properties of this fruits directly associated with the
      phenolic content present, with great anti-oxidant potential. The research is
      intended to develop matrix solid phase dispersion method (MSPD) and HPLC
      quantification of four major anti-oxidant marker constituents (vitamin C, gallic
      acid, rutin & ellagic acid) in pomegranate molasses samples. The effects of
      several important experimental parameters like type of dispersant, sample
      dispersant ratio, solvents and its volume, time of extraction were investigated.
      A C18 column with the specification (5 um, 250 * 4.0 mm) was used for the
      separation. A gradient flow of mobile phase was selected after many trials
      containing 0.1%, v/v solution of orthophosphoric acid and acetonitrile. The flow
      rate was 1.0 mL/min; and the chromatograms were recorded at 254 nm. The
      validation parameters, like linearity (r2 = 0.9985, 0.9965, 0.9925 & 0.9986),
      accuracy (100.3, 99.5, 100.9 & 101.9%), intra-day precision (%RSD = 1.09, 1.02,
      1.26 & 0.97), inter-day precision (%RSD = 1.32, 0.83, 1.07, & 1.15) LOD (0.07,
      4.50, 0.45 & 0.40 ug/mL), LOQ (0.095, 9.50, 0.85 & 9.5 ug/mL) and robustness (%
      RSD = 0.92, 0.76, 0.81 & 0.83) respectively for vitamin C, gallic acid, rutin &
      ellagic acid, were found satisfactory as per ICH guidelines.

PMID- 30202224
TI  - Evaluation of teratogenicity and genotoxicity induced by kramecyne (KACY).
AB  - Kramecyne (KACY), a polymer isolated from Krameria cytisoides Cav, has anti
      inflammatory, anti-nociceptive, anti-arthritic and anti-ulcerogenic properties.
      As a part of standard preclinical safety tests, the present study sought to
      determine potential developmental toxicity (in female rats) and genotoxicity (in
      male mice) of KACY. Pregnant female rats were divided into six groups: the
      negative control (vehicle), the positive control (250 mg/kg of acetylsalicylic
      acid (ASA)), and four experimental groups (50, 250, 500 and 1000 mg/kg of KACY).
      To evaluate genotoxicity by in vivo micronuclei (MN) and sister chromatid
      exchange (SCE) tests, male mice were divided into five groups: the negative
      control (vehicle), the positive control (1.5 and 2.5 mg/kg of doxorubicin for MN
      and SCE, respectively), and three experimental groups (50, 500 and 1000 mg/kg of
      KACY). All treatments were administered by oral gavage. A slight maternal
      toxicity was evidenced by lower weight gain for rats receiving 500 and 1000 mg/kg
      of KACY, but no fetal malformations were found. However, there were less live
      fetuses/litter and greater post-implantation loss/litter at these two doses.
      Manifestations of developmental toxicity were limited to a higher rate of
      skeletal alterations. The MN tests did not evidence genotoxicity or cytotoxicity.
      KACY caused a slightly but significantly increased frequency of SCE. Although
      KACY-treated rats had skeletal alterations, these apparently were not caused by a
      mechanism of genotoxicity. Furthermore, the same administration in adult male
      mice did not produce genotoxicity. Hence, KACY herein proved to be safe for rats
      during the period of organogenesis.

PMID- 30202226
TI  - Novel in-situ gel for intravesical administration of ketorolac.
AB  - The urinary bladder stores urine until the time of urination. Systemic
      administration of drugs to treat bladder diseases faces several limitations.
      Therefore, intravesical drug delivery is a promising alternative route of
      administration. An in-situ gel is used to form a gel inside the bladder cavity
      and ensure continuous release of the drug even after urination. The objective of
      the present study was to optimize an in-situ gel formulation of poloxamer and
      chitosan for intravesical delivery of ketorolac tromethamine. The gelling
      temperature of the prepared combinations ranged from 20.67 to 25.8  degrees C. In
      vitro release of KT was sustained for up to 7 h using a poloxamer concentration
      ranging from 17% to 19% and a chitosan concentration ranging from 1% to 2%.
      Design-Expert(r) 10 was used to select the optimized formulation
      (poloxamer/chitosan 17/1.589% w/w) which significantly (p < 0.05) extended the
      drug release more than each polymer alone. An ex-vivo study showed the ability of
      the optimized formulation to sustain drug release after emptying two times to
      mimic urination. Furthermore, the formed gel adhered to the bladder tissue
      throughout the time period of the experiment. Intravesical administration of the
      optimized formulation to rabbits via catheter showed no obstruction of urine flow
      and continuous release of the drug for 12 h.

PMID- 30202227
TI  - Synthesis, biological evaluation and in silico molecular docking of novel 1
      hydroxy-naphthyl substituted heterocycles.
AB  - The versatile precursor 2-acetyl-4-allyl-1-hydroxy naphthalene was synthesized
      efficiently via Claisen rearrangement 2-acetyl-1-allyloxynaphthalene. The Claisen
      Schmidt condensation of latter precursor afforded the corresponding chalcones
      which were exploited to synthesize a series of potential heterocycles such as
      pyrazoline, isoxazoline, benzocoumarin and benzoflavone. The synthesized products
      showed potent antioxidant and antimicrobial activities. Chalcone 3c, naphthyl
      pyrazoline 6b and hydroxycoumarin 13 exhibited the highest activity as
      antioxidants. Their binding mode showed specialized recognition of
      hydroxycoumarin 13 with the triad key amino acids at the active site of the
      oxidoreductase enzyme (PDB code 1DXO). 1-Hydroxynaphth-2-yl pyrazoline (6b)
      revealed the highest efficacy against both Gram positive and negative bacterial
      species. In silico molecular docking of pyrazoline 6b endorsed its proper binding
      at the active site of the 2EX6 enzyme which explains its potent antibacterial
      activity in comparison with standard ampicillin.

PMID- 30202228
TI  - Mosquito and tick repellency of two Anthemis essential oils from Saudi Arabia.
AB  - The essential oils (EOs) of Anthemis melampodina (Am) and Anthemis scrobicularis
      (As) (Asteraceae) were extracted from the aerial parts of the plants by
      hydrodistillation, and their chemical compositions were analyzed using GC-FID and
      GC-MS. Fifty-six components representing 85.5% of the oil composition of Anthemis
      melampdina were identified, and the major components were alpha-pinene (17.1%)
      and beta-eudesmol (13.8%). Forty-one components representing 86% of the oil
      composition of Anthemis scrobicularis were identified, and the major component
      was beta-eudesmol (12.8%). Laboratory bioassays were conducted to determine
      repellency of Am and As EOs against the yellow fever mosquito Aedes aegypti L.
      and the lone star tick Amblyomma americanum L. The minimum effective doses (MEDs)
      of the Am and As EOs against mosquitoes were 0.187 +/- 0.000 and 0.312 +/- 0.063
      mg/cm2 respectively, which were significantly higher than that of DEET (0.023 +/-
      0.000 mg/cm2) in human-based repellent bioassays. The As EO was more repellent
      than Am EO against nymphal ticks but was less effective than DEET in vertical
      paper bioassays.

PMID- 30202229
TI  - Evaluating the preceptor-preceptee relationship among Pharm D students at the
      King Saud University School of Pharmacy.
AB  - Objective: To evaluate preceptee satisfaction concerning preceptorship and the
      preceptor-preceptee relationship among pharmacy students. Methods: A cross
      sectional study was conducted from May 2017 to August 2017 on senior Pharm D
      students at King Saud University (KSU) College of Pharmacy. A survey instrument
      was used to get feedback from students regarding their clinical rotations and
      internships and to evaluate their satisfaction toward preceptorship to meet the
      goals of the curriculum. Data were entered into SPSS, version 24. Results: Of the
      52 students surveyed, 36 (69.2%) were female. More than half of respondents were
      somewhat satisfied with their preceptors and 11.5% were satisfied. Additionally,
      only 17% of students rated their preceptors as having excellent clinical teaching
      skills; about 19% of students rated them as "needs improvement." About 40% of
      students rated their preceptors as very good, concerned, competent, and safe in
      their care for persons living with serious co-morbidities and diseases. About
      half of students (48.1%) rated their non-faculty KSU preceptors' teaching
      behavior as not satisfactory compared with only four respondents with respect to
      KSU faculty preceptors' teaching behavior. Conclusion: Pharm D students were
      somewhat satisfied with their preceptors' teaching behaviors in communication
      skills, practice, and teaching skills as well as feedback and evaluation to
      students. To enhance the quality of experiential education, preceptors should be
      trained to develop programs that direct and energize advancement.

PMID- 30202230
TI  - Synthesis, characterization and antibacterial activity of novel heterocycle,
      coumacine, and two of its derivatives.
AB  - Heterocyclic nucleus plays a fundamental role in the medicinal chemistry and
      serves as a key template for the development of various therapeutic agents
      including broad spectrum antibacterial drugs. In an effort to develop new
      antibacterial agents, a bicyclic twelve-membered heterocyclic nucleus derived
      from coumarin was prepared by an uncomplicated method. The rate of ring closure
      for this nucleus, which was given the name coumacine, in addition to two of its
      derivatives was monitored spectroscopically and this rate followed zero order
      kinetics. The chemical structures of the synthesized products were established by
      detecting their physicochemical properties and analyzing their IR, 1H NMR and 13C
      NMR spectra. The in vitro antibacterial activity of coumacines was evaluated via
      agar dilution method against different standard aerobic and anaerobic bacterial
      strains using ciprofloxacin and metronidazole as positive controls, respectively;
      the results indicated that coumacine I has an excellent broad spectrum
      antibacterial activity against the tested bacterial strains with percentage of
      growth inhibition approximating to those of positive controls.

PMID- 30202231
TI  - Resveratrol-loaded PLGA nanoparticles mediated programmed cell death in prostate
      cancer cells.
AB  - Resveratrol (RL), a natural polyphenol, is known for its diverse biological
      effects against various human cancer cell lines. But low aqueous solubility, poor
      bioavailability, and stability limit its efficacy against prostate cancer. In
      this study polymeric nanoparticles encapsulating resveratrol (RLPLGA) were
      designed and their cytotoxic and mode of apoptotic cells death against prostate
      cancer cell line (LNCaP) was determined. Nanoparticles were prepared by solvent
      displacement method and characterized for particle size, TEM, entrapment
      efficiency, DSC and drug release study. RLPLGA exhibited a significant decrease
      in cell viability with 50% and 90% inhibitory concentration (IC50 and IC90) of
      15.6 +/- 1.49 and 41.1 +/- 2.19 MUM respectively against the LNCaP cells. This
      effect was mediated by apoptosis as confirmed by cell cycle arrest at G1-S
      transition phase, externalization of phosphatidylserine, DNA nicking, loss of
      mitochondrial membrane potential and reactive oxygen species generation in LNCaP
      cells. Furthermore, significantly greater cytotoxicity to LNCaP cells was
      observed with nanoparticles as compared to that of free RL at all tested
      concentrations. RLPLGA nanoparticles presented no adverse cytotoxic effects on
      murine macrophages even at 200 MUM. Our findings support the potential use of
      developed resveratrol loaded nanoparticle for the prostate cancer
      chemoprevention/ chemotherapy with no adverse effect on normal cells.

PMID- 30202233
TI  - Anticandidal activity of the extract and compounds isolated from Cyperus
      conglomertus Rottb.
AB  - The phytochemical screening of Cyperus conglomeratus showed that carbohydrates
      and/or glycosides, flavonoids, tannins, sterols and/or triterpenes, and proteins
      and/or amino acids are present. The fatty acid profile comprised major; palmitic,
      oleic, heptadecanoic, linoleic and minor; arachidonic, lignoceric, stearic, and
      myristic acid. Two compounds; namely, alpha-amyrin and beta-sitosterol were
      isolated by the fractionation of unsaponifiable matter. The acute toxicity study
      showed that the reported after oral administration of the alcohol extract (TAE)
      showed that the plant was highly safe as the LD50 was more than 4000 mg/kg. These
      results were well supported by the sub-chronic toxicity, as the TAE administrated
      to rats for 15 consecutive days at dose 1000 mg/kg showed no alteration in the
      liver and kidney functions. Moreover, the extract of the plant exhibited anti
      candidal activity against different Candida species. The most potent activity,
      (23.1 +/- 2.1, 0.98 ug/ml) and (22.3 +/- 0.53, 0.98 ug/ml), was obtained by the
      chloroform and total extract, respectively against Candida albicans.

PMID- 30202232
TI  - Self-medication practice in pregnant women from central Mexico.
AB  - Self-medication during pregnancy represents a serious threat for mother and child
      health. The objective of this study was to evaluate the prevalence and the
      factors associated with self-medication among Mexican women living in the central
      region of Mexico. This is a descriptive interview-study of 1798 pregnant women or
      women who were pregnant no more than 3 years ago, when the interview was carried
      out. Data analysis was carried out with chi-square analysis and odds ratio. The
      prevalence of self-medication (allopathic drugs, medicinal plants, and other
      products, including vitamins, food supplements, among others) was 21.9%. The
      factors associated (p < 0.05) with self-medication were: higher education
      (college and postgraduate), smoking, and consumption of alcohol. Smoking was the
      strongest factor (OR: 2.536; 1.46-4.42) associated to self-medication during
      pregnancy, followed by consumption of alcohol (OR: 2.06; 1.38-3.08), and higher
      education (OR: 1.607; 1.18-2.19). Medicinal plant consumption was associated with
      nausea, constipation, migraine, and cold (p < 0.05), whereas he self-medication
      of allopathy was associated with gastritis and migraine (p < 0.05). Self
      medication was influenced mainly by a relative or friend, who recommended the use
      of herbal medicine/allopathic medication. Two of the most common medicinal plants
      (arnica and ruda) here informed are reported to induce abortion or toxicity
      during pregnancy. The findings showed that self-medication (medicinal plants and
      allopathic medication) is a common practice among pregnant women from central
      Mexico. Adequate counselling of pregnant women by healthcare professionals about
      the potential risks of self-medication with herbal medicine and allopathic drugs
      during pregnancy is strongly warranted.

PMID- 30202234
TI  - Reduction of Animal Sacrifice in Biomedical Science & Research through
      Alternative Design of Animal Experiments.
AB  - Various upcoming techniques can be used in replacement of experiments requiring
      animal sacrifice or products of animal sacrifice. In many instances these
      techniques provide more reproducibility and control of parameter, compared to
      experiments involving animal or animal products. Use of these techniques can
      avoid the question of the animal sacrifice during experiment and subsequently
      permission of ethical approval. In silico simulation, informatics, 3D cell
      culture models, organ-on-chips are some innovative technology which can reduce
      the number of animals sacrifice. Scientist evolved some innovative culture
      procedures and production of animal friendly affinity reagents which are free
      from the product of animal sacrifice. Direct investigation on human body for
      treatment as well as further research, electronic health record is also helpful
      in the reduction of animals sacrifice in biomedical investigations. These
      techniques and strategies of research can be more cost effective as well as more
      relevant to various issues related to the human health. Some medical blunder has
      also been reported after the successful testing of drugs on animal's model.
      Hence, the reliability of animal experiment in context with human health is
      questionable. Alternative to animal experiments help to reduce the number of
      animals required for research up to certain extent but is not able to eliminate
      the need for animals in research completely. Wisely use of animals in teaching &
      research is expected and the importance of animal experimentation in futuristic
      development in life science cannot be ignored.

PMID- 30202235
TI  - The role of SAMHD1 expression and its relation to HIV-2 (Vpx) gene production.
AB  - SAMHD1 (sterile alpha motif and HD domain 1) is a protein that is found in
      myeloid cells, which restricts HIV1 replication. It depletes the de-oxy
      nucleoside tri-phosphate (dNTPs) pool needed for a viral cDNA synthesis leading
      to inhibition of viral replication inside the cells. However, it does not
      restrict HIV2 replication in myeloid cells due to the presence of viral Vpx
      protein. Vpx is a virion-associated protein which augments viral infectivity and
      it only exists in HIV2 and it has been recently shown in Simian Immunodeficiency
      Virus (SIV) and which can induce degradation of SAMHD1 protein. This increases
      the amount of dNTPs for viral reverse transcription in cytoplasm and HIV
      infection. HIV2 reverse transcription is believed to be less active than HIV1 and
      this could be the reason for the absence of Vpx from HIV1. Protein expression and
      interaction between Vpx and SAMHD1 remains unclear. The interaction of SAMHD1 and
      HIV2-VPx patients' cells can be considered as a first step to help in the
      development for more effective anti-HIV drugs and possible novel intervention
      therapy in the future. Present review article provides comprehensive insights on
      the above issue. We performed a comprehensive literature search in the
      bibliographic database "Pubmed," looking at studies discussing the SAMHDI and Vpx
      interactions.

PMID- 30202236
TI  - Comparison of virulence gene profiles and genomic fingerprints of Vibrio cholerae
      O1 and non-O1/non-O139 isolates from diarrheal patients in southern Thailand.
AB  - Background: Vibrio cholerae is associated with severe watery diarrheal disease
      among people in many parts of the world, including the coastal provinces of
      Southern Thailand. There are relatively few studies focusing on the genetic
      characterization among V. cholerae isolates in this region. Therefore, this study
      aimed at exploring the presence of virulence genes and DNA fingerprints among V.
      cholerae O1 and non-O1/non-O139 isolates obtained from clinical samples in four
      southern coastal provinces during the period of 2001-2009 (n = 21). Results: All
      V. cholerae O1 isolates possessed ctxA, tcpA, zot, ace, hlyA, and vasH genes.
      However, only hlyA, vcsV2, and vasH genes were detected in the majority of the
      non-O1/non-O139 isolates. All O1 isolates showed indistinguishable PCR
      fingerprints by arbitrarily primed (AP)-PCR and enterobacterial repetitive
      intergenic consensus (ERIC)-PCR regardless of the geographical area and period of
      isolation. However, the multi-locus variable-number of tandem-repeat analysis
      (MLVA) could differentiate these O1 isolates (n = 11) into eight profiles.
      Isolates exhibiting an undistinguished MLVA profile also showed identical pulsed
      field gel electrophoresis (PFGE). In addition, the O1 isolates were grouped into
      the same cluster by all methods used in this study. Conclusions: This study
      demonstrated the presence of virulence genes and genetic diversity among
      different serogroups of V. cholerae isolates from clinical samples in southern
      Thailand. V. cholerae O1 isolated over a period of multiple years were
      genetically related, suggesting that they had a clonal origin, whereas non-O1/non
      O139 isolates could have evolved independently.

PMID- 30202237
TI  - Context Based Image Analysis With Application in Dietary Assessment and
      Evaluation.
AB  - Dietary assessment is essential for understanding the link between diet and
      health. We develop a context based image analysis system for dietary assessment
      to automatically segment, identify and quantify food items from images. In this
      paper, we describe image segmentation and object classification methods used in
      our system to detect and identify food items. We then use context information to
      refine the classification results. We define contextual dietary information as
      the data that is not directly produced by the visual appearance of an object in
      the image, but yields information about a user's diet or can be used for diet
      planning. We integrate contextual dietary information that a user supplies to the
      system either explicitly or implicitly to correct potential misclassifications.
      We evaluate our models using food image datasets collected during dietary
      assessment studies from natural eating events.

PMID- 30202238
TI  - Downregulation of hypermethylated in cancer-1 by miR-4532 promotes adriamycin
      resistance in breast cancer cells.
AB  - Background: MicroRNAs are small RNAs (~ 22 nt) that modulate the expression of
      thousands of genes in tumors and play important roles in the formation of
      multidrug resistance. In this study, we firstly investigated that miR-4532
      involved in the multidrug resistance formation of breast cancer by targeting
      hypermethylated in cancer 1 (HIC-1), a tumor-suppressor gene. Methods: To
      identify and characterize the possible miRNAs in regulating multidrug resistance,
      we employed the transcriptome sequencing approach to profile the changes in the
      expression of miRNAs and their target mRNAs were obtained by bioinformatics
      prediction. Then the molecular biology experiments were conducted to confirm miR
      4532 involved in multidrug resistance formation of breast cancer. Results: The
      luciferase reporter assay experiment was employed to confirm that HIC-1 was the
      target of miR-4532. Transfection with an miR-4532 mimic indicated miR-4532 mimic
      significantly increased breast cancer cell resistance to adriamycin. Cell
      proliferation and invasion assay experiments showed overexpression of HIC-1
      inhibited the invasion and metastasis of breast cancer cells. Meanwhile, the
      interleukin (IL)-6/signal transducer and activator of transcription 3 (STAT3)
      signaling pathway was confirmed to be involving in multidrug resistance by
      western blotting experiments. Conclusions: These results suggest that
      downregulation of hypermethylated in cancer-1 by miR-4532 could promote
      adriamycin resistance in breast cancer cells, in which the IL-6/STAT3 pathway was
      regulated by the HIC-1. This finding might contribute to new therapeutic target
      for reversal of tumor resistance.

PMID- 30202239
TI  - Sulbactam-enhanced cytotoxicity of doxorubicin in breast cancer cells.
AB  - Background: Multidrug resistance (MDR) is a major obstacle in breast cancer
      treatment. The predominant mechanism underlying MDR is an increase in the
      activity of adenosine triphosphate (ATP)-dependent drug efflux transporters.
      Sulbactam, a beta-lactamase inhibitor, is generally combined with beta-lactam
      antibiotics for treating bacterial infections. However, sulbactam alone can be
      used to treat Acinetobacter baumannii infections because it inhibits the
      expression of ATP-binding cassette (ABC) transporter proteins. This is the first
      study to report the effects of sulbactam on mammalian cells. Methods: We used the
      breast cancer cell lines as a model system to determine whether sulbactam affects
      cancer cells. The cell viabilities in the present of doxorubicin with or without
      sulbactam were measured by MTT assay. Protein identities and the changes in
      protein expression levels in the cells after sulbactam and doxorubicin treatment
      were determined using LC-MS/MS. Real-time reverse transcription polymerase chain
      reaction (real-time RT-PCR) was used to analyze the change in mRNA expression
      levels of ABC transporters after treatment of doxorubicin with or without
      sulbactam. The efflux of doxorubicin was measures by the doxorubicin efflux
      assay. Results: MTT assay revealed that sulbactam enhanced the cytotoxicity of
      doxorubicin in breast cancer cells. The results of proteomics showed that ABC
      transporter proteins and proteins associated with the process of transcription
      and initiation of translation were reduced. The mRNA expression levels of ABC
      transporters were also decreased when treated with doxorubicin and sulbactam. The
      doxorubicin efflux assay showed that sulbactam treatment inhibited doxorubicin
      efflux. Conclusions: The combination of sulbactam and doxorubicin enhances the
      cytotoxicity of doxorubicin in the breast cancer cells by inhibiting the
      expression of ABC transporter proteins and proteins associated with the process
      of transcription and initiation of translation, and blocking the efflux of
      doxorubicin. Co-treatment of doxorubicin and sulbactam can be used in breast
      cancer treatment to decrease the prescribed dose of doxorubicin to avoid the
      adverse effects of doxorubicin.

PMID- 30202240
TI  - SOX2OT knockdown derived changes in mitotic regulatory gene network of cancer
      cells.
AB  - Background: SOX2 overlapping transcript (SOX2OT) is a long non-coding RNA, over
      expressed in human tumor tissues and embryonic cells. Evidences support its
      function in the cell cycle; however there is no clear mechanism explaining its
      function in cell proliferation regulation. Here we investigated cancer cell
      response to SOX2OT knockdown by RNA sequencing. Methods: SOX2OT expression was
      inhibited by siRNA in two cancer cell lines (A549, U-87 MG), then the RNA of
      treated cells were used for the cDNA library synthesis and RNA sequencing. The
      differentially expressed genes were used for functional enrichment and the gene
      expression network was analyzed to find the most relevant biological process with
      SOX2OT function. Furthermore, the expression change of candidate genes was
      measured by qRT-PCR for more confirmation and the cell cycle was monitored by PI
      staining. Results: Our findings showed that SOX2OT knockdown affects the cellular
      gene expression generally with enriched cell proliferation and development
      biological process. Particularly, the cell cycle and mitotic regulatory genes
      expression including: CDK2, CDK2AP2, ACTR3, and chromosome structure associated
      genes like SMC4, INCENP and GNL3L are changed in treated cancer cells.
      Conclusion: Our results propound SOX2OT association with cell cycle and mitosis
      regulation in cancer cells.

PMID- 30202243
TI  - SH2B1 promotes NSCLC cell proliferation through PI3K/Akt/mTOR signaling cascade.
AB  - Background: Non-small cell lung cancer (NSCLC), 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. The objective of this study was to investigate
      the role SH2B1 and the underlying molecular mechanism in NSCLC. Methods: Cell
      functional analysis and cell line-derived xenograft model were performed to
      determine SH2B1 potential roles on NSCLC cell proliferation in vitro and in vivo.
      In vitro assays were performed to identify signal molecular mechanisms.
      Subsequently, 104 patients with NSCLC undergoing primary surgical resection were
      recruited to evaluated expression of SH2B1 and Akt/mTOR signaling markers by
      immunohistochemical staining to determine their clinicopathologic significance.
      Results: Modulation of SH2B1 expression levels had distinct effects on cell
      proliferation, cell cycle and apoptosis in the NSCLC cell lines A549 and H1299.
      At the molecular level, overexpression of SH2B1 resulted in the upregulation of
      the Akt/mTOR markers, p-Akt and p-mTOR, and downregulation of PTEN to promote
      NSCLC cell proliferation, while silencing SH2B1 had the opposite effect. In human
      NSCLC specimens, SH2B1 expression levels were positively associated with Akt/mTOR
      signaling pathway markers. Conclusions: The SH2B1/Akt/mTOR/PTEN axis is required
      for regulating NSCLC cell proliferation and might prove to be a promising
      strategy for restraining tumor progression in NSCLC patients.

PMID- 30202242
TI  - Assessment of intratumor immune-microenvironment in colorectal cancers with
      extranodal extension of nodal metastases.
AB  - Background: No data is available on the molecular background of the extra-nodal
      extension (ENE) of lymph node metastasis (LN) in colorectal cancer (CRC).
      Methods: A series of 22 ENE-positive CRCs was considered and three samples per
      case were selected (the primary CRC, an ENE-negative and an ENE-positive
      metastatic LN). Samples (n = 66) were analysed by immunohistochemistry for PD-L1,
      CD4, CD8, CD68 and CD80. Fifteen out of twenty-two cases were further profiled
      through a hotspot multigene mutational custom panel, including 164 hotspot
      regions of AKT1, APC, BRAF, CTNNB1, KIT, KRAS, NRAS, PDGFRA, PIK3CA, PTEN and
      TP53 genes. Results: A significantly higher percentage of CD4-, CD8- and CD68
      positive cells was observed at the invasive front of both CRCs and in ENE in
      contrast with what observed at the core of both CRCs and their matched nodal
      metastases. ENE was also characterized by a significantly higher number of CD80
      positive cells. No significant difference was observed in PD-L1 distribution
      among the different specimens. Fourteen out of 15 CRCs (93%) showed at least a
      driver mutation. The most frequently mutated gene was TP53 (n = 8 tumors),
      followed by APC (n = 6), BRAF (n = 4), KRAS, NRAS and PIK3CA (n = 2). In 11 out
      of 15 CRCs (73%) the mutational profiling of the primary tumor was consistent
      with what obtained from the two matched LNs. Conclusions: A heterogeneous
      intratumor immune-microenvironment has been observed in ENE-positive CRCs, which
      are characterized by an increased leukocytic infiltration at the ENE invasive
      front.

PMID- 30202244
TI  - Expression and clinical significance of the NEK7-NLRP3 inflammasome signaling
      pathway in patients with systemic lupus erythematosus.
AB  - Background: The aim of the study was to investigate the expression of the NEK7
      NLRP3 inflammasome signaling pathway in the peripheral blood mononuclear cells
      (PBMCs) of patients with systemic lupus erythematosus (SLE), as well as its
      clinical significance. Methods: A total of 38 SLE patients and 33 healthy
      volunteers were recruited. Real time PCR and western blotting were performed to
      determine mRNA and protein levels of NEK7, NLRP3 inflammasome components (NLRP3,
      ASC, and Caspase-1), and downstream cytokines (IL-1b and IL-18) in PBMCs from the
      two groups. ELISA was used to detect serum levels of IL-1b and IL-18. The same
      methods were used to detect changes in the above indices in the 25 SLE patients
      after treatment. Correlations between clinical and laboratory parameters were
      also analyzed. Results: Compared to those in healthy controls, levels of NEK7,
      NLPR3, and ASC were lower in SLE patients; however, Caspase-1, IL-1b, and IL-18
      were expressed at higher levels. mRNA levels of NEK7, NLRP3, and ASC were
      inversely correlated with disease activity, whereas a positive correlation was
      observed with IL-1b and IL-18. After treatment, mRNA levels of NEK7 and NLRP3
      increased, whereas Caspase-1, IL-1b, and IL-18 decreased significantly. Compared
      to those in SLE patients without renal damage, patients with lupus nephritis (LN)
      exhibited lower mRNA levels of NEK7, NLRP3, and ASC but higher levels of Caspase
      1, IL-1b, and IL-18. Conclusions: Results indicate that the expression of the
      NEK7-NLRP3 complex might play a protective role in the pathogenesis of SLE and is
      inversely correlated with disease activity. A positive effect of NEK7 on NLRP3
      was observed, and the low expression of NLRP3 in SLE patients might be related to
      the low expression of NEK7. Overexpression of Caspase-1 in SLE patients mediates
      the maturation and release of IL-1b and IL-18, and contributes to the
      pathogenesis of SLE and LN.

PMID- 30202246
TI  - A Study and Development of Workplace Facilities and Working Environment to
      Increase the Work Efficiency of Persons with Disabilities: A Case Study of Major
      Retail and Wholesale Companies in Bangkok.
AB  - This research aims to improve the work effectiveness of people with physical
      disabilities in department stores, retail and wholesale companies in Bangkok. It
      focuses on the environment and facilities needed by people with three types of
      disabilities, visual impairment, hearing impairment, and wheelchair users. A
      mixed research method was used (questionnaires, interviews, and observations).
      The results were applied to a design process based on the needs of people with
      physical disabilities and addressed solving their work problems, increasing their
      work effectiveness, and bringing the results of the design to a group discussion.
      The group was made up of 15 experts who were supervisors, representatives of the
      people with each type of physical disability, instructors, and personnel from the
      university knowledgeable about universal design for people with disabilities.
      Architects and designers helped to brainstorm ideas and develop designs that led
      to production and product testing. Testing was conducted to compare pretest and
      posttest results using designed products to evaluate the work effectiveness of
      the people with physical disabilities using statistical analysis (paired t
      tests). The results using developed products showed a higher average posttest
      score than pretest. This indicated a statistically higher work effectiveness
      (alpha =0.05) and supports the research hypothesis.

PMID- 30202241
TI  - Effect of dietary components on miRNA and colorectal carcinogenesis.
AB  - Background: Colorectal cancer (CRC) is one of the most common cancers diagnosed
      and among the commonest causes of cancer-related mortality globally. Despite the
      various available treatment options, millions of people still suffer from this
      illness and most of these treatment options have several limitations. Therefore,
      a less expensive, non-invasive or a treatment that requires the use of dietary
      products remains a focal point in this review. Main body: Aberrant microRNA
      expression has been revealed to have a functional role in the initiation and
      progression of CRC. These has shown significant promise in the diagnosis and
      prognosis of CRC, owing to their unique expression profile associated with cancer
      types and malignancies. Moreover, microRNA therapeutics show a great promise in
      preclinical studies, and these encourage further development of their clinical
      use in CRC patients. Additionally, emerging studies show the chemo-preventive
      potential of dietary components in microRNA modulation using several CRC models.
      This review examines the dietary interplay between microRNAs and CRC incidence.
      Improving the understanding of the interactions between microRNAs and dietary
      components in the carcinogenesis of CRC will assist the study of CRC progression
      and finally, in developing personalized approaches for cancer prevention and
      therapy. Conclusion: Although miRNA research is still at its infancy, it could
      serve as a promising predictive biomarkers and therapeutic targets for CRC. Given
      the ever-expanding number of miRNAs, understanding their functional aspects
      represents a promising option for further research.

PMID- 30202245
TI  - Does Deployment-Related Military Sexual Assault Interact with Combat Exposure to
      Predict Posttraumatic Stress Disorder in Female Veterans?
AB  - The objective of the present research was to expand upon previous findings
      indicating that military sexual trauma interacts with combat exposure to predict
      PTSD among female Iraq/Afghanistan-era veterans. Three hundred and thirty female
      veterans completed self-report measures of combat experiences, military sexual
      assault (MSA) experiences, and PTSD symptoms as well as structured diagnostic
      interviews for PTSD. A significant strength of the present research was the use
      of PTSD diagnosis as an outcome measure. Consistent with prior research, both
      combat exposure and MSA were significant predictors of PTSD symptoms (linear
      regression) and PTSD diagnoses (logistic regression). Specifically, participants
      who experienced deployment-related MSA had approximately six times the odds of
      developing PTSD compared to those who had not experienced deployment-related MSA,
      over and above the effects of combat exposure. Contrary to expectations, the
      hypothesized interaction between MSA and combat exposure was not significant in
      any of the models. The low base rate of MSA may have limited power to find a
      significant interaction; however, these findings are also consistent with other
      recent studies that have failed to find support for the hypothesized interaction.
      Thus, whereas the majority of available evidence indicates that MSA increases
      risk for PTSD among veterans over and above the effects of combat, there is
      presently only limited support for the hypothesized MSA x combat interaction.
      These findings highlight the continued need for prevention and treatment of MSA
      in order to improve veterans' long-term mental health and well-being.

PMID- 30202247
TI  - A Streaming Motion Magnification Core for Smart Image Sensors.
AB  - This paper proposes a modified Eulerian Video Magnification (EVM) algorithm and a
      hardware implementation of a motion magnification core for smart image sensors.
      Compared to the original EVM algorithm, we perform the pixel-wise temporal
      bandpass filtering only once rather than multiple times on all scale layers, to
      reduce the memory and multiplier requirement for hardware implementation. A pixel
      stream processing architecture with pipelined blocks is proposed for the
      magnification core, enabling it to readily fit common image sensing components
      with streaming pixel output, while achieving higher performance with lower system
      cost. We implemented an FPGA-based prototype that is able to process up to 90M
      pixels per second and magnify subtle motion. The motion magnification results are
      comparable to the original algorithm running on PC.

PMID- 30202249
TI  - Effect of Health-Promoting Agents on Exclusion-Zone Size.
AB  - It is now well-confirmed that hydrophilic surfaces including those within the
      cell generate structural changes in water. This interfacial water is ordered and
      acquires features different from the bulk. Amongst those features is the
      exclusion of colloidal and molecular solutes from extensive regions next to the
      hydrophilic surface, thereby earning it the label of "exclusion zone" (EZ) water.
      The transition of ordered EZ water to bulk serves as an important trigger of many
      cellular physiological functions, and in turn cellular health. We tested
      physiological doses of half a dozen agents generally identified to restore or
      build health on the extent to which they build EZs. All agents known to enhance
      biological function resulted in EZ expansion. On the other hand, the weed killer,
      glyphosate, considerably diminished EZ size. While the expansion effect of the
      health-promoting agents was observed over a wide range of concentrations,
      excessive doses ultimately reduced EZ size. We hypothesize that EZ buildup may be
      a mechanistic feature underlying many health-promoting agents, while agents that
      impair health may act by diminishing the amount of EZ water.

PMID- 30202248
TI  - Assessment Through the Short Physical Performance Battery of the Functionality in
      Individuals With Metabolic Syndrome Exposed to Whole-Body Vibration Exercises.
AB  - Physical activity is recommended in the management of individuals with metabolic
      syndrome (MetS), and recent studies have suggested whole-body vibration exercise
      (WBVe) for this population. The aim of this study was to evaluate the
      functionality through the Short Physical Performance Battery (SPPB) in
      individuals with MetS after WBVe. The SPPB evaluates the balance, the gait speed,
      and the lower limb strength (five-chair stand [5CS] test). Forty-four individuals
      with MetS were divided into WBVe (WBVeG) and control (CG) groups. The individuals
      of the WBVeG performed 10 sessions of WBVe in an oscillating/vibratory platform
      (OVP), barefoot, for 3 minutes at the peak-to-peak displacements of 2.5, 5.0, and
      7.5 mm, with a resting period of 1 minute (total time: 18 minutes/session). The
      frequencies ranged from 5 up to 14 Hz. The individuals of the CG performed all
      the steps of the study, but the OVP was turned off. Before the first and after
      the tenth session, the individuals performed the SPPB. Significant responses were
      found in the WBVeG, analyzing the total score of the SPPB (P = .005), the balance
      test (P = .01), the gait speed (P = .006), and the 5CS test (P = .03), resulting
      in the improvement of the functionality of individuals with MetS.

PMID- 30202250
TI  - Comparing the Acute Effects of Intermittent and Continuous Whole-Body Vibration
      Exposure on Neuromuscular and Functional Measures in Sarcopenia and Nonsarcopenic
      Elderly Women.
AB  - This investigation examined the acute effects of continuous whole-body vibration
      (CWBV) and intermittent whole-body vibration (IWBV) on neuromuscular and
      functional measures in women with sarcopenia and nonsarcopenic women. Continuous
      whole-body vibration was one 6-minute exposure, while IWBV consisted of six 60
      second exposures to rest intervals (30 Hz, 2-4 mm amplitude). Factorial analyses
      revealed group * exposure * time interactions for jump height (JH; F = 10.8, P =
      .002), grip strength (GS; F = 15.5, P < .001), timed up and go test (F = 11.7, P
      = .002), and sit and reach test (S&R; F = 9.7, P = .004). Both JH and GS
      significantly improved post-WBV in women with sarcopenia (P < .001), with post
      IWBV significantly greater (P < .001) than post-CWBV. Timed up and go test and
      S&R significantly improved post-IWBV in both the groups (P < .001) with post-IWBV
      significantly better than post-CWBV (P < .001). Bench press power at 20% one
      repetition maximum (1RM) revealed an exposure * time interaction (F = 4.6, P =
      .04) illuminating that IWBV significantly improved muscular power (P < .001).
      Bench press power at 40% 1RM revealed group * exposure (F = 6.4, P = .016) and
      exposure * time interactions (F = 5.8, P = .022). Individuals with sarcopenia
      significantly increased power output (P < .001) post-IWBV which was significantly
      greater than post-CWBV (P = .037). Bench press power at 60% 1RM revealed an
      exposure * time interaction (F = 8.6, P = .006), indicating that power was
      significantly improved post-IWBV (P = .027) and decreased post-CWBV. Berg Balance
      scale revealed a time main effect (F = 6.64, P = .015), and pain discomfort was
      significantly lower post-IWBV. These data indicate IWBV may provide a more
      efficacious exposure pattern in older women when compared to CWBV.

PMID- 30202251
TI  - High-Intensity Interval Training Combined With Vibration and Dietary Restriction
      Improves Body Composition and Blood Lipids in Obese Adults: A Randomized Trial.
AB  - This study aimed to compare the effect of high-intensity interval training (HIIT)
      with additional whole-body vibration (WBV) on body composition and lipid profile
      in obese/overweight adults on a hypocaloric diet. Forty adults were randomly
      assigned to (a) HIIT and vibration and hypocaloric diet (HIITWBV, n = 13), (b)
      HIIT and diet (HIIT, n = 14), and (c) diet only (control [CON], n = 13). High
      intensity interval training WBV participants trained 3 times per week for 8 weeks
      (6 sets * 1 minute of HIIT, cycling at 90% heart rate peak followed by 1 minute
      of interset vibration, at a frequency of 18 Hz increasing until 25 Hz with a peak
      to-peak displacement of 4 mm. Training volume increased 1 set every 2 weeks until
      10 sets). The HIIT group performed HIIT training followed by 2 minutes of passive
      recovery, while the CON continued with their daily activities combined with
      calorie restriction. Body composition (body fat and fat-free mass) and
      biochemical indices (glucose, total cholesterol, high-density lipoprotein
      cholesterol, and triglycerides) were determined. Following 8 weeks, body fat was
      significantly reduced by 7.5% and both triglycerides and total cholesterol
      decreased in the HIITWBV group only (-16.5% and -11.7% respectively). This study
      suggests that HIIT in combination with WBV and a hypocaloric diet can improve
      overall lipid profile in overweight/obese individuals.

PMID- 30202252
TI  - Time for Lifestyle Medicine to Take Injury Prevention Seriously.
AB  - Over 2 decades ago, the United States National Academy of Sciences described
      injuries as "the most under-recognized major public health problem facing the
      nation." Our progress since then has been limited. Injuries still account for
      nearly 1 out of every 10 deaths in the world, and the global burden of injury is
      projected to increase over the next decade, predominately in low- and middle
      income countries. Despite this, injury prevention receives scant attention from
      legislators, the education system, and, most strikingly, the health care system.
      The lifestyle medicine community, however, is beginning to focus on injury
      prevention and will play an increasing role in helping control the burden of
      injury. Lifestyle medicine practitioners are in a tremendous position to promote
      injury prevention. Physical activity and positive lifestyle changes can be
      accompanied with an increased focus on preventing injury. Lifestyle medicine can
      prevent injuries by supporting legislation, advancing medical advocacy, providing
      community education, and linking clinical care with injury prevention.

PMID- 30202253
TI  - The Changed Injury Landscape, More on Injury Prevention Roles for the Lifestyle
      Physician, and More Than "Limited Progress" Since Injury in America.
AB  - One theme of the article ("Time for Lifestyle Medicine to Take Injury Prevention
      Seriously," by Teitge and Francescutti) that should resonate with contemporary
      injury prevention proponents-whether they are researchers, practitioners, policy
      makers, or advocates in the public health arena or providers, administrators, and
      patient advocates in the health care arena-is the need for an increased injury
      prevention focus among health care providers. In particular, the call for
      providers to link injury prevention approaches and tools to the clinical care of
      patients is both noteworthy and compelling. However, the authors' description of
      the current injury experience in the United States fails to acknowledge important
      changes over the past decade and a half that have had an impact on the injury
      prevention roles of providers. Plus, the notion that progress in injury
      prevention has been limited in the 3 decades since the publication of Injury in
      America, undervalues the advances that have occurred.

PMID- 30202254
TI  - The Difficulty of Prevention: A Behavioral Perspective.
AB  - Behavioral medicine provides insight in to the problem of injury prevention.
      Society often views unintentional injuries as only an accident when in reality
      many accident-related injuries are preventable. However, barriers to behavioral
      change in injury prevention exist for both patients (eg, inconvenience, perceived
      risk-benefit ratio) and health care providers (eg, feeling of badgering
      nonadherent patients, patient misinformation). To overcome barriers, the article
      discusses strategies for health care providers to address injury prevention such
      as choosing active over passive strategies, informing patients of predictable
      injury-prone circumstances, and individualizing patient risks.

PMID- 30202256
TI  - Improve Your Kitchen and Food Safety.

PMID- 30202255
TI  - Potentially Driver-Impairing Medications: Risks and Strategies for Injury
      Prevention.
AB  - Impaired driving is a major cause of motor vehicle accidents, injury, and
      fatality. Several classes of medication have been found to affect a driver's
      cognition, judgment, and reaction time and may put patients at increased risk for
      accidents and injury. This article will explore medications with side effects
      posing a potential threat to drivers, including anxiolytics, sedative hypnotics,
      antihistamines, and antidepressants, as well as describe potential strategies for
      mitigating or minimizing such risks.

PMID- 30202257
TI  - Dietary Guidelines for Americans: Implications for Primary Care Providers.
AB  - In the United States, high rates of obesity and chronic disease impose serious
      consequences on the population's health and health care system. Primary care
      providers are critical to broad prevention efforts aiming to reduce the burden of
      chronic disease in the nation and play an important role in addressing lifestyle
      behaviors that can result in illness and premature death. Unhealthy dietary
      behaviors largely contribute to morbidity and mortality in the United States
      despite national efforts to improve the nutritional quality of the typical
      American diet. This article discusses a comprehensive set of national evidence
      based recommendations known as the Dietary Guidelines for Americans that can
      support primary care providers' efforts to improve patient outcomes through
      optimal nutrition and healthy lifestyle behaviors. This article also describes
      basic behavioral counseling techniques primary care providers can incorporate
      into time-limited patient encounters to help improve the dietary and physical
      activity behaviors of their patients.

PMID- 30202258
TI  - Psychosocial Interventions for Patients With Advanced Cancer and Their Families.
AB  - Few randomized controlled trials of family-based psychosocial interventions
      involving patients and at least one other family member have been conducted in
      the context of advanced cancer. Moreover, existing interventions have largely
      been stand-alone programs that have not been well integrated into routine
      palliative and clinical care. Programs that address this gap may not only improve
      patient and caregiver quality of life (QOL) but also the quality of palliative
      and supportive care services. The aim of this narrative review is to describe
      published interventions that have attempted to improve the QOL of advanced cancer
      patients and their family caregivers (eg, spouses, partners, and other family
      members) and to describe some of the challenges that make it difficult to
      implement such programs in clinical settings. Toward that end, the added value
      that family-based psychosocial interventions can bring to advanced cancer care is
      first described. Next, the literature on family-based interventions in advanced
      cancer is reviewed, and different theoretical approaches and outcomes are
      highlighted. This is followed by a description of some of the health system
      barriers to supportive family care in advanced cancer care. The article concludes
      with a synthesis of research findings and proposes directions for future
      research.

PMID- 30202259
TI  - The Complete Health Improvement Program (CHIP): History, Evaluation, and
      Outcomes.
AB  - The Complete Health Improvement Program (CHIP) is a premier lifestyle
      intervention targeting chronic disease that has been offered for more than 25
      years. The intervention has been used in clinical, corporate, and community
      settings, and the short-term and long-term clinical benefits of the intervention,
      as well as its cost-effectiveness, have been documented in more than 25 peer
      reviewed publications. Being an easily administered intervention, CHIP has been
      presented not only by health professionals but also by non-health-trained
      volunteers. The benefits of the program have been extensively studied under these
      2 delivery channels, consistently demonstrating positive outcomes. This article
      provides a brief history of CHIP and describes the content and structure of the
      intervention. The published evaluations and outcomes of the intervention are
      presented and discussed and future directions are highlighted.

PMID- 30202261
TI  - The Obesities: Various Paradigms Addressing a Single Problem.
AB  - This article provides a commentary on the article titled "The Obesities: An
      Overview of Convergent and Divergent Paradigms" by Karasu. Addressing the concept
      of obesity from various viewpoints, the article reflects the multicausal nature
      of a problem many societies are facing. Despite the ongoing controversy on who is
      to blame for the obesity epidemic, the underlying concept of obesity remains an
      imbalance between energy intake and energy expenditure. These 2 components,
      therefore, need to be considered in synchrony rather than being separated.
      Similarly, the complex interaction between individual, environmental, and
      physiological constraints warrants a multidisciplinary approach to enhance the
      understanding of the regulation of energy balance rather than a separation into
      several different areas of "obesities."

PMID- 30202263
TI  - Gut Microbiota and Obesity: Potential Therapeutic Targets and Probiotic
      Treatment.
AB  - The gut bacteria model attributes obesity to the variable makeup of gut
      microbiota and its ability to modulate host energy homeostasis, adiposity and
      inflammation. To counteract these deleterious effects, strains of probiotics have
      been developed to manipulate gut microbiomes and improve health. The current
      article explores the mechanisms by which gut microbiota modulate host metabolism
      and highlights recent human study data assessing the effects of probiotic
      supplementation on the prevention and treatment of obesity.

PMID- 30202262
TI  - Bridging the Science-Practice Gap in Obesity Treatment.
AB  - The number of putative causes of obesity continues to increase at a rapid rate.
      As science identifies novel causes of obesity, innovations in the treatment of
      obesity also evolve. These innovations have important implications for clinical
      practice; however, a gap exists between research and the clinical application of
      research. Practical considerations about how to address this gap between research
      and practice are discussed.

PMID- 30202260
TI  - The Obesities: An Overview of Convergent and Divergent Paradigms.
AB  - The study of obesity lends itself to difficulties not only due to our imprecise
      ability to measure body composition, food consumption, and physical activity but
      also, even more important, due to complexities involved in defining and
      conceptualizing obesity. For centuries, obesity has been considered a disease,
      although researchers and clinicians cannot agree on definitions of "disease" or,
      if it is one, whether obesity is a disease of metabolism, inflammation, brown
      fat, chronobiology, the blood-brain barrier, the right brain, or even of
      infectious origin. The concept of "obesity" as a disease remains controversial to
      some because not everyone who has excess adipose tissue has any evidence of
      disease. Obesity, though, has also been considered a sin, a crime against
      society, an aesthetic crime, a self-inflicted disability, an example of body
      diversity, a failure in the regulation of energy balance, an appropriate or even
      inappropriate adaptation to our increasingly obesogenic environment, a genetic
      disorder, and a psychological/behavioral disorder of overeating involving self
      regulation or even addiction. Five major paradigms-medical, sociocultural,
      evolutionary, environmental, and psychological/behavioral, all with their own
      subcategorical models-have been identified. All 5 paradigms are required because
      we are dealing not with "obesity" but with a plurality, the "obesities."

PMID- 30202264
TI  - Sizing and Resizing Portions for Better Nutrition and Weight Management.

PMID- 30202265
TI  - Managing Medically Unexplained Symptoms in Primary Care: A Narrative Review and
      Treatment Recommendations.
AB  - Medically unexplained symptoms (MUS) are persistent physical symptoms in the
      absence of identifiable disease. MUS present a major challenge for primary care
      providers (PCPs) because complex symptom presentations, strained patient
      physician relationships, and treatment-resistant symptoms can challenge a PCP's
      sense of competency. This review is intended to help PCPs understand the burden
      and theoretical context of MUS and to provide concise recommendations for
      managing MUS within primary care settings. Based on a narrative review of the
      literature, these recommendations emphasize in particular the importance of co
      creating plausible explanations for MUS, understanding the pitfalls of
      consultations involving MUS, and developing multimodal treatment plans.

PMID- 30202267
TI  - The Influence of Exercise on Perceived Pain and Disability in Patients With
      Lumbar Spinal Stenosis: A Systematic Review of Randomized Controlled Trials.
AB  - Lumbar spinal stenosis (LSS) is an increasingly prevalent condition that has
      major health and economic implications. While there are many options for the
      treatment of LSS, exercise is widely considered a first-line intervention as it
      is associated with reduced complications and cost as compared to more invasive
      options. Currently, it is not clear if exercise is an effective approach to
      managing pain and perceived disability in patients with symptomatic LSS.
      Therefore, the purpose of this systematic review is to evaluate the published
      literature that has investigated exercise as a primary intervention for LSS. A
      search was conducted in electronic databases including PubMed, PEDro,
      SPORTDiscus, CINAHL, and AMED using the key words lumbar spinal stenosis,
      exercise, physical therapy, rehabilitation, and conservative treatment. Inclusion
      criteria consisted of published randomized controlled trials written in English
      that included exercise as the primary treatment in at least one of the groups,
      and had reported measures of pain and disability clearly stated. The search
      identified 310 studies of which 5 met all the inclusion parameters. Exercise
      appears to be an efficacious intervention for pain, disability, analgesic intake,
      depression, anger, and mood disturbance among patients with LSS. Further research
      is needed to determine which type of exercise is the most effective in managing
      symptoms associated with lumbar spinal stenosis.

PMID- 30202269
TI  - Nutritional Immunity: Starving Pathogens of Trace Minerals.
AB  - Nutritional immunity is a process by which a host organism sequesters trace
      minerals in an effort to limit pathogenicity during infection. Circulating
      concentrations of minerals, such as iron and zinc, decline rapidly and
      dramatically with the inflammation associated with infection. The decline in iron
      and zinc is thought to starve invading pathogens of these essential elements,
      limiting disease progression and severity. The mechanisms contributing to the
      hypoferremia and hypozincemia of inflammation and potential interventions that
      exploit this process for the management of infection will be discussed.

PMID- 30202266
TI  - Translating Guidelines for the Diagnosis and Management of Sports-Related
      Concussion Into Practice.
AB  - Sports injuries are a significant clinical and public health concern. There is a
      growing call to improve the translation of available evidence-based and expert
      informed sports injury prevention interventions into sustained use in practice by
      physicians and others (eg, athletic trainers, coaches, and parents) who care for
      injured athletes. This article provides a brief overview of the current sport
      injury prevention implementation literature before focusing specifically on the
      translation of guidelines (including consensus and position statements) developed
      to assist physicians and others diagnose and manage athletes with sport-related
      concussion and the associated return-to-play decisions. The outcomes of more than
      20 published studies indicate that physician, athletic trainer, coach, parent,
      and athlete knowledge, use of, and compliance with sport-related concussion
      guidelines are limited. More concerted, coordinated, and theory-informed efforts
      are required to facilitate the widespread dissemination, translation, and
      implementation of such guidelines. An example is provided of how implementation
      drivers could be used to inform the development of a comprehensive, multilevel
      implementation strategy targeting the individual, organizational, and system
      level changes necessary to support the translation of available sport-related
      concussion guidelines in both the clinical and sports settings.

PMID- 30202270
TI  - Immune Function: Impact of Exercise and Nutritional Interventions.
AB  - This article provides a brief commentary on the accompanying article, "Nutrition
      and Physical Activity Interventions to Improve Immunity" by Davison, Kehaya, and
      Jones. The article reviews the evidence on physical exercise and/or nutrition in
      modulating immune response, with a specific focus on the prevention of
      respiratory infection. Given the large scope of the review, an overview of
      current findings is presented, rather than in-depth discussions, and the
      nutritional strategies discussed tend to focus on the strategies that have been
      studied in the context of exercise. Some further insight is provided in the
      commentary on potential mechanisms that may explain the benefits of exercise, a
      brief discussion on the impact of obesity and host defense, and future directions
      for research. In general, the article sufficiently describes the current
      evidence, and draws appropriate conclusions based on the evidence presented. The
      article is recommended for audiences that have limited background on these
      topics, and for those who are familiar with this line of research.

PMID- 30202271
TI  - Assisting the Novice in Lifestyle Change.
AB  - The beginning of a lifestyle intervention is a sensitive time, as doing "too much
      too quickly" may stress the immune system, resulting in an increase in upper
      respiratory symptoms and, consequently, attrition. However, "too little too
      slowly" may not align with patients' motivation to change and may also result in
      attrition. There is also evidence that early weight loss is predictive of long
      term maintenance of goal weight. Health care providers are frequently presented
      with contradictory information on the best model to promote enduring lifestyle
      change. Best practice dictates that health care provider acknowledge their
      patients' motivation to change and incorporate each individual's goals in
      designing the lifestyle change intervention. Additional support and advice may be
      warranted at the beginning of an intervention to promote the patient's health and
      avoid attrition.

PMID- 30202268
TI  - Nutritional and Physical Activity Interventions to Improve Immunity.
AB  - Physical activity and nutrition are important in a healthy lifestyle with
      potential benefits to immunity often overlooked. Infection of the upper
      respiratory tract, and the associated symptoms, are the most frequent
      presentations to general practitioners and may have significant economic and
      social impact. In this review, we consider the role of physical activity and
      nutrition in improving immunity. Evidence suggests that regular moderate activity
      is particularly beneficial for immune enhancement and reducing the risk of
      infection. We also discuss some nutritional strategies. Unfortunately, the
      evidence for many is weak. Avoiding nutritional deficiencies seems the most
      pragmatic recommendation. This can be achieved with a balanced diet. Including a
      variety of fruits and vegetables may help ensure adequate intake of essential
      nutrients with little risk of excess intake of any single nutrient.
      Supplementation with individual nutrients is generally not recommended.
      Multinutrients may be beneficial for those with a preexisting deficiency but not
      if normal dietary intake is sufficient. Further benefit may be gained from some
      supplements including probiotics, bovine colostrum, and some plant-derived
      products (Echinacea, black elderberry, and some polyphenols) but only in specific
      situations/contexts. Individuals should consider their personal needs, use
      caution, and avoid the indiscriminate use of supplements.

PMID- 30202272
TI  - Vitamin C in the Prevention and Treatment of the Common Cold.
AB  - During the winter months, absenteeism or decreased productivity at work or school
      can often be attributed to symptoms of the common cold. Many people seek over-the
      counter (OTC) products for their symptoms, and some of the commonly purchased
      products are those with high-dose supplements of vitamin C (ascorbic acid). The
      common cold causes enormous morbidity worldwide, and it is important to know the
      effects of vitamin C for both preventive and therapeutic purposes to correctly
      recommend the proper OTC product for these symptoms. The purpose of this article
      is to review the current data on the relationship between vitamin C and immune
      function, specifically, the utility of vitamin C supplementation in the
      prevention and treatment of the common cold.

PMID- 30202273
TI  - Health Benefits of Exercise for People Living With HIV: A Review of the
      Literature.
AB  - With life expectancy increasing and the symptomatology of HIV being altered since
      the advent of antiretroviral therapy (ART), we now have begun to see metabolic
      changes with negative implications among people living with HIV/AIDS (PLWHA).
      Some of these changes include increased blood lipids, central fat accumulation,
      lipodystrophy, and decreased aerobic capacity. All of which are known risk
      factors for cardiovascular disease, cancer, and all-cause mortality. A common
      practice among healthy and other clinical populations to help modify these risk
      factors is some form of aerobic exercise, resistance exercise, or a combination
      of both. It has been demonstrated that PLWHA could respond in a similar manner,
      which in turn may enhance life expectancy and/or quality of life. The purpose of
      this literature review was to examine the evidence of health benefits of routine
      exercise training among PLWHA since the advent of ART. Although limited in
      strength because of small sample sizes and limited intervention durations, there
      is overall consistency in the general findings. An overview of the findings would
      indicate that physical activity and exercise are both safe and effective in
      improving cardiorespiratory fitness, metabolic profile, and quality of life among
      PLWHA.

PMID- 30202274
TI  - Act-Belong-Commit: Lifestyle Medicine for Keeping Mentally Healthy.
AB  - Lifestyle medicine has generally focused on behaviors related to improving
      physical health and preventing physical illnesses, with little attention to
      behaviors related to mental health. This reflects the far greater concern in
      health systems around the globe for physical health over mental health. The Act
      Belong-Commit campaign is the first major attempt to provide a lifestyle
      framework for promoting mental health that can be applied at a population level,
      within specific settings, and in the clinic. This article describes the campaign
      and offers clinicians a guide to implementing the campaign in their practice.

PMID- 30202275
TI  - Positive Psychology and Physical Health: Research and Applications.
AB  - Positive psychology is the scientific study of a healthy and flourishing life.
      The goal of positive psychology is to complement and extend the traditional
      problem-focused psychology that has proliferated in recent decades. Positive
      psychology is concerned with positive psychological states (eg, happiness),
      positive psychological traits (eg, talents, interests, strengths of character),
      positive relationships, and positive institutions. We describe evidences of how
      topics of positive psychology apply to physical health. Research has shown that
      psychological health assets (eg, positive emotions, life satisfaction, optimism,
      life purpose, social support) are prospectively associated with good health
      measured in a variety of ways. Not yet known is whether positive psychology
      interventions improve physical health. Future directions for the application of
      positive psychology to health are discussed. We conclude that the application of
      positive psychology to health is promising, although much work remains to be
      done.

PMID- 30202276
TI  - Motivators of and Barriers to Eating Foods and Snacks Among Adolescents.
AB  - Adolescents from low-income households and minority groups are disproportionately
      affected by obesity compared with their non-Hispanic white counterparts. Engaging
      in health promoting behaviors such as routinely eating healthy foods and snacks
      and engaging in physical activity are ways of preventing and reducing obesity and
      obesity disparities. The major purposes of the present study are (a) to identify
      the motivators of and barriers to eating healthy foods and snacks among
      culturally diverse adolescents and (b) to determine if the strengths of
      endorsement of these motivators and barriers differ by race, gender, and age. In
      the present study, a series of factor analyses was used to identify the
      motivators of and barriers to eating healthy foods and snacks among the
      culturally diverse adolescent participants (N = 172) in the national study.
      Specifically, an adolescent motivator of eating healthy foods and snacks scale,
      adolescent barrier to eating healthy foods and snacks scale, and subscales for
      each of these 2 scales were identified. The adolescent motivator subscales found
      were Knowledge and Commitment (alpha = .86) and Routine (alpha = .87). The
      adolescent barrier subscales found were Lack of Exposure (alpha = .72),
      Pessimistic Attitude (alpha = .80), and Temptation (alpha = .59). MANOVAs were
      used to determine if the mean scores for these scales and subscales differ by
      race, age, and gender. Nonsignificant differences were found among the mean
      scores for these scales and subscales. Results have implications for customizing
      adolescent health promotion interventions, including those to reduce and prevent
      obesity.

PMID- 30202277
TI  - Stress: A Core Lifestyle Issue.
AB  - Stress is a core issue to be addressed in lifestyle medicine. Not only does it
      influence disease directly (eg, cardiovascular disease), it also indirectly
      affects health by having a negative influence on other behaviors such as sleep
      and physical activity. The importance of stress is further highlighted by the
      fact that it is one of the most highly ranked health risks for employees
      globally. Practitioners are encouraged to attend to both significant life
      stressors and those that are encountered daily. Stress reduction strategies are
      further discussed.

PMID- 30202278
TI  - Influence of Sleep on Fertility in Women.
AB  - An estimated 15.5% of women in the United States experience infertility, and a
      wide range of conditions, behaviors, and exposures have been linked to this
      reduced reproductive capacity. Sleep is a critical component to health and well
      being, yet the amount of research devoted to determining the association between
      sleep and fertility in women is lacking. This article will discuss potential
      pathways by which sleep dysregulation may modulate fertility and summarize
      observational study data related to shift work and fertility.

PMID- 30202279
TI  - The Future of Health Promotion in the 21st Century: A Focus on the Working
      Population.
AB  - The purpose of this article is to synthesize developments from various
      disciplines including the medical, wellness, psychology, and sociology fields to
      shed light on where health promotion is headed in the next 25 years. Lifestyle
      medicine practitioners will continue to play a large role in helping people
      achieve the highest levels of wellness, which does not simply mean the absence of
      disease. New research identifies the important roles of many diverse factors such
      as relationships, lifestyle behaviors, emotional outlook, positive environment,
      mind-body connection, use of technology, and work styles, which can help each
      person achieve the fullness of life, vitality, and flourishing that characterizes
      a high level of well-being.

PMID- 30202280
TI  - The Impact of HPV as an Etiological Factor in Gynecological and Oropharyngeal
      Cancer.
AB  - The human papilloma virus (HPV) is one of several viral pathogens linked to human
      cancer. This article reviews the current worldwide cancer burden related to this
      pathogen. The article also examines the role of HPV in oropharyngeal and
      gynecological malignancies, current treatment implications, and future directions
      in the treatment and prevention of HPV-related disease.

PMID- 30202281
TI  - The Laughter Prescription: A Tool for Lifestyle Medicine.
AB  - Laughter is a normal and natural physiologic response to certain stimuli with
      widely acknowledged psychological benefits. However, current research is
      beginning to show that laughter may also have serious positive physiological
      effects for those who engage in it on a regular basis. Providers who prescribe
      laughter to their patients in a structured way may be able to use these natural,
      free, and easily distributable positive benefits. This article reviews the
      current medical understanding of laughter's physiologic effects and makes a
      recommendation for how physicians might best harness this natural modality for
      their patients.

PMID- 30202283
TI  - Back to Basics: Commonsense Approach to Optimizing Fecundity.

PMID- 30202284
TI  - Lifestyle Medicine: Continued Growth and Evolution.

PMID- 30202285
TI  - American College of Lifestyle Medicine Expert Panel Discussion: Lifestyle
      Medicine Integrating Evidence Into Practice 2015.

PMID- 30202282
TI  - Immune and Inflammatory Signaling Pathways in Exercise and Obesity.
AB  - Over the last decades the combination of both a sedentary lifestyle and excessive
      food availability has led to a significant increase in the prevalence of obesity,
      which is increasingly recognized as an important risk factor for type 2 diabetes.
      Several lines of evidence exist demonstrating that expanded visceral adipose
      tissue produces several pro-inflammatory mediators that activate signaling
      pathways that contribute to the development of insulin resistance. Exercise
      training is an important lifestyle factor that is widely used as a tool for
      preventing and improving lifestyle-related obesity and insulin resistance. In
      this regard, exercise training is useful to increase energy expenditure thereby
      counteracting a positive energy balance. Exercise training is also able to
      attenuate the activation of several obesity-induced pathways of inflammation and
      oxidative stress. Thus, a better understanding of the molecular mechanisms and
      immune pathways in exercise, obesity, and diabetes can be extremely useful to
      exploit optimized lifestyle strategies to combat the increasing incidence of
      metabolic diseases.

PMID- 30202286
TI  - Collaboration and Negotiation: The Key to Therapeutic Lifestyle Change.
AB  - Counseling patients on behavior change is an important skill that traditional
      medical training does not emphasize. Most practitioners are trained in the expert
      approach to handle problems, which is useful in the acute care setting. However,
      in the case of chronic disease, a coach approach is more effective. This approach
      allows the patient to reflect on his or her own motivators for change as well as
      obstacles hindering the change. Changing from the expert approach to the coach
      approach is contingent on the lifestyle medicine practitioner sharing information
      when the patient is ready to receive it, listening mindfully, asking open-ended
      questions, treating problems as opportunities to learn and grow, and encouraging
      patients to take responsibility for their actions. By collaborating with the
      patient, the practitioner can guide patients to find solutions to the problems
      they are facing and foster an environment that leads patients to self-discovery,
      accepting responsibility for their behaviors, and ultimately, achieving goals
      that result in healthier daily habits. As a framework and a guide, lifestyle
      medicine practitioners can use a 5-step cycle of collaboration and a ladder of
      behavior change when working with patients on behavior change.

PMID- 30202287
TI  - Defining an Overdue Requiem for Palliative Cardiovascular Medicine.
AB  - During the past 40 years, we have witnessed significant advances in the
      pharmaceutical and interventional treatment of cardiovascular disease (CVD),
      which have helped achieve a decrease in morbidity and mortality for this illness.
      Nevertheless, CVD remains the number 1 killer of women and men in Western
      civilizations. This fact is in stark contrast to the scenario in multiple whole
      food, plant-based nutrition (WFPBN) cultures, where CVD is virtually nonexistent.
      The utility of plant-based nutrition to halt and prevent CVD has been
      demonstrated epidemiologically, during wartime deprivation, in large cohort and
      population transitioning studies, and through prospective randomized and
      nonrandomized investigations. A basic scientific study confirms that omnivores
      have intestinal bacteria capable of converting animal food to trimethylamine
      oxide (TMAO), which injures blood vessels, whereas those eating plants only do
      not have intestinal bacteria capable of producing TMAO. Despite this overwhelming
      evidence for the safety, simplicity, and efficacy of plant nutrition to halt and
      prevent coronary artery disease, the cardiovascular medicine community has failed
      to embrace this option of therapy and persists in palliative treatments
      associated with high morbidity, mortality, and expense. It is long overdue to
      question why.

PMID- 30202288
TI  - Blue Zones: Lessons From the World's Longest Lived.
AB  - What began as a National Geographic expedition, lead by Dan Buettner, to uncover
      the secrets of longevity, evolved into the discovery of the 5 places around the
      world where people consistently live over 100 years old, dubbed the Blue Zones.
      Dan and his team of demographers, scientist and anthropologists were able to
      distill the evidence-based common denominators of these Blue Zones into 9
      commonalities that they call the Power 9. They have since taken these principles
      into communities across the United States working with policy makers, local
      businesses, schools and individuals to shape the environments of the Blue Zones
      Project Communities. What has been found is that putting the responsibility of
      curating a healthy environment on an individual does not work, but through policy
      and environmental changes the Blue Zones Project Communities have been able to
      increase life expectancy, reduce obesity and make the healthy choice the easy
      choice for millions of Americans.

PMID- 30202290
TI  - Leveraging Time With Lifestyle-Based Group Visits.
AB  - Many challenges in reversing the chronic disease epidemic boil down to a lack of
      available time. Without time, implementing effective lifestyle medicine therapies
      and creating a therapeutic partnership between provider and patient is
      ineffectual. Although useful, the individual medical appointment model alone has
      not proved to "bend the cost curve" or improve morbidity. Lifestyle-based group
      visits (LBGVs) are extended clinical encounters that allow physicians and their
      patients to exchange valuable information regarding optimal chronic disease
      management within a supportive group format. Clinically, LBGVs improve patient
      knowledge scores and chronic disease outcome measures. Operationally, they reduce
      lobby wait times, increase available new and established patient appointment
      slots (ie, improving access), and improve provider and patient satisfaction
      measures. LBGVs simultaneously improve patient lives, disease management costs,
      and practice revenue when used in primary care and specialty practices. By
      providing personalized lifestyle education coupled with in-depth behavior
      modification support from a provider and a peer group with similar successes and
      struggles, group visits reduce symptomatology and reverse disease progression
      without expensive medications, procedures, and technologies. Despite perceived
      obstacles, the group medical appointment model is easy to implement and provides
      consistent benefits in settings ranging from residency programs to cash-based
      boutique practices.

PMID- 30202289
TI  - Why We Don't "Just Do It": Understanding the Intention-Behavior Gap in Lifestyle
      Medicine.
AB  - Intention can be a poor predictor of actual health behavior change-now termed the
      intention-behavior gap. In other words, although patients intend to change and
      maintain their behavior, the data suggest that many will not follow through with
      their intention. This review introduces 5 factors that could help the
      practitioner understand the patient intention-behavior gap: (1) the motivation,
      (2) the trigger, (3) the response, (4) the capacity, and (4) the process. These
      key factors allow the lifestyle medicine practitioner to (1) understand the
      difficulties in changing patient behavior and (2) apply strategies to encourage
      successful change and maintenance of healthy lifestyle behavior in their
      patients.

PMID- 30202291
TI  - Interview With Award Winners From ACLM 2015, Nashville, Tennessee - John Kelly.

PMID- 30202292
TI  - Interview With Award Winners From ACLM 2015, Nashville, Tennessee - Dean Ornish.

PMID- 30202293
TI  - Lifestyle Medicine Practice: Exploring Workable Models.
AB  - The practice of lifestyle medicine is different than typical medical practices.
      Reimbursement systems are strong drivers of practice models. Lifestyle Medicine
      Solutions (LMS) has developed a primary care lifestyle medicine practice that
      implements: 1) a new clinical care model, and 2) innovative reimbursement
      strategies. The key assumptions, care model, reimbursement model and financial
      partners used by LMS are discussed. To achieve the promise that lifestyle
      medicine brings for decreasing both the chronic disease burden and rising health
      care costs, new lifestyle medicine delivery models must continue to be explored
      and implemented. The goal is for the lifestyle medicine choice to be available to
      each patient and each provider.

PMID- 30202294
TI  - Lifestyle, Lipids, and Cardiovascular Risk Reduction in a Woman With
      Metabolically Unhealthy Normal Weight.

PMID- 30202295
TI  - Theory-Based Interventions for Long-Term Adherence to Improvements in Diet
      Quality: An In-depth Review.
AB  - Many interventions aim to improve dietary patterns but not all are able to
      maintain these changes long term. Interventions informed by theory may facilitate
      dietary behavior changes and maintenance of these changes for longer periods of
      time. PubMed and PsychInfo were searched for theory-based interventions with long
      term assessments of fruit and vegetable (FV) and fat intake. We identified 335
      unique titles; 20 were included for review. Most interventions (65%) were based
      on social cognitive theory. Assessments of FV and fat ranged from 12 to 72 months
      postrandomization, and 15 studies reported significant intervention effects. Only
      6 studies directly tested theory in relation to diet and of those, significant
      findings indicated self-efficacy, motivation for dietary change, perceived
      competence to eat more FV and less fat, and multiple processes of change were
      associated with long-term maintenance of healthy eating. Overall, this review
      indicates that theory-informed interventions are generally successful for long
      term improvements in diet quality, although such improvements are often modest.
      Most studies did not directly measure theoretical constructs in relation to diet
      outcomes, thus limiting our ability to describe how theory-based interventions
      specifically promote long-term diet change. Recommendations for future research
      and practical recommendations for long-term maintenance of diet change are
      discussed.

PMID- 30202296
TI  - Theoretical, Critical, and Practical Reflections on the Long-Term Maintenance of
      Health Behavior Change.
AB  - This commentary is in response to Joseph, Daniel, Thind, Benitez and Pekmezi
      (2014). They reviewed randomized controlled trials (RCTs) that included long-term
      follow-up assessments at least 6 months post-intervention. Their main purpose was
      to understand which theory or model used by researchers could help explain the
      long-term maintenance of health behaviors once the intervention was withdrawn in
      trials focused on physical activity, dietary behavior, and excessive alcohol
      consumption. Results showed that social cognitive theory (SCT) and
      transtheoretical model (TTM) were used most often and associated with long-term
      behavior change compared to self-determination theory (SDT), theory of planned
      behavior (TPB), or the social-ecological model (SEM). SDT showed encouraging
      findings while the evidence was unclear for the TPB and the SEM. Here it is
      argued that scientists should continually reflect on the utility of theory over
      time and the efforts by Joseph and colleagues should be commended. It is also
      useful to distinguish theories, which are more specified and offer more
      generalized statements, than models. Models, such as the TPB and SEM, have
      incorporated elements of other theories but are typically viewed as tools to
      characterize behavior. For instance, in 10 studies reviewed by Joseph and
      colleagues the SCT and TTM were used in an integrative manner. An example of an
      integrated model is presented that incorporates elements of SDT, TPB, and SCT in
      an effort to highlight how integrating elements from multiple theories may be
      useful.

PMID- 30202297
TI  - Unidirectional or Bidirectional Relationships of Behaviors: The Importance of
      Positive Behavioral Momentum.
AB  - Theoretically based behavioral interventions provide the most evidence for
      successful change; however, several issues should be considered when applying
      these interventions. For example, school-based obesity prevention programs can be
      used to teach children how to adopt healthy lifestyle behaviors from an early
      age. Ecological systems theory provides a framework to design, implement, and
      evaluate school-based obesity prevention programs. An ecological framework
      emphasizes that the characteristics within and between systems place children at
      risk for obesity. Although this developmental process is considered to occur
      continuously and simultaneously, in practice, we tend to consider the
      relationships to be unidirectional. Using a positive behavioral momentum approach
      in practice may assist in addressing these complexities.

PMID- 30202298
TI  - Pharmacy Medication Synchronization Service Works to Improve Medication
      Adherence.
AB  - Medication adherence plays an important role in the effective management of
      chronic conditions, yet nonadherence related to therapeutic complexity and
      numerous visits to the pharmacy is well documented in the literature. Medication
      Synchronization (Med Sync) programs work to overcome this barrier by
      standardizing medication refills for a less frequent, generally once monthly
      pickup. Features of Med Sync programs as well the impact on adherence will be
      discussed.

PMID- 30202300
TI  - A Unique Lifestyle Medicine Model in the Sunshine State.

PMID- 30202299
TI  - Case Series in Lifestyle Medicine: A Team Approach to Behavior Changes.
AB  - As the number of people living with chronic diseases climbs upward, novel methods
      to address the root causes of these disease are necessary to transform the state
      of our nation's health and our health care system. Interventions directed at
      making lasting lifestyle changes can have a major impact on the overall health of
      patients. In this pilot study, 4 obese patients, with unhealthy habits and
      abnormal blood profiles and biometrics, were able to significantly improve their
      lifestyles and their lab values with the 3-month intervention of a lifestyle
      medicine team, including a physician trained in lifestyle medicine, a certified
      wellness coach, a licensed nutrition specialist, a physical therapist, and a
      licensed mental health professional. Two patients had type 2 diabetes, and all 4
      were hypertensive (blood pressure > 120/80 mm Hg). After the intervention, all
      improved their nutrition and increased their physical activity. In addition, all
      experienced improvements in lipid counts, blood pressure, weight loss, and
      cholesterol. The diabetic patients' levels of hemoglobin A1C dropped to normal.
      These successes show the benefits of a lifestyle medicine team approach.

PMID- 30202301
TI  - Optimizing Lifestyle Medicine Health Care Delivery Through Enhanced
      Interdisciplinary Education.
AB  - While few may argue about the importance of healthy lifestyle choices on the
      effects of chronic health conditions, many would highlight the challenge that its
      practical integration poses in daily clinical practice. The field of lifestyle
      medicine aims to assist individuals and communities to adopt and sustain healthy
      behaviors. It is a powerful yet often underutilized tool. This article
      illustrates the importance of joint multidisciplinary efforts in the effective
      practice of lifestyle medicine. Furthermore it stresses the importance of
      equipping healthcare providers with the tools and education necessary to deliver
      consistent, and high quality holistic care.

PMID- 30202303
TI  - Effects of Caffeine on Exercise Responses and Performance in Children and Youth.
AB  - Extensive research has been performed investigating the effects of caffeine
      during exercise in adults with many reviews published in just the past 10 years.
      Limited research has been conducted in children despite the fact that they are
      one of the fastest growing consumers of caffeine. In light of the limited
      research, in writing this review no inclusion or exclusion criteria were used, as
      the aim of the review is to provide as wide a research base as possible. This
      review will present the data that has systematically investigated the acute
      effects of caffeine in children and youth during exercise.

PMID- 30202304
TI  - College Students' Mobile Telephone Use Is Positively Associated With Sedentary
      Behavior.
AB  - While mobile phones (henceforth cell phones) provide nearly constant access to
      activities (eg, watching videos, playing games) traditionally associated with
      sedentary behavior, the relationship between cell phone use, sedentary behavior,
      and physical activity is untested. The purpose of this study was to assess these
      relationships. A sample of college students (N = 236) completed surveys assessing
      daily cell phone use, sedentary behavior (sitting time) and physical activity.
      Regression demonstrated that cell use was positively associated (beta = 0.23, P =
      .05) with sedentary behavior and not related (beta = -0.02, P = .90) to physical
      activity. Tertile splits were performed for average daily cell phone use and
      participants were grouped as high (n = 81), moderate (n = 77) or low (n = 78)
      cell users. High users (495.1 +/- 227.6 min/d) participated in significantly (P
      <= .03) more sedentary behavior than the moderate (417.1 +/- 208.3 min/day) and
      low (395.2 +/- 180.0 min/d) users. Sedentary behavior was not different (P = .5)
      between the moderate and low users. In conclusion, cell use was associated with
      college students' sedentary behavior but not physical activity. High users
      allocated 18.7% and 25.3% more time to daily sitting than moderate and low users,
      respectively.

PMID- 30202302
TI  - Lifestyle Approaches and Glucose Intolerance.
AB  - Glucose intolerance is a global health concern that encompasses glucose
      metabolism abnormalities such as impaired fasting glucose (IFG), impaired glucose
      tolerance (IGT), and type 2 diabetes (T2D). There is an urgent need to focus on
      the prediabetes (ie, IGT and IFG) stage before the disease actually occurs. The
      progression from IGT to T2D can be prevented or delayed by modifying the
      lifestyles in high-risk individuals, and these health benefits are well
      documented in various ethnicities with prediabetes across the world.
      Specifically, consuming a healthy diet (high in polyunsaturated fatty acids,
      monounsaturated fatty acids, fiber, and whole grains), losing weight, quitting
      smoking, consuming alcohol in moderation, and increasing physical activity can
      improve glucose tolerance and reduce the risk of T2D. Also, pharmacological
      agents and botanicals can be used to manage glucose intolerance if the
      implementation of lifestyle changes is challenging. Pharmacological treatments
      have been successful in managing glucose intolerance; however, they have adverse
      effects. Also, more research on botanicals is warranted before a definitive
      recommendation can be made for their use in managing glucose intolerance. To make
      progress on this worldwide problem, efforts are needed to improve the awareness
      of prediabetes, increase promotion of healthy behaviors, and improve the
      availability of evidence-based lifestyle intervention programs to the community.

PMID- 30202305
TI  - Diabetes Risk Assessment of the UC Irvine Campus Population.
AB  - Type 2 diabetes (T2D), historically affecting primarily older individuals, now
      affects younger people. Few studies have analyzed diabetes risk factors among
      younger individuals, including college students. We investigated risk in that
      overlooked population. A 2-part diabetes risk assessment survey was administered
      to University of California Irvine (UCI) students, faculty, and staff for 2
      months. Part I, including 26 questions, assessed participants' nutrition,
      physical activity, and stress management behaviors. Part II assessed risk
      according to American Diabetes Association (ADA) Risk Assessment's 8 demographic
      and lifestyle questions producing a risk score. Scores and behavioral factors
      analyzed risk on individual and community levels. Recruitment included emails and
      flyers promoting the UCI Electronic Educational Environment survey link.
      According to the ADA Risk Assessment scores of the 915 respondents, only 4% are
      at high risk of developing T2D. Although these scores indicate a small population
      at risk, our survey revealed a high prevalence of individuals practicing multiple
      unhealthy lifestyle behaviors associated with diabetes. These multiple behaviors
      may lead to high percentages of college students developing T2D, despite current
      low ADA risk status. We conclude the ADA Risk Assessment is geared toward an
      older demographic and may reflect short-term risk rather than longer-term risks.

PMID- 30202307
TI  - Individual and Environmental Barriers to Successful Aging: The Importance of
      Considering Environmental Supports.
AB  - The cornerstone to successful aging is maintaining a consistent physical activity
      routine and healthy diet. This is particular important for aging adults to
      preserve their independence. However, for low-income aging adults there are
      significant individual and environmental barriers that reduce their ability to
      maintain a healthy lifestyle. Understanding how environmental supports can be
      found in existing programs geared toward older adults is a way to insure long
      term behavioral changes.

PMID- 30202306
TI  - Attenuation of Adverse Effects of Aging on Skeletal Muscle by Regular Exercise
      and Nutritional Support.
AB  - Beginning early in midlife, natural/primary aging is inevitably associated with a
      progressive reduction in muscle mass and function. This process can progress with
      aging to a substantial loss of strength, particularly in the lower extremities,
      reducing mobility. This condition, commonly referred to as sarcopenia, can result
      in frailty, reducing one's ability to live independently. This article reviews
      the underlying biological process contributing to the development of sarcopenia
      and the roles of regular exercise and nutritional support for attenuating aging
      associated muscle loss as well as risk and management of sarcopenia and
      associated frailty.

PMID- 30202308
TI  - GERD Management: The Case for Lifestyle in an Era of PPIs.
AB  - Gastroesophageal reflux disease (GERD) is a common condition in the United
      States, routinely treated with proton pump inhibitors (PPIs). While effective and
      generally well tolerated, PPIs have been associated with undesirable long-term
      side effects and are often used inappropriately. Lifestyle medicine can be
      effective in reducing GERD symptoms in many patients without the untoward side
      effects of pharmacotherapy. This article will describe relevant emerging and
      established side effects of long-term PPI use, the efficacy of lifestyle
      modifications in the management of GERD, and discuss the importance of advocating
      for lifestyle when PPIs are not otherwise indicated.

PMID- 30202309
TI  - Lifestyle Approaches to White Coat Hypertension.
AB  - This case presentation illustrates the importance of 24 hour ambulatory blood
      pressure monitoring in patients with white coat hypertension, as many progress
      into sustained hypertension over time. Also, it serves as a reminder not to
      overlook a possible underlying sleep breathing disorder in patients who are not
      obese or fatigued. Finally, the case provides an opportunity to review the value
      of non-pharmacological and lifestyle approaches to the treatment of both white
      coat hypertension and sustained hypertension.

PMID- 30202310
TI  - Developing an Academic Lifestyle Medicine Clinic Model.
AB  - An introduction to lifestyle medicine as a patient, has led to the development of
      a lifestyle medicine program, website and practice. Having the advantage of
      practicing in an academic setting and a part time endoscopy practice has allowed
      for exploration and experimentation of different models of delivery of lifestyle
      medicine, the goal being to provide affordable accessible lifestyle medicine in a
      manner that is reproducible and sustainable for medical residents and students.

PMID- 30202311
TI  - Moving Toward a Better Balance: Stanford School of Medicine's Lifestyle Medicine
      Course Is Spearheading the Promotion of Health and Wellness in Medicine.
AB  - Stanford Medical School has created a class in lifestyle medicine that any
      student in the university can attend for credit. It is based on the foundational
      principles of lifestyle medicine and also informs students about topics such as
      Chinese medicine, naturopathic medicine, and wearable devices. The popularity of
      the course at Stanford speaks to the growing interest in the field of lifestyle
      medicine for medical students, undergraduate students, business students, and
      even engineers.

PMID- 30202312
TI  - On the Cusp.
AB  - A new president is stepping into leadership at the American College of Lifestyle
      Medicine (ACLM). Opportunities abound. The fact that both diabetes and heart
      disease are reversible is a message that is not reaching the majority of the
      general public. But times are changing and lifestyle treatment is on the cusp of
      being accepted as the self-evident best treatment for chronic medical conditions.
      ACLM is poised to be the leader in this area. Our members passion and experience
      are our richest resources. Each member is encouraged to be involved with the
      different committees of ACLM. Choices include Conference Planning, Education,
      Research, practice Models, Publications, Awards, Business Development, Membership
      Development, Strategic Partnerships, Marketing and Communications.

PMID- 30202314
TI  - Diabetes and Sports: Managing Your Athlete With Type 1 Diabetes.
AB  - More than 29 million people in the United States have diabetes mellitus,
      including both type 1 and type 2 diabetes. The CDC also estimates that upward of
      86 million people can be classified as prediabetic, with as many as 30% of these
      people transitioning into diabetes within the next 5 years. Individuals with type
      1 diabetes account for roughly 5% of those patients. Dating back to 2008 and
      2009, roughly 18 000 youth were diagnosed with type 1 diabetes each year. The
      prevalence of diabetes is well known; most of the studies that are completed
      today relate to the progression and/or treatment of those with type 2 diabetes.
      Yet most physicians will have to take care of a type 1 diabetic patient who will
      want to be active. Having a fundamental knowledge of how exercise affects insulin
      and blood glucose and how to manage these patients is important. Time must be
      taken to modify each treatment regimen for each individual. One cannot stress
      enough the importance of providing patient education, ensuring adequate
      hydration, recognizing signs and symptoms of hypoglycemia/hyperglycemia, and how
      to treat and prevent these serious complications. All patients must have a care
      plan and access to supplies during exercise. It is known that poorly controlled
      blood glucose can have detrimental consequences in the long term. The question is
      if type I diabetic athletes who are allowed to have higher blood glucose during
      exercise are at the same risk for these potential complications.

PMID- 30202316
TI  - Integrating Mobile Fitness Trackers Into the Practice of Medicine.
AB  - Mobile fitness trackers are increasingly used by patients as a means to become
      more involved in their own self-care; however, these devices measure disparate
      outcomes that may have equivocal relevance to true health status. It is vital for
      physicians to interpret both the quality and accuracy of the information that
      these trackers provide, and it is important to delineate which role, if any,
      these devices may serve in promoting quality patient care in the future.
      Potential benefits of mobile fitness trackers include the ability to motivate
      patients toward a healthier lifestyle, to develop a community of like-minded
      individuals seeking to improve their health, as well as to create an environment
      of sustainability and accountability for long-term promotion of health
      maintenance. However, limitations include the fact that mobile fitness trackers
      are not regulated by the Food and Drug Administration, that the employed metrics
      are not necessarily the best surrogates for true health status, and that the
      accuracy of measured endpoints has not yet been proven. As mobile fitness
      trackers both continue to rise in popularity and become increasingly
      sophisticated, physicians must be equipped to interpret and use this technology
      to better serve patients within an ever-changing, more technology-reliant health
      care system.

PMID- 30202317
TI  - Closing America's Fiber Intake Gap: Communication Strategies From a Food and
      Fiber Summit.
AB  - Adequate intake of dietary fiber is associated with digestive health and reduced
      risk for heart disease, stroke, hypertension, certain gastrointestinal disorders,
      obesity, type 2 diabetes, and certain cancers. According to consumer research,
      the public is aware of the benefits of fiber and most people believe they consume
      enough fiber. However, national consumption surveys indicate that only about 5%
      of the population meets recommendations, and inadequate intakes have been called
      a public health concern. To address the fiber consumption gap and formulate
      potential solutions, researchers, educators, and communicators convened at a Food
      & Fiber Summit on January 28, 2014, in Washington, DC. Panelists and attendees
      devised communication strategies to correct consumer misperceptions about fiber.
      These misperceptions include commonly held beliefs that all whole-grain foods are
      good sources of fiber and that foods with fiber are expensive, unpalatable, and
      complicated to prepare. To help close the fiber intake gap, nutrition and health
      educators can use communication strategies such as providing clear and concise
      information, recommending flavorful fiber-rich foods, and describing the benefits
      of adequate fiber intake. Several supporting messages were developed to
      effectively communicate about fiber. An example is to advise people to
      consistently check nutrition labels to find good sources of fiber.

PMID- 30202313
TI  - State of the Art Review: Physical Activity and Older Adults.
AB  - Physical activity is an important component of a healthy lifestyle for all adults
      and especially for older adults. Using information from the updated 2008 Physical
      Activity Guidelines, 3 dimensions of physical activity are identified for older
      adults. These include increasing aerobic activity, increasing muscle
      strengthening activity, and reducing sedentary or sitting behavior. Although the
      overall goal of the physical activity recommendations is to prevent chronic
      diseases and conditions from developing, many older adults are already affected.
      Therefore, suggested types of physical activity are described for specific
      diseases and conditions that are designed to mediate the condition or prevent
      additional disability. Finally, barriers to participation in physical activity
      specific to older adults are described, and possible solutions offered.
      Encouraging older adults to continue or even start a physical activity program
      can result in major health benefits for these individuals.

PMID- 30202315
TI  - Aquatic High Intensity Interval Training for Cardiometabolic Health: Benefits and
      Training Design.
AB  - High-intensity interval training (HIIT) has emerged as an attractive alternative
      to traditional continuous exercise training (CT) programs for clinical and
      healthy populations who find that they can achieve equal or greater fitness
      benefits in less time. Land-based HIIT may not be an appropriate choice for some
      participants. Few studies have explored the acute responses and chronic
      adaptations of HIIT in an aquatic environment, and no study has compared the
      cardiometabolic responses of an aquatic-based program to a land-based HIIT
      program. Shallow-water aquatic exercise (AE) programs utilizing HIIT have
      elicited comparable and, in some cases, greater physiological responses compared
      with constant-intensity or continuous AE regimens. Factors that may explain why
      HIIT routines evoke greater cardiometabolic responses than CT protocols may be
      based on the types of exercises and how they are cued to effectively manipulate
      hydrodynamic properties for greater intensities. Favorable aquatic HIIT protocols
      such as the S.W.E.A.T. system may serve as a beneficial alternative to land-based
      HIIT programs for clinical, and athletic populations, potentially reducing the
      likelihood of associated musculoskeletal and orthopedic complications. Hence, the
      purpose of this review is to examine the role of AE as an alternative safe and
      effective HIIT modality.

PMID- 30202318
TI  - The Importance of Dog Ownership: Implications for Long-Term Weight Reduction
      After Gastric Banding.
AB  - Gastric banding (GB) is considered an option to support weight loss for
      individuals who are unable to lose weight through diet and exercise alone.
      Exercise is an important element of maintaining gradual weight loss following GB.
      Dog walking may be one method to encourage exercise and contribute to continued
      weight loss. Over a 5-year period, 24 individuals aged between 31 and 58 years
      (21 female; 12 dog-owners) were weighed at 7 time points. Intention to treat
      MANOVA analysis showed both groups lost a significant amount of weight, F(6, 17)
      = 15.7, P = .001, etap2 = .85, but no difference was observed between dog owners
      and non-dog owners, F(6, 17) = 0.66, P = .68, etap2 = .19, although from 24
      months postbanding, data indicated dog owners appear to weigh less than non-dog
      owners. Further longitudinal research is warranted beyond 5 year post-GB; and
      encouraging exercise through dog walking may be a useful adjunct to increasing
      activity and promoting weight loss following GB.

PMID- 30202320
TI  - Vigorous Physical Activity in Youth: Just One End of the Physical Activity
      Spectrum for Affecting Health?
AB  - This article provides commentary on the accompanying manuscript entitled "The
      Case for Vigorous Physical Activity in Youth" by Owens and colleagues. A major
      strength of the review was its aim to determine whether vigorous physical
      activity provides greater benefits with respect to several health outcomes among
      children and youth while also considering the limitations of the current evidence
      in terms of number of studies and study design. This commentary presents
      additional topics to consider, practical applications, and conclusions and
      recommendations that can be drawn from the current evidence. To expand "the case
      for vigorous physical activity in youth," future studies should consider
      delineating the relative benefits of vigorous physical activity compared not only
      with moderate physical activity, but also with light and total activity.

PMID- 30202319
TI  - The Case for Vigorous Physical Activity in Youth.
AB  - Although it is widely recognized that regular physical activity is associated
      with a variety of health-related benefits in youths, the extent to which vigorous
      physical activity, as opposed to moderate or light physical activity, may be
      especially beneficial for youths is not completely understood. This review will
      examine the evidence for the efficacy of vigorous physical activity for promoting
      the well-being of youths as indicated by body composition, physical fitness,
      cardiometabolic biomarkers, and cognitive function. Potential caveats associated
      with the promotion of vigorous physical activity among youths will also be
      discussed, as will the inclusion of vigorous physical activity in current
      recommendations by national organizations for physical activity among youths.

PMID- 30202321
TI  - The Issue of Aversion in Lifestyle Treatments.
AB  - Increasing evidence suggests that vigorous physical activity (PA) is more
      beneficial than moderate PA for reducing adiposity and improving bone health in
      youth. However, beginning a vigorous PA program is not an easy behavior
      adjustment and the change is likely to be aversive for some individuals. In order
      to benefit from vigorous PA, health care providers need to help individuals
      increase self-efficacy.

PMID- 30202322
TI  - Performance-Enhancing Drug Use in Adolescence.
AB  - Despite inconclusive efficacy data and concerning safety data, the use of
      performance-enhancing drugs (PEDs) in the adolescent population is on the rise.
      Anabolic-androgenic steroids, growth hormones, stimulants, and erythropoiesis
      stimulating agents are among the most widely known and studied prescription PEDs
      in the adolescent population. The purpose of this article is to describe the
      proposed mechanism of action, efficacy and adverse effects of these agents as
      well as discuss prevention measures and treatment considerations for those
      patients at risk for, considering, or currently using PEDs.

PMID- 30202324
TI  - Lifestyle Medicine in an Academic/Hospital Context.
AB  - The effective integration of lifestyle medicine into allopathic practices is an
      evolving necessity driven by limited resources and escalating costs. Efforts in
      the Florida Hospital system graduate medical education (GME) department to meet
      this challenge may be instructive to others. Efforts include the hiring of an
      experienced dietician with a focus on a whole food plant based diet and a patient
      engagement tool to identify areas where patients are ready to make change.
      Billing is done using existing finance structure with the goal of decreasing the
      overall cost of providing care within a Clinically Integrated Network (CIN)
      context. Additionally, one GME clinician's experience in clinical lifestyle based
      intervention identifies and comments on several practical clinical factors for
      bringing effective behavior change to individual patients: patient readiness, a
      knowledgeable health care provider, adequate time, as well as the effectiveness
      of the intervention.

PMID- 30202325
TI  - NextGenU.org's Free, Globally Available Online Training in Lifestyle Medicine.
AB  - NextGenU.org now uniquely offers a free, accredited, globally-available online
      training in Lifestyle Medicine. Courses such as Lifestyle Medicine for Primary
      Care Physicians, Prevention and Treatment of Alcohol Use Disorders/Tobacco Use,
      Substance Use Disorder Screening, Public Health Nutrition, and more are
      competency-based and include knowledge transfer, a web-based global peer
      community of practice, and local, skills-based mentorships. Trainings use
      existing, expert-created resources from governments, universities, and medical
      specialty societies thus ensuring their quality and simultaneously making them
      free of costs, advertisement, and geographic barriers. To offer free credits for
      these courses, NextGenU.org partners with universities and professional
      societies. NextGenU.org's comprehensive Lifestyle Medicine Curriculum will launch
      in early 2017.

PMID- 30202326
TI  - Lifestyle Medicine: Making the Choices Clear?
AB  - Patients are often not aware of the reversibility of chronic lifestyle-related
      diseases and most physicians are not telling them. The present practice of
      communicating treatment effectiveness with relative risk reductions does not
      allow clinicians or patients to evaluate the relative effectiveness of our
      technotherapies or lifestyle interventions. Clinicians should use the clarity of
      "number needed to treat," "number needed to harm," and absolute risk in
      communicating with patients about all available therapies and then empower the
      patient to make the choices that fit their needs best.

PMID- 30202323
TI  - Postmenopausal Osteoporosis: The Role of Lifestyle in Maintaining Bone Mass and
      Reducing Fracture Risk.
AB  - Postmenopausal osteoporosis is a significant contributor to morbidity and
      mortality. Medications can provide effective treatment but their use can be
      complicated by side effects. This case illustrates the role that diet,
      supplements, and specific exercises can play in preventing and treating bone loss
      and reducing fracture risk.

PMID- 30202328
TI  - Clinical Effectiveness of Lifestyle Health Coaching: Case Study of an Evidence
      Based Program.
AB  - We have developed, tested, and successfully implemented an affordable, evidence
      based, technology-enabled, data-driven, outcomes-oriented, comprehensive
      lifestyle health coaching (LHC) program. The LHC program has been used primarily
      to provide services to employees of larger employers (ie, with at least 3000
      employees) but has also been implemented in a variety of other settings,
      including hospitals, cardiac rehabilitation centers, physician practices, and as
      part of multicenter clinical trials. The program is delivered mainly using the
      telephone and Internet. Health coaches are guided by a Web-based participant
      management and tracking system. Lifestyle management interventions are based on
      several behavior change models and strategies, especially adult learning theory,
      social learning theory, the stages of change model, single concept learning
      theory, and motivational interviewing. The program is administered by
      nonphysician health professionals whose services are integrated with the care
      provided by participants' physicians. Outcomes data from published studies,
      including randomized clinical trials and independent third-party conducted
      research, have documented the clinical effectiveness of this evidence-based
      approach in terms of modification of multiple risk factors in healthy persons as
      well as those with certain common chronic diseases.

PMID- 30202327
TI  - Lifestyle Modification in Secondary Prevention: Beyond Pharmacotherapy.
AB  - Despite significant advances in medical technology and pharmacology,
      cardiovascular disease (CVD) remains a major contributor to health care expenses
      and the leading cause of death in the United States. Patients with established
      CVD and their health care providers are challenged with achieving cardiovascular
      risk reduction to decrease the likelihood of recurrent cardiovascular events.
      This "secondary prevention" can be achieved, in part, through adherence to
      prescribed pharmacotherapies that favorably modify major coronary risk factors
      (ie, hypertension, hypercholesterolemia, diabetes, and obesity). However,
      lifestyle modification can also be helpful in this regard, providing independent
      and additive benefits to the associated reductions in cardiovascular morbidity
      and mortality. Accordingly, physicians and other health care providers should
      routinely counsel their coronary patients to engage in structured exercise and
      increased lifestyle physical activity, consume a heart-healthy diet, quit smoking
      and avoid secondhand smoke, and purposefully address psychosocial stressors that
      may elevate cardiovascular risk. These lifestyle interventions, either as an
      adjunct to medication therapy or independently in those patients where
      medications may be poorly tolerated, cost prohibitive, or ineffective, can
      significantly decrease cardiovascular mortality and the risk of recurrent cardiac
      events.

PMID- 30202330
TI  - Skin Cancer Risk and Other Health Risk Behaviors: A Scoping Review.
AB  - Purpose. To present results of a scoping review focused on skin cancer risk
      behaviors and other related health risk behaviors. Skin cancer is highly
      preventable, yet it is the most common form of cancer in the United States with
      melanoma rates increasing. Limited research has been conducted examining the
      relationship between skin cancer prevention behaviors and other health risks, yet
      multiple behavioral health risk interventions have shown great promise for health
      promotion and reduced health care costs. Methods. Online databases were searched
      for research articles on skin cancer risk behaviors and related health risk
      behaviors. Results. Thirty-seven articles met inclusion criteria examining skin
      cancer behaviors including risk, sun protection behaviors, sunburn, and indoor
      tanning. The majority of existing studies focused on the relationship between
      skin cancer prevention behaviors and physical activity, body mass index, smoking,
      and alcohol abuse. Adults were the primary population of interest with some
      studies of adolescents. Conclusions. Poor skin cancer prevention behaviors were
      associated with alcohol use, marijuana use, and smoking among adolescents and
      adults. Studies on body mass index and physical activity had mixed relationships
      with skin cancer prevention behaviors and warrant further investigation. Indoor
      tanning was associated with other risky behaviors but other skin cancer
      prevention behaviors were not studied.

PMID- 30202331
TI  - Paternal Mental Health: Why Is It Relevant?
AB  - Father's mental health is an emerging area of interest that is beginning to be
      recognized in research, and to a lesser extent in clinical practice and society.
      Fathers are part of a parenting dyad with 2 partners who are responsible for
      their children's emotional development. Similar to mothers, the risk for mental
      health problems increases once a male becomes a father, but there is limited
      research examining this issue. The purpose of this review is to present the
      available literature on father's mental health and its effect on child emotional
      health through various mechanisms. In general, father's mental health was found
      to be related to increased child internalizing and externalizing behaviors, but
      each disorder had different risk factors, and a unique effect on parenting
      behaviors and the child's emotional health. The most developed paternal mental
      health literature is focused on depression. However, key conceptual and
      methodological problems exist that may limit our understanding of paternal
      depression. Additionally, the focus on paternal depression may not accurately
      represent the largest risk for paternal psychopathology and the resultant child
      mental health outcomes because men have an increased likelihood of displaying
      externalizing behaviors. Implications for research, clinical practice, and policy
      are discussed.

PMID- 30202332
TI  - Paternal Physical Activity: An Important Target to Improve the Health of Fathers
      and their Children.
AB  - Although the transition to fatherhood is joyful and fulfilling for many men,
      becoming a father also exposes men to a series of new challenges and
      responsibilities that can negatively affect their well-being. As such, effective
      strategies that foster positive physical and mental health in fathers are
      required. Given the established links between regular physical activity and
      optimal health, strategies to reduce the substantial decline in physical activity
      typically observed during the early fatherhood may be particularly fruitful. In
      this commentary, we discuss the potential mediating role of physical activity on
      a series of important outcomes for fathers, including paternal and child health
      and the quality of the father-child relationship. We also present an argument
      that high-quality research studies testing physical activity interventions that
      meaningfully engage fathers are urgently required.

PMID- 30202334
TI  - When Is Pharmacotherapy Initiation Beneficial in Patients With Depressive
      Disorders?
AB  - Psychotherapy and pharmacotherapy are the most common treatments utilized in
      patients diagnosed with depressive disorders. Their efficacy in remitting
      symptoms and restoring patients to baseline functioning has been established
      throughout the literature; however, questions still remain on whether
      pharmacotherapy is necessary in all patients and if used, when initiation is most
      beneficial. Current guidelines recommend initiating only psychotherapy in
      patients with mild depression and advancing to pharmacotherapy as appropriate.
      Evidence-based literature has shown pharmacotherapy to have a significant and
      independent treatment effect in depressive disorders compared with psychotherapy.
      Combination treatment with both modalities has also shown to be beneficial for
      remitting depressive symptoms in this patient population. Therefore, treatment
      should be individualized for each specific patient based on severity of disease,
      history of depression and response to treatment, cost of treatment, and patient
      preference.

PMID- 30202329
TI  - The Current Understanding of Sarcopenia: Emerging Tools and Interventional
      Possibilities.
AB  - The purpose of this review is to provide health practitioners and physicians the
      most current state of the research on sarcopenia, its consequences, and to offer
      a summary of consensus guidelines for identification based on the most recent and
      compelling investigations and analyses. To accomplish this, the causes and
      consequences of sarcopenia will be described, and definitions and screening
      methods are updated. Importantly, interventional recommendations for sarcopenia
      will be discussed with a special emphasis on the effects of resistance training
      on sarcopenia-related outcomes. Furthermore, due to the increasing usage of
      hormone treatment as a strategy to combat sarcopenia, special consideration on
      the effects of hormone changes with aging and as interventions will be briefly
      reviewed.

PMID- 30202333
TI  - Engaging Fathers in the Promotion of Healthy Lifestyle Behaviors.
AB  - Parental engagement is an important component in lifestyle behavior change
      interventions for children as parents are uniquely positioned to establish a
      healthy environment and model healthy eating and physical activity habits for
      their children. Despite both mothers and fathers being important agents of
      behavioral change for their children, fathers are typically underrepresented in
      programming interventions. Physical activity may be an important strategy for
      fathers to become involved in lifestyle change with their children as, compared
      to mothers, fathers traditionally tend to be comfortable engaging in physical
      activity with their children.

PMID- 30202335
TI  - No More Pain in the Gut: Lifestyle Medicine Approach to Irritable Bowel Syndrome.
AB  - Irritable bowel syndrome has often underestimated negative impact of quality of
      life. Traditional symptomatic treatment does not address underlying complex
      etiology. Superior results might be achieved with combination of lifestyle
      medicine, correction of underlying microbial imbalances and retraining of
      autonomic nervous system as demonstrated in this case presentation.

PMID- 30202336
TI  - Applying the Business of Lifestyle Medicine.
AB  - Lifestyle medicine improves health outcomes by educating and equipping evidence
      based interventions to treat and prevent non-communicable disease. The Business
      of Lifestyle Medicine offers tools and a framework that enables organizations,
      corporations, healthcare systems, and providers to operationalize the practice of
      Lifestyle Medicine. The Business of Lifestyle Medicine is the application of an
      intensive induction phase, followed by tapered consolidation and ongoing
      sustainability utilizing risk stratification and often demonstrating cost
      savings. The purpose of this article was to outline some of my experiences with
      the Business of Lifestyle Medicine, highlight pivotal considerations when
      creating a Lifestyle Medicine practice, and illustrate a Lifestyle as Medicine
      Business Model.

PMID- 30202337
TI  - The American Board of Lifestyle Medicine.

PMID- 30202339
TI  - Rock Climbing for Promoting Physical Activity in Youth.
AB  - Prevalence of overweight and obesity in youth has steadily increased over the
      last decade, although it appears to have currently stabilized. Physical
      inactivity is a major contributor to this obesity epidemic, and more than half of
      American youth do not meet physical activity recommendations. Rock climbing and
      bouldering require both aerobic and anaerobic fitness, with the metabolic cost
      comparable to moderate to vigorous physical activity in adults. Minimal data on
      youth climbers exist, yet climbing is extremely popular with youth, and thus the
      sport may be a viable option for decreasing the prevalence of obesity. Available
      data show that rock climbing can provide youth with muscular strength and
      endurance building exercise, and possibly improve flexibility. In addition, rock
      climbing has the potential to provide youth with moderate levels of physical
      activity according to recommended guidelines. Nine peer reviewed articles are
      included in this review, as these are the articles specifically associated with
      youth climbing and health-related fitness. Due to limited research in this area,
      no articles were excluded if they were related to health-related fitness and
      youth and rock climbing/bouldering. This review aims to systematically address
      the impact of rock climbing and bouldering on health-related fitness in youth.

PMID- 30202340
TI  - Body Image, Weight, and Self-Concept in Men.
AB  - In the traditional debate between biological and environmental determinants of
      body weight, the body has most often been explored in terms of its anatomical,
      genetic, or hormonal influences on personality, experience, and behavior. While
      obesity has been identified as a threat to our public health, correlating
      attitudes toward body image and self-concept have been explored within women to a
      limited extent, and even less so in relation to men. Consequently, men's body
      image will be discussed in light of current literature reveals for women. For
      men, as for women, as the social pressure to attain an "ideal" physique
      increases, the discrepancy between that ideal and one's body increases as well.
      This dynamic is more readily recognized for women than for men. As men are
      socialized not to discuss their body image concerns, negative self-concept and
      esteem may reinforce behaviors resulting in weight gain. In recent years, the
      proliferation of media has served to reinforce messaging related to one's body.
      This review of existing data and literature suggests that body image and self
      concept are related to body weight in men (as with women) and need to be
      addressed as part of healthy weight management practices.

PMID- 30202338
TI  - A Review of the Promotion of Fitness Measures and Health Outcomes in Youth.
AB  - The relationship between physical fitness and health in adults is well
      established, yet until recently, empirical support for the impact of physical
      fitness levels on health markers in children has not been thoroughly documented.
      The aim of this review was to provide a summary of current literature that has
      examined the linkage between measures of health-related physical fitness (ie,
      cardiorespiratory fitness, musculoskeletal fitness, flexibility, and body
      composition) and health markers in youth. Specifically, this review focused on
      the findings from the recent 2012 Institutes of Medicine report on Fitness
      Measures in Youth as well as other subsequent review articles related to the
      topic. In addition, recommendations for health-related fitness assessments in
      youth populations are presented.

PMID- 30202341
TI  - Rare-Earth Magnet Ingestion-Related Injuries in the Pediatric Population: A
      Review.
AB  - Foreign-body ingestions are common among children and usually resolve with
      limited, if any, treatment. The ingestion of rare-earth magnets, however,
      commonly results in serious injury or death. These dangerous high-powered magnets
      can be found in the United States in a variety of consumer products, including
      magnetic toy sets designed for children and adults. The ingestion of one of such
      magnet is unlikely to cause significant harm. However, if multiple magnets are
      ingested, or if a magnet is ingested along with a metal object, the magnets are
      powerful enough to attract each other through the walls of the intestine,
      potentially resulting in significant internal damage. Rare-earth magnet ingestion
      cases are difficult to diagnose and the symptoms are not easy to differentiate
      from other causes of gastrointestinal illness or pain. However, delays in medical
      treatment can lead to serious injury or death. This review article describes the
      epidemiology of rare-earth magnet ingestion-related injuries and provides
      recommendations for diagnosis and treatment. Federal regulatory efforts related
      to rare-earth magnets and other prevention strategies are also discussed.

PMID- 30202342
TI  - Improved Cardiovascular Parameter With a Nutrient-Dense, Plant-Rich Diet-Style: A
      Patient Survey With Illustrative Cases.
AB  - Background. The results presented from a practice survey include cases of
      interest, demonstrating improvements in cardiometabolic risk factors utilizing a
      Nutrient-Dense, Plant-Rich (NDPR) diet. It includes changes in weight, blood
      pressure, and lipids parameters derived from the survey and retrospective chart
      review. Methods. Practice records and interviews were used for case history
      descriptions. Participants' data were collected via an online survey. Results.
      Adherence to a NDPR dietary protocol resulted in reduced low-density lipoprotein
      cholesterol and serum triglycerides. Compliance of greater than 80% with the
      target diet resulted in an average sustained weight loss of over 50 pounds in 75
      obese subjects. There was a corresponding average reduction of 27.8 mm Hg in
      systolic blood pressure for the 127 survey responders with untreated hypertension
      at baseline, and a 42.2 mg/dL average decrease in low-density lipoprotein
      cholesterol for the 328 survey responders, not on cholesterol reducing
      medications. Conclusion. The outcomes from both the survey responders and cases
      demonstrate the potential for the NDPR dietary intervention to improve weight,
      blood pressure, lipids, and even reverse severe cardiovascular disease. Though
      this is a report of cases and self-reported benefits, it adds evidence to support
      the need for further studies investigating the potential of this dietary
      intervention.

PMID- 30202343
TI  - Optimizing the Intensity of Lifestyle Medicine Interventions: Similar Outcomes
      for Half the Sessions.
AB  - Lifestyle medicine interventions are typically intensive by design. This study
      explored the optimal "dosage" of a well-known lifestyle medicine intervention-the
      Complete Health Improvement Program (CHIP). A total of 2383 individuals (mean age
      = 61.0 +/- 9.2 years; 34% males) participated in either an 8-session (N = 448) or
      16-session (N = 1935) version of the CHIP intervention conducted over 4 weeks in
      community settings throughout North America. Both the 8- and 16-session groups
      experienced significant improvements in all the chronic disease risk factors
      measured. There was no difference between the changes experienced by the 8- and
      16-session groups in lipid profile, fasting plasma glucose, or systolic blood
      pressure. The 8-session group experienced a significantly greater reduction in
      body mass (0.3 percentage points or 0.8 lbs, P < .01), but the 16-session group
      recorded a significantly greater reduction in diastolic blood pressure (2.8
      percentage points or 2.2 mm Hg, P < .01). There was no clear difference between
      the outcomes achieved in 4 weeks by the 8- and 16-session versions of the CHIP
      lifestyle medicine intervention. This study suggests that the short-term outcomes
      achieved by a 16-session CHIP intervention can be achieved in half the number of
      sessions, which has implications from a resourcing and cost-effectiveness
      perspective.

PMID- 30202346
TI  - Physical Inactivity, Self-Management, and Living Well With COPD.
AB  - Physical inactivity is an underrecognized and undertreated lifestyle behavior
      among patients with chronic obstructive pulmonary disease and is independently
      associated with a number of adverse health-related outcomes. Pulmonary
      rehabilitation with exercise training provides an efficacious intervention with
      short-term improvements, but it is an infrequently used modality and does not
      consistently result in longer term increases in physical activity. Similarly,
      pedometer self-monitoring with coaching has demonstrated short-term increases in
      physical activity. However, further research is needed to determine the optimal
      method to support long-term behavior change that will have the greatest benefit.
      While available evidence suggests that reversing physical inactivity is an
      essential component of self-management to optimize health, it is only one
      component of a complex set of interventions needed to support patients in
      adapting to their chronic condition. In the future, this support will ideally
      start with identification of specific patient phenotypes, which describes their
      adaptation to the condition based on patients' knowledge, skills, confidence,
      symptoms, and impairments. This information will then be used to tailor education
      and behavior change strategies over the long term to promote sustainable physical
      activity and other healthy lifestyles.

PMID- 30202344
TI  - Indoor Air Quality.
AB  - Many health care providers are concerned with the role environmental exposures
      play in the development of respiratory disease. While most individuals understand
      that outdoor air quality is important to their health status, many are unaware of
      the detrimental effects indoor air pollution can potentially have on them. The
      Environmental Protection Agency (EPA) regulates both outdoor and indoor air
      quality. According to the EPA, indoor levels of pollutants may be up to 100 times
      higher than outdoor pollutant levels and have been ranked among the top 5
      environmental risks to the public. There has been a strong correlation between
      air quality and health, which is why it is crucial to obtain a complete
      environmental exposure history from a patient. This article focuses on the
      effects indoor air quality has on the respiratory system. Specifically, this
      article will address secondhand smoke, radon, carbon monoxide, nitrogen dioxide,
      formaldehyde, house cleaning agents, indoor mold, animal dander, and dust mites.
      These are common agents that may lead to hazardous exposures among individuals
      living in the United States. It is important for health care providers to be
      educated on the potential risks of indoor air pollution and the effects it may
      have on patient outcomes. Health problems resulting from poor indoor air quality
      are not easily recognized and may affect a patient's health years after the onset
      of exposure.

PMID- 30202345
TI  - Chronic Obstructive Pulmonary Disease.
AB  - COPD is a common, preventable, and treatable disease characterized by persistent
      airflow obstruction associated with enhanced inflammation in the airways and the
      lung in response to noxious particles or gases. Clinical history and pulmonary
      function testing are necessary for accurate diagnosis. While exposure to tobacco
      smoke remains a common cause, other etiologies and underlying genetic
      predisposition play significant roles. Treatment options are numerous and should
      be individualized based on symptoms and exacerbation frequency.

PMID- 30202347
TI  - Reducing Anxiety to Increase Exercise in Individuals With Decreased Lung
      Capacity.
AB  - The management of chronic disease is complex. For many diseases, the treatment
      for the disease may mimic disease symptoms. For example, exercise training is
      recommended as part of the treatment of chronic obstructive pulmonary disease
      (COPD). Individuals may confuse the physiological experiences related to exercise
      with COPD symptoms. This type of association between treatment and disease can
      cause anxiety. For health care practitioners to successfully motivate their
      patients to make the necessary behavior changes for disease treatment, anxiety
      must also be addressed.

PMID- 30202348
TI  - Immunotherapy for Cat Allergies: A Potential Strategy to Scratch Back.
AB  - Cat allergies are a common and costly problem in the United States. Various drug
      and nondrug therapies exist to alleviate and control symptoms once allergic
      disease has developed. However, these therapies are often ineffective or do not
      address the underlying condition itself. Immunotherapy is an option for patients
      when symptoms are not adequately controlled by medications and/or avoidance
      measures, when adverse effects of medications are unacceptable, or when the
      patient wants to reduce their long-term use of medication. The purpose of this
      article is to describe the efficacy and safety of immunotherapy when used to
      prevent or treat cat allergies.

PMID- 30202350
TI  - Navigating the Uncharted Waters of a Lifestyle Medicine Fellowship.
AB  - Lifestyle medicine (LM) is now recognized as a first-line treatment and disease
      reversal program for many chronic diseases. More providers are encouraged to
      prescribe lifestyle treatments, yet lack of training, inadequate time, and poor
      reimbursement hinder many physicians from actually following through, and few LM
      specialists are available for counsel or referral. With great strides in
      resolving these dilemmas, the American College of Lifestyle Medicine has created
      standards and competencies, and the American Board of Lifestyle Medicine will be
      holding its first exam for certification in LM in October 2017. Still no
      residency or fellowship program exists to train providers to become LM
      specialists. This article describes one physician's journey through an
      unaccredited fellowship in lifestyle medicine at Black Hills Health and Education
      Center under Dr John Kelly, founding president of the American College of
      Lifestyle Medicine. Highlighting the differences of her lifestyle medicine
      training from her prior primary care and preventive medicine training, the author
      advocates for the formation of an accredited LM training program in intensive
      lifestyle medicine interventions.

PMID- 30202349
TI  - FareWell and the How of Lifestyle Medicine.
AB  - The what of Lifestyle Medicine, including a whole foods dietary pattern, has been
      well established, but the how has remained elusive. How do we apply what we know
      in a cost-effective and widely accessible manner to prevent, treat, and even
      reverse chronic disease? Over the decade ahead, we believe the field of Lifestyle
      Medicine and the people who need it most will benefit from addressing the how.
      This article summarizes the founding and operational principles of FareWell Inc. 
      a digital therapeutics company targeting lifestyle-related cardiometabolic
      diseases. We outline our current use of mobile health technology and artificial
      intelligence and describe our early clinical experience, business model, and key
      anticipated challenges.

PMID- 30202353
TI  - What Social, Program, and Behavioral Factors Influence the Healthy Eating Index
      for EFNEP and SNAP-Ed Adult Participants?
AB  - The main objectives of this article were to determine the demographic factors,
      the program related factors and the behavioral factors that influence Michigan
      Expanded Food and Nutrition Education Program and Supplemental Nutrition
      Assistance Program-Education outcomes. Secondarily, we sought to understand the
      trends and changes in Healthy Eating Index (HEI) scores across the differing
      baseline score groups. The data were collected by nutrition instructors in a
      pretest, posttest design to capture change in healthy eating habits through
      changes in HEI scores. The participants were all low-income program participants
      during the years of 2011 and 2012, living in Michigan. Findings show that eating
      habits improved most in households with weekly per-person income within $100 to
      $500, and with Caucasian females living in cities or suburbs. Improvements were
      also greater with those who took part in the Expanded Food and Nutrition
      Education Program, where the participants exhibited higher baseline frequency of
      planning meals before grocery shopping, comparing prices, and budgeting enough
      money for food and food related purchases. Overall, the average change in HEI
      scores increased by 2.3 points, however, the variability between the
      participants' changes was high, suggesting that more targeted program lessons
      might increase program efficacy, especially for those participants with high
      baseline HEI scores.

PMID- 30202351
TI  - Nonpharmacological Management of Gout and Hyperuricemia: Hints for Better
      Lifestyle.
AB  - We reviewed lifestyle factors that influence serum uric acid levels and risk of
      gout flare, and how to improve their deleterious effects. Since obesity increases
      uric acid and weight gain increases gout risk, weight reduction by daily exercise
      and limiting intake of excess calories is recommended. However, strenuous
      exercise, which causes adenine nucleotide degradation; starvation, which
      decreases uric acid excretion; and dehydration may raise the level of uric acid
      in serum and trigger gout. Increased intake of purine-rich foods, such as meat
      and seafood, raise the level of uric acid in serum and is associated with
      increased risk of gout, whereas dairy products, especially low-fat types, are
      associated with a lower risk of gout. Also, heavy alcohol drinking raises the
      uric acid level and increases the risk of gout through adenine nucleotide
      degradation and lactate production. Sweet fruits and soft drinks containing
      fructose should be moderated, since fructose may raise uric acid and increase
      gout risk through uric acid production and/or decreased excretion. On the other
      hand, the Mediterranean diet is recommended for gout patients, since it may also
      help prevent hyperuricemia. Furthermore, coffee and vitamin C supplementation
      could be considered as preventive measures, as those can lower serum uric acid
      levels as well as the risk of gout.

PMID- 30202354
TI  - Can Interpreting Nonsignificant Findings Inform the Lessons Learned From an
      Intervention?
AB  - Reducing Disability in Alzheimer's Disease (RDAD) is an evidenced-based
      intervention for individuals with dementia and their caregivers aimed at reducing
      the psychosocial strain of the caregiver and improving functional ability of the
      individual with dementia. Overall efficacy, acceptability, and feasibility
      outcomes have been published regarding RDAD; however, no specific outcome
      information has been published on the objective physical performance measures
      (PPM) of gait speed, functional reach, and balance. Data from the Replication of
      RDAD (n = 508) was utilized to test the hypothesis that each PPM would show
      change for participants who completed the program. No significant changes were
      identified in 3 PPM: gait speed (t = .24, P =.81), balance (t = .23, P = .82),
      and functional reach (t = -.55, P = .58). To strengthen the research about
      exercise interventions for individuals with dementia, discussion and
      interpretation of nonfindings is important for improving intervention designs and
      methodologies. In the case of RDAD, the intervention protocol may require a
      sufficient dosage of exercise with respect to fundamental exercise science
      principles, or there may be misalignment between the intervention and outcome
      measures.

PMID- 30202352
TI  - Impact of Health Status and Lifestyle Modifications on Vascular Structure and
      Function in Children and Adolescents.
AB  - Until recently cardiovascular disease is often thought of as a disease that
      manifests itself during middle age. Researchers and clinicians have begun to
      realize that the initial signs of cardiovascular disease begin early on in
      childhood with changes present in both vascular structure and function. This
      increased recognition has resulted in considerable effort to develop accurate and
      reliable methods to measure as well as track changes in vascular structure and
      function applicable to study this process in children and adolescents. Certain
      genetic abnormalities and chronic diseases, which present or emerge in childhood
      often result in meaningful changes to vascular structure and function, which aid
      in our understanding of the vascular disease process. In this review, we will
      discuss different methods of assessing vascular structure and function, the
      diseases in childhood associated with decrements and maladaptive changes in the
      vascular system, and whether modification of lifestyle (ie, weight loss, dietary
      and/or exercise changes) can affect vascular structure and function in children.

PMID- 30202355
TI  - Don't Forget the Brain: Lifestyle Medicine in the Century of Neurodegeneration.
AB  - Neurology is often not discussed in lifestyle medicine circles, but it might be
      an area that will propel the cause of lifestyle medicine in the future. This is
      especially relevant in increasingly common neurodegenerative conditions such as
      Alzheimer's disease, which have no known disease modifying therapy but lifestyle
      factors are implicated in causation.

PMID- 30202356
TI  - Lifestyle Medicine: Evidence, Education, and Practical Applications.

PMID- 30202357
TI  - Lifestyle Medicine 2016: Emerging Opportunities and Continuing Challenges.

PMID- 30202358
TI  - Money Talks.
AB  - The cost of providing medical care is increasing. The driving forces include
      inherent health care system conflicts of interest and financial incentives for
      procedures and technology. Effective lifestyle medicine principles are not easily
      adopted and rewarded in the present environment. Recent moves toward outcomes
      based pay systems offer the potential to demonstrate the effectiveness of
      lifestyle medicine principles while bypassing many of the biases, application
      delays, and political machinations of the traditional randomized control trial
      methodology. The American College of Lifestyle Medicine is uniquely positioned to
      be a leading organization in improving health, enhancing patient experience, and
      reducing the cost of care.

PMID- 30202359
TI  - American College of Lifestyle Medicine Expert Panel Discussion: Implementing
      Intensive Therapeutic Lifestyle Change Programs.

PMID- 30202360
TI  - Food Revolution.
AB  - Recent research has found important links between poor dietary choices, a toxic
      food environment, and high national and global burdens of chronic diseases. These
      findings serve as an impetus for a Food Revolution. The Gardner Nutrition Studies
      Research Group, along with a diverse range of collaborators, has been focusing on
      solution-oriented research to help find answers to the problems that plague the
      current food system. Research topics include (1) a recently completed weight loss
      diet study contrasting Healthy Low-Fat to Healthy Low-Carbohydrate diets among
      609 overweight and obese adults; (2) a quasi-experimental study conducted among
      Stanford undergraduates that examined social and environmental, rather than
      health-focused, motivations for dietary change; (3) links between dietary fiber,
      the human microbiome, and immune function; and (4) ongoing collaborations with
      university chefs to create unapologetically delicious food for campus dining
      halls that is also healthy and environmentally sustainable. Most of these
      approaches emphasize plant-based diets. The decreased consumption of animal
      products has created some concern over the ability of one to obtain adequate
      protein intake. Evidence is presented that adequate protein is easily obtainable
      from vegetarian, vegan, and other diets that contain significantly less meat and
      fewer animal foods than the standard American diet.

PMID- 30202361
TI  - Medication Adherence, When Lifestyle Is the Medicine.
AB  - Giving patients insight, knowledge, and skills, although important, may not alone
      be enough for behavior change maintenance. Rather, the health care provider (HCP)
      has an important role in fostering behavior change and maintenance by asking,
      "Why do people change?" and "What can I do to help?" This review highlights 4
      evidence-based factors related to medication adherence, when lifestyle is the
      medicine. (1) Autonomy is the belief that one is the origin of his or her own
      actions, and must be supported by the HCP (eg, "My HCP listens to how I would
      like to do things regarding my health"). (2) Competence and confidence ensure
      that patients believe they can succeed. These are gained through mastery
      experience, vicarious experience, and through positive and constructive feedback
      on past performance (eg, "My HCP conveys confidence in my ability to make changes
      regarding my health"). (3) Coping planning is being able to formulate a plan of
      intention, with the awareness of barriers and emotional regulation that can
      inhibit patient behavior (eg, "I feel able to share my feelings with my HCP").
      (4) Personal values of the patients are used to understand how and why they cope
      when there is a threat to these values (eg, "My HCP tries to understand how I see
      my health before suggesting any changes").

PMID- 30202362
TI  - How to Create a Successful Lifestyle Medicine Practice.
AB  - A lifestyle medicine (LM) practice aims to treat the whole person, with a focus
      on addressing the root lifestyle causes of disease. Creating a practice in LM
      comes with an array of challenges. Utilizing different payment systems and
      practice models, such as cash, traditional insurance, Direct Primary Care model,
      or concierge systems, allows for the incorporation of more LM services and
      ensures sustainability in the practice. One must develop a sound business model
      and aim to keep costs low. Optimizing coding, taking advantage of additional LM
      services, and expanding service formats to group visits or telemedicine are all
      creative ways to incorporate and develop LM practices. Anticipation of new
      challenges and flexibility in practice models and payment systems allows one to
      be successful in starting or transitioning to an LM practice.

PMID- 30202363
TI  - The Art and Science of Group Visits in Lifestyle Medicine.
AB  - Lifestyle medicine group sessions present a promising approach to clinical care.
      Based on decades of work in shared medical appointments and group visits for
      diabetes and other chronic conditions, a lifestyle medicine group session has the
      potential to provide a fresh and rewarding way of interacting with patients that
      fuels the practitioner and feeds patients' needs to spend time with the lifestyle
      medicine practitioner, connect with him or her, connect with others, learn the
      latest recommendations regarding healthy habits, practice these behaviors, and
      discuss their obstacles, motivations, and strategies for healthy living. The
      lifestyle medicine group session discussed in this article is a combination of
      group coaching, education, and group support.

PMID- 30202364
TI  - A Comprehensive Clinical Lifestyle Medicine Specialty Fellowship Program: What
      Intensive Lifestyle Treatment Can Do.
AB  - Lifestyle medicine (LM) is recognized as an essential component of evidence-based
      medical treatment, particularly for chronic diseases. Multiple studies have shown
      that intensive therapeutic lifestyle change can arrest and reverse disease,
      including heart disease, type 2 diabetes, essential hypertension, metabolic
      syndrome, and autoimmune and inflammatory conditions. While more modest lifestyle
      changes can slow the onset or prevent disease, studies reveal that intensive
      therapeutic changes are required to arrest and reverse disease. As increasing
      numbers of clinicians have learned about the powerful treatment effects of
      intensive lifestyle interventions, interest in LM has greatly increased. This, in
      turn, has led to the need for evidence-based clinical LM training in how to
      effectively provide intensive LM interventions that can arrest and reverse
      disease. As with all clinical training, such training must include actual patient
      care guided by knowledgeable expert LM clinicians. The purpose of this article is
      to (1) describe the need for and function of clinical LM specialists, (2)
      describe the key components in the training of clinical LM specialists to treat
      and reverse chronic disease, and (3) describe the steps/components in
      establishing and implementing a clinical LM specialty-training program.

PMID- 30202365
TI  - Managing Problem Drinking: Screening Tools and Brief Interventions for Primary
      Care Physicians.
AB  - A high percentage of patients seen in primary care clinics partake in excessive
      alcohol consumption. It leads to numerous health problems and remains one of the
      leading risk factors for chronic disease. Despite the health concerns, screening
      for and intervening in patients' alcohol misuse has yet to become standard
      practice in many primary care settings. There is well-established empirical
      evidence that brief doctor-patient interactions reduce alcohol consumption among
      excessive drinkers in primary care settings. This article draws on randomized
      controlled trials and literature on screening techniques, motivational
      interviewing, the transtheoretical model of behavior change, and medication
      assisted treatments to enhance brief intervention methodology. Through this
      review, evidence-based practical strategies are presented to primary care doctors
      that reduce alcohol consumption in patients screened as problem drinkers.
      Referral information for those individuals with severe drinking problems is
      included. We propose that short, multicomponent interventions are most effective
      when they include interventions that utilize the lifestyle medicine philosophy, a
      nonjudgmental therapeutic alliance, and account for patient concerns more
      directly.

PMID- 30202366
TI  - Alcohol Use in Young Adults With Type 1 Diabetes Mellitus.
AB  - Although fewer individuals with type 1 diabetes mellitus (T1DM) drink alcohol,
      the potential and severity of harm associated with its consumption is higher in
      persons with diabetes. Alcohol use affects glucose metabolism and results in
      various potential adverse effects both from acute ingestion and chronic ingestion
      in persons with T1DM. The purpose of this article is to describe the effects of
      alcohol on glucose metabolism and diabetes control in persons with T1DM and
      propose counseling pearls for providers working with patients in this population.

PMID- 30202368
TI  - Proactive Living: A Unique Model for the Promotion of Lifestyle Medicine.
AB  - Lifestyle medicine (LM) is a growing field focused on maintenance of health and
      reversal of chronic diseases; however, it is still unfamiliar to many as it lacks
      a mechanism to set itself apart from other medical specialties, which focus
      primarily on management of established diseases and their symptoms. Given that
      employers have many incentives to maintain and improve the health of their
      employees, the corporate wellness space (corporate wellness) represents a
      considerable opportunity for LM. Proactive Living, a company at the confluence of
      LM and corporate wellness, promotes and connects LM practitioners with employers
      and employees through a mobile app (PAL App). The app is designed to improve
      health literacy, encourage healthy lifestyle behaviors, and engage individuals in
      their own health, while simultaneously helping LM practitioners market LM and
      grow their practice.

PMID- 30202367
TI  - When Diet and Exercise Aren't Enough: The Added Benefits of Connection,
      Community, and Psychosocial Support in Navigating Breast Cancer Treatment.
AB  - Breast cancer is the most common cancer diagnosis in women, and many lifestyle
      factors have been linked to an elevated risk for development of the disease. This
      case provides an example of how breast cancer can occur even in people who engage
      in healthy lifestyle behaviors, yet underscores the importance of exercise,
      healthy dietary patterns, and addressing psychological distress in supporting
      women through their treatment and beyond.

PMID- 30202370
TI  - Back to Basics.
AB  - Non-drug therapy should be foundational to our treatment plans. These should be
      evidence-based. Drug based therapies rely heavily on randomized controlled trials
      while the evidence many lifestyle interventions relies more heavily on
      epidemiological studies. Both have weaknesses and strengths. Medicine needs a
      system for evaluating evidence that recognizes the strengths of both types of
      studies and includes some common measure such as Number Needed to Treat (NNT) and
      Number Needed to Harm (NNH).

PMID- 30202369
TI  - Planting the Seeds of Change: Growing Lifestyle Medicine Interest Groups With the
      Donald A. Pegg Award.
AB  - The practice of Lifestyle medicine (LM) focuses on helping patients make healthy
      choices to prevent and treat disease. While such interventions are considered
      first-line treatment for many diseases, many medical schools have not yet been
      able to include lifestyle medicine classes in the core curriculum but most are
      able to offer a parallel curriculum that does not interfere with the schedule of
      core classes. Lifestyle Medicine Interest Groups (LMIGs) are being created around
      the country and around the globe. Many students and faculty members are
      interested in starting and sustaining a LMIG at their schools, but some do not
      have enough funding or they lack the framework that provides structure to their
      efforts. To address this situation, the American College of Lifestyle Medicine
      (ACLM) has encouraged the development of LMIGs, which are student-run
      organizations that provide a parallel curriculum in LM. To support and strengthen
      this effort, the ACLM initiated the Donald A. Pegg award to fund four allied
      health students in founding and augmenting their institution's LMIGs. The 2016
      inaugural winners were James Gardner, P. Elainee Poling, Alyssa Abreu, and Jessie
      M. Hipple. Their LMIG activities have included events such as nutrition and
      cooking classes, exercise prescription seminars, group fitness sessions, and
      patient lifestyle counseling in various clinical settings. Pearls of wisdom for
      building successful LMIGs include cultivating strong faculty mentorship,
      marketing the personal benefits to students who attend activities, and
      collaborating with other student groups.

PMID- 30202371
TI  - Creating a Trauma-Sensitive Practice: A Health Care Response to Interpersonal
      Violence.
AB  - Interpersonal violence has a profoundly negative impact on individuals and our
      society. Health care providers are in a unique position to identify interpersonal
      violence, support survivors, and to contribute to violence prevention. The
      purpose of this article is to describe the nature, scope, and impact of
      interpersonal violence, its subsequent trauma on individuals, families, and
      society, and to delineate how providers can apply trauma-sensitive practice. The
      authors provide definitions, examples and prevalence rates and review theories of
      violence and violence prevention. They describe how to create a trauma-sensitive
      practice by being aware of the trauma that accompanies violence, the barriers to
      violence prevention, and how to intervene with patients about violence. Providers
      are urged to adopt universal screening practices, educate themselves on the
      nature of interpersonal violence and engage in screening, education,
      collaboration, and social justice activities to reduce interpersonal violence.
      Resources are provided to assist health care organizations, providers, and
      patients in addressing interpersonal violence.

PMID- 30202372
TI  - The Connection Prescription: Using the Power of Social Interactions and the Deep
      Desire for Connectedness to Empower Health and Wellness.
AB  - Social connection is a pillar of lifestyle medicine. Humans are wired to connect,
      and this connection affects our health. From psychological theories to recent
      research, there is significant evidence that social support and feeling connected
      can help people maintain a healthy body mass index, control blood sugars, improve
      cancer survival, decrease cardiovascular mortality, decrease depressive symptoms,
      mitigate posttraumatic stress disorder symptoms, and improve overall mental
      health. The opposite of connection, social isolation, has a negative effect on
      health and can increase depressive symptoms as well as mortality. Counseling
      patients on increasing social connections, prescribing connection, and inquiring
      about quantity and quality of social interactions at routine visits are ways that
      lifestyle medicine specialists can use connection to help patients to add not
      only years to their life but also health and well-being to those years.

PMID- 30202373
TI  - Prescribing a Healthy Lifestyle Polypill With High Therapeutic Efficacy in Many
      Shapes and Sizes.
AB  - The paradigm allowing for a lifestyle immersed in unhealthy behaviors to
      perpetuate to a point where a non-communicable disease (NCD) is eminent or
      manifests, and then initiating health care interventions, is deeply flawed,
      results in poor outcomes, and is unsustainable. This paradigm describes the
      current predominant healthcare model in many countries around the world and has
      resulted in the continual increase in unhealthy lifestyle patterns that have led
      to the global NCD epidemic. It is now broadly recognized that rapid integration
      of a new healthcare model, one heavily focused on primordial and primary NCD
      prevention, is needed. Being physically active, eating healthy and nutritious
      foods, not smoking and minimizing second-hand exposure, and maintaining an
      appropriate body weight are central to this new prevention model. Combined, these
      four characteristics can be viewed as the key ingredients for the "healthy
      lifestyle polypill". Recently, the American Heart Association (AHA), European
      Society of Cardiology (ESC), European Association for Cardiovascular Prevention
      and Rehabilitation (EACPR), and American College of Preventive Medicine (ACPM)
      came together to publish, in both the Mayo Clinic Proceedings and European Heart
      Journal, a policy statement entitled "Healthy Lifestyle Interventions to Combat
      Non-Communicable Disease: A Novel Non-Hierarchical Connectivity Model for Key
      Stakeholders". We hope the AHA-ESC-EACPR-ACPM healthy lifestyle policy statement
      prompts a massive increase in production of the healthy lifestyle polypill.
      Regulatory approval is not needed to start manufacturing and distributing this
      medication. The polypill can take many forms and have differing ingredients and
      dosages while still maintaining high therapeutic efficacy.

PMID- 30202374
TI  - Impact of a University-Community Partnership Approach to Improving Health
      Behaviors and Outcomes Among Overweight/Obese Hispanic Adults.
AB  - Objective. To examine the impact of a community-informed and community-based
      Health-Smart Church (HSC) Program on engagement in health promoting behaviors
      (healthy eating and physical activity) and health outcomes (body mass index,
      weight, and systolic and diastolic blood pressure). Design. A total of 70
      overweight/obese Hispanic adults participated in an intervention group (n = 37)
      or a waitlist control group (n = 33) in 2 Hispanic churches in Bronx, New York.
      Results. Post-intervention the intervention group significantly increased in
      frequency of healthy eating and physical activity compared to the waitlist
      control group. Although no significant changes in body mass index or systolic
      blood pressure were found for either group, the intervention group decreased
      significantly in weight from pre-intervention to post-intervention. Conclusions.
      The results of the present study add to the growing body of literature evidencing
      the successful use of community-engaged and community-based participatory health
      promotion interventions with racial/ethnic minority populations and highlight
      important practices and considerations for similar health promotion interventions
      with these communities.

PMID- 30202375
TI  - Physical Activity Level Is Associated With Maintaining Anthropometric
      Improvements Among Participants in a Worksite Wellness Program.
AB  - Background. Physical activity (PA) can facilitate weight loss, help avoid weight
      regain, and improve body composition. This study examined the relationships
      between PA level and changes in anthropometric measures among university
      employees in a worksite wellness program. Methods. A registered dietitian
      provided individualized assessments at baseline followed by a 12-week education
      intervention with follow-up at 12 and 26 weeks. The International Physical
      Activity Questionnaire-Short Form was used to calculate PA <=150 or >=150 min/wk,
      median min/wk, and metabolic equivalent of task (MET) min/wk at each time point.
      Repeated-measures general linear model and nonparametric tests were used to
      assess significant differences over time. Results. Of the 64 participants, 89%
      were women and 50% were non-Hispanic white. At 12 and 26 weeks, participants
      experienced significant decreases in weight (P = .001). Among women, waist
      circumference and abdominal obesity decreased significantly (P < .01). PA >=150
      min/wk (n = 21) was associated with continued weight loss (P = .03) and decreases
      in body fat percentage (P = .02) between 12 and 26 weeks whereas PA <=150 min/wk
      was associated with weight and body fat percentage regain during the same time
      period. Conclusion. Among women in a worksite wellness program, higher levels of
      PA were associated with avoiding weight and body fat regain following successful
      loss.

PMID- 30202377
TI  - Epidural Lipomatosis and Associated Spinal Stenosis-The Impact of Weight Loss: A
      Case Report.
AB  - Lumbar stenosis is a common radiographic finding that sometimes can be
      symptomatic. It usually results from a degenerative process of hypertrophic
      facets, ligamentum flavum hypertrophy, and disc involvement. A prominence of fat
      in the epidural space, epidural lipomatosis, can also be a contributing factor.
      This case report presents a 55-year-old man with radiographic improvement of
      epidural lipomatosis and stenosis from dietary weight loss. Given the rising
      obesity epidemic, practitioners should be cognizant of epidural lipomatosis and
      consider weight loss as a possible treatment option.

PMID- 30202376
TI  - Associations Among Leisure-Time Physical Activity, Gestational Weight Gain, and
      Postpartum Weight Retention With Varying Estimates of Prepregnancy Weight.
AB  - Prospective studies examining postpartum weight retention (PPWR) in relation to
      the appropriateness of gestational weight gain (GWG) and leisure-time physical
      activity (LTPA) during pregnancy and postpartum are lacking. While utilizing
      varying estimates of prepregnancy weight, we sought to prospectively examine
      associations among the aforementioned variables. Our sample consisted of a subset
      of women from the Archive for Research on Child Health Study (n = 68).
      Prepregnancy weight was obtained via questionnaire and birth certificates. GWG (2
      estimates) was calculated by subtracting prepregnancy weight estimates from
      weight at delivery and classified as "excess" or "not excess." Pregnancy and
      postpartum LTPA were self-reported and dichotomized at recommended levels.
      Prepregnancy weight estimates were subtracted from self-reported postpartum
      weight to calculate 2 estimates of PPWR at 6 months. Linear regression was used
      to examine relationships among GWG and LTPA, and PPWR. Estimates of excess GWG
      were associated with increased PPWR (mean difference = 3.3-8.9 kg), even after
      adjustment for prepregnancy body mass index and breastfeeding. Meeting pregnancy
      and postpartum LTPA recommendations did not significantly predict PPWR. Our
      findings highlight the importance of encouraging appropriate GWG and provide
      insight into the impact varying estimates of prepregnancy weight may have when
      exploring associations among these variables.

PMID- 30202379
TI  - Considerations for Evaluation of Diabetes Prevention Programs in Hispanic Adults
      in the United States.
AB  - Hispanics are at high risk for diabetes. While there have been a number of
      diabetes prevention programs targeting Hispanics in the United States, not all
      recent studies focused on evaluating such programs have made use of validated
      tools to examine behavior change or examined acceptability and feasibility of the
      intervention. Tools used to assess behavioral outcomes such as diet should be
      tested to ensure validity and reliability. Acceptability may be examined using
      qualitative and quantitative measures to obtain feedback on the content of the
      intervention. Feasibility of the intervention may be evidenced by the enrollment,
      attendance, and attrition rates, as well as barriers or facilitators to
      participating in the program. Appropriate and comprehensive evaluation of such
      programs will allow for continued improvement of prevention efforts to address
      high rates of diabetes in this at-risk population.

PMID- 30202380
TI  - Helping Bodies in Motion Stay in Motion Through a Unique Model of Care.
AB  - There are many inherent challenges associated with the development of an
      effective lifestyle medicine practice that is financially viable. There exist
      numerous proposed practice models, many of which show promise. Inertia Medical
      represents a model of combined care through which services related to
      musculoskeletal and lifestyle medicine are offered in a part-time, self-pay, solo
      practice. Central to the framework of Inertia Medical is simplicity. The small
      practice structure allows patients to feel closely connected to the provider and
      directly involved in their own health care. Minimal overhead costs and limited
      administrative tasks allow more time, energy, and resources to be focused on what
      matters most-delivering high-quality patient care. The simple design has become a
      distinguishing characteristic of this practice and could allow other health care
      providers to adopt a similar model.

PMID- 30202381
TI  - Cummins' Vision: Improved Health Through Lifestyle Medicine Innovation.
AB  - The importance of lifestyle for overall health and well-being cannot be
      overstated. By Centers for Disease Control and Prevention estimates, nearly 80%
      of many chronic conditions such as heart disease and type 2 diabetes are
      preventable through the adoption of healthier lifestyles. Yet, while preventable,
      these common illnesses account for the majority of the rising US health care
      costs. For nearly a century, Cummins Inc, a large global employer headquartered
      in Columbus, Indiana, that designs, manufactures, distributes, and services
      diesel and natural gas engines and related technologies, has demonstrated a
      penchant for innovation. However, in the area of health improvement, the company
      believed it could do better and decided to address the prime factor-lifestyle-the
      root cause of the growing problem of chronic disease for its employees and their
      families. This report offers a glimpse into Cummins' forward-thinking strategy
      and their early efforts to combat preventable chronic disease through lifestyle
      and lifestyle medicine.

PMID- 30202378
TI  - Lifestyle and the Prevention of Type 2 Diabetes: A Status Report.
AB  - Diabetes is a costly disease affecting 387 million individuals globally and 28
      million in the United States. Its precursor, prediabetes, affects 316 and 86
      million individuals globally and in the United States, respectively. People
      living with elevated blood glucose levels are at high risk for all-cause
      mortality and numerous cardiometabolic ailments. Fortunately, diabetes can be
      prevented or delayed by maintaining a healthy lifestyle and a healthy body
      weight. In this review, we summarize the literature around lifestyle diabetes
      prevention programs and provide recommendations for introducing prevention
      strategies in clinical practice. Overall, evidence supports the efficacy and
      effectiveness of lifestyle diabetes prevention interventions across clinical and
      community settings, delivery formats (eg, individual-, group-, or technology
      based), and implementers (eg, clinicians, community members). Evidence-based
      diabetes prevention strategies that can be implemented in clinical practice
      include brief behavior change counseling, group-based education, community
      referrals, and health information technologies. These strategies represent
      opportunities where practitioners, communities, and health care systems can work
      together to provide individuals with education, support and opportunities to
      maintain healthy, diabetes-free lifestyles.

PMID- 30202382
TI  - Specific Strategies for Promotion of Physical Activity in Kids-Which Ones Work? A
      Systematic Review of the Literature.
AB  - The purpose of this systematic review was to summarize and evaluate the impact of
      physical activity (PA) interventions that were implemented in specific school
      settings on children's PA in those settings. Four research databases were
      searched to identify PA interventions. Of the 13 706 articles identified, 1352
      abstracts were screened and 32 intervention studies were reviewed. Five
      intervention settings were identified (active travel, after school, classroom,
      physical education, and recess). Among these settings, a greater proportion of
      positive findings (ie, significant increase in PA) were found in the classroom
      (75%) and active travel (67%) settings. Additionally, a higher proportion of
      interventions implemented in these settings were of high methodological quality
      (active travel [33%] and classroom [33%]). These findings indicate that
      interventions in active travel and classrooms settings positively influence youth
      PA. Importantly, as evidenced in this review, evaluating intervention effects in
      the targeted setting may provide unique information for future researchers to
      consider when developing school-based multicomponent PA interventions.

PMID- 30202384
TI  - A Micropractice/Community Partnership Model for Lifestyle Medicine.
AB  - Lifestyle medicine (LM) has been shown to be effective at preventing and
      reversing disease, while simultaneously reducing overall medical expenses.
      However, the current health care system is not designed to reimburse LM
      clinicians for the value that they provide. The micropractice model is an
      innovative approach to deliver LM in a financially viable manner. Costs are
      minimized by automating much of the practice through a website, limiting physical
      clinic space, and employing only essential staff. Described in this article is a
      unique micropractice family medicine/lifestyle medicine hybrid office that has
      partnered with a local health system and a culinary center to offer additional
      services.

PMID- 30202383
TI  - A Brief Mindfulness-Based Intervention for Primary Care Physicians: A Pilot
      Randomized Controlled Trial.
AB  - Primary care physicians experience high rates of burnout, which results in
      diminished quality of life, poorer quality of care, and workforce attrition. In
      this randomized controlled trial, our primary aim was to examine the impact of a
      brief mindfulness-based intervention (MBI) on burnout, stress, mindfulness,
      compassion, and resilience among physicians. A total of 33 physicians completed
      the baseline assessment and were randomized to the Mindful Medicine Curriculum
      (MMC; n = 17) or waitlist control group (n = 16). Participants completed self
      report measures at baseline, post-MBI, and 3-month follow-up. We also analyzed
      satisfaction with doctor communication (DCC) and overall doctor rating (ODR) data
      from patients of the physicians in our sample. Participants in the MMC group
      reported significant improvements in stress (P < .001), mindfulness (P = .05),
      emotional exhaustion (P = .004), and depersonalization (P = .01) whereas in the
      control group, there were no improvements on these outcomes. Although the MMC had
      no impact on patient-reported DCC or ODR, among the entire sample at baseline,
      DCC and ODR were significantly correlated with several physician outcomes,
      including resilience and personal achievement. Overall, these findings suggest
      that a brief MBI can have a positive impact on physician well-being and
      potentially enhance patient care.

PMID- 30202385
TI  - Contemporary Approaches to Prescribing Exercise in Coronary Artery Disease
      Patients.
AB  - Health care professionals engaged in the management of coronary artery disease
      (CAD) patients, both in primary and secondary prevention settings, should possess
      the knowledge to develop and modify both aerobic exercise as well as
      musculoskeletal resistance exercise training programs. The traditional exercise
      prescription (ExRx) for aerobic-type exercise describes the intensity, frequency,
      duration, and mode of exercise, as well as the rate of progression. The more
      contemporary ExRx focuses on the energy expenditure associated with all physical
      activity not just structured exercise bouts. The total "volume or dose" of
      physical activity is associated with important health outcomes, including the
      potential to prevent and potentially reverse CAD lesions. Also, emerging evidence
      supporting the use of high-intensity interval training in CAD patients will also
      be provided. Furthermore, this review will also address the issue of generating
      an appropriate ExRx in the absence of maximal exercise "stress" test data, a
      common occurrence in the primary care setting and in this era of health care cost
      containment. Prescribing resistance exercise for CAD patients requires careful
      consideration and will be discussed in this review. Finally, this review will
      conclude with a section that describes the special considerations and/or
      modifications for some common comorbidities seen in CAD patients.

PMID- 30202388
TI  - Improving Nutritional Habits With No Diet Prescription: Details of a Nutritional
      Coaching Process.
AB  - Thousands of dollars are spent today with policies encouraging physical activity
      and healthy eating, but nutritional consultation per se has continuously failed
      to yield consistent and lasting results. The aim of this case report is to detail
      and evaluate nutritional coaching (employing health coaching techniques) in
      promoting lifestyle changes, enabling improvement of nutritional and body
      composition associated parameters. The patient in this study had previously
      engaged in a series of different diet regimens, all of which failed in achieving
      the proposed aim. After 12 nutritional coaching sessions (one per week) with the
      strategy presented herein, reductions in body fat mass and in total body weight
      were attained. Nutritional habits also improved, as the patient showed decreased
      total energy intake, decreased fat intake, and increased fiber ingestion. Daily
      physical activity and energy expenditure were enhanced. The coaching program was
      able to induce immediate health benefits using a strategy with the patient at the
      core of promoting his own lifestyle changes. In conclusion, the nutritional
      coaching strategy detailed was effective at helping our patient develop new
      eating patterns and improve related health parameters.

PMID- 30202386
TI  - Lifestyle Modification for Secondary Stroke Prevention.
AB  - Of nearly 800 000 strokes that occur annually, 23% are recurrent events. Risk for
      disability and mortality is higher following a recurrent stroke than following a
      first-time stroke, which makes secondary stroke prevention a priority. Many risk
      factors for stroke are modifiable and amenable to improvement through lifestyle
      modification. Lifestyle modification can be difficult for people with stroke,
      however, in part because of stroke-related physical and cognitive deficits.
      Despite these challenges, risk factor management through lifestyle modification
      is important. This article reviews the multiple cardiovascular and metabolic
      benefits associated with the modification of several lifestyle behaviors: diet,
      physical activity, smoking cessation, and alcohol consumption. Health behavior
      theories and existing lifestyle intervention programs are also reviewed to
      identify important behavioral and cognitive skills that can be used to facilitate
      modification of health behaviors, and practical skills and suggestions for health
      care providers are provided.

PMID- 30202387
TI  - Fundamental Movement Skills and Health-Related Outcomes: A Narrative Review of
      Longitudinal and Intervention Studies Targeting Typically Developing Children.
AB  - Many children with typical development are highly sedentary, overweight/obese,
      and are deemed not ready for school at kindergarten entry. All of these concerns
      can be related to a lack of movement skill proficiency in this population. The
      purpose of this narrative review was to synthesize the literature examining the
      impact of movement skills on 5 areas of overall health: physical activity,
      physical fitness, body composition, self-beliefs, and executive functioning. To
      gain an understanding of these relationships, only studies employing an
      experimental or observational longitudinal design were reviewed. Although the
      results were limited in the number of studies available, there is evidence that
      movement skill may have a positive influence on these broad domains of health
      both naturally over the course of development and through intervention. We
      recommend that a universal approach to movement skill development is warranted,
      given the range of benefits that stem from developing proficiency in these
      skills.

PMID- 30202390
TI  - Primary Care-Based Health Coaching for the Management of Prediabetes.
AB  - Introduction. Prediabetes is a prevalent disease that has been associated with
      its own health risks and is a known precursor of type 2 diabetes. Lifestyle
      interventions are known to effectively treat prediabetes but are often not
      offered to patients within a primary care setting. Study Design. Exploratory and
      descriptive study. Objective. To assess if the use of a health coaching
      intervention among primary care patients, with prediabetes, warrants further
      examination. Methods. A retrospective chart review was conducted for all patients
      who had prediabetes and received health coaching at the Ambulatory Practice of
      the Future between 2012 and 2014. Discussion. A health coaching intervention used
      among primary care patients, with prediabetes, deserves further examination, as
      participants had a significant reduction in hemoglobin A1c and weight over 2
      years.

PMID- 30202389
TI  - Effect of Online Training on Antenatal Physical Activity Counseling.
AB  - Objective: The objective of this study was to test the effect of an online
      education intervention on providers' attitudes, beliefs, knowledge, and practices
      pertaining to antenatal physical activity. Study design: A sample of 181
      providers (ie, obstetricians, family medicine physicians, and certified nurse
      midwives) was directed to view an online training on antenatal physical activity
      guidelines, counseling methods, and resources. Providers completed surveys before
      and 12 weeks after viewing the educational website material. Repeated-measures
      analyses were conducted to examine the effects of the online education. Results:
      A total of 164 providers (87.2%) completed baseline and follow-up surveys. After
      viewing the online training, participants more strongly agreed that it was their
      responsibility to encourage engagement in antenatal physical activity (P = .02)
      and believed that women would follow their advice about beginning antenatal
      physical activity (P = .01). Viewing the website material facilitated an
      increased confidence in ability to effectively talk with overweight and obese
      women about physical activity (P = .04) and more frequent advising to begin a
      moderate-intensity physical activity program for sedentary women (P = .02).
      Knowledge on antenatal physical activity guidelines also improved. Conclusion:
      Findings suggest that online educational interventions may be an effective tool
      in altering providers' knowledge and practices pertaining to antenatal physical
      activity.

PMID- 30202392
TI  - Cancer Epidemiology: A Survey of Modifiable Risk Factors for Prevention and
      Survivorship.
AB  - Approximately 40% of men and women in the United States will be diagnosed with
      cancer at some point in their lives. There have been dramatic developments in our
      understanding of cancer development and progression in recent decades, leading to
      improvements in screening and treatment, and in turn greater numbers of survivors
      living longer after diagnosis. Epidemiologic evidence of lifestyle-related
      factors and cancer risk and survival has been explored extensively in the
      published literature, with recommendations for cancer prevention and control and
      strategies for implementation evolving over time. This review summarizes the
      burden of cancer, general measurement issues in cancer epidemiology, and the
      current state of the science in specific lifestyle-related risk factors and
      cancer. It is estimated that one third to one half of cancers could be prevented
      by healthier lifestyle choices.

PMID- 30202391
TI  - Promoting Healthy Eating and Physical Activity Behaviors: A Systematic Review of
      Multiple Health Behavior Change Interventions Among Cancer Survivors.
AB  - Multiple health behavior change (MHBC) interventions have great potential for
      enhancing health and well-being following cancer diagnosis and treatment.
      However, the characteristics and effects of MHBC interventions remain elusive for
      cancer survivors. The main purpose of this study was to evaluate the
      effectiveness of MHBC interventions on healthy eating and physical activity
      behaviors among cancer survivors. A secondary aim was to examine the effect of
      using a simultaneous and sequential design approach to MHBC (ie, changing both
      behaviors at the same time or one after the other). Randomized controlled trials
      reporting the impact of a MHBC intervention on both healthy eating and physical
      activity behaviors among cancer survivors were retrieved from MEDLINE, Cochrane
      Library, and PsycINFO. A total of 27 MHBC interventions were identified; most
      (92.6%) were designed to promote simultaneous change in both behaviors and
      assessed end-of-treatment effect among breast cancer survivors. MHBC
      interventions led by nurses or multidisciplinary teams showed the most compelling
      evidence for small to moderate improvement in both behaviors, with interventions
      that lasted >=17 weeks more likely to improve both behaviors. This study
      identifies research priorities and provides preliminary evidence for clinical
      decision making and advancements in MHBC intervention design and delivery for
      clinical oncology.

PMID- 30202396
TI  - Preserving Care Delivery in Hard-to-Serve Regions: A Case Study of a Population
      Health System in the Swiss Lower Engadin.
AB  - Introduction: Many countries report difficulties in preserving access to care in
      rural areas. This paper examines how hard-to-serve regions sustain care provision
      by transforming service delivery into population health systems. Theory and
      methods: The paper builds on theory on care delivery in hard-to-serve regions. It
      presents a qualitative case study from the Lower Engadin, a rural high mountain
      valley in the Swiss Alps. Data sources include semi-structured interviews,
      participant observations, and documents. Data are analysed using recent
      conceptual research on population health systems. Results: The case study
      illustrates how politicians and providers in the Lower Engadin resolved a care
      crisis and preserved access to care by forming a population health system. The
      system is organised around the Healthcare Centre Lower Engadin. Citizen-centred
      interventions target an aging population and include health promotion and
      prevention programs as well as case management based on an ambulatory-before
      inpatient care strategy. Conclusion: Hard-to-serve regions like the Lower Engadin
      preserve access to care by reorganising service delivery towards population
      health systems. The paper contributes to research on population health systems
      and care provision in rural areas.

PMID- 30202393
TI  - Encouraging Dog Walking for Health Promotion and Disease Prevention.
AB  - Regular physical activity is associated with numerous health benefits, including
      the prevention of many chronic diseases and conditions or a reduction in their
      adverse effects. Intervention studies suggest that promoting dog walking among
      dog owners who do not routinely walk their dogs may be an effective strategy for
      increasing and maintaining regular physical activity. Strategies that emphasize
      the value of dog walking for both dogs and people, promote the context-dependent
      repetition of dog walking, enhance the social-interaction benefits, encourage
      family dog walking, and ensure availability of public space for dog walking may
      encourage increased dog walking. Research also supports organizing buddy systems
      via "loaner" dogs to facilitate informal walking by dog owners and non-dog
      owners. Given the number of homes that have dogs, strategies that promote dog
      walking could be effective at increasing physical activity levels among a
      significant proportion of the population. Maximizing the potential for dog
      walking to positively influence the health of individual people (and dogs) will
      only occur through implementing programs with broad population-level reach.
      Policies that facilitate dog walking at the community and population levels, such
      as "dogs allowed" places, off-leash zones, and dog-friendly built environments
      and parks, may contribute to greater physical activity through dog walking.

PMID- 30202394
TI  - The Obesity Paradox in Type 2 Diabetes and Mortality.
AB  - The obesity paradox for survival among individuals with type 2 diabetes has been
      observed in some but not all studies. Conflicting evidence for the role of
      overweight and obesity in all-cause mortality may largely be a result of
      differences in study populations, epidemiological methods, and statistical
      analysis. For example, analyses among populations with long-term prevalent
      diabetes and the accrual of other chronic health conditions are more likely to
      observe that the sickest participants have lower body weights, and therefore,
      relative to normal weight, overweight and even obesity appear advantageous. Other
      mortality risk factors, such as smoking, also confound the relationship between
      body weight and survival, but this behavior varies widely in intensity and
      duration, making it difficult to assess and effectively adjust for in statistical
      models. Disentangling the potential sources of bias is imperative in
      understanding the relevance of excess body weight to mortality in diabetes. In
      this review, we summarize methodological considerations underlying the observed
      obesity paradox. Based on the available evidence, we conclude that the obesity
      paradox is likely an artifact of biases, and once these are accounted for, it is
      evident that compared with normal body weight, excess body weight is associated
      with a greater mortality risk.

PMID- 30202395
TI  - Diabetes Diagnosis and Screen-Based Sedentary Behavior Among US Adults.
AB  - Diabetes threatens a patient's health and quality of life, whereas disease
      diagnosis itself could potentially serve as a teachable moment for initiating
      behavior change. This study assessed diabetes diagnosis as a possible teachable
      moment for screen-based sedentary behavior among US adults. The nationally
      representative sample (n = 3690) came from the 2005-2006 and 2011-2012 National
      Health and Nutrition Examination Survey. Self-reported hours spent on screen
      based sedentary behavior (television/video watching, computer/digital device use)
      were measured by the Global Physical Activity Questionnaire. Diabetes/prediabetes
      was identified by fasting plasma glucose and the glycated hemoglobin test.
      Logistic regressions were conducted to examine the relationship between diabetes
      diagnosis and screen-based sedentary behavior, adjusting for individual
      characteristics and sampling design. Compared with those with undiagnosed
      diabetes, the adjusted values for prevalence of daily television/video watching
      >=2 hours (77.45% vs 65.14%), computer/digital device use >=1 hour (43.20% vs
      36.52%), and total screen time (ie, television/video watching plus
      computer/digital device use) >=3 hours (66.75% vs 45.78%) were all noticeably
      higher among adults with diagnosed diabetes, although only the difference in the
      prevalence of daily total screen time was significant at P < .05. No evidence was
      found regarding diabetes diagnosis as a teachable moment in reducing screen-based
      sedentary behavior in US adults.

PMID- 30202397
TI  - "Not just dogs, but rabid dogs": tensions and conflicts amongst research
      volunteers in Malawi.
AB  - Building trust between researchers and communities involved in research is one
      goal of community engagement. This paper examines the implications of community
      engagement for trust within communities, including trust among community
      volunteers who assist with research and between these volunteers and other
      community members. We describe the experiences of two groups of community
      volunteers recruited as part of an HIV and TB intervention trial in Malawi:
      cluster representatives, recruited both to act as key informants for TB suspects
      and mortality reporting and to identify and report community concerns, and
      community counsellors, recruited to provide semi-supervised HIV self-testing. We
      examine tensions experienced due to playing multiple roles, and the implications
      of volunteer responsibilities for short- and long-term community relationships.
      Data was collected through a workshop, in-depth interviews and focus group
      discussions with volunteers and community members. While the volunteer system
      initially enhanced trust among volunteers and with the community, relationships
      deteriorated when cluster representatives assumed an additional supervisory role
      part-way through the trial. Combined with challenging recruitment targets and
      unequal power relations between volunteers, this new role damaged trust, with
      implications for volunteer well-being and social relationships. These experiences
      suggest researchers should consider potential social implications when designing
      community engagement systems.

PMID- 30202400
TI  - Prevalence and prevention of lifestyle-related diseases in Saudi Arabia.

PMID- 30202401
TI  - Frequency of use of non-prescribed medication among population sample from Al
      Madina City and its impact on quality of care in Saudi Arabia.
AB  - Objective: Self-medication can be defined as the practice of using drugs that
      have not been prescribed, recommended, or controlled by a certified health-care
      professional. This term can be used when discussing patients who use non
      prescription medications to treat self-diagnosed disorders or symptoms, without
      consulting a medical practitioner and without any medical supervision. The
      objectives of this study are to identify patterns of self-medication in Saudi
      Arabia, to measure the association between gender and the use of non-prescribed
      medication, and to identify the type of medications involved, the dosages used,
      and patient's sources of knowledge regarding the types, and doses of medications.
      Method: Cross-section analytical observational study, conducted in Al Medina
      city, Saudi Arabia, over 6 months using a pretested self-administered
      questionnaire using a convenience sampling technique. Results: With a response
      rate of 68.8%, it was found that 72.5% reported the use of non-prescribed
      medication and 24.3% reported a history of experiencing side effects from using
      non-prescribed medication with no significant difference between male and female.
      81% were keen to read the medication instruction with higher response among
      females.Analgesics were the most common type of medication used with an 86.5%
      agreement with no statistical significant differences between male and females.
      Conclusion: The study found heavy use of non-prescribed medication among the Al
      Medina residents sampled. This suggests a need for specialist training programs
      that could be directed at pharmacists, to help them disseminate information on
      the safe use of OTC or non-prescribed medications.

PMID- 30202398
TI  - Overexpression of the Drosophila ATR homologous checkpoint kinase Mei-41 induces
      a G2/M checkpoint in Drosophila imaginal tissue.
AB  - Background: DNA damage generally results in the activation of ATM/ATR kinases and
      the downstream checkpoint kinases Chk1/Chk2. In Drosophila melanogaster, the ATR
      homologue meiotic 41 (mei-41) is pivotal to DNA damage repair and cell cycle
      checkpoint signalling. Although various mei-41 mutant alleles have been analyzed
      in the past, no gain-of-function allele is yet available. To fill this gap, we
      have generated transgenic flies allowing temporal and tissue-specific induction
      of mei-41. Results: Overexpression of mei-41 in wing and eye anlagen affects
      proliferation and a G2/M checkpoint even in the absence of genomic stress.
      Similar consequences were observed following the overexpression of the downstream
      kinase Grapes (Grp) but not of Loki (Lok), encoding the respective Drosophila
      Chk1 and Chk2 homologues, in agreement with their previously reported activities.
      Moreover, we show that irradiation induced cell cycle arrest was prolonged in the
      presence of ectopic mei-41 expression. Similar to irradiation stress, mei-41
      triggered the occurrence of a slower migrating form of Grp, implying specific
      phosphorylation of Grp in response to either signal. Using a p53R-GFP biosensor,
      we further show that overexpression of mei-41 was sufficient to elicit a robust
      p53 activation in vivo. Conclusion: We conclude that overexpression of the
      Drosophila ATR homologue mei-41 elicits an effectual DNA damage response
      irrespective of irradiation.

PMID- 30202399
TI  - The effect of brief versus individually tailored dietary advice on change in
      diet, lipids and blood pressure in patients with inflammatory joint disease.
AB  - Background: Patients with inflammatory joint diseases (IJD) have an increased
      risk of cardiovascular disease (CVD) compared to the general population.
      Nutritional advice has been shown to influence CVD risk factors. Our objective
      was to evaluate whether an individually tailored dietary counselling versus a
      brief standardised advice on heart-friendly diet had comparable effect on change
      in diet, lipids and blood pressure (BP) in patients with IJD. Methods: Thirty-one
      patients with IJD aged 40-80 years received a brief standardised advice (4 min)
      on heart-friendly diet by a physician. Sixteen of the patients were randomised to
      receive an additional, individually tailored, heart-friendly dietary counselling
      session (60 min) by a dietitian. Change in dietary habits, measured by a
      validated questionnaire (SmartDiet), lipids, BP and C-reactive protein (CRP) were
      assessed after 8 weeks of follow-up. Results: After 8 weeks, the average increase
      in SmartDiet score was 5.1 and 5.7 points in the diet group (DG) and the control
      group (CG), respectively ( p = 0.65). Low-density lipoprotein cholesterol (LDL-c)
      was reduced by 12.6% in the DG versus 2.4% in the CG ( p = 0.05). There were no
      significant differences between the two groups regarding change in BP, lipids or
      CRP. Conclusion: Individually tailored dietary counselling resulted in more heart
      friendly food choices in patients with IJD. However, the change in SmartDiet
      score was comparable for IJD patients receiving a brief nutritional advice and
      individually tailored heart-friendly dietary counselling. Further studies
      evaluating the longitudinal effects of dietary advice on CVD outcome in patients
      with IJD are warranted.

PMID- 30202402
TI  - Safety of the plastibell circumcision in neonates, infants, and older children.
AB  - Objectives: The objectives of this study were to determine the safety of the
      Plastibell device (PD) circumcision in neonates, infants, and older children.
      Patients and Methods: A prospective, descriptive study was conducted in private
      clinics of district Poonch and district Sudhanuti Azad Kashmir, Pakistan, during
      the period from November 2014 to August 2017. Research was conducted in light of
      guidelines set by Helsinki declaration. Healthy male babies free of any clinical
      signs of illness and congenital anomaly were included in the study. The babies
      having weight <3 kg at the time of surgery were excluded from the study. The
      parents/guardian were explained about the procedure and informed consent was
      taken. The complications that developed postoperatively were recorded. The record
      of all cases was analyzed retrospectively for safety outcome and complications
      developed in neonates, infants, and older children. Results: A total of 1000
      cases including 655 (65.5%) neonates, 241 (24.1%) infants, and 104 (10.4%)
      children between 1 and 5 years of age were selected. The PD circumcision was done
      in all these cases. Of these, 93.5% neonates, 89.6% infants, and 66.3% children
      older than 1 years of age had no complications postoperatively. The complication
      rate was highest among the children between 1 and 5 years of age as compared to
      neonates and infants. The complications such as bleeding prepuce, hematoma, and
      swelling prepuce were higher in infants than neonates while superficial infection
      and buried glans were noted more in neonates than infants. Conclusion: It may be
      inferred from our findings that Plastibell circumcision is safer if done in the
      1st year of life and younger the age better is prognosis in healthy male babies.

PMID- 30202403
TI  - Oxidative stress markers and antioxidant activity in patients admitted to
      Intensive Care Unit with acute myocardial infarction.
AB  - Objectives: The aim of the study was to compare the levels of oxidative stress
      biomarkers and antioxidants in acute myocardial infarction (AMI) patients with
      healthy individuals and to investigate the effectiveness of these parameters as
      risk or illness indicators. Methodology: This study was conducted on AMI patients
      admitted to Intensive Care Unit of Al-Salam Hospital and Ibn-Sina Hospital in
      Mosul, Iraq. Considering inclusion and exclusion criteria, a total of 161
      patients and 156 healthy individuals in the age group of 30-80 years were
      selected for the study. The study groups were screened by estimating cardiac
      markers and electrocardiography (ECG). Results: The results indicated a
      significant increase in the level of serum malondialdehyde, peroxynitrite, and
      uric acid (P< 0.001). A minor increase in the serum ceruloplasmin level was
      observed in patients with AMI as compared to healthy individuals. The study also
      observed a significant decrease in the level of glutathione, Vitamin E, and
      Vitamin C (P< 0.001), with no significant difference in the level of Vitamin A in
      patients with AMI. Conclusion: The imbalance in the oxidative status and
      antioxidant activity in AMI patients reflects the importance of measuring the
      level of serum oxidative stress biomarkers and antioxidants as a diagnostic and
      prognostic tool for the medical management of AMI. Oxidative stress biomarkers
      and antioxidants might be good predictors or indicators for the risk of AMI.
      Oxidative stress markers contribute in the pathogenesis of AMI and excess of
      reactive oxygen species overwhelm the stability of the antioxidants.

PMID- 30202404
TI  - Profile and management outcomes of glaucoma cases at Qassim University Hospital.
AB  - Objective: In view of the paucity of community-based data about glaucoma in Saudi
      Arabia, better planning to address visual disabilities due to glaucoma is a
      challenge. Providing hospital-based data from semi-urban places will complement
      the picture based on information of tertiary eye hospitals of capital. Methods:
      This is one-armed cohort study. All patients attending glaucoma subspecialty unit
      at our university hospital during 2014-2015 were evaluated for their demographic
      details, ocular status at presentation, management modalities, and follow-up
      status of treated eyes. The qualified and absolute success rates (intraocular
      pressure <22 mmHg with/without medication) were estimated. The determinants of
      success were analyzed. Results: We assessed 219 eyes of 122 patients of glaucoma
      patients. Bilateral glaucoma was in 97 (79.7%) patients. Primary chronic angle
      closure glaucoma in 102 (46.6%) eyes and primary open angle glaucoma (POAG) in 56
      (25.6%) were the main types of glaucoma. More than half of the eyes with glaucoma
      had a normal functional vision, while 9.2% had vision <20/400. At presentation,
      133 (60.7%) had undergone surgical procedure including laser iridotomy. At last
      follow-up, 135 (62%) of glaucomatous eyes were not using glaucoma medications.
      The decline in a number of glaucoma medications at last follow-up compared to 1st
      visit was statistically significant (P < 0.001). Conclusions: At tertiary eye
      center of semi-urban area of Saudi Arabia had primary chronic angle-closure
      glaucoma (PCACG) as the main type of adult glaucoma. Vision does not seem to
      understand the severity of glaucoma at presentation. POAG cases were medically
      managed while PCACG cases were managed both with laser and surgeries.

PMID- 30202406
TI  - Applying filtration steps to interpret the results of whole-exome sequencing in a
      consanguineous population to achieve a high detection rate.
AB  - Objective: Interpreting whole-exome sequencing (WES) data are challenging,
      requiring extensive time, and effort to review all the variants in the variant
      call format. Here, we examined the application of custom filters to narrow the
      number of candidate variants in a consanguineous population that requires further
      analysis. Methods: In 100 cases undergoing WES, we applied a custom filtration
      process to look primarily for homozygous variants in autosomal recessive (AR)
      disorders, and second for variants in either autosomal dominant or x-linked
      disorders. Results: Most identified disease-causing variants were homozygous in
      AR disorders. By applying our custom filtration process, we narrowed the number
      of candidate variants requiring further analysis to 5-15 per case while
      maintaining a high detection rate and completing analysis in around 45 min.
      Conclusion: A custom filtration process and strategy targeting a specific
      population provide excellent detection rates in less time and should be
      considered as a first-tier laboratory workflow for analysis.

PMID- 30202405
TI  - The effects of audio stimuli on auditory-evoked potential in normal hearing Malay
      adults.
AB  - Objectives: The hearing process in the brain is very complicated and hard to
      solve. However, an understanding of the hearing process is an essential issue and
      needed in many rehabilitation or treatment applications. This study investigates
      and compares the effects of simple and complex sounds on latency and amplitude of
      various event-related potential (ERP) components to male ethnic Malay adults.
      Comparisons were made with previous studies. Materials and Methods: Simple and
      complex sounds were used (pure tones and the naturally produced Malay consonant
      vowels [CVs]) to evoke the cortical auditory-evoked potential (CAEP) signals.
      Moreover, this study analyzed the influence of related CAEP components that are
      distinct to the selected population and determined which of the ERP components
      among (CAEP) components is most affected by the two distinct stimuli. Moreover,
      the study used classification algorithms to discover the ability of the brain in
      distinguishing CAEP evoked by stimuli contrasts. Results: The results showed some
      resemblance between our results and ERP waveforms outlined in previous studies
      conducted on native speakers of English. On the other hand, it was also observed
      that the P1 and N2 had a significant effect in amplitude due to different
      stimulus. Conclusion: The results show high classification accuracy for the brain
      to distinguish auditory stimuli. Moreover, the results indicated some resemblance
      to previous studies conducted on native English speakers using similar tones and
      English CV stimuli. However, the amplitudes and latencies of the P1 were found to
      have a significant difference due to stimuli complexity.

PMID- 30202407
TI  - Effects of orally administered lactoferrin and lactoperoxidase on symptoms of the
      common cold.
AB  - Objectives: Lactoferrin (LF) and lactoperoxidase (LPO) are present in human
      saliva. LF has been demonstrated to show antibacterial and antiviral activities.
      In saliva, LPO catalyzes the hydrogen peroxide-dependent oxidation of thiocyanate
      to hypothiocyanite that exhibits antimicrobial and antiviral properties. A
      randomized, open-label, parallel-group clinical trial was conducted to examine
      the effectiveness of sucking tablets containing LF and LPO (LF+LPO) in
      alleviating symptoms of the common cold and/or influenza infection. Methods: A
      total of 407 subjects were randomized into two groups, treatment and non
      treatment groups, and each group was further classified into subgroups habitually
      wearing a face mask, washing their hands, or gargling. The common cold,
      influenza, and gastrointestinal symptoms were used to evaluate the effectiveness,
      and the incidence and duration of symptoms were statistically analyzed. Results:
      The incidence and duration of common cold, gastrointestinal symptoms, and
      influenza infection were not statistically different between treatment and non
      treatment groups. LF+LPO tablets were moderately effective in reducing the
      incidence and duration of common cold symptoms in the subgroup that did not
      gargle and especially to shorten significantly the duration of fever higher than
      38 degrees C in the subgroup that did not wear a face mask. Conclusion: The
      results suggested that the effect of ingestion of the tablet is not obvious in
      alleviating common cold symptoms but may be helpful when the subjects do not
      follow precautionary measures such as gargling and the use of a protective face
      mask.

PMID- 30202408
TI  - A randomized controlled trial to study the effect of gross myofascial release on
      mechanical neck pain referred to upper limb.
AB  - Objective: Mechanical neck pain (NP) with referred pain to upper limb is a common
      problem and often leads to functional impairment of common activities of daily
      living. The present study is undertaken to study and compare the effect of gross
      myofascial release (MFR) of upper limb and neck alone with conventional
      physiotherapy against only conventional treatment in subjects with mechanical NP
      referred to upper limb in terms of cervical endurance, pain, range of motion, and
      function. Methods: Design: This was a experimental study; a total of 40 subjects
      clinically diagnosed with mechanical NP along with referred pain between the age
      group of 20 and 50 years. Intervention: Control group was given conventional
      treatment of hot moist pack, TENS, and stretching and strengthening exercise, and
      experimental group was given gross MFR of the neck and upper limb in addition to
      conventional therapy. Treatment was given for 6 consecutive days. Outcome
      measures used were pressure biofeedback to measure cervical endurance, goniometer
      for cervical ROM, Northwick Park NP questionnaire, and disabilities of arm,
      shoulder, and hand questionnaire. Results: Statistically significant change was
      present for pain, cervical flexure endurance, ROM, and functional abilities with
      P < 0.05 for both the groups except for neck flexor endurance in control group.
      Conclusion: Gross MFR of upper limb and neck is an effective technique for
      subjects with mechanical NP and has a faster rate of improvement.

PMID- 30202409
TI  - Outcome of diaphyseal pediatric forearm fractures following non-surgical
      treatment in a Level I Trauma Center.
AB  - Objectives: Pediatric diaphyseal forearm fractures are common injuries of
      childhood. Conservative modality of treatments is usually preferred when they are
      possible. We identified factors that may affect closed reduction success or lead
      to redisplacement in forearm diaphyseal fractures in children. Methods: This was
      a retrospective study from a level I trauma center on patients up to 18 years of
      age who presented with forearm diaphyseal fractures from January 1, 2007, to
      December 31, 2015. Cases were obtained from medical records. Data were collected
      and confirmed by plain films and medical files. Results: We included 145 patients
      in this study. The majority (86.2%) were boys. Around 29% of trials of closed
      reduction failed, and the patients were subsequently treated surgically.
      Following trials of closed reduction, 82.4% of both bone cases were successfully
      reduced compared to 42.9% of radius shaft cases (P = 0.006). Redisplacement
      following non-surgical treatment in the first follow-up was found in 32% of both
      bone cases and 13.3% of radial shaft cases. All Galeazzi cases that were
      successfully treated with closed reduction presented with no redisplacement on
      follow-up. Conclusion: Immediate surgical management might be considered in older
      children, especially above 12 years of age since they have a higher failure rate
      of closed reduction than younger ones. Fracture site should be taken into account
      when following pediatric diaphyseal forearm fractures following conservative
      treatments as cases with both bone involvement have a high success rate of closed
      reduction and considerably high rate of redisplacement compared to others.

PMID- 30202410
TI  - Push-out bond strength of different types of mineral trioxide aggregate in root
      dentin.
AB  - Objective: The objective of this study was to measure the push-out bond strength
      of three types of mineral trioxide aggregate (MTA) materials in root dentin.
      Methods: The study was carried out at the College of Dentistry, Imam Abdulrahman
      Bin Faisal University from March 2014 to January 2015. Thirty extracted maxillary
      central incisors were selected, instrumented, irrigated, and randomly assigned
      into three groups (n = 10): Group 1 - Ortho MTA; Group 2 - MTA Angelus; and Group
      3 - ProRoot MTA. Materials were mixed following the manufacturers'
      recommendations and canals were filled. Teeth were stored in distilled water for
      6 months. The push-out bond strength was evaluated using 2-mm thick coronal root
      sections. The data were analyzed with one-way ANOVA and Tukey-Kramer multiple
      comparison tests statistically significant at P < 0.05. Results: The mean bond
      strength values were 68.69 +/- 29.63 MPa for Ortho MTA, 42.54 +/- 32.78 MPa for
      MTA Angelus, and 72.75 +/- 26.27 MPa for ProRoot MTA groups. There were no
      significant differences between the bond strengths of tested materials (P >
      0.05). Conclusion: Ortho MTA, MTA Angelus, and ProRoot MTA materials showed
      similar push-out bond strength values in root dentin.

PMID- 30202411
TI  - Cardiovascular outcomes and safety with antidiabetic drugs.
AB  - Type 2 diabetes is a debilitating disease that impacts the life expectancy,
      quality of life, and health of an individual. Cardiovascular disease (CVD) is a
      common diabetes-associated complication and a principal cause for death in
      diabetic patients. This review aims to investigate and summarize the effect of
      Type 2 diabetes mellitus (T2DM) medications on CVD issues. A comprehensive
      literature review mainly from level 1 evidence was performed. Thirty-seven
      articles were extracted from Google Scholar, ScienceDirect, ProQuest, and PubMed
      Database using a combination of keywords. The findings suggest that different
      glucose-lowering agents have been tested for their efficacy and safety in T2DM
      with CVD. Some of the recent trials such as the "United Kingdom Prospective
      Diabetes Study," "Empagliflozin (EMPA) Cardiovascular (CV) Outcome Event Trial in
      T2DM Patients-Removing Excess Glucose" (EMPA-REG OUTCOME), "Liraglutide Effect
      and Action in Diabetes: Evaluation of CV Outcome Results," and "Trial to Evaluate
      CV and Other Long-term Outcomes with Semaglutide in Subjects with Type 2
      Diabetes" (SUSTAIN6) have shed important light on this vital clinical concern,
      thus demonstrating a convincing effect of liraglutide, semaglutide, and EMPA on
      CVD outcomes, while metformin is thought to be the first-line optimal oral agent
      to manage Type 2 diabetics. Some classes of drugs demonstrate CV protection, some
      of them may be a result of a class effect, and some differences might be based on
      the population enrolled individually. Most of the trials failed to show a
      significant benefit with regard to mortality and morbidity in spite of intensive
      glycemic control. This study, therefore, enabled us to develop a guide of
      potential antidiabetic medication that can influence or promote CV health. Health
      professionals in future should weigh the CV risk against possible advantages
      while prescribing antidiabetic medications.

PMID- 30202412
TI  - An insight into gingival depigmentation techniques: The pros and cons.
AB  - Pigmentation of gingiva not just has an impact on esthetics but also creates
      psychological negativity. Although a wide array of depigmentation techniques are
      available to manage this condition, there is a scarcity of literature that guides
      clinicians to choose the most appropriate technique. Hence, the aim of this
      review is to evaluate the available depigmentation therapeutic modalities with an
      emphasis on their merits and demerits. The databases of MEDLINE and Cochrane
      databases of systematic reviews were searched to collect relevant scientific
      literature. Cryosurgery followed by lasers has been reported to be the superior
      techniques with better esthetic results and low rate of recurrence. However,
      further randomized controlled longitudinal studies are warranted to elaborate the
      efficiency and effectiveness of available techniques.

PMID- 30202413
TI  - Systematic review and meta-analysis on efficacy of cefixime for treating
      gonococcal infections.
AB  - Background: Neisseria gonorrhea is known to have developed a high level of
      resistance against different classes of antimicrobials. Patients with coagulation
      disorders where intramuscular injections are contraindicated, oral cefixime in
      combination therapy can be utilized as an alternative regimen. Cefixime in
      combination with another macrolide might be considered as an alternative
      treatment option. The aim of this systematic review is to assess the efficacy of
      400 mg cefixime against a range of comparator drugs. Methodology: Extensive
      literature search for randomized controlled trials was performed using Medline,
      Cochrane Registry of Controlled Trials, Embase, and Clinical trials registers.
      The trials assessed the efficacy of cefixime against a range of comparator drugs.
      Primary outcome of the study was the clinical resolution of signs and symptoms
      and negative culture at the end of follow-up period. Results: After screening for
      a total of 1184, only 8 studies were eligible for a meta-analysis. Risk ratio
      random effects model was used with a 95% confidence interval (CI). The pooled
      efficacy of Cefixime was at 97% at 95 CI 1.01 (0.98, 1.05). No statistically
      significant difference was found between oral cefixime and comparator drugs.
      Conclusion: A total of 11 studies were included following a review of 1184
      publications. 8 randomized controlled trials for 400 mg oral cefixime were
      included in meta-analysis. Despite a high grade of evidence, a high risk of bias
      was found among studies. Hence, more high quality randomized controlled trials on
      cefixime needs to be performed in future to guide the treatment of gonococcal
      infections.

PMID- 30202414
TI  - Testicular infarction in a patient with sickle cell anemia: A case report.
AB  - Sickle cell anemia is one of the common inherited hemoglobinopathy disorders. It
      affects patient quality of life through different types of complications. Brain,
      lung, kidney, spleen, and bone marrow commonly affected; however, testicular
      infarction is rarely happened. This is a 29-year-old Saudi male who is known for
      sickle cell disease (SCD). He presented with left scrotal pain and swelling for 1
      week which did not respond to antibiotic. Scrotal ultrasound showed swollen
      heterogeneous hypoechoic left testicle with no blood flow, suggesting testicular
      infarction. Despite medical treatment, the patient went for orchiectomy.
      Pathology revealed extensive testicular infarction. Up to our knowledge, this is
      the first case report of testicular infarction in SCD in Arab countries, and the
      sixth case reported worldwide. Early diagnosis and doing unnecessary surgical
      intervention still unavoidable as there is lack of information. We think writing
      the first case of testicular infarction in sickle cell patients with Arab
      haplotype is worthful and it will add to the literature.

PMID- 30202415
TI  - Corrigendum: Oral Administration of alpha-Asarone Promotes Functional Recovery in
      Rats With Spinal Cord Injury.
AB  - [This corrects the article DOI: 10.3389/fphar.2018.00445.].

PMID- 30202416
TI  - Retraction: First Report of Vibrio tubiashii Associated with a Massive Larval
      Mortality Event in a Commercial Hatchery of Scallop Argopecten purpuratus in
      Chile.
AB  - [This retracts the article DOI: 10.3389/fmicb.2016.01473.].

PMID- 30202417
TI  - WNT and NOTCH signaling pathways as activators for epidermal growth factor
      receptor in esophageal squamous cell carcinoma.
AB  - Background: Esophageal squamous cell carcinoma (ESCC) is the most common
      histological type of esophageal cancer, with a poor prognosis. Deregulation of
      WNT and NOTCH signaling pathways is important in ESCC progression, which can be
      due to either malfunction of their components or crosstalk with other pathways.
      Therefore, identification of new crosstalk between such pathways may be effective
      to introduce new strategies for targeted therapy of cancer. A correlation study
      was performed to assess the probable interaction between growth factor receptors
      and WNT/NOTCH pathways via the epidermal growth factor receptor (EGFR) and
      Musashi1 (MSI1), respectively. Methods: Levels of MSI1/EGFR mRNA expression in
      tumor tissues from 48 ESCC patients were compared to their corresponding normal
      tissues using real-time polymerase chain reaction. Results: There was a
      significant correlation between EGFR and MSI1 expression (p = 0.05). Moreover,
      there was a significant correlation between EGFR/MSI1 expression and grade of
      tumor differentiation (p = 0.02). Conclusion: This study confirms a direct
      correlation between MSI1 and EGFR and may support the important role of MSI1 in
      activation of EGFR through NOTCH/WNT pathways in ESCC.

PMID- 30202418
TI  - Lnc-DC regulates cellular turnover and the HBV-induced immune response by
      TLR9/STAT3 signaling in dendritic cells.
AB  - Background: Lnc-DC is a specific group of long non-coding (Lnc) RNAs in dendritic
      cells (DCs). Its function has been previously studied, and includes roles in
      dendritic cell differentiation and the progression of some diseases. In this
      study, we observed the critical role of Lnc-DC in regulating the differentiation,
      growth, and apoptosis of dendritic cells. Methods: We first isolated peripheral
      blood mononuclear cells to culture and induce into DCs, which were then co
      cultured with hepatitis B virus (HBV)-secreting HepG2.2.15 cells for the
      detection of changes in Lnc-DC. The expression levels of TLR9, p-STAT3, and SOCS3
      were tested with qPCR and western blot. MTT assays were used to analyze the cell
      proliferation, cell cycle, and apoptosis. We used ELISA to test the expression of
      TNF-alpha, IL-1beta, IL-6, IL-12p40, and IFN-gamma. Results: Co-culture with HBV
      secreting HepG2.2.15 cells increased the level of Lnc-DC and activated TLR9/STAT3
      signaling. The HBV DNA level (IU/ml) was positively correlated with levels of Lnc
      DC and TLR9, further demonstrating that Lnc-DC was associated with the immune
      response of HBV. Lnc-DC was shown to regulate TLR9/STAT3 signaling in dendritic
      cells. More interestingly, the regulation of Lnc-DC controlled the immune
      response by reducing the concentration of secreted TNF-alpha, IL-6, IL-12, and
      IFN-gamma, as well as increasing the IL-1beta concentration in dendritic cells.
      Conclusion: Lnc-DC is important in regulating the growth, apoptosis, and immune
      response of dendritic cells mediated by TLR9/STAT3 signaling, and was also
      activated by HBV. This study provides a previously unidentified mechanism
      underlying the immune response in dendritic cells.

PMID- 30202419
TI  - Age does not influence the disease course in a mouse model of Streptococcus
      pneumoniae serotype 3 meningitis.
AB  - In order to elucidate the causes for the increased mortality of aged patients
      with bacterial central nervous system (CNS) infections, we compared the course of
      Streptococcus pneumoniae (S. pneumoniae) meningitis in aged and young mice. Aged
      (21.2 +/- 3.1 months, n = 40) and young (3.2 +/- 0.9 months, n = 42) C57BL/6N and
      B6/SJL mice were infected by intracerebral injection of 50-70 CFU S. pneumoniae
      serotype 3 and monitored for 15 days. Aged and young mice did not differ
      concerning mortality (35% versus 38%), weight loss, development of clinical
      symptoms, bacterial concentrations in cerebellum and spleen as well as the number
      of leukocytes infiltrating the CNS. In contrast to results from our geriatric
      mouse model of Escherichia coli (E. coli) meningitis, where aged mice showed a
      higher mortality and an impaired elimination of bacteria, we did not find any
      differences between aged and young mice after intracerebral infection with S.
      pneumoniae serotype 3. This indicates that the increased susceptibility of aged
      mice to bacterial CNS infections is pathogen-specific: It appears less prominent
      in infections caused by hardly phagocytable pathogens with thick capsules like S.
      pneumoniae serotype 3, where the age-related decline of the phagocytic capacity
      of microglia and macrophages has a minor influence on the disease course.

PMID- 30202421
TI  - Protective effects of gamma-aminobutyric acid against H2O2-induced oxidative
      stress in RIN-m5F pancreatic cells.
AB  - Background: gamma-Aminobutyric acid (GABA) is a major inhibitory neurotransmitter
      in the central nervous system and reported to maintain the redox homeostasis and
      insulin secretion function of pancreatic beta cells. This study tested the
      hypothesis that GABA maintains cellular redox status, and modulates glycogen
      synthase kinase (GSK)-3beta and antioxidant-related nuclear factor erythroid 2
      related factor 2 (NRF2) nuclear mass ratio in the H2O2-injured RINm5F cells.
      Methods: RINm5F cells were treated with/without GABA (50, 100 and 200 MUmol/L)
      for 48 h and then exposed to 100 MUmol/L H2O2 for 30 min. Viable cells were
      harvested, and dichloro-dihydro-fluorescein diacetate (DCFH-DA) was used to
      detect reactive oxygen species (ROS) level; cellular redox status and insulin
      secretion were measured; cell viability was determined by 3-(4,5-dimethyl-thiazol
      2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay; mitochondrial membrane
      potential (MMP) was detected by flow cytometry; relative genes levels were
      analyzed by reverse transcriptase polymerase chain reaction (RT-PCR); western
      blotting was used to determine protein expression of GSK-3beta and p-GSK-3beta
      (Ser9), and nuclear and cytoplasmic NRF2. Results: H2O2 increased ROS production,
      and induced adverse affects in relation to antioxidant defense systems and
      insulin secretion. These changes were restored by treatment with 100 and 200
      MUmol/L GABA. In addition, 100 or 200 MUmol/L GABA induced membrane
      depolarization and increased cell viability. These effects were mediated by
      Caspase-3, Bcl-2 associated X protein (Bax) and B-cell lymphoma-2 (Bcl-2)
      expression. Western blotting indicated that GABA inhibited GSK-3beta by
      increasing p-GSK-3beta (Ser9) level, and directed the transcription factor NRF2
      to the nucleus. Conclusion: In rat insulin-producing RINm5F cells, GABA exerts
      its protective effect by regulating GSK-3beta and NRF2, which governs redox
      homeostasis by inhibiting apoptosis and abnormal insulin secretion by exposure to
      H2O2.

PMID- 30202420
TI  - The baseline levels and risk factors for high-sensitive C-reactive protein in
      Chinese healthy population.
AB  - Background: Recent studies show that C-reactive protein (CRP) is not only a
      biomarker but also a pathogenic mediator contributing to the development of
      inflammation and ageing-related diseases. However, serum levels of CRP in the
      healthy ageing population remained unclear, which was investigated in the present
      study. Methods: Serum levels of high sensitive C-reactive protein (hs-CRP),
      glucose (Glu), triglyceride (TG), cholesterol (CHOL), high-density lipoprotein
      cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), superoxide
      dismutase (SOD), serum creatinine (SCr), serum uric acid (SUA) were measured in
      6060healthy subjects (3672 male and 2388 female, mean age:45.9 years) who
      received routine physical examination at Sun Yat-sen Memorial Hospital,
      Guangzhou, China. Results: In total of 6060 healthy people, serum levels of hs
      CRP were significantly increased with ageing (P < 0.05), particularly in those
      with age over 45-year-old (1.31[0.69-2.75] vs 1.05[0.53-2.16]mg/L, P < 0.001).
      Interestingly, levels of serum hs-CRP were significantly higher in male than
      female population (1.24[0.65-2.57] vs 1.07[0.53-2.29]mg/L, P < 0.001).
      Correlation analysis also revealed that serum levels of hs-CRP positively
      correlated with age and SUA, but inversely correlated with serum levels of HDL-c
      and SOD (all P < 0.05). Conclusions: Baseline levels of serum hs-CRP are
      increased with ageing and are significantly higher in male than female healthy
      population. In addition, elevated serum levels of hs-CRP are also associated with
      increased SUA but decreased HDL-c and SOD. Thus, serum levels of hs-CRP may be an
      indicator associated with ageing in healthy Chinese population.

PMID- 30202424
TI  - Donor milk intake and infant growth in a South African neonatal unit: a cohort
      study.
AB  - Background: Implications of donor milk feedings on infant growth in resource
      limited settings remain uncertain. This knowledge gap includes the impact of
      donor milk availability on infant intake of mother's own milk. Therefore, this
      investigation aimed to measure intake and growth in infants receiving donor milk
      when born to women from resource limited backgrounds with high rates of human
      immunodeficiency virus (HIV). Methods: A retrospective cohort study enrolled
      eligible infants admitted to a South African combined neonatal intensive and
      secondary high care unit, within a one year admission period during 2015, with
      signed consent for donor milk feedings. A certified milk bank provided donor
      milk. Daily nutritional intake during the first month was recorded. Details
      included proportional intake of donor milk, mother's own milk and infant formula.
      The primary outcome of infant growth velocity from day back to birth weight to
      discharge was calculated when length of stay was >=14 days. Analyses primarily
      used T-tests; mixed effects models compared weekly calorie intake. Results: One
      hundred five infants with donor milk consent were born at 30.9 +/- 3.6 weeks of
      gestation, weighing 1389 +/- 708 g. Forty percent of mothers had HIV. Infant
      growth velocity did not differ based on percent of feedings as donor milk (>=
      50%: 11.8 +/- 4.9 g/kg/d; < 50%: 13.5 +/- 5.3 g/kg/d; p = 0.3). Percent of
      feedings from donor milk was similar based on maternal HIV status (positive: 31
      +/- 25%; negative: 36 +/- 29%; p = 0.4), as was percent of feedings as mother's
      milk (positive: 53 +/- 35%; negative: 58 +/- 30%; p = 0.4). Calorie intake
      increased markedly during the first two weeks and then plateaued (p < 0.0001).
      Conclusions: Donor milk feedings in higher proportions did not further impair
      growth of infants managed in a South African combined neonatal intensive and
      secondary high care unit with growth rates already below reference ranges. The
      provision of donor milk contributed to feedings being composed of primarily human
      milk during the first month. Increasing early calorie intake may improve infant
      growth in this center.

PMID- 30202423
TI  - Work related injuries in Qatar: a framework for prevention and control.
AB  - Work related injuries (WRIs) are a growing public health concern that remains
      under-recognized, inadequately addressed and largely unmeasured in low and middle
      income countries (LMIC's). However, even in high-income countries, such as those
      in Gulf Cooperating Council (GCC) like Qatar, there are challenges in assuring
      the health and safety of its labor population. Countries in the GCC have been
      rapidly developing as a result of the economic boom from the petrochemical
      industry during the early seventies. Economic prosperity has propelled the
      migration of workers from less developed countries to make up for the human
      resource deficiency to develop its infrastructure, service and hospitality
      industries. Although these countries have gradually made huge gains in health,
      economy and human development index, including improvements in life expectancy,
      education, and standard of living, there remains a high incidence of work-related
      injuries especially in jobs in the construction and petrochemical sector.
      Currently, there is scarcity of literature on work-related injuries, especially
      empirical studies documenting the burden, characteristics and risk factors of
      work injuries and the work injured population, which includes large numbers of
      migrant workers in many GCC countries. This paper will focus on the current
      understanding of WRIs in those countries and identify the gaps in current
      approaches to workplace injury prevention, outlining current status of WRI
      prevention efforts in Qatar, and propose a framework of concerted action by multi
      sectoral engagement.

PMID- 30202425
TI  - Investigating factors associated with success of breastfeeding in first-time
      mothers undergoing epidural analgesia: a prospective cohort study.
AB  - Background: We investigated the possible risk factors that could influence the
      likelihood of breastfeeding at 5 to 9 weeks postpartum with our primary aim being
      to analyse the associations between psychological vulnerabilities, such as
      peripartum depression and anxiety, and continued breastfeeding. Our secondary aim
      was to investigate other non-psychological factors' influence on continued
      breastfeeding. Methods: A prospective cohort study was conducted in KK Women's
      and Children's Hospital in Singapore. Healthy nulliparous parturients at >=36
      weeks gestation with a singleton fetus who received epidural analgesia were
      recruited. Demographic and anaesthetic data were obtained. Self-reported
      psychological and pain determinants such as anxiety (State-Trait Anxiety
      Inventory), depression (Edinburgh Postnatal Depression Scale), stress (Perceived
      Stress Scale), pain susceptibility (Pain Catastrophizing Scale) and pain
      perception (McGill Pain Questionnaire) were also recorded at baseline. A phone
      interview was then performed at 5 to 9 weeks postpartum to obtain information on
      breastfeeding status. Results: 329 participants were included into this study, of
      which 263 (79.9%) of them were still breastfeeding at 5 weeks postpartum.
      Multivariate logistic regression analysis showed that a higher State-Trait
      Anxiety Inventory score (Adjusted Odds Ratio [AOR] 0.97; 95% Confidence Interval
      [CI] 0.94, 1.00) at baseline, higher intrapartum blood loss (AOR 0.76; 95% CI
      0.61, 0.93), and occurrence of fetal anomalies (AOR 0.15; 95% CI 0.03, 0.72) were
      associated with reduced likelihood of breastfeeding at 5 to 9 weeks postpartum.
      Indians (AOR 0.56; 95% CI 0.20, 1.53), Malays (AOR 0.30; 95% CI 0.14, 0.62) and
      other ethnicities (AOR 0.36; 95% CI 0.16, 0.83) were less likely to continue
      breastfeeding compared to Chinese participants. On the other hand, receiving any
      support services on breastfeeding during the participants' hospital stay was 3.3
      times more likely (AOR 3.30; 95% CI 1.21, 9.02) to increase the likelihood of
      breastfeeding at 5 to 9 weeks postpartum. Conclusion: We identified 5 independent
      association factors that could have significant influences on breastfeeding at 5
      to 9 weeks postpartum. Healthcare providers could utilize this risk
      stratification to identify parturients likely to have poorer breastfeeding
      outcomes and undertake interventions that may help safeguard optimization of
      breastfeeding outcomes and parturient care. Trial registration:
      Clinicaltrials.gov NCT02278601. Registered 26 October 2014.

PMID- 30202426
TI  - Use of a temporary immersion bioreactor system for the sustainable production of
      thapsigargin in shoot cultures of Thapsia garganica.
AB  - Background: Thapsigargin and nortrilobolide are sesquiterpene lactones found in
      the Mediterranean plant Thapsia garganica L. Thapsigargin is a potent inhibitor
      of the sarco/endoplasmic reticulum calcium ATPase pump, inducing apoptosis in
      mammalian cells. This mechanism has been used to develop a thapsigargin-based
      cancer drug first by GenSpera and later Inspyr Therapeutics (Westlake Village,
      California). However, a stable production of thapsigargin is not established.
      Results: In vitro regeneration from leaf explants, shoot multiplication and
      rooting of T. garganica was obtained along with the production of thapsigargins
      in temporary immersion bioreactors (TIBs). Thapsigargin production was enhanced
      using reduced nutrient supply in combination with methyl jasmonate elicitation
      treatments. Shoots grown in vitro were able to produce 0.34% and 2.1% dry weight
      of thapsigargin and nortrilobolide, respectively, while leaves and stems of wild
      T. garganica plants contain only between 0.1 and 0.5% of thapsigargin and below
      detectable levels of nortrilobolide. In addition, a real-time reverse
      transcription PCR (qRT-PCR) study was performed to study the regulatory role of
      the biosynthetic genes HMG-CoA reductase (HMGR), farnesyl diphosphate synthase
      (FPPS), epikunzeaol synthase (TgTPS2) and the cytochrome P450 (TgCYP76AE2) of
      stem, leaf and callus tissues. Nadi staining showed that the thapsigargins are
      located in secretory ducts within these tissues. Conclusions: Shoot regeneration,
      rooting and biomass growth from leaf explants of T. garganica were achieved,
      together with a high yield in vitro production of thapsigargin in TIBs.

PMID- 30202422
TI  - Olfactory dysfunction revisited: a reappraisal of work-related olfactory
      dysfunction caused by chemicals.
AB  - Occupational exposure to numerous individual chemicals has been associated with
      olfactory dysfunction, mainly in individual case descriptions. Comprehensive
      epidemiological investigations into the olfactotoxic effect of working substances
      show that the human sense of smell may be impaired by exposure to metal compounds
      involving cadmium, chromium and nickel, and to formaldehyde. This conclusion is
      supported by the results of animal experiments. The level of evidence for a
      relationship between olfactory dysfunction and workplace exposure to other
      substances is relatively weak.

PMID- 30202429
TI  - Implementation and adoption of advanced care planning in the elderly trauma
      patient.
AB  - Background: Geriatric trauma has high morbidity and mortality, often requiring
      extensive hospital stays and interventions. The number of geriatric trauma
      patients is also increasing significantly and accounts for a large proportion of
      trauma care. Specific geriatric trauma protocols exist to improve care for this
      complex patient population, who often have various comorbidities, pre-existing
      medications, and extensive injury within a trauma perspective. These guidelines
      for geriatric trauma care often suggest early advanced care planning (ACP)
      discussions and documentation to guide patient and family-centered care. Methods:
      A provincial ACP program was implemented in April of 2012, which has since been
      used by our level 1 trauma center. We applied a before and after study design to
      assess the documentation of goals of care in elderly trauma patients following
      implementation of the standardized provincial ACP tool on April 1, 2012. Results:
      Documentation of ACP in elderly major trauma patients following the
      implementation of this tool increased significantly from 16 to 35%. Additionally,
      secondary outcomes demonstrated that many more patients received goals of care
      documentation within 24 h of admission, and 93% of patients had goals of care
      documented prior to intensive care unit (ICU) admission. The number of trauma
      patients that were admitted to the ICU also decreased from 17 to 5%. Conclusion:
      Early advanced care planning is crucial for geriatric trauma patients to improve
      patient and family-centered care. Here, we have outlined our approach with modest
      improvements in goals of care documentation for our geriatric population at a
      level 1 trauma center. We also outline the benefits and drawbacks of this
      approach and identify the areas for improvement to support improved patient
      centered care for the injured geriatric patient. Here, we have provided a
      framework for others to implement and further develop.

PMID- 30202428
TI  - The long-term outcomes of early abdominal wall reconstruction by bilateral
      anterior rectus abdominis sheath turnover flap method in critically ill patients
      requiring open abdomen.
AB  - Background: In a previous study, we reported the usefulness of early abdominal
      wall reconstruction using bilateral anterior rectus abdominis sheath turnover
      flap method (turnover flap method) in open abdomen (OA) patients in whom early
      primary fascial closure was difficult to achieve. However, the long-term outcomes
      have not been elucidated. In the present study, we aimed to evaluate the
      procedure, particularly in terms of ventral hernia, pain, and daily activities.
      Methods: Between 2001 and 2013, 15 consecutive patients requiring OA after
      emergency laparotomy and in whom turnover flap method was applied were
      retrospectively identified. The long-term outcomes were evaluated based on
      medical records, physical examinations, CT imaging, and a ventral hernia pain
      questionnaire (VHPQ). Results: The turnover flap method was applied in 2 trauma
      and 13 non-trauma patients.In most of cases, primary fascial closure could not be
      achieved due to massive visceral edema. The turnover flap method was performed
      for abdominal wall reconstruction at the end of OA. The median duration of OA was
      6 (range 1-42) days. One of the 15 patients died of multiple organ failure during
      initial hospitalization after the performance of the turnover flap method.
      Fourteen patients survived, and although wound infection was observed in 3
      patients, none showed enteric fistula, abdominal abscess, graft infection, or
      ventral hernia during hospitalization. However, it was found that 1 patient
      developed ventral hernia during follow-up at an outpatient visit. Nine of 14
      patients were alive and able to be evaluated with a VHPQ (follow-up period:
      median 10 years; range 3-15 years). Seven out of nine patients were satisfied
      with this procedure, and none complained of pain or were limited in their daily
      activities. Conclusions: Based on the results of this study, early abdominal
      reconstruction using the turnover flap method can be considered to be safe and
      effective as an alternative technique for OA patients in whom primary fascial
      closure is considered difficult to achieve.

PMID- 30202427
TI  - Measuring DNA content in live cells by fluorescence microscopy.
AB  - Background: Live-cell fluorescence microscopy (LCFM) is a powerful tool used to
      investigate cellular dynamics in real time. However, the capacity to
      simultaneously measure DNA content in cells being tracked over time remains
      challenged by dye-associated toxicities. The ability to measure DNA content in
      single cells by means of LCFM would allow cellular stage and ploidy to be coupled
      with a variety of imaging directed analyses. Here we describe a widely applicable
      nontoxic approach for measuring DNA content in live cells by fluorescence
      microscopy. This method relies on introducing a live-cell membrane-permeant DNA
      fluorophore, such as Hoechst 33342, into the culture medium of cells at the end
      of any live-cell imaging experiment and measuring each cell's integrated nuclear
      fluorescence to quantify DNA content. Importantly, our method overcomes the
      toxicity and induction of DNA damage typically caused by live-cell dyes through
      strategic timing of adding the dye to the cultures; allowing unperturbed cells to
      be imaged for any interval of time before quantifying their DNA content. We
      assess the performance of our method empirically and discuss adaptations that can
      be implemented using this technique. Results: Presented in conjunction with cells
      expressing a histone 2B-GFP fusion protein (H2B-GFP), we demonstrated how this
      method enabled chromosomal segregation errors to be tracked in cells as they
      progressed through cellular division that were later identified as either diploid
      or polyploid. We also describe and provide an automated Matlab-derived algorithm
      that measures the integrated nuclear fluorescence in each cell and subsequently
      plots these measurements into a cell cycle histogram for each frame imaged. The
      algorithm's accurate assessment of DNA content was validated by parallel flow
      cytometric studies. Conclusions: This method allows the examination of single
      cell dynamics to be correlated with cellular stage and ploidy in a high
      throughput fashion. The approach is suitable for any standard epifluorescence
      microscope equipped with a stable illumination source and either a stage-top
      incubator or an enclosed live-cell incubation chamber. Collectively, we
      anticipate that this method will allow high-resolution microscopic analysis of
      cellular processes involving cell cycle progression, such as checkpoint
      activation, DNA replication, and cellular division.

PMID- 30202430
TI  - L-carnosine as an enhancer to computerized cognitive behaviour therapy in
      Japanese workers, an unjustified claim.
AB  - This letter comments on the conclusion drawn by Shirotsuki et al. (2017) in their
      article entitled "The effect for Japanese workers of a self-help computerized
      cognitive behaviour therapy program with a supplement soft drink", recently
      published in BioPsychoSocial Medicine. The authors concluded that their drink,
      containing L-carnosine, enhances the effects of a computerized cognitive
      behavioural therapy (CCBT) on the psychological well-being of healthy Japanese
      workers. Yet, we argue that their conclusion is unfounded given their results and
      the methodological shortcomings of their study. Briefly, while the authors
      reported improvement on the tension-anxiety subscale of the Profile of Mood
      States (POMS) in the CCBT only group, they also observed a lack of improvement on
      this subscale in the CCBT+L-carnosine group suggesting that the drink washes out
      this beneficial effect of CCBT. Methodological issues include the uncontrolled
      levels of L-carnosine metabolized by participants jeopardize the study's internal
      validity. Also, the clinical meaningfulness of the findings seems dubious as post
      treatment scores remained within the range of the general Japanese population.
      Consequently, we argue that Shirotsuki et al.'s study should be re-conducted
      before drawing any valid conclusion.

PMID- 30202431
TI  - "I prefer dying fast than dying slowly", how institutional abuse worsens the
      mental health of stranded Syrian, Afghan and Congolese migrants on Lesbos island
      following the implementation of EU-Turkey deal.
AB  - Background: In 2015 and early 2016, close to 1 million migrants transited through
      Greece, on their way to Western Europe. In early 2016, the closure of the "Balkan
      route" and the EU/Turkey-deal led to a drastic reduction in the flow of migrants
      arriving to the Greek islands. The islands became open detention centers, where
      people would spend months or years under the constant fear of being returned to
      Turkey.Syrians were generally granted refugee status in Greece and those arrived
      before the 20th of March 2016 had the option of being relocated to other European
      countries. Afghans had some chances of being granted asylum in Greece, whilst
      most migrants from the Democratic Republic of Congo were refused asylum.In a
      clinic run by Medecins sans Frontieres on Lesbos Island, psychologists observed a
      deterioration of the migrant's mental health (MH) since March 2016. In order to
      understand the MH needs for this stranded population it was essential to explore
      how, and by what factors, their mental health (MH) has been affected on Lesbos
      Island due to the EU/Turkey-deal. Methods: This was a qualitative study in which
      eight service providers' interviews and 12 focus group discussions with male and
      female Syrian, Afghan and Congolese migrants in two refugee camps on Lesbos
      Island. Thematic-content analysis was manually applied and triangulation of
      findings was undertaken to enhance the interpretation of data. Results: Three
      main themes were generated: 1) Institutional abuse, 2) Continuous traumatic
      stress (CTS) and 3) MH service provision. Institutional abuse was expressed by
      inhumane living conditions, lack of information in order to make future
      decisions, humiliation and depersonalization. This led to CTS that was expressed
      through being in a state of permanent emergency under lack of protective
      measures. Delays in appointments, lack of psychiatric care and differences in MH
      perceptions amongst migrants highlighted the provision of MH services.
      Conclusion: The EU/Turkey-deal reduced migrant flows at a very high price.
      Decongestion of the camps and the elimination of institutional abuse is urgently
      needed to reduce CTS and improve migrants' MH.

PMID- 30202432
TI  - Bio-hybrid inorganic microparticles derived from CO2 for highly efficient and
      selective removal of antibiotics.
AB  - Background: Antibiotics, which are the most important medication in human
      history, have brought global concerns due to their potential risk to human health
      and environment by accelerating the development of drug-resistant bacteria, and
      accumulating in the food chain system. Among antibiotics, oxytetracycline (OTC)
      is widely used in aquaculture, and its potential risk of toxicity to human by
      bioaccumulation has been reported. Therefore, the effective removal of OTC is
      highly needed. Results: In this study, we report bio-hybrid inorganic
      microparticles (apt-mag-SiCC) for efficient capturing and facile magnet-based
      separation of oxytetracycline (OTC). These bio-hybrid inorganic microparticles
      are composed of magnetic separable silica coated calcium carbonate microparticles
      (mag-SiCC) derived from CO2, conjugated with oxytetracycline binding aptamers
      (OBA). These bio-hybrid inorganic microparticles were successfully synthesized,
      based on the characterization data obtained by SEM, FT-IR, EDAX, BET, and CLSM.
      About 6 MUm sized bio-hybrid inorganic microparticles showed low non-specific
      adsorption to OTC and other molecules, and the selective capturing towards to the
      OTC in both buffer and tap water. Moreover, these bio-hybrid mineral
      microparticles were found to be stable, even after the repeated usages,
      maintaining the initial capturing efficiency. Conclusion: Using the newly
      synthesized bio-hybrid inorganic microparticles, we could successfully capture
      OTC by facile magnet-based separation. With advantages of theses bio-hybrid
      inorganic microparticles such as easy fabrication, low-price, and environmental
      friendliness, this novel material could be utilized in the drinking water
      treatment, in vitro medicinal diagnostics, or in vitro removal of antibiotics
      lining out from the blood (blood purification).

PMID- 30202433
TI  - Addition of beta-galactosidase boosts the xyloglucan degradation capability of
      endoglucanase Cel9D from Clostridium thermocellum.
AB  - Background: Increasing the efficiency of enzymatic biomass degradation is crucial
      for a more economically feasible conversion of abundantly available plant
      feedstock. Synergistic effects between the enzymes deployed in the hydrolysis of
      various hemicelluloses have been demonstrated, which can reduce process costs by
      lowering the amount of enzyme required for the reaction. Xyloglucan is the only
      major hemicellulose for which no such effects have been described yet. Results:
      We report the beneficial combination of two enzymes for the degradation of the
      hemicellulose xyloglucan. The addition of beta-galactosidase Bga2B from
      Clostridium stercorarium to an in vitro hydrolysis reaction of a model xyloglucan
      substrate increased the enzymatic efficiency of endoglucanase Cel9D from
      Clostridium thermocellum to up to 22-fold. Furthermore, the total amount of
      enzyme required for high hydrolysis yields was lowered by nearly 80%. Increased
      yields were also observed when using a natural complex substrate-tamarind kernel
      powder. Conclusion: The findings of this study may improve the valorization of
      feedstocks containing high-xyloglucan amounts. The combination of the
      endoglucanase Cel9D and the beta-galactosidase Bga2B can be used to efficiently
      produce the heptasaccharide XXXG. The exploitation of one specific
      oligosaccharide may open up possibilities for the use as a prebiotic or platform
      chemical in additional reactions.

PMID- 30202434
TI  - Engineering the fatty acid synthesis pathway in Synechococcus elongatus PCC 7942
      improves omega-3 fatty acid production.
AB  - Background: The microbial production of fatty acids has received great attention
      in the last few years as feedstock for the production of renewable energy. The
      main advantage of using cyanobacteria over other organisms is their ability to
      capture energy from sunlight and to transform CO2 into products of interest by
      photosynthesis, such as fatty acids. Fatty acid synthesis is a ubiquitous and
      well-characterized pathway in most bacteria. However, the activity of the enzymes
      involved in this pathway in cyanobacteria remains poorly explored. Results: To
      characterize the function of some enzymes involved in the saturated fatty acid
      synthesis in cyanobacteria, we genetically engineered Synechococcus elongatus PCC
      7942 by overexpressing or deleting genes encoding enzymes of the fatty acid
      synthase system and tested the lipid profile of the mutants. These modifications
      were in turn used to improve alpha-linolenic acid production in this
      cyanobacterium. The mutant resulting from fabF overexpression and fadD deletion,
      combined with the overexpression of desA and desB desaturase genes from
      Synechococcus sp. PCC 7002, produced the highest levels of this omega-3 fatty
      acid. Conclusions: The fatty acid composition of S. elongatus PCC 7942 can be
      significantly modified by genetically engineering the expression of genes coding
      for the enzymes involved in the first reactions of fatty acid synthesis pathway.
      Variations in fatty acid composition of S. elongatus PCC 7942 mutants did not
      follow the pattern observed in Escherichia coli derivatives. Some of these
      modifications can be used to improve omega-3 fatty acid production. This work
      provides new insights into the saturated fatty acid synthesis pathway and new
      strategies that might be used to manipulate the fatty acid content of
      cyanobacteria.

PMID- 30202435
TI  - Bacterial conversion of depolymerized Kraft lignin.
AB  - Background: Lignin is a potential feedstock for microbial conversion into various
      chemicals. However, the degradation rate of native or technical lignin is low,
      and depolymerization is needed to obtain reasonable conversion rates. In the
      current study, base-catalyzed depolymerization-using NaOH (5 wt%)-of softwood
      Kraft lignin was conducted in a continuous-flow reactor system at temperatures in
      the range 190-240  degrees C and residence times of 1 or 2 min. The ability of
      growth of nine bacterial strains belonging to the genera Pseudomonas and
      Rhodococcus was tested using the alkaline-treated lignin as a sole carbon source.
      Results: Pseudomonas fluorescens and Rhodococcus opacus showed the best growth of
      the tested species on plates with lignin. Further evaluation of P. fluorescens
      and R. opacus was made in liquid cultivations with depolymerized lignin (DL) at a
      concentration of 1 g/L. Size exclusion chromatography (SEC) showed that R. opacus
      consumed most of the available lower molecular weight compounds (approximately
      0.1-0.4 kDa) in the DL, but the weight distribution of larger fractions was
      almost unaffected. Importantly, the consumed compounds included guaiacol-one of
      the main monomers in the DL. SEC analysis of P. fluorescens culture broth, in
      contrast, did not show a large conversion of low molecular weight compounds, and
      guaiacol remained unconsumed. However, a significant shift in molecular weight
      distribution towards lower average weights was seen. Conclusions: Rhodococcus
      opacus and P. fluorescens were identified as two potential microbial candidates
      for the conversion/consumption of base-catalyzed depolymerized lignin, acting on
      low and high molecular weight lignin fragments, respectively. These findings will
      be of relevance for designing bioconversion of softwood Kraft lignin.

PMID- 30202436
TI  - Advances in metabolic modeling of oleaginous microalgae.
AB  - Production of biofuels and bioenergy precursors by phototrophic microorganisms,
      such as microalgae and cyanobacteria, is a promising alternative to conventional
      fuels obtained from non-renewable resources. Several species of microalgae have
      been investigated as potential candidates for the production of biofuels, for the
      most part due to their exceptional metabolic capability to accumulate large
      quantities of lipids. Constraint-based modeling, a systems biology approach that
      accurately predicts the metabolic phenotype of phototrophs, has been deployed to
      identify suitable culture conditions as well as to explore genetic enhancement
      strategies for bioproduction. Core metabolic models were employed to gain insight
      into the central carbon metabolism in photosynthetic microorganisms. More
      recently, comprehensive genome-scale models, including organelle-specific
      information at high resolution, have been developed to gain new insight into the
      metabolism of phototrophic cell factories. Here, we review the current state of
      the art of constraint-based modeling and computational method development and
      discuss how advanced models led to increased prediction accuracy and thus
      improved lipid production in microalgae.

PMID- 30202437
TI  - Expressing the Thermoanaerobacterium saccharolyticum pforA in engineered
      Clostridium thermocellum improves ethanol production.
AB  - Background: Clostridium thermocellum has been the subject of multiple metabolic
      engineering strategies to improve its ability to ferment cellulose to ethanol,
      with varying degrees of success. For ethanol production in C. thermocellum, the
      conversion of pyruvate to acetyl-CoA is catalyzed primarily by the pyruvate
      ferredoxin oxidoreductase (PFOR) pathway. Thermoanaerobacterium saccharolyticum,
      which was previously engineered to produce ethanol of high yield (> 80%) and
      titer (70 g/L), also uses a pyruvate ferredoxin oxidoreductase, pforA, for
      ethanol production. Results: Here, we introduced the T. saccharolyticum pforA and
      ferredoxin into C. thermocellum. The introduction of pforA resulted in
      significant improvements to ethanol yield and titer in C. thermocellum grown on
      50 g/L of cellobiose, but only when four other T. saccharolyticum genes (adhA,
      nfnA, nfnB, and adhEG544D ) were also present. T. saccharolyticum ferredoxin did
      not have any observable impact on ethanol production. The improvement to ethanol
      production was sustained even when all annotated native C. thermocellum pfor
      genes were deleted. On high cellulose concentrations, the maximum ethanol titer
      achieved by this engineered C. thermocellum strain from 100 g/L Avicel was 25
      g/L, compared to 22 g/L for the reference strain, LL1319 (adhA(Tsc)-nfnAB(Tsc)
      adhEG544D (Tsc)) under similar conditions. In addition, we also observed that
      deletion of the C. thermocellum pfor4 results in a significant decrease in
      isobutanol production. Conclusions: Here, we demonstrate that the pforA gene can
      improve ethanol production in C. thermocellum as part of the T. saccharolyticum
      pyruvate-to-ethanol pathway. In our previous strain, high-yield (~ 75% of
      theoretical) ethanol production could be achieved with at most 20 g/L substrate.
      In this strain, high-yield ethanol production can be achieved up to 50 g/L
      substrate. Furthermore, the introduction of pforA increased the maximum titer by
      14%.

PMID- 30202440
TI  - The diversity of hydrogen-producing bacteria and methanogens within an in situ
      coal seam.
AB  - Background: Biogenic and biogenic-thermogenic coalbed methane (CBM) are important
      energy reserves for unconventional natural gas. Thus, to investigate biogenic gas
      formation mechanisms, a series of fresh coal samples from several representative
      areas of China were analyzed to detect hydrogen-producing bacteria and
      methanogens in an in situ coal seam. Complete microbial DNA sequences were
      extracted from enrichment cultures grown on coal using the Miseq high-throughput
      sequencing technique to study the diversity of microbial communities. The species
      present and differences between the dominant hydrogen-producing bacteria and
      methanogens in the coal seam are then considered based on environmental factors.
      Results: Sequences in the Archaea domain were classified into four phyla and
      included members from Euryarchaeota, Thaumarchaeota, Woesearchaeota, and
      Pacearchaeota. The Bacteria domain included members of the phyla: Firmicutes,
      Proteobacteria, Bacteroidetes, Actinobacteria, Acidobacteria, Verrucomicrobia,
      Planctomycetes, Chloroflexi, and Nitrospirae. The hydrogen-producing bacteria was
      dominated by the genera: Clostridium, Enterobacter, Klebsiella, Citrobacter, and
      Bacillus; the methanogens included the genera: Methanorix, Methanosarcina,
      Methanoculleus, Methanobrevibacter, Methanobacterium, Methanofollis, and
      Methanomassiliicoccus. Conclusion: Traces of hydrogen-producing bacteria and
      methanogens were detected in both biogenic and non-biogenic CBM areas. The
      diversity and abundance of bacteria in the biogenic CBM areas are relatively
      higher than in the areas without biogenic CBM. The community structure and
      distribution characteristics depend on coal rank, trace metal elements,
      temperature, depth and groundwater dynamic conditions. Biogenic gas was mainly
      composed of hydrogen and methane, the difference and diversity were caused by
      microbe-specific fermentation of substrates; as well as by the environmental
      conditions. This discovery is a significant contribution to extreme microbiology,
      and thus lays the foundation for research on biogenic CBM.

PMID- 30202441
TI  - Rheological properties of corn stover slurries during fermentation by Clostridium
      thermocellum.
AB  - Background: Milling during fermentation, termed cotreatment, has recently been
      proposed as an alternative to thermochemical pretreatment as a means to increase
      the accessibility of lignocellulosic biomass to biological attack. A central
      premise of this approach is that partial solubilization of biomass changes the
      slurry's physical properties such that milling becomes more impactful and more
      feasible. A key uncertainty is the energy required to mill partially fermented
      biomass. To inform both of these issues, we report rheological characterization
      of small-particle, corn stover slurries undergoing fermentation by Clostridium
      thermocellum. Results: Fermented and unfermented corn stover slurries were found
      to be shear-thinning and well described by a power law model with an exponent of
      0.10. Plastic viscosity of a slurry, initially at 16 wt.% insoluble solids,
      decreased as a result of fermentation by a factor of 2000, with the first
      eightfold reduction occurring in the first 10% of carbohydrate conversion. Large
      amplitude oscillatory shear experiments revealed only minor changes to the
      slurry's rheological fingerprint as a result of fermentation, with the notable
      change being a reduction in the critical strain amplitude needed for the onset of
      nonlinearity. All slurries were found to be elastoviscoplastic, with the
      elastic/viscous crossover at roughly 100% strain amplitude. Conclusions: Whereas
      prior biomass rheology studies have involved pretreated feedstocks and
      solubilization mediated by fungal cellulase, we report results for feedstocks
      with no pretreatment other than autoclaving and for solubilization mediated by C.
      thermocellum. As observed in prior studies, C. thermocellum fermentation results
      in a dramatic decrease in viscosity. The magnitude of this decrease, however, is
      much larger starting with unpretreated feedstock than previously reported for
      pretreated feedstocks. LAOS measurements provide a detailed picture of the
      rheological fingerprint of the material. Viscosity measurements confirm the
      hypothesis that the physical character of corn stover slurries changes
      dramatically during fermentation by C. thermocellum, and indicate that the energy
      expended on overcoming slurry viscosity will be far less for partially fermented
      corn stover than for unfermented corn stover.

PMID- 30202439
TI  - Mechanisms of microRNA-mediated gene regulation in unicellular model alga
      Chlamydomonas reinhardtii.
AB  - MicroRNAs are a class of endogenous non-coding RNAs that play a vital role in
      post-transcriptional gene regulation in eukaryotic cells. In plants and animals,
      miRNAs are implicated in diverse roles ranging from immunity against viral
      infections, developmental pathways, molecular pathology of cancer and regulation
      of protein expression. However, the role of miRNAs in the unicellular model green
      alga Chlamydomonas reinhardtii remains unclear. The mode of action of miRNA
      induced gene silencing in C. reinhardtii is very similar to that of higher
      eukaryotes, in terms of the activation of the RNA-induced silencing complex and
      mRNA targeting. Certain studies indicate that destabilization of mRNAs and mRNA
      turnover could be the major possible functions of miRNAs in eukaryotic algae.
      Here, we summarize recent findings that have advanced our understanding of miRNA
      regulatory mechanisms in C. reinhardtii.

PMID- 30202443
TI  - Familiar unbalanced complex rearrangements involving 13 p-arm: description of two
      cases.
AB  - Background: Copy number variations (CNVs) are largely known today, but their
      position is rarely established by fluorescence in situ hybridization (FISH) or
      karyotype analysis. Case presentation: We described two families with copy number
      gain in which FISH analysis with the specific subtelomeric probe of chromosome 4q
      and 7q evidenced a third signal at band 13p11.2. Genomic study by array
      comparative genomic hybridization defined the triple dose segment. In the first
      case, the duplicate tract is free of known genes, in the second one it contained
      three expressed genes. Conclusions: The CNV localization on the short arm of an
      acrocentric chromosome could explain the lack of phenotypic effect, being known
      the regulatory role of heterochromatin in the position-effect silencing.
      Furthermore, we would like to underline the importance of using complementary
      techniques such as FISH and array-CGH to obtain a better definition of genomic
      rearrangements.

PMID- 30202438
TI  - Development and characterization of stable anaerobic thermophilic methanogenic
      microbiomes fermenting switchgrass at decreasing residence times.
AB  - Background: Anaerobic fermentation of lignocellulose occurs in both natural and
      managed environments, and is an essential part of the carbon cycle as well as a
      promising route to sustainable production of fuels and chemicals. Lignocellulose
      solubilization by mixed microbiomes is important in these contexts. Results:
      Here, we report the development of stable switchgrass-fermenting enrichment
      cultures maintained at various residence times and moderately high (55  degrees
      C) temperatures. Anaerobic microbiomes derived from a digester inoculum were
      incubated at 55  degrees C and fed semi-continuously with medium containing 30
      g/L mid-season harvested switchgrass to achieve residence times (RT) of 20, 10,
      5, and 3.3 days. Stable, time-invariant cellulolytic methanogenic cultures with
      minimal accumulation of organic acids were achieved for all RTs. Fractional
      carbohydrate solubilization was 0.711, 0.654, 0.581 and 0.538 at RT = 20, 10, 5
      and 3.3 days, respectively, and glucan solubilization was proportional to xylan
      solubilization at all RTs. The rate of solubilization was described well by the
      equation r = k(C - C0fr), where C represents the concentration of unutilized
      carbohydrate, C0 is the concentration of carbohydrate (cellulose and
      hemicellulose) entering the bioreactor and fr is the extrapolated fraction of
      entering carbohydrate that is recalcitrant at infinite residence time. The 3.3
      day RT is among the shortest RT reported for stable thermophilic, methanogenic
      digestion of a lignocellulosic feedstock. 16S rDNA phylotyping and metagenomic
      analyses were conducted to characterize the effect of RT on community dynamics
      and to infer functional roles in the switchgrass to biogas conversion to the
      various microbial taxa. Firmicutes were the dominant phylum, increasing in
      relative abundance from 54 to 96% as RT decreased. A Clostridium clariflavum
      strain with genetic markers for xylose metabolism was the most abundant
      lignocellulose-solubilizing bacterium. A Thermotogae (Defluviitoga tunisiensis)
      was the most abundant bacterium in switchgrass digesters at RT = 20 days but
      decreased in abundance at lower RTs as did multiple Chloroflexi. Synergistetes
      and Euryarchaeota were present at roughly constant levels over the range of RTs
      examined. Conclusions: A system was developed in which stable methanogenic steady
      states were readily obtained with a particulate biomass feedstock, mid-season
      switchgrass, at laboratory (1 L) scale. Characterization of the extent and rate
      of carbohydrate solubilization in combination with 16S rDNA and metagenomic
      sequencing provides a multi-dimensional view of performance, species composition,
      glycoside hydrolases, and metabolic function with varying residence time. These
      results provide a point of reference and guidance for future studies and organism
      development efforts involving defined cultures.

PMID- 30202442
TI  - Chromosomes of Asian cyprinid fishes: cytogenetic analysis of two representatives
      of small paleotetraploid tribe Probarbini.
AB  - Background: Polyploidy, although still poorly explored, represents an important
      evolutionary event in several cyprinid clades. Herein, Catlocarpio siamensis and
      Probarbus jullieni - representatives of the paleotetraploid tribe Probarbini,
      were characterized both by conventional and molecular cytogenetic methods.
      Results: Alike most other paleotetraploid cyprinids (with 2n = 100), both species
      studied here shared 2n = 98 but differed in karyotypes: C. siamensis displayed
      18m + 34sm + 46st/a; NF = 150, while P. jullieni exhibited 26m + 14sm + 58st/a;
      NF = 138. Fluorescence in situ hybridization (FISH) with rDNA probes revealed two
      (5S) and eight (18S) signals in C. siamensis, respectively, and six signals for
      both probes in P. jullieni. FISH with microsatellite motifs evidenced substantial
      genomic divergence between both species. The almost doubled size of the
      chromosome pairs #1 in C. siamensis and #14 in P. jullieni compared to the rest
      of corresponding karyotypes indicated chromosomal fusions. Conclusion: Based on
      our findings, together with likely the same reduced 2n = 98 karyotypes in the
      remainder Probarbini species, we hypothesize that the karyotype 2n = 98 might
      represent a derived character, shared by all members of the Probarbini clade.
      Besides, we also witnessed considerable changes in the amount and distribution of
      certain repetitive DNA classes, suggesting complex post-polyploidization
      processes in this small paleotetraploid tribe.

PMID- 30202444
TI  - Grasping frequent subgraph mining for bioinformatics applications.
AB  - Searching for interesting common subgraphs in graph data is a well-studied
      problem in data mining. Subgraph mining techniques focus on the discovery of
      patterns in graphs that exhibit a specific network structure that is deemed
      interesting within these data sets. The definition of which subgraphs are
      interesting and which are not is highly dependent on the application. These
      techniques have seen numerous applications and are able to tackle a range of
      biological research questions, spanning from the detection of common
      substructures in sets of biomolecular compounds, to the discovery of network
      motifs in large-scale molecular interaction networks. Thus far, information about
      the bioinformatics application of subgraph mining remains scattered over
      heterogeneous literature. In this review, we provide an introduction to subgraph
      mining for life scientists. We give an overview of various subgraph mining
      algorithms from a bioinformatics perspective and present several of their
      potential biomedical applications.

PMID- 30202447
TI  - Management of adverse events during cyclin-dependent kinase 4/6 (CDK4/6)
      inhibitor-based treatment in breast cancer.
AB  - Cyclin-dependent kinase (CDK) 4/6 inhibitors have shown great results in numerous
      clinical trials and have improved the clinical outcome for patients with hormone
      receptor-positive, human epidermal growth factor receptor 2-negative advanced
      breast cancer significantly. To date, three CDK4/6 inhibitors are approved by the
      US Food and Drug Administration (FDA): palbociclib, ribociclib and abemaciclib;
      the first two compounds are aproved by the European Medicines Agency (EMA) as
      well. In combination with endocrine therapy, all of them led to significantly
      improved progression-free survival compared with endocrine therapy alone. The aim
      of this article is to give an overview of the efficacy data and to describe the
      CDK4/6 inhibitor-based treatment-associated adverse events, including
      hematological and nonhematological adverse events. In addition, it describes the
      corrrect approach to patient monitoring and adverse event mangement and
      summarizes the current recommendations for dose reductions and dose interruptions
      regarding the key adverse events, such as neutropenia, diarrhea, QTc prolongation
      and hepatobiliary toxicity. Accurate patient monitoring and management of the
      side effects is crucial, as several clinical trials in early breast cancer are in
      progress and may lead to an additional approval in the neo-/adjuvant setting.

PMID- 30202446
TI  - Peroneal muscle activity during different types of walking.
AB  - Background: As the most common form of movement, walking happens not only on flat
      but also on uneven surfaces, where constant loss and regaining of balance occur.
      The main balancing function of the ankle joint is performed by tibial muscles.
      When changing inclination in a frontal plane, an essential balancing function is
      performed by the peroneal muscles. One of the methods for improving the activity
      of peroneal muscles is walking with different foot placement. The objective of
      this study was to analyze the activity of the peroneal muscles when performing
      different types of walking. Methods: Sixteen healthy participants took part in
      this study, walking on a flat surface (NORM), on a medial incline ramp with the
      plantar surface of the foot fully placed on the surface (FULL), and on a medial
      incline ramp with elevated lateral part of the foot (LAT). We monitored the
      changes of EMG signals in peroneus longus (PL), peroneus brevis (PB), tibialis
      anterior (TA), soleus (SOL), gastrocnemius medialis (GM) and gastrocnemius
      lateralis (GL) muscles. We monitored kinematic parameters (gait speed, stride
      length, contact time, foot position). The parametric ANOVA test and a non
      parametric Friedman test were used at an alpha level of 0.05. Results: This study
      shows that the EMG activities of peroneal muscles increases when walking on the
      medial incline ramp. Statistically significant EMG differences were observed in
      the peroneal muscles, TA and GL muscles. We observe a very high percentage of
      normalized EMG value of the PL muscle in LAT walking. Walking on a medial incline
      ramp impacts the foot position, contact time, and stride length but not the gait
      speed. Conclusions: Walking on a medial incline ramp could be an effective
      exercise to improve the neuro-muscular function of the peroneal muscles and,
      therefore, might be a suitable exercise for people with weakened ankle evertors.

PMID- 30202445
TI  - Anticoagulant therapy in patients with liver cirrhosis and portal vein
      thrombosis: insights for the clinician.
AB  - Portal vein thrombosis (PVT) is a frequent complication in the natural history of
      patients with liver cirrhosis (LC). The prevalence of PVT in LC is highly
      variable, ranging from 0.6% to 25% according to different reports. The impact of
      PVT on the natural history of LC is unclear, but it seems to negatively affect
      the prognosis of patients undergoing liver transplantation (LT) by increasing
      post-LT mortality and delaying waiting time. The antithrombotic treatment of PVT
      is still challenging as PVT may often remain asymptomatic and incidentally
      diagnosed, and a spontaneous partial/total regression of PVT is observed in an
      important proportion of patients, even in the absence of anticoagulation. Recent
      evidence suggested that the anticoagulant treatment for PVT may favorably affect
      both ischemic and bleeding outcomes in LC patients. Anticoagulant therapies so
      far available include unfractioned heparin, low molecular weight heparins (LMWHs)
      and fondaparinux for acute treatment, and LMWHs and vitamin K antagonists (VKAs)
      for long-term treatment. No robust data currently support the use of direct oral
      anticoagulants (DOACs) in patients with LC and PVT, as the safety and efficacy of
      DOACs in this setting is still unclear. This review summarizes current evidence
      for the evaluation and management of patients with LC and PVT.

PMID- 30202448
TI  - Updates on managing advanced breast cancer with palbociclib combination therapy.
AB  - Background: The objective of this study was to review the pharmacology, efficacy,
      and safety of palbociclib, a first-in-class cyclin-dependent kinase 4/6
      inhibitor, for the management of advanced breast cancer (ABC). Methods:
      Pharmacokinetics and drug interactions associated with palbociclib are described.
      Recent clinical trial data are reviewed, including patient-reported outcomes and
      subgroup analyses. Results: Palbociclib is indicated in combination with an
      aromatase inhibitor as initial endocrine therapy (ET) or with fulvestrant for
      patients with disease progression following ET for hormone receptor positive,
      human epidermal growth factor receptor 2 negative ABC or metastatic breast
      cancer. Palbociclib inhibits cyclin-dependent kinases 4/6, resulting in a
      blockade of phosphorylation of the retinoblastoma protein, which hinders the
      activation of transcription factors involved in S-phase entry, thereby arresting
      cell cycle progression at G1 phase. The efficacy and safety of palbociclib in
      combination with ET was established in three randomized trials (PALOMA-1, -2, and
      -3); all studies met their primary endpoint of significantly prolonging
      investigator-assessed progression-free survival versus ET alone. Findings were
      similar in subgroup analyses of the three PALOMA studies. Palbociclib plus ET
      also maintained health-related quality of life (QoL) compared with ET alone in
      PALOMA-2 and -3. A long-term safety profile for palbociclib, up to 3 years, has
      been established. Neutropenia, the most common any-grade and grade 3 or higher
      adverse event associated with palbociclib, is consistent with the drug's
      mechanism of action and can be effectively managed with dose interruption, dose
      reduction, or delay in starting treatment cycles. Conclusions: Palbociclib in
      combination with ET improved progression-free survival and QoL in patients with
      ABC, including in several patient subgroups.

PMID- 30202449
TI  - Synthesis and characterization of pi-extended "earring" subporphyrins.
AB  - A pi-extended "earring" subporphyrin 3 was synthesized from beta,beta'
      diiodosubporphyrin and diboryltripyrrane via a Suzuki-Miyaura coupling and
      following oxidation. Its Pd complex 3Pd was also synthesized and both of the
      compounds were fully characterized by 1H NMR, MS and X-ray single crystal
      diffraction. The 1H NMR spectra and single crystal structures revealed that
      aromatic ring current did not extend to the "ear" in both of the two compounds.
      Their UV-vis/NIR spectra were recorded and the absorption of both compounds is
      extended to the NIR region and that the absorption of 3Pd is further red-shifted
      and more intense.

PMID- 30202451
TI  - Cationic cobalt-catalyzed [1,3]-rearrangement of N-alkoxycarbonyloxyanilines.
AB  - A cationic cobalt catalyst efficiently promoted the reaction of N
      alkoxycarbonyloxyanilines at 30  degrees C, affording the corresponding ortho
      aminophenols in good to high yields. As reported previously, our mechanistic
      studies including oxygen-18 labelling experiments indicate that the rearrangement
      of the alkoxycarbonyloxy group proceeds in [1,3]-manner. In this article, we
      discuss the overall picture of the cobalt-catalysed [1,3]-rearrangement reaction
      including details of the reaction conditions and substrate scope.

PMID- 30202450
TI  - Rational design of boron-dipyrromethene (BODIPY) reporter dyes for
      cucurbit[7]uril.
AB  - We introduce herein boron-dipyrromethene (BODIPY) dyes as a new class of
      fluorophores for the design of reporter dyes for supramolecular host-guest
      complex formation with cucurbit[7]uril (CB7). The BODIPYs contain a protonatable
      aniline nitrogen in the meso-position of the BODIPY chromophore, which was
      functionalized with known binding motifs for CB7. The unprotonated dyes show low
      fluorescence due to photoinduced electron transfer (PET), whereas the protonated
      dyes are highly fluorescent. Encapsulation of the binding motif inside CB7
      positions the aniline nitrogen at the carbonyl rim of CB7, which affects the pKa
      value, and leads to a host-induced protonation and thus to a fluorescence
      increase. The possibility to tune binding affinities and pKa values is
      demonstrated and it is shown that, in combination with the beneficial
      photophysical properties of BODIPYs, several new applications of host-dye
      reporter pairs can be implemented. This includes indicator displacement assays
      with favourable absorption and emission wavelengths in the visible spectral
      region, fluorescence correlation spectroscopy, and noncovalent surface
      functionalization with fluorophores.

PMID- 30202452
TI  - Synthesis of new p-tert-butylcalix[4]arene-based polyammonium triazolyl
      amphiphiles and their binding with nucleoside phosphates.
AB  - The synthesis of new calix[4]arenes adopting a cone stereoisomeric form bearing
      two or four azide fragments on the upper rim and water-soluble triazolyl
      amphiphilic receptors with two or four polyammonium headgroups via copper
      catalyzed azide-alkyne cycloaddition reaction has been performed for the first
      time. It was found that the synthesized macrocycles form stable aggregates with
      hydrodynamic diameters between 150-200 nm and electrokinetic potentials about +40
      to +60 mV in water solutions. Critical aggregation concentration (CAC) values
      were measured using a micelle method with pyrene and eosin Y as dye probes. The
      CAC values of tetraalkyl-substituted macrocycles 12a,b (5 uM for both) are
      significantly lower than those for dialkyl-substituted macrocycles 10a,b (790 and
      160 uM, respectively). Premicellar aggregates of macrocycles 10a,b and 12a,b with
      the dye eosin Y were used for nucleotides sensing through a dye replacement
      procedure. It is unusual that disubstituted macrocycles 10a,b bind more
      effectively a less charged adenosine 5'-diphosphate (ADP) than adenosine 5'
      triphosphate (ATP). A simple colorimetric method based on polydiacetylene
      vesicles decorated with 10b was elaborated for the naked-eye detection of ADP
      with a detection limit of 0.5 mM.

PMID- 30202453
TI  - A self-assembled photoresponsive gel consisting of chiral nanofibers.
AB  - A novel compound based on a glutamic acid skeleton, containing azobenzene as a
      photoresponsive group and ureidopyrimidinone (UPy) as a connection site, was
      designed and synthesized. The monomer is capable of forming an organogel in
      nonpolar organic solvents and different types of nanostructures in other
      solvents. The state of the gel and the chirality of the nanostructures could both
      be adjusted by subsequent light irradiation at different wavelengths. The helical
      nanofiber-like morphology was verified in the internal structure of the gel. The
      performance of this gel was investigated by a series of methods, such as UV-vis
      absorption spectroscopy, circular dichroism, scanning electron microscopy and
      rheological techniques. This work provides a new method for facile synthesis of
      chiro-optical gels.

PMID- 30202454
TI  - Chiral bisoxazoline ligands designed to stabilize bimetallic complexes.
AB  - Chiral bisoxazoline ligands containing naphthyridine, pyridazine, pyrazole, and
      phenol bridging units were prepared and shown to form bimetallic complexes with
      various metal salts. X-ray crystal structures of bis-nickel naphthyridine
      bridged, bis-zinc pyridazine-bridged, and bis-nickel as well as bis-palladium
      pyrazole-bridged complexes were obtained.

PMID- 30202455
TI  - Cobalt-catalyzed nucleophilic addition of the allylic C(sp3)-H bond of simple
      alkenes to ketones.
AB  - We herein describe a cobalt/Xantphos-catalyzed regioselective addition of simple
      alkenes to acetophenone derivatives, affording branched homoallylic alcohols in
      high yields with perfect branch selectivities. The intermediate of the reaction
      would be a nucleophilic allylcobalt(I) species generated via cleavage of the low
      reactive allylic C(sp3)-H bond of simple terminal alkenes.

PMID- 30202456
TI  - Functionalization of graphene: does the organic chemistry matter?
AB  - Reactions applying amidation- or esterification-type processes and diazonium
      salts chemistry constitute the most commonly applied synthetic approaches for the
      modification of graphene-family materials. This work presents a critical
      assessment of the amidation and esterification methodologies reported in the
      recent literature, as well as a discussion of the reactions that apply diazonium
      salts. Common misunderstandings from the reported covalent functionalization
      methods are discussed, and a direct link between the reaction mechanisms and the
      basic principles of organic chemistry is taken into special consideration.

PMID- 30202457
TI  - Coordination-driven self-assembly vs dynamic covalent chemistry: versatile
      methods for the synthesis of molecular metallarectangles.
AB  - Supramolecular coordination assemblies have a range of potential applications in
      chemical and biological sciences. Herein, simple modular methods for the
      synthesis of metallarectangles are described. The desired tetranuclear
      metallarectangles were synthesized by using coordination-driven self-assembly of
      half-sandwich rhodium-based organometallic clip units and organic ligands. The
      reaction of such an organometallic clip with 4-formylpyridine provided a
      dinuclear molecular tweezer with pendant aldehyde groups, and subsequent [4 + 4]
      condensation reactions with diamines provides another route to the target
      metallarectangles in good yields. The same assemblies can also be easily isolated
      in one-pot procedures by mixing the organometallic clip, diamines and 4
      formylpyridine.

PMID- 30202458
TI  - Applications of organocatalysed visible-light photoredox reactions for medicinal
      chemistry.
AB  - The focus of this review is to provide an overview of the field of
      organocatalysed photoredox chemistry relevant to synthetic medicinal chemistry.
      Photoredox transformations have been shown to enable key transformations that are
      important to the pharmaceutical industry. This type of chemistry has also
      demonstrated a high degree of sustainability, especially when organic dyes can be
      employed in place of often toxic and environmentally damaging transition metals.
      The sections are arranged according to the general class of the presented
      reactions and the value of these methods to medicinal chemistry is considered. An
      overview of the general characteristics of the photocatalysts as well as some
      electrochemical data is presented. In addition, the general reaction mechanisms
      for organocatalysed photoredox transformations are discussed and some individual
      mechanistic considerations are highlighted in the text when appropriate.

PMID- 30202459
TI  - Synthesis and supramolecular self-assembly of glutamic acid-based squaramides.
AB  - We describe the preparation and characterization of two new unsymmetrical
      squaramide-based organogelators. The synthesis of the compounds was carried out
      by subsequent amine condensations starting from dimethyl squarate. The design of
      the gelators involved a squaramide core connected on one side to a long aliphatic
      chain and on the other side to a glutamic acid residue. The gelator bearing the
      free carboxylic groups showed a lower gelation capacity than its precursor
      diester derivative. Some selected gels were further studied by infrared
      spectroscopy, rheology and electron microscopy. Critical gelation concentrations
      and gel-to-sol transition temperatures were also determined for each case. In
      addition, the superior squaramide diester gelator was compared with an analogue
      triazole-based gelator in terms of critical gelation concentration, gelation
      kinetics and thermal phase transition.

PMID- 30202460
TI  - A switchable [2]rotaxane with two active alkenyl groups.
AB  - A novel functional [2]rotaxane containing two alkenyl bonds was designed,
      synthesized and characterized by 1H, 13C NMR spectroscopy and HRESI mass
      spectrometry. The introduction of alkenyl bonds endowed the [2]rotaxane a
      fascinating ability to react with versatile functional groups such as alkenyl and
      thiol functional groups. The reversible shuttling movement of the macrocycle
      between two different recognition sites on the molecular thread can be driven by
      external acid and base. This kind of rotaxane bearing functional groups provides
      a powerful platform for preparing stimuli-responsive polymers.

PMID- 30202461
TI  - D-Fructose-based spiro-fused PHOX ligands: synthesis and application in
      enantioselective allylic alkylation.
AB  - Phosphinooxazoline (PHOX) ligands are an important class of ligands in asymmetric
      catalysis. We synthesized ten novel D-fructose-derived spiro-fused PHOX ligands
      with different steric and electronic demand. The application of two of them was
      tested in asymmetric allylic alkylation. The ligands are prepared in two steps
      from readily available 1,2-O-isopropylidene protected beta-D-fructopyranoses by
      the BF3.OEt2-promoted Ritter reaction with 2-bromobenzonitrile to construct the
      oxazoline moiety followed by Ullmann coupling of the resulting aryl bromides with
      diphenylphosphine. Both steps proceeded mostly in good to high yields (57-86% for
      the Ritter reaction and 35-89% for the Ullmann coupling). The Ritter reaction
      gave two anomers, which could be separated by column chromatography. The prepared
      ligands showed promising results (er of up to 84:16) in Tsuji-Trost reactions
      with diphenylallyl acetate as model substrate.

PMID- 30202462
TI  - Cobalt-catalyzed peri-selective alkoxylation of 1-naphthylamine derivatives.
AB  - A cobalt-catalyzed C(sp2)-H alkoxylation of 1-naphthylamine derivatives has been
      disclosed, which represents an efficient approach to synthesize aryl ethers with
      broad functional group tolerance. It is noteworthy that secondary alcohols, such
      as hexafluoroisopropanol, isopropanol, isobutanol, and isopentanol, were well
      tolerated under the current catalytic system. Moreover, a series of biologically
      relevant fluorine-aryl ethers were easily obtained under mild reaction conditions
      after the removal of the directing group.

PMID- 30202463
TI  - Revisiting ring-degenerate rearrangements of 1-substituted-4-imino-1,2,3
      triazoles.
AB  - The 1-substituted-4-imino-1,2,3-triazole motif is an established component of
      coordination compounds and bioactive molecules, but depending on the substituent
      identity, it can be inherently unstable due to Dimroth rearrangements. This study
      examined parameters governing the ring-degenerate rearrangement reactions of 1
      substituted-4-imino-1,2,3-triazoles, expanding on trends first observed by L'abbe
      et al. The efficiency of condensation between 4-formyltriazole and amine
      reactants as well as the propensity of imine products towards rearrangement was
      each strongly influenced by the substituent identity. It was observed that
      unsymmetrical condensation reactions conducted at 70  degrees C produced up to
      four imine products via a dynamic equilibrium of condensation, rearrangement and
      hydrolysis steps. Kinetic studies utilizing 1-(4-nitrophenyl)-1H-1,2,3-triazole-4
      carbaldehyde with varying amines showed rearrangement rates sensitive to both
      steric and electronic factors. Such measurements were facilitated by a high
      throughput colorimetric assay to directly monitor the generation of a 4
      nitroaniline byproduct.

PMID- 30202464
TI  - Studies towards the synthesis of hyperireflexolide A.
AB  - The first approach to hyperireflexolide A, based on the synthesis of gamma
      lactone-fused cyclopentane 5, a functionalized key intermediate, is presented.
      Compound 5 is involved in hydrolysis, alpha-allylation at C-8 and alpha
      methylation at C-10 stereoselectively from the convex face. Then it is subjected
      to cross metathesis to give alpha,beta-unsaturated ketone 11 as precursor in the
      total synthesis of hyperireflexolide A.

PMID- 30202465
TI  - Calix[6]arene-based atropoisomeric pseudo[2]rotaxanes.
AB  - Some examples of atropoisomeric pseudorotaxanes in which the isomerism arises by
      the different conformations adopted by the wheel are reported here. Upon
      threading hexahexyloxycalix[6]arene 1 with ammonium axles 2+ or 3+ , bearing
      biphenyl or trifluoromethylbenzyl moieties, respectively, two atropoisomeric
      pseudorotaxanes were formed in which the calix[6]-wheel 1 adopts the 1,2,3
      alternate and cone conformations. The interconversion between them cannot be
      obtained by simple rotation around the ArCH2Ar bonds of the calixarene wheel,
      which is blocked by the presence of the axle inside its cavity. Therefore, it can
      only be obtained through a mechanism of de-threading/re-threading of the axle. In
      all the examined cases, the 1,2,3-alternate and cone atropoisomers are,
      respectively, the kinetic and the thermodynamic ones.

PMID- 30202466
TI  - Evaluation of dispersion type metal...pi arene interaction in arylbismuth
      compounds - an experimental and theoretical study.
AB  - The dispersion type Bi...pi arene interaction is one of the important structural
      features in the assembly process of arylbismuth compounds. Several triarylbismuth
      compounds and polymorphs are discussed and compared based on the analysis of
      single crystal X-ray diffraction data and computational studies. First, the
      crystal structures of polymorphs of Ph3Bi (1) are described emphasizing on the
      description of London dispersion type bismuth...pi arene interactions and other
      van der Waals interactions in the solid state and the effect of it on
      polymorphism. For comparison we have chosen the substituted arylbismuth compounds
      (C6H4-CH?CH2-4)3Bi (2), (C6H4-OMe-4)3Bi (3), (C6H3-t-Bu2-3,5)3Bi (4) and (C6H3-t
      Bu2-3,5)2BiCl (5). The structural analyses revealed that only two of them show
      London dispersion type bismuth...pi arene interactions. One of them is the styryl
      derivative 2, for which two polymorphs were isolated. Polymorph 2a crystallizes
      in the orthorhombic space group P212121, while polymorph 2b exhibits the
      monoclinic space group P21/c. The general structure of 2a is similar to the
      monoclinic C2/c modification of Ph3Bi (1a), which leads to the formation of zig
      zag Bi-arenecentroid ribbons formed as a result of bismuth...pi arene
      interactions and pi...pi intermolecular contacts. In the crystal structures of
      the polymorph 2b as well as for 4 bismuth...pi arene interactions are not
      observed, but both compounds revealed C-HPh...pi intermolecular contacts, as
      likewise observed in all of the three described polymorphs of Ph3Bi. For compound
      3 intermolecular contacts as a result of coordination of the methoxy group to
      neighboring bismuth atoms are observed overruling Bi...pi arene contacts.
      Compound 5 shows a combination of donor acceptor Bi...Cl and Bi...pi arene
      interactions, resulting in an intermolecular pincer-type coordination at the
      bismuth atom. A detailed analysis of three polymorphs of Ph3Bi (1), which were
      chosen as model systems, at the DFT-D level of theory supported by DLPNO-CCSD(T)
      calculations reveals how van der Waals interactions between different structural
      features balance in order to stabilize molecular arrangements present in the
      crystal structure. Furthermore, the computational results allow to group this
      class of compounds into the range of heavy main group element compounds which
      have been characterized as dispersion energy donors in previous work.

PMID- 30202468
TI  - Synthesis of 1,4-imino-L-lyxitols modified at C-5 and their evaluation as
      inhibitors of GH38 alpha-mannosidases.
AB  - A synthetic approach to 1,4-imino-L-lyxitols with various modifications at the C
      5 position is reported. These imino-L-lyxitol cores were used for the preparation
      of a series of N-(4-halobenzyl)polyhydroxypyrrolidines. An impact of the C-5
      modification on the inhibition and selectivity against GH38 alpha-mannosidases
      from Drosophila melanogaster, the Golgi (GMIIb) and lysosomal (LManII)
      mannosidases and commercial jack bean alpha-mannosidase from Canavalia ensiformis
      was evaluated. The modification at C-5 affected their inhibitory activity against
      the target GMIIb enzyme. In contrast, no inhibition effect of the pyrrolidines
      against LManII was observed. The modification of the imino-L-lyxitol core is
      therefore a suitable motif for the design of inhibitors with desired selectivity
      against the target GMIIb enzyme.

PMID- 30202467
TI  - Hypervalent iodine compounds for anti-Markovnikov-type iodo-oxyimidation of
      vinylarenes.
AB  - The iodo-oxyimidation of styrenes with the N-hydroxyimide/I2/hypervalent iodine
      oxidant system was proposed. Among the examined hypervalent iodine oxidants
      (PIDA, PIFA, IBX, DMP) PhI(OAc)2 proved to be the most effective; yields of iodo
      oxyimides are 34-91%. A plausible reaction pathway includes the addition of an
      imide-N-oxyl radical to the double C=C bond and trapping of the resultant
      benzylic radical by iodine. It was shown that the iodine atom in the prepared
      iodo-oxyimides can be substituted by various nucleophiles.

PMID- 30202470
TI  - Synergistic electrodeposition of bilayer films and analysis by Raman
      spectroscopy.
AB  - A novel methodology towards fabrication of multilayer organic devices, employing
      electrochemical polymer growth to form PEDOT and PEDTT layers, is successfully
      demonstrated. Moreover, careful control of the electrochemical conditions allows
      the degree of doping to be effectively altered for one of the polymer layers.
      Raman spectroscopy confirmed the formation and doped states of the PEDOT/PEDTT
      bilayer. The electrochemical deposition of a bilayer containing a de-doped PEDTT
      layer on top of doped PEDOT is analogous to a solution-processed organic
      semiconductor layer deposited on top of a PEDOT:PSS layer without the acidic PSS
      polymer. However, the poor solubility of electrochemically deposited PEDTT (or
      other electropolymerised potential candidates) raises the possibility of
      depositing a subsequent layer via solution-processing.

PMID- 30202469
TI  - Tetrathiafulvalene - a redox-switchable building block to control motion in
      mechanically interlocked molecules.
AB  - With the rise of artificial molecular machines, control of motion on the
      nanoscale has become a major contemporary research challenge. Tetrathiafulvalenes
      (TTFs) are one of the most versatile and widely used molecular redox switches to
      generate and control molecular motion. TTF can easily be implemented as
      functional unit into molecular and supramolecular structures and can be
      reversibly oxidized to a stable radical cation or dication. For over 20 years,
      TTFs have been key building blocks for the construction of redox-switchable
      mechanically interlocked molecules (MIMs) and their electrochemical operation has
      been thoroughly investigated. In this review, we provide an introduction into the
      field of TTF-based MIMs and their applications. A brief historical overview and a
      selection of important examples from the past until now are given. Furthermore,
      we will highlight our latest research on TTF-based rotaxanes.

PMID- 30202471
TI  - Synthesis and post-functionalization of alternate-linked-meta-para-[2 n .1 n
      ]thiacyclophanes.
AB  - In recent decades, considerable research attention has been devoted to new
      synthetic procedures for thiacyclophanes. Thiacyclophanes are widely used as host
      molecules for the molecular recognition of organic compounds as well as metals.
      Herein, we report the selective and high-yielding synthesis of novel alternate
      linked-meta-para-thiacyclophanes. These novel thiacyclophanes are selectively
      synthesized in high-yielding procedures. Furthermore, post-functionalization of
      the phenolic moieties was successfully performed. The 3D structure of the
      alternate-linked-meta-para-[22.12]thiacyclophane was further elucidated via X-ray
      crystallographic analysis.

PMID- 30202472
TI  - Bi-mediated allylation of aldehydes in [bmim][Br]: a mechanistic investigation.
AB  - The inexpensive room temperature ionic liquid (RTIL), [bmim][Br] has been found
      to be a superior medium for the Bi-mediated Barbier-type allylation of aldehydes
      compared to other conventional solvents. It plays the dual role of a solvent and
      a metal activator enabling higher yields of the products in a shorter reaction
      time using stoichiometric/near-stoichiometric amounts of reagents. Plausibly,
      [bmim][Br] activates Bi metal by a charge transfer mechanism. The 1H VT-NMR
      studies suggested that both the allylating species, allylbismuth dibromide and
      diallylbismuth bromide, are generated in situ.

PMID- 30202473
TI  - Selective formation of a zwitterion adduct and bicarbonate salt in the efficient
      CO2 fixation by N-benzyl cyclic guanidine under dry and wet conditions.
AB  - The efficient CO2 fixation by N-benzyl cyclic guanidine 1 was achieved by
      bubbling dry CO2 through CH3CN at 25  degrees C for 2 h. In addition, the
      zwitterion adduct 2 and bicarbonate salt 3 were selectively prepared from 1 under
      dry (in anhydrous CH3CN) and wet (in CH3CN containing an equimolar amount of
      water for 1) conditions, respectively. Both compounds 2 and 3 were isolated as
      white solids and their structures were characterized in detail by elemental
      analysis, FTIR-ATR, solid-state NMR, TGA, and DFT calculation. These analytical
      results obviously revealed the formation of a zwitterion adduct and bicarbonate
      salt from N-benzyl cyclic guanidine and CO2. Especially, the zwitterion adduct of
      the monocyclic guanidine derivative and CO2 was isolated and characterized for
      the first time.

PMID- 30202474
TI  - Dynamic light scattering studies of the effects of salts on the diffusivity of
      cationic and anionic cavitands.
AB  - Although alkali halide salts play key roles in all living systems, the physical
      models used to describe the properties of aqueous solutions of salts do not take
      into account specific ion-ion interactions. To identify specific ion-ion
      interactions possibly contributing to the aggregation of proteins, we have used
      dynamic light scattering (DLS) to probe the aggregation of charged cavitands. DLS
      measurements of negatively charged 1 in the presence of a range of alkali metal
      halides reveal no significant aggregation of host 1 as a function of the nature
      of the cation of the added salt. Only at high concentrations could trace amounts
      of aggregation be detected by 1H NMR spectroscopy. Contrarily, 1 was readily
      aggregated and precipitated by ZnCl2. In contrast, although fluoride and chloride
      did not induce aggregation of positively charged host 2, this cavitand exhibited
      marked aggregation as a function of bromide and iodide concentration.
      Specifically, bromide induced small but significant amounts of dimerization,
      whilst iodide induced extreme aggregation. Moreover, in these cases aggregation
      of host 2 also exhibited a cationic dependence, with an observed trend Na+ > Li+
      > K+ ~ Cs+. In combination, these results reveal new details of specific ion
      pairings in aqueous solution and how this can influence the properties of
      dissolved organics.

PMID- 30202475
TI  - A general and atom-efficient continuous-flow approach to prepare amines, amides
      and imines via reactive N-chloramines.
AB  - Chloramines are an important class of reagents, providing a convenient source of
      chlorine or electrophilic nitrogen. However, the instability of these compounds
      is a problem which makes their isolation and handling difficult. To overcome
      these hazards, a continuous-flow approach is reported which generates and
      immediately reacts N-chloramines directly, avoiding purification and isolation
      steps. 2-Chloramines were produced from the reaction of styrenes with N-alkyl-N
      sulfonyl-N-chloramines, whilst N-alkyl or N,N'-dialkyl-N-chloramines reacted with
      anisaldehyde in the presence of t-BuO2H oxidant to afford amides. Primary and
      secondary imines were produced under continuous conditions from the reaction of N
      chloramines with base, with one example subsequently reduced under asymmetric
      conditions to produce a chiral amine in 94% ee.

PMID- 30202476
TI  - Investigation of the electrophilic reactivity of the biologically active marine
      sesquiterpenoid onchidal and model compounds.
AB  - The structure of the sesquiterpene onchidal (6), a component of the defensive
      secretion of the shell-less mollusc Onchidella binneyi, contains a masked
      alpha,beta-unsaturated 1,4-dialdehyde moiety, the presence of which has been
      proposed to be the cause of the feeding deterrent activity exhibited by the
      mollusc. We have found onchidal acts as an electrophile, reacting rapidly with
      the model nucleophile n-pentylamine forming diastereomeric aminated pyrrole
      adducts. Somewhat surprisingly, no reaction was observed between onchidal and n
      pentanethiol. Structurally simplified n-pentyl 11-13 and cyclohexylmethyl 15-17
      analogues of onchidal were prepared and demonstrated similar amine-selective
      reactivity. Onchidal and analogues reacted with the model protein lysozyme,
      forming covalent adducts and leading to protein cross-linking. These results
      provide preliminary evidence supporting the molecular mechanism of biological
      activity exhibited by onchidal.

PMID- 30202477
TI  - Synthesis of a water-soluble 2,2'-biphen[4]arene and its efficient complexation
      and sensitive fluorescence enhancement towards palmatine and berberine.
AB  - A water-soluble 2,2'-biphen[4]arene (2,2'-CBP4) containing eight carboxylato
      moieties was synthesized and characterized. Its complexation behavior towards two
      alkaloids, palmatine (P) and berberine (B), was investigated by means of
      fluorescence and 1H NMR spectroscopy in aqueous phosphate buffer solution (pH
      7.4). In the presence of 2,2'-CBP4, 1H NMR signals of P and B displayed very
      large upfield shifts, indicating the formation of inclusion complexes with strong
      binding affinities. Fluorescence titration experiments showed that P and B
      exhibited dramatic fluorescence enhancement of more than 600 times upon
      complexation with 2,2'-CBP4. Particularly, the fluorescence intensity is strong
      enough to be readily distinguished by the naked eye. Although the two guests have
      similar structures, the association constant of B with 2,2'-CBP4 (Ka = (2.29 +/-
      0.27) * 106 M-1) is 3.9 times larger than that of P (Ka = (5.87 +/- 0.24) * 105 M
      1).

PMID- 30202479
TI  - Novel photochemical reactions of carbocyclic diazodiketones without elimination
      of nitrogen - a suitable way to N-hydrazonation of C-H-bonds.
AB  - The sensitized photoexcitation of 2-diazocyclopentane-1,3-diones in the presence
      of THF leads to the insertion of the terminal N-atom of the diazo group into the
      alpha-S-N bond of THF, producing the associated N-alkylhydrazones in yields of up
      to 63-71%. Further irradiation of hydrazones derived from furan-fused tricyclic
      diazocyclopentanediones culminates in the cycloelimination of furans to yield 2-N
      (alkyl)hydrazone of cyclopentene-1,2,3-trione. By contrast, the direct photolysis
      of carbocyclic diazodiketones gives only Wolff rearrangement products with up to
      90-97% yield.

PMID- 30202478
TI  - Coordination-driven self-assembly of discrete Ru6-Pt6 prismatic cages.
AB  - The coordination-driven self-assembly of two new Ru6-Pt6 hexanuclear trigonal
      prismatic cages comprising arene-ruthenium(II) clips (1a(NO3)2 and 1b(NO3)2 ) and
      a tritopic platinum(II) metalloligand 2 has been performed in methanol at room
      temperature. The [3 + 2] hexanuclear cages 3a and 3b were isolated in good yields
      and characterized by well-known spectroscopic techniques including multinuclear
      NMR, mass spectrometry, UV-vis and infrared studies. Geometry optimization
      revealed the shapes and sizes of these hexanuclear prismatic cages. The
      combination of ruthenium and platinum metal center in a one-pot self-assembly
      reaction showcases the construction of aesthetically elegant heterometallic
      structures in supramolecular chemistry leading to the formation of a single major
      product.

PMID- 30202480
TI  - Cobalt bis(acetylacetonate)-tert-butyl hydroperoxide-triethylsilane: a general
      reagent combination for the Markovnikov-selective hydrofunctionalization of
      alkenes by hydrogen atom transfer.
AB  - We show that cobalt bis(acetylacetonate) [Co(acac)2], tert-butyl hydroperoxide
      (TBHP), and triethylsilane (Et3SiH) constitute an inexpensive, general, and
      practical reagent combination to initiate a broad range of Markovnikov-selective
      alkene hydrofunctionalization reactions. These transformations are believed to
      proceed by cobalt-mediated hydrogen atom transfer (HAT) to the alkene substrate,
      followed by interception of the resulting alkyl radical intermediate with a
      SOMOphile. In addition, we report the first reductive couplings of unactivated
      alkenes and aryldiazonium salts by an HAT pathway. The simplicity and generality
      of the Co(acac)2-TBHP-Et3SiH reagent combination suggests it as a useful starting
      point to develop HAT reactions in complex settings.

PMID- 30202481
TI  - Hydroarylations by cobalt-catalyzed C-H activation.
AB  - As an earth-abundant first-row transition metal, cobalt catalysts offer a broad
      range of economical methods for organic transformations via C-H activation. One
      of the transformations is the addition of C-H to C-X multiple bonds to afford
      alkylation, alkenation, amidation, and cyclization products using low- or high
      valent cobalt catalysts. This hydroarylation is an efficient approach to build
      new C-C bonds in a 100% atom-economical manner. In this review, the recent
      developments of Co-catalyzed hydroarylation reactions and their mechanistic
      studies are summarized.

PMID- 30202482
TI  - Determining the predominant tautomeric structure of iodine-based group-transfer
      reagents by 17O NMR spectroscopy.
AB  - Cyclic benziodoxole systems have become a premier scaffold for the design of
      electrophilic transfer reagents. A particularly intriguing aspect is the
      fundamental II-IIII tautomerism about the hypervalent bond, which has led in
      certain cases to a surprising re-evaluation of the classic hypervalent structure.
      Thus, through a combination of 17O NMR spectroscopy at natural abundance with DFT
      calculations, we establish a convenient method to provide solution-phase
      structural insights for this class of ubiquitous reagents. In particular, we
      confirm that Shen's revised, electrophilic SCF3-transfer reagent also adopts an
      "acyclic" thioperoxide tautomeric form in solution. After calibration, the
      approach described herein likely provides a more general and direct method to
      distinguish between cyclic and acyclic structural features based on a single
      experimental 17O NMR spectrum and a computationally-derived isotropic shift
      value. Furthermore, we apply this structural elucidation technique to predict the
      constitution of an electrophilic iodine-based cyano-transfer reagent as an NC-I-O
      motif and study the acid-mediated activation of Togni's trifluoromethylation
      reagent.

PMID- 30202485
TI  - Predatory Publisher Attempts to Compromise WestJEM's Integrity.

PMID- 30202484
TI  - Treatment of Zygomatic Complex Fractures with Surgical or Nonsurgical
      Intervention: A Retrospective Study.
AB  - Objective: Evaluate the 1-year treatment outcome of zygomatic complex fractures
      with surgical or nonsurgical intervention. Materials and Methods: One hundred and
      forty-two consecutive patients with a zygomatic complex fracture were enrolled.
      Sixty-eight patients underwent surgical intervention and 74 patients nonsurgical
      intervention. The 1-year examination evaluated cosmetic and functional outcome
      including malar symmetry, ocular motility, occlusion, mouth opening, neurosensory
      disturbances, and complications. Results: Forty-six patients allocated to
      surgical intervention responded to the 1-year follow-up examination. Satisfying
      facial contour and malar alignment was observed in 45 patients. All patients
      presented with identical position of the eye globe without enophthalmos and
      normal ocular movement. A habitual occlusion was seen in all patients with a mean
      interincisal mouth opening without pain of 49 mm. One patient presented with
      minor ectropion. Wound infection occurred in five patients. Persistent
      infraorbital neurosensory disturbance was described by 19 patients. The 1-year
      radiographic examination showed adequate fracture alignment in all patients with
      satisfying facial contour. However, dissimilar position of the orbital floor was
      seen in three patients having orbital reconstruction. None of the patients were
      re-operated or needed secondary correction of the zygomatic complex or orbital
      floor. Conclusion: Surgical intervention is an effective treatment modality of
      depressed zygomatic complex fractures, whereas a nonsurgical approach is often
      used for nondisplaced fractures. Most zygomatic complex fractures can be treated
      solely by an intraoral approach and rigid fixation at the zygomaticomaxillary
      buttress. Further exposure of the zygomaticofrontal junction or inferior orbital
      rim is necessary for severely displaced fractures, which require additional
      fixation.

PMID- 30202483
TI  - The enzymes of microbial nicotine metabolism.
AB  - Because of nicotine's toxicity and the high levels found in tobacco and in the
      waste from tobacco processing, there is a great deal of interest in identifying
      bacteria capable of degrading it. A number of microbial pathways have been
      identified for nicotine degradation. The first and best-understood is the
      pyridine pathway, best characterized for Arthrobacter nicotinovorans, in which
      the first reaction is hydroxylation of the pyridine ring. The pyrrolidine
      pathway, which begins with oxidation of a carbon-nitrogen bond in the pyrrolidine
      ring, was subsequently characterized in a number of pseudomonads. Most recently,
      a hybrid pathway has been described, which incorporates the early steps in the
      pyridine pathway and ends with steps in the pyrrolidine pathway. This review
      summarizes the present status of our understanding of these pathways, focusing on
      what is known about the individual enzymes involved.

PMID- 30202486
TI  - Blunt Trauma Abdominal and Pelvic Computed Tomography Has Low Yield for Injuries
      in More Than One Anatomic Region.
AB  - Introduction: Most trauma centers order abdominal and pelvic computed tomography
      (CT) as an automatically paired CT for adult blunt trauma evaluation. However,
      excessive CT utilization adds risks of excessive exposure to ionizing radiation,
      the need to work up incidental findings (leading to unnecessary and invasive
      tests), and greater costs. Examining a cohort of adult blunt trauma patients that
      received paired abdominal and pelvic (A/P) CT, we sought to determine the
      diagnostic yield of clinically significant injuries (CSI) in the following: 1)
      the abdomen alone; 2) the pelvis alone; 3) the lumbosacral spine alone; and 4)
      more than one of these anatomic regions concomitantly. Methods: In this
      retrospective study, we reviewed the imaging and hospital course of a consecutive
      sample of blunt trauma activation patients older than 14 years of age who
      received paired A/P CT during their blunt trauma assessments at an urban Level I
      trauma center from April through October 2014. Categorization of CSI was
      determined according to an a priori, expert panel-derived classification scheme.
      Results: The median age of the 689 patients who had A/P CT was 48 years old;
      68.1% were male; 64.0% were admitted, and hospital mortality was 3.6%. CSI yields
      were as follows: abdomen 2.2% (95% confidence interval [CI] [1.3-3.6%]); pelvis
      2.9% (95% CI [1.9-4.4%]); lumbosacral spine 0.6% (95% CI [0.2-1.5%]); both
      abdomen and pelvis 0.3% (95% CI [0.1-1.1%]); both the abdomen and lumbosacral
      spine 0.6% (0.2-1.5%); both the pelvis and lumbosacral spine 0.1% (0.0-0.8%); all
      three regions - abdomen, pelvis and lumbosacral spine - 0.1% (0.0-0.8%).
      Conclusion: Automatic pairing of A/P CT has very low diagnostic yield for CSI in
      both the abdomen and pelvis. These data suggest a role for selective CT imaging
      protocols that image these regions individually instead of automatically as a
      pair.

PMID- 30202487
TI  - Sepsis Bundle Adherence Is Associated with Improved Survival in Severe Sepsis or
      Septic Shock.
AB  - Introduction: There have been conflicting data regarding the relationship between
      sepsis-bundle adherence and mortality. Moreover, little is known about how this
      relationship may be moderated by the anatomic source of infection or the location
      of sepsis declaration. Methods: This was a multi-center, retrospective,
      observational study of adult patients with a hospital discharge diagnosis of
      severe sepsis or septic shock. The study included patients who presented to one
      of three Los Angeles County Department of Health Services (DHS) full-service
      hospitals January 2012 to December 2014. The primary outcome of interest was the
      association between sepsis-bundle adherence and in-hospital mortality. Secondary
      outcome measures included in-hospital mortality by source of infection, and the
      location of sepsis declaration. Results: Among the 4,582 patients identified with
      sepsis, overall mortality was lower among those who received bundle-adherent care
      compared to those who did not (17.9% vs. 20.4%; p=0.035). Seventy-five percent
      (n=3,459) of patients first met sepsis criteria in the ED, 9.6% (n=444) in the
      intensive care unit (ICU) and 14.8% (n=678) on the ward. Bundle adherence was
      associated with lower mortality for those declaring in the ICU (23.0% adherent
      [95% confidence interval{CI} {16.8-30.5}] vs. 31.4% non-adherent [95% CI {26.4
      37.0}]; p=0.063), but not for those declaring in the ED (17.2% adherent [95% CI
      {15.8-18.7}] vs. 15.1% non-adherent [95% CI {13.0-17.5}]; p=0.133) or on the ward
      (24.8% adherent [95% CI {18.6-32.4}] vs. 24.4% non-adherent [95% CI {20.9-28.3}];
      p=0.908). Pneumonia was the most common source of sepsis (32.6%), and patients
      with pneumonia had the highest mortality of all other subsets receiving bundle
      non-adherent care (28.9%; 95% CI [25.3-32.9]). Although overall mortality was
      lower among those who received bundle-adherent care compared to those who did
      not, when divided into subgroups by suspected source of infection, a
      statistically significant mortality benefit to bundle-adherent sepsis care was
      only seen in patients with pneumonia. Conclusion: In a large public healthcare
      system, adherence with severe sepsis/septic shock management bundles was found to
      be associated with improved survival. Bundle adherence seems to be most
      beneficial for patients with pneumonia. The overall improved survival in patients
      who received bundle-adherent care was driven by patients declaring in the ICU.
      Adherence was not associated with lower mortality in the large subset of patients
      who declared in the ED, nor in the smaller subset of patients who declared in the
      ward.

PMID- 30202489
TI  - Emergency Department Visits for Sexual Assault by Emerging Adults: Is Alcohol a
      Factor?
AB  - Introduction: Emerging adults (18-25 years of age) are at increased risk for
      sexual assault. There is little Emergency Department (ED) data on sexual assaults
      that involve alcohol among this population. The purpose of this study was to
      analyze ED visits for sexual assault and determine if alcohol consumption by the
      patient was noted. Methods: This study was a retrospective chart review of
      patients aged 18-25 presenting to an ED in a college town over a four-year
      period. Extracted variables included age, gender, delay in seeking care, sexual
      assault nurse examiner (SANE) evaluation, and alcohol consumption by the patient.
      For analysis of alcohol use, cases were categorized as ages < 21 and >= 21.
      Results: There were 118 patients who presented to the ED from 2012 to 2015. The
      mean age of the cohort was 20 years, and almost 70% of visits were among those <
      21. Of those aged < 21, 74% reported alcohol consumption, in contrast to 48% of
      those >= 21 (p = 0.055). Of those reporting alcohol use, 36% were evaluated on
      the day of the assault compared to 61% of those not reporting alcohol (p=0.035).
      Conclusion: This study found that ED visits for sexual assault in emerging adults
      were more common in younger patients. Alcohol use occurred more frequently with
      patients under the legal drinking age, and presentation was also more likely to
      be delayed. The relationship between sexual assault and alcohol use should
      underscore primary prevention efforts in emerging adult populations.

PMID- 30202490
TI  - Emergency Medicine Physician Assistant (EMPA) Postgraduate Training Programs:
      Program Characteristics and Training Curricula.
AB  - Introduction: A growing number of formal postgraduate training programs have been
      established to provide emergency medicine physician assistants (EMPA) with the
      unique skills and knowledge to work in the emergency department (ED). The
      objective of this study was to provide an overview of the current state of EMPA
      postgraduate training and to describe program characteristics and curriculum
      components. Methods: We conducted a cross-sectional study of EMPA postgraduate
      training programs using data from websites and contacting individual programs to
      provide program characteristics and curriculum components. Variables collected
      included length of program, curriculum (e.g., clinical rotations, didactic
      experience, and research opportunities), size of program/number of trainees,
      affiliation with emergency medicine (EM) residency, geographic location, and
      salary. Results: We identified 29 EMPA postgraduate training programs in 17
      states, with at least one additional program in development. The mean length of
      EMPA training programs is 15 months (range 12-24 months). The most common non
      ED/elective rotations are orthopedics, ultrasound, anesthesiology, and trauma.
      The mean number of trainees per class is 3.46 (median 3, range 1-16 trainees); 27
      of 29 (93%) programs were in institutions that also had an EM residency program.
      The mean annual salary is $58,566 (range $43,000-90,000). Conclusion: EMPA
      postgraduate training programs have common characteristics and curriculum
      components despite a lack of a specialty-specific accrediting organization or
      certifying examination. The overall growth and current number of these programs
      merits further research focusing on whether standardized curricula, formal
      recognition, and accreditation should be developed.

PMID- 30202488
TI  - Emergency Department Computed Tomography Use for Non-traumatic Abdominal Pain:
      Minimal Variability.
AB  - Introduction: Variability in the use of computed tomography (CT) between
      providers in the emergency department (ED) suggests that CT is ordered on a
      provider rather than a patient level. We aimed to evaluate the variability of CT
      ordering practices for non-traumatic abdominal pain (NTAP) across physicians in
      the ED using patient-visit and physician-level factors. Methods: We conducted a
      retrospective study among 6,409 ED visits for NTAP from January 1 to December 31,
      2012, at a large, urban, academic, tertiary-care hospital. We used a two-level
      hierarchical logistic regression model to estimate inter-physician variation.
      Intraclass correlation coefficient (ICC) was calculated. Results: The
      hierarchical logistic regression analyses showed that patient-visit factors
      including younger age, arrival mode by ambulance, prior CT, >79 ED arrivals in
      the previous four hours, and ultrasound had statistically significant negative
      associations with physician CT ordering, while surgical team admission and white
      blood count (WBC) >12.5 K/millimeter cubed (mm3) had statistically significant
      positive associations with physician CT ordering. With physician-level factors,
      only physicians with >21 years experience after medical school graduation showed
      statistical significance negatively associated with physician CT ordering. Our
      data demonstrated increased CT ordering from the mean in only one out of 43
      providers (2.3%), which indicated limited variation across physicians to order
      CT. After adjusting for patient-visit and physician-level factors, the calculated
      ICC was 1.46%. Conclusion: We found minimal physician variability in CT ordering
      practices for NTAP. Patient-visit factors such as age, arrival mode, admission
      team, prior CT, ED arrivals in previous four hours, ultrasound, and WBC count
      were found to largely influence CT ordering practices.

PMID- 30202491
TI  - Ultrasound-guided Placement of Single-lumen Peripheral Intravenous Catheters in
      the Internal Jugular Vein.
AB  - Introduction: The peripheral internal jugular (IJ), also called the "easy IJ," is
      an alternative to peripheral venous access reserved for patients with difficult
      intravenous (IV) access. The procedure involves placing a single-lumen catheter
      in the IJ vein under ultrasound (US) guidance. As this technique is relatively
      new, the details regarding the ease of the procedure, how exactly it should be
      performed, and the safety of the procedure are uncertain. Our primary objective
      was to determine the success rate for peripheral IJ placement. Secondarily, we
      evaluated the time needed to complete the procedure and assessed for
      complications. Methods: This was a prospective, single-center study of US-guided
      peripheral IJ placement using a 2.5-inch, 18-gauge catheter on a convenience
      sample of patients with at least two unsuccessful attempts at peripheral IV
      placement by nursing staff. Peripheral IJ lines were placed by emergency medicine
      (EM) attending physicians and EM residents who had completed at least five IJ
      central lines. All physicians who placed lines for the study watched a 15-minute
      lecture about peripheral IJ technique. A research assistant monitored each line
      to assess for complications until the patient was discharged. Results: We
      successfully placed a peripheral IJ in 34 of 35 enrolled patients (97.1%). The
      median number of attempts required for successful cannulation was one
      (interquartile range (IQR): 1 to 2). The median time to successful line placement
      was 3 minutes and 6 seconds (IQR: 59 seconds to 4 minutes and 14 seconds). Two
      lines failed after placement, and one of the 34 successfully placed peripheral IJ
      lines (2.9%) had a complication - a local hematoma. There were, however, no
      arterial punctures or pneumothoraces. Although only eight of 34 lines were placed
      using sterile attire, there were no line infections. Conclusion: Our research
      adds to the growing body of evidence supporting US-guided peripheral internal
      jugular access as a safe and convenient procedure alternative for patients who
      have difficult IV access.

PMID- 30202492
TI  - Accuracy of Height Estimation Among Bystanders.
AB  - Introduction: High-risk mechanisms in trauma usually dictate certain treatment
      and evaluation in protocolized care. A 10-15 feet (ft) fall is traditionally
      cited as an example of a high-risk mechanism, triggering trauma team activations
      and costly work-ups. The height and other details of mechanism are usually
      reported by lay bystanders or prehospital personnel. This small observational
      study was designed to evaluate how accurate or inaccurate height estimation may
      be among typical bystanders. Methods: This was a blinded, prospective study
      conducted on the grounds of a community hospital. Four panels with lines
      corresponding to varying heights from 1-25 ft were hung within a building
      structure that did not have stories or other possibly confounding factors by
      which to judge height. The participants were asked to estimate the height of each
      line using a multiple-choice survey-style ballot. Participants were adult
      volunteers composed of various hospital and non-hospital affiliated persons, of
      varying ages and genders. In total, there were 96 respondents. Results: For
      heights equal to or greater than 15 ft, less than 50% of participants of each job
      description were able to correctly identify the height. When arranged into a
      scatter plot, as height increased, the likelihood to underestimate the correct
      height was evident, having a strong correlation coefficient (R=+0.926) with a
      statistically significant p value = <0.001. Conclusion: The use of vertical
      height as a predictor of injury severity is part of current practice in trauma
      triage. This data is often an estimation provided by prehospital personnel or
      bystanders. Our small study showed bystanders may not estimate heights accurately
      in the field. The greater the reported height, the less likely it is to be
      accurate. Additionally, there is a higher likelihood that falls from greater than
      15 ft may be underestimated.

PMID- 30202493
TI  - Preparing Osteopathic Students for the Single Graduate Medical Education
      Accreditation System: Evaluating Factors for Match Success in Emergency Medicine.
AB  - Introduction: With the development of and progression toward a single graduate
      medical education accreditation system combining the current Accreditation
      Council for Graduate Medical Education (ACGME) and American Osteopathic
      Association (AOA) residency programs, the total number of students competing for
      the same postgraduate training spots will continue to rise. Given this increasing
      competition for emergency medicine (EM) residency positions, understanding
      factors that contribute to match success is important to ensure a successful
      match for osteopathic medical students. Methods: Our anonymous survey to evaluate
      factors that led to a successful match was sent out to residents in current ACGME
      , AOA-, and dually-accredited programs via the AOA program director listserv and
      the Council of Residency Directors (CORD) e-mail listserv in 2017. Results: We
      had 218 responses. Responses showed that osteopathic graduates had less
      affiliation with EM residencies, their home institutions provided less
      information regarding standardized letters of evaluations (SLOE), and that
      successful osteopathic graduates seemed to learn about them while on EM elective
      rotations. These students also had less direct EM mentorship and were generally
      unsatisfied with the level of mentorship available. Osteopathic graduates in
      current ACGME programs were also more likely to have taken the United States
      Medical Licensing Examination compared to their AOA resident counterparts.
      Conclusion: Osteopathic medical schools can improve their graduates' chances of
      successfully matching in EM by establishing mentorship programs and educating
      their students early about SLOEs.

PMID- 30202494
TI  - Comment on "A Tactical Medicine After-action Report of the San Bernardino
      Terrorist Incident".

PMID- 30202495
TI  - Serum Lactate and Mortality in Emergency Department Patients with Cancer.
AB  - Introduction: Patients with malignancy represent a particular challenge for the
      emergency department (ED) given their higher acuity, longer ED length of stay,
      and higher admission rate. It is unknown if patients with malignancies and
      hyperlactatemia are at increased risk of mortality. If serum lactic acid could
      improve detection of at-risk patients with cancer, it would be useful in risk
      stratification. There is also little evidence that "alarm" values of serum
      lactate (such as >/=4 mmol/L) are appropriate for the population of patients with
      cancer. Methods: This was a continuous retrospective cohort study of
      approximately two years (2012-2014) at a single, tertiary hospital ED; 5,440
      patients had serum lactic acid measurements performed in the ED. Of the 5,440
      patients in whom lactate was drawn, 1,837 were cancer patients, and 3,603 were
      non-cancer patients. Cumulative unadjusted mortality (determined by hospital
      records and an external death tracking system) was recorded at one day, three
      days, seven days, and 30 days. We used logistic regression to examine the risk of
      mortality 30 days after the ED visit after adjusting for confounders. Results: In
      an unadjusted analysis, we found no statistically significant difference in the
      mortality of cancer vs. non-cancer patients at one day and three days.
      Significant differences in mortality were found at seven days (at lactate levels
      of <2 and 4+) and at 30 days (at all lactate levels) based on cancer status.
      After adjusting for age, gender, and acuity level, 30-day mortality rates were
      significantly higher at all levels of lactic acid (<2, 2-4, 4+) for patients with
      malignancy. Conclusion: When compared with non-cancer patients, cancer patients
      with elevated ED lactic acid levels had an increased risk of mortality at
      virtually all levels and time intervals we measured, although these differences
      only reached statistical significance in later time intervals (Day 7 and Day 30).
      Our results suggest that previous work in which lactate "cutoffs" are used to
      risk-stratify patients with respect to outcomes may be insufficiently sensitive
      for patients with cancer. Relatively low serum lactate levels may serve as a
      marker for serious illness in oncologic patients who present to the ED.

PMID- 30202496
TI  - Left Ventricular Assist Device Management in the Emergency Department.
AB  - The prevalence of patients living with a left ventricular assist device (LVAD) is
      rapidly increasing due to improvements in pump technology, limiting the adverse
      event profile, and to expanding device indications. To date, over 22,000 patients
      have been implanted with LVADs either as destination therapy or as a bridge to
      transplant. It is critical for emergency physicians to be knowledgeable of
      current ventricular assist devices (VAD), and to be able to troubleshoot
      associated complications and optimally treat patients with emergent pathology.
      Special consideration must be taken when managing patients with VADs including
      device inspection, alarm interpretation, and blood pressure measurement. The
      emergency physician should be prepared to evaluate these patients for cerebral
      vascular accidents, gastrointestinal bleeds, pump failure or thrombosis, right
      ventricular failure, and VAD driveline infections. Early communication with the
      VAD team and appropriate consultants is essential for emergent care for patients
      with VADs.

PMID- 30202497
TI  - A Risk Score to Predict Short-term Outcomes Following Emergency Department
      Discharge.
AB  - Introduction: The emergency department (ED) is an inherently high-risk setting.
      Risk scores can help practitioners understand the risk of ED patients for
      developing poor outcomes after discharge. Our objective was to develop two risk
      scores that predict either general inpatient admission or death/intensive care
      unit (ICU) admission within seven days of ED discharge. Methods: We conducted a
      retrospective cohort study of patients age > 65 years using clinical data from a
      regional, integrated health system for years 2009-2010 to create risk scores to
      predict two outcomes, a general inpatient admission or death/ICU admission. We
      used logistic regression to predict the two outcomes based on age, body mass
      index, vital signs, Charlson comorbidity index (CCI), ED length of stay (LOS),
      and prior inpatient admission. Results: Of 104,025 ED visit discharges, 4,638
      (4.5%) experienced a general inpatient admission and 531 (0.5%) death or ICU
      admission within seven days of discharge. Risk factors with the greatest point
      value for either outcome were high CCI score and a prolonged ED LOS. The C
      statistic was 0.68 and 0.76 for the two models. Conclusion: Risk scores were
      successfully created for both outcomes from an integrated health system,
      inpatient admission or death/ICU admission. Patients who accrued the highest
      number of points and greatest risk present to the ED with a high number of
      comorbidities and require prolonged ED evaluations.

PMID- 30202498
TI  - Impact of a Pharmacist-Driven Prothrombin Complex Concentrate Protocol on Time to
      Administration in Patients with Warfarin-associated Intracranial Hemorrhage.
AB  - Introduction: Advancements in the treatment of warfarin-associated intracranial
      hemorrhage (ICH) include the use of four-factor prothrombin complex concentrate
      (4F-PCC), which has demonstrated more rapid reversal of the international
      normalized ratio (INR) when compared with fresh frozen plasma. A pharmacist
      driven protocol for 4F-PCC was implemented within our institution, which allows
      for pharmacist approval of 4F-PCC in patients diagnosed with warfarin-associated
      ICH and an INR >=2. The pharmacist is responsible for determining the appropriate
      dose of 4F-PCC, preparation, bedside delivery, and order entry into the
      electronic medical record. Prior to implementation of the new protocol, the blood
      bank was responsible for 4F-PCC approval, dosing, product preparation, and
      arranging delivery with emergency department (ED) staff. The purpose of this
      study was to evaluate the impact of a pharmacist-driven protocol on time to 4F
      PCC administration in warfarin-associated ICH. Methods: We performed a
      retrospective review of consecutive patients who received 4F-PCC in a single ED
      from September 2015 through February 2017. Patients >=18 years old were eligible
      for inclusion based on three criteria: confirmed diagnosis of ICH; confirmed
      warfarin use; and INR >=2. Secondary outcomes included dose of 4F-PCC in
      concordance with INR and weight-based dosing recommendations and hospital
      protocol, as well as concomitant intravenous vitamin K administration. Results: A
      total of 48 patients met inclusion criteria for the study with 24 patients in
      each protocol group. The median time to administration of 4F-PCC in the
      pharmacist-driven protocol group was 35 minutes (interquartile range [IQR] [25
      62]; range, 11-133) compared with 70 minutes (IQR [34-89]; range, 14-244) in the
      pre-protocol group (p=0.034). We saw no differences for appropriate 4F-PCC dosing
      based on INR and patient weight between the two groups. Conclusion:
      Implementation of a pharmacist-driven protocol for 4F-PCC in the ED at our
      institution significantly reduced time to administration in patients presenting
      with warfarin-associated ICH.

PMID- 30202499
TI  - NHAMCS Validation of Emergency Severity Index as an Indicator of Emergency
      Department Resource Utilization.
AB  - Introduction: Triage systems play a vital role in emergency department (ED)
      operations and can determine how well a given ED serves its local population. We
      sought to describe ED utilization patterns for different triage levels using the
      National Hospital Ambulatory Medical Care Survey (NHAMCS) database. Methods: We
      conducted a multi-year secondary analysis of the NHAMCS database from 2009-2011.
      National visit estimates were made using standard methods in Analytics Software
      and Solutions (SAS, Cary, NC). We compared patients in the mid-urgency range in
      regard to ED lengths of stay, hospital admission rates, and numbers of tests and
      procedures in comparison to lower or higher acuity levels. Results: We analyzed
      100,962 emergency visits (representing 402,211,907 emergency visits nationwide).
      In 2011, patients classified as triage levels 1-3 had a higher number of
      diagnoses (5.5, 5.6 and 4.2, respectively) when compared to those classified as
      levels 4 and 5 (1.61 and 1.25). This group also underwent a higher number of
      procedures (1.0, 0.8 and 0.7, versus 0.4 and 0.4), had a higher ED length of stay
      (220, 280 and 237, vs. 157 and 135), and admission rates (32.2%, 32.3% and 15.5%,
      vs. 3.1% and 3.6%). Conclusion: Patients classified as mid-level (3) triage
      urgency require more resources and have higher indicators of acuity as those in
      triage levels 4 and 5. These patients' indicators are more similar to those
      classified as triage levels 1 and 2.

PMID- 30202501
TI  - Transcutaneous Electrical Nerve Stimulation (TENS) in the Emergency Department
      for Pain Relief: A Preliminary Study of Feasibility and Efficacy.
AB  - Introduction: Given the high rates of opioid addiction and overdose in the United
      States, non-opioid means of treating pain are increasingly needed. Transcutaneous
      electrical nerve stimulation (TENS) therapy is an effective non-opioid modality
      for treating pain, but has not yet been routinely used in emergency department
      (ED) settings. In this study we asked the following questions: Are TENS units a
      feasible treatment for pain in the ED? How effective are TENS units for the
      management of pain in a general ED population? Methods: At our institution, we
      performed a pilot study using TENS units for pain. Patients in the ED were given,
      at the discretion of the ED provider, TENS units for the treatment of pain.
      Patients could be included for acute or chronic pain on whatever part of the body
      that was safe to use with TENS. Results: A chart review of patients receiving
      TENS units in the ED (n=110) revealed that TENS was useful in relieving pain,
      along with other treatments, in 99% of cases. When surveyed, 83% of patients
      reported a functional improvement while using the TENS, and 100% of patients
      would recommend a TENS unit to a family or friend. When surveyed, 100% of ED
      staff observed that TENS units were effective in treating pain for patients, and
      97% would want to use them if they themselves were patients. Conclusion: Overall,
      in this small pilot study, TENS units appeared to be effective in our ED for
      reducing pain, when added to standard treatment. Additional studies are needed to
      determine which conditions are most responsive to TENS therapy, and the magnitude
      of pain reduction when used alone.

PMID- 30202500
TI  - The Misunderstood Coagulopathy of Liver Disease: A Review for the Acute Setting.
AB  - The international normalized ratio (INR) represents a clinical tool to assess the
      effectiveness of vitamin-K antagonist therapy. However, it is often used in the
      acute setting to assess the degree of coagulopathy in patients with hepatic
      cirrhosis or acute liver failure. This often influences therapeutic decisions
      about invasive procedures or the need for potentially harmful and unnecessary
      transfusions of blood product. This may not represent a best-practice or evidence
      based approach to patient care. The author performed a review of the literature
      related to the utility of INR in cirrhotic patients using several scientific
      search engines. Despite the commonly accepted dogma that an elevated INR in a
      cirrhotic patient corresponds with an increased hemorrhagic risk during the
      performance of invasive procedures, the literature does not support this belief.
      Furthermore, the need for blood-product transfusion prior to an invasive
      intervention is not supported by the literature, as this practice increases the
      risk of complications associated with a patient's hospital course. Many
      publications ranging from case studies to meta-analyses refute this evidence and
      provide examples of thrombotic events despite elevated INR values. Alternative
      methods, such as thromboelastogram, represent alternate means of assessing in
      vivo risk of hemorrhage in patients with acute or chronic liver disease in real
      time in the acute setting.

PMID- 30202502
TI  - Emergency Providers' Pain Management in Patients Transferred to Intensive Care
      Unit for Urgent Surgical Interventions.
AB  - Introduction: Pain is the most common complaint for an emergency department (ED)
      visit, but ED pain management is poor. Reasons for poor pain management include
      providers' concerns for drug-seeking behaviors and perceptions of patients'
      complaints. Patients who had objective findings of long bone fractures were more
      likely to receive pain medication than those who did not, despite pain
      complaints. We hypothesized that patients who were interhospital-transferred from
      an ED to an intensive care unit (ICU) for urgent surgical interventions would
      display objective pathology for pain and thus receive adequate pain management at
      ED departure. Methods: This was a retrospective study at a single, quaternary
      referral, academic medical center. We included non-trauma adult ED patients who
      were interhospital-transferred and underwent operative interventions within 12
      hours of ICU arrival between July 2013 and June 2014. Patients who had incomplete
      ED records, required invasive mechanical ventilation, or had no pain throughout
      their ED stay were excluded. Primary outcome was the percentage of patients at ED
      departure achieving adequate pain control of <= 50% of triage level. We performed
      multivariable logistic regression to assess association between demographic and
      clinical variables with inadequate pain control. Results: We included 112
      patients from 39 different EDs who met inclusion criteria. Mean pain score at
      triage and ED departure was 8 (standard deviation 8 and 5 [3]), respectively.
      Median of total morphine equivalent unit (MEU) was 7.5 [5-13] and MEU/kg total
      body weight (TBW) was 0.09 [0.05-0.16] MEU/kg, with median number of pain
      medication administration of 2 [1-3] doses. Time interval from triage to first
      narcotic dose was 61 (35-177) minutes. Overall, only 38% of patients achieved
      adequate pain control. Among different variables, only total MEU/kg was
      associated with significant lower risk of inadequate pain control at ED departure
      (adjusted odds ratio = 0.22; 95% confidence interval = 0.05-0.92, p = 0.037).
      Conclusion: Pain control among a group of interhospital-transferred patients
      requiring urgent operative interventions, was inadequate. Neither demographic nor
      clinical factors, except MEU/kg TBW, were shown to associate with poor pain
      management at ED departure. Emergency providers should consider more effective
      strategies, such as multimodal analgesia, to improve pain management in this
      group of patients.

PMID- 30202503
TI  - The Effect of Point-of-Care Testing at Triage: An Observational Study in a
      Teaching Hospital in Saudi Arabia.
AB  - Introduction: Prolonged waiting times during episodes of emergency department
      (ED) crowding are associated with poor outcomes. Point-of-care testing (POCT) at
      ED triage prior to physician evaluation may help identify critically ill
      patients. We studied the impact of ED POCT in a single ED with a high degree of
      crowding for patients with high-risk complaints who were triaged as non
      critically ill. Methods: We conducted the study from April-July 2017 at King
      Abdulaziz University (KAU) Hospital in Jeddah, Saudi Arabia. Patients with one of
      seven complaints received triage POCT. The primary outcome was whether POCT
      results at triage resulted in immediate transfer of the patient from the waiting
      room into the ED. Secondary outcomes were whether the triage nurse felt that the
      POCT results were useful, and whether triage POCT changed triage acuity. We used
      simple descriptive statistics to summarize the data. Results: A total of 94
      patients were enrolled and received i-STAT(r) POCT. The most common symptoms and
      triage protocols were for chest pain (42%), abdominal pain (31%), and shortness
      of breath (22%). In 11 cases (12%), care was changed as a result of triage POCT.
      In 12 cases (13%), triage level was changed. The triage nurse found POCT helpful
      in 93% of cases. Conclusion: In this ED, triage POCT was a helpful adjunct at ED
      triage and resulted in immediate care (transfer to an ED room) in one in eight
      cases. Therefore, POCT at triage may be a useful adjunct to improve patient
      safety, particularly in crowded EDs.

PMID- 30202505
TI  - Erratum: This Article Corrects: "Systemwide Clinical Ultrasound Program
      Development: An Expert Consensus Model".
AB  - [This corrects the article on p. 649 in vol. 19, PMID: 30013699.].

PMID- 30202504
TI  - Universal Health Coverage in Rural Ecuador: A Cross-sectional Study of Perceived
      Emergencies.
AB  - Introduction: In many low- and middle-income countries emergency care is provided
      anywhere in the health system; however, no studies to date have looked at which
      providers are chosen by patients with perceived emergencies. Ecuador has
      universal health coverage that includes emergency care. However, earlier research
      indicates that patients with emergencies tend to seek private care. Our primary
      research questions were these: What is the scope of perceived emergencies?; What
      is their nature?; and What is the related healthcare-seeking behavior? Secondary
      objectives were to study determinants of healthcare-seeking behavior, compare
      health expenditure with expenditure from the past ordinary illness, and measure
      the prevalence of catastrophic health expenditure related to perceived
      emergencies. Methods: We conducted a cross-sectional survey of 210 households in
      a rural region of northwestern Ecuador. The households were sampled with two
      stage cluster sampling and represent an estimated 20% of the households in the
      region. We used two structured, pretested questionnaires. The first questionnaire
      collected demographic and economic household data, expenditure data on the past
      ordinary illness, and presented our definition of perceived emergency. The second
      recorded the number of emergency events, symptoms, further case description,
      healthcare-seeking behavior, and health expenditure, which was defined as being
      catastrophic when it exceeded 40% of a household's ability to pay. Results: The
      response rate was 85% with a total of 74 reported emergency events during the
      past year (90/1,000 inhabitants). We further analyzed the most recent event in
      each household (n=54). Private, for-profit providers, including traditional
      healers, were chosen by 57.4% (95% confidence interval [CI] [44-71%]). Public
      providers treated one third of the cases. The mean health expenditure per event
      was $305.30 United States dollars (USD), compared to $135.80 USD for the past
      ordinary illnesses. Catastrophic health expenditure was found in 24.4% of
      households. Conclusion: Our findings suggest that the provision of free health
      services may not be sufficient to reach universal health coverage for patients
      with perceived emergencies. Changes in the organization of public emergency
      departments and improved financial protection for emergency patients may improve
      the situation.

PMID- 30202506
TI  - Rapid diagnosis of Zika virus through saliva and urine by Loop-mediated
      isothermal amplification (LAMP).
AB  - Background: Zika virus (ZIKV) is a single-stranded RNA virus and member of the
      Flaviviridae family. Recent studies have reported that saliva can be an important
      alternative to detect ZIKV. Saliva requires less processing than blood greatly
      simplifying the assay. Loop-mediated Isothermal Amplification (LAMP) is a rapid
      assay that detects nucleic acids, including ZIKV RNA. Aim: The aim of this study
      was to evaluate the efficacy of saliva and urine to diagnose ZIKV infection in
      subjects during the acute phase, through ZIKV RNA detection by LAMP. Method: A
      total of 131 samples (68 saliva and 63 urine samples) from 69 subjects in the
      acute phase of ZIKV infection, and confirmed positive for ZIKV by blood analysis
      through real time-PCR, were collected and analyzed by Reverse Transcriptase Loop
      mediated Isothermal Amplification (RT-LAMP). Results: From the 68 saliva samples,
      45 (66.2%) were positive for ZIKV with an average time to positivity (Tp) of 13.5
      min, and from the 63 urine samples, 25 (39.7%) were positive with the average Tp
      of 15.8 min. Saliva detected more samples (p = 0.0042) and had faster Tp (p =
      0.0176) as compared with urine. Conclusion: Saliva proved to be a feasible
      alternative to diagnose ZIKV infection during the acute phase by LAMP.

PMID- 30202507
TI  - Diabetes-related foot disorders among adult Ghanaians.
AB  - Background: Diabetic foot remains a challenge in most low-middle-income countries
      (LMICs). A severe deficit in data exists on them in sub-Saharan Africa (SSA). Up
      to-date data on the longitudinal trajectories and determinants can provide a
      benchmark for reducing diabetic foot complications in SSA. Objective: The primary
      objective of this study was to estimate trends in the incidence of diabetic foot
      and determine predictors in an adult Ghanaian diabetes cohort. Design: The study
      is a retrospective longitudinal study over a 12 year period. Methods: We applied
      Poisson regression analysis and Cox proportional hazard models to demographic and
      clinical information obtained from patients who enrolled in a diabetes specialist
      clinic in Ghana from 2005 to 2016 to identify longitudinal trends in incidence
      and predictors of diabetic foot. Results: The study comprised 7383 patients
      (63.8% female, mean follow-up duration: 8.6 years). The mean incidence of foot
      disorders was 8.39% (5.27% males and 3.12% females). An increase in the incidence
      of diabetic foot ranging from 3.25% in 2005 to 12.57% in 2016, p < 0.001, was
      determined. Diabetic foot, with adjusted hazard ratio (HR; 95% confidence
      interval (CI)), was predicted by disease duration, that is, for every 5-year
      increase in diabetes duration: 2.56 (1.41-3.06); male gender: 3.51 (1.41-3.06);
      increased body mass index (BMI), that is, for every 5 kg/m2: 3.20 (2.51-7.52);
      poor glycaemic control, that is, for every percentage increase in HbA1c: 1.11
      (1.05-2.25), hypertension: 1.14 (1.12-3.21); nephropathy: 1.15 (1.12-3.21); and
      previous foot disorders: 3.24 (2.12-7.21). Conclusions: We have found a trend
      towards an increased incidence of diabetic foot in an outpatient tertiary
      diabetes setting in Ghana. Systemic and individual-level factors aimed at
      preventive foot screening as well as vascular risk factor control should be
      intensified in diabetic patients in Ghana and other LMICs. Abbreviations: BMI:
      Body Mass Index, BP: Blood Pressure, CI: Confidence Interval, HR: Hazard Ratio,
      HbA1c: Glycated Hemoglobin, PAD: Peripheral Arterial Disease, NCDs: Non
      Communicable Disease, SSA: Sub Saharan Africa.

PMID- 30202508
TI  - The impact of robotic intervention on joint attention in children with autism
      spectrum disorders.
AB  - Background: A growing body of anecdotal evidence indicates that the use of robots
      may provide unique opportunities for assisting children with autism spectrum
      disorders (ASD). However, previous studies investigating the effects of
      interventions using robots on joint attention (JA) in children with ASD have
      shown insufficient results. The robots used in these studies could not turn their
      eyes, which was a limitation preventing the robot from resembling a human agent.
      Methods: We compared the behavior of children with ASD with that of children with
      typical development (TD) during a JA elicitation task while the children
      interacted with either a human or a robotic agent. We used the robot "CommU,"
      which has clear eyes and can turn its eyes, for the robotic intervention. The age
      range of the participants was limited to 5-6 years. Results: Sixty-eight
      participants participated in this study, including 30 (10 females and 20 males)
      children with ASD and 38 (13 females and 25 males) children with TD. The
      participants were randomly assigned to one of the following two groups: the
      robotic intervention group or the control group. JA in the children with ASD was
      better during the robotic intervention than during the human agent intervention.
      These children exhibited improved performance in the JA task with human after
      interacting with the robot CommU. JA was differentially facilitated by the human
      and robotic agents between the ASD and TD children. Conclusions: The findings of
      this study significantly contribute to the literature on the impact of robots on
      JA and provide information regarding the suitability of specific robot types for
      therapeutic use.

PMID- 30202509
TI  - Chasing Animals With Split Attention: Are Animals Prioritized in Visual Tracking?
AB  - Some evolutionary psychologists have hypothesized that animals have priority in
      human attention. That is, they should be detected and selected more efficiently
      than other types of objects, especially man-made ones. Such a priority mechanism
      should automatically deploy more attentional resources and dynamic monitoring
      toward animal stimuli than nonanimals. Consequently, we postulated that
      variations of the multiple object or identity tracking and multiple event
      monitoring tasks should be particularly suitable paradigms for addressing the
      animate monitoring hypothesis, given their dynamic properties and dependency on
      divided attention. We used images of animals and artifacts and found neither a
      substantial sign of improvement in tracking the positions associated with animal
      stimuli nor a significant distracting effect of animals. We also failed to
      observe a significant prioritization in orders of response for positions
      associated with animals. While we observed an advantage for animals in event
      monitoring, this appeared to be dependent on properties of the task, as confirmed
      in further experiments. Moreover, we observed a small but inconclusive advantage
      for animals in identity accuracy. Thus, under certain conditions, some bias
      toward animals could be observed, but the evidence was weak and inconclusive. To
      conclude, effect sizes were generally small and not conclusively in favor of the
      expected attentional bias for animals. We found moderate to strong evidence that
      images of animals do not improve positional tracking, do not act as more
      effective distractors, are not selected prior to artifacts in the response phase,
      and are not easier to monitor for changes in size.

PMID- 30202511
TI  - An Introduction to the Special Issue "Seeing Colors".

PMID- 30202510
TI  - The Role of Visual Information in Body Size Estimation.
AB  - The conscious representation of our physical appearance is important for many
      aspects of everyday life. Here, we asked whether different visual experiences of
      our bodies influence body width estimates. In Experiment 1, width estimates of
      three body parts (foot, hips, and shoulders) without any visual access were
      compared to estimates with visual feedback available in a mirror or from a first
      person perspective. In the no visual access and mirror condition, participants
      additionally estimated their head width. There was no influence of viewing
      condition on body part width estimates. Consistent with previous research, all
      body part widths were overestimated with greater overestimation of hip and head
      width. In Experiment 2, participants estimated the size of unfamiliar
      noncorporeal objects to test whether this overestimation was partially due to the
      metric body size estimation method or our experimental conditions. Object width
      was overestimated with visual feedback in a mirror available as compared to when
      directly looking at the object, but only for objects placed at shoulder and head
      height. We conclude that at least some of the overestimation of body part width
      seems to be body specific and occurs regardless of the visual information
      provided about the own body.

PMID- 30202512
TI  - Biomimetic oyster shell-replicated topography alters the behaviour of human
      skeletal stem cells.
AB  - The regenerative potential of skeletal stem cells provides an attractive prospect
      to generate bone tissue needed for musculoskeletal reparation. A central issue
      remains efficacious, controlled cell differentiation strategies to aid
      progression of cell therapies to the clinic. The nacre surface from Pinctada
      maxima shells is known to enhance bone formation. However, to date, there is a
      paucity of information on the role of the topography of P. maxima surfaces, nacre
      and prism. To investigate this, nacre and prism topographical features were
      replicated onto polycaprolactone and skeletal stem cell behaviour on the surfaces
      studied. Skeletal stem cells on nacre surfaces exhibited an increase in cell
      area, increase in expression of osteogenic markers ALP (p < 0.05) and OCN (p <
      0.01) and increased metabolite intensity (p < 0.05), indicating a role of nacre
      surface to induce osteogenic differentiation, while on prism surfaces, skeletal
      stem cells did not show alterations in cell area or osteogenic marker expression
      and a decrease in metabolite intensity (p < 0.05), demonstrating a distinct role
      for the prism surface, with the potential to maintain the skeletal stem cell
      phenotype.

PMID- 30202513
TI  - Periostin expression in neoplastic and non-neoplastic diseases of bone and joint.
AB  - Background: Periostin is a matricellular protein that is expressed in bone and
      joint tissues. To determine the expression of periostin in primary bone tumours
      and to assess whether it plays a role in tumour progression, we carried out
      immunohistochemistry and ELISA for periostin in a range of neoplastic and non
      neoplastic bone and joint lesions. Methods: 140 formalin-fixed paraffin-embedded
      sections of bone tumours and tumour-like lesions were stained by an indirect
      immunoperoxidase technique with a polyclonal anti-periostin antibody. Periostin
      expression was also assessed in rheumatoid arthritis (RA) and non-inflammatory
      osteoarthritis (OA) synovium and synovial fluid immunohistochemistry and ELISA
      respectively. Results: Periostin was most strongly expressed in osteoid/woven
      bone of neoplastic and non-neoplastic bone-forming lesions, including
      osteoblastoma, osteosarcoma, fibrous dysplasia, osteofibrous dysplasia, fracture
      callus and myositis ossificans, and mineralised chondroid matrix/woven bone in
      chondroblastoma and clear cell chondrosarcoma. Reactive host bone at the edge of
      growing tumours, particularly in areas of increased vascularity and fibrosis,
      also stained strongly for periostin. Vascular elements in RA synovium strongly
      expressed periostin, and synovial fluid levels of periostin were higher in RA
      than OA. Conclusions: In keeping with its known role in modulating the synthesis
      of collagen and other extracellular matrix proteins in bone, strong periostin
      expression was noted in benign and malignant lesions forming an osteoid or
      osteoid-like matrix. Periostin was also noted in other bone tumours and was found
      in areas of reactive bone and increased vascularity at the edge of growing
      tumours, consistent with its involvement in tissue remodelling and angiogenesis
      associated with tumour progression.

PMID- 30202514
TI  - Inhibition of STAT3 in gastric cancer: role of pantoprazole as SHP-1 inducer.
AB  - Background: We investigated the inhibitory effect of pantoprazole on signal
      transducer and activator of transcription 3 (STAT3) activity and invasiveness of
      gastric adenocarcinoma cells, and the role of SH2-containing protein tyrosine
      phosphatase 1 (SHP-1) in mediating role. Methods: We used AGS and MKN-28 cells
      because of reduced SHP-1 and preserved p-STAT3 expression. Western blot, wound
      closure assay, Matrigel invasion assay and 3-D culture invasion assay were
      performed. Pharmacologic inhibitor of SHP-1 and siRNA were used for validation of
      the role of SHP-1. Results: We observed that pantoprazole at 40, 80, and 160
      MUg/ml upregulated SHP-1 and downregulated p-STAT3 expression in a dose-dependent
      manner in AGS and MKN-28 cells. Furthermore, pantoprazole significantly
      downregulated mesenchymal markers (Snail1 and vimentin), upregulated epithelial
      marker (E-cadherin), and inhibited migration and invasion of AGS and MKN-28
      cells. To validate the role of SHP-1 in inhibition of STAT3 activity by
      pantoprazole in gastric cancer cells, we performed pharmacologic inhibition
      (pervanadate) or knockdown of SHP-1 before pantoprazole treatment, which
      significantly attenuated the suppression of p-STAT3 and anti-migration and
      invasion effect by pantoprazole in AGS cells. In xenograft tumor model, tumor
      volume was significantly reduced by intraperitoneal injection of pantoprazole,
      with upregulation of SHP-1 and downregulation of p-STAT3, which were attenuated
      by concomitant injection of pervanadate. Conclusion: Our data suggest that the
      inhibitory effect of pantoprazole on cellular migration and invasion might be
      through inducing SHP-1 in gastric cancer cells.

PMID- 30202515
TI  - A visual representation of cattle movement in Ireland during 2016.
AB  - The aim of this study was to create a clear visual representation of the live
      movements of cattle in the Republic of Ireland over the course of the year 2016.
      The animation created can be viewed online: https://youtu.be/PTCdPMnenBw This
      animation was created to be a communication tool to enable stakeholders to
      appreciate the extent of high risk cattle movements (farm to farm, farm to market
      to farm) in the Republic of Ireland and to highlight the potential role that
      these movements may play in the spread of infectious diseases of cattle in
      Ireland from one farm to another.

PMID- 30202516
TI  - Comparison of dextran and albumin on blood coagulation in patients undergoing
      major gynaecological surgery.
AB  - Background: Hydroxyethyl starches have been withdrawn from the European market.
      In Sweden, dextran was the main colloid until 2000, when starches overtook the
      market. After the recent 6S-trial, it was suggested that dextran could be
      reinstituted, but concerns for greater coagulopathy, bleeding and anaphylaxis
      still remain. An experimental study from our department indicated that isovolemic
      substitution of dextran-70 did not derange the von Willebrand function more than
      albumin 5%, considering the fact that dextran is hyperoncotic in comparison to
      albumin 5% and, therefore, induces a greater plasma volume expansion and thereby
      a greater dilutional coagulopathy. Methods: Eighteen patients undergoing major
      gynaecological surgery were assigned to receive either 5% albumin or 6% dextran
      70 with 9 patients in each group. Standard coagulation tests, including
      prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen
      and platelet count, viscoelastic coagulation test thromboelastometry (ROTEM) and
      the Multiplate platelet aggregation test were used to test for coagulation
      defects at different time points perioperatively. Blood loss, blood loss
      replacement data and haemodynamic parameters were retrieved from anaesthetic and
      postoperative charts. A local departmental fluid and transfusion/infusion
      protocol assured haemoglobin > 90 g/l and mean arterial pressure > 65 mmHg with
      Ringer's acetate in addition to the colloid use. Results: There were no
      differences in demographic data between the groups. The tissue factor-activated
      (EXTEM) clot-structure parameter ROTEM A10 was decreased significantly in the
      dextran group as compared to the albumin group after the infusion of 500 ml of
      either colloid solution. The PT and aPTT were significantly prolonged, and the
      platelet count decreased postoperatively in the dextran group, whereas albumin
      only deranged fibrinogen levels as compared to preoperative levels. There were no
      differences in Multiplate platelet aggregometry, amount of haemorrhage or
      transfusion of blood components between the groups. Conclusions: Standard plasma
      based coagulation tests, platelet count and whole blood viscoelastic clot
      structure are affected by 6% dextran-70 to a greater extent than by 5% albumin,
      but platelet aggregation is not. Future studies should use more advanced
      haemodynamic monitoring to assess isovolemic plasma volume expansion with dextran
      and whether this affects haemostasis to a lesser degree.

PMID- 30202519
TI  - Validation studies for population-based intervention coverage indicators: design,
      analysis, and interpretation.
AB  - Background: Population-based intervention coverage indicators are widely used to
      track country and program progress in improving health and to evaluate health
      programs. Indicator validation studies that compare survey responses to a "gold
      standard" measure are useful to understand whether the indicator provides
      accurate information. The Improving Coverage Measurement (ICM) Core Group has
      developed and implemented a standard approach to validating coverage indicators
      measured in household surveys, described in this paper. Methods: The general
      design of these studies includes measurement of true health status and
      intervention receipt (gold standard), followed by interviews with the individuals
      observed, and a comparison of the observations (gold standard) to the responses
      to survey questions. The gold standard should use a data source external to the
      respondent to document need for and receipt of an intervention. Most frequently,
      this is accomplished through direct observation of clinical care, and/or use of a
      study-trained clinician to obtain a gold standard diagnosis. Follow-up interviews
      with respondents should employ standard survey questions, where they exist, as
      well as alternative or additional questions that can be compared against the
      standard household survey questions. Results: Indicator validation studies should
      report on participation at every stage, and provide data on reasons for non
      participation. Metrics of individual validity (sensitivity, specificity, area
      under the receiver operating characteristic curve) and population-level validity
      (inflation factor) should be reported, as well as the percent of survey responses
      that are "don't know" or missing. Associations between interviewer and
      participant characteristics and measures of validity should be assessed and
      reported. Conclusions: These methods allow respondent-reported coverage measures
      to be validated against more objective measures of need for and receipt of an
      intervention, and should be considered together with cognitive interviewing,
      discriminative validity, or reliability testing to inform decisions about which
      indicators to include in household surveys. Public health researchers should
      assess the evidence for validity of existing and proposed household survey
      coverage indicators and consider validation studies to fill evidence gaps.

PMID- 30202518
TI  - Quality of oxytocin ampoules available in health care facilities in the
      Democratic Republic of Congo: an exploratory study in five provinces.
AB  - Background: Oxytocin injection is the first line therapy for the prevention and
      treatment of postpartum haemorrhage (PPH), the leading cause of maternal
      mortality. Currently access to high quality oxytocin in low and middle-income
      countries (LMICs) is compromised by variable manufacturing quality and the
      requirement for cold chain supply and storage to prevent product deterioration.
      Previous studies of oxytocin ampoules sampled from Africa, the region with
      highest maternal mortality rates, indicate that over half do not contain the
      specified amount of oxytocin. International efforts continue to further
      understand the issues relating to oxytocin quality in LMICs and this study is the
      first to assess oxytocin quality in the Democratic Republic of Congo (DRC), a
      country that bears one of the highest global rates of maternal mortality (693
      maternal deaths per 100 000 live births). Importantly, the study methodology
      includes the use of investigative analytical techniques to understand the cause
      of quality deficiencies and inform remedial measures. Methods: The study involved
      sampling of oxytocin injection ampoules from public and private health care
      facilities (n = 15) in urban and rural areas within five provinces of the DRC.
      Where available, each sample comprised 20 ampoules of oxytocin injection (10
      IU/mL) with smaller numbers collected where supplies were limited. Sample
      collection used overt sampling and mystery shopper approaches, as appropriate.
      Analysis of ampoules for oxytocin content and known degradation products utilised
      validated HPLC and LCMS methods, respectively. Sterility testing was conducted in
      accordance with the United States Pharmacopeia monograph. Results: Eighty percent
      of ampoules collected contained less than 90% of the specified content. Known
      degradation products of oxytocin were identified, indicating likely exposure to
      elevated temperatures post-manufacture. All samples contained an unknown impurity
      at a level of approximately 12.3% (8.0-20.5%) of the oxytocin main band peak. No
      samples failed sterility testing. Conclusions: There is evidence of a high
      prevalence of poor quality oxytocin ampoules in health facilities in the DRC
      likely resulting from both manufacturing quality issues and uncontrolled storage.
      A more comprehensive post-marketing surveillance study of oxytocin quality is
      warranted.

PMID- 30202517
TI  - Feasibility of engaging "Village Doctors" in the Community-based Integrated
      Management of Childhood Illness (C-IMCI): experience from rural Bangladesh.
AB  - Background: Informal health care providers particularly "village doctors" are the
      first point of care for under-five childhood illnesses in rural Bangladesh. We
      engaged village doctors as part of the Multi-Country Evaluation (MCE) of
      Integrated Management of Childhood Illness (IMCI) and assessed their management
      of sick under-five children before and after a modified IMCI training,
      supplemented with ongoing monitoring and supportive supervision. Methods: In 2003
      2004, 144 village doctors across 131 IMCI intervention villages in Matlab
      Bangladesh participated in a two-day IMCI training; 135 of which completed pre-
      and post-training evaluation tests. In 2007, 38 IMCI-trained village doctors
      completed an end-of-project knowledge retention test. Village doctor prescription
      practices for sick under-five children were examined through household surveys,
      and routine monitoring visits. In-depth interviews were done with mothers seeking
      care from village doctors. Results: Village doctors' knowledge on the assessment
      and management of childhood illnesses improved significantly after training;
      knowledge of danger signs of pneumonia and severe pneumonia increased from 39% to
      78% (P < 0.0001) and from 17% to 47% (P < 0.0001) respectively. Knowledge on the
      correct management of severe pneumonia increased from 62% to 84% (P < 0.0001),
      and diarrhoea management improved from 65% to 82% (P = 0.0005). Village doctors
      retained this knowledge over three years except for home management of pneumonia.
      No significant differences were observed in prescribing practices for diarrhoea
      and pneumonia management between trained and untrained village doctors. Village
      doctors were accessible to communities; 76% had cell phones; almost all attended
      home calls, and did not charge consultation fees. Nearly all (91%) received
      incentives from pharmaceutical representatives. Conclusions: Village doctors have
      the capacity to learn and retain knowledge on the appropriate management of under
      five illnesses. Training alone did not improve inappropriate antibiotic
      prescription practices. Intensive monitoring and efforts to target key actors
      including pharmaceutical companies, which influence village doctors dispensing
      practices, and implementation of mechanisms to track and regulate these providers
      are necessary for future engagement in management of under-five childhood
      illnesses.

PMID- 30202520
TI  - Epidemiology and microbiology of Gram-positive bloodstream infections in a
      tertiary-care hospital in Beijing, China: a 6-year retrospective study.
AB  - Background: Gram-positive bacterial bloodstream infections (BSIs) are serious
      diseases associated with high morbidity and mortality. The following study
      examines the incidence, clinical characteristics and microbiological features,
      drug resistance situations and mortality associated with Gram-positive BSIs at a
      large Chinese tertiary-care hospital in Beijing, China. Methods: A retrospective
      cohort study of patients with Gram-positive BSIs was performed between January 1,
      2011, and June 31, 2017, at the Chinese People's Liberation Army General
      Hospital. The patients' data were collected and included in the reviewing
      electronic medical records. Results: A total of 6887 episodes of Gram-positive
      BSIs occurred among 4275 patients over 6 years, and there were 3438 significant
      BSI episodes 69% of these cases were healthcare-associated, while 31% were
      community-associated. The overall incidence of Gram-positive BSIs fluctuated from
      7.26 to 4.63 episodes per 1000 admissions over 6 years. Malignancy was the most
      common comorbidity and indwelling central intravenous catheter was the most
      common predisposing factor for BSI. Staphylococci were the major pathogen
      (65.5%), followed by Enterococcus spp:(17.5%), Streptococcus spp.(7.1%) and other
      bacterial pathogens (9.9%). The resistance rates of Staphylococci and E.faecium
      to penicillins were more than 90%. the vancomycin-resistant isolates were E.
      faecium (4.1%) and staphylococcus epidermidis (0.13%); and only E.faecalis and
      E.faecium showed resistance to linezolid (3.8% and 3.1%). Between 2011 and 2017,
      the overall mortality of Gram-positive BSIs decreased from 6.27 to 4.75% (X2 =
      0.912, p = 0.892). Neverthess, the mortality in the ICU decreased from 60.46 to
      47.82%, while in the general ward it increased from 39.54 to 52.18%. Conclusions:
      The morbidity and mortality of Gram-positive BSIs have showed downward trends.
      Vancomycin and linezolid are still consider the best treatment for patients with
      Gram-positive BSIs.

PMID- 30202521
TI  - Chlorhexidine-coated surgical gloves influence the bacterial flora of hands over
      a period of 3 hours.
AB  - Background: The risk of SSI increases in the presence of foreign materials and
      may be caused by organisms with low pathogenicity, such as skin flora derived
      from hands of surgical team members in the event of a glove breach. Previously,
      we were able to demonstrate that a novel antimicrobial surgical glove coated
      chlorhexidine-digluconate as the active ingredient on its inner surface was able
      to suppress surgeons' hand flora during operative procedures by a magnitude of
      1.7 log10 cfu/mL. Because of the clinical design of that study, we were not able
      to measure the full magnitude of the possible antibacterial suppression effect of
      antimicrobial gloves over a full 3 h period. Methods: The experimental procedure
      followed the method for assessment of the 3-h effects of a surgical hand rub's
      efficacy to reduce the release of hand flora as described in the European Norm EN
      12791. Healthy volunteers tested either an antimicrobial surgical glove or non
      antimicrobial surgical latex gloves in a standardized laboratory-based experiment
      over a wear time of 3 h. Results: Wearing antimicrobial surgical glove after a
      surgical hand rub with 60% (v/v) n-propanol resulted in the highest 3-h reduction
      factor of 2.67 log10. Non-antimicrobial surgical gloves demonstrated
      significantly lower (p <= 0.01) 3-h reduction factors at 1.96 log10 and 1.68
      log10, respectively. Antibacterial surgical gloves are able to maintain a
      sustainable bacterial reduction on finger tips in a magnitude of almost 3 log10
      (log10 2.67 cfu) over 3 h wear time. Conclusion: It was demonstrated that wear of
      an antibacterial surgical glove coated with chlorhexidine-digluconate is able to
      suppress resident hand flora significantly over a period of 3-h.

PMID- 30202523
TI  - Growing older with post-polio syndrome: Social and quality-of-life implications.
AB  - Objectives: To understand the quality-of-life implications for post-polio
      syndrome survivors. Methods: For this qualitative study, a focus group
      methodology, with a case study design, was used. The data were analyzed for
      themes using a social ecological conceptual framework. Results: Three focus
      groups were conducted with a total of 24 participants (N = 24). Participants
      defined quality of life as being able to engage in meaningful activities of daily
      living. Participants shared experiences of adapting to declining physical health
      and embracing new activities of daily living. They expressed hope and shared
      stories that demonstrated resiliency. Conclusion: The literature states that
      individuals aging with post-polio syndrome express concern that health providers
      often know little about their disability condition. The participants in this
      study reflected this experience by sharing feelings of misunderstanding from the
      medical community and expressing a desire to have more dynamic education for
      health providers.

PMID- 30202522
TI  - Roadbook for the implementation of next-generation sequencing in clinical
      practice in oncology and hemato-oncology in Belgium.
AB  - In the field of oncology research, next-generation sequencing has contributed
      significantly to the discovery of DNA mutations associated with diagnosis and
      prognosis. It also aids in the development of targeted therapies to specific
      mutations and the rise of personalized medicine. As part of molecular diagnostics
      in cancer patients, analysis by next-generation sequencing is becoming part of
      routine clinical practice. The introduction of this complex technology in a
      healthcare system comes with multiple challenges and requires a clear action
      plan. Such an action plan, as outlined in this paper, was developed in Belgium
      and includes steps in ensuring the quality and indications of NGS testing,
      installing data registration and tackling ethical issues. A final step is to
      perform a pilot study to control the access, quality, harmonization and expertise
      in DNA testing. This action plan can serve as a guide for similar initiatives by
      other countries to facilitate NGS implementation in clinical practice.

PMID- 30202525
TI  - Toads are plastic, it's fantastic! Or is it?

PMID- 30202524
TI  - Stroke prevalence among the Turkish population in a rural area of Istanbul: A
      community-based study.
AB  - Background: The population-based information on the prevalence of stroke from
      rural areas of Middle East countries including Turkey is unknown. Our aim is to
      evaluate the prevalence of stroke in those ?18 years in the Turkish population in
      a rural area of Istanbul. Methods: A cross-sectional door-to-door study was
      conducted in a rural area of Istanbul between 1 March and 30 March 2013. A
      research protocol recommended by World Health Organization for developing
      countries was used. Each screening teams consisted of one neurologist, one local
      nurse, and five surveyors. Teams were trained about the survey and questionnaire.
      The patients, who claimed to have suffered a stroke, were examined, and the
      diagnosis was confirmed by a neurologist on site. The findings and medical
      records were documented. Results: In total, 2906 people ?18 years were screened.
      50 stroke cases were detected. 80% of those were found to have had an ischemic
      stroke, 14% of those were hemorrhagic cases, and 6% of those had an unclassified
      stroke type. The overall prevalence rate in those ? 18 years was 1.7%. The
      male/female ratio was 0.92. Young (<45) stroke prevalence was found to be 0.6%.
      Conclusion: This study was the first of its kind to show the stroke prevalence
      among Turkish population ? 18 years in a rural area of Istanbul. When compared to
      other studies which investigate people ?45 years from Turkey, the result (in the
      same age group) was moderate high. The male/female ratio was low compared to many
      other studies.

PMID- 30202526
TI  - Surgical resection of extramedullary haematopoiesis in the posterior mediastinum.
AB  - Extramedullary haematopoiesis is a rare disease that is usually associated with
      haematologic disorders such as thalassemia, myelodysplastic syndrome, and
      hereditary spherocytosis. It frequently occurs in the liver, spleen, and lymph
      nodes. Rarely, it occurs in the posterior mediastinum. We report the case of a 59
      year-old man with lateral posterior mediastinal masses that were incidentally
      detected during treatment for hereditary spherocytosis. We performed video
      assisted thoracic surgery to confirm the diagnosis and differentiate the masses
      from neurogenic tumours and other posterior mediastinal diseases. The
      pathological findings were consistent with intrathoracic extramedullary
      haematopoiesis. Although extramedullary haematopoiesis can be managed without
      interventions, surgery may be required in some cases. In such cases, video
      assisted thoracoscopic surgery is advised because it is a useful and less
      invasive procedure.

PMID- 30202527
TI  - A three-decade review of telemetry studies on vultures and condors.
AB  - Telemetry-based movement research has become central for learning about the
      behavior, ecology and conservation of wide-ranging species. Particularly, early
      telemetry studies were conducted on vultures and condors due to three main
      reasons: i) these birds capture the curiosity of humans, ii) their large body
      size allows researchers to deploy large telemetry units, and iii) they are of
      high conservation concern. This has resulted in a great number of scientific
      articles that remain scattered throughout the literature. To achieve a more
      cohesive view of vultures and condors movement behavior, we review all telemetry
      studies published up to 2017. We first present a descriptive summary of the
      technical and design characteristics of these studies (e.g. target species,
      tagging location, number of individuals tagged) and go on to discuss them under a
      common conceptual framework; the Movement Ecology Paradigm. The articles found (N
      = 97) were mainly published in the last decade and based on the tagging of
      individuals from 14 species (61% of the extant species) and 24 countries.
      Foraging was the most in-depth investigated movement phase (25 studies), with
      studies covering several species, using both phenomenological and mechanistic
      approaches and tackling the role of different drivers of movement. In contrast,
      commuting and natal dispersal phases were only superficially investigated (3 and
      8 studies, respectively). Finally, studies dealing with the conservation and
      management also comprised a large portion of the reviewed articles (24 studies).
      Telemetry studies have revealed relevant details of vultures and condors
      movements, with highly accurate measurements of flight energetics and a better
      understanding of the morphological, physiological and context-dependent drivers
      that underlie the movement decisions of these birds. However, we also detected
      several information gaps. We expect this review helps researchers to focus their
      efforts and funds where more information is needed.

PMID- 30202528
TI  - Predictors and outcomes of early post-operative veno-arterial extracorporeal
      membrane oxygenation following infant cardiac surgery.
AB  - Background: We aimed to determine predictors of, and outcomes after, veno
      arterial extracorporeal membrane oxygenation instituted within 48 h after cardiac
      surgery (early ECMO) in young infants. Methods: Patients <= 6 weeks old having
      cardiac surgery from 2003 to 2012 were enrolled prospectively. Patients
      cannulated pre-operatively, intra-operatively, or >= 48 h post-operatively were
      excluded. Variables at p <= 0.1 on univariate regression were entered into
      multiple logistic regression to predict early ECMO. Early-ECMO cases were matched
      1:2 for six demographic variables, and death by age 2 years old (determined using
      conditional logistic regression; presented as odds ratio (OR), 95% confidence
      interval (CI)) and General Adaptive Composite scores at age 2 years (determined
      using Wilcoxon rank sum) were compared; p <= 0.05 was considered statistically
      significant. Results: Of 565 eligible patients over the 10-year period, 20 had
      early ECMO instituted at a mean (standard deviation) of 12.4 (11.4) h post
      operatively, 10 of whom had extracorporeal cardiopulmonary resuscitation. Of
      early-ECMO patients, 8 (40%) were found to have residual anatomic defects
      requiring intervention with catheterization (n = 1) and/or surgery (n = 7). On
      multiple regression, the post-operative day 1 highest vasoactive-inotrope score
      (OR 1.02; 95%CI 1.06,1.08; p < 0.001), highest lactate (OR 1.2; 95%CI 1.06,1.35;
      p = 0.003), and lowest base deficit (OR 0.82; 95%CI 0.71,0.94; p = 0.004), CPB
      time (OR 1.01; 95%CI 1.00,1.02; p = 0.002), and single-ventricle anatomy (OR
      5.35; 95%CI 1.66,17.31; p = 0.005) were associated with early ECMO. Outcomes at 2
      years old compared between early-ECMO and matched patients were mortality 11/20
      (55%) vs 11/40 (28%) (OR 3.22, 95%CI 0.98,10.63; p = 0.054) and General Adaptive
      Composite median 65 [interquartile range (IQR) 58, 81.5] in 9 survivors vs 93
      [IQR 86.5, 102.5] in 29 survivors (p = 0.02). Conclusions: The identified risk
      factors for, and outcomes after, having early ECMO may aid decision making in the
      acute period and confirm that neurodevelopmental follow-up for these children is
      necessary. The hypothesis that earlier institution of ECMO may improve long-term
      outcomes requires further study.

PMID- 30202529
TI  - Treatment of patients with sepsis in a closed intensive care unit is associated
      with improved survival: a nationwide observational study in Japan.
AB  - Background: The aim of this study is to investigate the association between
      treatment in a closed ICU and survival at discharge in patients with sepsis.
      Methods: This is a post hoc analysis utilizing data from the Japan Septic
      Disseminated Intravascular Coagulation study, including data from patients with
      sepsis from 2011 to 2013. Multiple logistic regression analysis was used to
      estimate the association between ICU policy and survival at discharge, and
      propensity score matching analysis was performed including the same covariates as
      a sensitivity analysis. Multiple linear regression analysis for the length of ICU
      stay in surviving patients was also performed with adjustments for the same
      covariates. Results: Two thousand four hundred ninety-five patients were
      analyzed. The median Acute Physiology and Chronic Health Evaluation (APACHE) II
      score was 22 [17-29], the median Sequential Organ Failure Assessment (SOFA) score
      was 9 [7-12], and the overall mortality was 33%. There were 979 patients treated
      in 17 open ICUs and 1516 patients in 18 closed ICUs. In comparison, the APACHE II
      score and SOFA scores were significantly higher in patients in closed ICUs
      (closed vs open = 23 [18-29] vs 21 [16-28]; p < .001, 9 [7-13] vs 9 [6-12]; p =
      0.004). There was no difference in the unadjusted mortality (closed vs open;
      33.1% vs 33.2%), but in multiple logistic regression analysis, treatment in a
      closed ICU is significantly associated with survival at discharge (odds ratio =
      1.59, 95% CI [1.276-1.827], p = .001). The sensitivity analysis (702 pairs of the
      matching) showed a significantly higher survival rate in the closed ICU (71.8% vs
      65.2%, p = 0.011). The length of ICU stay of patients in closed ICUs was
      significantly shorter (20% less). Conclusion: This Japanese nationwide analysis
      of patients with sepsis shows a significant association between treatment in a
      closed ICU and survival at discharge, and a 20% decrease in ICU stay.

PMID- 30202531
TI  - Albumin, copper, manganese and cobalt levels in children suffering from sickle
      cell anemia at Kasumbalesa, in Democratic Republic of Congo.
AB  - Background: Sickle Cell Anemia (SCA) is characterized by high levels of oxidative
      stress markers and low levels of antioxidant capacity. Antioxidant defence
      mechanisms against the harmful effects of ROS requires cellular and extracellular
      enzymes. These enzymes requires micronutrient for complete activity. Information
      on micronutrients such as manganese, cobalt and copper in SCA population was
      poorly documented in the literature. Methods: Plasma copper, manganese, cobalt
      and albumin concentrations determined by atomic absorption spectrophotometry were
      compared between two groups of children: 76 with SCA (Hb-SS) and 76 without SCA
      (controls). This study was conducted in the Muhona Hospital of Kasumbalesa, which
      is situated in a rural and low in resources. Results: The mean age was 10.0 years
      (SD = 5.4) in SCA children and 9.2 years (SD = 4.7) in the control group. The
      levels of cobalt, manganese, copper and albumin were not different between the
      two groups (p > 0.05). Conclusion: In our study, albumin, manganese, cobalt and
      copper values did not differ between SCA children in steady state and Hb-AA
      children. The lack of differences in plasma elemental concentrations between the
      two groups in context of increased demands in the SCA group, may represent
      adequate compensatory intake or elemental dyshomeostasis in the SCA group.

PMID- 30202530
TI  - "Low-" versus "high"-frequency oscillation and right ventricular function in
      ARDS. A randomized crossover study.
AB  - Background: Recent, large trials of high-frequency oscillation (HFO) versus
      conventional ventilation (CV) in acute respiratory distress syndrome (ARDS)
      reported negative results. This could be explained by an HFO-induced right
      ventricular (RV) dysfunction/failure due to high intrathoracic pressures and
      hypercapnia. We hypothesized that HFO strategies aimed at averting/attenuating
      hypercapnia, such as "low-frequency" (i.e., 4 Hz) HFO and 4-Hz HFO with tracheal
      gas insufflation (HFO-TGI), may result in an improved RV function relative to
      "high-frequency" (i.e., 7 Hz) HFO (which may promote hypercapnia) and similar RV
      function relative to lung protective CV. Methods: We studied 17 patients with
      moderate-to-severe ARDS [PaO2-to-inspiratory O2 fraction ratio (PaO2/FiO2) <
      150]. RV function was assessed by transesophageal echocardiography (TEE).
      Patients received 60 min of CV for TEE-guided, positive end-expiratory pressure
      (PEEP) "optimization" and subsequent stabilization; 60 min of 4-Hz HFO for "study
      mean airway pressure (mPaw)" titration to peripheral oxygen saturation >= 95%,
      without worsening RV function as assessed by TEE; 60 min of each tested HFO
      strategy in random order; and another 60 min of CV using the pre-HFO, TEE-guided
      PEEP setting. Study measurements (i.e., gas exchange, hemodynamics, and TEE data)
      were obtained over the last 10 min of pre-HFO CV, of each one of the three tested
      HFO strategies, and of post-HFO CV. Results: The mean "study HFO mPaw" was 8-10
      cmH2O higher relative to pre-HFO CV. Seven-Hz HFO versus 4-Hz HFO and 4-Hz HFO
      TGI resulted in higher mean +/- SD right-to-left ventricular end-diastolic area
      ratio (RVEDA/LVEDA) (0.64 +/- 0.15 versus 0.56 +/- 0.14 and 0.52 +/- 0.10,
      respectively, both p < 0.05). Higher diastolic/systolic eccentricity indexes
      (1.33 +/- 0.19/1.42 +/- 0.17 versus 1.21 +/- 0.10/1.26 +/- 0.10 and 1.17 +/-
      0.11/1.17 +/- 0.13, respectively, all p < 0.05). Seven-Hz HFO resulted in 18-28%
      higher PaCO2 relative to all other ventilatory strategies (all p < 0.05). Four-Hz
      HFO-TGI versus pre-HFO CV resulted in 15% lower RVEDA/LVEDA, and 7%/10% lower
      diastolic/systolic eccentricity indexes (all p < 0.05). Mean PaO2/FiO2 improved
      by 77-80% during HFO strategies versus CV (all p < 0.05). Mean cardiac index
      varied by <= 10% among strategies. Percent changes in PaCO2 among strategies were
      predictive of concurrent percent changes in measures of RV function (R2 = 0.21
      0.43). Conclusions: In moderate-to-severe ARDS, "short-term" 4-Hz HFO strategies
      resulted in better RV function versus 7-Hz HFO, partly attributable to improved
      PaCO2 control, and similar or improved RV function versus CV. Trial registration:
      This study was registered 40 days prior to the enrollment of the first patient at
      ClinicalTrials.gov, ID no. NCT02027129, Principal Investigator Spyros D.
      Mentzelopoulos, date of registration January 3, 2014.

PMID- 30202532
TI  - Relationship between simultaneous exposure to ergonomic risk factors and work
      related lower back pain: a cross-sectional study based on the fourth Korean
      working conditions survey.
AB  - Background: It is well known that ergonomic risk factors and back pain are
      related. However, few studies have examined the relationship between simultaneous
      exposure to these risk factors and back pain in a Korean population. We aimed to
      investigate the relationship between simultaneous exposure to ergonomic risk
      factors and work-related lower back pain (LBP) based on the fourth Korean Working
      Conditions Survey (KWCS). Method: The fourth KWCS (2014) was used for this study.
      Chi-square tests and logistic regression were used to assess relationship between
      5 ergonomic risk factors and work-related LBP. We also analyzed the relationship
      between simultaneous exposure to 2 risk factors and work-related LBP. Results:
      All 5 ergonomic risk factors (fatigue-inducing and painful posture; lifting or
      moving people; dragging, pushing, or moving heavy objects; standing posture; and
      repetitive hand or arm movements) were significantly correlated with work-related
      LBP in the severe exposure group (adjusted odd ratios [aOR] 5.09, 95% confidence
      interval [CI] 4.46-5.83; aOR 1.98, 95% CI 1.62-2.42; aOR 2.09, 95% CI 1.82-2.40;
      aOR 1.79, 95% CI 1.60-2.01; aOR 2.04, 95% CI 1.82-2.30, respectively). When
      exposed to 2 risk factors simultaneously, the relationship between exposure and
      work-related LBP was not greater than exposure to only 1 risk factor in our study
      (usually exposed to 'fatigue-inducing or painful posture' aOR 2.17, 95% CI 2.02
      2.34; high exposure to both 'fatigue-inducing or painful posture' and 'dragging,
      pushing, or moving heavy objects' aOR 2.00, 95% CI 1.82-2.20). Conclusions: There
      was a strong relationship between severe exposure to each ergonomic risk factor
      and work-related LBP. However, when exposed to 2 ergonomic risk factors
      simultaneously, the relationship between exposure and work-related LBP was not
      stronger than when exposed to only 1 risk factor in our study.

PMID- 30202534
TI  - Use of intravenous immunoglobulin for the treatment of autoimmune encephalitis:
      audit of the NHS experience.
AB  - Objectives: The treatments of limbic and other autoimmune encephalitis include
      immunosuppression, symptomatic treatment, and in the case of paraneoplastic
      syndromes, appropriate therapy for underlying neoplasms. When immunotherapy is
      considered, intravenous immunoglobulin is one option for treatment, either alone
      or in combination with corticosteroids. To date, however, evidence for the use of
      intravenous immunoglobulin in this context comes from case series/expert reviews
      as no controlled trials have been performed. We aimed to analyse the NHS England
      Database of intravenous immunoglobulin usage, which was designed to log use and
      guide procurement, to explore usage and therapeutic effect of intravenous
      immunoglobulin in autoimmune encephalitis in England. Design: We conducted a
      retrospective audit and review of the NHS England Database on intravenous
      immunoglobulin use. Setting: NHS England Database of intravenous immunoglobulin
      use which covers secondary and tertiary care prescribing and use of intravenous
      immunoglobulin for all patients in hospitals in England. Participants: Hospital
      in-patients with confirmed or suspected autoimmune/limbic encephalitis between
      September 2010 and January 2017. Results: A total of 625 patients who were 18
      years of age or older were treated with intravenous immunoglobulin for autoimmune
      encephalitis, of whom 398 were determined as having 'highly likely' or 'definite'
      autoimmune/limbic encephalitis. Ninety-six percent were treated with a single
      course of intravenous immunoglobulin. The availability and accuracy of reporting
      of outcomes was very poor, with complete data only available in 27% of all cases.
      Conclusions: This is the first review of data from this unique national database.
      Whilst there was evidence for clinical improvement in many cases of patients
      treated with intravenous immunoglobulin, the quality of outcome data was
      generally inadequate. Methods to improve quality, accuracy and completeness of
      reporting are crucial to maximise the potential value of this resource as an
      auditing tool.

PMID- 30202533
TI  - Knowledge, attitude, perception and practice regarding antimicrobial use in upper
      respiratory tract infections in Qatar: a systematic review.
AB  - Objective: To explore the knowledge, attitude, perception and practice towards
      antimicrobial use in upper respiratory tract infections in patients visiting
      healthcare settings in Qatar. Design: Systematic review was performed using a
      predetermined protocol and in accordance with standardized reporting guidelines.
      MEDLINE, PubMed, EMBASE, Global Health and PsycINFO were searched for relevant
      published studies using relevant MESH terms and keywords. Setting: All healthcare
      settings in Qatar including both inpatient and ambulatory care. Participants: All
      published articles exploring the antimicrobial use in upper respiratory tract
      infections at any health setting in Qatar were considered for inclusion in the
      study. No age, gender or population were excluded. Main Outcome Measures: The
      outcome of interest was antimicrobial use in upper respiratory tract infections
      in Qatar. We included all related studies to explore the knowledge, attitude,
      perception and practice for patients visiting all health care settings. Results:
      Three articles were included, one in a primary care setting, one in a secondary
      care setting and one in the private sector. Overprescribing was noted in all
      settings. Our findings demonstrate low expectations to receive antibiotics, among
      the Qatari population, in primary care (28.1%). In fact, the majority of patients
      would be satisfied with reassurance rather than receiving antimicrobials. Many
      patients were satisfied with explanation from physicians and counselling. Private
      sector registered high prevalence of antimicrobial misuse for respiratory tract
      infections in which 85% deemed inappropriate. This finding was also noted at a
      medical intensive care unit which showed high antimicrobial use (76%) and
      respiratory tract infections accounted for 57% of prescriptions. Conclusion:
      Studies are needed to determine factors and population-based rates of
      antimicrobial use in all healthcare settings. There is also a need for
      interventional programs for both physicians and public on appropriate use of
      antimicrobials to combat global antimicrobial resistance.

PMID- 30202535
TI  - Mental health capacity building in refugee primary health care settings in Sub
      Saharan Africa: impact, challenges and gaps.
AB  - Background: In 2015, the United Nations High Commissioner for Refugees started a
      process of mental health capacity building in refugee primary health care
      settings in seven countries in Sub-Saharan Africa, ultimately aiming to decrease
      the treatment gap of mental, neurological and substance use (MNS) conditions in
      these operations. In 2015 and 2016, a specialized non-governmental organization,
      the War Trauma Foundation, trained 619 staff with the mental health gap action
      programme (mhGAP) Humanitarian Intervention Guide (HIG), a tool designed to guide
      clinical decision making in humanitarian settings. Methods: This paper describes
      the results of a process evaluation of a real-life implementation project by an
      external consultant, one and a half years after starting the programme. Results:
      The mhGAP-HIG capacity building efforts had various effects contributing to the
      integration of mental health in refugee primary health care. Facility-and
      community-based staff reported strengthened capacities to deliver mental health
      and psychosocial support interventions as well as changes in their attitude
      towards people suffering from MNS conditions. Service delivery and collaboration
      amongst different intervention levels improved. The scarcity of specialized staff
      in these settings was a major barrier, hindering the setting-up of supervision
      mechanisms. Conclusion: Mental health training of non-specialized staff in
      complex humanitarian settings is feasible and can lead to increased competency of
      providers. However, capacity building is a 'process' and not an 'event' and mhGAP
      trainings are only one element in a spectrum of activities aimed at integrating
      mental health into general health care. Regular supervision and continuing on-the
      job training are in fact critical to ensure sustainability.

PMID- 30202536
TI  - Prevalence and correlates of unintended pregnancy in Ghana: Analysis of 2014
      Ghana Demographic and Health Survey.
AB  - Background: Unintended pregnancies increase levels of stress, adoption of risky
      behaviours and impact on women's general quality of life. In Ghana, in spite of
      the paucity of literature on unintended pregnancies, the phenomenon is high
      especially among women in the early years of their reproductive health. This
      study therefore sought to investigate the prevalence and correlates of unintended
      pregnancies in Ghana. Methods: This study made use of data from the 2014 Ghana
      Demographic and Health Survey. Descriptive statistics were conducted whereby
      prevalence of unintended pregnancy was presented in proportions. This was
      followed by binary logistic regression to investigate correlates associated with
      unintended pregnancy. Results: Descriptively, unintended pregnancies were high
      among women aged 15-19 years (69.4%), unmarried women (45.1%) and non-working
      women (40.0%). Factors found to be associated with the phenomenon were age,
      parity and level of education. The binary logistic regression revealed that women
      in middle wealth category were 1.42 times more probable of having unintended
      pregnancy than poor women whilst rich women were less likely to experience
      unintended pregnancy [OR = 0.89, CI = 0.35-0.79] as compared to poor women.
      Again, urban women were more likely to experience unintended pregnancies as
      compared rural women [OR = 1.39, CI = 0.86-1.95]. Conclusion: The study has
      indicated that specific interventions must be targeted at different categories of
      women. The Reproductive and Child Health unit of the Ghana Health Service ought
      to collaborate with non-governmental organisations to intensify access to well
      tailored family planning services among adolescents and young women, women out of
      marriage and the non-working category.

PMID- 30202537
TI  - The Hoffman report, the Central Intelligence Agency, and the defense of the
      nation: A personal view.
AB  - I was asked by the Central Intelligence Agency in the spring of 2002 about how
      the research on learned helplessness could help captured Americans resist and
      evade torture and interrogation. There was no discussion of how learned
      helplessness could be used with detainees nor any mention of the interrogation of
      detainees. James Mitchell and Bruce Jessen later created a program of "enhanced
      interrogation" of detainees and it was incorrectly reported that they based it on
      the theory of learned helplessness. I played no role at all in these
      developments, and I am grieved that scientific research created to relieve
      helplessness and depression might have been used for brutal interrogations. The
      unfounded attacks on me and others, however, may have been intended to discourage
      young psychologists from working with the Department of Defense, and I urge
      American Psychological Association not to waver in its long-standing commitment
      to serve the nation.

PMID- 30202538
TI  - The American Psychological Association's Hoffman report allegations of my
      association with the "CIA torture" program.
AB  - Until now, I have not responded to the undocumented and untrue portrayal of me in
      the Hoffman report, or the newspaper and email accounts of my alleged role in
      "torture." I have waited several years because I believed that the American
      Psychological Association leadership would completely disavow the Hoffman report
      and find a way to restore my reputation as well as that of the other former
      American Psychological Association presidents and the small number of its senior
      staff who were also falsely accused. Although this has not yet happened, I remain
      optimistic that it will. Here I present the facts as they relate to me.

PMID- 30202539
TI  - Barriers and facilitators to adhering to an anti-inflammatory diet for
      individuals with spinal cord injuries.
AB  - The purpose of this study was to explore the barriers and facilitators of an anti
      inflammatory diet in people with spinal cord injury. Six participants (age range
      of 23-68 years, three women and three men) who had previously completed an anti
      inflammatory diet study were interviewed. Facilitators identified were family
      support, autonomy over meal choice, peer support, health benefits gained, and
      implementation of adherence strategies. The main barriers discussed were lack of
      motivation after study period ended, social events, diet expenses, and lack of
      knowledge about the diet. Several health benefits including reductions in pain,
      edema, and improvements in cognition and mobility were reported.

PMID- 30202542
TI  - Erratum: Bilateral patellar fractures and increased cortical bone thickness
      associated with long-term oral alendronate treatment in a cat.
AB  - [This corrects the article DOI: 10.1177/2055116917727137.].

PMID- 30202541
TI  - Failure to detect Tritrichomonas foetus in a cross-sectional survey in the
      populations of feral cats and owned outpatient cats on St Kitts, West Indies.
AB  - Objectives: For over two decades, feline trichomonosis caused by Tritrichomonas
      foetus has been recognized as a large-bowel protozoan disease of the domestic
      cat. It has a wide distribution, but no reports exist in the Caribbean. The
      objectives of this study were to detect the presence of T foetus and its
      prevalence in the domestic cat on St Kitts, West Indies. Methods: A cross
      sectional study was performed between September 2014 and December 2015. This
      study recruited 115 feral cats from a trap-neuter-return program and 37 owned
      cats treated as outpatients at the university veterinary clinic. Fresh feces were
      inoculated in InPouch culture medium, as per the manufacturer's instructions. In
      addition, PCR was performed using primers for T foetus. DNA extraction with
      amplification using primers of a Feliscatus NADH dehydrogenase subunit 6 was used
      as a housekeeping gene for quality control. Results: Only two owned cats had
      reported diarrhea in the preceding 6 months. None of the 152 samples were
      positive on InPouch culture microscopic examination. Only 35/69 feral cat fecal
      DNA samples were positive for the housekeeping gene, of which none tested PCR
      positive for T foetus. Conclusions and relevance: T foetus was not detected by
      culture and PCR in feral cats and owned cats on St Kitts. A high proportion of
      PCR inhibitors in the DNA samples using a commercial fecal DNA kit can lead to
      underestimating the prevalence, which should be taken into consideration when a
      survey on gastrointestinal pathogens depends exclusively on molecular detection.

PMID- 30202540
TI  - Epidemiology and clinical outcomes of feline immunodeficiency virus and feline
      leukaemia virus in client-owned cats in New Zealand.
AB  - Objectives: The objectives were to collect baseline data on the occurrence,
      testing and vaccination practices, and clinical outcomes of feline leukaemia
      virus (FeLV) and feline immunodeficiency virus (FIV) in New Zealand. Methods: A
      cross-sectional survey of 423 veterinary practices in New Zealand was performed
      to collect data on FeLV and FIV testing and vaccination during the 2015 calendar
      year. Clinical records from 572 cats tested using a point-of-care ELISA at a
      first-opinion veterinary practice between 7 April 2010 and 23 June 2016 were also
      obtained and multivariable logistic regression models were constructed to
      identify risk factors for test positivity. Survival times were estimated using
      Kaplan-Meier methods. Results: The survey was completed by 112 clinics (26.4%) of
      which 72 performed in-house testing. Of the 2125 tests performed, 56 (2.6%) were
      positive for FeLV and 393 (18.5%) were positive for FIV. Fewer than 1% of cats
      were vaccinated for FeLV, with veterinarians citing low perceived prevalence as
      the primary reason for not vaccinating. Being male compared with being female and
      having clinical evidence of immunosuppression were significant risk factors for
      both FeLV and FIV test positivity. The median survival times of FeLV and FIV test
      positive cats were 10 days (95% confidence interval [CI] 0-16) and 650 days (95%
      CI 431-993), respectively. Conclusions and relevance: Testing and vaccination for
      FeLV and FIV in New Zealand appears targeted towards high-risk animals, which may
      bias prevalence estimates. Baseline data should be monitored for changes in FeLV
      epidemiology now commercial vaccines are no longer available.

PMID- 30202543
TI  - Caudal mandibular fracture repair using three-dimensional printing, presurgical
      plate contouring and a preformed template to aid anatomical fracture reduction.
AB  - Case summary: Two cats were presented with mandibular fractures following head
      trauma. Following a CT scan, both were diagnosed with fractures of the ramus. The
      CT scans were used to print three-dimensional (3D) models of the mandibular
      fractures, which were used to pre-contour stainless steel mini-plates. These were
      fixed to the models and the screw positions used to produce a stainless steel
      template. The template was used as a pattern during surgery to drill holes in the
      ramus so that the pre-contoured mini-plates could be fixed in the exact same
      position as they had been on the 3D model. The fractures healed in both cats
      achieving normal jaw function and occlusion. Relevance and novel information:
      Conventional techniques used to treat caudal mandibular fractures in cats, such
      as maxillomandibular fixation and bignathic encircling and retaining device
      (BEARD), are associated with significant patient morbidity and postoperative
      complications. Internal rigid fixation is difficult because of small bone size,
      requirement for considerable plate contouring and difficulty in achieving
      accurate anatomical reduction of caudal mandibular fractures. These are the first
      reported cases of mini-plate fixation of caudal mandibular fractures in cats
      using 3D models, pre-contouring of bone plates and the use of a template to
      facilitate accurate plate positioning, which may provide an alternative technique
      suitable for fixing caudal mandibular fractures in cats.

PMID- 30202544
TI  - Tracking feels oppressive and 'punishy': Exploring the costs and benefits of self
      monitoring for health and wellness.
AB  - Self-monitoring is the cornerstone of many health and wellness persuasive
      interventions. However, applications designed to promote health and wellness that
      use this strategy have recorded varying degrees of success. In this study, we
      investigated why the self-monitoring strategy might work in some contexts and
      fail in others. We conducted a series of large-scale studies, with a total of
      1768 participants, to explore the strengths and weaknesses of the self-monitoring
      strategy. Our results uncover important strengths and weaknesses that could
      facilitate or hinder the effectiveness of self-monitoring to promote the health
      and wellness of its users. The strengths include its tendency to reveal problem
      behaviours, provide real and concrete information, foster reflection, make people
      accept responsibility, create awareness and raise users' consciousness about
      their health and wellness. Some of the weaknesses include its tendency to provoke
      health disorder, be tedious and boring. We contribute to the digital health
      community by offering design guidelines for operationalising self-monitoring to
      overcome its weaknesses and amplify its strengths.

PMID- 30202545
TI  - State of emergency contraception in the U.S., 2018.
AB  - Emergency contraception is indicated in instances of unprotected sexual
      intercourse, including reproductive coercion, sexual assault, and contraceptive
      failure. It plays a role in averting unintended pregnancies due to inconsistent
      use or non-use of contraception. Options for emergency contraception vary by
      efficacy as well as accessibility within the U.S. This paper provides an overview
      of levonorgestrel (Plan B One-Step and generic counterparts), ulipristal acetate
      (sold as ella), and the copper intrauterine device (IUD, sold as ParaGard),
      including the mechanisms of action, administration, efficacy, drug interactions,
      safety, side effects, advantages, and drawbacks. It will also review current
      misconceptions about emergency contraception and access for subpopulations,
      including adolescents, immigrants, survivors of sexual assault, rural
      populations, and military/veteran women. This paper will address barriers such as
      gaps in knowledge, and financial, health systems, and practice barriers.
      Continuing areas of research, including the impact of body weight on the efficacy
      of emergency contraceptive pills and potential interactions between ulipristal
      acetate and ongoing hormonal contraceptives, are also addressed.

PMID- 30202547
TI  - Will eye tracking change the way we diagnose and classify concussion and
      structural brain injury?

PMID- 30202546
TI  - Concussion in the National Hockey League: a systematic review of the literature.
AB  - Players in the National Hockey League (NHL) are often sidelined by injuries,
      including concussion. The acute, intermediate and long-term effects of repetitive
      head trauma remain a concern of many. In 1997, the NHL and NHL Players
      Association established the NHL-NHL Players Association Concussion Program to
      diagnose, assess and treat concussion via a standardized and scientific approach.
      Documenting and analyzing the trends, incidence and underlying mechanisms of
      concussion may help in devising future prevention and treatment plans for
      concussion in hockey in general and the NHL in particular. The purpose of this
      study, therefore, was to systematically review and summarize the existing
      published literature on the trends, incidence rates and underlying mechanisms of
      concussion in the NHL.

PMID- 30202548
TI  - Sensitivity and specificity of an eye movement tracking-based biomarker for
      concussion.
AB  - Object: The purpose of the current study is to determine the sensitivity and
      specificity of an eye tracking method as a classifier for identifying concussion.
      Methods: Brain injured and control subjects prospectively underwent both eye
      tracking and Sport Concussion Assessment Tool 3. The results of eye tracking
      biomarker based classifier models were then validated against a dataset of
      individuals not used in building a model. The area under the curve (AUC) of
      receiver operating characteristics was examined. Results: An optimal classifier
      based on best subset had an AUC of 0.878, and a cross-validated AUC of 0.852 in
      CT- subjects and an AUC of 0.831 in a validation dataset. The optimal
      misclassification rate in an external dataset (n = 254) was 13%. Conclusion: If
      one defines concussion based on history, examination, radiographic and Sport
      Concussion Assessment Tool 3 criteria, it is possible to generate an eye tracking
      based biomarker that enables detection of concussion with reasonably high
      sensitivity and specificity.

PMID- 30202549
TI  - Returning the student to school after concussion: what do clinicians need to
      know?
AB  - Participation in school is vital to a child's academic and social development.
      Following concussion, returning the student to school can pose several challenges
      for families, healthcare providers and school personnel. The complex
      constellation of postconcussion symptoms can impair learning and can make the
      school environment intolerable. Research evidence to guide the return to school
      process is lacking, but protocols have been proposed that outline a gradual
      reintroduction to school with academic accommodations tailored to the student's
      specific symptoms. Key medical and school personnel must understand their
      respective roles to optimize the process. This review of the current literature
      examines the available data and expert recommendations that can support a
      student's successful return to school following concussion.

PMID- 30202551
TI  - Concussion: an Introduction.

PMID- 30202550
TI  - Variability of the modified Balance Error Scoring System at baseline using
      objective and subjective balance measures.
AB  - Aim: To investigate preseason modified Balance Error Scoring System (mBESS)
      performance in a collegiate football cohort; to compare scores to an objective
      mobile balance measurement tool. Materials & methods: Eighty-two athletes
      completed simultaneous balance testing using mBESS and the King-Devick Balance
      Test, an objective balance measurement tool. Errors on mBESS and objective
      measurements in the double-leg, single-leg (SS) and tandem stances were compared.
      Results: Mean mBESS error score was 7.23 +/- 4.65. The SS accounted for 74% of
      errors and 21% of athletes demonstrated the maximum error score. There was no
      significant correlation between mBESS score and objective balance score.
      Conclusion: The high variability and large number of errors in the SS raises
      concerns over the utility of the SS in identifying suspected concussion.

PMID- 30202554
TI  - Concussion research at the National Institutes of Health: an update from the
      National Institute of Neurological Disorders and Stroke.

PMID- 30202552
TI  - The King-Devick test of rapid number naming for concussion detection: meta
      analysis and systematic review of the literature.
AB  - Background: Vision encompasses a large component of the brain's pathways, yet is
      not represented in current sideline testing. Objectives: We performed a meta
      analysis of published data for a vision-based test of rapid number naming (King
      Devick [K-D] test). Studies & methods: Pooled and meta-analysis of 15 studies
      estimated preseason baseline K-D scores and sensitivity/specificity for
      identifying concussed versus nonconcussed control athletes. Result: Baseline K-D
      (n = 1419) showed a weighted estimate of 43.8 s (95% CI: 40.2, 47.5; I2 = 0.0%;
      p=0.85 - indicating very little heterogeneity). Sensitivity was 86% (96/112
      concussed athletes had K-D worsening; 95% CI: 78%, 92%); specificity was 90%
      (181/202 controls had no worsening; 95% CI: 85%, 93%). Conclusion: Rapid number
      naming adds to sideline assessment and contributes a critical dimension of vision
      to sports-related concussion testing.

PMID- 30202553
TI  - Neuroenergetics of traumatic brain injury.
AB  - A subset of traumatic brain injury (TBI) patients exhibit cognitive deficits
      later in life which may be due to the underlying pathology associated with
      Alzheimer's disease (AD) or chronic traumatic encephalopathy. The similarities
      between chronic traumatic encephalopathy and AD merit investigation of
      potentially similar mechanisms underlying the two diseases. Experimental and
      clinical studies of AD brains have revealed that insulin resistance links
      metabolic dysfunction to the neurodegeneration and cognitive deficits associated
      with AD. Recent work in experimental TBI has established that recovery is
      dependent on the return of normal brain metabolism and mounting evidence for a
      role of brain insulin in regulating central metabolism suggests that TBI, like
      AD, results in central insulin resistance. Here, we review the converging
      evidence from AD, TBI and diabetes research linking insulin insensitivity to
      neurodegeneration.

PMID- 30202555
TI  - Update on fluid biomarkers for concussion.
AB  - Concussions are difficult to diagnose and symptoms may not appear immediately. As
      an accurate initial diagnosis has profound implications for the clinical
      management, there is an unmet need for better diagnostic tools. Fluid biomarkers
      for CNS injury may represent such tools. These markers are often proteins,
      peptides or other molecules with selective or high expression in the brain, which
      can be measured in the cerebrospinal fluid or blood as they leak out or get
      secreted into the biofluid in response to the injury. Here, we review the
      literature on fluid markers of neuronal, axonal and astroglial injury and
      response mechanisms to diagnose CNS injury upon head impact and to determine when
      the injurious process has resolved.

PMID- 30202557
TI  - Sleep disturbance in patients with chronic concussive effects.
AB  - Aim: Sleep disturbance is relatively overlooked in concussion treatment although
      sleep disorders may prolong or exacerbate symptoms after a concussion. We looked
      at the incidence of both sleep disturbance and postconcussion symptoms in a
      sample of recently concussed individuals. Methods & results: We evaluated scores
      on the insomnia severity index (ISI) and postconcussion symptom scale (PCSS) in
      96 participants with persistent symptoms. Sleep disturbance significantly
      contributed to the severity of postconcussive symptoms and length of recovery;
      this effect was less pronounced in athletes. Conclusion: These results suggest a
      relationship between sleep problems and the time course of recovery from
      concussive injury. Clinicians who regularly treat concussion would benefit from a
      more thorough consideration of sleep function in the assessment of postconcussive
      symptoms.

PMID- 30202558
TI  - Concussion knowledge among amateur motocross riders.
AB  - Aim: There has been considerable increase in concussion awareness and risks;
      however, extreme sports such as motocross have received scant attention. The
      purpose of this study was to assess concussion knowledge among motocross riders
      and determine differences based on demographic factors. Methodology & results:
      782 motocross riders responded to an Internet-based questionnaire, and
      participant's knowledge score was 14.3 +/- 2.7 out of 20 and symptom recognition
      was 6.8 +/- 1.4 out of 8. Riders who had performed baseline concussion testing or
      received formal concussion education demonstrated higher knowledge scores.
      Rider's demographics did not predict outcome measures. Conclusions: Considerable
      misconceptions and lack of symptom knowledge persist among motocross riders and
      these results can be used for future interventions to improve concussion
      reporting.

PMID- 30202556
TI  - Prolonged cognitive-motor impairments in children and adolescents with a history
      of concussion.
AB  - Aim: We investigated whether children and adolescents with concussion history
      show cognitive-motor integration (CMI) deficits. Method: Asymptomatic children
      and adolescents with concussion history (n = 50; mean 12.84 years) and no history
      (n = 49; mean: 11.63 years) slid a cursor to targets using their finger on a dual
      touch-screen laptop; target location and motor action were not aligned in the CMI
      task. Results: Children and adolescents with concussion history showed prolonged
      CMI deficits, in that their performance did not match that of no history controls
      until nearly 2 years postevent. Conclusion: These CMI deficits may be due to
      disruptions in fronto-parietal networks, contributing to an increased
      vulnerability to further injury. Current return-to-play assessments that do not
      test CMI may not fully capture functional abilities postconcussion.

PMID- 30202559
TI  - The effect of concussion history on cognitive-motor integration in elite hockey
      players.
AB  - Aim: To observe the effects of concussion history on cognitive-motor integration
      in elite-level athletes. Methods: The study included 102 National Hockey League
      draft prospects (n = 51 concussion history [CH]; n = 51 no history [NC]).
      Participants completed two computer-based visuomotor tasks, one involved
      'standard' visuomotor mapping and one involved 'nonstandard' mapping in which
      vision and action were decoupled. Results: We observed a significant effect of
      group on reaction time (CH slower) and accuracy (CH worse), but a group by
      condition interaction only for reaction time (p < 0.05). There were no other
      deficits found. We discussed these findings in comparison to our previous work
      with non-elite athletes. Conclusion: Previously concussed elite-level athletes
      may have lingering neurological deficits that are not detected using standard
      clinical assessments.

PMID- 30202560
TI  - The partner's experience of traumatic brain injury and its recovery.

PMID- 30202562
TI  - The financial toll of career-ending concussions in professional hockey.
AB  - Aim: Several high-profile professional hockey players have retired due to career
      ending concussions sustained in the National Hockey League (NHL). We sought to
      determine the salary cost of career-ending concussions in the NHL. Methods:
      Concussion-induced retirements from 1995 to 2015 were identified using public
      media sources. The number of missed games due to a player's final concussion was
      multiplied by per game salary to determine cost. Results: In total, 35 players
      were identified: the total cost to teams and insurers of career-ending
      concussions was US$135,476,777. Half of the total consisted of salaries owing
      three players with contracts still active in 2015. Conclusion: The financial
      impact of concussion-induced retirements provides another reason for professional
      leagues to take measures to better protect their players from concussion.

PMID- 30202561
TI  - Subconcussive impacts and imaging findings over a season of contact sports.
AB  - The effect of repeated subconcussive head impacts in youth and high school sports
      on the developing brain is poorly understood. Emerging neuroimaging data
      correlated with biomechanical exposure metrics are beginning to demonstrate
      relationships across a variety of modalities. The long-term consequences of these
      changes are unknown. A review of the currently available literature on the effect
      of subconcussive head impacts on youth and high school-age male football players
      provides compelling evidence for more focused studies of these effects in these
      vulnerable populations.

PMID- 30202564
TI  - New technology and potential for telemedicine in battlefield brain injury
      diagnostics.

PMID- 30202563
TI  - Identification of hidden health utilization services and costs in adults awaiting
      tertiary care following mild traumatic brain injury in Toronto, Ontario, Canada.
AB  - Aim: The cognitive, emotional, behavioral and physical impairments experienced by
      adults after mild traumatic brain injury (mTBI) can produce substantial
      disability, with 15-20% requiring referral to tertiary care (TC) for persistent
      symptoms. Methods: A convenience sample of 201 adult patients referred to TC as a
      result of mTBI was studied. Self-reported data were collected at first TC visit,
      on average 10 months postinjury. Patients reported the type and intensity of
      healthcare provider visit(s) undertaken while awaiting TC. Results: On average
      males reported 37 and females 30 healthcare provider visits, resulting in over
      $500,000 Canadian dollars spent on potentially excess mTBI care over 1 year.
      Discussion: Based on conservative estimate of 15% of mTBI patients receiving TC,
      this finding identifies a possible excess in care of $110 million for Ontario.
      Accurate diagnosis of mTBI and early coordination of follow-up care for those
      needing TC could increase cost-effectiveness.

PMID- 30202565
TI  - Summary of the 2015 University of Michigan Sport Concussion Summit.
AB  - Discussions surrounding concussion have made their way into the public sphere
      over the previous decade with media attention and coverage of the injury fueling
      public debate. These conversations have devolved into discussions on banning
      contact and collision sports and raised legal questions surrounding injury
      management. Questions raised about concussion eclipse what science can answer,
      but the University of Michigan Injury Center (MI, USA) hosted a Concussion Summit
      in September 2015 as a means to condense, solidify and disseminate what is
      currently known on the topic. Areas for discussion included concussion incidence
      and prevention, diagnosis and management, legislation and education, legal and
      social aspects and future directions. A summary of those presentations are
      included within.

PMID- 30202566
TI  - Prevalence of traumatic brain injury and mental health problems among individuals
      within the criminal justice system.
AB  - Traumatic brain injury (TBI) is associated with increased aggression and
      antisocial behavior. This review examined existing literature regarding TBI
      prevalence and associated adverse mental health among individuals within the
      criminal justice system. TBI prevalence varied between 12 and 82% for youths, and
      23 and 87% for adults. TBI was associated with a range of negative outcomes,
      particularly substance abuse. However, confounding factors, including differing
      control groups, lack of information for timing and severity of TBI, and use of
      self-report measures for TBI history made it difficult to determine whether TBI
      was a risk factor. Future research should eliminate or counter for these
      confounds, to provide accurate prevalence rates of TBI and the direction of
      association between TBI and offending behaviors.

PMID- 30202568
TI  - Educating the masses: suggestions for improving online concussion information via
      the mainstream media.

PMID- 30202569
TI  - Wearable sensing and mobile devices: the future of post-concussion monitoring?

PMID- 30202567
TI  - Genetic findings in sport-related concussions: potential for individualized
      medicine?
AB  - Concussion is a traumatic transient disturbance of the brain. In sport, the
      initial time and severity of concussion is known giving an opportunity for
      subsequent analysis. Variability in susceptibility and recovery between
      individual athletes depends, among other parameters, on genetic factors. The
      genes-encoding polypeptides that determine incidence, severity and prognosis for
      concussion are the primary candidates for genetic analysis. Genetic polymorphisms
      in the genes contributing to plasticity and repair (APOE), synaptic connectivity
      (GRIN2A), calcium influx (CACNA1E), uptake and deposit of glutamate (SLC17A7) are
      potential biomarkers of concussion incidence and recovery rate. With catalogued
      genetic variants, prospective genotyping of athletes at the beginning of their
      career will allow medical professionals to improve concussion management and
      return-to-play decisions.

PMID- 30202570
TI  - Neuropsychiatric aspects of concussion: acute and chronic sequelae.
AB  - Concussion - also known as mild traumatic brain injury - is a transient
      disturbance of neurological function resulting from traumatic forces imparted to
      the brain that often produce cognitive, behavioral and systemic symptoms. In this
      review of the literature, we discuss the pathophysiology of both acute and
      chronic neuropsychiatric sequelae of concussions, followed by a brief overview of
      evaluation and management of these sequelae.

PMID- 30202572
TI  - A review of the validity of computerized neurocognitive assessment tools in mild
      traumatic brain injury assessment.
AB  - Computerized neurocognitive assessment tools (NCATs) offer potential advantages
      over traditional neuropsychological tests in postconcussion assessments. However,
      their psychometric properties and clinical utility are still questionable. The
      body of research regarding the validity and clinical utility of NCATs suggests
      some support for aspects of validity (e.g., convergent validity) and some ability
      to distinguish between concussed individuals and controls, though there are still
      questions regarding the validity of these tests and their clinical utility,
      especially outside of the acute injury timeframe. In this paper, we provide a
      comprehensive summary of the existing validity literature for four commonly used
      and studied NCATs (automated neuropsychological assessment metrics, CNS vital
      signs, cogstate and immediate post-concussion and cognitive testing) and lay the
      groundwork for future investigations.

PMID- 30202573
TI  - Animal models of chronic traumatic encephalopathy.
AB  - Repeated head impacts have been suggested to be associated with the development
      of the neurodegenerative disorder, chronic traumatic encephalopathy (CTE). CTE is
      characterized by the accumulation of hyperphosphorylated tau within the brain,
      with accompanying cognitive and behavioral deficits. How a history of repeated
      head impacts can lead to the later development of CTE is not yet known, and as
      such appropriate animal models are required. Over the last decade a number of
      rodent models of repeated mild traumatic brain injury have been developed that
      are broadly based on traditional traumatic brain injury models, in controlled
      cortical impact, fluid percussion and weight drop models, with adaptations to
      allow for better modeling of the mechanical forces associated with concussion.

PMID- 30202571
TI  - Pathological vascular and inflammatory biomarkers of acute- and chronic-phase
      traumatic brain injury.
AB  - Given the demand for developing objective methods for characterizing traumatic
      brain injury (TBI), research dedicated to evaluating putative biomarkers has
      burgeoned over the past decade. Since it is critical to elucidate the underlying
      pathological processes that underlie the higher diverse outcomes that follow
      neurotrauma, considerable efforts have been aimed at identifying biomarkers of
      both the acute- and chronic-phase TBI. Such information is not only critical for
      helping to elucidate the pathological changes that lead to poor long-term
      outcomes following TBI but it may also assist in the identification of possible
      prevention and interventions for individuals who sustain head trauma. In the
      current review, we discuss the potential role of vascular dysfunction and chronic
      inflammation in both acute- and chronic-phase TBI, and we also highlight existing
      studies that have investigated inflammation biomarkers associated with poorer
      injury outcome.

PMID- 30202574
TI  - Googling concussion care in the USA: a critical appraisal of online concussion
      healthcare providers.
AB  - Aim: To examine the online personnel and practice profiles of concussion
      healthcare providers in the USA. Methods: We conducted independent, blinded,
      Google Internet searches for concussion healthcare providers using the terms
      'concussion clinic' and 'concussion program' and each American state and
      completed a critical appraisal of healthcare personnel and services at these
      websites. Results: A total of 184 concussion healthcare providers were
      identified. Despite offering care to traumatic brain injury (TBI) patients,
      access to professionals with expertise in TBI including neuropsychologists
      (40.8%), neurologists (33.7%) and neurosurgeons (21.7%) was variable across
      sites. Conclusion: Concussion healthcare in the USA is presently delivered by a
      range of healthcare professionals with varying levels of training in TBI offering
      a variety of services.

PMID- 30202575
TI  - Potential for use of creatine supplementation following mild traumatic brain
      injury.
AB  - There is significant overlap between the neuropathology of mild traumatic brain
      injury (mTBI) and the cellular role of creatine, as well as evidence of neural
      creatine alterations after mTBI. Creatine supplementation has not been researched
      in mTBI, but shows some potential as a neuroprotective when administered prior to
      or after TBI. Consistent with creatine's cellular role, supplementation reduced
      neuronal damage, protected against the effects of cellular energy crisis and
      improved cognitive and somatic symptoms. A variety of factors influencing the
      efficacy of creatine supplementation are highlighted, as well as avenues for
      future research into the potential of supplementation as an intervention for
      mTBI. In particular, the slow neural uptake of creatine may mean that greater
      effects are achieved by pre-emptive supplementation in at-risk groups.

PMID- 30202577
TI  - Auditory comprehension performance of college students with and without sport
      concussion on Computerized-Revised Token Test Subtest VIII.
AB  - Aim: Auditory comprehension (AC) and visually assessed cognitive functions were
      compared in early stage postconcussed (PC) athletes and healthy controls using
      the Subtest VIII of the Computerized-Revised Token Test (C-RTT) and Immediate
      Postconcussion Assessment and Cognitive Test (ImPACT). Results: As compared with
      healthy controls (n = 30), PC subjects (n = 30) had significantly lower C-RTT
      efficiency scores (p = 0.018), and lower ImPACT scores; total symptom score (p =
      0.000.), verbal memory (p = 0.000), visual memory (p = 0.000), visual motor speed
      (p = 0.000) and reaction time (p = 0.004) in this post-test only matched subject
      design. Impulse Control was not significant (p = 0.613). Multiple regression and
      ANOVA indicated an association with reaction time only (p = 0.012) for the PC
      subjects. After controlling for reaction time, a significant difference in AC
      remained. Conclusion: The relationship between AC and other visually assessed
      cognitive functions was inconsistent suggesting that the C-RTT and ImPACT
      assessed different functional systems.

PMID- 30202578
TI  - Helmets in women's lacrosse: what the evidence shows.

PMID- 30202579
TI  - Understanding the effects of mild traumatic brain injury on the pupillary light
      reflex.
AB  - The pupillary light reflex represents an optimal visual system to investigate and
      exploit in the mild traumatic brain injury (mTBI) population. Static and dynamic
      aspects of the pupillary light reflex were investigated objectively and
      quantitatively in the mTBI population. Pupillary responsivity was found to be
      significantly delayed, slowed and reduced, but symmetrical in nature, and with a
      smaller baseline diameter, as compared with normals. Several pupillary parameters
      also discriminated between those with versus without photosensitivity. Thus,
      dynamic pupillometry provides several objective biomarkers for the presence of
      mTBI and photosensitivity, gives insight into the global sites of neurological
      dysfunction and possible related mechanisms, and should result in improved
      patient care.

PMID- 30202576
TI  - White matter changes in patients with mild traumatic brain injury: MRI
      perspective.
AB  - This review focuses on white matter (WM) changes in mild traumatic brain injury
      (mTBI) as assessed by multimodal MRI. All the peer reviewed publications on WM
      changes in mTBI from January 2011 through September 2016 are included in this
      review. This review is organized as follows: introduction to mTBI, the basics of
      multimodal MRI techniques that are potentially useful for probing the WM
      integrity, summary and critical evaluation of the published literature on the
      application of multimodal MRI techniques to assess the changes of WM in mTBI, and
      correlation of MRI measures with behavioral deficits. The MRI-pathology
      correlation studies based on preclinical models of mTBI are also reviewed.
      Finally, the author's perspective of future research directions is described.

PMID- 30202581
TI  - Concussion management knowledge among residents and students and how to improve
      it.
AB  - Aim: Recognition and management of concussion is an area of growing importance.
      The objective was to measure concussion knowledge among residents and medical
      students (MS). Methods: Baseline knowledge was assessed by a standardized
      questionnaire. Control group (family medicine [FM], pediatric medicine [PM] and
      emergency medicine) residents were given reading material, and intervention group
      rotated in a clinic (sports medicine residents and MS). Subjects were retested
      after 36.82 (16.1) days. Pre- and post-intervention test scores were compared.
      Results: The average baseline knowledge scores were 79.2% for emergency medicine
      residents, 61.4% for FM, 68.5% for PM, 71.7% for sports medicine residents and
      68.0% for MS. Knowledge increase for control group was 1.16% compared with 14.41%
      for the clinical rotation group (p < 0.0001). Conclusion: PM and FM residents can
      benefit from more focused education about concussion.

PMID- 30202580
TI  - The role of early intervention in improving the level of activities and
      participation in youths after mild traumatic brain injury: a scoping review.
AB  - Mild traumatic brain injury in children can lead to persistent cognitive and
      physical symptoms which can have a negative impact on activities and
      participation in school and at play. Preventive treatment strategies are
      preferred because these symptoms are often not recognized and therefore not
      treated adequately. In this review clinical studies investigating interventions
      directed at pediatric mild traumatic brain injury are summarized, and clinical
      recommendations and directions for the future are provided. Results show that the
      literature is scarce and more high quality studies are needed. Information and
      education about the injury and its consequences are recommended, with additional
      follow-up consultation, including individualized advice and reassurance. The
      interventions should be family-centered and, ideally, the return to activity and
      participation should be graded and done step-by-step.

PMID- 30202582
TI  - Evidence of dynamic visual acuity impairment in asymptomatic mixed martial arts
      fighters.
AB  - Aim: The purpose of this study was to determine the amount of visual acuity loss
      with head movement in actively training mixed martial arts (MMA) fighters.
      Methods: Vestibulo-ocular reflex function of 22 asymptomatic, male MMA fighters
      (age = 29.2 +/- 5.1) was assessed by taking the difference between static visual
      acuity and the dynamic visual acuity test, in both yaw and pitch planes. Results:
      The mean static visual acuity testing logMAR was -0.173 (standard deviation [SD]
      = 0.114). Mean dynamic visual acuity test values decreased with head movement to
      0.196 logMAR (SD = 0.103) in yaw; p < 0.001, and to 0.283 logMAR (SD = 0.133) in
      pitch; p < 0.001. Conclusion: MMA fighters had a decay, beyond normal ranges, in
      visual acuity during head movement. These decreases may suggest vestibulo-ocular
      reflex impairment and were unrelated to self-reported concussion history. These
      results should be cautiously interpreted since there was not a control group.

PMID- 30202584
TI  - Concussion in motorsport: incidence, awareness and future directions.

PMID- 30202583
TI  - Understanding blast-induced neurotrauma: how far have we come?
AB  - Blast injuries, including blast-induced neurotrauma (BINT), are caused by blast
      waves generated during an explosion. Accordingly, their history coincides with
      that of explosives. Hence, it is intriguing that, after more than 1000 years of
      using explosives, our understanding of the pathological consequences of blast and
      body/brain interactions is extremely limited. Postconflict recovery mechanisms
      seemingly include the suppression of painful experiences, such as explosive
      injuries. Unfortunately, ignoring the knowledge generated by previous generations
      of scientists retards research progress, leading to superfluous and repetitive
      studies. This article summarizes clinical and experimental findings published
      about blast injuries and BINT following the wars of the 20th and 21th centuries.
      Moreover, it offers a personal view on potential factors interfering with the
      progress of BINT research working toward providing better diagnosis, treatment
      and rehabilitation for military personnel affected by blast exposure.

PMID- 30202586
TI  - Microcavitation: the key to modeling blast traumatic brain injury?

PMID- 30202585
TI  - Feasibility of using normobaric hypoxic stress in mTBI research.
AB  - Studies of mild traumatic brain injury (mTBI) recovery generally assess patients
      in unstressed conditions that permit compensation for impairments through
      increased effort expenditure. This possibility may explain why a subgroup of
      individuals report persistent mTBI symptoms yet perform normally on objective
      assessment. Accordingly, the development and utilization of stress paradigms may
      be effective for enhancing the sensitivity of mTBI assessment. Previous studies,
      discussed here, indirectly but plausibly support the use of normobaric hypoxia as
      a stressor in uncovering latent mTBI symptoms due to the overlapping
      symptomatology induced by both normobaric hypoxia and mTBI. Limited studies by
      our group and others further support this plausibility through proof-of-concept
      demonstrations that hypoxia reversibly induces disproportionately severe
      impairments of oculomotor, pupillometric, cognitive and autonomic function in
      mTBI individuals.

PMID- 30202588
TI  - Efficacy of a repeat testing protocol for cognitive fatigue assessment: a
      preliminary study in postconcussive syndrome participants.
AB  - Aim: A small but notable number of individuals who suffer a concussion report
      ongoing cognitive difficulties. This preliminary study investigated the efficacy
      of repetitive test application to discern cognitive impairment in those with
      ongoing symptoms. Methods: Participants (n = 17) with continuing self-reported
      symptoms following a concussion (~9 months postinjury) were compared with 17 age
      group matched controls for working memory and word-list learning. Results: Both
      groups performed similarly after the first trial for both assessments. However,
      in subsequent trials, the postconcussion group performed significantly worse than
      controls. Discussion: While further studies to understand the mechanisms are
      warranted, data from this preliminary study suggest that a repetitive test
      application may be useful to discern cognitive fatigue in individuals who report
      ongoing concerns following a concussion.

PMID- 30202587
TI  - Neurometabolic indicators of mitochondrial dysfunction in repetitive mild
      traumatic brain injury.
AB  - Mild traumatic brain injury (mTBI) is a significant national health concern and
      there is growing evidence that repetitive mTBI (rmTBI) can cause long-term change
      in brain structure and function. The mitochondrion has been suggested to be
      involved in the mechanism of TBI. There are noninvasive methods of determining
      mitochondrial dysfunction through biomarkers and spectroscopy. Mitochondrial
      dysfunction has been implicated in a variety of neurological consequences
      secondary to rmTBI through activation of caspases and calpains. The purpose of
      this review is to examine the mechanism of mitochondrial dysfunction in rmTBI and
      its downstream effects on neuronal cell death, axonal injury and blood-brain
      barrier compromise.

PMID- 30202589
TI  - Big Data in traumatic brain injury; promise and challenges.
AB  - Traumatic brain injury (TBI) is a spectrum disease of overwhelming complexity,
      the research of which generates enormous amounts of structured, semi-structured
      and unstructured data. This resulting big data has tremendous potential to be
      mined for valuable information regarding the "most complex disease of the most
      complex organ". Big data analyses require specialized big data analytics
      applications, machine learning and artificial intelligence platforms to reveal
      associations, trends, correlations and patterns not otherwise realized by current
      analytical approaches. The intersection of potential data sources between
      experimental TBI and clinical TBI research presents inherent challenges for
      setting parameters for the generation of common data elements and to mine
      existing legacy data that would allow highly translatable big data analyses. In
      order to successfully utilize big data analyses in TBI, we must be willing to
      accept the messiness of data, collect and store all data and give up causation
      for correlation. In this context, coupling the big data approach to established
      clinical and pre-clinical data sources will transform current practices for
      triage, diagnosis, treatment and prognosis into highly integrated evidence-based
      patient care.

PMID- 30202590
TI  - Understanding the endocannabinoid system as a modulator of the trigeminal pain
      response to concussion.
AB  - Post-traumatic headache is the most common symptom of postconcussion syndrome and
      becomes a chronic neurological disorder in a substantial proportion of patients.
      This review provides a brief overview of the epidemiology of postconcussion
      headache, research models used to study this disorder, as well as the proposed
      mechanisms. An objective of this review is to enhance the understanding of how
      the endogenous cannabinoid system is essential for maintaining the balance of the
      CNS and regulating inflammation after injury, and in turn making the
      endocannabinoid system a potential modulator of the trigeminal response to
      concussion. The review describes the role of endocannabinoid modulation of pain
      and the potential for use of phytocannabinoids to treat pain, migraine and
      concussion.

PMID- 30202591
TI  - Understanding the interplay between mild traumatic brain injury and cognitive
      fatigue: models and treatments.
AB  - Nearly 2 million traumatic brain injuries occur annually, most of which are mild
      (mTBI). One debilitating sequela of mTBI is cognitive fatigue: fatigue following
      cognitive work. Cognitive fatigue has proven difficult to quantify and study, but
      this is changing, allowing models to be proposed and tested. Here, we review
      evidence for four models of cognitive fatigue, and relate them to specific
      treatments following mTBI. The evidence supports two models: cognitive fatigue
      results from the increased work/effort required for the brain to process
      information after trauma-induced damage; and cognitive fatigue results from sleep
      disturbances. While there are no evidence-based treatments for fatigue after
      mTBI, some pharmacological and nonpharmacological treatments show promise for
      treating this debilitating problem. Future work may target the role of genetics,
      neuroinflammation and the microbiome and their role in complex cognitive
      responses such as fatigue.

PMID- 30202594
TI  - A comparison of emergency department medical records to parental self-reporting
      of traumatic brain injury symptoms.
AB  - Aim: Studies have shown Emergency Department (ED) recording of traumatic brain
      injury (TBI) cases to be poor. Methods: Parents of children aged 2-12 who
      attended an ED with injury to the head completed a concussion checklist which was
      compared with medical records. Results: ED medical records commonly used head
      injury (HI), concussion, minor-HI and mild-HI without distinction between TBI and
      superficial HI. Recalled symptoms included vomiting, blurred vision and headaches
      versus headaches, fatigue and feeling sick from parents who reported more
      concussive symptoms. More cases of TBI were identifiable from parental recall
      compared with medical records, which recorded fewer symptoms for diagnosis,
      prognosis and statistical reporting of TBI. Conclusion: Clear guidelines need to
      be implemented to improve retrospective diagnosis for incidence gathering and
      future clinical use.

PMID- 30202592
TI  - Academic outcomes and accommodations following adolescent sport-related
      concussion: a pilot study.
AB  - Aim: The purpose of this study was to examine academic achievement, absenteeism
      and school accommodations following adolescent sport-related concussion (SRC).
      Methods: A case-series was conducted among grade 8-12 students who suffered an
      SRC. The primary outcomes were change in pre- and post-concussion overall, core
      report card grade point average (GPA) and absenteeism due to concussion. The most
      helpful school accommodations were tabulated. Results: Pre- and post-concussion
      GPA was obtained from 33 students - 16 (48%) developed persistent post-concussion
      symptoms (symptoms lasting >4 weeks). There was no significant difference in pre-
      and post-concussion grades among students with a SRC for overall (p = 0.75) or
      core (p = 0.56) GPA. The median number of missed school days was 4 (interquartile
      range [IQR]: 2-8). Allowing for physical and cognitive rest was identified as the
      most helpful accommodation (30%). Conclusion: Larger studies should investigate
      the role that school accommodations and development of persistent post-concussion
      symptoms have on academic outcomes.

PMID- 30202593
TI  - Sex & gender considerations in concussion research.
AB  - The study of concussion, a common form of mild traumatic brain injury, has
      received increased notice over the last decade. Recently, more researchers have
      been addressing the historic paucity of attention over sex and gender influences
      on recovery outcomes after concussion. This development has led to exciting
      progress in our understanding of concussion incidence and outcomes. In this
      review, we will report on new findings from varying studies on sex differences in
      the epidemiology of concussion and clinical manifestations of mild traumatic
      brain injury/concussion, further discussing some key issues related to the
      integration of sex and gender in concussion research in a broad range of
      contexts, with recommendations to guide future research, along with sex- and
      gender-sensitive policy considerations.

PMID- 30202595
TI  - The role and diagnostic significance of cellular barriers after concussive head
      trauma.
AB  - The onset of concussive head trauma often triggers an intricate sequence of
      physical consequences and pathophysiological responses. These sequelae can be
      acute (i.e., hematoma) or chronic (i.e., autoimmune response, neurodegeneration,
      etc.), and may follow traumas of any severity. A critical factor for
      prognostication of postconcussion outcome is the pathophysiological response of
      cellular barriers, which can be measured by several biomarkers of the acute and
      chronic postinjury phases. We present herein a review on the postconcussion
      mechanisms of the blood-brain barrier, as well as the diagnostic/prognostic
      approaches that utilize differential biomarker expression across this boundary.
      We discuss the role of the blood-saliva cellular barrier as a regulatory filter
      for brain-derived biomarkers in blood, and its implications for saliva-based
      diagnostic assays.

PMID- 30202598
TI  - Discharge pathways and relapse following treatment from early intervention in
      psychosis services.
AB  - Background: Early intervention in psychosis (EIP) services are the dominant
      service model in the treatment of first-episode psychosis. They are a time
      limited intervention and little is known about discharge destinations and
      outcomes once EIP treatment has concluded. Aims: To understand discharge pathways
      and predictors of relapse in an EIP service. Method: We collected data on all
      patients with an electronic health record treated by EIP services in Oxford
      Health NHS Foundation Trust in the UK between 12 January 2006 and 7 March 2017 (n
      = 701). Our primary outcomes were discharge destination at end of treatment and
      relapse. Results: Most patients (83.5%) were discharged to primary care. Transfer
      to secondary care was associated with previous in-patient admissions (odds ratio
      (OR) = 1.92, 95% CI 1.54-2.39) and longer EIP treatment (OR = 1.04, 95% CI 1.03
      1.06). Relapse rate was highest shortly after leaving EIP services. Relapse was
      associated with transfer to secondary care (hazard ratio (HR) = 2.75, 95% CI 1.75
      4.31), higher deprivation (HR = 1.03, 95% CI, 1.01-1.05), a substance misuse
      disorder (HR = 1.81, 95% CI 1.01-3.26) and a comorbid diagnosis of a personality
      disorder (HR = 2.96, 95% CI 1.39-6.29). Conclusions: Most patients treated by the
      EIP service in Oxfordshire did not receive ongoing mental healthcare from
      secondary mental health services. We identified high deprivation and those with
      substance misuse problems or personality disorders as EIP populations with a high
      risk of relapse. Declaration of interest: None.

PMID- 30202597
TI  - Persistence of anxiety symptoms after elective caesarean delivery.
AB  - Background: In the UK, 11.8% of expectant mothers undergo an elective caesarean
      section (ELCS) representing 92 000 births per annum. It is not known to what
      extent this procedure has an impact on mental well-being in the longer term.
      Aims: To determine the prevalence and postpartum progression of anxiety and
      depression symptoms in women undergoing ELCS in Wales. Method: Prevalence of
      depression and anxiety were determined in women at University Hospital Wales
      (2015-16; n = 308) through completion of the Edinburgh Postnatal Depression Scale
      (EPDS; >=13) and State-Trait Anxiety Inventory (STAI; >=40) questionnaires 1 day
      prior to ELCS, and three postpartum time points for 1 year. Maternal
      characteristics were determined from questionnaires and, where possible,
      confirmed from National Health Service maternity records. Results: Using these
      criteria the prevalence of reported depression symptoms was 14.3% (95% CI 10.9
      18.3) 1 day prior to ELCS, 8.0% (95% CI 4.2-12.5) within 1 week, 8.7% (95% CI 4.2
      13.8) at 10 weeks and 12.4% (95% CI 6.4-18.4) 1 year postpartum. Prevalence of
      reported anxiety symptoms was 27.3% (95% CI 22.5-32.4), 21.7% (95% CI 15.8-28.0),
      25.3% (95% CI 18.5-32.7) and 35.1% (95% CI 26.3-44.2) at these same stages.
      Prenatal anxiety was not resolved after ELCS more than 1 year after delivery.
      Conclusions: Women undergoing ELCS experience prolonged anxiety postpartum that
      merits focused clinical attention. Declaration of interest: None.

PMID- 30202596
TI  - Using concurrent gait and cognitive assessments to identify impairments after
      concussion: a narrative review.
AB  - Understanding how a concussion affects an individual is oftentimes difficult for
      clinicians due to the varying symptom profiles reported by the patient and the
      multifaceted and heterogeneous nature of the injury. Accordingly, the
      interpretation of postconcussion performance can be challenging, because many
      different testing paradigms have been reported as potentially useful in the
      literature. Among the types of tests clinicians use to understand how concussion
      affects an individual, both gait and neurocognitive evaluations have demonstrated
      utility. Our purpose is to describe how combined gait and cognitive (i.e., dual
      task), as well as single-task gait and computerized neurocognitive examinations
      can assist clinical decision-making.

PMID- 30202599
TI  - Psychological interventions for bipolar disorder in low- and middle-income
      countries: systematic review.
AB  - Background: Adjunctive psychological interventions for bipolar disorder have
      demonstrated better efficacy in preventing or delaying relapse and improving
      outcomes compared with pharmacotherapy alone. Aims: To evaluate the efficacy of
      psychological interventions for bipolar disorder in low- and middle-income
      countries. Method: A systematic review was conducted using PubMed, PsycINFO,
      Medline, EMBASE, Cochrane database for systematic review, Cochrane central
      register of controlled trials, Latin America and Caribbean Center on Health
      Science Literature and African Journals Online databases with no restriction of
      language or year of publication. Methodological heterogeneity of studies
      precluded meta-analysis. Results: A total of 18 adjunctive studies were
      identified: psychoeducation (n = 14), family intervention (n = 1), group
      cognitive-behavioural therapy (CBT) (n = 2) and group mindfulness-based cognitive
      therapy (MBCT) (n = 1). In total, 16 of the 18 studies were from upper-middle
      income countries and none from low-income countries. All used mental health
      specialists or experienced therapists to deliver the intervention. Most of the
      studies have moderately high risk of bias. Psychoeducation improved treatment
      adherence, knowledge of and attitudes towards bipolar disorder and quality of
      life, and led to decreased relapse rates and hospital admissions. Family
      psychoeducation prevented relapse, decreased hospital admissions and improved
      medication adherence. CBT reduced both depressive and manic symptoms. MBCT
      reduced emotional dysregulation. Conclusions: Adjunctive psychological
      interventions alongside pharmacotherapy appear to improve the clinical outcome
      and quality of life of people with bipolar disorder in middle-income countries.
      Further studies are required to investigate contextual adaptation and the role of
      non-specialists in the provision of psychological interventions to ensure
      scalability and the efficacy of these interventions in low-income country
      settings. Declaration of interest: None.

PMID- 30202600
TI  - Trauma-intrusive hallucinations and the dissociative state.
AB  - Background: Research has supported a model of dissociation mediating the
      experience of hearing voices in traumatised individuals. Aims: To further
      understand this model by examining subtypes of the dissociative experience
      involved in trauma-intrusive hallucinations. Method: The study involved four
      hospitals, 11 psychiatrists and 69 participants assessed using the Psychotic
      Symptoms Rating scale, the PTSD Symptoms Scale Interview and the Dissociative
      Subtype of PTSD Score. Results: In total, 59% (n = 41) of the participants heard
      voices and they were compared with the 41% (n = 28) who did not. The severity of
      PTSD symptoms did not predict experience of hearing voices. Regression analysis
      indicated that two scales of dissociation (derealisation/depersonalisation and
      loss of awareness) were equally good predictors of the extent of hearing voices.
      Adding other possible predictors (age of trauma <18, sexual violence) was
      relevant but did not enhance the prediction. Conclusions: This research supports
      the proposal that trauma-intrusive voices are mediated by symptoms of
      dissociation. The supported model describes general, rather than trauma specific,
      symptoms of dissociation mediating the experience of hearing voices. The concept
      of anchoring is discussed and suggests a potential treatment strategy, which
      could be useful in the clinical management of hearing voices. Declaration of
      interest: None.

PMID- 30202601
TI  - Characteristics of patients expressing an interest in ketamine treatment: results
      of an online survey.
AB  - Background: Off-label ketamine treatment has shown acute antidepressant effects
      that offer hope for patients with therapy-resistant depression. However, its
      potential for integration into treatment algorithms is controversial, not least
      because the evidence base for maintenance treatment with repeated ketamine
      administration is currently weak. Ketamine is also a drug of misuse, which has
      raised concerns regarding the target population. Little is known about which
      patients would seek ketamine treatment if it were more widely available. Aims: To
      explore some of the characteristics of the patients actively seeking ketamine
      treatment. Method: An online survey containing questions about duration of
      current depressive episode, number of antidepressants used and other comments was
      completed by patients who were exploring the internet regarding the possibility
      of ketamine for depression. Results: Of the 1088 people who registered their
      interest, 93.3% reported depression, 64.3% reported a chronic course of their
      symptoms and in the past 10 years, 86.3% had tried at least two antidepressants.
      Desperation was a common theme, but this appeared to be competently expressed. A
      small minority (<8%) reported experience of illegal ketamine use. Conclusions: It
      cannot be ruled out that patients with different degrees of treatment resistance
      and comorbidities will seek treatment with ketamine. This stresses the urgency to
      perform larger randomised controlled trials as well as to systematically monitor
      outcomes and adverse effects of ketamine, that is currently prescribed off-label
      for patients in need. Declaration of interest: R.M. is consulting and is
      Principal Investigator for Janssen trials of esketamine and is consulting for
      Eleusis.

PMID- 30202603
TI  - Heat-not-burn cigarettes heat up controversy.

PMID- 30202604
TI  - Spiral scanning imaging and quantitative calculation of the 3-dimensional screw
      shaped bone-implant interface on micro-computed tomography.
AB  - Purpose: Bone-to-implant contact (BIC) is difficult to measure on micro-computed
      tomography (CT) because of artifacts that hinder accurate differentiation of the
      bone and implant. This study presents an advanced algorithm for measuring BIC in
      micro-CT acquisitions using a spiral scanning technique, with improved
      differentiation of bone and implant materials. Methods: Five sandblasted, large
      grit, acid-etched implants were used. Three implants were subjected to surface
      analysis, and 2 were inserted into a New Zealand white rabbit, with each tibia
      receiving 1 implant. The rabbit was sacrificed after 28 days. The en bloc
      specimens were subjected to spiral (SkyScan 1275, Bruker) and round (SkyScan
      1172, SkyScan 1275) micro-CT scanning to evaluate differences in the images
      resulting from the different scanning techniques. The partial volume effect (PVE)
      was optimized as much as possible. BIC was measured with both round and spiral
      scanning on the SkyScan 1275, and the results were compared. Results: Compared
      with the round micro-CT scanning, the spiral scanning showed much clearer images.
      In addition, the PVE was optimized, which allowed accurate BIC measurements to be
      made. Round scanning on the SkyScan 1275 resulted in higher BIC measurements than
      spiral scanning on the same machine; however, the higher measurements on round
      scanning were confirmed to be false, and were found to be the result of artifacts
      in the void, rather than bone. Conclusions: The results of this study indicate
      that spiral scanning can reduce metal artifacts, thereby allowing clear
      differentiation of bone and implant. Moreover, the PVE, which is a factor that
      inevitably hinders accurate BIC measurements, was optimized through an advanced
      algorithm.

PMID- 30202602
TI  - Retina and glaucoma: surgical complications.
AB  - Background: The close structural and microcirculatory co-relation between
      anterior and posterior segments of eye make them very vulnerable to complications
      when one of them is affected surgically. With the advent of anti-fibrotic agents
      in the management of glaucoma, the rates of vitreoretinal complications have
      become more frequent. Main body: Common retinal complications after glaucoma
      surgeries include choroidal detachment; ocular decompression retinopathy;
      haemorrhagic choroidal detachment; hypotony maculopathy; malignant glaucoma;
      vitreous haemorrhage; bleb endophthalmitis; retinal detachment. Similarly,
      intraocular pressure rise is often noted after scleral buckle; pars plana
      vitrectomy; intravitreal gas injection; silicone oil injection; intravitreal
      steroid injection. Conclusion: The article provides some insight into some of the
      complications after glaucoma and retina surgeries, including the pathogenetic
      mechanisms behind each complication and available management options.

PMID- 30202605
TI  - Factors affecting treatment outcomes in patients with oral lichen planus lesions:
      a retrospective study of 113 cases.
AB  - Purpose: Oral lichen planus (OLP) is a chronic oral mucosal disease that has been
      recognized as an immune condition. The purpose of this study was to evaluate
      factors affecting the clinical outcomes of topical corticosteroid application on
      OLP lesions using dexamethasone gargle and ointment. Methods: The charts of
      patients who were clinically diagnosed with OLP and treated with dexamethasone
      from July 2003 to August 2017 at the Section of Dentistry of Seoul National
      University Bundang Hospital were thoroughly evaluated to identify subjects who
      were suitable for this retrospective study. For each patient, age at the index
      date, gender, medical history, and dental records related to OLP lesions and
      dexamethasone treatment were reviewed. Results: In total, 113 of the 225 patients
      were included in the present study. Among them, 79 patients were female (69.9%)
      and 34 were male (30.1%), with a mean age of 57.6 years. The average duration of
      dexamethasone treatment was 4.7 months and the mean follow-up period was 2.24
      years. Improvements were observed within 1 year after dexamethasone treatment in
      most cases, and 17.7% of patients had a new OLP lesion after treatment. New OLP
      lesions were more frequently gingival than mucosal, although mucosal OLP lesions
      were more common than gingival OLP lesions in all age groups. In age- and gender
      adjusted multivariate logistic regression, a history of malignant disease was
      found to be a significant factor affecting the formation of new lesions. Gingival
      OLP lesions and intermittent use of dexamethasone showed near-significant
      associations. In Kaplan-Meier failure analysis, history of malignancy, menopausal
      status, age, and the site of the OLP lesion were significant factors affecting
      clinical outcomes. Conclusions: The treatment outcomes of OLP were significantly
      influenced by age, history of malignancy, menopausal status, and the site of the
      OLP lesion, but not by factors related to dexamethasone treatment.

PMID- 30202607
TI  - Alveolar ridge preservation with a collagen material: a randomized controlled
      trial.
AB  - Purpose: Resorption of the alveolar bone is an unavoidable consequence of tooth
      extraction when appropriate alveolar ridge preservation (ARP) measures are not
      taken. The objective of this trial was to test the hypothesis that dimensional
      changes in the alveolar bone after tooth extraction would be reduced by inserting
      an equine collagen membrane and a collagen cone to fill and seal the alveolus (as
      ARP), in comparison to extraction with untreated alveoli. Methods: In this
      randomized clinical trial, 31 patients were directly treated with the collagen
      material after extraction of a tooth from the maxilla (the ARP group). Twenty
      nine patients served as the control group. After extraction, no further treatment
      (i.e., no socket preservation measures) was performed in the control group.
      Changes in the alveolar process immediately after extraction and after an 8 (+/
      1)-week healing period were evaluated 3-dimensionally. Blinded analyses were
      performed after superimposing the data from the digitalized impressions and
      surfaces generated by cone-beam computed tomography. Results: Both the ARP and
      control groups showed a reduction of bone in the alveolar area after tooth
      extraction. However, significantly less bone resorption was detected in the
      clinically relevant buccal region in the ARP group. The median bone reduction was
      1.18 mm in the ARP group and 5.06 mm in the control group (P=0.03). Conclusions:
      The proposed hypothesis that inserting a combination material comprising a
      collagen cone and membrane would lead to a difference in alveolar bone
      preservation can be accepted for the clinically relevant buccal distance. In this
      area, implantation of the collagen material led to significantly less alveolar
      bone resorption. German Clinical Trials Register at www.drks.de, DRKS00004769.

PMID- 30202606
TI  - Effects of platelet-rich plasma on tooth replantation in dogs: a histologic and
      histomorphometric analysis.
AB  - Purpose: The purpose of this study was to evaluate the effects of platelet-rich
      plasma (PRP) on periodontal healing of replanted root surfaces in dogs
      histologically and histomorphometrically. Methods: A total of 36 roots of
      mandibular incisors and premolars from 6 mongrel dogs were used. The roots were
      randomly divided into 3 groups: 1) a positive control group (n=12), in which the
      periodontal ligament (PDL) and cementum were retained and the roots were soaked
      in saline; 2) a negative control group (n=12), in which the PDL and cementum were
      removed and the roots were soaked in saline; and 3) an experimental group (n=12),
      in which the PDL and cementum were removed and the roots were soaked in PRP.
      After soaking the root surfaces, the extracted roots were replanted into the
      extraction sockets. The roots were covered using a coronally repositioned flap.
      Results: Histologically, irregular-thickness PDL-like and cementum-like tissues
      were observed in the 4-week experimental group and the positive control group.
      PDL-like tissue and cementum-like tissue with a more uniform thickness were
      observed at 8 weeks. In the negative control group, PDL-like tissue and cementum
      like tissue were rarely found, and root resorption and ankylosis were observed.
      In the cross-sectional histomorphometric analysis, the experimental group
      demonstrated a higher rate of formation of cementum-like tissue and a lower tooth
      ankylosis rate than the positive and negative control groups at 4 and 8 weeks.
      Although there was a significant difference in the tooth ankylosis rate and the
      formation of cementum-like tissue across the 3 groups (P<0.05), no statistical
      significance was observed between any pair of groups (P>0.017). Conclusions:
      Applying PRP to root surfaces during tooth replantation in dogs can reduce tooth
      ankylosis and increase PDL-like and cementum-like tissue formation.

PMID- 30202608
TI  - Association of chairside salivary aMMP-8 findings with periodontal risk
      assessment parameters in patients receiving supportive periodontal therapy.
AB  - Purpose: The aim of this retrospective cross-sectional study was to evaluate
      whether salivary findings of active matrix-metalloproteinase 8 (aMMP-8) chairside
      (point of care; POC) tests were associated with periodontal risk assessment
      parameters in patients receiving supportive periodontal therapy (SPT). Methods: A
      total of 125 patients receiving regular SPT were included, and their records were
      examined. The following inclusion criteria were used: a diagnosis of chronic
      periodontitis, at least 1 non-surgical periodontal treatment (scaling and root
      planning) with following regular SPT (minimum once a year), at least 6 remaining
      teeth, and clinical and aMMP-8 findings that were obtained at the same
      appointment. In addition to anamnestic factors (e.g., smoking and diabetes), oral
      hygiene indices (modified sulcus bleeding index [mSBI] and approximal plaque
      index), periodontal probing depth simultaneously with bleeding on probing, and
      dental findings (number of decayed, missing, and filled teeth) were recorded.
      Salivary aMMP-8 levels were tested using a commercial POC test system
      (Periomarker, Hager & Werken, Duisburg, Germany). Statistical analysis was
      performed using the t-test, Mann-Whitney U test, Fisher's exact test, and chi2
      test, as appropriate (P<0.05). Results: Only the mSBI was significantly
      associated with positive salivary aMMP-8 findings (aMMP-8 positive: 27.8%+/-20.9%
      vs. aMMP-8 negative: 18.0%+/-14.5%; P=0.017). No significant associations were
      found between aMMP-8 and smoking, diabetes, periodontal parameters, or parameters
      related to the maintenance interval (P>0.05). Conclusions: Salivary aMMP-8
      chairside findings were not associated with common parameters used for
      periodontal risk assessment in patients receiving SPT. The diagnostic benefit of
      POC salivary aMMP-8 testing in risk assessment and maintenance interval
      adjustment during SPT remains unclear.

PMID- 30202609
TI  - Real-time PCR quantification of 9 periodontal pathogens in saliva samples from
      periodontally healthy Korean young adults.
AB  - Purpose: Few studies have examined periodontal pathogens from saliva samples in
      periodontally healthy young adults. The purposes of this study were to determine
      the prevalence of periodontopathic bacteria and to quantify periodontal pathogens
      in saliva samples using real-time polymerase chain reaction (PCR) assays in
      periodontally healthy Korean young adults under 35 years of age. Methods: Nine
      major periodontal pathogens were analyzed by real-time PCR in saliva from 94
      periodontally healthy young adults. Quantification of Aggregatibacter
      actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia, Treponema
      denticola, Prevotella intermedia, Fusobacterium nucleatum, Campylobacter rectus,
      Peptostreptococcus anaerobius, and Eikenella corrodens was performed by DNA copy
      number measurement. Results: F. nucleatum and E. corrodens were detected in all
      subjects; the numbers of positive samples were 87 (92.6%), 91 (96.8%), and 90
      (95.7%) for P. gingivalis, P. anaerobius, and C. rectus, respectively. Other
      pathogens were also detected in periodontally healthy subjects. Analysis of DNA
      copy numbers revealed that the most abundant periodontal pathogen was F.
      nucleatum, which was significantly more prevalent than all other bacteria
      (P<0.001), followed by P. anaerobius, P. gingivalis, E. corrodens, C. rectus, and
      T. denticola. There was no significant difference in the prevalence of each
      bacterium between men and women. The DNA copy number of total bacteria was
      significantly higher in men than in women. Conclusions: Major periodontal
      pathogens were prevalent in the saliva of periodontally healthy Korean young
      adults. Therefore, we suggest that the development of periodontal disease should
      not be overlooked in periodontally healthy young people, as it can arise due to
      periodontal pathogen imbalance and host susceptibility.

PMID- 30202610
TI  - Evaluation of Corneal Biomechanical Changes After Collagen Crosslinking in
      Patients with Progressive Keratoconus by Ocular Response Analyzer.
AB  - Objectives: To evaluate corneal biomechanics before and after collagen
      crosslinking (CXL) in patients with progressive keratoconus. Materials and
      Methods: In this prospective study, CXL was performed under topical anesthesia
      after removal of the epithelium (epi-off technique) by applying ultraviolet A
      (UVA) light at a wavelength of 365 nm and power of 3 mW/cm2 or 5.4 joule/cm2.
      Isoosmolar 0.1% riboflavin solution was administered before and during UVA
      irradiation. In addition to ophthalmologic examination, ocular response analyzer
      measurements were performed pre- and postoperatively. Corneal hysteresis (CH),
      corneal resistance factor (CRF), corneal compensated intraocular pressure
      (IOPcc), Goldmann-correlated intraocular pressure (IOPg), and central corneal
      thickness (CCT) were recorded. Results: The study included 35 eyes of 30 patients
      with progressive keratoconus. The mean age was 28.2+/-6.5 years and postoperative
      follow-up time was 20.2+/-14.7 months (range: 6-74 months). The mean CH was
      8.60+/-1.23 mmHg preoperatively, 8.96+/-2.05 mmHg in the early postoperative
      period (1-6 months), (p=0.28) and 8.96+/-1.28 mmHg in the late postoperative
      period (10-29 months) (p=0.48). Mean CRF was 7.13+/-1.50 mmHg preoperatively,
      8.48+/-2.16 mmHg in the early postoperative period (p=0.009), and 7.71+/-1.29
      mmHg in the late postoperative period (p=0.40). Mean IOPcc was 12.78+/-2.34 mmHg
      preoperatively, 15.38+/-4.21 mmHg in the early postoperative period (p=0.12) and
      13.68+/-3.61 mmHg in the late postoperative period (p=0.48). Mean IOPg was 9.56+/
      2.73 mmHg preoperatively, 13.01+/-4.45 mmHg in the early postoperative period
      (p=0.046), and 10.86+/-3.47 mmHg in the late postoperative period (p=0.44). Mean
      CCT was 484.43+/-41.26 um preoperatively, 474.16+/-64.74 um in the early
      postoperative period (p=0.70), and 470.38+/-33.64 um in late postoperative period
      (p=0.71). Conclusion: CXL is a treatment modality believed to affect corneal
      biomechanics in keratoconus, but the results of larger patient series with longer
      follow-up periods may enable a better evaluation.

PMID- 30202611
TI  - Does Long-term Soft Contact Lens Wear Affect Corneal and Anterior Chamber
      Parameters?
AB  - Objectives: To assess the long-term effects of soft contact lenses (SCL) on the
      cornea and anterior chamber by topography. Materials and Methods: Thirty-nine
      eyes of 22 healthy patients were included in this prospective study. Changes in
      corneal and anterior chamber parameters before and after 12 months of daily SCL
      use (Air Optix Aqua, Air Optix Aqua for Astigmatism, Acuvue Oasys and Acuvue
      Oasys for Astigmatism) were evaluated with Pentacam (Oculus, Germany). Results:
      Best corrected visual acuity with toric SCL was significantly better compared to
      spectacles in the toric SCL group (0.98+/-0.34 vs 0.94+/-0.72, p=0.004). None of
      the corneal (horizontal and vertical keratometry, corneal volume, anterior and
      posterior corneal astigmatism, corneal pachymetry of apex and thinnest location)
      and anterior chamber (anterior chamber depth, volume and angle) parameters showed
      a statistically significant change after long-term daily wear of SCLs.
      Conclusion: The results of this study revealed that long-term wear of current
      high oxygen permeable and relatively low modulus silicone hydrogel SCLs does not
      impact cornea and anterior chamber morphology or volumetric parameters.
      Furthermore, toric silicone hydrogel SCLs can provide better visual performance
      than spectacles.

PMID- 30202612
TI  - Corneal Biomechanical Properties of Keratoconic Eyes Following Penetrating
      Keratoplasty.
AB  - Objectives: To investigate the corneal biomechanical properties of keratoconic
      eyes following penetrating keratoplasty (PKP). Materials and Methods: Thirty-five
      patients (70 eyes) were enrolled to this prospective study. Operated and
      contralateral keratoconic eyes were defined as Group 1 and 2, respectively. All
      patients underwent ophthalmological examination and measurements of corneal
      biomechanical properties by Ocular Response Analyzer (ORA), intraocular pressure
      (IOP) by Goldmann applanation tonometry, and central corneal thickness (CCT) by
      Pentacam. Shapiro-Wilk W test was performed to test normality of the data. The
      statistical significance was evaluated with the paired t-test and Wilcoxon signed
      ranks test. Pearson correlation and Spearman rho tests were used for correlation
      analysis. Results: The average age and male/female ratio were 31.34+/-11.65 (15
      60) years and 21/14, respectively. The mean values of the data obtained from
      Group 1 and 2 respectively were: corneal hysteresis (CH): 9.35+/-1.66, 8.18+/
      1.84 mmHg (p=0.013), corneal resistance factor (CRF): 9.48+/-1.96, 7.14+/-2.05
      mmHg (p<0.001), IOPcc: 16.90+/-4.32, 14.26+/-3.69 mmHg (p=0.004), IOPg: 15.45+/
      4.61, 10.91+/-3.97 mmHg (p<0.001), IOPapl: 14.26+/-3.11, 13.09+/-2.54 mmHg
      (p=0.046), and central corneal thickness (CCT): 545.64+/-60.82, 442.60+/-68.14
      MUM (p<0.001). The positive correlation between CH and CRF was moderate (r=0.444)
      in Group 1 and strong (r=0.770) in Group 2. There was a moderate negative
      correlation between CH and IOPcc in both groups (r=-0.426, r=-0.423), but CH was
      not correlated with IOPg or IOPapl in either group. There were weak to strong
      positive correlations between CRF and all IOP values in both groups. There was no
      correlation between CRF and CCT in Group 1 (r=0.075) and a very weak correlation
      in Group 2 (r=0.237). Only IOPcc and IOPg were strongly correlated in both
      groups. Conclusion: Better understanding of corneal biomechanical properties is
      essential for elucidating the pathophysiology and diagnosis of several corneal
      pathologies such as keratoconus. The biomechanical properties of keratoconic eyes
      seem to be closer to normal values after PKP.

PMID- 30202613
TI  - Does Foveal Position Relative to the Optic Disc Affect Optical Coherence
      Tomography Measurements in Glaucoma?
AB  - Objectives: To determine interindividual variability in the angle between the
      anatomic axis connecting the fovea and optic disc center and the horizontal
      meridian using spectral domain optical coherence tomography (OCT). Materials and
      Methods: A total of 260 eyes of 133 subjects (81 women, 52 men) with glaucoma or
      suspected glaucoma were included in the study retrospectively. Fovea-disc angle
      (FoDi angle) measurements, determined as the angle between the horizontal
      meridian passing through the Bruch's membrane opening (BMO) center and the line
      connecting the fovea and BMO center, were recorded from spectral domain-OCT scans
      performed by the same investigator. FoDi angle was defined as negative if the
      fovea was located below the horizontal meridian through the BMO center and
      positive if the fovea was located above it. Results: The mean age of the
      participants was 56.5+/-14.6 years (27-83 years). The mean FoDi angle was -6.43+/
      4.96 degrees  (range: -24.40 degrees  to +11.60 degrees ). Absolute deviation of
      the fovea BMO axis from the horizontal axis was 0-5 degrees  in 83 eyes (31.92%),
      5-10 degrees  in 124 eyes (47.69%), 10-15 degrees  in 41 eyes (15.76%), 15-20
      degrees  in 10 eyes (3.84%), and greater than 20 degrees  in 2 eyes (0.79%).
      Conclusion: Most OCT devices currently used in the treatment and follow-up of
      glaucoma patients provide peripapillary retinal nerve fiber layer (RNFL)
      thickness measurements that are made based on a clinical axis in reference to the
      horizontal meridian passing through the optic disc center. The results of our
      study reveal interindividual variation in FoDi angle as well as intraindividual
      differences in FoDi angle between fellow eyes in the same individual. Disparity
      between clinical and anatomic quadrants could impact RNFL thickness measurements,
      which may lead to errors in the diagnosis of glaucoma.

PMID- 30202614
TI  - A Custom-made Pupillometer System for Characterizing Pupillary Light Response.
AB  - Objectives: This paper presents the design and construction of a viable
      pupillometer system and demonstrates its merits with extensive validation tests.
      Materials and Methods: A web camera was modified by removing its infrared filter
      and mounted on a chin rest. Light emitting diodes (LEDs) operating at infrared
      and visible spectra were integrated to provide background and light stimulus,
      respectively. The LEDs were controlled by a microprocessor board. Stimulation was
      presented using a periodic paradigm with variable period and duty cycle. Videos
      of both pupils were recorded at 30 frames/second and processed offline using
      software developed in-house. The overall system was validated with data gathered
      from individuals with healthy vision under different stimulation paradigms.
      Temporal variations in pupil size were determined and analyzed statistically.
      Results: The analysis revealed that the pupil sizes were accurately measured from
      the video frames provided that reflections from both infrared and visible lights
      remain outside the pupil. The system achieved moderate to excellent repeatability
      scores (87.8 and 86.8% for short 1 second and long 2 second pulses,
      respectively), which demonstrated its effectiveness and confirmed that it can be
      used reliably as a pupillometer. Conclusion: The proposed pupillometer system
      produces useful, quantitative data characterizing pupillary light response.
      However, further development and implementation are needed to potentially turn it
      into a low-cost alternative for other studies involving the autonomic nervous
      system, cognitive function, drug metabolism, pain response, psychology, fatigue,
      and sleep disorders.

PMID- 30202615
TI  - The Effects of Anti-Vascular Endothelial Growth Factor Drugs on Retinal Pigment
      Epithelial Cell Culture.
AB  - Objectives: To assess the effects of anti-vascular endothelial growth factor
      (VEGF) drugs on retinal pigment epithelium cell culture. Materials and Methods:
      Aflibercept (0.5 mg/mL), bevacizumab (0.3125 mg/mL), and ranibizumab (0.125
      mg/mL) were applied to retinal pigment epithelium cell cultures isolated from the
      enucleated eyes of New Zealand white rabbits. Viability, apoptosis,
      proliferation, and senescence of the cells were evaluated in control and drug
      treated cultures at the end of 72 hours. Results: Cells treated with aflibercept
      showed increased viability and decreased apoptosis compared to the control
      culture and both the bevacizumab- and ranibizumab-treated groups (p<0.05).
      Statistically increased apoptosis and decreased viability were found in the
      bevacizumab and ranibizumab-treated groups compared with the control group
      (p<0.05). There were no statistically significant differences in cell
      proliferation and senescence between the groups (p>0.05). Conclusion: Anti-VEGF
      drugs did not affect senescence or proliferation of retinal pigment epithelium
      cells. Aflibercept was found to decrease apoptosis and increase cell viability,
      while ranibizumab and bevacizumab increased apoptosis and reduced cell viability
      in retinal pigment epithelium culture.

PMID- 30202616
TI  - Optical Coherence Tomography Angiography in Glaucoma.
AB  - Optical coherence tomography angiography (OCTA) comprises different OCT-based
      technologies developed for non-invasive assessment and measurement of optic nerve
      head and retinal perfusion. Currently the most clinically established approach is
      based on the split spectrum amplitude decorrelation algorithm, which detects
      moving red blood cells and eliminates all other information. The two main
      clinical fields in which OCTA offers clinically useful information are
      investigation of the macular retina (e.g. in macular degeneration and diabetic
      macular disease) and glaucoma. For glaucoma, the optic nerve head and the
      peripapillary retinal perfusion in the retinal nerve fiber layer, and the
      superficial perifoveal macular vasculature are the areas of interest. This review
      provides a comprehensive summary of the most important current and potential
      future applications of OCTA in glaucoma, but it does not address the
      nonglaucomatous optic nerve head or peripapillary and macular diseases.

PMID- 30202617
TI  - Optic Neuropathy and Macular Ischemia Associated with Neurosarcoidosis: A Case
      Report.
AB  - In this study, we present a case of bilateral optic neuropathy and macular
      ischemia in the right eye associated with neurosarcoidosis. A 26-year-old woman
      presented to our clinic with complaints of bilateral blurred vision. Bilateral
      granulomatous anterior uveitis, vitritis, optic neuropathy, and macular ischemia
      were detected in the right eye in slit-lamp examination. She also reported
      complaints of fever, weakness, sweating, arthralgia, and headache for 2 months.
      She was referred to the pulmonary diseases unit of our hospital due to hilar
      lymphadenopathy seen in her chest x-ray, and biopsies were taken for diagnostic
      purposes. Histological analysis of the mediastinal lymph node biopsies revealed
      chronic, non-caseating, granulomatous inflammation. Furthermore, the patient was
      referred to a neurologist due to concomitant complaint of intense headaches. She
      was diagnosed with neurosarcoidosis supported by findings on cranial magnetic
      resonance imaging and lumbar puncture. She received a 3-day course of high-dose
      (1 g/day) intravenous steroid treatment (methylprednisolone) followed by a
      tapering dose of oral prednisone. The patient began receiving oral methotrexate
      15 mg/week as a steroid-sparing agent. Significant improvement in neurological
      and ophthalmological symptoms occurred in the first week of treatment. In this
      case report, we emphasized that neurosarcoidosis should be included in the
      differential diagnosis of patients with both bilateral optic neuropathy and
      macular ischemia. Furthermore, early diagnosis and timely treatment of
      neurosarcoidosis are important for favorable visual outcomes.

PMID- 30202618
TI  - Possible Association of Papillophlebitis with Guillain-Barre Syndrome: Case
      Report.
AB  - In this case report, we presented a patient with visual deterioration as a result
      of papillophlebitis in the right eye who was later diagnosed with Guillain-Barre
      syndrome (GBS). Upon systemic and laboratory work-up to determine the etiology of
      papillophlebitis, the diagnosis of GBS was made and treatment was initiated
      immediately. The ocular and systemic symptoms resolved quickly after starting
      intravenous immunoglobulin therapy. We present this case to emphasize the
      importance of etiological diagnosis in papillophlebitis and the unusual
      presentation of GBS.

PMID- 30202619
TI  - Intravitreal Aflibercept as an Adjunct to Systemic Therapy in a Case of Choroidal
      Neovascular Membrane Associated with Sympathetic Ophthalmia.
AB  - Choroidal neovascular membrane (CNV) is a very rare complication in patients with
      sympathetic ophthalmia. We hereby report a 38-year-old man who developed a type 2
      CNV in his only seeing (left) eye while under systemic steroid treatment.
      Systemic therapy was revised and a total of 5 intravitreal aflibercept injections
      (2 mg each) were administered over a period of 8 months. Good anatomic and
      functional outcome was noted at the last visit. Anti-vascular endothelial growth
      factor injection may be an important adjunct to systemic therapy in eyes with
      with sympathetic ophthalmia-associated CNV.

PMID- 30202620
TI  - Familial Exudative Retinopathy: A Case and Family Analysis.
AB  - Familial exudative vitreoretinopathy (FEVR) is a rare inherited disorder of
      retinal angiogenesis. A 49-year-old male patient was referred to our clinic for
      retinal vascular occlusion. His history, clinical findings, and fundus
      fluorescein angiography findings were evaluated. Family members were called and
      eye examinations were performed. Our patient was not born preterm and he reported
      decreased visual acuity after a traffic accident during childhood. He had laser
      treatment when he was 12 years old and again 1 month before our examination. He
      also had laser-assisted in situ keratomileusis surgery for both eyes in 2002. On
      examination, his visual acuity was 0.4 in the right eye and 0.3 in the left eye.
      He had cortical cataract in both eyes. Macula OCT revealed macular contour
      irregularity due to epiretinal membrane in his right eye and minimal perifoveal
      thinning in his left eye. On fundus photography, straightening of the retinal
      vessels, macular dragging, retinal folds on temporal retina, preretinal fibrosis,
      and laser spots were seen. FFA revealed avascular retinal areas with incomplete
      laser spots in the temporal, inferior, and superior parts of retina. He also had
      neovascularization with leakage in the temporal retina of his right eye. The
      patient's brother, who was also born at full term, also had excessive branching
      of the vascular structures in the temporal peripheral retina, non-perfused cord
      vessels and avascular areas. In light of all these findings, we diagnosed our
      patient with Stage 2A FEVR and his brother with Stage 1 FEVR. In summary, FEVR is
      a clinically diagnosed disease. Because FEVR is inherited and potentially sight
      threatening, family examination is helpful and important so that affected family
      members can be diagnosed and followed up.

PMID- 30202621
TI  - Reproductive outcomes of office hysteroscopic metroplasty in women with
      unexplained infertility with dysmorphic uterus.
AB  - Objective: The correlation between dysmorphic uterus and infertility still
      remains enigmatic. We evaluated the reproductive outcomes of metroplasty via
      office hysteroscopy in unexplained infertile women with dysmorphic uteri.
      Materials and Methods: In this retrospective cohort study, metroplasty via office
      hysteroscopy using a bipolar system was performed to 272 women with unexplained
      infertility with dysmorphic uteri from January 2013 to January 2016. Of all the
      patients, 162 had primary infertility, and 110 had secondary infertility.
      Results: In the primary infertility group, the clinical pregnancy rate was 45.68%
      (74/162) and the live birth rate was 38.9% (63/162), and in the secondary
      infertility group, the clinical pregnancy rate was 55.45% (61/110) and the live
      birth rate was 49% (54/110) after metroplasty. In the secondary infertility
      group, the miscarriage rate and especially the ectopic pregnancy rate declined
      dramatically [from 84.5% (93/110) to 9.8% (6/61) and from 15.5% (17/110) to 1.6%
      (1/61), respectively] (p<0.01). Conclusion: Reproductive outcome can be impaired
      by Mullerian anomalies, hence, infertile women with dysmorphic uteri should
      undergo hysteroscopy to improve reproductive outcomes. Our study demonstrated
      that office hysteroscopic metroplasty of a dysmorphic uterus might improve
      fertility, particularly in patients with unexplained infertility with dysmorphic
      uteri, which was an ignored factor previously. Office hysteroscopy is an
      alternative option in terms of non-invasive procedure.

PMID- 30202622
TI  - The use of in vitro maturation in stimulated antagonist in vitro fertilization
      cycles of normo-hyperresponder women due to arrested follicular development: A
      rescue procedure.
AB  - Objective: To evaluate the impact of rescue in vitro maturation (IVM) on the
      clinical outcomes of women with arrested follicular development in stimulated in
      vitro fertilization (IVF) cycles. Materials and Methods: This is a retrospective
      review of 13 patients who were evaluated as normo-hyperresponders for ovarian
      stimulation. The main outcome measure was the clinical pregnancy and livebirth
      rates. The purpose of gonadotropin stimulation in patients undergoing IVF is to
      retrieve multiple oocytes by avoiding multifetal gestation and Ovarian
      Hyperstimulation syndrome (OHSS). The ovarian response to stimulation ranges from
      poor response to OHSS, which is related to the follicular number and the dose of
      the gonadotropins used. However, in some cycles of normo-hyperresponder women,
      follicular development decelerates or ceases. Close follow-up in a daily manner
      and increasing the dose of gonadotropins did not change the follicular arrest.
      This clinical situation has two edges; one is cycle cancellation, which has
      undesired psychological outcomes for women and the IVF team, and second one is
      the prolongation of the IVF cycle. For such circumstances, IVM may be a valuable
      option. Stimulated IVF cycles were converted to IVM as a rescue IVM procedure
      following detailed informed consent of the women who were close to cycle
      cancellation. Results: Thirteen 13 IVM cycles and their clinical outcomes are
      presented. Six women achieved pregnancies, but only 4 delivered 5 healthy live
      born. The other two women had biochemical loss during follow-up. Conclusion:
      Based on the data obtained, it can be concluded that gonadotropin-stimulated
      cycles with follicular arrest at the edge of cancellation can be shifted to
      rescue IVM procedures with reasonable clinical outcomes.

PMID- 30202623
TI  - A retrospective comparative study of prednisolone use in antagonist co-treated
      assisted reproductive technology cycles for patients with good prognosis.
AB  - Objective: To investigate the impact of peri-implantation prednisolone use and
      its duration in antagonist co-treated assisted reproductive technology (ART)
      cycles of patients with good prognosis. Materials and Methods: Infertile patients
      treated with gonadotropin-releasing hormone antagonist protocol between January
      2010 and June 2013 were included. The patients in group A (n=196) received no
      prednisolone. The patients in groups B (n=397) and C (n=371) received 5 mg oral
      prednisolone daily, for 4 and 12 days following embryo transfer, respectively.
      The main outcome parameter was live birth rate. Results: The ages of the groups
      were 30.1+/-4.6, 31.5+/-4.5, and 30.9+/-4.7 years, respectively (p=0.163). There
      was no statistically significant difference between the groups regarding cycle
      characteristics. Implantation rates were 20.7%, 24.6%, and 23.8%, respectively
      (p=0.163). Miscarriage rates were 1.5%, 3.5%, and 3.2%, respectively (p=0.859).
      Live birth rates were 28.7%, 29.3%, and 32.8%, respectively (p=0.482).
      Conclusion: Empiric prednisolone administration during the peri-implantation
      period does not seem to have beneficial effects in ART cycles of patients with
      good prognosis.

PMID- 30202624
TI  - Circulating SCUBE1 levels in women with polycystic ovary syndrome.
AB  - Objective: Polycystic ovary syndrome (PCOS) is thought to represent an early
      manifestation of metabolic syndrome, which is associated with cardiovascular
      disease. Signal peptide-CUB (complement C1r/C1s, Uegf, and Bmp1)-epidermal growth
      factor domain-containing protein 1 (SCUBE1) is a platelet activation marker that
      plays important roles in vascular biology and has been closely linked to
      cardiovascular events. In the present study, we investigated SCUBE1 levels in
      lean glucose-tolerant women with PCOS and assessed the possible association
      between SCUBE1 levels and hormonal and metabolic features of women with PCOS.
      Materials and Methods: The study population consisted of 90 lean [body mass index
      (BMI) <25 kg/m2] women who were diagnosed as having PCOS using the Rotterdam
      criteria and 100 age- and BMI-matched healthy controls with no clinical or
      biochemical feature of hyperandrogenism. Glucose tolerance was evaluated in all
      subjects before recruitment using the 2 h 75 g oral glucose tolerance test, and
      only those exhibiting normal glucose tolerance were enrolled. Hormonal and
      metabolic parameters, and serum SCUBE1 levels were evaluated. Results:
      Circulating SCUBE1 levels were significantly higher in women with PCOS than in
      controls (5.9+/-3.9 vs. 4.2+/-1.4 ng/mL, p=0.022). No association between SCUBE1
      level and clinical or biochemical parameters was found in the control or PCOS
      group. Conclusion: SCUBE1 levels are elevated in women with PCOS compared with
      those in healthy controls; thus, this protein may be an early biomarker of
      cardiovascular disease later in life.

PMID- 30202625
TI  - Modified abdominal packing method in "near miss" patients with postpartum
      hemorrhages.
AB  - Objective: To describe a more effective abdominal packing method in patients with
      disseminated intravascular coagulation following peripartum hysterectomy due to
      postpartum hemorrhage (PPH). Materials and Methods: The present retrospective and
      descriptive study was conducted to document six cases with refractory pelvic
      bleeding who underwent a second surgery for PPH between January 2016 and December
      2017 at Istanbul Zeynep Kamil Woman and Children Diseases Training and Research
      Hospital. Results: Karateke packing was performed to control intra-abdominal
      massive hemorrhages of five women who were referred to our clinic due to PPH who
      had undergone peripartum hysterectomy and hypogastric artery ligation but
      hemostasis could not be provided. In addition, a case of hypovolemic shock due to
      placenta percreta rupture in a woman who had also undergone an emergency
      hysterectomy and hypogastric artery ligation, which had failed. Hemostasis was
      provided in all patients. No method-related complication developed. Conclusion:
      Karateke packing is a very easy method to perform, it is more effective than the
      classic abdominal packing technique, with a low complication rate, and most
      importantly, life-saving in patients undergoing a peripartum hysterectomy due to
      PPH and thereafter experiencing diffuse hemorrhage.

PMID- 30202626
TI  - The effect of first trimester hemoglobin levels on pregnancy outcomes.
AB  - Objective: The relationship between hemoglobin levels and pregnancy outcomes is
      still a challenging issue. There is a supported opinion about the increased
      adverse pregnancy outcomes both with low and high hemoglobin levels. In this
      study, we aimed to evaluate this association for first trimester hemoglobin
      levels in a Turkish population. Materials and Methods: In this retrospective
      study, 1306 women who were followed up during their pregnancy and gave birth in
      our clinic were enrolled. The patients were divided into three groups: hemoglobin
      <11 g/dL (n=490), 11<= hemoglobin <13 g/dL (n=673), and hemoglobin >=13 g/dL
      (n=143). The hemoglobin <11 g/dL group was classified into two subgroups as
      hemoglobin <=9 g/dL (n=64) and hemoglobin >9 g/dL (n=426). Demographic
      characteristics, first trimester hemoglobin levels, gestational age at delivery
      and mode, birth weight, Apgar scores, and pregnancy outcomes were recorded and
      compared between the groups. Results: Pregnancy-induced hypertension, preterm
      birth, neonatal intensive care unit admission, birth weight, gestational age at
      delivery, Apgar scores, and postpartum hemorrhage were significantly different
      between the three groups. In the pairwise comparison, gestational age at
      delivery, birth weight, and first minute Apgar scores were higher in the 11<=
      hemoglobin <13 g/dL group, and pregnancy-induced hypertension was more common in
      the hemoglobin >=13 g/dL group as compared with the others. Moreover, the preterm
      delivery rate was highest in the hemoglobin >=13 g/dL (26.6%) group and lowest
      (7.3%) in the 11<= hemoglobin <13 g/dL group. The neonatal intensive care unit
      admission rate was higher both the hemoglobin <11 g/dL and hemoglobin >=13 g/dL
      groups. Postpartum hemorrhage was more common in the hemoglobin <11 g/dL group as
      compared with the other groups. Furthermore, pregnancy-induced hypertension was
      more common in the hemoglobin <=9 g/dL subgroup (p=0.012). Conclusion: In
      conclusion, both low and high hemoglobin levels are related with adverse
      pregnancy outcomes. We suggest that hemoglobin levels must be screened during
      pregnancy to provide maternal and fetal well-being.

PMID- 30202627
TI  - Early-onset neonatal infection in pregnancies with prelabor rupture of membranes
      in Kosovo: A major challenge.
AB  - Objective: Prelabor rupture of membranes (PROM) is a common event in obstetrics
      that has a major impact in pregnancy outcome. This condition is linked to a
      number of pregnancy and birth complications with early-onset neonatal infection
      (EONI) being one of the major threats. This study was undertaken to determine the
      rate of neonatal infection in newborn infants with a maternal history of PROM and
      to evaluate the association of risk factors with neonatal infection following
      PROM. Materials and Methods: A cross-sectional descriptive design was used to
      analyze a population of 200 pregnant women presenting to the Obstetrics and
      Gynecology Tertiary Center in Kosovo (between 2013 and 2015) with PROM who gave
      birth to single newborns. Data including demographic characteristics, neonatal
      outcome, and risk factors for infectious neonatal morbidity were recorded and
      analyzed. Results: The study included 200 pregnant women with PROM and their
      newborns. Participant demographics included: the majority were young, aged
      between 20 and 29 years (67%), primiparous (67.5%), unemployed (92%), completed
      secondary level of education (83%), and with middle socioeconomic status (86%).
      Overall, 13% of the newborns had early-onset neonatal infection, and sepsis was
      proven in 5% of cases. Newborns of mothers with risk factors such as preterm (<37
      weeks) PROM, low gestational weight at birth, prolonged rupture of membranes,
      maternal colonization, and low Appearance, Pulse, Grimace, Activity, Respiration
      score at birth had higher rates of infection compared with newborns of mothers
      without these risk factors. Conclusion: The rate of EONI in pregnancies
      complicated with PROM continues to be a global challenge in perinatology, and as
      this study reports, also a major challenge for Kosovo. Future research, revision
      and improvement on prenatal care and practices, timing of delivery, medical
      treatment, and prophylactic use of antibiotics in PROM are needed to reduce
      rates.

PMID- 30202628
TI  - YKL-40 in the diagnosis, prediction of prognosis, and platinum sensitivity in
      serous epithelial ovarian cancer.
AB  - Objective: To evaluate the use of YKL-40 in the discrimination between benign and
      malignant adnexal mass and to determine its prognostic value in assessing
      residual tumor after primary cytoreduction and platinum sensitivity in serous
      epithelial ovarian carcinoma (EOC). Materials and Methods: During the three years
      from January 2015 to December 2017, a nonconsecutive series of 100 patient (60
      malignant, 40 benign) who underwent surgery for an adnexal mass were enrolled in
      the study. Preoperatively, serum samples were collected for YKL-40 level
      analysis. Results: YKL-40 [receiver operator characteristics (ROC)-area under
      curve (AUC)=0.83] was a significantly better predictor of EOC than cancer antigen
      125 (ROC-AUC=0.75). Using a cut-off for YKL-40 of 47.7 ng/mL had a sensitivity of
      80% and a specificity of 70%. Higher serum YKL-40 levels were associated with
      advanced stage, higher grade, residual tumor after primary cytoreduction and
      recurrence. Platinum-sensitive patients had significantly elevated levels of YKL
      40 compared with platinum-resistant or refractory patients. Conclusion: The
      results obtained from our study support the use of serum YKL-40 for the
      discrimination between malignant and benign ovarian tumors. YKL-40 levels in
      patients with serous EOC may also predict disease residual disease after primary
      cytoreduction and recurrence. Further studies are needed to understand the
      relationship between YKL-40 and platinum sensitivity.

PMID- 30202629
TI  - Women self-reported G-spot existence and relation with sexual function and
      genital perception.
AB  - Objective: Aim of study to determine the existence of the G-spot from the healthy
      women's point of view and to assess the relationship with sexual function and
      genital perception. Materials and Methods: Sexually-active healthy polyclinic
      patients aged between 18 and 54 years (n=309) were classified into three groups
      as group 1 (do not agree, n=90, 29.1%), group 2 (neutral/do not know, n=61,
      19.7%) and group 3 (agree, n=158, 51.1%) with regard to participants' responses
      to a question of "does the G-spot exist." The Female Sexual Function index (FSFI)
      and Female Genital Self-Image scale (FGSIS) were administered to the
      participants. Results: Half of the patients (51.1%, n=151) indicated that the G
      spot exists. The groups were statistically homogeneous in terms of body mass
      index, parity, marital status, number of partners, and sexual orientation
      (p=0.41, p=0.06, p=0.12, p=0.19, p=0.25; respectively). Women with an education
      level of "less than high school" reported the absence of the G-spot significantly
      more often than others, whereas women with an education level of "university and
      higher" reported the presence of the G-spot more often (p<=0.001). Sexual
      dysfunction was found to be more frequent in group 1 when compared with group 3
      (p=0.002, 67.8%, 45.6%). The orgasm subdomain scores of the FSFI and FGSIS total
      scores were significantly higher in group 3 than in group 1 (p<0.001, p=0.041).
      Conclusion: Half of healthy women in the Turkish population believe that the G
      spot exists. Those women showed better scores in sexual functioning and genital
      perception.

PMID- 30202630
TI  - Active management of the third stage of labor: A brief overview of key issues.
AB  - Postpartum hemorrhage is a potentially life-threatening, albeit preventable,
      condition that persists as a leading cause of maternal death. It occurs mostly
      during the third stage of labor, and active management of the third stage of
      labor (AMTSL) can prevent its occurrence. AMTSL is a recommended series of steps,
      including the provision of uterotonic drugs immediately upon fetal delivery,
      controlled cord traction, and massage of the uterine fundus, as developed by the
      World Health Organization. Here, we present current opinion and protocols for
      AMTSL.

PMID- 30202632
TI  - Are complicated monochorionic twins more susceptible to indomethacin-induced
      fetal ductal constriction? Two cases of laser surgery for Twin-Twin Transfusion
      syndrome.
AB  - Indomethacin is a commonly used medication against preterm delivery. Several
      reports of fetal ductal constriction have been described after indomethacin use
      in the literature; however, there are no previously documented reports describing
      an association between Twin-Twin Transfusion syndrome and a constrictor effect of
      indomethacin on the ductus arteriosus. Two patients were referred to our
      department for Twin-Twin Transfusion syndrome and each underwent placental laser
      surgery. Constriction of the ductus arteriosus occurred as early as 20 and 24
      weeks' gestation following maternal use of indomethacin after laser surgery.
      Spontaneous amelioration was observed after discontinuation of the drug. The
      constrictor effect of indomethacin on the ductus arteriosus can be observed even
      after a single dose and as early as 20 weeks of gestation in complicated
      monochorionic twin pregnancies. We emphasize meticulous use of indomethacin in
      complicated monochorionic twin pregnancies because the constrictive effect seems
      to be independent of gestational age.

PMID- 30202631
TI  - Use of a gelatin-thrombin hemostatic matrix in obstetrics and gynecological
      surgery.
AB  - Gelatin-thrombin matrix (GTM) is a hemostatic sealant consisting of bovine
      derived gelatin matrix and human-derived thrombin, combining both mechanical and
      active mechanisms to achieve hemostasis. It was approved by the Food and Drug
      Administration in 1999. GTM has been used by several surgical specialties;
      however, it is a possibly an under-used tool in obstetrics and gynecology. A
      limited number of studies have been performed on its use during laparoscopic
      endometrioma excision and myomectomy. It may prove useful in endometrioma
      excision in reproductive aged women because it is likely to harm ovarian reserve
      less than electrocautery; however, this conclusion needs to be validated. The
      only study on GTM use in myomectomy included 50 women randomized into GTM and
      control groups, and showed decreased blood loss and shorter hospital stays in the
      GTM group. In gynecologic oncology, it was successfully used to reduce lymphocele
      cases in a cohort study. GTM has been used successfully in obstetrics in a
      handful of cases of uncontrolled bleeding from caesarean scar, placental site,
      ectopic pregnancy, rectovaginal hematoma, and venous plexus over the vaginal
      vault after emergency postpartum hysterectomy. Risk of viral transmission is a
      major concern about GTM, yet there are no reports on disease transmission with
      GTM use to date. Rare but serious adverse effects and complications have been
      reported such as fatal or near-fatal thromboembolism and small bowel obstruction.
      Although GTM is mostly a safe product, it is still not free of complications and
      risks. In conclusion, although routine use of GTM cannot be recommended due to
      concerns about its safety, cost, and availability, it may prove useful when
      conventional hemostatic methods such as suturing and electrocauterization fail or
      are not appropriate.

PMID- 30202634
TI  - A comparison of the clinical courses of type 2 diabetic patients whose basal
      insulin preparation was replaced from insulin glargine 100 units/mL to insulin
      glargine biosimilar or 300 units/mL: a propensity score-matched observation
      study.
AB  - Objective: We compared the clinical course of type 2 diabetic patients whose
      basal insulin preparations were replaced from insulin glargine (IGlar) 100
      units/mL (U100) to IGlar biosimilar or IGlar 300 units/mL (U300). Methods: After
      propensity score matching, 34 patients whose basal insulin preparation was
      switched from IGlar U100 to IGlar biosimilar and 102 switched to IGlar U300 were
      observed for 6 months. Results: The HbA1c level and body weight did not change
      significantly after the replacement in the IGlar biosimilar or IGlar U300 groups.
      In the IGlar biosimilar group, the frequency of subjects who experienced
      hypoglycemia after the replacement (12%) was not different from before (12%).
      However, the frequency was significantly lower after the replacement (2%) than
      before (13%) in the IGlar U300 group. The change in the HbA1c level after the
      replacement showed a significant association with the HbA1c level at the baseline
      but not with the kind of IGlar. Hypoglycemia was frequently observed in subjects
      who had experienced hypoglycemia before the replacement. Conclusions: IGlar
      biosimilar and IGlar U300 induced similar HbA1c and body weight changes among
      type 2 diabetic patients. IGlar biosimilar is a suitable option for patients with
      a low risk for hypoglycemia.

PMID- 30202633
TI  - Primitive neuroectodermal tumor of genital tract in hysterectomized patient: A
      case report.
AB  - Primitive neuroectodermal tumors are high-grade malignant neoplasms. These are
      uncommon entities for the female genital tract. The treatment, management and
      follow-up period of Ewing's tumors are not well-defined because of their rarity
      in the genital tract. Surgical debulking is the mainstay treatment in all cases.
      After debulking surgery, patients receive chemotherapy and/or radiotherapy and
      there is a relation between disease stage and survival. Herein, we present a case
      of ovarian primitive neuroectodermal tumor with a review of previously reported
      cases.

PMID- 30202635
TI  - Improving outcomes in the treatment of opioid dependence (IOTOD): reflections on
      the impact of a medical education initiative on healthcare professionals'
      attitudes and clinical practice.
AB  - Since 2011, the annual improving outcomes in the treatment of opioid dependence
      (IOTOD) meeting has brought together a broad range of primarily European
      healthcare professionals as part of an ongoing effort to promote best practice
      for this particularly vulnerable patient population. IOTOD, a comprehensive
      educational initiative, includes the annual Continuing Medical Education (CME)
      accredited IOTOD conference, which is dedicated to measuring practice change and
      outcomes resulting from attendance at its educational sessions. Following each
      session, delegates are asked to vote for or against incorporating specified
      changes into their clinical practice. These "commitments to change" have formed
      one measure of the effectiveness and impact of the IOTOD conference. Here, we
      look at why educational initiatives like the IOTOD conference are valuable,
      examine our methods for conducting a CME-accredited event, and highlight
      individualised treatment plans and delivery. We examine this approach -
      increasingly seen as best practice - as an example of how it may be changing
      attitudes and eventually affecting clinical applications in the field of opioid
      dependence. The measured commitments to change offer insight into HCPs' attitudes
      towards opioid dependence management and show that attitudes towards
      individualised treatment plans seem to be progressively positive, with a general
      consensus to incorporate psychosocial interventions.

PMID- 30202636
TI  - Beyond the Rim: Considering the Micro-Dynamics of CME Accreditation in India.

PMID- 30202637
TI  - Personalized prescription of tyrosine kinase inhibitors in unresectable
      metastatic cholangiocarcinoma.
AB  - Background: Cholangiocarcinoma is an aggressive tumor with poor prognosis. Most
      of the cases are not available for surgery at the stage of the diagnosis and the
      best clinical practice chemotherapy results in about 12-month median survival.
      Several tyrosine kinase inhibitors (TKIs) are currently under investigation as an
      alternative treatment option for cholangiocarcinoma. Thus, the report of
      personalized selection of effective inhibitor and case outcome are of clinical
      interest. Case presentation: Here we report a case of aggressive metastatic
      cholangiocarcinoma (MCC) in 72-year-old man, sequentially treated with two
      targeted chemotherapies. Initially disease quickly progressed during best
      clinical practice care (gemcitabine in combination with cisplatin or
      capecitabine), which was accompanied by significant decrease of life quality.
      Monotherapy with TKI sorafenib was prescribed to the patient, which resulted in
      stabilization of tumor growth and elimination of pain. The choice of the
      inhibitor was made based on high-throughput screening of gene expression in the
      patient's tumor biopsy, utilized by Oncobox platform to build a personalized
      rating of potentially effective target therapies. However, time to progression
      after start of sorafenib administration did not exceed 6 months and the regimen
      was changed to monotherapy with Pazopanib, another TKI predicted to be effective
      for this patient according to the same molecular test. It resulted in disease
      progression according to RECIST with simultaneous elimination of sorafenib side
      effects such as rash and hand-foot syndrome. After 2 years from the diagnosis of
      MCC the patient was alive and physically active, which is substantially longer
      than median survival for standard therapy. Conclusion: This case evidences that
      sequential personalized prescription of different TKIs may show promising
      efficacy in terms of survival and quality of life in MCC.

PMID- 30202638
TI  - Clinical confirmation to demonstrate similarity for a biosimilar pegfilgrastim: a
      3-way randomized equivalence study for a proposed biosimilar pegfilgrastim versus
      US-licensed and EU-approved reference products in breast cancer patients
      receiving myelosuppressive chemotherapy.
AB  - Background: Chemotherapy-induced neutropenia is a common result of
      myelosuppressive chemotherapy treatment. Infections such as febrile neutropenia
      (FN) are sensitive to the duration of neutropenia as well as the depth of
      absolute neutrophil count (ANC) at nadir. Filgrastim, a granulocyte colony
      stimulating factor (G-CSF), can stimulate the function of mature neutrophils.
      Pegfilgrastim, a long-acting form of filgrastim, has been shown to reduce FN to a
      greater extent compared to filgrastim. G-CSF agents have been recommended for
      prophylactic administration with chemotherapy. Apotex developed a proposed
      pegfilgrastim biosimilar. This study was conducted to confirm that no clinically
      meaningful efficacy or safety differences exist between Apotex's proposed
      biosimilar and its reference product. Methods: 589 breast cancer patients were
      randomized and dosed with the proposed pegfilgrastim biosimilar, US-licensed
      pegfilgrastim reference product, or EU-approved pegfilgrastim reference product.
      The primary endpoint assessed was the duration of severe neutropenia (DSN) and
      secondary endpoints included rate of FN and ANC nadir. Results: Data showed that
      the mean DSN, the primary endpoint measured, was comparable across all three
      treatments. The As Treated arm had a 95% confidence interval within the
      equivalence range for the proposed pegfilgrastim biosimilar with the US-licensed
      and EU-approved pegfilgrastim reference products. Secondary endpoints, which
      included depth and peak of ANC nadir, time to ANC recovery post-nadir and rates
      of FN, also showed similarity between the three different treatment groups. The
      adverse event incidence was similar across treatment arms and there were no
      unexpected safety events. Conclusions: Overall, these results show that the
      proposed pegfilgrastim biosimilar is similar to Amgen's US-licensed and EU
      approved pegfilgrastim reference products with regard to the clinical efficacy
      and safety endpoints assessed.Trial registration EMA: European Union Clinical
      Trials Register: (https://www.clinicaltrialsregister.eu/ctr
      search/search?query=eudract_number:2011-002678-21) Eudract # 2011-002678-21
      Registered: 01/10/2012.

PMID- 30202640
TI  - Integrative taxonomy of the genus Pseudostegana (Diptera, Drosophilidae) from
      China, with descriptions of eleven new species.
AB  - The genus Pseudostegana (Okada, 1978) currently contains thirty-nine described
      species. A number of Pseudostegana were collected from the fieldwork in
      southwestern China from 2010 to 2017. Eleven new species were discovered and are
      described from southwestern China: Pseudostegana alpina Zhang & Chen, sp. nov.;
      Pseudostegana amnicola Zhang & Chen, sp. nov.; Pseudostegana amoena Zhang & Chen,
      sp. nov.; Pseudostegana mailangang Zhang & Chen, sp. nov.; Pseudostegana meiduo
      Zhang & Chen, sp. nov.; Pseudostegana meiji Zhang & Chen, sp. nov.; Pseudostegana
      mystica Zhang & Chen, sp. nov.; Pseudostegana stictiptrata Zhang & Chen, sp.
      nov.; Pseudostegana stigmatptera Zhang & Chen, sp. nov.; Pseudostegana ximalaya
      Zhang & Chen, sp. nov. and Pseudostegana zhuoma Zhang & Chen, sp. nov. A key to
      all Chinese Pseudostegana species based on morphological characters is provided.
      Two mitochondrial loci (COI and ND2) and one nuclear locus (28S rRNA) were
      sequenced for the Pseudostegana specimens, and Bayesian and RAxML concatenated
      analyses were run. Molecular species delimitation is performed using the distance
      based automatic barcode gap discovery (ABGD) method. Molecular data support the
      morphological characteristics observed among these Chinese species and confirm
      the new species as being distinctly different.

PMID- 30202639
TI  - Genetic variability of Akhal-Teke horses bred in Italy.
AB  - Background: The Akhal-Teke horse (AKH) is native of the modern Turkmenistan area.
      It was introduced in Italy from 1991 to 2000 mainly as an endurance horse. This
      paper characterizes the genetic variability of the whole Italian AKH horse
      population and evaluates their inbreeding level by analyzing microsatellite
      markers and mitochondrial D-Loop sequences. Methods: Seventeen microsatellite
      marker loci were genotyped on 95 DNA samples from almost all the AKH horses bred
      in Italy in the last 20 years. Standard genetic variability measures (Ho, He,
      FIS) were compared against the same variables published on other eight AKH
      populations. In addition, 397 bp of mtDNA D-loop region were sequenced on a sub
      group of 22 unrelated AKH out of the 95 sampled ones, and on 11 unrelated Arab
      horses. The haplotypes identified in the Italian population were aligned to
      sequences of AKH (56), Arab (five), Caspian Pony (13), Przewalskii (two) and Barb
      (15) horses available in GenBank. The Median Joining Network (MJN), Principal
      Component Analysis (PCA) and Neighbor-joining (NJ) tree were calculated on the
      total 126 sequences. Results: Nucleic markers showed a high degree of
      polymorphism (Ho = 0.642; He = 0.649) and a low inbreeding level (FIS = 0.016) in
      Italian horses, compared to other AKH populations (ranged from -0.103 AKH from
      Estonia to 0.114 AKH from Czech Republic). High variability was also recorded in
      the D-Loop region. 11 haplotypes were identified with haplotype diversity (hd),
      nucleotide diversity (pi) and average number of nucleotide differences (k) of
      0.938, 0.021 and 6.448, respectively. When all the 126 D-Loop sequences were
      compared, 51 haplotypes were found, and four were here found only in the Italian
      AKH horses. The 51 haplotypes were conformed to eight recognized mtDNA
      haplogroups (A, C, F, G, L, M, P and Q) and confirmed by MJN analysis, Italian
      horses being assigned to five haplogroups (A, C, G, L and M). Using a PCA
      approach to the same data, the total haplotypes were grouped into two clusters
      including A+C+M+P and G+F haplogroups, while L and Q haplogroups remained
      ungrouped. Finally, the NJ algorithm effectively discretizes only the L
      haplogroup. All the above data univocally indicate good genetic variability and
      accurate management of the Akhal-Teke population in Italy.

PMID- 30202641
TI  - Identification of candidate genes and proteins in aging skeletal muscle
      (sarcopenia) using gene expression and structural analysis.
AB  - Sarcopenia is an age-related disease characterized by the loss of muscle mass and
      muscle function. A proper understanding of its pathogenesis and mechanisms may
      lead to new strategies for diagnosis and treatment of the disease. This study
      aims to discover the underlying genes, proteins, and pathways associated with
      sarcopenia in both genders. Integrated analysis of microarray datasets has been
      performed to identify differentially expressed genes (DEGs) between old and young
      skeletal muscles. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia
      of Genes and Genomes (KEGG) pathway enrichment analysis were then performed to
      uncover the functions of the DEGs. Moreover, a protein-protein interaction (PPI)
      network was constructed based on the DEGs. We have identified 41,715 DEGs,
      including 19 downregulated and 41,696 upregulated ones, in men. Among women,
      3,015 DEGs have been found, with 2,874 of them being upregulated and 141
      downregulated genes. Among the top up-regulated and downregulated genes, the
      ribosome biogenesis genes and genes involved in lipid storage may be closely
      related to aging muscles in men and women respectively. Also, the DEGs were
      enriched in the pathways including those of ribosome and Peroxisome proliferator
      activated receptor (PPAR) in men and women, respectively. In the PPI network,
      Neurotrophic Receptor Tyrosine Kinase 1 (NTRK1), Cullin 3 (CUL3) and P53 have
      been identified as significant hub proteins in both genders. Using the integrated
      analysis of multiple gene expression profiles, we propose that the ribosome
      biogenesis genes and those involved in lipid storage would be promising markers
      for sarcopenia in men and women, respectively. In the reconstructed PPI network,
      neurotrophic factors expressed in skeletal muscle are essential for motoneuron
      survival and muscle fiber innervation during development. Cullin E3 ubiquitin
      ligase (Cul3) is an important component of the ubiquitin-proteasome system-it
      regulates the proteolysis. P53 is recognized as a central regulator of the cell
      cycle and apoptosis. These proteins, which have been identified as the most
      significant hubs, may be involved in aging muscle and sarcopenia.

PMID- 30202642
TI  - Investigating individual and social behaviour of the Northern bald ibis
      (Geronticus eremita): behavioural variety and welfare.
AB  - The Northern bald ibis (Geronticus eremita) (NBI) is one of the most threatened
      birds in the world. Intense conservation efforts have been undertaken and several
      research projects on the species are being done in Morocco and in Europe.
      Observing animal behaviour has been proved to be an efficient and non-invasive
      technique to assess the animal welfare, with the performance of a wide array of
      natural behaviours being one of the mostly used indicators of good mental and
      physical well-being. The aim of this study was to investigate the behaviour of a
      flock of 14 zoo-living NBI of different ages. The study focused on the variety of
      species-specific individual and social behaviours, in the light of reintroduction
      of the study juveniles in the wild. Per subject, 20 10-min. sessions were done. A
      continuous focal animal sampling method was used to collect individual and social
      behaviours. Behavioural data have been compared between adults and juveniles.
      Moreover, a Behavioural Variety Index (BVI) has been proposed and calculated
      based on previous literature describing natural ibis behaviours. The BVI might
      help in the evaluation of the variety of behaviours performed by each individual
      and the monitoring of the diversity of the behavioural repertoire of zoo animals.
      Our results showed that the birds performed species-specific behaviours and no
      abnormal behaviour was reported. Moreover, the BVI highlighted a good behavioural
      variety as each bird performed approximately 78% of the natural behaviours
      described in the Northern bald ibis and in close relative species. Our findings
      seem to suggest the presence of qualitative and quantitative similarities between
      the behavioural repertoires of the study ibises and those described in wild
      conspecifics, suggesting a good welfare of the colony. Finally, the BVI proposed
      in the current study seems to be a useful and practical tool to test behavioural
      diversity in zoo animals.

PMID- 30202643
TI  - Changes in metabolic profiling of sugarcane leaves induced by endophytic
      diazotrophic bacteria and humic acids.
AB  - Plant growth-promoting bacteria (PGPB) and humic acids (HA) have been used as
      biostimulants in field conditions. The complete genomic and proteomic
      transcription of Herbaspirillum seropedicae and Gluconacetobacter diazotrophicus
      is available but interpreting and utilizing this information in the field to
      increase crop performance is challenging. The identification and characterization
      of metabolites that are induced by genomic changes may be used to improve plant
      responses to inoculation. The objective of this study was to describe changes in
      sugarcane metabolic profile that occur when HA and PGPB are used as
      biostimulants. Inoculum was applied to soil containing 45-day old sugarcane
      stalks. One week after inoculation, the methanolic extracts from leaves were
      obtained and analyzed by gas chromatography coupled to time-of-flight mass
      spectrometry; a total of 1,880 compounds were observed and 280 were identified in
      all samples. The application of HA significantly decreased the concentration of
      15 metabolites, which generally included amino acids. HA increased the levels of
      40 compounds, and these included metabolites linked to the stress response
      (shikimic, caffeic, hydroxycinnamic acids, putrescine, behenic acid, quinoline
      xylulose, galactose, lactose proline, oxyproline and valeric acid) and cellular
      growth (adenine and adenosine derivatives, ribose, ribonic acid and citric acid).
      Similarly, PGPB enhanced the level of metabolites identified in HA-treated soils;
      e.g., 48 metabolites were elevated and included amino acids, nucleic acids,
      organic acids, and lipids. Co-inoculation (HA+PGPB) boosted the level of 110
      metabolites with respect to non-inoculated controls; these included amino acids,
      lipids and nitrogenous compounds. Changes in the metabolic profile induced by
      HA+PGPB influenced both glucose and pentose pathways and resulted in the
      accumulation of heptuloses and riboses, which are substrates in the nucleoside
      biosynthesis and shikimic acid pathways. The mevalonate pathway was also
      activated, thus increasing phytosterol synthesis. The improvement in cellular
      metabolism observed with PGPB+HA was compatible with high levels of vitamins.
      Glucuronate and amino sugars were stimulated in addition to the products and
      intermediary compounds of tricarboxylic acid metabolism. Lipids and amino acids
      were the main compounds induced by co-inoculation in addition to antioxidants,
      stress-related metabolites, and compounds involved in cellular redox. The primary
      compounds observed in each treatment were identified, and the effect of co
      inoculation (HA+PGPB) on metabolite levels was discussed.

PMID- 30202645
TI  - Shrub encroachment into grasslands: end of an era?
AB  - Shifts in the abundance of grasses and woody plants in drylands have occurred
      several times during the Holocene. However, our understanding of the rates and
      dynamics of this state-change in recent decades is limited to scattered studies
      conducted at disparate spatial and temporal scales; the potential misperceptions
      of shrub cover change could be remedied using cross spatiotemporal scale analyses
      that link field observations, repeat ground-level photography and remote sensing
      perspectives. The study was conducted across a semi-arid landscape in southern
      Arizona. Local data from long-term transects revealed three distinct
      chronological phases of shrub cover change: expansion (1961-1991, 0.7% y-1),
      decline (1992-1997, -2.3% y-1) and stabilization (1998-2012, 22-25% with no net
      cover change). Twenty-eight years (1984-2011) of broad-scale Landsat Thematic
      Mapper assessments confirm that shrub cover has been relatively stable in recent
      decades regardless of grazing regimes and landforms with the exception of the
      proliferation of succulents at lower elevations (verified by repeat photography
      acquired in 1987 and 2015) where the physical environment is the harshest,
      reflecting elevated temperature and winter precipitation deficit. Warmer, drier
      future climates are predicted to reduce woody plant carrying capacity and promote
      a shift to xerophytic succulents.

PMID- 30202644
TI  - Molecular identification of avian influenza virus subtypes H5N1 and H9N2 in birds
      from farms and live bird markets and in respiratory patients.
AB  - Background: Avian influenza viruses (AIVs) have been endemic in Egypt since 2006,
      and the co-circulation of high-pathogenic avian influenza H5N1 and low-pathogenic
      avian influenza H9N2 subtypes in poultry has been reported; therefore, Egypt is
      considered a hotspot for the generation of new subtypes and genotypes. We aimed
      to characterize AIVs circulating on commercial farms and in live bird markets
      (LBMs) during the winters of 2015 and 2016 in the study area and to identify H5N1
      and H9N2 viruses in respiratory patients. Methods: In total, 159 samples were
      collected from ducks, pigeons and quails on farms (n = 59) and in LBMs (n = 100)
      and screened by real-time RT-PCR for H5N1 and H9N2 subtypes. Clinical and
      postmortem examination was carried out on birds from the farms. Positive H5N1
      samples were sequenced and analysed for mutations. Tracheal swabs were also
      collected from 89 respiratory patients admitted to respiratory hospitals in the
      same study area. Results: Overall, H5N1 was identified in 13.6% of birds from
      farms, while it was detected in 17% of birds in LBMs. Subtype H9N2 was only
      identified from pigeons on farms (6.5%) and LBMs (11.4%). Sequencing of the
      haemagglutination gene (HA) in nine representative H5N1 isolates revealed a multi
      basic amino acid motif at the cleavage site (321-PQGEKRRKKR/GLF-333), which is
      characteristic of highly pathogenic AIV, in five of our isolates, while the other
      four isolates showed an amino acid substitution (Q322K) at this cleavage site to
      make it (321-P K GEKRRKKR/GLF-333). All the isolates belonged to clade 2.2.1.2,
      and a comparison of HA sequences at the amino acid level showed 98.8-100%
      homology among the nine isolates, while they showed 94.1-96.1% identity with
      reference strains and the commonly used vaccine strain in Egypt. Out of 89
      respiratory patients, 3.4% were positive for H5N1 and no patients were positive
      for H9N2. Discussion: Our results indicated the circulation of the endemic H5N1
      and H9N2 viruses among poultry in 2015 and 2016. Birds on farms and in LBMs are
      reservoirs playing a role in the dissemination of the virus and producing a
      public health risk. The application of proper hygienic measures in farms and LBMs
      to control the exposure of birds and humans to the source of infection along with
      continuous monitoring of the circulating viruses will provide information on
      understanding the evolution of the viruses for vaccine studies.

PMID- 30202646
TI  - Episodix: a serious game to detect cognitive impairment in senior adults. A
      psychometric study.
AB  - Introduction: Assessment of episodic memory is traditionally used to evaluate
      potential cognitive impairments in senior adults. The present article discusses
      the capabilities of Episodix, a game to assess the aforementioned cognitive area,
      as a valid tool to discriminate among mild cognitive impairment (MCI),
      Alzheimer's disease (AD) and healthy individuals (HC); that is, it studies the
      game's psychometric validity study to assess cognitive impairment. Materials and
      Methods: After a preliminary study, a new pilot study, statistically significant
      for the Galician population, was carried out from a cross-sectional sample of
      senior adults as target users. A total of 64 individuals (28 HC, 16 MCI, 20 AD)
      completed the experiment from an initial sample of 74. Participants were
      administered a collection of classical pen-and-paper tests and interacted with
      the games developed. A total of six machine learning classification techniques
      were applied and four relevant performance metrics were computed to assess the
      classification power of the tool according to participants' cognitive status.
      Results: According to the classification performance metrics computed, the best
      classification result is obtained using the Extra Trees Classifier (F1 = 0.97 and
      Cohen's kappa coefficient = 0.97). Precision and recall values are also high,
      above 0.9 for all cognitive groups. Moreover, according to the standard
      interpretation of Cohen's kappa index, classification is almost perfect (i.e.,
      0.81-1.00) for the complete dataset for all algorithms. Limitations: Weaknesses
      (e.g., accessibility, sample size or speed of stimuli) detected during the
      preliminary study were addressed and solved. Nevertheless, additional research is
      needed to improve the resolution of the game for the identification of specific
      cognitive impairments, as well as to achieve a complete validation of the
      psychometric properties of the digital game. Conclusion: Promising results
      obtained about psychometric validity of Episodix, represent a relevant step ahead
      towards the introduction of serious games and machine learning in regular
      clinical practice for detecting MCI or AD. However, more research is needed to
      explore the introduction of item response theory in this game and to obtain the
      required normative data for clinical validity.

PMID- 30202648
TI  - Selecting appropriate variables for detecting grassland to cropland changes using
      high resolution satellite data.
AB  - Grassland is one of the most represented, while at the same time, ecologically
      endangered, land cover categories in the European Union. In view of the global
      climate change, detecting its change is growing in importance from both an
      environmental and a socio-economic point of view. A well-recognised tool for Land
      Use and Land Cover (LULC) Change Detection (CD), including grassland changes, is
      Remote Sensing (RS). An important aspect affecting the accuracy of change
      detection is finding the optimal indicators of LULC changes (i.e., variables).
      Inappropriately selected variables can produce inaccurate results burdened with a
      number of uncertainties. The aim of our study is to find the most suitable
      variables for the detection of grassland to cropland change, based on a pair of
      high resolution images acquired by the Landsat 8 satellite and from the vector
      database Land Parcel Identification System (LPIS). In total, 59 variables were
      used to create models using Generalised Linear Models (GLM), the quality of which
      was verified through multi-temporal object-based change detection. Satisfactory
      accuracy for the detection of grassland to cropland change was achieved using all
      of the statistically identified models. However, a three-variable model can be
      recommended for practical use, namely by combining the Normalised Difference
      Vegetation Index (NDVI), Wetness and Fifth components of Tasselled Cap.
      Increasing number of variables did not significantly improve the accuracy of
      detection, but rather complicated the interpretation of the results and was less
      accurate than detection based on the original Landsat 8 images. The results
      obtained using these three variables are applicable in landscape management,
      agriculture, subsidy policy, or in updating existing LULC databases. Further
      research implementing these variables in combination with spatial data obtained
      by other RS techniques is needed.

PMID- 30202649
TI  - Physical, mechanical and energy characterization of wood pellets obtained from
      three common tropical species.
AB  - Background: The need for energy sources with low greenhouse gas emissions and
      sustainable production encourages the search for alternative biomass sources.
      However, the use of biomass fuels faces the problem of storage, transport and
      lower energy densities. Low-density values can negatively affect energy density,
      leading to an increase in transportation and storage costs. Use of pellets as
      alternative biomass source is a way to reduce the volume of biomass by
      densification, which improves their energy quality. They are produced by diverse
      biomass resources and mainly from wood materials. In all cases, it is important
      to evaluate the fuel characteristics, to determine their suitability on the
      heating system and handling properties. Methods: The present study determines and
      compares data from proximate analysis, calorific values, physical and mechanical
      properties of wood pellets produced from the common tropical species Acacia
      wrightii, Ebenopsis ebano and Havardia pallens. Data were obtained from pellets
      produced from each species chips collected from an experimental plantation and
      analyzed through ANOVA and Kruskal-Wallis test at 0.05 significance level.
      Results: The results of diameter, length and length/diameter ratio didn't show
      statistical differences (p > 0.05) among species. Acacia wrightii showed the
      highest density (1.2 g/cm3). Values on weight retained and compression test
      showed statistical differences (p = 0.05) among species. Havardia pallens was
      more resistant to compression strength than A. wrightii and Ebenopsis ebano.
      Statistical differences (p < 0.01) were also observed for the volatile matter and
      calorific value. E. ebano has the lowest volatile matter (72%), highest calorific
      value (19.6 MJ/kg) as well as the fixed carbon (21%). Discussion: The pellets of
      the species studied have a high energy density, which makes them suitable for
      both commercial and industrial heating applications.A pellet with low compression
      resistance tends to disintegrate easily, due to moisture adsorption. The
      percentages obtained for the resistance index were higher than 97.5%, showing
      that the pellets studied are high-quality biofuels. Proximate analysis values
      also indicate good combustion parameters. Pellets of Acacia wrightii and
      Ebenopsis ebano are the more favorable raw material sources for energy purposes
      because of their high density, calorific value, low ash content and they also met
      majority of the international quality parameters.

PMID- 30202647
TI  - A bioinformatics approach to identifying Wolbachia infections in arthropods.
AB  - Wolbachia is the most widespread endosymbiont, infecting >20% of arthropod
      species, and capable of drastically manipulating the host's reproductive
      mechanisms. Conventionally, diagnosis has relied on PCR amplification; however,
      PCR is not always a reliable diagnostic technique due to primer specificity,
      strain diversity, degree of infection and/or tissue sampled. Here, we look for
      evidence of Wolbachia infection across a wide array of arthropod species using a
      bioinformatic approach to detect the Wolbachia genes ftsZ, wsp, and the groE
      operon in next-generation sequencing samples available through the NCBI Sequence
      Read Archive. For samples showing signs of infection, we attempted to assemble
      entire Wolbachia genomes, and in order to better understand the relationships
      between hosts and symbionts, phylogenies were constructed using the assembled
      gene sequences. Out of the 34 species with positively identified infections,
      eight species of arthropod had not previously been recorded to harbor Wolbachia
      infection. All putative infections cluster with known representative strains
      belonging to supergroup A or B, which are known to only infect arthropods. This
      study presents an efficient bioinformatic approach for post-sequencing diagnosis
      and analysis of Wolbachia infection in arthropods.

PMID- 30202650
TI  - Single mutations in the epsilon subunit from thermophilic Bacillus PS3 generate a
      high binding affinity site for ATP.
AB  - The epsilon subunit from ATP synthases acts as an ATP sensor in the bacterial
      cell to prevent ATP hydrolysis and thus the waste of ATP under conditions of low
      ATP concentration. However, the ATP binding affinities from various bacterial
      organisms differ markedly, over several orders of magnitude. For example, the ATP
      synthases from thermophilic Bacillus PS3 and Escherichia coli exhibit affinities
      of 4 uM and 22 mM, respectively. The recently reported R103A/R115A double mutant
      of Bacillus PS3 ATP synthase demonstrated an increased binding affinity by two
      orders of magnitude with respect to the wild type. Here, we used atomic
      resolution molecular dynamics simulations to determine the role of the R103A and
      R115A single mutations. These lead us to predict that both single mutations also
      cause an increased ATP binding affinity. Evolutionary analysis reveals R103 and
      R115 substitutions in the epsilon subunit from other bacillic organisms, leading
      us to predict they likely have a higher ATP binding affinity than previously
      expected.

PMID- 30202651
TI  - Factors influencing exotic species richness in Argentina's national parks.
AB  - Exotic species introductions are a global phenomenon and protected areas are
      susceptible to them. Understanding the drivers of exotic species richness is
      vital for prioritizing natural resource management, particularly in developing
      countries with limited resources. We analyzed the influence of coarse resolution
      factors on exotic species richness (plants, mammals, and birds) in Argentina's
      National Parks System. We collected data on native species richness, year of park
      formation, park area, region, elevation range, number of rivers crossing area
      boundaries, roads entering area, mean annual rainfall, mean annual temperature,
      mean annual number of visitors, and Human Influence Index within and surrounding
      each park. We compiled 1,688 exotic records in 36 protected areas: 83% plants and
      17% animals (9.5% mammals, 5.5% birds, 1.5% fishes, 0% amphibians, 0% reptiles).
      The five parks with the most exotic species (all taxa combined) were in north
      Patagonia. Exotic grasses were the most common exotic plants, and within animals,
      lagomorphs and feral ungulates were remarkably widespread. Exotic plant richness
      was mostly influenced by temperature and native plant richness, while exotic
      mammal and bird richness was driven mostly by anthropogenic variables, with
      models explaining 36-45% of data deviance. Most variables that positively
      influenced exotic taxa were indirectly related to an increase in spatial
      heterogeneity (natural or anthropogenic), suggesting greater niche space
      variability as facilitators of exotic richness increase. Additional data are
      needed to further investigate the patterns and mechanisms of exotic species
      richness in protected areas, which will help to prioritize the greatest needs of
      monitoring and management.

PMID- 30202653
TI  - Development of a Chlamydomonas reinhardtii metabolic network dynamic model to
      describe distinct phenotypes occurring at different CO2 levels.
AB  - The increase in atmospheric CO2 due to anthropogenic activities is generating
      climate change, which has resulted in a subsequent rise in global temperatures
      with severe environmental impacts. Biological mitigation has been considered as
      an alternative for environmental remediation and reduction of greenhouse gases in
      the atmosphere. In fact, the use of easily adapted photosynthetic organisms able
      to fix CO2 with low-cost operation is revealing its high potential for industry.
      Among those organism, the algae Chlamydomonas reinhardtii have gain special
      attention as a model organism for studying CO2 fixation, biomass accumulation and
      bioenergy production upon exposure to several environmental conditions. In the
      present study, we studied the Chlamydomonas response to different CO2 levels by
      comparing metabolomics and transcriptomics data with the predicted results from
      our new-improved genomic-scale metabolic model. For this, we used in silico
      methods at steady dynamic state varying the levels of CO2. Our main goal was to
      improve our capacity for predicting metabolic routes involved in biomass
      accumulation. The improved genomic-scale metabolic model presented in this study
      was shown to be phenotypically accurate, predictive, and a significant
      improvement over previously reported models. Our model consists of 3726 reactions
      and 2436 metabolites, and lacks any thermodynamically infeasible cycles. It was
      shown to be highly sensitive to environmental changes under both steady-state and
      dynamic conditions. As additional constraints, our dynamic model involved kinetic
      parameters associated with substrate consumption at different growth conditions
      (i.e., low CO2-heterotrophic and high CO2-mixotrophic). Our results suggest that
      cells growing at high CO2 (i.e., photoautotrophic and mixotrophic conditions)
      have an increased capability for biomass production. In addition, we have
      observed that ATP production also seems to be an important limiting factor for
      growth under the conditions tested. Our experimental data (metabolomics and
      transcriptomics) and the results predicted by our model clearly suggest a
      differential behavior between low CO2-heterotrophic and high CO2-mixotrophic
      growth conditions. The data presented in the current study contributes to better
      dissect the biological response of C. reinhardtii, as a dynamic entity, to
      environmental and genetic changes. These findings are of great interest given the
      biotechnological potential of this microalga for CO2 fixation, biomass
      accumulation, and bioenergy production.

PMID- 30202652
TI  - GDF11 induces differentiation and apoptosis and inhibits migration of C17.2
      neural stem cells via modulating MAPK signaling pathway.
AB  - GDF11, a member of TGF-beta superfamily, has recently received widespread
      attention as a novel anti-ageing/rejuvenation factor to reverse age-related
      dysfunctions in heart and skeletal muscle, and to induce angiogenesis and
      neurogenesis. However, these positive effects of GDF11 were challenged by several
      other studies. Furthermore, the mechanism is still not well understood. In the
      present study, we evaluated the effects of GDF11 on C17.2 neural stem cells.
      GDF11 induced differentiation and apoptosis, and suppressed migration of C17.2
      neural stem cells. In addition, GDF11 slightly increased cell viability after 24
      h treatment, showed no effects on proliferation for about 10 days of cultivation,
      and slightly decreased cumulative population doubling for long-term treatment (p
      < 0.05). Phospho-proteome profiling array displayed that GDF11 significantly
      increased the phosphorylation of 13 serine/threonine kinases (p < 0.01),
      including p-p38, p-ERK and p-Akt, in C17.2 cells, which implied the activation of
      MAPK pathway. Western blot validated that the results of phospho-proteome
      profiling array were reliable. Based on functional analysis, we demonstrated that
      the differentially expressed proteins were mainly involved in signal transduction
      which was implicated in cellular behavior. Collectively, our findings suggest
      that, for neurogenesis, GDF11 might not be the desired rejuvenation factor, but a
      potential target for pharmacological blockade.

PMID- 30202654
TI  - Antithrombin deficiency is associated with mortality and impaired organ function
      in septic pediatric patients: a retrospective study.
AB  - Background: Sepsis remains a major problem in intensive care medicine. It is
      often accompanied by coagulopathies, leading to thrombotic occlusion of small
      vessels with subsequent organ damage and even fatal multi-organ failure.
      Prediction of the clinical course and outcome-especially in the heterogeneous
      group of pediatric patients-is difficult. Antithrombin, as an endogenous
      anticoagulant enzyme with anti-inflammatory properties, plays a central role in
      controling coagulation and infections. We investigated the relationship between
      antithrombin levels and organ failure as well as mortality in pediatric patients
      with sepsis. Methods: Data from 164 patients under the age of 18, diagnosed with
      sepsis, were retrospectively reviewed. Antithrombin levels were recorded three
      days before to three days after peak C-reactive protein to correlate antithrombin
      levels with inflammatory activity. Using the concept of developmental
      haemostasis, patients were divided into groups <1 yr and >=1 yr of age. Results:
      In both age groups, survivors had significantly higher levels of antithrombin
      than did deceased patients. An optimal threshold level for antithrombin was
      calculated by ROC analysis for survival: 41.5% (<1 yr) and 67.5% (>=1 yr). The
      mortality rate above this level was 3.3% (<1 yr) and 9.5% (>=1 yr), and below
      this level 41.7% (<1 yr) and 32.2% (>=1 yr); OR 18.8 (1.74 to 1005.02), p =
      0.0047, and OR 4.46 (1.54 to 14.89), p = 0.003. In children <1 yr with
      antithrombin levels <41.5% the rate of respiratory failure (66.7%) was
      significantly higher than in patients with antithrombin levels above this
      threshold level (23.3%), OR 6.23 (1.23 to 37.81), p = 0.0132. In children >=1 yr,
      both liver failure (20.3% vs 1.6%, OR 15.55 (2.16 to 685.01), p = 0.0008) and a
      dysfunctional intestinal tract (16.9% vs 4.8%, OR 4.04 (0.97 to 24.08), p =
      0.0395) occurred more frequently above the antithrombin threshold level of 67.5%.
      Conclusion: In pediatric septic patients, significantly increased mortality and
      levels of organ failure were found below an age-dependent antithrombin threshold
      level. Antithrombin could be useful as a prognostic marker for survival and
      occurrence of organ failure in pediatric sepsis.

PMID- 30202655
TI  - Translational effects of robot-mediated therapy in subacute stroke patients: an
      experimental evaluation of upper limb motor recovery.
AB  - Robot-mediated therapies enhance the recovery of post-stroke patients with motor
      deficits. Repetitive and repeatable exercises are essential for rehabilitation
      following brain damage or other disorders that impact the central nervous system,
      as plasticity permits to reorganize its neural structure, fostering motor
      relearning. Despite the fact that so many studies claim the validity of robot
      mediated therapy in post-stroke patient rehabilitation, it is still difficult to
      assess to what extent its adoption improves the efficacy of traditional therapy
      in daily life, and also because most of the studies involved planar robots. In
      this paper, we report the effects of a 20-session-rehabilitation project
      involving the Armeo Power robot, an assistive exoskeleton to perform 3D upper
      limb movements, in addition to conventional rehabilitation therapy, on 10
      subacute stroke survivors. Patients were evaluated through clinical scales and a
      kinematic assessment of the upper limbs, both pre- and post-treatment. A set of
      indices based on the patients' 3D kinematic data, gathered from an optoelectronic
      system, was calculated. Statistical analysis showed a remarkable difference in
      most parameters between pre- and post-treatment. Significant correlations between
      the kinematic parameters and clinical scales were found. Our findings suggest
      that 3D robot-mediated rehabilitation, in addition to conventional therapy, could
      represent an effective means for the recovery of upper limb disability. Kinematic
      assessment may represent a valid tool for objectively evaluating the efficacy of
      the rehabilitation treatment.

PMID- 30202656
TI  - Impacts of climate change on infestations of Dubas bug (Ommatissus lybicus
      Bergevin) on date palms in Oman.
AB  - Climate change has determined shifts in distributions of species and is likely to
      affect species in the future. Our study aimed to (i) demonstrate the linkage
      between spatial climatic variability and the current and historical Dubas bug
      (Ommatissus lybicus Bergevin) distribution in Oman and (ii) model areas becoming
      highly suitable for the pest in the future. The Dubas bug is a pest of date palm
      trees that can reduce the crop yield by 50% under future climate scenarios in
      Oman. Projections were made in three species distribution models; generalized
      linear model, maximum entropy, boosted regression tree using of four global
      circulation models (GCMs) (a) HadGEM2, (b) CCSM4, (c) MIROC5 and (d) HadGEM2-AO,
      under four representative concentration pathways (2.6, 4.5, 6.0 and 8.5) for the
      years 2050 and 2070. We utilized the most commonly used threshold of maximum
      sensitivity + specificity for classifying outputs. Results indicated that
      northern Oman is currently at great risk of Dubas bug infestations (highly
      suitable climatically) and the infestations level will remain high in 2050 and
      2070. Other non-climatic integrated pest management methods may be greater value
      than climatic parameters for monitoring infestation levels, and may provide more
      effective strategies to manage Dubas bug infestations in Oman. This would ensure
      the continuing competitiveness of Oman in the global date fruit market and
      preserve national yields.

PMID- 30202657
TI  - Lysmata arvoredensis nov. sp. a new species of shrimp from the south coast of
      Brazil with a key to species of Lysmata (Caridea: Lysmatidae) recorded in the
      southwestern Atlantic.
AB  - Lysmata arvoredensis sp. nov. inhabits temperate waters in the south coast of
      Brazil and is named in tribute to the Marine Protected Area REBIO Arvoredo. This
      is the fourth species belonging to the genus Lysmata recorded for the region and
      the ninth for Brazil. L. arvoredensis sp. nov. can be distinguished from other
      species of Lysmata by the presence of a nearly completely fused accessory branch
      with a single free unguiform segment on the outer antennular flagellum; a rostrum
      with seven dorsal (2+5) and three ventral teeth; a stylocerite with a pointed tip
      bearing mesial setae; a second pereiopod with 22-24 carpal subsegments and 14-16
      subsegments in the merus; a merus of the third pereiopod with five ventrolateral
      and 12 ventral spines on the propodus; and its color pattern, with red bands and
      patches in pleonites 2-3 that resemble a mask in dorsal view. Molecular
      characters demonstrate that L. arvoredensis sp. nov. is most closely related to
      other species of Lysmata belonging to the Neotropical and Cleaner clades. To
      support future ecological studies in the region, identification keys to the
      species of Lysmata recorded in the southwestern Atlantic Ocean are provided.

PMID- 30202659
TI  - Estimating the frequency of multiplets in single-cell RNA sequencing from cell
      mixing experiments.
AB  - In single-cell RNA-sequencing, it is important to know the frequency at which the
      sequenced transcriptomes actually derive from multiple cells. A common method to
      estimate this multiplet frequency is to mix two different types of cells (e.g.,
      human and mouse), and then determine how often the transcriptomes contain
      transcripts from both cell types. When the two cell types are mixed in equal
      proportion, the calculation of the multiplet frequency from the frequency of
      mixed transcriptomes is straightforward. But surprisingly, there are no published
      descriptions of how to calculate the multiplet frequency in the general case when
      the cell types are mixed unequally. Here, I derive equations to analytically
      calculate the multiplet frequency from the numbers of observed pure and mixed
      transcriptomes when two cell types are mixed in arbitrary proportions, under the
      assumption that the loading of cells into droplets or wells is Poisson.

PMID- 30202658
TI  - Early Holocene morphological variation in hunter-gatherer hands and feet.
AB  - Background: The Windover mortuary pond dates to the Early Archaic period (6,800
      5,200 years ago) and constitutes one of the earliest archaeological sites with
      intact and well-preserved human remains in North America. Unlike many prehistoric
      egalitarian hunter-gatherers, the Windover people may not have practiced a sex
      based division of labor; rather, they may have shared the load. We explore how
      mobility and subsistence, as reconstructed from archaeological data, influenced
      hand and foot bone morphology at Windover. Methods: We took length and width
      measurements on four carpal bones, four tarsal bones, and load-bearing tarsal
      areas (calcaneus load arm, trochlea of the talus). We analyzed lateralization
      using side differences in raw length and width measurements. For other hypothesis
      testing, we used log transformed length-width ratios to mitigate the confounding
      effects of sexual dimorphism and trait size variation; we tested between-sex
      differences in weight-bearing (rear foot) and shock-absorbing (mid foot) tarsal
      bones and between-sex differences in carpal bones. Results: We identified no
      significant between-sex differences in rear and midfoot areas, suggesting similar
      biomechanical stresses. We identified no significant between-sex differences in
      carpal bones but the test was under-powered due to small sample sizes. Finally,
      despite widespread behavioral evidence on contemporary populations for human hand
      and foot lateralization, we found no evidence of either handedness or footedness.
      Discussion: The lack evidence for footedness was expected due its minimal impact
      on walking gait but the lack of evidence for handedness was surprising given that
      ethnographic studies have shown strong handedness in hunter-gatherers during tool
      and goods manufacture. The reconstructed activity patterns suggested both sexes
      engaged in heavy load carrying and a shared division of labor. Our results
      support previous findings-both sexes had stronger weight-bearing bones. Male
      shock-absorbing bones exhibited a trend towards greater relative width
      (suggesting greater comparative biomechanical stress) than females which may
      reflect the typical pattern of male hunter-gatherers engaging in walking greater
      distances at higher speeds than females. While there were no significant between
      sex differences in carpal bones (supporting a shared work load model), females
      exhibited greater variation in index values, which may reflect a greater variety
      of and specialization in tasks compared to males. Because carpals and tarsals are
      so well-preserved at archaeological sites, we had surmised they might be useful
      proxies for activity in the absence of well-preserved long bones. Tarsals provide
      a stronger signal of past activity and may be useful in the absence of, or in
      addition to, preferred bones. Carpals, however, may not be useful as the effect
      size of biomechanical stress (in this study at least) is low and would require
      larger samples than may be possible at archaeological sites.

PMID- 30202660
TI  - Cell-wall-degrading enzymes produced in vitro and in vivo by Rhizoctonia solani,
      the causative fungus of peanut sheath blight.
AB  - Rhizoctonia solani causes the disease peanut sheath blight, involving symptoms of
      maceration and necrosis of infected tissue, mainly caused by cell-wall-degrading
      enzymes (CWDEs). This study investigated the production of CWDEs including
      polygalacturonase (PG), polymethyl-galacturonase (PMG), cellulase (Cx) and beta
      glucosidase by R. solani in vitro (in liquid culture) and in vivo (in peanut
      plants). Significant PG, PMG, Cx and beta-glucosidase activities were detected in
      infected tissues including stalk and leaves of Baisha and Silihong peanut
      cultivars. Extracts of healthy tissue showed little or no such activities. In
      shaken liquid cultures of R. solani in medium containing pectin or pectin plus
      carboxymethyl cellulose (CMC) as the carbon source(s), PG and PMG were notably
      active. Significant Cx activity was detected in cultures with CMC or pectin plus
      CMC as the carbon source(s). However, only a very low level of beta-glucosidase
      activity was observed in cultures with any of the tested carbon sources. An
      increase of pH was recorded in decayed peanut tissues and liquid culture
      filtrates; the filtrate pH and fungal growth positively correlated. The fungal
      growth and/or pH were important factors for the production of PG, PMG and Cx in
      culture with pectin plus CMC as the carbon source. A single active PG isozyme
      with isoelectric point around 9.2 was detected in culture filtrates and in
      infected peanut tissues by the method of isoelectric focusing electrophoresis.
      The crude enzymes extracted from liquid culture of R. solani induced decay of
      healthy peanut leaves.

PMID- 30202661
TI  - An LED-based multi-actinic illumination system for the high throughput study of
      photosynthetic light responses.
AB  - The responses of photosynthetic organisms to light stress are of interest for
      both fundamental and applied research. Functional traits related to the
      photoinhibition, the light-induced loss of photosynthetic efficiency, are
      particularly interesting as this process is a key limiting factor of
      photosynthetic productivity in algae and plants. The quantitative
      characterization of light responses is often time-consuming and calls for cost
      effective high throughput approaches that enable the fast screening of multiple
      samples. Here we present a novel illumination system based on the concept of
      'multi-actinic imaging' of in vivo chlorophyll fluorescence. The system is based
      on the combination of an array of individually addressable low power RGBW LEDs
      and custom-designed well plates, allowing for the independent illumination of 64
      samples through the digital manipulation of both exposure duration and light
      intensity. The illumination system is inexpensive and easily fabricated, based on
      open source electronics, off-the-shelf components, and 3D-printed parts, and is
      optimized for imaging of chlorophyll fluorescence. The high-throughput potential
      of the system is illustrated by assessing the functional diversity in light
      responses of marine macroalgal species, through the fast and simultaneous
      determination of kinetic parameters characterizing the response to light stress
      of multiple samples. Although the presented illumination system was primarily
      designed for the measurement of phenotypic traits related to photosynthetic
      activity and photoinhibition, it can be potentially used for a number of
      alternative applications, including the measurement of chloroplast phototaxis and
      action spectra, or as the basis for microphotobioreactors.

PMID- 30202662
TI  - Effect of vineyard soil variability on chlorophyll fluorescence, yield and
      quality of table grape as influenced by soil moisture, grown under double
      cropping system in protected condition.
AB  - Environmental factors greatly influence grape quality. Among them, the effect of
      within-vineyard variability of soil in relation to soil moisture on table grape
      under protected condition has rarely been studied. In this present research, we
      investigated the influence of soil variability, in relation with soil moisture on
      chlorophyll fluorescence, yield and quality attributes of the "Summer Black"
      (Vitis vinifera L. * V. labruscana L.) table grape, popularly grown under double
      cropping system in protected covering in the southern part of China. The vineyard
      was divided vertically into three sites (lower, middle and upper, 192, 202 and
      212 m above sea level, respectively) and data on soil moisture and other yield
      and quality parameters were recorded. Among the three vineyard sites, middle site
      resulted in higher yield compared to the upper and lower sites during winter and
      summer cropping cycles. However, compared to regular summer cycle, winter cycle
      provided grapevines with higher quality attributes. Polyphasic OJIP fluorescence
      transient exhibited a considerable increase in fluorescence intensity at J, I and
      P phase in the upper and middle sites compared to the lower site due to variation
      in soil moisture in both seasons. Values of fluorescence parameters including
      minimal fluorescence, relative variable fluorescence at phase J and I, the
      maximal quantum yield of photosystem II were also influenced by soil moisture in
      different sites. Different sites also exhibited a significant difference in total
      phenolics, flavonoid, antioxidant activity and individual anthocyanin which was
      influenced by available soil moisture. The present study shows that chlorophyll
      fluorescence OJIP transient can be used as a sensitive indicator to determine the
      moisture stress in grape grown in a varied soil. Double cropping proved to be a
      powerful technique to improve the fruit quality. This result may be useful for
      the table grape growers to better utilize the vineyard soil variability with
      water management to get higher yield and quality table grape under protected
      condition.

PMID- 30202663
TI  - The first Caipirasuchus (Mesoeucrocodylia, Notosuchia) from the Late Cretaceous
      of Minas Gerais, Brazil: new insights on sphagesaurid anatomy and taxonomy.
AB  - Field work conducted by the staff of the Centro de Pesquisas Paleontologicas
      Llewellyn Ivor Price of the Universidade Federal do Triangulo Mineiro since 2009
      at Campina Verde municipality (MG) have resulted in the discovery of a diverse
      vertebrate fauna from the Adamantina Formation (Bauru Basin). The baurusuchid
      Campinasuchus dinizi was described in 2011 from Fazenda Tres Antas site and after
      that, preliminary descriptions of a partial crocodyliform egg, abelisaurid teeth,
      and fish remains have been done. Recently, the fossil sample has been
      considerably increased including the discovery of several, partially articulated
      fish remains referred to Lepisosteiformes and an almost complete and articulated
      skeleton referred to a new species of Caipirasuchus (Notosuchia, Sphagesauridae),
      which is the main subject of this contribution. At present, this genus was
      restricted to the Adamantina Formation cropping out in Sao Paulo state, with the
      species Caipirasuchus montealtensis, Caipirasuchus paulistanus, and Caipirasuchus
      stenognathus. The new material represents the holotype of a new species,
      Caipirasuchus mineirus n. sp., diferenciated from the previously ones due to the
      following traits: last two maxillary teeth located posterior to anterior edge of
      infraorbital fenestra, elongated lateroventral maxillo-jugal suture-about 1/2 the
      anteroposterior maxillar length-and contact between posterior crest of quadrate
      and posterior end of squamosal forming an almost 90 degrees  flaring roof of the
      squamosal, among others. C. mineirus was found in the same outcrop than
      Campinasuchus but stratigraphically the former occurs in the lower portion of the
      section with no unambiguous data supporting the coexistance of both taxa.

PMID- 30202665
TI  - A Case Report of an Enlarged Suboccipital Nerve with Cutaneous Branch.
AB  - Variations of the suboccipital nerve are infrequently reported. This nerve
      derived from the C1 spinal nerve is usually a small branch that primarily
      innervates the short suboccipital muscles. During the routine dissection of the
      occipital region in an adult cadaver, a vastly enlarged left-sided suboccipital
      nerve was identified. The nerve innervated the short suboccipital muscles and
      overlying semispinalis capitis in normal fashion. However, it continued cranially
      to end in the overlying skin of the occiput. Although not normally thought to
      have a cutaneous branch, recalcitrant occipital neuralgia might be due to such a
      variant branch. Future studies are necessary to further elucidate this proposed
      pathomechanism.

PMID- 30202664
TI  - Spilled Gallstones Silent for a Decade: A Case Report and Review of Literature.
AB  - Laparoscopic cholecystectomy is associated with complications such as gallbladder
      perforation and spillage of gallstones. While these shortcomings are common, the
      occurrence of the resultant nuisances, such as intra-abdominal abscesses, is
      infrequent. We present the case of an individual who developed an intra-abdominal
      abscess following a spillage of gallstones, which occurred after a laparoscopic
      cholecystectomy that was performed more than a decade ago. Herein, we also
      discuss the findings of a literature review that highlights the clinical
      presentations of an intra-abdominal abscess formed due to gallstone spillage
      after a decade of the laparoscopic intervention. We also discuss the underlying
      pathophysiology leading to abscess formation, the imaging modalities used to
      visualize the abscess, as well as the therapeutic strategy used to treat this
      rare clinical entity.

PMID- 30202666
TI  - Risk Factors for Readmission Following Revision Total Hip Arthroplasty in
      Patients Undergoing Surgery for Noninfective Causes.
AB  - Introduction Readmission following revision orthopedic surgery imposes tremendous
      costs due to the increased length of stay, procedure complexity, and revision
      surgery. Following revision total hip arthroplasty, as many as one in five
      patients are readmitted postoperatively. Readmissions cost the federal government
      $17.4 billion annually. The purpose of this study was to identify risk factors
      for unplanned readmission following revision total hip arthroplasty. Methods This
      was a retrospective case series review of randomized revision total hip
      arthroplasties (THA) patients between 2008 and 2018. Exclusions were as follows:
      outside hospital revisions, staged revisions, revisions for infection, and
      bilateral revisions. Data were collected by manual chart review. Readmissions
      were tracked from discharge until the final follow-up. Results A total of 61
      patients and 85 revision THAs were analyzed. Nineteen patients (31.1%) were
      readmitted; 31.6% of the readmitted patients had a coronary artery disease
      compared to 6.5% of non-readmitted patients. Readmission was also associated with
      obesity, former smokers, and hypertension. Also, the mean duration of follow-up
      was 26.5 months for readmitted patients as compared to 8.96 for non-readmitted
      patients. Conclusion Obesity, former tobacco use, younger age, coronary artery
      disease (CAD), and hypertension were associated with readmission. The medical
      optimization of patients with these risk factors prior to surgery could
      significantly lower costs relative to revision THA.

PMID- 30202667
TI  - Comparison of Lichtenstein Repair and Mesh Plug Repair Methods in The Treatment
      of Indirect Inguinal Hernia.
AB  - OBJECTIVE: The lifetime risk to develop an inguinal hernia is 27%-43% for men and
      3%-6% for women. Methods of hernia repair currently involve prosthetic mesh
      applications. The aim of this study is to compare the Lichtenstein repair and
      Mesh-plug repair methods in the surgical treatment of indirect inguinal hernias
      and to identify which of these two techniques is superior regarding its conferred
      advantages. MATERIALS AND METHODS: In this study, a total of 102 patients who
      were diagnosed with indirect inguinal hernia between the years 2014 and 2015
      without a previous operation were analyzed. Patients undergoing Lichtenstein
      repair and Mesh-plug repair were compared, especially during operation time,
      hospital stay, postoperative pain and other aspects. RESULTS: The mean age of
      patients was 28.7 years (19-73). The mean duration of operations and
      hospitalizations was significantly shorter in patients who had undergone mesh
      plug repair. Inguinal pain in the operation area on postoperative day one, two
      weeks and six months was significantly less in patients who had undergone mesh
      plug repair. Patients were followed-up for two years. CONCLUSION: We concluded
      that mesh-plug repair was superior to Lichtenstein repair regarding postoperative
      pain, quality of life of the patient, shorter duration of operation, and duration
      of hospital stay although the two methods were similar regarding both recurrence
      and complication rates. Considering this information, we suggest that mesh-plug
      repair can be used safely for the treatment of indirect inguinal hernias.

PMID- 30202669
TI  - A Sub-acute Cerebral Contusion Presenting with Medication-resistant Psychosis.
AB  - The most common symptoms of a cerebral contusion include headache, dizziness,
      concentration problems, and memory loss. Insomnia is reported by more than half
      of the patients and can exacerbate symptoms. A 24-year-old previously healthy
      male presented with psychosis, acute personality changes, auditory and visual
      hallucinations three weeks after falling 15 feet with concurrent head trauma. A
      right-sided cerebral contusion with concussion was diagnosed on initial admission
      with increasing homicidal and suicidal ideations after 26 hours of insomnia. The
      patient accomplished rest after seven days of medication-resistant insomnia with
      the final combination of ziprasidone and lorazepam. After one night of sleep, the
      patient was alert and oriented with normal mood, affect, and cognition. The
      insomnia appeared to exacerbate this patient's symptoms, and an atypical insomnia
      treatment regimen was required to induce somnolence and restore function in this
      patient. The combination of this abnormal patient presentation along with the
      unorthodox medication regimen makes this case unique compared to other traumatic
      brain injury symptoms and treatments.

PMID- 30202668
TI  - Contribution of Scanopelvimetry in the Prognosis of Childbirth.
AB  - Objectives To determine the frequency of the demand of radiopelvimetry in
      pregnant women and to assess the obstetrical prognosis. Methods Retrospective
      study about 19 months, including a total of 45 pregnant women who underwent
      scanopelvimetry to evaluate the biometry of the pelvis. Scanopelvimetry was
      performed from 36th week of pregnancy. Results The average age of the patients
      was 26.9 years. The frequency of the demand of scanopelvimetry was 0.97%. The
      height of the patients was greater than 150 cm in 84.44%. The indications of
      radiopelvimetry were dominated by the clinical suspicion of pelvic narrowing
      (57.78%), followed by the cephalopelvic confrontation (33.33%) and the
      cicatricial uterus (8.89%). Narrowed pelvis was observed in 28.89% of cases
      (13/45), with a Magnin index of less than 21. A caesarean section during labor
      was performed in 24.44% of the cases. No death of newborn was reported.
      Conclusion The frequency of the demand of scanopelvimetry is low but the rate of
      surgical pelvis is high among suspect cases.

PMID- 30202670
TI  - Shining a Light on Overnight Education: Hospitalist and Resident Impressions of
      the Current State, Barriers, and Methods for Improvement.
AB  - INTRODUCTION: Restrictions on resident work hours and increased requirements for
      resident supervision have led to night float rotations overseen by overnight
      hospitalists (nocturnists). The educational value of night float rotations for
      residents has traditionally been low and studies have yet to elucidate the
      optimal role of nocturnists in resident education. METHODS: We performed a cross
      sectional survey of all residents within our training program and attending
      hospitalists in the department of medicine at our three teaching medical centers.
      Questions sought to investigate the current state of overnight education within
      an internal medicine residency program, understand barriers to overnight
      education, and define best practices for nighttime teaching. RESULTS: Both
      attending and resident physicians reported low satisfaction with the current
      state of overnight education, while simultaneously expressing high levels of
      interest in performing and receiving dedicated nighttime teaching. Attending and
      resident physicians identified similar barriers to overnight teaching (clinical
      work, time coordination, provider fatigue) and agreed on the ideal format for
      overnight didactics (case-based, chalk-talk, 20-minute duration between 10 pm to
      2 am). CONCLUSION: Our study identifies a desire by both faculty and trainees for
      increased overnight teaching and offers a simple initial framework for programs
      to improve overnight housestaff education utilizing nocturnist providers.

PMID- 30202671
TI  - Parkinsonism in a Patient with Human T-lymphotropic Virus 1 Myelopathy.
AB  - Human T-lymphotropic virus 1 (HTLV-1) infection is commonly associated with
      neurological conditions like chronic progressive myelopathy and tropical spastic
      paraparesis (TSP) but rarely also reported with polymyositis, multiple sclerosis,
      and parkinsonism. It is important to recognize that HTLV-1 infection increases
      the risk of these neurological conditions. We present a case of 71-year-old
      female with HTLV-1 associated chronic progressive myelopathy with parkinsonism
      which signifies that it is under-recognized and not frequently reported due to
      lack of expert neurological assessment in these chronically debilitated patients.

PMID- 30202673
TI  - A Rare Cause of Chest Pain.
AB  - Foreign body ingestion occurs mostly among children and mentally impaired adults.
      We present a case of an esophageal foreign body in a mentally healthy adult
      presenting with chest pain. The early recognition and treatment of a sharp,
      pointed foreign body are imperative for appropriate treatment, which can prevent
      possible complications. The esophageal foreign body should be considered a
      possible cause of non-cardiac chest pain in the emergency department.

PMID- 30202672
TI  - Breast Cancer During Pregnancy.
AB  - Breast cancer remains the most common cancer in women. A diagnosis of cancer
      during pregnancy is uncommon. In recent decades, obstetricians are seeing an
      increasing number of women who become pregnant or desire to become pregnant after
      breast cancer treatment because of a delay in childbearing for a variety of
      reasons, including cultural, educational, and professional. Consequently, breast
      cancer in young women often occurs before the completion of reproductive plans. A
      discussion among the patient, the oncologist, and the obstetrician on the
      relative benefits of early delivery followed by treatment versus commencement of
      therapy while continuing the pregnancy is of utmost importance in order to reach
      a consensual decision. The best available evidence suggests that pregnancy after
      breast cancer increases the risk of recurrence. The birth outcome in women with a
      history of breast cancer is no different from that in the normal female
      population; however, increased risks of delivery complications have been reported
      in the literature. As concurrent pregnancy and breast cancer are uncommon, there
      are no data from large randomized trials; hence, recommendations are mainly based
      on retrospective studies.

PMID- 30202674
TI  - Betel Chewing and Nonalcoholic Steatohepatitis.
AB  - Betel chewing is a common social practice in many regions of the world
      particularly in Southeast Asia and among the Asian immigrant populations in the
      West. Several studies have shown betel chewing to be associated with increased
      risk for various health complications including liver cirrhosis and
      hepatocellular carcinoma. The exact mechanism by which betel causes liver damage
      has not been elucidated. We present a 31-year-old Asian immigrant in the United
      States of America (USA) with no family history of the liver disease and non
      smoker who was found to have an unexplained persistent mild elevation of liver
      transaminases. She reported more than 16 kilograms of weight gain over an eight
      year period in association with heavy betel chewing. Despite diet and exercise,
      she was not able to lose weight. Besides, she developed dyslipidemia and gradual
      worsening of glucose tolerance. Liver biopsy showed severe steatosis with
      features of nonalcoholic steatohepatitis (NASH). The gradual development and
      worsening of metabolic syndrome and NASH paralleling betel use are very
      indicative of the hepatic steatosis being caused by betel.

PMID- 30202675
TI  - Results of Nonoperative Treatment for Symptomatic Tarsal Coalitions.
AB  - INTRODUCTION: Recommendations for the initial treatment (nonoperative measures to
      surgical excision) of symptomatic tarsal coalitions vary. Because nonoperative
      outcomes are poorly established, we retrospectively evaluated their success in
      preventing surgery and achieving pain relief for pediatric patients with
      symptomatic tarsal coalitions. MATERIALS AND METHODS:  A retrospective study of
      pediatric patients with symptomatic tarsal coalitions treated at a single
      institution was undertaken. Clinical notes were examined for treatment methods,
      response to treatment, and need for additional procedures. A statistical analysis
      was performed using the chi-square and Mann-Whitney U tests. RESULTS:  Fifty
      symptomatic tarsal coalitions (mean patient age, 11.4 years; range, 8.1-17.9)
      were treated with nonoperative measures. Surgery was not required in 79% of
      calcaneonavicular and 62% of talocalcaneal coalitions. Pain relief was achieved
      in 53% of 81 nonoperative treatment trials. Continuous immobilization via
      casting, intermittent immobilization via walking boot, and supportive measures
      were not significantly different in pain relief (p = 0.35) or preventing surgery
      (p = 0.62). CONCLUSION:  Nonoperative treatment methods have the potential to
      achieve pain relief and prevent or delay surgery for symptomatic tarsal
      coalitions. However, some families may elect to forgo nonoperative measures
      knowing that surgery may eventually be required.

PMID- 30202676
TI  - C-Reactive Protein Monitoring Predicts Neutropenic Fever Following Autologous
      Hematopoietic Stem Cell Transplantation for Multiple Myeloma.
AB  - Background Neutropenic fever (NF) is a known and common complication of
      autologous hematopoietic stem cell transplantation (ASCT). Early risk assessment
      may help direct treatment. We retrospectively analyzed the role of serial serum C
      reactive protein (CRP) levels in predicting NF and assessed the clinical value of
      CRP within 14 days after transplantation. Methods One hundred twenty-one multiple
      myeloma (MM) patients received 170 first and/or second ASCT between January 2014
      and March 2017. A Cox regression model was applied to assess the prognostic value
      of CRP as a time-dependent covariate at the onset of NF within 14 days post
      transplant. Results Forty-seven of 170 patients developed NF. High CRP levels
      (4.0-43.2 mg/dL) were associated with a 5.45-fold increased risk of NF (P =
      0.02). Patients had a nearly three-fold increased risk of NF after the second
      transplant (P < 0.01), but this was not associated with increased mortality.
      Those with NF had higher maximum values of CRP (P < 0.01) which tended to occur
      at or after the onset of NF. Conclusion CRP monitoring provides important
      information about the risk for NF immediately after first MM ASCT, and even more
      so after the second.

PMID- 30202677
TI  - Intermittent Fasting: The Choice for a Healthier Lifestyle.
AB  - Obesity is a worldwide epidemic due to the availability of many unhealthy food
      options and limited physical exercise. Restriction of the daily food intake
      results in weight loss, which is also associated with better health outcomes
      including triglycerides, total cholesterol, low-density lipoprotein cholesterol,
      blood pressure, glucose, insulin, and C-reactive protein. Our aim is to briefly
      discuss the effects of intermittent fasting on weight and other biochemical
      markers mentioned previously. The study is designed as a systematic review
      according to the Preferred Reporting Items for Systematic Reviews and Meta
      Analyses (PRISMA) checklist. To assess the effectiveness of intermittent fasting,
      related studies were reviewed between 2000 and 2018 and 815 studies were
      identified. Only four articles met the preset inclusion and exclusion criteria.
      All four studies have shown a significant decrease in fat mass with P-values
      <0.01. It was also noted that some biochemical markers were significantly reduced
      such as the reduction in low-density lipoprotein and triglyceride with P-values <
      0.05. Other biochemical markers had inconsistent results. Based on the
      qualitative analysis, intermittent fasting was found to be efficient in reducing
      weight, irrespective of the body mass index. Further studies are needed to assess
      the ability to maintain the lost weight without regaining it and the long-term
      effects of such dietary changes.

PMID- 30202678
TI  - Pauci-immune Glomerulonephritis in Systemic Lupus Erythematosus (SLE).
AB  - Glomerulonephritis (GN) in lupus is generally an immune complex
      glomerulonephritis from the deposition of immunoglobulin and complements. Pauci
      immune GN is the most common cause of rapidly progressive GN and is frequently
      associated with an anti-nuclear cytoplasmic antibody (ANCA). We report a patient
      with a history of systemic lupus erythematosus who presented with worsening
      proteinuria and was subsequently diagnosed with pauci-immune GN on renal biopsy,
      in the absence of ANCA.

PMID- 30202679
TI  - Impact of Storage Lesion on Post-transfusion Rise in Hemoglobin.
AB  - BACKGROUND: The storage lesion is defined as the set of changes that occur in red
      blood cells (RBCs) during storage. Studies have shown that a prolonged storage
      period of RBCs is associated with increased destruction after transfusion. The
      aim of this study is to determine the impact of the storage lesion on the
      efficacy of RBC transfusions by comparing the mean rise in the hemoglobin of
      patients who received new vs old blood. METHODS: We did a retrospective chart
      review of all patients who received a single unit of pure red blood cell (PRBC)
      transfusion in a three-month period. Patients with hemolytic anemia and active
      bleeding were excluded. The storage lesion was estimated by calculating the
      number of days to expiration on the day of transfusion. Median days to expiration
      was calculated to be 11 days. Patients were divided into two groups based on days
      to expiration. Group A included patients who received old blood (days to
      expiration: 0-11) and group B included patients who received new blood (days to
      expiration: 11-38). The mean rise in hemoglobin between the two groups was
      compared using the paired t-test. RESULTS: The baseline characteristics of both
      groups were similar. There was no statistically significant difference in the
      mean rise in hemoglobin (1.01 vs 1.08- p-value 0.298), hematocrit (3.37 vs 3.61-
      p-value 0.249), and RBC count (0.42 vs 0.44- p-value 0.097) in the group that
      received old blood vs new blood, respectively. CONCLUSION: An RBC transfusion
      with a shorter storage period does not increase hemoglobin more than RBC with a
      longer storage period.

PMID- 30202680
TI  - The structural and chemical basis of temporary adhesion in the sea star Asterina
      gibbosa.
AB  - Background: Marine biological adhesives are a promising source of inspiration for
      biomedical and industrial applications. Nevertheless, natural adhesives and
      especially temporary adhesion systems are mostly unexplored. Sea stars are able
      to repeatedly attach and detach their hydraulic tube feet. This ability is based
      on a duo-gland system and, upon detachment, the adhesive material stays behind on
      the substrate as a 'footprint'. In recent years, characterization of sea star
      temporary adhesion has been focussed on the forcipulatid species Asterias rubens.
      Results: We investigated the temporary adhesion system in the distantly related
      valvatid species Asterina gibbosa. The morphology of tube feet was described
      using histological sections, transmission-, and scanning electron microscopy.
      Ultrastructural investigations revealed two adhesive gland cell types that both
      form electron-dense secretory granules with a more lucid outer rim and one de
      adhesive gland cell type with homogenous granules. The footprints comprised a
      meshwork on top of a thin layer. This topography was consistently observed using
      various methods like scanning electron microscopy, 3D confocal interference
      microscopy, atomic force microscopy, and light microscopy with crystal violet
      staining. Additionally, we tested 24 commercially available lectins and two
      antibodies for their ability to label the adhesive epidermis and footprints. Out
      of 15 lectins labelling structures in the area of the duo-gland adhesive system,
      only one also labelled footprints indicating the presence of glycoconjugates with
      alpha-linked mannose in the secreted material. Conclusion: Despite the distant
      relationship between the two sea star species, the morphology of tube feet and
      topography of footprints in A. gibbosa shared many features with the previously
      described findings in A. rubens. These similarities might be due to the
      adaptation to a benthic life on rocky intertidal areas. Lectin- and immuno
      labelling indicated similarities but also some differences in adhesive
      composition between the two species. Further research on the temporary adhesive
      of A. gibbosa will allow the identification of conserved motifs in sea star
      adhesion and might facilitate the development of biomimetic, reversible glues.

PMID- 30202681
TI  - A scanning probe microscopy study of nanostructured TiO2/poly(3-hexylthiophene)
      hybrid heterojunctions for photovoltaic applications.
AB  - The nanoscale morphology of photoactive hybrid heterojunctions plays a key role
      in the performances of hybrid solar cells. In this work, the heterojunctions
      consist of a nanocolumnar TiO2 surface covalently grafted with a monolayer of
      poly(3-hexylthiophene) (P3HT) functionalized with carboxylic groups (-COOH).
      Through a joint analysis of the photovoltaic properties at the nanoscale by
      photoconductive-AFM (PC-AFM) and surface photovoltage imaging, we investigated
      the physical mechanisms taking place locally during the photovoltaic process and
      the correlation to the nanoscale morphology. A down-shift of the vacuum level of
      the TiO2 surface upon grafting was measured by Kelvin probe force microscopy
      (KPFM), evidencing the formation of a dipole at the TiO2/P3HT-COOH interface.
      Upon in situ illumination, a positive photovoltage was observed as a result of
      the accumulation of photogenerated holes in the P3HT layer. A positive
      photocurrent was recorded in PC-AFM measurements, whose spatial mapping was
      interpreted consistently with the corresponding KPFM analysis, offering a
      correlated analysis of interest from both a theoretical and material design
      perspective.

PMID- 30202682
TI  - Localized photodeposition of catalysts using nanophotonic resonances in silicon
      photocathodes.
AB  - Nanostructured semiconductors feature resonant optical modes that confine light
      absorption in specific areas called "hot spots". These areas can be used for
      localized extraction of the photogenerated charges, which in turn could drive
      chemical reactions for synthesis of catalytic materials. In this work, we use
      these nanophotonic hot spots in vertical silicon nanowires to locally deposit
      platinum nanoparticles in a photo-electrochemical system. The tapering angle of
      the silicon nanowires as well as the excitation wavelength are used to control
      the location of the hot spots together with the deposition sites of the platinum
      catalyst. A combination of finite difference time domain (FDTD) simulations with
      scanning electron microscopy image analysis showed a reasonable correlation
      between the simulated hot spots and the actual experimental localization and
      quantity of platinum atoms. This nanophotonic approach of driving chemical
      reactions at the nanoscale using the optical properties of the photo-electrode,
      can be very promising for the design of lithography-free and efficient
      hierarchical nanostructures for the generation of solar fuels.

PMID- 30202683
TI  - Phosphorus monolayer doping (MLD) of silicon on insulator (SOI) substrates.
AB  - This paper details the application of phosphorus monolayer doping of silicon on
      insulator substrates. There have been no previous publications dedicated to the
      topic of MLD on SOI, which allows for the impact of reduced substrate dimensions
      to be probed. The doping was done through functionalization of the substrates
      with chemically bound allyldiphenylphosphine dopant molecules. Following
      functionalization, the samples were capped and annealed to enable the diffusion
      of dopant atoms into the substrate and their activation. Electrical and material
      characterisation was carried out to determine the impact of MLD on surface
      quality and activation results produced by the process. MLD has proven to be
      highly applicable to SOI substrates producing doping levels in excess of 1 * 1019
      cm-3 with minimal impact on surface quality. Hall effect data proved that
      reducing SOI dimensions from 66 to 13 nm lead to an increase in carrier
      concentration values due to the reduced volume available to the dopant for
      diffusion. Dopant trapping was found at both Si-SiO2 interfaces and will be
      problematic when attempting to reach doping levels achieved by rival techniques.

PMID- 30202684
TI  - Spin-coated planar Sb2S3 hybrid solar cells approaching 5% efficiency.
AB  - Antimony sulfide solar cells have demonstrated an efficiency exceeding 7% when
      assembled in an extremely thin absorber configuration deposited via chemical bath
      deposition. More recently, less complex, planar geometries were obtained from
      simple spin-coating approaches, but the device efficiency still lags behind. We
      compare two processing routes based on different precursors reported in the
      literature. By studying the film morphology, sub-bandgap absorption and solar
      cell performance, improved annealing procedures are found and the crystallization
      temperature is shown to be critical. In order to determine the optimized
      processing conditions, the role of the polymeric hole transport material is
      discussed. The efficiency of our best solar cells exceeds previous reports for
      each processing route, and our champion device displays one of the highest
      efficiencies reported for planar antimony sulfide solar cells.

PMID- 30202685
TI  - Light-Matter interactions on the nanoscale.

PMID- 30202686
TI  - Electrospun one-dimensional nanostructures: a new horizon for gas sensing
      materials.
AB  - Electrospun one-dimensional (1D) nanostructures are rapidly emerging as key
      enabling components in gas sensing due to their unique electrical, optical,
      magnetic, thermal, mechanical and chemical properties. 1D nanostructures have
      found applications in numerous areas, including healthcare, energy storage,
      biotechnology, environmental monitoring, and defence/security. Their enhanced
      specific surface area, superior mechanical properties, nanoporosity and improved
      surface characteristics (in particular, uniformity and stability) have made them
      important active materials for gas sensing applications. Such highly sensitive
      and selective elements can be embedded in sensor nodes for internet-of-things
      applications or in mobile systems for continuous monitoring of air pollutants and
      greenhouse gases as well as for monitoring the well-being and health in everyday
      life. Herein, we review recent developments of gas sensors based on electrospun
      1D nanostructures in different sensing platforms, including optical,
      conductometric and acoustic resonators. After explaining the principle of
      electrospinning, we classify sensors based on the type of materials used as an
      active sensing layer, including polymers, metal oxide semiconductors, graphene,
      and their composites or their functionalized forms. The material properties of
      these electrospun fibers and their sensing performance toward different analytes
      are explained in detail and correlated to the benefits and limitations for every
      approach.

PMID- 30202687
TI  - Interaction-induced zero-energy pinning and quantum dot formation in Majorana
      nanowires.
AB  - Majorana modes emerge in non-trivial topological phases at the edges of specific
      materials such as proximitized semiconducting nanowires under an external
      magnetic field. Ideally, they are non-local states that are charge-neutral
      superpositions of electrons and holes. However, in nanowires of realistic length
      their wave functions overlap and acquire a finite charge that makes them
      susceptible to interactions, specifically with the image charges that arise in
      the electrostatic environment. Considering a realistic three-dimensional model of
      the dielectric surroundings, here we show that, under certain circumstances,
      these interactions lead to a suppression of the Majorana oscillations predicted
      by simpler theoretical models, and to the formation of low-energy quantum-dot
      states that interact with the Majorana modes. Both features are observed in
      recent experiments on the detection of Majoranas and could thus help to properly
      characterize them.

PMID- 30202688
TI  - Filling nanopipettes with apertures smaller than 50 nm: dynamic
      microdistillation.
AB  - Using nanopipettes with very small apertures (<10 nm) is a good way to improve
      the spatial resolution in scanning conductance experiments, to monitor single
      molecule delivery and to strain long molecules stretching during translocation.
      However, such nanopipettes can be difficult to fill. Here we describe a dynamic
      microdistillation technique that successfully fills all nanopipettes, whatever
      their shape or tip radius. Even elongated or bent nanopipettes with a small-angle
      tip are completely filled using this new technique. The nanopipettes are first
      filled with pure water, which is later replaced with the desired electrolyte via
      electromigration. Electrical measurements are used to check that filling is
      complete.

PMID- 30202689
TI  - Dumbbell gold nanoparticle dimer antennas with advanced optical properties.
AB  - Plasmonic nanoantennas have found broad applications in the fields of
      photovoltaics, electroluminescence, non-linear optics and for plasmon enhanced
      spectroscopy and microscopy. Of particular interest are fundamental limitations
      beyond the dipolar approximation limit. We introduce asymmetric gold nanoparticle
      antennas (AuNPs) with improved optical near-field properties based on the
      formation of sub-nanometer size gaps, which are suitable for studying matter with
      high-resolution and single molecule sensitivity. These dumbbell antennas are
      characterized in regard to their far-field and near-field properties and are
      compared to similar dimer and trimer antennas with larger gap sizes. The
      tailoring of the gap size down to sub-nanometer length scales is based on the
      integration of rigid macrocyclic cucurbituril molecules. Stable dimer antennas
      are formed with an improved ratio of the electromagnetic field enhancement and
      confinement. This ratio, taken as a measure of the performance of an antenna, can
      even exceed that exhibited by trimer AuNP antennas composed of comparable
      building blocks with larger gap sizes. Fluctuations in the far-field and near
      field properties are observed, which are likely caused by distinct deviations of
      the gap geometry arising from the faceted structure of the applied colloidal
      AuNPs.

PMID- 30202690
TI  - Influence of the thickness of an antiferromagnetic IrMn layer on the static and
      dynamic magnetization of weakly coupled CoFeB/IrMn/CoFeB trilayers.
AB  - The static and dynamic magnetization response of the CoFeB/IrMn/CoFeB trilayer
      system with varying thickness of the antiferromagnetic (AF) IrMn layer is
      investigated using magnetization hysteresis (M-H) and ferromagnetic resonance
      (FMR) measurements. The study shows that the two CoFeB layers are coupled via a
      long-range dynamic exchange effect through the IrMn layer up to a thickness of 6
      nm. It is found that with the increase in IrMn layer thickness a nearly linear
      enhancement of the effective magnetic damping constant occurs, which is
      associated with the simultaneous influence of spin pumping and interlayer
      exchange coupling effects. An extrinsic contribution to the linewidth originating
      from the two-magnon scattering is also discussed. The AF-induced interfacial
      damping parameter is derived by studying the evolution of damping with inverse
      CoFeB thickness. The static magnetic measurements also reveal the interlayer
      exchange coupling across the IrMn layer both at room temperature and low
      temperature. The asymmetric hysteresis loop and training effect observed at low
      temperature is related to the presence of a metastable AF domain state. We show
      that both the static and dynamic magnetic properties of trilayer films can be
      adjusted over a wide range by changing the thickness of the IrMn spacer layer.

PMID- 30202692
TI  - The role of adatoms in chloride-activated colloidal silver nanoparticles for
      surface-enhanced Raman scattering enhancement.
AB  - Chloride-capped silver nanoparticles (Cl-AgNPs) allow for high-intensity surface
      enhanced Raman scattering (SERS) spectra of cationic molecules to be obtained
      (even at nanomolar concentration) and may also play a key role in understanding
      some fundamental principles behind SERS. In this study, we describe a fast (<10
      min) and simple protocol for obtaining highly SERS-active colloidal silver
      nanoparticles (AgNPs) with a mean diameter of 36 nm by photoconversion from AgCl
      precursor microparticles in the absence of any organic reducing or capping agent.
      The resulting AgNPs are already SERS-activated by the Cl- ions chemisorbed onto
      the metal surface where the chloride concentration in the colloidal solution is
      10-2 M. Consequently, the enhanced SERS spectra of cationic dyes (e.g., crystal
      violet or 9-aminoacridine) demonstrate the advantages of Cl-AgNPs compared to the
      as-synthesized AgNPs obtained by standard Ag+ reduction with hydroxylamine (hya
      AgNPS) or citrate (cit-AgNPs). The results of SERS experiments on anionic and
      cationic test molecules comparing Cl-AgNPs, hya-AgNPs and cit-AgNPs colloids
      activated with different amounts of Cl- and/or cations such as Ag+, Mg2+ or Ca2+
      can be explained within the understanding of the adatom model - the chemisorption
      of cationic analytes onto the metal surface is mediated by the Cl- ions, whereas
      ions like Ag+, Mg2+ or Ca2+ mediate the electronic coupling of anionic species to
      the silver metal surface. Moreover, the SERS effect is switched on only after the
      electronic coupling of the adsorbate to the silver surface at SERS-active sites.
      The experiments presented in this study highlight the SERS-activating role played
      by ions such as Cl-, Ag+, Mg2+ or Ca2+, which is a process that seems to prevail
      over the Raman enhancement due to nanoparticle aggregation.

PMID- 30202693
TI  - Optimization of the optical coupling in nanowire-based integrated photonic
      platforms by FDTD simulation.
AB  - The optimized design of a photonic platform based on a nanowire light emitting
      diode (LED) and a nanowire photodetector connected with a waveguide is proposed.
      The light coupling efficiency from the LED to the detector is optimized as a
      function of the geometrical parameters of the system using the finite difference
      time domain simulation tool Lumerical. Starting from a design reported in the
      literature with a coupling efficiency of only 8.7%, we propose an optimized
      photonic platform with efficiency reaching 65.5%.

PMID- 30202691
TI  - Lead-free hybrid perovskites for photovoltaics.
AB  - This review covers the state-of-the-art in organo-inorganic lead-free hybrid
      perovskites (HPs) and applications of these exciting materials as light
      harvesters in photovoltaic systems. Special emphasis is placed on the influence
      of the spatial organization of HP materials both on the micro- and nanometer
      scale on the performance and stability of perovskite-based solar light
      converters. This review also discusses HP materials produced by isovalent
      lead(II) substitution with Sn2+ and other metal(II) ions, perovskite materials
      formed on the basis of M3+ cations (Sb3+, Bi3+) as well as on combinations of
      M+/M3+ ions aliovalent to 2Pb2+ (Ag+/Bi3+, Ag+/Sb3+, etc.). The survey is
      concluded with an outlook highlighting the most promising strategies for future
      progress of photovoltaic systems based on lead-free perovskite compounds.

PMID- 30202694
TI  - Intrinsic ultrasmall nanoscale silicon turns n-/p-type with SiO2/Si3N4-coating.
AB  - Impurity doping of ultrasmall nanoscale (usn) silicon (Si) currently used in
      ultralarge scale integration (ULSI) faces serious miniaturization challenges
      below the 14 nm technology node such as dopant out-diffusion and inactivation by
      clustering in Si-based field-effect transistors (FETs). Moreover, self
      purification and massively increased ionization energy cause doping to fail for
      Si nano-crystals (NCs) showing quantum confinement. To introduce electron- (n-)
      or hole- (p-) type conductivity, usn-Si may not require doping, but an energy
      shift of electronic states with respect to the vacuum energy between different
      regions of usn-Si. We show in theory and experiment that usn-Si can experience a
      considerable energy offset of electronic states by embedding it in silicon
      dioxide (SiO2) or silicon nitride (Si3N4), whereby a few monolayers (MLs) of SiO2
      or Si3N4 are enough to achieve these offsets. Our findings present an alternative
      to conventional impurity doping for ULSI, provide new opportunities for ultralow
      power electronics and open a whole new vista on the introduction of p- and n-type
      conductivity into usn-Si.

PMID- 30202695
TI  - Surface energy of nanoparticles - influence of particle size and structure.
AB  - The surface energy, particularly for nanoparticles, is one of the most important
      quantities in understanding the thermodynamics of particles. Therefore, it is
      astonishing that there is still great uncertainty about its value. The
      uncertainty increases if one questions its dependence on particle size. Different
      approaches, such as classical thermodynamics calculations, molecular dynamics
      simulations, and ab initio calculations, exist to predict this quantity.
      Generally, considerations based on classical thermodynamics lead to the
      prediction of decreasing values of the surface energy with decreasing particle
      size. This phenomenon is caused by the reduced number of next neighbors of
      surface atoms with decreasing particle size, a phenomenon that is partly
      compensated by the reduction of the binding energy between the atoms with
      decreasing particle size. Furthermore, this compensating effect may be expected
      by the formation of a disordered or quasi-liquid layer at the surface. The
      atomistic approach, based either on molecular dynamics simulations or ab initio
      calculations, generally leads to values with an opposite tendency. However, it is
      shown that this result is based on an insufficient definition of the particle
      size. A more realistic definition of the particle size is possible only by a
      detailed analysis of the electronic structure obtained from initio calculations.
      Except for minor variations caused by changes in the structure, only a minor
      dependence of the surface energy on the particle size is found. The main
      conclusion of this work is that surface energy values for the equivalent bulk
      materials should be used if detailed data for nanoparticles are not available.

PMID- 30202696
TI  - Nanoscale characterization of the temporary adhesive of the sea urchin
      Paracentrotus lividus.
AB  - Background: Unlike the thin homogeneous films that are typical for adhesives
      produced by humans, biological adhesives present complex hierarchical micro- and
      nanostructures. Most studies on marine adhesives have focused on permanent
      adhesives, whereas the nanostructures of nonpermanent, temporary or reversible
      adhesives have only been examined in some organisms such as marine flatworms,
      barnacle cyprids, freshwater cnidaria and echinoderms such as sea cucumbers and
      sea stars. In this study, the first nanoscale characterization of sea urchin
      temporary adhesives was performed using atomic force microscopy (AFM). Results:
      The adhesive topography was similar under dry and native (seawater) conditions,
      which was comprised of a honeycomb-like meshwork of aggregated globular
      nanostructures. In terms of adhesion forces, higher values were obtained in dry
      conditions, reaching up to 50 nN. Under native conditions, lower adhesive forces
      were obtained (up to 500 pN) but the adhesive seemed to behave like a functional
      amyloid, as evidenced by the recorded characteristic sawtooth force-extension
      curves and positive thioflavin-T labelling. Conclusion: Our results confirm that
      like other temporary adhesives, the sea urchin adhesive footprint nanostructure
      consists of a meshwork of entangled globular nanostructures. Under native
      conditions, the adhesive footprints of the sea urchin behaved like a functional
      amyloid, suggesting that among its proteinaceous constituents there are most
      likely proteins with amyloid quaternary structures or rich in beta-sheets. These
      results extend our knowledge on sea urchin adhesive composition and mechanical
      properties essential for the engineering of biomimetic adhesives.

PMID- 30202697
TI  - Two-dimensional photonic crystals increasing vertical light emission from Si
      nanocrystal-rich thin layers.
AB  - We have fabricated two-dimensional photonic crystals (PhCs) on the surface of Si
      nanocrystal-rich SiO2 layers with the goal to maximize the photoluminescence
      extraction efficiency in the normal direction. The fabricated periodic structures
      consist of columns ordered into square and hexagonal pattern with lattice
      constants computed such that the red photoluminescence of Si nanocrystals (SiNCs)
      could couple to leaky modes of the PhCs and could be efficiently extracted to
      surrounding air. Samples having different lattice constants and heights of
      columns were investigated in order to find the configuration with the best
      performance. Spectral overlap of the leaky modes with the luminescence spectrum
      of SiNCs was verified experimentally by measuring photonic band diagrams of the
      leaky modes employing angle-resolved spectroscopy and also theoretically by
      computing the reflectance spectra. The extraction enhancement within different
      spatial angles was evaluated by means of micro-photoluminescence spectroscopy.
      More than 18-fold extraction enhancement was achieved for light propagating in
      the normal direction and up to 22% increase in overall intensity was obtained at
      the spatial collection angle of 14 degrees .

PMID- 30202700
TI  - Performance analysis of rigorous coupled-wave analysis and its integration in a
      coupled modeling approach for optical simulation of complete heterojunction
      silicon solar cells.
AB  - A variety of light management structures have been introduced in solar cells to
      improve light harvesting and further boost their conversion efficiency. Reliable
      and accurate simulation tools are required to design and optimize the individual
      structures and complete devices. In the first part of this paper, we analyze the
      performance of rigorous coupled-wave analysis (RCWA) for accurate three
      dimensional optical simulation of solar cells, in particular heterojunction
      silicon (HJ Si) solar cells. The structure of HJ Si solar cells consists of thin
      and thick layers, and additionally, micro- and nano-textures are also introduced
      to further exploit the potential of light trapping. The RCWA was tested on the
      front substructure of the solar cell, including the texture, thin passivation and
      contact layers. Inverted pyramidal textures of different sizes were included in
      the simulations. The simulations rapidly converge as long as the textures are
      small (in the (sub)micrometer range), while for larger microscale textures
      (feature sizes of a few micrometers), this is not the case. Small textures were
      optimized to decrease the reflectance, and consequently, increase the absorption
      in the active layers of the solar cell. Decreasing the flat parts of the texture
      was shown to improve performance. For simulations of structures with
      microtextures, and for simulations of complete HJ Si cells, we propose a coupled
      modeling approach (CMA), where the RCWA is coupled with raytracing and the
      transfer matrix method. By means of CMA and nanotexture optimization, we show the
      possible benefits of nanotextures at the front interface of HJ Si solar cells,
      demonstrating a 13.4% improvement in the short-circuit current density with
      respect to the flat cell and 1.4% with respect to the cell with double-sided
      random micropyramids. We additionally demonstrate the ability to simulate a
      combination of nano- and microtextures at a single interface, although the
      considered structure did not show an improvement over the pyramidal textures.

PMID- 30202698
TI  - Hierarchical heterostructures of Bi2MoO6 microflowers decorated with Ag2CO3
      nanoparticles for efficient visible-light-driven photocatalytic removal of toxic
      pollutants.
AB  - Developing highly active and durable visible-light-driven photocatalysts for the
      degradation of toxic pollutants is of vital significance. Herein, Ag2CO3
      nanoparticles were in situ formed on Bi2MoO6 microflowers to produce
      Ag2CO3/Bi2MoO6 heterostructures via a facile procedure. The morphologies, phases,
      chemical compositions, and optical properties of Ag2CO3/Bi2MoO6 were examined by
      multiple characterization techniques. The Ag2CO3/Bi2MoO6 heterostructures
      exhibited substantially improved performance in the removal of industrial dyes
      (rhodamine B (RhB), methyl orange (MO), and methyl blue (MB)), and the antibiotic
      tetracycline hydrochloride (TC), compared with bare Bi2MoO6 and Ag2CO3 under
      visible-light irradiation. The enhancement of activity was attributed to the high
      charge-separation capacity, which results from the matched band alignment of the
      two components. The cycling experiments showed a good durability of
      Ag2CO3/Bi2MoO6. Holes were found to be the dominant active species accounting for
      the pollutant degradation. This compound is a promising candidate for wastewater
      treatment.

PMID- 30202699
TI  - Metal-dielectric hybrid nanoantennas for efficient frequency conversion at the
      anapole mode.
AB  - Background: Dielectric nanoantennas have recently emerged as an alternative
      solution to plasmonics for nonlinear light manipulation at the nanoscale, thanks
      to the magnetic and electric resonances, the strong nonlinearities, and the low
      ohmic losses characterizing high refractive-index materials in the visible/near
      infrared (NIR) region of the spectrum. In this frame, AlGaAs nanoantennas
      demonstrated to be extremely efficient sources of second harmonic radiation. In
      particular, the nonlinear polarization of an optical system pumped at the anapole
      mode can be potentially boosted, due to both the strong dip in the scattering
      spectrum and the near-field enhancement, which are characteristic of this mode.
      Plasmonic nanostructures, on the other hand, remain the most promising solution
      to achieve strong local field confinement, especially in the NIR, where metals
      such as gold display relatively low losses. Results: We present a nonlinear
      hybrid antenna based on an AlGaAs nanopillar surrounded by a gold ring, which
      merges in a single platform the strong field confinement typically produced by
      plasmonic antennas with the high nonlinearity and low loss characteristics of
      dielectric nanoantennas. This platform allows enhancing the coupling of light to
      the nanopillar at coincidence with the anapole mode, hence boosting both second-
      and third-harmonic generation conversion efficiencies. More than one order of
      magnitude enhancement factors are measured for both processes with respect to the
      isolated structure. Conclusion: The present results reveal the possibility to
      achieve tuneable metamixers and higher resolution in nonlinear sensing and
      spectroscopy, by means of improved both pump coupling and emission efficiency due
      to the excitation of the anapole mode enhanced by the plasmonic nanoantenna.

PMID- 30202701
TI  - Nanotribology.

PMID- 30202702
TI  - Block copolymers for designing nanostructured porous coatings.
AB  - Highly ordered porous coatings find applications in many fields, such as
      nanotechnology, microfluidics and nanofluidics, membrane separation, and sensing.
      In recent years, there has been great interest regarding the synthesis of
      isoporous and well-ordered (in)organic coatings for the production of highly
      selective functional membranes. Among the different strategies that have been
      proposed to date for preparing these porous thin coatings, one simple route
      involves the use of self-assembled amphiphilic block copolymers either as the
      porogen (acting as sacrificial templating agents for the production of inorganic
      architectures) or as a source of the porogen (by self-assembly for the production
      of polymeric substrates). Therefore, an extended discussion around the
      exploitation of block copolymers is proposed here in this review, using
      polystyrene-block-polyethylene oxide (PS-b-PEO) as the model substrate, and
      critical points are highlighted.

PMID- 30202703
TI  - Magnetism and magnetoresistance of single Ni-Cu alloy nanowires.
AB  - Arrays of magnetic Ni-Cu alloy nanowires with different compositions were
      prepared by a template-replication technique using electrochemical deposition
      into polycarbonate nanoporous membranes. Photolithography was employed for
      obtaining interdigitated metallic electrode systems of Ti/Au onto SiO2/Si
      substrates and subsequent electron beam lithography was used for contacting
      single nanowires in order to investigate their galvano-magnetic properties. The
      results of the magnetoresistance measurements made on single Ni-Cu alloy
      nanowires of different compositions have been reported and discussed in detail. A
      direct methodology for transforming the magnetoresistance data into the
      corresponding magnetic hysteresis loops was proposed, opening new possibilities
      for an easy magnetic investigation of single magnetic nanowires in the peculiar
      cases of Stoner-Wohlfarth-like magnetization reversal mechanisms. The magnetic
      parameters of single Ni-Cu nanowires of different Ni content have been estimated
      and discussed by the interpretation of the as derived magnetic hysteresis loops
      via micromagnetic modeling. It has been theoretically proven that the proposed
      methodology can be applied over a large range of nanowire diameters if the
      measurement geometry is suitably chosen.

PMID- 30202704
TI  - Pinning of a ferroelectric Bloch wall at a paraelectric layer.
AB  - The phase-field simulations of ferroelectric Bloch domain walls in BaTiO3-SrTiO3
      crystalline superlattices performed in this study suggest that a paraelectric
      layer with a thickness comparable to the thickness of the domain wall itself can
      act as an efficient pinning layer. At the same time, such a layer facilitates the
      possibility to switch domain wall helicity by an external electric field or even
      to completely change the characteristic structure of a ferroelectric Bloch wall
      passing through it. Thus, ferroelectric Bloch domain walls are shown to be ideal
      nanoscale objects with switchable properties. The reported results hint towards
      the possibility to exploit ferroelectric domain wall interaction with simple
      nanoscale devices.

PMID- 30202706
TI  - Editorial.

PMID- 30202705
TI  - Electronic and Geometric Structures of Paramagnetic Diazadiene Complexes of
      Lithium and Sodium.
AB  - The electronic and molecular structures of the lithium and sodium complexes of
      1,4-bis(2,6-diisopropylphenyl)-2,3-dimethyl-1,4-diazabutadiene (Me2DADDipp) were
      fully characterized by using a multi-frequency electron paramagnetic resonance
      (EPR) spectroscopy approach and crystallography, together with density functional
      theory (DFT) calculations. EPR measurements, using T1 relaxation-time-filtered
      pulse EPR spectroscopy, revealed the diagonal elements of the A and g tensors for
      the metal and ligand sites. It was found that the central metals in the lithium
      complexes had sizable contributions to the SOMO, whereas this contribution was
      less strongly observed for the sodium complex. Such strong contributions were
      attributed to structural specifications (e.g. geometrical data and atomic size)
      rather than electronic effects.

PMID- 30202707
TI  - Obstructive Sleep Apnea in Elective Spine Surgery: National Prevalence and
      Inpatient Outcomes.
AB  - Study Design: Retrospective cohort study. Objectives: Epidemiologic studies
      suggest that the prevalence of moderate to severe obstructive sleep apnea (OSA)
      is increasing. OSA has been linked to increased rates of postoperative
      complications following surgery. Large studies, however, regarding surgical
      outcomes in this patient population, particularly in the spine literature, are
      limited. Consequently, the purpose of this study was to assess the prevalence of
      and postoperative risks conferred by OSA in the elective spine population.
      Methods: Using data from the National Inpatient Sample from 2008 to 2012, an
      estimated 56 372 (5.1%) patients with OSA undergoing elective cervical and
      thoracolumbar spine surgery were selected and compared to 1 052 837 patients
      without OSA undergoing the same procedures. Our primary outcome measures included
      postoperative complication rates, inpatient mortality, length of stay, and total
      hospital charges. Results: Patients with OSA were, on average 2.6 years older
      than those without OSA (P < .001) and had a higher comorbidity burden. The
      prevalence of OSA increased between 2008 and 2012 from 3.5% to 6.8%; P < .001.
      OSA was associated with a 3-fold increase in major complications (P < .001) and
      was confirmed as an independent risk factor for major complications based on
      multivariate analysis (odds ratio [OR] = 2.82; 95% CI = 2.59-2.79; P < .001).
      Rates of deep venous thrombosis were doubled in patients with OSA. OSA was
      determined to be an independent predictor of pulmonary complications (OR = 2.69;
      95% CI = 2.59-2.79; P < .001). OSA did not increase the risk of postoperative
      mortality. Conclusions: Patients with OSA often have multiple concomitant
      comorbidities and consequently are at increased risk of experiencing a more
      difficult postoperative course following elective spine surgery. Specifically,
      increased risks of pulmonary complications and deep venous thrombosis should be
      anticipated.

PMID- 30202708
TI  - The Effectiveness of Bioskills Training for Simulated Lumbar Pedicle Screw
      Placement.
AB  - Study Design: Prospective randomized study. Objectives: To define the impact of
      an inexpensive, user-friendly, and reproducible lumbar pedicle screw
      instrumentation bioskills training module and evaluation protocol. Methods:
      Participants were randomized to control (n = 9) or intervention (n = 10) groups
      controlling for level of experience (medical students, junior resident, or senior
      resident). The intervention group underwent a 20-minute bioskills training module
      while the control group spent the same time with self-directed study. Pre- and
      posttest performance was self-reported (Physician Performance Diagnostic
      Inventory Scale [PPDIS]). Objective outcome scores were obtained from a blinded
      fellowship-trained attending orthopedic spine surgeon using Objective Structured
      Assessment of Technical Skills (OSATS) and Objective Pedicle Instrumentation
      Score metrics. In addition, identification of pedicle breach and breach anatomic
      location was measured pre- and posttest in lumbar spine models. Results: The
      intervention group showed a 30.8% improvement in PPDIS scores, compared with
      13.4% for the control group (P = .01). The intervention group demonstrated
      statistically significant 66% decrease in breaches (P = .001) compared with 28%
      decrease in the control group (P = .06). Breach identification demonstrated no
      change in accuracy of the control group (incorrect identification from 32.2% pre-
      to posttest 35%; P = .71), whereas the intervention group's improvement was
      statistically significant (42% pre- to posttest 36.5%; P = .0047). Conclusions:
      We conclude that a concise lumbar pedicle screw instrumentation bioskills
      training session can be a useful educational tool to augment clinical education.

PMID- 30202709
TI  - Incidence of Osteoporosis-Related Complications Following Posterior Lumbar
      Fusion.
AB  - Study Design: Retrospective review. Objectives: This study investigates the
      prevalence of adverse postsurgical events, or osteoporosis-related complications
      (ORCs), following spinal fusion. Methods: Patients undergoing primary posterior
      thoracolumbar or lumbar fusion by 1 of 2 surgeons practicing at a single
      institution were analyzed from 2007 to 2014. ORCs were defined in one of the
      following categories: revision surgery, compression fracture, proximal junctional
      kyphosis, pseudarthrosis, or failure of instrumentation. Patients with a bone
      mineral density of the hips and/or spine performed within 1 year of the index
      procedure were included. Patients were stratified into normal bone density,
      osteopenia, and osteoporosis using WHO guidelines. Patients were excluded if they
      were younger than 18 years at the time of surgery, with infection, malignancy,
      skeletal dysplasia, neuromuscular disorders, concomitant or staged anterior
      posterior procedure, or fusion performed because of trauma. Results: Out of 140
      patients included, the prevalence of normal bone density was 31.4% (44/140),
      osteopenia 58.6% (82/140), and osteoporosis 10.0% (14/140). There were no
      differences between groups for gender, age, body mass index, and interbody device
      rate. The overall prevalence of ORCs was 32.1% (45/140). By group, there was a
      prevalence of 22.7% (10/44), 32.9% (27/82), and 50.0% (7/14) for normal bone
      density, osteopenia, and osteoporosis, respectively. These differences were
      significantly higher for both the osteopenia and osteoporosis groups.
      Conclusions: Patients with T scores below -1.0 undergoing posterior lumbar fusion
      have an increased prevalence of ORCs. Consideration of bone density plays a
      crucial role in patient selection, medical management, and counseling patient
      expectations.

PMID- 30202711
TI  - Outcomes After Spine Surgery Among Patients Who Have Had Prior Bariatric Surgery.
AB  - Study Design: Retrospective cohort study. Objectives: We hypothesized that spine
      surgery patients with a history of bariatric surgery do not differ in
      expectations of surgery, perceived benefit of surgical intervention, or physician
      determined outcome of surgery from patients with no history of bariatric surgery.
      Methods: Patients seen in our spine clinic between January 1, 2 009 and December
      30, 2 010 were reviewed. Included patients had a history of bariatric surgery and
      were 18 to 89 years old. We compared their expectations for recovery, self
      perceived clinical outcome (Oswestry Disability Index [ODI] or Neck Disability
      Index [NDI] and visual analog scale [VAS]), satisfaction with surgery, and
      physician-perceived clinical outcome (Odom's criteria) to a matched cohort with
      no such history. Patients were matched by type of surgery (approach, levels, and
      procedure), diagnosis, sex, body mass index (BMI), weight category, age, and
      smoking status. Results: Of 210 included patients, 89 underwent spine surgery.
      One bariatric patient could not be matched. Seventeen received cervical spine
      surgery; 71 received lumbar spine surgery. The 2 cohorts had similar expectations
      and satisfaction. Patients with no history of bariatric surgery tended to be more
      satisfied than the bariatric surgery patients, but not significantly so. ODI/NDI
      and VAS scores were statistically worse for the bariatric cohort. Differences
      were attributed to differences among lumbar spine surgery patients; neck surgery
      patients were not different. Odom's scores were not different between the two.
      Conclusions: Postoperative expectations and satisfaction of bariatric patients
      are similar to those of nonbariatric patients. Bariatric patients receiving
      lumbar spine surgery experienced inferior clinical outcomes compared with
      nonbariatric patients. Cervical spine surgery bariatric patients have similar
      clinical outcomes as nonbariatric patients.

PMID- 30202710
TI  - Finite Element Analysis of Long Posterior Transpedicular Instrumentation for
      Cervicothoracic Fractures Related to Ankylosing Spondylitis.
AB  - Study Design: Biomechanical finite element model analysis. Objectives: Spinal
      fractures related to ankylosing spondylitis (AS) are often treated by long
      posterior stabilization. The objective of this study is to develop a finite
      element model (FEM) for spinal fractures related to AS and to establish a
      biomechanical foundation for long posterior stabilization of cervicothoracic
      fractures related to AS. Methods: An existing FEM (consisting of 2 separately
      developed models) including the cervical and thoracic spine were adapted to the
      conditions of AS (all discs fused, C0-C1 and C1-C2 mobile). A fracture at the
      level C6-C7 was simulated. Besides a normal spine (no AS, no fracture) and the
      uninstrumented fractured spine 4 different posterior transpedicular
      instrumentations were tested. Three loads (1.5g, 3.0g, 4.5g) were applied
      according to a specific load curve. Results: All posterior stabilization methods
      could normalize the axial stability at the fracture site as measured with gap
      distance. The maximum stress at the cranial instrumentation end (C3-C4) was
      slightly greater if every level was instrumented, than in the skipped level
      model. The skipped level instrumentation achieved similar rotatory stability as
      the long multilevel instrumentation. Conclusions: Skipping instrumentation levels
      without giving up instrumentation length reduced stresses in the ossified tissue
      within the range of the instrumentation and did not decrease the stability in a
      FEM of a cervicothoracic fracture related to AS. Considering the risks associated
      with every additional screw placed, the skipped level instrumentation has
      advantages regarding patient safety.

PMID- 30202712
TI  - Fusion Assessment by MRI in Comparison With CT in Anterior Lumbar Interbody
      Fusion: A Prospective Study.
AB  - Study Design: Prospective cohort study. Objectives: To evaluate the role of
      magnetic resonance imaging (MRI) in evaluation of fusion status following
      anterior lumbar interbody fusion (ALIF) and compare agreement and confidence in
      assessing fusion or its absence on MRI to the current standard computed
      tomography (CT). Methods: A prospective follow up of patients undergoing surgery
      by 2 spine surgeons between 2012 and 2015 at a single institution. Fusion was
      assessed at different time points in these patients by 2 independent
      musculoskeletal radiologists. Fusion was analyzed in coronal and sagittal planes
      using both imaging modalities, with confidence being attributed on a scale of 0
      to 3. Assessors were blinded to patient data. Results: Fourteen patients (25
      levels) with mean follow-up of 10.2 months (range 2.4-20.3 years) and age of 41
      years (range 20.7-61.5 years) were assessed. MRI within the interbody cage in
      coronal (kappa = .58) and sagittal (kappa = .50) planes had the highest
      interobserver agreement. CT anterior to the cage in coronal (kappa = .48) and
      sagittal (kappa = .44) planes, as well as within the cage in coronal (kappa =
      .50) and sagittal planes (kappa = .44) showed moderate agreement. Confidence
      anterior to the interbody cage using MRI scan was reduced when compared with
      remaining angles and imaging modalities. Conclusions: The study demonstrates that
      MRI may be a useful tool in the assessment of fusion following ALIF with results
      comparable to CT, and that it may have a useful role in select patients
      especially considering marked radiation exposure reduction.

PMID- 30202713
TI  - Trends in Lumbar Fusion Surgery Among Octogenarians: A Nationwide Inpatient
      Sample Study From 2004 to 2013.
AB  - Study Design: Retrospective analysis. Objectives: Given the aging US population
      and natural degenerative process of the spine, more elderly patients with lumbar
      spinal disease are surgical candidates. Prior studies have assessed safety and
      efficacy of lumbar fusion (LF) surgeries in the elderly, but none have reviewed
      fusion procedures from an epidemiological standpoint. Here, we report 2004-2013
      national trends in demographics, discharge time, and economic impact of LF
      procedures for octogenarians. Methods: The Nationwide Inpatient Sample database
      was queried from 2004 to 2013 for LF procedures in patients aged 80 to 89 years.
      Patients were grouped by fusion level, demographics, comorbidity score,
      insurance, and hospital characteristics. Postoperative variables include length
      of stay and total in-hospital charges. Data was evaluated using chi-squared tests
      and t tests. Results: The national sample included 17 471 LF procedures (mean age
      = 82.65 years). From 2004 to 2013, the annual number of LF procedures increased
      from 1144 to 2061 patients. Percentage of multilevel LF was relatively maintained
      (mean = 18%). The majority of patients were female (mean = 62%). The proportion
      of males increased during the study period (31.8% to 42.5%; P < .0001). The
      proportion of patients with a comorbidity score of 2 or 3 increased during the
      study period (P < .0001). Over time, average length of stay decreased (from 6 to
      4.5 days; P < .0001), and total in-hospital charges increased (from $58 471 to
      $111 235; P < .0001). Conclusions: These results suggest that more lumbar fusion
      procedures are being performed on octogenarians in recent years. While these
      patients are discharged from hospitals more quickly after surgery, there is also
      greater financial burden placed on patients, hospitals, and society.

PMID- 30202714
TI  - Differences in Cross-Sectional Intervertebral Foraminal Area From C3 to C7.
AB  - Study Design: Anatomical comparative study. Objectives: Few studies have
      evaluated foraminal areas in the cervical spine without degenerative changes. The
      purpose of this study was to determine and compare the mean cross-sectional
      foraminal areas between the C3/4, C4/5, C5/6, and C6/7 levels while also
      analyzing specimens for differences between sexes and races. Methods: We
      performed an anatomic study of the intervertebral foramen at 4 levels (C3/4,
      C4/5, C5/6, C6/7) in 100 skeletally mature osseous specimens. Specimens were
      selected to obtain equal number of African American and Caucasian males and
      females (n = 25/group) aged 20 to 40 years at time of death. Foramina were
      photographed bilaterally with and without a silicone rubber disc. The maximal
      vertical height and mid-sagittal width of each foramen were digitally measured
      and the areas were calculated using an ellipse as a model. Results: The average
      age at death for all specimens was 30 +/- 6 years. The mean cross-sectional area
      of the C4/5 foramen was significantly smaller compared with the C5/6 (P < .001).
      C5/6 was significantly narrower than C6/7 (P < .001) foramen with and without
      disc augmentation. C3/4 was not significantly different from more caudal levels.
      There was no difference between male and female specimens, while African
      Americans had smaller foraminal sizes than Caucasians. Conclusions: This study
      provides the largest anatomical reference of the cervical intervertebral foramen.
      In a mature spine without facet joint hypertrophy or osteophytic changes, the
      C4/5 foramen was narrower than C5/6, which was narrower than C6/7. Understanding
      the relative foraminal areas in the nonpathological cervical spine is crucial to
      understanding degenerative changes as well as the anatomical changes in
      pathologies that affect the intervertebral foramen.

PMID- 30202715
TI  - Biomechanics of L5/S1 in Long Thoracolumbosacral Constructs: A Cadaveric Study.
AB  - Study Design: In vitro cadaveric biomechanical study. Objectives: Despite
      numerous techniques employed to establish solid lumbosacral fixation, there are
      little biomechanical data correlating fixation methods at L5/S1 to
      thoracolumbosacral (TLS) construct length. We aimed to determine the optimal
      construct with the hypothesis that under physiological loads, lumbosacral
      constructs can be stabilized by L5/S1 anterior lumbar interbody fusion (ALIF)
      alone, without iliac screw fixation (ISF), and that TLS constructs would require
      ISF, with or without ALIF. Methods: By using a robot capable of motion in 6 axes,
      force-moment sensor, motion-tracking camera system and software, we simulated the
      spinal loading effects in flexion-extension, axial rotation, and lateral bending,
      and compared torques in different construct groups of T4-S1, T10-S1, and L2-S1.
      By conducting multidirectional flexibility testing we assessed the effects of
      constructs of various lengths on the L5/S1 segment. Results: L2-S1 constructs may
      be equivalently stabilized by L5/S1 ALIF alone without ISF. Longer TLS constructs
      exerted increasing motion at L5/S1, exhibiting trends in favor of ISF when
      extending to T10 and statistically improved fixation when extending to T4.
      Lastly, TLS constructs with ISF exhibited a statistically significant reduction
      in L5-S1 range of motion from the addition of ALIF when extending to T4-pelvis
      but not T10-pelvis. Conclusions: We found that ALIF alone may sufficiently
      support the L2-S1 construct, reducing L5/S1 range of motion and transmitting
      loads instead to the sacropelvis. Furthermore, ALIF was found to add significant
      stability to the T4-pelvis construct when added to ISF. This difference was not
      significant for the T10-pelvis construct.

PMID- 30202716
TI  - Diabetes Mellitus as a Risk Factor for Acute Postoperative Complications
      Following Elective Adult Spinal Deformity Surgery.
AB  - Study Design: Retrospective cohort study. Objectives: Diabetes mellitus is a
      highly prevalent disease in the United States. Adult spinal deformity (ASD)
      surgery encompasses a wide variety of spinal disorders and is associated with a
      morbidity rate between 20% and 80%. Considering utilization of spinal surgery
      will continue to increase, this study investigates the influence of diabetes
      mellitus on acute postoperative outcomes following elective ASD surgery. Methods:
      The 2010-2014 American College of Surgeon's National Surgical Quality Improvement
      Program database was queried using Current Procedural Terminology and
      International Classification of Diseases (9th Revision) diagnosis codes relevant
      to ASD surgery. Patients were divided into cohorts based on their diabetic
      status. Bivariate and multivariate logistic regression analyses were employed to
      identify which 30-day postoperative outcomes patients are at risk for. Results: A
      total of 5809 patients met the inclusion criteria for the study of which 4553
      (84.2%) patients were nondiabetic, 578 (10.7%) patients had non-insulin-dependent
      diabetes mellitus (NIDDM), and 275 (5.1%) patients had insulin-dependent diabetes
      mellitus (IDDM). Diabetes status was significantly associated with length of stay
      >=5 days (NIDDM: odds ratio [OR] = 1.27, 95% confidence interval [CI] = 1.02
      1.58, P = .034; IDDM: OR = 1.55, 95% CI = 1.15-2.09, P = .004), any complication
      (NIDDM: OR = 1.26, 95% CI = 1.01-1.58, P = .037), urinary tract infection (NIDDM:
      OR = 1.87, 95% CI = 1.14-3.05, P = .012), and cardiac complications (IDDM: OR =
      4.05, 95% CI = 1.72-9.51, P = .001). Conclusions: Given the prevalence of
      diabetes, surgeons will invariably encounter these patients for ASD surgery. The
      present study identifies the increased risk NIDDM and IDDM patients experience
      following ASD surgery. Quantification of this increased risk may improve the
      selection of appropriate surgical candidates, patient risk stratification, and
      patient postoperative safety.

PMID- 30202717
TI  - The Posterior Use of BMP-2 in Cervical Deformity Surgery Does Not Result in
      Increased Early Complications: A Prospective Multicenter Study.
AB  - Study Design: Prospective cohort study. Objectives: To describe the rate of short
      term complications following the posterior use of recombinant human bone
      morphogenetic protein-2 (rhBMP-2) in cervical deformity (CD) surgery. Methods: CD
      patients from 2013 to 2015 were enrolled in a prospective, multicenter database.
      Patients were divided into those receiving rhBMP-2 (BMP) and no rhBMP-2 (NOBMP).
      The relationship between BMP use, demographic variables surgical variables,
      radiographic parameters and complications was evaluated. Results: A total of 100
      patients (47 BMP, 53 NOBMP) were included. Follow-up time averaged 7.6 months
      (range 3-12 months). An average of 13.6mg of BMP was used per person with 1.49 mg
      per level. Compared with the NOBMP group, patients in the BMP group were older (P
      = .03). BMP was more commonly used in patients that and had longer prior fusions
      (6.0 vs 2.5, P < .01). There were no differences between groups with regards to a
      history of surgery, Charlson Comorbidity Index, estimated blood loss, operation
      time, fusion levels, and surgical approach. The maintenance of radiographic
      parameters at 6-month follow-up was similar. There were no differences in terms
      of total complication incidence, total complications per person, major
      complications per person or any specific complication. Linear regression and
      Pearson correlation analysis did not reveal any strong r2 values (r2 = 0.09,
      0.08, 0.06) between the use of BMP and complications (major or operative).
      Conclusions: BMP use was not directly associated with an increased incidence of
      early complications in this prospective cohort of operative adult CD patients.
      Its use was associated with increased number of levels instrumented and fused.

PMID- 30202720
TI  - Parametric and Nonparametric Tests in Spine Research: Why Do They Matter?

PMID- 30202718
TI  - The Science and Clinical Applications of Placental Tissues in Spine Surgery.
AB  - Study Design: Narrative literature review. Objectives: Placental tissue,
      amniotic/chorionic membrane, and umbilical cord have seen a recent expansion in
      their clinical application in various fields of surgery. It is important for
      practicing surgeons to know the underlying science, especially as it relates to
      spine surgery, to understand the rationale and clinical indication, if any, for
      their usage. Methods: A literature search was performed using PubMed and MEDLINE
      databases to identify studies reporting the application of placental tissues as
      it relates to the practicing spine surgeon. Four areas of interest were
      identified and a comprehensive review was performed of available literature.
      Results: Clinical application of placental tissue holds promise with regard to
      treatment of intervertebral disc pathology, preventing epidural fibrosis, spinal
      dysraphism closure, and spinal cord injury; however, there is an overall paucity
      of high-quality evidence. As such, evidence-based guidelines for its clinical
      application are currently unavailable. Conclusions: There is no high-level
      clinical evidence to support the application of placental tissue for spinal
      surgery, although it does hold promise for several areas of interest for the
      practicing spine surgeon. High-quality research is needed to define the clinical
      effectiveness and indications of placental tissue as it relates to spine surgery.

PMID- 30202719
TI  - The Role of Prognostic Scoring Systems in Assessing Surgical Candidacy for
      Patients With Vertebral Metastasis: A Narrative Review.
AB  - Study Design: Narrative review. Objectives: To review the relevant literature
      regarding scoring systems for vertebral metastases and quantify their role in
      contemporary orthopedic practice. Methods: A literature search of PubMed, Google
      Scholar, and Embase was performed on February 7, 2017. Eight scoring systems were
      selected for detailed review-7 of which were scores focused solely on patient
      prognosis (Tokuhashi, Tomita, Bauer, Oswestry Spinal Risk Index, Van der Linden,
      Rades, and Katagiri). The eighth system reviewed was the Spinal Instability
      Neoplastic Score, which examines for impending spinal instability in patients
      with vertebral metastases and represents a novel approach compared with hitherto
      scoring systems. Results: The Bauer and Oswestry Spinal Risk Index have the most
      accurate prognostic predictive ability, with the newer Oswestry Spinal Risk Index
      being favored by the contemporary literature as it demands less investigation and
      is therefore more readily accessible. There was a growing trend in studies
      designed to customize scoring systems for individual cancer pathological
      subtypes. The Spinal Instability Neoplastic Score shows good reliability for
      predicting instability among surgeons and oncologists. Conclusions: The increased
      understanding of cancer pathology and subsequent development of customized
      treatments has led to prolonged survival. For patients with vertebral metastases,
      this affects surgical candidacy not only on the basis of prognosis but also
      provides prolonged opportunity for the development of spinal instability. Scoring
      systems have a useful guidance role in these deciding for/against surgical
      intervention, but in order to remain contemporary ongoing review, development,
      and revalidation is mandatory.

PMID- 30202721
TI  - The rates of quinolone, trimethoprim/sulfamethoxazole and aminoglycoside
      resistance among Enterobacteriaceae isolated from urinary tract infections in
      Azerbaijan, Iran.
AB  - Aim: Antibiotic susceptibility patterns help to select appropriate empirical
      treatments of urinary tract infections (UTIs). This study aimed to investigate
      antibiotic resistance among Enterobacteriaceae isolated from UTIs in Azerbaijan,
      Iran. Methods: This study was carried out during 2016 in hospitals located in
      Tabriz, Urmia, and Khoy. Midstream urine specimens were cultured and identified
      by the standard methods. Susceptibility testing was carried out using the disk
      diffusion agar method for cefotaxime, ceftazidime, ceftriaxone, cefoxitin,
      imipenem, meropenem, ertapenem, cefepime, ampicillin, cefazolin, cefuroxime,
      aztreonam, nitrofurantoin, and fosfomycin and the agar dilution method for MIC
      determination of aminoglycosides, quinolones, sulfamethoxazole, and trimethoprim.
      Results: A total of 219 non-duplicated Enterobacteriaceae were isolated from
      UTIs. According to the agar dilution assay, the following resistance rates were
      determined: trimethoprim/sulfamethoxazole (co-trimoxazole) 69.8%, nalidixic acid
      68.9%, ciprofloxacin 66.2%, levofloxacin 58.5%, tobramycin 47.9%, kanamycin
      39.3%, gentamicin 27.8%, and amikacin 5.5%. High levels of resistance were
      observed to trimethoprim (78.5%), sulfamethoxazole (88.1%), ampicillin (86.3%),
      and cephazoline (79.4%). Conclusion: The most effective agents against
      Enterobacteriaceae were fosfomycin, carbapenems, and amikacin. Quinolones,
      trimethoprim and sulfamethoxazole are not appropriate for empirical therapy due
      to high levels of resistance. Amikacin is more effective among aminoglycosides
      and may be more effective, in complicated cases, when used in combination with
      fosfomycin and carbapenems.

PMID- 30202722
TI  - Constraints to implementing guidelines for the identification, assessment, and
      management of childhood obesity in the clinical care setting: Prevention and
      treatment framework.
AB  - : The "Pathway for the Identification, Assessment and Management of Overweight
      and Obese Children & Youth" was developed to support healthcare providers in
      identifying and treating childhood obesity in British Columbia (Canada). Purpose:
      The study aimed to determine the feasibility and effectiveness of using the
      Pathway in clinical settings. Methods: 13 healthcare providers (7 family
      physicians, 2 pediatricians, 2 registered dietitians, and 2 nurse practitioners)
      assessed the Pathway and participated in semi-structured interviews in 2015. A
      direct constant comparative analysis guided the coding of the interviews in the
      NVivo 9 software. Results: The interviews uncovered the complexity of factors
      that influenced practices of healthcare providers. Three broad issues were
      identified as required if the "Pathway" were to be used and fully implemented in
      practices. First, the "Pathway" needs to be modified in terms of how it is
      presented and explained and be supplemented with appropriate documentation and
      resources for its implementation, Second, the constraints that limit
      implementation need to be addressed and should include a focus on both individual
      (i.e., the healthcare providers themselves) and environmental (i.e., factors
      within and outside of providers' organizations) factors. Lastly, there is a need
      to establish processes and/or infrastructure for adapting the "Pathway" to the
      local context as resources and supports vary by organizations and regions.
      Conclusion: Healthcare providers should be involved in screening and managing
      childhood obesity. Addressing the challenges found in this study will enable
      healthcare providers to take a more active role in addressing childhood obesity
      in their day to day practices.

PMID- 30202723
TI  - Crouzon syndrome: Genetic and intervention review.
AB  - Crouzon syndrome exhibits considerable phenotypic heterogeneity, in the aetiology
      of which genetics play an important role. FGFR2 mediates extracellular signals
      into cells and the mutations in the FGFR2 gene cause this syndrome occurrence.
      Activated FGFs/FGFR2 signaling disrupts the balance of differentiation, cell
      proliferation, and apoptosis via its downstream signal pathways. However, very
      little is known about the cellular and molecular factors leading to severity of
      this phenotype. Revealing the molecular pathology of craniosynostosis will be a
      great value for genetic counselling, diagnosis, prognosis and early intervention
      programs. This mini-review summarizes the fundamental and recent scientific
      literature on genetic disorder of Crouzon syndrome and presents a graduated
      strategy for the genetic approach, diagnosis and the management of this complex
      craniofacial defect.

PMID- 30202726
TI  - Corrigendum to 'Cave Diving for a Diagnosis: Disseminated Histoplasmosis in the
      Immunocompromised' [IDCases 12 (2018) 92-94].
AB  - [This corrects the article DOI: 10.1016/j.idcr.2018.03.020.].

PMID- 30202727
TI  - Cytomegalovirus infection in immunocompetent adults: Is observation still the
      best strategy?
AB  - Cytomegalovirus (CMV) infection in immunocompetent patients generally resolves
      with few sequelae. However, it can cause severe and relapsing symptoms that can
      last for several weeks. Due to the self-limiting nature of CMV disease in
      immunocompetent individuals, criteria for specific antiviral therapy in this
      cohort are not well established. Additionally the adverse effect profile of
      currently available anti-CMV therapy limits its use in specific patient
      populations .We describe 3 immunocompetent adults who developed symptomatic CMV
      infection and were ill for several weeks. All patients had positive CMV viral
      assays and ultimately received anti-CMV therapy with significant improvement in
      symptoms within a few days of starting therapy. Choosing appropriate candidates
      for anti-CMV therapy, among mmunocompetent individuals, requires further
      research.

PMID- 30202724
TI  - Neurophysiological correlates of Avolition-apathy in schizophrenia: A resting-EEG
      microstates study.
AB  - Background: The "Avolition-apathy" domain of the negative symptoms was found to
      include different symptoms by factor analytic studies on ratings derived by
      different scales. In particular, the relationship of anhedonia with this domain
      is controversial. Recently introduced negative symptom rating scales provide a
      better assessment of anhedonia, allowing the distinction of anticipatory and
      consummatory aspects, which might be related to different psychopathological
      dimensions. The study of associations with external validators, such as
      electrophysiological, brain imaging or cognitive indices, might shed further
      light on the status of anhedonia within the Avolition-apathy domain. Objectives:
      We used brain electrical microstates (MSs), which represent subsecond periods of
      quasi-stable scalp electrical field, associated with resting-state neural
      networks (and thus with global patterns of functional connectivity), to test
      whether the component symptoms of Avolition-apathy share the same correlates.
      Method: We analyzed multichannel resting EEGs in 142 individuals with
      schizophrenia (SCZ) and in 64 healthy controls (HC), recruited within the add-on
      EEG study of the Italian Network for Research on Psychoses. Relative time
      contribution, duration and occurrence of four MS classes (MS-A/-B/-C/-D) were
      calculated. Group differences on MS parameters (contribution and duration) and
      their associations with negative symptom domains (assessed using the Brief
      Negative Symptoms Scale) were investigated. Results: SCZ, in comparison to HC,
      showed increased contribution and duration of MS-C. The contribution of MS-A
      positively correlated with Avolition-apathy, but not with Expressive deficit.
      Within the Avolition-apathy domain, anticipatory anhedonia, avolition and
      asociality, but not consummatory anhedonia, showed the same correlations with MS
      A contribution. Conclusion: Our findings support the existence of distinct
      electrophysiological correlates of Avolition-apathy with respect to Expressive
      deficit, and lend support to the hypothesis that only the anticipatory component
      of anhedonia shares the same pathophysiological underpinnings of the Avolition
      apathy domain.

PMID- 30202728
TI  - Non-malignant CSF lymphocytosis in a patient with acute lymphoblastic leukemia.
AB  - Patients with haematological malignancy are often profoundly immune suppressed,
      and more so if they require more than one line of therapy. Infection should
      always be considered when they become unwell. We discuss the differential
      diagnoses of a young man with multiply-relapsed Philadelphia chromosome-positive
      B-cell acute lymphoblastic leukaemia who presented with neurological symptoms and
      cerebrospinal fluid lymphocytosis. The diagnostic approach needs to be rapid and
      structured, and may require microbiology and neurology support.

PMID- 30202725
TI  - Reduced sound-evoked and resting-state BOLD fMRI connectivity in tinnitus.
AB  - : The exact neurophysiological basis of chronic tinnitus, which affects 10-15% of
      the population, remains unknown and is controversial at many levels. It is an
      open question whether phantom sound perception results from increased central
      neural gain or not, a crucial question for any future therapeutic intervention
      strategies for tinnitus. We performed a comprehensive study of mild hearing
      impaired participants with and without tinnitus, excluding participants with co
      occurrences of hyperacusis. A right-hemisphere correlation between tinnitus
      loudness and auditory perceptual difficulty was observed in the tinnitus group,
      independent of differences in hearing thresholds. This correlation was linked to
      reduced and delayed sound-induced suprathreshold auditory brain responses (ABR
      wave V) in the tinnitus group, suggesting subsided rather than exaggerated
      central neural responsiveness. When anatomically predefined auditory regions of
      interest were analysed for altered sound-evoked BOLD fMRI activity, it became
      evident that subcortical and cortical auditory regions and regions involved in
      sound detection (posterior insula, hippocampus), responded with reduced BOLD
      activity in the tinnitus group, emphasizing reduced, rather than increased,
      central neural gain. Regarding previous findings of evoked BOLD activity being
      linked to positive connectivities at rest, we additionally analysed r-fcMRI
      responses in anatomically predefined auditory regions and regions associated with
      sound detection. A profound reduction in positive interhemispheric connections of
      homologous auditory brain regions and a decline in the positive connectivities
      between lower auditory brainstem regions and regions involved in sound detection
      (hippocampus, posterior insula) were observed in the tinnitus group. The finding
      went hand-in-hand with the emotional (amygdala, anterior insula) and
      temporofrontal/stress-regulating regions (prefrontal cortex, inferior frontal
      gyrus) that were no longer positively connected with auditory cortex regions in
      the tinnitus group but were instead positively connected to lower-level auditory
      brainstem regions. Delayed sound processing, reduced sound-evoked BOLD fMRI
      activity and altered r-fcMRI in the auditory midbrain correlated in the tinnitus
      group and showed right hemisphere dominance as did tinnitus loudness and
      perceptual difficulty. The findings suggest that reduced central neural gain in
      the auditory stream may lead to phantom perception through a failure to energize
      attentional/stress-regulating networks for contextualization of auditory-specific
      information. Reduced auditory-specific information flow in tinnitus has until now
      escaped detection in humans, as low-level auditory brain regions were previously
      omitted from neuroimaging studies. TRIAL REGISTRATION: German Clinical Trials
      Register DRKS0006332.

PMID- 30202729
TI  - A case report and literature review of daptomycin-induced liver injury.
AB  - Daptomycin is a lipopeptide antimicrobial used to treat gram positive organisms
      including multi-drug resistant infections. It has been shown to occasionally
      cause abnormalities in liver function but more commonly is associated with
      elevations in serum creatinine phosphokinase (CK) (Hair and Keam, 2007) [1]. We
      describe a case where a patient being treated for methicillin-resistant
      Staphylococcus aureus (MRSA) bacteremia with daptomycin developed asymptomatic
      elevated transaminases without evidence of multiorgan failure, hyperbilirubinemia
      or elevation of CK levels. Other etiologies for liver injury were considered and
      ruled out, and after daptomycin was discontinued, the transaminases returned to
      normal levels. We also provide a review of other cases to date documenting
      possible cases of daptomycin-induced liver injury.

PMID- 30202730
TI  - Pyeloduodenal fistula as a result of pyonephrosis.

PMID- 30202731
TI  - Ureteral metastasis in carcinoma of the breast.

PMID- 30202732
TI  - Late-onset rectal bleeding with hemorrhagic shock after transrectal prostate
      needle biopsy.
AB  - Late-onset rectal bleeding after transrectal prostate needle biopsy is
      potentially life-threatening. We report the case of a 75-year-old male who
      presented with severe rectal bleeding 3 days after transrectal prostate needle
      biopsy. Because the bleeding could not be arrested by conservative treatment,
      emergent colorectal endoscopic clipping (twice) and elective angiography were
      performed. Packed red blood cell transfusion (14 units in total) was required to
      treat the developed hemorrhagic shock. Colorectal endoscopy and arterial
      embolization are effective treatments for severe rectal bleeding after
      transrectal prostate needle biopsy and should be performed without hesitation.

PMID- 30202733
TI  - An unusual case of a huge hydatid cyst of ectopic pelvic kidney.

PMID- 30202734
TI  - Internal hernia secondary to robotic assisted laparoscopic prostatectomy and
      extended pelvic lymphadenectomy with skeletonization of the external iliac
      artery.

PMID- 30202735
TI  - Ureteral stent causing urinary incontinence: An unusual suspect.

PMID- 30202736
TI  - Long-term survival of a patient with pulmonary metastatic urothelial carcinoma
      following metastasectomy.
AB  - Cisplatin-based systemic chemotherapy is the gold standard for the treatment of
      patients with metastatic urothelial carcinoma (UC), which is a chemosensitive
      cancer. However, long-term survival has been deemed disappointing. We describe
      here a case of UC with solitary pulmonary metastasis who had successfully
      achieved long-term disease-free survival by combination of cisplatin-based
      chemotherapy and pulmonary metastasectomy. From the finding of this article, we
      propose that adjuvant chemotherapy may be considered as a viable option after
      metastasectomy in low volume pulmonary metastatic UC patients.

PMID- 30202737
TI  - Smoothness of the knee joint movement during the stance phase in patients with
      severe knee osteoarthritis.
AB  - Background: Patients with knee osteoarthritis can significantly affect the
      function of the knee joint in terms of joint range and mobility and have a
      stereotypical pattern of knee stiffness during gait, caused by an increased
      resistance in the muscles and soft tissues during the stance phase of knee joint
      movement. Smoothness in movement, such as during walking and running, is assumed
      to be attained by adulthood; however, disruptions in gait pattern due to injury
      or performance enhancement can alter the smoothness of the movement, and this is
      often quantified in terms of "jerk". A higher jerk value is linked with a
      decrease in smoothness. However few have reported to evaluate the smoothness of
      the knee joint movement during walking in patients with knee osteoarthritis. The
      purpose of the present study was to quantify the smoothness of the knee joint
      movement during walking in people with knee osteoarthritis. Methods: Patients
      were classified as having early or severe knee osteoarthritis. There were eight
      patients in each group (16 knees; three males, five females). The normalized
      angular jerk was calculated as an indicator of the walking knee joint smoothness
      in each of the four periods of the stance phase. Two-way ANOVA was performed to
      compare the smoothness of knee joint movement between groups and between each
      period of the stance phase. Results: The angular change in the sagittal plane of
      those with severe knee osteoarthritis was smaller than that of those with early
      knee osteoarthritis in all periods of the stance phase. Normalized angular jerk
      did not significantly differ between groups in all periods. In both groups, the
      normalized angular jerk in the sagittal plane was significantly larger in the mid
      stance and terminal stance periods than in the early stance and pre-swing
      periods. Only in patients with severe knee osteoarthritis, there was a
      significantly larger jerk in the frontal plane in the mid-stance period.
      Conclusion: The present results revealed that the smoothness of joint movement
      decreases during the single leg supporting phase of the stance phase in the
      frontal plane with severe knee osteoarthritis, although there is no difference in
      smoothness of joint movement according to the severity of knee osteoarthritis The
      instability during single leg support due to increase of the knee joint load and
      destruction cause the impaired smoothness of the knee joint movement.

PMID- 30202738
TI  - Factors influencing outcomes of nonsurgical treatment for baseball players with
      SLAP lesion.
AB  - Background/objective: Superior labrum anterior posterior (SLAP) lesion of the
      shoulder joint occurs in throwing athletes as a results of overuse, such as from
      repetitive baseball pitching. Nonsurgical treatments are usually the first-line
      therapy for symptomatic SLAP lesion. However, some patients cannot obtain
      satisfactory improvement of their symptoms, leading to dysfunction of the
      shoulder and diminished pitching performance. The purpose of this study was to
      analyze factors that influence outcomes of nonsurgical treatments for SLAP
      lesion. Methods: Forty-five baseball players with SLAP lesion, whose mean age was
      21.6 (range, 16-36) years and who underwent nonsurgical treatments, were the
      subjects of this study. SLAP lesion was diagnosed by shoulder arthrography and
      magnetic resonance imaging (MRI). Exclusion criteria included definite associated
      trauma such as dislocation, fracture or injuries related to sports activities.
      Playing positions included pitcher (21 patients), catcher (3 patients), infielder
      (13 patients) and outfielder (8 patients). Mean symptomatic duration from the
      onset of shoulder pain to the beginning of nonsurgical treatments was 8.5 (range,
      1-72) months. Nonsurgical treatments included physical therapy, such as range of
      motion, stretching, and rotator cuff exercises, as well as prescription of
      nonsteroidal anti-inflammatory drugs if necessary. To identify factors that
      influenced outcomes of nonsurgical treatments for SLAP lesion, various factors of
      13 nonresponsive patients were compared with those of 32 patients who responded
      to nonsurgical treatment. The factors were as follows: patient background, such
      as age or playing position; range of shoulder motion; shoulder joint laxity; and
      findings of radiographs and MRI. All data were statistically assessed using
      logistic analysis and Spearman's correlation coefficient. The significance level
      was set at P < 0.05, and odds ratios were determined. Results: Factors identified
      as having significant difference between the 2 groups were age, duration of
      baseball experience, symptomatic period, playing position, range of internal and
      external rotation in the first medical examination, range of total rotation of 90
      degrees  abduction 2 months after nonsurgical treatments, and presence of Bennett
      spur and partial-thickness tears of the articular-side rotator cuff. Factors with
      high odds ratios were symptomatic period, range of total rotation of 90 degrees 
      abduction 2 months after the treatment, age, and duration of baseball experience.
      Conclusion: Symptomatic period, duration of baseball experience, age, and
      findings of radiographs and MRI are inevitable factors that cannot be improved by
      nonsurgical treatment. On the other hand, restriction of shoulder motion due to
      posterior muscular tightness is a factor that can be improved by nonsurgical
      treatment. Early improvement of shoulder motion is important to obtain
      satisfactory outcomes of nonsurgical treatments for SLAP lesion.

PMID- 30202739
TI  - What should be done for men with sperm DNA fragmentation?
AB  - In an age when a small quantity of sperm can lead to pregnancy through in vitro
      fertilization or intracytoplasmic sperm injection, selecting healthy sperm is
      important. Sperm DNA fragmentation (SDF) is known to be higher in infertile men.
      Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end
      labeling (TUNEL) and the alkaline comet test are SDF tests that directly measure
      DNA damage and have shown closer correlations with assisted reproduction results
      than indirect tools such as the sperm chromatin structure assay or the sperm
      chromatic dispersion test. It is difficult; however, to endorse a single test as
      the best test overall; instead, it is best to select a testing method based on
      each patient's clinical condition and goals. In a couple struggling with
      infertility, if the male partner has a high level of SDF, he should aim to
      decrease SDF through lifestyle modifications, antioxidant treatment, and ensuring
      an appropriate duration of abstinence, and physicians need to treat the
      underlying diseases of such patients. If sperm DNA damage continues despite the
      patient's and physician's efforts, other methods, such as micromanipulation-based
      sperm selection or testicular sperm extraction, should be used to select healthy
      sperm with nuclear DNA integrity.

PMID- 30202740
TI  - Rapid freezing versus Cryotop vitrification of mouse two-cell embryos.
AB  - Objective: To compare our in-house method of embryo freezing with Cryotop
      vitrification in terms of immediate survival, subsequent cleavage and blastocyst
      formation, and cell numbers in blastocysts. Methods: Two-cell mouse embryos were
      randomly allocated into three groups: a non-frozen control group (group 1,
      n=300), a group that underwent Cryotop vitrification (group 2, n=300), and a
      group that underwent our in-house freezing method (group 3, n=300). Results:
      There were no significant differences between groups 2 and 3 in the immediate
      survival rate (96.3% vs. 98.6%, respectively; p=0.085), the further cleavage rate
      (91.7% vs. 95.0%, respectively; p=0.099), or the blastocyst formation rate (80.7%
      vs. 78.6%, respectively; p=0.437). The cell numbers in the blastocysts from
      groups 1, 2, and 3 were comparable (88.99+/-10.44, 88.29+/-14.79, and 86.42+/
      15.23, respectively; p=0.228). However, the percentage of good-quality
      blastocysts in the Cryotop vitrification group was significantly higher than in
      the group in which our in-house method was performed, but was lower than in the
      control group (58.0%, 37.0%, and 82.7%, respectively; p<0.001). Conclusion: At
      present, our method is inferior to the commercial Cryotop vitrification system.
      However, with further improvements, it has the potential to be useful in routine
      practice, as it is easier to perform than the current vitrification system.

PMID- 30202741
TI  - Associations of serum fetuin-A and oxidative stress parameters with polycystic
      ovary syndrome.
AB  - Objective: The aim of this study was to compare serum fetuin-A levels and
      oxidative stress markers, as indicators of insulin resistance, in women with
      polycystic ovary syndrome (PCOS) and in healthy controls. Methods: This
      prospective case-control study included 46 patients with PCOS and 48 age- and
      body mass index-matched control women. Levels of serum hormones, fetuin-A, and
      oxidative stress markers were measured in blood samples taken during the early
      follicular period from each participant. Results: Follicle-stimulating hormone
      (FSH), luteinising hormone (LH), total testosterone levels, and the LH/FSH ratio
      were found to be significantly higher in women with PCOS than in controls. Serum
      total antioxidant status, total oxidant status, and oxidative stress index
      parameters all indicated significantly higher levels of oxidative stress in PCOS
      patients than in controls. Serum fetuin-A levels, which were analyzed as an
      indicator of insulin resistance, were higher in the PCOS group than in the
      control group (210.26+/-65.06 ug/mL and 182.68+/-51.20 ug/mL, respectively;
      p=0.024). Conclusion: The data obtained from the present study suggest that
      higher levels of both serum fetuin-A and oxidative stress markers might be
      related with PCOS.

PMID- 30202742
TI  - Early fragment removal on in vitro fertilization day 2 significantly improves the
      subsequent development and clinical outcomes of fragmented human embryos.
AB  - Objective: To determine whether fragment removal on in vitro fertilization (IVF)
      day 2 improved the subsequent development and pregnancy outcomes of fragmented
      embryos compared to similar-grade embryos without fragment removal. Methods: This
      study was a retrospective analysis involving 191 IVF cycles in which all embryos
      had over 10% fragmentation (grade 3 or 4) on day 2 of the IVF-embryo transfer
      cycle from March 2015 to December 2017. IVF cycles were divided into the fragment
      removal group (n=87) and the no fragment removal group (n=104) as a control
      cohort. Before fragment removal, embryos with fragmentation on day 2 were
      incubated in Ca2+- and Mg2+-free biopsy medium under paraffin oil for 30 minutes.
      Microsurgical fragment removal was performed with later-assisted hatching and a
      handmade suction micropipette that had an outer diameter of 30 um. Results: There
      were no significant differences in the characteristics of the patients between
      the control and the fragment removal groups. After fragment removal and
      subsequent in vitro culture for 24 hours, the number of blastomeres (7.1+/-1.7
      vs. 6.9+/-1.6) was comparable between the transferred embryos in the two groups,
      but the morphological grade of the embryos in the fragment removal group (1.9+/
      0.7) was significantly higher than that of the control group (3.1+/-0.5, p<0.01).
      The clinical pregnancy (43.7%) and implantation rates (25.8%) in the fragment
      removal group were significantly higher than those in the control group (28.8%
      and 14.0%, respectively; p<0.05). Conclusion: Early fragment removal on day 2
      significantly improved the subsequent development and pregnancy outcomes of
      fragmented embryos.

PMID- 30202743
TI  - Thinning and drilling laser-assisted hatching in thawed embryo transfer: A
      randomized controlled trial.
AB  - Objective: In frozen and thawed embryos, the zona pellucida (ZP) can be damaged
      due to hardening. Laser-assisted hatching (LAH) of embryos can increase the
      pregnancy rate. This study compared thinning and drilling of the ZP before frozen
      embryo transfer (FET). Methods: Patients were randomly allocated into two groups
      for LAH using thinning or drilling on day 2 after thawing. Twenty-five percent of
      the ZP circumference and 50% of the ZP thickness was removed in the thinning
      group, and a hole 40 um in diameter was made in the drilling group. Results: A
      total of 171 in vitro fertilization/intracytoplasmic sperm injection FET cycles,
      including 85 cycles with drilling LAH and 86 cycles with thinning LAH, were
      carried out. The thinning group had a similar beta-human chorionic gonadotropin
      positive rate (38.4% vs. 29.4%), implantation rate (16.5% vs. 14.4%), clinical
      pregnancy rate (36.0% vs. 25.9%), miscarriage rate (5.8% vs. 2.4%), ongoing
      pregnancy rate (30.2% vs. 23.5%), and multiple pregnancy rate (7.0% vs. 10.6%) to
      the drilling LAH group. There were no significant differences in pregnancy
      outcomes between subgroups defined based on age (older or younger than 35 years)
      or ZP thickness (greater or less than 17 um) according to the LAH method.
      Conclusion: The present study demonstrated that partial ZP thinning or drilling
      resulted in similar outcomes in implantation and pregnancy rates using thawed
      embryos, irrespective of women's age or ZP thickness.

PMID- 30202744
TI  - Early gonadotropin-releasing hormone antagonist protocol in women with polycystic
      ovary syndrome: A preliminary randomized trial.
AB  - Objective: To prospectively evaluate the efficacy and safety of a fixed early
      gonadotropin-releasing hormone (GnRH) antagonist protocol compared to a
      conventional midfollicular GnRH antagonist protocol and a long GnRH agonist
      protocol for in vitro fertilization (IVF) in patients with polycystic ovary
      syndrome (PCOS). Methods: Randomized patients in all three groups (early
      antagonist, n=14; conventional antagonist, n=11; long agonist, n=11) received 21
      days of oral contraceptive pill treatment prior to stimulation. The GnRH
      antagonist was initiated on the 1st day of stimulation in the early antagonist
      group and on the 6th day in the conventional antagonist group. The GnRH agonist
      was initiated on the 18th day of the preceding cycle. The primary endpoint was
      the number of oocytes retrieved, and the secondary endpoints included the rate of
      moderate-to-severe ovarian hyperstimulation syndrome (OHSS) and the clinical
      pregnancy rate. Results: The median total number of oocytes was similar among the
      three groups (early, 16; conventional, 12; agonist, 19; p=0.111). The early GnRH
      antagonist protocol showed statistically non-significant associations with a
      higher clinical pregnancy rate (early, 50.0%; conventional, 11.1%; agonist,
      22.2%; p=0.180) and lower incidence of moderate-to-severe OHSS (early, 7.7%;
      conventional, 18.2%; agonist, 27.3%; p=0.463), especially among subjects at high
      risk for OHSS (early, 12.5%; conventional, 40.0%; agonist, 50.0%; p=0.324).
      Conclusion: In PCOS patients undergoing IVF, early administration of a GnRH
      antagonist may possibly lead to benefits due to a reduced incidence of moderate
      to-severe OHSS in high-risk subjects with a better clinical pregnancy rate per
      embryo transfer. Further studies with more subjects are required.

PMID- 30202745
TI  - Angiopoietin-1 and -2 and vascular endothelial growth factor expression in
      ovarian grafts after cryopreservation using two methods.
AB  - Objective: The favored method of preserving fertility in young female cancer
      survivors is cryopreservation and autotransplantation of ovarian tissue. Reducing
      hypoxia until angiogenesis takes place is essential for the survival of
      transplanted ovarian tissue. The aim of this study was to investigate the role of
      angiopoietin-1 (Angpt-1), angiopoietin-2 (Angpt-2), and vascular endothelial
      growth factor (VEGF) in ovarian tissue grafts that were cryopreserved using two
      methods. Methods: Ovarian tissues harvested from ICR mice were divided into three
      groups: group I (control), no cryopreservation; group II, vitrification in EFS
      (ethylene-glycol, ficoll, and sucrose solution)-40; and group III, slow freezing
      in dimethyl sulfoxide. We extracted mRNA for VEGF, Angpt-1, and Angpt-2 from
      ovarian tissue 1 week following cryopreservation and again 2 weeks after
      autotransplantation. We used reverse transcriptase-polymerase chain reaction to
      quantify the levels of VEGF, Angpt-1, and Angpt-2 in the tissue. Results: Angpt-1
      and Angpt-2 expression decreased after cryopreservation in groups II and III.
      After autotransplantation, Angpt-1 and Angpt-2 expression in ovarian tissue
      showed different trends. Angpt-1 expression in groups II and III was lower than
      in group I, but Angpt-2 in groups II and III showed no significant difference
      from group I. The vitrified ovarian tissues had higher expression of VEGF and
      Angpt-2 than the slowfrozen ovarian tissues, but the difference was not
      statistically significant. Conclusion: Our results indicate that Angpt-2 may play
      an important role in ovarian tissue transplantation after cryopreservation
      although further studies are needed to understand its exact function.

PMID- 30202746
TI  - Stem Cell Therapy in Osteonecrosis of the Femoral Head.

PMID- 30202747
TI  - Management of Periprosthetic Joint Infection.
AB  - Periprosthetic joint infection (PJI) is a serious complication after
      arthroplasty, which is associated with pain, prolonged hospital stay, multiple
      surgeries, functional incapacitation, and even mortality. Using scientific and
      efficient management protocol including modern diagnosis and treatment of PJI and
      eradication of infection is possible in a high percentage of affected patients.
      In this article, we review the current knowledge in epidemiology, classification,
      pathogenesis, diagnosis and treatment of PJI.

PMID- 30202748
TI  - Modular Stems: Advantages and Current Role in Primary Total Hip Arthroplasty.
AB  - Using modular femoral stems in total hip arthroplasty enables surgeons to make
      fine adjustments to individual joints and offers intraoperative flexibility. The
      concept of modularity has been developed in numerous shapes, resulting in a vast
      range of options. Among them, the greatest achievement has been made for
      prostheses with modular proximal sleeves. The use of these implants has resulted
      in excellent mid- to long-term results in a number of cases. Although the use of
      tapered stems with a broaching technique is gaining popularity in straightforward
      primary surgeries, modular femoral implants are still associated with a number of
      potential challenges (e.g., developmental dysplasia of the hip, infection
      sequelae, and skeletal dysplasia). Based on published results, it is advisable to
      consider it as an option for complicated cases where the proximal femur is
      severely deformed.

PMID- 30202750
TI  - Cementless Total Hip Arthroplasty Using the COREN Hip System: A Minimum Five-Year
      Follow-up Study.
AB  - Purpose: This study presents the clinical and radiological outcomes of cementless
      total hip arthroplasty using the COREN hip system after a minimum duration of
      follow-up of 5 years. Materials and Methods: We evaluated the results of a
      consecutive series of the first 200 primary total hip arthroplasties that had
      been performed in our hospital in 169 patients between February 2007 and April
      2011. Six patients (6 hips) had died within 5 years, and 12 patients (13 hips)
      had been lost to follow-up, leaving a total of 151 patients (181 hips) available
      for the study. All patients were evaluated clinically and radiologically with
      special attention to thigh pain, implant fixation, radiolucent line and
      osteolysis around implants. Results: The mean Harris hip score improved from 59.4
      preoperatively to 97.2 postoperatively. No patient complained of thigh pain. All
      implants demonstrated radiographic evidence of stable fixation by bone ingrowth
      without any change in position. No implant was loose radiographically or was
      revised. Eleven hips (7.7%) had a radiolucent line around the femoral stem. Focal
      osteolytic area was detected in 3 cases (2.1%). An osteolytic lesion was
      stabilized in 1 case and further observation was needed in 2 cases in which the
      lesions were detected several years after surgery. Stress shielding was observed
      in 80.3% of cases (first degree, 35.9%; second degree, 44.4%); there were no
      cases of third or fourth degree stress shielding. One case was complicated by
      bacterial infection and repeated dislocation. Conclusion: Mid-term results of
      total hip arthroplasty using the COREN hip system are very encouraging clinically
      and radiologically.

PMID- 30202749
TI  - Revision Total Hip Arthroplasty after Ceramic Bearing Fractures in Patients Under
      60-years Old; Mid-term Results.
AB  - Purpose: Although advances in technology have reduced the risk of ceramic implant
      fractures in total hip arthroplasty, these injuries do occur and their treatment
      remains challenging. There is a lack of studies reporting on the effectiveness of
      ceramic components in revision hip arthroplasty after ceramic bearing fracture.
      The aim of this study is to evaluate clinical and radiologic outcomes of revision
      surgery with ceramic-on-ceramic components after ceramic bearing fractures in
      young (i.e., under 60 years old) and active patients. Materials and Methods:
      Eight patients who, from May 2004 to November 2011, underwent ceramic-on-ceramic
      revision surgery following a ceramic component fracture and had more than 6 years
      follow up were enrolled in this study. All eight patients were male with mean
      ages at first and revision surgeries of 39 years (range, 31-50 years) and 43.8
      years (range, 33-60 years), respectively. There were 6 and 2 cases of ceramic
      liner and ceramic head fractures, respectively. The average time from the first
      operation to revision surgery was 54.3 months (range, 9-120 months), and the
      average follow up period was 9.7 years (range, 6-13.3 years). Results: At the
      last follow up, all patients showed improvement in Harris hip score and pain
      relief and there were no cases of loosening or osteolysis. Conclusion: Revision
      total hip arthroplasty using ceramic-on-ceramic components after ceramic
      component fracture is a feasible and appropriate surgical option in young and
      active patients.

PMID- 30202751
TI  - Local Postoperative Complications after Surgery for Intertrochanteric Fractures
      Using Cephalomedullary Nails.
AB  - Purpose: Cephalomedullary nails (CMN) are commonly used for the surgical
      treatment of intertrochanteric fractures. This study aimed to evaluate overall
      postoperative local complications by reviewing patients who received surgical
      treatment using three different types of implants. Materials and Methods: The
      study sample included 353 patients (107 males, 246 females) who underwent surgery
      using CMN for intertrochanteric fractures. Three different types of implants were
      used: i) the Gamma3(r) (Stryker) in 80 cases, ii) the Targon(r) PF (Aesculap) in
      225 cases, and iii) the Compression Hip Nail(r) (Trademedics) in 48 cases. The
      mean age was 82.6 (range, 60-109) years and the average follow-up period was 15
      (range, 6-80) months. Postoperative local complications and risk factors of cut
      out were assessed. Results: The most common complication was cut-out (n=26).
      Other complications included non-union (n=3), periprosthetic fracture (n=2),
      avascular necrosis (n=1), heterotopic ossification (n=1), and sleeve pull out
      (n=1). Multivariate analysis revealed that the cut-out group had a higher rate of
      poor reduction compared to the non-complicated group (P<0.001). Although the mean
      tip-apex distance (TAD) was 18.4 mm in the non-complicated group, lower than that
      of the cut-out group (P=0.001), multivariate analysis revealed that TAD was not a
      significant risk factor for cut-out (P=0.065). Conclusion: Cut-out is the most
      common local complication associated with surgical treatment of intertrochanteric
      fractures using CMN. Proper reduction appears to be important in lowering the
      risk of cut-out. Maintaining low TAD is another critical factor in achieving
      sufficient fixation of lag screw to the subchondral bone of the femoral head.

PMID- 30202752
TI  - Long-term Outcomes of Cemented Total Hip Arthroplasty in Patients with Ankylosing
      Spondylitis at a Minimum Follow-up of 10 Years.
AB  - Purpose: This study was performed to evaluate long-term clinical and radiologic
      outcomes of cemented total hip arthroplasty in patients with ankylosing
      spondylitis. Materials and Methods: A retrospective study of 12 patients (16
      cases) diagnosed with ankylosing spondylitis undergoing total hip arthroplasty
      with cemented femoral stem from November 2002 to January 2006 with a minimum
      follow up of 10 years. Clinical outcomes were assessed using Harris Hip Scores
      and measures of pain and range of motion. Radiologic outcomes were assessed with
      serial plain X-ray. Fixation and stability of implant, enthesopathy of ischium
      and development of heterotopic ossification were also evaluated. Results: Mean
      Harris Hip Scores significantly improved from pre-operative levels (58 points;
      range, 39-81 points) to post-operative (92 points; range, 68-100 points). Mean
      flexion contracture levels decreased from preoperative (13 degrees ) to post
      operative (5 degrees ), and mean post-operative range of motion improved 106
      degrees  compared to preoperative levels. No newly developed osteolysis lesions
      or implant loosening were observed in last follow up X-rays. One heterotopic
      ossification and one greater trochanter fracture were observed. Greater
      trochanter fracture was treated conservatively, and was resulted in bony union.
      No patients underwent revisions. Conclusion: This study revealed positive long
      term clinical and radiologic outcomes following total hip arthroplasty with
      cemented femoral stems in patients with ankylosing spondylitis patients.

PMID- 30202753
TI  - Acetabular Subchondral Bone Decortication and Its Role in the Outcome of Cemented
      Total Hip Replacement in Young Patients.
AB  - Purpose: Long-term fixation of cemented acetabular components can be problematic
      in younger active patients. Our technique is put forward to improve outcomes and
      maximize implant survivorship in this particular patient population. Materials
      and Methods: We report on a cohort of young adult patients (less than 55 years
      old) with cemented total hip replacement (THR) using a novel technique in
      preparing and cementing the acetabulum with a minimum follow-up of 10 years (mean
      follow-up, 14 years). Retrospectively collected data on clinical and radiological
      outcomes were reviewed. Results: Sixty-five THRs were performed with the minimum
      study follow-up period. Average age for patients was 44 years old (range, 19-55
      years). The mean Hip Disability and Osteoarthritis Outcome Score for patients at
      final appointment was 92.7. Radiographs taken at an average of 14 years after
      operation showed 63 of 65 hips showed no evidence of any radiological loosening.
      Cup survivorship was 100% at the end of the study period. Conclusion: Our
      technique of preparing the acetabulum in combination with cement fixation is
      reproducible with excellent results in a cohort of patients prone to early
      aseptic loosening of the acetabular component.

PMID- 30202754
TI  - Late Onset Disassembly of a Modular Neck-stem Component after Cementless Hip
      Replacement without Dislocation: A Case Report and Review of Literatures.
AB  - Modular femoral prostheses are characterized by a second neck-stem junction. This
      modularity provides many clinical benefits including hip offset restoration,
      intraoperative leg length and anteversion adjustment. Although, this extra
      junction in modular femoral prostheses can contribute to catastrophic
      consequences like fracture, cold welding, corrosion and fretting of the
      modularity. However, only few complications related to the modularity itself have
      been reported in the literature. We report a unique case of neck-stem component
      dissociation without dislocation of the R-120PCTM Modular Stem (DJO Surgical).
      Our 71-year-old obese female patient underwent cementless hip replacement 5 years
      ago. Following radiographic confirmation of neck-stem dissociation open reduction
      was performed and wiring fixation was applied to secure the neck to the stem.
      After reduction and fixation, hip joint was stable, and our patient returned to
      her daily routine 2.5 months postoperatively. The last follow up was at 12 months
      after surgery with excellent radiographic and clinical evaluation.

PMID- 30202755
TI  - Klotho and Postmenopausal Hormone Replacement Therapy in Women with Chronic
      Kidney Disease.
AB  - Kidney function is highly susceptible to age-related changes, with chronic kidney
      disease (CKD) serving as an important cause of morbidity and mortality in older
      patients. The prevalence of CKD in Korea is higher among the elderly, relative to
      the general population, with the most significant increases seen following the
      onset of menopause. Under normal conditions, estrogen attenuates renal superoxide
      production and protects the kidney from oxidative damage. As estrogen levels are
      known to decrease by as much as 80% during menopause, this represents a
      significant risk for older women. Postmenopausal hormone replacement therapy
      (HRT) modulates the renin-angiotensin system, thereby reducing the progressive
      deterioration of renal function. Use of estrogen-based HRT has been shown to
      ameliorate renal function in postmenopausal women, and delay CKD progression.
      Renal expression of klotho, an important suppressor of aging, is markedly
      decreased in CKD patients, making it a promising candidate for use as a
      prognostic biomarker in CKD. Here, we review the key links between renal
      function, sex, age, and estrogen levels during menopause, and discuss the use of
      postmenopausal HRT in CKD attenuation.

PMID- 30202756
TI  - Comparative Study on Hysteroscopic and Histologic Examinations of the Endometrium
      in Postmenopausal Women Taking Tamoxifen.
AB  - Objectives: To evaluate the histologic effects of tamoxifen on the endometrium
      using hysteroscopy in postmenopausal women with breast cancer. Methods: The study
      included 46 postmenopausal patients who were referred from another clinic due to
      thickening or bleeding of the endometrium after taking tamoxifen for breast
      cancer. All patients underwent transvaginal sonography (TVS) and hysteroscopic
      endometrial biopsy with a 5-mm, continuous-flow, operating hysteroscope. Results:
      The incidence of malignancy was high (20%) in cases of abnormal uterine bleeding
      (AUB) after taking tamoxifen. However, in the non-AUB group with thick
      endometrium after taking tamoxifen, the incidence of adenocarcinoma was 3.2%.
      Conclusions: Our findings confirm the estrogen-like effect of tamoxifen on the
      endometrium. Endometrial evaluation with TVS suggests further diagnostic
      procedures; moreover, histologic examination is necessary under hysteroscopy,
      especially in cases of endometrial bleeding after taking tamoxifen.

PMID- 30202758
TI  - A Systematic Review and Meta-analysis on the Effect of Herbal Medicine to Manage
      Sleep Dysfunction in Peri- and Postmenopause.
AB  - Objectives: Some conventional medications used to treat insomnia, such as
      benzodiazepine, non-benzodiazepine, and hormone therapy, are associated with side
      effects. Therefore, there is a growing interest in the use of herbal medicine.
      The aim of this systematic review is to assess the effects herbal medicines have
      on sleep disorders of peri- and postmenopausal women. Methods: Three databases
      were searched including MEDLINE, Scopus, and the Cochrane Library from inception
      to March 2018. Results: Six trials assessed the effect of soy on sleep disorders.
      Forrest plot for 2 studies showed that the standardized mean difference (SMD) of
      the sleep problems was lower in the soy group than the placebo group (SMD = 
      0.996; P < 0.001; 95% confidence interval, -1.42 to -0.563). Three trials showed
      soy had no significant effect on sleep disorders and one study showed a positive
      effect on sleep disorders. Accordingly, it is difficult to reach a definite
      conclusion regarding the effects of soy on sleep disorders based on these
      findings. According to a trial, significant beneficial effect associated with
      taking Schisandra chinensis. Findings suggested that some herbal medicines like
      red clover, lavender combined with bitter orange and pin bark extract had
      attenuating effects on sleep disorders. After intake of 530 mg of valerian twice
      a day for one month, statistically significant effects were observed regarding
      the quality of sleep of postmenopausal women. Conclusions: The present systematic
      review and meta-analysis found inadequate evidence to draw conclusions regarding
      the effectiveness of herbal medications, especially soy.

PMID- 30202757
TI  - Quality of Life of Postmenopausal Women in Urban and Rural Communities.
AB  - Objectives: Menopause is a transitional time in a woman's life leading to both
      physical and emotional challenges which affects the quality of life (QOL).
      Average age of menopause is around 48 years but it strikes Indian women at the
      age of 40 to 45 years. So, menopausal health demands higher priority in Indian as
      well as global scenario. The present study was conducted to compare the QOL of
      postmenopausal women residing in urban and rural communities. Methods: The study
      adopted quantitative research approach with comparative survey design. The
      samples were 100 postmenopausal women from rural urban communities selected using
      non probability purposive sampling technique. Data was collected by interview
      using demographic performa and menopause specific QOL. Results: The mean QOL
      score (X2 = 27.24) of rural women was higher than the mean QOL score (X1 = 26.34)
      of urban women. The calculated independent 't' value (t = 0.86; P < 0.05) is
      lesser than the table value (t98 = 1.980). There was association between QOL of
      urban postmenopausal women and monthly income of the family (chi2 = 4.023) was
      statistically significant at 0.05 levels. Conclusions: There was no significant
      difference in the QOL of postmenopausal women in rural and urban areas. Indian
      women are ignorant about the changes taking place in their reproductive system.
      Religion and culture of our society also inhibits to express these changes.
      Health care professionals have a great role in addressing these issues to prepare
      women to face the challenges of reproductive health.

PMID- 30202759
TI  - The Association between Oligomenorrhea, Onset of Menopause and Metabolic Syndrome
      in Thai Postmenopausal Women.
AB  - Objectives: This study explored the association between a history of
      oligomenorrhea and onset of menopause and metabolic parameters. Methods: The
      study population was 605 postmenopausal women who were patients at the Menopause
      Clinic, Maharaj Nakorn Chiang Mai Hospital, Chiang Mai, Thailand between February
      2015 and December 2015. A questionnaire was used to ask all women about their
      history of oligomenorrhea. The study also collected medical data, including
      weight, height, waist circumference, blood pressure, and blood glucose and lipid
      profile. Results: Of the 231 postmenopausal women with a complete data record, 31
      had a history of oligomenorrhea and 200 did not. The age of onset of menopause
      was around 48 years in both groups. Prevalence of metabolic syndrome was 12.1%.
      More women with a waist circumference larger than 80 cm had a history of
      oligomenorrhea at the interview than women who had not, but a history of
      oligomenorrhea did not relate to other metabolic parameters. The adjusted odds
      ratio of a history of oligomenorrhea to waist circumference was 3.69 (95%
      confidence interval, 1.17-11.64). Conclusions: A history of oligomenorrhea did
      not affect the age at menopause, but was associated with waist circumference
      during menopause.

PMID- 30202761
TI  - Overview of the Effect of Herbal Medicines and Isoflavones on the Treatment of
      Cognitive Function.
AB  - Objectives: The current overview aimed to present the effect of herbal medicines
      on cognitive function among menopausal women. Methods: Two separate authors
      performed systematic search of the 3 databases of (the MEDLINE Scopus and the
      Cochrane Central Register Trials) from inception to January 2018. Methodological
      quality of each study was assessed using the AMSTAR. Results: According to 2
      reviews, soy seems to be effective in enhancing summary cognitive function and
      visual memory. The effect of isoflavones on cognition was affected by treatment
      duration as six weeks of treatment improved some dimensions of cognitive
      parameters, including mental flexibility and planning, and longer treatment
      period (6 months) improved category digit span test, digit symbol test, and
      visual scanning test score. The effect of phytoestrogen on cognitive function of
      menopausal women might be altered age, gender, ethnicity, menopausal status,
      dosage, and length of treatment, types of cognitive test, location, types of soy,
      and types of phytoestrogen. Combination of Gingko with ginseng could not improve
      sustained attention, episode memory, category generation or frontal lobe
      function. Gingko biloba had no significant effect on planning, memory and
      sustained attention, except for its limited effect on mental flexibility in late
      menopause. In addition, other herbal medicines like black cohosh showed no
      effective beneficial. Conclusions: Phytoestrogen, soy and isoflavones might have
      a limited beneficial effect on some aspects of cognition. The phytoestrogens
      affecting cognition might be modified by age, gender, ethnicity, menopausal
      status, dosage, and length of treatment, types of cognitive test, location, types
      of soy, and types of phytoestrogen.

PMID- 30202760
TI  - Comparison of Anogenital Distance and Correlation with Vulvo-vaginal Atrophy: A
      Pilot Study on Premenopausal and Postmenopausal Women.
AB  - Objectives: Anogenital distance (AGD) represents the space between labia
      posterior commissure and anus. This was pilot study to investigate how menopause
      and so lack of oestrogens affects AGD. Methods: A total of 109 patients were
      enrolled. AGD was measured in lithotomy position using sterile paper ruler.
      Anogenital index (AGI) was used to control 2 variables of height and weight (body
      mass index, kg/m2). Vaginal health index (VHI) was used to evaluate vaginal
      wellness. Female sexual function index (FSFI) questionnaire was administered to
      all women to evaluate the impact of menopause on their sexual function. Results:
      AGD (30.87 +/- 2.98 vs. 17.57 +/- 2.18; P = 0.0001) and AGI (1.40 +/- 0.21 vs.
      0.70 +/- 0.15; P = 0.0001) were both significantly lower in the postmenopausal
      group. Postmenopausal women were affected by vulvovaginal atrophy (VVA)
      significantly. Thus, VHI scores were dramatically worse in postmenopausal group
      (23.95 +/- 1.28 vs. 10.75 +/- 3.41; P = 0.0001) as well as FSFI results (32.68 +/
      2.25 vs. 19.78 +/- 5.46; P = 0.0001). Conclusions: This study confirms that AGD
      in post-menopausal women was significantly shorter than AGD in premenopausal
      women, correlating with an increase of VVA and sexual impairment. Changes of AGD
      and AGI demonstrated to predict hormonal changes that may occur after menopause.

PMID- 30202762
TI  - Vitamin D Status and Vitamin D Receptor Gene Polymorphisms Are Associated with
      Pelvic Floor Disorders in Women.
AB  - Objectives: To investigate if vitamin D receptor (VDR) gene polymorphisms and
      circulating vitamin D levels are associated with pelvic floor disorders (PFDs).
      Methods: In this case-control study, 25-hydroxy-vitamin D (25[OH]D) serum levels
      were analyzed in 47 females with PFDs and 87 healthy females (controls),
      respectively. The VDR gene polymorphisms were determined by using polymerase
      chain reaction and performing digestions with 4 restriction enzymes i.e., ApaI,
      TaqI, FokI, and BsmI. Vitamin D levels of patients were divided into <20 ng/mL,
      20 to 30 ng/mL, and >=30 ng/mL categories. Results: Our correlative analysis of
      VDR polymorphisms as a function of the presence of PFD showed that ApaI and BsmI
      polymorphisms were significantly associated with PFD in vitamin-D-deficiency and
      insufficiency groups (P < 0.05). Mean vitamin D levels did not differ between the
      PFD case (13.01 +/- 0.84 ng/mL) and control (15.11 +/- 1.04 ng/mL) groups (P >
      0.05). However, there was a significant difference in the distribution of vitamin
      D levels between study group and controls using Pearson's chi2 test (<20 ng/mL,
      20-30 ng/mL, and >30 ng/mL: 87.2%, 12.8%, and 0% in the study group and 75.9%,
      16.1%, and 8.0% in controls, respectively, P < 0.05). Taken together, our
      observations suggest that vitamin D levels could be associated with PFDs and that
      2 polymorphisms (i.e., ApaI and BsmI) in the VDR gene may contribute to an
      increased prevalence of PFDs in women with insufficient levels of vitamin D.
      Conclusions: Examining vitamin D levels and performing a VDR genotype analysis
      may be helpful for assessing PFD risk.

PMID- 30202763
TI  - Effect of Aromatherapy on the Treatment of Psychological Symptoms in
      Postmenopausal and Elderly Women: A Systematic Review and Meta-analysis.
AB  - Objectives: To critically assess the effect of aromatherapy on the psychological
      symptoms as noted in the postmenopausal and elderly women. Methods: Three
      following databases were systematically searched: MEDLINE, Scopus and Cochrane
      Library (Cochrane Central Register of Controlled Trials) from inception to
      January 2018. The search keywords included 'menopause' AND (aromatherapy),
      without language restrictions. Results: In this study, 4 trials were included
      which fit into our systematic review. The findings demonstrated that the
      aromatherapy massage have significantly improved psychological symptoms in
      menopausal and elderly women as compared to the control group (standardized mean
      difference [SMD] = -1.24; 95% confidence interval, -0.188 to -0.606; P < 0.001
      random effect model; 3 trials, moderate to high heterogeneity, I2 = 0.76; P =
      0.028). According to 1 of the trials, the aromatherapy oil massage was no more
      effective than the untreated group regarding their experience of symptoms such as
      nervousness. Conclusions: The aromatherapy may be beneficial in attenuating the
      psychological symptoms that these women may experience, such as anxiety and
      depression, but it is not considered as an effective treatment to manage
      nervousness symptom among menopausal women. This finding should be observed in
      light of study limitations.

PMID- 30202764
TI  - Multiple Synchronous Lesions in the Genital Tract of a Female: A Rare Combination
      with Unrelated Histogenesis.
AB  - Presenting a case of endometrioid adenocarcinoma of the endometrium, benign
      cystic teratoma of one ovary, fibrothecoma in the other ovary and adenomyosis in
      the uterus. Such a combination of synchronous lesion is very rare and is not
      reported in the English medical literature.

PMID- 30202765
TI  - Erratum to: Sexual Disharmony in Menopausal Women and Their Husband: A
      Qualitative Study of Reasons, Strategies, and Ramifications.
AB  - [This corrects the article on p. 41 in vol. 24, PMID: 29765926.].

PMID- 30202766
TI  - Investigation of postoperative hypernasality after superiorly based posterior
      pharyngeal flap.
AB  - Background: Velopharyngeal insufficiency that accompanies speech resonance and
      articulation disorders can be managed through several intervention methods such
      as speech-language therapy, prosthetic aids, and surgery. However, for patients
      with severe hypernasality, surgical interventions are highly recommended. Among
      available surgical techniques, the posterior pharyngeal flap is most common. Case
      presentation: Two adult males with high nasalance scores underwent superiorly
      based posterior pharyngeal flap surgery, followed by speech testing by an expert
      speech-language therapist. Nasalance scores and articulation accuracy were
      assessed up until 1 year after the surgery. Nasalance scores were measured five
      times using a nasometer, after which the average value was calculated.
      Conclusions: Consistent declines in hypernasality over time are not easy to
      explain since the pedicled pharyngeal flap narrowed over time, secondary to
      cicatrization. However, scar tethering of the soft palate in a posterior
      direction could reduce the velopharyngeal port size over time. Therefore, long
      term follow-up with intensive speech therapy is suggested for patients with
      severe hypernasality.

PMID- 30202767
TI  - Long-Term Radiographic Adaptations to Stress of High-Level and Recreational Rock
      Climbing in Former Adolescent Athletes: An 11-Year Prospective Longitudinal
      Study.
AB  - Background: In the past few years, competition climbing has grown in popularity,
      and younger people are being drawn to the sport. Purpose: While radiographic
      changes in long-term climbers are known, there are little data available on
      adolescent climbers. The question arises as to whether climbing at high levels at
      a young age leads to radiographic changes and possibly an early onset of
      osteoarthritis of the finger joints. Study Design: Cohort study; Level of
      evidence, 2. Methods: A total of 19 members of the German Junior National Team
      (GJNT group) and 18 recreational climbers (RC group) were examined clinically and
      radiographically in 1999. In 2011, these climbers were re-examined (mean follow
      up, 11.3 +/- 1.2 years). Radiographs were evaluated using a standard protocol,
      searching for physiological adaptations such as cortical thickness of the middle
      phalanx and an increased adopted Barnett-Nordin index, as well as for early-onset
      osteoarthritic changes of the hand. In contrast to the Kellgren-Lawrence scale,
      subchondral sclerosis was added to the group of physiological, adaptive stress
      reactions and was not defined as osteoarthritis. Osteoarthritis was defined by a
      Kellgren-Lawrence grade >=2. Results: Overall, 15 of 19 (follow-up rate, 78.9%)
      climbers in the GJNT group and 13 of 18 in the RC group (follow-up rate, 72.2%),
      with a mean age of 26.8 years, were examined at the 11-year follow-up. Five
      climbers (33%) in the GJNT group presented with a decreased range of motion for
      the finger joints, in contrast to only 1 climber (8%) in the RC group.
      Radiographic stress reactions of the hand were found in 80% of the GJNT group and
      46% of the RC group, including cortical hypertrophy (GJNT: 73%; RC: 23%),
      subchondral sclerosis (GJNT: 80%; RC: 31%), a broadened proximal interphalangeal
      joint base (GJNT: 67%; RC: 38%), and a broadened distal interphalangeal joint
      base (GJNT: 53%; RC: 31%). Training intensity in 1999 and body weight in 1999
      were significant for the development of radiographic stress reactions in 2011 (P
      < .05 for both). Signs of early-stage osteoarthritis were seen in 6 climbers: 4
      (27%) in the GJNT group and 2 (15%) in the RC group. Significant statistical
      influences for the development of early-onset osteoarthritis were found for
      overall total training years (P = .024), use of campus board training in 1999 (P
      = .033), and climbing level (P = .030). Conclusion: One-quarter of climbers who
      performed at a high level in their youth showed a "mild" form of osteoarthritis
      (Kellgren-Lawrence grade 2). In analyzing the training regimens of our climbers
      for longer than 10 years, we conclude that intensive finger training (eg, campus
      board training) can lead to early-onset osteoarthritis of the hand. We also
      demonstrate that a high Union Internationale des Associations d'Alpinisme (UIAA)
      climbing level correlates with the risk for early-onset osteoarthritis of the
      hand and therefore must be seen as a risk factor for developing early-onset
      osteoarthritis of the finger joints.

PMID- 30202768
TI  - Shoulder Instability: Interobserver and Intraobserver Agreement in the Assessment
      of Labral Tears.
AB  - Background: The glenohumeral joint combines large range of motion and
      insufficient bony stabilization, making it susceptible to instability and
      dislocations. Arthroscopic surgery is routinely used as a diagnostic tool and has
      been considered the gold standard for the diagnosis of shoulder lesions. However,
      several studies have demonstrated variability in intraobserver and interobserver
      agreement. Purpose: To evaluate interobserver and intraobserver agreement in the
      assessment of intra-articular lesions associated with shoulder instability among
      fellowship-trained shoulder surgeons. Study Design: Cohort study (diagnosis);
      Level of evidence, 3. Methods: A total of 24 arthroscopic videos from patients
      treated for recurrent shoulder instability were shown to a group of 10 fellowship
      trained shoulder surgeons who are members of the Multicenter Orthopaedic Outcomes
      Network (MOON) Shoulder Group. They were presented to the surgeons on 2 different
      occasions at least 2 months apart. They were asked to classify labral tears by
      their position, type, extension, other intra-articular abnormality, and preferred
      treatment. No patient history or physical examination data were provided. The
      primary outcome was the median overall percentage of agreement for the surgeons
      performing a video review, measured for each variable evaluated. Intraclass
      correlation coefficients were used to evaluate continuous variables, and kappa
      values were used for categorical items. Results: Interobserver agreement was good
      for anterior labral lesions; good for Hill-Sachs lesions; and moderate for
      lesions of the superior labrum, posterior labrum, anterior sublabral foramen, and
      position and extension of the tear. Intraobserver agreement was either good or
      very good for all variables evaluated, except for being poor for inferior labral
      lesions and moderate for lesions of the meniscoid superior labrum. Conclusion:
      Interobserver and intraobserver reliability for the arthroscopic assessment of
      labral tears in patients with recurrent shoulder instability were good to
      moderate for the majority of anatomic structures assessed. There was relatively
      good agreement between shoulder instability surgeons on assessing and documenting
      shoulder instability-associated abnormalities. These findings are important when
      interpreting collaborative clinical cohort studies with numerous surgeons
      involved in the research.

PMID- 30202769
TI  - Prevalence and Epidemiology of Injuries Among Elite Cyclists in the Tour de
      France.
AB  - Background: Cycling injuries are increasing, particularly among elite athletes
      during major events such as the Tour de France. Many athletes miss considerable
      time from sport and require surgical intervention. Little is known about the
      epidemiology of injuries to guide practice participation strategies, return-to
      competition expectations, and injury prevention protocols. Purpose: To evaluate
      the injury epidemiology, operative incidence, and return-to-competition timeline
      among all elite cyclists participating in the 21-stage Tour de France race over a
      span of 8 years. Study Design: Descriptive epidemiological study. Methods: All
      injuries sustained during 1584 unique rides by cyclists participating in the Tour
      de France from 2010 to 2017 were evaluated. In the absence of an established Tour
      de France injury database, demographic, injury, surgical, and return-to
      competition details from all athletes who withdrew because of a traumatic injury
      were retrospectively compiled using publicly available data, which were cross
      referenced for validity. The inclusion criterion consisted of any cyclist who
      withdrew from the Tour de France because of an injury; cyclists who withdrew for
      noninjury reasons were excluded. Independent variables included injury
      demographics, missed days, and whether the injury required surgery. Injury
      prevalence, relative frequency distributions, and sample proportions were
      dependent metrics for this investigation. Results: Among the 1584 cycling entries
      evaluated over the 8-year study period, there were 259 cyclists (16%) who
      withdrew (17 cyclists/year). A total of 138 withdrawals were caused by acute
      trauma, 49% of which were fractures (n = 67), which represented the most common
      reason for withdrawal. A total of 29 (43%) cyclists with fractures underwent
      surgery. The most commonly fractured bones were the clavicle (n = 21), followed
      by the wrist (n = 6), hand (n = 5), femur (n = 5), humerus (n = 5), and ribs (n =
      5). Cyclists who underwent operative fracture fixation had a longer time between
      the injury and their next race compared with those who did not undergo surgery
      (77 vs 44 days, respectively; P = .065). Conclusion: The most common injury
      leading to withdrawal from the Tour de France over the study period was acute
      fracture, comprising 49% of all injuries. Almost half of the cyclists with
      fractures underwent surgery. The clavicle was the most commonly fractured bone.
      For cyclists who underwent operative treatment of their fractures, return to
      competition was more than 1 month longer than for those who did not. A
      prospective database is warranted to catalog injuries among these elite cyclists.

PMID- 30202770
TI  - Clofazimine in Nontuberculous Mycobacterial Infections: A Growing Niche.
AB  - Infection secondary to rapidly growing mycobacteria (RGM) is associated with
      significant morbidity and mortality, especially in individuals with underlying
      structural lung disease or immune compromise. Such infections, particularly those
      caused by the Mycobacterium abscessus group, are challenging to treat due to high
      virulence, antibiotic resistance, and the lack of effective and tolerable
      therapies. Although novel antimycobacterials are under development, clofazimine-a
      drug historically administered as part of multidrug therapy regimens for
      Mycobacterium leprae-holds promise as a chemotherapeutic for the treatment of
      RGM. The history, pharmacologic properties of clofazimine, as well as in vitro
      and in vivo studies against RGM are described here and highlight a potential new
      niche for an old drug.

PMID- 30202771
TI  - A Retrospective Analysis of the Long-Term Outcome of Drug-Resistant Epilepsy in
      Children Treated in Urban India.
AB  - Objective: To study the outcome of childhood-onset drug-resistant epilepsy.
      Methods: Fifty-five patients with drug-resistant epilepsy, meeting inclusion
      criteria, were identified from the Pediatric Neurology Clinic database with
      seizure onset less than age 13 years and a minimum follow-up of 5 years. Seizure
      remission was defined as no more than 1 seizure/year. Kaplan-Meier analysis was
      used to calculate the annual probability of seizure remission. Chi-square/Kruskal
      Wallis tests were used to detect differences in predictors between those with
      seizure remission, >=75% improvement and <75% improvement based on caregiver
      reports. Results: Median follow-up was 11 years. Of 55, 22 (40%) were in seizure
      remission at last contact; 14 (25.4%) improved by >=75%; 19 (34.5%) experienced
      <75% improvement. Annual remission probability was 3% in IQ >=70 group and 2.48%
      in IQ <70 group (P = .126). Conclusion: This study shows patients with drug
      resistant epilepsy treated in urban India can expect an overall remission rate of
      2% per year starting from the third year of follow-up.

PMID- 30202772
TI  - A Direct Comparison of IV and ICV Delivery Methods for Gene Replacement Therapy
      in a Mouse Model of SMARD1.
AB  - Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is an infantile
      autosomal recessive disease caused by the loss of the ubiquitously expressed
      IGHMBP2 gene. SMARD1 causes degeneration of alpha-motor neurons, resulting in
      distal muscle weakness, diaphragm paralysis, and respiratory malfunction. We have
      reported that delivery of a low dose of AAV9-IGHMBP2 to the CNS results in a
      significant rescue of the SMARD1 mouse model (nmd). To examine how a delivery
      route can impact efficacy, a direct comparison of intravenous (IV) and
      intracerebroventricular (ICV) delivery of AAV9-IGHMBP2 was performed. Using a low
      dose, both IV and ICV delivery routes led to a significant extension in survival
      and increased body weight. Conversely, only ICV-treated animals demonstrated
      improvements in the hindlimb muscle, neuromuscular junction, and motor function.
      The hindlimb phenotype of IV-treated mice resembled the untreated nmd mice. We
      investigated whether the increased survival of IV-treated nmd mice was the result
      of a positive impact on the cardiac function. Our results revealed that cardiac
      function and pathology were similarly improved in IV- and ICV-treated mice. We
      concluded that while IV delivery of a low dose does not improve the hindlimb
      phenotype and motor function, partial restoration of cardiac performance is
      sufficient to significantly extend survival.

PMID- 30202773
TI  - Bone-Targeted Alkaline Phosphatase Treatment of Mandibular Bone and Teeth in
      Lethal Hypophosphatasia via an scAAV8 Vector.
AB  - Hypophosphatasia is an inherited disease caused by mutations in the gene encoding
      tissue-nonspecific alkaline phosphatase (TNALP), the major symptom of which is
      hypomineralization of the bones and teeth. We had recently demonstrated that
      TNALP-deficient (Akp2-/- ) mice, which mimic the phenotype of the severe
      infantile form of hypophosphatasia, can be treated by intramuscular injection of
      a self-complementary (sc) type 8 recombinant adeno-associated virus (rAAV8)
      vector expressing bone-targeted TNALP with deca-aspartates at the C terminus
      (TNALP-D10) via the muscle creatine kinase (MCK) promoter. In this study, we
      focused on the efficacy of this scAAV8-MCK-TNALP-D10 treatment on the mandibular
      bone and teeth in neonatal Akp2-/- mice. Upon scAAV8-MCK-TNALP-D10 injection, an
      improvement of mandibular growth was observed by X-ray analysis. Micro-computed
      tomography analysis revealed progressive mineralization of the molar root in the
      treated Akp2-/- mice, and morphometric parameters of the alveolar bone were
      improved. These results suggest that the mandibular bones and teeth of
      hypophosphatasia were effectively treated by muscle directed rAAV-mediated TNALP
      D10 transduction. Our strategy would be promising for future hypophosphatasia
      gene therapy because it induces dentoalveolar mineralization and reduces the risk
      of tooth exfoliation.

PMID- 30202774
TI  - Utilization Outcomes of a Pilot Primary Care Team Redesign.
AB  - Objectives: To evaluate the effect of a team-based primary care redesign on
      primary care, emergency department (ED) and urgent care (UC) utilization, and new
      patient access to primary care. Study Design: A retrospective pre-post difference
      in-differences analysis of utilization outcomes for patients on a redesigned
      primary care team compared to a standard primary care group. Methods: Within a
      patient-centered medical home, a pilot team was developed comprising 2 colocated
      "teamlets" of 1 physician, 1 nurse practitioner (NP), 1 registered nurse (RN),
      and 2 licensed practical nurses (LPNs). The redesigned team utilized physician-NP
      comanagement, expanded roles for RNs and LPNs, and dedicated provider time for
      telephone and e-mail medicine. We compared changes in number of office, ED, and
      UC visits during the implementation year for patients on the redesigned team
      compared to patients receiving the standard of care in the same clinic.
      Proportion of new patient visits was also compared between the pilot and the
      control groups. Results: There were no differences between the redesign group and
      control group in per-patient mean change in office visits (Delta = -0.04 visits
      vs Delta = -0.07; P = .98), ED visits (Delta = 0.00 vs Delta = 0.01; P = .25), or
      UC visits (Delta = 0.00 vs Delta = 0.05; P = .08). Proportion of new patient
      visits was higher in the pilot group during the intervention year compared to the
      control group (6.6% vs 3.9%; P < .0001). Conclusions: The redesign did not
      significantly impact ED, UC, or primary care utilization within 1 year of follow
      up. It did improve access for new patients.

PMID- 30202776
TI  - Experimental datasets on properties of river sand as an aggregate in replacement
      of crushed rock for interlocking stones production.
AB  - The data explored the assessment of the quality of river sand as an aggregate in
      replacement of crushed stones which are widely used by majority of manufacturers
      in production of interlocking stones. Experimental tests carried out on river
      sand and crushed rock as aggregates include: Grain size distribution, Specific
      gravity, moisture content determination and Bulk density to determine the quality
      behavior parameters and (compressive strength) to determine the strength
      parameters. The data of the experiments are presented in Tables and Bar charts.

PMID- 30202775
TI  - Geographical Differences in Perceived Health Status Among Older Adults in Ghana:
      Do Gender and Educational Status Matter?
AB  - Studies have constantly reported mixed evidence on the associations between
      rural/urban differences and self-rated health (SRH) status among older
      populations. More importantly, the roles of other relevant sociodemographic
      characteristics such as gender and educational levels in these associations are
      mostly overlooked. The current study examines the geographical differences in SRH
      of older cohorts in Kumasi Metropolis and Bosomtwe District of Ghana. Data from a
      Spatial Health and Healthcare Study (SHHS) were analyzed using chi-square test
      and ordinal logistic regression models. Although the study discovered a
      statistically significant difference in SRH between the rural and urban samples,
      the multivariate analysis found insignificant effect in SRH between urban and
      rural samples after adjusting for theoretically relevant covariates. However, the
      interactions indicated that this association significantly strengthens for rural
      dwellers who were highly educated. Moreover, age, average monthly income,
      reporting sickness in the past 90 days, and not noticing any change in health
      status in retrospective to 12 months were independent predictors of SRH.
      Effective interventions through collaborative efforts by the Ghanaian
      sociopolitical structure and micro-level dynamics are needed to ensure holistic
      improvements in health outcomes among vulnerable older persons.

PMID- 30202777
TI  - Dataset for time-lapse ultrasonic tomography of a granite slab under uniaxial
      compression test.
AB  - This data article includes raw data for time-lapse ultrasonic tomography
      measurements during a uniaxial compression test. Two sets of experimental data
      are included: first, the ultrasonic tomography (UT) observation (i.e., waveform)
      data at each 20 MPa axial stress step during the uniaxial loading test; and
      second, the stress-strain curve of the uniaxial compression test. A numerical
      model based on the combined finite-discrete element method (FDEM) was used to
      improve the understanding of the experimental results. The model file and the
      simulated acoustic emission (AE) data extracted from the simulation results are
      also included in this article. Data sets presented in this article help to
      improve understanding of the progressive rock failure process at microscopic and
      macroscopic scales.

PMID- 30202780
TI  - Repeatedly low plasma alkaline phosphatase in a 56-year-old woman. A case of
      hypophosphatasia diagnosed in adulthood.

PMID- 30202779
TI  - Assessment of a flow cytometry technique for studying signaling pathways in
      platelets: Monitoring of VASP phosphorylation in clinical samples.
AB  - A recently released kit (PerFix EXPOSE) was reported to improve the measurement
      of the degree of phosphorylation of proteins in leukocytes by flow cytometry. We
      tested its adaptation for platelets to monitor vasodilator-stimulated
      phosphoprotein (VASP) phosphorylation, which is the basis of a currently used
      test for the assessment of the pharmacological response to P2Y12 antagonists (PLT
      VASP/P2Y12). The PerFix EXPOSE kit was compared to the PLT VASP/P2Y12 kit by
      using blood samples drawn at 24 h post clopidogrel dose from 19 patients
      hospitalized for a non-cardio-embolic ischemic stroke and treated with
      clopidogrel monotherapy for at least five days in an observational study. The
      platelet PerFix method was based on adaptation of the volume of the sample, the
      centrifugation speed and the incubation temperature. Poor agreement between
      prevention by adenosine diphosphate (ADP) of PGE1-induced cAMP-mediated VASP
      phosphorylation and ADP induced aggregation assessed by Light Transmittance
      Aggregometry was found. We found a significant correlation between the PLT
      VASP/P2Y12 kit and the PerFix EXPOSE kit. The PerFix EXPOSE kit may also be
      helpful to monitor adverse effects of second-generation tyrosine kinase
      inhibitors on platelets.

PMID- 30202778
TI  - Should sex differences be considered when applying mathematical indices and
      formulas for discriminating beta- thalassemia minor from iron deficiency?
AB  - Background: beta-thalassemia minor (BTM) and iron deficiency (ID) are common
      disorders characterized by microcytosis and/or hypochromasia, leading to a
      challenge in their discrimination during mass-screening programs especially in
      developing countries where resources are limited. It has been shown with varying
      reliability that quick exclusion of either disorder could be achieved
      mathematically using RBC-based indices and formulas. However, none of these
      proposed indices and formulas considered the sex-based hematological differences.
      This comparative retrospective study examined the efficacy of using sex-based RBC
      indices in the mathematical discrimination BTM and ID in adult males and females.
      Methods: The CBC of randomly selected eight hundred adults diagnosed with BTM or
      ID (200M & 200F BTM, and 200M & 200F ID) were used in the comparisons. The
      discrimination power, in terms of sensitivity, specificity, positive likelihood
      ratio, negative likelihood ratio, and Youden index were calculated for all
      subjects and separately for males and females for 20 mathematical indices and
      formulas. Results: Data revealed significant differences in the RBC-based indices
      between males and females for both BTM and ID groups. Significant variation in
      reliability indicators for the different indices and formulas were discovered
      between males and females samples. Conclusion: Sex-based indices and formulas are
      necessary to improve the reliability in mathematically discriminating between BTM
      and ID in mass screening programs. We also advocate for a large-scale multicenter
      study to establish the parameters of such indices and formulas with sex and age.

PMID- 30202781
TI  - Communicating the benefits of population health interventions: The health effects
      can be on par with those of medication.
AB  - How can we communicate to the public that population level health interventions
      are effective at improving health? Perhaps the most familiar "currency" of effect
      is that which can be brought about via medication. Comparisons of effect sizes
      may be effective ways of communicating the benefits of population health
      interventions if they are seen and understood in the same way that medications
      are. We developed a series of comparisons to communicate benefits of population
      health interventions in terms of similar gains to be obtained from statins,
      metformin and antihypertensive medications for prevention of cardiovascular
      events, type 2 diabetes, obesity and hypertension. A purposive search identified
      evidence of population health intervention-related benefits. This evidence ranged
      from meta-analyses of RCTs to that from observational cohort studies. Population
      health interventions included implementation of national smoke free legislation,
      enhanced neighbourhood walkability, increased opportunities for active travel and
      protection of urban green space. In some cases, the benefits of population health
      interventions were found to be equivalent to, or even outweighed those of the
      medications to which they were compared. For example, RCT-based evidence
      suggested that exercise taken with a view of a green space was associated with 12
      mmHg and 6 mmHg reductions in systolic and diastolic blood pressure,
      respectively, which was at least on par with the reductions associated with
      antihypertensive medications. Future work will test the effectiveness of these
      comparisons for increasing the familiarity, credibility and acceptability of
      population health interventions and, in particular, examine the importance of
      communicating putative mechanisms and potential co-benefits.

PMID- 30202783
TI  - Voltage-driven, local, and efficient excitation of nitrogen-vacancy centers in
      diamond.
AB  - Magnetic sensing technology has found widespread application in a diverse set of
      industries including transportation, medicine, and resource exploration. These
      uses often require highly sensitive instruments to measure the extremely small
      magnetic fields involved, relying on difficult-to-integrate superconducting
      quantum interference devices and spin-exchange relaxation-free magnetometers. A
      potential alternative, nitrogen-vacancy (NV) centers in diamond, has shown great
      potential as a high-sensitivity and high-resolution magnetic sensor capable of
      operating in an unshielded, room-temperature environment. Transitioning NV center
      based sensors into practical devices, however, is impeded by the need for high
      power radio frequency (RF) excitation to manipulate them. We report an advance
      that combines two different physical phenomena to enable a highly efficient
      excitation of the NV centers: magnetoelastic drive of ferromagnetic resonance and
      NV-magnon coupling. Our work demonstrates a new pathway that combine acoustics
      and magnonics that enables highly energy-efficient and local excitation of NV
      centers without the need for any external RF excitation and, thus, could lead to
      completely integrated, on-chip, atomic sensors.

PMID- 30202782
TI  - Is heart failure with mid range ejection fraction (HFmrEF) a distinct clinical
      entity or an overlap group?
AB  - Background: The new category of heart failure (HF), Heart Failure with mid range
      Ejection Fraction (HFmrEF) has recently been proposed with recent publications
      reporting that HFmrEF represents a transitional phase. The aim of this study was
      to determine the prevalence and clinical characteristics of patients with HFmrEF
      and to establish what proportion of patients transitioned to other types of HF,
      and how this affected clinical outcomes. Methods and results: Patients were
      diagnosed with HF according to the 2016 ESC guidelines. Clinical outcomes and
      variables were recorded for all consecutive in-patients referred to the heart
      failure service. In total, 677 patients with new HF were identified; 25.6% with
      HFpEF, 21% with HFmrEF and 53.5% with HFrEF. While clinical characteristics and
      prognostic factors of HFmrEF were intermediate between HFrEF and HFpEF, HFmrEF
      patients had the best outcome, with higher mortality in the HFrEF population (p
      0.02) and higher HF rehospitalisation rates in the HFpEF population (p <
      0.01).38.7% of the HFmrEF patients transitioned (56.4% to HFpEF and 43.6% to
      HFrEF) with fewest deaths in the patients that transitioned to HFpEF (p 0.04),
      and fewest HF readmissions in the patients that remained as HFmrEF (<0.01).
      Conclusion: HFmrEF patients had the best outcomes, compared to high rates of
      mortality seen in patients with HFrEF and high rates of HF readmissions seen in
      patients with HFpEF. Only 1/3 of HFmrEF patients transitioned during follow up,
      with the lowest mortality seen in patients transitioning to HFpEF.

PMID- 30202784
TI  - Progressive fuzzy cation-pi assembly of biological catecholamines.
AB  - Biological functions depend on biomolecular assembly processes. Assemblies of
      lipid bilayers, actins, microtubules, or chromosomes are indispensable for
      cellular functions. These hierarchical assembly processes are reasonably
      predictable by understanding chemical structures of the defined building blocks
      and their interactions. However, biopigment assembly is rather fuzzy and
      unpredictable because a series of covalently coupled intermediates from
      catecholamine oxidation pathways progressively form a higher-level hierarchy.
      This study reports a different yet unexplored type of assembly process named
      "cation-pi progressive assembly." We demonstrated for the first time that the
      cation-pi is the primary mechanism for intermolecular assembly in dopamine
      melanin biopigment. We also found that the self-assembled products physically
      grow and chemically gain new functions "progressively" over time in which cation
      pi plays important roles. The progressive assembly explains how biological
      systems produce wide spectra of pigment colors and broad wavelength absorption
      through energy-efficient processes. Furthermore, we also demonstrate surface
      independent wettability control using cation-pi progressive assembly.

PMID- 30202785
TI  - Self-folding of supramolecular polymers into bioinspired topology.
AB  - Folding one-dimensional polymer chains into well-defined topologies represents an
      important organization process for proteins, but replicating this process for
      supramolecular polymers remains a challenging task. We report supramolecular
      polymers that can fold into protein-like topologies. Our approach is based on
      curvature-forming supramolecular rosettes, which affords kinetic control over the
      extent of helical folding in the resulting supramolecular fibers by changing the
      cooling rate for polymerization. When using a slow cooling rate, we obtained
      misfolded fibers containing a minor amount of helical domains that folded on a
      time scale of days into unique topologies reminiscent of the protein tertiary
      structures. Thermodynamic analysis of fibers with varying degrees of folding
      revealed that the folding is accompanied by a large enthalpic gain. The self
      folding proceeds via ordering of misfolded domains in the main chain using
      helical domains as templates, as fully misfolded fibers prepared by a fast
      cooling rate do not self-fold.

PMID- 30202786
TI  - Pulling apart photoexcited electrons by photoinducing an in-plane surface
      electric field.
AB  - The study and control of spatiotemporal dynamics of photocarriers at the
      interfaces of materials have led to transformative modern technologies, such as
      light-harvesting devices and photodetectors. At the heart of these technologies
      is the ability to separate oppositely charged electrons and holes. Going further,
      the ability to separate like charges and manipulate their distribution could
      provide a powerful new paradigm in opto-electronic control, more so when done on
      ultrafast time scales. However, this requires one to selectively address
      subpopulations of the photoexcited electrons within the distribution-a
      challenging task, particularly on ultrafast time scales. By exploiting the
      spatial intensity variations in an ultrafast light pulse, we generate local
      surface fields within the optical spot of a doped semiconductor and thereby pull
      apart the electrons into two separate distributions. Using time-resolved
      photoemission microscopy, we directly record a movie of this redistribution
      process lasting a few hundred picoseconds, which we control via the spatial
      profile and intensity of the photoexciting pulse. Our quantitative model explains
      the underlying charge transport phenomena, thus providing a roadmap to the more
      generalized ability to manipulate photocarrier distributions with high
      spatiotemporal resolution.

PMID- 30202787
TI  - Ionic decision-maker created as novel, solid-state devices.
AB  - Decision-making is being performed frequently in areas of computation to obtain
      better performance in a wide variety of current intelligent activities. In
      practical terms, this decision-making must adapt to dynamic changes in
      environmental conditions. However, because of limited computational resources,
      adaptive decision-making is generally difficult to achieve using conventional
      computers. The ionic decision-maker reported here, which uses electrochemical
      phenomena, has excellent dynamic adaptabilities, as demonstrated by its ability
      to solve multiarmed bandit problems (MBPs) in which a gambler given a choice of
      slot machines must select the appropriate machines to play so as to maximize the
      total reward in a series of trials. Furthermore, our ionic decision-maker
      successfully solves dynamic competitive MBPs, which cause serious loss due to the
      collision of selfish users in communication networks. The technique used in our
      devices offers a shift toward decision-making using the motion of ions, an
      approach that could find myriad applications in computer science and technology,
      including artificial intelligence.

PMID- 30202788
TI  - Supplementary addendum to "Non-radiographic methods of measuring global sagittal
      balance: a systematic review"; Reliability of the Spinal Mouse in adult back pain
      sufferers.

PMID- 30202789
TI  - Recent advances in precision oncology research.

PMID- 30202790
TI  - Erratum: Author Correction: Identification and targeting of an FGFR fusion in a
      pediatric thalamic "central oligodendroglioma".
AB  - [This corrects the article DOI: 10.1038/s41698-017-0036-8.].

PMID- 30202792
TI  - Case study: patient-derived clear cell adenocarcinoma xenograft model
      longitudinally predicts treatment response.
AB  - There has been little progress in the use of patient-derived xenografts (PDX) to
      guide individual therapeutic strategies. In part, this can be attributed to the
      operational challenges of effecting successful engraftment and testing multiple
      candidate drugs in a clinically workable timeframe. It also remains unclear
      whether the ancestral tumor will evolve along similar evolutionary trajectories
      in its human and rodent hosts in response to similar selective pressures (i.e.,
      drugs). Herein, we combine a metastatic clear cell adenocarcinoma PDX with a
      timely 3 mouse x 1 drug experimental design, followed by a co-clinical trial to
      longitudinally guide a patient's care. Using this approach, we accurately predict
      response to first- and second-line therapies in so far as tumor response in mice
      correlated with the patient's clinical response to first-line therapy
      (gemcitabine/nivolumab), development of resistance and response to second-line
      therapy (paclitaxel/neratinib) before these events were observed in the patient.
      Treatment resistance to first-line therapy in the PDX is coincident with
      biologically relevant changes in gene and gene set expression, including
      upregulation of phase I/II drug metabolism (CYP2C18, UGT2A, and ATP2A1) and DNA
      interstrand cross-link repair (i.e., XPA, FANCE, FANCG, and FANCL) genes. A total
      of 5.3% of our engrafted PDX collection is established within 2 weeks of
      implantation, suggesting our experimental designs can be broadened to other
      cancers. These findings could have significant implications for PDX-based avatars
      of aggressive human cancers.

PMID- 30202793
TI  - Racial disparities in guideline-concordant cancer care and mortality in the
      United States.
AB  - Purpose: We identified the frequency of racial disparities in guideline
      concordant cancer care for select common disease sites in the United States and
      the impact of guideline concordance on mortality disparities. Methods and
      materials: Using Surveillance, Epidemiology, and End Results Medicare data, we
      evaluated patients age >65 years of black or non-Hispanic white race who were
      diagnosed with stage III breast (n = 3607), stage I (n = 14,605) or III (n =
      15,609) non-small cell lung, or stage III prostate (n = 3548) cancer between 2006
      and 2011. Chemotherapy, surgery, and radiation therapy (RT) treatments were
      identified using claims data. Pearson chi2 was used to test the associations
      between race and guideline concordance on the basis of National Comprehensive
      Cancer Network curative treatment guidelines. Mortality risks were modeled using
      Cox proportional hazards. Results: Black patients were less likely to receive
      guideline-concordant curative treatment than non-Hispanic white patients for
      stage III breast cancer postmastectomy RT (53% black, 61% white; P = .0014),
      stage I non-small cell lung cancer stereotactic radiation or surgery (61% black,
      75% white; P < .0001), stage III non-small cell lung cancer chemotherapy in
      addition to RT or surgery (36% black, 41% white; P = .0001), and stage III
      prostate cancer RT or prostatectomy (82% black, 95% white; P < .0001).
      Disparities in guideline concordance impacted racial mortality disparities.
      Specifically, hazard ratios that demonstrated elevated all-cause mortality risks
      in black patients were lowered (and more closely approached hazard ratio of 1.00)
      after adjusting for guideline concordance. A similar impact for cause-specific
      mortality was observed. Conclusions: Racial disparities in the receipt of
      curative cancer therapy impacted racial mortality disparities across multiple
      cancer sites. Benchmarking adherence to guideline-concordant care could represent
      an opportunity to stimulate improvements in disparities in cancer treatment and
      survival.

PMID- 30202791
TI  - Cardiotoxicity with vascular endothelial growth factor inhibitor therapy.
AB  - Angiogenesis inhibitors targeting the vascular endothelial growth factor (VEGF)
      signaling pathway (VSP) have been important additions in the therapy of various
      cancers, especially renal cell carcinoma and colorectal cancer. Bevazicumab, the
      first VSP to receive FDA approval in 2004 targeting all circulating isoforms of
      VEGF-A, has become one of the best-selling drugs of all times. The second wave of
      tyrosine kinase inhibitors (TKIs), which target the intracellular site of VEGF
      receptor kinases, began with the approval of sorafenib in 2005 and sunitinib in
      2006. Heart failure was subsequently noted, in 2-4% of patients on bevacizumab
      and in 3-8% of patients on VSP-TKIs. The very fact that the single-targeted
      monoclonal antibody bevacizumab can induce cardiotoxicity supports a
      pathomechanistic role for the VSP and the postulate of the "vascular" nature of
      VSP inhibitor cardiotoxicity. In this review we will outline this scenario in
      greater detail, reflecting on hypertension and coronary artery disease as risk
      factors for VSP inhibitor cardiotoxicity, but also similarities with peripartum
      and diabetic cardiomyopathy. This leads to the concept that any preexisting or
      coexisting condition that reduces the vascular reserve or utilizes the vascular
      reserve for compensatory purposes may pose a risk factor for cardiotoxicity with
      VSP inhibitors. These conditions need to be carefully considered in cancer
      patients who are to undergo VSP inhibitor therapy. Such vigilance is not to
      exclude patients from such prognostically extremely important therapy but to
      understand the continuum and to recognize and react to any cardiotoxicity
      dynamics early on for superior overall outcomes.

PMID- 30202794
TI  - Local failure and vertebral body fracture risk using multifraction stereotactic
      body radiation therapy for spine metastases.
AB  - Purpose: Single-fraction radiation surgery for spine metastases is highly
      effective. However, a high rate (20-39%) of vertebral body fracture (VBF) has
      been associated with large, single-fraction doses. We report our experience using
      multifraction stereotactic body radiation therapy (SBRT). Methods and materials:
      All patients who were treated with multifraction SBRT for spine metastases at our
      institution between 2009 and 2017 were retrospectively analyzed. SBRT was
      delivered in 2 to 5 fractions using the Cyberknife System (Accuray, Sunnyvale,
      CA). Patients were followed clinically and with magnetic resonance imaging every
      3 to 6 months. Local control, complications (including VBF), and overall survival
      were evaluated. Patient, disease, and treatment variables were analyzed for a
      statistical association with outcomes. Results: A total of 83 patients were
      treated to 98 spine lesions with a median follow-up of 7.6 months. Histologies
      included non-small cell lung cancer (NSCLC; 24%), renal cell carcinoma (RCC;
      18%), and breast cancer (12%). Surgery or vertebroplasty were performed before
      SBRT in 21% of cases. Patients received a median SBRT dose of 24 Gy in a median
      of 3 fractions. Local control was 93% at 6 months and 84% at 1 year. Higher
      prescribed dose, higher biologic effective dose, higher minimum dose to 90% of
      the planning target volume, tumor histology, and smaller tumor volume predicted
      improved local control. The cumulative dose was 23 Gy versus 26 Gy for patients
      with and without failure (P = .02), higher biologic effective dose 39 Gy versus
      46 Gy, (P = .01), and higher minimum dose to 90% of the planning target volume 23
      Gy versus 26 Gy (P = .03). VBF occurred in 4.2% of all cases and 5.3% of those
      without surgery or vertebroplasty prior to SBRT. Only preexisting VBF predicted
      risk of post-SBRT VBF (P < .01). Conclusions: Multifraction SBRT results in a
      high local control rate for metastatic spinal disease with a low VBF rate, which
      suggests a favorable therapeutic ratio compared with single-fraction SBRT.

PMID- 30202795
TI  - Implementation and utilization of hypofractionation for breast cancer.
AB  - Purpose: Hypofractionation (HF) of whole breast irradiation has become a standard
      treatment regimen because randomized trials continue to demonstrate equivalence
      in survival and local control compared with conventional fractionation. In 2011,
      the American Society for Radiation Oncology (ASTRO) adopted clinical guidelines
      on the proper selection of HF. Nevertheless, utilization remains lower than
      predicted. We evaluate the effects of clinical directives that serve as default
      treatment decisions and prospective contouring rounds on the implementation of HF
      in a large, multicenter radiation oncology department. Methods and materials: In
      2010, we implemented consensus-driven and evidence-based clinical directives to
      guide treatment decisions. Five directives were available for adjuvant breast
      cancer treatment, including conventional fractionation and HF approaches, and
      were selected on the basis of disease specifics and clinical judgment. In 2012,
      we instituted prospective contouring rounds wherein the treating physicians
      presented their directive selection and patient contours for peer-review and
      consensus opinion. For this study, charts for patients with early stage breast
      cancer were reviewed. A total of 1043 cases of breast cancer were identified.
      Patients receiving HF were analyzed on the basis of the ASTRO 2011 guidelines and
      adherence to our more inclusive clinical directives. Results: For the ASTRO
      endorsed group (n = 685), 49% of patients received HF in 2011, and 80% received
      HF in 2015. For the directives-endorsed group (n = 1042), 47% of patients
      received HF in 2011, and 73% received HF in 2015. Conclusions: HF is
      underutilized despite equivalent local control, superior toxicity profile, and
      noninferior late effects. Our study demonstrates the possibility of achieving
      high levels of utilization in a large, multisite, outpatient setting. Factors
      responsible may include default rules established through the development of
      consensus-based treatment directives, peer review by faculty, and strong
      financial leadership to implement HF when indicated. To our knowledge, this is
      the first example of combining both consensus-based treatment directives and
      prospective contouring rounds in an attempt to change practice patterns.

PMID- 30202796
TI  - Clinical outcomes and prognostic factors in patients with stage II-III breast
      cancer treated with neoadjuvant chemotherapy followed by surgery and
      postmastectomy radiation therapy in the modern treatment era.
AB  - Purpose: There are no randomized studies on the indication for postmastectomy
      radiation therapy (PMRT) in patients who receive neoadjuvant chemotherapy (NAC)
      followed by a mastectomy. The aim of this study was to determine clinical
      outcomes and identify reliable prognostic factors in patients with locally
      advanced breast cancer treated with NAC followed by a mastectomy and PMRT.
      Methods and materials: We retrospectively evaluated the relationship between
      clinicopathological factors and outcomes in 351 patients with stage II or III
      breast cancer who underwent NAC followed by radical mastectomy and PMRT between
      March 2005 and December 2013. Results: The median follow-up duration was 81
      months (Range, 12-156 months). For all patients, the 5-year locoregional
      recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and
      overall survival (OS) rates were 91.3 %, 69.8 %, and 83.4 %, respectively. On
      multivariate analysis, estrogen-receptor positivity, and complete response of
      cancer in axillary nodes (ypN0) were significant prognostic factors for better
      LRFS, while lympho-vascular invasion and clinical stage IIIC were independent
      prognostic factors for worse LRFS. The number of axillary node metastasesafter
      surgery was an independent prognostic factor of DMFS and OS. Patients with
      hormone receptor- and human epidermal growth factor receptor 2 positivity had
      significantly better 5-year LRFS rates. Conclusions: We identified several
      prognostic factors in our study. In particular, the number of axillary node
      metastases is significantly related to OS.

PMID- 30202798
TI  - Low-cost optical scanner and 3-dimensional printing technology to create lead
      shielding for radiation therapy of facial skin cancer: First clinical case
      series.
AB  - Purpose: Three-dimensional printing has been implemented at our institution to
      create customized treatment accessories, including lead shields used during
      radiation therapy for facial skin cancer. To effectively use 3-dimensional
      printing, the topography of the patient must first be acquired. We evaluated a
      low-cost, structured-light, 3-dimensional, optical scanner to assess the clinical
      viability of this technology. Methods and materials: For ease of use, the scanner
      was mounted to a simple gantry that guided its motion and maintained an optimum
      distance between the scanner and the object. To characterize the spatial accuracy
      of the scanner, we used a geometric phantom and an anthropomorphic head phantom.
      The geometric phantom was machined from plastic and included hemispherical and
      tetrahedral protrusions that were roughly the dimensions of an average forehead
      and nose, respectively. Polygon meshes acquired by the optical scanner were
      compared with meshes generated from high-resolution computed tomography images.
      Most optical scans contained minor artifacts. Using an algorithm that calculated
      the distances between the 2 meshes, we found that most of the optical scanner
      measurements agreed with those from the computed tomography scanner within
      approximately 1 mm for the geometric phantom and approximately 2 mm for the head
      phantom. We used this optical scanner along with 3-dimensional printer technology
      to create custom lead shields for 10 patients receiving orthovoltage treatments
      of nonmelanoma skin cancers of the face. Patient, tumor, and treatment data were
      documented. Results: Lead shields created using this approach were accurate,
      fitting the contours of each patient's face. This process added to patient
      convenience and addressed potential claustrophobia and medical inability to lie
      supine. Conclusions: The scanner was found to be clinically acceptable, and we
      suggest that the use of an optical scanner and 3-dimensional printer technology
      become the new standard of care to generate lead shielding for orthovoltage
      radiation therapy of nonmelanoma facial skin cancer.

PMID- 30202797
TI  - Adjuvant treatment of meningioma with stereotactic radiation surgery and
      hypofractionated stereotactic radiation surgery: Patterns of care and survival in
      a large, hospital database.
AB  - Objectives: Stereotactic radiation surgery (SRS) and hypofractionated
      stereotactic radiation surgery (HF-SRS) have become an alternative to external
      beam radiation therapy (EBRT) in the adjuvant treatment of meningiomas. The
      purpose of this study was to identify national treatment patterns and survival
      outcomes for meningiomas on the basis of radiation treatment modality in the
      adjuvant setting. Methods and materials: The National Cancer Database was queried
      for patients with meningioma diagnosed between 2010 and 2012. World Health
      Organization grade I disease with subtotal resection and all cases of grade II
      disease regardless of the extent of the resection were included. Logistic
      regression was used to determine factors that were associated with receipt of
      SRS/HF-SRS compared with EBRT. Cox regression was used to determine covariables
      associated with differences in overall survival (OS). Results: A total of 802
      patients met the inclusion criteria of which 173 patients received SRS/HF-SRS
      (22%) and 629 patients (78%) received EBRT. The 3-year OS rate was 97.3% for the
      SRS/HF-SRS group and 93.4% for the EBRT group (P = .018). On subgroup analysis by
      grade, for grade I the 3-year OS rate was 98.3% for the SRS/HF-SRS group versus
      96.7% for the EBRT group (P = .117). For grade II disease, the 3-year OS rate was
      94.4% in the SRS/HF-SRS group versus 92.4% in the EBRT group (P = .199). On
      multivariable analysis, World Health Organization grade II histology (odds ratio
      [OR]: 0.34; 95% confidence interval [CI], 0.21-0.56; P < .001) and gross total
      resection (OR: 0.29; 95% CI, 0.15-0.57; P < .001) were associated with a
      decreased likelihood of receiving SRS/HF-SRS but private insurance (OR: 8.89; 95%
      CI, 1.15-68.47; P = .036) and Medicare (OR: 10.03; 95% CI, 1.28-78.69; P = .028)
      were associated with an increased likelihood of receiving SRS/HF-SRS. Year of
      diagnosis was not associated with receipt of SRS/HF-SRS. The multivariable Cox
      regression demonstrated a trend toward improved OS for treatment with SRS/HF-SRS
      (hazard ratio: 0.24; 95% CI, 0.06-1.03; P = .055). Conclusions: SRS and HF-SRS
      are associated with similar survival as EBRT; however, SRS/HF-SRS is used
      infrequently and usage has not increased over time.

PMID- 30202799
TI  - The role of bone marrow and spleen irradiation in the development of acute
      hematologic toxicity during chemoradiation for esophageal cancer.
AB  - Purpose: The purpose of this study was to determine the impact of splenic and
      thoracic bone marrow irradiation on hematologic toxicity in the setting of
      chemoradiation therapy for esophageal cancer. Methods and materials: We analyzed
      60 patients with carcinoma of the distal esophagus or gastroesophageal junction
      who received concurrent chemoradiation in the preoperative or definitive setting.
      Dosimetric and volumetric parameters were calculated for the spleen, thoracic
      spine, and posterior ribs. The primary endpoint was grade >=3 hematologic
      toxicity (HT3+). Associations were assessed using logistic and linear regression
      models. Results: Twenty-one patients (35%) experienced HT3+, including 18
      patients with leukopenia and 5 with thrombocytopenia. Higher spleen V5-V20 was
      correlated with a lower risk of HT3+ on multivariable analysis (odds ratio: 0.83
      per 10 cm3 increase in V10; P = .013). A dose-dependent decrease in spleen volume
      was observed after radiation therapy, and a greater decrease was independently
      associated with a lower risk of HT3+ (odds ratio: 0.93 per 1% volume decrease; P
      = .014). Dosimetric parameters of the thoracic spine were not significantly
      associated with HT3+. Conclusions: A greater decrease in spleen size after
      radiation therapy and a higher spleen V5-V20 were independently associated with a
      lower risk of severe hematologic toxicity. Splenic irradiation may mitigate
      leukopenia associated with chemoradiation therapy.

PMID- 30202800
TI  - Initial experience with intensity modulated proton therapy for intact, clinically
      localized pancreas cancer: Clinical implementation, dosimetric analysis, acute
      treatment-related adverse events, and patient-reported outcomes.
AB  - Purpose: Pencil-beam scanning intensity modulated proton therapy (IMPT) may allow
      for an improvement in the therapeutic ratio compared with conventional techniques
      of radiation therapy delivery for pancreatic cancer. The purpose of this study
      was to describe the clinical implementation of IMPT for intact and clinically
      localized pancreatic cancer, perform a matched dosimetric comparison with
      volumetric modulated arc therapy (VMAT), and report acute adverse event (AE)
      rates and patient-reported outcomes (PROs) of health-related quality of life.
      Methods and materials: Between July 2016 and March 2017, 13 patients with
      localized pancreatic cancer underwent concurrent capecitabine or 5-fluorouracil
      based chemoradiation therapy (CRT) utilizing IMPT to a dose of 50 Gy
      (radiobiological effectiveness: 1.1). A VMAT plan was generated for each patient
      to use for dosimetric comparison. Patients were assessed prospectively for AEs
      and completed PRO questionnaires utilizing the Functional Assessment of Cancer
      Therapy-Hepatobiliary at baseline and upon completion of CRT. Results: There was
      no difference in mean target coverage between IMPT and VMAT (P > .05). IMPT
      offered significant reductions in dose to organs at risk, including the small
      bowel, duodenum, stomach, large bowel, liver, and kidneys (P < .05). All patients
      completed treatment without radiation therapy breaks. The median weight loss
      during treatment was 1.6 kg (range, 0.1-5.7 kg). No patients experienced grade
      >=3 treatment-related AEs. The median Functional Assessment of Cancer Therapy
      Hepatobiliary scores prior to versus at the end of CRT were 142 (range, 113-163)
      versus 136 (range, 107-173; P = .18). Conclusions: Pencil-beam scanning IMPT was
      feasible and offered significant reductions in radiation exposure to multiple
      gastrointestinal organs at risk. IMPT was associated with no grade >=3
      gastrointestinal AEs and no change in baseline PROs, but the conclusions are
      limited due to the patient sample size. Further clinical studies are warranted to
      evaluate whether these dosimetric advantages translate into clinically meaningful
      benefits.

PMID- 30202801
TI  - Initial toxicity, quality-of-life outcomes, and dosimetric impact in a randomized
      phase 3 trial of hypofractionated versus standard fractionated proton therapy for
      low-risk prostate cancer.
AB  - Purpose: Randomized evidence for extreme hypofractionation in prostate cancer is
      lacking. We aimed to identify differences in toxicity and quality-of-life
      outcomes between standard fractionation and extreme hypofractionated radiation in
      a phase 3 randomized trial. Methods and materials: We analyzed the results of the
      first 75 patients in our phase 3 trial, comparing 38 Gy relative biologic
      effectiveness (RBE) in 5 fractions (n = 46) versus 79.2 Gy RBE in 44 fractions (n
      = 29). Patients received proton radiation using fiducials and daily image
      guidance. We evaluated American Urological Association Symptom Index (AUASI),
      adverse events (AEs), and Expanded Prostate Index Composite (EPIC) domains. The
      primary endpoint of this interim analysis was the cumulative incidence of grade 2
      (G2) or higher AEs. The randomized patient allocation scheme was a 2:1 ratio
      favoring the 38 Gy RBE arm. Results: The median follow-up was 36 months; 30% of
      patients reached 48-month follow-up. AUASI scores differed <5 points (4.4 vs 8.6;
      P = .002) at 1 year, favoring the 79.2 Gy arm. Differences in AUASI were not
      significant at >=18 months. EPIC urinary symptoms favored the 79.2 Gy arm at 1
      year (92.3 vs 84.5; P = .009) and 18 months (92.3 vs 85.3; P = .03); bother
      scores were not significant at other time points. Cumulative >=G2 genitourinary
      toxicity was similar between the 79.2 Gy and 38 Gy arms (34.5% vs 30.4%; P =
      .80). We found no differences in the EPIC domains of bowel symptoms, sexual
      symptoms, or bowel >=G2 toxicities. Bladder V80 (79.2 Gy arm; P = .04) and V39
      (38 Gy arm; P = .05) were predictive for cumulative G2 genitourinary AEs.
      Conclusions: Low AE rates were seen in both study arms. Early temporary
      differences in genitourinary scores disappeared over time. Bladder constraints
      were associated with genitourinary AEs.

PMID- 30202802
TI  - Radiomics-guided therapy for bladder cancer: Using an optimal biomarker approach
      to determine extent of bladder cancer invasion from t2-weighted magnetic
      resonance images.
AB  - Background: Current clinical staging methods are unable to accurately define the
      extent of invasion of localized bladder cancer, which affects the proper use of
      systemic therapy, surgery, and radiation. Our purpose was to test a novel
      radiomics approach to identify optimal imaging biomarkers from T2-weighted
      magnetic resonance imaging (MRI) scans that accurately classify localized bladder
      cancer into 2 tumor stage groups (<=T2 vs >T2) at both the patient level and
      within bladder subsectors. Method and Materials: Preoperative T2-weighted MRI
      scans of 65 consecutive patients followed by radical cystectomy were identified.
      A 3-layer, shell-like volume of interest (VOI) was defined on each MRI slice:
      Inner (lumen), middle (bladder wall), and outer (perivesical tissue). An optimal
      biomarker method was used to identify features from 15,834 intensity and texture
      properties that maximized the classification of patients into <=T2 versus >T2
      groups. A leave-one-out strategy was used to cross-validate the performance of
      the identified biomarker feature set at the patient level. The performance of the
      feature set was then evaluated at the subsector level of the bladder by dividing
      the VOIs into 8 radial sectors. Results: A total of 9 optimal biomarker features
      were derived and demonstrated a sensitivity, specificity, accuracy of prediction,
      and area under a receiver operating characteristic curve of 0.742, 0.824, 0.785,
      and 0.806, respectively, at the patient level and 0.681, 0.788, 0.763, and 0.813,
      respectively, at the radial sector level. All 9 selected features were extracted
      from the middle shell of the VOI and based on texture properties. Conclusions: An
      approach to select a small, highly independent feature set that is derived from
      T2-weighted MRI scans that separate patients with bladder cancer into <=T2 versus
      >T2 groups at both the patient level and within subsectors of the bladder has
      been developed and tested. With external validation, this radiomics approach
      could improve the clinical staging of bladder cancer and optimize therapeutic
      management.

PMID- 30202803
TI  - Late toxicity after post-prostatectomy intensity modulated radiation therapy:
      Evaluating normal-tissue sparing guidelines.
AB  - Purpose: Dose-volume histogram (DVH) toxicity relationships are poorly defined in
      men who receive radiation after radical prostatectomy (RP). We evaluated
      Radiation Therapy Oncology Group (RTOG) study 0534 and institutional intact
      normal-tissue sparing guidelines, as well as dose to bladder trigone, for ability
      to minimize late toxicity. Methods and materials: 164 men received intensity
      modulated radiation therapy (RT) to a median prostate bed dose of 66.6 Gy at a
      median of 22 months after RP. 46% of men were prescribed androgen deprivation
      therapy and pelvic lymph node irradiation to a median dose of 50.4 Gy. DVH
      relationships for the rectum, bladder, trigone, and bladder excluding the
      clinical target volume (bladder-CTV) were analyzed against the Common Terminology
      Criteria for Adverse Events late grade 2 + (G2+) gastrointestinal (GI) and
      genitourinary (GU) toxicity by log-rank test. RTOG 0534 (rectum V65, 40 Gy <=35,
      55%, and bladder-CTV V65, 40 <=50, 70%) and intact prostate RT institutional
      guidelines (rectum V70, 65, 40 <=20, 40, 80% and bladder V70, 65, 40 <=30, 60,
      80%, respectively) guidelines were evaluated. Results: With a median follow-up
      time of of 33 months, the 4-year freedom from G2 + GI and GU toxicity were both
      91%. G2 + GI (n = 12) and GU (n = 15) toxicity included 4% diarrhea (n = 6), 4%
      hemorrhage (n = 6), 1% proctitis (n = 1), and 4% urinary frequency (n = 7), 1%
      obstructive (n = 2), 2% cystitis (n = 3), and 3% incontinence (n = 5),
      respectively. RTOG 0534 rectum and bladder goals were not achieved in 65% and 41%
      of cases, while the institutional intact prostate goals were not achieved in 21%
      and 25% of cases, respectively. Neither dose to the bladder trigone nor any of
      the proposed normal tissue goals were associated with late toxicity (P > .1). In
      the univariate analysis, age, pelvic RT, RT dose, anticoagulation use, androgen
      deprivation therapy, time from RP to RT, and tobacco history were not associated
      with toxicity. Conclusions: More than 90% of men were free from late G2 +
      toxicity 4 years after post-RP intensity modulated RT. No tested parameters were
      associated with late toxicity. In the absence of established normal-tissue DVH
      guidelines in the postoperative setting, the use of intact guidelines is
      reasonable.

PMID- 30202804
TI  - Quantitative clinical outcomes of therapy for head and neck lymphedema.
AB  - Purpose: Head and neck surgery and radiation cause tissue fibrosis that leads to
      functional limitations and lymphedema. The objective of this study was to
      determine whether lymphedema therapy after surgery and radiation for head and
      neck cancer decreases neck circumference, increases cervical range of motion, and
      improves pain scores. Methods and materials: A retrospective review of all
      patients with squamous cell carcinoma of the oral cavity, oropharynx, or larynx
      who were treated with high-dose radiation therapy at a single center between 2011
      and 2012 was performed. Patients received definitive or postoperative radiation
      for squamous cell carcinoma of the oral cavity, oropharynx, or larynx. Patients
      were referred to a single, certified, lymphedema therapist with specialty
      training in head and neck cancer after completion of radiation treatment and
      healing of acute toxicity (typically 1-3 months). Patients underwent at least 3
      months of manual lymphatic decongestion and skilled fibrotic techniques.
      Circumferential neck measurements and cervical range of motion were measured
      clinically at 1, 3, 6, 9, and 12 months after completion of radiation therapy.
      Pain scores were also recorded. Results: Thirty-four consecutive patients were
      eligible and underwent a median of 6 months of lymphedema therapy (Range, 3-12
      months). Clinically measured total neck circumference decreased in all patients
      with 1 month of treatment. Cervical rotation increased by 30.2% on the left and
      27.9% on the right at 1 month and continued to improve up to 44.6% and 55.3%,
      respectively, at 12 months. Patients undergoing therapy had improved pain scores
      from 4.3 at baseline to 2.0 after 1 month. Conclusions: Lymphedema therapy is
      associated with objective improvements in range of motion, neck circumference,
      and pain scores in the majority of patients.

PMID- 30202805
TI  - Using benchmarked lung radiation dose constraints to predict pneumonitis risk:
      Developing a nomogram for patients with mediastinal lymphoma.
AB  - Purpose: We identified lung dosimetric constraints to assist in predicting the
      radiation pneumonitis (RP) risk in patients with mediastinal lymphoma and then
      identified the clinical prognostic factors that were associated with the
      achievement of key dosimetric constraints. Methods and Materials: In 190 patients
      who received mediastinal intensity modulated radiation therapy, we used
      univariate chi2 and multivariate logistic models to identify the predictors of RP
      and achievement of lung dose-volume histogram (DVH) constraints and build a
      predictive nomogram for RP. Results: An increased risk of RP was strongly
      associated with mean lung dose (MLD) > 13.5 Gy (odds ratio [OR]: 8.13; 95%
      confidence interval [CI], 3.01-21.93; P < .001) and the percent of lung volume
      receiving >=5 Gy (V5) > 55% (OR: 7.01; 95% CI, 2.94-16.72; P < .001). Therefore,
      patients had low RP risk (8%) if both MLD <=13.5 and V5 <=55 constraints were
      achieved, moderate risk (24%) if only MLD was achieved, and the highest risk
      (48%) if MLD was not achieved. Deep-inspiration breath-hold (DIBH) technique
      during treatment strongly prognosticated achieving MLD and V5 DVH constraints
      (OR,3.88; 95% CI, 1.84-8.19; P < .001). Specifically, 86% of patients who were
      treated with DIBH versus 63% without DIBH achieved DVH constraints (P < .001).
      This translated into a "number needed to treat" with DIBH of 4 patients to enable
      1 additional patient to achieve both constraints. In comparison, the clinical
      characteristics were marginal prognosticators: DVH constraints were more likely
      achieved in nonbulky disease (OR: 3.01; 95% CI, 0.89-4.53; P = .09) and patients
      who had not previously received salvage chemotherapy (OR, 2.44; 95% CI, 0.98
      6.11; P = .06). Nomogram-predicted risks of RP ranged from 4% to 60% on the basis
      of MLD and V5, total radiation dose, and use of salvage chemotherapy.
      Conclusions: Achieving mean lung and V5 DVH constraints is critical to reduce RP
      risk in patients with lymphoma who receive mediastinal intensity modulated
      radiation therapy. The use of the DIBH technique is a promising risk-modifying
      treatment approach in patients with mediastinal lymphoma and especially in
      patients with a history of nonmodifiable risk factors for RP such as bulky
      disease and salvage chemotherapy.

PMID- 30202806
TI  - Palliative radiation and fractionation in medicare patients with incurable non
      small cell lung cancer.
AB  - Purpose: Palliative radiation therapy (RT) can improve quality of life but also
      incurs time and financial costs. The aim of this study was to evaluate factors
      associated with use and intensity of palliative RT for incurable non-small cell
      lung cancer (NSCLC). Methods and materials: This was a retrospective analysis of
      Medicare's Surveillance, Epidemiology and End Results data. We identified
      patients who were diagnosed with incurable (American Joint Committee on Cancer
      6th edition stage IIIB with malignant effusion or stage IV) NSCLC between 2004
      and 2011. Univariable and multivariable logistic regressions were used to
      identify factors associated with the receipt of palliative RT and the use of >10
      fractions during the first course of radiation. Among patients who were treated
      with radiation, freestanding versus hospital-based center information was
      collected on the basis of the location of the RT delivery claim. Results: Among
      55,258 patients with incurable NSCLC, 38% (21,053 patients) received palliative
      RT during the first year after diagnosis. Among patients who received RT, 56%
      (11,717 patients) received >10 fractions. On multivariable analysis, factors
      associated with greater RT use included younger age group (overall P < .01),
      lower modified Charlson comorbidity score (overall P < .01), female sex (odds
      ratio [OR]: 1.1; P < .01), marital status (OR: 1.1; P < .01), and chemotherapy
      use (OR: 3.6; P < .01). Predictors for >10 fractions were chemotherapy use (OR:
      1.7; P < .01) and treatment at a freestanding versus hospital-based facility (58%
      vs 43%; OR: 1.7; P < .01). Conclusions: More than a third of patients diagnosed
      with incurable lung cancer receive palliative RT and 56% received >10 fractions.
      The use of RT varied by region and patient characteristics, and patients treated
      at freestanding RT centers were more likely to receive >10 fractions. Further
      research into factors that influence treatment decisions including potential
      financial incentives may contribute to the high value and strategic utilization
      of palliative RT.

PMID- 30202807
TI  - Safety of combining thoracic radiation therapy with concurrent versus sequential
      immune checkpoint inhibition.
AB  - Purpose: The objective of this study was to evaluate adverse events (AEs) in
      patients who received both immune checkpoint inhibitors and thoracic radiation
      therapy (RT). In particular, we compared the rate of toxicities of concurrent
      versus sequential delivery of thoracic RT and checkpoint inhibitors. Methods and
      Materials: Patient and treatment characteristics were collected on all patients
      at our institution who were treated with programmed cell death protein 1 (PD-1),
      programmed death-ligand 1 (PD-L1), and/or cytotoxic T-lymphocyte-associated
      protein 4 (CTLA-4) inhibitors and underwent thoracic RT (n = 79). Receiving both
      treatments within 1 month was considered concurrent (n = 35; 44%), and any
      treatment up to 6 months apart was considered sequential (n = 44; 56%). The
      primary endpoint of this study was the rate of Grade >=2 AEs from combination
      therapy (immunotherapy and RT), specifically those that are relevant to thoracic
      RT: Pneumonitis, other pulmonary events, esophagitis, dermatitis, and fatigue.
      Further univariate analysis was performed to compare AE rates with clinical and
      therapy-related variables. Results: A total of 79 patients were identified, with
      lung cancer (n = 45) and melanoma (n = 15) being the most common primary
      histology. Sixty-two (78%) patients were treated with anti-PD-1 or anti-PD-L1
      antibodies, 12 (15%) with anti-CTLA-4 antibodies, and 5 (6%) received both anti
      PD-1/PD-L1 and anti-CTLA-4 antibodies. The median follow-up for survivors was 5.9
      months (range, 2.4-55.6 months). Grade >=2 AEs included pneumonitis (n = 5; 6%),
      esophagitis (n = 6; 8%), and dermatitis (n = 8; 10%). No statistically
      significant correlation was found between these AEs when comparing concurrent
      versus sequential treatment. The only significant variable was a correlation of
      immunotherapy drug category with Grade >=2 esophagitis (P = .04). Conclusions:
      Overall, Grade >=2 AE rates of thoracic RT and immunotherapy appeared as expected
      and acceptable. The lack of significant differences in AE rates with concurrent
      versus sequential treatment suggests that even concurrent immunotherapy and
      thoracic RT may be safe.

PMID- 30202808
TI  - Multi-institutional report on toxicities of concurrent nivolumab and radiation
      therapy.
AB  - Purpose: Radiation therapy (RT) and nivolumab are standard therapies for a wide
      range of advanced and metastatic cancers, yet little is known about the toxicity
      profile of their combined treatment. The rate of grade >=3 toxicities from
      nivolumab monotherapy and radiation-only palliative treatments has been reported
      at 10% to 18% and 0% to 26%, respectively. We reviewed our experience to assess
      the acute toxicity profile of concurrent RT-nivolumab. Methods and materials: A
      retrospective review of all consecutive patients from January 2015 to May 2017
      who received concurrent RT-nivolumab was conducted at 4 separate centers.
      Concurrent RT-nivolumab was defined as RT completed between 3 days prior to
      initial nivolumab infusion and 28 days after the last nivolumab infusion.
      Results: Of the 261 patients who received nivolumab, 46 (17.6%) had concurrent RT
      to 67 treatment sites. The median follow-up was 3.3 months (interquartile range,
      1.7-6.1 months) and the 1-year overall survival rate was 22%. For the 11 of 46
      patients (24%) who were alive at last analysis, the median follow-up was 12.8
      months (interquartile range, 8.3-14.9 months). The most common histology, RT
      prescription, and treatment site were non-small cell lung cancer (23 of 46
      patients; 50%), 30 Gy in 10 fractions (24 of 67 patients; 35.8%), and
      abdomen/pelvis (16 of 67 patients; 24%), respectively. Four patients with
      melanoma had concurrent ipilimumab and were removed from the final toxicity
      analysis of RT-nivolumab. Within 3 months of treatment with RT-nivolumab, 4 of 42
      patients (9.5%) experienced grade 3 toxicity and 2 of these patients' toxicities
      were attributed specifically to the addition of RT: grade 3 hearing loss after
      whole brain RT and grade 3 pancreatitis after stereotactic body RT to the left
      adrenal gland. One death from transaminitis was attributed to nivolumab alone
      because the RT field did not encompass the liver. Conclusions: Concurrent RT
      nivolumab did not appear to increase the toxicity profile from the previously
      reported toxicity rates from nivolumab or radiation alone.

PMID- 30202809
TI  - Risk factors for late bowel and bladder toxicities in NRG Oncology prostate
      cancer trials of high-risk patients: A meta-analysis of physician-rated
      toxicities.
AB  - Purpose: A meta-analysis of sociodemographic variables and their association with
      late (>180 days from start of radiation therapy[RT]) bowel, bladder, and
      clustered bowel and bladder toxicities was conducted in patients with high-risk
      (clinical stages T2c-T4b or Gleason score 8-10 or prostate-specific antigen level
      >20) prostate cancer. Methods and materials: Three NRG trials (RTOG 9202, RTOG
      9413, and RTOG 9406) that accrued from 1992 to 2000 were used. Late toxicities
      were measured with the Radiation Therapy Oncology Group Late Radiation Morbidity
      Scale. After controlling for study, age, Karnofsky Performance Status, and year
      of accrual, sociodemographic variables were added to the model for each outcome
      variable of interest in a stepwise fashion using the Fine-Gray regression models
      with an entry criterion of 0.05. Results: A total of 2432 patients were analyzed
      of whom most were Caucasian (76%), had a KPS score of 90 to 100 (92%), and
      received whole-pelvic RT+HT (67%). Of these patients, 13 % and 16% experienced
      late grade >=2 bowel and bladder toxicities, respectively, and 2% and 3%
      experienced late grade >=3 bowel and bladder toxicities, respectively. Late grade
      >=2 clustered bowel and bladder toxicities were seen in approximately 1% of
      patients and late grade >=3 clustered toxicities were seen in 2 patients (<1%).
      The multivariate analysis showed that patients who received prostate-only RT+HT
      had a lower risk of experiencing grade >=2 bowel toxicities than those who
      received whole-pelvic RT+long-term (LT) HT (hazard ratio: 0.36; 95% confidence
      interval, 0.18-0.73; P = .0046 and hazard ratio: 0.43; 95% confidence interval,
      0.23-0.80; P = .008, respectively). Patients who received whole-pelvic RT had
      similar chances of having grade >=2 bowel or bladder toxicities no matter whether
      they received LT or short-term HT. Conclusions: Patients with high-risk prostate
      cancer who receive whole-pelvic RT+LT HT are more likely to have a grade >=2
      bowel toxicity than those who receive prostate-only RT. LT bowel and bladder
      toxicities were infrequent. Future studies will need to confirm these findings
      utilizing current radiation technology and patient-reported outcomes.

PMID- 30202810
TI  - Model evaluation of rapid 4-dimensional lung tomosynthesis.
AB  - Purpose: This is an investigation of a lung motion digital tomosynthesis (DTS)
      model using combined stationary detector and stationary cold cathode x-ray
      sources at projection acquisition rates that exceed the present norms. The intent
      is to reduce anatomical uncertainties from artifacts inherent in thoracic 4
      dimensional computed tomography (CT). Methods and materials: Parameters necessary
      to perform rapid lung 4-dimensional DTS were studied using a conventional
      radiographic system with linear motion of the x-ray source and a simple
      hypothetical hardware performance model. Hypothetical rapid imaging parameters of
      sweep duration, projections per second, pulse duration, and tube current (mA)
      were derived on the basis of 0.5 mm and 1 mm motion captures per phase, 10 and 15
      breaths per minute (bpm), 10 to 40 mm breathing amplitude, and 2 signal-to-noise
      ratio (SNR) levels. Anterior-posterior and lateral projection images of a normal
      size anthropomorphic thorax phantom with iodine contrast inserts were collected
      and reconstructed with an algebraic algorithm to study the effects of reduced x
      ray output associated with field emission cold cathodes composed of carbon
      nanotubes or metal Spindt-type. Radiographic projections were collected at 3 SNR
      levels that were set at standard clinical DTS milliampere-seconds (mAs) and
      reduced corresponding to 50% and 25% standard DTS mAs to simulate a reduced x-ray
      output. Results: The DTS SNR of the inserts was superior in all reconstructions
      at clinical mAs versus automatic exposure-control radiographs and superior in 3
      of 4 at the 50% and 25% mAs levels. The most demanding performance parameters
      corresponding to 40 mm amplitude, 15 bpm, 0.5 mm motion capture limit, and 61
      projections were sweep duration (10.4 msec), projection rate (5862 projections
      per second), pulse duration (0.161 msec), current 189 mA anterior-posterior, and
      653 mA lateral. Conclusions: Feasibility depends on the output performance of
      stationary cold cathode hardware being developed for DTS. Present image receptor
      technology can accommodate frame acquisition rates.

PMID- 30202811
TI  - Autoradiography and biopsy measurements of a resected hepatocellular carcinoma
      treated with 90 yttrium radioembolization demonstrate large absorbed dose
      heterogeneities.
AB  - Purpose: Radioembolization is an alternative palliative treatment for
      hepatocellular carcinoma. Here, we examine the uptake differences between tumor
      tissue phenotypes and present a cross-section of the absorbed dose throughout a
      liver tissue specimen. Methods and materials: A patient with hepatocellular
      carcinoma was treated with 90Y radioembolization followed by liver tissue
      resection. Gamma camera images and autoradiographs were collected and biopsy
      tissue samples were analyzed using a gamma well counter and light microscopy.
      Results: An analysis of 25 punched biopsy tissue samples identified 4 tissue
      regions: Normal tissue, viable tumor tissue with and without infarcted areas, and
      tumor areas with postnecrotic scar tissue. Autoradiography and biopsy tissue
      sample measurements showed large dose differences between viable and postnecrotic
      tumor tissue (159 Gy vs 23 Gy). Conclusions: Radioembolization of 90 yttrium with
      resin microspheres produces heterogeneous-absorbed dose distributions in the
      treatment of unifocal hepatic malignancies that could not be accurately
      determined with current gamma camera imaging techniques.

PMID- 30202812
TI  - Definitive hypofractionated radiation therapy for early stage breast cancer:
      Dosimetric feasibility of stereotactic ablative radiotherapy and proton beam
      therapy for intact breast tumors.
AB  - Purpose: Few definitive treatment options exist for elderly patients diagnosed
      with early stage breast cancer who are medically inoperable or refuse surgery.
      Historical data suggest very poor local control with hormone therapy alone. We
      examined the dosimetric feasibility of hypofractionated radiation therapy using
      stereotactic ablative radiotherapy (SABR) and proton beam therapy (PBT) as a
      means of definitive treatment for early stage breast cancer. Methods and
      Materials: Fifteen patients with biopsy-proven early stage breast cancer with a
      clinically visible tumor on preoperative computed tomography scans were
      identified. Gross tumor volumes were contoured and correlated with known biopsy
      proven malignancy on prior imaging. Treatment margins were created on the basis
      of set-up uncertainty and image guidance capabilities of the three radiation
      modalities analyzed (3-dimensional conformal radiation therapy [3D-CRT], SABR,
      and PBT) to deliver a total dose of 50 Gy in 5 fractions. Dose volume histograms
      were analyzed and compared between treatment techniques. Results: The median
      planning target volume (PTV) for SABR, PBT, and 3-dimensional CRT was 11.91,
      21.03, and 45.08 cm3, respectively, and were significantly different (P < .0001)
      between treatment modalities. Overall target coverage of gross tumor and clinical
      target volumes was excellent with all three modalities. Both SABR and PBT
      demonstrated significant dosimetric improvements, each in its own unique manner,
      relative to 3D-CRT. Dose constraints to normal structures including
      ipsilateral/contralateral breast, bilateral lungs, and heart were all
      consistently achieved using SABR and PBT. However, skin or chest wall dose
      constraints were exceeded in some cases for both SABR and PBT plans and was
      dictated by the anatomic location of the tumor. Conclusions: Definitive
      hypofractionated radiation therapy using SABR and PBT appears to be
      dosimetrically feasible for the treatment of early stage breast cancer. The
      anatomical location of the tumor relative to the skin and chest wall appears to
      be the primary limiting dosimetric factor.

PMID- 30202813
TI  - Skin recurrence in the radiation treatment of breast cancer.

PMID- 30202814
TI  - Complete response of pleural effusions caused by extramedullary hematopoiesis to
      low-dose, single fraction palliative radiation therapy: Case report and
      literature review.

PMID- 30202815
TI  - Hepatic connexin 32 associates with nonalcoholic fatty liver disease severity.
AB  - Emerging data highlight the critical role for the innate immune system in the
      progression of nonalcoholic fatty liver disease (NAFLD). Connexin 32 (Cx32), the
      primary liver gap junction protein, is capable of modulating hepatic innate
      immune responses and has been studied in dietary animal models of
      steatohepatitis. In this work, we sought to determine the association of hepatic
      Cx32 with the stages of human NAFLD in a histologically characterized cohort of
      362 patients with NAFLD. We also studied the hepatic expression of the genes and
      proteins known to interact with Cx32 (known as the connexome) in patients with
      NAFLD. Last, we used three independent dietary mouse models of nonalcoholic
      steatohepatitis to investigate the role of Cx32 in the development of
      steatohepatitis and fibrosis. In a univariate analysis, we found that Cx32
      hepatic expression associates with each component of the NAFLD activity score and
      fibrosis severity. Multivariate analysis revealed that Cx32 expression most
      closely associated with the NAFLD activity score and fibrosis compared to known
      risk factors for the disease. Furthermore, by analyzing the connexome, we
      identified novel genes related to Cx32 that associate with NAFLD progression.
      Finally, we demonstrated that Cx32 deficiency protects against liver injury,
      inflammation, and fibrosis in three murine models of nonalcoholic steatohepatitis
      by limiting initial diet-induced hepatoxicity and subsequent increases in
      intestinal permeability. Conclusion: Hepatic expression of Cx32 strongly
      associates with steatohepatitis and fibrosis in patients with NAFLD. We also
      identify novel genes associated with NAFLD and suggest that Cx32 plays a role in
      promoting NAFLD development. (Hepatology Communications 2018;2:786-797).

PMID- 30202817
TI  - Whole-Exome Sequencing Study of Extreme Phenotypes of NAFLD.
AB  - Nonalcoholic fatty liver disease (NAFLD) is a heterogeneous disease with highly
      variable outcomes. Patients with simple steatosis typically experience a benign
      course, whereas those with more advanced liver injury, nonalcoholic
      steatohepatitis (NASH), and advanced stage fibrosis suffer increased risk for
      complications such as cirrhosis, hepatic decompensation, and liver cancer.
      Genetic variants in patatin-like phospholipase domain-containing 3 (PNPLA3) and
      transmembrane 6 superfamily member 2 (TM6SF2) and clinical factors including
      diabetes, obesity, and older age increase a patient's risk for NASH, advanced
      fibrosis, and worse outcomes. Despite substantial investigation and
      identification of some common variants associated with NAFLD and advanced
      fibrosis, the genetics and functional mechanisms remain poorly understood. This
      study aimed to identify genetic variants by whole-exome sequencing of NAFLD
      phenotypes to provide novel insights into mechanisms behind NAFLD pathogenesis
      and variability. We sequenced 82 patients with liver biopsy-confirmed NAFLD and
      4455 population controls. NAFLD patients were divided into extreme phenotypes
      based on liver fibrosis stage and clinical risk factors to investigate rare
      variants that might predispose to or protect from advanced NAFLD fibrosis. We
      compared NAFLD extremes to each other and individually to population controls,
      exploring genetic variation at both the single-variant and gene-based level. We
      replicated known associations with PNPLA3 and TM6SF2 and advanced fibrosis,
      despite sample-size limitations. We also observed enrichment of variation in
      distinct genes for progressor or protective NAFLD phenotypes, although these
      genes did not reach statistical significance. Conclusion: We report the first
      whole-exome sequencing study of genetic variation in liver biopsy-confirmed NAFLD
      susceptibility and severity, using a small cohort of extreme NAFLD phenotypes and
      a large cohort of population controls.

PMID- 30202819
TI  - NGM282 for Treatment of Patients With Primary Biliary Cholangitis: A Multicenter,
      Randomized, Double-Blind, Placebo-Controlled Trial.
AB  - Patients with primary biliary cholangitis (PBC) who had an inadequate response to
      ursodiol have few treatment options. Alkaline phosphatase (ALP) and bilirubin
      levels correlate with the risk of liver transplant or death in PBC patients.
      Fibroblast growth factor (FGF) 19 is a hormone that acts directly in the liver to
      regulate bile acid synthesis. We evaluated NGM282, an engineered analogue of
      FGF19, for the treatment of PBC. In this 28-day, double-blind, placebo-controlled
      phase 2 trial, 45 PBC patients who had an inadequate response to ursodiol were
      randomly assigned 1:1:1 to receive subcutaneous daily doses of either NGM282 at
      0.3 mg (n = 14), 3 mg (n = 16), or placebo (n = 15). The primary endpoint was a
      change in ALP from baseline after 28 days of treatment. At day 28, ALP was
      significantly reduced with NGM282 treatment at both 0.3 mg (least-squares mean 
      51.0 IU/L [standard error (SE) 15.4]) and 3 mg (-66.0 IU/L [SE 16.0]) versus
      placebo (3.3 IU/L [SE 14.8]), with least-squares mean differences of -54.3 IU/L
      (95% confidence interval -104.2 to -4.5; P = 0.0149) and -69.3 IU/L (95%
      confidence interval -120.5 to -18.3; P = 0.0030), respectively. Fifty percent (7
      of 14) of patients receiving NGM282 0.3 mg and 46% (6 of 13) of those receiving
      NGM282 3mg achieved 15% or greater reduction in ALP levels from baseline,
      compared with 7% (1 of 15) of patients receiving placebo. NGM282 also
      significantly reduced serum concentrations of transaminases and immunoglobulins.
      Most adverse events were grade 1 (mild) to grade 2 (moderate) in severity, with
      gastrointestinal disorders more frequent in the NGM282 treatment groups. No
      worsening of pruritus was observed with NGM282 treatment. Conclusion: NGM282
      administered for 28 days resulted in significant improvements in ALP and
      transaminase levels compared with placebo, with an acceptable safety profile in
      patients with PBC. (Hepatology Communications 2018; 00:000-000).

PMID- 30202818
TI  - A Rare Nonsense Mutation in the Glucokinase Regulator Gene Is Associated With a
      Rapidly Progressive Clinical Form of Nonalcoholic Steatohepatitis.
AB  - We report on the presence of a rare nonsense mutation (rs149847328, p.Arg227Ter)
      in the glucokinase regulator (GCKR) gene in an adult patient with nonalcoholic
      fatty liver disease (NAFLD), morbid obesity, and type 2 diabetes; this patient
      developed a progressive histological form of the disease. Analysis of paired (5
      years apart) liver biopsies (at baseline and follow-up) showed progression of
      simple steatosis to severe nonalcoholic steatohepatitis and cirrhosis. Study
      design involved an initial exploration that consisted of deep sequencing of 14
      chromosomal regions in 96 individuals (64 of whom were patients with NAFLD who
      were diagnosed by liver biopsy that showed the full spectrum of histological
      severity). We further performed a replication study to explore the presence of
      rs149847328 that included a sample of 517 unrelated individuals in a case-control
      study (n = 390), including patients who were morbidly obese (n = 127).
      Exploration of sequence variation by next-generation sequencing of exons, exon
      intron boundaries, and 5' and 3' untranslated regions of 14 genomic loci that
      encode metabolic enzymes of the tricarboxylic acid cycle revealed the presence of
      heterozygosity for the p.Arg227Ter mutation, the frequency of which is 0.0003963
      (4:10,000; Exome Aggregation Consortium database). GCKR protein expression was
      markedly decreased in the liver of the affected patient compared with patients
      with NAFLD who carry the wild-type allele. Sequencing of the same 14 genomic loci
      in 95 individuals failed to reveal the rare mutation. The rarity of p.Arg227Ter
      was confirmed in a more extensive screening. Conclusion: While rare
      variants/mutations are difficult to detect in even reasonably large samples
      (frequency of the mutant allele of p.Arg227Ter was ~1:1,000 in our data set), the
      presence of this mutation should be suspected as potentially associated with
      NAFLD, particularly in young adults at the extreme of histological phenotypes.
      Hepatology Communications 2018;0:0-0).

PMID- 30202820
TI  - Follicular T Helper Cell Signatures in Primary Biliary Cholangitis and Primary
      Sclerosing Cholangitis.
AB  - Primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) are
      the most common cholestatic liver diseases. While PBC is generally accepted to be
      an autoimmune disorder characterized by pathognomonic autoantibodies against
      mitochondrial antigens, the pathogenesis of PSC is less precisely defined;
      however, some degree of altered immunity toward autoantigens has been suggested.
      Follicular T helper (Tfh) cells, a distinct clusters of differentiation (CD)4 T
      cell subset specialized in facilitating antibody responses, have been shown to
      contribute to humoral autoimmunity in various disorders; yet, there is only
      limited information on possible alterations of Tfh cells in the context of
      cholestatic liver diseases. Thus, we addressed this important question by
      analyzing the frequency, activation status, and function of Tfh cells and
      frequencies of regulatory follicular T helper (Tfr) cells in well-defined cohorts
      of patients with PBC and patients with PSC. Interestingly, we observed a
      significant increase in circulating chemokine (C-X-C motif) receptor 5
      (CXCR5)+programmed death 1 (PD-1) +CD4+ Tfh cells in patients with PBC but not in
      those with PSC. Although the frequency of potentially pathogenic chemokine (C-C
      motif) receptor 7 (CCR7)lowCXCR5+PD-1+CD4+ Tfh cells was increased in both
      disorders compared to healthy donors, the increase was significantly more
      pronounced in PBC. Furthermore, in patients with PBC, Tfh cells displayed
      stronger expression of the activation markers OX40 and inducible costimulator of
      T cells, correlated with anti-anti-mitochondrial antibody M2 and immunoglobulin M
      titers, and were most significantly increased in patients with cirrhosis. Tfr
      cell numbers were similarly increased; however, Tfh/Tfr ratios were unaltered in
      PSC and PBC. These alterations did not correlate with increased secretion of the
      Tfh signature cytokine interleukin-21 in sorted CD4 T cells. Conclusion:
      Significant alterations occur in the Tfh cell compartment in cholestatic liver
      diseases, suggesting that Tfh cells influence the pathogenesis of PBC and to a
      lesser extend PSC.

PMID- 30202816
TI  - High-Mobility Group Box-1 and Liver Disease.
AB  - High-mobility group box-1 (HMGB1) is a ubiquitous protein. While initially
      thought to be simply an architectural protein due to its DNA-binding ability,
      evidence from the last decade suggests that HMGB1 is a key protein participating
      in the pathogenesis of acute liver injury and chronic liver disease. When it is
      passively released or actively secreted after injury, HMGB1 acts as a damage
      associated molecular pattern that communicates injury and inflammation to
      neighboring cells by the receptor for advanced glycation end products or toll
      like receptor 4, among others. In the setting of acute liver injury, HMGB1
      participates in ischemia/reperfusion, sepsis, and drug-induced liver injury. In
      the context of chronic liver disease, it has been implicated in alcoholic liver
      disease, liver fibrosis, nonalcoholic steatohepatitis, and hepatocellular
      carcinoma. Recently, specific posttranslational modifications have been
      identified that could condition the effects of the protein in the liver. Here, we
      provide a detailed review of how HMGB1 signaling participates in acute liver
      injury and chronic liver disease.

PMID- 30202821
TI  - Abundance of Cytochromes in Hepatic Extracellular Vesicles Is Altered by Drugs
      Related With Drug-Induced Liver Injury.
AB  - Drug-induced liver injury (DILI) is a serious worldwide health problem that
      accounts for more than 50% of acute liver failure. There is a great interest in
      clinical diagnosis and pharmaceutical industry to elucidate underlying molecular
      mechanisms and find noninvasive biomarkers for this pathology. Cell-secreted
      extracellular vesicles (EVs) have provided a new biological source to identify
      low disease invasive markers. Despite the intense research developed on these
      vesicles, there is currently a gap on their patho-physiological effects. Here, we
      study EVs secreted by primary rat hepatocytes challenged with galactatosamine
      (GalN), acetaminophen, or diclofenac as DILI in vitromodels. Proteomics analysis
      of these EVs revealed an increase in enzymes already associated with liver
      damage, such as catecholamine-methyl transferase and arginase 1. An increase in
      translation-related proteins and a decrease in regulators of apoptosis were also
      observed. In addition, we show the presence of enzymatic activity of P450
      cytochrome 2d1 in EVs. The activity specifically is decreased in EVs secreted by
      hepatocytes after acetaminophen treatment and increased in EVs derived from GalN
      treated hepatocytes. By using in vivo preclinical models, we demonstrate the
      presence of this cytochrome activity in circulation under normal conditions and
      an increased activity after GalN-induced injury. Conclusion: Hepatocyte-secreted
      EVs carry active xenobiotic-metabolizing enzymes that might be relevant in
      extracellular metabolism of drugs and be associated with DILI. (Hepatology
      Communications 2018;0:00-00).

PMID- 30202822
TI  - Dipeptidyl Peptidase-4 Is a Pro-Recovery Mediator During Acute Hepatotoxic Damage
      and Mirrors Severe Shifts in Kupffer Cells.
AB  - Dipeptidyl peptidase-4 (DPP-4 or clusters of differentiation [CD]26) is a
      multifunctional molecule with established roles in metabolism. Pharmacologic
      inhibition of DPP-4 is widely used to improve glycemic control through regulation
      of the incretin effect. Colaterally, CD26/DPP-4 inhibition appears to be
      beneficial in many inflammatory conditions, namely in delaying progression of
      liver pathology. Nevertheless, the exact implications of CD26/DPP-4 enzymatic
      activity in liver dysfunction remain unclear. In this work, we investigated the
      involvement of CD26/DPP-4 in experimental mouse models of induced hepatocyte
      damage that severely impact Kupffer cell (KC) populations. Liver dysfunction was
      evaluated in CD26 knockout (KO) and B6 wild-type mice during acute liver damage
      induced by acetaminophen, chronic liver damage induced by carbon tetrachloride,
      and KC-depleting treatment with clodronate-loaded liposomes. We found that
      necrosis resolution after hepatotoxic injury was delayed in CD26KO mice and in B6
      mice treated with the CD26/DPP-4 inhibitor sitagliptin, suggesting that DPP-4
      enzymatic activity plays a role in recovering from acute liver damage.
      Interestingly, the severe KC population reduction in acute and chronic liver
      injury was concomitant with increased CD26/DPP-4 serum levels. Remarkably, both
      chronic liver damage and noninflammatory depletion of KCs by clodronate liposomes
      were marked by oscillation in CD26/DPP-4 serum activity that mirrored the
      kinetics of liver KC depletion/recovery. Conclusion:CD26/DPP-4 enzymatic activity
      contributes to necrosis resolution during recovery from acute liver injury. Serum
      CD26/DPP-4 is elevated when severe perturbations are imposed on KC populations,
      regardless of patent liver damage. We propose that serum CD26/DPP-4 is a
      potential systemic surrogate marker of severe impairments in the KC population
      imposed by clinical and subclinical liver conditions.

PMID- 30202823
TI  - Suboptimal Level of Bone-Forming Cells in Advanced Cirrhosis are Associated with
      Hepatic Osteodystrophy.
AB  - Bone loss is common in advanced cirrhosis, although the precise mechanisms
      underlying bone loss in cirrhosis are unknown. We studied the profile and
      functionality of bone-forming cells and bone-building proteins in bone marrow
      (BM) of individuals with cirrhosis (n = 61) and individuals without cirrhosis as
      normal controls (n = 50). We also performed dual energy X-ray absorptiometry for
      clinical correlation. BM mesenchymal cells (MSCs) were analyzed for colony
      forming units-fibroblasts and their osteogenic (fibronectin-1 [FN1], insulin-like
      growth factor binding protein 3 [IGFBP3], collagen type 1 alpha 1 chain [COL1A1],
      runt-related transcription factor 2 [RUNX2], and alkaline phosphatase, liver
      [ALPL]) and adipogenic ( adiponectin, C1Q, and collagen domain containing
      [ADIPOQ], peroxisome proliferator-activated receptor gamma [PPARgamma], and fatty
      acid binding protein 4 [FABP4]) potentials. Colony-forming units-fibroblasts were
      lower in patients with cirrhosis (P = 0.002) than in controls. Cirrhotic BM-MSCs
      showed >2-fold decrease in osteogenic markers. Compared to controls, patients
      with cirrhosis showed fewer osteocytes (P = 0.05), osteoblasts, chondroblasts,
      osteocalcin-positive (osteocalcin+) area, clusters of differentiation (CD)169+
      macrophages (P < 0.001, each), and nestin+ MSCs (P = 0.001); this was more
      apparent in Child-Turcotte-Pugh (CTP) class C than A (P < 0.001). Multivariate
      logistic regression showed low nestin+ MSCs (P = 0.004) as a predictor of bone
      loss. Bone-resolving osteoclasts were comparable among CTP groups, but >2-fold
      decreased anti-osteoclastic and increased pro-osteoclastic factors were noted in
      patients with CTP C compared to CTP A. Bone-building proteins (osteocalcin [P =
      0.008], osteonectin [P < 0.001], and bone morphogenic protein 2 [P = 0.001]) were
      decreased while anti-bone repair factors (fibroblast growth factor 23 [P = 0.015]
      and dipeptidyl peptidase 4 [P < 0.001]) were increased in BM and peripheral
      blood; this was more apparent in advanced cirrhosis. The dual energy X-ray
      absorptiometry scan T score significantly correlated with the population of
      osteoblasts, osteocytes, MSCs, and CD169+ macrophages. Conclusion:
      Osteoprogenitor cells are substantially reduced in patients with cirrhosis and
      more so in advanced disease. Additionally, increased anti-bone repair proteins
      enhance the ineffective bone repair and development of osteoporosis in cirrhosis.
      Hepatology Communications 2018;0:0-0).

PMID- 30202824
TI  - Serum Autotaxin Concentrations Reflect Changes in Liver Stiffness and Fibrosis
      After Antiviral Therapy in Patients with Chronic Hepatitis C.
AB  - The purpose of this study was to determine whether serum autotaxin concentrations
      reflect liver stiffness in patients with chronic hepatitis C virus (HCV) treated
      with direct-acting antiviral agents. Adult patients with chronic HCV were
      enrolled from January 2016 to August 2017. Autotaxin concentrations in these
      patients were compared with those of a control group consisting of healthy
      individuals. Liver stiffness was determined by transient elastography. The
      relationship between fibrosis markers and fibrosis scores was evaluated before
      and after treatment. Data from 155 HCV patients and 56 control subjects were
      analyzed. Autotaxin concentrations were significantly higher in HCV patients with
      liver stiffness scores less than or equal to 7.4 kPa versus controls. Autotaxin
      concentrations at the end of treatment and beyond were significantly lower than
      those prior to treatment. Pretreatment and posttreatment autotaxin concentrations
      in male and female patients with liver stiffness scores greater than 14.9 kPa
      changed significantly (P < 0.01 and P < 0.01, respectively). From the start of
      treatment to 6 months following treatment, the fibrosis marker/liver stiffness
      score ratios changed as follows: autotaxin: 0.189 (95% confidence interval [CI]:
      0.169-0.209) to 0.191 (95% CI: 0.166-0.216; P= 0.88); Wisteria
      floribundaagglutinin-positive Mac-2-binding protein: 0.294 (95% CI: 0.256-0.332)
      to 0.223 (95% CI: 0.191-0.255; P< 0.001); hyaluronic acid: 19.05 (95% CI: 14.29
      23.81) to 13.92 (95% CI: 11.16-16.70; P = 0.044); and type IV collagen 7S: 0.560
      (95% CI: 0.515-0.604) to 0.546 (95% CI: 0.497-0.895; P = 0.052). Conclusion:
      Autotaxin concentrations reflect liver stiffness before and after antiviral
      treatment in patients with chronic HCV infection.

PMID- 30202825
TI  - Discovery of the Novel Entecavir-Resistant Hepatitis B Virus Reverse
      Transcriptase A181C Substitution From an Integrated Genotypic Analysis.
AB  - Entecavir (ETV) is a first-line therapy for chronic hepatitis B virus (HBV),
      demonstrating potent suppression of HBV DNA and a high barrier to viral
      resistance. Previous studies revealed that ETV-resistant (ETVr) HBV DNA resulted
      from substitutions in the HBV reverse transcriptase (RT) at positions rtT184,
      rtS202, or rtM250 in combination with lamivudine resistance (LVDr) substitutions
      rtM204I/V+/-rtL180M. In vitro, viral variants exhibit varying degrees of ETV
      susceptibility and replication capacity depending on specific resistance
      substitutions. To explore the potential for additional pathways to ETVr, HBV RT
      sequences from 982 evaluable patients enrolled in 17 ETV clinical studies were
      analyzed. Thirty novel emergent substitutions at amino acid positions not
      previously associated with HBV nucleos(t)ide drug resistance were observed in at
      least 2 patients and were identified in patient-derived HBV with a wild-type,
      LVDr, or ETVr RT sequence. Phenotypic analysis of these substitutions indicated
      that they had no effect on ETV susceptibility. Phenotypic analysis was also
      performed on patient-derived HBV RT sequences from 10 LVD-naive and 13 LVD
      experienced patients with virologic breakthrough and emergent novel substitutions
      while on ETV treatment. One LVD-experienced patient-derived HBV RT harboring LVDr
      substitutions rtL180M+rtM204V with rtA181C displayed reduced ETV susceptibility
      (122-fold greater than wild-type HBV) and remained susceptible to adefovir and
      tenofovir. HBV harboring the rtA181C substitution without LVDr substitutions
      rtL180M+rtM204V remained susceptible to inhibition by ETV, adefovir, and
      tenofovir, although cross-resistance to LVD and telbivudine was observed.
      Conclusion: An integrated genotypic analysis of HBV RT sequences from patients
      with chronic HBV treated with ETV led to the discovery of the novel ETVr
      substitution rtA181C. This substitution was always detected in combination with
      LVDr substitutions rtL180M+rtM204V in ETV-treated patients.

PMID- 30202826
TI  - Preventing Hepatitis B Reactivation During Anti-CD20 Antibody Treatment in the
      Veterans Health Administration.
AB  - Hepatitis B virus (HBV) reactivation may occur with high risk immunosuppression,
      such as anti-cluster of differentiation (CD)20 antibodies (Abs). Appropriate HBV
      prophylaxis during anti-CD20 Ab therapy averts hepatitis, chemotherapy
      disruption, and death. Serologic evidence of prior HBV exposure is present in one
      in nine veterans in the Veterans Health Administration (VHA). In 2014, most (61%
      73%) patients in the VHA who were receiving anti-CD20 Ab treatment underwent HBV
      testing, yet <20% of eligible patients received HBV antiviral prophylaxis. We
      aimed to prevent HBV reactivation by increasing HBV testing and antiviral
      treatment rates among anti-CD20 Ab recipients through prospective interventions.
      A multidisciplinary team of clinicians, pharmacists, and public health
      professionals developed comprehensive prevention systems, including national
      seminars/newsletters/websites; pharmacy criteria for HBV screening/treatment
      prior to anti-CD20 Ab use; changes to national formulary restrictions to expand
      HBV prophylaxis prescribing authority; Medication Use Evaluation Tracker to
      identify omissions; national e-mail alert to all VHA oncology providers detailing
      specific testing and HBV antiviral treatment needs; and a voluntary electronic
      medical record "order check" used at interested facilities (n = 11) to
      automatically assess pretreatment HBV testing and antiviral treatment and only
      generate a reminder to address deficiencies. Analysis of monthly data from June
      2016 through September 2017 among anti-CD20 Ab recipients revealed pre-anti-CD20
      Ab treatment HBV testing increased to 91%-96% and appropriate HBV antiviral
      prophylaxis to 76%-85% nationally following implementation of the intervention.
      Medical centers using the voluntary electronic medical record order check
      increased HBV testing rates to 93%-98% and HBV antiviral prophylaxis rates to
      99%. Conclusion: Multimodal intervention systems to prevent HBV reactivation
      among VHA patients receiving anti-CD20 Ab therapies increased national rates of
      HBV testing to >90% and antiviral prophylaxis to >80%.

PMID- 30202827
TI  - Advanced Hepatocellular Carcinoma Tumor Stage at Diagnosis in the 1945-1965 Birth
      Cohort Reflects Poor Use of Hepatocellular Carcinoma Screening.
AB  - Individuals from the 1945-1965 birth cohort account for the majority of
      hepatocellular carcinoma (HCC) cases in the United States. Understanding trends
      in HCC among this birth cohort is vital given the increasing burden of chronic
      liver disease among this group. We retrospectively evaluated trends and
      disparities in HCC tumor stage at the time of diagnosis among the 1945-1965 birth
      cohort in the United States using the Surveillance, Epidemiology, and End Results
      (SEER) cancer registry. Tumor stage at the time of HCC diagnosis was assessed
      using Milan criteria and SEER HCC staging systems. Among 38,045 patients with HCC
      within the 1945-1965 birth cohort (81.6% male, 50.1% non-Hispanic white, 16.2%
      African American, 12.6% Asian, 19.8% Hispanic), 66.2% had Medicare or commercial
      insurance, 27.2% had Medicaid, and 6.6% were uninsured. During the period 2004
      2006 to 2013-2014, the number of patients with HCC from the 1945-1965 birth
      cohort increased by 58.7% (5.9% increase per year). While the proportion of
      patients with HCC within the Milan criteria increased with time (36.4% in 2003
      2006 to 46.3% in 2013-2014; P < 0.01), less than half were within the Milan
      criteria. On multivariate analysis within the Milan criteria, men were 12% less
      likely to have HCC compared to women, and African Americans were 27% less likely
      to have HCC compared to non-Hispanic whites (odds ratio, 0.73; 95% confidence
      interval, 0.68-0.78; P < 0.01). Conclusion: From 2004 to 2014, the burden of
      newly diagnosed HCC among the 1945-1965 birth cohort increased by 5.9% per year.
      While improvements in earlier staged HCC at diagnosis were observed, the majority
      of patients with HCC among the 1945-1965 birth cohort were beyond the Milan
      criteria at diagnosis; this may reflect poor utilization or suboptimal
      performance of HCC screening tests.

PMID- 30202828
TI  - An Increase in Chromogranin A-Positive, Hormone-Negative Endocrine Cells in
      Pancreas in Cystic Fibrosis.
AB  - We sought to establish whether an increase in chromogranin A-positive, hormone
      negative (CPHN) endocrine cells occurs in the pancreas of patients with cystic
      fibrosis (CF), as potential evidence of neogenesis. Pancreata were obtained at
      autopsy from nondiabetic patients with CF (n = 12) and age-matched nondiabetic
      control subject (CS) individuals without CF (n = 12). In addition, pancreas from
      three diabetic patients with CF was obtained. Pancreas sections were stained for
      chromogranin A, insulin, and a cocktail of glucagon, somatostatin, pancreatic
      polypeptide, and ghrelin and evaluated for the frequency of CPHN cells. There was
      a higher frequency of CPHN cells in islets of the patients with CF compared with
      the CS group. Moreover, CPHN cells occurring as single cells or clusters
      scattered in the exocrine pancreas were also more frequent in patients with CF.
      The increased frequency of CPHN cells in pancreas of patients with CF may
      indicate an attempt at endocrine cell regeneration.

PMID- 30202829
TI  - Diagnosing Nonfunctional Pancreatic NETs in MEN1: The Evidence Base.
AB  - In multiple endocrine neoplasia type 1 (MEN1), nonfunctional pancreatic
      neuroendocrine tumors (NF-pNETs) are the most frequently diagnosed NETs and a
      leading cause of MEN1-related death. The high prevalence and malignant potential
      of NF-pNETs outline the need for an evidence-based screening program, as early
      diagnosis and timely intervention could reduce morbidity and mortality.
      Controversies exist regarding the value of several diagnostic tests. This
      systematic review aims to evaluate current literature and amplify an up-to-date
      evidence-based approach to NF-pNET diagnosis in MEN1. Three databases were
      systematically searched on the diagnostic value of biomarkers and imaging
      modalities. Twenty-seven studies were included and critically appraised (modified
      Quality Assessment of Diagnostic Accuracy Studies). Another 12 studies, providing
      data on age-related penetrance and tumor growth, were included to assess the
      optimal frequency and timing of screening. Based on current literature,
      biomarkers should no longer play a role in the diagnostic process for NF-pNETs,
      as accuracies are too low. Studies evaluating the diagnostic value of imaging
      modalities are heterogeneous with varying risks of bias. For the detection of NF
      pNETs, endoscopic ultrasound (EUS) has the highest sensitivity. A combined
      strategy of EUS and MRI seems to be the most useful. Gallium 68 octreotate-DOTA
      positron emission tomography-CT could be added if NF-pNETs are diagnosed to
      identify metastasis. Reported growth rates were generally low, and two distinct
      phenotypes were observed. Surveillance programs should focus on and be adapted to
      the presence of substantial growth in NF-pNETs. The optimal age to start
      screening must yet be determined, as insufficient evidence for an evidence-based
      recommendation was available.

PMID- 30202830
TI  - High Prevalence of Radiological Vertebral Fractures in Patients With TSH
      Secreting Pituitary Adenoma.
AB  - Background: Bone loss and high risk of fractures have been reported in patients
      with primary hyperthyroidism, whereas data on skeletal health in TSH-secreting
      adenoma (TSH-oma) are scant, and the risk of fractures in this specific clinical
      context has not been investigated so far. In this cross-sectional study, we aimed
      at evaluating for the first time, to our knowledge, the prevalence and
      determinants of radiological vertebral fractures (VFs) in patients with TSH-oma.
      Methods: Twenty-two patients (10 males, 12 females; median age 47 years) with TSH
      oma and 44 patients (20 males, 24 females; median age 49 years) with
      nonfunctioning pituitary adenoma (NFPA) were retrospectively evaluated for
      thoracic VFs using a morphometric approach on lateral chest X-ray routinely
      performed in the presurgical diagnostic workup. Results: The prevalence of VFs
      was significantly higher in TSH-oma vs NFPA (59.1% vs 22.7%; P = 0.003), the
      difference being still significant (odds ratio, 10.5; P = 0.005) after correction
      for the size of pituitary adenomas and biochemical parameters. In TSH-oma, the
      prevalence of VFs was significantly associated with older age (P = 0.007) and
      higher serum free T4 values (P = 0.02). In 20 patients, data on presurgical
      medical therapies of TSH-oma were available. All patients not treated with
      somatostatin receptor ligands were fractured compared with 25% of those who were
      treated with these drugs (P = 0.001). No significant (P = 0.25) association
      between VFs and treatment with methimazole was found. Conclusions: This study
      provides the first evidence, to our knowledge, that patients with TSH-oma may
      develop VFs in close relationship with severity of hyperthyroidism.

PMID- 30202832
TI  - Recurrent Syncope upon Deglutition.

PMID- 30202831
TI  - Secondary Abutment Syndromes of the Wrist in Trauma: A Pictorial Essay.
AB  - Traumatic lesions of the wrist occur frequently and may give rise to
      underdiagnosed secondary abutment syndromes. The latter are a common cause of
      incapacitating pain and limited range of motion, despite minimal or even absent
      alterations on radiographs. Moreover, the complex wrist anatomy often results in
      ignorance or underappreciation of these syndromes. This paper presents a
      pictorial review of frequent and rare secondary abutment syndromes at the wrist
      joint, which - in contrast to primary abutment syndromes - are not based on
      anatomical variants or congenital deformations. The merit of each imaging
      modality is briefly mentioned.

PMID- 30202833
TI  - Esthetic treatment of alveolar ridge atrophy in the anterior maxilla via
      connective tissue graft performed simultaneously with implant placement: A three
      case series.
AB  - OBJECTIVE: The mere osseointegration of an implant should no longer be considered
      a satisfactory criterion for success. Tooth extraction itself and, more
      importantly, possible local comorbidities such as periodontal or endodontic
      diseases, cause a reduction in the gingival volume of the edentulous site due to
      bone atrophy. This reduced volume must be treated and resolved to obtain a
      satisfactory esthetic result, which is an essential factor for successful implant
      rehabilitation. The classic approach to this problem relies on bone augmentation
      procedures. However, the present clinical study is aimed at showing that
      insufficient gingival volume may be corrected simply by resorting to soft tissue
      augmentation, provided that sufficient bone is present to allow implant
      placement. Clinical Considerations: The treatment is described of three cases
      characterized by considerable ridge atrophy that was caused by a simple
      extraction in the first case, periodontal breakdown in the second case, and
      radicular cyst removal in the third case. After healing, all cases presented with
      sufficient bone to allow implant placement, and insufficient volume was treated
      via soft tissue grafts during implant surgery. Esthetic results and patient
      satisfaction were monitored for 2 to 4 years and were very encouraging.
      CONCLUSION: Although the approach described in this report requires further
      investigation, it will likely lead to good results when used to treat a lack of
      pink volume in the most important esthetic area.

PMID- 30202834
TI  - Artificial intelligence, machine learning, neural networks, and deep learning:
      Futuristic concepts for new dental diagnosis.

PMID- 30202835
TI  - Hemostatic gingival retraction agents and their impact on prosthodontic treatment
      steps: A narrative review.
AB  - The purpose of this topic review is to give a general overview of gingival
      retraction agents used during prosthodontic treatment, and the possible
      difficulties connected to them that may be faced by the dentist. Hemostatic
      agents are important for successful gingival retraction and in achieving
      hemostasis. However, these agents may show numerous negative effects on the
      prosthodontic treatment and oral tissues of which the practicing dentist must be
      aware, and which will be elucidated in this review. PubMed and Google Scholar
      databases were searched for publications up to and including 2017. The following
      key words were used in different combinations: "hemostatic agent," "astringent,"
      "astringency," "epinephrine," "ferric sulfate," "aluminum chloride," "hemorrhage
      control," "soft tissue," "hard dental tissue," "self-etch adhesive," "total-etch
      adhesive," "bond strength," "impression," "gypsum," "plaster cast," and "dental
      cast." In the last three decades the hemostatic agents used by practicing
      dentists have changed from epinephrine towards astringents, with AlCl3 and
      Fe2(SO4)3 now the most popular. All of the currently known hemostatic agents
      cause some local, temporary gingival tissue damage, but only epinephrine is known
      to elicit negative systemic effects. Studies concerning the influence of
      hemostatic agents on impression materials show highly contradictory results
      regarding the possible polymerization-inhibiting properties of hemostatic agents,
      probably due to the lack of standardization of methodology. Hemostatic agents
      seem to alter the dentinal surface properties making it more resistant to acid
      etching. Therefore the relatively low acidity of self-etch adhesives when
      compared to total-etch systems may not be strong enough to sufficiently etch a
      more resistant dentinal surface, and consequently may result in lower adhesive
      bond strengths.

PMID- 30202836
TI  - Long-term randomized clinical trial evaluating the effects of fixture surface
      acid-etching and machined collar design on bone healing.
AB  - OBJECTIVES: An implant with an acid-etched fixture surface and internal-hex
      collar may achieve greater osseointegration. The goal of this research was to
      study the effects on long-term bone healing of fixture surface acid-etching and
      machined collar design. METHOD AND MATERIALS: Three two-part implant types were
      compared: standard Branemark (with an external-hex 1.2 mm long machined flat
      collar), Swede-Vent (a copy of the Branemark design, with an identical collar but
      a fixture surface acid-etched to 1 to 3 um), and Screw-Vent (with a fixture
      surface acid-etched identically to that of Swede-Vent, but a longer internal-hex
      machined flat collar that did not require countersinking). Fifty-eight subjects
      each received the three types in alternate fashion at five sites between mental
      foramen, and a fixed full-arch prosthesis. Abutment-implant interface/microgap
      (MG) was placed at the crest, and first bone-to-implant contact point-to microgap
      (fBIC-MG) was measured at mesial and distal sides of each implant. Mean fBIC-MG
      values were compared after 15 to 20 years of function. Statistical analysis was
      based on the mixed linear model with the level of significance set at P < .05 and
      Bonferroni correction for pairwise comparisons. RESULTS: Branemark had less mean
      marginal bone loss (-1.08 mm, standard error [SE] 0.20) compared with Swede-Vent
      (-1.28 mm, SE 0.20), but pairwise comparisons showed that the difference was not
      statistically significant (mean difference of 0.20 mm, P = .662). Screw-Vent had
      the greatest loss (-1.92 mm, SE 0.20), and pairwise comparisons showed that the
      difference was statistically significant compared with Branemark and Swede-Vent
      (difference >= 0.64 mm, P < .001). CONCLUSION: According to accepted standards
      for osseointegration, all three implant types achieved very acceptable long-term
      results. However, while Branemark had the least bone loss, the implant with the
      acid-etched fixture surface and longer internal-hex collar design had the
      greatest loss. Within the confines of this study, shorter collar length of 1.2 mm
      may be more important to limit long-term bone loss with microgap placed at the
      crest.

PMID- 30202837
TI  - An evidence-based evaluation of the concept of centric relation in the 21st
      century.
AB  - The concept and application of a temporomandibular joint (TMJ) relationship
      identified as centric relation (CR) has changed significantly over the past
      century. Originally proposed as a biologically reasonable position where
      maxillary and mandibular dentures should occlude, it later was applied to the
      dentate population as well. The term "ideal" was used by the gnathologic dental
      community as they sought to define the exact details of CR in terms of condyle
      fossa relationships. Assessments of patients' occlusion were then made in
      relation to CR, and discrepancies between the two positions were described as
      being problematic. Since not all dentists have accepted this concept, the
      clinical application of CR has become a topic of major dental confusion and
      controversy. To further complicate things, the formal definitions of CR have
      continuously changed over the past 40 years. In this paper, the biologic
      development of occlusal and TMJ relationships is reviewed, followed by a
      discussion about the validity of applying CR concepts and procedures in
      contemporary clinical and research settings. Special attention is devoted to the
      alleged relationships between occlusion, jaw positions, and temporomandibular
      disorders (TMDs). Current evidence suggests that it is time to stop applying CR
      concepts to the evaluation and dental treatment of healthy dentate individuals.
      For patients with TMDs, it is time to apply current concepts of biopsychosocial
      assessment and management rather than following the 20th century mechanistic
      models of fixing dental and skeletal malalignments.

PMID- 30202838
TI  - Assessment of gingival zenith position and its level relative to age and gender
      in maxillary anterior teeth.
AB  - OBJECTIVE: The gingival tissues surrounding the maxillary anterior teeth play a
      pivotal role in fostering a beautiful smile. The gingival zenith position (GZP)
      and its spatial orientation in the mesiodistal and apicocoronal direction can
      provide a valuable reference point. The present study was undertaken to evaluate
      the GZP and gingival zenith line (GZL) in maxillary anterior teeth in different
      age groups and genders. METHOD AND MATERIALS: The study population comprised 124
      periodontally healthy patients equally divided into 21 to 40 years (Group I) and
      41 to 60 years (Group II) age groups and gender distribution. The parameters of
      vertically bisected midline (VBM), GZP, and GZL were evaluated for all the teeth.
      RESULTS: The GZP was distally placed in 54.68% and 78.12% of the central incisors
      for males and females in Group I, while in Group II it was 65.62% and 75.00%
      respectively. The majority of lateral incisors and canines had coincidence of the
      GZP and VBM. The GZL was found to be at an apical position with reference to the
      GZP of lateral incisors. CONCLUSION: A distal deviation of GZP was observed for
      central incisors, while the GZP coincided with the VBM for lateral incisors and
      canines. The GZL was apically placed in relation to the GZP of lateral incisors.
      These elements can be taken up as reference points in periodontal and restorative
      procedures.

PMID- 30202842
TI  - Identifying the acceptor state in NiO hole collection layers: direct observation
      of exciton dissociation and interfacial hole transfer across a Fe2O3/NiO
      heterojunction.
AB  - NiO is widely utilized as a hole transport layer in solar energy devices where
      light absorption in a photoactive layer is followed by charge separation and hole
      injection into a NiO collection layer. Due to the complex electronic structure of
      the hybridized valence band in NiO, the chemical nature of the hole acceptor
      state has remained an open question, despite the fact that hole localization in
      this material significantly influences device efficiency. To comment on this, we
      present results of ultrafast charge carrier dynamics in a NiO based model
      heterojunction (Fe2O3/NiO) using extreme ultraviolet reflection-absorption (XUV
      RA) spectroscopy. Element specific XUV-RA spectroscopy demonstrates the formation
      of transient Ni3+ within 10 ps following selective photoexcitation of the
      underlying Fe2O3 substrate. This indicates that hole transfer in this system
      occurs to NiO valence band states composed of significant Ni 3d character.
      Additionally, we show that this hole injection process proceeds via a two-step
      sequential mechanism where fast, field-driven exciton dissociation occurs in
      Fe2O3 in 680 +/- 60 fs, followed by subsequent hole injection to NiO in 9.2 +/-
      2.9 ps. These results reveal the chemical nature of the hole acceptor state in
      widely used NiO hole transport layers and provides a direct observation of
      exciton dissociation and interfacial hole transfer in this model system.

PMID- 30202845
TI  - Superconductivity in intercalated buckled two-dimensional materials: KGe2.
AB  - Germanene has emerged as a novel two-dimensional material with various
      interesting properties and applications. Here we report the possibility of
      superconductivity in a stable potassium intercalated germanene compound, KGe2,
      with a transition temperature Tc ~ 11 K, and an electron-phonon coupling of 1.9.
      Applying a 5% tensile strain, which reduces the buckling height by 4.5%, leads to
      the reduction of the electron-phonon coupling by 11% and a slight increase in Tc
      ~ 12 K. That is, strong electron-phonon coupling results from the buckled
      structure of the germanene layers. Despite being an intercalated van der Waals
      material similar to intercalated graphite superconductors, it does not possess an
      occupied interlayer state.

PMID- 30202847
TI  - Estimating divergence times and ancestral breeding systems in Ficus and Moraceae.
AB  - Background and Aims: Although dioecy, which characterizes only 6 % of angiosperm
      species, has been considered an evolutionary dead end, recent studies have
      demonstrated that this is not necessarily the case. Moraceae (40 genera, 1100
      spp., including Ficus, 750 spp.) are particularly diverse in breeding systems
      (including monoecy, gynodioecy, androdioecy and dioecy) and thus represent a
      model clade to study macroevolution of dioecy. Methods: Ancestral breeding
      systems of Ficus and Moraceae were inferred. To do so, a new dated phylogenetic
      tree of Ficus and Moraceae was first reconstructed by combining a revised 12
      fossil calibration set and a densely sampled molecular data set of eight markers
      and 320 species. Breeding system evolution was then reconstructed using both
      parsimony and model-based (maximum likelihood and Bayesian) approaches with this
      new time scale. Key Results: The crown group ages of Ficus and Moraceae were
      estimated in the Eocene (40.6-55.9 Ma) and Late Cretaceous (73.2-84.7 Ma),
      respectively. Strong support was found for ancestral dioecy in Moraceae. Although
      the ancestral state of Ficus remained particularly sensitive to model selection,
      the results show that monoecy and gynodioecy evolved from dioecy in Moraceae, and
      suggest that gynodioecy probably evolved from monoecy in Ficus. Conclusions:
      Dioecy was found not to be an evolutionary dead end in Moraceae. This study
      provides a new time scale for the phylogeny and a new framework of breeding
      system evolution in Ficus and Moraceae.

PMID- 30202846
TI  - Amide-imide tautomerization in the glutamine side chain in enzymatic and
      photochemical reactions in proteins.
AB  - Amide-imide tautomerization presents a pervasive class of chemical
      transformations in organic chemistry of natural compounds. In this Perspective,
      we describe two distinctively different protein systems, in which the amide-imide
      tautomerization in the glutamine side chain takes place in enzymatic or
      photochemical reactions. First, hydrolysis of guanosine triphosphate (GTP)
      catalyzed by the Ras-GAP protein complex suggests the occurrence of the imide
      tautomer of glutamine in reaction intermediates. Second, photoexcitation of
      flavin-binding protein domains (BLUFs) initiates a chain of reactions in the
      chromophore-binding pocket, including amide-imide tautomerization of glutamine.
      Mechanisms of these reactions at the atomic level have been revealed in quantum
      mechanics/molecular mechanics (QM/MM) simulations. To reinforce conclusions on
      the critical role of amide-imide tautomerization of glutamine in these reactions
      we describe results of new quantum chemistry and QM/MM calculations for relevant
      molecular model systems. We reexamine results of the recent IR spectroscopy
      studies of BLUF domains, which provide experimental evidences of Gln
      tautomerization in proteins. We also propose to validate the glutamine-assisted
      mechanism of enzymatic GTP hydrolysis by using IR spectroscopy in a proper range
      of wavenumbers.

PMID- 30202848
TI  - Exosomes/microvesicles microRNA-423-3p derived from cardiac fibroblasts mediates
      the cardioprotective effects of ischemic postconditioning.
AB  - Aims: A recent study reported the cardioprotective effects mediated by cardiac
      fibroblasts (CFs) during acute phase of ischemia-reperfusion injury. Little is
      known about whether exosomes/microvesicles mediate this beneficial effect and
      whether ischemia postconditioning (Postcon) can regulate this process. Here, we
      aimed to investigate the cardioprotective effect of CFs-exosomes/microvesicles
      and whether Psotcon can regulates this effect. Methods and Results: By using a
      transwells co-culture system, we found that hypoxia-reoxygenation (H/R)
      significantly increased the exosomes/microvesicles secretion of CFs and CFs
      protected H9C2 cells against H/R injury and Postcon could amplify these effects.
      Inhibition of CFs exosomes/microvesicles secretion led to a significant
      abrogation on the amplified protective effect of H/R-Postcon. We further
      demonstrated that Postcon enhanced the cardioprotective effect of CFs
      exosomes/microvesicles both in vitro and in vivo. To detect the underlying
      mechanism, exosomes/microvesicles microRNAs were analyzed by RNA sequencing and
      quantitative polymerase chain reaction, our results revealed that miR-423-3p
      expression was selectively enhanced by Postcon in CFs exosomes/microvesicles. By
      co-culture H9C2 cells with CFs-exosomes/microvesicles enriching with miR-423-3p,
      we demonstrated that H/R-Postcon exerted cardioprotective effects by up
      regulation of miR-423-3p in CFs-exosomes/microvesicles. RNA-fluorescence in situ
      hybridization and qPCR demonstrated that the decreasing of miR-423-3p is closely
      related to IRI, by inhibited miR-423-3p expression with its antagomir in vivo, we
      demonstrated that miR-423-3p plays an essential mediate role in I/R-Postcon
      induced cardioprotection against I/R in vivo, Postcon may exert cardioprotective
      effect by up-regulation of miR-423-3p in CFs exosomes/microvesicles. Gain- and
      loss-of-function approaches suggested that rescuing the down-regulated miR-423-3p
      might be a potential strategy to protect the cardiomyocytes against H/R. Using
      computational predictions tools and luciferase reporter assay, we demonstrated
      that miR-423-3p regulates the expression of RAP2C in H9C2 cells, and knockdown of
      RAP2C by siRNA obviously increased cell viability and reduced apoptosis in H9C2
      cells under H/R. Conclusions: In conclusion, we demonstrated, for the first time,
      that CFs participate in cardioprotective effects via an exosomes/microvesicles
      pathway during the acute phase of ischemia-reperfusion injury and Postcon can
      enhance this effect by upregulating the expression of CFs exosomes/microvesicles
      miR-423-3p, which targets the downstream effector RAP2C.

PMID- 30202849
TI  - Guideline-indicated treatments and diagnostics, GRACE risk score, and survival
      for non-ST elevation myocardial infarction.
AB  - Aims: To investigate whether improved survival from non-ST-elevation myocardial
      infarction (NSTEMI), according to GRACE risk score, was associated with guideline
      indicated treatments and diagnostics, and persisted after hospital discharge.
      Methods and results: National cohort study (n = 389 507 patients, n = 232
      hospitals, MINAP registry), 2003-2013. The primary outcome was adjusted all-cause
      survival estimated using flexible parametric survival modelling with time-varying
      covariates. Optimal care was defined as the receipt of all eligible treatments
      and was inversely related to risk status (defined by the GRACE risk score): 25.6%
      in low, 18.6% in intermediate, and 11.5% in high-risk NSTEMI. At 30 days, the use
      of optimal care was associated with improved survival among high [adjusted hazard
      ratio (aHR) -0.66 95% confidence interval (CI) 0.53-0.86, difference in absolute
      mortality rate (AMR) per 100 patients (AMR/100-0.19 95% CI -0.29 to -0.08)], and
      intermediate (aHR = 0.74, 95% CI 0.62-0.92; AMR/100 = -0.15, 95% CI -0.23 to 
      0.08) risk NSTEMI. At the end of follow-up (8.4 years, median 2.3 years), the
      significant association between the use of all eligible guideline-indicated
      treatments and improved survival remained only for high-risk NSTEMI (aHR = 0.66,
      95% CI 0.50-0.96; AMR/100 = -0.03, 95% CI -0.06 to -0.01). For low-risk NSTEMI,
      there was no association between the use of optimal care and improved survival at
      30 days (aHR = 0.92, 95% CI 0.69-1.38) and at 8.4 years (aHR = 0.71, 95% CI 0.39
      3.74). Conclusion: Optimal use of guideline-indicated care for NSTEMI was
      associated with greater survival gains with increasing GRACE risk, but its use
      decreased with increasing GRACE risk.

PMID- 30202851
TI  - High-Dose, Diazoxide-Mediated Insulin Suppression Boosts Weight Loss Induced by
      Lifestyle Intervention.
AB  - Context: Obesity-related hyperinsulinism may impede lifestyle-initiated weight
      loss. Objective: Proof-of-concept study to investigate the amplifying effects of
      diazoxide (DZX)-mediated insulin suppression on lifestyle-induced weight loss in
      nondiabetic, hyperinsulinemic, obese men. Design: Twelve-month study comprising
      an initial 6-month, double-blind trial, followed by a partially de-blinded 6
      month extension in men with obesity with a body mass index of 30 to 37.5 kg/m2
      and a fasting serum C-peptide level >1.00 nM. Patients were randomized into three
      treatment groups: DZX + placebo (DZX + PL), DZX + metformin (DZX + MTF), and
      double PL (PL + PL). Results: At 6 months, DZX treatment was associated with a
      6.1-kg PL-subtracted decline in fat mass (FM), and at 12 months, FM had decreased
      by a total of 15.7 +/- 2.5 kg. Twelve months of DZX treatment was also associated
      with a significant decline in systolic (-6.6%) and diastolic (-8.6%) blood
      pressure and low-density lipoprotein-cholesterol (-18%) and triglycerides (-43%)
      and a 39% rise in high-density lipoprotein-cholesterol. These effects were
      achieved at the cost of a small rise in fasting glucose (95% CI: 0.2 to 1.0 mM)
      and hemoglobin A1c (95% CI: -0.08% to 0.44%). There were no differences between
      DZX monotherapy and the combination of DZX + MTF. Conclusion: High-dose DZX
      treatment of 1 year resulted in a substantial decrease in FM, blood pressure, and
      lipid levels at the cost of a small rise in blood glucose levels.

PMID- 30202852
TI  - Does the composition of polystyrene trays affect Candida spp. biofilm formation?
AB  - The biofilm formation ability of Candida species seems to have a role in the
      prognosis of patients with candidemia. Biofilm formation is usually tested using
      96 well flat bottom polystyrene microtiter plates, although the type of plastic
      used is not commonly reported. This study compares biofilm formation by Candida
      spp. on six types of plates from three brands (three non-tissue-treated and three
      tissue-treated). Thirty isolates of each of the following species were selected:
      C. albicans, C. parapsilosis, C. glabrata, C. tropicalis, as well as 15 isolates
      of C. krusei (n = 135 isolates) from patients with candidemia. Biofilm production
      was evaluated by measuring biomass production and metabolic activity. Our results
      show higher biomass production and metabolic activity of biofilms formed on non
      tissue-treated plates in comparison to those formed on tissue-treated plates (P <
      .001). We only found significant differences in metabolic activity of biofilms
      formed on non-tissue-treated plates (P < .003). All comparisons including biofilm
      formation and metabolic activity among plates of the same brand yielded higher
      biofilm formation on non-treated plates compared to treated plates (P < .001).
      Significant difference in biomass production by C. parapsilosis was only seen
      when comparing between the various tissue-treated plastics (P < .03). In
      contrast, comparisons of different non-tissue-treated tray brands yielded
      significant metabolic activity differences for all species except for C.
      parapsilosis (P < .05). Biofilm formation and metabolic activity is significantly
      affected by the plastic composition of non-tissue-treated trays leading to
      increased biofilm formation.

PMID- 30202853
TI  - The Response of Retailers in Scotland to the Standardised Packaging of Tobacco
      Products Regulations and Tobacco Products Directive.
AB  - Introduction: With most marketing channels prohibited, the retail environment has
      assumed greater importance for tobacco companies, even in markets with a ban on
      the open display of tobacco products. Research has yet to qualitatively explore
      how retailers respond to standardized packaging in a country where this has been
      introduced. Methods: As part of the DISPLAY study, face-to-face interviews were
      conducted with 24 small retailers in Scotland between May 23 and June 26, 2017;
      the interviews were conducted after The Standardised Packaging of Tobacco
      Products Regulations and the Tobacco Products Directive were fully implemented.
      Results: We found high retailer compliance with the legislation. With price
      marked packs and packs containing less than 20 cigarettes and 30 g of rolling
      tobacco banned, retailers stated that this helped simplify ordering and stock
      management. The removal of price-marked packs also allowed them some flexibility
      to set their own prices, but many chose to stick closely to recommended retail
      price in order to remain competitive and avoid complaints from customers. In
      contrast to one of the tobacco industry's arguments against standardized
      packaging, most retailers suggested that transaction times had not increased,
      even though the changes had only recently come into force. Conclusions: This
      study challenges some of the arguments used against standardized packaging and
      provides an insight into the storage and pricing strategies adopted by retailers
      following the removal of price-marked packs. Implications: This study explores
      the response of the retailers to the introduction of standardized tobacco
      packaging and provides an insight into the storage and pricing strategies adopted
      by retailers following the removal of price-marked packs. It explores the
      importance of the retailer in tobacco companies' desire to maintain tobacco sales
      and challenges some of the arguments used against standardized packaging, such as
      an increase in transaction times. Countries seeking to introduce standardized
      packaging should monitor the experiences of retailers, preferably from
      preimplementation through to post implementation, to help understand how
      retailers respond to this policy and to inform compliance.

PMID- 30202850
TI  - Chromosome-level reference genome and alternative splicing atlas of moso bamboo
      (Phyllostachys edulis).
AB  - Background: Bamboo is one of the most important nontimber forestry products
      worldwide. However, a chromosome-level reference genome is lacking, and an
      evolutionary view of alternative splicing (AS) in bamboo remains unclear despite
      emerging omics data and improved technologies. Results: Here, we provide a
      chromosome-level de novo genome assembly of moso bamboo (Phyllostachys edulis)
      using additional abundance sequencing data and a Hi-C scaffolding strategy. The
      significantly improved genome is a scaffold N50 of 79.90 Mb, approximately 243
      times longer than the previous version. A total of 51,074 high-quality protein
      coding loci with intact structures were identified using single-molecule real
      time sequencing and manual verification. Moreover, we provide a comprehensive AS
      profile based on the identification of 266,711 unique AS events in 25,225 AS
      genes by large-scale transcriptomic sequencing of 26 representative bamboo
      tissues using both the Illumina and Pacific Biosciences sequencing platforms.
      Through comparisons with orthologous genes in related plant species, we observed
      that the AS genes are concentrated among more conserved genes that tend to
      accumulate higher transcript levels and share less tissue specificity.
      Furthermore, gene family expansion, abundant AS, and positive selection were
      identified in crucial genes involved in the lignin biosynthetic pathway of moso
      bamboo. Conclusions: These fundamental studies provide useful information for
      future in-depth analyses of comparative genome and AS features. Additionally, our
      results highlight a global perspective of AS during evolution and diversification
      in bamboo.

PMID- 30202854
TI  - Phylolink: Phylogenetically-based profiling, visualisations and metrics for
      biodiversity.
AB  - Summary: Phylolink is a research collaboration toolkit through which biodiversity
      can be explored from a phylogenetic perspective. It is an update of PhyloJiVE
      that has been integrated into the framework of the Atlas of Living Australia,
      including its spatial portal. Phylolink connects phylogenetic tree nodes with
      species occurrence records, environmental data, and species trait information.
      Features new to Phylolink allow users to upload and download spatial datasets,
      store files and link to the ALA spatial portal, improve graphics and provide the
      novel ability to analyze environmental attributes of species and clades
      distributions. Species richness and phylogenetic diversity comparisons can be
      made among geographic areas. The result is a powerful way of combining data to
      generate flexible and customizable visualizations, profiles and metrics for
      biodiversity. Availability and Implementation: Phylolink is available at the
      Atlas of Living Australia, http://phylolink.ala.org.au/. It works on any browser
      and users can select from a range of stored phylogenetic trees and spatial
      datasets, or upload their own. Supplementary information: Supplementary data are
      available at Bioinformatics online.

PMID- 30202855
TI  - A statewide initiative to train behavioral health providers in smoking cessation.
AB  - Individuals with mental health and substance use disorders smoke at rates two to
      four times higher than the general population and account for over half of
      smoking-related deaths. Building capacity of behavioral health providers to
      provide smoking cessation treatment may decrease smoking prevalence in these
      groups. The present study evaluated a statewide rollout of a capacity building
      training program to teach behavioral health providers to deliver a manualized
      smoking cessation group intervention for patients with mental health and
      substance use disorders. Behavioral health treatment providers (N = 333)
      participated in a day-long training. Pretraining and posttraining evaluations
      were conducted on the day of training to assess changes in confidence, attitudes,
      and knowledge regarding smoking cessation and possible barriers to implementing
      the smoking cessation curriculum in treatment programs. These constructs were
      reassessed in follow-up surveys conducted online 2 and 6 months posttraining. A
      subset of providers participated in follow-up telephone calls to discuss
      implementation of smoking cessation programming. Posttraining evaluations
      indicated that trainees' confidence, attitudes, and knowledge of smoking
      interventions improved. Follow-up surveys indicated that these gains decreased
      but were maintained above baseline. Over one-half of survey respondents reported
      taking at least one implementation step. Interviewees reported that agency and
      staff-level barriers such as difficulty coordinating a group, staff turnover, and
      inadequate time with clients precluded more widespread implementation. Training
      for behavioral health providers is effective in improving confidence, attitudes,
      and knowledge regarding smoking cessation interventions. Consistent
      implementation requires ongoing support and agency problem solving to address
      common barriers.

PMID- 30202856
TI  - Diagnostic Accuracy of Endoscopic Trimodal Imaging and Chromoendoscopy for Lesion
      Characterization in Ulcerative Colitis.
AB  - Background: During surveillance colonoscopy of patients with long-standing
      ulcerative colitis [UC], a variety of dysplastic and non-dysplastic lesions are
      detected. The aim of this study was to address the diagnostic accuracy of
      endoscopic characterization of endoscopic trimodal imaging [ETMI] and
      chromoendoscopy [CE]. ETMI includes the combination of autofluorescence imaging
      [AFI], narrow band imaging [NBI] and white light endoscopy [WLE]. Methods: This
      is a pre-specified additional analysis of a multi-centre, randomized controlled
      trial that compared AFI with CE for dysplasia detection in 210 patients with long
      standing UC [FIND-UC trial]. In the AFI arm, endoscopists used the ETMI system to
      record AFI colour, Kudo pit pattern using NBI and WLE for lesion
      characterization. For AFI, purple colour and ambiguous colour combined with pit
      pattern type III-V on NBI was considered dysplastic. Kudo pit pattern was
      described in the CE arm. For pit pattern description using NBI and CE, type III-V
      was considered dysplastic. Histology was the reference standard. Results: In
      total, 52 dysplastic and 255 non-dysplastic lesions were detected. Overall
      sensitivity for real-time prediction of dysplasia was 76.9% (95% confidence
      interval [CI] 46.2-95.0) for ETMI, and 81.6% [95% CI 65.7-92.3] for CE. Overall
      negative predictive value [NPV] for ETMI was 96.9% [95% CI 92.0-98.8] and 94.7%
      [90.2-97.2] for CE. Conclusions: Sensitivity for endoscopic differentiation of
      dysplastic lesions detected during surveillance of patients with long-standing UC
      seems limited using ETMI and CE. Future research is warranted as the high NPV
      indicates that these techniques are valuable for the exclusion of dysplastic
      lesions [NTR4062].

PMID- 30202857
TI  - Lifestyle and cancer-a joint pairwise association of lifestyle habits with
      subsequent cancer diagnosis.
AB  - Background: Unhealthy behaviours increase cancer risk. However, lifestyle habits
      co-occur and their joint association with cancer is not known. Methods: A survey
      among midlife employees included data on lifestyle habits and covariates (N =
      8960, response rate 67%, 80% women). The joint variables of lifestyle habits were
      prospectively linked with register data on cancer diagnosis (mean follow-up time
      12.1 years). Cox proportional hazard model was used to calculate hazard ratios
      (HR), and their 95% confidence intervals. Results: Smoking was associated with
      subsequent cancer risk and the association was strengthened by inactivity (HR
      1.94, 1.46-2.59) and unhealthy diet (HR 1.92, 1.43-2.57). Smoking combined with
      both low (HR 1.70, 1.19-2.41) and moderate (HR 1.68, 1.27-2.23) alcohol
      consumption was also associated with increased cancer risk, as was unhealthy diet
      combined with moderate alcohol consumption (HR 1.55, 1.17-2.06) and inactivity
      (HR 1.44, 1.10-1.88). Inactivity combined with either low (HR 1.44, 1.06-1.96) or
      moderate (HR 1.47, 1.11-1.95) alcohol use was associated with subsequent cancer
      risk. Conclusions: Key unhealthy behaviours have additive effects. Preventive
      measures should be targeted to especially smokers and those having several
      adverse lifestyle habits.

PMID- 30202858
TI  - Towards a toolkit for the assessment and monitoring of musculoskeletal ageing.
AB  - The complexities and heterogeneity of the ageing process have slowed the
      development of consensus on appropriate biomarkers of healthy ageing. The MRC
      Arthritis Research UK Centre for Integrated research into Musculoskeletal Ageing
      (CIMA) is a collaboration between researchers and clinicians at the Universities
      of Liverpool, Sheffield and Newcastle. One of CIMA's objectives is to 'Identify
      and share optimal techniques and approaches to monitor age-related changes in all
      musculoskeletal tissues, and to provide an integrated assessment of
      musculoskeletal function', i.e. to develop a toolkit for assessing
      musculoskeletal ageing. This toolkit is envisaged as an instrument that can be
      used to characterise and quantify musculoskeletal function during 'normal'
      ageing, lend itself to use in large-scale, internationally important cohorts, and
      provide a set of biomarker outcome measures for epidemiological and intervention
      studies designed to enhance healthy musculoskeletal ageing. Such potential
      biomarkers include: biochemical measurements in biofluids or tissue samples, in
      vivo measurements of body composition, imaging of structural and physical
      properties, and functional tests. The CIMA Toolkit Working Group assessed
      candidate biomarkers of musculoskeletal ageing under these four headings,
      detailed their biological bases, strengths and limitations, and made practical
      recommendations for their use. In addition, the CIMA Toolkit Working Group
      identified gaps in the evidence base and suggested priorities for further
      research on biomarkers of musculoskeletal ageing.

PMID- 30202860
TI  - Pointless spatial modeling.
AB  - The analysis of area-level aggregated summary data is common in many disciplines
      including epidemiology and the social sciences. Typically, Markov random field
      spatial models have been employed to acknowledge spatial dependence and allow
      data-driven smoothing. In the context of an irregular set of areas, these models
      always have an ad hoc element with respect to the definition of a neighborhood
      scheme. In this article, we exploit recent theoretical and computational advances
      to carry out modeling at the continuous spatial level, which induces a spatial
      model for the discrete areas. This approach also allows reconstruction of the
      continuous underlying surface, but the interpretation of such surfaces is
      delicate since it depends on the quality, extent and configuration of the
      observed data. We focus on models based on stochastic partial differential
      equations. We also consider the interesting case in which the aggregate data are
      supplemented with point data. We carry out Bayesian inference and, in the
      language of generalized linear mixed models, if the link is linear, an efficient
      implementation of the model is available via integrated nested Laplace
      approximations. For nonlinear links, we present two approaches: a fully Bayesian
      implementation using a Hamiltonian Monte Carlo algorithm and an empirical Bayes
      implementation, that is much faster and is based on Laplace approximations. We
      examine the properties of the approach using simulation, and then apply the model
      to the classic Scottish lip cancer data.

PMID- 30202859
TI  - Large-scale meta-analysis highlights the hypothalamic-pituitary-gonadal axis in
      the genetic regulation of menstrual cycle length.
AB  - The normal menstrual cycle requires a delicate interplay between the
      hypothalamus, pituitary and ovary. Therefore, its length is an important
      indicator of female reproductive health. Menstrual cycle length has been shown to
      be partially controlled by genetic factors, especially in the follicle
      stimulating hormone beta-subunit (FSHB) locus. A genome-wide association study
      meta-analysis of menstrual cycle length in 44 871 women of European ancestry
      confirmed the previously observed association with the FSHB locus and identified
      four additional novel signals in, or near, the GNRH1, PGR, NR5A2 and INS-IGF2
      genes. These findings not only confirm the role of the hypothalamic-pituitary
      gonadal axis in the genetic regulation of menstrual cycle length but also
      highlight potential novel local regulatory mechanisms, such as those mediated by
      IGF2.

PMID- 30202861
TI  - CD48 and alpha7 nAChR Synergistically Regulate FimH-mediated E. coli K1
      Penetration and Neutrophil Transmigration Across Human Brain Microvascular
      Endothelial Cells.
AB  - FimH-mediated bacterial invasion and polymorphonuclear neutrophil (PMN)
      transmigration across human brain microvascular endothelial cells (HBMEC) are
      required for the pathogenesis of Escherichia coli meningitis. However, the
      underlying mechanism remains unclear. This study demonstrated that the TnphoA
      mutant (22A33) and FimH-knockout mutant (DeltaFimH )of Escherichia coli strain
      E44, which resulted in inactivation of FimH, were less invasive and less
      effective in promoting PMN transmigration than their wildtype strain. FimH
      protein induced PMN transmigration, while calmodulin inhibitor significantly
      blocked this effect. Moreover, immunofluorescence and co-immunoprecipitation
      analysis indicated that co-localized CD48 and alpha7 nAChR formed a complex on
      the surface of HBMEC that is associated with increased cofilin dephosphorylation,
      which could be remarkably enhanced by FimH+ E44. Our study concluded that FimH
      induced E. coli K1 invasion and PMN migration across HBMEC may be mediated by the
      CD48-alpha7nAChR complex in lipid rafts of HBMEC via Ca2+ signaling and cofilin
      dephosphorylation.

PMID- 30202862
TI  - Mitral valve modelling and three-dimensional printing for planning and simulation
      of mitral valve repair.
AB  - OBJECTIVES: The aim of this study was to develop a process for modelling and 3
      dimensional (3D) printing of different mitral valve diseases for procedural
      planning and simulation, based on 3D transoesophageal echocardiography (TOE).
      METHODS: 3D TOE was used to reconstruct a fully dynamic 3D view of the diseased
      valve. Reconstructions were cropped at the level of the valve and captured in mid
      systole to assess the coaptation defect. Reconstructions were then exported as a
      surface mesh. To ensure a watertight and noise-reduced model, the mesh was
      processed using computer-modelling programmes, whereupon the valve was printed in
      3D. For simulation purposes, deformable models were created based on negative
      mould fabrication and cast in tissue-mimicking silicone. Model validation was
      performed by intraoperative assessment of the valvular disease and repair
      strategy. RESULTS: The mitral valves of 10 prospective patients with different
      diseases were modelled. In 6 patients, a 3D printed rigid plastic mitral valve
      was created for procedural planning, and in 4 patients, a silicone-cast replica
      was created for procedural simulation. All models were created to scale, implying
      conservation of in vivo dimensions. Models were validated by in vivo comparison.
      Total workaround time ranged from 3 to 4 h and 2 to 3 days for rigid plastic and
      silicone models, respectively. Costs were ?15 to ?40 and ?300, respectively.
      CONCLUSIONS: We demonstrated the feasibility of creating rigid plastic and tissue
      mimicking silicone mitral valve replications. These models could be used in the
      future to enhance surgical anatomical interpretation, to facilitate planning and
      simulation of complex surgeries and for training purposes.

PMID- 30202864
TI  - On the Spinal Cord Injury During Attempted Cervical Interlaminar Epidural
      Injection of Steroids.

PMID- 30202863
TI  - NAD+-dependent synthesis of a 5'-phospho-ADP-ribosylated RNA/DNA cap by RNA 2'
      phosphotransferase Tpt1.
AB  - RNA 2'-phosphotransferase Tpt1 converts an internal RNA 2'-monophosphate to a 2'
      OH via a two-step NAD+-dependent mechanism in which: (i) the 2'-phosphate attacks
      the C1" of NAD+ to expel nicotinamide and form a 2'-phospho-ADP-ribosylated RNA
      intermediate; and (ii) the ADP-ribose O2" attacks the phosphate of the RNA 2'
      phospho-ADPR intermediate to expel the RNA 2'-OH and generate ADP-ribose 1"-2"
      cyclic phosphate. Tpt1 is an essential component of the fungal tRNA splicing
      pathway that generates a unique 2'-PO4, 3'-5' phosphodiester splice junction
      during tRNA ligation. The wide distribution of Tpt1 enzymes in taxa that have no
      fungal-type RNA ligase raises the prospect that Tpt1 might catalyze reactions
      other than RNA 2'-phosphate removal. A survey of Tpt1 enzymes from diverse
      sources reveals that whereas all of the Tpt1 enzymes are capable of NAD+
      dependent conversion of an internal RNA 2'-PO4 to a 2'-OH (the canonical Tpt1
      reaction), a subset of Tpt1 enzymes also catalyzed NAD+-dependent ADP
      ribosylation of an RNA or DNA 5'-monophosphate terminus. Aeropyrum pernix Tpt1
      (ApeTpt1) is particularly adept in this respect. One-step synthesis of a 5'
      phospho-ADP-ribosylated cap structure by ApeTpt1 (with no subsequent 5'
      phosphotransferase step) extends the repertoire of the Tpt1 enzyme family and the
      catalogue of ADP-ribosylation reactions involving nucleic acid acceptors.

PMID- 30202866
TI  - Patient-clinician relationship seems to affect adherence to analgesic use in
      cancer patients: a cross sectional study in a Taiwanese population.

PMID- 30202865
TI  - Genomic Profiling of BDE-47 Effects on Human Placental Cytotrophoblasts.
AB  - Despite gradual legislative efforts to phase out flame retardants (FRs) from the
      marketplace, polybrominated diphenyl ethers (PBDEs) are still widely detected in
      human maternal and fetal tissues, e.g., placenta, due to their continued global
      application in consumer goods and inherent biological persistence. Recent studies
      in rodents and human placental cell lines suggest that PBDEs directly cause
      placental toxicity. During pregnancy, trophoblasts play key roles in uterine
      invasion, vascular remodeling and anchoring of the placenta-fetal unit to the
      mother. Thus, to study the potential consequences of PBDE exposures on human
      placental development, we used an in vitro model: primary villous
      cytotrophoblasts (CTBs). Following exposures, the endpoints that were evaluated
      included cytotoxicity, function (migration, invasion), the transcriptome, and the
      methylome. In a concentration-dependent manner, common PBDE congeners, BDE-47 and
      -99, significantly reduced cell viability and increased death. Upon exposures to
      sub-cytotoxic concentrations (<= 5uM), we observed BDE-47 accumulation in CTBs
      with limited evidence of metabolism. At a functional level, BDE-47 hindered the
      ability of CTBs to migrate and invade. Transcriptomic analyses of BDE-47 effects
      suggested concentration-dependent changes in gene expression, involving stress
      pathways, e.g., inflammation and lipid/cholesterol metabolism as well as
      processes underlying trophoblast fate, e.g., differentiation, migration, and
      vascular morphogenesis. In parallel assessments, BDE-47 induced low-level global
      increases in methylation of CpG islands, including a subset that were proximal to
      genes with roles in cell adhesion/migration. Thus, using a primary human CTB
      model, we showed that PBDEs induced alterations at cellular and molecular levels,
      which could adversely impact placental development.

PMID- 30202867
TI  - Lethal Effects of Silica Gel-Based CimeXa and Kaolin-Based Surround Dusts Against
      Ixodid (Acari: Ixodidae) Eggs, Larvae, and Nymphs.
AB  - As tick resistance to conventional acaricides becomes more common, alternative
      control tactics are gaining attention. Insecticidal dusts CimeXa and Surround,
      based on silica gel and kaolin, respectively, were assessed against Amblyomma
      americanum (L.) (Ixodida: Ixodidae) eggs, larvae, and nymphs in the laboratory.
      Coverage by the dry dusts, particularly CimeXa, was strongly lethal to larvae and
      to a lesser extent to nymphs. Larval mortality was also high when larvae crawled
      across thin layers of CimeXa and, to a lesser extent, Surround dusts. CimeXa was
      more lethal to nymphs that crawled across a thin layer than Surround. Larval
      mortality after crawling on dried aqueous suspensions of the dusts for 30 min and
      for 48 h caused moderate mortality (<80%) regardless of a 10-fold difference in
      concentration; nymphal mortality was negligible. In a field experiment, CimeXa
      dust strongly reduced numbers of Gulf coast tick, Amblyomma maculatum (Koch)
      (Ixodida: Ixodidae), larvae and nymphs by 24 h. Possible application of CimeXa to
      control other species of ixodid ticks is discussed as well as advantages and
      disadvantages of using dusts for tick control under field conditions.

PMID- 30202868
TI  - Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines
      on the Evaluation and Treatment of Patients With Thoracolumbar Spine Trauma:
      Timing of Surgical Intervention.
AB  - QUESTION: Does early surgical intervention improve outcomes for patients with
      thoracic and lumbar fractures? RECOMMENDATIONS: There is insufficient and
      conflicting evidence regarding the effect of timing of surgical intervention on
      neurological outcomes in patients with thoracic and lumbar fractures. Strength of
      Recommendation: Grade Insufficient It is suggested that "early" surgery be
      considered as an option in patients with thoracic and lumbar fractures to reduce
      length of stay and complications. The available literature has defined "early"
      surgery inconsistently, ranging from <8 h to <72 h after injury. Strength of
      Recommendation: Grade B The full version of the guideline can be reviewed at:
      https://www.cns.org/guideline-chapters/congress-neurological-surgeons-systematic
      review-evidence-based-guidelines/chapter_10.

PMID- 30202869
TI  - Genome wide association study for heat stress induced mortality in a white egg
      layer line.
AB  - High environmental temperature is a serious stress affecting economic and
      biological efficiency of poultry production in tropical and subtropical countries
      that is expected to become more prominent with global climate change. Iowa
      experienced 3 acute heat waves of 11, 3, and 4 d of heat index above 38 degrees C
      in the summer of 2012, which led to production losses and increased bird
      mortality. For the current study, the proportion of daughters that died from heat
      stress during this period was calculated for 118 sire families of an elite White
      Leghorn layer line. The number of daughters per sire ranged from 25 to 111 and
      averaged 68. Average mortality due to heat stress was 8.2%, ranging from 0 to
      24.6%. All sires were genotyped using a 600 K Affymetrix chip. After stringent
      quality filtering (clustering quality, parentage, missing genotypes, MAF) 113,344
      SNPs were retained for the analysis. Method BayesB with pi equal to 0.999, for
      the number of markers fitted not to exceed the number of observations, was
      applied. Markers explained 8% of the phenotypic variance. One 1-Mb window on
      chromosome 5 explained 1.2% of genetic variance. When the number of daughters was
      fitted as a weight in the analysis, the proportion of variance explained by
      markers dropped to 1%, but 9 1-Mb windows explained more than 1% of genetic
      variance on chromosomes 1, 3, 5 (the same top window as in the unweighted
      analysis), 9, 17, and 18. Although the support of the genomic regions associated
      with heat stress resistance identified in this study was not very strong, they
      overlapped with previously reported quantitative trait loci regions for immune
      response and physiological traits in chickens and contained genes that have been
      associated with response to heat stress in other studies. Further research is
      needed to validate the results.

PMID- 30202870
TI  - SequencEnG: an Interactive Knowledge Base of Sequencing Techniques.
AB  - Summary: Next-generation sequencing (NGS) techniques are revolutionizing
      biomedical research by providing powerful methods for generating genomic and
      epigenomic profiles. The rapid progress is posing an acute challenge to students
      and researchers to stay acquainted with the numerous available methods. We have
      developed an interactive online educational resource called SequencEnG (acronym
      for Sequencing Techniques Engine for Genomics) to provide a tree-structured
      knowledge base of 66 different sequencing techniques and step-by-step NGS data
      analysis pipelines comparing popular tools. SequencEnG is designed to facilitate
      barrier-free learning of current NGS techniques and provides a user-friendly
      interface for searching through experimental and analysis methods. Availability
      and implementation: SequencEnG is part of the project KnowEnG (Knowledge Engine
      for Genomics) and is freely available at
      http://education.knoweng.org/sequenceng/.

PMID- 30202871
TI  - The Value of Unique Device Identifiers in Plastic Surgery.

PMID- 30202872
TI  - The impact of intensive versus standard anthelminthic treatment on allergy
      related outcomes, helminth infection intensity and helminth-related morbidity in
      Lake Victoria fishing communities, Uganda: results from the LaVIISWA cluster
      randomised trial.
AB  - Background: Allergy-related disease is increasing in low-income countries.
      Parasitic helminths, common in these settings, may be protective. We hypothesised
      that intensive community-wide anthelminthic mass drug administration (MDA) would
      increase allergy-related diseases, while reducing helminth-related morbidity.
      Methods: In an open, cluster-randomised trial (ISRCTN47196031), we randomised 26
      high-schistosomiasis-transmission fishing villages, Lake Victoria, Uganda, in a
      1:1 ratio to receive community-wide intensive (quarterly single-dose praziquantel
      plus albendazole daily for three days) or standard (annual praziquantel plus six
      monthly single-dose albendazole) MDA. Primary outcomes were recent wheeze, skin
      prick test positivity (SPT) and allergen-specific immunoglobulin E (asIgE) after
      three years' intervention. Secondary outcomes included helminths, haemoglobin and
      hepatosplenomegaly. Results: The outcome survey comprised 3350 individuals.
      Intensive MDA had no effect on wheeze, SPT or asIgE (risk ratios (95% confidence
      intervals): 1.11 (0.64,1.93), 1.10 (0.85,1.42) and 0.96 (0.82,1.12),
      respectively). Intensive MDA reduced S. mansoni infection intensity: prevalence
      from Kato-Katz examination of one stool sample was 23% versus 39% (RR 0.70
      (0.55,0.88)), but the more-sensitive urine circulating cathodic antigen test
      remained positive in 85% participants in both trial arms. Hookworm prevalence was
      8% versus 11% (RR 0.55 (0.31,1.00)). There were no differences in anaemia or
      hepatospenomegaly between trial arms. Conclusions: Despite reductions in S.
      mansoni intensity and hookworm prevalence, intensive MDA had no effect on atopy,
      allergy-related disease or helminth-related pathology. This could be due to
      sustained low-intensity infections, thus a causal link between helminths and
      allergy outcomes cannot be discounted. Intensive community-based MDA has limited
      impact in high-schistosomiasis-transmission fishing communities, in the absence
      of other interventions.

PMID- 30202874
TI  - Coronary lesion complexity and the benefit of potent platelet inhibition after
      percutaneous coronary intervention.

PMID- 30202873
TI  - Influenza hemagglutination-inhibition antibody titer as a mediator of vaccine
      induced protection for influenza B.
AB  - Background: The hemagglutination inhibition (HAI) assay is an established
      correlate of protection for the inactivated influenza vaccine, but the proportion
      of vaccine-induced protection that is mediated by the post-vaccination HAI titer
      has not been assessed. Methods: We used data from a randomized placebo-controlled
      trial of a split-virion inactivated influenza vaccine in children 6-17 years of
      age. Sera were collected before and 30 days after receipt of vaccination or
      placebo, and tested by the HAI assay against B/Brisbane/60/2008-like (B/Victoria
      lineage). We fitted Cox proportional hazards models to the time to laboratory
      confirmed influenza B. We used causal mediation analysis to estimate the
      proportion of the total effect of vaccination that was mediated by higher HAI
      titers. Results: We estimated that vaccine efficacy against confirmed B/Victoria
      infection was 68% (95% CI: 33%, 88%), and post-vaccination HAI titers explained
      57% of the effect of vaccination on protection. Conclusions: The majority of the
      effect of inactivated influenza vaccination in children is mediated by the
      increased HAI titer after vaccination, but other components of the immune
      response to vaccination may also play a role in protection and should be further
      explored. Causal mediation analysis provides a framework to quantify the role of
      various mediators of protection.

PMID- 30202875
TI  - Blaming the PFO in patients with cryptogenic ischaemic stroke: Round 2.

PMID- 30202876
TI  - Implementation trial of school staff health promotion: Polish experiences.
AB  - The paper presents the results of the trial implementation of staff health
      promotion in the Health Promoting Schools (HPS) programme in Poland. The design
      and key results of the summative evaluation of the 3-year project and activities
      of schools after completion of the project are described. Over 900 teachers and
      non-teaching employees from 21 schools participated in the project. Its purpose
      was to verify the schools' ability to take action related to the promotion of
      staff health in the HPSs in Poland. The results of the summative evaluation of
      the project were considered positive and promising. The percentage of persons who
      declared that they take greater care of their health, and teachers who described
      their health as very good, increased. Most employees introduced beneficial
      changes in their health behaviours. In all schools, changes in working conditions
      and personnel relations were introduced. Eighty-two per cent of teachers and
      seventy-five per cent of other employees had a positive attitude to the project
      and ninety per cent declared that the activities ought to be continued. Nearly
      all the schools' project leaders considered it a valuable initiative, had
      personal benefits and satisfaction from its implementation. After completing the
      project, 16/20 schools continued activities promoting the health of employees.
      Since the trial implementation of health promotion among school staff was
      considered a success, in 2016 some indicators relating to school staff health
      were included in the self-evaluation of HPS, and work began to prepare
      coordinators of regional and district HPS networks to work with the schools.

PMID- 30202877
TI  - Nature-inspired engineering of an F-type lectin for increased binding strength.
AB  - Individual lectin-carbohydrate interactions are usually of low affinity. However,
      high avidity is frequently attained by the multivalent presentation of glycans on
      biological surfaces coupled with the occurrence of high order lectin oligomers or
      tandem repeats of lectin domains in the polypeptide. F-type lectins are l-fucose
      binding lectins with a typical sequence motif, HX(26)RXDX(4)R/K, whose residues
      participate in l-fucose binding. We previously reported the presence of a few
      eukaryotic F-type lectin domains with partial sequence duplication that results
      in the presence of two l-fucose-binding sequence motifs. We hypothesized that
      such partial sequence duplication would result in greater avidity of lectin
      ligand interactions. Inspired by this example from Nature, we attempted to
      engineer a bacterial F-type lectin domain from Streptosporangium roseum to attain
      avid binding by mimicking partial duplication. The engineered lectin demonstrated
      12-fold greater binding strength than the wild-type lectin to multivalent
      fucosylated glycoconjugates. However, the affinity to the monosaccharide l-fucose
      in solution was similar and partial sequence duplication did not result in an
      additional functional l-fucose binding site. We also cloned, expressed and
      purified a Branchiostoma floridae F-type lectin domain with naturally occurring
      partial sequence duplication and confirmed that the duplicated region with the F
      type lectin sequence motif did not participate in l-fucose binding. We found that
      the greater binding strength of the engineered lectin from S. roseum was instead
      due to increased oligomerization. We believe that this Nature-inspired strategy
      might be useful for engineering lectins to improve binding strength in various
      applications.

PMID- 30202878
TI  - Infection Rates and Risk Factors for Infection Among Health Workers During Ebola
      and Marburg Virus Outbreaks: A Systematic Review.
AB  - Background: Infection in health workers (HWs) has characterized outbreaks of
      Ebola virus disease (EVD) and Marburg virus disease (MVD). We conducted a
      systematic review to investigate infection and mortality rates and common
      exposure risks in HWs in EVD and MVD outbreaks. Methods: We searched the EMBASE
      and PubMed databases to identify articles posted before 27 December 2017, with no
      language restrictions. Data on the number, frequency, and mortality of HW
      infection and exposure risks were extracted. Results: Ninety-four articles
      related to 22 outbreaks were included. HW infections composed 2%-100% of cases in
      EVD and 5%-50% of cases in MVD outbreaks. Among exposed HWs, 0.6%-92% developed
      EVD, and 1%-10% developed MVD. HW infection rates were consistent through
      outbreaks. The most common exposure risk situations were inadequate personal
      protective equipment and exposure to patients with unrecognized EVD/MVD. Similar
      risks were reported in past EVD/MVD outbreaks and in the recent outbreak in West
      Africa. Conclusions: Many outbreaks reported high proportions of infected HWs.
      Similar HW infection rates and exposure risk factors in both past and recent EVD
      and MVD outbreaks emphasize the need to improve the implementation of appropriate
      infection control measures consistently across all healthcare settings.

PMID- 30202879
TI  - The Expression of Aldolase B in Islets Is Negatively Associated With Insulin
      Secretion in Humans.
AB  - Context: Reduced beta-cell mass, impaired islet function, and dedifferentiation
      are considered causal to development of hyperglycemia and type 2 diabetes. In
      human cohort studies, changes of islet cell-specific expression patterns have
      been associated with diabetes but not directly with in vivo insulin secretion.
      Objective: This study investigates alterations of islet gene expression and
      corresponding gene variants in the context of in vivo glycemic traits from the
      same patients. Methods: Fasting blood was collected before surgery, and
      pancreatic tissue was frozen after resection from 18 patients undergoing
      pancreatectomy. Islet tissue was isolated by laser capture microdissection. Islet
      transcriptome was analyzed using microarray and quantitative RT-PCR. Proteins
      were examined by immunohistochemistry and western blotting. The association of
      gene variants with insulin secretion was investigated with oral glucose tolerance
      test (OGTT)-derived insulin secretion measured in a large cohort of subjects at
      increased risk of type 2 diabetes and with hyperglycemic clamp in a subset.
      Results: Differential gene expression between islets from normoglycemic and
      hyperglycemic patients was prominent for the glycolytic enzyme ALDOB and the
      obesity-associated gene FAIM2. The mRNA levels of both genes correlated
      negatively with insulin secretion and positively with HbA1c. Islets of
      hyperglycemic patients displayed increased ALDOB immunoreactivity in insulin
      positive cells, whereas alpha- and delta-cells were negative. Exposure of
      isolated islets to hyperglycemia augmented ALDOB expression. The minor allele of
      the ALDOB variant rs550915 associated with significantly higher levels of C
      peptide and insulin during OGTT and hyperglycemic clamp, respectively.
      Conclusion: Our analyses suggest that increased ALDOB expression in human islets
      is associated with lower insulin secretion.

PMID- 30202880
TI  - A protein-protein interaction underlies the molecular basis for substrate
      recognition by an adenosine-to-inosine RNA-editing enzyme.
AB  - Adenosine deaminases that act on RNA (ADARs) convert adenosine to inosine within
      double-stranded regions of RNA, resulting in increased transcriptomic diversity,
      as well as protection of cellular double-stranded RNA (dsRNA) from silencing and
      improper immune activation. The presence of dsRNA-binding domains (dsRBDs) in all
      ADARs suggests these domains are important for substrate recognition; however,
      the role of dsRBDs in vivo remains largely unknown. Herein, our studies indicate
      the Caenorhabditis elegans ADAR enzyme, ADR-2, has low affinity for dsRNA, but
      interacts with ADR-1, an editing-deficient member of the ADAR family, which has a
      100-fold higher affinity for dsRNA. ADR-1 uses one dsRBD to physically interact
      with ADR-2 and a second dsRBD to bind to dsRNAs, thereby tethering ADR-2 to
      substrates. ADR-2 interacts with >1200 transcripts in vivo, and ADR-1 is required
      for 80% of these interactions. Our results identify a novel mode of substrate
      recognition for ADAR enzymes and indicate that protein-protein interactions can
      guide substrate recognition for RNA editors.

PMID- 30202882
TI  - Carotenoids, vitamin A, and their association with the metabolic syndrome: a
      systematic review and meta-analysis.
AB  - Context: Modifiable factors that reduce the burden of the metabolic syndrome
      (MetS), particularly plant-derived biomarkers, have been a recent focus of rising
      interest. Objective: This systematic review and meta-analysis, which follows
      PRISMA guidelines, evaluates evidence from a period of 20 years that links
      vitamin A and carotenoids with the occurrence of MetS and following the PRISMA
      guidelines. Data Sources: PubMed and Cochrane databases (January 1997 through
      March 2017) were systematically assessed for studies, including case-control,
      cross-sectional, and cohort studies, that evaluated the associations of MetS with
      carotenoids and retinyl esters and retinol (vitamin A). Data Extraction: Key
      measures of associations were harmonized into odds ratios (ORs) and 95%
      confidence intervals (95%CI) of MetS per 1 standard deviation (SD) of exposure
      using forest plots and random effects models that pooled data points from 11
      cross-sectional studies. Begg's funnel and harvest plots were constructed.
      Results: An inverse association between total carotenoids and MetS was found
      [ORpooled, 0.66; 95%CI, 0.56-0.78; 1 SD ~ 0.82 umol/L; n = 5 studies]. This
      association was the strongest for beta-carotene, followed by alpha-carotene and
      beta-crypotoxanthin. No association was detected between retinol and MetS
      (ORpooled, 1.00; 95%CI, 0.88-1.13; 1 SD ~ 2.14 umol/L; n = 6 studies).
      Publication bias was absent, and harvest plots indicated consistency upon
      replication for beta-carotene and total carotenoid exposures. Conclusions: This
      review and meta-analysis suggests that, unlike retinol, total and individual
      carotenoids were inversely related to MetS.

PMID- 30202881
TI  - Landscape of the complete RNA chemical modifications in the human 80S ribosome.
AB  - During ribosome biogenesis, ribosomal RNAs acquire various chemical modifications
      that ensure the fidelity of translation, and dysregulation of the modification
      processes can cause proteome changes as observed in cancer and inherited human
      disorders. Here, we report the complete chemical modifications of all RNAs of the
      human 80S ribosome as determined with quantitative mass spectrometry. We assigned
      228 sites with 14 different post-transcriptional modifications, most of which are
      located in functional regions of the ribosome. All modifications detected are
      typical of eukaryotic ribosomal RNAs, and no human-specific modifications were
      observed, in contrast to a recently reported cryo-electron microscopy analysis.
      While human ribosomal RNAs appeared to have little polymorphism regarding the
      post-transcriptional modifications, we found that pseudouridylation at two
      specific sites in 28S ribosomal RNA are significantly reduced in ribosomes of
      patients with familial dyskeratosis congenita, a genetic disease caused by a
      point mutation in the pseudouridine synthase gene DKC1. The landscape of the
      entire epitranscriptomic ribosomal RNA modifications provides a firm basis for
      understanding ribosome function and dysfunction associated with human disease.

PMID- 30202883
TI  - Biomarkers of Tobacco Exposure Decrease After Smokers Switch to an E-Cigarette or
      Nicotine Gum.
AB  - Introduction: The aerosol composition of electronic cigarettes (ECs) suggests
      that exposure to toxicants during use is greatly reduced compared to exposure
      from combustible cigarettes (CCs). Methods: This randomized, parallel-group,
      clinical study enrolled smokers to switch to Vuse Solo (VS) Digital Vapor
      Cigarettes (Original or Menthol) or Nicorette 4 mg nicotine gum (NG) in a
      controlled setting. Subjects who smoked CCs ad libitum for 2 days during a
      baseline period were then randomized to ad libitum use of either VS or NG for 5
      days. Biomarkers of 23 toxicants were measured in 24-hour urine samples and blood
      collected at baseline and following product switch. Results: A total of 153
      subjects completed the study. Total nicotine equivalents decreased in all groups,
      but higher levels were observed in the VS groups compared to the NG groups, with
      decreases of 38% and 60%-67%, respectively. All other biomarkers were
      significantly decreased in subjects switched to VS, and the magnitude of
      biomarker decreases was similar to subjects switched to NG. Decreases ranged from
      30% to greater than 85% for constituents such as benzene and acrylonitrile.
      Conclusions: These results indicate that exposure to toxicants when using VS is
      significantly reduced compared to CC smoking, and these reductions are similar to
      those observed with use of NG. Although statistically significantly decreased,
      nicotine exposure is maintained closer to CC smoking with VS use compared to NG
      use. This research suggests that use of VS exposes consumers to fewer and lower
      levels of smoke toxicants than CCs while still providing nicotine to the
      consumer. Implications: This is the first study to report changes in nicotine
      delivery and biomarkers of tobacco exposure following a short-term product switch
      from CCs to either an EC or NG in a controlled environment. The study shows that
      nicotine exposure decreased in both groups but was maintained closer to CC
      smoking with the EC groups. Biomarkers of tobacco combustion decreased to similar
      levels in both EC and gum groups.

PMID- 30202884
TI  - Identifying Attributes that Influence In Vitro-to-In Vivo Concordance by
      Comparing In Vitro Tox21 Bioactivity versus In Vivo DrugMatrix Transcriptomic
      Responses across 130 Chemicals.
AB  - Recent efforts aimed at integrating in vitro high-throughput screening (HTS) data
      into chemical toxicity assessments are necessitating increased understanding of
      concordance between chemical-induced responses observed in vitro versus in vivo.
      This investigation set out to (i) measure concordance between in vitro HTS data
      and transcriptomic responses observed in vivo, focusing on the liver, and (ii)
      identify attributes that can influence concordance. Signal response profiles from
      130 substances were compared between in vitro data produced through Tox21 and
      liver transcriptomic data through DrugMatrix, collected from rats exposed to a
      chemical for <=5 days. A global in vitro-to-in vivo comparative analysis based on
      pathway-level responses resulted in an overall average percent agreement of 79%,
      ranging on a per-chemical basis between 41 and 100%. While concordance amongst
      inactive chemicals was high (89%), concordance amongst chemicals showing in vitro
      activity was only 13%, suggesting that follow-up in vivo and/or orthogonal in
      vitro assays would improve interpretations of in vitro activity. Attributes
      identified to influence concordance included experimental design attributes
      (e.g., cell type), target pathways, and physicochemical properties (e.g., logP).
      The attribute that most consistently increased concordance was dose
      applicability, evaluated by filtering for experimental doses administered to rats
      that were within 10-fold of those related to likely bioactivity, derived using
      Tox21 data and high-throughput toxicokinetic modeling. Together, findings suggest
      that in vitro screening approaches to predict in vivo toxicity are viable
      particularly when certain attributes are considered, including whether activity
      versus inactivity is observed, experimental design, chemical properties, and dose
      applicability.

PMID- 30202885
TI  - TOBMI: Trans-omics block missing data imputation using a k-Nearest Neighbor
      weighted approach.
AB  - Motivation: Stitching together trans-omics data is a powerful approach to assess
      the complex mechanisms of cancer occurrence, progression, and treatment. However,
      the integration process suffers from the "block missing" phenomena when part of
      individuals lacks some omics data. Methods: We proposed a k-nearest neighbor
      (kNN) weighted imputation method for trans-omics block missing data (TOBMIkNN) to
      handle gene-absence individuals in RNA-seq datasets using external information
      obtained from DNA methylation probe datasets. Referencing to multi-hot deck, mean
      imputation, as well as missing cases deletion, we assess the relative error,
      absolute error, inter-omics correlation structure change and variable selection.
      Results: The proposed method, TOBMIkNN reliably imputed RNA-seq data by borrowing
      information from DNA methylation data, and showed superiority over the other
      three methods in imputation error and stability of correlation structure. Our
      study indicates that TOBMIkNN can be used as an advisable method for trans-omics
      block-missing data imputation. Availability: TOBMIkNN is freely available at
      https://github.com/XuesiDong/TOBMI. Supplementary Information: Supplementary data
      are available at Bioinformatics online.

PMID- 30202886
TI  - Association between meconium acetaminophen and childhood neurocognitive
      development in GESTE, a Canadian cohort study.
AB  - Acetaminophen is the only over-the-counter pain reliever that is not
      contraindicated during pregnancy, but recent studies have questioned whether
      acetaminophen is safe for the fetus, particularly the developing brain. This
      prospective birth cohort study probed the previously observed association between
      in utero exposure to acetaminophen and neurodevelopment by using concentrations
      of acetaminophen measured in meconium, which more objectively captures exposure
      of the fetus than maternal report. Exposure, measured by liquid chromatography
      coupled with tandem mass spectrometry, was categorized into non-detection, low
      detection, and high detection levels. At age six to eight years, children
      completed a set of subtests from the Wechsler Intelligence Scale for Children,
      4th edition. Additionally this study examined potential effect modification by
      child sex on the association between acetaminophen exposure and neurodevelopment.
      In fully adjusted models, in utero exposure to acetaminophen was not
      statistically significantly associated with decreased scores on any of the
      examined subtests in all children combined (n = 118). The effect of in utero
      acetaminophen exposure on the Coding subtest was marginally significantly
      different among boys and girls, with girls performing significantly better on the
      task with higher levels of acetaminophen compared to girls with undetectable
      levels of exposure [betagirls, low = 2.83 (0.97, 4.70), betagirls, high = 1.95 (
      0.03, 3.93), betaboys, low = 0.02 (-1.78, 1.81), betaboys, high = -0.39 (-2.09,
      1.31), pinteraction = 0.06]. Effect modification by child sex was not observed on
      other subtests. These results do not support prior reports of adverse
      neurodevelopmental effects of in utero exposure to acetaminophen.

PMID- 30202887
TI  - Female Contribution to IDSA Guideline Publications.

PMID- 30202888
TI  - Stroke prevention in patients with atrial flutter: many questions still
      unanswered.

PMID- 30202889
TI  - A research plan to define Canada's first low-risk gambling guidelines.
AB  - From a public health perspective, gambling shares many of the same
      characteristics as alcohol. Notably, excessive gambling is associated with many
      physical and emotional health harms, including depression, suicidal ideation,
      substance use and addiction and greater utilization of health care resources.
      Gambling also demonstrates a similar 'dose-response' relationship as alcohol-the
      more one gambles, the greater the likelihood of harm. Using the same
      collaborative, evidence-informed approach that produced Canada's Low-Risk Alcohol
      Drinking and Lower Risk Cannabis Use Guidelines, a research team is leading the
      development of the first national Low-Risk Gambling Guidelines (LRGGs) that will
      include quantitative thresholds for safe gambling. This paper describes the
      research methodology and the decision-making process for the project. The
      guidelines will be derived through secondary analyses of several large population
      datasets from Canada and other countries, including both cross-sectional and
      longitudinal data on over 50 000 adults. A scientific committee will pool the
      results and put forward recommendations for LRGGs to a nationally representative,
      multi-agency advisory committee for endorsement. To our knowledge, this is the
      first systematic attempt to generate a workable set of LRGGs from population
      data. Once validated, the guidelines inform public health policy and prevention
      initiatives and will be disseminated to addiction professionals, policy makers,
      regulators, communication experts and the gambling industry. The availability of
      the LRGGs will help the general public make well-informed decisions about their
      gambling activities and reduce the harms associated with gambling.

PMID- 30202890
TI  - Gut microbiota in HIV-infected individuals linked to coronary heart disease.
AB  - Background: HIV-infection is an independent risk factor for coronary heart
      disease (CHD) and associated with perturbation of the gut microbiota. Methods: We
      analyzed gut microbiota in 30 HIV-infected individuals with CHD (CHD+) and 30
      without CHD (CHD-) of the HIV-HEART study group. Results: Gut microbiota linked
      to CHD was associated with lower alpha diversity. Despite insignificant
      differences in beta diversity, co-occurrence networks of bacterial genera clearly
      diverged between CHD+ and CHD- individuals. Multidimensional scaling separated
      HIV-infected individuals into two microbiome clusters, either dominated by the
      genus Prevotella or Bacteroides. The relative abundance of 49 other genera was
      significantly different between both clusters. The Prevotella-rich cluster was
      largely composed of men having sex with men (MSM) (97%) while the Bacteroides
      rich cluster comprised both, MSM (45%) and heterosexual individuals (55%). MSM of
      the Bacteroides-rich cluster were characterized by reduced alpha diversity,
      advanced immunological HIV stage, longer antiretroviral therapy (ART) with more
      ART-regimens and longer use of protease inhibitors, compared with Prevotella-rich
      MSM. Conclusion: Community structures of gut microbiota rather than individual
      species might facilitate risk assessment of CHD in HIV-infected individuals.
      Sexual behaviour appears as an important factor affecting gut microbiota beta
      diversity and should be considered in future studies.

PMID- 30202891
TI  - Signaling specificity in the c-di-GMP-dependent network regulating antibiotic
      synthesis in Lysobacter.
AB  - Enzymes controlling intracellular second messengers in bacteria, such as c-di
      GMP, often affect some but not other targets. How such specificity is achieved is
      understood only partially. Here, we present a novel mechanism that enables
      specific c-di-GMP-dependent inhibition of the antifungal antibiotic production.
      Expression of the biosynthesis operon for Heat-Stable Antifungal Factor, HSAF, in
      Lysobacter enzymogenes occurs when the transcription activator Clp binds to two
      upstream sites. At high c-di-GMP levels, Clp binding to the lower-affinity site
      is compromised, which is sufficient to decrease gene expression. We identified a
      weak c-di-GMP phosphodiesterase, LchP, that plays a disproportionately high role
      in HSAF synthesis due to its ability to bind Clp. Further, Clp binding stimulates
      phosphodiesterase activity of LchP. An observation of a signaling complex formed
      by a c-di-GMP phosphodiesterase and a c-di-GMP-binding transcription factor lends
      support to the emerging paradigm that such signaling complexes are common in
      bacteria, and that bacteria and eukaryotes employ similar solutions to the
      specificity problem in second messenger-based signaling systems.

PMID- 30202892
TI  - Design and conduct of early clinical studies of immunotherapy agent combinations:
      Recommendations from the task force on Methodology for the Development of
      Innovative Cancer Therapies.
AB  - The Methodology for the Development of Innovative Cancer Therapies Task Force
      considered aspects of the design and conduct of early studies of combinations of
      immunotherapy agents during their 2018 meeting. The Task Force defined the
      relevant data to justify combination clinical trials, which includes a robust
      hypothesis for the combination, pre-clinical data with evidence of efficacy and
      an understanding of the pharmacodynamics effects of each agent, and ideally
      evidence of single agent activity. Evaluation of pharmacodynamic biomarkers is
      critical in early phase combination trials, and should be incorporated into trial
      objectives and go/no-go decisions. The Task Force also identified the need to
      develop assessment tools and end-points that capture the unique patterns of
      tumour responses to immunotherapy, including pseudoprogression and
      hyperprogression. At least one additional tumour measurement before baseline, and
      an early CT scan (at 4 weeks for example) would help define the incidence of
      hyperprogression, although a common definition is needed. Finally, the Task Force
      highlighted substantial redundancy and inefficiency in the combination
      immunotherapy space, and recommended the adoption of innovative trial designs.

PMID- 30202893
TI  - Use of Tubular Retractor for Resection of Colloid Cysts: Single Surgeon
      Experience and Review of the Literature.
AB  - BACKGROUND: Colloid cysts are challenging lesions to access. Various surgical
      approaches are utilized which all require brain retraction, creating focal
      pressure, local trauma, and potentially surgical morbidity. Recently, tubular
      retractors have been developed that reduce retraction pressure by distributing it
      radially. Such retractors may be beneficial in colloid cyst resection. OBJECTIVE:
      To retrospectively review a single neurosurgeon's case series, as well as the
      literature, to determine the efficacy and safety profile of transtubular colloid
      cyst resections. We also aim to describe our operative technique for this
      approach. METHODS: We conducted a retrospective review of colloid cyst resections
      using either ViewSite Brain Access System (Vycor Medical, Boca Raton, Florida) or
      BrainPath (NICO, Indianapolis, Indiana) tubular retractors performed by a single
      neurosurgeon from 2015 to 2017 (n = 10). A literature review was performed to
      find all published cases of transtubular colloid cyst resections. RESULTS: Gross
      total resection was achieved in all patients. Early neurologic deficit rate was
      10% (n = 1), and permanent neurologic deficit rate was 0%. There were no
      postoperative seizures or venous injuries. Average hospital stay was 2.0 d. There
      was no evidence of recurrence at average follow-up length of 13.6 mo. A
      literature review demonstrated nine studies (n = 77) with an overall complication
      rate of 7.8%. CONCLUSION: Tubular retractors offer an attractive surgical
      corridor for colloid cyst resections, avoiding much of the morbidity of
      interhemispheric approaches, while minimizing damage to normal cortex. There were
      no permanent complications in our series of ten cases, and a literature review
      found a similarly benign safety profile.

PMID- 30202894
TI  - Prognostic modeling of the immune-centric transcriptome reveals interleukin
      signaling candidates contributing to differential patient outcomes.
AB  - Immunotherapy is a promising advancement in the treatment of NSCLC, although much
      of how lung tumors interact with the immune system in the natural course of
      disease remains unknown. We investigated the impact of the expression of immune
      centric genes and pathways in tumors on patient survival to reveal novel
      candidates for immunotherapeutic research. Tumor transcriptomes and detailed
      clinical characteristics were obtained from NSCLC patients who were participants
      of either the INHALE (Discovery, N=280) or TCGA Lung (Replication, N=1026)
      studies. Expression of 2,253 genes derived from 48 major immune pathways were
      assessed for association with patient prognosis using a multivariable Cox model
      and pathway effects were assessed with an in-house implementation of the GSEA
      algorithm. Prognosis-guided gene and pathway analysis of immune-centric
      expression in tumors revealed significant survival enrichments across both
      cohorts. The Interleukin Signaling pathway, containing 430 genes, was found to be
      statistically and significantly enriched with prognostic signal in both the
      INHALE (p=0.008) and TCGA (p=0.039) datasets. Subsequent leading edge analysis
      identified a subset of genes (N=23) shared between both cohorts, driving the
      pathway enrichment. Cumulative expression of this leading edge gene signature was
      a strong predictor of patient survival (Discovery: HR=1.59, p=3.0*10-8;
      Replication: HR=1.29, p=7.4*10-7). These data demonstrate the impact of immune
      centric expression on patient outcomes in NSCLC. Furthermore, prognostic gene
      effects were localized to discrete immune pathways, of which Interleukin
      Signaling had the greatest impact on overall survival and the subset of genes
      driving these effects have promise for future therapeutic intervention.

PMID- 30202896
TI  - A stone embedded in an intracardiac cyst.

PMID- 30202895
TI  - Modulation of tetrachloroethylene-associated kidney effects by nonalcoholic fatty
      liver or steatohepatitis in male C57BL/6J mice.
AB  - Accounting for genetic and other (e.g., underlying disease states) factors that
      may lead to inter-individual variability in susceptibility to xenobiotic-induced
      injury is a challenge in human health assessments. A previous study demonstrated
      that nonalcoholic fatty liver disease (NAFLD), one of the common underlying
      disease states, enhances tetrachloroethylene (PERC)-associated hepatotoxicity in
      mice. Interestingly, NAFLD resulted in a decrease in metabolism of PERC to
      nephrotoxic glutathione conjugates; we therefore hypothesized that NAFLD would
      protect against PERC-associated nephrotoxicity. Male C57BL/6J mice were fed a low
      fat (LFD), high-fat (31% fat, HFD), or high-fat methionine/choline/folate
      deficient (31% fat, MCD) diets. After 8 weeks mice were administered either a
      single dose of PERC (300 mg/kg i.g.) and euthanized at 1-36 hours post dose, or
      five daily doses of PERC (300 mg/kg/d i.g.) and euthanized 4 hrs after last dose.
      Relative to LFD-fed mice, HFD- or MCD-fed mice exhibited decreased PERC
      concentrations and increased trichloroacetate (TCA) in kidneys. S-(1,2,2
      trichlorovinyl)glutathione (TCVG), S-(1,2,2-trichlorovinyl)-L-cysteine (TCVC),
      and N-acetyl-S-(1,2,2,-trichlorovinyl)-L-cysteine (NAcTCVC) were also
      significantly lower in kidney and urine of HFD- or MCD-fed mice compared to LFD
      fed mice. Despite differences in levels of nephrotoxic PERC metabolites in
      kidney, LFD- and MCD-fed mice demonstrated similar degree of nephrotoxicity.
      However, HFD-fed mice were less sensitive to PERC-induced nephrotoxicity. Thus,
      while both MCD- and HFD-induced fatty liver reduced the delivered dose of
      nephrotoxic PERC metabolites to the kidney, only HFD was protective against PERC
      induced nephrotoxicity, possibly due to greater toxicodynamic sensitivity induced
      by methyl and choline deficiency. These results therefore demonstrate that
      preexisting disease conditions can lead to a complex interplay of toxicokinetic
      and toxicodynamic changes that modulate susceptibility to the toxicity of
      xenobiotics.

PMID- 30202897
TI  - Cohort Differences in Cognitive Impairment and Cognitive Decline among Mexican
      Americans Aged 75 and Older.
AB  - Research suggests the prevalence and incidence of cognitive impairment among
      older adults is decreasing. This analysis used data from nine waves (1993-2016)
      of the Hispanic Established Populations for the Epidemiologic Study of the
      Elderly to assess the cognitive status and cognitive decline for two cohorts of
      Mexican-Americans aged >=75 in 1993/94 versus 2004/05. Logistic regression, joint
      longitudinal-survival models, and illness-death models for interval-censored data
      were used to examine cohort differences in the odds of prevalent cognitive
      impairment, trajectories of cognitive decline, and the risk for 10-year incident
      cognitive impairment, respectively. Results indicated that compared to the
      1993/94 Cohort, the 2004/05 Cohort had higher odds for prevalent cognitive
      impairment (odds ratio: 2.51, 95% confidence interval [CI]: 1.92, 3.29),
      particularly among participants with <4 years of education (odds ratio:2.99 95%
      CI: 2.14, 4.18). Conversely, the 2004/05 Cohort exhibited significantly slower
      rates of cognitive decline (beta^: 0.50, 95% CI: 0.39, 0.62) and had a
      significantly lower risk for incident cognitive impairment (hazard ratio: 0.75,
      95% CI: 0.62, 0.91) compared to the 1993/94 Cohort. This analysis provides mixed
      results for cohort trends in the cognitive health of older Mexican-Americans.
      Continued research is needed to identify risk factors that contribute to these
      population-level trends.

PMID- 30202898
TI  - Sequential Monte Carlo for response adaptive randomized trials.
AB  - Response adaptive randomized clinical trials have gained popularity due to their
      flexibility for adjusting design components, including arm allocation
      probabilities, at any point in the trial according to the intermediate results.
      In the Bayesian framework, allocation probabilities to different treatment arms
      are commonly defined as functionals of the posterior distributions of parameters
      of the outcome distribution for each treatment. In a non-conjugate model,
      however, repeated updates of the posterior distribution can be computationally
      intensive. In this article, we propose an adaptation of sequential Monte Carlo
      for efficiently updating the posterior distribution of parameters as new outcomes
      are observed in a general adaptive trial design. An efficient computational tool
      facilitates implementation of more flexible designs with more frequent interim
      looks that can in turn reduce the required sample size and expected number of
      failures in clinical trials. Moreover, more complex statistical models that
      reflect realistic modeling assumptions can be used for analysis of trial results.

PMID- 30202899
TI  - Editorial: Thematic issue on bacterial protein export: from fundamentals to
      applications.

PMID- 30202900
TI  - Novel trimethoprim resistance gene dfrA34 identified in Salmonella Heidelberg in
      the USA.
AB  - Background: Trimethoprim/sulfamethoxazole is a synthetic antibiotic combination
      recommended for the treatment of complicated non-typhoidal Salmonella infections
      in humans. Resistance to trimethoprim/sulfamethoxazole is mediated by the
      acquisition of mobile genes, requiring both a dfr gene (trimethoprim resistance)
      and a sul gene (sulfamethoxazole resistance) for a clinical resistance phenotype
      (MIC >=4/76 mg/L). In 2017, the CDC investigated a multistate outbreak caused by
      a Salmonella enterica serotype Heidelberg strain with
      trimethoprim/sulfamethoxazole resistance, in which sul genes but no known dfr
      genes were detected. Objectives: To characterize and describe the molecular
      mechanism of trimethoprim resistance in a Salmonella Heidelberg outbreak isolate.
      Methods: Illumina sequencing data for one outbreak isolate revealed a 588 bp ORF
      encoding a putative dfr gene. This gene was cloned into Escherichia coli and
      resistance to trimethoprim was measured by broth dilution and Etest. Phylogenetic
      analysis of previously reported dfrA genes was performed using MEGA. Long-read
      sequencing was conducted to determine the context of the novel dfr gene. Results
      and conclusions: The novel dfr gene, named dfrA34, conferred trimethoprim
      resistance (MIC >=32 mg/L) when cloned into E. coli. Based on predicted amino
      acid sequences, dfrA34 shares less than 50% identity with other known dfrA genes.
      The dfrA34 gene is located in a class 1 integron in a multiresistance region of
      an IncC plasmid, adjacent to a sul gene, thus conferring clinical
      trimethoprim/sulfamethoxazole resistance. Additionally, dfrA34 is associated with
      ISCR1, enabling easy transmission between other plasmids and bacterial strains.

PMID- 30202901
TI  - Evolution of gustatory receptor gene family provides insights into adaptation to
      diverse host plants in nymphalid butterflies.

PMID- 30202902
TI  - Role of Host GPR120 in Mediating Dietary Omega-3 Fatty Acid Inhibition of
      Prostate Cancer.
AB  - Background: GPR120, a G protein-coupled receptor for long-chain polyunsaturated
      fatty acids (FAs), mediates the anti-inflammatory effects of omega-3 (omega-3)
      FAs. We investigated whether host or tumor GPR120 plays a role in the anti
      prostate cancer effects of omega-3 FAs. Methods: MycCap prostate cancer
      allografts were grown in immunocompetent wild-type (WT) and GPR120 knockout (KO)
      mice fed omega-3 (fish oil) or omega-6 (corn oil) diets. Immune cell infiltration
      was quantified by flow cytometry, and gene expression of immune cell markers in
      isolated tumor-associated macrophages (TAMs) was quantified by quantitative real
      time polymerase chain reaction. Archived tissue from a fish oil intervention
      trial was used to correlate gene expression of GPR120 with cell cycle progression
      (CCP) genes and Ki67 index (n = 11-15 per group). All statistical tests were two
      sided. Results: In WT mice (n = 7 per group), dietary omega-3 FAs decreased
      MycCap allograft tumor growth (mean [SD] final tumor volume omega-6 = 491 [437]
      mm3 vs omega-3 = 127 [77] mm3, P = .04), whereas in global GPR120KO mice (n = 7
      per group) omega-3 FAs had no anticancer effects. Dietary omega-3 FAs inhibited
      GPR120KO-MycCaP allografts grown in WT mice (n = 8 per group; mean [SD] final
      tumor volume omega-6 = 776 [767] mm3 vs omega-3 = 36 [34] mm3, P = .02). Omega-3
      FA treatment decreased the number of M2-like TAMs in tumor tissue and gene
      expression of M2 markers in isolated TAMs compared with omega-6 controls in WT (n
      = 7 per group) but not in GPR120KO mice (n = 7 per group). In human tissue,
      higher expression of stromal GPR120 correlated with greater reduction in
      expression of CCP genes in men with prostate cancer on a high-omega-3 diet (r = 
      .57, P = .04). Conclusions: Host GPR120 plays a central role in the anti-prostate
      cancer effects of dietary omega-3 FAs. Future studies are required to determine
      if the anticancer effects of omega-3 FAs are mediated through inhibition of M2
      like macrophages and if host GPR120 status predicts anticancer effects of dietary
      omega-3 FAs in men with prostate cancer.

PMID- 30202903
TI  - Letter to the Editor (Effectiveness of Prenatal Vitamin D Deficiency Screening
      and Treatment Program: A Stratified Randomized Field Trial).

PMID- 30202904
TI  - Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines
      on the Evaluation and Treatment of Patients With Thoracolumbar Spine Trauma:
      Classification of Injury.
AB  - QUESTION 1: Are there classification systems for fractures of the thoracolumbar
      spine that have been shown to be internally valid and reliable (ie, do these
      instruments provide consistent information between different care providers)?
      RECOMMENDATION 1: A classification scheme that uses readily available clinical
      data (eg, computed tomography scans with or without magnetic resonance imaging)
      to convey injury morphology, such as Thoracolumbar Injury Classification and
      Severity Scale or the AO Spine Thoracolumbar Spine Injury Classification System,
      should be used to improve characterization of traumatic thoracolumbar injuries
      and communication among treating physicians. Strength of Recommendation: Grade B.
      QUESTION 2: In treating patients with thoracolumbar fractures, does employing a
      formally tested classification system for treatment decision-making affect
      clinical outcomes? RECOMMENDATION 2: There is insufficient evidence to recommend
      a universal classification system or severity score that will readily guide
      treatment of all injury types and thereby affect outcomes. Strength of
      Recommendation: Grade Insufficient The full version of the guideline can be
      reviewed at: https://www.cns.org/guideline-chapters/congress-neurological
      surgeons-systematic-review-evidence-based-guidelines/chapter_2.

PMID- 30202905
TI  - High and Variable Rates of Repeat-Mediated Mitochondrial Genome Rearrangement in
      a Genus of Plants.
AB  - For 30 years, it has been clear that angiosperm mitochondrial genomes evolve
      rapidly in sequence arrangement (i.e., synteny), yet absolute rates of
      rearrangement have not been measured in any plant group, nor is it known how much
      these rates vary. To investigate these issues, we sequenced and reconstructed the
      rearrangement history of seven mitochondrial genomes in Monsonia (Geraniaceae).
      We show that rearrangements (occurring mostly as inversions) not only take place
      at generally high rates in these genomes but also uncover significant variation
      in rearrangement rates. For example, the hyperactive mitochondrial genome of
      Monsonia ciliata has accumulated at least 30 rearrangements over the last million
      years, whereas the branch leading to M. ciliata and its sister species has
      sustained rearrangement at a rate that is at least ten times lower. Furthermore,
      our analysis of published data shows that rates of mitochondrial genome
      rearrangement in seed plants vary by at least 600-fold. We find that sites of
      rearrangement are highly preferentially located in very close proximity to
      repeated sequences in Monsonia. This provides strong support for the hypothesis
      that rearrangement in angiosperm mitochondrial genomes occurs largely through
      repeat-mediated recombination. Because there is little variation in the amount of
      repeat sequence among Monsonia genomes, the variable rates of rearrangement in
      Monsonia probably reflect variable rates of mitochondrial recombination itself.
      Finally, we show that mitochondrial synonymous substitutions occur in a clock
      like manner in Monsonia; rates of mitochondrial substitutions and rearrangements
      are therefore highly uncoupled in this group.

PMID- 30202906
TI  - Risk of type 2 diabetes and cardiovascular disease in an incident cohort of
      people with psoriatic arthritis: a population-based cohort study.
AB  - Objectives: To determine the risk of type 2 diabetes (T2D) and cardiovascular
      diseases in PsA patients compared with the general population and patients with
      psoriasis. Methods: Incident PsA patients aged 18-89 years were identified in the
      UK Clinical Practice Research Datalink between 1998 and 2014 and were matched
      (1:4 ratio) to a general population cohort and psoriasis cohort. The incidence of
      T2D, cerebrovascular disease, ischaemic heart disease and peripheral vascular
      disease (PVD) was calculated for each study cohort. Conditional Poisson
      regression was used to calculate adjusted relative risks. Results: We identified
      6783 incident cases of PsA. The risk of T2D was significantly higher in the PsA
      cohort than in the general population and the psoriasis cohorts [adjusted
      relative risk 1.40 (CI95 1.15, 1.70) and adjusted relative risk 1.53 (CI95 1.19,
      1.97), respectively]. The incidence of ischaemic heart disease, peripheral
      vascular disease and the three cardiovascular outcomes combined in the PsA cohort
      was significantly higher than in the general population. No significant
      differences in risk were observed between the PsA and psoriasis cohorts for any
      cardiovascular outcome. Conclusion: The development of T2D in an incident
      population of PsA is significantly higher than in psoriasis alone or in a general
      population, whereas the increased risk of cardiovascular disease in PsA and
      psoriasis is similar.

PMID- 30202907
TI  - Letter: Increased Body Mass Index Associated With Reduced Risk of Delayed
      Cerebral Ischemia and Subsequent Infarction After Aneurysmal Subarachnoid
      Hemorrhage.

PMID- 30202908
TI  - Contrasting pectin polymers in guard cell walls of Arabidopsis and the hornwort
      Phaeoceros reflect physiological differences.
AB  - Background and Aims: In seed plants, stomata regulate CO2 acquisition and water
      relations via transpiration, while minimizing water loss. Walls of guard cells
      are strong yet flexible because they open and close the pore by changing shape
      over the substomatal cavity. Pectins are necessary for wall flexibility and
      proper stomata functioning. This study investigates the differences in pectin
      composition in guard cells of two taxa that represent key lineages of plants with
      stomata: Arabidopsis, an angiosperm with diurnal stomatal activity, and
      Phaeoceros, a bryophyte that lacks active stomatal movement. Methods: Using
      immunolocalization techniques in transmission electron microscopy, this study
      describes and compares the localization of pectin molecule epitopes essential to
      stomata function in guard cell walls of Arabidopsis and Phaeoceros. Key Results:
      In Arabidopsis, unesterified homogalacturonans very strongly localize throughout
      guard cell walls and are interspersed with arabinan pectins, while methyl
      esterified homogalacturonans are restricted to the exterior of the wall, the
      ledges and the junction with adjacent epidermal cells. In contrast, arabinans are
      absent in Phaeoceros, and both unesterified and methyl-esterified
      homogalacturonans localize throughout guard cell walls. Conclusions: Arabinans
      and unesterified homogalacturonans are required for wall flexibility, which is
      consistent with active regulation of pore opening in Arabidopsis stomata. In
      contrast, the lack of arabinans and high levels of methyl-esterified
      homogalacturonans in guard cell walls of Phaeoceros are congruent with the
      inability of hornwort stomata to open and close with environmental change.
      Comparisons across groups demonstrate that variations in guard cell wall
      composition reflect different physiological activity of stomata in land plants.

PMID- 30202909
TI  - Sleep Disorders in Early Psychosis: Incidence, Severity, and Association With
      Clinical Symptoms.
AB  - Sleep disturbance is known to be associated with psychosis, but sleep disorders
      (eg, insomnia, nightmare disorder, sleep apnea) have rarely been investigated. We
      aimed to provide the first detailed assessment of sleep disorders and their
      correlates in patients with early psychosis. Sixty outpatients aged between 18
      and 30 with nonaffective psychosis were assessed for sleep disorder presence,
      severity, and treatment using a structured diagnostic interview, sleep diaries,
      and actigraphy. Psychotic experiences, mood, and psychological wellbeing were
      also measured. Forty-eight patients (80%) had at least one sleep disorder, with
      insomnia and nightmare disorder being the most common. Comorbidity of sleep
      disorders within this group was high, with an average of 3.3 sleep disorders per
      patient. Over half of the sleep disorders had been discussed with a clinician but
      almost three-quarters had received no treatment. Treatment according to clinical
      guidelines was rare, occurring in only 8% of cases (n = 13). Sleep disorders were
      significantly associated with increased psychotic experiences, depression,
      anxiety, fatigue, and lower quality of life. Sleep disorders are very common in
      patients with psychosis, may have wide-ranging negative effects, and merit
      routine assessment and treatment in psychiatric practice.

PMID- 30202911
TI  - Disproving the obesity paradox-not.

PMID- 30202910
TI  - Post-treatment Mortality Among Patients With Tuberculosis: A Prospective Cohort
      Study of 10 964 Patients in Vietnam.
AB  - Background: Tuberculosis is the leading infectious cause of death. Steep
      reductions in tuberculosis-related mortality are required to realize the World
      Health Organization's "End Tuberculosis Strategy." However, accurate mortality
      estimates are lacking in many countries, particularly following discharge from
      care. This study aimed to establish the mortality rate among patients with
      pulmonary tuberculosis in Vietnam and to quantify the excess mortality in this
      population. Methods: We conducted a prospective cohort study among adult patients
      treated for smear-positive pulmonary tuberculosis in 70 clinics across Vietnam.
      People living in the same households were recruited as controls. Participants
      were re-interviewed and their survival was established at least 2 years after
      their treatment with an 8-month standardized regimen. The presence of relapse was
      established by linking identifying data on patients and controls to clinic
      registries. Verbal autopsies were performed. The cumulative mortality among
      patients was compared to that among a control population, adjusting for age and
      gender. Results: We enrolled 10964 patients and 25707 household controls. Among
      enrolled tuberculosis patients, 9% of patients died within a median follow-up
      period of 2.9 years: 342 (3.1%) during treatment and 637 (5.8%) after discharge.
      The standardized mortality ratio was 4.0 (95% confidence interval 3.7-4.2) among
      patients with tuberculosis, compared to the control population. Tuberculosis was
      the likely cause of death for 44.7% of these deceased patients. Conclusions:
      Patients treated for tuberculosis had a markedly elevated risk of death,
      particularly in the post-treatment period. Interventions to reduce tuberculosis
      mortality must enhance the early detection of drug-resistance, improve treatment
      effectiveness, and address non-communicable diseases.

PMID- 30202913
TI  - Adiposity Genetic Risk Score Modifies the Association Between Blood Lead Level
      and Body Mass Index.
AB  - Context: Previous epidemiological studies had inconsistent results regarding the
      relationship between blood lead level (BLL) and adiposity. Objective: We aimed to
      investigate the associations of BLL with body mass index (BMI) particularly using
      Mendelian randomization analyses and examine the interaction between obesity
      predisposing genes and BLL on the associations. Design and Setting: A total of
      3922 participants were enrolled from 16 sites in East China in 2014 from the
      Survey on Prevalence in East China for Metabolic Diseases and Risk Factors
      (ChiCTR-ECS-14005052, www.chictr.org.cn). We calculated the weighted BMI genetic
      risk score (GRS) based on 29 variants that were identified and validated in East
      Asians. BLL was measured by atomic absorption spectrometry. Main Outcome Measure:
      BMI was calculated, and BMI >=25 kg/m2 was defined as overweight. Results:
      Multivariable logistic regression analysis demonstrated significant associations
      between BMI with each unit increase in lnBLL (beta = 0.24; 95% CI, 0.08 to 0.40;
      P < 0.001) and each 1-point increase in BMI-GRS (beta = 0.08; 95% CI, 0.05 to
      0.11; P < 0.001). The causal regression coefficients of genetically determined
      BMI for lnBLL were -0.003 (95% CI, -0.075 to 0.070), which showed no
      significance. The GRS modified the association of BLL with BMI and overweight
      (BMI >=25 kg/m2; P for interaction = 0.031 and 0.001, respectively). Each unit of
      lnBLL was associated with 63% higher odds of overweight (OR 1.63; 95% CI, 1.30 to
      2.05) in the highest quartile of GRS, but no significant associations were found
      in the lower three quartiles. Conclusions: The associations of BLL with BMI and
      overweight (BMI >=25 kg/m2) were significantly modulated by BMI genetic
      susceptibility.

PMID- 30202912
TI  - A draft genome assembly of the Chinese sillago (Sillago sinica), the first
      reference genome for Sillaginidae fishes.
AB  - Background: Sillaginidae, also known as smelt-whitings, is a family of benthic
      coastal marine fishes in the Indo-West Pacific that have high ecological and
      economic importance. Many Sillaginidae species, including the Chinese sillago
      (Sillago sinica), have been recently described in China, providing valuable
      material to analyze genetic diversification of the family Sillaginidae. Here, we
      constructed a reference genome for the Chinese sillago, with the aim to set up a
      platform for comparative analysis of all species in this family. Findings: Using
      the single-molecule real-time DNA sequencing platform Pacific Biosciences
      (PacBio) Sequel, we generated ~27.3 Gb genomic DNA sequences for the Chinese
      sillago. We reconstructed a genome assembly of 534 Mb using a strategy that takes
      advantage of complementary strengths of two genome assembly programs, Canu and
      FALCON. The genome size was consistent with the estimated genome size based on k
      mer analysis. The assembled genome consisted of 802 contigs with a contig N50
      length of 2.6 Mb. We annotated 22,122 protein-coding genes in the Chinese sillago
      genomes using a de novo method as well as RNA sequencing data and homologies to
      other teleosts. According to the phylogenetic analysis using protein-coding
      genes, the Chinese sillago is closely related to Larimichthys crocea and
      Dicentrarchus labrax and diverged from their ancestor around 69.5-82.6 million
      years ago. Conclusions: Using long reads generated with PacBio sequencing
      technology, we have built a draft genome assembly for the Chinese sillago, which
      is the first reference genome for Sillaginidae species. This genome assembly sets
      a stage for comparative analysis of the diversification and adaptation of fishes
      in Sillaginidae.

PMID- 30202914
TI  - Acetaminophen (Paracetamol) Exposure During Pregnancy and Pubertal Development in
      Boys and Girls From a Nationwide Puberty Cohort.
AB  - This study explored the association between exposure to acetaminophen during
      pregnancy and pubertal development using data from 15,822 boys and girls in the
      longitudinal Puberty Cohort, nested within The Danish National Birth Cohort. Use
      of acetaminophen was reported three times during pregnancy and six months
      postpartum. In total, 54% of mothers indicated use at least once during
      pregnancy. Between 2012 and 2017, sons and daughters provided information on a
      wide range of pubertal milestones, including Tanner stages, axillary hair growth
      and age at menarche or voice break and first ejaculation, every six months from
      11 years of age until full sexual maturation. Data were analyzed by a regression
      model for interval-censored data, providing adjusted mean monthly differences in
      age at attaining the pubertal milestones according to intrauterine cumulative
      (weeks) and trimester specific acetaminophen exposure. Our results suggested a
      tendency towards slightly earlier attainment of almost all studied markers of
      female pubertal development with increasing number of weeks of exposure (i.e.,
      about 1.5-3 months earlier age at pubic hair, axillary hair and acne development
      comparing unexposed with those prenatally exposed for more than 12 weeks). Male
      pubertal development had no strong association with acetaminophen exposure.

PMID- 30202915
TI  - Systematic editing of synthetic RIG-I ligands to produce effective antiviral and
      anti-tumor RNA immunotherapies.

PMID- 30202916
TI  - Smoking reduces plasma bilirubin: Observational and genetic analyses in the
      Copenhagen General Population Study.
AB  - Introduction: Observational studies have found lower concentrations of plasma
      bilirubin in current smokers compared to former and never smokers. However,
      whether there is a causal relationship between smoking and bilirubin is unknown.
      In a Mendelian randomisation analysis, we tested the hypothesis that higher
      tobacco consumption is causally associated with lower concentrations of plasma
      bilirubin. Methods: We genotyped 103 557 individuals aged 20-100 years from the
      Copenhagen General Population Study for the CHRNA3 rs1051730 genotype, known to
      be associated with higher tobacco consumption. Tobacco consumption was defined as
      daily and cumulative tobacco consumption. Results: In observational multivariable
      adjusted analyses, a 10 g/day higher daily tobacco consumption was associated
      with a 0.28 umol/L (95% confidence interval: 0.20-0.35) lower concentration of
      plasma bilirubin in current smokers and a 10 pack-year higher cumulative smoking
      was associated with a 0.19 umol/L (0.17-0.21) lower concentration of plasma
      bilirubin in former and current smokers. Using the CHRNA3 rs1051730 genotype as a
      proxy for daily and cumulative tobacco consumption, the difference in plasma
      bilirubin per T-allele was -0.12 umol/L (-0.23 to -0.002) in current smokers and 
      0.09 umol/L (-0.15 to -0.01) in current and former smokers combined. Furthermore,
      observationally bilirubin concentrations increased with time from smoking
      cessation in former smokers. Conclusion: Higher daily and cumulative tobacco
      consumption were associated with lower concentrations of plasma bilirubin in
      observational and genetic analyses, suggesting that the association is causal.

PMID- 30202917
TI  - Development of a Protein-Ligand Extended Connectivity (PLEC) fingerprint and its
      application for binding affinity predictions.
AB  - Motivation: Fingerprints (FPs) are the most common small molecule representation
      in cheminformatics. There are a wide variety of fingerprints, and the Extended
      Connectivity Fingerprint (ECFP) is one of the best-suited for general
      applications. Despite the overall FP abundance, only a few FPs represent the 3D
      structure of the molecule, and hardly any encode protein-ligand interactions.
      Results: Here, we present a Protein-Ligand Extended Connectivity (PLEC)
      fingerprint that implicitly encodes protein-ligand interactions by pairing the
      ECFP environments from the ligand and the protein. PLEC fingerprints were used to
      construct different machine learning (ML) models tailored for predicting protein
      ligand affinities (pKi/d). Even the simplest linear model built on the PLEC
      fingerprint achieved Rp = 0.817 on the PDBbind v2016 "core set", demonstrating
      its descriptive power. Availability and implementation: The PLEC fingerprint has
      been implemented in the Open Drug Discovery Toolkit
      (https://github.com/oddt/oddt). Supplementary information: Supplementary data are
      available at Bioinformatics online.

PMID- 30202918
TI  - The impact of different sources of heterogeneity on loss of accuracy from genomic
      prediction models.
AB  - Cross-study validation (CSV) of prediction models is an alternative to
      traditional cross-validation (CV) in domains where multiple comparable datasets
      are available. Although many studies have noted potential sources of
      heterogeneity in genomic studies, to our knowledge none have systematically
      investigated their intertwined impacts on prediction accuracy across studies. We
      employ a hybrid parametric/non-parametric bootstrap method to realistically
      simulate publicly available compendia of microarray, RNA-seq, and whole
      metagenome shotgun microbiome studies of health outcomes. Three types of
      heterogeneity between studies are manipulated and studied: (i) imbalances in the
      prevalence of clinical and pathological covariates, (ii) differences in gene
      covariance that could be caused by batch, platform, or tumor purity effects, and
      (iii) differences in the "true" model that associates gene expression and
      clinical factors to outcome. We assess model accuracy, while altering these
      factors. Lower accuracy is seen in CSV than in CV. Surprisingly, heterogeneity in
      known clinical covariates and differences in gene covariance structure have very
      limited contributions in the loss of accuracy when validating in new studies.
      However, forcing identical generative models greatly reduces the within/across
      study difference. These results, observed consistently for multiple disease
      outcomes and omics platforms, suggest that the most easily identifiable sources
      of study heterogeneity are not necessarily the primary ones that undermine the
      ability to accurately replicate the accuracy of omics prediction models in new
      studies. Unidentified heterogeneity, such as could arise from unmeasured
      confounding, may be more important.

PMID- 30202920
TI  - Oral versus Aerosolized Ribavirin for the Treatment of Respiratory Syncytial
      Virus Infections in Hematopoietic Cell Transplantation Recipients.
AB  - Background: The use of oral ribavirin (ORBV) for respiratory syncytial virus
      (RSV) infections is not well studied. With the drastic increase in the cost of
      aerosolized ribavirin (ARBV), we aimed to compare outcomes of hematopoietic cell
      transplantation (HCT) recipients treated with ORBV or ARBV for RSV infections.
      Methods: We reviewed the records of 124 HCT recipients with RSV infections
      treated with ORBV or ARBV from September 2014 through April 2017. An
      immunodeficiency scoring index (ISI) was used to classify patients as low,
      moderate, or high risk for progression to lower respiratory tract infection (LRI)
      or death. Results: Seventy patients (56%) received ARBV and 54 (44%) ORBV. Both
      groups had a 27% rate of progression to LRI (p=1.00). Mortality rates did not
      significantly differ between groups (30-day: aerosolized 10%, oral 9%, p=1.00; 90
      day: aerosolized 23%, oral 11%, p=0.10). Classification and regression tree
      analysis identified ISI >=7 as an independent predictor of 30-day mortality. For
      patients with ISI >=7, 30-day mortality was significantly increased overall, yet
      remained similar between the aerosolized and oral therapy groups (33% for both).
      After propensity score adjustment, Cox proportional hazards models showed similar
      mortality rates between oral and aerosolized therapy groups (30-day: hazard ratio
      1.12, 95% confidence interval 0.345-3.65, p=0.845; 90-day: hazard ratio 0.52, 95%
      confidence interval 0.192-1.411, p=0.199). Conclusions: HCT recipients with RSV
      infections had similar outcomes when treated with ARBV or ORBV. Oral ribavirin
      may be an effective alternative to aerosolized ribavirin for treatment of RSV in
      HCT recipients, with potential significant cost savings.

PMID- 30202921
TI  - Understanding what we mean by the obesity paradox.

PMID- 30202919
TI  - Characterization of Sexual Trait Development in cyp17a1-Deficient Zebrafish.
AB  - Cytochrome P450 (Cyp)17A1 has both 17alpha-hydroxylase and 17,20-lyase
      activities, which are involved in the steroidogenic pathway that produces
      androgens and estrogens. Previously, a phenotype of all-male cyp17a1-deficient
      zebrafish generated by transcription activatorlike effector nuclease has been
      reported. In the current study, the mechanisms relating to Cyp17a1 that are
      involved in the development of sexual traits, especially gonadal differentiation
      and testicular development, were characterized. We found that the cyp17a1
      deficient fish at 3 months postfertilization (mpf) were all fertile males with
      normal testis and spermatogenesis but compromised male-typical mating behaviors
      and secondary sex characters (SSCs), including breeding tubercles, body
      pigmentation, and anal fin coloration. These results demonstrate that
      spermatogenesis and testicular development are not as susceptible to androgen
      deficiency compared with the formation of male-typical SSCs and mating behaviors
      in zebrafish. The differentiation of the juvenile ovary into the mature ovary
      failed during the critical sexual differentiation stage. This all-male phenotype
      of the cyp17a1-deficient fish could be restored with testosterone or estradiol
      treatment. For testicular development in cyp17a1-deficient fish, a gradually
      increasing number of spermatozoa and testis hypertrophy from 3 to 6 mpf were
      observed, accompanied by constitutively upregulated pituitary gonadotropin FSH
      subunit beta (fshbeta). The hypertrophic testis and enhanced spermatogenesis in
      the cyp17a1-deficient fish at 6 mpf could be effectively rescued by fshbeta
      depletion. These results confirm that adequate estrogen is essential for
      maintaining ovarian differentiation, and they provide new insight into the role
      of FSHbeta in male testicular development and spermatogenesis.

PMID- 30202922
TI  - Specific detection of Lysobacter antibioticus strains in agricultural soil using
      PCR and real-time PCR.
AB  - Lysobacter antibioticus is an important biocontrol bacteria against
      phytopathogens in soil, and with the ability to produce nonvolatile antimicrobial
      metabolites has been extensively characterised. It is important to establish
      applicable techniques to detect and monitor L. antibioticus directly and
      accurately in soil samples. We developed and tested 13 primer sets according to
      phenazine gene (phzA, phzB, phzD, phzF, phzS) and the cyclohexanone monooxygenase
      gene (phzNO1); a pair of primer phzNO1 F1/phzNO1 R1 based on the cyclohexanone
      monooxygenase (phzNO1) gene of L. antibioticus strain OH13 was selected and
      optimized polymerase chain reaction (PCR) amplification conditions for rapid and
      accurate detection. After screening eight strains of L. antibioticus, two strains
      of Lysobacter enzymogenes, one strain of Lysobacter capsici, Arthrobacterium,
      Bacillus, Microbacterium, Burkholderia, Pseudomonas and other bacterial strains
      isolated from different agricultural soils, the phzNO1 F1/phzNO1 R1 primers
      amplified a single PCR band of about 229 bp from L. antibioticus. The detection
      sensitivity with primers phzNO1 F1/phzNO1 R1 was 5.14 * 104 fg/25MUL of genomic
      DNA and 2.254 * 1010 to 2.254 * 1011 colony-forming units/mL for the soil
      samples. Quantitative PCR assays were to develope as a specific method to monitor
      the L. antibioticus population in soil as well as guide soil micro-ecological
      management.

PMID- 30202923
TI  - The population-level impacts of excluding norovirus infected food workers: a
      mathematical modeling study.
AB  - Norovirus is the leading cause of acute gastroenteritis and of foodborne disease
      in the United States. The Food and Drug Administration recommends foodworkers
      infected with norovirus be excluded from work while symptomatic and 48 hours
      after their symptoms subside. Compliance with this recommendation is not ideal
      and the population-level impacts of changes in foodworker compliance have yet to
      be quantified. We aimed to assess population impacts of varying degrees of
      compliance with the current recommendation through a compartmental model. We
      modeled the number and proportion of symptomatic norovirus cases averted in the
      U.S. population, by specific age ranges (0-4 year-olds, 5-17 year-olds, 18-64
      year-olds, and 65+ year-olds), under various scenarios of foodworker exclusion
      (i.e., proportion compliant and days of post-symptomatic exclusion) compared to a
      referent scenario, which assumes 66.6% of norovirus symptomatic foodworkers and
      0% of post-symptomatic foodworkers are excluded. Overall, we estimated 6.0
      million norovirus cases have already been avoided annually under the referent
      scenario and 6.7 million (28%) more cases may be avoided through 100% compliance
      with the current recommendations. Substantial population-level benefits were
      predicted from improved compliance in exclusion of norovirus infected foodworkers
      - benefits that may be realized through policies or programs incentivizing self
      exclusion.

PMID- 30202924
TI  - Austerity and the future of the Brazilian Unified Health System (SUS): health in
      perspective.
AB  - This article proposes an analysis of the fiscal austerity measures of the
      Brazilian government and its unfolding in the public health system. It has
      examined the post-impeachment period of the president of Brazil and the changes
      of the social policies conduct in opposition to the principle of equity and
      universality in health with impacts on Brazilian sovereignty. It was a scientific
      essay on the perspective of the Unified Health System (SUS) and the policy
      development based on fiscal austerity that is taking place in the Brazilian
      political scenario, seeking to articulate a diagnosis of the impact of these
      actions on the structure of the country and the health rights. In this way, we
      conclude that the SUS is in imminent danger and that austerity policies in Brazil
      have denied the social gains achieved from previous governments, contributing to
      the discussion on health systems in the context of the neoliberal economic
      pressure and its impacts on lifestyles and access to the health services of the
      Brazilian people.

PMID- 30202925
TI  - Novel mcr-5.3 variant in a CTX-M-8-producing Escherichia coli ST711 isolated from
      an infected horse.

PMID- 30202926
TI  - Applying a community-based participatory research framework to patient and family
      engagement in the development of patient-centered outcomes research and practice.
AB  - There has been increasing recognition of the need to engage patients, families,
      and other patient stakeholders in research. This article seeks to provide
      understanding and examples of how to apply core principles of community-based
      participatory research (CBPR) in developing patient-centered outcomes research
      (PCOR) that can impact clinical and public health practice. Authors review CBPR
      principles and demonstrate how to translate them into effective PCOR strategies.
      Common themes of CBPR principles and PCOR strategies are related to: (a)
      fostering joint ownership in the identification of health priorities, the
      development and evaluation of research strategies and their design, and the
      dissemination of findings; (b) a keen recognition and appreciation for the
      importance of stakeholder-driven priorities, research, and solutions; (c)
      building capacity of both stakeholders and researchers to engage in research
      collaboratively; and (d) recognizing that conducting the research is not the
      endpoint but continues on with a commitment to dissemination, spread, adoption
      and sustainability. The authors highlight the specific strategies in which these
      CBPR principles can be translated for use in engaging patients and families, and
      including other stakeholders such as care providers, community partner
      organizations, health systems, and insurers, in the research process to ensure
      the development of PCOR.

PMID- 30202928
TI  - Omega-3 Fatty Acids and Prostate Cancer: G Protein-Coupled Receptors to the
      Rescue.

PMID- 30202929
TI  - Carry on editing.
AB  - Introduction or background: Genome editing facilitates alterations to DNA, large
      or subtle, in a precise fashion. In its most popular form it uses the
      programmable endonuclease system, CRISPR/Cas9. Edits can be made to any genome,
      including the human genome. This raises the possibility of genome editing in
      human embryos in both a research and reproductive context. Sources of data: All
      reports of genome editing in human embryos are included here, along with key
      papers examining the science and ethics of human genome editing. Areas of
      agreement: As a basic research tool, genome editing promises to accelerate our
      understanding of genome biology. It also shows great promise as a means of
      combatting disease through so-called somatic genome editing. Areas of
      controversy: Genome editing could be used to prevent human disease transmission
      in a reproductive context. Such germ line interventions are opposed by some, for
      a number of reasons. Some of these reasons are discussed and a comparison is made
      with preimplantation genetic diagnosis (PGD). Growing points: It is important
      that scientists, clinicians, bioethicists and other stakeholders engage widely
      with all those with an interest in genome editing. Areas timely for developing
      research: In addition to offering new insights into human biology, basic
      (fundamental) research will deliver expertise allowing ever more precise and
      controllable genome editing methodologies and allied technologies. A range of
      clear and accessible ethical frameworks must be developed and scrutinized as part
      of a wider societal debate about possible applications of genome editing. In the
      UK, human reproductive genome editing can only take place if a change to primary
      legislation occurs. Inclusive discussions and assessments, involving difficult
      scientific and ethical concepts, must form part of any democratic decision.

PMID- 30202927
TI  - Stress management in the workplace for employees with hypertension: a randomized
      controlled trial.
AB  - While behavioral interventions can improve blood pressure (BP) in individuals
      with hypertension, getting such services to people who could benefit remains
      difficult. Workplace programs have potential as dissemination vehicles. The
      objective is to evaluate the effectiveness of a standardized stress management
      program delivered in groups at the workplace for reducing BP compared with
      enhanced usual care. This randomized controlled trial studied 92 urban medical
      center employees with hypertension randomized into two groups. The intervention
      was a 10-week group workshop on cognitive-behavioral coping skills. Enhanced
      usual care included self-help materials for BP reduction and physician referral.
      Intervention group participants' systolic BP (SBP) decreased 7.5 mm Hg over
      controls between baseline and follow-up, from 149.1 (95% CI: 146.0-152.1) to
      140.0 (95% CI: 134.7-145.2), p < .001. The differential change between
      intervention and enhanced usual care groups (Group * Time interaction) was 7.5 mm
      Hg (t = -2.05; p = .04). Diastolic BP reductions were not significantly
      different. Scores on measures of emotional exhaustion and depressive rumination
      showed significant improvements and correlated with reductions in SBP. There was
      no significant change in the usual care group. A standardized worksite group
      intervention produced clinically meaningful reductions in SBP in participants
      with hypertension.

PMID- 30202930
TI  - Filtering and Inference for stochastic oscillators with distributed delays.
AB  - Motivation: The time evolution of molecular species involved in biochemical
      reaction networks often arises from complex stochastic processes involving many
      species and reaction events. Inference for such systems is profoundly challenged
      by the relative sparseness of experimental data, as measurements are often
      limited to a small subset of the participating species measured at discrete time
      points. The need for model reduction can be realistically achieved for
      oscillatory dynamics resulting from negative translational and transcriptional
      feedback loops (TTFLs) by the introduction of probabilistic time-delays. Although
      this approach yields a simplified model, inference is challenging and subject to
      ongoing research. The linear noise approximation (LNA) has recently been proposed
      to address such systems in stochastic form and will be exploited here. Results:
      We develop a novel filtering approach for the LNA in stochastic systems with
      distributed delays, which allows the parameter values and unobserved states of a
      stochastic negative feedback model to be inferred from univariate time-series
      data. The performance of the methods is tested for simulated data. Results are
      obtained for real data when the model is fitted to imaging data on Cry1, a key
      gene involved in the mammalian central circadian clock, observed via a luciferase
      reporter construct in a mouse suprachiasmatic nucleus (SCN). Availability:
      Programs are written in MATLAB and Statistics Toolbox Release 2016b, The
      MathWorks, Inc., Natick, Massachusetts, United States. Sample code and Cry1 data
      are available on GitHub https://github.com/scalderazzo/FLNADD. Supplementary
      information: Supplementary data are available at Bioinformatics online.

PMID- 30202931
TI  - Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines
      on the Evaluation and Treatment of Patients With Thoracolumbar Spine Trauma:
      Hemodynamic Management.
AB  - QUESTION: Does the active maintenance of arterial blood pressure after injury
      affect clinical outcomes in patients with thoracic and lumbar fractures?
      RECOMMENDATIONS: There is insufficient evidence to recommend for or against the
      use of active maintenance of arterial blood pressure after thoracolumbar spinal
      cord injury. Grade of Recommendation: Grade Insufficient However, in light of
      published data from pooled (cervical and thoracolumbar) spinal cord injury
      patient populations, clinicians may choose to maintain mean arterial blood
      pressures >85 mm Hg in an attempt to improve neurological outcomes. Consensus
      Statement by the Workgroup The full version of the guideline can be reviewed at:
      https://www.cns.org/guideline-chapters/congress-neurological-surgeons-systematic
      review-evidence-based-guidelines/chapter_6.

PMID- 30202932
TI  - Type 2 myocardial infarction.

PMID- 30202933
TI  - Primary Syphilis in the Male Urethra - A Case Report.
AB  - A man with nongonococcal urethritis had negative syphilis serology. We documented
      urethral Treponema pallidum infection using broad-range bacterial polymerase
      chain-reaction and sequencing, targeted polymerase-chain-reaction, and
      immunofluorescence microscopy. The patient subsequently seroconverted for
      syphilis; symptoms resolved with penicillin. Early syphilis may present as
      urethritis. Urethral T. pallidum shedding can occur before seroconversion.

PMID- 30202934
TI  - Haemoglobin Titusville: low oxygen saturations but is the patient hypoxaemic?

PMID- 30202935
TI  - SAFE-clustering: Single-cell Aggregated (From Ensemble) Clustering for Single
      cell RNA-seq Data.
AB  - Motivation: Accurately clustering cell types from a mass of heterogeneous cells
      is a crucial first step for the analysis of single-cell RNA-seq (scRNA-Seq) data.
      Although several methods have been recently developed, they utilize different
      characteristics of data and yield varying results in terms of both the number of
      clusters and actual cluster assignments. Results: Here, we present SAFE
      clustering, Single-cell Aggregated (From Ensemble) clustering, a flexible,
      accurate and robust method for clustering scRNA-Seq data. SAFE-clustering takes
      as input, results from multiple clustering methods, to build one consensus
      solution. SAFE-clustering currently embeds four state-of-the-art methods, SC3,
      CIDR, Seurat and t-SNE + k-means; and ensembles solutions from these four methods
      using three hypergraph-based partitioning algorithms. Extensive assessment across
      12 datasets with the number of clusters ranging from 3 to 14, and the number of
      single cells ranging from 49 to 32,695 showcases the advantages of SAFE
      clustering in terms of both cluster number (18.2 - 58.1% reduction in absolute
      deviation to the truth) and cluster assignment (on average 36.0% improvement, and
      up to 18.5% over the best of the four methods, measured by adjusted rand index).
      Moreover, SAFE-clustering is computationally efficient to accommodate large
      datasets, taking <10 minutes to process 28,733 cells. Availability:
      SAFEclustering, including source codes and tutorial, is freely available at
      https://github.com/yycunc/SAFEclustering. Supplementary information:
      Supplementary data are available at Bioinformatics online.

PMID- 30202936
TI  - Microbiology of high-sugar must fermentation by novel yeasts from the chihuahuan
      desert.
AB  - This work reports important results of aromatic profiles produced by native
      yeasts isolated from desert-grown wine grapes from the south of Chihuahua,
      Mexico. These grapes stand very high temperatures during the ripening season,
      developing high sugar concentration and high pH. Yeast species found in grapes
      were identified by polymerase chain reaction and sequence analysis of the 5.8S
      internal transcribed spacer ribosomal RNA region. Aureobasidium namibiae,
      Sporobolomyces johnsonii, Candida apicola, Hanseniaspora uvarum, Candida
      thaimueangensis, Hanseniaspora opuntiae were identified. All of them can grow at
      glucose concentration of 35% (w/v) and 100 ppm of SO2, and produce low volatile
      acidity (0.2-1.0 g acetic acid/L). Volatile organic compounds analysis showed
      that C. thaimueangensis and one strain of C. apicola produce high levels of
      esters, and Hanseniaspora species produces high levels of higher alcohols and
      carbonyl compounds. The results of this study contribute to the knowledge about
      yeast communities associated with desert-grown winegrape yeasts.

PMID- 30202937
TI  - Crystal structure of the modification-dependent SRA-HNH endonuclease TagI.
AB  - TagI belongs to the recently characterized SRA-HNH family of modification
      dependent restriction endonucleases (REases) that also includes ScoA3IV (Sco5333)
      and TbiR51I (Tbis1). Here, we present a crystal structure of dimeric TagI, which
      exhibits a DNA binding site formed jointly by the nuclease domains, and separate
      binding sites for modified DNA bases in the two protomers. The nuclease domains
      have characteristic features of HNH/betabetaalpha-Me REases, and catalyze nicks
      or double strand breaks, with preference for /RY and RYN/RY sites, respectively.
      The SRA domains have the canonical fold. Their pockets for the flipped bases are
      spacious enough to accommodate 5-methylcytosine (5mC) or 5-hydroxymethylcytosine
      (5hmC), but not glucosyl-5-hydroxymethylcytosine (g5hmC). Such preference is in
      agreement with the biochemical determination of the TagI modification dependence
      and the results of phage restriction assays. The ability of TagI to digest
      plasmids methylated by Dcm (C5mCWGG), M.Fnu4HI (G5mCNGC) or M.HpyCH4IV (A5mCGT)
      suggests that the SRA domains of the enzyme are tolerant to different sequence
      contexts of the modified base.

PMID- 30202938
TI  - Role of Probiotics in Managing Gastrointestinal Dysfunction in Children with
      Autism Spectrum Disorder: An Update for Practitioners.
AB  - Children with autism spectrum disorder (ASD) are 4 times as likely to experience
      gastrointestinal symptoms as children without ASD. The gut microbiota has
      increasingly been the subject of investigation as a contributing factor to these
      symptoms in this population because there is evidence to suggest that alterations
      in the intestinal microflora are correlated with gastrointestinal and ASD symptom
      severity. Probiotic therapy has been proposed as a treatment for augmented
      gastrointestinal symptom severity in children with ASD. This narrative review
      systematically searched the literature to provide an update for practitioners on
      the state of the evidence surrounding probiotic therapy in children with ASD as a
      treatment option for reducing gastrointestinal symptoms. A total of 186 articles
      were screened and 5 articles met the inclusion criteria. A collective sample of
      117 children with ASD is represented and outcomes addressed include improvement
      in gastrointestinal symptoms as well as influence of probiotic supplementation on
      the gut microbiota and ASD symptoms and behavior. There is promising evidence to
      suggest that probiotic therapy may improve gastrointestinal dysfunction,
      beneficially alter fecal microbiota, and reduce the severity of ASD symptoms in
      children with ASD. Future research is still warranted in this area because there
      are methodologic flaws in the available literature and optimal species, strains,
      dosages, and duration of treatment have not been identified.

PMID- 30202939
TI  - Integrated Treatment at the First Stage: Increasing Motivation for Alcohol
      Patients with Comorbid Disorders during Inpatient Detoxification.
AB  - Aims: Co-occurring mental disorders can complicate the detoxification treatment
      process and outcome. The aim of this study is to examine whether a brief
      psychoeducational group counseling session during detoxification treatment can
      increase the motivation for and utilization of subsequent treatments. Short
      summary: Interventions increased utilization of post-detoxification treatment and
      reduced alcohol-related readmissions. Higher depression or trauma scores were
      associated with higher rates of utilization of treatment. Methods: Patients
      received either a brief manualised group intervention on the interrelation of
      alcohol use disorder (AUD) and major depression (MD) or AUD and post-traumatic
      stress disorder (PTSD) or a cognitive training session (control group). Of the
      784 patients treated in the study period, 171 participants were quasi-randomly
      allocated to groups. Self-reported motivation was measured before and after
      intervention, transition into AUD treatment and readmissions were collected after
      detoxification treatment. Results: Participating in any of the intervention
      groups increased the utilization of AUD treatment after inpatient detoxification
      (chi2 = 6.15, P = 0.02) and decreased readmissions 6 months after discharge (chi2
      = 7.46, P = 0.01). Depression and trauma scores moderated the effect:
      associations with the utilization of post-detoxification treatment were found in
      participants with higher depression (OR = 5.84, 95% CI = 1.17-29.04) or trauma
      scores (OR = 10.17, 95% CI = 1.54-67.1). Conclusions: An integrated intervention
      approach for dual diagnosis at the beginning of the treatment can increase
      motivation for continued AUD treatment. Especially affected dual diagnosis
      patients can benefit from this treatment.

PMID- 30202940
TI  - Clinicopathological and Molecular Specificities of Inflammatory Bowel Disease
      Related Colorectal Neoplastic Lesions: The Role of Inflammation.
AB  - Compared with the general population, patients with inflammatory bowel disease
      [IBD] have an increased risk of developing colorectal cancer. Molecular
      mechanisms underlying colorectal carcinogenesis in the setting of IBD are not
      well understood. However, modern molecular investigative tools have facilitated
      the identification of features that help distinguish IBD-related carcinoma from
      sporadic carcinoma. Moreover, with advances in endoscopic technology and improved
      understanding of the natural history, the management of colorectal neoplastic
      lesions in IBD patients has evolved. This review discusses the
      clinicopathological and molecular features of colorectal neoplastic lesions
      complicating IBD. Chronic inflammation is believed to promote the development of
      neoplasia, partly by producing reactive oxygen and nitrogen species [ROS and
      NOS], which may interact with genes involved in carcinogenetic pathways.
      Furthermore, alterations in microbiota and in the innate and adaptive immune
      responses might contribute to this process, particularly by initiating,
      regulating, and sustaining chronic inflammation. Earlier detection and better
      characterization of neoplastic colorectal lesions complicating IBD and a better
      knowledge of the molecular mechanisms underlying carcinogenesis in this setting
      should facilitate improvements in the risk stratification of patients with
      longstanding IBD and in the management of dysplastic and malignant colorectal
      lesions that arise in this setting.

PMID- 30202941
TI  - Considerations for Clinical Trials of Staphylococcus aureus Bloodstream Infection
      in Adults.
AB  - Clinical trials for Staphylococcus aureus bloodstream infections (SAB) are
      broadly grouped into two categories: registrational trials intended to support
      regulatory approval of antibiotics for the treatment of SAB, and strategy trials
      intended to inform clinicians on the best treatment options for SAB among
      existing antibiotics. Both types of SAB trials are urgently needed but have been
      limited by cost, complexity, and regulatory uncertainty. This manuscript reviews
      key SAB trial design considerations for investigators, sponsors, and regulators.

PMID- 30202942
TI  - Programmed death-ligand 1 expression in uncommon epidermal growth factor receptor
      mutation-positive non-small cell lung cancer.

PMID- 30202943
TI  - Effects of rearing triplet lambs on ewe productivity, lamb survival and
      performance, and future ewe performance.
AB  - Increasing prolificacy has been proposed to be the most effective way to increase
      the biological efficiency and profitability of sheep production. However, use of
      prolific breeds and genes with major effects on ovulation rate can increase
      prolificacy to levels that may not be desirable or sustainable in extensive
      rangeland production systems. This study thus evaluated effects of triplet births
      on ewe productivity and ewe and lamb performance. An initial study used 666
      purebred Polypay litters to compare ewes with triplet litters that were required
      to raise all the lambs (Treatment A) with those whose triplet litters were
      reduced to 2 lambs (Treatment R). Adult Polypay ewes had an average litter size
      of 2.35 lambs per litter. The frequency of litters of 3 or more lambs was 43.2%;
      56.0% of lambs were born in litters of 3 or more lambs. Ewes that had singles
      weaned fewer lambs and less body weight (BW) of lambs (P < 0.001; 0.94 lambs and
      40.4 kg, respectively) than ewes that had twins or triplets. Ewes with triplet
      litters in Treatment A weaned more lambs (P < 0.01) and more BW of lambs (P <
      0.05) than ewes that had triplets in Treatment R (2.13 lambs and 62.9 kg,
      respectively, vs. 1.79 lambs and 55.0 kg, respectively), and weaned more lambs
      than ewes that had twins (1.77 lambs; P < 0.01). However, neither group of
      triplet-bearing ewes weaned more BW of lambs than ewes that had twins (58.9 kg; P
      >= 0.34). In 2 sets of data involving 442 purebred Polypay litters and 987
      litters from Polypay or Romanov-White Dorper * Rambouillet ewes mated to terminal
      sires, ewes were required to raise all triplet-born lambs. Death losses for
      triplets in these studies (39.6 and 31.6%, respectively) were higher than those
      in Treatment A of the initial study (26.2%), resulting in greater numbers of
      lambs weaned for triplet, compared to twin, litters (1.79 vs. 1.68, respectively;
      P = 0.02) but no greater weight of lambs weaned (54.3 vs. 55.4 kg, respectively;
      P = 0.17). Based on these 3 sets of data, ewes that were required to rear triplet
      lambs weaned 0.20 more lambs per litter than ewes that had twins but also had
      0.75 additional dead lambs per litter, and thus a lamb mortality overhead of 3.75
      additional dead lambs for each additional weaned lamb. We conclude that there is
      an intermediate optimum prolificacy level for extensive rangeland production
      systems. If optimum prolificacy is exceeded, removal and artificial rearing of
      surplus lambs are necessary to avoid increased lamb death losses.

PMID- 30202944
TI  - Factors perceived to influence healthy eating: a systematic review and meta
      ethnographic synthesis of the literature.
AB  - Context: Dietary risks are leading contributors to global morbidity and mortality
      and disproportionately burden individuals of lower socioeconomic positions.
      Objective: The aim of this review is to understand, holistically, what factors
      are perceived to influence healthy eating and to determine whether perceived
      factors differ when comparing the general population with lower socioeconomic
      subgroups. Data Sources: Four academic databases (MEDLINE, CINAHL, PsycINFO,
      Cochrane Library) and 3 gray literature databases were searched systematically,
      along with reference lists. Study Selection: Studies were included if they were
      qualitative and were conducted with community-dwelling adults in high-income
      countries and if they focused specifically on healthy eating. Eligibility was
      determined through author consensus. Data Extraction: Thirty-nine eligible
      studies (of 11 641 records screened) were identified. Study characteristics were
      extracted using a standard template, and quality appraisal was conducted using
      the Critical Appraisal Skills Program tool. Data synthesis was conducted using
      meta-ethnography, with themes categorized according to the socioecological model.
      Results: Factors across the individual, social, lived, and food environments were
      perceived to influence healthy eating. Meta-ethnography revealed that multiple
      environmental and social factors were frequently reported as barriers to healthy
      eating. While factors were largely generalizable, diet affordability and the
      lower availability of stores offering healthy food appeared to be more salient
      barriers for lower socioeconomic groups. Conclusions: Actions to improve
      population diets should mitigate the barriers to healthy eating to create
      environments that support healthy eating across the socioeconomic gradient.
      Systematic Review Registration: PROSPERO registration number CRD42017065243.

PMID- 30202947
TI  - Stem cell therapies in neurology: the good, the bad and the unknown.

PMID- 30202945
TI  - Development and validation of a prognostic model for overall survival in
      chemotherapy-naive men with metastatic castration-resistant prostate cancer.
AB  - Background: Prognostic models are needed that reflect contemporary practice for
      men with metastatic castration-resistant prostate cancer (mCRPC). We sought to
      identify predictive and prognostic variables for overall survival (OS) in
      chemotherapy-naive men with mCRPC treated with enzalutamide. Patients and
      methods: Patients from the PREVAIL trial database (enzalutamide versus placebo)
      were randomly split 2:1 into training (n=1159) and testing (n=550) sets. Using
      the training set, 23 predefined variables were analyzed and a multivariable model
      predicting OS was developed and validated in an independent testing set. Results:
      Patient characteristics and outcomes were well balanced between training and
      testing sets; median OS was 32.7 months in each. The final validated
      multivariable model included 11 independent prognostic variables. Median OS for
      low-, intermediate-, and high-risk groups (testing set) defined by prognostic
      risk tertiles were not yet reached (NYR) (95% CI NYR-NYR), 34.2 months (31.5
      NYR), and 21.1 months (17.5-25.0), respectively. Hazard ratios (95% CI) for OS in
      the low- and intermediate-risk groups versus high-risk group were 0.20 (0.14
      0.29) and 0.40 (0.30-0.53), respectively. Secondary outcomes of response and
      progression differed widely in model-defined risk groups. Enzalutamide improved
      outcomes in all prognostic risk groups. Conclusions: Our validated prognostic
      model incorporates variables routinely collected in chemotherapy-naive men with
      mCRPC treated with enzalutamide, identifying subsets of patients with widely
      differing survival outcomes that provide useful information for external
      validation, patient care, and clinical trial design. Trial registration:
      ClinicalTrials.gov: NCT01212991.

PMID- 30202946
TI  - The Enabling Reduction of Low-Grade Inflammation in Seniors (ENRGISE) Pilot
      Study: Screening Methods and Recruitment Results.
AB  - Background: The Enabling Reduction of Low-grade Inflammation in Seniors (ENRGISE)
      Pilot Study is a multicenter randomized clinical trial examining the feasibility
      of testing whether omega-3 fish oil (omega-3) and the angiotensin receptor
      blocker losartan alone or in combination can reduce inflammation and improve
      walking speed in older adults with mobility impairment. We describe recruitment
      methods and results. Methods: Eligible participants were 70 years and older, had
      elevated interleukin-6 levels (2.5-30 pg/mL) and mobility impairment. Results: Of
      those who responded to recruitment, 83% responded to mailings. A total of 5,424
      telephone screens were completed; of these, 2,011 (37.1%) were eligible for
      further screening. The most common reasons for ineligibility at the telephone
      screens were lack of mobility impairment or use of angiotensin receptor blockers
      or angiotensin-converting enzyme inhibitors. Of the 1,305 initial screening
      visits, 1,087 participants had slow gait speed (<1 m/s). Of these, 701 (64%) had
      elevated interleukin-6 and were eligible for second screening visits. Of the 582
      second screening visits, 335 (57.6%) were eligible to be randomized. A total of
      289 participants (96% of goal) were randomized: 180 in the omega-3 stratum (240%
      of goal); 43 in the losartan (57% of goal), and 66 in the combination (44% of
      goal). The telephone screen and first screening visit to randomization ratio was
      19 to 1 and 4.5 to 1, respectively. The estimated cost of recruitment per
      randomized participant was $1,782. Conclusion: Recruitment for omega-3 exceeded
      goals, but goals for the losartan and combination strata were not met due to the
      high proportion of participants taking angiotensin receptor blockers or
      angiotensin-converting enzyme inhibitors.

PMID- 30202948
TI  - The mTORC1 component RPTOR is required for maintenance of the foundational
      spermatogonial stem cell pool in mice.
AB  - The self-renewal, proliferation, and differentiation of the spermatogonial
      populations must be finely coordinated in the mammalian testis, as dysregulation
      of these processes can lead to subfertility, infertility, or the formation of
      tumors. There are wide gaps in our understanding of how these spermatogonial
      populations are formed and maintained, and our laboratory has focused on
      identifying the molecular and cellular pathways that direct their development.
      Others and we have shown, using a combination of pharmacologic inhibitors and
      genetic models, that activation of mTOR complex 1 (mTORC1) is important for
      spermatogonial differentiation in vivo. Here, we extend those studies to directly
      test the germ cell-autonomous requirement for mTORC1 in spermatogonial
      differentiation. We created germ cell conditional knockout mice for "regulatory
      associated protein of MTOR, complex 1" (Rptor), which encodes an essential
      component of mTORC1. While germ cell KO mice were viable and healthy, they had
      smaller testes than littermate controls, and no sperm were present in their cauda
      epididymides. We found that an initial cohort of Rptor KO spermatogonia
      proliferated, differentiated, and entered meiosis (which they were unable to
      complete). However, no self-renewing spermatogonia were formed, and thus the
      entire germline was lost by adulthood, resulting in Sertoli cell-only testes.
      These results reveal the cell autonomous requirement for RPTOR in the formation
      or maintenance of the foundational self-renewing spermatogonial stem cell (SSC)
      pool in the mouse testis and underscore complex roles for mTORC1 and its
      constituent proteins in male germ cell development.

PMID- 30202949
TI  - Two cases of CLIPPERS with increased number of perivascular CD20-positive B
      lymphocytes.

PMID- 30202950
TI  - Leadless pacing using the transcatheter pacing system (Micra TPS) in the real
      world: initial Swiss experience from the Romandie region.
AB  - Aims: Leadless pacemakers are implanted in Switzerland since June 2015. Large
      worldwide registries have shown high implant success, low complication rates, and
      good electrical parameters up to 12 months' follow-up. However, data are scarce
      outside the investigational setting. The purpose of this study is to assess the
      real-world experience regarding clinical safety and efficacy of Micra TPS
      (transcatheter pacing system) leadless pacemakers. Methods and results:
      Retrospective observational, multi-centre study designed to assess initial safety
      and efficacy of the Micra TPS in the Swiss Romande region. A total of 92 patients
      were included from four different centres with an implantation success rate of
      97.8% (90 of 92). Thresholds were overall low at implantation (median 0.38 V/0.24
      ms, ranging from 0.13 to 2.88 V/0.24 ms) and remained stable over 1-year follow
      up. The perioperative serious adverse event rate was 6.5% in six patients which
      lead to prolonged hospitalization in five patients and death in one patient. In
      addition, three further major events (3.3%) occurred during an average follow-up
      of 1 year, requiring implantation of a standard transvenous pacemaker in two
      patients, and surgical explantation of the Micra TPS in one patient due to
      intractable ventricular tachycardia. Conclusion: Leadless pacemakers are a
      valuable adjunct for treating selected patients requiring single-chamber pacing.
      However, in this initial experience, major complication rates were high (9.8%).
      The implant procedure requires proper training and should be performed in an
      adequate setting.

PMID- 30202951
TI  - Gatekeeping function of primary care physicians under Japan's free-access system:
      a prospective open cohort study involving 14 isolated islands.
AB  - Background: Gatekeeping is important for strong primary care and cost
      containment. Under Japan's free-access system, patients can access any medical
      institution without referral, which makes it difficult to evaluate the
      gatekeeping function of primary care physicians (PCPs). Objectives: To examine
      the gatekeeping function of PCPs in Japan, we compared the frequencies of visits
      to primary care clinics, referrals to advanced care and hospitalizations between
      14 remote islands and a nationwide survey. Methods: This study was a prospective,
      open cohort study involving 14 isolated islands (12 238 inhabitants) in Okinawa,
      Japan. Participants were all patients who visited the clinics on these islands in
      1 year. Main outcome measures were the incidence of on-island clinic visits and
      referrals to off-island advanced care. Results: There were 54 741 visits to the
      islands' clinics with 2045 referrals to off-island medical facilities, including
      549 visits to emergency departments and 705 hospitalizations. The age- and sex
      standardized incidences of healthcare use per 1000 inhabitants per month were:
      360.0 (95% confidence interval: 359.9 to 360.1) visits to primary care clinics,
      11.6 (11.0 to 12.2) referrals to off-island hospital-based outpatient clinics,
      3.3 (2.8 to 5.2) visits to emergency departments and 4.2 (3.1 to 5.2)
      hospitalizations. Comparison with the nationwide survey revealed a lower
      incidence of visits to hospital-based outpatient clinics in this study, while
      more patients had visited PCPs. Conclusions: The lower incidence of visits to
      secondary care facilities in this study might suggest that introduction of a
      gatekeeping system to Japan would reduce the incidence of referral to advanced
      care.

PMID- 30202952
TI  - Illness among US resident student travellers after return to the USA: a
      GeoSentinel analysis, 2007-17.
AB  - Background: The number of US students studying abroad more than tripled during
      the past 20 years. As study abroad programmes' destinations diversify, students
      increasingly travel to resource-limited countries, placing them at risk for
      infectious diseases. Data describing infections acquired by US students while
      travelling internationally are limited. We describe illnesses among students who
      returned from international travel and suggest how to prevent illness among these
      travellers. Methods: GeoSentinel is a global surveillance network of travel and
      tropical medicine providers that monitors travel-related morbidity. This study
      included the records of US resident student international travellers, 17-24 years
      old, who returned to the USA, had a confirmed travel-related illness at one of 15
      US GeoSentinel sites during 2007-17 and had a documented exposure region. Records
      were analysed to describe demographic and travel characteristics and diagnoses.
      Results: The study included 432 students. The median age was 21 years; 69% were
      female. More than 70% had a pre-travel consultation with a healthcare provider.
      The most common exposure region was sub-Saharan Africa (112; 26%). Students were
      most commonly exposed in India (44; 11%), Ecuador (28; 7%), Ghana (25; 6%) and
      China (24; 6%). The median duration of travel abroad was 40 days (range: 1-469)
      and presented to a GeoSentinel site a median of 8 days (range: 0-181) after
      travel; 98% were outpatients. Of 581 confirmed diagnoses, the most common
      diagnosis category was gastrointestinal (45%). Acute diarrhoea was the most
      common gastrointestinal diagnosis (113 of 261; 43%). Thirty-one (7%) students had
      vector-borne diseases [14 (41%) malaria and 11 (32%) dengue]. Three had vaccine
      preventable diseases (two typhoid; one hepatitis A); two had acute human
      immunodeficiency virus infection. Conclusions: Students experienced travel
      related infections, despite the majority having a pre-travel consultation. US
      students should receive pre-travel advice, vaccinations and chemoprophylaxis to
      prevent gastrointestinal, vector-borne, sexually transmitted and vaccine
      preventable infections.

PMID- 30202953
TI  - Lymph-node ratio predicts survival among the different stages of non-small-cell
      lung cancer: a multicentre analysis.
AB  - OBJECTIVES: The prognostic role of the number of resected and metastatic lymph
      nodes in non-small-cell lung cancer (NSCLC) is still being debated. The aim of
      this study was to evaluate the impact of lymphadenectomy in addition to the
      already validated variables in NSCLC survival. METHODS: From January 2002 to
      December 2012, data on 4858 patients with NSCLC undergoing anatomical lung
      resection and hilomediastinal lymphadenectomy in 6 institutions were analysed
      retrospectively. Established prognostic factors in addition to the number of
      resected lymph nodes and the ratio between the number of metastatic lymph nodes
      and the number of resected lymph nodes (NR) were correlated to overall survival
      (OS) and disease-free survival (DFS) using the multivariable Cox regression
      model. Harrell's C-statistic with the 95% confidence interval (CI) was
      determined. Analysis by means of maximally selected log-rank statistics was
      performed to find optimal cut-off points in order to split patients into groups
      with different outcome probabilities. RESULTS: The median numbers of resected
      lymph nodes and of metastatic lymph nodes were 17 (range 6-85) and 2 (1-36),
      respectively. Hilar (N1) and mediastinal (N2) metastases were identified in 21.3%
      and 20.0% of cases, respectively. Overall, the 5-year OS and DFS rates were 54.6%
      and 44.8%, respectively. At multivariable analysis, age, gender, pathological
      stage, R0 resection, type of surgery and NR correlated with longer OS rates; the
      same variables plus tumour grading were further related to DFS. C-statistics were
      66.0 (95% CI 62.7-69.4) for DFS and 60.5 (95% CI 58.3-62.6) for OS. An NR <40%
      significantly correlated with a higher 5-year survival rate in the total sample
      (OS 57.6% vs 23.8%, P < 0.001; DFS 48.2% vs 11.4, P < 0.001) and in patients with
      N1 (OS 47.9% vs 36.1%, P = 0.03; DFS 39% vs 24.2%, P = 0.02) and N2 (OS 36.9% vs
      21.8%, P < 0.001 DFS 23.9% vs 9.1%, P < 0.001). CONCLUSIONS: Our study confirms
      that the number of resected lymph nodes is a strong prognostic indicator in
      NSCLC. In particular, an NR cut-off value of 40% may predict both OS and DFS.

PMID- 30202954
TI  - Chronic pararenal aortic and iliac occlusion.

PMID- 30202955
TI  - Immediate and substantial evolution of T cell repertoire in peripheral blood and
      tumor microenvironment of patients with esophageal squamous cell carcinoma
      treated with preoperative chemotherapy.
AB  - Preoperative chemotherapy could decrease tumor size and improve overall survival
      for esophageal squamous cell carcinoma (ESCC), and moreover rational combination
      of chemotherapy and immunotherapy could increase likelihood of inducing an
      effective anti-tumor immune response. However, the immunologic impact of
      chemotherapeutic drugs originally chose for cancer treatment due to the direct
      toxicity is poorly understood. We assess the effect of a combination of
      clinically approved chemotherapeutic drugs (Paclitaxel-nedaplatin [PTX-NDP]) on
      TCR repertoires of peripheral T cells and TILs from five patients with primary
      ESCC. We found that PTX-NDP therapy induced immediate and substantial changes in
      clonotype frequencies of peripheral T cells and TILs and moreover compared with
      clonal amplification, clonal contraction was more likely to occur in more
      abundant clones in patients with ESCC. Significant increases of TCR diversity
      were observed in peripheral T cells but not in TILs after PTX-NDP therapy.
      Reconstruction of post-treatment TILs was not merely a result of local expansion
      or contraction of pre-treatment TILs, but also-at least in part-a consequence of
      the migration of peripheral T cells into the chronically inflamed tumor
      microenvironment. Our findings uncover further insight into T cell immune
      response modulated with chemotherapy, providing for theoretical bases for
      rational combination strategy of chemotherapy and immunotherapy.

PMID- 30202956
TI  - The CDR1as/miR-7/TGFBR2 Axis Modulates EMT in Silica-Induced Pulmonary Fibrosis.
AB  - Silicosis is one of the typical forms of pneumoconiosis characterized by abnormal
      proliferation of fibroblasts and deposition of extracellular matrix. Recent
      findings have shown that microRNAs and circular RNAs (circRNAs) are implicated in
      many diseases. However, the function of noncoding RNAs in pulmonary fibrosis
      remain to be elucidated. Here, miR-7 was found significantly decreased in silica
      treated pulmonary epithelial cells as well as in fibrotic lung tissues of mice.
      Elevated expression of miR-7 via agomir injection relieved lung fibrosis in vivo.
      Further molecular study showed that miR-7 played its role against pulmonary
      fibrosis by blocking epithelial-mesenchymal transition (EMT) progression of human
      bronchial epithelial cells and A549 cells. Notably, transforming growth factor
      beta receptor 2 (TGFBR2) was identified as a target gene of miR-7 with
      bioinformatics tools, which was verified by dual luciferase receptor gene assay
      in human bronchial epithelial cells and A549 cells. Silica induced elevation of
      TGFBR2 could be abolished by exogenous expression of miR-7. Furthermore,
      bioinformatics software indicated that circRNA CDR1as had several binding sites
      for miR-7. The inhibitory effects of miR-7 on EMT and its target TGFBR2 were
      suppressed by circRNA CDR1as, which contributed to pulmonary fibrosis. Our
      studies also revealed overexpressed miR-7 could repress fibrogenesis of lung
      fibroblasts induced by TGF-beta1. Collectively, circRNA CDR1as stimulated by
      silica could sponge miR-7 to release TGFBR2, plays an important role during
      pulmonary fibrosis by promoting EMT process. These results indicated that the
      interaction between miR-7 and circRNA CDR1as may exert important functions and
      provide potential therapeutic targets in lung fibrotic diseases.

PMID- 30202957
TI  - Improved blood flow after percutaneous transluminal septal myocardial ablation
      visualized by 4D flow cardiac magnetic resonance in a case of hypertrophic
      obstructive cardiomyopathy.

PMID- 30202958
TI  - A case of fibrosing mediastinitis complicated by pulmonary hypertension and right
      sided heart failure.

PMID- 30202959
TI  - Implementation of B'More Healthy Communities for Kids: process evaluation of a
      multi-level, multi-component obesity prevention intervention.
AB  - B'More Healthy Communities for Kids was a multi-level, multi-component obesity
      prevention intervention to improve access, demand and consumption of healthier
      foods and beverages in 28 low-income neighborhoods in Baltimore City, MD. Process
      evaluation assesses the implementation of an intervention and monitor progress.
      To the best of our knowledge, little detailed process data from multi-level
      obesity prevention trials have been published. Implementation of each
      intervention component (wholesaler, recreation center, carryout restaurant,
      corner store, policy and social media/text messaging) was classified as high,
      medium or low according to set standards. The wholesaler component achieved high
      implementation for reach, dose delivered and fidelity. Recreation center and
      carryout restaurant components achieved medium reach, dose delivered and
      fidelity. Corner stores achieved medium reach and dose delivered and high
      fidelity. The policy component achieved high reach and medium dose delivered and
      fidelity. Social media/text messaging achieved medium reach and high dose
      delivered and fidelity. Overall, study reach and dose delivered achieved a high
      implementation level, whereas fidelity achieved a medium level. Varying levels of
      implementation may have balanced the performance of an intervention component for
      each process evaluation construct. This detailed process evaluation of the B'More
      Healthy Communities for Kids allowed the assessment of implementation successes,
      failures and challenges of each intervention component.

PMID- 30202960
TI  - Leter to the Editor.

PMID- 30202961
TI  - Metagenomic sequencing provides insights into microbial detoxification in the
      guts of small mammalian herbivores (Neotoma spp.).
AB  - Microbial detoxification of plant toxins influences the use of plants as food
      sources by herbivores. Stephen's woodrats (Neotoma stephensi) specialize on
      juniper, which is defended by oxalate, phenolics and monoterpenes, while closely
      related N. albigula specialize on cactus, which only contains oxalate. Woodrats
      maintain two gut chambers harboring dense microbial communities: a foregut
      chamber proximal to the major site of toxin absorption, and a cecal chamber in
      their hindgut. We performed several experiments to investigate the location and
      nature of microbial detoxification in the woodrat gut. First, we measured toxin
      concentrations across gut chambers of N. stephensi. Compared to food material,
      oxalate concentrations were immediately lower in the foregut, while
      concentrations of terpenes remained high in the foregut, and were lowest in the
      cecal chamber. We conducted metagenomic sequencing of the foregut chambers of
      both woodrat species and cecal chambers of N. stephensi to compare microbial
      functions. We found that most genes associated with detoxification were more
      abundant in the cecal chambers of N. stephensi. However, some genes associated
      with degradation of oxalate and phenolic compounds were more abundant in the
      foregut chambers. Thus, microbial detoxification may take place in various
      chambers depending on the class of chemical compound.

PMID- 30202963
TI  - Spatial structuring of bacterial communities in epilithic biofilms in the
      Acquarossa river (Italy).
AB  - Epilithic river biofilms characterize the rock surfaces along the Acquarossa
      river (Viterbo, Italy); they are in part red and in part black colored,
      maintaining a well-defined borderline. This peculiarity has raised questions
      about the biotic and abiotic phenomena that might avoid the mixing of the two
      biofilms. In this study, the structuring of bacterial communities in black and
      red epilithic biofilm in the Acquarossa river has been investigated with both
      culture dependent and independent approaches. Data obtained highlighted a (very)
      different taxonomic composition of black and red epilithons bacterial
      communities, dominated by Acinetobacter sp. and iron-oxidizing bacteria,
      respectively. The chemical characterization of both river water and biofilms
      revealed a substantial heavy metals pollution of the environment; heavy metals
      were also differentially accumulated in red and black epilithons. Overall, our
      data revealed that the structuring of red and black epilithons might be affected
      mainly by the antagonistic interactions exhibited by bacterial genera dominating
      the two biofilms. These findings suggest that biotic factors might be responsible
      for the structuring of natural bacterial communities, suggesting that there is a
      selection of populations at very small scale, and that different populations
      might compete for different niches.

PMID- 30202964
TI  - Left ventricular assist devices: let's move toward better quality of extended
      life, away from hospital.

PMID- 30202962
TI  - Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines
      on the Evaluation and Treatment of Patients With Thoracolumbar Spine Trauma:
      Pharmacological Treatment.
AB  - QUESTION: Does the administration of a specific pharmacologic agent (eg,
      methylprednisolone) improve clinical outcomes in patients with thoracic and
      lumbar fractures and spinal cord injury? RECOMMENDATION: There is insufficient
      evidence to make a recommendation; however, the task force concluded, in light of
      previously published data and guidelines, that the complication profile should be
      carefully considered when deciding on the administration of methylprednisolone.
      Strength of recommendation: Grade Insufficient The full version of the guideline
      can be reviewed at: https://www.cns.org/guideline-chapters/congress-neurological
      surgeons-systematic-review-evidence-based-guidelines/chapter_5.

PMID- 30202965
TI  - Dr Sarah Clarke, President, British Cardiovascular Society 2015-2018.

PMID- 30202966
TI  - Sarah Clarke, Cambridge, England.

PMID- 30202968
TI  - Key presentations at the 2018 British Cardiovascular Society conference.

PMID- 30202967
TI  - Cleveland Clinic comes to London.

PMID- 30202969
TI  - Congenital heart and aortic disease: novel genetic causes, biomarkers, and effect
      of pregnancy.

PMID- 30202971
TI  - Contemplating a Career in Burn Surgery: Data From the 2016 Burn Physician Survey.
AB  - There is a paucity of information in the peer-reviewed literature characterizing
      the current burn surgeon workforce and compensation potential, and, in a parallel
      topic, training opportunities and recruitment methods. What does exist documents
      minimal exposure to the field and surgeon shortages. A comprehensive survey was
      created to address 1) the demographics of current burn surgeons in practice, and
      2) the structure of burn centers training models. Finally, three questions were
      asked regarding job satisfaction. With a response rate of 23%, demographics
      reflect representative involvement across the age spectrum. The majority of
      respondents (73.9%) had training in general surgery, with subsequent postgraduate
      training primarily in surgical critical care or burn fellowships. Two-thirds of
      respondents have active practices, cover multiple specialties, and take
      multispecialty call throughout the month. A variety of models are used to
      calculate compensation. The vast majority of burn centers train residents:
      general surgery residents (89%), plastic surgery residents (63%), and emergency
      medicine residents (32%), most of whom are in their first 3 years of training.
      The majority of respondents would become a burn surgeon again if they had to do
      it over and would recommend it to young surgeons as a career. A representative
      sample of burn surgeons from across North America sustains practices in similar
      ways. Access to the next generation of surgeons is at an early period in training
      (PGY1-3) which may prove valuable as surgical education evolves. Overall, burn
      surgeons express good job satisfaction, a significant point of interest as
      attention turns towards succession planning.

PMID- 30202972
TI  - Screening for Pfhrp2/3-Deleted Plasmodium falciparum, Non-falciparum, and Low
      Density Malaria Infections by a Multiplex Antigen Assay.
AB  - Background: Detection of Plasmodium antigens provides evidence of malaria
      infection status and is the basis for most malaria diagnosis worldwide. Methods:
      We developed a sensitive bead-based multiplex assay for laboratory use which
      simultaneously detects the pan-Plasmodium pAldo, pan-Plasmodium pLDH, and P.
      falciparum PfHRP2 antigens. The assay was validated against purified recombinant
      antigens, mono-species malaria infections, and non-infected blood samples. To
      test against samples collected in an endemic setting, Angolan outpatient samples
      (n=1267) were assayed. Results: Of 466 Angolan samples positive for at least one
      antigen, the most common antigen profiles were PfHRP2+/pAldo+/pLDH+ (167, 36%),
      PfHRP2+/pAldo-/pLDH- (163, 35%), and PfHRP2+/pAldo+/pLDH- (129, 28%). Antigen
      profile was predictive of qRT-PCR positivity and parasite density. Eight Angolan
      samples (1.7%) had either no or very low levels of PfHRP2 but were positive for
      one or both of the other antigens. PCR analysis confirmed three (0.6%) were P.
      ovale infections, and two (0.4%) represented P. falciparum parasites lacking
      Pfhrp2 and/or Pfhrp3. Conclusions: These are the first reports of P. falciparum
      Pfhrp2/3 deletion mutants in Angola. High-throughput multiplex antigen detection
      can inexpensively screen for low density P. falciparum, non-falciparum, and
      Pfhrp2/3-deleted malaria parasites to provide population-level antigen estimates
      and identify specimens requiring further molecular characterization.

PMID- 30202970
TI  - Metagenomic Analysis of Fish-Associated Ca. Parilichlamydiaceae Reveals Striking
      Metabolic Similarities to the Terrestrial Chlamydiaceae.
AB  - Chlamydiae are an example of obligate intracellular bacteria that possess highly
      reduced, compact genomes (1.0-3.5 Mbp), reflective of their abilities to
      sequester many essential nutrients from the host that they no longer need to
      synthesize themselves. The Chlamydiae is a phylum with a very wide host range
      spanning mammals, birds, fish, invertebrates, and unicellular protists. This
      ecological and phylogenetic diversity offers ongoing opportunities to study
      intracellular survival and metabolic pathways and adaptations. Of particular
      evolutionary significance are Chlamydiae from the recently proposed Ca.
      Parilichlamydiaceae, the earliest diverging clade in this phylum, species of
      which are found only in aquatic vertebrates. Gill extracts from three
      Chlamydiales-positive Australian aquaculture species (Yellowtail kingfish,
      Striped trumpeter, and Barramundi) were subject to DNA preparation to deplete
      host DNA and enrich microbial DNA, prior to metagenome sequencing. We assembled
      chlamydial genomes corresponding to three Ca. Parilichlamydiaceae species from
      gill metagenomes, and conducted functional genomics comparisons with diverse
      members of the phylum. This revealed highly reduced genomes more similar in size
      to the terrestrial Chlamydiaceae, standing in contrast to members of the
      Chlamydiae with a demonstrated cosmopolitan host range. We describe a reduction
      in genes encoding synthesis of nucleotides and amino acids, among other
      nutrients, and an enrichment of predicted transport proteins. Ca.
      Parilichlamydiaceae share 342 orthologs with other chlamydial families. We
      hypothesize that the genome reduction exhibited by Ca. Parilichlamydiaceae and
      Chlamydiaceae is an example of within-phylum convergent evolution. The factors
      driving these events remain to be elucidated.

PMID- 30202973
TI  - Prostaglandin E2-mediated impairment of innate immune response to A(H1N1)pdm09
      infection in diet-induced obese mice could be restored by paracetamol.
AB  - Objective: To investigate why obesity leads to increased severity of influenza
      infection. Methods: We employed a mouse model with diet-induced obesity (DIO) to
      study the innate immune responses induced by influenza virus. Results: The lungs
      of DIO mice were heavily affected by obesity-associated chronic systemic
      inflammation with a significant increase in inflammatory cytokines/chemokines.
      Concurrently, lipid immune mediator prostaglandin E2 (PGE2) was also
      significantly elevated in DIO mice. However, the DIO mice mounted a blunted and
      delayed upregulation of mRNA and protein concentrations of interferon-beta and
      inflammatory cytokines/chemokines upon A(H1N1)pdm09 virus (H1N1/415742Md)
      challenge comparing with those of lean mice. PGE2 concentrations were
      significantly higher in the lungs of DIO mice comparing to that of lean mice post
      challenge. Treatment with paracetamol in challenged DIO mice significantly
      enhanced the expression of interferon-alpha/beta and cytokine genes at days 1 and
      3 post infection comparing with that of untreated DIO mice. Furthermore,
      paracetamol treatment alone started 3 days before virus challenge and continued
      till 6 days post-challenge, ameliorated the severity of a lethal H1N1/415742Md
      infection in DIO mice with improved survival. Conclusions: Impaired innate
      response to influenza in DIO mice is associated with elevated PGE2, which could
      be restored to some degree by paracetamol treatment.

PMID- 30202974
TI  - Behcet's disease as a cause of cerebral sinus vein thrombosis: an emerging role.

PMID- 30202975
TI  - Surgical results of total anomalous pulmonary venous connection repair in 256
      patients.
AB  - OBJECTIVES: This study was performed to analyse the surgical results of total
      anomalous pulmonary venous connection (TAPVC) repair at a single institution and
      to identify trends and variables associated with mortality and morbidity,
      particularly predictors of recurrent pulmonary venous obstruction (PVO). METHODS:
      Our surgical database contained 256 patients with biventricular anatomy who
      underwent surgical repair for TAPVC from 1981 to 2016. The anatomic TAPVC
      subtypes in this study were as follows: 114 supracardiac (44.5%), 56 cardiac
      (21.9%), 64 infracardiac (25.0%) and 22 mixed (8.6%) types. The follow-up for the
      entire study ranged from 1.6 months to 28.2 years (median 10.4 years).
      Preoperative PVO was present in 128 patients (50.0%). All patients with TAPVC
      with single-ventricle anatomy were excluded from the analysis. Data were
      retrospectively reviewed. RESULTS: Seven (2.7%) early deaths and 26 (10.1%) late
      deaths occurred. The actuarial survival rate at 20 years postoperatively was
      85.3%. The preoperative predictors of operative mortality were younger age and
      the era of TAPVC repair (before 1998). In addition to these variables, associated
      cardiac anomalies were predictors of late mortality. Those for postoperative PVO
      were younger age, lower weight and being an emergency case. The actuarial
      survival rate at 20 years was 38.6% for patients with postoperative PVO and 92.2%
      for patients without postoperative PVO (P < 0.001). CONCLUSIONS: The long-term
      outcomes after TAPVC repair in patients with biventricular anatomy were
      satisfactory. Mortality was significantly associated with the rate of progression
      of postoperative PVO, and careful follow-up was required especially within 6
      months after the primary operation.

PMID- 30202976
TI  - Surgical removal of an inferior vena cava filter with duodenal penetration.
AB  - Complications due to long-term implantation of inferior vena cava (IVC) filters
      have increased. Among these, IVC wall penetration by struts can lead to
      penetration of adjacent structures, which can be fatal to the patient. Herein, we
      report a case of a 63-year-old woman who underwent surgical removal of an IVC
      filter with duodenal penetration. Oesophagogastroduodenoscopy findings revealed a
      strut in the duodenal second portion. The IVC filter was inserted 19 months ago
      but had not been retrieved. On admission, computed tomography showed malposition
      of the IVC filter with penetration of duodenum by an anterior strut. Therefore,
      we performed surgical removal of the IVC filter. After surgery, her postoperative
      course was uneventful.

PMID- 30202977
TI  - Stakeholder expectations, roles and responsibilities in Dutch health promotion
      for people with intellectual disabilities.
AB  - This two-phase, qualitative study aims to obtain an overview of stakeholders in
      the network of people with intellectual disabilities (ID) and their perceived
      facilitating and hindering factors, expectations, and perceived roles and
      responsibilities with regard to health promotion. In phase 1, four workshops were
      conducted to provide insight into involved stakeholders. In phase 2, 29 semi
      structured interviews were conducted with stakeholders regarding their views on
      health promotion. Data were analysed using stakeholder matrices and a combination
      of domain and thematic analysis. Daily caregivers were identified as the most
      important and influential stakeholders. Interviewed stakeholders perceived
      barriers to a healthy lifestyle as relating mainly to the person with ID and,
      although they stated that people with ID need support to be able to live
      healthily, there was ambiguity about roles and responsibilities for providing
      this support. Daily caregivers are not properly facilitated to support a healthy
      lifestyle. Stakeholders expressed the need for a culture change towards a greater
      health promotion ethos in care for people with ID. A facilitating context is
      needed in which the social network supports autonomy and offers opportunities to
      adapt to physical, social and emotional challenges. Stakeholders see the
      importance of, and are willing to support, healthy behaviour. They are hindered
      by a lack of a shared vision and united system in which all stakeholders know
      their roles and responsibilities. Promotion of a healthy lifestyle should be part
      of every service provider employee's job and propagated throughout the
      organization as part of its mission and vision.

PMID- 30202978
TI  - Response to Letter to the Editor (Effectiveness of Prenatal Vitamin D Deficiency
      Screening and Treatment Program: A Stratified Randomized Field Trial).

PMID- 30202979
TI  - Cotton CENTRORADIALIS/TERMINAL FLOWER 1/SELF-PRUNING genes functionally diverged
      to differentially impact plant architecture.
AB  - Genes of the CENTRORADIALIS/TERMINAL FLOWER 1/SELF-PRUNING (CETS) family
      influence meristem identity by controlling the balance between indeterminate and
      determinate growth, thereby profoundly impacting plant architecture. Artificial
      selection during cotton (Gossypium hirsutum) domestication converted
      photoperiodic trees to the day-neutral shrubs widely cultivated today. To
      understand the regulation of cotton architecture and exploit these principles to
      enhance crop productivity, we characterized the CETS gene family from tetraploid
      cotton. We demonstrate that genes of the TERMINAL FLOWER 1 (TFL1)-like clade show
      different roles in regulating growth patterns. Cotton has five TFL1-like genes:
      SELF-PRUNING (GhSP) is a single gene whereas there are two TFL1-like and BROTHER
      OF FT (BFT)-like genes, and these duplications are specific to the cotton
      lineage. All genes of the cotton TFL1-like clade delay flowering when ectopically
      expressed in transgenic Arabidopsis, with the strongest phenotypes failing to
      produce functional flowers. GhSP, GhTFL1-L2, and GhBFT-L2 rescue the early
      flowering Attfl1-14 mutant phenotype, and the encoded polypeptides interact with
      a cotton FD protein. Heterologous promoter::GUS fusions illustrate differences in
      the regulation of these genes, suggesting that genes of the GhTFL1-like clade may
      not act redundantly. Characterizations of the GhCETS family provide strategies
      for nuanced control of plant growth.

PMID- 30202982
TI  - Klebsiella pneumoniae type VI secretion system contributes to bacterial
      competition, cell invasion, type-1 fimbriae expression, and in vivo colonization.
AB  - Background: We previously isolated a Klebsiella pneumoniae strain, NTUH-K2044,
      from a community-acquired pyogenic liver abscess (PLA) patient. Analysis of the
      NTUH-K2044 genome revealed that this strain harbors two putative type VI
      secretion system (T6SS)-encoding gene clusters. Methods: The distribution of T6SS
      genes in the PLA and intestinal-colonizing K. pneumoniae clinical isolates was
      examined. icmF1-, icmF2-, icmF1/icmF2- and hcp-deficient K pneumoniae strains
      were constructed using an unmarked deletion method. The roles of T6SSs in
      antibacterial activity, type-1 fimbriae expression, cell adhesion and invasion
      and intestinal colonization were determined. Results: The prevalence of T6SSs is
      higher in the PLA strains than in the intestinal-colonizing strains (37/42 vs.
      54/130). Deletion of icmF1/icmF2 and hcp genes significantly reduced
      interbacterial and intrabacterial killing. Strain deleted for icmF1 and icmF2
      exhibited decreased transcriptional expression of type-1 fimbriae and reduced
      adherence to and invasion of human colorectal epithelial cells, and was
      attenuated for in vivo competition to enable colonization of the host gut.
      Lastly, Hcp expression in K. pneumoniae was silenced by the histone-like nucleoid
      structuring protein via direct binding. Conclusions: These results provide new
      insights into T6SS-mediated bacterial competition and attachment in K.
      pneumoniae, and could facilitate the prevention of K. pneumoniae infection.

PMID- 30202980
TI  - PLK1 targets CtIP to promote microhomology-mediated end joining.
AB  - Proper DNA double-strand break (DSB) repair is essential for maintaining genome
      integrity. Microhomology-mediated end joining (MMEJ) is an error-prone repair
      mechanism, which introduces mutations at break sites and contributes to
      chromosomal translocations and telomere fusions, thus driving carcinogenesis.
      Mitotic kinases PLK1, CDK1 and Aurora A are important for supporting MMEJ and are
      often overexpressed in various tumors. However, the functional interplay between
      these kinases and MMEJ has not been explored. Here, we found that MMEJ is
      preferentially employed to fix DSBs in cells arrested in mitosis following
      nocodazole treatment. We further showed that the DSB repair factor CtIP is
      jointly phosphorylated by CDK1/Aurora A and PLK1. CDK1/Aurora A-mediated CtIP
      phosphorylation at serine 327 triggers CtIP binding to the PLK1 polo-box domain,
      which in turn facilitates PLK1 to phosphorylate CtIP mainly at serine 723. A PLK1
      phosphor-mimic CtIP mutant fails to initiate extended end resection and is thus
      unable to mediate homologous recombination and the G2/M checkpoint but can
      mediate MMEJ. These data imply that PLK1 may target CtIP to promote error-prone
      MMEJ and inactivate the G2/M checkpoint. These findings have helped elucidate the
      oncogenic roles of these factors.

PMID- 30202983
TI  - Nature of Long-Range Evolutionary Constraint in Enzymes: Insights from Comparison
      to Pseudoenzymes with Similar Structures.
AB  - Enzymes are known to fine-tune their sequences to optimize catalytic function,
      yet quantitative evolutionary design principles of enzymes remain elusive on the
      proteomic scale. Recently, it was found that the catalytic site in enzymes
      induces long-range evolutionary constraint, where even sites distant to the
      catalytic site are more conserved than expected. Given that protein-fold usage is
      generally different between enzymes and nonenzymes, it remains an open question
      to what extent this long-range evolutionary constraint in enzymes is dictated,
      either directly or indirectly, by the special three-dimensional structure of the
      enzyme. To investigate this question, we have compared evolutionary properties of
      enzymes with those of counterpart pseudoenzymes that share the same protein fold
      but are catalytically inactive. We found that the long-range evolutionary
      constraint observed in enzymes is significantly reduced in pseudoenzyme
      counterparts, despite very high structural similarity (~1.5 A RMSD on average).
      Furthermore, this significant reduction in long-range evolutionary constraint is
      observed even in pseudoenzyme counterparts which retain the ligand-binding
      ability of enzymes. Finally, the distance between the site that induces the
      highest gradient of sequence conservation and the pseudocatalytic site in
      pseudoenzymes is significantly larger than the corresponding distance in enzymes.
      Taken together, our results suggest that the long-range evolutionary constraint
      in enzymes is induced mainly by the presence of the catalytic site rather than by
      the special three-dimensional structure of the enzyme, and that such long-range
      evolutionary constraint in enzymes depends mainly on the catalytic function of
      the active site rather than on the ligand-binding ability of the enzyme.

PMID- 30202981
TI  - Uraemia-induced immune senescence and clinical outcomes in chronic kidney disease
      patients.
AB  - Background: Patients with chronic kidney disease (CKD) are more prone to develop
      premature age-related diseases. Data on immune senescence are scarce in CKD
      populations, except in end-stage renal disease and dialysis. We designed a
      longitudinal prospective study to evaluate immune senescence at different CKD
      stages and its influence on CKD patient outcomes. Methods: Clinical and
      biological data collections were performed on 222 patients at different CKD
      stages [1-2 (n = 85), 4 (n = 53) and 5 (n = 84)]. Immune senescence biomarkers
      were measured by cytometry on T cells (CD28, CD57, CD45RA, CD31, gammaH2A.X) or
      by quantitative polymerase chain reaction [relative telomere length (RTL)] on
      peripheral blood mononuclear cells and analysed according to CKD stages and
      outcomes. Results: CKD was associated with an increase in immune senescence and
      inflammation biomarkers, as follows: low thymic output (197 +/- 25 versus 88 +/-
      13 versus 73 +/- 21 CD4+CD45RA+CD31+ T cells/mm3), an increased proportion of
      terminally differentiated T cells (CD8+CD28-CD57+) (24 +/- 18 versus 32 +/- 17
      versus 35 +/- 19%) restricted to cytomegalovirus-positive patients, telomere
      shortening (1.11 +/- 0.36 versus 0.78 +/- 0.24 versus 0.97 +/- 0.21
      telomere:single copy ratio) and an increase in C-reactive protein levels [median
      2.9 (range 1.8-4.9) versus 5.1 (27-9.6) versus 6.2 (3.4-10.5) mg/L]. In
      multivariate analysis, shorter RTL was associated with death {hazard ratio [HR]
      4.12 [95% confidence interval (CI) 1.44-11.75]}. Low thymic output was associated
      with infections [HR 1.79 (95% CI (1.34-9.58)] and terminally differentiated CD8+
      T-cell expansion with a risk of cardiovascular events [CEs; HR 4.86 (95% CI 1.72
      13.72)]. Conclusion: CKD was associated with premature immune ageing. Each of
      these alterations increased the risk of specific age-related diseases, such as
      RTL and death, thymic function and infections and terminally differentiated CD8+
      T-cell expansion and CEs.

PMID- 30202984
TI  - Seropositivity to multiple anogenital HPV types is associated with current
      anogenital HPV infection, abnormal cytology and seropositivity for non-genital
      HPVs.
AB  - Background: Antibodies against human papillomaviruses (HPV) are biomarkers for
      current or past infections. We assessed whether antibodies against multiple HPV
      types were determinants of current multiple anogenital HPV infections, abnormal
      cytology and seropositivity for cutaneous HPVs. Methods: 1,848 Slovenian women
      attended two rounds of cervical cancer screening three years apart and provided
      data on HPV antibodies and HPV DNA at both visits. Antibodies against 15
      anogenital HPV types and 6 cutaneous HPVs were determined using pseudovirion
      luminex serology and anogenital HPV DNA using Linear Array. Antibodies to
      polyomaviruses were evaluated as a control. Women were grouped as either HPV
      seronegative, having antibodies to 1-2 HPV types or to >= 3 HPV types. Results:
      Presence of antibodies to multiple anogenital HPV types at baseline was
      associated strongly with (i) presence of HPV DNA at the cervix
      (chi2=68.8;p<0.0001), (ii) multiple types of HPV DNA at baseline (chi2=58.6;
      p<0.0001), (iii) HPV DNA at follow-up (chi2= 22.9; p<0.0001) (iv) abnormal
      cytology (chi2=9.8; p=0.0017), (v) concomitant presence of antibodies to any of
      six non-genital HPV types (chi2=40.1;p<0.0001). Presence of antibodies to >=3
      anogenital HPV types tended to persist over time. Conclusions: Seropositivity
      against at least 3 anogenital HPV types is associated with current multiple
      anogenital HPV infections, abnormal cytology and seropositivity to non-genital
      HPVs.

PMID- 30202986
TI  - Improved Cosmetic Outcome With Bilateral Paraspinal Muscle Flap Closure Following
      Cervical Laminectomy and Fusion.
AB  - BACKGROUND: Poor cosmetic results following cervical laminectomy and fusion (CLF)
      are rarely considered in assessing surgical complications. Atrophy from muscle
      denervation and posterior bone loss may result in a sunken appearance; relative
      tension may lead to wide, unsightly scars. Paraspinal muscle flaps are routinely
      employed by plastic surgeons for closure of wound infection and dehiscence.
      OBJECTIVE: To assess clinical and cosmetic results of CLF with/without a
      paraspinal muscle flap closure technique. METHODS: A retrospectively collected
      cohort analysis was undertaken for a 12-yr period in CLF patients. During the
      study period, a paraspinal muscle flap closure technique was adopted. Wounds were
      inspected for scar width and depth using a scale devised to categorize the
      posterior neck contour. Minimum follow-up was 12 mo. RESULTS: Of 159 patients, 94
      wounds were evaluated of which 34 had muscle flap closure. There were no
      differences in age, sex, body mass index, mJOA scores, diabetes status, or number
      of spinal levels treated. Mean follow-up was 18.6 (12-48) and 49.8 (12-130) mo in
      the muscle flap and conventional closure groups respectively; contour scores were
      1.20 vs 2.65 (P < .00001) and scar width was 2.8 vs 4.9 mm (P < .0001). No
      patient had a wound complication in the muscle flap group and 4 (7%) in the
      conventional closure group. CONCLUSION: Paraspinal muscle flap closure of CLF
      improved cosmetic appearance in terms of wound contour and scar width. Further
      investigation is needed to determine any effect upon wound infection and
      dehiscence rates.

PMID- 30202987
TI  - Factors Associated with Prescription Opioid Analgesic Use in the US Population,
      2011-2014.
AB  - Objective: This study examined factors associated with prescription opioid
      analgesic use in the US population using data from a nationally representative
      sample. It focused on factors previously shown to be associated with opioid use
      disorder or overdose. Variations in the use of different strength opioid
      analgesics by demographic subgroup were also examined. Methods: Data came from
      respondents aged 16 years and older who participated in the National Health and
      Nutrition Examination Survey (2011-2014). Respondents were classified as opioid
      users if they reported using one or more prescription opioid analgesics in the
      past 30 days. Results: Opioid users reported poorer self-perceived health than
      those not currently using opioids. Compared with those not using opioids, opioid
      users were more likely to rate their health as being "fair" or "poor" (40.4% [95%
      confidence interval {CI} = 34.9%-46.2%] compared with 15.6% [95% CI = 14.3%
      17.1%]), experienced more days of pain during the past 30 days (mean = 14.3 [95%
      CI = 12.9-15.8] days compared with 2.3 [95% CI = 2.0-2.7] days), and had
      depression (22.5% [95% CI = 17.3%-28.7%] compared with 7.1% [95% CI = 6.2%
      8.0%]). Among those who reported using opioids during the past 30 days, 18.8%
      (95% CI = 14.4%-24.1%) reported using benzodiazepine medication during the same
      period and 5.2% (95% CI = 3.5%-7.7%) reported using an illicit drug during the
      past six months. When opioid strength was examined, a smaller percentage of
      adults aged 60 years and older used stronger-than-morphine opioids compared with
      adults aged 20-39 and 40-59 years. Conclusions: Higher percentages of current
      opioid users than nonusers reported having many of the factors associated with
      opioid use disorder and overdose.

PMID- 30202985
TI  - Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines
      on the Evaluation and Treatment of Patients with Thoracolumbar Spine Trauma:
      Executive Summary.
AB  - BACKGROUND: The thoracic and lumbar ("thoracolumbar") spine are the most commonly
      injured region of the spine in blunt trauma. Trauma of the thoracolumbar spine is
      frequently associated with spinal cord injury and other visceral and bony
      injuries. Prolonged pain and disability after thoracolumbar trauma present a
      significant burden on patients and society. OBJECTIVE: To formulate evidence
      based clinical practice recommendations for the care of patients with injuries to
      the thoracolumbar spine. METHODS: A systematic review of the literature was
      performed using the National Library of Medicine PubMed database and the Cochrane
      Library for studies relevant to thoracolumbar spinal injuries based on specific
      clinically oriented questions. Relevant publications were selected for review.
      RESULTS: For all of the questions posed, the literature search yielded a total of
      6561 abstracts. The task force selected 804 articles for full text review, and 78
      were selected for inclusion in this overall systematic review. CONCLUSION: The
      available evidence for the evaluation and treatment of patients with
      thoracolumbar spine injuries demonstrates considerable heterogeneity and highly
      variable degrees of quality. However, the workgroup was able to formulate a
      number of key recommendations to guide clinical practice. Further research is
      needed to counter the relative paucity of evidence that specifically pertains to
      patients with only thoracolumbar spine injuries. The full version of the
      guideline can be reviewed at: https://www.cns.org/guideline-chapters/congress
      neurological-surgeons-systematic-review-evidence-based-guidelines/chapter_1.

PMID- 30202988
TI  - Relative prognostic impact of nutrition, anaemia, bone metabolism and
      cardiovascular comorbidities in elderly haemodialysis patients.
AB  - Background: The prognostic impact of nutrition and chronic kidney disease (CKD)
      complications has already been described in elderly haemodialysis patients but
      their relative weights on risk of death remain uncertain. Using structural
      equation models (SEMs), we aimed to model a single variable for nutrition, each
      CKD complication and cardiovascular comorbidities to compare their relative
      impact on elderly haemodialysis patients' survival. Methods: This prospective
      study recruited 3165 incident haemodialysis patients >=75 years of age from 178
      French dialysis units. Using SEMs, the following variables were computed:
      nutritional status, anaemia, mineral and bone disorder and cardiovascular
      comorbidities. Systolic blood pressure was also used in the analysis. Survival
      analyses used Poisson models. Results: The population average age was 81.9 years
      (median follow-up 1.51 years, 35.5% deaths). All variables were significantly
      associated with mortality by univariate analysis. Nutritional status was the
      variable most strongly associated with mortality in the multivariate analysis,
      with a negative prognostic impact of low nutritional markers {incidence rate
      ratio [IRR] 1.42 per 1 standard deviation [SD] decrement [95% confidence interval
      (CI) 1.32-1.53]}. The 'cardiovascular comorbidities' variable was the second
      variable associated with mortality [IRR 1.19 per 1 SD increment (95% CI 1.11
      1.27)]. A trend towards low intact parathyroid hormone and high serum calcium and
      low values of systolic blood pressure were also associated with poor survival.
      The variable 'anaemia' was not associated with survival. Conclusions: These
      findings should help physicians prioritize care in elderly haemodialysis patients
      with CKD complications, with special focus on nutritional status.

PMID- 30202989
TI  - Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines
      on the Evaluation and Treatment of Patients With Thoracolumbar Spine Trauma:
      Radiological Evaluation.
AB  - BACKGROUND: Radiological evaluation of traumatic thoracolumbar fractures is used
      to classify the injury and determine the optimal treatment plan. Currently, there
      remains a lack of consensus regarding appropriate radiological protocol. Most
      clinicians use a combination of plain radiographs, 3-dimensional computed
      tomography with reconstructions, and magnetic resonance imaging (MRI). OBJECTIVE:
      To determine, through evidence-based guidelines review: (1) whether the use of
      MRI to identify ligamentous integrity predicted the need for surgical
      intervention; and (2) if there are any radiological findings that can assist in
      predicting clinical outcomes. METHODS: A systematic review of the literature was
      performed using the National Library of Medicine/PubMed database and the Cochrane
      Library for studies relevant to thoracolumbar trauma. Clinical studies
      specifically addressing the radiological evaluation of thoracolumbar spine trauma
      were selected for review. RESULTS: Two of 2278 studies met inclusion criteria for
      review. One retrospective review (Level III) and 1 prospective cohort (Level III)
      provided evidence that the addition of an MRI scan in acute thoracic and
      thoracolumbar trauma can predict the need for surgical intervention. There was
      insufficient evidence that MRI can help predict clinical outcomes in patients
      with acute traumatic thoracic and thoracolumbar spine injuries. CONCLUSION: This
      evidence-based guideline provides a Grade B recommendation that radiological
      findings in patients with acute thoracic or thoracolumbar spine trauma can
      predict the need for surgical intervention. This evidence-based guideline
      provides a grade insufficient recommendation that there is insufficient evidence
      to determine if radiographic findings can assist in predicting clinical outcomes
      in patients with acute thoracic and thoracolumbar spine injuries. QUESTION 1: Are
      there radiographic findings in patients with traumatic thoracolumbar fractures
      that can predict the need for surgical intervention? RECOMMENDATION 1: Because
      MRI has been shown to influence the management of up to 25% of patients with
      thoracolumbar fractures, providers may use MRI to assess posterior ligamentous
      complex integrity, when determining the need for surgery. Strength of
      Recommendation: Grade B. QUESTION 2: Are there radiographic findings in patients
      with traumatic thoracolumbar fractures that can assist in predicting clinical
      outcomes? RECOMMENDATION 2: Due to a paucity of published studies, there is
      insufficient evidence that radiographic findings can be used as predictors of
      clinical outcomes in thoracolumbar fractures. Strength of Recommendation: Grade
      Insufficient The full version of the guideline can be reviewed at:
      https://www.cns.org/guideline-chapters/congress-neurological-surgeons-systematic
      review-evidence-based-guidelines/chapter_3.

PMID- 30202990
TI  - ChIPprimersDB: a public repository of verified qPCR primers for chromatin
      immunoprecipitation (ChIP).
AB  - Chromatin immunoprecipitation (ChIP) has ushered in a new era of scientific
      discovery by allowing new insights into DNA-protein interactions. ChIP is used to
      quantify enriched genomic regions using qPCR, and more recently is combined with
      next generation sequencing (ChIP-seq) to obtain a genome wide profile of protein
      binding sites. Nevertheless, ChIP-qPCR remains an integral component of this
      technology for quality control purposes, before the library preparation and
      sequencing steps. In addition, ChIP-qPCR remains more time- and cost-effective
      for many focused projects in which the DNA regions of interest are already known.
      However, the DNA oligonucleotide primers needed for ChIP-qPCR are more
      challenging to design than for other qPCR projects. Here, we present the first
      public repository for ChIP oligonucleotides that have been verified to perform
      well in ChIP-qPCR experiments. ChIPprimersDB was developed by manual screening of
      publications to ensure primer quality and provide additional specific information
      on the ChIP experiments where the primers have been used. In addition to the
      primer sequences, the database includes information about the antibody, cells and
      tissues used in the experiment, information on the experimental design, and a
      direct link to the original publication. The database is linked at
      https://umiamihealth.org/bascom-palmer-eye-institute/research/clinical-and
      laboratory-research/ocular-oncology-laboratory/chip-primers and hosted at
      https://www.chipprimers.com/.

PMID- 30202992
TI  - Impact of RSV Coinfection on Human Bocavirus in Children with Acute Respiratory
      Infections.
AB  - Objective: The objective of this study was to assess epidemiological and clinical
      features of human bocavirus (HBoV) coinfection with other viruses. Method:
      Children coinfected with HBoV between January 2012 and December 2014 were
      enrolled and retrospectively reviewed. Result: A total of 984 patients were
      stratified into five groups: HBoV infection alone (n = 249), respiratory
      syncytial virus (RSV) infection alone (n = 649), HBoV coinfection with RSV (n =
      28), with human rhinovirus (HRV) (n = 39) and with other virus (n = 19). Length
      of hospitalization was longer in HBoV coinfection with RSV group than HBoV (9.0
      days vs. 7.0 days, p = 0.001), RSV (9.0 days vs. 8.0 days, p = 0.016) infection
      alone group. Pneumonia was more common in the HBoV coinfection with RSV group
      compared with the HBoV, RSV infection alone group, respectively (75.0% vs. 44.2%,
      31.3%, p < 0.001). HBoV DNA copy numbers (383 000 copies/ml) were positively
      correlated with the length of hospitalization (r = 0.334, p < 0.001). Conclusion:
      HBoV coinfection with RSV increases HBoV infection severity.

PMID- 30202991
TI  - Association of the oxytocin receptor gene with attitudinal trust: role of
      amygdala volume.
AB  - Previous studies have shown that genetic variations in rs53576, a common variant
      of the oxytocin receptor gene (OXTR) resulting from a single nucleotide
      polymorphism involving an adenine (A)/guanine (G) transition, are associated with
      attitudinal trust in men. However, the pathway from gene to behaviour has not
      been elucidated. We conducted the present study to determine whether amygdala
      volume mediates the association between OXTR rs53576 genotypes and attitudinal
      trust. Our results revealed that the left amygdala volume was significantly
      smaller in GG men than in AA and AG men, whereas it was significantly smaller in
      AA and AG women than in GG women. In addition, the left amygdala volume was
      negatively associated with attitudinal trust in men, whereas there was no such
      association in women. We also found a significant mediation effect of the left
      amygdala volume on the association between OXTR rs53576 genotypes and attitudinal
      trust in men. The results of our study suggest that the left amygdala volume
      plays a pivotal role in the association between OXTR rs53576 genotypes and
      attitudinal trust in men.

PMID- 30202994
TI  - Genome-Wide Variants Shared Between Smoking Quantity and Schizophrenia on 15q25
      Are Associated With CHRNA5 Expression in the Brain.
AB  - Cigarette smokers with schizophrenia consume more cigarettes than smokers in the
      general population. Schizophrenia and smoking quantity may have shared genetic
      liability. Genome-wide association studies (GWASs) of schizophrenia and smoking
      quantity have highlighted a biological pleiotropy in which a robust 15q25 locus
      affects both traits. To identify the genetic variants shared between these traits
      on 15q25, we used summary statistics from large-scale GWAS meta-analyses of
      schizophrenia in the Psychiatric Genomics Consortium 2 and smoking quantity
      assessed by cigarettes smoked per day in the Tobacco and Genetics Consortium. To
      evaluate the regulatory potential of the shared genetic variants, expression
      quantitative trait loci analysis in 10 postmortem brain regions was performed
      using the BRAINEAC dataset in 134 neuropathologically normal individuals. Twenty
      two genetic variants on 15q25 were associated with both smoking quantity and
      schizophrenia at the genome-wide significance level (P < 5.00 * 10-8). Major
      alleles of all variants were associated with higher smoking quantity and risk of
      schizophrenia. These genetic variants were associated with PSMA4, CHRNA3, and
      CHRNB4 expression in specific brain regions (lowest P = 4.81 * 10-4) and with
      CHRNA5 expression in multiple brain regions (lowest P = 8.70 * 10-6). Risk
      associated major alleles of these variants were commonly associated with higher
      expression in several brain regions, excluding the medulla, at the transcript
      level. In addition, the risk-associated major allele at rs637137 was associated
      with higher CHRNA5 expression at the specific exon level in multiple brain
      regions (lowest P = 2.37 * 10-5). Our findings suggest that genome-wide variants
      shared between smoking quantity and schizophrenia contribute to a common
      pathophysiology underlying these traits involving altered CHRNA5 expression in
      the brain.

PMID- 30202993
TI  - Chimeric mice with humanized livers demonstrate human-specific hepatotoxicity
      caused by a therapeutic antibody against TRAIL-receptor 2/death receptor 5.
AB  - The activation of tumor necrosis factor (TNF)-related apoptosis-inducing ligand
      receptor 2 (TRAIL-R2)/death receptor 5 (DR5) induces apoptosis in various tumor
      cells but not in normal human cells. Since some therapeutic antibodies targeting
      TRAIL-R2 have demonstrated severe hepatotoxicity in clinical applications, novel
      in vivo models reflecting clinical hepatotoxicity are now required. In this
      study, we investigated the hepatotoxicity caused by KMTR2, an anti-human TRAIL-R2
      monoclonal antibody, in chimeric mice with humanized livers (PXB-mice). PXB-mice
      were exposed to KMTR2 by single or repeated (weekly for 4 weeks) intravenous
      administrations, and the analyses of blood chemistry, liver histopathology,
      hepatic gene expression, and toxicokinetics were performed. Treatment with 1 or
      10 mg/kg of KMTR2 increased alanine transaminase (ALT) activity and human ALT1
      levels in blood. Histopathological analysis revealed that cell death and
      degeneration with the infiltration of inflammatory cells in human but not mouse
      hepatocytes were increased in a time-dependent manner after KMTR2 administration.
      Furthermore, increases in TdT-mediated dUTP nick end labeling (TUNEL)-positive
      human hepatocytes and serum concentration of cleaved cytokeratin 18, a human
      specific apoptosis marker, were observed. RNA sequence analysis showed that the
      gene expression profile changed in different manners between human and mouse
      hepatocytes and the up-regulation of TRAIL-R2-related genes was observed only in
      human hepatocytes. Taken together, these results indicate that KMTR2-mediated
      TRAIL-R2 activation induces apoptosis of human hepatocytes and hepatotoxicity in
      PXB-mice and suggest that chimeric mice with humanized liver can be novel tools
      for the evaluation of in vivo human-specific hepatotoxicity induced by
      therapeutic antibodies in pre-clinical studies.

PMID- 30202995
TI  - Treatment Strategy of a Patient With a Brain Arteriovenous Malformation and
      Cranial Dural Fistula: 2-Dimensional Operative Video.
AB  - We present the case of a 56-yr-old right-handed male, after informed consent was
      obtained, who presented with acute confusion and agitation, on the background of
      a remote history of an uncomplicated resection of a left parietal grade 2 glioma.
      Imaging revealed a large, acute right temporal intracerebral hemorrhage (ICH).
      Standard vascular workup for the cause of the ICH included catheter angiography.
      No direct cause of the hemorrhage was revealed; however, a high grade
      parasagittal dural arteriovenous fistula (DAVF) with cortical venous reflux was
      noted close to the prior craniotomy site. The venous reflux was towards the left
      hemisphere, but it was hypothesized that similar reflux on the right side may
      have been present and was not presently evident due to thrombosis. The DAVF was
      embolized by endovascular means, followed by evacuation of the hematoma. Follow
      up angiogram 7 mo later revealed a high-flow, right superior temporal cortical
      arteriovenous malformation (AVM). The DAVF unfortunately had also progressed.
      Endovascular occlusion of both lesions was attempted but was not successful.
      Subsequently, microsurgical resection for both the vascular malformations was
      performed with careful pre- and intraoperative planning to obtain a successful
      clinical and angiographic result. In this video, we summarize diagnostic and
      therapeutic nuances that have broad implications for the workup of ICH and the
      strategic management of a unique scenario involving a brain AVM and high-grade
      cranial dural fistula in the same patient. Prior to each procedure, informed
      consent was obtained from the patient, which includes consent for publication.

PMID- 30202997
TI  - Commentary on: Evaluation of Retropectoral Fat Grafting in Breast Reduction by
      Magnetic Resonance Imaging: A Pilot Study.

PMID- 30202996
TI  - Reassessing the Global Mortality Burden of the 1918 Influenza Pandemic.
AB  - Mortality estimates of the 1918 influenza pandemic vary considerably, and recent
      estimates have suggested that there were 50 million to 100 million deaths
      worldwide. We investigated the global mortality burden using an indirect
      estimation approach and 2 publicly available data sets: the Human Mortality
      Database (13 countries) and data extracted from the records of the Statistical
      Abstract for British India. The all-cause Human Mortality Database was used to
      estimate mortality annually for 1916-1921 for detailed age groups. Three
      different calculation methods were applied to the data (low, medium, and high
      scenarios), and we used a multilevel regression model to control for distorting
      factors (e.g., war and the underlying time trend in mortality). Total pandemic
      mortality was an estimated 15 million deaths worldwide in 1918 (n = 2.5 million
      in 1919) after including the rates for British India and controlling for wars and
      the underlying mortality trend. According to our validity analysis, simulations
      of total number of deaths being greater than 25 million are not realistic based
      on the underlying mortality rates included in Human Mortality Database and in
      British India. Our results suggest the global death impact of the 1918 pandemic
      was important (n = 17.4 million) but not as severe as most frequently cited
      estimates.

PMID- 30202998
TI  - Hormonal and Metabolic Effects of Coenzyme Q10 and/or Vitamin E in Patients with
      Polycystic Ovary Syndrome.
AB  - Context: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder
      in reproductive age women. No study has examined the hormonal and metabolic
      effects of coenzyme Q10 and/or vitamin E in patients with PCOS. Objective: To
      evaluate the effects of coenzyme Q10 and/or vitamin E on glucose homeostasis
      parameters and reproductive hormones in women with PCOS.
      Design/Setting/Participants: Randomized double-blind placebo-controlled clinical
      trial among 86 women with PCOS. Intervention: Coenzyme Q10 (CoQ10) or vitamin E
      or combination for 8 weeks. Main Outcome Measures: Glucose homeostasis parameters
      and sex hormones concentrations. Results: We observed that, after adjustment for
      potential confounders, supplementation with CoQ10 alone or in combination with
      vitamin E, compared with placebo, had significant effects on fasting blood sugar
      (FBS), while the effect of vitamin E on FBS was not statistically significant. A
      significant reduction in homeostasis model assessment of insulin resistance (HOMA
      IR) was observed in the CoQ10 and combined groups. CoQ10, vitamin E and Co
      supplementation compared with the placebo group, led to decreased serum total
      testosterone levels (P<0.001). CoQ10 supplementation in combination with vitamin
      E resulted in a significant improvement in sex hormone-binding globulin (SHBG)
      compared to other groups (P=0.008). Findings from linear regression analysis
      revealed that changes in FBS, insulin, and HOMA-IR were predictors of change in
      FAI (P<0.05). Conclusions: In conclusion, CoQ10 with or without vitamin E
      supplementation among women with PCOS had beneficial effects on serum FBS and
      insulin levels as well as HOMA-IR and total testosterone levels. However only co
      supplementation was able to affect SHBG concentrations.

PMID- 30202999
TI  - CATANA: a tool for generating comprehensive annotations of alternative transcript
      events.
AB  - Summary: In higher eukaryotes, the generation of transcript isoforms from a
      single gene through alternative splicing (AS) and alternative transcription (AT)
      mechanisms increases functional and regulatory diversities. Annotating these
      alternative transcript events is essential for genomic studies. However, there
      are no existing tools that generate comprehensive annotations of all these
      alternative transcript events including both AS and AT events. In the present
      study, we develop CATANA, with the encoded exon usage patterns based on the
      flattened gene model, to identify ten types of AS and AT events. We demonstrate
      the power and versatility of CATANA by showing greater depth of annotations of
      alternative transcript events according to either genome annotation or RNA-seq
      data. Availability and Implementation: CATANA is available on
      https://github.com/shiauck/CATANA. Supplementary information: Supplementary data
      are available at Bioinformatics online.

PMID- 30203000
TI  - Experimental evidence for an inhibitory role of AhR activation in human
      mesenchymal stem cell differentiation.
AB  - Multipotent mesenchymal stem cells maintain the ability to differentiate into
      adipogenic, chondrogenic, or osteogenic cell lineages. There is increasing
      concern that exposure to environmental agents such as aryl hydrocarbon receptor
      (AhR) ligands, may perturb the osteogenic pathways responsible for normal bone
      formation. The objective of the current study was to evaluate the potential of
      the prototypic AhR ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to disrupt
      osteogenic differentiation of human bone-derived mesenchymal stem cells (hBMSCs)
      in vitro. Primary hBMSCs from three donors were exposed to 10 nM TCDD and
      differentiation was interrogated using select histological, biochemical, and
      transcriptional markers of osteogenesis. Exposure to 10 nM TCDD resulted in an
      overall consistent attenuation of alkaline phosphatase (ALP) activity and matrix
      mineralization at terminal stages of differentiation in primary hBMSCs. At the
      transcriptional level, the transcriptional regulator DLX5 and additional
      osteogenic markers (ALP, OPN, and IBSP) displayed attenuated expression;
      conversely, FGF9 and FGF18 were consistently upregulated in each donor.
      Expression of stem cell potency markers SOX2, NANOG, and SALL4 decreased in the
      osteogenic controls, while expression in TCDD-treated cells resembled that of
      undifferentiated cells. Co-exposure with the AhR antagonist GNF351 blocked TCDD
      mediated attenuation of matrix mineralization, and either fully or partially
      rescued expression of genes associated with osteogenic regulation, ECM, and/or
      maintenance of multipotency. Thus, experimental evidence from this study suggests
      that AhR transactivation likely attenuates osteoblast differentiation in
      multipotent hBMSCs. This study also underscores the use of primary human MSCs to
      evaluate osteoinductive or osteotoxic potential of chemical and pharmacologic
      agents in vitro.

PMID- 30203001
TI  - $?ell_1$-Penalized censored Gaussian graphical model.
AB  - Graphical lasso is one of the most used estimators for inferring genetic
      networks. Despite its diffusion, there are several fields in applied research
      where the limits of detection of modern measurement technologies make the use of
      this estimator theoretically unfounded, even when the assumption of a
      multivariate Gaussian distribution is satisfied. Typical examples are data
      generated by polymerase chain reactions and flow cytometer. The combination of
      censoring and high-dimensionality make inference of the underlying genetic
      networks from these data very challenging. In this article, we propose an
      $?ell_1$-penalized Gaussian graphical model for censored data and derive two EM
      like algorithms for inference. We evaluate the computational efficiency of the
      proposed algorithms by an extensive simulation study and show that, when censored
      data are available, our proposal is superior to existing competitors both in
      terms of network recovery and parameter estimation. We apply the proposed method
      to gene expression data generated by microfluidic Reverse Transcription
      quantitative Polymerase Chain Reaction technology in order to make inference on
      the regulatory mechanisms of blood development. A software implementation of our
      method is available on github (https://github.com/LuigiAugugliaro/cglasso).

PMID- 30203003
TI  - Conditional Approximate Bayesian Computation: A New Approach for Across-Site
      Dependency in High-Dimensional Mutation-Selection Models.
AB  - A key question in molecular evolutionary biology concerns the relative roles of
      mutation and selection in shaping genomic data. Moreover, features of mutation
      and selection are heterogeneous along the genome and over time. Mechanistic codon
      substitution models based on the mutation-selection framework are promising
      approaches to separating these effects. In practice, however, several
      complications arise, since accounting for such heterogeneities often implies
      handling models of high dimensionality (e.g., amino acid preferences), or leads
      to across-site dependence (e.g., CpG hypermutability), making the likelihood
      function intractable. Approximate Bayesian Computation (ABC) could address this
      latter issue. Here, we propose a new approach, named Conditional ABC (CABC),
      which combines the sampling efficiency of MCMC and the flexibility of ABC. To
      illustrate the potential of the CABC approach, we apply it to the study of
      mammalian CpG hypermutability based on a new mutation-level parameter implying
      dependence across adjacent sites, combined with site-specific purifying selection
      on amino-acids captured by a Dirichlet process. Our proof-of-concept of the CABC
      methodology opens new modeling perspectives. Our application of the method
      reveals a high level of heterogeneity of CpG hypermutability across loci and mild
      heterogeneity across taxonomic groups; and finally, we show that CpG
      hypermutability is an important evolutionary factor in rendering relative
      synonymous codon usage. All source code is available as a GitHub repository
      (https://github.com/Simonll/LikelihoodFreePhylogenetics.git).

PMID- 30203002
TI  - Congenital rubella syndrome surveillance in South Africa using a sentinel site
      approach: a cross-sectional study.
AB  - Background: Congenital rubella syndrome (CRS) includes disorders associated with
      intrauterine rubella infection. Incidence of CRS is higher in countries with no
      rubella-containing vaccines (RCV) in their immunization schedules. In the World
      Health Organization African region, RCVs are being introduced as part of the 2012
      2020 global measles and rubella strategic plan. This study aimed to describe the
      epidemiology of confirmed CRS in South Africa prior to introduction of RCVs in
      the immunization schedule. Methods: This was a descriptive study with 28 sentinel
      sites reporting laboratory-confirmed CRS cases in all nine provinces of South
      Africa. In the retrospective phase (2010 to 2014), CRS cases were retrieved from
      medical records and in the prospective phase (2015 to 2017) clinicians at study
      sites reported CRS cases monthly. Results: There were 42 confirmed CRS cases in
      the retrospective phase and 53 confirmed CRS cases in the prospective phase. Most
      frequently reported birth defects were congenital heart disease and cataracts.
      The median age of mothers of CRS cases was 21 years in the retrospective phase
      (range: 11 to 38 years) and 22 years in the prospective phase (range: 15 to 38
      years). Conclusion: Baseline data on laboratory-confirmed CRS will enable
      planning and monitoring of RCV implementation in the South African EPI program.
      Ninety-eight percent of mothers of infants with CRS were young women 14 to 30
      years old, indicating a potential immunity gap in this age group for
      consideration during introduction of RCV.

PMID- 30203005
TI  - Incidence of Arthritis/Arthralgia in Inflammatory Bowel Disease with Long-term
      Vedolizumab Treatment: Post Hoc Analyses of the GEMINI Trials.
AB  - Background and Aims: Extraintestinal manifestations (EIMs) such as
      arthritis/arthralgia are common in inflammatory bowel disease. We performed post
      hoc analyses of data from the GEMINI studies to evaluate the effect of
      vedolizumab, a gut-selective anti-trafficking agent, on arthritis/arthralgia.
      Methods: Sustained resolution of baseline arthritis/arthralgia, worsening of
      baseline arthritis/arthralgia, the occurrence of new arthritis/arthralgia, and
      the composite of new/worsening arthritis/arthralgia were evaluated. Cox modelling
      was used for time-to-event analysis. Influence of corticosteroid-tapering was
      also investigated. Results: In Crohn's disease (CD) patients, vedolizumab was
      significantly less likely than placebo to be associated with new/worsening
      arthritis/arthralgia (hazard ratio [HR], 0.63; 95% CI, 0.44-0.89). Similar
      incidences of sustained resolution of arthritis/arthralgia occurred with
      vedolizumab and placebo. In CD patients on corticosteroids at baseline,
      corticosteroid dose-decrease increased the risk of new/worsening
      arthritis/arthralgia (odds ratio [OR], 7.49; 95% CI, 3.50-15.97) regardless of
      treatment; and in those achieving corticosteroid-free status,
      arthritis/arthralgia was less likely with vedolizumab than placebo (HR, 0.14; 95%
      CI, 0.05-0.35). In ulcerative colitis (UC) patients, vedolizumab and placebo
      showed similar incidence of new/worsening of arthritis/arthralgia. In UC patients
      on corticosteroid at baseline, arthritis/arthralgia was more likely in those
      achieving corticosteroid-free status than in those continuing corticosteroids (HR
      2.63 [95% CI 1.13-6.11]); and in those achieving corticosteroid-free status,
      incidence of arthritis/arthralgia was similar with vedolizumab and placebo.
      Conclusions: Vedolizumab therapy was associated with a reduced likelihood of
      new/worsening arthritis/arthralgia in CD and no increased incidence of these
      events in UC. Studies included (ClincialTrials.gov, number): GEMINI 1
      (NCT00783718); GEMINI 2 (NCT00783692); GEMINI 3 (NCT01224171).

PMID- 30203004
TI  - Mechanism of Telapristone Acetate (CDB4124) on Progesterone Receptor Action in
      Breast Cancer Cells.
AB  - Progesterone is a steroid hormone that plays an important role in the breast.
      Progesterone exerts its action through binding to progesterone receptor (PR), a
      transcription factor. Deregulation of the progesterone signaling pathway is
      implicated in the formation, development, and progression of breast cancer. Next
      generation selective progesterone receptor modulators (SPRMs) have potent
      antiprogestin activity and are selective for PR, reducing the off-target effects
      on other nuclear receptors. To date, there is limited information on how the
      newer generation of SPRMs, specifically telapristone acetate (TPA), affect PR
      function at the molecular level. In this study, T47D breast cancer cells were
      used to investigate the molecular mechanism by which TPA antagonizes PR action.
      Global profiling of the PR cistrome and interactome was done with chromatin
      immunoprecipitation sequencing (ChIP-seq) and rapid immunoprecipitation mass
      spectrometry. Validation studies were done on key genes and interactions. Our
      results demonstrate that treatment with the progestin (R5020) alone resulted in
      robust PR recruitment to the chromatin, and addition of TPA reduced PR
      recruitment globally. TPA significantly changed coregulator recruitment to PR
      compared with R5020. Upon conservative analysis, three proteins (TRPS1, LASP1,
      and AP1G1) were identified in the R5020+TPA-treated group. Silencing TRPS1 with
      small interfering RNA increased PR occupancy to the known PR regulatory regions
      and attenuated the inhibition of gene expression after TPA treatment. TRPS1
      silencing alleviated the inhibition of proliferation by TPA. In conclusion, TPA
      decreases PR occupancy on chromatin and recruits coregulators such as TRPS1 to
      the PR complex, thereby regulating PR target gene expression and associated
      cellular responses.

PMID- 30203007
TI  - Multimodal Treatment Options, Including Rotating to Buprenorphine, Within a
      Multidisciplinary Pain Clinic for Patients on Risky Opioid Regimens: A Quality
      Improvement Study.
AB  - Objectives: We aimed to evaluate a novel clinical program designed to address
      unsafe use of opioids prescribed for pain-the Opioid Reassessment Clinic (ORC)-to
      inform practice and health system improvement. Design: Controlled, retrospective
      cohort study. Setting: The ORC is a multidisciplinary clinic in a primary care
      setting in a Veterans Health Administration hospital designed to perform
      longitudinal treatment of patients with unsafe use of opioids prescribed for
      pain, including tapering or rotating to the partial opioid agonist buprenorphine.
      Subjects: We included patients referred to the ORC from March 1, 2016, to March
      1, 2017, who had an intake appointment (intervention group) and who did not
      (control group). Methods: We compared a priori-defined metrics at the patient,
      clinic process, and health system levels and compared metrics between groups.
      Results: During the study period, 114 veterans were referred to the ORC, and 71
      (62%) of these had an intake appointment. Those in the intervention group were
      more likely to trial buprenorphine (N = 41, 62% vs N = 1, 2%, P < 0.01) and had
      greater reductions in their full agonist morphine equivalent daily dose than
      those in the control group (30 mg [interquartile range {IQR} = 0-120] vs 0 mg
      [IQR = 0-20] decrease, P < 0.01). Of those engaging in the ORC, 20 (30%) had not
      transitioned chronic pain management back to their primary care providers (PCPs)
      by the end of follow-up. Only one patient transitioned the management of
      buprenorphine to the PCP. Conclusions: Results suggest the ORC was effective in
      reducing total prescribed opioid doses and in transitioning patients to partial
      agonist therapy, but PCP adoption strategies are needed.

PMID- 30203006
TI  - Impact of lesion complexity on peri-procedural adverse events and the benefit of
      potent intravenous platelet adenosine diphosphate receptor inhibition after
      percutaneous coronary intervention: core laboratory analysis from 10 854 patients
      from the CHAMPION PHOENIX trial.
AB  - Aims: In the CHAMPION PHOENIX trial, the potent, rapidly acting, intravenous
      platelet adenosine diphosphate receptor antagonist cangrelor reduced the 48-h
      incidence of major adverse cardiac events (MACE; death, myocardial infarction,
      stent thrombosis, or ischaemia-driven revascularization) compared with a loading
      dose of clopidogrel in patients undergoing percutaneous coronary intervention
      (PCI). We sought to determine whether the efficacy of cangrelor during PCI varies
      in patients with simple vs. complex target lesion coronary anatomy. Methods and
      results: Blinded angiographic core laboratory analysis was completed in 10 854 of
      10 942 (99.2%) randomized patients in CHAMPION PHOENIX (13 418 target lesions).
      Outcomes were analysed according to the number of angiographic PCI target lesion
      high-risk features (HRF) present (bifurcation, left main, thrombus, angulated,
      tortuous, eccentric, calcified, long, or multi-lesion treatment). The number of
      patients with 0, 1, 2, and >=3 HRFs was 1817 (16.7%), 3442 (31.7%), 2901 (26.7%),
      and 2694 (24.8%), respectively. The 48-h MACE rate in clopidogrel-treated
      patients increased progressively with lesion complexity (from 3.3% to 4.4% to
      6.9% to 8.7%, respectively, P < 0.0001). Cangrelor reduced the 48-h rate of MACE
      by 21% {4.7% vs. 5.9%, odds ratio (OR) [95% confidence interval (95% CI)] 0.79
      (0.67, 0.93), P = 0.006} compared with clopidogrel, an effect which was
      consistent regardless of PCI lesion complexity (Pinteraction = 0.66) and
      presentation with stable ischaemic heart disease (SIHD) or an acute coronary
      syndrome (ACS). By multivariable analysis, the number of high-risk PCI
      characteristics [OR (95% CI) 1.68 (1.20, 2.36), 2.78 (2.00, 3.87), and 3.23
      (2.33, 4.48) for 1, 2, and 3 HRFs compared with 0 HRFs, all P < 0.0001] and
      treatment with cangrelor vs. clopidogrel [OR (95% CI) 0.78 (0.66, 0.92), P =
      0.004] were independent predictors of the primary 48-h MACE endpoint. Major
      bleeding rates were unrelated to lesion complexity and were not increased by
      cangrelor. Conclusion: Peri-procedural MACE after PCI is strongly dependent on
      the number of treated high-risk target lesion features. Compared with a loading
      dose of clopidogrel, cangrelor reduced MACE occurring within 48 h after PCI in
      patients with SIHD and ACS regardless of baseline lesion complexity. The absolute
      benefit:risk profile for cangrelor will therefore be greatest during PCI in
      patients with complex coronary anatomy. Clinicaltrials.gov identifier:
      NCT01156571.

PMID- 30203008
TI  - The Association of Obstructive Sleep Apnea and Pain Outcomes in Adults: A
      Systematic Review.
AB  - Objective: The specific link between obstructive sleep apnea (OSA) and pain is
      unknown, but it has been hypothesized that OSA patients are hyperalgesic because
      of fragmented sleep and hypoxemia that enhance sensitivity to pain, promote
      inflammation, and increase spontaneous pain. We conducted a systematic review of
      the literature assessing whether OSA is a risk factor for subjective pain
      intensity and experimental pain tolerance and threshold. Design/Participants: A
      search of published studies in English in MEDLINE, PubMed, Embase, and the
      Cochrane Database of Systematic Reviews from database inception through May 2017
      was performed. Search terms included "sleep apnea," "continuous positive airway
      pressure," "CPAP," "pain," and "chronic pain." Methods: We included any study
      that reported an association between OSA or polysomnogram assessments with pain
      outcomes or reported the effect of CPAP on pain outcomes. Controlled studies,
      cohort studies, and case-control studies were included. Results: We identified
      448 studies from PubMed and 959 studies from Embase, giving a combined 1,333
      studies after removing duplicates. After detailed selection, 28 articles were
      reviewed in full and 12 met study inclusion criteria. Whereas several studies
      found an association between OSA and pain intensity or experimental pain, there
      was considerable variability among study outcomes. Delivery of CPAP may improve
      pain and decrease opioid use, although the exact nature of the relationship
      between pain and the various pathophysiologic components of OSA is unclear.
      Conclusions: This systematic review summarizes the current evidence for the
      association of OSA and pain outcomes. Further research is needed to identify the
      differential effects of nocturnal hypoxemia and fragmented sleep on pain
      intensity. Clinicians might consider screening patients with chronic pain for
      OSA.

PMID- 30203009
TI  - Patient Experiences Navigating Chronic Pain Management in an Integrated Health
      Care System: A Qualitative Investigation of Women and Men.
AB  - Background: Rates of pain among veterans are as high as 60%; rates approach 80%
      in women seeking Department of Veterans Affairs (VA) care. Prior studies examined
      experiences managing pain in community samples, with gender disparities observed.
      As the largest national integrated health care system in the country, the VA
      offers a unique environment to a) study perceptions of pain care among men and
      women and b) contrast experiences using an integrated health care setting with
      prior observations in the private sector. Methods: A purposive sample of chronic
      pain patients was recruited to qualitatively describe perceptions of managing
      pain in an integrated health care system (VA) and to explore gender differences.
      A constant comparative approach with sequential analysis was used to reach
      thematic consensus. Results: Ten focus groups (N = 48; six groups of women [N =
      22]; four groups of men [N = 26]) revealed an overarching theme, "just keep
      plugging," which reflected pain as a constant struggle. Three subthemes emerged:
      "always a reacquaintance process" described frustration with the use of trainees
      in the medical center. The need to navigate "so many hoops" referred to
      frustrations with logistical barriers. "To medicate or not" reflected tensions
      around medication use. A distinct theme, "the challenges of being female,"
      reflected women's perceptions of stigma and bias. Conclusions: Most of the
      identified challenges were not unique to the integrated setting. Findings
      revealed advantages to receiving pain care in this setting. Tensions between
      patient expectations and guidelines governing provider behavior emerged. Improved
      patient education, provider communication and sensitivity to the unique needs of
      women may optimize care.

PMID- 30203010
TI  - Academic Detailing to Improve Opioid Safety: Implementation Lessons from a
      Qualitative Evaluation.
AB  - Objective: Academic detailing (AD) is a promising intervention to address the
      growing morbidity and mortality associated with opioids. While AD has been shown
      to be effective in improving provider prescribing practices across a range of
      conditions, it is unclear how best to implement AD. The present study was
      designed to identify key lessons for implementation based on a model AD program
      in the Veterans Health Administration (VA). Design: Qualitative process
      evaluation using semistructured interviews. Setting: Seven VA health care systems
      in the Sierra Pacific region. Subjects: Current and former academic detailers (N
      = 10) and VA providers with varying exposure to AD (high, low, or no; N = 20).
      Methods: Semistructured interviews were audio-recorded and transcribed. We used a
      team-based, mixed inductive and deductive approach guided by the Consolidated
      Framework for Implementation Research. Results: Key lessons identified by
      academic detailers and providers coalesced around key themes: 1) one-on-one
      sessions customized to the provider's patient population are most useful; 2)
      leadership plays a critical role in supporting providers' participation in AD
      programs; 3) tracking academic detailer and provider performance is important for
      improving performance for both groups; 4) academic detailers play a key role in
      motivating provider behavior change and thus training in Motivational
      Interviewing is highly valuable; and 5) academic detailers noted that networking
      is important for sharing implementation strategies and resources. Conclusions:
      Identifying and incorporating these key lessons into the implementation of
      complex interventions like AD are critical to facilitating uptake of evidence
      based interventions addressing the opioid epidemic.

PMID- 30203011
TI  - A Brief, Integrated, Telephone-Based Intervention for Veterans Who Smoke and Have
      Chronic Pain: A Feasibility Study.
AB  - Objective: High rates of co-occurring smoking and chronic pain are observed in
      the veteran population. Individuals who smoke and have chronic pain report lower
      self-efficacy to quit and are less successful in their attempts. Design: In this
      pilot study, we assess the feasibility of a telephone-delivered intervention
      designed to integrate evidence-based smoking cessation and pain management
      components in a way that allows patients to understand the interplay between the
      two while attempting to have them build off each other and develop coping skills
      to address both concerns. Patients: Study participants (N = 7) were veterans who
      received primary care in the VA Healthcare System and reported current smoking
      and a worst pain intensity score of 4 or greater. Intervention: A five-session
      telephone intervention was delivered over eight weeks. Participants completed a
      survey at baseline and 10-week follow-up. Outcome Measures: Feasibility was
      assessed by examining engagement with the intervention. Results: Four out of
      seven participants completed all five sessions. Two out of seven veterans
      reported quitting smoking, and five out of seven reported clinically meaningful
      improvements in pain intensity and functional interference. Conclusions: Insights
      gained from this study were used to modify an intervention being examined in a
      randomized controlled trial to test its effectiveness on both smoking and pain
      outcomes.

PMID- 30203012
TI  - Understanding Pain and Pain Treatment for Veterans: Responding to the Federal
      Pain Research Strategy.

PMID- 30203013
TI  - Variation in National Opioid Prescribing Patterns Following Surgery for Kidney
      Stones.
AB  - Background: Opioid misuse is a significant public health problem. As initial
      exposures to opioids are frequently encountered through the management of
      postoperative pain, we examined patterns of opioid prescribing following surgical
      treatment for nephrolithiasis. Methods: We identified patients with
      nephrolithiasis in the national Women Veterans Cohort Study (WVCS) who were
      treated surgically by diagnosis and procedure codes. Using standard conversion
      factors, we calculated the morphine milligram equivalent (MME) dose prescribed.
      We used descriptive statistics to characterize opioid prescription across
      management strategy and multivariable regression to examine clinical and
      demographic characteristics associated with dispensed dose. Results: We
      identified 22,609 patients diagnosed with kidney stones during 1999-2014, 1,976
      of whom were treated surgically and 1,582 (80.1%) of whom received an opioid
      prescription. The median age was 39 years, and 1,366 (90%) were male; 1,314
      (86.3%) were treated with ureteroscopy, 172 (11.3%) with extracorporeal shockwave
      lithotripsy, and 36 (2.4%) with percutaneous nephrolithotomy. The median number
      of days supplied per opioid prescription (interquartile range) was 10 (5-14), and
      patients were dispensed a median of 180 (140-300) MME. A total of 6.4% of
      patients received >=50 MME/d. On multivariable analysis, comorbid diagnosis of
      post-traumatic stress disorder (PTSD) was associated with higher total dispensed
      dose, whereas surgery type was not. Conclusions: We observed substantial
      variation in opioid prescribing following surgical treatment of nephrolithiasis.
      Although type of surgical intervention did not impact opioid dosing, patients
      with a diagnosis of PTSD were more likely to receive higher doses. This work can
      inform efforts to improve the safety and efficacy of postoperative opioid
      prescribing.

PMID- 30203014
TI  - Opioid Use Among Veterans of Recent Wars Receiving Veterans Affairs Chiropractic
      Care.
AB  - Objective: To examine patient sociodemographic and clinical characteristics
      associated with opioid use among Veterans of Operations Enduring Freedom/Iraqi
      Freedom/New Dawn (OEF/OIF/OND) who receive chiropractic care, and to explore the
      relationship between timing of a chiropractic visit and receipt of an opioid
      prescription. Methods: Cross-sectional analysis of administrative data on
      OEF/OIF/OND veterans who had at least one visit to a Veterans Affairs (VA)
      chiropractic clinic between 2004 and 2014. Opioid receipt was defined as at least
      one prescription within a window of 90 days before to 90 days after the index
      chiropractic clinic visit. Results: We identified 14,025 OEF/OIF/OND veterans
      with at least one chiropractic visit, and 4,396 (31.3%) of them also received one
      or more opioid prescriptions. Moderate/severe pain (odds ratio [OR] = 1.87, 95%
      confidence interval [CI] = 1.72-2.03), PTSD (OR = 1.55, 95% CI = 1.41-1.69),
      depression (OR = 1.40, 95% CI = 1.29-1.53), and current smoking (OR = 1.39, 95%
      CI = 1.26-1.52) were associated with a higher likelihood of receiving an opioid
      prescription. The percentage of veterans receiving opioid prescriptions was lower
      in each of the three 30-day time frames assessed after the index chiropractic
      visit than before. Conclusions: Nearly one-third of OEF/OIF/OND veterans
      receiving VA chiropractic services also received an opioid prescription, yet the
      frequency of opioid prescriptions was lower after the index chiropractic visit
      than before. Further study is warranted to assess the relationship between opioid
      use and chiropractic care.

PMID- 30203015
TI  - Project STEP: Implementing the Veterans Health Administration's Stepped Care
      Model of Pain Management.
AB  - Objective: The "stepped care model of pain management" (SCM-PM) prioritizes the
      role of primary care providers in optimizing pharmacological management and
      timely and equitable access to patient-centered, evidence-based
      nonpharmacological approaches, when indicated. Over the past several years, the
      Veterans Health Administration (VHA) has supported implementation of SCM-PM, but
      few data exist regarding changes in pain care resulting from implementation. We
      examined trends in prescribing and referral practices of primary care providers
      with hypotheses of decreased opioid prescribing, increased nonopioid prescribing,
      and increased referrals to specialty care for nonpharmacological services.
      Design: An initiative was designed to foster implementation and systematic
      evaluation of the SCM-PM over a five-year period at the VA Connecticut Healthcare
      System (VACHS) while fostering collaborative, partnered initiatives to promote
      organizational improvements in the delivery of pain care. Subjects: Participants
      were veterans receiving care at VACHS with at least one pain intensity rating
      >=4/10 over the course of the study period (7/2008-6/2013). Methods: We used
      electronic health record data to examine changes in indicators of pain care
      including pharmacy and health care utilization data. Results: We observed
      hypothesized changes in long-term opioid and nonopioid analgesic prescribing and
      increased utilization of nonpharmacological treatments such as physical therapy,
      occupational therapy, and clinical health psychology. Conclusions: Through a
      multifaceted comprehensive implementation approach, primary care providers
      demonstrated increases in guideline-concordant pain care practices. Findings
      suggest that engagement of interdisciplinary teams and partnerships to promote
      organizational improvements is a useful strategy to increase the use of
      integrated, multimodal pain care for veterans, consistent with VHA's SCM-PM.

PMID- 30203016
TI  - Relationships Between Temporomandibular Disorders, MSD Conditions, and Mental
      Health Comorbidities: Findings from the Veterans Musculoskeletal Disorders
      Cohort.
AB  - Objective: Temporomandibular disorders (TMDs) have been associated with other
      chronic painful conditions (e.g., fibromyalgia, headache) and suicide and mood
      disorders. Here we examined musculoskeletal, painful, and mental health
      comorbidities in men vs women veterans with TMD (compared with non-TMD
      musculoskeletal disorders [MSDs] cases), as well as comorbidity patterns within
      TMD cases. Design: Observational cohort. Setting: National Veterans Health
      Administration. Subjects: A cohort of 4.1 million veterans having 1+ MSDs,
      entering the cohort between 2001 and 2011. Methods: Chi-square tests, t tests,
      and logistic regression were utilized for cross-sectional analysis. Results:
      Among veterans with any MSD, those with TMD were younger and more likely to be
      women. The association of TMD with race/ethnicity differed by sex. Odds of TMD
      were higher in men of Hispanic ethnicity (OR = 1.38, 95% CI = 1.27-1.48) and
      nonwhite race/ethnicity other than black or Hispanic (OR = 1.29, 95% CI = 1.16
      1.45) compared with white men. Odds of TMD were significantly lower for black (OR
      = 0.54, 95% CI = 0.49-0.60) and Hispanic women (OR = 0.84, 95% CI = 0.73-0.995)
      relative to white women. Non-MSD comorbidities (e.g., irritable bowel syndrome,
      mental health, headaches) were significantly associated with TMD in male
      veterans; their pattern was similar in women. Veterans with back pain,
      nontraumatic joint disorder, or osteoarthritis had more MSD multimorbidity than
      those with TMD. Conclusions: Complex patterns of comorbidity in TMD cases may
      indicate different underlying mechanisms of association in subgroups or
      phenotypes, thereby suggesting multiple targets to improve TMD. Longitudinal
      comprehensive studies powered to look at sex and racial/ethnic groupings are
      needed to identify targets to personalize care.

PMID- 30203017
TI  - Impact of Cigarette Smoking Status on Pain Intensity Among Veterans With and
      Without Hepatitis C.
AB  - Objective: Chronic pain is a significant problem in patients living with
      hepatitis C virus (HCV). Tobacco smoking is an independent risk factor for high
      pain intensity among veterans. This study aims to examine the independent
      associations with smoking and HCV on pain intensity, as well as the interaction
      of smoking and HCV on the association with pain intensity. Design/Particpants:
      Cross-sectional analysis of a cohort study of veterans of Operations Enduring
      Freedom/Iraqi Freedom/New Dawn (OEF/OIF/OND) who had at least one visit to a
      Veterans Health Administration (VHA) primary care clinic between 2001 and 2014.
      Methods: HCV was identified using ICD-9 codes from electronic medical records
      (EMRs). Pain intensity, reported on a 0-10 numeric rating scale, was categorized
      as none/mild (0-3) and moderate/severe (4-10). Results: Among 654,841 OEF/OIF/OND
      veterans (median age [interquartile range] = 26 [23-36] years), 2,942 (0.4%) were
      diagnosed with HCV. Overall, moderate/severe pain intensity was reported in 36%
      of veterans, and 37% were current smokers. The adjusted odds of reporting
      moderate/severe pain intensity were 1.23 times higher (95% confidence interval
      [CI] = 1.14-1.33) for those with HCV and 1.26 times higher (95% CI = 1.25-1.28)
      for current smokers. In the interaction model, there was a significant Smoking
      Status * HCV interaction (P = 0.03). Among veterans with HCV, smoking had a
      significantly larger association with moderate/severe pain (adjusted odds ratio
      [OR] = 1.50, P < 0.001) than among veterans without HCV (adjusted OR = 1.26, P <
      0.001). Conclusions: We found that current smoking is more strongly linked to
      pain intensity among veterans with HCV. Further investigations are needed to
      explore the impact of smoking status on pain and to promote smoking cessation and
      pain management in veterans with HCV.

PMID- 30203018
TI  - Distribution of dipeptidyl peptidase (DPP) 4, DPP5, DPP7 and DPP11 in human oral
      microbiota-potent biomarkers indicating presence of periodontopathic bacteria.
AB  - Dipeptidyl peptidase (DPP) 4, DPP5, DPP7 and DPP11, expressed in the periplasmic
      space, are crucial for energy production for Porphyromonas gingivalis, an
      asaccharolytic bacterium that causes periodontal disease. Bacterial DPP4 seems to
      be involved in regulation of blood glucose level via degradation of incretins.
      The present study aimed to identify four dpp orthologs in oral microbiota by
      database searches, and their enzymatic activities in periodontopathic and
      cariogenic bacteria, as well as oral specimens were determined. Search in the
      databases suggested that 43 species of 772 taxa possess dpp4 and other dpp genes.
      Most species are in the genera Bacteroides, Capnocytophaga, Porphyromonas,
      Prevotella and Tannerella, indicating a limited distribution of dpp orthologs in
      anaerobic periodontopathic rods. In accordance with those results, activities of
      all four DPPs were demonstrated in P. gingivalis, Porphyromonas endodontalis and
      Tannerella forsythia, while they were negligible in Treponema denticola,
      Fusobacterium nucleatum and Aggregatibacter actinomycetemcomitans. Furthermore,
      DPP activities were also detected in subgingival dental plaque at different
      intensities among individual specimens, while DPP4 activity presumably derived
      from human entity was solely predominant in saliva samples. These findings
      demonstrated that DPP activities in dental plaque serve as potent biomarkers to
      indicate the presence of periodontopathic bacteria.

PMID- 30203019
TI  - In Reply: Increased Body Mass Index Associated With Reduced Risk of Delayed
      Cerebral Ischemia and Subsequent Infarction After Aneurysmal Subarachnoid
      Hemorrhage.

PMID- 30203020
TI  - How to reduce biases coming from a before and after design: the impact of the
      2007-08 French smoking ban policy.
AB  - Background: Smoke-free laws aim at protecting against second-hand smoke and at
      contributing to change smoking behaviors. Impact evaluation studies can help
      understand to what extent they reach their goals. Simple before and after designs
      are often used but cannot isolate the effect of the policy of interest. Methods:
      The short-term impact of the French smoking ban (2007-08) on smoking behavior
      outcomes was evaluated among smokers with data from the ITC project. We first
      conducted a before and after design on the French sample. Second, we added the UK
      (excluding Scotland) as a control group and finally used external pre-policy data
      from national surveys to control for bias arising from pre-policy trends.
      Results: After one year post-implementation, the smoking ban led to a decrease in
      seeing people smoking in bars, restaurants and workplaces [estimated risk ratios
      (RR) of 8.81 IC95% (5.34-14.71), 2.02 (1.79-2.31) and 1.24 (1.16-1.33),
      respectively], as well as an increase in support for the smoke-free policy, but
      only in bars and restaurants [RR of 1.35 (1.15-1.61) and 1.25 (1.16-1.35)],
      respectively. No impact was found on smoking behaviors and on having a strict no
      smoking policy at home. The simple before and after design systematically
      overestimated the smoking ban's impact [e.g. RR of 29.9 (20.06-44.56) for
      observed smoking in bar, compared to 13.21 (7.78-22.42) with the control group,
      and 8.81 (5.34-14.71) with the correction from external data]. Conclusion: When
      data are lacking to conduct quasi-experimental designs for impact evaluation, the
      use of external data could help understand and correct pre-policy trends.

PMID- 30203021
TI  - Precursors of delayed sleep phase in adolescence: a population-based longitudinal
      study.
AB  - Study Objective: The aim of this study was to assess sleep behavior, sleep
      problems and mental health in childhood as possible candidate precursors for the
      development of delayed sleep phase (DSP) during adolescence. Methods: A
      longitudinal cohort study of 2200 children at age 7-9 (T1), 11-13 (T2), and 16-19
      (T3) years. DSP was assessed at T3, and mental health problems by the Strength
      and Difficulties Questionnaire and time in bed and sleep problems at T1 and T2.
      Logistic regression analyses were used to examine associations between sleep and
      mental health at T1 and T2, and subsequent DSP at T3. Estimated marginal means
      were computed to compare mental health at T1 and T2 in adolescents with and
      without DSP. Results: Sleeping less than 9 hours per night at age 11-13 was
      significantly associated with DSP at 16-19 years (adjusted odds ratio = 3.37).
      Sleep problems at 11-13 years of age were more frequent among those who developed
      DSP compared to children who did not develop DSP (20% vs. 12%) but the results
      did not remain significant when controlling for early mental health problems.
      Sleep problems and mental health at 7-9 years of age was not related to later
      DSP. In the crude analyses, all Strengths and Difficulties Questionnaire (SDQ)
      subscales at 11-13 years was significantly associated with later DSP, but in the
      fully adjusted analysis, only the SDQ total score and hyperactivity subscale
      remained statistically significant. Conclusion: Children with DSP in adolescence
      possess identifiable risk indicators in childhood.

PMID- 30203022
TI  - The GCTx format and cmap{Py, R, M, J} packages: resources for optimized storage
      and integrated traversal of annotated dense matrices.
AB  - Motivation: Facilitated by technological improvements, pharmacologic and genetic
      perturbational datasets have grown in recent years to include millions of
      experiments. Sharing these diverse data creates many opportunities for discovery,
      but the unprecedented size of data generated and its complex associated metadata
      have created data storage and integration challenges. Results: We present the
      GCTx file format and a suite of open-source packages for the efficient storage,
      serialization, and analysis of dense two-dimensional matrices. We have
      extensively used the format in the Connectivity Map to assemble and share massive
      data sets comprising 1.3 million experiments, and we anticipate that the format's
      generalizability, paired with code libraries that we provide, will lower barriers
      for integrated cross-assay analysis and algorithm development. Availability:
      Software packages (available in Python, R, Matlab, and Java) are freely available
      at https://github.com/cmap. Additional instructions, tutorials, and datasets are
      available at clue.io/code.

PMID- 30203023
TI  - Dante: genotyping of known complex and expanded short tandem repeats.
AB  - Motivation: Short tandem repeats (STRs) are stretches of repetitive DNA in which
      short sequences, typically made of 2-6 nucleotides, are repeated several times.
      Since STRs have many important biological roles and also belong to the most
      polymorphic parts of the human genome, they became utilized in several molecular
      genetic applications. Precise genotyping of STR alleles, therefore, was of high
      relevance during the last decades. Despite this, massively parallel sequencing
      (MPS) still lacks the analysis methods to fully utilize the information value of
      STRs in genome scale assays. Results: We propose an alignment-free algorithm,
      called Dante, for genotyping and characterization of STR alleles at user
      specified known loci based on sequence reads originating from STR loci of
      interest. The method accounts for natural deviations from the expected sequence,
      such as variation in the repeat count, sequencing errors, ambiguous bases, and
      complex loci containing several different motifs. In addition, we implemented a
      correction for copy number defects caused by the polymerase induced stutter
      effect as well as a prediction of STR expansions that, according to the
      conventional view, cannot be fully captured by inherently short MPS reads. We
      tested Dante on simulated data sets and on data sets obtained by targeted
      sequencing of protein coding parts of thousands of selected clinically relevant
      genes. In both these data sets, Dante outperformed HipSTR and GATK genotyping
      tools. Furthermore, Dante was able to predict allele expansions in all tested
      clinical cases. Availability: Dante is open source software, freely available for
      download at https://github.com/jbudis/dante. Supplementary Information:
      Supplementary data are available at Bioinformatics online.

PMID- 30203024
TI  - Variability of ciprofloxacin pharmacokinetics in children: impact on dose range
      in sickle cell patients.
AB  - Objectives: To determine the ciprofloxacin population pharmacokinetics in
      paediatric patients and the impact of underlying disease and evaluate the
      appropriateness of current dosage regimens. Patients and methods: Plasma
      concentrations of ciprofloxacin from children treated with ciprofloxacin were
      measured by HPLC. The pharmacokinetic population analysis was performed using
      NONMEM v7.2 (Icon Development Solutions, USA). Results: Two datasets were
      combined and 128 plasma concentrations in 60 patients aged 5.6 years (range 0.3
      18.9), treated with a median daily dose of 30.0 mg/kg (range 6.5-52.0) presenting
      with sickle cell disease (SCD; n = 20, 33%), haemopathy (n = 15, 25%), cystic
      fibrosis (CF; n = 3, 5%) and other diseases (n  =  22, 37%) were analysed. Data
      were best described by a two-compartment model with first-order elimination.
      Ciprofloxacin clearance (mean +/-  SD) was 0.81 +/- 0.30 L/h/kg, increased
      allometrically with weight, decreased with increasing creatinine concentration,
      was 89% higher in SCD compared with non-SCD patients and increased by 0.95 L/h/kg
      per year of age. The volume of distribution was 6.9 L/kg and depended only on the
      weight. Monte Carlo simulations were performed separately in SCD and non-SCD
      patients to target an AUC/MIC ratio >125 at steady-state, required for
      antibacterial efficacy, and recommendations of dosing regimens were proposed.
      Conclusions: In addition to known covariates, ciprofloxacin clearance is greater
      in SCD children compared with non-SCD patients. The dosing of this agent needs to
      be adapted to this subgroup of patients.

PMID- 30203025
TI  - A review of the impact of physical activity mass media campaigns on low compared
      to high socioeconomic groups.
AB  - Physical inactivity is a major contributor to non-communicable disease and people
      of low socioeconomic status (SES) are more likely to be insufficiently active.
      Physical activity mass media campaigns aim to increase physical activity
      participation, but little is known about their impact on low SES groups. We
      reviewed the published literature from 1990 to June 2016 to identify reports of
      physical activity mass media campaigns. We documented evaluation/study design,
      target population, campaign outcomes assessed, SES measures used and analysed the
      results of the SES comparisons. A total of 23 papers were reviewed, reporting on
      17 physical activity campaigns and 12 campaigns compared SES differences for 85
      outcomes: 45 comparisons showed no difference between lowest and highest SES
      groups, 20 showed a better outcome for the lowest SES group and 20 showed a worse
      outcome. Some campaigns found inconsistent results, but seven found only equal
      and/or better results for low SES groups. Post-campaign physical activity
      behaviour most commonly showed no SES differences, but no other patterns were
      seen. Our review found that physical activity mass media campaigns have mostly
      equitable or better impacts for low SES groups, but to reduce inequalities these
      campaigns need to be maximally effective for low SES populations.

PMID- 30203026
TI  - Dual functions of eicosapentaenoic acid-rich microalgae: enrichment of yolk with
      n-3 polyunsaturated fatty acids and partial replacement for soybean meal in diet
      of laying hens.
AB  - Microalgae (Nannochloropsis sp., NS), with high contents of eicosapentaenoic acid
      (EPA) and crude protein, may be one of the important n-3 polyunsaturated fatty
      acid (PUFA) sources and potential protein feed ingredient. The purposes of this
      study were to enrich yolk with n-3 PUFA by dietary EPA-rich NS supplementation
      and to evaluate whether it is feasible to partly substitute for soybean meal in
      laying hens diet. A total of 360 37-wk-old healthy Lohmann Brown laying hens,
      with similar laying rate and body weight, were randomly allotted to 5 groups (6
      replicates, 12 birds/replicate) and fed 5 experimental diets (0, 1, 2, 4, and 8%
      NS) for 4 wk. The hen performance and egg quality (except yolk color) were not
      affected (P > 0.05) by the NS supplemental diets. Yolk color score was increased
      as NS supplementation in diets (P < 0.001), and peaked on about the seventh day
      in all NS supplemental groups. The concentration of total n-3 PUFA was increased
      (P < 0.001), while total n-6 PUFA and n-6/n-3 ratio were decreased (P < 0.001) in
      yolk with increasing NS levels in diets. The 8% NS group had highest
      docosahexaenoic acid (DHA) and total n-3 PUFA levels, reaching 111.6 mg DHA and
      148.6 mg total n-3 PUFA per egg. Maximum DHA, total n-3 PUFA, very long-chain (LC
      ) n-3 PUFA, and LC-PUFA levels were all observed at day 13 of NS supplementation.
      In conclusion, dietary NS supplementation enriched yolk with n-3 PUFA (especially
      DHA) and enhanced yolk color score without adverse effects on performance and egg
      quality, and indicated the practical feasibility of partial replacement for
      soybean meal in laying hens diet.

PMID- 30203028
TI  - Erratum.

PMID- 30203027
TI  - Persistent mesorectal inflammatory activity is associated with complications
      after proctectomy in Crohn's Disease.
AB  - Background and Aims: Rectal resection in inflammatory bowel disease (IBD) is
      frequently complicated by disturbed perineal wound healing. Close rectal
      dissection, where the mesorectum remains in situ, is hypothesized to reduce
      complications by minimizing dead space, compared to total mesorectal excision.
      The aim of this study was to analyse post-operative outcomes of both techniques.
      In addition, immune-activity in mesorectal tissue was assessed. Methods: Perineal
      complications and healing were retrospectively assessed in a series of 74 IBD
      patients undergoing proctectomy using close rectal dissection or total mesorectal
      excision. The mesorectums of 15 patients were analysed by FACS,
      immunofluorescence and in-situ hybridization. Based on the clinical and in vitro
      findings, a novel surgical approach for Crohn's patients with disturbed perineal
      healing after proctectomy was developed. Results: In Crohn's disease, perineal
      complications were more frequent after close rectal dissection than after total
      mesorectal excision (59.5% versus 17.6%;p=0.007) with lower healing rates (51.4%
      versus 88.2%;p=0.014). No differences were observed in ulcerative colitis. The
      mesorectal tissue in Crohn's disease contained enhanced numbers of TNFalpha
      producing CD14+ macrophages, with less expression of the wound-healing marker
      CD206. Based on these findings, mesorectal excision with omentoplasty was
      performed in 8 patients with perineal complications after close rectal
      dissection, resulting in complete perineal wound closure in 6 patients. Pro
      inflammatory characteristics remained present in the mesorectum after close
      rectal dissection in these patients. Conclusions: In Crohn's disease, close
      rectal dissection resulted in more perineal complications, associated with a pro
      inflammatory immune status of the mesorectal tissue. Excision of this pro
      inflammatory mesenteric tissue resulted in improved perineal healing rates.

PMID- 30203030
TI  - The MmpS6-MmpL6 operon is an oxidative stress response system providing selective
      advantage to Mycobacterium tuberculosis in stress.
AB  - The stress response adaptability of Mycobacterium tuberculosis (Mtb) is still
      unresolved. Here, we ascribe an important function to the MmpS6-MmpL6 operon in
      Mtb stress management. By using a novel promoter probe in a high throughput
      unbiased screen, we identified several quinones as potent inducers of the M6
      operon in addition to triclosan. Triclosan and plumbagin effectively altered the
      intracellular redox potential in Mtb suggestive of oxidative stress in bacteria.
      Presence of the functional M6 operon correlated with an enhanced ability of
      clinical strains to survive in the presence of triclosan. Similar to the addition
      of a powerful ROS quenching agent like N-Ac in the medium, introduction of the
      complete M6 operon was sufficient to increase tolerance of the M6- strains to
      triclosan and plumbagin by effectively ablating the change in intracellular redox
      potential of Mtb, signifying the importance of this operon in oxidative stress
      survival in mycobacteria.

PMID- 30203029
TI  - A Novel Self-Micro-Emulsifying Delivery System Enhances Enrichment of
      Eicosapentaenoic Acid and Docosahexaenoic Acid after Single and Repeated Dosing
      in Healthy Adults in a Randomized Trial.
AB  - Background: A self-micro-emulsifying delivery system (SMEDS) promotes spontaneous
      emulsification of omega-3 (n-3) ethyl esters (EEs) into microdroplets in the
      stomach. Objective: The objective was to compare the effect of SMEDS preparations
      of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) EEs with standard
      EEs on EPA and DHA concentrations in the bloodstream after a single dose and
      repeated daily dosing. Methods: Eighty healthy subjects aged 18-65 y were
      randomly assigned to SMEDS-EPA or EE-EPA (both providing more EPA than DHA) or
      SMEDS-DHA or EE-DHA (both providing more DHA than EPA). They consumed a single
      dose (1.23-1.33 g EPA+DHA) without a meal, and EPA and DHA were measured in
      plasma over the following 24 h. Participants continued to take a single dose each
      morning before breakfast for 12 wk. EPA and DHA were measured in fasting plasma,
      mononuclear cells (MNCs), and RBCs. Results: EPA and DHA were higher in plasma in
      the 24 h after a single dose of SMEDS-EPA or SMEDS-DHA than after consuming the
      comparator EE (P < 0.001 for both). Compared with the EE form, repeated daily
      dosing of the SMEDS formulations for 12 wk resulted in higher concentrations of
      EPA and DHA in plasma (P = 0.086 and 0.005, respectively), MNCs (P < 0.001 and
      0.020, respectively), and RBCs (both P < 0.001). The omega-3 index increased over
      12 wk from 5.1 +/- 0.9 to 7.9 +/- 0.9 in the SMEDS-EPA group, from 5.3 +/- 1.1 to
      9.0 +/- 1.2 in the SMEDS-DHA group, from 4.8 +/- 0.8 to 6.4 +/- 0.9 in the EE-EPA
      group, and from 5.2 +/- 0.9 to 7.2 +/- 1.0 in the EE-DHA group (all P < 0.001).
      The omega-3 index was higher with SMEDS than with the comparator EE at 12 wk
      (both P < 0.001). Conclusions: Compared with standard EEs, a SMEDS results in
      greater incorporation of EPA and DHA into blood pools after a single dose and
      with repeated daily dosing in healthy adults. A SMEDS enhances delivery of
      bioactive omega-3 fatty acids. This trial was registered at www.isrctn.com as
      ISRCTN96459690.

PMID- 30203032
TI  - Obesity and Central Blood Pressure in Children and Adolescents.

PMID- 30203031
TI  - The impact of generic labels on the consumption of and adherence to medication: a
      randomized controlled trial.
AB  - Background: Although generic drugs are pharmacologically equivalent to their
      brand-name counterparts, prejudices against them remain strong. We assess the
      extent to which generic (versus brand-name) labels affect patients' consumption
      of and adherence to medication. Methods: One hundred one patients who received
      dental implants agreed to participate in a study. In a pre-surgery survey, most
      patients reported a positive view about generic drugs. After dental surgery, the
      patients were prescribed a once-daily analgesic regimen (50 mg tramadol
      hydrochloride) for up to 7 days. All the patients received at no cost the same
      brand-name medication with either a brand-name label (n = 51) or a generic label
      (n = 50) and were informed of the retail prices associated with both labels.
      Telephone follow-up was conducted 24 hours, four days, and seven days after
      surgery to assess the number of prescribed pills consumed and when their use was
      discontinued, the number of non-prescribed pills consumed, pain levels throughout
      the follow-up period, the perceived efficacy of the analgesic, and the
      willingness to recommend it to a friend. Results: The label manipulation impacted
      the participants' behaviour and subjective assessments. Discontinuation before
      the end of the 7-day period was more frequent under the generic (vs. brand-name)
      label condition. The patients in the generic label group were also more likely to
      consume non-prescribed pills (non-adherence). Additionally, the patients in the
      generic label group reported higher levels of pain. Conclusion: Generic labels
      may negatively affect adherence to treatment even if patients report ex ante
      positive evaluations of the quality of generics drugs.

PMID- 30203033
TI  - Unusual rapid progression of non-bacterial thrombotic endocarditis in a patient
      with bladder cancer despite undergoing intensification treatment with rivaroxaban
      for acute venous thromboembolism.

PMID- 30203034
TI  - Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines
      on the Evaluation and Treatment of Patients with Thoracolumbar Spine Trauma:
      Operative Versus Nonoperative Treatment.
AB  - QUESTION 1: Does the surgical treatment of burst fractures of the thoracic and
      lumbar spine improve clinical outcomes compared to nonoperative treatment?
      RECOMMENDATION 1: There is conflicting evidence to recommend for or against the
      use of surgical intervention to improve clinical outcomes in patients with
      thoracolumbar burst fracture who are neurologically intact. Therefore, it is
      recommended that the discretion of the treating provider be used to determine if
      the presenting thoracic or lumbar burst fracture in the neurologically intact
      patient warrants surgical intervention. Strength of Recommendation: Grade
      Insufficient. QUESTION 2: Does the surgical treatment of nonburst fractures of
      the thoracic and lumbar spine improve clinical outcomes compared to nonoperative
      treatment? RECOMMENDATION 2: There is insufficient evidence to recommend for or
      against the use of surgical intervention for nonburst thoracic or lumbar
      fractures. It is recommended that the decision to pursue surgery for such
      fractures be at the discretion of the treating physician. Strength of
      Recommendation: Grade Insufficient The full version of the guideline can be
      reviewed at: https://www.cns.org/guideline-chapters/congress-neurological
      surgeons-systematic-review-evidence-based-guidelines/chapter_1.

PMID- 30203036
TI  - Social Media Use and Preferences in Patients With Inflammatory Bowel Disease.
AB  - Introduction: There has been growing interest in social media use in managing
      chronic illnesses. The aim of this study was to assess social media usage in a
      large sample of patients with inflammatory bowel disease (IBD). Methods: We
      performed a cross-sectional study within the Crohn's and Colitis Foundation's IBD
      Partners' internet-based cohort. We used bivariate analyses to compare patient
      characteristics by various factors associated with social media utilization. We
      used logistic regression models to determine factors independently associated
      with using social media to obtain IBD-related information. Results: A total of
      1960 IBD patients were included. Most respondents reported spending between 30
      and 60 minutes on social media sites per day. Thirty-two percent of respondents
      agreed that social media could be useful for disease management. Most respondents
      agreed that social media should be used to connect patients with IBD-related
      organizations and to obtain IBD-related information online. Fifty percent of
      respondents could not rate the quality of IBD information posted online. Concerns
      surrounding social media use included privacy/confidentiality and lack of trust
      of information posted. The most frequently used social media website was
      Facebook. Thirty-two percent of respondents used social media at least once in
      the last week to obtain or post IBD-related content. Factors independently
      associated with social media use for IBD included female gender (odds ratio [OR]
      1.43; 95% CI,1.10-1.87), age (OR 0.99; 95% CI, 0.98-1.00), remission (OR 0.63;
      95% CI, 0.50-0.79), and a diagnosis of Crohn's disease (CD) rather than
      ulcerative colitis (UC) (OR 0.74; 95% CI, 0.58-0.93). Conclusions: Patients with
      IBD in this cohort expressed a substantial interest in using social media to aid
      in disease management. Use was higher in younger patients, females, and patients
      with active disease. Most patients were unsure of the quality of information
      posted online, which represents opportunities for clinicians to guide patients to
      appropriate resources.

PMID- 30203037
TI  - Reply: Two cases of CLIPPERS with increased number of perivascular CD20-positive
      B lymphocytes.

PMID- 30203035
TI  - Small RNA sequences derived from pre-microRNAs in the supraspliceosome.
AB  - MicroRNAs (miRNAs) are short non-coding RNAs that negatively regulate the
      expression and translation of genes in healthy and diseased tissues. Herein, we
      characterize short RNAs from human HeLa cells found in the supraspliceosome, a
      nuclear dynamic machine in which pre-mRNA processing occurs. We sequenced small
      RNAs (<200 nt) extracted from the supraspliceosome, and identified sequences that
      are derived from 200 miRNAs genes. About three quarters of them are mature
      miRNAs, whereas the rest account for various defined regions of the pre-miRNA,
      and its hairpin-loop precursor. Out of these aligned sequences, 53 were
      undetected in cellular extract, and the abundance of additional 48 strongly
      differed from that in cellular extract. Notably, we describe seven abundant miRNA
      derived sequences that overlap non-coding exons of their host gene. The rich
      collection of sequences identical to pre-miRNAs at the supraspliceosome suggests
      overlooked nuclear functions. Specifically, the abundant hsa-mir-99b may affect
      splicing of LINC01129 primary transcript through base-pairing with its exon
      intron junction. Using suppression and overexpression experiments, we show that
      hsa-mir-7704 negatively regulates the level of the lncRNA HAGLR. We claim that in
      cases of extended base-pairing complementarity, such supraspliceosomal pre-miRNA
      sequences might have a role in transcription attenuation, maturation and
      processing.

PMID- 30203038
TI  - Challenging violence against women: a Scottish critical health literacy
      initiative.
AB  - Violence against women constitutes a significant public health problem affecting
      an estimated 35% of women worldwide (WHO, 2013); the scale of the problem and its
      ongoing intransigence indicate the need for critical and transformative
      approaches that confront the cultures that support gender violence and lead to
      change. The present paper analyses a program run in Scottish primary schools for
      10-12 year olds called RESPECT that was successful in making pupils alert to and
      critical of gendering norms and practices. Analysis reveals that the teaching
      plans and activities of RESPECT are highly consistent with a critical pedagogical
      approach (Freire, 2005; Matthews, 2014), and indicates the value of combining the
      theoretical approaches of critical pedagogy, feminism and critical health
      literacy in public health campaign materials aimed at challenging the cultural
      bases of gender violence in ways that promote health in an educational setting.

PMID- 30203039
TI  - Diagnostic FDG PET/CT findings in Polymyalgia Rheumatica.

PMID- 30203040
TI  - Expanding the Spectrum of Robotic Assistance in Cranial Neurosurgery.
AB  - BACKGROUND: Robotic automation and haptic guidance have multiple applications in
      neurosurgery. OBJECTIVE: To define the spectrum of cranial procedures potentially
      benefiting from robotic assistance in a university hospital neurosurgical
      practice setting. METHODS: Procedures utilizing robotic assistance during a 24-mo
      period were retrospectively analyzed and classified as stereotactic or endoscopic
      based on the mode utilized in the ROSA system (Zimmer Biomet, Warsaw, Indiana).
      Machine log file data were retrospectively analyzed to compare registration
      accuracy using 3 different methods: (1) facial laser scanning, (2) bone
      fiduciary, or (3) skin fiduciary. RESULTS: Two hundred seven cranial
      neurosurgical procedures utilizing robotic assistance were performed in a 24-mo
      period. One hundred forty-five procedures utilizing the stereotactic mode
      included 33% stereotactic biopsy, 31% Stereo-EEG electrode insertion, 20% cranial
      navigation, 7% stereotactic catheter placement, 6% craniofacial stereotactic wire
      placement, 2% deep brain stimulation lead placement, and 1% stereotactic
      radiofrequency ablation. Sixty-two procedures utilizing the haptic endoscope
      guidance mode consisted of 48% transnasal endoscopic, 29% ventriculoscopic, and
      23% endoport tubular access. Statistically significant differences in
      registration accuracies were observed with 0.521 +/- 0.135 mm (n = 132) for
      facial laser scanning, 1.026 +/- 0.398 mm for bone fiduciary (n = 22), and 1.750
      +/- 0.967 mm for skin fiduciary (n = 30; ANOVA, P < .001). CONCLUSION: The
      combination of accurate, automated stereotaxy with image and haptic guidance can
      be applied to a wide range of cranial neurosurgical procedures. The facial laser
      scanning method offered the best registration accuracy for the ROSA system based
      on our retrospective analysis.

PMID- 30203041
TI  - Combined Analysis of GAD65, miR-375 and Unmethylated Insulin DNA Following Islet
      Transplantation in T1D Patients.
AB  - Aim: several biomarkers were proposed to detect pancreatic beta cell destruction
      in vivo but were so far not compared for sensitivity and significance. Methods:
      we used islet transplantation as model to compare plasma concentrations of miR
      375, GAD65 and (un)methylated insulin DNA, measured at subpicomolar sensitivity,
      to study their discharge kinetics, power for outcome prediction and detection of
      graft loss during follow-up. Results: at 60 min post-transplantation, GAD65 and
      miR-375 consistently showed near-equimolar and correlated increases, proportional
      to the number of implanted beta cells. GAD65 and miR-375 showed comparable power
      to predict poor graft outcome at 2 months, with AUC respectively of 0.833 and
      0.771 (p=0.53). Using ROC analysis we defined likelihood ratios (LRs) for
      rationally selected result intervals: in GADA-negative recipients (N=28), GAD65
      <4.5 pmol/l (LR=0.15) and >12.2 pmol/l (LR=infinity) respectively predicted good
      and poor outcome. miR-375 could be used in all recipients irrespective of GADA
      status (N=46), with levels <1.4 pmol/l (LR=0.14) or >7.6 pmol/l (LR=9.53) as dual
      thresholds. The post-transplant surge of (un)methylated insulin DNA was
      inconsistent and unrelated to outcome. Combined measurement of these 3 biomarkers
      was also tested as liquid biopsy for beta cell death during 2 month follow-up:
      incidental surges of GAD65, miR-375 and (un)methylated insulin DNA, alone or
      combined, were confidently detected but could not be related to outcome.
      Conclusions: GAD65 and miR-375 perform equally well to quantify early graft
      destruction and to predict graft outcome, outperforming unmethylated insulin DNA.

PMID- 30203042
TI  - Structural Characterization of Pan-ebolavirus Antibody 6D6 Targeting the Fusion
      Peptide of the Surface Glycoprotein.
AB  - Ebola virus infection causes severe disease in humans and represents a global
      health threat. Candidates for immunotherapeutics and vaccines have shown promise
      in clinical trials, though they are ineffective against other members of the
      Ebolavirus genus which also cause periodic, lethal outbreaks. Here, we present a
      crystal structure of a pan-ebolavirus antibody, 6D6, as well as single particle
      electron microscopy reconstructions of 6D6 in complex with Ebola and Bundibugyo
      virus glycoproteins. 6D6 binds to the conserved glycoprotein fusion peptide,
      implicating it as a site of immune vulnerability that could be exploited to
      reliably elicit a pan-ebolavirus neutralizing antibody response.

PMID- 30203043
TI  - Reconsidering aetiologies of type 2 myocardial infarction: when a classification
      is a simplistic approach for a complex reality.

PMID- 30203044
TI  - Efficacy and Phytotoxicity of Phosphine as Fumigants for Frankliniella
      occidentalis (Thysanoptera: Thripidae) on Asparagus.
AB  - The insecticidal activity of phosphine (PH3) and ethyl formate (EF) toward
      Frankliniella occidentalis (Pergande) (Thysanoptera: Thripidae) and their
      phytotoxicity to asparagus were evaluated. Both the PH3 and EF fumigants showed
      higher lethal concentration and time (LCT) values at lower temperatures. The
      LCT99 values of PH3 and EF at 5 degrees C in a 12 liters desiccator for 4 h
      showed the following ranking: eggs (64.69 mg.h/liter for PH3 and EF indicating
      phytotoxicity to asparagus), nymphs (5.54 and 17.48 mg.h/liter, respectively),
      and adults (3.83 and 14.67 mg.h/liter, respectively). The adsorption of PH3 was
      approximately 11% at 2 degrees C and 13% at 5 degrees C, whereas the adsorption
      of EF increased sharply to 88% at 2 degrees C and 97% at 5 degrees C. The
      hatching rate of F. occidentalis eggs was approximately 95% at all locations
      (top, middle, and bottom) in the presence of 4 mg/liter PH3 at 5 degrees C in a
      0.65-m3 fumigation chamber for 24 h. However, extension of the treatment to 48 h
      resulted in 100% inhibition of egg hatching. The atmospheric level of PH3
      decreased below the threshold limit value after 80 min, and phytotoxicity was not
      observed. The results revealed that EF is highly absorbed by asparagus and is not
      suitable as a fumigant, but PH3 is a suitable alternative to the fumigant methyl
      bromide for the control of western flower thrips in asparagus.

PMID- 30203045
TI  - Immunological differences between primary and metastatic breast cancer.
AB  - Background: Little is known about how the immune microenvironment of breast
      cancer evolves during disease progression. Patients and methods: We compared
      tumor infiltrating lymphocyte (TIL) count, PD-L1 protein expression by
      immunohistochemistry and mRNA levels of 730 immune-related genes using Nanostring
      technology in primary and metastatic cancer samples. Results: TIL counts and PD
      L1 positivity were significantly lower in metastases. Immune cell metagenes
      corresponding to CD8, T-helper, T-reg, Cytotoxic T, Dendritic and Mastoid cells,
      and expression of 13 of 29 immuno-oncology therapeutic targets in clinical
      development including PD1, PD-L1, and CTLA4 were significantly lower in
      metastases. There was also coordinated down regulation of chemoattractant
      ligand/receptor pairs (CCL19/CCR7, CXCL9/CXCR3, IL15/IL15R), interferon regulated
      genes (STAT1, IRF-1,-4,-7, IFI-27,-35), granzyme/granulysin, MHC class I and
      immune proteasome (PSMB-8,-9,-10) expression in metastases. Immunotherapy
      response predictive signatures were also lower. The expression of macrophage
      markers (CD163, CCL2/CCR2, CSF1/CSFR1, CXCR4/CXCL12), pro-tumorigenic toll like
      receptor pathway genes (CD14/TLR-1,-2,-4,-5,-6/MyD88), HLA-E, ecto-nuclease
      CD73/NT5E and inhibitory complement receptors (CD-59,-55,-46) remained high in
      metastases and represent potential therapeutic targets. Conclusions: Metastatic
      breast cancers are immunologically more inert than the corresponding primary
      tumors but some immune-oncology targets and macrophage and angiogenesis
      signatures show preserved expression and suggest therapeutic combinations for
      clinical testing.

PMID- 30203046
TI  - Chemical Activation of the Constitutive Androstane Receptor (CAR) Leads to
      Activation of Oxidant-Induced Nrf2.
AB  - Exposure to environmentally-relevant chemicals that activate the xenobiotic
      receptors aryl hydrocarbon receptor (AhR), constitutive androstane receptor
      (CAR), and peroxisome proliferator-activated receptor alpha (PPARalpha) in rodent
      test systems often leads to increases in oxidative stress (OS) that contributes
      to liver cancer induction. We hypothesized that activation of the oxidant-induced
      transcription factor Nrf2 could be used as a surrogate endpoint for increases in
      OS. We examined the relationships between activation of xenobiotic receptors and
      Nrf2 using previously characterized gene expression biomarkers that accurately
      predict modulation. Using a correlation approach (Running Fisher Test), the
      biomarkers were compared to microarray profiles in a mouse liver gene expression
      compendium. Out of the 163 chemicals examined, 47% from 53 studies activated
      Nrf2. We found consistent coupling between CAR and Nrf2 activation. Out of the 41
      chemicals from 32 studies that activated CAR, 90% also activated Nrf2. CAR was
      activated earlier and at lower doses than Nrf2, indicating CAR activation
      preceded Nrf2 activation. Nrf2 activation by two CAR activators was abolished in
      CAR-null mice. We hypothesized that Nrf2 is activated by ROS from the increased
      activity of enzymes encoded by Cyp2b family members. However, Nrf2 was similarly
      activated in the livers of both TCPOBOP-treated wild-type and Cyp2b9/10/13-null
      mice. This study provides evidence that Nrf2 activation 1) often occurs after
      exposure to xenobiotic chemicals, 2) is tightly linked to activation of CAR, and
      3) does not require induction of three Cyp2b genes secondary to CAR activation.

PMID- 30203047
TI  - Pancan-meQTL: a database to systematically evaluate the effects of genetic
      variants on methylation in human cancer.
AB  - DNA methylation is an important epigenetic mechanism for regulating gene
      expression. Aberrant DNA methylation has been observed in various human diseases,
      including cancer. Single-nucleotide polymorphisms can contribute to tumor
      initiation, progression and prognosis by influencing DNA methylation, and DNA
      methylation quantitative trait loci (meQTL) have been identified in physiological
      and pathological contexts. However, no database has been developed to
      systematically analyze meQTLs across multiple cancer types. Here, we present
      Pancan-meQTL, a database to comprehensively provide meQTLs across 23 cancer types
      from The Cancer Genome Atlas by integrating genome-wide genotype and DNA
      methylation data. In total, we identified 8 028 964 cis-meQTLs and 965 050 trans
      meQTLs. Among these, 23 432 meQTLs are associated with patient overall survival
      times. Furthermore, we identified 2 214 458 meQTLs that overlap with known loci
      identified through genome-wide association studies. Pancan-meQTL provides a user
      friendly web interface (http://bioinfo.life.hust.edu.cn/Pancan-meQTL/) that is
      convenient for browsing, searching and downloading data of interest. This
      database is a valuable resource for investigating the roles of genetics and
      epigenetics in cancer.

PMID- 30203049
TI  - Developing synthetic hybrid promoters to increase constitutive or diauxic shift
      induced expression in Saccharomyces cerevisiae.
AB  - Fine-tuning of the expression of genes is crucial for cell factory construction.
      Promoters are the most important tools to control gene expression. However,
      native promoters are often limited by their transcriptional ability. In this
      study, we sought to overcome the limitations of native promoters in Saccharomyces
      cerevisiae through the construction of hybrid promoter libraries for both
      constitutive promoters and promoters induced by diauxic shift. A series of hybrid
      constitutive promoters were constructed by combing the upstream activation
      sequences and changing the core promoter elements. The transcriptional capacity
      of the strongest promoter was 2-fold higher than that of the yeast native TEF1
      promoter. Aside from the constitutive promoters, hybrid promoters that were
      induced in the post-diauxic phase were also constructed. These promoters had low
      transcriptional ability during growth on glucose and automatically activated upon
      growth with a diauxic shift. The strength of these promoters was also increased
      by replacing the core promoter with strong core promoters. Our study provides a
      series of constitutive and diauxic shift-induced promoters with a broad range of
      transcriptional capacity and will facilitate synthetic biology and metabolic
      engineering application.

PMID- 30203048
TI  - Dot1 promotes H2B ubiquitination by a methyltransferase-independent mechanism.
AB  - The histone methyltransferase Dot1 is conserved from yeast to human and
      methylates lysine 79 of histone H3 (H3K79) on the core of the nucleosome. H3K79
      methylation by Dot1 affects gene expression and the response to DNA damage, and
      is enhanced by monoubiquitination of the C-terminus of histone H2B (H2Bub1). To
      gain more insight into the functions of Dot1, we generated genetic interaction
      maps of increased-dosage alleles of DOT1. We identified a functional relationship
      between increased Dot1 dosage and loss of the DUB module of the SAGA co-activator
      complex, which deubiquitinates H2Bub1 and thereby negatively regulates H3K79
      methylation. Increased Dot1 dosage was found to promote H2Bub1 in a dose
      dependent manner and this was exacerbated by the loss of SAGA-DUB activity, which
      also caused a negative genetic interaction. The stimulatory effect on H2B
      ubiquitination was mediated by the N-terminus of Dot1, independent of
      methyltransferase activity. Our findings show that Dot1 and H2Bub1 are subject to
      bi-directional crosstalk and that Dot1 possesses chromatin regulatory functions
      that are independent of its methyltransferase activity.

PMID- 30203050
TI  - Synthetic control systems for high performance gene expression in mammalian
      cells.
AB  - Tunable induction of gene expression is an essential tool in biology and
      biotechnology. In spite of that, current induction systems often exhibit
      unpredictable behavior and performance shortcomings, including high sensitivity
      to transactivator dosage and plasmid take-up variation, and excessive consumption
      of cellular resources. To mitigate these limitations, we introduce here a novel
      family of gene expression control systems of varying complexity with
      significantly enhanced performance. These include: (i) an incoherent feedforward
      circuit that exhibits output tunability and robustness to plasmid take-up
      variation; (ii) a negative feedback circuit that reduces burden and provides
      robustness to transactivator dosage variability; and (iii) a new hybrid circuit
      integrating negative feedback and incoherent feedforward that combines the
      benefits of both. As with endogenous circuits, the complexity of our genetic
      controllers is not gratuitous, but is the necessary outcome of more stringent
      performance requirements. We demonstrate the benefits of these controllers in two
      applications. In a culture of CHO cells for protein manufacturing, the circuits
      result in up to a 2.6-fold yield improvement over a standard system. In human
      induced pluripotent stem cells they enable precisely regulated expression of an
      otherwise poorly tolerated gene of interest, resulting in a significant increase
      in the viability of the transfected cells.

PMID- 30203051
TI  - Role of type 2A phosphatase regulatory subunit B56alpha in regulating cardiac
      responses to beta-adrenergic stimulation in vivo.
AB  - Aims: B56alpha is a protein phosphatase 2A (PP2A) regulatory subunit that is
      highly expressed in the heart. We previously reported that cardiomyocyte B56alpha
      localises to myofilaments under resting conditions and translocates to the
      cytosol in response to acute beta-adrenergic receptor (beta-AR) stimulation.
      Given the importance of reversible protein phosphorylation in modulating cardiac
      function during sympathetic stimulation, we hypothesised that loss of B56alpha in
      mice with targeted disruption of the gene encoding B56alpha (Ppp2r5a) would
      impact on cardiac responses to beta-AR stimulation in vivo. Methods and results:
      Cardiac phenotype of mice heterozygous (HET) or homozygous (HOM) for the
      disrupted Ppp2r5a allele and wildtype (WT) littermates was characterised under
      basal conditions and following acute beta-AR stimulation with dobutamine (DOB;
      0.75 mg/kg i.p.) or sustained beta-AR stimulation by 2-week infusion of
      isoproterenol (ISO; 30 mg/kg/day s.c.). Left ventricular (LV) wall thicknesses,
      chamber dimensions and function were assessed by echocardiography, and heart
      tissue collected for gravimetric, histological and biochemical analyses. Western
      blot analysis revealed partial and complete loss of B56alpha protein in hearts
      from HET and HOM mice, respectively, and no changes in the expression of other
      PP2A regulatory, catalytic or scaffolding subunits. PP2A catalytic activity was
      reduced in hearts of both HET and HOM mice. There were no differences in the
      basal cardiac phenotype between genotypes. Acute DOB stimulation induced the
      expected inotropic response in WT and HET mice, which was attenuated in HOM mice.
      By contrast, DOB-induced increases in heart rate were unaffected by B56alpha
      deficiency. In WT mice, ISO infusion increased LV wall thicknesses, cardiomyocyte
      area and ventricular mass, without LV dilation, systolic dysfunction, collagen
      deposition or foetal gene expression. The hypertrophic response to ISO was
      blunted in mice deficient for B56alpha. Conclusions: These findings identify
      B56alpha as a potential regulator of cardiac structure and function during beta
      AR stimulation.

PMID- 30203053
TI  - Pain Self-Management: Easier Said than Done? Factors Associated with Early
      Dropout from Pain Self-Management in a Rural Primary Care Population.
AB  - Objective: To explore whether psychosocial or demographic factors are associated
      with early dropout from pain self-management in a rural, low-socioeconomic status
      population. Design: Secondary analysis of retrospective data. Setting:
      Multidisciplinary pain clinic located in an outer regional area of Australia.
      Subjects: One hundred eighty-six people attending a public community health
      center with chronic noncancer pain (mean age 54.9 years; 58.1% women; 81.7% in
      receipt of government benefit as their primary source of income). Methods:
      Bivariate analysis and logistic regression, with early dropout as the dependent
      variable and a range of demographic and psychological independent variables.
      Results: Following bivariate analysis, early dropout was significantly associated
      (P < 0.05) with male gender, younger age, history of substance use, being a past
      victim of assault/abuse, receiving unemployment or disability benefit, having
      literacy difficulties, higher pain catastrophizing score, higher daily opioid
      dose, and not holding a multifactorial belief about the cause of pain. Logistic
      regression analysis resulted in three significant predictors of dropout:
      substance use history (P = 0.002), past victim of assault or abuse (P = 0.029),
      high pain catastrophising score (P = 0.048); and one of engagement: holding a
      multifactorial belief about pain cause (P = 0.005). Conclusions: In a rural, low
      socioeconomic status population, addressing social stressors related to lifetime
      adversity may be important to increasing engagement in pain self-management. Lack
      of attention to these factors may increase health inequity among those most
      disabled by chronic pain. Further research into dropout and engagement,
      especially among disadvantaged populations, is recommended.

PMID- 30203054
TI  - Therapeutic Applications of Nicotinic Stimulation: Successes, Failures, and
      Future Prospects.

PMID- 30203055
TI  - Title: Interferon tau-dependent and independent effects of the bovine conceptus
      on the endometrial transcriptome.
AB  - This study investigated bovine conceptus-induced modifications to the endometrial
      transcriptome related to effects of interferon tau (IFNT), conceptus origin (in
      vivo vs. in vitro) and conceptus sex. In vitro (IVF) or in vivo (superovulation
      and artificial insemination, AI) produced blastocysts were transferred into
      recipient heifers on Day 7 of the estrous cycle. On Day 15, IVF- or AI-derived
      conceptuses were obtained by uterine flushing and individually placed on
      endometrial explants in media for 6 h. Explants were also cultured with media
      alone as a control or media containing 100 ng/mL IFNT. Total explant RNA was
      analyzed by RNA-Seq. Incubation of endometrium with IFNT or IVF- or AI-derived
      conceptuses changed (P <= 0.001) expression of 491, 498 and 576 transcripts,
      respectively, compared to the control. Further, 369 differentially expressed
      genes (DEGs) were common between explants exposed to IFNT or a conceptus. 240
      DEGs were uniquely altered by conceptuses (IVF- and AI-derived) but not IFNT. Of
      these transcripts, 46 were shared between the IVF and AI groups, while 61 and 133
      were specific to IVF and AI conceptuses, respectively. Five genes (MLPH, PROM2,
      MYADM, VN1R4L, HTR1A) were more abundant in endometrium exposed to female
      compared to male conceptuses (P < 0.001). A single gene (ARL4C) was more abundant
      in response to male conceptuses (P < 0.001) than female conceptuses. These data
      support the hypothesis that conceptus regulation of gene expression in the
      endometrium is complex and involves factors other than IFNT that may have a
      biological role in pregnancy establishment.

PMID- 30203057
TI  - Can we remove scar and fibrosis from adult human myocardium?
AB  - The pathological processes leading to heart failure are characterized by the
      formation of fibrosis and scar, yet the dynamics of scar production and removal
      are incompletely understood. Spontaneous disappearance of myocardial collagen is
      reported in infancy but doubted in adulthood where scar volume constitutes a
      better prognostic indicator than the conventional parameters of ventricular
      function. Whilst certain drugs are known to attenuate myocardial fibrosis
      evidence is emerging that stem cell therapy also has the potential to reduce scar
      size and improve myocardial viability. Both animal studies and clinical trials
      support the concept that, as in infancy, cellular processes can be triggered to
      remove collagen and regenerate injured myocardium. The molecular mechanisms
      likely involve anti-fibrotic cytokines growth factors and matrix
      metalloproteinases. Autologous cardiac, bone-marrow and adipose tissue derived
      stem cells have each shown efficacy. Specific immune privileged mesenchymal stem
      cells and genetically modified immunomodulatory progenitor cells may in turn
      provide an allogenic source for the paracrine effects. Thus autologous and
      allogenic cells both have the potential through paracrine action to reduce scar
      volume, boost angiogenesis and improve ventricular morphology. The potential
      benefit of myocardial cell therapy for routine treatment of heart failure is an
      area that requires further study.

PMID- 30203058
TI  - Missing data and prediction: the pattern submodel.
AB  - Missing data are a common problem for both the construction and implementation of
      a prediction algorithm. Pattern submodels (PS)-a set of submodels for every
      missing data pattern that are fit using only data from that pattern-are a
      computationally efficient remedy for handling missing data at both stages. Here,
      we show that PS (i) retain their predictive accuracy even when the missing data
      mechanism is not missing at random (MAR) and (ii) yield an algorithm that is the
      most predictive among all standard missing data strategies. Specifically, we show
      that the expected loss of a forecasting algorithm is minimized when each pattern
      specific loss is minimized. Simulations and a re-analysis of the SUPPORT study
      confirms that PS generally outperforms zero-imputation, mean-imputation, complete
      case analysis, complete-case submodels, and even multiple imputation (MI). The
      degree of improvement is highly dependent on the missingness mechanism and the
      effect size of missing predictors. When the data are MAR, MI can yield comparable
      forecasting performance but generally requires a larger computational cost. We
      also show that predictions from the PS approach are equivalent to the limiting
      predictions for a MI procedure that is dependent on missingness indicators (the
      MIMI model). The focus of this article is on out-of-sample prediction;
      implications for model inference are only briefly explored.

PMID- 30203059
TI  - Effect of Environmental Temperature on Serum Sodium Level in Hospitalized Non
      critically Ill Children.
AB  - Background: Intravenous hypotonic fluid administered in children is associated
      with an increased risk of developing hyponatremia. This finding has been reported
      from temperate countries where climate is relatively cold. But whether this risk
      also occurs in tropical countries has not been elucidated. Objective: The
      objective of this study was to determine the relationship between environmental
      temperature and serum sodium in non-critically ill children. Methods: A
      retrospective study. Results: A total of 1061 hospitalized children were
      enrolled. Incidences of hyponatremia were not different between patients who
      received isotonic and hypotonic fluids (29% vs. 31%). Subgroup analysis showed a
      trend of higher incidence of hyponatremia in patients who received hypotonic
      fluid than isotonic fluid only in patients admitted to the air-conditioned wards
      (29% vs. 21%, p = 0.08). Conclusion: Children admitted to the air-conditioned
      wards who received hypotonic fluid seemed to carry a higher risk of developing
      hyponatremia than those admitted to the non-air-conditioned ward.

PMID- 30203052
TI  - Developing a toolkit for the assessment and monitoring of musculoskeletal ageing.
AB  - The complexities and heterogeneity of the ageing process have slowed the
      development of consensus on appropriate biomarkers of healthy ageing. The Medical
      Research Council-Arthritis Research UK Centre for Integrated research into
      Musculoskeletal Ageing (CIMA) is a collaboration between researchers and
      clinicians at the Universities of Liverpool, Sheffield and Newcastle. One of
      CIMA's objectives is to 'Identify and share optimal techniques and approaches to
      monitor age-related changes in all musculoskeletal tissues, and to provide an
      integrated assessment of musculoskeletal function'-in other words to develop a
      toolkit for assessing musculoskeletal ageing. This toolkit is envisaged as an
      instrument that can be used to characterise and quantify musculoskeletal function
      during 'normal' ageing, lend itself to use in large-scale, internationally
      important cohorts, and provide a set of biomarker outcome measures for
      epidemiological and intervention studies designed to enhance healthy
      musculoskeletal ageing. Such potential biomarkers include: biochemical
      measurements in biofluids or tissue samples, in vivo measurements of body
      composition, imaging of structural and physical properties, and functional tests.
      This review assesses candidate biomarkers of musculoskeletal ageing under these
      four headings, details their biological bases, strengths and limitations, and
      makes practical recommendations for their use. In addition, we identify gaps in
      the evidence base and priorities for further research on biomarkers of
      musculoskeletal ageing.

PMID- 30203056
TI  - Novel public-private partnerships to address the double burden of malnutrition.
AB  - Public-private partnerships are an effective way to address the global double
      burden of malnutrition. While public-private partnerships operate in multiple
      forms, their leadership usually falls to governments, public health agencies, or
      nongovernmental organizations, with the private sector taking a subordinate role.
      The rapid ascent of social media and mass communications worldwide has provided a
      disruptive technology for new nutrition intervention programs. A new model,
      provisionally called private-public engagement, takes advantage of social media,
      mass media, and integrated social marketing to reach parents, families, and
      communities directly. These new private-public engagement initiatives need to be
      managed in ways suggested for public-private partnerships by the World Health
      Organization, especially if the private sector is in the lead. Once the rationale
      for engagement is defined, there is a need to mobilize resources, establish in
      country partnerships and codes of conduct, and provide a plan for monitoring,
      evaluation, and accountability. Provided here is an example consistent with the
      private-public engagement approach, ie, the United for Healthier Kids program,
      which has been aimed at families with children aged less than 12 years. Materials
      to inspire behavioral change and promote healthier diets and lifestyle were
      disseminated in a number of countries through both digital and physical channels,
      often in partnership with local or regional governments. A description of this
      program, along with strategies to promote transparency and communication among
      stakeholders, serves to provide guidance for the development of future effective
      private-public engagements.

PMID- 30203061
TI  - A murmur in an asymptomatic 60-year-old woman: a rare presentation of ALCAPA
      syndrome.

PMID- 30203060
TI  - Inflammasomes: An Emerging Mechanism Translating Environmental Toxicant Exposure
      Into Neuroinflammation in Parkinson's Disease.
AB  - Evidence indicates that complex gene-environment interactions underlie the
      incidence and progression of Parkinson's disease (PD). Neuroinflammation is a
      well-characterized feature of PD widely believed to exacerbate the
      neurodegenerative process. Environmental toxicants associated with PD, such as
      pesticides and heavy metals, can cause cellular damage and stress potentially
      triggering an inflammatory response. Toxicant exposure can cause stress and
      damage to cells by impairing mitochondrial function, deregulating lysosomal
      function, and enhancing the spread of misfolded proteins. These stress-associated
      mechanisms produce sterile triggers such as reactive oxygen species (ROS) along
      with a variety of proteinaceous insults that are well documented in PD. These
      associations provide a compelling rationale for analysis of sterile inflammatory
      mechanisms that may link environmental exposure to neuroinflammation and PD
      progression. Intracellular inflammasomes are cytosolic assemblies of proteins
      that contain pattern recognition receptors, and a growing body of evidence
      implicates the association between inflammasome activation and neurodegenerative
      disease. Characterization of how inflammasomes may function in PD is a high
      priority because the majority of PD cases are sporadic, supporting the widely
      held belief that environmental exposure is a major factor in disease initiation
      and progression. Inflammasomes may represent a common mechanism that helps to
      explain the strong association between exposure and PD by mechanistically linking
      environmental toxicant-driven cellular stress with neuroinflammation and
      ultimately cell death.

PMID- 30203062
TI  - Life Expectancies With Depression by Age of Migration and Gender Among Older
      Mexican Americans.
AB  - Background and Objectives: Prior studies examining depression among older Mexican
      Americans suggest both women and immigrants are at higher risk of depressive
      symptomatology than males and U.S.-born Mexican Americans. We use data from the
      Hispanic Established Populations for the Epidemiologic Study of the Elderly to
      examine whether life expectancy with depression and without depression varies by
      nativity, age of migration, and gender. Research Design and Methods: Sullivan
      based life tables were used to estimate depression life expectancies among
      Mexican Americans aged 65 years and older residing in the Southwestern United
      States. Depression is based on the 20-item Center for Epidemiological Studies
      Depression scale (CES-D). The CES-D is a continuous scale (0-60) with higher
      values indicating worse mental health. We dichotomize depression as a score of 16
      or greater. Results: Immigrant women, particularly those who migrated in late
      life (after age 50) are at a significant disadvantage in the number of years
      after age 65 lived with depression and the ratio of years spent without
      depression relative to U.S.-born women. Among men, only late-life immigrants were
      disadvantaged in the number of years spent with depression. Early- and mid-life
      immigrant males did not differ from U.S.-born males. Discussion and Implications:
      Our results highlight the heterogeneity among older Mexican Americans in life
      expectancies with depression. These findings illustrate the importance of
      considering age of migration as a high-risk factor for depression among Mexican
      origin immigrants. Including this risk factor as a part of depression screening
      is a key step for timely interventions in preventing disability and comorbidities
      associated with untreated depression.

PMID- 30203065
TI  - Faster and more efficient swimming: Energy consumption of murine spermatozoa
      under sperm competition.
AB  - ATP supply is essential for sperm performance and increases in ATP content
      coevolve with enhanced sperm swimming velocity as a response to sperm competition
      in rodents. ATP content is the balance between production and consumption but,
      although ATP production has received much attention, little is known about ATP
      consumption. The rate of ATP consumption is crucial for the propagation of the
      flagellar wave, becoming a main determinant of the time and distance sperm could
      move before exhausting their reserves. A high yield in distance per unit of ATP
      consumed (efficiency) could provide advantages in sperm competition. We
      characterized sperm ATP consumption rate in a group of mouse species with
      different sperm competition levels to understand its impact on swimming velocity,
      duration, and yield of sperm ATP reserves. Interspecific comparisons revealed
      that sperm of species with higher sperm competition levels had high ATP
      consumption rates and faster swimming velocity. Moreover, sperm that consumed ATP
      at a faster rate swam more efficiently, since they were able to cover more
      distance per unit of ATP consumed. Our results suggest that by coupling the
      advantages of higher ATP turnover rates to increased efficiency of ATP
      expenditure, sperm would respond to increasingly competitive environments while
      maintaining a positive ATP balance.

PMID- 30203063
TI  - Using Experimental Models to Assess Effects of Bisphenol A (BPA) and Phthalates
      on the Placenta: Challenges and Perspectives.
AB  - The placenta is critical for all aspects of fetal development. Bisphenol A (BPA)
      and phthalates are endocrine disruptors with ubiquitous exposure in pregnant
      women-their effects on the placenta is an area of growing research interest.
      Therefore, our objectives were to (1) summarize research related to the effects
      BPA or phthalates on placental outcomes in animal and cell models, and (2)
      evaluate the challenges for using such models to study the impacts of these
      chemicals on placental endpoints. Overall, studies in cells and animal models
      suggest that BPA and phthalates impact placental hormones, some epigenetic
      endpoints, increase inflammation and oxidative stress, and decrease cell
      viability and nutrient transfer. However, few animal or cell studies have
      assessed these outcomes at concentrations relevant to humans. Furthermore, it is
      unclear whether effects of BPA/phthalates on the placenta in animal models
      mediate fetal outcomes, as most studies have dosed after the earliest stages of
      placental and fetal development. It is also unclear whether effects of these
      chemicals are sex-specific, as few studies have considered placental sex.
      Finally, while there is substantial evidence for effects of mono-(2-ethylhexyl)
      phthalate (the major metabolite of di-(2-ethylhexyl) phthalate), on placental
      endpoints in cells, little is currently known about effects of other phthalates
      to which pregnant women are exposed. Moving forward, these limitations will need
      to be addressed to help us understand the precise mechanisms of action of these
      chemicals within the placenta, and how these reported perturbations impact fetal
      health.

PMID- 30203066
TI  - New insights into the pelagic microorganisms involved in the methane cycle in the
      meromictic Lake Pavin through metagenomics.
AB  - Advances in metagenomics have given rise to the possibility of obtaining genome
      sequences from uncultured microorganisms, even for those poorly represented in
      microbial community, thereby providing important means to study their ecology and
      evolution. In this study, metagenomic sequencing was carried out at four sampling
      depths having different oxygen concentrations or environmental conditions in the
      water column of Lake Pavin. By analyzing the sequenced reads and matching the
      contigs to the proxy genomes of the closest cultivated relatives, we evaluated
      the metabolic potential of the dominant planktonic species involved in the
      methane cycle. We demonstrated that methane-producing communities were dominated
      by the genus Methanoregula while methane-consuming communities were dominated by
      the genus Methylobacter, thus confirming prior observations. Our work allowed the
      reconstruction of a draft of their core metabolic pathways. Although
      hydrogenotrophs, the presence of the genes required for acetate activation in the
      methanogen genome were also detected. Regarding methanotrophy, Methylobacter was
      present in the same areas as the non-methanotrophic, methylotrophic
      Methylotenera, which could suggest a relationship between these two groups.
      Furthermore, the presence of a large gene inventory for nitrogen metabolism
      (nitrate transport, denitrification, nitrite assimilation and nitrogen fixation,
      for instance) was detected in the Methylobacter genome.

PMID- 30203064
TI  - Mitochondrial Dynamics and Hypothalamic Regulation of Metabolism.
AB  - Mitochondria are cellular organelles that play an important role in bioenergetic
      processes. In the central nervous system, high energy-demanding neurons are
      critically dependent on mitochondria to fulfill their appropriate functions. The
      hypothalamus is a key brain area for maintaining glucose and energy homeostasis
      via the ability of hypothalamic neurons to sense, integrate, and respond to
      numerous metabolic signals. Mitochondrial function has emerged as an important
      component in the regulation of hypothalamic neurons controlling glucose and
      energy homeostasis. Although the underlying mechanisms are not fully understood,
      emerging evidence indicates that mitochondrial dysfunction in hypothalamic
      neurons may contribute to the development of various metabolic diseases,
      including obesity and type 2 diabetes mellitus (T2DM). In this review, we
      summarize recent studies demonstrating the link between mitochondria and
      hypothalamic neural control of glucose and energy homeostasis. Finally, this
      review provides an insight to understand how mitochondria in hypothalamic neurons
      may contribute to the development of metabolic disorders, such as T2DM and
      obesity.

PMID- 30203067
TI  - Study of 2009 H1N1 Pandemic Influenza Virus as a Possible Causative Agent of
      Diabetes.
AB  - Context: Recent studies have suggested that influenza A virus (IAV) might be
      involved in the etiology of diabetes. Objective and Methods: To address this
      question, we tested the ability of H1N1 pandemic IAV to infect, replicate, and
      damage human beta cells/pancreatic islets in vitro and induce pancreatic damage
      and/or glucose metabolism alterations in chemical and autoimmune models of beta
      cell damage in vivo. Moreover, we looked for direct and/or indirect evidence of
      correlation between IAV infection and autoimmunity/diabetes in humans. Results:
      Human H1N1 A/California/2009-derived viruses infected human pancreatic islets in
      vitro, inducing a proinflammatory response associated with substantial increases
      of CXCL9 and CXCL10 release. In vivo, infected mice showed a clear susceptibility
      to the virus, with its localization also found in extrapulmonary organs,
      including the pancreas. Infection was able to induce mild modifications of
      glycemia in C57B6 mice after chemical damage of islets but did not modulate the
      autoimmune damage of islets in NOD mice. One of 69 nasopharyngeal swabs collected
      from patients at the onset of type 1 diabetes yielded positive results for IAV.
      Pancreas sections from 17 organ donors available from the Network for Pancreatic
      Organ Donors With Diabetes showed the persistence of CXCL10-positive cells in
      islet autoimmunity-positive subjects; however, extremely rare cells stained for
      viral RNA and not preferentially in autoimmune subjects. Conclusion: Influenza
      H1N1 pdm strains are able to infect and replicate in mammalian pancreatic cells
      both in vitro and in vivo but did not cause any functional impairment consistent
      with diabetes.

PMID- 30203068
TI  - Transcriptional regulation of the ferric aerobactin receptor gene by a GntR-like
      repressor IutR in Vibrio furnissii.
AB  - We found that Vibrio furnissii can utilize aerobactin (AERO) as a
      xenosiderophore. A homology search of its genome revealed that this bacterium
      possesses genes encoding an AERO-mediated iron acquisition system similar to that
      of V. vulnificus. The system consists of the ABC transporter gene vatCDB, the
      GntR-type transcriptional repressor gene iutR, and the outer membrane receptor
      gene iutA. The functions of the vatCDB operon and iutA in V. furnissii were
      confirmed by the inability of the corresponding deletion mutants to utilize AERO.
      Reverse transcription-quantitative PCR revealed that iutA transcription under
      iron-limiting conditions was extensively activated by the addition of AERO to the
      growth medium; therefore, we focused on elucidating this phenomenon.
      Electrophoretic mobility shift and DNase I footprinting assays revealed that
      glutathione S-transferase-fused IutR (GST-IutR) bound directly to a specific
      palindromic sequence in the iutA promoter region. However, GST-IutR did not bind
      to this sequence when either AERO or ferric AERO was present in the assay
      mixture. These in vitro findings suggest that, under iron-limiting conditions,
      iutA transcription in V. furnissii is artfully regulated both by IutR, acting as
      a direct repressor of iutA, and by AERO, acting as an effector for IutR, leading
      to the derepression of iutA transcription.

PMID- 30203069
TI  - Mechanical prosthetic valve malfunction diagnosed by gated non-contrast computed
      tomography.

PMID- 30203070
TI  - Result of the 6-min walk test is an independent prognostic factor of surgically
      treated non-small-cell lung cancer.
AB  - OBJECTIVES: Pathological tumour, node and metastasis (TNM) stage remains the most
      significant prognostic factor of non-small-cell lung cancer (NSCLC). Meanwhile,
      age, gender, pulmonary function tests, the extent of surgical resection and the
      presence of concomitant diseases are commonly used to complete the prognostic
      profile of the patient with early stage of NSCLC. The aim of this study is to
      assess how the result of a 6-min walk test (6MWT) further assists in predicting
      the prognosis of NSCLC surgical candidates. METHODS: Six hundred and twenty-four
      patients who underwent surgical treatment for NSCLC between April 2009 and
      October 2011 were enrolled in this study. All patients were accepted for surgery
      on the basis of a standard evaluation protocol. Additionally, patients completed
      the 6MWT on the day before the surgery, and threshold values of the test were
      assessed based on both the Akaike information criterion and the coefficient of
      determination R2. Cox proportional hazards regression analysis was used to
      analyse the effect of important prognostic factors on the overall survival.
      RESULTS: Three hundred and ninety men and 234 women with a mean age of 64 years
      underwent radical surgical treatment for primary lung cancer. Five hundred and
      twenty-five lobectomies (84%), 77 pneumonectomies (12%) and 24 (4%) lesser
      resections were performed. Three hundred and thirty-one patients (53%) were
      treated for stage I NSCLC, 191 patients (31%) for stage II and 102 patients (16%)
      for stages IIIA-IV. A distance of 525 m in the 6MWT [hazard ratio (HR) = 0.57,
      95% confidence interval (CI) 0.41-0.78, P < 0.001] was the threshold value
      differentiating the patients' prognoses (P < 0.001). Using the Cox proportional
      hazards regression analysis, pathological TNM stage (IIA: HR = 1.87, 95% CI 1.95
      2.92, P = 0.006; IIB: HR = 2.03, 95% CI 1.23-3.37, P = 0.006; IIIA-IV: HR = 2.37,
      95% CI 1.49-3.75, P < 0.001), male gender (HR = 1.88, 95% CI 1.26-2.79, P =
      0.001), pneumonectomy (HR = 1.78, 95% CI 1.17-2.70, P < 0.001) and the results of
      the 6MWT (HR = 0.50, 95% CI 0.36-0.70, P < 0.001) were considered as independent
      predictive factors of overall survival. CONCLUSIONS: The result of a 6MWT is an
      independent and convenient prognostic factor of surgically treated non-small-cell
      lung cancer.

PMID- 30203072
TI  - The all-intracellular order Legionellales is unexpectedly diverse, globally
      distributed and lowly abundant.
AB  - Legionellales is an order of the Gammaproteobacteria, only composed of host
      adapted, intracellular bacteria, including the accidental human pathogens
      Legionella pneumophila and Coxiella burnetii. Although the diversity in terms of
      lifestyle is large across the order, only a few genera have been sequenced, owing
      to the difficulty to grow intracellular bacteria in pure culture. In particular,
      we know little about their global distribution and abundance.Here, we analyze
      16/18S rDNA amplicons both from tens of thousands of published studies and from
      two separate sampling campaigns in and around ponds and in a silver mine. We
      demonstrate that the diversity of the order is much larger than previously
      thought, with over 450 uncultured genera. We show that Legionellales are found in
      about half of the samples from freshwater, soil and marine environments, and
      quasi-ubiquitous in man-made environments. Their abundance is low, typically
      0.1%, with few samples up to 1%. Most Legionellales OTUs are globally
      distributed, while many do not belong to a previously identified species.This
      study sheds a new light on the ubiquity and diversity of one major group of host
      adapted bacteria. It also emphasizes the need to use metagenomics to better
      understand the role of host-adapted bacteria in all environments.

PMID- 30203073
TI  - Dosing vancomycin in the super obese: less is more.
AB  - Background: Vancomycin remains the mainstay of empirical therapy directed against
      MRSA. National guidelines recommend empirical dosing based on total body weight
      with trough-level therapeutic drug monitoring (TDM), which may not be optimal in
      obese and super obese patients. Furthermore, nomograms for empirical vancomycin
      dosing by estimated kidney function pre-date standardization of creatinine
      assays. Objectives: To determine an empirical vancomycin dosing strategy for
      obese and super obese adults that is consistent with the AUC monitoring paradigm.
      Methods: We conducted a population pharmacokinetic study using data obtained from
      routine peak and trough TDM of vancomycin in obese and super obese adults. An
      empirical dosing nomogram was developed using Monte Carlo simulation to identify
      vancomycin doses that optimize the probability of efficacy and minimize the
      probability of acute kidney injury based on AUC. Results: A total of 346 patients
      were included encompassing a wide range of body weight (69.6-293.6 kg) and BMI
      (30.1-85.7 kg/m2) values. In the final model, vancomycin clearance (CLV) was
      described using a linear combination of age, serum creatinine, sex and
      allometrically scaled body weight. Monte Carlo simulation demonstrated that
      maintenance doses >4500 mg/day were not required to achieve pharmacodynamic AUC
      targets in obese and super obese patients at clinically relevant values of CLV.
      Conclusions: Empirical vancomycin dosing informed by common clinical variables,
      including standardized creatinine, with subsequent individualization using AUC
      targeted TDM can optimize therapy in obese and super obese adults.

PMID- 30203074
TI  - One size does not fit all: towards personalized risk assessment in travel
      medicine.

PMID- 30203071
TI  - Successive Domain Rearrangements Underlie the Evolution of a Regulatory Module
      Controlled by a Small Interfering Peptide.
AB  - The establishment of new interactions between transcriptional regulators
      increases the regulatory diversity that drives phenotypic novelty. To understand
      how such interactions evolve, we have studied a regulatory module (DDR) composed
      by three MYB-like proteins: DIVARICATA (DIV), RADIALIS (RAD), and DIV-and-RAD
      Interacting Factor (DRIF). The DIV and DRIF proteins form a transcriptional
      complex that is disrupted in the presence of RAD, a small interfering peptide,
      due to the formation of RAD-DRIF dimers. This dynamic interaction result in a
      molecular switch mechanism responsible for the control of distinct developmental
      processes in plants. Here, we have determined how the DDR regulatory module was
      established by analyzing the origin and evolution of the DIV, DRIF, and RAD
      protein families and the evolutionary history of their interactions. We show that
      duplications of a pre-existing MYB domain originated the DIV and DRIF protein
      families in the ancestral lineage of green algae, and, later, the RAD family in
      seed plants. Intraspecies interactions between the MYB domains of DIV and DRIF
      proteins are detected in green algae, whereas the earliest evidence of an
      interaction between DRIF and RAD proteins occurs in the gymnosperms, coincident
      with the establishment of the RAD family. Therefore, the DDR module evolved in a
      stepwise progression with the DIV-DRIF transcription complex evolving prior to
      the antagonistic RAD-DRIF interaction that established the molecular switch
      mechanism. Our results suggest that the successive rearrangement and divergence
      of a single protein domain can be an effective evolutionary mechanism driving new
      protein interactions and the establishment of novel regulatory modules.

PMID- 30203075
TI  - Batf3-dependent intestinal dendritic cells play a critical role in the control of
      Cryptosporidium parvum infection.
AB  - Understanding the protective immune response to Cryptosporidium parvum infection
      is of critical importance to reduce the widespread impact caused by this disease
      in young individuals. Here, we analyzed the various subsets of CD103+ and CD103-
      intestinal dendritic cells (DCs) of wild-type and Batf3-/- neonatal mice at
      homoeostasis and investigated their role during infection. Neonatal Batf3-/- mice
      had a low CD103+/CD103- DC ratio, resulting in higher susceptibility to the acute
      phase of the infection and they could not cure the infection. Early during
      infection, CD103- DCs of Batf3-/- neonates had a lower ability to produce IL-12
      than their wild-type littermates and lower levels of IFNgamma mRNA were detected
      in the infected mucosa. Amplification of CD103+ DCs in Batf3-/- neonates prior to
      infectious challenge reduced their susceptibility to infection. CD103+ DCs thus
      outperform CD103- DCs in controlling C. parvum infections and represent a primary
      target of host-directed immunotherapies dedicated to neonates.

PMID- 30203076
TI  - Biomarkers of exposure among "dual users" of tobacco cigarettes and electronic
      cigarettes in Canada.
AB  - Introduction: "Dual use" refers to the concurrent use of tobacco cigarettes
      (smoking) and e-cigarettes (vaping). Although dual use is common among e
      cigarette users, there is little evidence regarding biomarkers of exposure among
      dual users and how these change under different conditions of product use.
      Methods: A non-blinded within-subjects cross-over experiment was conducted with
      adult daily dual users (n=48) in Ontario, Canada. Participants completed three
      consecutive seven-day periods in which the use of tobacco cigarettes and e
      cigarettes was experimentally manipulated, resulting in four study conditions:
      dual use, exclusive smoking, exclusive vaping, and no product use. Repeated
      measures models were used to examine changes in product use and biomarkers of
      exposure. Results: Compared to dual use, cotinine remained stable when
      participants exclusively smoked (p=0.524), but significantly decreased when they
      exclusively vaped (p=0.027), despite significant increases in e-cigarette
      consumption (p=0.001). Biomarkers of exposure to toxicants, including carbon
      monoxide (CO), 1-hydroxypyrene (1-HOP), and 4-(methylnitrosamino)-1-(3-pyridyl)-1
      butanol (NNAL) were significantly lower when participants exclusively vaped, as
      compared to when they engaged in dual use (CO: -41%, p<0.001; 1-HOP: -31%,
      p=0.025; NNAL: -30%, p=0.017). Similar findings were observed among participants
      abstaining from both products, as compared to dual use (CO: -26%, p<0.001; 1-HOP:
      -14% (ns); NNAL: -35%, p=0.016). In contrast, exposure biomarkers increased when
      participants exclusively smoked as compared to dual use (CO: +21%, p=0.029; 1
      HOP: +23%, p=0.048; NNAL: +8% (ns)). Conclusions: Although dual use may reduce
      exposure to tobacco smoke constituents to some extent, abstaining from smoking is
      the most effective way to reduce such exposure. Implications: Public health
      authorities should clearly communicate the relative risk of e-cigarettes and
      tobacco cigarettes to the general public, focusing on two salient points: 1) e
      cigarettes are not harmless, but they are less harmful than smoking tobacco
      cigarettes; and 2) using e-cigarettes while smoking may not necessarily reduce
      health risks; therefore, consumers should stop smoking completely to maximize
      potential health benefits.

PMID- 30203077
TI  - Loss of buoyancy control following a pneumonectomy: an update on Keeling syndrome
      with a biomechanics-based explanation.
AB  - Pneumonectomy although nowadays less prevalent, still remains a viable, practiced
      lung resection for the treatment of lung cancer and other lung pathologies.
      However, as radical surgery, it is associated with a number of postoperative
      complications and possible sequela. One such unusual complication discovered is
      the loss of buoyancy control and the ability to float and swim when compared
      preoperatively. We report on 2 post-pneumonectomy patients who experienced
      significant instability and loss of buoyancy when they attempted to resume
      recreational swimming and offer a possible biomechanics-based explanation for
      this.

PMID- 30203078
TI  - Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines
      on the Evaluation and Treatment of Patients With Thoracolumbar Spine Trauma:
      Prophylaxis and Treatment of Thromboembolic Events.
AB  - QUESTION 1: Does routine screening for deep venous thrombosis prevent pulmonary
      embolism (or venous thromboembolism (VTE)-associated morbidity and mortality) in
      patients with thoracic and lumbar fractures? RECOMMENDATION 1: There is
      insufficient evidence to recommend for or against routine screening for deep
      venous thrombosis in preventing pulmonary embolism (or VTE-associated morbidity
      and mortality) in patients with thoracic and lumbar fractures. Strength of
      Recommendation: Grade Insufficient. QUESTION 2: For patients with thoracic and
      lumbar fractures, is one regimen of VTE prophylaxis superior to others with
      respect to prevention of pulmonary embolism (or VTE-associated morbidity and
      mortality)? RECOMMENDATION 2: There is insufficient evidence to recommend a
      specific regimen of VTE prophylaxis to prevent pulmonary embolism (or VTE
      associated morbidity and mortality) in patients with thoracic and lumbar
      fractures. Strength of Recommendation: Grade Insufficient. QUESTION 3: Is there a
      specific treatment regimen for documented VTE that provides fewer complications
      than other treatments in patients with thoracic and lumbar fractures?
      RECOMMENDATION 3: There is insufficient evidence to recommend for or against a
      specific treatment regimen for documented VTE that would provide fewer
      complications than other treatments in patients with thoracic and lumbar
      fractures. Strength of Recommendation: Grade Insufficient. RECOMMENDATION 4:
      Based on published data from pooled (cervical and thoracolumbar) spinal cord
      injury populations, the use of thromboprophylaxis is recommended to reduce the
      risk of VTE events in patients with thoracic and lumbar fractures. Consensus
      Statement by the Workgroup The full version of the guideline can be reviewed at:
      https://www.cns.org/guideline-chapters/congress-neurological-surgeons-systematic
      review-evidence-based-guidelines/chapter_7.

PMID- 30203079
TI  - Discerning Depressive Symptoms in Patients with Obstructive Sleep Apnea: The
      Effect of Continuous Positive Airway Pressure Therapy on Hamilton Depression
      Rating Scale Symptoms.
AB  - Clinical Trial Name: Obstructive sleep apnoea and related symptoms study,
      www.australianclinicaltrials.gov.au, ACTRN12612001136897.

PMID- 30203080
TI  - Young deceased donor kidneys show a survival benefit over older donor kidneys in
      transplant recipients ages 20-50 years: a study by the ERA-EDTA Registry.
AB  - Background: Updated survival outcomes of young recipients receiving young or old
      deceased donor kidneys are required when considering accepting a deceased donor
      kidney. Methods: We examined outcomes in 6448 European kidney allografts donated
      from younger (>=20-<50 years) and older (>=50-<70 years) deceased donors when
      transplanted into very young (>=20-<35 years) or young (>=35-<50 years) adult
      recipients. Outcomes of first kidney transplantations during 2000-13 and followed
      up to 2015 were determined via competing risk, restricted mean survival and Cox
      regression methods. Results: The 10-year cumulative incidence of graft failure
      was lowest in very young {22.0% [95% confidence interval (95% CI) 19.1-24.9]} and
      young [15.3% (95% CI 13.7-16.9)] recipients of younger donor kidneys and highest
      in very young [36.7% (95% CI 31.9-41.5)] and young [29.2% (95% CI 25.1-33.2)]
      recipients of older donor kidneys. At the 10-year follow-up, younger donor
      kidneys had a 1 year (very young) or 9 months (young) longer mean graft survival
      time compared with older donor kidneys. Graft failure risk in younger donor
      kidneys was 45% [very young adjusted hazard ratio (aHR) 0.55 (95% CI 0.44-0.68)]
      and 40% [young aHR 0.60 (95% CI 0.53-0.67)] lower compared with older donor
      kidneys. A 1-year increase in donor age resulted in a 2% [very young aHR 1.02
      (95% CI 1.00-1.04)] or 1% [young aHR 1.01 (95% CI 1.00-1.01)] increase in the 10
      year risk of death. Conclusions: Younger donor kidneys show survival benefits
      over older donor kidneys in adult recipients ages 20-50 years. Updated survival
      outcomes from older deceased donors are necessary due to advances in
      transplantation medicine and the increasing role these donors play in organ
      transplantation.

PMID- 30203081
TI  - An exploratory study of the salivary IgA responses to one dose of a Norovirus VLP
      candidate vaccine in healthy adults.
AB  - As noroviruses are transmitted fecal-orally we investigated humoral and mucosal
      (salivary IgA) immune responses in a phase 2 trial of Takeda's bivalent norovirus
      virus-like particle (VLP) vaccine candidate in fifty healthy 18-49 year-olds. The
      vaccine had an acceptable tolerability profile, and induced rapid, robust humoral
      immune responses after one intramuscular dose of vaccine candidate. Seroresponses
      were evident 8 days after vaccination as Pan-Ig, IgA and histo-blood group
      antigen-blocking antibodies against both vaccine GI.1 and GII.4c genotypes.
      Salivary IgA levels were approximately 1000-fold lower than serum concentrations,
      and moderately or strongly correlated with the serum IgA titers at all time
      points.

PMID- 30203083
TI  - Giant Extra-Axial Cavernous Angioma of the Falx: Case Report.
AB  - BACKGROUND AND IMPORTANCE: Cavernous angiomas or cavernomas are vascular
      malformations usually located in the brain parenchyma. However, they rarely
      present as extra-axial lesions, attached to the dura, and may mimic meningiomas.
      Most reported cases concern the cavernous sinus region and other locations are
      very uncommon. CLINICAL PRESENTATION: A 61-yr-old female known for long-standing
      mental illness presented with progressive gait instability. Imaging studies
      revealed an extra-axial lesion in relation to the anterior part of the falx
      cerebri. An interhemispheric approach was used to remove the lesion. Pathological
      analysis revealed features compatible with an extra-axial cavernoma:
      structureless vascular channels lacking smooth muscle and elastic lamellae,
      without intervening brain parenchyma. CONCLUSION: Cavernous angiomas or
      cavernomas can present as extra-axial lesions. Although progressive growth can be
      observed, they should not be considered as tumoral lesions, because there is no
      cellular duplication. Unlike other locations, resection of anterior cranial fossa
      extra-axial cavernomas seems to be facilitated by minimal bleeding.

PMID- 30203084
TI  - Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines
      on the Evaluation and Treatment of Patients With Thoracolumbar Spine Trauma:
      Neurological Assessment.
AB  - QUESTION 1: Which neurological assessment tools have demonstrated internal
      reliability and validity in the management of patients with thoracic and lumbar
      fractures (ie, do these instruments provide consistent information between
      different care providers)? RECOMMENDATION 1: Numerous neurologic assessment
      scales (Functional Independence Measure, Sunnybrook Cord Injury Scale and Frankel
      Scale for Spinal Cord Injury) have demonstrated internal reliability and validity
      in the management of patients with thoracic and lumbar fractures. Unfortunately,
      other contemporaneous measurement scales (ie, American Spinal Cord Injury
      Association Impairment Scale) have not been specifically studied in patients with
      thoracic and lumbar fractures. Strength of Recommendation: Grade C. QUESTION 2:
      Are there any clinical findings (eg, presenting neurological grade/function) in
      patients with thoracic and lumbar fractures that can assist in predicting
      clinical outcomes? RECOMMENDATION 2: Entry American Spinal Injury Association
      Impairment Scale grade, sacral sensation, ankle spasticity, urethral and rectal
      sphincter function, and AbH motor function can be used to predict neurological
      function and outcome in patients with thoracic and lumbar fractures (Table I
      https://www.cns.org/guideline-chapters/congress-neurological-surgeons-systematic
      review-evidence-based-guidelines/chapter_4_table1). Strength of Recommendation:
      Grade B The full version of the guideline can be reviewed at:
      https://www.cns.org/guideline-chapters/congress-neurological-surgeons-systematic
      review-evidence-based-guidelines/chapter_4.

PMID- 30203082
TI  - Oxytocin reduces neural activation in response to infant faces in nulliparous
      young women.
AB  - Infant faces have distinctive features that together are described as baby
      schema, a configuration that facilitates caregiving motivation and behavior, and
      increases the perception of cuteness. In the current functional magnetic
      resonance imaging (fMRI) study, we investigated the effect of a within-subjects
      intranasal oxytocin administration (24 IU) and caregiving motivation on neural
      responses to infant faces of varying baby schema in 23 healthy nulliparous women.
      Overall, infant faces elicited activation in several brain regions involved in
      reward and salience processing, including the ventral tegmental area (VTA),
      putamen, amygdala, anterior cingulate cortex (ACC), and insula, and this
      activation was related to self-reported caregiving motivation. Critically,
      whereas we hypothesized enhanced neural caregiving-related responses after
      oxytocin administration, we observed reduced activation in the VTA, putamen and
      amygdala after oxytocin compared to placebo. In nulliparous women, oxytocin has
      been shown to reduce neural responses in the same regions in response to social
      stimuli using other paradigms. Oxytocin might affect neural activation toward
      social stimuli depending on elicited arousal and personal characteristics. The
      current study is the first to demonstrate this effect in response to infant faces
      and thereby adds to specify the role of oxytocin in human social information
      processing.

PMID- 30203085
TI  - Trajectory of Postconcussive Symptoms 12-Months Post-Deployment in Soldiers with
      and without Mild Traumatic Brain Injury - Warrior STRONG Study.
AB  - Postconcussive symptoms are believed to resolve in days or months in most
      instances for civilian injuries, though recent evidence suggests that recovery
      may be slower for injuries sustained during military deployment. The present
      study is based on a cohort of recently deployed soldiers from two US Army
      military bases (Fort Carson and Fort Bragg, followed from 2009-2015). Soldiers
      with and without a recent history of a deployment mild traumatic brain injury
      (mTBI) were evaluated within days of return and at 3, 6, and 12-months. Those
      with mTBI were more likely than non-mTBI to endorse one or more postconcussive
      symptoms at a severe and or very severe level (47% vs. 21% baseline; aRR=1.7 95%
      CI: 1.51,1.93 all-time points) and remained significant after adjusting for PTSD
      (aRR=1.34 95%CI: 1.41,1.82). Prevalence and relative risks (for three of most
      common baseline symptoms remained constant over time: sleep problems (RR=2.19),
      forgetfulness (RR=2.56), irritability (RR=2.73). The pattern was slightly
      different for headache, decreasing from RR=3.44 at baseline to RR=3.26 at 12
      months, due to increased prevalence of headache in those without mTBI. . The
      prevalence of clinically relevant postconcussive symptoms remained relatively
      constant over one year of follow-up, whether or not symptoms were associated with
      concussion. Service members with recent mTBI reported more symptoms than non-mTBI
      at all time-points.

PMID- 30203086
TI  - The potential of the transect method for early detection of welfare problems in
      broiler chickens.
AB  - The potential of the transect method was tested for early detection of welfare
      problems associated with bird age and genetic line, litter quality, and transect
      location. On-farm welfare impairment and its consequences on slaughter outcomes
      were evaluated to test the method's predictive ability. A total of 31 commercial
      Ross, Cobb, and mixed RC broiler flocks were evaluated at 3, 5, and 6 wk of age.
      Two observers evaluated 3 transects each, simultaneously and in the same house by
      detecting welfare indicators including lame, immobile, sick, small, dirty, tail
      wounds, other wounds (head and back wounds), featherless, terminally ill, and
      dead birds. Increasing lame, immobile, sick, and terminally ill birds according
      to bird age (P < 0.001) was detected. Higher incidences of small and sick birds
      were detected in C and RC (P < 0.001) as compared to R flocks, whereas more dead
      and tail wounded were observed in RC compared to R and C flocks at week 5 (P <
      0.001). Dirty incidence increased as litter quality deteriorated (P < 0.001). A
      higher incidence of immobile, small, sick, dirty, and dead was registered near
      house walls (P < 0.001). Differences across observers were detected for lame,
      immobile, and terminally ill birds (P < 0.001). For the observer by bird age
      interaction, differences were detected for dirty, tail wounds, and other wounds
      (P < 0.05). Pearson correlations between welfare indicators at week 3 and those
      at final weeks of age (P < 0.05) ranged between r values of -0.2 and 0.654 (P <
      0.05). Correlations between welfare indicators and slaughter outcomes showed a
      relationship between flock mortality and dead on arrival, footpad dermatitis, leg
      problems, and illness (P < 0.05). Litter quality positively correlated with
      downgrades (P < 0.001). This study showed the potential of transects to detect
      differences in welfare indicators according to factors that effects were
      previously reported. It demonstrated the transect potential for detecting and
      predicting the consequences of welfare impairment on slaughter outcomes. This
      would make the transect method a useful tool for notifying and rectifying welfare
      deterioration as early as at 3 wk of age.

PMID- 30203087
TI  - Isolation, characterization and germline chimera preparation of primordial germ
      cells from the Chinese Meiling chicken.
AB  - Primordial germ cells (PGCs) are precursors of germline cells that can generate
      sperm and eggs in adults, making them promising tools for transgenic animal
      preparation and germplasm preservation, especially in avians. In this study, we
      purified the PGCs from circulating embryonic blood of Chinese Meiling chickens
      using Nycodenz density centrifugation, and characterized them by alkaline
      phosphatase (AKP) staining, periodic acid-Schiff (PAS) staining and stage
      specific embryonic antigen-1 (SSEA-1) immunostaining and PGC-specific gene
      amplification. The purified PGCs were also labeled with PKH26 and transferred
      into donor chicken embryos at the Hamburger-Hamilton (HH) stage 14 to 16, and
      cells with red fluorescence were observed in the gonads of 8-d-old embryos. When
      using about 200 PGCs isolated from Chinese Meiling chickens, microinjection into
      the dorsal aortas of recipient chickens with white feathers at stage HH14 to 16
      resulted in germline chimeras that hatched and attained sexual maturity. The
      frequency of donor-derived yellow-feathered offspring from germline chimeric
      chickens was 12.6 +/- 2.6% after mating with the white-feathered chickens. These
      results demonstrate that we had successfully purified the PGCs from the Chinese
      Meiling chicken. These germline cells could be used to preserve Chinese Meiling
      chickens.

PMID- 30203088
TI  - Ethics and cloning.
AB  - Background: Scientists have cloned animals since the late 19th century, but the
      crucial step for ethics was the cloning of the first mammal by somatic cell
      nuclear transfer in 1997. This suggested that scientists could also clone, and
      possibly enhance, human beings. Sources of data: This survey examines ethical
      literature on cloning since the 1960s. Areas of agreement: The one ethical area
      of agreement in this issue is that we should not try to create new human beings
      by somatic cell nuclear transfer now. Areas of controversy: Ethicists disagree,
      however, on what justifies this norm. Some appeal to preference satisfaction and
      freedom from external constraints, others question this approach by more profound
      religious and moral considerations. Growing points: The discussion is currently
      not progressing, as the same arguments have been in use since the 1970s. Areas
      timely for developing research: Philosophers should prepare deeper analyses of
      the presuppositions of the ethical arguments used in the discussion before the
      issue surfaces again.

PMID- 30203089
TI  - Residual shunt diagnosed with 4D flow after reparation of post-infarct
      ventricular septal defect.

PMID- 30203091
TI  - The Causal Effect of Education on Tooth Loss: Evidence from UK Schooling Reforms.
AB  - Associations between education and oral health have frequently been reported, but
      until now there is no causal evidence. Exploiting exogenous variation in years of
      schooling due to 1947 and 1972 reforms in mandatory schooling in the UK; we
      examined the causal relationship between education and tooth loss in older age. A
      cross-sectional study was conducted using data from the English Longitudinal
      Study of Ageing (waves 3, 5 and 7). A Two-Stage Least Squares instrumental
      variables approach was employed. 5,667 respondents (average age = 67.8; 44.4%
      were men) were included in the analyses, of which 819 (14.5%) had no teeth. The
      schooling reforms increased years of education by an average of 0.624 years (95%
      CI: 0.412, 0.835). For respondents born within +/-6 years from the pivotal
      cohorts, a one-year increment of education causally reduced edentulism by 9.1
      (95% CI: 1.5, 16.8) % points. The effects were stronger for the 1947 reform than
      for the 1972 reform. Results were robust against broadening the cohort bandwidth
      and functional form of the cohort trend. The findings suggest oral health later
      in life improves in return to investments in school education.

PMID- 30203092
TI  - Effect of chronic melatonin supplementation during mid to late gestation on
      maternal uterine artery blood flow and subsequent development of male offspring
      in beef cattle.
AB  - The objective of the current study was to examine the effects of supplemental
      melatonin implants on uterine artery blood flow from mid to late gestation in
      beef cattle and subsequent development of their male offspring. Commercial beef
      heifers (n = 32) and cows (n = 25) were bred via artificial insemination and
      assigned to 1 of 2 groups supplemented with melatonin implants (MEL) or without
      (CON) at day 180, 210, and 240 of gestation. Uterine artery blood flow was
      determined using color Doppler ultrasonography. A subset of 12 crossbred heifers
      (n = 6 MEL; n = 6 CON) underwent Cesarean sections on day 243 +/- 2 of gestation
      to allow for placentome collection. Maternal and fetal serum were collected to
      analyze melatonin concentrations. The remaining cattle were allowed to calve and
      at weaning (195 +/- 2 d of age), bull calves (n = 15) were castrated and
      testicular tissue harvested for seminiferous tubule analysis. Heifer uterine
      artery blood flow was increased (P = 0.009) at day 240 of gestation in MEL
      compared with CON heifers. Cow uterine artery blood flow was increased (P =
      0.003) in MEL compared with CON cows irrespective of gestational day. Maternal
      and fetal concentrations of melatonin were increased (P < 0.05) in MEL compared
      with CON heifers. The percent of placentome capillary area per mm2 was decreased
      (P = 0.019) in MEL compared with CON heifers, while cotyledonary ANGPT1 mRNA
      tended to increase (P = 0.095) in MEL compared with CON heifers. At weaning, body
      weight of male offspring and their scrotal circumference were increased (P <
      0.05) in calves born to MEL compared with CON dams, while seminiferous tubule
      diameter and area were not different (P > 0.40) between treatments. In summary,
      melatonin supplementation increased uterine artery blood flow in mid to late
      gestating cattle, but this was not accompanied by an increase in fetal weight.
      Alterations in postnatal development of bulls, including increased body weight
      and scrotal circumference, warrants future investigations related to attainment
      of puberty and subsequent fertility of offspring born to melatonin supplemented
      dams.

PMID- 30203093
TI  - Bayesian modeling of dependence in brain connectivity data.
AB  - Brain connectivity studies often refer to brain areas as graph nodes and
      connections between nodes as edges, and aim to identify neuropsychiatric
      phenotype-related connectivity patterns. When performing group-level brain
      connectivity alternation analyses, it is critical to model the dependence
      structure between multivariate connectivity edges to achieve accurate and
      efficient estimates of model parameters. However, specifying and estimating
      dependencies between connectivity edges presents formidable challenges because
      (i) the dimensionality of parameters in the covariance matrix is high (of the
      order of the fourth power of the number of nodes); (ii) the covariance between a
      pair of edges involves four nodes with spatial location information; and (iii)
      the dependence structure between edges can be related to unknown network
      topological structures. Existing methods for large covariance/precision matrix
      regularization and spatial closeness-based dependence structure
      specification/estimation models may not fully address the complexity and
      challenges. We develop a new Bayesian nonparametric model that unifies
      information from brain network areas (nodes), connectivity (edges), and
      covariance between edges by constructing the function of covariance matrix based
      on the underlying network topological structure. We perform parameter estimation
      using an efficient Markov chain Monte Carlo algorithm. We apply our method to
      resting-state functional magnetic resonance imaging data from 60 subjects of a
      schizophrenia study and simulated data to demonstrate the performance of our
      method.

PMID- 30203095
TI  - High blood pressure in coronary artery disease: when to start treating and what
      to target?

PMID- 30203090
TI  - Role of plasmid plasticity and mobile genetic elements in the entomopathogen
      Bacillus thuringiensis serovar israelensis.
AB  - Bacillus thuringiensis is a well-known biopesticide that has been used for more
      than 80 years. This spore-forming bacterium belongs to the group of Bacillus
      cereus that also includes, among others, emetic and diarrheic pathotypes of B.
      cereus, the animal pathogen Bacillus anthracis and the psychrotolerant Bacillus
      weihenstephanensis. Bacillus thuringiensis is rather unique since it has adapted
      its lifestyle as an efficient pathogen of specific insect larvae. One of the
      peculiarities of B. thuringiensis strains is the extent of their extrachromosomal
      pool, with strains harbouring more than 10 distinct plasmid molecules. Among the
      numerous serovars of B. thuringiensis, 'israelensis' is certainly emblematic
      since its host spectrum is apparently restricted to dipteran insects like
      mosquitoes and black flies, vectors of human and animal diseases such as malaria,
      yellow fever, or river blindness. In this review, the putative role of the mobile
      gene pool of B. thuringiensis serovar israelensis in its pathogenicity and
      dedicated lifestyle is reviewed, with specific emphasis on the nature, diversity,
      and potential mobility of its constituents. Variations among the few related
      strains of B. thuringiensis serovar israelensis will also be reported and
      discussed in the scope of this specialised insect pathogen, whose lifestyle in
      the environment remains largely unknown.

PMID- 30203097
TI  - Expanding clinical spectrum of autosomal dominant pyrin-associated
      autoinflammatory disorder caused by the heterozygous MEFV p.Thr577Asn variant.

PMID- 30203098
TI  - Fermented corn-soybean meal elevated IGF1 levels in grower-finisher pigs.
AB  - Fermentation has attracted increasing attention in pig industry, because of low
      costs and numerous benefits on pig growth and health as well as environmental
      improvement, although the mechanisms remain largely unknown. In the present
      study, fermented corn-soybean meal significantly improved average daily gain and
      gain:food ratio (P < 0.05). Fermented feed (FF) significantly increased insulin
      like growth factor 1 (IGF1) transcription in liver (P < 0.05). Meanwhile,
      fermented meal significantly enhanced the binding of CCAAT/enhancer-binding
      protein beta (C/EBPbeta) to IGF1 promoter and C/EBPbeta expression in liver (both
      P < 0.05). FF tended to increase IGF1 proteins in liver and serum too (both 0.05
      < P < 0.10). Meanwhile, FF slightly but significantly increased hepatic and
      circulating triglyceride and total cholesterol levels, as well as serum ratio of
      high-density to low-density cholesterol (all P < 0.05). Our data indicated that
      FF could significantly augment the binding of C/EBPbeta to IGF1 promoter and
      promote hepatic IGF1 expression and production, thus boost pig growth.

PMID- 30203094
TI  - Converging Patterns of alpha-Synuclein Pathology in Multiple System Atrophy.
AB  - We aimed to determine patterns of alpha-synuclein (alpha-syn) pathology in
      multiple system atrophy (MSA) using 70-um-thick sections of 20 regions of the
      central nervous system of 37 cases with striato-nigral degeneration (SND) and 10
      cases with olivo-ponto-cerebellar atrophy (OPCA). In SND cases with the shortest
      disease duration (phase 1), alpha-syn pathology was observed in striatum,
      lentiform nucleus, substantia nigra, brainstem white matter tracts, cerebellar
      subcortical white matter as well as motor cortex, midfrontal cortex, and sensory
      cortex. SND with increasing duration of disease (phase 2) was characterized by
      involvement of spinal cord and thalamus, while phase 3 was characterized by
      involvement of hippocampus and amygdala. Cases with the longest disease duration
      (phase 4) showed involvement of the visual cortex. We observed an increasing
      overlap of alpha-syn pathology with increasing duration of disease between SND
      and OPCA, and noted increasingly similar regional distribution patterns of alpha
      syn pathology. The GBA variant, p.Thr408Met, was found to have an allele
      frequency of 6.94% in SND cases which was significantly higher compared with
      normal (0%) and other neurodegenerative disease pathologies (0.74%), suggesting
      that it is associated with MSA. Our findings indicate that SND and OPCA show
      distinct early foci of alpha-syn aggregations, but increasingly converge with
      longer disease duration to show overlapping patterns of alpha-syn pathology.

PMID- 30203096
TI  - Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines
      on the Evaluation and Treatment of Patients With Thoracolumbar Spine Trauma:
      Nonoperative Care.
AB  - BACKGROUND: Thoracic and lumbar burst fractures in neurologically intact patients
      are considered to be inherently stable, and responsive to nonsurgical management.
      There is a lack of consensus regarding the optimal conservative treatment
      modality. The question remains whether external bracing is necessary vs
      mobilization without a brace after these injuries. OBJECTIVE: To determine if the
      use of external bracing improves outcomes compared to no brace for neurologically
      intact patients with thoracic or lumbar burst fractures. METHODS: A systematic
      review of the literature was performed using the National Library of Medicine
      PubMed database and the Cochrane Library for studies relevant to thoracolumbar
      trauma. Clinical studies specifically comparing external bracing to no brace for
      neurologically intact patients with thoracic or lumbar burst fractures were
      selected for review. RESULTS: Three studies out of 1137 met inclusion criteria
      for review. One randomized controlled trial (level I) and an additional
      randomized controlled pilot study (level II) provided evidence that both external
      bracing and no brace equally improve pain and disability in neurologically intact
      patients with burst fractures. There was no difference in final clinical and
      radiographic outcomes between patients treated with an external brace vs no
      brace. One additional level IV retrospective study demonstrated equivalent
      clinical outcomes for external bracing vs no brace. CONCLUSION: This evidence
      based guideline provides a grade B recommendation that management either with or
      without an external brace is an option given equivalent improvement in outcomes
      for neurologically intact patients with thoracic and lumbar burst fractures. The
      decision to use an external brace is at the discretion of the treating physician,
      as bracing is not associated with increased adverse events compared to no brace.
      QUESTION: Does the use of external bracing improve outcomes in the nonoperative
      treatment of neurologically intact patients with thoracic and lumbar burst
      fractures? RECOMMENDATION: The decision to use an external brace is at the
      discretion of the treating physician, as the nonoperative management of
      neurologically intact patients with thoracic and lumbar burst fractures either
      with or without an external brace produces equivalent improvement in outcomes.
      Bracing is not associated with increased adverse events compared to not bracing.
      Strength of Recommendation: Grade B The full version of the guideline can be
      reviewed at: https://www.cns.org/guideline-chapters/congress-neurological
      surgeons-systematic-review-evidence-based-guidelines/chapter_8.

PMID- 30203099
TI  - Claudin18.2-Specific Chimeric Antigen Receptor Engineered T Cells for the
      Treatment of Gastric Cancer.
AB  - Background: Claudin18.2 (CLDN18.2), a gastric-specific membrane protein, has been
      regarded as a potential therapeutic target for gastric cancer and other cancer
      types. The aim of our study was to elucidate whether chimeric antigen receptor T
      (CAR T) cells redirected to CLDN18.2 have the potential to be used in the
      treatment of this deadly disease. Methods: CLDN18.2-specific humanized antibodies
      were developed using hybridoma and humanization technology. CLDN18.2-specific CAR
      T cells were prepared by lentiviral vector transduction. In vitro antitumor
      activities and cytokine production of the CAR T cells to gastric cancer cell
      lines were examined by cytotoxicity and ELISA assay. In vivo antitumor activities
      of CAR T cells were evaluated in mice bearing gastric cancer cell line and
      patient-derived tumor xenograft (PDX) models (n >= 6 mice per group). All
      statistical tests were two-sided. Results: Humanized CLDN18.2-specific hu8E5 and
      hu8E5-2I single-chain fragment variables (scFv) were successfully developed.
      CLDN18.2-specific CAR T cells were developed using hu8E5 or hu8E5-2I scFv as
      targeting moieties. Both hu8E5-28Z and hu8E5-2I-28Z CAR T cells comprising the
      CD28 costimulatory domain potently suppressed tumor growth in a cancer cell line
      xenograft mouse model (mean [SD] tumor volume: hu8E5-28Z = 118.0 [108.6] mm3 and
      hu8E5-2I-28Z group = 75.5 [118.7] mm3 vs untransduced T cell group = 731.8
      [206.3] mm3 at day 29 after tumor inoculation, P < .001). Partial or complete
      tumor elimination was observed in CLDN18.2-positive gastric cancer PDX models
      treated with the hu8E5-2I-28Z CAR T cells (P < .001), which persist well in vivo
      and infiltrate efficiently into the tumor tissues. Although the CLDN18.2 CAR T
      cells could lyse target cells expressing murine CLDN18.2 (mCLDN18.2), no obvious
      deleterious effect on the normal organs including the gastric tissues was
      observed in the mice. Conclusions: CLDN18.2-specific CAR T cells could be a
      promising treatment strategy for gastric cancer and potentially other CLDN18.2
      positive tumors.

PMID- 30203100
TI  - Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines
      on the Evaluation and Treatment of Patients with Thoracolumbar Spine Trauma:
      Surgical Approaches.
AB  - QUESTION: Does the choice of surgical approach (anterior, posterior, or combined
      anterior-posterior) improve clinical outcomes in patients with thoracic and
      lumbar fractures? RECOMMENDATIONS: In the surgical treatment of patients with
      thoracolumbar burst fractures, physicians may use an anterior, posterior, or a
      combined approach as the selection of approach does not appear to impact clinical
      or neurological outcomes. Strength of Recommendation: Grade B With regard to
      radiologic outcomes in the surgical treatment of patients with thoracolumbar
      fractures, physicians may utilize an anterior, posterior, or combined approach
      because there is conflicting evidence in the comparison among approaches.
      Strength of Recommendation: Grade Insufficient With regard to complications in
      the surgical treatment of patients with thoracolumbar fractures, physicians may
      use an anterior, posterior, or combined approach because there is conflicting
      evidence in the comparison among approaches. Strength of Recommendation: Grade
      Insufficient The full version of the guideline can be reviewed at:
      https://www.cns.org/guideline-chapters/congress-neurological-surgeons-systematic
      review-evidence-based-guidelines/chapter_11.

PMID- 30203101
TI  - Triamcinolone acetonide extended-release in patients with osteoarthritis and type
      2 diabetes: a randomized, phase 2 study.
AB  - Objective: Approximately 30% of patients with type 2 diabetes mellitus have knee
      osteoarthritis. IA corticosteroids used to manage osteoarthritis pain can elevate
      blood glucose in these patients. We compared blood glucose levels following intra
      articular injection of triamcinolone acetonide extended-release (TA-ER), an
      extended-release, microsphere-based triamcinolone acetonide formulation, vs
      standard triamcinolone acetonide crystalline suspension (TAcs) in patients with
      knee osteoarthritis and comorbid type 2 diabetes. Methods: In this double-blind,
      randomized, parallel-group, phase 2 study (NCT02762370), 33 patients with knee
      osteoarthritis (American College of Rheumatology criteria) and type 2 diabetes
      mellitus (HbA1c 6.5-9.0% [48-75 mmol/mol]; 1-2 oral hypoglycaemic agents) were
      treated with intra-articular TA-ER (32 mg n = 18) or TAcs 40 mg (n = 15).
      Continuous glucose monitoring-measured glucose (CGMG) was assessed from 1 week
      pre-injection through 2 weeks postinjection. Endpoints included change in average
      daily CGMG from baseline (days -3 to -1) to days 1-3 postinjection (CGMGdays1-3)
      (primary) and percent time average hourly CGMG levels remained in prespecified
      glycaemic ranges. Results: The change CGMGdays1-3 was significantly lower
      following TA-ER vs TAcs (14.7 vs 33.9 mg/dl, least-squares-mean-difference [95%
      CI]: -19.2 [-38.0, -0.4]; P = 0.0452). The percentage of time over days 1-3 that
      CGMG was in the target glycaemic range (70-180 mg/dl) was numerically greater for
      TA-ER (63.3%) vs TAcs (49.7%), and that CGMG was >180 mg/dl was lower for TA-ER
      (34.5%) vs TAcs (49.9%). Non-glycaemic adverse events were mild and comparable
      between groups. Conclusion: TA-ER may enable intra-articular corticosteroid
      treatment with minimal blood glucose disruption in patients with knee
      osteoarthritis and type 2 diabetes mellitus. Trial registration:
      ClinicalTrials.gov, https://clinicaltrials.gov, NCT02762370.

PMID- 30203102
TI  - Dispersive solid-phase extraction based on MoS2/carbon dot composite combined
      with HPLC to determine brominated flame retardants in water.
AB  - The method based on the dispersive solid-phase extraction (DSPE) by novel
      molybdenum disulfide modified with carbon dot (MoS2/CD) composite combined with
      high-performance liquid chromatography (HPLC) was developed for the determination
      of three brominated flame retardants (BFRs), including tetrabromobisphenol A
      (TBBPA), tetrabromobisphenol A bisallylether (TBBPA-BAE), and tetrabromobisphenol
      A bis(2,3-dibromopropyl ether) (TBBPA-BDBPE). Owing to the stacked planar
      structure and large surface area of MoS2, a large number of CDs can be easily
      loaded on the surface of MoS2. Benefiting from good dispersing capability of
      MoS2, similar density with analytes, and hydrogen bonds between CDs and the
      target analytes, the CDs on the surface of MoS2 as sorbent for the DSPE procedure
      exhibited good extraction performance. Under optimal conditions, application of
      the developed method to analyze BFRs from real water samples resulted in good
      recovery values ranging from 80 to 91% with relative standard deviation (RSD)
      values lower than 6.5%. Limits of detection (LODs) were in the range of 0.01-0.06
      MUg/L. The result above showed that the method has potential for the extraction
      and detection of trace-level BFRs from real water sample. Graphical abstract
      Owing to the stacked planar structure and large surface area of MoS2, a large
      number of CDs can be easily loaded on the surface of MoS2. Benefiting from good
      dispersing capability of MoS2, similar density with analytes, and hydrogen bonds
      between CDs and the target analytes, the prepared MoS2/CD composites as sorbent
      for the DSPE procedure exhibited good extraction performance. Accordingly, the
      extraction yield of BFRs was improved, which was favorable to its accurate
      determination in sample.

PMID- 30203103
TI  - Incidence and risk of ptosis following ocular surgery: a systematic review and
      meta-analysis.
AB  - OBJECTIVE: We conducted a systematic review and meta-analysis to evaluate the
      incidence and risk factors of ptosis following ocular surgery. METHODS: PubMed,
      Embase, and Cochrane Library were searched for articles that assessed the
      incidence or risk factors of ptosis following ocular surgery up to October 2017.
      We used a fixed effects model to calculate a pooled estimate of incidence, with
      subgroup analyses to evaluate the effect of different variables. The relative
      risks (RRs) or odds ratios (ORs) and 95% confidence intervals (CIs) for all
      available factors were calculated using the fixed effects models. RESULTS: A
      total of 16 studies on 2856 eyes were analyzed, including 3 randomized controlled
      trials (RCTs) and 13 cohort studies. The overall incidence of ptosis following
      ocular surgery was 11.4% (95% CI 10.1-12.8%). Subgroup analyses showed that the
      region and the surgery type were significantly associated with the incidence of
      postoperative ptosis. Men were less likely to get postoperative ptosis than women
      (OR 0.62; 95% CI 0.43-0.89). However, age (OR 0.77; 95% CI 0.48-1.23), side (OR
      1.37; 95% CI 0.84-2.25), type of anesthesia (OR 0.57; 95% CI 0.16-2.05), prior
      surgery (OR 1.09; 95% CI 0.64-1.83), bridle suture (OR 2.04; 95% CI 0.94-4.42),
      or combined surgery (OR 0.95; 95% CI 0.58-1.57) did not significantly change the
      risk of ptosis following ocular surgery. CONCLUSION: More than one in ten
      patients who undergo ocular surgery will develop ptosis. Different regions and
      surgery types may influence the occurrence of this abnormality. Female gender is
      a risk factor for development of postoperative ptosis.

PMID- 30203104
TI  - Improved analysis of foveal avascular zone area with optical coherence tomography
      angiography.
AB  - PURPOSE: To investigate the relationship between the foveal avascular zone (FAZ)
      and the inner nuclear layer (INL)-free zone in the center of the fovea in order
      to provide an improved approach to evaluation of the FAZ area with optical
      coherence tomography angiography (OCTA). METHODS: Thirty-six healthy individuals
      (36 eyes) and 15 age-matched patients (15 eyes) with nonproliferative diabetic
      retinopathy (nPDR) were included in this study. The FAZ, as well as INL-free
      zone, was measured on OCTA images. The FAZ area, INL-free zone area, and the
      ratio of the INL-free zone area to the FAZ area were compared between healthy
      subjects and nPDR patients. RESULTS: The mean FAZ area in healthy subjects and
      nPDR patients was 0.33 +/- 0.1 mm2 and 0.41 +/- 0.19 mm2 (p < 0.05),
      respectively. The mean INL-free zone area in healthy subjects and nPDR patients
      was 0.33 +/- 0.07 mm2 and 0.25 +/- 0.09 mm2 (p > 0.05), respectively. The INL
      free zone area to the FAZ area ratio in healthy subjects and nPDR patients was
      1.08 +/- 0.25 and 0.56 +/- 0.18 (p < 0.001), respectively. Receiver operating
      characteristic analysis showed that the INL-free zone area to the FAZ area ratio
      had a higher area under curve (0.94; 80.0% sensitivity and 97.2% specificity)
      compared to the FAZ area (0.61; 40.0% sensitivity and 94.4% specificity) for
      differentiating nPDR from healthy eyes. CONCLUSION: This study showed that
      analysis of the FAZ based on the ratio of the INL-free zone area to the FAZ area
      has better accuracy compared to the conventional FAZ area measurement in
      differentiating eyes with mild to moderate nPDR without any structural
      abnormalities in the fovea from healthy eyes.

PMID- 30203105
TI  - Assessment of ocular microcirculation in patients with end-stage kidney disease.
AB  - PURPOSE: To determine the impact that end-stage kidney disease (ESKD) has on
      ocular microcirculation in the optic nerve head (ONH) and choroid area shown by
      laser speckle flowgraphy (LSFG). METHODS: We studied 24 consecutive Japanese
      patients with ESKD who visited the department of Nephrology at our hospital and
      55 age- and gender-matched subjects who had undergone polysomnography. The mean
      blur rates (MBRs) in vessels (MBR-Vessel), in the tissue (MBR-Tissue), throughout
      the ONH (MBR-All), and throughout the choroid (MBR-Choroid) were analyzed. We
      divided the MBR-Tissue into four sections (superior, temporal, inferior, and
      nasal). The results of systemic and ocular parameters were compared between the
      ESKD patients and control subjects. We performed single and multiple regression
      analyses to determine the MBR section(s) that correlated most strongly with serum
      creatinine and the estimated glomerular filtration rate (eGFR) and to identify
      the independent factors for selected MBR sections in the ESKD patients. RESULTS:
      All sections of the ONH in the ESKD patients were significantly lower than those
      in the control subjects. MBR-Choroid was not significantly different between the
      control and ESKD groups. The single regression analyses revealed that MBR-Tissue
      had the strongest correlations with creatinine and the eGFR. The multiple
      regression analyses revealed hematocrit, creatinine, and eGFR as factors
      independently contributing to the MBR-Tissue. The inferior section of MBR-Tissue
      was most strongly correlated with creatinine and the eGFR. CONCLUSION: The MBRs
      in the ONH of the ESKD patients decrease compared with control subjects and the
      inferior section of MBR-Tissue is correlated with serum creatinine and eGFR.

PMID- 30203106
TI  - Analysis of the ars gene cluster from highly arsenic-resistant Burkholderia
      xenovorans LB400.
AB  - The Burkholderia xenovorans LB400 multireplicon genome displays a relatively high
      proportion of redundant genes, including several genes predicted to be related to
      arsenic resistance. These comprise an ars gene cluster, composed of the arsR3,
      acr3, arsC1 and arsH genes, as well as two arsB, arsC2, and seven individual arsR
      genes. The objective of this work was to elucidate the involvement of the ars
      gene cluster in arsenic resistance by the LB400 strain. Susceptibility tests
      showed that B. xenovorans LB400 is highly resistant to arsenate and arsenite.
      Arsenic resistance was induced by prior exposure of LB400 to arsenate or
      arsenite. reverse transcription-polymerase chain reaction assays using total RNA
      from LB400 showed arsenite-induced transcription of the arsR3 gene, suggesting
      that the ars gene cluster constitutes an arsenite-responsive operon. Transfer of
      cloned LB400 ars genes to heterologous Escherichia coli or Pseudomonas aeruginosa
      strains demonstrated that the ArsR3 transcriptional repressor, ArsC1 arsenate
      reductase, and the Acr3 arsenite efflux pump encoded in the LB400 ars gene
      cluster, are all associated to the arsenic resistance phenotype of this strain.
      The ars gene cluster from Burkholderia xenovorans LB400 is responsible for the
      inducible arsenic-resistance phenotype of the bacterium.

PMID- 30203107
TI  - Electric- Field-Modified In Situ Precise Deposition of Electrospun Medical Glue
      Fibers on the Liver for Rapid Hemostasis.
AB  - Precise deposition of nanofibers is still an important issue in the applications
      of electrospinning (e-spinning), especially in rapid hemostasis of organs such as
      the liver, lung, and kidney. In this study, we propose an electric field-modified
      e-spinning technique with a metal cone attached to the spinning nozzle to realize
      controllable precise deposition of fibers. The deposition range of the e-spun
      fibers is tunable by changing the size of the metal cone, and the mechanism is
      attributed the focused electric field verified by theoretical simulations. This
      electric field-modified e-spinning method was further used to in situ precisely
      deposit medical glue N-octyl-2-cyanoacrylate (NOCA) fibers onto the resection
      site of rat liver to realize rapid hemostasis within 10 s. Postoperative
      pathological results indicate that less inflammatory response and tissue adhesion
      are observed in this electric field-modified e-spinning group compared with that
      of traditional airflow-assisted group. This technique combined with our designed
      handheld e-spinning device could be used in emergency medical treatment, clinics,
      field survival, and home care for its portability and precise deposition
      characteristics.

PMID- 30203108
TI  - Cross-talk between lung cancer and bones results in neutrophils that promote
      tumor progression.
AB  - Lung cancer is the leading cause of cancer mortality around the world. The lack
      of detailed understanding of the cellular and molecular mechanisms participating
      in the lung tumor progression restrains the development of efficient treatments.
      Recently, by using state-of-the-art technologies, including in vivo sophisticated
      Cre/loxP technologies in combination with lung tumor models, it was revealed that
      osteoblasts activate neutrophils that promote tumor growth in the lung.
      Strikingly, genetic ablation of osteoblasts abolished lung tumor progression via
      interruption of SiglecFhigh-expressing neutrophils supply to the tumor
      microenvironment. Interestingly, SiglecFhigh neutrophil signature was associated
      with worse lung adenocarcinoma patients outcome. This study identifies novel
      cellular targets for lung cancer treatment. Here, we summarize and evaluate
      recent advances in our understanding of lung tumor microenvironment.

PMID- 30203109
TI  - Cancers of the eye.
AB  - Ocular cancers are unique among the diseases of the eye, threatening both vision
      and life. In most cases, the diagnosis can be made utilizing a careful clinical
      history and specialized ocular examination. Eye cancer diagnosis relies heavily
      on imaging techniques such as high-frequency ultrasound, fluorescein angiography,
      anterior and posterior segment optical coherence tomography, computed tomography
      (CT), and magnetic resonance imaging (MRI). Once the diagnosis is established,
      treatment decisions depend on the tumor's location, size, local extension,
      patterns of growth, and secondary complications. Treatment options include
      observation, local resection, chemotherapy (topical, intravenous, intra-arterial,
      or intravitreal), and radiation (ophthalmic plaque or external beam). Enucleation
      or exenteration is only employed if these eye- and vision-sparing treatments are
      not possible. The core of this comprehensive review is a consecutive series of
      the most common ocular tumor of each structure of the eye, anterior to posterior,
      including basal cell carcinoma of the eyelid, squamous conjunctival neoplasia,
      choroidal melanoma, retinoblastoma, ocular adnexal lymphoma, and metastatic
      orbital tumors.

PMID- 30203111
TI  - Treatment outcomes of radiotherapy for primary spinal cord glioma.
AB  - PURPOSE: Spinal cord gliomas are rare, and there is no consensus on the optimal
      radiotherapy (RT) regimen. Herein, we investigated therapeutic outcomes in spinal
      cord gliomas to obtain clues for the optimal RT regimen. METHODS: We assessed 45
      patients who received RT for primary spinal cord non-ependymoma gliomas between
      2005 and 2017: 37 (82%) received postoperative RT, 6 (13%) underwent definitive
      RT without surgery, and 2 (5%) received salvage RT for recurrent tumors.
      Craniospinal irradiation (CSI; median, 40 Gy) was administered in 4 patients with
      seeding at diagnosis; all other patients received local RT only (median, 50.4
      Gy). RESULTS: In all 23 failures occurred (20 in patients without initial seeding
      +3 in patients with initial seeding and CSI; median follow-up, 33 months). The 2
      year overall survival and progression-free survival rates were 74 and 54%,
      respectively. Overall, 13 (32%) new seeding events outside the local RT field
      developed either first or subsequently. Tumor grade was significantly associated
      with survival endpoints (p = 0.009, 0.028) and overall seeding rates (p = 0.042).
      In grade II tumors, seeding developed in 23%, with a dismal prognosis (median, 10
      months after RT). In grade III tumors, seeding developed in 45% with diverse
      prognosis. In grade IV tumors, seeding developed in 45%. The survival of patients
      with newly developed seeding was significantly worse than the others (2-year 50%,
      p < 0.001). CONCLUSION: To encompass a considerable rate of progressive disease
      seeding, aggressive treatment such as pre-emptive application of CSI needs to be
      considered for high-grade spinal cord gliomas with adverse features. Prophylactic
      CSI could be an option for survival prolongation and requires prospective
      validation.

PMID- 30203110
TI  - CT-guided interstitial HDR-brachytherapy for recurrent glioblastoma multiforme: a
      20-year single-institute experience.
AB  - PURPOSE: To report our results of computed tomography-guided interstitial high
      dose-rate (HDR) brachytherapy (BRT) in the treatment of patients with recurrent
      inoperable glioblastoma multiforme (GBM). PATIENTS AND METHODS: Between 1995 and
      2014, 135 patients were treated with interstitial HDR BRT for inoperable
      recurrent GBM located within previously irradiated volumes. Patient's median age
      was 57.1 years (14-82 years). All patients were pretreated with surgery,
      postoperative external beam radiation therapy (EBRT) and systemic chemotherapy
      (ChT). The median recurrent tumor volume was 42 cm3 (2-207 cm3). The prescribed
      HDR dose was median 40 Gy (30-50 Gy) delivered in twice-daily fractions of 5.0 Gy
      over consecutive days. No repeat surgery or ChT was administered in conjunction
      with BRT. Survival from BRT, progression-free survival (PFS), toxicity as well as
      the impact of several prognostic factors were evaluated. RESULTS: At a median
      follow-up of 9.2 months, the median overall survival following BRT and the median
      PFS were 9.2 and 4.6 months, respectively. Of the prognostic variables evaluated
      in univariate analysis, extent of surgery at initial diagnosis, tumor volume at
      recurrence, as well as time from EBRT to BRT reached statistical significance,
      retained also in multivariate analysis. Eight patients (5.9%) developed treatment
      associated complications including intracerebral bleeding in 4 patients (2.9%),
      symptomatic focal radionecrosis in 3 patients (2.2%), and severe convulsion in 1
      patient (0.7%). CONCLUSIONS: For patients with recurrent GBM, interstitial HDR
      BRT is an effective re-irradiation method for even larger tumors providing
      palliation without excessive toxicity.

PMID- 30203112
TI  - Radiosurgery of vestibular schwannoma: prognostic factors for hearing outcome
      using 3D-constructive interference in steady state (3D-CISS).
AB  - PURPOSE: Stereotactic radiosurgery (SRS) is an effective treatment for vestibular
      schwannoma (VS). Three-dimensional (3D) constructive interference in steady state
      (CISS) is the preferred magnetic resonance imaging (MRI) sequence for evaluating
      signal changes in the inner ear endolymph. Previous studies demonstrated a
      correlation between pretreatment cochlear signal intensity in 3D-CISS and
      posttherapeutic hearing outcomes. The purpose of our study was to compare 3D-CISS
      sequences before and after primary SRS of unilateral VSs to evaluate the effect
      of radiosurgery on the 3D-CISS signal intensities of cochlea and
      sacculus/utriculus. METHODS: We retrospectively reviewed 47 patients with
      unilateral VS treated with SRS. The neuroradiological MRI datasets were analysed
      to evaluate the signal intensity of the inner ear structure, tumour size, Koos
      grade, tumour volume, and infiltration of the cochlear aperture before therapy
      and at follow-up. The differences in these signal intensities before SRS and at
      follow-up were correlated with clinical symptoms, cochlear radiation dose, tumour
      volume and infiltration of the cochlear aperture. RESULTS: No differences were
      found between signal intensities in cochlea and utriculus/sacculus before and
      after SRS and no correlation with clinical symptoms, cochlear radiation dose,
      tumour volume, Koos grade or infiltration of the cochlear aperture (all p >
      0.05). CONCLUSION: Our study supports the theory of a complex interaction causing
      alteration of the endolymph protein concentration and not a direct dependency on
      the SRS. Use of modern dosing schemes will have a positive impact on clinical
      outcome with preservation of hearing in patients with VS.

PMID- 30203113
TI  - Long-term effects of tacrolimus for maintenance therapy of lupus nephritis: a 5
      year retrospective study at a single center.
AB  - Previously, we reported the short-term effects of tacrolimus in treating lupus
      nephritis (LN); however, long-term data are lacking. We conducted a retrospective
      study of 26 adult patients with LN. Tacrolimus was initiated at a dose of 3
      mg/day after induction therapy. We retrospectively collected data on renal
      response; modified lupus nephritis disease activity index (m-LNDAI), including
      hematuria, proteinuria, complement 3, anti-double-stranded DNA antibody, and
      estimated glomerular filtration rate (eGFR); and prednisolone (PSL) dose. Three
      patients discontinued tacrolimus treatment because of related complications,
      including acute myeloblastic leukemia, tremor, or a general personal choice or a
      desire to become pregnant. We analyzed data from 23 patients who were treated
      with tacrolimus over a 5-year period. The mean urinary protein/creatinine ratio
      decreased from a baseline of 0.24 (min 0.00-max 4.20) to 0.00 (0.00-7.05) at 5
      years (p = 0.0134), while eGFR levels remained unchanged throughout the 5 years.
      The mean m-LNDAI decreased from a baseline of 3.00 (0.00-12.0) to 2.00 (0.00
      4.00) at 5 years (p = 0.0074). The mean PSL dose decreased from a baseline of
      0.33 (0.00-0.75) mg/kg/day to 0.15 (0.15-0.33) at 5 years (p = 0.001). Our
      results suggest that tacrolimus is potentially effective for treating LN and that
      the current dosage was generally well tolerated for long-term maintenance
      treatment in our patients with LN.

PMID- 30203114
TI  - Application of CRISPR/Cas9 technologies combined with iPSCs in the study and
      treatment of retinal degenerative diseases.
AB  - Retinal degeneration diseases, such as age-related macular degeneration and
      retinitis pigmentosa, affect millions of people worldwide and are major causes of
      irreversible blindness. Effective treatments for retinal degeneration, including
      drug therapy, gene augmentation or transplantation approaches, have been widely
      investigated. Nevertheless, more research should be dedicated to therapeutic
      methods to improve future clinical treatments. Recently, with the rapid
      development of genome-editing technology, gene therapy has become a potentially
      effective treatment for retinal degeneration diseases. A clustered regularly
      interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9)
      system has been developed as a powerful genome-editing tool in ophthalmic
      studies. The CRISPR/Cas9 system has been widely applied in basic research to
      develop animal models and gene therapies in vivo. With the ability to self-renew
      and the potential to differentiate into different types of cells, induced
      pluripotent stem cells (iPSCs) have already been used as a promising tool for
      understanding disease pathophysiology and evaluating the effect of drug and gene
      therapeutics. iPSCs are also a cell source for autologous transplantation. In
      this review, we compared genome-editing strategies and highlighted the advantages
      and concerns of the CRISPR/Cas9 system. Moreover, the latest progress and
      applications of the CRISPR/Cas9 system and its combination with iPSCs for the
      treatment of retinal degenerative diseases are summarized.

PMID- 30203118
TI  - Adolescent Emotion Network Dynamics in Daily Life and Implications for
      Depression.
AB  - Emotion network density describes the degree of interdependence among emotion
      states across time. Higher density is theorized to reflect rigidity in emotion
      functioning and has been associated with depression in adult samples. This paper
      extended research on emotion networks to adolescents and examined associations
      between emotion network density and: 1) emotion regulation and 2) symptoms of
      depression. Data from a daily diary study (t = 21 days) of adolescents (N = 151;
      61.59% female; mean age = 14.60 years) were used to construct emotion network
      density scores. Emotion regulation was measured using The Difficulties in Emotion
      Regulation Scale Short Form (DERS-SF). Depression was measured using the Revised
      Child Anxiety and Depression Scale-Short Version (RCADS-SV). Associations between
      emotion network density and DERS-SF were examined through Pearson correlations.
      Multiple regression analyses examined associations between emotion network
      density and depression. Emotion network density was not associated with the DERS
      SF. Follow-up analyses showed that it was positively associated with non
      acceptance of emotions (a subscale of the DERS-SF). Emotion network density was
      positively associated with RCADS-SV depression. Non-acceptance of emotions may
      encourage the spread of emotion across time and states given that a feature of
      non-acceptance is to have secondary emotional responses to one's emotions.
      Emotion networks that are self-predictive may be a risk factor for adolescent
      depression.

PMID- 30203115
TI  - Real-World Variability in the Prediction of Intracranial Aneurysm Wall Shear
      Stress: The 2015 International Aneurysm CFD Challenge.
AB  - PURPOSE: Image-based computational fluid dynamics (CFD) is widely used to predict
      intracranial aneurysm wall shear stress (WSS), particularly with the goal of
      improving rupture risk assessment. Nevertheless, concern has been expressed over
      the variability of predicted WSS and inconsistent associations with rupture.
      Previous challenges, and studies from individual groups, have focused on
      individual aspects of the image-based CFD pipeline. The aim of this Challenge was
      to quantify the total variability of the whole pipeline. METHODS: 3D rotational
      angiography image volumes of five middle cerebral artery aneurysms were provided
      to participants, who were free to choose their segmentation methods, boundary
      conditions, and CFD solver and settings. Participants were asked to fill out a
      questionnaire about their solution strategies and experience with aneurysm CFD,
      and provide surface distributions of WSS magnitude, from which we objectively
      derived a variety of hemodynamic parameters. RESULTS: A total of 28 datasets were
      submitted, from 26 teams with varying levels of self-assessed experience. Wide
      variability of segmentations, CFD model extents, and inflow rates resulted in
      interquartile ranges of sac average WSS up to 56%, which reduced to < 30% after
      normalizing by parent artery WSS. Sac-maximum WSS and low shear area were more
      variable, while rank-ordering of cases by low or high shear showed only modest
      consensus among teams. Experience was not a significant predictor of variability.
      CONCLUSIONS: Wide variability exists in the prediction of intracranial aneurysm
      WSS. While segmentation and CFD solver techniques may be difficult to standardize
      across groups, our findings suggest that some of the variability in image-based
      CFD could be reduced by establishing guidelines for model extents, inflow rates,
      and blood properties, and by encouraging the reporting of normalized hemodynamic
      parameters.

PMID- 30203116
TI  - Factors Associated with Sport-Related Post-concussion Headache and Opportunities
      for Treatment.
AB  - PURPOSE OF REVIEW: The purpose of this review is to (1) describe factors both pre
      and post-injury that are associated with post-concussion headache, (2) describe
      the influence of post-concussion headache on recovery following concussion, and
      (3) provide potential post-concussion treatment options that may reduce the
      burden of headache, as well as other symptoms to facilitate recovery. RECENT
      FINDINGS: Various factors may be associated with post-concussion headache
      presentation. These may include pre-injury or historical factors such as sex,
      family and self-history of headache and migraine, concussion history, and mood
      disorders. In addition, post-injury presentation factors for consideration may
      include injury mechanism, symptom clusters, cervicogenic dysfunction, and post
      concussion physiologic dysfunction. Despite this complex interplay of factors,
      many treatment options may improve headache symptoms and recovery post-concussion
      including rehabilitation programs focusing on deficits such as visual-vestibular
      dysfunction, sub-symptom threshold exercise, and potential pharmacological
      interventions. Concussion is a complex injury that results in a variety of
      sequelae with headache being one of the most common. Understanding factors
      related to post-concussion headache presentation and the available options for
      treatment may improve patient care and outcomes post-concussion.

PMID- 30203117
TI  - Effects of positive end-expiratory pressure strategy in supine and prone position
      on lung and chest wall mechanics in acute respiratory distress syndrome.
AB  - BACKGROUND: In acute respiratory distress syndrome (ARDS) patients, it has
      recently been proposed to set positive end-expiratory pressure (PEEP) by
      targeting end-expiratory transpulmonary pressure. This approach, which relies on
      the measurement of absolute esophageal pressure (Pes), has been used in supine
      position (SP) and has not been investigated in prone position (PP). Our purposes
      were to assess Pes-guided strategy to set PEEP in SP and in PP as compared with a
      PEEP/FIO2 table and to explore the early (1 h) and late (16 h) effects of PP on
      lung and chest wall mechanics. RESULTS: We performed a prospective, physiologic
      study in two ICUs in university hospitals on ARDS patients with PaO2/FIO2 < 150
      mmHg. End-expiratory Pes (Pes,ee) was measured in static (zero flow) condition.
      Patients received PEEP set according to a PEEP/FIO2 table then according to the
      Pes-guided strategy targeting a positive (3 +/- 2 cmH2O) static end-expiratory
      transpulmonary pressure in SP. Then, patients were turned to PP and received same
      amount of PEEP from PEEP/FIO2 table then Pes-guided strategy. Respiratory
      mechanics, oxygenation and end-expiratory lung volume (EELV) were measured after
      1 h of each PEEP in each position. For the rest of the 16-h PP session, patients
      were randomly allocated to either PEEP strategy with measurements done at the
      end. Thirty-eight ARDS patients (27 male), mean +/- SD age 63 +/- 13 years, were
      included. There were 33 primary ARDS and 26 moderate ARDS. PaO2/FIO2 ratio was
      120 +/- 23 mmHg. At same PEEP/FIO2 table-related PEEP, Pes,ee averaged 9 +/- 4
      cmH2O in both SP and PP (P = 0.88). With PEEP/FIO2 table and Pes-guided strategy,
      PEEP was 10 +/- 2 versus 12 +/- 4 cmH2O in SP and 10 +/- 2 versus 12 +/- 5 cmH2O
      in PP (PEEP strategy effect P = 0.05, position effect P = 0.96, interaction P =
      0.96). With the Pes-guided strategy, chest wall elastance increased regardless of
      position. Lung elastance and transpulmonary driving pressure decreased in PP,
      with no effect of PEEP strategy. Both PP and Pes-guided strategy improved
      oxygenation without interaction. EELV did not change with PEEP strategy. At the
      end of PP session, respiratory mechanics did not vary but EELV and PaO2/FIO2
      increased while PaCO2 decreased. CONCLUSIONS: There was no impact of PP on Pes
      measurements. PP had an immediate improvement effect on lung mechanics and a late
      lung recruitment effect independent of PEEP strategy.

PMID- 30203119
TI  - Association between age at menopause and fracture risk: a systematic review and
      meta-analysis.
AB  - PURPOSE: Early menopause (EM, age at menopause < 45 years) and premature ovarian
      insufficiency (POI, age at menopause < 40 years) are associated with an increased
      risk of osteoporosis. However, their association with increased fracture risk has
      not been established, with studies yielding conflicting results. The primary aim
      of this systematic review and meta-analysis was to synthesize studies evaluating
      the association between age at menopause and fracture risk. The secondary aim was
      to evaluate this effect concerning the site of fractures. METHODS: A
      comprehensive search was conducted in PubMed, CENTRAL and Scopus, up to 31
      January 2018. Data were expressed as odds ratio (OR) with 95% confidence
      intervals (CI). The I2 index was employed for quantifying heterogeneity. RESULTS:
      Eighteen studies were included in the qualitative and quantitative analysis
      (462,393 postmenopausal women, 12,130 fractures). Compared with women with age at
      menopause > 45 years, women with EM demonstrated higher fracture risk (OR 1.36,
      95% CI 1.11-1.66, p < 0.002, I2 81.5%). Women with POI did not display any
      difference in fracture risk compared either with women with age at menopause > 40
      (OR 1.23, 95% CI 0.72-2.09, p = 0.436, I2 62.5%) or >45 years (OR 0.54, 95% CI
      0.22-1.29, p = 0.17, I2 0%). No difference was evident when a separate analysis
      was performed for vertebral, non-vertebral and hip fractures. CONCLUSIONS: This
      is the first meta-analysis showing that EM is associated with increased fracture
      risk compared with normal age at menopause, without any distinct effect on the
      site of the fracture.

PMID- 30203121
TI  - Correction to: Adrenocortical incidentalomas and bone: from molecular insights to
      clinical perspectives.
AB  - The original version of this article unfortunately contained a mistake in Figure
      1. There is a typo in the word "osteoclastogenesis" and the word "activity" is
      missing in the same entity. It should be "osteoclastogenesis" instead of
      "osteoclestogenesis".

PMID- 30203120
TI  - Dynamic changes in the distribution of facial and abdominal adipose tissue
      correlated with surgical treatment in acromegaly.
AB  - PURPOSE: Acromegaly is a systemic metabolic disease. Growth hormone (GH) have a
      significant impact on adipose tissue (AT). A huge reduction of serum GH after
      surgical treatment may cause substantial AT redistribution. The objective of this
      study was to illustrate the dynamic changes in distribution of facial and
      abdominal AT correlated with surgical treatment in patients with acromegaly.
      METHODS: Abdominal AT in 17 acromegaly patients (group 1) was studied
      longitudinally preoperatively and 1 month to 1 year postoperatively. The facial
      and abdominal subcutaneous AT (fSAT and aSAT) of another 17 acromegaly patients
      (group 2) were compared with 7 nonfunctional pituitary adenoma (NFPA) controls.
      The areas of fSAT, aSAT, and visceral adipose tissue (VAT) were obtained by MRI
      and quantified by image analysis software, and intrahepatic lipid (IHL) was
      assessed by 1H magnetic resonance spectroscopy (MRS). RESULTS: Abdominal adipose
      tissue (aSAT, VAT, and IHL) increased overall after surgical treatment. However,
      IHL first decreased and then continuously increased during the follow-up.
      Compared with the increased amount of aSAT, the fSAT amount decreased after
      surgical treatment. The inconsistency of this phenomenon did not appear in the
      NFPA control subjects. CONCLUSION: The perioperative dynamic distribution of the
      facial and abdominal fat in acromegaly revealed regional differences in the
      intricate effect of GH on adipose tissue. Reduction of serum GH after surgical
      treatment of acromegaly was associated with dynamic increases of IHL, abdominal
      visceral, and subcutaneous fat, but a reduction of facial subcutaneous fat.

PMID- 30203123
TI  - Single and multiple ascending-dose study of glucagon-receptor antagonist RN909 in
      type 2 diabetes: a phase 1, randomized, double-blind, placebo-controlled trial.
AB  - PURPOSE: This first-in-human study assessed safety, immunogenicity,
      pharmacokinetics, and pharmacodynamics of RN909, a monoclonal antibody antagonist
      of the glucagon receptor, in type 2 diabetes (T2DM) subjects. METHODS: This study
      enrolled 84 T2DM subjects receiving stable metformin regimens. Forty-four
      subjects were randomized to receive single escalating doses of RN909 (0.3 to 6
      mg/kg subcutaneously (SC), or 1 mg/kg intravenously (IV)), or placebo; 40
      subjects were randomized to receive multiple escalating doses (50 to 150 mg SC)
      or placebo every 4 weeks for 12 weeks. RESULTS: RN909 was well tolerated;
      treatment-related elevated liver function tests (LFTs) were observed in 4/33
      (12.1%) and 5/32 (15.6%) subjects treated with single and multiple doses,
      respectively, versus 1/10 (10%) and 0 in the respective placebo groups. RN909
      dose-normalized AUCinf increased more than dose-proportionally following single
      SC doses, and after multiple doses, accumulation ratios ranged from 1.3 to 3.4.
      The incidence of antidrug antibodies (ADA) was 33% after single doses and 50%
      after multiple doses. RN909 produced dose-dependent, durable fasting plasma
      glucose (FPG)-lowering at day 29 (mean change -20.6 to -97.5 mg/dL) and day 85
      (mean change; -27.2 to -43.5 mg/dL) after single and multiple doses,
      respectively. HbA1c also was reduced after single (mean change -0.30% to -1.44%),
      and multiple doses (-0.83% to -1.56%). CONCLUSION: RN909 was well tolerated after
      single and multiple doses in T2DM subjects, with diarrhea and elevated LFTs the
      most frequent adverse events. The appearance of ADA did not affect
      pharmacokinetics or efficacy. Robust lowering of FPG and HbA1c was observed.

PMID- 30203122
TI  - Ectopic thyroids have lower computed tomography attenuation values than
      orthotopic thyroids.
AB  - PURPOSE: To determine whether ectopic thyroid had the same computed tomography
      (CT) value as orthotopic thyroid. METHODS: Twenty-one patients with 23 ectopic
      thyroids and 23 controls with orthotopic thyroids underwent CT scans and were
      included in this retrospective study. The CT images were reviewed in a blinded
      fashion by two radiologists. Independent-Samples T-test was used for comparison
      of CT attenuation values between two groups. RESULTS: Ectopic thyroids had
      significantly lower non-enhanced attenuation (91.04 +/- 5.97 Hounsfield Units vs.
      106.56 +/- 4.06 Hounsfield Units, P = 0.038) and contrast-enhanced attenuation
      (141.32 +/- 6.42 Hounsfield Units vs. 169.82 +/- 4.30 Hounsfield Units, P =
      0.001) values than orthotopic thyroids. CONCLUSIONS: Ectopic thyroids have lower
      CT attenuation values than orthotopic thyroids probably due to the structural or
      functional abnormalities. The dysgenesis and pathological changes of the ectopic
      thyroids may contribute to functional deficiency which finally leads to decrease
      of the CT attenuation values.

PMID- 30203124
TI  - Impaired glucagon secretion in patients with fulminant type 1 diabetes mellitus.
AB  - PURPOSE: Fulminant type 1 diabetes mellitus (FT1DM), characterized by rapid and
      almost complete destruction of pancreatic beta-cells, is a newly identified
      subtype of type 1 diabetes mellitus. Although, the pathophysiology of this
      condition remains still unclear, histological evidence suggests that not only
      beta-cells but also alpha-cells of pancreatic islets are reduced in number in
      FT1DM. However, the ability of glucagon secretion in patients with this condition
      has remained largely uncharacterized. We therefore examined glucagon secretion in
      patients with FT1DM and compared that with patients with other types of diabetes
      mellitus. METHODS: Fasting glucagon levels as well as glucagon secretion induced
      by intravenous administration of arginine were measured in hospitalized 83
      patients with diabetes mellitus, including 4 with FT1DM, 18 with type 1 diabetes
      mellitus (T1DM), 40 with type 2 diabetes mellitus (T2DM), 5 with slowly
      progressive insulin-dependent diabetes mellitus (SPIDDM), and 16 with pancreatic
      diabetes mellitus (PDM). RESULTS: The area under the curve for serum glucagon
      levels after arginine infusion in FT1DM patients was significantly smaller than
      that in T1DM, T2DM, or SPIDDM patients but was similar to that in PDM patients.
      The fasting serum glucagon level of FT1DM patients was lower than that of T1DM or
      T2DM patients but did not significantly differ from that of SPIDDM or PDM
      patients. CONCLUSIONS: These results suggest that glucagon secretion is impaired
      in patients with FT1DM.

PMID- 30203126
TI  - 4-D flow MRI aortic 3-D hemodynamics and wall shear stress remain stable over
      short-term follow-up in pediatric and young adult patients with bicuspid aortic
      valve.
AB  - BACKGROUND: Children with bicuspid aortic valve (BAV) are at risk for serious
      complications including aortic valve stenosis and aortic rupture. Most studies
      investigating biomarkers predictive of BAV complications are focused on adults.
      OBJECTIVE: To investigate whether hemodynamic parameters change over time in
      children and young adults with BAV by comparing baseline and follow-up four
      dimensional (4-D) flow MRI examinations. MATERIALS AND METHODS: We
      retrospectively included 19 children and young adults with BAV who had serial 4-D
      flow MRI exams (mean difference in scan dates 1.8+/-1.0 [range, 0.6-3.4 years]).
      We compared aortic peak blood flow velocity, three-dimensional (3-D) wall shear
      stress, aortic root and ascending aortic (AAo) z-scores between baseline and
      follow-up exams. We generated systolic streamlines for all patients and visually
      compared their baseline and follow-up exams. RESULTS: The only significant
      difference between baseline and follow-up exams occurred in AAo z-scores (3.12+/
      2.62 vs. 3.59+/-2.76, P<0.05) indicating growth of the AAo out of proportion to
      somatic growth. There were no significant changes in either peak velocity or 3-D
      wall shear stress between baseline and follow-up exams. Ascending aortic peak
      velocity at baseline correlated with annual change in AAo z-score (r=0.58,
      P=0.009). Visual assessment revealed abnormal blood flow patterns, which were
      unique to each patient and remained stable between baseline and follow-up exams.
      CONCLUSION: In our pediatric and young adult BAV cohort, hemodynamic markers and
      systolic blood flow patterns remained stable over short-term follow-up despite
      significant AAo growth, suggesting minimal acute disease progression. Baseline
      AAo peak velocity was a predictor of AAo dilation and might help in determining
      pediatric patients with BAV who are at risk of increased AAo growth.

PMID- 30203127
TI  - Tamoxifen administration and the risk of Parkinsonism.

PMID- 30203128
TI  - Tamoxifen administration and risk of Parkinson's disease.

PMID- 30203129
TI  - Graphical representation of network meta-analysis: an iconographic support to the
      complexity of multiple data comparisons.

PMID- 30203130
TI  - Phase reduction and phase-based optimal control for biological systems: a
      tutorial.
AB  - A powerful technique for the analysis of nonlinear oscillators is the rigorous
      reduction to phase models, with a single variable describing the phase of the
      oscillation with respect to some reference state. An analog to phase reduction
      has recently been proposed for systems with a stable fixed point, and phase
      reduction for periodic orbits has recently been extended to take into account
      transverse directions and higher-order terms. This tutorial gives a unified
      treatment of such phase reduction techniques and illustrates their use through
      mathematical and biological examples. It also covers the use of phase reduction
      for designing control algorithms which optimally change properties of the system,
      such as the phase of the oscillation. The control techniques are illustrated for
      example neural and cardiac systems.

PMID- 30203125
TI  - Cardiovascular stents: overview, evolution, and next generation.
AB  - Compared to bare-metal stents (BMSs), drug-eluting stents (DESs) have been
      regarded as a revolutionary change in coronary artery diseases (CADs). Releasing
      pharmaceutical agents from the stent surface was a promising progress in the
      realm of cardiovascular stents. Despite supreme advantages over BMSs, in-stent
      restenosis (ISR) and long-term safety of DESs are still deemed ongoing concerns
      over clinically application of DESs. The failure of DESs for long-term clinical
      use is associated with following factors including permanent polymeric coating
      materials, metallic stent platforms, non-optimal drug releasing condition, and
      factors that have recently been supposed as contributory factors such as
      degradation products of polymers, metal ions due to erosion and degradation of
      metals and their alloys utilizing in some stents as metal frameworks. Discovering
      the direct relation between stent materials and associating adverse effects is a
      complicated process, and yet it has not been resolved. For clinical success it is
      of significant importance to optimize DES design and explore novel strategies to
      overcome all problems including inflammatory response, delay endothelialization,
      and sub-acute stent thrombosis (ST) simultaneously. In this work, scientific
      reports are reviewed particularly focusing on recent advancements in DES design
      which covers both potential improvements of existing and recently novel prototype
      stent fabrications. Covering a wide range of information from the BMSs to recent
      advancement, this study mostly sheds light on DES's concepts, namely stent
      composition, drug release mechanism, and coating techniques. This review further
      reports different forms of DES including fully biodegradable DESs, shape-memory
      ones, and polymer-free DESs.

PMID- 30203132
TI  - Role of pentamer complex-specific and IgG subclass 3 antibodies in HCMV
      hyperimmunoglobulin and standard intravenous IgG preparations.
AB  - BACKGROUND: HCMV hyperimmunoglobulin-preparations (HIG) contain high
      concentrations of HCMV-specific IgG. The reduced maternofetal-HCMV-transmission
      rate of IgG may be due to HCMV-specific neutralizing antibodies against the HCMV
      pentameric complex (PC). In contrast to HIG, standard intravenous immunoglobulin
      (IVIG) may have more neutralization (NT) capacity than HIG due to higher IgG
      subclass 3 levels (Planitzer et al., 2011). METHODS: We investigated the HCMV
      specific NT-capacity of HIG Cytotect(r), using a recombinant pentameric complex
      (gHgLUL128-131A) for specific antibody-depletion. We used a modified UL130
      peptide (TANQNPSPPWSKLTYSKPH) based on original-sequence of Saccoccio et al.
      (Vaccine 29(15):2705-2711, 2011) (SWSTLTANQNPSPPWSKLTY) as neutralization target.
      Both UL130-peptides and the PC were bound via sixfold HisTag and anti-HisTag mAbs
      to magnetic beads to deplete HCMV-specific IgGs from HIG (Cytotect(r)). Modifying
      this depletion strategy, we analyzed the role of IgG subclass 3 in both HIG and
      IVIG. RESULTS: After CMV IgG-normalization of HIG and IVIG, we found a
      significant trend towards a decrease (16%) of neutralization-capacity for the
      UL130 TAN-peptide, but not for the original UL130 SWS-peptide. However, highly
      significant loss of NT-capacity could be only observed by PC depletion (42%). The
      IgG subclass 3 depletion revealed no significant reduction of NT-capacity in both
      HIG and IVIG. CONCLUSION: Via specific antibody depletion, we could demonstrate
      that pentameric complex-specific antibodies are present in HIG and bind to the
      recombinant PC resulting in a highly significant reduction of NT-capacity
      compared to the UL130 TAN-and SWS-peptides. We could not confirm the functional
      role of IgG subclass 3 neutralizing antibodies in IgG-preparations.

PMID- 30203133
TI  - The sequence analysis of Epstein-Barr virus EBNA1 gene: could viral screening
      markers for nasopharyngeal carcinoma be identified?
AB  - Epstein-Barr virus (EBV) has been identified as a group 1 carcinogenic agent,
      particularly for nasopharyngeal carcinoma (NPC). The sequence diversity of EBV
      nuclear antigen 1 (EBNA1) reflects region-restricted polymorphisms, which may be
      associated with the development of certain malignancies. The aims of the present
      study were to evaluate EBV EBNA1 gene polymorphisms circulating in NPC,
      infectious mononucleosis, and isolates from patients with transplanted organs to
      determine if EBNA1 sequence specificities are useful as viral biomarkers for NPC.
      Forty biopsies of undifferentiated carcinoma of nasopharyngeal type (UCNT), 31
      plasma samples from patients with mononucleosis syndrome, and 16 plasma samples
      from patients after renal transplantation were tested in this study. The EBNA1
      gene was amplified by nested PCR. Further investigation included sequencing,
      phylogenetic, and statistical evaluations. Eighty-seven sequences were identified
      as one of the four EBNA1 subtypes, P-Ala, P-Thr, V-Val, and V-Ala, with further
      classification into ten subvariants. Of these, P-Thr-sv-1 and P-Thr-sv-3 have
      never been identified in Europe, while V-Val-sv-1 was newly discovered.
      Statistical analysis revealed significant differences in the distribution of
      EBNA1 P-Thr subvariants between the three groups of patients, with noticeable
      clustering of P-Thr-sv-5 in NPC isolates (p < 0.001). EBV EBNA1 showed no
      sequence specificity in primary infection. This research revealed a newly
      discovered EBNA1 subvariant. Importantly, EBNA1 P-Thr-sv-5 showed carcinoma
      specific EBNA1 variability. Thus, identification of this subvariant should be
      considered as a viral screening marker for NPC or UCNT.

PMID- 30203134
TI  - Graphene-Assisted Thermal Interface Materials with a Satisfied Interface Contact
      Level Between the Matrix and Fillers.
AB  - Reduced graphene oxide (RGO) and three-dimensional graphene networks (3DGNs) are
      adopted to improve the performance of thermal interface materials (TIMs).
      Therein, the 3DGNs provide a fast transport network for phonons, while the RGO
      plays as a bridge to enhance the phonon transport ability at the interface
      between the filler and matrix. The types of surface functional groups of the RGO
      are found to exert a remarkable influence on the resulting thermal performance;
      the carboxyl groups are found in the optimal selection to promote the transport
      process at the interface area because a strong chemical bond will form between
      the graphene basal plane and epoxy resin (ER) through this kind of group. The
      resulting thermal conductivity reaches 6.7 Wm-1 K-1 after optimizing the mass
      fraction and morphology of the filler, which is 3250% higher than that of the
      pristine ER. Moreover, the mechanical properties of these as-prepared TIMs are
      also detected, and the specimens by using the RGO(OOH) filler display the better
      performances.

PMID- 30203131
TI  - Exploitation of Bacillus subtilis as a robust workhorse for production of
      heterologous proteins and beyond.
AB  - Bacillus subtilis, belonging to the type species of Bacillus, is a type of soil
      derived, low %G+C, endospore-forming Gram-positive bacterium. After the discovery
      of B. subtilis 168 that displayed natural competence, this bacterium has been
      intensively considered to be an ideal model organism and a robust host to study
      several basic mechanisms, such as metabolism, gene regulation, bacterial
      differentiation, and application for industrial purposes, such as heterologous
      protein expression and the overproduction of an array of bioactive molecules.
      Since the first report of heterologous overproduction of recombinant proteins in
      this strain, the bulk production of a multitude of valuable enzymes, especially
      industrial enzymes, has been performed on a relatively large scale. Since B.
      subtilis can non-specifically secrete recombinant proteins using various signal
      peptides, it has tremendous advantages over Gram-negative bacterial hosts. Along
      with the report of the complete genome sequence of B. subtilis, a number of
      genetic tools, including diverse types of plasmids, bacterial promoters,
      regulatory elements, and signal peptides, have been developed and characterized.
      These novel genetic elements tremendously accelerated genetic engineering in B.
      subtilis recombinant systems. In addition, with the development of several
      complex gene expression systems, B. subtilis has performed a number of more
      complex functions. This ability enables it to be a substantial chassis in
      synthetic biology rather than just a workhorse for the overproduction of
      recombinant proteins. In this review, we review the progress in the development
      of B. subtilis as a universal platform to overproduce heterologous diverse high
      value enzymes. This progress has occurred from the development of biological
      parts, including the characterization and utilization of native promoters, the
      fabrication of synthetic promoters and regulatory elements, and the assembly and
      optimization of genetic systems. Some important industrial enzymes that have been
      produced in large quantities in this host are also summarized in this review.
      Furthermore, the ability of B. subtilis to serve as a cellular tool was also
      briefly recapitulated and reviewed.

PMID- 30203136
TI  - Identification of differentially expressed genes and signaling pathways using
      bioinformatics in interstitial lung disease due to tyrosine kinase inhibitors
      targeting the epidermal growth factor receptor.
AB  - Interstitial lung disease (ILD) is a rare but lethal adverse effect of epidermal
      growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) treatment. The
      specific mechanism of this disease is not fully understood. To systematically
      analyze genes associated with EGFR-TKI induced ILD, gene data of EGFR-TKI induced
      ILD were extracted initially using text mining, and then the intersection between
      genes from text mining and Gene Expression Omnibus (GEO) dataset was taken for
      further protein-protein interaction (PPI) analysis using String-bd database. Go
      ontology (GO) and pathway enrichment analysis was also conducted based on
      Database of Annotation, Visualization and Integrated Discovery (DAVID) platform.
      The PPI network generated by STRING was visualized by Cytoscape, and the topology
      scores, functional regions and gene annotations were analyzed using plugins of
      CytoNCA, molecular complex detection (MCODE) and ClueGo. 37 genes were identified
      as EGFR-TKI induced ILD related. Gene enrichment analysis yield 18 enriched GO
      terms and 12 associated pathways. A PPI network that included 199 interactions
      for a total of 35 genes was constructed. Ten genes were selected as hub genes
      using CytoNCA plugin, and four highly connected clusters were identified using
      MCODE plugin. GO and pathway annotation analysis for the cluster one revealed
      that five genes were associated with either response to dexamethasone or with
      lung fibrosis, including CTGF, CCL2, IGF1, EGFR and ICAM1. Our data might be
      useful to reveal the pathological mechanisms of EGFR-TKI induced ILD and provide
      evidence for the diagnosis and treatment in the future.

PMID- 30203137
TI  - Versatility of uniplanar prearthoplastic distraction osteogenesis in the
      correction of post-ankylosis facial deformities-a report of five different cases.
AB  - PURPOSE: Unilateral or bilateral ankylosis can lead to severe micrognathia and
      facial deformity that requires multiple, often, staged surgical corrections. To
      date, there is no ideal treatment modality that satisfactorily corrects the
      complex anatomy, restores the ramal height, and corrects the micrognathia and
      microgenia. Distraction osteogenesis has been acclaimed as a successful modality
      for the treatment of such deformities. It is a cost-effective approach with low
      morbidity and less relapse thus providing better functional and esthetic
      outcomes. It allows the surgeon to correct the deformity in various planes by
      using various devices by changing osteotomy designs and vectors, with
      simultaneous hard tissue and soft tissue reconstruction. PATIENTS AND METHODS:
      Here, we present a series of five cases where different types of distraction
      osteogenesis were combined with various other procedures to correct post
      ankylotic facial asymmetry. In one case, simultaneous maxillo-mandibular
      distraction [Molina's technique] was used. RESULTS: All patients showed
      significant improvement in function and esthetics. Outcome assessment was made
      using clinical photographs and radiographs. CONCLUSION: Pre-arthroplastic
      distraction osteogenesis is a versatile cost effective approach that can be
      customized for every patient based on their needs.

PMID- 30203139
TI  - Correction to: Neolithic phylogenetic continuity inferred from complete
      mitochondrial DNA sequences in a tribal population of Southern India.
AB  - Unfortunately, the original version of this article was published with an error
      in the second sentence of the 'Molecular dating' section.

PMID- 30203138
TI  - Voxel-wise analysis of dynamic 18F-FET PET: a novel approach for non-invasive
      glioma characterisation.
AB  - BACKGROUND: Glioma grading with dynamic 18F-FET PET (0-40 min p.i.) is typically
      performed by analysing the mean time-activity curve of the entire tumour or a
      suspicious area within a heterogeneous tumour. This work aimed to ensure a reader
      independent glioma characterisation and identification of aggressive sub-volumes
      by performing a voxel-based analysis with diagnostically relevant kinetic and
      static 18F-FET PET parameters. One hundred sixty-two patients with a newly
      diagnosed glioma classified according to histologic and molecular genetic
      properties were evaluated. The biological tumour volume (BTV) was segmented in
      static 20-40 min p.i. 18F-FET PET images using the established threshold of 1.6 *
      background activity. For each enclosed voxel, the time-to-peak (TTP), the late
      slope (Slope15-40), and the tumour-to-background ratios (TBR5-15, TBR20-40)
      obtained from 5 to 15 min p.i. and 20 to 40 min p.i. images were determined. The
      percentage portion of these values within the BTV was evaluated with percentage
      volume fractions (PVFs) and cumulated percentage volume histograms (PVHs). The
      ability to differentiate histologic and molecular genetic classes was assessed
      and compared to volume-of-interest (VOI)-based parameters. RESULTS: Aggressive
      WHO grades III and IV and IDH-wildtype gliomas were dominated by a high
      proportion of voxels with an early peak, negative slope, and high TBR, whereby
      the PVHs with TTP < 20 min p.i., Slope15-40 < 0 SUV/h, and TBR5-15 and TBR20-40 >
      2 yielded the most significant differences between glioma grades. We found
      significant differences of the parameters between WHO grades and IDH mutation
      status, where the effect size was predominantly higher for voxel-based PVHs
      compared to the corresponding VOI-based parameters. A low overlap of BTV sub
      volumes defined by TTP < 20 min p.i. and negative Slope15-40 with TBR5-15 > 2-
      and TBR20-40 > 2-defined hotspots was observed. CONCLUSIONS: The presented
      approach applying voxel-wise analysis of dynamic 18F-FET PET enables an enhanced
      characterisation of gliomas and might potentially provide a fast identification
      of aggressive sub-volumes within the BTV. Parametric 3D 18F-FET PET information
      as investigated in this study has the potential to guide individual therapy
      instrumentation and may be included in future biopsy studies.

PMID- 30203140
TI  - A Game-Theoretic Model of Cholera with Optimal Personal Protection Strategies.
AB  - Cholera is an acute gastro-intestinal infection that affects millions of people
      throughout the world each year, primarily but not exclusively in developing
      countries. Because of its public health ramifications, considerable mathematical
      attention has been paid to the disease. Here we consider one neglected aspect of
      combating cholera: personal participation in anti-cholera interventions. We
      construct a game-theoretic model of cholera in which individuals choose whether
      to participate in either vaccination or clean water consumption programs under
      assumed costs. We find that relying upon individual compliance significantly
      lowers the incidence of the disease as long as the cost of intervention is
      sufficiently low, but does not eliminate it. The relative costs of the measures
      determined whether a population preferentially adopts a single preventative
      measure or employs the measure with the strongest early adoption.

PMID- 30203141
TI  - Control of Pyragas Applied to a Coupled System with Unstable Periodic Orbits.
AB  - We apply a Pyragas-type control in order to synchronize the solutions of a
      glycolytic model that exhibits an aperiodic behavior. This delay control is used
      to stabilize the orbits of ordinary differential nonlinear equations systems.
      Inspired by several works that studied the chaotic behavior of diverse systems
      for the enzymatic reactions in the presence of feedbacks, the control to two of
      these models is analyzed.

PMID- 30203142
TI  - Transverse debridement and acute shortening followed by distraction histogenesis
      in the treatment of open tibial fractures with bone and soft tissue loss.
AB  - This retrospective case series evaluates the technique of transverse debridement,
      acute shortening and subsequent distraction histogenesis in the management of
      open tibial fractures with bone and soft tissue loss, thereby avoiding the need
      for a soft tissue flap to cover the wound. Thirty-one patients with Gustilo grade
      III open tibial fractures between 2001 and 2011 were initially managed with
      transverse wound extensions, debridement and shortening to provide bony
      apposition and allowing primary wound closure without tension, or coverage with
      mobilization of soft tissue and split skin graft. Temporary monolateral external
      fixation was used to allow soft tissues resuscitation, followed by Ilizarov frame
      for definitive fracture stabilization. Leg length discrepancy was corrected by
      corticotomy and distraction histogenesis. Union was evaluated radiologically and
      clinically. Patients' mean age was 37.3 years (18.3-59.3). Mean bone defect was
      3.2 cm (1-8 cm). Mean time to union was 40.1 weeks (12.6-80.7 weeks), and median
      frame index was 75 days/cm. Median lengthening index (time in frame after
      corticotomy for lengthening) was 63 days/cm. Mean clinic follow-up was 79 weeks
      (23-174). Six patients had a total of seven complications. Four patients re
      fractured after frame removal, one of whom required a second frame. Two patients
      required a second frame for correction of residual deformity, and one patient
      developed a stiff non-union which united following a second frame. There were no
      cases of deep infection. Acute shortening followed by distraction histogenesis is
      a safe method for the acute treatment of open tibial fractures with bone and soft
      tissue loss. This method also avoids the cost, logistical issues and morbidity
      associated with the use of local or free-tissue transfer flaps and has a low rate
      of serious complications despite the injury severity.

PMID- 30203144
TI  - Nitrous oxide emissions from biofilm processes for wastewater treatment.
AB  - This paper discusses the microbial basis and the latest research on nitrous oxide
      (N2O) emissions from biofilms processes for wastewater treatment. Conditions that
      generally promote N2O formation in biofilms include (1) low DO values, or spatial
      DO transitions from high to low within the biofilm; (2) DO fluctuations within
      biofilm due to varying bulk DO concentrations or varying substrate
      concentrations; (3) conditions with high reaction rates, which lead to greater
      formation of intermediates, e.g., hydroxylamine (NH2OH) and nitrite (NO2-), that
      promote N2O formation; and (4) electron donor limitation for denitrification.
      Formation of N2O directly results from the activities of ammonia-oxidizing
      bacteria (AOB), ammonia-oxidizing archaea (AOA), and heterotrophic denitrifying
      bacteria. More research is needed on the roles of AOA, comammox, and specialized
      denitrifying microorganisms. In nitrifying biofilms, higher bulk ammonia (NH3)
      concentrations, higher nitrite (NO2-) concentrations, lower dissolved oxygen
      (DO), and greater biofilm thicknesses result in higher N2O emissions. In
      denitrifying biofilms, N2O accumulates at low levels as an intermediate and at
      higher levels at the oxic/anoxic transition regions of the biofilms and where COD
      becomes limiting. N2O formed in the outer regions can be consumed in the inner
      regions if COD penetrates sufficiently. In membrane-aerated biofilms, where
      nitrification takes place in the inner, aerobic biofilm region, the exterior
      anoxic biofilm can serve as a N2O sink. Reactors that include variable aeration
      or air scouring, such as denitrifying filters, trickling filters, or rotating
      biological contactors (RBCs), can form peaks of N2O emissions during or following
      a scouring or aeration event. N2O emissions from biofilm processes depend on the
      microbial composition, biofilm thickness, substrate concentrations and
      variability, and reactor type and operation. Given the complexity and difficulty
      in quantifying many of these factors, it may be difficult to accurately predict
      emissions for full-scale treatment plants. However, a better understanding of the
      mechanisms and the impacts of process configurations can help minimize N2O
      emission from biofilm processes for wastewater treatment.

PMID- 30203145
TI  - Thermophilic biodesulfurization and its application in oil desulfurization.
AB  - To reduce the harm caused to the environment by fuel combustion and meet the
      increasingly stringent emission standards, the sulfur content of fuels should be
      reduced. Dibenzothiophene, benzothiophene, and their derivatives are sulfur
      containing components of fuels that are difficult to desulfurize and can
      therefore cause great environmental damage. Biodesulfurization is a
      desulfurization method that has the advantage of being able to remove
      dibenzothiophene and its derivatives removed easily under conditions that are
      relatively mild when compared with hydrodesulfurization. This paper introduces
      the advantages of thermophilic biodesulfurization compared with mesophilic
      biodesulfurization; analyzes the desulfurization mechanism, including the
      desulfurization pathways and enzymic systems of desulfurization bacteria; and
      discusses the application of biodesulfurization in oil desulfurization. The main
      problems existing in biodesulfurization and possible solutions are also analyzed
      in this paper. Biological desulfurization is a promising method for
      desulfurization; accordingly, more studies investigating biodesulfurization of
      actual oil are needed to enable the industrialized application of
      biodesulfurization.

PMID- 30203143
TI  - Myofibrillar myopathy in the genomic context.
AB  - Myofibrillar myopathy (MFM) is a group of inherited muscular disorders
      characterized by myofibril dissolution and abnormal accumulation of degradation
      products. The diagnosis of muscular disorders based on clinical presentation is
      difficult due to phenotypic heterogeneity and overlapping symptoms. In addition,
      precise diagnosis does not always explain the disease etiopathology or the highly
      variable clinical course even among patients diagnosed with the same type of
      myopathy. The advent of high-throughput next-generation sequencing (NGS) has
      provided a successful and cost-effective strategy for identification of novel
      causative genes in myopathies, including MFM. So far, pathogenic mutations
      associated with MFM phenotype, including atypical MFM-like cases, have been
      identified in 17 genes: DES, CRYAB, MYOT, ZASP, FLNC, BAG3, FHL1, TTN, DNAJB6,
      PLEC, LMNA, ACTA1, HSPB8, KY, PYROXD1, and SQSTM + TIA1 (digenic). Most of these
      genes are also associated with other forms of muscle diseases. In addition, in
      many MFM patients, numerous genomic variants in muscle-related genes have been
      identified. The various myopathies and muscular dystrophies seem to form a single
      disease continuum; therefore, gene identification in one disease impacts the
      genetic etiology of the others. In this review, we describe the heterogeneity of
      the MFM genetic background focusing on the role of rare variants, the importance
      of whole genome sequencing in the identification of novel disease-associated
      mutations, and the emerging concept of variant load as the basis of the
      phenotypic heterogeneity.

PMID- 30203146
TI  - Endophytic fungi isolated from medicinal plants: future prospects of bioactive
      natural products from Tabebuia/Handroanthus endophytes.
AB  - Medicinal plants are a rich source of natural products used to treat many
      diseases; therefore, they are the basis for a new drug discovery. Plants are
      capable of generating different bioactive secondary metabolites, but a large
      amount of botanical material is often necessary to obtain small amounts of the
      target substance. Nowadays, many medicinal plants are becoming rather scarce. For
      this reason, it is important to point out the interactions between endophytic
      microorganisms and the host plant, because endophytes are able to produce highly
      diverse compounds, including those from host plants that have important
      biological activities. Thence, this review aims at presenting the richness in
      bioactive compounds of the medicinal plants from Tabebuia and Handroanthus
      genera, as well as important aspects about endophyte-plant interactions, with
      emphasis on the production of bioactive compounds by endophytic fungi, which has
      been isolated from various medicinal plants for such a purpose. Furthermore, bio
      prospection of natural products synthesized by endophytes isolated from the
      aforementioned genera used in traditional medicine could be used to treat
      illnesses.

PMID- 30203147
TI  - Correlation of genomic alterations between tumor tissue and circulating tumor DNA
      by next-generation sequencing.
AB  - PURPOSE: Analysis of circulating tumor DNA (ctDNA) offers an unbiased and
      noninvasive way to assess the genetic profiles of tumors. This study aimed to
      analyze mutations in ctDNA and their correlation with tissue mutations in
      patients with a variety of cancers. METHODS: We included 21 cancer patients
      treated with surgical resection for whom we collected paired tissue and plasma
      samples. Next-generation sequencing (NGS) of all exons was performed in a
      targeted human comprehensive cancer panel consisting of 275 genes. RESULTS: Six
      patients had at least one mutation that was concordant between tissue and ctDNA
      sequencing. Among all mutations (n = 35) detected by tissue and blood sequencing,
      20% (n = 7) were concordant at the gene level. Tissue and ctDNA sequencing
      identified driver mutations in 66.67% and 47.62% of the tested samples,
      respectively. Tissue and ctDNA NGS detected actionable alterations in 57.14% and
      33.33% of patients, respectively. When somatic alterations identified by each
      test were combined, the total proportion of patients with actionable mutations
      increased to 71.43%. Moreover, variants of unknown significance that were judged
      likely pathogenic had a higher percentage in ctDNA exclusively. Across six
      representative genes (PIK3CA, CTNNB1, AKT1, KRAS, TP53, and MET), the sensitivity
      and specificity of detection using mutations in tissue sample as a reference were
      25 and 96.74%, respectively. CONCLUSIONS: This study indicates that tissue NGS
      and ctDNA NGS are complementary rather than exclusive approaches; these data
      support the idea that ctDNA is a promising tool to interrogate cancer genetics.

PMID- 30203148
TI  - Variability in HER2 expression between primary colorectal cancer and
      corresponding metastases.
AB  - PURPOSE: This study aimed to investigate the HER2 status of primary colorectal
      cancer (CRC) and corresponding metastases, and determine the correlation between
      HER2 and clinicopathological characteristics. METHODS: We collected the
      clinicopathological features of 98 CRC patients and 66 patients which were
      previously evaluated for the KRAS status. The tissue samples of primary CRC
      tumors (n = 98), noninvolved colorectal mucosa (n = 98), paired lymph nodes (n =
      98, 69 patients had positive metastatic nodes), and liver metastases (n = 22)
      were evaluated using immunohistochemistry for HER2. The kappa test was used to
      evaluate the concordance rate of HER2 status. Survival analysis was established
      according to the Kaplan-Meier method. RESULTS: HER2 overexpression was more
      common in primary tumors among the younger patients (P < 0.05). No survival
      significance was revealed in the HER2 status. The HER2-positive rate was 11.2%
      for the primary CRC tumors, 0% for the normal adjacent mucosa tissues, 10.1% for
      the matched positive lymph nodes, and 31.8% for the corresponding metastasis.
      Seven of sixty-nine cases (10.1%) exhibited biomarker discordance in nodal
      metastases compared with primary tumors (kappa = 0.48, P < 0.05); 6 out of 22
      cases (27.3%) exhibited biomarker discrepancy in liver metastases compared with
      primary tumors (kappa = 0.32, P > 0.05). Compared with lymph nodes, HER2
      overexpression in the primary tissue was more common in KRAS wild-type patients
      (P < 0.05). CONCLUSIONS: The present study showed a high rate of discordance in
      matched pairs of primary tumors and metastases, suggesting that the accurate
      evaluation of HER2 status is essential before any therapeutic decision.

PMID- 30203151
TI  - Targeting HMGB1/TLR4 axis and miR-21 by rosuvastatin: role in alleviating
      cholestatic liver injury in a rat model of bile duct ligation.
AB  - Many pathways are involved in the association between biliary obstruction and
      liver injury. We investigated the intervention influence and effect of
      rosuvastatin (Rvs) on the high mobility group protein 1 (HMGB1)/toll-like
      receptor-4 (TLR4) axis and microRNA-21 (miR-21) in cholestatic liver injury. This
      model was performed by ligating common bile duct of Wistar rats. Saline and Rvs
      were orally administrated by gastric gavages. Liver and blood samples were
      collected and subjected to molecular and biochemical evaluation. We found that
      the daily oral administration of Rvs was protective against the occurrence of
      cholestatic liver injury. This was evident from the results of hepatic, oxidative
      stress, and inflammatory biomarkers. This study also revealed the Rvs inhibitory
      effect on the HMGB1/TLR4 intracellular signaling axis as evidenced by decreasing
      the levels of nuclear factor kappabeta (NFkappabeta), tumor necrosis factor alpha
      (TNFalpha), and interleukin 6 (IL6) production. Furthermore, Rvs-treated group
      showed a significant reduction in the expression of miR-21 in comparison to the
      untreated group. Accordingly, rosuvastatin interference with the HMGB1/TLR4 and
      miR-21 expression could explain its hepatoprotective effect in cholestatic liver
      injury.

PMID- 30203149
TI  - Catheter-Based Renal Denervation for Hypertension.
AB  - PURPOSE OF REVIEW: This review was undertaken to update readers on the field of
      therapeutic renal denervation for hypertension during the 2016 through 2018
      period. RECENT FINDINGS: After the failure of Symplicity HTN-3 to meet its top
      line objective, intense scrutiny revealed several possible concerns addressed by
      the newer investigations into the area of renal denervation. These included
      better device technology, more intense subject monitoring for off-protocol
      antihypertensive drug usage, and deeper penetration into the renal vasculature by
      the interventionist. Whether untreated by medication for hypertension or on
      antihypertensive medication, renal denervation shows a clear, though moderate,
      blood pressure reduction. The failure of roughly one out of three patients with
      hypertension to respond to denervation procedures argues that there is room for
      improvement in choosing the optimal patient for this approach to hypertension
      management.

PMID- 30203150
TI  - The heat shock protein 70 gene as a new alternative molecular marker for the
      taxonomic identification of Streptomyces strains.
AB  - With the developments in taxonomy, the classically used highly conserved 16S rRNA
      molecular marker has shown some disadvantages among closely related species. For
      further taxonomic studies of the prokaryotes, specific PCR primers were designed
      from two conserved regions in the amino acid sequences of the 70-kDa heat shock
      protein sourced from 20 different genera in actinomycetes. These were used for
      the amplification of the hsp70 genes in 16 Streptomyces strains. Then, we
      investigated the phylogenetic relationships among these Streptomyces strains and
      compared the tree topology based on the hsp70 gene with those based on the
      previously used markers (16S rRNA and gyrB). To our knowledge, this is the first
      use of the hsp70 gene as a molecular marker for the taxonomic identification of
      Streptomyces.

PMID- 30203152
TI  - Incorporating Technology into the Psychiatric Residency Curriculum.

PMID- 30203153
TI  - [Value of combining biologics with methotrexate for treatment of psoriatic
      arthritis-questions remain].
AB  - BACKGROUND: Concomitant methotrexate (MTX) improves the therapeutic effect of
      biologic therapies in rheumatoid arthritis treatment. However, the influence of
      MTX on biologic therapy in psoriasis arthritis (PsA) has not yet been fully
      clarified, as data from randomized clinical studies are lacking. So far, it is
      only known, that PsA patients with inadequate response to MTX or non-steroidal
      anti-inflammatory drugs alone respond equally well to a subsequent biologic
      therapy. OBJECTIVES: The aim of this study is to investigate whether MTX-naive
      patients achieve greater disease improvement with the combination of MTX and a
      biologic than with biologic monotherapy alone, and whether patients on MTX in
      whom a biologic therapy is additionally started would worsen if MTX is
      discontinued. METHODS: The current data situation and its limitations are
      presented. Furthermore, an investigator-initiated multicenter randomized clinical
      study in patients with active PsA is introduced (MUST study), which investigates
      the influence of placebo-controlled MTX combination therapy with the interleukin
      12/23 inhibitor ustekinumab (UST) in order to close the existing evidence gap.
      RESULTS: The primary objective of the study is to demonstrate the non-inferiority
      of UST monotherapy compared to MTX/UST combination therapy as measured by mean
      DAS28 values at week 24. Of 196 planned patients, 77 have been included so far.
      Recruitment is still open. CONCLUSION: The MUST study offers the ideal
      opportunity to investigate the influence of concomitant MTX in a controlled study
      design and to assess whether the addition of MTX to UST therapy or its
      continuation is beneficial for PsA patients.

PMID- 30203154
TI  - An expanded fish-based index of biotic integrity for Great Lakes coastal
      wetlands.
AB  - Biotic indicators are useful for assessing ecosystem health because the structure
      of resident communities generally reflects abiotic conditions integrated over
      time. We used fish data collected over 5 years for 470 Great Lakes coastal
      wetlands to develop multi-metric indices of biotic integrity (IBI). Sampling and
      IBI development were stratified by vegetation type within each wetland to account
      for differences in physical habitat. Metrics were evaluated against numerous
      indices of anthropogenic disturbance derived from water quality and surrounding
      land-cover variables. Separate datasets were used for IBI development and
      testing. IBIs were composed of 10-11 metrics for each of four vegetation types
      (bulrush, cattail, water lily, and submersed aquatic vegetation). Scores of all
      IBIs correlated well with disturbance indices using the development data, and the
      accuracy of our IBIs was validated using the testing data. Our fish IBIs can be
      used to prioritize wetland protection and restoration efforts across the Great
      Lakes basin. The IBIs will also be useful in monitoring programs mandated by the
      Agreement between Canada and the United States of America on Great Lakes Water
      Quality, such as for assessing Beneficial Use Impairments (BUIs) in Great Lakes
      Areas of Concern, and in other ecosystem management programs in Canada and the
      USA.

PMID- 30203155
TI  - Influence of the Substrate to the LSP Coupling Wavelength and Strength.
AB  - Three kinds of typical structures, hemi-/spherical nanoparticles/nanoparticle
      dimers on the substrate and spherical nanoparticles/nanoparticle dimers half
      buried into the substrate, are used for FDTD simulation to theoretically discuss
      the influence of the substrate to the localized surface plasmon (LSP) coupling
      when the metal nanoparticles/nanoparticle dimers are locating near a substrate.
      Simulated results show that the dependencies between the LSP coupling wavelength
      and the refractive index of the substrate for different structures are not the
      same, which can be attributed to the different polarization field distributions
      of LSPs. When light is incident from different directions, the LSP coupling
      strength are not the same as well and the ratios of the scattering peak
      intensities depend on the position of the metal nanoparticles or nanoparticle
      dimers. These phenomenon can be explained by the difference of the local driving
      electric field intensities which is modulated by the interface between the air
      and the substrate.

PMID- 30203158
TI  - Improved nucleic acid extraction protocols for Ganoderma boninense, G.
      miniatocinctum and G. tornatum.
AB  - The first and most crucial step of all molecular techniques is to isolate high
      quality and intact nucleic acids. However, DNA and RNA isolation from fungal
      samples are usually difficult due to the cell walls that are relatively
      unsusceptible to lysis and often resistant to traditional extraction procedures.
      Although there are many extraction protocols for Ganoderma species, different
      extraction protocols have been applied to different species to obtain high yields
      of good quality nucleic acids, especially for genome and transcriptome
      sequencing. Ganoderma species, mainly G. boninense causes the basal stem rot
      disease, a devastating disease that plagues the oil palm industry. Here, we
      describe modified DNA extraction protocols for G. boninense, G. miniatocinctum
      and G. tornatum, and an RNA extraction protocol for G. boninense. The modified
      salting out DNA extraction protocol is suitable for G. boninense and G.
      miniatocinctum while the modified high salt and low pH protocol is suitable for
      G. tornatum. The modified DNA and RNA extraction protocols were able to produce
      high quality genomic DNA and total RNA of ~ 140 to 160 ug/g and ~ 80 ug/g of
      mycelia respectively, for Single Molecule Real Time (PacBio Sequel(r) System) and
      Illumina sequencing. These protocols will benefit those studying the oil palm
      pathogens at nucleotide level.

PMID- 30203159
TI  - Investigation on the Cultivation Conditions of a Newly Isolated Fusarium Fungal
      Strain for Enhanced Lipid Production.
AB  - Fusarium equiseti UMN-1 fungal strain isolated from soybean is selected as a
      potential oleaginous fungal strain for biodiesel generation. It possesses
      desirable features, such as high lipid content (up to 56%) and high fatty acid
      methyl ester (FAME) content (more than 98%) in total lipids, and also has the
      capability to produce cellulase. This research focused on the investigation of
      the characteristics of this strain and optimization of culture conditions to
      enhance lipid production. Impact of temperature, agitation, C/N ratio, medium
      composition, and carbon and nitrogen sources has been observed, and central
      composite design (CCD) has been applied to improve the lipid accumulation. The
      optimum range for temperature, agitation, C/N ratio, and carbon and nitrogen
      concentrations was discovered, and the CCD model with the optimized growth medium
      and growth conditions achieved a maximum lipid production of 3.89 g/L. This
      research on F. equiseti UMN-1 fungal strain is expected to improve the
      feasibility of using microbial lipids of F. equiseti UMN-1 strains as the source
      of biofuels.

PMID- 30203157
TI  - Olfactory sensitivity for mold-associated odorants in CD-1 mice and spider
      monkeys.
AB  - Using operant conditioning procedures, we assessed the olfactory sensitivity of
      six CD-1 mice and three spider monkeys for mold-associated odorants. We found
      that with all eight stimuli, the mice detected concentrations as low as 0.1 ppm
      (parts per million), and with two of them individual animals even detected
      concentrations as low as 1 ppt (parts per trillion). The spider monkeys detected
      concentrations as low as 4 ppm with all eight stimuli, and with four of them
      individual animals even detected concentrations as low as 4 ppb (parts per
      billion). Between-species comparisons showed that with all eight odorants, the
      mice displayed significantly lower threshold values, that is, a higher
      sensitivity than the spider monkeys, but not than human subjects tested in
      previous studies. Analysis of odor structure-activity relationships showed that
      in both species, the type of oxygen-containing functional group and the presence
      versus absence of a double bond as well as the length of the carbon backbone of
      the odor stimuli had a systematic effect on detectability. We conclude that both
      mice and spider monkeys are clearly able to detect the presence of molds and thus
      to assess the palatability of potential food using the volatiles produced by
      molds during putrefaction.

PMID- 30203160
TI  - Ultrastructure and secretion of glandular trichomes in species of subtribe
      Cajaninae Benth (Leguminosae, Phaseoleae).
AB  - The subtribe Cajaninae of papilionoid legumes has a pantropical distribution and
      comprises approximately 490 species. These species have diversified throughout
      dry environments where there are high temperatures and strong light. The subtribe
      stands out because all its representatives have vesicular glands. In addition,
      bulbous-based and capitate trichomes are important secretory structures present
      in all genera of the Cajaninae. We analyzed the ultrastructure and histochemistry
      of these glandular trichome types in leaflets of the three species of the
      subtribe. Using transmission electron microscopy and histochemical analyses, we
      link the glandular secretions to subcellular structures. We here report for the
      first time the type of exudate and ultrastructure of the glands of subtribe
      Cajaninae. Terpenoids and phenolics were confirmed by histochemistry tests, and
      we observed that the organelles responsible for biosynthesis of oils are the most
      representative in these glands. Each glandular trichome showed particular
      ultrastructural features compatible with the compounds produced. We suggest that
      these glandular trichomes, with their respective exudates, act in defense against
      herbivory and against possible damage by ultraviolet radiation.

PMID- 30203161
TI  - A comparison of homonym meaning frequency estimates derived from movie and
      television subtitles, free association, and explicit ratings.
AB  - Most words are ambiguous, with interpretation dependent on context. Advancing
      theories of ambiguity resolution is important for any general theory of language
      processing, and for resolving inconsistencies in observed ambiguity effects
      across experimental tasks. Focusing on homonyms (words such as bank with
      unrelated meanings EDGE OF A RIVER vs. FINANCIAL INSTITUTION), the present work
      advances theories and methods for estimating the relative frequency of their
      meanings, a factor that shapes observed ambiguity effects. We develop a new
      method for estimating meaning frequency based on the meaning of a homonym evoked
      in lines of movie and television subtitles according to human raters. We also
      replicate and extend a measure of meaning frequency derived from the
      classification of free associates. We evaluate the internal consistency of these
      measures, compare them to published estimates based on explicit ratings of each
      meaning's frequency, and compare each set of norms in predicting performance in
      lexical and semantic decision mega-studies. All measures have high internal
      consistency and show agreement, but each is also associated with unique variance,
      which may be explained by integrating cognitive theories of memory with the
      demands of different experimental methodologies. To derive frequency estimates,
      we collected manual classifications of 533 homonyms over 50,000 lines of
      subtitles, and of 357 homonyms across over 5000 homonym-associate pairs. This
      database-publicly available at: www.blairarmstrong.net/homonymnorms/ -constitutes
      a novel resource for computational cognitive modeling and computational
      linguistics, and we offer suggestions around good practices for its use in
      training and testing models on labeled data.

PMID- 30203162
TI  - Examining cross-level effects in dyadic analysis: A structural equation modeling
      perspective.
AB  - The actor-partner interdependence (APIM) and common-fate (CFM) models for dyadic
      data are well understood and widely applied. The actor and partner coefficients
      estimated in the APIM reflect the associations between individual-level variance
      components, whereas the CFM coefficient describes the association between dyad
      level variance components. Additionally, both models assume that the
      theoretically relevant and/or empirically dominant component of variability
      resides at the same level (individual or dyad) across the predictor and outcome
      variables. The present work recasts the APIM and CFM in terms of dyadic
      nonindependence, or the extent to which a given variable reflects dyad- versus
      individual-level processes, and describes a pair of hybrid actor-partner and
      common-fate models that connect variance components residing at different levels.
      A series of didactic examples illustrate how the traditional APIM and CFM can be
      combined with the hybrid models to describe mediational processes that span the
      individual and dyad levels.

PMID- 30203165
TI  - Correction to: One decade of glioblastoma multiforme surgery in 342 elderly
      patients: what have we learned?
AB  - There was a typo in the third author's name in the initial online publication.

PMID- 30203163
TI  - Patients' perspective on the burden of migraine in Europe: a cross-sectional
      analysis of survey data in France, Germany, Italy, Spain, and the United Kingdom.
AB  - BACKGROUND: Migraine is a distinct neurological disease that imposes a
      significant burden on patients, society, and the healthcare system. This study
      aimed to characterize the incremental burden of migraine in individuals who
      suffer from >=4 monthly headache days (MHDs) by examining health-related quality
      of life (HRQoL), impairments to work productivity and daily activities, and
      healthcare resource utilization (HRU) in the EU5 (France, Germany, Italy, Spain,
      United Kingdom). METHODS: This retrospective cross-sectional study used data from
      the 2016 National Health and Wellness Survey (NHWS; N = 80,600). Short-Form 36
      Item Health Survey, version 2 (SF-36v2) physical and mental component summary
      scores (PCS and MCS), Short-form-6D (SF-6D), and EuroQoL (EQ-5D), impairments to
      work productivity and daily activities (Work Productivity and Activity Impairment
      Questionnaire (WPAI), and HRU were compared between migraine respondents
      suffering from >=4 MHDs (n = 218) and non-migraine controls (n = 218) by
      propensity score matching using sociodemographic characteristics. Chi-square, T
      tests, and Mann-Whitney tests were performed to determine significant differences
      between the groups after propensity score matching. RESULTS: HRQoL was lower in
      migraine individuals suffering from >=4 MHDs compared with non-migraine controls,
      with reduced SF-36v2 PCS (46.00 vs 50.51) and MCS (37.69 vs 44.82), SF-6D health
      state utility score (0.62 vs 0.71), and EQ-5D score (0.68 vs 0.81) (for all, p <
      0.001). Respondents with migraine suffering from >=4 MHDs also reported higher
      levels of absenteeism from work (14.43% vs 9.46%; p = 0.001), presenteeism
      (35.52% vs 20.97%), overall work impairment (38.70% vs 23.27%), and activity
      impairment (44.17% vs 27.75%) than non-migraine controls (for all, p < 0.001).
      Additionally, HRU was significantly higher for individuals with >=4 MHDs compared
      to their matched controls. Consistently, migraine subgroups (4-7 MHDs, 8-14 MHDs
      and CM) had lower HRQoL, greater overall work and activity impairment, and higher
      HRU compared to non-migraine controls. CONCLUSIONS: Migraine of >=4 MHDs was
      associated with poorer HRQoL, greater work productivity loss, and higher HRU
      compared with non-migraine controls. The findings of the study suggest that an
      unmet need exists among individuals suffering from >=4 MHDs in the EU5 suggesting
      the need for effective prophylactic treatments to lessen the humanistic and
      economic burden of migraine.

PMID- 30203164
TI  - Mesophyll conductance to CO2 in leaves of Siebold's beech (Fagus crenata)
      seedlings under elevated ozone.
AB  - Ozone is an air pollutant that negatively affects photosynthesis in woody plants.
      Previous studies suggested that ozone-induced reduction in photosynthetic rates
      is mainly attributable to a decrease of maximum carboxylation rate (Vcmax) and/or
      maximum electron transport rate (Jmax) estimated from response of net
      photosynthetic rate (A) to intercellular CO2 concentration (Ci) (A/Ci curve)
      assuming that mesophyll conductance for CO2 diffusion (gm) is infinite. Although
      it is known that Ci-based Vcmax and Jmax are potentially influenced by gm, its
      contribution to ozone responses in Ci-based Vcmax and Jmax is still unclear. In
      the present study, therefore, we analysed photosynthetic processes including gm
      in leaves of Siebold's beech (Fagus crenata) seedlings grown under three levels
      of ozone (charcoal-filtered air or ozone at 1.0- or 1.5-times ambient
      concentration) for two growing seasons in 2016-2017. Leaf gas exchange and
      chlorophyll fluorescence were simultaneously measured in July and September of
      the second growing season. We determined the A, stomatal conductance to water
      vapor and gm, and analysed A/Ci curve and A/Cc curve (Cc: chloroplast CO2
      concentration). We also determined the Rubisco and chlorophyll contents in
      leaves. In September, ozone significantly decreased Ci-based Vcmax. At the same
      time, ozone decreased gm, whereas there was no significant effect of ozone on Cc
      based Vcmax or the contents of Rubisco and chlorophyll in leaves. These results
      suggest that ozone-induced reduction in Ci-based Vcmax is a result of the
      decrease in gm rather than in carboxylation capacity. The decrease in gm by
      elevated ozone was offset by an increase in Ci, and Cc did not differ depending
      on ozone treatment. Since Cc-based Vcmax was also similar, A was not changed by
      elevated ozone. We conclude that gm is an important factor for reduction in Ci
      based Vcmax of Siebold's beech under elevated ozone.

PMID- 30203167
TI  - Absence of Promoter Mutation in TBC1D12 Gene in Solid and Hematologic Neoplasia.

PMID- 30203166
TI  - Clinical outcomes of radiotherapy for spinal cord ependymoma with adverse
      prognostic features: a single-center study.
AB  - PURPOSE: This study evaluated the outcomes of radiotherapy (RT) for spinal
      ependymoma with adverse features, such as incomplete resection or disseminated
      disease. METHODS: Twenty-five patients underwent RT for spinal cord ependymoma
      during 1991-2016. Twenty-four patients had gross disease on the pre-RT spinal
      magnetic resonance images. Six patients (24%) had disseminated disease. The World
      Health Organization grades were I (12 patients), II (12 patients), and III (1
      patient). The RT fields were the tumor bed plus margin in 19 patients (76%), the
      entire craniospinal axis in 5 patients (20%), and the entire spinal canal with
      posterior cranial fossa in 1 patient (4%). The median RT dose was 50.4 Gy (range
      44.0-59.4 Gy). RESULTS: The median follow-up was 49 months (range 9-321 months),
      with 5-year overall and progression-free survival rates of 83.7% and 70.8%,
      respectively. Relative to patients with grade II/III ependymoma, patients with
      grade I ependymoma had higher 5-year rates of overall survival (100% vs. 69.4%, P
      = .088) and progression-free survival (100% vs. 42.3%, P = .02). Disease
      progression was observed in 4 patients who had grade II ependymoma, including 2
      of 6 patients with disseminated disease and 2 of 19 patients with localized
      disease. Twelve patients (48%) exhibited improved neurological function. One
      patient who underwent craniospinal irradiation developed late hypopituitarism. No
      other RT-related late toxicities were observed. CONCLUSIONS: Favorable survival
      outcomes were achieved using RT for spinal ependymoma with adverse prognostic
      features. Thus, RT may be an effective treatment option when complete tumor
      removal cannot be achieved.

PMID- 30203168
TI  - [Endoscopic management of complications after laparoscopic sleeve gastrectomy].
AB  - Laparoscopic sleeve gastrectomy (SG) is currently the most commonly performed
      standalone bariatric procedure worldwide. Gastric staple line leakage is the
      feared immanent complication of the operation, which is difficult to treat and
      often persists. This article presents the endoscopic treatment options for
      complications after laparoscopic SG, particularly the treatment of gastric staple
      line leakage. Most important for a successful treatment is the understanding of
      the underlying pathophysiological causes, the exact surgical comprehension of the
      procedure and advanced endoscopic skills. The choice of endoscopic intervention
      depends on the available strategies as well as on the skills of the executing
      endoscopist. Currently, internal drainage seems to be the most expedient method.

PMID- 30203169
TI  - [Triclosan-coated sutures in colorectal surgery : Assessment and meta-analysis of
      the recommendations of the WHO guideline].
AB  - BACKGROUND: In the global guidelines for the prevention of surgical site
      infections (SSI), the World Health Organization (WHO) recommends the general use
      of triclosan-coated sutures irrespective of the type of surgical intervention.
      OBJECTIVE: Can this recommendation on the use of triclosan-coated sutures be
      confirmed by a meta-analysis specifically for colorectal surgery? METHODS:
      Randomized and non-randomized clinical trials comparing triclosan-coated and
      uncoated sutures for the efficacy in reducing the SSI rate in colorectal surgery
      were identified by a systematic literature review. In addition, various quality
      criteria were set for the studies to be included: SSI definition according to the
      Centers for Disease Control and Prevention (CDC), a priori sample size
      calculation and a maximum SSI rate of 20%. The odds ratios were pooled using a
      fixed and random effects model, the 95% confidence intervals (CI) were calculated
      and subgroup analyses were carried out. RESULTS: Included in the meta-analysis
      were 3 prospective randomized trials (RCT) and 3 non-randomized trials involving
      a total of 2957 subjects. The average SSI rate was 6.90% (76/1101) in the
      triclosan group and 9.11% (169/1856) in the control group, resulting in an odds
      ratio of 0.62 (95% CI: 0.29-1.31). Subgroup analysis showed a decreased risk for
      SSI in monocentric trials (OR = 0.39, 95% CI: 0.25-0.60) but an increased SSI
      risk in multicenter trials (OR = 1.75, 95% CI: 1.11-2.77). CONCLUSION: Against
      the background of a moderate to high risk of bias and the partially contradictory
      findings of the studies, the general recommendation of the WHO on the use of
      triclosan-coated sutures for colorectal surgery could not be confirmed.

PMID- 30203170
TI  - Cardiovascular recovery after workload in German shift workers in the hotel and
      catering industry: results of 24-hour-ambulatory monitoring of heart rate and
      blood pressure.
AB  - PURPOSE: Shift work is associated with an impairment of sleep-wake cycles that
      can affect cardiovascular recovery (CR) negatively. The aim of this study was to
      examine CR of shift and day workers in the hotel and catering industry (HCI) and
      identify predictors of CR. METHODS: The sample consisted of 64 alternating and 96
      day workers in the HCI. Monitoring of blood pressure (BP) and heart rate (HR) was
      conducted for 24 hours per working day during work, leisure and sleep. The CR
      process was examined for differences between work and leisure, work and sleep
      regarding a reduction in BP and HR. Lifestyle (physical activity, smoking,
      drinking) was assessed through questionnaires, BP over a four-day, self
      assessment period (38% hypertensives). Participants taking BP medication (n = 12)
      were excluded from analyses. RESULTS: Shift workers had significantly higher BP
      (O 146/87 vs. O 140/84 mmHg; p = 0.034-0.044) and HR (O 86 vs. 82 bpm; p = 0.032)
      during their work phase verses day workers. There were no differences found for
      the CR between work and leisure nor work and sleep. As predictors of the CR,
      classic cardiovascular indicators (blood pressure status, smoking, age, physical
      activity, sex) were found which explains between 14% (HR) and 30% (BP) of the
      variance. Shift work was not a predictor for CR. CONCLUSIONS: Employees in the
      HCI show that their CR is mainly determined by the known cardiovascular
      indicators and less by shift work. This effect needs to be discussed in relation
      to the job requirements and the cardiovascular health of the employees.

PMID- 30203171
TI  - [YAG laser vitreolysis for treatment of symptomatic vitreous opacities].
AB  - YAG laser vitreolysis is an innovative procedure to treat symptomatic vitreous
      floaters. The treatment decision is based on taking a comprehensive patient
      history, thorough clinical examination, realistic expectations, and detailed
      patient information including risk of the procedure. Manifestation of vitreous
      opacities and possible subjective impairments are considerably variable. Dynamic
      changes over time are possible. Therefore, not all vitreous opacities are
      suitable for laser treatment. A classification according to histoanatomical
      origin can aid the treatment decision. In comparison to other ophthalmic YAG
      laser applications, YAG laser vitreolysis differs predominantly by its specific
      technical equipment requirements. In addition, treatment is more complex and time
      consuming, requires appropriate experience and knowledge of the surgeon, and
      should be carried out with utmost care and accuracy.

PMID- 30203172
TI  - Inactivation of spores by nonthermal plasmas.
AB  - Bacterial and fungal spore contamination in different industries has a greater
      economic impact. Because of the remarkable resistance of spores to most physical
      and chemical microbicidal agents, their inactivation need special attention
      during sterilization processes. Heat and chemical sporicides are not always well
      suited for different sterilization/decontamination applications and carries
      inherent risks. In recent years, novel nonthermal agents including nonthermal
      plasmas are emerging as effective sporicides against a broad spectrum of
      bacterial and fungal spores. The present review discusses various aspects related
      to the inactivation of spores using nonthermal plasmas. Different types of both
      low pressure plasmas (e.g., capacitively coupled plasma and microwave plasma) and
      atmospheric pressure plasmas (e.g., dielectric barrier discharges, corona
      discharges, arc discharges, radio-frequency-driven plasma jet) have been
      successfully applied to destroy spores of economic significance. Plasma agents
      contributing to sporicidal activity and their mode of action in inactivation are
      discussed. In addition, information on factors that affect the sporicidal action
      of nonthermal plasmas is included.

PMID- 30203173
TI  - Mesoporous Silicon Microspheres Produced from In Situ Magnesiothermic Reduction
      of Silicon Oxide for High-Performance Anode Material in Sodium-Ion Batteries.
AB  - Sodium-ion batteries have been widely used in energy storage owing to its high
      sodium content and low cost. This study proves that mesoporous silicon
      microspheres (MSMs) with the homogeneously distributed mesopores ranging from 1
      to 10 nm can be used as anodes of NIBs. In situ magnesiothermic reduction of
      silicon oxide was carried out to synthesize the MSM samples. An anode in NIBs was
      tested, and it was observed that the MSMs sample which was calcined at 650 
      degrees C had a good rate performance of 160 mAh g-1 at 1000 mAg-1 and a high
      reversible capacity of 390 mAh g-1 at 100 mAg-1 after 100 cycles. Moreover, its
      long-term cycling performance was 0.08 mAh g-1 decay per cycle for 100 cycles,
      which was quite excellent. MSMs have high reversibility, good cycling
      performance, and excellent rate capability, which are related to its ultrafine
      particle size and mesoporous morphology.

PMID- 30203175
TI  - Comparison of bone marrow component removal from processed femoral head bone from
      living and deceased donors: presence of geodes in living donor bone can prevent
      maximum removal of marrow components.
AB  - NHS Blood and Transplant Tissue and Eye Services banks and issues, cut, shaped
      and washed bone from deceased donors. The bone is cut/shaped prior to washing and
      then processed to remove up to 99.9% of blood, bone marrow and associated cells.
      The processed bone is then sterilised by gamma irradiation with or without a
      freeze-drying step. Removal of donor blood and bone marrow has been reported to
      aid incorporation of allograft bone without affecting the biomechanical
      properties of the bone. However, cut and shaped bone is not suitable for some
      orthopaedic procedures and some orthopaedic surgeons do not wish to use
      irradiated bone. Therefore, Tissue and Eye Services have also developed a method
      for washing intact femoral head bone, from living and deceased donors. We have
      observed that processing of intact femoral head bone does not always result in
      removal of 99% (or above) of marrow components and can be as low as 93% removal.
      We have examined washed femoral head bone and found the presence of internal
      fluid-filled cysts within subchondral cancellous bone in bone from living donors.
      The cysts have been identified as geodes and we suggest that these geodes may be
      responsible for the reduction in bone marrow component removal in living donor
      bone during processing.

PMID- 30203174
TI  - Usefulness of preoperative three-dimensional volumetric analysis of carotid body
      tumors.
AB  - PURPOSE: The Shamblin classification is the commonest method to predict
      complications and outcomes during carotid body tumor (CBT) resection. The aim of
      this study is to describe the utility of the three-dimensional volumetric
      reconstruction (3DVR) analysis of the CBT and its relationship with postoperative
      outcomes. METHODS: Preoperative computed tomography angiography (CTA) was
      obtained to perform 3DVR of the CBT. Imaging data were analyzed and correlated
      with surgical outcomes: estimated blood loss (EBL), surgical time (ST), and
      hospital length of stay (HLOS). The Pearson test was used to determine the
      correlation between volume and postoperative outcomes. RESULTS: Fifty-seven
      patients were studied, 13 had Shamblin type I tumors with a mean 3DVR of 7.69 cm3
      (standard deviation [SD 8.27]), 21 were type II with a mean 3DVR of 15.57 cm3 (SD
      8.40), and 23 were type III with a mean 3DVR of 30.58 cm3 (SD 20.16). EBL mean
      was 559 milliliters (mL) (standard error [SE] 80.44), the mean ST of resection
      was 202 min (SD 67), and the mean HLOS was 5.8 days (SD 3.23). The Pearson test
      showed a correlation of r = 0.69 (p < 0.0001) between 3DVR and EBL, a r = 0.4 (p
      = 0.05) was obtained between 3DVR and ST, and finally, a r = 0.3 (p = 0.05)
      between 3DVR and HLOS was obtained. CONCLUSION: The preoperative 3DVR
      determination of CBTs allows to analyze possible predictors of surgical outcomes.
      We found a positive correlation between the 3DVR volume and EBL. Further research
      is necessary to validate this method in the evaluation of these rare neoplasms.

PMID- 30203176
TI  - Home sleep apnea testing: comparison of manual and automated scoring across
      international sleep centers.
AB  - PURPOSE: To determine the agreement between the manual scoring of home sleep
      apnea tests (HSATs) by international sleep technologists and automated scoring
      systems. METHODS: Fifteen HSATs, previously recorded using a type 3 monitor, were
      saved in European Data Format. The studies were scored by nine experienced
      technologists from the sleep centers of the Sleep Apnea Global Interdisciplinary
      Consortium (SAGIC) using the locally available software. Each study was scored
      separately by human scorers using the nasal pressure (NP), flow derived from the
      NP signal (transformed NP), or respiratory inductive plethysmography (RIP) flow.
      The same procedure was followed using two automated scoring systems: Remlogic
      (RLG) and Noxturnal (NOX). RESULTS: The intra-class correlation coefficients
      (ICCs) of the apnea-hypopnea index (AHI) scoring using the NP, transformed NP,
      and RIP flow were 0.96 [95% CI 0.93-0.99], 0.98 [0.96-0.99], and 0.97 [0.95
      0.99], respectively. Using the NP signal, the mean differences in AHI between the
      average of the manual scoring and the automated systems were - 0.9 +/- 3.1/h
      (AHIRLG vs AHIMANUAL) and - 1.3 +/- 2.6/h (AHINOX vs AHIMANUAL). Using the
      transformed NP, the mean differences in AHI were - 1.9 +/- 3.3/h (AHIRLG vs
      AHIMANUAL) and 1.6 +/- 3.0/h (AHINOX vs AHIMANUAL). Using the RIP flow, the mean
      differences in AHI were - 2.7 +/- 4.5/h (AHIRLG vs AHIMANUAL) and 2.3 +/- 3.4/h
      (AHINOX vs AHIMANUAL). CONCLUSIONS: There is very strong agreement in the scoring
      of the AHI for HSATs between the automated systems and experienced international
      technologists. Automated scoring of HSATs using commercially available software
      may be useful to standardize scoring in future endeavors involving international
      sleep centers.

PMID- 30203177
TI  - Arsenic Bioremediation by Indigenous Heavy Metal Resistant Bacteria of Fly Ash
      Pond.
AB  - Fly ash (FA), the major by-product of coal-fired thermal power plants, causes
      significant environmental degradation owing to its injurious heavy metal
      contents. Leaching of arsenic (As) from ash ponds is especially significant as As
      released from FA can increase As concentration of drinking water above maximum
      contaminant level of 10 ppb. The aim of this paper was demonstration of As
      bioremediation potential of indigenous As resistant bacteria present in the
      weathered pond ash sample. Ten isolates belonging to Bacillus, Micrococcus,
      Kytococcus and Staphylococcus genera were characterized. Biochemical tests showed
      reduction of relatively non toxic arsenate to more toxic arsenite by two strains
      while four strains showed oxidation of arsenite to arsenate. Two
      exoplolysaccharide producing strains were shown to absorb As within their
      biomass. Total heterotrophs versus As resistant heterotrophs counting performed
      showed that FA was enriched with As resistant heterotrophs. Column leaching based
      microcosm study revealed overall As detoxification potential of the isolated
      microbes.

PMID- 30203178
TI  - Fuzzy entropy based on differential evolution for breast gland segmentation.
AB  - For the diagnosis and treatment of breast tumors, the automatic detection of
      glands is a crucial step. The true segmentation of the gland is directly related
      to effective treatment effect of the patient. Therefore, it is necessary to
      propose an automatic segmentation algorithm based on mammary gland features. A
      segmentation method of differential evolution (DE) fuzzy entropy based on mammary
      gland is proposed in the paper. According to the image fuzzy entropy, the
      evaluation function of image segmentation is constructed in the first step. Then,
      the method adopts DE, the image fuzzy entropy parameter is regard as the initial
      population of individual. After the mutation, crossover and selection of three
      evolutionary processes to search for the maximum fuzzy entropy of parameters, the
      optimal threshold of the segmented gland is achieved. Finally, the mammary gland
      is segmented by the threshold method of maximum fuzzy entropy. Eight breast
      images with four tissue types are tested 100 times, with accuracy (Acc),
      sensitivity (Sen), specificity (Spe), positive predictive value (PPV), negative
      predicted value (NPV), and average structural similarity (Mssim) to measure the
      segmentation result. The Acc of the proposed algorithm is 98.46 +/- 8.02E-03%,
      95.93 +/- 2.38E-02%, 93.88 +/- 6.59E-02%, 94.73 +/- 1.82E-01%, 96.19 +/- 1.15E
      02%, and 97.51 +/- 1.36E-02%, 96.64 +/- 6.35E-02%, and 94.76 +/- 6.21E-02%,
      respectively. The mean Mssim values of the 100 tests were 0.985, 0.933, 0.924,
      0.907, 0.984, 0.928, 0.938, and 0.941, respectively. Our proposed algorithm is
      more effective and robust in comparison to the other fuzzy entropy based on swarm
      intelligent optimization algorithms. The experimental results show that the
      proposed algorithm has higher accuracy in the segmentation of mammary glands, and
      may serve as a gold standard in the analysis of treatment of breast tumors.

PMID- 30203179
TI  - Peritoneal dialysis catheter placement, outcomes and complications.
AB  - PURPOSE: Peritoneal dialysis (PD) is a commonly used method for renal support in
      pediatric patients and can be associated with the risk of post-surgical
      complications. We evaluated method of placement of PD catheters with regard to
      post-surgical complications. METHODS: PD catheters placed at two institutions
      between 2005 and 2017 were reviewed. Complication rates were evaluated based on
      method of placement, delayed usage, omentectomy, and patient age using Fisher's
      exact test, two-sided, with significance set at 0.05. Factors influencing
      complication were evaluated with multivariate logistic regression and Kaplan
      Meier survival analysis. RESULTS: There were 130 patients with 157 catheters
      placed, ranging in age from 1 day to 23 years. There was no significant
      difference in complication rate by method of placement or delayed usage. Infants
      were significantly more likely to experience leakage (21% vs 8%, p 0.036) and
      hernias (15% vs 5%, p 0.030). Patients that underwent an omentectomy were less
      likely to require a catheter replacement (7% vs 27%, p 0.004), and the catheters
      had a significantly higher survival rate (p 0.009). We found that laparoscopic
      intervention resulted in catheter salvage. Lateral exit sites may be a risk
      factor for catheter migration in some patients. CONCLUSIONS: Omentectomy is
      associated with longer PD catheter survival. Laparoscopic salvage of
      dysfunctional catheters may be a valuable adjunct in management.

PMID- 30203181
TI  - Three dimensional gait analysis in patients with symptomatic component mal
      rotation after total knee arthroplasty.
AB  - PURPOSE: Purpose of the present cohort study was the determination of lower body
      function and rotation in patients with symptomatic component mal-rotation after
      total knee arthroplasty using instrumented 3D gait analysis. METHODS: A
      consecutive series of 12 patients (61.3 years +/- 11.4 years) were included
      suffering under remaining pain or limited range of motion at least six months
      after total knee arthroplasty. A CT-scan according to the protocol of Berger et
      al. and instrumented 3D gait analysis were carried out including clinical
      examination, videotaping, and kinematic analysis using a Plug-in Gait model.
      Outcome variables were temporospatial parameters as well as kinematics in
      sagittal and transversal plane. Data for reference group were collected
      retrospectively and matched by age and gender. RESULTS: Temporospatial parameters
      of the study group showed decreased velocity, cadence, and step length as well as
      increased step time. Single limb support was reduced for the affected limb. In
      sagittal plane, maximum knee flexion during swing phase was reduced for the
      replaced knee joint. In transverse plane, there was hardly any difference between
      affected and non-affected limb. Compared to the reference group, both limbs show
      significant increased internal ankle rotation and external hip rotation. There
      were significant strong linear correlations between ankle rotation and hip
      rotation as well as ankle rotation and radiological tibial mal-rotation.
      CONCLUSIONS: Patients with symptomatic component mal-rotation after total knee
      arthroplasty showed typically functional deficits. The affected and non-affected
      limb showed significant increased internal ankle rotation and external hip
      rotation, while only the affected, replaced knee showed reduced internal knee
      rotation. Identification of rotational abnormalities of hip and ankle joints
      seems to be mandatory in TKA to identify the patient group with external hip
      rotation, internal ankle rotation, and an elevated risk for symptomatic
      rotational TKA component mal-alignment.

PMID- 30203182
TI  - Quantification of shoulder muscle intramuscular fatty infiltration on T1-weighted
      MRI: a viable alternative to the Goutallier classification system.
AB  - BACKGROUND: Quantification of rotator cuff intramuscular fatty infiltration is
      important for clinical decision-making in patients with rotator cuff tear. The
      semi-quantitative Goutallier classification system is the most commonly used
      method, but has limited reliability. Therefore, we sought to test a freely
      available fuzzy C-means segmentation software program for reliability of the
      quantification of shoulder intramuscular fatty infiltration on T1-weighted MR
      images and for correlation with fat fraction by six-point Dixon MRI. MATERIALS
      AND METHODS: We performed a prospective cross-sectional study to measure visible
      intramuscular fat area percentage on oblique sagittal T1 MR images by fuzzy C
      means segmentation and fat fraction maps by six-point Dixon MRI for 42 shoulder
      muscles. Intra- and inter-observer reliability were determined. Correlative
      analysis for fuzzy C-means and six-point Dixon intramuscular fatty infiltration
      measures was also performed. RESULTS: We found that inter-observer reliability
      for the quantification of visible intramuscular fat area percentage by fuzzy C
      means segmentation and fat fraction by six-point Dixon MRI was 0.947 and 0.951
      respectively. The intra-observer reliability for the quantification of visible
      intramuscular fat area percentage by fuzzy C-means segmentation and fat fraction
      by six-point Dixon MRI was 0.871 and 0.979 respectively. We found a strong
      correlation between fuzzy C-means segmentation and six-point Dixon techniques; r
      = 0.850, p < 0.001 by individual muscle; and r = 0.977, p < 0.002 by study
      subject. CONCLUSION: Quantification of intramuscular fatty infiltration by fuzzy
      C-means segmentation on T1-weighted sequences demonstrates excellent reliability
      and strong correlation with fat fraction by six-point Dixon MRI. Quantitative
      fuzzy C-means segmentation is a viable alternative to the semi-quantitative
      Goutallier classification system.

PMID- 30203183
TI  - Extremity gossypiboma mimicking sarcoma: case report and review.
AB  - A 70-year-old man with a history of bladder and colon cancer presented with an
      enlarging mass in his right lower extremity. Forty years before presentation, he
      had injured his right lower extremity in a motor vehicle accident. Imaging
      findings indicated suspected sarcoma, which led to biopsy. Biopsy and further
      surgical exploration revealed the presence of a surgical sponge and surrounding
      local inflammatory reaction. No neoplasm was found, and the sponge and involved
      tissues were removed. Gossypiboma is exceedingly rare in the extremities. Imaging
      of retained foreign material can appear suggestive of sarcoma because of strong
      inflammatory responses and local tissue mass-like derangement resulting in
      heterogeneous signal changes. Ultimately, biopsy must be performed to ensure that
      no oncological pathological condition is present.

PMID- 30203180
TI  - The association between migraine and physical exercise.
AB  - BACKGROUND: There is an unmet need of pharmacological and non-pharmacological
      treatment options for migraine patients. Exercise can be used in the treatment of
      several pain conditions, including. However, what exact role exercise plays in
      migraine prevention is unclear. Here, we review the associations between physical
      exercise and migraine from an epidemiological, therapeutical and
      pathophysiological perspective. METHODS: The review was based on a primary
      literature search on the PubMed using the search terms "migraine and exercise".
      RESULTS: Low levels of physical exercise and high frequency of migraine has been
      reported in several large population-based studies. In experimental studies
      exercise has been reported as a trigger factor for migraine as well as migraine
      prophylaxis. Possible mechanisms for how exercise may trigger migraine attacks,
      include acute release of neuropeptides such as calcitonin gene-related peptide or
      alternation of hypocretin or lactate metabolism. Mechanisms for migraine
      prevention by exercise may include increased beta-endorphin, endocannabinoid and
      brain-derived neurotrophic factor levers in plasma after exercise. CONCLUSION: In
      conclusion, it seems that although exercise can trigger migraine attacks, regular
      exercise may have prophylactic effect on migraine frequency. This is most likely
      due to an altered migraine triggering threshold in persons who exercise
      regularly. However, the frequency and intensity of exercise that is required is
      still an open question, which should be addressed in future studies to delineate
      an evidence-based exercise program to prevent migraine in sufferers.

PMID- 30203184
TI  - Targeted Therapy and Immune Therapy for Small Cell Lung Cancer.
AB  - OPINION STATEMENT: Approximately 15% of the over 220,000 new lung cancers
      diagnosed each year in the USA are small cell lung cancer (SCLC). The standard of
      care for SCLC patients has not changed for many years. Therefore, there remains a
      need to evaluate novel drugs for the management of SCLC patients. In recent
      years, there is a greater understanding of the molecular alterations that occur
      in SCLC. There is an expectation that targeting these molecular alterations could
      provide clinical benefit. Targeting angiogenesis by inhibiting the vascular
      endothelial growth factor (VEGF) pathway has been evaluated in SCLC patients and
      has shown only limited clinical benefit. Alterations in DNA repair make these
      tumors susceptible to DNA repair pathway inhibitors and formed the basis for PARP
      inhibitor trials. Initial trials with PARP inhibitors have shown promising
      activity in some SCLC patients. Due to increased expression of anti-apoptotic Bcl
      2 proteins, drugs targeting these proteins may also provide clinical benefit. Pre
      clinical studies have shown that pathways of self-renewal such as the hedgehog
      and NOTCH pathways may be altered in SCLCs and could be targeted for therapeutic
      benefit. Initial trials with drugs targeting these pathways, including drugs
      targeting DLL3, a NOTCH ligand, suggest the need for appropriate biomarkers to
      identify SCLC patients most likely to benefit from these strategies. Trials of
      immune checkpoint inhibitors have shown that these agents may have therapeutic
      role in SCLC. As is true in other tumor types, these agents benefit only a
      proportion of patients but the benefit when observed can be sustained. Tumor
      mutational burden and PD-L1 expression may predict for clinical benefit with
      these agents. Ongoing trials will define the role of these agents in management
      of SCLC patients.

PMID- 30203185
TI  - Strongyloides stercoralis larvae found for the first time in tap water using a
      novel culture method.
AB  - Strongyloides stercoralis (S. stercoralis) is a soil-borne helminth but its
      prevalence in water samples is underestimated. The aim of the present study is to
      propose non-nutrient agar (NNA) as a novel culture method in the diagnosis of
      Strongyloides and to detect the prevalence rate of S. stercoralis larvae in tap
      water samples in Beni-Suef Governorate, Egypt. Eighty tap water samples were
      collected from Beni-Suef Governorate and each sample was filtered in three steps
      using three filters: one filter for microscopic examination of wet mount, while
      the remaining two filters were cultured on both NNA and nutrient agar plate
      (APC). S. stercoralis larvae, adults, and eggs were detected in two (2.5%) and
      four (5%) out of 80 samples after examination of wet mount preparation and
      cultures on both NNA and APC, respectively. NNA succeeded to maintain
      Strongyloides alive for up to 1 month. Our study is the first to detect
      Strongyloides larvae in tap water in Egypt and the first to use NNA as a novel
      culture media for Strongyloides.

PMID- 30203186
TI  - Gametogony of Eimeria cameli in the small intestine of one-humped camel (Camelus
      dromedarius).
AB  - Domesticated Old World camels (Camelus dromedarius and Camelus bactrianus) are
      important for the economy of several countries in Asia, Africa, and the Arabian
      Peninsula, and coccidiosis is an important disease in camels. There is confusion
      concerning the species of coccidian parasites in camels and their life cycles.
      Although five species of Eimeria (E. cameli, E. rajasthani, E. dromedarii, E.
      bactriani, and E. pellerdyi) were named from camels, E. cameli is considered the
      most pathogenic. Here, development of gametogonic stages and oocysts of E. cameli
      are described in the lamina propria of the small intestines of naturally infected
      camels. Only sexual stages have been confirmed.

PMID- 30203187
TI  - Mode of action of a novel anti-Listeria bacteriocin (CAMT2) produced by Bacillus
      amyloliquefaciens ZJHD3-06 from Epinephelus areolatus.
AB  - Bacteriocin CAMT2, produced by Bacillus amyloliquefaciens ZJHD3-06, has been
      shown to exhibit protective activity against important food spoilage and food
      borne bacterial pathogens. This study was conducted to investigate the mode of
      action of bacteriocin CAMT2 against highly pathogenic Listeria monocytogenes ATCC
      19111. The addition of bacteriocin CAMT2 at 64 AU/ml inhibited L. monocytogenes
      ATCC 19111. An efflux of K+ ions, lactic acid dehydrogenase and an increase in
      extracellular electrical conductivity was observed in CAMT2-treated L.
      monocytogenes. Electron microscopy showed morphological alterations such as
      uneven cell surface, accumulation of cell debris and bacterial lysis. These
      results show that bacteriocin CAMT2 inhibit L. monocytogenes by increasing cell
      permeability and inducing membrane damage, hence it has the great application
      potentials in ensuring food safety.

PMID- 30203188
TI  - Another interpretation of the Goldman-Hodgkin-Katz equation based on Ling's
      adsorption theory.
AB  - According to standard membrane theory, the generation of membrane potential is
      attributed to transmembrane ion transport. However, there have been a number of
      reports of membrane behavior in conflict with the membrane theory of cellular
      potential. Putting aside the membrane theory, we scrutinized the generation
      mechanism of membrane potential from the view of the long-dismissed adsorption
      theory of Ling. Ling's adsorption theory attributes the membrane potential
      generation to mobile ion adsorption. Although Ling's adsorption theory conflicts
      with the broadly accepted membrane theory, we found that it well reproduces
      experimentally observed membrane potential behavior. Our theoretical analysis
      finds that the potential formula based on the GHK eq., which is a fundamental
      concept of membrane theory, coincides with the potential formula based on Ling's
      adsorption theory. Reinterpreting the permeability coefficient in the GHK eq. as
      the association constant between the mobile ion and adsorption site, the GHK eq.
      turns into the potential formula from Ling's adsorption theory. We conclude that
      the membrane potential is generated by ion adsorption as Ling's adsorption theory
      states and that the membrane theory of cellular potential should be amended even
      if not discarded.

PMID- 30203189
TI  - Electric Field-Assisted In Situ Precise Deposition of Electrospun gamma
      Fe2O3/Polyurethane Nanofibers for Magnetic Hyperthermia.
AB  - A facial electrospinning method of in situ precise fabricating magnetic fibrous
      membrane composed of polyurethane (PU) nanofibers decorated with
      superparamagnetic gamma-Fe2O3 nanoparticles with simultaneous heat generation in
      response to alternating magnetic field (AMF) is reported. In this method, a
      conical aluminum auxiliary electrode is used to regulate the electrostatic field
      and affect the process of electrospinning for the in situ rapid and precise
      deposition of electrospun gamma-Fe2O3/PU fibers. The auxiliary conical electrode
      can extend the jet stabilization zone of the precursor solution four times longer
      than that of without auxiliary electrode, which can achieve the precise control
      of the fiber deposition area. Moreover, the electrospun composite fibrous
      membranes show a rapid temperature increase from room temperature to 43  degrees
      C in 70 s under the AMF, which exhibits faster heating rate and higher heating
      temperature compared to the samples fabricated without the assist of the
      auxiliary electrode. The present results demonstrate that the in situ precise
      electrospinning with the help of an auxiliary conical electrode has the potential
      as a manipulative method for preparing magnetic composite fibers as well as
      magnetic hyperthermia of cancer therapy.

PMID- 30203190
TI  - Cardiovascular magnetic resonance of cardiac morphology and function: impact of
      different strategies of contour drawing and indexing.
AB  - BACKGROUND: Cardiovascular magnetic resonance (CMR) is the gold standard for the
      quantitative assessment of cardiac volumes, mass and function. There are,
      however, various strategies for establishing endocardial borders, the cardiac
      phase used for measurements and the body dimensions used for indexing these
      results. The aim of the study was to assess the impact of different strategies on
      reference values. METHODS AND RESULTS: 362 healthy volunteers (190 men, mean age
      51 +/- 13 years) underwent a standard CMR protocol. Left ventricular end
      diastolic (LV-EDV) and end-systolic (LV-ESV) volumes and LV mass (LV-M) were
      measured at end systole and end diastole in SSFP sequences using two methods, one
      of which included papillary muscles and trabecular tissue in the LV-M ("include"
      approach), while the other excluded this tissue ("exclude" approach). There was a
      strong correlation between the results for LV volumes and LV ejection fraction
      (LV-EF) between the "include" and the "exclude" approach, while the mean values
      were different: LV-EDV: 149.7 +/- 32.5 ml vs 160.5 +/- 35.0 ml, p < 0.0001; LV
      ESV: 48.7 +/- 14.5 ml vs 56.4 +/- 16.7 ml, p < 0.0001; LV-EF: 67.7 +/- 5.4% vs
      65.1 +/- 5.6%, p < 0.0001. When comparing end-systolic with end-diastolic data,
      values for LV-M were significantly higher in end systole irrespective of whether
      papillary muscles and trabecular tissues were included or not. Furthermore, LV-M
      missed overweight-induced LV hypertrophy when indexed to body surface area (BSA)
      instead of height. CONCLUSION: Quantitative assessment of LV volumes and mass
      with inclusion of papillary muscles and trabeculae to myocardial mass resulted in
      significantly different values, while indexing to BSA and not height may miss LV
      hypertrophy in terms of overweight.

PMID- 30203191
TI  - Treating HIV-Positive/Non-AIDS Patients for Community-Acquired Pneumonia with
      ART.
AB  - PURPOSE OF REVIEW: This article reviews the most recent publications on community
      acquired pneumonia (CAP) in the HIV-infected population on antiretroviral therapy
      (ART), focusing on epidemiology, prognostic factors, etiology, and antimicrobial
      therapy. The data discussed here were mainly obtained from a non-systematic
      review using Medline and references from relevant articles. RECENT FINDINGS: CAP
      remains a major cause of morbidity and mortality among HIV-infected patients and
      incurs high health costs despite the introduction of ART. HIV-infected patients
      are generally known to be more susceptible to bacterial pneumonia. Streptococcus
      pneumoniae is the most frequently reported pathogen in HIV-infected patients on
      ART, who present a higher rate of bacteremia than non-HIV-infected patients.
      Several studies have also examined microbial etiology and prognostic factors of
      CAP in HIV-infected patients on ART. Despite the high rate of bacterial pneumonia
      in these patients, mortality rates are not higher than in patients without HIV
      infection.

PMID- 30203192
TI  - Needle-related pain and distress management during needle-related procedures in
      children with and without intellectual disability.
AB  - Children with intellectual disability frequently undergo needle-related
      procedures for diagnosis or treatment. Nevertheless, only a few studies deal with
      pain and distress management during the procedure in this population of children.
      This study aimed to investigate the number of anxiety and pain management
      techniques performed during needle procedure in children with intellectual
      disability (cases) compared to a population of children without intellectual
      disability (controls). This multicenter cohort study was performed from July 2016
      to January 2018 in the pediatric ward of four urban hospitals in Italy. Eligible
      subjects were children with and without intellectual disability, from 4 to 17
      years old, who needed venipuncture or intravenous cannulation for diagnosis or
      treatment. Use of topical anesthesia, distraction techniques, and physical or
      verbal comfort during procedures were recorded. Pain and anxiety scores were also
      recorded. Forty-seven cases and 94 controls were recruited. Three pain- and
      anxiety-relieving techniques were performed during the procedure in 12 (25%)
      cases and in 10 controls (11%); two techniques were performed in 23 (50%) cases
      and in 26 (28%) controls; 12 (25%) cases and 52 (55%) controls received only
      one.Conclusion: In this series, children with intellectual disability received
      significantly more relieving techniques, but experienced more pain and anxiety
      when compared to children without intellectual disability. What is Known: *
      Children with intellectual disability experience more episodes of pain than
      cognitively healthy ones, and almost 10% of these episodes are due to medical
      procedures. What is New: * Children with intellectual disability despite
      receiving more relieving techniques during a needle-related procedure experienced
      more pain and anxiety when compared to healthy children.

PMID- 30203194
TI  - Characterization of quinoa (Chenopodium quinoa) fermented by Rhizopus oligosporus
      and its bioactive properties.
AB  - Quinoa is a pseudocereal that contains high quality protein, minerals, vitamins,
      polyphenols, and phytosterols. In this study, quinoa was fermented by Rhizopus
      oligosporus (R. oligosporus) up to 5 days and the functional compounds (L
      carnitine, GABA, vanillic acid and gallic acid) were analyzed by LC/MS. The
      amounts of L-carnitine and GABA were 0.13 mg/kg and 540 mg/kg for nonfermented
      quinoa (NF), 3.15 mg/kg and 1040 mg/kg for fermented quinoa at 3 days (3F), and
      1.54 mg/kg and 810 mg/kg for fermented quinoa at 5 days (5F). The vanillic acid
      and gallic acid were 1.3 and 0.1 mg/kg for NF, 1.55 and 2.37 mg/kg for 3F, and
      1.83 and 0.84 mg/kg for 5F, respectively. Total phenolic contents and total
      flavonoids contents were 41 mg gallic acid (GAE)/kg and 13 mg quercetin
      equivalent (QE)/kg for NF, 74 mg GAE/kg and 16 mg QE/kg for 3F, and 80 mg GAE/kg
      and 19 mg QE/kg for 5F, respectively. Antioxidant activity (SC50) was 3.6 mg/mL
      for NF, 3.4 mg/mL for 3F, and 2.3 mg/mL for 5F. Nitric oxide production on
      RAW264.7 macrophages of fermented quinoa revealed 29% and 56% inhibition of
      nitric oxide production for NF and 5F, respectively. Therefore, fermented quinoa
      can be used as a healthy and valuable food product.

PMID- 30203195
TI  - Correction to: Update on Devices for Diastolic Dysfunction: Options for a No
      Option Condition?
AB  - In the original publication, the author name "Amit Gupta" was incorrectly spelled
      as "Ahmit Gupta". The original article has been corrected.

PMID- 30203196
TI  - Cysteine thiol oxidation on SIRT2 regulates inflammation in obese mice with
      sepsis.
AB  - Obesity increases morbidity and mortality in acute illnesses such as sepsis and
      septic shock. We showed previously that the early/hyper-inflammatory phase of
      sepsis is exaggerated in obese mice with sepsis; sirtuin 2 (SIRT2) modulates
      sepsis inflammation in obesity. Evidence suggests that obesity with sepsis is
      associated with increased oxidative stress. It is unknown whether exaggerated
      hyper-inflammation of obesity with sepsis modulates the SIRT2 function in return.
      We showed recently that SIRT6 oxidation during hyper-inflammation of sepsis
      modulates its glycolytic function. This study tested the hypothesis that
      increased oxidative stress and direct SIRT2 oxidation exaggerate hyper
      inflammation in obesity with sepsis. Using spleen and liver tissue from mice with
      diet-induced obesity (DIO) we studied oxidized vs. total SIRT2 expression during
      hyper- and hypo-inflammation of sepsis. To elucidate the mechanism of SIRT2
      oxidation (specific modifications of redox-sensitive cysteines) and its effect on
      inflammation, we performed site-directed mutations of redox-sensitive cysteines
      Cys221 and Cys224 on SIRT2 to serine (C221S and C224S), transfected HEK293 cells
      with mutants or WT SIRT2, and studied SIRT2 enzymatic activity and NFKBp65
      deacetylation. Finally, we studied the effect of SIRT2 mutation on LPS-induced
      inflammation using RAW 264.7 macrophages. In an inverse relationship, total SIRT2
      decreased while oxidized SIRT2 expression increased during hyper-inflammation and
      SIRT2 was unable to deacetylate NFKBp65 with increased oxidative stress of
      obesity with sepsis. Mechanistically, both the mutants (C221S and C224S) show
      decreased (1) SIRT2 enzymatic activity, (2) deacetylation of NFKBp65, and (3)
      anti-inflammatory activity in response to LPS vs. WT SIRT2. Direct oxidation
      modulates SIRT2 function during hyper-inflammatory phase of obesity with sepsis
      via redox sensitive cysteines.

PMID- 30203193
TI  - Validation of a self-reported instrument to assess work-related difficulties in
      patients with migraine: the HEADWORK questionnaire.
AB  - BACKGROUND: The degree to which work-related difficulties are recognized in
      headache research is poor and often carried out with inadequate information such
      as "reduced ability to work as usual", which do not capture at all the variety of
      difficulties and the factors that impact over them. The aim of this paper is to
      present the validation of the HEADWORK questionnaire, which addresses the amount
      and severity of difficulties in work-related tasks and the factors that impact
      over them. METHODS: We developed a set of items based on a previous literature
      review and patients' focus groups and tested it on a wide set of patients with
      episodic and chronic migraine attending eight different Italian headache centers.
      HEADWORK factor structure was assessed with exploratory and confirmatory factor
      analysis; internal consistency and construct validity were addressed as well.
      RESULTS: The validation sample (N = 373) was mostly composed of patients with
      episodic migraine without aura (64.3%) and of females (81%). Factor analysis
      retrieved two different scales: "Work-related difficulties", composed of eleven
      items which explain 67.1% of the total variance, and "Factors contributing to
      work difficulties", composed of six items which explain 52.1% of the total
      variance. Both HEADWORK subscales have good measurement properties, with higher
      scores being associated to higher disability, lower quality of life, lower
      productivity, higher headache frequency and pain intensity. CONCLUSIONS: HEADWORK
      is a 17-item, two-scale questionnaire addressing the impact of migraine on work
      related difficulties in terms of difficulties in general or specific skills, and
      the factors contributing to these difficulties, defined as negative impact on
      work tasks. It can be used to address disability weights for the purpose of
      calculating the burden of migraine, and to assess the balance between therapeutic
      and side effects of medication on productivity.

PMID- 30203197
TI  - The original Akagi line is the most reliable: a systematic review of landmarks
      for rotational alignment of the tibial component in TKA.
AB  - PURPOSE: There is no present consensus on the most reliable anatomical landmarks
      or axes for tibial rotational alignment in total knee arthroplasty (TKA). The
      goal was therefore to review the literature and compare accuracy and
      repeatability of different axes for tibial baseplate rotation in TKA. METHODS:
      Medline and Embase were searched for articles that reported accuracy in terms of
      error or discrepancy from the trans-epicondylar axes (TEA), and/or repeatability
      in terms of intraclass correlation coefficient, of one or more axes used for
      tibial baseplate rotation in TKA. Twenty-one articles met criteria, and their
      data were extracted and tabulated. RESULTS: The selected articles evaluated 15
      different axes, 13 for reliability, 12 for repeatability. The lowest errors or
      discrepancies from the projected TEA were reported for the original 'Akagi line'
      (posterior cruciate ligament posteriorly to medial border of tibial tuberosity),
      its variant using the sulcus of the tibial spines as anterior landmark, as well
      as the anterior tibial border and the curve-on-curve technique. The best inter
      observer repeatabilities were reported for 'Akagi line' variants that use the
      geometric centre of the tibial plateau posteriorly and the medial border of the
      tibial tuberosity, or the medial sixth of the patellar tendon anteriorly.
      Considering accuracy and repeatability simultaneously, only two axes were found
      to satisfy both criteria consistently: the original 'Akagi line' and the anterior
      tibial border. CONCLUSIONS: Because of the small number of studies found, the
      collected evidence remains insufficient to recommend reference axes for intra
      operative rotational alignment of the tibial baseplate in TKA. A combination of
      two or more anatomical landmarks or projected axes could be used to ensure
      adequate tibial baseplate rotation, while considering individual patient
      morphology and implant design to optimize knee kinematics and prevent prosthetic
      overhang. LEVEL OF EVIDENCE: Level IV, systematic review of level III and IV
      studies.

PMID- 30203198
TI  - Patellofemoral design enhancements reduce long-term complications of postero
      stabilized total knee arthroplasty.
AB  - PURPOSE: Few studies investigated whether trochlear and patellar design
      enhancements improve long-term outcomes of total knee arthroplasty (TKA). This
      study aimed to compare the long-term survival and complication rates of two
      consecutive generations of the same TKA system with identical tibiofemoral
      geometry, but different patellofemoral designs. METHODS: The authors retrieved
      the records of 93 patients (104 knees) operated with the HLS II system and 116
      patients (122 knees) operated with HLS Evolution system. Patients were evaluated
      preoperatively and at a minimum of 10 years noting all complications. Kaplan
      Meier (KM) survival was compared for two endpoints: (1) revision of all
      components and (2) revision of any component. RESULTS: From the HLS II series,
      the incidence of revision of all components was 6.4%, and of any component was
      9.8%. From the HLS Evolution series, the incidence of revision of all components
      was 4.1%, and of any component was 5.1%. Comparing the survival at equivalent
      follow-up of 14 years, considering revision of all components, the HLS II had
      higher survival than the HLS Evolution (98.9% vs 95.9%), while considering
      revision of any component, the HLS II had lower survival than the HLS Evolution
      (93.0% vs 94.9%). The differences in survival of the two implants were not
      significant, neither at equivalent follow-up of 14 years (n.s.), nor at maximum
      follow-up of each cohort (n.s.). The complication rate was higher for the HLS II
      series compared to the HLS Evolution (28% vs 12%, p = 0.009), but patellofemoral
      complications were not more frequent (8% vs 6%, n.s.). CONCLUSIONS: Though the
      differences in survival of the two implants were not significant, conflicting
      findings are observed due to partial revisions for patellar fractures (5 in the
      HLS II series and 1 in the HLS Evolution series) which could be related to
      patellofemoral design enhancements. This study highlights the importance of
      patello-femoral geometry, which is often overlooked in TKA. LEVEL OF EVIDENCE:
      Retrospective comparative study, Level III.

PMID- 30203199
TI  - Asymptomatic focal calcium pyrophosphate crystal deposition within partially
      failed repair tissue after matrix-assisted autologous chondrocyte implantation.
AB  - Possible failures of autologous chondrocyte implantation (ACI), a cell-based
      technique for articular cartilage repair, are not always clinically apparent and
      the underlying mechanisms largely remain unknown. This case report presents the
      first scenario in the literature highlighting an association of a medium-term
      partial failure of an advanced ACI procedure (matrix-assisted ACI) in the knee
      with focal asymptomatic calcium pyrophosphate deposition disease, a common
      inflammatory pyrophosphate arthropathy. The specific presence of CPPDs, resulting
      from increased biomechanical stresses in the repair tissue-cartilage and repair
      tissue-subchondral bone integration sites, together with the absence of cartilage
      regeneration was identified and possibly contributed to the partial failure.
      Level of evidence V.

PMID- 30203200
TI  - Laparoscopic liver resection of hepatocellular carcinoma located in unfavorable
      segments: a propensity score-matched analysis from the I Go MILS (Italian Group
      of Minimally Invasive Liver Surgery) Registry.
AB  - OBJECTIVE: Laparoscopic liver resection (LLR) for Hepatocellular Carcinoma (HCC)
      is one of the most important indications for the minimally invasive approach. Our
      study aims to analyze the experience of the Italian Group of Minimally Invasive
      Liver Surgery with laparoscopic surgical treatment of HCC, with a focus on tumor
      location and how it affects morbidity and mortality. METHODS: 38 centers
      participated in this study; 372 cases of LLR for HCC were prospectively enrolled.
      Patients were divided into two groups according to the HCC nodule location. Group
      1 favorable location and group 2 unfavorable location. Perioperative outcomes
      were compared between the two groups before and after a propensity score match
      (PS) 1:1. RESULTS: Before PS in group 2 surgical time was longer; conversion rate
      was higher; postoperative transfusion and comprehensive complication index were
      also higher. PS was performed with a cohort of 298 patients (from 18 centers),
      with 66 and 232 patients with HCC in unfavorable and favorable locations,
      respectively. After PS matching, 62 patients from group 1 and group 2 each were
      compared. Operative and postoperative course were similar in patients with HCC in
      favorable and unfavorable LLR locations. Surgical margins were found to be
      identical before and after PS. CONCLUSIONS: These results show that LLR in
      patients with HCC can be safely performed in all segments because of the
      extensive experience of all surgeons from multiple centers in performing
      traditional open liver surgery as well as laparoscopic surgery.

PMID- 30203201
TI  - Quantitative analysis of colon perfusion pattern using indocyanine green (ICG)
      angiography in laparoscopic colorectal surgery.
AB  - PURPOSE: This study aimed to quantitatively evaluate colon perfusion patterns
      using indocyanine green (ICG) angiography to find the most reliable predictive
      factor of anastomotic complications after laparoscopic colorectal surgery.
      METHODS: Laparoscopic fluorescence imaging was applied to colorectal cancer
      patients (n = 86) from July 2015 to December 2017. ICG (0.25 mg/kg) was slowly
      injected into peripheral blood vessels, and the fluorescence intensity of colonic
      flow was measured sequentially, producing perfusion graphs using a video analysis
      and modeling tool. Colon perfusion patterns were categorized as either fast,
      moderate, or slow based on their fluorescence slope, T1/2MAX and time ratio (TR =
      T1/2MAX/TMAX). Clinical factors and quantitative perfusion factors were analyzed
      to identify predictors for anastomotic complications. RESULTS: The mean age of
      patients was 65.4 years, and the male-to-female ratio was 63:23. Their operations
      were laparoscopic low anterior resection (55 cases) and anterior resection (31
      cases). The incidence of anastomotic complication was 7%, including colonic
      necrosis (n = 1), anastomotic leak (n = 3), delayed pelvic abscess (n = 1), and
      delayed anastomotic dehiscence (n = 1). Based on quantitative analysis, the
      fluorescence slope, T1/2MAX, and TR were related with anastomotic complications.
      The cut-off value of TR to categorize the perfusion pattern was determined to be
      0.6, as shown by ROC curve analysis (AUC 0.929, P < 0.001). Slow perfusion (TR >
      0.6) was independent factor for anastomotic complications in a logistic
      regression model (OR 130.84; 95% CI 6.45-2654.75; P = 0.002). Anastomotic
      complications were significantly correlated with the novel factor TR (> 0.6) as
      the most reliable predictor of perfusion and anastomotic complications.
      CONCLUSIONS: Quantitative analysis of ICG perfusion patterns using T1/2MAX and TR
      can be applied to detect segments with poor perfusion, thereby reducing
      anastomotic complications during laparoscopic colorectal surgery.

PMID- 30203202
TI  - Real-time diagnosis of Barrett's esophagus: a prospective, multicenter study
      comparing confocal laser endomicroscopy with conventional histology for the
      identification of intestinal metaplasia in new users.
AB  - INTRODUCTION: Endoscopic evaluation with high-definition white light endoscopy
      and random 4-quadrant biopsy (Seattle Protocol) is the current standard of care
      for the detection of Barrett's esophagus (BE). Recently, enhanced imaging
      technologies have become available to provide real-time diagnosis of intestinal
      metaplasia (IM) and dysplasia, reducing the need for tissue biopsy. Probe-based
      confocal laser endomicroscopy (pCLE) provides dynamic microscopic mucosal views,
      rapidly capturing digital images that become optical biopsies. This study
      examined the role of pCLE in BE screening and surveillance as compared to the
      Seattle Protocol. METHODS: Patients undergoing BE screening or surveillance
      endoscopy were enrolled at eight US centers. Optical biopsy using pCLE was
      interpreted in real time. Endoscopists performing pCLE were new users with a
      median experience of 8.5 months and no formal training in surgical pathology.
      Seattle Protocol biopsies were then taken. Recorded pCLE images were reviewed by
      a blinded expert in optical biopsy interpretation. RESULTS: Early pCLE users
      identified significantly more patients with IM than the Seattle Protocol overall
      (99/172 vs. 46/172, p < 0.0001). Early users of pCLE also identified
      significantly more patients with IM than the Seattle Protocol in the patients
      with visible columnar lined esophagus (75 vs. 31, p < 0.0001), but not in the 76
      patients without columnar lined esophagus (24 vs. 15, p = 0.067). There was no
      statistically significant difference between early pCLE users and expert review.
      CONCLUSION: Optical biopsy using pCLE technology allows for the real-time
      evaluation of entire segments of columnar lined esophagus. Consequently, pCLE is
      considerably more sensitive in the detection of BE than the Seattle Protocol,
      which leaves a majority of epithelium unexamined. This effect is seen even in new
      users and increases with experience. Overall, pCLE provides a promising advance
      in Barrett's detection which will likely result in superior identification of
      individuals at risk for esophageal adenocarcinoma.

PMID- 30203203
TI  - Intraoperative air leak test reduces the rate of postoperative anastomotic leak:
      analysis of 777 laparoscopic left-sided colon resections.
AB  - BACKGROUND: The evidence supporting the use of the air leak test (ALT) after
      laparoscopic left-sided colon resection (LLCR) to test the colorectal anastomosis
      (CA) integrity aiming at reducing the rate of postoperative CA leakage (CAL) is
      not conclusive. The aim of this study was to challenge the use of ALT after
      elective LLCR. METHODS: It is a retrospective analysis of a prospectively
      collected database including all patients undergoing elective LLCR with primary
      CA and no proximal bowel diversion between January 1996 and June 2017. The
      decision to perform the ALT was based on the individual surgeon routine practice.
      A multivariate analysis was performed to identify independent risk factors for
      CAL. RESULTS: A total of 777 LLCR without proximal diversion were included in the
      analysis: the CA was tested in 398 patients (ALT group), while intraoperative ALT
      was not performed in 379 patients (No-ALT group). The two groups were similar in
      demographic characteristics, indication, and type of procedure. Intraoperative
      ALT was positive in 20 (5%) patients: a stoma was created in 14 (70%) patients,
      while 6 (30%) patients had a suture repair alone. Overall, postoperative CAL
      occurred in 32 patients (4.1%): the postoperative CAL rate was lower in ALT
      patients (2.5% vs. 5.8%, p = 0.025). A reoperation was needed in 87.5% of cases.
      No CAL occurred in the 20 patients with intraoperative positive ALT. Multivariate
      analysis showed that ASA score 3-4 (OR 5.39, 95% CI 2.53-11.51, p < 0.001) and
      male sex (OR 3.96, 95% CI 1.66-9.43, p = 0.002) were independent risk factors for
      postoperative CAL, while intraoperative ALT independently reduced the
      postoperative CAL rate (OR 0.40, 95% CI 0.18-0.88, p = 0.022). CONCLUSION:
      Intraoperative ALT allows to detect AL defects after LLCR that can be effectively
      managed intraoperatively, leading to a significant lower risk of postoperative
      CAL.

PMID- 30203204
TI  - A comparison between one- and two-stage revisional gastric bypass.
AB  - BACKGROUND: The safety of performing a one-stage revision from laparoscopic
      adjustable gastric banding (LAGB) to laparoscopic Roux-en-Y gastric bypass
      (LRYGB) has been questioned. The objective of this study was to compare safety
      and outcomes of one-stage versus two-stage revisional LRYGB performed after
      failed LAGB. METHODS: A retrospective analysis of all patients undergoing
      revisional LRYGB after failed LAGB between January 2007 and March 2017 was
      performed. Patients undergoing one- and two-stage revisions were compared. The
      primary outcome assessed was the early complication rate, while secondary
      outcomes included late complications, weight loss, and improvement of
      comorbidities. RESULTS: During the study period, 161 revisional LRYGB's were
      performed, including 121 one-stage and 40 two-stage procedures. Baseline
      demographic data, BMI and presence of comorbidities were similar between the
      groups. In patients undergoing a two-stage procedure, band slippage, port
      infection, and erosion were more commonly cited as indications for revision.
      Similar early complication rates were demonstrated between the groups. However,
      late complications were more common in the two-stage group (20.0% vs. 7.4%, P =
      0.03), including higher rates of gastro-gastric fistula (5.0% vs. 0%, P = 0.01)
      and anemia (10.0% vs. 1.1%, P = 0.02). Three-fourths of the cohort had a follow
      up of more than 6 months, and the two groups demonstrated similar weight loss
      results and improvement/resolution of comorbidities. CONCLUSION: The performance
      of one-stage revisional LRYGB after failed LAGB seems to be a safe procedure,
      with noninferior outcomes when compared to a two-stage revisional procedure. It
      is a valid option, except in cases of mechanical and infectious band
      complications.

PMID- 30203205
TI  - Morbidity after transanal endoscopic microsurgery: risk factors for postoperative
      complications and the design of a 1-day surgery program.
AB  - BACKGROUND: Transanal endoscopic microsurgery (TEM) is a minimally invasive
      procedure with low morbidity. The definition of risk factors for postoperative
      complications would help to identify the patients likely to require more care and
      surveillance in an ambulatory or 1-day surgery (A-OdS) program. The main
      endpoints are overall 30-day morbidity and relevant morbidity. The secondary
      objectives are to detect risk factors for complications, rehospitalization, and
      the time of occurrence of the postoperative complications, and to describe the
      adverse effects following hospitalization that the A-OdS program would avoid.
      METHODS: This is an observational study of consecutive patients undergoing TEM
      between June 2004 and December 2016. Overall and relevant morbidity based on the
      Clavien-Dindo (Cl-D) classification were recorded, as were demographic,
      preoperative, surgical, and pathology variables. Univariate and multivariate
      analyses of the risk factors were carried out. RESULTS: Six hundred and ninety
      patients underwent surgery, of whom 639 were included in the study. Overall
      morbidity rate was 151/639 patients (23.6%); the clinically relevant morbidity
      rate was 36/639 (Cl-D > II) (5.6%) and mortality 2/639 (0.3%). The most frequent
      complication was rectal bleeding, recorded in 16.9% (108/639 patients) and grade
      I in 86/108 patients (78. 9%). The period with the greatest risk of complications
      was the first 2 days. The rehospitalization rate after 48 h was 7%. The risk
      factors for complications were as follows: tumor size > 6 cm (OR 3.2, 95% CI 1.3
      7.8), anti-platelet medication (OR 2.3, 95% CI 1.1-5.1), and surgeon's experience
      < 150 procedures (OR 2.0, 95% CI 1-4.1). CONCLUSIONS: TEM is a safe procedure.
      The low rates of morbidity, re-hospitalization, and postoperative complications
      in the first 2 days after surgery make the procedure suitable for A-OdS.

PMID- 30203206
TI  - A novel technique of pancreaticojejunostomy for laparoscopic
      pancreaticoduodenectomy.
AB  - BACKGROUND: Pancreaticojejunostomy (PJ) reconstruction is the Achilles' heel of
      laparoscopic pancreaticoduodenectomy (LPD). However, only a few studies have
      focused on the performance of this difficult procedure laparoscopically. METHODS:
      We present a safe and feasible technique of duct-to-mucosa pancreaticojejunostomy
      for LPD, named Bing's anastomosis. Our study included 238 cases of LPDs that
      underwent Bing's anastomosis. Data on the demographic characteristics, operative
      outcomes (total operative time, PJ duration, and estimated blood loss), and
      postoperative results (length of hospital stay, recovery of bowel function, and
      rates of postoperative morbidity and mortality) of the cases were prospectively
      collected and retrospectively analyzed. RESULTS: Only one patient (0.4%) in our
      series required conversion to open surgery as a result of uncontrolled bleeding
      from the superior mesenteric artery. The average operative time was 358 min (220
      min to 495 min). The mean duration for PJ was 23 min (19 min to 33 min). The mean
      estimated blood loss was 112 ml (50 ml to 800 ml). The overall incidence of
      pancreatic fistula was 21.4% and included 42 cases (17.6%) of biochemical leak,
      eight cases (3.4%) of Grade B, and one case (0.4%) of Grade C pancreatic
      fistulas. The 90-day mortality was 0.4%. CONCLUSIONS: Bing's anastomosis is a
      safe, reliable, and rapid PJ technique for LPD that is associated with favorable
      outcomes and a low risk of pancreatic fistula. However, its safety and
      feasibility should be verified by performing prospective randomized controlled
      trials at different institutions.

PMID- 30203207
TI  - Similar hematologic and nutritional outcomes after proximal gastrectomy with
      double-tract reconstruction in comparison to total gastrectomy for early upper
      gastric cancer.
AB  - BACKGROUND: Proximal gastrectomy offers theoretical benefits over total
      gastrectomy in terms of hematologic and nutritional outcomes. However, little
      evidence confirming these benefits has been reported. The aim of this study was
      to assess the hematologic and nutritional outcomes of proximal gastrectomy with
      double-tract reconstruction in comparison to those of total gastrectomy. METHODS:
      We retrospectively analyzed data from 80 patients with stage I gastric cancer who
      underwent proximal gastrectomy with double-tract reconstruction (n = 38) or total
      gastrectomy (n = 42) from September 2014 to December 2015. We compared
      hematologic (including hemoglobin, ferritin, vitamin B12, etc.) and nutritional
      outcomes [including body mass index (BMI), serum total protein, albumin, total
      cholesterol, and total lymphocyte count] between the two groups. RESULTS: We
      found no significant differences in changes in hemoglobin (P = 0.250) or
      cumulative incidence of iron deficiency anemia (P = 0.971) during a median follow
      up period of 24 months (range 18-30 months) after surgery. Cumulative incidence
      of vitamin B12 deficiency also did not differ significantly between the proximal
      and total gastrectomy groups (P = 0.087). BMI changes from baseline were not
      significantly different between the two groups (P = 0.591). Likewise, there were
      no statistically significant differences in nutritional outcomes. CONCLUSIONS:
      Proximal gastrectomy with double-tract reconstruction exhibited similar outcomes
      in terms of hematologic and nutritional features in comparison to total
      gastrectomy.

PMID- 30203208
TI  - Atypical cells in pathology of endobronchial ultrasound-guided transbronchial
      biopsy of peripheral pulmonary lesions: incidence and clinical significance.
AB  - BACKGROUND: Atypical cells may occasionally be the only pathologic finding in
      radial-probe endobronchial ultrasound (EBUS)-guided transbronchial biopsy (TBB)
      of peripheral pulmonary lesions (PPLs); however, it is uncertain how often we
      encounter such a situation and what clinical features can be used to identify
      these ambiguous PPLs, which are more likely to be malignant. METHODS: From 2009
      to 2016, consecutive patients referred for EBUS-guided TBB of PPLs and with
      pathology reports indicating atypical cells alone were included. Medical records
      were reviewed to extract patient demographics, clinical characteristics,
      procedural details and complications. The primary outcome was the final diagnosis
      of the PPLs on subsequent investigation. Multivariate logistic regression
      analysis was used to identify independent factors associated with a final
      malignant diagnosis. RESULTS: One hundred sixty-five (7.2%) of 2291 patients had
      non-diagnostic TBB showing atypical cells. Benign and malignant diagnoses were
      subsequently obtained in 45 (27%) and 120 (73%) patients, respectively. The
      leading malignancy was lung adenocarcinoma; of note, a variety of benign lesions
      revealed cellular atypia on pathology, in particular, chronic inflammation,
      tuberculosis and pneumonia. Multivariate analysis indicated lesion appearance
      [solid vs. others; odds ratio (OR) 7.93; 95% confidence interval (CI) 2.94-21.40;
      P < 0.001] and probe position (adjacent to vs. within; OR 3.36; 95% CI 1.11
      10.15; P = 0.032) were two significant factors predictive of a final diagnosis of
      malignancy. CONCLUSIONS: One out of 14 EBUS-guided TBB procedures for PPLs
      exhibited atypical cells on pathology. Meticulous management strategies should be
      formulated to deal with these instances after taking into consideration lesion
      appearance, probe position and patient preferences.

PMID- 30203209
TI  - Polyp size of 1 cm is insufficient to discriminate neoplastic and non-neoplastic
      gallbladder polyps.
AB  - BACKGROUND: A significant proportion of gallbladder polyps are non-neoplastic,
      for which resection is not necessary. However, international guidelines advocate
      cholecystectomy for all polyps >= 1 cm. This study assessed a national cohort of
      histopathologically proven gallbladder polyps to distinguish neoplastic from non
      neoplastic polyps. METHODS: PALGA, the nationwide network and registry of histo-
      and cytopathology, was searched to identify all histopathologically proven
      gallbladder polyps between 2003 and 2013. All polyps and (focal) wall thickenings
      > 5 mm were included, and classified as neoplastic or non-neoplastic. Polyp
      subtype, size, distribution, presentation as wall thickening or protruding polyp,
      and presence of gallstones were assessed for neoplastic and non-neoplastic
      polyps. A decision tree to distinguish neoplastic and non-neoplastic polyps was
      made and diagnostic accuracy of 1 cm surgical threshold was calculated. RESULTS:
      A total of 2085 out of 220,612 cholecystectomies contained a polyp (0.9%). Of
      these polyps, 56.4% were neoplastic (40.1% premalignant, 59.9% malignant) and
      43.6% non-neoplastic (41.5% cholesterol polyp, 37.0% adenomyomatosis, 21.5%
      other). Polyp size, distribution, and presence of gallstones were reported in
      1059, 1739 and 1143 pathology reports, respectively. Neoplastic polyps differed
      from non-neoplastic polyps in size (18.1 mm vs 7.5 mm, p < 0.001), singularity
      (88.2% vs 68.2%, p < 0.001), wall thickening (29.1% vs 15.6%, p < 0.001), and
      presence of gallstones (50.1% vs 40.4%, p = 0.001). However, adenomyomatosis
      presented with similar characteristics as neoplastic polyps. Fifty percent of
      polyps were >= 1 cm surgical threshold (optimal surgical threshold based on ROC
      curve); sensitivity for indicating neoplastic polyps was 68.1%, specificity was
      70.2%, and positive and negative predictive values were 72.9% and 65.1%.
      CONCLUSIONS: The prevalence of gallbladder polyps on cholecystectomy is low and
      many of the polyps are non-neoplastic. Clinicopathological characteristics differ
      between neoplastic and non-neoplastic polyps in general, but these cannot
      properly indicate neoplasia. The 1 cm surgical threshold has moderate diagnostic
      accuracy and is insufficient to indicate surgery for neoplastic gallbladder
      polyps.

PMID- 30203210
TI  - Meta-analysis of short- and long-term outcomes after pure laparoscopic versus
      open liver surgery in hepatocellular carcinoma patients.
AB  - BACKGROUND: The advantages of laparoscopy are widely known. Nevertheless, its
      legitimacy in liver surgery is often questioned because of the uncertain value
      associated with minimally invasive methods. Our main goal was to compare the
      outcomes of pure laparoscopic (LLR) and open liver resection (OLR) in patients
      with hepatocellular carcinoma. METHODS: We searched EMBASE, MEDLINE, Web of
      Science, and The Cochrane Library databases to find eligible studies. The most
      recent search was performed on December 1, 2017. Studies were regarded as
      suitable if they reported morbidity in patients undergoing LLR versus OLR.
      Extracted data were pooled and subsequently used in a meta-analysis with a random
      effects model. Clinical applicability of results was evaluated using predictive
      intervals. Review was reported following the PRISMA guidelines. RESULTS: From
      2085 articles, forty-three studies (N = 5100 patients) were included in the meta
      analysis. Our findings showed that LLR had lower overall morbidity than OLR
      (15.59% vs. 29.88%, p < 0.001). Moreover, major morbidity was reduced in the LLR
      group (3.78% vs. 8.69%, p < 0.001). There were no differences between groups in
      terms of mortality (1.58% vs. 2.96%, p = 0.05) and both 3- and 5-year overall
      survival (68.97% vs. 68.12%, p = 0.41) and disease-free survival (46.57% vs.
      44.84%, p = 0.46). CONCLUSIONS: The meta-analysis showed that LLR is beneficial
      in terms of overall morbidity and non-procedure-specific complications. That
      being said, these results are based on non-randomized trials. For these reasons,
      we are calling for randomization in upcoming studies. Systematic review
      registration: PROSPERO registration number CRD42018084576.

PMID- 30203211
TI  - Bisacodyl removal from contaminated solution by synthesized mesoporous silica
      using experimental design method.
AB  - Most of the medicinal compounds are entered no change into municipal wastewater
      and more than 90% of it remains in the wastewater. Mesoporous silica is known as
      thermally stable materials with controllable porosity and morphology. It is
      specified that these materials possess external and internal surfaces that can be
      selectively adsorbed the various compounds. In the present study, the synthesized
      mesoporous silica was studied to remove bisacodyl from polluted solutions.
      Mesoporous silica was synthesized by simple chemical method from
      tetraethylorthosilicate, ethanol (C2H5OH) and deionized water at 70  degrees C
      temperature. Characteristic of synthesized mesoporous silica was investigated by
      scanning electron microscopy. The effective parameters such as contact time, pH,
      adsorbate dose, and initial bisacodyl concentration were optimized for bisacodyl
      removal using 27 batch adsorption experiments according to design of experiment.
      The residual bisacodyl concentration was measured by UV-Vis spectrometer at the
      maximum wavelength of 580 nm. The statistical test and linear regression model
      were used by MINITAB 16 software for investigation of the main and interaction
      effects of each factor in the adsorption process. The ANOVA result showed 84% of
      bisacodyl was removed by synthesized mesoporous silica at optimum condition. The
      result of regression (R2 > 0.99) indicated that the adsorption process followed
      the Langmuir isotherm and second order kinetic at optimum conditions. The
      mesoporous silica is an efficient adsorbent for removing of bisacodyl from the
      polluted solutions so that it can be used for refining wastewaters containing
      medical compounds such as bisacodyl.

PMID- 30203212
TI  - [Ten key messages of the guidelines for family-centered care in intensive care
      medicine].
AB  - The family plays an important role in the care of the critically ill patient.
      There is a substantial psychological burden to family members during the
      intensive care management of the patient. The family has to bear the pitiable
      state of the patient with the feeling of helplessness. The critically ill patient
      is frequently unable to actively decide on the processes of intensive care.
      Therefore, the family has to take over the responsibility of representing the
      values and wishes of the patient and become involved in decision making, for
      which most family members are not prepared. A considerable proportion of family
      members suffers from stress, anxiety and depression. This psychological burden
      also continues after the conclusion of the intensive care management. Therefore,
      structured approaches are needed to support family members of critically ill
      patients during the intensive care management. In this short review, we present
      the ten key messages of the recent guidelines for family-centered care in the
      intensive care unit by the Society of Critical Care Medicine.

PMID- 30203215
TI  - A Reappraisal of Charles Darwin's Engagement with the Work of William Sharp
      Macleay.
AB  - Charles Darwin, in his species notebooks, engaged seriously with the quinarian
      system of William Sharp Macleay. Much of the attention given to this engagement
      has focused on Darwin's attempt to explain, in a transmutationist framework, the
      intricate patterns that characterized the quinarian system. Here, I show that
      Darwin's attempt to explain these quinarian patterns primarily occurred before he
      had read any work by Macleay. By the time Darwin began reading Macleay's
      writings, he had already arrived at a skeptical view of the reality of these
      patterns. What most interested Darwin, as he read Macleay, was not the quinarian
      system itself. Rather, Darwin's notes on his reading primarily concerned certain
      background principles animating Macleay's work, in particular: (a) the non
      existence of a saltus between human and animal minds, (b) the difficulty of
      establishing boundaries between species and varieties, and (c) Macleay's method
      of variation. Darwin's interest in the last of these left a mark on his
      discussion of taxonomic methodology in the Origin.

PMID- 30203213
TI  - Evaluating the Current Literature on Treatments Containing Adipose-Derived Stem
      Cells for Osteoarthritis: a Progress Update.
AB  - PURPOSE OF REVIEW: Recent studies have investigated the effect of treatments
      containing adipose-derived mesenchymal stem cells (ADMSCs) on human
      osteoarthritis. These have mostly used biologic adjuvants which may influence
      results. Thus, the purpose of this systematic review is to evaluate the current
      literature on these treatments when used in isolation. RECENT FINDINGS: Five
      studies in this review used cultured ADMSCs, while four studies used stromal
      vascular fraction and three used micro-fragmented adipose tissue to deliver
      ADMSCs. No studies reported serious treatment-related adverse effects and all
      reported improvements in clinical measures for at least one dose. This was not
      necessarily reflected in imaging evaluations nor were improvements always
      maintained. Current low-level evidence is limited due to variability in study
      methodology but indicates that treatments containing ADMSCs, when used in
      isolation, are safe and have the potential to reduce pain and improve function.
      Randomized controlled trials are now needed.

PMID- 30203216
TI  - [Report on the meeting of the working group on cardiac, vascular, renal, and
      transplantation pathology].

PMID- 30203217
TI  - [Minutes of the Working Group on Gynecopathology and Breast Pathology, 24 May
      2018 : 102nd Annual Congress of the German Society of Pathology].

PMID- 30203218
TI  - [Gunther Schubert : August 17, 1930-October 23, 2017].

PMID- 30203219
TI  - Hydrogeochemical characterization and evaluation of groundwater quality in
      Kangayam taluk, Tirupur district, Tamil Nadu, India, using GIS techniques.
AB  - The main objective of the present study is to evaluate the hydrogeochemical
      characteristics of groundwater and its suitability for drinking water supply in
      Kangayam taluk, Tirupur district, Tamil Nadu, India. To achieve this objective,
      seventy-eight groundwater samples were collected from the wells spread over the
      study area during December 2016. The collected groundwater samples were tested in
      the laboratory for various hydrogeochemical parameters such as hydrogen ion
      concentration (pH), electrical conductivity, total dissolved solids, total
      hardness, calcium, magnesium, sodium, potassium, chloride, bicarbonate,
      carbonate, nitrate, sulphate and fluoride. The analytical results were compared
      with WHO drinking water standards to assess the suitability of groundwater for
      drinking purposes. To understand the spatial variation of hydrogeochemical
      parameters over the study area, choropleth (zonation) maps were prepared using
      geographical information system (GIS). Overall groundwater quality zones were
      demarcated by overlaying and integrating all the spatial plots using GIS. Three
      groundwater quality zones such as (1) most desirable, (2) maximum allowable and
      (3) not permissible were demarcated based on the limits prescribed by the WHO for
      drinking purposes. This study indicates that 49% of the study area does not
      possess potable groundwater. About 21% of the area represents "most desirable"
      category, and the remaining 30% area represents "maximum allowable" category for
      drinking purposes. The Piper's trilinear diagram indicates that groundwater of
      this region is Mixed CaMgCl type. As the groundwater quality is poor nearly 49%
      of the total area, it is necessary to go for treatment before drinking water
      supply. It is also essential to recharge the aquifer artificially to improve the
      quantity and quality of groundwater.

PMID- 30203220
TI  - The sources and chemical content of edible soil sticks sold in markets in
      Tanzania: a cross-sectional analytical study.
AB  - Geophagy, or eating soil, is common in various countries including Tanzania.
      Studies have reported on the levels of different chemicals in consumed soil, some
      of which can be harmful to the health of individuals practicing geophagy. Dried
      soil sticks for eating, referred to as pemba, are commercially available in many
      markets in sub-Saharan Africa, but few studies have established the sources of
      the soils. The purpose of the current study was to: (1) systematically document
      the sources of the soils used in pemba commonly sold in regional markets
      throughout Tanzania using a global positioning system (GPS) to establish the
      supply chain flow of pemba to markets, and (2) assess the chemical element
      content of the soil sources for both water-extractable chemical element (WEC) and
      total chemical element (TC) contents. Surveys were conducted at regional markets
      across mainland Tanzania to identify the sources of soils commonly used in
      commercially available soil sticks. Then, soil samples were collected from
      identified sources in 12 regions across Tanzania and analyzed for WEC and TC
      content using an inductively coupled plasma mass spectrometry laboratory
      technique. Mining of the pemba soil was localized in 12 regions. Analysis of the
      supply chain flow revealed a well-established distribution network that ensured
      transportation and marketing of the soil sticks to regions throughout the
      country. WEC and TC of essential and trace elements (Ca, Fe, K, Mg, Na, Mn, Co,
      Cr, V, Mo, Cu, and Zn) and toxic elements (Al, As, Ba, Cd, Ni, and Pb) were
      detected at varying concentrations. Most of the trace and toxic elements were
      above the normal range, based on the oral maximum tolerable limits designated by
      the World Health Organization and US Agency for Toxic Substance and Disease
      Registry. This is the first study in Tanzania to document and examine the source
      soil locations for commercially available soil sticks at the macroscale across
      the entire country. The findings suggest that geophagy could be a significant
      exposure pathway for toxic elements.

PMID- 30203222
TI  - The Hazards of a Ubiquitary Metalloid, Arsenic, Hiding in Infant Diets:
      Detection, Speciation, Exposure, and Risk Assessment.
AB  - Different types of infant foods categorized as formulas, cereals, and purees
      imported from seven different countries and available on the Kuwaiti retail
      market were collected for arsenic analysis. The samples were analyzed both for
      total arsenic concentration using ICP-MS and for arsenic speciation using HPLC
      ICP-MS. Speciation is essential for food analysis because of the toxicity and
      carcinogenicity of inorganic arsenic species. There was a strong positive linear
      correlation between the total and inorganic arsenic levels in the tested infant
      foods at the 95% confidence level. Arsenic concentrations detected in this study
      were implemented to calculate the total daily intake of arsenic, where the
      calculated daily intake values were utilized to assess the potential health risks
      to infants incurred by consuming different infant foods by calculating three
      different assessment indices namely, hazard quotient (HQ), cancer risk (CR), and
      margin of exposure (MOE). Both the total arsenic content and the safety of the
      investigated infant foods were compared to the ones associated with 406 different
      infant food types from seven different countries reported in the literature. This
      study confirms that infants are exposed to arsenic via diet since rice-based
      infant food products contained elevated levels of arsenic; consequently,
      warranting careful attention to diet choices both to limit this exposure and to
      avert potentially hazardous adverse health effects to the infants.

PMID- 30203221
TI  - A cadaveric model to evaluate the effect of unloading the medial quadriceps on
      patellar tracking and patellofemoral joint pressure and stability.
AB  - BACKGROUND: Vastus Medialis Muscles (VMM) damage has been widely identified
      following patellar dislocation. Rehabilitation programmes have been suggested to
      strengthen the VMM and reduce clinical symptoms of pain and instability. This
      controlled laboratory study investigated the hypothesis that reduced Vastus
      Medialis Obliquus (VMO) and Vastus Medialis Longus (VML) muscle tension would
      alter patellar tracking, stability and PFJ contact pressures. METHODS: Nine fresh
      frozen dissected cadaveric knees were mounted in a rig with the quadriceps and
      iliotibial band loaded to 205 N. An optical tracking system measured joint
      kinematics and pressure sensitive film between the patella and trochlea measured
      PFJ contact pressures. Measurements were repeated for three conditions: 1. With
      all quadriceps heads and iliotibial band (ITB) loaded; 2. as 1, but with the VMO
      muscle unloaded and 3. as 1, but with the VMO and VML unloaded. Measurements were
      also repeated for the three conditions with a 10 N lateral displacement force
      applied to the patella. RESULTS: Reduction of VMM tension resulted in significant
      increases in lateral patellar tilt (2.8 degrees ) and translation (4 mm), with
      elevated lateral and reduced medial joint contact pressures from 0.48 to 0.14
      MPa, and reduced patellar stability (all p < 0.05). CONCLUSIONS: These findings
      provide basic scientific rationale to support the role of quadriceps
      strengthening to resist patellar lateral maltracking and rebalance the articular
      contact pressure away from the lateral facet in patients with normal
      patellofemoral joint anatomy.

PMID- 30203223
TI  - The Molecular Mechanisms of Protective Role of Se on the G0/G1 Phase Arrest
      Caused by AFB1 in Broiler's Thymocytes.
AB  - This research was designed to explore the protective effects of sodium selenite
      on G0/G1 phase arrest induced by AFB1 in thymocytes of broilers. Two hundred
      eighty-eight Cobb broilers were divided into control group, + Se group (0.4 mg/kg
      Se), AFB1 group (0.6 mg/kg AFB1), and AFB1 + Se group (0.6 mg/kg AFB1 + 0.4 mg/kg
      Se). The results revealed that 0.4 mg/kg Se supplement in diets could improve the
      AFB1-induced histological lesions in the thymus consisting of the more vacuoles
      and nuclear debris in thymic cortical area. The results of flow cytometric detect
      showed that 0.4 mg/kg Se relieved the G0/G1 phase arrest caused by AFB1 in
      thymocytes. The results of transcription levels of ATM, p53, p21, p27, p15, p16,
      CyclinD1, CyclinE, Cdk6, Cdk2, and PCNA genes by qRT-PC, and protein expression
      level of PCNA by immunohistochemistry demonstrated that 0.4 mg/kg Se could reduce
      the adverse effects of AFB1 on these parameters. In conclusion, Se could relieve
      AFB1-induced G0/G1 phase arrest by p15 (or p16)-CyclinD1/Cdk6, ATM-p53-p21
      CyclinE/Cdk2, p27-CyclinE/Cdk2 pathways.

PMID- 30203224
TI  - Gastrointestinal Absorption and Renal Excretion of Fluoride After Ingestion of a
      High-Fluoride Dentifrice.
AB  - This study aimed to evaluate the gastrointestinal absorption and renal excretion
      of fluoride after the ingestion of high-fluoride dentifrice. Twelve volunteers
      participated in this in vivo, crossover, and blinded study. In three experimental
      phases, the volunteers were randomly assigned to one of three treatment groups,
      who ingested either the following: distilled and deionized water (control),
      conventional dentifrice (1100 MUg/g), or high-fluoride dentifrice (5000 MUg/g).
      Both dentifrices contained fluoride in the form of NaF/SiO2. To determine the
      rate of fluoride absorption, non-stimulated saliva was collected for up to 120
      min after ingestion and the area under the curve of the salivary fluoride
      concentration was plotted as a function of time and the maximum concentration
      determined. All urine produced during the 24 h before and after ingestion was
      collected, and urinary excretion was calculated from the difference between the
      urinary fluoride concentrations in the two periods. A specific ion electrode
      coupled to an ion analyzer was used to measure fluoride concentrations.
      Statistical analysis was performed by ANOVA followed by Tukey's test with p set
      at 5%. All measured parameters were highest after the ingestion of the dentifrice
      with 5000 MUg/g (p < 0.001), confirming that this has an increased level of
      bioavailable fluoride compared with the conventional dentifrice. The high
      fluoride dentifrice increases the concentration of salivary fluoride, which may
      explain its greater anticaries effect. However, it poses a potential risk of
      causing dental fluorosis and so should not be used by children.

PMID- 30203225
TI  - Efficacy and safety of sofosbuvir-velpatasvir with or without ribavirin in HCV
      infected Japanese patients with decompensated cirrhosis: an open-label phase 3
      trial.
AB  - BACKGROUND: In Japan, hepatitis C virus (HCV)-infected patients with
      decompensated cirrhosis currently have no treatment options. In this Phase 3
      study, we evaluated sofosbuvir-velpatasvir with or without ribavirin for 12 weeks
      in patients with any HCV genotype and decompensated cirrhosis [Child-Pugh
      Turcotte (CPT) class B or C] in Japan. METHODS: Patients were randomized 1:1 to
      receive sofosbuvir-velpatasvir with or without ribavirin for 12 weeks.
      Randomization was stratified by CPT class and genotype. Sustained virologic
      response 12 weeks following completion of treatment (SVR12) was the primary
      efficacy endpoint. RESULTS: Of the 102 patients enrolled, 57% were treatment
      naive, 78% and 20% had genotype 1 and 2 HCV infection, respectively, and 77% and
      20% had CPT class B and C cirrhosis, respectively, at baseline. Overall, 61% of
      patients were female and the mean age was 66 years (range 41-83). SVR12 rates
      were 92% (47/51) in each group. Among patients who achieved SVR12, 26% had
      improved CPT class from baseline to posttreatment week 12. Most adverse events
      (AEs) were consistent with clinical sequelae of advanced liver disease or known
      toxicities of ribavirin. Four patients (8%) who received sofosbuvir-velpatasvir
      and seven (14%) who received sofosbuvir-velpatasvir plus ribavirin experienced a
      serious AE. The 3 deaths (bacterial sepsis, gastric varices hemorrhage,
      hepatocellular carcinoma) were attributed to liver disease progression.
      CONCLUSION: Sofosbuvir-velpatasvir for 12 weeks provides a highly effective and
      well-tolerated therapy for Japanese patients with HCV and decompensated
      cirrhosis. Ribavirin did not improve efficacy but increased toxicity.

PMID- 30203226
TI  - Perspectives on interferon-alpha in the treatment of polycythemia vera and
      related myeloproliferative neoplasms: minimal residual disease and cure?
AB  - The first clinical trials of the safety and efficacy of interferon-alpha2 (IFN
      alpha2) were performed about 30 years ago. Since then, several single-arm studies
      have convincingly demonstrated that IFN-alpha2 is a highly potent anti-cancer
      agent in several cancer types but unfortunately not being explored sufficiently
      due to a high toxicity profile when using non-pegylated IFN-alpha2 or high
      dosages or due to competitive drugs, that for clinicians at first glance might
      look more attractive. Within the hematological malignancies, IFN-alpha2 has only
      recently been revived in patients with the Philadelphia-negative
      myeloproliferative neoplasms-essential thrombocytosis, polycythemia vera, and
      myelofibrosis (MPNs)-and in patients with chronic myelogenous leukemia (CML) in
      combination with tyrosine kinase inhibitors. In this review, we tell the IFN
      story in MPNs from the very beginning in the 1980s up to 2018 and describe the
      perspectives for IFN-alpha2 treatment of MPNs in the future. The mechanisms of
      actions are discussed and the impact of chronic inflammation as the driving force
      for clonal expansion and disease progression in MPNs is discussed in the context
      of combination therapies with potent anti-inflammatory agents, such as the JAK1-2
      inhibitors (licensed only ruxolitinib) and statins as well. Interferon-alpha2
      being the cornerstone treatment in MPNs and having the potential of inducing
      minimal residual disease (MRD) with normalization of the bone marrow and low
      JAK2V617F allele burden, we believe that combination therapy with ruxolitinib may
      be even more efficacious and hopefully revert disease progression in many more
      patients to enter the path towards MRD. In patients with advanced and
      transforming disease towards leukemic transformation or having transformed to
      acute myeloid leukemia, "triple therapy" is proposed as a novel treatment
      modality to be tested in clinical trials combining IFN-alpha2, DNA
      hypomethylator, and ruxolitinib. The rationale for this "triple therapy" is
      given, including the fact that even in AML, IFN-alpha2 as monotherapy may revert
      disease progression. We envisage a new and bright future with many more patients
      with MPNs obtaining MRD on the above therapies. From this stage-and even before
      vaccination strategies may open a new horizon with cure being the goal for some
      patients.

PMID- 30203227
TI  - Inhibiting IDO pathways to treat cancer: lessons from the ECHO-301 trial and
      beyond.
AB  - With immunotherapy enjoying a rapid resurgence based on the achievement of
      durable remissions in some patients with agents that derepress immune function,
      commonly referred to as "checkpoint inhibitors," enormous attention developed
      around the IDO1 enzyme as a metabolic mediator of immune escape in cancer. In
      particular, outcomes of multiple phase 1/2 trials encouraged the idea that small
      molecule inhibitors of IDO1 may improve patient responses to anti-PD1 immune
      checkpoint therapy. However, recent results from ECHO-301, the first large phase
      3 trial to evaluate an IDO1-selective enzyme inhibitor (epacadostat) in
      combination with an anti-PD1 antibody (pembrolizumab) in advanced melanoma,
      showed no indication that epacadostat provided an increased benefit. Here we
      discuss several caveats associated with this failed trial. First is the
      uncertainty as to whether the target was adequately inhibited. In particular,
      there remains a lack of direct evidence regarding the degree of IDO1 inhibition
      within the tumor, and previous trial data suggest that sufficient drug exposure
      may not have been achieved at the dose tested in ECHO-301. Second, while there is
      a mechanistic rationale for the combination tested, the preclinical data were not
      particularly compelling. More efficacious combinations have been demonstrated
      with DNA damaging modalities which may therefore be a more attractive
      alternative. Third, as a highly selective IDO1 inhibitor, epacadostat was
      advanced aggressively despite preclinical genetic evidence of tumors bypassing
      IDO1 blockade. Indeed, a well-grounded literature starting in 2011 points to
      targeting strategies that account for both IDO and tryptophan 2,3-dioxygenase as
      more appealing directions to pursue, including dual inhibitors and inhibitors of
      nodal downstream effector pathways such as aryl hydrocarbon receptor blockade.
      Overall, the clinical readout from a single trial with significant limitations is
      by no means a definitive test for the field. While biomarker information yet to
      be gleaned from ECHO-301 may yet reveal useful information regarding IDO1 pathway
      drugs, better rationalized compounds and better rationalized trial designs will
      be important in the future to accurately gauge medical impact.

PMID- 30203228
TI  - Assessment of Gold Nanoparticles-Inhibited Cytochrome P450 3A4 Activity and
      Molecular Mechanisms Underlying Its Cellular Toxicity in Human Hepatocellular
      Carcinoma Cell Line C3A.
AB  - Interactions of the 40 and 80 nm gold nanoparticles (AuNP) functionalized with
      cationic branched polyethylenimine (BPEI), anionic lipoic acid (LA), or neutral
      polyethylene glycol (PEG) with human hepatocellular carcinoma (HCC) cell line C3A
      have been investigated in the absence and presence of human plasma protein corona
      (PC). All bare (no PC) AuNP besides 80 nm LA-AuNP were cytotoxic to C3A but PC
      attenuated their cytotoxicities. Time-dependent cellular uptake of AuNP increased
      besides 40 nm BPEI-AuNP but PC suppressed their uptakes besides 80 nm PEG-AuNP.
      Biphasic responses of oxidative/nitrosative stress by BPEI-AuNP occurred in C3A
      cells, whereas PEG-AuNP was a potent antioxidant. All bare AuNP inhibited
      cytochrome P450 (CYP) 3A4 activity irrespective of size and surface charge but PC
      recuperated its activity besides PEG-AuNP. The 40 nm PEG-AuNP-modulated gene
      expression was mainly involved in mitochondrial fatty acid beta-oxidation and to
      a less degree hepatic efflux/uptake transporters. These studies contribute to a
      better understanding of AuNP interaction with key biological processes and their
      underlying molecular mechanisms in HCC, which may be further implicated in the
      development of more effective therapeutic target in HCC treatment.

PMID- 30203230
TI  - Surgical Outcomes for Perihilar Cholangiocarcinoma with Vascular Invasion.
AB  - PURPOSE: To investigate short- and long-term surgical outcomes for patients with
      perihilar cholangiocarcinoma and vascular invasion. METHODS: Data from 249
      patients who underwent perihilar cholangiocarcinoma surgery between 2000 and 2016
      were retrospectively analyzed. Patient evaluations included short-term surgical
      outcomes following vascular resection and long-term outcomes in cases with
      histopathological vascular invasion. RESULTS: Mortality was 3.6% overall; 16% for
      hepatic artery resections, 5.4% for portal vein resections, and 1.7% in the
      absence of vascular resection (p = 0.029). No between-group differences were
      observed in the incidence of Clavien-Dindo grade >= 3 complications. The factors
      related to perioperative mortality were hepatic artery resection (odds ratio [OR]
      = 25.5), right trisectionectomy (OR = 13.0), and central bisectionectomy (OR =
      13.8). Multivariate analysis for overall survival identified several prognostic
      factors: carcinoembryonic antigen level >= 5 ng/mL (hazard ratio [HR] = 1.68),
      poor differentiation (HR = 2.39), distant metastasis (HR = 1.97), and R1 invasive
      resection (HR = 2.13). Five-year overall survival for patients with portal vein
      invasion and M0R0/1cis was 35.6%, significantly worse than the 53.4% for patients
      with no portal vein invasion and M0R/1cis but better than the 0% for patients
      with portal vein invasion and M1 or R1. Those with hepatic arterial invasion and
      M0R0/1cis were 24.7%, significantly worse than the 53.4% for patients with no
      hepatic arterial invasion and M0R0/1cis but significantly better than the 0% for
      patients with hepatic arterial invasion and M1 or R1. CONCLUSION: Short-term
      outcomes for patients with perihilar cholangiocarcinoma and undergoing vascular
      resection were poor compared to those without vascular resection. Long-term
      survival in R0M0 disease was more favorable; aggressive surgery is recommended.

PMID- 30203229
TI  - Binding free energies in the SAMPL6 octa-acid host-guest challenge calculated
      with MM and QM methods.
AB  - We have estimated free energies for the binding of eight carboxylate ligands to
      two variants of the octa-acid deep-cavity host in the SAMPL6 blind-test challenge
      (with or without endo methyl groups on the four upper-rim benzoate groups, OAM
      and OAH, respectively). We employed free-energy perturbation (FEP) for relative
      binding energies at the molecular mechanics (MM) and the combined quantum
      mechanical (QM) and MM (QM/MM) levels, the latter obtained with the reference
      potential approach with QM/MM sampling for the MM -> QM/MM FEP. The semiempirical
      QM method PM6-DH+ was employed for the ligand in the latter calculations.
      Moreover, binding free energies were also estimated from QM/MM optimised
      structures, combined with COSMO-RS estimates of the solvation energy and
      thermostatistical corrections from MM frequencies. They were performed at the PM6
      DH+ level of theory with the full host and guest molecule in the QM system (and
      also four water molecules in the geometry optimisations) for 10-20 snapshots from
      molecular dynamics simulations of the complex. Finally, the structure with the
      lowest free energy was recalculated using the dispersion-corrected density
      functional theory method TPSS-D3, for both the structure and the energy. The two
      FEP approaches gave similar results (PM6-DH+/MM slightly better for OAM), which
      were among the five submissions with the best performance in the challenge and
      gave the best results without any fit to data from the SAMPL5 challenge, with
      mean absolute deviations (MAD) of 2.4-5.2 kJ/mol and a correlation coefficient
      (R2) of 0.77-0.93. This is the first time QM/MM approaches give binding free
      energies that are competitive to those obtained with MM for the octa-acid host.
      The QM/MM-optimised structures gave somewhat worse performance (MAD = 3-8 kJ/mol
      and R2 = 0.1-0.9), but the results were improved compared to previous studies of
      this system with similar methods.

PMID- 30203231
TI  - Determinants of Rectal Cancer Patients' Decisions on Where to Receive Surgery: a
      Qualitative Analysis.
AB  - BACKGROUND: Current literature suggests surgeons who perform large volumes of
      rectal cancer resections achieve superior outcomes, but only about half of rectal
      cancer resections are performed by high-volume surgeons in comprehensive
      hospitals. Little is known about the considerations of patients with rectal
      cancer when deciding where to receive surgery. METHODS: A purposive sample of
      stage II/III rectal adenocarcinoma survivors diagnosed 2013-2015 were identified
      through the Iowa Cancer Registry and interviewed by telephone about factors
      influencing decisions on where to receive rectal cancer surgery. RESULTS: Fifteen
      survivors with an average age of 63 were interviewed: 60% were male, 53% resided
      in non-metropolitan areas, and 60% received surgery at low-volume facilities.
      Most patients considered surgeon volume and experience to be important
      determinants of outcomes, but few assessed it. Recommendation from a trusted
      source, usually a physician, appeared to be a main determinant of where patients
      received surgery. Patients who chose low-volume centers noted comfort and
      familiarity as important decision factors. CONCLUSION: Most rectal cancer
      patients in our sample relied on physician referrals to decide where to receive
      surgery. Interventions facilitating more informed decision-making by patients and
      referring providers may be warranted.

PMID- 30203232
TI  - Topical Selenium Sulfide for the Treatment of Hyperkeratosis.
AB  - Hyperkeratosis presents as thickened skin. It can be congenital or acquired.
      Typically, it affects the palms and soles; the distribution of epidermal
      involvement is either diffuse, focal, or punctate. Microscopically, the
      pathologic signature of hyperkeratosis is marked orthokeratosis of the stratum
      corneum. Topical treatments provide the mainstay of therapy for hyperkeratosis.
      These include keratolytics (such as urea, salicylic acid, and lactic acid) and
      retinoids; physical debridement, topical corticosteroids, and phototherapy (using
      topical psoralen and ultraviolet A phototherapy) are other local therapeutic
      modalities. Selenium is a non-metallic essential element; its water-insoluble
      salt, selenium sulfide, is an active ingredient that is used (in either a foam,
      lotion, or shampoo) to treat not only seborrheic dermatitis but also tinea
      versicolor. Three individuals with hyperkeratosis involving their palms and/or
      soles are described; the hyperkeratosis was successful treated with topical
      selenium sulfide in either a 2.5% lotion/shampoo or a 2.75% foam. The response to
      topical selenium sulfide was not only rapid but also complete and sustained; none
      of the patients experienced any adverse events secondary to the therapy. In
      conclusion, we recommend that topical selenium sulfide be added to the
      therapeutic armamentarium for congenital or acquired hyperkeratosis-particularly
      for those patients with involvement of their palms and soles.

PMID- 30203233
TI  - Gold-coated iron oxide nanoparticles trigger apoptosis in the process of thermo
      radiotherapy of U87-MG human glioma cells.
AB  - Recently, gold-coated iron oxide nanoparticles (Au@IONPs) have received a great
      deal of attention in cancer therapy. In this in vitro study we aimed to
      investigate the anti-cancer effects of Au@IONPs core-shell nanoparticles when
      applied in thermo-radiotherapy. Moreover, we investigated the level of apoptosis
      induced in U87-MG human glioma cells after receiving a combinatorial treatment
      regimen (Au@IONPs + hyperthermia + radiotherapy). Firstly, the Au@IONPs
      nanocomplex was prepared and characterized. Cytotoxicity of the nanoparticles
      (various concentrations; 4 h incubation time) was investigated on U87-MG cells
      and finally the concentrations of 10 and 15 ug/mL were selected for further
      studies. After incubation of the cells with nanoparticles, they received
      hyperthermia (43  degrees C; 1 h) and then were immediately exposed to 6 MV X-ray
      (2 and 4 Gy). Following the treatments, MTT assay was used to analyze cell
      viability and flow cytometry was used to determine the level of apoptosis in each
      treatment group. The results revealed that nanoparticles have no significant
      cytotoxicity at concentrations lower than 10 ug/mL. Also, we observed that
      nanoparticles are able to enhance the cytotoxic effect of hyperthermia and
      radiation. The major mode of cell death was apoptosis when nanoparticles,
      hyperthermia and radiation were concomitantly applied to cancer cells. In
      conclusion, Au@IONP nanoparticle can be considered as a good thermo-radio
      sensitizer which triggers significant levels of apoptosis in cancer therapy. In
      this in vitro study, we report the anti-cancer effects of gold-coated iron oxide
      nanoparticles (Au@IONPs) when applied in thermo-radiotherapy.

PMID- 30203235
TI  - [Shaping children's health in the community!]

PMID- 30203236
TI  - Novel 1,4-dihydropyridine induces apoptosis in human cancer cells through
      overexpression of Sirtuin1.
AB  - 1,4-Dihydropyridines (1,4-DHPs) are important as a class of heterocyclic
      compounds that exhibit wide range of biological actions. Many of its derivatives
      are already characterized as medicinally important drugs and used worldwide. In
      this study, we have screened some novel Hantzsch 1,4-DHP compounds using both in
      silico (QSAR and Pharmacophore) and in vitro (cytotoxic screening). 1,4-DHP
      showed selective cytotoxicity against five human cancerous cell lines; A375,
      A549, HeLa, HepG2 and SH-SY5Y but limited effect towards normal skin keratinocyte
      (HaCaT), lung fibroblast (WL-38) and healthy peripheral blood mononuclear cells.
      In A375 and HepG2 cells, one of the 1,4-DHP derivative (DHP-8) was found to
      inhibit cell proliferation, and simultaneously increased the apoptotic population
      as well as mitochondrial membrane depolarization. Furthermore, the mitochondrial
      signal was triggered with the activation of cleaved Caspase9, Caspase3 and PARP.
      The treatment with DHP-8 also increased the expression level of SIRT1,
      subsequently decreasing the level of pAKTser473 and survivin. Reduced pAKTser473
      expression led to decrease the phosphorylated inactive form of GSK3betaser9 and
      as a result, proteasomal degradation of Mcl-1 occurred in both the cell lines.
      Here, we suggest that the apoptotic effect of DHP-8 in A375 and HepG2 cells was
      mediated by AKT and survivin pathways through SIRT1 activation. The involvement
      of DHP-8 in SIRT1 activation was further verified by co-treatment of nicotinamide
      with DHP-8 in both A375 and HepG2 cells. Overall, this study emphasizes the
      possible potential and therapeutic role of DHP-8 in skin and liver cancer.

PMID- 30203234
TI  - Cellular and molecular characteristics of pollen abortion in chrysanthemum cv.
      Kingfisher.
AB  - KEY MESSAGE: Microspore degeneration at the tetrad stage is associated with
      tapetum degeneration retardation. Some genes and proteins related to cell
      senescence and death are the key factors for pollen abortion. Chrysanthemum
      (Chrysanthemum morifolium) is a major floriculture crop in the world, but pollen
      contamination is an urgent problem to be solved in chrysanthemum production. C.
      morifolium 'Kingfisher' is a chrysanthemum cultivar that does not contain any
      pollen in mature anthers, thus it is a very important material for developing
      chrysanthemum without pollen contamination. However, the mechanism of its pollen
      abortion remains unclear. In this study, the cellular and molecular mechanisms of
      'Kingfisher' pollen abortion were investigated using transmission electron
      microscopy, RNA sequencing, isobaric tags for relative and absolute quantitation,
      and bioinformatics. It was found that the meiosis of microspore mother cells was
      normal before the tetrad stage, the microspores began to degenerate at the tetrad
      stage, and no microspores were observed in the anthers after the tetrad stage. In
      addition, transcriptomic and proteomic analyses showed that some genes and
      proteins related to cell senescence and death were identified to be implicated in
      chrysanthemum pollen abortion. These results indicated that the tetrad stage was
      the main period of pollen abortion, and the genes and proteins related to cell
      senescence and death contributed to pollen abortion. These add to our
      understanding of chrysanthemum pollen abortion and will be helpful for
      development of flowers without pollen contamination in the future.

PMID- 30203237
TI  - Chest compression-associated injuries in cardiac arrest patients treated with
      manual chest compressions versus automated chest compression devices (LUCAS II) -
      a forensic autopsy-based comparison.
AB  - The aim of this autopsy study was to investigate chest-compression associated
      injuries to the trunk in out-of-hospital and in-hospital non-traumatic cardiac
      arrest patients treated with automated external chest compression devices (ACCD;
      all with LUCAS II devices) versus exclusive manual chest compressions (mCC). In
      this retrospective single-center study, all forensic autopsies between 2011 and
      2017 were included. Injuries following cardiopulmonary resuscitation (CPR) in
      patients treated with mCC or ACCD were investigated and statistically compared
      using a bivariate logistic regression. In the seven-year period with 4433
      autopsies, 614 were analyzed following CPR (mCC vs. ACCD: n = 501 vs. n = 113).
      The presence of any type of trunk injury was correlated with longer resuscitation
      intervals (30 +/- 15 vs. 44 +/- 25 min, p < 0.05). In comparison with mCC,
      treatment with ACCD led to more frequent skin emphysema (5 vs 0%, p = 0.012),
      pneumothorax (6 vs. 1%, p = 0.008), lung lesions (19 vs. 4%, p = 0.008),
      hemopericardium (3 vs 1%, p = 0.025) and liver lesions (10 vs. 1%, p = 0.001),
      all irrespective of confounding aspects. Higher age and longer CPR durations
      statistically influenced frequency of sternal and rib fractures (p < 0.001). The
      mean number of fractured ribs did not vary significantly between the groups (6 +/
      3 vs. 7 +/- 2, p = 0.09). In this cohort with unsuccessful CPR, chest
      compression-related injuries were more frequent following ACCD application than
      in the mCC group, but with only minutely increased odds ratios. The severity of
      injuries did not differ between the groups, and no iatrogenic injury was declared
      by the forensic pathologist as being fatal. In the clinical routine after
      successful return of spontaneous circulation a computed tomography scan for CPR
      associated injuries is recommended as soon as possible.

PMID- 30203238
TI  - Association of Patient Profile with Glycemic Control and Hypoglycemia with
      Insulin Glargine 300 U/mL in Type 2 Diabetes: A Post Hoc Patient-Level Meta
      Analysis.
AB  - AIMS: To examine the association of baseline patient characteristics with study
      outcomes in people with type 2 diabetes receiving insulin glargine 300 U/mL (Gla
      300) versus glargine 100 U/mL (Gla-100), over a 6-month period. METHODS: A post
      hoc patient-level meta-analysis using data from three multicenter, randomized,
      open-label, parallel-group, phase 3a studies of similar design, in people
      previously receiving either basal and prandial insulin, basal insulin + oral
      antihyperglycemic drugs, or no prior insulin (EDITION 1, 2 and 3, respectively).
      The endpoints, glycated hemoglobin (HbA1c), hypoglycemia, body weight change, and
      insulin dose were investigated by subgroups: age (< 65 and >= 65 years), body
      mass index (BMI; < 30 and >= 30 kg/m2), age at onset (< 40, 40-50, and > 50
      years), and diabetes duration (< 10 and >= 10 years). RESULTS: Reduction in HbA1c
      was comparable between insulins, regardless of subgroup. The lower risk of >= 1
      nocturnal (00:00-05:59 h) confirmed (<= 3.9 mmol/L [<= 70 mg/dL]) or severe
      hypoglycemic event with Gla-300 versus Gla-100 was also unaffected by participant
      characteristics. While heterogeneity of treatment effect between diabetes
      duration subgroups was seen for the risk of >= 1 confirmed (<= 3.9 mmol/L [<= 70
      mg/dL]) or severe hypoglycemic event at any time (24 h), treatment effect
      consistently favored Gla-300; no evidence of heterogeneity was observed for the
      other subgroups. Annualized rates of confirmed (<= 3.9 mmol/L [<= 70 mg/dL]) or
      severe hypoglycemia and body weight change were not influenced by participant
      characteristics; a similar pattern was observed with insulin dose. CONCLUSIONS:
      Comparable glycemic control was observed with Gla-300 versus Gla-100, with less
      hypoglycemia, regardless of age, BMI, age at onset or diabetes duration. FUNDING:
      Sanofi. Plain language summary available for this article.

PMID- 30203239
TI  - Development of 12 microsatellite markers for Bombina orientails based on RNA-Seq
      and their usefulness in population genetic diversity.
AB  - Bombina orientalis is widely used due to bombesin which isolated from its skin.
      But in recent years, the population of B. orientalis has become declining
      distinctly because of human activities, environmental pollution, drought climatic
      conditions and other factors. In order to provide the molecular basis for the
      proposal of biodiversity conservation, we report the development of 12
      microsatellite markers for B. orientalis based on RNA-Seq. We test polymorphism
      against in 48 B. orientalis individuals which randomly selected from 182
      individuals take advantage of polyacrylamide gel electrophoresis (PAGE). These
      markers will be useful in the research on the genetic diversity, population
      genetic structure and other studies. For B. orientalis, all of these loci showed
      polymorphism, and in line with the H-W equilibrium law. The number of alleles per
      locus ranged from 3 to 21. The observed and expected heterozygosities ranged from
      0.0118 to 0.7795 and from 0.1612 to 0.8703, respectively. The polymorphism
      information content ranged from 0.153 to 0.857. And the genetic diversity of B.
      orientalis in Lushui Rivers is significantly higher than that in the Maoer
      Mountains.

PMID- 30203240
TI  - De novo assembly of genome and development of polymorphic microsatellite loci in
      the blue swimming crab (Portunus pelagicus) using RAD approach.
AB  - The blue swimming crab (Portunus pelagicus) is a valuable marine fishery resource
      in Indo-West Pacific Ocean. So far, rare genetic resource of this species is
      available. In this report, the restriction-site associated DNA (RAD) approach was
      employed to mine the genomic information and identify molecular markers in P.
      pelagicus. A total of 0.82 Gbp clean data were generated from the genome of
      individual "X2A". De novo assembly produced 85,796 contigs with an average length
      of 339 bp. A total of 45,464 putative SNPs and 17,983 microsatellite loci were
      identified from the genomes of ten individuals. Furthermore, 31 pairs of primers
      were successfully designed, with 16 of them exhibiting polymorphism in a wild
      population. For these polymorphic loci, the expected and observed alleles per
      locus ranged from 1.064 to 7.314 and from 2 to 11, respectively. The expected and
      observed heterozygosity per locus ranged from 0.0615 to 0.819 and from 0.0626 to
      1.000, respectively. Nine loci showed high informative with polymorphism
      information content (PIC) > 0.5. Five loci significantly deviated from Hardy
      Weinberg equilibrium in the samples analyzed. No linkage disequilibrium was found
      among the 16 polymorphic microsatellite loci. This study provided massive genetic
      resource and polymorphic molecular markers that should be helpful for studies on
      conservation genetics, population dynamics and genetic diversity of P. pelagicus
      and related crab species.

PMID- 30203241
TI  - An efficient method for bacterial production and activity assessment of
      recombinant human insulin like growth factor 1.
AB  - Human insulin like growth factor 1 directs physiological roles in cellular
      proliferation and differentiation process. The protein is considered as an
      important therapeutic target with clinical significance. In this study, to avoid
      production of human insulin like growth factor 1 as inclusion body, the
      thioredoxin was used as a solubilizing fusion tag. The expression of fusion human
      insulin like growth factor 1 was carried out in E. coli Rosetta-gami by
      transformation of pET-32b contained functional elements. The evaluation of
      different conditions involving protein expression including IPTG concentration,
      temperature and post induction time showed that 0.1 mM IPTG at 34  degrees C for
      4 h was the optimum condition. The isolated fusion protein was purified using
      nickel affinity purification and digested by entrokinase to produce mature
      recombinant protein without any additional tag. The accuracy of produced
      recombinant protein was confirmed by western blot analysis. Biological activity
      of produced recombinant human insulin like growth factor 1 was determined by its
      proliferation effects on MCF-7 cells, expansion of bovine granulosa cells and
      activation of PI3K/Akt signaling pathway in these cells. The present study
      provides a simple and efficient method for high-level production of soluble,
      active recombinant human insulin like growth factor 1 in E. coli.

PMID- 30203242
TI  - Possible roles of glutamine synthetase in responding to environmental changes in
      a scleractinian coral.
AB  - Glutamine synthetase is an enzyme that plays an essential role in the metabolism
      of nitrogen by catalyzing the condensation of glutamate and ammonia to form
      glutamine. In this study, the activity and responses of glutamine synthetase
      towards environmental changes were investigated in the scleractinian coral
      Pocillopora damicornis. The identified glutamine synthetase (PdGS) was comprised
      of 362 amino acids and predicted to contain one Gln-synt_N and one Gln-synt_C
      domain. Expression of PdGS mRNA increased significantly after 12 h (1.28-fold, p
      < 0.05) of exposure to elevated ammonium, while glutamine synthetase activity
      increased significantly from 12 to 24 h, peaking at 12 h (54.80 U mg-1, p <
      0.05). The recombinant protein of the mature PdGS (rPdGS) was expressed in E.
      coli BL21, and its activities were detected under different temperature, pH and
      glufosinate levels. The highest levels of rPdGS activity were observed at 25 
      degrees C and pH 8 respectively, but decreased significantly at lower
      temperature, and higher or lower pH. Furthermore, the level of rPdGS activities
      was negatively correlated with the concentration of glufosinate, specifically
      decreasing at 10-5 mol L-1 glufosinate to be less than 50% (p < 0.05) of that in
      the blank. These results collectively suggest that PdGS, as a homologue of
      glutamine synthetase, was involved in the nitrogen assimilation in the
      scleractinian coral. Further, its physiological functions could be suppressed by
      high temperature, ocean acidification and residual glufosinate, which might
      further regulate the coral-zooxanthella symbiosis via the nitrogen metabolism in
      the scleractinian coral P. damicornis.

PMID- 30203244
TI  - [Factors influencing the referral of nursing home patients to the hospital].
AB  - INTRODUCTION: Hospitalisation may cause negative effects on elderly patients.
      Therefore, it is important that referral and admission of older nursing home
      patients is well-considered. The aim of this study is to investigate the factors
      that affect the decision making process. METHOD: Questionnaire survey among
      elderly care physicians and physicians following the elderly care physician
      training program. RESULTS: Of the 1,540 surveys, 200 were returned (response rate
      of 13%). Over 60% of the respondents had referred a nursing home patient to the
      hospital in the previous month. A stay at a geriatric rehabilitation ward,
      suspicion of a fracture, a good quality of life, a patient's or family's wish for
      referral, no treatment restrictions, and follow-up appointments in the hospital
      were factors which made referral to the hospital more likely according to the
      respondents. Medical specialist consultation and the in hospital presence of a
      physician specialised in geriatric care were considered to be important. Referral
      was less likely if a patient was diagnosed with dementia, had a low quality of
      life or had treatment restrictions. CONCLUSION: Both patient-related and non
      patient-related factors influence hospital referral of nursing home patients.
      Further research is needed to determine whether these different factors
      contribute to the different outcomes of a hospital admission, to facilitate
      proper decision-making for elderly care physicians.

PMID- 30203243
TI  - Expression of the human TRIM14 and its mutant form (P207L) promotes apoptosis in
      transgenic loaches.
AB  - The tripartite-motif (TRIM)14 protein, one of the TRIM family members, was shown
      to participate in the antiviral and antibacterial defence. Besides, it appears to
      play an essential role in the processes of oncogenesis. In some types of human
      tumour cells, TRIM14 has been shown to inhibit apoptosis, while in others-the
      overexpression of TRIM14 promotes apoptosis. However, whether TRIM14 mediates
      apoptosis in the normal cells remains unknown. In the present study, we
      investigated the possible participation of the human TRIM14 gene and its mutant
      form (620C > T) in the induction of apoptosis in the transgenic larvae loach
      Misgurnus fossilis L. We observed that the expression of both forms of TRIM14
      gene was accompanied by the increase of the frequency of pyknotic nuclei in fish
      embryos compared to control groups. Accordingly, using the TUNEL assay, the
      enhanced apoptosis was revealed upon expression of both forms of TRIM14 gene. The
      transcription of proapoptotic genes (bax, tp53, and casp9) was significantly
      increased in transgenic loaches expressing human wild-type TRIM14, but remained
      unchanged upon expression of its mutant form. In addition, the transcription of c
      myc was upregulated in transgenic loaches expressing both forms. Thus, it can be
      assumed that during embryonic development TRIM14 has a proapoptotic effect on the
      cells via the activation of c-myc, tp53, and bax genes. Apparently, the mutant
      TRIM14 directs apoptosis via c-myc by p53-independent mechanism.

PMID- 30203246
TI  - Developing Charcot-Marie-Tooth Disease Recognition System Using Bacterial
      Foraging Optimization Algorithm Based Spiking Neural Network.
AB  - In the developing technology Charcot-Marie-Tooth (CMT) disease is one of the
      teeth diseases which are occurred due to the genetic reason. The CMT disease
      affects the muscle tissue which reduces the progressive growth of the muscle. So,
      the CMT disease needs to be recognized carefully for eliminating the risk factors
      in the early stage. At the time of this process, the system handles the
      difficulties while performing feature extraction and classification part. So, the
      teeth images are processed by applying the normalization method which eliminates
      the salt and pepper noise from data. From that, modified group delay function
      along with Cepstral coefficient features are extracted with effective manner.
      After that Bacterial Foraging Optimization Algorithm based features are selected.
      Then the selected features are examined by applying the Bacterial Foraging
      Optimization Algorithm based spiking neural network which successfully recognizes
      the CMT disease. At that point the productivity of the framework is assessed with
      the assistance of exploratory outcomes.

PMID- 30203247
TI  - Hepatic inflammatory pseudotumor associated with primary biliary cholangitis and
      elevated alpha-fetoprotein lectin 3 fraction mimicking hepatocellular carcinoma.
AB  - BACKGROUND: Hepatic inflammatory pseudotumor (IPT) is a rare benign lesion.
      Because there is no specific laboratory marker or radiographic appearance, the
      majority of reported cases of hepatic IPT have been diagnosed after surgery or at
      autopsy. The etiology of hepatic IPT remains unclear but several mechanisms have
      been postulated such as infection or immune reaction. CASE PRESENTATION: A 79
      year-old woman had been seeing her family doctor for hypertension, and she had
      been diagnosed with liver dysfunction for about 10 years. She continued attending
      follow-ups because of her drinking habit. Two months before her visiting our
      institution, further elevation of hepatobiliary enzymes was noted, and abdominal
      ultrasonography showed a hepatic tumor 4 cm in diameter in the lateral segment,
      so she was referred to our hospital. Hepatocellular carcinoma (HCC) was suspected
      because alpha-fetoprotein (102 ng/ml) (AFP) and lectin 3 (L3) fraction (85.4%)
      were elevated and the appearance on enhanced computed tomography was not
      inconsistent with HCC. Thus, we performed laparoscopic hepatectomy. She recovered
      uneventfully and was discharged on postoperative day 7. Pathological diagnosis
      revealed that the tumor was hepatic IPT and that the background liver condition
      was primary biliary cholangitis (PBC). AFP and L3 fraction decreased to normal
      ranges after surgery. CONCLUSIONS: In 7 of 29 patients (24.1%) with reported
      cases of tumor markers in liver IPT, carbohydrate antigen 19-9 was elevated and
      AFP was elevated in 2 of 58 patients (3.4%). AFP is also frequently elevated in
      benign liver diseases such as hepatitis and liver cirrhosis, and L3 fraction has
      been used as a tumor marker for HCC with high specificity. To our knowledge, this
      is the first report of a case diagnosed with liver IPT in which AFP and L3
      fraction increased before surgery and decreased to the normal range after
      resection. This confirms the rarity of hepatic IPT associated with PBC and
      elevated AFP and L3 fraction.

PMID- 30203248
TI  - Correction to: Antithrombotic therapy after mitral valve repair: VKA or aspirin?
AB  - The original version of this article unfortunately contained a mistake in the
      author name. The co-author name should be Frederikus A. Klok instead of Frederik
      A. Klok. The original article has been corrected.

PMID- 30203249
TI  - Using Mendelian Randomization to Decipher Mechanisms of Bone Disease.
AB  - PURPOSE OF REVIEW: This review summarizes the basic principles of Mendelian
      randomization (MR) and provides evidence for the causal effect of multiple
      modifiable factors on bone outcomes. RECENT FINDINGS: Several studies using MR
      approach have provided support for the causal effect of obesity on bone mineral
      density (BMD). Strikingly, studies have failed to prove a causal association
      between elevated 25(OH) D concentrations and higher BMD in community-dwelling
      individuals. The MR approach has been successfully used to evaluate multiple
      factors related to bone mineral density variation and/or fracture risk. The MR
      approach avoids some of the classical observational study limitations and
      provides more robust causal evidence, ensuring bigger success of the clinical
      trials. The selection of interventions based on genetic evidence could have a
      substantial impact on clinical practice.

PMID- 30203250
TI  - Carbon Nanomaterials for Treating Osteoporotic Vertebral Fractures.
AB  - PURPOSE OF REVIEW: To identify the use of carbon nanomaterials in bone
      regeneration and present new data on the regenerative capacity of bone tissue in
      osteopenic rats treated with graphene nanoribbons (GNRs). RECENT FINDINGS: The
      results show that the physical and chemical properties of the nanomaterials are
      suitable for the fabrication of scaffolds intended for bone regeneration. The in
      vitro tests suggested a non-toxicity of the GNRs as well as improved
      biocompatibility and bone mineralization activity. Here, for the first time, we
      evaluated the potential of GNRs in remodeling and repairing bone defects in
      osteoporotic animal models in vivo. Interestingly, bone mineralization and the
      initiation of the remodeling cycle by osteoclasts/osteoblasts were observed after
      the implantation of GNRs, thus implying healthy bone remodeling when using GNRs.
      This study, therefore, has opened our perspectives and certainly calls for more
      attention to the use of carbon nanomaterials for a wide range of osteoporosis
      applications.

PMID- 30203252
TI  - Risk of Adverse Drug Events Observed with Baricitinib 2 mg Versus Baricitinib 4
      mg Once Daily for the Treatment of Rheumatoid Arthritis: A Systematic Review and
      Meta-Analysis of Randomized Controlled Trials.
AB  - BACKGROUND: On 23 April 2018, the Food and Drug Administration-based Advisory
      Committee approved the use of baricitinib 2 mg for the treatment of rheumatoid
      arthritis and suggested the possibility of serious adverse events associated with
      baricitinib 4 mg. Hence, we aimed to systematically compare the risk of adverse
      drug events observed with baricitinib 2 mg versus 4 mg for the treatment of
      patients with rheumatoid arthritis. METHODS: Electronic databases including the
      Cochrane library, MEDLINE, EMBASE and http://www.ClinicalTrials.gov were searched
      for relevant English publications until April 2018. Adverse drug events at 12
      weeks and 24 weeks were considered as the clinical endpoints. RevMan 5.3 software
      was used to analyze the data whereby risk ratios (RR) and 95% confidence
      intervals (CI) were calculated. RESULTS: Four trials consisting of a total of 959
      participants were included in this analysis. At 12 weeks, no significant
      difference was observed between 2 mg and 4 mg baricitinib for serious adverse
      events (RR 1.33; 95% CI 0.63-2.78; p = 0.46), any adverse events after the start
      of therapy (RR 1.09; 95% CI 0.98-1.21; p = 0.13), discontinuation of drugs due to
      adverse events (RR 1.19; 95% CI 0.61-2.34; p = 0.60), malignancies (RR 3.03; 95%
      CI 0.12-73.90; p = 0.50), and major adverse cardiac events (RR 2.95; 95% CI 0.12
      71.91; p = 0.51). Infections including herpes zoster infections and serious
      infections were also similarly manifested. At 24 weeks, serious adverse events
      (RR 1.84; 95% CI 1.02-3.30; p = 0.04) were significantly higher with baricitinib
      4 mg compared with the 2-mg dosage. However, total adverse events after the start
      of therapy, discontinuation of drug due to adverse events, malignancies, major
      adverse cardiac events, infections including herpes zoster, and serious
      infections were not significantly different between the two doses. CONCLUSIONS:
      No significant differences in adverse drug events were observed between
      baricitinib 2 mg and 4 mg at 12 weeks' follow-up. However, this analysis showed
      the risk of serious adverse events to be significantly higher with baricitinib 4
      mg compared with baricitinib 2 mg at 24 weeks' follow-up. This hypothesis should
      be confirmed in larger trials with longer follow-up time periods.

PMID- 30203251
TI  - Osteoblastic Factors in Prostate Cancer Bone Metastasis.
AB  - PURPOSE OF REVIEW: Prostate cancer bone metastasis is the lethal progression of
      the disease. The disease frequently presents with osteoblastic lesions in bone.
      The tumor-induced bone can cause complications that significantly hamper the
      quality of life of patients. A better understanding of how prostate cancer
      induces aberrant bone formation and how the aberrant bone affects the progression
      and treatment of the disease may improve the therapies for this disease. RECENT
      FINDINGS: Prostate cancer-induced bone was shown to enhance tumor growth and
      confer therapeutic resistance in bone metastasis. Clinically, Radium-223, an
      alpha emitter that selectively targets bone, was shown to improve overall
      survival in patients, supporting a role of tumor-induced bone in prostate cancer
      progression in bone. Recently, it was discovered that PCa-induced aberrant bone
      formation is due, in part, from tumor-associated endothelial cells that were
      converted into osteoblasts through endothelial-to-osteoblast (EC-to-OSB)
      conversion by tumor-secreted BMP4. The unique bone-forming phenotype of prostate
      cancer bone metastasis plays a role in prostate cancer progression in bone and
      therapy resistance. Therapies that incorporate targeting the tumor-induced
      osteoblasts or EC-to-OSB conversion mechanism may reduce tumor-induced bone
      formation and improve therapy outcomes.

PMID- 30203253
TI  - Tumor long-axis diameter and SUVmax predict long-term responders in 90Y
      ibritumomab tiuxetan monotherapy.
AB  - 90Y-ibritumomab tiuxetan (90Y-IT) is widely used, but the factors responsible for
      its optimal treatment effects are unknown. We enrolled 34 patients with relapsed
      indolent lymphoma treated with 90Y-IT monotherapy at Gunma University Hospital
      between 2003 and 2014 in the present study. Clinical data including computed
      tomography and 18-Fluoro-deoxyglucose positron emission tomography were
      retrospectively analyzed. The overall response rate and complete response rate
      were 91% and 82%, respectively. The median progression-free survival (PFS) and
      overall survival were 32 months and not reached, respectively. In univariate
      analysis, tumor long-axis diameter <= 2.5 cm, maximum standardized uptake value
      (SUVmax) <= 6.5, localized disease, normal levels of serum soluble interleukin-2
      receptor, and the number of involved nodal sites <= 3 immediately prior to 90Y-IT
      were associated with median PFS greater than 6 years. However, in multivariate
      analysis, only tumor long-axis diameter <= 2.5 cm and SUVmax <= 6.5 affected PFS
      [hazard ratio (HR) 0.130, P = 0.0021 and HR 0.283, P = 0.0311, respectively].
      Patients with only one prior regimen needed less granulocyte colony-stimulating
      factor and platelet transfusion. Thus, 90Y-IT treatment should be considered for
      patients with indolent lymphoma in first relapse who have tumor long-axis
      diameter <= 2.5 cm and SUVmax <= 6.5.

PMID- 30203254
TI  - Identification of the copy number variant biomarkers for breast cancer subtypes.
AB  - Breast cancer is a common and threatening malignant disease with multiple
      biological and clinical subtypes. It can be categorized into subtypes of luminal
      A, luminal B, Her2 positive, and basal-like. Copy number variants (CNVs) have
      been reported to be a potential and even better biomarker for cancer diagnosis
      than mRNA biomarkers, because it is considerably more stable and robust than gene
      expression. Thus, it is meaningful to detect CNVs of different cancers. To
      identify the CNV biomarker for breast cancer subtypes, we integrated the CNV data
      of more than 2000 samples from two large breast cancer databases, METABRIC and
      The Cancer Genome Atlas (TCGA). A Monte Carlo feature selection-based and
      incremental feature selection-based computational method was proposed and tested
      to identify the distinctive core CNVs in different breast cancer subtypes. We
      identified the CNV genes that may contribute to breast cancer tumorigenesis as
      well as built a set of quantitative distinctive rules for recognition of the
      breast cancer subtypes. The tenfold cross-validation Matthew's correlation
      coefficient (MCC) on METABRIC training set and the independent test on TCGA
      dataset were 0.515 and 0.492, respectively. The CNVs of PGAP3, GRB7, MIR4728,
      PNMT, STARD3, TCAP and ERBB2 were important for the accurate diagnosis of breast
      cancer subtypes. The findings reported in this study may further uncover the
      difference between different breast cancer subtypes and improve the diagnosis
      accuracy.

PMID- 30203256
TI  - Abstracts for the Ninth American Conference on Pharmacometrics (ACoP9).

PMID- 30203255
TI  - Incorporation of Nanostructured Carbon Composite Materials into Counter
      Electrodes for Highly Efficient Dye-Sensitized Solar Cells.
AB  - Dye-sensitized solar cells (DSSCs) composed of nanostructured carbon composite
      materials-stacked counter electrodes (CEs) were fabricated in the present study.
      As the potential replacement of expensive platinum (Pt) thin film, various carbon
      composite materials, including zero-dimensional carbon nanoparticles (CNPs), one
      dimensional multiwalled carbon nanotubes (MWCNTs), and two-dimensional graphene
      flakes (GFs) as a suitable charge transfer medium were deposited on the surface
      of CEs using a screen printing process. As the results, CNPs were found to result
      in deteriorating the charge transfer from CE to liquid electrolyte due to the
      formation of highly aggregated structures with very low specific surface area.
      However, MWCNTs and MWCNTs-added carbon composites (e.g., CNP/MWCNT, MWCNT/GF,
      CNP/MWCNT/GF) were found to enhance the charge transfer from CE to liquid
      electrolyte due to the formation of highly networked structures with high
      specific surface area. The resulting PCE of DSSCs composed of pure MWCNTs- and
      MWCNTs-added carbon composites-based CEs were very similar with that of DSSCs
      composed of Pt-based CEs. This suggests that the nanostructured carbon materials
      especially composed of MWCNTs and their composites are one of the promising
      candidates to replace the expensive Pt in the CEs of DSSCs.

PMID- 30203260
TI  - Grey Matter Volumes in the Executive Attention System Predict Individual
      Differences in Effortful Control in Young Adults.
AB  - Effortful control (EC), considered as one component of temperament, describes an
      individual's capacity for self-regulation. Previous neuroimaging studies have
      provided convergent evidence that individual differences in EC are determined by
      the functioning of neural systems subserving executive attention, primarily
      comprising the anterior cingulate cortex (ACC) and the lateral prefrontal cortex
      (PFC). Notwithstanding, as previous neuroimaging findings highlighted the
      structural neural bases of EC in adolescence, during which the PFC is prominently
      remodeled, the underlying neuroanatomical substrates of EC remain uncertain in
      young adults. In this study, we included 246 healthy young adults and used voxel
      based morphometry analysis to investigate the relationship between EC and grey
      matter (GM) volumes. Additionally, permutation testing and cross-validation were
      applied to determine whether GM volumes in the detected regions could predict
      individual differences in EC. Our results revealed that EC was associated with GM
      volumes in the dorsal anterior cingulate cortex (dACC) and the pre-supplementary
      motor area (pre-SMA), demonstrating that these two regions may play a crucial
      role in EC. Furthermore, the identified regional GM volumes reliably contribute
      to the prediction of EC confirmed by cross-validation. Overall, these findings
      provide further evidence for the involvement of the executive attention system in
      EC, and shed more light on the neuroanatomical substrates of EC in young
      adulthood.

PMID- 30203261
TI  - Building a Cardio-Onco-Hematology Program.
AB  - PURPOSE OF REVIEW: This review aims to outline the general principles of how to
      build a cardio-onco-hematology clinic, acknowledging that there are diverse
      practices ranging from private community settings to academic hospitals and each
      practice environment has to build its own program. RECENT FINDINGS: The
      refinement of regimens and introduction of molecularly directed therapies have
      substantially increased survival rates for patients with cancer. In fact, a
      number of previous imminently fatal malignant disease processes have been turned
      into chronic diseases, such that patients now live with certain incurable cancers
      as they do, for instance, with rheumatoid arthritis. Improved cure rates and
      longer survivals have raised side effects of cancer treatments to a completely
      new level of significance. Cardiovascular toxicities are of particular concern
      given their impact on morbidity and mortality. In most extreme cases, patients
      might be cured from cancer but remain debilitated or die prematurely because of
      cardiovascular disease. Furthermore, not an insignificant proportion of cancer
      patients start cancer therapy with cardiovascular risk factors and diseases at
      baseline. With the aging of the population, this "joint venture" is only expected
      to increase with important implications for the management of cancer patients.
      Given the need for familiarity with both, cancer and cardiovascular diseases and
      their ever-evolving start-of-the-art therapy and interaction potential,
      specialized efforts have been invoked, which may collectively be termed "onco
      cardiology," "cardio-oncology," or "cardio-onco-hematology." Herein, we provide
      recommendations for the creation and optimization of any such programmatic
      efforts.

PMID- 30203262
TI  - Oncogenic MYD88 mutations in lymphoma: novel insights and therapeutic
      possibilities.
AB  - Oncogenic MYD88 mutations, most notably the Leu 265 Pro (L265P) mutation, were
      recently identified as potential driver mutations in various B-cell non-Hodgkin
      Lymphomas (NHLs). The L265P mutation is now thought to be common to virtually all
      NHLs and occurs in between 4 and 90% of cases, depending on the entity. Since it
      is tumor-specific, the mutation, and the pathways it regulates, might serve as
      advantageous therapeutic targets for both conventional chemotherapeutic
      intervention, as well as immunotherapeutic strategies. Here, we review recent
      progress on elucidating the molecular and cellular processes affected by the
      L265P mutation of MYD88, describe a new in vivo model for MyD88 L265P-mediated
      oncogenesis, and summarize how these findings could be exploited therapeutically
      by specific targeting of signaling pathways. In addition, we summarize current
      and explore future possibilities for conceivable immunotherapeutic approaches,
      such as L265P-derived peptide vaccination, adoptive transfer of L265P-restricted
      T cells, and use of T-cell receptor-engineered T cells. With clinical trials
      regarding their efficacy rapidly expanding to NHLs, we also discuss potential
      combinations of immune checkpoint inhibitors with the described targeted
      chemotherapies of L265P signaling networks, and/or with the above immunological
      approaches as potential ways of targeting MYD88-mutated lymphomas in the future.

PMID- 30203263
TI  - Persistent Lin28 Expression Impairs Neurite Outgrowth and Cognitive Function in
      the Developing Mouse Neocortex.
AB  - Many neurodevelopmental disorders feature learning and memory difficulties.
      Regulation of neurite outgrowth during development is critical for neural
      plasticity and memory function. Here, we show a novel regulator of neurite
      outgrowth during cortical neurogenesis, Lin28, which is an RNA-binding protein.
      Persistent Lin28 upregulation by in utero electroporation at E14.5 resulted in
      neurite underdevelopment during cortical neurogenesis. We also showed that Lin28
      overexpressing cells had an attenuated response to excitatory inputs and altered
      membrane properties including higher input resistance, slower action potential
      repolarization, and smaller hyperpolarization-activated cation currents,
      supporting impaired neuronal functionality in Lin28-electroporated mice. When we
      ameliorated perturbed Lin28 expression by siRNA, Lin28-induced neurite
      underdevelopment was rescued with reduction of Lin28-downstream molecules, high
      mobility group AT-Hook 2, and insulin-like growth factor 1 receptor. Finally,
      Lin28-electroporated mice showed significant memory deficits as assessed by the
      Morris water maze test. Taken together, these findings demonstrate a new role and
      the essential requirement of Lin28 in developmental control of neurite outgrowth,
      which has an impact on synaptic plasticity and spatial memory. These findings
      suggest that targeting Lin28 may attenuate intellectual disabilities by
      correction of impaired dendritic complexity, providing a novel therapeutic
      candidate for treating neurodevelopmental disorders.

PMID- 30203264
TI  - Hypophosphatasia: From Diagnosis to Treatment.
AB  - PURPOSE OF REVIEW: Hypophosphatasia (HPP) is a rare genetic disorder caused by
      mutations of the ALPL gene. ALPL encodes the tissue-non-specific isoenzyme of
      alkaline phosphatase (TNSALP). Consequently, bone mineralization is decreased
      leading to fractures, arthralgia, and extra-skeletal manifestations including
      tissue calcification, respiratory failure, and neurological complications. This
      review summarizes the most important clinical findings, diagnosis, and treatment
      options for HPP. RECENT FINDINGS: Asfotase alfa is a recombinant human alkaline
      phosphatase, used as treatment for the underlying cause of HPP. Asfotase alfa
      enhances the survival in life-threatening HPP and improves bone mineralization,
      muscle strength, and pulmonary function. However, discontinuation of asfotase
      alfa leads to reappearance of bone hypomineralization. Due to its varied
      manifestations, HPP often mimics rheumatological and other bone diseases, thereby
      delaying its diagnosis. Asfotase alfa, a recombinant alkaline phosphatase, is
      available for the long-term enzyme replacement therapy in patients with pediatric
      onset HPP to treat the bone manifestations of the disease.

PMID- 30203266
TI  - Preventive factors related to brucellosis among rural population using the
      PRECEDE model: an application of path analysis.
AB  - The purpose of this model-based study was to identify behavioral and
      environmental prevention factors for brucellosis and to determine the causal
      linkage among these factors in a rural area with high prevalence of the disease.
      A multi-stage random sampling method was used to select villages in Ahar County,
      located in East Azerbaijan Province, Iran. Participants (n = 400) were recruited
      from these villages. Data was collected in accordance with the PRECEDE model
      established in March 2016. This model consists of four phases intended to assess
      each participant's health and quality of life. Standardized, structured
      questionnaires exploring different aspects of brucellosis prevention
      (predisposing, reinforcing, enabling, environmental, and behavioral factors) were
      used. Path analysis was applied to assess the pathway structure of the PRECEDE
      model. Overall, the model fitted the data well (chi2/df = 1.10; RMSEA = .016 (CI
      95%: 0.00-0.07), SRMR = .02, CFI = .99). Significant positive associations were
      found among predisposing, reinforcing, and enabling factors on the one hand, and
      behavior, on the other hand. The predisposing factors showed significant positive
      associations with general health, and the reinforcing factors and general health
      showed significant positive associations with health-related quality of life
      (HRQOL). The results of this study support the use of the PRECEDE model for
      brucellosis prevention, and suggest that a high level of general health, in
      combination with reinforcing factors can increase HRQOL in an area with a high
      prevalence of brucellosis.

PMID- 30203265
TI  - Sulfuric Acid Assisted Preparation of Red-Emitting Carbonized Polymer Dots and
      the Application of Bio-Imaging.
AB  - Red-emitting carbonized polymer dots (CPDs) was prepared from p-phenylenediamine
      (p-PD) aqueous solution with the assistance of sulfuric acid (H2SO4), and the
      optical properties and bio-imaging application were studied in this paper.
      Compared with other strong acids-assisted systems, SA-CPDs (prepared from H2SO4
      assisted system, average diameter is ~ 5 nm) is the brightest. The
      photoluminescence Quantum Yields (QYs) is 21.4% (in water), and the product yield
      is 16.5%. SA-CPDs aqueous solution emits at 600 nm when excited by the light from
      300 to 580 nm. The emission wavelength is independent on the excitation
      wavelength. Formation energies of CPDs in two ways were calculated to show that
      longitudinal growth (forming polymers) is difficult, and the transverse growth
      (forming CPDs) is easy. In addition, the two-photon photoluminescence properties
      (emitting at 602 nm when excited by 850 nm femtosecond pulse laser) of SA-CPDs
      were also utilized in the experiments for HeLa cells staining and shown to have
      potential applications in bio-imaging.

PMID- 30203267
TI  - Proof of concept and improvement of a triple chamber biosystem coupling anaerobic
      digestion, nitrification and mixotrophic endogenous denitrification for organic
      matter, nitrogen and sulfide removal from domestic sewage.
AB  - In this study, two versions of a triple chamber biosystem, coupling anaerobic
      digestion, nitrification and mixotrophic endogenous denitrification (ADNMED),
      were evaluated and compared. They were designed to maximize the use of endogenous
      electron donors produced by anaerobic digestion (residual organic matter and
      sulfide) to abate a portion of the influent nitrogen contained in domestic sewage
      while removing the inconvenience of effluent sulfide. The first version was able
      to abate 40% of the influent nitrogen but presented operational and hydrodynamic
      problems, which resulted in sulfide emissions. A modified second version was
      proposed, improving the first approach and achieving a nitrogen abatement of more
      than 60% and a sulfide-free effluent, complying with local emission standards.
      The results demonstrated that endogenous electron donors produced by anaerobic
      digestion should not be neglected, and a significant cost reduction in nitrogen
      removal from domestic sewage could be achieved by exploiting their potential with
      novel reactor configurations.

PMID- 30203268
TI  - Microvascular Density and Circulating Endothelial Progenitor Cells Before and
      After Treatment with Incretin Mimetics in Diabetic Patients.
AB  - INTRODUCTION: Glucagon-like peptide 1-receptor agonists (incretin mimetics) and
      dipeptidyl peptidase-4 inhibitors (incretin enhancers) have been recently
      introduced in the treatment of diabetes mellitus. In particular, incretin
      mimetics seems to have ancillary antioxidant/antinflammatory properties that
      might be involved in endothelial protection. AIM: To investigate the effect of
      incretin mimetic therapy (liraglutide, exenatide) given to 11 patients with type
      2 diabetes mellitus, on circulating endothelial progenitor cells (EPCs) (bone
      marrow-derived cells possibly participating in neovascularization and endothelial
      protection and repair) and capillary density. METHODS: Four diabetic patients
      were treated with exenatide (5 MUg twice daily for 4 weeks and then 10 MUg twice
      daily for 3 weeks) and 7 with liraglutide (0.6 mg per day for 1 week and then 1.2
      mg per day for 3 weeks). Peripheral venous blood samples were obtained before
      treatment (basal) and after 4 week in patients treated with liraglutide, and
      after 4 and 7 weeks in patients treated with exenatide, since drug titration is
      usually longer. EPCs were evaluated by flow cytometry as CD34+/KDR+ cells.
      Capillary density was evaluated by videomicroscopy, before and after venous
      congestion, in the dorsum of the 4th finger. RESULTS: Patients treated with
      liraglutide (6 males 1 female, age 54 +/- 12 years) showed a decrease in body
      mass index and blood pressure during treatment, while patients treated with
      exenatide (3 males 1 female, age 57 +/- 6 years) did not show any relevant
      change. EPCs were significantly increased after treatment with exenatide, but not
      after treatment with liraglutide. Capillary density was slightly increased only
      after 4 weeks of treatment with exenatide, however the increase was no longer
      present at the final evaluation. CONCLUSIONS: Treatment with exenatide, but not
      with liraglutide, was able to increase the number of circulating EPCs, possibly
      through an antioxidative/antiinflammatory effect.

PMID- 30203270
TI  - Impacts of the Dependent Care Expansion on the Allocation of Mental Health Care.
AB  - We examine the impact of insurance expansion under the Affordable Care Act's
      Dependent Care Expansion (DCE) on allocation of mental health care across illness
      severity, types of care and racial/ethnic groups. Evidence suggests that the
      increase in mental health care utilization resulting from the DCE was restricted
      to individuals with clinically significant mental health conditions. There is no
      evidence suggesting that the increase occurred disproportionately in medication
      only treatment or that it increased racial/ethnic disparities. The DCE appears to
      have been successful in increasing utilization of mental health care among a high
      need group without lowering quality or increasing disparities.

PMID- 30203271
TI  - DT-Diaphorase Prevents Aminochrome-Induced Lysosome Dysfunction in SH-SY5Y Cells.
AB  - Aminochrome has been reported to induce lysosomal dysfunction by inhibiting the
      vacuolar H-type ATPase localized in lysosome membrane. DT-diaphorase has been
      proposed to prevent aminochrome neurotoxicity but it is unknown whether this
      enzyme prevents aminochrome-induced lysosomal dysfunction. In the present study,
      we tested the protective role of DT-diaphorase in lysosomal dysfunction by
      generating a cell line (SH-SY5YsiNQ7) with a stable expression of a siRNA against
      DT-diaphorase with only 10% expression of mRNA enzyme. The cells differentiated
      with retinoic acid and 12-o-tetradecanoylphorbol-13-acetate show a significant
      increase in the expression of tyrosine hydroxylase, vesicular monoamine
      transporter-2, and dopamine transporter. The incubation of SH-SY5YsiNQ7 cells
      with 10 MUM aminochrome resulted in a significant decrease of lysosome pH
      determined by using acridine orange, while aminochrome has no effect on SH-SY5Y
      cells. These results support the proposed protective role of DT-diaphorase
      against aminochrome-induced lysosomal dysfunction.

PMID- 30203269
TI  - Microlaryngoscopic surgery for pyriform sinus fistulas in children: a report of
      two cases.
AB  - BACKGROUND: A pyriform sinus fistula (PSF) is a rare branchial anomaly that
      causes recurrent cervical infections. Open neck surgery has widely been accepted
      as a definitive treatment for PSFs, and endoscopic surgery has been reported in
      recent years. However, both approaches are not satisfactory because of high
      recurrence rates and postoperative complications. Microlaryngoscopic surgery
      (MLS) is a transoral surgical technique involving the use of an operating
      microscope. In this report, we present a new procedure involving MLS for
      resection and closure of a PSF without a skin incision. CASE PRESENTATION:
      Technique: MLS was performed under general anesthesia with endotracheal
      intubation. The patient was placed in the supine position, and a direct
      laryngoscope was inserted to expose the pyriform sinus, which was then magnified
      using an operating microscope. The mucosal layer was carefully resected using
      scissors and cupped forceps with sharp edges. The fistula was securely sutured
      using absorbable suture material. Case 1: A 9-year-old boy with recurrent neck
      abscesses since 8 years of age presented to our hospital after receiving
      antibiotics and undergoing drainage in other hospitals. After admission to our
      hospital, barium esophagography and oral contrast coronal computed tomography
      showed a PSF on the left side, and open neck surgery was performed to resect the
      fistula. He was eventually discharged from the hospital without any problem.
      However, a PSF recurred 2 weeks later. As reoperation with the cervical approach
      was considered difficult owing to severe adhesions, we adopted MLS as a
      definitive operation. The postoperative course was uneventful. No recurrence was
      observed during an 18-month follow-up. Case 2: A 10-year-old girl presented to
      our hospital with recurrent left-sided neck swelling since 6 years of age. After
      inflammation control, a PSF was identified on the left side on barium
      esophagography and computed tomography. MLS was performed safely, and the
      postoperative course was uneventful. No recurrence was observed during a 10-month
      follow-up. CONCLUSIONS: MLS allows excellent visualization and effective closure
      for PSFs, and this approach is suitable for recurrence after open neck surgery.
      Therefore, MLS might become a first-line treatment for PSFs in children.

PMID- 30203273
TI  - Patch-Clamp Recording of the CRAC Channel Current in STIM-Orai Overexpressing
      Cells.
AB  - Induced by the depletion of ER calcium store, the calcium influx through calcium
      release-activated calcium (CRAC) channels is an ubiquitous way of Ca2+ influx for
      most cell types. This process is mediated by STIM protein, ER calcium sensor, and
      PM localized Orai calcium channels. Biophysical characterization of this STIM
      Orai-mediated current, or ICRAC, with whole-cell patch-clamp technique is
      essential for revealing the molecular mechanisms underlying the process of STIM
      Orai activation or modulation. Here we describe one commonly used procedure of
      monitoring CRAC activity with whole-cell patch-clamp technique.

PMID- 30203272
TI  - Primary Thrombosis Prophylaxis in Persistently Antiphospholipid Antibody-Positive
      Individuals: Where Do We Stand in 2018?
AB  - PURPOSE OF REVIEW: To update our previous literature review and management
      recommendations on risk stratification and primary thrombosis prophylaxis in
      persistently antiphospholipid antibody (aPL)-positive individuals. RECENT
      FINDINGS: The estimated annual thrombosis incident rate (ATIR) among aPL-positive
      individuals with or without systemic autoimmune disease (SAIDx) is 0 to 5.3%,
      probably very low (< 1%/year) in those with no other SAIDx and thrombosis risk
      factors. Risk stratification based on aPL profile, age, additional SAIDx, and
      traditional cardiovascular disease (CVD) or venous thrombosis risk factors is
      crucial to determine the risk of first thrombosis in aPL-positive patients. The
      protective effect of low-dose aspirin for primary thrombosis prophylaxis
      prevention is not supported by randomized controlled data. Hydroxychloroquine is
      protective against thrombosis in aPL-positive SLE patients; however, its role in
      aPL-positive individuals with other SAIDx remains uncertain. Statins downregulate
      proinflammatory and prothrombotic biomarkers among antiphospholipid syndrome
      (APS) patients and may have a role in aPL-positive individuals with high CVD
      risk. The optimal primary thrombosis prevention strategy in patients with
      clinically significant aPL profiles should include (a) regular screening and
      elimination of non-aPL thrombosis risk factors, (b) optimal management of
      concomitant SAIDx,

PMID- 30203275
TI  - Recording SOCE Activity in Neurons by Patch-Clamp Electrophysiology and
      Microfluorometric Calcium Imaging.
AB  - Store-operated Ca2+ entry (SOCE) is a Ca2+ influx pathway at the plasma membrane
      that replenishes intracellular Ca2+ stores in response to depletion of Ca2+
      stores. The SOC current, also known as the Ca2+ release-activated Ca2+ current
      (ICRAC), has a small conductance, which makes selective recording difficult. This
      challenge may be addressed using techniques based on identification of Ca2+
      influx patch-clamp electrophysiological recording and measurement of cytoplasmic
      Ca2+ accumulation with Ca2+-sensitive fluorophores. Here, we describe specific
      methods for studying SOCE using these approaches in rat dorsal root ganglion
      neurons.

PMID- 30203274
TI  - Fluorescence-Based Ratiometric Measurement of CRAC Channel Activity in STIM-Orai
      Overexpressing HEK-293 Cells.
AB  - Calcium influx through store-operated Ca2+ entry (SOCE), mediated by STIM
      operated Orai channels, is crucial for many cellular functions. To dissect the
      molecular mechanisms underlying the process of STIM-Orai activation and identify
      regulators that modify this process, ratiometric imaging of SOCE responses in HEK
      cells overexpressing STIM and Orai is a routinely used method. Here we describe
      one commonly used procedure of monitoring SOCE activity with a ratiometric
      membrane-permeable dye fura-2-AM. Other ratiometric indicators suitable for SOCE
      measurements are also discussed.

PMID- 30203276
TI  - Mn2+ Quenching Assay for Store-Operated Calcium Entry.
AB  - Store-operated Ca2+ entry (SOCE) pathway plays important roles in many cellular
      processes, which is largely studied by using fluorescent Ca2+ indicator, Fura-2.
      Extracellular Mn2+ is able to cross the plasma membrane through SOCE and quenches
      the fluorescence signals from Fura-2. Thus, the fluorescence quenching rate by
      Mn2+ composes a convenient assay to monitor the extent of SOCE. This chapter
      describes an experimental method of Mn2+ quenching assay for both cultured
      esophageal epithelial and skeletal muscle cells. It also explains how to perform
      a quantitative analysis of graded SOCE.

PMID- 30203277
TI  - Fluorescence-Based Measurements of Store-Operated Ca2+ Entry in Cancer Cells
      Using Fluo-4 and Confocal Live-Cell Imaging.
AB  - The store-operated calcium entry (SOCE) is the predominant calcium entry
      mechanism in cancer cell and other non-exciting cells. In the last few years,
      there is rapidly accumulating evidence supporting that SOCE is dysregulated in
      many types of cancer. The hyperactive SOCE in tumor cells is spatially and
      temporally coded to promote cell proliferation, migration, and invasion. In this
      chapter, we describe two protocols to measure SOCE in tumor cells. The first
      protocol employs fluorescent microplate readers and could be adapted for high
      throughput screening. The second protocol takes advantage of laser scanning
      confocal microscopy and can be used to resolve the high-resolution spatial and
      temporal coding of SOCE signals in single cells. These protocols are useful tools
      to uncover the dysregulation of SOCE signaling in tumor malignancy.

PMID- 30203278
TI  - Fluorescence-Based Measurements of the CRAC Channel Activity in Cell Populations.
AB  - Cytosolic Ca2+ plays an important role in cellular biology, and since its
      identification as a second messenger, a number of techniques and methods to
      analyze the changes in cytosolic Ca2+ concentration ([Ca2+]c) induced by
      physiological agonists have been developed. Changes in [Ca2+]c might be
      determined in single cells or in cell populations. Measurement in single cells
      allows to determine changes in [Ca2+]c at a subcellular level but often results
      in heterogeneous responses among cells. Determination of intracellular Ca2+
      mobilization at the cell population level reduces this heterogeneity and allows
      [Ca2+]c measurements in small cells that load little amounts of indicator. Here,
      we describe the measurement of agonist-evoked changes in [Ca2+]c associated with
      Ca2+ influx in cell populations.

PMID- 30203279
TI  - Indirect Measurement of CRAC Channel Activity Using NFAT Nuclear Translocation by
      Flow Cytometry in Jurkat Cells.
AB  - Flow cytometry is a powerful technology to assess the presence of NFAT in the
      nuclei after CRAC channel activation. Here we described a simplified procedure
      for the analysis of CRAC channel activity using NFAT nuclear translocation by
      flow cytometry, based on the isolation of Jurkat E6-1 cell nuclei.

PMID- 30203280
TI  - CRAC Channel Components Quantitative Expression (In Tissues and Cell Lines) Using
      qPCR.
AB  - Since last decade real-time qPCR has become a routine and robust approach for
      measuring the expression of genes of interest. Indeed, using qPCR, expression
      profile analyses are now possible and participate to the understanding of
      physiological or pathological role of channels such as calcium release-activated
      channels (CRAC). Initially discovered in lymphocyte T and immunity perturbations,
      recent studies have highlighted the role of CRAC channels in other pathologies
      such as cancer. Here we describe a protocol to quantify CRAC components
      expression, in tissue sample and cell lines, to validate knockdown strategies or
      identify their roles in physiological and pathological conditions (Hoth and
      Penner, J Physiol 465:359-386, 1993; Hoth and Penner, Nature 355:353-356, 1992;
      and Zweifach and Lewis, Proc Natl Acad Sci U S A 90:6295-6299, 1993).

PMID- 30203281
TI  - Western Blotting and Co-immunoprecipitation of Endogenous STIM/ORAI and Protein
      Partners.
AB  - The characterization of protein-protein interactions through methods such as co
      immunoprecipitation, followed by Western blot analysis, is a crucial step in the
      understanding of protein functions and the biology of the cell. Since the
      discovery of ORAI and STIM proteins as component of store-operated channel (SOC),
      overexpressing systems have been used to demonstrate how ORAI and STIM can
      associate with physiological and pathological conditions. Here we describe a
      protocol allowing endogenous studies.

PMID- 30203282
TI  - Study of Endogenous CRAC Channels in Human Mast Cells Using an Adenoviral
      Delivery System to Transduce Cells with Orai-Targeting shRNAs or with cDNAs
      Expressing Dominant-Negative Orai Channel Mutations.
AB  - We describe two methods to study CRAC channel function in human lung mast cells.
      Both methods involve suppression of endogenous channel function. In the first we
      use Orai-targeting shRNAs to knock down Orai channel mRNA transcripts. In the
      second we overexpress dominant-negative mutants of the three members of the Orai
      channel family. To overcome the poor transfection efficiency of mast cells, we
      employ an adenoviral delivery system for cell transduction. Knockdown of CRAC
      channel transcripts is assessed initially using quantitative RT-PCR. We describe
      an assay for beta-hexosaminidase release as a measure of mast cell degranulation
      to assess the effect of overexpression of dominant-negative mutants.

PMID- 30203283
TI  - Store-Operated Ca2+ Entry in Drosophila Primary Neuronal Cultures.
AB  - Intracellular calcium signals in neurons frequently derive from the stimulation
      of G protein-coupled receptors (GPCR) by neurotransmitters, neuropeptides, and
      neurohormones. GPCR stimulation in neurons leads to generation of inositol 1,4,5
      trisphosphate (IP3), which in turn activates endoplasmic reticulum (ER)-localized
      IP3 receptors. The IP3 receptor (IP3R) is a ligand-gated Ca2+ channel, which
      releases Ca2+ from ER stores. In Drosophila neurons it has been shown that
      depletion of ER Ca2+ store is followed by store-operated Ca2+ entry (SOCE)
      through STIM and Orai, the ER Ca2+ sensor and the plasma membrane Ca2+ channel
      respectively. The elucidation of this Ca2+ signaling pathway in neurons has in
      part been possible due to the ease of genetic manipulation in Drosophila, which
      has allowed neuron-specific knockdown of various proteins of interest. This has
      been followed by standardization of conditions for culturing neurons from
      dissected brains of the relevant genotypes, such that they could be used for
      robust Ca2+ measurements by imaging with standard Ca2+ indicator dyes. Protocols
      for measurement of IP3-mediated Ca2+ release, passive depletion of ER Ca2+ store,
      and SOCE in primary cultures of Drosophila neurons are described here.

PMID- 30203284
TI  - Study of the Endogenous CRAC Channel Using shRNA-Mediated Gene Silencing.
AB  - The Ca2+ release-activated Ca2+ (CRAC) current is a major signaling event in non
      excitable cells whereby Ca2+ store depletion activates Ca2+ entry across the
      plasma membrane from the extracellular space. Stromal interaction molecule 1
      (STIM1) and Orai1 proteins are the key molecular players of the CRAC channel.
      Previous studies have linked activity of this channel to many physiological
      functions, and dysregulation of the CRAC channel has been associated with various
      diseases. In the absence of inducible tissue-specific knockout mice, in vivo
      knockdown studies examining the endogenous function of CRAC channel proteins,
      STIM1 and Orai1, are a challenge. In this chapter, we describe a lentiviral
      delivery system of shRNA-mediated gene silencing that has proven successful in
      studying the endogenous CRAC channel in vivo.

PMID- 30203285
TI  - Engineered Cross-Linking to Study the Pore Architecture of the CRAC Channel.
AB  - ORAI1 constitutes the pore-forming subunit of the calcium release-activated
      calcium (CRAC) channel, a prototypical store-operated channel that is essential
      for the activation of cells of the immune system. Here we describe a convenient
      yet powerful cross-linking approach to examine the pore architecture of CRAC
      channels using ORAI1 proteins engineered to contain one or two cysteine residues.
      The generalizable cross-linking in situ approach can also be readily extended to
      study other integral membrane proteins expressed in various types of cells.

PMID- 30203286
TI  - Measurement of the CRAC Channel Fast Ca2+-Dependent Inactivation (FCDI).
AB  - Fast Ca2+-dependent inactivation (FCDI) is a safety mechanism limiting Ca2+ entry
      through some types of Ca2+ channels, including Ca2+ release-activated Ca2+ (CRAC)
      channels. This type of inactivation is caused by Ca2+, which passes through Ca2+
      channel and binds to a specific site within a short distance from the inner mouth
      of the pore, causing channel to shut.The main technique that is used to
      investigate FCDI is whole-cell patch clamping. Since the cloning of the molecular
      components of the CRAC channel, STIM1 and Orai1, FCDI of CRAC channel has been
      studied using HEK293T heterologous expression system. In this paper we describe a
      method of quantifying CRAC channel FCDI by using instantaneous tail currents.

PMID- 30203287
TI  - High-Resolution Imaging of STIM/Orai Subcellular Localization Using Array
      Confocal Laser Scanning Microscopy.
AB  - The expression of chimeras that consist of a fluorescent protein (FP) conjugated
      with a protein of interest provides the ability to visualize, track, and quantify
      the subcellular localization and dynamics of specific proteins in biological
      samples. Array confocal laser scanning microscopy is an eminently suitable
      technique for live-cell imaging of FP-tagged fusion proteins. Here, we describe
      real-time monitoring of the subcellular dynamics of the stromal-interacting
      molecule 1 (STIM1) and Orai1, the key protagonists of store-operated Ca2+ entry
      (SOCE) under resting conditions, and upon Ca2+ mobilization from the endoplasmic
      reticulum (ER).

PMID- 30203288
TI  - Single-Channel Single-Molecule Detection (SC-SMD) System.
AB  - The combination of single-molecule fluorescence imaging and electrophysiology
      provides a powerful tool to explore the stoichiometry and functional properties
      of ionic channels, simultaneously. Here, we describe a typical SC-SMD experiment
      from the preparation of plasmids containing the genes encoding for the channels
      of interest fused to fluorescent proteins to the use of the SC-SMD system for
      simultaneous patch clamping and single-molecule determinations.

PMID- 30203289
TI  - Loss of odor-induced c-Fos expression of juxtaglomerular activity following
      maintenance of mice on fatty diets.
AB  - Diet-induced obesity (DIO) decreases the number of OMP+ olfactory sensory neurons
      (OSN) in the olfactory epithelium by 25% and reduces correlate axonal projections
      to the olfactory bulb (OB). Whether surviving OSNs have equivalent odor
      responsivity is largely unknown. Herein, we utilized c-fos immediate-early gene
      expression to map neuronal activity and determine whether mice weaned to control
      (CF), moderately-high fat (MHF), or high-fat (HF) diet for a period of 6 months
      had changes in odor activation. Diet-challenged M72-IRES-tau-GFP mice were
      exposed to either a preferred M72 (Olfr160) ligand, isopropyl tiglate, or clean
      air in a custom-made Bell-jar infusion chamber using an alternating odor exposure
      pattern generated by a picosprizerTM. Mice maintained on fatty diets weighed
      significantly more and cleared glucose less efficiently as determined by an
      intraperitoneal glucose tolerance test (IPGTT). The number of juxtaglomerular
      cells (JGs) decreased following maintenance of the mice on the MHF diet for cells
      surrounding the medial but not lateral M72 glomerulus within a 4 cell-column
      distance. The percentage of c-fos + JGs surrounding the lateral M72 glomerulus
      decreased in fat-challenged mice whereas those surrounding the medial glomerulus
      were not affected by diet. Altogether, these results show an asymmetry in the
      responsiveness of the 'mirror image' glomerular map for the M72 receptor that
      shows greater sensitivity of the lateral vs. medial glomerulus upon exposure to
      fatty diet.

PMID- 30203290
TI  - Correction to: Blalock-Taussig Shunt Size: Should it be Based on Body Weight or
      Target Branch Pulmonary Artery Size?
AB  - The original version of the article unfortunately contained an alignment error in
      Table 1. The correct version of Table 1 is given below.

PMID- 30203291
TI  - Cost Savings Analysis of Early Extubation Following Congenital Heart Surgery.
AB  - The clinical benefit of early extubation following congenital heart surgery has
      been demonstrated; however, its effect on resource utilization has not been
      rigorously evaluated. We sought to determine the cost savings of implementing an
      early extubation pathway for children undergoing surgery for congenital heart
      disease. We performed a cost savings analysis after implementation of an early
      extubation strategy among children undergoing congenital heart surgery at British
      Columbia Children's Hospital (BCCH) over a 2.5-year period. All patients
      undergoing one of the eight Society of Thoracic Surgeons (STS) benchmark
      operations, ASD repair, or bidirectional cavopulmonary anastomosis were included
      in the analysis (n = 370). We compared our data to aggregate STS multi
      institutional data from a contemporary cohort. We estimated daily costs for ICU
      care, ward care, medications, imaging, additional procedures, and allied health
      care using an administrative database. Direct costs, indirect costs, and cost
      savings were estimated. Simulation methods, Monte Carlo, and bootstrapping were
      used to calculate the 95% credible intervals for all estimates. The mean cost
      savings per procedure was $12,976 and the total estimated cost savings over the
      study period at BCCH was $4.8 million with direct costs accounting for 91% of
      cost savings. Sensitivity analysis demonstrated a mean cost savings range of
      $11,934-$14,059 per procedure. Early extubation is associated with substantial
      cost savings due to reduced hospital resource utilization. Implementation of an
      early extubation strategy following congenital heart surgery may contribute to
      improved resource utilization.

PMID- 30203292
TI  - Evaluation of Left Ventricular Function Long Term After Arterial Switch Operation
      for Transposition of the Great Arteries.
AB  - Long-term after arterial switch operation for transposition of the great
      arteries, abnormal coronary anatomy and altered loading conditions could
      compromise ventricular function. The current study investigates whether left
      ventricular function, measured with echocardiographic bi-plane ejection fraction
      and deformation imaging, in patients long term after arterial switch operation
      for transposition of the great arteries differs from healthy peers. A cross
      sectional cohort study of patients at least 12 years after arterial switch
      operation was analyzed with bi-plane Simpson's left ventricular ejection fraction
      (LVEF) and deformation (speckle tracking) echocardiography. 81 patients, median
      age 20.6 (interquartile range 13.5-28.4) years, were included. LVEF was normal on
      average at 55.5 +/- 6.1%. Global longitudinal strain (GLS) was lower in patients
      compared to healthy peers throughout all age groups and on pooled average (- 15.4
      +/- 1.1% vs. - 23.2 +/- 0.9%). Although LVEF is normal on average in patients
      after arterial switch operation for transposition of the great arteries, GLS is
      impaired compared to healthy peers. The reduced GLS could indicate sub-clinical
      myocardial dysfunction.

PMID- 30203293
TI  - Drug-Induced Loss of Preexcitation in Pediatric Patients with WPW Pattern During
      Electrophysiologic Study.
AB  - Ablation of accessory pathways (AP) is one of the most often performed procedures
      in pediatric electrophysiology. In pediatric patients these procedures are mostly
      performed in anaesthesia or sedation. In some of these patients who are referred
      for electrophysiologic (EP) study, we could observe disappearance of the
      preexcitation, i.e. antegrade conduction of an AP during introduction of
      sedation. As a suppression of AP conduction capacities has been reported as
      negative side effect of propofol and other anaesthetics, the aim of this study
      was to evaluate risk factors for drug-induced suppression of AP conduction
      properties. Consecutive, pediatric patients with Wolff-Parkinson-White (WPW)
      pattern referred for EP study in the period of 2016-2017 were reviewed in
      retrospect. Patients with complex congenital heart disease were excluded. An
      entire chart review including ECG, bicycle stress testing, and periprocedural
      data was performed. In 4 of 37 patients included into the study, loss of
      preexcitation could be observed during sedation. Data analysis showed weaker
      conduction capacities of the AP as a risk factor (p = 0.009). Interestingly,
      absolute (p = 0.11) or adjusted to body weight (p = 0.92) drug doses were not a
      relevant risk factor. Patients with WPW and weaker conduction capacities of the
      AP, as implied by an early disappearance of preexcitation during exercise stress
      testing, seem to be more prone to drug-induced suppression of an AP.

PMID- 30203294
TI  - Comparative RNA-Seq analysis on the regulation of cucumber sex differentiation
      under different ratios of blue and red light.
AB  - Cucumber (Cucumis sativus L.) is a typical monoecism vegetable with individual
      male and female flowers, which has been used as a plant model for sex
      determination. It is well known that light is one of the most important
      environmental stimuli, which control the timing of the transition from vegetative
      growth to reproductive development. However, whether light controls sex
      determination remains elusive. To unravel this problem, we performed high
      throughput RNA-Seq analyses, which compared the transcriptomes of shoot apices
      between R2B1(Red light:Blue light = 2:1)-treated and R4B1(Red light:Blue light =
      4:1)-treated cucumber seedlings. Results showed that the higher proportion of
      blue light in the R2B1 treatment significantly induced the formation of female
      flowers and accelerated female flowering time in this whole study. The genes
      related to flowering time, such as flowering locus T (FT) and SUPPRESSOR OF
      OVEREXPRESSION OF CO1 (SOC1), were up-regulated after R2B1 treatment.
      Furthermore, the transcriptome analysis showed that up-regulation and down
      regulation of specific DEGs (the differentially expressed genes) were primarily
      the result of plant hormone signal transduction after treatments. The specific
      DEGs related with auxin formed the highest percentage of DEGs in the plant
      hormone signal transduction. In addition, the expression levels of transcription
      factors also changed after R2B1 treatment. Thus, sex differentiation affected by
      light quality might be induced by plant hormone signal transduction and
      transcription factors. These results provide a theoretical basis for further
      investigation of the regulatory mechanism of female flower formation under
      different light qualities in cucumber seedlings.

PMID- 30203295
TI  - Effects of eccentric training with different training frequencies on blood
      circulation, collagen fiber orientation, and mechanical properties of human
      Achilles tendons in vivo.
AB  - PURPOSE: The purpose of the present study was to compare the effects of eccentric
      training with different training frequencies on the blood circulation, collagen
      orientation, and mechanical properties of the human Achilles tendon in vivo.
      METHODS: Ten healthy males completed 12 weeks of a unilateral eccentric training
      program {(15 repetitions with knee straight and 15 repetitions with knee slightly
      bent) * 6 sets in a single session} for the plantar flexor muscles. They
      performed training three times per week on one side (3TW) and six times per week
      on the other side (6TW). Before and after training, changes in blood volume,
      coefficient of variation (CV) of echogenicity (reflects collagen fiber
      orientation), and stiffness of the Achilles tendon were compared by two-way
      analysis of variance. RESULTS: The tendon blood volume tended to increase after
      3TW and 6TW (p = 0.064). Tendon stiffness did not change after 3TW and 6TW,
      whereas the elongation of tendon structures at three force levels (50, 100, and
      150 N) significantly decreased with 3TW, but not 6TW. The CV of echogenicity
      significantly decreased after 3TW and 6TW. However, no significant differences
      were observed in the relative changes in these measured variables between 3TW and
      6TW. CONCLUSION: The present results demonstrated an increase in blood volume,
      the alignment of collagen fibers, and unchanged stiffness of the Achilles tendon
      after 12 weeks of eccentric training. Furthermore, the training frequency did not
      influence these training-induced changes in the tendon properties.

PMID- 30203296
TI  - The effect of hot and cold drinks on thermoregulation, perception, and
      performance: the role of the gut in thermoreception.
AB  - PURPOSE: Hot compared to cold drinks alter sweating responses during very low
      intensity exercise in temperate conditions. The thermoregulatory, perceptual, and
      performance effects of hot compared to cold drinks in hot, dry conditions during
      high-intensity exercise have not been examined. METHOD: Ten participants [mean +/
      SD characteristics age 25 +/- 5 years, height 1.81 +/- 0.07 m, body mass 73.5 +/
      10.6 kg, maximal power output (PMax) 350 +/- 41 W] completed two conditions,
      where they drank four boluses (ingested at - 9, 15, 30, and 45 min, respectively)
      of 3.2 mL kg- 1 (~ 960 mL total) of either a COLD (5.3  degrees C) or a HOT drink
      (49.0  degrees C), which were contrasted to a no-drink CONTROL. They cycled for
      60-min [55% PMax in hot (34.4  degrees C) dry (34% RH)] ambient conditions
      followed by a test to exhaustion (TTE; 80% PMax). The thermoregulatory,
      performance, and perceptual implications of drink temperature were measured.
      RESULTS: TTE was worse in the CONTROL (170 +/- 132 s) than the COLD drink (371 +/
      272 s; p = 0.021) and HOT drink conditions (367 +/- 301 s; p = 0.038) which were
      not different (p = 0.965). Sweat responses [i.e., reflex changes in mean skin
      temperature (Tmsk) and galvanic skin conductance] indicated transient reductions
      in sweating response after COLD drink ingestion. The COLD drink improved thermal
      comfort beyond the transient changes in sweating. CONCLUSION: Only COLD drink
      ingestion changed thermoregulation, but improved perceptual response.
      Accordingly, we conclude a role for gut thermoreception in thermal perception
      during exercise in hot, dry conditions.

PMID- 30203297
TI  - Clinical features and outcome of patients with acute respiratory failure
      revealing anti-synthetase or anti-MDA-5 dermato-pulmonary syndrome: a French
      multicenter retrospective study.
AB  - BACKGROUND: Anti-synthetase (AS) and dermato-pulmonary associated with anti-MDA-5
      antibodies (aMDA-5) syndromes are near one of the other autoimmune inflammatory
      myopathies potentially responsible for severe acute interstitial lung disease. We
      undertook a 13-year retrospective multicenter study in 35 French ICUs in order to
      describe the clinical presentation and the outcome of patients admitted to the
      ICU for acute respiratory failure (ARF) revealing AS or aMDA-5 syndromes.
      RESULTS: From 2005 to 2017, 47 patients (23 males; median age 60 [1st-3rd
      quartiles 52-69] years, no comorbidity 85%) were admitted to the ICU for ARF
      revealing AS (n = 28, 60%) or aMDA-5 (n = 19, 40%) syndromes. Muscular, articular
      and cutaneous manifestations occurred in 11 patients (23%), 14 (30%) and 20 (43%)
      patients, respectively. Seventeen of them (36%) had no extra-pulmonary
      manifestations. C-reactive protein was increased (139 [40-208] mg/L), whereas
      procalcitonine was not (0.30 [0.12-0.56] ng/mL). Proportion of patients with
      creatine kinase >= 2N was 20% (n = 9/47). Forty-two patients (89%) had ARDS,
      which was severe in 86%, with a rate of 17% (n = 8/47) of extra-corporeal
      membrane oxygenation requirement. Proportion of patients who received
      corticosteroids, cyclophosphamide, rituximab, intravenous immunoglobulins and
      plasma exchange were 100%, 72%, 15%, 21% and 17%, respectively. ICU and hospital
      mortality rates were 45% (n = 21/47) and 51% (n = 24/47), respectively. Patients
      with aMDA-5 dermato-pulmonary syndrome had a higher hospital mortality than those
      with AS syndrome (n = 16/19, 84% vs. n = 8/28, 29%; p = 0.001). CONCLUSIONS:
      Intensivists should consider inflammatory myopathies as a cause of ARF of unknown
      origin. Extra-pulmonary manifestations are commonly lacking. Mortality is high,
      especially in aMDA-5 dermato-pulmonary syndrome.

PMID- 30203298
TI  - HIF-1alpha/Beclin1-Mediated Autophagy Is Involved in Neuroprotection Induced by
      Hypoxic Preconditioning.
AB  - Hypoxic preconditioning (HPC) exerts a protective effect against hypoxic/ischemic
      brain injury, and one mechanism explaining this effect may involve the
      upregulation of hypoxia-inducible factor-1 (HIF-1). Autophagy, an endogenous
      protective mechanism against hypoxic/ischemic injury, is correlated with the
      activation of the HIF-1alpha/Beclin1 signaling pathway. Based on previous
      studies, we hypothesize that the protective role of HPC may involve autophagy
      occurring via activation of the HIF-1alpha/Beclin1 signaling pathway. To test
      this hypothesis, we evaluated the effects of HPC on oxygen-glucose
      deprivation/reperfusion (OGD/R)-induced apoptosis and autophagy in SH-SY5Y cells.
      HPC significantly attenuated OGD/R-induced apoptosis, and this effect was
      suppressed by the autophagy inhibitor 3-methyladenine and mimicked by the
      autophagy agonist rapamycin. In control SH-SY5Y cells, HPC upregulated the
      expression of HIF-1alpha and downstream molecules such as BNIP3 and Beclin1.
      Additionally, HPC increased the LC3-II/LC3-I ratio and decreased p62 levels. The
      increase in the LC3-II/LC3-I ratio was inhibited by the HIF-1alpha inhibitor YC-1
      or by Beclin1-short hairpin RNA (shRNA). In OGD/R-treated SH-SY5Y cells, HPC also
      upregulated the expression levels of HIF-1alpha, BNIP3, and Beclin1, as well as
      the LC3-II/LC3-I ratio. Furthermore, YC-1 or Beclin1-shRNA attenuated the HPC
      mediated cell viability in OGD/R-treated cells. Taken together, our results
      demonstrate that HPC protects SH-SY5Y cells against OGD/R via HIF-1alpha/Beclin1
      regulated autophagy.

PMID- 30203299
TI  - New approaches to NAD(P)H regeneration in the biosynthesis systems.
AB  - Nicotinamide adenine dinucleotide (NADH) and nicotinamide adenine dinucleotide
      phosphate (NADPH), as two kinds of well-known cofactor, are widely used in the
      most of enzymatic redox reactions, playing an important role in industrial
      catalysis. In general, supply of NAD(P)H is a major challenged factor in redox
      fermentation systems due to its high cost and low stability, which have
      stimulated the development of NADH regeneration systems in recent years. Until
      now, a series of NAD(P)H regeneration systems have been developed. This review
      focuses primarily on new approaches of NAD(P)H cofactor regeneration in the
      biosynthesis systems, such as single cell in vivo NADH regeneration system,
      double cell coupling NADH regeneration system, in vitro enzyme-coupled NADH
      regeneration system, microbial cell surface display NADH regeneration system.
      Finally, the prospect and tendency of NADH regeneration are discussed.

PMID- 30203301
TI  - Association between preoperative anaemia and blood transfusion with long-term
      functional and quality of life outcomes amongst patients undergoing primary total
      knee arthroplasty in Singapore: a single-centre retrospective study.
AB  - PURPOSE: Preoperative anaemia affects up to one-third of patients undergoing
      total knee arthroplasty (TKA) and is associated with increased blood transfusion
      and prolonged hospitalisation. Prior studies have associated preoperative anaemia
      with poorer functional recovery after total hip arthroplasty. However, the
      association between preoperative anaemia and functional outcomes following TKA is
      unknown. We aim to determine whether preoperative anaemia and perioperative blood
      transfusion affect health-related quality of life (HRQoL) and functional outcomes
      following TKA. METHODS: Retrospective analysis of 1994 patients who underwent
      primary unilateral TKA from 2013 to 2014 was performed. Anaemia was defined
      according to the World Health Organisation definition. Baseline and 6-month
      postoperative HRQoL was assessed with the 36-Item Short Form Survey (SF-36),
      while function was assessed with Oxford Knee Score (OKS) and Knee Society
      Function Score (KSFS). Physical function (PF), role physical (RP), bodily pain
      (BP), social function (SF) and role emotional (RE) domains of SF-36, OKS and KSFS
      demonstrated significant change greater than the minimal clinically important
      difference between baseline and 6 months. Analysis of covariance (ANCOVA) was
      performed to identify predictors of 6-month scores. RESULTS: The incidence of
      preoperative anaemia was 22.3%. 4.3% of patients received blood transfusions.
      Preoperative anaemia and perioperative blood transfusion did not significantly
      affect SF-36, KSFS and OKS scores at 6 months postoperatively. Poor baseline SF
      36, KSS and OKS scores and high BMI >= 37.5 kg/m2 are consistently associated
      with lower scores at 6 months. CONCLUSION: Preoperative anaemia and perioperative
      blood transfusion did not significantly affect HRQoL and functional outcomes
      following primary TKA. Poor baseline and obesity were associated with poorer
      outcomes.

PMID- 30203302
TI  - Validation of two PROMIS item banks for measuring social participation in the
      Dutch general population.
AB  - BACKGROUND: The Patient-Reported Outcomes Measurement Information System (PROMIS)
      item banks 'Ability to Participate in Social Roles and Activities' (35 items) and
      'Satisfaction with Social Roles and Activities' (44 items) were developed to
      measure (satisfaction with) participation more efficiently and precisely than
      current instruments, by using Computerized Adaptive Testing (CAT). We validated
      these item banks in a Dutch general population. METHODS: Participants in an
      internet panel completed both item banks. Unidimensionality, local dependence,
      monotonicity, Graded Response Model item fit, Differential Item Functioning (DIF)
      for age, gender, education, region, ethnicity, and language (Dutch compared to US
      Social Supplement), and reliability were assessed. RESULTS: A representative
      Dutch sample of 1002 people participated. We found for the Ability to Participate
      and Satisfaction with Participation item banks, respectively, sufficient
      unidimensionality (CFI: 0.971, 0.960; TLI: 0.970, 0.958; RMSEA: 0.108, 0.108), no
      local dependence, sufficient monotonicity (H: 0.75, 0.73), good item fit (2 out
      of 35 items, 1 out of 44 items with S-X2 p-value < 0.001). No DIF was found. We
      found a reliability of at least 0.90 with simulated CATs in 86% and 94% of the
      participants with on average 4.7 (range 2-12) and 4.3 (range 3-12) items,
      respectively. DISCUSSION: The PROMIS participation item banks showed sufficient
      psychometric properties in a general Dutch population and can be used as CAT.
      PROMIS CATs allow reliable and valid measurement of participation in an efficient
      and user-friendly way with limited administration time.

PMID- 30203300
TI  - The role of childhood trauma and stress reactivity for increased alcohol craving
      after induced psychological trauma: an experimental analogue study.
AB  - BACKGROUND: Traumatic events are associated with alcohol use problems with
      increased alcohol craving as a potential mediator. There is still a lack of
      knowledge regarding the causal nature of this association and its underlying
      mechanisms. This study investigated the effects of acute trauma exposure on
      alcohol craving in healthy individuals considering the role of stress reactivity
      and childhood trauma (CT) using a laboratory randomized controlled design.
      METHODS: Ninety-five healthy participants were randomly exposed to a trauma or a
      neutral film. History of CT, and pre- to post-film changes in craving (craving
      reactivity, CR), anxiety, skin conductance, heart rate, and saliva cortisol
      levels were assessed. Moreover, associations between trauma film exposure and CR,
      the moderating role of CT, and associations between CT, stress reactivity, and
      trauma-induced CR were analyzed. RESULTS: Relative to the neutral film, the
      trauma film elicited an increase in CR in females but not in males. In males but
      not in females, the association between trauma film exposure and CR was moderated
      by CT, with trauma-induced CR increasing with the number of CT. In males, CT was
      related to decreased cortisol reactivity and increased heart rate and skin
      conductance response of which skin conductance was also associated with CR.
      DISCUSSION: These findings provide further evidence for a causal link between
      traumatic experiences and CR. While this association seems to be stronger in
      females, males might still be at risk in case of other vulnerability factors such
      as CT, with altered sympathetic stress reactivity as a potential contributing
      mechanism.

PMID- 30203304
TI  - Striosome-based map of the mouse striatum that is conformable to both cortical
      afferent topography and uneven distributions of dopamine D1 and D2 receptor
      expressing cells.
AB  - The striatum is critically involved in execution of appropriate behaviors, but
      its internal structures remain unmapped due to its unique structural
      organization, leading to ambiguity when interpreting heterogeneous properties of
      striatal neurons that differ by location. We focused on site-specific diversity
      of striosomes/matrix compartmentalization to draw the striatum map. Five types of
      striosomes were discriminated according to diverse immunoreactivities for the u
      opioid receptor, substance P (SP) and enkephalin, and each type occupied a
      particular domain inside the striatum. Furthermore, there was an additional
      domain lacking striosomes. This striosome-free space was located at the
      dorsolateral region and received afferents preferentially from the primary motor
      and sensory cortices, whereas the striosome-rich part received afferents from
      associational/limbic cortices, with topography inside both innervations. The
      proportion of dopamine D1 receptor-expressing, presumptive striatonigral neurons
      was approximately 70% in SP-positive striosomes, 40% in SP-deficient striosomes,
      30% in the striosome-free space, and 50% in the matrix. In contrast, the
      proportion of D2 receptor-expressing, presumptive striatopallidal neurons was
      complementary to that of D1 receptor-expressing cells, indicating a close
      relationship between the map and the direct and indirect parallel circuitry.
      Finally, the most caudal part of the striatum lacked compartmentalization and
      consisted of three lamina characterized by intense and mutually exclusive
      immunoreactivities for SP and enkephalin. This tri-laminar part also received
      specific afferents from the cortex. The newly obtained map will facilitate broad
      fields of research in the basal ganglia with higher resolution of the three
      dimensional anatomy of the striatum.

PMID- 30203303
TI  - Assessment of the Dermatology Life Quality Index (DLQI) in a homogeneous
      population under lifetime arsenic exposure.
AB  - PURPOSE: The psychometric property of the Dermatology Life Quality Index (DLQI)
      is underappreciated in public health settings. Our study aimed to assess the
      reliability, validity, and measurement invariance of DLQI in a homogeneous
      population with arsenic-related skin lesions and symptoms. METHODS: A cross
      sectional study was conducted in communities under lifetime arsenic exposure. The
      DLQI was measured through a face-to-face interview. Skin examinations were
      performed by certificated dermatologists. The intensity of itching was measured
      by a numerical rating scale. Reliability, structural validity, and measurement
      invariance were determined using classical and modern test theories, including
      confirmatory factor analysis and item response models. RESULTS: 465 participants
      with arsenic-related skin lesions and symptoms completed the DLQI assessment. The
      Cronbach's alpha was 0.79, and the split-half reliability was 0.77. A two-factor
      model exhibited the best model fit among models evaluated, but local dependencies
      among items were identified. The model showed good root mean square error of
      approximation (0.031) and acceptable Tucker-Lewis index (0.92). Multi-group
      confirmatory factor analysis showed no measurement invariance across subgroups of
      age, gender, ethnicity, and intensity of itching. CONCLUSIONS: The DLQI had
      acceptable psychometric properties, but measurement invariance was not observed
      across different groups of participants.

PMID- 30203305
TI  - Activation in the auditory pathway of the gerbil studied with 18F-FDG PET:
      effects of anesthesia.
AB  - Here, we present results from an 18F-fluorodeoxyglucose (18F-FDG) positron
      emission tomography (PET) study in the Mongolian gerbil, a preferred animal model
      in auditory research. One major issue in preclinical nuclear imaging, as well as
      in most of the neurophysiological methods investigating auditory processing, is
      the need of anesthesia. We compared the usability of two types of anesthesia
      which are frequently employed in electrophysiology, ketamine/xylazine (KX), and
      fentanyl/midazolam/medetomidine (FMM), for valid measurements of auditory
      activation with 18F-FDG PET. Gerbils were placed in a sound-shielding box and
      injected with 18F-FDG. Two acoustic free-field conditions were used: (1) baseline
      (no stimulation, 25 dB background noise) and (2) 90 dB frequency-modulated tones
      (FM). After 40 min of 18F-FDG uptake, a 30 min acquisition was performed using a
      small animal PET/CT system. Blood glucose levels were measured after the uptake
      phase before scanning. Standardized uptake value ratios for relevant regions were
      determined after implementing image and volume of interest templates. Scans
      demonstrated a significantly higher uptake in the inferior colliculus with FM
      stimulation compared to baseline in awake subjects (+ 12%; p = 0.02) and with FMM
      anesthesia (+ 13%; p = 0.0012), but not with KX anesthesia. In non-auditory brain
      regions, no significant difference was detected. Blood glucose levels were
      significantly higher under KX compared to FMM anesthesia (17.29 +/- 0.42 mmol/l
      vs. 14.30 +/- 1.91 mmol/l; p = 0.024). These results suggest that valid 18F-FDG
      PET measurements of auditory activation comparable to electrophysiology can be
      obtained from gerbils during opioid-based anesthesia due to its limited effects
      on interfering blood glucose levels.

PMID- 30203306
TI  - Her ICU bed.

PMID- 30203307
TI  - Low-Cost Flexible ZnO Microwires Array Ultraviolet Photodetector Embedded in PAVL
      Substrate.
AB  - With the advent of wearable device technology, fabrication of inorganic
      semiconductor devices on flexible organic substrates is of great interest. In
      this paper, a fascinating method and a low-cost flexible substrate material
      polyvinyl alcohol (PVAL) have been utilized to embed ZnO microwire (MW) array to
      produce ultraviolet (UV) photodetector (PD) with decent photoresponsivity. The
      flexible PVAL substrate is relatively cheap and has better bendability as
      compared to polyethylene terephthalate (PET) and other traditional flexible
      substrate materials, which makes it unique in comparison to traditional devices.
      The device shows a current photoresponsivity of 29.6 A/W in the UV spectral range
      (350 to 380 nm) and maintains an excellent detection performance with even a
      bending angle of 180 degrees . In dark, a low current of 1.4 MUA at 5 V bias and
      response time of 4.27 ms was observed. In addition to the excellent device
      performance at wide bending angles, the fabricated device also performs well with
      the bending radii close to 0. Therefore, ZnO MW array PD has a great potential
      for the real-time monitoring of harmful UV exposure to warn the users for the
      appropriate arrangement avoidance.

PMID- 30203308
TI  - Enhancing Low-Intensity Coaching in Parent Implemented Early Start Denver Model
      Intervention for Early Autism: A Randomized Comparison Treatment Trial.
AB  - Short-term low intensity parent implemented intervention studies for toddlers
      with autism spectrum disorder (ASD) have found it difficult to demonstrate
      significantly improved developmental scores or autism severity compared to
      community treatment. We conducted a randomized comparative intent-to-treat study
      of a parent implemented intervention to (1) test the effects of an enhanced
      version on parent and child learning, and (2) evaluate the sensitivity to change
      of proximal versus distal measures of child behavior. We randomized 45 children
      with ASD, 12-30 months of age, into one of two versions of parent-implemented
      Early Start Denver Model (P-ESDM), the basic model, in which we delivered 1.5 h
      of clinic-based parent coaching weekly, and an enhanced version that contained
      three additions: motivational interviewing, multimodal learning tools, and a
      weekly 1.5-h home visit. We delivered the intervention for 12 weeks and measured
      child and parent change frequently in multiple settings. We found a time-by-group
      interaction: parents in the enhanced group demonstrated significantly greater
      gains in interaction skills than did parents in the non-enhanced group. Both
      interventions were associated with significant developmental acceleration;
      however, child outcomes did not differ by group. We found a significant
      relationship between degree of change in parental interaction skill and rate of
      children's improvement on our proximal measure. Parents in both groups reported
      satisfaction with the intervention. These findings suggest that parent skills
      improved more in the enhanced group than the comparison group. Children in the
      two groups showed similar improvements. Rate of individual parent learning was
      associated with greater individual child progress on a measure quite proximal to
      the treatment, though not on standardized assessments.

PMID- 30203309
TI  - Distractor Inhibition in Autism Spectrum Disorder: Evidence of a Selective
      Impairment for Individuals with Co-occurring Motor Difficulties.
AB  - Although most researchers agree that individuals with Autism Spectrum Disorder
      (ASD) exhibit atypical attention, there is little consensus on the exact nature
      of their deficits. We explored whether attentional control in ASD varies as a
      function of motor proficiency. Nineteen children with ASD and 26 typically
      developing controls completed the Movement Assessment Battery for Children and
      two ocular motor tasks requiring them to generate a saccade toward, and fixate, a
      visual target in the presence or absence of a distractor. The ASD group
      demonstrated poorer accuracy than typically-developing controls when distractors
      were present. Importantly, however, ASD symptomology was only related to poorer
      accuracy in individuals with motor difficulties. These findings suggest that
      distractor inhibition may be selectively impaired in this subgroup.

PMID- 30203310
TI  - Autistic Traits and Prosocial Behaviour in the General Population: Test of the
      Mediating Effects of Trait Empathy and State Empathic Concern.
AB  - Although the core characteristics associated with autistic traits are impaired
      social interactions, there are few studies examining how autistic traits
      translate into prosocial behaviour in daily life. The current study explored the
      effect of autistic traits on prosocial behaviour and the mediating role of
      multimodal empathy (trait empathy and state empathic concern). The results showed
      that autistic traits reduced prosocial behaviour directly and indirectly through
      complex mediation by multimodal empathy. The findings revealed the internal
      mechanism of autistic traits impeding prosocial behaviour and expanded our
      understandings of social behaviour in autism spectrum conditions (ASCs) and
      autistic traits in the general population. Furthermore, the results have
      implications for social adaptability interventions for individuals with ASCs and
      high levels of autistic traits.

PMID- 30203311
TI  - Social Stories for Children with Autism Spectrum Disorder: Validating the Content
      of a Virtual Reality Program.
AB  - Autism spectrum disorder (ASD) is a neurodevelopmental disorder that affects
      socio-emotional skills and perspective-taking abilities. Although social stories
      in a form of virtual reality program can help children with ASD, developing them
      and identifying appropriate responses might be subjective and thus challenging.
      Using Delphi method, and guided by general case training, we involved 63 parents
      and clinicians of individuals with ASD, in two rounds of online iteration to
      refine the stories. Scenarios that reached a 75% agreement level were accepted.
      This project is the first study to develop and validate a library of 75 short
      socio-emotional stories that illustrate various types and intensities of emotion
      in three social contexts of home, school, and community as the content of a
      virtual reality program.

PMID- 30203312
TI  - Frailty Status Affects the Decision for Long-Term Anticoagulation Therapy in
      Elderly Patients with Atrial Fibrillation.
AB  - BACKGROUND: Elderly patients are underrepresented in the studies concerning
      anticoagulation therapy (AT) in atrial fibrillation (AF), while patients' frailty
      status is lacking in most of the studies. OBJECTIVE: Our objective was to
      evaluate AT in AF elderly patients and study the effect of patients' frailty
      status on their long-term AT. METHODS: We conducted an observational prospective
      study that enrolled consecutive AF patients (>= 75 years) who were hospitalized
      in the Department of Internal Medicine of the University Hospital of Heraklion,
      Crete, Greece from 1 June 2015 to 1 June 2016. We recorded the AT on admission
      and at discharge, all-cause mortality, and hospital readmission in a follow-up
      period of 1 year after hospital discharge. Frailty status was assessed by pre
      established scores. RESULTS: One hundred and four consecutive patients (49% male;
      median age 87 years) were enrolled, 78 (78.8%) of whom received AT at discharge.
      Patients who did not receive AT at discharge had a higher HEMORR2HAGES (Hepatic
      or renal disease, Ethanol abuse, Malignancy, Older age, Reduced platelet count or
      function, Re-bleeding, Hypertension, Anemia, Genetic factors, Excessive fall risk
      and Stroke) score (5.5 +/- 1.15 vs. 4.79 +/- 1.68; p = 0.032), a lower Katz score
      (2.48 +/- 2.23 vs. 4.08 +/- 2.25; p = 0.006), and a higher Clinical Frailty Scale
      score (7 +/- 1.95 vs. 5.57 +/- 2.05; p = 0.006). Sixty-five patients (62.5%) were
      readmitted to a hospital during the follow-up period. In-hospital death occurred
      in five patients (4.8%) and 57 patients (57.6%) died within the follow-up period.
      CONCLUSION: A high percentage of the elderly AF patients did not receive AT, even
      at discharge. Patients who did not receive AT at discharge had higher bleeding
      and frailty scores. In the 1-year follow-up period after hospital discharge, high
      all-cause mortality and a high number of hospital readmissions were recorded.

PMID- 30203313
TI  - Factors Related to the Use of Topical vs. Oral NSAIDs for Sprains, Strains, and
      Contusions in a Senior Population: A Retrospective Analysis of Administrative
      Claims Data.
AB  - BACKGROUND: Research to date on sprains, strains, and contusions has focused
      mainly on the analysis of sports-related injuries, occupational injuries,
      injuries resulting from automobile accidents, and severe injuries that result in
      inpatient hospital stays. Little is known about real-world acute sprains,
      strains, and contusions in an aging population. Patients may be treated with over
      the-counter, oral, non-steroidal anti-inflammatory drugs (NSAIDs) for acute
      sprains, strains, and contusions or may require the use of prescription NSAIDs.
      For sprains, strains, and contusions treated with prescription NSAIDs, the choice
      of topical administration or oral administration likely depends on a number of
      factors such as age and comorbid conditions. OBJECTIVES: The objective of the
      study was to identify factors associated with the use of a prescription topical
      NSAID or a prescription oral NSAID for the treatment of sprains, strains, and
      contusions among patients aged 65-89 years enrolled in the Medicare Advantage
      with Prescription Drug plan. METHODS: The study sample was selected from the
      Humana Research Database (Louisville, KY, USA). Study subjects were identified as
      patients enrolled in Medicare Advantage with Prescription Drug plans, aged 65-89
      years, having a medical claim with an International Classification of Diseases,
      Ninth Revision, Clinical Modification indicative of an acute sprain, strain, and
      contusion between 1 January, 2010 and 31 March, 2014 (identification period). The
      date of the first claim was considered the index date, and subjects were required
      to have 12 months of continuous enrollment before the index date and a minimum of
      3 months continuous enrollment after the index date. Prescription NSAID use
      during the 3 months after the index sprain, strain, and contusion diagnosis was
      required for study inclusion and was identified based on a pharmacy claim for a
      topical or an oral NSAID. Patients with prescription NSAID use leading up to the
      sprains, strains, and contusions were excluded. Potential factors related to the
      use of a topical vs. oral NSAID were identified using stepwise logistic
      regression with backward elimination. RESULTS: After applying the inclusion and
      exclusion criteria, 42,283 patients were prescribed an oral or topical NSAID
      (39,294 oral; 2989 topical) within 3 months of the index sprain, strain, and
      contusion diagnosis. After applying stepwise logistic regression, and retaining
      variables with statistically significant parameter estimates (p < 0.05), use of
      topical NSAIDs was higher among female individuals [odds ratio and 95% confidence
      interval = 1.34 (1.24-1.45)], and appeared to increase with age [odds ratio =
      1.04 (1.04-1.05)]. Topical NSAID use was lower in the Midwest region [odds ratio
      = 0.85 (0.77-0.94)] in comparison to the Southern region. Clinical factors
      associated with topical NSAID use included Elixhauser Comorbidity Index score
      [odds ratio = 1.06 (1.04-1.09)], medication burden [odds ratio = 1.06 (1.04
      1.08), pill burden [odds ratio = 1.02 (1.01-1.03), specific comorbid conditions,
      including site-specific osteoarthritis of the upper arm [odds ratio = 2.34 (1.19
      4.60)], ankle/foot [odds ratio = 1.46 (1.14-1.87)], or lower leg [odds ratio =
      1.21 (1.07-1.36)], myofascial pain [odds ratio = 1.31 (1.21-1.42)],
      gastrointestinal/hepatic disorders [odds ratio = 1.15 (1.05-1.25)],
      systemic/central pain [odds ratio = 1.12 (1.01-1.23)], and cataracts [odds ratio
      = 1.10 (1.02-1.20)]. Conversely, a diagnosis of diabetes mellitus was related to
      use of an oral NSAID rather than a topical NSAID [odds ratio = 0.86 (0.78-0.94)].
      Diagnosis of the index sprain, strain, and contusion in an emergency department
      instead of a physician's office was also associated with oral NSAID use [odds
      ratio = 0.42 (0.37-0.47)]. CONCLUSIONS: Topical NSAIDs were used less often than
      oral NSAIDs following a sprain, strain, or contusion. Age, medication burden,
      pill burden, evidence of gastrointestinal disorder, and evidence of certain pain
      related conditions were significant factors associated with topical NSAID as
      opposed to oral NSAID use. In comparison to oral NSAIDs, topical NSAIDs were more
      likely to be prescribed in a physician's office than an emergency department,
      possibly because a patient's physician has a better understanding of the
      patient's concomitant medications and comorbidities. Although topical NSAIDs were
      more likely to be used than oral NSAIDs in patients with gastrointestinal
      disorders, the use of oral NSAIDs among patients with gastrointestinal bleeding
      was substantial.

PMID- 30203314
TI  - Efficacy and safety of mycophenolate mofetil in progressive multiple sclerosis
      patients.
AB  - OBJECTIVES: There are increasingly effective therapies for relapsing forms of
      multiple sclerosis (MS); however, the options for the progressive patient
      population are limited. The effect of mycophenolate mofetil (MMF), a disease
      modifying agent for several autoimmune diseases, in progressive MS has not been
      explored effectively. We performed a prospective study to assess the safety and
      efficacy of MMF in progressive MS patients. METHODS: We identified 64 patients
      enrolled in the comprehensive longitudinal database at the Partners MS Center,
      who fulfilled our inclusion criteria. They were exposed to MMF for at least 1
      year with recorded clinical outcomes. Efficacy was assessed by comparing the
      absolute relapse rate (ARR), and the mean Expanded Disability Status Scale (EDSS)
      and timed 25 foot walk (T25FW) test scores before and after MMF treatment.
      RESULTS: At the start of MMF, 78% of patients (n = 50) were in the 4-7.5 EDSS
      range. There was a slight increase in mean EDSS from 5.49 +/- 1.65 (n = 48) 1
      year before MMF start to 5.85 +/- 1.56 (n = 48) 1 year after (p = 0.020). The
      mean T25FW score increased 1 year before MMF from 12.3 +/- 9.6 s (n = 38) to 15.6
      +/- 12.3 s (n = 38) 1 year after (p = 0.009). The ARR in the 2 years pre-MMF
      period was 0.30 +/- 0.63, which decreased to a 0.09 +/- 0.29 (p = 0.022) 2 years
      post MMF. CONCLUSION: MMF did not affect disease progression but did influence
      relapse rate. We believe that other medication options should be considered
      before MMF in advanced progressive patients.

PMID- 30203315
TI  - Protective and therapeutic effects of exercise on stress-induced memory
      impairment.
AB  - The objective of this paper was to systematically evaluate the potential
      preventive and therapeutic effects of exercise in attenuating stress-induced
      memory impairment. A systematic review was employed, searching PubMed, PsychInfo,
      Sports Discus and Google Scholar databases. For eligibility, studies had to be
      published in English, employ an experimental design, have the acute or chronic
      bout of exercise occur prior to, during or after the stressor, implement a
      psychophysiological stressor, and have an assessment of memory function occurring
      after the stressor. In total, 23 studies were evaluated, all of which were
      conducted among animal models. All 23 studies employed a chronic exercise
      protocol and a chronic stress protocol. Eight studies evaluated a preventive
      model, three employed a concurrent model, ten studies employed a therapeutic
      model, and two studies evaluated both a preventive and therapeutic model within
      the same study. Among the eight studies employing a preventive model, all eight
      demonstrated that the stress regimen impaired memory function. In all eight of
      these studies, when exercise occurred prior to the stressor, exercise attenuated
      the stress-induced memory impairment effect. Among the ten studies employing a
      therapeutic model, one study showed that the stress protocol enhanced memory
      function, one showed that the stress protocol did not influence memory, and eight
      demonstrated that the stress regimen impaired memory function. Among the eight
      studies showing that the stress protocol impaired memory function, all eight
      studies demonstrated that exercise, after the stressor, attenuated stress-induced
      memory impairment. Within animal models, chronic stress is associated with memory
      impairment and chronic exercise has both a preventive and therapeutic effect in
      attenuating stress-induced memory impairment. Additional experimental work in
      human studies is needed. Such work should also examine acute exercise and stress
      protocols.

PMID- 30203316
TI  - Autoantibodies against dsDNA measured with nonradioactive Farr assay-an
      alternative for routine laboratories.
AB  - Autoantibodies against dsDNA are utilized for the diagnosis and prognosis of SLE
      as they are highly specific and correlate with disease activity/renal
      involvement. However, different detection methods are used in routine diagnostic
      laboratories. Farr radioimmunoassay (Farr-RIA) has been designated as the
      preferred method, since it provides very specific and at the same time
      quantitative results, enabling follow-up of level variations over time. Using
      intercalating fluorescent dsDNA dye would enable all the benefits of Farr-RIA
      without the radioactive material and organic solvents. To develop a modified
      fluorescent Farr method (Farr-FIA) and compare it to the classical Farr-RIA in
      regard to laboratory parameters, as well as clinical utility. Assays were tested
      on sera of 70 SLE patients, 78 other autoimmune patients, and 145 healthy blood
      donors. DNA for Farr-FIA was isolated from healthy donor, for Farr-RIA, 14C
      labeled dsDNA from E. coli was used and mixed with sera in borate-buffered
      saline, followed by precipitation with saturated ammonium sulfate solution and
      centrifugation. The supernatant (S) was separated from the precipitate (P), and
      content of dsDNA was measured with PicoGreen (Invitrogen) in Farr-FIA or
      radioactive isotope in scintillation solution in Farr-RIA. The results were
      calculated as a ratio (P-S)/(P+S). Farr-FIA has a diagnostic sensitivity of 53%
      and diagnostic specificity of 100% (ROC AUC 0.781). Good correlation and
      agreement were shown between Farr-RIA and Farr-FIA. Also, there is good
      correlation between Farr-FIA and SLEDAI, comparable to that of Farr-RIA. Farr-FIA
      differs from Farr-RIA in the changed detection system yielding comparable results
      and thus could represent a nonradioactive replacement for Farr-RIA.

PMID- 30203317
TI  - Complement your knowledge with a rare cause of pauci-immune glomerulonephritis.
AB  - RPGN can be subdivided into three categories on an immunopathologic basis: pauci
      immune glomerulonephritis (PIGN), anti-glomerular basement membrane
      glomerulonephritis (anti-GBM disease), or immune complex-mediated
      glomerulonephritis (GN). PIGN is the most common cause of RPGN (80% of cases).
      The most common etiology of PIGN is anti-neutrophil cytoplasmic antibody (ANCA)
      associated GN, which accounts for up to 90% of PIGN. PIGN is unique in that few
      to no immunoglobulin deposits are seen on glomerular immunofluorescence (IF) and
      electron microscopy (EM), but it is important to remember that dysregulation of
      the alternative pathway may result in the deposition of complements leading to
      inflammatory injury even in PIGN. Membranoproliferative glomerulonephritis (MPGN)
      is a rare, primary glomerular disorder. Both ANCA-associated GN and complement
      mediated MPGN will lack immunoglobulin staining on immunofluorescence (IF) and
      thus present as PIGN on pathologic examination. This may lead to occurrences
      where these entities mimic one another, therefore necessitating heightened
      suspicion and close pathologic examination of a renal biopsy with electron
      microscopy to differentiate the diagnoses. This case highlights a rare case of C3
      GN mimicking ANCA-associated GN.

PMID- 30203318
TI  - Central Nervous System Prophylaxis Strategies in Diffuse Large B Cell Lymphoma.
AB  - OPINION STATEMENT: Central nervous system (CNS) relapse is an undesirable event
      in the course of patients with diffuse large B cell lymphoma (DLBCL) with a
      median survival of approximately 6 months following CNS relapse. CNS prophylaxis
      for the prevention of CNS recurrence, in addition to the standard R-CHOP
      chemotherapy, is thus preferable. For an overall relapse risk of 2-5%,
      administration of CNS-directed therapies for all patients with DLBCL is
      unnecessary and prophylaxis should be targeted for the high-risk patients. CNS
      International Prognostic Index (CNS-IPI) score has enabled risk stratification
      with risk ranging < 1% (low-risk group) compared to > 10% (high-risk group). The
      latter could be considered for CNS prophylaxis. CNS-IPI, however, is not perfect
      and may not capture patients with high-risk extra-nodal sites such as testicular
      DLBCL. Cell-of-origin and MYC/BCL2 expression can further build on CNS-IPI to
      narrow higher risk patients. CNS prophylaxis strategies are controversial. Common
      strategies include intrathecal (IT) chemotherapy and systemic CNS penetrants such
      as methotrexate. IT chemotherapy does not adequately penetrate the brain
      parenchyma and hence it is insufficient in preventing parenchymal CNS
      recurrences. Most experts promote systemic methotrexate for high-risk groups,
      which penetrates both the leptomeningeal and parenchymal CNS compartments. Even
      though systemic CNS prophylaxis is widely promoted over IT alone, its efficacy is
      unclear. Ongoing efforts in search for appropriate CNS prophylaxis strategies are
      warranted. My personal practice is to administer systemic high-dose methotrexate
      in conjunction with R-CHOP chemotherapy for eligible patients deemed at a high
      risk of CNS recurrence, especially those with high-risk CNS-IPI and extra-nodal
      involvement.

PMID- 30203319
TI  - Impact of sphincter lesions and delayed sphincter repair on sacral
      neuromodulation treatment outcomes for faecal incontinence: results from a
      Finnish national cohort study.
AB  - PURPOSE: The aim of this multicentre study was to analyse the effects of patent
      sphincter lesions and previous sphincter repair on the results of sacral
      neuromodulation (SNM) treatment on patients with faecal incontinence (FI).
      METHODS: Patients examined by endoanal ultrasound (EAUS) with FI as the
      indication for SNM treatment were included in the study. Data was collected from
      all the centres providing SNM treatment in Finland and analysed for differences
      in treatment outcomes. RESULTS: A total of 237 patients treated for incontinence
      with SNM had been examined by EAUS. Of these patients, 33 had a history of
      previous delayed sphincter repair. A patent sphincter lesion was detected by EAUS
      in 128 patients. The EAUS finding did not influence the SNM test phase outcome (p
      = 0.129) or the final treatment outcome (p = 0.233). Patient's history of prior
      sphincter repair did not have a significant effect on the SNM test (p = 0.425) or
      final treatment outcome (p = 0.442). CONCLUSIONS: Results of our study indicate
      that a sphincter lesion or previous sphincter repair has no significant effect on
      the outcome of SNM treatment. Our data suggests that delayed sphincter repair
      prior to SNM treatment initiation for FI is not necessary.

PMID- 30203320
TI  - Silver/silver chloride nanoparticles inhibit the proliferation of human
      glioblastoma cells.
AB  - Glioblastomas (GBM) are aggressive brain tumors with very poor prognosis. While
      silver nanoparticles represent a potential new strategy for anticancer therapy,
      the silver/silver chloride nanoparticles (Ag/AgCl-NPs) have microbicidal
      activity, but had not been tested against tumor cells. Here, we analyzed the
      effect of biogenically produced Ag/AgCl-NPs (from yeast cultures) on the
      proliferation of GBM02 glioblastoma cells (and of human astrocytes) by automated,
      image-based high-content analysis (HCA). We compared the effect of 0.1-5.0 ug mL
      1 Ag/AgCl-NPs with that of 9.7-48.5 ug mL-1 temozolomide (TMZ, chemotherapy drug
      currently used to treat glioblastomas), alone or in combination. At higher
      concentrations, Ag/AgCl-NPs inhibited GBM02 proliferation more effectively than
      TMZ (up to 82 and 62% inhibition, respectively), while the opposite occurred at
      lower concentrations (up to 23 and 53% inhibition, for Ag/AgCl-NPs and TMZ,
      respectively). The combined treatment (Ag/AgCl-NPs + TMZ) inhibited GBM02
      proliferation by 54-83%. Ag/AgCl-NPs had a reduced effect on astrocyte
      proliferation compared with TMZ, and Ag/AgCl-NPs + TMZ inhibited astrocyte
      proliferation by 5-42%. The growth rate and population doubling time analyses
      confirmed that treatment with Ag/AgCl-NPs was more effective against GBM02 cells
      than TMZ (~ 67-fold), and less aggressive to astrocytes, while Ag/AgCl-NP + TMZ
      treatment was no more effective against GBM02 cells than Ag/AgCl-NPs monotherapy.
      Taken together, our data indicate that 2.5 ug mL-1 Ag/AgCl-NPs represents the
      safest dose tested here, which affects GBM02 proliferation, with limited effect
      on astrocytes. Our findings show that HCA is a useful approach to evaluate the
      antiproliferative effect of nanoparticles against tumor cells.

PMID- 30203321
TI  - Cervical Lymph Node Fine-Needle Aspiration and Needle-Wash Thyroglobulin Reflex
      Test for Papillary Thyroid Carcinoma.
AB  - Fine-needle aspiration (FNA) cytology coupled with needle-wash thyroglobulin (FNA
      Tg) testing is recommended for cervical lymph node (LN) biopsies in patients with
      a history of papillary thyroid carcinoma (PTC). However, the procedure has not
      been standardized with the assay for FNA-Tg testing. A standard operating
      procedure (SOP) has been generated at our facility for cervical LN FNAs with Tg
      reflex testing on patients with a history of PTC. The procedure requires FNA
      cytology to be reviewed first, and all cases not positive for PTC are reflexed
      for FNA-Tg testing with the Beckman Access thyroglobulin assay. The thyroglobulin
      cutoff value is <= 1.0 ng/mL. From 2016 to 2017, 117 patients, including 71 women
      and 46 men, were identified as having a history of PTC. Patients' clinical
      characteristics were collected from medical records. A total of 143 LN biopsies
      were investigated for these patients. The results show that four out of 11
      (36.4%) non-diagnostic LNs and five out of five (100%) atypical/suspicious LNs
      tested positive for FNA-Tg. Among these nine patients with positive thyroglobulin
      testing, LN metastases were proven histologically for all nine patients, and two
      patients were treated with LN ablation. Out of 68 LNs positive for PTC, three had
      FNA-Tg results. FNA-Tg testing was ordered for unknown reasons on two positive
      LNs (> 5000 ng/mL thyroglobulin) from one patient. The third LN was tested due to
      non-classic morphology, and the result was less than the cutoff value. Three
      patients with negative LN biopsies were tested to have elevated (> 1.0 ng/mL)
      thyroglobulin levels. One patient (FNA-Tg ng/mL) was proven to have multiple
      metastatic LNs through follow-up surgery. However, no positive LN was identified
      for the other two patients who had FNA-Tg level of 4.1 ng/mL and 37 ng/mL
      respectively. This is likely due to contamination, as these two patients had
      intact thyroids. In our practice, the FNA-Tg test is a very useful adjunct test
      to LN FNA specimens with a non-positive diagnosis in patients with a history of
      PTC. Furthermore, FNA-Tg testing increases diagnostic sensitivity among non
      diagnostic and atypical/suspicious LNs. However, FNA-Tg testing should not
      substitute conventional cytology due to the following reasons: (1) false-negative
      thyroglobulin lab results; (2) PTC with loss of thyroglobulin expression; (3) LN
      metastasis from other origins; and (4) false-positive thyroglobulin testing due
      to blood contamination in patients who are not completely athyrotic.

PMID- 30203323
TI  - Overexpressed TTC3 Protein Tends to be Cleaved into Fragments and Form Aggregates
      in the Nucleus.
AB  - Human tetratricopeptide repeat domain 3 (TTC3) is a gene on 21q22.2 within the
      Down syndrome critical region (DSCR). Earlier studies suggest that TTC3 may be an
      important regulator in individual development, especially in neural development.
      As an E3 ligase, TTC3 binds to phosphorylated Akt and silence its activity via
      proteasomal cascade. Several groups also reported the involvement of TTC3 in
      familial Alzheimer's disease recently. In addition, our previous work shows that
      TTC3 also regulates the degradation of DNA polymerase gamma and over-expressed
      TTC3 protein tends to form insoluble aggregates in cells. In this study, we focus
      on the solubility and intracellular localization of TTC3 protein. Over-expressed
      TTC3 tends to form insoluble aggregates over time. The proteasome inhibitor MG132
      treatment resulted in more TTC3 aggregates in a short period of time. We fused
      the fluorescent protein to either terminus of the TTC3 protein and found that the
      intracellular localization of fluorescent signals are different between the N
      terminal tagged and C-terminal tagged proteins. Western blotting revealed that
      the TTC3 protein is cleaved into fragments of different sizes at multiple sites.
      The N-terminal sub-fragments of TTC3 are prone to from nuclear aggregates and the
      TTC3 nuclear import is mediated by signals within the N-terminal 1 to 650
      residues. Moreover, over-expressed TTC3 induced a considerable degree of
      cytotoxicity, and its N-terminal sub-fragments are more potent inhibitors of cell
      proliferation than full-length protein. Considering the prevalent proteostasis
      dysregulation in neurodegenerative diseases, these findings may relate to the
      pathology of such diseases.

PMID- 30203322
TI  - Genetic diversity and antimicrobial activity of lactic acid bacteria in the
      preparation of traditional fermented potato product 'tunta'.
AB  - Fermentation microorganisms, lactic acid bacteria (LAB) and yeast from 12 samples
      of tunta production chain were quantified, from the native potatoes used by the
      process fermentation of potatoes in the river up to the final product. During
      fermentation, the LAB population steadily increased from 3 to 4 to 8 log CFU/g
      during the first 8 days in the river and the yeast population increased from 2 to
      3 to 3-4 log CFU/g. Overall, 115 LAB strains were isolated using a culture
      dependent method. Molecular techniques and 16S rRNA gene sequencing enabled the
      identification of native species. In LAB isolates, members of the
      Lactobacillaceae (64%), Leuconostocaceae (9%) and Enterococcaceae (2%) families
      were identified. The most prevalent LAB species in the tunta production chain was
      Lactobacillus curvatus, followed by Leuconostoc mesenteroides and Lactobacillus
      sakei, Lactobacillus brevis and Enterococcus mundtii were also present. Only 13
      LAB strains showed anti-listerial activity, and one of them, identified as En.
      mundtii DSM 4838T [MG031213], produced antimicrobial compounds that were
      determined to be proteins after treatment with proteolytic enzymes. Based on
      these results, we suggest that traditional fermented product-derived LAB strains
      from specific environments could be selected and used for technological
      application to control pathogenic bacteria and naturally protect food from post
      harvest deleterious microbiota.

PMID- 30203324
TI  - Correction to: The Association Between Depression, Suicidal Ideation and
      Psychological Strains in College Students: A Cross-National Study.
AB  - The original version of the article unfortunately contained an error in
      acknowledgement section. The corrected acknowledgement is: This research was
      supported by a grant of Beijing Natural Science Foundation (9174046), for which
      the first author is PI.

PMID- 30203325
TI  - The transcription factor OsbHLH035 mediates seed germination and enables seedling
      recovery from salt stress through ABA-dependent and ABA-independent pathways,
      respectively.
AB  - BACKGROUND: Many transcription factors (TFs), such as those in the basic helix
      loop-helix (bHLH) family, are important for regulating plant growth and plant
      responses to abiotic stress. The expression of OsbHLH035 is induced by drought
      and salinity. However, its functional role in rice growth, development, and the
      salt response is still unknown. RESULTS: The bHLH TF OsbHLH035 is a salt-induced
      gene that is primarily expressed in germinating seeds and seedlings. Stable
      expression of GFP-fused OsbHLH035 in rice transgenic plants revealed that this
      protein is predominantly localized to the nucleus. Osbhlh035 mutants show delayed
      seed germination, particularly under salt-stress conditions. In parallel,
      abscisic acid (ABA) contents are over-accumulated, and the expression of the ABA
      biosynthetic genes OsABA2 and OsAAO3 is upregulated; furthermore, compared with
      that in wild-type (WT) seedlings, the salt-induced expression of OsABA8ox1, an
      ABA catabolic gene, in germinating Osbhlh035 mutant seeds is downregulated.
      Moreover, Osbhlh035 mutant seedlings are unable to recover from salt-stress
      treatment. Consistently, sodium is over-accumulated in aerial tissues but
      slightly reduced in terrestrial tissues from Osbhlh035 seedlings after salt
      treatment. Additionally, the expression of the sodium transporters OsHKT1;3 and
      1;5 is reduced in Osbhlh035 aerial and terrestrial tissues, respectively.
      Furthermore, genetic complementation can restore both the delayed seed
      germination and the impaired recovery of salt-treated Osbhlh035 seedlings to
      normal growth. CONCLUSION: OsbHLH035 mediates seed germination and seedling
      recovery after salt stress relief through the ABA-dependent and ABA-independent
      activation of OsHKT pathways, respectively.

PMID- 30203326
TI  - Are morphologic and topographic alterations of the mandibular fossa after fixed
      functional treatment detectable on tomograms? Visual classification and
      morphometric analysis.
AB  - AIM: The goal was to evaluate if changes in morphology and topography of the
      mandibular fossa after Functional Mandibular Advancer (FMA) treatment are
      detectable on tomograms. Furthermore, the suitability of digital tomograms (DT)
      over magnetic resonance imaging (MRI) for this particular question was
      investigated. MATERIALS AND METHODS: In all, 25 patients (14 female, 11 male)
      with a skeletal class II malocclusion received treatment with a FMA. DTs were
      available prior to (T1) and after (T2) FMA treatment. A total of 50
      temporomandibular joints were investigated. The mandibular fossae were evaluated
      metrically and visually regarding treatment-induced alterations. A p < 0.05 was
      set as the level for statistical significance for all tests. Results were
      compared to the results of a recent MRI study. RESULTS: Visual inspection of all
      50 joints in the DT at T1 and T2 revealed no alterations of the fossa shape in
      the sagittal plane; 24 patients showed identical morphology of right and left
      joints. The metrical analysis revealed no significant changes regarding width,
      depth and ratio thereof between T1 and T2. There also were no bilateral
      differences. Another 18 different distance measurements between porion,
      mandibular fossa, articular eminence and pterygoid fossa showed no significant
      changes. There was no detectable proof of a fossa shift. CONCLUSIONS: No changes
      in the sagittal plane, mandibular fossa, the articular tubercle, or a possible
      fossa shift were found in the DT of class II patients after FMA treatment. DT and
      MRI measurements and the visual inspection revealed identical findings; thus, DT
      appears to be a valuable research tool for sagittal analysis of mandibular fossa
      changes.

PMID- 30203327
TI  - Clinical Implications of the STAR*D Trial.
AB  - This chapter provides a synopsis of the clinically relevant findings derived from
      the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study and
      selected ancillary studies appended to the primary trial. The chapter describes
      the participants, their recruitment and treatment, and the study design, primary
      outcomes, and clinically informative results. In particular, the chapter
      describes acute phase response and remission rates from each of the five
      treatment steps which entail antidepressant monotherapies and combinations, and
      psychotherapy alone or in combination with an antidepressant. In addition, longer
      term outcomes beyond the 12 week acute trial are described for each treatment
      step. The treatment challenges described include patient retention and relapse,
      and longer-term follow-up. The chapter discusses the use of measurement-based
      care for delivering high-quality care, describes "treatment-resistant" depression
      and discusses its implications for clinical practice, and discusses the
      contributions of STAR*D to patient-oriented research and patient care.

PMID- 30203328
TI  - Brown Adipose Tissue Development and Metabolism.
AB  - Brown adipose tissue is well known to be a thermoregulatory organ particularly
      important in small rodents and human infants, but it was only recently that its
      existence and significance to metabolic fitness in adult humans have been widely
      realized. The ability of active brown fat to expend high amounts of energy has
      raised interest in stimulating thermogenesis therapeutically to treat metabolic
      diseases related to obesity and type 2 diabetes. In parallel, there has been a
      surge of research aimed at understanding the biology of rodent and human brown
      fat development, its remarkable metabolic properties, and the phenomenon of white
      fat browning, in which white adipocytes can be converted into brown like
      adipocytes with similar thermogenic properties. Here, we review the current
      understanding of the developmental and metabolic pathways involved in forming
      thermogenic adipocytes, and highlight some of the many unknown functions of brown
      fat that make its study a rich and exciting area for future research.

PMID- 30203330
TI  - Idarucizumab for Reversal of Dabigatran: Single-Center Real-World Experience.
AB  - BACKGROUND: Idarucizumab is used to reverse the effects of dabigatran.
      Information on the use of idarucizumab in the clinical setting remains very
      limited. OBJECTIVE: The objective of this study was to describe clinical
      experience with idarucizumab in a large medical teaching center in the USA.
      METHODS: Patients who received idarucizumab to reverse the effects of dabigatran
      between 1 January 2016 and 30 June 2018 were studied. In patients with major
      bleeding, the efficacy of idarucizumab was assessed using criteria of the
      International Society of Thrombosis and Hemostasis Scientific and Standardization
      Subcommittee. The course of treatment and clinical outcomes in patients who
      received idarucizumab for emergency surgery or procedures are described. RESULTS:
      In total, 13 patients received idarucizumab for atrial fibrillation during the
      study period. Their mean age was 77.5 +/- 7.1 years, and 12 (92.3%) were men.
      Idarucizumab was used in 11 patients for major bleeding events and in two
      patients for emergency surgery or procedures. Intracranial hemorrhage (n = 6) and
      gastrointestinal bleed (n = 2) were the most common types of bleeding. Clinical
      hemostasis was achieved in 8 of 11 (72.7%) patients with major bleeding. One
      patient with acute kidney injury needed two doses of the reversal agent to
      achieve hemostasis. One patient underwent open heart surgery and developed
      postoperative hemorrhage despite receiving idarucizumab. None of the patients
      experienced thrombotic complications or side effects that could be attributed to
      idarucizumab. CONCLUSION: Real-world experience in a US hospital with the use of
      idarucizumab in emergency situations requiring the reversal of the effects of
      dabigatran is described. Idarucizumab represents an exciting new antidote for
      dabigatran, but clinical efficacy and cost-effectiveness data remain lacking.

PMID- 30203331
TI  - Synthesis and In Vitro Study of a Dual-Mode Probe Targeting Integrin alphavbeta3.
AB  - Malignant tumors constitute a serious disease that threaten human life, and early
      diagnosis and metastasis prediction are critical to the choice of treatment plan
      and the timing of treatment. Integrin alphavbeta3, which has received broad
      attention as a molecular marker of the tumor neovasculature, is an important
      target for monitoring tumorigenesis and progression in molecular imaging
      research. This study reports a magnetic resonance (MR)/fluorescence dual-mode
      molecular probe, cRGD-Gd-Cy5.5, which targets the integrin alphavbeta3 receptor
      and uses liposomes as carrier. The obtained nanoprobe had a size of 60.08 +/-
      0.45 nm, with good dispersion in water, a uniform distribution of sizes,
      desirable stability, and high relaxivity. Its r1 relaxation rate was 10.515 mM-1
      s-1, much higher than that of other Gd chelates in clinical use. The probe showed
      no cytotoxicity at the tested concentrations in vitro, and its ability to target
      A549 cells and SUNE-1-5-8F cells was preliminarily evaluated through in vitro
      fluorescence imaging and MR imaging. The results demonstrated that the cRGD-Gd
      Cy5.5 nanoprobe had good characteristics, showing desirable stability and
      biosafety, a high T1 relaxation rate, and strong targeting and binding to tumors
      with high expression of integrin alphavbeta3. Therefore, cRGD-Gd-Cy5.5 is a
      promising agent for the visual monitoring of tumor metastasis.

PMID- 30203329
TI  - [Central venous pressure in liver surgery : A primary therapeutic goal or a
      hemodynamic tessera?]
AB  - Central venous pressure (CVP) is deemed to be an important parameter of
      anesthesia management in liver surgery. To reduce blood loss during liver
      resections, a low target value of CVP is often propagated. Although current meta
      analyses have shown a connection between low CVP and a reduction in blood loss,
      the underlying studies show methodological weaknesses and advantages with respect
      to morbidity and mortality can hardly be proven. The measurement of the CVP
      itself is associated with numerous limitations and influencing factors and the
      measures to reduce the CVP have been insufficiently investigated with respect to
      hepatic hemodynamics. The definition of a generally valid target area for the CVP
      must be called into question. The primary objective is to maintain adequate
      oxygen supply and euvolemia. The CVP should be regarded as a mosaic stone of
      hemodynamic management.

PMID- 30203332
TI  - Prevalence of Clostridium Difficile-Associated Diarrhoea in Hospitalised Patients
      (Results of a Russian Prospective Multicentre Study).
AB  - INTRODUCTION: The objective of the study was to evaluate the prevalence of
      Clostridium difficile-associated diarrhoea (CDAD) among hospitalised patients
      with antibiotic-associated diarrhoea (AAD) in general and by specific types of
      medical care and hospital units. METHODS: A prospective, cross-sectional, non
      interventional, multicentre study. The main inclusion criteria were: patient age
      >= 18 years, hospital stay of at least 48 h, current antibiotic therapy or
      antibiotic therapy within the previous 30 days, loose stools (Bristol stool types
      5-7 and stool frequency >= 3 within <= 24 consecutive hours or exceeding normal
      for the patient) and signed informed consent form. The stool sample was taken to
      the local (study site) microbiology laboratory for detection of glutamate
      dehydrogenase (GDH) and toxins A/B using enzyme immunoassay (EIA) stool test.
      RESULTS: From April 2016 to April 2017, a total of 1245 patients from 12 large
      hospitals were enrolled in the study. Data on 81 patients were excluded from the
      analysis for different reasons. Data on 1164 patients (45.2% males and 54.8%
      females) with a mean age of 54.9 years (range 18-95 years) were analysed. Length
      of hospitalisation was 2-188 days (median, 8 days). The EIA stool test showed
      CDAD-positive results in 21.7% (253/1164) patients. The patients were from
      surgery units (546/1164), internal medicine units (510/1164) and intensive care
      units (108/1164). The prevalence of CDAD among patients from surgery, internal
      medicine and intensive care units was 26.2, 17.8 and 17.6%, respectively.
      Oncology, gastroenterology, septic surgery, oncohaematology and general medical
      hospital units accounted for more than 75% of all patients included; the
      prevalence of CDAD by those hospital units was 11.3, 15.0, 39.2, 17.6, and 27.2%,
      respectively. The proportion of GDH-positive and toxin A/B-negative patients by
      the rapid stool test result was 16.8% (196/1164). The prevalence of CDAD varied
      widely between the hospitals (from 0 to 44.3%). CONCLUSIONS: The prevalence of
      CDAD among hospitalised patients with AAD in this study was 21.7% (95% confidence
      interval: 14.8 and 28.7%). The percentage of CDAD varied widely between hospitals
      and by specific types of medical care and hospital units.

PMID- 30203334
TI  - Platelet-Rich Plasma: Review of Current Literature on its Use for Tendon and
      Ligament Pathology.
AB  - PURPOSE OF REVIEW: Platelet-rich plasma (PRP) contains numerous growth factors
      and cytokines that potentially offer an alternative treatment modality to assist
      in the healing of multiple musculoskeletal issues. The purpose of this review was
      to examine the latest literature on the use of PRP for various ligament and
      tendon pathologies. RECENT FINDINGS: Recent literature has shown moderate- to
      high-quality evidence that PRP can have positive clinical effects in certain
      conditions such as lateral epicondylitis and rotator cuff tendinopathy.
      Prospective studies have shown that it can also be useful in the treatment of
      patella tendinopathy. In summary, we found PRP to have variable success in
      ligament and tendon pathology; however, it should be considered a viable option
      in chronic musculoskeletal disease that has failed other treatments. Patient
      selection, duration of symptoms, and combining with other modalities such as
      physical therapy should all be taken into consideration in treatment with PRP.

PMID- 30203335
TI  - A monocentric retrospective study of 138 therapy-related myeloid neoplasms.
AB  - As diagnosing therapy-related myeloid neoplasms (t-MN) is often challenging, we
      reviewed clinicopathological features of t-MN patients. Medical records of 138
      patients, diagnosed with t-MN between 1995 and 2017, were reviewed. Of 138
      patients, 80 had t-MDS, 53 t-AML, and 5 t-MDS/MPN (age, 22-88 years; median 64
      years; male/female ratio, 0.8). The median latency time was 6 years and 5 months.
      Of 115 patients, 56 patients received cytotoxic-/radiotherapy for a solid tumor,
      56 for hematological malignancy, and 3 for an auto-immune disorder, respectively.
      Another 21 patients had a combination of 2 disorders. Moreover, 2 patients had 3
      previous malignancies. Breast cancer was the most prevalent tumor, followed by
      low-grade B non-Hodgkin lymphoma. Immunophenotyping and immunohistochemistry
      showed aberrant expression of B-, T-, or NK-cell markers in 21% and 6%,
      respectively. In 90% of the patients, dysplasia in >= 1 lineage was found. KMT2A
      fusion gene transcripts were seen in 5%. Cytogenetic analysis showed complex
      karyotypes (31%) and chromosome 5 and/or 7 abnormalities (40%). Almost 82% of the
      patients died and the median overall survival was about 1 year. Our study
      confirms that previous therapy for breast cancer is the most important cause of t
      MN. KMT2A fusion genes are prevalent and complex karyotypes and/or chromosomes 5
      and/or 7 abnormalities are common.

PMID- 30203333
TI  - Platelet-Rich Plasma and Cartilage Repair.
AB  - PURPOSE OF REVIEW: To assess the utilization and efficacy of platelet-rich plasma
      (PRP), for the treatment of articular cartilage injury, most commonly
      characterized by progressive pain and loss of joint function in the setting of
      osteoarthritis (OA). RECENT FINDINGS: PRP modulates the inflammatory and
      catabolic environment through a locally applied concentrate of platelets,
      leukocytes, and growth factors. Clinically, PRP has been shown to be possibly a
      viable treatment adjuvant for a variety of inflammatory and degenerative
      conditions. Recent efforts have focused on optimizing delivery methods that
      enable platelets to slowly degranulate their biological constituents, which may
      promote healing and improve OA symptoms for a longer duration. There are various
      factors that affect the progression of OA within joints, including inhibition of
      inflammatory cytokines and altering the level of enzymatic expression. PRP
      therapy aims to mediate inflammatory and catabolic factors in a degenerative
      environment through the secretion of anti-inflammatory factors and chemotaxic
      effects. There are a growing number of studies that have demonstrated the
      clinical benefit of PRP for non-operative management of OA. Additional randomized
      controlled trials with long-term follow-up are needed in order to validate PRP's
      therapeutic efficacy in this setting. Additionally, continued basic research
      along with well-designed pre-clinical studies and reporting standards are
      necessary in order to clarify the effectiveness of PRP for cartilage repair and
      regeneration for future clinical applications.

PMID- 30203337
TI  - Soluble Compounds of Filamentous Fungi Harm the Symbiotic Fungus of Leafcutter
      Ants.
AB  - Chemical compounds are key to understand symbiotic interactions. In the
      leafcutter ant-microbe symbiosis a plethora of filamentous fungi continuously
      gain access the ant colonies through plant substrate collected by workers. Many
      filamentous fungi are considered transient in attine ant colonies, however, their
      real ecological role in this environment still remains unclear. A possible role
      of these microorganisms is the antagonism towards Leucoagaricus gongylophorus,
      the mutualistic fungus that serve as food for several leafcutter ant species.
      Here, we showed the antagonism of filamentous fungi isolated from different
      sources, and the negative impacts of their metabolites on the growth of the ant
      fungal cultivar. Our results demonstrate that the chemical compounds produced by
      filamentous fungi can harm the mutualistic fungus of leafcutter ants.

PMID- 30203339
TI  - Urologic Management of the Spinal Cord Injured Patient.

PMID- 30203336
TI  - Understanding the relationship between cognition and death: a within cohort
      examination of cognitive measures and mortality.
AB  - Despite several studies demonstrating an independent and inverse association
      between cognition and mortality, the nature of this association still remains
      unclear. To examine the association of cognition and mortality after accounting
      for sociodemographic, health and lifestyle factors and to explore both test and
      population characteristics influencing this relationship. In a population based
      cohort of 8585 men and women aged 48-92 years, who had cognitive assessments in
      2006-2011 and were followed up till 2016 for mortality, we examined the
      relationship between individual cognitive tests as well as a global cognition
      score to compare their ability in predicting mortality and whether these differed
      by population characteristics. Risk of death was estimated using Cox proportional
      hazard regression models including sociodemographic, lifestyle and health
      variables, and self-reported comorbidities, as covariates in the models. Poor
      cognitive performance (bottom quartile of combined cognition score) was
      associated with higher risk of mortality, Hazard Ratio = 1.32 (95% Confidence
      Interval 1.09, 1.60); individual cognitive tests varied in their mortality
      associations and also performed differently in middle-age and older age groups.
      Poor cognitive performance is independently associated with higher mortality.
      This association is observed for global cognition and for specific cognitive
      abilities. Associations vary depending on the cognitive test (and domain) as well
      as population characteristics, namely age and education.

PMID- 30203338
TI  - How to prevent dislocation after revision total hip arthroplasty: a systematic
      review of the risk factors and a focus on treatment options.
AB  - BACKGROUND: Dislocation represents the most common complication after revision
      total hip arthroplasty (rTHA). Understanding risk factors for dislocation has a
      great clinical relevance for every hip surgeon in order to consider all surgical
      options for effective planning. The aim of this systematic review was to answer
      two main questions-(1) what are the risk factors for instability after rTHA? and
      (2) what are the best preoperative assessments and surgical options to avoid
      dislocation after rTHA? MATERIALS AND METHODS: Scientific databases were accessed
      to identify papers dealing with prevention and treatment of dislocation after
      rTHA. We performed a search using the keywords 'revision hip arthroplasty' and
      'dislocation', 'instability', 'outcome', 'failure', 'treatment'. After removal of
      duplicates and exclusion of works published in different languages, 33 articles
      were reviewed completely. RESULTS: Risk factors were analysed in order to
      establish the most relevant and evidence-based treatments available in the
      current literature. CONCLUSIONS: The risk of dislocation after rTHA can be
      reduced using some precautions inferred from the literature. The use of a larger
      femoral and acetabular component, elevated rim liner and dual mobility implants
      can significantly reduce the risk of dislocation after rTHA. However, care must
      be taken regarding patient-related risk factors since these cannot be addressed
      and modified. Hence, a complete evaluation of risk factors should be performed
      for each patient and procedure before starting rTHA.

PMID- 30203340
TI  - Inferring bladder cancer research prioritization from patient-generated online
      content.
AB  - PURPOSE: Patients and their families utilize online resources when dealing with a
      diagnosis of bladder cancer. Many patients have questions regarding clinical
      management options. Online research forums may help researchers and providers
      identify research areas of interest. Our objective was to review online forums
      and identify research questions that are important to patients and families
      impacted by bladder cancer diagnosis. METHODS: We reviewed 1 month of online
      content from the Bladder Cancer Advocacy Network Inspire online community (
      https://www.inspire.com/groups/bladder-cancer-advocacy-network ). Using affinity
      diagramming, we categorized the submitted content from patient users into themes
      stratified by the cancer severity of the patient user (non-muscle-invasive
      bladder cancer, muscle-invasive bladder cancer, metastatic bladder cancer). We
      categorized the content by the audience of forum posts (i.e., inwardly directed,
      those seeking support, vs. outwardly directed, those sharing personal
      experiences) and constructed comparative effectiveness research questions from
      the submitted content. RESULTS: From 14 July 2014 to 14 August 2014, a total of
      394 forum posts were collected, of which 3 were excluded from analysis due to non
      relevant content, leaving 391 comments for final analysis. Almost 38% of posts
      involved muscle-invasive bladder cancer and 25% of posts were from people other
      than the patient. Inwardly and outwardly directed posts were commonly related to
      clinical treatment concerns. CONCLUSIONS: Review of online patient-generated
      content may offer insight into comparative effectiveness research topics of
      importance to bladder cancer patients. A more formalized process may better
      represent research priorities among bladder cancer patients.

PMID- 30203342
TI  - Detection of Influenza in the Epidemic Season 2016/2017 Based on I-MOVE+ Project.
AB  - In the influenza season 2016/2017 in Europe, the predominant virus was A/H3N2/.
      In Poland, the percentage of people vaccinated against influenza was 3.33%.
      European I-MOVE+ project shows how important it is to monitor the effectiveness
      of influenza vaccine. The project demonstrates that a match between the
      circulating vaccine strains and those included in the vaccine for the Northern
      Hemisphere was low-to-moderate. In the present study, there were 379 patients and
      296 control subjects examined in hospitals in Poland as part of I-MOVE+ project.
      The real-time reverse transcription polymerase chain reaction (qRT-PCR) method
      was used to detect the influenza virus in all subjects. We detected the influenza
      subtype A/H3N2/ in 59.1% and type B virus in 2.1%. There was one co-infection of
      subtype A/H3N2/ with subtype A/H1N1/ and eight co-infections of type B with
      subtype A/H3N2/. No influenza viruses were detected in the control group. Only 19
      patients and 22 control subjects were vaccinated during the epidemic season in
      question. A proportion of people vaccinated against influenza in Poland remains
      dismally low compared to other European countries.

PMID- 30203341
TI  - High rate of occult cancer found in prophylactic mastectomy specimens despite
      thorough presurgical assessment with MRI and ultrasound: findings from the
      Hereditary Breast and Ovarian Cancer Registration 2016 in Japan.
AB  - PURPOSE: Prophylactic surgery is a preemptive strategy for hereditary breast and
      ovarian cancer (HBOC). Prophylactic mastectomy (PM) reduces breast cancer risk by
      > 90%. The aim of our study is to analyze the information of the Japanese
      pedigrees and to utilize the results for clinical practice. METHODS: We
      statistically analyzed records of HBOC registrees who had undergone BRCA1/2
      genetic testing at seven medical institutions up until 2016. In the cases of PM,
      we examined breasts with the use of mammography (MMG), ultrasound (US), and
      magnetic resonance imaging (MRI) before surgery. After PM, the specimens were
      divided about 1 cm serially and examined in their entirety. RESULTS: Of 1527
      registrees who underwent BRCA testing, 1125 (73.7%) were negative for BRCA1/2
      mutation, 297 (19.5%) were positive for BRCA1/2 mutation (BRCA1/2MUT+), and 105
      (6.9%) had uncertain results. To decide whether to undergo total mastectomy vs.
      breast-conserving surgery (BCS), 370 registrees underwent presurgical genetic
      testing. During the follow-up period, four new-onset breast cancers were found
      among the 55 non-affected BRCA carriers. Among the 73 BRCA1/2MUT+ carriers who
      underwent BCS, 3 were found to have ipsilateral breast cancer. Of 189 BRCA1/2MUT+
      carriers with unilateral breast cancer, 8 were found to have contralateral breast
      cancer. Of 53 PM specimens, 6 (11.3%) were found to have occult breast cancer
      despite using MMG, US, and MRI. CONCLUSIONS: Our report showed a relatively
      higher incidence rate of occult cancer at 11.3% in PM specimens despite thorough
      pre-operative radiological evaluations, which included a breast MRI. Considering
      the occult cancer rates and the various pathological methods of our study and
      published studies, we propose the necessity of a histopathological protocol.

PMID- 30203343
TI  - Amino-Fe3O4-functionalized graphene oxide as a novel adsorbent of Methylene Blue:
      kinetics, equilibrium, and recyclability aspects.
AB  - Graphene oxide (GO) was synthetized from graphite oxidation via the modified
      Hummers method. Afterwards, the GO was functionalized with diethylenetriamine
      (DETA) and FeCl3 to obtain the novel amino-iron oxide functionalized graphene (GO
      NH2-Fe3O4). FTIR, XRD, SEM with EDX, and Raman spectroscopy were performed to
      characterize both GO and GO-NH2-Fe3O4. The GO-NH2-Fe3O4 was then evaluated as
      adsorbent of the cationic dye Methylene Blue (MB); analysis of the point of zero
      net charge (pHPZC) and pH effect showed that the GO-NH2-Fe3O4 pHPZC was 8.2;
      hence, the MB adsorption was higher at pH 12.0. Adsorption kinetics studies
      indicated that the system reached the equilibrium state after 5 min, with
      adsorption capacity at equilibrium (qe) and kinetic constant (kS) of 966.39 mg g
      1 and 3.17?10-2 g mg-1 min-1, respectively; moreover, the pseudo-second-order
      model was better fitted to the experimental data. Equilibrium studies showed
      maximum adsorption capacity of 1047.81 mg g-1; furthermore, Langmuir isotherm
      better fitted the adsorption. Recycling experiments showed that the GO-NH2-Fe3O4
      maintained the MB removal rate above 95% after 10 cycles. All the results showed
      sorbent high adsorption capacity and outstanding regeneration capability and
      evidenced the employment of novel GO-NH2-Fe3O4 as a profitable adsorbent of
      textile dyes.

PMID- 30203344
TI  - The process of climate change in mass media discourse using the example of Polish
      and international editions of "Newsweek" magazine.
AB  - The main objective of the article is to conduct a critical media discourse
      analysis as presented in the Polish and international editions of the "Newsweek"
      magazine in the years 2001-2006 and 2012-2016; the subject of which was climate
      change. The introduction provides the definitions of the key terms, such as: the
      greenhouse effect and critical discourse analysis (CDA). The theoretical part
      presents the most important assumptions of the CDA and presents a characteristic
      of the weekly. The results of the conducted quantitative and qualitative analysis
      partially lead to varying conclusions. Based on the CDA, the hypothesis was
      assumed that more attention was provided to climate change in the international
      (English) edition of "Newsweek", than in the Polish-language edition. Rejected in
      turn was the hypothesis, according to which, more importance to climate change
      and their repercussions was provided in the discourse within the last 5 years of
      publication of the weekly than in the discourse from the years 2001-2006. As a
      result of comparison of both discourses, the disturbing fact that media discourse
      did not present and encourage among the readers an active stance in favour of the
      climate was noticed. It is the task of this influential weekly, the message of
      which reaches many people, not only to provide knowledge and shape specific
      values or view, but also to encourage and popularise attitudes in favour of the
      climate. If man wants to continue to live on earth, then one of their goals is to
      modify the form of discourse by entities responsible for its form.

PMID- 30203345
TI  - Potential of guava leaves for mitigating methane emissions and modulating ruminal
      fermentation characteristics and nutrient degradability.
AB  - Guava leaves (Psidium guajava, GL), a high-phenolic- and flavonoid-containing
      plant resource capable of substituting the high-quality forage, may help in
      mitigating ruminal methane (CH4) emission without adverse impact on nutrient
      degradability if supplemented at an appropriate level. In order to test this
      hypothesis, rumen fermentation, CH4 production, and nutrient degradability of GL
      either solely or as a substitute of berseem hay (Trifolium alexandrinum, BH) were
      evaluated in a diet containing 50:50 concentrate to roughage. Five different
      levels of GL (0, 12.5, 25, 37.5, and 50%) were tested in vitro after 24 h
      incubation using a semi-automated gas production (GP) system. The current
      findings indicated that merely the presence of GL resulted in significantly lower
      values for cumulative GP (P < 0.001), CH4 emission (P < 0.05), truly degraded dry
      matter (TDDM; P < 0.001), truly degraded organic matter (TDOM; P < 0.001), and
      ammonia nitrogen (NH3-N) concentration (P < 0.001); however, pH (P < 0.001) and
      partitioning factor (P < 0.001) were higher. The total and individual volatile
      fatty acid (VFA) concentrations were drastically declined with GL as compared to
      BH (P < 0.05). A negative linear correlation was recorded between the levels of
      GL and GP including CH4 production (P < 0.05). The addition of GL up to 25% did
      not pose any negative effect on both TDDM and TDOM values along with NH3-N
      concentration. In addition, the inclusion of GL up to 25% did not affect the
      total or individual VFA concentration. Conclusively, in a medium concentrate
      diet, use of 25% GL and 25% BH in animal diet could be a promising alternative
      for mitigating the CH4 production without any deleterious effect on nutrient
      degradability.

PMID- 30203346
TI  - Modelling the relationship between poverty, environment, and institutions: a
      panel data study.
AB  - The paper examines the relationship between poverty and CO2 emission. We
      contribute by using a global panel data of 146 countries over the period 1996
      2014 and by focusing on the role of institution in poverty and environmental
      degradation nexus. The main findings are that the non-linearity relationship
      between poverty and CO2 emission could prompt a further increase in the poverty
      and environmental degradation. However, an increase in the institutional quality
      leads to a reduction in poverty and more protection to the environment. The main
      policy recommendation is that all countries need to improve their institutional
      framework so that reduction of poverty and environmental degradation can occur.

PMID- 30203347
TI  - Ecological degradation of an inland river basin and an evaluation of the spatial
      and distance effect on willingness to pay for its improvement.
AB  - Improvements in the ecological attributes of inland rivers have been projected to
      provide considerable non-market benefits, and the monetary valuation of these
      attributes has steadily increased over the past several decades. The present
      study addresses the spatial heterogeneity of the public's preference for
      ecological attributes and the distance-decay effect of willingness to pay (WTP)
      to improve various attributes of the river basin. The results revealed that
      spatial heterogeneity exists among the individuals; for example, the respondents
      of Liangzhou County prefer a large improvement in the natural landscape, forest
      coverage, and eco-tourism and are willing to pay 491.89, 369.32, and 338.37 yuan
      per year, respectively, for one unit improvement in these ecological attributes.
      Similarly, the respondents of Jinchang County value and are willing to pay
      447.60, 431.81, and 318.18 yuan for one unit improvement in tourism, forest
      coverage, and natural landscape, respectively. Furthermore, the results from the
      random parameter logit model show a significant distance-decay effect of the
      household WTP for ecological attributes. For example, the respondents living
      within 5 km of the river are willing to pay more money, that is, 832.61, 365.62,
      and 353.05 yuan per year for improving the natural landscape, water quantity, and
      grass cover, respectively. As the distance from the river increases, the
      corresponding WTP decreases, meaning that the respondents (users) living near the
      Shiyang River Basin are willing to pay more for ecological attribute improvement
      than those living far away from the river.

PMID- 30203348
TI  - Selected trace elements and metals in groundwater within Permian sediments near
      Olkusz (Zn-Pb ore mining region, S Poland).
AB  - The extensive mining of Zn-Pb ores in the Olkusz region resulted in significant
      changes of both water table level and chemical composition of water in all
      aquifers in the area. This was caused by intensive dewatering of mining
      excavations and development of a thick aeration zone reaching 150 m in a central
      part of the area. That created favorable conditions for oxidation of metal
      sulfides occurring in the ore-bearing dolomites (Middle Triassic) and started the
      process of forming readily soluble hydroxysulphates which then migrated to lower
      aquifers, including the Permian. As a result of those processes, various metals
      and other elements toxic to the water environment appeared in leaks observed in
      mine galleries. Changes in concentrations of selected elements (Fe, Mn, Zn, Pb,
      Cu, Ba, Ni, Co, As, Cr, Hg, Tl, Ag, Cd, B) in mine waters over the period of the
      last nearly 50 years were described. Water samples were collected from
      exploratory boreholes, piezometers, and wells located in investigated area
      inflows and seepages occurring in shafts and drifts excavated in Permian
      conglomerates. Mean concentrations of metals (Pb, Cd, Cr, Hg, Tl) and other toxic
      elements were surprisingly low; Pb, 3.94 MUg/L; Cd, 0.2 MUg/L; Cr, up to 2.26
      MUg/L; Hg, 0.25 MUg/L; Tl, 3.59 MUg/L; and As, 6.31 MUg/L. However, the observed
      concentrations varied significantly over time, reaching respectively up to 190
      MUg Pb/L, 60 MUg Cd/L, 15.6 MUg Cr/L, 2.67 MUg Hg/L, 81.3 MUg Tl/L, and 155 MUg
      As/L.

PMID- 30203349
TI  - Roles of hydrophobic and hydrophilic fractions of dissolved organic matter in
      sorption of ketoprofen to biochars.
AB  - Hydrophobic acid (HoA) and hydrophilic neutral (HiN) are two major fractions of
      dissolved organic matter (DOM). Their role in the sorption of ketoprofen (KTP) to
      wheat straw-derived biochars pyrolyzed at 300  degrees C (WS300) and 700  degrees
      C (WS700) was investigated to further probe the mechanisms responsible. WS700 has
      much higher pore volume and specific surface area (SSA) than WS300. Loading of
      HoA and HiN resulted in surface coverage of biochars. HoA with larger molecular
      size led to more pore blockage of biochars than HiN. Higher HoA binding affinity
      also caused a stronger competition with KTP on biochars. These factors reduced
      the accessibility of sorption sites for KTP, and significantly inhibited KTP
      sorption to biochar of lower SSA (i.e., WS300) by HoA. Water solubility (Sw) of
      KTP was slightly enhanced (3%) in the presence of HoA. In contrast, the presence
      of HiN reduced (22%) Sw of KTP. The decreased Sw of KTP by HiN exerted a more
      dominant influence than its competitive and loading effects, thus led to apparent
      enhanced sorption of KTP, especially to biochar of higher SSA (i.e., WS700). The
      results demonstrated the diverse effects of HoA and HiN on KTP sorption, which is
      helpful in understanding pharmaceutical-DOM-biochar interactions and
      environmental behaviors of pharmaceuticals.

PMID- 30203350
TI  - Utilization of freshwater mussel (Lamellidens marginalis) for the isolation of
      proteins through pH shift processing: characterization of isolates.
AB  - Study was conducted to use underutilized freshwater mussel (Lamellidens
      marginalis) for the recovery of proteins using pH shift method and to study the
      functionality and characteristics of the recovered isolates. From the pH range
      tested (pH 2.0-13.0), maximum protein yields were obtained during solubilization
      at pH 2.0 and pH 13.0 (p < 0.05). During the protein recovery process, pH 13.0
      was found to have minimal effect on proteins resulting in higher protein yields
      compared to pH 2.0. Isolates obtained by both acidic and alkaline solubilization
      processes had low stability and poor gel network. Total lipid content, total
      myoglobin, and pigment contents were reduced significantly (p < 0.05) during pH
      shift processing, resulting in whiter protein isolates and protein gels. All the
      essential amino acids were present in the isolates recovered by acid and alkaline
      solubilization, indicating the complete recovery of amino acids. No microbial
      counts were observed in any of the isolates prepared using acid and alkaline
      aided processing. Acid and alkaline solubilization (pH shift) process was found
      to be promising for the recovery of proteins from underutilized freshwater mussel
      thus by reducing the supply demand gap.

PMID- 30203351
TI  - Adsorption of basic and reactive dyes from aqueous solution onto Intsia bijuga
      sawdust-based activated carbon: batch and column study.
AB  - The adsorption behavior of basic, methylene blue (MB), and reactive, remazol
      brilliant violet 5R (RBV), dyes from aqueous solution onto Intsia bijuga sawdust
      based activated carbon (IBSAC) was executed via batch and column studies. The
      produced activated carbon was characterized through Brunauer-Emmett-Teller (BET)
      surface area and pore structural analysis, proximate and ultimate, scanning
      electron microscopy (SEM), and Fourier transform infrared spectroscopy (FTIR).
      Batch studies were performed to investigate the effects of contact time, initial
      concentration, and solution pH. The equilibrium data for both MB and RBV
      adsorption better fits Langmuir model with maximum adsorption capacity of 434.78
      and 212.77 mg/g, respectively. Kinetic studies for both MB and RBV dyes showed
      that the adsorption process followed a pseudo-second-order and intraparticle
      diffusion kinetic models. For column mode, the breakthrough curves were plotted
      by varying the flow rate, bed height, and initial concentration and the
      breakthrough data were best correlated with the Yoon-Nelson model compared to
      Thomas and Adams-Bohart model. The adsorption activity of IBSAC shows good
      stability even after four consecutive cycles.

PMID- 30203352
TI  - Air pollution control and flue gas desulfurization residues from Polish copper
      smelting facility as adsorbents of Pb(II) and Cu(II) from aqueous solutions.
AB  - This study aimed at evaluation of air pollution control residues (APCR) and flue
      gas desulfurization residues (FGDR) from copper foundry in Southwestern Poland as
      adsorbents of Cu(II) and Pb(II) from simulated wastewater. Studies of the impact
      of pH and adsorbent dose, as well as sorption isotherms, and kinetic and
      thermodynamic studies were conducted in a series of batch experiments. The
      maximum adsorption capacities were equal to 42.9 mg g-1 Cu(II) and 124.4 mg g-1
      Pb(II) for APCR and 98.8 mg g-1 Cu(II) and 124.7 mg g-1 Pb(II) for FGDR, which
      was comparable to mineral adsorbents examined in other studies. Adsorption
      isotherms followed the Langmuir model, except for Pb(II) for FGDR, which followed
      Freundlich model. Sorption kinetics for both materials was properly expressed by
      pseudo-second-order equation. Mean adsorption energy parameter suggested that the
      adsorption might have occurred via physical bonding. Thermodynamic study revealed
      that adsorption was spontaneous and endothermic for Cu(II) and not spontaneous
      and exothermic for Pb(II), with lower temperature favoring the process. The
      results suggested that both materials had high affinity towards Cu(II) and Pb(II)
      ions and could be conducted industrial scale research for consideration as
      potential adsorbents from aqueous solutions.

PMID- 30203354
TI  - TUEF2016-environmental pollution: problem and solution.

PMID- 30203355
TI  - It's OK to Talk About It: Exceptions to the Ingelfinger Rule.

PMID- 30203356
TI  - Capsule Commentary on Misra-Hebert et al., Implementing Team-Based Primary Care
      Models: A Mixed-Methods Comparative Case Study in a Large, Integrated Health Care
      System.

PMID- 30203353
TI  - Lead exposure from households and school settings: influence of diet on blood
      lead levels.
AB  - Lead is known as a potent toxicant to human health, particularly for children
      while their central nervous system is developing. The aim of this study was to
      investigate the associations between blood lead levels (BLLs) and lead exposure
      in the children's diet, home, and school environments. A cross-sectional study
      was conducted with 153 children aged 1-4 years, in four day care centers (DCCs),
      where a high prevalence of lead exposure was previously found. Lead determination
      by graphite furnace atomic absorption spectrometry (GF-AAS) was performed for
      venous blood, drinking water collected in the DCCs, and the 24-h diet (n = 64).
      Environmental screenings were conducted to evaluate lead concentrations in the
      tableware, buildings, and playground items in all DCCs and children's homes (n =
      18) by using a field-portable X-ray fluorescence analyzer (FP-XRF). The BLL mean
      was 2.71 MUg dL-1. Means for 24-h lead concentrations in the diet were 1.61 and
      2.24 MUg kg-1 of body weight (BW) in two DCCs. Lead concentrations in the water
      supply were lower than 2 MUg L-1. More than 11% of the DCCs' environmental
      analyses presented lead concentrations higher than or equal to 1 mg cm-2, as
      defined by the USEPA. The diet was not found to be a risk factor for lead
      exposure, but households and DCC settings raised concern. Children's exposure to
      lead in DCC environments, where they spend the most part of their weekdays,
      appeared to be relevant. Graphical abstract ?.

PMID- 30203357
TI  - Capsule Commentary on He et al., How Do Women View Risk-Based Mammography
      Screening? A Qualitative Study.

PMID- 30203358
TI  - The plant-growth-promoting actinobacteria of the genus Nocardia induces root
      nodule formation in Casuarina glauca.
AB  - Actinorhizal plants form a symbiotic association with the nitrogen-fixing
      actinobacteria Frankia. These plants have important economic and ecological
      benefits including land reclamation, soil stabilization, and reforestation.
      Recently, many non-Frankia actinobacteria have been isolated from actinorhizal
      root nodules suggesting that they might contribute to nodulation. Two Nocardia
      strains, BMG51109 and BMG111209, were isolated from Casuarina glauca nodules, and
      they induced root nodule-like structures in original host plant promoting
      seedling growth. The formed root nodule-like structures lacked a nodular root at
      the apex, were not capable of reducing nitrogen and had their cortical cells
      occupied with rod-shaped Nocardiae cells. Both Nocardia strains induced root hair
      deformation on the host plant. BMG111209 strain induced the expression of the
      ProCgNin:Gus gene, a plant gene involved in the early steps of the infection
      process and nodulation development. Nocardia strain BMG51109 produced three types
      of auxins (Indole-3-acetic acid [IAA], Indole-3-Byturic Acid [IBA] and Phenyl
      Acetic Acid [PAA]), while Nocardia BMG111209 only produced IAA. Analysis of the
      Nocardia genomes identified several important predicted biosynthetic gene
      clusters for plant phytohormones, secondary metabolites, and novel natural
      products. Co-infection studies showed that Nocardia strain BMG51109 plays a role
      as a "helper bacteria" promoting an earlier onset of nodulation. This study
      raises many questions on the ecological significance and functionality of
      Nocardia bacteria in actinorhizal symbioses.

PMID- 30203359
TI  - Sensory preferences of supplemented food products among cancer patients: a
      systematic review.
AB  - PURPOSE: Oral nutritional supplements and fortified foods, here considered
      supplemented food products (SFP), are recommended as part of nutrition therapy
      guidelines to treat malnutrition among cancer patients. However, their successful
      use is limited by patients' failure to meet recommended intakes. This systematic
      review aimed to identify sensory preferences for SFP among cancer patients and
      evaluate the methodologies employed in sensory preference assessment. METHODS: A
      systematic search was conducted in several relevant databases yielding 1056
      papers of which 19 met the inclusion criteria. Two authors independently selected
      papers and extracted findings. The included papers were categorized according to
      the focus of the preference assessment. RESULTS: Studies comparing sensory
      preferences for SFP of cancer patients with those of a control group suggested
      that the liking for SFP by cancer patients differs from healthy participants.
      Patient heterogeneity in site and stage of tumor, variation in study
      methodologies, and type of treatment complicated a conclusion regarding the
      effects of cancer treatment and taste changes on taste preferences. However, some
      general results were observed among the studies, such as the preference for fresh
      milk-based supplements when compared with other supplement types. CONCLUSION:
      This review highlighted the need for consistent reporting and control of
      variables that influence the sensory characteristics of SFP when sensory
      preferences are assessed in the clinical setting. Attention to these
      methodological details will enhance the reliability and accuracy of sensory
      preference assessment among cancer patients for realistic evaluation of SFP
      targeted to their nutritional needs.

PMID- 30203360
TI  - Oral and dental alterations and growth disruption following chemotherapy in long
      term survivors of childhood malignancies.
AB  - PURPOSE: More attention has been focused on the long-term side effects of
      treatment protocols since impressive advances in childhood cancer treatment have
      resulted in a growing population of patients. The purpose of this study was to
      investigate the disturbances of dento-facial development in children who were
      long-term survivors of childhood malignancies. METHODS: Fifty-three children
      (mean age, 10 years + 4 months) in long-term remission underwent oral/dental and
      radiographic examinations after completion of therapy. Crown and root
      malformations, gingival/periodontal status, enamel defects, discolorations,
      decayed and unerupted teeth, premature apexifications, agenesis, maximal
      interincisal opening and lateral movement of jaws, and soft tissue abnormalities
      were noted. Caries were evaluated by the decayed-missing-filled teeth (DMFT)
      index. Forty healthy children (mean age, 12 years + 4 months) belonging to the
      same age group and socioeconomic community were served as controls. All
      participants in the study were evaluated in terms of craniofacial development.
      RESULTS: The data of the study showed that higher prevalence of root
      malformation, unerupted teeth, and enamel hypoplasia were detected as a
      consequence of childhood cancer and/or antineoplastic therapy. Although no
      differences of craniofacial growth and development were observed between groups
      (P > 0.05), plaque and gingival index scores were statistically higher in the
      study group (P < 0.05). CONCLUSION: A range of variations in dental structures is
      recognized as a side effect of childhood cancer therapy in long-term survivors of
      pediatric malignancies that may affect their quality of life.

PMID- 30203361
TI  - Phylogenetic analysis of two genotype 3 Hepatitis E viruses from wild boar,
      Italy.
AB  - The complete and near-complete genome sequences (7206 nt and 7229 nt) of two wild
      boar HEV strains detected in Southern Italy were obtained by the next generation
      sequencing. Phylogenetic analysis and p distance comparisons of one of the
      strains with HEV-3 reference subtype strains confirmed the detection of a subtype
      3i (p distance = 0.110) strain in wild boar, never detected in Italy either in
      wild boar or pigs. The sequence of the second strain was not classifiable in any
      of the subtypes defined to date, showing a p distance > 0.138 and a low
      nucleotide identity with all HEV reference strains. The virus may represent a
      novel subtype, with a low relationship to other strains of genotype 3 detected in
      wild boar, pigs, or humans in Europe. This result suggests the circulation in
      Italy of an emerging or uncommon HEV strain. Sequencing followed by phylogenetic
      analyses of the complete HEV coding regions are important tools for understanding
      the evolutionary and epidemiological dynamics underlying the wide genetic
      diversity of HEV strains.

PMID- 30203362
TI  - Cerebellar glioblastoma: a clinical series with contemporary molecular analysis.
AB  - BACKGROUND: Glioblastomas (GBM) are localized in only less than 1% of patients in
      the cerebellum. Therefore, tumor characteristics, survival, and the efficacy of
      therapies are not yet well defined. The present study aims to characterize the
      molecular features of cerebellar GBM (GBMc) in 8 patients treated with
      contemporary modality in our institution. METHODS: Patients' treatment history,
      progression-free survival (PFS), and overall survival (OS) were analyzed. All
      histopathological specimens were re-investigated. EGFR amplification was
      determined by FISH, H3F3A, and HIST1H3B mutation status and MGMT promoter
      methylation after bisulfite treatment by pyrosequencing and BRAF V600E by
      pyrosequencing and immunohistochemistry. TERT promoter mutations were analyzed by
      Sanger sequencing, CDKN2A/B deletions by digital PCR. The expression of IDH1
      R132H, ATRX, and p53 was determined through immunohistochemistry. RESULTS: Six
      adults and two children (mean age 36 years) underwent tumor resection via medial
      or lateral suboccipital craniotomy. The median overall survival (mOS) of the
      adult patients was 7 months. GBMc from two children demonstrated a H3F3A K27M
      mutation. One of these also harbored a BRAF V600E mutation and has already had a
      PFS of 74 months. Mutated IDH1 R132H protein was expressed in 2 GBM from adult
      patients with previous supratentorial anaplastic astrocytoma. One patient carried
      a TERT promoter mutation. Another patient initially presented with a thalamic
      pilocytic astrocytoma. The cerebellar tumor revealed neither a BRAF V600E nor a
      H3F3A mutation but a homozygous CDKN2A/B deletion. CONCLUSIONS: GBM located in
      the cerebellum can be found in all age groups. We provide novel molecular genetic
      data on these rare tumors. Mutated IDH1 R132H protein and H3F3A K27M mutations
      indicate that a substantial number of GBMc are "metastatic" or "diaschismatic"
      lesions. Mutation of BRAF V600E may have a stronger biological significance than
      H3F3A K27M alterations. In a subset of patients, GBM may arise primarily as a
      distinct entity in the cerebellum.

PMID- 30203363
TI  - Use of MRI in diabetic lumbosacral radiculoplexus neuropathy: case report and
      review of the literature.
AB  - Diabetic lumbosacral radiculoplexus neuropathy is often confused with
      radiculopathy in the context of spinal degenerative disc disease including spinal
      stenosis. Accuracy in diagnosis may prevent unnecessary interventional procedures
      including selective nerve root blocks or epidural steroid injections or even
      surgery in selected cases. Our patient with known diabetes and lumbar disc
      disease presented with acute onset of pain in L5-S1 distribution of the left
      lower extremity. Initial MR imaging of the lumbar spine did not show sufficient
      structural changes to explain her symptomatology. An MR neurogram of the
      lumbosacral plexus revealed inflammation within the bilateral sciatic and femoral
      nerves; subsequent EMG demonstrated a generalized sensorimotor neuropathy but no
      evidence of plexopathy. To our knowledge, this is the first case report that
      utilized MR imaging of the pelvis to assist in the diagnosis of diabetic
      lumbosacral radiculoplexus neuropathy (DLRPN).

PMID- 30203364
TI  - Movement of giant lipid vesicles induced by millimeter wave radiation change when
      they contain magnetic nanoparticles.
AB  - Superparamagnetic iron oxide nanoparticles are used in a rapidly expanding number
      of research and practical applications in biotechnology and biomedicine. Recent
      developments in iron oxide nanoparticle design and understanding of nanoparticle
      membrane interactions have led to applications in magnetically triggered,
      liposome delivery vehicles with controlled structure. Here we study the effect of
      external physical stimuli-such as millimeter wave radiation-on the induced
      movement of giant lipid vesicles in suspension containing or not containing iron
      oxide maghemite (gamma-Fe2O3) nanoparticles (MNPs). To increase our understanding
      of this phenomenon, we used a new microscope image-based analysis to reveal
      millimeter wave (MMW)-induced effects on the movement of the vesicles. We found
      that in the lipid vesicles not containing MNPs, an exposure to MMW induced
      collective reorientation of vesicle motion occurring at the onset of MMW switch
      "on." Instead, no marked changes in the movements of lipid vesicles containing
      MNPs were observed at the onset of first MMW switch on, but, importantly, by
      examining the course followed; once the vesicles are already irradiated, a
      directional motion of vesicles was induced. The latter vesicles were
      characterized by a planar motion, absence of gravitational effects, and having
      trajectories spanning a range of deflection angles narrower than vesicles not
      containing MNPs. An explanation for this observed delayed response could be
      attributed to the possible interaction of MNPs with components of lipid membrane
      that, influencing, e.g., phospholipids density and membrane stiffening,
      ultimately leads to change vesicle movement.

PMID- 30203365
TI  - Maintaining homeostasis by controlled alternatives for energy distribution in
      plant cells under changing conditions of supply and demand.
AB  - Plants depend on light energy for the generation of ATP and reductant as well as
      on supply of nutrients (inorganic C, N, and S compounds) to successfully produce
      biomass. Any excess of reducing power or lack of electron acceptors can lead to
      the formation of reactive oxygen species (ROS). Multiple systems are operating to
      avoid imbalances and subsequent oxidative stress by efficiently scavenging any
      formed ROS. Plants can sense an upcoming imbalance and correspondingly adapt to
      changed conditions not only by an increase of ROS scavengers, but also by using
      excess incoming light energy productively for assimilatory processes in actively
      metabolizing cells of growing leaves. CO2 assimilation in chloroplasts is
      controlled by various redox-regulated enzymes; their activation state is strictly
      linked to metabolism due to the effects of small molecules on their actual
      activation state. Shuttle systems for indirect transfer of reducing equivalents
      and ATP specifically distribute the energy fluxes between compartments for
      optimal biomass production. Integration of metabolic and redox signals involves
      the cytosolic enzyme glyceraldehyde-3-P dehydrogenase (GapC) and some of its many
      moonlighting functions. Its redox- and metabolite-dependent interactions with the
      mitochondrial outer membrane, the cytoskeleton, and its occurrence in the nucleus
      are examples of these additional functions. Induction of the genes required to
      achieve an optimal response suitable for the respective conditions allows for
      growth when plants are exposed to different light intensities and nutrient
      conditions with varying rates of energy input and different assimilatory pathways
      for its consumption are the required in the long term. A plant-specific
      respiratory pathway, the alternative oxidase (AOX), functions as a site to
      convert excess electrons into heat. For acclimation, any imbalance is sensed and
      elicits signal transduction to induce the required genes. Examples for regulated
      steps in this sequence of events are given in this review. Continuous adjustment
      under natural conditions allows for adaptive responses. In contrast, sudden light
      stress, as employed when analyzing stress responses in lab experiments,
      frequently results in cell destruction. Knowledge of all the flexible regulatory
      mechanisms, their responsiveness, and their interdependencies is needed when
      plant growth is to be engineered to optimize biomass and production of any
      desired molecules.

PMID- 30203367
TI  - Association of glutathione S-transferase M1 and T1 null/present polymorphism with
      physical performance in the Korean population.
AB  - Human physical performance is a highly complex phenotype that is influenced by
      various factors. In particular, genetic factors related to muscle fiber type,
      bone density, muscle performance, and metabolic processes are known to contribute
      in varying degrees to athlete status and physical performance in various ethnic
      groups. To investigate the relationship between these genetic factors and
      physical performances, we genotyped five genetic polymorphisms (ACE Ins/Del,
      ACTN3 R577X, ER-alpha C/T, GSTM1 null/present, and GSTT1 null/present) in 111
      Korean athletes and 145 controls. We examined genotype and allele frequency
      differences between athletes and control groups, along with the odds ratios,
      using Chi square. One-way analysis of variance (ANOVA) was used to test the
      significance of differences in continuous variables between the multiple genetic
      polymorphisms and physical performance test results. The GSTM1 polymorphism
      exhibited a highly significant association in athletes (p = 0.017). Combined
      analysis of GSTM1 and GSTT1 also revealed significant differences between
      athletes and controls (p < 0.05). In the analysis of physical performance within
      athletes, the ER-alpha gene polymorphism was associated with the sargent jump and
      the side-step (p < 0.05), and the GSTM1 gene polymorphism was significantly
      associated with the 20 m shuttle run and sit-up (p < 0.05). Thus, our data imply
      that GSTM1 and ER-alpha gene polymorphisms were associated with physical
      performance in Korean athletes, although functional studies with larger sample
      sizes are necessary to elaborate upon these findings.

PMID- 30203366
TI  - Association study of the three functional polymorphisms (TAS2R46G>A, OR4C16G>A,
      and OR4X1A>T) with recurrent pregnancy loss.
AB  - This study was purposed to investigate whether genetic polymorphisms in the
      function of stop-gain are associated with a fetal or placental development play
      roles and a development of idiopathic recurrent pregnancy loss (RPL) in Korean
      females. Three stop-gain polymorphisms were selected using next-generation
      sequencing screening, which allows for the rigorous examination and discovery of
      previously uncharacterized stop-gain genes and stop-gain expression profiles.
      Accordingly, we investigated the association of stop-gain polymorphisms in Korean
      women with RPL. Three functional polymorphisms in the TAS2R46G>A (rs2708381),
      OR4C16G>A (rs1459101), and OR4X1A>T (rs10838851) genes were genotyped using
      polymerase chain reaction (PCR)-restriction fragment length polymorphism assays
      and real-time PCR analysis. We determined that the OR4C16G>A polymorphism was
      associated with idiopathic RPL in Korean women (Adjusted odds ratio [AOR] 1.782;
      95% confidence interval [CI] 1.004-3.163; P = 0.048, and AOR 1.766; 95% CI 1.020
      3.059; P = 0.042). In addition, the prevalence of RPL was increased in women with
      the OR4C16GA + AA genotype and blood coagulation measures of prothrombin time
      (PT) > 10.4 s (AOR 8.292; 95% CI 2.744-25.054). We suggest that the OR4C16G>A
      polymorphism might serve as a clinically useful biomarker for the development,
      prevention, and prognosis of RPL.

PMID- 30203368
TI  - Management of Overactive Bladder in Older Women.
AB  - PURPOSE OF REVIEW: This review will highlight our current understanding of age
      related changes in bladder function and propose important clinical considerations
      in the management of overactive bladder (OAB) specific to older women. RECENT
      FINDINGS: Frailty, functional and cognitive impairment, multimorbidity,
      polypharmacy, estrogen deficiency, and remaining life expectancy are important
      clinical factors to consider and may impact OAB symptom management in older
      women. Third-line therapies, particularly PTNS, may be preferable over second
      line therapy in some cases. Due to the complexity within this population, the
      standard treatment algorithms may not be applicable, thus a broader, more
      holistic focus is recommended when managing OAB in older women.

PMID- 30203370
TI  - Post-stroke DHA Treatment Protects Against Acute Ischemic Brain Injury by Skewing
      Macrophage Polarity Toward the M2 Phenotype.
AB  - Systemic docosahexaenoic acid (DHA) has been explored as a clinically feasible
      protectant in stroke models. However, the mechanism for DHA-afforded
      neuroprotection remains elusive. Transient middle cerebral artery occlusion
      (tMCAO) was induced for 1 h. DHA (i.p., 10 mg/kg) was administered immediately
      after reperfusion and repeated daily for 3 days. Stroke outcomes, systemic
      inflammatory status, and microglia/macrophage phenotypic alterations were
      assessed 3 days after stroke. Macrophage depletion was induced by clodronate
      liposomes injection. Primary macrophage cultures were used to evaluate the direct
      effect of DHA on macrophages. We demonstrated that post-stroke DHA injection
      efficiently reduced brain infarct and ameliorated neurological deficits 3 days
      after tMCAO. Systemic DHA treatment significantly inhibited immune cell
      infiltration (macrophages, neutrophils, T lymphocytes, and B lymphocytes) and
      promoted macrophage polarization toward an anti-inflammatory M2 phenotype in the
      ischemic brain. Meanwhile, systemic DHA administration inhibited the otherwise
      elevated pro-inflammatory factors in blood and shifted circulating macrophage
      polarity toward M2 phenotype after ischemic stroke. The numbers of circulating
      immune cells in blood and spleen, however, were equivalent between DHA- and
      vehicle-treated groups. The protective effects of DHA were macrophage-dependent,
      as macrophage depletion abolished DHA-afforded neuroprotection. In vitro studies
      confirmed that DHA suppressed production of chemokines and pro-inflammatory
      cytokines from macrophages under inflammatory stimulation. These data indicate
      that post-stroke DHA treatment ameliorated acute ischemic brain injury in a
      macrophage-dependent manner and DHA enhanced macrophage phenotypic shift toward
      an anti-inflammatory phenotype to reduced central and peripheral inflammation
      after stroke.

PMID- 30203373
TI  - SSI, SSO, SSE, SSOPI: the elusive language of complications in hernia surgery.

PMID- 30203372
TI  - Conversion surgery for an initially unresectable, locally advanced pancreatic
      cancer after induction chemotherapy and carbon-ion radiotherapy: a case report.
AB  - BACKGROUND: Pancreatic cancer has a very high mortality rate worldwide, and about
      30-40% of all patients have extensive vascular involvement at initial diagnosis
      that precludes surgical intervention. Here, we describe our experience in a
      patient with locally advanced pancreatic cancer (LAPC) who underwent R0
      conversion surgery after undergoing a combination of chemotherapy and carbon-ion
      radiotherapy (CIRT), which led to long-term relapse-free survival (23 months).
      CASE PRESENTATION: A 41-year-old woman presented a month ago with epigastralgia
      referred to our facility and was subsequently diagnosed with pancreatic cancer
      cStage III (Ph, TS2 (35 mm), cT4, cCH1, cDU1, cS1, cRP1, cPL1, cVsm0, cAsm1, cN0,
      cM0) that was also categorized as an unresectable LAPC. She immediately underwent
      3 cycles of induction chemotherapy (gemcitabine + nanoparticle albumin-bound (nab
      ) paclitaxel) followed by CIRT with concurrent gemcitabine. Although significant
      shrinkage of the primary tumor occurred, frequent cholangitis due to duodenal
      stenosis of unknown etiology prevented continued chemotherapy, and 9 months after
      the first visit, she underwent a radical, subtotal, stomach-preserving,
      pancreaticoduodenectomy (SSPPD). Histopathologic examination of the resected
      tissue revealed a R0 resection with a histological response of Evans grade IIB.
      She was administered an almost full dose of S-1 as adjuvant chemotherapy for 6
      months and has shown no signs of recurrence in 23 months. CONCLUSIONS: We report
      a first case of successful conversion surgery for an initially unresectable LAPC
      after rapid induction GEM + nab-PTX chemotherapy followed by CIRT. Rapid
      induction GEM + nab-PTX chemotherapy followed by CIRT for LAPC might be a safe
      and effective treatment option.

PMID- 30203371
TI  - Leptin gene polymorphism affects leptin level in childhood asthma.
AB  - BACKGROUND: Leptin may induce inflammation in asthma by activation of Th2 cells.
      It has also been demonstrated that leptin expression increases upon inflammation
      and that asthmatic patients show increased serum leptin levels. We hypothesized
      that the polymorphism in leptin (LEP) and leptin receptor (LEPR) genes is
      associated with childhood asthma and may affect their serum level. To our
      knowledge, there are no reports analyzing LEP and LEPR polymorphisms in
      association with their serum levels in childhood asthma. METHODS: We analyzed 35
      subjects: 25 asthmatic pediatric patients and 10 healthy children aged from 6 to
      18. The diagnosis of allergic asthma was based on clinical manifestation, lung
      function, positive skin prick tests and increased immunoglobulin E levels. The
      polymorphisms were genotyped with use of polymerase chain reaction-restriction
      fragment length polymorphism method. Serum levels of leptin and leptin receptor
      were determined using BioVendor enzyme-linked immunosorbent assay kits.
      Statistical analysis was done with Statistica v.12. RESULTS: We observed that
      leptin levels were increased in asthmatic subjects as compared to healthy
      controls and were significantly higher during exacerbation than in the
      asymptomatic period (P = 0.025). We observed that LEP polymorphism (rs13228377)
      was associated with higher serum leptin levels in asthma and these two variables
      had high predictive value for asthma risk (P = 0.007, odds ratio 17.5, predictive
      accuracy 83.9%). LEPR polymorphisms did not show association with its serum level
      and asthma risk. CONCLUSION: LEP polymorphism may increase asthma risk via
      influence on its serum level.

PMID- 30203374
TI  - Cinacalcet as rescue therapy for refractory hyperparathyroidism in young children
      with advanced chronic kidney disease.
AB  - BACKGROUND: Studies in the use of the calcimimetic, cinacalcet, in pediatric
      chronic kidney disease (CKD) are few and limited to older children with secondary
      hyperparathyroidism (sHPT), a major morbid complication contributing to poor
      growth, bone deformities, and cardiovascular disease. Our objectives were to
      determine a safe and effective dosing regimen of cinacalcet in the treatment of
      infants and young children with sHPT that was refractory to standard care and to
      examine their growth during treatment. METHODS: Ten young pediatric patients with
      advanced CKD were studied retrospectively during 11 courses of treatment with
      cinacalcet. All had severe sHPT with intact parathyroid hormone (iPTH) levels >=
      500 pg/ml and were refractory to standard therapy with phosphate binders and
      active vitamin D analogs at high doses for > 30 days. The cinacalcet dose was
      advanced by 50% every 2-4 weeks to achieve a decline in the iPTH to a goal of 150
      300 pg/ml. Linear growth was assessed at 6-month intervals by change in z-scores
      (?SDS) for length before and during cinacalcet therapy. RESULTS: Median age at
      initiation of cinacalcet was 18 months (IQR 6, 36) with an average starting dose
      of 0.7 +/- 0.2 mg/kg/day. Median effective dose required to reach iPTH goal of
      150-300 pg/ml was 2.8 mg/kg/day (IQR 2.0, 3.1), and time to goal was 112 days
      (IQR 56, 259) with a median overall decline in iPTH of 82% from baseline by 6
      months (p < 0.0001). No subject experienced a clinical adverse event, although 4
      had biochemical asymptomatic hypocalcemia. Linear growth improved significantly
      during cinacalcet therapy (?SDS - 0.62 +/- 1.2 versus + 0.91 +/- 1.4; p < 0.005).
      By multiple regression analysis, the primary determinants of growth were
      concurrent treatment with growth hormone and age < 2 years (R2 = 89.6%; p <
      0.001). A shorter treatment time required to achieve iPTH goals also was
      associated with improved growth (r = - 0.75; p < 0.01). CONCLUSIONS: Cinacalcet
      may be used effectively and safely in infants and small children with refractory
      sHPT in advanced CKD using a cautious dosing regimen. Cinacalcet successfully
      brings iPTH to target level and supports growth when other treatments have been
      ineffective.

PMID- 30203375
TI  - Biologics for childhood systemic vasculitis.
AB  - Recent advances have allowed better understanding of vasculitis pathogenesis and
      led to more targeted therapies. Two pivotal randomized controlled trials,
      RITUXVAS and rituximab in ANCA-associated vasculitis (RAVE), provide high-quality
      evidence demonstrating rituximab (RTX) is efficacious in inducing remission in
      adult ANCA-associated vasculitis (AAV) patients compared with cyclophosphamide
      (CYC). RAVE also demonstrated superiority of RTX to oral CYC for induction of
      remission in relapsing disease. Disappointingly, the RTX regimen was not
      associated with reduction in early serious adverse events. At least nine
      randomized trials are in progress, aiming to further delineate optimal dosing and
      duration of RTX therapy in AAV. In particular, the 6-month interim results of the
      PEPRS trial provide encouraging data specific to children. Due to special
      concerns related to growth, preservation of fertility, and potential for high
      cumulative medication doses, children with AAV should be considered as candidates
      for RTX even as a first-line remission induction therapy. Two randomized clinical
      trials have defined the role of infliximab in Kawasaki disease (KD), which
      appears to be as an alternative to a second infusion of intravenous
      immunoglobulin (IVIG) for treatment-resistant disease. Support for other
      biologics in the treatment of AAV or for biologics in the treatment of other
      vasculidities is largely lacking due to either unimpressive trial results or lack
      of trials. Except for the KD trials and the PEPRS, trials enrolling children
      remain scant. This review touches on the key trials and case series with
      biologics in the treatment of vasculitis that have influenced practice and shaped
      current thinking.

PMID- 30203377
TI  - Exploring the 'Patient Experience' of Individuals with Limited English
      Proficiency: A Scoping Review.
AB  - Individuals with limited English proficiency (LEP) face barriers to safe and high
      quality health care. 'Patient-experience' is increasingly viewed as an important
      component of health care quality. However, the impact of language proficiency on
      'patient-experience' is not well-described. This scoping review mapped the
      literature on the patient experience of individuals with LEP. We reviewed sixty
      qualitative and mixed-methods studies from EMBASE and MEDLINE published between
      2007 and 2017. We identified four major themes: (1) Communication, language
      barriers, and health literacy, (2) Relationships with health care professionals,
      (3) Discrimination and intersection with other dimensions of identity, and (4)
      Cultural safety. We also identified factors that may improve LEP patient
      experience, including: mitigating language barriers through interpretation or
      language-concordant providers, offering translated patient resources, and
      educating health care professionals about cultural safety.

PMID- 30203376
TI  - Periprosthetic Joint Infection in Patients with Inflammatory Joint Disease:
      Prevention and Diagnosis.
AB  - PURPOSE OF REVIEW: Periprosthetic joint infection (PJI) is a devastating
      complication that can occur following total joint arthroplasty (TJA), causing
      significant morbidity and often requiring revision surgery. This goal of this
      manuscript is to review the current evidence for the prevention and diagnosis of
      PJI in patients with inflammatory arthritis. RECENT FINDINGS: Patients with
      inflammatory arthritis have a higher risk of PJI after TJA; however, there are
      several preventive, diagnostic, and therapeutic measures that can be optimized to
      lower the burden of PJI in this population. This manuscript will review the
      current evidence and clinical practice recommendations that support specific
      features of preoperative evaluation, perioperative medication management, and
      surgical planning in inflammatory arthritis patients undergoing TJA. Evidence and
      recommendations for the diagnosis of PJI in this patient population will also be
      reviewed. Despite increased research efforts directed towards PJI, specific
      approaches directed at the inflammatory arthritis patient population remain
      surprisingly limited. Optimization strategies such as adequately managing disease
      modifying medications, treating preoperative anemia, encouraging smoking
      cessation, and improving weight management are strongly encouraged before
      entering the perioperative period. If PJI does occur in the inflammatory
      arthritis patient, establishing the diagnosis is challenging, since guidelines
      were created from investigations of PJI in primarily patients without
      inflammatory arthritis. Future prospective research is required to better guide
      clinicians in preventing and diagnosing PJI in inflammatory arthritis patients
      undergoing TJA.

PMID- 30203378
TI  - Changes in biophysical characteristics of PFN1 due to mutation causing
      amyotrophic lateral sclerosis.
AB  - Single amino acid mutations in profilin 1 (PFN1) have been found to cause
      amyotrophic lateral sclerosis (ALS). Recently, we developed a mouse model for ALS
      using a PFN1 mutation (glycine 118 to valine, G118V), and we are now interested
      in understanding how PFN1 becomes toxically lethal with only one amino acid
      substitution. Therefore, we studied mutation-related changes in the PFN1 protein
      and hypothesized that such changes significantly disturb its structure.
      Initially, we expressed and studied the purified PFN1WT and PFN1G118V proteins
      from bacterial culture. We found that the PFN1G118V protein has a different mean
      residue ellipticity, as measured by far-UV circular dichroism, accompanied by a
      spectral shift. The intrinsic fluorescence of PFN1G118V showed a small
      fluctuation in maximum fluorescence absorption and intensity. Moreover, we
      examined the time course of PFN1 aggregation using SDS-PAGE, western blotting,
      and MALDI-TOF/TOF and found that compared with PFN1WT, PFN1G118V had an increased
      tendency to form aggregates. Dynamic light scattering data confirmed this,
      showing a larger size distribution for PFN1G118V. Our data explain why PFN1G118V
      tends to aggregate, a phenotype that may be the basis for its neurotoxicity.

PMID- 30203379
TI  - Gene Delivery to Tobacco Root Cells with Single-Walled Carbon Nanotubes and Cell
      Penetrating Fusogenic Peptides.
AB  - Development of efficient, easy, and safe gene delivery methods is of great
      interest in the field of plant biotechnology. Considering the limitations of the
      usual transfection methods (such as transgene size and plant type), several new
      techniques have been tested for replacement. The success of some biological and
      synthetic nanostructures such as cell-penetrating peptides and carbon nanotubes
      in transferring macromolecules (proteins and nucleic acids) into mammalian cells
      provoked us to assess the ability of an engineered chimeric peptide and also
      arginine functionalized single-walled carbon nanotube in gene delivery to intact
      tobacco (Nicotiana tabacum var. Virginia) root cells. It was suggested that the
      engineered peptide with its special cationic and hydrophobic domains and the
      arginine functionalized single-walled carbon nanotube due to its nano-cylindrical
      shape can pass plant cell barriers while plasmid DNA (which codes green
      fluorescent protein) has been condensed on them. The success of gene delivery to
      tobacco root cells was confirmed by fluorescence microscopy and western blotting
      analysis.

PMID- 30203380
TI  - Heparin-binding protein in ventilator-induced lung injury.
AB  - BACKGROUND: Although mechanical ventilation is often lifesaving, it can also
      cause injury to the lungs. The lung injury is caused by not only high pressure
      and mechanical forces but also by inflammatory processes that are not fully
      understood. Heparin-binding protein (HBP), released by activated granulocytes,
      has been indicated as a possible mediator of increased vascular permeability in
      the lung injury associated with trauma and sepsis. We investigated if HBP levels
      were increased in the bronchoalveolar lavage fluid (BALF) or plasma in a pig
      model of ventilator-induced lung injury (VILI). We also investigated if HBP was
      present in BALF from healthy volunteers and in intubated patients in the
      intensive care unit (ICU). METHODS: Anaesthetized pigs were randomized to receive
      ventilation with either tidal volumes of 8 ml/kg (controls, n = 6) or 20 ml/kg
      (VILI group, n = 6). Plasma and BALF samples were taken at 0, 1, 2, 4, and 6 h.
      In humans, HBP levels in BALF were sampled from 16 healthy volunteers and from 10
      intubated patients being cared for in the ICU. RESULTS: Plasma levels of HBP did
      not differ between pigs in the control and VILI groups. The median HBP levels in
      BALF were higher in the VILI group after 6 h of ventilation compared to those in
      the controls (1144 ng/ml (IQR 359-1636 ng/ml) versus 89 ng/ml (IQR 33-191 ng/ml)
      ng/ml, respectively, p = 0.02). The median HBP level in BALF from healthy
      volunteers was 0.90 ng/ml (IQR 0.79-1.01 ng/ml) as compared to 1959 ng/ml (IQR
      612-3306 ng/ml) from intubated ICU patients (p < 0.001). CONCLUSIONS: In a model
      of VILI in pigs, levels of HBP in BALF increased over time compared to controls,
      while plasma levels did not differ between the two groups. HBP in BALF was high
      in intubated ICU patients in spite of the seemingly non-harmful ventilation,
      suggesting that inflammation from other causes might increase HBP levels.

PMID- 30203381
TI  - Tolerable and curable treatment in HIV/HCV co-infected patients using anti-HCV
      direct antiviral agents: a real-world observation in China.
AB  - OBJECTIVE: No brand direct-acting antiviral agents (DAAs) are available for
      treatment of HIV-1/HCV co-infected patients in China. This study aimed to observe
      the therapeutic efficacy and safety of generic DAAs for affected Chinese
      patients. DESIGN: Real-world setting to elucidate whether DAAs were tolerated and
      effective in HIV-1/HCV co-infected patients. METHODS: 176 HIV-1/HCV co-infected
      patients received anti-HCV DAA treatment together with ART regimens for HIV
      infection. Among the 176 patients, 99 patients were treated with SOF + DCV +/-
      RBV, 60 patients were treated with SOF + LDV +/- RBV, and 17 patients received
      SOF + RBV +/- Peg-IFN regimens, for 12 or 24 weeks, respectively. The primary
      endpoint was undetectable HCV RNA 12 weeks after therapy was completed (SVR12).
      Data pertaining to safety and adverse events were analyzed. RESULTS: 151/176 HIV
      1/HCV co-infected patients finished the treatment and 12-week follow-up. SVR12
      for the patients treated with regimens of SOF + DCV, SOF + DCV+RBV, SOF + Peg
      IFN+RBV, SOF + RBV, SOF + LDV, and SOF + LDV+RBV for 12 or 24 weeks was 100%
      (75/75), 100% (11/11), 100% (14/14), 100% (2/2), 95.2% (40/42), and 100% (7/7),
      respectively. HIV-1/HCV co-infected patients with liver cirrhosis achieved well
      SRV12. Notably, there was no significant difference in adverse effects among
      patients with different baseline CD4+ T-cell count in those who received DAA
      regimens with or without Peg-IFN and RBV. CONCLUSION: We showed generic SOF + DCV
      and SOF + LDV regimens were well tolerated and with high efficiency. Patient's
      baseline CD4+ T-cell count did not exhibit significant difference in adverse
      effects.

PMID- 30203384
TI  - Electrographic Seizures in Patients with Acute Encephalitis.
AB  - INTRODUCTION: Clinical seizures and status epilepticus are frequent complications
      of encephalitis, can lead to depressed level of consciousness, and are associated
      with poor outcome. We sought to determine the frequency, risk factors, and
      clinical impact of electrographic seizures detected with continuing
      electroencephalography (cEEG) in patients with encephalitis and altered level of
      consciousness. METHODS: We retrospectively identified all patients with presumed
      or definite viral or autoimmune encephalitis who underwent cEEG monitoring at
      Henry Ford Hospital from January 2012 to October 2017. Clinical data and cEEG
      monitoring reports were abstracted and recorded. The primary outcome was
      electrographic seizures detected by cEEG. RESULTS: Of 1,735 patients who
      underwent a minimum of 12 h of cEEG monitoring, we identified 54 with a verified
      discharge diagnosis of encephalitis. Twenty-two of these patients (41%) had
      electrographic seizures on cEEG. Compared with encephalitis patients without
      seizures, electrographic seizures were associated with lower serum sodium levels
      (137 +/- 5 vs 141 +/- 7, P = 0.027) and more often were on antiepileptic therapy
      (100% vs 78%, P = 0.033) on the first day of monitoring. Seizures were also
      associated with a higher frequency of cortical imaging abnormalities (68% vs 28%,
      P = 0.005), lateralized periodic discharges (LPDs; 50% vs 16%, P = 0.014), delta
      background frequency (81% vs 45%, P = 0.010), low or suppressed voltage (96% vs
      62%, P = 0.005), and focal slowing (86% vs 47%, P = 0.004). There was no
      association between electrographic seizures and clinical outcome at discharge.
      CONCLUSION: Electrographic seizures occur in approximately 40% of patients with
      acute encephalitis. Low serum sodium, cortical imaging abnormalities, and on cEEG
      LPDs and background abnormalities are associated factors. The lack of association
      with short-term outcome suggests that with aggressive treatment, the clinical
      impact of electrographic seizures in encephalitis can be minimized.

PMID- 30203385
TI  - The Impact of Intrahospital Transports on Brain Tissue Metabolism in Patients
      with Acute Brain Injury.
AB  - BACKGROUND: Patients with severe acute brain injury (ABI) often require
      intrahospital transports (IHTs) for repeated computed tomography (CT) scans. IHTs
      are associated with serious adverse events (AE) that might pose a risk for
      secondary brain injury. The goal of this study was to assess IHT-related
      alterations of cerebral metabolism in ABI patients. METHODS: We included
      mechanically ventilated patients with ABI who had continuous multimodality
      neuromonitoring during an 8-h period before and after routine IHT. Intracranial
      pressure (ICP), cerebral perfusion pressure (CPP), brain tissue oxygenation
      (PtiO2) as well as cerebral and subcutaneous microdialysis parameters (lactate,
      pyruvate, glycerol, and glutamate) were recorded. Values were compared between an
      8-h period before (pre-IHT) and after (post-IHT) the IHT. RESULTS: A total of 23
      IHT for head CT scans in 18 patients were analyzed. Traumatic brain injury (n =
      7) was the leading cause of ABI, followed by subarachnoid hemorrhage (n = 6) and
      intracerebral hemorrhage (n = 5). The analyzed microdialysis parameters in the
      brain tissue as in the subcutaneous tissue did not show significant changes
      between the pre-IHT and post-IHT period. In addition, we observed no significant
      increase in ICP or decrease in CPP and PtiO2 in the 8-h period after IHT.
      CONCLUSIONS: While the occurrence of AE during IHT is a known risk factor for ABI
      patients, our results demonstrate that IHTs do not alter the brain tissue
      chemistry in a significant manner. This fact may help assess the risk for routine
      IHT more accurately.

PMID- 30203382
TI  - Approach and management of dysnatremias in cirrhosis.
AB  - Hypervolemic (dilutional) hyponatremia is the most common dysnatremia in
      cirrhosis, with a prevalence close to 50% in patients with ascites, while
      hypovolemic hyponatremia occurs in a minority of cases. Hyponatremia carries a
      poor prognosis, being associated with increased mortality and reduced survival
      after liver transplantation. Hypernatremia is rarer and is also associated with
      an adverse prognosis. Increased non-osmotic secretion of arginine vasopressin and
      altered renal tubular sodium handling due to impaired free water generation are
      the mechanisms leading to hypervolemic hyponatremia, while diuretic-induced fluid
      loss is the main cause of hypovolemic hyponatremia. Hypernatremia usually follows
      hypotonic fluid losses due to osmotic diuresis (glycosuria) or lactulose-induced
      diarrhea. The main clinical manifestations of dysnatremias are due to their
      effects on the central nervous system: astroglial cell hyperhydration follows
      hyponatremia-an abnormality that exacerbates ammonia neurotoxicity-while the
      opposite abnormality occurs with hypernatremia. Asymptomatic or mildly
      symptomatic hypervolemic hyponatremia is mainly managed by correcting of
      precipitating factors and non-osmotic fluid restriction. Severe, life-threatening
      hyponatremia requires hypertonic saline infusion, avoiding rapid and complete
      correction of serum sodium concentration to prevent neurological sequelae such as
      osmotic demyelination. V2 receptor blockade by vaptans may be considered in
      patients with sustained hyponatremia waitlisted for liver transplantation.
      Diuretic withdrawal and plasma volume expansion are required in hypovolemic
      hypernatremia. Prompt recognition, removal of the precipitating factor(s) and non
      osmotic fluid administration represent the mainstays of hypernatremia management.
      Rapid correction of long-standing hypernatremia can lead to cerebral edema and
      has to be avoided.

PMID- 30203383
TI  - 3-O-Methyl-D-glucose mutarotation and proton exchange rates assessed by 13C, 1H
      NMR and by chemical exchange saturation transfer and spin lock measurements.
AB  - 3-O-Methyl-D-glucose (3OMG) was recently suggested as an agent to image tumors
      using chemical exchange saturation transfer (CEST) MRI. To characterize the
      properties of 3OMG in solution, the anomeric equilibrium and the mutarotation
      rates of 3OMG were studied by 1H and 13C NMR. This information is essential in
      designing the in vivo CEST experiments. At room temperature, the ratio of alpha
      and beta 3OMG anomers at equilibrium was 1:1.4, and the time to reach 95%
      equilibrium was 6 h. The chemical exchange rates between the hydroxyl protons of
      3OMG and water, measured by CEST and spin lock at pH 6.14 and a temperature of 4 
      degrees C, were in the range of 360-670 s-1.

PMID- 30203387
TI  - Correction to: Gadobutrol: A Review in Contrast-Enhanced MRI and MRA.
AB  - The article Gadobutrol: A Review in Contrast-Enhanced MRI and M.

PMID- 30203386
TI  - Evaluation of Drug-Drug Interaction Potential between Baloxavir Marboxil and
      Oseltamivir in Healthy Subjects.
AB  - BACKGROUND AND OBJECTIVE: Baloxavir marboxil is a prodrug that is metabolized to
      baloxavir acid, which suppresses viral replication by inhibiting cap-dependent
      endonuclease with a single oral administration. As the mode of action of
      baloxavir marboxil is different from that of neuraminidase inhibitors, such as
      oseltamivir, combination treatment with these drugs can be a treatment option,
      particularly for severe influenza infection. The aim of this study was to assess
      the drug-drug interaction between baloxavir marboxil and oseltamivir. METHODS:
      Eighteen healthy adult subjects received three treatments in a crossover fashion:
      single administration of baloxavir marboxil 40 mg alone, repeated twice-daily
      administration of oseltamivir at 75 mg for 5 days, or single administration of
      baloxavir marboxil at 40 mg in combination with repeated twice-daily
      administration of oseltamivir at 75 mg for 5 days. RESULTS: The ratios (90%
      confidence intervals) of maximum plasma concentration and area under the plasma
      concentration-time curve of baloxavir acid after co-administration compared to
      baloxavir marboxil alone were 1.03 (0.92-1.15) and 1.01 (0.96-1.06),
      respectively. The ratios (90% confidence intervals) of maximum plasma
      concentration and area under the plasma concentration-time curve of oseltamivir
      carboxylate, the active form of oseltamivir, after co-administration compared to
      oseltamivir alone were 0.96 (0.93-1.00) and 0.99 (0.96-1.01), respectively, at
      steady state on day 5. Treatment-emergent adverse events reported were mild and
      not considered to be related to the study drug. CONCLUSION: The lack of a
      clinically meaningful drug-drug interaction between baloxavir marboxil and
      oseltamivir has been established.

PMID- 30203388
TI  - [Intraoral voice recording-towards a new smartphone-based method for vocal
      rehabilitation. German version].
AB  - After laryngectomy, a new voice is needed. We present the first steps in the
      development of a smartphone-based method. A microphone is placed in the mouth to
      record the pseudo-whispering voice of laryngectomized patients. This recording is
      analyzed by voice recognition software followed by voice synthesis. Eventually,
      this will be performed on a smartphone. We placed a microphone at 10 different
      places inside and outside the mouth (two in front of the mouth (at 2 and 20 cm),
      five on the palate and three on the lower jaw) and made voice recordings in eight
      healthy men. These recordings were analyzed by voice recognition software. The
      text generated by the software was compared with the original text. Over all
      positions, the correct detection of words recorded in the mouth was 19.3% vs.
      75.2% (p = 0.01) outside the mouth. In the mouth, recording taken on the maxilla
      (22.8%) was much better than on the mandible (13.5%) (p = 0.01). The optimum
      position for a microphone on the maxilla was at the highest point of the palate
      with 31.9% correct word identification there (p = 0.028). Further investigations
      have to be undertaken with forthcoming development of smartphone processing power
      and with development of a smartphone-based voice recognition application.

PMID- 30203389
TI  - Local Effects Following Single and Repeat Intra-Articular Injections of
      Triamcinolone Acetonide Extended-Release: Results from Three Nonclinical Toxicity
      Studies in Dogs.
AB  - INTRODUCTION: Single intra-articular (IA) injections of poly(lactic-co-glycolic
      acid) (PLGA) microsphere-based triamcinolone acetonide extended-release (TA-ER;
      formerly FX006) demonstrated sustained, clinically relevant benefits in patients
      with knee osteoarthritis. The local effects of TA-ER were assessed in normal
      canine knees in three nonclinical studies. METHODS: Knees were evaluated for up
      to 6 weeks or 9 months after a single injection of TA-ER (2.1/6.25/18.75 mg TA),
      or TA crystalline suspension (TAcs, 18.75 mg TA), and for up to 6 months after
      three injections (every 1 or 3 months) of TA-ER (6.25/18.75 mg TA) or TAcs (18.75
      mg). Vehicle-diluent, blank microspheres, and untreated knees were used as
      controls. Plasma and synovial fluid (SF) TA concentrations and standard
      histopathological assessment of the synovium were conducted. Articular cartilage
      morphology was assessed via modified Mankin scoring. RESULTS: Plasma and SF
      concentrations indicated prolonged dose-dependent TA joint residency with TA-ER
      compared with TAcs. Effects in articular cartilage were dose- and time-dependent
      and consistent with known effects of corticosteroids in the normal knee. Loss of
      Safranin O staining occurred, indicative of a reduction in cartilage matrix
      proteoglycan, and recovered in a similar manner for TA-ER and TAcs across all
      studies. Structural lesions were infrequent and generally comparable in severity
      between TA-ER and TAcs but slightly higher in incidence for TA-ER.
      Focal/multifocal foreign-body responses (FBR) to PLGA were observed in the
      superficial layer of the synovium, peaking after 4-6 weeks, with significant
      recovery or complete resolution by month 6. CONCLUSIONS: These findings suggest
      that the effects of IA injections of TA-ER on cartilage are predominantly
      transient, and comparable to those observed with TAcs in the normal canine knee
      joint. These mild effects in the normal joint differ from the beneficial effects
      observed with TA-ER and other corticosteroids in disease models. The synovial FBR
      to PLGA microspheres was focal and transient. FUNDING: Flexion Therapeutics, Inc.
      Plain language summary available for this article.

PMID- 30203390
TI  - [Application of motorized intramedullary lengthening nails in skeletally immature
      patients : Indications and limitations].
AB  - BACKGROUND: Limb lengthening and deformity correction with motorized
      intramedullary lengthening nails is a more comfortable and equally safe procedure
      than the use of external fixators. While this treatment is a well-established
      method in adults, intramedullary nailing for skeletally immature patients remains
      a challenge and is the focus of current clinical investigations. OBJECTIVE:
      Elucidation of the indications for the application of femoral and tibial
      lengthening nails in skeletally immature patients, presentation of essential
      characteristics and limitations of the treatment. MATERIAL AND METHODS: Treatment
      of skeletally immature patients up to 16 years old who had a lengthening nail
      inserted was retrospectively clinically and radiologically evaluated (2016-2018).
      RESULTS: A total of 60 procedures were performed on 54 patients. Mean age at the
      time of surgery was 13.6 years and the mean follow-up time was 10 months.
      Different nailing approaches were used: antegrade femoral (n = 42), retrograde
      femoral (n = 10) and antegrade tibial (n = 8). The average amount of lengthening
      was 45 mm. In 58 of the 60 cases (96.7%) the desired amount of lengthening was
      achieved, while 2 patients experienced complications that required interruption
      of the treatment. None of the patients developed growth disorders associated with
      the nailing approach. CONCLUSION: Different approaches for intramedullary
      lengthening nails can be used in children and adolescents to correct leg length
      discrepancy with or without concomitant deformities. The treatment is limited by
      the size of the available nails, the residual growth and extent of the deformity.
      Larger trials will be needed to further validate the application of lengthening
      nails in skeletally immature patients.

PMID- 30203391
TI  - Comparison of effects of aldosterone receptor antagonists spironolactone and
      eplerenone on cardiovascular outcomes and safety in patients with acute
      decompensated heart failure.
AB  - Differences in the clinical impacts of the aldosterone receptor antagonists
      spironolactone and eplerenone in patients with heart failure (HF) are unclear.
      Among 838 prospectively enrolled patients hospitalized for HF, 90 treated with
      eplerenone were compared with 90 treated with spironolactone. The primary
      endpoint was a composite of cardiovascular death and hospitalization. A serial
      evaluation of the clinical parameters was performed 1 year after discharge. The
      mean dose of spironolactone was 27 +/- 8 mg and of eplerenone was 34 +/- 15 mg.
      During follow-up (mean 594 +/- 317 days), primary endpoints occurred in 27
      patients in the eplerenone group (30.0%) and 25 patients in the spironolactone
      group (27.8%). There were no significant intergroup differences in the primary
      endpoint (log-rank, p = 0.956). Serial changes in left ventricular ejection
      fraction, serum brain natriuretic peptide, systolic blood pressure, and estimated
      glomerular filtration rate did not differ significantly between groups. Although
      gynecomastia in men was common in the spironolactone group (p = 0.018), the
      discontinuation rates due to adverse events were similar in the two groups (p =
      0.135). Subgroup analyses suggested that eplerenone was associated with a lower
      hazard rate of the primary endpoint in female patients (interaction, p = 0.076).
      Among patients with HF, eplerenone and spironolactone have similar impacts on
      cardiovascular outcomes and safety.

PMID- 30203392
TI  - Onyx embolization of a ruptured anterior inferior cerebellar artery in a neonate.
AB  - Aneurysmal subarachnoid hemorrhage (SAH) is rare in neonates. The authors present
      a unique report of a neonate with SAH from anterior inferior cerebellar artery
      (AICA) aneurysm rupture that was successfully treated with Onyx embolization.
      This case report demonstrates the utility of Onyx embolization for posterior
      circulation aneurysms in neonates and the successful management of SAH in this
      population.

PMID- 30203393
TI  - Simplified plasma essential amino acid-based profiling provides metabolic
      information and prognostic value additive to traditional risk factors in heart
      failure.
AB  - In heart failure (HF), metabolic disturbances represent functional perturbations
      in peripheral tissues and also predict patient outcomes. This study developed a
      simplified essential amino acid-based profile and tested whether it could improve
      prognostication. Plasma essential amino acids and lipidomics were measured on
      1084 participants. The initial cohort included 94 normal controls and 599
      patients hospitalized due to acute/decompensated HF. The validation cohort
      included 391 HF patients. Patients were followed for composite events (death/HF
      related re-hospitalization) and were categorized into three groups: high risk
      type 1 (leucine >=145 MUM and phenylalanine >= 88.9 MUM), high risk type 2
      (leucine < 81.2 MUM), and low risk (other). Types 1 and 2 were associated with
      higher event rates [hazard ratio (95% confidence intervals) = 1.88 (1.27-2.79)
      and 7.71 (4.97-11.9), respectively, p < 0.001]. Compared to the low-risk group,
      both types of high-risk patients were older and had lower blood pressure and
      estimated glomerular filtration rates, but higher B-type natriuretic peptides
      (BNP). In addition, type 1 was associated with more incompletely metabolized
      lipids in the blood; type 2 patients had lower body mass indexes, rates of using
      guideline-based medications, and levels of cholesterol, hemoglobin, and albumin.
      The prognostic value of types 1 and 2 remained significant after adjusting for
      age, BNP and other risk factors. The value of using high-risk types for prognosis
      was confirmed in the validation cohort. In conclusion, simplified essential amino
      acid-based profiling identified two high-risk populations and provided metabolic
      information and prognostic value additive to traditional risk factors.

PMID- 30203394
TI  - Development of Activity-Based Proteomic Probes for Protein Citrullination.
AB  - Protein arginine deiminases (PADs) catalyze the post-translational deimination of
      peptidyl arginine to form peptidyl citrulline. This modification is increased in
      multiple inflammatory diseases and in certain cancers. PADs regulate a variety of
      signaling pathways including apoptosis, terminal differentiation, and
      transcriptional regulation. Activity-based protein profiling (ABPP) probes have
      been developed to understand the role of the PADs in vivo and to investigate the
      effect of protein citrullination in various pathological conditions. Furthermore,
      these ABPPs have been utilized as a platform for high-throughput inhibitor
      discovery. This review will showcase the development of ABPPs targeting the PADs.
      In addition, it provides a brief overview of PAD structure and function along
      with recent advances in PAD inhibitor development.

PMID- 30203395
TI  - The Overlooked Glycan Components of the Cryptococcus Capsule.
AB  - Pathogenic species of Cryptococcus kill approximately 200,000 people each year.
      The most important virulence mechanism of C. neoformans and C. gattii, the
      causative agents of human and animal cryptococcosis, is the ability to form a
      polysaccharide capsule. Acapsular mutants of C. neoformans are avirulent in mice
      models of infection, and extracellularly released capsular polysaccharides are
      deleterious to the immune system. The principal capsular component in the
      Cryptococcus genus is a complex mannan substituted with xylosyl and glucuronyl
      units, namely glucuronoxylomannan (GXM). The second most abundant component of
      the cryptococcal capsule is a galactan with multiple glucuronyl, xylosyl, and
      mannosyl substitutions, namely glucuronoxylomannogalactan (GXMGal). The
      literature about the structure and functions of these two polysaccharides is
      rich, and a number of comprehensive reviews on this topic are available. Here, we
      focus our discussion on the less explored glycan components associated with the
      cryptococcal capsule, including mannoproteins and chitin-derived molecules. These
      glycans were selected for discussion on the basis that i) they have been
      consistently detected not only in the cell wall but also within the cryptococcal
      capsular network and ii) they have functions that impact immunological and/or
      pathogenic mechanisms in the Cryptococcus genus. The reported functions of these
      molecules strongly indicate that the biological roles of the cryptococcal capsule
      go far beyond the well-known properties of GXM and GXMGal.

PMID- 30203396
TI  - Activity-Based Protein Profiling at the Host-Pathogen Interface.
AB  - Activity-based protein profiling (ABPP) is a technique for selectively detecting
      reactive amino acids in complex proteomes with the aid of chemical probes. Using
      probes that target catalytically active enzymes, ABPP can rapidly define the
      functional proteome of a biological system. In recent years, this approach has
      been increasingly applied to globally profile enzymes active at the host-pathogen
      interface of microbial infections. From in vitro co-culture systems to animal
      models of infection, these studies have revealed enzyme-mediated mechanisms of
      microbial pathogenicity, host immunity, and metabolic adaptation that dynamically
      shape pathogen interactions with the host.

PMID- 30203397
TI  - Correction to: Hormonal contraceptives and risk of ischemic stroke in women with
      migraine: a consensus statement from the European Headache Federation (EHF) and
      the European Society of Contraception and Reproductive Health (ESC).
AB  - Following the publication of this article [1], the authors noticed that they
      incorrectly reported the Absolute risk of ischemic stroke in women aged 20 to 44
      years in relation to the use of hormonal contraception and migraine status due to
      a miscalculation. They apologize for this misreported result.

PMID- 30203399
TI  - Insight into the surfactin production of Bacillus velezensis B006 through
      metabolomics analysis.
AB  - Bacillus velezensis B006 is a biocontrol agent which functions through effective
      colonization and surfactin production. To reveal the surfactin-producing
      mechanism, gas chromatography-mass spectrometry based untargeted metabolomics was
      performed to compare the metabolite profiles of strain B006 grown in industrial
      media M3 and M4. Based on the statistical and pathway topology analyses, a total
      of 31 metabolites with a fold change of less than - 1.0 were screened as the
      significantly altered metabolites, which distributed in 15 metabolic pathways.
      Fourteen amino acids involving in the metabolisms of alanine/aspartate/glutamate,
      glycine/serine/threonine, arginine/proline, glutathione/cysteine/methionine and
      valine/leucine/isoleucine as well as succinic acid in TCA cycle were identified
      to be the hub metabolites. Aminoacyl-tRNA biosynthesis, glycerolipid metabolism,
      and pantothenate/CoA biosynthesis also contributed to surfactin production. To
      the best of our knowledge, this study is the first to investigate the metabolic
      pathways of B. velezensis on surfactin production, and will benefit the
      optimization of commercial fermentation for higher surfactin yield.

PMID- 30203398
TI  - Myofascial trigger points in migraine and tension-type headache.
AB  - BACKGROUND: A myofascial trigger point is defined as a hyperirritable spot in
      skeletal muscle that is associated with a hypersensitive palpable nodule in a
      taut band. It has been suggested that myofascial trigger points take part in
      chronic pain conditions including primary headache disorders. The aim of this
      narrative review is to present an overview of the current imaging modalities used
      for the detection of myofascial trigger points and to review studies of
      myofascial trigger points in migraine and tension-type headache. FINDINGS:
      Different modalities have been used to assess myofascial trigger points including
      ultrasound, microdialysis, electromyography, infrared thermography, and magnetic
      resonance imaging. Ultrasound is the most promising of these modalities and may
      be used to identify MTrPs if specific methods are used, but there is no precise
      description of a gold standard using these techniques, and they have yet to be
      evaluated in headache patients. Active myofascial trigger points are prevalent in
      migraine patients. Manual palpation can trigger migraine attacks. All
      intervention studies aiming at trigger points are positive, but this needs to be
      further verified in placebo-controlled environments. These findings may imply a
      causal bottom-up association, but studies of migraine patients with comorbid
      fibromyalgia syndrome suggest otherwise. Whether myofascial trigger points
      contribute to an increased migraine burden in terms of frequency and intensity is
      unclear. Active myofascial trigger points are prevalent in tension-type headache
      coherent with the hypothesis that peripheral mechanisms are involved in the
      pathophysiology of this headache disorder. Active myofascial trigger points in
      pericranial muscles in tension-type headache patients are correlated with
      generalized lower pain pressure thresholds indicating they may contribute to a
      central sensitization. However, the number of active myofascial trigger points is
      higher in adults compared with adolescents regardless of no significant
      association with headache parameters. This suggests myofascial trigger points are
      accumulated over time as a consequence of TTH rather than contributing to the
      pathophysiology. CONCLUSIONS: Myofascial trigger points are prevalent in both
      migraine and tension-type headache, but the role they play in the pathophysiology
      of each disorder and to which degree is unclarified. In the future, ultrasound
      elastography may be an acceptable diagnostic test.

PMID- 30203402
TI  - A Little Bit of Cancer is Still Cancer: Is it Time for Lymph Node Micrometastases
      in Non-small Cell Lung Cancer to Get Their Due?

PMID- 30203400
TI  - RUNX2 Promotes Malignant Progression in Glioma.
AB  - Glioblastoma (GBM) is the most aggressive and lethal form of brain tumor.
      However, therapeutic strategies against malignant gliomas have not been
      completely established. Runt-related transcription factor 2 (Runx2) is an
      essential gene for skeletal development but its regulatory role in the malignant
      progression of glioma remains unclear. Here we investigated expression levels of
      RUNX2 in glioma tissues and its regulatory effects on aberrant growth of glioma
      cells. RUNX2 mRNA levels were higher in GBM tissues than that of normal brains or
      low-grade gliomas. RUNX2 protein was detected in five out of seven human GBM cell
      lines and its level was positively correlated with proliferative capacity. Stable
      transduction of dominant-negative Runx2 in rat-derived C6 glioma cells not only
      inhibited the promoter activity containing Runx2 response element, but also
      decreased mRNA expression levels of Runx2 target genes, such as Mmp13 and Spp1,
      as well as the proliferative capacity. Furthermore, transient introduction of
      Runx2-targeted siRNAs into C6 glioma cells significantly decreased mRNA
      expression levels of Mmp13 and Spp1 and the proliferative capacity. Furthermore,
      Runx2 knockdown suppressed both Ccnd1 mRNA expression and activation of the Ccnd1
      promoter by forskolin, a PKA-activating reagent, in C6 glioma cells. Our results
      demonstrate that cross-talk between cAMP/PKA signaling and RUNX2 promotes a
      malignant phenotype of glioma cells.

PMID- 30203403
TI  - Patient Selection for Active Surveillance in the Multi-parametric Magnetic
      Resonance Imaging Era: A Step Forward in a Rapidly Evolving Field.

PMID- 30203401
TI  - Time-Course Changes and New Expressions of MIP-3alpha and Its Receptor, CCR6, in
      the Gerbil Hippocampal CA1 Area Following Transient Global Cerebral Ischemia.
AB  - Macrophage inflammatory protein-3alpha (MIP-3alpha) and its sole receptor, CCR6,
      play pivotal roles in neuroinflammatory processes induced by brain ischemic
      insults. In this study, we investigated transient ischemia-induced changes in MIP
      3alpha and CCR6 protein expressions in the hippocampal CA1 area following 5 min
      of transient global cerebral ischemia (tgCI) in gerbils. Both MIP-3alpha and CCR6
      immunoreactivities were very strongly expressed in pyramidal neurons of the CA1
      area from 6 h to 1 day after tgCI and were hardly shown 4 days after tgCI. In
      addition, strong MIP-3alpha immunoreactivity was newly expressed in astrocytes 6
      h after tgCI. These results indicate that tgCI causes apparent changes in MIP
      3alpha and CCR6 expressions in pyramidal neurons and astrocytes in the
      hippocampal CA1 area and suggest that tgCI-induced changes in MIP-3alpha and CCR6
      expressions might be closely associated with neuroinflammatory processes in brain
      ischemic regions.

PMID- 30203404
TI  - Defining the Need for Imaging and Biopsy After Mastectomy.
AB  - BACKGROUND: The proportion of patients eligible for breast-conservation therapy
      (BCT) yet opting for mastectomy is increasing. This decision is often driven by
      the desire to eliminate future screening and/or biopsy of the remaining breast or
      breasts. This study investigated the incidence of post-mastectomy imaging and
      biopsy. METHODS: A retrospective review of all unilateral mastectomy (UM) and
      bilateral mastectomy (BM) cases managed at a single institution was undertaken.
      Post-mastectomy imaging and biopsy rates were determined. RESULTS: Between 2009
      and 2015, 185 UM and 200 BM cases managed for breast cancer were identified. The
      mean follow-up period was 30 months (range 3-75 months). For the patients with
      UM, imaging studies and biopsies done on the contralateral side were excluded
      given the standard of care for continued surveillance of the contralateral
      breast. Of the 185 UM patients, 19 (10%) underwent ipsilateral imaging (all
      ultrasounds) for physical examination findings, 11 (6%) underwent biopsy, and 2
      (1%) had malignant findings. Of the 200 BM patients, 31 (15.5%) required imaging
      (29 ultrasounds and 2 MRIs), with 76% of the ultrasounds performed on the side
      with previous cancer. Subsequently, 16 (8%) of the BM patients had biopsy, with
      11 (69%) of the 16 biopsies performed on the ipsilateral side. Three (1.5%) of
      the biopsies done on ipsilateral side demonstrated malignancy, whereas all the
      contralateral biopsies were benign. CONCLUSIONS: For 10-15.5% of patients who
      undergo mastectomy, either UM or BM, subsequent imaging is required, whereas 6-8%
      undergo biopsy. The yield of malignancy is low, approximately 1%. Thus, after
      mastectomy, the need for imaging and biopsy is not eliminated. This information
      is critical for patient understanding and expectation related to surgical
      decision making.

PMID- 30203405
TI  - Correction to: Why Do Reoperation Rates Vary So Much After Lumpectomy for Breast
      Cancer? Examining the Reoperation Puzzle.
AB  - In the original article the correct citation for where Massachusetts General
      Hospital (MGH) is mentioned throughout the text.

PMID- 30203406
TI  - Lymph Node Micrometastasis Prognosticates Survival for Patients with Stage 1
      Bronchogenic Adenocarcinoma.
AB  - BACKGROUND: This study aimed to investigate the significance of lymph node
      micrometastasis (LNMM) in the lung cancer nodal categories. METHODS: Between 1
      January 2009 and 31 December 2013, 589 patients with suspected c-stage 1 and p-T1
      2aN0-1M0 lung adenocarcinoma were enrolled in this study. The study evaluated
      LNMM with cytokeratin (AE1/AE3) and transcription factor-1 (TTF1) (8G7G3/1)
      expression by immunohistochemistry. Recurrence-free survival (RFS) and overall
      survival (OS) were compared among the T1-2aN0-1M0 patients stratified by the new
      N categories. RESULTS: From 589 patients, 7892 removed lymph nodes were examined,
      and LNMM was observed in 55 (9.3%) of the patients. The patients without LNMM or
      N1 had the best RFS (5-year rate: 80% vs 25%; P < 0.001) and OS (5-year rate: 87%
      vs 43%; P < 0.001), followed by the patients with LNMM, compared with those in
      the N1 category (RFS: 5-year rate, 25% vs 8%; P = 0.010; OS: 5-year rate, 43% vs
      20%; P = 0.009). Similarly, this trend was observed when patients were subdivided
      into the T1 and T2a categories. Multivariate analysis showed that the new N
      categories with the addition of LNMM were an independent prognostic factor. This
      result also was noticed in all subgroups. CONCLUSIONS: The findings showed LNMM
      to be clinically significant as a risk factor for lung cancer. Clinicians should
      consider LNMM when estimating N categories to determine prognosis and the best
      treatment strategy.

PMID- 30203407
TI  - Prognostic Impact of Immune-Related Gene Expression in Preoperative Peripheral
      Blood from Gastric Cancer Patients.
AB  - BACKGROUND: Anti-PD-1 therapy has shown a promising clinical outcome in gastric
      cancer (GC). We evaluated the clinical significance of systemic immune-related
      gene expression in GC patients who underwent surgery. METHODS: The correlation
      between the preoperative PD-1, PD-L1, and CD8 mRNA levels in peripheral blood
      (PB) and clinicopathological factors, including survival, in 372 GC patients was
      evaluated using quantitative RT-PCR. PD-1- and PD-L1-expressing cells were
      identified by flow cytometric analysis. RESULTS: The PD-1, PD-L1, and CD8 mRNA
      levels in GC patients were significantly higher than those in normal controls,
      respectively (all P < 0.0001). The levels of each gene were positively correlated
      with those of the other two genes (all P < 0.0001). GC patients with low PD-1,
      high PD-L1, and low CD8 mRNA levels had significantly poorer overall survival
      (OS) than those with high PD-1, low PD-L1, and high CD8 mRNA levels, respectively
      (P < 0.01, P < 0.05, and P < 0.05, respectively). Multivariate analysis showed
      that low PD-1 and high PD-L1 mRNA levels were independent poor prognostic factors
      for OS (PD-1: HR 2.38, 95% CI 1.27-4.78, P < 0.01; PD-L1: HR 1.81, 95% CI 1.15
      2.78, P < 0.05). PD-1 and PD-L1 expression occurred on T cells (> 90%) and T
      cells or monocytes (> 70%), respectively. CONCLUSIONS: The PD-1, PD-L1, and CD8
      mRNA levels in preoperative PB reflected the anti-tumour immune response, and the
      low PD-1 and high PD-L1 mRNA levels in PB were independent poor prognostic
      markers in GC patients who underwent surgery.

PMID- 30203408
TI  - Kir2.1 Channel Regulation of Glycinergic Transmission Selectively Contributes to
      Dynamic Mechanical Allodynia in a Mouse Model of Spared Nerve Injury.
AB  - Neuropathic pain is a chronic debilitating symptom characterized by spontaneous
      pain and mechanical allodynia. It occurs in distinct forms, including brush
      evoked dynamic and filament-evoked punctate mechanical allodynia. Potassium
      channel 2.1 (Kir2.1), which exhibits strong inward rectification, is and
      regulates the activity of lamina I projection neurons. However, the relationship
      between Kir2.1 channels and mechanical allodynia is still unclear. In this study,
      we first found that pretreatment with ML133, a selective Kir2.1 inhibitor, by
      intrathecal administration, preferentially inhibited dynamic, but not punctate,
      allodynia in mice with spared nerve injury (SNI). Intrathecal injection of low
      doses of strychnine, a glycine receptor inhibitor, selectively induced dynamic,
      but not punctate allodynia, not only in naive but also in ML133-pretreated mice.
      In contrast, bicuculline, a GABAA receptor antagonist, induced only punctate, but
      not dynamic, allodynia. These results indicated the involvement of glycinergic
      transmission in the development of dynamic allodynia. We further found that SNI
      significantly suppressed the frequency, but not the amplitude, of the glycinergic
      spontaneous inhibitory postsynaptic currents (gly-sIPSCs) in neurons on the
      lamina II-III border of the spinal dorsal horn, and pretreatment with ML133
      prevented the SNI-induced gly-sIPSC reduction. Furthermore, 5 days after SNI,
      ML133, either by intrathecal administration or acute bath perfusion, and
      strychnine sensitively reversed the SNI-induced dynamic, but not punctate,
      allodynia and the gly-sIPSC reduction in lamina IIi neurons, respectively. In
      conclusion, our results suggest that blockade of Kir2.1 channels in the spinal
      dorsal horn selectively inhibits dynamic, but not punctate, mechanical allodynia
      by enhancing glycinergic inhibitory transmission.

PMID- 30203409
TI  - Models of Replicator Proliferation Involving Differential Replicator Subunit
      Stability.
AB  - Several models for the origin of life involve molecules that are capable of self
      replication, such as self-replicating polymers composed of RNA or DNA or amino
      acids. Here we consider a hypothetical replicator (AB) composed of two subunits,
      A and B. Programs written in Python and C programming languages were used to
      model AB replicator abundance as a function of cycles of replication
      (iterations), under specified hypothetical conditions. Two non-exclusive models
      describe how a reduced stability for B relative to A can have an advantage for
      replicator activity and/or evolution by generating free A subunits. In model 1,
      free A subunits associate with AB replicators to create AAB replicators with
      greater activity. In simulations, reduced stability of B was beneficial when the
      replication activity of AAB was greater than two times the replication activity
      of AB. In model 2, the free A subunit is inactive for some number of iterations
      before it re-creates the B subunit. A re-creates the B subunit with an equal
      chance of creating B or B', where B' is a mutant that increases AB' replicator
      activity relative to AB. In simulations, at moderate number of iterations (< 15),
      a shorter survival time for B is beneficial when the stability of B is greater
      than the inactive time of A. The results are consistent with the hypothesis that
      reduced stability for a replicator subunit can be advantageous under appropriate
      conditions.

PMID- 30203410
TI  - Investigating the Kinetics of Montmorillonite Clay-Catalyzed Conversion of
      Anthracene to 9,10-Anthraquinone in the Context of Prebiotic Chemistry.
AB  - Carbonaceous meteorites contributed polycyclic aromatic hydrocarbons (PAHs) to
      the organic inventory of the primordial Earth where they may have reacted on
      catalytic clay mineral surfaces to produce quinones capable of functioning as
      redox species in emergent biomolecular systems. To address the feasibility of
      this hypothesis, we assessed the kinetics of anthracene (1) conversion to 9,10
      anthraquinone (2) in the presence of montmorillonite clay (MONT) over the
      temperature range 25 to 250  degrees C. Apparent rates of conversion were
      concentration independent and displayed a sigmoidal relationship with
      temperature, and conversion efficiencies ranged from 0.027 to 0.066%. Conversion
      was not detectable in the absence of MONT or a sufficiently high oxidation
      potential (in this case, molecular oxygen (O2)). These results suggest a scenario
      in which meteoritic 1 and MONT interactions could yield biologically important
      quinones in prebiotic planetary environments.

PMID- 30203412
TI  - Pulmonary haemodynamics and right ventricular function in cemented vs uncemented
      total hip arthroplasty-A randomized trial.
AB  - BACKGROUND: Bone cement implantation syndrome (BCIS) is a feared complication in
      orthopaedic surgery with a huge impact on post-operative morbidity. In this
      randomized trial, we evaluated the effects of bone cement on pulmonary and
      systemic haemodynamics in patients receiving either cemented or uncemented hip
      arthroplasty for isolated femoral neck fracture. METHODS: Twenty-two patients
      were randomized to receive either cemented (n = 10) or uncemented (n = 12) total
      hip arthroplasty. Surgery was performed under total intravenous anaesthesia in
      the lateral position. All patients were catheterized with radial- and pulmonary
      artery catheters, for continuous measurements of mean arterial pressure (MAP),
      pulmonary arterial pressure (PAP), cardiac output, right ventricular (RV) end
      diastolic volume (RVEDV) and RV ejection fraction (RVEF). Haemodynamic
      measurements and blood gas analyses were performed after induction of
      anaesthesia, during surgery before and immediately after bone cementation and
      prosthesis insertion, 10 and 20 minutes after insertion and during skin closure.
      RESULTS: Pulmonary vascular resistance index (PVRI) increased during and after
      prosthesis insertion by 45% and 20% in the cemented and uncemented group,
      respectively (P < 0.005). Systolic and mean PAP increased by 18% and 17% in the
      cemented group, which was not seen in the uncemented group (P < 0.001). There was
      a trend for a more pronounced fall in RVEF in the cemented group, while there
      were no differences in cardiac output or stroke volume between groups.
      CONCLUSION: The use of bone cement in total hip arthroplasty increases pulmonary
      vascular resistance and the afterload of the RV with potentially negative effects
      on RV performance.

PMID- 30203413
TI  - Myasthenia gravis unmasked by imatinib.

PMID- 30203411
TI  - T-Cell Clustering in Neoplastic Follicles of Follicular Lymphoma.
AB  - The nonneoplastic microenvironment is abundant in follicular lymphoma. Its
      composition has been reported to be associated with the course of the disease.
      Lack of animal models hampers studies of interaction between lymphoma and
      bystander cells. We aimed to identify indicators of cellular interaction
      exemplified by nonrandom distribution of cell types within neoplastic follicles.
      Physiological germinal centers and follicles in follicular lymphoma were stained
      to identify macrophages, all T, follicular T-helper, dendritic and B cells.
      Density of cell types and cell distribution (spatial point pattern) were analyzed
      by digital image analysis. The density of all T, follicular T-helper and
      dendritic cells was higher in the dark zone than in the light zone of
      physiological germinal centers. Densities of cell types in follicular lymphoma
      were intermediate between the light and the dark zone. All cell types analyzed
      showed a completely random spatial distribution pattern within the dark and the
      light zone, respectively. In follicular lymphoma B cells and macrophages
      displayed complete spatial randomness. In contrast, all T cells, follicular T
      helper cells and dendritic cells showed clustering of each individual cell type
      within a radius of 6-10 MUm in the lymphoma. We conclude that the distribution of
      nonneoplastic cells within follicles of follicular lymphoma is not random. T
      cells and dendritic cells form clusters within the follicles, suggestive of sites
      of interaction between microenvironment and lymphoma cells. These clusters might
      help to understand the interaction of lymphoma cells with the microenvironment
      and might provide a structure for therapeutic intervention.

PMID- 30203414
TI  - A novel bayesian multiple testing approach to deregulated miRNA discovery
      harnessing positional clustering.
AB  - MicroRNAs (miRNAs) are small non-coding RNAs that function as regulators of gene
      expression. In recent years, there has been a tremendous interest among
      researchers to investigate the role of miRNAs in normal as well as in disease
      processes. To investigate the role of miRNAs in oral cancer, we analyse
      expression levels of miRNAs to identify miRNAs with statistically significant
      differential expression in cancer tissues. In this article, we propose a novel
      Bayesian hierarchical model of miRNA expression data. Compelling evidence has
      demonstrated that the transcription process of miRNAs in the human genome is a
      latent process instrumental for the observed expression levels. We take into
      account positional clustering of the miRNAs in the analysis and model the latent
      transcription phenomenon nonparametrically by an appropriate Gaussian process.
      For the purpose of testing, we employ a novel Bayesian multiple testing method
      where we mainly focus on utilizing the dependence structure between the
      hypotheses for better results, while also ensuring optimality in many respects.
      Indeed, our non-marginal method yielded results in accordance with the underlying
      scientific knowledge which are found to be missed by the very popular Benjamini
      Hochberg method.

PMID- 30203415
TI  - A meta-analysis identified genes responsible for distinct immune responses to
      trivalent inactivated and live attenuated influenza vaccines.
AB  - Vaccinations are the cornerstone of influenza prevention strategies. We carried
      out a meta-analysis of the messenger RNA expression profiles from recipients of
      trivalent inactivated vaccines (TIV) or live attenuated vaccines (LAIV) to
      determine the different recipients' responses to these two types of vaccines,
      which may provide information to improve the design of future improved vaccines.
      We executed meta-analysis on these datasets using a random-effects model and
      identified 191 and 195 differentially expressed genes in TIV and LAIV,
      respectively, with an false discovery rate <0.05. The genes significantly
      upregulated by TIV were associated with both the innate immune response and the
      humoral immune response, whereas LAIV mainly activated the innate immune system.
      The identified genes that responsible for the immune difference between LAIV and
      TIV might provide new information to improve current vaccines to have better
      efficacy in children, adults, and the elderly.

PMID- 30203416
TI  - Juveniles with a history of violent behavior show cognitive performance and
      electrophysiology consistent with inhibitory control and emotional feedback
      processing problems.
AB  - Inhibitory control and the effects of negative emotional feedback were
      investigated in adolescents with a history of violent behavior and normal
      adolescents using the Taylor Aggression Paradigm (TAP), a task simulating real
      situations of social interaction to elicit aggressive behavior and negative
      emotions, with concurrent event related potential recordings. The Reactive
      Proactive Aggression Questionnaire (RPAQ), the Barratt Impulsiveness Scale (BIS)
      and the Negative Mood Regulation (NMR) Scale were also presented. These showed
      that reactive scores, proactive scores, and BIS scores were all significantly
      higher for the violent offender group whereas scores from the NMR scale were
      significantly lower for this group. In the TAP, the violent offender group chose
      significantly higher levels of punishment, indicative of both higher proactive
      and higher reactive aggression, for their opponent than did the control group.
      The ERP data showed the N2 amplitude for the decision phase, indicative of
      inhibitory control, was lower for the violent offender group than for the control
      group, with mediation analysis showing that the N2 component was related to
      proactive aggression. The decision-related negativity and the feedback-related
      negativity in the result phase were also both lower for the violent offender
      group than for the control group. Adolescent violent offenders showed higher
      levels of aggressive behavior than normal adolescents. This is associated with
      both worse inhibitory control and worse negative emotion regulation.
      Investigation of common factors underlying these processes, in conjunction with
      possible ways in which they might be improved, should be a priority for future
      work.

PMID- 30203417
TI  - Improving patient prioritization during hospital-homecare transition: A pilot
      study of a clinical decision support tool.
AB  - Patient admission to homecare is a complex process. Medicare policy requires that
      all patients receive a first home visit within 48 hr after the referral is
      received at the homecare agency. For unstable or high risk patients, waiting 48
      hr to be seen by homecare nurses may not be safe. In this pilot study we tested
      an innovative clinical decision support tool (called PREVENT), designed to
      identify patients who may need to be prioritized for early homecare visits. The
      study was conducted in 2016 at a large homecare agency in the Northeastern US
      with 176 patients admitted to homecare from the hospital. In the control phase (n
      = 90 patients), we calculated the PREVENT priority score (indicative of high or
      medium/low first nursing visit priority) but did not share the score with the
      homecare intake nurses who influence visit scheduling. In the experimental phase,
      the PREVENT score was shared with the homecare intake nurses (n = 86 patients).
      During the experimental phase, high-risk patients received their first homecare
      nursing visit about one-half a day sooner than in the control phase (1.8 days vs.
      2.2 days). Rehospitalizations from homecare decreased by 9.4% between the control
      (21.1%) and experimental phases (11.7%). This pilot study of patient
      prioritization showed promising results: high priority patients received their
      first homecare visit sooner and overall rehospitalization rates were lower.

PMID- 30203418
TI  - Iron overload is correlated with impaired autologous stem cell mobilization and
      survival in acute myeloid leukemia.
AB  - BACKGROUND: Patients with acute myeloid leukemia (AML) undergoing consolidation
      with autologous stem cell transplantation (ASCT) depend on the successful
      mobilization of peripheral blood stem cells. However, the factors affecting the
      mobilization potential in AML patients and, in particular, the effect of
      transfusion-related iron overload on peripheral blood stem cell mobilization are
      largely unknown. STUDY DESIGN AND METHODS: We investigated the association of
      varying levels of iron overload and stem cell mobilization efficacy in
      consecutive AML patients after two induction cycles. RESULTS: A total of 113 AML
      patients in early first complete remission underwent the mobilization procedure.
      While 84 (74.3%) patients had serum ferritin levels exceeding 1000 MUg/L, 26
      (23.0%) patients had levels even higher than 2000 MUg/L. Iron overload correlated
      with the number of preceding red blood cell transfusions and inversely correlated
      with circulating CD34+ cell levels (p = 0.04) at apheresis. Finally, the median
      progression-free and overall survival rates of patients with ferritin levels of
      higher than 2000 MUg/L were shorter with 332 days versus 2156 days (p = 0.04) and
      852 days versus 2235 days (p = 0.04), respectively. CONCLUSION: Our data suggest
      that transfusion-related iron overload is suppressing the mobilization potential
      and is associated with inferior outcome in AML.

PMID- 30203419
TI  - Lineage switch from acute myeloid leukemia to T cell/myeloid mixed phenotype
      acute leukemia: First report of an adult case.

PMID- 30203420
TI  - How Valid Is Tomographic Ultrasound Imaging in Diagnosing Levator and Anal
      Sphincter Trauma?
AB  - OBJECTIVES: Three-/four-dimensional translabial ultrasound (US) is increasingly
      used to image the levator ani and anal sphincters, especially in the form of
      tomographic US. The aim of the study was to evaluate the validity of these
      published methods. METHODS: This work was a retrospective analysis of datasets of
      172 nulliparous women who attended 2 tertiary urogynecologic centers for symptoms
      of pelvic floor dysfunction between June 2012 and September 2016. All patients
      had a standardized interview, clinical examination, and 4-dimensional translabial
      US examination. An evaluation of volume data was performed by the first author,
      who was blinded against all clinical data, including parity. An assessment for
      levator avulsion and anal sphincter defects was performed using stored US volume
      data. RESULTS: Data sets of 162 and 153 nulliparous women were available for
      levator and anal sphincter assessments, respectively. On the assessment by the
      first author, a complete avulsion was diagnosed in 3 nulliparas. On a review by 2
      senior authors, 1 was judged as positive and the other 2 as normal. On the
      sphincter assessment, 2 significant external anal sphincter defects were
      detected. On the review, 1 was judged as false-positive. The second was judged as
      highly abnormal by all authors. Therefore, 1 nullipara each was diagnosed with
      avulsion and a significant external anal sphincter defect. CONCLUSIONS: Published
      diagnostic criteria for levator avulsion and external anal sphincter trauma on
      tomographic US imaging are highly unlikely to result in false-positive findings.
      This finding supports the clinical validity of this method.

PMID- 30203421
TI  - ICS educational module: Cystometry in children.
AB  - AIMS: To introduce the standard procedure of cystometry and interpretation of the
      results in children. METHODS: The literature on cystometry in children in PubMed
      for the last 20 years was reviewed. The updated knowledge regarding indication,
      preparation, technique, and interpretation of cystometry in children were
      summarized. RESULTS: Filling cystometry is the core content of a paediatric
      urodynamic study. In this section, the technique for performing cystometry is
      introduced in details. Emphasis is placed on correctly setting up the equipment
      according to ICS and ICCS guidelines, using appropriate terminology, providing
      indications for its performance with specific considerations for children, and
      proper interpretation of results. CONCLUSIONS: Cystometry can be used in children
      including newborn to evaluate lower urinary tract dysfunction.

PMID- 30203422
TI  - Leptin attenuates oxidative stress and neuronal apoptosis in hyperglycemic
      condition.
AB  - One of the main pathological mechanisms of neurotoxicity in diabetic situation is
      oxidative stress promoted by hyperglycemia. It has been shown that leptin has
      neuroprotective effects and may provide neuronal survival signals. This study was
      designed to reveal the possible neuroprotective effects of leptin in
      hyperglycemic conditions. Pheochromocytoma (PC12) cell viability was assessed via
      the MTT test. Cellular reactive oxygen species (ROS) generation was determined by
      DCFH-DA analysis. The malondialdehyde (MDA) and glutathione (GSH) levels were
      measured in high-glucose-treated PC12 cells with and without leptin cotreatment.
      Western blotting was performed to measure apoptosis markers (Cleaved caspase-3
      and Bax/Bcl2 ratio). Elevation of glucose levels (100 mmol/L) consecutively
      increased intracellular ROS and MDA level, and apoptosis in PC12 cells after 24 h
      leptin administration (12 and 24 nmol/L) decreased the high-glucose-induced cell
      toxicity, caspase-3 activation, and Bax/Bcl-2 ratio. Also, cotreatment with
      leptin (12 and 24 nmol/L) significantly reduced oxidative damage to PC12 cells in
      high-glucose condition, as reflected by the diminution in MDA and ROS levels and
      the increase in GSH content. Our finding demonstrates that leptin has protective
      effects against hyperglycemia-induced neural damage. This could be related to the
      attenuation of oxidative stress and neural apoptosis.

PMID- 30203423
TI  - Rural Primary Care Providers' Experiences and Knowledge Regarding LGBTQ Health in
      a Midwestern State.
AB  - PURPOSE: Health disparities among LGBTQ people have been documented across
      various settings and recent research has indicated that many disparities are
      heightened in the context of rurality. Among these disparities is the decreased
      rate of primary care utilization by rural LGBTQ individuals. Understanding and
      addressing provider knowledge and attitudes related to LGBTQ health provides a
      relevant avenue for addressing underutilization. METHODS: The study presented was
      a mail-out survey regarding rural primary care providers' knowledge and
      experiences regarding LGBTQ health. Publicly available records were compiled to
      recruit a total sample of 113 primary care providers, at a response rate of
      19.8%. FINDINGS: A majority of respondents reported experience providing care to
      LGBTQ patients, while only slightly over half had received LGBTQ health
      education. Data analyses revealed significant associations between reported
      experiences and patient characteristics including religion, religiousness, age,
      length of time practicing in current provider role, and gender identity. Provider
      knowledge of LGBTQ health varied greatly across the items assessed. Provider
      profession (physician, nurse practitioner, physician assistant) and length of
      current county residence were significantly predictive of LGBTQ knowledge scores.
      CONCLUSION: Results provide insight into rural health care for LGBTQ people.
      Preeminent findings were: (1) an existing need for LGBTQ health education, (2)
      variation in knowledge across content areas, and (3) association between
      knowledge, profession, and length of current county residence. Promotion of rural
      LGBTQ health may benefit by addressing identified gaps in current care.

PMID- 30203424
TI  - Essential role of ryanodine receptor 2 phosphorylation in the effect of azumolene
      on ventricular arrhythmia vulnerability in a rabbit heart model.
AB  - INTRODUCTION: Following long-duration ventricular fibrillation (LDVF),
      reinitiation of ventricular fibrillation (VF) poses a major challenge during
      resuscitation. Ryanodine receptor 2 (RyR2) becomes dysfunctional following VF.
      The relationship between LDVF, RyR2 modulation, and ventricular refibrillation,
      as well as the role of RyR2 phosphorylation, remains unknown. METHODS:
      Langendorff-perfused rabbit hearts were subjected to global ischemia and treated
      with azumolene (or vehicle alone in controls) upon reperfusion. After electrical
      induction of an initial LDVF episode, each heart was further stimulated
      electrically to assess reinducibility of VF. Myocardial calcium dynamics were
      assessed by optical mapping. RyR2 phosphorylation in left ventricular tissue
      extracts was analyzed by Western blot analysis. RESULTS: Fewer episodes of
      refibrillation (lasting >= 10 seconds) were induced in azumolene-treated hearts
      than in controls (P = 0.01); however, this reduction in refibrillation was
      abrogated in the presence of the protein kinase A inhibitor H89. Spontaneous
      calcium elevation was significantly lower in azumolene-treated hearts than in
      control hearts ( P = 0.002) and in hearts pretreated with H89 before azumolene (
      P = 0.01). RyR2 phosphorylation at Ser2808 was higher in hearts subjected to LDVF
      than in non-VF hearts ( P = 0.029), while no significant difference was found at
      Ser2814. Pretreatment with H89 led to significantly less RyR2 phosphorylation at
      Ser2808 ( P = 0.04) after LDVF, while pretreatment with KN93 or azumolene alone
      showed no effects on RyR2 phosphorylation. CONCLUSION: Ventricular refibrillation
      following LDVF was reduced by azumolene, which also improves calcium dynamics.
      RyR2 phosphorylation at Ser2808 is a prerequisite for the beneficial effects of
      azumolene.

PMID- 30203425
TI  - Study of gene polymorphisms as predictors of treatment efficacy and toxicity in
      patients with indolent non-hodgkin lymphomas and mantle cell lymphoma receiving
      bendamustine and rituximab.
AB  - Bendamustine is used in combination with rituximab (BR) to treat indolent non
      Hodgkin lymphomas (iNHL) and mantle cell lymphoma (MCL). The variability in
      treatment efficacy and toxicity could be related to single nucleotide
      polymorphisms (SNPs) in immune response genes. We would like to show a
      correlation between SNPs and treatment outcome in iNHL and MCL patients receiving
      BR. We investigated some SNPs that had already been associated with NHL outcome.
      Samples were genotyped for the IL2 (rs2069762), IL10 (rs1800890, rs10494879),
      VEGFA (rs3025039), IL8 (rs4073), CFH (rs1065489) and MTHFR (rs1801131) SNPs by
      allelic discrimination assays. We enrolled 70 patients that received rituximab
      375 mg/m2 and bendamustine 90 mg/m2 every 28 days, both as first-line treatment
      and >= second-line regimens. Overall response rate was 97.1% (complete response
      [CR] rate 73.9%). Treatment toxicity included grade 3-4 neutropenia (24/70
      patients), infections (21/70 patients; 1/70 grade 3), skin rash (26/70 patients;
      2/70 grade 3). After a median follow-up of 24 months we did find any correlation
      between the analysed SNPs, CR rate and PFS. However, we demonstrated an
      association between the SNP in IL2 (rs2069762) and the onset of skin rash (P =
      0.0001). Our study suggests a role for cytokine SNPs in bendamustine-related
      toxicity, which could represent a promising research field.

PMID- 30203426
TI  - S100A7, Jab1, and p27kip1 expression in psoriasis and S100A7 CRISPR-activated
      human keratinocyte cell line.
AB  - Psoriasis, a chronic immune-mediated inflammatory skin disease, is characterized
      by dysregulated keratinocyte proliferation. The EF-hand calcium binding protein
      S100A7 has been found to be overexpressed in psoriatic keratinocytes. It is know
      that S100A7 may interact with Jab1, a cofactor that stabilizes c-Jun. Jab1 is
      known to downregulate the expression of the cell cycle inhibitor p27Kip1 in some
      cancer models. In this study, we aimed to investigate the possible interaction
      between S100A7 and Jab1 and the downstream effects on p27 Kip1 expression in
      normal human keratinocyte cells transfected with S100A7 CRISPR activation plasmid
      and in archival psoriatic skin samples. Our results showed that the upregulated
      S100A7 colocalizes with Jab1 at the nuclear level in transfected cells and
      psoriatic skin samples. We also showed a differential protein expression of Jab1
      between cytoplasmic and nuclear compartments, thus suggesting Jab1 translocation
      from nucleus to cytoplasm. p27 Kip1 protein expression patterns would imply a
      translocation from nucleus and a subsequent degradation of this protein. The
      upregulation of S1007 and its interaction with Jab1 would contribute to the p27
      Kip1 -dependent impaired proliferation that characterizes psoriatic skin.

PMID- 30203427
TI  - Why do not anatomical linear lesions achieve mitral isthmus conduction block? The
      importance of epicardial connections via the Marshall bundle.

PMID- 30203429
TI  - The impact of food intake on the luminal environment and performance of oral drug
      products with a view to in vitro and in silico simulations: a PEARRL review.
AB  - OBJECTIVES: Using the type of meal and dosing conditions suggested by regulatory
      agencies as a basis, this review has two specific objectives: first, to summarize
      our understanding on the impact of food intake on luminal environment and drug
      product performance and second, to summarize the usefulness and limitations of
      available in vitro and in silico methodologies for the evaluation of drug product
      performance after food intake. KEY FINDINGS: Characterization of the luminal
      environment and studies evaluating product performance in the lumen, under
      conditions suggested by regulatory agencies for simulating the fed state, are
      limited. Various in vitro methodologies have been proposed for evaluating drug
      product performance in the fed state, but systematic validation is lacking.
      Physiologically based pharmacokinetic (PBPK) modelling approaches require the use
      of in vitro biorelevant data and, to date, have been used primarily for
      investigating the mechanisms via which an already observed food effect is
      mediated. SUMMARY: Better understanding of the impact of changes induced by the
      meal administration conditions suggested by regulatory agencies on the luminal
      fate of the drug product is needed. Relevant information will be useful for
      optimizing the in vitro test methods and increasing the usefulness of PBPK
      modelling methodologies.

PMID- 30203428
TI  - An Efficient Anti-poisoning Catalyst against SOx , NOx , and POx : P, N-Doped
      Carbon for Oxygen Reduction in Acidic Media.
AB  - Electrocatalysts are readily poisoned during the catalysis of the oxygen
      reduction reaction (ORR); even air containing traces of SOx and/or NOx
      significantly decrease the activity and the durability of H2 -O2 fuel cells. Now,
      a metal-free strategy is reported to develop an efficient anti-poisoning ORR
      catalyst, which involves the pyrolysis of PDAP-phytic acid super-molecular
      aggregate (PPSA). The pyrolyzed co-doped carbon acting as a metal-free
      electrocatalyst shows an enhanced activity for ORR in acidic medium, even under
      poisoning conditions (SOx , NOx , and POx ). Moreover, P-doping also changes the
      ORR pathway by yielding less than 4 % of H2 O2 , indicating a four-electron
      pathway whereas more than>20 % of H2 O2 was recorded for N-doped carbon
      synthesized from PDAP.

PMID- 30203431
TI  - Ethics as ritual: smoothing over moments of dislocation in biomedicine.
AB  - Applications of biomedical R&D currently imply substantial societal concerns.
      This paper explores, based on semi-structured interviews with scientists in
      Norway, how biomedical researchers experience and tackle such concerns in their
      daily work. It shows how ritualised routine responses to dislocatory moments help
      maintain order in the daily work of the interviewed scientists; they do not
      address directly but instead smooth over concerns by a ritualised way of using
      ethics. This may foreclose substantive reflection and function as a stabiliser
      for 'business as usual'. Overall, the current way of responding to concerns as
      described by the interviewees may contribute to a depoliticisation of important
      issues. The paper contributes to sociological work on ethics by linking it to
      recent discussions on Responsible Research and Innovation (RRI) and by the
      empirical research presented. The insights can also help improve science policies
      such as RRI.

PMID- 30203430
TI  - Bioresponsive Nanoparticles Targeted to Infectious Microenvironments for Sepsis
      Management.
AB  - Sepsis is a life-threatening disease resulted from a dysregulated host immune
      response to bacterial infections, continuing to cause high morbidity and
      mortality worldwide. Despite discoveries of many potential therapeutic targets,
      effective treatments of sepsis are lacking. Here, a strategy is reported to
      target infectious microenvironments (IMEs) via bioresponsive nanoparticles that
      simultaneously eliminate bacteria and alleviate the host inflammation response,
      thus managing sepsis in mice. The nanoparticle is made of copolymers sensitive to
      pH and bacterial enzymes to self-assemble into a micelle loaded with both an
      antibiotic (ciprofloxacin) and an anti-inflammatory agent ((2
      [(aminocarbonyl)amino]-5-(4-fluorophenyl)-3-thiophenecarboxamide). In addition,
      the nanoparticle is conjugated with intercellular adhesion molecule-1 antibodies
      to target IMEs. Nanoparticle targeting to IMEs and local cues as triggers to
      deliver therapeutics in on-demand manners is demonstrated using an acute lung
      bacterial infection mouse model. In the sepsis mouse model induced by peritonitis
      at a lethal dose of bacterial invasion, it is shown that concurrently targeting
      pathogens and excessive inflammation pathways is valuable to manage the sepsis.
      The study illustrates not only the development of a new delivery system but also
      the mechanism-based therapy of nanomedicine for infectious diseases.

PMID- 30203432
TI  - Influence of nutritional status on basal metabolic rates among rural
      agriculturalists of Ngilo-Ilo, East Java.
AB  - OBJECTIVES: Previous research has shown that tropical island populations have
      reduced basal metabolic rates (BMR) associated with the joint influences of heat
      stress and undernutrition. This study examines variation in BMR among an
      indigenous population of Indonesia, and compares these data with those collected
      from earlier studies in Indonesia. METHODS: Anthropometric dimensions and BMR
      were measured on a sample of 35 Indonesian adults (28 men, 7 women) from the
      rural village of Ngilo-Ilo, East Java. RESULTS: Mean measured BMRs (+/-SD) were
      1433 +/- 344 kcal/d in men and 1256 +/-257 kcal/d in women, and were not
      significantly different from estimates using the FAO/WHO/UNU predictive
      questions. Underweight individuals (BMIs <18.5 kg/m2 ) had BMRs that were 7.6%
      below predicted levels, while those with BMIs >=18.5 kg/m2 had BMRs that were
      8.0% above predicted levels (P < .01). Underweight individuals also had
      significantly higher respiratory quotients (RQ = .94 vs. .89; P < .05),
      suggesting lower levels of fat oxidation. Compared to data from previous studies
      (1929-1979), men of the Ngilo-Ilo sample had similar BMIs (19.8 vs. 19.2 kg/m2 ),
      but higher BMRs, after adjusting for age and body weight (+2.1% vs. -5.6%; P <
      .05). CONCLUSIONS: Among the agriculturalists of Ngilo-Ilo, measured BMRs were
      low, but not significantly different from those predicted by the FAO/WHO/UNU
      equations. Among subjects of this sample and from earlier studies, poorer
      physical nutritional status was associated with reduced BMRs. These results
      suggest that chronic energy stress has consistently shaped metabolic function
      among Indonesian rural populations.

PMID- 30203433
TI  - Spontaneous hepaticoduodenal fistula following extended right hemihepatectomy.

PMID- 30203434
TI  - Combination chemical peels are more effective than single chemical peel in
      treatment of mild-to-moderate acne vulgaris: A split face comparative clinical
      trial.
AB  - BACKGROUND: Successful management of acne involves choosing proper medication.
      Chemical peeling is a well-known option in treatment of acne vulgaris. OBJECTIVE:
      To evaluate and compare the clinical efficacy and safety of combination chemical
      peels vs single peel in treatment of mild-to-moderate acne. METHODS: The study
      included 45 patients with mild-to-moderate acne divided into three equal groups.
      Group A underwent combination sequential peels with modified Jessner's solution
      (MJ) followed by trichloro acetic acid (TCA20%) on the right (Rt) side of the
      face vs TCA 30% on the left (Lt) side. Group B was treated by combination peels
      of salicylic (20%) mandelic (10%) (SM) mixture on the Rt half vs salicylic acid
      30% on the Lt half. Group C underwent combination sequential peeling of MJ and
      TCA on the Rt side vs SM combination peels on the Lt side. All patients received
      six sessions with 2-week intervals and followed up for 3 months after the last
      session. Side effects were reported. RESULTS: Both sides of the face showed
      significant improvement of acne lesions but improvement was significantly higher
      and earlier in sides treated by combination peels. Side effects were minimal.
      CONCLUSION: In conclusion, combination peels achieved a higher and earlier
      therapeutic response with a reasonable cost that is maintained for a relatively
      long periods than single peel. Combination sequential peels gave the best
      results.

PMID- 30203435
TI  - Job autonomy, perceptions of organizational policy, and the safety performance of
      nurses.
AB  - AIMS: This study aimed to identify the relationship between nurses' job autonomy,
      perceptions of organizational policy, and safety performance by identifying the
      safety performance predictors of nurses working in acute health care settings in
      South Korea. METHODS: Using data from a structured questionnaire, this cross
      sectional descriptive study assessed the relationship between nurses' job
      autonomy, perceptions of organizational policy, and safety performance. In 2016,
      of the 290 nurses from nine acute care hospitals in South Korea invited to
      participate in the survey, 254 successfully did. Using cross-sectional data,
      characteristics of hospitals and nurses were analysed with t tests, one-way
      analyses of variance, Pearson correlations, and regression models. RESULTS: On a
      scale of one to five, the mean job autonomy was 3.37, mean perceptions of
      organizational policy was 3.09, and mean safety performance was 3.75.
      Statistically significant positive correlations were found among job autonomy,
      perceptions of organizational policy, and safety performance. Multiple regression
      results found 44% of the variation in safety performance explained by job
      autonomy, length of employment, and perceptions of organizational policy.
      CONCLUSION: Job autonomy and perceptions of organizational policy were positively
      related to safety performance. Hospital executives and nurse managers should work
      to enhance job autonomy and positive perceptions of organizational policy, to
      contribute to improving patient safety.

PMID- 30203436
TI  - The final frontier? Exploring organ transportation by drone.

PMID- 30203437
TI  - Effect of a punctal plug on ocular surface disease in patients using topical
      prostaglandin analogues: A randomized controlled trial - Comment.

PMID- 30203438
TI  - Short chain fatty acids stimulate insulin secretion and reduce apoptosis in mouse
      and human islets in vitro: Role of free fatty acid receptor 2.
AB  - AIMS: To evaluate the role of free fatty acid receptor 2 (FFAR2)/G-protein
      coupled receptor 43 in mediating the effects of the short chain fatty acids
      (SCFAs) sodium acetate (SA) and sodium propionate (SP) on islet function in
      vitro, and to identify the intracellular signalling pathways used in SCFA-induced
      potentiation of glucose-induced insulin secretion. MATERIALS AND METHODS: Islets
      of Langerhans were isolated from wild-type and FFAR2-/- mice and from human
      donors without diabetes. The effects of SA and SP on dynamic insulin secretion
      from perifused islets were quantified by radioimmunoassay, signalling downstream
      of SCFAs was profiled by single-cell calcium microfluorimetry, and measurement of
      cAMP was performed using a fluorescence assay. Islet apoptosis was induced by
      exposure to cytokines or sodium palmitate, and the effects of SA and SP in
      regulating islet apoptosis were assessed by quantification of caspase 3/7
      activities. RESULTS: Deletion of FFAR2 did not affect islet morphology or insulin
      content. SA and SP reversibly potentiated insulin secretion from mouse islets in
      a FFAR2-dependent manner. SCFA-induced potentiation of insulin secretion was
      coupled to Gq activation of phospholipase C and protein kinase C, with no
      evidence of Gi-mediated signalling. SA and SP protected human and mouse islets
      from apoptosis, and these pro-survival properties were dependent on islet
      expression of FFAR2. CONCLUSION: Our results indicate that FFAR2 directly
      mediates both the stimulatory effects of SA and SP on insulin secretion and their
      protection against islet apoptosis. We have also shown that SCFA coupling in
      islets occurs via Gq-coupled intracellular signalling.

PMID- 30203439
TI  - Airway management in microgravity: A systematic review.
AB  - INTRODUCTION: In the near future, space programs will shift their focus toward
      long-duration interplanetary missions, in particular to the Moon and Mars. These
      exploration missions will be associated with an increased risk of acute medical
      problems, which will need to be handled by an autonomous crew operating in
      extreme isolation. An important skill in emergencies is represented by airway
      management. Many airway devices are available and it is unclear which one would
      be the most suitable in the context of a space mission. The aim of this
      systematic review was to analyze the existing literature on airway management in
      the special situation of weightlessness during space missions. MATERIAL AND
      METHODS: We performed a standardized review of published literature on airway
      management in spaceflight and analogue environments using the database PubMed.
      RESULTS: We identified a total of 3111 publications of which 3039 were initially
      excluded after evaluation. The screening identified three randomized comparative
      manikin studies, two of them in parabolic flights, one in a submerged setup.
      Under free-floating conditions, the insertion success rate of supraglottic airway
      devices (SGA) was excellent (91%-97%). The administration of artificial
      ventilation could be successfully achieved in weightlessness with SGA. The
      success rate of conventional laryngoscopy under free-floating conditions
      fluctuated between 15% and 86%. CONCLUSION: It appears possible to safely manage
      the airway in weightlessness, provided that certain conditions are ensured, such
      as restraining the patient and operator for conventional orotracheal intubation.
      If airway protection is required with endotracheal intubation, both the operator
      and the patient should be restrained.

PMID- 30203440
TI  - Haemodynamic stability after paracervical block: A randomized, controlled, double
      blind study comparing bupivacaine-adrenaline with bupivacaine.
AB  - BACKGROUND: Paracervical block is widely used in gynaecological interventions on
      cervix and uterus. Many surgeons add adrenaline 100 MUg or pitressin 3-5 IU in a
      total volume of 10-20 mL to reduce total blood loss. We wanted to examine
      haemodynamic stability in healthy patients given bupivacaine with and without
      adrenaline. METHODS: In this randomised, double-blinded, controlled study, 30
      healthy women scheduled for cervical conisation got a paracervical block using
      bupivacaine 50 mg with adrenaline 100 MUg (BA-group, n = 14) or without
      adrenaline (B-group, n = 16) after induction of general anaesthesia. LiDCOplus
      was used for minimally invasive haemodynamic monitoring. Changes in cardiac
      output (CO) and systolic blood pressure (SBP) were the primary outcome. Changes
      in heart rate (HR), stroke volume (SV), and systemic vascular resistance (SVR)
      were secondary outcome variables. Area under the curve (AUC) ratios and change
      from baseline to maximal values were used as effect measures comparing the two
      groups. RESULTS: The AUC-ratio for CO and SBP was 2.50 (P < 0.001) and 1.70 (P =
      0.03), respectively. For HR, SV, and SVR the AUC-ratio was 1.59 (P < 0.01), 1.52
      (P < 0.001), and 0.90 (P = 0.14), respectively. CO increased 68% (standard
      deviation (SD) 42%, P < 0.001), HR increased 41% (SD 26%, P < 0.001), and SV
      increased 26% (SD 17%, P < 0.001) from baseline to maximal values after 70-90
      seconds in the BA-group. CONCLUSION: Paracervical block with bupivacaine 50 mg
      and adrenaline 100 MUg may give haemodynamic instability in healthy females and
      is not recommended if haemodynamic side effects are to be avoided.

PMID- 30203442
TI  - Glycoproteomics and Glycomics in the Biomedical Area Special Issue.

PMID- 30203441
TI  - Systematic re-evaluation of SCN5A variants associated with Brugada syndrome.
AB  - BACKGROUND: A large number of SCN5A variants have been reported to underlie
      Brugada syndrome (BrS). However, the evidence supporting individual variants is
      highly heterogeneous. OBJECTIVE: We systematically re-evaluated all SCN5A
      variants reported in BrS using the 2015 American college of medical genetics and
      genomics and the association for molecular pathology (ACMG-AMP) guidelines.
      METHODS: A PubMed/Embase search was performed to identify all reported SCN5A
      variants in BrS. Standardized bioinformatic re-analysis (SIFT, PolyPhen, Mutation
      Taster, Mutation assessor, FATHMM, GERP, PhyloP, and SiPhy) and re-evaluation of
      frequency in the gnomAD database were performed. Fourteen ACMG-AMP rules were
      deemed applicable for SCN5A variant analysis. RESULTS: Four hundred and eighty
      unique SCN5A variants were identified, the majority of which 425 (88%) were
      coding variants. One hundred and fifty-six of 425 (37%) variants were classified
      as pathogenic/likely pathogenic. Two hundred and fifty-eight (60%) were
      classified as variants of uncertain significance, while a further 11 (3%) were
      classified as benign/likely benign. When considering the subset of variants that
      were considered "null" variants separately, 95% fulfilled criteria for
      pathogenicity/likely pathogenicity. In contrast, only 17% of missense variants
      fulfilled criteria for pathogenicity/likely pathogenicity. Importantly, however,
      only 25% of missense variants had available functional data, which was a major
      score driver for pathogenic classification. CONCLUSION: Based on contemporary
      ACMG-AMP guidelines, only a minority of SCN5A variants implicated in BrS fulfill
      the criteria for pathogenicity or likely pathogenicity.

PMID- 30203443
TI  - Malayalam speaking Population from South India.
AB  - A total of 356 (217 bone marrow and 139 cord blood donors) Malayalam Speaking
      individuals (Keralites or Malayalis (Here not to be confused with Malayali tribes
      of Eastern ghats from South India)) from Kerala, Tamilnadu, Karnataka and
      Telangana were typed for HLA-A, -B, -C, -DRB and -DQB alleles. Out of 356
      samples, 253 samples were typed by Sanger sequencing using SeCore Sequencing
      IVD(r) kit user protocol (Invitrogen) and the results detected on an automated
      ABI 3730xl DNA analyzer instrument. This article is protected by copyright. All
      rights reserved.

PMID- 30203444
TI  - Nature and scope of synthesis in functional analysis and treatment of problem
      behavior.
AB  - Functional analysis (FA) of problem behavior typically includes the contingent
      delivery of a single reinforcer following problem behavior. However, the FA
      literature also includes examples of analyses that have delivered multiple
      reinforcers, arranged multiple establishing operations in one or more test
      conditions, or both. These analyses have been successfully applied under
      heterogeneous conditions over several decades and with various synthesized
      establishing operations and reinforcers, but their qualitative details, outcomes,
      and contributions to the literature have never been described in a comprehensive
      manner. The purpose of the current review is to: (a) identify articles that have
      reported the use of synthesized FAs or treatments; (b) describe the nature and
      scope of synthesis as it has been applied in the FA literature; (c) analyze
      outcomes of synthesized FAs and treatments to determine general benefits and
      disadvantages of synthesis; and (d) offer recommendations for future areas of
      research.

PMID- 30203445
TI  - Neratinib augments the lethality of [regorafenib + sildenafil].
AB  - Regorafenib is approved for the treatment of colorectal cancer and hepatocellular
      carcinoma. In the trial NCT02466802, we have discovered that regorafenib can be
      safely combined with the phosphodiesterase 5 inhibitor sildenafil in advanced
      solid tumor patients. The present studies determined whether the approved
      ERBB1/2/4 and RAS downregulating drug neratinib, could enhance the lethality of
      [regorafenib + sildenafil]. Neratinib enhanced [regorafenib + sildenafil]
      lethality in a greater than additive fashion in colon cancer cells. The drug
      combination reduced the expression of mutant K-RAS and of multiple histone
      deacetylase (HDAC) proteins that required autophagosome formation. It caused
      green fluorescent protein or red fluorescent protein-tagged forms of K-RAS V12 to
      localize into large intracellular vesicles. Compared with [regorafenib +
      sildenafil], the three-drug combination caused greater and more prolonged
      activation of the ATM-AMPK-ULK-1 pathway and caused a greater suppression and
      prolonged inactivation of mammalian target of rapamycin, AKT, and p70 S6K.
      Approximately 70% of enhanced lethality caused by neratinib required ataxia
      telangiectasia-mutated (ATM)-AMP-dependent protein kinase (AMPK) signaling
      whereas knockdown of Beclin1, ATG5, FADD, and CD95 completely prevented the
      elevated killing effect. Exposure of cells to [regorafenib + sildenafil] reduced
      the expression of the checkpoint immunotherapy biomarkers programmed death-ligand
      1, ornithine decarboxylase, and indoleamine 2,3-dioxygenase-1 and increased the
      expression of major histocompatibility complex A (MHCA), which also required
      autophagosome formation. Knockdown of specific HDAC proteins recapitulated the
      effects observed using chemical agents. In vivo, using mouse cancer models,
      neratinib significantly enhanced the antitumor efficacy of [regorafenib +
      sildenafil]. Our data support performing a new three drug Phase I trial combining
      regorafenib, sildenafil, and neratinib.

PMID- 30203446
TI  - Coupling of Methane and Carbon Dioxide Mediated by Diatomic Copper Boride
      Cations.
AB  - The use of CH4 and CO2 to produce value-added chemicals via direct C-C coupling
      is a challenging chemistry problem because of the inertness of these two
      molecules. Herein, mass spectrometric experiments and high-level quantum-chemical
      calculations have identified the first diatomic species (CuB+ ) that can couple
      CH4 with CO2 under thermal collision conditions to produce ketene (H2 C=C=O), an
      important intermediate in synthetic chemistry. The order to feed the reactants
      (CH4 and CO2 ) is important and CH4 should be firstly fed to produce the C2
      product. Molecular-level mechanisms including control of product selectivity have
      been revealed for coupling of CH4 with CO2 under mild conditions.

PMID- 30203447
TI  - Characterization and cost-benefit analysis of automated bioreactor-expanded
      mesenchymal stem cells for clinical applications.
AB  - BACKGROUND: Expanding quantities of mesenchymal stem cells (MSCs) sufficient to
      treat large numbers of patients in cellular therapy and regenerative medicine
      clinical trials is an ongoing challenge for cell manufacturing facilities. STUDY
      DESIGN AND METHODS: We evaluated options for scaling up large quantities of bone
      marrow-derived MSCs (BM-MSCs) using methods that can be performed in compliance
      with Good Manufacturing Practices (GMP). We expanded BM-MSCs from fresh marrow
      aspirate in alphaMEM supplemented with 5% human platelet lysate using both an
      automated cell expansion system (Quantum, Terumo BCT) and a manual flask-based
      method using multilayer flasks. We compared MSCs expanded using both methods and
      assessed their differentiation to adipogenic and osteogenic tissue, capacity to
      suppress T-cell proliferation, cytokines, and growth factor secretion profile and
      cost-effectiveness of manufacturing enough BM-MSCs to administer a single dose of
      100 * 106 cells per subject in a clinical trial of 100 subjects. RESULTS: We have
      established that large quantities of clinical-grade BM-MSCs manufactured with an
      automated hollow-fiber bioreactor were phenotypically (CD73, CD90, CD105) and
      functionally (adipogenic and osteogenic differentiation and cytokine and growth
      factor secretion) similar to manually expanded BM-MSCs. In addition, MSC
      manufacturing costs significantly less and required less time and effort when
      using the Quantum automated cell expansion system over the manual multilayer
      flasks method. CONCLUSION: MSCs manufactured by an automated bioreactor are
      physically and functionally equivalent to the MSCs manufactured by the manual
      flask method and have met the standards required for clinical application.

PMID- 30203448
TI  - Rheumatoid-nodule-like cutaneous granuloma associated with recombinase activating
      gene 1-deficient severe combined immunodeficiency: A rare case.
AB  - Cutaneous granulomas without detectable infectious etiology rarely occur in
      children and adults with primary immunodeficiency disorders. These cutaneous
      granulomas are primarily seen in combined variable immunodeficiency, ataxia
      telangiectasia, and severe combined immunodeficiency (SCID) and can emulate the
      reaction patterns seen in sarcoidosis and granuloma annulare. To date, the
      literature has described only six cases of non-infectious cutaneous granulomas in
      SCID. We report an unusual case of cutaneous granuloma, mimicking a sarcoma, in a
      40-year old male with recombinase activating gene 1-deficient SCID, who presented
      with a slow-growing globus mass over the lateral aspect of the right elbow. There
      was heterogeneous enhancement on MRI, which was concerning for neoplasm but no
      malignancy was found on frozen or permanent sections. GMS, PAS with diastase, and
      AFB stains, as well as microbiology cultures, were negative. An AE1/AE3 stain was
      negative and a CD163 stain highlighted histiocytes. No infectious etiology was
      identified and histopathology revealed palisaded granulomatous dermatitis, most
      closely resembling a rheumatoid nodule. Although cutaneous manifestations have
      been reported in nearly half of primary immunodeficiency disorder cases, non
      infectious cutaneous granulomas are exceedingly rare in SCID. To our knowledge,
      this is the first case report of cutaneous palisaded granulomatous dermatitis
      mimicking a rheumatoid nodule in a major joint.

PMID- 30203449
TI  - Introduction to Pest Management Science special issue for GHRC 2017.

PMID- 30203451
TI  - Effect of mitochondrial haplogroups on ranibizumab response in neovascular age
      related macular degeneration patients: a pilot study.

PMID- 30203450
TI  - BLACAT1 predicts poor prognosis and serves as oncogenic lncRNA in small-cell lung
      cancer.
AB  - Bladder cancer-associated transcript 1 (BLACAT1) is a novel identified long
      noncoding RNA (lncRNA) in bladder cancer, and has been suggested to function as
      an oncogenic lncRNA in several types of human cancer. However, its involvement in
      the progression of small-cell lung cancer (SCLC) remained unknown. The aim of our
      study was to investigate the clinical value and biological function in SCLC. In
      our results, BLACAT1 expression was increased in SCLC tissues and cell lines
      compared with paired adjacent normal tissues and bronchial epithelial cell lines,
      respectively. In addition, BLACAT1 high-expression was obviously associated with
      advanced clinical stage, large tumor size, more lymph node metastasis, present
      distant metastasis, and poor prognosis. Furthermore, multivariate analysis
      indicated that high-expression of BLACAT1 acted as an independent poor prognostic
      factor for overall survival in SCLC cases. The loss-of-function studies suggested
      that of BLACAT1 suppressed SCLC cell proliferation, migration, and invasion, and
      induced G0/G1 phase arrest. In conclusion, BLACAT1 is associated with the
      malignant status and prognosis in patients with SCLC, and functions as an
      oncogenic lncRNA in regulating cell proliferation and motility, suggesting
      BLACAT1 may act as a potential target for SCLC prevention and treatment.

PMID- 30203452
TI  - Anticoagulation in the cardiac patient: A concise review.
AB  - Anticoagulation has multiple roles in the treatment of cardiovascular disease,
      including in management of acute myocardial infarction, during percutaneous
      coronary intervention, as stroke prophylaxis in patients with atrial arrhythmias,
      and in patients with mechanical heart valves. Clinical anticoagulation choices in
      the aforementioned diseases vary widely, due to conflicting data to support
      established agents and the rapid evolution of evidence-based practice that
      parallels more widespread use of novel oral anticoagulants. This review concisely
      summarizes evidence-based guidelines for anticoagulant use in cardiovascular
      disease, and highlights new data specific to direct oral anticoagulants.

PMID- 30203453
TI  - Actinide-Based Porphyrinic MOF as a Dehydrogenation Catalyst.
AB  - Uranyl-organic frameworks (UOFs) have recently been the object of many research
      endeavors due to the unique coordination mode of uranyl ions and their attractive
      physicochemical properties. Here, a new (3,4)-connected UOF (U-IHEP-4) assembled
      from uranyl and porphyrin ligand tetrakis(4-carboxyphenyl)porphyrin (H4TCPP) is
      reported, which represents the first case of actinide porphyrinic MOFs.
      Adsorption experiments in DMF solution demonstrated that U-IHEP-4 selectively
      adsorbs positively charged dyes, which is in line with its negatively charged
      framework and large pore volume ratio (90 %). Remarkably, U-IHEP-4 exhibited high
      catalytic activity for the dehydrogenation of N-heterocycles to synthesize the
      corresponding aromatic heterocycles and it can be used as an efficient
      heterogeneous catalyst.

PMID- 30203455
TI  - Commentary to the review article: Subedi S, Yu Q, Chen Z, Shi Y. Management of
      pediatric psoriasis with acitretin: A review. Dermatol Ther. 2018 Jan;31(1).

PMID- 30203454
TI  - Social media and its relationship with mood, self-esteem and paranoia in
      psychosis.
AB  - OBJECTIVE: An evidence-base is emerging indicating detrimental and beneficial
      effects of social media. Little is known about the impact of social media use on
      people who experience psychosis. METHOD: Forty-four participants with and without
      psychosis completed 1084 assessments of social media use, perceived social rank,
      mood, self-esteem and paranoia over a 6-day period using an experience sampling
      method (ESM). RESULTS: Social media use predicted low mood, but did not predict
      self-esteem and paranoia. Posting about feelings and venting on social media
      predicted low mood and self-esteem and high paranoia, whilst posting about daily
      activities predicted increases in positive affect and self-esteem and viewing
      social media newsfeeds predicted reductions in negative affect and paranoia.
      Perceptions of low social rank when using social media predicted low mood and
      self-esteem and high paranoia. The impact of social media use did not differ
      between participants with and without psychosis; although, experiencing psychosis
      moderated the relationship between venting and negative affect. Social media use
      frequency was lower in people with psychosis. CONCLUSION: Findings show the
      potential detrimental impact of social media use for people with and without
      psychosis. Despite few between-group differences, overall negative psychological
      consequences highlight the need to consider use in clinical practice.

PMID- 30203456
TI  - A comparative system-level analysis of the neurodegenerative diseases.
AB  - Neurodegenerative diseases are disorders in the central nervous system with
      consequent progressive neurological symptoms including behavioral and cognitive
      disabilities. Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's
      disease, Parkinson's disease, multiple sclerosis, and schizophrenia are the most
      important and abundant neurodegenerative diseases that affect different parts of
      the brain. Detailed studies unveiled the molecular mechanisms and pathways
      affected in each of these disorders. The role of many genes has been documented
      in the onset and progression of each disease. Although many system-level
      approaches have been used to understand the exact cause of these diseases, there
      is no comparative analysis in this regard. Despite all differences in the
      molecular basis of these diseases, overlapping symptoms might indicate the
      involvement of the similar pathways and processes. Here, we have applied a system
      biology approach to uncover many aspects of main neurodegenerative diseases using
      microarray data obtained from 118 cases of postmortem brain samples. Our analysis
      has identified key genes that might contribute to the status of diseases. We have
      also compared the involved biological process and pathway between different
      disease to find possible similar mechanisms that exist in all of them. We also
      predicted potentially important transcription factors in each disease and
      predicted the core gene regulatory networks. We have provided a list of possible
      new key regulators that could be further explored and also discussed the role of
      these hub genes. The results of this study would be useful to develop new
      diagnostic strategies and also to find new drug targets.

PMID- 30203457
TI  - Association between miR-34b/c rs4938723 polymorphism and risk of cancer: An
      updated meta-analysis of 27 case-control studies.
AB  - Several studies investigated the association between miR-34b/c rs4938723
      polymorphism and the risk of several human cancers, but the findings remain
      inconclusive. To evaluate the impact of miR-34b/c rs4938723 on cancer risk, we
      performed a meta-analysis on all available studies including 12 361 cancer cases
      and 14 270 controls. Eligible studies were identified by searching PubMed, Web of
      Science, Scopus, and Google scholar databases. Pooled odds ratios with 95%
      confidence intervals were calculated in codominant, dominant, recessive,
      overdominant, and allele models to quantitatively estimate the association. The
      overall findings showed no significant association between miR-34b/c rs4938723
      polymorphism and cancer risk in codominant, dominant, recessive, overdominant,
      and allele inheritance model. However, in stratified analysis by cancer types,
      the rs4938723 polymorphism significantly increased the risk of gastrointestinal
      cancer, hepatocellular carcinoma. In addition, the rs4938723 polymorphism was
      associated with decreased risk of esophageal squamous cell carcinoma, colorectal
      cancer, and acute lymphoblastic leukemia. The findings did not support an
      association between rs4938723 variant and digestive tract as well as gastric
      cancer. In summary, the findings of this meta-analysis indicated that the miR
      34b/c rs4938723 polymorphism might be associated with some cancer development.
      Larger and well-designed studies are necessary to estimate this association in
      detail.

PMID- 30203458
TI  - In vivo viability of extended 4 degrees C-stored autologous apheresis platelets.
AB  - BACKGROUND: The current 5-day storage time of room temperature (22 degrees C)
      stored platelets (RSPs) severely limits platelet (PLT) availability. Extended
      cold (4 degrees C)-stored PLTs (CSPs) are currently being investigated for
      actively bleeding patients. However, we currently do not know how to best store
      PLTs in the cold for extended periods of time. In this study, we investigate how
      storage in plasma and PLT additive solutions (PASs) affects PLT viability in
      vivo. STUDY DESIGN AND METHODS: Twenty normal subjects had a 2-unit
      hyperconcentrated apheresis PLT collection. One unit was stored at 4 degrees C in
      plasma for 3 days ("control unit"), and the CSP "test" unit was stored for 10 or
      15 days in plasma or 10 days in 35% plasma with either 65% Intersol or Isoplate.
      After storage, all units were radiolabeled and transfused into their donors.
      RESULTS: For 10-day storage, both the plasma and the Intersol units had
      significantly better PLT recoveries than the Isoplate units (24% +/- 8% vs. 11%
      +/- 3% [55% +/- 11% vs. 21% +/- 8% as percentage of control data], p = 0.002; and
      18% +/- 4% vs. 11% +/- 3% [43% +/- 6% vs. 21% +/- 8% as percentage of control
      data], p = 0.004, respectively). There was a trend for lower PLT recoveries with
      Intersol compared to plasma (p = 0.056). PLT survivals and most in vitro
      measurements did not differ significantly among the units. CONCLUSIONS: While the
      in vitro variables suggest largely comparable results between plasma and PASs, in
      vivo recoveries were higher with plasma compared with both Intersol and Isoplate
      (p = 0.057 and p = 0.002, respectively). Whether this difference leads to
      clinically relevant differences in hemostatic efficacy remains to be determined.

PMID- 30203459
TI  - Multimodal imaging to explore endogenous fluorescence of fresh and fixed human
      healthy and tumor brain tissues.
AB  - To complement a project toward label-free optical biopsy and enhanced resection
      which the overall goal is to develop a multimodal nonlinear endomicroscope, this
      multimodal approach aims to enhance the accuracy in classifying brain tissue into
      solid tumor, infiltration and normal tissue intraoperatively. Multiple optical
      measurements based on one- and two-photon spectral and lifetime autofluorescence,
      including second harmonic generation imaging, were acquired. As a prerequisite,
      studying the effect of the time of measurement postexcision on tissue's
      spectral/lifetime fluorescence properties was warranted, so spectral and lifetime
      fluorescences of fresh brain tissues were measured using a point-based linear
      endoscope. Additionally, a comparative study on tissue's optical properties
      obtained by multimodal nonlinear optical imaging microscope from fresh and fixed
      tissue was necessary to test whether clinical validation of the nonlinear
      endomicroscope is feasible by extracting optical signatures from fixed tissue
      rather than from freshly excised samples. The former is generally chosen for
      convenience. Results of this study suggest that an hour is necessary postexcision
      to have consistent fluorescence intensities?lifetimes. The fresh (a,b,c) vs fixed
      (d,e,f) tissue study indicates that while all optical signals differ after
      fixation. The characteristic features extracted from one- and two-photon
      excitation still discriminate normal brain (a,d) cortical tissue, glioblastoma
      (GBM) (b,e) and metastases (c,f).

PMID- 30203460
TI  - Supervisory relationships in long-term care facilities: A comparative case study
      of two facilities using complexity science.
AB  - AIMS: This study aims to understand the factors that contribute to supervisory
      nurse performance in long-term care facilities. BACKGROUND: Long-term care
      facilities have been faced with staffing challenges and increasing resident care
      needs, resulting in suboptimal quality of care. Nursing leadership has been
      identified as a key factor in the provision of high-quality care. METHODS: The
      comparative case study employed a complexity science framework to compare two
      facilities. The facilities were chosen based on the level of perceived
      supervisory support staff received from their supervisors, and 10 participants
      were recruited from each facility at various levels of management and staff (n =
      20). Data were collected in 2015 using semi-structured interviews. FINDINGS: The
      quality and quantity of supervisory relationships was central to shaping the
      effectiveness of the supervision. Effective supervisory support was characterized
      by frequent and high-quality supervisor-staff interactions. Effective nurse
      supervisors acknowledged self-organisation as beneficial, and worked in
      environments that encouraged fluidity of roles. CONCLUSIONS: The findings suggest
      that effective nurse supervisors and supervisory support fosters improved work
      environments and the staff's ability to respond to residents' needs in a timely,
      effective and compassionate manner. IMPLICATIONS FOR NURSING MANAGEMENT: Nurse
      managers who provide effective supervisory support can improve the quality of
      care provided to their residents.

PMID- 30203461
TI  - Association between the -11377 C/G and -11391 G/A polymorphisms of adiponectin
      gene and adiponectin levels with susceptibility to type 1 and type 2 diabetes
      mellitus in population from the west of Iran, correlation with lipid profile.
AB  - Adipose tissue, an endocrine organ, secretes bioactive factors including
      adiponectin. Adiponectin is a protein hormone that enhances insulin sensitivity
      through increased fatty acid oxidation and inhibition of hepatic glucose
      production. We assessed the association of the adiponectin promoter region
      polymorphisms -11391 G/A and -11377 C/G with susceptibility to type 1 (T1DM) and
      type 2 (T2DM) diabetes mellitus in the population of west Iran. Also, we
      investigated the effect of adiponectin level and lipid profile on T1DM and T2DM
      development. In this case-control study, we recruited 189 patients with diabetes
      (100 T2DM and 89 T1DM) and 161 sex and age-matched unrelated healthy controls.
      Adiponectin mutations were detected by polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP), and the protein level was measured by
      the enzyme-linked immunosorbent assay. Other biochemical parameters were
      determined by routine laboratory methods. The G allele of adiponectin gene at 
      11377 position (C/G) significantly increased the risk of T1DM. With respect to
      genotype models, codominant (2.97 times), dominant (3.6-fold), and over
      codominant (2.9-fold) patients with T1DM who carried -11377 C > G single
      nucleotide polymorphisms were significantly susceptible to the development of the
      disease. A significantly higher level of adiponectin in T1DM was oberved compared
      with the control group. In contrast, patients with T2DM had lower adiponectin
      levels compared with healthy controls. The genotype distributions of -11391 G/A
      polymorphisms were the same for patients with diabetes and control groups. The
      presence of G allele at -11377 C/G adiponectin gene significantly increased serum
      adiponectin level and may be a risk factor for T1DM susceptibility among the
      western Iranian population.

PMID- 30203463
TI  - The consistency of circadian blood pressure and heart rate patterns over three
      months in women employed in sedentary office jobs.
AB  - OBJECTIVES: The purpose of this study was to evaluate the consistency of the
      circadian patterns of blood pressure (BP) and heart rate (HR) variation over a
      three-month time frame in women employed outside the home. METHODS: The subjects
      were 157 healthy women of varying ethnicity (age = 38.2 +/- 8.9) who all worked
      in similar positions at two major medical centers in New York City. Each wore an
      ambulatory BP monitor during the course of three mid-week work days approximately
      one month apart. Hourly BPs and HRs were calculated from 9 am to 6 am the
      following morning and compared among the three days using anova and t tests.
      RESULTS: The results indicate that there were virtually no differences in the
      mean hourly levels of any parameter during the waking period across the three
      days of assessment. However, mean hourly levels of systolic BP significantly
      declined from 12 pm to 4 am (P < .04, P = .001, P < .001, P = .001, P = .009,
      respectively) on the third assessment day compared to the first. CONCLUSIONS:
      Because BP and HR respond to environmental demands in an allostatic fashion, the
      consistency in the waking patterns of BP and HR variation suggest that the
      patterns of demands on a workday are reasonably stable in this sample of women.
      The decline in systolic pressures from 12 pm to 4 am over the three assessments
      may indicate an improving ability to sleep with the monitor over time.

PMID- 30203462
TI  - Acute metabolic and cardiovascular effects of mirabegron in healthy individuals.
AB  - AIMS: To quantify acute energy expenditure, supraclavicular skin temperature and
      cardiovascular responses to four doses of the beta3-adrenoceptor agonist,
      mirabegron. MATERIALS AND METHODS: A total of 17 individuals (11 men, six women)
      participated in this ascending-dose study, receiving single 50-, 100-, 150- and
      200-mg doses of mirabegron on four separate days with 3 to 14 days wash-out
      between each dose. All variables were measured each visit from baseline to 180
      minutes post mirabegron treatment. To determine brown adipose tissue (BAT)
      thermogenic efficacy at each dose, energy expenditure and supraclavicular skin
      temperature were compared from baseline to 180 minutes post mirabegron treatment.
      To examine safety, changes in cardiovascular variables at 100, 150 and 200 mg
      were compared with the standard clinical dose of 50 mg. RESULTS: Energy
      expenditure significantly increased after the 100- (35.6 +/- 5.4 kJ/h) and 200-mg
      (35.6 +/- 13.1 kJ/h) doses (P <= 0.05), and trended towards an increase after 150
      mg (24.1 +/- 13.6 kJ/h). Supraclavicular skin temperature increased after 50-
      (0.22 +/- 0.1 degrees C), 100- (0.30 +/- 0.1 degrees C) and 150-mg mirabegron
      doses (0.29 +/- 0.1 degrees C; P <= 0.05). The change in systolic blood pressure
      was greater after 150- (7.1 +/- 1.3 mm Hg) and 200-mg doses (9.3 +/- 1.9 mm Hg)
      than after the 50-mg dose (2.2 +/- 1.3 mm Hg; P <= 0.05). The change in heart
      rate was greater after 200 mg (9.0 +/- 2.2 bpm) compared with 50 mg (2.9 +/- 1.4
      bpm; P <= 0.05). CONCLUSIONS: A 100-mg dose of mirabegron increases energy
      expenditure and supraclavicular skin temperature in a beta3-adrenoceptor-specific
      manner, without the off-target elevations in blood pressure or heart rate
      observed at higher doses.

PMID- 30203464
TI  - Effect of time pressure on the burnout of home-visiting nurses: The moderating
      role of relational coordination with nursing managers.
AB  - AIM: To examine the main effects of time pressure and relational coordination
      with nursing managers on burnout and to further analyze the moderating role of
      relational coordination with nursing managers on the association between time
      pressure and burnout among home-visiting nurses in Japan. METHODS: This was a
      cross-sectional, quantitative study comprising 93 home-visiting nurses in Japan.
      A hierarchical moderated regression analysis with mean-centered predictor
      variables was used to explore the main effects of time pressure and relational
      coordination with nursing managers on burnout and the moderating effect of
      relational coordination with nursing managers on the time pressure and burnout
      relationship. RESULTS: Time pressure was a significant positive predictor for
      emotional exhaustion and depersonalization, respectively. Relational coordination
      with the nursing managers was significantly and negatively related to
      depersonalization; however, its main effect on exhaustion was non-significant.
      Significant interaction effects of time pressure and relational coordination with
      the nursing managers on exhaustion and depersonalization also were identified.
      Time pressure was a significant positive contributor to exhaustion and
      depersonalization when the home-visiting nurses reported low relational
      coordination with the nursing managers. CONCLUSION: Relational coordination with
      nursing managers is a critical resource for dealing with high time pressure.
      Strategies, such as establishing a skill-mix program to alleviate nurses' time
      pressure and creating a supportive work environment to facilitate relational
      coordination with nursing managers, might be effective ways to prevent burnout,
      as well as management interventions among home-visiting nurses.

PMID- 30203465
TI  - Replicating measurements of total hemoglobin mass (tHb-mass) within a single day:
      precision of measurement; feasibility and safety of using oxygen to expedite
      carbon monoxide clearance.
AB  - Hemoglobin concentration ([Hb]) is a function of total hemoglobin mass (tHb-mass)
      and plasma volume. [Hb] may fall by dilution due to plasma volume expansion and
      changes in the perioperative period may therefore correlate poorly with blood
      loss. A simple, reliable, repeatable way to measure plasma volume and tHb-mass
      would have substantial clinical utility. The "optimized carbon monoxide re
      breathing method" (oCOR) meets these criteria. However, it is recommended that a
      minimum of 12 h (when breathing room air) is left between repeat measurements.
      Twenty-four subjects underwent 3 days of testing. Two oCOR tests were performed
      (T1 and T2), 3 h apart, with a different CO clearance method employed between
      tests aiming to keep the carboxyhemoglobin level below 10%. The primary aim was
      to ascertain whether tHb-mass testing could be safely repeated within 3 h if
      carboxyhemoglobin levels were actively reduced by breathing supplemental oxygen
      (PROCA ). Secondary aims were to compare two other clearance methods; moderate
      exercise (PROCB ), or a combination of the two (PROCC ). Finally, the reliability
      of the oCOR method was assessed. Mean (SD) tHb-mass was 807.9 +/- (189.7 g) (for
      T1 on day 1). PROCA lowered the carboxyhemoglobin level from the end of T1 (mean
      6.64%) to the start of T2 (mean 2.95%) by a mean absolute value of 3.69%. For
      PROCB and PROCC the mean absolute decreases in carboxyhemoglobin were 4.00% and
      4.31%, respectively. The fall in carboxyhemoglobin between T1 and T2 was greatest
      in PROCC ; this was statistically significantly lower than that of PROCA (P =
      0.0039) and PROCB (P = 0.0289). The test-retest reliability for the measurement
      of total hemoglobin mass was good with a mean typical error (TE) of 2.0%. The
      oCOR method is safe and can be repeated within 3 h when carbon monoxide is
      suitably cleared between tests. Using oxygen therapy alone adequately achieves
      this.

PMID- 30203466
TI  - Evaluation of systemic microvascular reactivity in adults with congenital heart
      disease.
AB  - OBJECTIVE: Adults with congenital heart disease share some features with those
      with chronic heart failure. Although microvascular endothelial dysfunction has
      been described in chronic heart failure, evaluation of the microcirculation in
      adults with congenital heart disease is lacking. The present study aimed to
      investigate systemic microvascular reactivity in adults with congenital heart
      disease. INTERVENTIONS: The patients initially underwent cardiopulmonary exercise
      testing. Then, the cutaneous microvascular reactivity was evaluated in these
      patients using a laser speckle contrast imaging system coupled with skin
      iontophoresis of endothelial-dependent (acetylcholine) or -independent (sodium
      nitroprusside) vasodilators and postocclusive reactive hyperemia (PORH) and
      compared with healthy controls matched for age and sex. RESULTS: Thirty-one
      patients and 29 healthy controls were evaluated. The basal microvascular flow (P
      < .0001) and area under the curve in response to acetylcholine (P < .0001) were
      higher in the patients than in the healthy volunteers. The increase in cutaneous
      vascular conductance in response to sodium nitroprusside was reduced in the
      patients compared to the healthy volunteers (P = .0031). No difference in the
      microvascular response was observed during postocclusive reactive hyperemia. The
      basal microvascular flow of patients with peak oxygen consumption below 16.0 mL
      kg-1 min-1 was superior to that of patients with values greater than 16.0 mL kg-1
      min-1 (P = .0046). CONCLUSIONS: Adults with congenital heart disease present a
      higher baseline cutaneous microvascular blood flow than healthy controls and do
      not present systemic microvascular endothelial dysfunction. Nevertheless,
      endothelium-independent microvascular reactivity is blunted, suggesting an
      altered vascular smooth muscle response or vascular structural alterations.
      Finally, patients with a lower functional capacity presented a greater
      microvascular basal blood flow than subjects with a higher functional capacity.

PMID- 30203467
TI  - Power and sample size for dose-finding studies with survival endpoints under
      model uncertainty.
AB  - Multiple comparison procedures combined with modeling techniques (MCP-Mod) (Bretz
      et al., ) is an efficient and robust statistical methodology for the model-based
      design and analysis of dose-finding studies with an unknown dose-response model.
      With this approach, multiple comparison methods are used to identify
      statistically significant contrasts corresponding to a set of candidate dose
      response models, and the best model is then used to estimate the target dose.
      Power and sample size calculations for this methodology require knowledge of the
      covariance matrix for the estimators of the (placebo-adjusted) mean responses
      among the dose groups. In this article, we consider survival endpoints and derive
      an analytic form of the covariance matrix for the estimators of the log hazard
      ratios as a function of the total number of events in the study. We then use this
      closed-form expression of the covariance matrix to derive the power and sample
      size formulas. We discuss practical considerations in the application of these
      formulas. In addition, we provide an illustration with a motivating example on
      chronic obstructive pulmonary disease. Finally, we demonstrate through simulation
      studies that the proposed formulas are accurate enough for practical use.

PMID- 30203468
TI  - Acute kidney injury after burn surgery: Preoperative neutrophil/lymphocyte ratio
      as a predictive factor.
AB  - BACKGROUND: Severe inflammation and acute kidney injury (AKI) are serious adverse
      events after burn injuries. The neutrophil/lymphocyte ratio (NLR) is a marker of
      inflammation. We evaluated the independent risk factors for postoperative AKI,
      including NLR, in burn-injured patients. METHODS: The preoperative,
      intraoperative, and postoperative variables of 473 burn-injured patients were
      collected. The risk factors for AKI after burn surgery were evaluated using
      univariate and multivariate logistic regression analyses. The receiver operating
      characteristic (ROC) curve analysis of preoperative NLR was performed. The 3
      month mortality after surgery was also compared between AKI and non-AKI groups
      using Kaplan-Meier analysis with a log-rank test. RESULTS: Postoperative AKI
      occurred in 71 of 473 (15.0%) burn patients. The total body surface area burned
      (odds ratio (OR), 1.013; 95% confidence interval (CI), 1.001-1.026; P = 0.037),
      inhalation injury (OR, 1.821; 95% CI, 1.008-3.292; P = 0.047), and preoperative
      NLR (OR, 1.094; 95% CI, 1.064-1.125; P < 0.001) were risk factors for AKI after
      surgery. The area under the ROC curve was 0.767, with an optimal cut-off value of
      11.7. Moreover, the 3-month mortality after surgery was significantly higher in
      the AKI group than in the non-AKI group (49.3% vs 14.9%, P < 0.001). CONCLUSION:
      Total body surface area burned, inhalation injury, and preoperative NLR are risk
      factors for AKI after burn surgery, which is associated with early postoperative
      mortality. Preoperative NLR can provide useful information for the early
      detection of postoperative AKI and subsequent mortality in burn-injured patients.

PMID- 30203469
TI  - Selective motor control and gross motor function in bilateral spastic cerebral
      palsy.
AB  - AIM: To investigate the relationship between selective motor control (SMC),
      muscle volume, and spasticity with gross motor function in adolescents and young
      adults with bilateral spastic cerebral palsy (CP). METHOD: Eleven male
      participants with CP (mean age 15y 7mo, standard deviation 3y 6mo, range 12y 1mo
      23y 1mo) in Gross Motor Function Classification System (GMFCS) levels I to IV
      took part in this cross-sectional study. Magnetic resonance imaging (MRI) of both
      lower limbs of all participants were acquired, from which 18 muscles were
      manually segmented and muscle volume calculated by a single assessor. Muscle
      volumes were normalized to body mass and averaged between limbs for each
      individual. SMC was assessed using Selective Control Assessment of the Lower
      Extremity (SCALE). Spasticity was assessed using the Modified Ashworth Scale
      (MAS), and gross motor functional ability was assessed using the Gross Motor
      Function Measure (GMFM-66). RESULTS: GMFM-66 was strongly positively correlated
      to SCALE (r=0.901, p<=0.001) and lower limb muscle volume normalized to body mass
      (r=0.750, p=0.008). MAS was significantly correlated with GMFM-66 (r=-0.691,
      p=0.018). INTERPRETATION: SMC is a major factor influencing gross motor function
      in individuals with CP. Lower limb muscle volume and spasticity also influence
      gross motor function. WHAT THIS PAPER ADDS: Selective motor control is a major
      factor of gross motor function in adolescents and young adults with bilateral
      cerebral palsy (CP). Gross motor function is related to muscle size and level of
      spasticity in adolescents and young adults with bilateral CP.

PMID- 30203470
TI  - Description of a new Pimelodella (Siluriformes: Heptapteridae) species with a
      discussion on the upper pectoral girdle homology of Siluriformes.
AB  - A new species of Pimelodella is described from several right-bank tributaries of
      the Rio Madeira basin in Amazonas and Rondonia states, Brazil. The new species
      differs from all congeners by the supraoccipital process not reaching the
      anterior nuchal plate, 43-45 total vertebrae, maxillary barbels reaching between
      adpressed anal-fin terminus and caudal-fin origin, epiphyseal branch of
      supraorbital laterosensory canal emerging as two distantly-positioned pores and a
      conspicuous black mark at distal third of dorsal fin, between dorsal-fin spine
      and third branched ray. A detailed description of the cephalic laterosensory
      system of the new species is provided and contrasted with other Siluriformes and
      Ostariophysi. A discussion regarding homology of the catfish upper pectoral
      girdle bones is offered in light of modifications of the postotic and
      supratemporal lateral-line canals. Based on the placement of the pterotic branch
      of the postotic canal, it is concluded that the extrascapula is fused to the
      pterotic in Siluriformes. Results presented herein offer an example of how
      lateral-line morphology can be used as a compelling source of evidence to help
      determine homology of cranial and upper pectoral girdle bones.

PMID- 30203471
TI  - Liposomal nanocarriers for statins: A pharmacokinetic and pharmacodynamics
      appraisal.
AB  - Statins, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, are a
      well-known class of drug with beneficial therapeutic effects in cardiovascular
      disease and lipid disorders and have potential use against cancer. However, the
      bioavailability of statins is hampered due to low aqueous solubility and rapid
      metabolism. To improve pharmacokinetic profiles of statins, development of drug
      delivery systems is promising. Hence, the use of liposomes for selective delivery
      of statins to a selected site or for bioavailability enhancement is an effective
      strategy to increase statin therapeutic effects. Moreover, liposomal delivery can
      reduce the required dose of statins especially in terms of antitumor effects.
      Liposomes, because of their unique properties and biphasic and amphiphilic
      nature, have attracted much interest and can be considered as a suitable choice
      for delivery of both hydrophilic and lipophilic statins. In this review article,
      we focus on liposomes and evaluate the effects of different liposomal delivery
      systems, based on differences in size, phospholipid composition, circulation half
      life, and cholesterol content, on statin function.

PMID- 30203472
TI  - Bias and sample size in intensive care unit trials: Protocol for a meta
      epidemiological study.
AB  - BACKGROUND: Systematic errors (bias) and random errors result in inflated and
      imprecise intervention effect estimates in randomised clinical trials (RCT) and
      meta-analyses. We aim to assess time trends in the Cochrane risk of bias domains
      and sample size in RCTs of intensive care unit (ICU) interventions. METHODS AND
      DESIGN: We will conduct a meta-epidemiologic study of RCTs included in Cochrane
      systematic reviews assessing any intervention used in adult patients admitted to
      the ICU. We will search the Cochrane Database of Systematic Reviews and include
      reviews published from March 2011 corresponding to the latest update in the
      Cochrane risk of bias tool. We will extract data on risk of bias judgments in the
      seven Cochrane bias domains and trial sample sizes and evaluate time trends using
      run charts. The primary outcome will be time trends in the annual proportion of
      trials with overall low risk of bias (low risk of bias in all bias domains). The
      secondary outcomes include time trends in the annual median trial sample size,
      and the annual proportion of trials with low-, unclear- and high risk of bias in
      each of the seven Cochrane bias domains. DISCUSSION: The outlined meta
      epidemiologic study will assess time trends in risk of bias and sample sizes in
      RCTs assessing ICU interventions. This will inform researchers, healthcare
      personnel and policymakers on the general reliability of findings from RCTs of
      ICU interventions over time, and inform future RCT design and reporting.

PMID- 30203473
TI  - Diagnostic Accuracy of Dysphonia Classification of DSI and AVQI.
AB  - OBJECTIVE: The Dysphonia Severity Index (DSI) and the Acoustic Voice Quality
      Index (AVQI) have been successfully investigated to quantify voice quality. The
      aim of the present study was to evaluate the diagnostic accuracy of both
      measurements in comparison with the dysphonia classification. METHODS: In total,
      264 subjects with vocally healthy voices (n = 105) and with various voice
      disorders (n = 159) were included in the study. To determine the dysphonia
      classification, all subjects underwent a videolaryngostroboscopy and, if
      necessary, a direct microlaryngoscopy plus a clinical examination to diagnose a
      voice disorder. Patients with a vocally healthy voice had no actual voice
      complaints, no history of chronic laryngeal diseases or voice disorders, no
      hearing problems and were determined as healthy voices by clinical voice
      specialists. To evaluate the diagnostic accuracy, receiver operating
      characteristic statistics and correct classification rate (CCR) were used.
      RESULTS: The diagnostic accuracy of DSI and AVQI showed strong sensitivity and
      specificity in the determination of dysphonia classification. A DSI threshold of
      3.05 obtained a high sensitivity of 94.3% and specificity of 84.3%. An CCR of 88%
      was determined for DSI. Also, an AVQI threshold of 3.31 showed reasonable
      sensitivity of 71.7% and specificity of 88%. The CCR for AVQI was 79%.
      CONCLUSION: Although DSI and AVQI were developed to quantify voice quality, the
      present results showed that both measurements can evaluate the dysphonia
      classification as well. Particularly, the DSI might have higher potential in the
      evaluation of dysphonia classification. LEVEL OF EVIDENCE: 2c. Laryngoscope,
      2018.

PMID- 30203475
TI  - Far-red light enhances photochemical efficiency in a wavelength-dependent manner.
AB  - Linear electron transport depends on balanced excitation of photosystem I and II.
      Far-red light preferentially excites photosystem I (PSI) and can enhance the
      photosynthetic efficiency when combined with light that over-excites photosystem
      II (PSII). The efficiency of different wavelengths of far-red light exciting PSI
      was quantified by measuring the change in quantum yield of PSII (PhiPSII ) of
      lettuce (Lactuca sativa) under red/blue light with narrowband far-red light added
      (from 678 to 752 nm, obtained using laser diodes). The PhiPSII of lettuce
      increased with increasing wavelengths of added light from 678 to 703 nm,
      indicating longer wavelengths within this region are increasingly used more
      efficiently by PSI than by PSII. Adding 721 nm light resulted in similar PhiPSII
      as adding 703 nm light, but PhiPSII tended to decrease as wavelength increased
      from 721 to 731 nm, likely due to decreasing absorptance and low photon energy.
      Adding 752 nm light did not affect PhiPSII . Leaf chlorophyll fluorescence light
      response measurements showed lettuce had higher PhiPSII under halogen light (rich
      in far-red) than under red/blue light (which over-excites PSII). Far-red light is
      more photosynthetically active than commonly believed, because of its synergistic
      interaction with light of shorter wavelengths.

PMID- 30203474
TI  - Introduction of a pseudo demons force to enhance deformation range for robust
      reconstruction of super-resolution time-resolved 4DMRI.
AB  - PURPOSE: The purpose of this study was to enhance the deformation range of demons
      based deformable image registration (DIR) for large respiration-induced organ
      motion in the reconstruction of time-resolved four-dimensional magnetic resonance
      imaging (TR-4DMRI) for multi-breath motion simulation. METHODS: A demons-based
      DIR algorithm was modified to enhance the deformation range for TR-4DMRI
      reconstruction using the super-resolution approach. A pseudo demons force was
      introduced to accelerate the coarse deformation in a multi-resolution (n = 3) DIR
      approach. The intensity gradient of a voxel was applied to its neighboring (5 * 5
      * 5) voxels with a weight of Gaussian probability profile (sigma = 1 voxel) to
      extend the demons force, especially on those voxels that have little intensity
      gradience but high-intensity difference. A digital 4DMRI phantom with 3-8 cm
      diaphragmatic motions was used for DIR comparison. Six volunteers were scanned
      with two high-resolution (highR: 2 * 2 * 2 mm3 ) breath-hold (BH) 3DMR images at
      full inhalation (BHI) and full exhalation (BHE) and low-resolution (lowR: 5 * 5 *
      5 mm3 ) free-breathing (FB) 3DMR cine images (2 Hz) under an IRB-approved
      protocol. A cross-consistency check (CCC) (BHI->FB<-BHE), with voxel intensity
      correlation (VIC) and inverse consistency error (ICE), was introduced for cross
      verification of TR-4DMRI reconstruction. RESULTS: Using the digital phantom, the
      maximum deformable magnitude is doubled using the modified DIR from 3 to 6 cm at
      the diaphragm. In six human subjects, the first 15-iteration DIR using the pseudo
      force deforms 200 +/- 150% more than the original force, and succeeds in all 12
      cases, whereas the original demons-based DIR failed in 67% of tested cases. Using
      the pseudo force, high VIC (>0.9) and small ICE (1.6 +/- 0.6 mm) values are
      observed for DIR of BHI&BHE, BHI->FB, and BHE->FB. The CCC identifies four
      questionable cases, in which two cases need further DIR refinement, without
      missing true negative. CONCLUSIONS: The introduction of a pseudo demons force
      enhances the largest deformation magnitude up to 6 cm. The cross-consistency
      check ensures the quality of TR-4DMRI reconstruction. Further investigation is
      ongoing to fully characterize TR-4DMRI for potential multi-breathing-cycle
      radiotherapy simulation.

PMID- 30203477
TI  - Active Commuting to School, Physical Activity, and Behavior Problems Among Third
      Grade Children.
AB  - BACKGROUND: We examined factors associated with active commuting to school and
      the relationships of active commuting and physical activity to child- and teacher
      reported internalizing and externalizing behavior problems in a sample of third
      graders. METHODS: The study sample consisted of 13,166 third graders enrolled in
      the Early Childhood Longitudinal Study Kindergarten Class of 1998-1999. "Active"
      commuters were children who walked to school and "passive" commuters were those
      who took the bus or were driven. Linear analyses evaluated differences in
      behavior problems by school commute, physical activity, and sports team
      participation after adjusting for sociodemographic, regional, and neighborhood
      factors. RESULTS: Overall, 11% of children actively commuted. Type of commute
      differed by sociodemographics, region, urbanicity, school type, and neighborhood
      safety. Active commuters had less general physical activity participation and
      sports team participation. Commuting type and general physical activity were not
      associated with behavior problems, but sports team participation was associated
      with fewer child-reported internalizing and externalizing behaviors as well as
      fewer teacher-reported internalizing behaviors. CONCLUSIONS: Our findings
      demonstrate the ongoing need for creating and maintaining physical activity
      programs (such as sports teams) among school-aged children to optimize children's
      overall health and well-being.

PMID- 30203476
TI  - The Effects of Asthma and Bullying on Suicidal Behaviors Among US Adolescents.
AB  - BACKGROUND: Positive associations between suicidal behaviors and asthma have been
      established in previous adolescent studies. Few studies consider social risk
      factors, such as bullying. This study involved an analysis of suicidal behaviors
      and asthma, but also includes an assessment of whether these relationships were
      modified by the co-occurrence of bullying. METHODS: Data included 13,154
      participants from the 2013 Youth Risk Behavior Survey (YRBS), collected by the US
      Centers for Disease Control and Prevention. Logistic regression models were
      constructed and summarized using odds ratios (ORs) and 95% confidence intervals
      (95% CIs). RESULTS: When comparing adolescents with asthma who were bullied at
      school to those who were not bullied at school, the odds of contemplating suicide
      were increased by nearly 2-fold (OR = 1.8, 95% CI = 1.5-2.3), and the odds of
      creating a suicide plan were 2.3 times higher (OR = 2.3, 95% CI = 1.7-3.1). The
      odds of a suicide attempt and incurring an injury from a suicide attempt were
      also substantially increased. Similarly, increased odds of suicidal behaviors
      were observed for adolescents with asthma who were bullied electronically.
      CONCLUSION: Having asthma and being bullied are both associated with increased
      odds of suicidal behaviors.

PMID- 30203478
TI  - Composition of School Meals in Sweden, Finland, and Iceland: Official Guidelines
      and Comparison With Practice and Availability.
AB  - BACKGROUND: Nutritious and attractive school meals can improve health equality
      and public health. Current official guidelines and recommendations on food and
      nutrient composition of school meals in 3 Nordic countries; Sweden, Finland, and
      Iceland, are described and compared with actual practice, ie, availability of
      foods and nutrients in served reference meals in 3 selected areas in each
      country. METHODS: A country comparison was made between official guidelines, and
      actual practice was studied in participating schools. Reference portions of
      school meals (N = 170) provided in 24 compulsory schools were photographed and
      weighed. Food and nutrient availability were compared with official guidelines in
      each country. RESULTS: Emphasis of recommendations on whole-grain bread in
      Sweden, whole grains in Finland, and fish in Iceland were reflected in food
      availability. The energy content of the meals provided was lower than guidelines
      and there was a large variation in energy content between days. CONCLUSIONS: The
      guidelines regarding food availability were quite well followed, but the large
      variation in energy and nutrient content of provided school meals between days
      indicates a need for standardization.

PMID- 30203479
TI  - Effects of a School-Based Pedometer Intervention in Adolescents: 1-Year Follow-Up
      of a Cluster-Randomized Controlled Trial.
AB  - BACKGROUND: Physical activity (PA) is one of the most important health behaviors
      that may be modified by each individual. To foster PA in adolescents, a school
      based intervention was evaluated. METHODS: A cluster-randomized controlled trial
      with preassessment in 2014 and follow-up assessment in 2015 included 29 schools
      with 1020 students (47.6% girls, mean age = 13.69 years). Intervention students
      received pedometers and monitored their steps for 12 weeks. Classes with the most
      steps were awarded. Primary outcomes included moderate-to-vigorous PA, out-of
      school sports activities, active transport assessed through questionnaires, as
      well as cardiorespiratory fitness measured using the 20-m shuttle-run test and
      anthropometric data (weight, height, body fat, and waist circumference) assessed
      by study staff. RESULTS: Significant interaction terms between group and time
      were found for all 3 indicators of PA; intervention students showed a higher
      increase of PA than control students. The same pattern was shown for
      cardiorespiratory fitness, but the effect missed significance. A more favorable
      development for the intervention students was shown for body fat and waist-to
      height ratio, while there was no effect on body mass index percentile.
      CONCLUSIONS: An easy way to administer school-based PA program may enhance
      students' leisure-time PA even 1 year after the intervention has ended.

PMID- 30203480
TI  - Perceived Weight Discrimination and School Connectedness Among Youth: Does
      Teacher Support Play a Protective Role?
AB  - BACKGROUND: Weight discrimination has been associated with poor academic
      performance and decreased school attendance. Little is known about weight
      discrimination and students' feelings of belonging to their school. This study
      examined the association between weight discrimination and school connectedness
      among adolescents. Teacher support was examined as a protective factor. METHODS:
      Middle school students (N = 639; 57% white; Mean age = 12.16 years) completed a
      health behaviors survey. Weight discrimination from peers and/or good friends was
      dichotomized into never versus experienced weight discrimination. The mean of 5
      school connectedness items assessed level of school connectedness. Teacher
      support was measured by taking the mean of 4 teacher support items. Hierarchical
      linear regression was used to examine the association between weight
      discrimination and school connectedness. Teacher support was tested as a
      moderator. RESULTS: Weight discrimination was associated with lower levels of
      school connectedness (p < .05). Teacher support was associated with higher levels
      of school connectedness (p < .001) but did not moderate the association between
      weight discrimination and school connectedness. CONCLUSION: The association
      between weight discrimination and low levels of school connectedness is important
      as students spend most of their time at school and should benefit from the
      positive effects of feeling connected to school.

PMID- 30203481
TI  - Effects of a Collaborative Board Game on Bullying Intervention: A Group
      Randomized Controlled Trial.
AB  - BACKGROUND: We examined the effects of the Galaxy Rescuers game, a collaborative
      board game on schoolchildren's bullying intervention. METHODS: We conducted a
      group-randomized controlled trial. We recruited 328 fifth graders at an
      elementary school in northern Taiwan. The study took place in fall 2015 over a 7
      week period. We used the generalized estimation equation (GEE) to evaluate the
      intervention effects on students' scores on the outcome measures. RESULTS: At
      posttest, the change in bullying knowledge was statistically significant for the
      game-only group and the game-with-debriefing group. Students in the game-with
      debriefing group also showed an increase in empathy and a decrease in bullying
      attitude. At the follow-up test, knowledge increase remained significant for both
      the game-only group and the game-with-debriefing group. Game satisfaction survey
      indicated that 66.8% of the players said that the game was enjoyable.
      CONCLUSIONS: The Galaxy Rescuers game is effective in changing players' bullying
      knowledge, attitude, and empathy. This game is an entertaining tool for promoting
      awareness of bullying and encouraging defending atmosphere among children.

PMID- 30203483
TI  - National Analysis of State Health Policies on Students' Right to Self-Carry and
      Self-Administer Asthma Inhalers at School.
AB  - BACKGROUND: Asthma has no known cure, and though manageable, it disrupts the
      everyday lives of over 6 million US children. Because children spend more than
      half of their waking hours in school, students must be able to carry and
      administer their inhaler at school to manage their asthma. METHODS: This policy
      paper is a comprehensive review of all 50 states and the District of Columbia's
      laws and policies for the self-carry and administration of quick-relief asthma
      inhalers among children in prekindergarten through 12th grade. RESULTS: All
      states permit students to carry and administer their inhalers at school, although
      each state differs in their development and implementation of policies for asthma
      self-management at school. This review examines how states regulate self-carry
      policies by looking at policy development, regulated school systems, relevant
      stakeholders, required medical records, and school liability. CONCLUSIONS: Each
      state's laws have nuances that create gray areas, increasing the potential of
      misinterpreted or incorrectly implemented policies for asthma self-management at
      school. As a result, children may not have immediate access to their inhaler for
      symptom management or in an emergency. State policymakers should reform current
      laws to remove barriers for students to carry and use inhalers at school.

PMID- 30203482
TI  - The Influence of Active Gaming on Cardiorespiratory Fitness in Black and Hispanic
      Youth.
AB  - BACKGROUND: Youth in the United States have low levels of cardiorespiratory
      fitness, a risk factor for childhood obesity. Lower levels of physical fitness
      for black and Hispanic youth contribute to health disparities. In this
      feasibility study, we examined active video games (AVGs) as a tool to improve
      fitness and attitudes toward physical activity during early adolescence. METHOD:
      A 6-week AVG program took place in a youth development program in a high-poverty
      neighborhood in New York City. Youth aged 10 to 15 years (50% overweight or
      obese) participated in 2 fitness tests and completed surveys that captured
      barriers to physical activity pre- and postintervention. Each week, participants
      played Wii Fit games for 30 minutes. RESULTS: Participants improved the number of
      sit-ups and step-ups they completed from pre- to postintervention (p < .05).
      Participants also increased their self-efficacy, intention to exercise and
      perceived social support to exercise (p < .05). Youth reported a high level of
      enjoyment and perceived Wii Fit as ways to increase physical fitness and increase
      their physical activity. CONCLUSION: AVGs may be a viable alternative exercise
      program to increase physical activity for black and Hispanic youth living in
      poverty-impacted neighborhoods.

PMID- 30203484
TI  - Effect of Cardiorespiratory Fitness on Academic Achievement is Stronger in High
      SES Elementary Schools Compared to Low.
AB  - BACKGROUND: Academic achievement is influenced by factors at the student, school,
      and community levels. We estimated the effect of cardiorespiratory fitness
      performance on academic performance at the school level in Georgia elementary
      schools and examined effect modification by sociodemographic factors. METHODS:
      This study is a repeat cross-sectional analysis of Georgia elementary schools
      between 2011 and 2014 (approximately 1138 schools per year). Multivariable beta
      regression estimated the effect of the proportion of 4th and 5th graders meeting
      cardiorespiratory fitness standards on the proportion of 5th graders passing
      standardized tests for Reading, English and Language Arts, Mathematics, Science,
      and Social Studies and considered potential interaction by school-level
      socioeconomic status (SES), racial composition, and urbanity. RESULTS: There was
      a 0.15 higher estimated odds (OR: 1.15 (1.09, 1.22)) of passing the mathematics
      standardized test for every 10-percentage-point increase in school-level
      cardiorespiratory fitness among high-SES schools and 0.04 higher odds (OR: 1.04
      (1.02, 1.05)) for low-SES schools. This pattern was similar for other academic
      subjects. No effect modification by racial composition or urbanity was observed
      for any academic subject. CONCLUSIONS: Promoting physical fitness may be
      effective in improving academic performance among high-SES schools, but
      additional strategies may be needed among lower-SES schools.

PMID- 30203486
TI  - Analysis of variance.

PMID- 30203485
TI  - HDAC1/2-mediated regulation of JNK and ERK phosphorylation in bovine mammary
      epithelial cells in response to TNF-alpha.
AB  - Bovine mammary epithelial cells (MAC-Ts) are a common cell line for the study of
      mammary epithelial inflammation; these cells are used to mechanistically
      elucidate molecular underpinnings that contribute to bovine mastitis. Bovine
      mastitis is the most prevalent form of disease in dairy cattle that culminates in
      annual losses of two billion dollars for the US dairy industry. Thus, there is an
      urgent need for improved therapeutic strategies. Histone deacetylase (HDAC)
      inhibitors are efficacious in rodent models of inflammation, yet their role in
      bovine mammary cells remain unclear. HDACs have traditionally been studied in the
      regulation of nucleosomal DNA, in which deacetylation of histones impact
      chromatin accessibility and gene expression. Using MAC-T cells stimulated with
      tumor necrosis factor alpha (TNF-alpha) as a model for mammary cell inflammation,
      we report that inhibition of HDACs1 and 2 (HDAC1/2) attenuated TNF-alpha-mediated
      inflammatory gene expression. Of note, we report that HDAC1/2-mediated
      inflammatory gene expression was partly regulated by c-Jun N-terminal kinase
      (JNK) and extracellular signal-regulated kinase (ERK) phosphorylation. Here, we
      report that HDAC1/2 inhibition attenuated JNK and ERK activation and thus
      inflammatory gene expression. These data suggest that HDACs1 and 2 regulate
      inflammatory gene expression via canonical (i.e., gene expression) and
      noncanonical (e.g., signaling dependent) mechanisms. Whereas, further studies
      using primary cell lines and animal models are needed. Our combined data suggest
      that HDAC1/2-specific inhibitors may prove efficacious for the treatment of
      bovine mastitis.

PMID- 30203487
TI  - Upregulated long noncoding RNA LINC01296 indicates a dismal prognosis for
      pancreatic ductal adenocarcinoma and promotes cell metastatic properties by
      affecting EMT.
AB  - BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease that
      responds poorly to chemotherapy and radiotherapy and whose incidence has
      increased worldwide. Long noncoding RNAs have been demonstrated to play important
      roles in cancer initiation and progression. Long intergenic non-coding RNA 01296
      (LINC01296) has been reported to be upregulated in several malignancies, but the
      clinical relevance and biological role of LINC01296 in PDAC are still unclear.
      METHODS: RT-qPCR was performed to evaluate the expression of LINC01296 in 85
      pared PDAC tissue samples and a panel of PDAC cell lines. The clinical value and
      prognostic role of LINC01296 in patients with PDAC were further explored.
      Furthermore, we explored the functional roles of LINC01296 depletion in PANC-1
      and SW1990 cells, including cell proliferation, apoptosis, migration, invasion,
      and epithelial-to-mesenchymal transition (EMT). RESULTS: LINC01296 was enhanced
      in PDAC tissues and cell lines, and this overexpression was correlated with
      advanced tumor stages and positive lymph node metastasis in patients with PDAC.
      In addition, upregulation of LINC01296 was an independent prognostic predictor
      for patients with PDAC after surgery. Moreover, silencing of LINC01296 followed
      by treatment with small interfering RNAs suppressed cell proliferation and
      promoted cell apoptosis by affecting the Bcl-2/caspase-3 pathway. Importantly,
      LINC01296 attenuation impaired the migratory and invasive potential partly by
      reversing EMT. CONCLUSIONS: Overall, our work may help to develop a novel
      prognostic biomarker and therapeutic target for PDAC.

PMID- 30203488
TI  - Prognostic role of TPD52 in acute myeloid leukemia: A retrospective multicohort
      analysis.
AB  - Generating accurate prognoses is extremely important for treating patients with
      cancer. Prognostic prediction based on messenger RNA (mRNA) expression has shown
      superior clinical value to other markers for some cancers but is not currently
      used for acute myeloid leukemia (AML). Lipid metabolism is associated with
      biological aspects of cancer progression, including massive proliferation, and
      abnormal signaling. Moreover, abnormalities in lipid metabolism have prognostic
      significance. Patients with AML display abnormalities in sphingolipid metabolism
      and fatty acid oxidation. TPD52 is a regulator of lipid metabolism and plays a
      role in the formation of lipid droplets and fatty acid storage. Although the
      prognostic significance of TPD52 expression has been reported for many types of
      cancer, it has not yet been assessed in patients with AML. Therefore, the aim of
      the current study was to assess the prognostic significance of TPD52 in AML using
      three independent AML cohorts: one from The Cancer Genome Atlas (TGCA; n = 142)
      and two from the National Center for Biotechnology Information: GSE12417 (GPL96
      97; n = 162) and GSE12417 (GPL570; n = 78). TPD52 was found to be overexpressed
      in patients with AML (GSE84881; n = 23). The Kaplan-Meier curve revealed that
      TPD52 overexpression was associated with a poor prognosis for patients with AML
      with good discrimination ( P = 0.013, P = 0.005, and P = 0.032 for the TGCA,
      GSE12417, and GSE12417, respectively). Analysis of C-indices and area under the
      receiver operating characteristic curve values further supported this
      discriminative ability. Moreover, multivariate analysis confirmed the prognostic
      significance of TPD52 expression levels ( P = 0.0196). These results suggest that
      the TPD52 mRNA level is a potential biomarker for AML.

PMID- 30203489
TI  - Safety and efficacy of vismodegib in relapsed/refractory acute myeloid leukaemia:
      results of a phase Ib trial.

PMID- 30203490
TI  - Comprehensive analysis of novel three-long noncoding RNA signatures as a
      diagnostic and prognostic biomarkers of human triple-negative breast cancer.
AB  - Currently, traditional predictors of prognosis (tumor size, nodal status,
      progesterone receptor [PR], estrogen receptor [ER], or human epidermal growth
      factor receptor-2 [HER2]) are insufficient for precise survival prediction for
      triple-negative breast cancer (TNBC). Long noncoding RNAs (lncRNAs) have been
      observed to exert critical functions in cancer, including in TNBC. Nevertheless,
      systematically tracking expression-based lncRNA biomarkers based on the sequence
      data for the prediction of prognosis in TNBC has not yet been investigated. To
      ascertain whether biomarkers exist that can distinguish TNBC from adjacent normal
      tissue or nTNBC, we implemented a comprehensive analysis of lncRNA expression
      profiles and clinical data of 1097 BC samples from The Cancer Genome Atlas
      database. A total of 1510 differentially expressed lncRNAs in normal and TNBC
      samples were extracted. Similarly, 672 differentially expressed lncRNAs between
      nTNBC and TNBC samples were detected. The receiver operating characteristic curve
      analysis indicated that three upregulated lncRNAs (AC091043.1, AP000924.1, and
      FOXCUT) may be of strong diagnostic value for predicting the existence of TNBC in
      the training and validation sets (area under the curve (AUC > 0.85). Kaplan-Meier
      analysis demonstrated that the other three lncRNAs (AC010343.3, AL354793.1, and
      FGF10-AS1) were associated with the prognosis of TNBC patients (P < 0.05). We
      used the three overall survival (OS)-related lncRNAs to establish a three-lncRNA
      signature. Multivariate Cox regression analysis suggested that the three-lncRNA
      signature was a prognostic factor independent of other clinical variables ( P <
      0.01) for predicting OS in TNBC patients that could be utilized to classify
      patients into high- or low-risk subgroups. Our results might provide efficient
      signatures for clinical diagnosis and prognostic evaluation of TNBC.

PMID- 30203491
TI  - Iatrogenic cerebral gas embolism-A systematic review of case reports.
AB  - BACKGROUND: Cerebral gas embolism is a complication of several medical procedures
      and occurs when gas enters the cerebral circulation. Knowledge about etiology and
      outcome in affected patients is limited, and prospective trials on management and
      treatment are hardly feasible. Case reports are therefore an important source of
      information. METHODS: A systematic literature search was conducted in June 2016
      and May 2018, supplemented by a manual search. Titles and abstracts were
      systematically assessed for eligibility, followed by full-text screening for
      included papers. Screening and data extraction were performed independently by
      two researchers. Cases of cerebral gas embolism due to any iatrogenic cause were
      included. Criteria for exclusion were: animal studies, non-cerebral localization,
      extravascular gas only, and non-iatrogenic causes. 264 cases reported in 189
      papers were included. RESULTS: A broad range of procedures leading to iatrogenic
      cerebral gas embolism (ICGE) were identified and a comprehensive list is
      presented in this article. Procedures were mostly reported as conducted
      correctly, but procedure related error, patient activity, or defective equipment
      were also reported as causes. Neurological, neuropsychological, and
      cardiopulmonary symptoms were common. The diagnosis was frequently based on or
      confirmed by radiology, usually CT. Hyperbaric oxygen therapy was applied in a
      large number of cases. CONCLUSION: The reported causes, symptoms and signs, and
      outcomes of ICGE vary significantly, and awareness of the condition in the
      medical community is essential. A standardized method of reporting could
      facilitate higher quality research in the field.

PMID- 30203492
TI  - Comparison of different approaches for dose response analysis.
AB  - Characterizing an appropriate dose-response relationship and identifying the
      right dose in a clinical trial are two main goals of early drug-development. MCP
      Mod is one of the pioneer approaches developed within the last 10 years that
      combines the modeling techniques with multiple comparison procedures to address
      the above goals in clinical drug development. The MCP-Mod approach begins with a
      set of potential dose-response models, tests for a significant dose-response
      effect (proof of concept, PoC) using multiple linear contrasts tests and selects
      the "best" model among those with a significant contrast test. A disadvantage of
      the method is that the parameter values of the candidate models need to be fixed
      a priori for the contrasts tests. This may lead to a loss in power and unreliable
      model selection. For this reason, several variations of the MCP-Mod approach and
      a hierarchical model selection approach have been suggested where the parameter
      values need not be fixed in the proof of concept testing step and can be
      estimated after the model selection step. This paper provides a numerical
      comparison of the different MCP-Mod variants and the hierarchical model selection
      approach with regard to their ability of detecting the dose-response trend, their
      potential to select the correct model and their accuracy in estimating the dose
      response shape and minimum effective dose. Additionally, as one of the approaches
      is based on two-sided model comparisons only, we make it more consistent with the
      common goals of a PoC study, by extending it to one-sided comparisons between the
      constant and alternative candidate models in the proof of concept step.

PMID- 30203493
TI  - Early Enteral Nutrition Adequacy Mitigates the Neutrophil-Lymphocyte Ratio
      Improving Clinical Outcomes in Critically Ill Surgical Patients.
AB  - BACKGROUND: Neutrophil-lymphocyte ratio (NLR) is a measure of host inflammatory
      response; a higher NLR is associated with worse clinical outcomes. Enteral
      nutrition (EN) may mitigate inflammation through interaction with gut-associated
      lymphoid tissue. We hypothesized that early EN adequacy in critically ill
      surgical patients is associated with lower NLR and better clinical outcomes.
      METHODS: In this retrospective study, we analyzed data from adult surgical
      intensive care unit (ICU) patients receiving EN. NLR at baseline ICU admission
      (NLR-B), NLR after 3-5 days of EN (F-NLR), nutrition adequacy, caloric deficit
      (CD), protein deficit (PD), hospital length of stay (LOS), ICU LOS, 28-day
      ventilator-free days (28-VFD), and in-hospital mortality were collected. Tertiles
      groups were created for NLR, F-NLR, CD, and PD; the highest (H) and lowest (L)
      tertiles were compared. Regression analyses were performed to control for effect
      of age, gender, APACHE II, and NLR. RESULTS: Subjects in the L-CD group had lower
      median F-NLR (7 [range, 5-11] vs 10 [7-22], P = 0.005) and shorter ICU LOS (9 [6
      16]) vs 16 [9-32] days; P = 0.006). The L-NLR group had shorter hospital LOS (18
      [10-31] vs 22 [15-38] days, P = 0.023), greater 28-VFD (23 [18-25] vs 19 [11-22]
      days, P = 0.005), and lower in-hospital mortality (13% vs 41%, P = 0.002).
      CONCLUSION: In critically ill surgical patients, early enteral caloric adequacy
      is associated with less inflammation and improved clinical outcomes.

PMID- 30203494
TI  - Study design and outcomes measures: The influence of composite endpoints and
      other design variables on outcomes in a study of a novel device for stress
      urinary incontinence.
AB  - OBJECTIVES: To perform a post hoc analysis of the outcome data from a phase III
      study of a novel incontinence therapy for female stress incontinence (SUI) and to
      understand the pitfalls inherent to performing trials in SUI. METHODS: Results of
      the SUCCESS Trial, a multicenter, prospective, single-blinded, randomized, sham
      controlled study were assessed post hoc for parameters and variables consistent
      with changes in the symptoms or signs of SUI. Subjects were randomized to either
      the investigative device (Vesair Balloon) placement or placebo. The efficacy
      endpoint analysis herein evaluated a composite of both a >50% reduction from
      baseline on 1-hour provocative pad weight test and a >=10-point improvement in
      symptoms on the Incontinence Quality of Life (I-QOL) questionnaire assessed at
      the three-month study visit. Further analysis was performed utilizing more
      challenging success criteria for each endpoint and a subset of subjects with more
      severe baseline symptoms. RESULTS: The three-month composite efficacy endpoint
      was achieved in 42.1% of treatment group subjects compared with 28.1% of control
      subjects on an intention-to-treat analysis (P = .046). This difference between
      groups was not evident when analyzing each component of the composite endpoint
      separately. These endpoints diverged from endpoints involving improvement in PGI
      I score and a 50% reduction of incontinence episode frequency as reported by
      subjects on a diary. CONCLUSIONS: Individual endpoints may not demonstrate a
      significant treatment effect as standalone SUI measures but may as components of
      a composite endpoint. Defining patient selection and outcomes assessments is a
      critical aspect of study design, experimental flaws, and therapeutic accuracy.

PMID- 30203495
TI  - Effect of autophagy gene DRAM on proliferation, cell cycle, apoptosis, and
      autophagy of osteoblast in osteoporosis rats.
AB  - OBJECTIVE: The research aimed at detecting the autophagy level of osteoblast in
      osteoporosis rat, and investigating the effect of autophagy gene damage-regulated
      autophagy modulator (DRAM) on osteoblast proliferation, cell cycle, apoptosis,
      and autophagy. METHODS: The level of osteocalcin (OCN) and C-telopeptide (CTX) in
      serum of ovariectomized (OVX) rats was detected by enzyme-linked immunosorbent
      assay (ELISA). The Oil Red-O staining was used to observing bone histological
      changes. The messenger RNA level and protein expression level of Runt-related
      transcription factor 2 (Runx2; osteoblast markers) and other autophagy-related
      genes were revealed using quantitative real-time polymerase chain reaction (qRT
      PCR) and western blot. The changes of autophagy in osteoblasts were detected by
      immunofluorescence staining. The following experiments were performed in
      osteoblasts of OVX rats through transfected with silencing DRAM to detecting cell
      proliferation, cell cycle, and apoptosis by Cell Counting Kit-8 assays and flow
      cytometry. RESULTS: The result of ELISA showed a significantly elevated of OCN
      and CTX in OVX rats as well a high fat content compared with sham-operated rats.
      The expression of Runx2 in bone of proximal tibia was higher by qRT-PCR and
      western blot analysis. The immunofluorescence staining and transmission electron
      microscope observe revealed that pcDNA3-DRAM could promote the autophagy in OVX
      rats. Besides that, overexpression of DRAM inhibited cell proliferation, promoted
      apoptosis, and enhanced autophagy in osteoblasts. The results of Oil Red-O
      staining indicated that overexpression of DRAM enhanced lipid accumulation in
      osteoporosis rats. CONCLUSIONS: The autophagy level of OVX rats was weakened, but
      overexpressed DRAM could increase the autophagy level of osteoblast, suppress
      proliferation, and induce apoptosis of osteoblast.

PMID- 30203496
TI  - Particulate matter 2.5 induced bronchial epithelial cell injury via activation of
      5'-adenosine monophosphate-activated protein kinase-mediated autophagy.
AB  - The impact of particulate matter 2.5 (PM2.5) on the respiratory system is a
      worldwide concern. However, the mechanisms by which PM2.5 causes disease are
      still unclear. In this study, we investigated the effect of PM2.5 on autophagy
      and studied the effect of PM2.5-induced autophagy and 5'-adenosine monophosphate
      activated protein kinase (AMPK) on cell proliferation, cell cycle, apoptosis,
      reactive oxygen species (ROS), and airway inflammation using human bronchial
      epithelial cells 16HBE140 cells. Results showed that exposure of cells to PM2.5
      at a concentration of 100 MUg/mL for 24 hours was most effective for inhibiting
      cell viability. PM2.5 induced cell arrest in the G0/G1 phase and increased
      mitochondrial membrane potential, ROS, and cell apoptosis with increasing
      concentration. PM2.5 downregulated cyclin D and matrix metallopeptidase-9 (MMP-9)
      expression but upregulated tissue inhibitor of metalloproteinases-1 (TIMP-1)
      expression, significantly promoted interleukin-6 (IL-6), and tumor necrosis
      factor-alpha (TNF-alpha) production, and enhanced the level and activation of
      AMPK. The levels of autophagy-related protein 5 (ATG5), Beclin-1, and LC3II/I
      were significantly increased by PM2.5. The activation of Unc-51-like autophagy
      activating kinase 1 was significantly inhibited by PM2.5. Moreover, ATG5
      knockdown inhibited PM2.5-induced autophagy, ROS, and cell apoptosis
      significantly. The expression of cyclin D, MMP-9, and TIMP-1 was reversed by ATG5
      suppression. PM2.5-induction of IL-6 and TNF-alpha was significantly inhibited by
      knockdown of ATG5. Thus, inhibition of autophagy protected the cells from PM2.5
      induced injury. PM2.5 induced injury in human bronchial epithelial cells via
      activation of AMPK-mediated autophagy, suggesting possible therapeutic targets
      for the treatment of respiratory diseases.

PMID- 30203497
TI  - Half blind superiority tests for clinical trials of anti-infective drugs.
AB  - This paper introduces a test of superiority of new anti-infective drug B over
      comparator drug A based on a randomized clinical trial. This test can be used to
      demonstrate assay (trial) sensitivity for noninferiority trials and rigorously
      tailor drug choice for individual patients. Our approach uses specialized
      baseline covariates XA ,XB , which should predict the benefits of drug A and drug
      B, respectively. Using a response surface model for the treatment effect, we test
      for superiority at the (XA ,XB ) point that is most likely to show superiority.
      We identify this point based on estimates from a novel half-blind pseudo
      likelihood, where we augment a blinded likelihood (mixed over the treatment
      indicator) with likelihoods for the overall success rates for drug A and drug B
      (mixed over XA ,XB ). The augmentation results in much better estimates than
      those based on the mixed blinded likelihood alone but, interestingly, the
      estimates almost behave as if they were based on fully blinded data. We also
      develop an analogous univariate method using XA for settings where XB has little
      variation. Permutation methods are used for testing. If the "half-blind" test
      rejects, pointwise confidence interval can be used to identify patients who would
      benefit from drug B. We compare the new tests to other methods with an example
      and via simulations.

PMID- 30203498
TI  - Experimental anal infection of rainbow trout with Flavobacterium psychrophilum: A
      novel challenge model.

PMID- 30203499
TI  - Completely nonfluoroscopic catheter ablation of left atrial arrhythmias and
      ventricular tachycardia.
AB  - INTRODUCTION: Fluoroscopy use during catheter ablation procedures increases the
      cumulative lifetime radiation exposure of patients and operators, potentially
      leading to a higher risk of cancer and radiation-related injuries.
      Nonfluoroscopic ablation (NFA) has been described for supraventricular
      tachycardia, typical atrial flutter, paroxysmal atrial fibrillation (AF), and
      outflow-tract ventricular tachycardia (VT). Complete transition to NFA of more
      complex arrhythmias, including persistent AF, left atrial (LA) flutter, and
      structural VT, has not been previously described. We describe the transition to
      completely NFA of complex arrhythmias, including LA flutter and structural VT.
      The techniques, challenges, limitations, and results are described. METHODS AND
      RESULTS: Complex ablation procedures were performed using intracardiac
      echocardiography (ICE) and a three-dimensional mapping system without fluoroscopy
      or lead protection. Eighty consecutive patients underwent NFA (mean age, 60.1 +/-
      9.9 years, 70 with LA arrhythmias, 10 with VT). All cases were performed without
      the need for rescue fluoroscopy. There was an initial increase in procedural time
      for ablation of LA arrhythmias upon transitioning to NFA. However, after
      excluding the first 20 NFA cases to allow for operator learning, the transition
      to NFA was not associated with an increase in mean procedural time (229 +/- 38 vs
      225 +/- 32 minutes; P = 0.002 for noninferiority). All procedures were completed
      successfully with no complications. CONCLUSIONS: NFA of most complex arrhythmias
      (persistent AF, LA flutter, and structural VT) is feasible, with a modest
      learning curve and no increase in procedural times.

PMID- 30203500
TI  - Patient blood management in colorectal cancer patients: a survey among Dutch
      gastroenterologists, surgeons, and anesthesiologists.
AB  - INTRODUCTION: There is an increasing awareness to integrate patient blood
      management (PBM) within routine surgical care. Limited information about the
      implementation of PBM in colorectal cancer surgery is available. This is curious,
      as preoperative anemia, associated with increased morbidity, is highly prevalent
      in colorectal cancer patients. Present study aimed to assess the current PBM
      strategies in the Netherlands. METHODS: An online electronic survey was developed
      and sent to surgeons of the Dutch Taskforce Coloproctology (177 in total). In
      addition, for each hospital in which surgery for colorectal cancer surgery is
      performed (75 in total), the survey was sent to one gastroenterologist and one
      anesthesiologist. Analyses were performed using descriptive statistics. RESULTS:
      A total of 192 physicians responded to the survey (response rate 58.7%). In 73
      hospitals (97.3%) the survey was conducted by at least one physician. Regarding
      the management of a mild-moderate preoperative anemia, no clear policy was
      reported in half of the hospitals (49.3%). In 38.7% of the hospitals, iron status
      was indicated to be measured during screening for colorectal cancer. In addition,
      in only 13.3% of the hospitals, iron status was measured by the anesthesiologist
      during preoperative assessment. CONCLUSION: The Present study shows a distinct
      variability in PBM practices in colorectal cancer care. Strikingly, this
      variability was not only seen between, but also within Dutch hospitals,
      demonstrated by often variable responses from physicians from the same
      institution. As a result, the present study clearly demonstrates the lack of
      consensus on PBM, resulting in a suboptimal preoperative blood management
      strategy.

PMID- 30203501
TI  - Waveform analysis of the fetal ECG in labor in patients with intrahepatic
      cholestasis of pregnancy.
AB  - AIM: Intrahepatic cholestasis of pregnancy (ICP) is reported to be associated
      with an increased risk of sudden fetal death. The possible mechanism is thought
      to be cardiac arrhythmia. Prolonged QT interval of the electrocardiogram (ECG) is
      associated with arrhytmogenic events. The aim of the study was to compare the
      fetal ECG QT interval during labor in pregnancies complicated with ICP to healthy
      controls. METHODS: The fetal ECG and QT interval was reviewed retrospectively.
      The intrapartum QT interval was measured in 61 fetuses born to mothers with ICP
      and in a control group of similar size. The corrected QT interval (QTc) was
      calculated using Bazett's formula: QT/?RR. The occurrence of ST segment
      depression was also included in the analysis. RESULTS: The groups were similar
      regarding to maternal age, parity, BMI, gestational age and smoking habits. The
      rate of labor induction was significantly higher in ICP patients (P < 0.001). The
      QTc at the beginning and the end of recording was analyzed and there were no
      significant differences in these values between the ICP patients and healthy
      controls (P = 0.467). Most ICP patients used ursodeoxycholic acid (UDCA) for
      mediation. We analyzed separately patients who had elevated liver enzymes before
      labor. No significant differences in the QTc were noted in these patients either.
      Nor were there any significant ST depressions in ICP patients. CONCLUSIONS: The
      etiology of adverse perinatal outcome and even sudden fetal death in ICP is still
      controversial. No differences in QTc intervals and ST waveforms during labor were
      found in our study material.

PMID- 30203502
TI  - Nobiletin inhibits hypoxia-induced epithelial-mesenchymal transition in renal
      cell carcinoma cells.
AB  - Hypoxia is a universal characteristic of solid tumor and involving cancer
      metastasis via epithelial-mesenchymal transition (EMT). Nobiletin (3',4',5,6,7,8
      hexamethoxyflavone), a dietary polymethoxylated flavonoid found in citrus fruits,
      has been reported to have anticancer effects. However, the possible role of
      nobiletin in renal cell carcinoma (RCC) remains unclear. Thus, the aim of this
      study was to identify the effect of nobiletin on hypoxia-induced EMT in RCC
      cells. We found that nobiletin significantly inhibited the migration and invasion
      induced by hypoxia in RCC cells. In addition, nobiletin reversed the hypoxia
      induced EMT process in RCC cells. Furthermore, nobiletin suppressed the
      activation of NF-kappaB and Wnt/beta-catenin signaling pathways in hypoxia
      stimulated RCC cells. In conclusion, these findings demonstrate that nobiletin
      inhibits hypoxia-induced EMT in human RCC cells via the inactivation of the NF
      kappaB and Wnt/beta-catenin signaling pathways.

PMID- 30203503
TI  - Gadolinium-based contrast agents and Infertility.

PMID- 30203505
TI  - Risk of red cell exposure to the water anomaly upon blood unit cold-storage.

PMID- 30203504
TI  - Native kidney cytomegalovirus nephritis and cytomegalovirus prostatitis in a
      kidney transplant recipient.
AB  - We present a case of cytomegalovirus (CMV) native kidney nephritis and
      prostatitis in a CMV D+/R- kidney transplant recipient who had completed six
      months of CMV prophylaxis four weeks prior to the diagnosis of genitourinary CMV
      disease. The patient had a history of benign prostatic hypertrophy and urinary
      retention that required self-catheterization to relieve high post-voiding
      residual volumes. At 7 months post-transplant, he was found to have a urinary
      tract infection, moderate hydronephrosis of the transplanted kidney, and severe
      hydroureteronephrosis of the native left kidney and ureter, and underwent native
      left nephrectomy and transurethral resection of the prostate. Histopathologic
      examination of kidney and prostate tissue revealed CMV inclusions consistent with
      invasive CMV disease. This case highlights that CMV may extend beyond the kidney
      allograft to involve other parts of the genitourinary tract, including the native
      kidneys and prostate. Furthermore, we highlight the tissue-specific risk factors
      that preceded CMV tissue invasion. In addition to concurrent diagnoses, health
      care providers should have a low threshold for considering late-onset CMV disease
      in high-risk solid organ transplant recipients presenting with signs and symptoms
      of genitourinary tract pathology.

PMID- 30203506
TI  - How do career barriers and supports impact nurse professional commitment and
      professional turnover intention?
AB  - AIMS: This study examines how career barriers and supports (i.e., perceived
      discrimination, lack of advancement, human capital, and social capital) impact
      affective, normative, and continuance aspects of professional commitment and thus
      nurses' professional turnover intention. BACKGROUND: Professional commitment is
      known to influence professional turnover intention. However, little is known
      about how career barriers and supports contribute to professional commitment and
      reduce professional turnover intention. METHODS: This study adopted a cross
      sectional design and a survey to collect representative data in a major hospital
      in northern Taiwan. We used proportionate random sampling to ensure sample
      representativeness and obtained 524 responses. RESULTS: Perceived discrimination
      and lack of advancement were negatively related to affective professional
      commitment. Human capital was positively related to affective, normative, and
      continuance professional commitment. Social capital was positively related to
      normative professional commitment. All aspects of professional commitment were
      negatively related to professional turnover intention. CONCLUSION: Career
      barriers and supports have an important influence on professional commitment.
      Reduced barriers and enhanced support may therefore help reduce nurses'
      professional turnover intentions. IMPLICATIONS FOR NURSING MANAGEMENT: Nursing
      managers could aim to lessen career barriers while increasing career support for
      nurses, helping strengthen nurses' professional commitment and retention.

PMID- 30203508
TI  - NEAT1 contributes to ox-LDL-induced inflammation and oxidative stress in
      macrophages through inhibiting miR-128.
AB  - Long noncoding RNAs (lncRNA) have been recognized as significant regulators in
      the progression of atherosclerosis (AS). Oxidized low-density lipoprotein (ox
      LDL) can induce macrophage inflammation and oxidative stress, that serves
      important roles in AS. However, the exact function of lncRNA NEAT1 and its
      possible molecular mechanism in AS remain unclear. Here, we concentrated on the
      roles and molecular mechanisms of NEAT1 in AS development. In our current study,
      we observed that NEAT1 was elevated by ox-LDL in a dose-dependent and time
      dependent manner. RAW264.7 cell survival was greatly enhanced, and cell apoptosis
      was significantly inhibited by LV-shNEAT1 transfection. In addition, knockdown of
      NEAT1 in RAW264.7 cells repressed CD36 expression and foam cell formation while
      NEAT1 overexpression shown an opposite process. Moreover, NEAT1 downregulation
      inhibited inflammation molecules including IL-6, IL-1beta, and TNF-alpha.
      Meanwhile, silencing of NEAT1 can also suppress reactive oxygen species (ROS) and
      malondialdehyde (MDA) levels with an enhancement of superoxide dismutase (SOD)
      activity in RAW264.7 cells. MicroRNAs are some short RNAs, and they can regulate
      multiple biological functions in many diseases including AS. Here, we found that
      miR-128 expression was remarkably decreased in ox-LDL-incubated RAW264.7 cells.
      Interestingly, miR-128 mimics was able to reverse AS-correlated events induced by
      overexpression of NEAT1. By using bioinformatics analysis, miR-128 was predicted
      as a target of NEAT1 and the correlation between them was validated in our study.
      Taken these together, it was implied that NEAT1 participated in ox-LDL-induced
      inflammation and oxidative stress in AS development through sponging miR-128.

PMID- 30203507
TI  - The role of surgery in refractory epilepsy secondary to polymicrogyria in the
      pediatric population.
AB  - OBJECTIVE: Polymicrogyria (PMG) is a common malformation of cortical development.
      Many patients with PMG will have medically refractory epilepsy but the role of
      epilepsy surgery is unclear. The objective of this study was to assess the
      efficacy of surgical resection/disconnection in achieving seizure control in
      pediatric patients with PMG. METHODS: A retrospective review of children
      undergoing epilepsy surgery for PMG between 2002 and 2017 at The Hospital for
      Sick Children in Toronto, Canada, was performed. RESULTS: A total of 12 children
      aged 6 months to 17.8 years (median 8.8 years) underwent resective surgery (7
      children) or functional hemispherectomy (5 children). Gross total resection or
      complete disconnection of PMG was carried out in 7 of 12 children. Follow-up
      duration was between 1 and 9 years (median 2.1 years). Nine children remained
      seizure-free at last follow-up. Complete resection or disconnection of PMG led to
      seizure freedom in 6 of 7 patients (86%), whereas subtotal resection produced
      seizure freedom in 3 of 5 patients (60%). SIGNIFICANCE: We present one of the
      largest surgical series of pediatric PMG patients. Seizure outcomes were best
      with complete resection/disconnection of PMG. However, tailored resections based
      on electroclinical and neuroradiologic data can produce good outcomes and remain
      an appropriate strategy for patients with extensive PMG.

PMID- 30203509
TI  - The maximum detrusor pressure as a predictive factor of success after
      sphincterotomy in detrusor-sphincter dyssynergia.
AB  - AIMS: To evaluate the impact of the pre-operative maximum detrusor pressure (MDP)
      on efficacy outcomes after incontinentation by sphincterotomy or urethral stent
      placement in male patients with neurogenic detrusor-sphincter dyssynergia (DSD).
      METHODS: A retrospective study was performed in 41 male patients treated between
      2006 and 2013 in a tertiary reference center. All patients had a neurogenic DSD
      confirmed by baseline urodynamic studies, and were unable or secondary failed to
      practice CISC. Success was defined as a post-void residual volume <150 mL.
      Influence of MDP on treatment efficacy was evaluated through a Mann-Whitney U
      Test. RESULTS: Median (range) age was 39 years (20-69). Spinal cord injury was
      the main underlying condition. Twenty-six patients had a sphincteric stent
      placement (Memocath(r), Bard, Covington) and 15 had surgical sphincterotomy.
      Treatment was successful in 31 patients (76%). Patients with immediate successful
      outcomes had a significantly higher mean preoperative MDP (59.6 vs 29.7 cmH2 O; P
      = 0.002). Patients with MDP over the threshold of 40 cmH2 O had a 90% success
      rate. These differences were maintained at 6 months, MDP being higher in the
      success group than in the failure group (59.5 vs 39.8 cmH2 O, respectively, P =
      0.008). The technique used (stent placement or incision) had no impact on
      immediate or 6-month success rates. CONCLUSIONS: Our results suggested that MDP
      is associated with treatment success rate after surgical management of DSD of
      neurogenic origin by sphincteric stent placement or surgical sphincterotomy. A
      threshold of 40 mH2 O is associated with higher success rates.

PMID- 30203510
TI  - A survey on usage of personal care products especially cosmetics among university
      students in Saudi Arabia.
AB  - BACKGROUND: The harmful health effects of personal care products especially
      cosmetics have engulfed many societies of the world especially the female section
      without an alarm. OBJECTIVES: To estimate the prevalence of cosmetic usage and to
      assess the experiences of Saudi female undergraduate students in Wadi Al Dawasir
      province in an attempt to arouse general awareness among Saudi students about the
      harmful effects of the chemicals present therein. METHODOLOGY: It is a cross
      sectional study carried out with a total of randomly selected 106 college
      students (female) at undergraduate level. Two colleges for girls of Prince Sattam
      Bin Abdul Aziz University at Wadi Al Dawasir region were included. Standard
      questionnaire was set in Arabic and English both. T test and data was analyzed
      using SPSS version 20. Chi-square/Fisher's exact tests and a P value of <0.05
      were considered statistically significant. RESULTS: The overall prevalence of
      using cosmetics (makeup) and average age of first use of the cosmetics was found
      to be quite high. Statistical analysis shows that 69.8% students applied daily
      and 23.6% students applied twice to thrice daily. Consequently, this makes a
      gross percentage of 93.4% among college going Saudi students who applied makeup
      on daily basis. The findings have shown that 93.2% female and married medical
      students use cosmetics twice/thrice daily. Similarly, 6.8% female and married
      medical students use cosmetics once daily. The findings have shown that 82.9%
      female and unmarried medical students possess knowledge about cosmetics.
      Similarly, 17.1% female and married medical students possess knowledge about
      cosmetics. CONCLUSION: The usage of cosmetics was found to be extremely high
      among the college going Saudi students in Wadi Al Dawasir Region, Kingdom of
      Saudi Arabia. Un-awareness regarding the harmful effects of cosmetics was found
      to be high among these students.

PMID- 30203511
TI  - Titanium-Carboxylate Metal-Organic Framework Based on an Unprecedented Ti-Oxo
      Chain Cluster.
AB  - Titanium(IV)-based metal-organic frameworks (Ti-MOFs) have received significant
      attention in recent years due to their numerous photocatalytic applications. We
      herein prepare the single-crystalline Ti-carboxylate MOF (DGIST-1) composed of an
      unprecedented Ti-oxo chain cluster and the porphyrinic ligand, TCPP (tetrakis(4
      carboxyphenyl)porphyrin). Preformed Ti-oxo clusters were used as Ti4+ sources to
      avoid the spontaneous hydrolysis and condensation reactions of traditional Ti
      alkoxide precursors, thus, enabling the formation of the highly crystalline Ti
      MOF. The successfully activated DGIST-1 exhibited a higher surface area (i.e.,
      1957.3 m2  g-1 ) than previously reported Ti-MOFs due to its high crystallinity.
      Furthermore, the visible-light-responsive photocatalytic activity of DGIST-1 was
      confirmed by the simultaneous generation of singlet oxygen (1 O2 ) and superoxide
      (. O2 - ) species, in addition to the highly efficient and selective oxidation of
      benzyl alcohol to benzaldehyde.

PMID- 30203512
TI  - Dietary Unsaturated Fatty Acids Modulate Maternal Dyslipidemia-Induced DNA
      Methylation and Histone Acetylation in Placenta and Fetal Liver in Rats.
AB  - The present study assessed the role of dietary unsaturated fatty acids in
      maternal dyslipidemia-induced DNA methylation and histone acetylation in placenta
      and fetal liver and accumulation of lipids in the fetal liver. Weanling female
      Wistar rats were fed control and experimental diets for 2 months, mated, and
      continued on their diets during pregnancy. At gestation days of 18-20, rats were
      euthanized to isolate placenta and fetal liver. DNA methylation, DNA methyl
      transferase-1 (DNMT1) activity, acetylation of histones (H2A and H2B), and
      histone acyl transferase (HAT) activity were evaluated in placenta and fetal
      liver. Fetal liver lipid accumulation and activation of peroxisome proliferator
      activated receptor-alpha (PPAR-alpha) were assessed. Maternal dyslipidemia caused
      significant epigenetic changes in placenta and fetal liver. In the placenta, (1)
      global DNA methylation increased by 37% and DNMT1 activity by 86%, (2) acetylated
      H2A and H2B levels decreased by 46% and 24% respectively, and (3) HAT activity
      decreased by 39%. In fetal liver, (1) global DNA methylation increased by 52% and
      DNMT1 activity by 78%, (2) acetylated H2A and H2B levels decreased by 28% and 26%
      respectively, and (3) HAT activity decreased by 37%. Maternal dyslipidemia caused
      a 4.75-fold increase in fetal liver triacylglycerol accumulation with a 78%
      decrease in DNA-binding ability of PPAR-alpha. Incorporation of dietary
      unsaturated fatty acids in the maternal high-fat diet significantly (p < 0.05)
      modulated dyslipidemia-induced effects in placenta and fetal liver.
      Eicosapentaenoic acid (EPA, 20:5n-3) + docosahexaenoic acid (DHA, 22:6n-3)
      exhibited a profound effect followed by alpha-linolenic acid (ALA, 18:3n-3) than
      linoleic acid (LNA, 18:2n-6) in modulating the epigenetic parameters in placenta
      and fetal liver.

PMID- 30203513
TI  - Downregulation of AC061961.2, LING01-AS1, and RP11-13E1.5 is associated with
      dilated cardiomyopathy progression.
AB  - This study aimed to explore long noncoding RNAs (lncRNAs) implicated in dilated
      cardiomyopathy (DCM). Ten samples of failing hearts collected from the left
      ventricles of patients with DCM undergoing heart transplants, and ten control
      samples obtained from normal heart donors were included in this study. After
      sequencing, differentially expressed genes (DEGs) and lncRNAs between DCM and
      controls were screened, followed with functional enrichment analysis and weighted
      gene coexpression network analysis (WGCNA). Five key lncNRAs were validated
      through real-time polymerase chain reaction (PCR). Total 1,398 DEGs were
      identified, including 267 lncRNAs. WGCNA identified seven modules that were
      significantly correlated with DCM. The top 50 genes in the three modules (black,
      dark-green, and green-yellow) were significantly correlated with DCM disease
      state. Four core enrichment lncRNAs, such as AC061961.2, LING01-AS1, and RP11
      557H15.4, in the green-yellow module were associated with neurotransmitter
      secretion. Five core enrichment lncRNAs, such as KB-1299A7.2 and RP11-13E1.5, in
      the black module were associated with the functions of blood circulation and
      heart contraction. AC061961.2, LING01-AS1, and RP11-13E1.5 were confirmed to be
      downregulated in DCM tissues by real-time PCR. The current study suggests that
      downregulation of AC061961.2, LING01-AS1, and RP11-13E1.5 may be associated with
      DCM progression, which may serve as key diagnostic biomarkers and therapeutic
      targets for DCM.

PMID- 30203514
TI  - Kidney protective effects of baroreflex activation therapy in patients with
      resistant hypertension.
AB  - Baroreflex activation therapy (BAT) is approved for the treatment of resistant
      hypertension. In addition to blood pressure (BP) reduction, pilot studies
      suggested several organoprotective effects of BAT. Thirty-two patients with
      resistant hypertension were prospectively treated with BAT. Besides office BP and
      24-hour ambulatory BP (ABP) measurements, detection of a urinary proteome-based
      classifier (CKD273), which has been shown to predict chronic kidney disease (CKD)
      progression, was carried out at baseline and after 6 months of BAT. Office BP
      significantly decreased from 170 +/- 25/90 +/- 18 to 149 +/- 29/82 +/- 18 mm Hg.
      Analysis of CKD273 score and eGFR with CKD-EPI equation at baseline revealed
      strong correlation (r = 0.568, P < 0.001). After 6 months of BAT, there was no
      significant change in CKD273 score (-0.061 [95% CI: -0.262 to 0.140], P = 0.601).
      However, by stratification of the data regarding ABP response, there was a
      statistically significant (P = 0.0113) reduction in the CKD273 score from a mean
      of 0.161 [95% CI: -0.093 to 0.414] to -0.346 [95% CI: -0.632 to -0.060] after BAT
      in patients with systolic ABP decrease of >=5 mm Hg. These data emphasized
      potential nephroprotective effects of BAT in patients with sufficient BP
      response.

PMID- 30203515
TI  - Lithium Electrochemical Tuning for Electrocatalysis.
AB  - Electrocatalysis is of great importance to a variety of energy conversion
      processes, where developing highly efficient catalysts is critical. While common
      strategies involve screening a wide range of materials with new chemical
      compositions or structures, a different approach to continuously, controllably,
      and effectively tune the electronic properties of existing catalytic materials
      for optimized activities has been demonstrated recently. Inspired by studies in
      lithium-ion batteries, systematical lithium electrochemical tuning (LiET) methods
      such as Li intercalation, extraction, cycling, and strain engineering, are
      employed to effectively tune the electronic structures of different existing
      catalysts and thus improve their catalytic activities dramatically. Herein, the
      advantages of the LiET method in electrocatalysis are introduced, and then some
      recent representative examples in improving the performances of important
      electrochemical reactions are reviewed briefly. Lastly, a few promising
      directions on extending the applications of the LiET method in electrocatalysis
      are proposed.

PMID- 30203516
TI  - Upper-limb contracture development in children with cerebral palsy: a population
      based study.
AB  - AIM: The aim of this study was to investigate the longitudinal development of
      passive range of motion (ROM) in the upper limbs in a population-based sample of
      children with cerebral palsy (CP), and to investigate which children are more
      likely to develop contractures related to functional level, CP subtype, and age.
      METHOD: Registry data of annual passive ROM measurements of the upper limbs from
      771 children with CP (417 males, 354 females; mean age 11y 8mo, [SD 5mo] range 1
      18y) were analysed. Mixed models were used to investigate at what age decreased
      passive ROM occurs. Odds ratios were calculated to compare risks and logistic
      regression analysis was used to predict contracture development. RESULTS: Thirty
      four per cent of the children had developed contractures. Among these children,
      decreased passive ROM was significant at a mean age of 4 years for wrist
      extension and 7 years for shoulder flexion, elbow extension, and supination.
      Children at Manual Ability Classification System (MACS) level V had a 17-times
      greater risk of contractures than children at MACS level I. INTERPRETATION: One
      third of the children in the total population developed upper-limb contractures
      while passive ROM decreased with age. MACS level was the strongest predictor of
      contracture development. WHAT THIS PAPER ADDS: In a population-based sample of
      771 children with cerebral palsy, 34% developed an upper-limb contracture.
      Contracture development started at preschool age. The first affected movements
      were wrist extension and supination. Passive range of motion decreased with age.
      High Manual Ability Classification System level was the most important predictor
      of contractures.

PMID- 30203518
TI  - The karrikin 'calisthenics': can compounds derived from smoke help in stress
      tolerance?
AB  - Karrikins (KARs) are unique butenolides derived as a by-product of incomplete
      combustion during wildfire. Some receptive plant species respond to KARs in the
      form of accelerated germination. These molecules originate from stress to mediate
      tolerance against different sub-optimal conditions like oxidative stress, drought
      and low-light intensity (shade stress). KARs promote seed germination, seedling
      establishment and ecological diversity by accelerating the abundance of selective
      communities of plants. The signaling pathway is closely related, yet unique from
      strigolactones (SLs). Due to the structural relatedness with SLs, KARs have
      potential roles in mediating abiotic stress tolerance in plants. In addition, the
      KAR directly/indirectly interact with crucial phytohormones like abscisic acid,
      gibberellic acid, auxins and ethylene. This article is a summarized update on KAR
      research in recent times. The exhaustive discussions would be beneficial for
      understanding the extraordinary strategy devised by nature to protect plants from
      stress using a molecule which is itself generated out of stress.

PMID- 30203517
TI  - Oral health trajectories in community-dwelling older adults in the last 3 years
      of life.
AB  - BACKGROUND: Systemic health and physical, cognitive, and social function
      gradually decline at the end of life. How oral health change at the end of life
      in community-dwelling older adults remains unknown, increasing the difficulty in
      treatment planning for these individuals. METHODS: A total of 250 community
      dwelling decedents of a longitudinal study were included in the analysis.
      Decedents' clinical and interview data collected at baseline, 18, 36, 60, and 84
      months were linked to their death dates and plotted on an inverted time scale to
      study their oral health changes in the 3 years prior to death. Mixed effect
      models with random intercepts and slopes of months from death and
      sociodemographic variables were used to model the subjective and objective oral
      health trajectories in the last 3 years of life. The association of the change in
      the outcomes with a linear trend of months from death were assessed using the F
      test. RESULTS: Number of missing teeth was significantly associated with a linear
      trend of months from death. With every month in proximity to death, the expected
      number of missing teeth increased by 0.03 (SE = 0.004; p < 0.001), resulting in
      an average of 1.08 missing teeth in 3 years. Among subjective outcomes, the odds
      of good versus poor or "neither" self-rated systemic health (p = 0.009) and mouth
      appearance (p = 0.008) significantly decreased as death approached. CONCLUSION:
      Although other oral health measures remained relatively stable, tooth loss and
      dissatisfaction with mouth appearance steadily increased in community-dwelling
      older adults as death approached. These changes were gradual and parallel the end
      of-life general health decline.

PMID- 30203519
TI  - Incorporating Heavy Alkanes in Metal-Organic Frameworks for Optimizing Adsorbed
      Natural Gas Capacity.
AB  - Metal-organic frameworks (MOFs) as methane adsorbents are highly promising
      materials for applications such as methane-powered vehicles, flare gas capture,
      and field natural gas separation. Pre- and post-synthetic modification of MOFs
      have been known to help improve both the overall methane uptake as well as the
      working capacity. Here, a post-synthetic modification strategy to non-covalently
      modify MOF adsorbents for the enhancement of the natural gas uptake for the MOF
      material is introduced. In this study, PCN-250 adsorbents were doped with C10
      alkane and C14 fatty acid and their impact on the methane uptake capabilities was
      investigated. It was found that even trace amounts of heavy hydrocarbons could
      considerably enhance the raw methane uptake of the MOF while still being
      regenerable. The doped hydrocarbons are presumably located at the mesoporous
      defects of PCN-250, thus optimizing the framework-methane interactions. These
      findings reveal a general approach that can be used to modify the MOF absorbents,
      improving their ability to be sustainable and renewable natural gas adsorption
      platforms.

PMID- 30203520
TI  - Leadless multisite pacing: A feasibility study using wireless power transfer
      based on Langendorff rodent heart models.
AB  - INTRODUCTION: Fifteen to thirty percent of patients with impaired cardiac
      function have ventricular dyssynchrony and warrant cardiac resynchronization
      therapy (CRT). While leadless pacemakers eliminate lead-related complications,
      their current form factor is limited to single-chamber pacing. In this study, we
      demonstrate the feasibility of multisite, simultaneous pacing using miniaturized
      pacing nodes powered through wireless power transfer (WPT). METHODS: A wireless
      energy transfer system was developed based on resonant coupling at approximately
      200 MHz to power multiple pacing nodes. The pacing node comprises circuitry to
      efficiently convert the harvested energy to output stimuli. To validate the use
      of these pacing nodes, ex vivo studies were carried out on Langendorff rodent
      heart models (n = 4). To mimic biventricular pacing, two beating Langendorff
      rodent heart models, kept 10 cm apart, were paced using two distinct pacing
      nodes, each attached on the ventricular epicardial surface of a given heart.
      RESULTS: All ex vivo Langendorff heart models were successfully paced with a
      simple coil antenna at 2 to 3 cm from the pacing node. The coil was operated at
      198 MHz and 0.3 W. Subsequently, simultaneous pacing of two Langendorff heart
      models 30 cm apart using an output power of 5 W was reliably demonstrated.
      CONCLUSION: WPT provides a feasible option for multisite, wireless cardiac
      pacing. While the current system remains limited in design, it offers support and
      a conceptual framework for future iterations and eventual clinical utility.

PMID- 30203521
TI  - Finding Nemo's Genes: A chromosome-scale reference assembly of the genome of the
      orange clownfish Amphiprion percula.
AB  - The iconic orange clownfish, Amphiprion percula, is a model organism for studying
      the ecology and evolution of reef fishes, including patterns of population
      connectivity, sex change, social organization, habitat selection and adaptation
      to climate change. Notably, the orange clownfish is the only reef fish for which
      a complete larval dispersal kernel has been established and was the first fish
      species for which it was demonstrated that antipredator responses of reef fishes
      could be impaired by ocean acidification. Despite its importance, molecular
      resources for this species remain scarce and until now it lacked a reference
      genome assembly. Here, we present a de novo chromosome-scale assembly of the
      genome of the orange clownfish Amphiprion percula. We utilized single-molecule
      real-time sequencing technology from Pacific Biosciences to produce an initial
      polished assembly comprised of 1,414 contigs, with a contig N50 length of 1.86
      Mb. Using Hi-C-based chromatin contact maps, 98% of the genome assembly were
      placed into 24 chromosomes, resulting in a final assembly of 908.8 Mb in length
      with contig and scaffold N50s of 3.12 and 38.4 Mb, respectively. This makes it
      one of the most contiguous and complete fish genome assemblies currently
      available. The genome was annotated with 26,597 protein-coding genes and contains
      96% of the core set of conserved actinopterygian orthologs. The availability of
      this reference genome assembly as a community resource will further strengthen
      the role of the orange clownfish as a model species for research on the ecology
      and evolution of reef fishes.

PMID- 30203522
TI  - Health care reform in Iran: Implications for nurses' moral distress, patient
      rights, satisfaction and turnover intention.
AB  - AIM: The aim of the present study was to assess the implications of Iran's recent
      health care reforms on nurses' experience of moral distress, their perceptions of
      the respect for patient rights and the relationship of these variables to job and
      income dissatisfaction and turnover intention. BACKGROUND: Health systems around
      the world are reforming themselves to adapt to meeting the future needs of
      increasing patient care to an ever-growing population. METHODS: This was a cross
      sectional correlational study. The participants were 276 nurses at six large
      private and public hospitals in Tehran, Iran. FINDINGS: Negative correlations
      were reported between turnover intention and respecting patient rights (r = 
      0.560, p < 0.001), satisfaction with job (r = -0.710, p < 0.001) and satisfaction
      with income (r = -0.226, p < 0.001). The correlation between moral distress
      intensity (r = 0.626, p < 0.001) and frequency (r = 0.701, p < 0.001) was
      positive with turnover intention. CONCLUSIONS: Moral distress was significantly
      correlated to poor respect for patient rights, poor job satisfaction and income
      satisfaction and was a major predictor of turnover intention. IMPLICATIONS FOR
      NURSING MANAGEMENT: Health system reform must take into account the concomitant
      increasing workload and its negative impact in order to ensure that reform does
      not lead to unintentional detrimental outcomes of increased moral distress,
      decreased satisfaction and increased turnover rates among nursing personnel.

PMID- 30203523
TI  - Effect of drying conditions on the quality of IRGA 424 rice.
AB  - BACKROUND: The objective of this research was to investigate the effects of
      drying temperature (40, 50, and 60  degrees C), tempering time (40, 80, and 120
      min), and initial moisture content at onset of tempering (15, 17, and 19% dry
      basis) on head rice yield, milled rice yield, and total processing time of IRGA
      424 rice. RESULTS: The most significant effects were the drying temperature and
      its interaction with initial moisture content at onset of tempering. The optimum
      conditions predicted to reach the highest total yield (74.1%) included drying at
      46.6  degrees C, 49 min of tempering time, and initial moisture content at onset
      of tempering of 19%. To achieve the maximum value of whole grain yield (52.9%),
      drying at 40  degrees C, 40 min of tempering, and an initial moisture content of
      19% at the initiation of tempering were required. Under these conditions, the
      grain reached a moisture content of 13% in 84 min. CONCLUSION: Whole-grain rice
      yields may be maximized through the optimization of the drying process. This may
      result in a larger fraction of the crop entering the human food chain, enhancing
      the value of the crop, and resulting in a smaller fraction of broken grain, which
      commands a lower market value. (c) 2018 Society of Chemical Industry.

PMID- 30203524
TI  - LINC00657 expedites neuropathic pain development by modulating miR-136/ZEB1 axis
      in a rat model.
AB  - Long non-coding RNAs (lncRNAs) are involved in the progression of several
      diseases. The interactions among lncRNAs, microRNA (miRNAs) or their targeting
      genes are reported to play crucial roles in the development of diseases.
      LINC00657 is observed to be upregulated in several cancers. However, the
      biological role of LINC00657 in neuropathic pain progress is unclear. Hence, in
      our study, we aimed to investigate the function of LINC00657 in neuropathic pain
      development. A chronic constriction injury (CCI) rat model was established, and
      we found that LINC00657 was greatly increased in CCI rats associated with a
      decrease of miR-136. Inhibition of LINC00657 suppressed neuropathic pain via
      alleviating mechanical and thermal hyperalgesia. In addition, miR-136
      overexpression can also inhibit the neuropathic pain development. MiR-136 was
      predicted to serve as a miRNA target of LINC00657, and dual-luciferase reporter
      assay confirmed the correlation between LINC00657 and miR-136. Moreover, we
      observed that the decrease of LINC00657 was able to inhibit the neuroinflammation
      of CCI rats by targeting expression of cyclooxygenase-2, tumor necrosis factor
      alpha and interleukin-1beta while miR-136 inhibitors reversed this phenomenon.
      Next, by using bioinformatics analysis, ZEB1 was predicted as a direct target of
      miR-136, and miR-136 could negatively modulate ZEB1 expression. Besides these,
      ZEB1 was remarkably increased in the CCI rats. Knockdown of ZEB1 can inhibit
      neuropathic pain development, while miR-136 inhibitors can reverse it. In
      conclusion, it was implied that LINC00657 can induce the neuropathic pain
      development via regulating miR-136/ZEB1 axis.

PMID- 30203525
TI  - The effects of outcome unit framing on delay discounting.
AB  - We examined the effects of outcome framing on delay discounting. In Experiment 1,
      participants completed four delay-discounting tasks. In one monetary task, money
      was framed in units of dollars ($50), and in the other, money was framed in units
      of handfuls of quarters (equal to $50). In one food task, food was framed in
      clear units of food (e.g., 100 M&Ms), and in the other, food was framed in units
      of servings (e.g., 10 servings of M&Ms). When money was framed in units of
      dollars, participants discounted less by delay compared to discounting of
      handfuls of quarters. When food was framed as clear units, participants also
      discounted less compared to how they discounted servings. In Experiment 2,
      participants completed two delay-discounting tasks for dollars and quarters
      (e.g., $50 or 200 quarters) to determine if the results of Experiment 1 were due
      to the differences in handling costs. In one delay-discounting task, money was
      framed in units of dollars. In the other delay-discounting task, money was framed
      in units of quarters. There was no difference in how participants discounted
      delayed money framed as dollars or quarters. Clear unit framing may result in
      less discounting by delay than fuzzy unit framing.

PMID- 30203527
TI  - Spotlights on our sister journals: Angew. Chem. Int. Ed. 38/2018.

PMID- 30203526
TI  - Accessory spleen mimicking an intra-abdominal tumour.

PMID- 30203528
TI  - An Alternative to Lithium Metal Anodes: Non-dendritic and Highly Reversible
      Sodium Metal Anodes for Li-Na Hybrid Batteries.
AB  - Highly reversible, stable, and non-dendritic metal anode (Li, Na etc.) is a
      crucial requirement for next-generation high-energy batteries. Herein, we have
      built a Li-Na hybrid battery (LNHB) based on Na plating/stripping, which features
      a high and stable coulombic efficiency of 99.2 % after 100 cycles, low voltage
      hysteresis (42 mV at 2 mA cm-2 ), and fast charge transfer. As a result of the
      Li+ electrostatic shield layer, the Na deposition showed cubic morphology rather
      than dendritic, even at high current density of 5 mA cm-2 . The
      solvation/desolvation of Li+ and Na+ were modelled by density functional theory
      calculations, demonstrating the fast desolvation kinetics of Na+ . Owing to the
      superior performance of the Na metal anode, the LNHB coupled with LiFePO4 cathode
      exhibited low voltage hysteresis and stable cycling performance that demonstrates
      its feasibility in practical applications.

PMID- 30203529
TI  - Disruption of the redox balance with either oxidative or anti-oxidative
      overloading as a promising target for cancer therapy.
AB  - Oxidative stress acts as a double-edged sword by being both a promoter and a
      suppressor of cancer. Moderate oxidative stress is beneficial for cancer cell
      proliferative and invasiveness features, while overexposure of the cells to
      oxidative insults could induce cancer cell apoptosis and reduce hypoxia along
      with modulating the immune system for regression of tumor. Cancer cells and
      cancer stem cells have highly efficient redox systems that make them resistant to
      oxidative insults. The redox disruptive approach is an area of current research
      and key for oxidative targeted cancer therapies. This disruption is applicable by
      using either oxidative or anti-oxidative overloading strategies, specifically on
      cancer cells without influencing normal cells or tissues around tumor. The
      activity of tumor suppressor cells within tumor microenvironment is needed to be
      maintained in patients receiving such approaches.

PMID- 30203530
TI  - Comparison of corneal biomechanical changes after refractive surgery by
      noncontact tonometry: small-incision lenticule extraction versus flap-based
      refractive surgery - a systematic review.
AB  - Corneal refractive surgery disrupts corneal integrity and reduces biomechanical
      stability in consequence of the beneficial refractive alteration. The minimal
      invasive cap-based refractive procedure, small-incision lenticule extraction
      (SMILE), has been proposed to affect corneal integrity less than flap-based
      procedures, due to the fibre-sparing incision of the strong anterior corneal
      lamellae. Flap-based procedures include laser-assisted in situ keratomileusis
      (LASIK), femtosecond laser-assisted in situ keratomileusis (FS-LASIK) and
      femtosecond lenticule extraction (FLEx). The purpose of this systematic review
      was to evaluate corneal biomechanical changes by noncontact air pulse tonometry
      after treatment of myopia/myopic astigmatism with SMILE compared to flap-based
      refractive surgery. A total of 220 publications were identified through a
      systematic search in PubMed and Embase. Two levels of screening identified nine
      studies (three randomised controlled trials (RCT) and six nonrandomised clinical
      trials) eligible for the review. All the nonrandomised clinical trials were
      graded to have an overall serious risk of bias. Measurements with the Corvis ST
      were not included in any of the eligible studies. The RCTs found no statistical
      significant differences between SMILE or flap-based procedures concerning corneal
      hysteresis (CH) or corneal resistance factor (CRF), as measured with the Ocular
      Response Analyzer. However, a greater reduction in CRF and CH was found in the
      flap-based group in five and two of the nonrandomised studies, respectively. The
      findings in this review illustrate that the presumed biomechanical advantages of
      a cap-based small incision could not be demonstrated in existing studies and by
      commercially available technology. However, studies with lower levels of evidence
      suggest less affection of corneal viscoelastic properties after SMILE when
      evaluating corneal stability by noncontact tonometry.

PMID- 30203531
TI  - Mitochondrial permeability regulates cardiac endothelial cell necroptosis and
      cardiac allograft rejection.
AB  - Transplantation is invariably associated with programmed cell death including
      apoptosis and necrosis, resulting in delayed graft function and organ rejection.
      We have demonstrated the contribution of necroptosis to mouse microvascular
      endothelial cell (MVEC) death and transplant rejection. Organ injury results in
      the opening of mitochondrial permeability transition pores (mPTPs), which can
      trigger apoptotic molecules release that ultimately results in cell death. The
      effect of mPTPs in the necroptotic pathway remains controversial; importantly,
      their role in transplant rejection is not clear. In this study, tumor necrosis
      factor-alpha triggered MVECs to undergo receptor-interacting protein kinase
      family (RIPK1/3)-dependent necroptosis. Interestingly, inhibition of mPTP opening
      could also inhibit necroptotic cell death. Cyclophilin-D (Cyp-D) is a key
      regulator of the mPTPs. Both inhibition and deficiency of Cyp-D protected MVECs
      from necroptosis (n = 3, P < .00001). Additionally, inhibition of Cyp-D
      attenuated RIPK3-downstream mixed-lineage kinase domain-like protein
      phosphorylation. In vivo, Cyp-D-deficient cardiac grafts showed prolonged
      survival in allogeneic BALB/c mice posttransplant compared with wild-type grafts
      (n = 7, P < .0001). Our study results suggest that the mPTPs may be important
      mechanistic mediators of necroptosis in cardiac grafts. There is therapeutic
      potential in targeting cell death via inhibition of the mPTP-regulating molecule
      Cyp-D to prevent cardiac graft rejection.

PMID- 30203533
TI  - Predicting coral community recovery using multi-species population dynamics
      models.
AB  - Predicting whether, how, and to what degree communities recover from disturbance
      remain major challenges in ecology. To predict recovery of coral communities we
      applied field survey data of early recovery dynamics to a multi-species integral
      projection model that captured key demographic processes driving coral population
      trajectories, notably density-dependent larval recruitment. After testing model
      predictions against field observations, we updated the model to generate
      projections of future coral communities. Our results indicated that communities
      distributed across an island landscape followed different recovery trajectories
      but would reassemble to pre-disturbed levels of coral abundance, composition, and
      size, thus demonstrating persistence in the provision of reef habitat and other
      ecosystem services. Our study indicates that coral community dynamics are
      predictable when accounting for the interplay between species life-history,
      environmental conditions, and density-dependence. We provide a quantitative
      framework for evaluating the ecological processes underlying community trajectory
      and characteristics important to ecosystem functioning.

PMID- 30203532
TI  - Spectroscopic and metal binding properties of a de novo metalloprotein binding a
      tetrazinc cluster.
AB  - De novo design provides an attractive approach, which allows one to test and
      refine the principles guiding metalloproteins in defining the geometry and
      reactivity of their metal ion cofactors. Although impressive progress has been
      made in designing proteins that bind transition metal ions including iron-sulfur
      clusters, the design of tetranuclear clusters with oxygen-rich environments
      remains in its infancy. In previous work, we described the design of
      homotetrameric four-helix bundles that bind tetra-Zn2+ clusters. The crystal
      structures of the helical proteins were in good agreement with the overall
      design, and the metal-binding and conformational properties of the helical
      bundles in solution were consistent with the crystal structures. However, the
      corresponding apo-proteins were not fully folded in solution. In this work, we
      design three peptides, based on the crystal structure of the original bundles.
      One of the peptides forms tetramers in aqueous solution in the absence of metal
      ions as assessed by CD and NMR. It also binds Zn2+ in the intended stoichiometry.
      These studies strongly suggest that the desired structure has been achieved in
      the apo state, providing evidence that the peptide is able to actively impart the
      designed geometry to the metal cluster.

PMID- 30203534
TI  - A pilot study comparing the efficacy of two formulations of botulinum toxin type
      A for muscular calves contouring.
AB  - BACKGROUND: Enlarged, hypertrophy calf muscles are common in Asian women and can
      cause psychological burden. Botulinum toxin A (BTA) has been widely used in
      treating masseteric muscle hypertrophy and it's efficacious as a noninvasive
      method for calf-contouring has been reported. Food and Drug Administration has
      approved onabotulinumtoxin A (ONA, Botox; Allergan Inc, Irvine, CA, USA) for
      upper face rejuvenation and it has off-label uses for calf-contouring. A recently
      introduced Prabotulinumtoxin A (NABOTA(r) , PRA; Daewoong Pharmaceutical, Seoul,
      Korea) demonstrated a comparable efficacy and safety to ONA for masseter
      reduction. OBJECTIVE: To compare the efficacy and safety of PRA and ONA
      gastrocnemius muscle reduction. METHODS: This is an experimental, randomized,
      controlled double-blind study. Twenty-two patients were randomized to receive 100
      units PRA and ONA on each calf and were asked to come for follow-up visit for up
      to 6 months. Clinical photographic documentation, calf circumference measurement
      (upright position and tiptoe), isokinetic analysis, and ultrasonographic imaging
      were performed to evaluate the treatment result. In addition, patients'
      satisfaction and side effect were also recorded. RESULTS: All patients completed
      the study without serious side effect occurred during the whole study period. The
      mean calf circumference of the ONA- and PRA-treated patients in upright position
      at baseline was 35.42 +/- 1.35 cm and 36.49 +/- 2.98 cm, respectively (P =
      0.137). The mean calf circumference in upright position decreased significantly
      as early as 2 weeks after treatment, both in ONA group and in PRA group (P =
      0.004 and P = 0.003, respectively), and continued to decrease until 6 months
      after treatment (P = 0.002 and P < 0.001, respectively). There was no
      statistically significant difference in mean calf circumference when comparing
      between ONA and PRA group at any time of follow-up period. For the tiptoe
      position, only in the PRA group that showed significant reduction as early as two
      weeks and lasted up to 6 months of follow-up (P < 0.001). The isokinetic analysis
      showed no significant reduction on both maximum torque and average work value in
      two groups. The ultrasonographic imaging revealed that the mean thickness of the
      lateral head of the gastrocnemius showed significant only in PRA-treated group at
      2-, 3-, and 6-months of follow-up; meanwhile, the mean thickness of the medial
      head showed significant reduction at 2- and 6-months, with a slight increase at 3
      months follow-up in two groups. The patients' satisfaction rate and doctor's
      evaluation also showed no statistically significant difference between both
      groups. CONCLUSION: This study demonstrated that PRA and ONA provided comparable
      efficacy and safety in gastrocnemius muscle reduction.

PMID- 30203536
TI  - Intranasal oxytocin fails to acutely improve glucose metabolism in obese men.
AB  - The hypothalamic neuropeptide oxytocin not only modulates psychosocial function,
      but also contributes to metabolic regulation. We have recently shown that
      intranasal oxytocin acutely improves beta-cell responsivity and glucose tolerance
      in normal-weight men. In the present experiment, we investigated the acute
      glucoregulatory impact of oxytocin in obese men with impaired insulin
      sensitivity. Fifteen obese healthy men with an average body mass index of 35
      kg/m2 and an average body fat content of 33% received a single intranasal dose
      (24 IU) of oxytocin before undergoing an oral glucose tolerance test. Results
      were analysed according to the oral minimal model and compared with our findings
      in normal-weight participants. In contrast to the results in normal-weight
      subjects, oxytocin did not blunt postprandial glucose and insulin excursions in
      obese men, and moreover failed to enhance beta-cell responsivity and glucose
      tolerance. These results indicate that pronounced obesity may be associated with
      a certain degree of resistance to the glucoregulatory impact of exogenous
      oxytocin, and underlines the need for further investigations into the potential
      of oxytocin to improve glucose homeostasis in the clinical context.

PMID- 30203535
TI  - Extracellular protease trypsin activates amiloride-insensitive sodium channels in
      human leukemia cells.
AB  - Sodium influx is tightly regulated in the cells of blood origin. Amiloride
      insensitive sodium channels were identified as one of the main sodium
      transporting pathways in leukemia cells. To date, all known regulatory pathways
      of these channels are coupled with intracellular actin cytoskeleton dynamics.
      Here, to search for physiological mechanisms controlling epithelial Na+ channel
      (ENaC)-like channels, we utilized leukemia K562 cells as a unique model to
      examine single channel behavior in a whole-cell patch-clamp experiments. We have
      shown for the first time that extracellular serine protease trypsin directly
      activates sodium channels in plasma membrane of K562 cells. The whole-cell single
      current recordings clearly demonstrate no inhibition of trypsin-activated
      channels by amiloride or benzamil. Involvement of proteolytic cleavage in channel
      opening was confirmed in experiments with soybean trypsin inhibitor. More
      importantly, stabilization of F-actin with intracellular phalloidin did not
      prevent trypsin-induced channel activation indicating no implication of
      cytoskeleton rearrangements in stimulatory effect of extracellular protease. Our
      data reveals a novel mechanism modulating amiloride-insensitive ENaC-like channel
      activity and integral sodium permeability in leukemia cells.

PMID- 30203537
TI  - Continued licensing of hydroxyethyl starch despite high-quality data documenting
      harm in vulnerable patient populations: A sad day for patient safety.

PMID- 30203538
TI  - Hydroxyethyl starch: A half-century enigma.

PMID- 30203539
TI  - Accidental hypothermia in recreational activities in the mountains: A narrative
      review.
AB  - The popularity of recreational activities in the mountains worldwide has led to
      an increase in the total number of persons exposed to cold and extreme
      environments through recreation. There is little conclusive evidence about the
      risk of hypothermia for specific activities or populations, nor is it clear which
      activities are represented in the literature. This is a non-systematic review of
      accidental hypothermia in different recreational activities in the mountains,
      with a specific focus on outdoor or winter activities that potentially involve
      cold exposure. Cases of hypothermia have been reported in the literature in
      mountaineering, trekking, hiking, skiing, activities performed in the
      backcountry, ultra-endurance events, and databases from search and rescue
      services that include various types of recreation. Of these activities,
      hypothermia as a primary illness occurs most commonly during mountaineering in
      the highest elevation areas in the world and during recreation practiced in more
      northern or remote areas. Hypothermia in skiers, snowboarders, and glacier-based
      activities is most often associated with accidents occurring off-piste or in the
      backcountry (crevasse, avalanche). Organizers of outdoor events also have a role
      in reducing the incidence of hypothermia through medical screening and other
      preparedness measures. More complete collection and reporting of data on mild
      hypothermia and temperature measurement would improve our understanding of the
      incidence of hypothermia in outdoor recreation in future.

PMID- 30203540
TI  - First record of the intermediate scabbardfish Aphanopus intermedius
      (Scombriformes: Trichiuridae) in the western South Atlantic Ocean.
AB  - This study reports on the first record of the intermediate scabbardfish Aphanopus
      intermedius in the western South Atlantic Ocean, based on a single specimen 725
      mm standard length collected between 0 and 610 m depth around Rocas Atoll off
      north-eastern Brazil. Measurements and counts are provided and compared with
      those available in the literature.

PMID- 30203541
TI  - Hierarchical FeCo2 S4 Nanotube Arrays Deposited on 3D Carbon Foam as Binder-free
      Electrodes for High-performance Asymmetric Pseudocapacitors.
AB  - The ever-increasing global demand for green energy resources calls for more
      research attention on the development of cheap and efficient energy storage
      systems. Herein, we propose the rational design of a 3D carbon foam electrode
      deposited with perpendicularly oriented FeCo2 S4 nanotubes arrays (FeCo2 S4 /CMF)
      for high-performance asymmetric supercapacitors. In this work, the macroporous
      CMF served as conducting backbone not only to enhance the electrical conductivity
      of the composite, but also to promote the uniform growth of FeCo2 S4 nanotubes.
      Deposited hierarchical FeCo2 S4 nanotubes arrays with open hollow structures can
      afford numerous exposed electroactive sites for Faradaic redox reaction and
      provide short interior channels for fast electrolyte transmission. Due to these
      unique features, obtained 3D hierarchical FeCo2 S4 /CMF composite foam exhibits a
      high specific capacitance of 2430 F g-1 (specific capacity of 337.5 mAh g-1 ) at
      1 A g-1 , and excellent capacitance retention of 91 % after 5000 cycles at a high
      current density of 9 A g-1 , which is superior to most of those previously
      reported binary metal sulfide-based electrodes. Moreover, asymmetric
      supercapacitor device assembled using the FeCo2 S4 /CMF as positive electrode
      also delivers a high energy density of 78.7 W h kg-1 at a power density of 800.3
      W kg-1 . Therefore, this work provides a new strategy for the low-cost synthesis
      of 3D foam electrodes towards high-performance supercapacitor devices.

PMID- 30203542
TI  - Value of Contrast-Enhanced Ultrasound in the Diagnosis of Renal Cancer and in
      Comparison With Contrast-Enhanced Computed Tomography: A Meta-analysis.
AB  - OBJECTIVES: The purpose of this meta-analysis was to assess the diagnostic
      accuracy of contrast-enhanced ultrasound (CEUS) in renal cancer and to compare it
      with contrast-enhanced computed tomography (CECT). METHODS: A systematic search
      was performed to recruit eligible original studies published until December 2017.
      Two reviewers independently extracted data. A meta-analysis was performed, and
      the pooled sensitivity, specificity, positive and negative likelihood ratios,
      positive and negative predictive values, diagnostic odds ratio, summary receiver
      operating characteristic curve, and area under the curve were calculated. The
      extent and potential sources of heterogeneity were further explored. Moreover, a
      head-to-head comparison was also performed to compare the diagnostic value
      between CEUS and CECT in renal cancer. RESULTS: Twenty-two studies were included
      in this meta-analysis. The summary sensitivity and specificity of CEUS for
      detecting renal cancer were 0.96 (95% confidence interval [CI], 0.94-0.97) and
      0.82 (95% CI, 0.74-0.88), respectively. The summary diagnostic odds ratio was
      102.04 (95% CI, 49.55-210.13). The area under the summary receiver operating
      characteristic curve was 0.97 (95% CI, 0.95-0.98). In the head-to-head
      comparison, CEUS showed higher diagnostic sensitivity than CECT (0.94 versus
      0.85) for renal cancer, whereas the specificities were comparable between CEUS
      and CECT (0.77 versus 0.75). CONCLUSIONS: Contrast-enhanced US has high
      sensitivity and moderate specificity in the differential diagnosis of renal
      cancer. The diagnostic sensitivity of CEUS in renal cancer was higher than that
      of CECT, suggesting that CEUS could be used as a preferred diagnostic tool for
      renal cancer.

PMID- 30203543
TI  - Structure versus function in high myopia using optical coherence tomography and
      automated perimetry.
AB  - BACKGROUND: To examine the structure-function relationship between retinal
      thickness using spectral-domain optical coherence tomography and standard
      automated perimetry in high myopia. METHODS: The study population comprised 58
      highly myopic individuals with no posterior abnormalities (mean spherical
      equivalent refraction <= -6.00 D and axial length >= 26.0 mm). All eyes underwent
      optical coherence tomography with the Spectralis spectral domain optical
      coherence tomograph and visual field evaluation with the Humphrey Field Analyzer
      II-i. Average macular layer thicknesses in each quadrant were calculated in a 6 *
      6 mm area centred on the fovea. The visual field was assessed from 17 central
      locations (10 degrees ), approximately the equivalent of the area tested by
      optical coherence tomography in the macular scan. Linear correlations were made
      between different macular layer thicknesses and peripapillary retinal nerve layer
      thickness with their matched visual field sensitivities. RESULTS: Participant
      ages were 28.2 +/- 6.4 years, mean spherical equivalent refractions were -8.20 +/
      1.40 D and axial lengths were 26.7 +/- 0.7 mm. There were significant positive
      correlations between layer thickness and corresponding visual field sensitivities
      as follows: ganglion cell layer in all quadrants, temporal quadrant of the nerve
      fibre layer with nasal quadrant of the visual field, inferior quadrant of the
      outer nuclear layer with superior visual field, and temporal-superior
      peripapillary nerve fibre layer with nasal-inferior visual field. CONCLUSION: The
      correlation between retinal layer thicknesses and visual field sensitivity could
      be explained by myopia-related losses due to lateral retinal stretching, with
      further research required to investigate this.

PMID- 30203544
TI  - Effects of preoperative hepatitis B virus infection, hepatitis C virus infection,
      and coinfection on the development of new-onset diabetes after kidney
      transplantation.
AB  - BACKGROUND: The effects of preoperative hepatitis B virus (HBV) infection,
      hepatitis C virus (HCV) infection, and HBV plus HCV coinfection on the
      development of new-onset diabetes after transplantation (NODAT) remain unexplored
      in kidney transplant recipients (KTRs). This study examined the association
      between preoperative viral status (i.e., HBV, HCV, and HBC + HCV infection) and
      incident NODAT in a large population of Chinese KTRs. METHODS: This population
      based retrospective cohort study enrolled 557 subjects who underwent kidney
      transplantation between 1993 and 2014 at Zhongshan Hospital. Pre-, peri-, and
      postoperative data were extracted and analyzed. Viral status was defined by
      serological results for hepatitis B surface antigen and anti-HCV antibody. The
      cumulative incidence of NODAT was compared across four groups of KTRs with
      different viral status. Multivariate Cox regression models were used to estimate
      the effects of HBV, HCV, and HBC + HCV infection on incident NODAT after
      adjusting for important confounders. RESULTS: Patients seropositive for HCV (both
      HCV monoinfection and HBC + HCV coinfection) had a significantly higher
      cumulative incidence of NODAT than KTRs who were not infected with HCV (P < 0.05
      for both). However, only HCV infection alone was found to be a risk factor for
      NODAT, increasing the NODAT risk 3.03-fold (95% confidence interval 1.77-5.18; P
      < 0.001). There was no independent correlation between HBV infection (alone or
      combined with HCV) and incident NODAT in KTRs. CONCLUSIONS: Preoperative HCV
      infection significantly increased the risk of NODAT in Chinese KTRs, whereas HBV
      infection and HBC + HCV coinfection were not correlated with NODAT development.

PMID- 30203545
TI  - Tyrosine phosphorylation signaling regulates Ca2+ entry by affecting
      intracellular pH during human sperm capacitation.
AB  - Capacitation is a mandatory process for the acquisition of mammalian sperm
      fertilization competence and involves the activation of a complex and still not
      fully understood system of signaling pathways. Under in vitro conditions, there
      is an increase in both protein tyrosine phosphorylation (pTyr) and intracellular
      Ca2+ levels in several species. In human sperm, results from our group revealed
      that pTyr signaling can be blocked by inhibiting proline-rich tyrosine kinase 2
      (PYK2). Based on the role of PYK2 in other cell types, we investigated whether
      the PYK2-dependent pTyr cascade serves as a sensor for Ca 2+ signaling during
      human sperm capacitation. Flow cytometry studies showed that exposure of sperm to
      the PYK2 inhibitor N-[2-[[[2-[(2,3-dihydro-2-oxo-1 H-indol-5-yl)amino]-5
      (trifluoromethyl)-4-pyrimidinyl]amino]methyl]phenyl]- N-methyl-methanesulfonamide
      hydrate (PF431396) produced a significant and concentration-dependent reduction
      in intracellular Ca 2+ levels during capacitation. Further studies revealed that
      PF431396-treated sperm exhibited a decrease in the activity of CatSper, a key
      sperm Ca 2+ channel. In addition, time course studies during capacitation in the
      presence of PF431396 showed a significant and sustained decrease in both
      intracellular Ca 2+ and pH levels after 2 hr of incubation, temporarily
      coincident with the activation of PYK2 during capacitation. Interestingly,
      decreases in Ca 2+ levels and progressive motility caused by PF431396 were
      reverted by inducing intracellular alkalinization with NH 4 Cl, without affecting
      the pTyr blockage. Altogether, these observations support pTyr as an
      intracellular sensor for Ca 2+ entry in human sperm through regulation of
      cytoplasmic pH. These results contribute to a better understanding of the
      modulation of the polymodal CatSper and signaling pathways involved in human
      sperm capacitation.

PMID- 30203546
TI  - Effect of progressive muscle relaxation on the caregiver burden and level of
      depression among caregivers of older patients with a stroke: A randomized
      controlled trial.
AB  - AIM: This study aimed to investigate the effect of progressive muscle relaxation
      on the caregiver burden and level of depression among the caregivers of older
      patients with a stroke. METHODS: This randomized, controlled experimental study
      was conducted between December, 2015 and July, 2017 with the caregivers of older
      patients with a stroke who had been admitted to the home care unit of a state
      hospital. The caregivers were randomly assigned to intervention (n = 23) and
      control (n = 21) groups, based on the study's inclusion criteria. The caregivers
      in the intervention group practiced progressive muscle relaxation exercises at
      home 3 days per week for 8 weeks. The control group had no intervention. RESULTS:
      The mean age of the older patients with a stroke was 80.15 +/- 9.86 years and the
      mean duration of the disease was 39.07 +/- 44.69 months. The mean age of the
      caregivers was 50.29 +/- 12.62 years, 84.1% of whom were female, 38.6% were
      elementary school graduates, and 86.4% were married. It was found that there was
      a statistically significant decrease in the mean Zarit Caregiver Burden Scale and
      Beck Depression Scale scores of the caregivers in the intervention group after
      practicing progressive muscle relaxation, but this decrease was not statistically
      significant when the intervention and control groups were compared. CONCLUSION:
      This study showed that there was a statistically significant decrease in the
      caregiver burden and level of depression among the caregivers in the intervention
      group after progressive muscle relaxation exercises, but that there was no
      statistically significant difference when the intervention and control groups
      were compared.

PMID- 30203547
TI  - NEAT1 induces osteosarcoma development by modulating the miR-339-5p/TGF-beta1
      pathway.
AB  - The long noncoding RNA (lncRNA) nuclear enriched abundant transcript 1 (NEAT1)
      has been recognized as a tumor oncogene involved in the development of multiple
      cancers. However, the function of NEAT1 and its molecular mechanism in
      osteosarcoma (OS) remain unclear. First, we detected the NEAT1 expression in OS
      cell lines by performing quantitative reverse-transcription polymerase chain
      reaction. Next, the effects of NEAT1 on OS cell growth, apoptosis, migration, and
      invasion were tested by lentivirus-mediated downregulation. We observed that
      inhibition of NEAT1 restrained OS cell progression greatly. Interestingly, in the
      last few years, increasing studies have shown that some lncRNAs can act as miRNA
      sponges and reduce the amount of the same. Here, we found that NEAT1 can modulate
      OS development via sponging miR-339-5p. MiR-339-5p was significantly decreased in
      OS cells, and its overexpression can remarkably repress the OS proliferation.
      These results indicated that NEAT1 could function as a tumor oncogene in OS by
      inhibiting miR-339-5p in vitro. Then, the following assays validated that
      transforming growth factor beta1 (TGF-beta1) can act as a functional target of
      miR-339-5p in OS cells. Finally, we indicated that NEAT1 could mediate TGF-beta1
      expression by competitively sponging miR-339-5p. NEAT1 induced OS cell
      proliferation and cell mobility by binding to miR-339-5p and increasing TGF-beta1
      in OS. It was demonstrated in our study that lncRNA NEAT1 could impede miR-339-5p
      expression to maintain the expression of TGF-beta1, which led to the development
      of OS. Our findings implied that the novel identified NEAT1/miR-339-5p/TGF-beta1
      axis might be a new molecular pathway or therapeutic target for OS diagnosis and
      treatment.

PMID- 30203548
TI  - Glycyrrhizin inactivates toll-like receptor (TLR) signaling pathway to reduce
      lipopolysaccharide-induced acute lung injury by inhibiting TLR2.
AB  - OBJECTIVE: This study aimed to explore glycyrrhizin on acute lung injury (ALI)
      and how glycyrrhizin (GL) attenuated lipopolysaccharide (LPS)-induced ALI.
      METHODS: Bioinformatics analysis was performed to screen the expressed genes in
      LPS-induced ALI mice. The enrichment of functions and signaling pathways of
      deregulated genes were conducted. Combined with DIGSEE and STICH, the target gene
      for further investigation was chosen. To verify target gene in mice, we performed
      experiment in vivo. Forty mice were randomized into NC, LPS, LPS + S, and LPS +
      GL group. Mice in the LPS + GL group received glycyrrhizin l mg and mice in LPS +
      S received saline. Then, HE and Masson staining detected pathological changes of
      lung tissues; enzyme-linked immunosorbent assay analyzed bronchoalveolar lavage
      fluid concentrations of MIP-2, mice growth-related oncogene homologue (KC), IL-4,
      IL-6, GM-CSF, IFN-gamma, and IgM; western blot analysis determined the expression
      of toll-like receptor (TLR) signaling and NF-kappaB pathway-related proteins.
      RESULTS: Tlr2 which was not only upregulated but also closely related to
      glycyrrhizin. TLR2 was upregulated in following LPS induced in cells and TLR2
      overexpression-activated TLR signaling pathway to promote ALI. After glycyrrhizin
      treatment, the expression of TLR2 was reduced. Furthermore, it was found out that
      the number of inflammatory cells, collagen deposition, MIP-2, KC, IL-4, IL-6, GM
      CSF, and IFN-gamma expression increased in ALI mice and glycyrrhizin mitigated
      it. Similarly, the expression of TLR signaling pathway and NF-kappaB pathway
      related protein also increased. CONCLUSION: Glycyrrhizin functioned as a
      suppressor in TLR signaling pathway to reduce LPS-induced ALI by inhibiting TLR2.

PMID- 30203549
TI  - A structural model of total quality management, work values, job satisfaction and
      patient-safety-culture attitude among nurses.
AB  - AIM: This study explores the impact of total quality management on patient-safety
      culture attitudes among clinical nurses, focusing on the correlations between
      total quality management, work values, employee satisfaction, and patient-safety
      culture attitudes. BACKGROUND: Implementing total quality management can improve
      nurses' attitudes towards patient-safety culture. METHOD: This hospital-based,
      cross-sectional survey used a convenience sample of 30 inpatient units and 12
      intensive care units at five Taiwanese regional teaching hospitals with over 500
      beds. Seven hundred questionnaires were distributed (140 to each hospital) during
      25 June-5 July 2015. Data were collected using an anonymous, self-administered,
      and structured questionnaire. The model was tested using structural equation
      modelling and serial mediation analysis. RESULTS: Of 515 completed questionnaires
      (73.6% response rate), 23 were invalid and 492 were used (70.3% retrieved rate).
      The total effect of total quality management on patient-safety-culture attitudes
      was significant via work values, which had a direct influence on patient-safety
      culture attitude. Total quality management affected employee satisfaction, which
      directly influenced patient-safety-culture attitudes. CONCLUSION: Total quality
      management creates a beneficial working environment and improves patient-safety
      culture. Total quality management, work values, and employee satisfaction
      orientation are important predictors of nurses' attitudes toward patient-safety
      culture attitudes. IMPLICATIONS FOR NURSING MANAGEMENT: Health care managers
      should cultivate nursing performance to achieve continuous quality improvement in
      nursing care.

PMID- 30203550
TI  - A Monte-Carlo-based and GPU-accelerated 4D-dose calculator for a pencil beam
      scanning proton therapy system.
AB  - PURPOSE: The presence of respiratory motion during radiation treatment leads to
      degradation of the expected dose distribution, both for target coverage and
      healthy tissue sparing, particularly for techniques like pencil beam scanning
      proton therapy which have dynamic delivery systems. While tools exist to estimate
      this degraded four-dimensional (4D) dose, they typically have one or more
      deficiencies such as not including the particular effects from a dynamic
      delivery, using analytical dose calculations, and/or using nonphysical dose
      accumulation methods. This work presents a clinically useful 4D-dose calculator
      that addresses each of these shortcomings. METHODS: To quickly compute the 4D
      dose, the three main tasks of the calculator were run on graphics processing
      units (GPUs). These tasks were (a) simulating the delivery of the plan using
      measured delivery parameters to distribute the plan amongst 4DCT phases
      characterizing the patient breathing, (b) using an in-house Monte Carlo
      simulation (MC) dose calculator to determine the dose delivered to each breathing
      phase, and (c) accumulating the doses from the various breathing phases onto a
      single phase for evaluation. The accumulation was performed by individually
      transferring the energy and mass of dose-grid subvoxels, a technique that models
      the transfer of dose in a more physically realistic manner. The calculator was
      run on three test cases, with lung, esophagus, and liver targets, respectively,
      to assess the various uncertainties in the beam delivery simulation as well as to
      characterize the dose-accumulation technique. RESULTS: Four-dimensional doses
      were successfully computed for the three test cases with computation times
      ranging from 4-6 min on a server with eight NVIDIA Titan X graphics cards; the
      most time-consuming component was the MC dose engine. The subvoxel-based dose
      accumulation technique produced stable 4D-dose distributions at subvoxel scales
      of 0.5-1.0 mm without impairing the total computation time. The uncertainties in
      the beam delivery simulation led to moderate variations of the dose-volume
      histograms for these cases; the variations were reduced by implementing
      repainting or phase-gating motion mitigation techniques in the calculator.
      CONCLUSIONS: A MC-based and GPU-accelerated 4D-dose calculator was developed to
      estimate the effects of respiratory motion on pencil beam scanning proton therapy
      treatments. After future validation, the calculator could be used to assess
      treatment plans and its quick runtime would make it easily usable in a future 4D
      robust optimization system.

PMID- 30203551
TI  - Catalpol inhibits TGF-beta1-induced epithelial-mesenchymal transition in human
      non-small-cell lung cancer cells through the inactivation of Smad2/3 and NF
      kappaB signaling pathways.
AB  - Catalpol, one of the main active ingredients isolated from Rehmannia glutinosa,
      was reported to possess anticancer activity. However, the role of catalpol in
      transforming growth factor beta1 (TGF-beta1)-induced epithelial-mesenchymal
      transition (EMT) in human non-small-cell lung cancer (NSCLC) cells has not been
      elucidated. The objective of this study was to investigate the effect of catalpol
      on EMT in human NSCLC cells. Our results showed that catalpol significantly
      inhibited the TGF-beta1-induced cell migration and invasion of A549 cells, as
      well as repressed matrix metalloproteinase (MMP)2 and MMP9 expression induced by
      TGF-beta1 in A549 cells. In addition, catalpol markedly repressed the EMT process
      in A549 cells in response to TGF-beta1. Furthermore, catalpol prevented the
      activation of Smad2/3 and nuclear factor kappaB (NF-kappaB) signaling pathways
      induced by TGF-beta1 in A549 cells. In conclusion, these findings indicated that
      catalpol inhibits TGF-beta1-induced EMT in human NSCLC cells through the
      inactivation of Smad2/3 and NF-kappaB signaling pathways. Thus, catalpol may be a
      promising agent for the treatment of NSCLC.

PMID- 30203552
TI  - A novel cell transfection platform based on laser optoporation mediated by Au
      nanostar layers.
AB  - The recently developed laser-induced cell transfection mediated by Au
      nanoparticles is a promising alternative to the well-established lipid-based
      transfection or to electroporation. Optoporation is based on the laser plasmonic
      heating of nanoparticles located near the cell membrane. However, the
      uncontrollable cell damage from intense laser pulses and from random attachment
      of nanoparticles may be crucial for transfection. We present a novel plasmonic
      optoporation technique that uses Au nanostar layers immobilized in culture
      microplate wells. HeLa cells were grown directly on Au nanostar layers, after
      which they were subjected to continuous-wave 808 nm laser irradiation. An Au
      monolayer density ~15 MUg/cm2 and an absorbed energy of about 15 to 30 J were
      found to be optimal for optoporation. Propidium iodide molecules were used as
      model penetrating agent. The transfection efficiency evaluated using fluorescence
      microscopy for HeLa cells transfected with pGFP under optimized optoporation
      conditions (95% +/- 5%) was similar to the efficiency of TurboFect. The
      technique's efficiency (295 +/- 10 relative light units, RLU), demonstrated by
      transfecting HeLa cells with the pCMV-GLuc 2 control plasmid, was greater than
      that obtained by transfection of HeLa cells with the TurboFect agent (220 +/- 10
      RLU). The cell viability in plasmonic optoporation (92% +/- 7%), too, was greater
      than that in transfection with TurboFect (75% +/- 7%).

PMID- 30203553
TI  - The effects of apheresis, storage time, and leukofiltration on microparticle
      formation in apheresis platelet products.
AB  - BACKGROUND: Although platelet microparticles (PMPs) were the most abundant
      micoparticles (MPs) in platelet (PLT) products, other MPs and their parental
      cells can also be brought into the plasma during PLT apheresis. However, the
      effects of PLT apheresis, storage time, and leukofiltration on these MPs remain
      largely unclear. STUDY DESIGN AND METHODS: Apheresis PLTs with or without
      leukofiltration were stored in 22 +/- 2  degrees C for 5 days. PLT-poor plasma
      (PPP) was generated by centrifugation of donor blood or PLT products at 2500 * g
      for 15 minutes on the point day. PPP was labeled with CD41a (PLT-derived MP,
      PMP), CD235 (red blood cell-derived MP, RMP), CD45 (leukocyte-derived MP, LMP),
      CD14 (monocyte-derived MP, MMP), and CD144 (endothelial cell-derived MP, EMP),
      and then measured by flow cytometry. RESULTS: Higher-level TMPs (total
      microparticles) and PMPs, but lower-level RMPs, LMPs, and MMPs were detected in
      fresh PLTs on the day of collection compared with those before collection. During
      storage, TMP, PMP, and RMP counts were significantly higher on Day 3 and Day 5,
      but MMP and LMP counts were only marginally higher on Day 3 in PLT supernatants.
      There were no significant differences in MP levels in PLTs with or without
      leukofiltration. CONCLUSION: MP formation was affected by the apheresis
      procedure. RMPs, LMPs and MMPs were lower after PLT apheresis. During storage,
      TMPs, PMPs, RMPs, LMPs, and MMPs were found to be higher in PLT supernatants.
      Leukofiltration exerted no significant effect on all MPs in PLT products.

PMID- 30203554
TI  - The role of social media for blood donor motivation and recruitment.
AB  - BACKGROUND: Social media platforms have become an important lifestyle aspect.
      Therefore, we implemented communication via social media platforms to recruit new
      donors and to motivate repeat donors. Here, we report a survey among donors of
      our blood donation facility to evaluate the impact of different strategies for
      donor motivation from the donors' perspective. STUDY DESIGN AND METHODS: During 8
      consecutive weeks, all whole blood donors were asked to participate. The survey
      consisted of a questionnaire including the demographic items sex, age, number of
      prior donations, and 14 potential motivators for blood donation. Social media
      included the items "Facebook" and "Jodel" (German local mobile application).
      RESULTS: Of 3320 consecutive donors, 2920 (88%) participated in the survey.
      Social media motivated 7.4% of our donors, among them mainly young and female
      donors. For first-time donors (FTDs; n = 157) the three strongest motivational
      factors were friends and/or relatives (73%), social media (15%), and "I do not
      need additional motivation" (11%). Repeat donors (n = 2693) most often stated
      that they do not need additional motivation (72%) and only 7% were motivated by
      social media. CONCLUSION: Social media have become the second most important
      motivator to recruit FTDs beside relatives and friends who are by far the main
      motivators for FTDs. For repeat donors, social media play a less important role.
      Social media are becoming increasingly important for transfusion services.

PMID- 30203555
TI  - 2,4-D-induced parthenocarpy in pear is mediated by enhancement of GA4
      biosynthesis.
AB  - Parthenocarpy, the productions of seedless fruit without pollination or
      fertilization, is a potentially desirable trait in many commercially grown
      fruits, especially in pear, which is self-incompatible. Phytohormones play
      important roles in fruit set, a process crucial for parthenocarpy. In this study,
      2,4-dichlorophenoxyacetic acid (2,4-D), an artificially synthesized plant growth
      regulator with functions similar to auxin, was found to induce parthenocarpy in
      pear. Histological observations revealed that 2,4-D promoted cell division and
      expansion, which increased cortex thickness, but the effect was weakened by
      paclobutrazol (PAC), a gibberellin (GA) biosynthesis inhibitor. Phenotypic
      differences in pear may therefore be due to different GA contents. Hormone
      testing indicated that 2,4-D mainly induced the production of bioactive GA4 ,
      rather than GA3. Three key oxidase genes function in the GA biosynthetic pathway:
      GA20ox, GA3ox and GA2ox. In a pear group treated with only 2,4-D, PbGA20ox2-like
      and PbGA3ox-1 were significantly upregulated. When treated with 2,4-D
      supplemented with PAC, however, expression levels of these genes were
      significantly downregulated. Additionally, PbGA2ox1-like and PbGA2ox2-like
      expression levels were significantly downregulated in pear treated with either
      2,4-D only or 2,4-D supplemented with PAC. We thus hypothesize that 2,4-D can
      induce parthenocarpy by enhancing GA4 biosynthesis.

PMID- 30203556
TI  - Health-related quality of life of adolescents with type 1 diabetes in the context
      of resilience.
AB  - BACKGROUND: Adolescents with type 1 diabetes (T1D) can be faced with
      deterioration in glycemic control (GC), reduced health-related quality of life
      (HRQoL), and other psychosocial problems. It is important to understand how the
      disease and its clinical conditions influence HRQoL and how adolescents are able
      to overcome the life adjustment difficulties. OBJECTIVE: To assess HRQoL of
      adolescents with T1D from demographic, clinical, personal, and behavioral point
      of view. SUBJECTS: A total of 229 adolescents with T1D (51.2% males) with a mean
      age of 15.35 (2.29) years old were recruited from three diabetes centers. The
      mean diabetes duration was 7.48 (3.87), the mean hemoglobin A1C (HbA1c) level was
      10.3 (1.76) mmol/L. METHODS: A multicenter quantitative correlational design
      study was applied to investigate the influence of sex, age, diabetes duration, GC
      expressed by HbA1c, intensive insulin regimen, physical activity (PA), resilience
      (RS), and socioeconomic background on HRQoL. RESULTS: Presence of the diabetes
      symptoms and worry about the disease has negative impact on the patients' HRQoL.
      Stepwise multiple regression analyses indicated that insulin pump therapy, male
      sex, and higher level of RS were significantly related to an increase in HRQoL,
      whereas the higher level of PA, male sex, and better HRQoL was significantly
      related to positive change in RS. Patients treated with insulin pump therapy had
      significantly better HRQoL. CONCLUSIONS: Significant association can be observed
      between HRQoL and RS. Supposedly, higher level of PA promotes higher level of RS
      that in turn helps increase HRQoL in adolescents with T1D. Treatment with insulin
      pump therapy also promotes better HRQoL.

PMID- 30203557
TI  - Annual report of the Women's Health Care Committee, Japan Society of Obstetrics
      and Gynecology, 2018.
AB  - Since 2010, the Women's Health Care Committee has addressed important issues
      linked to women's quality of life. The five agendas this committee has engaged
      this academic year are: (i) clinical study of urinary complications in perinatal
      and postpartum women's health care; (ii) education on infectious diseases
      prophylaxis in obstetrics and gynecology in Japan; (iii) educational activities
      regarding management guidelines for a female athlete's health care; (iv) training
      program for women's healthcare advisers; and (v) pregnancy- and lactation
      associated osteoporosis (PLOP). The detailed activities of the five subcommittees
      are described herein. This report is based on the Japanese version of our annual
      report (Acta Obst Gynaec Jpn 2018; 70: 1538-1546), which publicizes the
      activities of our committee.

PMID- 30203558
TI  - The sickle cell disease implementation consortium: Translating evidence-based
      guidelines into practice for sickle cell disease.

PMID- 30203560
TI  - Terminology report from the International Continence Society (ICS) Working Group
      on Underactive Bladder (UAB).

PMID- 30203559
TI  - Inflammatory cytokines tumour necrosis factor-alpha and interleukin-8 enhance
      airway smooth muscle contraction by increasing L-type Ca2+ channel expression.
AB  - Inflammation elevates intracellular calcium concentrations ([Ca2+ ]i ) in airway
      smooth muscle (ASM). The L-type Ca2+ channel (L-VDCC) plays an important role in
      regulating Ca2+ influx in ASM. However, the role of L-VDCC in the inflammatory
      cytokine-induced pathology of ASM remains unclear. In the present study, we used
      calcium imaging and isometric tension measurements to assess the role of L-VDCC
      in agonist-induced [Ca2+ ]i rise and the associated contractions in mouse ASM,
      and we used immunoblotting to identify L-VDCC protein expression levels in mouse
      ASM after exposure to tumour necrosis factor alpha (TNF-alpha) or interleukin-8
      (IL-8). Our results showed that high-K+ - or carbachol-induced contractions of
      mouse ASM were significantly greater after pretreatment with TNF-alpha or IL-8
      for 24 hours. Both verapamil and nifedipine, L-VDCC inhibitors, abolished this
      increased contraction induced by TNF-alpha or IL-8 pretreatment. Moreover, TNF
      alpha treatment enhanced carbachol-induced Ca2+ influx in ASM cells, and this
      effect was abrogated by verapamil. Additionally, immunoblotting results showed
      that preincubation of mouse ASM with TNF-alpha or IL-8 also enhanced L-VDCC
      protein expression. On the basis of these findings, we concluded that
      proinflammatory cytokines, such as TNF-alpha and IL-8, increase the expression
      level of L-VDCC, which in turn contributes to augmented agonist-induced ASM
      contractions. This effect of inflammation on L-VDCC expression in ASM may be
      associated with airway hyper-responsiveness and involved in the development of
      asthma.

PMID- 30203561
TI  - Mesoporous Bioactive Glasses Equipped with Stimuli-Responsive Molecular Gates for
      Controlled Delivery of Levofloxacin against Bacteria.
AB  - An increase of bone diseases incidence has boosted the study of ceramic
      biomaterials as potential osteo-inductive scaffolds. In particular, mesoporous
      bioactive glasses have demonstrated to possess a broad application in the bone
      regeneration field, due their osteo-regenerative capability and their ability to
      release drugs from the mesoporous structure. These special features have been
      studied as an option to fight against bone infection, which is one of the most
      common problems regarding bone regeneration therapies. In this work, a mesoporous
      bioglass functionalized with polyamines and capped with adenosine triphosphate
      (ATP) as the molecular gate was developed for the controlled release of the
      antibiotic levofloxacin. Phosphate bonds of ATP were hydrolyzed in the presence
      of acid phosphatase (APase), the concentration of which is significantly
      increased in bone infection due to the activation of bone resorption processes.
      The solid was characterized and tested successfully against bacteria. The final
      gated solid induced bacterial death only in the presence of acid phosphatase.
      Additionally, it was demonstrated that the solid is not toxic against human
      cells. The double function of the prepared material as a drug delivery system and
      bone regeneration enhancer confirms the possible development of a new approach in
      the tissue engineering field, in which controlled release of therapeutic agents
      can be finely tuned and, at the same time, osteoinduction is favored.

PMID- 30203562
TI  - Optic nerve head perfusion changes preceding peripapillary retinal nerve fibre
      layer thinning in preclinical diabetic retinopathy.
AB  - IMPORTANCE: Whether neural or vascular defects occur first in the early onset of
      diabetic retinopathy (DR) is undetermined. BACKGROUND: To investigate
      microcirculation and microstructure differences of optic nerve head (ONH) between
      diabetic eyes without clinically evident retinopathy and healthy controls using
      optical coherence tomography angiography (OCTA). DESIGN: Cross-sectional
      observational study. PARTICIPANTS: Sixty eyes of 60 patients with type 2 diabetes
      and without clinically evident retinopathy and 60 eyes of 60 age-matched healthy
      controls were included in this study. METHODS: All participants underwent 4.5 *
      4.5-mm rectangle scans centred on the ONH using OCTA (RTVue-XR Avanti; Optovue,
      Fremont, CA). MAIN OUTCOME MEASURES: Peripapillary retinal nerve fibre layer
      (RNFL) thickness and capillary perfusion density inside the ONH and in the
      peripapillary region were compared between the two groups. RESULTS: Vessel
      density values in both peripapillary and inside the disc were significantly lower
      in diabetic patients without DR compared to normal controls. The reduction of
      vessel density was prominent in all eight peripapillary sectors in diabetic eyes
      (all P < 0.05). Thinning of RNFL thickness was significant in the nasal superior
      (P < 0.001), inferior nasal (P = 0.023) and superior nasal quadrant (P < 0.001)
      in diabetic eyes in comparison to normal controls. CONCLUSIONS AND RELEVANCE: ONH
      perfusion and peripapillary RNFL thickness were significantly decreased in
      preclinical DR patients compared to normal controls. Microvascular alterations in
      ONH may occur earlier than peripapillary RNFL defect in the course of DR.

PMID- 30203563
TI  - Molecular genetic study of glutaric aciduria, type I: Identification of a novel
      mutation.
AB  - Glutaric acidemia type I (GA-1) is an inborn error of metabolism due to
      deficiency of glutaryl-CoA dehydrogenase (GCDH), which catalyzes the conversion
      of glutaryl-CoA to crotonyl-CoA. GA-1 occurs in about 1 in 100 000 infants
      worldwide. The GCDH gene is on human chromosome 19p13.2, spans about 7 kb and
      comprises 11 exons and 10 introns. Tandem mass spectrometry (MS/MS) was used for
      clinical diagnosis in a proband from Iran with GA-1. Sanger sequencing was
      performed using primers specific for coding exons and exon-intron flanking
      regions of the GCDH gene in the proband. Cosegregation analysis and in silico
      assessment were performed to confirm the pathogenicity of the candidate variant.
      A novel homozygous missense variant c.1147C > A (p.Arg383Ser) in exon 11 of GCDH
      was identified. Examination of variant through in silico software tools
      determines its deleterious effect on protein in terms of function and stability.
      The variant cosegregates with the disease in family. In this study, the clinical
      and molecular aspects of GA-1 were investigated, which showed one novel mutation
      in the GCDH gene in an Iranian patient. The variant is categorized as pathogenic
      according to the the guideline of the American College of Medical Genetics and
      Genomics (ACMG) for variant interpretation. This mutation c.1147C > A
      (p.Arg383Ser) may also be prevalent among Iranian populations.

PMID- 30203564
TI  - PlGF knockdown induced apoptosis through Wnt signaling pathway in gastric cancer
      stem cells.
AB  - Despite the fact that much research has focused on gastric cancer, it is still a
      worldwide concern, because of the difficulties with factors such as signaling
      pathway crosstalk and gastric cancer stem cell (GCSC). Placental growth factor
      (PlGF) is one of these factors, and its tumorigenicity potential still remains a
      question. As a result, we have investigated the effect of PlGF knockdown on
      apoptosis and genes involved in the Wnt signaling pathway, and apoptosis in
      cancer stem cells derived from AGS an MKN-45 gastric cancer cell lines. We
      isolated GCSCs from MKN-45 and AGS cell lines on a nonadherent surface. Then the
      cell viability, the real-time reverse transcription-polymerase chain reaction
      data of the genes involved in the Wnt signaling pathway, and apoptosis were
      evaluated. Furthermore, DNA laddering was used to show the apoptotic effect and
      DNA fragmentation caused by the PlGF knockdown. Our investigation revealed that
      the PlGF knockdown with PlGF-specific small interfering RNA at 40 pmol for GCSCs
      derived from MKN-45 and AGS at 24 hours can significantly affect the cell
      viability, the Wnt signaling pathway, and the apoptosis-related genes expression.
      In conclusion, we showed the PlGF knockdown may induce apoptosis via the Wnt
      signaling pathway in GCSCs.

PMID- 30203565
TI  - Transcriptomic analysis of epigenetic modification genes in the termite
      Reticulitermes speratus.
AB  - Eusocial insects display a caste system in which different castes are
      morphologically and physiologically specialized for different tasks. Recent
      studies have revealed that epigenetic modifications, including DNA methylation
      and histone modification, mediate caste determination and differentiation,
      longevity, and polyethism in eusocial insects. Although there has been a growing
      interest in the relationship between epigenetic mechanisms and phenotypic
      plasticity in termites, there is little information about differential expression
      levels among castes and expression sites for these genes in termites. Here we
      show royal-tissue-specific expression of epigenetic modification genes in the
      termite Reticulitermes speratus. Using RNA-seq, we identified 74 genes, including
      three DNA methyltransferases, seven sirtuins, 48 Trithorax group proteins, and 16
      Polycomb group proteins. Among these genes, 15 showed king-specific expression,
      and 52 showed age-dependent differential expression in kings and queens.
      Quantitative real-time PCR revealed that DNA methyltransferase 3 is expressed
      specifically in the king's testis and fat body, whereas some histone modification
      genes are remarkably expressed in the king's testis and queen's ovary. These
      findings imply that epigenetic modification plays important roles in the gamete
      production process in termite kings and queens.

PMID- 30203566
TI  - Can pain assessment tools accurately measure pain experience of disabled
      individuals?

PMID- 30203567
TI  - Growth of Epithelial Organoids in a Defined Hydrogel.
AB  - Epithelial organoids are simplified models of organs grown in vitro from
      embryonic and adult stem cells. They are widely used to study organ development
      and disease, and enable drug screening in patient-derived primary tissues.
      Current protocols, however, rely on animal- and tumor-derived basement membrane
      extract (BME) as a 3D scaffold, which limits possible applications in
      regenerative medicine. This prompted us to study how organoids interact with
      their matrix, and to develop a well-defined hydrogel that supports organoid
      generation and growth. It is found that soft fibrin matrices provide suitable
      physical support, and that naturally occurring Arg-Gly-Asp (RGD) adhesion domains
      on the scaffold, as well as supplementation with laminin-111, are key parameters
      required for robust organoid formation and expansion. The possibility to
      functionalize fibrin via factor XIII-mediated anchoring also allows to covalently
      link fluorescent nanoparticles to the matrix for 3D traction force microscopy.
      These measurements suggest that the morphogenesis of budding intestinal organoids
      results from internal pressure combined with higher cell contractility in the
      regions containing differentiated cells compared to the regions containing stem
      cells. Since the fibrin/laminin matrix supports long-term expansion of all tested
      murine and human epithelial organoids, this hydrogel can be widely used as a
      defined equivalent to BME.

PMID- 30203568
TI  - Avoiding inappropriate therapy of single-lead implantable cardioverter
      defibrillator by using atrial-sensing electrodes.
AB  - INTRODUCTION: The single-chamber implantable cardioverter-defibrillator (ICD) can
      be associated with more frequent inappropriate therapies compared with dual
      chamber ICDs, when they are accompanied by a simpler implantation procedure. The
      aim of this study was to investigate whether the use of a single-lead ICD system
      with atrial-sensing electrodes results in a reduction of inappropriate ICD
      therapy. METHODS AND RESULTS: The study population consisted of 212 consecutive
      patients, who underwent primary prophylactic single-lead ICD implantation at our
      institute. A ventricular lead with atrial-sensing electrodes was implanted in 77
      patients (36%; Group-VDD) and a ventricular lead without atrial-sensing
      electrodes was implanted in 135 patients (64%; Group-VVI). Procedural and follow
      up data were collected in a prospective registry. A higher prevalence of atrial
      fibrillation was present in Group-VDD. There were no other significant
      differences in patient baseline characteristics (age, sex, and other
      comorbidities) or follow-up period between the two groups. The operative
      parameters including fluoroscopic burden showed no significant differences
      between Group-VDD and Group-VVI. During a mean follow-up period of 697 +/- 392
      days, 26 patients (12%) experienced appropriate ICD therapies and 13 patients
      (6%) suffered inappropriate ICD therapies. The incidence of inappropriate ICD
      therapies in Group-VDD was significantly lower as compared to that of Group-VVI
      (1/77 [1%] vs 12/135 [9%]; log-rank, P = 0.028). The incidence of appropriate ICD
      therapies and the occurrence of device-related complications showed no
      significant difference between the two groups. CONCLUSION: Single-lead ICD with
      atrial-sensing electrodes shows a lower incidence of inappropriate ICD therapy
      compared with the absence of atrial-sensing electrodes, without additional
      operative burden or increased complications.

PMID- 30203569
TI  - Embryo timelapses can be compiled and quantified to understand canonical histone
      dynamics across multiple cell cycles.
AB  - In the last decade, computational processing of big datasets has facilitated the
      analyses of unprecedented quantities of biological data. Thus, automation and big
      data analysis have been revolutionary in detecting and quantifying subtle
      phenotypes in cell biological contexts. Analyzing similar quantities of data in
      larger and more complicated biological systems such as developing embryos has
      been more challenging due to experimental limitations on both ensemble data
      collection and analysis. These challenges include photosensitivity of living
      samples and of the fluorescently tagged proteins under study, collectively
      limiting the number of images that can be acquired in a single timelapse series.
      Here we present a streamlined workflow to quantify dynamics of fluorescently
      labeled proteins over the course of several cell cycles in early embryos, taking
      advantage of the stereotypical nature of early development that is inherent for
      many organisms. We benchmark this pipeline studying a fluorescently labeled
      histone during early embryonic development of the nematode Caenorhabditis
      elegans. Our strategy allowed us to overcome biological and experimental
      variation among our timelapse series and quantify nuclear accumulation rate,
      chromatin incorporation, and turnover/stability of canonical histones. We find
      that histone proteins are broadly stable in early C. elegans development. Thus,
      changes in genome regulation occurring in early development do not manifest in
      gross changes in histone metabolism. Our method enabling characterization of
      cumulative protein dynamics over several cell cycles of developmental time with
      high temporal resolution can be applied to expand our understanding of diverse
      cellular and developmental processes.

PMID- 30203570
TI  - Impact of Fabp1 Gene Ablation on Uptake and Degradation of Endocannabinoids in
      Mouse Hepatocytes.
AB  - Liver fatty-acid-binding protein (FABP1, L-FABP) is the major cytosolic
      binding/chaperone protein for both precursor arachidonic acid (ARA) and the
      endocannabinoid (EC) products N-arachidonoylethanolamine (AEA) and 2
      arachidonoylglycerol (2-AG). Although FABP1 regulates hepatic uptake and
      metabolism of ARA, almost nothing is known regarding FABP1's impact on AEA and 2
      AG uptake, intracellular distribution, and targeting of AEA and 2-AG to
      degradative hepatic enzymes. In vitro assays revealed that FABP1 considerably
      enhanced monoacylglycerol lipase hydrolysis of 2-AG but only modestly enhanced
      AEA hydrolysis by fatty-acid amide hydrolase. Conversely, liquid chromatography
      mass spectrometry of lipids from Fabp1 gene-ablated (LKO) hepatocytes confirmed
      that loss of FABP1 markedly diminished hydrolysis of 2-AG. Furthermore, the real
      time imaging of novel fluorescent NBD-labeled probes (NBD-AEA, NBD-2-AG, and NBD
      ARA) resolved FABP1's impact on uptake vs intracellular targeting/hydrolysis.
      FABP1 bound NBD-ARA with 2:1 stoichiometry analogous to ARA, but bound NBD-2-AG
      and NBD-AEA with 1:1 stoichiometry-apparently at different sites in FABP1's
      binding cavity. All three probes were taken up, but NBD-2-AG and NBD-AEA were
      targeted to lipid droplets. LKO reduced the uptake of NBD-ARA as expected,
      significantly enhanced that of NBD-AEA, but had little effect on NBD-2-AG. These
      data indicated that FABP1 impacts hepatocyte EC levels by binding EC and
      differentially impacts their intracellular hydrolysis (2-AG) and uptake (AEA).

PMID- 30203571
TI  - KMT2A (MLL) rearrangements observed in pediatric/young adult T-lymphoblastic
      leukemia/lymphoma: A 10-year review from a single cytogenetic laboratory.
AB  - T-lymphoblastic leukemia/lymphoma (T-ALL/LBL) accounts for approximately 15% of
      pediatric and 25% of adult ALL. While the underlying frequency of KMT2A (MLL)
      gene rearrangements has been identified in approximately 4-8% of T-ALL/LBL cases,
      a paucity of literature is available to characterize further the KMT2A
      rearrangements in pediatric/young adult T-ALL/LBL. A 10-year retrospective review
      was performed to identify KMT2A rearrangements in specimens sent for T-ALL/LBL
      fluorescence in situ hybridization studies in patients under the age of 30 years.
      Of 806 T-ALL/LBL FISH studies performed on unique individuals, 27 (3.3%) harbored
      KMT2A rearrangements. Nineteen patients were male and eight were female (M:F
      ratio, 2.4:1) with ages ranging from 1 to 20 years (mean 12, median 12). Of the
      27 cases, nine (33%) had KMT2A/MLLT1 fusions, eight (30%) had KMT2A/AFDN fusions,
      two (7%) had KMT2A/ELL fusions, and one (4%) had a KMT2A/MLLT10 fusion. In
      addition, five (19%) had KMT2A rearrangements with unidentified gene fusion
      partners and two (7%) had 3'KMT2A deletions. Our results indicate that MLLT1 and
      AFDN account for the majority (63%) of KMT2A gene partners in pediatric/young
      adult T-ALL/LBL, while no KMT2A/AFF1 or KMT2A/MLLT3 fusions were observed despite
      their common identification in B-ALL and acute myeloid leukemia, respectively. In
      addition to diagnostic and prognostic value, detecting specific KMT2A fusions may
      also be of clinical importance in the era of targeted therapies.

PMID- 30203572
TI  - When women work: Endocrine reactivity in women during everyday physical activity
      at high altitude.
AB  - OBJECTIVES: This study explores the acute endocrine reactivity of testosterone
      and cortisol in women engaging in everyday physical activity in a high altitude
      environment. METHODS: Data were collected from 35 women living in the Himalayas,
      with women recruited from both high (>10 000 ft.) and low altitude villages (<10
      000 ft.). Saliva samples were collected at 3 time points (pre-activity, 30 and 60
      minutes) and women wore the wGT3X-BT Actigraph during an hour of everyday work to
      assess the relationship between high altitude, endocrine reactivity, and physical
      activity. Saliva samples were then analyzed for testosterone and cortisol.
      RESULTS: Women living at high altitude had lower cortisol and testosterone
      levels, after controlling for moderate-to-vigorous physical activity, age, and
      sum of skinfolds. CONCLUSIONS: Testosterone and cortisol increase allocation of
      energy to costly somatic tissues and the utilization of stored energy. Lower
      production of these hormones may be beneficial for heightened energetic demands
      at high altitude.

PMID- 30203574
TI  - A case study exploring the effectiveness of an innovative "5Q Care Test" to
      determine whether patients with complex needs require health or social care.
AB  - A case study was conducted in 2016 to evaluate the effectiveness of an innovation
      to enable people with "complex" care requirements to be discharged from hospital
      to an appropriate service for their care, without using the NHS England
      Continuing Health Care (CHC) assessment. The setting was a rural district general
      hospital in England, where the quality outcomes and cost-effectiveness of the CHC
      assessment being conducted in hospital were giving cause for concern. The NHS CHC
      Framework advocates conducting these assessments in the community where a more
      accurate indication of long-term care can be determined. The "5Q Care Test" was
      collaboratively developed with health and social care partners, care providers,
      and CHC interest groups, including users of the services. It was implemented as a
      tool to support moving the CHC assessment into the community, as it enabled
      practitioners to swiftly determine patients' appropriate initial care pathway out
      of hospital. A full economic impact analysis was conducted 7 months after the
      tool was introduced. The results showed significant improvement in the quality
      and cost-effectiveness of the "5Q Care Test," with a reduction in the hospital
      length of stay, which is known to be associated with improved outcomes for
      patients and financial savings.

PMID- 30203573
TI  - In Situ Thermal Atomization To Convert Supported Nickel Nanoparticles into
      Surface-Bound Nickel Single-Atom Catalysts.
AB  - The arrangement of the active sites on the surface of a catalysts can reduce the
      problem of mass transfer and enhance the atom economy. Herein, supported Ni metal
      nanoparticles can be transformed to thermal stable Ni single atoms, mostly
      located on the surface of the support. Assisted by N-doped carbon with abundant
      defects, this synthetic process not only transform the nanoparticles to single
      atoms, but also creates numerous pores to facilitate the contact of dissolved CO2
      and single Ni sites. The proposed mechanism is that the Ni nanoparticles could
      break surface C-C bonds drill into the carbon matrix, leaving pores on the
      surface. When Ni nanoparticles are exposed to N-doped carbon, the strong
      coordination splits Ni atoms from Ni NPs. The Ni atoms are stabilized within the
      surface of carbon substrate. The continuous loss of atomic Ni species from the
      NPs would finally result in atomization of Ni NPs. CO2 electroreduction testing
      shows that the surface enriched with Ni single atoms delivers better performance
      than supported Ni NPs and other similar catalysts.

PMID- 30203575
TI  - Anti-inflammatory and antiradical effects of a 2% diosmin cream in a human skin
      organ culture as model.
AB  - BACKGROUND: Diosmin, a naturally occurring flavonoid, is considered as a vascular
      protective agent and is used orally to treat chronic venous insufficiency. It
      exhibits anti-inflammatory and free radical scavenging properties, but, like many
      other flavonoids, it is poorly absorbed in the small intestine. OBJECTIVE: Our
      aim was to investigate the skin protective effects of a diosmin-based cream,
      using skin organ culture as model. METHODS: Fragments of human skin explants,
      cultured ex vivo, were allocated to four treatment groups: no cream, no cream +
      stress, placebo cream + stress, and 2% diosmin cream + stress. Stress was induced
      by exposure to either substance P (anti-inflammatory effects' assessment) or UVB
      irradiation (free radical scavenging effects' assessment). Vascular dilation and
      the pro-inflammatory mediator IL-8 release were determined in the first model,
      whereas hydrogen peroxide level and the number of cyclobutane pyrimidine-positive
      cells were evaluated in the second model. RESULTS: In the substance P-induced
      inflammation model, 2% diosmin cream exhibited significant vasoconstrictive
      (proportion of dilated capillaries: -29%, capillary luminal area: -49% vs no
      cream + stress) and anti-inflammatory (IL-8 release: -36% vs no cream + stress)
      effects. In the UVB irradiation model, 2% diosmin cream significantly reduced
      hydrogen peroxide production and cyclobutane pyrimidine dimer formation (-45% and
      -36% vs no cream + stress, respectively). These effects were not observed with
      placebo cream. CONCLUSION: Diosmin administered topically may protect skin
      against the biological effects of various exogenous or endogenous stresses, such
      as those involved in chronic venous disease.

PMID- 30203576
TI  - Association between 14 bp insertion/deletion HLA-G functional polymorphism and
      insulin resistance in a cohort of Italian children with obesity.
AB  - BACKGROUND: The non-classical HLA-class I molecule-g (HLA-G) gene shows a
      deletion/insertion (del/ins) polymorphism of a 14-base-pair sequence (14 bp) in
      the exon 8 at the 3' untranslated region. The presence of the 14 bp insertion
      allele has been associated to lower soluble HLA-G protein production, a protein
      with anti-inflammatory activities. So far, no studies have investigated the
      relationship between HLA-G 14 bp del/ins polymorphism and metabolic features of
      obese children and adolescents. We aimed to assess if the HLA-G ins/del
      polymorphism, and in particular the HLA-G ins/ins genotype determining lower sHLA
      G production, is associated to insulin resistance (evaluated by homeostasis model
      assessment [HOMA]) in a population of obese children. METHODS: We enrolled 574
      obese children and adolescents. Anthropometric and laboratory data were
      collected. The white blood cell (WBC) count was evaluated as surrogate marker of
      inflammation. C-reactive protein (CRP) was available in 48 patients. HOMA was
      calculated. Patients were genotyped for the HLA-G del/ins polymorphism. RESULTS:
      Subjects carrying the HLA-G ins/ins genotype, presented with higher HOMA, WBC and
      CRP values, compared to del/ins and del/del genotypes (P <= 0.0009, <=0.02 and
      <=0.0001, respectively). Comparison of the regression line slopes, performed for
      HOMA and WBC on the basis of HLA-G genotypes, showed that subjects carrying the
      HLA-G ins/ins genotype presented with a stronger correlation between HOMA and
      WBC, compared to the other genotypes (Model r2 3.13%, P <= 0.006). CONCLUSIONS:
      We showed a strong association between HLA-G 14 bp ins/ins genotype and HOMA in
      obese children and adolescents. This association could be hypothetically
      modulated by subclinical inflammation.

PMID- 30203577
TI  - Modulation of immune response to induced-arthritis by low-level laser therapy.
AB  - As low-level laser therapy immune cells responses are not always clarified, this
      study aimed to evaluate cytokines and immune cells profile after low-level laser
      therapy (LLLT) on arthritis-induced model. Arthritis was induced in C57BL/6 mice
      divided into five groups: euthanized 5 hours after inflammation induction;
      untreated; dexamethasone treated; LLLT at 3 Jcm-2 ; LLLT at 30 Jcm-2 . Cytokine
      measurements by enzyme-linked immunosorbent assay and mRNA cytokine relative
      levels by real-time quantitative polymerase chain reaction were performed with
      arthritic ankle (IL-1beta, IL-6, TNF-alpha, IL-10 and TGF-beta). Macrophages,
      dendritic cells, natural killer cells, lymphocytes CD4+ , CD8+ , Treg and
      costimulatory proteins were quantified in proximal lymph node by flow cytometry.
      Data showed decrease in all cytokine levels after LLLT and alteration in mRNA
      relative levels, depending on the energy density used. LLLT was able to increase
      of immune cell populations analyzed in the lymph node as well as costimulatory
      proteins expression on macrophages and dendritic cells. Treg TCD4+ and TCD8+
      population enrichment was observed in LLLT at 3 and 30 Jcm-2 groups,
      respectively. Furthermore, Treg TCD8+ cells expressing higher levels of CD25 were
      observed at LLLT at 30 Jcm-2 group. Our results indicate that LLLT could change
      the inflammatory course of arthritis, tending to accelerate its resolution
      through immune cells photobiostimulation.

PMID- 30203578
TI  - Microarray-based analysis of whole-genome DNA methylation profiling in early
      detection of breast cancer.
AB  - Emerging evidence indicated that changes in DNA methylation early in breast
      cancer (BC) development might be clinically relevant for therapeutic decisions.
      Through analysis of whole-genome gene expression microarray and DNA methylation
      microarray, we explored genes with abnormal DNA methylation in BC for early
      detection. Firstly, human BC tissues and adjacent non-cancerous tissues were
      collected from nine BC patients. Gene expression microarray sequencing was
      conducted for identifying differentially expressed genes and DNA methylation
      microarray sequencing for differentially methylated genes in BC. Differentially
      expressed genes and methylated genes in BC were further explored using the Cancer
      Genome Atlas database. The correlation between DNA methylation and gene
      expression was illustrated by multiple comparisons. In other 60 clinical samples,
      methylation specific polymerase chain reaction (PCR) and reverse transcription
      quantitative PCR were applied for the methylation of HOXA4 and IGF1 genes in BC
      and adjacent non-cancerous tissues. In total, 1680 upregulated genes and 1249
      downregulated genes were determined in BC. Chromosome 16 and 17 showed more
      differentially methylated genes, and DNA methylation level was increased in BC
      tissues in each gene region. Chromosome 19 showed more differentially methylated
      genes, and DNA methylation level was increased in BC tissues in the exoniensis 1,
      untranslated region-5 and transcriptional start site 200 gene regions. In other
      60 clinical samples, HOXA4 and IGF1 in BC tissues presented increased DNA
      methylation and decreased gene expression in BC. MCF7 cells treated with RG108
      showed decreased HOXA4 and IGF1 expressions. It was estimated that HOXA4 and IGF1
      were identified with increased DNA methylation and decreased gene expression in
      BC, which may serve as biomarkers in early BC detection.

PMID- 30203579
TI  - Minimally invasive approaches to axillary osmidrosis treatment: A comparison
      between superficial liposuction with automatic shaver curettage, subcutaneous
      laser treatment, and microwave-based therapy with a modified technique.
AB  - BACKGROUND: Minimally invasive techniques, including superficial liposuction with
      automatic shaver curettage (LC), subcutaneous laser treatment, and microwave
      based therapy have been developed to treat osmidrosis. Few studies have compared
      these three techniques in relation to clinical efficacy, life quality
      improvement, and downtime. AIMS: We aim to evaluate clinical results and life
      quality improvement, in addition to downtime and complications, between these
      three techniques. PATIENTS/METHODS: Clinical records of patients treated with
      these three minimally invasive techniques for axillary osmidrosis were
      retrospectively reviewed. Hyperhidrosis disease severity scale, Dermatology Life
      of Quality Index, clinical improvement, complication, and recurrence were
      assessed. RESULTS: Among 403 patients, 168 received microwave-based therapy, 119
      received subcutaneous laser treatment, and 116 received LC. All treatments showed
      significant improvements (P < 0.001) in HDSS, DLQI and clinical result after 3
      and 12 months comparing to the baseline. But the improvements of subcutaneous
      laser were significantly inferior to microwave-base therapy and LC. Patients who
      received LC had a significantly longer downtime (P < 0.001) than those who
      received other treatments. The recurrence rate was significantly higher in the
      subcutaneous laser treatment group, and the microwave-based therapy group
      exhibited a longer recurrence duration (P < 0.001). LC group presented higher
      complication rate than other treatments. CONCLUSION: Comparing to other
      treatments, microwave-based therapy was effective in treating osmidrosis with
      minimal downtime, recurrence, and complications. It could be a durable and
      effective therapeutic modality for osmidrosis and is less operator-dependent. It
      may be considered as a first-line treatment for axillary osmidrosis.

PMID- 30203580
TI  - The association of basal insulin treatment versus standard care with outcomes in
      anti-GAD positive and negative subjects: A post-hoc analysis of the ORIGIN trial.
AB  - We compared cardiovascular and other outcomes in patients with dysglycaemia with
      or without anti-glutamic acid dehydrogenase (GAD) antibodies participating in the
      Outcome Reduction with Initial Glargine Intervention (ORIGIN) trial. Of the 12
      537 participants, 8162 had anti-GAD measured at baseline and 267 were anti-GAD
      positive. The effects of insulin glargine versus standard care and of n-3 fatty
      acids supplements versus placebo were compared by testing the interaction of the
      treatment effects and anti-GAD status. The effect of glargine on development of
      new diabetes was assessed in participants without previous diabetes at baseline.
      The overall incidence of outcomes did not differ between anti-GAD positive and
      anti-GAD negative subjects. The incidence of the composite of cardiovascular
      death, non-fatal myocardial infarction, or non-fatal stroke did not differ
      between anti-GAD positive participants randomized to insulin glargine or to
      standard care, with a hazard ratio (HR) (95% confidence interval [CI]) of 0.80
      (0.44-1.44) or in anti-GAD negative participants with a HR of 1.07 (0.96-1.20) (P
      for interaction = 0.20).

PMID- 30203581
TI  - External quality assessment of p210 BCR-ABL1 transcript quantification by RT
      qPCR: Findings and recommendations.
AB  - INTRODUCTION: External quality assessment (EQA) is an essential tool for quality
      assurance of analytical testing processes of p210 BCR-ABL1 transcripts by RT
      qPCR. As an EQA provider, the National Center for Clinical Laboratories organized
      an EQA scheme of p210 BCR-ABL1 testing in China for the first time to identify
      existing problems and ensure the reliability of p210 BCR-ABL1 testing. METHODS:
      Using armored RNA technology, we first constructed pACYC-MS2-p210 and CG
      recombinant plasmids and expressed p210 and CG armored RNAs, with packaging
      segments of p210 BCR-ABL1 fusion gene (FG) and four common control gene (CG)
      transcripts. Using these armored RNAs, we prepared lyophilized p210 quality
      control (QC) sample panels and evaluated detection performance of participating
      laboratories in China. RESULTS: Of the 66 participating laboratories, great
      variation was found with coefficient of variation (CV%) of raw p210 BCR-ABL1
      results basically ranging from 60.0% to 100.0%. In 24 International Scale (IS)
      laboratories, the CV% of results decreased from 82.4% to 61.6%, and the
      percentage of laboratories within 2-, 3-, and 5-fold of the median values
      increased from 78.2%, 87.0%, and 92.1% to 80.1%, 89.4%, and 97.2%, respectively,
      after conversion with a laboratory-specific conversion factor (CF); however,
      poorly converted results were also observed in laboratories resulting from
      changed components of RT-qPCR procedures. False-negative and false-positive
      results were also found in the EQA. CONCLUSIONS: Various problems were found for
      p210 BCR-ABL1 detection in the EQA. By solving the existing problems, the
      performance of p210 BCR-ABL1 detection can be improved, ensuring robust
      laboratory diagnostic capacities in China.

PMID- 30203582
TI  - Pathogenesis of Helicobacter pylori infection.
AB  - In this review, we highlight progress in the last year in characterizing known
      virulence factors like flagella and the Cag type IV secretion system with
      sophisticated structural and biochemical approaches to yield new insight on the
      assembly and functions of these critical virulence determinants. Several aspects
      of Helicobacter pylori physiology were newly explored this year and evaluated for
      their functions during stomach colonization, including a fascinating role for the
      essential protease HtrA in allowing access of H. pylori to the basolateral side
      of the gastric epithelium through cleavage of the tight junction protein E
      cadherin to facilitate CagA delivery. Molecular biology tools standard in model
      bacteria, including regulated gene expression during animal infection and
      fluorescent reporter gene fusions, were newly applied to H. pylori to explore
      functions for urease beyond initial colonization and establish high salt
      consumption as a mediator of gene expression changes. New sequencing technologies
      enabled validation of long postulated roles for DNA methylation in regulating H.
      pylori gene expression. On the cell biology side, elegant work using lineage
      tracing in the murine model and organoid primary cell culture systems has
      provided new insights into how H. pylori manipulates gastric tissue functions,
      locally and at a distance, to promote its survival in the stomach and induce
      pathologic changes. Finally, new work has bolstered the case for genomic
      variation as an important mechanism to generate phenotypic diversity during
      changing environmental conditions in the context of diet manipulation in animal
      infection models and during human experimental infection after vaccination.

PMID- 30203583
TI  - Helicobacter pylori and nonmalignant upper gastrointestinal diseases.
AB  - The review of the most important recent publications concerning the relation of
      Helicobacter pylori with peptic ulcer disease (PUD), noninvestigated and
      functional dyspepsia, and gastroesophageal reflux disease (GERD) is presented. H.
      pylori remains the main etiopathogenetic factor in complicated and uncomplicated
      PUD. Nevertheless, the role of nonsteroidal anti-inflammatory drugs (NSAIDs) and
      aspirin is increasing. The novel data did not confirm that PUD caused by NSAIDs
      and aspirin is less symptomatic. The role of glucocorticoids, immunosuppressants,
      and antidepressants seems to be of some importance. Although the involvement of
      H. pylori in functional dyspepsia is controversial, several data support the
      importance of H. pylori-induced gastritis in the pathogenesis of dyspeptic
      symptoms. Recent interventional studies have reported that H. pylori eradication
      improves dyspepsia mainly in areas with a high prevalence of this bacterium.
      Novel data regarding the relation of gastrointestinal peptides, ghrelin and
      obestatin, with H. pylori infection are also presented. Intriguing findings
      support the involvement of the gastric microbiota in the causation of chronic
      functional dyspepsia. Finally, some data concerning negative, positive, or
      neutral associations of H. pylori with gastroesophageal reflux disease (GERD)
      were published. In this context, today there is no evidence indicating that H.
      pylori eradication could worsen the symptoms or the course of GERD.

PMID- 30203584
TI  - Diagnosis of Helicobacter pylori infection.
AB  - The progress this year in Helicobacter pylori diagnosis concerned essentially
      endoscopy and molecular techniques. New endoscopy techniques such as blue laser
      imaging and magnifying narrow band imaging allow the visualization of mucosal
      aspects representing H. pylori infection, intestinal metaplasia, and even
      ambiguous early gastric cancer. Several real-time PCRs have also been used either
      to quantify H. pylori or to detect mutations associated with clarithromycin
      resistance in gastric biopsies or applied on gastric juice, stool specimens, or
      the oral cavity. The presence of H. pylori in free-living amebae purified from
      wastewater and drinking water was also determined by PCR and sequencing, as well
      as culture from a few wastewater samples. Among the noninvasive methods, the urea
      breath test was used in different conditions, including with a new test meal,
      which is claimed to avoid the proton-pump inhibitor washout period before
      testing. Several articles concerning antibody detection and stool antigen test
      were also published.

PMID- 30203585
TI  - Treatment of Helicobacter pylori infection in 2018.
AB  - Treatment options for the eradication of Helicobacter pylori continue to evolve.
      There have been many guidelines for H. pylori treatment published, which may lead
      to some confusion. However, most are in agreement with the most recent iteration
      of the Maastricht treatment guidelines. Triple therapy is still the most
      frequently used treatment, especially in areas of low clarithromycin resistance.
      Its best results are achieved when taken for a minimum of 10 days and with high
      dose acid suppression. Quadruple therapy is gaining in popularity particularly in
      areas with increasing resistance to standard triple therapy. Whether three
      antibiotics, or bismuth and two antibiotics are used, excellent eradication rates
      are achieved, albeit with increased side effects. Levofloxacin second-line
      therapy is widely used; however bismuth, when available, is an increasingly
      successful option. Sequential therapy is challenging in terms of compliance and
      is no longer recommended. This past year witnessed a notable increase in the
      number of studies based on antimicrobial susceptibility testing and tailored
      eradication therapy, reflecting the role of culture-guided treatment, which may
      well represent the future of H. pylori treatment and prevent the inappropriate
      use of antibiotics.

PMID- 30203586
TI  - Other Helicobacters and the gastric microbiome.
AB  - The current article is a review of the most important, accessible, and relevant
      literature published between April 2017 and March 2018 on other Helicobacters and
      the gastric microbiome. The first part of the review focuses on literature
      describing non-Helicobacter pylori-Helicobacter (NHPH) infections in humans and
      animals whilst the subsequent section focuses specifically on the human gastric
      microbiome. Novel diagnostic methods as well as new NHPHs species have been
      identified in recent studies. Furthermore, our knowledge about the pathogenesis
      of NHPH infections has been further enhanced by important fundamental studies in
      cell lines and animal models. Over the last year, additional insights over the
      prevalence and potential prevention strategies of NHPHs have also been reported.
      With regard to understanding the gastric microbiome, new information detailing
      the structure of the gastric microbiota at different stages of H. pylori
      infection, within different patient geographical locations, was documented. There
      was also a study detailing the impact of proton-pump inhibitor usage and the
      effect on the gastric microbiome. Newer analysis approaches including defining
      the active microbiome through analysis of RNA rather than DNA-based sequencing
      were also published allowing the first assessments of the functional capabilities
      of the gastric microbiome.

PMID- 30203587
TI  - Epidemiology of Helicobacter pylori infection.
AB  - This review provides the most recent data concerning the epidemiology of
      Helicobacter pylori infection. Overall, the trend of declining prevalence of H.
      pylori infection is continuing, with major evidence available from studies in
      Europe. However, in some parts of the world, for example, in some countries in
      the Middle East, the prevalence has remained relatively stable. A number of
      systematic reviews and meta-analyses have been published during the past year
      indicating the lowest prevalence rates of the infection in Oceania (24.4%), the
      highest in Africa (79.1%), and the global annual recurrence rate of H. pylori
      (4.3%). The recurrence rates were found to be directly related to the human
      development index and prevalence of infection. Several studies have addressed the
      correlation between H. pylori infection and sociodemographic conditions, source
      of drinking water and dietary factors. A hypothesis on the role of insects and
      yeasts in transmitting H. pylori has been suggested and addressed. Helicobacter
      sp. have been found in flow flies in Brazil. So far there is no evidence
      available that H. pylori may survive and persist on the outer body of the fly.

PMID- 30203588
TI  - XXX1st International Workshop on Helicobacter & Microbiota in Inflammation &
      Cancer, 14-15 September 2018, Kaunas, Lithuania.

PMID- 30203589
TI  - Gastric cancer: epidemiology, prevention, and therapy.
AB  - Gastric cancer (GC) is still the third leading cause of cancer death in both
      sexes worldwide. Helicobacter pylori infection is the most important risk factor
      for GC and, in spite of the consistent trend of a decreasing incidence, in 2015
      approximately 4.4 billion individuals-more than half the world's population-were
      infected with H. pylori. The birth cohort pattern of decreased H. pylori
      infection reported in a systematic review contributes to explain the declining GC
      mortality in Japan. Current trends in estimated annual percentage change of GC
      incidence foreshadow expected reversals in both falling incidence and male
      predominance among US non-Hispanic whites. Combining serum pepsinogen 1 and H.
      pylori serology was shown to be useful for GC risk stratification in a Finnish
      population. Gastritis staging by operative link on gastritis assessment was
      confirmed to be reliable in predicting GC risk in a large prospective study. In a
      randomized trial from South Korea, H. pylori eradication therapy significantly
      reduced the rates of metachronous GC in patients who received curative endoscopic
      resection for early GC. A study based on a territory-wide health care database of
      the Hong Kong Hospital Authority showed that aspirin use is associated with a
      reduced GC risk. Another study based on the same database showed that proton pump
      inhibitors increase GC risk, but methodological biases have most likely acted as
      confounders. Confirmatory data on the role of endoscopic submucosal dissection in
      patients with early GC have been published. The phase III FLOT4 trial has shown
      that the FLOT triplet regimen (docetaxel, oxaliplatin, leucovorin, and 5
      fluorouracil) improves the outcome of patients with GC and locoregional disease
      as compared to the ECF triplet (epirubicin, cisplatin, and 5-fluorouracil). In
      the phase III ATTRACTION-2 trial, nivolumab was shown to be an effective
      treatment option with a relative safe profile for heavily pretreated patients
      with advanced GC.

PMID- 30203590
TI  - Helicobacter pylori and extragastric diseases.
AB  - Many studies have been performed in the last year concerning the potential role
      of Helicobacter pylori in different extragastric diseases, reinforcing the idea
      that specific microorganisms may cause diseases even far from the primary site of
      infection. While the role of H. pylori on idiopathic thrombocytopenic purpura,
      sideropenic anemia, and vitamin B12 deficiency has been well established, there
      is a growing interest in other conditions, such as cardiovascular, neurologic,
      dermatologic, obstetric, immunologic, and metabolic diseases. Concerning
      neurologic diseases, there is a great interest in cognitive impairment and
      neurodegeneration. The aim of this review was to summarize the results of the
      most relevant studies published over the last year on this fascinating topic.

PMID- 30203591
TI  - Helicobacter pylori and some aspects of gut microbiota in children.
AB  - Helicobacter pylori infection in children differs from infection in adults in
      many aspects. The rate of infection, epidemiology, clinical presentations and
      complications, the applicability of diagnostic tests, antibiotic resistance,
      treatment options, and success rates differ significantly. Due to all these
      differences, management guidelines for children and adults differ also
      substantially. In 2017, the Updated ESPGHAN and NASPGHAN Guidelines on the
      management of H. pylori infection in children were published, emphasizing the
      differences in clinical presentation and indications for treatment, stating that
      the primary goal of clinical investigation in children is to identify the cause
      of upper gastrointestinal symptoms rather than the presence of H. pylori
      infection. Therefore, the diagnosis should be based on upper endoscopy, and the
      "test and treat strategy" should not be used in children. Due to an increasing
      rate of antibiotic resistance worldwide, the updated guidelines recommend broader
      use of antimicrobial susceptibility testing for H. pylori strains in order to
      tailor eradication treatment accordingly. Moreover, treatment in children should
      be prescribed only when indicated and should be based on the rate of eradication
      in local populations aiming for treatment success above 90%. During the last two
      decades there has been a steady decrease in the rate of H. pylori infection in
      both children and adults in the Western world. Two recent publications studying
      the incidence of H. pylori infection confirmed that early childhood is a time for
      acquisition of infection both in industrialized and nonindustrialized countries.
      In addition, they showed that H. pylori could be acquired outside the family. In
      respect to the inverse association between H. pylori and allergy, a longitudinal
      study demonstrated that early exposure to H. pylori at any age was inversely
      associated with atopy and allergic conditions.

PMID- 30203592
TI  - Designing cancer immunotherapy trials with random treatment time-lag effect.
AB  - In some clinical settings such as the cancer immunotherapy trials, a treatment
      time-lag effect may be present and the lag duration possibly vary from subject to
      subject. An efficient study design and analysis procedure should not only take
      into account the time-lag effect but also consider the individual heterogeneity
      in the lag duration. In this paper, we present a Generalized Piecewise Weighted
      Logrank (GPW-Logrank) test, designed to account for the random time-lag effect
      while maximizing the study power with respect to the weights. Based on the
      proposed test, both analytic and numeric approaches are developed for the sample
      size and power calculation. Asymptotic properties are derived and finite sample
      efficiency is evaluated in simulations. Compared with the standard practice
      ignoring the delayed effect, the proposed design and analysis procedures are
      substantially more efficient when a random lag is expected; further, compared
      with the existing methods by Xu et al considering the fixed time-lag effect, the
      proposed approaches are significantly more robust when the lag model is
      misspecified. An R package (DelayedEffect.Design) is developed for
      implementation.

PMID- 30203593
TI  - Ultrasound Findings in Patients With Femoracetabular Impingement Without
      Radiographic Osteoarthritis: A Pilot Study.
AB  - OBJECTIVES: To assess ultrasound (US) abnormalities in patients with clinical and
      radiographic features of femoracetabular impingement (FAI) without radiologic
      osteoarthritis. METHODS: This study included patients aged 50 years or younger
      with hip pain and clinical and radiographic signs suggestive of FAI but without
      radiographic hip osteoarthritis. Demographic characteristics, the symptom
      duration, and the radiologic type of FAI were recorded. Ultrasound examinations
      assessed for anterior labral abnormalities, osteophytes, bone cortex
      irregularities, capsular distension, and acetabulofemoral and femoral head-to
      neck distances. A balanced group of healthy volunteers was used as control
      participants. RESULTS: Forty-four patients with FAI were evaluated. Ultrasound
      changes were found in 93.2% of patients, with 63.6% showing some kind of labral
      abnormality, 40.9% showing articular cartilage abnormalities, 38.6% showing bone
      contour irregularities, and 29.5% showing osteophytes. The cartilage width and
      symptom duration were inferior in patients with a damaged articular surface
      compared with those without (P = .005 and .012, respectively). Patients showing
      osteophytes on US examinations were slightly older (P = .048). Patients with cam
      type FAI were more frequently male (P = .0001) and younger (P = .022) compared
      with those who had pincer-type FAI and also had a shorter symptom duration (P <
      .05). Patients with symptoms for 2 years or less had a shorter femoral cartilage
      width (P = .027). Femoral head-to-neck distances were shorter in patients
      compared with controls (P = .0005). Only 1 patient in the control group showed
      some US abnormality. CONCLUSIONS: Ultrasound showed detected abnormalities in a
      significant proportion of patients with symptomatic FAI in early phases of the
      disease. Additional longitudinal studies are warranted to establish the
      prognostic importance of these US changes.(c) 2018 by the American Institute of
      Ultrasound in Medicine.

PMID- 30203594
TI  - Role of Plasma Exchange in the Management of Pediatric Optic Neuritis With
      Antibodies Against Myelin Oligodendrocyte Glycoprotein.

PMID- 30203595
TI  - Association of dyslipidaemia and oral statin use, and dry eye disease symptoms in
      the Blue Mountains Eye Study.
AB  - IMPORTANCE: There is limited literature on oral statin use and its association
      with dry eye. BACKGROUND: To analyse the association between dyslipidaemia, use
      of oral statin drugs, and symptoms of dry eye disease (DED) among older adults.
      DESIGN: Population-based study. PARTICIPANTS: Participants of the Blue Mountains
      Eye Study III (BMESIII), a large cohort study in suburban Sydney, aged 60 years
      or older (mean age = 74, range = 60-97, n = 1680) were analysed. METHODS:
      Information on DED symptoms and statin use were obtained from an interviewer
      administered questionnaire. Serum lipid profiles were determined from fasting
      blood tests. MAIN OUTCOME MEASURES: The association of various DED symptoms, as
      well as their number and their severity, with dyslipidaemia and oral statin
      intake was evaluated. RESULTS: At least one DED symptom was reported in 52% (n =
      1029) of the population. Patients with hypercholesterolaemia (>5.5 mmol/L) did
      not report more DED symptoms than those without hypercholesterolaemia. Neither
      serum high-density lipoprotein nor low-density lipoprotein levels were associated
      with any DED symptoms. Patients taking oral statins were more likely to report
      one or more moderate to severe symptoms of DED (odds ratio: 2.054, 95% confidence
      interval: 1.281-3.295). CONCLUSIONS AND RELEVANCE: The association between oral
      statin use and presence of moderate to severe DED symptomatology is a novel
      finding that deserves further mechanistic and clinical correlation in order to
      determine its potential, or lack thereof, for the management of dry eye.

PMID- 30203596
TI  - Study of the mechanisms of crocetin-induced differentiation and apoptosis in
      human acute promyelocytic leukemia cells.
AB  - Crocetin, the major carotenoid in saffron, exhibits potent anticancer effects.
      However, the antileukemic effects of crocetin are still unclear, especially in
      primary acute promyelocytic leukemia (APL) cells. In the current study, the
      potential antipromyelocytic leukemia activity of crocetin and the underlying
      molecular mechanisms were investigated. Crocetin (100 uM), like standard anti-APL
      drugs, all-trans retinoic acid (ATRA, 10 uM) and As2 O 3 (arsenic trioxide, 50
      uM), significantly inhibited proliferation and induced apoptosis in primary APL
      cells, as well as NB4 and HL60 cells. The effect was associated with the
      decreased expressions of prosurvival genes Akt and BCL2, the multidrug resistance
      (MDR) proteins, ABCB1 and ABCC1 and the inhibition of tyrosyl-DNA
      phosphodiesterase 1 (TDP1), while the expressions of proapoptotic genes CASP3,
      CASP9, and BAX/BCL2 ratio were significantly increased. In contrast, crocetin at
      relatively low concentration (10 uM), like ATRA (1 uM) and As 2 O 3 (0.5 uM),
      induced differentiation of leukemic cells toward granulocytic pattern, and
      increased the number of differentiated cells expressing CD11b and CD14, while the
      number of the immature cells expressing CD34 or CD33 was decreased. Furthermore,
      crocetin suppressed the expression of clinical marker promyelocytic
      leukemia/retinoic acid receptor-alpha ( PML/RARalpha) in NB4 and primary APL
      cells, and reduced the expression of histone deacetylase 1 ( HDAC1) in all
      leukemic cells. The results suggested that crocetin can be considered as a
      candidate for future preclinical and clinical trials of complementary APL
      treatment.

PMID- 30203597
TI  - Perlecan/HSPG2: Signaling role of domain IV in chondrocyte clustering with
      implications for Schwartz-Jampel Syndrome.
AB  - Perlecan/heparan sulfate proteoglycan 2 (HSPG2), a large HSPG, is indispensable
      for the development of musculoskeletal tissues, where it is deposited within the
      pericellular matrix (PCM) surrounding chondrocytes and disappears nearly
      completely at the chondro-osseous junction (COJ) of developing long bones.
      Destruction of perlecan at the COJ converts an avascular cartilage compartment
      into one that permits blood vessel infiltration and osteogenesis. Mutations in
      perlecan are associated with chondrodysplasia with widespread musculoskeletal and
      joint defects. This study elucidated novel signaling roles of perlecan core
      protein in endochondral bone formation and chondrocyte behavior. Perlecan
      subdomains were tested for chondrogenic properties in ATDC5 cells, a model for
      early chondrogenesis. A region within domain IV of perlecan (HSPG2 IV-3) was
      found to promote rapid prechondrocyte clustering. Introduction of the mutation
      (R3452Q) associated with the human skeletal disorder Schwartz-Jampel syndrome
      limited HSPG2 IV-3-induced clustering. HSPG2 IV-3 activity was enhanced when
      thermally unfolded, likely because of increased exposure of the active motif(s).
      HSPG2 IV-3-induced clustering was accompanied by the deactivation of key
      components of the focal adhesion complex, FAK and Src, with increased messenger
      RNA (mRNA) levels of precartilage condensation markers Sox9 and N-cadherin (
      Cdh2), and cartilage PCM components collagen II ( Col2a1) and aggrecan ( Acan).
      HSPG2 IV-3 reduced signaling through the ERK pathway, where loss of ERK1/2
      phosphorylation coincided with reduced FoxM1 protein levels and increased mRNA
      levels cyclin-dependent kinase inhibitor 1C (Cdkn1c) and activating transcription
      factor 3 ( Atf3), reducing cell proliferation. These findings point to a critical
      role for perlecan domain IV in cartilage development through triggering
      chondrocyte condensation.

PMID- 30203598
TI  - In Vivo Anticancer Activity of a Nontoxic Inert Phenolato Titanium Complex: High
      Efficacy on Solid Tumors Alone and Combined with Platinum Drugs.
AB  - Due to the toxicity of platinum compounds used in the clinic as anticancer
      chemotherapies, titanium serves as a safe and attractive alternative. Lately, we
      introduced a new family of Ti complexes based on readily available phenolato
      ligands, demonstrating incredibly high hydrolytic stability, with the lead
      compound phenolaTi demonstrating wide cytotoxic activity toward the NCI-60 panel
      of human cancer cell lines, with an average GI50 value of 4.7+/-2 MUm. Herein, we
      evaluated in vivo: a) the safety, and b) the growth inhibitory capacity
      (efficacy) of this compound. PhenolaTi was found to be effective in vivo against
      colon (CT-26) and lung (LLC-1) murine cell lines in syngeneic hosts and toward a
      human colon cancer (HT-29) cell line in immune-deficient (Nude) mice, with an
      efficacy similar to that of known chemotherapy. Notably, no clinical signs of
      toxicity were observed in the treated mice, namely, no effect on body weight,
      spleen weight or kidney function, unlike the effects observed with the positive
      control Pt drugs. Studies of combinations of phenolaTi and Pt drugs provided
      evidence that similar efficacy with decreased toxicity may be achieved, which is
      highly valuable for medicinal applications.

PMID- 30203599
TI  - Which is the most important factor in the relationship between cardiovascular
      events and obstructive sleep apnea: Blood pressure level, blood pressure
      variability or baroreflex sensitivity?

PMID- 30203601
TI  - Reducing the Clinical Medicine and Population Health Divide.

PMID- 30203600
TI  - Diversity in Medical Device Clinical Trials: Do We Know What Works for Which
      Patients?
AB  - : Policy Points: A 1993 law required the National Institutes of Health to include
      women and racial and ethnic minorities in relevant research studies. Most federal
      health agencies adopted the same policy, but the US Food and Drug Administration
      (FDA) did not. A 2012 law encouraged the FDA to ensure that new medical products
      be analyzed for safety and effectiveness for key demographic patient groups. Our
      study of high-risk medical devices reviewed by the FDA in 2014-2017 found that
      due to lack of patient diversity and publicly available data, clinicians and
      patients often cannot determine which devices are safe and effective for specific
      demographic groups. CONTEXT: Demographic differences can influence the safety and
      effectiveness of medical devices; however, clinical trials of devices for adults
      have historically underrepresented women, people of color, and patients over age
      65. The US Food and Drug Administration (FDA) Safety and Innovation Act became
      law in 2012, encouraging greater diversity and subgroup analyses. In 2013, the
      FDA reported that there was diversity in clinical trials considered "pivotal" for
      approval decisions and that subgroup analyses were conducted for most
      applications for the highest-risk medical devices. However, the FDA's report did
      not specify whether analyses included sufficient numbers to be meaningful,
      whether analyses were conducted for most major subgroups, or whether analyses
      included safety, effectiveness, or accuracy. METHODS: We examined publicly
      available documents for all 22 medical devices that the FDA designated "highest
      risk" or "novel," were reviewed through the premarket approval pathway, and were
      scrutinized at FDA public meetings from 2014 to 2017. We evaluated patient
      demographics and subgroup analyses for all pivotal trials. FINDINGS: Only 3 (14%)
      of the devices provided subgroup analyses for both effectiveness and safety or
      both sensitivity and selectivity for gender, race, and age. However, 55% of the
      devices reported both of those subgroup analyses for at least 1 of the 3
      subgroups. Whether analyses were reported or not, the number of patients in most
      subgroups was too small to draw meaningful conclusions. Subgroup analyses were
      more likely to be reported to the FDA's Advisory Committees than in the FDA's
      public reviews or labeling. CONCLUSIONS: Despite a law encouraging more diversity
      and subgroup analyses in pivotal trials used as the basis for FDA approval, the
      results of our study indicate relatively few subgroup analyses are publicly
      available for the highest-risk and novel medical devices. The lack of subgroup
      analyses makes it impossible to inform patients or physicians as to whether many
      newly approved medical devices are safe and effective for specific demographic
      subgroups defined by gender, race, and age.

PMID- 30203602
TI  - Surprising Statistics on the Uninsured.

PMID- 30203604
TI  - Climate Denial and a (Hopeful) Lesson From History.

PMID- 30203603
TI  - Impact of Pharmacists on Access to Vaccine Providers: A Geospatial Analysis.
AB  - : Policy Points: Policymakers in the United States should consider expanding
      pharmacy practice laws to allow pharmacists to vaccinate adolescents as a way to
      improve geographic access to adolescent vaccines, particularly for human
      papillomavirus (HPV) vaccine, which has low uptake. Our state-level analysis
      showed that pharmacists are more geographically dispersed than primary care
      physicians in the US state of Texas. Including pharmacists among available
      adolescent vaccine providers would improve the geographic distribution of vaccine
      providers, especially in areas with an inadequate number of primary care
      physicians. CONTEXT: The largest disparities in human papillomavirus (HPV)
      vaccination in the United States are due to geography. One potential way of
      addressing these disparities is by improving geographic access to HPV
      vaccination. Two federal panels have recommended including community pharmacists
      as HPV vaccine providers as a strategy to improve opportunities for HPV
      vaccination for adolescents. We sought to evaluate whether community pharmacists
      can improve the number of vaccine providers in areas with primary care physician
      shortages in the US state of Texas. METHODS: We gathered publicly available
      physician and pharmacist 2016 workforce data from the Texas Medical Board and
      Board of Pharmacy. We conducted geospatial analysis of census tracts to analyze
      the distribution of physicians and pharmacists and how pharmacists change vaccine
      provider coverage across the state. FINDINGS: Census tracts with high numbers of
      physicians per capita tended to be located near one another, in 5 of 5 analyses
      of Moran's I (median = .04). In contrast, pharmacist rates were not spatially
      dependent on census tract in any of our analyses. If pharmacists were added to
      primary care physicians as vaccine providers, 35% of urban census tracts that
      previously had inadequate coverage would be adequately covered, while 18% of
      inadequately covered rural census tracts would become adequately covered.
      Overall, when pharmacists were included with primary care physicians as vaccine
      providers, vaccine providers per capita increased in 2,413 of the 4,508 urban
      census tracts (54%), while the rate increased in 223 of 746 rural census tracts
      (30%). CONCLUSIONS: Pharmacists are more geographically dispersed across census
      tracts than primary care physicians. As a result, adding pharmacists to the
      workforce would increase the availability of vaccine providers in areas with
      inadequate primary care provider coverage.

PMID- 30203607
TI  - Characterization of the vaginal microbiome during cytolytic vaginosis using high
      throughput sequencing.
AB  - BACKGROUND: Cytolytic vaginosis (CV) is a common disease that results in
      pruritus, dyspareunia, and vulvar dysuria. However, the pathological mechanisms
      of the disease are still unclear. Compared to traditional methods, high
      throughput sequencing can obtain more accurate qualitative and quantitative
      information on the microbiome. METHODS: We collected 75 samples from 32 healthy
      women (average age 44 +/- 8) and 43 patients with CV (average age 38 +/- 8). We
      used high-throughput sequencing of the 16S rRNA V3-V4 region to characterize and
      compare the vaginal microbiota of patients with CV and healthy women and to
      identify potential biomarkers for CV. RESULTS: The vaginal pH of patients with CV
      was <=3.8, and the vaginal concentration of H2 O2 was >=2 MUmol/L. Colony
      densities of Lactobacillus spp. in patients with CV ranged from +++ (5-30) to
      ++++ (>30) and were significantly higher than those in healthy women. High
      throughput sequencing showed that Lactobacillus was the most prominent genus both
      in patients with CV and in healthy women, with abundances of 83.8% and 97.2%,
      respectively (P < 0.001). Lactobacillus crispatus was more abundant in patients
      with CV, whereas Lactobacillus sp. L-YJ was more abundant in healthy women, with
      area under the curve (AUC) values of 0.9375 and 0.8379, respectively. CONCLUSION:
      The abundance of Lactobacillus spp. in CV patients was significantly different
      from that of healthy patients. Two suitable biomarkers, L. crispatus and
      Lactobacillus sp. L-YJ, were identified. These results will be useful for the
      identification of women at risk of serious illness before they develop obvious
      symptoms.

PMID- 30203606
TI  - Patient-Centered Insights: Using Health Care Complaints to Reveal Hot Spots and
      Blind Spots in Quality and Safety.
AB  - : Policy Points: Health care complaints contain valuable data on quality and
      safety; however, there is no reliable method of analysis to unlock their
      potential. We demonstrate a method to analyze health care complaints that
      provides reliable insights on hot spots (where harm and near misses occur) and
      blind spots (before admissions, after discharge, systemic and low-level problems,
      and errors of omission). Systematic analysis of health care complaints can
      improve quality and safety by providing patient-centered insights that localize
      issues and shed light on difficult-to-monitor problems. CONTEXT: The use of
      health care complaints to improve quality and safety has been limited by a lack
      of reliable analysis tools and uncertainty about the insights that can be
      obtained. The Healthcare Complaints Analysis Tool, which we developed, was used
      to analyze a benchmark national data set, conceptualize a systematic analysis,
      and identify the added value of complaint data. METHODS: We analyzed 1,110 health
      care complaints from across England. "Hot spots" were identified by mapping
      reported harm and near misses onto stages of care and underlying problems. "Blind
      spots" concerning difficult-to-monitor aspects of care were analyzed by examining
      access and discharge problems, systemic problems, and errors of omission.
      FINDINGS: The tool showed moderate to excellent reliability. There were 1.87
      problems per complaint (32% clinical, 32% relationships, and 34% management).
      Twenty-three percent of problems entailed major or catastrophic harm, with
      significant regional variation (17%-31%). Hot spots of serious harm were safety
      problems during examination, quality problems on the ward, and institutional
      problems during admission and discharge. Near misses occurred at all stages of
      care, with patients and family members often being involved in error detection
      and recovery. Complaints shed light on 3 blind spots: (1) problems arising when
      entering and exiting the health care system; (2) systemic failures pertaining to
      multiple distributed and often low-level problems; and (3) errors of omission,
      especially failure to acknowledge and listen to patients raising concerns.
      CONCLUSIONS: The analysis of health care complaints reveals valuable and uniquely
      patient-centered insights on quality and safety. Hot spots of harm and near
      misses provide an alternative data source on adverse events and critical
      incidents. Analysis of entry-exit, systemic, and omission problems provides
      insight on blind spots that may otherwise be difficult to monitor. Benchmark data
      and analysis scripts are downloadable as supplementary files.

PMID- 30203609
TI  - Choroidal blood flow after the first intravitreal ranibizumab injection in
      neovascular age-related macular degeneration patients.
AB  - PURPOSE: To analyse choroidal blood flow (ChBF) changes after the first
      intravitreal ranibizumab injection in naive, age-related macular degeneration
      (ARMD) patients. METHODS: Subfoveal ChBF was assessed by laser Doppler flowmetry
      (LDF) in newly diagnosed ARMD patients. Both treated and untreated eyes were
      assessed in each subject at each visit before the first intravitreal ranibizumab
      injection as well as 24 hr (day 1) and 7 days after (day 7). Central macular
      thickness (CMT), best-corrected visual acuity (BVCA), systemic haemodynamic
      parameters and LDF parameters were evaluated at each visit. Nonparametric tests
      were used to compare data between visits and between treated and untreated eyes.
      RESULTS: Seventeen ARMD patients were included (12 women and five men, 78 +/- 8
      years old). At day 7 postintravitreal ranibizumab injection, the normalized
      choroidal blood velocity (ChBVel) change in the treated eye group was significant
      (-10.2%; p = 0.006). The choroidal blood volume (ChBVol) did not change
      significantly after intravitreal injection of ranibizumab. There was a trend for
      a reduction in ChBF at day 7 (-9.1%, p = 0.08). The sensitivity of the experiment
      was 12% for ChBVel, 16% for ChBVol and 9% for ChBF. CONCLUSION: In conclusion,
      the laser Doppler technique provides feasible and noninvasive measurements of
      blood flow parameters before and after intravitreal injection of antivascular
      endothelial growth factor (anti-VEGF) in patients with exudative ARMD. Choroidal
      blood velocity decreased as early as 7 days after intravitreal ranibizumab
      injection, suggesting a vasoconstriction effect of anti-VEGF in large choroidal
      vessels in front of choriocapillaris (the site of LDF measurement).

PMID- 30203608
TI  - Outcomes after transcatheter aortic valve replacement in patients with low versus
      high gradient severe aortic stenosis in the setting of preserved left ventricular
      ejection fraction.
AB  - BACKGROUND: Transcatheter aortic valve replacement (TAVR) for low gradient (LG)
      severe aortic stenosis (AS) with preserved left ventricular ejection fraction
      (LVEF) remains an area of clinical uncertainty. METHODS: Retrospective review
      identified 422 patients who underwent TAVR between September 4, 2014 and July 1,
      2016. Procedural indication other than severe AS (n = 22) or LVEF <50% (n = 98)
      were excluded. Outcomes were defined by valve academic research consortium two
      criteria when applicable and compared between LG (peak velocity <4.0 m/s and mean
      gradient <40 mmHg; n = 73) and high gradient (HG) (n = 229) groups. The LG group
      was further categorized as low stroke volume index (SVI) (n = 41) or normal SVI
      (n = 32). Median follow-up was 747 days [interquartile range 220-1013]. RESULTS:
      Baseline thirty-day mortality risk (LG 6.2% [3.8-8.1] vs HG 5.7% [4.1-7.4], P =
      0.43) did not differ between groups. Short-term outcomes, including procedural
      success rate (86.1% vs 88.8%, P = 0.53), peri-procedural complications (intra
      procedural heart block: 6.8% vs 7.9%, P = 0.99; permanent pacemaker placement:
      11.0% vs 13.6%, P = 0.69; moderate paravalvular regurgitation: 2.7% vs 1.3%, P =
      0.60), and all-cause in-hospital mortality (2.7% vs 0.9%, P = 0.25) did not
      differ between LG and HG groups. On long-term follow-up, all-cause mortality also
      did not differ between LG and HG groups (6.8% vs 10.0%, plog-rank  = 0.33) or
      between the LG low SVI (9.8%), LG normal SVI (3.1%), and HG (10.0%) groups (plog
      rank  = 0.39). CONCLUSION: Patients with preserved LVEF undergoing TAVR for
      severe AS with LG, including LG with low SVI, have no significant difference in
      adverse outcomes when compared to patients with HG.

PMID- 30203610
TI  - The opioid and pain intensity index-A proposal.

PMID- 30203611
TI  - Response to: The Opioid and Pain intensity Index - a proposal.

PMID- 30203612
TI  - Absence of the common bile duct.

PMID- 30203613
TI  - Endovascular embolization of a giant hepatic artery aneurysm.

PMID- 30203614
TI  - Locally recurrent lentigo maligna within a skin graft: a case report.

PMID- 30203615
TI  - LncRNA DSCAM-AS1 acts as a sponge of miR-137 to enhance Tamoxifen resistance in
      breast cancer.
AB  - OBJECTIVE: To investigate the influence of long noncoding RNA (lncRNA) DSCAM-AS1
      on the propagation and apoptosis of Tamoxifen-resistant (TR) breast cancer cells
      via regulation of mircoRNA (miR)-137 and epidermal growth factor receptor pathway
      substrate 8 (EPS8). METHODS: Data of GSE5840 downloaded from the Gene Expression
      Omnibus database were utilized to screen out aberrantly expressed lncRNA and
      messenger RNA in breast cancer tissue samples. The expressions of DSCAM-AS1, miR
      137, and EPS8 were determined by quantitative real time polymerase chain reaction
      (qRT-PCR). Cell lines were screened by half maximal inhibitory concentration (IC
      50 ). 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT)
      assay and the flow cytometry assay were used to detect cell proliferation,
      apoptosis, and cell cycle. The relationship among DSCAM-AS1, miR-137, and EPS8
      was studied by miRcode, TargetScan, and Pearson correlation coefficient. A
      xenograft mouse model experiment was performed to demonstrate the effect of DSCAM
      AS1 and EPS8 on tumor growth in vivo. RESULTS: LncRNA DSCAM-AS1 and EPS8 were
      significantly upregulated, whereas miR-137 was downregulated in TR tissues. DSCAM
      AS1 could promote the Tamoxifen resistance of breast cancer, and it was
      negatively correlated with miR-137, whereas positively correlated with the
      expression of EPS8 in TR breast cancer tissues. Furthermore, miR-137 could
      inhibit tumor development and arrest cell cycle at the G0/G1 phase by targeting
      the 3'-UTR of EPS8. DSCAM-AS1 targeted miR-137 and EPS8 to promote propagation of
      TR breast cancer cells and inhibit cell apoptosis. CONCLUSION: LncRNA DSCAM-AS1
      acts as a competing endogenous RNA of miR-137 and regulates EPS8 to promote cell
      reproduction and suppresses cell apoptosis in TR breast cancer.

PMID- 30203616
TI  - The expanding spectrum of antibody-mediated rejection: Should we include cases
      where no anti-HLA donor-specific antibody is detected?

PMID- 30203617
TI  - A new mite IPM strategy: predator avoidance behaviour resulting from the
      synergetic effects of predator release and acaricide-treated nets.
AB  - BACKGROUND: Tetranychus evansi and T. urticae spider mites are known major pests
      of Solanaceae. Smallholders in Africa rely heavily on pesticide treatments.
      However, farmers claim that pesticides are generally ineffective despite high
      frequency sprays. New management solutions are thus urgently needed. This study
      assessed the efficacy of using acaricide-treated nets combined with predatory
      mite release for controlling spider mites. RESULTS: The results showed the
      acaricide-treated net alone was more effective at reducing numbers of T. urticae
      than T. evansi. We observed the opposite for release of the predatory mite
      Phytoseiulus longipes. This difference could be explained by the specific
      dispersion strategies of the two spider mite pests; T. evansi is gregarious,
      whereas T. urticae dispersed rapidly. Joint application of both techniques
      resulted in a synergetic effect that reduced T. evansi and T. urticae spider mite
      numbers close to zero. The synergetic effect could be explained by predator
      avoidance behaviour of the prey spider mites, resulting in higher prey trapping
      and killing rates on acaricide-treated nets, while P. longipes fed on spider mite
      eggs. CONCLUSION: These techniques are profitable for smallholders as they are
      not expensive and avoid residues on the crop. (c) 2018 Society of Chemical
      Industry.

PMID- 30203618
TI  - Benefits of kidney transplantation for a national cohort of patients aged 70
      years and older starting renal replacement therapy.
AB  - Our objectives were to evaluate kidney transplantation survival benefit in people
      aged >=70 who were receiving renal replacement therapy (RRT) and to identify
      their risk factors for posttransplant mortality. This study included all patients
      in the national French Renal Epidemiology and Information Network registry who
      started RRT between 2002 and 2013 at age >=70. Mortality risk was compared
      between patients with transplants; on the waiting list; and on dialysis matched
      for age, gender, comorbidities, and time on dialysis. Of the 41 716 elderly
      patients starting RRT, 1219 (2.9%) were on the waiting list and 877 (2.1%)
      underwent transplantation during the follow-up. Until month 3, transplant
      patients had a risk of death triple that of the wait-listed group. Although the
      risk was halved at month 9, the perioperative risk was still not offset by month
      36. Compared with matched dialysis patients (n = 2183), transplant patients were
      not at significantly increased perioperative risk and had a lower mortality risk
      starting at month 3. Risk factors for posttransplant mortality were diabetes,
      cardiovascular comorbidities, and dialysis duration >2 years. Among older
      dialysis patients, 20% had neither cardiovascular comorbidity nor diabetes.
      Systematic early assessment of the eligibility of elderly patients for kidney
      transplantation is recommended to expand registration to patients with poor
      survival on dialysis and no cardiovascular comorbidity.

PMID- 30203619
TI  - Distinguishing histopathologic features of acantholytic dermatoses and the
      pattern of acantholytic hypergranulosis.
AB  - BACKGROUND: Acantholysis can be seen in multiple skin diseases. Adnexal
      acantholysis has been regarded as a feature distinguishing pemphigus vulgaris
      (PV) from acantholytic conditions. METHODS: A retrospective review of the
      histopathologic features of diseases with acantholysis including PV, pemphigus
      foliaceus (PF), Hailey-Hailey disease (HHD), Darier disease (DD), Grover disease,
      and pityriasis rubra pilaris (PRP) was performed. RESULTS: Biopsies of PV (n =
      49), HHD (n = 27), DD (n = 25), Grover disease (n = 65), and PRP (n = 33) showed
      suprabasilar acantholysis. Acantholysis was limited to the lower epidermis in PV
      and PRP, and involved all epidermal layers in HHD, DD, and Grover disease.
      Acantholysis in PF (n = 38) mainly involved the upper epidermis. Follicular
      acantholysis occurred more frequently in PV and PF (P < 0.0001). Eccrine
      acantholysis was found in PV (42%), HHD (18%), PF (13%), and DD (4%). Grover
      disease, DD, and HHD had greater dyskeratosis (P < 0.0001). Neutrophils were more
      common in PV, PF, and HHD, while eosinophils were more common in Grover disease
      and DD. A pattern termed acantholytic hypergranulosis occurred predominantly in
      PF. CONCLUSION: Adnexal acantholysis does not reliably distinguish PV from PF.
      The level of acantholysis, degree of dyskeratosis, and acantholytic
      hypergranulosis are distinguishing features between the two types of pemphigus
      and other acantholytic disorders.

PMID- 30203620
TI  - A Prunus persica genome-wide RNA-seq approach uncovers major differences in the
      transcriptome among chilling injury sensitive and non-sensitive varieties.
AB  - Chilling injury represents a major constrain for crops productivity. Prunus
      persica, one of the most relevant rosacea crops, have early season varieties that
      are resistant to chilling injury, in contrast to late season varieties, which
      display chilling symptoms such as mealiness (dry, sandy fruit mesocarp) after
      prolonged storage at chilling temperatures. To uncover the molecular processes
      related to the ability of early varieties to withstand mealiness, postharvest and
      genome-wide RNA-seq assessments were performed in two early and two late
      varieties. Differences in juice content and ethylene biosynthesis were detected
      among early and late season fruits that became mealy after exposed to prolonged
      chilling. Principal component and data distribution analysis revealed that cold
      stored late variety fruit displayed an exacerbated and unique transcriptome
      profile when compared to any other postharvest condition. A differential
      expression analysis performed using an empirical Bayes mixture modeling approach
      followed by co-expression and functional enrichment analysis uncover processes
      related to ethylene, lipids, cell wall, carotenoids and DNA metabolism, light
      response, and plastid homeostasis associated to the susceptibility or resistance
      of P. persica varieties to chilling stress. Several of the genes related to these
      processes are in quantitative trait loci (QTL) associated to mealiness in P.
      persica. Together, these analyses exemplify how P. persica can be used as a model
      for studying chilling stress in plants.

PMID- 30203621
TI  - Synthesis and Charge-Transporting Properties of Dibenzothiphene Dioxide-Based
      Polysiloxanes.
AB  - We designed and synthesized a dibenzothiphene dioxide-based homopolysiloxane,
      PDBTSi, and a carbazole-dibenzothiophene dioxide alternating copolysiloxane,
      PCzSi-alt-PDBTSi, respectively. Both PDBTSi and PCzSi-alt-PDBTSi possess an
      improved solubility, good film-forming ability and extremely high thermal
      stability due to introduction of polysiloxane main chains. Meanwhile, PDBTSi and
      PCzSi-alt-PDBTSi exhibit high triplet energy levels of 2.95 eV and 3.05 eV,
      respectively. Furthermore, PDBTSi possesses good electron-transporting property
      with an electron mobility of 1.02*10-4  cm2  V-1  s-1 and a relatively balanced
      hole mobility of 8.76*10-5  cm2  V-1  s-1 . In contrast, PCzSi-alt-PDBTSi
      exhibits an electron mobility of 4.65*10-5  cm2  V-1  s-1 and a hole mobility of
      1.17*10-4  cm2  V-1  s-1 . Therefore, our results here provide a feasible
      strategy to obtain solution-processed polysiloxane materials with high and
      balanced electron- and hole-transporting properties.

PMID- 30203622
TI  - Evidence-based dentistry or meta-analysis illness? A commentary on current
      publishing trends in the field of temporomandibular disorders and bruxism.
AB  - The field of temporomandibular disorders (TMDs) and bruxism research has recently
      witnessed a publishing trend leaning towards an overuse of systematic reviews
      (SRs) that contribute little or nothing to current knowledge. The majority of
      these seem to be more methodological exercises than manuscripts prepared to
      provide clinicians and researchers with up-to-date information to advance
      knowledge. In addition, given the increasing number of researchers who have been
      reviewing the dental literature on various topics without seemingly having any
      specific clinical or scientific background in the topic under review, the
      ultimate value of some SRs is questionable. Some of them end up producing meta
      analyses (MAs) to give "numbers" (eg, risk measures and strength of association)
      that do not have a biological basis, due to the clinical heterogeneity of the
      articles being reviewed. Based on the above, the present commentary discusses
      this ongoing publishing trend that is affecting the TMD and bruxism field, which
      does not align well with the core principles of evidence-based dentistry (EBD).
      Ideally, EBD should be derived from a combination of literary, clinical and
      patient-centred information, but relying only on the bibliographic aspects could
      potentially expose less expert clinicians and other readers who merely browse the
      literature to incomplete, misdirected or even incorrect conclusions.

PMID- 30203623
TI  - Clinical implications of molecular markers in acute myeloid leukemia.
AB  - The recently updated World Health Organization (WHO) Classification of myeloid
      neoplasms and leukemia reflects the fact that research in the underlying
      pathogenic mechanisms of acute myeloid leukemia (AML) has led to remarkable
      advances in our understanding of the disease. Gene mutations now allow us to
      explore the enormous diversity among cytogenetically defined subsets of AML,
      particularly the large subset of cytogenetically normal AML. Despite the progress
      in unraveling the tumor genome, only a small number of recurrent mutations have
      been incorporated into risk-stratification schemes and have been proven to be
      clinically relevant, targetable lesions. We here discuss the utility of molecular
      markers in AML in prognostication and treatment decision making, specifically
      highlighting the aberrations included in the current WHO classification.

PMID- 30203624
TI  - Insular-limbic dissociation to intra-epidermal electrical Adelta activation: A
      comparative study with thermo-nociceptive laser stimulation.
AB  - Intra-epidermal electrical stimulation (IEES) has been shown to activate
      selectively Adelta fibers subserving spinothalamic-mediated sensations. Owing to
      electrically induced highly synchronous afferent volleys, IEES induces Adelta
      mediated evoked potentials at nonpainful intensities, contrasting with thermo
      nociceptive laser pulses which entail painful pricking sensations. Here, we
      recorded intracortical responses from sensory and limbic-cognitive regions of
      human subjects in response to IEE and laser stimuli, in order to test the
      hypothesis that IEES could dissociate the sensory from nonsensory networks of
      nociceptive processing. Intracortical evoked potentials were obtained in 11
      epileptic patients with stereotactically implanted electrodes in sensory regions
      receiving spinothalamic afferents (posterior insula), limbic regions receiving
      spino-parabrachial input (amygdalar nucleus), and high-order affective-cognitive
      regions (anteromedial frontal cortex, including perigenual anterior cingulate and
      rostromedial prefrontal areas). Responses in the sensory posterior insula were of
      similar amplitude and latency to IEE and laser stimuli (after accounting for heat
      transduction time of laser), and consistent in both cases with spinothalamic
      activation. However, responses to IEES in the amygdala and the anteromedial
      frontal regions were inconsistent and significantly smaller compared to those
      evoked to the laser stimulation. Thus, IEES can effectively activate the
      spinothalamic-sensory system with little recruitment of affective-motivational
      networks, including those triggered by spino-parabrachio-amygdalar projections.
      The fact that identical sensory responses were associated to either painful or
      nonpainful percepts underscores that subjective pain perception is not solely
      dependent on the sensory recruitment, but rather on the combined activation of
      sensory, limbic and cognitive areas with precise spatiotemporal relations.

PMID- 30203625
TI  - What factors affect the duration of treatment with diphenylcyclopropenone
      immunotherapy for common warts?

PMID- 30203626
TI  - Pediatric transplantation case conference: Update on cytomegalovirus.
AB  - The prevention and management of cytomegalovirus (CMV) remain challenging in
      children who have undergone solid organ transplantation, despite the availability
      of effective antiviral medications and sensitive diagnostic assays. The primary
      objective of this invited commentary is to provide an updated and
      multidisciplinary approach to persistently challenging CMV cases that commonly
      occur in pediatric transplantation candidates and recipients, including cases for
      which published data are frequently lacking.

PMID- 30203627
TI  - Association of levels of interleukin 17 and T-helper 17 count with symptom
      severity and etiology of chronic heart failure: a case-control study.
AB  - AIM: To assess the association between the levels of interleukin 17 (IL-17) and T
      helper 17 count and symptom severity and etiology of chronic heart failure.
      METHODS: This single-center prospective case-control study, conducted from
      December 1, 2015 to January 1, 2017 in Tehran Heart Center, evaluated gene
      expression of IL-17, relative count of (CD4+IL17+) Th17 cells and CD4+ helper T
      cells in peripheral blood mononuclear cells of 42 patients with CHF and 42
      matched controls. A multiple regression model assessed the predictors of
      peripheral IL-17 expression and Th17 count in patients with CHF. RESULTS: IL-17
      expression was increased in patients with CHF, both at baseline and after
      stimulation. IL-17 and Th17 counts were higher in patients with advanced New York
      Heart Association (NYHA) functional class (class IV) than in controls and
      patients with class I. Th17 cell population expanded in patients with CHF, more
      prominently in patients with class IV than in controls and patients with class I,
      regardless of the ischemic or non-ischemic CHF origin. Multiple regression model
      showed that NYHA was the only meaningful predictor of IL-17 levels and Th17
      count. CONCLUSION: We demonstrated the lymphocytic origin of IL-17 production in
      advanced CHF and the ability of disease severity to predict IL-17 levels. Oxford
      Centre for Evidence-based Medicine level of evidence: 3.

PMID- 30203628
TI  - Prognostic value of lactates in relation to gas analysis and acid-base status in
      patients with pulmonary embolism.
AB  - AIM: To assess the prognostic value of lactate level for mortality in patients
      with pulmonary embolism (PE) and Pulmonary Embolism Severity Index (PESI) I-III
      and its independence of gas-analysis parameters and acid-base status. METHODS:
      This prospective observational study was conducted at the University Clinical
      Hospital Mostar from 2013 to 2017. On the first day after PE diagnosis, 1.5 mL of
      arterial blood was collected from 103 patients with PE. Partial pressure of
      oxygen in arterial blood, partial pressure of carbon dioxide in arterial blood,
      blood pH value, concentration of bicarbonates in arterial blood (HCO3-), base
      deficit, and oxygen saturation were analyzed. Lactate levels were assessed using
      blood samples taken from the cubital vein. Logistic regression analysis was used
      to assess the predictive value of gas-analysis variables, lactate level, PESI
      score, age, and sex for in-hospital death due to PE. RESULTS: The mortality in
      the group of PE patients was 19.1% (18 of 103 patients). Lactate level was an
      independent predictor of mortality (P=0.002, odds ratio 0.06). HCO3- was also
      found to be a significant predictor (P=0.022, odds ratio 2.4). Lactates were
      independent of other variables. Other gas-analysis parameters were not
      significant predictors of mortality. CONCLUSION: In PE patients at low
      intermediate risk of mortality (PESI I-III), lactate level was associated with a
      short-term mortality, independently of other gas-analytic parameters. Oxford
      Centre for Evidence-based Medicine level of evidence: 2.

PMID- 30203629
TI  - Comparison of ego strength between aggressive and non-aggressive alcoholics: a
      cross-sectional study.
AB  - AIM: To determine the differences between aggressive and non-aggressive
      alcoholics in sociodemographic and clinical characteristics and ego strength.
      METHODS: This cross-sectional study included 111 aggressive and 123 non
      aggressive male alcoholics aged between 25 and 60 years who were admitted to the
      Department for Alcoholism, University Psychiatric Hospital Vrapce, Zagreb,
      Croatia, from January to December 2016. All participants met the diagnostic
      criteria for alcohol dependence according to the Croatian Mini International
      Neuropsychiatric Interview (MINI), 4th revised edition of Diagnostic and
      Statistical Manual of Mental Disorders, and the International Classification of
      Diseases. Participants were clinically assessed by an experienced psychiatrist
      using a clinical interview, MINI, Questionnaire from the Brown-Goodwin Lifetime
      History of Aggression, and Ego Identity Scale (EIS) according to Erikson. A
      clinical psychologist performed cognitive function measurements. EIS scores were
      analyzed using one-way analysis of variance. RESULTS: In comparison with non
      aggressive alcoholics, aggressive alcoholics were more often divorced,
      unemployed, hospitalized, and first treated for alcoholism at an earlier age
      (P<0.05 for all). They more frequently experienced depression (42.4% vs 19.4%,
      P=0.013) and attempted suicide (34.7% vs 6.2%, P=0.003), achieved a lower level
      of maturity at the second stage of psychosocial development related to shame and
      doubt (14.0+/-4.1 vs 17.4+/-3.7, P=0.013) and at the fourth stage related to
      inferiority (13.1+/-6.8 vs 18.1+/-9.3, P=0.011), and had lower total EIS score
      (75.8+/-20.4 vs 85.2+/-21.5, P<0.012) than non-aggressive alcoholics. CONCLUSION:
      Aggressive alcoholics had weaker ego-strength than non-aggressive alcoholics,
      experienced more depressive reactions and suicide attempts, and showed poorer
      psychosocial functioning. Oxford Centre for Evidence-based Medicine level of
      evidence: 3*.

PMID- 30203631
TI  - Digital mediators as key enablers of navigation toward health in knowledge
      landscapes.

PMID- 30203630
TI  - The relationship among psychopathology, religiosity, and nicotine dependence in
      Croatian war veterans with posttraumatic stress disorder.
AB  - AIM: To examine relationships among combat exposure, posttraumatic stress
      disorder (PTSD) symptoms, depression, suicidality, nicotine dependence, and
      religiosity in Croatian veterans. METHODS: This cross-sectional study used Combat
      Exposure Scale (CES) to quantify the stressor severity, PTSD Checklist 5 (PCL) to
      quantify PTSD severity, Duke University Religion Index to quantify religiosity,
      Montgomery Asberg (MADRS) and Hamilton Depression (HAM-D) rating scales to
      measure depression/suicidality, and Fagerstrom Test for Nicotine Dependence to
      assess nicotine dependence. Zero-order correlations, cluster analysis,
      multivariate regression, and mediation models were used for data analysis.
      RESULTS: Of 69 patients included, 71% met "high religiosity" criteria and 29% had
      moderate/high nicotine dependence. PTSD was severe (median PCL 71), depression
      was mild/moderate (median MADRS 19, HAM-D 14), while suicidality was mild. A
      subset of patients was identified with more severe PTSD/depression/suicidality
      and nicotine dependence (all P<0.001). Two "chains" of direct and indirect
      independent associations were detected. Higher CES was associated with higher
      level of re-experiencing and, through re-experiencing, with higher negativity and
      hyperarousal. It also showed "downstream" division into two arms, one including a
      direct and indirect association with higher depression and lower probability of
      high religiosity, and the other including associations with higher suicidality
      and lower probability of high nicotine dependence. CONCLUSIONS: Psychopathology,
      religiosity, and nicotine dependence are intertwined in a complex way not
      detectable by simple direct associations. Heavy smoking might be a marker of
      severe PTSD psychopathology, while spirituality might be targeted in attempts of
      its alleviation. Oxford Centre for Evidence-based Medicine level of evidence: 3.

PMID- 30203632
TI  - Photobiomodulation therapy improves multilineage differentiation of dental pulp
      stem cells in three-dimensional culture model.
AB  - Photobiomodulation therapy (PBM) has shown positive effects on stem cell
      differentiation in monolayer cell culture model, but little is known about its
      effect on three-dimensional (3-D) agarose gel culture. This study evaluated the
      PBM effect of human dental pulp stem cells (hDPSCs) differentiation and
      phosphatase alkaline activity (ALP) using an agarose 3-D model under different
      nutritional conditions. hDPSCs were characterized and seeded on a 0.3% agarose
      gel layer with different media (osteogenic, adipogenic, chondrogenic) and were
      assigned into four groups: control 10% fetal bovine serum (FBS), control 5% FBS,
      PBM 10% FBS, and PBM 5% FBS. Irradiation was performed with continuous-wave
      InGaAlP laser, 660 nm, 100 mW, 3,3  J  /  cm2, spot size 0.3  cm2, 10 s of
      exposure time, and 1 J of energy per point with 6-h interval between sessions.
      All groups were evaluated at 7 and 14 days. ALP assay was performed to analyze
      the deposition of mineralized tissue. At 7 days, PBM 5% FBS group presented
      better stimulation in osteogenic and adipogenic differentiation compared with
      control. After 14 days, hDPSCs cultured in 3-D exhibited osteogenic, adipogenic,
      and chondrogenic differentiation; furthermore, compared to control, PBM
      significantly stimulated all differentiation processes (p  <  0.05). It can be
      concluded that hDPSCs cultured in 3-D agarose associated to PBM could be a
      promising tool for tissue engineering applications.

PMID- 30203633
TI  - The value of exfoliative cell cytology in the diagnosis of exudative pleural
      effusions.
AB  - The sensitivity and specificity of exfoliative cell cytology for the diagnosis of
      exudative pleural effusions varies widely according to the etiologic causes. The
      aim of this study is to assess the diagnostic value of exfoliative cell cytology
      for the identification of exudative pleural effusions. This is a retrospective
      study of the patients with an exudative pleural effusion admitted at our clinic
      in the last twenty years. We have conducted the clinical, the cytological
      findings, and the diagnostic results of six hundred patients from hospital
      records.  Male to female ratio was 2.2:1 with a mean age of 42.8 years (range 18
      78 years) among the patients. Samples were processed and evaluated according to
      the standard methods. Cytology results were reviewed and the patients were
      stratified according to the final diagnosis of their disease. Of the six hundred
      exudative effusions, 240 were malignant on exfoliative cytology pleural fluid
      alone. Adenocarcinoma was the most common type of malignancy. Tuberculosis was
      the second most frequent etiology for the exudative effusions followed by
      infection and collagen vascular diseases. Diagnostic accuracy of cytology showed
      a good correlation with the final diagnosis with an overall 70.1% sensitivity,
      62.5% specificity, and a 95.9% positive predictive value for all exudative
      pleural effusions. Cytologic examination of the pleural fluid is a simple non
      invasive procedure as the initial step for the diagnostic work up of patients
      with a pleural effusion.  Exfoliative cytology provides high a final diagnostic
      yield for the identification of an exudative pleural effusion etiology.
      Furthermore, cytologic analysis leads the clinician into the correct diagnostic
      pathway as the most informative laboratory tool even when it was not diagnostic
      by itself for equivocal cases.

PMID- 30203634
TI  - An unexpected complication of a percutaneous coronary angioplasty.
AB  - Takotsubo cardiomyopathy (TCM) is characterized by transient ventricular
      dysfunction, classically in its apical and mid segments, in the absence of
      coronary lesions, and is often observed after intense stressful events and
      occasionally associated to an acute medical illness. We describe a case of TCM
      associated with coronary artery disease and triggered by a percutaneous coronary
      angioplasty. This case highlights the concept that a medical procedure can lead,
      in certain conditions, to TCM and provides new interesting insights on the
      pathophysiology of coronary syndromes.

PMID- 30203635
TI  - Exogenous lipoid pneumonia associated with oil pulling: Report of two cases.
AB  - Two ladies with history of carcinoma of tongue presenting with un-resolving
      pneumonia were ultimately diagnosed to have lipoid pneumonia, and both were
      subsequently found to be associated with the practice of oil pulling which is a
      popular complementary therapy. Apart from cessation of oil pulling, they were
      treated with repeated therapeutic lobar broncho-alveolar lavage. despite the
      potential benefits of oil pulling on oral health, people especially those at risk
      of aspiration, should be properly informed of this potential risk when
      considering this form of complementary therapy.

PMID- 30203636
TI  - The role of psychopathology in perceiving, reporting and treating intermittent
      claudication: a systematic review.
AB  - INTRODUCTION: The aim of this systematic review is to investigate the association
      between mental health and intermittent claudication (IC) perception, reporting
      and treatment in subjects with peripheral artery disease (PAD). EVIDENCE
      ACQUISITION: Literature searches of experimental and observational studies
      published until February 1st, 2016 were conducted using the following electronic
      databases: Medline/PubMed and Embase. The selection criteria for the studies
      included a population of patients diagnosed with peripheral artery disease who
      reported symptoms of intermittent claudication and were assessed for any
      psychopathological states (depression, anxiety, mood and personality disorders),
      which in turn were analyzed with regard to the following: IC severity, symptom
      perception and reporting, patients' quality of life, treatment compliance and its
      effectiveness. The risk of bias was assessed using Cochrane Collaboration's tool
      and the Newcastle Ottawa Scales. The strength of recommendations was graded
      according to GRADE system. EVIDENCE SYNTHESIS: The literature search identified
      1598 citations, of which 13 studies with varying risk of bias were included in
      the review. Depression, anxiety, and personality types were described in more
      than 800 patients with peripheral arterial disease who suffered from intermittent
      claudication. With regard to IC perception and reporting, individuals with higher
      levels of depression had lower levels of pain acceptance, were more dissatisfied
      with their function and control over function and had a poorer quality of life.
      In the case of the type D personality, the results were not consistent. Studies
      assessing the influence of psychopathology on IC severity and treatment also
      showed discrepant results. Some studies indicated no differences between type D
      and non-type D patients with regard to the Ankle Brachial Index as well as pain
      free (PFWD) and maximal walking distances (MWD). On the other hand, others
      revealed that type D and depressed patients terminated 6MWT prematurely due to
      the onset of symptoms and experienced a greater annual decline in 6-minute walk
      distance, fast walking velocity and short physical performance battery. With
      regard to treatment adherence, patients with no mental problems made the best
      recoveries. Hostility, aggressiveness and affect-liability were the greatest
      obstacles to compliance. CONCLUSIONS: Mental disorders might influence the way in
      which the symptoms of the disease are reported, coped with, and treated. However,
      the results of the review preclude recommending a routine psychological
      examination as one of basic diagnostic procedures in patients with peripheral
      artery disease suffering from IC.

PMID- 30203637
TI  - Finite element analysis in symptomatic and asymptomatic abdominal aortic
      aneurysms for aortic disease risk stratification.
AB  - BACKGROUND: Advanced biomechanical models can provide additional information
      concerning rupture risk in abdominal aortic aneurysms (AAA). Here we evaluated
      the predictive value of finite element analysis (FEA) to assess AAA rupture risk.
      METHODS: In a case-control study, we compared FEA parameters in a group of
      symptomatic AAA (sAAA) patients, considered as a high risk of rupture group, with
      FEA parameters in asymptomatic AAA patients (aAAA). RESULTS: We included 15 sAAA
      and 28 aAAA patients matched for age- and maximum diameter diagnosed with
      infrarenal non-ruptured AAA at our centre between 2009 and 2013. Mean (standard
      deviation) age was 75 (69) years and maximum diameter was 77 (17) mm. Peak wall
      stress (PWS) was significantly higher in sAAA patients than in aAAA patients
      (354.3 (139.6) kPa vs 248.6 (81.9) kPa;P=.001). The C statistic for the ROC curve
      based on PWS was 0.748 [95% CI 0.592-0.903; P=.008]. CART analysis classified
      patients into high and low PWS groups. The high-PWS group (>305.15 kPa; n=15) had
      a higher incidence of sAAA (33.3% aAAA, 66.7% sAAA) than the low-PWS-group
      (<=305.15 kPa; n=28. 82.1% aAAA, 17.9% sAAA). CONCLUSIONS: In conclusion, PWS was
      significantly higher in sAAA patients. Measuring PWS may help estimate the
      individual rupture risk in patients with AAA, but larger studies are needed to
      confirm our results.

PMID- 30203638
TI  - Renal function after abdominal aortic aneurysm repair in patients with baseline
      chronic renal insufficiency: open vs. endovascular repair.
AB  - BACKGROUND: The aim of this study is to analyze renal function impairment (RFI)
      after abdominal aortic aneurysm (AAA) repair in patients with preoperative
      chronic kidney disease (CKD). METHODS: Retrospective cohort study of patients
      with CKD undergoing elective AAA repair between 2008-2015, dividing the sample
      into two groups: open repair (OR) and endovascular repair (EVAR). The primary
      outcome was RFI defined by the RIFLE scale, studying Risk (1.5-fold increase in
      Cr or GFR decline >25% compared to baseline) and kidney injury (doubling of Cr or
      GFR decline >50%). RESULTS: Seventy-five patients (OR=29, EVAR=46). Baseline
      characteristics for OR and EVAR were similar except for age (70.4 vs. 77.2 years;
      P<0.001), coronary artery disease (31% vs. 56.5%; P=0.04), neck length (12.3 vs.
      22.7 mm; P=0.001) and baseline GFR (40.6 vs. 36.9 mL/min; P=0.03). There were no
      inter-group differences in postoperative RFI: Risk of RFI 13.8% OR vs. 13% EVAR
      and kidney Injury 6.9% vs. 0% (P=0.19). There were also no differences in RFI at
      one year. Comparing GFR and Cr after surgery and at 12 months to baseline values,
      the OR group presented a significant postoperative decline in GFR compared to
      EVAR group (-3.8% vs. 11.1%; P=0.03), which had recovered at one-year follow-up
      (16.6% vs. 9.5%; P=0.43), while EVAR group presented with a tendency toward
      increased Cr during follow-up (-9.2% vs. 2.2%; P=0.08). Multivariate analysis did
      not identify independent RFI prognostic factors. CONCLUSIONS: Both techniques can
      be used safely in patients with CKD and baseline CKD is not a limiting factor for
      either technique. RFI is rare and transient in both groups.

PMID- 30203639
TI  - Endovascular treatments for type Ib endoleaks after aorto-iliac aneurysms
      exclusion: mid-term results.
AB  - BACKGROUND: To report early and mid-term results of endovascular treatments for
      type Ib endoleaks (IbEL) after endovascular aneurysm repair (EVAR) for aorto
      iliac aneurysms (AAA). METHODS: Patients with IbEL after EVAR were
      retrospectively analyzed. Cases of IbEL treated in two centers from January 2009
      to February 2017 were considered. Patients' demographics and comorbidities,
      interval between EVAR and IbEL diagnosis, type of endograft, site of sealing,
      oversize and length of iliac sealing zone, type of IbEL treatment were collected.
      Main endpoints were freedom from IbEL recurrence and freedom from reintervention.
      RESULTS: Thirty-five IbEL were treated in 29 patients (mean age: 76+/-7years;
      male: 100%). Mean time between EVAR and IbEL detection was 43+/-30months. IbEL
      was symptomatic in 4 (14%) and bilateral in 6 (21%). Endograft was bifurcated in
      26 patients (90%) and aorto-uniiliac in 3 (10%). Distal landing zone was achieved
      in common and external iliac artery in 33 (94%) and 2 cases (6%), respectively.
      Mean oversize of endograft limb was 11+/-9%, mean length of sealing zone was 22+/
      15 mm. Endovascular treatments included: 34 iliac extensions (8 cases [24%] with
      hypogastric artery coverage), and 1 embolization. Concomitant embolization of
      hypogastric artery was performed in 3 (9%) cases. Technical success was 100%,
      with no procedure-related complication. Considering patients with hypogastric
      exclusion, buttock claudication developed in 2/8 cases (25%). Mean follow-up was
      20+/-19 months. Freedom from IbEL was 100% and no reintervention was necessity
      for IbEL during follow-up. At 12, 24 and 36 months, survival was 88%, 82% e 61%,
      respectively, with no IbEL-related death. CONCLUSIONS: IbEL can be easily managed
      by endovascular means, typically with distal extensions with landing zones in the
      common or external iliac artery. Mid-term results are favourable, with no
      recurrent IbEL or reintervention.

PMID- 30203640
TI  - Treatment protocol on stasis edema in poorly mobile nursing home patients.
AB  - BACKGROUND: Prolonged immobility in the sitting position in the elderly is known
      to produce venous stasis with leg edema and possible skin changes. METHODS: The
      authors have tested a treatment protocol in 30 patients to quantify the reduction
      of volume caused by an adjustable compression Velcro(r) wrap (Circaid
      Juxtalite(r), medi GmbH, Bayreuth, Germany) after 15 days and to compare its
      effect on the leg volume for the next 15 days with 15- to 20-mmHg compression
      stockings (CS). RESULTS: The authors noted a volume decrease between T0 and T15
      by 10.8% (52 legs) under Circaid Juxtalite(r). At T30, they observed a non
      significant difference between Circaid Juxtalite(r) (-1%) and the CS (1.3%).
      CONCLUSIONS: A Velcro(r) adjustable compression wrap (Circaid Juxtalite(r)) is
      efficient in reducing stasis edema in the elderly. Stabilization of the leg
      volume with the use of 15-20 mmHg CS suggests that a high pressure to maintain
      results is not required to maintain results.

PMID- 30203641
TI  - C0a and C0s patients: potential benefits for an unclear population.

PMID- 30203642
TI  - Design Synthesis of ITE Zeolite Using Nickel-Amine Complex as an Efficient
      Structure-Directing Agent.
AB  - Modern methodologies for synthesizing zeolites typically involve the employment
      of costly organic structure-directing agents. Herein, we report the design
      synthesis of aluminosilicate zeolite with ITE structure using an inexpensive
      nickel-amine complex (nickel-pentaethylenexamine) as a novel structure-directing
      agent. Characterizations including X-ray diffraction, scanning electron
      microscopy, N2 sorption isotherms, and 27Al magic-angle spinning NMR techniques
      show that the ITE zeolite has high crystallinity, perfect crystals, large surface
      area, and abundant aluminum species in the framework. More importantly, catalytic
      tests on the hydrogenation of CO2 into methane show that the Ni-ITE zeolite
      exhibits better catalytic performance than aluminosilicate-supported and silica
      supported nickel catalysts. Obviously, the use of nickel-amine complex offers an
      alternative and facile way to synthesize aluminosilicate zeolites.

PMID- 30203643
TI  - Tetrathiafulvalene (TTF)-Annulated Calix[4]pyrroles: Chemically Switchable
      Systems with Encodable Allosteric Recognition and Logic Gate Functions.
AB  - Molecular and supramolecular systems capable of switching between two or more
      states as the result of an applied chemical stimulus are attracting ever
      increasing attention. They have seen wide application in the development of
      functional materials including, but not limited to, molecular and supramolecular
      switches, chemosensors, electronics, optoelectronics, and logic gates. A wide
      range of chemical stimuli have been used to control the switching within bi- and
      multiple state systems made up from either singular molecular entities or
      supramolecular ensembles. In general, chemically triggered switching systems
      contain at least two major functional components that provide for molecular
      recognition and signal transduction, respectively. These components can be
      connected to one another via either covalent or noncovalent linkages. Of
      particular interest are switchable systems displaying cooperative or allosteric
      features. Such advanced control over function is ubiquitous in nature and, in the
      case of synthetic systems, may allow the capture and release of a targeted
      chemical entity or permit the transduction of binding information from one
      recognition site to another. Allosterically controlled complexation and
      decomplexation could also permit the amplification or deamplification of analyte
      specific binding affinity, lead to nonlinear binding characteristics, or permit a
      magnification of output signals. Our own efforts to develop chemically driven
      supramolecular switches, advanced logic gates, and multifunction cascade systems
      have focused on the use of tetrathiafulvalene (TTF) annulated calix[4]pyrroles
      (C4Ps). These systems, TTF-C4Ps, combine several orthogonal binding motifs within
      what are conformationally switchable receptor frameworks. Their basic structure
      and host-guest recognition functions can be controlled via application of an
      appropriate chemical stimulus. Homotropic or heterotropic allosteric molecular
      recognition behavior is often seen. This has allowed us to (1) produce self
      assembled structures, (2) control switching between bi- and multistate
      constructs, (3) generate chemical logic gates performing chemical-based Boolean
      logic operations, (4) create ionically controlled three-state logic systems that
      release different chemical messengers and activate disparate downstream
      reactions, and (5) encode a variety advanced functional operations into what are
      relatively simple molecular-scale devices. Looking to the future, we believe that
      exploiting allosteric control will expand opportunities for supramolecular
      chemists and allow some of the complexity seen in biology to be reproduced in
      simple constructs. Of particular appeal would be a capacity to release chemical
      messengers at will, perhaps after a prior capture and chemical modification step,
      that then encode for further downstream functions as seen in the case of the
      small molecules, such as neurotransmitters and pheromones, used by nature for the
      purpose of intraentity communication. Molecular scale logic devices with
      allosteric functions are thus the potential vanguard of a new area of study
      involving interactions between multiple discrete components with an emphasis on
      functional outcomes.

PMID- 30203644
TI  - Effects of Flange Adsorption Affinity and Membrane Porosity on Interfacial
      Resistance in Carbon Nanotube Membranes.
AB  - We have used nonequilibrium molecular dynamics simulations to investigate the
      transport diffusion of methane, at 300 K and pressures of up to 15 bar, in 30 nm
      long (10, 10) carbon nanotubes (CNTs) held between two flanges mounted at the
      ends to represent the surface layers of an embedding matrix material. Strong
      interfacial resistance to the entry and exit of molecules is found in the 30 nm
      long CNTs, which reduces their permeability by more than 2 orders of magnitude.
      Increasing the adsorption affinity and surface area of the flange reduces the
      interfacial resistance and consequently enhances the methane diffusivity in CNT
      membranes. Curved streamlines near the flange surface make a significant
      contribution to the permeability, even when the adsorption on the matrix surface
      is negligible. We propose a model to calculate the separate components of the
      interfacial resistance, the flange resistance, which increases with increase in
      the membrane porosity, and the entrance-exit resistance, which is independent of
      the membrane porosity. While the flange resistance accounts for the reduction of
      interfacial resistance with decrease in the membrane porosity, the entrance-exit
      resistance is responsible for the reduction of interfacial resistance with
      increase in the flange adsorption affinity. The flange resistivity demonstrates a
      complex dependency on the flange adsorption affinity, which is attributed to the
      competition between the enhanced adsorption and the enhanced migration time of
      the molecules on the flange. It is concluded that the embedding matrix adsorption
      affinity and membrane porosity separately play critical roles in determining the
      interfacial resistance and permeability in CNT membranes. Our simulation results
      can help reduce the interfacial resistance and improve the permeance in CNT
      membranes by appropriate choice of intertube spacing and flange material and are
      readily applied to all nanoporous membranes with a passive matrix.

PMID- 30203646
TI  - Zeolitic Imidazolate Framework Membranes for Organic Solvent Nanofiltration: A
      Molecular Simulation Exploration.
AB  - Organic solvents are intensively used in chemical and pharmaceutical industries.
      Their separation and recovery account for a significant portion of energy
      consumption and capital cost in many industrial processes. In this study, three
      microporous crystalline zeolitic imidazolate frameworks (ZIF-25, ZIF-71, and ZIF
      96) are investigated as organic solvent nanofiltration (OSN) membranes by
      molecular simulations. The fluxes of five solvents (methanol, ethanol, acetone,
      acetonitrile, and n-hexane) are predicted. Despite the smallest aperture size
      among the three ZIFs, ZIF-25 exhibits the highest flux for polar solvents
      (methanol, ethanol, acetone, and acetonitrile) because of its hydrophobic nature,
      whereas hydrophilic ZIF-96 shows the highest flux for nonpolar n-hexane. The
      analysis of structural information and interaction energy reveals that the
      solvent-framework interaction is crucial to determine solvent permeation. Good
      correlations between solvent permeances and a combination of solvent properties
      are found. In the presence of a model solute (paracetamol), solvent permeances
      are marginally affected; moreover, the rejection of paracetamol is 100% for the
      three ZIF membranes in all five solvents. This study highlights that the pore
      chemistry, in addition to pore size, plays an important role in solvent
      permeation, and it suggests that ZIFs are potential OSN membranes for the
      recovery of organic solvents.

PMID- 30203645
TI  - Surface-Enhanced Raman Scattering Nanoparticles for Multiplexed Imaging of
      Bladder Cancer Tissue Permeability and Molecular Phenotype.
AB  - Bladder cancer has the highest recurrence rate of all cancers due in part to
      inadequate transurethral resection. Inadequate resection is caused by the
      inability of cystoscopes to detect invisible lesions during the resection
      procedure. To improve detection and resection of nonmuscle invasive bladder
      cancer, we quantified the ability of a surface-enhanced Raman nanoparticle and
      endoscope system to classify bladder tissue as normal or cancerous. Both antibody
      based (active) and tissue permeability-based (passive) targeting mechanisms were
      evaluated by topically applying nanoparticles to ex vivo human bladder tissue
      samples. Multiplexed molecular imaging of CD47 and Carbonic Anhydrase 9 tumor
      proteins gave a receiver operating characteristic area under the curve (ROC AUC
      of 0.93 (0.75, 1.00). Furthermore, passively targeted nanoparticles enabled
      tissue classification with an ROC AUC of 0.93 (0.73, 1.00). Passively targeted
      nanoparticles penetrated 5-fold deeper and bound to tumor tissue at 3.3-fold
      higher concentrations in cancer compared to normal bladder urothelium, suggesting
      the existence of an enhanced surface permeability and retention effect in human
      bladder cancer.

PMID- 30203647
TI  - Toward Understanding the Chemistry and Biology of 1-Deoxy-d-xylulose 5-Phosphate
      (DXP) Synthase: A Unique Antimicrobial Target at the Heart of Bacterial
      Metabolism.
AB  - Antibiotics are the cornerstone of modern healthcare. The 20th century discovery
      of sulfonamides and beta-lactam antibiotics altered human society immensely.
      Simple bacterial infections were no longer a leading cause of morbidity and
      mortality, and antibiotic prophylaxis greatly reduced the risk of infection from
      surgery. The current healthcare system requires effective antibiotics to
      function. However, antibiotic-resistant infections are becoming increasingly
      prevalent, threatening the emergence of a postantibiotic era. To prevent this
      public health crisis, antibiotics with novel modes of action are needed.
      Currently available antibiotics target just a few cellular processes to exert
      their activity: DNA, RNA, protein, and cell wall biosynthesis. Bacterial central
      metabolism is underexploited, offering a wealth of potential new targets that can
      be pursued toward expanding the armamentarium against microbial infections.
      Discovered in 1997 as the first enzyme in the methylerythritol phosphate (MEP)
      pathway, 1-deoxy-d-xylulose 5-phosphate (DXP) synthase is a thiamine diphosphate
      (ThDP)-dependent enzyme that catalyzes the decarboxylative condensation of
      pyruvate and d-glyceraldehyde 3-phosphate (d-GAP) to form DXP. This five-carbon
      metabolite feeds into three separate essential pathways for bacterial central
      metabolism: ThDP synthesis, pyridoxal phosphate (PLP) synthesis, and the MEP
      pathway for isoprenoid synthesis. While it has long been identified as a target
      for the development of antimicrobial agents, limited progress has been made
      toward developing selective inhibitors of the enzyme. This Account highlights
      advances from our lab over the past decade to understand this important and
      unique enzyme. Unlike all other known ThDP-dependent enzymes, DXP synthase uses a
      random-sequential mechanism that requires the formation of a ternary complex
      prior to decarboxylation of the lactyl-ThDP intermediate. Its large active site
      accommodates a variety of acceptor substrates, lending itself to a number of
      alternative activities, such as the production of alpha-hydroxy ketones,
      hydroxamates, amides, acetolactate, and peracetate. Knowledge gained from
      mechanistic and substrate-specificity studies has guided the development of
      selective inhibitors with antibacterial activity and provides a biochemical
      foundation toward understanding DXP synthase function in bacterial cells.
      Although it is a promising drug target, the centrality of DXP synthase in
      bacterial metabolism imparts specific challenges to assessing antibacterial
      activity of DXP synthase inhibitors, and the susceptibility of most bacteria to
      current DXP synthase inhibitors is remarkably culture-medium-dependent. Despite
      these challenges, the study of DXP synthase is poised to reveal the role of DXP
      synthase in bacterial metabolic adaptability during infection, ultimately
      providing a more complete picture of how inhibiting this crucial enzyme can be
      used to develop novel antibiotics.

PMID- 30203648
TI  - Porous Shape-Persistent Organic Cage Compounds of Different Size, Geometry, and
      Function.
AB  - The interest in shape-persistent organic cages is nearly as old as the interest
      in supramolecular chemistry. In the beginning, organic cages have often been
      synthesized in a stepwise manner, which is not only laborious but very often also
      accompanied by low overall yields. In 1988, MacDowell published the one pot high
      yielding synthesis of [2 + 3] imine cages based on TREN and aromatic dialdehydes,
      exploiting the reversible condensation of amines and aldehydes to  imines, which
      was later used by others to make even larger cages on the basis of
      resorcinarenes. In 2008, the synthesis and characterization of an adamantoid [4 +
      6] imine cage by condensation of a C3 v-symmetric triaminotriptycene and
      commercially available 4- tert-butyl salicyldialdehyde was introduced by the
      author, which was the ignition of our group activities in this research area. In
      2011, we published the first gas-sorption data for this [4 + 6] imine cage: with
      a measured specific surface area of SABET = 1377 m2/g according to the model of
      Brunauer-Emmett-Teller (BET) this was twice as high as for the reported smaller
      cages of Cooper. For a second desolvated polymorph of the same cage, an even
      higher SABET = 2071 m2/g was determined; still one of the highest surface areas
      until date for porous organic molecular materials. Subsequently, the influence of
      the substituent in 4-position of the salicyldialdehyde for the reaction to [4 +
      6] imine cages was investigated as well as the role of the phenolic hydroxyl
      group. It turned out that the phenolic hydroxyl group is crucial as directing
      group to increase the formation of the cage as well as stabilize the structure by
      cyclic six-membered intramolecular hydrogen bonds. The concept was extended to
      other imine-based cages of different geometry and size. For instance, a [4 + 4]
      cubic structure from triptycene trissalicylaldehyde and triptycene triamine was
      accessible as an amorphous insoluble solid, able to adsorb 18.2 wt % CO2 at
      ambient conditions. To gain further insight into the structural needs of the
      molecular precursors, rigidity and preorientation of reacting sites were
      investigated on prismatic [2 + 3] and truncated tetrahedral [4 + 4] imine cages,
      showing that rigidity and preorientation is beneficial or even crucial for cage
      formation. Furthermore, chiral self-sorting was studied on the basic of racemic
      triamines. Besides imine condensation, we explored the reversible formation of
      boronic esters from boronic acids and diols. Triptycene tetraol with its 120
      degrees  angle between the aromatic units has been used in the condensation with
      benzene triboronic acid to achieve a large cuboctahedral [12 + 8] cage with pore
      dimensions of 2 nm, which are by IUPAC definition mesoporous. After activation
      the measured specific surface area was SABET = 3758 m2/g, a number rarely
      achieved even for other porous compounds such as threedimensional framework
      materials. Smaller tetrahedral [4 + 6] boronic ester cages were synthesized too.
      These cages show a selective gas sorption with preference of saturated
      hydrocarbon ethane over ethylene and acetylene. What distinguishes porous
      materials derived from molecular cages from three-dimensional frameworks or
      networks the most is their solubility; thus, the cages are soluble porous units
      (SPUs) in a broader sense. Taking advantage of this, [4 + 6] imine cages were
      postfunctionalized in solution to change the gas sorption properties in the
      crystalline state. Furthermore, cage solutions were spray-coated onto quartz
      crystal microbalances to enhance affinity and selectivity for sensing of airborne
      analytes. In this Account, the contributions from our lab on porous organic cages
      are presented.

PMID- 30203649
TI  - Accessing alpha-Arylated Nitriles via BF3.OEt2 Catalyzed Cyanation of para
      Quinone Methides Using tert-Butyl Isocyanide as a Cyanide Source.
AB  - BF3.OEt2 catalyzed 1,6-conjugate addition of tert-butyl isocyanide to para
      quinone methides and fuchsones for the synthesis of alpha-diaryl and alpha
      triaryl nitriles has been reported. This protocol allows alpha-diaryl- and alpha
      triaryl nitriles to be accessed in good to excellent yields and with a broad
      substrate scope, which could be further functionalized to give a versatile set of
      products. This is the first example wherein tert-butyl isocyanide has been used
      as a cyanide source for the 1,6-conjugate addition.

PMID- 30203650
TI  - Alkyl Isosteres.
AB  - By substituting an ER3- unit (E = Group 13 element) or E'R3+ (E' = Group 15
      element) for CR3 one gets to methyl isosteres, compounds analogous to alkyls and
      isoelectronic or iso-valence-electronic to them. The substituent charge can be
      used to stabilize countercharged aromatic systems; some compounds of this type
      are known. Nature makes available all kinds of escape routes to such formally
      zwitterionic species. Strategies for impeding the often facile reaction channels
      that open up can be designed. We construct what we believe are viable further
      examples of zwitterionic methyl isosteres based on 3-, 5-, 7-, and 8-membered
      rings. A similar strategy is laid out for dicationic and dianionic xylene
      isosteres.

PMID- 30203651
TI  - CYP3A Activation and Glutathione Depletion Aggravate Emodin-Induced Liver Injury.
AB  - 1,3,8-Trihydroxy-6-methylanthraquinone (emodin), a widely existing natural
      product in herbal medicines, has been reported to be hepatotoxic, but the exact
      underlying mechanism is still not fully understood. The objective of the present
      study was to evaluate the role of CYP3A and glutathione (GSH) in emodin-induced
      liver injury. Primary human hepatocytes were exposed to emodin with and without
      addition of CYP3A inducer/inhibitor and GSH synthesis inhibitor. It was found
      that emodin-mediated cytotoxicity increased when CYP3A was activated and GSH was
      depleted. Hepatotoxicity induced by emodin in rats by activation/inhibition of
      CYP3A and depletion of GSH was further investigated. Administration of emodin in
      combination with l-buthionine sulfoximine (BSO) or dexamethasone (DEX) resulted
      in aggravated liver injury, whereas pretreatment with ketoconazole (KTZ)
      suppressed the side effects caused by emodin. In addition, plasma exposure of
      emodin and its glucuronide metabolite were measured by ultraperformance liquid
      chromatography triple quadrupole mass spectrometry. Emodin and its glucuronide
      were lower in BSO-, DEX-, and KTZ- co-treated rats compared with those
      administered with emodin alone. In conclusion, these mentioned results suggested
      that CYP3A induction and GSH depletion might be involved in hepatotoxicity
      induced by emodin. This study may help to understand the risk factors and the
      mechanism of hepatotoxicity of emodin in humans.

PMID- 30203652
TI  - Specific Gene Capture Combined with Restriction-Fragment Release for Directly
      Fluorescent Genotyping of Single-Nucleotide Polymorphisms in Diagnosing Spinal
      Muscular Atrophy.
AB  - In this study, a fast and simple fluorescent genotyping strategy, streptavidin
      magnetic beads combined with biotin-coupled PCR and restriction-fragment release,
      was developed for determination of nucleotide variants. This method was further
      applied for analyzing SMN1 gene in diagnosis of spinal muscular atrophy (SMA).
      After biotin-coupled PCR, the streptavidin magnetic beads would capture the
      biotin-labeled SMN genetic fragments, and then the restriction enzyme of HPY188I
      could only digest and release the fluorescent end of SMN1 genetic fragment into
      the supernatant. Therefore, the SMN1 gene could be easily fluorescently
      quantified, and SMN2 would not, for diagnosis of SMA. The copy number of the SMN1
      gene could be regressed using the relative fluorescent unit versus the known copy
      number, and the coefficient of correlation is equal to 0.9617 ( r = 0.9617). In
      this research, a total of 16 blind DNA samples were analyzed, including 6 wild
      types, 5 carriers, and 5 SMA patients. Importantly, this fast, simple, and highly
      efficient method is universal for detection of all nucleotides variants by
      replacing the specific restriction enzyme. This technique has the potency to be
      served as a tool for fast and accurate diagnosis of genotypes in clinical
      medicine.

PMID- 30203653
TI  - Copper(I)-Catalyzed Tandem One-Pot Synthesis of 2-Arylthiobenzothiazoles and 2
      Arylthiobenzoxazoles in Water.
AB  - An efficient tandem process for the preparation of 2-arylthiobenzothiazoles has
      been developed. By condensation of 2-aminobenzenethiol with tetramethylthiuram
      disulfide (TMTD), 2-mercaptobenzothiazoles was in situ generated, which
      susequently underwent coupling with iodobenzenes to give the desired 2
      arylthiobenzothiazoles fluently in a one-pot manner. This method can also be used
      for the synthesis of 2-arylthiobenzoxazoles. Inexpensive metal catalyst and
      ligand, mild reaction temperature, and water as solvent make this protocol
      practically valuable and useful in organic synthesis.

PMID- 30203654
TI  - Direct Link between Structure and Hydration in Ammonium and Aminium Bisulfate
      Clusters Implicated in Atmospheric New Particle Formation.
AB  - The acid-base chemistry of amines and sulfuric acid promotes growth in the early
      stages of atmospheric new particle formation, with more basic amines enhancing
      growth rates. Hydration of these particles has been proposed to depend on acidity
      or basicity but is difficult to quantify; therefore, the role of water in this
      process is not well understood. Using tandem mass spectrometry coupled to a
      temperature-controlled ion trap, we show that water uptake by aminium bisulfate
      clusters depends on the total number of free hydrogen bond donors in the cluster
      and is unaffected by the interchange of amines featuring the same number of
      substituents but differing gas-phase basicity. Analyzing this trend reveals site
      specific propensities for hydration. These results indicate that hydration is
      determined by structural factors and that reported dependences on acidity or
      basicity arise from the weaker correlation between the number of hydrogen bond
      donors of amines and their gas-phase basicity.

PMID- 30203655
TI  - Subcellular Proteome Landscape of Human Embryonic Stem Cells Revealed Missing
      Membrane Proteins.
AB  - Human embryonic stem cells (hESCs) have the capacity for self-renewal and
      multilineage differentiation, which are of clinical importance for regeneration
      medicine. Despite the significant progress of hESC study, the complete hESC
      proteome atlas, especially the surface protein composition, awaits delineation.
      According to the latest release of neXtProt database (January 17, 2018; 19 658
      PE1, 2, 3, and 4 human proteins), membrane proteins present the major category
      (1047; 48%) among all 2186 missing proteins (MPs). We conducted a deep
      subcellular proteomics analysis of hESCs to identify the nuclear, cytoplasmic,
      and membrane proteins in hESCs and to mine missing membrane proteins in the very
      early cell status. To our knowledge, our study achieved the largest data set with
      confident identification of 11 970 unique proteins (1% false discovery rate at
      peptide, protein, and PSM levels), including the most-comprehensive description
      of 6 138 annotated membrane proteins in hESCs. Following the HPP guideline, we
      identified 26 gold (neXtProt PE2, 3, and 4 MPs) and 87 silver (potential MP
      candidates with a single unique peptide detected) MPs, of which 69 were membrane
      proteins, and the expression of 21 gold MPs was further verified either by
      multiple reaction monitoring mass spectrometry or by matching synthetic peptides
      in the Peptide Atlas database. Functional analysis of the MPs revealed their
      potential roles in the pluripotency-related pathways and the lineage- and tissue
      specific differentiation processes. Our proteome map of hESCs may provide a rich
      resource not only for the identification of MPs in the human proteome but also
      for the investigation on self-renewal and differentiation of hESC. All mass
      spectrometry data were deposited in ProteomeXchange via jPOST with identifier
      PXD009840.

PMID- 30203656
TI  - Structural and Energetic Effects of O2'-Ribose Methylation of Protonated Purine
      Nucleosides.
AB  - The chemical difference between DNA and RNA nucleosides is their 2'-hydrogen
      versus 2'-hydroxyl substituents. Modification of the ribosyl moiety at the 2'
      position and 2'-O-methylation in particular, is common among natural post
      transcriptional modifications of RNA. 2'-Modification may alter the electronic
      properties and hydrogen-bonding characteristics of the nucleoside and thus may
      lead to enhanced stabilization or malfunction. The structures and relative
      glycosidic bond stabilities of the protonated forms of the 2'-O-methylated purine
      nucleosides, 2'-O-methyladenosine (Adom) and 2'-O-methylguanosine (Guom), were
      examined using two complementary tandem mass spectrometry approaches, infrared
      multiple photon dissociation action spectroscopy and energy-resolved collision
      induced dissociation. Theoretical calculations were also performed to predict the
      structures and relative stabilities of stable low-energy conformations of the
      protonated forms of the 2'-O-methylated purine nucleosides and their infrared
      spectra in the gas phase. Low-energy conformations highly parallel to those found
      for the protonated forms of the canonical DNA and RNA purine nucleosides are also
      found for the protonated 2'-O-methylated purine nucleosides. Importantly, the
      preferred site of protonation, nucleobase orientation, and sugar puckering are
      preserved among the DNA, RNA, and 2'-O-methylated variants of the protonated
      purine nucleosides. The 2'-substituent does however influence hydrogen-bond
      stabilization as the 2'-O-methyl and 2'-hydroxyl substituents enable a hydrogen
      bonding interaction between the 2'- and 3'-substituents, whereas a 2'-hydrogen
      atom does not. Further, 2'-O-methylation reduces the number of stable low-energy
      hydrogen-bonded conformations possible and importantly inverts the preferred
      polarity of this interaction versus that of the RNA analogues. Trends in the
      CID50% values extracted from survival yield analyses of the 2'-O-methylated and
      canonical DNA and RNA forms of the protonated purine nucleosides are employed to
      elucidate their relative glycosidic bond stabilities. The glycosidic bond
      stability of Adom is found to exceed that of its DNA and RNA analogues. The
      glycosidic bond stability of Guom is also found to exceed that of its DNA
      analogue; however, this modification weakens this bond relative to its RNA
      counterpart. The glycosidic bond stability of the protonated purine nucleosides
      appears to be correlated with the hydrogen-bond stabilization of the sugar
      moiety.

PMID- 30203657
TI  - Annulation of beta-Enaminonitriles with Alkynes via RhIII-Catalyzed C-H
      Activation: Direct Access to Highly Substituted 1-Naphthylamines and Naphtho[1,8-
      bc]pyridines.
AB  - A Cp*RhIII-catalyzed oxidative annulation of beta-enaminonitriles with alkynes
      was reported to achieve selective synthesis of polysubstituted 1-naphthylamines
      and naphtho[1,8- bc]pyridines via multiple C-H activations. Assisted by a
      naphthylamine NH2 group, 1-naphthylamines were also readily cyclized to produce
      naphtho[1,8- bc]pyridines. In addition, the obtained naphtho[1,8- bc]pyridine
      derivatives exhibit intense fluorescence in the solid state.

PMID- 30203658
TI  - Preliminary exploration of secondhand smoke exposure in youth with Sickle Cell
      Disease: biochemical verification, pulmonary functioning, and health care
      utilization.
AB  - Exposure to secondhand smoke (SHSe) can compound an already challenging set of
      health problems for youth with Sickle Cell Disease (SCD). Exposure to electronic
      cigarettes may also impact SCD symptomology and respiratory functioning. This
      study built on these previous findings by a) utilizing two objective measures of
      SHSe, salivary cotinine and exhaled carbon monoxide and b) examining the
      association of SHSe with emergency department utilization, physician-reported
      sickle cell crises, and pulmonary functioning. Caregivers (N = 31 dyads; Mage =
      37.6 years; SD = 8.5 years) of youth with SCD (Mage = 9.0 years; SD = 4.5 years)
      completed self-report measures of tobacco/nicotine use. Youth provided a saliva
      sample to assess cotinine levels, and performed pulmonary function tests. Dyads
      provided breath samples for measurement of eCO. A chart review was conducted to
      obtain medical history and utilization. Majority of youth (88%) were exposed to
      SHS via salivary cotinine. Interestingly, no significant associations were
      observed between youth cotinine levels and emergency department utilization,
      physician-reported sickle cell crises, or pulmonary functioning. Present findings
      indicate a need to assess for SHSe using objective assessment measures. Future
      research should investigate which specific factors contribute to increase
      SHSe/SHVe in youth with SCD.

PMID- 30203660
TI  - Pilot Study of a 3-Dimensional Method for Analysis of Pronation of the First
      Metatarsal of Hallux Valgus Patients.
AB  - BACKGROUND:: The current work sought to quantify pronation of the first
      metatarsal relative to the second metatarsal and of the proximal phalanx of the
      great toe relative to the first metatarsal. METHODS:: Three-dimensional models
      were reconstructed from weightbearing computed tomography (CT) images (10 hallux
      valgus, 10 normal). The orientations of bones related to hallux valgus (HV) (ie,
      the phalanx, first and second metatarsals) were determined from coordinate
      systems established by selecting landmarks. After determining the hallux valgus
      and intermetatarsal angles, additional calculations geometrically determined the
      3-dimensional (3D) angles using the aeronautical system of yaw-pitch-roll. The 3D
      geometrically determined angles were compared to the conventional plain
      radiographic angles. RESULTS:: HV measurements taken with CT and 3D computer
      aided design (3DCAD) geometric methods were the same as measurements taken from
      plain radiographs (P > .05). The average pronation of the first metatarsal
      relative to the second metatarsal was 8.2 degrees greater in the hallux valgus
      group (27.3 degrees) than in the normal group (19.1 degrees) (P = .044). A
      regression analysis of pronation vs intermetatarsal angle (IMA) was not found to
      be significant. There was also no correlation between pronation of the great toe
      and first metatarsal in the HV group. CONCLUSIONS:: The pronation angle of the
      first metatarsal relative to the second metatarsal between normal and hallux
      valgus patients was larger in HV patients but was not well correlated with the
      IMA. CLINICAL RELEVANCE:: The findings of this study indicate that pronation may
      need to be considered in the operative correction of hallux valgus for
      restoration of normal anatomy.

PMID- 30203659
TI  - Validation of simplified PESI score for identification of low-risk patients with
      pulmonary embolism: From the COMMAND VTE Registry.
AB  - BACKGROUND: The simplified pulmonary embolism severity index (sPESI) score has
      been reported to be useful in predicting 30-day mortality for patients with
      pulmonary embolism, which helps the identification of low-risk patients for early
      hospital discharge or home treatment. However, therapeutic decision-making should
      also be based on the risks of adverse events other than mortality. METHODS: The
      COMMAND VTE Registry is a multicentre registry enrolling consecutive patients
      with acute symptomatic venous thromboembolism in Japan between January 2010 and
      August 2014, and the current study population consisted of 1715 patients with
      pulmonary embolism. We calculated the sPESI score for each patient, and compared
      30-day rates of mortality, recurrent venous thromboembolism and major bleeding
      between sPESI scores of 0 and 1 or greater. RESULTS: Patients with a sPESI score
      of 0 accounted for 383 (22%) patients, and 110 (6.4%) patients died within 30
      days. The cumulative 30-day incidence of mortality was lower in patients with a
      sPESI score of 0 than those with a sPESI score of 1 or greater (0.5% vs. 8.1%,
      log rank P<0.001). There was no significant difference in the cumulative 30-day
      incidence of recurrent venous thromboembolism between patients with a sPESI score
      of 0 and 1 or greater (1.3% vs. 2.8%, log rank P=0.11). The cumulative 30-day
      incidence of major bleeding was lower in patients with a sPESI score of 0 than
      those with a sPESI score of 1 or greater (1.1% vs. 4.0%, log rank P=0.005).
      CONCLUSIONS: In patients with a sPESI score of 0, the 30-day mortality, recurrent
      venous thromboembolism and major bleeding rates were reasonably low. The sPESI
      score could be useful to identify candidates for early hospital discharge or home
      treatment.

PMID- 30203661
TI  - "Effect of Lithium and Valproate on Proliferation and Migration of Limbal
      Epithelial Stem/Progenitor Cells".
AB  - PURPOSE: The effects of lithium (Li) and Valproic Acid (VA) drugs have been
      recently revealed to improve the Mesenchymal stem cells')MSCs (migration and
      proliferation processes. The aim of this study is to determine the expression of
      the genes involved in the proliferation and migration of limbal epithelial
      stem/progenitor cells (LESPCs) after treatment with Li and VA. METHODS: After
      extraction of LSCs from human Corneoscleral tissue, cells were subcultured three
      times. The cell culture media were divided into four separate groups including
      groups treated with VA, Li, combination, and control groups after determining the
      non-toxic concentration of drugs (64mml) Li and (28mml) VA based on MTT assay,
      and then cells cultures were treated for 3 hours. A real-time polymerase chain
      reaction was performed to detect the expression levels of CD44, Ki67, CXCR4,
      CXCR7, MMP-2, MMP-9, and SDF-1 genes. Changes in the expression of each gene in
      different treatments were calculated. Finally, the graphs were analyzed by SPSS
      (Version 18) software. RESULTS: The highest expression of CXCR4 and CXCR7 was in
      the Li-treated group. Additionally, the highest expression levels of MMP-9 and
      CD44 genes were observed in the VA-treated group. In contrast, the expression
      level of SDF-1a, MMP2, and Ki67 genes in all three treatment groups reduced
      compared to the control group. CONCLUSION: Increasing the LSCs migration genes
      (CXCR4 and MMP9) was more evident than cell proliferation genes (Ki67). In sum,
      Li and VA can affect the process of proliferation and migration of LSCs in vitro.

PMID- 30203662
TI  - Quantitative In Situ Monitoring of Parahydrogen Fraction Using Raman
      Spectroscopy.
AB  - Raman spectroscopy has been used to provide a rapid, noninvasive, and
      nondestructive quantification method for determining the parahydrogen fraction of
      hydrogen gas. The basis of the method is the measurement of the ratio of the
      first two rotational bands of hydrogen at 355 cm-1 and 586 cm-1 corresponding to
      parahydrogen and orthohydrogen, respectively. The method has been used to
      determine the parahydrogen content during a production process and a reaction. In
      the first example, the performance of an in-house liquid nitrogen cooled
      parahydrogen generator was monitored both at-line and on-line. The Raman
      measurements showed that it took several hours for the generator to reach steady
      state and, hence, for maximum parahydrogen production (50%) to be reached. The
      results obtained using Raman spectroscopy were compared to those obtained by at
      line low-field nuclear magnetic resonance (NMR) spectroscopy. While the results
      were in good agreement, Raman analysis has several advantages over NMR for this
      application. The Raman method does not require a reference sample, as both spin
      isomers (ortho and para) of hydrogen can be directly detected, which simplifies
      the procedure and eliminates some sources of error. In the second example, the
      method was used to monitor the fast conversion of parahydrogen to orthohydrogen
      in situ. Here the ability to acquire Raman spectra every 30 s enabled a
      conversion process with a rate constant of [Formula: see text] s-1 to be
      monitored. The Raman method described here represents an improvement on
      previously reported work, in that it can be easily applied on-line and is
      approximately 500 times faster. This offers the potential of an industrially
      compatible method for determining parahydrogen content in applications that
      require the storage and usage of hydrogen.

PMID- 30203663
TI  - Conceptualizing Health Promotion in Relation to Outpatient Healthcare Building
      Design: A Scoping Review.
AB  - OBJECTIVE: This review explored different conceptualizations of health promotion
      in the context of, and in relation to, outpatient building design. BACKGROUND:
      Today's healthcare organizations are implementing holistic healthcare approaches
      such as health promotion, while simultaneously increasing their outpatient
      services. These health promotion approaches, focused on empowering people to take
      control of their health, are expected to have implications for the outpatient
      healthcare building design. Yet there is limited knowledge what these may be. A
      review of the literature on the current state of the art is thus needed to enable
      and support dialog on future healthcare building design. METHOD: A scoping review
      of 4,506 papers, collected from four databases and three scientific journals in
      2015, resulted in 14 papers relating health promotion to building design and
      outpatient healthcare. From the subsequent content analysis, multiple common
      themes and subthemes emerged. RESULTS: The review reveals diverse range of health
      promotion interpretations, three health promotion perspectives (health behavior,
      health equity, and sense of coherence), associated design approaches, design
      objectives, health-related outcomes, building features, and solutions.
      CONCLUSIONS: While diverse health promotion perspectives might merely represent
      variations in focus, these differences become problematic when relating to
      building design. To support further dialogs on development of health promotion
      in, and in relation to, the build environment, there is a need to strengthen the
      health promotion vocabulary. Further research is needed to compare different
      design approaches and how these can be combined to minimize contradicting
      implications for building design.

PMID- 30203664
TI  - Online social networking addiction and depression: The results from a large-scale
      prospective cohort study in Chinese adolescents.
AB  - BACKGROUND AND AIMS: The aim of this study is to estimate the longitudinal
      associations between online social networking addiction (OSNA) and depression,
      whether OSNA predicts development of depression, and reversely, whether
      depression predicts development of OSNA. METHODS: A total of 5,365 students from
      nine secondary schools in Guangzhou, Southern China were surveyed at baseline in
      March 2014, and followed up 9 months later. Level of OSNA and depression were
      measured using the validated OSNA scale and CES-D, respectively. Multilevel
      logistic regression models were applied to estimate the longitudinal associations
      between OSNA and depression. RESULTS: Adolescents who were depressed but free of
      OSNA at baseline had 1.48 times more likely to develop OSNA at follow-up compared
      with those non-depressed at baseline [adjusted OR (AOR): 1.48, 95% confidence
      interval (CI): 1.14-1.93]. In addition, compared with those who were not
      depressed during the follow-up period, adolescents who were persistently
      depressed or emerging depressed during the follow-up period had increased risk of
      developing OSNA at follow-up (AOR: 3.45, 95% CI: 2.51-4.75 for persistent
      depression; AOR: 4.47, 95% CI: 3.33-5.99 for emerging depression). Reversely,
      among those without depression at baseline, adolescents who were classified as
      persistent OSNA or emerging OSNA had higher risk of developing depression
      compared with those who were no OSNA (AOR: 1.65, 95% CI: 1.01-2.69 for persistent
      OSNA; AOR: 4.29; 95% CI: 3.17-5.81 for emerging OSNA). CONCLUSION: The findings
      indicate a bidirectional association between OSNA and depression, meaning that
      addictive online social networking use is accompanied by increased level of
      depressive symptoms.

PMID- 30203665
TI  - The Peer Review Process.

PMID- 30203666
TI  - Pharmacotherapy-Induced Hepatitis B Reactivation Among Patients With Prior
      Functional Cure: A Systematic Review.
AB  - OBJECTIVE: To describe and quantify the incidence and morbidity of hepatitis B
      reactivation (HBVr) secondary to pharmaceutical agents (eg, rituximab, tumor
      necrosis factor inhibitors, direct-acting antivirals [DAAs] for hepatitis C)
      among patients with previously resolved hepatitis B infection. DATA SOURCES: The
      MEDLINE database was searched from inception through July 2018 using the terms
      hepatitis B + ( reactivation OR [drug or drug class linked to HBVr]). STUDY
      SELECTION AND DATA EXTRACTION: Relevant English-language cohort studies or
      randomized trials quantifying the incidence of HBVr secondary to pharmacotherapy
      among patients negative for hepatitis B surface antigen and DNA and positive for
      hepatitis B core antibody were included. DATA SYNTHESIS: Among 2045 articles, 102
      met inclusion criteria. Receipt of rituximab was associated with the highest risk
      of HBVr (for oncological indication: 6.2% rate [225/3601 patients]) and
      subsequent hepatitis (up to 52.4% of all HBVr cases). Biologic agents for
      autoimmune disease were uncommonly associated with HBVr (2.4%, 56/2338), with
      only 4 cases of hepatitis, all attributable to rituximab. Reactivation caused by
      DAAs was rare (0.3%, 28/8398), with no cases of hepatitis. Relevance to Patient
      Care/Clinical Practice: This review compares and contrasts the incidence and
      clinical relevance of HBVr for various pharmacotherapies among patients with
      functionally cured hepatitis B, with discussion of appropriate risk mitigation
      strategies. CONCLUSIONS: Among patients with prior functional cure of hepatitis
      B, prophylactic antiviral therapy is recommended with rituximab administration
      irrespective of indication because of a high risk for HBVr-associated morbidity.
      Enhanced monitoring alone is reasonable for patients receiving nonrituximab
      biologics or DAAs.

PMID- 30203667
TI  - Clinical and Radiological Outcomes of Transfibular Total Ankle Arthroplasty.
AB  - BACKGROUND: Ankle arthritis is a highly limiting pathology that causes pain and
      functional limitation with subsequent deterioration of quality of life. With
      recent advances in surgical instrumentation and techniques, prosthetic
      replacement of the ankle has proven to be a valid alternative to arthrodesis with
      comparable outcomes. The purpose of this study was to evaluate clinical and
      radiological findings in a transfibular total ankle replacement with follow-up of
      at least 2 years. METHODS: This prospective study included 89 patients who
      underwent transfibular total ankle arthroplasty from May 2013 to February 2016.
      The mean age was 53.2 +/- 13.5 years. All patients were followed for at least 24
      months postoperatively with an average follow-up of 42.0 +/- 23.5 months.
      Patients were assessed clinically and radiographically preoperatively and at 6,
      12, and 24 months postoperatively. RESULTS: At 24 months postoperatively,
      patients demonstrated statistically significant improvement in the American
      Orthopaedic Foot & Ankle Society (AOFAS) Ankle Hindfoot Score from 33.8 +/- 14.3
      to 88.5 +/- 6.6 ( P < .001), visual analog scale (VAS) from 80.5 +/- 17.0 to 14.1
      +/- 9.2 ( P < .001), and Short Form-12 Physical and Mental Composite Scores from
      29.9 +/- 6.7 and 43.3 +/- 8.6 to 47.0 +/- 7.6 and 53.3 +/- 8.1, respectively ( P
      < .001). In addition, ankle dorsiflexion and plantarflexion improved from 6.2 +/-
      5.5 and 9.6 +/- 5.8 degrees to 24.2 +/- 7.9 and 18.1 +/- 7.6 degrees,
      respectively ( P < .001). Radiographically, patients demonstrated maintained
      neutral alignment of the ankle at 24 months. No patient demonstrated any
      radiographic evidence of tibial or talar lucency at final follow-up. Seven
      patients underwent reoperation for removal of symptomatic hardware (6 fibular
      plates, 1 syndesmotic screw); 2 patients experienced delayed wound healing. The
      first one was treated with plate removal and flap coverage. The second one
      required fibular plate removal. One patient developed a postoperative prosthetic
      infection requiring operative debridement, removal of implants, and placement of
      an antibiotic spacer. CONCLUSION: This study found that transfibular total ankle
      replacement was a safe and effective option for patients with ankle arthritis
      resulting in improvements in patient-reported outcomes, range of motion, and
      radiographic parameters. However, further studies are required to determine the
      mid- and long-term performance of these implants. LEVEL OF EVIDENCE: Level IV,
      case series.

PMID- 30203669
TI  - Synovial Fluid Fatty Acid Profiles Differ between Osteoarthritis and Healthy
      Patients.
AB  - Objective Free fatty acids (FAs) may influence cartilage metabolism and
      osteoarthritis (OA) disease progression. It is not clearly studied which FAs are
      present in the synovial fluid of knee joints and whether there are differences in
      FA content between nonsymptomatic and OA knee joints. The aim of this study was
      to investigate the presence of different types of FAs in synovial fluid of both
      OA- and nonsymptomatic control joints, and to analyze differences between both
      groups. Design A total of 23 synovial fluid samples were collected from patients
      with end-stage knee OA undergoing total knee replacement, with approval of the
      medical ethical committee. As controls, 6 synovial fluid samples were obtained
      from postmortem donors without any history of joint disease or arthritis.
      Measurement of free FA concentration was done by mass spectrometry for saturated
      FAs (SFA), monounsaturated FAs (MUFA), and omega-3 and omega-6 polyunsaturated
      FAs (n-3 PUFAs and n-6 PUFAs). Results Our measurements demonstrated the presence
      of SFAs, MUFAs, n-3 and n-6 PUFAs in synovial fluid of both nonsymptomatic and OA
      knee joints. The n-6/n-3 ratio was significantly lower in the OA group ( P =
      0.0005). Arachidonic acid (n-6 PUFA) concentrations were also lower in OA
      synovial fluid ( P = 0.01), while tetracosadienoic acid ( P = 0.0001) and
      nervonic acid ( P = 0.001) (MUFAs) were higher in synovial fluid of patients with
      knee OA. Conclusion Synovial fluid contains a broad spectrum of free FAs. The FAs
      profile differs between OA and control subjects, including a tendency for less n
      6 FAs in OA joints.

PMID- 30203668
TI  - Cost impact of the transitional care model for hospitalized cognitively impaired
      older adults.
AB  - AIM: The goal of this study was to compare postacute care costs of three care
      management interventions. MATERIALS & METHODS: A total of 202 hospitalized older
      adults with cognitive impairment received either Augmented Standard Care,
      Resource Nurse Care or the Transitional Care Model. The Lin method was used to
      estimate costs at 30 and 180 days postindex hospital discharge. RESULTS: The
      Transitional Care Model had significantly lower costs than the Augmented Standard
      Care group at both 30 (p < 0.001) and 180 days (p = 0.03) and significantly lower
      costs than Resource Nurse Care at 30 days (p = 0.02). CONCLUSION: These findings
      suggest that the Transitional Care Model can reduce both the amount of other
      postacute care and the total cost of care compared with alternative services for
      cognitively impaired older adults. Clinicaltrials.gov : NCT00294307.

PMID- 30203670
TI  - A rare complication of endoscopic sinus surgery: Retinal artery occlusion.
AB  - A 60-year-old patient with a history of diabetes mellitus and coronary artery
      disease was admitted to the eye nose and throat clinic due to complaints of
      difficulty in breathing. The patient was decided for functional endoscopic sinus
      surgery with the diagnosis of right nasal polyposis and chronic sinusitis. The
      patient had right visual loss with the findings of retinal artery occlusion,
      which is a rare ocular complication seen after functional endoscopic sinus
      surgery. Although the patient had proper urgent surgical and medical treatment,
      we did not observe visual improvement. Since this is a very rare condition, we
      intended to report it in the literature.

PMID- 30203671
TI  - Efficacy of addition of nepafenac 0.1% to steroid eye drops in prevention of post
      phaco macular edema in high-risk eyes.
AB  - PURPOSE: To compare the efficacy of addition of nonsteroidal anti-inflammatory
      eye drops to steroidal eye drops with that of using postoperative steroidal anti
      inflammatory eye drops alone in prevention of macular edema in high-risk
      patients. SETTING: Cairo University Hospital. DESIGN: This study was comparative
      prospective interventional randomized study. METHODS: This study included 100
      cataractous eyes divided into five subgroups: 20 eyes of diabetic patients, 20
      uveitic eyes, 20 traumatic cataracts, 20 glaucomatous eyes on topical
      prostaglandin analogs, and 20 eyes with posterior capsular rupture during
      phacoemulsification. Each subgroup of 20 was randomized between two groups of 10
      eyes, group A received postoperative topical steroids alone and group B received
      both steroidal and nonsteroidal anti-inflammatory eye drops. RESULTS: There was
      significant increase in postoperative central foveal thickness as compared to
      preoperative values in both groups (60.9 +/- 87.95 u in group A and 25.52 +/-
      57.26 u in group B) that was significantly more in group A (P value 0.016). There
      was significant difference in postoperative macular thickness between both groups
      (280.1 +/- 86.0 u and 246.80 +/- 57.73 u, respectively, in groups A and B) (P
      value = 0.012). There was no statistically significant difference between both
      groups in preoperative and postoperative corrected distance visual acuity and
      intraocular pressure. CONCLUSION: Addition of topical nepafenac eye drops to
      topical steroid drops significantly reduced the amount of pseudophakic macular
      edema after cataract surgery in high-risk eyes.

PMID- 30203672
TI  - Relationship between inflammatory parameters and cardiovascular and lifestyle
      factors in the Mugello study oldest old.
AB  - AIM: To explore possible inter-relationships of various biomarkers of
      inflammation and lifestyle and other cardiovascular risk factors (age, gender,
      smoking history, hypertension, Type 2 diabetes, dyslipidemia, alteration of
      circadian rhythms, body mass index, calf circumference, thigh circumference,
      abdominal circumference) in the Mugello study oldest old. METHODS: In 399
      noninstitutionalized nonagenarians (291 women), whole blood cells, mean platelet
      volume, C-reactive protein, uric acid, gamma-glutamyl transferase were assessed.
      RESULTS: Aging resulted as the only independent determinant for uric acid
      (<0.05), and abdominal circumference for C-reactive protein. Female gender
      (<0.01), and thigh circumference (<0.05) remained as determinants for mean
      platelet volume, age (<0.01), and male gender (<0.01) for gamma-glutamyl
      transferase, and Type 2 diabetes (<=0.01) and alteration of circadian rhythms
      (<0.05) for whole blood cells. CONCLUSION: Several inflammatory parameters remain
      associated with adverse lifestyle and cardiovascular risk factors even among
      nonagenarians.

PMID- 30203674
TI  - High Tech Solutions.

PMID- 30203673
TI  - Ameliorative effect of selenium nanoparticles and fish oil on cisplatin and gamma
      irradiation-induced nephrotoxicity in male albino rats.
AB  - Cisplatin (CP) is a major antineoplastic drug for the treatment of solid tumors,
      however, its clinical utility is limited by nephrotoxicity. Also, radiotherapy is
      an important treatment modality for many malignancies. The present studies were
      performed to test whether fish oil (FO) and/or selenium nanoparticles (SeNPs)
      administration have an ameliorative effect on CP and gamma-irradiation induced
      nephrotoxicity. FO and/or SeNPs were administered to male albino rats daily for
      12 days before being intraperitoneally injected with a single dose of CP (10
      mg/kg body weight) and whole body exposed to a single dose of gamma-radiation
      (0.7 Gy). Biochemical analysis and histopathological examination were performed.
      Pretreatment with FO and/or SeNPs before the administration of CP and exposure to
      gamma-radiation significantly reduced CP- and gamma-radiation-induced high levels
      of serum urea and creatinine and renal tumor necrosis factor-alpha, caspase-3 and
      cyclooxygenase-2, also they significantly prevented renal total antioxidant
      capacity levels decrease and ameliorated the levels of most studied trace
      elements. The histopathological results supported the biochemical findings of
      this study. The administration of FO and/or SeNPs might be useful for preventing
      nephrotoxicity which can be caused by CP and radiotherapy during the treatment of
      various malignancies.

PMID- 30203675
TI  - Analysis of Diethylstilbestrol Residues in Chicken Using Surface-Enhanced Raman
      Spectroscopy (SERS) Coupled with Multivariate Analysis.
AB  - Estrogen residues, including diethylstilbestrol in chicken, are one of the main
      food safety concerns all over the world owing to a series of negative effects on
      the human body. Surface-enhanced Raman spectroscopy (SERS) coupled with
      multivariate analysis was applied to detect rapidly diethylstilbestrol residues
      in chicken. The detection conditions, including the sizes of colloidal gold
      nanoparticles (Au NPs) and the additional amounts of Au NPs, chicken extract
      containing diethylstilbestrol, and magnesium sulfate solution, as well as the
      adsorption time, were optimized by a single factor experiment to obtain a better
      detection effect of diethylstilbestrol residues in chicken. Partial least squares
      regression (PLSR) was the best quantitative model for the detection of
      diethylstilbestrol residues in chicken by comparing four chemometric models.
      Diethylstilbestrol residues in chicken could be predicted by PLSR with the low
      root mean square error (RMSE = 0.4128 mg/L), and the high determination
      coefficient (R2 = 0.9811) and ratio of prediction to deviation (RPD = 7.2566) for
      the test set. A novel approach, which has the potential for the analysis of other
      estrogen residues in meat, was developed to detect rapidly the diethylstilbestrol
      residues in chicken by using SERS coupled with multivariate analysis.

PMID- 30203676
TI  - Presence of antigenotoxic and anticytotoxic effects of the chalcone 1E,4E-1-(4
      chlorophenyl)-5-(2,6,6-trimethylcyclohexen-1-yl)penta-1,4-dien-3-one using in
      vitro and in vivo assays.
AB  - Chalcones are chemically defined as alpha,beta-unsaturated ketones with a 1,3
      diphenyl-2-propen-1-one nucleus. These compounds occur naturally in plants and
      are considered precursors of flavonoids. Given that evaluating genetic toxicology
      tests is essential in investigating the safe use and chemopreventive potential of
      different natural and synthetic compounds, this study aimed to assess the
      genotoxic, cytotoxic, antigenotoxic, and anticytotoxic activity of the chalcone
      1E,4E-1-(4-chlorophenyl)-5-(2,6,6-trimethylcyclohexen-1-yl)penta-1,4-dien-3-one
      (CAB7beta). The CAB7beta was synthesized via Claisen-Schmidt reaction. The Ames
      test was applied using the co-treatment model as well as a micronucleus assay of
      mouse bone marrow with co-, pre- and post-treatment models. Our results indicate
      no genotoxic effect for CAB7beta in any of the tests applied. At all the
      concentrations used, CAB7beta showed a significant DNA protective effect against
      the mutagenic action of 4-nitroquinoline-1-oxide and sodium azide according to
      the Ames test, and against doxorubicin in the co-, pre- and post-treatment models
      of the micronucleus assay. CAB7beta alone displayed cytotoxic activity in the
      micronucleus test. At concentrations of 12,5 and 50 ug/plate, CAB7beta showed a
      moderate cytotoxic profile only in Salmonella typhimurium strain TA98. However,
      an anticytotoxic effect was observed against S. typhimurium strain TA100 for all
      the concentrations tested and during co-, pre- and post-treatment in the
      micronucleus assay. It was concluded that CAB7beta exhibited a slightly cytotoxic
      effect in S. typhimurium strain TA98 and significant antigenotoxic and
      anticytotoxic effects in cells of mouse, making it a promising candidate in
      chemoprevention and possibly in the development of new cancer treatments.

PMID- 30203677
TI  - Physical Activity Maintenance Following Home-Based, Individually Tailored Print
      Interventions for African American Women.
AB  - African American women report low participation in physical activity and are
      disproportionately burdened by related conditions (obesity, breast, and colon
      cancer). Physical activity interventions have shown promising results among
      African American women, but most studies in this area have focused on short-term
      increases. More enduring changes in health behavior will be needed to eliminate
      existing health disparities. Thus, the current study examined 12-month physical
      activity and psychosocial outcomes from a pilot randomized controlled trial ( N =
      84) of a Home-based Individually tailored Physical activity Print (HIPP)
      intervention for African American women in the Deep South. Retention was 77.4% at
      12 months. HIPP participants increased self-reported moderate-to-vigorous
      physical activity from 35.1 minutes/week (standard deviation [SD] = 47.8) at
      baseline to 124 minutes/week ( SD = 95.5) at 12 months, compared with the
      wellness contact control participants who reported increases from 48.2
      minutes/week ( SD = 51.3) to 102.5 minutes/week ( SD = 94.5) over 12 months
      (between-group p > .05). Results indicate that modest improvements in moderate-to
      vigorous physical activity and related psychosocial variables occurred during the
      active intervention phase (months 0-6) and were sustained during the tapered
      maintenance period (months 6-12). Low-cost, high-reach, home-based strategies
      have great potential for supporting sustained participation in physical activity
      and achieving long-term health benefits among African American women in the Deep
      South.

PMID- 30203678
TI  - Cross-sectional evaluation of the impact of information on flexible extended
      regimens of oral contraceptives in the choices made by women seeking
      contraceptive counselling: the FLEXO study.
AB  - OBJECTIVE: Oral combined hormonal contraceptives (CHCs) are available that limit
      the number of menses when used in a flexible extended regimen. Our aim was to
      investigate the decision-making processes of women presented with a flexible
      extended CHC option. METHODS: The FLEXO study is an epidemiological, cross
      sectional, multicentre study conducted under typical clinical practice conditions
      to determine women's acceptance of a flexible continuous CHC regimen versus a
      cyclical 21/7 day regimen, after receiving standardised information during
      contraceptive counselling. RESULTS: A total of 1350 women were invited to
      participate, of whom 1156 were enrolled. Of these, 47.2% chose the flexible
      extended CHC regimen. Their main reason for choosing this regimen was to reduce
      the number of menses (25.7%), followed by the desire to avoid symptoms related to
      menstruation (21.6%). The reasons given for rejecting this regimen were the
      desire to have monthly menstrual cycles (24.9%) and the fear of becoming pregnant
      and not being aware of it due to the absence of menstruation (18.1%). CONCLUSION:
      Many women chose the extended flexible regimen when they received information
      about this option. Women primarily chose this pattern to relieve or eliminate
      discomfort related to menstruation.

PMID- 30203679
TI  - Investigation of the effects of cephalosporin antibiotics on glutathione S
      transferase activity in different tissues of rats in vivo conditions in order to
      drug development research.
AB  - Glutathione S-transferases are multifunctional enzymes for the cellular defense
      against xenobiotics and provide protection for organism. In this study, the
      inhibition effects of some antibiotics were investigated against GST obtained
      from albino-rats kidney, liver, and heart tissues. Ninety-six albino-rats were
      randomly divided into 16 groups (n:6). The first four groups were control groups
      that were administrated blank enjection and decapitated at 1-7 h. The other
      groups were administrated the antibiotics. In all tissues, GST activity was
      increased in antibiotics groups at 1st and 3rd hours compared to control groups,
      while it began to fall at 5th and 7th hours (p < .05). In kidney tissues, it was
      lower than the same control group the cefuroxime and cefoperazone groups at 7th
      hours (p < .05). In addition, almost all antibiotic groups of kidney tissues had
      higher GST activity at all hours than those of control groups, but it was higher
      only at 5th hours in heart tissues (p < .05).

PMID- 30203680
TI  - Use of etonogestrel implant beyond approved duration: prolonged contraceptive
      effectiveness.
AB  - BACKGROUND: The subdermal etonogestrel contraceptive implant has a current
      approved duration of 3 years. There is, however, recent and strong evidence of
      its effectiveness for 2 additional years during which no pregnancies were
      documented. CASE: We report a case of a 28-year-old woman who had an etonogestrel
      implant inserted 4 years earlier and wished to get pregnant. The implant was,
      however, deep in the triceps muscle and could not easily be removed. Her serum
      levels of etonogestrel remained positive even 6 years after insertion. As
      infertility investigation revealed endometriosis and bilateral tubal obstruction
      she was referred for assisted reproduction. Despite obtaining oocytes during an
      ovarian stimulation cycle, the endometrium was never above 4 mm, precluding
      embryo transfer. It was decided to remove the implant in order to improve
      endometrial conditions, after which the patient achieved pregnancy. CONCLUSION:
      This case report suggests that the etonogestrel implant is effective for even
      longer than the most recent studies have shown.

PMID- 30203681
TI  - Phase II dose-finding study on ovulation inhibition and cycle control associated
      with the use of contraceptive vaginal rings containing 17beta-estradiol and the
      progestagens etonogestrel or nomegestrol acetate compared to NuvaRing.
AB  - PURPOSE: To identify at least one contraceptive vaginal ring that effectively
      inhibits ovulation and demonstrates cycle control that is non-inferior to
      NuvaRing(r) (Merck Sharp & Dohme B.V., The Netherlands) in terms of an
      unscheduled bleeding incidence, with a non-inferiority margin of 10%. METHODS:
      This was a randomised, active controlled, parallel group, multicentre, partially
      blinded trial in healthy women 18-35 years of age. Subjects received one of six
      contraceptive vaginal rings with an average daily release rate of 300 ug 17beta
      estradiol (E2) and various rates of either etonogestrel (ENG; 75, 100, or 125
      ug/day) or nomegestrol acetate (NOMAC; 500, 700, or 900 ug/day), or the active
      control NuvaRing(r) (ENG/ethinylestradiol 120/15 ug), for three 28-day cycles.
      RESULTS: Ovulation inhibition was observed in all groups as confirmed by absence
      of progesterone concentrations compatible with ovulation (>16 nmol/L) and absence
      of ultrasound evidence of ovulation. All investigational rings provided good
      cycle control, with the ENG-E2 125/300 ug/day group being associated with the
      best cycle control based on the numerically lowest incidence of unscheduled
      bleeding and absence of scheduled bleeding. Non-inferiority to NuvaRing(r) with
      respect to the incidence of unscheduled bleeding could not be concluded for any
      of the investigational ring groups. The safety profile was consistent with the
      known safety profile of combined estrogen/progestin contraceptives and similar
      across all groups. CONCLUSIONS: Contraceptive rings releasing 300 ug E2 and 75
      125 ug/day of ENG or 500-900 ug/day of NOMAC provided adequate ovulation
      inhibition and cycle control and are generally well-tolerated. While non
      inferiority to NuvaRing(r) was not met, among the investigational rings, the ENG
      E2 125/300 ring provided the best cycle control.

PMID- 30203682
TI  - Biphenyl-induced cytotoxicity is mediated by an increase in intracellular Zn2.
AB  - Biphenyl is found both in natural and anthropogenic sources and is used as a
      fungistat in the packaging of citrus fruits. Acute exposure to high levels of
      biphenyl has been observed to cause skin irritation and toxic effects on the
      liver and kidneys. However, the mechanisms of cytotoxicity induced by biphenyl
      are not yet well understood. In the present study, the cytotoxicity of biphenyl
      was studied by flow cytometry with fluorescent probes. Biphenyl at 100 MUM
      significantly increased cell lethality after 3 h in rat thymocytes. In addition,
      biphenyl at 100 MUM or more elevated intracellular Zn2+ levels. N,N,N',N'
      Tetrakis(2-pyridylmethyl)ethylenediamine (TPEN), an intracellular and
      extracellular Zn2+ chelator, but not diethylenetriamine-N,N,N',N",N"-pentaacetic
      acid (DTPA), a membrane-impermeable Zn2+ chelator, attenuated the biphenyl
      induced increase in intracellular Zn2+ levels and cell death. These results
      suggested that biphenyl-induced cytotoxicity caused an increase in intracellular
      Zn2+ levels, which was dependent on internal Zn2+. Moreover, biphenyl led to an
      increase in sensitivity to oxidative stress, while TPEN inhibited this biphenyl
      induced increase. Our findings revealed that biphenyl caused an increase in the
      intracellular free Zn2+ concentration, inducing cytotoxicity, cell death, and an
      increase in sensitivity to oxidative stress.

PMID- 30203683
TI  - Protective effects of glycyrrhizin on sub-chronic diazinon-induced biochemical,
      hematological alterations and oxidative stress indices in male Wistar rats.
AB  - The aim of this study was to elucidate the protective effect of glycyrrhizin on
      diazinon-induced changes in body and organ weights, blood hematology, lipid
      profile, biochemistry parameters and tissue markers of oxidative stress in male
      Wistar rats over a 7-week period. Rats were orally given sublethal dose of
      diazinon (10 mg/kg daily; 0.008 LD50), while glycyrrhizin (25 mg kg-1 daily) was
      given alone or in combination with diazinon. At the end of 7th week,
      statistically significant decrease of pseudocholinesterase activity was detected
      when diazinon- and glycyrrhizin + diazinon-treated groups were compared to the
      control group. Diazinon treated rats showed weight loss and organ weight changes
      which were comparable to other groups. There was a statistically significance in
      hematological indices except mean corpuscular hemoglobin (MCH) when diazinon
      treated group was compared to glycyrrhizin + diazinon treated rats. Glycyrrhizin
      protected the liver and kidney from diazinon toxic effects with significantly
      decrease in serum aspartate aminotransferase, alanine aminotransferase, alkaline
      phosphatase and lactate dehydrogenase activities as well as ameliorated hepatic
      and renal function indices (such as bilirubin, total protein, albumin, BUN,
      creatinine glucose). In addition, glycyrrhizin minimized the hazardous effect of
      diazinon on plasma lipids and lipoproteins. The protective effects of
      glycyrrhizin were confirmed by tissue markers of oxidative stress analysis as
      glycyrrhizin in combination diminished malondialdehyde and glycyrrhizin alone or
      in combination enhanced thiol group and the ferric reducing power. In accordance
      to these results, our observations demonstrated the beneficial effects of
      glycyrrhizin in reducing the toxicity of diazinon.

PMID- 30203684
TI  - Development of a Novel Pre-Vascularized Three-Dimensional Skin Substitute Using
      Blood Plasma Gel.
AB  - Skin substitutes with existing vascularization are in great demand for the repair
      of full-thickness skin defects. In the present study, we hypothesized that a pre
      vascularized skin substitute can potentially promote wound healing. Novel three
      dimensional (3D) skin substitutes were prepared by seeding a mixture of human
      endothelial progenitor cells (EPCs) and fibroblasts into a human plasma/calcium
      chloride formed gel scaffold, and seeding keratinocytes onto the surface of the
      plasma gel. The capacity of the EPCs to differentiate into a vascular-like
      tubular structure was evaluated using immunohistochemistry analysis and WST-8
      assay. Experimental studies in mouse full-thickness skin wound models showed that
      the pre-vascularized gel scaffold significantly accelerated wound healing 7 days
      after surgery, and resembled normal skin structures after 14 days post-surgery.
      Histological analysis revealed that pre-vascularized gel scaffolds were well
      integrated in the host skin, resulting in the vascularization of both the
      epidermis and dermis in the wound area. Moreover, mechanical strength analysis
      demonstrated that the healed wound following the implantation of the pre
      vascularized gel scaffolds exhibited good tensile strength. Taken together, this
      novel pre-vascularized human plasma gel scaffold has great potential in skin
      tissue engineering.

PMID- 30203685
TI  - Identification of Myocardial Telocytes and Bone Marrow Mesenchymal Stem Cells in
      Mice.
AB  - OBJECTIVES: The aim of this study was to compare the morphology, immune
      phenotype, and cytokine profiles between myocardial telocytes (TCs) and bone
      marrow mesenchymal stem cells (MSCs), and explore the difference between those
      two types of interstitial cells. METHODS: TCs and MSCs were cultured in vitro and
      cell morphology was observed with a light microscope. The expression levels of
      CD34, c-kit, and vimentin were detected by immunofluorescence, RT-qPCR, and
      Western blotting in both TCs and MSCs. The related supernatant was collected and
      total of 49 cytokine profiles were detected by RayBio Mice Cytokine Antibody
      Array. Significantly different cytokines were further confirmed by ELISA.
      RESULTS: TCs have small cellular body and very long prolongations and they were
      CD34+/c-kit+/vimentin+, whereas MSCs have no telopodes and they were CD34-/c-kit-
      /vimentin+. Cytokine profile analysis and ELISA showed that 19 of 49 cytokines
      were increased dramatically in the supernatant of TCs compared with those of
      MSCs. Moreover, 9 of 19 cytokines were increased 2-fold at least in the
      supernatant of TCs compared with those of MSCs. Of 49 cytokines, 30 exhibited no
      significant changes in the supernatant of TCs compared with those of MSCs.
      CONCLUSIONS: Using various technologies, we identified that myocardial TCs and
      MSCs are significantly different in terms of cell structure and cytokine
      profiles.

PMID- 30203686
TI  - Total Pancreatectomy and Islet Autotransplantation Following Treated Hepatitis C
      Infection.
AB  - Hepatic parenchymal disease, including chronic viral hepatitis, has traditionally
      been considered a relative contraindication to islet transplantation as the
      islets are infused into the recipient's liver. We present a case study of a
      patient with treated chronic hepatitis C infection (HCV) who safely received an
      autologous islet transplant following total pancreatectomy with excellent
      clinical outcomes. The patient was a 60-year-old woman diagnosed with
      debilitating abdominal pain secondary to chronic pancreatitis and with preserved
      islet function. She had previously been treated >10 years prior to surgical
      evaluation with interferon monotherapy for 1 year that led to sustained virologic
      response, including at the time of surgical evaluation for total pancreatectomy
      and islet autotransplantation (TPIAT). She underwent comprehensive preoperative
      evaluation of the liver, including liver biopsy, which showed no significant
      portal inflammation or fibrosis. Following a multidisciplinary meeting and
      discussion of the potential risks for the patient, the decision was made to
      proceed with TPIAT. The patient underwent a standard total pancreatectomy, and an
      autologous islet dose of 6638 islet equivalents/kg body weight was infused into
      the liver via the portal vein. Portal vein pressure was monitored throughout the
      infusion with a transient peak pressure of 27 cm H2O (basal pressure of 14 cm
      H2O) and final pressure of 23 cm H20 at 10 min post-infusion. Aside from a
      transient transaminitis, liver enzymes were normal at the time of hospital
      discharge. At greater than 1 year of follow-up, the patient has improved quality
      of life, with reduction in narcotic analgesia, remains insulin independent (with
      normal islet function), and has normal liver function. This case illustrates that
      islet autotransplant into the liver can be safely performed and suggests that
      carefully selected patients with liver disease may be eligible for TPIAT.

PMID- 30203689
TI  - Prevalence of enterotoxin-encoding genes among diverse Shigella strains isolated
      from patients with diarrhea, southwest Iran.
AB  - Shigella spp. are a major cause of bacillary dysentery, particularly among
      children in developing countries such as Iran. This study aimed to investigate
      the presence of two important Shigella enterotoxins (ShET-1 and ShET-2), encoded
      by the set and sen genes, respectively, by polymerase chain reaction (PCR) assay
      among Shigella species isolated from children affected by shigellosis in Ahvaz,
      southwest of Iran. In this cross-sectional study, from June 2016 to April 2017,
      altogether 117 Shigella isolates were collected from fecal specimens of children
      aged <15 years with diarrhea in Ahvaz, southwest Iran. All isolates were
      identified by standard microbiological and molecular methods. The presence of
      enterotoxin genes was determined by PCR. The most prevalent isolate was Shigella
      flexneri (47.9%), followed by Shigella sonnei (41%) and Shigella boydii (11.1%),
      respectively. Shigella dysenteriae was not detected in patients' samples. The
      frequencies of set1A, set1B, and sen genes were 5.1% (6/117), 15.4% (18/117), and
      76.9% (90/117), respectively. This study provides initial background on the
      prevalence and distribution of the Shigella enterotoxin genes in Shigella
      isolates in southwest of Iran. In addition, this study revealed a high prevalence
      of sen enterotoxin gene in Shigella species.

PMID- 30203687
TI  - Comparative Study on the Application of Mesenchymal Stromal Cells Combined with
      Tricalcium Phosphate Scaffold into Femoral Bone Defects.
AB  - This prospective study sought to evaluate the healing quality of implanted
      ultraporous beta-tricalcium phosphate sown with expanded autologous mesenchymal
      stromal cells (MSCs) into femoral defects during revision hip arthroplasty. A
      total of 37 osseous defects in 37 patients were treated and evaluated concerning
      bone regeneration. Nineteen subjects received beta-tricalcium phosphate graft
      material serving as a carrier of expanded autologous MSCs (the trial group A),
      nine subjects received beta-tricalcium phosphate graft material only (the study
      group B) and nine subjects received cancellous allografts only (the control group
      C). Clinical and radiographic evaluations were scheduled at 6 weeks, 3, 6, and 12
      months post-operatively, and performed at the most recent visit as well. All
      observed complications were recorded during follow-up to assess the use of an
      ultraporous beta-tricalcium phosphate synthetic graft material combined with
      expanded MSCs in bone defect repair. The resulting data from participants with
      accomplished follow-up were processed and statistically evaluated with a Freeman
      Halton modification of the Fischer's exact test, a P < 0.05 value was considered
      to be significant. Whereas no significant difference was observed between the
      trial group A with beta-tricalcium phosphate synthetic graft material serving as
      a carrier of expanded autologous MSCs and control group C with cancellous
      impaction allografting in terms of the bone defect healing, significant
      differences were documented between the study group B with beta-tricalcium
      phosphate graft material only and control group C. Regarding adverse effects, six
      serious events were recorded during the clinical trial with no causal
      relationship to the cell product. beta-tricalcium phosphate synthetic graft
      material serving as a carrier of expanded autologous MSCs appears safe and
      promotes the healing of bone defects in a jeopardized and/or impaired
      microenvironment. This clinical trial was registered at the EU Clinical Trials
      Register before patient recruitment (Registration number: EudraCT number 2012
      005599-33; Date of registration: 2013-02-04).

PMID- 30203688
TI  - Wharton's Jelly-Derived Mesenchymal Stem Cell Transplantation in a Patient with
      Hypoxic-Ischemic Encephalopathy: A Pilot Study.
AB  - Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) have been introduced as
      a possible therapy in hypoxic-ischemic encephalopathy (HIE). We report a 16-year
      old boy who was treated with WJ-MSCs in the course of HIE due to post
      cardiopulmonary resuscitation. He received a long period of mechanical
      ventilation and tracheostomy with spastic quadriparesis. He underwent the
      intrathecal (1*106/kg in 3 mL), intramuscular (1*106/kg in 20 mL) and intravenous
      (1*106/kg in 30 mL) administrations of WJ-MSCs for each application route (twice
      a month for 2 months). After stem cell infusions, progressive improvements were
      shown in his neurological examination, neuroradiological, and neurophysiological
      findings. To our best knowledge, this is a pioneer project to clinically study
      the neural repair effect of WJ-MSCs in a patient with HIE.

PMID- 30203691
TI  - Genotypic analysis of S segment of Crimean-Congo hemorrhagic fever virus in
      Turkey.
AB  - The Crimean-Congo hemorrhagic fever (CCHF) virus (CCHFV) is a tick-borne virus,
      whose viral RNA consists of S, L, and M segments. The virus is migrating through
      the ticks with animals and migratory birds and the geographical distribution can
      be investigated based on genetic analysis. To better understand the connection
      between the seropositivity and the mortality rate, the key factor could be the
      temporal and spatial analysis of the different strains. In this study, serum
      samples (n = 26) were selected from CCHFV RNA-positive patients and subjected to
      sequence analysis of the gene regions encoding the S segments. According to the
      neighbor-joining analysis, the obtained partial sequences were linked to the
      European strain. The strains were closely related to Turkey-Kelkit06, Turkey
      200310849 viruses, and viruses from Russia and Kosovo. The comparison with
      previously analyzed isolates from the GenBank showed 95%-99% sequence similarity.
      The isolates in phylogenetic branches were divided into two groups. AST,
      platelet, and APTT levels were found significantly higher in Group 2 compared to
      Group 1. Nucleotide differences can be prognostic factor in CCHF disease.
      Increasing CCHF cases not originating from local isolates were circulating
      strains imported from different neighboring countries of Turkey. The results show
      new evidence to the emerging threat of the CCHF disease.

PMID- 30203690
TI  - The relationship between structure and in vitro antistaphylococcal effect of
      plant-derived stilbenes.
AB  - Staphylococcus aureus is a major human pathogen that is responsible for both
      hospital- and community-acquired infections. Stilbenes are polyphenol compounds
      of plant origin known to possess a variety of pharmacological properties, such as
      antibacterial, antiviral, and antifungal effects. This study reports the in vitro
      growth-inhibitory potential of eight naturally occurring stilbenes against six
      standard strains and two clinical isolates of S. aureus, using a broth
      microdilution method, and expressing the results as minimum inhibitory
      concentrations (MICs). Pterostilbene (MICs = 32-128 MUg/ml), piceatannol (MICs =
      64-256 MUg/ml), and pinostilbene (MICs = 128 MUg/ml) are among the active
      compounds that possess the strongest activity against all microorganisms tested,
      followed by 3'-hydroxypterostilbene, isorhapontigenin, oxyresveratrol, and
      rhapontigenin with MICs 128-256 MUg/ml. Resveratrol (MIC = 256 MUg/ml) exhibited
      only weak inhibitory effect. Furthermore, structure-activity relationships were
      studied. Hydroxyl groups at ortho-position (B-3' and -4') played crucial roles
      for the inhibitory effect of hydroxystilbene piceatannol. Compounds with methoxy
      groups at ring A (3'-hydroxypterostilbene, pinostilbene, and pterostilbene)
      produced stronger effect against S. aureus than their analogues (isorhapontigenin
      and rhapontigenin) with methoxy groups at ring B. These findings provide
      arguments for further investigation of stilbenes as prospective leading
      structures for development of novel antistaphylococcal agents for topical
      treatment of skin infections.

PMID- 30203692
TI  - Tendencies toward Internet-pornography-use disorder: Differences in men and women
      regarding attentional biases to pornographic stimuli.
AB  - BACKGROUND AND AIMS: Several authors consider Internet-pornography-use disorder
      (IPD) as addictive disorder. One of the mechanisms that has been intensively
      studied in substance- and non-substance-use disorders is an enhanced attentional
      bias toward addiction-related cues. Attentional biases are described as cognitive
      processes of individual's perception affected by the addiction-related cues
      caused by the conditioned incentive salience of the cue itself. It is assumed in
      the I-PACE model that in individuals prone to develop IPD symptoms implicit
      cognitions as well as cue-reactivity and craving arise and increase within the
      addiction process. METHODS: To investigate the role of attentional biases in the
      development of IPD, we investigated a sample of 174 male and female participants.
      Attentional bias was measured with the Visual Probe Task, in which participants
      had to react on arrows appearing after pornographic or neutral pictures. In
      addition, participants had to indicate their sexual arousal induced by
      pornographic pictures. Furthermore, tendencies toward IPD were measured using the
      short-Internetsex Addiction Test. RESULTS: The results of this study showed a
      relationship between attentional bias and symptom severity of IPD partially
      mediated by indicators for cue-reactivity and craving. While men and women
      generally differ in reaction times due to pornographic pictures, a moderated
      regression analysis revealed that attentional biases occur independently of sex
      in the context of IPD symptoms. DISCUSSION: The results support theoretical
      assumptions of the I-PACE model regarding the incentive salience of addiction
      related cues and are consistent with studies addressing cue-reactivity and
      craving in substance-use disorders.

PMID- 30203693
TI  - Sleepiness and impulsivity: Findings in non-treatment seeking young adults.
AB  - BACKGROUND AND AIMS: Although inadequate sleep has been linked to problematic
      behaviors, such as poor impulse control and emotion dysregulation, little
      research interest has been the role of sleep and sleep deprivation on impulsive
      behaviors in young adults. To further examine the relationship of sleepiness to
      impulsivity and impulsive behaviors, this study was designed to collect data on
      sleepiness, and a range of impulse control disorders and cognitive measures.
      METHODS: Young non-treatment-seeking adults were recruited from two US cities and
      completed a screening form for sleepiness, along with demographic, clinical, and
      cognitive measures relevant to impulsivity. Relationships between these
      explanatory variables and total sleepiness scores were analyzed using partial
      least squares. Significant explanatory variables were identified (p < .05,
      bootstrap). RESULTS: Higher levels of sleepiness were significantly associated
      with higher ADHD symptoms, gambling disorder symptoms, Internet addiction
      symptoms, and personality-related impulsiveness. Sleepiness was also associated
      with set-shifting errors, and with gambling more points (abnormal decision
      making), but not with significant impairment in response to inhibition, or other
      aspects of decision-making. CONCLUSIONS: This study confirms a cross-sectional
      relationship between sleepiness and a range of impulsive measures at the level of
      behavior (ADHD, gambling, and Internet addiction) and personality traits.
      Longitudinal research would be required to explore causal mechanisms and the
      direction of any such effects. Screening for such mental health diagnoses in
      people with sleep problems may be valuable, as enquiring patients with such
      impulsive symptoms about sleep, in order to maximize quality of life.

PMID- 30203694
TI  - May the passion be with you: The addictive potential of collectible card games,
      miniatures, and dice of the Star Wars universe.
AB  - BACKGROUND AND AIMS: In recent years, we have witnessed a growing research
      interest in behavioral addictions and in pleasurable behaviors that generate a
      certain discomfort in the people who engage in them. The objective of this study
      was to assess if users of collectible card games, miniatures, and dice from the
      Star Wars Universe Games (SWUG) may also present criteria of addiction and if the
      presence of these criteria is related to demographic variables, game-playing
      habits, and other variables. METHODS: SWUG players were contacted through
      specialized gaming chats, and 218 of them completed the Internet Gaming Disorder
      Scale - Short Form (IGDS-SF9), a scale that assesses motivation to engage in the
      game (Massively Multiplayer Online Motivations Scale), the Rosenberg Self-Esteem
      Questionnaire, the Diener Satisfaction with Life Scale, and a question for the
      self-assessment of addiction. RESULTS: Significant predictors of addictive
      symptoms were the motivation to seek dissociation and (negatively) self-esteem.
      Users more significantly dedicate indirect hours to the game (thinking about the
      game, preparing material, etc.) than to actually playing. No participant could be
      considered pathologically addicted, as no one scored above the tentative cut-off
      point of the IGDS-SF9. DISCUSSION AND CONCLUSIONS: Despite the fact that many
      players considered themselves "addicted" and some presented various economic and
      family problems related to their activity, it was found that playing these games
      could not be equated to true addictive behavior, since no player had scores above
      the cut-off point. This finding contributes to current discussions about the
      tendency to overestimate excessive pleasurable behaviors.

PMID- 30203695
TI  - Does "forced abstinence" from gaming lead to pornography use? Insight from the
      April 2018 crash of Fortnite's servers.
AB  - In April 2018, the servers of the popular video game "Fortnite" crashed for 24
      hr. During this period, Pornhub (a popular pornographic website) analyzed trends
      in pornography access, finding that: (a) the percentage of gamers accessing
      Pornhub increased by 10% and (b) the searches of pornographic videos using the
      key term "Fortnite" increased by 60%. In this letter, we discuss these
      observations in the context of ongoing debate regarding the validity of
      "withdrawal" when applied to problematic involvement in video gaming and the
      potential use of pornography as a "compensation behavior" during the periods of
      "forced abstinence" from gaming.

PMID- 30203696
TI  - The relationship between sexual sensation seeking and problematic Internet
      pornography use: A moderated mediation model examining roles of online sexual
      activities and the third-person effect.
AB  - BACKGROUND AND AIMS: Internet pornography consumption is prevalent among college
      students and problematic for some, yet little is known regarding the
      psychological constructs underlying problematic Internet pornography use (PIPU).
      Drawing on the Interaction of Person-Affect-Cognition-Execution model, this study
      tested a model that sexual sensation seeking (SSS) would impact PIPU through
      online sexual activities (OSAs) and that this relationship would be influenced by
      the third-person effect (TPE; a social cognitive bias relating to perceived
      impacts on others as compared to oneself) in a gender-sensitive manner. METHODS:
      A total of 808 Chinese college students (age range: 17-22 years, 57.7% male) were
      recruited and surveyed. RESULTS: Men scored higher than women on OSAs and PIPU
      and on each scale's component factors. The relationship between SSS and PIPU was
      mediated by OSAs, and the TPE moderated this relationship: the predictive path
      (SSS to PIPU) was significant only in participants with high TPE. The moderated
      mediation model was not invariant across gender groups, with data suggesting that
      it accounted for a greater proportion of the variance in men as compared with
      women. DISCUSSION AND CONCLUSIONS: The findings suggest that SSS may operate
      through participation in OSAs to lead to PIPU, and this relationship is
      particularly relevant for college-aged males scoring high on the TPE. These
      findings have implications for individuals who might be particularly vulnerable
      to developing PIPU and for guiding educational efforts and targeting
      interventions in college-aged students. The extent to which these findings extend
      to other age groups and cultures warrants further examination.

PMID- 30203697
TI  - Chemiluminescence imaging of UVA induced reactive oxygen species in mouse skin
      using L-012 as a probe.
AB  - Reactive oxygen species (ROS) caused by ultraviolet A (UVA) can be reduced by
      treating with antioxidants and photoprotective reagents. Here we reported a real
      time chemiluminescence (CL) imaging method which was simple, non-invasive and
      sensitive to evaluate UVA-induced ROS generation and the efficacy of sunscreens
      and antioxidants in vivo. The in vitro experiments indicated that l-ascorbic
      acid, live SPSC01 yeast, and its intracellular metabolites can suppress the
      intensity of CL signals in the presence of hydrogen peroxide, which proved the
      good antioxidant ability of them. Meanwhile, we used 8-amino-5-chloro-7
      phenylpyrido[3,4-d] pyridazine-1,4(2H,3H) dione (L-012) as a high sensitive CL
      probe for in vivo imaging of ROS generated by UVA irradiation. The CL intensity
      was reduced after treated with l-ascorbic acid and SPSC01 yeast intracellular
      metabolites, consistent with the in vitro results. Additionally, the in vivo
      protective capability of two azobenzene compounds as sunscreens was confirmed
      further through the suppression of CL signals of UVA-induced ROS in mouse skin by
      this method.

PMID- 30203698
TI  - Nonlinear analysis of heart rate variability of healthy subjects and patients
      with chronic obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD) is one of the causes of mortality
      worldwide with an increasing prevalence. Heart rate variability (HRV) reflects
      the regulation mechanism of the cardiac activity by the autonomic nervous system.
      The assessment of HRV by using nonlinear methods is more sensitive for the
      detection of complexity when compared to linear methods. This study aims to get
      information about the autonomic dysfunction occurred in patients with COPD by
      analysing the complexity of HRV. Electrocardiogram signals recorded from healthy
      subjects, patients with moderate COPD and severe COPD (eight subjects per group)
      were analysed. The HRV signals were acquired from ECG signals. Signals were
      reconstructed in the phase space and largest Lyapunov exponent (LLE), correlation
      dimension, Hurst exponent and approximate entropy (ApEn) values were calculated.
      It has seen that for the patients with COPD LLE, correlation dimension, Hurst
      exponent and ApEn values were less than control group. According to this, HRV
      complexity decreases in the presence of COPD. However, there is no significant
      difference between COPD groups and the severity of COPD has no effect on the
      chaoticity of the system. The results revealed that autonomic dysfunction
      occurred in patients with COPD is associated with reduced HRV complexity.

PMID- 30203699
TI  - Urinary Incontinence Is Associated With Physical Performance Decline in Community
      Dwelling Older Women: Results From the International Mobility in Aging Study.
AB  - OBJECTIVE: The objective of this study is to evaluate the influence of urinary
      incontinence (UI) on physical performance. METHOD: In prospective analyses from
      the International Mobility in Aging Study (IMIAS), 915 women (65-74 years) from
      Canada, Colombia, Albania, and Brazil were evaluated in relation to self-reported
      UI (past week) and physical performance (Short Physical Performance Battery
      [SPPB]), with reevaluation after 2 years. Linear mixed models examined the
      influence of UI on SPPB, adjusted by covariates (age, study site, education,
      income sufficiency, body mass index [BMI] and parity). RESULTS: Women reporting
      some UI presented lower SPPB mean (beta = -0.41, p = .009) and a greater
      reduction (beta = -0.53, p = .001) over 2 years than those reporting no UI.
      DISCUSSION: Compared with no reported UI, some UI was associated with worse and
      more pronounced declines in physical performance over 2 years. This study
      highlights the importance of practices to reduce UI to contribute to healthier
      aging.

PMID- 30203701
TI  - Impact of Prolonged Inflation Times During Plain Balloon Angioplasty on
      Angiographic Dissection in Femoropopliteal Lesions.
AB  - PURPOSE: To investigate if balloon angioplasty with a prolonged inflation time
      (>3 minutes) can prevent postdilation dissection in femoropopliteal lesions.
      METHODS: A retrospective single-center analysis examined 294 consecutive patients
      (mean age 74.1+/-8.7 years; 215 men) with de novo femoropopliteal lesions treated
      with balloon angioplasty between 2013 and 2018. The patients were classified into
      2 groups to compare angiographic dissection patterns: 175 patients treated with
      balloon angioplasty for 3 minutes (3-minute group) and 119 treated for >3 minutes
      (>3-minute group). RESULTS: Mean balloon inflation time was 7.8+/-2.7 minutes in
      the >3-minute group. Severe dissections (type C or higher) were observed less
      frequently after balloon dilation in the >3-minute group (22.7% vs 50.9%,
      p<0.001); therefore, significantly more patients in the >3-minute group had
      successful endovascular treatment after initial balloon angioplasty (57.1% vs
      38.3%, p=0.001). Additional balloon dilation was attempted more frequently in the
      3-minute group (30.9% vs 14.3%, p=0.001); as a result, there were more patients
      in whom additional balloon dilation repaired severe dissection that occurred
      after the initial dilation (25.1% vs 10.9%, p=0.001). Multivariate analysis
      revealed that chronic total occlusion (p<0.001) and longer lesion (p<0.001) were
      independent predictors of severe dissection, and prolonged dilation time was
      independently related to preventing severe dissection (p<0.001). Among 171
      patients undergoing successful balloon angioplasty without stent implantation,
      the Kaplan-Meier estimates of primary patency within 1 year did not differ
      significantly according to inflation time. CONCLUSION: Balloon dilation with
      prolonged inflation time (>3 minutes) may be effective as an initial strategy to
      prevent severe dissection in femoropopliteal lesions compared to inflation for 3
      minutes.

PMID- 30203702
TI  - Involvement of telomerase activity inhibition and telomere dysfunction in silver
      nanoparticles anticancer effects.
AB  - AIM: To investigate the possible mechanisms of telomerase and telomere underlying
      the anticancer effects of silver nanoparticles (AgNPs). MATERIALS & METHODS: 25nm
      polyvinylpyrrolidone-coated AgNPs were used. The telomerase activity and telomere
      function were evaluated. The anticancer effects of AgNPs were gauged with cell
      viability assay under different statement of telomerase and telomere. RESULTS &
      CONCLUSION: AgNPs could inhibit telomerase activity and lead to telomere
      shortening and dysfunction. Overexpression of telomerase attenuated the
      anticancer activity of AgNPs, whereas downregulation of telomerase activity or
      dysfunction of the telomere enhanced the cytotoxicity of AgNPs in HeLa cells. Our
      findings provided strong evidence that the anticancer effects of AgNPs were
      mediated via interference with the telomerase/telomere.

PMID- 30203703
TI  - TGF-beta1 induces epithelial-to-mesenchymal transition via inhibiting
      mitochondrial functions in A549 cells.
AB  - Epithelial-to-mesenchymal transition (EMT) is critical to the progression of
      several disease processes including carcinoma metastasis and organ fibrosis.
      Recent studies show that reactive oxygen species (ROS) and mitochondrial
      dysfunction have been associated with EMT. However, the role of mitochondria in
      the EMT process remains to be elucidated. Through the induction of EMT using TGF
      beta1, we demonstrated that mitochondrial functions were abnormal by increasing
      ROS production and reducing mitochondrial membrane potential, ATP content and
      mitochondrial complex protein expression. Resveratrol, a mitochondria protective
      agent, was found to prevent EMT by preserving mitochondrial functions during the
      process. However, the inhibitory effects of resveratrol on EMT were abolished in
      mitochondrial DNA-depleted cells. These findings suggest a critical role for
      mitochondria in EMT and implicate the protection of mitochondria as a potential
      target to prevent EMT to treat tumour metastasis or tissue fibrosis, and other
      diseases involving with mitochondria.

PMID- 30203704
TI  - Closely Related Fruit Fly Species Living at Different Latitudes Diverge in Their
      Circadian Clock Anatomy and Rhythmic Behavior.
AB  - Recently, we reported differences in the expression pattern of the blue light
      sensitive flavoprotein cryptochrome (CRY) and the neuropeptide pigment-dispersing
      factor (PDF) in the neuronal clock network of high-latitude Drosophila species,
      belonging to the Drosophila subgenus ( virilis-repleta radiation), compared with
      cosmopolitan D. melanogaster flies, belonging to the Sophophora subgenus.
      Alterations in rhythmic patterns of activity due to these differences might have
      adaptive significance for colonizing high-latitude habitats and, hence, adjusting
      to long photoperiods. Here, we show that these differing CRY/PDF expression
      patterns are only present in those species of the virilis-repleta radiation that
      colonized high latitudes. The cosmopolitan species D. mercatorum and D. hydei
      have a D. melanogaster-like clock network and behavior despite belonging to the
      virilis-repleta radiation. Similarly, 2 species of the holotropical Zaprionus
      genus, more closely related to the Drosophila subgenus than to the Sophophora
      subgenus, retain a D. melanogaster-like clock network and rhythmic behavior. We
      therefore suggest that the D. melanogaster-like clock network is the "ancestral
      fly clock phenotype" and that alterations in the CRY/PDF clock neurochemistry
      have allowed some species of the virilis-repleta radiation to colonize high
      latitude environments.

PMID- 30203705
TI  - Variability of functional outcome measures used in animal models of stroke and
      vascular cognitive impairment - a review of contemporary studies.
AB  - Despite promising preclinical data, few novel stroke therapies have shown
      efficacy in man. Efforts to improve standards in conduct and reporting of
      preclinical research are ongoing. In clinical trials, inconsistency in outcome
      measures led to regulatory agencies and funders mandating use of a core set of
      functional outcomes. Our aim was to describe functional outcome measures in
      preclinical stroke and vascular cognitive impairment (VCI) studies. From 14 high
      impact journals (January 2005-December 2015 inclusive), 91,956 papers were
      screened with 1302 full texts analyzed for stroke (ischemic and hemorrhagic) and
      56 for VCI studies. In total, 636 (49%) stroke and 37 (66%) VCI papers reported
      functional outcome measures. There were 74 different functional assessments
      reported in stroke and 20 in VCI studies. Neurological deficit scores (74%) and
      Morris water maze (60%) were most commonly used in stroke and VCI, respectively.
      However, inconsistencies in methods used to assess and score recovery were noted.
      Neurological and behavioural functional outcome measures are increasingly used in
      preclinical stroke or VCI studies; however, there is substantial variation in
      methods. A strict standardized outcome set may not be suitable for translational
      work, but greater consistency in choice, application and reporting of outcomes
      may improve the science.

PMID- 30203707
TI  - A review and empirical comparison of causal inference methods for clustered
      observational data with application to the evaluation of the effectiveness of
      medical devices.
AB  - Observational studies are commonplace in medicine. A frequent concern is
      confounding bias due to differences in patient characteristics across treatment
      groups, but other important issues include dependency among observations nested
      within clusters (e.g. patients clustered within physicians or surgeons) and
      confounding due to cluster characteristics (e.g. physician or surgeon experience
      or training). Given the frequency with which these issues arise in medical
      research, as well as their relative complexity, methods for the analysis of
      clustered observational data are reviewed. We argue for estimating causal
      treatment effects using marginal models that either match or weight observations
      using a suitable distance metric (e.g. the propensity score). Simulation results
      demonstrated that methods incorporating clustering into calculation of the
      variance were generally more accurate than those that did not. Moreover, methods
      that account for cluster confounding when estimating the treatment effect were
      least biased and most accurate. Throughout the paper we illustrate the proposed
      methods in a medical device setting that compares the effectiveness of femoral
      heads used in total hip replacements. Whenever possible the clustered aspect of
      the data should be considered in the design of the study when constructing the
      distance measure or in the matching process, as well as in the analysis when
      estimating the variance of the treatment effect.

PMID- 30203708
TI  - Commentary: Getting Back to Basics: Optimization of Plain Balloon Angioplasty.

PMID- 30203706
TI  - Global Trends and Prostate Cancer: A Review of Incidence, Detection, and
      Mortality as Influenced by Race, Ethnicity, and Geographic Location.
AB  - Although research has reported that prostate cancer (PCa) incidence and mortality
      rates are among the highest for African Americans, the data is inconclusive
      regarding PCa rates in native African men, Black men residing in other countries,
      and men in Asia, Europe, and the Americas. Data reveals that prostate-specific
      antigen (PSA) testing and disease incidence have risen significantly in
      developing and Asian countries, and PCa has become one of the leading male
      cancers in many of those nations. The objective of this study was to review
      published peer-reviewed studies that address PCa in different regions of the
      world to get a better understanding of how PCa incidence, prevalence, detection,
      and mortality are influenced by race, ethnicity, and geography. A secondary goal
      was to compare PCa data from various world regions to contextualize how
      disproportionate the incidence and mortality rates are among men from the African
      diaspora versus men of European, Hispanic, and Asian descent, as well as to
      highlight the need for more robust screening and treatment guidelines in
      developing countries. There are differences in incidence and mortality rates
      between men of African, Asian, Hispanic, and European ancestry, confirming the
      involvement of genetic factors. However, differences between men of the same race
      and ethnicity who live in different countries suggest that environmental factors
      may also be implicated. Availability and access to diagnostic and health-care
      services as well as recommendations regarding PCa testing vary from country to
      country and contribute to the variability in incidence and mortality rates.

PMID- 30203709
TI  - Stilbenoid pterostilbene complexed with cyclodextrin preserves left ventricular
      function after myocardial infarction in rats: possible involvement of thiol
      proteins and modulation of phosphorylated GSK-3beta.
AB  - Oxidative stress alters signalling pathways for survival and cell death favouring
      the adverse remodelling of postmyocardial remnant cardiomyocytes, promoting
      functional impairment. The administration of pterostilbene (PTS), a phytophenol
      with antioxidant potential, can promote cardioprotection and represents a
      therapeutic alternative in acute myocardial infarction (AMI). The present study
      aims to explore the effects of oral administration of PTS complexed with
      hydroxypropyl-beta-cyclodextrin HPbetaCD (PTS:HPbetaCD complex) on the
      glutathione cycle, thiol protein activities and signalling pathways involving the
      protein kinase B (AKT) and glycogen synthase kinase-3beta (GSK-3beta) proteins in
      the left ventricle (LV) of infarcted rats. Animals were submitted to acute
      myocardial infarction through surgical ligation of the descending anterior branch
      of the left coronary artery and received over 8 days, by gavage, PTS:HPbetaCD
      complex at dose of 100 mg kg-1 day-1 (AMI + PTS group) or vehicle (aqueous
      solution with HPbetaCD) divided into Sham-operated (SHAM) and infarcted (AMI)
      groups. The results showed that the PBS: HPbetaCD complex decreased lipid
      peroxidation, prevented the decrease in thioredoxin reductase (TRxR) activity,
      and increased the activity of glutathione-S-transferase (GST) and glutaredoxin
      (GRx). Additionally, the expression of nuclear factor-erythroid two (Nrf2) and p
      GSK-3beta was increased, whereas the p-GSK-3beta/GSK-3beta ratio was reduced in
      the LV of the infarcted animals. Overall, the PTS:HPbetaCD complex modulates
      activity of thiol-dependent enzymes and induces to the expression of antioxidant
      proteins, improving systolic function and mitigating the adverse cardiac
      remodelling post infarction.

PMID- 30203711
TI  - Cellular Therapy in Rare Childhood Neurologic Disease: Lessons, Outcomes, and
      Access.

PMID- 30203710
TI  - The Molecular Imaging of Natural Killer Cells.
AB  - The recent success of autologous T cell-based therapies in hematological
      malignancies has spurred interest in applying similar immunotherapy strategies to
      the treatment of solid tumors. Identified nearly 4 decades ago, natural killer
      (NK) cells represent an arguably better cell type for immunotherapy development.
      Natural killer cells are cytotoxic lymphocytes that mediate the direct killing of
      transformed cells with reduced or absent major histocompatibility complex (MHC)
      and are the effector cells in antibody-dependent cell-mediated cytotoxicity.
      Unlike T cells, they do not require human leukocyte antigen (HLA) matching
      allowing for the adoptive transfer of allogeneic NK cells in the clinic. The
      development of NK cell-based therapies for solid tumors is complicated by the
      presence of an immunosuppressive tumor microenvironment that can potentially
      disarm NK cells rendering them inactive. The molecular imaging of NK cells in
      vivo will be crucial for the development of new therapies allowing for the
      immediate assessment of therapeutic response and off-target effects. A number of
      groups have investigated methods for detecting NK cells by optical, nuclear, and
      magnetic resonance imaging. In this review, we will provide an overview of the
      advances made in imaging NK cells in both preclinical and clinical studies.

PMID- 30203714
TI  - Spleen tyrosine kinase-dependent Nrf2 activation regulates oxidative stress
      induced cell death in WiL2-NS human B lymphoblasts.
AB  - Autoimmune rheumatic lesions are often characterised by the immune cell
      recruitment including B lymphocytes and the presence of reactive oxygen species
      (ROS), which increase antioxidant gene transcription via nuclear factor
      (erythroid-derived 2)-like 2 (Nrf2). Spleen tyrosine kinase (Syk) has a major
      role in the signal transmission of all haematopoietic lineage cells including B/T
      cells, mast cells, and macrophages. In this study, we investigated whether B cell
      survival is regulated by Nrf2 via ROS-mediated Syk activation in WiL2-NS human B
      lymphoblast cells. When WiL2-NS cells were incubated with 1% foetal bovine serum
      (FBS), the survival rate and mitochondrial membrane potential (MMP) were reduced.
      In addition, 1% FBS increased caspase 3 activity, cytochrome C release, nuclear
      localisation of Nrf2, and ROS production. N-acetylcysteine attenuated ROS
      production and nuclear translocation of Nrf2. It also inhibited cell death,
      caspase 3 activation, MMP collapse, and cytochrome C release. Results from the 1%
      FBS treatment were consistent with those of H2O2 treatment. Syk phosphorylation
      at tyrosine 525/526 was increased by incubation with 1% FBS or treatment with 100
      uM H2O2. Nuclear translocation of Nrf2 by H2O2 was inhibited by treatment with
      BAY61-3606, a Syk inhibitor. BAY61-3606 also promoted MMP collapse, cytochrome C
      release, caspase 3 activation, and cell death. Taken together, these results
      implicate that Syk controls oxidative stress-induced human B cell death via
      nuclear translocation of Nrf2 and MMP collapse. These results suggest that Syk is
      a novel regulator of Nrf2 activation.

PMID- 30203715
TI  - Correction.

PMID- 30203716
TI  - Using genomics to guide treatment for glioblastoma.
AB  - Glioblastoma has been shown to have many different genetic mutations found both
      within and between tumor samples. Molecular testing and genomic sequencing has
      helped to classify diagnoses and clarify difficult to interpret histopathological
      specimens. Genomic information also plays a critical role in prognostication for
      patients, with IDH mutations and MGMT methylation having significant impact of
      the response to chemotherapy and overall survival of patients. Unfortunately,
      personalized medicine and targeted therapy against specific mutations have not
      been shown to improve patient outcomes. As technology continues to improve, exome
      and RNA sequencing will play a role in the design of clinical trials,
      classification of patient subgroups and identification of rare mutations that can
      be targeted by small-molecule inhibitors and biologic agents.

PMID- 30203718
TI  - How to treat hepatic pulmonary fusion: case report with review of literature.
AB  - INTRODUCTION: Hepatic pulmonary fusion (HPF) occurring with right diaphragmatic
      hernia is rare. Some sporadic reports exist in the literature. It may range from
      just fibrovascular communication to complete parenchymal fusion which may be
      complex to divide. PATIENTS AND METHODS: We report a case of a 1-day old newborn
      male presented with respiratory distress relevant to a right diaphragmatic
      hernia. RESULTS: The patient was operated after initial stabilization. During
      surgery, a 10-cm wide posterolateral defect was found. The herniated liver was
      only partially reducible because of HPF. This rare condition was treated by the
      division of the fusion and diaphragm repair using a vicryl patch. CONCLUSION:
      Through our case and a review of the literature, we will discuss the different
      alternatives in the treatment of HPF.

PMID- 30203717
TI  - Pancreaticoduodenectomy for periampullary cancer: does the tumour entity
      influence perioperative morbidity and long-term outcome?
AB  - BACKGROUND: Malignant tumours of the periampullary region include ductal
      adenocarcinoma of the pancreas (Pan-Ca), distal bile duct cancer (DBDC) and
      adenocarcinoma of the ampulla (Amp-Ca). The present retrospective clinical study
      was designed to evaluate the influence of tumour entity on postoperative
      complications and identify risk factors predicting survival and morbidity.
      METHODS: We retrospectively analysed data from all patients who underwent
      pancreatic resection for periampullary cancer with curative intent (R0 or R1).
      Demographic data, risk factors, perioperative complications and survival rates
      for the different subtypes were assessed. RESULTS: A total of 225 patients with
      periampullary cancer were identified: 124 (55.1%) had Pan-Ca, 55 (24.4%) had DBDC
      and 46 had (20.4%) Amp-Ca. Sixty-nine patients (30.7%) had major complications
      (grade IIIb-V). Patients with DBDC had significantly more grade C pancreatic
      fistulas. Univariate analysis revealed male gender, BMI >30, R1-status, and low
      grade tumour differentiation as risk factors for major complications. Overall in
      hospital-mortality was 6.7%. CONCLUSIONS: Further research will be needed to
      implement more individualized therapy.

PMID- 30203719
TI  - High-risk screening and detection of multidrug-resistant tuberculosis in two
      prefectures of China: a drug susceptibility surveillance-based secondary data
      analysis.
AB  - BACKGROUND: In China, less than one-fifth of multidrug-resistant tuberculosis
      (MDR-TB) cases are detected. MDR-TB screening is conducted amongst the following
      five high-risk groups of TB patients: chronic cases, close contacts of MDR-TB
      patients, patients with treatment failure, relapsed and returned patients, and
      smear-positive patients at the end of the third month of initial treatment.
      OBJECTIVE: To estimate the possibility of detecting MDR-TB cases if only the high
      risk screening strategy is applied in China. METHODS: A secondary analysis was
      applied to the surveillance-based longitudinal data of all sputum smear-positive
      TB patients in Prefecture E and Prefecture W of China from 2013 to 2015. The
      population attributable risk (PAR) was estimated using odds ratios for five risk
      factors/predictors and exposure proportions amongst all MDR-TB cases. RESULTS: A
      total of 3513 TB patients (2807 from Prefecture E and 706 from Prefecture W) were
      included. Males accounted for 77.91% (2737/3513) of the patients. The average age
      was 52.5 +/- 20.0 years old. Overall, 40.34% (71/176) of MDR-TB patients were
      from the five high-risk groups during the three-year study period. The detected
      proportion of MDR-TB cases using the high-risk screening strategy was
      significantly higher in Prefecture E than in Prefecture W. The PAR% for all five
      risk factors/predictors was 43.4% (95% CI: 24.6-61.7%), 49.9% (95% CI: 31.3
      67.0%), and 30.3% (95% CI: 12.9-50.1%) in Prefecture E and 36.6% (95% CI: 10.4
      64.5%), 13.3% (95% CI: -1.7-39.7%), and -82.5% (95% CI: -117.5--11.2%) in
      Prefecture W in 2013, 2014, and 2015, respectively. The PAR% for the five
      specific risk factors/predictors ranged from 0.4% (95% CI: -0.2-4.8%) to 21.0%
      (95% CI: 13.1-30.0%) in these two prefectures. CONCLUSION: In general, a high
      risk screening strategy would miss more than half of the MDR-TB patients because
      they do not belong to the five high-risk groups.

PMID- 30203721
TI  - Substance Use in Adults With Type 1 Diabetes in the T1D Exchange.
AB  - PURPOSE: The purpose of the study was to evaluate frequency of use and problem
      use of psychoactive substances in adults with type 1 diabetes (T1D). RESEARCH
      DESIGN AND METHODS: Standardized instruments for assessing tobacco, alcohol, and
      other psychoactive substance use were emailed to 4311 adult participants at 69
      T1D Exchange Registry Exchange Registry centers. A total of 936 respondents (61%
      female, 90% non-Hispanic white, age 38 +/- 16 years) completed the survey.
      RESULTS: In the sample, 166 (18%) reported past-year use of tobacco and 51 (5%)
      reported daily use. Past-year alcohol use was reported by 742 (79%) participants,
      past-month use by 592 (63%), and daily/near-daily use by 87 (9%); 174 (19%) were
      classified as binge drinkers and 93 (11%) as problem drinkers. Nonprescription
      use of another psychoactive substance in the past year was reported by 228 (24%),
      with 167 (18%) indicating they used marijuana, 67 (7%) opioids, 45 (5%)
      sedatives, and 37 (4%) stimulants. Past-year problem use of these substances was
      noted in 31 (3%) respondents. CONCLUSIONS: Adults with T1D in the United States
      use substances at rates that meet or exceed the general population; problematic
      use occurs at rates similar to the general population. These data delineate the
      need to inquire about regular, intermittent, and problematic use of nicotine and
      other substances in individuals with T1D. A better understanding of the impact of
      moderate and occasional use of substances on T1D management and clinical outcomes
      is needed.

PMID- 30203720
TI  - microRNA-935 is reduced in non-small cell lung cancer tissue, is linked to poor
      outcome, and acts on signal transduction mediator E2F7 and the AKT pathway.
AB  - BACKGROUND: A potential role for microRNA-935 (miR-935) has been identified in
      several cancers but not in non-small cell lung cancer (NSCLC). We hypothesised
      changes in miR-935 in NSCLC, and proposed mechanisms that may further explain its
      role in carcinogenesis. METHODS: NSCLC tissue and nearby normal tissue was
      obtained from 101 patients and was probed by qRT-PCR for miR-935 expression. The
      role of miR-935 and a potential target (signal transduction factor E2F7) was
      determined in cell lines by a dual luciferase assay. The function of miR-935 was
      investigated through metabolic activity (MTT) and transwell migration assays.
      Western blot and immunocytochemical assays examined protein expression level.
      Growth of miR-935 transfected or untransfected cells was measured via xenograft
      tumour formation. RESULTS: miR-935 was reduced in cancer tissue and was related
      to lymph node metastases, tumour node metastasis status and poor prognosis (all p
      < 0.02). In vitro, miR-935 suppressed cell proliferation, migration and invasion
      in NSCLC cells through targeting E2F7. Furthermore, E2F7 was upregulated in NSCLC
      tissue associated with poor prognosis (p = 0.0203) of NSCLC patients. miR-935
      suppressed the epithelial-mesenchymal transition and AKT pathways in NSCLC and
      inhibited the tumour growth in vivo. CONCLUSION: Altered miR-935 in lung cancer
      biopsy tissue may be a diagnostic tool and could direct treatment. Involvement in
      carcinogenesis is implied by its suppression of the development of NSCLC via
      targeting E2F7 and inhibiting AKT pathway.

PMID- 30203712
TI  - Emerging PET Radiotracers and Targets for Imaging of Neuroinflammation in
      Neurodegenerative Diseases: Outlook Beyond TSPO.
AB  - The dynamic and multicellular processes of neuroinflammation are mediated by the
      nonneuronal cells of the central nervous system, which include astrocytes and the
      brain's resident macrophages, microglia. Although initiation of an inflammatory
      response may be beneficial in response to injury of the nervous system, chronic
      or maladaptive neuroinflammation can have harmful outcomes in many neurological
      diseases. An acute neuroinflammatory response is protective when activated
      neuroglia facilitate tissue repair by releasing anti-inflammatory cytokines and
      neurotrophic factors. On the other hand, chronic neuroglial activation is a major
      pathological mechanism in neurodegenerative diseases, likely contributing to
      neuronal dysfunction, injury, and disease progression. Therefore, the development
      of specific and sensitive probes for positron emission tomography (PET) studies
      of neuroinflammation is attracting immense scientific and clinical interest. An
      early phase of this research emphasized PET studies of the prototypical imaging
      biomarker of glial activation, translocator protein-18 kDa (TSPO), which presents
      difficulties for quantitation and lacks absolute cellular specificity. Many
      alternate molecular targets present themselves for PET imaging of
      neuroinflammation in vivo, including enzymes, intracellular signaling molecules
      as well as ionotropic, G-protein coupled, and immunoglobulin receptors. We now
      review the lead structures in radiotracer development for PET studies of
      neuroinflammation targets for neurodegenerative diseases extending beyond TSPO,
      including glycogen synthase kinase 3, monoamine oxidase-B, reactive oxygen
      species, imidazoline-2 binding sites, cyclooxygenase, the phospholipase
      A2/arachidonic acid pathway, sphingosine-1-phosphate receptor-1, cannabinoid-2
      receptor, the chemokine receptor CX3CR1, purinergic receptors: P2X7 and P2Y12,
      the receptor for advanced glycation end products, Mer tyrosine kinase, and
      triggering receptor expressed on myeloid cells-1. We provide a brief overview of
      the cellular expression and function of these targets, noting their selectivity
      for astrocytes and/or microglia, and highlight the classes of PET radiotracers
      that have been investigated in early-stage preclinical or clinical research
      studies of neuroinflammation.

PMID- 30203722
TI  - A Functional Tissue-Engineered Synovium Model to Study Osteoarthritis Progression
      and Treatment.
AB  - IMPACT STATEMENT: The synovium envelops the diarthrodial joint and plays a key
      regulatory role in defining the composition of the synovial fluid through
      filtration and biosynthesis of critical boundary lubricants. Synovium changes
      often precede cartilage damage in osteoarthritis. We describe a novel in vitro
      tissue engineered model, validated against native synovium explants, to
      investigate the structure-function of synovium through quantitative solute
      transport measures. Synovium was evaluated in the presence of a proinflammatory
      cytokine, interleukin-1, or the clinically relevant corticosteroid,
      dexamethasone. We anticipate that a better understanding of synovium transport
      would support efforts to develop more effective strategies aimed at restoring
      joint health.

PMID- 30203723
TI  - Robust likelihood inference for diagnostic accuracy measures for paired organs.
AB  - Paired data arise naturally in Ophthalmology where pairs of eyes undergo
      diagnostic tests to predict the presence of certain diseases. The common
      correlation model is popular for modeling the joint probabilities of responses
      from fellow eyes for inference about accuracy measures. One of the assumptions
      underlying the model is exchangeability of fellow eyes that stipulates the
      accuracy measures such as sensitivities/specificities of fellow eyes be equal. We
      propose a parametric robust likelihood approach to testing the equality of
      accuracy measures of fellow eyes without modeling correlation. The robust
      likelihood procedure is applicable for inference about diagnostic accuracy
      measures in general paired designs. We provide simulations and analyses of a data
      set in Ophthalmology to demonstrate the effectiveness of the parametric robust
      procedure.

PMID- 30203724
TI  - Robust Waveform Design of Ultrasound Arrays for Medical Imaging.
AB  - Sound speed is an effective parameter in designing an optimal beamformer. In
      conventional ultrasound imaging systems, the beamformer is designed assuming a
      fixed value of speed, whereas the speed in a tissue is not known precisely and
      also may fluctuate by a great value. The errors in estimating sound speed may
      lead to a severe degradation in the reconstructed image, as mainlobe width and
      sidelobe level of the beampattern are sensitive to the speed variations. In this
      paper, we consider the design of a transmit beamformer, which is robust to the
      speed variations. The problem is formulated as a convex optimization problem
      versus the covariance matrix of the excitation waveforms to obtain a beampattern
      with predefined mainlobe width and a minimum sidelobe level for all possible
      variations of speed. Then, by eigen-analysis of the obtained covariance matrix, a
      set of nonidentical single-carrier short-pulses for the excitation waveforms were
      designed. Various simulations indicate that the proposed method can yield a
      robust beampattern whose mainlobe width and sidelobe level almost remain constant
      by 10% speed variations. In contrast, the beampatterns obtained by nonrobust
      methods suffer extensive changes.

PMID- 30203725
TI  - A novel approach to selecting classification types for time-dependent covariates
      in the marginal analysis of longitudinal data.
AB  - Generalized estimating equations are routinely utilized for the marginal analysis
      of longitudinal data. In order to obtain consistent regression parameter
      estimates, these estimating equations must be unbiased. However, when certain
      types of time-dependent covariates are presented, these equations can be biased
      unless the working independence structure is used. Unfortunately, regression
      parameter estimation can be very inefficient with this structure because not all
      valid moment conditions are incorporated within the corresponding equations.
      Therefore, approaches have been proposed to utilize all valid moment conditions.
      However, these approaches assume that the data analyst knows the type of time
      dependent covariate, although this likely is not the case in practice. Whereas
      hypothesis testing has been used to determine covariate type, we propose a novel
      strategy to select a working covariate type in order to avoid potentially high
      type II error rates with these hypothesis testing procedures. Parameter estimates
      resulting from our proposed method are consistent and have overall improved mean
      squared error relative to hypothesis testing approaches. Existing and proposed
      methods are compared in a simulation study and application example.

PMID- 30203726
TI  - Alert for High Long-term Device Migration Rates Following Endovascular Aneurysm
      Sealing Procedures.

PMID- 30203728
TI  - Preface.

PMID- 30203727
TI  - Cobalt and its compounds: update on genotoxic and carcinogenic activities.
AB  - This article summarizes recent experimental and epidemiological data on the
      genotoxic and carcinogenic activities of cobalt compounds. Emphasis is on the
      respiratory system, but endogenous exposure from Co-containing alloys used in
      endoprostheses, and limited data on nanomaterials and oral exposures are also
      considered. Two groups of cobalt compounds are differentiated on the basis of
      their mechanisms of toxicity: (1) those essentially involving the solubilization
      of Co(II) ions, and (2) metallic materials for which both surface corrosion and
      release of Co(II) ions act in concert. For both groups, identified genotoxic and
      carcinogenic mechanisms are non-stochastic and thus expected to exhibit a
      threshold. Cobalt compounds should, therefore, be considered as genotoxic
      carcinogens with a practical threshold. Accumulating evidence indicates that
      chronic inhalation of cobalt compounds can induce respiratory tumors locally. No
      evidence of systemic carcinogenicity upon inhalation, oral or endogenous exposure
      is available. The scarce data available for Co-based nanosized materials does not
      allow deriving a specific mode of action or assessment for these species.

PMID- 30203729
TI  - Acceptance and Commitment group Therapy for patients with multiple functional
      somatic syndromes: a three-armed trial comparing ACT in a brief and extended
      version with enhanced care - CORRIGENDUM.

PMID- 30203730
TI  - An integrated diagnostic setup for the morphological and molecular identification
      of the Ceratitis FAR complex (C. anonae, C. fasciventris, C. rosa, C. quilicii,
      Diptera, Tephritidae).
AB  - The Ceratitis FAR complex (Diptera, Tephritidae) includes four economically
      important frugivorous flies (Ceratitis anonae, Ceratitis fasciventris, Ceratitis
      quilicii, Ceratitis rosa) whose immature stages and adult females cannot be
      properly resolved through morphological identification. In order to develop a
      simplified molecular tool for the identification of two of these species (C.
      rosa, C. quilicii), we selected a subset of six microsatellite markers out of a
      panel of 16 loci that were previously developed for the molecular differentiation
      of the taxa within the complex. These six markers were first tested in silico and
      then used for the actual genotyping of C. quilicii and C. rosa, resulting in the
      correct identification of all male reference specimens. Here, we propose an
      integrated morphological and molecular setup for the identification of the four
      species of the FAR complex. The decision map relies on preliminary DNA barcoding
      or morphological identification (when possible) to exclude species not belonging
      to the complex followed by (a) morphological identification of all adult male
      specimens and female C. anonae, (b) molecular identification via a panel of 16
      microsatellite markers for immature stages, damaged vouchers and samples
      potentially including adult female C. fasciventris/C. quilicii/C. rosa and (c)
      molecular identification via a reduced panel of six microsatellite markers for
      samples including only C. quilicii and C. rosa. This simplified diagnostic setup
      was profitably implemented in the framework of the ERAfrica fruit fly project and
      will help correctly identify species within the FAR complex for their early
      detection and monitoring.

PMID- 30203731
TI  - Recover recovery style from psychosis: a psychometric evaluation of the German
      version of the Recovery Style Questionnaire (RSQ).
AB  - : AimsThe way an individual handles the experience of psychosis, the so-called
      'recovery style', has been shown to substantially affect long-term outcomes. The
      Recovery Style Questionnaire (RSQ) measures this psychological dimension. The aim
      of this study was to provide a validation of the German version of the RSQ and to
      raise awareness for recovery-oriented approaches. METHODS: The RSQ was translated
      into German according to the guidelines of the WHO and patients were administered
      this questionnaire and measures of internalised stigma, psychotic symptoms,
      illness concept, empowerment, self-esteem and quality of life. Descriptive
      statistics were demonstrated to characterise the sample. Reliability was assessed
      in different forms: internal consistency, test-retest reliability and split-half
      reliability. Items were evaluated with descriptive data and item-total
      correlations. Convergent and discriminant validity were shown, and a confirmatory
      factor analysis was performed. In order to ameliorate the model, a post hoc model
      modification was done. RESULTS: The sample consisted of 138 patients diagnosed
      with schizophrenia spectrum disorders (mean age: 35.7 years; 53.6% men; mean
      duration of illness: 20.6 years) with a mean RSQ overall percentage of 66.12
      (s.d. +/- 17.43%), mainly representing the categories 'mixed picture' and 'tends
      towards integration'. The reliability of the RSQ was acceptable with a Cronbach's
      alpha of 0.741 and a test-retest coefficient of 0.502. Item-total correlations
      were not acceptable for 27 of 39 items. Moderate evidence for convergent validity
      of the RSQ was found. Confirmatory factor analysis revealed that the 13-factor
      model with 39 items originally proposed was partially poorly replicated in the
      present sample (chi2 ratio to degrees of freedom (chi2/df) of 1.732, Comparative
      Fit Index (CFI) of 0.585, Normed Fit Index (NFI) of 0.414, Tucker-Lewis Index
      (TLI) of 0.508, root mean square error of approximation (RMSEA) of 0.095). The
      RSQ was modified based on item-total correlations and path coefficients of the
      single items. The confirmatory factor analysis of the resulting one-factor model
      with 11 items showed adequate fit to the data (chi2/df of 1.562, CFI of 0.936,
      NFI of 0.847, TLI of 0.910, RMSEA of 0.083) and demonstrated good model fit.
      CONCLUSIONS: Despite partially insufficient psychometric data of the original
      RSQ, the concept of recovery style is beneficial to psychiatric research and
      clinical practice. The underlying idea is valuable, and the questionnaire needs
      further development. Therefore, a short version of the RSQ is proposed.

PMID- 30203732
TI  - The debate about renaming schizophrenia: a new name would not resolve the stigma.
AB  - The concept and name of schizophrenia have been questioned in the scientific
      community and among various stakeholders. A name change is seen as a means and an
      opportunity to reduce stigmatizing beliefs and to improve mental health care.
      Some Asian countries have already taken the step of a name change. So far,
      however, the scientific community of western countries has not yet come to an
      agreement on any alternative name. Meeting relevant criteria for a new name,
      finding agreement among all involved groups and replacing the established term is
      a complex process. For now, the concept of schizophrenia has proven its
      reliability, clinical utility and validity, although schizophrenia is a
      stigmatised mental disorder like many others. Renaming cannot be the only answer
      to negative beliefs, prejudice and discrimination.

PMID- 30203733
TI  - Health by design: teaching cleanliness and assembling hygiene at the nineteenth
      century sanitation museum.
AB  - In 1878, amid a rapidly proliferating social interest in public health and
      cleanliness, a group of sanitary scientists and reformers founded the Parkes
      Museum of Hygiene in central London. Dirt and contagion knew no social
      boundaries, and the Parkes's founders conceived of the museum as a dynamic space
      for all classes to better themselves and their environments. They promoted
      sanitary science through a variety of initiatives: exhibits of scientific,
      medical and architectural paraphernalia; product endorsements; and lectures and
      certificated courses in practical sanitation, food inspection and tropical
      hygiene. While the Parkes's programmes reified the era's hierarchies of class and
      gender, it also pursued a public-health mission that cut across these divisions.
      Set apart from the great cultural and scientific popular museums that dominated
      Victorian London, it exhibited a collection with little intrinsic value, and
      offered an education in hygiene designed to be imported into visitors' homes and
      into urban spaces in the metropole and beyond. This essay explores the unique
      contributions of the Parkes Museum to late nineteenth-century sanitary science
      and to museum development, even as the growth of public-health policy rendered
      the museum obsolete.

PMID- 30203734
TI  - Lorenz Oken (1779-1851): Naturphilosophie and the reform of natural history -
      ERRATUM.

PMID- 30203735
TI  - From corps to discipline, part one: Charles d'Almeida, Pierre Bertin and French
      experimental physics, 1840-1880.
AB  - Academic careers in French science during the mid-nineteenth century were made
      within the Universite de France, an integrated state system of secondary and
      higher education controlled by a centralized Parisian educational administration.
      Among the most respected members of the corps universitaire were Charles
      d'Almeida and Pierre Bertin, two historically obscure physiciens whose
      significance derives from their substantial contributions to the social
      organization, teaching and communication of French experimental physics. This two
      part comparative biography uses their entwined careers to make a case for the
      emergence of a discipline of French experimental physics from the corps during
      the tumultuous politico-cultural transition from the Second Empire to the Third
      Republic. Of fundamental importance are disciplinary regimes of teaching and
      inspection within the corps, the foundation of the Societe francaise de physique
      and the Journal de physique, and the diversification of the traditional
      pedagogical role of the Ecole normale superieure, which, from around 1860, began
      to offer a career pathway for aspiring scientific researchers. Having established
      in this paper the socio-institutional mechanisms for the stabilization of a
      distinct field, in part two I characterize the epistemological-methodological
      aspects of French experimental physics.

PMID- 30203736
TI  - Do the adiponectin and leptin levels in preterm and term breast milk samples
      relate to infants' short-term growth?
AB  - Adiponectin and leptin are involved in appetite control and body weight
      regulation. We aimed to evaluate the relationship between breast milk adipokine
      levels and short-term growth of preterm and term infants. Thirty-one preterm
      (median=35.3 weeks) and 34 term (median=38.7 weeks) infants were enrolled. Enzyme
      linked immunosorbent assay was used to detect adipokines in mature milk. Infant
      growth was followed during the first 3 months. Although weight gain in the first
      month was insufficient, positive linear growth was observed in the following
      months for preterm infants, while term infants had positive steady linear growth.
      The median level of adipokines was found to be higher in preterm infants
      (P>0.05). Adiponectin showed significant negative correlations with some
      anthropometric measurements of term infants. However, in preterm infants,
      adiponectin was negatively correlated with length increment and positively
      correlated with body mass index (BMI) increment in the second-third month. In
      addition, leptin was negatively associated with the head circumference at birth
      in preterm infants and the triceps skinfold thickness increment in the first
      second month term infants (P<0.05). In linear regression models, while
      gestational age, adiponectin and leptin were not related, maternal age and pre
      pregnancy BMI had effects on body weight increment in 0-1 months (P<0.05). In
      conclusion, adiponectin may affect short-term growth, while leptin has no
      important effect. It would be beneficial to carry out longitudinal studies to
      evaluate the effects of these adipokines on the growth of infants.

PMID- 30203737
TI  - Patterns and predictors of food texture introduction in French children aged 4-36
      months.
AB  - The aims of this study were to describe which and when food textures are offered
      to children between 4 and 36 months in France and to identify the associated
      factors. An online cross-sectional survey was designed, including questions about
      188 food texture combinations representing three texture levels: purees (T1),
      soft small pieces (T2) and hard/large pieces and double textures (T3). Mothers
      indicated which combinations they already offered to their child. A food texture
      exposure score (TextExp) was calculated for all of the texture levels combined
      and for each texture level separately. Associations between TextExp and maternal
      and child characteristics and feeding practices were explored by multiple linear
      regressions, per age class. Answers from 2999 mothers living in France, mostly
      educated and primiparous, were analysed. Over the first year, children were
      mainly exposed to purees. Soft and small pieces were slowly introduced between 6
      and 22 months, whereas hard/large pieces were mainly introduced from 13 months
      onwards. TextExp was positively associated with children's number of teeth and
      ability to eat alone with their finger or a fork. For almost all age classes,
      TextExp was higher in children introduced to complementary feeding earlier, lower
      for children who were offered only commercial baby foods and higher for those who
      were offered only home-made/non-specific foods during the second year. Our study
      shows that until 12 months of age the majority of French children were exposed to
      pieces to a small extent. It provides new insights to further understand the
      development of texture acceptance during a key period for the development of
      eating habits.

PMID- 30203738
TI  - Antibiotic Resistance Patterns and Molecular Characterization of Methicillin
      Resistant Staphylococcus aureus in Clinical Settings in Rwanda.
AB  - The escalating burden of infections attributable to methicillin-resistant
      Staphylococcus aureus (MRSA) in East African countries is calling for
      interventional strategies to control the spread of this strain. The present study
      aimed at determining the prevalence, antimicrobial profiles, and staphylococcal
      cassette chromosome mec (SCCmec) typing of MRSA strains. This was a cross
      sectional laboratory-based study involving 226 non-duplicated S. aureus isolates
      from different clinical samples of patients attending a referral hospital in
      Kigali. Kirby-Bauer disk diffusion method was used for drug susceptibility
      testing. Methicillin-resistant S. aureus were confirmed using polymerase chain
      reaction (PCR) assay for the mecA gene and SCCmec type PCR assay was used for
      genotyping. Of 138 S. aureus, 39 (31.2%) were found to be MRSA strains. The mean
      age of the patients was 21.9 years. The incidence of MRSA increases with age and
      was 27.1% in patient age group younger than 18 years, 33.3% in the age group
      between 19 and 65 years, and 66.7% in patient age group older than 65 years.
      There was a significant association between geographic regions and incidence of
      MRSA (P = 0.02) with the high MRSA isolates from Northern (61.5%) and Western
      (50%) provinces. Methicillin-resistant S. aureus strains were found to be mostly
      susceptible to linezolid (93.5%). Among the MRSA strains, SCCmec type I and
      SCCmec type IV were the most prevalent at 56.4% and 17.9%, respectively. A high
      prevalence of MRSA was found in Rwanda. Staphylococcal cassette chromosome mec
      type I (52.2%) was the most predominant. A continuous surveillance of MRSA
      strains, particularly in the hospital settings, should be an enduring exercise in
      Rwanda.

PMID- 30203739
TI  - Managing Severe Tetanus without Ventilation Support in a Resource-limited Setting
      in Bangladesh.
AB  - Tetanus, a vaccine-preventable and potentially fatal disease, continues to remain
      prevalent in low- and middle-income countries. Furthermore, physicians are often
      unfamiliar with management of severe tetanus without ventilator support.
      Therefore, we proposed a modified treatment protocol that provides a low-cost and
      effective solution for the management of severe tetanus in resource-constrained
      settings. This is an observational study of 42 patients with severe tetanus
      treated during 2015-2016 at Surya Kanta Hospital, Bangladesh. This facility does
      not have an intensive care unit (ICU), and patients admitted here were provided
      treatment with the modified protocol. A total number of 42 patients with severe
      tetanus were treated with the modified protocol. Among them, 24 (57.1%) recovered
      completely, six (14.3%) recovered with the sequela, and 12 (28.6%) died. Among
      those who recovered with the sequela, four needed mechanical support during
      walking and two had a visual impairment. No significant adverse event was
      recorded during the treatment period. The results gathered during this case
      series provide a sustainable, low-cost, and effective solution to management of
      severe tetanus in resource-constrained settings where ICUs are unavailable.

PMID- 30203740
TI  - Noninvasive Sweat-Based Diagnosis of Visceral Leishmaniasis and Post Kala-Azar
      Dermal Leishmaniasis.
AB  - The diagnosis of visceral leishmaniasis (VL) is one of the foremost barriers in
      the control of this disease, as demonstration of the parasite by splenic/bone
      marrow aspiration is relatively difficult and requires expertise and laboratory
      support. The aim of the present study was to find a noninvasive diagnostic
      approach using the existing recombinant kinesine-39 (rK-39) immunochromatographic
      nitrocellulose strips test (ICT) with a human sweat specimen for the diagnosis of
      VL. The investigation was carried out on specimens (blood, sweat, and urine)
      collected from 58 confirmed VL, 50 confirmed post kala-azar dermal leishmaniasis
      (PKDL), 36 healthy control, and 35 patients from other diseases. The data
      obtained from this study reveal that 96.6% clinically confirmed active VL
      participants were found to be positive when tested against a sweat specimen.
      Interestingly, the scenario was similar when tested against a blood specimen
      (96.6% positive by rK-39). Moreover, a test of both sweats and blood specimens
      from 50 PKDL participants resulted in 100% positivity, whereas no healthy control
      participants were found to be rK-39 positive. The sensitivity of the rK-39 ICT in
      sweat specimen was 94.7%, whereas the specificity was 100% in healthy controls
      from endemic, nonendemic, and other infectious diseases, respectively. No
      difference was observed in sweat specimen of VL and PKDL cases which signifies
      its reliability. However, further evaluation of this method on a larger scale
      could enhance the reliability of the proposed model so that it could be used
      efficiently in VL management and eradication.

PMID- 30203742
TI  - Molecular Detection of Taeniid Eggs in Beetles Collected in an Area Endemic for
      Taenia solium.
AB  - The aim of this study was to demonstrate the presence of Taenia solium eggs in
      beetles collected from sources within the natural environment through molecular
      techniques. Fifty-four pools of beetles were collected in three villages in
      Piura, Peru. DNA was extracted using the FastDNA spin kit for soil. Molecular
      identification of Taenia species was then performed through partial amplification
      of the mitochondrial cytochrome C oxidase subunit I gene. Finally, positive
      samples were sequenced to determine the tapeworm species. Seven positive samples
      were obtained through polymerase chain reaction amplification. Sequencing
      confirmed that two samples were from T. solium and three samples were from Taenia
      hydatigena. The other two samples could not be specifically identified. Our
      findings demonstrate that dung beetles ingest T. solium and T. hydatigena eggs
      under natural conditions and suggest that beetles may play a role in the dynamics
      of transmission of these cestodes.

PMID- 30203741
TI  - Plasmodium vivax Infections in Duffy-Negative Individuals in the Democratic
      Republic of the Congo.
AB  - Although Plasmodium vivax has been assumed to be absent from sub-Saharan Africa
      because of the protective mutation conferring the Duffy-negative phenotype,
      recent evidence has suggested that P. vivax cases are prevalent in these regions.
      We selected 292 dried blood spots from children who participated in the 2013-2014
      Demographic and Health Survey of the Democratic Republic of the Congo (DRC), to
      assess for P. vivax infection. Four P. vivax infections were identified by
      polymerase chain reaction, each in a geographically different survey cluster.
      Using these as index cases, we tested the remaining 73 samples from the four
      clusters. With this approach, 10 confirmed cases, three probable cases, and one
      possible case of P. vivax were identified. Among the 14 P. vivax cases, nine were
      coinfected with Plasmodium falciparum. All 14 individuals were confirmed to be
      Duffy-negative by sequencing for the single point mutation in the GATA motif that
      represses the expression of the Duffy antigen. This finding is consistent with a
      growing body of literature that suggests that P. vivax can infect Duffy-negative
      individuals in Africa. Future molecular and sequencing work is needed to
      understand the relationship of these isolates with other P. vivax samples from
      Asia and South America and discover variants linked to P. vivax virulence and
      erythrocyte invasion.

PMID- 30203743
TI  - Case Report: Monoclonal Gammopathy of Undetermined Significance is Associated
      with Loa loa Infection.
AB  - A 63-year-old woman who migrated from Nigeria to the United States was found to
      have an elevated total serum protein, anemia, and eosinophilia. Serum protein
      electrophoresis (SPEP) and serum protein immunofixation electrophoresis (SPIFE)
      demonstrated monoclonal immunoglobulin G (IgG) kappa restricted bands (IgG 3,820
      mg/dL; kappa/lambda ratio 4.47), indicative of monoclonal gammopathy of unknown
      significance (MGUS). A rapid diagnostic test (RDT) for malaria was positive for
      Plasmodium falciparum (BinaxNOW(r); Alere Scarborough Inc., Scarborough, ME).
      Giemsa-stained blood smears were negative for malarial parasites, however, Loa
      loa microfilariae were identified. Reverse transcription polymerase chain
      reaction for P. falciparum, Plasmodium ovale, Plasmodium malariae, and Plasmodium
      vivax yielded a negative result. She was treated for loiasis with
      diethylcarbamazine and received no malaria medication. Treatment resulted in a
      resolution of the microfilaremia and eosinophilia, a negative RDT for malaria,
      and marked reduction in the monoclonal gammopathy. This is the first reported
      human case of MGUS associated with loiasis and its resolution after antiparasitic
      treatment.

PMID- 30203744
TI  - Case Report: Atypical Cutaneous Leishmaniasis in a Patient with Mixed Leishmania
      guyanensis and Leishmania amazonensis Infection.
AB  - The disseminated form of leishmaniasis is a serious and rare disease, being
      diagnosed in 2% of the cutaneous cases registered per year in Brazil. The main
      characteristic is the appearance of multiple pleomorphic lesions on the cutaneous
      surface. A 68-year-old male from the rural area of Tocantins, Brazil, presented
      atypical disseminated cutaneous leishmaniasis (ACL). The clinical course and
      histopathological and immunological findings presented a mixed pattern that
      hindered diagnosis and therapeutic management. Molecular typing revealed a mixed
      infection with Leishmania (V.) guyanensis and Leishmania (L.) amazonensis.
      Molecular identification of the agents responsible for ACL is important for
      adequate therapeutic planning, minimizing the possibility of sequellae that
      impact the quality of life of the patient.

PMID- 30203746
TI  - Clinical effect of intravenous infusion of zoledronic acid combined with oral
      medication of cinobufagin in the treatment of metastatic bone tumors.
AB  - Aim of the study was to observe and analyze the clinical effect of intravenous
      infusion of zoledronic acid combined with oral medication of cinobufagin in
      treating metastatic bone tumors. The 120 patients who have been treated in the
      hospital for metastatic bone tumor from June 2014 to June 2017 were selected as
      research objects. They were randomly divided into research group and control
      group, each containing 60. The research group was treated with intravenous
      infusion of zoledronic acid combined with oral medication of cinobufagin. In the
      control group, only zoledronic acid intravenous infusion was administered. The
      overall treatment effect of the two groups was observed. The pain of two groups
      was evaluated using numerical rating scale (NRS). The results showed that
      compared with the control group, the research group achieved better clinical
      effect and had a higher quality of life, and the intergroup difference was of
      statistical significance, P<0.05. There was no difference in rate of adverse
      reactions between the two groups, P>0.05, without statistical significance. The
      combined therapy of intravenous infusion of zoledronic acid and oral medication
      of cinobufagin can obtain better therapeutic effect in treating metastatic bone
      tumors.

PMID- 30203745
TI  - Bleaching causes loss of disease resistance within the threatened coral species
      Acropora cervicornis.
AB  - Determining the adaptive potential of foundation species, such as reef-building
      corals, is urgent as the oceans warm and coral populations decline. Theory
      predicts that corals may adapt to climate change via selection on standing
      genetic variation. Yet, corals face not only rising temperatures but also novel
      diseases. We studied the interaction between two major stressors affecting
      colonies of the threatened coral, Acropora cervicornis: white-band disease and
      high water temperature. We determined that 27% of A. cervicornis were disease
      resistant prior to a thermal anomaly. However, disease resistance was largely
      lost during a bleaching event because of more compromised coral hosts or
      increased pathogenic dose/virulence. There was no tradeoff between disease
      resistance and temperature tolerance; disease susceptibility was independent of
      Symbiodinium strain. The present study shows that susceptibility to temperature
      stress creates an increased risk in disease-associated mortality, and only rare
      genets may maintain or gain infectious disease resistance under high temperature.
      We conclude that A. cervicornis populations in the lower Florida Keys harbor few
      existing genotypes that are resistant to both warming and disease.

PMID- 30203747
TI  - Significance of retinol binding protein and prealbumin in neonatal nutritional
      evaluation.
AB  - Neonatal nutritional status means great significance for health, safety and
      thriving growth of neonates. Therefore, clinical evaluation of neonatal
      nutritional status is of great significance. In order to find effective judgment
      basis and curative effect evaluation index that reflect nutritional status of
      neonate. In this study randomly selected 2400 cases of premature infants from
      neonates born during June 2014 - June 2015 as study group, and selected 2000
      normal neonates born in the same period as reference group. A comparative study
      was done on basic situation of the two indexes of retinol binding protein and
      prealbumin of the two groups of neonates. Results showed that retinol binding
      protein index of observation group infants was relatively low, when compared to
      reference group neonates, differences between the two groups P<0.05, with
      statistical significance. Medical personnel timely provided intravenous nutrition
      therapy for observation group infants and measure their index of retinol binding
      protein and prealbumin after 7 days of treatment, finding obvious improvement
      compared to the previous one. Neonatal nutritional status improved significantly,
      with difference between the two groups P<0.05, with statistical value. Hence, it
      is not difficult to conclude that timely index detection of retinol binding
      protein and prealbumin of neonates means important significance for neonatal
      nutrition evaluation, improvement in quality level of neonatal life, and thus is
      recommended to be promoted in clinical application.

PMID- 30203748
TI  - Clinical efficacy of glucosamine hydrochloride tablets in the treatment of
      cervical spondylosis.
AB  - The aim of the stuy was to observe and analyze the effect of glucosamine
      hydrochloride tablets on patients with cervical spondylosis. This study was
      conducted on 130 patients diagnosed with cervical spondylosis who were treated in
      our hospital. The time period was from June 2015 to December 2017. The subjects
      were randomly divided into a reference group treated with cervical vertebra
      exercises and cervical occipital belt traction therapy and the study group was
      further treated with glucosamine hydrochloride tablets. The treatment efficacy of
      both groups was observed. Comparison of the overall treatment efficiency of
      patients showed that compared with the reference group, the study group has more
      significant advantages, P<0.05; comparison of the overall patient satisfaction
      rate showed that the study group was also superior to the reference group,
      P<0.05; In addition, statistical analysis of adverse reactions showed no
      statistically significant difference, P<0.05. The treatment of glucosamine
      hydrochloride tablets in patients with cervical spondylosis can achieve ideal
      results, improve the overall treatment efficiency, and thus, has important
      application significance.

PMID- 30203749
TI  - The efficacy of febuxostat and allopurinol in the treatment of gout with
      hyperuricemia.
AB  - The aim of this research work was to observe and analyze the efficacy of
      febuxostat and allopurinol in the treatment of gout with hyperuricemia. The 160
      patients who has been diagnosed with gout and hyperuricemia in our hospital were
      selected as research objects. They were randomly divided into research group and
      control group, each containing 80. The control group received conventional
      allopurinol treatment, while the research group was treated with febuxostat.
      Then, the treatment efficacy was compared between the two groups. Through
      comparison of blood uric acid levels between the two groups after treatment, it
      can be known that improvement was more significant in the research group, P<0.05.
      The adverse reaction rate in the research group was significantly lower, P<0.05.
      For patients with gout and hyperuricemia, febuxostat therapy has better efficacy
      than that of allopurinol.

PMID- 30203750
TI  - Clinical therapeutic effect and safety of celecoxib in treating knee
      osteoarthritis.
AB  - The clinical therapeutic effect and safety of celecoxib in treating knee
      osteoarthritis were observed. 180 patients who have been confirmed with knee
      osteoarthritis in our hospital were selected as research objects. They were
      randomly divided into research group and control group, each containing 90
      patients. The control group was given with diclofenac sodium therapy, while the
      research group was subjected to celecoxib therapy. The total therapeutic response
      rates between the two groups were observed and compared. The total therapeutic
      response rate of research groups was relatively higher, P<0.05. There was no
      significant difference in pain score, erythrocyte sedimentation rate (ESR),
      quality of life score (QLS) between two groups before treatment, P>0.05. However,
      these indexes of research group were superior then the control group after
      treatment,P<0.05. In addition, the rate of adverse reaction of research group was
      also lower than that of control group, P<0.05. Using celecoxib to treat knee
      osteoarthritis can significantly improve the total therapeutic rate and reduce
      the rate of adverse effect.

PMID- 30203751
TI  - Preparation method of penicillin V potassium beta-cyclodextrin inclusion.
AB  - In order to conceal the unpleasant smell of pharmaceutical raw materials of
      Penicillin V potassium, we use beta-cyclodextrin (beta-CD) as a drug carrier. The
      Penicillin V potassium beta-CD inclusion complex was prepared by saturated
      aqueous solution method; the characterization of penicillin V potassium beta-CD
      inclusion complex is determined by scanning electron microscopy, Differential
      Scanning Calorimeter (DSC) and X-ray Diffraction (XRD), the formation constants
      of the complexes were determined by UV spectrophotometry; based on the results
      obtained from the orthogonal experimental design, the optimum preparation process
      are summarized as follow: beta-CD: Penicillin V potassium = 4: 1 (molar ratio),
      stirring temperature 50 centigrade, stirring time 12h, the encapsulation
      efficiency is 29.40%.

PMID- 30203752
TI  - Clinical effect of cervical paravertebral nerve block combined with Mailuoning
      and Angelica sinensis in treatment of nerve-root type cervical spondylosis.
AB  - To observe and analyze the clinical effect of cervical paravertebral nerve block
      combined with Mailuoning and Angelica sinensis injection in treatment of nerve
      root type cervical spondylosis. 120 patients who have been accepted by our
      hospital for nerve-root type cervical spondylosis were selected as research
      objects. They were randomly divided into a research group and a control group,
      each containing 60 patients. The control group was applied with glucocorticoid
      nerve block therapy, while the research group was treated by cervical
      paravertebral nerve block combined with Mailuoning and Angelica sinensis
      injection. The total therapeutic response rates of two groups were compared. The
      total therapeutic response rate of the research group was relatively
      higher,P<0.05. Through comparing various clinical effect scores between two
      groups, the research group also had advantages over control group, P<0.05. The
      treatment satisfaction degree of the research group was also higher than that of
      control group, P<0.05. The application of cervical paravertebral nerve block
      combined with Mailuoning and Angelica sinensis injection can achieve better
      medical results and achieve higher treatment satisfaction degree.

PMID- 30203753
TI  - Neuroprotective effect of Trichosanthes kirilowii cassia twig on cerebral
      ischemia-reperfusion injury in rats.
AB  - In this study, in-depth observation and investigation of blood-brain barrier
      permeability and neuroprotective effect of Trichosanthes kirilowii cassia twig
      particles on rats with cerebral ischemia-reperfusion injury were performed. Focal
      cerebral ischemia-reperfusion injury model was established by middle cerebral
      artery occlusion method, reperfusion was implemented 2 hours after ischemia;
      qualitative analysis and investigation of trichosanthes kirilowii cassia twig
      particles in plasma, brain tissue and cerebrospinal fluid in normal and middle
      cerebral artery occlusion (MCAO) rats were done by high-performance liquid
      chromatography-tandem mass spectrometry (HPLC-MS/MS); changes in neurological
      deficits, cerebral infarction stereometry, blood-brain barrier permeability and
      histopathological changes of MCAO model rats were observed. Qualitative analysis
      by HPLC-MS/MS results showed that ingredients, paeoniflorin, albiflorin,
      liquiritin in Trichosanthes kirilowii cassia twig particles can reach the brain
      through the blood-brain barrier. In the model group, glycyrrhizin and
      glycyrrhizic acid can be detected in brain tissue or cerebrospinal fluid. In
      addition, Trichosanthes kirilowii cassia twig particles can significantly lower
      neurological deficits of rats in middle cerebral artery occlusion model, reduce
      the Evans blue penetration, contract infarct size, and reduce pathological tissue
      injury of cerebral ischemia reperfusion. The ingredients of Trichosanthes
      kirilowii cassia twig particles can reach the brain tissue through the blood
      brain barrier and play a role in neuroprotection of rats with cerebral ischemia
      reperfusion injury, which has important research significance and brings
      scientific experimental, theoretical basis for clinical drug use.

PMID- 30203754
TI  - Clinical effect of sequential therapy with azithromycin in children mycoplasma
      pneumoniae pneumonia.
AB  - In the present study, the clinical effect of Sequential Therapy with Azithromycin
      in children mycoplasma pneumoniae pneumonia is observed and analyzed. The 160
      children who were diagnosed as mycoplasma pneumoniae pneumonia were selected as
      subjects. They were randomly divided into two groups: study group and reference
      group and each group with 80 cases. Among them, the children in study group were
      carried out sequential therapy of erythromycin and the sequential therapy of
      azithromycin in reference group. The overall treatment efficiency, the incidence
      of adverse reactions, the time of symptom recovery and hospitalization were
      compared between the two groups. Through comparing the efficiency of overall
      treatment between two groups, the study group has more significant advantages
      than reference group: P<0.05; through comparing the time of symptoms recovery and
      hospitalization, study group is significantly less than reference group: P<0.05;
      in addition, through comparing the incidence of adverse reactions, the difference
      between two groups is not obvious: P>0.05. For sequential therapy of azithromycin
      in children mycoplasma pneumoniae pneumonia, it can achieve good therapeutic
      effect and has no serious adverse reactions, which has tremendous applied values.

PMID- 30203755
TI  - Analysis of ultrasonic atomized inhalation of antibiotics in infant pneumonia
      treatment.
AB  - To observe and analyze the specific nursing pattern for ultrasonic atomized
      inhalation of antibiotics in infant pneumonia treatment, 200 children with
      pneumonia treated in our hospital were enrolled as the study subjects. All the
      patients were treated with ultrasonic atomized inhalation of antibiotics. The
      children were divided into a reference group treated with general conventional
      nursing and a study group treated with targeted nursing. The nursing effect was
      compared in the two groups. Observation of overall treatment efficacy of the two
      groups showed that the study group is superior to the reference group, P<0. 05;
      comparison of the recovery time of clinical symptoms and signs between the two
      groups showed that the study group needs a shorter time to restore cough, fever,
      asthma, and lung rales. P<0.05; the self-developed satisfaction questionnaire
      survey shows a higher satisfaction in the study group, P<0.05. In infant
      pneumonia treatment with ultrasonic atomized inhalation of antibiotics, targeted
      nursing patterns should be adopted to improve overall treatment efficacy.

PMID- 30203756
TI  - Clinical efficacy and ultrasound inspection of the treatment of hypertensive
      heart patients with Valsartan combined with hydrochlorothiazide.
AB  - To observe and analyze the clinical efficacy and ultrasound detection results of
      treatment of hypertensive patients with heart disease with valsartan combined
      with hydrochlorothiazide. The 160 hypertensive patients with heart disease who
      were treated in our hospital were selected as study subjects and randomly divided
      into study group and reference group, each with 80 patients. Where, the reference
      group was solely treated with valsartan, while the study group received
      hydrochlorothiazide treatment on this basis. The therapeutic effects of the two
      groups were observed and analyzed. Comparison of the overall treatment efficacy
      and incidence of adverse reactions between the two groups showed that the study
      group had more significant advantages than the reference group, P<0.05; in
      comparison of systolic blood pressure and diastolic blood pressure after
      treatment between the two groups, the study group had higher improvement degree
      than the reference group, P<0.05; ultrasonic ECG inspection showed that the study
      group was superior to the reference group with better recovery in indexes
      including left ventricular mass index, left ventricular posterior wall thickness,
      left ventricular ejection fraction, P<0.05. The combination of Valsartan and
      hydrochlorothiazide for hypertensive patients with heart disease can
      significantly improve the treatment effect and significantly reduce the incidence
      of adverse reactions. Therefore, it is worthy of popularization and application.

PMID- 30203757
TI  - Observation of curative effect of nasal continuous positive airway pressure
      combined with high-dose ambroxol for neonatal respiratory failure.
AB  - To observe and analyze the effectiveness of nasal continuous positive airway
      pressure for neonatal respiratory failure. The 200 newborns with respiratory
      failure treated in our hospital. They were enrolled as study subjects and
      assigned to study group and reference group with equal number of cases. The study
      group was treated with continuous positive airway pressure plus high-dose
      ambroxol, while the reference group only received high-dose ambroxol. The overall
      treatment effect was compared between the two groups. Observation of the overall
      treatment efficacy of the study group and the reference group showed that the
      study group was superior to the reference group, P<0.05; comparison of such
      treatment indicators as disappearance of shortness of breath, disappearance of
      cyanosis, disappearance of groaning, assisted ventilation duration, hospital stay
      showed that the study group was significantly superior to the reference group,
      P<0.05; comparison of arterial oxygen partial pressure, oxygen saturation, and
      carbon dioxide partial pressure showed differences between groups, P<0.05.
      Treatment of neonatal respiratory failure with nasal continuous positive airway
      pressure plus high-dose ambroxol can achieve good results and reduce hospital
      stay.

PMID- 30203758
TI  - Clinical effect of lamivudine in treating liver function lesion caused by
      hepatitis B combined with Anti-TB drugs.
AB  - The present study is designed to conduct, the analysis on the curative effect of
      Lamivudine in treating liver function lesion caused by hepatitis B combined anti
      TB drugs. The 4200 patients who have been treated for hepatitis B combined with
      pulmonary TB in 8 different hospitals from Feb 2014 to Feb 2016 were selected as
      research objects. They were randomly divided into control group and observation
      group, each containing 2100 patients. In control group, patients were applied
      with conventional Anti-TB therapy and liver-protecting therapy; while in
      observation group, patients were applied with lamivudine in addition to
      conventional therapies. The variations of liver functions of both groups before
      and after therapies were observed. After treatment, the liver function lesions of
      patients in observation group were significantly lower than that in control
      group; moreover, the drug withdrawal rates of patients in control group were
      significantly higher. There was statistical difference between both group,
      P<0.05. In the process of treating patients with liver function lesions caused by
      hepatitis B combined with anti-TB, applying Lamivudine on the basis of
      conventional liver protection therapy and anti-TB therapy can effectively inhibit
      HBV replication, and prevent liver disease from getting worse, so as to reduce
      the liver function lesions in treating patients with hepatitis B combined with
      anti-TB and accelerate rehabilitation.

PMID- 30203759
TI  - CT-guided drug injection around the nerve root to treat lumbar disc herniation.
AB  - To observe and analyze the effect of CT-guided drug injection around the nerve
      root in the treatment of lumbar disc herniation, the 140 patients diagnosed with
      lumbar disc herniation in our hospital, were selected as the study subjects for
      CT-guided drug injection around the nerve root and treatment efficacy was
      observed. According to the modified Mac Nab criteria, there were 80 cases, 50
      cases, 6 cases, and 4 cases of excellent, good, fair, and poor results, with
      excellent and good rate at 92.86%; the patients whose onset time was less than
      three months and more than three months were compared in terms of VAS scores
      before and after surgery. The results showed that the postoperative pain score
      was significantly lower in patients whose onset time was less than three months
      compared to those whose onset time was more than three months, P<0.05;
      observation of patients' quality of life before and after treatment shows great
      improvement in quality of life after treatment, P<0.05. The treatment of lumbar
      disc herniation with CT-guided drug injection around the nerve root can achieve
      relatively good results with significantly improved therapeutic effect and great
      application value.

PMID- 30203760
TI  - Clinical effect of total thyroidectomy combined with radioactive iodine in
      thyroid cancer treatment.
AB  - Aim of this research work is to observe and analyze the clinical effect of total
      thyroidectomy combined with radioactive iodine in thyroid cancer treatment. The
      120 thyroid cancer patients treated in our hospital were enrolled as study
      subjects and assigned to study group (treated with total thyroidectomy and
      radioactive iodine) and reference group (treated with conventional total
      thyroidectomy). The overall treatment efficacy was compared between the two
      groups. Comparison of overall treatment efficacy of the two groups showed that
      the study group has superior results to the reference group (P<0.05). Comparison
      of incidence of recurrent laryngeal nerve injury in the two groups revealed no
      significant differences, P>0.05. However, in life quality assessment, the study
      group was significantly superior to the reference group in terms of physiological
      function, psychological function, social function, and overall life quality
      scores, P<0.05. Total thyroidectomy combined with radioactive iodine can well
      improve the overall treatment efficiency and enable patients to have higher
      quality of life at the same time.

PMID- 30203761
TI  - Therapeutic effect of chlorpheniramine in treatingupper airway cough syndrome
      (UACS) and chronic rhinitis/sinusitis.
AB  - This paper aims to analyze the specific effect of chlorpheniramine on upper
      airway cough syndrome is related to its treatment of chronic rhinitis and
      sinusitis. A total of 218 patients admitted to hospital between March 2014 and
      June 2016 were treated with chlorpheniramine. The patients were divided into two
      groups based on treatment effect in follow-up visits (all were effective):
      effective group (114 cases, 52.29%) and ineffective group (104 cases, 47.71%).
      The proportion of complicated rhinitis or sinusitis of the two groups were
      compared, and improvement effect on clinical symptoms of chronic rhinitis and
      sinusitis after treatment was compared. The probability of rhinitis / sinusitis
      was 65.79% (75/114) in the effective group and 69.23% (72/104) in the ineffective
      group. There was no statistical difference between the two groups (P>0.05). In
      both effective and ineffective group, the symptoms such as chest tightness and
      shortness of breath and pharyngeal discomfort were improved to a certain extent,
      and the effective group had better improvement effect, but there was no
      statistical difference between the two groups (P>0.05). In addition, there was no
      correlation between improvement of cough and improvement of symptoms in the
      effective group, 21 cases of cough disappeared completely, while complete
      disappearance rate of other symptoms was only 57.15% (12/21). Chlorpheniramine is
      effective to some extent in treatment of upper airway cough syndrome, but
      chlorpheniramine in treatment of upper airway cough syndrome is not associated
      with rhinitis/sinusitis treatment.

PMID- 30203762
TI  - Comparison of clinical effect in treatment of bone tumor between zoledronic acid
      needle and ibandronate needle.
AB  - To observe and analyze the clinical effect of zoledronic acid needle and
      ibandronate needle in treatment of bone tumor. 100 patients who have been treated
      in our hospital for bone tumor were selected as research objects. They were
      randomly divided into research group and control group, each containing 50
      patients. The research group was applied with ibandronate needle therapy, while
      the control group was given with zeledronic acid needle therapy. After treatment,
      the clinical effects of the two groups were observed and analyzed. Through
      comparing the pain relief rate after treatment between the two groups, it can be
      known that the pain relief rate of research group was relatively higher, P<0.05;
      the rate of adverse effect in research group was relatively lower, P<0.05; the
      quality of life score (QLS) of research group was significantly superior to that
      of control group, P<0.05. theibandronate needle therapy is a more reliable and
      superior method in treatment of bone tumor compared with zoledronic acid needle
      therapy, which should be promoted in clinical treatment.

PMID- 30203764
TI  - Trimetazidine ameliorates myocardial ischemia-reperfusion injury.
AB  - Aim of this study was to investigate the effects of trimetazidine attenuating the
      myocardial ischemia-reperfusion injury to myocardium in rats and the underlying
      mechanisms. A model of myocardial ischemia reperfusion was established via
      ligating the left anterior descending coronary artery in 30 rats, and then they
      were randomly assigned to model group (n=10), low dose group (n=10) and high dose
      group (n=10). Moreover, additional 10 rats were collected and allocated to sham
      operation group, which was served as control group. Then, rats in the low dose
      group and high dose group were given trimetazidine with the dose of 10mg/kg and
      30mg/kg respectively by intragastric administration, while rats in the control
      group and model group were given the equivalent volume saline. The dose was given
      once a day for consecutive 4 weeks in all rats. Echocardiography was applied to
      evaluate cardiac function, including left ventricular end-systolic dimension
      (LVESD), left ventricular end diastolic dimension (LVEDD) and left ventricular
      ejection fraction (LVEF). Next, myocardial tissue was collected, and Bax and Bcl
      2 mRNA and the protein levels in the four groups were detected by RT-PCR and
      Western blot respectively. The level of malonaldehyde (MDA) and super oxide
      dismutase (SOD) activity in rat myocaridum in each group were detected by
      colorimetric methods, while the variables of apoptosis were measured by TUNEL
      methods. In comparison with the control group, LVEDD, LVEDS of rats increased
      significantly, LVEF decreased obviously, as well as Bax level, MDA level and the
      apoptotic variables in myocardial tissue increased (P<0.05), but Bcl-2 level and
      SOD activity decreased significantly in low dose, high dose and model group
      (P<0.05). Compared with model group, LVEDD, LVEDS of rats decreased obviously,
      LVEF increased significantly, as well as Bax level, MDA level and the apoptotic
      variables in myocardial tissue decreased (P<0.05), but Bcl-2 level and SOD
      activity increased significantly in low dose group, high dose group (P<0.05). The
      regulatory role of trimetazidine on above indicators of rats was in a dose
      dependent manner. Trimetazidine can ameliorate rat myocardium following ischemia
      reperfusion injury by effectively attenuating the injury from myocardial cell
      apoptosis; meanwhile, it can resist cell apoptosis through regulating Bax and bcl
      2 expression, which exhibits guiding significance for the treatment of myocardial
      ischemia and reperfusion.

PMID- 30203763
TI  - Observing the effect of traditional Chinese medicine Kouchuang Xiaotong powder on
      patients with recurrent aphthus ulcer.
AB  - The effect of traditional Chinese medicine Kouchuang Xiaotong powder on patients
      with recurrent aphthous ulcer is observed and analyzed. 140 patients with
      recurrent aphthous ulcer in our hospital were selected as research objects, which
      were randomly divided into two groups: study group and control group. Among them,
      the patients in study group were treated with traditional Chinese medicine
      kouchuang xiaotong powder, and patients in control group were given the general
      routine treatment, comparing overall effective treatment of the two groups.
      Through comparing the time of pain disappearance, the size of ulcer after
      treatment, ulcer healing time and the time of feeding improvement, the results
      showed that study group had more obvious advantages than control group with
      P<0.05; through comparing pain score and overall curative effect of the two
      groups, study group was significantly superior than control group with P<0.05.The
      treatment of traditional Chinese medicine Kouchang Xiaotong powder on patients
      with recurrent aphthous ulcer, it can obtain good effect, significantly improve
      the curative effect and promote recovery as soon as possible.

PMID- 30203765
TI  - Analysis of phenytoin drug concentration for evaluation of clinical response,
      uncontrolled seizures and toxicity.
AB  - The narrow therapeutic index, non-linear pharmacokinetics and unpredictable
      absorption require regular therapeutic monitoring of phenytoin. The influence of
      genetic differences, sex, age and race on the phenytoin plasma levels and its
      metabolites is well recognized. This study is aimed at evaluating phenytoin
      plasma drug concentration and its relationship with clinical response, persistent
      seizures and toxicity in different gender and various age groups of Chinese
      epileptic patients. This knowledge will help the clinicians in adjusting the drug
      dosages of phenytoin in various sub-groups of epileptic patients for enhancing
      the safety, efficacy and minimizing the toxicity of phenytoin. A total of 48
      plasma samples of epileptic patients for measuring the plasma phenytoin
      concentration were received. Only patients displaying persistent seizures or
      suspected of adverse effects were requested for drug monitoring. All these
      samples were analyzed for therapeutic drug monitoring with Enzyme-multiplied
      immunoassay technique. Surprisingly, it was found that majorities (85.5%) of
      samples were out of the reference range, of which 69% of samples were in sub
      therapeutic levels and 16.5% of samples were above therapeutic levels. Only 14.5%
      of all samples had phenytoin levels in the therapeutic range. The difference in
      plasma concentration of phenytoin was notably altered in gender and various age
      groups. Careful attention must be applied to specific gender and particular age
      group on an individual basis in the interpretation of plasma concentration
      results, in order to facilitate the modification of doses and develop the best
      approach in treatment and to obtain the desired clinical response because
      multiple factors can affect the phenytoin plasma concentration. Through these
      results, it can be concluded that a good correlation exists between phenytoin
      plasma concentration and clinical response. Therefore, regular therapeutic
      monitoring of phenytoin and screening of HLA-A, B, C and DRB1 genotypes before
      prescribing phenytoin in epileptic patients is essentially required to achieve
      maximum clinical response and prevent the serious toxicity.

PMID- 30203766
TI  - Evaluation of the drug effect and rational use of antiseptic drugs in outpatient
      and emergency department of hospital.
AB  - With the popularization and application of antiseptic drugs, the abuse of
      antiseptic drugs and various unreasonable applications have also become a serious
      medical problem. The prescriptions of antibiotics in our hospital were randomly
      selected for statistical analysis. Further, we analyzed the various situations of
      the use of antibiotics in outpatient department, and calculated the DDDs of
      different drugs based on the defined daily dose (DDD). The results showed that
      there were 403 unreasonable prescriptions, accounting for 24.9% of the drug
      prescriptions. The main problems of irrational prescriptions were unsuitable
      drugs, non indications and improper frequency of administration, which accounted
      for 27.1%, 21.3% and 18.3%. It is suggested that the quality department of the
      hospital should strengthen the special training for rational use of antimicrobial
      agents, intervene in time and effectively, and gradually change post evaluation
      into prevention and intervention in advance.

PMID- 30203767
TI  - Effect of gatifloxacin in the treatment of ophthalmological diseases and
      continuous nursing intervention.
AB  - Gatifloxacin is a fourth-generation antibiotic and its antibacterial activity is
      better. It can play an obvious antiseptic effect in gram-positive bacteria,
      mycobacterium, mycoplasma, anaerobes and chlamydia. This study analyzed the
      treatment of the foreign body of the cornea by gatifloxacin eye drops. The
      results showed that gatifloxacin has a high bacterial clearance rate, which can
      reach 96.1%. The clinical effect is accurate and the adverse reaction is less.
      Compared with the control drug levofloxacin, its efficacy and safety were not
      statistically significant. Moreover, MIC determination of bacteria isolated from
      the study showed that gatifloxacin had stronger antibacterial activity. At the
      same time, it can be seen that nursing intervention can effectively improve the
      satisfaction of the treatment, before the operation, the patient's eye
      abnormalities, the psychological status of the patient, and the suitability of
      drug allergy should be evaluated.

PMID- 30203768
TI  - Effect of traditional Chinese medicine Bupleurum in the treatment of influenza A
      (H1N1).
AB  - The treatment of influenza A (H1N1) is mainly antiviral treatment, symptomatic
      treatment or traditional Chinese medicine treatment. Previous studies showed that
      the extract of Bupleurum has the functions of anti-inflammatory, antiviral,
      regulating the immune system and so on, which can be used to treat influenza. In
      this paper, we analyze the drug effect of bupleurum compound medicine, at the
      same time, using oseltamivir as control group. The results showed that the
      Chinese medicine chima qingwen decoction had certain antiviral effects. No
      adverse reactions occurred during the treatment period, and the overall effective
      rate was 93.3%. It shows that combination therapy of Chinese and Western medicine
      is feasible for mild cases of influenza A (H1N1). Therefore, the research and
      development of Chinese medicine preparations has positive research significance
      and sufficient market potential.

PMID- 30203769
TI  - Effect of baicalein with different concentrations on myocardial ischemia
      reperfusion injury in rats.
AB  - Baicalein is a kind of flavonoids. Long term use of flavonoids can reduce blood
      pressure by releasing physiological NO to keep the vascular endothelial function
      of hypertensive animals and reduce myocardial ischemia injury. The purpose of
      this study is to explore the effect of baicalein on myocardial I/R damage and
      explore its mechanism of action, so as to provide experimental evidence for
      treatment. The results show that baicalein has a significant improvement in I/R
      damage, mainly in reducing myocardial infarction rate, reducing the release of
      myocardial isozyme LDH and CK, reducing the level of oxidative stress and
      reducing the apoptosis of cardiac myocytes. In the baicalein group, the
      myocardial ischemia state of isolated rat hearts was improved. Among them,
      myocardial infarction rate in low and middle concentration group was
      significantly decreased (P<0.05 or P<0.01), and there was no significant change
      in high concentration group (P>0.05). The apoptosis rate of cardiac myocytes in
      the isolated group of baicalein was significantly decreased (P<0.01). The role of
      baicalein in the cardiovascular system needs further test and clinical research.

PMID- 30203770
TI  - Comparison and analysis of statins drug use in the treatment of diastolic
      dysfunction in patients.
AB  - Statins have multiple anti lipid effects, such as anti-inflammatory, anti
      oxidation and anti arteriosclerosis, which are beneficial to improve cardiac
      function. Statins can effectively improve left ventricular remodeling and protect
      ventricular diastolic function. In this study, the effects of statin therapy on
      diastolic function and BNP level and exercise tolerance after exercise were
      observed by statins in patients with diastolic dysfunction. The results showed
      that after atorvastatin treatment, the exercise BNP decreased in the treatment
      group, which was significantly different from that before treatment and in the
      control group (P<0.05). This study demonstrated that atorvastatin was used to
      treat patients with diastolic dysfunction and exercise hypertension by lowering
      blood pressure and reducing exercise SBP, anti-inflammatory and improving
      vascular endothelial function.

PMID- 30203771
TI  - Effect of doxycycline and atorvastatin on improving exercise tolerance in
      patients with angina pectoris.
AB  - The therapeutic effect of statins on the stabilization of atherosclerotic plaques
      has been affirmed. In recent years, the inhibition of matrix metalloproteinases
      (MMPS) of tetracycline drug doxycycline has attracted more and more attention. In
      this paper, we observed the effect of atorvastatin and doxycycline on exercise
      tolerance in patients with stable angina pectoris. The results showed that there
      was no significant difference in the clinical efficacy of the two groups and the
      effect on the exercise tolerance (P<0.05). There were 4 cases of mild
      gastrointestinal reaction in the doxycycline group and no other serious adverse
      reactions. The total effective rate of treatment in the doxycycline group was
      93.3%. Doxycycline treatment significantly reduced the frequency of angina
      pectoris and the incidence of cardiovascular events, and the treatment effect was
      better. To sum up, we think doxycycline is a safe, cheap, therapeutic drug to
      stabilize plaque.

PMID- 30203772
TI  - Comparison and analysis of the therapeutic effect of different statins in the
      treatment of atherosclerosis.
AB  - Studies have confirmed that lipid-lowering drugs can effectively control the
      morbidity and mortality of cardiovascular and cerebrovascular diseases and
      statins are the most widely used. The aim of this study is to investigate the
      effect and mechanism of different statins on atherosclerotic patients. The
      patients were randomly divided into 4 groups according to the digital method, and
      the patients were treated with conventional therapy, simvastatin treatment,
      pravastatin treatment, atorvastatin treatment. It is concluded that statins are
      safe, effective and reliable for the treatment of atherosclerosis, and worthy of
      clinical promotion. The results also showed that after 6 months of taking
      statins, the levels of NO and NOS increased, the thickness of carotid intima
      media became thinner and the plaque score decreased. This study provides a basis
      for elucidating the role of statins in the body.

PMID- 30203773
TI  - Adverse reaction and rational use of paracetamol tablets and its drug content
      detection based on spectral test.
AB  - Paracetamol and amantadine hydrochloride tablet is a commonly used drug to
      relieve the common cold. Its main ingredient is 4-Acetamidophenol. The safety of
      acetaminophen containing cold drugs has attracted more and more attention in
      recent years. In order to promote the clinical safety of drugs, the adverse
      reaction and clinical application of acetaminophen drugs are analyzed in this
      paper. The adverse reactions induced by acetaminophen mainly include: allergic
      reaction (46.1%), liver and kidney injury (25%), blood system (15.7%) and
      digestive system (5.2%). At the same time, we tested the content of acetaminophen
      by using spectral test. It can be seen that the method can be extended to the
      quantitative analysis and quality control of the effective components of other
      compound drugs.

PMID- 30203774
TI  - Drug effect analysis of sorafenib combined with transcatheter arterial
      chemoembolization in the treatment of advanced hepatocellular carcinoma.
AB  - Sorafenib is a new multi-target oral drug that inhibits many kinds of protein
      kinase small molecules to treat tumors. Currently, sorafenib is one of the drugs
      that permit systemic treatment of liver cancer in the middle stage. Although
      sorafenib has good therapeutic effect on liver cancer, the clinical effect of
      sorafenib alone in the treatment of liver cancer is limited. This study compared
      the efficacy of sorafenib, TACE (transcatheter arterial chemoembolization), and
      sorafenib combined with TACE in the treatment of liver cancer patients. The
      results showed that the curative effect of sorafenib combined with transcatheter
      arterial chemoembolization is better than that of hepatic artery
      chemoembolization or sorafenib orally. The total effective rate of combined
      treatment is 93.8%, while the effective rate of arterial chemoembolization and
      sorafenib is 64.1% and 72.2% respectively. Combined treatment can significantly
      prolong the total survival of the patients with liver cancer, which is
      significantly different from that of arterial chemoembolization or sorafenib
      alone.

PMID- 30203775
TI  - Analysis of the drug therapy of gatifloxacin and levofloxacin in the treatment of
      acute bacterial conjunctivitis.
AB  - Acute bacterial conjunctivitis is an acute conjunctivitis that is frequently
      transmitted in summer and autumn. It is a common and frequently occurring disease
      in ophthalmology clinic. Gatifloxacin is an effective antibacterial drug. It not
      only maintains the antibacterial effect of the three generation of
      fluoroquinolones on Gram-negative bacteria, but also enhances the effectiveness
      of gatifloxacin, including other Gram-positive bacteria and anaerobes. In this
      paper, by taking gatifloxacin eye drops as the experimental drug and levofloxacin
      as the control drug, we conducted a double-blind randomized controlled clinical
      trial to evaluate the efficacy and safety of gatifloxacin eye drops in the
      treatment of acute bacterial conjunctivitis. The clinical results showed that the
      total effective rate of the Gatifloxacin treatment group was 95%. Conclusion
      shows that gatifloxacin is a safe and effective antibiotic eye drops. It has
      broad antibacterial spectrum, strong antibacterial activity and effective
      clinical treatment, and it can effectively treat acute bacterial conjunctivitis.

PMID- 30203776
TI  - Effect of atorvastatin on the apoptosis of human umbilical vein endothelial cells
      and its drug mechanism.
AB  - Recent studies have shown that statins can inhibit the apoptosis of vascular
      endothelial cells. Many pharmacological actions of statins have nothing to do
      with their cholesterol lowering effects. These effects are called non lipid
      lowering cardiovascular protective effects. In this study, by establishing a high
      glucose induced vascular endothelial cell apoptosis model, we explored the
      mechanism of the non lipid - related cardiovascular protective effect of
      atorvastatin. The results showed that atorvastatin could protect human umbilical
      vein endothelial cells from damage induced by new high glucose and inhibit
      apoptosis. High concentration atorvastatin can up regulate the expression of Bcl
      2 and down regulate the expression of Bax protein (P<0.05). This suggests that
      statins may play a role in cardiovascular protection by inhibiting endothelial
      cell apoptosis. This result is confirmed by experiments, which can provide clues
      for clinical treatment, and combine drug therapy and lifestyle intervention to
      reduce blood sugar.

PMID- 30203777
TI  - Effectiveness of Radix astragali and Salvia miltiorrhiza injection in treatment
      of skeletal muscle injury of aerobics athletes.
AB  - This paper aims to observe and analyze the effects of Radix astragali and Salvia
      miltiorrhiza on skeletal muscle injury of aerobics athletes. In this study, 600
      cases of aerobics athletes with skeletal muscle injury were randomly divided into
      experimental group and control group according to different treatment regimens,
      and the number of cases was the same, each with 300 cases. The control group was
      given local massage and rehabilitation training. On the basis of the above, Radix
      astragali and Salvia miltiorrhiza injection was given to the experimental group.
      The indicators of overall treatment efficiency, improvement of serum SOD level,
      improvement of serum MDA content, comparison of plasma creatine kinase (CK) and
      myoglobin (Mb) were observed and compared between the two groups. After
      implementation of different treatment programs, in comparison of overall
      treatment efficiency, the experimental group is significantly superior to the
      control group (P <0.05); in comparison of improvement of serum SOD level,
      improvement of serum MDA content, the experimental group is superior to the
      control group(P <0.05). In addition, in comparison of plasma creatine kinase (CK)
      and myoglobin (Mb) level, the experimental group is significantly superior to the
      control group(P <0.05). It is very important for aerobics athletes with skeletal
      muscle injury to take active and effective therapy to recover as soon as
      possible. The program of Radix astragali and Salvia miltiorrhiza injection has
      obvious effect, which can promote athletes' skeletal muscle injury repair and
      improve the overall treatment efficiency, which is worth popularizing in
      practice.

PMID- 30203778
TI  - Therapeutic drug monitoring of valproic acid.
AB  - The unpredictable and unfavorable connection of dose and plasma concentration of
      valproic acid supports the necessity to regularly measure its plasma
      concentration. The present study is drug monitoring of valproic acid and
      comparative evaluation of therapeutic monitoring results of valproic acid for
      assessment of clinical response, safety and toxicity in different age and gender
      groups of Chinese epileptic patients. This knowledge will help the clinicians in
      adjusting the drug dosages of valproic acid in various sub-groups of epileptic
      patients for enhancing the safety and minimizing the toxicity of valproic acid. A
      total of 206 plasma samples (126 males and 80 females) of epileptic patients
      using valproic acid were requested for therapeutic drug monitoring by neurology
      department of Qilu Hospital. It was found that 29 % of the total samples were
      found in sub-therapeutic levels, 13% of the samples had toxic levels and 58% of
      all the samples had valproic acid levels in therapeutic range. The difference in
      plasma concentration of valproic acid is notably altered in gender and various
      age groups. However, this requires further investigation. Despite the majority of
      samples in the therapeutic range, there was an unfavorable clinical response. The
      outcomes of the current research work exposed that there was a poor correlation
      between the plasma concentration and clinical response. Careful attention must be
      applied to specific gender and particular age group on an individual basis in the
      interpretation of plasma concentration results, in order to facilitate the
      modification of doses and develop the best approach in treatment and to obtain
      the desired clinical response because multiple factors can affect the valproic
      acid plasma concentration. Through these results, it can be concluded that poor
      correlation exists between valproic acid plasma concentration and clinical
      response.

PMID- 30203779
TI  - Iodine status of pregnant women in Northern Cyprus

PMID- 30203780
TI  - Comparison of Scoring Systems in Predicting Success of Percutaneous
      Nephrolithotomy.
AB  - BACKGROUND: Scoring systems (SS) are useful to inform the patients about the
      success and complication rates of the operation prior the surgery. AIMS: We aimed
      to determine the applicability of the popular SS (Guy's, S.T.O.N.E and CROES) by
      means of examining preoperative data of patients treated with percutaneous
      nephrolithotomy (PNL). STUDY DESIGN: Cross sectional. METHODS: We retrospectively
      reviewed files of the patients who had undergone PNL in our center between 2011
      and 2015. Excluded from the study were patients aged < 18 years, and those who
      were not assessed preoperatively with computed tomography (CT). Preoperative CT
      images of all patients were assessed by a single observer (MT), and patients were
      graded based on three SS. Demographic data were analyzed along with perioperative
      data (operation, fluoroscopy, length of hospital stay, changes in hematocrit
      values, location, and number of access sites, stone-free and complication rates).
      RESULTS: A total of 298 patients who had been treated with 300 procedures were
      enrolled into the study. Mean age, stone burden, number of stones, and density
      were 48.1+/-12.9 years, 663.5+/-442.8mm2, 1.8+/-1.1 and 888.3+/-273 HU
      respectively. Scores of the cases based on Guy's, S.T.O.N.E, and CROES SS were
      calculated as 2, 7.6, and 222,1 points respectively. 81.6% of the patients were
      stone-free. Complications were detected in 30 (9.9%) patients. Based on ROC curve
      analysis a positive correlation was detected between success rate and scoring
      systems, i.e., Guy's (p:<0.001, r:-0.309), S.T.O.N.E. (p:<0.001, r:-0.295), and
      CROES (p:<0.001, r:0.426). The CROES scoring system had the highest predictive
      value. The sensitivity rates rates for Guy's, Croes and Stone SS were as 78.78%,
      80% and 82.34% respectively. CONCLUSION: Our results show that all of SS
      predicted correctly the success of the PNL procedures. The CROES scoring system
      had the highest predictive value.

PMID- 30203781
TI  - Tumoral Melanosis Arising on a Mycosis Fungoides Plaque

PMID- 30203782
TI  - Low temperature photoconductivity of few layer p-type tungsten diselenide (WSe2)
      field-effect transistors (FETs).
AB  - We report on the low-temperature photoconductive properties of few layer p-type
      tungsten diselenide (WSe2) field-effect transistors (FETs) synthesized using the
      chemical vapor transport method. Photoconductivity measurements show that these
      FETs display room temperature photo-responsivities of ~7 mAW-1 when illuminated
      with a laser of wavelength lambda = 658 nm with a power of 38 nW. The photo
      responsivities of these FETs showed orders of magnitude improvement (up to ~1.1
      AW-1 with external quantum efficiencies reaching as high as ~188%) upon
      application of a gate voltage (V G = -60 V). A temperature dependent (100 K < T <
      300 K) photoconductivity study reveals a weak temperature dependence of
      responsivity for these WSe2 phototransistors. We demonstrate that it is possible
      to obtain stable photo-responsivities of ~0.76 +/- 0.2 AW-1 (with applied V G = 
      60 V), at low temperatures in these FETs. These findings indicate the possibility
      of developing WSe2-based FETs for highly robust, efficient, and swift
      photodetectors with a potential for optoelectronic applications over a broad
      range of temperatures.

PMID- 30203783
TI  - Proton radiography with a commercial range telescope detector using dedicated
      post processing methods.
AB  - Proton transmission imaging uses protons with high enough energy to fully
      traverse the phantom/patient and to be captured in a suitable detector placed
      behind it. The measured residual energy or residual range provide a direct
      estimate of the water equivalent thickness (WET) of the image volume.
      Requirements for proton imaging to be exploitable in clinical practice include:
      sufficient WET accuracy and integrability into the treatment room and the
      clinical workflow, as well as an acceptably low dose to the patient and a
      sufficient spatial resolution. In this work, we report on experiments performed
      at the Institut Curie-Proton therapy center in Orsay (IC-CPO), France, using a
      commercial range telescope commonly employed for quality assurance measurements.
      The purpose was to keep the experimental set-up as simple as possible and to
      achieve nonetheless high WET accuracy radiographies by developing and applying
      dedicated post processing methods. We explain these methods in detail and discuss
      their performance. We assess the WET accuracy based on two different reference
      phantoms: a CIRS electron density phantom with tissue equivalent inserts and a
      homogeneous step phantom. We find an agreement between the measured and the
      reference WET values of 0.2-0.5 mm. The lowest investigated dose was 10 mGy per
      acquisition. It could be lowered by modifying the irradiation plan and lowering
      the beam current, though the latter would impose slight optimisations of the
      detector hardware. Our work suggests that proton radiographies with good WET
      accuracy can be obtained with a reasonable experimental effort that would
      facilitate integration into clinical routine.

PMID- 30203784
TI  - Corrections to the magnetoresistance formula for semimetals with Dirac electrons:
      the Boltzmann equation approach validated by the Kubo formula.
AB  - The magnetoresistance (MR) in semimetals with Dirac (or Weyl) electrons and free
      holes is investigated on the basis of the Boltzmann theory. The MR is modified
      from the conventional results with free electrons and holes in a very complex way
      due to the correction of the Dirac dispersion. The obtained formula explicitly
      includes the magnetic field dependence, which is very useful for the analysis of
      experimental results. In order to verify the validity of our results, the results
      obtained by the Boltzmann approach are compared with those by the Kubo theory. It
      is revealed that, by taking into account the field dependence of carrier density,
      the MR obtained by the Boltzmann theory almost perfectly agrees with that based
      on the Kubo theory even in the high-field region (in the quantum limit) except
      for the quantum oscillations. It is also shown that the MR in semimetals
      increases linearly with respect to the field in the quantum limit due to the
      drastic change of the carrier density, which is a significant characteristic of
      semimetals.

PMID- 30203785
TI  - Strain-tunable molecular doping in germanane: a first-principles study.
AB  - Germanane, fully hydrogenated germanene, has recently attracted great interest,
      both theoretical and experimental. In this paper we thoroughly study strain
      tunable n/p-type doping in germanane by adsorption of tetrathiafulvalene
      (TTF)/tetracyanoquinodimethane (TCNQ) molecules through first-principles
      calculations. The results show that both TTF and TCNQ molecules can non
      covalently functionalize the electronic properties of germanane. Not
      surprisingly, TTF molecular adsorption induces n-type doping in germanane because
      the TTF molecule is a typical electron donor. Moreover, a linearly tunable band
      gap of germanane and differing n-type doping strengths can be realized by a
      biaxial strain ranging from -3% to 3%. Analysis indicates that tensile strain
      would promote the doping effect whereas compressive strain would inhibit it.
      Comparatively, TCNQ molecular adsorption induces a germanane/TCNQ system which
      exhibits metallic characteristics. Surprisingly, however, under a tensile strain
      of 2.5%, a strong p-type doping effect is achieved in germanene/TCNQ. In
      particular, with increasing tensile strain over the range 2.5%-3%, the strain
      tunable p-type doping effect decreases gradually. Such a multiple effect of
      molecular adsorption and strain on the electronic properties of germanane could
      be helpful for potential future applications of germanane-based electron devices.

PMID- 30203786
TI  - Applications of Proteomics in Traumatic Brain Injury: Current Status and
      Potential Prospects.

PMID- 30203787
TI  - Repetitive Nerve Stimulation in Amyotrophic Lateral Sclerosis.
AB  - Background: Nowadays, it is widely known that decremental responses in low
      frequency repetitive nerve stimulation (LF-RNS) are frequently observed in
      patients with amyotrophic lateral sclerosis (ALS). The pathological mechanism of
      this phenomenon remains unknown. This study aimed to illuminate the features of
      RNS in Chinese patients with ALS. Methods: Clinical and electrophysiological data
      of 146 probable and definite ALS patients who underwent RNS were retrospectively
      enrolled and analyzed. LF-RNS (3 Hz) was performed in trapezius, deltoid,
      abductor digiti minimi (ADM), quadriceps femoris, and tibialis anterior. High
      frequency RNS (HF-RNS, 10 Hz) was performed only in ADM. The two-sample t-test
      and Chi-squared test were used for statistical analysis. Results: Decremental
      responses to LF-RNS (>=10%) in at least one muscle were detected in 83 (56.8%) of
      the cases and were most commonly seen in trapezius and deltoid. The incidence of
      decremental response was higher in patients with upper limb onset. Incremental
      responses to HF-RNS (>=60%) in ADM were observed in 6 (5.6%) of the cases. In 106
      muscles with decremental response, 62 (57.4%) muscles had a continuous
      decremental pattern, more than a U-shape pattern (37 cases, 34.3%). Nineteen
      cases showed definite decrements in LF-RNS tests in trapezius, while no
      abnormalities were found in the electromyography and neurological examination of
      the sternocleidomastoid muscle, supplied by the accessory nerve as well.
      Conclusions: Decremental responses in the RNS are commonly observed in ALS
      patients. The findings regarding the trapezius indicated that some ALS onsets
      could be initiated by a "dying back" process, with destruction of neuromuscular
      junctions (NMJs) before motor neurons. Incremental responses in the ADM implied
      damage of the NMJs involved both the post and presynaptic membranes.

PMID- 30203788
TI  - Study of Simplified Coma Scales: Acute Stroke Patients with Tracheal Intubation.
AB  - Background: Whether the Glasgow Coma Scale (GCS) can assess intubated patients is
      still a topic of controversy. We compared the test performance of the GCS motor
      component (GCS-M)/Simplified Motor Score (SMS) to the total of the GCS in
      predicting the outcomes of intubated acute severe cerebral vascular disease
      patients. Methods: A retrospective analysis of prospectively collected
      observational data was performed. Between January 2012 and October 2015, 106
      consecutive acute severe cerebral vascular disease patients with intubation were
      included in the study. GCS, GCS-M, GCS eye-opening component, and SMS were
      documented on admission and at 24, 48, and 72 h after admission to Neurointensive
      Care Unit (NCU). Outcomes were death and unfavorable prognosis (modified Rankin
      Scale: 5-6) at NCU discharge. The receiver operating characteristic (ROC) curve
      was obtained to determine the prognostic performance and best cutoff value for
      each scoring system. Comparison of the area under the ROC curves (AUCs) was
      performed using the Z- test. Results: Of 106 patients included in the study, 41
      (38.7%) patients died, and 69 (65.1%) patients had poor prognosis when discharged
      from NCU. The four time points within 72 h of admission to the NCU were
      equivalent for each scale's predictive power, except that 0 h was the best for
      each scale in predicting outcomes of patients with right-hemisphere lesions.
      Nonsignificant difference was found between GCS-M AUCs and GCS AUCs in predicting
      death at 0 h (0.721 vs. 0.717, Z = 0.135, P = 0.893) and 72 h (0.730 vs. 0.765, Z
      = 1.887, P = 0.060), in predicting poor prognosis at 0 h (0.827 vs. 0.819, Z =
      0.395, P = 0.693), 24 h (0.771 vs. 0.760, Z = 0.944, P = 0.345), 48 h (0.732 vs.
      0.741, Z = 0.593, P = 0.590), and 72 h (0.775 vs. 0.780, Z = 0.302, P = 0.763).
      AUCs in predicting death for patients with left-hemisphere lesions ranged from
      0.700 to 0.804 for GCS-M and from 0.700 to 0.824 for GCS, in predicting poor
      prognosis ranged from 0.841 to 0.969 for GCS-M and from 0.875 to 0.969 for GCS,
      with no significant difference between GCS-M AUCs and GCS AUCs within 72 h (P >
      0.05). No significant difference between GCS-M AUCs and GCS AUCs was found in
      predicting death (0.964 vs. 0.964, P = 1.000) and poor prognosis (1.000 vs.
      1.000, P = 1.000) for patients with right-hemisphere lesions at 0 h. AUCs in
      predicting death for patients with brainstem or cerebella were poor for GCS-M
      (<0.700), in predicting poor prognosis ranged from 0.727 to 0.801 for GCS-M and
      from 0.704 to 0.820 for GCS, with no significant difference between GCS-M AUCs
      and GCS AUCs within 72 h (P > 0.05). The SMS AUCs (<0.700) in predicting outcomes
      were poor. Conclusions: The GCS-M approaches the same test performance as the GCS
      in assessing the prognosis of intubated acute severe cerebral vascular disease
      patients. The GCS-M could be accurately and reliably applied in patients with
      hemisphere lesions, but caution must be taken for patients with brainstem or
      cerebella lesions.

PMID- 30203789
TI  - Volume Gain of Brainstem on Medication-Overuse Headache Using Voxel-Based
      Morphometry.
AB  - Background: Histopathology identified the anatomical and molecular abnormalities
      of brainstem nuclei in migraine patients. However, the exact whole brainstem
      structural changes in vivo have not yet been identified in medication-overuse
      headache (MOH) transformed from migraine. The aim of this study was to
      investigate the regional volume changes over the whole brainstem in the MOH
      patients using voxel-based morphometry (VBM) in vivo. Methods: High-resolution
      three-dimensional structural images were obtained using a 3.0-Tesla magnetic
      resonance system from 36 MOH patients and 32 normal controls (NCs) who were
      consecutively recruited from the International Headache Center, Chinese People's
      Liberation Army General Hospital, from March 2013 to June 2016. VBM was used to
      assess the brainstem structural alteration in the MOH patients, and voxel-wise
      correlation was performed to evaluate the relationship with the clinical
      characteristics. Results: The brainstem region with increased volume located in
      the left ventrolateral periaqueductal gray (MNI coordinate: -1, -33, -8), ventral
      tegmental area (MNI coordinate: 0, -22, -12), bilateral substantia nigra (MNI
      coordinate: -8, -16, -12, 9, -16, -12), and trigeminal root entry zone (MNI
      coordinate: -19, -29, -31; 19, -32, -29) in MOH patients compared with NCs. The
      headache visual analog scale score was positively related with the left rostral
      ventromedial medulla (RVM) (MNI coordinate: -1, -37, -56; cluster size: 20; r =
      0.602) in the MOH patients. Conclusions: The regional volume gain of brainstem
      could underlie the neuromechanism of impaired ascending and descending pathway in
      the MOH patients, and the left RVM volume alteration could imply the impaired
      tolerance of nociceptive pain input and could be used to assess the headache
      disability in the MOH patients.

PMID- 30203790
TI  - A "Triple Trouble" Case of Facioscapulohumeral Muscular Dystrophy Accompanied by
      Peripheral Neuropathy and Myoclonic Epilepsy.
AB  - Background: Facioscapulohumeral muscular dystrophy (FSHD) is characterized by
      asymmetric muscular deficit of facial, shoulder-girdle muscles, and descending to
      lower limb muscles, but it exists in several extramuscular manifestations or
      overlapping syndromes. Herein, we report a "complex disease plus" patient with
      FSHD1, accompanied by peripheral neuropathy and myoclonic epilepsy. Methods:
      Standard clinical assessments, particular auxiliary examination, histological
      analysis, and molecular analysis were performed through the new Comprehensive
      Clinical Evaluation Form, pulsed-field gel electrophoresis-based Southern blot,
      Multiplex Ligation-dependent Probe Amplification (MLPA), whole exome sequencing
      (WES), and targeted methylation sequencing. Results: The patient presented with
      mild facial weakness, humeral poly-hill sign, scapular winging, peroneal
      weakness, drop foot, pes cavus, and myoclonic epilepsy. Furthermore,
      electrophysiology revealed severely demyelinated and axonal injury. The muscle
      and nerve biopsy revealed broadly fiber Type II grouping atrophy and myelinated
      nerve fibers that significantly decreased with thin myelinated fibers and onion
      bulbs changes. Generalized sharp and sharp-slow wave complexes on
      electroencephalography support the diagnosis toward myoclonic epilepsy. In
      addition, molecular testing demonstrated a co-segregated 20-kb 4q35-EcoRI
      fragment and permissive allele A, which corresponded with D4Z4 hypomethylation
      status in the family. Both the patient's mother and brother only presented the
      typical FSHD but lacked overlapping syndromes. However, no mutations for
      hereditary peripheral neuropathy and myoclonic epilepsy were discovered by MLPA
      and WES. Conclusions: The present study described a "tripe trouble" with FSHD,
      peripheral neuropathy, and myoclonic epilepsy, adding the spectrum of overlapping
      syndromes and contributing to the credible diagnosis of atypical phenotype. It
      would provide a direct clue on medical care and genetic counseling.

PMID- 30203791
TI  - Combined Effects of Electroacupuncture and Behavioral Training on Learning-Memory
      Ability and Event-Related Potential P300 in Rats with Mid/Advanced Cerebral
      Infarction.
AB  - Background: The effectiveness of the combination of electroacupuncture (EA) and
      behavioral training (BT) for mid/advanced cerebral infarction (M/ACI) and related
      mechanisms remains unclear. This study aimed to investigate the combined effects
      on the learning-memory ability and event-related potential P300 in rats with
      M/ACI. Methods: Eighty rats with M/ACI were divided into Group Model (M), Group
      EA, Group BT, and Group EA-BT (n = 20) according to the random number with five
      healthy rats in Group Control (CON). On the 6th week after modeling, EA, BT, and
      EA-BT were given to Group EA, Group BT, and Group EA-BT, respectively, whereas
      Group M and Group CON were not given any intervention. Y-maze test and P300 were
      recorded before and after the intervention. Results: After intervention, the P300
      latency was lower and the amplitude was higher in the Group EA-BT, Group EA, and
      Group BT than before (for latency, t = -7.638, -4.334, and -5.916; for amplitude,
      t = 8.125, 3.846, and 5.238; P < 0.01), with Group EA-BT superior to Group EA
      (for latency, t = -3.708; for amplitude, t = 3.653; P < 0.01) and Group BT (for
      latency, t = -2.067; for amplitude, t = 2.816; P < 0.05), with no significant
      difference between Group BT and EA (for latency, t = -1.439; for amplitude, t =
      1.075; P > 0.05). While the performances of Y-maze tests in the Group EA-BT,
      Group EA, and Group BT were all better than before (t = 10.359, 4.520, and 7.791,
      P < 0.01), with Group EA-BT better than Group EA (t = 5.627, P < 0.01) and Group
      BT (t = 2.913, P < 0.01) respectively, and Group BT better than Group EA (t =
      2.912, P < 0.01). Conclusion: EA or BT can affect P300 in rats with M/ACI, and
      the combination of these two methods can significantly improve the learning
      memory ability.

PMID- 30203792
TI  - Total Arterial Off-Pump Coronary Artery Bypass Grafting: A 10-Year Experience.
AB  - Background: Arterial grafts had better mid-term and long-term patency than
      saphenous vein grafts in coronary artery bypass grafting (CABG). We summarized
      our experience with total arterial off-pump coronary artery bypass grafting
      (OPCAB) and assessed the early clinical results, surgical complications, and
      follow-up. Methods: From January 2007 to May 2017, 508 coronary artery disease
      patients undergoing total arterial OPCAB were enrolled. Clinical features,
      approaches, outcomes of surgical treatments, and follow-up data of these patients
      were studied retrospectively. A total of 122 patients underwent single left
      internal mammary artery (IMA)-left anterior descending artery grafts, whereas the
      other 386 patients underwent multiple vessel grafts. Results: The average distal
      anastomosis was 2.34 +/- 0.97 (range: 1-4). All the patients were discharged from
      hospital except one died. A total of 457 (90.32%) patients were followed up. In
      the 4-, 7-, and 10-year follow-up groups, the rate of death from any cause was
      1.19%, 6.47%, and 10.67%; rate of cardiac death was 0.60%, 2.88%, and 3.33%; rate
      of repeat revascularization was 0.00%, 3.60%, and 8.67%; rate of ischemic
      symptoms was 1.79%, 7.91%, and 11.33%; and incidence of stroke was 2.38%, 4.32%,
      and 6.67%, respectively. Poor medication adherence was observed in 9.38% of the
      follow-up population. Conclusions: Total arterial OPCAB with bilateral IMA,
      radial artery, and right gastroepiploic artery grafting yielded satisfactory
      early and midterm outcomes in this patient group, without a significant increase
      in early mortality or morbidity. Moreover, the long-term outcomes are also
      positive.

PMID- 30203793
TI  - Relationship of Cell Compositions in Allografts with Outcomes after
      Haploidentical Transplantation for Acquired Severe Aplastic Anemia: Effects of
      CD34+ and CD14+ Cell Doses.
AB  - Background: The dose of certain cell types in allografts affects engraftment
      kinetics and clinical outcomes after allogeneic stem cell transplantation (SCT).
      Hence, the present study investigated the association of cell compositions in
      allografts with outcomes after unmanipulated haploidentical SCT (haplo-SCT) for
      patients with acquired severe aplastic anemia (SAA). Methods: A total of 131
      patients with SAA who underwent haplo-SCT were retrospectively enrolled. Cell
      subsets in allografts were determined using flow cytometry. To analyze the
      association of cellular compositions and outcomes, Mann-Whitney U nonparametric
      tests were conducted for patient age, sex, weight, human leukocyte antigen
      mismatched loci, ABO-matched status, patient ABO blood type, donor-recipient sex
      match, donor-recipient relationship, and each graft component. Multivariate
      analysis was performed using logistic regression to determine independent
      influence factors involving dichotomous variables selected from the univariate
      analysis. Results: A total of 126 patients (97.7%) achieved neutrophil
      engraftment, and 121 patients (95.7%) achieved platelet engraftment. At 100 days
      after transplantation, the cumulative incidence of II-IV acute graft-versus-host
      disease (GVHD) was 32.6%. After a median follow-up of 842 (range: 124-4110) days
      for surviving patients, the cumulative incidence of total chronic GVHD at 3 years
      after transplantation was 33.7%. The probability of overall survival at 3 years
      was 83.0%. Multivariate analysis showed that higher total doses of CD14+ (P =
      0.018) and CD34+ cells (P < 0.001) were associated with a successful platelet
      engraftment. A successful platelet was associated with superior survival (P <
      0.001). No correlation of other cell components with outcomes was observed.
      Conclusions: These results provide evidence and explain that higher doses of
      CD34+ and CD14+ cells in haploidentical allografts positively affect platelet
      engraftment, contributing to superior survival for patients with SAA.

PMID- 30203794
TI  - MicroRNA Dysregulation and Steroid Hormone Receptor Expression in Uterine Tissues
      of Rats with Endometriosis during the Implantation Window.
AB  - Background: Estrogen receptor (ER) and progesterone receptor (PR) are involved in
      endometriosis, but the involvement of microRNAs (miRNAs) is unknown. The aim of
      the study was to explore the correlation between miRNA and ER/PR in uterine
      tissues of rats with endometriosis during the implantation window. Methods:
      Twenty female Sprague-Dawley rats were randomized in three groups: endometriosis
      (n = 7), fat tissue control (n = 6), and normal (n = 7) groups. The female rats
      were mated and sacrificed on day 5 (implantation). Uterine tissues were obtained
      for hematoxylin-eosin staining, immunohistochemistry, and miRNA expression.
      Reverse transcription polymerase chain reaction (RT-PCR) was used to validate the
      expression of rno-miR-29c-3p, rno-miR-34c-5p, rno-miR-141-5p, rno-miR-24-1-5p,
      and rno-miR-490-5p. Results: The 475 miRNAs were found to differentially express
      between the endometriosis and normal control groups, with 127 being upregulated
      and 348 being downregulated. Expression of five miRNAs (rno-miR-29c-3p, rno-miR
      34c-5p, rno-miR-141-5p, rno-miR-24-1-5p, and rno-miR-490-5p) were validated by RT
      PCR and found to be differentially expressed among the three groups. Expression
      of ER and PR proteins (immunohistochemistry) in the glandular epithelium and
      endometrial stroma was significantly different among the three groups (all P <
      0.05). Five miRNAs were involved in pathways probably taking part in implantation
      and fertility. Conclusions: The results suggested that miRNAs, ER, and PR could
      play important roles in the embryo implantation period of rats with
      endometriosis. These miRNAs might play a role in endometrial receptivity in
      endometriosis.

PMID- 30203795
TI  - A Rare Missense Variant in Telomerase Reverse Transcriptase is Associated with
      Idiopathic Pulmonary Fibrosis in a Chinese Han Family.
AB  - Background: Idiopathic pulmonary fibrosis (IPF) is an age-related and progressive
      interstitial lung disease. Up to 20% of cases of IPF cluster in families, genetic
      factors contribute significantly to the pathogenesis of the disease. This study
      aimed to explore the association between rare genetic variants and IPF in Chinese
      Han families. Methods: A Han family, comprising three IPF patients and five
      unaffected their first-degree relatives, and 100 ethnically matched control
      individuals from North China were enrolled in this study. Peripheral blood was
      collected, and genomic DNA was extracted. To elucidate if rare genetic variants
      are associated with the familial IPF, we performed whole-exome sequencing of
      affected members from a Chinese Han IPF family. Candidate rare variants were then
      confirmed by Sanger sequencing. Results: We identified a potentially damaging
      rare variant-a heterozygous mutation c.2146G>A in exon 6 of the gene encoding for
      telomerase reverse transcriptase (TERT), which results in an amino acid
      substitution (p.Ala716Thr). We confirmed the missense mutation by Sanger
      sequencing in all the affected family members but did not detect this mutation in
      100 ethnically matched healthy controls. Patients carried this mutation were
      characterized by the frequently acute exacerbation of IPF phenotype, with poor
      prognosis. The mean time to death was 2.8 years after diagnosis. Conclusion:
      Using next-generation sequencing technology in familial IPF patients, we
      identified the heterozygous rare variant in TERT gene, and strengthened the
      importance of genetic variants in telomere-related pathogenesis in Chinese IPF
      patients.

PMID- 30203798
TI  - Effect of Human Umbilical Vein Endothelial Cells on Immune Responses of
      Lipopolysaccharide-Induced THP1 Macrophages.

PMID- 30203796
TI  - Extent of Lung Involvement and Serum Cryptococcal Antigen Test in Non-Human
      Immunodeficiency Virus Adult Patients with Pulmonary Cryptococcosis.
AB  - Background: Serum cryptococcal antigen (CrAg) test is the most used noninvasive
      method to detect cryptococcal infection. However, false-negative CrAg test is not
      uncommon in clinical practice. Then, the aim of this study was to investigate the
      factors associated with false-negative CrAg test among non-human immunodeficiency
      virus (HIV) adult patients with pulmonary cryptococcosis and its clinical
      features. Methods: One hundred and fourteen non-HIV adult patients with pulmonary
      cryptococcosis, proven by biopsy, were retrospectively reviewed. Finally, 85
      patients were enrolled; 56 were CrAg positive (CrAg+ group) and 29 were negative
      (CrAg- group). It was a cross-sectional study. Then, baseline characteristics,
      underlying diseases, clinical symptoms, laboratory findings, and chest
      radiological findings were reviewed and analyzed. Chi-square test was used to
      analyze categorical variable. Odds ratio (OR) was used to measure correlation.
      Student's t- test was obtained to analyze continuous variable. Results: No
      difference in baseline characteristics, underlying diseases, clinical symptoms,
      and laboratory findings were found between two groups (P > 0.05 in all).
      Nevertheless, diffuse extent lesion was 82.1% in CrAg+ group and 10.3% in CrAg-
      group (chi2 = 40.34, P < 0.001; OR = 39.87). Conclusions: Among patients with
      limited pulmonary involvement, a negative serum CrAg does not preclude the
      diagnosis of pulmonary cryptococcosis. However, among patients with extensive
      pulmonary involvement, serum CrAg is a useful diagnostic tool for pulmonary
      cryptococcosis. Furthermore, we also noticed that the untypical and mild
      presentations with extensive pulmonary lesion might be the features of pulmonary
      cryptococcosis, which needs further investigation.

PMID- 30203799
TI  - Effect of Mechanical Stress in Combination with Verapamil on Levels of Aggrecan
      and ADAMTS-5 mRNAs and Proteins in Human Osteoarthritic Chondrocyte/Agarose
      Constructs.

PMID- 30203797
TI  - Effect of Regulatory Network of Exosomes and microRNAs on Neurodegenerative
      Diseases.
AB  - Objective: A comprehensive review of the network regulation of exosomes and
      microRNAs (miRNAs) in neurodegenerative diseases was done, centering on the
      mechanism of the formation of exosomes and miRNAs and the sorting mechanism of
      exosomal miRNAs, with the aim to provide a theoretical basis in the search of
      biomarkers and the treatment of neurodegenerative diseases. Data Sources: The
      comprehensive search used online literature databases including NCBI PubMed, Web
      of Science, Google Scholar, and Baidu Scholar. Study Selection: The study
      selection was based on the following keywords: exosomes, miRNAs, central nervous
      system (CNS), and neurodegenerative diseases. The time limit for literature
      retrieval was from the year 2000 to 2018, with language restriction in English.
      Relevant articles were carefully reviewed, with no exclusions applied to study
      design and publication type. Results: Exosomes are the smallest nanoscale
      membranous microvesicles secreted by cells and contain important miRNAs, among
      other rich contents. In the CNS, exosomes can transport amyloid beta-protein,
      alpha-synuclein, Huntington-associated protein 1, and superoxide dismutase I to
      other cells. These events relieve the abnormal accumulation of proteins and
      aggravating neurological diseases. In some neurodegenerative diseases including
      Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic
      lateral sclerosis, miRNAs are pathologically altered as an inexorable course,
      suggesting that miRNAs may contribute neurodegeneration. Exosomes and miRNAs form
      a network to regulate the homeostasis of the CNS, both synergistically and
      individually. Conclusion: The network of exosomes and miRNAs that regulates CNS
      homeostasis is a promising biomarker for the diagnosis and treatment of
      neurodegenerative diseases.

PMID- 30203801
TI  - Monochorionic Triplet Gestation after in Vitro Fertilization.

PMID- 30203800
TI  - Intracerebral Hemorrhage and Venous Infarction after Deep Brain Stimulation Lead
      Placement.

PMID- 30203802
TI  - Reversible Cerebral Vasoconstriction Syndrome following Guillain-Barre Syndrome:
      A Rare Complication.

PMID- 30203804
TI  - Length-Heterogeneity Polymerase Chain Reaction as a Diagnostic Tool for Bacterial
      Vaginosis.

PMID- 30203803
TI  - Low-density Lipoprotein Cholesterol/High-density Lipoprotein Cholesterol Ratio as
      Predictor of First Acute Myocardial Infarction and Major Adverse Cardiovascular
      Event after Intervention in Young Males.

PMID- 30203805
TI  - Gastrointestinal Stromal Tumors with KIT Mutation Coexisting with Wild-type
      Gastrointestinal Stromal Tumors in a Patient with Neurofibromatosis Type 1.

PMID- 30203806
TI  - Multimodal Magnetic Resonance Imaging Studies of Migraines Related to Increasing
      Risk Factors for Brain Lesions Would Be an Optimal Research Focus: A Pilot
      Literature Citation Analysis.

PMID- 30203807
TI  - Coronary Artery Aneurysm Formation after Drug-Coated Balloon Treatment.

PMID- 30203808
TI  - Detection Capability of the Stool Helicobacter pylori Antigen Kit Using Gastric
      Juice Collected during Esophagogastroduodenoscopy.

PMID- 30203809
TI  - Case Reports of a Giant Cell Reparative Granuloma and a Giant Cell Tumor on
      Temporal Bone.

PMID- 30203810
TI  - New Dimensional Perspectives on Differential Diagnosis of Pleural Effusion.

PMID- 30203811
TI  - Inflammatory Myofibroblastic Tumor of Urinary Bladder.

PMID- 30203812
TI  - Successful Adaptation of Targeted Gene Panel Next-Generation Sequencing in
      Regional Hospital in Hong Kong: Genomic Diagnosis of SCN2A-Related Seizure
      Disorder.

PMID- 30203813
TI  - Development of Medical Lasers for Treatment on Benign Prostatic Hyperplasia.

PMID- 30203814
TI  - Corrigendum: Bone Metabolic Markers in Patients with Obstructive Sleep Apnea
      Syndrome.
AB  - [This corrects the article DOI: 10.4103/0366-6999.238149].

PMID- 30203816
TI  - Efficient and reliable surface charge transfer doping of black phosphorus via
      atomic layer deposited MgO toward high performance complementary circuits.
AB  - Black phosphorus (BP), a fast emerging 2D material, has shown great potential in
      future electronics and optoelectronics owing to its outstanding properties
      including sizable band gap and ambipolar transport characteristics. However, its
      hole conduction dominance, featured by a much larger hole mobility and the
      corresponding on-current than that of the electrons, renders the reliable
      modulation of its carrier type and density a key challenge, thereby hindering its
      application to complementary electronics. Here, we demonstrate an efficient and
      reliable n-type doping for BP transistors via surface functionalization by atomic
      layer deposited magnesium oxide (MgO) with favorable controllability. By
      optimizing the MgO thickness, an electron mobility of up to 95.5 cm2 V-1 s-1 is
      reached with a simultaneous significant suppression of hole conduction.
      Subsequently, a high-performance complementary logic inverter is demonstrated
      within a single BP flake, which operates well with a supply voltage as low as
      <0.5 V, outperforming reported BP inverters in terms of logic level match, power
      consumption and process feasibility. Our findings suggest that surface charge
      transfer doping via MgO can be used as a promising technique towards high
      performance BP-based functional nanoelectronics.

PMID- 30203815
TI  - Rs12976445 Polymorphism Is Associated with Post-Ablation Recurrence of Atrial
      Fibrillation by Modulating the Expression of MicroRNA-125a and Interleukin-6R.
AB  - BACKGROUND This study aimed to identify the relationship between miR-125a
      polymorphism rs12976445 and the post-ablation recurrence of atrial fibrillation
      (AF), as well as to explore the underlying mechanism of miR-125a in AF
      recurrence. MATERIAL AND METHODS Microarray analysis was performed to search for
      miRNAs potentially involved in the regulation of AF recurrence, while real-time
      PCR (polymerase chain reaction) and Western blot analyses were carried out to
      study the expression of miR-125a (microRNA-125a), IL-6R (interleukin-6 receptor),
      and IL-16 (interleukin-16) in different experimental groups, so as to understand
      the regulatory relationships among miR-125a, IL-6R, and IL-16. Subsequently, a
      logistic regression analysis was utilized to investigate the survival status of
      recurrent AF in subjects harboring different genotypes of rs12976445. RESULTS The
      subjects in the GG and GC/CC groups of miR-125a polymorphism rs12976445 showed no
      obvious difference regarding all demographic characteristics that were collected
      in this study. In addition, 19 miRNAs were identified as potentially involved in
      the regulation of AF recurrence. Among these miRNAs, 6 were upregulated and 13
      were downregulated in the group with early recurrence. According to real-time PCR
      results, the expression of miR-125a was dramatically upregulated in LRAF (late
      recurrence of atrial fibrillation) as well as in subjects harboring the GG
      genotype. On the contrary, the level of IL-6R mRNA was dramatically downregulated
      in LRAF and subjects harboring the GG genotype. Furthermore, IL-6R was confirmed
      as a candidate target of miR-125a by a luciferase reporter assay. CONCLUSIONS
      MicroRNA-125a polymorphism rs12976445 plays a role in AF recurrence via the
      regulation of IL-6R.

PMID- 30203817
TI  - A surface transition of nanoparticle-decorated graphene films from water-adhesive
      to water-repellent.
AB  - Herein, a facile strategy is introduced to realize the transition of graphene
      films from a water-adhesion surface (adhesive pressure of 541.5 Pa) to a water
      repellent surface (adhesive pressure of ~0 Pa) via decoration of carbon
      nanoparticles. Cassie impregnating wetting state and Cassie state are used to
      explain highly adhesive effect and strong repelling effect, respectively. Droplet
      impacting experiments demonstrate that the as-prepared graphene films have a
      stable structure, which is beneficial for their applications.

PMID- 30203818
TI  - Mitochondria-targeting single-layered graphene quantum dots with dual recognition
      sites for ATP imaging in living cells.
AB  - As a molecular unit of intracellular energy transfer, adenosine triphosphate
      (ATP) is significant for maintaining the energy balance in living cells and thus
      monitoring cellular ATP is important to assess cellular physiological functions.
      However, effective monitoring of cellular ATP still faces challenges owing to the
      similarity of ATP to other nucleoside polyphosphates. Herein, yellow emissive
      single-layered graphene quantum dots (s-GQDs) with dual recognition sites
      including pi-conjugated single sheets and positively charged sites were
      developed. The s-GQDs exhibit a good mitochondria targeting ability and respond
      only to purine nucleotides and show good selectivity in discriminating tri-, di-
      and monophosphate nucleotides. The good selectivity should be attributed to the
      concurrent effect of pi-pi stacking and electrostatic interactions between filmy
      layered positive s-GQDs and negative purine nucleotides. Owing to the
      mitochondria targeting ability and dual recognition sites of the s-GQDs, the
      mitochondrial ATP fluctuation resulting from the activation and suppression of
      ATP in living cells has been successfully monitored.

PMID- 30203819
TI  - Nano-arrayed OLEDs: enhanced outcoupling efficiency and suppressed efficiency
      roll-off.
AB  - Organic light-emitting diodes (OLEDs) with an enhanced outcoupling efficiency and
      a suppressed efficiency roll-off were fabricated by inserting a nanosize pixel
      defining layer (nPDL) that defines the OLED emission region as an array of
      nanoholes. The outcoupling efficiency of the nano-arrayed OLEDs was increased
      through the reduced surface plasmon polariton loss caused by the wavy diffraction
      grating at the metal-organic interface, and their efficiency roll-off was
      suppressed through the diffusive exciton outside the exciton-formation zone. As a
      result, the nano-arrayed OLEDs exhibited enhancements of 148.7% in the power
      efficiency and 137.0% in the external quantum efficiency at 1000 cd m-2 compared
      with a reference device. Furthermore, the critical current density (J0) where the
      external quantum efficiency decreased to half of its initial value was improved
      by a factor of 2.5.

PMID- 30203820
TI  - Azodicarboxylate-free esterification with triphenylphosphine mediated by flavin
      and visible light: method development and stereoselectivity control.
AB  - Triphenylphosphine (Ph3P) activated by various electrophiles (e.g., alkyl
      diazocarboxylates) represents an effective mediator of esterification and other
      nucleophilic substitution reactions. We report herein an aza-reagent-free
      procedure using flavin catalyst (3-methyl riboflavin tetraacetate),
      triphenylphosphine, and visible light (448 nm), which allows effective
      esterification of aromatic and aliphatic carboxylic acids with alcohols.
      Mechanistic study confirmed that photoinduced electron transfer from
      triphenylphosphine to excited flavin with the formation of Ph3P+ is a crucial
      step in the catalytic cycle. This allows reactive alkoxyphosphonium species to be
      generated by reaction of an alcohol with Ph3P+ followed by single-electron
      oxidation. Unexpected stereoselectivity control by the solvent was observed,
      allowing switching from inversion to retention of configuration during
      esterification of (S)- or (R)-1-phenylethanol; for example with phenylacetic
      acid, the ratio shifting from 10 : 90 (retention : inversion) in
      trifluoromethylbenzene to 99.9 : 0.1 in acetonitrile. Our method uses
      nitrobenzene to regenerate the flavin photocatalyst. This new approach to flavin
      re-oxidation has also been successfully proved in benzyl alcohol oxidation, which
      is a "standard" process among flavin-mediated photooxidations.

PMID- 30203821
TI  - Androsterone-based gels enable diastereospecific reductions and
      diastereoselective epoxidations of gelators.
AB  - Eleven new androsterone-based gelators were synthesized, and their gelation
      properties and gel-mediated reactions were investigated. The relationships
      between the structures, gelation and self-assembly processes of the gelators are
      discussed. By using granular PTFE (polytetrafluoroethylene) as costirrers,
      quantitative and diastereospecific reductions of the gelator carbonyl groups
      mediated by water were achieved in the gels of seven gelators. This reduction did
      not occur in the control experiment which used organic solvent-mediated
      conventional conditions. The diastereospecific and quantitative reductions
      possibly occur via a hydrogen-bonded-activated carbonyl mechanism. Five of the
      gelators underwent gel-mediated epoxidation and the products were more
      diastereoselective than those obtained using conventional epoxidation reactions.
      This can be attributed to the ordered arrangements in the gels.

PMID- 30203822
TI  - Probing hydrogen bonding interactions and impurity intercalation in gibbsite
      using experimental and theoretical XANES spectroscopy.
AB  - The Al and O K-edge XANES spectra of Bayer process gibbsite are examined, both
      experimentally and with plane wave density functional theory, and transition
      assignments are made. We confirm that the broad transitions in Al K-edge spectra
      are fundamentally the same as those in more ordered and well-studied corundum,
      and typical of octahedrally coordinated aluminium. Analysis of O K-edge spectra
      reveals that while much of the initial edge transition structure (535-548 eV) is
      due to O 2p hybridization with Al orbitals, the lowest energy region (~535-539
      eV) is particularly influenced by O-H states which are heavily perturbed by
      hydrogen bonding interactions. We therefore tentatively suggest that an
      unexplained structure at 539 eV in O K-edge spectra of corundum may be due to
      surface hydroxylation. Finally, we examined Na K-edge spectra, as sodium is the
      major impurity in these materials and implicated in perturbation of the evolution
      of materials properties with calcination through the transition aluminas. Density
      functional theory calculations find sodium replacement of in-sheet H-atoms is the
      most thermodynamically stable site for sodium inclusion. We subsequently confirm
      this assignment spectroscopically, explicitly demonstrating the precise location
      of Na+ impurities for the first time.

PMID- 30203823
TI  - Human-based fibrillar nanocomposite hydrogels as bioinstructive matrices to tune
      stem cell behavior.
AB  - The extracellular matrix (ECM)-biomimetic fibrillar structure of platelet lysate
      (PL) gels along with their enriched milieu of biomolecules has drawn significant
      interest in regenerative medicine applications. However, PL-based gels have poor
      structural stability, which severely limits their performance as a bioinstructive
      biomaterial. Here, rod-shaped cellulose nanocrystals (CNC) are used as a novel
      approach to modulate the physical and biochemical microenvironment of PL gels
      enabling their effective use as injectable human-based cell scaffolds with a
      level of biomimicry that is difficult to recreate with synthetic biomaterials.
      The incorporation of CNC (0 to 0.61 wt%) into the PL fibrillar network during the
      coagulation cascade leads to decreased fiber branching, increased interfiber
      porosity (from 66 to 83%) and modulates fiber (from 1.4 +/- 0.7 to 27 +/- 12 kPa)
      and bulk hydrogel (from 18 +/- 4 to 1256 +/- 82 Pa) mechanical properties. As a
      result of these physicochemical alterations, nanocomposite PL hydrogels resist
      the typical extensive clot retraction (from 76 +/- 1 to 24 +/- 3 at day 7) and
      show favored retention of PL bioactive molecules. The feedback of these cues on
      the fate of human adipose-derived stem cells is evaluated, showing how it can be
      explored to modulate the commitment of encapsulated stem cells toward different
      genetic phenotypes without the need for additional external biological stimuli.
      These fibrillar nanocomposite hydrogels allow therefore the exploration of the
      outstanding biological properties of human-based PL as an efficient engineered
      ECM which can be tailored to trigger specific regenerative pathways in minimal
      invasive strategies.

PMID- 30203824
TI  - Ultrafine Mo-doped SnO2 nanostructure and derivative Mo-doped Sn/C nanofibers for
      high-performance lithium-ion batteries.
AB  - Tin-based materials have been intensively studied as attractive candidates for
      high-capacity and long-cycle-life anodes in Li-ion batteries (LIBs) owing to
      their low cost and high energy density. However, they all suffer from severe
      structural decay during the lithium ion insertion/extraction process, which
      results in deterioration in the overall performance of the batteries. To mitigate
      this problem, we have synthesized a Mo-doped SnO2 nanostructure via a facile
      hydrothermal method, which then fragmented into ultrafine particles after dozens
      of cycles. The fracture-resistant size and ample contact with Super-P and Li2O
      greatly improved the electrochemical kinetics and cyclability to deliver a
      reversible capacity of 670 mA h g-1 after 700 cycles, which demonstrated the
      potential suitability of Mo-doped SnO2 nanoparticles as a long-cycle-life anode
      material. Then, the compounds were uniformly dispersed in carbon nanofibers and
      reduced in situ to prepare a free-standing anode via electrospinning and
      carbonization. When used directly as an anode in LIBs (without a polymeric binder
      or conductive agent, as well as a current collector), the nanofiber membrane
      anode delivered comparable cycling performance and capacity to that of a slurry
      coated electrode.

PMID- 30203825
TI  - Investigation of nematic to smectic phase transition and dynamical properties of
      strongly confined semiflexible polymers using Langevin dynamics.
AB  - We investigated the nematic to smectic phase transition for strongly confined
      semiflexible polymer solutions in slit-like confinements using GPU-accelerated
      Langevin dynamics. We characterized the phase transitions from the nematic to
      smectic phases for semi-flexible polymer solutions as the polymer density
      increased. The dependence for the lyotropic nematic to smectic transition can be
      collapsed by scaling exponents between 0.2 and 0.3. The smectic C phase is found
      for all the cases with the polymer orientation director tilted with respect to
      smectic layer lateral alignment. As the chain rigidity increases, the transition
      density decreases for systems in which the polymer persistence length (P) to slit
      height (H) ratios are 1.25, 2.5, 3.75, 5 and 25. We also characterized the
      polymer dynamics for the isotropic-nematic-smectic transitions. The overall
      polymer diffusivity decreased steadily as the polymer density increased. We
      observed anomalous polymer diffusion along the nematic director near the
      isotropic-nematic transition, similar to previously reported behavior for nematic
      forming ellipsoids. Polymer diffusivity decreased sharply by two orders of
      magnitude upon the nematic-smectic transition.

PMID- 30203826
TI  - Cavitation in inhomogeneous soft solids.
AB  - A tiny spherical cavity expands in a homogenous neo-Hookean solid when subjected
      to an externally applied hydrostatic tension. If the applied tension reaches 2.5
      times the shear modulus of the solid, the cavity expands unboundedly. Such a
      phenomenon is usually referred to as cavitation in soft solids. In previous
      studies, the soft solid is often assumed to have homogeneous mechanical
      properties. In this article, we study cavity expansion in inhomogeneous soft
      solids through analytical formulation and finite element simulations. We find
      that cavitation in an inhomogeneous soft solid can be greatly different from that
      in a homogenous one. In particular, we show that the relationship between the
      applied hydrostatic tension and the cavity size can be either monotonic or non
      monotonic, depending on the geometry and material properties of the soft solid.
      We hope the results obtained in this article will be helpful in understanding the
      cavitation phenomenon in complex soft materials.

PMID- 30203827
TI  - Magnetoelectric coupling in nanoscale 0-1 connectivity.
AB  - The strain-mediated magnetoelectric (ME) coupling between piezoelectric (PE) and
      magnetostrictive (MS) components are established in various connectivities.
      Discovering new ME connectivity and elucidating the key factors governing the
      performance of ME composite are of critical importance to find advanced materials
      for modern electronics. Reported here is a novel ME coupling in 0-1 connectivity.
      The unique self-assembling ability of 1-dimension crystalline nanocellulose (CNC)
      nanowhiskers enables the establishment of ME coupling with 0-dimension cobalt
      ferrite (CFO) nanoparticles without the use of binder. The developed CFO/CNC 0-1
      ME composites display a significant ME voltage coefficient (alphaME) as high as
      0.135 mV cm-1 Oe-1. The CFO nanoparticles are also modified with a cationic
      surfactant, cetyltrimethylammonium bromide (CTAB), to reduce their dispersion
      ability. A ME response related to the rearrangement of aggregated MS
      nanoparticles is observed in the CTAB-CFO/CNC composites, which differs from the
      typical magnetostriction induced ME effect in nanoparticulate ME composites.

PMID- 30203828
TI  - Purine-substituted imidazolium mesomeric betaines and their tautomeric N
      heterocyclic carbenes. Formation of a cyclic borane adduct.
AB  - 6-Chloropurine and 2,6-dichloropurine were reacted with N1-substituted imidazoles
      to give purin-6-yl substituted imidazolium salts, respectively. Deprotonation of
      the 1-methylimidazolium derivative resulted in the formation of the corresponding
      stable conjugated mesomeric betaine, whereas the 1-phenyl,- 1-vinyl- and 1-(2
      hydroxyethyl) derivatives proved to be unstable. In situ generation of the
      mesomeric betaines by caesium carbonate in the presence of sulfur and selenium,
      however, gave the thiones and the selenones of the tautomeric purine-substituted
      imidazol-2-ylidene, respectively. Its anionic N-heterocyclic carbene was formally
      trapped by reaction with triethylborane at high temperatures as a cyclic boron
      adduct which is the first representative of a new heterocyclic ring system. DFT
      calculations gained insight into the electronic properties of the N-heterocyclic
      carbenes substituted by pi-electron donators. Results of a single crystal X-ray
      analysis of the boron adduct are presented.

PMID- 30203829
TI  - Synthesis of disaccharide nucleoside analogues as potential poly(ADP-ribose)
      polymerase-1 inhibitors.
AB  - Poly(ADP-ribose) polymerase-1 (PARP-1) is an important target in cancer therapy.
      We present the synthesis of novel disaccharide nucleoside analogues that resemble
      the central motif of poly(ADP-ribose) and test their inhibitory effects on human
      PARP-1. Some compounds show inhibition of enzymatic activity in vitro and thus
      might be interesting for further investigations.

PMID- 30203830
TI  - C-H functionalisation of aldehydes using light generated, non-stabilised diazo
      compounds in flow.
AB  - The difficulty in accessing and safely utilising non-stabilised diazo species has
      in the past limited the application of this class of compounds. Here we explore
      further the use of oxadiazolines, non-stabilised diazo precursors which are bench
      stable, in direct, non-catalytic, aldehyde C-H functionalisation reactions under
      UV photolysis in flow and free from additives. Commercially available aldehydes
      are coupled to afford unsymmetrical aryl-alkyl and alkyl-alkyl ketones while mild
      conditions and lack of transition metal catalysts allow for exceptional
      functional group tolerance. Examples are given on small scale and in a larger
      scale continuous production.

PMID- 30203831
TI  - Thio-Michael addition of thioamides and allenes for the selective construction of
      polysubstituted 2-arylthiophenes via TBAI/H2O2 promoted tandem oxidative
      annulation and 1,2-sulfur migration.
AB  - A novel TBAI-catalyzed tandem thio-Michael addition/oxidative annulation of
      allenes and thioamides for the construction of polysubstituted 2-arylthiophenes
      under a sulfur migration transformation protocol has been developed. The
      transition-metal-free protocol achieves the oxidative cyclization reaction of
      thioamides containing electron-rich substituents with allenes to construct
      polysubstituted thiophenes selectively by controlling oxidation conditions.

PMID- 30203832
TI  - A phase 1/2, open-label, dose-escalation study of midostaurin in children with
      relapsed or refractory acute leukaemia.

PMID- 30203833
TI  - Clinical value of automated fibrin generation markers in patients with septic
      shock: a SepsiCoag ancillary study.
AB  - An ancillary analysis to the SepsiCoag multicentric prospective observational
      study on patients entering an intensive care unit with septic shock evaluated the
      prognostic potential of fibrin generation markers (FGMs) tested at inclusion in
      the study, on survival at day 30. After centralization of samples, three
      automated FGMs were compared: D-dimers (DDi), fibrin/fibrinogen degradation
      products (FDP) and fibrin monomers (FM). FM was the single FGM that was
      significantly higher in non-surviving patients, area under the receiver-operator
      characteristic curve (AUCROC ): 0.617, P < 0.0001. Significantly higher
      International Society on Thrombosis and Haemostasis Disseminated Intravascular
      Coagulation (ISTH DIC) scores were calculated in non-survivors using each of the
      three FGMs. A dose-effect relationship was observed between ISTH DIC scores and
      non-survival, with highest significance obtained using FM as the FGM. An overt
      DIC diagnosis using the ISTH DIC score calculated using FM was a predictor of non
      survival at day 30, independently from overt DIC diagnosis based on scores
      calculated using FDP or DDi. The AUCROC values testing the ability of the ISTH
      DIC score to predict non-survival were 0.650, 0.624 and 0.602 using FM, DDi and
      FDP, respectively, as the FGM. In patients with septic shock, among the
      commercially-available automated assays, automated FM is the FGM best related
      with late prognosis.

PMID- 30203834
TI  - Early-onset group B streptococcal disease in a risk factor-based prevention
      setting: A 15-year population-based study.
AB  - BACKGROUND: Intrapartum chemoprophylaxis reduces early-onset group B
      streptococcal disease (EOGBSD) in newborns. Some guidelines advise that
      intrapartum antibiotics should be offered following universal antenatal screening
      for GBS carriage and others recommend intrapartum antibiotics based on clinical
      risk factors alone. Since 1999, Queensland guidelines have recommended a risk
      factor-based approach. We examined trends in EOGBSD rates over time in Queensland
      in the setting of these guidelines and whether management of cases reflected the
      recommendations. METHODS: A state-wide retrospective search of pathology
      databases, allowing near-complete, population-based case identification, was
      conducted to detect live-born infants from January 2000 to December 2014 with GBS
      cultured from blood or cerebrospinal fluid within seven days of age. A nested
      audit of EOGBSD cases comparing two epochs, 2000-2010 and 2011-2014, was
      performed to determine patient characteristics and guideline adherence for each
      case. RESULTS: Mean incidence of EOGBSD in Queensland from 2000 to 2014 was 0.33
      per 1000 live births (SD+/- 0.08) with no changing trend over time. The case
      mortality rate in the 2011-2014 epoch was 1.2% compared to 11.9% in 2000-2004
      (odds ratio (OR) 0.09, 95% confidence interval (CI) 0.002-0.67). The proportion
      of EOGBSD cases who were preterm infants decreased from 29.8% to 13.3% (OR 0.36,
      95% CI 0.14-0.84). Of cases with risk factors in the 2011-2014 epoch, 46%
      received intrapartum antibiotics compared to 25% in 2000-2004 (OR 2.49, 95% CI
      0.86-7.58, P = 0.09). CONCLUSIONS: EOGBSD incidence rate in Queensland remained
      low during 2000-2014. However, both the 2011-2014 case-mortality rate and the
      proportion of preterm cases significantly decreased. Missed opportunities for
      intrapartum chemoprophylaxis remain.

PMID- 30203835
TI  - An unexpected diagnosis: angiosarcoma with bone marrow involvement mimicking a
      myeloproliferative neoplasm.

PMID- 30203836
TI  - The rs2516839 variation of USF1 gene is associated with 4-year mortality of
      nonagenarian women: The Vitality 90+ study.
AB  - Upstream transcription factor 1 (USF1) regulates the transcription of many genes
      related to cell and organism survival processes such as stress and immune
      response, regulation of cellular senesce, and carcinogenesis. In this study, our
      aim was to investigate the effect of USF1 single nucleotide variations (SNVs) on
      longevity in the Vitality 90+ study, a population-based study of nonagenarians
      (90 +/-1 years of age) living in the area of Tampere municipality, Finland.
      Altogether 509 voluntary nonagenarians (115 males, 394 females) were genotyped
      using the 5'-nuclease assay for rs2774279G > A, rs2516839T > C, and rs2073658C >
      T SNVs. During the 4 years of follow-up, the total mortality rate was 64.2%. In
      the study, we found that the frequency of C-allele of rs2516839 among
      nonsurviving nonagenarians (52.5%) was higher than those who survived (41.2%; P =
      0.0006, odds ratio = 1.575, 95% confidence interval [CI]: 1.215-2.041).
      Furthermore, carriage of this variation and its haplotypes had a significant
      gender by genotype interaction (P < 0.05) on mortality. Kaplan-Meier log-rank
      test during 4-years of follow-up showed significantly higher mortality rate in
      the case of CC genotype carriage than other genotype carriages in nonagenarian
      women (P < 0.0001). In addition, after adjusting for age in Cox regression
      analysis, cardiovascular disease, diabetes, infectious disease, dementia, and
      living place (nursing home or home), CC genotype of rs2516839T > C was found to
      be associated with shorter life expectancy in nonagenarian women (hazard ratio =
      2.27; 95% CI, 1.34-3.85 P = 0.002). In conclusion, rs2516839 variation and
      related haplotypes of the USF1 gene are strongly related to all-cause mortality
      in Finnish nonagenarians, especially among women.

PMID- 30203837
TI  - Extreme hyperferritinaemia, soluble interleukin-2 receptor, and haemophagocytic
      lymphohistiocytosis.

PMID- 30203838
TI  - Utilization and determinants of follow-up colonoscopies within 6 years after
      screening colonoscopy: Prospective cohort study.
AB  - Previous studies have reported that repeat colonoscopies were often not conducted
      in the recommended time interval after screening colonoscopy. We prospectively
      followed participants of screening colonoscopy from Germany for 6 years to
      investigate utilization and determinants of repeat colonoscopies. In a
      longitudinal study on the effectiveness of screening colonoscopy in the state of
      Saarland (Germany), participants who had a screening colonoscopy between 2005 and
      2007 were contacted by mail 6 years after screening and requested to fill in a
      standardized questionnaire on utilization of repeat colonoscopies. For all
      colonoscopies reported, colonoscopy and histology reports were requested from the
      physician(s). Of 6,407 screening participants, 2,212 (35%) have utilized another
      colonoscopy. Among participants with negative findings at screening (no
      adenomas), 962 (22%) had a subsequent colonoscopy within 6 years from screening,
      accounting for 43% of all patients with a repeat colonoscopy. Family history of
      CRC and detection of hyperplastic polyps were found to be determinants of higher
      repeat colonoscopy use. As many as 44% of the participants with low-risk adenomas
      (N = 509) and 39% with high-risk adenomas (N = 290) at screening did not utilize
      surveillance colonoscopy within 6 years. Utilization was better with higher
      school education, prior cancer screening participation and if high-risk adenomas
      were detected, lower among current smokers and lowest among participants >=70
      years. New strategies will be required considering determinants of adherence to
      avoid unnecessary colonoscopies and to improve utilization of surveillance
      according to recommended time intervals among patients at higher risk of CRC in
      the future.

PMID- 30203839
TI  - Predictors of response to anti-IL6 monoclonal antibody therapy (siltuximab) in
      idiopathic multicentric Castleman disease: secondary analyses of phase II
      clinical trial data.
AB  - Siltuximab is the only US Food and Drug Administration-approved treatment for
      idiopathic multicentric Castleman disease (iMCD), a rare haematological disorder
      associated with substantial morbidity and mortality. Although siltuximab induces
      a response in a significant proportion of iMCD patients via interleukin 6 (IL6)
      neutralization, it is not universally effective. To develop a predictive model of
      response, we performed an in-depth analysis of 38 baseline laboratory parameters
      in iMCD patients from the phase II siltuximab trial who met criteria for
      treatment response or treatment failure. Univariate analyses identified eight
      baseline laboratory parameters that were significantly different between
      responders and treatment failures: albumin, immunoglobulin G (IgG),
      immunoglobulin A, C reactive protein (CRP), fibrinogen, haemoglobin, sodium and
      triglycerides. Stepwise logistic regression analysis of these candidate
      parameters identified a top performing model that included fibrinogen, IgG,
      haemoglobin and CRP. Based on cross-validation of the final multivariate logistic
      regression model, the model accurately discriminated responders from those who
      failed treatment (area under the receiver operator characteristic curve 0.86, 95%
      confidence interval: 0.73-0.95). All four laboratory parameters associated with
      response to siltuximab have biological relationships with IL6 and acute
      inflammation. Our model suggests that iMCD patients with laboratory evidence of
      an inflammatory syndrome are the best candidates for siltuximab therapy.

PMID- 30203840
TI  - Preventive parenting intervention during childhood and young black adults'
      unhealthful behaviors: a randomized controlled trial.
AB  - OBJECTIVE: Lifestyle variables such as drug use and excessive weight gain
      contribute to adult morbidity and mortality. This study was designed to determine
      whether participation in a preventive intervention designed to enhance supportive
      parenting can reduce drug use and body mass index (BMI) in young Black adults
      from disadvantaged neighborhoods. METHOD: This study was conducted in the rural
      southeastern United States. Black parents and their 11-year-old children (517
      families) were assigned randomly to the Strong African American Families (SAAF)
      prevention trial or a control condition. Data assessing neighborhood
      socioeconomic status and supportive parenting were obtained when the youths were
      ages 11 and 16. When youths were ages 19-21 and 25, drug use and BMI were
      measured. RESULTS: As hypothesized, significant three-way interactions were
      detected among neighborhood disadvantage, prevention condition, and gender for
      BMI (B = 3.341, p = .009, 95% CI [0.832, 5.849]) and substance use (B = -0.169, p
      = .049, 95% CI [-0.337, -0.001]). Living in a disadvantaged neighborhood during
      adolescence was associated with increased drug use among young men in the control
      group (simple-slope = 0.215, p < .003) but not among those in the SAAF condition
      (simple-slope = 0.030, p = .650). Neighborhood disadvantage was associated with
      elevated BMI among young women in the control group (simple-slope = 3.343, p <
      .001), but not in the SAAF condition (simple-slope = 0.204, p = .820).
      CONCLUSIONS: The results suggest that participation during childhood in a
      preventive intervention to enhance supportive parenting can ameliorate the
      effects of life in a disadvantaged neighborhood on men's drug use and women's BMI
      across ages 19-25 years. These findings suggest a possible role for parenting
      enhancement programs in narrowing health disparities.

PMID- 30203841
TI  - Avatrombopag, an oral thrombopoietin receptor agonist: results of two double
      blind, dose-rising, placebo-controlled Phase 1 studies.
AB  - Avatrombopag is an oral thrombopoietin receptor agonist that has been recently
      approved for treating thrombocytopenia in chronic liver disease patients needing
      invasive procedures. Clinical trials supporting this new treatment were guided by
      two double-blind, dose-rising, placebo-controlled Phase 1 studies in healthy
      adults reported here that assessed safety, tolerability and pharmacokinetic
      profile of avatrombopag, and its effect on platelet counts. Subjects were
      randomised (2:1) in the single-dose study (N = 63) to avatrombopag (1, 3, 10, 20,
      50, 75 and 100 mg) or placebo, and in the multiple-dose study (N = 29) to
      avatrombopag (3, 10 and 20 mg) or placebo daily for 14 days. There were no
      serious adverse events (AEs), dose-limiting toxicities, deaths, AEs causing
      withdrawal, thromboses or liver function abnormalities. In both studies,
      avatrombopag peak concentration and exposure increased proportionally relative to
      dose; half-life was 18-21 h and independent of dose, supporting once-daily
      dosing. Effects on platelet counts depended on dose, concentration and treatment
      duration. Platelet count increases began 3-5 days post-administration, with
      maximum changes of >370 * 109 /l over baseline with 20 mg daily after 13-16 days.
      These data support continued development of avatrombopag for treatment of other
      thrombocytopenic conditions and provide important guidance for the haematologist
      in the use of this new thrombopoietin receptor agonist.

PMID- 30203842
TI  - Histology of dental long-period biorhythms in Canis familiaris.
AB  - Our objective is to assess variation in Havers-Halberg oscillation (HHO)
      periodicities among domestic dogs (Canis familiaris). The HHO is hypothesized to
      be a hypothalamic-generated biorhythm coordinating multiple life history
      variables including body mass and lifespan. Dogs have a broad mass range spanning
      two orders of magnitude, but this variation has been shown to result from
      selection on very few genetic loci, and dogs have low variation in other life
      history traits. Therefore, we predict that HHO variation will not be correlated
      to body mass among domestic dogs, as it is in anthropoid primates. To test the
      prediction, we examined dog HHO periodicity via manifestations in tooth enamel
      and dentine, quantifying HHO rhythm histologically. HHO rhythm is reflected in
      teeth as the number of days between secretion of successive striae of Retzius
      (enamel) and Andresen lines (dentine), a value referred to as Retzius periodicity
      (RP). We counted ca. 24-h growth lines between successive Retzius and Andresen
      lines to determine RP in histological thin-sections from canine teeth of 19 dogs,
      representing different breeds and sizes. To test our hypothesis, we regressed RP
      periodicity against body mass data. Dogs have low RP variation for their body
      mass range, with a modal periodicity of 5 days and a range of 4-6 days. RP was
      not significantly correlated with body mass. We conclude that mass variation in
      dogs does not seem driven by HHO physiology, consistent with findings that IGF1
      variants produce dog mass variation. However, low RP (and by extension HHO)
      variation is consistent with low variation in dog lifespan and gestation,
      suggesting that dog life history may still be governed by HHO mechanisms even if
      body mass does not reflect this.

PMID- 30203843
TI  - Birds of a feather: Is matching based on shared interests and characteristics
      associated with longer youth mentoring relationships?
AB  - Youth mentoring practitioners and researchers have shown a growing interest in
      determining the ways in which mentor-youth matching practices might influence the
      duration and effectiveness of mentoring relationships. The current project tested
      whether mentor-youth similarities at baseline, in terms of demographic variables
      and interests in certain activities (e.g., sports, art), predicted a longer
      duration of mentoring relationships. Analyses used baseline and follow-up data
      from over 9,000 youth who participated in community-based mentoring programs in
      the northeastern United States, as well as their volunteer mentors. Racial and
      ethnic similarity between mentor and youth was predictive of longer match
      duration. Moreover, a shared dislike of activities was associated with longer
      matches than either shared interests or discordant interests in activities.
      Findings have important implications for determining the ways in which mentor
      youth matching practices influence the length and effectiveness of mentoring
      relationships.

PMID- 30203844
TI  - Tomato stigma exsertion induced by high temperature is associated with the
      jasmonate signalling pathway.
AB  - High temperature (HT) is becoming an increasingly serious factor in limiting crop
      production with global climate change. During hot seasons, owing to prevailing
      HT, cultivated tomatoes are prone to exhibiting stigma exsertion, which hampers
      pollination and causes fruit set failure. However, the underlying regulatory
      mechanisms of the HT-induced stigma exsertion remain largely unknown. Here, we
      demonstrate that stigma exsertion induced by HT in cultivated tomato is caused by
      more seriously shortened stamens than pistils, which is different from the stigma
      exsertion observed in wild tomato species. Under the HT condition, the different
      responses of pectin, sugar, expansin, and cyclin cause cell wall remodelling and
      differentially localized cell division and selective cell enlargement, which
      further determine the lengths of stamens and pistils. In addition, auxin and
      jasmonate (JA) are implicated in regulating cell division and cell expansion in
      stamens and pistils, and exogenous JA instead of auxin treatment can effectively
      rescue tomato stigma exsertion through regulating the JA/COI1 signalling pathway.
      Our findings provide a better understanding of stigma exsertions under the HT
      condition in tomato and uncover a new function of JA in improving plant abiotic
      stress tolerance.

PMID- 30203845
TI  - Investigational use of PEGylated carboxyhemoglobin bovine in a Jehovah's Witness
      with hemorrhagic shock.
AB  - BACKGROUND: Jehovah's Witnesses pose a clinical challenge in the setting of
      critical anemia. Most do not accept transfusions, but some accept hemoglobin
      based oxygen carriers on a compassionate-use basis. PEGylated carboxyhemoglobin
      bovine (PCHB) is an acellular dual-action carbon monoxide (CO)-releasing and
      oxygen transfer agent currently being investigated in Phase II clinical trials.
      CASE REPORT: We present the case of a 42-year-old Jehovah's Witness with an acute
      upper gastrointestinal bleed and hemorrhagic shock who required emergent PCHB for
      stabilization during lifesaving interventions. After PCHB infusion, the patient's
      shock and encephalopathy improved with decreased vasopressor requirement. Through
      gastroenterology and interventional radiology procedures, the patient's bleeding
      stabilized. While receiving five additional doses of PCHB and other supportive
      therapies (iron, folate, vitamin B12, darbepoetin alfa), the patient was
      extubated and weaned off vasopressors. CONCLUSIONS: PCHB was used to stabilize
      (bridge) a critically ill anemic patient for lifesaving interventions without
      adverse effects. Additional studies are warranted to explore the drug's safety
      profile and efficacy in patients declining blood products.

PMID- 30203846
TI  - Sense of place attitudes and quality of life outcomes among African residents in
      a multicultural Australian society.
AB  - The study examines the association between sense of place (SOP) attitudes (e.g.,
      place attachment, place identity, and place dependence) and health-related
      quality of life (HQOL) in a sample of 261 African residents in New South Wales
      (Australia). Participants completed measures of the Sense of Place Scale, the
      World Health Organization Quality of Life-BREF questionnaire, and demographic
      variables. Study findings are as follows: (a) levels of SOP and place attachment
      are positively associated with all outcomes of HQOL; (b) place identity is also
      positively related to HQOL in terms of better environmental health, psychological
      health, and physical health, but not statistically significant for social
      relationship and general QOL; (c) place dependence is statistically associated
      with outcomes of HQOL, except for general QOL which remained insignificant in
      both the unadjusted and adjusted models. Further ad hoc analyses suggest that
      African residents from Eastern Africa are more likely to develop the "aussie"
      place identity than those from Central Africa; and (e) African migrants who have
      been residents of Australia for more than 5 years, and those who are less
      educated are more likely to have a stronger SOP and to develop place attachment
      and behavioral place commitments compared with newly arrived and educated
      migrants, respectively. Study limitations and implications are carefully
      discussed.

PMID- 30203847
TI  - Advances in mass spectrometry-based glycoproteomics.
AB  - Protein glycosylation, an important PTM, plays an essential role in a wide range
      of biological processes such as immune response, intercellular signaling,
      inflammation, and host-pathogen interaction. Aberrant glycosylation has been
      correlated with various diseases. However, studying protein glycosylation remains
      challenging because of low abundance, microheterogeneities of glycosylation
      sites, and poor ionization efficiency of glycopeptides. Therefore, the
      development of sensitive and accurate approaches to characterize protein
      glycosylation is crucial. The identification and characterization of protein
      glycosylation by MS is referred to as the field of glycoproteomics. Methods such
      as enrichment, metabolic labeling, and derivatization of glycopeptides in
      conjunction with different MS techniques and bioinformatics tools, have been
      developed to achieve an unequivocal quantitative and qualitative characterization
      of glycoproteins. This review summarizes the recent developments in the field of
      glycoproteomics over the past 6 years (2012 to 2018).

PMID- 30203848
TI  - Establishment of a high-sensitivity reporter system in mammalian cells for
      detecting juvenoids using juvenile hormone receptors of Daphnia pulex.
AB  - Environmental waters are polluted by various chemicals originating from human
      activities. Recently, the environmental risk of juvenile hormones (JHs) to
      aquatic microcrustaceans has been recognized by risk assessors and researchers.
      JH is a major arthropod hormone that regulates molting and reproduction and has
      analogs that have been used as insect growth regulators. JHs are known to disturb
      the sex determination system of Daphnia, which is a keystone animal in limnetic
      ecosystems and is not the target of extermination. To assess the risk of
      contaminant chemicals and to protect biodiversity, reliable methods for detecting
      such chemicals are essential. In this study, we attempted to establish a
      practical in vitro reporter assay system for detecting chemicals with JH
      activity. Using a newly constructed reporter vector (modified from the JH
      response element of Tribolium castaneum Kruppel homolog 1, which is a major JH
      responsive gene in insects), strong JH-dependent transcriptional activity (>40
      fold activation) was found in Chinese hamster ovary cells that express JH
      receptors of Daphnia pulex. Dose-response analysis conducted on several JH and
      non-JH chemicals revealed that the established reporter assay system has strict
      specificity to JH chemicals, and the half maximum effective concentration (EC50 )
      was between 10-7 and 10-9  m. These results suggest that the new system is a
      rapid and economical method for assessing the environmental risk of JH-active
      chemicals.

PMID- 30203850
TI  - HandS ECMO: Preliminary Experience With "Hub and Spoke" Model in Neonates With
      Meconium Aspiration Syndrome.
AB  - We aim to evaluate clinical outcomes of emergent extracorporeal membrane
      oxygenation (ECMO) implantation in newborns with life-threatening meconium
      aspiration syndrome (MAS) in peripheral hospitals with Hub and Spoke (HandS)
      setting. We retrospectively reviewed all neonates presenting with MAS, with no
      other comorbidities, treated with HandS ECMO, in peripheral hospitals. Team
      activation time (TAT) was described as the time from first alerting call to ECMO
      support initiation. From May 2014 to December 2016, 4 patients met our inclusion
      criteria. In addition, 2 cases occurred on the same day, requiring a second
      simultaneous HandS ECMO team activation. All patients were younger than 8 days of
      life (1, 1, 4, and 7), with a mean BSA 0.21 +/- 0.03m2 , and TAT of 203, 265,
      320, and 340 min. One patient presented ventricular fibrillation after priming
      administration. Veno-arterial ECMO was established in all patients after
      uneventful surgical neck vessels cannulation (right carotid artery and jugular
      vein). Mean time from skin incision to ECMO initiation was 19 +/- 1.4 min. Mean
      length of ECMO support was 2.75 +/- 1.3 days. All patients were weaned off
      support without complications. At a mean follow up of 20.5 +/- 7.8 months, all
      patients are alive, with no medications, normal somatic growth, and
      neuropsychological development. MAS is a life-threatening condition that can be
      successfully managed with ECMO support. A highly trained multidisciplinary HandS
      ECMO team is crucial for the successful management of these severely ill newborns
      in peripheral hospitals.

PMID- 30203849
TI  - Regulating nociceptive transmission by VGluT2-expressing spinal dorsal horn
      neurons.
AB  - Vesicular glutamate transporter-2 (VGluT2) mediates the uptake of glutamate into
      synaptic vesicles in neurons. Spinal cord dorsal horn interneurons are highly
      heterogeneous and molecularly diverse. The functional significance of VGluT2
      expressing dorsal horn neurons in physiological and pathological pain conditions
      has not been explicitly demonstrated. Designer receptors exclusively activated by
      designer drugs (DREADDs) are a powerful chemogenetic tool to reversibly control
      neuronal excitability and behavior. Here, we used transgenic mice with Cre
      recombinase expression driven by the VGluT2 promoter, combined with the
      chemogenetic approach, to determine the contribution of VGluT2-expressing dorsal
      horn neurons to nociceptive regulation. Adeno-associated viral vectors expressing
      double-floxed Cre-dependent Galphaq-coupled human M3 muscarinic receptor DREADD
      (hM3D)-mCherry or Galphai-coupled kappa-opioid receptor DREADD (KORD)-IRES
      mCitrine were microinjected into the superficial spinal dorsal horn of VGluT2-Cre
      mice. Immunofluorescence labeling showed that VGluT2 was predominantly expressed
      in lamina II excitatory interneurons. Activation of excitatory hM3D in VGluT2
      expressing neurons with clozapine N-oxide caused a profound increase in neuronal
      firing and synaptic glutamate release. Conversely, activation of inhibitory KORD
      in VGluT2-expressing neurons with salvinorin B markedly inhibited neuronal
      activity and synaptic glutamate release. In addition, chemogenetic stimulation of
      VGluT2-expressing neurons increased mechanical and thermal sensitivities in naive
      mice, whereas chemogenetic silencing of VGluT2-expressing neurons reversed pain
      hypersensitivity induced by tissue inflammation and peripheral nerve injury.
      These findings indicate that VGluT2-expressing excitatory neurons play a crucial
      role in mediating nociceptive transmission in the spinal dorsal horn. Targeting
      glutamatergic dorsal horn neurons with inhibitory DREADDs may be a new strategy
      for treating inflammatory pain and neuropathic pain.

PMID- 30203851
TI  - Action potential and calcium dependence of tonic somatodendritic dopamine release
      in the Substantia Nigra pars compacta.
AB  - Despite the importance of somatodendritic dopamine (DA) release in the Substantia
      Nigra pars compacta (SNc), its mechanism remains poorly understood. Using a novel
      approach combining fast-scan controlled-adsorption voltammetry (FSCAV) and single
      unit electrophysiology, we have investigated the mechanism of somatodendritic
      release by directly correlating basal (non-stimulated) extracellular DA
      concentration ([DA]out ), with pharmacologically-induced changes of firing of
      nigral dopaminergic neurons in rat brain slices. FSCAV measurements indicated
      that basal [DA]out in the SNc was 40.7 +/- 2.0 nM (at 34 +/- 0.5 degrees C),
      which was enhanced by amphetamine, cocaine, and L-DOPA, and reduced by VMAT2
      inhibitor, Ro4-1284. Complete inhibition of firing by TTX decreased basal [DA]out
      , but this reduction was smaller than the effect of D2 receptor agonist,
      quinpirole. Despite similar effects on neuronal firing, the larger decrease in
      [DA]out evoked by quinpirole was attributed to cell membrane hyperpolarization
      and greater reduction in cytosolic free Ca2+ ([Ca2+ ]in ). Decreasing
      extracellular Ca2+ also reduced basal [DA]out , despite increasing firing
      frequency. Furthermore, inhibiting L-type Ca2+ channels decreased basal [DA]out ,
      although specific Cav 1.3 channel inhibition did not affect firing rate.
      Inhibition of sarcoplasmic/endoplasmic reticulum Ca2+ -ATPase (SERCA) also
      decreased [DA]out , demonstrating the importance of intracellular Ca2+ stores for
      somatodendritic release. Finally, in vivo FSCAV measurements showed that basal
      [DA]out in the SNc was 79.8 +/- 10.9 nM in urethane-anesthetized rats, which was
      enhanced by amphetamine. Overall, our findings indicate that although tonic
      somatodendritic DA release is largely independent of action potentials, basal
      [DA]out is strongly regulated by voltage-dependent Ca2+ influx and release of
      intracellular Ca2+ .

PMID- 30203852
TI  - A new validated HPLC method for the determination of levodopa: Application to
      study the impact of ketogenic diet on the pharmacokinetics of levodopa in
      Parkinson's participants.
AB  - A simple, accurate, and reproducible HPLC-UV method has been developed and
      validated for the quantification of levodopa (l-Dopa) in human plasma. The method
      involves a simple protein precipitation procedure to extract both l-Dopa and
      methyldopa, the internal standard. The chromatographic analysis was achieved on a
      Shimadzu LC 20A HPLC system equipped with a Zorbax Eclipse XDB C18 column and an
      isocratic mobile phase consisting of 20 mm KH2 PO4 (pH 2.5) and methanol (95:5,
      v/v) run at a flow rate of 1 mL/min. The UV detection wavelength was set at 230
      nm. The method exhibited good linearity (R2  > 0.999) over the assayed
      concentration range (0.1-10 MUg/mL) and demonstrated good intra- and inter-day
      precision and accuracy (relative standard deviations and the deviation from
      predicted values were <15%). This method was also successfully applied for
      studying the potential effect of ketogenic diet on the pharmacokinetics of l-Dopa
      in Parkinson's participants. Our data analysis indicates that ketogenic diet does
      not significantly affect the pharmacokinetics of l-Dopa.

PMID- 30203853
TI  - Tacrolimus diffusion across the peripheral mononuclear blood cell membrane:
      impact of drug transporters.
AB  - Measuring tacrolimus (TAC) concentration in peripheral blood mononuclear cells
      (PBMCs) could better reflect the drug effect on its target (calcineurin (CaN) in
      lymphocytes) than whole blood concentrations. Mechanisms influencing TAC
      diffusion into PBMC are not well characterized. This work aimed at describing, ex
      vivo, TAC diffusion kinetics into PBMC and investigating the contribution of
      membrane transporters to regulate TAC intracellular concentration as well as the
      impact on CaN activity. PBMCs were incubated with TAC for 5 min to 4 h and under
      several experimental conditions: 37  degrees C (physiological conditions), 4 
      degrees C (inhibition of influx and efflux active transport), 37  degrees C +
      transporter inhibitors (verapamil, carvedilol, and probenecid and
      bromosulfophthalein, respectively, inhibitors of P-gp, OAT, and OATP). TAC
      concentration and CaN activity were measured in PBMC using liquid chromatography
      coupled with mass spectrometry. TAC intra-PBMC concentration was maximal after 1
      h of incubation. Mean TAC PMBC concentrations were significantly lower in samples
      incubated at 4  degrees C compared to the 37  degrees C groups. Addition of
      verapamil slightly increased TAC accumulation in PBMC while other inhibitors had
      no effect. A significant correlation was found between TAC intra-PBMC
      concentration and the level of inhibition of CaN. Using an ex vivo cellular
      model, these results suggest that P-gp is involved in the drug efflux from PBMC
      while influx active transporters likely to regulate TAC intra-PBMC disposition
      remain to be identified. TAC concentration in PBMC is correlated with its
      pharmacodynamic effect. Then, TAC intra-PBMC concentration appears to be a
      promising biomarker to refine TAC therapeutic drug monitoring.

PMID- 30203854
TI  - Efficacy of inhaled budesonide for the treatment of severe equine asthma.
AB  - BACKGROUND: Corticosteroids are the most potent drugs for the control of severe
      equine asthma, but adverse effects limit their chronic systemic administration.
      Inhaled medications allow for drug delivery directly into the airways, reducing
      the harmful effects of these drugs. OBJECTIVES: To evaluate the efficacy of
      inhaled budesonide specifically formulated for the equine use and administered by
      a novel inhalation device in horses with severe asthma. STUDY DESIGN:
      Experimental studies in horses with naturally occurring asthma with cross-over,
      randomised, blinded experimental designs. METHODS: In Study 1, budesonide (1800
      MUg twice daily) administered using a novel Respimat(r) based inhaler was
      compared to i.v. dexamethasone (0.04 mg/kg). In Study 2, 3 doses of budesonide
      (450, 900, and 1800 MUg) were compared to oral dexamethasone (0.066 mg/kg). Lung
      function, bronchoalveolar fluid cytology (Study 1), CBC, serum chemistry, and
      serum cortisol and adrenocorticotropic hormone (ACTH) values were evaluated.
      RESULTS: In Study 1, there was a marked and significant improvement in the lung
      function of all horses treated with budesonide and dexamethasone. Neutrophil
      percentages in bronchoalveolar fluid decreased in all horses treated with
      dexamethasone and in four of six horses treated with budesonide. Serum cortisol
      and blood ACTH concentrations decreased with both treatments. In Study 2, there
      was a significant improvement in the lung function with all dosages of
      budesonide, and the effects of higher dosages were comparable to those of
      dexamethasone. Dexamethasone and budesonide at the two higher dosages induced a
      significant decrease of cortisol concentrations. MAIN LIMITATIONS: The
      Respimat(r) based inhaler is not currently commercially available. CONCLUSIONS:
      Administration of budesonide with the Respimat(r) based inhaler provided dose
      dependent relief of airway obstruction in horses with severe asthma, but also a
      suppression of serum cortisol.

PMID- 30203855
TI  - Bioactive compound from Aspergillus terreusDMTMGK004 synergistically contributes
      towards potential anti-pathogenicity.
AB  - This study focused on the evaluation of fungal compound for their anti-pathogenic
      potential against respiratory pathogens. Soil samples were collected from various
      geographical regions in Madurai, fungal strain was isolated and identified as
      Aspergillus terreusDMTMGK004 (MGK004). Secondary metabolites were extracted and
      evaluated for antioxidant potential. It exhibited significantly high anti
      proliferative property against gastric adenocarcinoma (AGS) cell lines.
      Antimicrobial activity against Gram positive (Streptococcus pneumoniae) and Gram
      negative (Klebsiella pneumoniae and Haemophilus influenzae) respiratory pathogens
      were analysed and the minimum inhibitory concentration (MIC) values were
      determined. Furthermore, the time-killing assay illustrated that the metabolite
      eliminates 50% of the vegetative cells within few hours of the treatment. From
      the spectral data, the major functional groups present in the compound were
      determined as carbonyl group and phenolic hydroxyl group which contribute towards
      its bioactivity. The compound significantly depreciates the production of
      extracellular polysaccharides which results in the weakening of biofilm
      architecture and resistance towards serum killing and phagocytosis. It also
      induced cell membrane damage which leads to protein and nucleic acid leakage.
      Hence, the results of the present study could provide a better insinuation
      towards the formulation of new drug targeting respiratory pathogens. SIGNIFICANCE
      AND IMPACT OF THE STUDY: The ubiquitous fungi Aspergillus terreus is well known
      for its secondary metabolite production. The fungus was evaluated for production
      of antagonistic molecule to reduce the growth of infectious agents causing
      respiratory infections. It exhibited the biological means of antioxidant, anti
      proliferative and anti-pathogenic compound production. The compound exhibits
      killing effect against respiratory pathogens within two hours. It induced cell
      membrane damage leading to protein and nucleic acid leakage. It significantly
      reduced the production of extracellular polysaccharides. The results provide
      needed information to design innovative strategies for targeting pathogenic
      factors of the respiratory pathogens instead of killing it precisely.

PMID- 30203856
TI  - A linear mixed model framework for gene-based gene-environment interaction tests
      in twin studies.
AB  - Interaction between genes and environments (G*E) can be well investigated in
      families due to the shared genes and environment among family members. However,
      the majority of the current tests of G*E interaction between a set of variants
      and an environment are only suitable for studies with unrelated subjects. In this
      paper, we extend several G*E interaction tests to a linear mixed model framework
      to study interaction between a set of correlated environments and a candidate
      gene in families. The correlated environments can either be modeled separately or
      jointly in one model. We demonstrate theoretically that the tests developed by
      modeling correlated environments separately are valid and present a
      computationally fast alternative to detect G*E interaction in families. For
      either strategy, we propose treating the genetic main effects as a random effect
      to reduce the number of main-effect parameters and thus improve the power to
      detect interactions. Additionally, we propose a generalization of a test of
      interaction that adaptively sums the interactions using a sequential algorithm.
      This generalized set of tests, referred to as the sequential algorithm for the
      sum of powered score (Seq-SPU) family of tests, can be expressed as a weighted
      version of the SPU. We find that the adaptive version of our test, Seq-aSPU, can
      outperform aSPU in cases where the interactions effects are in opposite
      directions. We applied these methods to the Minnesota Center for Twin and Family
      Research data set and found one significant gene in interaction with four
      psychosocial environmental factors affecting the alcohol consumption among the
      twins.

PMID- 30203857
TI  - Prognostic indicators for survival in African penguin chicks (Spheniscus
      demersus): A retrospective analysis.
AB  - Mystic Aquarium has successfully maintained an active breeding population of
      African penguins since 1990. Between 1990 and 2015, 477 eggs were laid, 84 of
      which were recommended for rearing according to the SSP Breeding and Transfer
      Plan. Sixty-five percent hatched successfully, and total fertility ranged from
      56% to 78%. Of the 55 hatchlings, 60% of chicks reached fledgling age (80 days).
      Of the 22 chicks that died before fledging, 59% died within 7 days of hatching,
      and 82% within 30 days of hatching. Categories of mortality were broken down into
      the following categories: failure to thrive (in the absence of a definitive cause
      of death) (41%), respiratory disease (32%), parent-associated trauma (13%),
      congenital defects (9%), and gastrointestinal disease (5%). Analysis of
      associated factors identified a significant correlation between the hatch weights
      of chicks that survived beyond day 7 (60.5-66.0 g), and those that did not (49.5
      59.5 g). Further positive correlations were established between chick hatch
      weight and both dam body weight, and egg weight. While hand-reared chicks gained
      weight more slowly than their parent-reared counterparts, results showed that
      rearing method had no significant impact on survival. The findings of this study
      provide a baseline for assessing reproductive success and chick mortality, and
      supply prognostic indicators for evaluating chick success in managed African
      penguin populations.

PMID- 30203858
TI  - How the public autopsy of a slave Joice Heth launched P.T. Barnum's career as the
      Greatest Showman on Earth.
AB  - P.T. Barnum's career as the Greatest Showman on Earth began in 1835, when he
      "leased" and then publically exhibited a frail African American slave Joice Heth,
      who was reportedly the 161-year-old former nursemaid of George Washington,
      throughout New England; the contract was a lease, as slave ownership had recently
      become illegal in northern states. Barnum exhibited Heth 6 days a week for up to
      12 hr a day. Under this grueling schedule, Heth became ill and died while under
      contract. Barnum sold tickets for her autopsy, which was performed by David L.
      Rogers, an accomplished New York surgeon, in front of an audience of 1,500 paying
      customers. Roger's autopsy determined that Heth was no more than 80 years old,
      and the penny newspapers, a new form of public media, called this a "humbug" and
      then published dozens of fabricated "fake news" stories about Barnum, Rogers, and
      Heth. Barnum and his business partner generated valuable publicity by telling
      different penny newspapers different stories. This whole spectacle launched
      Barnum's career as an entertainer. Five years earlier, Rogers performed a public
      dissection of Charles Gibbs, an infamous Caribbean pirate who was tried,
      convicted, and hung in New York City. This article describes the bizarre nature
      of American politics and culture in the 1830s that made all of these seem normal.
      I will also distinguish between "public dissection" and "public autopsy," and put
      these into an historical context. Finally, I will address the macabre concept of
      autopsy as a form of entertainment. Clin. Anat. 31:956-965, 2018. (c) 2018 Wiley
      Periodicals, Inc.

PMID- 30203859
TI  - Response to Letter to Editor by D'Antoni, AV & Mtui, EP (2018).

PMID- 30203860
TI  - Uncertainties of calculated Cramer-Rao lower bounds: implications for
      quantitative MRS.
AB  - PURPOSE: To investigate the uncertainties on relative Cramer-Rao lower bound
      (rCRB) estimates and demonstrate their biasing effects in MRS quantification.
      THEORY AND METHODS: Simulations were performed to calculate the distribution of
      the computed rCRB (noted rCRB*) for several rCRB levels. One hundred thousand
      simulations per rCRB value were performed on simulated NMR signals containing
      either 1 signal (singlet) or 2 partially overlapping signals. False-positive and
      false-negative risks were compiled for different threshold levels. rCRB*
      distribution was experimentally checked on a deuterated water sample using a 9.4
      Tesla vertical magnet. RESULTS: Simulations showed that (1) rCRB* distribution is
      asymmetrical, with a right-tailed distribution increasing the risk of accepting
      false-positive data (i.e., accepting an rCRB* value whereas the true rCRB value
      is higher than the threshold level) and (2) distribution broadness increases with
      increasing rCRB level. Simulations with overlapped peaks lead to more inaccuracy
      in the rCRB estimation. Probabilities of false detection increase with increasing
      threshold level. CONCLUSION: Analyzing results thanks to a CRB (or rCRB) based on
      experimental measurements might lead to misinterpretations. To exploit the rCRB*
      as rejection criteria, a conservative threshold level of 20% is recommended in
      order to limit the probability of false alarms.

PMID- 30203861
TI  - What the 'ell? testicle is a diminutive!
AB  - The frequency of diminutives in anatomical Latin has often been noted to be high,
      but that is not unusual in post-classical Latin. Although the connotation of
      "little" is well known, many of the diminutives in anatomical Latin do not have
      that meaning. The morphology of regular, irregular and secondary diminutives is
      presented, along with that of adjectival forms of diminutives. Several
      transgendered and malformed diminutives are discussed. This article is protected
      by copyright. All rights reserved.

PMID- 30203862
TI  - Variations in pelvic dimensions: An anatomical and computed tomography study.
AB  - The anterior pelvic plane (APP) is a useful anatomical reference with both
      clinical and research applications in orthopedic surgery and rehabilitation
      medicine. It is used as a marker for computer-assisted total hip replacement and
      image-guided assessment of the hip center in clinical gait analysis. Despite its
      common use, no published data exist on the variations in height and width in an
      adult population. The aim of this study was to determine the range of dimensions
      for the anterior pelvic plane found in the Scottish adult population. Thirty-five
      human cadavers and 100 pelvic computed tomography (CT) scans were examined.
      Pelvic height and width were measured, and the ratios were determined. The mean
      width and height for combined cadaver and CT pelves were found to be 238.0 mm (SD
      20.1, range 188.3-273.8) and 92.7 mm (SD 10.5, range 71.2-114.7), respectively.
      The mean width-to-height ratio for all pelves was 2.59 (SD 0.31, range 1.73
      3.50). There were no statistically significant differences in means between males
      and females. The variations of APP dimensions within an adult population are
      presented. These will be of value in the validation of algorithms for computer
      navigation and hip joint center calculation in total hip arthroplasty and gait
      analysis. Furthermore, differences in dimensions between cadaveric and CT
      measurements have been shown which may have implications for further research and
      the validity of reference data dependent on data-point acquisition. Clin. Anat.
      31:981-987, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 30203863
TI  - The dorsal skin structure contributes to the surface bacteria populations of
      Sunda Porcupine (Hystrix javanica).
AB  - Skin becomes the largest organ in the body and protects its own inner layer. The
      structure and chemical composition of the skin contribute to skin condition and
      affect the habitat of certain bacteria. The Sunda Porcupine is one of endemic
      animals of Indonesia which possesses quill as the main derivate of its skin and
      as a defence tool against predators. The present study used nine adults (five
      females and four males) of Sunda Porcupine and aimed to observe the correlation
      of skin structure with bacterial population at the surface level. The skin was
      wavy due to the protrusion of quill follicle orifices on the skin surface and
      formed clusters. The skin of Sunda Porcupine was also wrinkled and had a lot of
      flakiness. Histologically, the skin was composed of epidermis, dermis, hypodermis
      and subcutaneous muscle. The quill follicles and their properties were the
      dominant structure component of the skin. No sweat gland was observed in the skin
      of the Sunda Porcupine, and sebaceous gland was found only around quill and hair
      follicles. The bacterias identified in the skin were Staphylococcus aureus, S.
      epidermidis, Micrococcus sp. and Salmonella sp. When compared, the bacterial
      population was higher in the lumbosacral region than in the thoracodorsal region,
      but the difference was not significant. The density of quill clusters was
      negatively correlated to the bacterial population. It was suggested the structure
      of the skin has contribution to bacterial population in dorsal trunk of the Sunda
      Porcupine.

PMID- 30203864
TI  - Design of Chiral Bifunctional Dialkyl Sulfide Catalysts for Regio-, Diastereo-,
      and Enantioselective Bromolactonization.
AB  - Although a wide variety of chiral organocatalysts have been developed for
      asymmetric transformations, effective chiral dialkyl sulfide organocatalysts
      remain relatively rare and under-developed, despite the potential utility of
      dialkyl sulfide catalysts. Herein, we report the development of chiral
      bifunctional dialkyl sulfide catalysts possessing a urea moiety for regio-,
      diastereo-, and enantioselective bromolactonization. The importance of the
      bifunctional design of chiral sulfide catalysts was clearly demonstrated in the
      present work. The roles of both the sulfide and urea moieties of the catalyst
      were clarified based on the results of experimental and theoretical
      investigation.

PMID- 30203865
TI  - Response of protein S100B to playing American football, lifting weights, and
      treadmill running.
AB  - OBJECTIVE: To determine if serum S100B increases similarly as a result of playing
      American football compared to exercise alone. METHODS: Serum S100B was measured
      in division III collegiate football players before and after every home game
      during a single football season. Serum S100B was also measured before and after
      subjects walked on a treadmill for 30 minutes at a leisurely pace, ran on a
      treadmill while wearing and not wearing a football helmet at 6 mph for 8 minutes,
      and performed low-, moderate-, or high-intensity resistance exercise. RESULTS:
      Serum S100B increased significantly (P < 0.05) when subjects played in a football
      game, ran on a treadmill, or performed moderate-intensity resistance exercise.
      Pre-game serum S100B did not accumulate throughout the football season in any of
      the players (P > 0.05). The increase in serum S100B during football games was
      moderately and significantly correlated with both the number of hits (R2  =
      0.407) and the number of plays (R2  = 0.484) that each player experienced (P <
      0.001). Post-game serum S100B was greater in football players who played more
      than 50 plays compared to those players who played <50 plays, subjects who
      exercised on a treadmill, or subjects performing resistance exercise (P < 0.05).
      CONCLUSION: It is unclear if the higher S100B concentration in football players
      playing at least 50 plays was caused by exercise or hits. Therefore, if serum
      S100B is to be used as a biomarker of impacts, and possible brain injury in
      sport, exercise time and intensity should be taken into account as confounding
      variables.

PMID- 30203867
TI  - Effect of adding different levels of caffeine in the extender on some biochemical
      constituents, enzymatic activities and physical characteristics of chilled and
      frozen ram semen.
AB  - Two experiments were carried out to determine the efficiency of supplementation
      of ram semen extender with caffeine on chilled storage and frozen capacity of
      spermatozoa. In the first experiment, eighty ejaculates were collected by an
      artificial vagina from five adult Barki rams, aged 2-3 years and weighted 45.0 +/
      2.0 kg throughout the experimental period (January to February 2017). The
      ejaculates were pooled and diluted (1:10) with tris-citric egg yolk extender and
      were split into five groups. Group 1 served as control, whereas groups 2-5 were
      supplemented with 0.1, 0.2, 0.3 and 0.4 mM caffeine. All diluted semen specimens
      were evaluated for physical characteristics immediately after dilution (T0 ) and
      throughout preservation period of 48 hr at 4 degrees C. Simultaneously, oxidative
      stress and indices such as total antioxidant capacity (TAC), malondialdehyde
      concentrations (MDA) and alkaline transaminase (AKP) concentrations and value of
      resazurin reduction test (RRT) were determined. In the second experiment, the raw
      pooled ejaculates were diluted (1:10) with glycerolated tris-citric egg yolk
      extender, receiving the previously mentioned caffeine levels. The post-thaw
      assessment of cryopreserved spermatozoa, in all groups, was conducted by a
      computer-assisted sperm analysis (CASA) system. The results revealed that adding
      caffeine to ram semen extender at low (0.1 mM) or medium (0.2 mM) levels had
      positive impact on both physical characteristics of ram sperm and the enzymatic
      activities compared to the other semen groups. Caffeine supplementation also
      enhanced post-thaw sperm dynamics, which implies its potential as an exogenous
      antioxidant supplement.

PMID- 30203866
TI  - The effect of isometric exercise on pain in individuals with plantar fasciopathy:
      A randomized crossover trial.
AB  - Isometric exercise is commonly recommended for immediate pain relief in
      individuals suffering from lower limb tendinopathies, despite the limited
      evidence supporting its analgesic effect. Due to the similarities between plantar
      fasciopathy and tendinopathies, the aim of this trial was to investigate the
      acute effect of isometric exercise on pain, compared to isotonic exercise, or
      walking, in individuals with plantar fasciopathy. We recruited 20 individuals
      with plantar fasciopathy for this prospectively-registered, participant-blinded,
      randomized, superiority crossover trial (ClinicalTrials.gov: NCT03264729).
      Participants attended three exercise sessions (isometric, isotonic, or walking)
      in a randomized order, within a 2-week period. Both isometric and isotonic
      exercises were performed standing with the forefoot on a step bench, while
      walking was performed barefoot. The primary outcome was pain (measured on a 0-100
      mm VAS) during a pain-aggravating activity. Secondary outcomes included pressure
      pain threshold (PPT) under the heel, and plantar fascia thickness (PFT). All
      outcomes were measured before and after each exercise session. There were no
      significant differences between the three exercises on pain (P = 0.753), PPTs (P
      = 0.837), or PFT (P = 0.718). Further, there was no change in pain from before to
      after any of the exercises (isometric exercise 2.7 mm [95% CI: -12.2; 6.8],
      isotonic exercise -3.4 mm [95% CI: -5.0; 11.8], or walking 1.6 mm [95% CI: -16.1;
      12.9]). Contrary to expectations, isometric exercise was no better than isotonic
      exercise or walking at reducing pain in individuals with plantar fasciopathy.
      None of the exercises induced any systematic analgesic effect.

PMID- 30203868
TI  - Photocatalytic Properties Dependent on the Interfacial Defects of Intergrains
      within TiO2 Mesocrystals.
AB  - The regulation of interfacial defects of nanocrystals aligned orderly in a
      superstructured photocatalyst is an effective approach to improve the
      photocatalytic performance. However, the synthesis of ordered self-assemblies
      with abundant interfacial defects and reactive sites is hard to achieve, and
      applications are limited due to the unclear physicochemical properties, which
      result from the unique mesocrystalline microstructures. It is reported herein
      that the photocatalytic properties depend on the interfacial defects of
      intergrains in anatase TiO2 mesocrystals (TMCs). Research reveals that the
      photocatalytic activity largely depends on defects, such as lattice distortion
      and oxygen vacancies, which are located at highly aligned interfaces of
      intergrains within TMCs. Moreover, the mesocrystalline TiO2 photocatalysts
      exhibit higher photocatalytic performance in organic degradation and hydrogen
      evolution, compared with single crystals and polycrystals; this can be ascribed
      to an appropriate amount of interfacial defects at the intergrains and improved
      carrier separation efficiency through the highly oriented interfaces. In
      addition, the photocatalytic performance of the TMCs could be further improved
      through regulation of defects by undergoing an annealing process under a redox
      atmosphere. This work can provide an avenue to defect engineering for improved
      photocatalytic performance.

PMID- 30203869
TI  - Catalytic Isohypsic-Redox Sequences for the Rapid Generation of Csp3 -Containing
      Heterocycles.
AB  - Cross-coupling reactions catalyzed by transition metals are among the most
      influential in modern synthetic chemistry. The vast majority of transition-metal
      catalyzed cross-couplings rely on a catalytic cycle involving alternating
      oxidation and reduction of the metal center and are generally limited to forging
      just one type of new bond per reaction (e.g., the biaryl linkage formed during a
      Suzuki cross-coupling). This work presents an Isohypsic-Redox Sequence (IRS) that
      uses one metal to effect two catalytic cycles, thereby generating multiple new
      types of bonds from a single catalyst source. We show that the IRS strategy is
      amenable to several widely used transformations including the Suzuki-Miyaura
      coupling, Buchwald-Hartwig amination, and Wacker oxidation. Furthermore, each of
      these reactions generates value-added heterocycles with significant sp3 -C (3
      dimensional) content. Our results provide a general framework for generating
      complex products by using a single metal to fulfill multiple roles. By uniting
      different combinations of reactions in the isohypsic and redox phases of the
      process, this type of catalytic multiple bond-forming platform has the potential
      for wide applicability in the efficient synthesis of functional organic
      molecules.

PMID- 30203870
TI  - Bis-Naphthalene Cleft with Aggregation-Induced Emission Properties through Lone
      Pair???pi Interactions.
AB  - A rigid molecular cleft shows unique aggregation-induced emission (AIE) by
      restricting the motion of aldehyde through intermolecular lone pair???pi
      interactions, which are tuned by side chains. This AIE luminogen was demonstrated
      to work as a fluorescent sensor for aniline and an optical chirality sensor for
      chiral amine.

PMID- 30203871
TI  - Acute reduction of lower-body contractile function following a microbiopsy of m.
      vastus lateralis.
AB  - Twenty-three resistance trained men 18-35 years (23 [3] years, 1.8 [0.1] m, 81
      [10] kg body mass, 2.3 [1.1] years resistance training experience; mean [SD])
      performed repeated maximal voluntary isometric squats (ISQ) and countermovement
      jumps (CMJ) pre- and +30 minutes post a unilateral microbiopsy of m. vastus
      lateralis. ISQ and CMJ were simultaneously measured by two force plates sampling
      ipsilateral (biopsied) and contralateral (non-biopsied) limb force. Bilateral
      limb force (ipsilateral + contralateral) and imbalance (ipsilateral/bilateral)
      data are reported as % change from pre-biopsy (mean [95% CI]). A post-biopsy
      reduction in bilateral ISQ peak force (-17 [-23, -11] %; P < 0.001), ISQ rate of
      force development (RFD; -28 [-41, -15] %, P = 0.002) and CMJ peak take-off force
      (-7 [-13, -1]%, P = 0.019) occurred. Imbalance was observed for ISQ peak force
      (3.2 [2.1, 4.3] %, P < 0.001), RFD (2.8 [1.6, 4.0] %, P < 0.001) and CMJ landing
      (3.3 [1.0, 5.6] %, P = 0.009), resultant of a force transfer from the ipsilateral
      (biopsied) to the contralateral (non-biopsied) limb. These data suggest that in
      young, resistance trained men a modulatory influence on maximal voluntary static
      and dynamic lower-body contractile function is evoked acutely (+30 minutes)
      following a microbiopsy of m. vastus lateralis.

PMID- 30203872
TI  - Xenotransplantation of goat ovary as an alternative to analyse follicles after
      vitrification.
AB  - The aim of this study was to evaluate the caprine preantral follicles enclosed on
      vitrified/warmed ovarian cortex grafted to nude BALB/mice during 1 month. The
      ovarian cortex from goats was fragmented (3 * 3 * 0.5 mm) and divided into four
      groups: fresh control, vitrified control, fresh transplant and vitrified
      transplant. Follicular morphology, development and density, fibrosis as well as
      apoptosis, and tissue revascularization were evaluated. It was also observed a
      significant decrease in morphologically normal preantral (primordial, transition,
      primary and secondary) follicles in both vitrified control and vitrified
      transplant treatments when compared with both fresh control and fresh transplant.
      However, fresh control and fresh transplant exhibited a similar percentage of
      developing follicles. Additionally, Vitrified control showed a significant
      increase in developing follicles in comparison with both fresh control and fresh
      transplant. Follicular density significantly decreased in all treatments in
      comparison with fresh control. We observed high fibrosis in both fresh transplant
      and vitrified transplant. The mRNA expression of caspase 3 was lower in both
      fresh transplant and vitrified transplant in comparison with vitrified control.
      In conclusion, xenotransplantation is an excellent strategy to maintain normal
      preantral follicle morphology after vitrification/warming of goat ovarian tissue.
      Yet, in order to ensure the survival and development of these follicles, it is
      essential to improve the revascularization of the graft.

PMID- 30203873
TI  - Catalyst-Free Hydroboration of CO2 With a Nucleophilic Diborane(4).
AB  - Hydroboration generally requires the presence of a catalyst to lower the barrier
      for hydride transfer. This work reports on the first catalyst-free CO2
      hydroboration with a neutral boron compound, the nucleophilic diborane [HB(hpp)]2
      , 1 (hpp=1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2-a]pyrimidinate). Further
      hydroboration reactions to bis(boryl)acetals are possible. In acetonitrile, but
      not in dichloromethane solutions, hydroboration of a first CO2 is followed by
      hydroboration of a second CO2 molecule. Detailed kinetic measurements for both
      hydroboration steps were carried out and the influence of the solvent and the
      addition of a Lewis base on the rate constants analyzed. In contrast to catalyst
      free hydroboration of CO2 , hydroboration of the less electrophilic acetone
      requires the presence of an activating Lewis acid.

PMID- 30203874
TI  - The Twisted Benzo[ghi]-Perylenetriimide Dimer as a 3D Electron Acceptor for
      Fullerene-Free Organic Photovoltaics.
AB  - A series of twisted N,N-linked benzo[ghi]-perylenetriimide dimers (t-BPTI) with
      various lengths of the alpha-branched alkyl side chain at the six-membered imide
      ring position was designed, synthesized, and characterized. These compounds
      showed the low-lying LUMO energy level of -3.78 eV, which was similar to that of
      PC61 BM (-3.71 eV), but with intensive optical absorption in the range 350-500
      nm. The twisted molecular geometry with two nearly perpendicular BPTI planes
      achieved a favorable nanoscale phase separation by relieving the self-aggregation
      of rigid BPTI units in blend films. The acceptor t-BPTI-3 unit with the longest
      alkyl side chains has been demonstrated to be an efficient electron acceptor in
      solution-processed bulk heterojunction organic photovoltaics (OPV), giving a
      power conversion efficiency of 3.68 % when using conjugated polymer PTB7-Th as
      the donor and without additional treatments.

PMID- 30203875
TI  - Bio-inspired Transition Metal Complexes as Electrocatalysts for Oxygen Reduction
      Reaction.
AB  - The oxygen reduction reaction (ORR) is one of the most important reactions in
      life processes and energy conversion systems. To alleviate global warming and the
      energy crisis, the development of high-performance electrocatalysts for ORR for
      their application in energy conversion and storage devices such as metal-air
      batteries and fuel cells is highly desirable. Inspired by the biological oxygen
      activation/reduction process associated with heme- and multicopper-containing
      metalloenzymes, iron and copper-based transition metal complexes have been
      extensively explored as ORR electrocatalysts. This review outlines recent
      progress on non-precious-metal electrocatalysts for ORR that do not require
      pyrolysis treatment, which is regarded as desirable from the viewpoint of bio
      inspired molecular catalyst design, focusing on iron/cobalt macrocycles
      (porphyrins, phthalocyanines, and corroles) and copper complexes in which the ORR
      activity is tuned by ligand variation/substitution, the method of catalyst
      immobilization, and the underlying supporting materials. Current challenges and
      exciting imminent developments in bio-inspired ORR electrocatalysts are
      summarized and proposed.

PMID- 30203876
TI  - Disruption of Symmetry: A Quantitative Assessment of Facial Skeleton Anatomy in
      Children born with Unilateral Cleft Lip and Palate.
AB  - INTRODUCTION: Unilateral cleft lip and palate (UCLP) is a craniofacial deformity
      characterized by lip and palate clefting on one side of the face. UCLP originates
      from failures in neural crest migration and differentiation during embryological
      development, impairing facial primordia fusion (medial nasal, maxillary, and
      lateral processes) resulting in clefting. Persons with UCLP experience issues in
      nasal breathing, speaking, and mastication. Facial directional asymmetry (DA),
      consisting of left-right side differences biased towards one particular side, can
      arise from environmental or hereditary factors. MATERIALS AND METHODS: This
      retrospective, cross-sectional study, quantifies DA in the facial skeleton of
      children with surgically repaired UCLP. We tested the hypothesis that DA is
      significantly increased in persons with UCLP. Twenty-three anatomical landmark
      coordinates were measured from cone beam computed tomography images of two age-
      and sex-matched samples: 1) persons with UCLP post-surgery (n = 26, 7-17 yrs.);
      2) typical children (n = 26, 7-17 yrs.). From these coordinates, 81 bilateral
      paired measurements were calculated and statistically assessed for DA differences
      using Principal Components Analysis and Euclidean Distance Matrix Analysis.
      RESULTS: Samples separate in high-dimensional space and 35.8% of bilateral
      measures are statistically significant. Patterns of significant DA differences
      between samples were explored based on magnitude. Compared to the control group,
      in all but five cases, significant DA was greater in persons with UCLP.
      CONCLUSIONS: Regions derived from the maxillary and nasal prominences
      demonstrated the most DA. These results are important for medical practitioners
      for identifying the extent to which patients with UCLP deviate from the norm.
      This article is protected by copyright. All rights reserved.

PMID- 30203877
TI  - The role of the vagus nerve in appetite control: Implications for the
      pathogenesis of obesity.
AB  - The communication between the gut and the brain is important for the control of
      energy homeostasis. In response to food intake, enteroendocrine cells secrete gut
      hormones, which ultimately suppress appetite through centrally-mediated
      processes. Increasing evidence implicates the vagus nerve as an important conduit
      in transmitting these signals from the gastrointestinal tract to the brain.
      Studies have demonstrated that many of the gut hormones secreted from
      enteroendocrine cells signal through the vagus nerve, and the sensitivity of the
      vagus to these signals is regulated by feeding status. Furthermore, evidence
      suggests that a reduction in the ability of the vagus nerve to respond to the
      switch between a "fasted" and "fed" state, retaining sensitivity to orexigenic
      signals when fed or a reduced ability to respond to satiety hormones, may
      contribute to obesity. This review draws together the evidence that the vagus
      nerve is a crucial component of appetite regulation via the gut-brain axis, with
      a particular emphasis on experimental techniques and future developments.

PMID- 30203880
TI  - Abstracts of the 24th Congress of the European Sleep Research Society, 25-28
      September 2018, Basel, Switzerland.

PMID- 30203881
TI  - Evaluation of the delivery of long-term at-home nursing care: An example of good
      practice.
AB  - AIMS AND OBJECTIVES: To evaluate the influence of long-term at-home nursing care
      (LTHNC) on patient functional status. The specific aims were as follows: (1) to
      analyse the influence of LTHNC on patient functional status in terms of
      activities of daily living; (2) to evaluate the risk of pressure sores and
      pressure sore prevention in patients receiving LTHNC. BACKGROUND: LTHNC is a form
      of care for chronically ill persons staying at home who do not need
      hospitalisation, but due to their health problems they require regular nursing
      care that can be provided at home. DESIGN: A retrospective descriptive study.
      METHODS: A document research method was used. We collected data from the medical
      records of 1,058 patients receiving LTHNC at the Non-Public Health Care Centre
      OMNI-MED in Bialystok (Poland) for the years 2005-2012. RESULTS: Detailed
      analysis of scores on the Barthel Activities of Daily Living Index revealed
      significant improvement in patient functional status as a result of LTHNC. In
      patients aged 65-80, the Barthel score increased by 8.83 points, and in patients
      aged 64 years and younger, the score increased by 6.58 points (p < 0.001). In the
      oldest patients (>80 years), functional status improved the least, gaining a mean
      of 4.97 points on the Barthel scale. Overall, the demonstrated improvement of
      patient functional status and reduced risk of pressure sore development provide
      evidence that LTHNC is an effective form of care for elderly and chronically ill
      persons staying at home. CONCLUSION: The findings of our study represent a
      positive example of the way good nursing care can benefit patients while
      promoting the autonomous nature of nursing. RELEVANCE TO CLINICAL PRACTICE: The
      results add to our understanding of the functioning of LTHNC by providing
      relevant scientific evidence which may contribute to the development of community
      nursing.

PMID- 30203878
TI  - Mitogen-activated protein kinases MPK4 and MPK12 are key components mediating CO2
      -induced stomatal movements.
AB  - Respiration in leaves and the continued elevation in the atmospheric CO2
      concentration cause CO2 -mediated reduction in stomatal pore apertures. Several
      mutants have been isolated for which stomatal responses to both abscisic acid
      (ABA) and CO2 are simultaneously defective. However, there are only few mutations
      that impair the stomatal response to elevated CO2 , but not to ABA. Such mutants
      are invaluable in unraveling the molecular mechanisms of early CO2 signal
      transduction in guard cells. Recently, mutations in the mitogen-activated protein
      (MAP) kinase, MPK12, have been shown to partially impair CO2 -induced stomatal
      closure. Here, we show that mpk12 plants, in which MPK4 is stably silenced
      specifically in guard cells (mpk12 mpk4GC homozygous double-mutants), completely
      lack CO2 -induced stomatal responses and have impaired activation of guard cell S
      type anion channels in response to elevated CO2 /bicarbonate. However, ABA
      induced stomatal closure, S-type anion channel activation and ABA-induced marker
      gene expression remain intact in the mpk12 mpk4GC double-mutants. These findings
      suggest that MPK12 and MPK4 act very early in CO2 signaling, upstream of, or
      parallel to the convergence of CO2 and ABA signal transduction. The activities of
      MPK4 and MPK12 protein kinases were not directly modulated by CO2 /bicarbonate in
      vitro, suggesting that they are not direct CO2 /bicarbonate sensors. Further data
      indicate that MPK4 and MPK12 have distinguishable roles in Arabidopsis and that
      the previously suggested role of RHC1 in stomatal CO2 signaling is minor, whereas
      MPK4 and MPK12 act as key components of early stomatal CO2 signal transduction.

PMID- 30203879
TI  - Suppression of Arabidopsis GGLT1 affects growth by reducing the L-galactose
      content and borate cross-linking of rhamnogalacturonan-II.
AB  - Boron is a micronutrient that is required for the normal growth and development
      of vascular plants, but its precise functions remain a subject of debate. One
      established role for boron is in the cell wall where it forms a diester cross
      link between two monomers of the low-abundance pectic polysaccharide
      rhamnogalacturonan-II (RG-II). The inability of RG-II to properly assemble into a
      dimer results in the formation of cell walls with abnormal biochemical and
      biomechanical properties and has a severe impact on plant productivity. Here we
      describe the effects on RG-II structure and cross-linking and on the growth of
      plants in which the expression of a GDP-sugar transporter (GONST3/GGLT1) has been
      reduced. In the GGLT1-silenced plants the amount of L-galactose in side-chain A
      of RG-II is reduced by up to 50%. This leads to a reduction in the extent of RG
      II cross-linking in the cell walls as well as a reduction in the stability of the
      dimer in the presence of calcium chelators. The silenced plants have a dwarf
      phenotype, which is rescued by growth in the presence of increased amounts of
      boric acid. Similar to the mur1 mutant, which also disrupts RG-II cross-linking,
      GGLT1-silenced plants display a loss of cell wall integrity under salt stress. We
      conclude that GGLT1 is probably the primary Golgi GDP-L-galactose transporter,
      and provides GDP-L-galactose for RG-II biosynthesis. We propose that the L
      galactose residue is critical for RG-II dimerization and for the stability of the
      borate cross-link.

PMID- 30203882
TI  - Burnout amongst clinical and counselling psychologist: The role of early
      maladaptive schemas and coping modes as vulnerability factors.
AB  - Psychologists are subject to multiple competing emotional demands that increase
      the risk of burnout. Research has demonstrated that burnout arises from both
      organizational and personal factors, including psychologists' personal beliefs
      and coping. Preliminary research indicates that early maladaptive schemas (EMS)
      are associated with high burnout, yet, to date, the role of EMS and associated
      coping responses (maladaptive coping modes [MCM]) in predicting high burnout
      amongst psychologists has not been investigated. Four hundred forty-three
      psychologists completed a self-report online questionnaire comprising the Maslach
      Burnout Inventory-emotional exhaustion scale (EE), Young Schema Questionnaire,
      and Schema Mode Inventory. The two most common EMS amongst psychologists were
      unrelenting standards and self-sacrifice. There was substantial indication of
      burnout, with 18.3% in the high range and 29.6% in the moderate range of EE. The
      most common MCM were detached protector and detached self-soother. Controlling
      for demographics and job demands, EMS accounted for an additional 18% variance in
      EE. MCM accounted for an additional 6% beyond the variance explained by
      demographics, job demands, and EMS. Practical recommendations are suggested to
      reduce psychologist burnout.

PMID- 30203883
TI  - Meaning in life among adolescents: Factorial invariance of the purpose in life
      test and buffering effect on the relationship between emotional dysregulation and
      hopelessness.
AB  - OBJECTIVE: The purpose of the present study was threefold: first, to analyse the
      psychometric properties of a 10-item Spanish version of the Purpose in Life Test,
      which assesses meaning in life (MiL), in a sample of community adolescents;
      second, to analyse the differences between the age and gender groups; and third,
      to analyse whether MiL buffers the relationship between emotional dysregulation
      and hopelessness. METHOD: Participants were 1,599 adolescents from 12 to 19 years
      old, M = 15.69, SD = 2.14. The Purpose in Life Test-10 Items, the Beck
      Hopelessness Scale, and the Difficulties in Emotional Regulation Scale were used.
      RESULTS: A nine-item version showed good fit, psychometric properties (internal
      consistency, construct, and concurrent validity), and factorial invariance across
      gender and age (12-15 years/16-19 years). Difference in MiL between boys and
      girls was not significant, whereas between age groups was significant. MiL had a
      strong buffering effect on the relationship between emotional dysregulation and
      hopelessness. DISCUSSION: It is desirable to promote the sense of MiL in
      adolescents. MiL plays a significant and strong mediator role in the relationship
      between emotional dysregulation and hopelessness, reinforcing the positive role
      of MiL in mental health and as a resource for facing adversity.

PMID- 30203884
TI  - Sexual dysfunction and reproductive concerns in young women with breast cancer:
      Type, prevalence, and predictors of problems.
AB  - OBJECTIVE: A dearth of studies focusing on young women (<40 years) with breast
      cancer have hampered the understanding of the type, prevalence, and predictors of
      sexual dysfunction and reproductive concerns in this population. METHODS: Data
      were collected from 181 women (response rate = 60%) diagnosed with breast cancer
      approximately 2 years previously (age 21-39) using the Swedish National Quality
      Registry for Breast Cancer and a survey including standardized measures of sexual
      dysfunction, reproductive concerns, body image, and health-related quality of
      life. Multivariable logistic binary regression analyses were used to identify
      predictors of sexual dysfunction and reproductive concerns. RESULTS: Sexual
      dysfunction in at least one domain was reported by 68% of the women, and a high
      level of reproductive concerns in at least one dimension was reported by 58%.
      Model results showed that current endocrine treatment was a significant predictor
      of dysfunction related to lubrication (OR 3.8, 95% CI 1.2-12.1) and vaginal
      discomfort (OR 8.7, 95% CI 1.5-51.5). Negative body image was related to
      satisfaction with sex life (OR 1.1, 95% CI 1.0-1.2). A high level of reproductive
      concerns was predicted by a wish for (additional) children in the future (OR 3.4,
      95% CI 1.1-10.2) and by previous chemotherapy (OR 2.5, 95% CI 1.1-5.9).
      CONCLUSIONS: Sexual dysfunction and reproductive concerns are common in young
      women with breast cancer. Current endocrine treatment, previous chemotherapy, a
      negative body image, and a wish for children in the future predict higher level
      of problems.

PMID- 30203885
TI  - Driving cognitions, rumination, and posttraumatic stress disorder in road traffic
      accidents survivors.
AB  - This study evaluated the relationships between driving cognitions (i.e., panic
      related cognitions, accident-related cognitions, and social-related cognitions),
      rumination, and posttraumatic stress disorder (PTSD) symptoms in a sample of road
      traffic accidents (RTAs) survivors. We also investigated the indirect effect of
      driving cognitions on PTSD symptoms through rumination. The sample included 633
      drivers (62% were men; Mage = 36.09; standard deviation [SD] = 11.42 years). The
      participants completed scales measuring driving cognitions, rumination, and PTSD
      symptoms, as well as providing their demographic information. The results showed
      that all three types of driving cognitions assessed in the present study and
      rumination were significantly positively associated with PTSD symptoms.
      Furthermore, rumination mediated the relation between social-related cognitions
      and PTSD symptoms. The implications for PTSD treatment and future research are
      discussed.

PMID- 30203886
TI  - Self-practice/self-reflection as an alternative to personal training-therapy in
      cognitive behavioural therapy training: A qualitative analysis.
AB  - INTRODUCTION: The study examined the qualitative impact and credibility of self
      practice/self-reflection (SP/SR). METHODS: Nineteen participants reflected on the
      self-practice of cognitive behavioural therapy techniques. Written reflections
      were analysed using inductive thematic analysis. RESULTS: Two superordinate
      themes (a) Personal-self and (b) Therapist-self, with themes and subthemes
      emerged. CONCLUSION: The themes found equivalents in existing goals of
      traditional therapists' training-therapy. Though brief, SP/SR may be a credible
      alternative/adjunctive training-therapy.

PMID- 30203887
TI  - Inhibition of microRNA-143-3p attenuates myocardial hypertrophy by inhibiting
      inflammatory response.
AB  - MicroRNA-143-3p (miR-143-3p) is involved in the initiation of inflammatory
      response and the progression of cardiovascular diseases. Myocardial hypertrophy
      is a common symptom in numerous cardiovascular diseases. In the current study, we
      attempted to demonstrate the role of miR-143-3p in the development of myocardial
      hypertrophy by focusing on its association with inflammation. Myocardial
      hypertrophy was induced by transverse aortic constriction (TAC) method in vivo
      and by H2 O2 administration in vitro. The expression status of miR-143-3p and
      downstream effectors were detected in animal heart tissues and H9c2 cells.
      Furthermore, the effect of miR-143-3p inhibition on H2 O2 -induced changes in
      ERK5/PPARdelta/NF-kappaB axis was assessed. TAC induced oxidative stress and
      inflammation in rat heart tissues, which was associated with the increased
      expressions of miR-143-3p and p-ERK5. However, the up-regulated expression of miR
      143-3p had no effect on the expression of ERK5, which was a direct target of miR
      143-3p. The results of in vitro assays showed that H2 O2 administration increased
      the levels of miR-143-3p and p-EKR5 and induced the activation of NF-kappaB
      pathway. After the inhibition of miR-143-3p, the activation of EKR5 and NF-kappaB
      pathway was suppressed, whereas the expression of PPARdelta was up-regulated. The
      current study demonstrated that miR-143-3p is crucial to the initiation of
      inflammatory response induced by myocardial hypertrophy. The activation of ERK5
      following miR-143-3p up-regulation appears to be a complementary response to
      induce the subsequent anti-inflammatory signaling transduction, which needed
      further exploration.

PMID- 30203888
TI  - Quercetin preferentially induces apoptosis in KRAS-mutant colorectal cancer cells
      via JNK signaling pathways.
AB  - Colorectal cancer (CRC) is the third most common type of cancer, and its
      incidence and mortality are markedly increasing worldwide. Oncogenic mutations of
      KRAS occur in up to 40% of CRC cases and pose a great challenge in the treatment
      of the disease. Quercetin is a dietary flavonoid that exerts anti-oxidant, anti
      inflammatory and anti-cancer properties. The current study investigated the anti
      proliferative effect of quercetin on CRC cells harboring mutant or wild-type
      KRAS. The effect of quercetin on cell viability was investigated by MTT and
      colony formation assays, and apoptosis was detected using flow cytometry by
      labeling cells with Annexin V-FITC. The expression of the relevant proteins was
      examined by western blotting. The data revealed that KRAS-mutant cells were more
      sensitive to quercetin-induced apoptosis than wild-type cells. Caspase activation
      was involved in quercetin-induced apoptosis. In addition, quercetin selectively
      activated the c-Jun N-terminal kinase (JNK) pathway in KRAS-mutant cells, while
      inhibition of phospho-JNK by SP600125 blocked quercetin-induced apoptosis. The
      results of the present study suggest that treatment with quercetin, a common
      flavonoid in plants, is potentially a useful strategy for the treatment of CRCs
      carrying KRAS mutations.

PMID- 30203889
TI  - 3D ultrashort echo time MRI of the lung using stack-of-spirals and spherical k
      Space coverages: Evaluation in healthy volunteers and parenchymal diseases.
AB  - BACKGROUND: Ultrashort echo time (UTE) has been shown to improve lung MRI quality
      in three dimensions. The evaluation of 3D-UTE stack-of-spirals VIBE (3D-USV)
      sequence for parenchymal diseases and a comparison of performance with that of a
      spherical mode of acquisition is needed. PURPOSE: To assess MRI quality using a
      prototypical 3D-USV sequence and to compare performance with that of a spherical
      acquisition using Pointwise Encoding Time Reduction with Radial Acquisition
      (PETRA). STUDY TYPE: Monocenter, prospective. POPULATION: Twelve healthy
      volunteers and 32 adult patients with either cystic fibrosis (CF; n = 16) or
      interstitial lung disease (ILD; n = 16). FIELD STRENGTH/SEQUENCE: Both free
      breathing 3D-USV and PETRA were completed at 1.5T. ASSESSMENT: In healthy
      volunteers, visual analysis of imaging quality was scored using a Likert scale.
      Quantitative evaluation of apparent signal ratio (Sr) and contrast ratio (Cr) was
      measured. Patients with CF and ILD completed both computed tomography (CT) and
      MRI. Depiction of structural alterations was assessed using dedicated clinical
      scores. All evaluations were done in consensus by two readers. STATISTICAL TESTS:
      Comparison of means was assessed using the Wilcoxon signed rank test. Concordance
      and agreement between CT and MRI were assessed using the intraclass correlation
      coefficient (ICC) and kappa test. RESULTS: In controls, 3D-USV yielded lower
      artifacts owing to better automatic respiratory synchronization than PETRA (P <
      0.001). However, Sr and Cr of 3D-USV were found significantly lower by 2.25- and
      2.36-fold, respectively (P < 0.001). In patients, 3D-USV and PETRA showed
      comparable performances to assess airway severity in CF (Bhalla score, ICC = 0.89
      and ICC = 0.92, respectively) and presence of structural alterations in ILD such
      as honeycombing (kappa = 0.68 and kappa = 0.69, respectively). DATA CONCLUSION:
      3D-USV enables high-resolution morphological imaging of the lung without need of
      an external device to compensate respiratory motions. Automation and robustness
      of the method may facilitate clinical application for both airway and
      interstitial lung investigations. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage
      1 J. Magn. Reson. Imaging 2018;48:1489-1497.

PMID- 30203890
TI  - Using the primary process emotional-behavioural system to better meet patient
      needs in psychotherapy.
AB  - In order to increase therapeutic impact by enhancing awareness of clients'
      nonverbal communications, this article operationalizes the therapeutic alliance
      as a needs-satisfaction process. The client's competence as a needs seeker and
      the therapist assisting with the client's expression and satiation of basic
      social needs are proposed as being key mechanisms of change. Functional model of
      primary emotions derived from Panksepp's seven primary emotional systems (care
      seeking, caretaking, lust, fear and anxiety, anger, play, seeking, plus dominance
      and disgust) is integrated with Functional Analytic Psychotherapy's emphasis on
      in-session contingent natural reinforcement of clients' target behaviours. By
      identifying in-the-moment cues of underlying emotional-behavioural functions
      drawn from a categorization of clients' nonverbal communication can bridge the
      gap between client private events and therapist observables, in order to maximize
      therapist attunement and responsiveness to clients, and to increase the
      effectiveness of clinical interventions.

PMID- 30203891
TI  - A Preview of Selected Articles - October 2018.

PMID- 30203892
TI  - Aberrant structural-functional coupling in adult cannabis users.
AB  - Cellular studies indicate that endocannabinoid type-1 retrograde signaling plays
      a major role in synaptic plasticity. Disruption of these processes by delta-9
      tetrahydrocannabinol (THC) could produce alterations either in structural and
      functional brain connectivity or in their association in cannabis (CB) users.
      Graph theoretic structural and functional networks were generated with diffusion
      tensor imaging and resting-state functional imaging in 37 current CB users and 31
      healthy non-users. The primary outcome measures were coupling between structural
      and functional connectivity, global network characteristics, association between
      the coupling and network properties, and measures of rich-club organization.
      Structural-functional (SC-FC) coupling was globally preserved showing a positive
      association in current CB users. However, the users had disrupted associations
      between SC-FC coupling and network topological characteristics, most perturbed
      for shorter connections implying region-specific disruption by CB use. Rich-club
      analysis revealed impaired SC-FC coupling in the hippocampus and caudate of
      users. This study provides evidence of the abnormal SC-FC association in CB
      users. The effect was predominant in shorter connections of the brain network,
      suggesting that the impact of CB use or predispositional factors may be most
      apparent in local interconnections. Notably, the hippocampus and caudate
      specifically showed aberrant structural and functional coupling. These structures
      have high CB1 receptor density and may also be associated with changes in
      learning and habit formation that occur with chronic cannabis use.

PMID- 30203894
TI  - Telomere length, telomerase reverse transcriptase promoter mutations, and
      melanoma risk.
AB  - Telomere repeats at chromosomal ends, critical for genomic integrity, undergo age
      dependent attrition and telomere length has been associated with different
      disorders including cancers. In this study, based on 1469 patients and 1158
      healthy controls, we show a statistically significant (P = 6 * 10-10 )
      association between increased telomere length and melanoma risk. Mendelian
      randomization, using 5 telomere length-associated polymorphisms, ruled out
      confounding factors or reverse causality and showed association between increased
      telomere length and melanoma risk with odds ratio of 2.66 (95% confidence
      interval: 2.07-3.25). Age-dependent telomere attrition was faster in melanoma
      cases than controls (P = .01). The carriers of a highly penetrant germline -57A>C
      TERT promoter mutation, in a previously reported melanoma family, had longer
      telomeres than the noncarriers. The mutation causes increased TERT and telomerase
      levels through creation of a binding motif for E-twenty six (ETS) transcription
      factors and the carriers develop melanoma with an early age of onset and rapid
      progression to metastasis. In analogy, we hypothesize that increased telomere
      length in melanoma patients reflects stochastic increased telomerase levels due
      to common genetic variation. Paradoxically, we observed shorter telomeres (P = 1
      * 10-5 ) in primary tumors from unrelated melanoma patients with (121) than
      without (170) somatic TERT promoter mutations that similar to the germline
      mutation, also create binding motifs for ETS transcription factors. However, the
      age-dependent telomere attrition was faster in tumors with the TERT promoter
      mutations than in those without such mutations. Besides a robust association
      between increased telomere length and risk, our data show a perturbed telomere
      homeostasis in melanoma.

PMID- 30203893
TI  - Mutational and cytogenetic analyses of 188 CLL patients with trisomy 12: A
      retrospective study from the French Innovative Leukemia Organization (FILO)
      working group.
AB  - Trisomy 12 (tri12) is the second most frequent chromosomal aberration (15%-20%)
      in chronic lymphocytic leukemia (CLL). Tri12 confers an intermediate prognosis
      but is a heterogeneous entity. We examined whether additional mutational or
      chromosomal alterations might impact tri12 patient outcomes. This retrospective
      study, carried out by the French Innovative Leukemia Organization, included 188
      tri12 patients with comprehensive information on immunoglobulin heavy chain
      (IGHV) gene status, karyotypic/FISH abnormalities, and NOTCH1, TP53, SF3B1, and
      MYD88 mutations. The main cytogenetic abnormalities associated with tri12 were
      del(13q) (25%), additional trisomies (14%) (including tri19 (10%) and tri18
      (4%)), 14q32 translocations (10%), del(17p) (6.5%), del(14q) (4%), and del(11q)
      (4%). Unmutated (UM) IGHV, NOTCH1, and TP53, mutations were identified in
      respectively 66%, 25%, and 8.5% of cases. Multivariate analyses showed that
      additional trisomies (HR = 0.43, 95% CI = 0.23-0.78, P = .01) were associated
      with a significantly longer time to first treatment in Binet stage A patients and
      with a lower risk of relapse (HR = 0.37, 95% CI = 0.15-0.9, P = .03) in the
      overall tri12 population. Binet stage B/C, TP53 disruption, and UM IGHV status
      were associated with a shorter time to next treatment, while Binet stage B/C (HR
      = 4, 95% CI = 1.6-4.9, P = .002) and TP53 disruption (HR = 5, 95% CI = 1.94
      12.66, P = .001) conferred shorter overall survival in multivariate comparisons.
      These data indicate that additional cytogenetic and mutational abnormalities, and
      particularly additional trisomies, IGHV status, and TP53 disruption, influence
      tri12 patient outcomes and could improve risk stratification in this population.

PMID- 30203895
TI  - Interactions of ethanol and caffeine on apoptosis in the rat cerebellum
      (voluntary ethanol consumers).
AB  - Ethanol alters motricity, learning, cognition, and cellular metabolism in the
      cerebellum. The combination of ethanol with caffeine by consuming "energy drinks"
      is becoming increasingly popular among young people. We analyzed the use of
      ethanol and caffeine on apoptosis in the cerebellum of UChB rats. The adult rats
      were divided into three groups (n = 14/group): UChB group: rats fed with 1:10
      (v/v) ethanol ad libitum (free choice for water or ethanol) drinking from >1.9 mL
      of ethanol/kg body weight/day, Control group and UChB/caffeine group (free choice
      for water or ethanol + caffeine 300 mg/L). The treatments occurred from Day 100
      till Day 150, totalizing 50 days of ethanol/caffeine ingestion. Cerebellar
      sections were subjected to immunohistochemistry and gene expression for Real Time
      PCR (RT-PCR) for Caspase-3, XIAP, and insulin-like growth factor 1-receptor (IGF
      1R). The results showed a significant increase in the gene expression of Caspase
      3 and XIAP in UChB group. On the other hand, the animals of the UChB/caffeine
      group showed similar results to the Controls. Regarding IGFR-1, there was greater
      expression in the UChB groups with strong labeling in Purkinje cells. Ethanol
      produces neuronal and glial neurodegeneration on the cerebellum of UChB rats. The
      simultaneous ingestion of ethanol and caffeine reversed the ethanol damages
      acting caffeine with a neuroprotective effect.

PMID- 30203896
TI  - Improved cytogenetic characterization and risk stratification of pediatric acute
      lymphoblastic leukemia using single nucleotide polymorphism array analysis: A
      single center experience of 296 cases.
AB  - Single nucleotide polymorphism array (SNP-A) analyses are increasingly being
      introduced in routine genetic diagnostics of acute lymphoblastic leukemia (ALL).
      Despite this, only few studies that have compared the diagnostic value of SNP-A
      with conventional chromosome banding have been published. We here report such a
      comparison of 296 ALL cases, the largest series to date. Only genomic imbalances
      >5 Mb and microdeletions targeting the BTG1, CDKN2A/B, EBF1, ERG, ETV6, IKZF1,
      PAX5, and RB1 genes and the pseudoautosomal region 1 (PAR1) were ascertained, in
      agreement with recent guidelines. Of 36 T-cell ALL cases, the karyotypes of 24
      cases (67%) were revised by SNP-A analyses that either revealed additional
      imbalances >5 Mb or better characterized the changes found by G-banding. Of 260 B
      cell precursor (BCP) ALL cases, SNP-A analyses identified additional copy number
      alterations, including the above-mentioned microdeletions, or better
      characterized the imbalances found by G-banding in 236 (91%) cases. Furthermore,
      the cytogenetic subtype classification of 41/260 (16%) BCP ALL cases was revised
      based on the SNP-A findings. Of the subtype revisions, 12/41 (29%) had clinical
      implications as regards risk stratifying cytogenetic groups or genotype-specific
      minimal residual disease stratification. We conclude that SNP-A analyses
      dramatically improve the cytogenetic characterization of both T-cell and BCP ALL
      and also provide important information pertinent to risk stratification of BCP
      ALL.

PMID- 30203897
TI  - Evaluation of ovarian and metabolic effects of GnRH modulators in two rat models
      of polycystic ovary syndrome.
AB  - Gonadotropin-releasing hormone (GnRH) modulators are widely used in numerous
      reproductive conditions including infertility. Several clinical studies showed
      mixed results regarding the efficacy of GnRH modulators in patients with
      polycystic ovary syndrome (PCOS). Along with this, few preclinical studies focus
      on the effect of GnRH modulators in PCOS-induced animals. Therefore, the present
      study was designed to study the effect of leuprolide and cetrorelix on hormonal,
      metabolic, and menstrual dysfunction PCOS rats. Prepubertal female rats were
      divided into four groups: Group I received a normal pellet diet and Groups II,
      III, and IV received 40% high-fat diet for 105 days. Similarly, adult female rats
      were divided into four groups: Group I received 1% carboxymethylcellulose (CMC)
      and Groups II, III, and IV received letrozole (1 mg/kg, per oral [p.o.] in 1%
      CMC) for 21 days. Thereafter, leuprolide (2.5 ug/rat, s.c.) and cetrorelix (10
      ug/kg, subcutaneous [s.c.]) treatment were given to Group III and Group IV
      animals, respectively, for 21 days. Oral glucose tolerance test, lipid profile,
      fasting glucose, insulin, estrus cycle, hormonal profile, ovary weight, ovarian
      histopathological changes, and LHR and FSHR expressions were measured. Treatment
      with leuprolide and cetrorelix did not improve glucose intolerance, insulin
      level, insulin sensitivity indices, sex hormone levels, lipid profile, and estrus
      cycle. Only testosterone level, total cholesterol level, and follicular
      development were improved. Therefore, it was concluded that both leuprolide and
      cetrorelix showed improvement in follicular development, which could be helpful
      for improving fertility in PCOS.

PMID- 30203898
TI  - Morphological Redescription and Molecular Identification of Trichodina reticulata
      Hirschmann & Partsch, 1955 (Ciliophora, Mobilida, Trichodinidae) with the
      Supplemental New Data of SSU rDNA and ITS-5.8S rDNA.
AB  - During a survey of trichodinids in Chongqing, China, two populations of
      Trichodina reticulata Hirschmann & Partsch, 1955 were isolated from gills of the
      freshwater fishes, Carassius auratus and Ctenopharyngodon idellus, and 11
      molecular samples containing small subunit (SSU) rDNA and internal transcribed
      spacer (ITS)-5.8S rDNA were newly sequenced. Both populations fell within the
      range of morphometry and corresponded well with the diagnostic morphological
      features of Trichodina reticulata Hirschmann & Partsch, 1955. It should be noted
      that one population possessed obvious central granules in the adhesive disc,
      while the other one did not. The detailed morphological redescription for these
      two populations is given in this work. Although some intraspecific differences
      were found, both populations were confirmed as Trichodina reticulata based on the
      morphological study and molecular data, including the sequence analysis of the
      primary and secondary structures of SSU rDNA, genetic distances and phylogenetic
      tree. Our study supports the assertion that central granules in the adhesive disc
      might be an auxiliary feature rather than a heritable character for determining
      taxonomic affiliations among trichodinids.

PMID- 30203899
TI  - Oral leukoplakia: A diagnostic challenge for clinicians and pathologists.

PMID- 30203900
TI  - Toxoplasma gondii, Neospora caninum and Encephalitozoon cuniculi in Animals from
      Captivity (Zoo and Circus Animals).
AB  - Problems with parasitic infections are common in zoological gardens and circuses.
      In some animals it can lead to several disorders such as systemic disease,
      reproductive disorders (abortions and neonatal mortality), and even to death if
      severe illness is untreated. Thus, the aim of this study was to evaluate the
      prevalence of three common parasites in 74 animals from three zoos, and four
      circuses in Southern Italy. Antibodies to Toxoplasma gondii, Neospora caninum,
      and Encephalitozoon cuniculi were detected in 51%, 12%, and 20% of animals,
      respectively. Co-infections of T. gondii and N. caninum were reported in seven
      animals (9%) and co-infection of T. gondii and E. cuniculi in one animal. T.
      gondii, N. caninum and E. cuniculi seroprevalence differed in type of diet (P <=
      0.0001; P <= 0.037 and P <= 0.004, respectively). T. gondii and E. cuniculi
      seroprevalence also differed in animal families (P <= 0.0001) and according to
      type of housing (P <= 0.003), respectively. Statistical differences were not
      found in other characteristics (gender, age, country of birth, origin, and
      contact with cats or dogs). This is the first serological study focusing on
      protozoan and microsporidian parasites in zoo and circus animals from Southern
      Italy and the first detection of antibodies to E. cuniculi in camels in Europe.

PMID- 30203901
TI  - Systemic immune-inflammation index could estimate the cross-sectional high
      activity and the poor outcomes in immunosuppressive drug-naive patients with ANCA
      associated vasculitis.
AB  - OBJECTIVES: We investigated whether systemic immune-inflammation index (SII) at
      diagnosis can estimate the cross-sectional high activity and predict the poor
      outcomes in immunosuppressive drug-naive patients with ANCA-associated vasculitis
      (AAV). METHODS: We retrospectively reviewed the medical records of 163 patients
      with AAV and obtained clinical and laboratory data. We calculated Birmingham
      vasculitis activity score (BVAS) as well as five factor score (FFS) (2009) at
      diagnosis. SII at diagnosis was calculated by the equation of [SII at diagnosis =
      platelet count x neutrophil count / lymphocyte count at diagnosis]. Severe AAV
      was defined as BVAS at diagnosis >= 16. The odds ratio (OR) was assessed using
      the multivariable logistic regression analysis and cumulative survival rates were
      compared by the Kaplan-Meier survival analysis. RESULTS: The median age at
      diagnosis was 58.0 years old and 51 patients were men. The median BVAS was 12.0.
      Fifty-seven patients had severe AAV. The median SII at diagnosis was 1,349.6. In
      the multivariable analysis, only SII exhibited a significant OR for the cross
      sectional severe AAV (P = 0.043). We obtained the cut-off of SII at diagnosis for
      severe AAV as 1,573.56. Patients with SII at diagnosis >= 1,573.56 exhibited a
      significantly high relative risk (RR) of the cross-sectional severe AAV compared
      to those without (RR 4.625). Furthermore, patients with SII at diagnosis >=
      1,573.56 exhibited significantly the lower cumulative relapse free and renal
      survivals than those without. CONCLUSION: SII at diagnosis could estimate the
      cross-section severe AAV and predict the poor outcomes in AAV patients. This
      article is protected by copyright. All rights reserved.

PMID- 30203902
TI  - Lichen planus and diabetes mellitus: Systematic review and meta-analysis.
AB  - OBJECTIVE: The aim of this study was to perform a systematic review and meta
      analysis answering the following questions: (a) "What is the prevalence and risk
      of oral lichen planus among patients with diabetes mellitus?" and (b) "What is
      the prevalence and risk of diabetes mellitus among patients with oral lichen
      planus?". MATERIAL AND METHODS: A bibliographic search was conducted in
      PubMed/Medline and Scopus database from 1966 to March 2018, using the following
      terms: "Lichen planus" AND "Diabetes mellitus" AND "Prevalence" AND "Oral mucosal
      lesions". RESULTS: Twenty-two studies were included in this review. Twelve
      studies assessed the prevalence of diabetes mellitus among patients with lichen
      planus. The prevalence reported ranges from 1.6% to 37.7% with a relative risk of
      2.432. Ten studies assessed the prevalence of lichen planus among patients with
      diabetes mellitus which showed a prevalence of lichen planus ranging from 0.5% to
      6.1% with a relative risk of 1.4. CONCLUSIONS: Contradictory results were found
      when analyzing the relationship between lichen planus and diabetes mellitus.
      Diverse factors should be considered when studying this association for a correct
      interpretation of results. Diabetes mellitus has high prevalence and morbidity,
      which is why new case-control studies are needed to further investigate this
      association.

PMID- 30203903
TI  - Liver transplantation for Hepatitis-B-associated liver disease - Three decades of
      experience.
AB  - BACKGROUND: Hepatitis B (HBV)-associated end-stage liver disease used to be a
      relevant indication for liver transplantation (LT). After transplantation, HBV
      reinfection remains a serious issue. Different strategies to prevent HBV
      reinfection range from the single application of immunoglobulins (HBIG), to the
      use of modern nucleoside/nucleotide analogues (NUC) in combination with HBIG,
      followed by HBIG-discontinuation. The aim of this analysis was to compare
      different strategies and to sum up the results of 30 years at a high-volume
      transplant center and deliver additional information on the histopathological
      level. METHODS: Data of 372 liver transplantations performed for the HBV-induced
      liver disease in 352 patients were extracted from a prospectively organized
      database. HBV-reinfection was determined in the entire cohort, according to the
      mode of HBV-prophylaxis. Differences in survival rates were analyzed in patients
      with successful prophylaxis, untreated and controlled HBV-reinfection.
      Histopathological results were obtained from protocol biopsies in 151 patients.
      RESULTS: HBV-reinfection was significantly associated with the type of
      prophylaxis, presence of HBs-Antigen at the moment of LT, transplant year and
      influencing the overall survival before 2005. After the introduction of modern
      NUCs, HBV-reinfection stopped to impact HBV-associated transplant loss and
      survival. Controlled HBV-infection prevents from HBV-associated transplant
      hepatitis and fibrosis development. The role of HBIG declines in favor of NUCs.
      CONCLUSIONS: Uncontrolled HBV-reinfection does not occur any more. Even in the
      presence of Hbs-antigen, transplant fibrosis does not develop. The most reliable
      mode to prevent HBV-recurrence remains the combination of NUCs with a high
      genetic barrier and HBIG. However, HBIG can safely be discontinued after LT.

PMID- 30203904
TI  - Double lung transplantation in an HIV-positive patient with Mycobacterium
      kansasii infection.
AB  - Good outcomes with kidney and liver transplantation in HIV-positive patients have
      led clinicians to recommend lung transplantation in HIV-positive patients based
      on extrapolated data. Pre-transplant mycobacterial infection is associated with
      an increased risk of developing new infection or aggravating existing infection,
      though it does not contraindicate transplantation in non-HIV-infected patients.
      However, no data exists regarding the outcome of HIV-positive patients with pre
      transplant mycobacterial infection. We report a case of double lung
      transplantation in a 50-year-old HIV-positive patient with alpha-1 antitrypsin
      deficiency. Prior to transplantation, Mycobacterium kansasii was isolated in one
      sputum culture and the patient was considered merely colonized as no clinical
      evidence of pulmonary or disseminated disease was present. The patient
      successfully underwent a double lung transplantation. Nontuberculous
      mycobacterial infection was diagnosed histologically on examination of native
      lungs. Surveillance and watchful waiting were chosen over treatment of the
      infection. HIV remained under control post-transplantation with no AIDS-defining
      illnesses throughout the follow-up. A minimal acute rejection that responded to
      increased corticosteroids was reported. At 12 months post-transplant, a
      bronchiolitis obliterans syndrome was diagnosed after a drop in FEV1. No evidence
      of isolation nor recurrence of nontuberculous mycobacteria was reported post
      transplantation. At 15 months post-transplant, the patient remained stable with
      an FEV1 of 30%. The presence of pre-transplant nontuberculous mycobacterial
      infection did not translate into recurrence of nontuberculous mycobacterial
      infection post-transplant. Whether it contributed to bronchiolitis obliterans
      syndrome remains unknown.

PMID- 30203905
TI  - C-H Bond Activation for the Synthesis of Heterocyclic Atropisomers Yields
      Hedgehog Pathway Inhibitors.
AB  - Axially chiral 4-arylisoquinolones are endowed with pronounced bioactivity, and
      methods for their efficient synthesis have gained widespread attention. However,
      enantioselective synthesis of axially chiral 4-arylisoquinolones by means of C-H
      activation has not been reported to date. Described here is a rhodium (III)
      catalyzed C-H bond activation and annulation for the atroposelective synthesis of
      axially chiral 4-arylisoquinolones. The method employs chiral cyclopentadienyl
      ligands embodying a piperidine ring as backbone and yields the atropisomers with
      good to excellent yields and enantioselectivity. Biological relevance of the 4
      arylisoquinolones was demonstrated by their investigation in different cellular
      assays, leading to the discovery of novel non-SMO (SMO= smoothened) binding
      Hedgehog pathway inhibitors.

PMID- 30203906
TI  - Boron(III)-Catalyzed C2-Selective C-H Borylation of Heteroarenes.
AB  - A BF3 ?Et2 O-catalyzed C2-selective C-H borylation of indoles with
      bis(pinacolato)diboron was developed to afford indole-2-boronic acid pinacol
      esters. A variety of functional groups were tolerated, and other heteroarenes
      like pyrrole and benzo[b]thiophene were also suitable substrates. An
      electrophilic substitution mechanism was proposed based on the preliminary
      mechanistic studies. This novel transformation utilizes simple and cheap BF3 ?Et2
      O as catalyst and exhibits unusual C2 regioselectivity, providing a significant
      non-transition-metal-catalyzed C-H borylation and an efficient method towards the
      synthesis of C2-functionalized heteroarenes.

PMID- 30203908
TI  - Improved recovery of human islets from young donor pancreases utilizing increased
      protease dose to collagenase for digesting peri-islet extracellular matrix.
AB  - Human islet isolation from young donor pancreases (YDP) utilizing the current
      purified standard dose of collagenase-protease enzyme mixtures often results in
      the release of a high percentage of mantled islets. Mantled islets are those
      surrounded by exocrine tissue and are difficult to purify by density gradient
      centrifugation, leading to poor islet recovery. Based on difference in
      extracellular matrix, and total collagen content between YDP and old donor
      pancreas (ODP, > 35 Y) led us to compare results from islet isolation using
      increased collagenase combination (ICC) or increased protease combination (IPC),
      to the standard enzyme combination (SEC) in a "trisected" pancreas model to
      overcome the donor-to-donor variability. These results showed a reduced
      percentage of mantled islets (17% +/- 7.5%) and higher postpurification islet
      recovery (83.8% +/- 5.6%) with IPC. Furthermore, these results were confirmed in
      13 consecutive whole pancreas islet isolations utilizing IPC from VitaCyte,
      Roche, or SERVA collagenase-protease enzyme mixtures. Results obtained from in
      vitro and in vivo islet functional assessment indicated that islets isolated
      using IPC retained normal islet morphology, insulin secretion, and the ability to
      reverse diabetes after transplantation in diabetic nude mice. This is the first
      report utilizing trisected pancreas to assess the effectiveness of different
      enzyme combinations to improve islet recovery from young donor pancreases.

PMID- 30203907
TI  - Rituximab in chronic inflammatory demyelinating polyradiculoneuropathy with
      associated diseases.
AB  - We aimed to analyse the response to rituximab in a cohort of chronic inflammatory
      demyelinating polyradiculoneuropathy (CIDP) patients with associated disorders.
      We conducted a clinical and electrophysiological retrospective monocentric study
      in 28 CIDP patients. Response to rituximab was defined as (a) a five-point
      increase in the Medical Research Council sum score or a one-point decrease in the
      Overall Neuropathy Limitations Scale score, compared to the score at the first
      rituximab infusion, or (b) the discontinuation of, or reduced need for, the last
      treatments before rituximab initiation. Twenty-one patients (75%) were responders
      to rituximab. The median time before response was 6 months (1-10 months). Only
      two patients needed to be treated again during a median follow-up of 2.0 years
      (0.75-9 years). Interestingly, the response rate was good in patients with
      associated autoimmune disease (5/8) and similar to the response rate observed in
      patients with a haematological disease (16/20) (P = 0.63). A shorter disease
      duration was associated with a better clinical response to rituximab (odds ratio
      0.81, P = 0.025) and the response rate was better (P = 0.05) in common forms
      (83.3%) than in sensory forms (42.9%). No major adverse events were recorded.
      Rituximab is efficacious in CIDP patients with haematological or autoimmune
      disease. It improves clinical response and decreases dependence on first-line
      treatments.

PMID- 30203909
TI  - Use of the Essential Nutrition Actions framework improved child growth in
      Bangladesh.
AB  - The Essential Nutrition Actions (ENA) framework is an evidence-based set of cost
      effective, integrated tools for training health and community workers to promote
      optimal nutrition practices for the first 1,000 days. This ENA pilot project
      (ENAPP) was implemented with United States Agency for International Development
      (USAID) funding from August 2008 to September 2009 in six unions of the working
      area of an existing USAID-funded, Title II programme in southern Bangladesh.
      ENAPP, which targeted governmental and non-governmental service providers, was
      intended to strengthen the behaviour change component of the nutrition strategy
      of this project. Following a qualitative review of ENAPP's activities, this
      evaluation uses administrative (growth monitoring) data and propensity score
      matching of pre-intervention characteristics to create multiple counterfactuals
      for difference-in-difference estimations of the impact of ENAPP on child
      nutritional status. Records indicated that government and community healthcare
      workers received intensive training, and these staff reported that they could
      effectively integrate ENA messages into their existing responsibilities. Both
      longitudinal and cross-sectional analyses indicate that ENAPP was successful in
      increasing children's weight-for-age z-scores, and the difference in z-scores
      between the treatment and the comparison group increased with time. The materials
      and methods used in this pilot project should be scaled up, based on the success
      of these tools and the project's ability to link with and influence the local
      health system.

PMID- 30203910
TI  - Sulfate-Based Cathode Materials for Li- and Na-Ion Batteries.
AB  - Electrochemical energy storage via Li-ion batteries has changed modern life
      drastically and has enabled technologies such as portable electronic devices,
      electric vehicles and stationary grid storage. However, with the steadfast
      technological evolution and increasing energy demands, batteries need to be
      constantly improved to meet the needs of our society. Furthermore, increasing
      concerns are raised regarding sustainability, availability of raw materials and
      cost. Therefore, extensive research efforts have been focused on the development
      of new battery types leading to the emergence of the Na-ion technology and the
      discovery of a myriad of new materials. In this context, polyanions became a
      prominent alternative to layered oxides. A large variety of polyanionic
      frameworks has been studied in the past years including phosphates, silicates and
      borates, but it was especially sulfates, which attracted a lot of attention due
      to their elevated operating voltages. The here presented article gives an
      overview of the exhaustive research on sulfate-based cathode materials for Li-
      and Na-ion batteries discussing recent findings and future perspectives.

PMID- 30203911
TI  - Premodified Surface Method to Obtain Ultra-highly Dispersed Metals and their 3D
      Structure Control on an Oxide Single-crystal Surface.
AB  - Precise control of the three-dimensional (3D) structure of highly dispersed metal
      species such as metal complexes and clusters attached to an oxide surface has
      been important for the development of next-generation high-performance
      heterogeneous catalysts. However, this is not easily achieved for the following
      reasons. (1) Metal species are easily aggregated on an oxide surface, which makes
      it difficult to control their size and orientation definitely. (2) Determination
      of the 3D structure of the metal species on an oxide powder surface is hardly
      possible. To overcome these difficulties, we have developed the premodified
      surface method, where prior to metal deposition, the oxide surface is premodified
      with a functional organic molecule that can strongly coordinate to a metal atom.
      This method has successfully provided a single metal dispersion on an oxide
      single-crystal surface with the 3D structure precisely determined by polarization
      dependent total reflection fluorescence X-ray absorption fine structure (PTRF
      XAFS). Here we describe our recent results on ultra-high dispersions of various
      metal atoms on TiO2 (110) surfaces premodified with mercapto compounds, and show
      the possibility of fine tuning and orientation control of the surface metal 3D
      structures.

PMID- 30203912
TI  - Organ distribution without geographic boundaries: A possible framework for organ
      allocation.
AB  - The Final Rule mandates that organ allocation not be based on the transplant
      candidate's place of residence or listing, except as required by sound medical
      judgment and best use of donated organs, to avoid wasting organs and futile
      transplants, and to promote access and efficiency. Current Organ Procurement and
      Transplantation Network (OPTN) policies use donation service areas and OPTN
      regions to distribute and allocate organs for transplant. These policies have
      recently been called into question as not meeting the requirements of the Final
      Rule. Therefore, we propose using borderless allocation scores that combine
      medical priority scores with geographic feasibility scores. Medical priority
      scores are currently used in OPTN allocation policy, for example, the model for
      end-stage liver disease and the lung allocation score. Geographic feasibility
      scores can be developed to account for the effects of ischemia due to travel
      times, donor characteristics that modify the feasibility of traveling due to
      organ outcomes, and the costs of shipping organs over long distances. A
      borderless distribution and allocation system could address the goals of equity
      and utility, while fulfilling the mandates of the Final Rule and providing
      optimal use of a scare resource.

PMID- 30203913
TI  - Preparation of Template-Free Robust Yolk-Shell Gelled Particles from Controllably
      Evolved All-in-Water Emulsions.
AB  - A template-free all-aqueous bulk preparation of robust hollow capsules having a
      gelatin shell from all-in-water double emulsions is reported. The hot (>40 
      degrees C) quaternary system water/polyethylene glycol (PEG)/gelatin/alginate is
      shown to spontaneously form PEG-in-gelatin-in-PEG double water emulsion droplets
      having a multinuclear core. These droplets are stable upon cooling below the
      temperature at which gelatin gelled. In contrast, above the melting temperature
      of gelatin, multinuclear double emulsion droplets controllably evolve into stable
      mononuclear yolk (aqueous PEG)-shell (gelatin) capsules dispersed in the aqueous
      PEG continuous phase. It is demonstrated that the gelatin shell can accommodate
      negatively charged latex beads and be re-enforced by glutaraldehyde or silica.
      These capsules are also shown to encapsulate payloads, suggesting possible
      applications in microencapsulation, drug delivery, and synthetic biology.

PMID- 30203914
TI  - Beneficial effects of tolvaptan on atrial remodeling induced by chronic
      intermittent hypoxia in rats.
AB  - INTRODUCTION: Atrial remodeling in the form of fibrosis is considered as the
      substrate for the development of atrial fibrillation (AF). The aim of this study
      was to investigate the effects of tolvaptan on chronic intermittent hypoxia (CIH)
      induced atrial remodeling and the mechanisms underlying such changes. METHODS: A
      total of 45 Sprague-Dawley rats were randomized into three groups: Control group,
      CIH group, CIH with tolvaptan treatment (CIH-T) group (n = 15). CIH rats were
      subjected to CIH 6 hour/d for 30 days, and CIH-T rats were administrated
      tolvaptan while they received CIH. After the echocardiography examination, rats
      were sacrificed in the 31 days. In each group, 5 rats were randomly selected for
      isolated heart electrophysiology testing, for other 10 rats, the tissues of atria
      were sampled for histological and molecular biological experiments, Masson's
      trichrome staining was used to evaluate the extent of atrial fibrosis, expression
      levels of microRNA-21 (miR-21), Sprouty-1 (Spry1), phosphatase, and tensin
      homolog (PTEN), extracellular regulated protein kinase (ERK), phospho
      extracellular regulated protein kinase (p-ERK), matrix metalloprotein 9 (MMP-9),
      phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), phospho-protein kinase
      B (p-AKT), nuclear factor-k-gene binding (NF-kappaB), phosphor-nuclear factor-k
      gene binding (p-NF-kappaB) were measured. RESULTS: Compared to the Control rats,
      CIH rats showed higher atrial interstitial collagen deposition and AF
      inducibility, mRNA levels of miR-21, MMP-9, PI3K, AKT, and protein levels of ERK,
      p-ERK, MMP-9, NF-kappaB, p-NF-kappaB were significantly increased, whereas mRNA
      levels of Spry1, ERK, and protein levels of Spry1, PTEN, PI3K, AKT, p-AKT were
      significantly decreased. Treatment with tolvaptan attenuated CIH-induced atrial
      fibrosis, reduced AF inducibility, expression levels of miR-21 and its downstream
      factors were also improved. CONCLUSIONS: CIH-induced significant atrial
      remodeling in our rat model, which was attenuated by tolvaptan. These changes may
      be explained due to alterations in miR-21/Spry1/ERK/MMP-9, miR-21/PTEN/PI3K/AKT,
      and NF-kappaB pathways by tolvaptan.

PMID- 30203915
TI  - Xantphos Doped POPs-PPh3 as Heterogeneous Ligand for Cobalt-Catalyzed Highly
      Regio- and Stereoselective Hydrosilylation of Alkynes.
AB  - A Co(acac)2 /POL-Xantphos@10PPh3 -catalyzed hydrosilylation of unsymmetrical
      internal alkynes with Ph2 SiH2 has been developed for the synthesis of highly
      selective syn-alpha-vinylsilane products. Furthermore, terminal alkynes were also
      used and gave the products with excellent regioselectivity and a wide functional
      group tolerance. Because this porous organic polymer combines the selectivity and
      activity merits of Xantphos with the stability advantage derived from the high
      concentration of PPh3 , the Co(acac)2 /POL-Xantphos@10PPh3 can be recycled
      multiple times without loss of activity and selectivity. This heterogeneous
      catalyst is expected to find promising applications in industrial synthesis.

PMID- 30203916
TI  - Applications of Dainshefsky's Dienes in the Asymmetric synthesis of Aza-Diels
      Alder Reaction.
AB  - Asymmetric hetero-Diels-Alder (AHDA) reactions provide a multitude of
      opportunities for the highly efficient, regio- and stereoselective construction
      of various heterocycles in enantiomerically pure form. The asymmetric aza-Diels
      Alder (A-aza-DA) reaction using diversely hetero-dienophiles and hetero-dienes
      have been increasingly developed as a valuable method for the synthesis of
      functionalized nitrogen ring systems. The purpose of this review is to give a
      detailed discussion of the A-aza-DA reaction particularly, the stereoselective
      reactions of imines as dienophiles with Dainshefsky dienes to obtain optically
      pure aza-Diels-Alder products. The development of stereoselective variants of the
      reaction make use of imines as the dienophile and Dainshefsky dienes is at the
      forefront of these studies. This review updates the A-aza-DA reactions covering
      the literature from 1972 till date.

PMID- 30203918
TI  - Biotic and Abiotic Synthesis of Renewable Aliphatic Polyesters from Short
      Building Blocks Obtained from Biotechnology.
AB  - Biobased polymers have seen their attractiveness increase in recent decades
      thanks to the significant development of biorefineries to allow access to a wide
      variety of biobased building blocks. Polyesters are one of the best examples of
      the development of biobased polymers because most of them now have their monomers
      produced from renewable resources and are biodegradable. Currently, these
      polyesters are mainly produced by using traditional chemical catalysts and harsh
      conditions, but recently greener pathways with nontoxic enzymes as biocatalysts
      and mild conditions have shown great potential. Bacterial polyesters, such as
      poly(hydroxyalkanoate)s (PHA), are the best example of the biotic production of
      high molar mass polymers. PHAs display a wide variety of macromolecular
      architectures, which allow a large range of applications. The present
      contribution aims to provide an overview of recent progress in studies on
      biobased polyesters, especially those made from short building blocks,
      synthesized through step-growth polymerization. In addition, some important
      technical aspects of their syntheses through biotic or abiotic pathways have been
      detailed.

PMID- 30203917
TI  - Bidirectional transfer of Anelloviridae lineages between graft and host during
      lung transplantation.
AB  - Solid organ transplantation disrupts virus-host relationships, potentially
      resulting in viral transfer from donor to recipient, reactivation of latent
      viruses, and new viral infections. Viral transfer, colonization, and reactivation
      are typically monitored using assays for specific viruses, leaving the behavior
      of full viral populations (the "virome") understudied. Here we sought to
      investigate the temporal behavior of viruses from donor lungs and transplant
      recipients comprehensively. We interrogated the bronchoalveolar lavage and blood
      viromes during the peritransplant period and 6-16 months posttransplant in 13
      donor-recipient pairs using shotgun metagenomic sequencing. Anelloviridae,
      ubiquitous human commensal viruses, were the most abundant human viruses
      identified. Herpesviruses, parvoviruses, polyomaviruses, and bacteriophages were
      also detected. Anelloviridae populations were complex, with some donor organs and
      hosts harboring multiple contemporaneous lineages. We identified transfer of
      Anelloviridae lineages from donor organ to recipient serum in 4 of 7 cases that
      could be queried, and immigration of lineages from recipient serum into the
      allograft in 6 of 10 such cases. Thus, metagenomic analyses revealed that viral
      populations move between graft and host in both directions, showing that organ
      transplantation involves implantation of both the allograft and commensal viral
      communities.

PMID- 30203919
TI  - Tuning the Electron Affinity and Stacking Properties of Corannulene by
      Introduction of Fluorinated Thioethers.
AB  - Trifluoromethylthio-substituted corannulene can be easily synthesized in good
      yield by the reaction of iodocorannulene with CuSCF3 . Oxidation with meta
      chloroperbenzoic acid (mCPBA) yields the corresponding sulfonyl compound which
      exhibits the largest anodic shift of the redox potential caused by a single
      substituent. Similarly, four SCF3 , SC6 F5 and SeC6 F5 substituents are
      introduced in the 1,2,5,6-positions of corannulene starting with 1,2,5,6
      tetraiodo- or 1,2,5,6-tetrabromocorannulene, respectively. The reactions are
      performed in polar aprotic solvents and are believed to follow SN Ar-type
      substitution mechanisms. Crystal and molecular structures of selected compounds
      were elucidated by X-ray crystallography. Trifluoromethanesulfonyl corannulene
      and the fourfold-substituted trifluoromethylthioether exhibit a perfect columnar
      stacking of the bowls. The substituted corannulenes were investigated
      electrochemically by cyclic voltammetry giving raise to large anodic shifts owing
      to substitution with electron-withdrawing groups.

PMID- 30203920
TI  - Calcified cerebral emboli: Incidence and implications - How do you know an
      embolism is calcific?

PMID- 30203921
TI  - Governing through lifestyle-Lalonde and the biopolitical management of public
      health in Canada.
AB  - In 1974, the Liberal government of Pierre Trudeau released a "green paper" known
      as the Lalonde Report, after the health minister at that time. The report
      formulated perspectives on health and the main concepts and ideas developed in
      it, particularly the concept of "lifestyle," which became the foundation of
      public health policies in many different European countries and the United
      States. The concept of "lifestyle" connected personal behaviour and habits to the
      individual health condition; people were not dying due to a lack of access to
      medical care but because they lived a life prone to personal risk taking.
      Furthermore, what is seldom discussed is that this report not only propagated the
      (neo)liberal view of citizens as autonomous rational actors (homo oeconomicus),
      with personal responsibility for their health, but it was a first step in the
      transformation of Medicare and went far beyond the question of health promotion.
      Health was no longer something that happened to a person but was created through
      personal choice and, therefore, one had to assume responsibility for one's
      behaviour. Using Foucault's definition of government as the "conduct of conduct,"
      we will demonstrate that the Lalonde report must be understood as a specific
      "technology of government" and contributed to a neoliberal transformation of
      health care despite the fact that the Canadian system of Medicare was based on
      the idea of universality, meaning citizens had equal access to health care
      independent of their socio-economic situation. As we will demonstrate, the
      Lalonde report undermined this foundation and initiated a profound reorientation,
      not only of the healthcare system, but even more importantly, it radically
      changed the way we think about our behaviour around health-related issues. We
      will also discuss how the making of the report contributed to the redefinition of
      politics and demonstrated a lack of concern with liberal-democratic decision
      making processes.

PMID- 30203922
TI  - Gold(I)-Coumarin-Caffeine-Based Complexes as New Potential Anti-Inflammatory and
      Anticancer Trackable Agents.
AB  - Three new gold(I)-coumarin-based trackable therapeutic complexes and two non
      trackable analogues have been synthesised and fully characterised. They all
      display anti-proliferative properties on several types of cancer cell lines,
      including those of colon, breast, and prostate. Two complexes displayed
      significant anti-inflammatory effects; one displayed pro-inflammatory behaviour;
      this highlights the impact of the position of the fluorophore on the caffeine
      scaffold. Additionally, the three coumarin derivatives could be visualised in
      vitro by two-photon microscopy.

PMID- 30203923
TI  - Polar Effects Control the Gas-Phase Reactivity of para-Benzyne Analogs.
AB  - We report herein a gas-phase reactivity study on a para-benzyne cation and its
      three cyano-substituted, isomeric derivatives performed using a dual-linear
      quadrupole ion trap mass spectrometer. All four biradicals were found to undergo
      primary and secondary radical reactions analogous to those observed for the
      related monoradicals, indicating the presence of two reactive radical sites. The
      reactivity of all biradicals is substantially lower than that of the related
      monoradicals, as expected based on the singlet ground states of the biradicals.
      The cyano-substituted biradicals show substantially greater reactivity than the
      analogous unsubstituted biradical. The greater reactivity is rationalized by the
      substantially greater (calculated) electron affinity of the radical sites of the
      cyano-substituted biradicals, which results in stabilization of their transition
      states through polar effects. This finding is in contrast to the long-standing
      thinking that the magnitude of the singlet-triplet splitting controls the
      reactivity of para-benzynes.

PMID- 30203924
TI  - The dishonest gambler: Low HEXACO honesty-humility and gambling severity in a
      community sample of gamblers.
AB  - Personality dimensions have been found to be important in understanding the
      aetiology of disordered gambling. While the majority of research has focused on
      the Five-Factor Model of personality, recent empirical evidence also indicated
      that the honesty-humility factor of the HEXACO personality model may be a key
      personality correlate of gambling behaviour. In the present research, we extend
      the understanding between personality and gambling severity by further assessing
      whether HEXACO dimensions are associated with both current gambling status and
      gambling severity in a community-recruited sample of gamblers (N = 427). In
      addition, we examined whether motivations to engage in gambling (enhancement,
      coping, social and financial) mediated the relationship between personality and
      gambling severity on the Problem Gambling Severity Index. Demographic covariates
      were controlled for in our analyses. The results indicate that honesty-humility
      was the only personality dimension that significantly predicted gambling status
      (non-gamblers vs. current gamblers). In addition, lower scores on honesty
      humility, conscientiousness and openness were significantly associated with
      gambling severity. Lastly, coping motives were the only significant mediator in
      the relationship between honesty-humility and increased gambling severity. The
      results offer further support to the notion that honesty-humility may be an
      especially pertinent personality dimension in understanding the aetiology of
      disordered gambling. (c) 2018 John Wiley & Sons, Ltd.

PMID- 30203925
TI  - Improved diagnostic precision of urine cytology by implementation of The Paris
      System and the use of cell blocks.
AB  - BACKGROUND: The Paris System for Reporting Urinary Cytology (TPS) published in
      2016 provides a standardized approach to evaluating urine cytology. In the
      authors' practice, a TPS-like approach was adopted in 2012 using similarly
      defined cytologic criteria and correlating cystoscopic findings, and they also
      began incorporating the use of cell block (CB) material. The objective of the
      current study was to assess whether this TPS-like approach with the use of CB, as
      well as direct implementation of TPS, improved the diagnostic value of urine
      cytology. METHODS: In total, 188 consecutive urine cytology specimens from 2010
      through 2016 that had concurrent or subsequent histologic specimens available
      were retrospectively analyzed for diagnostic correlation. Urine cytology
      performance was compared between the periods 2010 to 2012 (pre-TPS-like), 2013 to
      2016 (TPS-like), and after TPS reclassification, including blind review by a
      cytopathologist. The contribution of available CB material to final diagnoses
      also was assessed. RESULTS: Both the TPS-like approach and TPS reclassification
      resulted in significantly lowering the rate of atypical urothelial cells (AUC)
      diagnosis from 48%, to 21%, to 9% (from pre-TPS, to TPS-like, to after TPS
      reclassification, respectively; P < 0.01) while increasing the positive
      predictive value of an AUC diagnosis for high-grade urothelial carcinoma from
      21%, to 43%, to 83%, respectively. The use of CBs contributed to a definitive
      final diagnosis in 24 of 36 cases (66.7%). CONCLUSIONS: In support of the new TPS
      recommendations, the application of stringent "TPS-like" and TPS criteria
      improves the value of an AUC diagnosis for clinicians and patients by lowering
      the AUC rate and increasing the positive predictive value of AUC for high-grade
      urothelial carcinoma. CBs can be used to help resolve problematic cases for more
      definitive diagnostic categorization.

PMID- 30203926
TI  - The effects of adenoidectomy on the smell perception of children.
AB  - BACKGROUND: In this study, we employed a novel children's olfactory test in order
      to more accurately assess the relationship between nasopharyngeal obstruction and
      odor identification ability. We quantified the impact of adenoidectomy on
      olfactory function, established whether the influences of the operation were
      related to the preoperative amount of nasopharyngeal obstruction, and determined
      whether sex influenced the olfactory measures. METHODS: Fifty-three boys and 23
      girls were administered a standardized children's olfactory test, the Pediatric
      Smell WheelTM, before and 45 days after adenoidectomy. They ranged in age from 5
      to 12 years and exhibited varying degrees of adenotonsillar hypertrophy and
      histories of recurrent adenotonsillitis. Radiographs of the nasopharynx were used
      to grade the degree of nasopharyngeal obstruction. RESULTS: Significant
      postoperative improvement in smell function occurred more frequently in children
      with >50% preoperative obstruction of the nasopharynx. In this group, average
      function improved 50.8% after surgery (95% confidence interval [CI], 39.1% to
      64%). Improvement on 9 of the 11 odors was present, with significant differences
      occurring for the odors of bubble gum, baby powder, mint, and cinnamon. No sex
      differences were evident. CONCLUSION: Olfactory dysfunction occurs primarily in
      children whose nasopharyngeal obstruction is >50%. Removal of the hypertrophied
      adenoids returned smell function back to normal in these cases. This study
      suggests that smell loss may be of value in decisions regarding whether or not to
      perform adenoidectomy in children with nasopharyngeal obstruction.

PMID- 30203927
TI  - Computational aeroacoustics to identify sound sources in the generation of
      sibilant /s/.
AB  - A sibilant fricative /s/ is generated when the turbulent jet in the narrow
      channel between the tongue blade and the hard palate is deflected downwards
      through the space between the upper and lower incisors and then impinges the
      space between the lower incisors and the lower lip. The flow eddies in that
      region become a source of direct aerodynamic sound, which is also diffracted by
      the speech articulators and radiated outwards. The numerical simulation of these
      phenomena is complex. The spectrum of an /s/ typically peaks between 4 and 10
      kHz, which implies that very fine computational meshes are needed to capture the
      eddies producing such high frequencies. In this work, a large-scale computation
      of the aeroacoustics of /s/ has been performed for a realistic vocal tract
      geometry, resorting to two different acoustic analogies. A stabilized finite
      element method that acts as a large eddy simulation model has been adopted to
      solve the flow dynamics. Also, a numerical strategy has been implemented that
      allows the determination, in a single computational run, of the separate
      contribution of the sound diffracted by the upper incisors from the overall
      radiated sound. Results are presented for points located close to the lip opening
      showing the relative influence of the upper teeth depending on frequency.

PMID- 30203928
TI  - Nocturnal enuresis and sleep disordered breathing in primary school children:
      Potential implications.
AB  - INTRODUCTION: The association between nocturnal enuresis (NE) and sleep
      disordered breathing (SDB) has been repeatedly reported, but has primarily been
      focused on clinical cohorts. The purpose of this study, was to assess whether SDB
      related symptoms such as snoring and unrefreshing sleep in the morning are
      associated with NE in a large-scale community school-based survey. METHODS: A
      cross-sectional assessment using a standard questionnaire was conducted on nearly
      20 000 primary school children (5-12 years old) in Matsuyama, Japan. Associations
      between NE and the frequencies of snoring and unrefreshing sleep were evaluated
      using multivariate logistic and regression analyses. RESULTS: Multivariate
      adjusted odds ratios (95% confidence intervals) for enuresis were 1.21 (1.04 to
      1.40) and 1.36 (1.07 to 1.73) in boys who snored 1 or 2 nights per week and >=3
      nights per week, respectively (P for trend <0.0001). Those for enuresis were 1.67
      (1.41 to 1.99) and 1.96 (1.63 to 2.36) in boys who showed unrefreshing sleep 1 or
      2 nights per week and >=3 nights per week, respectively (P for trend <0.0001).
      Significant associations between NE and snoring frequency emerged among children
      who did not report unrefreshing sleep (P-trend for boys and girls were <0.0001
      and <0.01, respectively), while significant associations between NE and frequency
      of unrefreshing sleep were detected among children who snored >=1 nights per week
      (P for trend >0.1). CONCLUSIONS: The pathogenic mechanisms linking snoring and
      unrefreshing sleep to increased risk of NE are unknown. However, snoring, a
      surrogate reporter of SDB, is associated with increased urine production, while
      unrefreshing sleep may result from disrupted sleep facilitating increased sleep
      pressure and elevated arousal thresholds. Thus, both SDB and unrefreshing sleep
      are potential independent risk factors of NE in school age children.

PMID- 30203929
TI  - Is it useful to repeat MRI of the sacroiliac joints after three months or one
      year in the diagnostic process of patients with chronic back pain suspected of
      axial spondyloarthritis?
AB  - OBJECTIVE: To investigate the value of repeating MRI of the sacroiliac joints
      (MRI-SI) in the diagnostic process of early chronic back pain patients (CBP)
      suspected of axial SpondyloArthritis (axSpA) and study determinants of MRI-SI
      positivity. METHODS: Patients with CBP (duration: >=3 months, <=2 year, onset <45
      years) with >=1 SpA-feature included in the SPondyloArthritis Caught Early cohort
      underwent baseline, three months and one year visits with evaluation of all SpA
      features and repeated MRI-SI. MRI-SI-positivity according to ASAS was assessed by
      two (or three) well-trained readers, blinded for clinical information. Factors
      determining MRI-SI-positivity over follow-up were calculated by GEE analysis.
      RESULTS: Of the 188 patients (38.3% male, mean (SD) age 31.0 (8.2) years, symptom
      duration 13.2 (7.1) months), 31 (16.5%) were MRI-SI-positive at baseline. After
      three months and one year 3/27 (11.1%) and 11/29 (37.9%) patients changed from
      MRI-SI positive to negative, respectively which was partly induced by the start
      of anti-TNF therapy. Changes from negative to positive were seen in 5/116 (4.3%)
      and 10/138 (7.2%) patients, respectively. HLA-B27-positivity and male gender
      independently determined the likelihood of a positive MRI at any time point (42%
      in HLA-B27+ men and 6% in HLA-B27- females). If the baseline MRI is negative, the
      likelihood of a positive MRI during follow-up is very low (max 7%). CONCLUSION:
      MRI-SI ASAS status changes are seen in a minority of the patients. Both male
      gender and HLA-B27-positivity are important predictors of MRI-positivity.
      Repeating MRI after three months or one year in the diagnostic work-up in early
      disease is not useful. This article is protected by copyright. All rights
      reserved.

PMID- 30203930
TI  - Updated protocols for the detection of Sotatercept and Luspatercept in human
      serum.
AB  - We recently published two protocols for the detection of Sotatercept (ACE-011,
      ACVR2A-Fc) and Luspatercept (ACE-536, ACVR2B-Fc) in human serum. Both methods
      used covalently immobilized antibodies on agarose beads for immunoprecipitation
      and SAR-PAGE/Western blotting for detection. Disadvantages were the relatively
      high amount of antibody required per sample (10 MUg) and the need of a secondary
      antibody for the final detection. The updated protocols overcome these
      limitations by antigen-antibody complex formation in solution followed by capture
      of the complex with anti-antibody-coated magnetic beads. They also omit the
      secondary antibody incubation step by usage of biotinylated primary antibodies,
      which can be directly incubated with streptavidin-HRP. Thus, the new protocols
      are faster, simpler, and cheaper and offer comparable sensitivities.

PMID- 30203931
TI  - Using 'draw, write and tell' to understand children's health-related experiences.
AB  - BACKGROUND: In recognising the capability and rights of children to express their
      experiences, 'draw, write and tell' (DWT) has emerged as a participatory
      qualitative research method. DWT enables children to communicate their
      experiences by drawing, writing words and telling the story of their pictures in
      response to interview questions. AIM: To discuss the challenges and benefits of
      using DWT to explore children's experiences of pain. DISCUSSION: Aspects that
      affect the quality of data in DWT include the materials used and the influences
      of the primary caregiver. Experience suggests that if trust between the child and
      researcher has been established, the duration of the interview is unimportant.
      CONCLUSION: While many methods of analysis can be used with data gathered using
      DWT, it is important to ensure children's perspectives are represented
      accurately. Furthermore, children's capacity as active participants in research
      should be reflected. IMPLICATIONS FOR PRACTICE: Future studies could examine the
      potential of using drawings to share information in adult and paediatric clinical
      settings.

PMID- 30203932
TI  - On the Relationship between Cognitive Ability and Risk Preference.
AB  - Many decisions of individuals involve a combination of internal preferences and
      mental processes related to cognitive ability. As Frederick (2005) argued in this
      journal, "there is no good reason for ignoring the possibility that general
      intelligence or various more specific cognitive abilities are important causal
      determinants of decision making." Since then, a number of empirical studies have
      focused on the relationship between cognitive ability and decision-making in
      different contexts. This paper will focus on the relationship between cognitive
      ability and decision-making under risk and uncertainty. Taken as a whole, this
      research indicates that cognitive ability is associated with risk-taking behavior
      in various contexts and life domains, including incentivized choices between
      lotteries in controlled environments, behavior in nonexperimental settings, and
      self-reported tendency to take risks. We begin by clarifying some important
      distinctions between concepts and measurement of risk preference and cognitive
      ability. In particular, complexity and possible confusions arise because observed
      measures of risk preference and cognitive ability are used to represent the
      latent characteristics of these concepts. We discuss the substantial (and
      somewhat implausible) range of assumptions that need to be satisfied in order to
      be able to interpret a correlation between measures of risk preference and
      cognitive ability as a relationship between latent risk preference and latent
      cognitive ability. Drawing causal inferences from such relationships raises
      additional challenges. We go on to argue that it is nevertheless important and
      valuable to study whether cognitive ability is related to measured risk
      preference (see also Dohmen, Falk, Huffman, and Sunde 2010). Risk preference is
      typically measured by risky behavior (actual or self-reported). If risky behavior
      varies systematically with cognitive ability, this may reinforce or counteract
      the impact of cognitive ability on life outcomes, depending on the nature of the
      correlation. If there is a relationship, it also becomes important to control for
      cognitive ability when relating life outcomes to standard revealed preference
      measures of risk preference. If cognitive ability has a causal impact on measured
      risk preference, it is important to understand the mechanism, and some intriguing
      policy implications arise. We then take stock of what is known empirically on the
      connections between cognitive ability and measured risk preferences, looking at
      studies using real-world risky behavior, experimental measures of risky choice,
      and self-reported measures of willingness to take risks. One pattern that emerges
      frequently in these studies is that cognitive ability tends to be positively
      correlated with avoidance of harmful risky situations, but it tends to be
      negatively correlated with risk aversion in advantageous situations. This
      suggests that the relationship between cognitive ability and risk taking has a
      reinforcing effect on economic outcomes. There is also intriguing emerging
      evidence that measured risk preference is particularly strongly related to
      certain facets of cognitive ability, those that facilitate quantitative problem
      solving, with implications for understanding mechanisms and possibly for better
      targeting policy interventions. We conclude by discussing perspectives for future
      research, in particular the scope for the development of richer sets of
      elicitation instruments and measurement across a wider range of concepts. We also
      consider progress in neuroscience, but conclude that at present that field still
      seems relatively far from allowing definitive conclusions about latent risk
      preference and cognitive ability. Nevertheless, the existing empirical evidence
      suggests that interventions to influence cognitive ability, should they be
      possible, might have spillovers on risky choice.

PMID- 30203933
TI  - Are Risk Preferences Stable?

PMID- 30203934
TI  - Risk Preference: A View from Psychology.

PMID- 30203935
TI  - Comparison of diagnostic efficacy by two urine PCA3 scores in prostate cancer
      patients undergoing repeat biopsies: a meta-analysis.
AB  - BACKGROUND: Urine prostate cancer gene 3 (PCA3) is significantly elevated in
      patients with prostate cancer and can be used for the diagnosis of prostate
      cancer, but its cutoff value is still controversial. METHODS: We searched the
      database on urine PCA3 in the diagnosis of prostate cancer, such as Medline, Web
      of Science, the Cochrane Library and Embase. Meta-analysis was performed using
      the random effect model and the sensitivity, specificity, diagnostic odds ratio,
      and area under the ROC curve (SROC) were calculated. RESULTS: Our meta-analysis
      included nine studies on PCA3 scores in a total of 1721 suspected prostate cancer
      patients. When urine PCA3 score was 20, we obtained sensitivity of 0.83,
      specificity of 0.40, diagnostic odds ratio of 3.11, and the area under the SROC
      curve was 0.6842 (Q value =0.6404). When urine PCA3 score was 35, we found a
      lower sensitivity of 0.66, a higher specificity of 0.63 and a relatively lower
      diagnostic odds ratio of 2.84. The area under the SROC curve was 0.6715, which
      was slightly lower than urine PCA3 score 20. CONCLUSIONS: Our meta-analysis
      suggested that when the PCA3 score cutoff value was 20, the unnecessary puncture
      was reduced and obtained a higher diagnostic efficacy.

PMID- 30203936
TI  - The pathologist's role in the detection of rare variants of bladder cancer and
      analysis of the impact on incidence and type detection.
AB  - BACKGROUND: Histology is one of the most important factors determining the
      prognosis of bladder cancers and rare variants are generally associated with
      decreased disease specific survival compared to pure transitional cell
      carcinomas. We believe that rare bladder cancer variants are likely
      underdiagnosed in the absence of a dedicated uro-pathologist in many centers. The
      objective of this study is to evaluate the contribution of a dedicated uro
      pathologist on the identification of rare bladder cancer variants. METHODS: We
      retrospectively analyzed the clinical and histological records of all patients
      which underwent a radical cystectomy and lymph node dissection between January
      2000 and September 2015. The sample was divided in two groups: Group A, consists
      of patients who underwent radical cystectomy n the absence of a dedicated uro
      pathologist at our institution, whereas the Group B consists of patients who
      underwent surgery when a dedicated uro-pathology service was available. We then
      evaluated the impat of a dedicated uro-pathologist on rare variants detection.
      RESULTS: 137/551 (24.9%) of patients who underwent RC had at least one rare
      variant. In Group A 38/238 (16%) of patients showed a rare variant, while 99/313
      (31.6%; p value: < 0,001) in Group B. Furthermore, the diagnosis of sarcomatoid
      variant was statistically significantly less common in Group A (p = 0.0026). The
      concordance between final radical cystectomy histology and previous TURBT
      histology was poor in both groups (overall 50.4%). CONCLUSIONS: The presence of a
      dedicated urological anatomical pathologist is of paramount importance and
      significantly increases the detection rate of not-transitiona cell carcinoma
      bladder cancer types, but it does not increase the concordance rate between
      histological diagnoses in TURBT and radical cystectomy specimens.

PMID- 30203937
TI  - Risk factors for the delay in the diagnosis of penile lesions: results from a
      single center in Italy.
AB  - BACKGROUND: Early diagnosis is fundamental for the investigation and treatment of
      penile lesions. There is an unfortunate documented delayed in presentation and
      diagnosis of penile lesions. Literature is scant regarding the risk factors
      contributing to this delay in a Mediterranean population. Few previous reports
      are published in entirely different homogeneous populations. The objective of
      this study is to provide an analysis of the causes and risk factors related to
      the delay of the first medical visit in a North Italian population subgroup.
      METHODS: From September 2004 to September 2017, 184 consecutive patients were
      treated at our institute with a surgical approach for a penile lesion. The
      epidemiological factors and reasons for the delay to diagnosis were recorded
      during personal or telephonic interviews. Univariate logistic regression models
      were performed to screen for an effect of the clinical and demographic variables
      on the delay in diagnosis. Variables with a p-value of less than 0.05 were
      entered into multivariate analysis, where the delay in diagnosis was the
      dependent variable. RESULTS: One hundred and thirteen patients were enrolled. The
      average patient age was fifty-eight. The average delay between the appearance of
      the lesion and the first medical consultation was fifty- three days. The
      principal cause of delay was the lack of knowledge of penile lesions and
      secondly, the feeling of embarrassment of having to visit a doctor. The
      multivariate analysis reported a significant correlation between the level of
      education, sexual activity and extramarital affairs on the delay in presentation
      (p-values respectively: 0.01, 0.009 and 0.04). CONCLUSIONS: Patients education
      regarding this pathology and its potential danger is inadequate and thus it is
      necessary to implement a campaign of information and prevention in order to
      reduce delayed diagnosis.

PMID- 30203938
TI  - Clinical and histopathological features of carcinosarcoma of the renal pelvis: a
      systematic review of a rare tumour.
AB  - INTRODUCTION: Carcinosarcoma of the kidney pelvis (CRP) is a rare but not
      exceptionally unique tumor in which in literature are reported almost only case
      studies and small series. We aim to provide a comphrensive overview of the
      disease, examining epidemiology, symptoms, pathological features, treatment and
      outcomes which are still missing, in order to offer a landmark paper to
      urologists which have to manage patients with this type of disease. EVIDENCE
      ACQUISITION: A review of the current literature was conducted through the NCBI
      PubMed database in June 2017 following the updated PRISMA guidelines. The filters
      used for the research were the following: "carcinosarcoma renal pelvis",
      "carcinosarcoma kidney pelvis" and "urinary tract carcinosarcoma.". Only studies
      with confirmed histological diagnosis of CRP and a description of patient
      characteristics (demographics and/or pathological) were included in the review.
      EVIDENCE SYNTESIS: Only 15 studies fulfilled the inclusion criteria. The main
      symptom at presentation was macroscopic haematuria, followed by abdominal pain.
      The carcinomatous pattern made of Transitional Cell carcinoma in 73.3% of
      patients and squamous carcinoma in 33%, while the sarcomatoid was spindle cells
      in 40% of patients, chondrosarcoma and undifferentiated in 33.3%. Despite radical
      surgical treatment was performed in all patients, there are no articles reporting
      a survival rate of more than 2 years. CONCLUSIONS: Carcinosarcoma of the kidney
      is a rare tumor of which little is known, especially about pathogenesis and
      oncological outcomes in the different therapeutic approaches described. Current
      literature is almost exclusively a case report that does not provide adequate
      information especially about survival and progression free survival. The creation
      of a shared database could in a matter of years lead us to increase the
      information about the oncological outcomes of the various possible treatments.

PMID- 30203939
TI  - The occurrence of intraoperative complications during partial nephrectomy has a
      significant impact on postoperative outcome: results from the RECORd1 project.
AB  - BACKGROUND: We sought to analyze the predictive factors of intraoperative
      complications in patients submitted to PN and the impact of intraoperative
      complications on postoperative outcomes. METHODS: Data of 1055 patients who
      underwent PN for cortical renal masses were recorded from a multicenter
      prospective observational study (RECORd1 project). RESULTS: Overall, 48 (5%)
      patients experienced 49 intraoperative complications (4 medical, 45 surgical). At
      multivariable analysis, age (OR 1.02, CI 1.00-1.08 p=0.03), imperative vs
      elective surgical indication (OR 2.55, CI 1.12-5.85, p=0.03), open (OR 5.76,
      95%CI 1.05-9.21, p=0.01) and laparoscopic (OR 2.35, CI 1.11-4.95, P=0.03) vs
      robotic approaches resulted independent predictive factors of intraoperative
      complications. Patients experiencing intraoperative complications had a
      significantly higher rate of overall postoperative complications (41.6% vs 17.3%,
      p<0.0001), surgical postoperative complications (29.2% vs. 12.6%, p<0.0001),
      Clavien 2 surgical postoperative complications (14.6% vs 7.2%, p=0.05) and a
      significantly longer length of stay (8 (6-9) vs 7 (5-8) days, p<0.0001) than
      those with an uneventful intraoperative course. CONCLUSIONS: Efforts should be
      made to minimize the risk of intraoperative complications during PN, and, in that
      case, patients should be carefully monitored.

PMID- 30203940
TI  - "No Ordinary Lawsuit": Climate Change, Due Process, and the Public Trust
      Doctrine.
AB  - On November 10, 2016, just two days after the election of President Donald Trump,
      the federal district court in Oregon handed down Juliana v. United States. This
      remarkable decision refused to dismiss a lawsuit brought by youth plaintiffs who
      claimed that the federal government's fossil fuel policies over the years, which
      have produced an atmosphere with dangerous levels of greenhouse gases (GHGs),
      violated the federal public trust doctrine (PTD) and their federal constitutional
      rights to due process and equal protection. The court found a constitutional
      right to a stable climate system, determining that the PTD was an implicit part
      of due process and enforceable through the Constitution's due process clause. At
      trial, if the youth plaintiffs are able to prove that for decades the government
      willfully disregarded information about the potential catastrophic effects of GHG
      pollution, or abdicated its public trust duties, the decision could be
      transformative in global efforts to shift to an energy policy that does not
      threaten young people and future generations. This Article examines Juliana, its
      context as part of a worldwide campaign of "atmospheric trust" litigation, its
      path-breaking reasoning, and its implications in the United States and abroad.
      The case has been described as "the case of the century" and, because of the harm
      it aims to address and the fundamental rights approach endorsed by the court, it
      just may be that. Pending the forthcoming trial and almost certain appeals, we
      think the case is, as the trial judge accurately recognized, "no ordinary
      lawsuit."

PMID- 30203941
TI  - [Typical Medicinal Plants Community and Diversity Research in Altay Region of
      Xinjiang].
AB  - Objective: To investigate typical medicinal plants of Rheum altaicum, Glycyrrhiza
      uralensis, Ferula sinkiangensis, Paeonia sinjiangensis, Ephedra equisetina, and
      Origanum vulgare in Altay region of Xinjiang, and to clarify their current
      existing situation under natural condition. Methods: Based on the 30 sample
      plots, ecological methods were used for investigating the community structure and
      species diversity of local medicinal plants. Results: 39 species belonging to 20
      families,36 genera were recorded in the area. Xerophytic shrubs, half shrubs and
      herbs were dominant plants. The important values of six typical medicinal plants
      were 0. 32,0. 37,0. 42,0. 50,0. 49 and 0. 34,respectively. Six indexes of species
      diversity were generally low( 0. 63 ~ 0. 80),in which the species diversity
      indexes of Paeonia sinjiangensis, Ferula sinkiangensis, and Rheum altaicum were
      the highest( 0. 80,0. 80 and 0. 76),the species diversity indexes of Ephedra
      equisetina and Origanum vulgare were lower( 0. 74 and 0. 64),and the species
      diversity index of Glycyrrhiza uralensis was the lowest( 0. 63). Conclusion:
      Composition and community structure of medicinal plant species in Altay region of
      Xinjiang were relatively simple, which need to be protected urgently.

PMID- 30203942
TI  - [Molecular Identification on Three Medicinal Phlomis Species Produced in Yunnan
      Province Based on ITS and matK].
AB  - Objective: To analyze ITS region and matK gene sequences of three medicinal
      Phlomis plants,in order to provide molecular basis for identifying and protecting
      their wild resources. Methods: PCR and sequencing were conducted on Phlomis
      likiangensis,Phlomis melanantha and Phlomis betonicoides wild populations by
      primers pairs ITS4 / ITS5 and matKXF / matK5 R. Results: The smallest inter-K2 P
      genetic distance was further than the largest intra-K2 P genetic distance in
      Phlomis likiangensis, Phlomis melanantha and Phlomis betonicoides. Different
      samples of three medicinal Phlomis plants were gathered together and could be
      distinguished from other exogenous species by Neighbor-Joining( NJ) tree. Phlomis
      likiangensis, Phlomis melanantha and Phlomis betonicoides had three, three and
      one sites on ITS2 for their effective identification, and had three,three and
      three sites on ITS1 for their effective identification respectively. Phlomis
      betonicoides had three sites on matK for its effective identification, while
      Phlomis likiangensis or Phlomis melanantha needed multiple sites for their
      effective identification. Conclusion: The study implies that ITS1,ITS2 and matK
      fragments could be used for molecular identification of Phlomis likiangensis,
      Phlomis melanantha and Phlomis betonicoides.

PMID- 30203943
TI  - [DNA Barcoding of Mongolian Medicinal Plant Scutellaria scordifolia].
AB  - Objective: To authenticate Scutellaria scordifolia and its closely related
      species using ITS2 sequence. Methods: Total genomic DNA was isolated from
      Scutellaria scordifolia and its related species. Nuclear DNA ITS2 sequences were
      amplified and sequenced,and ITS2 sequences of the other species of plants were
      obtained in Gen Bank,The Kimura 2-parameter( K2P) distances were calculated.
      Identification analyses were performed using Neighbor-joining( NJ) and secondary
      structure of ITS2 sequence methods. Results: The genetic distances of ITS2
      between Scutellaria scordifolia and its closely related species were 0. 014 ~ 0.
      141,which were obviously higher than those in the intra-species of Scutellaria
      scordifolia. The NJ tree and secondary structure of ITS2 sequence can distinguish
      Scutellaria scordifolia and its closely related species. Conclusion: ITS2
      sequence can effectively and accurately identify the Mongolian medicinal plant
      Scutellaria scordifolia and its closely relatives.

PMID- 30203944
TI  - The Fallacy of Choice: the Destructive Effect of School Vouchers on Children With
      Disabilities.
AB  - This Article addresses the impact of school voucher programs on students with
      disabilities. We show that for children with disabilities, the price of admission
      into so-called "school choice" programs is so high that it is effectively no
      realchoice at all. School voucher programs require students with disabilities to
      sign away their robust federal rights and protections in the public school
      system. Under the Individuals with Disabilities Education Act (IDEA)--the
      preeminentlegislative safeguard for students with disabilities--these rights
      include the right to a "free and appropriate public education" delivered through
      an "individualized education plan." By giving up these protections, children with
      disabilities are left at the mercy of private schools that have no legal
      obligation to provide them with an appropriate education, and, in the vast
      majority of cases, are not legally prohibited from discriminating against them on
      the basis of their disability. We argue that school voucher programs--including a
      proposed federal voucher program--put the education of students with disabilities
      back decades, and likely constitute a violation of the Equal Protection Clause of
      the U.S. Constitution.

PMID- 30203945
TI  - [SCoT Analysis on Genetic Diversity of Medicinal Fungus Cordyceps militaris].
AB  - Objective: To analyze the genetic diversity of medicinal fungus of 27 strains of
      Cordyceps militaris. Methods: Unweighted pair-group method with arithmetic means(
      UPGMA) and principal coordinate analysis( PCoA) were used to determine the
      genetic diversity of 27 Cordyceps militaris strains based on start codon targeted
      polymorphism( SCoT). Results: Based on eight informative primers,a total of 59
      bands were produced,and 94. 33% of them were polymorphic. The average of
      polymorphism bands was 6. 875. The results suggested that great genetic diversity
      existed in Cordyceps militaris. Basically,27 strains were separated into six
      groups using UPGMA method,while three groups when using PCoA method,which showed
      that genetic diversity of Cordyceps militaris samples were related to their
      geographical origins. Conclusion: SCoT markers are informative and could be used
      to detect polymorphism for medicinal fungus of Cordyceps militaris strains.

PMID- 30203946
TI  - [Optimization of Suitable Drying Processing Methods of Angelica dahurica].
AB  - Objective: To optimize the suitable drying processing methods of the root of
      Angelica dahurica by the appearance and the content of active compounds. Methods:
      19 methods including natural drying in the shade, natural drying in the sun, hot
      air drying, shortwave infrared radiation drying were studied. HPLC-PDA method was
      adopted to determine the contents of coumarin compounds. GC-MS with internal
      standard method was used to determine the content of volatile oil. The appearance
      of samples was evaluated by the method of composite scores. Results: The results
      of coumarins contents showed that the natural drying in the sun was higher than
      natural drying in the shade, variable-temperature drying was the best, and the
      temperature of constant temperature drying was inversely proportional to the
      contents of coumarins. The results of volatile oils contents showed that variable
      temperature drying was the best, and the temperature of constant temperature
      drying was inversely proportional to the contents of volatile oils. The results
      of composite scores showed that hot air drying in 50 C was the best, followed by
      natural drying in the sun, natural drying in the shade and shortwave infrared
      radiation drying in 50 C. Conclusion: Therefore,considering the drying time,the
      appearance,and the content of active compounds,the hot air drying method and hot
      air machine with temperature and humidity controlled was recommend. The suitable
      parameters for the machine were that the drying temperature was 50 C,and the
      humidity was 35%. The method could provide the reference for the drying
      technology standard of roots such as Angelica dahurica.

PMID- 30203947
TI  - [Comparasion of Antis Egg-case Before and After Preparing in Reproducing Kidney
      Yang Deficiency Model Rats].
AB  - Ojective: To compare the effects of antis egg-case before and after preparing in
      reproducing kidney-Yang deficiency model rats,and to explore the best medicinal
      part of antis egg-case. Methods: Divide the rats into nine groups randomly: antis
      egg-case group, salt fried antis egg-case group, steamed antis egg-case group,
      eggs from antis egg-case group, eggs from salt fried antis egg-case group, eggs
      from steamed antis egg-case group, egg shell from antis egg-case group, egg shell
      from salt fried antis egg-case group, and egg shell from the steamed antis egg
      case group. Make kidney-Yang deficient model by giving the rats hydrocortisone.
      Two weeks later, give the rats treatment for four weeks, compare the effects of
      antis egg-case by determining the contents of NO,TSH,T3,T4,EPI,NE,17
      OH,CORT,T,E2,coefficient of thyroid, body temperature, coefficient of adrenal and
      kidney, weight and water intake. Results: Antis egg-case before and after
      preparing increased the contents of T3,T4,EPI,NE and T, increased weight, body
      temperature, coefficient of thyroid and adrenal, but reduced the contents of NO
      and E2,the coefficient of kidney and water intake were also decreased.
      Conclusion: The medicinal materials came from different medicinal parts of antis
      egg-case before and after preparing can treat the symptoms of kidney-Yang in
      different degrees. The effects of antis egg-case to treat kidney-Yang deficient
      has been strengthened after preparing, salt fried antis egg-case and eggs from
      salt fried antis egg-case played the more important role.

PMID- 30203948
TI  - [Comparative Study on Protection Effects of CCl4-Induced Acute Liver Injury of
      Different Prepared Products from Gardenia jasminoides Fruits in Rats].
AB  - Objective: To provide the experimental evidence for the appropriate selection of
      the different prepared products from Gardenia jasminoides fruits by comparing
      their protection effects on carbon tetrachloride( CCl4)-induced acute liver
      injury. Methods: The activities of ALT,AST,ADA,LDH,ALP and contents of
      PA,TP,TBIL,DBIL,TBA in serum,the activities of SOD and the content of MDA in
      liver tissue were measured in acute liver injury rats by carbon tetrachloride.
      Also the pathological changes of liver tissues were examined under microscope.
      Results: The biochemical indexes of AST,ALT,TBA,ADA,LDH and MDA were
      significantly improved in all groups of prepared products from Gardenia
      jasminoides fruits,but not SOD and ALP. The lesions of liver tissue had different
      degrees of reduction. Conclusion: The different prepared products from Gardenia
      jasminoides fruits had the effects of liver protection. The nut of Gardeniae
      Fructus was superior to the peel in enzyme decreasing and liver protection. The
      crude was superior to the stir-cooked in enzyme decreasing and liver protection.

PMID- 30203949
TI  - What Is Federalism in Healthcare For?
AB  - The Affordable Care Act (ACA) offers a window into modern American federalism-
      and modern American nationalism--in action. The ACA's federalism is defined not
      by separation between state and federal, but rather by a national structure that
      invites state-led implementation. As it turns out, that structure was only a
      starting point for a remarkably dynamic and adaptive implementation process that
      has generated new state-federal arrangements. States move back and forth between
      different structural models vis-a-vis the federal government; internal state
      politics produce different state choices; states copy, compete, and cooperate
      with each other; and negotiation with federal counterparts is a near constant.
      These characteristics have endured through the change in presidential
      administration. This Article presents the results of a study that tracked the
      details of the ACA's federalism-related implementation from 2012 to 2017. Among
      the questions that motivated the project: Does the ACA actually effectuate
      "federalism," and what are federalism's key attributes when entwined with
      national statutory implementation? A federal law on the scale of the ACA
      presented a rare opportunity to investigate implementation from a statute's very
      beginning and to provide the concrete detail often wanting in federalism
      scholarship. The findings deconstruct assumptions about federalism made by
      theorists of all stripes, from formalist to modern. Federalism's commonly invoked
      attributes--including autonomy, cooperation, experimentation, and variation--have
      not been dependent on any particular architecture of either state-federal
      separation or entanglement, even though theorists typically call on "federalism"
      to produce them. Instead, these attributes have been generated in ACA
      implementation across virtually every kind of governance model--that is,
      regardless whether states expand Medicaid; get waivers; or operate their own
      insurance exchanges or let the federal government do it for them. This makes it
      extraordinarily challenging to measure which structural arrangements are most
      "federalist," especially because the various federalism attributes are not always
      present together. The study also uncovers major theoretical difficulties when it
      comes to healthcare: Without a clear conception of the U.S. healthcare system's
      goals, how can we know which structural arrangements serve it best, much less
      whether they are working? If healthcare federalism is a mechanism to produce
      particular policy outcomes, we should determine whether locating a particular
      facet of healthcare design in the states versus the federal government positively
      affects, for example, healthcare cost, access, or quality. If, instead,
      healthcare federalism serves structural aims regardless of policy ends--for
      instance, reserving power to states in the interest of sovereignty or checks and
      balances--we should examine whether it does in fact accomplish those goals, and
      we should justify why those goals outweigh the moral concerns that animate health
      policy. The ACA did not cause this conceptual confusion, but it retained and
      built on a fragmented healthcare landscape that already was riddled with
      structural and moral compromises. This does not mean that federalism is an empty
      concept or that it does not exist in the ACA. Federalism scholars tend to argue
      for particular structural arrangements based on prior goals and values. The ACA's
      architecture challenges whether any of these goals and values are unique to
      federalism or any particular expression of it. At the same time, the ACA's
      implementation is clearly a story about state leverage, intrastate democracy, and
      state policy autonomy within, not apart from, a national statutory scheme. Its
      implementation illustrates how federalism is a proxy for many ideas and
      challenges us to ask what we are really fighting over, or seeking, when we invoke
      the concept in healthcare and beyond.

PMID- 30203951
TI  - [Identification of Chemical Constituents of the Leaves from Acanthopanax
      senticosus by UPLC-Q-TOF-MS/MS].
AB  - Objective: To analyze the chemical compositions of the leaves from Acanthopanax
      senticosus. Methods: Rapid identification of chemical constituents in the leaves
      of Acanthopanax senticosus by UPLC-Q-TOF-MS / MS. The chemical constituents were
      identified and speculated by using Peakview data processing software, the
      retention time, exact relative molecular mass, and cleavage fragments of MS / MS
      were detected. Chromatography-mass spectrometry conditions were as follows, the
      analysis was performed on Waters BEH C18column( 100 mm * 2. 1 mm,1. 7 MUm) in
      gradient elution with a mobile phase of 0. 1% formic acid aqueous solution and 0.
      1%formic acid acetonitrile, the flow rate was at 0. 3 m L / min, the data was
      collected by the negative and positive ion mode using ESI ion source. Results: 30
      compounds were identified and speculated by the standards and compounds of MS /
      MS, the references and Chemispider database. Conclusion: This method is fast,
      sensitive and comprehensive with the rapid identification of chemical
      constituents in the leaves of Acanthopanax senticosus, which will provide the
      evidences for perfecting the quality standard, and clarify the efficacy material
      base of the leaves of Acanthopanax senticosus.

PMID- 30203950
TI  - [Studies on Chemical Constituents from the Fruit of Swietenia macrophylla].
AB  - Objective: To study the chemical constituents from the fruit of Swietenia
      macrophylla. Methods: The chemical constituents were extracted and isolated by
      silica gel, Sephadex LH-20. The chemical structures of components were further
      elucidated by the physicochemical characters and MS,NMR spectral data. Results:
      17 compounds were isolated and identified as swietenine( 1),swietenine acetate(
      2),febrifugine( 3),khayasin T( 4),3-O-tigloyl-6-O-acetylswietenolide( 5),3-O
      tigloylswietenolide( 6),3,6-O,O-diacetylswietenolide( 7),fissinolide( 8),3-O
      acetylswietenolide( 9), proceranolide( 10),swietenolide( 11),swietemahonin E(
      12),swietemahonin F( 13),7-deacetoxy-7-oxogedunin( 14),secomahoganin(
      15),altissimanin B( 16),ororatone( 17). Conclusion: Compounds3,5,8 ~ 10,16,17 are
      isolated from this plant for the first time.

PMID- 30203952
TI  - [Chemical Constituents of the Aerial Parts from Plumbago zeylanica].
AB  - Objective: To study the anti-oxidative constituents of the aerial parts of
      Plumbago zeylanica. Methods: The ethanol extract of Plumbago zeylanica was
      separated and purified by various chromatographic techniques. On the basis of
      various spectroscopic data, the structures of isolated compounds were elucidated.
      ABTS+radical scavenging were carried out in antioxidant activity evaluation of
      the isolated compounds. Results: Eleven compounds were isolated and identified as
      cis-isoshinanolone-4-O-beta-D-glucopyranoside( 1),tachioside( 2),2,6-dimethoxy-p
      hydroquinone-1-O-beta-D-glucopyranoside( 3),3-( beta-D-glucopyranosyloxy)-4
      methoxybenzoic acid( 4),3'-O-beta-D-glucopyranosyloxy-plumbagic acid( 5),3'-O
      beta-D-glucopyranosyloxy-plumbagic acid methyl ester( 6),plumbagic acid(
      7),plumbagine A( 8),plumbagine C( 9),syringate-4-O-beta-D-glucopyranoside( 10)
      and 2-methyl-5-hydroxychromone( 11). Compounds 2,3,and5 displayed significant
      scavenging effect on ABTS+. Conclusion: Compounds 1 ~ 4,10,11 are obtained from
      this plant for the first time. Compounds 2,3,and 5 show significant anti
      oxidative effects.

PMID- 30203953
TI  - [Chemical Constituents from A Taditional Mongolian Medicine Clematis
      aethusifolia].
AB  - Objective: To investigate the chemical constituents of Clematis aethusifolia,a
      traditional Mongolian medicine for resolving hard lump. Methods: Bioactive guided
      isolation and purification of Clematis aethusifolia was performed by normal and
      reverse phase column chromatography, Sephadex LH-20 and preparation HPLC. The
      structures were identified by 1D,2D-NMR and MS spectral analysis and comparison
      with literature data. Cytotoxicity of compounds were determined by CCK-8 cell
      staining method for detecting growth inhibition to five kinds of human solid
      tumor cell lines. Results: Eight compounds were isolated and identified as
      vanillicacid( 1),protocatechuic acid( 2),( +)-pinoresinol diglucoside( 3),( +)
      pinoresinol-4'-O-beta-D-glucopyranoside( 4),( +)-syringaresinol-4'-O-beta
      Dglucopyranoside( 5),7,9,9'-trihydroxy-3,3'-dimethoxy-8-O-4'-neolignan-4-O-beta-D
      glucopyranoside( 6),butyl-beta-D-fructopyranoside( 7),butyl-beta-D
      fructofuranoside( 8). Compounds 2,8 showed strong cytotoxic activity. Conclusion:
      All the compounds are isolated from this plant for the first time, Results: Eight
      compounds were isolated and identified as vanillicacid( 1), protocatechuic acid(
      2),( +)-pinoresinol diglucoside( 3),( +)-pinoresinol-4'-O-beta-D-glucopyranoside(
      4),( +)-syringaresinol-4'-O-beta-Dglucopyranoside( 5),7,9,9'-trihydroxy-3,3'
      dimethoxy-8-O-4'-neolignan-4-O-beta-D-glucopyranoside( 6),butyl-beta-D
      fructopyranoside( 7),butyl-beta-D-fructofuranoside( 8). Compounds 2,8 showed
      strong cytotoxic activity. compounds 3,6 ~ 8 are isolated from Clematis genus for
      the first time, compounds 6 and 8 are isolated from Ranunculaceae family for the
      first time. Compounds 2,8 may be the effective components in Clematis
      aethusifolia.

PMID- 30203954
TI  - In Situ Synthesis of Ultrathin ZIF-8 Film-Coated MSNs for Codelivering Bcl 2
      siRNA and Doxorubicin to Enhance Chemotherapeutic Efficacy in Drug-Resistant
      Cancer Cells.
AB  - Multiple drug resistance is a persistent obstacle for efficient chemotherapy of
      cancer. Herein, we report a novel drug delivery platform. A zeolitic imidazole
      framework-8 (ZIF-8) film with a few nanometer thickness was in situ synthesized
      on the surface of carboxylated mesoporous silica (MSN-COOH) nanoparticles (NPs)
      for pore blocking and efficient loading of small interfering RNAs to fabricate a
      pH-responsive drug delivery system. The ZIF-8 film could convert the charge of
      MSN-COOH from negative to positive for efficient loading of siRNA via
      electrostatic interactions and protect siRNA from nuclease degradation. The
      positively charged ZIF-8 film facilitates cellular uptake and endo-lysosome
      escape of the NPs. In addition, the ultrathin ZIF-8 film can decompose in the
      acidic endo-lysosome and trigger the intracellular release of siRNAs and
      chemotherapeutic drugs, leading to a significantly enhanced chemotherapeutic
      efficacy for multidrug-resistant cancer cells including MCF-7/ADR and SKOV-3/ADR
      cells as demonstrated by the confocal laser scanning microscopy image, cell
      viability assay, Annexin V&PI staining, and flow cytometry. This approach
      provides a promising strategy for pH-triggered, stimuli-responsive delivery of
      nucleic acid drugs and chemotherapeutic agents with remarkably enhanced
      chemotherapeutic efficacy.

PMID- 30203955
TI  - Reversible Ultralong Organic Phosphorescence for Visual and Selective Chloroform
      Detection.
AB  - Volatile organic compounds (VOCs) are widespread in our daily life and greatly
      harmful to human health, as well as to the environment. To date, it remains a
      formidable challenge to develop a highly sensitive visual system for selective
      detection of VOCs. Herein, we report on a metal-free organic molecule of 2,4
      di(10 H-phenothiazin-10-yl)-1,3,5-triazine (TDP) with ultralong organic
      phosphorescence (UOP) feature as a visible chemical probe for chloroform
      detection. In the pristine solid state, this phosphor shows a green UOP with a
      lifetime of 56 ms after the removal of excitation light source; however, the UOP
      greatly diminishes when fumed with chloroform, which is ascribed to the variation
      in both radiative and nonradiative transitions in crystal with embedded
      chloroform. Remarkably, TDP materials demonstrate great potential as a visual
      chemical probe for chloroform, showing high sensitivity, excellent selectivity,
      and good repeatability. The limitation for chloroform detection is as low as 5
      ppm. Combining experimental data and theoretical calculations, it is reasoned
      that the space confinement via intermolecular interactions between chloroform and
      TDP molecules play a vital role for high selectivity of chloroform detection.
      These results pave the way toward expanding the scope of organic luminogens with
      UOP as well as their applications.

PMID- 30203956
TI  - Biomimetic Shells Endow Sub-50 nm Nanoparticles with Ultrahigh Paclitaxel
      Payloads for Specific and Robust Chemotherapy.
AB  - Poor loading capacity and nonspecific tumor accumulation of current drug delivery
      system remain the critical challenges that prevent nanomedicine from maximizing
      therapeutic efficacy in cancer treatment. Herein, poly(ester amide) polymers
      composed of cationic and hydrophobic segments were formulated with a
      paclitaxel/human serum albumin (PTX/HSA) complex, as well as free PTX, to
      construct a core-shell nanoparticle (NP) platform with the interior
      simultaneously reserving PTX and PTX/HSA complex, while the exterior absorbing
      the PTX/HSA complex. Following systematic screening, the optimized NPs, namely,
      APP1i@e NPs, exhibited small particle size (43.95 nm), maximal PTX loading
      (42.23%), excellent dynamic stability (at least 1 week), and acid-triggered
      release. In vitro results showed that after being trafficked through caveolae
      mediated endocytosis, APP1i@e NPs successfully escaped from endo-/lysosomes and
      then rapidly released cargos in the acidic cytosol, which continued to enhance
      cytotoxicity by mitochondrial control of apoptosis and suppression of microtubule
      dynamics. Longer circulation time and superior targeting efficiency post
      intravenous injection confirmed that surface PEGylation imparted APP1i@e NPs with
      the ability to control their pharmacokinetics and biodistribution. The biomimetic
      shell design with HSA, which enlarged PTX stock and improved biosafety, made
      APP1i@e NPs more suitable for in vivo applications. Furthermore, in vivo safety
      and efficacy demonstrated that APP1i@e NPs effectively inhibited the growth of
      ovarian xenograft tumors, whereas significantly avoiding toxic issues associated
      with PTX. APP1i@e NPs with surface PEG coating and biomimetic HSA design,
      therefore, may provide a remarkable improvement in the therapeutic index of
      taxanes used in the clinic.

PMID- 30203957
TI  - Enhancing the Mechanical Properties of Glassy Nanocomposites by Tuning Polymer
      Molecular Weight.
AB  - The addition of nanoparticles to a polymer matrix is a well-known process to
      improve the mechanical properties of polymers. Many studies of mechanical
      reinforcement in polymer nanocomposites (PNCs) focus on rubbery matrices;
      however, much less effort concentrates on the factors controlling the mechanical
      performance of the technologically important glassy PNCs. This paper presents a
      study of the effect of the polymer molecular weight (MW) on the overall
      mechanical properties of glassy PNCs with attractive interaction by using
      Brillouin light scattering. We found that the mechanical moduli (bulk and shear)
      have a nonmonotonic dependence on MW that cannot be predicted by simple rule of
      mixtures. The moduli increase with increasing MW up to 100 kg/mol followed by a
      drop at higher MW. We demonstrate that the change in the mechanical properties of
      PNCs can be associated with the properties of the interfacial polymer layer. The
      latter depend on the interfacial chain packing and stretching, as well as polymer
      bridging, which vary differently with the MW of the polymer. These competing
      contributions lead to the observed nonmonotonic variations of the glassy PNC
      moduli with MW. Our work provides a simple, cost-effective, and efficient way to
      control the mechanical properties of glassy PNCs by tuning the polymer chain
      length. Our finding can be beneficial for the rational design of PNCs with
      desired mechanical performance.

PMID- 30203958
TI  - Overcoming Interfacial Scaling Using Engineered Nanocelluloses: A QCM-D Study.
AB  - Nucleation of sparingly soluble species, such as the inorganic salts of calcium,
      magnesium, and phosphorous, followed by their growth at solid-liquid interfaces
      has turned into a major concern in water-based industries. Increased resistance
      against heat, mass, and momentum transfer is the main drawback of the so-called
      scaling phenomenon. Although phosphorous-, nitrogen-, and sulfur-based
      antiscaling macromolecules offer adequate antiscaling performance, their
      potential negative environmental impacts render them less desirable. Despite
      recent efforts in developing green antiscalants, there has been no promising
      green solution based on biomass due to its chemical inertness. Here, we use
      quartz crystal microbalance with dissipation monitoring (QCM-D) to evaluate the
      real-time performance of an emerging family of nanoengineered anionic hairy
      cellulose crystals, bearing dicarboxylated amorphous cellulose chains, with a
      charge density of more than 5.5 mequiv per g, in preventing the nucleation and
      growth of calcium carbonate, the most common industrial scale. Remarkably, a
      CaCO3 mass deposition rate ~0 (complete scale inhibition) is obtained when less
      than 10 ppm of the hairy nanocellulose is added to an already scaled surface
      under a harsh supersaturated condition at 50  degrees C. Motivated by their
      threshold antiscaling effect, we show that coating planar silica surfaces with
      hairy nanocelluloses may result in scale-resistant interfaces. This research
      envisions how engineered hairy nanocelluloses may have practical implications for
      developing scale-resistant interfaces based on the most abundant biopolymer in
      the world.

PMID- 30203959
TI  - Enzymatically Disulfide-Crosslinked Chitosan/Hyaluronic Acid Layer-by-Layer Self
      Assembled Microcapsules for Redox-Responsive Controlled Release of Protein.
AB  - Disulfide-crosslinked hollow polyelectrolyte microcapsules composed of thiolated
      chitosan (CS-SH) and hyaluronic acid (HA-SH) were prepared by combining the layer
      by-layer (LBL) technique and horseradish peroxidase (HRP)-mediated oxidative
      cross-linking reaction in mild conditions. FITC-dextran-doped CaCO3 microspheres
      were used as template core and removed after LBL depositing CS-SH and HA-SH on
      the surface. The disulfide-crosslinked (CS/HA) microcapsules were readily
      fabricated by HRP-mediated oxidative coupling of the thiol groups in CS/HA shell
      layer in the presence of HRP (10 units/mL) and Tyramine hydrochloride (Tyr, 35
      mmol/L). The kinetics of enzymatic disulfide-crosslinking reaction was
      investigated through the real-time monitoring of the consumption of thiol groups
      by UV absorption spectra. It found that the formation of disulfide linkages by
      the enzymatic thiol oxidation reaction showed a gradual acceleration. The
      disulfide-crosslinked CS/HA hydrogel were rapidly formed in gelation time between
      approximately 17 and 30 min, which were dependent on the concentrations of HRP
      and Tyr. The disulfide linkages endowed the microcapsule-enhanced physical
      stability and low permeability under physiological conditions and redox
      responsive degradability in reducing environments. The structural stability of
      disulfide-crosslinked (CS/HA) microcapsules was visualized by confocal laser
      scanning microscopy in phosphate-buffered saline containing 5.0 mmol/L
      dithiothreitol (DTT) to evaluate the redox-responsive disassembly process. Redox
      responsive controlled release of encapsulated FITC-dextran from the disulfide
      crosslinked (CS/HA) microcapsules were obtained. The release profiles of FITC
      dextran could be manipulated by controlling the shell thickness and the
      concentration of DTT. The conformational stability analyses and more than 94%
      esterase activity of released bovine serum albumin (BSA) from (CS/HA)
      microcapsules conformed that the structural integrity and bioactivity were well
      preserved during the encapsulation and release process. The microcapsules
      exhibited excellent cytocompatibility for HEK 293 cells up to a concentration of
      1.0 mg/mL. The microcapsules efficiently delivered loaded FITC-BSA into HeLa
      cells and released the protein in the reducing cytosol. This study proposed a
      novel approach for producing disulfide-crosslinked microcarriers for
      intracellular delivery and redox-responsive controlled release of protein.

PMID- 30203960
TI  - Direct Determination of Aerosol pH: Size-Resolved Measurements of Submicrometer
      and Supermicrometer Aqueous Particles.
AB  - Measuring the acidity of atmospheric aerosols is critical, as many key multiphase
      chemical reactions involving aerosols are highly pH-dependent. These reactions
      impact processes, such as secondary organic aerosol (SOA) formation, that impact
      climate and health. However, determining the pH of atmospheric particles, which
      have minute volumes (10-23-10-18 L), is an analytical challenge due to the
      nonconservative nature of the hydronium ion, particularly as most chemical
      aerosol measurements are made offline or under vacuum, where water can be lost
      and acid-base equilibria shifted. Because of these challenges, there have been no
      direct methods to probe atmospheric aerosol acidity, and pH has typically been
      determined by proxy/indirect methods, such as ion balance, or thermodynamic
      models. Herein, we present a novel and facile method for direct measurement of
      size-resolved aerosol acidity from pH 0 to 4.5 using quantitative colorimetric
      image processing of cellular phone images of (NH4)2SO4-H2SO4 aqueous aerosol
      particles impacted onto pH-indicator paper. A trend of increasing aerosol acidity
      with decreasing particle size was observed that is consistent with spectroscopic
      measurements of individual particle pH. These results indicate the potential for
      direct measurements of size-resolved atmospheric aerosol acidity, which is needed
      to improve fundamental understanding of pH-dependent atmospheric processes, such
      as SOA formation.

PMID- 30203961
TI  - New Azo-DMOF-1 MOF as a Photoresponsive Low-Energy CO2 Adsorbent and Its
      Exceptional CO2/N2 Separation Performance in Mixed Matrix Membranes.
AB  - A new generation-2 light-responsive metal-organic framework (MOF) has been
      successfully synthesized using Zn as the metal source and both 2-phenyldiazenyl
      terephthalic acid and 1,4-diazabicyclo[2.2.2]octane (DABCO) as the ligands. It
      was found that Zn-azo-dabco MOF (Azo-DMOF-1) exhibited a photoresponsive CO2
      adsorption both in static and dynamic condition because of the presence of
      azobenzene functionalities from the ligand. Further application of this MOF was
      evaluated by incorporating it as a filler in a mixed matrix membrane for CO2/N2
      gas separation. Matrimid and polymer of intrinsic microporosity-1 (PIM-1) were
      used as the polymer matrix. It was found that Azo-DMOF-1 could enhance both the
      CO2 permeability and selectivity of the pristine polymer. In particular, the Azo
      DMOF-1-PIM-1 composite membranes have shown a promising performance that
      surpassed the 2008 Robeson Upper Bound.

PMID- 30203962
TI  - Discovering Selective Binders for Photoswitchable Proteins Using Phage Display.
AB  - Nature provides an array of proteins that change conformation in response to
      light. The discovery of a complementary array of proteins that bind only the
      light-state or dark-state conformation of their photoactive partner proteins
      would allow each light-switchable protein to be used as an optogenetic tool to
      control protein-protein interactions. However, as many photoactive proteins have
      no known binding partner, the advantages of optogenetic control-precise spatial
      and temporal resolution-are currently restricted to a few well-defined natural
      systems. In addition, the affinities and kinetics of native interactions are
      often suboptimal and are difficult to engineer in the absence of any structural
      information. We report a phage display strategy using a small scaffold protein
      that can be used to discover new binding partners for both light and dark states
      of a given light-switchable protein. We used our approach to generate binding
      partners that interact specifically with the light state or the dark state
      conformation of two light-switchable proteins: PYP, a test case for a protein
      with no known partners, and AsLOV2, a well-characterized protein. We show that
      these novel light-switchable protein-protein interactions can function in living
      cells to control subcellular localization processes.

PMID- 30203963
TI  - Light-Triggered Drug Release from 3D-Printed Magnetic Chitosan Microswimmers.
AB  - Advances in design and fabrication of functional micro/nanomaterials have sparked
      growing interest in creating new mobile microswimmers for various healthcare
      applications, including local drug and other cargo ( e. g., gene, stem cell, and
      imaging agent) delivery. Such microswimmer-based cargo delivery is typically
      passive by diffusion of the cargo material from the swimmer body; however,
      controlled active release of the cargo material is essential for on-demand,
      precise, and effective delivery. Here, we propose a magnetically powered, double
      helical microswimmer of 6 MUm diameter and 20 MUm length that can on-demand
      actively release a chemotherapeutic drug, doxorubicin, using an external light
      stimulus. We fabricate the microswimmers by two-photon-based 3D printing of a
      natural polymer derivative of chitosan in the form of a magnetic polymer
      nanocomposite. Amino groups presented on the microswimmers are modified with
      doxorubicin by means of a photocleavable linker. Chitosan imparts the
      microswimmers with biocompatibility and biodegradability for use in a biological
      setting. Controlled steerability of the microswimmers is shown under a 10 mT
      rotating magnetic field. With light induction at 365 nm wavelength and 3.4 * 10-1
      W/cm2 intensity, 60% of doxorubicin is released from the microswimmers within 5
      min. Drug release is ceased by controlled patterns of light induction, so as to
      adjust the desired release doses in the temporal domain. Under physiologically
      relevant conditions, substantial degradation of the microswimmers is shown in 204
      h to nontoxic degradation products. This study presents the combination of light
      triggered drug delivery with magnetically powered microswimmer mobility. This
      approach could be extended to similar systems where multiple control schemes are
      needed for on-demand medical tasks with high precision and efficiency.

PMID- 30203964
TI  - Synthetic Phosphorus Metabolic Pathway for Biosafety and Contamination Management
      of Cyanobacterial Cultivation.
AB  - Recent progress in genetic engineering and synthetic biology have greatly
      expanded the production capabilities of cyanobacteria, but concerns regarding
      biosafety issues and the risk of contamination of cultures in outdoor culture
      conditions remain to be resolved. With this dual goal in mind, we applied the
      recently established biological containment strategy based on phosphite (H3PO3,
      Pt) dependency to the model cyanobacterium Synechococcus elongatus PCC 7942 ( Syn
      7942). Pt assimilation capability was conferred on Syn 7942 by the introduction
      of Pt dehydrogenase (PtxD) and hypophosphite transporter (HtxBCDE) genes that
      allow the uptake of Pt, but not phosphate (H3PO4, Pi). We then identified and
      disrupted the two indigenous Pi transporters, pst (Synpcc7942_2441 to 2445) and
      pit (Synpcc7942_0184). The resultant strain failed to grow on any media
      containing various types of P compounds other than Pt. The strain did not yield
      any escape mutants for at least 28 days with a detection limit of 3.6 * 10-11 per
      colony forming unit, and rapidly lost viability in the absence of Pt. Moreover,
      growth competition of the Pt-dependent strain with wild-type cyanobacteria
      revealed that the Pt-dependent strain could dominate in cultures containing Pt as
      the sole P source. Because Pt is rarely available in aquatic environments this
      strategy can contribute to both biosafety and contamination management of
      genetically engineered cyanobacteria.

PMID- 30203965
TI  - Discovery of Butyrylcholinesterase-Activated Near-Infrared Fluorogenic Probe for
      Live-Cell and In Vivo Imaging.
AB  - Butyrylcholinesterase (BChE) is widely distributed in various tissues and highly
      implicated in several important human diseases, especially Alzheimer's disease
      (AD). However, the role of BChE in AD is still controversial, which may be
      partially attributed to the lack of a direct tool for real-time and noninvasive
      monitoring of BChE in in vivo. Here, we report three rationally designed near
      infrared fluorogenic probes that possess excellent discrimination for
      butyrylcholinesterase (BChE) over the related enzyme acetylcholinesterase (AChE).
      The refined probe, BChE-NIRFP, not only functions as an exquisite substrate for
      BChE in in vitro assays but also represents a superb "signal-on" imaging tool to
      real-time track BChE levels in human cells, zebrafish, and a mouse model of AD. A
      further application of BChE-NIRFP to identify the cellular mechanism reveals that
      Abeta fibrils and insulin resistance may be important contributors to the
      abnormally elevated BChE levels observed during AD progression. Based on the
      results from the present study, this new probe is a valuable tool for basic and
      clinical research designed to obtain a complete understanding of the
      physiological roles of BChE in diverse human diseases, particularly AD.

PMID- 30203966
TI  - Correction to An Alkaloid from Scorpion Venom: Chemical Structure and Synthesis.

PMID- 30203967
TI  - Combined Effects of Dust and Dietary Exposure of Occupational Workers and Local
      Residents to Short- and Medium-Chain Chlorinated Paraffins in a Mega E-Waste
      Recycling Industrial Park in South China.
AB  - Four types of dust samples and nine categories of locally produced staple foods
      were collected from a mega e-waste recycling industrial park and its surrounding
      regions, and simultaneously analyzed for short-chain and medium-chain chlorinated
      paraffins (CPs) to estimate dust and dietary exposure and their combined effects
      on occupational workers and local residents. All samples related to e-waste
      activities contained considerably high concentrations of CPs. The highest dust
      concentration was found in e-waste workshops. CPs were highly accumulated in
      local plant and animal origin foods, most markedly in fish, vegetables, and rice.
      The main contribution to CP intake under a median exposure scenario was from the
      diet, and vegetables, fish, and rice were the three largest dietary intake
      sources. Only the combined dust and food exposure from the present study has
      approached or even exceeded the highest tolerable daily intake (TDI) set up by
      the International Program on Chemical Safety (IPCS). However, due to lack of
      official threshold values for CP exposure on adverse human health, there are
      limitations on accurate risk assessment. Considering the presence of other
      exposure pathways, CPs' endocrine disrupter properties, as well as the
      multicomponent chemical "cocktails" effects, potential high risks from CP
      exposure may be posed to e-waste workers and local residents.

PMID- 30203968
TI  - Decreasing Vanadium Footprint of Bunker Fuel Emissions.
AB  - The Interagency Monitoring of Protected Visual Environments (IMPROVE) network
      measures the chemical composition of atmospheric particulate matter at over 160
      locations throughout the United States. As part of the routine quality control
      process, we noted decreases in the network-wide vanadium (V) and nickel (Ni)
      concentrations in 2015 relative to the previous years. Enriched V and Ni with
      respect to soil are indicative of heavy fuel oil burning and are often used as
      tracers for emissions from marine vessels. Multiple regulations on the fuel used
      by marine vessels were implemented in North America since 2010, and the most
      sweeping regulation was implemented at the start of 2015. The 2015 regulations
      reduced the allowable fuel oil sulfur concentrations within the North America
      Emissions Control Area from 1.0% to 0.1% to reduce the environmental and human
      health impacts of sulfates. As a side effect, these requirements economically
      favored fuels with lower V and Ni concentrations. The atmospheric concentrations
      of V and Ni decreased markedly at many IMPROVE monitoring sites, particularly
      sites near major ports. Between 2011 and 2015, annual mean V concentrations
      measured on IMPROVE samples collected near the ports of Seattle, Washington and
      New Orleans, Louisiana decreased by 35% and 85%, respectively. These decreases
      have brought the coastal V and Ni concentrations much closer to those measured
      far inland.

PMID- 30203969
TI  - Benefit of Hydrophilicity for Adsorption of Methyl Orange and Electro-Fenton
      Regeneration of Activated Carbon-Polytetrafluoroethylene Electrodes.
AB  - Activated carbon (AC)-polytetrafluoroethylene (PTFE) electrodes were prepared and
      applied for methyl orange (MO) adsorption and electro-Fenton regeneration. The
      addition of PTFE to AC significantly decreased the hydrophilicity, which in turn,
      decreased both the amount of MO adsorbed and the regeneration efficiency. With
      the minimum amount of binder (a 7:1 mass ratio of AC to binder), the MO
      adsorption was 176 mg g-1. The amount adsorbed decreased to 23 mg g-1 for the
      electrode with a 1:1 mass ratio of AC to binder. For these ratios, the
      regeneration efficiencies were 81% and 49%, respectively. The adsorption kinetics
      were well fit by a Weber-Morris model. The diffusion rate constants obtained from
      this model were linearly related to the hydrophilicity of the electrode, i.e.,
      the higher the hydrophilicity the higher the adsorption rate. Based on the
      results, an adsorption capacity >50 mg g-1 in 8 h with a regeneration efficiency
      of >70% at cathodic potential of -0.8 V (vs Ag/AgCl) can be obtained if the
      contact angle of water on the electrodes is lower than 90 degrees .

PMID- 30203970
TI  - Improvement of Multiple-Stress Tolerance and Ethanol Production in Yeast during
      Very-High-Gravity Fermentation by Supplementation of Wheat-Gluten Hydrolysates
      and Their Ultrafiltration Fractions.
AB  - The effects of wheat-gluten hydrolysates (WGH) and their ultrafiltration
      fractions on multiple-stress tolerance and ethanol production in yeast during
      very-high-gravity (VHG) fermentation were examined. The results showed that WGH
      and WHG-ultrafiltration-fraction supplementations could significantly enhance the
      growth and viability of yeast and further improve the tolerance of yeast to
      osmotic stress and ethanol stress. The addition of MW < 1 kDa fractions led to
      51.08 and 21.70% enhancements in cell-membrane integrity, 30.74 and 10.43%
      decreases in intracellular ROS accumulation, and 34.18 and 26.16% increases in
      mitochondrial membrane potential (DeltaPsim) in yeast under osmotic stress and
      ethanol stress, respectively. Moreover, WGH and WHG-ultrafiltration-fraction
      supplementations also improved the growth and ethanol production of yeast during
      VHG fermentation, and supplementation with the <1 kDa fraction resulted in a
      maximum biomass of 16.47 g/L dry cell and an ethanol content of 18.50% (v/v)
      after VHG fermentation.

PMID- 30203971
TI  - LiSr2SiO4H, an Air-Stable Hydride as Host for Eu(II) Luminescence.
AB  - LiSr2SiO4H is synthesized by solid-state reaction of LiH and alpha-Sr2SiO4. It
      crystallizes in space group P21/ m ( a = 658.63(4) pm, b = 542.36(3) pm, c =
      695.01(4) pm, beta = 112.5637(9) degrees ) as proven by X-ray and neutron
      diffraction, is isotypic to LiSr2SiO4F, and exhibits isolated SiO4 tetrahedra.
      Hydride anions are located in Li2Sr4 octahedra, which share faces to form
      columns, with H-H distances of 271.18(2) pm. NMR, IR, and Raman spectroscopy,
      density measurements, elemental analysis, and theoretical calculations confirm
      these results. Despite its hydridic nature, it is stable in air up to 550 K. When
      doped with europium, it emits bright yellow-green light with an intensity maximum
      at 560 nm for LiSr1.98Eu0.02SiO4H. Even after treatment in water for several
      hours, the solid shows luminescence. The broad emission peak is attributed to the
      allowed 4f65d -> 4f7 transition of divalent europium. LiSr2SiO4H is the first
      silicate hydride, a class of compounds that might have potential as host for
      luminescent materials.

PMID- 30203972
TI  - Anti-EGFR Affibodies with Site-Specific Photo-Cross-Linker Incorporation Show
      Both Directed Target-Specific Photoconjugation and Increased Retention in Tumors.
AB  - A significant challenge for solid tumor treatment is ensuring that a sufficient
      concentration of therapeutic agent is delivered to the tumor site at doses that
      can be tolerated by the patient. Biomolecular targeting can bias accumulation in
      tumors by taking advantage of specific interactions with receptors overexpressed
      on cancerous cells. However, while antibody-based immunoconjugates show high
      binding to specific cells, their low dissociation constants ( KD) and large
      Stokes radii hinder their ability to penetrate deep into tumor tissue, leading to
      incomplete cell killing and tumor recurrence. To address this, we demonstrate the
      design and production of a photo-cross-linkable affibody that can form a covalent
      bond to epidermal growth factor receptor (EGFR) under near UV irradiation. Twelve
      cysteine mutations were created of an EGFR affibody and conjugated with maleimide
      benzophenone. Of these only one exhibited photoconjugation to EGFR, as
      demonstrated by SDS-PAGE and Western blot. Next this modified affibody was shown
      to not only bind EGFR expressing cells but also show enhanced retention in a 3D
      tumor spheroid model, with minimal loss up to 24 h as compared to either
      unmodified EGFR-binding affibodies or nonbinding, photo-cross-linkable
      affibodies. Finally, in order to show utility of photo-cross-linking at
      clinically relevant wavelengths, upconverting nanoparticles (UCNPs) were
      synthesized that could convert 980 nm light to UV and blue light. In the presence
      of UCNPs, both direct photoconjugation to EGFR and enhanced retention in tumor
      spheroids could be obtained using near-infrared illumination. Thus, the
      photoactive affibodies developed here may be utilized as a platform technology
      for engineering new therapy conjugates that can penetrate deep into tumor tissue
      and be retained long enough for effective tumor therapy.

PMID- 30203973
TI  - Theoretical Insights into the Interaction Mechanisms between Nitric Acid and
      Nitrous Oxide Initiated by an Excess Electron.
AB  - Nitric acid (HNO3) and nitrous oxide (N2O) play an important role in the
      atmospheric chemistry in regulating the global environment and climate changes.
      In this study, the interaction mechanisms between them have been systematically
      investigated before and after the electron capture employing the density
      functional theory in combination with the AIM, NBO, and ab initio molecular
      dynamics calculations. It was found that HNO3 and N2O can form transient
      complexes through intermolecular H-bonds. HNNO, OH, and NO2 free radicals can be
      produced after the electron capture of the formed complexes, providing an
      alternative source of these radicals in the atmosphere. The present results not
      only can provide new insights into the transformation of the HNO3 and N2O
      atmospheric species but also can enable us to better understand the potential
      role of the free electron in the atmosphere.

PMID- 30203974
TI  - Glyphosate Resistance Technology Has Minimal or No Effect on Maize Mineral
      Content and Yield.
AB  - Controversy continues to exist regarding whether the transgene for glyphosate
      resistance (GR) and/or glyphosate applied to GR crops adversely affect plant
      mineral content. Field studies were conducted in 2013 and 2014 in Stoneville, MS
      and Urbana, IL to examine this issue in maize. At each location, the experiment
      was conducted in fields with no history of glyphosate application and fields with
      several years of glyphosate use preceding the study. Neither glyphosate nor the
      GR transgene affected yield or mineral content of leaves or seed, except for
      occasional (<5%) significant effects that were inconsistent across minerals,
      treatments, and environments. Glyphosate and AMPA (aminomethylphosphonic acid), a
      main degradation product of glyphosate, were found in leaves from treated plants,
      but little or no glyphosate and no AMPA was found in maize seeds. These results
      show that the GR transgene and glyphosate application, whether used for a single
      year or several years, have no deleterious effect on mineral nutrition or yield
      of GR maize.

PMID- 30203975
TI  - Elucidating the Binding Modes of N-Heterocyclic Carbenes on a Gold Surface.
AB  - Tuning the binding mode of N-heterocyclic carbenes on metal surfaces is crucial
      for the development of new functional materials. To understand the impact of
      alkyl side groups on the formation of NHC species at the Au(111) surface, we
      combined scanning tunneling microscopy, X-ray photoelectron spectroscopy, and
      density functional theory calculations. We reveal two significantly different
      binding modes depending on the alkyl chain length. In the case of a short alkyl
      substituent, an up-standing configuration with one Au adatom is preferred,
      whereas the longer alkyl groups result exclusively in NHC-Au-NHC complexes lying
      flat on the surface. Our study highlights how well-defined structural
      modifications of NHCs allow for controlling the local binding motif on surfaces,
      which is important to design designated catalytic sites at interfaces.

PMID- 30203976
TI  - Second-Harmonic Scattering in Layered Double Hydroxide Colloids: A Microscopic
      View of Adsorption and Intercalation.
AB  - The interaction of methyl orange dye with a layered double hydroxide colloidal
      material is investigated using real-time polarization-resolved second-harmonic
      scattering (SHS). Interlayer charge compensating anion exchange is studied from
      initial carbonate or nitrate anions to methyl orange negatively charged dye. A
      theoretical model, taking into account the field retardation effect, is presented
      to simulate the polarization-resolved SHS experiments. Various geometrical dye
      configurations inside or around the host material have been modeled. A comparison
      with the experimental data permits to give a microscopic description of the dye
      organization and its time evolution during the intercalation process in the
      material.

PMID- 30203977
TI  - Structural Colored Balloon Composed of Temperature-Responsive Polymers Showing
      LCST Behavior.
AB  - Structural colored balloons (SCBs) consisting of polymer thin film developed
      structural color by thin-layer interference on the shell. Thermoresponsive SCBs
      were prepared with poly(diethylene glycol monomethyl ether methacrylate)- co
      poly( N-phenylacrylamide), which shows lower critical solution temperature (LCST)
      behavior. When cooling gelatin aqueous solution in which osmotic pressure was not
      operated, only hydration of the copolymer progressed due to LCST transition. The
      optical path length of the SCB increased due to swelling by water and
      subsequently decreased due to dissolution. The structural color changed according
      to the change in optical path length. In cold pure water, in addition to the
      hydration, osmotic pressure was operated to induce an influx of the outer solvent
      and the resulting diameter change also affected the shell thickness. The
      structural color change was analyzed to reveal that the dissolution of the
      polymer had significant effect on the developed structural color.

PMID- 30203978
TI  - Nickel-Catalyzed Hydrogen-Borrowing Strategy for alpha-Alkylation of Ketones with
      Alcohols: A New Route to Branched gem-Bis(alkyl) Ketones.
AB  - The alpha-alkylation of ketones using an earth-abundant and nonprecious NiBr2/L1
      system is reported. This nickel-catalyzed reaction could be performed in gram
      scale and successfully applied in the synthesis of donepezil (Alzheimer's drug)
      and functionalization of steroid hormones and fatty acid derivatives. Synthesis
      of N-heterocycles, methylation of ketones, and one-pot double alkylation to bis
      hetero aryl ketones using two different alcohols with a single catalyst broadens
      the scope of the catalytic protocol. Preliminary mechanistic studies using
      defined Ni-H species and deuterium-labeling experiments established the
      participation of the borrowing-hydrogen strategy.

PMID- 30203979
TI  - Tuning Ice Nucleation and Propagation with Counterions on Multilayer Hydrogels.
AB  - Ice formation on solid surfaces includes heterogeneous ice nucleation and ice
      propagation processes. However, no study has been focused on tuning of both ice
      nucleation and ice propagation via a simple anti-icing coating method. In this
      work, we have prepared multilayer hydrogels based on simple layer-by-layer (LBL)
      deposition approach and discover the ion-specific effect on both ice nucleation
      and ice propagation. A large ice nucleation temperature window of 11  degrees C
      is controlled via changing different counterions; meanwhile, the differences in
      ice propagation time can be tuned up to 4 orders of magnitude. Through
      synergistically controlling of ice nucleation and propagation delay times, we can
      tune the freezing delay time of water droplets on multilayer hydrogel surfaces up
      to 3 orders of magnitude via changing various counterions. Considering the
      application requirements, these multilayer hydrogels are stable under different
      conditions and can be coated on various materials without destroying the existing
      surface. This new insight can inspire the design of anti-icing surfaces based on
      regulating both ice nucleation and ice propagation.

PMID- 30203980
TI  - Polycyclic Indoline Derivatives by Dearomatizing Anionic Cyclization of Indole
      and Tryptamine-Derived Ureas.
AB  - The base-promoted dearomatizing cyclization of anionic indole-containing urea
      derivatives provided tri- or tetracyclic indoline-containing scaffolds from
      lithiated urea intermediates. 3-Substituted indoles, including tryptamine
      derivatives, generally underwent the reaction in high yield and with excellent
      diastereoselectivity. In situ IR spectroscopy suggests a deprotonation
      carbolithiation-reprotonation mechanism.

PMID- 30203981
TI  - Intramolecular Umpolung Allylation of Imines.
AB  - An intramolecular umpolung allylation of imines is reported. This reaction occurs
      via the intermediacy of 2-azaallyl anions. It could proceed either under
      transition-metal-catalyzed conditions or under transition-metal-free conditions.
      Importantly, this approach afforded trans-3-vinyl-4-aminochromanes with high
      diastereoselectivity, while conventional, nonumpolung methods often display high
      cis-selectivity.

PMID- 30203982
TI  - Electrically Switchable Monostable Actuatoric Polymer-Based Nanovalve Arrays with
      a Long-Term Stability.
AB  - Here we present a novel electrically switchable nanovalve array based on an
      intrinsic conductive polymer that has the capabilities to change its volume
      depending on its redox state. The polymer is created by anodic deposition of a
      sodium dodecylbenzenesulfonate (DBS)-doped polypyrrole (PPy). Optimization of the
      DBS-doped PPy layers revealed an actuatoric performance of up to 10% out of plane
      volume change. More interestingly, the electrochemical characterization revealed
      an actuatoric monostable polymer that could be used to fabricate nanovalve arrays
      that have a native opened state when no potential is applied and that can be
      closed when a reductive potential is applied. As a proof of concept, Atto488
      labeled biotin (Biotin-Atto488) was used as a model compound and defined
      nanovalve arrays with nanopores in the range of 10 nm in diameter (opened state)
      were fabricated. Afterward, we were able to successfully prove the functionality
      of our nanovalve array by monitoring the flow-through rates of the Biotin
      Atto488. More strikingly, we could demonstrate for the first time the robust and
      long-term stability of our nanovalve array without any performance loss for at
      least 72 h and retention capabilities of up to 90%. Furthermore, the demonstrated
      long-term stability was achieved under biocompatible conditions without the need
      of toxic dopant supplementation of the flow-through solution. Thus, our novel
      functional long-term stable nanovalve array offers the capabilities for practical
      applications.

PMID- 30203983
TI  - Dearomative Dienolate-Mediated Catalysis: A Remote Activation Strategy for
      Asymmetric Functionalization of Benzylic C-H Bonds of Heteroaryl Aldehydes.
AB  - A dearomative remote activation strategy for the asymmetric functionalization of
      benzylic C-H bonds of heteroaryl aldehydes under bifunctional Bronsted base
      catalysis has been developed. The in situ generated o-QDMs-type dienolate
      intermediates were efficiently and stereoselectively trapped by nitroolefins
      through an asymmetric Michael/nitro-aldol cascade reaction. Using this strategy,
      a wide variety of synthetically significant tetrahydrodibenzothiophene and
      tetrahydrodibenzofuran derivatives were synthesized in good yields with high
      enantioselectivities.

PMID- 30203984
TI  - Evaluation of miniscrew stability using an automatic embedding auxiliary skeletal
      anchorage device.
AB  - OBJECTIVE:: To clarify the in vivo effect of an automatic embedding device on
      miniscrew stability. MATERIALS AND METHODS:: 42 miniscrews were implanted into
      rabbit femurs. The miniscrews with the novel auxiliary device formed the
      auxiliary group (n = 11 at 4 weeks; n = 11 at 8 weeks) and the miniscrews without
      the auxiliary device formed the nonauxiliary control group (n = 9 at 4 weeks; n =
      11 at 8 weeks). Cortical bone thickness, distance from the cortical bone surface
      to the miniscrew head, and implantation depth of the spike were measured using
      micro-computed tomography. The mechanical retention force was evaluated by
      measuring the displacement of the miniscrew head after it was loaded
      perpendicular to its long axis. In the lateral displacement test, effects of the
      auxiliary (with vs without auxiliary), and time (4 vs 8 weeks) were assessed
      using the Brunner-Langer nonparametric analysis of longitudinal data in factorial
      experiments. RESULTS:: The mean implantation depth of the spike in the auxiliary
      group at 4 and 8 weeks was 0.28 mm (median: 0.33; SD: 0.12) and 0.37 mm (median:
      0.33; SD: 0.19), respectively. The retention force was approximately 2.0 to 2.8
      and 1.6 to 1.8 times greater in the auxiliary group than in the nonauxiliary
      group at 4 and 8 weeks, respectively. CONCLUSIONS:: The auxiliary device improved
      the mechanical retention force without the need to increase miniscrew length or
      diameter. This may enable the safe use of miniscrews in difficult areas.

PMID- 30203985
TI  - Association of exposure to Bisphenol A with obesity and cardiometabolic risk
      factors in children and adolescents.
AB  - In this study, the association of exposure to Bisphenol A (BPA) with obesity and
      cardiometabolic risk factors was investigated on 132 children and adolescents
      aged 6-18 years living in Isfahan, Iran. Potential contributors to BPA exposure
      were assessed by a questionnaire. Total BPA was detected in urine samples of all
      participants without significant difference in boys and girls. The mean body mass
      index (BMI) and waist circumference (WC) increased significantly across the BPA
      tertiles (p for trend = < 0.001). Similar trend was documented for systolic blood
      pressure (SBP) and diastolic blood pressure (DBP) as well as fasting blood sugar.
      The risk of obesity was 12.48 times higher in participants in the third tertile
      of BPA than in others (95% CI: 3.36-46.39, p < 0.001). The current study showed
      significant association between BPA exposure with obesity and some
      cardiometabolic risk factors in children and adolescents, however, further
      longitudinal studies are necessary to evaluate the clinical effects of this
      finding. Abbreviations: BMI: Body Mass Index; BPA: Bisphenol A; BSTFA: N, O
      Bistrifluoroacetamide; CDC: Centers for Disease Control and Prevention; CI:
      Circumference Interval; DBP: Diastolic Blood Pressure; DLLME: Dispersive liquid
      liquid microextraction method; FBS: Fasting Blood Glucose; HDL: high-density
      lipoprotein cholesterol were; LDL: low-density lipoprotein cholesterol; OR: Odd
      Ratio; PA: Physical Activity; SBP: Systolic Blood Pressure; TC: total
      cholesterol; TG: triglycerides; WC: Waist Circumference.

PMID- 30203986
TI  - Diagnosis of Infectious Diseases in the Lower Respiratory Tract: A
      Cytopathologist's Perspective.
AB  - CONTEXT: - Respiratory cytology continues to play an important role in the
      diagnosis of lower respiratory tract infections. Prompt, accurate diagnosis of
      causative organisms is of paramount importance, particularly in immunosuppressed
      patients. In addition, a rapidly expanding arsenal of ancillary testing is now
      available, aiding tremendously in organism identification. OBJECTIVE: - To
      provide an updated review on the cytomorphologic features of common organisms in
      lower respiratory tract infection. Relevant ancillary tests, differential
      diagnoses, and potential pitfalls of organism identification will also be
      discussed. DATA SOURCES: - Data for this review were gathered from PubMed
      searches of infectious diseases of the lower respiratory tract, especially
      related to the diagnoses. CONCLUSIONS: - The lower respiratory tract is subject
      to infection by a wide variety of infectious agents. Pathologists should be
      familiar with common organisms, including their general clinical characteristics,
      cytomorphologic features, differential diagnoses, and ancillary methods of
      detection. Above all, correlation with microbiologic and clinical information is
      necessary to make a confident diagnosis of infection.

PMID- 30203987
TI  - Verruciform and Condyloma-like Squamous Proliferations in the Anogenital Region.
AB  - CONTEXT: - Histologic distinction between condyloma acuminatum and various benign
      and malignant condyloma-like lesions in the anogenital area poses a common
      diagnostic challenge to pathologists across subspecialties. OBJECTIVE: - To
      review the overlapping and distinguishing features of condyloma acuminatum and
      its mimics, and to clarify confusing terminology and diagnostic criteria for
      problematic entities. DATA SOURCES: - A review of the literature on condyloma
      acuminatum (ordinary and giant types), verrucous carcinoma, warty/warty-basaloid
      high-grade squamous intraepithelial lesion and squamous cell carcinoma, papillary
      squamous cell carcinoma, bowenoid papulosis, verruca vulgaris, epidermolytic
      acanthoma, and verruciform xanthoma was performed. CONCLUSIONS: - Correct
      diagnosis of condyloma acuminatum and condyloma-like lesions has important
      clinical implication and entails familiarization with their clinical
      presentations and histopathologic features. Contrary to historical belief, giant
      condyloma acuminatum and verrucous carcinoma should be considered distinct
      entities based on different pathogenetic pathways. Ancillary tools available for
      identifying and genotyping human papillomavirus can aid in diagnosis when
      histopathologic findings are inconclusive. Recognition of relatively rare
      entities such as bowenoid papulosis, epidermolytic acanthoma, and verruciform
      xanthoma would avoid overdiagnosis and unnecessary, overaggressive treatment.

PMID- 30203988
TI  - A Q-Probes Study Involving Utilization of Free Prostate-Specific Antigen, Factor
      V Leiden, and Hepatitis A Serology Tests.
AB  - CONTEXT.-: Managing the utilization of laboratory tests is an important quality
      improvement activity that adds value to health care. OBJECTIVE.-: To examine
      utilization of 3 laboratory tests and identify factors that impact performance.
      DESIGN.-: Test utilization performance was evaluated by determining the frequency
      with which appropriate preconditions for testing were met. This included 30
      testing episodes each involving (1) free prostate-specific antigen (PSA) when
      total PSA was within an appropriate interpretable range, (2) total anti-hepatitis
      A virus antibody when previous anti-hepatitis A virus antibody results were
      either negative or not done, and (3) factor V Leiden mutation when a previous
      result was not already available. Participants also provided information
      regarding some of their utilization policies and procedures for these 3 tests.
      RESULTS.-: The overall frequency with which testing criteria were met was 20.6%
      (163 of 790), 91.5% (649 of 709), and 95.2% (799 of 839) for free PSA, anti
      hepatitis A virus antibody, and factor V Leiden, respectively. Utilization review
      was infrequent and done by 20.7% (6 of 29) of participants for factor V Leiden,
      3.6% (1 of 28) for anti-hepatitis A virus antibody, and 3.6% (1 of 28) for free
      PSA. No practice or demographic characteristics were significantly associated
      with utilization performance for any test. CONCLUSIONS.-: Utilization review was
      infrequent for the 3 tests examined. Variable amounts of unnecessary testing were
      observed for all tests, most frequently for free PSA, for which reporting results
      carried the added risk of diagnostic error from misinterpretation of results.

PMID- 30203990
TI  - Metrics.

PMID- 30203989
TI  - The effect of dexmedetomidine on haemodynamics during intracranial procedures: a
      meta-analysis.
AB  - OBJECTIVES: Our aim of this study is to compare the effect of Dexmedetomidine
      versus placebo for patients with cerebral protection during intracranial
      procedures. METHODS: Rev.Man 5.1 and Stata 11.0 software is used for this study
      to make analysis, and use a fixed-effects model (the Mantel-Haenszel method) or a
      random-effects model (the DerSimonian and Laird method) to merge or aggregate the
      weighted mean difference (WMD) or risk ratio (RR) and its 95% confidence
      intervals (CI) of included studies. RESULTS: Nine studies involving 404 patients
      with cerebral protection during intracranial procedures (experimental group: 202;
      control group: 202) were performed in this study. Significant differences of MAP
      > 100 mmHg(RR = 0.45, 95%CI = 0.29 to 0.69, P < 0.05), MAP< 60 mmHg (RR = 0.66,
      95%CI = 0.43 to 1.00, P = 0.05), MAP when extubation (WMD = -12.57, 95%CI = 
      16.31 to -8.83, P < 0.05) and heart rate when extubation (WMD = -22.79, 95%CI = 
      30.57 to -15.01, P < 0.05) were observed between the two groups. There are no
      significant differences were found in HR > 100 bpm (RR = 0.52, 95%CI = 0.22 to
      1.19, P > 0.05) and HR< 50 bpm (RR = 0.86, 95%CI = 0.31 to 2.38, P > 0.05)
      between the two groups. CONCLUSIONS: Our results suggested that the efficacy of
      Dexmedetomidine for patients with cerebral protection during intracranial
      procedures is better than placebo treatment.

PMID- 30203991
TI  - Moving NIEHS Forward for the Next Five Years.

PMID- 30203992
TI  - Fine and Coarse Particulate Matter Exposures and Associations with Acute Cardiac
      Events among Participants in a Telemedicine Service: A Case-Crossover Study.
AB  - BACKGROUND: Subclinical cardiovascular changes have been associated with ambient
      particulate matter (PM) exposures within hours. Although the U.S. Environmental
      Protection Agency continues to look for additional evidence of effects associated
      with sub-daily PM exposure, this information is still limited because most
      studies of clinical events have lacked data on the onset time of symptoms to
      assess rapid increased risk. OBJECTIVE: Our objective was to investigate
      associations between sub-daily exposures to PM and acute cardiac events using
      telemedicine data. METHODS: We conducted a case-crossover study among
      telemedicine participants [Formula: see text] of age who called a service center
      for cardiac-related symptoms and were transferred to a hospital in Tel Aviv and
      Haifa, Israel (2002-2013). Ambient [Formula: see text] and [Formula: see text]
      measured by monitors located in each city during the hours before the patient
      called with symptoms were compared with matched control periods. We investigated
      the sensitivity of these associations to more accurate symptom onset time and
      greater certainty of diagnosis. RESULTS: We captured 12,661 calls from 7,617
      subscribers experiencing ischemic (19%), arrhythmic (31%), or nonspecific (49%)
      cardiac events. PM concentrations were associated with small increases in the
      odds of cardiac events. For example, odds ratios for any cardiac event in
      association with a [Formula: see text] increase in 6-h and 24-h average [Formula:
      see text] were 1.008 [95% confidence interval (CI): 0.998, 1.018] and 1.006 (95%
      CI: 0.995, 1.018), respectively, and for [Formula: see text] were 1.003 (95% CI:
      1.001, 1.006) and 1.003 (95% CI: 1.000, 1.007), respectively. Associations were
      stronger when using exposures matched to the call time rather than calendar date
      and for events with higher certainty of the diagnosis. CONCLUSIONS: Our analysis
      of telemedicine data suggests that risks of cardiac events in telemedicine
      participants [Formula: see text] of age may increase within hours of PM
      exposures. https://doi.org/10.1289/EHP2596.

PMID- 30203993
TI  - Association of Prenatal Urinary Concentrations of Phthalates and Bisphenol A and
      Pubertal Timing in Boys and Girls.
AB  - BACKGROUND: Animal studies suggest that phthalates and bisphenol A (BPA),
      endocrine-disrupting chemicals found in many consumer products, may impact the
      timing of puberty. OBJECTIVES: We aimed to determine the association of prenatal
      exposure to high-molecular-weight phthalates and BPA with pubertal timing in boys
      and girls participating in the Center for the Health Assessment of Mothers and
      Children of Salinas (CHAMACOS) longitudinal cohort study. METHODS: We quantified
      urinary concentrations of eight phthalate metabolites and BPA at two time points
      during pregnancy among participating mothers ([Formula: see text]) and conducted
      clinical Tanner staging of puberty on their children every 9 months between 9 and
      13 y of age. We conducted accelerated failure time models and examined the role
      of child overweight/obese status in this association. RESULTS: The sum of urinary
      metabolites of di(2-ethylhexyl) phthalate [Formula: see text], monobenzyl
      phthalate (MBzP), and BPA were associated with later onset of at least one of the
      three outcomes assessed in girls (thelarche, pubarche, or menarche) and with
      earlier onset of at least one of the two outcomes assessed in boys (gondarche and
      pubarche). We found that monocarboxynonyl phthalate, monocarboxyoctyl phthalate,
      mono(3-carboxypropyl) phthalate, and BPA were associated with later pubarche and
      menarche mostly among normal-weight girls but not overweight/obese girls. MBzP
      was associated with later thelarche in all girls, and [Formula: see text] was
      associated with later thelarche and menarche in all girls. BPA and all phthalate
      biomarkers were associated with earlier gonadarche and pubarche in all boys as
      well as in overweight/obese boys when stratified by weight. Among normal-weight
      boys, associations with BPA were also inverse, whereas associations with
      phthalate metabolites were close to the null or positive. CONCLUSIONS: Several
      high-molecular-weight phthalates and BPA were associated with later puberty in
      girls and earlier puberty in boys included in the CHAMACOS cohort study.
      Childhood overweight/obesity may modify these associations.
      https://doi.org/10.1289/EHP3424.

PMID- 30203995
TI  - Mass spectrometry imaging: How will it affect clinical research in the future?
AB  - INTRODUCTION: Mass spectrometry imaging (MSI) is a label free, multiplex imaging
      technology able to simultaneously record the distributions of 100's to 1000's of
      species, and which may be configured to study metabolites, lipids, glycans,
      peptides, and proteins simply by changing the tissue preparation protocol. Areas
      covered: The capability of MSI to complement established histopathological
      practice through the identification of biomarkers for differential diagnosis,
      patient prognosis, and response to therapy; the capability of MSI to annotate
      tissues on the basis of each pixel's mass spectral signature; the development of
      reproducible MSI through multicenter studies. Expert commentary: We discuss how
      MSI can be combined with microsampling/microdissection technologies in order to
      investigate, with more depth of coverage, the molecular changes uncovered by MSI.

PMID- 30203996
TI  - Gemcitabine induced cytotoxicity, DNA damage and hepatic injury in laboratory
      mice.
AB  - The present study was conducted to demonstrate cytotoxicity, apoptosis and
      hepatic damage induced by gemcitabine in laboratory mice. Animals were treated
      with a single dose of gemcitabine (415 mg/kg body wt), equivalent to a human
      therapeutic dose, and sacrificed after 1, 2 and 3 weeks. A significant decrease
      in mean body weight and absolute liver weight was registered. The levels of
      alkaline phosphatase (ALP), aspartate aminotransferase (AST) and alanine
      aminotransferase (ALT) were increased as a result of this induced stress. Various
      structural changes were observed in the liver tissue of treated mice, as evident
      in the histological sections. Specifically, gemcitabine exposure was able to
      induce apoptosis in liver cells, and the incidence of TUNEL positive liver cells
      was increased compared to the control group. DNA fragmentation appeared on
      agarose gel and flow cytometry analysis confirmed the induction of apoptosis.
      These findings in gemcitabine-treated animal tissues suggest that inhibition or
      disruption of cells' DNA synthesis may be the mechanism by which this drug
      induces toxicity in the animal body.

PMID- 30203997
TI  - Recent advances in the molecular diagnosis of mucormycosis.
AB  - INTRODUCTION: Fungal infection burden related to Mucorales has been on the rise
      with significant associated morbidity and mortality. The major obstacle in the
      management has been lack of a non-invasive rapid and a reliable diagnostic test.
      Developing a culture-independent biomarker for the early diagnosis of
      mucormycosis is a major unmet need in modern mycology. Several approaches have
      been developed, such as immunohistochemistry (IHC) that can confirm the
      histopathologic diagnosis of the invasive mold infection, polymerase chain
      reaction (PCR) on formalin-fixed paraffin-embedded (FFPE) or fresh tissue, body
      fluids such as bronchoalveolar fluid (BAL), and detection directly from
      serum/blood. Serologic tests, matrix assisted laser desorption/ionization time-of
      flight mass spectrometry (MALDI-TOF/MS), metabolomics and metagenomic shotgun
      sequencing are other evolving technologies. Area covered: In this review paper,
      we report the current status of the molecular diagnostics in the diagnosis of
      mucormycosis: serologic tests, IHC, PCR, protein-based with MALDI-TOF,
      metabolomics and metagenomic sequencing. Expert commentary: This review will
      conclude with an expert commentary on the potential uses/challenges of the
      currently available tests and the future of molecular diagnostics for
      mucormycosis.

PMID- 30203998
TI  - How can the World Health Organization's International Classification of Diseases
      (ICD)-11 change the clinical management of anaphylaxis?

PMID- 30203999
TI  - Total knee arthroplasty in the face of a previous tuberculosis infection of the
      knee: what do we know in 2018?
AB  - INTRODUCTION: TB of the knee is often associated with marked morbidity because of
      its late and non-specific presentation. The use of TKA (total knee arthroplasty)
      in the face of a previous tuberculous knee infection has been criticized with
      multiple controversies. Therefore, the purpose of this review is to assess: (1)
      clinical outcomes, (2) radiographic outcomes, and (3) complications of TKA in the
      face of a previous healed TB infection. Our analysis has demonstrated that
      previous TB infection of the knee joint does not preclude TKA if indicated and
      suggests placing patients who have ESR or CRP results out of normal range on pre
      operative anti-TB prophylactic antibiotic for a minimum of 2 weeks. In case of
      local recurrence following TKA, antibiotic therapy alone can be an effective
      treatment option. Areas covered: We examined reported outcomes of performing TKA
      in patients with previous TB infection of the knee. Different strategies
      recommended by different authors to maximize the success of TKA in this situation
      are also discussed. Expert commentary: TKA has been proven to be effective in
      patients who are status post tuberculous arthritis when thoughtful patient
      selection and peri-operative planning is conducted. Tuberculosis continues to
      have a rising incidence and increasing spread of multi-drug resistant strains.

PMID- 30204001
TI  - Evaluation of the cytotoxic and genotoxic effects of mycotoxin fusaric acid.
AB  - Fusaric acid (FA) is produced by several Fusarium species and is commonly found
      in grains. This investigation was performed to evaluate the cytotoxic and
      genotoxic effects of FA either in human cervix carcinoma (HeLa) cell line using 3
      (4,5-dimethylthiazolyl-2)-2,5 diphenyltetrazolium bromide (MTT) assay and in
      human lymphocytes using chromosome aberrations (CAs), sister chromatid exchanges
      (SCEs), micronuclei (MN) as well as comet assay in vitro. The cells were treated
      with 0.78, 1.56, 3.125, 6.25, 12.50, 25, 50, 100, 200, and 400 ug/mL
      concentrations of FA. It has potent cytotoxic effect on HeLa cell line measured
      by MTT assay especially at higher concentrations (200, 400 ug/mL). The half of
      inhibitory concentration (IC50) evidenced by FA in the HeLa cells was 200 MUg/mL
      at 24 h and between 200 and 400 MUg/mL at 48 h. It was also observed that FA
      produced a significant decrease in mitotic index (MI) at 12.50 ug/mL compared to
      solvent control. Furthermore, it indicated a cytotoxic effect at the
      concentrations ranging from 25 to 400 MUg/mL in human lymphocytes. The results of
      this research point out that being exposed to FA at high concentrations show
      cytotoxicity. Besides FA induced comet tail intensity at 3.125, 6.25, and 12.50
      ug/mL concentrations in isolated human lymphocytes. On the other hand, no
      genotoxic effects were seen in human lymphocytes in vitro using CA, SCE and MN
      assays.

PMID- 30204000
TI  - Thirty-five alternatives to positive airway pressure therapy for obstructive
      sleep apnea: an overview of meta-analyses.
AB  - INTRODUCTION: Positive airway pressure (PAP) devices are generally considered to
      be the first-line treatment of choice for most adults with obstructive sleep
      apnea (OSA). However, there are several alternatives. It is important for
      patients and their sleep providers to be aware of the most up-to-date information
      regarding the current international literature. Areas covered: The objective is
      to provide an overview of the meta-analyses evaluating non-PAP treatments for
      OSA. Four authors searched four databases, including PubMed/MEDLINE through 30
      November 2017, for meta-analyses evaluating non-PAP therapies as treatment for
      OSA. Thirty-five non-PAP treatments were identified and were categorized based on
      the following anatomical subsites: (1) nose, (2) palate and oropharynx, (3)
      tongue, (4) skeletal surgery and jaw repositioning, and (5) other surgical and
      medical interventions. Treatments identified included surgeries, drugs, behavior
      modifications, nonsurgical weight loss, medical devices, body positioning, and
      oxygen treatment. Expert commentary: The 35 treatments described vary in their
      effectiveness in treating OSA in adults. In general, isolated nasal treatments
      are the least effective, whereas treatments that bypass the upper airway,
      significantly open the upper airway, and/or address multiple levels of the upper
      airway are more effective in improving apnea-hypopnea index and lowest oxygen
      saturation.

PMID- 30204003
TI  - Dissolving microneedles for intradermal vaccination: manufacture, formulation,
      and stakeholder considerations.

PMID- 30204002
TI  - Effect of Carnauba Wax-Based Coating Containing Glycerol Monolaurate on Decay and
      Quality of Sweet Potato Roots during Storage.
AB  - Because of high water loss and rot observed in postharvest sweet potato ( Ipomoea
      batatas (L.) Lam.) roots, a carnauba wax (CW)-based nanoemulsion without or with
      glycerol monolaurate (CW-GML) was developed by a high-energy emulsification
      approach. The effects of the two coatings on decay, respiration rate, weight
      loss, surface color, total soluble sugar, and starch content as well as the
      sensory quality of sweet potato roots were investigated during storage at 20
      degrees C for 50 days. Compared with the control treatment (water) and CW coating
      alone, CW-GML coating exhibited higher emulsion stability and antifungal
      activity, and treatment resulted in a uniform and continuous coating on roots.
      The CW-GML and CW coatings both effectively reduced root weight loss and
      respiration rate and inhibited decay incidence compared with control roots during
      storage. The CW-GML coating showed markedly stronger inhibition of root rot than
      the CW coating. Both the CW-GML and CW coatings promoted an increase in root
      sweetness but did not negatively impact perceived flavor. The overall results
      demonstrate that the CW-GML coating holds great promise as an effective
      postharvest technology to preserve food quality and extend shelf life of sweet
      potato roots.

PMID- 30204004
TI  - Ultrasound-guided laser ablation for local control of neck recurrences of
      medullary thyroid cancer. A feasibility study.
AB  - BACKGROUND: Surgery is the standard treatment for cervical metastases of
      medullary thyroid cancer (MTC) diagnosed after initial surgical treatment.
      Repeated neck dissections, however, carry an elevated risk of complications, have
      an adverse impact on the quality of life, and sometimes do not achieve cure of
      the disease Clinical case: In a patient who had undergone two cervical neck
      dissections complicated by accessory nerve injury, an US-guided laser ablation
      (LA) of a lymph node metastasis of MTC was performed. LA was performed with two
      treatments during a five month period. The procedure was carried out with one
      optical fiber and an energy delivery of 3300 and 360 Joules. Treatments were well
      tolerated and resulted in complete structural and biochemical cure during a 12
      month follow-up. No major complication was registered. CONCLUSIONS: LA is a
      promising tool for the management of relapsing cervical metastases that are
      localized in non- critical areas and are characterized by low progression rate.
      Advantages of LA are the outpatient setting, the absence of general anesthesia,
      the tolerability and the safety of the procedure. Thus, LA may be considered as
      an alternative approach to surgery or active surveillance for the management of
      local recurrences of MTC in selected patients.

PMID- 30204005
TI  - Liver cancer-associated changes to the proteome: what deserves clinical focus?
AB  - INTRODUCTION: Hepatocellular carcinoma (HCC) is recognized as the fifth most
      common neoplasm and currently represents the second leading form of cancer
      related death worldwide. Despite great progress has been done in the
      understanding of its pathogenesis, HCC represents a heavy societal and economic
      burden as most patients are still diagnosed at advanced stages and the 5-year
      survival rate remain below 20%. Early detection and revolutionary therapies that
      rely on the discovery of new molecular biomarkers and therapeutic targets are
      therefore urgently needed to develop precision medicine strategies for a more
      efficient management of patients. Areas covered: This review intends to
      comprehensively analyse the proteomics-based research conducted in the last few
      years to address some of the principal still open riddles in HCC biology, based
      on the identification of molecular drivers of tumor progression and metastasis.
      Expert commentary: The technical advances in mass spectrometry experienced in the
      last decade have significantly improved the analytical capacity of proteome wide
      studies. Large-scale protein and protein variant (post-translational
      modifications) identification and quantification have allowed detailed
      dissections of molecular mechanisms underlying HCC progression and are already
      paving the way for the identification of clinically relevant proteins and the
      development of their use on patient care.

PMID- 30204006
TI  - Systematic quality assurance of the BSD2000-3D MR-compatible hyperthermia
      applicator performance using MR temperature imaging.
AB  - BACKGROUND: Radiofrequency (RF) mild hyperthermia (40  degrees C-44  degrees C
      for 60 minutes) is an effective adjuvant treatment for several types of cancer.
      To ensure treatment efficacy, quality assurance (QA) is necessary. This study
      presents the first systematic 3D characterisation of the heating performance of
      the commonly used Pyrexar BSD2000-3D MR-compatible hyperthermia applicator using
      magnetic resonance temperature imaging (MRTI). METHODS: A reproducibly positioned
      phantom was heated with a power of 1000 watts during the 12.4 min needed to
      measure eight temperature distributions using MRTI. The target heating location
      was systematically varied between experiments. We analysed focus shape
      characteristics, steering accuracy, focus deformation due to steering, presence
      of off-target heating and reproducibility. RESULTS: The mean maximum temperature
      increase was 5.9 +/- 0.4  degrees C. The mean full width half maximum (FWHM) was
      14.4 +/- 0.5 cm in the XY plane and 24.5 +/- 0.8 cm in Z-direction. The mean
      steering error was 0.4 +/- 0.2 cm. The focus shape slightly varied between
      experiments, depending on steering distance in Y-direction. Off-target heating
      was not detected. Reproducibility of the focus amplitude and shape was determined
      by comparing the mean deviation from the mean temperature in the central slice
      was 0.3 +/- 0.2  degrees C. CONCLUSION: The Pyrexar BSD2000-3D MR-compatible
      applicator provides robust and reproducible heating. The upper boundary of the
      95% confidence interval of the spatial steering accuracy is 0.9 cm, i.e.
      sufficient to fulfil the criterion of <=0.2  degrees C temperature variation due
      to positioning errors as defined by Canters et al.

PMID- 30204007
TI  - Ultrasound and cone beam CT fusion for liver ablation: technical note.
AB  - PURPOSE: To assess the feasibility of fusion imaging between intraprocedural
      ultrasound (US) and contrast-enhanced cone-beam CT (CBCT) for small (< 2 cm)
      hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Six patients (five males,
      one female, age range 58-80, mean 69 years), with small (mean diameter 16.8 mm)
      HCC poorly visible at US underwent percutaneous microwave ablation under US/CBCT
      fusion guidance. During general anesthesia with apnea control, a contrast-
      enhanced CBCT was acquired with an active tracker. Subsequently, real time US
      images were fused with CBCT images, and treatment performed under fusion imaging
      guidance. Feasibility of fusion imaging and percutaneous ablation were assessed,
      correct targeting (distance from center of tumor and center of ablation area <5
      mm) and one-month primary technical efficacy were evaluated. Major and minor
      complications as well as overall procedural time were recorded. RESULTS: US/CBCT
      fusion was feasible in all cases, allowing for completion of the treatment as
      previously planned (technical success 100%). Correct targeting was achieved in
      4/6 cases (66%), while in two cases, center of tumor and center of ablated area
      were respectively 7 and 8 mm distant. At 1 month CT scan, all tumors were
      completely ablated (primary technical efficacy 100%). No major or minor
      complications occurred. Mean overall procedure time was 127 min. CONCLUSIONS:
      US/CBCT fusion is a feasible technique for liver ablation, and might represent a
      useful tool to increase the correct targeting of poorly US-visible HCC nodules in
      the angio suite.

PMID- 30204008
TI  - Estimation of the temperature field in laser-induced hyperthermia experiments
      with a phantom.
AB  - BACKGROUND: One of the challenges faced during the hyperthermia treatment of
      cancer is to monitor the temperature distribution in the region of interest. The
      main objective of this work was to accurately estimate the transient temperature
      distribution in the heated region, by using a stochastic heat transfer model and
      temperature measurements. METHODS: Experiments involved the laser heating of a
      cylindrical phantom, partially loaded with iron oxide nanoparticles. The
      nanoparticles were manufactured and characterized in this work. The solution of
      the state estimation problem was obtained with an algorithm of the Particle
      Filter method, which allowed for simultaneous estimation of state variables and
      model parameters. Measurements of one single sensor were used for the estimation
      procedure, which is highly desirable for practical applications in order to avoid
      patient discomfort. RESULTS: Despite the large uncertainties assumed for the
      model parameters and for the coupled radiation-conduction model, discrepancies
      between estimated temperatures and internal measurements were smaller than 0.7 
      degrees C. In addition, the estimated fluence rate distribution was physically
      meaningful. Maximum discrepancies between the prior means and the estimated means
      were of 2% for thermal conductivity and heat transfer coefficient, 4% for the
      volumetric heat capacity and 3% for the irradiance. CONCLUSIONS: This article
      demonstrated that the Particle Filter method can be used to accurately predict
      the temperatures in regions where measurements are not available. The present
      technique has potential applications in hyperthermia treatments as an observer
      for active control strategies, as well as to plan personalized heating protocols.

PMID- 30204009
TI  - Acute Necrotizing Pancreatitis in a Yellow-naped Amazon Parrot ( Amazona
      auropalliata).
AB  - A 25-year-old female yellow-naped Amazon parrot ( Amazona auropalliata) was
      presented for an acute onset of lethargy, ptyalism, and regurgitation. Results of
      hematologic testing and plasma biochemical analysis revealed severe leukopenia
      and heteropenia with toxic heterophils and marked hyperamylasemia and
      hypoproteinemia, consistent with gastrointestinal dysfunction. Survey radiograph
      findings were suggestive of coelomic effusion. Results of a contrast-enhanced
      computed tomography (CT) scan revealed a tubular, irregularly marginated
      structure along the medial aspect of the duodenum, consistent with an inflamed
      pancreas. The bird died soon after CT imaging, and acute necrotizing pancreatitis
      and pancreatic coagulative necrosis were observed at necropsy. This report
      describes the use of a less-invasive modality such as CT to aid in the antemortem
      diagnosis of acute pancreatitis in a psittacine bird. Pancreatitis should be
      considered a differential diagnosis in birds with gastrointestinal signs and
      coelomic effusion visualized on radiography, and the observation of an enlarged
      inflamed pancreas in the absence of a defined pancreatic mass on CT.

PMID- 30204011
TI  - Bilateral Malignant Seminoma With Ventricular Metastasis in a Bald Eagle (
      Haliaeetus leucocephalus).
AB  - A 30-year-old bald eagle ( Haliaeetus leucocephalus) was presented with a history
      of hyporexia and lethargy. Results of initial hematologic testing, biochemical
      analysis, and fecal examination were unremarkable, and clinical signs did not
      resolve with supportive care and management changes. Results of echocardiography,
      based on auscultation of a murmur, and coelomic endoscopy, based on the presence
      of a soft tissue opacity on radiographs, as well as an aspergillosis panel were
      largely unsuccessful in determining a definitive diagnosis. Euthanasia was
      performed after the eagle did not recover from anesthesia after endoscopy.
      Necropsy results demonstrated bilateral testicular seminomas with metastases to
      the ventriculus. This case demonstrates an abnormal metastasis of a common
      reproductive tumor in an avian species.

PMID- 30204012
TI  - Avian Veterinarians: Not Just Clinical Practitioners.

PMID- 30204014
TI  - Coming Meetings.

PMID- 30204013
TI  - True Coelomic Hernia and Herniorrhaphy in a Yellow-crowned Amazon Parrot (
      Amazona ochrocephala).
AB  - An 8-year-old male yellow crowned Amazon parrot ( Amazona ochrocephala) was
      presented for an 8-month history of intermittent regurgitation, anorexia, and
      lethargy along with a 3-week history of a soft tissue mass cranial to the vent.
      Examination revealed a small soft tissue mass, approximately 2 cm in diameter,
      within the body wall of the coelomic cavity with no discoloration of the
      surrounding tissue. Full body computed tomography (CT) revealed a defect in the
      body wall on the ventral coelom from the right paramedian location extending to
      the right side, which contained intestines. Surgical exploration allowed for
      reduction of the coelomic hernia, which was encased in fibrous tissue and
      contained a well-vascularized and motile loop of bowel. The hernia sac was
      excised before closing the body wall in a simple interrupted pattern. Three
      months postoperatively, the bird was reported to be doing well at home with no
      further episodes of regurgitation or anorexia.

PMID- 30204015
TI  - Lead Levels in the Eggs of a Chicken With Lead Toxicosis.
AB  - A 1.5-year-old Polish hen was presented with a history of watery droppings and
      poor vent tone. Results of diagnostic tests revealed blood lead at levels
      considered to be toxic. Chelation therapy was started with calcium
      ethylenediaminetetraacetate. The hen was laying eggs before, during, and after
      chelation therapy. Eggs were tested for the presence of lead by combining yolk
      and albumen together. Before chelation therapy, the level of lead in the egg
      tested was 14 MUg. Two days after the end of chelation therapy, results of a
      second blood lead test revealed a drop to nontoxic levels. No lead was detected
      in the combined yolks and albumen of eggs collected 7-11 days after the end of
      chelation therapy. Four weeks after the end of chelation therapy, no lead was
      identified in the shells of tested eggs.

PMID- 30204018
TI  - Successful Management of Open, Contaminated Metacarpal Fractures in an Adult
      Snowy Owl ( Bubo scandiacus) With a Minimal Type II External Skeletal Fixator.
AB  - An adult, male snowy owl ( Bubo scandiacus) was found down and unable to fly in
      western New York State. Physical examination and radiographs revealed a subacute,
      open wound and fractured major and minor metacarpals of the right wing. A minimal
      type II external skeletal fixator (ESF) device was placed on the right major
      metacarpal bone and the open wound was allowed to granulate and close. After
      evidence of bone union, the ESF device was removed. The owl performed auto
      physiotherapy throughout the process and was released with sustained flight 2
      months postoperatively. It was recaptured 7 weeks later and underwent further
      rehabilitation to allow successful release 11 months after surgical
      stabilization. To our knowledge, this is the first case report describing use of
      a type II ESF device on the metacarpus of a bird.

PMID- 30204017
TI  - Preliminary Findings of Structure and Expression of Opioid Receptor Genes in a
      Peregrine Falcon ( Falco peregrinus), a Snowy Owl ( Bubo scandiacus), and a Blue
      fronted Amazon Parrot ( Amazona aestiva).
AB  - To further knowledge of the physiology of opioid receptors in birds, the
      structure and expression of the MU-, delta-, and kappa-opioid receptor genes were
      studied in a peregrine falcon ( Falco peregrinus), a snowy owl ( Bubo
      scandiacus), and a blue-fronted Amazon parrot ( Amazona aestiva). Tissue samples
      were obtained from birds that had been euthanatized for poor release prognosis or
      medical reasons. Samples were taken from the brain (telencephalon, thalamus,
      pituitary gland, cerebellum, pons, medulla oblongata, mesencephalon), the spinal
      cord and dorsal root ganglions, and plantar foot skin. Messenger RNA was
      recovered, and reverse transcription polymerase chain reaction (RT-PCR) was
      performed to generate complementary DNA (cDNA) sequences. Gene structures were
      documented by directly comparing cDNA sequences with recently published genomic
      sequences for the peregrine falcon and the blue-fronted Amazon parrot or by
      comparisons with genomic sequences of related species for the snowy owl.
      Structurally, the avian MU-opioid receptor messenger RNA (mRNA) species were
      complex, displaying differential splicing, alternative stop codons, and multiple
      polyadenylation signals. In comparison, the structure of the avian kappa-receptor
      mRNA was relatively simple. In contrast to what is seen in humans, the avian
      delta-receptor mRNA structure was found to be complex, demonstrating novel 3
      prime coding and noncoding exons not identified in mammals. The role of the delta
      opioid receptor merits further investigation in avian species.

PMID- 30204019
TI  - Retrospective Evaluation of Tibiotarsal Fractures Treated With Tape Splints in
      Birds: 86 Cases (2006-2015).
AB  - Tibiotarsal fractures are a common presentation in small bird species and
      anecdotally have been reported to carry a good prognosis with proper treatment,
      such as external coaptation. For this retrospective study, the medical records of
      5 institutions were reviewed for tibiotarsal fractures diagnosed in companion
      birds weighing less than 200 g. A total of 86 cases met the inclusion criteria.
      Cockatiels ( Nymphicus hollandicus) (24/86) and budgerigars ( Melopsittacus
      undulatus) (19/86) were the most frequently represented species. Median body
      weight of the birds included was 72 g (range, 16-182 g). Mid-diaphyseal (46/86)
      and closed (73/86) fractures with intact, deep pain sensation in the affected
      limb (69/76) were most frequent. A tape splint alone (79/86) or a tape splint in
      addition to an intramedullary pin (7/86) were applied in all cases. Median time
      to fracture stabilization based on palpation was 19 days (range, 7-49 days). In
      most cases (61/86), the initial splint applied was maintained until fracture
      healing was complete. A successful outcome was documented in 92% (79/86) of
      birds. Fractures caused by a dog or cat attack, birds presenting without deep
      pain sensation in the affected limb, and cases where the splint was removed
      before 14 days after fixation were associated with a significantly increased risk
      of complications, resulting in an unsuccessful outcome. The findings of this
      study indicated that a tape splint is an appropriate means for treatment of
      tibiotarsal fractures in birds weighing less than 200 g.

PMID- 30204020
TI  - Subclinical Lead Exposure Among Backyard Chicken Flocks in Massachusetts.
AB  - Ownership of backyard chickens (BYCs) is increasing in urban areas, and BYCs
      often have access to soil around the home. Exposure to lead-contaminated soil is
      a known health risk for people; however, the degree to which BYCs are exposed is
      unknown. We employed a cross-sectional convenience sample to assess blood lead
      levels (BLLs) in 57 BYCs from 30 flocks in a region with established
      environmental lead contamination. Over two-thirds (70.2%) had detectable levels
      of lead in their blood, which averaged 12.5 MUg/dL (range: <3.3 MUg/dL to >=65.0
      MUg/dL). No chickens demonstrated clinical evidence of lead toxicosis. Almost all
      owners (96.2%) reported that their chickens had free access to soil, and almost
      three-quarters (69.2%) of the participants reported giving their chickens
      unrestricted access to the property. Our findings demonstrate that subclinical
      but elevated BLLs are common in BYCs that live in an environment where lead
      contamination may be present. Our data support the inclusion of blood lead
      testing in the routine veterinary care of BYCs, especially in areas where
      historic use of leaded paint and environmental lead contamination are reported.

PMID- 30204022
TI  - What Is Your Diagnosis?

PMID- 30204021
TI  - Retrospective Evaluation of Clinical Signs and Gross Pathologic Findings in Birds
      Infected With Mycobacterium genavense.
AB  - Mycobacterium genavense is regarded as the primary cause of mycobacteriosis in
      passerine and psittacine birds kept in captivity. Mycobacterium genavense is a
      potential zoonotic pathogen; therefore, early antemortem detection in birds is
      needed. In humans, infections with M genavense are found predominantly in
      immunocompromised people. To investigate clinical signs and pathologic lesions
      and to determine the prevalence of coinfections in birds infected with M
      genavense, we reviewed records of 83 birds in which DNA from M genavense had been
      detected via real-time polymerase chain reaction. To evaluate clinical signs in
      birds presented as patients, results of standardized examinations of 60 birds and
      radiographic results from 37 birds were investigated. Necropsy results of 82 of
      the 83 birds were evaluated, including results of additional parasitologic,
      bacteriologic, and virologic examinations. Birds included in the study comprised
      15 species in the orders Passeriformes, Psittaciformes, Coliiformes,
      Columbiformes, Coraciiformes, and Ciconiiformes. A wide range of clinical
      manifestations were documented, including neurologic disorders, ocular
      manifestations, and gastrointestinal signs. Of the 60 birds examined clinically,
      15% showed no clinical signs. Coinfections with a wide range of pathogens were
      detected in 52% (43 of 83) of the tested birds. Coinfections included
      Macrorhabdus ornithogaster, circovirus, polyomavirus, avian bornavirus,
      adenovirus, Mycobacterium avium ssp. avium/ silvaticum, Mycoplasma species,
      Salmonella species, Escherichia coli, Aspergillus species, and various parasites.
      The high number of coinfections may reflect an impaired immune status in the
      birds examined. These results also suggest a broad host range for M genavense,
      and the existence of various clinical signs that may be strongly associated with
      coinfections with other pathogens.

PMID- 30204023
TI  - Mixed Thymoma in an American Robin ( Turdus migratorius).
AB  - A mixed thymoma was diagnosed in a 15-year-old female American robin ( Turdus
      migratorius) that exhibited poor body condition, dysphagia, hyporexia, and
      depression. A 1.5-cm subcutaneous nodule was present in the cranio-ventral
      cervical region, which had been noticed by the owner 15 days before presentation.
      On cytologic evaluation of a fine-needle aspirate, well-differentiated
      lymphocytes were observed. Surgical excision was elected; however, the mass was
      firmly attached to the esophagus and the jugular vein, and the attempt at
      excision resulted in fatal hemorrhage. On histologic examination of the mass,
      small, well-differentiated lymphocytes were observed mixed with neoplastic
      reticular cells and Hassall's corpuscles. On immunohistochemical analysis, the
      cytoplasm of 80% of the reticular cells showed abundant detectable brown antigen
      binding with pancytokeratin staining, and most lymphoid cells showed detectable
      antigen in the cytoplasm by using CD3 antibodies. The cytologic, histopathologic,
      and immunohistochemical features of the neoplasm in this robin were consistent
      with a mixed thymoma.

PMID- 30204024
TI  - High intensity focused ultrasound (HIFU) for the treatment of symptomatic breast
      fibroadenoma.
AB  - PURPOSE: The aim of the study was to evaluate the efficacy of high intensity
      focused ultrasound (HIFU) in the treatment of symptomatic breast fibroadenomas
      (FA) after 6 and 12 months. MATERIALS AND METHODS: Between December 2013 and
      November 2014, 27 patients with histologically confirmed FA received one
      application of HIFU under local anesthesia (NCT02011919). Follow-up visits
      occurred after 6 and 12 months measuring the FA volume and clinical symptoms. A
      volume reduction of more than 65% was defined as success. Core needle biopsy
      (CNB) was offered after 12 months if indistinct residuals were visible on
      ultrasound (US). RESULTS: A successful reduction in FA volume after 12 months was
      achieved in 24/27 patients (89%). At baseline 16 patients (59%) had pain, which
      was resolved in 63% (10/16). All patients were satisfied with the cosmetic
      related outcome. Twenty-four patients (89%) would repeat the procedure. After 12
      months 21 patients with sonographically indistinct residuals underwent a CNB.
      There were no vital cells in 86%. Three cases showed vital cells of FA.
      Retrospectively possible reasons in these three cases were an insufficient
      treatment due to bad visibility and insufficient fixation of the FA during HIFU
      and/or a too short follow-up time. CONCLUSION: US-guided HIFU is an effective
      procedure and a minimally invasive alternative for the treatment of breast FA.

PMID- 30204025
TI  - Beyond p-values: A phase II dual-criterion design with statistical significance
      and clinical relevance.
AB  - Background Well-designed phase II trials must have acceptable error rates
      relative to a pre-specified success criterion, usually a statistically
      significant p-value. Such standard designs may not always suffice from a clinical
      perspective because clinical relevance may call for more. For example, proof-of
      concept in phase II often requires not only statistical significance but also a
      sufficiently large effect estimate. Purpose We propose dual-criterion designs to
      complement statistical significance with clinical relevance, discuss their
      methodology, and illustrate their implementation in phase II. Methods Clinical
      relevance requires the effect estimate to pass a clinically motivated threshold
      (the decision value (DV)). In contrast to standard designs, the required effect
      estimate is an explicit design input, whereas study power is implicit. The sample
      size for a dual-criterion design needs careful considerations of the study's
      operating characteristics (type I error, power). Results Dual-criterion designs
      are discussed for a randomized controlled and a single-arm phase II trial,
      including decision criteria, sample size calculations, decisions under various
      data scenarios, and operating characteristics. The designs facilitate GO/NO-GO
      decisions due to their complementary statistical-clinical criterion. Limitations
      While conceptually simple, implementing a dual-criterion design needs care. The
      clinical DV must be elicited carefully in collaboration with clinicians, and
      understanding similarities and differences to a standard design is crucial.
      Conclusion To improve evidence-based decision-making, a formal yet transparent
      quantitative framework is important. Dual-criterion designs offer an appealing
      statistical-clinical compromise, which may be preferable to standard designs if
      evidence against the null hypothesis alone does not suffice for an efficacy
      claim.

PMID- 30204026
TI  - Providing a Safe Environment in a Psychiatric Ward: Nurses and Vigilance in Iran.
AB  - The aim of this study was to explore nurses' use of vigilance in the provision of
      inpatient psychiatric care. In this qualitative exploratory descriptive design
      study, 16 nurses working in inpatient psychiatric units were recruited through
      purposive sampling. Data were collected by semi-structured interviews and
      fieldwork observations and analysed using conventional content analysis.
      According to participants, nurses' vigilance is related to synthesising
      knowledge, experience, communication, and presence. This conclusion was derived
      from four main themes: understanding the context of the psychiatric ward;
      continuous monitoring; cognitive assessments; and involving others. The study
      highlights the significance of education for all mental health staff and
      provision of appropriate information to all patients and their companions about
      psychiatric disorders and the side effects of prescribed medications. Of
      importance is the skill of active listening to the concerns of patients and the
      demonstration of commitment by nurses to follow-up on reports from stakeholders.
      Imparting the skills and experiences of senior nurses to novice nurses and their
      presence alongside other nurses on work-shifts can be effective in promoting
      vigilance.

PMID- 30204027
TI  - Exploring Expressions of Depression in Black Single Mothers.
AB  - PROBLEM: This study investigates the experience of depression from the
      perspective of Black single mothers, an understudied diverse-sub-group who
      consistently report high levels of depressive symptoms that go undetected and
      untreated. PARTICIPANTS: The sample consisted of 210 Black single mothers aged 18
      45 who reside in urban communities. METHODS: A descriptive, cross-sectional
      design was used to categorize the responses of Black single mothers to an open
      ended question that asks about feelings of depression according to the four
      domains of the Centers for Epidemiologic Studies Depression Scale. Percentages
      and frequencies were used to describe the results of the analysis. FINDINGS: The
      303 usable responses were most consistent with the depressed affect domain (N =
      172), followed by somatic activity (N = 108), interpersonal symptoms (N = 21),
      and lack of positive affect (N = 2). The most prevalent raw responses included
      sadness (N = 59), forms of anger (N = 48), depressed (N = 24), cry (N = 23), do
      not want to be around people (N = 21), lonely (N = 17), tired (N = 16), and
      stressed (N = 12). CONCLUSIONS/IMPLICATIONS: Consider culture and individualized
      assessments to explore feelings of anger and sadness when screening for
      depressive symptoms in specific sub-groups of Black single mothers. Consider the
      use of appropriate screening tools.

PMID- 30204030
TI  - Global Mental Health Initiatives.

PMID- 30204028
TI  - Human inner ear blood supply revisited: the Uppsala collection of temporal bone
      an international resource of education and collaboration.
AB  - BACKGROUND: The Uppsala collection of human temporal bones and molds is a unique
      resource for education and international research collaboration. Micro
      computerized tomography (micro-CT) and synchrotron imaging are used to
      investigate the complex anatomy of the inner ear. Impaired microcirculation is
      etiologically linked to various inner ear disorders, and recent developments in
      inner ear surgery promote examination of the vascular system. Here, for the first
      time, we present three-dimensional (3D) data from investigations of the major
      vascular pathways and corresponding bone channels. METHODS: We used the archival
      Uppsala collection of temporal bones and molds consisting of 324 inner ear casts
      and 113 macerated temporal bones. Micro-CT was used to investigate vascular bone
      channels, and 26 fresh human temporal bones underwent synchrotron radiation phase
      contrast imaging (SR-PCI). Data were processed by volume-rendering software to
      create 3D reconstructions allowing orthogonal sectioning, cropping, and soft
      tissue analyses. RESULTS: Micro-CT with 3D rendering was superior in reproducing
      the anatomy of the vascular bone channels, while SR-PCI replicated soft tissues.
      Arterial bone channels were traced from scala vestibuli (SV) arterioles to the
      fundus, cochlea, and vestibular apparatus. Drainage routes along the aqueducts
      were examined. CONCLUSION: Human inner ear vessels are difficult to study due to
      the adjoining hard bone. Micro-CT and SR-PCI with 3D reconstructions revealed
      large portions of the micro-vascular system in un-decalcified specimens. The
      results increase our understanding of the organization of the vascular system in
      humans and how altered microcirculation may relate to inner ear disorders. The
      findings may also have surgical implications.

PMID- 30204029
TI  - Zebrafish expression reporters and mutants reveal that the IgSF cell adhesion
      molecule Dscamb is required for feeding and survival.
AB  - Down syndrome cell adhesion molecules (DSCAMs) are broadly expressed in nervous
      systems and play conserved roles in programmed cell death, neuronal migration,
      axon guidance, neurite branching and spacing, and synaptic targeting. However,
      DSCAMs appear to have distinct functions in different vertebrate animals, and
      little is known about their functions outside the retina. We leveraged the
      genetic tractability and optical accessibility of larval zebrafish to investigate
      the expression and function of a DSCAM family member, dscamb. Using targeted
      genome editing to create transgenic reporters and loss-of-function mutant
      alleles, we discovered that dscamb is expressed broadly throughout the brain,
      spinal cord, and peripheral nervous system, but is not required for overall
      structural organization of the brain. Despite the absence of obvious anatomical
      defects, homozygous dscamb mutants were deficient in their ability to ingest food
      and rarely survived to adulthood. Thus, we have discovered a novel function for
      dscamb in feeding behavior. The mutant and transgenic lines generated in these
      studies will provide valuable tools for identifying the molecular and cellular
      bases of these behaviors.

PMID- 30204031
TI  - Research on the Effects of Levetiracetam in Spinal Cord Injury Model in Rats: An
      Experimental Study.
AB  - PURPOSE: Despite advances in spinal biomechanic research, surgical techniques,
      and rehabilitation processes, no significant improvement has been identified in
      the treatment of spinal cord injury (SCI) and neurological recovery. AIM OF THE
      STUDY: This study was designed to investigate the potential therapeutic effects
      of methylprednisolone and levetiracetam on SCI. MATERIALS AND METHODS: In this
      study, 42 male Wistar Albino rats, each weighing 300-350 g, were separated into
      three main groups: control group, acute and subacute stage groups. With the
      exception of the control group, a T7-8 dorsal laminectomy was performed on the
      spinal column of the rats. A temporary vascular aneurysm clip was then applied to
      the spinal cord for 1 min to create SCI and methylprednisolone or levetiracetam
      was administered intraperitoneally to all except the control and SHAM control
      groups. The damaged spinal cord was removed for histopathological and biochemical
      examinations. RESULTS: Both pharmacological agents were determined to have
      improved the histopathological architecture in damaged neural tissues during the
      acute period of SCI, but could not sustain this activity in the subacute period.
      Neither pharmacological agent affected the biochemical data in the acute nor
      subacute stages. CONCLUSIONS: Both pharmacological agents showed
      histopathological healing effects in injured tissues during the acute phase of
      SCI in this rat model but these effects could not be sustained in the subacute
      period. No effect on biochemical data was seen in either the acute or subacute
      period. There is a need for further advanced studies to determine the effects of
      levetiracetam on the healing processes in SCI.

PMID- 30204032
TI  - Mini-monoka stenting for patients with perennial allergic conjunctivitis.
AB  - PURPOSE: To assess the effectiveness of mini-monoka (MM) stenting in treating
      patients with perennial allergic conjunctivitis (PAC) and punctal stenosis.
      METHODS: A retrospective case analysis was performed on 20 patients (40 eyes) who
      suffered from PAC with punctal stenosis who underwent MM (FCI Ophthalmics,
      Pembroke, MA, USA) stenting. RESULTS: Nineteen patients (95%) were females, with
      an age range of 19-66 years (average 40.6 +/- 25.4 years). All 20 patients (100%
      of eyes) had signs of PAC and punctal stenosis. All 20 patients (40 eyes) had
      received previous topical treatment including steroids. Nineteen patients (95% of
      eyes) had significant improvement in their allergy symptoms (tearing and
      conjunctival inflammation) following MM stenting. CONCLUSIONS: Stenosis of the
      punctum may play a role in the relapsing symptoms in PAC. MM stenting is a
      simple, safe, effective, and relatively non-invasive treatment option for the
      management of PAC in the presence of punctal stenosis.

PMID- 30204033
TI  - Mental Health Nursing Practice and Indigenous Australians: A Multi-Sited
      Ethnography.
AB  - Criticism of public mental services provided to Indigenous Australians have
      persisted over the last two decades, despite several national reports and
      policies that have attempted to promote positive service change. Mental health
      nurses represent the largest professional group practising within these services.
      This paper reports on a multi-sited ethnography of mental health nursing practice
      as it relates to this group of mental health service users. It explores the
      beliefs and ideas that nurses identified about specialist mental health nursing
      practice and Indigenous Australians. The study found a disunited approach to
      practice during the fieldwork. Practice was expressed as a series of individual
      constructions built upon the nurses' beliefs about Indigenous Australians and
      their experiences in practice with these peoples. The criticism of mental health
      services from Indigenous communities was understandable to the mental health
      nurses, but how they could address this through their individual practices was
      not always clear to them. The actions by public mental health services to improve
      cultural safety through generic training related to the broad area of Indigenous
      health and health service needs, does not appear to evolve into informed
      specialist mental health nursing practice for Indigenous Australian service
      users.

PMID- 30204034
TI  - Psychometric Properties of the Reduced Version of the Glaucoma Treatment
      Compliance Assessment Tool (GTCAT).
AB  - PURPOSE: To measure the psychometric properties of a reduced, 27-statement
      version of the Glaucoma Treatment Compliance Assessment Tool (GTCAT). METHODS: We
      administered the GTCAT to 183 participants who were using a single bottle of an
      ocular hypotensive agent, and objectively measured adherence with Medication
      Event Monitoring System devices over 60 days. Adherence was the number of days
      with correctly timed bottle openings divided by the total number of study days.
      Using the 47-statement GTCAT, we created a reduced GTCAT by removing statements
      that: (1) did not load using Principal Components Analysis (PCA); (2) did not
      have a univariable association with adherence; or (3) were highly correlated (.75
      or higher) with another statement. We assessed the construct validity of the
      remaining statements using PCA and assessed the predictive validity using
      multiple logistic regression analysis. RESULTS: We removed 20 statements because
      they did not appear in the PCA analysis; were not predictive of adherence; and/or
      had high correlation. PCA of the reduced GTCAT (27 statements) extracted 5
      components of the Health Belief Model (knowledge, susceptibility, cues-to-action,
      self-efficacy, and barriers). Multiple regression showed that the 27 statements
      predicted adherence (Rsq = .11, p = .03). CONCLUSIONS: The reduced version of the
      GTCAT is associated with adherence, which suggests that after external
      validation, future glaucoma medication adherence studies could use the reduced
      version to efficiently measure health behaviors and determine the benefit of the
      GTCAT to develop personalized interventions in glaucoma adherence.

PMID- 30204035
TI  - Function of protein kinase CK2 in thrombus formation.
AB  - Thrombus formation is dependent on the interaction of platelets, leukocytes and
      endothelial cells as well as proteins of the coagulation cascade. This
      interaction is tightly controlled by phospho-regulated pathways involving protein
      kinase CK2. A growing number of studies have demonstrated an important role of
      this kinase in the regulation of primary and secondary hemostasis. Inhibition of
      CK2 downregulates the expression of important adhesion molecules on platelets and
      endothelial cells, such as glycoprotein (GP)IIb/IIIa, P-selectin, von Willebrand
      factor and vascular cell adhesion molecule. Moreover, the reduced CK2-dependent
      phosphorylation of different coagulation factors prevents the conversion of
      fibrinogen to fibrin. Targeting these mechanisms may open the door for the
      development of novel anti-thrombotic therapies.

PMID- 30204036
TI  - To save or degrade: balancing proteasome homeostasis to maximize cell survival.
AB  - Autophagic degradation of proteasomes (termed proteaphagy) is a conserved
      mechanism by which cells eliminate excess or damaged particles. This clearance is
      induced rapidly when organisms are starved for nitrogen and, because proteasomes
      are highly abundant, their breakdown likely makes an important contribution to
      the amino acid pools necessary for survival. By contrast, our recent studies
      found that proteasomes are not degraded in response to carbon starvation, even
      though bulk macroautophagy is similarly activated. Instead, carbon starvation
      induces sequestration of proteasomes into membrane-less cytoplasmic condensates
      previously termed proteasome storage granules (PSGs), which protect proteasomes
      from autophagic degradation. Preserving proteasomes in PSGs enhances the ability
      of yeast cells to recover from a variety of stresses, implying that rapid
      remobilization of stored proteasomes when conditions improve is advantageous to
      cell fitness. Consequently, the choice of whether to save or degrade proteasomes
      can profoundly impact cell survival.

PMID- 30204037
TI  - No exchange, same pain, no gain: Risk-reward of wearable healthcare disclosure of
      health personally identifiable information for enhanced pain treatment.
AB  - Wearable technologies have created fascinating opportunities for patients to
      treat chronic pain in a discreet, mobile fashion. However, many of these health
      wearables require patients to disclose sensitive information, including health
      information (e.g., heart rate, glucose levels) and personal information
      (location, email, name, etc.). Individuals using wearables for treatment of
      chronic pain may sacrifice social health elements, including their privacy, in
      exchange for better physical and mental health. Utilizing communication privacy
      management, a popular disclosure theory, this article explores the policy and
      ethical ramifications of patients disclosing sensitive health information in
      exchange for better health treatment and relief of chronic pain. The article
      identifies scenarios where a user must disclose information, and what factors
      motivate or dissuade disclosure, and ultimately the use of a health wearable.
      Practical implications of this conceptual article include an improved
      understanding of how and why consumers may disclose personal data to health
      wearables, and potential impacts for public policy and ethics regarding how
      wearables and their manufacturers entice disclosure of private health
      information.

PMID- 30204038
TI  - Oliguric acute kidney injury after microwave ablation of large liver tumors:
      incidence and preventive measures.
AB  - PURPOSE: Acute kidney injury (AKI), especially oliguric AKI, is a recognized
      complication following microwave ablation (MWA) of large liver tumors. This study
      evaluated the clinical features, mechanisms, risk factors and prevention
      strategies for oliguric AKI after MWA of large liver tumors. METHODS: From March
      2011 to May 2015, 441 patients with liver tumors ?5 cm received MWA in our
      hospital. The clinical features, prevention strategies, further mechanisms and
      possible risk factors for oliguric AKI after MWA were analyzed. RESULTS: One
      hundred four (23.6%) patients had AKI after MWA; 11 (10.6%) patients had oliguric
      AKI, and 93 (89.4%) patients had nonoliguric AKI. All patients with nonoliguric
      AKI recovered without any special treatments. The eleven patients with oliguric
      AKI received appropriate treatments and had completely normal renal function
      three months later. Using double needles for ablation was a risk factor for
      nonoliguric AKI, while high preoperative levels of red blood cells (RBC),
      hemoglobin (HGB) and albumin (Alb) were risk factors for oliguric AKI. The
      decrease levels of hemoglobin were significantly high in oliguric AKI patients (p
      < .05). Patients with oliguric AKI had abnormally high postoperative transaminase
      and renal function indicators. Compared to postoperative prevention,
      intraoperative prevention significantly lowered the occurrence of oliguric AKI
      (0% vs. 3.7%, p = .018) and shortened the hospital stay. CONCLUSIONS: Patients
      who underwent MWA for large liver tumors are prone to develop oliguric AKI.
      Implementation of intraoperative strategies during MWA can effectively prevent
      the occurrence of this severe complication.

PMID- 30204039
TI  - The association between lacunes and white matter hyperintensity features on MRI:
      The SMART-MR study.
AB  - Lacunes and white matter hyperintensities (WMHs) are features of cerebral small
      vessel disease (CSVD) that are associated with poor functional outcomes. However,
      how the two are related remains unclear. In this study, we examined the
      association between lacunes and several WMH features in patients with a history
      of vascular disease. A total of 999 patients (mean age 59 +/- 10 years) with a
      1.5 T brain magnetic resonance imaging (MRI) scan were included from the SMART-MR
      study. Lacunes were scored visually and WMH features (volume, subtype and shape)
      were automatically determined. Analyses consisted of linear and Poisson
      regression adjusted for age, sex, and total intracranial volume (ICV). Patients
      with lacunes (n = 188; 19%) had greater total (B = 1.03, 95% CI: 0.86 to 1.21),
      periventricular/confluent (B = 1.08, 95% CI: 0.89 to 1.27), and deep (B = 0.71,
      95% CI: 0.44 to 0.97) natural log-transformed WMH volumes than patients without
      lacunes. Patients with lacunes had an increased risk of confluent type WMHs (RR =
      2.41, 95% CI: 1.98 to 2.92) and deep WMHs (RR = 1.41, 95% CI: 1.22 to 1.62) and
      had a more irregular shape of confluent WMHs than patients without lacunes,
      independent of total WMH volume. In conclusion, we found that lacunes on MRI were
      associated with WMH features that correspond to more severe small vessel changes,
      mortality, and poor functional outcomes.

PMID- 30204040
TI  - Breath hold effect on cardiovascular brain pulsations - A multimodal magnetic
      resonance encephalography study.
AB  - Ultra-fast functional magnetic resonance encephalography (MREG) enables separate
      assessment of cardiovascular, respiratory, and vasomotor waves from brain
      pulsations without temporal aliasing. We examined effects of breath hold- (BH)
      related changes on cardiovascular brain pulsations using MREG to study the
      physiological nature of cerebrovascular reactivity. We used alternating 32 s BH
      and 88 s resting normoventilation (NV) to change brain pulsations during MREG
      combined with simultaneously measured respiration, continuous non-invasive blood
      pressure, and cortical near-infrared spectroscopy (NIRS) in healthy volunteers.
      Changes in classical resting-state network BOLD-like signal and cortical blood
      oxygenation were reproduced based on MREG and NIRS signals. Cardiovascular
      pulsation amplitudes of MREG signal from anterior cerebral artery, oxygenated
      hemoglobin concentration in frontal cortex, and blood pressure decreased after
      BH. MREG cardiovascular pulse amplitudes in cortical areas and sagittal sinus
      increased, while cerebrospinal fluid and white matter remained unchanged.
      Respiratory centers in the brainstem - hypothalamus - thalamus - amygdala network
      showed strongest increases in cardiovascular pulsation amplitude. The spatial
      propagation of averaged cardiovascular impulses altered as a function of
      successive BH runs. The spread of cardiovascular pulse cycles exhibited a
      decreasing spatial similarity over time. MREG portrayed spatiotemporally accurate
      respiratory network activity and cardiovascular pulsation dynamics related to BH
      challenges at an unpreceded high temporal resolution.

PMID- 30204041
TI  - Unraveling structural requirements of amino-pyrimidine T790M/L858R double mutant
      EGFR inhibitors: 2D and 3D QSAR study.
AB  - EGFR is an important drug target in cancer. However, the ineffectiveness of first
      generation inhibitors due to the occurrence of a secondary mutation (T790M)
      results in the relapse of the disease. Identification of reversible inhibitors
      against T790M/L858R double mutants (TMLR) thus is a foremost requirement. In this
      study, various 2 D and 3 D Quantitative Structure-Activity Relationship models
      were built for amino-pyrimidine compounds with their known biological activity
      against TMLR mutants. The model developed using multiple linear regression
      statistical method via stepwise forward-backward variable selection technique
      showed the best results in terms of internal and external predictivity. The 2D
      QSAR model indicated that the presence of electronegative atom, H-bond donors,
      moderate slogp, count of number of N atoms separated from O (T_N_O_4),
      4pathClusterCount and number of S atom connected with two single bonds (SssSE
      index), is required for increasing the inhibitory potential of compounds. Also,
      the 3D-QSAR model suggested that electronegative group at certain positions along
      with the presence of bulky groups is beneficial for good inhibition activity of
      the compounds. Thus, the QSAR models developed in the present work can be used
      for predicting the TMLR bioactivity of a new series of amino-pyrimidine
      derivatives. To the best of the author's knowledge, this is the first study which
      deals with the development of 2 D and 3D-QSAR models for double mutant TMLR
      inhibitors.

PMID- 30204042
TI  - The platelet aggregometer and beyond: Gustav Born at the Royal College of
      Surgeons.
AB  - In 1960, Gustav Born was appointed to head the Department of Pharmacology at the
      Royal College of Surgeons in London. The next 13 years  would prove to be  the
      most productive in his scientific career and the most important in the
      development of the Department into an internationally respected research center.
      The advances in platelet biology were made possible by the evolution of the
      platelet aggregometer, brilliantly conceived and developed by Born and his team,
      into a robust and reliable scientific instrument, with which they, quite
      literally, revolutionized the study of platelet function. For the first time, the
      actions of agonists and antagonists could be quantified pharmacologically, and
      the biochemistry of aggregation analyzed, identifying two systems, cyclic
      nucleotides and phospholipid metabolism, as crucial to the understanding of the
      pathophysiology of human platelets. Recognizing the critical importance of the
      interplay between platelets, leucocytes and the vascular endothelium, in the
      formation and in the rupture of atheromatous plaques, his group also investigated
      aggregation in the microvasculature in vivo. Born's never-ending flow of ideas
      and enthusiasm for their exploration created an atmosphere of discovery in his
      group that matched that of his colleague, John Vane. It was a collaboration
      between these two teams that elucidated the mechanism of action of the non
      steroidal anti-inflammatory drugs (NSAIDs) and established the prophylactic use
      of aspirin as an anti-thrombotic therapy - indeed, two of the most significant
      pharmacological discoveries of the twentieth century.

PMID- 30204043
TI  - Canadian older adults' perceptions of effectiveness and value of regular and high
      dose influenza vaccines.
AB  - Influenza vaccination is an important public health intervention for older
      adults, yet vaccination rates remain suboptimal. We conducted an online survey of
      Canadians >= 65 years to explore satisfaction with publicly-funded standard-dose
      influenza vaccines, and perceptions of the need for a more effective product.
      They were provided with information about currently approved influenza vaccines,
      and were asked about their preferences should all formulations be available for
      free, and should the recently approved high-dose (HD) vaccine for seniors be
      available at a cost. From March to April 2017, 5014 seniors completed the survey;
      mean age was 71.3 +/- 5.17 years, 50% were female, and 42.6% had one or more
      chronic conditions. 3403 (67.9%) had been vaccinated against influenza in the
      2016/17 season. Of all respondents, 3460 (69%) were satisfied with the standard
      dose influenza vaccines, yet 3067 (61.1%) thought that a more effective vaccine
      was/may be needed. If HD was only available at a cost, 1426 (28.4%) respondents
      would consider it, of whom 62.9% would pay $20 or less. If all vaccines were free
      next season, 1914 (38.2%) would opt for HD (including 12.2% of those who
      previously rejected influenza vaccines), 856 (17.1%) would choose adjuvanted
      vaccine, and 558 (11.1%) standard-dose vaccine. 843 (16.8%) of respondents were
      against vaccines, 451 (9.0%) had no preference and 392 (7.8%) were uncertain.
      Making this product available through publicly funded programs may be a strategy
      to increase immunization rates in this population.

PMID- 30204044
TI  - Spatiotemporal analysis of impaired microglia process movement at sites of
      secondary neurodegeneration post-stroke.
AB  - It has recently been identified that after motor cortex stroke, the ability of
      microglia processes to respond to local damage cues is lost from the thalamus, a
      major site of secondary neurodegeneration (SND). In this study, we combine a
      photothrombotic stroke model in mice, acute slice and fluorescent imaging to
      analyse the loss of microglia process responsiveness. The peri-infarct
      territories and thalamic areas of SND were investigated at time-points 3, 7, 14,
      28 and 56 days after stroke. We confirmed the highly specific nature of non
      responsive microglia processes to sites of SND. Non-responsiveness was at no time
      observed at the peri-infarct but started in the thalamus seven days post-stroke
      and persisted for 56 days. Loss of directed process extension is not a reflection
      of general functional paralysis as phagocytic function continued to increase over
      time. Additionally, we identified that somal P2Y12 was present on non-responsive
      microglia in the first two weeks after stroke but not at later time points.
      Finally, both classical microglia activation and loss of process extension are
      highly correlated with neuronal damage. Our findings highlight the importance of
      microglia, specifically microglia dynamic functions, to the progression of SND
      post-stroke, and their potential relevance as modulators or therapeutic targets
      during stroke recovery.

PMID- 30204045
TI  - Comparison of platelet function tests for the in vitro quality assessment of
      platelet concentrates produced under real-life conditions.
AB  - Platelet quality in different platelet concentrates (PCs) has been the subject of
      several studies. Nonetheless, there is a lack of robust data on the correlation
      and agreement among platelet function tests as a prerequisite for the association
      of PC functionality in vitro with platelet function in vivo post PC transfusion.
      The purpose of our study was to correlate a larger panel of platelet function
      assays in PCs and to assess whether the methods agree sufficiently and can be
      used interchangeably. Twelve apheresis platelet concentrates in plasma (APC), 16
      pooled platelet concentrates in plasma (PPC), and 12 PPC in T-sol (PPCA) were
      examined on days 1 and 4 after production. PCs were tested for platelet count,
      light transmission aggregation (LTA) induced by ADP, collagen, or TRAP; platelet
      ATP release induced by collagen; and spontaneous and ADP and TRAP-induced
      increase in CD62P and PAC1 expression measured by flow cytometry. All tests were
      performed in undiluted platelet-rich plasma, recalcified and mixed with an
      inhibitor of factor Xa and thrombin. Most platelet function parameters correlated
      significantly with each other, but agreement among methods was insufficient. A
      proper inverse correlation was observed between ADP-induced LTA and spontaneous
      platelet activation assessed by CD62P expression (r = -0.61, p < 0.0001).
      Spontaneous CD62P correlated also significantly with spontaneous PAC1 (r = 0.69,
      p < 0.0001) and inversely with TRAP-induced CD62P expression (r = -0.86, p <
      0.0001). We found significant correlations among all flow cytometric assays
      measuring platelet CD62P and PAC1 expression induced by ADP or TRAP. Subsequent
      Bland Altman analysis revealed insufficient agreement between methods. With one
      exception (collagen-induced LTA compared with TRAP-induced LTA, percentage error
      = 16%) the limits of agreement expressed as percentage error exceeded the chosen
      acceptable difference of 30%. In APC, platelet count was 41% and 44% higher,
      respectively, than in PPC and PPCA (p < 0.0001). Spontaneous CD62P and PAC1
      expression were significantly greater, and ADP-induced aggregation and agonist
      induced increase in CD62P and PAC1 were significantly lower in PPCA compared to
      APC and PPC on day 4 of storage. ADP and TRAP-induced CD62P and PAC1
      activatability fell significantly during storage between day 1 and day 4 in APC
      and PPCA, but not in PPC. In conclusion, different platelet function tests
      capture different aspects of platelet function and do not correlate and agree
      sufficiently to be used interchangeably.

PMID- 30204046
TI  - Platelets and cancer: pathology and drug targets.

PMID- 30204047
TI  - Therapeutic Relationships and Safety of Care in Iranian Psychiatric Inpatient
      Units.
AB  - Enhancing therapeutic relationships between patients and staff is of central
      importance to improve the quality and safety of care in psychiatric inpatient
      units. However, there is limited evidence as to how therapeutic relationships may
      be enabled in this specific context. This paper presents findings of a study that
      explored the link between therapeutic relationships and safety in Iranian
      psychiatric inpatient units. In this exploratory, descriptive study, seven
      patients at the point of discharge and 19 staff in psychiatric inpatient units in
      Iran were interviewed regarding their experiences of care. The quality of staff
      patient relationship in providing a safe environment was categorized into two
      groups of "facilitators" and "inhibitors". Facilitators of a safe environment
      included "supportive relationship with patients" and "improving patient capacity
      for self-efficacy/self-control". Inhibitors, on the other hand, included
      "detachment from patients" and "domination over patients", which ultimately
      limited safety on the ward. Findings indicate interrelated environmental, patient
      and staff factors mediating the potential for therapeutic relationships and
      quality and safety of care. Findings suggest the need for more effective
      preparation and support for staff working within psychiatric inpatient settings.
      In addition, environments more conducive to collaborative recovery-oriented
      practice are required to enhance therapeutic relationships and improve quality
      and safety of care. Both individual staff responsibility and effective leadership
      are required to realize change.

PMID- 30204049
TI  - In silico screening of deleterious single nucleotide polymorphisms (SNPs) and
      molecular dynamics simulation of disease associated mutations in gene responsible
      for Oculocutaneous Albinism type 6 (OCA 6) disorder.
AB  - Solute carrier family 24 member 5 (SLC24A5) is a gene that is associated with
      Oculocutaneous albinism type 6 (OCA 6) disorder and is involved in skin and hair
      pigmentation. It is involved in the maturation of melanosomes and melanin
      synthesis. SLC24A5 gene is located in the chromosomal position of 15q21.1. The
      present study involves the use of computational techniques in order to obtain a
      detailed picture of the most probable mutations that are associated with SLC24A5.
      From the observed result it was found that the mutations S145F is most
      deleterious and disease associated predicted by using several bioinformatics
      tools. The 3-D structures of native and mutant (S145F) were modelled in order to
      understand protein functionality using ab initio Robetta server. The modelled
      structure validation was done with ERRAT, Verify-3D, Procheck and RAMPAGE
      Ramachandran plot analysis. The most validated structure undergoes molecular
      dynamics simulations (MDS) study to understand the structural and functional
      behaviour of the native and mutant proteins. The mds result showed the more
      flexibility in the native SLC24A5 structure. Due to mutation in the SLC24A5
      protein structure it became more rigid and might disturb the conformational
      changes and glycosylation function of protein structure and might play role in
      inducing the OCA 6. This study provides a significant insight into the underlying
      molecular mechanism involved in albinism associated with OCA 6. It further helps
      scientists to develop a drug therapy against OCA 6 disease.

PMID- 30204048
TI  - Establishment of peripheral blood mononuclear cell-derived humanized lung cancer
      mouse models for studying efficacy of PD-L1/PD-1 targeted immunotherapy.
AB  - Animal models used to evaluate efficacies of immune checkpoint inhibitors are
      insufficient or inaccurate. We thus examined two xenograft models used for this
      purpose, with the aim of optimizing them. One method involves the use of
      peripheral blood mononuclear cells and cell line-derived xenografts (PBMCs-CDX
      model). For this model, we implanted human lung cancer cells into NOD-scid-IL2Rg
      /- (NSI) mice, followed by injection of human PBMCs. The second method involves
      the use of hematopoietic stem and progenitor cells and CDX (HSPCs-CDX model). For
      this model, we first reconstituted the human immune system by transferring human
      CD34+ hematopoietic stem and progenitor cells (HSPCs-derived humanized model) and
      then transplanted human lung cancer cells. We found that the PBMCs-CDX model was
      more accurate in evaluating PD-L1/PD-1 targeted immunotherapies. In addition, it
      took only four weeks with the PBMCs-CDX model for efficacy evaluation, compared
      to 10-14 weeks with the HSPCs-CDX model. We then further established PBMCs
      derived patient-derived xenografts (PDX) models, including an auto-PBMCs-PDX
      model using cancer and T cells from the same tumor, and applied them to assess
      the antitumor efficacies of anti-PD-L1 antibodies. We demonstrated that this
      PBMCs-derived PDX model was an invaluable tool to study the efficacies of PD
      L1/PD-1 targeted cancer immunotherapies. Overall, we found our PBMCs-derived
      models to be excellent preclinical models for studying immune checkpoint
      inhibitors.

PMID- 30204050
TI  - Delayed processing of global shape information is associated with weaker top-down
      effects in developmental prosopagnosia.
AB  - In previous studies we have shown that a group of individuals with developmental
      prosopagnosia (DP): (i) were impaired at recognizing objects when presented as
      silhouettes or fragmented forms; stimuli which place particular demands on global
      shape processing, (ii) that these impairments correlated with their face
      recognition deficit, (iii) that they showed a reduced global precedence effect in
      Navon's paradigm, and (iv) that the magnitude of their global precedence effect
      correlated with their face and object recognition performance. This pattern of
      deficits points towards a delay in the processing of global shape information; a
      delay that may weaken top-down influences on recognition performance. Here we
      show that the DPs show reduced real object superiority effects (faster responses
      to real objects than nonobjects) compared with controls. Given that real object
      superiority effects reflect top-down processing, these findings support the
      notion of impaired global shape based top-down processing in DP.

PMID- 30204051
TI  - First Report of Alfalfa Leaf Curl Virus from Alfalfa in Iran.

PMID- 30204052
TI  - Homology modeling of human histone deacetylase 10 and design of potential
      selective inhibitors.
AB  - Histone deacetylases (HDACs) are implicated in the pathology of various cancers
      and their pharmacological blockade has proven to be promising in reversing the
      malignant phenotypes. However, lack of crystal structures of some of the human
      HDAC isoforms (e.g., HDAC10) hinders the desgn of isoform-selective inhibitor.
      Here, the recently-solved X-ray crystal structure of Danio rerio (zebrafish)
      HDAC10 (PDB ID; 5TD7, release date 24-05-2017) was retrieved from the Protein
      Data Bank (PDB) and used as a template structure to model the 3D structure of
      human HDAC10. The overall quality of the best model (M0017) was assessed by
      computing its z-score - a measure of the deviation of the total energy of the
      structure with respect to an energy distribution derived from random
      conformations, and by docking of known HDAC10 inhibitors to its catalytic cavity.
      Furthermore, to identify potential HDAC10-selective inhibitors ligand-based
      virtual screening was carried out against ZINC database. The free modeled
      structure of HDAC10, and its complexes with quisinostat and the highest-ranked
      compound, ZINC19749069 were submitted to molecular dynamics simulation.
      Comparative analysis of root-mean-squared deviation (RMSD), root-mean-squared
      fluctuation (RMSF), radius of gyration (Rg), and potential energy of these
      systems showed that HDAC10-ZINC19749069 complex remained the most stable over
      time. Thus, M0017 could be potentially used for structure-based inhibitor against
      HDAC10, and ZINC19749069 may provide a scaffold for further optimization.

PMID- 30204053
TI  - Molecular detection of equine trypanosomiasis in the Riyadh Province of Saudi
      Arabia.
AB  - We conducted a cross-sectional study to detect trypanosome infections of horses
      and donkeys in the Riyadh Province of Saudi Arabia. DNA was extracted from blood
      samples collected from 368 horses and 142 donkeys, and subjected to universal
      first ribosomal internal transcribed spacer region (ITS1)-PCR followed by
      Trypanosoma evansi species-specific RoTat1.2-PCR. The universal ITS1-PCR revealed
      T. evansi infection in horses ( n = 12; 3.3%) and donkeys ( n = 4; 2.8%). There
      was no significant effect of sex or age on the prevalence of trypanosomiasis in
      horses or donkeys. Application of the RoTat1.2-PCR revealed that the RoTat1.2 VSG
      gene was absent from the positive ITS1-PCR samples of 3 horses and 1 donkey. This
      discrepancy could be explained by the circulation of T. evansi type B in Saudi
      Arabia; however, this suspicion requires confirmation.

PMID- 30204055
TI  - In silico insights on Tankyrase protein: a potential target for colorectal
      cancer.
AB  - The Wnt/beta-catenin pathway plays an important regulatory role in cancer
      signaling and cell regenerative mechanisms. Its suppression has long been
      considered as an important challenge of anti-cancer treatment and management. The
      poly(ADP-ribose) polymerase (PARP) family represented as a new class of
      therapeutic targets with diverse potential disease indications. Tankyrase (TNKS)
      is considered to be a potential target for the intervention of various cancers.
      The main objective of the work is to explore the molecular and quantum mechanics
      of the drug-like compounds and to identify the potential inhibitors for tankyrase
      protein using the structure and ligand-based virtual screening from several
      databases and to explore the binding pocket and interactions of active residues.
      The screened compounds were further filtered using binding free energy
      calculation and molecular dynamics simulation studies. The results have provided
      a strong molecular knowledge of TNKS and offered top hit potent inhibitors. The
      identified lead compounds LC_40781, LC_40777, LC_39767, LC_8346, NCI_682438, and
      NCI_721141 was observed to have potent activity against TNKS protein. The
      hydrogen bonding of compounds with Asp1198, His1201, Tyr1203 in TNKS1 and
      Gly1032, Ser1068 in TNKS2 are the key interactions plays a major role in binding
      energy. Therefore, the outcome of the study would help for further validation and
      provides valuable information to guide the future tankyrase-specific inhibitor
      designing.

PMID- 30204054
TI  - Nucleic acid nanomedicines in Phase II/III clinical trials: translation of
      nucleic acid therapies for reprogramming cells.
AB  - This review presents an integrated analysis of the current-state-of-the-art in
      nucleic acid nanotherapies and highlights the importance of nanotechnology in the
      delivery of nucleic acid therapies. While there is no one dominant nanodesign,
      the diversity of nanodesigns and delivery of different siRNAs, miRNA and DNA to
      inhibit more than 20 targets in seven disease states in Phase II/III clinical
      trials reflects the potential of nucleic acid therapies to treat intractable
      diseases and non-druggable targets. We provide benchmarks to aid in comparing the
      design, proof-of-concept studies and clinical trials. From this, we demonstrate
      the importance of generating a strategic framework for integrating clinical 'wish
      lists' for a means to treat intractable diseases with engineering 'design
      checklists' for nucleic acid nanotherapies.

PMID- 30204056
TI  - Embryonal central nervous system tumor in the brain of a goose.
AB  - Embryonal central nervous system (CNS) tumor is a rare malignant neoplasm that
      arises from the neural crest. Herein we describe an embryonal tumor in the brain
      of an adult male domestic goose ( Anser anser) that was euthanized after a short
      history of wandering and lethargy. Grossly, a focal, bright-red, soft plaque was
      present on the ventral aspect of the brain, extending from the optic chiasm to
      the midbrain, as well as into the dorsal neuroparenchyma. Histologically, the
      nodule consisted of a poorly demarcated population of neoplastic cells arranged
      in streams and bundles, and occasionally palisading around small capillaries
      (pseudorosettes). Neoplastic cells were elongate and had scant, finely granular,
      eosinophilic cytoplasm, and elongate nuclei with dense chromatin. Mitoses were
      uncommon. Scattered foci of intratumoral necrosis and microvascular proliferation
      were present. Neoplastic cells were immunoreactive for doublecortin and neuronal
      nuclei. Ultrastructurally, neoplastic cells had elongated-to-polyhedral cytoplasm
      with short processes, scarce intermediate filaments, and small round mitochondria
      and rough endoplasmic reticulum. The cell membrane had varied numbers of
      intercellular anchoring-like junctions, and nuclei were round-to-elongate and had
      marginal aggregates of heterochromatin. Morphologic, immunohistochemical, and
      ultrastructural findings in our case are consistent with a poorly differentiated
      embryonal tumor.

PMID- 30204058
TI  - Retrospective comparison of standard clotting tests and novel clot waveform
      parameters in dogs using the turbidimetric ACL-TOP CTS 300 coagulation analyzer.
AB  - Clot waveforms are generated by coagulation analyzers, such as the ACL-TOP, that
      utilize photo-optical turbidimetric methods to measure prothrombin time (PT) and
      activated partial thromboplastin time (aPTT), which are standard clotting tests
      (SCTs). Additional quantitative clot waveform analysis (CWA) parameters include
      maximum velocity of the PT curve (PT1d), maximum acceleration of the aPTT curve
      (aPTT2d), and their change in optical density (ODdelta). We explored the
      potential for CWA to contribute unique information compared to SCTs and
      quantitative fibrinogen assay (QFA) in dogs with clinical indications for
      laboratory evaluation of coagulation. We retrospectively evaluated the frequency
      and agreement between normal, high, and low values of CWA and SCTs for 203 dogs
      relative to reference intervals (RIs). Most dogs had SCTs within RIs, but most
      CWA values were high regardless of whether SCT values were within, below, or
      above the RI. Agreement between SCTs and CWA was slight (kappa <30%). Clinically
      significant bleeding was noted in 28 of 203 (14%) dogs. SCTs were not different
      between bleeders and non-bleeders. Median QFA, PT1d, aPTTdelta, and aPTT2d values
      were statistically significantly higher than RIs in non-bleeders compared to
      bleeders, whose median values were not below RI. Compared with SCTs, CWA
      identified differences between the 2 groups. However, wide overlap between the 2
      groups limits the use of CWA to clinically discriminate between bleeders and non
      bleeders in a heterogeneous population of dogs. Further studies on the diagnostic
      utility of CWA in coagulopathic dogs are needed.

PMID- 30204057
TI  - Congenital abnormalities in calves associated with Peaton virus infection in
      Japan.
AB  - Peaton virus (PEAV; family Peribunyaviridae, genus Orthobunyavirus) appears to be
      capable of producing congenital malformations in ruminants; however, its
      pathogenicity remains unknown given its relatively low incidence. We evaluated
      the relationship between congenital abnormalities of calves and PEAV infection by
      serologic, epidemiologic, pathologic, and virologic investigations using
      specimens from 31 malformed calves in the years 1996-2016 in Japan. Antibody
      testing was carried out for known teratogenic viruses, including Akabane, Aino,
      Chuzan, and bovine viral diarrhea viruses, in the precolostral sera of these
      abnormal calves, but all results were negative. However, all 31 malformed calves
      were positive for antibodies against PEAV. A PEAV-specific gene was amplified
      from central nervous system tissues from a stillborn calf delivered in April
      2007, and its nucleotide sequence was identical with that of PEAV isolated from
      healthy sentinel cattle in September 2006. These findings indicate that PEAV can
      cause bovine congenital anomalies.

PMID- 30204059
TI  - The effect of chemical clarification of oral fluids on porcine epidemic diarrhea
      virus antibody responses.
AB  - Routine testing of breeding herd oral fluid (OF) samples for porcine epidemic
      diarrhea virus (PEDV) IgG and/or IgA is used to track levels of PEDV immunity
      over time. However, OFs contain particles of feed, feces, and inorganic material
      that detract from the quality of the sample. We clarified swine OF samples using
      lyophilized chitosan-based formulas (A-C) tested by PEDV IgG and IgA ELISAs. To
      evaluate both the immediate and residual effects of treatment on antibody
      detection, samples were tested immediately post-treatment, then stored at 4
      degrees C and retested at 2, 4, and 6 days post-treatment (DPT). Formulations
      were shown to effectively clarify samples. Statistical analysis comparing treated
      to untreated OF samples at 0 DPT found that neither chitosan nor Tween 20
      affected the OF ELISA IgA and IgG sample-to-positive (S/P) ratio results ( p >
      0.05). Furthermore, pairwise comparisons of 0 DPT to 2, 4, and 6 DPT results
      detected no significant differences ( p > 0.05) in IgA and IgG S/P ratios (i.e.,
      treated OF samples were stable over time). Therefore, chitosan efficiently
      clarified OF specimens without affecting the results of the PEDV IgG and IgA
      antibody ELISAs.

PMID- 30204060
TI  - Valorization of poly(lactic acid) wastes via mechanical recycling: Improvement of
      the properties of the recycled polymer.
AB  - Poly(lactic acid) (PLA) is a biobased polymer that represents one of the most
      interesting alternatives to fossil-fuel based polymers in food packaging
      applications. Most of the PLA used in food packaging is used only once and then
      discarded, even though the PLA types used in packaging have good properties and
      stability. Therefore, it seems reasonable to consider the possibility of
      recycling the used polymer through a mechanical recycling process. The main aims
      of this work are to study the effect of the mechanical recycling on the
      properties of PLA and the usefulness of different upgrading methods to obtain
      recycled PLA with improved properties. A commercial type of PLA was subjected to
      accelerated thermal, photochemical and hydrolytic aging and then reprocessed.
      During reprocessing, aged PLA was blended with virgin PLA and a commercial chain
      extender was added. Results point out that recycling causes the degradation of
      PLA, and negatively affects the thermal stability and mechanical properties.
      However, addition of virgin PLA, and the chain extender, led to an increase of up
      to 9% in the intrinsic viscosity and 8% in the Vickers hardness of the recycled
      material. These results suggest that mechanically recycled PLA with improved
      performance can be obtained, a fact which might improve the recyclability of PLA
      and thus the environmental impact of this material.

PMID- 30204061
TI  - Eating together as a social network intervention for people with mild
      intellectual disabilities: a theory-based evaluation.
AB  - PURPOSE: People with mild intellectual disabilities (MID) generally live
      independently among the wider community. This can result in social exclusion and
      feelings of loneliness. Therefore, social work organizations aim to socially
      include people with MID through organizing activities in neighbourhoods that
      should lead to enlarged networks and increased societal participation. The
      "Communal Table" is such a, group-orientated, intervention that organizes monthly
      dinners in Amsterdam, the Netherlands. Because little is known about the
      effectiveness of interventions aiming to bring about social inclusion for people
      with MID we explored which types of participants were reached and whether and how
      the intervention brought about the intended outcomes. METHODS: We performed a
      theory-based evaluation, using participatory observations and qualitative
      interviews (n = 19). The Communal Table attracted a diverse and loyal group of
      participants. RESULTS: We distinguished four types of participants-lonely
      participants, activist participants, satisfied participants and calculating
      participants-whose pre-existing networks played a significant role in their
      individual needs for support and the outcomes of the intervention. Outcomes
      reported included experiences of conviviality and warmth, temporary relief of
      underlying problems and an overall positive opinion about the intervention, but
      network enlargement or increased societal participation were not reported.
      CONCLUSIONS: Our findings suggest that social network interventions for people
      with MID should be tailored to participants' pre-existing networks and related
      individual needs to be successful.

PMID- 30204062
TI  - EXPRESS: Case series of seven women with uterine fibroids associated with venous
      thromboembolism and chronic thromboembolic disease.

PMID- 30204064
TI  - Evaluation of lauroyl-gemcitabine-loaded hydrogel efficacy in glioblastoma rat
      models.
AB  - AIM: Anticancer drug-loaded hydrogels are a promising strategy for the local
      treatment of incurable brain tumors such as glioblastoma (GBM). Recently, we
      demonstrated the efficacy of lauroyl-gemcitabine lipid nanocapsule hydrogel
      (GemC12-LNC) in a U-87 MG xenograft orthotopic mouse model. In this study, we
      developed a reliable and reproducible surgical procedure to resect orthotopic GBM
      tumors in rats. GemC12-LNC hydrogel integrity was tested after brain
      administration in rats and its anti-tumor efficacy was tested on a 9L syngeneic
      orthotopic model. RESULTS: We demonstrated that LNC integrity is maintained at
      least for one week after local administration of GemC12-LNC. GemC12-LNC was able
      to delay the formation of recurrences in 9L tumor-bearing resected rats,
      demonstrating the efficacy of this nanomedicine hydrogel in this preclinical
      model. CONCLUSION: Our results confirm that GemC12-LNC, a hydrogel uniquely
      formed by a nanocarrier and a cytotoxic drug, could be a promising and safe
      delivery tool for the local treatment of operable GBM tumors.

PMID- 30204063
TI  - Are localized prostate cancer biomarkers useful in the clinical practice?
AB  - Prostate cancer presents itself in a heterogeneous way with both aggressive and
      indolent forms. Despite the controversy surrounding its use, prostate-specific
      antigen screening ultimately leads to a greater number of diagnosed patients. One
      of the biggest challenges in clinical practice is to select the right patients
      for biopsy and, among diagnosed patients, to differentiate tumors with an
      indolent course from those with an unfavorable prognosis, in order to determine
      the best therapeutic decision for each case, avoiding unnecessary interventions.
      Currently, several types of biomarkers are available for clinical use in patients
      with prostate cancer, which include blood-based (prostate-specific antigen,
      Prostate Health Index(r), 4K score(r)); urine sample-based (PCA3, SelectMDx(r),
      ExoDx Prostate IntelliScore(r)); and biopsy, transurethral resection, or radical
      prostatectomy tissue-based (ConfirmMDx(r), Oncotype(r), Prolaris(r),
      Decipher(r)). The aim of this review is to provide an overview of the current
      state of evidence and to highlight recent advances in the evaluation and
      diagnosis of prostate cancer, with emphasis on biomarkers related to diagnosis
      and to prognostic evaluation of localized prostate cancer.

PMID- 30204065
TI  - A Single Effector Protein, AvrRpt2EA, from Erwinia amylovora Can Cause Fire
      Blight Disease Symptoms and Induces a Salicylic Acid-Dependent Defense Response.
AB  - The AvrRpt2EA effector protein of Erwinia amylovora is important for pathogen
      recognition in the fire blight-resistant crabapple Malus * robusta 5; however,
      little is known about its role in susceptible apples. To study its function in
      planta, we expressed a plant-optimized version of AvrRpt2EA driven by a heat
      shock-inducible promoter in transgenic plants of the fire blight-susceptible
      cultivar Pinova. After induced expression of AvrRpt2EA, transgenic lines showed
      shoot necrosis and browning of older leaves, with symptoms similar to natural
      fire blight infections. Transgenic expression of this effector protein resulted
      in an increase in the expression of the salicylic acid (SA)-responsive PR-1 gene
      but, also, in the levels of SA and its derivatives, with diverse kinetics in
      leaves of different ages. In contrast, no increase of expression levels of VSP2
      paralogs, used as marker genes for the activation of the jasmonic acid (JA)
      dependent defense pathway, could be detected, which is in agreement with
      metabolic profiling of JA and its derivatives. Our work demonstrates that
      AvrRpt2EA acts as a virulence factor and induces the formation of SA and SA
      dependent systemic acquired resistance.

PMID- 30204066
TI  - Real-time PCR assay for screening Pneumocystis in free-living wild squirrels and
      river rats in Italy.
AB  - We used a real-time PCR (rtPCR) targeting a 150-bp amplicon of the mitochondrial
      small subunit of ribosomal RNA (mtSSU rRNA) to screen for Pneumocystis DNA in
      lungs of wild squirrels ( Callosciurus finlaysonii, n = 85) and river rats (
      Myocastor coypus, n = 43) in Italy. The rtPCR revealed Pneumocystis DNA in 20 of
      85 (24%) squirrels and in 35 of 43 (81%) river rats, and was more sensitive than
      a nested PCR that targets a portion of the mtSSU rRNA and the mitochondrial large
      subunit of rRNA (mtLSU rRNA). Phylogenetic analysis based on mtSSU rRNA and mtLSU
      rRNA sequences showed distinct Pneumocystis sequence types in these rodents. The
      rtPCR assay should be reliable for screening large populations for this potential
      pathogen, thereby allowing cost-effective monitoring of the disease in wild
      animals.

PMID- 30204068
TI  - ?

PMID- 30204069
TI  - ?

PMID- 30204067
TI  - A brief review of monoclonal antibody technology and its representative
      applications in immunoassays.
AB  - : Modern immunoassay methods and techniques are important tools in labs of basic
      biology, biomedicine, clinical medicine, and even in home tests, such as pregnant
      test, many of which utilize antibody-antigen binding mechanism as their
      foundational principle in common. Meanwhile, compared with polyclonal anitbody,
      monoclonal antibody shows obvious advantages in their application of modern
      immunoassays. Furthermore, the progress of other technologies have also promoted
      the development of modern immunoassays robustly, and widely made it extend into
      more research and industry fields. In this review, we will first look back to the
      discovery of antibody-antigen binding mechanism, antibody structure, and the
      development of monoclonal antibody technology. Then, a brief description of
      different classical immunoassays will be introduced, such as enzyme-linked
      immunosorbent assay, flow cytometry, Immunoprecipitation, and lateral flow
      immunoassays, through of which, we hope a brief and clear picture can be
      displayed in front of readers. ABBREVIATIONS: ELISA: Enzyme-Linked Immunosorbent
      Assay; WB: western blot; Mab: monoclonal antibody; IP: immunoprecipitation;
      LFIAs: lateral flow immunoassays.

PMID- 30204070
TI  - ?

PMID- 30204071
TI  - ?

PMID- 30204072
TI  - ?

PMID- 30204074
TI  - Can Resting-State Functional MRI Predict Response to Cholinesterase Inhibitors in
      Individuals with Cognitive Impairment?

PMID- 30204073
TI  - Dual-Energy CT Angiography for Detection of Pulmonary Emboli: Incremental Benefit
      of Iodine Maps.
AB  - Purpose To determine if there is added benefit of using iodine maps from dual
      energy (DE) CT in addition to conventional CT angiography images to diagnose
      pulmonary embolism (PE). Materials and Methods In this retrospective analysis,
      1144 consecutive dual-energy CT angiography examinations performed from January
      through September 2014 at an oncologic referral center to evaluate for PE were
      reviewed. The 1144 examinations included 1035 patients (mean age, 58.7 years;
      range, 15-99 years). First, the location, level, and type (occlusive vs
      nonocclusive) of PEs on conventional CT angiograms were recorded. Iodine maps
      were then reviewed for defects suggestive of PE. Last, CT angiograms were
      rereviewed to detect additional PEs suggested by the iodine map. Consensus
      reviews were performed for examinations with PEs. The confidence interval of
      percentages was calculated by using the Clopper-Pearson method. Results On 147 of
      1144 (12.8%) CT angiograms, a total of 372 PEs were detected at initial review.
      After review of the DE CT iodine map, 27 additional PEs were found on 26 of 1144
      CT angiograms (2.3%; 95% confidence interval [CI]: 1.5%, 3.3%). Of the 27
      additional PEs, six (22.2%) were segmental, 21 (77.8%) were subsegmental, 24
      (88.9%) were occlusive, and three (11.1%) were nonocclusive. Eleven of 1144
      (1.0%; 95% CI: 0.5%, 1.7%) CT angiograms had a new diagnosis of PE after review
      of the DE CT iodine maps. Conclusion Dual-energy CT iodine maps show a small
      incremental benefit for the detection of occlusive segmental and subsegmental
      pulmonary emboli. (c) RSNA, 2018.

PMID- 30204076
TI  - Altered Nucleus Basalis Connectivity Predicts Treatment Response in Mild
      Cognitive Impairment.
AB  - Purpose To determine whether functional connectivity (FC) mapping of nucleus
      basalis of Meynert (NBM) cholinergic network (hereafter, NBM FC) could provide a
      biomarker of central cholinergic deficits with predictive potential for response
      to cholinesterase inhibitor (ChEI) treatment. Materials and Methods The
      Alzheimer's Disease Neuroimaging Initiative (ADNI) was approved by the
      institutional review boards of all participating sites. All participants and
      their representatives gave written informed consent prior to data collection. NBM
      FC was examined in 33 healthy control participants, 102 patients with mild
      cognitive impairment (MCI), and 33 patients with AD by using resting-state
      functional MRI data from the ADNI database. NBM FC was compared between groups
      before and after 6 months of ChEI treatment in MCI. Associations between baseline
      NBM FC and baseline cognitive performance as well as cognitive outcomes after
      treatment were investigated. Results Compared with the healthy control group, NBM
      FC was decreased in patients with untreated MCI and increased in patients with AD
      treated with ChEI (corrected P ? .05). Global cognition (Alzheimer's Disease
      Assessment Scale-Cognitive subscale score) was associated with NBM FC (r = 
      0.349; P ? .001). NBM FC was higher 6 months after ChEI compared with before ChEI
      in treated MCI (corrected P ? .05), but did not change at 6 months in patients
      with untreated MCI (corrected P ? .05). Baseline NBM FC in MCI strongly predicted
      cognitive outcomes 6 months after ChEI (R2 = 0.458; P = .001). Conclusion
      Functional dissociation of the nucleus basalis of Meynert from a cortical network
      may explain the cognitive deficits in dementia and allow for the selection of
      individuals who are more likely to respond to cholinesterase inhibitors at early
      disease stages. (c) RSNA, 2018 Online supplemental material is available for this
      article.

PMID- 30204079
TI  - Can Coregistered Photoacoustic Tomography and US Be Used in Screening for Ovarian
      Cancer?

PMID- 30204077
TI  - Observer Performance with Varying Radiation Dose and Reconstruction Methods for
      Detection of Hepatic Metastases.
AB  - Purpose To estimate the ability of lower dose levels and iterative reconstruction
      (IR) to display hepatic metastases that can be detected by radiologists.
      Materials and Methods Projection data from 83 contrast agent-enhanced CT
      examinations were collected. Metastases were defined by histopathologic analysis
      or progression and regression. Lower radiation dose configurations were
      reconstructed at five dose levels with filtered back projection (FBP) and IR
      (automatic exposure control settings: 80, 100, 120, 160, and 200 quality
      reference mAs [QRM]). Three abdominal radiologists circumscribed metastases,
      indicating confidence (confidence range, 0-100) and image quality. Noninferiority
      was assessed by using jackknife alternative free-response receiver operating
      characteristic (JAFROC) analysis (noninferiority limit, -0.10) and reader
      agreement rules, which required identification of metastases identified at
      routine dose, and no nonlesion localizations in patients negative for metastases,
      in 71 or more patient CT examinations (of 83), for each configuration. Results
      There were 123 hepatic metastases (mean size, 1.4 cm; median volume CT dose index
      and size-specific dose estimate, 11.0 and 13.4 mGy, respectively). By using
      JAFROC figure of merit, 100 QRM FBP did not meet noninferiority criteria and had
      estimated performance difference from routine dose of -0.08 (95% confidence
      interval: -0.11, -0.04). Preset reader agreement rules were not met for 100 QRM
      IR or 80 QRM IR, but were met for doses 120 QRM or higher (ie, size-specific dose
      estimate >= 8.0 mGy). IR improved image quality (P < .05) but not reader
      performance. Other than 160 QRM IR, lower dose levels were associated with
      reduced confidence in metastasis detection (P < .001). Conclusion For detection
      of hepatic metastases by using contrast-enhanced CT, dose levels that
      corresponded to 120 quality reference mAs (size-specific dose estimate, 8.0 mGy)
      and higher performed similarly to 200 quality reference mAs with filtered back
      projection. (c) RSNA, 2018 Online supplemental material is available for this
      article.

PMID- 30204078
TI  - Evaluation of Ovarian Cancer: Initial Application of Coregistered Photoacoustic
      Tomography and US.
AB  - Purpose To assess transvaginal coregistered photoacoustic tomography (PAT) and
      pulse-echo US for diagnosis of ovarian cancer based on functional parameters
      provided by PAT. Materials and Methods Between February 2017 and December 2017,
      26 ovarian masses from 16 participants were successfully imaged in vivo by
      multispectral photoacoustic imaging, including nine invasive epithelial ovarian
      cancers (six serous carcinomas and three endometroid adenocarcinomas), three
      other tumors (two borderline serous tumors and one sex cord-stromal tumor), and
      14 benign and normal (hereafter referred to as benign/normal) ovaries. The
      relative total hemoglobin concentration (rHbT) and mean oxygen saturation (sO2)
      shown at PAT were used to characterize the ovaries identified at US. Results The
      average rHbT was 1.9 times higher for invasive epithelial cancers than for the
      benign/normal ovaries (P = .01). Additionally, the rHbT distribution was
      extensive in invasive epithelial cancers, but was scattered in benign/normal
      ovaries. However, the rHbT of two borderline serous tumors and one stromal tumor
      was in the same range as that of benign/normal ovaries. The mean sO2 of invasive
      epithelial cancers, and of the borderline and stromal tumors, was 8.2% lower than
      that of benign/normal ovaries (P = .003). Discussion Invasive epithelial ovarian
      cancers showed higher and extensive tumor vascularity and lower oxygen saturation
      than benign and normal ovaries. Two borderline noninvasive serous and one stromal
      tumor showed low oxygen saturation compared with benign and normal ovaries.
      (c)RSNA, 2018 Online supplemental material is available for this article.

PMID- 30204080
TI  - ICTV Virus Taxonomy Profile: Fimoviridae.
AB  - Members of the family Fimoviridae, order Bunyavirales are plant viruses with
      segmented, linear, single-stranded, negative-sense RNA genomes. They are
      distantly related to orthotospoviruses and orthobunyaviruses of the families
      Tospoviridae and Peribunyaviridae, respectively. The family Fimoviridae includes
      the genus Emaravirus, which comprises several species with European mountain ash
      ringspot-associated emaravirus as the type species. Fimoviruses are transmitted
      to plants by eriophyid mite vectors and induce similar characteristic
      cytopathologies in their host plants, including the presence of double membrane
      bound bodies in the cytoplasm of the virus-infected cells. This is a summary of
      the International Committee on Taxonomy of Viruses (ICTV) Report on the taxonomy
      of the Fimoviridae, which is available at www.ictv.global/report/fimoviridae.

PMID- 30204075
TI  - Gadolinium Retention: A Research Roadmap from the 2018 NIH/ACR/RSNA Workshop on
      Gadolinium Chelates.
AB  - Gadolinium-based contrast agents (GBCAs) have revolutionized MRI, enabling
      physicians to obtain crucial life-saving medical information that often cannot be
      obtained with other imaging modalities. Since initial approval in 1988, over 450
      million intravenous GBCA doses have been administered worldwide, with an
      extremely favorable pharmacologic safety profile; however, recent information has
      raised new concerns over the safety of GBCAs. Mounting evidence has shown there
      is long-term retention of gadolinium in human tissues. Further, a small subset of
      patients have attributed a constellation of symptoms to GBCA exposure, although
      the association of these symptoms with GBCA administration or gadolinium
      retention has not been proven by scientific investigation. Despite evidence that
      macrocyclic GBCAs show less gadolinium retention than linear GBCAs, the safety
      implications of gadolinium retention are unknown. The mechanism and chemical
      forms of gadolinium retention, as well as the biologic activity and clinical
      importance of these retained gadolinium species, remain poorly understood and
      underscore the need for additional research. In February 2018, an international
      meeting was held in Bethesda, Md, at the National Institutes of Health to discuss
      the current literature and knowledge gaps about gadolinium retention, to
      prioritize future research initiatives to better understand this phenomenon, and
      to foster collaborative standardized studies. The greatest priorities are to
      determine (a) if gadolinium retention adversely affects the function of human
      tissues, (b) if retention is causally associated with short- or long-term
      clinical manifestations of disease, and (c) if vulnerable populations, such as
      children, are at greater risk for experiencing clinical disease. The purpose of
      the research roadmap is to highlight important information that is not known and
      to identify and prioritize needed research. (c)RSNA, 2018 Online supplemental
      material is available for this article .

PMID- 30204082
TI  - Tracing a protein's folding pathway over evolutionary time using ancestral
      sequence reconstruction and hydrogen exchange.
AB  - The conformations populated during protein folding have been studied for decades;
      yet, their evolutionary importance remains largely unexplored. Ancestral sequence
      reconstruction allows access to proteins across evolutionary time, and new
      methods such as pulsed-labeling hydrogen exchange coupled with mass spectrometry
      allow determination of folding intermediate structures at near amino-acid
      resolution. Here, we combine these techniques to monitor the folding of the
      ribonuclease H family along the evolutionary lineages of T. thermophilus and E.
      coli RNase H. All homologs and ancestral proteins studied populate a similar
      folding intermediate despite being separated by billions of years of evolution.
      Even though this conformation is conserved, the pathway leading to it has
      diverged over evolutionary time, and rational mutations can alter this
      trajectory. Our results demonstrate that evolutionary processes can affect the
      energy landscape to preserve or alter specific features of a protein's folding
      pathway.

PMID- 30204081
TI  - Oligodendrocyte-encoded Kir4.1 function is required for axonal integrity.
AB  - Glial support is critical for normal axon function and can become dysregulated in
      white matter (WM) disease. In humans, loss-of-function mutations of KCNJ10, which
      encodes the inward-rectifying potassium channel KIR4.1, causes seizures and
      progressive neurological decline. We investigated Kir4.1 functions in
      oligodendrocytes (OLs) during development, adulthood and after WM injury. We
      observed that Kir4.1 channels localized to perinodal areas and the inner myelin
      tongue, suggesting roles in juxta-axonal K+ removal. Conditional knockout (cKO)
      of OL-Kcnj10 resulted in late onset mitochondrial damage and axonal degeneration.
      This was accompanied by neuronal loss and neuro-axonal dysfunction in adult OL
      Kcnj10 cKO mice as shown by delayed visual evoked potentials, inner retinal
      thinning and progressive motor deficits. Axon pathologies in OL-Kcnj10 cKO were
      exacerbated after WM injury in the spinal cord. Our findings point towards a
      critical role of OL-Kir4.1 for long-term maintenance of axonal function and
      integrity during adulthood and after WM injury.

PMID- 30204086
TI  - DESARDA TECHNIQUE FOR INGUINAL HERNIA REPAIR.
AB  - Worldwide, more than 20 million patients undergo inguinal hernia repair annually.
      The problem of our age is to find an operation that is simple, does not require
      implantation of a foreign body like mesh and does not produce major complications
      during or after surgery. We represent 118 male patients who underwent
      hernioplasty by Desarda method between 2008 and 2017. 84 were elective and 34 -
      acute patients, respectively. Hernias in 26 cases were direct, 88 - indirect.
      Among elective cases 2 patients had bilateral hernia. 2 elective patients had
      recurrent hernia. There were 6 scrotal hernias, 13 - sliding hernia cases among
      elective patients. The age of patients was from 18 to 86 years. 33 patients were
      aged 70 and over. Among these 33 patients 12 had severe comorbidity of
      circulatory, respiratory systems and/or other diseases. Mean operating time was
      42.43+/-2.8 min. There were no intraoperative complications. Postoperative pain
      according to VAS (Mean +/- SD) on day 1 was 31,27+/-0.86. No patient had
      discomfort for more than 15 days after this repair. Among postoperative
      complications there were not any severe complications. No chronic pain, sensation
      of foreign body and no recurrence was observed. The mean hospital stay was 1.87+/
      0.78. According to our experience Desarda method seems to be an attractive
      alternative of other methods widely adopted today. Desarda repair has the
      potential to become the gold standard of hernia repair.

PMID- 30204083
TI  - Functionally asymmetric motor neurons contribute to coordinating locomotion of
      Caenorhabditis elegans.
AB  - Locomotion circuits developed in simple animals, and circuit motifs further
      evolved in higher animals. To understand locomotion circuit motifs, they must be
      characterized in many models. The nematode Caenorhabditis elegans possesses one
      of the best-studied circuits for undulatory movement. Yet, for 1/6th of the
      cholinergic motor neurons (MNs), the AS MNs, functional information is
      unavailable. Ventral nerve cord (VNC) MNs coordinate undulations, in small
      circuits of complementary neurons innervating opposing muscles. AS MNs differ, as
      they innervate muscles and other MNs asymmetrically, without complementary
      partners. We characterized AS MNs by optogenetic, behavioral and imaging
      analyses. They generate asymmetric muscle activation, enabling navigation, and
      contribute to coordination of dorso-ventral undulation as well as anterio
      posterior bending wave propagation. AS MN activity correlated with forward and
      backward locomotion, and they functionally connect to premotor interneurons
      (PINs) for both locomotion regimes. Electrical feedback from AS MNs via gap
      junctions may affect only backward PINs.

PMID- 30204087
TI  - [SURGICAL TREATMENT OF PARKINSON'S DISEASE WITH LEVODOPA-INDUCED MOVEMENT
      DISTURBANCES].
AB  - Aim - to evaluate the efficacy of stereotactic pallidotomy and bilateral deep
      brain stimulation (DBS) of subthalamic nuclei (STN) in patients with Parkinson
      disease with motor fluctuations and levodopa-induced dyskinesias. 36 patients
      (age range 31-73 years (mean age 56.2+/-3.2 years) were enrolled in study. Mean
      duration of PD was 9.8+/-1.1years. All patients used levodopa-drugs, mean
      levodopa dose was 1075+/-304.1 mg/day. Mean duration of motor fluctuations and
      levodopa-induced dyskinesias before surgery was 2,18+/-0,8 years. Patients = were
      divided into 2 groups - 22 patients underwent stereotactic unilateral pallidotomy
      and 14 patients underwent bilateral DBS (STN target). Neurological and
      psychological status assessed before and after treatment by: UPDRS II, Hoehn and
      Yahr scale, Schwab and England scale, MMSE, Beck's Depression Inventory, Hamilton
      Depression Rating Scale, Hamilton Anxiety Rating Scale and PDQ-39. Surgery
      performed on CRW stereotactic system. Postoperative follow-upranged from 1 to 8.5
      years (mean 4.1+/-1.1 years). Regression of tremor, rigidity, bradykinesia and
      levodopa-induced dyskinesia observed in most patients after stereotactic
      interventions. The best results were achieved in patients who underwent DBS. In
      this group UPDRS II score improved by 74% in ON period and by 63% in OFF period.
      After pallidotomy UPDRS II score improved by 55% in ON period and by 47% in OFF
      period. Levodopa-induced dyskinesia stopped in 21 from 22 (95.5%) patients who
      had it before surgery after unilateral pallidotomy and in 11 from 12 (91.7%)
      patients after DBS. Surgical complications occurred in 3 (13.6%) case after
      pallidotomy, which induced transient neurological deficit. Our results
      demonstrate that both stereotactic interventions - pallidotomy and DBS are
      effective and safe methods of treatment of PD with levodopa-induced dyskinesias
      and motor fluctuations. Both surgeries improve overall motor function, increased
      patient's mobility and improve quality of life.

PMID- 30204088
TI  - [CERVICAL CANCER REHABILITATION: A PROSPECTIVE STUDY].
AB  - Aim - to evaluate the rehabilitation program impact on the quality of life of
      oncogynecological patients and to introduce this approach in clinical practice.
      The study included93 reproductive-aged women, who underwent the cervical cancer
      treatment. Patients were divided into two groups: the experimental group, which
      received rehabilitation, and the control group. The thrombotic complications
      risk, lymphatic system condition, cognitive functions and anxiety level were
      assessed in all patients using special questionnaires, physical examination, and
      laboratory assessment. The lower limbs lymphedema was observed in 19.1% of cases
      in the control group and in 2.1% in the experimental group (p <0.05). According
      to the Moka test data, cognitive impairment level at the end of the study was
      24.02 (17-30, CI: = 22.5-25.54) in the control group and 26.85 (19-30, CI: = 26.0
      - 27.64) in the experimental group (p <0.05). The cognitive impairment subjective
      signs were significantly higher in the control group (p <0.05) as well. The
      anxiety level at the end of the study was 7.022 (1-19, CI: = 5.91-8.13) in the
      experimental group and 11.02 (4-22, CI: = 9.83-12.22) in the control group (p
      <0.05). At the end of the study, the following depression levels were obtained:
      12.43 (5 - 21; CI: = 11.23 - 13.64) and 7.69 (1 -14; CI: = 6.77 - 8.62) in the
      control and the experimental group respectively (p <0.05). At the end of the
      study, deep vein thrombosis was observed in 21 patients in the control group
      (44.7%) and 7 patients in the experimental group (15.22%) (p <0.05). One patient
      from the control group had PATE. According to EORTC QLQ-C30, the quality of life
      and socialization level was significantly higher in the experimental group, while
      fatigue level was lower. At the end of the study, 36.2% and 76.0% of patients in
      the control and the experimental group respectively were employed. The
      rehabilitation program improves the emotional and cognitive functioning, induced
      menopause associated somatic disorders, quality of life, and work capacity.

PMID- 30204085
TI  - Identification of cryptic subunits from an apicomplexan ATP synthase.
AB  - The mitochondrial ATP synthase is a macromolecular motor that uses the proton
      gradient to generate ATP. Proper ATP synthase function requires a stator linking
      the catalytic and rotary portions of the complex. However, sequence-based
      searches fail to identify genes encoding stator subunits in apicomplexan
      parasites like Toxoplasma gondii or the related organisms that cause malaria.
      Here, we identify 11 previously unknown subunits from the Toxoplasma ATP
      synthase, which lack homologs outside the phylum. Modeling suggests that two of
      them, ICAP2 and ICAP18, are distantly related to mammalian stator subunits. Our
      analysis shows that both proteins form part of the ATP synthase complex.
      Depletion of ICAP2 leads to aberrant mitochondrial morphology, decreased oxygen
      consumption, and disassembly of the complex, consistent with its role as an
      essential component of the Toxoplasma ATP synthase. Our findings highlight
      divergent features of the central metabolic machinery in apicomplexans, which may
      reveal new therapeutic opportunities.

PMID- 30204089
TI  - CURRENT CONDITION AND CHALLENGES IN TREATMENT OF NON-HEALING WOUND AFTER
      RADIATION THERAPY (REVIEW).
AB  - Radiotherapy is a common cancer treatment, but often together with tumor cells,
      the surrounding normal tissues are damaged as well, which leads to the
      complications such as skin atrophy, soft tissue fibrosis, desquamation,
      epithelial ulceration which leads to poor healing of wounds. In this review, our
      main attention will be paid to the treatment of non-healing wound after radiation
      therapy. Irradiated wounds are often resistant to conventional treatment
      modalities and may often require surgical reconstructive intervention. The
      reconstructive options usually include skin grafts, local and regional flaps.
      Local flaps may be unreliable, since in some of the cases they are affected by
      irradiation. However, the complication rate with regional flaps is just as high
      as that with local flaps, and is not significantly different when analyzed
      according to the type of reconstructive procedure performed. In addition, such
      wounds affect not only the physical, but also the mental health of patients and
      their productivity. Therefore, non-healing wounds represent a significant problem
      for patients and remain a major challenge in modern medicine. Recently, for the
      healing of non-healing wound, several novel approaches have been proposed such as
      using the bone marrow stem cells (BMSC), biologically active dressings,
      bioengineered skin equivalents and others. Of special interest are bioactive
      membrane consisting of decellularized human amniotic membrane and BMSC paracrine
      factors, which may be effectively used for the treatment of non-healing wounds
      that have developed following the radiotherapy. Despite the positive results
      achieved in a number of cases, it is early to state that the all of the above
      methods is an ideal for the treatment of non-healing wounds, since it requires
      additional experimental and clinical studies for ascertaining positive and
      negative features.

PMID- 30204084
TI  - Elucidating the mitochondrial proteome of Toxoplasma gondii reveals the presence
      of a divergent cytochrome c oxidase.
AB  - The mitochondrion of apicomplexan parasites is critical for parasite survival,
      although the full complement of proteins that localize to this organelle has not
      been defined. Here we undertake two independent approaches to elucidate the
      mitochondrial proteome of the apicomplexan Toxoplasma gondii. We identify
      approximately 400 mitochondrial proteins, many of which lack homologs in the
      animals that these parasites infect, and most of which are important for parasite
      growth. We demonstrate that one such protein, termed TgApiCox25, is an important
      component of the parasite cytochrome c oxidase (COX) complex. We identify
      numerous other apicomplexan-specific components of COX, and conclude that
      apicomplexan COX, and apicomplexan mitochondria more generally, differ
      substantially in their protein composition from the hosts they infect. Our study
      highlights the diversity that exists in mitochondrial proteomes across the
      eukaryotic domain of life, and provides a foundation for defining unique aspects
      of mitochondrial biology in an important phylum of parasites.

PMID- 30204090
TI  - [PECULIARITIES OF TREATMENT OF DISTRIBUTED FORMS OF THORACIC PART OF ESOPHAGEAL
      CANCER].
AB  - The aim of this study is to evaluate the methods of treatment of thoracic part of
      esophageal cancer and to predict the results of treatment depending on the
      factors of the prognosis. The results of treatment of 366 patients with cancer of
      the thoracic part of esophagus for 10 years (2007-2016) on the basis of the
      department of thoracic oncology of the Karaganda oncological dispensary were
      studied. The overall five-year survival rate, regardless of the method of
      treatment, was only 8.72% (28 of 321), and in the 6-10 year period 8.41% (27 of
      321) lived, p <0.05. Analysis of the overall survival of patients with cancer of
      the thoracic part of esophagus showed that the method of treatment does not have
      a significant effect on life expectancy. A multivariate analysis of 19 grades
      that affect the prognosis of the disease was carried out. Radical type of
      treatment of the middle and lower thoracic esophagus is surgical, in which the
      median of cumulative survival is 19 months. Traditional radiotherapy should be
      used in a limited way, as it is palliative, with a median survival of no more
      than 9 months. The leading factor in the prognosis for thoracic part of
      esophageal cancer is the presence of regional metastases, on which the choice of
      method of treatment depends.

PMID- 30204091
TI  - CONDITION OF NON-SPECIFIC RESISTANCE OF ORAL MUCOUS MEMBRANE IN CHILDREN WITH
      VIRAL INFLUENZA STOMATITIS IN THE CONCEPT OF MALT-SYSTEM.
AB  - Mucous membrane of oral cavity is the first open section of the digestive system
      and respiratory tract, first mechanical barrier from penetration of infectious
      diseases pathogens and antigens, is always exposed to constant contamination and
      is forming the microecology of oral cavity and lower sections of digestive tract.
      Aim - to analyze the state of colonization resistance of the mucosa,
      microbiocenosis of the oral cavity, physico-chemical characteristics of the oral
      fluid in children with influenza stomatitis. Clinical and laboratory examination
      of 384 children with acute respiratory viral infections was made using clinical,
      microbiological, cytological methods of investigation. The conducted study
      allowed to distinguish 3 types of cytograms, each of which corresponds to the
      severity of disease. We found the relationship between the nature of microflora
      taken from the oral mucous membrane and the severity of acute respiratory viral
      infections, which shows signs of III-IV degree dysbiosis in patients with severe
      form of the disease. We diagnosed decrease of the stability indicators and the
      interval of pH waves indicating a decrease in the level of functional reserves of
      the oral cavity. Detected changes in the colonization resistance of oral mucous
      membrane and the microbiocenosis structure of oral cavity, acid-salt metabolism
      of the oral liquid in children with influenza stomatitis are the indicators of
      non-specific resistance of oral cavity mucous membrane.

PMID- 30204092
TI  - [EVALUATION OF THE COMPARATIVE TOXICITY OF VARIOUS MATERIALS FOR DENTAL
      PROSTHETICS ON CELL CULTURE MODELS].
AB  - Difficulties in repairing the defects of the teeth are related with allergic
      inflammatory, traumatic and dystrophic complications arising from the interaction
      of the foreign body with the mucous tissues of the oral cavity after the
      patient's prosthesis is established. The aim of our study was to establish the
      toxic pro-inflammatory activity of materials used for the manufacturing of bases
      of removable dentures - plastics based on polymethylmethacrylate prosthetic
      complexes Prothyl Hot, Ftorax and Perflex Flexi Nylon on the model of human
      leukemia transformed T cells (Jurkat cells) and MDCK cells. For the cells
      simulation Jurkat and MDCK cells was incubated with the components of prosthetic
      materials, Prothyl Hot, Ftorax and Perflex Flexi Nylon/ Prosthetic materials were
      added to the incubation medium at the doses used in practice (calculated at 106
      cells); duration of incubation was 24 hours. A comparative assessment of the
      toxicity of prosthetic materials was determined by the MTT test (activity of
      mitochondrial dehydrogenases). Statistical analysis was carried out using the
      package (SPSS version 11.0). The statistical reliability of the difference
      between the indices was evaluated by the Student t test (the P <0.05 level was
      considered reliable). The results of the conducted studies testify to the absence
      of toxicity of the complexes Prothyl Hot, Ftorax and Perflex Flexi Nylon, used as
      a basis of circuit prostheses, on intact Jurkat and MDCK cells, as evidenced by
      the stability of their mitochondrial dehydrogenases. Based on the analysis of the
      conducted studies, it can be concluded, that as Jurkat and MDCK cells are used as
      models of immune and epithelial cells, the materials used for manufacturing of
      removable prostheses, the polymethylmethacrylate-based plastics (Prothyl Hot and
      Ftorax) and elastic thermoplastic polymer material Perflex Flexi Nylon, are not
      toxic. Studied materials, with the high probability, are not capable to cause
      massive death of immune cells, development of allergic or inflammatory damages,
      which in turn can stat cause the development of stomatitis and gingivitis, the
      destruction of the paradental tissue.

PMID- 30204093
TI  - ANALYSIS OF DIAGNOSTICS AND NEWEST PATHOGENESIS ASPECTS OF TEMPOROMANDIBULAR
      DYSFUNCTION (REVIEW).
AB  - The research was predisposed for a progressing increase in incidence of the
      temporomandibular joint dysfunction, low effectiveness of traditional treatment
      as well as the necessity of implementation of high-effective etiopathogenetic
      therapy methods. The necessity of systematizing diagnostics and treatment
      planning is evident, considering the cause-effect mechanisms of the disease
      initiation and complex individual approach, required for improving the
      effectiveness of prevention and pathogenetic therapy in early rehabilitation of
      the patients with the temporomandibular dysfunction, The visualization model will
      provide for planning certain treatment stages using a virtual system,
      synchronizing and combining them with the modern methods of the prosthetic
      construction fabrication, which will represent a new quality stage of
      stomatological treatment. The chosen theme is not only of multidisciplinary
      medical importance, but of the social one as well. The wide coverage of the theme
      in stomatological sources evidences about urgency of searching for the new
      diagnostic sources and treatment methods and proves actuality of the topic. The
      article presents urgent aspects of the temporomandibular dysfunction development
      pathogenetic mechanisms, depicts new methods of diagnostics and early clinical
      manifestations, reviewed by the Ukrainian and foreign scientists over the
      previous 10 years.

PMID- 30204094
TI  - FEATURES OF HEMODYNAMICS IN VERTEBROBASILAR ARTERIAL SYSTEM IN YOUNG PEOPLE,
      DEPENDING ON BIOMECHANICAL DISORDERS OF THE MUSCULOSKELETAL SYSTEM.
AB  - In order to study the features of hemodynamics in the vertebral artery (VA),
      depending on the biomechanical disorders of the cervical spine (CS) and the
      musculoskeletal system as a whole 105 patients (53 females and 52 males, mean age
      - 38+/-5,9 years) having signs of the Vertebrobasilar insufficiency on the
      background of biomechanical disorders of the CS and the locomotor system as a
      whole were examined. The control group included 50 practically healthy persons
      (25 females and 25 males, mean age - 37+/-5,6 years). Physical examination
      included a clinical-neurological, vertebro-neurological examination (visual
      assessment of violations of statics and dynamics of the musculoskeletal system,
      measuring the craniovertebral angle (CVA) using a photogrammetric method, manual
      diagnostics for the detection of muscular-tonic syndromes and musculoskeletal
      dysfunction) and Doppler ultrasound of extra- and intracranial segments of VA. It
      was revealed the relationship between the violation of hemodynamics in
      vertebrobasilar system and pathobiomechanical changes of the musculoskeletal
      system in patients of young age. The leading pathogenetic role in the onset of
      hemodynamic disorders in VA belongs to a non-optimal static stereotype in the
      cervical region in the form of displacement of the regional center of gravity
      forward with the formation of a forward head position. It was revealed a positive
      correlation between the value of CVA and the degree of mobility of the
      craniovertebral transition by A. Stoddart (r = +0.79, p <0.05) and also - a
      negative correlation between CVA value and the level of blood flow reduction in
      VA during functional rotational tests (r=-0,69, p<0,05).

PMID- 30204095
TI  - [MANAGEMENT OF PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS IN THE PREPREGNANCY AND
      ANTENATAL PERIODS: CHALLENGES AND SOLUTIONS (REVIEW)].
AB  - Systemic lupus erythematosus (SLE) is a rare, multi-systemic chronic autoimmune
      disease characterized by hyperproduction of organ-specific autoantibodies to
      various components of the cell nucleus with the development of immuno
      inflammatory damage of tissues and internal organs, predominantly affecting
      women, particularly those of childbearing age. Hence future pregnancy is one of
      the key issues of the modern rheumatology. The management of the SLE patient
      should include an effective risk assessment of the future pregnancy and
      stratification followed by an individualized antenatal care program. Timely
      detection of exacerbations and complications (medical and/or obstetric) is the
      leading prerogative of pregnancy management in SLE patients with the involvement
      of relevant practitioners. The purpose of our study was a review of literature
      related to the patients with SLE management by rheumatologists, obstetrician
      gynecologists in prepregnancy and antenatal periods. The systematization of
      approaches to the management of SLE patients during these periods has been
      carried out, allowing practitioners to effectively assign appropriate diagnostic
      manipulations and timely safe treatment.

PMID- 30204096
TI  - [ANALYSIS OF COGNITIVE DISORDERS WITH DIFFERENT CLINICAL FORMS OF PARKINSON'S
      DISEASE].
AB  - The purpose of this study is to assess the dynamics of cognitive impairment in
      patients with Parkinson's disease during the first 2 years of the disease, to
      study the peculiarities of cognitive impairment in patients with Parkinson's
      disease with different clinical forms. The study included 54 patients, 30 men and
      18 women. After a year, 51 patients were re-admitted, in 2 years - 48 patients (6
      patients were not included in the end). Average age at the beginning of the study
      was 65.6 +/-3.7 years. The duration of the disease ranged from 2 to 8 years and
      averaged 5.9 +/-4.2 years, the mean age at the onset of the disease was 58.4+/
      4.3 years. The digital data was processed by a variational-statistical method.
      Student's t-test was used. Correlation analysis is performed by the method of
      Spearman's rank correlation. The diagnosis was established according to the
      criteria developed by Hughes et al. All patients underwent CT or MRI examination.
      Patients in clinical forms were divided into 3 groups: I group - rigid
      bradykinetic form - 13 patients; Group II - the mixed (tremor-rigid) form 24
      patient; Group III - the trembling form - 11 patients. The mental sphere of the
      patients was studied on a psychomotor scale at the beginning of the study, after
      1 and 2 years, the Blessed information-Memory-Concentration (BIMC) test was used.
      Studies have shown that with Parkinson's disease, along with motor impairments,
      mental sphere disorders occur, although not in all cases. Approximately in 25% of
      cases mental disorders are not detected. Clinically significant worsening of
      cognitive functions during 2 years is observed in 20.83% of patients. A vivid
      correlation between the mental deficit and clinical forms of the disease was not
      found (p<0.5).

PMID- 30204097
TI  - THE PREVALENCE OF HIRSUTISM AND ETHNICAL PECULIARITIES OF HAIR DISTRIBUTION IN
      GEORGIAN ADOLESCENT POPULATION IN TBILISI.
AB  - Objective - the purpose of the study is evaluation of the Hirsutism prevalence
      and ethnical peculiarities of the hair distribution in Georgian female
      adolescents of Tbilisi, Georgia. 2592 randomly selected female adolescents of
      Tbilisi were included in the study. They completed standard questionnaires
      consisted of questions about the existence of hirsutism and its locations. For
      clinical assessment 2 groups were selected from them: group 1 - 117 adolescents
      with hirsutism and 178 without it. For clinical evaluation of hirsutism modified
      Ferriman-Gallwey score was used. Based on the self-estimation the hirsutism
      prevalence was 26.62% (690 out of 2592), while clinically established prevalence
      of hirsutism was 20.61%. The most prevalent areas of hair distribution by self
      estimation were the face and the abdomen. Clinical assessment of patients with
      hirsutism showed that mean value of Ferriman-Gallwey Score was 12.87+/-5.94. Hair
      distribution by clinical assessment was most significantly observed in the lower
      abdomen (78.33%), upper lip (76.67%) and chest (68.33%). This is the first study
      of hirsutism prevalence in ethnically Georgian adolescent female population. The
      study has shown that the value of prevalence by self-estimation exceeds analogous
      value established clinically, and the sites with hair excess are lower abdomen,
      upper lip and the chest.

PMID- 30204098
TI  - IMPACT OF SOCIOECONOMIC STATUS ON CARDIOVASCULAR RISK IN GEORGIAN POPULATION.
AB  - Cardiovascular diseases (CVD) continue to be the leading cause of death and
      disability worldwide, representing 30% of all death. In Georgia 36% of all death
      caused by ischemic heart disease and 23% caused by stroke. There is a limited
      data on association between socioeconomic status (SES) and CVD risk in Georgia.
      Our study aims at assessing association between SES and CVD risk factors in a
      cohort of adult Georgians. A cross-sectional study was conducted in the region of
      Western Georgia between June 2007 - June 2008. 1196 individuals aged 40-70 years
      were enrolled in the study. To assess SES we collected information about
      education, income, ownership of a private transport, and employment. CVD risk was
      assessed by the WHO/ISH risk classification scale. In addition, anthropometric
      measurements were conducted in each study participant. Low education level
      (adjusted odds ratio (aOR) 2.85; 95% confidence interval (CI), 1.57-5.17),
      obesity (aOR 2.13, 95% CI 1.16 -3.92) and abdominal obesity (aOR 2.21, 95% CI
      1.26 -3.87) were statically significantly associated with more than 10% 10 year
      risk of a fatal or non-fatal cardiovascular event. Lower education level (not
      finished high school -aOR 2.21 95% CI 1.44 - 3.38, undergraduate - aOR 1.52, 95%
      CI 1.12 - 2,05), income 120 USD or more (aOR 0.73, 95% CI 0.54 -1.00), overweight
      (aOR 1.68, 95% CI 1.07 - 2.63), obesity (aOR 1.58, 95% CI 1.04 - 2.41), and
      abdominal obesity (aOR 1.43, 95% CI 1.01 - 2.03) were found to be statistically
      significant predictors of CVD in our study population. We found that education
      level, income, body mass index and waist to hip ratio are CVD risk factors.
      Public health authorities, as well as clinicians should consider this finding in
      primary and secondary prevention and organize multidisciplinary teams to address
      those risk factors.

PMID- 30204099
TI  - INFLUENCE OF LEFT VENTRICULAR DIASTOLIC DYSFUNCTION AND HEART DYSSYNCHRONY ON THE
      COURSE OF ARTERIAL HYPERTENSION WITH COMORBID PATHOLOGY.
AB  - The aim of the study is determination of the role of left ventricular dysfunction
      and heart dyssynchrony in the disease's course and prognosis in patients with
      arterial hypertension and diabetes mellitus type 2 (DM2T) and obesity. A
      retrospective analysis of clinical and special exam results was carried out in
      different groups: 1st group (n = 49), is characterized by worsening course (WC)
      of the disease, that was estimated 6 months after the beginning of the study; 2nd
      group (n = 86) without worsening of disease's course. The criterion of worsening
      course in patients was exaggeration of target-organ damage. The diastolic
      function of the myocardial infarction was assessed by recording the Doppler
      transmitral diastolic flow. Heart dyssynchrony was determined in the M-mode and
      pulse-wave/continuous-wave Doppler (PW/CW). The diastolic function of the LV has
      significant association with the progression of hypertension. The results of the
      study show that both slowdown and acceleration of the maximum early ventricular
      filling velocity (E) were indicative for patients with progression of the
      disease, and moderate E values was significantly more frequent in the group
      without progression of the disease. The maximum late ventricular filling velocity
      parameter (A) (acceleration) was significantly more common in the 1st group (p <=
      0.001), and the moderate value of A index (<= 0.71 msec.) was diagnosed more
      often in the group without progression. Furthermore, the decline of LV relaxation
      velocity (E/A <= 1.0) was detected in the group with disease's progression
      significantly more often (p <= 0.001) compared with the 2nd group, therefore we
      suppose that it has a pathogenic significance. In addition, a decrease in
      diastolic filling time <= 200 ms, as well as a slowing of the time of isovolumic
      relaxation of the LV (IVRT >= 201 ms) both revealed a pathogenic significance (p
      <= 0,001), which were diagnosed more often (p <= 0.001) in the group with
      disease's progression. Violation of diastolic function is a significant factor of
      the hypertension progression in patients with T2DM. The presence of LV
      dyssynchrony that is associated with the LV hypertrophy is a great predictor for
      the worsening course in hypertensive patients with T2DM and obesity.

PMID- 30204100
TI  - GENDER SPECIFIC DIFFERENCES IN REPORTING DEPRESSIVE SYMPTOMS AMONG PATIENTS
      HOSPITALIZED WITH ACUTE CORONARY SYNDROME.
AB  - In patients with acute coronary syndrome (ACS) low level of depressive symptoms
      is associated with coronary event recurrence and morbidity. Large epidemiological
      trials revealed that there is a disparity between males and females in their
      reports of different somatic depressive symptoms. The aim of our study was to
      identify gender differences in reporting depressive symptoms in patients with
      acute coronary events. Depreesion screening using BDI questionnaire was performed
      in patients with ACS in Emergency Cardiology center, Tbilisi, Georgia. The total
      number of participants was 84. Patients' data were collected from hospital
      records. Descriptive statistical tests were used for the calculation of
      frequencies, means and standard deviations. Chi-square test was applied for
      categorical variables in order to establish difference between groups. The
      Independent t-test was used to compare means for numerical variables. The mean
      age for both genders was 59.2 (10.2) years. Classic coronary risk factors were
      more prevalent in men than in women. However, women, compared to men have a
      greater number of cognitive as well as somatic depressive symptoms. Women
      hospitalized with an acute coronary syndrome reported greater number of
      depressive symptoms compared to men. Early detection of depressive symptoms will
      help healthcare providers reduce risks and improve outcome of ACS.

PMID- 30204101
TI  - FACTORS AFFECTING THE FATAL OUTCOME IN HIV-INFECTED PATIENTS WITH ENCEPHALITIS.
AB  - Despite the successful use of ART up to 40-70% of HIV(+) individuals have
      neurologic complications caused both by the HIV itself and by the reactivation of
      OIs on the background of severe immunodeficiency. Nowadays, there are no
      universally recognized criteria that allow predicting the outcome of encephalitis
      caused by OIs in this category of patients. The aim of our study was to assess
      factors affecting the fatal outcome in HIV(+) patients with CNS involvement.
      Retrospectively we selected 53 HIV(+) patients with confirmed encephalitis due to
      OIs. Depending on the outcome of the disease, patients were divided into groups:
      non-survivors (n=22) and survivors (n=31), after compared their clinical
      manifestation, history of the disease and life, CSF results in the first days of
      admission. It has been established that the factors affecting the fatal outcome
      in HIV(+) patients with encephalitis are: the severity of the patient's condition
      upon admission, acuteness of the onset of the disease, the severity of neurologic
      symptoms, the degree of co-morbidity, the level of immunosuppression and viral
      load, absence of ART.

PMID- 30204102
TI  - INVESTIGATION OF PROTECTIVE EFFECTS OF SYNBIOTICS ON ALLERGOPATHY FORMATION.
AB  - A strategic direction of modern medicine in combating allergy is the search for
      new methods of primary prophylaxis, among which a key role may belong to
      normalization of the human body microflora. The aim of the research was to study
      the influence of synbiotics on bacteriological and immune indices in premature
      infants evaluating their preventive role in allergopathy formation. During
      prospective cohort investigation, 88 babies from one to four months of age, born
      on the 27th to 37th week of gestation to healthy mothers and women with
      allergopathy, were examined. Routine laboratory, bacteriological and instrumental
      investigations were performed. Measuring total serum IgE, cytokines IL-5, IL-10
      and TNF-alpha in coprofiltrates was performed by means of immunoenzymatic assay.
      The activity of histaminase was detected by means of "Histamine 50-Skin-Prick
      Test". All examined patients were divided into four groups, depend on parents's
      atopic disease and prescribing synbiotics. For month, children from the first and
      the third groups were administered a commercial synbiotic - nutritional
      supplement with probiotics and fructooligosaccharides in the dose: one billion
      viable microencapsulated bacteria Lactobacillus rhamnosus GG in combination with
      fructooligosaccharides. Children from the second and the fourth groups were not
      administered synbiotic. Control of indices was conducted after 4 weeks. On
      bacteriological analysis of feces, the number of lacto- and bifidobacteria
      increased by 30% in children from the first and the third groups. Indices of
      total serum IgE were within age norm both before intake of synbiotic (1-2 groups)
      and after treatment. A reliable (p<=0.01) reduction of TNF-alpha and increase in
      IL-10 was revealed in coprofiltrates of children, who received synbiotic Preema
      sachet. Inclusion of synbiotic, which contains one billion viable
      microencapsulated bacteria Lactobacillus rhamnosus GG in combination with
      fructooligosaccharides to complex therapy of premature children results in
      regulation of cytokine balance with the tendency to reduction of an inflammatory
      process and has a preventive effect concerning allergopathy formation.

PMID- 30204103
TI  - CHROMOSOMAL INSTABILITY AS A CYTOGENETIC MARKER IN CHILDREN WITH VARYING DEGREES
      OF CONTROL OF ASTHMA.
AB  - The aim of investigation was to learn cytogenetic karyotype characteristics of
      children with asthma, with varying degrees of control in order to find markers of
      disease severity. The study involved 82 children aged 6 to 18 years, patients
      with asthma who were treated in Allergic Department of Regional Pediatric
      Hospital of Ivano-Frankivsk. Regarding the level of controlled asthma as a result
      of the application of test control asthma (GINA, 2011) children were distributed
      as follows: - 22 (30.6%) with controlled (CBA), 24 (33.3%) - is partly controlled
      (PCBA) 26 (36.1%) - with uncontrolled asthma (NCBA). The control group children
      were selected by random sampling, living in different parts of the Ivano
      Frankivsk region (10 persons). Research of cytogenetic features of the karyotype
      in children with bronchial asthma was conducted by studying specimens of
      prometaphase chromosomes of peripheral blood lymphocytes. We analyzed
      associations of acrocentral number of chromosomes, karyotype features. The study
      involved 82 children aged 6 to 18 years with asthma of varying degrees of its
      control over the outcome of asthma control test. Children with uncontrolled
      asthma received significantly higher rate of chromosome acrocentral associations
      13-15 (DD), 21-22 (GG) and 13-15 - 21-22 (DG). In patients with asthma we
      observed a lower mitotic activity compared with that in healthy ones (PN <0.05),
      and with a lower degree of controllability it decreased. Recognition of the
      genetic mechanisms of asthma leads to a new understanding of the genesis of the
      disease and can move forward in developing methods of treatment and prevention.

PMID- 30204104
TI  - BIOMARKERS OF RENAL INJURY RISK IN CHILDREN WITH PYELONEPHRITIS.
AB  - The most common cause of fever in case of anomalies of the urinary system is
      pyelonephritis (PN). Despite the fact that an intensive search for informative
      clinical and laboratory markers of PN in children is being conducted in recent
      years, this problem remains unresolved. Objective - to examine the content of
      organ-specific enzymes (neutral alpha-glucosidase (NAG), L-alanine aminopeptidase
      (AAP), gamma-glutamyltranspeptidase (GGTP) in urine and galectin 3 (Gal -3), C
      reactive protein (CPR) in blood serum. A prospective, comprehensive clinical and
      laboratory-instrumental examination was performed in 75 children under the age of
      1. The activity of organ-specific enzymes (NAG, AAP, GGTP) in urine and CPR, Gal
      3 in the serum of blood were estimated as markers of proximal tubules' damage.
      The majority (62.99 +/- 5.33%) of hospitalized children with febrile temperature
      and urine changes were diagnosed with PN, which often arose with underlying
      congenital malformations of the urinary tract. Among children with PN underlaying
      with VUR, the II and III grades of activity were significantly more frequent. An
      increase of the level of the enzymes in the urine is observed in the active phase
      of PN, which correlated with the level of leukocyturia and the level of CRP.
      During the inactive phase of PN with VUR, the level of enzymes was also higher
      than the one in children with PN without VUR. High values of Gal-3 were detected
      in case of underlying VUR, which increased together with increased activity and
      duration of the inflammatory process in kidneys and correlated with the level of
      CRP. The Gal-3 can be used for an early diagnosis of fibrotic changes of the
      renal parenchyma in adolescent children with PN and underlying VUR.

PMID- 30204105
TI  - ASTHMA PREDICTIVE INDEX AND NITRIC OXIDE PROGNOSTIC VALUE IN YOUNG CHILDREN WITH
      RECURRENT WHEEZING.
AB  - The study was aiming at investigation of Asthma Predictive Index (API) and
      predictive value of quantitative changes in nitric/nitrogen oxide (NO) in
      children with recurrent wheezing of different phenotypes. An observing cross
      sectional clinical study where 120 patients 5 to 7 years of ages with wheezing
      syndrome were involved has been conducted. In the group of patients with
      multifactorial wheezing, 77%-positive results revealed in 65% of patients
      indicated to high probability of asthma formation. 59%-positive response to the
      API index prevailed in patients with episodic wheezing (28%). 77%-positive
      response sensitivity was 81% and specificity -93%, respectively. The increase in
      NO concentration (27.8+/-0.71) was fixed in 27.5% of patients with multifactorial
      wheezing, especially at 77% positive response to the API index. Measurement of
      API index and NO levels at early ages to reveal the contingent with high
      probability of asthma formation, especially in young children with multifactorial
      wheezing is of great importance.

PMID- 30204106
TI  - [ANALYSIS OF SOCIO-DEMOGRAPHIC FACTORS OF THE RISK OF BIRTH OF CHILDREN IS
      PREMATUREA IN REPUBLIC OF KAZAKHSTAN].
AB  - Aim of the study was the analysis of risk factors for the birth of premature
      infants in the city of Semey, Kazakhstan. We conducted a retrospective cohort
      study of maternal risk factors for the birth of children prematurely. Prematurely
      born are children born alive at the time of 37 full weeks of pregnancy. The study
      included live births born between 2012 and 2015 in the Perinatal Center of the
      City of Semey. We analyzed the katras of hospitalized sick mothers and their
      children. A total of 722 children were included in the study, of which 358 were
      premature babies and 364 full-term infants. Statistical processing of data was
      performed using IBM SPSS 20. With each subsequent pregnancy, the mother has a 1.2
      fold increase in the chances of having a baby prematurely (p=0.022). With each
      subsequent birth, the chances of having a baby increase prematurely 0.7 times
      (p=0.04). An increase in the age of menarche for 1 year increases the chances of
      having a baby prematurely 0.9 times (p=0.027). The male gender of the baby is
      also prematurely at risk (p=0.001). Premature birth is a multifactorial process
      we have found out that the frequency of childbirth and pregnancy, as well as the
      sex of the child and the age of the mother's menarche are factors of the child's
      birth prematurely. In order to prevent the birth of children, it is premature to
      conduct educational work with girls and women of childbearing age.

PMID- 30204107
TI  - POSSIBLE IMPLEMENTATION OF GABAERGIC AND GLUTAMATERGIC SYSTEMS IN REALIZATION OF
      ANTIEPILEPTIC EFFECTS OF ACOUSTIC RANGE ELECTRO - MAGNETIC FIELDS.
AB  - Seizure is a clinical manifestation of a hyperexcitable neuronal network, in
      which, the electrical balance underlying the normal neuronal activity is altered
      pathologically-excitation (Glutamatergic activity) predominates over inhibition
      (GABAergic activity). Arresting of seizure activity is carried out by restoration
      of neurotransmitter balance. This process has a direct relation with ion channel
      permeability in cell and ion transmembrane movement. Low frequency EMS may have a
      neurostimulating and neuromodulating effect that is based on electromagnetic
      induction of electric field in the brain. Under the conditions of certain
      amplitude, frequency and relaxation time low-frequency electromagnetic field
      (EMF) induces depolarization of separate neurons, and changes the total cortical
      excitability in case of repeatedly carried out procedures. It was shown that the
      exposure of acoustic range EMS in GEPRs treated with GABA-A or GABA-B receptors
      antagonists decreased behavior seizure activity in response to audiogenic
      stimuli. Injection of Glutamate receptor agonist on background EMS causes seizure
      activity, but seizure manifestations have less degree compared to non-stimulated
      rats. Thus, in response to electromagnetic stimulation, the reduction or complete
      cramping of seizures can be explained by a change in the activity of the
      neurotransmitter systems.

PMID- 30204108
TI  - [PRESERVATION OF ORGANS VIABILITY BY THE HEART-LUNG BYPASS MACHINE IN THE NON
      HEART-BEATING DONORS (REVIEW)].
AB  - In a wide range of acute, debatable problems of transplantology, the problem of
      donation should be highlighted. It includes the selection and management of the
      donors, ethical and religious aspects and issues on the prevention, treatment and
      rehabilitation of the organ before its transplantation. Among the many methods of
      organ preservation, in the last decade, machine perfusion methods are on the
      forefront. They are designed to minimize or repair the ischemic-reperfusion
      damages in tissues and cells. This became possible in conditions of technical
      progress and the introduction of artificial circulation systems that provide
      adequate tissue microcirculation in non-heart-beating donors. However, this
      approach should take into account the complexity of the perfusion machines
      design, its various connection schemes and the nature of the perfusion parameters
      - the composition and temperature of the perfusion liquor. Experimental studies
      confirm that the use of machine perfusion is a technology whose possibilities
      will radically change the approaches to organ transplantation.

PMID- 30204109
TI  - ANTINOCICEPTIVE TOLERANCE TO NSAIDS PARTIALLY MEDIATED VIA ENDOCANNABINOIDS IN
      ANTERIOR CINGULATE CORTEX OF RATS.
AB  - Pain is characterized as a complex experience, dependent not only on the
      regulation of nociceptive sensory systems but also on the activation of
      mechanisms that control emotional processes in limbic brain areas. Non-opioid,
      non-steroidal anti-inflammatory drugs (NSAIDs) are the most widely used
      analgesics in the treatment of not-severe pain. We have recently shown that
      repeated doses result in tolerance to these drugs like opioids. Here we
      investigated the central brain mechanisms of non-opioid induced antinociception
      in the non-acute pain models of rats, such as the 'formalin test' and a relation
      between administration of NSAIDs in the limbic brain area, - the anterior
      cingulated cortex (ACC), - and the endocannabinoid system. We measured
      nociceptive thermal paw withdrawal latencies and mechanical thresholds
      monolaterally in rats following microinjections of NSAIDs (diclofenac,
      ketoprofen, xefocam), saline or the cannabinoid receptor 1 (CB1) antagonist (AM
      251) in the ACC. Five min following intraplantar formalin injection all animals
      showed a significant reduction in thermal paw withdrawal latency and mechanical
      withdrawal threshold compared to pre-baseline values. Fifteen minutes after
      formalin injection, diclofenac, ketoprofen, xefocam clearly showed
      antinociceptive effects of NSAIDs. When pretreated with AM-251 we found a
      significant reduction of analgesic effects of NSAIDs. The present data support
      the notion that endocannabinoids' CB1 receptor contributes in part to
      antinociceptive effects of NSAIDs and probably involved in activation of the
      descending opioid modulatory system of pain.

PMID- 30204110
TI  - CONTENT OF CATECHOLAMINES IN BLOOD SERUM OF RATS UNDER FLUORIDE INTOXICATION.
AB  - The aim of the research was to determine in the experiment the content of
      catecholamines in serum of rats exposed to sodium fluoride. The studies were
      conducted on adult Wistar rats, subjected to oral exposure by means of a probe
      with aqueous solutions of sodium fluoride (SF) once daily, for 60 days at doses
      of 1/10, 1/100 and 1/1000 DL50, which correspondingly amounts to 20 mg/kg, 2
      mg/kg and 0.2 mg/kg of body weight. Toxification of rats at a dose of 1/100 DL50
      for 60 days and at a dose of 1/10 DL50 for 50 days was accompanied by an increase
      in blood levels of norepinephrine and epinephrine, indicating the hyperactivation
      of the mediator and hormonal parts of the sympathoadrenal system, and tension of
      the protective and adaptive reactions of the organism. Prolonged
      hypercatecholemia may become a pathogenic factor due to intensification of the
      quinidine route of oxidation of norepinephrine and epinephrine with the formation
      of reactive radicals and active forms of oxygen. Reduced serum content of
      catecholamines on the 60th day of oral administration at a dose of 1/10 DL50
      reflects, on the one hand, a decrease in their tissue deposit, and, on the other,
      a decrease in the activity and reserve capacities of the sympathoadrenal system.

PMID- 30204111
TI  - [MORPHOMETRIC ANALYSIS IN THE ZONE OF CONTACT OF VARIOUS TYPES OF IMPLANTS AND
      TISSUE OF KIDNEYS OF THE RATS EARLY TIME EXPERIMENT].
AB  - To this day, limiting the amount of sampling of donor tissue and organs, tissue
      rejection issues and numerous possible complications remain unresolved problems
      and are an actual problem of practical urology. This provision indicates the
      existence of a need to find alternative methods for solving this problem. The aim
      of the study was to study and compare the morphometric values of various types of
      implants with the tissue of the kidneys of rats in the early periods. The object
      of a comparative experimental study was decellularized bovine - derived tissue
      and a macroporous partially absorbable light UltraPro mesh. The experimental
      subjects were 48 white non-linear short-haired sexually mature rats of both sexes
      weighing 180-220 g. The autopsy days of experiment on 7 day, x 21 day sand 30
      days. The micropreparations are colored with hematoxylin and eosin. The
      decellularized bovine - derived tissue absence inflammatory and destructive
      changes in the implantation zone, compared by the mesh UltraPro. Consequently
      .these results in the study groups indicate that the implants are biocompatible
      and do not generate the manifest forms of the heperergic immune response in the
      rat tissue, since they absence persistence and progression of the exudative
      reaction.

PMID- 30204112
TI  - THE ROLE OF TRANSIENT RECEPTOR POTENTIAL (TRPA1) CHANNEL IN PRURITUS.
AB  - Pruritus or itch is defined as the sensation that causes the desire to scratch,
      and it can be induced by mechanical, thermal and chemical stimuli. Persistent
      itch accompanying diseases of the skin and other organs can significantly impair
      the quality of life. There is a growing body of evidence implicating abnormal
      transient receptor potential (TRP) channel function, as a product of excessive or
      deficient channel activity, in pathological skin conditions such as pruritus and
      dermatitis. These data supports the notion that non-histaminergic itch mediators
      require the activation of TRPA1 channel that has previously been implicated in
      pain and thermal sensation. In the present paper, we investigated whether
      chemical inducers of itch, including non-histaminergic mediators, elicit signs of
      thermal and mechanical hyperalgesia (increased pain to a noxious stimulus). We
      measured nociceptive thermal paw withdrawal latencies and mechanical thresholds
      bilaterally in mice at various time points following intraplantar injection of
      non-histaminergic mediators like as chloroquine and the bovine adrenal medulla
      peptide 8-22 (BAM8-22) producing hyperalgesia. We showed that chloroquine and
      BAM8-22 induced statistically significant dose-dependence hyperalgesia compare to
      vehicle control in both test. When pretreated with the TRPA1 antagonist (HC
      030031) we found a significant attenuation of thermal and mechanical
      hyperalgesia. We showed, thus, for the first time that non-histaminergic
      pruritogens elicit thermal and mechanical hyperalgesia through the activation of
      TRPA1 channel.

PMID- 30204113
TI  - THE ROLE OF POLYMORPHISM ASP299GLY OF THE GENE TLR 4 IN PATIENTS CO-INFECTED WITH
      HIV/HCV.
AB  - For the first time it was conducted complex research of metabolic disorders in
      patients co-infected with HIV/HCV and was shown that they are characterized by
      disturbances of mineral, lipid and carbohydrate metabolism types. It was
      established significantly higher values of indicators of mineral, lipid and
      carbohydrate metabolism types in patients co-infected with HIV/HCV compared with
      patients with chronic hepatitis C and HIV-infected persons. In patients co
      infected HIV/HCV appears significantly more frequent the polymorphism Asp299Gly
      of the gene TLR4 (chi2 = 4,5; p<0,05) when compared with healthy donors, which
      plays a significant role in the development of metabolic disorders, such
      correlation is confirmed by those relationships: a strong direct relationship
      between the polymorphism Asp299Gly of TLR4 gene and the content of insulin (r =
      0,66; p<0,001), insulin resistance (r=0,66; p<0,001), the absolute number of
      CD45+ of T-lymphocytes (r=0 45; p<0,001); a moderate direct relationship with the
      content of TNF-alpha (r=0,32; p<0,05), CRP (r=0,34; p<0,05), the absolute number
      of CD3+ of T-lymphocytes (r=0,34; p<0,05), the content of triglyceride (r=0,39;
      p<0,02), moderate inverse relationship with the zinc content (r = -0,34; p<0,05
      ), the relative number of CD4 +,% (r = -0,32; p<0,05). The system of monitoring
      of metabolic disorders in patients co-infected with HIV/HCV based on the
      definition of polymorphism Asp299Gly gene TLR4, the presence of which indicates a
      high risk of metabolic disturbances (OR=23,3; p<0,05) and requires further
      investigation, namely the definition of an index of insulin resistance, insulin
      levels, TNF-alpha, C-reactive protein, zinc and triglyceride levels in dynamics
      at intervals of 6 months that allow for timely diagnosis and correction of
      metabolic disorders.

PMID- 30204114
TI  - [HLA ALLELES IN KAZAKHSTAN AND IN THE GLOBAL GENOFUND].
AB  - The HLA alleles in the Kazakhstan genofund and in the global genofund were
      compared. The study was carried out on 2283 Kazakhstan donors, 4 566 antigens by
      five locuses A, B, C, DRB1, DQB1. Comparison with the global HLA alleles was
      carried out using http://www.allelefrequencies.net open internet resource created
      by the Royal Liverpool University Hospital. The database included information on
      8 locuses (A, B, C, DRB1, DPA1, DPB1, DQA1, DQB1), collected in different
      programs for HLA genofund studies (anthropological research, blood and bone
      marrow donorship, HLA-associated diseases, etc.). The results demonstrated the
      need in further development of the hemopoietic stem cell (HSC) donor register in
      the Republic for more effective search for compatible donors.

PMID- 30204115
TI  - NICORANDIL EFFICACY IN THE TREATMENT OF ISCHEMIC HEART DISEASE (REVIEW).
AB  - Nicorandil is an antianginal agent with a dual mechanism of action. It belongs to
      ATP-senitive potassium channel openers which has the beneficial effect in angina
      pectoris, playing an significant role in the dilation of arteries, veins and
      coronary artery. It leads to the relaxation of vascular smooth muscle and causes
      vasodilatation of major epicardial vessels. This effect is crucial for reducing
      risks of further damage in cases when percutaneous coronary intervention (PCI) is
      necessary. Relevant new studies concluded that Nicorandil has antiarrhythmic and
      cardioprotective effects by improving reperfusion, ultimately leading to a
      reduction in microvascular damage caused by PCI. Furthermore, Nicorandil addition
      to the standard therapy of paitents with ischemic heart disease has demonstrated
      improved quality of life.

PMID- 30204116
TI  - IMMUNOHISTOCHEMICAL ANALYSIS OF THE INDUCIBLE AND ENDOTHELIAL FRACTIONS OF NO
      SYNTHASE IN THE INTENSTINAL MUCOSA OF COLO-COLONIC ANASTOMOSIS UNDER INFLUENCE OF
      CHRONIC STRESS AND THIOTRIAZOLINE APPLICATION.
AB  - UUnder stress in the development of metabolic disorders, nitric oxide (NO)
      occupies a significant place. Dependence of the metabolism of NO indicates its
      important role in the pathogenesis of diseases of the gastrointestinal tract. The
      aim of the study is to study immunohistochemical changes in the colon after the
      large bowel resection and the effect of stress and correction of thiatriazoline.
      The experiment was performed on 86 male rats. After considering the results of
      our examination, a long-term exposure to stress of the experimental animals leads
      to a significant increase of the inducible expression of NO - synthase fractions
      (iNOs) in the cells of the mucous membrane of the large bowel in the zone of
      anastomosis. Under the conditions of chronic immobilization stress, the use of
      tiotriazolini enhances the expression of the constitutive endothelial isoform of
      NO - synthase in the endothelium of blood vessels in comparison with the animals,
      which were exposed to stress and underwent resection without drug correction. The
      intraperitoneal injection of tiotriazolini better regulates stress-mediated
      changes in the expression of inducible and endothelial isoforms of NO - synthase
      and normalizes the content of nitrogen oxide in the large bowel of the rats
      during the final stages, while subserous injection is more effective in the early
      stages of examination, that reflects the compensation of the endothelial
      dysfunction and the reduction of the effect of nitrogen oxide.

PMID- 30204117
TI  - HISTOLOGICAL CHANGES IN SPLEEN UNDER CONDITIONS OF TOXIC CARCINOGENESIS.
AB  - Under development of dimethylhydrazine-induced adenocarcinomatosis of the large
      intestine in white outbred male rats morphological changes of the structural
      components of the spleen were studied. It was found, that the progression of
      experimental carcinogenesis is accompanied by severe violations of the
      morphological state of all structural components of the spleen, manifested by
      destructively degenerative changes of the stroma, red and white pulp and
      significant vascular disorders. The severity of the pathomorphological changes in
      the spleen increases directly proportionally to the increase of the duration of
      the oncogenic factor impact.

PMID- 30204118
TI  - EPIDEMIOLOGY OF CARBAPENEM-RESISTANT KLEBSIELLA PNEUMONIAE IN INTENSIVE CARE
      UNITS OF MULTIPROFILE HOSPITALS IN TBILISI, GEORGIA.
AB  - Klebsiella pneumoniae is one of the most frequent cause of health care associated
      infections. Dissemination of carbapenem-resistant (CR) K. pneumoniae infections
      significantly trend toward patient morbidity, length of stay and mortality. The
      aim of this research was to study prevalence and risk-factors of CR K. pneumoniae
      in Georgia. To identify risk factors for hospital-acquired carbapenem-resistant
      (CR) K. pneumoniae, from January 1, 2017 through February 28, 2018, an
      observational case-control study was performed in the ICUs of two tertiary-care
      hospitals in Tbilisi (High Medical Technology Centre and Ghudushauri National
      Medical Centre). All isolated K. pneumoniae cultures were tested on antibiotic
      susceptibility tests (AST). AST was performed by disk diffusion methods and E
      test for MIC detection. For the first time CR K. pneumoniae isolates were
      screened for the presence of KPC, VIM, IMP, NDM and OXA carbapenemase in a PCR.
      Totally, 46 cultures of K. pneumoniae were isolated. Among them 20 (43.5%) were
      resistant to carbapenems. Most frequently CR K. pneumoniae cultures were isolated
      in patients with ventilator associated pneumonia (75%). Main risk factors of
      carbapenem-resistant from invasive procedures were: mechanical ventilation (OR
      30.4, 95% CI 3.504-263.752, p=0.0003), nasogastric tube (OR 17.0, 95% CI 3.202
      90.257, p=0.0002), central venous catheter (OR 10.06, 95% CI 1.152-87.849,
      p=0.028) and previous use of antibiotics (OR 10.059, 95% CI 1.152-87.849,
      p=0.028), especially carbapenem and 3rd generation cephalosporin. Predominant is
      OXA-producing K. pneumoniae, NDM-producing K. pneumoniae is relatively rare. To
      control dissemination of CR K. pneumoniae infection prevention and control should
      be toughened in medical facilities, and screening for early detection of patients
      with CR K. pneumoniae should be done.

PMID- 30204119
TI  - INTERACTIONS OF RANKL, OSTEOPROTEGERIN AND ADIPOKINES IN REGULATION OF BONE
      REMODELING IN EXPERIMENTAL CHRONIC KIDNEY FUNCTION DISORDER.
AB  - RANKL and osteoprotegerin are the key cytokines of the axis regulating not only
      bone remodeling but also bone-kidney interrelations. They are connected with
      adipokines in the regulatory actions. The aim of the article was to investigate
      the role of the main parts of RANK-RANKL-osteoprotegerin axis and cytokines of
      additional link of regulatory network - adiponectin and visfatin and the
      interrelationship of these cytokines in chronic kidney disorder model in rats.
      Chronic kidney disorder model was created in the rats 12 weeks after
      intramuscular 50 % glycerol injection-induced acute kidney injury. RANKL,
      osteoprotegerin, adiponectin and visfatin levels was measured using ELISA.
      Increase of all cytokines and changes of their interrelations has been revealed
      in rats with chronic kidney disorder model. Conclusion was made that effects of
      the cytokine axis where RANKL is a trigger in the regulation network of
      interconnections "bone - kidney" has inflammatory character, so as visfatin
      effect, and adiponectin has opposite preserving bone effect.

PMID- 30204120
TI  - SYNTHESIS OF THE NEW 2-(3,4-DIHYDRO-3-OXO-2H-[1,2,4]TRIAZINO[4,3-C]QUINAZOLIN-4
      YL) ACETIC ACID DERIVATIVES AND ANALYSIS OF THEIR ANTIOXIDANT ACTIVITY IN
      NITROSATIVE STRESS MODELS.
AB  - Today we know that NO. and ONOO- are clue pathophysiological factors for
      progression some ischemic diseases of the central nervous system. So
      investigation of the antioxidants which will be able to decrease NO. and ONOO-
      toxicity seems to be very of current interest. The six esters and three amides of
      2-(3,4-dihydro-3-oxo-2H-[1,2,4]triazino[4,3-c]quinazolin-4-yl)acetic acid were
      synthesized for this study, and we showed evidence of antioxidant activity of
      these new original derivatives. We studied the effect of 2-(3,4-dihydro-3-oxo-2H
      [1,2,4]triazino[4,3-c]quinazolin-4-yl)acetic acid derivatives on superoxide
      dismutase activity under the condition of excessive NO. and ONOO- production. NO.
      induction was performed by the action of light on sodium nitroprusside
      Na2[Fe(NO)(CN)5]*2H2O in vitro. Also, the investigation of the substances was
      carried out in the brain supernatant obtained from the white Wistar rats in vivo.
      For nitrosative stress modeling dinitrozolic complex of Fe2+ and cysteine were
      utilized. Our data showed that 2-(3,4-dihydro-3-oxo-2H-[1,2,4]triazino[4,3
      c]quinazolin-4-yl)acetic acid is not active compound while its esters and amides
      have antioxidant activity. Compound benzyl ester of this acid revealed the most
      effective antioxidant activity.

PMID- 30204121
TI  - [COMPARATIVE ANALYSIS OF THE ASSORTMENT OF HOMEOPATHIC MEDICINES IN THE
      PHARMACEUTICAL MARKET OF UKRAINE, THE RUSSIAN FEDERATION, THE REPUBLIC OF BELARUS
      AND KAZAKHSTAN].
AB  - THE AIM OF THE STUDY: analysis of the assortment of homeopathic medicinal (HoM)
      in the pharmaceutical market of Ukraine in comparison with the market of the
      Russian Federation, the Republic of Belarus and Kazakhstan for further provision
      of recommendations on possible scientific and practical directions, expansion of
      the HoM nomenclature in the Ukrainian pharmaceutical market. The objects of
      research were State registers of medicines of Ukraine, the Russian Federation,
      the Republic of Belarus and Kazakhstan as of 01.01.2018. In the process of
      research, scientific methods of analysis, systematization and generalization,
      scientific literature were used. The comparative analysis of the State Drug
      Registries of Ukraine, the Russian Federation, the Republic of Belarus and
      Kazakhstan showed that Russia is the leader in the number of registered drugs. In
      the analyzed markets, the main segment of HoM is occupied by solid dosage forms.
      Only in the Ukrainian market - solid and liquid in the same ratio. It is
      determined that the main producers of HoM are Germany, Austria, the Russian
      Federation. Analysis by pharmacotherapeutic groups showed that only in the
      Russian Federation market HoM are represented by all 14 pharmacotherapeutic
      groups according to ATC-classification. In the Republics of Belarus and
      Kazakhstan, drugs from 9 groups are available on the market. On the
      pharmaceutical market of Ukraine HoM are represented by 11 pharmacotherapeutic
      groups of 14 existing ones. It was revealed that for today the markets for
      Ukraine, Belarus and Kazakhstan are relevant is the expansion of the range of
      HoM, the increase in the share of drugs of domestic production, which will lead
      to an increase in both physical and economic accessibility of HoM for the
      population.

PMID- 30204122
TI  - [ESTIMATION OF EFFICIENCY OF HOSPITAL PAYMENT METHODS IN THE REPUBLIC OF
      KAZAKHSTAN].
AB  - Purpose - to evaluate the methods of payment for medical aid in the medical
      organizations of the Republic of Kazakhstan. The materials of the study were
      statistical and financial indicators of the activity of medical organizations of
      the Republic of Kazakhstan for 2010-2017. The research is based on methods of
      organizational and economic research: theoretical analysis, economic and
      statistical analysis. With the implementation of the system of "global budget" at
      the Regional Oncologic Dispensary main target indicators of the memorandum was
      reached with the year 2011-2015. With the introduction of the system, the beds
      were reduced by 33.3%, but due to the increase in beds in the day hospital, the
      number of patients treated increased by 55.8%. In the Tayinshinsky Central
      District Hospital, the increase in funding by 26.7% and wages of medical workers
      by 24.9%. Thus, the application in the domestic practice of global budget systems
      and payment for diagnosis-related groups in a hospital environment showed its
      effectiveness, proving that the payment system is designed to stimulate
      efficiency gains and to prevent the provision of unnecessary services. At the
      same time, a number of negative aspects of payment methods can be identified,
      which requires a further revision of the diagnosis-related groups in order to
      improve the efficiency of using budget funds. Payment of medical services for the
      global budget system, in particular oncological services also require a number of
      changes on the part of the regulatory normative legal acts.

PMID- 30204123
TI  - Electrically tunable optical properties of few-layer black arsenic phosphorus.
AB  - Black arsenic phosphorus (b-AsP) is a promising two-dimensional material for
      various optoelectronic applications, bridging the wavelength gap between two
      dimensional molybdenum disulfide and graphene. In particular, it has intriguing
      potential in photodetectors and great advantages in the mid-infrared field.
      However, its optoelectronic modulation has yet to be elucidated, which requires a
      fundamental understanding of its field-effect optical modulation. Here, we report
      the measurements of the lower-energy infrared anisotropic optical response of
      thin b-AsP under different electrical gating. We reveal that in addition to band
      edge absorption, amplitude modulation of sub-band absorption up to ten percent is
      also obtained in reflection extinction. These in-gap absorptions are attributed
      to spin-orbital coupling and free carrier absorption. Our results suggest the
      important potential for use of b-AsP in mid-infrared optoelectronic modulator
      applications.

PMID- 30204124
TI  - Investigation of the effect of natural tumor cell death on radiotherapy outcomes.
AB  - The aim of the work is to investigate the impact of radiation-independent
      (natural or spontaneous) tumor cell death on tumor control probability (TCP)
      during and following fractionated external-beam radiotherapy employing both
      analytical and numerical methods. The analytical method solves a TCP model
      accounting for tumor repopulation and non-radiation tumor cell death during
      fractionated external-beam radiotherapy. The numerical method is based on a Monte
      Carlo simulation of the processes of radiation-induced cell kill, as well as cell
      division and natural cell death randomly taking place in the time interval
      between fractions. Distributions of the number of surviving cells are constructed
      using the Monte Carlo method for cases with and without natural cell death. The
      analytically and numerically calculated values of TCP were found to be in
      excellent agreement (as shown in the Method and materials section), thereby
      validating both methods. The TCP model is then fitted to two different
      experimental data sets with the aim of determining the model parameter values,
      primarily the natural death rate. Two versions of the linear-quadratic model of
      cell damage-with and without assumed re-sensitization of the tumor cells during
      treatment-are used. In two of the fits a strong correlation between the
      repopulation and spontaneous cell death rates is observed. It was possible to
      determine separately the values of the two rates only in the fit of the model
      with resensitization to the most diversified data set consisting of seven
      different fractionation regimes. The observed correlation together with a
      theoretical consideration leads to the conclusion that in most cases it is the
      net effect of the two processes of birth and death rather than the processes
      separately that determines treatment outcome. However, depending on the values of
      the rates of the two processes and the duration of the treatment, the treatment
      outcome may be more accurately determined by the absolute values of the two rates
      rather than just by their difference.

PMID- 30204125
TI  - Shared-photodetector readout to improve the sensitivity of positron emission
      tomography.
AB  - Sensitivity is an important performance characteristic of positron emission
      tomography (PET) systems. Improved sensitivity can be used to reduce injected
      dose, reduce scan time, or improve the signal-to-noise ratio and temporal
      resolution for dynamic studies. One way to improve the sensitivity of PET
      scanners is to reduce the gaps between detector modules. In this paper, a new
      signal processing method, named the shared-photodetector readout method, is
      proposed and evaluated. In this method, the signals generated in nearest neighbor
      photodetectors adjacent to the detector module of interest, were used to help
      identify the interaction location in the detector module of interest. Using this
      method, scintillator array-based detector modules with almost 100% packing
      fraction can be built, and the edge crystals can be clearly resolved, even when
      the crystals are small compared to the photodetector size. To evaluate this
      signal processing concept in one dimension, a detector block with four dual-ended
      readout detector modules, was designed. The detector block consisted of eight 4 
      *  4 arrays of SensL MicroFJ-30035 SiPMs coupled to both ends of a 14  *  56
      array of 0.9  *  0.9  *  20 mm3 LYSO elements with a pitch size of 0.96 mm and a
      length of 20 mm. Performance in terms of energy resolution, flood histogram,
      timing resolution and depth-of-interaction resolution obtained using the shared
      photodetector readout method were compared to those obtained using a conventional
      readout method. The results show that better over-all performance was achieved
      using the shared-photodetector readout method, especially at the edges and
      corners of the array.

PMID- 30204126
TI  - Bimetallic nanoporous Pd-Ag prepared by dealloying with polyvinylpyrrolidone and
      their electrocatalytic properties.
AB  - Bimetallic nanoporous Pd-Ag solid solution alloys with hierarchical structure
      were prepared by dealloying melt-spun Al-Pd-Ag ribbons in a 10 wt% H3PO4
      solution. Electrocatalytic properties of nanoporous Pd-Ag alloys were measured in
      comparison with the nanoporous Pd without Ag. Experimental results showed that
      the nanoporous Pd-Ag alloys displayed electrocatalytic properties superior to
      their Ag-free counterparts. In particular, the optimised composition was revealed
      to be Pd/Ag = 3/2 in atomic ratio in the precursor with fixed 85 at% Al alloys,
      which yielded in a peak current density in the nanoporous Pd-Ag alloy two times
      that of the pure Pd one. The electrocatalytic activity of nanoporous Pd-Ag alloy
      with refined microstructure was further increased up to three times of the pure
      Pd one by adding 1 mM polyvinylpyrrolidone (PVP) into the H3PO4 solution. The
      underlying mechanism of refinement was related to a restriction effect on the
      free diffusion of Pd and Ag under adsorption of the PVP macromolecules. The
      significant improvement in the electrocatalytic properties was attributed to the
      dual promotion by the electron transfer from PVP to Pd-Ag and by a synergistic
      effect between Pd and Ag.

PMID- 30204127
TI  - Human-agent co-adaptation using error-related potentials.
AB  - OBJECTIVE: Error-related potentials (ErrP) have been proposed as an intuitive
      feedback signal decoded from the ongoing electroencephalogram (EEG) of a human
      observer for improving human-robot interaction (HRI). While recent demonstrations
      of this approach have successfully studied the use of ErrPs as a teaching signal
      for robot skill learning, so far, no efforts have been made towards HRI scenarios
      where mutual adaptations between human and robot are expected or required. These
      are collaborative or social interactive scenarios without predefined dominancy of
      the human partner and robots being perceived as intentional agents. Here we
      explore the usability of ErrPs as a feedback signal from the human for mediating
      co-adaptation in human-robot interaction. APPROACH: We experimentally demonstrate
      ErrPs-based mediation of co-adaptation in a human-robot interaction study where
      successful interaction depended on co-adaptive convergence to a consensus between
      them. While subjects adapted to the robot by reflecting upon its behavior, the
      robot adapted its behavior based on ErrPs decoded online from the human partner's
      ongoing EEG. MAIN RESULTS: ErrPs were decoded online in single trial with an avg.
      accuracy of 81.8%  +/-  8.0% across 13 subjects, which was sufficient for
      effective adaptation of robot behavior. Successful co-adaptation was demonstrated
      by significant improvements in human-robot interaction efficacy and efficiency,
      and by the robot behavior that emerged during co-adaptation. These results
      indicate the potential of ErrPs as a useful feedback signal for mediating co
      adaptation in human-robot interaction as demonstrated in a practical example.
      SIGNIFICANCE: As robots become more widely embedded in society, methods for
      aligning them to human expectations and conventions will become increasingly
      important in the future. In this quest, ErrPs may constitute a promising
      complementary feedback signal for guiding adaptations towards human preferences.
      In this paper we extended previous research to less constrained HRI scenarios
      where mutual adaptations between human and robot are expected or required.

PMID- 30204128
TI  - Inadequate ubiquitination-proteasome coupling contributes to myocardial ischemia
      reperfusion injury.
AB  - The ubiquitin-proteasome system (UPS) degrades a protein molecule via 2 main
      steps: ubiquitination and proteasomal degradation. Extraproteasomal ubiquitin
      receptors are thought to couple the 2 steps, but this proposition has not been
      tested in vivo with vertebrates. More importantly, impaired UPS performance plays
      a major role in cardiac pathogenesis, including myocardial ischemia-reperfusion
      injury (IRI), but the molecular basis of UPS impairment remains poorly
      understood. Ubiquilin1 is a bona fide extraproteasomal ubiquitin receptor. Here,
      we report that mice with a cardiomyocyte-restricted knockout of Ubiquilin1
      (Ubqln1-CKO mice) accumulated a surrogate UPS substrate (GFPdgn) and increased
      myocardial ubiquitinated proteins without altering proteasome activities,
      resulting in late-onset cardiomyopathy and a markedly shortened life span. When
      subject to regional myocardial ischemia-reperfusion, young Ubqln1-CKO mice showed
      substantially exacerbated cardiac malfunction and enlarged infarct size, and
      conversely, mice with transgenic Ubqln1 overexpression displayed attenuated IRI.
      Furthermore, Ubqln1 overexpression facilitated proteasomal degradation of
      oxidized proteins and the degradation of a UPS surrogate substrate in cultured
      cardiomyocytes without increasing autophagic flux. These findings demonstrate
      that Ubiquilin1 is essential to cardiac ubiquitination-proteasome coupling and
      that an inadequacy in the coupling represents a major pathogenic factor for
      myocardial IRI; therefore, strategies to strengthen coupling have the potential
      to reduce IRI.

PMID- 30204129
TI  - HIC1 deletion promotes breast cancer progression by activating tumor
      cell/fibroblast crosstalk.
AB  - Breast cancer (BrCa) is the malignant tumor that most seriously threatens female
      health; however, the molecular mechanism underlying its progression remains
      unclear. Here, we found that conditional deletion of hypermethylated in cancer 1
      (HIC1) in the mouse mammary gland might contribute to premalignant transformation
      in the early stage of tumor formation. Moreover, the chemokine (C-X-C motif)
      ligand 14 (CXCL14) secreted by HIC1-deleted BrCa cells bound to its cognate
      receptor GPR85 on mammary fibroblasts in the microenvironment and was responsible
      for activating these fibroblasts via the ERK1/2, Akt, and neddylation pathways,
      whereas the activated fibroblasts promoted BrCa progression via the induction of
      epithelial-mesenchymal transition (EMT) by the C-C chemokine ligand 17 (CCL17)/CC
      chemokine receptor 4 (CCR4) axis. Finally, we confirmed that the HIC1-CXCL14
      CCL17 loop was associated with the malignant progression of BrCa. Therefore, the
      crosstalk between HIC1-deleted BrCa cells and mammary fibroblasts might play a
      critical role in BrCa development. Exploring the progression of BrCa from the
      perspective of microenvironment will be beneficial for identifying the potential
      prognostic markers of breast tumor and providing more effective treatment
      strategies.

PMID- 30204130
TI  - Feasibility and clinical benefit of the cognitive-behavioral intervention for
      preparing patients for transesophageal echocardiographic study.

PMID- 30204131
TI  - Coexistence of Wolff-Parkinson-White and Brugada ECG.

PMID- 30204132
TI  - The relationship between echocardiographic epicardial adipose tissue and P wave
      dispersion and corrected QT- interval.

PMID- 30204133
TI  - Cardiac syndrome X: An important cause of microvascular angina.

PMID- 30204134
TI  - Influence of smoking habits on acute outcome of revascularization of chronic
      total occlusion.
AB  - OBJECTIVE: Percutaneous coronary intervention (PCI) for chronic total occlusion
      (CTO) remains a major challenge in interventional cardiology. The exact toxic
      components of cigarette smoke and the mechanisms involved in smoking-related
      cardiovascular dysfunction are largely unknown, but it increases inflammation,
      thrombosis, and oxidation of low-density lipoprotein cholesterol. There is only
      insignificant knowledge reported in the literature about the influence of smoking
      habits on acute outcome in CTO PCI. METHODS: Between 2012 and 2017, a total of
      559 patients were included in the study. The patients all underwent PCI for at
      least 1 CTO. Antegrade and retrograde CTO techniques were applied. The Shapiro
      Wilk test was used to test for normality of distribution. Continuous variables
      were tested for differences with the Kruskal-Wallis test or the Mann-Whitney U
      test, as appropriate. Categorical variables were tested using Fisher's exact
      test. RESULTS: Non-smokers were older than smoking patients (65.3+/-10.3 years
      vs. 58.3+/-9.2 years; p<0.001). The mean age of the cohort was 62.1 years (+/
      10.5). Smokers were more often male (85.7% vs. 79.7%; p=0.074), suffered from
      longer lesion length (36.1+/-17.5 mm vs. 39.1+/-17.2 mm; p=0.023) and therefore
      needed longer stents (64.2+/-26.5 mm vs. 69.0+/-28.0 mm; p=0.084). The success
      rate was comparable for smokers and non-smokers. In-hospital procedural
      complications were rare and demonstrated no statistically significant difference.
      CONCLUSION: The results of this retrospective study revealed no significant
      association between smoking and acute outcome in CTO PCI. Smokers did, however,
      have longer lesions and needed longer stents.

PMID- 30204135
TI  - [Increased myocardial energy expenditure in cardiac syndrome X: More work, more
      pain].
AB  - OBJECTIVE: The aim of this study was to assess the myocardial energy expenditure
      (MEE) in patients with cardiac syndrome X (CSX) and to examine its association
      with exercise electrocardiogram (ECG) parameters. METHODS: A total of 99 patients
      who underwent coronary angiography and who were diagnosed as having normal
      coronary arteries were included. The patients were divided into 2 groups based on
      symptoms and exercise ECG parameters: 56 CSX patients and 43 control patients
      with a negative stress test. MEE was calculated using transthoracic
      echocardiography-derived parameters: circumferential end-systolic stress, left
      ventricular ejection time, and stroke volume. RESULTS: In patients with CSX, the
      MEE at rest was 28% higher in than the control group (89.2+/-36.3 vs. 69.8+/-17.2
      cal/minute). Correlation analysis revealed a moderately negative correlation
      between MEE and the Duke treadmill score (DTS) (beta:-0.456; p<0.001). Receiver
      operating characteristic analysis with a cut-off value of 74.6 cal/minute for MEE
      had a sensitivity of 78.1% and a specificity of 75.3% for the prediction of CSX
      (area under the curve: 0.872; p<0.001). An extra 1 calorie spent per minute at
      rest increased the likelihood of CSX by about 86% (odds ratio: 1.863).
      CONCLUSION: This study demonstrated that MEE was greater in CSX patients compared
      with a control group. Increased MEE was determined to be an independent predictor
      of CSX. DTS was inversely correlated with MEE. Increased MEE may have a crucial
      role in CSX pathophysiology.

PMID- 30204136
TI  - Association between SYNTAX II score and electrocardiographic evidence of no
      reflow in patients with ST-segment elevation myocardial infarction.
AB  - OBJECTIVE: This study was performed to examine the association between the SYNTAX
      II score (SS-II) and no-reflow observed on electrocardiography and examine their
      use in the evaluation of risk of an in-hospital major adverse cardiovascular
      event (MACE) in patients with ST-segment elevation myocardial infarction (STEMI).
      METHODS: A total of 126 consecutive STEMI patients who underwent primary
      percutaneous coronary intervention (pPCI) were recruited. The SS-II was derived
      using angiographic and basic patient clinical features. The difference in the sum
      of Stsegment elevations measured between before the pPCI and the assessment
      determined approximately 60 minutes after the pPCI was interpreted as the sum of
      ST-segment resolution (SigmaSTR). MACE is a composite endpoint frequently used in
      cardiovascular research and usually includes endpoints reflecting safety and
      effectiveness. SigmaSTR <50% was defined as incomplete SigmaSTR (no-reflow group;
      n=44), while SigmaSTR <50% was defined as complete SigmaSTR (normal-flow group,
      n=82). RESULTS: The SS-II was significantly higher in the no-reflow group
      (p<0.001). SS-II and no-reflow findings were associated with MACE. Logistic
      regression analysis demonstrated significant predictive values of SS-II (Odds
      ratio [OR]: 1.169; 95% confidence interval [CI]: 1.084-1.260; p<0.001) and
      SigmaSTR (OR: 0.764; 95% CI: 0.632-0.924; p=0.006) for in-hospital MACE.
      CONCLUSION: SS-II was significantly associated with no-reflow as assessed by
      electrocardiography. In patients with STEMI, SS-II and no-reflow (incomplete
      SigmaSTR) may be important predictive factors for in-hospital MACE.

PMID- 30204137
TI  - Gold-tip versus contact-sensing catheter for cavotricuspid isthmus ablation: A
      comparative study.
AB  - OBJECTIVE: Radiofrequency (RF) ablation is a highly successful procedure for the
      management of typical atrial flutter (AFL), an abnormal heart rhythm originating
      within the atria. There is no strong evidence that the use of contact force (CF)
      has any impact on procedural duration or acute success in the management of
      cavotricuspid isthmus (CTI)-dependent AFL. The aim of this study was to compare
      acute procedural parameters using a non-CF, 4-mm, gold-tip, irrigated catheter
      and a CF-sensing catheter in patients with AFL. METHODS: This was a retrospective
      cohort study. Consecutive patients who underwent typical AFL catheter ablation
      with either a gold-tip or CF-sensing catheter were enrolled. The procedural
      parameters obtained were: time to achieve bidirectional block, time to terminate
      AFL, total duration of RF application, procedure duration, fluoroscopy time,
      acute reconnection within 20 minutes following the last RF application, and
      procedural complications. RESULTS: Of the 40 patients screened, 37 were included
      in the study. The procedural endpoint of bidirectional isthmus block was achieved
      in all patients. The use of gold-tip catheters was associated with a shorter
      length of time to achieve bidirectional block (median time: 20.0 minutes
      [interquartile range {IQR}: 12.0-28.0 minutes]) compared with a median time of
      36.0 minutes (IQR: 12.0-53.0 minutes; p=0.048) in the CF group. Furthermore,
      there was a trend toward reduced procedural duration in favor of the gold-tip
      catheter (median goldtip: 74.0 minutes [IQR: 57.0-84.0 minutes]; median CF: 85.0
      minutes [IQR: 57.0-107.0 minutes]; p=0.171). A greater requirement for the use of
      long sheaths was observed in cases where the CF catheter was employed for the
      procedure (CF: 11, 57.9 %; non-CF: 1, 5.6%; p=0.005). CONCLUSION: The time
      required to achieve bidirectional block, which is also reflected in the
      procedural time, was less when using a gold-tip catheter, and there was less need
      for the use of a long sheath. Further studies may be useful to evaluate this
      finding.

PMID- 30204138
TI  - The relationship between echocardiographic epicardial adipose tissue, P-wave
      dispersion, and corrected QT interval.
AB  - OBJECTIVE: Epicardial adipose tissue (EAT) secretes various pro-inflammatory and
      atherogenic substances that have several effects on the heart. The goal of this
      study was to evaluate the association between EAT thickness and both P-wave
      dispersion (Pd) and corrected QT interval (QTc), as simple, non-invasive
      indicators of arrhythmia on a surface electrocardiogram. METHODS: This
      retrospective observational study included 216 patients who had normal coronary
      arteries observed on coronary angiography. Each patient underwent 12-derivation
      electrocardiography to measure Pd and QTc, and transthoracic echocardiography to
      measure EAT thickness. The patients were divided into 2 groups according to the
      median EAT value (EAT low group: <5.35 mm; EAT high group: >=5.35 mm). RESULTS: P
      wave dispersion (p=0.001) was significantly greater in the EAT high group
      compared with the EAT low group. However, the QTc (p=0.004) was significantly
      greater in the latter group. The median left ventricular end-diastolic diameter
      (p=0.033), mean left ventricular end-systolic diameter (p=0.039), and mean left
      atrial diameter (p=0.012) were significantly greater in the EAT high group.
      Multiple logistic regression analysis using the backward elimination method
      revealed that the leukocyte count (Odds ratio [OR]: 1.000; 95% confidence
      interval [CI]: 1.000-1.000; p=0.001), Pd (OR: 1.1026; 95% CI: 1.010-1.043;
      p=0.002), QTc interval (OR: 0.988; 95% CI: 0.979-0.997; p=0.009), and left
      ventricular ejection fraction (OR: 0.922; 95% CI: 0.859-0.989; p=0.023) were
      independently associated with greater EAT thickness. CONCLUSION:
      Echocardiographic end-diastolic EAT thickness on the free wall of the right
      ventricle was associated with Pd and QTc in patients with normal coronary
      arteries.

PMID- 30204139
TI  - Depression and all-cause mortality in patients with congestive heart failure and
      an implanted cardiac device.
AB  - OBJECTIVE: The purpose of this study was to assess the association between
      depression and all-cause mortality in patients with congestive heart failure
      (CHF) and an implanted cardiac device. METHODS: The study enrolled 260 patients
      (mean age 56.8+/-10.0 years; 83.1% male) with CHF and an implanted cardiac device
      (156 patients with a resynchronization therapy cardiac device, 104 patients with
      an implantable cardioverter defibrillator). The mean duration of follow-up was
      48.6+/-32.2 months. The Beck Depression Inventory was used to measure depressive
      symptoms. Depression was considered absent for a score between 0 and 9, mild to
      moderate for a score between 10 and 18, and severe if the score was 19 or
      greater. The Cox proportional hazards regression model was used to estimate
      hazard ratios (HR) with a 95% confidence interval (CI) for the impact of
      depression on all-cause mortality. The HR was calculated after adjustment for the
      following confounders: age, gender, smoking status, hypertension, diabetes
      mellitus, body mass index, hypercholesterolemia, left ventricular ejection
      fraction, number of hemodynamically significant lesions of the coronary arteries,
      and the type of implanted cardiac device. RESULTS: During the follow-up period,
      37 patients died (14.2%). The adjusted HR of depression for all-cause mortality
      was 1.05, with a 95% CI of 1.01-1.09. Patients without depression were accepted
      as a reference group with HR=1.0 for analysis of the categorical indicator. The
      HR was 1.32, with a 95% CI of 0.57-3.03, in patients with mild depressive
      symptoms, and the HR was 3.18 with a 95% CI of 1.31-7.73 in patients with severe
      depressive symptoms. CONCLUSION: Increased depressive symptoms were independently
      associated with all-cause mortality in patients with CHF and an implanted cardiac
      device.

PMID- 30204140
TI  - Coexistence of Brugada and Wolff Parkinson White syndromes: A case report and
      review of the literature.
AB  - A 31-year-old male patient presented with complaints of palpitations, dizziness,
      and recurrent episodes of syncope. A 12-lead electrocardiogram (ECG) revealed
      manifest ventricular preexcitation, which suggested Wolff Parkinson White
      syndrome. In addition, an incomplete right bundle branch block and a 3-mm ST
      segment elevation ending with inverted T-waves in V2 were consistent with coved
      type (type 1) Brugada pattern. An electrophysiological study was performed, and
      during the mapping, the earliest ventricular activation with the shortest A-V
      interval was found on the mitral annulus posterolateral site. After successful
      radiofrequency catheter ablation of the accessory pathway, the Brugada pattern on
      the ECG changed, which prompted an ajmaline provocation test. A type 1 Brugada
      ECG pattern occurred following the administration of ajmaline. Considering the
      probable symptom combinations of these 2 coexisting syndromes and the presence of
      recurrent episodes of syncope, programmed ventricular stimulation was performed
      and subsequently, ventricular fibrillation was induced. An implantable
      cardioverter-defibrillator was implanted soon after.

PMID- 30204142
TI  - Percutaneous retrieval of embolized Amplatzer septal occluder from pulmonary
      artery using a novel method.
AB  - Percutaneous closure of atrial septal defects is accepted as a safe and effective
      treatment method. Device embolization is a rare, but potentially fatal
      complication. While embolized devices are typically removed surgically, in
      eligible cases, they can also be removed percutaneously at an experienced center.
      Presently described is the retrieval of an embolized device with a novel
      percutaneous technique.

PMID- 30204141
TI  - A new and simple technique for vagal ganglia ablation in a patient with
      functional atrioventricular block: Electroanatomical approach.
AB  - Increased parasympathetic tone may cause symptomatic functional atrioventricular
      block (AVB) and necessitate pacemaker implantation. In these patients, where
      there is no structural damage to the conduction system, removal of the vagal
      activity using radiofrequency ablation seems to be a theoretically rational
      approach. Several methods have been used to determine suitable areas for vagal
      ganglia ablation. The aim of this report was to describe a new method to detect
      parasympathetic innervation sites without the need to use additional equipment or
      extend procedure time. A 51-year-old man was referred to the clinic for
      implantation of a permanent pacemaker because of symptomatic second-degree AVB
      and recurrent syncope. The functional nature of the AVB and a supra-Hisian
      location were verified with standard electrocardiography, Holter recordings,
      atropine sulfate test, and a standard electrophysiological study. Using
      conventional recordings, the electrograms were divided into 3 subgroups and sites
      demonstrating a fractionated pattern were targeted. All of the fractionated
      electrogram sites considered suitable for usual ganglion settlement were ablated.
      Biatrial ablation was initiated from the left atrial side. During left atrial
      ablation, the intrinsic basic cycle length of sinus node accelerated to 800
      milliseconds despite AVB persistence. Subsequently, 1:1 atrioventricular
      conduction was achieved when ablation was applied around the coronary sinus
      ostium. The patient was completely asymptomatic, experiencing no episodes of
      dizziness or syncope, and was taking no medications at the end of 9 months of
      follow-up. In conclusion, electroanatomically guided vagal ganglia ablation may
      be a good alternative to pacemaker implantation in well-selected patients with
      functional AVB.

PMID- 30204143
TI  - Incidentally detected bifid cardiac apex in a patient with acute myocardial
      infarction: A case presentation and brief literature review.
AB  - A bifid cardiac apex is a rare congenital cardiac anomaly in humans and is
      usually associated with other congenital heart diseases. Presently described is a
      case of an incidentally detected bifid cardiac apex in a patient presenting with
      inferior ST-segment elevation myocardial infarction, which was subsequently
      confirmed with selective ventriculography. This anomaly, because it is rare, can
      be a source of confusion to clinicians, especially when acute coronary syndrome
      is present. The possible presence of this anomaly should, therefore, be kept in
      mind in daily practice.

PMID- 30204144
TI  - Imaging of large coronary fistula using echocardiography.
AB  - Coronary fistulas are defined as the presence of an abnormal connection between
      the coronary arteries and the low-pressure vascular area or the cardiac cavity.
      The clinical significance depends on the amount of blood flow through the fistula
      segment, the volumetric load on the right and left heart chambers, and whether it
      leads to a coronary steal phenomenon. Although fistula flow can be better
      visualized by angiographic methods, it can also be seen by echocardiography. In
      this case, the fistula flow draining to the left ventricle was demonstratively
      visualized.

PMID- 30204145
TI  - Case Image: Late detachment of an Amplatzer septal occluder device.

PMID- 30204146
TI  - Case Image: An unusual cause of dyspnea: Spontaneous pneumopericardium.

PMID- 30204147
TI  - Case Image: Multimodality imaging and histopathological diagnosis of an insidious
      enemy: cardiac metastasis of malignant melanoma with unknown primary origin.

PMID- 30204148
TI  - Case Image: Successful endovascular treatment of a giant left subclavian artery
      pseudoaneurysm causing severe dyspnea.

PMID- 30204149
TI  - Treatment of superficial incisional infection.

PMID- 30204150
TI  - Authors reply.

PMID- 30204151
TI  - No-touch method: New devices need new approaches.

PMID- 30204152
TI  - Whole genome sequencing data for two individuals of Pakistani descent.
AB  - Here we report next-generation based whole genome sequencing of two individuals
      (H1 and H2) from a family of Pakistani descent. The genomic DNA was used to
      prepare paired-end libraries for whole-genome sequencing. Deep sequencing yielded
      706.49 and 778.12 million mapped reads corresponding to 70.64 and 77.81 Gb
      sequence data and 23* and 25* average coverage for H1 and H2, respectively.
      Notably, a total of 448,544 and 470,683 novel variants, not present in the single
      nucleotide polymorphism database (dbSNP), were identified in H1 and H2,
      respectively. Comparative analysis identified 2,415,852 variants common in both
      genomes including 240,181 variants absent in the dbSNP. Principal component
      analysis linked the ancestry of both genomes with South Asian populations. In
      conclusion, we report whole genome sequences of two individuals from a family of
      Pakistani descent.

PMID- 30204153
TI  - Single-cell RNA sequencing of adult mouse testes.
AB  - Spermatogenesis is an efficient and complex system of continuous cell
      differentiation. Previous studies investigating the transcriptomes of different
      cell populations in the testis relied either on sorting cells, cell depletion, or
      juvenile animals where not all stages of spermatogenesis have been completed. We
      present single-cell RNA sequencing (scRNA-Seq) data of 2,500 cells from the
      testes of two 8-week-old C57Bl/6J mice. Our dataset includes all spermatogenic
      stages from preleptotene to condensing spermatids as well as individual
      spermatogonia, Sertoli and Leydig cells. The data capture the full continuity of
      the meiotic and postmeiotic stages of spermatogenesis, and is thus ideally suited
      for marker discovery, network inference and similar analyses for which temporal
      ordering of differentiation processes can be exploited. Furthermore, it can serve
      as a reference for future studies involving single-cell RNA-Seq in mice where
      spermatogenesis is perturbed.

PMID- 30204154
TI  - The eICU Collaborative Research Database, a freely available multi-center
      database for critical care research.
AB  - Critical care patients are monitored closely through the course of their illness.
      As a result of this monitoring, large amounts of data are routinely collected for
      these patients. Philips Healthcare has developed a telehealth system, the eICU
      Program, which leverages these data to support management of critically ill
      patients. Here we describe the eICU Collaborative Research Database, a multi
      center intensive care unit (ICU)database with high granularity data for over
      200,000 admissions to ICUs monitored by eICU Programs across the United States.
      The database is deidentified, and includes vital sign measurements, care plan
      documentation, severity of illness measures, diagnosis information, treatment
      information, and more. Data are publicly available after registration, including
      completion of a training course in research with human subjects and signing of a
      data use agreement mandating responsible handling of the data and adhering to the
      principle of collaborative research. The freely available nature of the data will
      support a number of applications including the development of machine learning
      algorithms, decision support tools, and clinical research.

PMID- 30204155
TI  - Seafloor crustal deformation data along the subduction zones around Japan
      obtained by GNSS-A observations.
AB  - Crustal deformation data obtained by geodetic observation networks are
      foundations in the fields of geodesy and seismology. These data are essential for
      understanding plate motion and earthquake sources and for simulating earthquake
      and tsunami scenarios. Although relatively scarce, seafloor geodetic data are
      particularly important for monitoring the behaviour of undersea interplate
      boundary regions. Since the mid-1990s, we have been developing the combined
      Global Navigation Satellite System-Acoustic ranging (GNSS-A) technique for
      realizing seafloor geodesy. This technique allows us to collect time series of
      seafloor crustal deformation. Our published data can be used to investigate
      several seismological phenomena along the subduction zones around Japan, namely
      the Nankai Trough, Sagami Trough and Japan Trench. These regions are globally
      important places in geodesy and seismology and are also suitable for comparison
      with other geophysical datasets. Our intention is for these data to promote
      further understanding of megathrust zones.

PMID- 30204157
TI  - Ultrasound-induced gelation of a giant macrocycle.
AB  - A 68-membered macrocycle undergoes ultrasound-induced supramolecular gelation in
      acetonitrile. The sonogel shows a remarkable thermostability, indicating that
      self-assembly is mediated by exceptionally robust non-covalent interactions.
      Model compounds indicate that the macrocyclic topology is essential for gelation
      to occur.

PMID- 30204158
TI  - CDy14: a novel biofilm probe targeting exopolysaccharide Psl.
AB  - Detection of biofilm bacteria would be an ideal method for the physicians to
      diagnose chronic bacterial infections directly, but there are few imaging probes
      available so far. Here, we report the development of a novel biofilm detecting
      fluorescent probe, CDy14, through an unbiased screening of a fluorescence library
      and elucidated its binding partner Psl, an exopolysaccharide of the biofilm.

PMID- 30204159
TI  - Constructing POSS and viologen-linked porous cationic frameworks induced by the
      Zincke reaction for efficient CO2 capture and conversion.
AB  - POSS and viologen-linked porous cationic frameworks (V-PCIF-X, X = Cl, Br) are
      constructed via the Zincke reaction between octa(aminophenyl)silsesquioxane and
      viologen linkers. The typical V-PCIF-Br has a high surface area with abundant
      ionic sites, micro-/mesopores and Si-OH groups, serving as an efficient porous
      adsorbent and metal-free catalyst for simultaneous CO2 capture and conversion.

PMID- 30204156
TI  - The Mount Sinai cohort of large-scale genomic, transcriptomic and proteomic data
      in Alzheimer's disease.
AB  - Alzheimer's disease (AD) affects half the US population over the age of 85 and is
      universally fatal following an average course of 10 years of progressive
      cognitive disability. Genetic and genome-wide association studies (GWAS) have
      identified about 33 risk factor genes for common, late-onset AD (LOAD), but these
      risk loci fail to account for the majority of affected cases and can neither
      provide clinically meaningful prediction of development of AD nor offer
      actionable mechanisms. This cohort study generated large-scale matched multi
      Omics data in AD and control brains for exploring novel molecular underpinnings
      of AD. Specifically, we generated whole genome sequencing, whole exome
      sequencing, transcriptome sequencing and proteome profiling data from multiple
      regions of 364 postmortem control, mild cognitive impaired (MCI) and AD brains
      with rich clinical and pathophysiological data. All the data went through
      rigorous quality control. Both the raw and processed data are publicly available
      through the Synapse software platform.

PMID- 30204160
TI  - Structural analysis reveals the formation and role of RNA G-quadruplex structures
      in human mature microRNAs.
AB  - Here we identify hundreds of RNA G-quadruplex (rG4) candidates in microRNAs
      (miRNAs), characterize the miRNA structure and miRNA-mRNA interactions on several
      mammalian-conserved miRNAs, and reveal the formation of rG4s in miRNAs. Notably,
      we study the effect of these rG4s in cells and uncover the role of rG4s in miRNA
      mediated post-transcriptional regulation.

PMID- 30204162
TI  - Stereo-selectivity switchable ROP of rac-beta-butyrolactone initiated by salan
      ligated rare-earth metal amide complexes: the key role of the substituents on
      ligand frameworks.
AB  - A series of novel salan-ligated rare-earth metal amide complexes were prepared
      and employed as initiators for the ROP of rac-beta-butyrolactone (rac-BBL).
      Tuning the substituents on the N atoms of the ligand frameworks from aromatic
      groups to aliphatic groups results in switching tacticity from iso-tactic to
      syndio-tactic in rac-BBL polymerization.

PMID- 30204161
TI  - Rotational and translational diffusion of size-dependent fluorescent probes in
      homogeneous and heterogeneous environments.
AB  - Living cells are crowded with dynamic distributions of macromolecules and
      organelles that influence protein diffusion, molecular transport, biochemical
      reactions, and protein assembly. Here, we test the hypothesis that the diffusion
      of single molecules deviates from Brownian motion as described by the Stokes
      Einstein model in a manner that depends on the viscosity range, the chemical
      structure of both the diffusing species and the crowding agents, and the spatio
      temporal resolution of the employed analytical methods. Our size-dependent
      fluorescent probes are rhodamine-110, quantum dots, enhanced green fluorescent
      proteins (EGFP), and mCerulean3-linker-mCitrine FRET probes with various linker
      length and flexibility. Using fluorescence correlation spectroscopy (FCS), we
      investigated the translational diffusion of structure-dependent fluorescent
      probes, at the single-molecule level, in homogeneous (glycerol) and heterogeneous
      (Ficoll-70) solutions as a function of the bulk viscosity. Complementary
      rotational diffusion studies using time-resolved anisotropy enable us to assess
      weak interactions in crowded and viscous environments. Overall, our results show
      negative deviation from the Stokes-Einstein model in a fluorophore- and
      environment-dependent manner. In addition, the deviation between the FCS-measured
      hydrodynamic radius of the FRET probes in a buffer at room temperature and the
      molecular-weight based estimate (Perrin equation) as the number of the amino acid
      residues in the linker increases. These studies are essential for quantitative
      biophysics using fluorescence- and diffusion-based studies of protein-protein
      interactions and biomolecular transport in living cells.

PMID- 30204163
TI  - Diving-floating locomotion induced by capturing and manipulating bubbles in an
      aqueous environment.
AB  - A superhydrophobic and superaerophilic surface was fabricated by facile self
      assembly of silica nanoparticle/PDMS composites. The relevant superaerophilic
      surface showed excellent adhesion to air bubbles in an aqueous environment. With
      bubbles adhering to the superaerophilic surface, the density of the whole system
      was adjustable, which was applied to induce a diving-floating locomotion in an
      aqueous environment.

PMID- 30204164
TI  - Synthesis and evaluation of pyrazine and quinoxaline fluorophores for in vivo
      detection of cerebral tau tangles in Alzheimer's models.
AB  - A series of pyrazine and quinoxaline probes (QNNs) were synthesized and
      evaluated. The quinoxaline derivative 3b, with high affinity and selectivity for
      tau aggregates, favorable fluorescence turn-on capability and brain kinetics, was
      successfully applied to the detection of tau tangles both in vitro and in mice in
      vivo.

PMID- 30204165
TI  - Synthesis of phthalic acid derivatives via Pd-catalyzed alkoxycarbonylation of
      aromatic C-H bonds with alkyl chloroformates.
AB  - A Pd(ii)-catalyzed alkoxycarbonylation of aromatic C-H bonds with alkyl
      chloroformates has been developed. A broad range of benzamides and alkyl
      chloroformates are compatible with this protocol. The reaction is operationally
      simple and scalable. The direct group could be readily removed to access
      substituted phthalic acid esters (PAEs), 1,2-dibenzyl alcohols and phthalamides.
      Besides alkoxycarbonylation of benzamide beta-C-H bonds, gamma
      alkoxycarbonylation of 2-phenylacetamide is also feasible.

PMID- 30204167
TI  - Triazole-bearing calixpyrroles: strong halide binding affinities through multiple
      N-H and C-H hydrogen bonds.
AB  - Triazole-bearing calixpyrroles (TCPs) were synthesized as artificial anion
      binding receptors. The additional C-HX hydrogen bonding interaction induced
      strong binding affinity towards halide ions. Using this strong binding affinity,
      Cl- was successfully extracted from the aqueous to organic phase.

PMID- 30204166
TI  - A new C,N-cyclometalated osmium(ii) arene anticancer scaffold with a handle for
      functionalization and antioxidative properties.
AB  - A series of six osmium(ii) complexes of the type [(eta6-p-cymene)Os(C^N)X] (X =
      chlorido or acetato) containing benzimidazole C^N ligands with an ester group as
      a handle for further functionalization have been synthesized. They exhibit IC50
      values in the low micromolar range in a panel of cisplatin (CDDP)-resistant
      cancer cells (approximately 10* more cytotoxic than CDDP in MCF-7), decrease the
      levels of intracellular ROS and reduce the NAD+ coenzyme, and inhibit tubulin
      polymerization. This discovery could open the door to a new large family of
      osmium(ii)-based bioconjugates with diverse modes of action.

PMID- 30204168
TI  - Entwined dimer formation from self-complementary bis-acridiniums.
AB  - A dicationic tweezer incorporating two acridinium moieties linked by a 2,6
      diphenylpyridine spacer was shown to self-assemble in an entwined dimer both in
      acetonitrile and water. The reaction was studied according to solvent polarity,
      temperature and concentration conditions. The entwined structure was confirmed in
      the solid state via single-crystal X-ray diffraction.

PMID- 30204169
TI  - Gold-catalyzed annulations of N-aryl ynamides with benzisoxazoles to construct 6H
      indolo[2,3-b]quinoline cores.
AB  - This work reports new annulations of N-aryl ynamides with benzisoxazoles to form
      6H-indolo[2,3-b]quinoline derivatives. The synthetic utility of this new method
      is manifested by its applicability to access naturally occurring alkaloids
      including norcryptotackeine, neocryptolepine and 11-methylneocryptol-epine. Our
      experimental data indicate that high-temperature conditions allow N-aryl
      nucleophiles to become conformationally flexible, rendering the attack at gold
      carbenes effective to generate reactive indoles that attack again the
      benzaldehyde to furnish the observed products.

PMID- 30204170
TI  - Solution-processed resistive switching memory devices based on hybrid organic
      inorganic materials and composites.
AB  - Resistive random-access memory (ReRAM) is expected to be the next-generation non
      volatile memory device because of its fast operation speed and low power
      consumption. Switching media in most ReMAM are oxides which are rigid and require
      high-temperature processing. Here, we review two emerging types of low-cost
      solution-processed ReRAMs with sandwich structures: one is hybrid nanocomposites
      with charge-trapping nanoparticles (NPs) embedded in a polymer matrix, and the
      other is hybrid halide perovskites which have been intensively investigated
      recently for optoelectronic applications. We will review the recent developments
      in materials selection, device performance and operation mechanisms. Resistive
      switching in hybrid materials and composites is ubiquitous because of the
      abundant existence of charge-trapping defects and interfaces. The future
      challenges and potential breakthroughs will also be outlined.

PMID- 30204171
TI  - Conformational restraint as a strategy for navigating towards lysosomes.
AB  - Using the conformational restraint strategy, we developed a hydrazonate-derived
      coumarin into a lysosome targeting probe for imaging native formaldehyde at the
      subcellular level. Using this probe, we observed the overproduction of
      formaldehyde in lysosomes when cells were treated with endoplasmic reticulum (ER)
      stress inducers, suggesting the involvement of formaldehyde in protein
      misfolding.

PMID- 30204172
TI  - A thermodynamically consistent phase diagram of a trimorphic pharmaceutical, l
      tyrosine ethyl ester, based on limited experimental data.
AB  - Crystalline polymorphs possess different physical properties, and phase changes
      between those polymorphs may affect the properties of engineered materials such
      as drugs. This is very well illustrated by the large effort that is put into the
      capability to predict phase behaviour of pharmaceuticals to avoid the unexpected
      appearance of different crystal forms. Much progress has been made, but one of
      the remaining challenges is (the accuracy in) the prediction of phase behaviour
      as a function of temperature. Obviously, predictions should at a certain point be
      verified against experimental data; however, it may not always be easy to
      elucidate the phase behaviour of a given compound experimentally, because
      thermodynamically and kinetically controlled phenomena occur in a convoluted
      fashion in experimental data. The present paper discusses the trimorphism of l
      tyrosine ethyl ester as an example case of how experimental data in combination
      with the thermodynamic tenets lead to a consistent phase diagram, which can be
      used as the basis for pharmaceutical formulations and for comparison with
      polymorph predictions by computer. The positions of the two-phase equilibria I
      II, I-III, and I-L have been obtained experimentally. Using the Clapeyron
      equation and the alternation rule, it has been shown how the positions of the
      other equilibria II-L, III-L, and II-III can be deduced in combination with the
      stability rankings of the phases and the phase equilibria. The experimental data
      have been obtained by synchrotron X-ray diffraction, Raman spectroscopy, and
      thermal analysis as a function of pressure and temperature. Furthermore,
      laboratory X-ray diffraction as a function of temperature and differential
      scanning calorimetry have been used. At room temperature, form II is the most
      stable phase, which remains stable with increasing pressure, as it possesses the
      smallest specific volume. Form I becomes stable above 33  degrees C (306 K), but
      with increasing pressure it turns into form III. On thermodynamic grounds, form
      III is expected to have a stable domain at very low temperatures.

PMID- 30204173
TI  - Reaction mechanism of the selective reduction of CO2 to CO by a tetraaza
      [CoIIN4H]2+ complex in the presence of protons.
AB  - The tetraaza [CoIIN4H]2+ complex (1) is remarkable for its ability to selectively
      reduce CO2 to CO with 45% Faradaic efficiency and a CO to H2 ratio of 3 : 2. We
      employ density functional theory (DFT) to determine the reasons behind the
      unusual catalytic properties of 1 and the most likely mechanism for CO2
      reduction. The selectivity for CO2 over proton reduction is explained by
      analyzing the catalyst's affinity for the possible ligands present under typical
      reaction conditions: acetonitrile, water, CO2, and bicarbonate. After reduction
      of the catalyst by two electrons, formation of [CoIN4H]+-CO2- is strongly
      favored. Based on thermodynamic and kinetic data, we establish that the only
      likely route for producing CO from here consists of a protonation step to yield
      [CoIN4H]+-CO2H, followed by reaction with CO2 to form [CoIIN4H]2+-CO and
      bicarbonate. This conclusion corroborates the idea of a direct role of CO2 as a
      Lewis acid to assist in C-O bond dissociation, a conjecture put forward by other
      authors to explain recent experimental observations. The pathway to formic acid
      is predicted to be forbidden by high activation barriers, in accordance with the
      products that are known to be generated by 1. Calculated physical observables
      such as standard reduction potentials and the turnover frequency for our proposed
      catalytic cycle are in agreement with available experimental data reported in the
      literature. The mechanism also makes a prediction that may be experimentally
      verified: that the rate of CO formation should increase linearly with the partial
      pressure of CO2.

PMID- 30204174
TI  - A comparative DFT study of TBD-catalyzed reactions of amines with CO2 and
      hydrosilane: the effect of solvent polarity on the mechanistic preference and the
      origins of chemoselectivities.
AB  - A DFT comparative mechanistic study unveils that the TBD-catalyzed reactions of
      amines with CO2 and hydrosilanes may either undergo a neutral mechanism or a
      mechanism involving free ions, depending on the polarity of the solvent. The
      nucleophilicity of the amines is an important factor to determine the
      chemoselectivities of the reactions to give formamide or aminal/N-methylated
      amine.

PMID- 30204175
TI  - Evaluation of cigarette flavoring quality via surface-enhanced Raman
      spectroscopy.
AB  - Herein, surface-enhanced Raman spectroscopy (SERS) combined with principal
      component analysis (PCA) has been successfully applied in the evaluation of
      cigarette flavoring quality using monolayer films of Au nanoparticles as
      substrates. With such a method, even a slight difference in the formula of the
      essence that cannot be directly identified by SERS can be distinguished.

PMID- 30204176
TI  - Correction: A tumor-targeting probe based on a mitophagy process for live
      imaging.
AB  - Correction for 'A tumor-targeting probe based on a mitophagy process for live
      imaging' by Lijuan Gui et al., Chem. Commun., 2018, 54, 9675-9678.

PMID- 30204177
TI  - Hybrid nanoparticles for magnetic and plasmonic hyperthermia.
AB  - The present manuscript reports the use of hybrid magneto-plasmonic nanoparticles
      (HMPNPs) based on iron oxide nanoparticles and Au nanorods as colloidal
      nanoheaters. The individual synthesis of the magnetic and plasmonic components
      allowed optimizing their features for heating performance separately, before they
      were hybridized. Besides, a detailed characterization and finite element
      simulations were carried out to explain the interaction effects observed between
      the phases of the HMPNPs. The study also analyzed the heating power of these
      nanostructures when they were excited with infrared light and AC magnetic fields,
      and compared this with the heating power of their plasmonic and magnetic
      components. In the latter case, the AC magnetization curves revealed that the
      magnetic dipolar interactions increase the amount of heat released by the hybrid
      nanostructures.

PMID- 30204178
TI  - Estimation of diffusive states from single-particle trajectory in heterogeneous
      medium using machine-learning methods.
AB  - We propose a novel approach to analyze random walks in heterogeneous medium using
      a hybrid machine-learning method based on a gamma mixture and a hidden Markov
      model. A gamma mixture and a hidden Markov model respectively provide the number
      and the most probable sequence of diffusive states from the time series position
      data of particles/molecules obtained by single-particle/molecule tracking
      (SPT/SMT) method. We evaluate the performance of our proposed method for
      numerically generated trajectories. It is shown that our proposed method can
      correctly extract the number of diffusive states when each trajectory is long
      enough to be frame averaged. We also indicate that our method can provide an
      indicator whether the assumption of a medium consisting of discrete diffusive
      states is appropriate or not based on the available amount of trajectory data.
      Then, we demonstrate an application of our method to the analysis of
      experimentally obtained SPT data.

PMID- 30204179
TI  - Influence of crystallographic environment on scandium K-edge X-ray absorption
      near-edge structure spectra.
AB  - The absence of an extensive series of Sc K-edge X-ray absorption near-edge
      structure spectroscopy (XANES) reference spectra and the scarcity of direct
      structural data on Sc are major hurdles to develop our understanding of Sc
      chemistry. However, this first step is essential to develop new Sc-based
      applications and to better understand the formation of Sc deposits. Here, we
      present a detailed comparative study of Sc K-edge XANES spectra of three Sc
      bearing compounds: a garnet (Ca3Sc2Si3O12), an oxide (Sc2O3) and a phosphate
      (ScPO4.2H2O). First-principles calculations have been performed to interpret the
      origin of the K pre-edge spectral features. We demonstrate the validity of our
      approach by reproducing satisfyingly the experimental spectra. The densities of
      states projected on the absorbing Sc atom and its first neighbours give the
      possibility to interpret the position and intensity of the pre-edge XANES
      features in terms of Sc local environment. The pre-edge features provide
      information on p-d mixing of the absorber orbitals giving clues on the
      centrosymmetry of the site and on the mixing of the empty 4p orbitals of the
      absorber with empty 3d orbitals of the neighbours via the empty p orbitals of the
      ligands. We also show that these features give a first estimate of the crystal
      field splitting energy (ca. 1.5 eV), inaccessible using other spectroscopic
      methods. Comparisons with K-edge spectra of other 3d0 ions from the literature
      reveal the specificities of the Sc pre-edge, indicating that core-hole screening
      is weaker than for Ti4+-bearing compounds. This study provides a dataset of
      spectral signatures and a theoretical basis for their interpretation, a
      requirement for future studies on Sc chemical form in synthetic and natural
      systems.

PMID- 30204180
TI  - Theoretical insight into joint photodynamic action of a gold(i) complex and a
      BODIPY chromophore for singlet oxygen generation.
AB  - Density functional theory is herein employed to provide theoretical insight into
      the mechanism involved in 1O2 photosensitization by a gold-BODIPY combined
      complex proposed as a promising photodynamic therapy agent. The protocol is thus
      used to compute the non-radiative rate constants for the S1 -> Tj intersystem
      crossing transitions. Calculations show that while the incorporation of an iodine
      atom into the core skeleton of BODIPY enhances the singlet-triplet intersystem
      crossing (ISC) efficiency due to the occurrence of the singlet-triplet transition
      between states with different orbital characters (pipi* -> pin*), the presence of
      a gold atom, even if not directly anchored to the chromophore core but through a
      triplet bond, equally entails an increase of the spin-orbit coupling constant due
      to the heavy atom effect. In this way, the system is able to generate singlet
      molecular oxygen, the key cytotoxic agent in PDT. Our results fit well with the
      experimental singlet oxygen quantum yield and cytotoxicity determination.

PMID- 30204181
TI  - Tunable interlayer coupling and Schottky barrier in graphene and Janus MoSSe
      heterostructures by applying an external field.
AB  - A Janus MoSSe monolayer, synthesized recently though the chemical vapor
      deposition method [A. Y. Lu, H. Zhu, J. Xiao, C. P. Chuu, Y. Han, M. H. Chiu, C.
      C. Cheng, C. W. Yang, K. H. Wei Y. Yang, Y. Wang, D. Sokaras, D. Nordlund, P.
      Yang, D. A. Muller, M. Y. Chou, X. Zhang and L. J. Li, Nat. Nanotechnol., 2017,
      12, 744-749], has drawn considerable attention as a new two-dimensional (2D)
      material owing to its fascinating electronic and optical properties. In this
      study, based on first-principles calculations, we systematically explore for the
      first time the performance of Janus MoSSe monolayers as a channel material
      contacting with graphene to form van der Waals (vdW) heterostructures. Our
      calculations show that the intrinsic electronic properties of both the graphene
      and MoSSe monolayer are preserved well in our proposed two graphene/MoSSe
      heterostructures (i.e. G/SMoSe and G/SeMoS heterostructures), and n-type Schottky
      contacts with a small Schottky barrier height (SBH) are formed at their
      respective interfaces. An analytical model is presented for the barrier heights.
      Moreover, the n-type Schottky barrier at the G/SMoSe heterostructure interface
      can be reduced by increasing the interlayer distance and can even be changed to
      an Ohmic contact by applying a negative electric field. More interestingly,
      varying the interlayer distance or applying an external electric field can
      effectively modulate the Schottky barrier and the Schottky contact (n-type and p
      type) of the G/SeMoS heterostructure interface. These theoretical findings not
      only provide insights into the fundamental properties of the graphene/MoSSe
      interfaces but also open the possibility of designing high-performance field
      effect transistors (FETs) based on the graphene/MoSSe heterostructures.

PMID- 30204182
TI  - Kinetics of the defunctionalization of oxidized few-layer graphene nanoflakes.
AB  - Thermal defunctionalization of oxidized jellyfish-like few-layer graphene
      nanoflakes was studied under non-isothermal conditions by simultaneous thermal
      analysis. Activation energies for thermal decomposition of different oxygen
      functional groups were calculated by the Kissinger method and compared with those
      for oxidized carbon nanotubes. Oxygen content in graphene nanoflakes was found to
      significantly affect the decomposition activation energies of carboxylic and
      keto/hydroxy acids because of their acceptor properties and strong distortion of
      the graphene layers at the edges of the nanoflakes. The structure of the carbon
      material and the oxygen chemical state significantly influence the decomposition
      kinetics of thermally stable oxygen-containing groups. The activation energy for
      thermal decomposition of phenol groups (110-150 kJ mol-1) is close to that for
      graphene oxide reduction.

PMID- 30204183
TI  - Near-field depolarization of tip-enhanced Raman scattering by single azo
      chromophores.
AB  - The intrinsic symmetry and orientation of single molecules play a crucial role in
      enhanced optical spectroscopy and nanoscopic imaging. Unlike bulk materials, in
      which all molecular orientations are unavoidably averaged in the far-field,
      intensities of vibrational modes in tip-enhanced Raman scattering (TERS) depend
      greatly on the polarization direction of near-field light. It means that a near
      field Raman "dichroism" becomes possible for anisotropic single molecules.
      Quantitative evaluation of the molecular orientation gets complicated by the
      depolarization of TERS intensities. Clearly, the depolarization effect is
      enhanced with an optical antenna and/or a substrate due to their anisotropic
      origin. In this study, we provide theoretical and experimental insights into
      Raman tensors of a single azobenzene chromophore, a Disperse Orange 3 (DO3)
      molecule, supported with a glass base. It is shown that the Raman intensities of
      the spectral bands corresponding to symmetric and antisymmetric vibrations of the
      DO3 molecule, for example, -NO2 and -NH2 moieties, behave differently on the
      nanoscale. In particular, three-dimensional far- and near-field Raman diagrams
      indicate that antisymmetric vibrations become highly depolarized, whereas
      symmetric vibrations remain unchangeable but intensities of their spectral bands
      are enhanced. Here, we introduce a near-field depolarization factor defined as a
      normalized discrepancy of longitudinal and transverse TERS signals. We believe
      that our first steps will ultimately lead to advanced facilities of TERS
      spectroscopy and nanoscopy, related to the orientation of anisotropic single
      molecules and their symmetries.

PMID- 30204184
TI  - Towards operando computational modeling in heterogeneous catalysis.
AB  - An increased synergy between experimental and theoretical investigations in
      heterogeneous catalysis has become apparent during the last decade. Experimental
      work has extended from ultra-high vacuum and low temperature towards operando
      conditions. These developments have motivated the computational community to move
      from standard descriptive computational models, based on inspection of the
      potential energy surface at 0 K and low reactant concentrations (0 K/UHV model),
      to more realistic conditions. The transition from 0 K/UHV to operando models has
      been backed by significant developments in computer hardware and software over
      the past few decades. New methodological developments, designed to overcome part
      of the gap between 0 K/UHV and operando conditions, include (i) global
      optimization techniques, (ii) ab initio constrained thermodynamics, (iii) biased
      molecular dynamics, (iv) microkinetic models of reaction networks and (v) machine
      learning approaches. The importance of the transition is highlighted by
      discussing how the molecular level picture of catalytic sites and the associated
      reaction mechanisms changes when the chemical environment, pressure and
      temperature effects are correctly accounted for in molecular simulations. It is
      the purpose of this review to discuss each method on an equal footing, and to
      draw connections between methods, particularly where they may be applied in
      combination.

PMID- 30204185
TI  - Designing a facile low cost synthesis strategy for the Na-V-S-O systems,
      NaV(SO4)2, Na3V(SO4)3 and Na2VO(SO4)2.
AB  - Alkali metal transition metal sulfates have attracted considerable interest as
      potential electrodes for Na ion battery materials. While there has been
      significant research on Fe based systems, research on V based systems has been
      lacking, apart from a recent report on Na2VO(SO4)2. This can be related to the
      complex synthetic routes previously reported to make sodium vanadium sulfate
      systems. In this paper, we report a simple route towards the synthesis of three
      such sodium vanadium sulfate systems, NaV(SO4)2, Na2VO(SO4)2, and Na3V(SO4)3. We
      analyse the resulting products through X-ray diffraction and Raman spectroscopy
      to highlight the formation of high quality samples via this simple solution
      route, with subsequent low temperature (<400  degrees C) heat treatment. This
      facile new route will allow these materials to be considered for future
      applications rather than as simply chemical curiosities.

PMID- 30204186
TI  - Acridine-decorated cyclometallated gold(iii) complexes: synthesis and anti-tumour
      investigations.
AB  - (C^N) and (C^N^C) cyclometalated Au(iii) represent a highly promising class of
      potential anticancer agents. We report here the synthesis of seven new
      cyclometalated Au(iii) complexes with five of them bearing an acridine moiety
      attached via (N^O) or (N^N) chelates, acyclic amino carbenes (AAC) and N
      heterocyclic carbenes (NHC). The antiproliferative properties of the different
      complexes were evaluated in vitro on a panel of cancer cells including leukaemia,
      lung and breast cancer cells. We observed a trend between the cytotoxicity and
      the intracellular gold uptake of some representative compounds of the series.
      Some of the acridine-decorated complexes were demonstrated to interact with ds
      DNA using FRET-melting techniques.

PMID- 30204191
TI  - Millifluidic culture improves human midbrain organoid vitality and
      differentiation.
AB  - Human midbrain-specific organoids (hMOs) serve as an experimental in vitro model
      for studying the pathogenesis of Parkinson's disease (PD). In hMOs,
      neuroepithelial stem cells (NESCs) give rise to functional midbrain dopaminergic
      (mDA) neurons that are selectively degenerating during PD. A limitation of the
      hMO model is an under-supply of oxygen and nutrients to the densely packed core
      region, which leads eventually to a "dead core". To reduce this phenomenon, we
      applied a millifluidic culture system that ensures media supply by continuous
      laminar flow. We developed a computational model of oxygen transport and
      consumption in order to predict oxygen levels within the hMOs. The modelling
      predicts higher oxygen levels in the hMO core region under millifluidic
      conditions. In agreement with the computational model, a significantly smaller
      "dead core" was observed in hMOs cultured in a bioreactor system compared to
      those ones kept under conventional shaking conditions. Comparing the necrotic
      core regions in the organoids with those obtained from the model allowed an
      estimation of the critical oxygen concentration necessary for ensuring cell
      vitality. Besides the reduced "dead core" size, the differentiation efficiency
      from NESCs to mDA neurons was elevated in hMOs exposed to medium flow. Increased
      differentiation involved a metabolic maturation process that was further
      developed in the millifluidic culture. Overall, bioreactor conditions that
      improve hMO quality are worth considering in the context of advanced PD
      modelling.

PMID- 30204192
TI  - Fibrous strain sensor with ultra-sensitivity, wide sensing range, and large
      linearity for full-range detection of human motion.
AB  - It is challenging to construct exquisite microstructures for integrating
      extraordinary sensitivity, wide strain range detectability, low hysteresis, good
      linearity, and excellent reliability and stability in a single type of strain
      sensor. In this paper, we report a high-performance fibrous strain sensor with
      ultrahigh sensitivity (gauge factor up to 350), wide sensing range (0.1% to 150%
      strain), low hysteresis, good linearity over a large strain range (up to 50%),
      and excellent reliability and stability (>2000 cycles). Our fibrous strain sensor
      exhibits superior comprehensive properties to previous strain sensors, attributed
      to its hierarchical microstructure composed of twisted polyurethane fibers and
      microcracked poly(3,4-ethylenedioxythiophene):poly(4-styrenesulfonate) sensing
      layer on each fiber, bridged by carbon nanotube agglomerates. This sensor is
      attractive and promising for the full-range detection of human motion from subtle
      deformations to large movements. In addition, the spatial extensional strain
      distribution of human skin can also be detected by the sensing fabric woven by
      this fibrous sensor due to its knittability.

PMID- 30204194
TI  - Open multi-culture platform for simple and flexible study of multi-cell type
      interactions.
AB  - The study of multi-cell-type (MCT) interactions has the potential to
      significantly impact our understanding of tissue and disease biology. Such
      studies require innovative culture tools for unraveling the contributions of each
      cell type. Micro- and macro-scale platforms for MCT culture each have different
      advantages and disadvantages owing to their widely different capabilities,
      availability, and ease-of-use. However, as evidenced in the literature, there are
      very few examples of MCT studies and culture platforms, suggesting both
      biological and technical barriers. We have developed an open multi-culture
      platform to promote more rapid progress by integrating advantages of both micro-
      and macro-scale culture devices. The proposed open multi-culture platform
      addresses technical barriers by allowing easy customization, independent control
      of basic physical culture parameters, and incorporation of multiple culture
      modalities (e.g., 2D, 3D, transwell, and spheroid). The design also permits the
      user to obtain independent endpoints for each culture region. We demonstrate use
      of the platform in two example studies where we evaluated how cell ratio and cell
      types influence the response of triple negative breast cancer cells to heat
      damage and Hedgehog signaling. We also show that the platform can improve soluble
      factor transport between cell types compared to compartmentalized macro- and
      micro-scale alternatives. Last, we examine current and future challenges of the
      platform. We envision simple, yet flexible and customizable, platforms such as
      this will be important for advancing in vitro study of tissue and tumor biology.

PMID- 30204195
TI  - Bio-cleavable nanoprobes for target-triggered catalytic hairpin assembly
      amplification detection of microRNAs in live cancer cells.
AB  - The monitoring and imaging of intracellular microRNAs (miRNAs) with specific
      sequences plays a vital role in cell biology as it can potentially elucidate many
      cellular processes and diseases related to miRNAs in living cells with accurate
      information. However, the detection of trace amounts of under-expressed
      intracellular miRNAs in living cells represents one of the current major
      challenges. In an effort to address this issue, we describe the establishment of
      an in cell catalytic hairpin assembly (CHA) signal amplification strategy for
      imaging under-expressed intracellular miRNAs in this work. Gold nanoparticles
      functionalized with FAM- and TAMRA-labeled hairpins with disulfide bonds in the
      stems are readily delivered into cells via endocytosis. Glutathione with
      evaluated concentrations in cancer cells cleaves the disulfide bonds in the
      hairpins by reduction to release the hairpins, and the target miRNAs further
      trigger CHA between the two hairpins to form many DNA duplexes, which bring the
      FAM and TAMRA labels into close proximity to generate apparently enhanced
      fluorescence resonance energy transfer (FRET) for the sensitive monitoring of low
      amounts of under-expressed miRNAs in live cancer cells. Using CHA to amplify the
      signal output and FRET to reduce the background noise, a significantly enhanced
      signal-to-noise ratio, thereby high sensitivity, over conventional fluorescence
      imaging can be realized, making our method particularly suitable for monitoring
      low levels of intracellular species.

PMID- 30204196
TI  - Stereoselective synthesis of sugar-fused (or 1,2-annulated) isochromans and
      isochromanones by using oxa-Pictet-Spengler reaction.
AB  - A highly efficient stereoselective synthesis of sugar fused 1,2-annulated
      isochromans is reported by utilizing the oxa-Pictet-Spengler cyclization
      reaction. The process is found to be very general as both glucal and galactal
      derived C2-hydroxy-alpha-C-aryl glycosides lead to the target molecules in good
      yields. The utility of this strategy was extended to the synthesis of sugar fused
      isochromanones, which are bergenin type molecules.

PMID- 30204197
TI  - High-quality and low-cost three-dimensional graphene from graphite flakes via
      carbocation-induced interlayer oxygen release.
AB  - Three-dimensional (3D) graphene can fully bring the excellent properties of
      graphene into wide utilization. However, its production requires the use of
      graphene oxide as the intermediate or harsh chemical vapour deposition
      conditions, which do not meet the requirements of high quality and low cost
      simultaneously. Herein, we report a room-temperature low-cost strategy to produce
      3D graphene under ambient conditions, which is achieved via carbocation-induced
      interlayer oxygen release. Graphite layers can transfer electrons to hydrogen
      peroxide, forming carbocations, which in turn oxidize hydrogen peroxide to
      release O2, substantially enlarging the interlayer space of graphite. We show
      that graphite can expand 1000 times or more into the liquid phase and no oxygen
      containing groups are introduced on the basal plane. The obtained 3D graphene has
      an open porous structure and a specific surface area (SSA) of 1245 m2 g-1, which
      is comparable to that of CVD-grown 3D graphene networks and equivalent to that of
      2-layer graphene. Moreover, the quality of 3D graphene is high, with ID/IG
      smaller than 0.2. The as-obtained 3D graphene can be easily exfoliated into
      graphene sheets with 100% yield. Gifted with well-maintained crystalline quality
      and highly accessible surface area, the 3D graphene-based composite exhibits
      ultra-long life when used as lithium anode, with slight capacity degradation
      after 1000 cycles.

PMID- 30204200
TI  - Chiral sensors for determining the absolute configurations of alpha-amino acid
      derivatives.
AB  - A simple strategy for configurational assignments of alpha-amino acids has been
      developed by comparison of the proton NMR chemical shift values of the alpha
      hydrogens of N-phthaloyl protected alpha-amino acids in the presence of (R)-CSA 1
      and (S)-CSA 1, respectively. Highly resolved NMR spectra can be obtained directly
      on the mixed solution of the chiral solvating agents with N-phthaloyl protected
      alpha-amino acids in NMR tubes, giving well distinguishable proton signals
      without interference which dramatically improve the accuracy of assignment and
      hasten the assigning procedure. The strategy is widely applicable for varied
      natural and non-natural amino acids.

PMID- 30204201
TI  - Giant resistive switching in mixed phase BiFeO3via phase population control.
AB  - Highly-strained coherent interfaces, between rhombohedral-like (R) and tetragonal
      like (T) phases in BiFeO3 thin films, often show enhanced electrical conductivity
      in comparison to non-interfacial regions. In principle, changing the population
      and distribution of these interfaces should therefore allow different resistance
      states to be created. However, doing this controllably has been challenging to
      date. Here, we show that local thin film phase microstructures (and hence R-T
      interface densities) can be changed in a thermodynamically predictable way
      (predictions made using atomistic simulations) by applying different combinations
      of mechanical stress and electric field. We use both pressure and electric field
      to reversibly generate metastable changes in microstructure that result in very
      large changes of resistance of up to 108%, comparable to those seen in Tunnelling
      Electro-Resistance (TER) devices.

PMID- 30204206
TI  - Few-layer bismuthene for ultrashort pulse generation in a dissipative system
      based on an evanescent field.
AB  - Bismuthene has attracted a great deal of attention because of its unique
      electronic and optical properties. However, there are few reported applications
      of bismuthene in nonlinear optical applications. In this research, a dissipative
      soliton ytterbium-doped mode-locked fiber laser at 1 MUm regime with a bismuthene
      saturable absorber (SA) by using evanescent field interaction for the first time
      is demonstrated. The nonlinear optical absorption of microfiber-based bismuthene
      SA is shown experimentally by using a homemade ultrafast fiber laser, whose
      saturation intensity and modulation depth are about 13 MW cm-2 and 2.2%,
      respectively. Relying on the excellent nonlinear optical property of the
      bismuthene SA, the typical dissipative solitons with a repetition rate of 21.74
      MHz are generated at a center wavelength of 1034.4 nm. The time-bandwidth product
      of the pulse is about 23.07 with a pulse width of 30.25 ps. The results
      demonstrate that bismuthene is a good candidate for application in a 1 MUm wave
      breaking-free mode-locked fiber laser and nonlinear photonic components.

PMID- 30204204
TI  - Synthesis of protectin D1 analogs: novel pro-resolution and radiotracer agents.
AB  - Protectin D1 is a specialized pro-resolving mediator with potent pro-resolving
      and anti-inflammatory effects in vivo in several human disease models. Herein the
      preparation of the first synthetic analog of protectin D1, named 22-F-PD1, is
      presented together with data from in vivo investigations. This analog showed
      potent pro-resolving and anti-inflammatory properties. These results inspired the
      preparation of the radiotracer 22-[18F]F-PD1-ME that was used in a positron
      emission tomography proof of concept study. Altogether, the findings presented
      contribute to new knowledge on the biomolecular properties of protectin D1
      analogs. In addition, an improved formal synthesis of the metabolite 22-OH-PD1 is
      reported.

PMID- 30204209
TI  - Intermediate crystalline structures of colloids in shape space.
AB  - We computationally study the thermodynamic assembly of more than 40 000 hard,
      convex polyhedra belonging to three families of shapes associated with the
      triangle groups 323, 423, and 523. Each family is defined by vertex and/or edge
      truncation of symmetric polyhedra with equal edge length, producing shapes for
      which the majority are intermediates of more symmetric polyhedra found among the
      Platonic, Archimedean, and Catalan solids. In addition to the complex crystals
      cI16 lithium, BC8 silicon, gamma-brass, beta-manganese, and a dodecagonal
      quasicrystal, we find that most intermediate shapes assemble distorted variants
      of four basic cubic crystals: face-centered cubic, body-centered cubic, simple
      cubic, and diamond. To quantify the degree of distortion, we developed an
      algorithm that extracts lattice vectors from particle positions and then
      evaluates closeness to the four reference cubic crystals. This analysis allows us
      to group together in shape space related intermediate structures that would
      otherwise be placed in different lattice systems had we followed the lattice
      systems' strict definitions for angles and lengths of lattice vectors. The
      resulting landscapes show, as a function of shape, regions where ordered
      structures assemble, what is assembled and at what density, locations of
      transitions between regions of ordered structures, and regions of disorder. Our
      results provide a guide to self-assembling a host of related colloidal crystals
      through systematic design, by careful tweaking of the particle shape.

PMID- 30204212
TI  - A segregative phase separation scenario of the formation of the bacterial
      nucleoid.
AB  - The mechanism responsible for the compaction of the genomic DNA of bacteria
      inside a structure called the nucleoid is a longstanding but still lively debated
      question. Most puzzling is the fact that the nucleoid occupies only a small
      fraction of the cell, although it is not separated from the rest of the cytoplasm
      by any membrane and would occupy a volume about a thousand times larger outside
      the cell. Here, by performing numerical simulations using coarse-grained models,
      we elaborate on the conjecture that the formation of the nucleoid may result from
      a segregative phase separation mechanism driven by the demixing of the DNA coil
      and non-binding globular macromolecules present in the cytoplasm, presumably
      functional ribosomes. Simulations performed with crowders having a spherical,
      dumbbell or octahedral geometry highlight the sensitive dependence of the level
      of DNA compaction on the dissymmetry of DNA/DNA, DNA/crowder, and crowder/crowder
      repulsive interactions, thereby supporting the segregative phase separation
      scenario. Simulations also consistently predict a much stronger DNA compaction
      close to the jamming threshold. Moreover, simulations performed with crowders of
      different sizes suggest that the final density distribution of each species
      results from the competition between thermodynamic forces and steric hindrance,
      so that bigger crowders are expelled selectively from the nucleoid only at
      moderate total crowder concentrations. This work leads to several predictions,
      which may eventually be tested experimentally.

PMID- 30204213
TI  - Monodisperse Cu/Cu2O@C core-shell nanocomposite supported on rGO layers as an
      efficient catalyst derived from a Cu-based MOF/GO structure.
AB  - A novel copper/copper(i) oxide@carbon (Cu/Cu2O@C) core-shell nanocomposite
      monodispersed on the surface of reduced graphene oxide (defined as Cu/Cu2O@C-rGO)
      was synthesized using a one-step calcination of Cu-based metal organic frameworks
      (MOFs)/graphene oxide (GO) composite structure. The size of the resultant
      Cu/Cu2O@C core-shell nanoparticles (NPs) on the rGO layers were mainly
      distributed in range of about 90-100 nm with good dispersion, which was
      characterized using transmission electron microscopy. X-ray diffraction, Raman
      spectroscopy, Fourier transform infrared spectroscopy, nitrogen adsorption
      desorption isotherms, X-ray photoelectron spectrometry and thermogravimetric
      analyses were also carried out to characterize the structure and composition of
      the Cu/Cu2O@C-rGO. The catalytic performance of the Cu/Cu2O@C-rGO composite was
      evaluated using a reduction reaction from 4-nitrophenol to 4-aminophenol. It was
      demonstrated that the Cu/Cu2O@C-rGO composite exhibited an excellent catalytic
      performance, which can reach a nearly 100% conversion rate in 90 s with 0.1 mg of
      catalyst. This catalyst also showed a good performance for the degradation of
      other organic dyes such as methylene blue, methyl orange and rhodamine B.
      Additionally, the core-shell structure exhibited good stability and reusability
      for the reduction reaction, which was because of its relatively better oxidation
      resistance than that of the bare Cu NPs. This research provided an efficient and
      stable non-noble metal-based catalyst derived from the MOF/GO structure.

PMID- 30204203
TI  - Nonequilibrium phase diagrams for actomyosin networks.
AB  - Living cells dynamically modulate the local morphologies of their actin networks
      to perform biological functions, including force transduction, intracellular
      transport, and cell division. A major challenge is to understand how diverse
      structures of the actin cytoskeleton are assembled from a limited set of
      molecular building blocks. Here we study the spontaneous self-assembly of a
      minimal model of cytoskeletal materials, consisting of semiflexible actin
      filaments, crosslinkers, and molecular motors. Using coarse-grained simulations,
      we demonstrate that by changing concentrations and kinetics of crosslinkers and
      motors, as well as filament lengths, we can generate three distinct structural
      phases of actomyosin assemblies: bundled, polarity-sorted, and contracted. We
      introduce new metrics to distinguish these structural phases and demonstrate
      their functional roles. We find that the binding kinetics of motors and
      crosslinkers can be tuned to optimize contractile force generation, motor
      transport, and mechanical response. By quantitatively characterizing the
      relationships between the modes of cytoskeletal self-assembly, the resulting
      structures, and their functional consequences, our work suggests new principles
      for the design of active materials.

PMID- 30204216
TI  - The changing face of percutaneous closure of the patent ductus arteriosus:
      advances over the last few years.

PMID- 30204217
TI  - The African context of the Cape Town Declaration.

PMID- 30204218
TI  - Bongani Mayosi, a hero remembered.

PMID- 30204219
TI  - Does the use of N-butyl-2 cyanoacrylate in the treatment of lower extremity
      superficial varicose veins cause acute systemic inflammation and allergic
      reactions?
AB  - INTRODUCTION: In this study we used N-butyl-2 cyanoacrylate (NBCA), including
      dimethyl sulfoxide (DMSO), via the endovenous route, for mechanochemical ablation
      in the treatment of superficial venous insufficiency, in an attempt to establish
      whether an early systemic inflammatory response and an allergic reaction occurred
      in the patients. METHODS: A total of 102 patients were treated with endovenous
      medical ablation in two centres between October 2015 and February 2016. This
      study was a two-centre, retrospective, non-randomised investigational study.
      Ablation treatment with endovenous NBCA was used in patients with C3 to C4b grade
      superficial venous insufficiency, according to the CEAP (clinical, aetiology,
      anatomy and pathophysiology) clinical classification, with sapheno-femoral
      junctional insufficiency and a reflux of 0.5 seconds and longer on duplex ultra
      sonography. Pre-operative whole blood count, erythrocyte sedimentation rate
      (ESR), C-reactive protein (CRP) level and blood chemistry were studied in all
      patients on admission to the clinic, and repeated in the second hour post
      intervention. RESULTS: All patients were treated successfully. Pre-operative
      white blood cell count (WBC) was 6.82 +/- 1.67 * 109 cells/ul, and post
      intervention it was 6.57 +/- 1.49 * 109 cells/ul; the difference was not
      statistically significant (p = 0.68). The neutrophil count before the
      intervention was 4.09 +/- 1.33 * 109 cells/ul, while afterwards, it was 4.09 +/-
      1.33 * 109 cells/ul, with no statistically significant difference (p = 0.833).
      Pre-intervention eosinophil count was 0.64 +/- 1.51 * 109 cells/ul, while it was
      0.76 +/- 1.65 * 109 cells/ul after the intervention, and the difference was
      statistically significant. Pre-intervention ESR and CRP values were 18.92 +/-
      9.77 mm/h and 1.71 +/- 1.54 mg/dl, respectively. Postoperative ESR and CRP values
      were 19.78 +/- 15.90 mm/h and 1.73 +/- 1.59 mg/dl, respectively, but the
      differences were not statistically significant. When the parameters were analysed
      by gender, the differences between pre- and postoperative WBC and eosinophil
      count, ESR and CRP in women were not statistically significant. On the other
      hand, although the change in WBC count and CRP value were not statistically
      significant in males, the differences in eosinophil count and ESR were
      statistically significant. CONCLUSIONS: Cyanoacrylate has been used in the
      endovenous medical ablation of varicose veins and superficial venous
      insufficiency over the last few years without the use of thermal energy and
      tumescent anaesthesia, which represents the greatest advantage of this method. In
      addition, since it causes no systemic allergic or acute inflammatory reaction, it
      appears to be safe to use.

PMID- 30204220
TI  - Transcatheter closure of the patent ductus arteriosus at a public sector hospital
      in Soweto, South Africa: a review of patient outcomes over 15 years.
AB  - BACKGROUND: Methods of closing patent ductus arteriosus (PDA) have evolved over
      time. We review this development in our setting. METHODS: This was a
      retrospective analysis of children who had transcatheter PDA closure at Chris
      Hani Baragwanath Hospital between 1993 and 2008. RESULTS: Over 15 years, 1 254
      PDAs were diagnosed, of which 293 required intervention; 139 patients had
      transcatheter closure, the median age was 1.8 years (interquartile range = 1-4.5
      years) and 66% were female (92/139). Mean PDA diameter was 3.2 mm (standard
      deviation = 1.6 mm), with an average 2:1 shunt. Transcatheter closure was
      performed using COOK(r) Flipper coils (n = 93) or AmplatzerTM devices (n = 46).
      Early occlusion rates for coils were 52% (39/75) and late occlusion occurred in
      91% (68/75) of patients. For Amplatzer devices, early occlusion rates were 94%
      (33/35) and late occlusion was 100%. AmplatzerTM devices, available since 2003,
      were overwhelmingly used in the later years. CONCLUSIONS: Transcatheter PDA
      closure was safe and effective in this setting, with outcomes similar to reports
      elsewhere.

PMID- 30204221
TI  - Tribute to Professor Bongani Mawethu Mayosi.

PMID- 30204222
TI  - Multivessel disease in STEMI patients: a perspective from limited-resource
      settings.

PMID- 30204223
TI  - Feasibility of south-south collaboration in Africa: the Uganda-Mozambique
      perspective.

PMID- 30204224
TI  - Cases in a series of carcinoid syndrome and carcinoid heart disease.
AB  - Although carcinoid syndrome is regarded as a rare entity, carcinoid patients with
      evidence of cardiac involvement show a markedly reduced survival time. Patients
      with advanced signs of right-sided heart failure represent a subgroup at
      particularly high risk. Echocardiography remains the gold standard to diagnose or
      confirm structural cardiac involvement in patients with underlying carcinoid
      disease. This is the notion that propelled us to report on cases of carcinoid
      syndrome with cardiac involvement. We also review carcinoid syndrome and
      carcinoid heart disease, and challenges regarding the diagnosis and management of
      carcinoid heart disease.

PMID- 30204225
TI  - [Misleading study in The Lancet on the outcome of the Swedish AAA screening
      program].
AB  - In a recent publication in The Lancet Johansson and colleagues claim no effect on
      aneurysm mortality among men participating in the Swedish AAA screening program,
      and question its justification. The study is, however, limited by a corrupt study
      design and incorrect data, making the publication misleading. On the contrary,
      several RCTs and contemporary nationwide data with sufficient follow-up clearly
      show that AAA screening saves lives and is highly cost-effective. The program has
      so far identified about 6000 men with an AAA, of whom 1500 have been operated on
      to prevent rupture. Thus, more than 750 men have experienced a longer life (by a
      mean of 8 years) as a result of the program. Continuous evaluation of the program
      is important but requires a scientifically sound methodology.

PMID- 30204226
TI  - ?

PMID- 30204227
TI  - [A retrospective analysis of the management of unconscious patients from the
      emergency room (ER) to intensive care (ICU) at Sodersjukhuset].
AB  - Intubation and admission to ICU are vital stages in the management of unconscious
      patients. Treatment records for all patients who died within 5 days of admission
      to Sodersjukhuset during 2015 were obtained. Patients with GCS <9 in the ER were
      selected. It was noted if the patients had been intubated, had done a CT brain
      scan and if they had been admitted to ICU. They were divided into one of three
      diagnosis groups: cardiac arrest, intracerebral hemorrhage/stroke or other. 48 of
      51 cardiac arrest patients were intubated and transferred to ICU. Only 17 of 46
      ICH/stroke patients were intubated, and 22 ICH/stroke patients did a CT brain
      scan with an unprotected airway. Possible organ donors were more difficult to
      detect in the cardiac arrest group (6 of 14 possible) compared with the
      ICH/stroke group (12 of 14 possible). Our analysis shows that improvements need
      to be made in the airway management of unconscious patients who have suffered an
      ICH or stroke, and that identification of possible organ donors amongst victims
      of cardiac arrest also needs to be improved.

PMID- 30204228
TI  - [Electrochemotherapy - a simple and effective treatment of skin metastases].
AB  - Electrochemotherapy is  a simple and effective treatment of skin metastases.
      Electrochemotherapy is possible after previous surgery, radiotherapy and/or limb
      perfusion. Electrochemotherapy is most likely an under-used treatment modality in
      Sweden.

PMID- 30204229
TI  - Induced pluripotent stem cells for cartilage repair: current status and future
      perspectives.
AB  - The establishment of cartilage regenerative medicine is an important clinical
      issue, but the search for cell sources able to restore cartilage integrity proves
      to be challenging. Human mesenchymal stromal cells (MSCs) are prone to form
      epiphyseal or hypertrophic cartilage and have an age-related limited
      proliferation. On the other hand, it is difficult to obtain functional
      chondrocytes from human embryonic stem cells (ESCs). Moreover, the ethical issues
      associated with human ESCs are an additional disadvantage of using such cells.
      Since their discovery in 2006, induced pluripotent stems cells (iPSCs) have
      opened many gateways to regenerative medicine research, especially in cartilage
      tissue engineering therapies. iPSCs have the capacity to overcome limitations
      associated with current cell sources since large numbers of autologous cells can
      be derived from small starting populations. Moreover, problems associated with
      epiphyseal or hypertrophic-cartilage formation can be overcome using iPSCs. iPSCs
      emerge as a promising cell source for treating cartilage defects and have the
      potential to be used in the clinical field. For this purpose, robust protocols to
      induce chondrogenesis, both in vitro an in vivo, are required. This review
      summarises the recent progress in iPSC technology and its applications for
      cartilage repair.

PMID- 30204230
TI  - Acute changes in cardiac function by direct acting antiviral therapy for
      hepatitis C-infected patients with thalassemia.
AB  - BACKGROUND: Patients with thalassemia may also have cardiac abnormalities due to
      congenital problems, anemia, and increased burden of iron in their myocardium.
      This study was designed to evaluate the effects of direct acting antiviral (DAA)
      therapy on the cardiac function of hepatitis C virus (HCV)-infected patients with
      thalassemia. METHOD: HCV-infected thalassemia patients were enrolled to this
      prospective evaluation. Daily tablets of 90 mg Ledipasvir (or 60 mg Daclatasvir)
      plus 400 mg Sofosbuvir (+/-ribavirin) were prescribed for the patients according
      to the Iran Hepatitis Network's guidelines. An echocardiography fellow collected
      the echocardiography findings before and after the treatment of all the patients.
      The patients were followed up for any cardiac events within 12 weeks after
      finishing the treatment. RESULTS: Thirty-two patients with the mean age of 24.2
      +/- 6.4 years were evaluated. All patients showed a sustained virological
      response at the 12th week after finishing the treatment. The patients' left
      ventricular end systolic diameter (3.0 vs 3.24; P = 0.003) and volume (33.8 vs
      43.6; P = 0.001), global longitudinal strain of the left ventricle (-22.0 vs 
      20.6, P = 0.046), and average (-21.4 vs -20.3; P = 0.048), and the right
      ventricle size (3.12 vs 3.31; P = 0.012) were significantly increased after
      finishing the treatment. Changes in the abovementioned parameters were not
      correlated with the patients' myocardium iron load. There were no significant
      differences in other echocardiographic parameters ( P > 0.05) before and after
      the treatment. CONCLUSION: Sofosbuvir-based regimens for HCV treatment were safe
      for our HCV-infected patients with thalassemia. Our patients' ejection fraction
      remained unchanged. Hence, more specialized echocardiographic evaluations were
      recommended for those with a history of cardiac abnormalities, cardiac iron
      overload, and in case of any cardiac adverse event during DAA therapy in patients
      with thalassemia.

PMID- 30204231
TI  - Professor Albert K. Oehling: Allergology reference in the 20th century.

PMID- 30204232
TI  - Timing is everything: maternal circadian rhythms and the developmental origins of
      health and disease.

PMID- 30204233
TI  - Cardiovascular Risk of Nonsteroidal Anti-inflammatory Drugs and Classical and
      Selective Cyclooxygenase-2 Inhibitors: A Meta-analysis of Observational Studies.
AB  - The purpose of this study was to review the published evidence on the clinical
      use of nonsteroidal anti-inflammatory drugs (NSAIDs) and to assess the
      cardiovascular risk (CVR) of cyclooxygenase-2 inhibitors (coxibs), excluding
      aspirin, by means of a meta-analytic procedure. A search was conducted on MEDLINE
      and EMBASE databases between October 1999 and June 2018. Cohort and case-control
      studies showing CVR as relative risk (RR), odds ratio, hazard ratio, or incidence
      rate ratio associated with NSAIDs versus no treatment were selected. We estimated
      the pooled RR and the 95% confidence interval (CI) for all NSAIDs as a whole and
      individually. Eighty-seven studies met the inclusion criteria. Overall, NSAIDs
      were found to be associated with a statistically significantly increased CVR (RR,
      1.24 [95%CI, 1.19-1.28]). The risk was slightly higher for coxibs (RR, 1.22
      [95%CI, 1.17-1.28]) as compared with nonselective NSAIDs (RR, 1.18 [95%CI, 1.12
      1.24]). Data analysis by drug disclosed that rofecoxib (RR, 1.39 [95%CI, 1.31
      1.47]), followed by diclofenac (RR, 1.34 [95%CI, 1.26-1.42]) and etoricoxib (RR,
      1.27 [95%CI, 1.12-1.43]) were the NSAIDs associated with the highest CVR.
      Analysis by type of event showed that the highest risk corresponded to vascular
      events for both coxibs (RR, 2.18 [95%CI, 1.72-2.78]) and nonselective NSAIDs (RR,
      2.46 [95%CI, 2.00-3.02]). The meta-analysis results suggest that the use of the
      marketed coxibs celecoxib and etoricoxib would be related to a statistically
      significant CVR increase. Etoricoxib CVR could be higher than that for celecoxib.
      This increment would be similar to classical NSAID CVR.

PMID- 30204234
TI  - Glutamate Transmission to Ventral Tegmental Area GABA Neurons Is Altered by Acute
      and Chronic Ethanol.
AB  - BACKGROUND: Ventral tegmental area (VTA) GABA neurons have been heavily
      implicated in alcohol reinforcement and reward. In animals that self-administer
      alcohol, VTA GABA neurons exhibit increased excitability that may contribute to
      alcohol's rewarding effects. The present study investigated the effects of acute
      and chronic ethanol exposure on glutamate (GLU) synaptic transmission to VTA GABA
      neurons. METHODS: Whole-cell recordings of evoked, spontaneous, and miniature
      excitatory postsynaptic currents (eEPSCs, sEPSCs, and mEPSCs, respectively) were
      performed on identified GABA neurons in the VTA of GAD67-GFP+ transgenic mice.
      Three ethanol exposure paradigms were used: acute ethanol superfusion; a single
      ethanol injection; and chronic vapor exposure. RESULTS: Acute ethanol superfusion
      increased the frequency of EPSCs but inhibited mEPSC frequency and amplitude.
      During withdrawal from a single injection of ethanol, the frequency of sEPSCs was
      lower than saline controls. There was no difference in alpha-amino-3-hydroxy-5
      methyl-4-isoxazolepropionic acid (AMPA)/N-methyl-d-aspartate (NMDA) ratio between
      neurons following withdrawal from a single exposure to ethanol. However,
      following withdrawal from chronic ethanol, sEPSCs and mEPSCs had a greater
      frequency than air controls. There was no difference in AMPA/NMDA ratio following
      chronic ethanol. CONCLUSIONS: These results suggest that presynaptic mechanisms
      involving local circuit GLU neurons, and not GLU receptors, contribute to
      adaptations in VTA GABA neuron excitability that accrue to ethanol exposure,
      which may contribute to the rewarding properties of alcohol via their regulation
      of mesolimbic dopamine transmission.

PMID- 30204235
TI  - Patient-mediated interventions to improve professional practice.
AB  - BACKGROUND: Healthcare professionals are important contributors to healthcare
      quality and patient safety, but their performance does not always follow
      recommended clinical practice. There are many approaches to influencing practice
      among healthcare professionals. These approaches include audit and feedback,
      reminders, educational materials, educational outreach visits, educational
      meetings or conferences, use of local opinion leaders, financial incentives, and
      organisational interventions. In this review, we evaluated the effectiveness of
      patient-mediated interventions. These interventions are aimed at changing the
      performance of healthcare professionals through interactions with patients, or
      through information provided by or to patients. Examples of patient-mediated
      interventions include 1) patient-reported health information, 2) patient
      information, 3) patient education, 4) patient feedback about clinical practice,
      5) patient decision aids, 6) patients, or patient representatives, being members
      of a committee or board, and 7) patient-led training or education of healthcare
      professionals. OBJECTIVES: To assess the effectiveness of patient-mediated
      interventions on healthcare professionals' performance (adherence to clinical
      practice guidelines or recommendations for clinical practice). SEARCH METHODS: We
      searched MEDLINE, Ovid in March 2018, Cochrane Central Register of Controlled
      Trials (CENTRAL) in March 2017, and ClinicalTrials.gov and the International
      Clinical Trials Registry (ICTRP) in September 2017, and OpenGrey, the Grey
      Literature Report and Google Scholar in October 2017. We also screened the
      reference lists of included studies and conducted cited reference searches for
      all included studies in October 2017. SELECTION CRITERIA: Randomised studies
      comparing patient-mediated interventions to either usual care or other
      interventions to improve professional practice. DATA COLLECTION AND ANALYSIS: Two
      review authors independently assessed studies for inclusion, extracted data and
      assessed risk of bias. We calculated the risk ratio (RR) for dichotomous outcomes
      using Mantel-Haenszel statistics and the random-effects model. For continuous
      outcomes, we calculated the mean difference (MD) using inverse variance
      statistics. Two review authors independently assessed the certainty of the
      evidence (GRADE). MAIN RESULTS: We included 25 studies with a total of 12,268
      patients. The number of healthcare professionals included in the studies ranged
      from 12 to 167 where this was reported. The included studies evaluated four types
      of patient-mediated interventions: 1) patient-reported health information
      interventions (for instance information obtained from patients about patients'
      own health, concerns or needs before a clinical encounter), 2) patient
      information interventions (for instance, where patients are informed about, or
      reminded to attend recommended care), 3) patient education interventions
      (intended to increase patients' knowledge about their condition and options of
      care, for instance), and 4) patient decision aids (where the patient is provided
      with information about treatment options including risks and benefits). For each
      type of patient-mediated intervention a separate meta-analysis was
      produced.Patient-reported health information interventions probably improve
      healthcare professionals' adherence to recommended clinical practice (moderate
      certainty evidence). We found that for every 100 patients consulted or treated,
      26 (95% CI 23 to 30) are in accordance with recommended clinical practice
      compared to 17 per 100 in the comparison group (no intervention or usual care).
      We are uncertain about the effect of patient-reported health information
      interventions on desirable patient health outcomes and patient satisfaction (very
      low-certainty evidence). Undesirable patient health outcomes and adverse events
      were not reported in the included studies and resource use was poorly
      reported.Patient information interventions may improve healthcare professionals'
      adherence to recommended clinical practice (low-certainty evidence). We found
      that for every 100 patients consulted or treated, 32 (95% CI 24 to 42) are in
      accordance with recommended clinical practice compared to 20 per 100 in the
      comparison group (no intervention or usual care). Patient information
      interventions may have little or no effect on desirable patient health outcomes
      and patient satisfaction (low-certainty evidence). We are uncertain about the
      effect of patient information interventions on undesirable patient health
      outcomes because the certainty of the evidence is very low. Adverse events and
      resource use were not reported in the included studies.Patient education
      interventions probably improve healthcare professionals' adherence to recommended
      clinical practice (moderate-certainty evidence). We found that for every 100
      patients consulted or treated, 46 (95% CI 39 to 54) are in accordance with
      recommended clinical practice compared to 35 per 100 in the comparison group (no
      intervention or usual care). Patient education interventions may slightly
      increase the number of patients with desirable health outcomes (low-certainty
      evidence). Undesirable patient health outcomes, patient satisfaction, adverse
      events and resource use were not reported in the included studies.Patient
      decision aid interventions may have little or no effect on healthcare
      professionals' adherence to recommended clinical practice (low-certainty
      evidence). We found that for every 100 patients consulted or treated, 32 (95% CI
      24 to 43) are in accordance with recommended clinical practice compared to 37 per
      100 in the comparison group (usual care). Patient health outcomes, patient
      satisfaction, adverse events and resource use were not reported in the included
      studies. AUTHORS' CONCLUSIONS: We found that two types of patient-mediated
      interventions, patient-reported health information and patient education,
      probably improve professional practice by increasing healthcare professionals'
      adherence to recommended clinical practice (moderate-certainty evidence). We
      consider the effect to be small to moderate. Other patient-mediated
      interventions, such as patient information may also improve professional practice
      (low-certainty evidence). Patient decision aids may make little or no difference
      to the number of healthcare professionals' adhering to recommended clinical
      practice (low-certainty evidence).The impact of these interventions on patient
      health and satisfaction, adverse events and resource use, is more uncertain
      mostly due to very low certainty evidence or lack of evidence.

PMID- 30204236
TI  - Suggestions for Model-Informed Precision Dosing to Optimize Neonatal Drug
      Therapy.
AB  - Evidence for dosing, efficacy, and safety of most medications used to treat
      neonates is sparse. Thus, dosing is usually derived by extrapolation from adult
      and pediatric pharmacologic data with scaling by body weight or body surface
      area. This may lead to drug dosing that is unsafe or ineffective. However, new
      strategies are being developed and studied to dose medications in critically ill
      neonates. Mass spectroscopy technology capable of quickly analyzing drug levels
      is readily available. Software that integrates population pharmacokinetics and
      pharmacodynamics with data from sparse samples from neonates allows for timely
      adjustments of dosing to achieve the desired effect while minimizing adverse
      outcomes. Some genetic polymorphisms that affect drug response in neonates have
      also been reported. This review highlights aspects of drug response and how it is
      impacted by prematurity, assesses pharmacogenomic studies in neonates, and offers
      suggestions for innovative pharmacokinetic/pharmacodynamic model-based approaches
      that combine population- or physiology-based pharmacology data, Bayesian
      analysis, and electronic decision support tools for precision dosing in neonates
      while illustrating examples where this approach can be used to optimize medical
      therapy in neonates. Barriers to implementing precision dosing in neonates and
      how to overcome them are also discussed.

PMID- 30204237
TI  - Cancer Survivorship and Palliative Care: Shared Progress, Challenges, and
      Opportunities.

PMID- 30204238
TI  - Anal incontinence after vaginal delivery or cesarean section.
AB  - INTRODUCTION: Uncertainties remain as to whether a cesarean section is protective
      for the short-term and long-term development of anal incontinence. Our aim was to
      explore whether women who had delivered only vaginally were at greater risk of
      anal incontinence than nulliparous women and women who had undergone cesarean
      sections only. MATERIAL AND METHODS: Background information, medical history, and
      data on anal incontinence (defined as fecal or flatus incontinence weekly or
      more) reported by women participating in a large population-based health survey
      in Norway (the Nord-Trondelag Health Study 3) during the period October 2006 to
      June 2008 were collected and linked to data from the Medical Birth Registry of
      Norway. The prevalence of anal incontinence was calculated and multivariate
      logistic regression analyses were applied. RESULTS: The mean age of the 12 567
      women was 49.9 years. The age and educational level of women who had cesarean
      sections only were similar to those who had a vaginal delivery and obstetric anal
      sphincter injuries (OASIS). Nulliparous women and those who had a vaginal
      delivery and no OASIS were older and had higher educational achievements than
      women who had delivered by cesarean section exclusively, and women with OASIS.
      One in four women with OASIS reported anal incontinence compared with one in six
      of the other women (P < .001). Age, educational level, diarrhea, constipation,
      birthweight, and OASIS increased the risk of anal incontinence in all women.
      Parity was associated with anal incontinence in parous women only. No differences
      were found for fecal urgency. CONCLUSIONS: Women with vaginal deliveries
      complicated by OASIS are at increased risk of anal incontinence. However, no
      increased risk of anal incontinence was found in nulliparous women or women who
      had cesarean sections only or vaginal deliveries not complicated by OASIS.

PMID- 30204239
TI  - Elotuzumab plus lenalidomide and dexamethasone in relapsed/refractory multiple
      myeloma: Extended 4-year follow-up and analysis of relative progression-free
      survival from the randomized ELOQUENT-2 trial.
AB  - BACKGROUND: The randomized phase 3 ELOQUENT-2 study (NCT01239797) evaluated the
      efficacy and safety of elotuzumab plus lenalidomide and dexamethasone (ELd)
      versus lenalidomide and dexamethasone (Ld) in relapsed/refractory multiple
      myeloma (RRMM), and to date, has the longest follow-up of any monoclonal antibody
      in patients with RRMM. METHODS: In this extended 4-year follow-up of the ELOQUENT
      2 trial, the coprimary endpoints of progression-free survival (PFS) and overall
      response rate as well as the secondary endpoint of overall survival were
      assessed. In the absence of head-to-head trials comparing Ld-based triplet
      regimens to guide treatment selection, 4 randomized controlled trials-ELOQUENT-2,
      ASPIRE, TOURMALINE-MM1, and POLLUX-were indirectly compared to provide insight
      into the relative efficacy of these regimens in RRMM. RESULTS: Data at 4 years
      were consistent with 2- and 3-year follow-up data: ELd reduced the risk of
      disease progression/death by 29% versus Ld (hazard ratio, 0.71) while maintaining
      safety. The greatest PFS benefit among the assessed subgroups was observed in
      patients at the median time or further from diagnosis (>=3.5 years) with 1 prior
      line of therapy, who had a 44% reduction in the risk of progression/death, and in
      patients in the high-risk category, who had a 36% reduction in favor of ELd. This
      regimen also showed a relative PFS benefit that was maintained beyond 50 months.
      CONCLUSIONS: The sustained PFS benefit and long-term safety of ELd at 4 years,
      similar to those observed at 2 and 3 years, support ELd as a valuable therapeutic
      option for the long-term treatment of patients with RRMM.

PMID- 30204240
TI  - KSHV viral load and Interleukin-6 in HIV-associated pediatric Kaposi sarcoma
      Exploring the role of lytic activation in driving the unique clinical features
      seen in endemic regions.
AB  - Kaposi sarcoma (KS) is among the most common childhood malignancies in central,
      eastern, and southern Africa. Although its unique clinical features have been
      established, biological mechanisms related to the causative agent, KS-associated
      herpes-virus (KSHV), have yet to be explored in children. We performed a
      prospective observational pilot study to explore associations between KSHV viral
      load (VL), human interleukin-6 (IL-6) and IL-10 levels, and clinical
      characteristics of 25 children with KS in Lilongwe, Malawi from June 2013-August
      2015. The median age was 6.4 years. Lymphadenopathy was the most common site of
      KS involvement (64%), followed by skin and oral mucosa (44% each), woody edema
      (12%), and pulmonary (8%). Baseline samples for plasma KSHV VL, IL-6 and IL-10
      analyses were available for 18/25 patients (72%) at time of KS diagnosis. KSHV VL
      was detectable at baseline in 12/18 (67%) patients, the median baseline IL-6
      level was 8.53 pg/mL (range 4.31-28.33), and the median baseline IL-10 level was
      19.53 pg/mL (range 6.91-419.69). Seven (39%) patients presented with an IL-6
      level > 10 pg/mL (exceeding twice the upper limit of normal). Detectable KSHV VL
      was significantly associated with lymphadenopathic KS (p = 0.004), while having
      undetectable KSHV VL was associated with a higher likelihood of presenting with
      hyperpigmented skin lesions (p = 0.01). Detectable KSHV VL and elevated IL-6
      levels are present in a subset of children with KS. Lytic activation of KSHV and
      associated elevation in KSHV VL may contribute to the unique clinical
      manifestations of pediatric KS in KSHV-endemic regions of Africa.

PMID- 30204241
TI  - Does Family History of Alcohol Use Disorder Relate to Differences in Regional
      Brain Volumes? A Descriptive Review with New Data.
AB  - BACKGROUND: Differences in regional brain volumes as a function of family history
      (FH) of alcohol use disorder (AUD) have been reported, and it has been suggested
      that these differences might index genetic risk for AUD. However, results have
      been inconsistent. The aims of the current study were (i) to provide an updated
      descriptive review of the existing literature and (ii) to examine the association
      of FH with indices of subcortical volumes and cortical thickness in a sample of
      youth recruited based on FH status. METHODS: To address aim 1, a literature
      search located 15 published studies comprising 1,735 participants. Studies were
      characterized according to population, analytic methods, regions of interest, and
      primary findings. To address the second aim, we examined volumetric and cortical
      thickness in a sample of 69 youth (mean age = 19.71 years, SD = 0.79) recruited
      based on FH status and matched on drinking variables. Associations of sex and
      alcohol use with volumetric outcomes were also examined. RESULTS: Our descriptive
      review revealed an inconsistent pattern of results with respect to the presence,
      direction, and regional specificity of volumetric differences across FH groups.
      The most consistent finding, significantly smaller amygdala volumes in FH+
      participants, was not replicated in all studies. In the current sample of youth,
      measures of subcortical volumes and cortical thickness did not significantly
      differ as a function of FH, sex, or their interaction. CONCLUSIONS: Evidence for
      FH group differences in regional brain volumes is inconsistent, and the current
      study failed to detect any group differences. Further research is needed to
      confirm the reproducibility of FH group differences and implications for AUD
      risk.

PMID- 30204242
TI  - Functional and structural profiles of GST gene family from three Populus species
      reveal the sequence-function decoupling of orthologous genes.
AB  - A common assumption in comparative genomics is that orthologous genes are
      functionally more similar than paralogous genes. However, the validity of this
      assumption needs to be assessed using robust experimental data. We conducted
      tissue-specific gene expression and protein function analyses of orthologous
      groups within the glutathione S-transferase (GST) gene family in three closely
      related Populus species: Populus trichocarpa, Populus euphratica and Populus
      yatungensis. This study identified 21 GST orthologous groups in the three Populus
      species. Although the sequences of the GST orthologous groups were highly
      conserved, the divergence in enzymatic functions was prevalent. Through site
      directed mutagenesis of orthologous proteins, this study revealed that
      nonsynonymous substitutions at key amino acid sites played an important role in
      the divergence of enzymatic functions. In particular, a single amino acid
      mutation (Arg39->Trp39) contributed to P. euphratica PeGSTU30 possessing high
      enzymatic activity via increasing the hydrophobicity of the active cavity. This
      study provided experimental evidence showing that orthologues belonging to the
      gene family have functional divergences. The nonsynonymous substitutions at a few
      amino acid sites resulted in functional divergence of the orthologous genes. Our
      findings provide new insights into the evolution of orthologous genes in closely
      related species.

PMID- 30204243
TI  - Ligand-activated interaction of PPARdelta with c-Myc governs the tumorigenicity
      of breast cancer.
AB  - Peroxisome proliferator-activated receptor (PPAR) delta is a promising
      therapeutic target in metabolic and inflammatory disorders. However, its role in
      oncogenesis is controversial, and its therapeutic potential remains to be
      determined. In our study, we show that ligand-activated PPARdelta forms a complex
      with the proto-oncogene product c-Myc. The interaction of PPARdelta with c-Myc
      affected the transcriptional activity of c-Myc and the expression of its target
      genes. The PPARdelta-dependent regulation of c-Myc activity was associated with
      decreased tumorigenicity in breast cancer cells. Administration of the PPARdelta
      ligand GW501516 inhibited tumor growth in xenograft model mice bearing MDA-MB-231
      cells stably expressing wild-type PPARdelta, but not those expressing dominant
      negative PPARdelta, by interfering with c-Myc function through protein-protein
      interaction. Our results indicating that PPARdelta forms an antitumorigenic
      complex with c-Myc in the presence of ligand suggest a potential role of
      PPARdelta in breast cancer development.

PMID- 30204244
TI  - Ability of inactivated vaccines based on far-eastern tick-borne encephalitis
      virus strains to induce humoral immune response in originally seropositive and
      seronegative recipients.
AB  - Tick-borne encephalitis (TBE) remains one of the major public health concerns in
      northern Eurasia, and its' area is expanding. TBE virus (TBEV) includes three
      subtypes and several monophyletic groups, cocirculating in Russia. Five
      inactivated vaccines are used for TBE prophylaxis. The rising number of people
      subjected to vaccination brings up the issue of the impact of individual
      recipient characteristics on vaccination efficacy. The present work studies
      correlations among the vaccination scheme, sex, age, body mass index (BMI),
      chronic diseases, postvaccinal reaction, pre-existing anti-TBEV antibodies, and
      postvaccinal humoral immunity development. Sera were collected during clinical
      trials in the TBEV Siberian subtype endemic area. Adult recipients were
      vaccinated with Tick-E-Vac and EnceVir vaccines based on Far-Eastern TBEV
      strains. Vaccine ability to induce humoral immunity in different categories of
      recipients was estimated by seroconversion rates and the percentage of recipients
      with high neutralizing antibody titers (>=1:500). High immunogenicity of vaccines
      based on Far-Eastern TBEV strains in the TBEV Siberian subtype endemic area in
      all groups of recipients was demonstrated. Impact of pre-existing contact with
      the virus and high BMI on humoral immune response development 14 days after the
      first immunization was evidenced. Nevertheless, the difference was significantly
      less pronounced 30 days after the first vaccination and undetectable after the
      second one.

PMID- 30204245
TI  - Lifestyle factors and health-related quality of life in adult survivors of
      childhood cancer: A report from the St. Jude Lifetime Cohort Study.
AB  - BACKGROUND: Survivors of childhood cancer report poor health-related quality of
      life (HRQOL). Modifiable lifestyle factors such as nutrition and physical
      activity represent opportunities for interventions to improve HRQOL. METHODS: The
      authors examined the association between modifiable lifestyle factors and HRQOL
      among 2480 adult survivors of childhood cancer in the St. Jude Lifetime Cohort
      Study. Dietary intake, physical activity, cigarette smoking, and alcohol
      consumption were assessed through questionnaires. Weight and height were measured
      in the clinic. HRQOL was evaluated using the Medical Outcome Study 36-Item Short
      Form Survey. The physical component summary (PCS), mental component summary
      (MCS), and 8 domain scores of HRQOL were calculated. Multivariable linear
      regression models were used to estimate regression coefficients (beta) associated
      with HRQOL differences. RESULTS: Being physically active (PCS beta = 3.10; and
      MCS beta = 1.48) was associated with higher HRQOL whereas current cigarette
      smoking (PCS beta = -2.30; and MCS beta = -6.49) and obesity (body mass index
      >=30 kg/m2 ) (PCS beta = -3.29; and MCS beta = -1.61) were associated with lower
      HRQOL in both the physical and mental domains. Better diet (Healthy Eating Index
      2015) was associated with higher physical HRQOL (PCS beta = 1.79). Moderate
      alcohol consumption was associated with higher physical (PCS beta = 1.14) but
      lower mental (MCS beta = -1.13) HRQOL (all P <.05). Adherence to multiple healthy
      lifestyle factors demonstrated a linear trend with high scores in both physical
      and mental HRQOL (highest vs lowest adherence: PCS beta = 7.60; and MCS beta =
      5.76 [P for trend, <.0001]). CONCLUSIONS: The association between healthy
      lifestyle factors and HRQOL is cumulative, underscoring the importance of
      promoting multiple healthy lifestyles to enhance HRQOL in long-term survivors of
      childhood cancer.

PMID- 30204246
TI  - Alternative food matrices for snack formulations in terms of acrylamide formation
      and mitigation.
AB  - BACKGROUND: The salty snack market is re-inventing itself trying to offer to
      consumers healthier and added-value products often based on alternative
      vegetables/cereals, such as vegetable chips. New options mostly involve a
      nutritional improvement but the toxicological aspects of the reformulation are
      not usually examined. This work evaluated the acrylamide formation and
      effectiveness of different mitigation strategies in potato chips and in
      alternative snacks, such as carrot and pumpkin chips. Fresh potato, carrot and
      pumpkin samples were fried under controlled conditions and after being subjected
      to different operations (soaking in water at different times/temperatures, adding
      lemon or vinegar as pH modifiers or salt). RESULTS: Acrylamide values in control
      samples of carrot (224 +/- 47 ug kg-1 ) and pumpkin (514 +/- 83 ug kg-1 ) were
      significantly lower than in the potato chip samples (3887 +/- 509 ug kg-1 ). The
      different mitigation treatments had effects on potato and pumpkin chips, the most
      effective strategies being soaking options and the decrease of the pH of the
      medium. However, such treatments were not as effective in carrot chips.
      CONCLUSIONS: These new vegetable snacks could be a healthy alternative both at
      nutritional and toxicological level. In addition, acrylamide concentration could
      even be reduced with simple mitigation operations before frying. (c) 2018 Society
      of Chemical Industry.

PMID- 30204247
TI  - The use of neoadjuvant larotrectinib in the management of children with locally
      advanced TRK fusion sarcomas.
AB  - BACKGROUND: The highly selective oral tropomyosin receptor kinase (TRK) inhibitor
      larotrectinib has demonstrated significant activity in adult and pediatric TRK
      fusion cancers. In the current study, the authors describe the clinical course of
      children with locally advanced TRK fusion sarcoma who were treated preoperatively
      with larotrectinib and underwent subsequent surgical resection. METHODS: A total
      of 24 children were treated on a pediatric phase 1 trial of larotrectinib
      (ClinicalTrials.gov identifier NCT02637687). Five children who had a documented
      TRK fusion sarcoma and underwent surgical resection were included in the current
      analysis. Tumor response (Response Evaluation Criteria In Solid Tumors [RECIST]
      version 1.1) and surgical outcomes were collected prospectively. RESULTS: A total
      of 5 patients (median age, 2 years; range, 0.4-12 years) had locally advanced
      infantile fibrosarcoma (3 patients) or soft-tissue sarcoma (2 patients). Four
      patients had disease that was refractory to standard therapy. All 5 patients
      achieved a partial response to larotrectinib by version 1.1 of RECIST and
      underwent surgical resection after a median of 6 cycles (range, 4-9 cycles) of
      treatment. Surgical resections were R0 (negative resection margins with no tumor
      at the inked resection margin) in 3 patients, R1 (microscopic residual tumor at
      the resection margin) in 1 patient, and R2 (macroscopic residual tumor at the
      resection margin) in 1 patient. Three patients achieved complete (2 patients) or
      near-complete (>98% treatment effect; 1 patient) pathologic responses. These
      patients remained in follow-up and were no longer receiving larotrectinib for a
      minimum of 7 to 15 months postoperatively. Two patients had viable tumor at the
      time of surgical resection and positive resection margins and continued to
      receive adjuvant larotrectinib. No patients experienced postoperative
      complications or wound healing issues. CONCLUSIONS: Children with locally
      advanced TRK fusion sarcomas may proceed to surgical resection after treatment
      with the selective TRK inhibitor larotrectinib, thereby sparing them the
      potentially significant morbidity noted with current approaches. These results
      support the evaluation of larotrectinib as presurgical therapy in children with
      newly diagnosed TRK fusion sarcomas.

PMID- 30204249
TI  - The Efficacy of Preschool Developmental Indicators as a Screen for Early Primary
      School-Based Literacy Interventions.
AB  - Literacy success lays the foundation for children's later educational, health,
      and well-being outcomes. Thus, early identification of literacy need is vital.
      Using data from New Zealand's national preschool health screening program for
      fiscal years 2010/2011-2014/2015, demographic and health variables from 255,090
      children aged 4 years were related to whether they received a literacy
      intervention in early primary school. Overall, 20,652 (8.1%) children received an
      intervention. Time-to-event analysis revealed that all considered variables were
      significantly related to literacy intervention (all p < .01), but the full model
      lacked reasonable predictive power for population screening purposes (Harrell's c
      statistic = .624; 95% CI [.618, .629]). Including more direct literacy measures
      in the national screening program is likely needed for improvement.

PMID- 30204250
TI  - President's message: What a program of nursing research should be.

PMID- 30204248
TI  - Reduction in Nonabstinent WHO Drinking Risk Levels and Change in Risk for Liver
      Disease and Positive AUDIT-C Scores: Prospective 3-Year Follow-Up Results in the
      U.S. General Population.
AB  - BACKGROUND: Abstinence is often the treatment aim for alcohol use disorders
      (AUD), but this may deter individuals who prefer drinking reduction goals from
      entering treatment, and be an overly restrictive end point in alcohol clinical
      trials. Nonabstinent drinking reductions that predict improvement in how
      individuals feel or function may be useful clinical trial outcomes, for example,
      reductions in the 4-category World Health Organization (WHO) drinking risk
      levels. To investigate the clinical relevance of these reductions, we examined
      their relationship with 2 outcomes of interest to medical providers: liver
      disease, and positive scores on an alcohol screening measure. METHODS: Current
      drinkers in a U.S. national survey (n = 21,925) were interviewed in 2001 to 2002
      (Wave 1) and re-interviewed 3 years later (Wave 2). WHO drinking risk levels,
      liver disease, and the Alcohol Use Disorders Identification Test-Consumption
      (AUDIT-C) were assessed at both waves. Adjusted odds ratios (aORs) were used to
      indicate the association of change in WHO drinking risk levels with Wave 2 liver
      disease and AUDIT-C scores. RESULTS: Wave 1 very-high-risk drinkers who reduced
      1, 2, or 3 WHO drinking risk levels had significantly lower odds of Wave 2 liver
      disease (aORs = 0.34, 0.23, 0.17) and positive AUDIT-C scores (aORs = 0.27, 0.09,
      0.03). Wave 1 high-risk drinkers who reduced 1 or 2 WHO risk levels had
      significantly lower odds of positive AUDIT-C scores (aORs = 0.61, 0.25).
      Adjusting for alcohol dependence or AUDIT-C scoring variations did not affect
      results. CONCLUSIONS: In the highest-risk drinkers, reductions in WHO drinking
      risk levels predicted lower likelihood of liver disease and positive AUDIT-C
      scores. Results add to findings that reductions in the 4-category WHO drinking
      risk levels are a meaningful indicator of how individuals feel and function, and
      could serve as nonabstinent end points in clinical trials. Results also connect
      the WHO risk drinking levels to commonly used alcohol screening questions, which
      may be more familiar to healthcare providers.

PMID- 30204251
TI  - GNAS, GNAQ, and GNA11 alterations in patients with diverse cancers.
AB  - BACKGROUND: Advances in deep sequencing technology have uncovered a widespread,
      protumorigenic role of guanine nucleotide-binding (G protein) alpha (GNA)
      subunits, particularly GNA subunits Gs (GNAS), Gq (GNAQ), and G11 (GNA11) (GNA*),
      in a diverse collection of malignancies. The objectives of the current study
      were: 1) to determine GNA* aberration status in a cohort of 1348 patients with
      cancer and 2) to examine tumor mutational burden, overall survival rates, and
      treatment outcomes in patients with GNA*-positive tumors versus those with tumors
      that had wild-type GNA*. METHODS: For each patient, clinical and genomic data
      were collected from medical records. Next-generation sequencing was performed for
      each patient (range, 182-236 genes). RESULTS: Aberrations of GNA* genes were
      identified in a subset of patients who had 8 of the 12 cancer types examined, and
      a significant association was observed for appendiceal cancer and ocular melanoma
      (P < .0001 for both; multivariate analysis). Overall, 4.1% of the cancer
      population was affected. GNA* abnormalities were associated with higher numbers
      of co-alterations in univariate (but not multivariate) analysis and were most
      commonly accompanied by Aurora kinase A (AURKA), Cbl proto-oncogene (CBL), and
      LYN proto-oncogene (LYN) co-alterations (all P < .0001; multivariate analysis).
      GNA* alterations were correlated with a trend toward lower median overall
      survival (P = .085). The median tumor mutational burden was 4 mutations per
      megabase in both GNA*-altered and GNA* wild-type tumors. For this limited sample
      of GNA*-positive patients, longer survival was not correlated with any specific
      treatment regimens. CONCLUSIONS: In the current sample, the genes GNAS, GNAQ, and
      GNA11 were widely altered across cancer types, and these alterations often were
      accompanied by specific genomic abnormalities in AURKA, CBL, and LYN. Therefore,
      targeting GNA* alterations may require drugs that address the GNA* signal and
      important co-alterations. Cancer 2018;00:000-000. (c) 2018 American Cancer
      Society.

PMID- 30204252
TI  - Patient-Focused Drug Development Methods for Benefit-Risk Assessments: A Case
      Study Using a Discrete Choice Experiment for Antiepileptic Drugs.
AB  - Regulatory decisions may be enhanced by incorporating patient preferences for
      drug benefit and harms. This study demonstrates a method of weighting clinical
      evidence by patients' benefit-risk preferences. Preference weights, derived from
      discrete choice experiments, were applied to clinical trial data to estimate the
      expected utility of alternative drugs. In a case study, the rank ordering of
      antiepileptic drugs (AEDs), as indicated from clinical studies, was compared with
      ordering based on weighting clinical evidence by patients' preferences. A
      statistically significant change in rank ordering of AEDs was observed for women
      of childbearing potential who were prescribed monotherapy for generalized or
      unclassified epilepsy. Rank ordering inferred from trial data, valproate >
      topiramate > lamotrigine, was reversed. Modeling the expected utility of drugs
      might address the need to use more systematic, methodologically sound approaches
      to collect patient input that can further inform regulatory decision making.

PMID- 30204255
TI  - Courses and Conferences.

PMID- 30204254
TI  - A cross-sectional serum investigation of a clustering hepatitis C virus infection
      in Southwest China.
AB  - Serum samples were collected in a village with a clustering hepatitis C virus
      (HCV) infection. HCV antibody, HCV RNA loads, liver function indexes, HCV
      envelope antibody, and neutralizing activity were assessed. Among 851 adult sera,
      342 samples were positive for anti-HCV. Of these positive samples, 254 (74.3%)
      were HCV RNA positive (>=800 copies/mL). None of the 69 children's sera were
      positive for HCV antibody or RNA. Among the HCV antibody positive sera, alanine
      aminotransferase, and aspartate aminotransferase levels increased with the higher
      virus loads, but decreased when virus loads were higher than 1 * 10 6  copies/mL.
      HCV envelope antibody and neutralizing antibody levels increased with viral load.

PMID- 30204253
TI  - A simultaneous oral and intramuscular prime/sublingual boost with a DNA/Modified
      Vaccinia Ankara viral vector-based vaccine induces simian immunodeficiency virus
      specific systemic and mucosal immune responses in juvenile rhesus macaques.
AB  - BACKGROUND: A pediatric vaccine to prevent breast milk transmission of human
      immunodeficiency virus (HIV) may generate greater immune responses at viral entry
      sites if given by an oral route. METHODS: We compared immune responses induced in
      juvenile macaques by prime/boosting with simian immunodeficiency virus (SIV)
      expressing DNA/modified vaccinia Ankara virus (MVA) by the intramuscular route
      (IM), the oral (O)/tonsillar routes (T), the O/sublingual (SL) routes, and
      O+IM/SL routes. RESULTS: O/T or O/SL immunization generated SIV-specific T cells
      in mucosal tissues but failed to induce SIV-specific IgA in saliva or stool or
      IgG in plasma. IM/IM or O+IM/SL generated humoral and cellular responses to SIV.
      IM/IM generated greater frequencies of TFH in spleen, but O+IM/SL animals had
      higher avidity plasma IgG and more often demonstrated mucosal IgA responses.
      CONCLUSION: These results suggest that codelivery of HIV DNA/MVA vaccines by the
      oral and IM routes might be optimal for generating both systemic and mucosal
      antibodies.

PMID- 30204256
TI  - Future directions in animal models of Alzheimer's disease.

PMID- 30204258
TI  - Pseudovascular squamous cell carcinoma: A review of the published work and
      reassessment of prognosis.
AB  - A 90-year-old Japanese woman presented with a dome-shaped, dark-red, ulcerated
      nodule measuring 23 mm * 19 mm * 9 mm on the right side of the nasal root.
      Histologically, anastomosing cord-like arrays of atypical polygonal keratinocytes
      exhibiting internal pseudolumina containing detached cells and erythrocytes were
      observed. Although acantholytic and cohesive areas overlapped, cancer pearls were
      not detected. The lower epidermis partially demonstrated scattered dyskeratotic
      and acantholytic keratinocytes with loss of polarity, continuous with an
      underlying tumor mass. The tumor cells were positive for a variety of
      cytokeratins, p40 and vimentin. The Ki-67 proliferation index was 50-60%. Both
      CD31 and CD34 were expressed in reactive blood vessels of the tumor. A local
      excision margined by 1 mm was performed, followed by X rays and electron beam
      irradiation. Neither lymph node nor distant metastasis has appeared over the 14
      months since the excision. We performed a review of the published work and
      identified 24 previously reported patients with pseudovascular squamous cell
      carcinoma of the skin, oral mucosa and vulva to reassess the prognosis of this
      tumor. In 12 of these patients (50%), sites other than the head and neck were
      involved. Eight (33%) tumor-associated deaths occurred. It is believed that
      pseudovascular squamous cell carcinoma has a tendency to develop at morbid skin
      and mucous membranes sites in organs other than the face and neck and to possess
      an aggressive clinical behavior.

PMID- 30204257
TI  - Profile fluctuation of peripheral blood in advanced melanoma patients treated
      with nivolumab.
AB  - Melanoma is a malignant tumor of the melanocytes with an unfavorable clinical
      behavior. Nivolumab, a representative anti-programmed death 1 (PD-1) antibody,
      has recently been used for the treatment of metastatic malignant melanoma.
      However, there have been few appropriate biomarkers predicting the effect of
      nivolumab before the administration. Furthermore, the detailed characteristics of
      peripheral blood mononuclear cell (PBMC) profiles during nivolumab treatment
      remains unclear. In this study, we investigated fluctuations of PBMC profile
      during nivolumab treatment. PBMC analysis showed T-helper (Th)2-dominant
      conditions after a first course of nivolumab treatment. In a favorable case
      treated with nivolumab, a Th1/T-cytotoxic 1 shift was observed after nivolumab
      was administrated. These results suggest that flow cytometric analysis of PBMC
      may be helpful for the treatment of nivolumab.

PMID- 30204259
TI  - Therapeutic synergy between contact dermatitis from a wig-fixing device and
      tofacitinib on alopecia areata.

PMID- 30204260
TI  - Signaling pathways and therapeutic perspectives related to environmental factors
      associated with multiple sclerosis.
AB  - Multiple sclerosis (MS) is an immune-mediated demyelinating disorder of unknown
      etiology. Both genetic-susceptibility and environment exposures, including
      vitamin D deficiency, Epstein-Barr viral and Herpesvirus (HHV-6) infections are
      strongly implicated in the activation of T cells and MS-pathogenesis. Despite
      precise knowledge of how these factors could be operating alone or in combination
      to facilitate and aggravate the disease progression, it is clear that prolonged
      induction of inflammatory molecules and recruitment of other immune cells by the
      activated T cells results in demyelination and axonal damage. It is imperative to
      understand the risk factors associated with MS progression and how these factors
      contribute to disease pathology. Understanding of the underlying mechanisms of
      what factors triggers activation of T cells to attack myelin antigen are
      important to strategize therapeutics and therapies against MS. Current review
      provides a detailed literature to understand the role of both pathogenic and non
      pathogenic factors on the impact of MS.

PMID- 30204261
TI  - Rheological properties of sickle erythrocytes in patients with sickle-cell
      anemia: The effect of hydroxyurea, fetal hemoglobin, and alpha-thalassemia.
AB  - OBJECTIVE: Determine the effect of fetal hemoglobin (HbF) and alpha-thalassemia
      on red blood cell (RBC) deformability of patients with sickle-cell anemia (SCA)
      with and without hydroxyurea (HU). METHODS: Adult patients were enrolled in the
      Sickle Cell Program of the Cardeza Foundation (Thomas Jefferson University) and
      were followed up prospectively during the period in which the Multicenter Study
      of Hydroxyurea (MSH) in patients with SCA was conducted. Ninety-one patients did
      not receive HU, 20 patients were enrolled in MSH, and 10 patients were enrolled
      in an open-label study of HU in SCA. Of the 20 patients enrolled in MSH, 11 took
      HU and nine took placebo. Control group included 113 normal individuals. Red
      blood cell deformability index (DI) was measured by ektacytometry. RESULTS:
      Patients with SCA taking HU (n = 21) had higher DI than those taking placebo (n =
      9) or who were not taking this therapy (n = 91). In patients without therapy,
      those with alpha-thalassemia (n = 31) had higher DI than those without. We showed
      a significant positive correlation between the level of HbF and DI. SCA patients
      without alpha-thalassemia and HbF <10% (n = 48) had lower DI than patients with
      alpha-thalassemia and HbF <10% (n = 23) and patients with (n = 8) or without
      alpha-thalassemia but with HbF >10% (n = 12). DI measured in patients without
      alpha-thalassemia and HbF >10% was higher than in the three other subgroups.
      CONCLUSION: Elevated levels of HbF with or without HU and alpha-thalassemia
      improve sickle RBC rheology, which, in turn, improve the clinical picture of SCA.

PMID- 30204262
TI  - Natives as international medical graduates: A nationwide analysis in Taiwan.
AB  - INTRODUCTION: International medical graduates (IMGs) play an important role in
      many Western countries because of globalization and physician shortages. While
      the IMGs investigated in most studies were immigrants, few studies have
      considered the situation in which people native to a given country have studied
      medicine abroad and then returned to practice in their home country. To
      illustrate that situation, our study aimed to investigate practicing IMGs in
      Taiwan by comparing practicing physicians' nationalities to the countries in
      which the medical schools the IMGs graduated from are located. METHODS: Data were
      obtained from the annual official statistics released by the Taiwan Medical
      Association from 1998 to 2017. RESULTS: The number of practicing IMGs in Taiwan
      increased from 834 (3.1% of 26,991 physicians) in 1998 to 1,733 (3.7% of 46,452)
      in 2017. Their medical schools were distributed across 37 countries, with
      graduates of schools in the Philippines (n = 550), Poland (n = 420), and Myanmar
      (n = 364) accounting for 77.0% of all practicing IMGs in 2017. However, only 29,
      0, and 253 physicians were themselves Filipinos, Polish, and Myanmarese,
      respectively. CONCLUSION: Most of the practicing IMGs in Taiwan are native
      Taiwanese. The real impact of IMGs in health policy-making and the existing quota
      system of admissions to medical schools thus deserve further investigations.

PMID- 30204263
TI  - Prevalence of abnormal semen analysis and levels of adherence with fertility
      preservation in men undergoing therapy for newly diagnosed cancer: A
      retrospective study in 2906 patients.
AB  - BACKGROUND: Sperm cryopreservation (freezing) should be offered to all men with
      cancer due to risk of infertility. However, many men with cancer already have
      impaired spermatogenesis prior to sperm cryopreservation. Furthermore, physical
      ill-health may hinder attendance of freeze visits. Investigating both the
      distribution of sperm functions and freeze attendance rates in men with newly
      diagnosed cancer, may identify patients benefiting from targeted reproductive
      fertility support. METHODS: We performed a retrospective study of 2906 male
      patients undergoing sperm cryopreservation prior to cancer therapy at a single UK
      tertiary centre between 1989 and 2013; all patients were asked to attend three
      hospital semen collection visits prior to cancer therapy. RESULTS: Fifteen per
      cent (433/2906) of men with newly diagnosed cancer had severely impaired semen
      quality (i.e., sperm total motile count, TMC < 1 million) during the first semen
      collection visit. However, patients with severely impaired semen quality had the
      poorest attendance of subsequent semen collection visits despite being requested
      to do so (non-attendance in TMC < 1 million: 43.4%; TMC < 1-30 million: 35.7%, P
      < 0.05 vs. <1 million; TMC > 30 million: 33.2%, P < 0.01 vs. <1 million).
      CONCLUSIONS: This study expands understanding of the semen quality of men with
      newly diagnosed cancer, and their ability to adhere to fertility preservation
      recommendations. Our data suggest that patients with the poorest semen quality
      paradoxically suffer the poorest attendance rates of sperm cryopreservation
      appointments prior to commencing cancer therapy. We suggest that additional
      support may be of clinical benefit to men with newly diagnosed cancer and TMC < 1
      million sperm.

PMID- 30204264
TI  - Epidermal mast cells in Bowenoid papulosis during topical imiquimod therapy.

PMID- 30204265
TI  - Remission of psoriasis with nintedanib for the treatment of idiopathic pulmonary
      fibrosis.

PMID- 30204266
TI  - Use of immune checkpoint inhibitors prolonged overall survival in a Japanese
      population of advanced malignant melanoma patients: Retrospective single
      institutional study.
AB  - Although recent clinical trials have revealed that immune checkpoint inhibitors
      significantly improved the overall survival (OS) of patients with advanced
      melanoma, these previous studies comprised mainly white populations, in which
      superficial spreading melanoma (SSM) and lentigo maligna melanoma are the major
      clinical types of melanoma. In contrast, Asians manifest a distinct
      clinicopathological type of melanoma from that of whites and show much higher
      frequencies of acral lentiginous melanoma (ALM) and mucosal melanoma, which have
      been shown to be less susceptible to immune checkpoint inhibitors. Because no
      comparative studies have been published showing improvement of OS by immune
      checkpoint inhibitors in Asian melanoma patients, we retrospectively collected
      the data for 45 melanoma patients treated with checkpoint inhibitors and 24
      melanoma patients treated with chemotherapy alone before immune checkpoint
      inhibitors became available, and compared their OS. The results showed that the
      patients treated with immune checkpoint inhibitors had significantly better OS
      than did those treated with chemotherapy alone (P < 0.0001). Improved OS was
      observed in both the SSM and the ALM patients. In addition, multivariate Cox
      regression analyses revealed that use of immune checkpoint inhibitors was
      associated with favorable prognosis (P = 0.0001), indicating that use of immune
      checkpoint inhibitors is an independent factor for favorable survival. Our study
      showed that immune checkpoint inhibitors may also improve the prognosis of Asian
      melanoma patients.

PMID- 30204267
TI  - Serum KL-6 levels in Japanese patients with psoriasis treated with secukinumab.

PMID- 30204268
TI  - Arthroderma chiloniense sp. nov. isolated from human stratum corneum: Description
      of a new Arthroderma species.
AB  - A 68-year-old woman was submitted to our hospital because of erythematous and
      scaly skin lesions. To exclude tinea samples of stratum corneum were collected
      and used for mycological investigations. In this material, no fungal elements
      were detected microscopically, but inoculation on Sabouraud agar with
      cycloheximide yielded a presumptive dermatophyte fungus. Subsequent detailed
      investigations with conventional morphological and physiological methods and a
      phylogenetic analysis of the combined LSU rRNA gene (D1/D2 domains) and ITS
      region sequences suggested that the fungus represents a hitherto undescribed
      species of the genus Arthroderma. Here, we describe this species as Arthroderma
      chiloniense sp. nov., EMBL accession no. LT992885. This new species can be
      distinguished from phylogenetically related Arthroderma species using ribosomal
      ITS and LSU genes, and 60S L10 protein sequences; specific macroscopic,
      microscopic and physiological features are lacking. Our attempts to re-isolate
      this fungus from the patient's skin failed although her skin lesions persisted.
      Most likely A. chiloniense is a geophilic species that incidentally contaminated
      or transiently colonised the patient's skin. To avoid diagnostic
      misinterpretations, it is necessary to distinguish A. chiloniense from truly
      pathogenic dermatophytes like Trichophyton (T.) rubrum and T. interdigitale which
      can easily be confused with A. chiloniense based on similar mycelium morphology.

PMID- 30204269
TI  - Reactivation of Chagas disease among heart transplant recipients in the United
      States, 2012-2016.
AB  - BACKGROUND: Heart transplantation has been shown to be a safe and effective
      intervention for progressive cardiomyopathy from chronic Chagas disease. However,
      in the presence of the immunosuppression required for heart transplantation, the
      likelihood of Chagas disease reactivation is significant. Reactivation may cause
      myocarditis resulting in allograft dysfunction and the rapid onset of congestive
      heart failure. Reactivation rates have been well documented in Latin America;
      however, there is a paucity of data regarding the risk in non-endemic countries.
      METHODS: We present our experience with 31 patients with chronic Chagas disease
      who underwent orthotopic heart transplantation in the United States from 2012 to
      2016. Patients were monitored following a standard schedule. RESULTS: Of the 31
      patients, 19 (61%) developed evidence of reactivation. Among the 19 patients, a
      majority (95%) were identified by laboratory monitoring using polymerase chain
      reaction testing. One patient was identified after the onset of clinical symptoms
      of reactivation. All subjects with evidence of reactivation were alive at follow
      up (median: 60 weeks). CONCLUSIONS: Transplant programs in the United States are
      encouraged to implement a monitoring program for heart transplant recipients with
      Chagas disease. Our experience using a preemptive approach of monitoring for
      Chagas disease reactivation was effective at identifying reactivation before
      symptoms developed.

PMID- 30204270
TI  - What information is communicated by radiation therapists to patients during
      education sessions on the first day of treatment?
AB  - This study examined the content covered by radiation therapists (RTs) during
      education sessions; the frequency and types of questions asked by patients; and
      the relationship between patient characteristics and the number of questions
      asked. Fifty-eight education sessions were audio-recorded and transcribed
      verbatim. A coding scheme was developed to examine the frequency of topics
      covered. It comprised 16 topics under four themes: (a) treatment schedule, (b)
      procedural information, (c) treatment-related side effects and (d) who will be
      involved in treatment provision. All education sessions covered information about
      the treatment plan (n = 58, 100%), and the majority described procedural
      information about what happens in the treatment room (n = 56, 97%). Least
      information was given about who will be providing treatment. On average, patients
      asked a mean of 6 questions (SD = 4.95; range = 0-28). Most frequently asked
      questions concerned the general treatment (logistics, schedule), accounting for
      67% of all questions asked. The least common types of questions were related to
      the impact of treatment (6%). There were no statistically significant differences
      in the total number of questions and patient demographics. Patients are provided
      with most, but not all, of the recommended information. Tailoring of information
      by RTs was enabled in response to questions asked.

PMID- 30204271
TI  - Relevance of low specific IgE levels to egg, milk and peanut in infancy.
AB  - BACKGROUND: IgE sensitization is usually associated with allergy-related
      diseases, but may also occur in asymptomatic individuals. The clinical importance
      of IgE antibody concentrations in the interval 0.1-0.34 kU/L in early life in
      relation to allergy development is poorly evaluated. OBJECTIVE: To assess the
      relevance of low specific IgE (s-IgE) to hen's egg, cow's milk and peanut at 6
      months of age for development of sensitization and allergy-related disease during
      early childhood. METHODS: s-IgE concentrations to relevant allergens from blood
      samples taken at 6 months and 1, 2 and 5 years from children in the prospective
      ALADDIN cohort were divided into three categories: non-sensitized (<0.1 kU/L),
      low sensitized (0.1-0.34 kU/L) and sensitized (>=0.35 kU/L) and allergy-related
      disease assessed. RESULTS: A total of 372 children were included in this study.
      Compared with non-sensitized children at 6 months of age, children with low
      levels of allergen specific IgE (0.1-0.34 kU/L) to food allergens, especially to
      egg, at 6 months of age were associated with development of sensitization to
      aeroallergens at 5 years of age (10/14 [71%] vs 39/250 [15%]). In addition,
      children with low levels to egg or milk at 6 months were more often sensitized to
      the respective allergen at 1 year of age and, regarding low levels to egg, also
      to the development of eczema (6/18 [33%] vs 29/292 [10%]). CONCLUSION & CLINICAL
      RELEVANCE: IgE antibody concentrations in the interval 0.1-0.34 kU/L to food
      allergens in infancy seem to increase the probability of sensitization to
      aeroallergens and, regarding low levels to egg, also of eczema during early
      childhood. Thus, IgE levels during the first year of life, although below 0.35
      kU/L, can provide additional allergy-related prognostic information.

PMID- 30204274
TI  - Adaptation of myocardial twist in the remodelled athlete's heart is not related
      to cardiac output.
AB  - NEW FINDINGS: What is the central question of this study? What is the role of
      heart muscle function in the increased output of remodelled, larger hearts? What
      is the main finding and its importance? The greater stroke volume of endurance
      athletes is not associated with enhanced function of the heart muscle (i.e. left
      ventricular twist, torsion and twist-to-shortening) in normal and low-oxygen
      environments. These data indicate that, in the process of cardiac adaptation,
      left ventricular twist may play an important role that is not related to
      generating a larger output. Since enlarged hearts with low output can develop in
      disease, the present findings may influence the future interpretation of heart
      muscle function in patients. ABSTRACT: Despite increased stroke volume (SV),
      'athlete's heart' has been proposed to have a similar left ventricular (LV)
      muscle function - as represented by LV twist - compared with the untrained state.
      However, the underpinning mechanisms and the associations between SV/cardiac
      output and LV twist during exercise are unknown. We hypothesised that endurance
      athletes would have a significantly lower twist-to-shortening ratio (TwSR, a
      parameter that relates twist to the shortening of heart muscle layers) at rest,
      but significantly greater LV muscle function during exercise. Eleven endurance
      trained male runners and 13 untrained males were tested at rest and during supine
      cycling exercise in normoxia and hypoxia (increased cardiac output but unaltered
      SV). Despite the expected cardiac remodelling in endurance athletes, LV twist,
      torsion, TwSR, strain and strain rate ('LV systolic mechanics') did not differ
      significantly between groups (P > 0.05). Structural remodelling, as per relative
      wall thickness, and LV twist did not correlate (r2  = 0.04, P = 0.33). In
      normoxia and hypoxia, exercise increased LV systolic mechanics in both groups (P
      < 0.001), but with different relationships to SV and cardiac output. Conversely
      to our hypothesis, hearts of different size had similar LV systolic mechanics,
      suggesting that similar twist, torsion and TwSR at rest and during exercise
      irrespective of cardiac output may be an important mechanism in healthy hearts.
      We hypothesise that the regulatory 'purpose' of LV twist may be related to the
      sensing of maximal cardiac myofibre stress, which may act as a biologically
      purposeful limiter to contraction.

PMID- 30204273
TI  - Total Synthesis of (-)-Cylindrocyclophane F: A Yardstick for Probing New
      Catalytic C-C Bond-Forming Methodologies.
AB  - A short and efficient total synthesis of the C2 -symmetric (-)-cylindrocyclophane
      F is presented, using a cross olefin metathesis dimerization strategy for
      construction of the [7,7]-paracyclophane macrocycle. The synthesis of the
      dimerization building block includes a Pd-catalyzed sp3 -sp2 Negishi cross
      coupling of a sterically hindered Zn-reagent with an aromatic triflate, an
      enantiospecific Zn-catalyzed sp3 -sp3 cross coupling of an alpha-hydroxy ester
      triflate with a Grignard reagent and the application of an enantioselective Rh
      catalyzed C-allylation of an electron rich arene.

PMID- 30204275
TI  - Nurses' experiences of working in rural hospitals: An integrative review.
AB  - AIM: To critically analyse the international literature describing the
      experiences of nurses working in rural hospitals. BACKGROUND: Nursing shortages
      in rural areas is an ongoing issue. Given the significant role nurses play in the
      delivery of rural health care, a sufficient workforce is essential. However,
      maintaining this workforce is challenging. Understanding the experiences of
      nurses working in rural hospitals is essential to inform strategies around job
      satisfaction and staff retention. EVALUATION: An integrative review was
      conducted. Six primary sources were included related to the experiences of nurses
      working in rural hospitals. RESULTS: Four themes emerged, namely: (a)
      Professional Development; (b) Workplace stressors; (c) Teamwork; and (d)
      Community. CONCLUSION: There is a need for further research exploring the
      experiences of nurses working in rural hospitals and its impact on job
      satisfaction, turnover intention and patient safety. IMPLICATIONS FOR NURSING
      MANAGEMENT: This review highlights some key issues impacting nurses' working in
      rural hospitals. This understanding can be used by nurse managers to inform
      strategies for recruitment and retention of nurses in these areas.

PMID- 30204276
TI  - Hypothalamic DNA methylation in rats with dihydrotestosterone-induced polycystic
      ovary syndrome: effects of low-frequency electro-acupuncture.
AB  - NEW FINDINGS: What is the central question of this study? What is the role of
      hypothalamic DNA methylation in the development of polycystic ovary syndrome
      (PCOS) and the response to electro-acupuncture treatment. What is the main
      finding and its importance? Global DNA methylation and expression of DNA
      methyltransferases (DNMTs) were increased in PCOS-like rats, and electro
      acupuncture (EA) decreased global DNA methylation and DNMT3b expression.
      Pyrosequencing showed that the DNA methylation of some PCOS candidate genes was
      changed in the PCOS and PCOS+EA groups, suggesting that hypothalamic DNA
      methylation plays an important role in the development of PCOS and in mediating
      the effects of electro-acupuncture treatment. ABSTRACT: Polycystic ovary syndrome
      (PCOS) is a common reproductive and endocrine disease of unknown aetiology.
      Recently, epigenetic studies focusing on DNA methylation in PCOS have received
      much attention, but the mechanisms are still unclear. In the present study, we
      used the 5alpha-dihydrotestosterone-induced PCOS-like rat model and treated the
      rats with electro-acupuncture (EA). Rats were randomly divided into four groups -
      controls, diet-induced obesity, PCOS and PCOS+EA. We examined the reproductive,
      metabolic and behavioural phenotypes, validated the effect of EA, and explored
      the role of hypothalamic DNA methylation by analysing the methylation of global
      DNA and selected candidate genes. The PCOS rats presented with reproductive
      dysfunctions such as lack of regular oestrous cyclicity, metabolic disorders such
      as increased body weight and insulin resistance, and depression and anxiety-like
      behaviours. EA improved the reproductive functions, decreased body weight and
      improved experimental depressive behaviour. Furthermore, global DNA methylation
      and the expression of DNA methyltransferases (DNMTs) were increased in PCOS rats
      compared to the control group, and EA decreased the global DNA methylation and
      the expression of DNMT3b. In addition, pyrosequencing showed that the DNA
      methylation of certain CpG sites in targeted genes (Plcg1, Camk2b, Esr2 and Pgr)
      was increased in the PCOS group, but the DNA methylation of Camk2b and Ar was
      decreased after EA treatment. These results indicate that hypothalamic DNA
      methylation might be correlated with the development of PCOS and that EA has an
      effect on hypothalamic DNA methylation in PCOS rats.

PMID- 30204277
TI  - Clinical and demographic characteristics of fatal anaphylaxis in Spain (1998
      2011): A comparison between a series from the hospital system and a national
      forensic series.
AB  - BACKGROUND: Reports of fatal anaphylaxis remain scarce because of the rarity of
      the condition and the fact that information is limited to a few countries.
      OBJECTIVE: Our objective was to investigate clinical and demographic
      characteristics and the causes of fatal anaphylaxis in Spain using two databases
      of cases of fatal anaphylaxis. METHODS: We analysed fatal anaphylaxis in a series
      from the Spanish hospital system and a series from the National Institute of
      Toxicology and Forensic Sciences (Instituto Nacional de Toxicologia y Ciencias
      Forenses [INTCF]), which predominantly comprise extrahospital deaths. Deaths from
      the Spanish hospital system were retrieved from among all deaths occurring during
      1998-2011 using codes related to anaphylaxis. Deaths due to anaphylaxis in the
      INTCF database during the same period were retrieved by 2 allergists, who
      identified cases in which anaphylaxis was a possible cause of death. A logistic
      regression model was constructed to predict the characteristics of fatal
      anaphylaxis in each database. RESULTS: The incidence of death by anaphylaxis in
      Spain using both databases was 0.25 (95% CI, 0.24-0.26) deaths per million person
      years. The most frequent causes of death in the hospital system were drugs
      (46.1%), unknown causes (40.0%), and foods (10.4%); in the INTCF, the most common
      causes of death were drugs (47.2%), insect stings (30.6%), and foods (11.1%). The
      logistic regression model showed that fatal anaphylaxis due to unknown causes (OR
      15.2, 95% CI 1.8-129.8) was more likely in the hospital database, whereas insect
      stings (OR 100, 95% CI 10-833.3) and previous atopic comorbidity (OR 15.2, 95% CI
      6.3-33.3) were more likely in the INTCF database. CONCLUSIONS & CLINICAL
      RELEVANCE: The estimated frequency of fatal anaphylaxis in Spain was among the
      lowest reported. Future studies of fatal anaphylaxis should use databases from
      different origins in order to show the considerable heterogeneity in this type of
      death.

PMID- 30204278
TI  - Functional carbohydrate binding modules identified in evolved dits from
      siphophages infecting various Gram-positive bacteria.
AB  - With increasing numbers of 3D structures of bacteriophage components, combined
      with powerful in silico predictive tools, it has become possible to decipher the
      structural assembly and associated functionality of phage adhesion devices.
      Recently, decorations have been reported in the tail and neck passage structures
      of members of the so-called 936 group of lactococcal siphophages. In the current
      report, using bioinformatic analysis we identified a conserved carbohydrate
      binding module (CBM) among many of the virion baseplate Dit components, in
      addition to the CBM present in the 'classical' receptor binding proteins (RBPs).
      We observed that, within these so-called 'evolved' Dit proteins, the identified
      CBMs have structurally conserved folds, yet can be grouped into four distinct
      classes. We expressed such modules in fusion with GFP, and demonstrated their
      binding capability to their specific host using fluorescent binding assays with
      confocal microscopy. We detected evolved Dits in several phages infecting various
      Gram-positive bacterial species, including mycobacteria. The omnipresence of CBM
      domains in siphophages indicates their auxiliary role in infection, as they can
      assist in the specific recognition of and attachment to their host, thus ensuring
      a highly efficient and specific phage-host adhesion process as a prelude to DNA
      injection.

PMID- 30204279
TI  - High Catalytic Activity of C60 Pdn Encapsulated in Metal-Organic Framework UiO
      67, for Tandem Hydrogenation Reaction.
AB  - Metal nanoparticles (NPs) stabilized by MOFs are very promising for catalysis,
      whereas introduction of C60 into MOFs has been very rarely used, and there was no
      report for their cooperative catalysis in organic syntheses. In this work, C60
      @UiO-67 was synthesized by a one-pot method, so that C60 is uniformly distributed
      on UiO-67 in molecular form. Pd NPs coordinating with C60 have been successfully
      embedded into the framework. The obtained multifunctional C60 Pdn @UiO-67
      catalyst exhibits remarkable synergistic catalytic activity in cascade reactions
      under mild conditions, where UiO-67 affords Lewis acidity and C60 Pdn offers
      higher hydrogenation activity relative to solely Pd NPs.

PMID- 30204280
TI  - Growth differentiation factor-15 is not modified by sacubitril/valsartan and is
      an independent marker of risk in patients with heart failure and reduced ejection
      fraction: the PARADIGM-HF trial.
AB  - AIMS: Growth differentiation factor-15 (GDF-15) is associated with adverse
      prognosis in cardiovascular (CV) and non-CV diseases. We evaluated the
      association of GDF-15 with CV and non-CV outcomes in the PARADIGM-HF trial.
      METHODS AND RESULTS: In 1935 patients with heart failure and reduced ejection
      fraction (HFrEF) in PARADIGM-HF, median GDF-15 values were elevated and similar
      in sacubitril/valsartan and enalapril patients (1626 ng/L and 1690 ng/L,
      respectively). Diabetes, age, creatinine, high-sensitive troponin T, N-terminal
      pro-B-type natriuretic peptide, and New York Heart Association class III/IV were
      most strongly associated with elevated GDF-15 values (all P < 0.001) (adjusted R2
      = 0.3857). Baseline GDF-15 and changes in GDF-15 at both 1 month and 8 months
      (log-transformed) were associated with subsequent mortality and CV events. Each
      20% increment in baseline GDF-15 value was associated with a higher risk of
      mortality [adjusted hazard ratio (HR) 1.13, 95% confidence interval (CI) 1.08
      1.18, P < 0.001], the combined endpoint of CV death or hospitalization for heart
      failure (adjusted HR 1.09, 95% CI 1.05-1.14, P < 0.001) and heart failure death
      (adjusted HR 1.16, 95% CI 1.05-1.28, P < 0.001). Changes in GDF-15 were not
      influenced by assigned therapy (all P-values >= 0.1). CONCLUSION: In patients
      with ambulatory HFrEF, GDF-15 is not modified by sacubitril/valsartan and is
      strongly associated with mortality and CV outcomes, suggesting that GDF-15 is a
      marker of poor outcomes in these patients. CLINICAL TRIAL REGISTRATION:
      ClinicalTrials.gov Identifier NCT01035255.

PMID- 30204281
TI  - Self-Assembly of Perovskite Crystals Anchored Al2 O3 -La2 O3 Nanofibrous
      Membranes with Robust Flexibility and Luminescence.
AB  - Inorganic luminescent materials as one of the important high-performance
      materials are widely used for industry and scientific research, mainly owing to
      their outstanding luminescence properties. However, inorganic luminescent
      materials are typically brittle and inelastic, which greatly limit their use in
      practical applications, particularly in flexible optoelectronic devices. In this
      work, it is shown that "plum-pudding" like CsPbBr3 /Cs4 PbBr6 perovskite crystals
      anchor onto Al2 O3 -La2 O3 (CCAL) nanofibrous membranes, which are synthesized
      via a facile electrospinning and subsequent supersaturated recrystallization
      process. The as-synthesized CCAL membranes exhibit outstanding mechanical
      flexibility and luminescence properties. Meanwhile, the crystal structure and
      luminous performance of the CCAL membranes are regulated by different molar
      ratios of CsBr/PbBr2 . The photoluminescence reaches a maximum value for the CCAL
      membranes produced with a CsBr/PbBr2 ratio of 1, and shows a narrow emission line
      width of 18 nm. Furthermore, the potential applications of the CCAL nanofibrous
      membranes in green light devices through a remote nanofibrous membranes packaging
      approach are demonstrated. A pure green emission is achieved with the Commission
      Internationale de L'Eclairage color coordinates of (0.28, 0.65). This facile
      strategy would open a new avenue to flexible inorganic luminescent materials for
      the lighting and backlight display industries.

PMID- 30204282
TI  - Cubane-Type [Mo3 S4 M] Clusters with First-Row Groups 4-10 Transition-Metal
      Halides Supported by C5 Me5 Ligands on Molybdenum.
AB  - A synthetic protocol was developed for a series of cubane-type [Mo3 S4 M]
      clusters that incorporate halides of first-row transition metals (M) from Groups
      4-10. This protocol is based on the anionic cluster platform [Cp*3 Mo3 S4 ]- ([1]
      ; Cp*=eta5 -C5 Me5 ), which crystallizes when K(18-crown-6) is used as the
      counter cation. Treatment of in situ-generated [1]- with such transition-metal
      halides led to the formation of [Mo3 S4 M] clusters, in which the M/halide ratio
      gradually changes from 1:2 to 1:1.5 and to 1:1, when moving from early to late
      transition metals. This trend suggests a tendency for early transition metals to
      tolerate higher oxidation states and adopt larger ionic radii relative to late
      transition metals. The properties of the [Mo3 S4 Fe] cluster 6 a were
      investigated in detail by using 57 Fe Mossbauer spectroscopy and computational
      methods.

PMID- 30204283
TI  - Visualizing cellular stress: A hypothesis-driven confocal laboratory exercise to
      identify compounds that activate heat shock factor binding at Hsp70 loci.
AB  - Exposure of organisms to high temperatures and various chemical and physical
      stressors can cause protein misfolding and aggregation. In turn, this can disrupt
      the functions of proteins, threatening both development and homeostasis. To
      overcome this, cells can initiate the highly conserved heat shock (HS) stress
      response pathway. In eukaryotes, this is a coordinated cellular response, in
      which the master HS activator, heat shock factor (HSF), is rapidly recruited to
      the HS protein genes, and triggers the recruitment of additional coactivator
      proteins that facilitate gene expression. This results in the production of HS
      proteins that function as nuclear and cytosolic molecular chaperones, to promote
      refolding of proteins and prevent aggregation and increase protein degradation
      pathways. Here, we describe a laboratory exercise in which students visualize and
      quantify Green Fluorescent Protein (GFP)-tagged HSF binding to the HS protein
      genes in living Drosophila salivary gland nuclei as an output of chemically
      induced protein misfolding. Students are assigned an array of chemicals, and
      using the scientific literature, predict impacts of these chemicals on protein
      folding. Students then test the effects of their chemicals by measuring GFP
      tagged HSF binding to the HS genes in salivary glands using confocal microscopy.
      Designed for junior and senior level students in a cell/molecular biology course,
      this is a two-part lab, in which student work closely with an instructor to help
      familiarize them with developing hypotheses supported by scientific literature
      and testing these hypotheses by quantitating the levels of GFP-HSF binding, using
      confocal microscopy of living Drosophila cells. (c) 2018 International Union of
      Biochemistry and Molecular Biology, 46(5):445-452, 2018.

PMID- 30204284
TI  - Photodynamics and Luminescence of Mono- and Tri-Nuclear Lanthanide Complexes in
      the Gas Phase and in Solution.
AB  - Lanthanide ions (DyIII , EuIII ) are stabilized by coordination with two Schiff
      base ligands in compounds [Dy{H3 L}2 ](NO3 )(EtOH)(H2 O)8 (1) and [Eu{H3 L}2
      ](NO3 )(H2 O)8 (3) (H4 L, 2,2'-{[(2-aminoethyl)imino]bis[2,1-ethanediyl
      nitriloethylidyne]}bis-2-hydroxy-benzoic acid). The latter is reported here for
      the first time. Both luminescence and ultrafast photodynamics after
      photoexcitation via a ligand absorption band (~400 nm) have been studied. In
      solution, only the [Eu{H3 L}2 ]+ ([3]+ ) complex displays the typical lanthanide
      emission lines, whereas in gas phase both, [Dy{H3 L}2 ]+ ([1]+ ) and [3]+ , show
      their corresponding transitions depending on excitation energy. The ultrafast
      excited state dynamics, obtained in gas phase and in solution, are assigned to
      excited state intramolecular proton transfer processes in the ligands. The
      antenna ligand moiety of these complexes provides pockets for stabilization of
      two MnII ions so that we additionally investigated the photophysical behavior of
      the corresponding tri-nuclear (NHEt3 )2 [Ln{MnL}2 ](ClO4 )(H2 O)2 (Ln=DyIII ,
      EuIII ) compounds (2, 4). Interestingly, the related complexes do not show
      lanthanide emission, neither in solution nor in gas phase. Transient data in
      solution and gas phase suggests an efficient quenching of the ligand's
      electronically excited state by strong interaction with the MnII ions. This
      effect could possibly be developed further into a design principle for
      luminescence-based sensing devices for metal cations.

PMID- 30204285
TI  - Economic injury levels and sequential sampling plans for control decision-making
      systems of Bemisia tabaci biotype B adults in watermelon crops.
AB  - BACKGROUND: Decision-making systems are essential parts of integrated pest
      management programs. The whitefly Bemisia tabaci (Hemiptera: Aleyrodidae) is a
      major pest of many crops, including watermelon (Citrullus lanatus), the second
      most consumed fruit worldwide. However, there are still no studies on decision
      making systems for B. tabaci on this crop. Thus, we aim to determine a decision
      making system to control B. tabaci biotype B on watermelon crops. RESULTS: The
      highest densities of B. tabaci biotype B reduced the yield of watermelon crops by
      up to 56%. Watermelon plants were more susceptible to the pest at the vegetative
      stage than at the reproductive stage. The economic injury levels of B. tabaci
      biotype B when watermelon prices were low, average, and high were respectively,
      0.52, 0.21 and 0.13 adults leaf-1 at the vegetative stage, and 1.69, 0.69 and
      0.44 adults leaf-1 at the reproductive stage. The sequential plans reached the
      same decisions as the conventional plan, and reduced the time and cost of
      sampling by up to 92.68%. CONCLUSION: The decision-making systems determined in
      this study enable an expedited and proper decision to be made for controlling B.
      tabaci, biotype B and can be used in different price situations for watermelon
      and in crops at different phenological stages. (c) 2018 Society of Chemical
      Industry.

PMID- 30204286
TI  - Isolation of CarE genes from the Chinese white pine beetle Dendroctonus armandi
      (Curculionidae: Scolytinae) and their response to host chemical defense.
AB  - BACKGROUND: Bark beetles rely on detoxifying enzymes to resist the defensive
      terpenoids of their host trees. Research on carboxylesterases (CarEs) has focused
      on their multiple functions in the metabolic detoxification of pesticides and
      plant allelochemicals, drug resistance, and juvenile hormone and pheromone
      degradation. RESULT: We identified eight new CarE genes in the Chinese white pine
      beetle (Dendroctonus armandi) and carried out bioinformatics analysis on the
      deduced full-length amino acid sequences. Differential transcript levels of CarE
      genes were observed between sexes; within these levels, significant differences
      were found among the different development stages, and between insects fed on the
      phloem of Pinus armandi and exposed to five stimuli [(-)-alpha-pinene, (-)-beta
      pinene, (+)-3-carene, limonene and turpentine] at 8 and 24 h. CONCLUSION:
      Transcription levels of CarE genes suggest some relationship with the
      detoxification of terpenoids released by host trees. The functions of bark beetle
      esterase are mainly in hydrolyzing the host chemical defense and degrading
      odorant molecules during host selection and colonization. (c) 2018 Society of
      Chemical Industry.

PMID- 30204287
TI  - Cognitive deficits and psychopathological symptoms among children with
      medulloblastoma.
AB  - Children with medulloblastoma (MB) are predisposed for negative cognitive
      sequela, which has been widely identified in this population. The purpose of the
      present study was to explore cognitive deficits and psychopathological symptoms
      and analyse their relation among MB survivors. The Wechsler Intelligence Scale
      for Children and the Mini International Neuropsychiatric Interview (MINI-KID) was
      administered to 34 MB survivors to measure cognitive functioning and
      psychopathological symptoms. The MB survivors had lower global IQ (86.41 [79.70
      93.13]) compared with the control population mean. We found impaired functioning
      in all IQ subscales in the MB survivors group, of which processing speed (84.15
      [77.71-90.58]) was the most affected. Higher radiation dose and high-dose
      chemotherapy with stem cell rescue were significantly associated factors for
      lowered global IQ, while age at diagnosis, sex and time period from diagnosis
      were not significantly associated. Compulsive disorder, generalised anxiety,
      separation anxiety and posttraumatic stress disorder were significantly more
      prevalent in the MB survivor group than a group of 46 control participants. No
      correlation was found between the cognitive deficits and the psychopathological
      symptoms. Our results identify that MB survivors suffer from cognitive and
      psychopathological impairments, and these could exist independently from each
      other.

PMID- 30204288
TI  - Is Raman Optical Activity Spectroscopy Sensitive to beta-Turns in Proteins?
      Secondary Structure and Side-Chain Dependence.
AB  - beta-turns are essential for the structure and function of proteins. The
      spectroscopic technique Raman optical activity (ROA) has been suggested to be
      sensitive to such structural elements of proteins in solution. Three spectral
      features have been reported to mark beta-turns in protein ROA spectra: being a
      negative band at 1220 cm-1 , positive intensity around 1290 cm-1 and negative
      intensity around 1340-1380 cm-1 . In this work, density functional theory
      calculations demonstrated that these assignments are inaccurate as these spectral
      regions are not robust and sense the exact secondary structure surrounding the
      beta-turn as well. Furthermore, it was demonstrated that the amino acid side
      chains affect the exact ROA patterns which can direct future research to perform
      a systematic analysis of the contributions of the side-chains.

PMID- 30204289
TI  - REtrieval And cure of Chronic Hepatitis C (REACH): Results of micro-elimination
      in the Utrecht province.
AB  - BACKGROUND: The Netherlands is one of the six European countries considered on
      track to eliminate hepatitis C virus by 2030. To achieve this goal, continuous
      efforts have to be put into designing efficient case-finding strategies,
      including the retrieval of previously diagnosed hepatitis C virus-infected who
      are lost to follow-up. AIMS: To trace and treat all lost to follow-up hepatitis C
      virus patients in the Utrecht region and create an efficient retrieval strategy
      that can be used in future (national) retrieval initiatives. METHODS: Positive
      hepatitis C virus diagnostic tests (anti-hepatitis C virus IgG or hepatitis C
      virus-RNA) from the laboratory of all four hospitals and one central laboratory
      for primary care diagnostics in the province of Utrecht from 2001 to 2015 were
      linked to clinical records. Untreated patients with available contact information
      were deemed eligible for retrieval and invited for reevaluation with (virology)
      blood tests, fibroscan measurement and possible direct-acting antiviral therapy.
      MAIN RESULTS: After screening all hepatitis C virus diagnostics, 1913 chronic
      hepatitis C virus-infected were identified of which 14.1% (n = 269) were invited
      back into care. Overall, 17.4% was traced with the highest yield (28.3%) in those
      who lived in the Utrecht province. Through renewed patient assessments, 42
      chronic hepatitis C virus infections were re-identified (76% with a history of
      intravenous drug use, 24% with Metavir F3-F4). Until now, 59% has either
      scheduled or initiated direct-acting antiviral therapy. CONCLUSION: The retrieval
      of previously diagnosed hepatitis C virus patients through screening of
      laboratory diagnostics from the past is feasible and should be pursued for
      further control and reduction of hepatitis C virus infection. Retrieval is most
      successful when performed regionally. LAY SUMMARY: To completely eliminate
      chronic hepatitis C virus (HCV) infection and prevent complications, undiagnosed
      and also previously diagnosed but lost to follow-up (LFU) HCV patients have to be
      brought (back) into care for therapy. Retrieval of LFU HCV patients through
      screening of laboratory diagnostics from the past is feasible and most successful
      when performed regionally.

PMID- 30204290
TI  - A Single Amino Acid Substitution in Therminator DNA Polymerase Increases
      Incorporation Efficiency of Deoxyxylonucleotides.
AB  - Deoxyxylonucleic acid (dxNA) is a synthetic polymer that might have potential for
      heredity and evolution. Because of dxNA's unusual backbone geometry, sequence
      information stored in it is presumed to be inaccessible to natural nucleic acids
      or proteins. Despite a large structural similarity with natural nucleotides,
      incorporation of 2'-deoxyxylonucleotides (dxNTs) through the action of
      polymerases is limited. We present the identification of a mutant of the DNA
      polymerase Therminator with increased tolerance to deoxyxylose-induced backbone
      distortions. Whereas the original polymerase stops after incorporation of two
      consecutive dxNTs, the mutant is able to catalyse the extension of incorporated
      dxNTs with 2'-deoxyribonucleotides (dNTs) and the incorporation of up to four
      dxNTs alternates with dNTs, thereby translocating a highly distorted double helix
      throughout the entire polymerase. A single His-to-Arg substitution very close to
      the catalytic site residues is held to be responsible for interaction with the
      primer phosphate groups and for stabilizing nucleotide sugar-induced distortions
      during incorporation and translocation.

PMID- 30204291
TI  - Unraveling Substrate Specificity and Catalytic Promiscuity of Aspergillus oryzae
      Catechol Oxidase.
AB  - Catechol oxidases and tyrosinases are coupled binuclear copper enzymes that
      oxidize various o-diphenolic compounds to corresponding o-quinones. Tyrosinases
      have an additional monooxygenation ability to hydroxylate monophenol to o
      diphenol. It is still not clear what causes the difference in the catalytic
      activities. We solved a complex structure of Aspergillus oryzae catechol oxidase
      with resorcinol bound into the active site. Catalytic activity of A. oryzae
      catechol oxidase was studied, for the first time, by high-resolution FT-ICR mass
      spectrometry to shed light on the reaction mechanism. The enzyme was also found
      to catalyze monooxygenation of small phenolics, which provides a novel
      perspective for the discussion of differences in the catalytic activity between
      tyrosinases and catechol oxidases. According to the results, two binding modes
      for resorcinol are suggested and a reaction mechanism for coupled binuclear
      copper enzymes is discussed.

PMID- 30204292
TI  - Synthesis of Functionalized Cyclopropanes from Carboxylic Acids by a Radical
      Addition-Polar Cyclization Cascade.
AB  - Herein, we describe the development of a photoredox-catalyzed decarboxylative
      radical addition-polar cyclization cascade approach to functionalized
      cyclopropanes. Reductive termination of radical-polar crossover reactions between
      aliphatic carboxylic acids and electron-deficient alkenes yielded carbanion
      intermediates that were intercepted in intramolecular alkylations with alkyl
      chlorides appended to the alkene substrate. The mild conditions, which make use
      of a readily available organic photocatalyst and visible light, were demonstrated
      to be amenable to a broad range of structurally complex carboxylic acids and a
      wide variety of chloroalkyl alkenes, demonstrating exquisite functional group
      tolerance.

PMID- 30204293
TI  - Nucleophilic versus Electrophilic Reactivity of Bioinspired Superoxido Nickel(II)
      Complexes.
AB  - The formation and detailed spectroscopic characterization of the first biuret
      containing monoanionic superoxido-NiII intermediate [LNiO2 ]- as the Li salt [2;
      L=MeN[C(=O)NAr)2 ; Ar=2,6-iPr2 C6 H3 )] is reported. It results from oxidation of
      the corresponding [Li(thf)3 ]2 [LNiII Br2 ] complex M with excess H2 O2 in the
      presence of Et3 N. The [LNiO2 ]- core of 2 shows an unprecedented nucleophilic
      reactivity in the oxidative deformylation of aldehydes, in stark contrast to the
      electrophilic character of the previously reported neutral Nacnac-containing
      superoxido-NiII complex 1, [L'NiO2 ] (L'=CH(CMeNAr)2 ). According to density
      functional theory (DFT) calculations, the remarkably different behaviour of 1
      versus 2 can be attributed to their different charges and a two-state reactivity,
      in which a doublet ground state and a nearby spin-polarized doublet excited-state
      both contribute in 1 but not in 2. The unexpected nucleophilicity of the
      superoxido-NiII core of 2 suggests that such a reactivity may also play a role in
      catalytic cycles of Ni-containing oxygenases and oxidases.

PMID- 30204295
TI  - Retraction.

PMID- 30204294
TI  - The many faces of genetic contributions to temporomandibular joint disorder: An
      updated review.
AB  - OBJECTIVES: The aim was to review the literature regarding genetic contributions
      to temporomandibular joint disorder (TMD) after our 2008 publication. SETTING AND
      SAMPLE POPULATION: Literature review. MATERIAL AND METHODS: PubMed and MEDLINE
      were used to obtain literature in any language regarding genes and TMD, using the
      keywords "temporomandibular joint disorder" and "temporomandibular joint
      dysfunction" for studies published from 2009 to 2017. RESULTS: In our search, 274
      studies were found. We excluded 76 studies from animal models, 22 studies that
      were in vitro and 120 reports that were not cohort or case-control studies. Of
      the 274 results, 56 articles were selected for this review. Genes that are
      suggested to contribute to TMD included the ones related to disc and bone
      alterations as well as pain sensation. CONCLUSION: Currently, no evidence of
      associated genetic variants, which can determine the development of TMD in
      individuals, could be translated to novel clinical management and public health
      strategies for patients suffering from TMD.

PMID- 30204296
TI  - Evolution of type 2 diabetes mellitus treatment approaches.

PMID- 30204297
TI  - Modeling Chronic Graft Versus Host Disease in Mice Using Allogeneic Bone Marrow
      and Splenocyte Transfer.
AB  - This unit describes a method for allogeneic bone marrow and splenocyte transfer
      for the modeling of chronic graft versus host disease (cGVHD) in mice.
      Preclinical models provide clinically relevant platforms for mechanistic and
      therapeutic studies that may inform the treatment of patients suffering from
      cGVHD, a common and potentially severe complication of allogeneic hematopoietic
      stem cell transplantation (alloHSCT). Most murine models of cGVHD depend on the
      transfer of major histocompatibility complex (MHC)-mismatched bone marrow and
      whole splenocytes (or purified T cells) into an irradiated recipient. The bone
      marrow contains hematopoietic stem and progenitor cells necessary to reconstitute
      the irradiated host hematopoietic system, while splenocytes contain T cells that
      mediate cGVHD. Of note, specific mouse strains, splenocyte dose, bone marrow
      quantity, and irradiation doses vary widely across different cGVHD models. Here
      we describe donor bone marrow and splenocyte preparation, recipient irradiation
      and intravenous injection of donor cells, and clinical monitoring for disease
      emergence and progression. (c) 2018 by John Wiley & Sons, Inc.

PMID- 30204299
TI  - Association of gamma-glutamyl transferase and alanine aminotransferase with type
      2 diabetes mellitus incidence in middle-aged Japanese men: 12-year follow up.
AB  - AIMS/INTRODUCTION: To prospectively investigate whether simultaneous elevation of
      gamma-glutamyl transferase (GGT) and alanine aminotransferase (ALT) is associated
      with the increase of type 2 diabetes mellitus incidence independent of alcohol
      drinking, body mass index and triglycerides. METHODS: A total of 2,775 Japanese
      male workers who had no history of type 2 diabetes mellitus were followed. High
      GGT and ALT were defined as the top tertiles (GGT cutpoint: 49 IU/L, ALT
      cutpoint: 28 IU/L). Three groups were created using these dichotomized GGT and
      ALT cutpoints: both low, either high or both high. Multivariable Cox proportional
      hazards models were carried out adjusted for potential confounding factors.
      RESULTS: A total of 276 type 2 diabetes mellitus cases were identified during 12
      years (27,040 person-years) of follow up. Participants with simultaneously
      elevated GGT and ALT had a significantly higher incidence of type 2 diabetes
      mellitus, even after adjustment for fasting insulin and fasting blood glucose
      compared with the group without GGT or ALT elevation. Similar associations were
      observed in non- or light-to-moderate alcohol drinkers, as well as in
      participants with normal weight. However, the association was weaker in
      participants with triglycerides <150 mg/dL. We then evaluated whether the
      addition of GGT and ALT would improve the prediction of type 2 diabetes mellitus
      incidence, and found that their inclusion significantly increased the C
      statistic, net reclassification improvement and integrated discrimination
      improvement. CONCLUSIONS: Simultaneous elevation of GGT and ALT was significantly
      associated with type 2 diabetes mellitus incidence, independent of potential
      confounding factors, including alcohol drinking and obesity, although the
      association might require concomitant elevation of triglycerides. Inclusion of
      GGT and ALT improved type 2 diabetes mellitus risk prediction.

PMID- 30204298
TI  - Chelated Diborenes and Their Inverse-Electron-Demand Diels-Alder Reactions with
      Dienes.
AB  - A doubly base-stabilised diborane based on a benzylphosphine linker was prepared
      by a salt elimination reaction between 2-LiC6 H4 CH2 PCy2 ?Et2 O and B2 Br4 .
      This compound was reduced with KC8 to its corresponding diborene, with the
      benzylphosphine forming a five-membered chelate. The diborene reacts with
      butadiene, 2-trimethylsiloxy-1,3-butadiene, and isoprene to form 4,5
      diboracyclohexenes, which interconvert between their 1,1- (geminal) and 1,2-
      (vicinal) chelated isomers. The 1,1-chelated diborene undergoes a halide
      catalysed isomerisation into its thermodynamically favoured 1,2-isomer, which
      undergoes Diels-Alder reactions more slowly than the kinetic product.

PMID- 30204300
TI  - Dual-Channel Photostimulation for Independent Excitation of Two Populations.
AB  - Manipulation of defined neurons using excitatory opsins, including
      channelrhodopsin, enables studies of connectivity and the functional role of
      these circuit components in the brain. These techniques are vital in the
      neocortex, where diverse neurons are intermingled, and stimulation of specific
      cell types is difficult without the spatial, temporal, and genetic control
      available with optogenetic approaches. Channelrhodopsins are effective for
      mapping excitatory connectivity from one input type to its target. Attempts to
      use multiple opsins to simultaneously map multiple inputs face the challenge of
      partially overlapping light spectra for different opsins. This protocol describes
      one strategy to independently stimulate two comingled inputs in the same brain
      area to assess convergence and interaction of pathways in neural circuits. This
      is highly relevant in the neocortex, where pyramidal neurons integrate excitatory
      inputs from multiple local cell types and long-range corticocortical and
      thalamocortical projections. (c) 2018 by John Wiley & Sons, Inc.

PMID- 30204301
TI  - Multiplexed Metabolic Labeling of Glycoconjugates in Polarized Primary Cerebral
      Cortical Neurons.
AB  - The spatial distribution of cell-surface glycoconjugates in the brain changes
      continuously, reflecting neurophysiology especially in the developing phase, but
      their functions and fates mostly remain unexplored. Their spatiotemporal
      distribution is particularly important in polarized neuronal cells, such as
      cerebral cortical neurons composed of a soma and neurites. In this work, we
      dually labeled sialic acid (Sia5Ac) and N-acetylgalactosamine/glucosamine
      (GalNAc/GlcNAc) by a neurocompatible strategy of metabolic glycan labeling,
      metabolism-by-tissues (MbT), and obtained the multiplexed information on their
      spatiotemporal distribution on polarized cortical neurons. The analyses showed
      the preferentially distinct distribution of each saccharide set at the late
      developmental stage after randomized, heterogeneous distribution at the early
      stage, suggesting that Sia5Ac and GalNAc/GlcNAc are translocated anisotropically
      during neuronal development.

PMID- 30204302
TI  - RNAi Screening: Automated High-Throughput Liquid RNAi Screening in Caenorhabditis
      elegans.
AB  - RNAi is a powerful reverse genetics tool that has revolutionized genetic studies
      in model organisms. The bacteriovorous nematode Caenorhabditis elegans can be
      genetically manipulated by feeding it an Escherichia coli strain that expresses a
      double-stranded RNA (dsRNA) corresponding to a C. elegans gene, which leads to
      systemic silencing of the gene. This unit describes protocols for performing an
      automated high-throughput RNAi screen utilizing a full-genome C. elegans RNAi
      library. The protocols employ liquid-handling robotics and 96-well plates. (c)
      2018 by John Wiley & Sons, Inc.

PMID- 30204303
TI  - Clinical preferences and trends of anti-vascular endothelial growth factor
      treatments for diabetic macular edema in Japan.
AB  - AIMS/INTRODUCTION: To determine the current clinical preferences of anti-vascular
      endothelial growth factor (VEGF) treatment protocols for diabetic macular edema
      (DME) in Japan. MATERIALS AND METHODS: This was a descriptive cross-sectional
      study. Answers to a questionnaire consisting of 16 questions were obtained from
      176 of 278 (63.3%) surveyed ophthalmologists. RESULTS: The results showed that
      81.2% preferred intravitreal injections of anti-VEGF antibodies as the first-line
      therapy. The most important indicators for beginning anti-VEGF therapy were: the
      best-corrected visual acuity in 44.3% and the retinal thickness in 30.7%. In the
      loading phase, 53.4% preferred a single injection, and in the maintenance phase,
      75.0% preferred the pro re nata regimen. Financial limitation (85.8%) was
      reported as the most important difficulty in the treatment. For combination
      therapy with anti-VEGF treatment, panretinal photocoagulation, focal
      photocoagulations and a sub-Tenon steroid injection were preferred. The
      contraindications for anti-VEGF therapy were: prior cerebral infarction (72.7%).
      Regarding the use of both approved anti-VEGF agents in Japan, ranibizumab and
      aflibercept, 39.8% doctors used them appropriately. CONCLUSIONS: Our results
      present the current clinical preferences of anti-VEGF treatment for DME in Japan.
      The best-corrected visual acuity and the retinal thickness are important
      indicators to institute this therapy. The majority of the ophthalmologists use
      anti-VEGF treatment as first-line therapy and prefer the 1 + pro re nata regimen.

PMID- 30204304
TI  - Environmentally and Industrially Friendly Recycling of Platinum Nanoparticles
      Through Electrochemical Dissolution-Electrodeposition in Acid-Free/Dilute Acidic
      Electrolytes.
AB  - A process to recycle platinum from industrial waste, for example, spent catalysts
      from polymer fuel cells and electrolyzers, through potentiodynamic dissolution
      along with potentiostatic electrodeposition in dilute acidic/acid-free baths has
      been explored. During potentiodynamic dissolution, owing to Ostwald ripening,
      redeposition of the dissolved Pt species on source nanoparticles becomes
      significant, leading to lower overall dissolution efficiency. Alternatively, high
      concentrations of Pt-complexing agents (e.g., Cl- ) are required to stabilize
      dissolved species through complex formation. The present process overcomes those
      limitations by removing the dissolved Pt species continuously through
      electrodepositing them in the form of Pt0 on another electrode. Such a process
      significantly promotes the overall reaction kinetics, and an increase in
      dissolution rate by a factor of two or more has been observed in non-complexing
      electrolytes. The process may be implemented for environmentally and industrially
      friendly recycling of Pt in dilute acidic/acid-free baths, thus eliminating the
      additional steps such as electrolyte upconcentration and post-dissolution
      reduction of dissolved Pt species.

PMID- 30204305
TI  - Small Molecules to Target the Selenoprotein Thioredoxin Reductase.
AB  - The selenoprotein thioredoxin reductase (TrxR) enzymes are the only identified
      proteins that maintain thioredoxin (Trx) proteins in a reduced state under
      physiological conditions, and consequently play a pivotal role in the regulation
      of various cellular redox signaling pathways involved in cell differentiation,
      growth, and death. The elevated expression of TrxR enzymes has been observed in
      different types of cancer cells, and this overexpression is of pathological
      significance in maintaining tumor phenotypes, such as uncontrolled proliferation
      and resistance to apoptosis. Herein, we discuss recent advances in the study of
      TrxR, including classic assays of TrxR, the emerging chemical tools of TrxR, and
      small molecules that target TrxR as potential anticancer agents.

PMID- 30204306
TI  - Autoimmune hepatitis exerts a profound, negative effect on health-related quality
      of life: A prospective, single-centre study.
AB  - BACKGROUND AND AIMS: Autoimmune hepatitis is a progressive chronic liver disease.
      Health-related quality of life in autoimmune hepatitis has not attracted much
      attention so far. We prospectively assessed various aspects of health-related
      quality of life in a well characterized group of patients with autoimmune
      hepatitis. METHODS: In total, 140 patients with autoimmune hepatitis (mean age 40
      +/- 17 years) and 170 controls (mean age 36 +/- 14 years) were included. Health
      related quality of life was evaluated with following questionnaires: The Short
      Form (36) Health Survey, Modified Fatigue Impact Score, State-Trait Anxiety
      Inventory and Patient Health Questionnaire-9 assessing depression. RESULTS:
      Patients with autoimmune hepatitis showed a significant impairment of health
      related quality of life in all, but one, domains of The Short Form (36) Health
      Survey. Autoimmune hepatitis was associated with pronounced physical fatigue (P <
      0.001), anxiety (P < 0.001) and depression (P < 0.001). As compared to males,
      female patients demonstrated greater impairment of physical aspects of The Short
      Form (36) Health Survey and Modified Fatigue Impact Score. Twenty-seven patients
      (19%) had moderate (Patient Health Questionnaire-9 >10) and 14 (10%) moderately
      severe depression (Patient Health Questionnaire-9 >15). Depression showed a very
      strong correlation with chronic fatigue (R = 0.68; P < 0.001); physical and
      mental components of The Short Form (36) Health Survey (R = 0.52/0.68
      respectively; P < 0.001) and anxiety (R = 0.47; P < 0.001). There was a trend
      towards better life's quality in patients treated with budesonide in some aspects
      of their health-related quality of life. Duration of the disease, age at
      diagnosis, liver fibrosis and the presence of cirrhosis were not associated with
      health-related quality of life. CONCLUSIONS: Health-related quality of life is
      significantly impaired in patients with autoimmune hepatitis. Depression seems to
      be a dominant symptom affecting their well-being, not associated with clinical
      and biochemical features of the disease.

PMID- 30204308
TI  - American Association of Physicians of Indian Origin (AAPI), Arkansas Chapter.

PMID- 30204307
TI  - Dorsal hypothalamic dopaminergic neurons play an inhibitory role in the
      hypothalamic-pituitary-adrenal axis via activation of D2R in mice.
AB  - AIM: The present study investigated the effects of dorsal hypothalamic dopamine
      (dh-DA) neurons on activation of hypothalamic-pituitary-adrenal (HPA) axis in
      adult male mice. METHODS: Tyrosine hydroxylase-labelled DA neurons, DA content, c
      Fos immune-positive (c-Fos+) cells and CRH expression in paraventricular nuclei
      (PVN), serum CORT and ACTH were examined at 4-, 8-, and 12-hour after a signal
      injection of MPTP (20 mg kg-1 ) respectively. RESULTS: The dh-DA neurons and DA
      content in PVN at 4-hour post-MPTP were reduced with recovery at 12-hour post
      MPTP, while decline of nigrostriatal DA neurons and DA content in striatum
      started from 12-hour post-MPTP. Number of c-Fos+ cells, and CORT/ACTH levels
      increased at 4-hour post-MPTP, followed by recovery at 12-hour post-MPTP. The CRH
      mRNA was elevated at 4-hour post-MPTP, and sustained for over 12 hours. At 2-hour
      post-MPTP, PVN-injection of D2R agonist quinpirole corrected the increases in c
      Fos+ cells, CORT/ACTH and CRH mRNA, but D1R agonist SKF38393 did not. PVN
      injection of D2R antagonist L-sulpiride alone caused increases in c-Fos+ cells,
      CORT/ACTH and CRH mRNA. Similarly, PVN-injection of CB1R agonist WIN552,12
      prevented the increases in c-Fos+ cells and CORT/ACTH rather than CRH mRNA, which
      were blocked by CB1R antagonist AM251. Levels of PKA and CREB phosphorylation in
      PVN were increased at 4-hour post-MPTP, which were blocked by quinpirole, but not
      WIN552,12. PKA inhibitor H89 corrected the increase of CRH mRNA at 8-hour post
      MPTP. CONCLUSION: The activation of dh-DA neurons regulates negatively HPA axis
      through targeting D2Rs of CRH neurons to enhance endocannabinoid release and
      inhibit PKA-CREB pathway.

PMID- 30204309
TI  - The State of Public Health in Arkansas in 2016.

PMID- 30204310
TI  - Preventing Substance Abuse With Data-Driven Coalitions.

PMID- 30204311
TI  - [Montaigne and the experience of falling from his horse].
AB  - Around 1573 or 1574, Michel de Montaigne (1533-1592) suffered afallfrom his
      horse, followed by fainting for two or three hours. He describes the accident in
      the 6th chapter of the second volume of his Essays, from two points of view:
      evocation of the accident itself and description of what he felt during this
      experience that enabled him, somehow, to "be close to death". This text, where
      Montaigne explains one of his intimate experiences, appears as an important light
      on the origins and the nature of his Essays.

PMID- 30204312
TI  - [Bossuet (1627-1704) and medicine, a tutor in anatomy and physiology].
AB  - In 1670, when president Perigny died, Bossuet was nominated by king Louis
      XIVthfor being the tutor of his first son, Louis de France (1661-1711) as the
      Great Dauphin, and he will hold this office, during ten years until 1680, within
      the crown prince's educational team managed by the formidable duke of Montausier.
      In that environment he was induced to write several books ; one of them entitled
      About knowledge of God and oneself, in his chapter II "About the body", depict -
      according to knowledges, ideas and prejudices of that time - the general anatomy
      and what will be later named physiology, the body functions, rather the animal
      than the human ones. He went over the main organs with their summarily
      descriptions and what he understood about their effects, and the main organic
      functions. This is the opportunity for understanding how the)6th century medical
      concepts were assimilated and translated by an unversed person though he was a
      great prelate, a great preacher and a great author.

PMID- 30204313
TI  - [Chateaubriand and contemporary medicine].
AB  - The author reviews the situation of medicine in the time of Chateaubriand, then
      his attitude toward this art and its practitioners, then his own pathology,
      psychological as well as somatic.

PMID- 30204314
TI  - [A medical reading of Nerval's Aurelia].
AB  - The single literary study of Aur6lia of Gerard de Nerval-eliminates the author's
      mental illness expression. We set a clinical analysis that brings to the fore
      some unrecognized aspects of the work.

PMID- 30204315
TI  - [Leopold Chauveau (1870-1940), a doctor, writer, painter and sculptor].
AB  - Leopold Chauveau born in Lyon was a renowned writer during the years 1920-1930,
      then nearly forgotten. He was the son of Augustin Chauveau (1827-1917) the famous
      veterinary who had a leading role in the scientific life in the 19th century.
      Leopold Chauveau was particulary appreciated for his tales for kids. Some of his
      compilations were illustrated by his friend the painter Pierre Bonnard. His
      novels were published by the NRF so he was very closed to Gide, to Martin du
      Gard, to Eugene Dabit partners of this publishing house. At the first he was a
      medecine doctor, house doctor in Paris hospitals, ORL-surgeon, surgeon "beyond
      the fight" on the battle front during the WWI. But at that time greatly moved by
      the slaughter he had seen and by the deaths of his nearest and dearest : his wife
      and two of his four sons, he completely renounced his medical practice. He
      actually became writer, talented illustrator, monsters sculptor... He died
      exhausted during the debacle in 1940. His tales for children are a talk to little
      Renaud (his dead son) beyond the hereafter, they are an outled for one'sorrow.
      All these texts are now studied by specialists, republished, discovered by the
      Japanese. All his books and novels are very sensitive,full of a philo- sophic
      spirit and a delicious imagination. His pictures are outstanding.

PMID- 30204316
TI  - [Dr Vangeon, a.k.a. Henri Gheon, a writer from Brie and associated founder of the
      Nouvelle Revue Francaise].
AB  - A medical doctor graduated in 1901, Henri Vangeon (1875-1944) was early known as
      a writer with the name of Henri Gheon. In poetry, he joined the group of the
      symbolists lead by Mallarme and Verhaeren. His activity grew with publishing
      reponsibility for the review 'Ermitage, followed by the NRF founded in 1909 by
      Gide, Schlumberger and soon after with Gallimard. Mainly devoted to novels and
      plays, the NRF rapidly succeeded. During the war, Gheon acted in the health serv-
      ice. Then; he returned to the christianfaith, and lead his own way for creating
      numerous religious plays, honorated in Canada in 1938. In june 1944, he died in
      Paris.

PMID- 30204317
TI  - [Boris Vian and his failed meetings with cardiology].
AB  - Boris Wan, a mythical figure of the post war years, just missed the succession of
      therapeutic advances in cardiology in the mid of the XXth century. A acute
      articular rhumatism occurred in 1932, as penicillin, discovered in 1928, was not
      yet on the market. Aortic regurgitation followed. On July 20, 1955, a pulmonary
      edema occurs as the first case of open-heart surgery with extra corporeal
      circulation is performed by Charles Dubost in 1955. But only the aortic stenosis
      may benefit from this surgery. Regarding aortic regurgitation, an artificial
      valve is necessary. The first Starr-Edwards heart valve is implanted on August
      25, 1960. June 23 , 1959, Boris Wan made a sudden loss of consciousness probably
      due to a ventricular fibrillation. It is this same year that the electric shock
      is used for the first time, but only in hospital. Boris Wan died during transport
      to the Laennec hospital. Ambulances were not yet equipped with defibrillator.

PMID- 30204318
TI  - [Post traumatic stress during World War I and literature].
AB  - World War I was the archetype of an industrial conflict and its consequences have
      been million dead, some heavily disabling physical traumatisms beside serious
      neurological/psychological suffering. Some of the sequels had been noticed during
      previous wars such as Crimea War, Civil War, Franco-Prussian War, and were
      labeled as shellshock. In literature (Celine, Virginia Woolf, William, March,
      Gughenno and so on) some situations or characters evoked disorders, which have
      been described later as post-traumatic syndrome.

PMID- 30204319
TI  - [Pierre and Francois Mauriac, a privileged friendship between brothers].
AB  - Pierre and Francois have been the key figures of the Mauriac five children.
      Pierre introduced his hospital service in Bordeaux to bio-clinic and was a well
      known professor before he became the dean of the Faculty from 1936 to 1945. As
      hero during the Great War he remained loyal to the "victor of the battle of
      Verdun" while his brother Frangois became a fervent 'Gaullist', "each of them
      climbing the same mountain along another side" according to Francois Mauriac in
      1966. Pierre was a writer too and a medical adviser for the novelist.

PMID- 30204320
TI  - [Lung diseases and miscellaneous pathologies in the novels of Francois Mauriac
      and Pierre Benoit].
AB  - Two modern novelists of the 20th century native from the Landes, Francois Mauriac
      (1885-1970) and Pierre Benoit (1886-1962), were eager to locate a part of their
      novels in the French South-West. Beyond the silence and the torrid warmth of this
      "sand desert populated by pine trees", each of them make live, suffer and die
      their sick heroes from diseases treated with therapies of that time with the risk
      of voluntary or not drug misuse : tuberculosis, cardiac insufficiency, angina
      pectoris, puerperal and typhoid fevers and other diseases.

PMID- 30204321
TI  - [Cancer and literature].
AB  - A number of literary books relate the course of a cancer. These are testimonies
      on a personnal tumour or on the tumour of a proxy. They give a useful view of the
      disease by lay authors, complementary of the view of the physicians.

PMID- 30204323
TI  - [Not Available].

PMID- 30204324
TI  - Best practices for influenza testing Methodologies and implementation.

PMID- 30204325
TI  - Rapid point-of-care assays for influenza testing.

PMID- 30204326
TI  - Evaluation of diabetic marker Hba1c and anemia in the context of kidney disease.

PMID- 30204327
TI  - Screening for primary immunodeficiency diseases and follow-up testing.

PMID- 30204328
TI  - Screening newborn babies for SCID.

PMID- 30204329
TI  - Standardization and implementation of lab policies ensure hemostasis sample
      quality.

PMID- 30204330
TI  - Testing those most at risk for blood lead exposure.

PMID- 30204331
TI  - Pathogen discovery through deep sequencing.

PMID- 30204332
TI  - The autoimmune response and neuropsychiatric disorders.

PMID- 30204333
TI  - Outsourcing vs. insourcing Which strategy is the better way for labs to support
      their larger institution?

PMID- 30204334
TI  - PCR then and now Improvements to technologies expand clinical utilization.

PMID- 30204335
TI  - Taking issue with some OIG recommendations.

PMID- 30204336
TI  - Experimental therapy of graft-versus-host disease by mesenchymal stromal cells
      grown on oxide nanocoatings.
AB  - Immune aggression to transplanted allogeneic bone marrow, i.e. the graft-versus
      host disease (GVHD), could be decreased by the suppression of effector and/or
      activation of T- regulatory cells (Treg). This task could be solved by co
      transplantaiton of allogeneic bone marrow and mesenchymal stromal cells (MSCs).
      This study demonstrated the elevated immune modulating activity of MSCs by their
      culturing in vitro on Al203 oxide nanocoatings. Introduction of the cells to the
      animals with GVHD resulted in an increased content of Treg in the spleen of bone
      marrow recipients, reduced severity of the pathology, and higher survival of
      animals. Thefindings could be the basis for developing the new approaches to
      optimize the GVHD treatment methods involving the oxide nanocoating cultured
      MSCs.

PMID- 30204337
TI  - ANALYSIS OF QUANTAL PARAMETERS OF GABA RELEASE DURING SHORT-TERM DEPRESSION AND
      FACILITATION OF SYNAPTIC TRANSMISSION.
AB  - Changes in amplitudes of evoked inhibitory postsynaptic currents (eIPSCs) from
      rat cultured hippocampal neurons were studied using whole-cell patch-clamp
      technique in postsynaptic neuron and local extracellular electrical paired pulse
      stimulation of single presynaptic axon. Paired pulse depression (PPD) and paired
      pulse facilitation (PPF) were observed in studied 43 neurons. According to
      coefficient of variance (CV) analysis was found that CV of second respond was
      significantly larger than CV first by 57 % (n 26) during depression and
      significanty smaller by 27 % (n = 17) during facilitation. Thus, only presynaptic
      mechanism underlies short-term depression and facilitation. We also estimated
      quantal parameters assuming that transmitter release is reasonably described by a
      binomial distribution. We found that under our experimental conditions there were
      no significant changes in GABA release probability during PPD and PPF. The values
      of mean quantal content and mean number of sites of transmitter release were the
      same for first stimulus in pair and were equal 9.7 in depression and 5 in
      facilitation of synaptic transmission. The values both of them for second
      stimulus were significant decreased by 28 and 26% during PPD and were significant
      increased by 14 and 11% during PPF, respectively. Thus, there is significant
      difference in quantal parameters characterizing GABA release during short-term
      depression and facilitation of synaptic transmission.

PMID- 30204338
TI  - AMINOACID RESIDUES INVOLVED IN POSITIVE MODULATION OF alphal GLYCINE RECEPTORS BY
      GINKGOLIC ACID.
AB  - Previously, we have shown that ginkgolic acid has an ability to potentiate
      currents, mediated by alphal subunits of glycine receptor. In order to define the
      mechanism of subunit specific action of ginkgolic acid we have performed
      comparative analysis of the amino acid sequences of at and alpha2 subunits of
      glycine receptor. Amino acids that contribute to the different action of
      ginkgolic acid on glycine receptors formed by these subunits were determined.
      Using whole-cell configuration of patch-clamp recording, we have demonstrated
      that mutation of three residues in alpha2 subunit for corresponding ones from
      alphal subunit makes alpha2 receptors sensitive to the potentiation by ginkgolic
      acid. Currents, mediated by alpha2 mutant receptors, increased by 89+/-14% after
      application of ginkgolic acid. Similarly to ai receptors alpha2 mutant receptors
      have shown a decrease in EC50. for glycine under the action of ginkgolic acid.
      Thus, subunit selectivity of the ginkgolic acid is in strong connection with
      three amino acid residues that are different in alpha1 And alpha2 subunits of
      glycine receptor.

PMID- 30204339
TI  - CALIX[4]ARENES AS MODULATORS OF ENERGY-DEPENDENT CA2+_ACCUMULATION AND
      FUNCTIONING OF THE ELECTRON TRANSPORT CHAIN IN SMOOTH MUSCLE MITOCHONDRIA.
AB  - The influence of supramolecular macrocyclic compounds calix[4]arenes (C-97, C-99,
      C-107) at a concentration of 100 nM in the process of energy-dependent Ca2+
      transport in isolated mitochondria of smooth muscle, as well as autofluorescence
      mitochondrial coenzyme NADH, FAD and hydrodynamic diameter of these organelles
      was investigated. Using Ca2+-sensitive fluorescent dye Fluo-4 AM it was shown
      that the selected calix[4]arenes can suppress energy-dependent accumulation of
      Ca2+ by mitochondria. Accumulation of Ca2+ (80 jiM in the medium) accompanied by
      the growth of the fluorescent probe response from a conventional unit to a value
      of 1,57+/-0,04 (n=5). Calix[4]arenes C-97, C-99, C-107 falls fluorescent signal
      below the 0,88+/-0,08, 0,92+/-0,08 and 0,78+/-0,04 respectively. Thus, the
      selected calix[4]arenas lead to release of previously accumulated Ca2+ from
      mitochondria. Under the influence of C-97 and C-99 fluorescent signal from NADH
      reduced to -0,11+/-0,02 and -0,12+/-0,02, respectively, in relation to the
      reference value - -0,05+/-0,01 (n=5). Analysis of fluorescence response NADH and
      FAD in a suspension of isolated mitochondria suggests that the effects of test
      compounds on the functional activity of the electron transport chain is
      associated with the initial stimulation of its 1-th complex and subsequent
      inhibition of Ca2+-dependent NAD- containing Krebs cycle dehydrogenases. Along
      with this, the use of photon correlation spectroscopy to assess changes in the
      volume of mitochondria (their hydrodynamic diameter) under the action of selected
      calix[4]arenes has shown that interference with the electron transport chain
      leads to changes in the osmotic balance between the matrix of the mitochondria
      and the external environment. The result is the growth of isolated organelles
      volume. In particular, the hydrodynamic diameter of mitochondria increased by
      22+/-6 % and 34+/-8 % (n=5) in presence of C-97 or C-99. The conclusion was done
      about the advisability of further studies of the calyx[4]arenes effect on smooth
      muscle Ca2+-homeostase and mitochondrial bioenergetics in order to find effective
      modifiers of their func- tional activity.

PMID- 30204340
TI  - Role of matrix metalloproteinase 9 and its tissue inhibitor 1 in development and
      prognosis of diabetic retinopathy.
AB  - The article presents the results of investigation of violations in the
      proteolysis system in patients with type 2 diabetes and diabetic retinopathy
      (DR). We studied the levels of matrix metalloproteinase-9 (MMP-9) and tissue
      inhibitor of matrix metalloproteinase-I (TIMP-1) in the blood and in the
      intraocularfluid ofpatients with type 2 diabetes depending upon the stage of DR.
      We have established that the level of MMP-9 and TIMP- in the blood and in the
      intraocular fluid increased in patients with type 2 diabetes without signs of DR
      and with any stage of DR compared to the levels of these parameters in patients
      without diabetes. Increasing the levels of MMP-9 and TIMP-J took place with
      increasing of DR severity and reached its maximum levels at the proliferative
      stage of DR. It was found that the levels of MMP-9 in the intraocular fluid and
      type 2 diabetes duration affected theprobability of developing diabetic macular
      edema. At the level of MMP-9 105 ng/ml and 2 diabetes duration 10 years, the
      probability of developing macular edema was 100%. As a result of the construction
      ofpredictive models it was found that the level of MMP-9 in the intraocular
      fluid, stage of DR at the beginning of observation and type 2 diabetes duration
      had influence on the probability of the development ofproliferative DR over 4
      years offollow-up. If the level of MMP-9 100 ng/ml, type 2 diabetes duration 10
      years and absence of DR at the beginning of observation were observed the
      probability of developing proliferative DR would compose 85.9%.

PMID- 30204341
TI  - SPECIFIC FEATURES OF CHRONORHYTH- MOLOGIC CHANGES OF THE ION-REGU- LATING
      FUNCTION OF THE KIDNEYS UN- DER THE HYPOFUNCTION OF THE PINEAL GLAND.
AB  - The paper investigates the specific features of chronorhythmologic changes of the
      ion-regulating function of the kidneys under the hypofunction of the pineal
      gland. For the study of hypofunction of the pineal gland, animals were maintained
      under constant light stimulation during 7 days. It has been established that the
      hypofunction epiphysis point out disturbances of the phasic structure of the ion
      regulating function in relation to chronograms of the intact group of rats. In
      terms of physiological pinealectomy observed in- crease in the excretion of
      sodium ions (6,11+/-0,81 mmol/h) and the concentration of this cation in the
      blood plasma remained elevated around the clock. The obtained results indicate
      significant changes of integral characteristics of the rhythms of electrolyte
      metabolism and the important role of the pineal gland in ensuring physiological
      homeostasis.

PMID- 30204342
TI  - Flavonoid quercetin reduces gliosis after repetitive mild traumatic brain injury
      in mice.
AB  - The effect of water-soluble form of quercetin on the structural changes of glial
      cells in hippocampus was investigated in mice after repetitive mild traumatic
      brain injury. Reactive astro- and microgliosis in hippocampus were observed after
      brain injury. Iba 1 and GFAP immunohistochemistry was used to visualize
      astrocytes and microglia cells. Immunopositive cells were counted in hippocampal
      CA 1-area at 5th, 10th and 30th days since thefirst injury and at 5th, 10th and
      30th days since thefirst quercetin injection. Administration of quercetin leaded
      to the decrease in number of activated glial cells. Thus, our study demonstrates
      thefollowing: repetitive mild traumatic brain injury in mice is associated with
      reactive gliosis; quercetin showed neuroprotective effects by reducing this
      gliosis. In view of the described, use of quercetin is appropriate for
      pharmacological correction of cerebrovascular disorders after traumatic brain
      injury.

PMID- 30204343
TI  - EFFECT OF HYDROGEN SULPHIDE DONOR ON INTRAOCULAR PRESSURE IN RATS.
AB  - It has been investigated the effect of a 1% solution of sodium hydrosulfide NaHS
      on intraocular pressure (IOP) in intact rats and during modeling them of ocular
      hypertension, using prolonged systemic administration of adrenaline. A single
      administration of hydrogen sulphide donor as drops into cavity of the eye has
      caused the hypotensive effect, which was pretty weak in the normotensive eyes and
      pronounced in the eyes with ocular hypertension. Long-term administration ofNaHS
      solution by the scheme, during administration of adrenaline as a model inductor,
      has largely prevented IOP rise. It done conclusion that hydrogen sulphide is
      involved in the regulation of eye hydrodynamics and maintaining normal levels of
      IOP.

PMID- 30204344
TI  - COMPARISON OF SPECTROSCOPIC PROPERTIES OF INTRAOCULAR FLUID IN PATIENTS WITH
      CATARACT AND PRIMARY OPEN-ANGLE GLAUCOMA.
AB  - This paper presents a comparison ofspectroscopic properties of aqueous humour in
      patients with cataract (60 patients, 60 eyes) and combination of cataract and
      primary open angle glaucoma (POAG, 36 patients, 36 eyes). The samples of aqueous
      humour were collected during the surgery. Both groups of patients were treated
      with different types of local drug antihypertensive therapy with different
      multiplicity and duration of instillation during the preoperative period. The
      absorption spectrum of aqueous humour were measured in the wavelength range 190
      1100 nm. There were two absorption bands with maximums at 202 and 267 nm in the
      absorption spectrum (2nd maximum of some samples was shifted to larger
      wavelengths). The mean absorbance of aqueous humour at 202 nm in patients without
      POAG was significantly lower than in patients with POAG. This difference could be
      explained with accumulation of metabolites in aqueous humour of patients with
      POAG, which in turn may be caused by deceleration of aqueous humour flow in
      patients with POAG. Meanwhile, there were no statistically significant
      differences of mean absorbance of aqueous humour at 267 nm between the patients
      of both groups.

PMID- 30204345
TI  - STATUS OF GLUTATHIONE-DEPENDENT LINK OF BLOOD ANTIOXIDANT SYSTEM UNDER
      APPLICATION OF FENUGREEK SEED POWDER IN ANIMALS WITH EXPERIMENTAL OBESITY.
AB  - The content of reduced glutathione (GSH) and activity of glutathione-dependent
      enzymes: glutathione peroxidase (GP) and glutathione-S-transferase (GT) in blood
      serum of rats in the diet supplemented of fine powder seeds Trigonella foenum
      graecum L. on the background of experimental obesity. It was established that the
      development of obesity in rats was accompanied by violation of homeostasis in the
      glutathione-dependent system of blood serum. It has been shown that animals on
      high-calorie diet-along 14 weeks had a decrease (1,2) in GSH concentration, a
      decline (1,7) in GP activity and the increase (1,7) of GT activity compared with
      control values. Addition to high-calorie diet 2% fine powder seeds Trigonella
      foenum graccum L. reduced the body weight gain by 21%, carried positive
      modulating effect on the content of GSH and GP, GT activity in animals with
      experimental obesity.

PMID- 30204346
TI  - THE EFFECT OF GADOLINIUM ORTHOVANADATE NANOPARTICLES BY NEONATAL INDUCED
      REPRODUCTIVE DISEASE IN MALE RATS.
AB  - For the purpose to develop of method for treatment of male hypofertility the
      efficiency of gadolinium orthovanadate nanoparticles (NP GdVO4) in rats with
      neonatal induced reproductive disease, has been investigated. The progeny of
      intact rats parents were exposed to emotional stress (Maternal separation
      stressn) and received an excessive amount of the blend of phytoestrogens (Ph)
      with mother's milk (1st group) from 3 to 22 day life. At the age of 10 months
      males received NP GdVO4 (0.33 mg/kg; 2nd group) or speman (158 mg/kg; 3rd group)
      with feed over the 70 days. Sexual behavior and fertility of males were
      investigated; the integrated indicator of reproductive potential (FI) was
      calculate and was estimated with the data of animals from group Control who were
      given vehicle (water). In the 1st group sexual behavior of males was
      characterized by accelerating sexual responses on female (double shortening of
      mounting and intromission latency) and a reduced ability to achieve ejaculation
      and to start the second round of copulations. The less females have been
      inseminated by these males (67% vs. 91% in Control group), but almost all became
      pregnant. As a result of the neonatal induction deterioration in the quality of
      male gametes intrauterine pregnancy loss increased more than twice, and the total
      number of foetus decreased (on 21%). These changes have led to a reduction of the
      male integrated indicator of reproductive potential (Fi) in 2.6 times compared
      with control animals. Using a NP GdVO4 rehabilitated male sexual behaviour
      indicators to Control group level, resulting in an increase in the number of
      fertilized females (up to 95%). In pregnant females decreased fetal losses (up to
      15.2% vs. 18.1% in control, p<0,05) and increase in the number of fetuses (on
      25%, p<0,05) that shows an improvement in the quality of sperm. The integrated
      indicator of reproductive potential (F1) increased to (8.3 +/- 0.5) vs. (3.0 +/-
      0.3) u. in the 1st group (without treatment), that statistically higher than in
      groups Control and 3rd. Application of NP GdVO4 in rats with neonatal inductive
      pathology of the reproductive function and metabolic disorders normalizes sexual
      behaviour, the quality of sperm that restores male fertility and improves
      reproductive potential much more efficiently than the reference drug speman.

PMID- 30204347
TI  - THE PECULIARITIES OF ARGINASE PATHWAY OF L-ARGININE IN SPERMATOZOA IN MEN WITH
      DIFFERENT FORMS OF PATHOSPERMIA.
AB  - The changes in arginase activity of spermatozoa and hormonal profile of
      peripheral blood of infertile men with various forms pathospermia have been
      studied. It has been found that arginase activity in the sperm cells of men with
      oligozoo-, antenozoo-, oligoastenozoo- and leucocytospermia is decreased in 2.1,
      2.3, 2.4 and 3.3 times respectively. This indicates about inhibition of arginase
      pathway of L-arginine metabolism, which is not significantly dependent on the
      type of disruption of spermatogenesis. The most significant changes have been
      observed in infertile men with leucocytospermia since white blood cells stimulate
      the formation of reactive oxygen species, induction and development of oxidative
      and nitrative stress in spermatozoa. Inhibition of arginase pathway of L-arginine
      metabolism has adaptive role, which is to limit bioavailabil- ity of L-arginine
      and to prevent excessive formation of NO in cytotoxic concentrations to sperm
      cells. It has been noted changes in serum concentrations of gonadotropin and sex
      hormones in men with various forms of pathospermia. The most expressed
      significant changes were in levels of follicle stimulating hormone and
      testosterone. The concentration of follicle stimulating hormone in patients with
      oligozoospermia caused by hypogonadism is twice higher and in patients with
      leucocytospermia in 1.8 times higher than in fertile men. In patients with
      astenozoospermia this value is in 2.2 times lower than in normozoospermic samples
      but within the physiological norm. The testosterone level in men with
      oligozoospermia is in 1.6 times lower than in fertile men but within the
      physiological norm. It has been found that arginase inhibition of spermatozoa
      po6itively correlated with a decrease in their concentration in the ejaculate of
      infertile men with oligozoospermia (r =0.68).

PMID- 30204348
TI  - The Distribution of Dental Health Specialist Locations in Sri Lanka.
AB  - AIM: To investigate the distribution of dental health specialist locations
      staffed by Oral and Maxillo-Facial Surgeons (OMF), Restorative dentists, and
      Orthodontists in Sri Lanka in relation to population distribution and socio
      economic status. METHODS: Specialist dental locations were mapped using GIS
      (Geographic Information System) and overlayed with census population data and
      socio-economic quintiles. RESULTS: Overall, there was an uneven geographic
      distribution of the total 55 specialist dental locations and 74 attributed
      specialist work force within the country. Access to specialist care is remarkably
      high in Western and Central provinces, compared to the Northern, Eastern and
      North Central provinces. When the geographic distribution was compared to
      population socio-economics, it was found that in Sri Lanka only 22.3%, 44.4%, and
      25.4% of the most disadvantaged lived within 20 kms from an Orthodontic, OMF and
      Restorative clinic respectively, compared to 66.3%, 82.8% and 44.7% of the least
      disadvantaged. CONCLUSION: The findings of this study can contribute to the
      decision-making process when determining future locations of dental specialist
      clinics and identifying subgroups in the population who are geographically and
      socio-economically isolated from accessing care.

PMID- 30204349
TI  - ?

PMID- 30204350
TI  - ?

PMID- 30204351
TI  - ?

PMID- 30204352
TI  - ?

PMID- 30204353
TI  - ?

PMID- 30204354
TI  - ?

PMID- 30204355
TI  - ?

PMID- 30204356
TI  - ?

PMID- 30204357
TI  - ?

PMID- 30204358
TI  - [The Flavonoids of Chemical Constituents of Osmanthus fragrans Roots].
AB  - Objective: To investigate the constituents of the roots in Osmanthus fragrans.
      Methods: The Osmanthus fragrans roots alcohol extract solution were separated and
      purified by silica gel,Sephadex LH-20 and other materials, the structures were
      identified by physicochemical properties and spectral analysis. Results: Thirteen
      flavonoids were isolated from the roots of Osmanthus fragrans,which identified as
      glabrol ( 1), dihydroquercetin( 2),2'-hydroxy-5,7,8-trimethoxyflavone(
      3),lupinifolin( 4), phloretin( 5), apigenin ( 6), calycosine( 7), quercetin(
      8),3',4',5,7-tetrahydroxy flavanone( 9),5-hydroxy-7,8,2',6'-tetramethoxyflavone(
      10),isoliquiritigenin( 11),tonkinensisol( 12),kaempferol ( 13). Conclusion:
      Compounds 1 ~ 5,7,9 ~ 12 are isolated from the Osmanthus fragrans for the first
      time.

PMID- 30204359
TI  - [Chemical Constituents from Stauntonia chinensis].
AB  - Objective: To study the chemical constituents of Stauntonia chinensis. Methods:
      The chemical constituents were isolated and purified by column chromatography on
      silica gel,ODS,Sephadex LH-20 and MPLC. Their structures were elucidated on the
      basis of physicochemical properties and special analysis. Results: Seven
      compounds were isolated from the leaves of Stauntonia chinensis,whose structures
      were elucidated as 3-O-beta-D-glucopyranosyl-( 1 ->3)-[beta-D-xylopyranosyl-( 1 
      >2) ]-alpha-L-arabinopyranosyl-28-O-[alpha-L-rhamnopyranosyl-( 1 ->4)-beta-D
      glucopyranosyl-( 1 ->6)-beta-D-glucopyranosyl]-3beta-hydroxy-30-norolean-12,20(
      29)-dien-28-oic acid( 1),3-[( O-beta-D-glucopyranosyl-( 1->3)-[alpha-L
      rhamnopyranosyl-( 1 ->2) ]-alpha-L-arabinopyranosyl) oxy]-30-norolean-12,20( 29)
      dien-28-oic acid O-beta-D-glucopyranosyl-( 1 -> 6)-beta-D-glucopyranosyl ester(
      2),3-O-beta-D-[( alpha-L-xylopyranosyl-( 1 -> 2)-O-alpha-L-arabinopyranosyl)oxy]
      30-norolean-12-en-28-oic acid alpha-L-rhamnopyranosyl-( 1 -> 4)-O-beta-D
      glucopyranosyl-( 1 -> 6)-O-beta-D-glucopyranosyl ester( 3), yemuoside YM27( 4),
      yemuoside YM21( 5),yemuoside YM10( 6) and yemuoside YM7( 7). Conclusion:
      Compounds 1 ~ 3 are isolated from this plant for the first time.

PMID- 30204360
TI  - [Chemical Constituents from Fruiting Bodies of the Basidiomycete Postia
      balsamea].
AB  - Objective: To study the chemical constituents from fruiting bodies of Postia
      balsamea. Methods: The fruiting bodies of Postia balsamea was extracted,the
      compounds were isolated by silica gel column chromatography. The structures were
      elucidated by the spectral analysis. Results: Seven compounds were isolated and
      identified as botulin ( 1),( 22 E,24R)-5alpha,8alpha-epidioxy-ergosta-6,22-dien
      3beta-ol( 2),( 22 E,24R)-5alpha,8alpha-epidioxy-ergosta-6,9( 11),22-trien-3beta
      ol( 3),( 22 E,24R)-ergosta-7,22-dien-3beta-ol( 4), betulinic acid( 5),( 22 E,24R)
      ergosta-5,7,22-trien-3beta-ol ( 6) and stearic acid( 7). Conclusion: All the
      compounds are isolated from this species for the first time.

PMID- 30204361
TI  - [Simultaneous Determination of Protocatechuic Acid,Kaempferol Biotin Glucoside
      and Quercitrin in Rat Plasma and Pharmacokinetics By UPLC-MS/MS].
AB  - Objective: To develop a sensitive and reliable ultra performance liquid
      chromatography tandem mass spectrometry ( UPLC-MS / MS) method for simultaneous
      determination and pharmacokinetics of protocatechuic acid, kaempferol biotin
      glucoside and quercitrin in rat plasma, and study their pharmacokinetic
      characteristics in rats. Methods: Three compounds were simultaneously determined
      by UPLC-MS / MS on Waters BEH C18( 50 mm * 2. 1 mm,1. 7 MUm) column. The mobile
      phase was 0. 1% acetonitrile formic acid and0. 1% aqueous formic acid, and
      programmed in a linear gradient mode. The compounds were ionized in the
      electrospray ionization ion source of the mass spectrometer and detected in MRM
      mode. Results: The t1 /2of protocatechuic acid,kaempferol biotin glucoside and
      quercitrin after intravenous injection were( 41. 9 +/- 12. 3),( 71. 3 +/- 56. 8)
      and( 90. 3 +/- 74. 8) min. The Cmaxwere( 1. 7 +/- 0. 7) MUg / m L,( 2. 1 +/- 0.
      9) MUg/m L,( 8. 7 +/- 3. 7) MUg/m L. Conclusion: The established method is
      specific,rapid,accurate and sensitive,and is proved to meet the requirements of
      biological sample analyses,and is suitable for the concentration determination of
      protocatechuic acid, kaempferol biotin glucoside and quercitrin in rat plasma,
      three compounds are all best fitted to the two-compartment open pharmacokinetic
      model.

PMID- 30204362
TI  - [The Effect in Extraction of Different Ratio of Dahuang-Taoren for Ten Kinds of
      Chemical Constituents from Rhizoma Rhei].
AB  - Objective: To investigate the effect of Dahuang-Taoren with different proportion
      of extraction amount changes of ten kinds of chemical constituents in Rhizoma
      Rhei. Methods: Uniform method to set different ratio( 1? 5,2? 5,2? 3,1? 1,3? 2,5?
      2,5? 1),and set the control group ( Dahuang-Taoren( 1 ? 0). HPLC was used to
      determine the content of ten constituents as gallic acid,( +)-catechin,sennoside
      B,anthraquinones( aloe-emodin,rhein,emodin,chrysophanol,physcion,chrysophanol-1-O
      glucoside,emodin major grape glycoside) in different ratio of drug. Different
      proportions of Dahuang-Taoren on the extraction amount of ten chemical components
      in Rhizoma Rhei changes were analyzed. . Results: Compared to the control group,
      Dahuang-Taoren with different ratio( 5? 1,5? 2,3? 2) in a sample with increasing
      proportion of Taoren,the extraction amount of ten kinds of constituents of
      Rhizoma Rhei gradually decreased;Dahuang-Taoren with ratio of 1? 1,ten kinds of
      constituents in extraction of total amount arrived minimum value. Dahuang-Taoren
      with different ratio( 2? 3,2? 5,1? 5) in a sample with increasing proportion of
      Taoren,the extraction amount of gallic acid,( +) catechin,chrysophanol of Rhizoma
      Rhei increased significantly. Conclusion: There is obvious change in chemical
      constituents of the extraction amount of Rhizoma Rhei with the change of the
      ratio in Dahuang-Taoren, and Dahuang-Taoren with the ratio( 2? 3,2? 5,1? 5),the
      extraction amount of gallic acid,( +)-catechin,sennoside B,aloe
      emodin,emodin,chrysophanol,physcion,chrysophanol-1-O-glucoside are significantly
      higher than control group.

PMID- 30204363
TI  - [Preparation of Salviae Miltiorrhiza and Ligustrazine Hydrochloride Nasal
      Thermosensitive in Situ Gel and Study on Characterization of Its Nasal Mucosal
      Permeability].
AB  - Objective: To prepare the salviae miltiorrhiza and ligustrazine hydrochloride
      nasal thermosensitive in situ gel and to study the characterization of its nasal
      mucosal permeability. Methods: With gelling temperature as the dependent
      variable, the contents of poloxamer 407( P407), poloxamer 188( P188) and PEG-6000
      as independent variables. The best prescription was optimized by central
      composite design-response surface methodology. The release in vitro and the skin
      permeation ability were evaluated in Franz diffusion cell. Results: The optimal
      formulation composed with the dosage of P407,P188 and PEG-6000 were 18%,7% and
      1%,respectively. The cumulative release in vitro was over 70% after 12 h, and the
      release curve conformed to the first-order kinetic equation. The cumulative
      permeation of salviae miltiorrhiza and ligustrazine hydrochloride in the gel were
      2 649. 77 MUg / cm2 and 119. 72 MUg / cm2 after 12h. Conclusion: The central
      composite design-response surface methodolog was stable and feasible for
      preparation of nasal thermosensitive in situ gel of salviae miltiorrhiza and
      ligustrazine hydrochloride, the drug-loaded gel has sustained release effect.

PMID- 30204364
TI  - [Experiment on Jianpi Qingre Huoxue Decoction Drug Serum Regulates SW480 Cell
      Proliferation,Apoptosis,Cycle and the Expression of beta-Catenin by Altering
      PI3K/Akt Signal Pathway].
AB  - Objective: To study Jianpi Qingre Huoxue decoction( JPQRHX) in preventing colon
      cancer by observing SW480 cells proliferation,apoptosis,cycle and the expression
      of P-beta-catenin, and to research its mechanism. Methods: SW480 cells were
      incubated with serum containing blank serum, different concentrations of JPQRHX
      decocition and PI3 K blocking agent LY294002 for 24 h,respectively. Cell
      proliferation was detected by MTT assay, cell cycle and apoptosis were detected
      by flow cytometry. The protein translocation of P-beta-catenin was assayed by
      immunofluorescent staining. Results: The inhibitory rate and apoptosis rate in
      JPQRHX decoction group were higher than control group( P < 0. 05),respectively. S
      phase cells were increased significantly, and G1 phase cells and LY294002 group
      cells were decreased significantly( P < 0. 05). The P-beta-catenin in JPQRHX
      decoction groups were mainly expressed in membrane, while the P-beta-catenin in
      the control group was characterized by deletion in membrane and increased in
      nucleus. Conclusion: JPQRHX decoction has the ability in curing colon cancer, and
      the mechanism is associated with altering the expression of P-beta-catenin in the
      cells nucleus, blocking SW480 cells cycle at G1 phase, inhibiting SW480 cells
      proliferation, and inducing SW480 cell apoptosis.

PMID- 30204365
TI  - [Study of Berberine on Attenuating PM2.5-Induced Vascular Endothelial Cells
      Injury by ERK1/2 Signal Pathway].
AB  - Objective: To investigate the effect and mechanism of berberine in attenuating
      PM2. 5-induced human umbilical vein endothelial cells EA. hy926 injury. Methods:
      The samples of fine particulate matter( PM2. 5) were collected and made into
      suspension. Different concentrations of PM2. 5( 0,20,200,400 mg / L) were added
      into EA. hy926 cells for 24 h. The viability of EA. hy926 cells was detected by
      MTT assay, and apoptosis of EA. hy926 cells was detected by flow cytometry, the
      expressions of p-ERK1 /2,BAX and BCL-2 in the EA. hy926 cells were measured by
      Western blot,the contents of IL-6,TNF-alpha were measured by ELISA, the content
      of MDA, and the activities of SOD and LDH in the EA. hy926 cells culture
      supernatant were measured, respectively. Different concentrations of berberine(
      10,50,100 MUmol / L) and PD98059( 20 MUmol / L) was added into the EA. hy926
      cells to observe the effect of berberine. Results: Compared with control
      group,PM2. 5 decreased the viability in a dose dependent manner, and
      significantly upgraded the protein levels of p-ERK1 /2 and BAX / BCL-2 ratio,PM2.
      5 increased the apoptosis of EA. hy926 cells, and increased the contents of IL
      6,TNF-alpha and MDA, increased the activity of LDH, and decreased SOD activity in
      the EA. hy926 cells( P < 0. 05). Compared with PM2. 5 group, berberine increased
      the viability of EA. hy926 cells in a dose dependent manner,PM2. 5 significantly
      downgraded the protein levels of p-ERK1 /2 and BAX / BCL-2 ratio, and decreased
      the apoptosis of EA. hy926 cells, decreased the contents of IL-6,TNF-alpha and
      MDA, and decreased the activity of LDH, and increased SOD activity in the EA.
      hy926 cells( P < 0. 05). Conclusion: Berberine attenuates PM2. 5-induced EA.
      hy926 cells injury by inhibiting ERK1 /2 pathway.

PMID- 30204366
TI  - [Network Pharmacological Studies of Puerariae Radix in Improving Insulin
      Resistance].
AB  - Objective: To investigate the active components and potential mechanism of
      Puerariae Radix in improving insulin resistance by using network pharmacological
      method. Methods: Key target proteins related with insulin resistance were
      selected based on molecular docking technology, and then took the selected
      components with 31 target proteins of four pathways for docking. Meanwhile,
      component-target proteins network was established to network analysis by software
      Cytoscape 3. 2. 1. Results: 19 compounds had close interactions with four
      pathways such as AMPK. There were 13 compositions can verify through literature,
      which revealing that active ingredients and potential molecular mechanism of
      Puerariae Radix in improving insulin resistance, preliminarily. Conclusion: The
      network pharmacological method is helpful to explore the possible active
      components in Puerariae Radix and elucidate the mechanism.

PMID- 30204367
TI  - [Sesamin Preconditioning Attenuates Myocardial Ischemia Reperfusion Injury in
      Rats Through Activation of Akt/eNOS Signaling Pathway].
AB  - Objective: To investigate the protective effect of sesamin on myocardial ischemia
      reperfusion injury in rats, and to study the possible mechanism. Methods: 50 SD
      rats were randomly divided into control group, sham operated group, model group,
      high-dose sesamin group( 160 mg / kg) and low-dose sesamin group( 80 mg /
      kg),with 10 rats in each group. Rats in sesamin groups were administered
      intragastrically with sesamin for 7 d. Then all rats except those in sham
      operated group were subjected to myocardial ischemia-myocardial ischemia
      reperfusion injury model by coronary artery ligation for 40 min and subsequent
      reperfusion for 120 min. Serum cardiac troponin I( c TnI) and lactate
      dehydrogenase( LDH),levels of total antioxidant capacity( TAOC) and nitric oxide(
      NO) in serum and myocardial tissues,Caspase-3 activity in myocardial tissues were
      detected by colorimetric assay. Cardiomyocyte apoptosis was evaluated by TUNEL
      assay. Phosphorylation level of endothelial nitric oxide synthase( eNOS) and
      Protein kinase B( Akt), protein expression of superoxide dismutase( SOD) in
      cardiac tissue were determined by Western blot. Results: Pretreatment with
      sesamin significantly ameliorated myocardial injury in rats which induced
      myocardial ischemia and reperfusion injury by reduced levels of serum c TnIand
      LDH( P <0. 05 or P < 0. 01). Supplementation with sesamin resulted in a
      significant increasing of total antioxidant capacity and NO level in serum and
      myocardial tissues and cardiomyocyte apoptosis( P < 0. 05 or P < 0. 01),and
      remarkable decrease the Caspase-3 activity in myocardial tissues and
      cardiomyocyte apoptosis( P < 0. 05 or P < 0. 01). Sesamin significantly up
      regulated the protein expression of SOD in cardiac tissues, and the levels of
      phosphorylated eNOS and Akt increased notably( P < 0. 05 or P < 0. 01).
      Conclusion: Pretreatment with sesamin effectively ameliorated myocardial ischemia
      reperfusion injury in rats, and the mechanism might be related to enhancing its
      antioxidant capacity and the activation of Akt / eNOS signaling pathway and
      subsequent increase of NO synthesis and suppression of cardiac myocyte apoptosis.

PMID- 30204368
TI  - [Research on the Anti-Pulmonary Fibrosis Effect of the Bletilla striata
      Polysaccharide in Rat Silicosis Model].
AB  - Objective: To investigate the anti-pulmonary fibrosis effect and the possible
      molecular mechanism of the Bletilla striata polysaccharide. Methods:
      Polysaccharide was prepared by water reflux extraction plus ethanol precipitation
      method, and following deproteinization process by Sevage method. Rat silicosis
      model was established by invasive intratracheal instillation method. The effect
      and molecular mechanism of the polysaccharide was evaluated by lung indexes, lung
      pathological change, serum levels of SOD,MDA,NF-kappaB,IL-1beta,PDGF,TGF
      beta1,TNF-alpha,HYP were detected, and the contents of CD3~+,CD4~+,CD8~+T lymph
      cells and CD4~+/ CD8~+ratio were detected by flow cytometry. Results: Both low(
      100 mg / kg) and high( 400 mg / kg) dosage polysaccharide treatment could
      remarkably elevate the serum SOD level and reduce the MDA,NO level, and
      effectively reverse the CD4~+/ CD8~+ratio comparing with the model group( P < 0.
      01). Except the TNF-alpha level was significantly lower in the high dosage
      treatment group, there was no other effect in inflammatory cytokines and HYP
      content in serum. HE pathological section confirmed that the Bletilla striata
      polysaccharide treatment group can not effectively prevent lung fibrosis.
      Conclusion: The Bletilla striata polysaccharide has remarkable regulation effect
      on antioxidation system and immune system, but can not effectively prevent lung
      fibrosis, more effort should be made to study the active antipulmonary fibrosis
      components of Bletilla striata.

PMID- 30204370
TI  - [Comparison of Laccase Activity of Different Strains of Ganoderma spp.].
AB  - Objective: To explore the relationship between the laccase activity and growth of
      Ganoderma spp.,to screen the highproducing laccase strains. Methods: The mycelium
      was cultured in PDA solid medium,and the laccase activity was measured by
      ABTS+method. The content of polysaccharide was determined by phenol sulfuric acid
      method. Results: Ganoderma gibbosum grew more rapidly in the early stage,and the
      laccase activity reached maximum( 1 476. 64 U/g) in the 4th day,which was 11. 37
      times larger than that of sweet Ganoderma lucidum. Ganoderma gibbosum had the
      significant advantage after a comprehensive analysis. The polysaccharide content
      of Ganoderma lucidum of Shinshu was lower; the growth rate of Ganoderma lucidum
      strain S3 was stable, and the content of polysaccharide was medium. Conclusion:
      There are some differences in the growth rate of Ganoderma spp., and there is a
      certain correlation between the laccase activity and growth. Ganoderma gibbosum
      is the highest-producing laccase strain among the screening strains.

PMID- 30204369
TI  - [Study on Total Triterpenoids Content of Enrichment Mineral Elements of Inonotus
      Obliquus].
AB  - Objective: To study the influence of different mineral elements enrichment of
      calcium, iron, and zinc on the growth of the mycelium from Inonotus obliquus, to
      explore the influence on total triterpenoids content of Inonotus obliquus.
      Methods: Mineral elements were enriched on Inonotus obliquus, total triterpenoids
      extraction methods and determination methods were optimized, and total
      triterpenoids content of Inonotus obliquus were compared through different
      mineral elements enrichment. Results: The mycelial growth and yield were promoted
      obviously when 1 000 mg/L Ca(NO3)2 was added in the culture medium, and the
      calcium enrichment rate could reach to 0.07%. The most appropriate iron source
      was Fe2(SO4)3, and the iron enrichment rate could reach to 0.29% when 300 mg/L
      Fe2(SO4)3 was added. 175 mg/L Zn SO4 led to the strongest mycelium growth vigor,
      and the zinc enrichment rate could reach to 0.57%. The total triterpenoids
      content of Inonotus obliquus was the highest (0.058 mg/mL) as enrichment of
      calcium element, the total triterpenoids content of Inonotus obliquus was the
      least (0.04 mg/mL) as enrichment of iron elements. Conclusion: The total
      triterpenoids content of Inonotus obliquus was the highest when calcium element
      was enriched. This study provides a new method and basic data for the factory
      production of Inonotus obliquus.

PMID- 30204371
TI  - [AFLP and HPLC Fingerprints Analysis of Codonopsis Species from Original Areas
      and the Same Planting Base].
AB  - Objective: To investigate the influence of environment on the genetic structure
      and chemical ingredients of different Codonopsis species. Methods: Amplified
      fragment length polymorphism( AFLP) molecular markers were used to analyze the
      genetic polymorphism of Codonopsis species from 24 different populations,and high
      performance liquid chromatography( HPLC) fingerprints were performed to analyze
      the chemical ingredients of 10 batches of Codonopsis roots. Results: According to
      species classification,the 24 populations were categorized into three groups by
      UPGMA cluster method. The samples of Codonopsis pilosula var. modesta introduced
      from Wenxian( Gansu Province) and Jiuzhaigou County( Sichuan Province) were
      clustered into Group I. The Codonopsis tangshen population introduced from
      Banqiao( Hubei Province) was clustered into Group II. The populations from
      Codonopsis pilosula introduced to Shanxi Province GAP base,and the wild and
      cultured populations of Codonopsis pilosula collected from Shanxi Province were
      into Group III. The similarity of HPLC fingerprints among three Codonopsis
      species introduced into the same environment was over 0. 8. Conclusion: Genetic
      differences of three Codonopsis species from original areas and Codonopsis
      species introduced into Shanxi Province were caused by their inter-species
      genetic characteristic. Meanwhile, the similarities of genetic backgrounds in
      Codonopsis species were related to geographic space, and chemical ingredients of
      Codonopsis were easily influenced by the cultivation environment.

PMID- 30204372
TI  - [Correlation Between Index Components and Climatic Factors of Pseudostellariae
      Radix].
AB  - Objective: To analyze the correlation between index components and climatic
      factors of Pseudostellariae Radix. Methods: Correlation analysis ( CA), partial
      least square (PLS) and PCA ordination were applied to analyze the correlation of
      index components in Pseudostellariae Radix and climatic factors, and to explore
      the main climatic factors affecting the accumulation of index components in
      Pseudostellariae Radix. Results: The origin and harvest time had influence on
      index components. The monthly minimum temperature, monthly average humidity,
      monthly precipitation and the annual precipitation were the dominant factors
      influencing the content of index components. Conclusion: Through the positive and
      negative correlation between climatic factors and index components, it could
      explain the rationality of traditional harvest time and the reason of high
      content of heterophyllin B in Pseudostellariae Radix from Jiangsu Jurong.

PMID- 30204373
TI  - [Identification and Fermentation Optimization of an Endophytic Fungus BLH34 with
      Antibacterial Activity from Macleaya cordata].
AB  - Objective: To identify an endophytic fungus BLH34 isolated from the leaf of
      Macleaya cordata with antibacterial activity,and to optimize its fermentation
      medium. Methods: Antimicrobial activity of an endophytic fungus BLH34 was
      determined by the cylinder plate method. The morphological characteristics and
      internal transcribed spacer( ITS) sequence were analyzed to identify the
      taxonomic position of the strain BLH34. The culture medium recipe was optimized
      by single factor and orthogonal experiment. Results: The results showed that the
      strain BLH34 had antimicrobial activity to the test strains,especially it showed
      significant inhibitory effect on Staphylococcus aureus. The strain BLH34 was
      identified as Penicillium turbatum,and the best culture medium recipe could be
      recognized as follows: 5% soluble starch,4% peptone,0. 06% NaNO3,and 0. 012%
      MgSO4.7H2O. Conclusion: The antimicrobial activity of crude extract was
      significantly increased after optimization, which could provide a basis for
      further separation and purification of the antibacterial substances extracted
      from strain BLH34.

PMID- 30204374
TI  - [UPLC Fingerprint of Gentiana officinalis Root].
AB  - Objective: To establish UPLC fingerprints of Gentiana officinalis root and
      Gentiana macrophylla root,and to evaluate the similarity of the fingerprints,in
      order to provide theoretical basis for the quality control of Gentiana
      officinalis root. Methods: The separation was performed on an ACQUITY UPLC~?BEH
      C18column( 50 mm * 2. 1 mm,1. 7 MUm) through a gradient elution of methanol-0.
      04% aqueous phosphoric at a flow rate of 0. 3 m L/min. The detection wavelength
      was 242 nm, and the column temperature was set at30 C. Similarity evaluation
      system for chromatographic fingerprint of TCM( Version 2004 A) was used to
      analyze the fingerprints. Results: 13 common peaks were selected as the
      fingerprint peaks from 13 batches of Gentiana officinalis root samples, with the
      similarities between 0. 976 to 0. 997, and Gentiana macrophylla root used for
      fingerprint applicability test has high similarity( 0. 998) with Gentiana
      officinalis root. Conclusion: This method with good precision and reliability
      should be used for the quality control of Gentiana officinalis root.

PMID- 30204375
TI  - [Histological Study on Integumentary and Digestive System of Hirudo nipponica].
AB  - Objective: The integumentary and digestive system of Hirudo nipponica were
      studied,in order to protect the precious Chinese herbal medicine. Methods: The
      histological study of integumentary and digestive system of Hirudo nipponica by
      histological methods were carried out by microscopical method. Results: The body
      wall of Hirudo nipponica could be divided into five layers, including cuticular
      layer, epithelial layer, dermis layer, muscle layer and grape-like tissue. The
      digestive system was composed ofmouth,pharyngeal,esophagus,crop,intestine,rectum
      and anus. Conclusion: This study can provide the basic data for the artificial
      breeding, research in pathology and physiological functions of Hirudo nipponica.

PMID- 30204378
TI  - [Effects of Volatile Oils from Different Preparations of Angelica sinensis Root
      on Acute Inflammation Induced by LPS in Rats].
AB  - Objective: To compare the intervention effects of volatile oils from different
      preparations of Angelica sinensis root on acute inflammation induced by
      lipopolysaccharide in rats. Methods: Acute inflammation model was induced by
      intraperitoneal injection of lipopolysaccharide( 100 MUg/kg) in rats. Blood and
      serum inflammatory mediators and cytokines were detected, combining with the
      pathological histological observation of lung and liver to evaluate the anti
      inflammatory activities of volatile oils from parching Angelica sinensis root
      with wine( J-VOAS),volatile oils from charred Angelica sinensis root( C-VOAS) and
      Angelica sinensis root( S-VOAS). Results: Compared with control group, the WBC
      count, the percentage of NE and PLT count in acute inflammation model group
      significantly increased ( P < 0. 05),and the percentage of LY significantly
      decreased( P < 0. 05); the content of IL-1beta,IL-6,NO and TNF-alpha
      significantly increased( P < 0. 001) and content of IL-10 significantly
      decreased( P < 0. 05) in model group; after J-VOAS,C-VOAS and S-VOAS
      intervention, the blood routine index and serum inflammatory mediators and
      cytokines significantly reversed( P < 0. 05). The pathological histological study
      showed that expanded alveoli, massive inflammatory cells infiltration in alveoli
      and pulmonary interstitium, the liver leaflets diffuse necrosis, hepatic cord
      derangement, and some of the liver cells degeneration and edema in model group;
      after J-VOAS intervention, their pathological changes significantly reduced.
      Conclusion: All volatile oils from different preparations of Angelica sinensis
      root had intervention on acute inflammation induced by LPS. And J-VOAS had the
      best effect, followed by C-VOAS and S-VOAS.

PMID- 30204379
TI  - [Pharmacological Effects of Different Prepared Typhonii Rhizoma].
AB  - Objective: To evaluate the different actions of crude and prepared Typhonii
      Rhizoma through pharmacological and statistical methods. Methods: Spontaneous
      activity test, sleep test, and seizure induced by dimefline in mice were used to
      examine the sedative and anticonvulsant effects of different prepared products of
      Typhonii Rhizoma. Twisting induced by acetic acid, law pain induced by
      formaldehyde, and ear swelling caused by xylene were applied to examine the anti
      inflammatory and analgesic effects of those different prepared products. Then the
      pharmacological effects of different prepared Typhonii Rhizoma were
      comprehensively analyzed by principal components analysis method. Results:
      Typhonii Rhizoma significantly reduced the spontaneous activities of mice,
      prolonged the convulsions latency,decreased twisting times, licking time and ear
      swelling. The principal components analysis results showed that the sample order
      from strong to weak was Typhonii Rhizoma prepared by ginger and alum, prepared by
      alum,crude Typhonii Rhizoma, and those prepared by ginger. Conclusion: Crude and
      prepared Typhonii Rhizoma exert sedative, anticonvulsant, analgesic and anti
      inflammatory effects in different degrees.

PMID- 30204380
TI  - [Chemical Constituents from the Roots of Macleaya cordata].
AB  - Objective: To investigate the chemical constituents from the roots of Macleaya
      cordata. Methods: The compounds were isolated and purified by silica
      gel,recrystallization and semi-preparative HPLC, their structures were
      eclucidated by physicochemistry properties, MS and NMR. Results: Seven compounds
      were isolated and identified as 6-cyanodihydrochelerythrine (1),6
      cyanodihydrochelilutine (2),dihydrochelirubine (3),6-methoxynorchelerythrine
      (4),dihydrosanguinarine (5),6-actonyldihydrosanguinarine (6) and stigmasterol
      (7). Conclusion: Compounds 1,2 are new natural compounds and compound 4 is
      obtained from Macleaya cordata for the first time.

PMID- 30204381
TI  - [LC/MS/MS Analysis of the Metabolites of Lathyrane Diterpenoids in Caco-2 Cells].
AB  - Objective: To identify the metabolites of euphorbetin L1,euphorbetin
      L2,euphorbetin L8 and 6( 17),12( E)-lathyrol-5,15-diacetate-3-phenylacetate in
      Caco-2 cells by LC/MS/MS. Methods: Caco-2 cells were cultured with 100 MUg/mol
      lathyrane diterpenoid for 3,6,12 h,respectively. Then the samples were
      collected,purified and identified by LC/MS/MS. Results: The major metabolites of
      euphorbetin L1 were two methylated products which were obtained after hydrolysis
      of the ester. The major metabolites of euphorbetin L2,euphorbetin L8 and 6(
      17),12( E)-lathyrol-5,15-diacetate-3-phenylacetate were hydrolysis products of
      the ester. Conclusion: The main metabolic pathway of euphorbetin L1 is
      methylation and hydrolysis of the ester. The main metabolic pathway of
      euphorbetin L2,euphorbetin L8 and 6( 17),12( E)-lathyrol-5,15-diacetate-3
      phenylacetate is hydrolysis of the ester. LC/MS/MS can identify the metabolites
      of euphorbetin L1,euphorbetin L2,euphorbetin L8 and 6( 17),12( E)-lathyrol-5,15
      diacetate-3-phenylacetate in Caco-2 cells quickly and sensitively.

PMID- 30204382
TI  - [Chemical Constituents of the Endophytic Fungus Rhinocladiella sp. lgt-3 from
      Tripterygium wilfordii].
AB  - Objective: To study the chemical constituents and monoamine oxidase inhibitory
      activity of Rhinocladiella sp. lgt-3,which was an endophytic fungus isolated from
      Tripterygium wilfordii. Methods: Compounds were isolated from by various column
      chromatography. The structures were elucidated by various spectral data. The
      activity was tested by using 96-well micro-plated method. Results: 10 compounds
      were isolated and identified as 3,4-dihydro-3,4,8-trihydroxy-1( 2H)
      naphthalenone( 1),( 3R,4R)-4-hydroxymellein( 2),O-methylmellein( 3),4-( 2
      hydroxybutynoxy) benzoic acid( 4),2,4-dihydroxy-6-(( R)-4-hydroxy-2-oxopentyl)-3
      methylbenzaldehyde( 5),( Z)-N-( 4-hydroxystyryl) formamide( 6), aspterric acid(
      7),bufotenin( 8),5-hydroxy-N,N-dimethyltryptamine-N-oxide( 9)and 5-methoxy-N,N
      dimethyltryptamine( 10). Compounds 1,8 ~ 10 showed moderate anti-monoamine
      oxidase activity with IC50 values of 32,36,50,56 MUmol/L, respectively.
      Conclusion: Compounds 3 ~ 10 are isolated from Rhinocladiella genus for the first
      time and the anti-monoamine oxidase activity of compound 1 are reported for the
      first time.

PMID- 30204383
TI  - [Chemical Constituents from Jasminum elongatum].
AB  - Objective: To investigate the chemical constituents of Jasminum elongatum.
      Methods: The chemical constituents were isolated and purified by various column
      chromatographic methods and preparative HPLC. Their structures were identified by
      physicochemical properties and spectral analysis. Results: Nine compounds were
      isolated from the methanol extract of Jasminum elongatum and identified as
      protocatechuic acid( 1),caffeic acid( 2),salicylic acid( 3),isovanillic acid(
      4),ferulic acid( 5),methyl caffeate( 6),caffein( 7),3,6-diisopropylpiperazin-2,5
      dione( 8),scopoletin( 9). Conclusion: All the compounds are isolated from the
      this plants for the first time.

PMID- 30204384
TI  - [Research on Chemical Constituents and Anti-tumor Activity of Eupatorium
      chinense].
AB  - Objective: To study the chemical constituents and their anti-tumor activity of
      Eupatorium chinense. Methods: The chemical constituents were separated and
      purified by the normal phase silica gel column chromatography,preparative thin
      layer chromatography,and preparative HPLC. Their structures were determined by
      various spectral data,their antitumor activity in vitro was determined by MTT
      assay. Results: Six compounds were isolated from the ethyl acetate extract of
      Eupatorium chinense,and the structures were identified as eupalinilide G(
      1),8beta-( 4'-hydroxytigloyloxy)-5-desoxy-8-desacyleuparotin( 2),3-(
      hydroxymethyl)-1,13,14,15-tetrahydroxy-7,11,15-trimethyl-2,6,10-hexadecatriene(
      3),3-( hydroxymethyl)-1,13,15-trihydroxy-7,11,15-trimethyl-2,6,10-hexadecatrien
      14-yl acetate( 4),eupafolin( 5) and hiyodorilactone B( 6). Compound 2 showed
      cytotoxicity against HGC-27 and B16 cancer cell lines with IC50 values of 4. 29
      MUg/m L and 5. 53 MUg/m L,respectively. Methods: The chemical constituents were
      separated and purified by the normal phase silica gel column
      chromatography,preparative thin-layer chromatography,and preparative HPLC. Their
      structures were determined by various spectral data,their antitumor activity in
      vitro was determined by MTT assay. Results: Six compounds were isolated from the
      ethyl acetate extract of Eupatorium chinense,and the structures were identified
      as eupalinilide G( 1),8beta-( 4'-hydroxytigloyloxy)-5-desoxy-8-desacyleuparotin(
      2),3-( hydroxymethyl)-1,13,14,15-tetrahydroxy-7,11,15-trimethyl-2,6,10
      hexadecatriene( 3),3-( hydroxymethyl)-1,13,15-trihydroxy-7,11,15-trimethyl-2,6,10
      hexadecatrien-14-yl acetate( 4),eupafolin( 5) and hiyodorilactone B( 6). Compound
      2 showed cytotoxicity against HGC-27 and B16 cancer cell lines with IC50 values
      of 4. 29 MUg/m L and 5. 53 MUg/m L,respectively. Conclusion: Compounds 2 ~ 5 are
      isolated from the Eupatorium chinense for the first time,and compound 2 has
      significant cytotoxic activity against HGC-27 cell line.

PMID- 30204385
TI  - [Chemical Constituents from Infructescence of Platycarya strobilacea].
AB  - Objective: To study the chemical constituents of the chloroform and acetic ether
      fractions from infructescence of Platycarya strobilacea. Methods: The compounds
      were isolated and purified by various chromatographic methods. Spectral analysis
      were taken to identify the structures. Results: Eleven compounds were isolated
      and identified as dotriacontane( 1), ursolic acid( 2),hexacosene( 3),beta
      sitosterol( 4),daucosterol( 5),2,5,8-trihydroxy-3-methoxy-1,4-naphthalenedione(
      6),3,3'-dimethoxyellagic acid( 7),ellagic acid( 8),4'-hydroxyisoflavone-7-O-beta
      D-galactoside( 9),3,3'-dimethoxyellagic acid-4'-O-beta-D-xylopyroside( 10),
      gallic acid( 11). Conclusion: Compounds 1,3 ~ 6,9,10 are isolated from this genus
      for the first time, compounds 1 ~ 6,9,10 are isolated from this plant for the
      first time.

PMID- 30204386
TI  - [Chemical Constituents from the Roots of Lindera glauca and Their Antitumor
      Activity on Four Different Cancer Cell Lines].
AB  - Objective: To study the chemical constitutes from the roots of Lindera glauca and
      the alkaloids influence on proliferation of HT-29,SGC-7901,SMMC-7721 and A549
      cell lines. Methods: The constituents were isolated by column chromatography such
      as RP-18,Sephadex LH-20 and silica gel,and their structures were elucidated by
      spectroscopic data analysis and compared with literature data. The antitumor
      activity was determined by MTT assay. Results: Ten compounds had been isolated
      and identified as(-)-magnocurarine( 1),N-methyl-laurotetanine( 2),laurotetanine(
      3),( +)-boldine( 4),(-)-norisoboldine( 5),( +)-norisocorydine( 6),pmethane-3,8
      trans-diol( 7),p-methane-3,8-cis-diol( 8),eudesm-4( 15)-ene-7,11-diol( 9) and
      4beta,6beta-dihydroxy-1alpha,5beta( H)-guai-9-ene( 10). Compounds 2 ~ 4 showed
      significant inhibitory activities against HT-29,SGC-7901,SMMC-7721 and A549
      cells. Conclusion: Compound 1,9 and 10 are isolated from this plant for the first
      time. The IC50 value of compound 2 against HT-29 and SGC-7901 cell lines is even
      lower than VP-16.

PMID- 30204387
TI  - [Study on Chemical Constituents and Content Determination of Feifukang Mistura].
AB  - Objective: To identify the main chemical constituents and to determine the
      content in Feifukang mistura. Methods: HPLC-MS technique was used to profile and
      identify the chemical constituents by comparing the retention time,MS data with
      the reference standard. The content determination of all the chemical
      constituents were carried on a HPLC system. Results: Five compounds were
      separated from Feifukang mistura,which were identified as
      neomangiferin,mangiferin,calycosin-7-O-glucoside,calycosin,and schizandrol A. The
      standard curves of them showed good linearity on the range of 2. 08 ~ 104. 0
      MUg/m L,2. 00 ~ 100. 0 MUg/m L,2. 00 ~ 100. 0MUg/m L,2. 09 ~ 104. 5 MUg/m L,and
      1. 98 ~ 99. 0 MUg/m L,respectively. The average recoveries were all in the range
      of 91. 3 ~ 103. 8%. Conclusion: The methods of chemical constituents
      identification and content determination were established,which may offer better
      revealing the material basis and controlling quality of Feifukang mistura.

PMID- 30204388
TI  - [Study on Quality Evaluation of Ophiopogonis Radix in Sichuan].
AB  - Objective: To evaluate the quality of Ophiopogonis Radix from produce area,
      circulation link and clinical application in Sichuan, and to provide the
      theoretical basis for the quality control of Ophiopogonis Radix in Sichuan.
      Methods: 105 samples were collected from different produce area, market, factory
      of decoction pieces, drugstore in Sichuan. The content of moisture,total ash,
      extractum, total saponin, heavy metal, harmful element, pesticide residues,
      sulfur dioxide were measured by the methods which recorded in Chinese
      pharmacopoeia. The content of ophiopogonin D, methylophiopogonanone A,
      methylophiopogonanone B were measured by HPLC. Results: The content of moisture,
      total ash, extractum, total saponin in 105 samples Ophiopogonis Radix in Sichuan
      were at 5. 7%~ 17. 9%,0. 9% ~ 3. 4%,68. 7% ~ 95. 1%,0. 12% ~ 0. 57%,respectively.
      Over standard rate of sulfur dioxide was 23. 81%. The content of heavy metal and
      harmful element was conform to the limitation requirement of Chinese
      pharmacopoeia. Three kinds of organic pesticide had not been checked out. The
      content of ophiopogonin D, methylophiopogonanone A,methylophiopogonanone B were
      at 0. 04~ 0. 30 mg/kg,0. 0170 ~ 0. 0837 mg/kg,0. 0049 ~ 0. 0370 mg/kg,
      respectively. Conclusion: The quality of 105 samples are up to the requirement
      with the provisions of the Chinese pharmacopoeia. Actually,the mandatory standard
      was not perfect, especially lack of standard in security. It is suggested that
      strengthening supervision of sulfur dioxide and paclobutrazol residual according
      to the actual situation for ensuring the safe and effective of Ophiopogonis Radix
      in clinical application.

PMID- 30204389
TI  - [Optimization of Extracting Technology of Saponins in Steamed Panax notoginseng
      by Box-Behnken Design and Response Surface Methodology].
AB  - Objective: To optimize the extraction process of saponins in steamed Panax
      notoginseng by Box-Behnken design-response surface methodology. Methods: On the
      basis of single factor screening, Box-Behnken experimental design was
      employed,the content of saponins and dry extract rate of overall desirability(
      OD) were as the evaluation index,and the extraction time( X1),solvent multiple(
      X2),solvent concentration( X3) and extraction times were used as independent
      variables. Optimum experimental condition were selected from the stationary point
      of the response surfaces. Results: By Box-Behnken design-response surface
      methodology and prognostic scoring system optimized scheme,the preferred
      processing condition were as follows, the right amount of steamed Panax
      notoginseng,added 16 times of 70% ethyl alcohol,extracted three times,and each
      time extracted for 2. 5 h. The calculated value of the process condition was
      basically consistent with the theoretical value,with less deviation. Conclusion:
      The extraction technology of saponins optimized by Box-Behnken design is
      practical and rational,which can better predict the content of saponins and dry
      extract rate and other indicators in steamed Panax notoginseng.

PMID- 30204390
TI  - [The effect of Salvianolic Acid B on the Apoptosis of HUVECs Induced by
      Intermittent High Glucose].
AB  - Objective: To investigate the effect of Salvianolic acid B (Sal B) on the
      apoptosis of human umbilical vein endothelial cells (HUVECs) induced by
      intermittent high glucose and to explore the possible mechanisms. Methods: HUVECs
      were preincubated with Sal B for 24 h, followed by incubation with intermittent
      high glucose (IHG, 5.5 mmol/L 12 h, 33.3 mmol/L 12 h) for 72 h. The viability of
      the HUVECs was determined by MTT assay, and the cells apoptosis was measured flow
      cytometry, respectively. The levels of nitric oxide (NO), total antioxidant
      capacity (T-AOC), malondialdehyde (MDA), and Caspase-3 activity were determined
      by colorimetric method. Intracellular ROS was evaluated by fluorescent
      microscopy. The protein levels of NOX4, p-eNOS, BAX, and BCL-2 were determined by
      Western-blot. Results: Pretreatment with Sal B significantly ameliorated IHG
      induced cells injury as was manifested by increased cell viability, up-regulated
      eNOS activation, and promoted the release of NO in HUVECs (P < 0.05 or P < 0.01).
      Sal B evidently suppressed IHG-induced cell apoptosis, down-regulated the
      expression of BAX protein and up-regulated the expression of BCL-2 protein. The
      activity of Capase-3 was also significantly reduced. Pre-incubation with Sal B
      led to a significant enhancement of antioxidant capacity and a reduction of NOX4
      protein expression, accompanied by a remarkable decrease of intracellular ROS and
      MDA content (P < 0.05 or P < 0.01). Conclusion: Sal B is capable of suppressing
      IHG-induced injury and apoptosis in HUVECs, which might be attributed to the
      attenuation of oxidative stress, regulation of BCL-2/BAX protein expression, and
      subsequent suppression of Caspase-3 activity.

PMID- 30204391
TI  - [Tissue Distribution of Alkaloids from Coptidis Rhizoma in Rats Determined by
      UPLC-MS].
AB  - Objective: To develop an UPLC-MS method for simultaneous determination of
      alkaloids from Coptidis Rhizoma in rat tissues, and to study the tissue
      distribution of alkaloids from Coptidis Rhizoma in rats. Methods: The samples
      were extracted with ethyl acetate, and analyzed by UPLC-MS with acetonitrile-0.
      2% formic acid solution in a gradient elution mobile phase, the flow rate was 0.
      2m L/min. Tetrahydropalmatine was used as an internal standard. The mass
      spectrometer was operated in selected reaction monitoring( SIM) mode with
      positive electrospray ionization, the transition were m/z 191. 904 /118. 973(
      noroxyhydrastinine), m/z 335. 877 /308. 072( 8-ocoptisine),m/z 351. 94 /294. 554(
      palmatine chloride),m/z 335. 94 /262. 112( epiberberine), m/z 337. 94 /322. 422(
      columbamine), m/z 319. 904 /292. 037( coptisine), m/z 355. 977 /192. 036(
      tetrahydropalmatine),m/z 335. 94 /320. 036( berberine hydrochloride),m/z 351. 94
      /321. 995( oxyberberin), m/z 337. 94 /322. 949( jatrorrhizine respectively).
      Results: Excellent linearity was observed in all alkaloids in their linear range(
      r & 0. 9901). The RSD of precision of the developed method was less than 15%,and
      the accuracy and stability were less than +/- 15%,the extraction recovery was 72.
      1% ~ 82. 9% with RSD less than 15%.
      Coptisine,epiberberine,berberine,jatrorrhizine,columbamine,palmatine were widely
      distributed in rat tissues. Noroxyhydrastinine,8-ocoptisine,oxyberberin could
      only be determined in liver and heart or kidney. Conclusion: The established
      method is simple and accurate. Satisfactory results are obtained with applying
      this method to the tissue distribution study of alkaloids from Coptidis Rhizoma.

PMID- 30204392
TI  - [Effect of two Treatments of Sophoridine on TLR4-JNK Signaling Pathway of
      RAW264.7 Cells Induced by LPS].
AB  - Objective: To observe the effect of two treatments of sophoridine( pretreating
      and premixing) on lipopolysaccharide( LPS)-induced on TLR4,the expression of TLR4
      and its downstream signaling molecule such as JNK and c-jun in RAW264. 7 cells
      were,and to detect its mechanism. Methods: RAW264. 7 cells were randomly divided
      into five groups,RAW264. 7 cells control group added absence serum DMEM to
      incubate cells; LPS group, with added 100 MUg/L LPS DMEM to incubate cells;
      Sophoridine control group added 31. 25 mg/L sophoridine DMEM to incubate cells;
      sophoridine pretreating group,added 31. 25 mg/L sophoridine DMEM to incubate
      cells 24 h,then threw away sophoridine and added 100 MUg/L LPS DMEM to incubate
      cells; sophoridine premixing group added the final concentration of 31. 25 mg/L
      sophoridine and 100 MUg/L LPS DMEM to incubate cells 1 h. After above treatments,
      collected cells at 5,30,60,and 120 min,respectively. The mRNA expressions of
      TLR4,JNK and c-jun were determined by reverse transcription PCR( RT-PCR),the
      protein expression of c-jun in RAW264. 7 cells was measured by
      immunocytochemistry and Western blot. Results: Compared with RAW264. 7 cells
      control group, there were no statistical difference on each index in sophoridine
      control group( P >0. 05),the mRNA expressions of TLR4,JNK,c-jun and c-jun protein
      expression were significantly increased in LPS group( P < 0. 01 or P < 0. 05),but
      each index increased were different at different time points; the mRNA
      expressions of TLR4,JNK,c-jun and c-jun protein expression in RAW264. 7 cells
      were lower in sophoridine pretreating and premixing group than LPS group, but
      each index decreased were different at different time points. Conclusion:
      Sophoridine induces the effect of antiendotoxin through regulating TLR4-JNK
      signal transduction pathway, which showing that the effect of different
      treatments of sophoridine may be multi-link adjustment.

PMID- 30204393
TI  - [Study on Filtrating Separated Constituents of Epimedii Folium Based on Its Anti
      osteoporosis].
AB  - Objective: To investigate the pharmacological effects of Epimedii Folium and its
      different separate compositions on the rats with RA-induced osteoporosis and to
      screen the most active constituent. Methods: With the establishment of animal
      model of osteoporotic rats induced by RA, the efftects of different constituents
      extracted from Epimedii Folium on the contents of Ca2+, P3+, ALP, StrACP, BCG and
      E2 in serum were measured, and their influence on the calcium and phosphate of
      bone, bilateral femur mass/body mass, unilateral femur ash mass/dry mass was
      evaluated. The femur morphology was observed through histomorphology. Results:
      The 30% ethanol section can significantly increase the contents of Ca2+, P3+ in
      model rats, promote the level of E2 in serum, and decrease the contents of ALP,
      StrACP, BCG and P3+ in serum, significantly raising the unilateral femur ash
      mass/dry mass and bilateral femur mass/body mass. The total constituents can
      significantly increase Ca2+, unilateral femur ash mass/dry mass, and
      unilateralbilateral femur mass/body mass, and decrease ALP and P3+ in serum. In
      comparing with other groups, except for the positive control group, the
      observation of histomorphology exhibited that the 30% ethanol section improved
      the pathomorphism of bone most obviously and significantly increased the density
      and space of trabecular, with discontinuous spongy bone existing in local
      gusongzhiincus buttress. The sequence of the effect on anti-osteoporosis was 30%
      ethanol section > total constituents > water section > 95% ethanol section >
      polysaccharide. Conclusion: The 30% ethanol section manifested the most
      significant effect on anti-osteoporosis. The total constituents also had a
      certain degree of effect on anti-osteoporosis which was weaker than 30% ethanol
      section. The water and 95% ethanol sections showed a certain extent of preventive
      effect on anti-osteoporosis, and the effects of polysaccharide group were
      inapparent.Objective:To investigate the pharmacological effects of Epimedii
      Folium and its different extacted constituents on the rats with RA-induced
      osteoporosis.To screening the most active constituent. Methods: With building
      animal model of osteoporotic rat induced by RA, different constituents extracted
      from Epimedii Folium affected the content of Ca2+,P3+,ALP,Str ACP,BCG and E2in
      serum were measured, and on the calcium and phosphate of bone,mass-ratio of in
      bilateral femur, ash to dry ratio in unilateral were evaluated. The thigh-bone
      morphological was observed through histomorphology. Results: The 30%alcohol
      section can significantly increase the content of Ca2+,P3+in model rats, promote
      the level of E2in serum, and decrease the content of Str ACP,BCG and P3+in serum,
      significantly raise the mass-ratio of in bilateral femur, and ash to dry in
      unilateral. The entire ingredient section can significantly increase Ca2+,mass
      ratio of in bilateral femur, and ash to dry in unilateral, decrease ALP and P3+in
      serum. In comparing with other groups, except for the positive control group, the
      observation of histomorphology exhibit that the 30%alcohol section improved the
      pathomorphism of bone most obviously and significantly increased the density and
      space of trabecular, with discontinuous spongy bone existing in local
      gusongzhiincus buttress. The sequence for anti-osteoporosis was 30%alcohol
      section>entire ingredien>water section>95%alcohol section>polysaccharide.
      Conclusion: The 30%alcohol section manifests the most significant effect on anti
      osteoporosis. The entire ingredient section also has a certain degree of effect
      on anti-osteoporosis but weaker than 30%alchol section. The water and 95%alcohol
      sections show a certain extent of preventive effect on anti-osteoporosis, and the
      effects of polysaccharide group are inapparent.

PMID- 30204399
TI  - Ultratough, Self-Healing, and Tissue-Adhesive Hydrogel for Wound Dressing.
AB  - A hydrogel for potential applications in wound dressing should possess several
      peculiar properties, such as efficient self-healing ability and mechanical
      toughness, so as to repair muscle and skin damage. Additionally, excellent cell
      affinity and tissue adhesiveness are also necessary for the hydrogel to integrate
      with the wound tissue in practical applications. Herein, an ultratough and self
      healing hydrogel with superior cell affinity and tissue adhesiveness is prepared.
      The self-healing ability of the hydrogel is obtained through hydrogen bonds and
      dynamic Schiff cross-linking between dopamine-grafted oxidized sodium alginate
      (OSA-DA) and polyacrylamide (PAM) chains. The covalent cross-linking is
      responsible for its stable mechanical structure. The combination of physical and
      chemical cross-linking contributes to a novel hydrogel with efficient self
      healing ability (80% mechanical recovery in 6 h), high tensile strength (0.109
      MPa), and ultrastretchability (2550%), which are highly desirable properties and
      are superior to previously reported tough and self-healing hydrogels for wound
      dressing applications. More remarkably, due to plenty of catechol groups on the
      OSA-DA chains, the hydrogel has unique cell affinity and tissue adhesiveness.
      Moreover, we demonstrate the practical utility of our fabricated hydrogel via
      both in vivo and in vitro experiments.

PMID- 30204400
TI  - Biofunctionalization of Sub-Diffractionally Patterned Polymer Structures by
      Photobleaching.
AB  - Stimulated emission depletion (STED) nanolithography allows nanofabrication below
      the diffraction limit. Recently, it was applied to nanoanchors for protein
      fixation down to the single molecule level. We now combined STED nanolithography
      with laser-assisted protein adsorption by photobleaching (LAPAP) for optical and
      selective attachment of proteins to subdiffractional structures. In turn, STED
      was used for imaging of fluorescently tagged streptavidin to reveal protein
      binding to STED-lithographically patterned acrylate structures via LAPAP. Protein
      localization down to 56 nm spots was achieved using all-optical methods at
      visible wavelengths.

PMID- 30204401
TI  - Microneedle-Mediated Delivery of Lipid-Coated Cisplatin Nanoparticles for
      Efficient and Safe Cancer Therapy.
AB  - Cisplatin is the first-line chemotherapeutic agent, but its systemic toxicity and
      side effects severely limit its clinical use. We report a microneedle technique
      to mediate the transdermal delivery of lipid-coated cisplatin nanoparticles (LCC
      NPs) for efficient and safe cancer therapy. Cisplatin was encapsulated by tumor
      targeting pH-responsive lipid nanoparticles with a high loading rate of 80%, and
      the encapsulation substantially increased the solubility of cisplatin and
      enhanced its antitumor efficiency in vitro. The LCC-NPs were embedded in
      dissolvable microneedles, and released from the microneedles after inserting into
      the skin. This enabled the nanoparticles to pass the stratum corneum for safe
      local delivery. An in vivo study with a xenograft tumor animal model demonstrated
      that microneedle arrays loaded with cisplatin nanoparticles significantly
      increased cytotoxicity and apoptosis in cancer cells with an apoptotic index of
      58.6%, resulting in significantly reduced tumor volume and weight. Moreover,
      serum platinum, pulmonary toxicity, hepatotoxicity, and nephrotoxicity were not
      detected in vivo, indicating that this technique is biosafe. The cisplatin
      nanoparticle microneedle system developed in this study may offer promising
      opportunities in cancer therapy for enhancing antitumor effects and reducing
      systemic toxicity and side effects.

PMID- 30204402
TI  - Protein Nanofibril Assemblies Templated by Graphene Oxide Nanosheets Accelerate
      Early Cell Adhesion and Induce Osteogenic Differentiation of Human Mesenchymal
      Stem Cells.
AB  - Bombyx mori silk fibroin (SF) is a promising natural biocompatible protein.
      However, its interaction with graphene oxide (GO) has never been studied and the
      resultant SF/GO matrix has not been used to direct stem cell fate. Herein, we
      found out that mixing SF molecules and GO nanosheets in an aqueous solution can
      trigger the assembly of SF nanoparticles into oriented nanofibrils due to the
      guidance of GO nanosheets, forming SF/GO films with unique nanotopographies and
      improved modulus upon the removal of the solvent. When GO mass percentage in the
      SF/GO films is 2 and 10%, the SF assemblies are necklace-like nanofibrils
      (assembled from loosely linked SF nanoparticles) and solid nanofibrils (assembled
      from densely linked SF nanoparticles) in the resultant films, termed SG2 and
      SG10, respectively. GO nanosheets guided the SF assembly into nanofibrils by
      triggering the structural change of SF molecules from random coils to beta
      sheets, as confirmed by Fourier transform infrared spectroscopy and circular
      dichroism measurements. Furthermore, oxidative groups in the GO nanosheets were
      reduced by the reducing groups in SF during the nanofibril formation according to
      X-ray photoelectron spectroscopy and Raman spectroscopy. The reduction of the
      oxidative groups in GO by SF was further verified by the good cell viability on
      the SF/GO films. The unique nanotopographies of the SF/GO films were found to
      accelerate the early cell adhesion and induce the osteogenic differentiation of
      human mesenchymal stem cells (MSCs) even in the absence of additional inducers in
      the medium. More importantly, SG10 presents a stronger capability in promoting
      early MSC adhesion by promoting F-actin assembly, increasing cell spreading area,
      and inducing the osteogenic differentiation of the MSCs by the unique SF/GO
      nanofibrous matrix. To the best of our knowledge, it is the first report that the
      SF/GO substrates can induce the osteogenic differentiation of MSCs in the absence
      of osteogenic differentiation medium. Therefore, SF/GO composite materials would
      have a potential application in the field of bone tissue engineering.

PMID- 30204403
TI  - Three-Dimensionally Printed Silk-Sericin-Based Hydrogel Scaffold: A Promising
      Visualized Dressing Material for Real-Time Monitoring of Wounds.
AB  - A wound dressing which can be convenient for real-time monitoring of wounds is
      particularly attractive and user-friendly. In this study, a nature-originated
      silk-sericin-based (SS-based) transparent hydrogel scaffold was prepared and
      evaluated for the visualization of wound care. The scaffold was fabricated from a
      hybrid interpenetrating-network (IPN) hydrogel composed of SS and methacrylic
      anhydride-modified gelatin (GelMA) by 3D printing. The scaffold transformed into
      a highly transparent hydrogel upon swelling in PBS, and thus, anything underneath
      could be easily read. The scaffold had a high degree of swelling and presented a
      regularly macroporous structure with pores around 400 MUm * 400 MUm, which can
      help maintain the moist and apinoid environment for wound healing. Meanwhile, the
      scaffolds were conducive to adhesion and proliferation of L929 cells. A coculture
      of HaCaT and HSF cells on the scaffold showed centralized proliferation of the
      two cells in distributed layers, respectively, denoting a promising comfortable
      environment for re-epithelialization. Moreover, in vivo studies demonstrated that
      the scaffold showed no excessive inflammatory reaction. In short, this work
      presented an SS-based transparent hydrogel scaffold with steerable physical
      properties and excellent biocompatibility through 3D printing, pioneering
      promising applications in the visualization of wound care and drug delivery.

PMID- 30204404
TI  - Protein Nanostructures Produce Self-Adjusting Hyperpolarized Magnetic Resonance
      Imaging Contrast through Physical Gas Partitioning.
AB  - Signal amplification strategies are critical for overcoming the intrinsically
      poor sensitivity of nuclear magnetic resonance (NMR) reporters in noninvasive
      molecular detection. A mechanism widely used for signal enhancement is chemical
      exchange saturation transfer (CEST) of nuclei between a dilute sensing pool and
      an abundant detection pool. However, the dependence of CEST amplification on the
      relative size of these spin pools confounds quantitative molecular detection with
      a larger detection pool typically making saturation transfer less efficient. Here
      we show that a recently discovered class of genetically encoded nanoscale
      reporters for 129Xe magnetic resonance overcomes this fundamental limitation
      through an elastic binding capacity for NMR-active nuclei. This approach pairs
      high signal amplification from hyperpolarized spins with ideal, self-adjusting
      saturation transfer behavior as the overall spin ensemble changes in size. These
      reporters are based on gas vesicles, i.e., microbe-derived, gas-filled protein
      nanostructures. We show that the xenon fraction that partitions into gas vesicles
      follows the ideal gas law, allowing the signal transfer under hyperpolarized
      xenon chemical exchange saturation transfer (Hyper-CEST) imaging to scale
      linearly with the total xenon ensemble. This conceptually distinct elastic
      response allows the production of quantitative signal contrast that is robust to
      variability in the concentration of xenon, enabling virtually unlimited
      improvement in absolute contrast with increased xenon delivery, and establishing
      a unique principle of operation for contrast agent development in emerging
      biochemical and in vivo applications of hyperpolarized NMR and magnetic resonance
      imaging.

PMID- 30204406
TI  - Analyte-Responsive Hydrogels: Intelligent Materials for Biosensing and Drug
      Delivery.

PMID- 30204405
TI  - Temporal Response of Ionic Current Blockade in Solid-State Nanopores.
AB  - Signal delay is a crucial factor in resistive pulse analyses using low-thickness
      to-diameter aspect-ratio pores that aim to detect fine features in the ionic
      current blockade during the fast translocation of individual analytes to attain
      single-molecule tomography. Here we report on evaluations of the ionic current
      response to dynamic motions of nanoparticles in ultrathin solid-state nanopores.
      We systematically investigated the effects of pore resistance and membrane
      capacitance on resistive pulse waveforms under different salt concentration
      conditions and device configurations. The results revealed substantial
      modifications in the resistive pulse waveforms due to a slow charging/discharging
      processes at the water-touching thin dielectrics in the solid-state nanopore
      chips. We also provide a device design to improve the temporal resolution without
      compromising the spatial sensitivity. The present findings offer a breakthrough
      toward nanoporescopy to measure the nanoscopic shape of single-bioparticles and 
      molecules in electrolyte solution.

PMID- 30204407
TI  - Biotemplating Growth of Nepenthes-like N-Doped Graphene as a Bifunctional
      Polysulfide Scavenger for Li-S Batteries.
AB  - The practical application of lithium-sulfur (Li-S) batteries is hindered by their
      poor cycling stabilities that primarily stem from the "shuttle" of dissolved
      lithium polysulfides. Here, we develop a nepenthes-like N-doped hierarchical
      graphene (NHG)-based separator to realize an efficient polysulfide scavenger for
      Li-S batteries. The 3D textural porous NHG architectures are realized by our
      designed biotemplating chemical vapor deposition (CVD) approach via the
      employment of naturally abundant diatomite as the growth substrate. Benefiting
      from the high surface area, devious inner-channel structure, and abundant
      nitrogen doping of CVD-grown NHG frameworks, the derived separator favorably
      synergizes bifunctionality of physical confinement and chemical immobilization
      toward polysulfides, accompanied by smooth lithium ion diffusions. Accordingly,
      the batteries with the NHG-based separator delivers an initial capacity of 868
      mAh g-1 with an average capacity decay of only 0.067% per cycle at 2 C for 800
      cycles. A capacity of 805 mAh g-1 can further be achieved at a high sulfur
      loading of ~7.2 mg cm-2. The present study demonstrates the potential in
      constructing high-energy and long-life Li-S batteries upon separator
      modification.

PMID- 30204409
TI  - Molecular Basis for Autocatalytic Backbone N-Methylation in RiPP Natural Product
      Biosynthesis.
AB  - N-methylation of nucleic acids, proteins, and peptides is a chemical modification
      with significant impact on biological regulation. Despite the simplicity of the
      structural change, N-methylation can influence diverse functions including
      epigenetics, protein complex formation, and microtubule stability. While there
      are limited examples of N-methylation of the alpha-amino group of bacterial and
      eukaryotic proteins, there are no examples of catalysts that carry out post
      translation methylation of backbone amides in proteins or peptides. Recent
      studies have identified enzymes that catalyze backbone N-methylation on a peptide
      substrate, a reaction with little biochemical precedent, in a family of
      ribosomally synthesized natural products produced in basidiomycetes. Here, we
      describe the crystal structures of Dendrothele bispora dbOphMA, a
      methyltransferase that catalyzes multiple N-methylations on the peptide backbone.
      We further carry out biochemical studies of this catalyst to determine the
      molecular details that promote this unusual chemical transformation. The
      structural and biochemical framework described here could facilitate
      biotechnological applications of catalysts for the rapid production of backbone N
      methylated peptides.

PMID- 30204408
TI  - Greener Luminescent Solar Concentrators with High Loading Contents Based on in
      Situ Cross-Linked Carbon Nanodots for Enhancing Solar Energy Harvesting and
      Resisting Concentration-Induced Quenching.
AB  - A luminescent solar concentrator (LSC) is composed of loaded luminophores and a
      waveguide that can be employed to harvest and concentrate both direct and
      diffused sunlight for promising applications in solar windows. Thus far, most of
      efficient LSCs still relied on the heavy-metal-containing colloidal quantum dots
      (CQDs) dispersed into a polymer matrix with a very low loading (typically <1 wt
      %). Such low-loading constraint is required to mitigate the concentration-induced
      quenching (CIQ) and maintain high optical quality and film uniformity, but this
      would strongly reduce the light-absorbing efficiency. To address all issues,
      greener LSCs with high loading concentration were prepared by in situ cross
      linking organosilane-functionalized carbon nanodots (Si-CNDs), and their
      photophysical properties relevant to LSC operation were studied. The PL emission
      is stable and does not suffer from the severe CIQ effect for cross-linked Si-CNDs
      even with 25 wt % loadings, thus exhibiting high solid-state quantum yields (QYs)
      up to 45 +/- 5% after the calibration of the reabsorption losses. Furthermore,
      such LSCs can still hold high optical quality and film uniformity, leading to low
      scattering losses and high internal quantum efficiency of ~22%. However, the
      reabsorption losses need to be further addressed to realize large-area LSCs based
      on earth-abundant, cost-effective CNDs.

PMID- 30204410
TI  - Field-Effect Device Using Quasi-Two-Dimensional Electron Gas in Mass-Producible
      Atomic-Layer-Deposited Al2O3/TiO2 Ultrathin (<10 nm) Film Heterostructures.
AB  - We report the field-effect transistors using quasi-two-dimensional electron gas
      generated at an ultrathin (~10 nm) Al2O3/TiO2 heterostructure interface grown via
      atomic layer deposition (ALD) on a SiO2/Si substrate without using a single
      crystal substrate. The 2DEG at the Al2O3/TiO2 interface originates from oxygen
      vacancies generated at the surface of the TiO2 bottom layer during ALD of the
      Al2O3 overlayer. High-density electrons (~1014 cm-2) are confined within a ~2.2
      nm distance from the Al2O3/TiO2 interface, resulting in a high on-current of ~12
      MUA/MUm. The ultrathin TiO2 bottom layer is easy to fully deplete, allowing an
      extremely low off-current, a high on/off current ratio over 108, and a low
      subthreshold swing of ~100 mV/decade. Via the implementation of ALD, a mature
      thin-film process can facilitate mass production as well as three-dimensional
      integration of the devices.

PMID- 30204411
TI  - Aggregation of Vibrio cholerae by Cationic Polymers Enhances Quorum Sensing but
      Overrides Biofilm Dissipation in Response to Autoinduction.
AB  - Vibrio cholerae is a Gram-negative bacterium found in aquatic environments and a
      human pathogen of global significance. Its transition between host-associated and
      environmental lifestyles involves the tight regulation of niche-specific
      phenotypes such as motility, biofilm formation, and virulence. V. cholerae's
      transition from the host to environmental dispersal usually involves suppression
      of virulence and dispersion of biofilm communities. In contrast to this naturally
      occurring transition, bacterial aggregation by cationic polymers triggers a
      unique response, which is to suppress virulence gene expression while also
      triggering biofilm formation by V. cholerae, an artificial combination of traits
      that is potentially very useful to bind and neutralize the pathogen from
      contaminated water. Here, we set out to uncover the mechanistic basis of this
      polymer-triggered bacterial behavior. We found that bacteria-polymer aggregates
      undergo rapid autoinduction and achieve quorum sensing at bacterial densities far
      below those required for autoinduction in the absence of polymers. We demonstrate
      this induction of quorum sensing is due both to a rapid formation of autoinducer
      gradients and local enhancement of autoinducer concentrations within bacterial
      clusters as well as the stimulation of CAI-1 and AI-2 production by aggregated
      bacteria. We further found that polymers cause an induction of the biofilm
      specific regulator VpsR and the biofilm structural protein RbmA, bypassing the
      usual suppression of biofilm during autoinduction. Overall, this study highlights
      that synthetic materials can be used to cross-wire natural bacterial responses to
      achieve a combination of phenotypes with potentially useful applications.

PMID- 30204413
TI  - Well-Defined Mo2C Nanoparticles Embedded in Porous N-Doped Carbon Matrix for
      Highly Efficient Electrocatalytic Hydrogen Evolution.
AB  - On the design of efficient and affordable electrocatalysts for water reduction
      half reaction, this paper fabricates molybdenum carbide nanoparticles uniformly
      loaded in highly porous N-doped carbon matrix derived from polyaniline-molybdate
      monolith with the use of graphitic carbon nitride (g-C3N4) as template. The
      obtained molybdenum carbide-carbon hybrid catalysts (MoC@NCS) exhibit
      extraordinarily electrochemical hydrogen evolution activity with a small
      overpotential of 89 and 81 mV to deliver a current density of 10 mA cm-2 in
      alkaline (1.0 M KOH) and acidic (0.5 M H2SO4) medium, respectively, even
      comparable to noble-metal Pt/C benchmark. Specially, MoC@NCS also shows excellent
      long-term durability in alkaline or acidic electrolyte. Furthermore, the obtained
      carbon matrix (NCS) featuring high content of N dopants and hierarchically porous
      architecture exhibits high catalytic efficiency for oxygen evolution reaction in
      alkaline electrolyte. For a further step, the obtained NCS coupled with the
      MoC@NCS, working as anodic and cathodic electrodes, in a two-electrode alkaline
      electrolyzer for overall water splitting, which can obtain a current density of
      10 mA cm-2 at 1.69 V, along with robust operation durability. The synergistic
      effect of the porous carbon matrix of high nitrogen content and the molybdenum
      carbide nanoparticles of uniform distribution, together with hierarchically
      porous structure, should be responsible for the outstanding electrocatalytic HER
      performance. This work presents an easy and cost-effective strategy to prepare
      molybdenum-based materials with controlled size for electrocatalytic hydrogen
      evolution.

PMID- 30204412
TI  - Label-Free Detection of Tear Biomarkers Using Hydrogel-Coated Gold Nanoshells in
      a Localized Surface Plasmon Resonance-Based Biosensor.
AB  - The dependence of the localized surface plasmon resonance (LSPR) of noble-metal
      nanomaterials on refractive index makes LSPR a useful, label-free signal
      transduction strategy for biosensing. In particular, by decorating gold
      nanomaterials with molecular recognition agents, analytes of interest can be
      trapped near the surface, resulting in an increased refractive index surrounding
      the nanomaterial, and, consequently, a red shift in the LSPR wavelength. Ionic
      poly( N-isopropylacrylamide- co-methacrylic acid) (PNM) hydrogels were used as
      protein receptors because PNM nanogels exhibit a large increase in refractive
      index upon protein binding. Specifically, PNM hydrogels were synthesized on the
      surface of silica gold nanoshells (AuNSs). This composite material (AuNS@PNM) was
      used to detect changes in the concentration of two protein biomarkers of chronic
      dry eye: lysozyme and lactoferrin. Both of these proteins have high isoelectric
      points, resulting in electrostatic attraction between the negatively charged PNM
      hydrogels and positively charged proteins. Upon binding lysozyme or lactoferrin,
      AuNS@PNM exhibits large, concentration-dependent red shifts in LSPR wavelength,
      which enabled the detection of clinically relevant concentration changes of both
      biomarkers in human tears. The LSPR-based biosensor described herein has
      potential utility as an affordable screening tool for chronic dry eye and
      associated conditions.

PMID- 30204414
TI  - Gold Nanoparticle and Hydrophobic Nanodiamond Based Synergistic System: A Way to
      Overcome Skin Barrier Function.
AB  - Gold nanoparticles (AuNP) have attracted ample attention as a transdermal (TND)
      drug delivery platform for improving the skin permeability of drug molecules.
      Herein a novel TND device formed from AuNP and oleylamine functionalized
      nanodiamond (AuD) has been developed successfully for the TND delivery of
      Ketoprofen (KP), a model drug. Poly(vinyl alcohol)/Polybutyl methacrylate
      (PVA/PBMA) film has been selected as the matrix of the TND device, as they
      furnish excellent skin adhesion properties. The PVA/PBMA membranes loaded with
      different concentrations of AuD have been characterized in terms of surface
      morphology, thermomechanical properties, water vapor permeability (WVP), optical
      transmittance, cosmetic attractiveness, skin adhesion behavior, and drug
      encapsulation efficiency (DEE). The matrix loaded with 3.0% AuD displayed
      enhanced thermomechanical and DEE due to the uniform distribution of nanofillers
      in the membrane. The in vitro skin permeation test proved that a higher amount of
      KP was delivered by AuD incorporated films, suggesting improved TND behavior. The
      synergistic management of AuNP and nanodiamonds (ND) has caused the enhanced skin
      permeation behavior of the device. The obtained results revealed that AuD may be
      employed as an effective carrier to substitute NDs for TND delivery.
      Additionally, while investigating the storage stability of the device we observed
      that the membrane kept at low temperature presented stability over time. More
      importantly, the results from cell viability assay and environmental fitness test
      revealed that the AuD based TND system is a high security device, as it is
      noncytotoxic and microbe-resistant. The developed device provides a novel and
      handy approach to the TND delivery of drug molecules.

PMID- 30204416
TI  - Delving into the Polar Lipidome by Optimized Chromatographic Separation, High
      Resolution Mass Spectrometry, and Comprehensive Identification with Lipostar:
      Microalgae as Case Study.
AB  - The work describes the chromatographic separation optimization of polar lipids on
      Kinetex-EVO, particularly focusing on sulfolipids in spirulina microalgae (
      Arthrospira platensis). Gradient shape and mobile-phase modifiers (pH and buffer)
      were tested on lipid standards. Different conditions were evaluated, and
      resolution, peak capacity, and peak shape were calculated both in negative mode,
      for sulfolipids and phospholipids, and in positive mode, for glycolipids. A high
      confidence lipid identification strategy was also applied. In collaboration with
      software creators and developers, Lipostar was implemented to improve the
      identification of phosphoglycerolipids and to allow the identification of
      glycosylmonoradyl- and glycosyldiradyl-glycerols classes, the last being the main
      focus of this work. By this approach, an untargeted screening also for searching
      lipids not yet reported in the literature could be accomplished. The optimized
      chromatographic conditions and database search were tested for lipid
      identification first on the standard mixture, then on the polar lipid extract of
      spirulina microalgae, for which 205 lipids were identified.

PMID- 30204415
TI  - Differential Substrate Recognition by Maltose Binding Proteins Influenced by
      Structure and Dynamics.
AB  - The genome of the hyperthermophile Thermotoga maritima contains three isoforms of
      maltose binding protein (MBP) that are high-affinity receptors for di-, tri-, and
      tetrasaccharides. Two of these proteins (tmMBP1 and tmMBP2) share significant
      sequence identity, approximately 90%, while the third (tmMBP3) shares less than
      40% identity. MBP from Escherichia coli (ecMBP) shares 35% sequence identity with
      the tmMBPs. This subset of MBP isoforms offers an interesting opportunity to
      investigate the mechanisms underlying the evolution of substrate specificity and
      affinity profiles in a genome where redundant MBP genes are present. In this
      study, the X-ray crystal structures of tmMBP1, tmMBP2, and tmMBP3 are reported in
      the absence and presence of oligosaccharides. tmMBP1 and tmMBP2 have binding
      pockets that are larger than that of tmMBP3, enabling them to bind to larger
      substrates, while tmMBP1 and tmMBP2 also undergo substrate-induced hinge bending
      motions (~52 degrees ) that are larger than that of tmMBP3 (~35 degrees ). Small
      angle X-ray scattering was used to compare protein behavior in solution, and
      computer simulations provided insights into dynamics of these proteins. Comparing
      quantitative protein-substrate interactions and dynamical properties of tmMBPs
      with those of the promiscuous ecMBP and disaccharide selective Thermococcus
      litoralis MBP provides insights into the features that enable selective binding.
      Collectively, the results provide insights into how the structure and dynamics of
      tmMBP homologues enable them to differentiate between a myriad of chemical
      entities while maintaining their common fold.

PMID- 30204417
TI  - Reversible Detection and Quantification of Hydrogen Sulfide by Fluorescence Using
      the Hemoglobin I from Lucina pectinata.
AB  - A new detection system for the endogenous gaseous transmitter and environmental
      pollutant hydrogen sulfide is presented. It is based on the modulation of the
      fluorescence spectrum of a coumarin dye by the absorption spectrum of the
      recombinant hemoglobin I from clam Lucina pectinata upon coordination of the
      analyte. While we establish that the reported affinity of rHbI for H2S has been
      overestimated, the association of the protein with an appropriate fluorophore
      allows fast, easy, and reversible detection and quantification of hydrogen
      sulfide in buffer as well as biological fluids such as human plasma, with a
      quantification limit around 200 nM at pH 7.4.

PMID- 30204418
TI  - Targeted LC-MS/MS Proteomics-Based Strategy To Characterize in Vitro Models Used
      in Drug Metabolism and Transport Studies.
AB  - Subcellular fractionation of tissue homogenate provides enriched in vitro models
      (e.g., microsomes, cytosol, or membranes), which are routinely used in the drug
      metabolism or transporter activity and protein abundance studies. However, batch
      to-batch or interlaboratory variability in the recovery, enrichment, and purity
      of the subcellular fractions can affect performance of in vitro models leading to
      inaccurate in vitro to in vivo extrapolation (IVIVE) of drug clearance. To
      evaluate the quality of subcellular fractions, we developed a simple, targeted,
      and sensitive LC-MS/MS proteomics-based strategy, which relies on determination
      of protein markers of various cellular organelles, i.e., plasma membrane,
      cytosol, nuclei, mitochondria, endoplasmic reticulum (ER), lysosomes,
      peroxisomes, cytoskeleton, and exosomes. Application of the quantitative
      proteomics method confirmed a significant effect of processing variables (i.e.,
      homogenization method and centrifugation speed) on the recovery, enrichment, and
      purity of isolated proteins in microsomes and cytosol. Particularly, markers of
      endoplasmic reticulum lumen and mitochondrial lumen were enriched in the
      cytosolic fractions as a result of their release during homogenization.
      Similarly, the relative recovery and composition of the total membrane fraction
      isolated from cell vs tissue samples was quantitatively different and should be
      considered in IVIVE. Further, analysis of exosomes isolated from sandwich
      cultured hepatocyte media showed the effect of culture duration on compositions
      of purified exosomes. Therefore, the quantitative proteomics-based strategy
      developed here can be applied for efficient and simultaneous determination of
      multiple protein markers of various cellular organelles when compared to antibody
      or activity-based assays and can be used for quality control of subcellular
      fractionation procedures including in vitro model development for drug metabolism
      and transport studies.

PMID- 30204419
TI  - Influence of Nano- and Microplastic Particles on the Transport and Deposition
      Behaviors of Bacteria in Quartz Sand.
AB  - Plastic particles are widely present in the natural environment and are highly
      likely to interact with bacteria (the ubiquitous microbes in the natural
      environment), which might affect the transport and deposition of bacteria in
      porous media. In this study, the significance of plastic particles from nanoscale
      to micrometer-scale (0.02-2 MUm) on the transport and deposition behaviors of
      bacteria ( Escherichia coli) in quartz sand was examined under environmentally
      relevant conditions in both NaCl and CaCl2 solutions at pH 6. The results showed
      that the presence of different-sized plastic particles did not affect bacterial
      transport behaviors at low ionic strength (10 mM NaCl and 1 mM CaCl2), whereas,
      at high ionic strength conditions (50 mM NaCl and 5 mM in CaCl2), plastic
      particles increased bacterial transport in quartz sand. At low ionic strength
      conditions, the mobility of both plastic particles and bacteria was high, which
      might drive the negligible effects of plastic particles on bacterial transport
      behaviors. The mechanisms driving the enhanced cell transport at high ionic
      strength were different for different-sized plastic particles. Specifically, for
      0.02 MUm nanoplastic particles, the adsorption of plastic particles onto cell
      surfaces and the repel effect induced by suspended plastic particles contributed
      to the increased cell transport. As for 0.2 MUm microplastics (MPs), the
      suspended plastic particles induced  repel effect contributed to the increased
      cell transport, whereas, for 2 MUm MPs, the competition deposition sites by the
      plastic particles were the contributor to the increased cell transport.

PMID- 30204420
TI  - Ionic Polypeptide Polymers with Unusual beta-Sheet Stability.
AB  - Incorporating charged amino acid side chains in polypeptide polymer backbones to
      improve solubility usually leads to reduced secondary structuring. Here we show
      that highly water soluble (>15 mg.mL-1) beta-sheets can be obtained via
      nucleotide monophosphate grafting onto simple poly(gamma-propargyl- L-glutamate)
      backbone. This synthetic methodology has been applied to the synthesis of
      thymidine-based nucleopolypeptides presenting stable beta-sheet conformation in
      aqueous solutions with pH values comprised between 4 and 8. These polymeric
      analogues of nucleoproteins exhibited selective interaction with simple DNA
      sequences displaying adenine.

PMID- 30204421
TI  - Mechanism of Zr Incorporation in the Course of Hydrothermal Synthesis of Zeolite
      BEA.
AB  - The mechanism of Zr-BEA hydrothermal synthesis in fluoride media has been
      investigated through the detailed characterization of samples obtained at
      different synthesis times by XRD, XRF, TGA, multinuclear solid-state NMR, FTIR,
      SEM, TEM with EDS, XAS, and nitrogen sorption. The synthetic procedure involved
      hydrothermal crystallization of the gel with the following composition:
      1SiO2:0.54TEAOH:0.54HF:0.005ZrO2:5.6H2O. The formation of open and closed Lewis
      acid sites was monitored by FTIR spectroscopy of adsorbed CO, while coordination
      of Zr was studied by XAS. The results show that the formation of Zr-BEA proceeds
      by two steps. In the first step, pure silica BEA is crystallized via a solid
      solid hydrogel rearrangement mechanism. Zirconium species are occluded in Si-BEA
      crystals in the form of Zr-rich silicate particles. These particles do not
      provide for any appreciable Lewis acidity. In the second step, Zr incorporation
      into T positions of the zeolite structure takes place, leading to the formation
      of closed Zr sites, which are partially converted into open sites at longer
      synthesis times. It is demonstrated that the content of open and closed sites can
      be tuned by variation of the synthesis time.

PMID- 30204422
TI  - Influence of Temperature-Driven Polymorphism and Disorder on Ionic Conductivity
      in Li6Zn(P2O7)2.
AB  - Ionic conductivity in a compound is rooted in a delicate interplay between its
      crystal structure and its structural defects (vacancies, interstitials, etc.).
      Hence, understanding this interplay is of utmost importance to design new solid
      state electrolytes. To shed some light on the above query, we investigated the
      rich crystal chemistry of Li6Zn(P2O7)2. This compound undergoes multiple
      structural transitions under the influence of temperature, which increases the
      conductivity by several orders and lowers the activation energy. We explained
      this jump in conductivity by the increased disorder associated with cation
      mixing. Our structural exploration indicates that both the room-temperature alpha
      polymorph and the high-temperature zeta-polymorph crystallize in a C2/ c space
      group but with a much smaller unit cell volume for the latter. While their
      structural framework based on P2O74- is similar, the zeta-polymorph presents a
      fully disordered Li/Zn sublattice, while it is fully ordered for the alpha
      polymorph. Furthermore, the bond valence energy landscape calculations show that
      in the alpha-polymorph, the Li+ conduction is two-dimensional, whereas because of
      Li+/Zn2+ site mixing, Li+ can hop three-dimensionally in the zeta-polymorph.

PMID- 30204423
TI  - Phosphine-Catalyzed Asymmetric Organic Reactions.
AB  - Asymmetric phosphine catalysis showcasing remarkable progress over the past two
      decades has emerged as a key synthetic platform for the creation of molecular
      frameworks encountered in medicinal chemistry and materials science. Different
      types of novel chiral phosphine catalysts have been developed and employed in
      cornucopias of organic transformations, such as annulation, addition, Morita
      Baylis-Hillman, and Rauhut-Currier reactions, among others. This review
      summarizes all of the literature examples from late 1990s to the end of 2017,
      alongside their mechanistic insights whenever possible, with a very aim to
      trigger more intensive research in the future to render asymmetric phosphine
      catalysis one of the most common and reliable tools to organic chemists.

PMID- 30204424
TI  - Design and Mechanisms of Asymmetric Supercapacitors.
AB  - Ongoing technological advances in diverse fields including portable electronics,
      transportation, and green energy are often hindered by the insufficient
      capability of energy-storage devices. By taking advantage of two different
      electrode materials, asymmetric supercapacitors can extend their operating
      voltage window beyond the thermodynamic decomposition voltage of electrolytes
      while enabling a solution to the energy storage limitations of symmetric
      supercapacitors. This review provides comprehensive knowledge to this field. We
      first look at the essential energy-storage mechanisms and performance evaluation
      criteria for asymmetric supercapacitors to understand the wide-ranging research
      conducted in this area. Then we move to the recent progress made for the design
      and fabrication of electrode materials and the overall structure of asymmetric
      supercapacitors in different categories. We also highlight several key scientific
      challenges and present our perspectives on enhancing the electrochemical
      performance of future asymmetric supercapacitors.

PMID- 30204425
TI  - Improved Chemical-Genetic Fluorescent Markers for Live Cell Microscopy.
AB  - Inducible chemical-genetic fluorescent markers are promising tools for live cell
      imaging requiring high spatiotemporal resolution and low background fluorescence.
      The fluorescence-activating and absorption shifting tag (FAST) was recently
      developed to form fluorescent molecular complexes with a family of small,
      synthetic fluorogenic chromophores (so-called fluorogens). Here, we use rational
      design to modify the binding pocket of the protein and screen for improved
      fluorescence performances with four different fluorogens. The introduction of a
      single mutation results in improvements in both quantum yield and dissociation
      constant with nearly all fluorogens tested. Our improved FAST (iFAST) allowed the
      generation of a tandem iFAST (td-iFAST) that forms green and red fluorescent
      reporters 1.6-fold and 2-fold brighter than EGFP and mCherry, respectively, while
      having a comparable size.

PMID- 30204426
TI  - The H2O2-Resistant Fe-S Redox Switch MitoNEET Acts as a pH Sensor To Repair
      Stress-Damaged Fe-S Protein.
AB  - Human mitoNEET (mNT) is the first identified Fe-S protein of the mammalian outer
      mitochondrial membrane. Recently, we demonstrated the involvement of mNT in a
      specific cytosolic pathway dedicated to the reactivation of oxidatively damaged
      cytosolic aconitase by cluster transfer. In vitro studies using apo-ferredoxin
      (FDX) reveal that mNT uses an Fe-based redox switch mechanism to regulate the
      transfer of its cluster. Using the "gold standard" cluster recipient protein,
      FDX, we show that this transfer is direct and that only one of the two mNT
      clusters is transferred when the second one is decomposed. Combining
      complementary biophysical and biochemical approaches, we show that pH affects
      both the sensitivity of the cluster to O2 and dimer stability. Around
      physiological cytosolic pH, the ability of mNT to transfer its cluster is tightly
      regulated by the pH. Finally, mNT is extremely resistant to H2O2 compared to ISCU
      and SufB, two other Fe-S cluster transfer proteins, which is consistent with its
      involvement in a repair pathway of stress-damaged Fe-S proteins. Taken together,
      our results suggest that the ability of mNT to transfer its cluster to recipient
      proteins is not only controlled by the redox state of its cluster but also
      tightly modulated by the pH of the cytosol. We propose that when
      pathophysiological conditions such as cancer and neurodegenerative diseases
      dysregulate cellular pH homeostasis, this pH-dependent regulation of mNT is lost,
      as is the regulation of cellular pathways under the control of mNT.

PMID- 30204427
TI  - New Stereoselective Biocatalysts for Carboligation and Retro-Aldol Cleavage
      Reactions Derived from d-Fructose 6-Phosphate Aldolase.
AB  - d-Fructose 6-phosphate aldolase (FSA) catalyzes the asymmetric cross-aldol
      addition of phenylacetaldehyde and hydroxyacetone. We conducted structure-guided
      saturation mutagenesis of noncatalytic active-site residues to produce new FSA
      variants, with the goal of widening the substrate scope of the wild-type enzyme
      toward a range of para- and meta-substituted arylated aldehydes. After a single
      generation of mutagenesis and selection, enzymes with diverse substrate
      selectivity scopes were identified. The kinetic parameters and
      stereoselectivities for a subset of enzyme/substrate combinations were determined
      for the reactions in both the aldol addition and cleavage reaction directions.
      The achieved collection of new aldolase enzymes provides new tools for controlled
      asymmetric synthesis of substituted aldols.

PMID- 30204428
TI  - Detection of Infantile Batten Disease by Tandem Mass Spectrometry Assay of PPT1
      Enzyme Activity in Dried Blood Spots.
AB  - A new tandem mass spectrometry (MS/MS)-based approach for measurement of the
      enzymatic activity of palmitoyl protein thioesterase I (PPT1) in dried blood
      spots (DBS) is presented. Deficiency in this enzyme leads to infantile neuronal
      ceroid lipofuscinosis (INCL, Infantile Batten disease, CLN1). The assay could
      distinguish between 80 healthy newborns and three previously diagnosed INCL
      patients. Unlike the fluorimetric PPT1 assay, the MS/MS assay does not require
      recombinant beta-glucosidase. Furthermore, the assay could be easily combined
      with a TPP1 enzyme assay (for CLN2 disease) and can be potentially multiplexed
      with a large panel of additional lysosomal enzyme assays by MS/MS for newborn
      screening and postscreening analysis.

PMID- 30204429
TI  - Regiochemical Control in the Substitution Reactions of Cyclotriphosphazene
      Derivatives with Secondary Amines.
AB  - The substitution reactions of the monospiro and geminally disubstituted
      cyclotriphosphazene derivatives N3P3Cl4R2 (R2 = OCH2(CF2)2CH2O (1a), SPh (1b),
      OCH2CH2CH2O (1c), NHPh (1d), OCH2CH2CH2NH (1e), NHBut (1f)) with two secondary
      amines (pyrrolidine and dimethylamine) were carried out to investigate geminal or
      non-geminal directing effects in mixed substituent cyclophosphazenes. The
      relative amounts of isomeric products, geminal and non-geminal trans or cis, was
      established quantitatively from the 31P NMR spectra of the reaction mixtures.
      Although secondary amines generally follow a non-geminal pathway in the reactions
      with hexachlorocyclotriphosphazene, in this work, the reactions of two different
      secondary amines with some N3P3Cl4R2 (R2 = OCH2CH2CH2NH, NHPh, NHBut) derivatives
      lead to the formation of geminal products. We have shown that this observation
      depends on the electron-donating properties of the PR2 groups. Isolated compounds
      were analyzed by standard techniques such as elemental analysis, mass
      spectrometry, and 1H and 31P NMR spectroscopy. The structures of compounds for
      which suitable crystals could be obtained were characterized by X-ray
      crystallography.

PMID- 30204430
TI  - Engineered Biosensors from Dimeric Ligand-Binding Domains.
AB  - Biosensors are important components of many synthetic biology and metabolic
      engineering applications. Here, we report a second generation of Saccharomyces
      cerevisiae digoxigenin and progesterone biosensors based on destabilized dimeric
      ligand-binding domains that undergo ligand-induced stabilization. The biosensors,
      comprising one ligand-binding domain monomer fused to a DNA-binding domain and
      another fused to a transcriptional activation domain, activate reporter gene
      expression in response to steroid binding and receptor dimerization. The
      introduction of a destabilizing mutation to the dimer interface increased
      biosensor dynamic range by an order of magnitude. Computational redesign of the
      dimer interface and functional selections were used to create heterodimeric pairs
      with further improved dynamic range. A heterodimeric biosensor built from the
      digoxigenin and progesterone ligand-binding domains functioned as a synthetic
      "AND"-gate, with 20-fold stronger response to the two ligands in combination than
      to either one alone. We also identified mutations that increase the sensitivity
      or selectivity of the biosensors to chemically similar ligands. These dimerizing
      biosensors provide additional flexibility for the construction of logic gates and
      other applications.

PMID- 30204431
TI  - Complex Coacervates between a Lactose-Modified Chitosan and Hyaluronic Acid as
      Radical-Scavenging Drug Carriers.
AB  - Complex coacervation of two oppositely charged polysaccharides, namely a lactose
      modified chitosan (CTL) and hyaluronan (HA), was investigated in this study.
      Coacervates of the two polysaccharides were prepared by drop-by-drop injection of
      HA into CTL. Transmittance and dynamic light scattering (DLS) measurements in
      combination with TEM analyses demonstrated the formation of spheroidal colloids
      in the nano-/microsize range showing good homogeneity. Strikingly, the presence
      of 150 mM supporting NaCl did not hamper the colloid formation. Stability studies
      on selected formulations demonstrated that HA/CTL coacervates were stable up to 3
      weeks at 37  degrees C and behaved as pH-responsive colloids since transition
      from entangled to disentangled chains was attained for a proper pH range. The
      possibility of freeze-drying the coacervates for storage purposes and the ability
      of encapsulating selected payloads were investigated as well, for two values of
      the fraction of the lactitol side-chain substitution (FL). Finally, biological
      tests using human neutrophils were undertaken at acidic pH value (pH = 6.0):
      under such experimental conditions, akin to those frequently occurring in the
      inflammatory microenvironment, coacervates scavenged reactive oxygen species
      (ROS) generated by these cells in basal conditions. Given the well documented
      bioactivity of CTL with respect to chitosan toward cartilage regeneration, these
      findings point to a possible application of HA/CTL-based colloids as scavenging
      and bioactive carriers for the delivery of therapeutic molecules at confined
      inflamed sites such as knee joints.

PMID- 30204432
TI  - Proteoglycan Chemical Diversity Drives Multifunctional Cell Regulation and
      Therapeutics.
AB  - The extracellular matrix (ECM) constitutes a highly dynamic three-dimensional
      structural network comprised of macromolecules, such as
      proteoglycans/glycosaminoglycans (PGs/GAGs), collagens, laminins, fibronectin,
      elastin, other glycoproteins and proteinases. In recent years, the field of PGs
      has expanded rapidly. Due to their high structural complexity and heterogeneity,
      PGs mediate several homeostatic and pathological processes. PGs consist of a
      protein core and one or more covalently attached GAG chains, which provide the
      protein cores with the ability to interact with several proteins. The GAG
      building blocks of PGs significantly influence the chemical and functional
      properties of PGs. The primary goal of this comprehensive review is to summarize
      major achievements and paradigm-shifting discoveries made on the PG/GAG chemistry
      biology axis, focusing on structural variability, structure-function
      relationships, metabolic, molecular, and epigenetic mechanisms underlying their
      synthesis. Recent insights related to exosome biogenesis, degradation, and cell
      signaling, their status as diagnostic tools and potential pharmacological targets
      in diseases as well as current applications in nanotechnology and biotechnology
      are addressed. Moreover, issues related to docking studies, molecular modeling,
      GAG/PG interaction networks, and their integration are discussed.

PMID- 30204433
TI  - DNA Strand Buffers.
AB  - A buffer reaction actively resists changes to the concentration of a chemical
      species. Typically, buffering reactions have only been able to regulate the
      concentration of hydronium (i.e., pH) and other ions. Here, we develop a new
      class of buffers that regulate the concentrations of short sequences of DNA
      (i.e., oligonucleotides). A buffer's behavior is determined by its set point
      concentration, capacity to resist disturbances, and response time after a
      disturbance. We provide simple mathematical formulas for selecting rate constants
      to tune each of these properties and show how to design DNA sequences and
      concentrations to implement the desired rate constants. We demonstrate several
      oligonucleotide buffers that maintain oligonucleotide set point concentrations
      between 10 and 80 nM in the presence of disturbances of 50 to 500 nM, with
      response times of less than 10 min to 1.5 h. Multiple buffers can regulate
      different sequences of DNA in parallel without crosstalk. Oligonucleotide buffers
      could stabilize and restore reactant concentrations in DNA circuits or in self
      assembly processes, allowing such systems to operate reliably for extended
      durations. These buffers might also be coupled to other reactions to buffer
      molecules other than DNA. In general, an oligonucleotide buffer can be viewed as
      a chemical "battery" that maintains the total chemical potential of a buffered
      species in a closed system.

PMID- 30204434
TI  - Tandem Palladium-Catalyzed 6- exo- dig Oxocyclization Coupling of delta
      Acetylenic beta-Ketoesters with Aryl Bromides and Chlorides: Route to Substituted
      Dihydropyrans.
AB  - We report an efficient and functional group-tolerant method for the synthesis of
      substituted dihydropyrans, based on tandem Pd-catalyzed cyclization/coupling of
      delta-acetylenic beta-ketoesters with aryl halides. The reaction proceeds cleanly
      through 6- exo-dig oxocyclizaton mode, delivering products with very good yields
      and complete control of regio- and stereoselectivity. Due to mild conditions, the
      transformation offers exceptional tolerance of functionalities, including NHR,
      formyl, enolizable ketone, free OH and NH2 groups, as well as a range of N
      heterocyclic moieties of potential biological relevance.

PMID- 30204435
TI  - Generating Intrinsically Disordered Protein Conformational Ensembles from a
      Database of Ramachandran Space Pair Residue Probabilities Using a Markov Chain.
AB  - Intrinsically disordered proteins (IDPs), involved in regulatory pathways and
      cell signaling, sample a range of conformations. Constructing structural
      ensembles of IDPs is a difficult task for both experiment and simulation. In this
      work, we produce potential IDP ensembles using an existing database of pair
      residue phi and psi angle probabilities chosen from turn, coil, and bend parts of
      sequences from the Protein Data Bank. For all residue pair types, a k-means-based
      discretization is used to create a set of rotamers and their probabilities in
      this pair Ramachandran space. For a given sequence, a Markov-based probabilistic
      algorithm is used to create Ramachandran space database-Markov ensembles that are
      converted to Cartesian coordinates of the backbone atoms. From these Cartesian
      coordinates and phi and psi dihedral angles of a sequence, various observables:
      the radius of gyration and shape parameters, the distance probability
      distribution that is related to the small-angle X-ray scattering intensity, atom
      atom contact percentages, local structural information, NMR three-bond J
      couplings, CA chemical shifts, and residual dipolar couplings are evaluated. A
      benchmark set of ensembles for 16 residue, regular sequences is constructed and
      used to validate the method and to explore the implications of the database for
      some of the above-mentioned observables. Then, we examine a set of nonapeptides
      of the form EGAAXAASS where X denotes residues of different characters. These
      peptides were studied by NMR, and subsequent molecular dynamics (MD) simulations
      were carried out using various force fields to find which one best agrees with
      the NMR data. Our analysis of these peptides shows that the combination of the
      database and the Markov algorithm yields ensembles that agree very well with the
      NMR and MD results for the above-listed observables. Thus, this database-Markov
      method is a promising method to generate IDP conformational ensembles.

PMID- 30204436
TI  - Electrochemically Driven Water-Oxidation Catalysis Beginning with Six Exemplary
      Cobalt Polyoxometalates: Is It Molecular, Homogeneous Catalysis or Electrode
      Bound, Heterogeneous CoO x Catalysis?
AB  - A series of six exemplary cobalt-polyoxometalate (Co-POM) precatalysts have been
      examined to determine if they are molecular water-oxidation catalysts
      (WOCatalysts) or if, instead, they actually form heterogeneous, electrode-bound
      CoO x as the true WOCatalyst under electrochemically driven water-oxidation
      catalysis (WOCatalysis) conditions. Specifically, WOCatalysis derived from the
      following six Co-POMs has been examined at pH 5.8, 8.0, and 9.0:
      [Co4(H2O)2(PW9O34)2]10- (Co4P2W18), [Co9(H2O)6(OH)3(HPO4)2(PW9O34)3]16-
      (Co9P5W27), [ betabeta-Co4(H2O)2(P2W15O56)2]16- (Co4P4W30), [Co(H2O)PW11O39]5-
      (CoPW11), [alpha1-Co(H2O)P2W17O61]8- (alpha1-CoP2W17), and [alpha2
      Co(H2O)P2W17O61]8- (alpha2-CoP2W17). The amount of Co(II)aq in 500 MUM solutions
      of each Co-POM was measured after 3 h of aging as well as from t = 0 for pH = 5.8
      and 8.0 by MUM sensitive Co(II)aq-induced 31P NMR line broadening and at pH = 9.0
      by cathodic stripping. The amount of detectable Co(II)aq after 3 h for the six Co
      POMs ranges from ~0.25 to ~90% of the total cobalt initially present in the Co
      POM. For 12 out of 18 total Co-POM and different pH cases, the amount Co(II)aq
      detected after 3 h forms heterogeneous CoO x able to account for >=100% of the
      observed WOCatalysis activity. However, under 0.1 M NaPi, pH 5.8 conditions for
      CoPW11 and alpha1-CoP2W17 where ~1.5% and 0.25% Co(II)aq is detectable, the
      measured Co(II)aq cannot account for the observed WOCatalysis. The implication is
      that these two Co-POMs are primarily molecular, Co-POM-based, WOCatalysts under
      electrochemically driven, pH 5.8, phosphate-buffer conditions. Even for the
      single most stable Co-POM, alpha1-CoP2W17, CoO x is still an estimated ~76*
      faster WOCatalyst at pH = 5.8 and an estimated ~740* faster WOCatalyst at pH = 8.

PMID- 30204437
TI  - Elucidating Aggregation Pathways in the Donor-Acceptor Type Molecules p
      DTS(FBTTh2)2 and p-SIDT(FBTTh2)2.
AB  - We investigated the aggregation behavior of the donor-acceptor molecules p
      DTS(FBTTh2)2 (T1) and p-SIDT(FBTTh2)2 (H1) in MTHF solutions. Using optical
      spectroscopy, we found that T1 forms aggregates in solution while H1 aggregates
      only when processed as a thin film, but not in solution. Free energy molecular
      dynamics (MD) simulations based on force fields derived from quantum-mechanical
      density functional theory fully reproduce this difference. Our simulations reveal
      that this difference is not due to the lengthy carbon side chains. Rather, the
      molecular symmetry of T1 allows for an aggregated state in which the central
      donor units are spatially well-separated while a similar configuration is
      sterically impossible for H1. As a consequence, any aggregation of H1 necessarily
      involves aggregation of the central donors which requires, as a first step,
      stripping the central donor of its protective MTHF solvation shell. This
      unfavorable process leads to a significant kinetic hindrance for aggregation and
      explains the strongly differing aggregation behavior of T1/H1 in MTHF despite
      their otherwise similar structures.

PMID- 30204438
TI  - Manganese-Based Contrast Agents for Magnetic Resonance Imaging of Liver Tumors:
      Structure-Activity Relationships and Lead Candidate Evaluation.
AB  - Gd-based MRI contrast agents (GBCAs) have come under intense regulatory scrutiny
      due to concerns of Gd retention and delayed toxicity. Three GBCAs comprising
      acyclic Gd chelates, the class of GBCA most prone to Gd release, are no longer
      marketed in Europe. Of particular concern are the acyclic chelates that remain
      available for liver scans, where there is an unmet diagnostic need and no
      replacement technology. To address this concern, we evaluated our previously
      reported Mn-based MRI contrast agent, Mn-PyC3A, and nine newly synthesized
      derivatives as liver specific MRI contrast agents. Within this focused library
      the transient liver uptake and rate of blood clearance are directly correlated
      with log P. The complex Mn-PyC3A-3-OBn emerged as the lead candidate due to a
      combination of high relaxivity, rapid blood clearance, and avid hepatocellular
      uptake. Mn-PyC3A-3-OBn rendered liver tumors conspicuously hypo-intense in a
      murine model and is wholly eliminated within 24 h of injection.

PMID- 30204439
TI  - Enhancement of the Production of Bioactive Microalgal Metabolites by Ultraviolet
      Radiation (UVA 365 nm).
AB  - Two marine microalgae, Nitzschia closterium and Isochrysis zhangjiangensis,
      treated for 9 days with photosynthetically active radiation (PAR), were subjected
      to 3 days of ultraviolet light band A at 365 nm (UVA365) followed by a 3 day post
      UVA PAR treatment. Compared with the control that only had PAR treatment, UVA365
      treatment significantly ( p < 0.05) increased the amounts of total xanthophylls
      in N. closterium and I. zhangjiangensis by up to 3.53- and 1.23-fold,
      respectively, after 3 days of UVA365 irradiation. In particular, UVA365 treatment
      markedly ( p < 0.05) increased two major bioactive xanthophyll pigments,
      fucoxanthin in N. closterium and diadinoxanthin in I. zhangjiangensis, by up to
      1.97- and 1.52-fold, respectively. UVA365 treatment significantly ( p < 0.05)
      increased the accumulation of another bioactive microalgal metabolite, total
      mycosporine-like amino acids, in N. closterium and I. zhangjiangensis by up to
      1.40- and 1.30-fold, respectively. UVA365 irradiation has potential as an
      efficient approach for enhancing the production of valuable microalgal
      metabolites.

PMID- 30204440
TI  - An Analysis of Different Components of a High-Throughput Screening Library.
AB  - Since many projects at pharmaceutical organizations get their start from a high
      throughput screening (HTS) campaign, improving the quality of the HTS deck can
      improve the likelihood of discovering a high-quality lead molecule that can be
      progressed to a drug candidate. Over the past decade, Janssen has implemented
      several strategies for external compound acquisition to augment the screening
      deck beyond the chemical space and number of molecules synthesized for internal
      projects. In this report, we analyzed the performance of each of those compound
      collections in the screening campaigns performed internally within Janssen during
      the last five years. We classified the screening library into two broad
      categories: Internal and External. The comparison of the performance of these
      sets of libraries was done by considering the primary, confirmation, and dose
      response hit rates. Our analysis revealed that Internal compounds (resulting from
      numerous medicinal chemistry efforts against diverse protein targets) have higher
      average confirmation hit rates than External ones; however, actives from both
      categories show similar probabilities of hitting multiple distinct targets. We
      also investigated the property landscape of both sets of libraries to identify
      the key elements which make a difference in these categories of compounds. From
      this analysis, Janssen aims to understand the descriptor landscape of the
      compounds with the highest hit rates and to use them for improving its future
      acquisition strategies as well as to inform our plating strategy.

PMID- 30204442
TI  - Photoinduced Heterocyclic Ring Opening of Furfural: Distinct Open-Chain Product
      Identification by Ultrafast X-ray Transient Absorption Spectroscopy.
AB  - The ultraviolet-induced photochemistry of five-membered heterocyclic rings often
      involves ring opening as a prominent excited-state relaxation pathway. The
      identification of this particular photoinduced mechanism, however, presents a
      challenge for many experimental methods. We show that femtosecond X-ray transient
      absorption spectroscopy at the carbon K-edge (~284 eV) provides core-to-valence
      spectral fingerprints that enable the unambiguous identification of ring-opened
      isomers of organic heterocycles. The unique differences in the electronic
      structure between a carbon atom bonded to the oxygen in the ring versus a carbon
      atom set free of the oxygen in the ring-opened product are readily apparent in
      the X-ray spectra. Ultrafast ring opening via C-O bond fission occurs within ~350
      fs in 266-nm photoexcited furfural, as evidenced by fingerprint core (carbon 1s)
      electronic transitions into a nonbonding orbital of the open-chain carbene
      intermediate at 283.3 eV. The lack of recovery of the 1spi* ground-state
      depletion in furfural at 286.4 eV indicates that internal conversion to the
      ground state is a minor channel. These experimental results, augmented by recent
      advances in the generation of isolated attosecond pulses at the carbon K-edge,
      will pave the way for probing ring-opened conical intersection dynamics in the
      future.

PMID- 30204441
TI  - Discovery of N-(4-{[5-Fluoro-7-(2-methoxyethoxy)quinazolin-4-yl]amino}phenyl)-2
      [4-(propan-2-yl)-1 H-1,2,3-triazol-1-yl]acetamide (AZD3229), a Potent Pan-KIT
      Mutant Inhibitor for the Treatment of Gastrointestinal Stromal Tumors.
AB  - While the treatment of gastrointestinal stromal tumors (GISTs) has been
      revolutionized by the application of targeted tyrosine kinase inhibitors capable
      of inhibiting KIT-driven proliferation, diverse mutations to this kinase drive
      resistance to established therapies. Here we describe the identification of
      potent pan-KIT mutant kinase inhibitors that can be dosed without being limited
      by the tolerability issues seen with multitargeted agents. This effort focused on
      identification and optimization of an existing kinase scaffold through the use of
      structure-based design. Starting from a series of previously reported
      phenoxyquinazoline and quinoline based inhibitors of the tyrosine kinase
      PDGFRalpha, potency against a diverse panel of mutant KIT driven Ba/F3 cell lines
      was optimized, with a particular focus on reducing activity against a KDR driven
      cell model in order to limit the potential for hypertension commonly seen in
      second and third line GIST therapies. AZD3229 demonstrates potent single digit nM
      growth inhibition across a broad cell panel, with good margin to KDR-driven
      effects. Selectivity over KDR can be rationalized predominantly by the
      interaction of water molecules with the protein and ligand in the active site,
      and its kinome selectivity is similar to the best of the approved GIST agents.
      This compound demonstrates excellent cross-species pharmacokinetics, shows strong
      pharmacodynamic inhibition of target, and is active in several in vivo models of
      GIST.

PMID- 30204443
TI  - Zn2+-Binding to the Voltage-Gated Proton Channel Hv1/VSOP.
AB  - The voltage-gated proton channel (Hv1/VSOP) is inhibited by Zn2+, of which the
      binding site is located in the extracellular region. We utilized attenuated total
      reflection-Fourier transform infrared (ATR-FTIR) spectroscopy to examine the
      coordination structure by monitoring protein structural changes induced by Zn2+
      binding. The Zn2+-induced difference ATR-FTIR spectra of Hv1 showed IR features
      that can be assigned to the histidine C5-N1 and carboxylate-COO- stretches as
      well as amide I changes likely in alpha-helical peptide bonds. Analysis of
      vibrational frequencies indicated that the Zn2+ is coordinated by the anionic
      carboxylate with monodentate mode and by the histidine at N1 (Ntau) position of
      the neutral imidazole form. Combined with quantum chemical calculations, the most
      probable coordination structure was proposed as a tetrahedral geometry with
      ligands of carboxylate and imidazole groups in addition to a water molecule.

PMID- 30204444
TI  - Partial Hydrogenation of Unsaturated Carbonyl Compounds: Toward Ligand-Directed
      Heterogeneous Catalysis.
AB  - In this Perspective, we report on the recent progress in atomistic-level
      understanding of selective partial hydrogenation of alpha,beta-unsaturated
      carbonyl compounds, particularly acrolein, toward unsaturated alcohols over model
      single crystalline and nanostructured Pd catalysts. This reaction was observed to
      proceed with nearly 100% selectivity over Pd(111) but not over supported Pd
      nanoparticles. The origin of the high selectivity was related to formation of a
      dense overlayer of oxopropyl surface species occurring at the early reaction
      stages via partial hydrogenation of the C=C bond in acrolein with only one H
      atom. This oxopropyl overlayer strongly modifies the adsorption and reactive
      properties of Pd(111), turning it 100% selective toward C=O bond hydrogenation.
      The underlying reaction mechanism represents a particular case of ligand-directed
      heterogeneous catalysis, in which the surface adsorbates do not directly
      participate in the catalytic process as the reaction intermediates but strongly
      affect the elementary reaction steps via specific adsorbate-adsorbate
      interactions.

PMID- 30204445
TI  - Enhanced Two-Photon Photochromism in Metasurface Perfect Absorbers.
AB  - Light switchable materials are essential to optoelectronic applications in
      photovoltaics, memories, sensors, and communications. Natural switchable
      materials suffer from weak absorption and slow response times, preventing their
      use in low-power, ultrafast applications. Integrating light switchable materials
      with metasurface perfect absorbers offers an innovative route to achieving
      desirable features for nanophotonic devices, such as directional emission, low
      power and broadband operation, high radiative quantum efficiency, and large
      spontaneous emission rates. Here we show an enhanced two-photon photochromism
      based on a metasurface perfect absorber: film-coupled colloidal silver nanocubes.
      The photochromic molecules, spiropyrans, are sandwiched between the silver
      nanocubes and the gold substrate. With nearly 100% absorption and an accompanying
      large field enhancement in the molecular junction, the transformation of
      spiropyrans to merocyanines is observed under excitation with 792 nm laser light.
      Fluorescence lifetime measurements on the merocyanine form reveal that large
      Purcell enhancement in the film-coupled nanocubes leads to large enhancements of
      the spontaneous emission rate and a high quantum efficiency. An averaged incident
      power as low as 10 MUW is enough to initiate the two-photon isomerization of
      spiropyran in the film-coupled nanocubes, and a power of 100nW is able to excite
      the merocyanines to emit fluorescence. The power consumption is orders of
      magnitude lower than bare spiropyran thin films on silicon and gold, which is
      highly desirable for the writing and reading processes relevant to optical data
      storage. By sweeping the plasmonic resonance of the film-coupled nanocubes,
      wavelength specificity is demonstrated, which opens up new possibilities for
      minimizing the cross talk between adjacent bits in nanophotonic devices.

PMID- 30204446
TI  - Negative Surface Shielded Polymeric Micelles with Colloidal Stability for
      Intracellular Endosomal/Lysosomal Escape.
AB  - The critical process and step in achieving effective antitumor therapies is
      facilitating endosomal escape, which can enhance the intracellular target
      delivery of therapeutics. However, the normally adopted approaches tend to result
      in colloidal instability as a result of the inevitable interactions between the
      resulting positively charged surfaces of micelles and proteins in vivo. Herein,
      negatively charged surface shielded polymeric micelles, consisting of
      polymethylacrylamide derivatives and hydrophilic chitosan ( Mw = 18.8 kDa) linked
      by 3,3'-dithiodipropionic, are constructed. Until the pH decreases to less than
      4.5, the DOX-loaded polymeric micelles (CSO-SS-PDPA/DOX) retain a negative
      surface charge as a result of the abundant amide groups, which could resist
      formation of the protein "corona" as visualized by transmission electron
      microscopy. Robust endosomal escape within tens of minutes due to protonated
      amine groups and specific redox-responsive drug release is visualized by confocal
      microscopy. The superior therapeutic efficacy in both 3D tumor spheroids and MCF
      7 bearing mice further suggested that the prepared CSO-SS-PDPA/DOX is a promising
      approach for maintaining colloidal stability while achieving intracellular
      endosomal/lysosomal escape, which opens new opportunities for drug delivery.

PMID- 30204447
TI  - Tensile Loads on Tethered Actin Filaments Induce Accumulation of Cell Adhesion
      Associated Proteins in Vitro.
AB  - Focal adhesions (FAs) and adherens junctions (AJs), which serve as a mechanical
      interface of cell-matrix and cell-cell interactions, respectively, experience
      tensile force either originating from the deformation of the surrounding tissues
      or generated by the actomyosin machinery in the cell. These mechanical inputs
      cause enlargement of FAs and AJs, while the detailed mechanism for the force
      dependent development of FAs and AJs remain unclear. Both FAs and AJs provide
      sites for tethering of actin filaments and actin polymerization. Here, we develop
      a cell-free system, in which actin filaments are tethered to glass surfaces, and
      show that application of tensile force to the tethered filaments in the cell
      extract induces accumulation of several FA and AJ proteins, associated with
      further accumulation of actin filaments via de novo actin polymerization. Decline
      in the tensile force results in a decrease in the amount of the accumulated
      proteins. These results suggest that the tensile force acting on the tethered
      actin filaments plays a crucial role in the accumulation of FA and AJ proteins.

PMID- 30204448
TI  - Direct Measurements of Carrier Transport in Polycrystalline Methylammonium Lead
      Iodide Perovskite Films with Transient Grating Spectroscopy.
AB  - Hybrid organic-inorganic halide perovskites have been proposed in many
      optoelectronic applications, but critical to their increasing functionality and
      utility is understanding and controlling carrier transport. Here, we use light
      induced transient grating spectroscopy to probe directly carrier transport in
      polycrystalline methylammonium lead iodide perovskite thin films using a weakly
      perturbative and noncontact method. The data reveal intrinsic diffusion
      characteristics of the charge carriers in the material and agree well with a
      simulated model of charge transport in which grain boundaries act as barriers to
      carrier movement.

PMID- 30204449
TI  - Interaction of Folic Acid with Nanocrystalline Apatites and Extension to
      Methotrexate (Antifolate) in View of Anticancer Applications.
AB  - Nanocrystalline apatites mimicking bone mineral represent a versatile platform
      for biomedical applications thanks to their similarity to bone apatite and the
      possibility to (multi)functionalize them so as to provide "a la carte"
      properties. One relevant domain is in particular oncology, where drug-loaded
      biomaterials and engineered nanosystems may be used for diagnosis, therapy, or
      both. In a previous contribution, we investigated the adsorption of doxorubicin
      onto two nanocrystalline apatite substrates, denoted HA and FeHA
      (superparamagnetic apatite doped with iron ions), and explored these drug-loaded
      systems against tumor cells. To widen their applicability in the oncology field,
      here we examine the interaction between the same two substrates and two other
      molecules: folic acid (FA), often used as cell targeting agent, and the
      anticancer drug methotrexate (MTX), an antifolate analogue. In a first stage, we
      investigated the adsorptive behavior of FA (or MTX) on both substrates,
      evidencing their specificities. At low concentration, typically under 100 mmol/L,
      adsorption onto HA was best described using the Sips isotherm model, while the
      formation of a calcium folate secondary salt was evidenced at high concentration
      by Raman spectroscopy. Adsorption onto FeHA was instead fitted to the Langmuir
      model. A larger adsorptive affinity was found for the FeHA substrate compared to
      HA; accordingly, a faster release was noticed from HA. In vitro tests carried out
      on human osteosarcoma cell line (SAOS-2) allowed us to evaluate the potential of
      these compounds in oncology. Finally, in vivo (subcutaneous) implantations in the
      mouse were run to ascertain the biocompatibility of the two substrates. These
      results should allow a better understanding of the interactions between FA/MTX
      and bioinspired nanocrystalline apatites in view of applications in the field of
      cancer.

PMID- 30204451
TI  - Preparation of Structurally Diverse Compounds from the Natural Product Lycorine.
AB  - The synthesis of a 52-member compound collection from the natural product
      lycorine is reported, highlighted by divergent cross-coupling and substitution
      strategies and an unusual ring rearrangement induced by reaction with aryne
      intermediates.

PMID- 30204450
TI  - Asymmetrical Electrowetting on Dielectrics Induced by Charge Transfer through an
      Oil/Water Interface.
AB  - Electrowetting on dielectrics is a fascinating as well as a precise way in
      microfluid manipulation. As one of the controversial conclusions, charge trapping
      on the dielectric surface might be one of the causes which induces water contact
      angle saturation and forms one of the significant issues that bear on the
      applications of electrowetting on dielectrics. Recently, it was demonstrated that
      the contact angle saturation can be significantly reduced by employing an oil
      lubrication layer on the hydrophobic surface. In this work, we have investigated
      the influence of effects of an oil layer on the electrowetting behavior by
      dissolving a nonpolar oil-soluble dye in the oil phase. We monitored the contact
      angle of water drops with varying pH on an oil-lubricated hydrophobic insulator.
      Interestingly, we found asymmetry in the electrowetting curve. Several analysis
      methods were proceeded trying to explain this asymmetric electrowetting
      phenomenon. First and foremost, the electrochemical properties of dye were
      investigated by cyclic voltammetry which demonstrates that oxidation-reduction
      reactions of the dye can indeed happen on the electrode and one irreversible peak
      was found which indicated that the dye molecule might decompose at a higher
      voltage. Second, thin-layer cyclic voltammetry confirmed ions can transgress the
      oil/water interface. Also, the conductivity of the oil phase increases with the
      dissolved dye concentration, which indicates that charges can be transported in
      the oil phase. Finally, to further understand the transfer mechanism, the
      transient current of dye-doped oil was measured, which indicates that the
      formation of inverse micelles in the oil phase at high voltage could be one of
      the charge carriers. We demonstrated the oil-property-dependent asymmetry
      phenomenon of electrowetting and its association with charge transfer through the
      oil/water interface for the first time.

PMID- 30204452
TI  - Zwitterionic Reduction-Activated Supramolecular Prodrug Nanocarriers for
      Photodynamic Ablation of Cancer Cells.
AB  - An adamantane-containing zwitterionic copolymer poly(2-(methacryloyloxy)ethyl
      phosphorylcholine)- co-poly(2-(methacryloyloxy)ethyl adamantane-1-carboxylate)
      (poly(MPC- co-MAda)) was prepared by reversible addition-fragmentation chain
      transfer (RAFT) polymerization. The hydrophobic photosensitizer chlorin e6 (Ce6)
      was conjugated to beta-cyclodextrin (beta-CD) by glutathione (GSH)-sensitive
      disulfide bonds. The Ce6 conjugated supramolecular prodrug nanocarriers were
      fabricated due to the host-guest interaction between adamantane and beta-CD,
      which was confirmed by dynamic light scattering (DLS) and transmission electron
      microscopy (TEM). The Ce6 conjugated prodrug nanocarriers showed reduction
      responsive release of Ce6, which could result in the activation of Ce6. The
      generation of cytotoxic reactive oxygen species (ROS) was significantly enhanced
      due to the activation of Ce6. In additiona, the Ce6 conjugated prodrug
      nanocarriers could effectively inhibit the proliferation of cancer cells upon
      light irradiation.

PMID- 30204453
TI  - Ru(II)-Catalyzed Synthesis of Substituted Furans and Their Conversion to
      Butenolides.
AB  - The synthesis of densely functionalized trisubstituted and tetrasubstituted
      furans via a novel Ru(II)-catalyzed intramolecular cyclization of vinyl
      diazoesters is reported. The synthetic utility of these furans is further
      demonstrated through a simple acid-mediated reaction to access highly substituted
      Deltaalpha,beta-butenolides.

PMID- 30204454
TI  - Sophalines E-I, Five Quinolizidine-Based Alkaloids with Antiviral Activities
      against the Hepatitis B Virus from the Seeds of Sophora alopecuroides.
AB  - Five novel quinolizidine-based alkaloids (1-5) were obtained from the seeds of
      Sophora alopecuroides L. Compounds 1 and 2 are the first examples of sparteine
      indolizine and matrine-indolizine alkaloids, respectively, whereas 3 and 4 are
      epimeric normatrine-julolidine alkaloids with unusual skeletons. The structures
      of these compounds were determined by spectroscopic methods, single-crystal X-ray
      diffraction, and electronic circular dichroism analyses. Hypothetical
      biosynthetic pathways of 1-5 were proposed. Compound 2 exhibited significant
      antiviral activity against the hepatitis B virus.

PMID- 30204455
TI  - Benign Synthesis of Thiazolo-androstenone Derivatives as Potent Anticancer
      Agents.
AB  - An unprecedented reaction of thiourea derivatives with 6beta-bromoandrostenedione
      has been discovered for the formation of aminothiazolo-androstenones via a
      simple, safer, cascade protocol that enables the syntheses of novel molecules by
      using readily available reagents. The reaction mechanism of product formation has
      been rationalized by density functional theory calculations. This benign
      methodology accentuates a domino protocol deploying a renewable solvent, ethanol,
      while generating novel compounds that display potent growth inhibitory effects in
      in vitro studies for several cancer cell lines at submicromolar concentrations.

PMID- 30204456
TI  - Mechanical Softening of a Small Ubiquitin-Related Modifier Protein Due to
      Temperature Induced Flexibility at the Core.
AB  - Despite the growing interest in the thermal softening of proteins, the
      mechanistic details of it are far from understood. beta-Grasp proteins have
      globular shape with compact structure and they are mechanically resilient. The
      beta-clamp or mechanical clamp in them formed by the interactions between the
      terminal beta-strands is generally associated with the protein mechanical
      resistance. Although previous studies showed that temperature can perturb the
      protein mechanical stability, the structural changes leading to the lowered
      mechanical resistance are not known. Here, we investigated the temperature
      dependent mechanical stability of small ubiquitin-related modifier 2 (SUMO2)
      using single-molecule force spectroscopy (SMFS) and the corresponding
      conformational changes using ensemble experiments. SMFS studies on the
      polyprotein of SUMO2 estimate a decrease in the spring constant of the protein
      from 4.50 to 1.35 N/m upon increasing the temperature from 5 to 45  degrees C.
      Interestingly, near-UV circular dichroism spectroscopy reveals a decrease in
      tertiary structure content while the overall secondary structure of the protein
      remains unchanged. Steady-state fluorescence and quenching studies on SUMO2 with
      a tryptophan mutation at the core (F60W) show that the nonpolar environment of
      the tryptophan is unchanged and the protein core is inaccessible to the bulk
      solvent, in the same temperature range. We attribute the thermal softening
      observed in atomic force microscopy (AFM) experiments to the reduction in
      tertiary structure of SUMO2. Our results provide evidence for the importance of
      the intramolecular interactions at the protein core along with the beta-clamp or
      mechanical clamp in providing the mechanical resistance as well as in modulating
      the protein stiffness.

PMID- 30204457
TI  - Cardiovascular regulation and body temperature: evidence from a nap vs. sleep
      deprivation randomized controlled trial.
AB  - In this study we set out to understand is sleep fragmentation affects the
      cardiovascular regulation and circadian variability of core body temperature more
      or less than sleep deprivation. 50 healthy men (age 29.0+/-3.1 years; BMI 24.3+/
      2.1 kg/m(2)) participated in a 3-day study that included one adaptative night and
      one experimental night involving randomization to: sleep deprivation (SD) and
      sleep fragmentation (SF). The evaluation included hemodynamic parameters,
      measures of the spectral analysis of heart rate and blood pressure variability,
      and the sensitivity of arterial baroreflex function. Core body temperature (CBT)
      was measured with a telemetric system. SF affects heart rate (61.9+/-5.6 vs
      56.2+/-7.6, p<0.01) and stroke index (52.7+/-11.1 vs. 59.8+/-12.2, p<0.05) with
      significant changes in the activity of the ANS (LF-sBP: 6.0+/-5.3 vs. 3.4+/-3.7,
      p<0.05; HF-sBP: 1.8+/-1.8 vs 1.0+/-0.7, p<0.05; LF-dBP: 5.9+/-4.7 vs. 3.5+/-3.2,
      p<0.05) more than SD. Post-hoc analysis revealed that after SD mean value of CBT
      from 21:30 to 06:30 was significantly higher compared to normal night's sleep and
      SF. In healthy men SF affects the hemodynamic and autonomic changes more than SD.
      Sympathetic overactivity is the proposed underlying mechanism.

PMID- 30204458
TI  - Serum HMGB1 levels and its association with endothelial dysfunction in patients
      with polycystic ovary syndrome.
AB  - High-mobility group box1(HMGB1) is newly discovered protein, which play a crucial
      role in the pathogenesis of systemic inflammation Recent studies showed that
      HMGB1 is one of the important pathophysiological mechanisms in the occurrence and
      development of atherosclerosis. The purpose of the present study was to
      investigate the relationship between serum HMGB1 levels and endothelial function
      in patients with polycystic ovary syndrome (PCOS). 80 newly diagnosed patients
      with PCOS and 80 normal women of similar age were selected. Metformin treatment
      (1500 mg/d) was initiated in all patients for a period of consecutive 3 months.
      Serum HMGB1 levels were measured by ELISA. High resolution ultrasound was used to
      measure the brachial artery diameter at rest, after reactive hyperemia (flow
      mediated arterial dilation, FMD) and after sublingual glyceryltrinitrate. Serum
      HMGB1 levels in PCOS were 24.87+/-14.93 ng/ml, which were significantly higher
      than that in controls (8.82+/-3.55 ng/ml) (p<0.01). After 3 months treatment,
      serum HMGB1 levels decreased significantly (p < 0.05).By dividing the
      distribution of HMGB1 levels into quartiles, serum HMGB1 levels were increased
      gradually with the increase of testosterone levels (p < 0.05),whereas the FMD
      levels decreased (p < 0.05). Multiple stepwise linear regression analysis showed
      that FMD (estimated coefficient (beta)=-0.69, p=0.005), testosterone (beta=0.31,
      p =0.045), TBARS (beta=0.69, p=0.012) and hs-CRP levels (beta=0.68, p=0.001) were
      significantly associated with HMGB1.The absolute changes in HMGB1 showed a
      positive correlation with the changes in testosterone (p < 0.05) and negative
      correlation with the changes in FMD (p < 0.05) in patients with PCOS during the
      course of metformin therapy. Serum HMGB1 levels are correlated with endothelil
      dysfunction in patients with PCOS Our study suggests that HMGB1 may contribute to
      the early stage of atherosclerosis in patients with PCOS.

PMID- 30204459
TI  - Natural remodeling of the distal anastomosis of an above-knee femoropopliteal
      bypass depicted by CT angiography of lower limbs improves geometry of the
      reconstruction.
AB  - The geometry of a distal anastomosis of a femoropopliteal bypass influences local
      hemodynamics and formation of intimal hyperplasia. We hypothesized that the
      distal anastomosis of an above-knee femoropopliteal bypass undergoes remodeling
      that results in displacement of the original course of the popliteal artery and
      change in the anastomosis angle. We identified 43 CT angiography examination with
      proximal femoropopliteal bypass and either a preserved contralateral popliteal
      artery or previous CTA before construction of the bypass for comparison. In these
      examinations, we measured the displacement distance and angle at the level of the
      distal anastomosis and compared these measurements with clinical and imaging
      data. The displacement distance was 8.8+/-4.9 mm (P<0.0001) and the displacement
      angle was -1 degrees  (IQR=44 degrees ). The angle between the inflow and outflow
      artery was 153+/-16 degrees  (P<0.0001). There was a negative association between
      the displacement angle and the angle between the bypass and the outflow artery
      (r=-0.318, P=0.037). Patients with reversed venous grafts had a greater
      displacement of the anastomosis (14.7 mm+/-3.0 mm) than patients with prosthetic
      grafts (8.0+/-4.5 mm, P=0.0011). We conclude that construction of a distal
      anastomosis of proximal femoropopliteal bypass results in displacement of the
      original course of the popliteal artery towards the bypass and this effect is
      more pronounced in reversed venous grafts.

PMID- 30204460
TI  - Markers of oxidative stress and antioxidant status in the plasma, urine and
      saliva of healthy mice.
AB  - Oxidative stress markers are usually measured in plasma, a stable environment for
      biomarkers. Blood collection is invasive, but the use of alternative biofluids is
      limited, due to high variability. In this study, we aimed to establish reference
      values for oxidative stress markers in plasma, urine and saliva of adult, healthy
      mice and to identify some sources of variability. Samples were obtained from 41
      female and 37 male adult, healthy mice of the CD-1 strain, aged 95-480 days,
      weighing 21-55 grams. Reference ranges of TBARS (thiobarbituric acid reactive
      substances), AOPP (advanced oxidation protein products), fructosamine, GSH/GSSG
      (reduced and oxidised glutathione) ratio, TAC (total antioxidant capacity), and
      FRAP (ferric reducing antioxidant power) were measured in plasma and urine, and
      TBARS, GSH/GSSG ratio, TAC and FRAP in saliva, using standard spectrophotometric
      and fluorometric methods. Salivary GSH/GSSG and urinary AOPP were higher in
      females. Urinary fructosamine, GSH/GSSG and FRAP were higher in males. Urinary
      TAC and FRAP negatively correlated with age, and urinary GSH/GSSG positively
      correlated with weight. We determined that urine and saliva can be obtained non
      invasively from mice, in sufficient amounts for reliable oxidative status
      assessment. Further studies are needed to uncover whether these biofluids reflect
      systemic oxidative status in diseases.

PMID- 30204461
TI  - Ventilation distribution, pulmonary diffusion and peripheral muscle endurance as
      determinants of exercise intolerance in elderly patients with chronic obstructive
      pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD) is a progressive and disabling
      disease that has been associated with aging. Several factors may potentially
      impair performance during exercise in elderly patients with COPD. This study was
      conducted to evaluate what characteristics related to lung function, peripheral
      muscle strength and endurance can predict the performance of elderly patients
      with COPD during cardiopulmonary exercise testing (CPET). Forty elderly patients
      with COPD underwent resting lung function tests, knee isokinetic dynamometry, and
      CPET. Three models were developed to explain the variability in peak oxygen
      uptake (VO(2) peak) after controlling for age as an independent confounder. The
      pulmonary function model showed the highest explained variance (65.6%); in this
      model, ventilation distribution (p<0.001) and pulmonary diffusion (0.013) were
      found to be independent predictors. Finally, the models that included the muscle
      strength and endurance variables presented explained variances of 51% and 57.4%,
      respectively. In these models that involved muscular dysfunction, however, only
      the endurance variables were found to be independent predictors (p<0.05). In
      conclusion, ventilation distribution and pulmonary diffusion, but not the degree
      of airway obstruction, independently predict CPET performance in elderly patients
      with COPD. In addition, peripheral muscle endurance, but not strength, also
      predicts CPET performance in these subjects.

PMID- 30204462
TI  - The effect of selected feed mixtures on the duodenal morphology.
AB  - The objective of this work was to compare the effect of selected feed mixtures on
      the duodenal morphology. One-hundred-four rats of the Wistar strain were divided
      to thirteen groups per eight rats. The experiment started at 35-days rats after
      birth and lasted for 32-days. The groups (A-M) were fed; commercial diet, 85%
      wheat and 15% oat diet, 85% wheat and 15% triticale, 85% wheat and 15% barley,
      85% wheat and 15% amaranth, 85% wheat and 15% lantern, 85% wheat and 15%
      buckwheat, 100% wheat, 100% white lupine, 100% flock peas - variety Garden, 100%
      native peas - variety Garden, 100% native peas - variety Zekon or 100% extruded
      peas - variety Zekon diet respectively. Samples from the duodenum were taken. The
      height of the villi and the depth of the crypts were measured. The tallest villi
      were measured in group F (474.33+/-114.36 microm) and the shortest villi were
      observed in group B (294.08+/-88.52 microm). The deepest crypts were measured in
      group K (166.41+/-35.69 microm) and the shallowest crypts were observed in group
      E (77.85+/-17.61 microm). The work document, that gluten-free and classical
      cereals combination can be a better choice for people who want to limit the
      gluten content of the diet.

PMID- 30204463
TI  - Fast tonotopy mapping of the rat auditory cortex with a custom-made electrode
      array.
AB  - We present a custom-made multielectrode array for the recording of evoked
      potentials during acute experiments in rats, which offers a quick and reliable
      estimation of the cortical tonotopy. The array consists of electrodes represented
      by insulated copper wires of 0.09 mm diameter fixed in epoxy resin in a 3 x 5
      arrangement, with final impedances of 410 - 800 k Ohm. The array was placed on
      the brain surface of anaesthetized rats approximately at the location of the
      auditory cortex (AC) and the cortical evoked potentials (middle-latency
      responses, MLR) were elicited by a series of tone pips of different frequencies
      at 50 dB SPL intensity. The frequency that evoked the highest MLR amplitude (best
      frequency, BF) was identified for each electrode. The obtained distribution of
      the BFs characterised the cortical tonotopy, and it correlated with the frequency
      selectivity of neurones recorded at the same positions by an extracellular
      microelectrode. Although the space resolution of the array did not allow for the
      identification of AC sub regions, the array proved to be a reliable tool for a
      quick estimation and prediction of areas of interest for the subsequent
      measurements of neurones by more precise techniques.

PMID- 30204464
TI  - Relationship between dynamic expiratory time constant tau(edyn) and parameters of
      breathing cycle in pressure support ventilation mode.
AB  - Study of the relationship between ventilation parameters: monitored expiratory
      time constant - tau(edyn) and breathing - trigger frequency (f(trig)) and time of
      breathing cycle (T(cy)) are main goals of this article. Parameters were analyzed
      during last 4 hour +/- 2 before weaning from ventilation in 66 patients
      ventilated in pressure support mode (PSV). We have found out, that there exist
      mathematical relationships, observed during adequate gas exchange, yet not
      described. Monitored parameters are represented by: tau(edyn), f(trig) and T(cy).
      The analysis showed close negative correlation between T(cy) and f(trig) (R(2) = 
      0.903). This implies that each increasing of tau(edyn) causes decreasing of
      f(trig) and vice versa. The calculation of regression equation between tau(edyn)
      and T(cy) outlined, that T(cy) = 5.2625 * tau(edyn) + 0, 1242 (R(2) = 0.85).
      Regulation of respiratory cycles by the respiratory centre in the brain is
      probably based on evaluation of tau(edyn) as the tau(edyn) probably represents a
      regulatory element and T(cy) regulated element. It can be assumed, that
      respiratory centre can optimize the work of breathing in order to minimize energy
      in system patient + ventilator. The unique relationship, described above could be
      useful in clinical practice for development of new ventilation modes.

PMID- 30204465
TI  - Prenatal caffeine damaged learning and memory in rat offspring mediated by
      ARs/PKA/CREB/BDNF pathway.
AB  - Prenatal exposure to caffeine can cause developmental problems. This study
      determined chronic influence of prenatal caffeine at relatively higher doses on
      cognitive functions in the rat offspring. Pregnant Sprague-Dawley rats (4-month
      old) were exposed to caffeine (20 mg/kg, twice a day) for whole pregnancy from
      gestational day 4. Fetal and offspring body and brain weight was measured.
      Learning and memory were tested in adult offspring with Morris water maze;
      Learning and memory-related receptors were measured. The exposure to prenatal
      caffeine not only caused fetal growth restriction, but also showed long-term
      effects on learning and memory in the offspring. The caffeine offspring exhibited
      longer escape latency and path length in navigation testing. The number of
      passing the target was significantly reduced in those offspring. The expression
      of adenosine A(1) and A(2A) receptors, nuclear PKA C(alpha), C(beta) subunits,
      and pCREB were significantly increased in the fetal and neonatal brain, and
      suppressed in the hippocampus of the adult offspring. The expression of BDNF and
      TrkB were reduced regardless of various ages. The results suggest that
      intrauterine programming dysfunction of adenosine receptors and the down-stream
      of cAMP/PKA/pCREB system may play an important role in prenatal caffeine induced
      cognition disorders in the adult offspring.

PMID- 30204466
TI  - Plethysmographic and biochemical markers in the diagnosis of endothelial
      dysfunction in pediatric acute lymphoblastic leukemia survivors - new
      applications.
AB  - Acute lymphoblastic leukemia (ALL) and its treatment are associated with
      endothelial dysfunction (ED) and increased cardiovascular risk in adulthood.
      There are no data on ED in children after successful treatment of ALL. We aimed
      to assess new ED in these children using the plethysmographic Reactive Hyperemia
      Index (RHI) and biomarkers that are known to be related to ED. In all, 22
      children (mean 15.6 yrs.), after successful treatment of ALL, and 18 healthy
      subjects were included in this prospective study. RHI, plasma concentrations of
      asymmetric dimethyl arginine (ADMA), high-sensitive CRP (hsCRP) and E-selectin
      were measured in all children. RHI values were significantly lower in ALL
      patients when compared with healthy controls (p<0.05). hsCRPwas significantly
      increased in ALL patients compared with the control group (p<0.001). E-selectin
      plasma levels were higher in ALL patients as compared to healthy controls
      (p=0.05). This is the first study that combines both plethysmographic and
      biochemical methods to assess ED in ALL survivors. Significantly decreased RHI
      with elevated plasma concentrations of biochemical markers imply a possible
      association with premature ED in ALL patients. The combined diagnostic approach
      seems to be a valuable tool for more accurate detection of ED and preventive
      cardiovascular management in these patients.

PMID- 30204468
TI  - Application of adult mesenchymal stem cells in bone and vascular tissue
      engineering.
AB  - Tissue engineering is a very promising field of regenerative medicine. Life
      expectancy has been increasing, and tissue replacement is increasingly needed in
      patients suffering from various degenerative disorders of the organs. The use of
      adult mesenchymal stem cells (e.g. from adipose tissue or from bone marrow) in
      tissue engineering seems to be a promising approach for tissue replacements.
      Clinical applications can make direct use of the large secretome of these cells,
      which can have a positive influence on other cells around. Another advantage of
      adult mesenchymal stem cells is the possibility to differentiate them into
      various mature cells via appropriate culture conditions (i.e. medium composition,
      biomaterial properties, and dynamic conditions). This review is focused on
      current and future ways to carry out tissue replacement of damaged bones and
      blood vessels, especially with the use of suitable adult mesenchymal stem cells
      as a potential source of differentiated mature cells that can later be used for
      tissue replacement. The advantages and disadvantages of different stem cell
      sources are discussed, with a main focus on adipose-derived stem cells. Patient
      factors that can influence later clinical applications are taken into account.

PMID- 30204467
TI  - Effect of diabetes mellitus type 1 diagnosis on the corneal cell densities and
      nerve fibers.
AB  - Relation of diabetes mellitus (DM) to the various stages of corneal nerve fiber
      damage is well accepted. A possible association between changes in the cornea of
      diabetic patients and diabetic retinopathy (DR), DM duration, and age at the time
      of DM diagnosis were evaluated. The study included 60 patients with DM type 1
      (DM1) and 20 healthy control subjects. The density of basal epithelial cells,
      keratocytes and endothelial cells, and the status of the subbasal nerve fibers
      were evaluated using in vivo corneal confocal microscopy. Basal epithelial cell
      density increased with age (p=0.026), while stromal and endothelial cell density
      decreased with age (p=0.003, p=0.0005, p<0.0001). After the DM1 diagnosis was
      established, this association with age weaken. We showed nerve fiber damage in
      DM1 patients (p<0.0001). The damage correlated with the degree of DR. DM1
      patients with higher age at DM1 diagnosis had a higher nerve fiber density
      (p=0.0021). This results indicated that age at DM1 diagnosis potentially has an
      important effect on final nerve fiber and corneal cell density.

PMID- 30204469
TI  - Acute toxic effects of telmisartan in spontaneously hypertensive rats fed a high
      fructose diet.
AB  - Telmisartan is an angiotensin receptor blocker (ARB) and a selective peroxisome
      proliferator activated receptor gamma (PPARG) modulator. Recently, we tested
      metabolic effects of telmisartan (5 mg/kg body weight) in spontaneously
      hypertensive rats (SHR) fed a diet containing 60% fructose, a widely used model
      of the metabolic syndrome. Surprisingly, we observed acute toxic effects of
      telmisartan. Rats lost body weight rapidly and died within 2 to 3 weeks due to
      bleeding into the upper gastrointestinal tract. SHR fed a high fructose diet and
      treated with telmisartan exhibited rapid decrease in blood pressure when compared
      to the SHR fed a high fructose diet and treated with valsartan. Concentrations of
      both unconjugated telmisartan and telmisartan glucuronide in the liver of SHR
      rats fed a high fructose diet were approximately 4 fold higher when compared to
      Brown Norway (BN) rats fed the same diet. Plasma concentrations of unconjugated
      telmisartan in the SHR were about 5 fold higher when compared to BN rats while
      plasma levels of telmisartan glucuronide were similar between the strains.
      Testing of other rat strains, diets, and the ARB valsartan showed that toxic
      effects of telmisartan in combination with high fructose diet are specific for
      the SHR. These results are consistent with the possibility that in some
      circumstances, SHR are predisposed to telmisartan toxicity possibly because of a
      genetically determined disturbance in telmisartan metabolism.

PMID- 30204471
TI  - Changes in omentin levels and its mRNA expression in epicardial adipose tissue in
      patients undergoing elective cardiac surgery: the influence of type 2 diabetes
      and coronary heart disease.
AB  - Omentin is a protein produced by numerous tissues including adipose tissue. Its
      concentrations are decreased in patients with obesity, type 2 diabetes mellitus
      (DM) and coronary artery disease (CAD). Experimental studies suggest that omentin
      may have anti-inflammatory and insulin-sensitizing properties. In the present
      study, we measured circulating omentin levels and its mRNA expression in
      epicardial and subcutaneous fat, intercostal and heart muscle before and after
      elective cardiac surgery in patients with CAD (CAD+, DM-, n=18), combination of
      CAD and DM (CAD+, DM+, n=9) or with none of these conditions (CAD-, DM-, n=11).
      The groups did not differ in baseline anthropometric and biochemical
      characteristics with the exception of higher blood glucose and HBA1c in CAD+, DM+
      group. Baseline circulating omentin levels tended to be lower in CAD+, DM- and
      CAD+, DM+ groups as compared to CAD-, DM- group and cardiac surgery increased its
      concentration only in CAD-, DM- group. The change in serum omentin levels during
      surgery inversely correlated with epicardial fat thickness. While baseline
      omentin mRNA expression did not differ among the groups in any of the studied
      tissues, its increase after surgery was present only in subcutaneous fat in CAD-,
      DM- and CAD+, DM- groups, but not in CAD+, DM+ group. Intercostal muscle omentin
      mRNA expression increased after surgery only in CAD-, DM- group. In conclusion,
      cardiac surgery differentially affects omentin levels and subcutaneous fat and
      skeletal muscle mRNA expression in patients without coronary artery disease and
      diabetes as compared to patients with these conditions.

PMID- 30204470
TI  - Serum hepcidin is increased in ANCA-associated vasculitis and correlates with
      activity markers.
AB  - Hepcidin is a key regulator of iron metabolism and plays an important role in
      many pathologies. It is increased by iron administration and by inflammation,
      while erythropoiesis downregulates its expression. It decreases iron availability
      and thus contributes to anemia of chronic diseases. The aim of the study was to
      measure hepcidin as a marker and pathogenic factor in ANCA-associated vasculitis
      (AAV). Hepcidin plasma concentration was measured by the immunological method in
      59 patients with AAV and compared to patients with non-vasculitic etiology of
      chronic kidney disease, patients on hemodialysis (HD), with systemic lupus
      erythematodes (SLE) and to healthy controls and blood donors, and was correlated
      with the parameters of iron metabolism, inflammation, activity of the process and
      kidney function. Hepcidin concentration was increased in patients with AAV, SLE
      and HD and correlated positively with C-reactive protein, serum ferritin and
      creatinine, and negatively with hemoglobin and serum transferrin. In active form
      of AAV it correlated with the clinical scoring system (BVAS). Hepcidin can thus
      be considered as a pathogenetic factor of anemia in AAV and can be used for
      evaluation of inflammation in AAV and as an additional marker in active forms of
      the disease.

PMID- 30204472
TI  - Postural changes during quiet stance and gait initiation in slightly obese
      adults.
AB  - The study is aimed to examine balance control of slightly obese young adults
      during quiet stance and during gait initiation with and without crossing an
      obstacle. Forty-four young subjects were divided in two groups: control (BMI<25
      kg/m(2)) and slightly obese (BMI from 25 to 35 kg/m(2)). Center of foot pressure
      (CoP) and kinematics of fifth lumbar vertebra (L5) were evaluated using a force
      plate and a motion capture system. During quiet stance with eyes open slightly
      obese group showed increased mean amplitude and velocity of CoP in anterior
      posterior direction compared to normal weight subjects. During unloading phase of
      gait initiation significantly greater and faster lateral CoP shift was observed
      in slightly obese group compared to normal weight peers. Presence of an obstacle
      increased amplitude and velocity of the lateral CoP shift similarly in both
      groups. No BMI-related differences were found on L5 segment during gait
      initiation, which may indicate that postural control was already successfully
      performed in feet (CoP). We have shown that increased CoP parameters values and
      thus increased postural instability during quiet stance and during unloading
      phase of gait initiation is present not only in morbidly obese, but already in
      slightly obese subjects.

PMID- 30204473
TI  - Evaluation of later morphologic alterations in renal artery wall and renal nerves
      in response to catheter-based renal denervation in sheep: comparison of the
      single-point and multiple-point ablation catheters.
AB  - This study evaluated the subacute morphologic alterations in renal artery wall
      and renal nerves in response to catheter-based renal denervation in sheep and
      also compared the efficiency of single-point and multiple-point ablation
      catheters. Effect of each ablation catheter approved for the clinical use
      (Symplicity Flex(TM), Medtronic, INC. or EnligHTN(TM), St. Jude Medical, INC.)
      was compared to intact contralateral renal artery in 12 sheep by histopathology
      and immunohistochemistry evaluation after a 10-day period post RDN procedure. The
      safety was verified by extensive evaluation of kidney morphology. Vascular wall
      lesions and nerve injuries were more pronounced in those animals treated with
      multi-point EnligHTN catheter when compared with animals treated with single
      point Symplicity Flex catheter. However; neither RDN procedure led to complete
      renal nerve ablation. Both systems, tested in the present study, provided only
      incomplete renal nerve ablation in sheep. Moreover, no appreciable progression of
      the nerve disintegration in subacute phase post-RDN procedure was observed. This
      study further supports the notion that the effectiveness remains fully dependent
      on anatomical inter-individual variability of the sympathetic nerve plexus
      accompanying the renal artery. Therefore, new systems providing deeper penetrance
      to targeted perivascular structure would be more efficient.

PMID- 30204474
TI  - Umbilical Mononuclear Cells and Fibroblast Interaction Downregulate the
      Expression of Cell Cycle Negative Control Genes.
AB  - The human umbilical cord blood (HUCB) is an excellent source of adult stem cells,
      having the benefit of being younger than the bone marrow stem cells. The role of
      stem cells in the lesion repair mechanism is still being studied. We evaluated
      the capability of HUCB to interfere into the fibroblast dedifferentiation
      plasticity through cocultivation. Direct and indirect cocultures were maintained
      for 24, 48, and 72 hours. Coculture viability was evaluated by MTT assay. The
      messenger RNA was extracted, and the expression of p16 and p21 genes was
      estimated by quantitative reverse transcriptase polymerase chain reaction (qRT
      PCR). The direct or indirect contact did not interfere with fibroblast cell
      viability. However, these direct and indirect contacts reduced the expression of
      p16 and p21 genes. A sigmoidal curve was applied to adjust gene expression
      against time, and a mathematical function was established for gene expression
      according to cell culture type. These results suggest that the differentiated
      cells were influenced by immature cells (HUCB) either by the direct contact or by
      signaling molecules, which alter their behavior and plasticity. Therefore our
      data may contribute to paracrine effects other than the commonly known to be
      responsible for the repair of lesions in stem cell therapy.

PMID- 30204475
TI  - Diet Supplemented with Chia Flour did not Modified the Inflammatory Process and
      Tumor Development in Wistar Rats Inoculated with Walker 256 Cells.
AB  - Chia seed (Salvia hispanica L.) contains high amounts of n-3 alpha-linolenic acid
      (ALA) and has been associated with many health benefits. The aim of the present
      study was to evaluate the AIN-93 diet supplemented by chia flour on cancer
      cachexia development and tissues inflammatory response. Wistar rats at 30 days
      old were treated with control diet or diet supplemented with chia flour for eight
      weeks. After this period, half of the animals in each diet group were inoculated
      with Walker 256 tumor cells. On the 14th day after tumor inoculation, the animals
      were euthanized and white adipose tissue depots, liver, gastrocnemius muscle, and
      tumor were removed. The tumor weight was higher and IL-10 content was lower in
      chia flour group. The tumor bearing did not modify the cytokines content in
      gastrocnemius muscle, retroperitoneal and epididymal adipose tissue, however, it
      decreased IL-1beta and TNF-alpha content in liver, and IL6R and IL-10R protein
      content in mesenteric adipose tissue. In conclusion, our results demonstrated
      that supplementation with chia flour did not prevent the tumor bearing effects in
      Walker 256 model.

PMID- 30204477
TI  - The Insight into Protein-Ligand Interactions, a Novel Way of Buffering Protein
      Noise in Gene Expression.
AB  - Random fluctuations are often considered detrimental in the context of gene
      regulation. Studies aimed at discovering the noise-buffering strategies are
      important. In this study, we demonstrated a novel design of attenuating noise at
      protein-level. The protein-ligand interaction dramatically reduced noise so that
      the coefficient of variation (COV) became roughly 1/3. Remarkably, in comparison
      to the other two noise-buffering methods, the negative feedback control and the
      incoherent feedforward loop, the COV of the target protein in the case of protein
      ligand interaction appeared to be less than 1/2 of that of the other two methods.
      The high correlation of the target protein and the ligand grants the present
      method great ability to buffer noise. Further, it buffers noise at the stage
      after translation so it is also capable of attenuating the noise inherited from
      the process of translation.

PMID- 30204478
TI  - A Rapid and Highly Efficient Method for the Isolation, Purification, and
      Passaging of Human-Induced Pluripotent Stem Cells.
AB  - Human-induced pluripotent stem cells (iPSCs) hold considerable promise for future
      biomedical applications. However, the generation, isolation, and establishment of
      an iPSC line still presents many challenges. In this study, we describe a simple
      yet highly efficient two-step method for the isolation, purification, and
      passaging of human iPSC lines that utilizes commercially available reagents. The
      first step adapts iPSCs to single cell culture and passage, promoting survival
      and self-renewal; the second step enables the isolation and purification of bona
      fide iPSCs from a mixed population using column-based positive selection of cells
      expressing pluripotency markers such as TRA-1-60. Using this method, we were able
      to purify iPSCs from cell preparations containing differentiated or
      unreprogrammed cells, and even to isolate iPSC lines directly from derivation
      plates. The iPSC lines generated by this method maintained their pluripotency and
      genomic stability, as demonstrated by trilineage differentiation and karyotype
      analysis. The method presented here could be adopted for high-throughput
      isolation and expansion of iPSC lines and facilitate the widespread use of iPSCs
      in future applications.

PMID- 30204479
TI  - Bixin Triggers Apoptosis of Human Hep3B Hepatocellular Carcinoma Cells: An
      Insight to Molecular and IN SILICO Approach.
AB  - Hepatocellular carcinoma (HCC) is the most common liver cancer and is known to be
      resistant to conventional chemotherapy. The use of herbal medicine and
      supplements has increased over recent decades following side effects and
      resistant to conventional chemotherapy. The seeds of Bixa orellana L. commonly
      known as annatto have recently gained scientific attention due to presence of a
      carotenoid bixin for its substantial anticancer properties. However, molecular
      mechanisms underlying bixin-induced apoptosis are still unclear. Treatment of
      bixin significantly decreased the number of Hep3B cells and morphological study
      revealed the change in cellular and nuclear morphology that trigger the events of
      apoptosis confirmed by annexin V/PI staining. Further DCFDA and rhodamine 123
      spectrofluorimetry study showed elevation in reactive oxygen species (ROS)
      production and loss of mitochondrial membrane potential (MMP), respectively. ROS
      production caused DNA damage and apoptosis was marked by cell cycle arrest, up
      regulation of Bax and FasL protein as well as cleavage of caspase-9, caspase-8
      and caspase-3 protein. Docking study with pro-apoptotic molecule Bax and surface
      Fas ligand exhibited energetically favourable binding interaction. Collectively,
      these results suggest that bixin capable of modulating the extrinsic and
      intrinsic molecules of apoptosis indicating its potential for development of
      promising candidate for hepatocellular carcinoma.

PMID- 30204481
TI  - Large-Deviation Properties of Sequence Alignment of Correlated Sequences.
AB  - The significance of alignment scores of optimally aligned DNA sequences can be
      estimated through the score distribution of pairs of random sequences. It is
      necessary to obtain statistics for the relevant high-scoring tail of the
      distribution. For local alignments of iid drawn sequences it has already been
      shown that the often assumed Gumbel distribution does not hold in the
      distribution tail, but has to be corrected by a Gaussian factor. Real DNA
      sequences were observed to show long-range correlations within sequences, which
      are not correctly modeled by iid random sequences. In this publication the large
      deviation method that was used in previous studies is applied to local and global
      alignment of such sequences with long-range correlations. We study the
      distributions over the full range of the support and obtained probabilities as
      low as [Formula: see text]. We show that again a correction to the Gumbel
      distribution is necessary to study the dependence of the parameters on the
      correlation strength. For global alignments the Gamma distribution, which was
      found heuristically to be a good fit in earlier simple sampling studies, is found
      to be a poor fit.

PMID- 30204480
TI  - Machine Learning-Based Method for Obesity Risk Evaluation Using Single-Nucleotide
      Polymorphisms Derived from Next-Generation Sequencing.
AB  - Obesity is a major risk factor for many metabolic diseases. To understand the
      genetic characteristics of obese individuals, single-nucleotide polymorphisms
      (SNPs) derived from next-generation sequencing (NGS) provide comprehensive
      insight into genome-wide genetic investigation. However, interpretation of these
      SNP data for clinical application is difficult given the high complexity of NGS
      data. Hence, in this study, obesity risk prediction models based on SNPs were
      designed using machine learning (ML) methods, namely support vector machine
      (SVM), k-nearest neighbor, and decision tree (DT). This investigation obtained
      clinicopathological features, including 130 SNPs, sex, and age, from 139 eligible
      individuals. Various feature selection methods, such as stepwise multivariate
      linear regression (MLR), DT, and genetic algorithms, were applied to select
      informative features for generating obesity prediction models. Multivariate
      logistic regression was used to evaluate the importance of the selected features.
      The models trained from various features evaluated their predictive performances
      based on fivefold cross-validation. Three measures, namely accuracy, sensitivity,
      and specificity, were used to examine and compare the predictive power among
      various models. To design obesity prediction models using ML methods, nine SNPs,
      including rs10501087, rs17700144, rs2287019, rs534870, rs660339, rs7081678,
      rs718314, rs9816226, and rs984222, were selected based on stepwise MLR. In
      evaluation of model performance, the SVM model significantly outperformed other
      classifiers based on the same training features. The SVM model exhibits 70.77%
      accuracy, 80.09% sensitivity, and 63.02% specificity. This investigation has
      demonstrated that the selected SNPs were effective in the detection of obesity
      risk. Additionally, the ML-based method provides a feasible mean for conducting
      preliminary analyses of genetic characteristics of obesity.

PMID- 30204482
TI  - EasyQC: Tool with Interactive User Interface for Efficient Next-Generation
      Sequencing Data Quality Control.
AB  - The advent of next-generation sequencing (NGS) technologies has revolutionized
      the world of genomic research. Millions of sequences are generated in a short
      period of time and they provide intriguing insights to the researcher. Many NGS
      platforms have evolved over a period of time and their efficiency has been ever
      increasing. Still, primarily because of the chemistry, glitch in the sequencing
      machine and human handling errors, some artifacts tend to exist in the final
      sequence data set. These sequence errors have a profound impact on the downstream
      analyses and may provide misleading information. Hence, filtering of these
      erroneous reads has become inevitable and myriad of tools are available for this
      purpose. However, many of them are accessible as a command line interface that
      requires the user to enter each command manually. Here, we report EasyQC, a tool
      for NGS data quality control (QC) with a graphical user interface providing
      options to carry out trimming of NGS reads based on quality, length, homopolymer,
      and ambiguous bases. EasyQC also possesses features such as format converter,
      paired end merger, adapter trimmer, and a graph generator that generates quality
      distribution, length distribution, GC content, and base composition graphs.
      Comparison of raw and processed sequence data sets using EasyQC suggested
      significant increase in overall quality of the sequences. Testing of EasyQC using
      NGS data sets on a standalone desktop proved to be relatively faster. EasyQC is
      developed using PERL modules and can be executed in Windows and Linux platforms.
      With the various QC features, easy interface for end users, and cross-platform
      compatibility, EasyQC would be a valuable addition to the already existing tools
      facilitating better downstream analyses.

PMID- 30204483
TI  - A Slow-Digesting, Low-Glycemic Load Nutritional Beverage Improves Glucose
      Tolerance in Obese Pregnant Women Without Gestational Diabetes.
AB  - BACKGROUND: Obesity is a risk factor for gestational diabetes (gestational
      diabetes). Low-glycemic index diets attenuate hyperglycemia. We designed a study
      to determine whether a slow-digesting, low-glycemic load (SD-LGL) beverage
      improves glucose tolerance in obese pregnant women without GDM. METHODS: This was
      a 3-arm comparison study comparing the effects of an SD-LGL nutritional beverage
      (glycemic load [GL] 730), an isocaloric control beverage (GL 1124), and habitual
      diet on glycemia in obese pregnant women. Sixteen women (mean body mass index 37
      kg/m2) were recruited at 24-28 weeks to receive either the SD-LGL or eucaloric
      control beverage. This was consumed with breakfast and as a midafternoon snack
      over 2 days with a controlled diet. Following a 2-day washout period of habitual
      diet, women completed 2 days on the alternative beverage with controlled diet. A
      10-h fast preceded each intervention phase. Twenty-four hour glucose was measured
      using continuous glucose monitoring. RESULTS: Consumption of the lower GL
      beverage was associated with improved measures of glycemia, compared with the
      control beverage and habitual diet at different time periods. Glucose estimates
      for control versus SD-LDL at 24 h (0.23 mmol/L [0.16 to 0.31], P < 0.001),
      daytime (0.26 mmol/L [0.18 to 0.34], P < 0.001), and nighttime (0.05 mmol/L [
      0.01 to 0.11], P = 0.09). Postprandial glucose was lower after breakfast but not
      after dinner, compared with the control beverage (0.09 mmol/L [0.01 to 0.18], P =
      0.03). CONCLUSION: A slow-digesting, low-glycemic nutritional beverage may
      facilitate improved glucose control in obese pregnant women. To address potential
      benefit for clinical outcomes, a randomized controlled trial is warranted.

PMID- 30204484
TI  - A Combination of Moringin and Avenanthramide 2f Inhibits the Proliferation of
      Hep3B Liver Cancer Cells Inducing Intrinsic and Extrinsic Apoptosis.
AB  - Moringin (MOR), a glycosyl-isothiocyanate obtained by myrosinase-catalyzed
      hydrolysis of the precursor 4-(alpha-l-rhamnosyloxy)-benzyl glucosinolate
      (glucomoringin), found predominantly in the seeds of Moringa oleifera, shows
      anticancer effects against several cancer cell lines. Avenanthramide (AVN) 2f is
      a phytochemical purified from oats with antioxidant and anticancer properties.
      The aim of this study was to investigate the antiproliferative and proapoptotic
      effects of MOR and AVN 2f used alone and in combination on Hep3B cancer cells,
      which are highly resistant to conventional anticancer drugs. We found that a
      cocktail of MOR and AVN 2f significantly inhibited the Hep3B proliferation rate
      by markedly increasing the activity of caspases 2, 8, 9, and 3. Extrinsic
      apoptosis was induced by the AVN 2f-mediated activation of caspase 8, while the
      intrinsic apoptotic pathway was triggered by MOR-induced increase in the levels
      of intracellular reactive oxygen species, MOR-mediated activation of caspases 2
      and 9 and the MOR-mediated downregulation of the prosurvival gene BIRC5. Our
      results suggest that the combination MOR + AVN 2f could be an effective
      chemopreventive cocktail against the development of hepatocarcinoma.

PMID- 30204485
TI  - DHA but not AA Enhances Cisplatin Cytotoxicity in Ovarian Cancer Cells.
AB  - Clinical and epidemiological studies show that docosahexaenoic acid (DHA) and
      arachidonic acid (AA) exert multiple effects on ovarian cancer. While DHA seems
      to inhibit growth and prevent carcinogenic processes, stimulation of leukotriene
      B4 receptors BLT1 and BLT2 by several eicosanoids derived from AA plays an
      important role in mediating cisplatin resistance in ovarian cancer cells. We
      examined whether DHA and AA exerted antiproliferative effect on epithelial
      ovarian cancer cells and whether these polyunsaturated fatty acids could alter
      their susceptibility to cisplatin. Using SKOV3 and OVCAR3 cell lines, we found
      that DHA but not AA suppressed the cells viability, proliferation, enhanced cell
      death, and induced activation of caspase-3/7 in the concentration- and time
      dependent manner. The OVCAR3 cells were less susceptible to cisplatin than SKOV3
      cells. DHA but not AA significantly potentiated cisplatin cytotoxicity in SKOV3
      and OVCAR3 cells. We did not observe any significant influence of AA on the above
      mentioned processes in both cell lines. Similar effect can occur in ovarian
      cancer patients treated with cisplatin and supplemented with DHA.

PMID- 30204486
TI  - Performance of Medtronic Hybrid Closed-Loop Iterations: Results from a Randomized
      Trial in Adolescents with Type 1 Diabetes.
AB  - This study investigates the performance of an iteration of the Medtronic hybrid
      closed-loop (HCL) algorithm, which utilizes sensor glucose values non
      adjunctively for bolus advice, recognizes sustained hyperglycemia, suggests
      insulin bolus correction, and includes more accommodative SmartGuardTM automode
      parameters that aim to improve function and usability. Adolescents aged 13-17
      years with type 1 diabetes >1 year, glycated hemoglobin (HbA1c) 7.0%-10%,
      currently using Continuous Subcutaneous Insulin Infusion were randomized to the
      control Medtronic standard HCL algorithm or to the intervention Medtronic HCL
      with enhancements. Participants attended a 7-day and 7-night nonstructured camp
      setting. Twelve participants (mean age 15 years, seven males, five females, mean
      HbA1c 8.55%) completed the study. For the control group, time in target glucose
      sensor range (3.9-10 mmol/L) was 63.68% +/- 10.74% at baseline and changed to
      75.85% +/- 8.49% during the study (relative Delta19%). Time spent in <2.8 mmol/L
      was 0.61% +/- 0.79% at baseline for the control group and changed to 0.32% +/-
      0.31% during the study for the control group (relative Delta48%). In the
      intervention group, time in target glucose sensor range (3.9-10 mmol/L) was
      52.15% +/- 9.55% at baseline and changed to 74.32% +/- 8.41% during the study
      (relative Delta42%). Time spent in <2.8 mmol/L was 1.07% +/- 1.77% at baseline
      for the intervention group and changed to 0.24% +/- 0.14% during the study for
      the intervention group (relative Delta78%). Mean sensor glucose was 8.05 +/- 0.73
      mmol/L and 8.22 +/- 0.56 mmol/L for the control and intervention participants.
      SmartGuard automode exit frequency was 0.54 exits per person per day for control
      and 0.12 exits per person per day for the intervention. Participants were in
      active SmartGuard automode 97.1% and 98.8% of the time for the control and
      intervention, respectively. Alarm frequency was 2.1 alarms per person per day for
      the control arm, and 0.26 alarms per person per day in the intervention arm.
      Feasibility of the enhanced HCL algorithm was demonstrated with a high proportion
      of time spent in SmartGuard automode and target glucose range. The iterative
      changes resulted in less SmartGuard automode exits without compromising glycemic
      control.

PMID- 30204487
TI  - Comparison of Breast Milk Compositions Among Mothers Delivering Small-for
      Gestational Age, Appropriate-for-Gestational Age, and Large-for-Gestational Age
      Infants.
AB  - OBJECTIVES: The aim of this study was to compare the breast milk compositions of
      mothers who delivered babies in three different birth weight categories.
      MATERIALS AND METHODS: We collected 75 breast milk samples from mothers of small
      for-gestational age (SGA), appropriate-for-gestational age (AGA), and large-for
      gestational age (LGA) term infants (25 per group) on the 11th-28th day postpartum
      using a manual or electric breast pump. Homogenized samples were analyzed using a
      mid-infrared human milk analyzer within 2 hours of collection, and protein,
      carbohydrate (CHO), fat, and energy levels were compared. RESULTS: Of 75
      participants (median maternal age: 29 years), there was a significant difference
      in maternal body mass index (BMI), gestational age, and birth weight among the
      three groups. However, we found no significant variation in breast milk true
      protein, crude protein, fat, or energy. The CHO composition of breast milk in
      mothers of SGA infants (7.1 g/100 mL, range: 6.6-7.3 g/100 mL) was significantly
      lower than that in the AGA (7.3 g/100 mL, range: 7.1-7.5 g/100 mL) and LGA (7.2
      g/100 mL, range: 6.7-7.4 g/100 mL) groups. After post hoc multiple comparison,
      only CHO levels between the SGA and AGA groups were significantly different (p =
      0.025), whereas no significant correlation was found between maternal BMI,
      gestational age, and CHO. CONCLUSIONS: The CHO component in breast milk from
      mothers of SGA infants was significantly lower compared with the AGA and LGA
      groups, but with no clinical significance. Breast milk compositions of mothers of
      LGA infants were comparable to those of SGA and AGA infants. Therefore, fetal
      growth status does not significantly influence maternal breast milk nutrients.

PMID- 30204488
TI  - Mitochondrial Morphologies Driven by Energy-Consuming Cell Sites in a Spatially
      and Time-Resolved Quality Model.
AB  - Mitochondria are the energy plants of eukaryotic cells. Mitochondrial network
      morphologies are essential for the energy supply of eukaryotic cells. However,
      the associated dynamics are not yet fully understood. They behave as a dynamic
      network that adapts to the cell's environment and its energetic needs. Various
      processes such as mitochondrial fission and fusion, mitochondrial recycling,
      repair mechanisms, and oxidative stress influence the state of the mitochondrial
      network. Here, we introduce a novel time-dependent and spatially resolved quality
      model on mitochondrial morphology. The interplay between the mitochondrial
      network and energy-consuming cell sites is modeled by biophysical interactions of
      quality-dependent mitochondrial clusters in the presence of adenosine
      triphosphate (ATP) consumers represented by Mie potentials. Mitochondria are
      modeled as simplified ballistic particles that move within the cytoplasm of a
      virtual cell, and connect and divide by inelastic collisions. With this model, we
      investigate the coupling of mitochondrial dynamics with oscillating cell
      functions, representing diverse global states of the energetic architecture in
      the cell. Our simulations based on a generalized cell reveal a perinuclear
      condensation of mitochondria during phases of high-energy demand. Furthermore,
      quality-increasing mechanisms disclose the benefits of high mitochondrial masses.
      Simulations reveal that varying energy demands modeled by oscillations of ATP
      consumers alter the morphology of the network. Phases of high-energy consumption
      lead to interconnected network structures and perinuclear condensation of
      mitochondria. The model explains quality-increasing benefits of high
      mitochondrial masses.

PMID- 30204489
TI  - Sequence Alignment on Directed Graphs.
AB  - Genomic variations in a reference collection are naturally represented as genome
      variation graphs. Such graphs encode common subsequences as vertices and the
      variations are captured using additional vertices and directed edges. The
      resulting graphs are directed graphs possibly with cycles. Existing algorithms
      for aligning sequences on such graphs make use of partial order alignment (POA)
      techniques that work on directed acyclic graphs (DAGs). To achieve this, acyclic
      extensions of the input graphs are first constructed through expensive loop
      unrolling steps (DAGification). Furthermore, such graph extensions could have
      considerable blowup in their size and in the worst case the blow-up factor is
      proportional to the input sequence length. We provide a novel alignment algorithm
      V-ALIGN that aligns the input sequence directly on the input graph while avoiding
      such expensive DAGification steps. V-ALIGN is based on a novel dynamic
      programming (DP) formulation that allows gapped alignment directly on the input
      graph. It supports affine and linear gaps. We also propose refinements to V-ALIGN
      for better performance in practice. With the proposed refinements, the time to
      fill the DP table has linear dependence on the sizes of the sequence, the graph,
      and its feedback vertex set. We conducted experiments to compare the proposed
      algorithm against the existing POA-based techniques. We also performed alignment
      experiments on the genome variation graphs constructed from the 1000 Genomes
      data. For aligning short sequences, standard approaches restrict the expensive
      gapped alignment to small filtered subgraphs having high similarity to the input
      sequence. In such cases, the performance of V-ALIGN for gapped alignment on the
      filtered subgraph depends on the subgraph sizes.

PMID- 30204490
TI  - Spectral-Domain Optical Coherence Tomography for Determination of Retinal
      Thickness in Pediatric Patients with Mild-To-Moderate Chronic Kidney Disease: A
      Cross-Sectional Study.
AB  - OBJECTIVE: Children with chronic kidney diseases (CKD) are at risk for
      neurological diseases at early adulthood. Spectral-domain optical coherence
      tomography (SD-OCT) of the retina is especially suitable for determination of
      intraretinal layer thickness. We wonder whether retinal thinning is already
      present in pediatric patients with mild-to-moderate CKD. PATIENTS AND METHODS:
      Children (n = 15; 14.9 +/- 2.4 years) with mild-to-moderate CKD (median eGFR of
      95ml/min/1.73m2; range: 28-187ml/min/1.73m2) due to glomerulopathy, congenital
      anomalies of kidney and urinary tract (CAKUT), or haemolytic uremic syndrome
      (HUS) underwent a detailed ophthalmologic examination including high-resolution
      SD-OCT. Three OCT scans were obtained from the right eyes of all patients. Within
      each scan, retinal layers were separated and the mean thickness was determined at
      the foveal, parafoveal, and perifoveal area. The results were compared to those
      we obtained previously from healthy children. RESULTS: At the parafoveal area,
      thickness (median, range) of the total retina (ALL), ganglion cell layer (GCL),
      and inner plexiform layer (IPL) were reduced compared to healthy volunteers
      (339um, (288-361um) vs. 348um, (320-385um); 49.8um (30.5-56.6um) vs. 53.5MUm
      (49.5-60.5um) and 41.0um (29.4-43.7um) vs. 43.46um (39.5-46.3MUm); each p <
      0.05). The intraretinal thickness measurements at the foveal and perifoveal areas
      revealed no statistically significant differences between patients and controls.
      CONCLUSION: Distinct changes within the parafoveal area of the total retina, GCL,
      and IPL are present in children with mild-to-moderate CKD. Prospective studies
      are required to assess the clinical significance of our findings.

PMID- 30204491
TI  - Research advances in the regulation of the putative ovarian germline stem cell
      niche on female germline stem cells.
AB  - : Stem cells are ideal seeding cells, which have the potential for self-renewal
      and multiple differentiation, and they play a fundamental role in maintaining
      homeostasis and regenerating and repairing tissue. The discovery of female
      germline stem cells (FGSCs) brings much hope for the postnatal renewal of oocytes
      and solving some female infertility problems. Ovarian function declines with
      increasing female age. Moreover, ovarian germline stem cell niche-aging could be
      the main cause of ovarian senescence, which ultimately leads to decreased
      follicle generation, declining female fertility, and age-related diseases, such
      as osteoporosis and ovarian cancer. The ovarian germline stem cell niche is the
      surrounding microenvironment in which FGSCs live, and it helps control the
      biological characteristics of FGSCs in many ways, such as nutritional supply and
      immunological cytokine secretion. This paper reviews the knowledge about the
      ovarian germline stem cell niche and its probable regulatory mechanisms on FGSCs,
      which provides valuable scientific information and scope for the prevention and
      treatment of ovarian senescence. ABBREVIATIONS: BMP: bone morphogenetic protein;
      Dpp: decapentaplegic; FGSC: female germline stem cell; IL, interleukin; OGSC:
      ovarian germline stem cells; ROS: reactive oxygen species; TGF, transforming
      growth factor; TNF, tumor necrosis factor.

PMID- 30204492
TI  - Differing Approaches to Managing the Chronic Breathlessness Syndrome in Advanced
      COPD: A Multi-National Survey of Specialists.
AB  - This study explored the approaches of respiratory and palliative medicine
      specialists to managing the chronic breathlessness syndrome in patients with
      severe chronic obstructive pulmonary disease. A voluntary, online survey was
      emailed to all specialists and trainees in respiratory medicine in Australia and
      New Zealand (ANZ), and to all palliative medicine specialists and trainees in ANZ
      and the United Kingdom (UK). Five hundred and seventy-seven (33.0%) responses
      were received from 1,749 specialists, with 440 (25.2%) complete questionnaires
      included from 177 respiratory and 263 palliative medicine doctors. Palliative
      medicine doctors in ANZ and the UK had similar approaches to managing chronic
      breathlessness, whereas respiratory and palliative medicine doctors had
      significantly different approaches (p < 0.0001). Both specialties most commonly
      recommended a combination of non-pharmacological and pharmacological
      breathlessness management strategies. Respiratory doctors focussed more on
      pulmonary rehabilitation, whereas palliative medicine doctors recommended
      breathing techniques, anxiety management and the handheld fan. Palliative
      medicine doctors (197 (74.9%)) recommended short acting oral morphine for
      breathlessness, as compared with 73 (41.2%) respiratory doctors (p < 0.0001).
      Respiratory doctors cited opioid concerns related to respiratory depression and
      lack of knowledge. Nineteen (10.7%) respiratory doctors made no specific
      recommendations for managing chronic breathlessness. Both specialties reported
      actively managing chronic breathlessness, albeit with differing approaches.
      Integrated services, which combine the complementary knowledge and approaches of
      both specialities, may overcome current gaps in care and improve the management
      of distressing, chronic breathlessness.

PMID- 30204493
TI  - Effects of High-Intensity Interval Training Under Normobaric Hypoxia on
      Cardiometabolic Risk Markers in Overweight/Obese Women.
AB  - Camacho-Cardenosa, Alba, Marta Camacho-Cardenosa, Javier Brazo-Sayavera, Martin
      Burtscher, Rafael Timon, and Guillermo Olcina. Effects of high-intensity interval
      training under normobaric hypoxia on cardiometabolic risk markers in
      overweight/obese women. High Alt Med Biol. 16:000-000, 2018.-Promising benefits
      on cardiometabolic risk factors have been reported with prolonged programs of
      cyclic hypoxia. The aim of this study was to examine whether cyclic hypoxia
      exposure while exercising through two protocols of high-intensity interval
      training in overweight/obese women is more effective to improve cardiometabolic
      risk markers than exercising in normoxia. Participants included 86
      overweight/obese women, who started a 12-week program of 36 sessions, and were
      randomly divided into four groups: (1) interval training in hypoxia (IHT; FIO2 =
      17.2%; n = 13), (2) interval training in normoxia (INT; n = 15), which included 3
      minute high-intensity exercise (90% Wmax) followed by 3 minutes of active
      recovery (55%-65% Wmax), (3) repeated-sprint training in hypoxia (RSH; FIO2 =
      17.2%; n = 15), and (4) repeated-sprint training in normoxia (RSN; n = 18), which
      included 30 seconds of all-out effort (130% Wmax) followed by 3 minutes of active
      recovery (55%-65% Wmax). Body composition, anthropometric, biochemical, and
      clinical parameters were assessed at baseline (A), after 18 training sessions
      (B), and during the 7 days after the last session (C). IHT and RSH showed a
      significant (p < 0.001 and p = 0.016, respectively) decrease in the waist
      circumference at both B and C assessments compared with A. Hypoxia groups
      presented a significant reduction in the percentage of trunk fat with a moderate
      effect size (IHT: d = 0.56; RSH: d = 0.93). In the normoxia groups, total
      cholesterol (CHOL) tended to decrease (INT: -4.21% and RSN: -5.18%), whereas it
      tended to increase in the hypoxia groups (IHT: +2.91% and RSH +4.07%). An
      interaction effect between conditions (through pooled data) on waist
      circumference (p = 0.01), percentage of trunk fat mass (p < 0.001), and CHOL (p =
      0.019) was observed. Both training regimens under normobaric cyclic hypoxia were
      more effective at causing decreased abdominal fat in overweight/obese women than
      the same protocols in normoxia.

PMID- 30204494
TI  - Proposed Proarrhythmic Cardiac Safety Education in Medical, Pharmacy, and Nursing
      Schools: An Interprofessional Model.

PMID- 30204495
TI  - The Vegetation Red Edge Biosignature Through Time on Earth and Exoplanets.
AB  - The high reflection of land vegetation in the near-infrared, the vegetation red
      edge (VRE), is often cited as a spectral biosignature for surface vegetation on
      exoplanets. The VRE involves only a few percentage change in reflectivity for a
      disk-integrated observation of present-day Earth. Here we show that the strength
      of Earth's VRE has increased over the past ~500 million years of land plant
      evolution and may continue to increase as solar luminosity increases and the
      planet warms, until either vegetation coverage is reduced, or the planet's
      atmosphere becomes opaque to light reflected off the surface. Early plants such
      as mosses and liverworts, which dominated the land 500-400 million years ago,
      produce a weaker VRE, approximately half as strong as that of modern vegetation.
      We explore how the changes in land plants, as well as geological changes such as
      ice coverage during ice ages and interglacial periods, influence the
      detectability of the VRE through Earth's geological past. Our results show that
      the VRE has varied through the evolutionary history of land plants on Earth and
      could continue to change into the future if hotter climate conditions became
      dominant, encouraging the spread of vegetation. Our findings suggest that older
      and hotter Earth-like planets are good targets for the search for a VRE
      signature. In addition, hot exoplanets and dry exoplanets with some water could
      be the best targets for a successful vegetation biosignature detection. As well
      as a strong red edge, lower cloud fractions and low levels of atmospheric water
      vapor on such planets could make it easier to detect surface features in general.

PMID- 30204496
TI  - Molybdenum(VI)-Catalyzed Rearrangement of Prebiotic Carbohydrates in Formamide, a
      Candidate Prebiotic Solvent.
AB  - It has been four decades since formamide was first suggested to perform roles as
      a precursor and/or a solvent in prebiotic chemistry. However, little work has
      sought to integrate formamide into larger prebiotic schemes that might create
      prebiotic RNA, often proposed to have been the first Darwinian biopolymer. Here,
      we report that formamide can be used as a solvent to perform the Bilik reaction,
      which uses molybdenum(VI) oxo species as catalysts at near-neutral pH to
      rearrange branched carbohydrates to give linear carbohydrates; the branched
      carbohydrates are produced from formaldehyde (HCHO) in alkaline mixtures
      containing borate, whereas the linear carbohydrates are the precursors needed for
      ribonucleosides and ribonucleotides. Under conditions wherein the Bilik reaction
      does this rearrangement, carbohydrate reaction products do not require
      stabilization by borate. These results, therefore, connect aqueous and formamide
      based processes for the prebiotic formation of RNA components. Based on data from
      Hadean zircons that show that the mantle of the early Earth was near the fayalite
      quartz-magnetite fugacity, molybdenum in its 6+ oxidation state was likely
      available in the Hadean. Together, these allow us to conjecture a process that
      delivers ribonucleosides and ribonucleotides from hydrogen cyanide and HCHO from
      a Hadean atmosphere on a Hadean geosphere, without needing precisely timed
      transitions from one solvent system to the other.

PMID- 30204497
TI  - Rocky Planet Rotation, Thermal Tide Resonances, and the Influence of Biological
      Activity.
AB  - It has been established theoretically that atmospheric thermal tides on rocky
      planets can lead to significant modifications of rotational evolution, both close
      to synchronous rotation and at faster rotations if certain resonant conditions
      are met. Here it is demonstrated that the normally considered dissipative
      gravitational tidal evolution of rocky planet rotation could, in principle, be
      "stalled" by thermal tide resonances for Earth-analog worlds in the liquid-water
      orbital zone of stars more massive than [Formula: see text]. The possibility of
      feedback effects between a planetary biosphere and the planetary rotational
      evolution is examined. Building on earlier studies, it is suggested that
      atmospheric oxygenation and ozone production could play a key role in planetary
      rotational evolution, and therefore represents a surprising but potent form of
      biological imprint on astronomically accessible planetary characteristics.

PMID- 30204498
TI  - FGF2 Signaling Plays an Important Role in Maintaining Pluripotent State of Pig
      Embryonic Germ Cells.
AB  - Germ cells are alternative sources for deriving pluripotent stem cells. Because
      embryonic germ cells (EGCs) possess physiological and developmental features
      similar to those of embryonic stem cells, pig EGCs are considered a potential
      tool for generating transgenic animals for agricultural usage. Therefore, in this
      study, we attempted to establish and characterize pig EGCs from fetal gonads. EGC
      lines were derived from the genital ridges of porcine fetuses in media containing
      leukemia inhibitory factor (LIF), fibroblast growth factor 2 (FGF2), and stem
      cell factor. After establishment, these cells were cultured and stabilized in LIF
      or FGF2-containing media. The cell lines were maintained under both conditions
      over an extended time period and spontaneously differentiated into the three germ
      layers in vitro. Interestingly, expression of pluripotency markers showed
      different patterns between cell lines cultured in LIF or FGF2. SSEA4 was only
      expressed in FGF2-treated pig EGCs (FGF2-pEGCs), not LIF-treated pig EGCs (LIF
      pEGCs). Pluripotency genes were upregulated in FGF2-pEGCs, and germline markers
      were highly expressed, indicating that FGF2 supplements are more efficient in
      supporting the pluripotency of pEGCs. In conclusion, we verified that FGF2
      signaling plays an important role in reprogramming and maintaining pEGCs from
      fetal gonads.

PMID- 30204499
TI  - Sensory nerves mediate spontaneous behaviors in addition to inflammation in a
      murine model of psoriasis.
AB  - Psoriasis is characterized by keratinocyte hyperproliferation, erythema, as well
      as a form of pruritus, involving cutaneous discomfort. There is evidence from
      both clinical and murine models of psoriasis that chemical or surgical depletion
      of small-diameter sensory nerves/nociceptors benefits the condition, but the
      mechanisms are unclear. Hence, we aimed to understand the involvement of sensory
      nerve mediators with a murine model of psoriasis and associated spontaneous
      behaviors, indicative of cutaneous discomfort. We have established an Aldara
      model of psoriasis in mice and chemically depleted the small-diameter nociceptors
      in a selective manner. The spontaneous behaviors, in addition to the erythema and
      skin pathology, were markedly improved. Attenuated inflammation was associated
      with reduced dermal macrophage influx and production of reactive oxygen/nitrogen
      species (peroxynitrite and protein nitrosylation). Subsequently, this directly
      influenced observed behavioral responses. However, the blockade of common sensory
      neurogenic mechanisms for transient receptor potential (TRP)V1, TRPA1, and
      neuropeptides (substance P and calcitonin gene-related peptide) using genetic and
      pharmacological approaches inhibited the behaviors but not the inflammation.
      Thus, a critical role of the established sensory TRP-neuropeptide pathway in
      influencing cutaneous discomfort is revealed, indicating the therapeutic
      potential of agents that block that pathway. The ongoing inflammation is mediated
      by a distinct sensory pathway involving macrophage activation.-Kodji, X.,
      Arkless, K. L., Kee, Z., Cleary, S. J., Aubdool, A. A., Evans, E., Caton, P.,
      Pitchford, S. C., Brain, S. D. Sensory nerves mediate spontaneous behaviors in
      addition to inflammation in a murine model of psoriasis.

PMID- 30204500
TI  - Trophoblast VIP deficiency entails immune homeostasis loss and adverse pregnancy
      outcome in mice.
AB  - Immune homeostasis maintenance throughout pregnancy is critical for normal fetal
      development. Trophoblast cells differentiate into an invasive phenotype and
      contribute to the transformation of maternal arteries and the functional shaping
      of decidual leukocyte populations. Insufficient trophoblast invasion, inadequate
      vascular remodeling, and a loss of immunologic homeostasis are associated with
      pregnancy complications, such as preeclampsia and intrauterine growth
      restriction. Vasoactive intestinal peptide (VIP) is a pleiotropic neuropeptide
      synthetized in trophoblasts at the maternal-placental interface. It regulates the
      function of trophoblast cells and their interaction with decidual leukocytes. By
      means of a murine model of pregnancy in normal maternal background with VIP
      deficient trophoblast cells, here we demonstrate that trophoblast VIP is critical
      for trophoblast function: VIP gene haploinsufficiency results in lower matrix
      metalloproteinase 9 expression, and reduced migration and invasion capacities. A
      reduced number of regulatory T cells at the implantation sites along with a lower
      expression of proangiogenic and antiinflammatory markers were also observed.
      Findings detected in the implantation sites at early stages were followed by an
      abnormal placental structure and lower fetal weight. This effect was overcome by
      VIP treatment of the early pregnant mice. Our results support the relevance of
      trophoblast-synthesized VIP as a critical factor in vivo for trophoblast-cell
      function and immune homeostasis maintenance in mouse pregnancy.-Hauk, V., Vota,
      D., Gallino, L., Calo, G., Paparini, D., Merech, F., Ochoa, F., Zotta, E.,
      Ramhorst, R., Waschek, J., Leiros, C. P. Trophoblast VIP deficiency entails
      immune homeostasis loss and adverse pregnancy outcome in mice.

PMID- 30204502
TI  - Tissue-specific expression and post-transcriptional regulation of the ATPase
      inhibitory factor 1 (IF1) in human and mouse tissues.
AB  - The ATPase inhibitory factor 1 (IF1) is an intrinsically disordered protein that
      regulates the activity of the mitochondrial ATP synthase. Phosphorylation of S39
      in IF1 prevents it from binding to the enzyme and thus abolishes its inhibitory
      activity. Dysregulation of IF1 is linked to different human diseases, providing a
      relevant biomarker of cancer progression. However, the tissue content of IF1
      relative to the abundance of the ATP synthase is unknown. In this study, we
      characterized the tissue-specific expression of IF1 in human and mouse tissues
      and quantitated the content of IF1 and of ATP synthase. We found relevant
      differences in IF1 expression between human and mouse tissues and found that in
      high-energy-demanding tissues, the molar content of IF1 exceeds that of the ATP
      synthase. In these tissues, a fraction of IF1 is bound to the enzyme, and the
      other fraction is phosphorylated and hence is unable to bind the enzyme. Post
      transcriptional control accounts for most of the regulated expression of IF1,
      especially in mouse heart, where IF1 mRNA translation is repressed by the leucine
      rich pentatricopeptide repeat containing protein. Overall, these findings
      enlighten the cellular biology of IF1 and pave the way to development of
      additional models that address its role in pathophysiology.-Esparza-Molto, P. B.,
      Nuevo-Tapioles, C., Chamorro, M., Najera, L., Torresano, L., Santacatterina, F.,
      Cuezva, J. M. Tissue-specific expression and post-transcriptional regulation of
      the ATPase inhibitory factor 1 (IF1) in human and mouse tissues.

PMID- 30204501
TI  - The saturation degree of fatty acids and their derived acylcarnitines determines
      the direct effect of metabolically active thyroid hormones on insulin sensitivity
      in skeletal muscle cells.
AB  - Using differentiated rat L6 cells, we studied the direct effect of 3,5,3'-triiodo
      l-thyronine (T3) and 3,5-diiodo-l-thyronine (T2) on the response to insulin in
      presence of fatty acids with a varying degree of saturation. We found that T3 and
      T2 both invert the response to insulin by modulating Akt Ser473 phosphorylation
      in the presence of palmitate and oleate. Both hormones prevented palmitate
      induced insulin resistance, whereas increased insulin sensitivity in the presence
      of oleate was reduced, with normalization to (or, in the case of T3, even below)
      control levels. Both hormones effectively reduced intracellular acylcarnitine
      concentrations. Interestingly, insulin sensitization was lowered by incubation of
      the myotubes with relevant concentrations of palmitoylcarnitines (C16) and
      increased by oleylcarnitines and linoleylcarnitines (C18:1 and C18:2,
      respectively). The efficiency of mitochondrial respiration decreased in the order
      palmitate-oleate-linoleate; in the presence of palmitate, only T3 increased ATP
      synthesis-independent cellular respiration and mitochondrial respiratory complex
      activities. Both hormones modulated gene expression and enzyme activities related
      to insulin sensitivity, glucose metabolism, and lipid handling. Although T2 and
      T3 differentially regulated the expression of relevant genes involved in glucose
      metabolism, they equally stimulated related metabolic activities. T2 and T3
      differentially modulated mitochondrial fatty acid uptake and oxidation in the
      presence of each fatty acid. The results show that T2 and T3 both invert the
      fatty acid-induced response to insulin but through different mechanisms, and that
      the outcome depends on the degree of saturation of the fatty acids and their
      derived acylcarnitines.-Giacco, A., delli Paoli, G., Senese, R., Cioffi, F.,
      Silvestri, E., Moreno, M., Ruoppolo, M., Caterino, M., Costanzo, M., Lombardi,
      A., Goglia, F., Lanni, A., de Lange, P. The saturation degree of fatty acids and
      their derived acylcarnitines determines the direct effect of metabolically active
      thyroid hormones on insulin sensitivity in skeletal muscle cells.

PMID- 30204503
TI  - PERK regulates skeletal muscle mass and contractile function in adult mice.
AB  - Skeletal muscle mass is regulated by the coordinated activation of several
      anabolic and catabolic pathways. The endoplasmic reticulum (ER) is a major site
      of protein folding and a reservoir for calcium ions. Accretion of misfolded
      proteins or depletion in calcium concentration causes stress in the ER, which
      leads to the activation of a signaling network known as the unfolded protein
      response (UPR). In the present study, we investigated the role of the protein
      kinase R-like endoplasmic reticulum kinase (PERK) arm of the UPR in the
      regulation of skeletal muscle mass and function in naive conditions and in a
      mouse model of cancer cachexia. Our results demonstrate that the targeted
      inducible deletion of PERK reduces skeletal muscle mass, strength, and force
      production during isometric contractions. Deletion of PERK also causes a slow-to
      fast fiber type transition in skeletal muscle. Furthermore, short hairpin RNA
      mediated knockdown or pharmacologic inhibition of PERK leads to atrophy in
      cultured myotubes. While increasing the rate of protein synthesis, the targeted
      deletion of PERK leads to the increased expression of components of the ubiquitin
      proteasome system and autophagy in skeletal muscle. Ablation of PERK also
      increases the activation of calpains and deregulates the gene expression of the
      members of the FGF19 subfamily. Furthermore, the targeted deletion of PERK
      increases muscle wasting in Lewis lung carcinoma tumor-bearing mice. Our findings
      suggest that the PERK arm of the UPR is essential for the maintenance of skeletal
      muscle mass and function in adult mice.-Gallot, Y. S., Bohnert, K. R., Straughn,
      A. R., Xiong, G., Hindi, S. M., Kumar, A. PERK regulates skeletal muscle mass and
      contractile function in adult mice.

PMID- 30204505
TI  - Impact of IL-27p28 (rs153109) and TNF-alpha (rs1800629) Genetic Polymorphisms on
      the Progression of HCV Infection in Egyptian Patients.
AB  - BACKGROUND: Hepatitis C virus (HCV) is a universal health problem. HCV infection
      may proceed to liver fibrosis, cirrhosis, and eventually hepatocellular carcinoma
      (HCC). The latest is the third leading global cause of cancer-related mortality.
      Cytokines including IL-27 and TNF-alpha play a major role as a link between
      innate and adaptive immunity which in turn deduct the outcome of HCV infection.
      AIM: The present study examined the role of both (-964 A/G) single-nucleotide
      polymorphism (SNP) of IL-27p28 rs153109 and (-308 G/A) SNP of TNF-alpha rs1800629
      on the progression of HCV infection in genotype 4a infected patients. PATIENTS
      AND METHODS: The patients enrolled in the study were divided into three main
      groups group I: 38 fibrotic patients, group II: 51 cirrhotic patients, and
      finally group III: 29 HCC patients. Sixteen healthy volunteers were used as
      controls. IL-27p28 rs153109 and TNF-alpha rs1800629 genotyping were performed
      using polymerase chain reaction-restriction fragment length polymorphism assay.
      RESULTS: There was no statistically significant difference between the studied
      groups regarding the IL-27p28 genotypes. However, TNF-alpha (-308) studied
      polymorphism showed a significant difference between the HCC and fibrosis group
      (p = 0.00), and also between the cirrhosis and fibrosis group (p = 0.031)
      revealing that AA genotype is the genotype of risk. Furthermore, the association
      found between allele frequencies of two studied SNPs and the four studied groups
      were non-significant. CONCLUSION: TNF-alpha rs1800629 polymorphism is a potential
      genetic-susceptibility factor for HCV related cirrhosis and HCC progression.

PMID- 30204504
TI  - Elobixibat for the Treatment of Constipation.
AB  - INTRODUCTION: Chronic idiopathic constipation (CC) is highly prevalent worldwide.
      A subset of patients with CC have reduced fecal (and by inference, intra-colonic)
      bile acids (BA). Elobixibat, a locally-acting ileal bile acid transporter (IBAT)
      inhibitor, leads to increased BA delivery to the colon and represents a new class
      of treatment for CC. BAs accelerate colonic transit and increase colonic
      secretion. Therefore, IBAT inhibitors have potential to treat patients with CC.
      Areas covered: Rationale for IBAT inhibitor in therapeutics, and preclinical and
      clinical pharmacology of elobixibat: In vitro, elobixibat is a highly potent,
      selective IBAT inhibitor. In humans, elobixibat accelerated colonic transit. In
      phase 2A, 2B and 3 studies in CC, elobixibat was efficacious, well tolerated and
      safe. An open-label, phase 3 trial (52 weeks) confirmed the safety of elobixibat.
      Elobixibat reduces LDL cholesterol, increases serum GLP-1, and has potential in
      metabolic syndrome. Expert commentary: Uniquely among current treatments of CC,
      elobixibat stimulates both motor and secretory functions in the colon. These dual
      effects suggest that, when approved, elobixibat may be a first-line choice for
      constipation associated with colonic BA deficiency and a second-line treatment
      for all patients with CC and constipation-predominant irritable bowel syndrome.
      Further studies are required to confirm efficacy for relief of CC. Once approved,
      elobixibat will likely become a second-line choice for treatment of CC.

PMID- 30204506
TI  - The Difference in Neuromuscular Fatigue and Workload During Competition and
      Training in Elite Cricketers.
AB  - PURPOSE: To firstly, assess changes in neuromuscular function via alterations in
      the countermovement jump strategy, after training and two forms of competition.
      Secondly, to compare the relationship between workloads and fatigue in seam
      bowlers and non-seam bowlers. METHODS: Twenty-two professional cricketers'
      neuromuscular function was assessed at baseline, immediately post and +24 h post
      training, as well as after multi-day and one-day cricket events. In addition,
      perceptual (rating of perceived exertion; RPE and soreness) measures and external
      loads (Player LoadTM, number of sprints, total distance, overs) were monitored
      across all formats. RESULTS: Seam bowlers covered more distance, completed more
      sprints and had a higher RPE in training (P < 0.05), without any difference in
      soreness compared to non-seam bowlers. Interestingly, compared to seam bowlers,
      the non-seam bowlers peak force decreased post-24 h compared to baseline only in
      one-day cricket (95% CI 2.1 -110.0 N; P < 0.04). There were no pre-post training
      or match differences in jump height or alterations in jump strategy (P > 0.05).
      Seam bowlers increased their peak jumping force from baseline to immediately post
      training or game (95% CI 28.8 - 132.4 N; P < 0.01) but decreased between post
      cricket to +24 h (95% CI 48.89 - 148.0 N; P < 0.001). CONCLUSION: Seam bowlers
      were more accustomed to high workloads compared to non-seamers and, thus, more
      fatigue resistant. Changes in jump height or strategy do not appear to be
      effective methods of assessing fatigue in professional crickets. More common
      metrics, such as peak force, are more sensitive.

PMID- 30204507
TI  - Effects of Concentric and Eccentric Strength Training on Fatigue Induced by
      Concentric and Eccentric Exercise.
AB  - PURPOSE: This study compared the concentric and eccentric training effects on
      fatigue induced by eccentric and concentric protocols. METHODS: Twenty-two men
      and women (22 +/- 3.6 years) were assigned to concentric (GCON, n=11) or
      eccentric training (GECC, n=11). The concentric (CON) and eccentric (ECC)
      protocols were composed of 4 sets of 20 knee extension/flexion repetitions. Force
      losses were analysed by comparing 10 repetitions' mean torques during the
      protocols and verifying the maximal voluntary contraction (MVC) and rate of
      torque development (RTD) before and after the protocols. Muscle damage was
      assessed using echo intensity (EI) of the vastus lateralis 48 hours after the
      protocols. Training consisted of 6 weeks of isokinetic exercise at 60 degrees .s
      1 (concentric or eccentric) twice weekly. RESULTS: Before training, both
      protocols resulted in dynamic and isometric force losses in GCON and GECC
      (P<0.01), but the magnitude was greater after the CON protocol than after the ECC
      protocol (P<0.001). After training, both GCON and GECC showed similar force
      decreases during the CON and ECC protocols (P<0.01), and these changes were not
      different from the pre-training decreases. Regarding MVC after training, GECC
      showed lower force decreases than GCON after ECC exercise (-13.7 vs. -22.3%,
      respectively, P<0.05), whereas GCON showed lower MVC decreases after CON exercise
      compared with pre-training (-29.2%, P<0.05). RTD losses were similar after the
      protocols before and after the training regimens. No changes in EI were observed
      after the protocols before and after training. CONCLUSIONS: Both interventions
      resulted in similar force decreases during fatigue protocols when compared with
      those associated with pre-training.

PMID- 30204508
TI  - Opioid and Benzodiazepine Relative Use in Breast Cancer Patients Before, During,
      and After Curative Chemotherapy.

PMID- 30204509
TI  - Load-Velocity Relationship in National Paralympic Powerlifters: A Case Study.
AB  - PURPOSE: This study examined the relationships between different loading
      intensities and movement velocities in the bench-press exercise (BP) in
      Paralympic powerlifters. METHODS: Seventeen National Paralympic powerlifters
      performed maximum dynamic strength tests to determine their BP one-repetition
      maximum (1RM) in a Smith-machine device. A linear position transducer was used to
      measure the movement velocity over a comprehensive range of loads. Linear
      regression analysis was performed to establish the relationships between the
      different bar-velocities and the distinct percentages of 1RM (%1RM). RESULTS:
      Overall, the correlations between bar-velocities and %1RM were strong over the
      entire range of loads (R2 values ranged from 0.80 to 0.91), but the precision of
      the predictive equations (expressed as mean differences [%] between actual and
      predicted 1RM values) were higher at heavier loading intensities (~20% for loads
      <= 70% 1RM, and ~5% for loads >= 70%1RM). In addition, it seems that these very
      strong athletes (e.g., 1RM relative in the BP = 2.22 +/- 0.36 kg.kg-1, for male
      participants) perform BP 1RM assessments at lower velocities than those
      previously reported in the literature. CONCLUSIONS: The load-velocity
      relationship was strong and consistent in Paralympic powerlifters, especially at
      higher loads (>= 70% 1RM). Therefore, Paralympic coaches can use the predictive
      equations and the reference values provided here to determine and monitor the BP
      loading intensity in National Paralympic powerlifters.

PMID- 30204510
TI  - The influence of voice quality and multi-talker babble noise on sentence
      processing and recall performance in school children using cochlear implant
      and/or hearing aids.
AB  - PURPOSE: This study examines the influence of voice quality and multi-talker
      babble noise on processing and storage performance in a working memory task
      performed by children using cochlear implants (CI) and/or hearing aids (HA).
      METHODS: Twenty-three children with a hearing impairment using CI and/or HA
      participated. Age range was between 6 and 13 years. The Competing Language
      Processing Task (CLPT) was assessed in three listening conditions; a typical
      voice presented in quiet, a dysphonic voice in quiet, and a typical voice in
      multi-talker babble noise (signal-to-noise ratio +10 dB). Being a dual task, the
      CLPT consists of a sentence processing component and a recall component. The
      recall component constitutes the measure of working memory capacity (WMC). Higher
      level executive function was assessed using Elithorn?s mazes. RESULTS: The
      results showed that the dysphonic voice did not affect performance in the
      processing component or performance in the recall component. Multi-talker babble
      noise decreased performance in the recall component but not in the processing
      component. Higher-level executive function was not significantly related to
      performance in any component. CONCLUSIONS: The findings indicate that multi
      talker babble noise, but not a dysphonic voice quality, seems to put strain on
      WMC in children using CI and/or HA. Abbreviations CLPT competing language
      processing task ISTS international speech test signal SLP speech and language
      pathologists WMC working memory capacity.

PMID- 30204511
TI  - Evaluation of an Integrated Rescue Task Force Model for Active Threat Response.
AB  - OBJECTIVE: An integrated response to active threat events is essential to saving
      lives. Coordination of law enforcement officer (LEO) and emergency medical
      services (EMS) roles requires joint training, as maximizing survival is a shared
      responsibility. We sought to evaluate the performance of an integrated LEO-EMS
      Rescue Task Force (RTF) response to a simulated active shooter incident utilizing
      objective performance measures. METHODS: Following prior didactic training, we
      conducted a series of evaluation scenarios for EMS providers and patrol officers
      in our urban/suburban advanced life support EMS system (pop. 1,000,000). The
      scenario-tested command staff, LEOs tasked with neutralizing an active shooter
      threat, and two RTFs of LEOs and EMS providers each tasked with triage and
      treatment of 11 simulated casualties scattered over 2 office building floors
      totaling 13,000 square feet. Trained evaluators recorded performance on 30
      objective data elements related to LEO-EMS operations/communication, time
      intervals, and trauma care. Data were analyzed using descriptive statistics and t
      tests for between group comparisons. RESULTS: Over 18 days, 69 scenario events
      evaluated 388 EMS providers and 468 LEOs. Overall median (90th percentile) times
      in minutes from dispatch were: unified command established 4.1 (5.5), RTF
      assembled 9.4 (13.5), first victim contact 11.9 (16.5), first victim to internal
      casualty collection point (CCP) 16.6 (20.8), all victims ready for evacuation
      21.6 (26.0). Life-saving interventions included tourniquet placed: 96% (95% CI 92
      99) and LEO placed tourniquet: 88% (79-94). Clinical delays included
      inappropriate chest decompression: 4% (2-9) and unnecessary initial treatment:
      17% (12-25). Correct operational actions included communication with LEO to
      ensure EMS was safe to treat: 70% (61-77) and appropriate CCP selection: 84% (74
      91). Incorrect operational actions included failure to maintain protective LEO
      EMS formation: 49% (45-62) and inappropriate single patient evacuation: 20% (14
      28). Limitations included the lack of a pre-training control group for this novel
      program. CONCLUSIONS: We described the performance of an integrated LEO-EMS
      Rescue Task Force response to a simulated active shooter event in a large city.
      In general, clinical care was appropriate while operational targets can be
      improved. Objective measurement of response goals may be used for benchmarking
      and performance improvement for active threat events.

PMID- 30204512
TI  - Determining the Relationship Between Internal Load Markers and Non-Contact
      Injuries in Young Elite Soccer Players.
AB  - PURPOSE: To examine the association and predictive ability of internal load
      markers with regards to non-contact injuries in young elite soccer players.
      METHODS: Twenty-two soccer players (18.6 +/- .6 years) who competed in the
      Spanish U19 League participated in the study. During a full season, non-contact
      injuries were recorded and, using session rating of perceived exertion (s-RPE),
      internal weekly load (sum of load of all training sessions and matches for each
      week) and acute:chronic workload ratio (typically, acute = current week and
      chronic = rolling 4 week average) were calculated. A Generalized Estimating
      Equation analysis was used to examine association of weekly and acute:chronic
      load ratio markers with a non-contact injury in the subsequent week. Load
      variables were also analyzed for predictive ability with Receiver Operating
      Characteristic (ROC) curve and area under the curve (AUC). RESULTS: No
      association was found for weekly load (CI 1.00, .99 to 1.00) and acute:chronic
      load ratio (CI .16, .01 to 1.84) with respect to injury occurrence. In addition,
      the analyzed load markers showed poor ability to predict injury occurrence
      (AUC<.50). CONCLUSIONS: The results of this study suggest that internal load
      markers are not associated with non-contact injuries in young soccer players and
      present poor predictive capacity with regards to the latter.

PMID- 30204513
TI  - Identifying Patterns of Delirium in Hospitalized Patients on Dexamethasone Using
      a Chart Abstraction Tool.
AB  - Delirium is a neuropsychiatric syndrome that can occur in hospitalized patients,
      including in palliative care settings. The aim of this study is to describe
      patterns of delirium in patients receiving dexamethasone at the request of an
      inpatient palliative consultation team by using a modified chart abstraction
      tool. This retrospective study analyzed patterns of delirium development in adult
      hospitalized patients receiving opioids for cancer-related pain and initiated on
      dexamethasone with recommendation from the palliative care team. Primary end
      point described patterns of delirium, and the study secondarily analyzed source
      delirium documentation, Glasgow Coma Scale score, Richmond Agitation-Sedation
      Scale score, and Eastern Cooperative Oncology Group Performance pre- and post
      dexamethasone administration. A total 59 patients were included in this
      retrospective chart review. There was no difference in delirium rate during the
      pre- and post-dexamethasone periods (n = 35 and 31, respectively; P = .62). There
      also were no significant differences in mental status, agitation, or functional
      status before or after dexamethasone, although data were limited by electronic
      health record incompleteness. Evidence of delirium was most commonly documented
      in physician notes (n = 58, 71%). The findings showed that incidence and severity
      of delirium were not impacted after patients were started on dexamethasone as
      recommended by an inpatient palliative team, although data were limited.

PMID- 30204514
TI  - The Reproducibility and External Validity of a Modified Rugby League Movement
      Simulation Protocol for Interchange Players.
AB  - PURPOSE: The study assessed the reliability and external validity of a rugby
      league movement simulation protocol for interchange players that was adapted to
      include physical contact between participants. METHODS: Eighteen rugby players
      performed two trials of a modified rugby league movement simulation protocol for
      interchange players (RLMSP-i), seven days apart. The simulation was conduced
      outdoors on artificial turf with movement speeds controlled using an audio
      signal. Micro-technology was used to measure locomotive and accelerometer (i.e.
      PlayerLoadTM) metrics for both bouts (~23 min each) alongside heart rate and RPE.
      RESULTS: Reported for each bout, total distance (102 +/- 3 and 101 +/- 3 m.min
      1), low-speed distance (77 +/- 3 and 79 +/- 4 m.min-1), high-speed distance (25
      +/- 3 and 22 +/- 4 m.min-1), PlayerLoadTM (10 +/- 1 and 10 +/- 1 AU.min-1),
      PlayerLoadTM slow (3.2 +/- 0.6 and 3.2 +/- 0.6 AU.min-1), PlayerLoadTM 2D (6.0 +/
      0.9 and 5.7 +/- 0.8 AU.min-1) and heart rate (86 +/- 5 and 84 +/- 6 %HR max)
      were similar to match play. The coefficient of variation (%CV) for locomotive
      metrics ranged from 1.3 to 14.4%, accelerometer CV% 4.4 to 10.0%, and internal
      load 4.8 to 13.7%. All variables presented a CV% less than the calculated
      moderate change during one or both bouts of the simulation except high-speed
      distance (m.min-1), %HRpeak and RPE (AU). CONCLUSION: The modified RLMSP-i offers
      a reliable simulation to investigate influences of training and nutrition
      interventions on the movement and collision activities of rugby league
      interchange players.

PMID- 30204515
TI  - Development of a Pediatric Goal-Centered Upper Limb Spasticity Home Exercise
      Therapy Program for Use in a Phase-III Trial of Abobotulinumtoxina (Dysport(r)).
AB  - AIMS: To create a standardized home exercise therapy program that could be
      implemented by international sites to provide a consistent level of therapeutic
      intervention for pediatric patients participating in an ongoing Phase-III,
      randomized, controlled trial of repeat abobotulinumtoxinA injections for
      pediatric upper limb spasticity (NCT02106351). METHODS: Physical therapists,
      occupational therapists, and medical doctors worked collaboratively to design an
      exercise therapy program to be implemented in the home setting. In this article,
      we describe the development process and the finalized program that is currently
      being used in the Phase-III trial. RESULTS: The final program is presented as a
      "toolbox" for therapists, and includes a standardized step-wise process for
      choosing the most appropriate exercises and functional activities to achieve the
      agreed treatment goals of each abobotulinumtoxinA injection. The core toolbox
      includes: a clear protocol for clinicians, information sheets, signature of
      commitment forms, exercise score charts, and the library of exercises and
      functional activities that therapists choose from to aid the patient in achieving
      their treatment goals. CONCLUSIONS: Implementation of this home therapy program
      provides a standardized background of good practice against which to test the
      efficacy of abobotulinumtoxinA. Preliminary data show that the program is readily
      accepted by patients and their families.

PMID- 30204517
TI  - Presleep Casein Protein Ingestion: Acceleration of Functional Recovery in
      Professional Soccer Players.
AB  - PURPOSE: This study examined whether consuming casein protein (CP) before sleep
      would enhance recovery after a night-time soccer match in professional players.
      METHODS: In a randomized, crossover design, ten professional soccer players from
      the reserve squad of a team in the highest tier of English soccer consumed 40 g
      of CP or 40 g of carbohydrates (CON) 30 min pre-sleep after a soccer match (kick
      off 19:00). To assess recovery, countermovement jump (CMJ) height, reactive
      strength index (RSI), muscle soreness (MS), and the adapted Brief Assessment of
      Mood Questionnaire (BAM+) were measured before, 12, 36 and 60 h after each match.
      Dietary intake across the testing period was also recorded. RESULTS: There were
      unclear differences in external load in the matches and dietary intake between
      CON and CP. CP had a most likely and likely beneficial effect on CMJ recovery at
      12 and 36 h post-match (CP -1.6; +/-1.2% vs. CON -6.6; +/-1.7%; -4.1; +/-2.3% vs.
      -0.4; +/-1.1%, respectively). RSI recovery was most likely enhanced with CP at 12
      and 36 h post-match and muscle soreness, as measured with a visual analogue scale
      (mm), was most likely greater in CON vs. CP at 12 h post (72; +/-17 vs. 42; +/-20
      mm). BAM+ was possibly lower in CON at 36 h post but unaffected at other time
      points. CONCLUSIONS: Pre-sleep CP accelerates functional recovery in professional
      soccer players and therefore provides a practical means of attenuating
      performance deficits in the days after a match.

PMID- 30204516
TI  - Caffeine and Sprint Cycling Performance: Effects of Torque Factor and Sprint
      Duration.
AB  - PURPOSE: The aim of this study was to investigate the influence of torque factor
      and sprint duration on the effects of caffeine on sprint cycling performance.
      METHODS: Using a counterbalanced, randomized, double-blind, placebo-controlled
      design, 13 men completed nine trials. In Trial 1, participants completed a series
      of 6 s sprints at increasing torque factors, to determine the torque factor, for
      each individual, which elicited the highest (TOPTIMAL) peak power output (PPO).
      The remaining trials involved all combinations of torque factor (0.8 N?m?kg-1
      versus TOPTIMAL), sprint duration (10 s versus 30 s), and supplementation
      (caffeine [5 mg?kg-1] versus placebo). RESULTS: There was a significant effect of
      torque factor on PPO, with higher values at TOPTIMAL (mean difference: 168 W; 95%
      likely range: 142 - 195 W). There was also a significant effect of sprint
      duration on PPO, with higher values in 10 s sprints (mean difference: 52 W; 95%
      likely range: 18 - 86 W). However, there was no effect of supplementation on PPO
      (p = 0.056). Nevertheless, there was a significant torque factor * sprint
      duration * supplement interaction (p = 0.036), with post hoc tests revealing that
      caffeine produced a higher PPO (mean difference: 76 W; 95% likely range: 19 - 133
      W) when the sprint duration was 10 s and the torque factor was TOPTIMAL.
      CONCLUSIONS: The results of this study show that when torque factor and sprint
      duration are optimized, to allow participants to express their highest PPO, there
      is a clear effect of caffeine on sprinting performance.

PMID- 30204518
TI  - Improvement of Kinetic, Kinematic, and Qualitative Performance Variables of the
      Power Clean With the Hook Grip.
AB  - PURPOSE: The power clean (PC) and other weightlifting movements are commonly used
      in the development of muscular power. However, there is a paucity of research
      examining the use of the hook-grip (HG) in weightlifting performance. Therefore
      the purpose of this study was to compare one repetition maximum (1RM) and
      kinetic, kinematic, and qualitative variables across a range of loads (75-100%)
      during PC performance with a HG and a closed-grip (CG). METHODS: Eleven well
      trained males (PC 1RM = 113.4 +/- 15.9 kg, 1.34 x body mass) with at least three
      months of HG experience volunteered to participate. Following a familiarization
      session, 1RM testing with the HG and CG were completed five to seven days apart
      in a randomized order. Barbell kinetic and kinematic variables were recorded via
      a force platform and dual linear position transducer system. RESULTS: All
      subjects had a greater 1RM with the HG when compared to the CG (p < 0.001, ES =
      0.43). Peak velocity (ES = 0.41-0.70), peak power (ES = 0.43-0.61), peak force
      (ES = 0.50-0.57) and catch height (ES = 0.40-0.96) were significantly greater (p
      < 0.05) when utilizing the HG at all, or most of the submaximal intensities.
      Additionally, subjects reported significantly greater perceptions of grip
      security, power and technical competency at submaximal, but not maximal loads.
      CONCLUSIONS: Therefore, athletes and coaches who implement weightlifting
      movements in their physical preparation should adopt the HG where possible.
      Furthermore, researchers and sports scientists should control and report the grip
      type used when performing weightlifting-type movements.

PMID- 30204519
TI  - Youth's Perspective of Responsibility: Exploration of a Construct for Measurement
      with Youth with Developmental Disabilities.
AB  - AIMS: There is a need to develop self-reports that measure youth's responsibility
      for major life tasks. We examined if the Pediatric Evaluation of Disability
      Inventory-Computer Adaptive Test's (PEDI-CAT) operationalization of
      responsibility is salient to youth with developmental disabilities (DD). The PEDI
      CAT defines responsibility as, "the extent to which the young person...take[s]
      control over organizing and managing major life tasks." METHODS: During six focus
      groups (n = 43), youth generated examples of behaviors and actions that
      demonstrated responsibility. Data were coded as "responsibility" or "discrete
      skills" per PEDI-CAT definitions. We reviewed examples in both categories and
      compared and contrasted how youth described responsibility. RESULTS: Youth's
      descriptions of responsibility aligned with the PEDI-CAT's responsibility
      construct 42.75% of the time. In these instances, youth perceived themselves as
      causal agents who had to make decisions and self-regulate to manage and organize
      major life tasks. Otherwise, youth described themselves as causal agents who
      adhered to rules, social norms, and expectations of others during the execution
      of discrete skills. CONCLUSIONS: Youth perceive themselves as responsible, causal
      agents during both the coordination and management of major life tasks and during
      the execution of discrete skills. As this is not aligned with the PEDI-CAT's
      operationalization of responsibility, there is a need to further explore youth's
      perceptions of responsibility prior to developing a self-report.

PMID- 30204520
TI  - Effects of Plyometric and Directional Training on Physical Fitness Parameters in
      Youth Soccer Players.
AB  - PURPOSE: The aim of this study is to investigate whether the combination of a
      soccer training session, plyometric training (PT) and change of direction (COD)
      exercises would enhance soccer ability to a greater extent than training on its
      own in youth soccer players. METHODS: Thirty-one youth players participated in
      this study (age 12+/-0.8 years). Players were randomly separated into 2 groups:
      control group (CG, n=14) and intervention group (INTG) which performed extra PT
      and COD exercises (INTG, n=17). The duration of the training program was 6 weeks.
      Sprint 10m, 30m, countermovement jump (CMJ), squat jump (SJ), long jump (LJ),
      multiple 5-bound (5MB), T-test, and YO-YO intermitted endurance test 1 (YYIET1)
      were measured pre and post of the training program. RESULTS: The performance in
      acceleration, T-test and LJ improved in both groups (P=0.03, P=0.002 and P=0.001,
      respectively). SJ performance increased in INTG (15.2 %, P=0.003) and slightly
      decreased in CG (P=0.003). The performances of the 2 groups differed
      significantly in SJ and LJ (P=0.003 and P=0.038, respectively). CONCLUSIONS: This
      study supports that a short-term combined program of PT and COD exercises can
      improve jumping ability, acceleration, and endurance parameters in youth soccer
      players. The small training effect could be explained when taking into account
      the level of the participants, the duration of the program and the low volume of
      COD exercises that were used.

PMID- 30204521
TI  - Current and emerging treatment options for autoimmune hemolytic anemia.
AB  - INTRODUCTION: Autoimmune hemolytic anemia (AIHA) is a heterogeneous disease
      mainly due to autoantibody-mediated destruction of erythrocytes but also involves
      complement activation, dysregulation of cellular and innate immunity, and
      defective bone marrow compensatory response. Several drugs targeting these
      mechanisms are under development in addition to standard therapies. Areas
      covered: The following targeted therapies are illustrated: drugs acting on CD20
      (rituximab, alone or in association with bendamustine and fludarabine) and CD52
      (alemtuzumab), B cell receptor and proteasome inhibitors (ibrutinib, bortezomib),
      complement inhibitors (eculizumab, BIVV009, APL-2), and other drugs targeting T
      lymphocytes (subcutaneous IL-2, belimumab, and mTOR inhibitors), IgG driven
      extravascular hemolysis (fostamatinib), and bone marrow activity (luspatercept).
      Expert opinion: Although AIHA is considered benign and often easy to treat,
      chronic/refractory cases represent a challenge even for experts in the field.
      Bone marrow biopsy is fundamental to assess one of the main mechanisms
      contributing to AIHA severity, i.e. inadequate compensation, along with lymphoid
      infiltrate, the presence of fibrosis or dyserythropoiesis. The latter may give
      hints for targeted therapies (either B or T cell directed) and for new
      immunomodulatory drugs. Future studies on the genomic landscape in AIHA will
      further help in designing the best choice, sequence and/or combination of
      targeted therapies.

PMID- 30204522
TI  - Approaches to the prevention of postnatal depression and anxiety - a review of
      the literature.
AB  - INTRODUCTION: Poor maternal mental health during the perinatal period has been
      shown to have potentially long-lasting effects for mother and child. In
      recognition of this, maternal mental health is receiving increased attention from
      political and healthcare organizations, with a growing focus on preventing the
      onset of common mental health disorders. OBJECTIVE: The objective for this review
      is to provide an update of randomized controlled trials examining the use of
      interventions targeted to prevent the onset of postnatal depression and anxiety
      in nondiagnostic populations with universal or selected samples. METHODS: A total
      of four databases, EBSCO Host, Science Direct, Scopus, and Web of Science,
      incorporating PsychINFO were searched and papers selected according to clearly
      specified inclusion criteria. A large Health Technology review was published in
      2016, for which the final search was conducted in December 2012. Therefore
      inclusion criteria were studies published from January 2013 onwards, available in
      English language, had a focus on prevention of postnatal maternal depression and
      anxiety, and used psychological interventions. Drug intervention trials were
      excluded. FINDINGS: 12 studies were identified as examining antenatal or
      postnatal intervention trials with an aim of preventing maternal postnatal
      depression and/or anxiety. There continues to be limited evidence to recommend
      specific prevention strategies for universal samples without further testing.
      There is evidence to suggest the use of rational-emotive behavioral therapy in an
      antenatal sample may have some utility, and the use of psychotherapy-based
      interventions in a postnatal setting is also supported although both require
      further investigation. Additionally, there is a need to gather information on
      acceptability, as many trials were hindered by poor adherence to interventions
      and high attrition that were otherwise unexplained.

PMID- 30204524
TI  - Enhanced Anti-Leukemic Effects through Induction of Immunomodulating
      Microenvironment by Blocking CXCR4 and PD-L1 in an AML Mouse Model.
AB  - Previously, we found that dual therapy by the CXCR4 inhibitor Plerixafor and
      cytosine arabinoside (Ara-C) effectively eradicated leukemia cells and
      concurrently activated immune cells in acute myeloid leukemia (AML). To reveal
      the significance of programmed death-ligand1 (PD-L1) in AML and as a strategic
      approach, we investigated the anti-leukemic effect of a triple combinational
      therapy by utilizing Plerixafor and anti-PD-L1 in combination with chemotherapy
      in an AML mouse model. We examined leukemic myeloid blast cells in multiple
      organs after the successive treatment with Ara-C, Plerixafor, and anti-PD-L1. The
      results showed that noticeable benefits of triple combinational therapy for
      eradication of myeloid blast cells in vivo with prolonged survival rates. The
      frequencies of regulatory T cells (Tregs), monocytic-myeloid-derived suppressor
      cells (M-MDSCs), and granulocytic-myeloid-derived suppressor cells (G-MDSCs), in
      the peripheral blood of leukemic mice were consistently decreased, even when mice
      were sacrificed alive at D + 26 after completion of the triple combinational
      therapy, compared to the other subgroups. These findings imply that the
      modulation by the triple combinational therapy may lead to more efficient
      leukemic myeloid blast cell ablation through the suppression of Tregs or M-MDSCs
      and G-MDSCs in AML. Although Plerixafor and PD-L1 antagonist do not have a direct
      anti-leukemic role, our results provide some clues and guidelines to develop
      clinically therapeutic strategies for chemotherapy-resistant patients by the
      modulation of leukemic microenvironments.

PMID- 30204523
TI  - Higher vs. Lower Intensity Strength Training Taper: Effects on Neuromuscular
      Performance.
AB  - PURPOSE: To investigate the effects of strength training tapers of different
      intensities, but equal volume reductions, on neuromuscular performance. METHODS:
      Eleven strength-trained males (21.3+/-3.3 years, 92.3+/-17.6 kg, relative 1RM
      deadlift 1.9+/-0.2 times bodyweight) completed a crossover study. Specifically,
      two four-week strength training blocks were followed by a taper week with reduced
      volume (~70%) involving either an increased (5.9%) or decreased (-8.5%)
      intensity. Testing occurred pre-training (T1), post-training (T2), and post-taper
      (T3). Salivary testosterone and cortisol, plasma creatine kinase, a daily
      analysis of life demands in athletes questionnaire, countermovement jump (CMJ),
      isometric mid-thigh pull (IMTP) and bench press (IBP) were measured. RESULTS: CMJ
      height improved significantly over time (p<0.001), with significant increases
      from T1 (38.0+/-5.5 cm) to both T2 (39.3+/-5.3 cm; p=0.010) and T3 (40.0+/-5.3
      cm; p=0.001), and from T2 to T3 (p=0.002). CMJ flight-time: contraction-time
      increased significantly over time (p=0.004), with significant increases from T1
      (0.747+/-0.162) to T2 (0.791+/-0.163; p=0.012). IMTP relative peak force improved
      significantly over time (p=0.033), with significant increases from T1 (34.7+/-5.0
      N/kg) to T2 (35.9+/-4.8 N/kg; p=0.013). No significant changes were found between
      tapers. However, the higher intensity taper produced small ES increases at T3 vs.
      T1 for IMTP relative peak force, CMJ height and flight-time: contraction-time,
      while the lower intensity taper only produced small ES improvements at T3 vs. T1
      for CMJ height. CONCLUSIONS: A strength training taper with volume reductions had
      a positive effect on power, with a tendency for the higher intensity taper to
      produce more favourable changes in strength and power.

PMID- 30204525
TI  - Development of a novel training system for laparoscopic inguinal hernia repair.
AB  - BACKGROUND: Laparoscopic inguinal hernia repair is considered technically
      difficult. Although a simulation-based curriculum has been developed to help
      trainees, access to simulation training outside North America is limited. This
      study aimed to develop an educational system for the transabdominal preperitoneal
      (TAPP) approach based on the TAPP checklist, an assessment tool we had developed
      and validated earlier. MATERIAL AND METHODS: Consensus within the TAPP education
      working group consisting of local TAPP experts, hernia experts and a surgical
      educator to develop educational tools and the educational system based on the
      TAPP checklist. The system was piloted in several institutes, and participants
      were surveyed on its efficacy. RESULTS: We systematically developed an
      educational video and training manual explaining each item of the TAPP checklist
      and conveying basic knowledge of the procedure. We integrated the training tool
      with evaluation and feedback to develop an educational system. In a pilot study,
      seven trainees at five hospitals were trained using this system and found it very
      useful for mastering the TAPP procedure. CONCLUSIONS: We have developed a
      training system for TAPP procedure and successfully implemented it in several
      hospitals. Further research will focus on the educational value of this tool.

PMID- 30204526
TI  - Clinical trial of the D.E.L.P.H.I.N. speech treatment for children and
      adolescents who stutter.
AB  - PURPOSE: The present trial investigated the D.E.L.P.H.I.N. (Deblockierungsimpuls,
      Entspannung, Logopadie, Phonetik, Hor-Wahrnehmungstraining, Intensitat, nasaler
      Schwingungsakzent) speech treatment for children and adolescents who stutter, an
      approach using fluency shaping with an intensive time schedule and group
      sessions. METHODS: Participants were 42 male and 14 female persons who stuttered
      with a median age of 13.0 years. Participants and their parents completed the
      strength and difficulties questionnaire at the beginning of the therapy and 1
      year later. Participants completed the Speech Questionnaire, an instrument to
      measure the impact of stuttering, twice before and twice after completing the
      therapy. The stuttering rate and mean length of the three longest stuttering
      events were studied four times in videos of interviews, reading texts and three
      telephone calls. Outcomes are reported for the 56 children and young adults who
      stuttered and who completed D.E.L.P.H.I.N. The main analysis was performed using
      linear mixed models. RESULTS: Quality of life as measured in the Strength and
      Difficulties Questionnaire (SDQ) - filled in by the participants/their parents -
      increased significantly from before the start of the therapy to 1 year after
      completion of the therapy. The subjective rating of the impact of stuttering also
      improved significantly. The stuttering rate and mean length of the longest
      stuttering event decreased significantly for all three modes from pre-treatment
      to 12 months post-treatment. CONCLUSIONS: After D.E.L.P.H.I.N., a significant
      improvement of the relevant endpoints quality of life, impact of stuttering, and
      severity of stuttering is observed.

PMID- 30204527
TI  - Laparoscopic hysterectomy in chronic renal failure patients with abnormal uterine
      bleeding.
AB  - BACKGROUND: Chronic renal failure (CRF) in women is frequently accompanied by
      endocrine disturbances leading to abnormal uterine bleeding (AUB). Recurrence of
      AUB is the most significant problem following current treatment approaches.
      Laparoscopic hysterectomy (LH) might be taken into consideration for patients who
      no longer want to preserve their fertility; however, these patients are in high
      risk groups for minimally invasive surgery. Our goal was to determine whether LH
      is a good option for the treatment of AUB in patients with CRF when the
      associated risks are carefully managed. MATERIAL AND METHODS: This study included
      five patients who underwent LH for abnormal uterine bleeding between 2013 and
      2016. Enhanced perioperative management and techniques were adopted to allow LH
      with minimized risks to the patient. RESULTS: All patients underwent LH
      successfully, without organ failure, heavy infection or abdominal cavity bleeding
      during the perioperative period. Operation times ranged from 95 to 152 min (mean
      time 117.6 min). The mean intraoperative blood loss was 24 ml. No recurrence was
      observed during the 18 months follow-up period. CONCLUSION: For CRF patients with
      AUB who no longer want to preserve their fertility, hysterectomy may be a better
      option, not only to permanently resolve the problem, but also to remove the risk
      of future uterine lesions. The improved protocols minimized the specific risks of
      laparoscopy arising from the patient's coexisting medical problems, making LH a
      feasible treatment approach in CRF patients with AUB.

PMID- 30204528
TI  - Validity of Session Rating of Perceived Exertion Assessed via the CR100(r) Scale
      to Track Internal Load in Elite Youth Football Players.
AB  - PURPOSE: To assess the convergent validity of the Borg CR100(r) scale to track
      internal training load (TL) in youth football players. METHODS: Nineteen youth
      football players (age 15 +/- 1 y, height 175.9 +/- 12.3 cm, body mass 69 +/- 15.4
      kg) were monitored for 27 sessions, including training and games. Internal
      training load was assessed via session rating of perceived exertion (sRPE) and
      two heart rate (HR)-based methods; Banister's training impulse (TRIMP) and
      Edwards' TL. The correlations between sRPE and HR-based TL, the differences in
      individual player intercepts and slopes, and the differences between types of
      sessions (training vs. games) were assessed using a general linear mixed model
      with magnitude-based inferences. RESULTS: Correlations between sRPE and
      Banister's TRIMP were very large at overall group level (r=0.77, 90% confidence
      limits (CL) 0.72 to 0.80), and individual level (range 0.70 - 0.95). Correlations
      between sRPE and Edwards' TL were very large at overall group level (r=0.84, 90%
      CL 0.82 to 0.86), and large to very large at individual level (range 0.64 -
      0.93). A very likely small difference was found in the comparison between games
      and training sessions for the relationship between sRPE and Banister's TRIMP.
      CONCLUSIONS: The Borg CR100(r) scale is a valid method for monitoring training
      load in youth football players.

PMID- 30204529
TI  - Inter-Unit Reliability and Effect of Data Processing Methods of Global
      Positioning Systems.
AB  - PURPOSE: To establish the inter-unit reliability of a range of Global Positioning
      System (GPS)-derived movement indicators, determine the variation between
      manufacturers, and investigate the difference between software-derived and raw
      data. METHODS: A range of movement variables were obtained from 27 GPS units from
      three manufacturers (GPSports EVO; 10 Hz, n = 10: STATSports Apex; 10 Hz, n = 10:
      and Catapult S5; 10 Hz, n = 7) that measured the same team-sports simulation
      session while positioned on a sled. The inter-unit reliability was determined
      using the coefficient of variation (CV; %) and 90% confidence limits (CL),
      whereas between manufacturer comparisons, and also comparisons of software versus
      raw processed data were established using standardized effect sizes (ES) and 90%
      CL. RESULTS: The inter-unit reliability for both software and raw processed data
      ranged from good to poor (CV = 0.2%; +/-1.5% to 78.2%; +/-1.5%), with distance,
      speed, and maximal speed exhibiting the best reliability. There were substantial
      differences between manufacturers, particularly for threshold-based acceleration
      and deceleration variables (ES; +/-90% CL [-2.0%; +/-0.1 to 1.9%; +/-0.1%]), and
      there were substantial differences between data processing methods for a range of
      movement indicators. CONCLUSIONS: The inter-unit reliability of most movement
      indicators were deemed as good regardless of processing method, suggesting that
      practitioners can have confidence within systems. Standardized data processing
      methods are recommended, due to the large differences between data outputs from
      various manufacturer-derived software.

PMID- 30204530
TI  - The Influence of Pleasure and Attentional Focus on Performance and Pacing
      Strategies in Elite Individual Time Trials.
AB  - : Recent psychophysiological models of endurance performance explained that
      pacing strategies and exercise intensity regulation influence cyclists' ability
      to produce high mean power output (PO) during time-trial. However, the
      relationships between these pacing strategies and psychological parameters of the
      athletes remain unknown. PURPOSE: The aims of this study were to 1) determine the
      impact of pacing strategies on cyclists' mean PO during an elite time-trial
      championship and 2) identify the relationships between these pacing strategies
      and psychological parameters. METHODS: Mean power output, projected frontal area,
      attentional focus and pleasure were recorded for nine male cyclists during an
      official ITT national championship. Pacing regulations were quantified from PO
      using the new Exposure Variation Analysis (EVA), which determines times spent at
      adapted PO (APO) and inaccurate PO (IPO) for optimal constant pacing strategy.
      Relationships between mean PO, times spent at APO and IPO and psychological
      variables were analysed. RESULTS: Significant relationships were found between
      mean PO and EVA pacing parameters (r2 from 0.56 to 0.86; p > 0.05). Time spent at
      IPO was negatively related to pleasure during the ITT (r = -0.746; p = 0.016).
      Conversely, time spent at APO was significantly related to cyclists' attentional
      focus (r = 0.827; p = 0.006). CONCLUSIONS: Mean PO during elite ITT is directly
      related to the athletes' ability to optimally regulate pace throughout the event.
      This pacing regulation is influenced by attentional focus and pleasure,
      underlining that coaches and athletes should devote greater attention to these
      psychological parameters in order to improve their performances.

PMID- 30204532
TI  - Powerful or Powerless? Children's, Parents', and Occupational Therapists'
      Perceptions of Powered Mobility.
AB  - AIM: In Quebec, Canada, the prevalence of children using powered mobility (PM) is
      not reflective of evidence supporting its use and for achieving developmental
      milestones. The aim of this study was to explore the perceptions of four key
      stakeholder groups in a metropolitan area regarding daily use, barriers,
      facilitators, and clinical practice associated with use of PM. METHODS: Using
      convenience sampling, semi-structured qualitative interviews were conducted with
      children (n = 6), parents (n = 2), rehabilitation center occupational therapists
      (OTs; n = 4), and special needs school-based OTs (n = 6). Drawings were used as a
      supplemental data collection strategy with children. Interviews were audio
      recorded and transcribed verbatim to conduct thematic analysis. RESULTS: Three
      overarching themes were identified: (1) "A sense of liberty, except...",
      highlighting environmental obstacles reducing social participation; (2) "A
      necessity, for better or for worse," covering benefits and drawbacks of PM; and
      (3) "First choice versus last resort," raising clinical differences related to
      provision, assessment, and training. CONCLUSIONS: Stakeholders' perceptions
      illustrated benefits of PM, yet use is contingent on the physical, institutional,
      and societal environments, leading stakeholders to feel both powerful and
      powerless as users, parents, or clinicians.

PMID- 30204531
TI  - Postpartum psychological distress after emergency team response during
      childbirth.
AB  - PURPOSE: To evaluate the feasibility and acceptability of a protocol determining
      the relationship between emergency team response (ETR) during childbirth and
      acute stress disorder (ASD) and post-traumatic stress disorder (PTSD) symptoms.
      METHODS: In a prospective, observational, cohort design, women experiencing ETR
      during childbirth were approached and recruited on postpartum day-1 and followed
      for six weeks. Demographics, obstetric and birth characteristics, ASD scores and
      PTSD scores (by Impact of Events Scale, IES and PCL-civilian) were recorded.
      Recruitment and retention rates were recorded, and scores were compared to women
      who did not experience ETR. RESULTS: Three hundred sixty-nine were approached and
      249 were enrolled (67.5% recruitment rate). One hundred twenty-five completed all
      procedures (50.2% retention). Twenty experienced ETR (3.5% event rate), 12
      enrolled (60.0% recruitment rate) and 8 completed the study (66.7% retention).
      The ETR group had higher PCL and IES scores (PCL: ETR median 12, non-ETR median
      2, p = .08; IES: ETR median 22.5, non-ETR median 20, p = .08). ASD scores were
      similar between groups. CONCLUSIONS: Methodology investigating the link between
      ETR and postpartum psychological distress is feasible and acceptable. A
      relationship between ETR and PTSD symptoms appears to exist, with ETR being
      associated with higher PTSD scores compared to non-ETR childbirths. Methods that
      incorporate awareness of the unique concerns of vulnerable populations are
      needed.

PMID- 30204533
TI  - Identification of G-Quadruplex-Binding Inhibitors of Myc Expression through
      Affinity Selection-Mass Spectrometry.
AB  - The Myc oncogene is overexpressed in many cancers, yet targeting it for cancer
      therapy has remained elusive. One strategy for inhibition of Myc expression is
      through stabilization of the G-quadruplex (G4), a G-rich DNA secondary structure
      found within the Myc promoter; stabilization of G4s has been shown to halt
      transcription of downstream gene products. Here we used the Automated Ligand
      Identification System (ALIS), an affinity selection-mass spectrometry method, to
      identify compounds that bind to the Myc G4 out of a pool of compounds that had
      previously been shown to inhibit Myc expression in a reporter screen. Using an
      ALIS-based screen, we identified hits that bound to the Myc G4, a small subset of
      which bound preferentially relative to G4s from the promoters of five other
      genes. To determine functionality and specificity of the Myc G4-binding compounds
      in cell-based assays, we compared inhibition of Myc expression in cells with and
      without Myc G4 regulation. Several compounds inhibited Myc expression only in the
      Myc G4-containing line, and one compound was verified to function through Myc G4
      binding. Our study demonstrates that ALIS can be used to identify selective
      nucleic acid-binding compounds from phenotypic screen hits, increasing the pool
      of drug targets beyond proteins.

PMID- 30204534
TI  - Development of High-Throughput Screening Assays for Inhibitors of ETS
      Transcription Factors.
AB  - ETS transcription factors from the ERG and ETV1/4/5 subfamilies are overexpressed
      in the majority of prostate cancer patients and contribute to disease
      progression. Here, we have developed two in vitro assays for the interaction of
      ETS transcription factors with DNA that are amenable to high-throughput
      screening. Using ETS1 as a model, we applied these assays to screen 110 compounds
      derived from a high-throughput virtual screen. We found that the use of lower
      affinity DNA binding sequences, similar to those that ERG and ETV1 bind to in
      prostate cells, allowed for higher inhibition from many of these test compounds.
      Further pilot experiments demonstrated that the in vitro assays are robust for
      ERG, ETV1, and ETV5, three of the ETS transcription factors that are
      overexpressed in prostate cancer.

PMID- 30204535
TI  - Patient education in physiotherapy in total hip arthroplasty (THA) - The
      perspective of physiotherapists.
AB  - BACKGROUND AND PURPOSE: There is limited knowledge about patients' and
      physiotherapists' perceptions of patient education in physiotherapy in hip
      arthroplasty. The aim of this study was to describe physiotherapists' conceptions
      of the patient education in physiotherapy needed by patients undergoing total hip
      arthroplasty. METHODS: The data for this qualitative study were collected using
      group and individual semi-structured interviews. Seven physiotherapists were
      interviewed. The research data were analyzed using a phenomenographic method.
      RESULTS: Three categories of patient education in physiotherapy in hip
      arthroplasty were produced and the categories formed a hierarchy. The narrowest
      descriptive category was Schematic physiotherapy complying with the protocol.
      Identifying individual rehabilitation needs was the second category, and the
      third, widest category was Coaching home rehabilitation. The differences between
      the categories were described in four themes: 1) Moving; 2) Exercising; 3)
      Interaction in relation to patient; and 4) Health care system. CONCLUSION:
      According to the results, patient education in physiotherapy optimally aims to
      identify patients' individual rehabilitation needs, advice on coping at home and
      especially helping patients to be prepared for and capable of long rehabilitation
      for which they are themselves responsible. These findings resulting from
      descriptive categories can be utilized in developing education methods and
      physiotherapists' competence in patient education.

PMID- 30204536
TI  - Feasibility of Implementing the Patient-Reported Outcomes Version of the Common
      Terminology Criteria for Adverse Events in a Multicenter Trial: NCCTG N1048.
AB  - Purpose The US National Cancer Institute (NCI) Patient-Reported Outcomes version
      of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) was developed
      to enable patient reporting of symptomatic adverse events in oncology clinical
      research. This study was designed to assess the feasibility and resource
      requirements associated with implementing PRO-CTCAE in a multicenter trial.
      Methods Patients with locally advanced rectal cancer enrolled in the National
      Cancer Institute-sponsored North Central Cancer Treatment Group (Alliance)
      Preoperative Radiation or Selective Preoperative Radiation and Evaluation before
      Chemotherapy and Total Mesorectal Excision trial were asked to self-report 30 PRO
      CTCAE items weekly from home during preoperative therapy, and every 6 months
      after surgery, via either the Web or an automated telephone system. If
      participants did not self-report within 3 days, a central coordinator called them
      to complete the items. Compliance was defined as the proportion of participants
      who completed PRO-CTCAE assessments at expected time points. Results The
      prespecified PRO-CTCAE analysis was conducted after the 500th patient completed
      the 6-month follow-up (median age, 56 years; 33% female; 12% nonwhite; 43% high
      school education or less; 5% Spanish speaking), across 165 sites. PRO-CTCAE was
      reported by participants at 4,491 of 4,882 expected preoperative time points
      (92.0% compliance), of which 3,771 (77.2%) were self-reported by participants and
      720 (14.7%) were collected via central coordinator backup. Compliance at 6-month
      post-treatment follow-up was 333 of 468 (71.2%), with 122 (26.1%) via backup.
      Site research associates spent a median of 15 minutes on PRO-CTCAE work for each
      patient visit. Work by a central coordinator required a 50% time commitment.
      Conclusion Home-based reporting of PRO-CTCAE in a multicenter trial is feasible,
      with high patient compliance and low site administrative requirements. PRO-CTCAE
      data capture is improved through centralized backup calls.

PMID- 30204537
TI  - Breast Cancer Screening: Women's Attitudes and Beliefs in Light of Updated United
      States Preventive Services Task Force and American Cancer Society Guidelines.
AB  - BACKGROUND: In recently updated breast cancer screening guidelines, the American
      Cancer Society (ACS) and United States Preventive Services Task Force (USPSTF)
      recommended increasing mammography screening intervals for various age groups. In
      addition, ACS does not recommend clinical breast examination (CBE) for routine
      screening among average-risk women. Our study explores women's attitudes
      regarding screening mammography and CBE and evaluates the impact of the updated
      USPSTF and ACS guidelines on these attitudes. MATERIALS AND METHODS: Six hundred
      fourteen patients presenting to Mayo Clinic, Arizona and Minnesota, in July 2016
      completed a self-administered survey, which included a summary of the updated
      guidelines. RESULTS: A majority of the 555 women who fit the inclusion criteria
      reported that CBE and mammogram are useful in detecting breast cancer and should
      be performed annually, and 51% of participants were unaware of the updated
      guidelines. Before reviewing the guidelines, 77% believed yearly CBE and 76%
      believed yearly mammogram was needed for routine screening. After reviewing the
      guidelines, the percentage of women who planned to continue with yearly CBE and
      mammogram decreased significantly to 61% and 64%, respectively (p < 0.001 and p <
      0.001). Nearly half the participants (48%) believed the most influential reason
      for the guideline change was to decrease healthcare spending. CONCLUSION: Breast
      cancer screening is well received among patients, and a majority of surveyed
      women were unaware of recent guideline changes. After reviewing the guidelines,
      there was a significant downward shift in intended screening frequency, although
      the majority still planned to undergo annual screening. Informing women about
      updated evidence-based guidelines may influence their knowledge, preferences, and
      opinions.

PMID- 30204538
TI  - Aerially guided leak detection and repair: A pilot field study for evaluating the
      potential of methane emission detection and cost-effectiveness.
AB  - Novel aerial methane (CH4) detection technologies were used in this study to
      identify anomalously high-emitting oil and gas (O&G) facilities and to guide
      ground-based "leak detection and repair" (LDAR) teams. This approach has the
      potential to enable a rapid and effective inspection of O&G facilities under
      voluntary or regulatory LDAR programs to identify and mitigate anomalously large
      CH4 emissions from a disproportionately small number of facilities. This is the
      first study of which the authors are aware to deploy, evaluate, and compare the
      CH4 detection volumes and cost-effectiveness of aerially guided and purely ground
      based LDAR techniques. Two aerial methods, the Kairos Aerospace infrared CH4
      column imaging and the Scientific Aviation in situ aircraft CH4 mole fraction
      measurements, were tested during a 2-week period in the Fayetteville Shale region
      contemporaneously with conventional ground-based LDAR. We show that aerially
      guided LDAR can be at least as cost-effective as ground-based LDAR, but several
      variable parameters were identified that strongly affect cost-effectiveness and
      which require field research and improvements beyond this pilot study. These
      parameters include (i) CH4 minimum dectectable limit of aerial technologies, (ii)
      emission rate size distributions of sources, (iii) remote distinction of fixable
      versus nonfixable CH4 sources ("leaks" vs. CH4 emissions occurring by design),
      and (iv) the fraction of fixable sources to total CH4 emissions. Suggestions for
      future study design are provided. Implications: Mitigation of methane leaks from
      existing oil and gas operations currently relies on on-site inspections of all
      applicable facilities at a prescribed frequency. This approach is labor- and cost
      intensive, especially because a majority of oil and gas-related methane emissions
      originate from a disproportionately small number of facilities and components. We
      show for the first time in real-world conditions how aerial methane measurements
      can identify anomalously high-emitting facilities to enable a rapid, focused, and
      directed ground inspection of these facilities. The aerially guided approach can
      be more cost-effective than current practices, especially when implementing the
      aircraft deployment improvements discussed here.

PMID- 30204539
TI  - Characteristics of particle emissions and their atmospheric dilution during co
      combustion of coal and wood pellets in a large combined heat and power plant.
AB  - Coal combustion is one of the most significant anthropogenic CO2 and air
      pollution sources globally. This paper studies the atmospheric emissions of a
      power plant fuelled with a mixture of industrial pellets (10.5%) and coal
      (89.5%). Based on the stack measurements, the solid particle number emission,
      which was dominated by sub-200 nm particles, was 3.4*1011 MJ-1 for the fuel
      mixture when electrostatic precipitator (ESP) was cleaning the flue gas. The
      emission factor was 50 mg MJ-1 for particulate mass and 11 740 ng MJ-1 for the
      black carbon with the ESP. In the normal operation situation of the power plant,
      i.e., including the flue-gas desulphurisation and fabric filters (FGD and FF),
      the particle number emission factor was 1.7*108 MJ-1, particulate mass emission
      factor 2 mg MJ-1 and black carbon emission factor 14 ng MJ-1. Transmission
      electron microscopy (TEM) analysis supported the particle number size
      distribution measurement in terms of particle size and the black carbon
      concentration. The TEM images of the particles showed variability of the particle
      sizes, morphologies and chemical compositions. The atmospheric measurements,
      conducted in the flue-gas plume, showed that the flue-gas dilutes closed to
      background concentrations in 200 sec. However, an increase in particle number
      concentration was observed when the flue gas aged. This increase in particle
      number concentration was interpret as formation of new particles in the
      atmosphere. In general, the study highlights the importance of detailed particle
      measurements when utilizing new fuels in existing power plants. Implications: CO2
      emissions of energy production decrease when substituting coal with biofuels. The
      effects of fuels changes on particle emission characteristics have not been
      studied comprehensively. In this study conducted for a real-scale power plant, co
      combustion of wood pellets and coal caused elevated black carbon emissions.
      However, it was beneficial from the total particle number and particulate mass
      emission point of view. Flue-gas cleaning can significantly decrease the
      pollutant concentrations but also changes the characteristics of emitted
      particles. Atmospheric measurements implicated that the new particle formation in
      the atmospheric flue-gas plume should be taken into account when evaluating all
      effects of fuel changes." Are implication statements part of the manuscript?

PMID- 30204540
TI  - Survival After Exercise-Related Sudden Cardiac Arrest in Young Athletes: Can We
      Do Better?
AB  - BACKGROUND: Sudden cardiac arrest (SCA) is the leading cause of death in young
      athletes during sports. HYPOTHESIS: Survival after SCA in young athletes is
      variable. STUDY DESIGN: Prospective, active surveillance study. LEVEL OF
      EVIDENCE: Level 3. METHODS: From July 1, 2014, to June 30, 2016, exercise-related
      SCA in competitive young athletes was identified through a systematic search of
      traditional and social media sources, direct reporting to the National Center for
      Catastrophic Sports Injury Research, searching of the National Collegiate
      Athletic Association Resolutions List, regular communication with national and
      state high school athletic associations, and review of cases in the Parent Heart
      Watch database. RESULTS: A total of 132 cases were identified during the 2-year
      study period (mean patient age, 16 years; age range, 11-27 years; 84% male; 51%
      white non-Hispanic/Latino, 30% black/African American, and 11% white
      Hispanic/Latino). High school athletes accounted for 78 (59%) cases, with 28
      (21%) in middle school and 15 (11%) in college athletes. Overall survival was 48%
      (95% CI, 40%-57%; 64 survivors, 68 deaths). Survival was similar in male versus
      female athletes but higher in white non-Hispanic/Latino (40/67; 60%) versus
      black/African American (13/39; 33%) athletes (difference, 27%; 95% CI, 7%-45%; P
      = 0.008) and white non-Hispanic/Latino versus all minority (18/59; 31%) athletes
      (difference, 29%; 95% CI, 13%-46%; P = 0.001). Basketball accounted for 30% of
      cases, followed by football (25%), track/cross-country (12%), and soccer (11%).
      The majority (93%) of cases were witnessed. If a certified athletic trainer was
      on-site and involved in the resuscitation, 83% of athletes survived. If an on
      site automated external defibrillator was used in the resuscitation, 89% of
      athletes survived. CONCLUSION: Exercise-related SCA in young, competitive
      athletes is typically witnessed, providing an opportunity for rapid
      resuscitation. Additional research is needed to identify factors that affect
      survival in different athlete populations. CLINICAL RELEVANCE: Public access
      defibrillator programs should be universal in schools and youth sporting venues
      and have the potential to increase survival after SCA in young athletes.

PMID- 30204541
TI  - Keeping it Simple: Impact of a Restrictive Antibiotic Policy for Ventilator
      Associated Pneumonia in Trauma Patients on Incidence and Sensitivities of
      Causative Pathogens.
AB  - BACKGROUND: An integral part of ventilator-associated pneumonia (VAP) therapy is
      the appropriate choice of empiric antibiotics. Our previous experience
      demonstrated adherence to an empiric therapy pathway was associated with only
      modest changes in organisms causing VAP. The purpose of the current study was to
      evaluate the impact of a restrictive antibiotic policy for VAP in trauma patients
      on the incidence and sensitivities of causative pathogens since the previous
      study. PATIENTS AND METHODS: Patients with VAP diagnosed on bronchoalveolar
      lavage since the previous study were stratified by age, gender, mechanism of
      injury, and injury severity. All patients received empiric antibiotics based on
      duration of intensive care unit (ICU) stay using a unit-specific pathway. The
      incidence and sensitivities of causative pathogens in the current study were
      documented. The adequacy of the VAP pathway was evaluated for all VAP episodes.
      The current study was then compared with the previous study. RESULTS: Over a 10
      year period, 1,474 episodes of VAP were diagnosed with 2,387 causative pathogens
      isolated. Overall incidence of gram-positive and gram-negative VAP pathogens was
      unchanged between the study periods. The current study experienced an increase in
      the incidence of Staphylococcus aureus (23% vs. 17%, p = 0.001) and methicillin
      resistant Staphylococcus aureus (10% vs. 6%, p = 0.002) compared with the
      previous study. The pathway for empiric antibiotics resulted in adequate empiric
      coverage in 85% of VAP episodes, which was improved compared with the previous
      study (76%, p = 0.024). Furthermore, despite the increased incidence of early
      methicillin-resistant Staphylococcus aureus (MRSA) VAP, adequacy of the pathway
      improved for both the early period (91% vs. 86%, p = 0.001) as well as the late
      period (86% vs. 63%, p < 0.001) in the current study compared with the previous
      study. CONCLUSIONS: A comprehensive protocol for the diagnosis and management of
      VAP, along with antibiotic stewardship, can prevent the development of bacterial
      resistance to empiric therapy.

PMID- 30204542
TI  - Milk and Plasma Lutein and Zeaxanthin Concentrations in Chinese Breast-Feeding
      Mother-Infant Dyads With Healthy Maternal Fruit and Vegetable Intake.
AB  - OBJECTIVES: While others have reported that milk from coastal Chinese women
      contains high levels of lutein and zeaxanthin, no research has determined the
      corresponding infant plasma response. Whether infant plasma levels increase
      commensurately provides important guidance for supplementation of these
      increasingly intriguing carotenoids in breast-feeding mothers and formula-fed
      infants. METHODS: Fifty-six mother-infant pairs with a maternal diet rich in
      eggs, green leafy vegetables, and fruit were enrolled between 6 and 16 weeks of
      lactation. Milk samples and blood samples from both the mother and infant were
      collected at entry. Maternal 3-day dietary records and a second milk sample were
      collected 1 to 3 weeks later. RESULTS: Mean milk lutein concentrations in samples
      1 and 2 were 6.5 and 7.7 MUg/dL (range 1-22.5 MUg/dL), and for zeaxanthin, 1.6
      and 1.7 MUg/dL (range 1-5.9 MUg/dL). Lutein concentrations in infant plasma (18.2
      MUg/dL) were similar to those in maternal plasma (21.6 MUg/dL); zeaxanthin was
      lower than lutein in both maternal (3.1 MUg/dL) and infant (2.9 MUg/dL) plasma.
      Infant and maternal mean plasma lutein and zeaxanthin concentrations were higher
      than those in both milk samples 1 and 2 (lutein, 6.9 and 8.2 MUg/dL; zeaxanthin,
      1.9 and 2.0 MUg/dL). Infant plasma lutein and zeaxanthin concentrations
      positively correlated with those in milk sample 1 (lutein, r2 = 0.15, p = 0.004;
      zeaxanthin, r2 = 0.21, p < 0.001). CONCLUSIONS: Together, these results reveal
      that high milk concentrations of lutein and zeaxanthin driven by healthy maternal
      intakes of xanthophyll rich foods are associated with high infant plasma
      concentrations. These findings will be useful for determining appropriate lutein
      fortification strategies. Clinical Study.gov registration number: NCT01669655.

PMID- 30204544
TI  - Provider Perspectives on Quality Payment Programs Targeting Diabetes in Primary
      Care Settings.
AB  - Public and private insurers increasingly use quality payment programs as a tool
      to improve quality of care in primary care settings. However, little is known
      about primary care providers' perspectives on whether and how quality payment
      programs improve diabetes quality of care. In this qualitative study, the authors
      conducted semi-structured interviews and focus groups with 23 providers from
      March to June 2015. Transcripts were analyzed to identify key themes using the
      immersion-crystallization method. Almost all of the providers believed that
      insurers play a meaningful role in improving quality of care for diabetes
      patients. Most thought that insurers' efforts are more effective when channeled
      through providers and delivery systems rather than directed at patients.
      Providers generally believed that quality payment programs have had a positive
      impact on quality of diabetes care, although provider views were not evidence
      based. Providers in practices in which quality payment programs were believed to
      have had a positive impact stated that the programs provided financial incentives
      and resources for improved population health management systems and additional
      staff. Conversely, most providers did not believe that quality payment programs
      have had any impact via direct financial incentives to individual physicians. A
      few providers were skeptical about the impact of quality payment programs and
      noted negative consequences that they had observed. Providers recommended
      strategies to improve quality payment programs (eg, refine quality measures,
      provide regular feedback on quality and costs) and additional strategies that
      insurers could consider to address provider- and patient-level barriers to high
      quality diabetes care.

PMID- 30204543
TI  - Top Ten Tips Palliative Care Clinicians Should Know About Parkinson's Disease and
      Related Disorders.
AB  - Parkinson's disease (PD) affects 1%-2% of individuals older than 60 years and is
      the 14th leading cause of death in the United States. People with PD, across all
      stages of the disease, suffer from a significant symptom burden that includes
      many nonmotor symptoms (such as depression, fatigue, pain, and dementia), and
      most will ultimately die from complications of this degenerative and incurable
      illness. Even at diagnosis, a palliative care (PC) approach can help the patient
      adjust to his or her diagnosis and maintain an optimal quality of life. We
      brought together a team of PD and PC experts to assemble practical tips for the
      care of people with PD. The "Top 10" format emphasizes the most relevant issues
      to enable PC clinicians to provide optimal care for those suffering with this
      complex neurodegenerative disease.

PMID- 30204546
TI  - Dose Intensification Improves the Outcome of Ewing Sarcoma.

PMID- 30204547
TI  - Kinetics of systemic invasion and latent and incubation periods of Tomato severe
      rugose virus and Tomato chlorosis virus in single and co-infections in tomato
      plants.
AB  - Tomato severe rugose virus (ToSRV) and tomato chlorosis virus (ToCV) are among
      the major viruses that affect tomato (Solanum lycopersicum) development and yield
      in Brazil. ToSRV and ToCV are transmitted in a persistent circulative and semi
      persistent manner, respectively, by the whitefly Bemisia tabaci Middle East-Asia
      Minor 1 (MEAM1), considered the main vector of these viruses. In this study, the
      kinetics of systemic invasion and the latent and incubation periods of ToSRV and
      ToCV were evaluated in singly- and doubly-infected tomato plants. Both viruses
      moved systemically into tomato plants as early as one day after inoculation. The
      mean ToCV latent periods in single and co-infections with ToSRV were 13 and 11
      days, respectively, while incubation periods in single and co-infections were, on
      average, 30 and 31 days, respectively. For ToSRV, the mean latent period was 7
      days in single infections and 6 days in co-infections with ToCV. Incubation
      periods were, on average, 18 and 17 days in single and co-infections,
      respectively. As latent periods for both viruses were shorter than their
      respective incubation periods, field-infected tomato plants may act as sources of
      inocula soon after infection and before onset of symptoms.

PMID- 30204550
TI  - Becoming Accountable for Delivery of High-Value Care: Preparing for the End of
      "Do More, Earn More".

PMID- 30204549
TI  - Antibiotics versus No Antibiotics for the Treatment of Acute Uncomplicated
      Diverticulitis: Review of the Evidence and Future Directions.
AB  - BACKGROUND: Acute diverticulitis occurs in 25% of individuals with diverticular
      disease and is associated with significant morbidity and mortality rates. Disease
      severity is classified as uncomplicated or complicated, with the latter including
      perforation, fistula, obstruction, or distant abscess. Uncomplicated
      diverticulitis often improves without surgery or invasive therapies.
      Administration of antibiotics is a standard of care for treatment of acute
      uncomplicated diverticulitis. However, recent data suggest antibiotics do not
      influence outcomes significantly. To address these conflicting approaches, the
      Surgical Infection Society hosted an Update Symposium at its 37th Annual Meeting
      examining the role of antibiotics in the treatment of acute uncomplicated
      diverticulitis. Here, we provide a synopsis of the symposium's findings and a
      brief review of recent prospective and randomized clinical trials on the topic.
      METHODS: A search of Embase, MEDLINE, and the Cochrane Library was performed for
      prospective series and randomized clinical trials published between January 1,
      2010, and January 1, 2018, comparing outcomes of antibiotic versus no antibiotic
      therapy for acute uncomplicated diverticulitis. RESULTS: We identified two single
      center prospective series and two randomized clinical trials comparing outcomes
      for patients with acute uncomplicated diverticulitis treated with antibiotics
      versus no antibiotics. CONCLUSION: Current evidence does not support
      administration of antibiotics to improve outcomes in carefully selected healthy
      patients with acute uncomplicated left-sided diverticulitis. Further studies
      should help identify specific subpopulations of patients who would derive benefit
      from antibiotic therapy and help define appropriate antibiotic regimens and
      treatment durations that minimize cost, adverse effects, and risk of anti
      microbial resistance.

PMID- 30204548
TI  - Is the Use of Refrigerated Fixed Combination of Dorzolamide 2%-Timolol 0.5%
      (COSOPT) Associated with Less Ocular Discomfort: A Pilot Study.
AB  - PURPOSE: To test the hypothesis that the use of refrigerated fixed combination of
      dorzolamide 2% plus timolol 0.5% solution (COSOPT(r)) is associated with less
      ocular discomfort compared with the use of this solution kept at room
      temperature. METHODS: In this prospective comparative study, 30 primary open
      angle patients and 30 healthy subjects filled in the questionnaire on symptoms
      (Ocular Surface Disease Index) and subjective stinging feeling scale (1-10), at
      the start of study and 30 days after continuous use of refrigerated fixed
      combination or placebo eye drops. Results were processed by applying the methods
      of descriptive (arithmetical mean, standard deviation) and analytical statistics
      for evaluation of significance of the difference (Student's t-test). RESULTS:
      Ocular discomfort parameters were significantly lower after the use of
      refrigerated fixed combination of dorzolamide 2% plus timolol 0.5% solution (t
      test, P < 0.0001). Breakup time, Schirmer 1 test, and intraocular pressure values
      did not differ. CONCLUSIONS: The use of refrigerated fixed combination of
      dorzolamide 2% plus timolol 0.5% (COSOPT) solution is associated with less ocular
      discomfort than the use of the same fixed combination at room temperature.

PMID- 30204551
TI  - Gender as an Independent Risk Factor for the Components of Metabolic Syndrome
      Among Individuals Within the Normal Range of Body Mass Index.
AB  - BACKGROUND: Overweight and obesity are more common in men than in women. This
      explains the higher prevalence of risk factors for metabolic syndrome (MetS)
      found in men. We aimed to assess whether gender, per se, might be an independent
      risk factor for the components of MetS in a large cohort of subjects within the
      normal range of body mass index (BMI). MATERIALS AND METHODS: Cross-sectional
      analysis was carried out on 9976 men and women, aged 18 to 70 years, with a BMI
      between 18.5 and 25.0 kg/m2 attending a screening center in Israel between the
      years 2000 and 2014. RESULTS: Mean (SD) age of the study sample was 43.3 (9.6)
      years, 54.5% were men. Prevalence of MetS components in men and women was
      hypertension 5.3% and 3.0%, impaired fasting glucose (IFG) 18.1% and 7.9%,
      diabetes mellitus (DM) 2.4% and 1.3%, high triglyceride levels 17.7% and 9.4%,
      and low high-density lipoprotein (HDL) cholesterol levels 13.6% and 17.0%,
      respectively, P < 0.001 for all. Increased waist circumference was <1% in both
      genders. Multivariate analysis showed male gender to be an independent risk
      factor for IFG [odds ratio (OR) 2.43, 95% confidence interval (CI) 2.12-2.79],
      hypertriglyceridemia (OR 1.86, 95% CI 1.63-2.12), DM (OR 1.80, 95% CI 1.29-2.50),
      and hypertension (OR 1.46, 95% CI 1.16-1.83) but not for low HDL levels (OR 0.59,
      95% CI 0.52-0.67). CONCLUSION: This study, on a cross-sectional sample of
      subjects with a normal BMI, showed male gender to be an independent risk factor
      for all components of the MetS, apart from the low HDL risk factor that was found
      to be higher in women.

PMID- 30204552
TI  - "Bath Salt" Use and Beliefs about Use among Electronic Dance Music Attendees.
AB  - Use of synthetic cathinones ("bath salts") has been associated with tens of
      thousands of emergency department visits. Few surveys, however, query use.
      Research on "bath salt" use is needed, especially in high-risk populations, to
      inform prevention and harm reduction efforts. A total of 933 adults (ages 18-40)
      were surveyed entering electronic dance music (EDM) parties in New York City in
      2017. Lifetime use of 22 different synthetic cathinones was queried, and
      agreement with four statements about "bath salts" was also assessed. Prevalence
      and correlates of self-reported "bath salt" use was examined as well as
      correlates of beliefs about "bath salts." An estimated 3.5% of EDM attendees have
      knowingly used "bath salts." Almost half (46.7%) believe "bath salts" are more
      harmful than MDMA, 30.1% believe "bath salts" have turned users into cannibals,
      30.0% believe "bath salts" are sometimes found in Molly, and 14.9% believe they
      might have unknowingly used "bath salts." Males, those earning <$500 per week,
      and those with a college degree were at higher risk for use. Believing "bath
      salts" have turned users into cannibals, however, was protective against use.
      Findings suggest the need for more accurate information (e.g., regarding drug
      effects) on this large and heterogeneous group of compounds.

PMID- 30204553
TI  - Lower plasma protein C activity is associated with early myocardial necrosis and
      no-reflow phenomenon in patients with ST elevation myocardial infarction.
AB  - BACKGROUND: Activity of protein C has important role in the development of early
      necrosis and no-reflow phenomenon in patients with ST-segment elevation
      myocardial infarction (STEMI) after successful primary percutaneous coronary
      intervention (pPCI). METHODS: We examined association between plasma activity of
      protein C, antithrombin, coagulation factors II, VII, VIII and fibrinogen to
      early formation of new Q-waves (myocardial necrosis) before pPCI and early ST
      segment resolution (microcirculatory reperfusion) after pPCI in patients with
      acute STEMI. According to ischaemic time, patients were considered as early or
      late presenters. 12-lead ECG was analysed for the presence of new Q-wave at
      admission and for significant ST-segment resolution 60 minutes after primary PCI.
      RESULTS: In early presenters' group, protein C activity was significantly lower
      in patients who did not achieve significant ST-segment resolution after pPCI
      compared to patients who did (1.11 IU/L vs. 0.99 IU/L, p = .006) and in patients
      who had new Q-waves compared to group who had not (1.04 UI/l vs. 1.11 IU/L, p =
      .038). There was significant negative correlation between protein C activity and
      maximal CK-MB levels (R2 = 0.06, p = .009) and BNP levels (R2 = 0.109, p = .003)
      and significant positive correlation between protein C activity with LVEF (R2 =
      0.065, constant = 33.940, b = 11.968, p = .007) in early STEMI presenters. There
      were no differences between the activity of other examined haemostasis factors.
      CONCLUSION: Therefore we concluded that STEMI patients with early myocardial
      necrosis and no-reflow phenomenon after pPCI have lower activity of plasma
      protein C levels.

PMID- 30204554
TI  - The PPARgamma Agonist Pioglitazone Fails to Alter the Abuse Potential of Heroin,
      But Does Reduce Heroin Craving and Anxiety.
AB  - Possibly through its effects on glia, the peroxisome proliferator-activated gamma
      receptor (PPARgamma) agonist pioglitazone (PIO) has been shown to alter the
      effects of heroin in preclinical models. Until now, these results have not been
      assessed in humans. Heroin-dependent participants were randomized to either
      active (45 mg, n = 14) or placebo (0 mg, n = 16) PIO maintenance for the duration
      of the three-week study. After stabilization on buprenorphine (8 mg),
      participants began a two-week testing period. On the first to fourth test days,
      participants could self-administer drug or money by making verbal choices for
      either option. On the fifth day, active heroin and money were administered and
      participants could work to receive heroin or money using a progressive ratio
      choice procedure. Test days 6-10 were identical to test days 1-5 with the
      exception that, during one of the test weeks, placebo was available on the first
      four days, and during the other week heroin was available. PIO failed to alter
      the reinforcing or positive subjective effects of heroin, but it did reduce
      heroin craving and overall anxiety. Although we were unable to replicate the
      robust effects found in preclinical models, these data provide an indication of
      drug effects that deserves further exploration.

PMID- 30204555
TI  - What do people really think about grief counseling? Examining community
      attitudes.
AB  - To understand why bereaved people who are highly distressed significantly
      underutilize grief counseling and therapy, we surveyed adults (N = 156) to
      investigate community attitudes toward grief counseling. Overall attitude was
      positive and women reported a significantly more positive attitude than men;
      there were no associations between attitude and age, country of birth, previous
      counseling, or bereavement experience. After controlling for gender, beliefs and
      affects explained attitudes toward grief counseling; behavioral responses did
      not. Targeting beliefs about grief counseling may promote positive attitudes so
      that people most likely to benefit from intervention will be more likely to seek
      it.

PMID- 30204556
TI  - A Propensity Score Analysis of Clostridium difficile Infection among Adult Trauma
      Patients.
AB  - BACKGROUND: Clostridium difficile infection (CDI) is now the most common cause of
      health-care-associated infection and carries a mortality rate ranging from 5-30%.
      Previously, trauma patients in whom CDI developed were thought to represent a
      unique younger at-risk population. This study aimed to establish the incidence of
      CDI among adult trauma patients. We hypothesized that these patients would have
      increased risk of death, intensive care unit (ICU) length of stay (LOS), and
      hospital LOS compared with trauma patients without CDI. PATIENTS AND METHODS: A
      retrospective study of all adult trauma patients admitted for greater than 48
      hours to a single Level I trauma center between 2014 and 2016 was conducted.
      Analysis was performed using 1-to-5 propensity score matching with the aim to
      analyze the relationship between CDI, death, and other outcome variables.
      RESULTS: Between 2014 and 2016, of 4893 trauma patients admitted for >48 hours,
      27 (0.6%) patients received a diagnosis of CDI. These patients had a mean age of
      55.6 years, mean injury severity score (ISS) of 22.4, and mortality rate of 9.1%.
      Of these patients, 22 were able to find appropriate propensity score matches.
      After adjusting for important covariables, there was no significant difference in
      death between CDI and non-CDI patients (odds ratio = 0.39, 95% confidence
      interval [CI]: 0.06-2.57, adjusted p = 0.66). In addition, there was no
      significant difference in ICU LOS between the two groups (relative mean [RM]:
      1.55, 95% CI: 1.04-2.33, adjusted p = 0.0971). The CDI patients, however, did
      have a significantly longer hospital LOS, compared with non-CDI patients (RM =
      1.39, 95% CI: 1.16-1.66, adjusted p = 0.0017). CONCLUSIONS: Among trauma patients
      admitted >48 hours CDI occurred at a rate of 0.6%, much lower than anticipated.
      Patients in whom CDI developed had a significantly longer hospital LOS however,
      had no significant difference in odds of mortality or ICU LOS compared to
      patients without CDI.

PMID- 30204557
TI  - Mindfulness-Based Stress Reduction and Mindfulness-Based Cognitive Therapy with
      Older Adults: A Qualitative Review of Randomized Controlled Outcome Research.
AB  - OBJECTIVE: Many older adults cope with various chronic physical health
      conditions, and in some cases, with mental health and/or cognitive difficulties.
      Mindfulness-based interventions offer an evidence-based, mind-body complementary
      treatment approach for a wide range of comorbidities, yet most investigations
      were conducted with young or middle-aged adults. The purpose of this review was
      to identify randomized controlled trials (RCTs) of two leading mindfulness-based
      interventions conducted with older adults. METHODS: Our search of five databases
      identified seven RCT investigations of either Mindfulness-Based Stress Reduction
      (MBSR) or Mindfulness-Based Cognitive Therapy (MBCT) conducted exclusively with
      older adults. RESULTS: Results generally supported the use of MBSR for chronic
      low back pain, chronic insomnia, improved sleep quality, enhanced positive
      affect, reduced symptoms of anxiety and depression, and improved memory and
      executive functioning. In a sample of older adults exhibiting elevated anxiety in
      the absence of elevated depression, MBCT effectively reduced symptoms of anxiety.
      CONCLUSIONS: This review highlights the feasibility and possible benefits of MBSR
      and MBCT for older adults. Additional large scale RCTs conducted with older
      adults coping with the range of physical, behavioral, and cognitive challenges
      older adults commonly face still are needed. CLINICAL IMPLICATIONS: MBSR may be a
      promising intervention for older adults experiencing a variety of health concerns
      and possibly even cognitive decline. MBCT may reduce geriatric anxiety, although
      its effects on geriatric depression were not measured.

PMID- 30204558
TI  - Social Interaction Anxiety, Alexithymia, and Drinking Motives in Australian
      University Students.
AB  - In young adults at university, social interaction anxiety has been linked to
      elevated risk of alcohol-related problems, as has alexithymia. The present study
      sought to assess whether social interaction anxiety is, like alexithymia,
      associated with the primary motive of drinking to cope with negative affect.
      There were 126 undergraduates (76 females, 50 males), aged 18-25 years, who were
      recruited from two southeast Queensland universities to complete validated self
      report measures of problematic drinking, alexithymia, drinking motives, and
      social interaction anxiety. As predicted, social interaction anxiety was
      positively related to problematic drinking and coping motives for drinking.
      Alexithymia mediated the relationship of social interaction anxiety with coping
      motives. Findings were consistent with a developmental hypothesis of the links
      between social anxiety, alexithymia, and drinking motives. Given the cross
      sectional design of the current study, longitudinal research is ultimately needed
      to confirm such interpretations of alexithymia and alcohol use among socially
      anxious young adults at university.

PMID- 30204560
TI  - Pharmacotherapy of adjustment disorder: A review.
AB  - BACKGROUND: Adjustment disorder has been reconceptualized as a trauma- and
      stressor-related condition, and there is a growing understanding of the
      psychobiology of stress responses. Against this context it is timely to review of
      the pharmacotherapy of adjustment disorder. METHODS: A comprehensive electronic
      database (Pubmed) was searched for randomised controlled trials of the
      pharmacotherapy of adjustment disorder. Data from each trial were extracted and
      collated. RESULTS: To date there have been relatively few controlled trials in
      this area. Comparator trials provide limited support for a number of
      antidepressant agents, and a series of studies indicate that etifoxine is
      superior to buspirone and benzodiazepines for adjustment disorder with anxiety.
      CONCLUSIONS: The work done has been useful insofar as it provides clinicians with
      some insights into the advantages and disadvantages of a number of
      pharmacotherapy options. Additional rigorously designed trials are needed to
      further advance the field.

PMID- 30204559
TI  - Anxiolytics targeting GABAA receptors: Insights on etifoxine.
AB  - OBJECTIVES: Anxiety and adjustment disorders are among the most prevalent mental
      health conditions. This review focuses on gamma-aminobutyric acid receptor type A
      (GABAAR)-mediated anxiolysis, describing the action of both endogenous and
      exogenous modulators of GABAAR. Future directions and innovative strategies to
      alleviate anxiety symptoms are discussed, with a particular emphasis on
      etifoxine. METHODS: We used available data from the recent literature to update
      the mode of action of anxiolytics. We focussed our search on anxiolytics acting
      at GABAARs, as well as on the pharmacological properties of formerly and
      currently prescribed anxiolytics. RESULTS: Considering the adverse effects of
      current treatments aimed at increasing inhibitory controls, optimisation of
      existing pharmacotherapies is of crucial importance. Among the alternative
      compounds targeting the GABAergic system, translocator protein (TSPO) ligands,
      such as etifoxine (EFX), which promote endogenous neurosteroidogenesis, are
      emerging as promising candidates for anxiety relief. In several papers comparing
      the efficacy of benzodiazepines and EFX, EFX showed interesting properties with
      limited side effects. Indeed, neurosteroids are potent GABAAR modulators with
      highly underrated anxiolytic properties. CONCLUSIONS: Novel therapeutic
      strategies have been emerging following the recognition of neurosteroids as
      potent anxiolytics. Featured at the top of the list for well-tolerated anxiety
      relief, TSPO ligands such as etifoxine appear promising.

PMID- 30204561
TI  - The psychobiology of stress, depression, adjustment disorders and resilience.
AB  - OBJECTIVES: This paper focuses on the psychobiology of stress, depression,
      adjustment disorders (ADs), and resilience. Since the ADs fall under the rubric
      in DSM-5 of Trauma and Stressor-Related Disorders, essentials of the
      psychobiology of stress-response syndromes will be reviewed. METHODS: A narrative
      review of the psychobiology of stress-response syndromes is undertaken, and the
      implications for our understanding of ADs are discussed. RESULTS: Advances in our
      understanding of the psychobiology of stress-response syndromes provide an
      important foundation for understanding ADs, and for conceptualizing their
      diagnosis, as well as issues of resilience. CONCLUSIONS: Future investigations of
      the psychobiology of trauma- and stressor-related disorders may shed additional
      light on ADs, and ultimately improve their treatment.

PMID- 30204562
TI  - Adjustment disorder diagnosis: Improving clinical utility.
AB  - OBJECTIVES: Adjustment disorder (AD) is a frequent diagnosis in clinical practice
      worldwide. After long neglect in mental health research, the new DSM definition
      and in particular the ICD-11 model of AD is about to create a fresh impulse for
      research on AD and for refined clinical use of the diagnosis. METHODS: This paper
      outlines the clinical features of AD according to the ICD-10, ICD-11 and DSM-5
      definitions, and provides case vignettes of patients with AD with clinical
      presentations of dominating anxiety, depressed mood or mixed symptom
      presentations. The available clinical assessments and diagnostic tools are
      described in detail, together with findings on their psychometric properties.
      RESULTS: The current AD definitions are consistent with a new nosological
      grouping of AD with posttraumatic stress disorder in the chapter on trauma- and
      stressor-related disorders, or stress response syndromes. CONCLUSIONS: This
      nosological specification opens new avenues for neurobiological and psychological
      research on AD and for developing novel therapies.

PMID- 30204564
TI  - New perspectives on adjustment disorder.

PMID- 30204563
TI  - Psychotherapy of adjustment disorders: Current state and future directions.
AB  - OBJECTIVES: This narrative review article provides an overview of current
      psychotherapeutic approaches specific for adjustment disorders (ADs) and outlines
      future directions for theoretically-based treatments for this common mental
      disorder within a framework of stepped care. METHODS: Studies on psychological
      interventions for ADs were retrieved by using an electronic database search
      within PubMed and PsycINFO, as well as by scanning the reference lists of
      relevant articles and previous reviews. RESULTS: The evidence base for
      psychotherapies specifically targeting the symptoms of AD is currently rather
      weak, but is evolving given several ongoing trials. Psychological interventions
      range from self-help approaches, relaxation techniques, e-mental-health
      interventions, behavioural activation to talking therapies such as psychodynamic
      and cognitive behavioural therapy. CONCLUSIONS: The innovations in DSM-5 and
      upcoming ICD-11, conceptualising AD as a stress-response syndrome, will hopefully
      stimulate more research in regard to specific psychotherapeutic interventions for
      AD. Low intensive psychological interventions such as e-mental-health
      interventions for ADs may be a promising approach to address the high mental
      health care needs associated with AD and the limited mental health care resources
      in most countries around the world.

PMID- 30204566
TI  - Choosing a Nursing Home.

PMID- 30204565
TI  - Characteristics of Prescription-Opioid-Impaired and Other Substance-Impaired
      Drivers in Rural Appalachian Kentucky.
AB  - Previous studies have highlighted the prescription opioid epidemic in rural
      Appalachia and its associated risk behaviors; however, no studies have examined
      prescription-opioid-impaired driving as a consequence of this epidemic. The
      purpose of the present study was to describe prescription-opioid-impaired drivers
      in rural Appalachian Kentucky and examine how they are similar to and different
      from other substance-impaired drivers from the region. A sample of convicted DUI
      offenders from rural Appalachian Kentucky completed a confidential research
      interview focused on their substance use, mental health, and criminal activity.
      Prescription-opioid-impaired drivers (n = 33) were compared to other drug
      impaired drivers (n = 29) and to alcohol-only-impaired drivers (n = 44). Overall,
      prescription-opioid-impaired drivers had a similar prevalence of illicit
      substance use and criminal activity, including impaired driving frequency, to
      other drug-impaired drivers, but had a higher prevalence of illicit substance use
      and more frequent impaired driving when compared to alcohol-only-impaired
      drivers. Study implications include the importance of comprehensive substance
      abuse assessment and treatment for DUI offenders and the need for tailored
      interventions for prescription-opioid-impaired and other drug-impaired drivers.

PMID- 30204567
TI  - Multifractality of Unperturbed and Asymmetric Locomotion.
AB  - The purpose of this study was to explore the extent of multifractality in
      unperturbed and constrained locomotion, and to determine if multifractality
      predicted gait adaptability. Young, healthy participants (n = 15) walked at
      preferred and slow speeds, as well as asymmetrically (one leg at half speed) on a
      split-belt treadmill. Stride time multifractality was assessed via local
      detrended fluctuation analysis, which evaluates the evolution of fluctuations
      both spatially and temporally. Unperturbed walking exhibited monofractal
      behavior. Asymmetric walking displayed greater multifractality in the faster
      moving limb, indicating more intermittent periods of extreme high or low
      variance. Multifractality was not associated with adaptation to asymmetric
      walking. These findings further suggest that unperturbed locomotion is
      monofractal and establish that perturbed walking yields multifractal behavior.

PMID- 30204568
TI  - Building Recovery Capital: The Role of "Hitting Bottom" in Desistance and
      Recovery from Substance Abuse and Crime.
AB  - The aim of this article is to explore the role of "hitting bottom" as a
      motivation to initiate a recovery process and desistance from crime and substance
      use disorders (SUDs), and in building recovery capital (RC). Researchers and
      practitioners have long been interested in why and how offenders desist from
      crime. Desistance and recovery from crime and SUDs have also been linked to
      negative turning points, such as hitting bottom, which represents
      multidimensional suffering with physiological, familial, social, and criminal
      implications. The deleterious outcomes of SUDs cause individuals to lose their
      social and personal resources and hit bottom. According to the conservation of
      resources model, in the context of actual or potential loss of resources,
      individuals strive to maintain, protect, and build them. Thus, hitting bottom not
      only provides the initial motivation for change, but also drives individuals to
      build personal resources. The prospects for successful recovery are dependent
      upon the individual's personal and social resources, or RC. This article
      represents a first step in examining the role of hitting bottom in building RC in
      the process of long-term recovery. The conclusions may have theoretical as well
      as practical implications.

PMID- 30204570
TI  - Moderators of treatment outcomes in a partial hospitalization and intensive
      outpatient program for eating disorders.
AB  - Eating disorders cause a number of severely impairing symptoms that may require
      more intensive intervention that is available through outpatient therapy
      services. The PHP/IOP level of care may be an effective mode of treatment in
      these cases, but few studies have examined overall outcomes or treatment
      moderators for this level of care. Using a large sample from a PHP/IOP
      specifically designed for the treatment of eating disorders, the current study
      examines a variety of symptoms (eating disorder severity, quality of life,
      depression, etc.) from admission to discharge, as well as potential moderators of
      treatment, including demographic and clinical factors. Overall, the PHP/IOP level
      of care was found to improve treatment outcomes. Age, race, gender, and
      depression were found to moderate the change in quality of life and functional
      impairment. Additionally, patients diagnosed with anorexia nervosa had
      significantly lowered quality of life and greater eating disorder symptomatology
      than all other diagnoses. The results of this study can help to inform clinical
      practice and help guide in treatment decisions at the partial hospitalization
      level of care.

PMID- 30204569
TI  - Antimicrobial Resistance in Commensal Escherichia coli Isolated from Pigs and
      Pork Derived from Farms Either Routinely Using or Not Using In-Feed
      Antimicrobials.
AB  - The aims of this study were (i) to evaluate whether routine in-feed antimicrobial
      use in pigs or not resulted in differences in antimicrobial resistance (AMR) E.
      coli at different pig producing stages, and (ii) to determine whether resistant
      strains were presented in pig meat postslaughter. A total of 300 commensal E.
      coli isolates were obtained and examined for antibiograms, AMR genes, plasmid
      replicons, and molecular types. The isolates were from two farms either using (A)
      or not using in-feed antimicrobials (NA), sampled four times during the
      production cycle and once postslaughter. E. coli resistant to aminoglycosides
      containing aadA1, aadA2, and aadB and extended-spectrum beta-lactamase-producing
      (ESBLP) E. coli containing blaCTX-M-1 were significantly increased in the nursery
      and growing periods in farm A compared to farm NA. IncI1-Igamma and IncHI2 were
      common in the nursery period and were shown to transfer blaCTX-M genes by
      conjugation. ST10 was the most common type only found in live pigs. ST604, ST877,
      ST1209, and ST2798 ESBLP were found only in live pigs, whereas ST72, ST302, and
      ST402 ESBLP were found in pig meat.

PMID- 30204571
TI  - Treatment of chronic infected post-oncological wounds with a dermal matrix: two
      case studies.
AB  - The reconstruction of complex wounds in patients with comorbidities in the lower
      extremities is a challenging problem for surgeons. Skin grafting is frequently
      used to cover large skin defects, but it has several limits, including unwanted
      outcomes resulting from scars, poor elasticity and limitations in joint movement
      due to contractures. Locoregional flaps, particularly in the lower limbs, have
      limited application due to the size of the defect. Tissue engineering of the skin
      has offered major improvements in the coverage of large defects. Dermal matrix
      can be applied in order to generate a new dermis that allows good re
      epithelialisation or skin grafting at a later stage. The reconstruction of large
      lower limb defects is more complicated in the case of chronic wounds showing no
      tendency to heal due to chronic infection. For all surgeons, it is very important
      to prevent the formation of a biofilm or manage it when it is already established
      before undertaking surgical procedures that involve a dermal matrix. We report
      our reconstruction strategy of chronic infected neoplastic ulcers of the lower
      extremities with a dermal matrix and our postoperative dressing protocol.

PMID- 30204572
TI  - How many patients do I need? (Part 1).

PMID- 30204573
TI  - Read, listen, question and debate.

PMID- 30204574
TI  - Role of platelet-rich plasma in healing diabetic foot ulcers: a prospective
      study.
AB  - OBJECTIVE: To evaluate the role of platelet-rich plasma (PRP) in healing diabetic
      fool ulcers (DFUs), and to compare the rate of healing and final outcome with
      conventional therapy. METHOD: A prospective study conducted between October 2013
      and July 2015. Participants were divided in to two groups: a study group in which
      PRP was used and a control group receiving standard therapy. Wound assessment was
      carried out according to the Bates-Jensen Wound Assessment Tool at 0, 7, 14, 21
      and 28 days. RESULTS: A total of 55 patients were recruited to the study. There
      were 29 patients in the study group and 26 patients in the control group. After
      application of PRP, there was significant improvement in mean wound score and
      significant percent improvement in wound score in the study group (p<0.0001).
      Complete healing occurred in all patients in the study group in (mean score and
      standard deviation) 36.7+/-3 days compared with 60.6+/-3.7 days in the control
      group (p<0.0001). There were no unwanted side effects in patients using the PRP
      in this study. CONCLUSION: PRP appears to be a promising agent in the management
      of DFUs. In this study, DFUs healed more quickly in the study group than in the
      control group. There was also significant percent improvement in wound score as
      compared with debridement and dressing only. If proper selection criteria are
      applied, PRP could be a useful aid to wound healing in people with DFUs.

PMID- 30204576
TI  - Shockwave therapy in selected soft tissue diseases: a literature review.
AB  - OBJECTIVE: The aim of our study is to present the current state of knowledge on
      the use of shockwave therapy (SWT) in the treatment of soft tissue wounds, by
      reviewing the available literature. METHOD: Medical databases were searched for
      articles using the keywords: 'shockwave AND wound healing', 'shockwave AND
      ulcers', 'shockwave AND burns', 'shockwave AND bedsores', 'shockwave AND diabetic
      foot ulcer', 'ESWT AND wound healing', 'shock wave AND diabetic gangrene'.
      RESULTS: A total of 14 scientific articles were included in the study which
      described the methodology of treatments and list the type of generator, physical
      parameters used during the procedure, number of treatments and the type of
      treated wounds. From these articles, 191 soft tissue wounds were analysed.
      CONCLUSION: Evidence from the articles analysed in this study suggests a
      beneficial effect of SWT to treat diabetic foot ulcers, venous leg ulcers,
      pressure ulcers and burns. SWT can be used in combination with standard treatment
      in soft tissue wounds.

PMID- 30204575
TI  - Cell salvage in acute and chronic wounds: a potential treatment strategy.
      Experimental data and early clinical results.
AB  - On 9 May 2018, the authors took part in a closed panel discussion on the impact
      of cell salvage in acute and chronic wounds. The goal was to deliberate the
      possible use of plurogel micelle matrix (PMM) as a new treatment strategy for
      wound healing and the authors openly shared their experiences, thoughts,
      experimental data and early clinical results. The outcome of the panel discussion
      has been abridged in this paper. The cell membrane consists of a lipid bilayer,
      which provides a diffusion barrier separating the inside of a cell from its
      environment. Cell membrane injury can result in acute cellular necrosis when
      defects are too large and cannot be resealed. There is a potential hazard to the
      body when these dying cells release endogenous alarm signals referred to as
      'damage (or danger) associated molecular patterns' (DAMPs), which trigger the
      innate immune system and modulate inflammation. Cell salvage by membrane
      resealing is a promising target to ensure the survival of the individual cell and
      prevention of further tissue degeneration by inflammatory processes. Non-ionic
      surfactants such as poloxamers, poloxamines and PMM have the potential to
      resuscitate cells by inserting themselves into damaged membranes and stabilising
      the unstable portions of the lipid bilayers. The amphiphilic properties of these
      molecules are amenable to insertion into cell wall defects and so can play a
      crucial, reparative role. This new approach to cell rescue or salvage has gained
      increasing interest as several clinical conditions have been linked to cell
      membrane injury via oxidative stress-mediated lipid peroxidation or thermal
      disruption. The repair of the cell membrane is an important step in salvaging
      cells from necrosis to prevent further tissue degeneration by inflammatory
      processes. This is applicable to acute burns and chronic wounds such as diabetic
      foot ulcers (DFUs), chronic venous leg ulcers (VLUs), and pressure ulcers (PUs).
      Experimental data shows that PMM is biocompatible and able to insert itself into
      damaged membranes, salvaging their barrier function and aiding cell survival.
      Moreover, the six case studies presented in this paper reveal the potential of
      this treatment strategy.

PMID- 30204577
TI  - Clinical and in vitro performance of an antibiofilm Hydrofiber wound dressing.
AB  - OBJECTIVE: To compare the clinical and in vitro performance of a next-generation
      antibiofilm silver dressing (NGAD) with an established antimicrobial dressing
      technology that was developed before the recognition of wound biofilm as a
      clinical challenge. METHOD: Real-life evaluations of challenging wounds managed
      previously with cadexomer iodine (CI) dressings followed by switching to NGAD
      were evaluated alongside electron, confocal and light microscopy images from a
      challenging, in vitro, exuding chronic wound model. Clinical case studies on the
      use of CI and NGAD dressings are presented to further explore the real-life
      evidence and in vitro findings. RESULTS: We assessed 13 non-healing wounds that
      had been managed with protocols including CI dressings. After a median of four
      weeks, switching to the NGAD as primary dressing resulted in improvements in nine
      wounds and healing in two wounds, with associated improvements in wound bed
      appearance, while dressing usage was the same as or lower than before. The NGAD
      was observed to prevent the development of Staphylococcus aureus- Pseudomonas
      aeruginosa biofilm over three days, in contrast to the CI dressing, which
      appeared to support biofilm development once the active antimicrobial was
      exhausted from its carrier material. Clinical case studies exhibited this
      exhaustion as 'whiting out' of the dressing, with wound biofilm observed from
      samples taken following dressing use. Positive wound and patient outcomes were
      observed in two cases following the switch from a CI primary dressing to the
      NGAD, in highly exuding and infected wounds. CONCLUSION: Antimicrobial dressings
      may be effective against biofilm in some laboratory models, but their
      effectiveness as a wound dressings in protocols of care must be verified
      clinically.

PMID- 30204578
TI  - Clinical assessment of a foam dressing containing growth factor-enhancing
      hydrated polyurethanes.
AB  - OBJECTIVE: This study assesses a novel dressing concept in venous leg ulcer (VLU)
      patients. It is based on boosting endogenous growth factor activities synthesised
      by functional granulation tissue. METHODS: Patients received treatment for eight
      weeks with a hydrated polyurethane-containing foam dressing plus concomitant
      compression therapy. Wound area reduction (WAR), percentage of wounds achieving a
      relative WAR of >=40% and >=60%, wound pain ratings for the last 24 hours and at
      dressing changes, EQ-5D Quality of Life questionnaire data, dressing handling and
      safety parameters were recorded. RESULTS: There were 128 patients who received
      treatment and data for 123 wound treatment courses were documented. Wound area
      size decreased from 13.3+/-9.8cm2 to 10.5+/-12.2cm2 at week eight and median
      relative WAR was 48.8%. At week eight, a relative WAR >=40% was reached by 54.5%
      of the wounds, 41.5% reached a relative WAR of >=60% and complete healing was
      observed in 13.5% of wounds. Median wound pain ratings (last 24 hours before
      dressing change) declined significantly from 30 to 15.5 (100 visual analogue
      scale [VAS], p=0.0001) and pain at dressing changes from 30 to 12.5 (p<=0.0001).
      The EQ-5D VAS rating increased from 58.4+/-19.2mm to 63.1+/-19.1mm (p=0.0059).
      CONCLUSION: This clinical assessment shows that the concept of boosting
      endogenous growth factors through hydrated polyurethanes has the potential to
      accelerate WAR in VLU patients while decreasing pain levels and improving quality
      of life parameters.

PMID- 30204579
TI  - A clinical observation evaluation of bioactive soluble beta-glucan gel compared
      with standard care.
AB  - OBJECTIVE: Clinicians across all health-care settings are challenged daily by
      wounds that are slow or static in healing due to time constraints, reduced
      resources and the negative impact upon the patient's quality of life (QoL).
      Community settings are particularly challenging due to the varied environments,
      patient social, psychological and financial constraints, and multi-clinician
      wound care monitoring. The aim of this clinical evaluation is to clinically
      evaluate bioactive soluble beta-glucan gel (BSBG) on those wounds that have
      stalled at four weeks as an adjunct to normal standards of care. METHOD: A
      clinical observational evaluation was undertaken within a large community
      setting, reviewing patients who self-presented with stalled healing/chronic
      wounds, and the effects upon adding a BSBG gel twice a week for eight weeks as
      part of their set standard care. Formulary cleansing and dressing products were
      continued and results monitored by a designated clinician. All data was collected
      as part of the patient's normal wound review routine in relation to primary
      outcome of wound reduction with secondary outcomes relating to pain reduction,
      slough and necrosis reduction, exudate reduction and adverse events. RESULTS: At
      six months, analysis of data demonstrated >2-times a higher rate of healing in
      chronic wounds with eight weeks' initial treatment and >4-times a higher rate of
      healing over six months in those patients with ulceration (PU, VLU, DFU). A
      reduction of per patient care cost saving was achieved across the treatment group
      compared with the standard care retrospective group. CONCLUSION: The
      administration of a wound healing gel within a moderate size cohort of patients
      presenting with chronic wounds resulted in improved wound reduction and
      significant cost savings.

PMID- 30204580
TI  - Treatment options for partial auricle reconstruction: a prospective study of
      outcomes and patient satisfaction.
AB  - OBJECTIVE: To evaluate the various methods and outcomes of post-traumatic partial
      auricle wound reconstruction, and to review the benefit to the patient's quality
      of life and their psychological improvement after the operation. METHODS: The
      prospective study included patients who suffered from post-traumatic partial
      auricular wounds. The defects were repaired using various techniques including
      simple local cutaneous advancement flaps, tube flaps, cartilage framework using
      conchal and costal cartilage with local skin flap cover. RESULTS: A total of 18
      patients were included, with a male predominance (sex ratio: 7:2), mean age with
      standard deviation of 31.66 +/-9.27 years. Causes included road traffic accident
      (RTA), assault, human and insect bite and avulsion injuries. Injuries were
      sustained in the upper third of the auricle (n=8); middle third (n=5), lower
      third (n=3), and upper two-thirds (n=2). Out of the 18 patients, wound were
      repaired using post auricular mastoid skin flap (n=7); local superior and
      inferior chondrocutaneous flap (n=3); costal cartilage as a cartilage framework
      (n=4), temporoparietal fascia used to cover the costal cartilage graft (n=1), and
      conchal cartilage as a cartilage framework (n=3). In our study 13/18 patients
      were 'highly satisfied' with the aesthetic outcome, 3/18 were 'moderately
      satisfied', and 2/18 were 'slightly satisfied'. None were dissatisfied by the
      postoperative result. In terms of objective assessment, patient outcome in two
      patients was graded 'good' while the outcome of remaining patients (n=16) was
      graded as 'excellent'. CONCLUSIONS: The use of skin flaps in the post-auricular
      region and the mastoid region associated with or without cartilage framework
      yields good cosmetic and functional result. The various techniques used for ear
      reconstruction yielded 100% satisfactory results in terms of functional outcome
      as well as boosting the confidence of patients.

PMID- 30204581
TI  - Occupational exposures to agricultural dust by Western Australian wheat-belt
      farmers during seeding operations.
AB  - Agricultural operations routinely expose farm workers to high levels of soil dust
      and other airborne particulate matter that have been linked to adverse health
      outcomes. The main objective of this study was to investigate exposure to
      agricultural dust during seeding operations of Western Australian farm workers.
      Twenty-one wheat-belt farms were recruited to participate in the study. Data were
      collected over the six-week seeding period of April - June 2014. Each farm was
      visited once, and workers were asked to complete a workplace survey that asked
      questions related to minimizing exposure to agricultural dusts and occupational
      health and safety issues on their farm. Farmers were also asked to simultaneously
      participate in monitoring of personal exposure to inhalable or respirable dust
      along with real-time monitoring for particulate air pollution in their tractor
      cabin. Sampling was undertaken for 4-hrs. The results showed that, on average,
      Western Australian farmers were exposed to personal respirable dust
      concentrations above the Australian Institute of Occupational Hygienists
      recommended guideline values, with some farmers being exposed to concentrations
      up to seven times higher than the value for respirable dusts. In comparison, in
      cabin dust concentrations were lower, although some individual tractors recorded
      intermittently higher levels, which might be attributed to the type of work
      activity or process being undertaken. Remaining in tractor cabins with closed
      doors and windows with properly maintained seals might minimize the infiltration
      of hazardous dusts and may provide some protection from dust exposures. Future
      research should focus on educating and providing farm owners and workers with
      more information on adopting work processes and procedures related to minimising
      harmful exposures to agricultural dusts.

PMID- 30204582
TI  - Abyssibacter profundi gen. nov., sp. nov., a marine bacterium isolated from
      seawater of the Mariana Trench.
AB  - A Gram-stain-negative, strictly aerobic, short-rod-shaped bacterium, motile by a
      single polar flagellum, designated OUC007T, was isolated from seawater at a depth
      of 1000 m in the Mariana Trench. Phylogenetic analysis based on 16S rRNA gene
      sequences indicated that strain OUC007T formed a lineage within the family
      Salinisphaeraceae that was distinct from the most closely related genera
      Oceanococcus and Salinisphaera, with 16S rRNA gene sequences similarities ranging
      from 89.3 to 90.8 %, respectively. Strain OUC007T grew with 0-7 % (w/v) NaCl
      (optimum, 2-3 %), at 10-45  degrees C (37  degrees C) and at pH 7.0-9.0 (7.0
      8.0). The major respiratory quinone was ubiquinone-8 (Q-8). The polar lipids of
      strain OUC007T comprised one phosphatidylethanolamine and three unidentified
      polar lipids. The predominant fatty acid (more than 10 % of total fatty acids)
      was summed feature 8 (C18 : 1omega7c or/and C18 : 1omega6c). The DNA G+C content
      of strain OUC007T was 63.1 mol%. On the basis of polyphasic taxonomic analysis,
      the strain OUC007T is considered to represent a novel species in a new genus of
      the family Salinisphaeraceae, for which the name Abyssibacter profundi gen. nov.,
      sp. nov. is proposed. The type strain is OUC007T (=KCTC 52933T=MCCC 1K03450T).

PMID- 30204583
TI  - Staphylococcus cornubiensis sp. nov., a member of the Staphylococcus intermedius
      Group (SIG).
AB  - We here describe a novel species in the Staphylococcus intermedius Group (SIG)
      which is phenotypically similar to Staphylococcus pseudintermedius but is
      genomically distinct from it and other SIG members, with an average nucleotide
      identity of 90.2 % with its closest relative S. intermedius. The description of
      Staphylococcus cornubiensis sp. nov. is based on strain NW1T (=NCTC 13950T=DSM
      105366T) isolated from a human skin infection in Cornwall, UK. Although
      pathogenic, NW1T carries no known virulence genes or mobilizable antibiotic
      resistance genes and further studies are required to assess the prevalence of
      this species in humans as well as its potential presence in companion animals.

PMID- 30204585
TI  - Sphingomonas floccifaciens sp. nov., isolated from subterranean sediment.
AB  - A Gram-stain-negative, non-motile, non-sporulating, rod-shaped, orange-pigmented
      bacterium, designated strain FQM01T, was isolated from a subterranean sediment
      sample in the Mohe permafrost area, China. Strain FQM01T grew optimally at 25 
      degrees C, pH 7.0 and NaCl concentration of 0 % (w/v). Phylogenetic analysis
      based on 16S rRNA gene sequences showed that strain FQM01T belonged to the genus
      Sphingomonas. The closest phylogenetic relative was Sphingomonas
      spermidinifaciens GDMCC 1.657T (97.6 %), followed by Sphingomonas mucosissima DSM
      17494T (97.2 %). The DNA G+C content of the isolate was 66.9 mol%. Strain FQM01T
      contained Q-10 as the predominant ubiquinone, and C18 : 1omega6c and/or C18 :
      1omega7c, C16 : 1omega6c and/or C16 : 1omega7c, C16 : 0, C14 : 0 2-OH and C18 :
      1omega7c 11 methyl as the major fatty acids. Major polar lipids were
      phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine,
      phosphatidylcholine, sphingoglycolipid and an unidentified glycolipid. Only sym
      homospermidine was detected as the polyamine. On the basis of phylogenetic and
      phenotypic data, strain FQM01T is considered to represent a novel species of
      Sphingomonas for which the name Sphingomonasfloccifaciens sp. nov. is proposed.
      The type strain is FQM01T (=CGMCC 1.15797T=KCTC 52630T).

PMID- 30204584
TI  - Psychromicrobium lacuslunae sp. nov., isolated from a high altitude lake.
AB  - The novel strain IHBB 11108T was a psychrotolerant and alkaliphilic bacterium
      isolated from the subsurface water of Chandra Tal Lake in the Lahaul-Spiti valley
      located in the Indian trans-Himalayas. Cells were Gram-stain-positive, aerobic,
      non-motile, catalase-positive and oxidase-negative. The strain grew at 5-37 
      degrees C (optimum 28  degrees C), pH 5.0-12.0 (optimum pH 7.0) and with up to 8
      % NaCl (optimum 1 %). The 16S rRNA gene sequence analysis revealed the highest
      relatedness of strain IHBB 11108T with Psychromicrobium silvestre DSM 102047T
      (97.5 %), Arthrobacter russicus DSM 14555T (97.4 %) and Renibacterium
      salmoninarum ATCC 33209T (97.4 %). The strain contained a quinone system with
      57.2 % MK-9(H2), 39.1 % MK-10(H2), 3.0 % MK-8(H2) and 0.7 % MK-7(H2). The polar
      lipids detected were diphosphatidylglycerol, dimannosylglyceride,
      phosphatidylinositol, phosphatidylglycerol, monogalactosyldiacylglycerol, one
      unidentified glycolipid and four unidentified lipids. The cell-wall peptidoglycan
      structure type was A3alpha l-Lys-l-Thr-l-Ala with substitution of the alpha
      carboxyl group of d-Glu by alanine amide. Anteiso-C15 : 0, iso-C16 : 0 and
      anteiso-C17 : 0 were the predominant fatty acids. The genomic DNA G+C content was
      59.0 mol%. The DNA-DNA relatedness of strain IHBB 11108T was 46.7+/-2.2, 43.1+/
      2.5 and 19.1+/-2.4 % with P. silvestre DSM 102047T, A. russicus DSM 14555T and R.
      salmoninarum ATCC 33209T, respectively. On the basis of the results of the
      phenotypic, chemotaxonomic and phylogenetic analyses, IHBB 11108T is considered
      to represent a novel species of the genus Psychromicrobium for which the name
      Psychromicrobium lacuslunae sp. nov. is proposed. The type strain is IHBB 11108T
      (=MTCC 12460T=MCC 2780T=JCM 31143T=KACC 19070T).

PMID- 30204586
TI  - Mycobacterium decipiens sp. nov., a new species closely related to the
      Mycobacterium tuberculosis complex.
AB  - Two mycobacterial strains with close similarity to the Mycobacterium tuberculosis
      complex (MTBC) were isolated from cutaneous lesions of patients in the USA and
      Italy. At the phenotypic level, similarities to the MTBC included slow growth
      rate, rough morphotype of the unpigmented colonies and nearly identical high
      performance liquid chromatography profiles of mycolic acids. In contrast to the
      MTBC, the strains were niacin- and nitrate-negative, and catalase-positive both
      at 68  degrees C and in semi-quantitative tests. The clinical isolates were more
      closely related to M. tuberculosis than to any other known mycobacterium and
      scored positive with commercial DNA probes (Hologic AccuProbe M. tuberculosis).
      Both average nucleotide identity and genome-to-genome distance suggested the
      strains are different from the MTBC. Therefore, given the distinguishing
      phenotypic and genomic-scale differences, we submit that the strains belong to a
      new species we have named Mycobacteriumdecipiens with type strain TBL 1200985T
      (=ATCC TSD-117T=DSM 105360T).

PMID- 30204587
TI  - Anti-ganglioside antibodies: experience from the Italian Association of
      Neuroimmunology external quality assessment scheme.
AB  - Background Anti-ganglioside antibodies are currently used in the differential
      diagnosis of suspected immune-mediated neuropathies. In-house and increasingly
      used commercial assays seem to perform suboptimally, and comparative information
      on their analytical performance are essentially lacking. Born within the frame of
      guidelines and standardization activities by the Italian Association of
      Neuroimmunology, this external quality assessment scheme (EQAS) is a real-life
      snapshot of the laboratory diagnostics in this field. Methods The EQAS consisted
      of five surplus, anonymized serum samples from patients with clinically-defined
      neuropathies and two serum samples from healthy blood donors. Eight laboratories
      used commercial line-/dot-blots, seven in-house/commercial ELISAs (in addition,
      13 laboratories tested a recently released ELISA by Buhlmann). Only high anti
      ganglioside antibody reactivities were considered, in accordance with
      consolidated recommendations. Results Large variations in anti-ganglioside
      antibody profiles were observed, even, although to a lesser extent, within
      homogeneous classes of assays. Concordance between the profiles and clinical
      phenotypes was also partial. Conclusions Although conducted on a relatively
      small, but representative number of Italian laboratories, this EQAS shows a
      critical between-laboratory disagreement in the test results of anti-ganglioside
      antibodies. Also considering the trend for using certified assays in generalist
      laboratories, strong efforts toward standardization and the identification of the
      best method(s) for their determinations are compellingly needed.

PMID- 30204588
TI  - Impact of continuous renal replacement therapy (CRRT) and other extracorporeal
      support techniques on procalcitonin guided antibiotic therapy in critically ill
      patients with septic shock.

PMID- 30204589
TI  - Euthyroid Graves' disease with spurious hyperthyroidism: a diagnostic challenge.

PMID- 30204590
TI  - Beta-propeller protein-associated neurodegeneration (BPAN) as a genetically
      simple model of multifaceted neuropathology resulting from defects in autophagy.
AB  - Autophagy is an essential and conserved cellular homeostatic process. Defects in
      the core and accessory components of the autophagic machinery would most severely
      impact terminally differentiated cells, such as neurons. The
      neurodevelopmental/neurodegenerative disorder beta-propeller protein-associated
      neurodegeneration (BPAN) resulted from heterozygous or hemizygous germline
      mutations/pathogenic variant of the X chromosome gene WDR45, encoding WD40 repeat
      protein interacting with phosphoinositides 4 (WIPI4). This most recently
      identified subtype of the spectrum of neurodegeneration with brain iron
      accumulation diseases is characterized by a biphasic mode of disease
      manifestation and progression. The first phase involves early-onset of epileptic
      seizures, global developmental delay, intellectual disability and autistic
      syndrome. Subsequently, Parkinsonism and dystonia, as well as dementia, emerge in
      a subacute manner in adolescence or early adulthood. BPAN disease phenotypes are
      thus complex and linked to a wide range of other neuropathological disorders.
      WIPI4/WDR45 has an essential role in autophagy, acting as a phosphatidylinositol
      3-phosphate binding effector that participates in autophagosome biogenesis and
      size control. Here, we discuss recent updates on WIPI4's mechanistic role in
      autophagy and link the neuropathological manifestations of BPAN's biphasic
      infantile onset (epilepsy, autism) and adolescent onset (dystonic, Parkinsonism,
      dementia) phenotypes to neurological consequences of autophagy impairment that
      are now known or emerging in many other neurodevelopmental and neurodegenerative
      disorders. As monogenic WDR45 mutations in BPAN result in a large spectrum of
      disease phenotypes that stem from autophagic dysfunctions, it could potentially
      serve as a simple and unique genetic model to investigate disease pathology and
      therapeutics for a wider range of neuropathological conditions with autophagy
      defects.

PMID- 30204592
TI  - Validation of chronic mild stress in the Wistar-Kyoto rat as an animal model of
      treatment-resistant depression.
AB  - A recent review proposed four criteria for an animal model of treatment-resistant
      depression (TRD): a phenotypic resemblance to a risk factor for depression;
      enhanced response to stress; nonresponse to antidepressant drugs and response to
      treatments effective in TRD, such as deep brain stimulation (DBS) of the
      prefrontal cortex or ketamine. Chronic mild stress (CMS) provides a valid model
      of depression; the Wistar-Kyoto (WKY) rat is considered to be nonresponsive to
      antidepressant drugs. Here, we applied CMS to WKY rats. WKY and Wistar rats were
      exposed to CMS, then treated with saline, imipramine, citalopram or venlafaxine.
      After 5 weeks of CMS and 3 weeks of drug treatment, all WKY groups were implanted
      unilaterally with DBS electrodes in the prefrontal cortex, and examined in
      sucrose intake, elevated plus maze (EPM; decreased entries and time in the open
      arms) and novel object recognition (decreased exploration) tests, following 2*2 h
      of DBS. CMS decreased sucrose intake, open arm entries on the EPM, and object
      recognition. Relative to Wistars, WKY rats showed evidence of increased
      emotionality in the EPM and novel object recognition tests, and a greater impact
      of CMS on body weight gain and open arm entries. Wistars responded to drug
      treatment with an increase in sucrose intake but WKY were nonresponsive to drug
      treatment on all three behavioural tests. With one exception, DBS reversed the
      anhedonic, anxiogenic and dyscognitive effects of CMS in all groups of WKY rats.
      In a further experiment, subacute ketamine (10 mg/kg) also normalized behaviour
      on all three tests. We conclude that WKY rats subjected to CMS meet all four
      criteria for a valid model of TRD, and provide a basis for studying the mechanism
      of action of DBS.

PMID- 30204591
TI  - Neutrophil extracellular trap production contributes to pathogenesis in SIV
      infected nonhuman primates.
AB  - Neutrophil extracellular traps (NETs) are involved in the pathogenesis of many
      infectious diseases, yet their dynamics and impact on HIV/SIV infection have not
      yet been assessed. We hypothesized that SIV infection and the related microbial
      translocation trigger NET activation and release (NETosis), and we investigated
      the interactions between NETs and immune cell populations and platelets. We
      compared and contrasted the levels of NETs between SIV-uninfected, SIV-infected,
      and SIV-infected antiretroviral-treated nonhuman primates. We also cocultured
      neutrophils from these animals with either peripheral blood mononuclear cells or
      platelets. Increased NET production was observed throughout SIV infection. In
      chronically infected animals, NETs were found in the gut, lung, and liver, and in
      the blood vessels of kidney and heart. Antiretroviral therapy (ART) decreased
      NETosis, albeit above preinfection levels. NETs captured CD4+ and CD8+ T cells, B
      cells, and monocytes, irrespective of their infection status, potentially
      contributing to the indiscriminate generalized immune cell loss characteristic to
      HIV/SIV infection, and limiting the CD4+ T cell recovery under ART. By capturing
      and facilitating aggregation of platelets, and through expression of increased
      tissue factor levels, NETs may also enhance HIV/SIV-related coagulopathy and
      promote cardiovascular comorbidities.

PMID- 30204593
TI  - Ultrasound Elastography for Rapid, Real-time Detection of Localized Muscular
      Reaction in Malignant Hyperthermia-susceptible Pigs.
AB  - WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW:
      BACKGROUND:: Halothane and caffeine induce excessive sarcoplasmic calcium
      liberation and skeletal muscle contracture in patients susceptible to malignant
      hyperthermia (MH) and are utilized for diagnosis in the in vitro contracture
      test. Intramuscular injection previously caused a marked local lactate increase
      in MH-susceptible but not in MH-nonsusceptible individuals in vivo. Using shear
      wave elastography, this study evaluated localized changes in muscle stiffness
      after intramuscular injection of halothane and caffeine. METHODS: Microdialysis
      probes were placed into the gracilis muscle of 16 pigs (9 MH-susceptible and 7 MH
      nonsusceptible). After local injection of either halothane or caffeine in
      different concentrations, changes of tissue elasticity surrounding the probe were
      examined by quantitative shear-wave elastography. Local lactate concentrations
      were analyzed spectrophotometrically. RESULTS: Ultrasound elastography detected a
      temporary increase in local muscle rigidity in MH-susceptible but not in MH
      nonsusceptible pigs after 2.5 and 5 vol% halothane and after 10, 40, and 80 mM
      caffeine, whereas there were no differences in the control groups (median
      [interquartile range] for maximum effect after 5 vol% halothane: MH-susceptible:
      97 [31 to 148] vs. MH-nonsusceptible: 5 [-6 to 18] kPa; P = 0.0006; maximum
      effect after 80 mM caffeine: 112 [64 to 174] vs. -3 [-6 to 35] kPa; P = 0.0002).
      These effects were seen rapidly within 5 min. Local lactate concentrations were
      higher in MH-susceptible versus nonsusceptible pigs after 1 and 2.5 vol%
      halothane and 10, 40, and 80 mM caffeine (2.5 vol% halothane: MH-susceptible: 2.8
      [1.9 to 4.4] vs. MH-nonsusceptible: 0.6 [0.6 to 0.7] mmol/l; P < 0.0001; 80 mM
      caffeine: 5.2 [4.1 to 6.3] vs. 1.6 [1.2 to 2.4] mmol/l; P < 0.0001). After 10
      vol% halothane, rigidity and lactate levels were increased in both MH-susceptible
      and MH-nonsusceptible animals. CONCLUSIONS: This pilot study revealed shear-wave
      elastography as a suitable technique for real-time detection of altered tissue
      elasticity in response to pharmacologic stimulation. By considering the
      variability of these results, further test protocol optimization is required
      before elastography could serve as a minimally invasive MH diagnostic test.

PMID- 30204594
TI  - Perioperative Hyperglycemia Management: An Update: Erratum.

PMID- 30204595
TI  - Workflow Eats Optimum Care for Lunch.

PMID- 30204596
TI  - Preclinical testing of 5-amino-1-((1R,2S,3S,4R)-2,3-dihydroxy-4
      methylcyclopentyl)-1H-imidazole-4-carboxamide: a potent protein kinase C-iota
      inhibitor as a potential prostate carcinoma therapeutic.
AB  - Protein kinase C-iota (PKC-iota) is an oncogene overexpressed in many cancer
      cells including prostate, breast, ovarian, melanoma, and glioma. Previous in
      vitro studies have shown that 5-amino-1-((1R,2S,3S,4R)-2,3-dihydroxy-4
      methylcyclopentyl)-1H-imidazole-4-carboxamide (ICA-1s), a PKC-iota specific
      inhibitor, is effective against some cancer cell lines by decreasing cell growth
      and inducing apoptosis. To assess ICA-1s as a possible therapeutic, in-vivo
      studies using a murine model were performed. ICA-1s was tested for stability in
      blood serum and results demonstrated that ICA-1s was stable in human plasma at 25
      and 37 degrees C over a course of 2 h. Toxicity of ICA-1s was tested for both
      acute and subacute exposure. The acute exposure showed patient surviving after 48
      h of doses ranging from 5 to 5000 mg/kg. Subacute tests exposed the patients to
      14 days of treatment and were followed by serum and tissue collection. Aspartate
      aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase, troponin,
      and C-reactive protein serum levels were measured to assess organ function. ICA
      1s in plasma serum was measured over the course of 24 h for both oral and
      intravenous treatments. Heart, liver, kidney, and brain tissues were analyzed for
      accumulation of ICA-1s. Finally, athymic nude mice were xenografted with DU-145
      prostate cancer cells. After tumors reached ~0.2 cm, they were either treated
      with ICA-1s or left as control and measured for 30 days or until the tumor
      reached 2 cm. Results showed tumors in treated mice grew at almost half the rate
      as untreated tumors, showing a significant reduction in growth. In conclusion,
      ICA-1s is stable, shows low toxicity, and is a potential therapeutic for prostate
      carcinoma tumors.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- 30204597
TI  - Quality of Life in Patients With Non-Small Cell Lung Cancer: Structural Equation
      Modeling.
AB  - BACKGROUND: Quality of life (QOL) is important for cancer patients, even for
      survival. However, factors affecting QOL of non-small cell lung cancer (NSCLC)
      patients have not been studied sufficiently. OBJECTIVE: The aims of this study
      were to understand the relationships among social support, resilience, distress,
      and symptom and to identify predictors of QOL for NSCLC patients. METHODS:
      Participants were 212 adult patients who visited an outpatient department at a
      tertiary hospital located in Seoul, Korea. Data were collected using self
      reported questionnaires and clinical records. RESULTS: Social support,
      resilience, distress, symptom burden, and QOL explained 99.9% of the variance in
      QOL. Social support was not a significant predictor of distress and QOL, but a
      significant predictor of resilience. Resilience was a significant predictor of
      both distress and QOL. Distress was not a significant predictor of QOL, but a
      significant predictor of symptom burden. Symptom burden was a significant
      predictor of QOL and had the largest direct effect on QOL. Resilience also had an
      important impact on QOL because resilience influenced QOL in various paths.
      CONCLUSION: This study suggests that social support, resilience, distress, and
      symptom burden are predictors of QOL in an NSCLC population. These predictors had
      direct and indirect effects on each other and on QOL. IMPLICATIONS FOR PRACTICE:
      Developing an interventional program to increase resilience and social support as
      well as to decrease symptom burden and distress may be necessary to improve QOL
      of NSCLC patients.

PMID- 30204598
TI  - A Case of Musical Hallucinations Related to Mirtazapine.
AB  - Musical hallucinations (MHs) are relatively uncommon phenomena sometimes
      encountered in older patients, especially older women. They usually involve
      popular, overlearned music, either entire songs or repetitive snippets. While MHs
      are most commonly associated with hearing loss, they may occur in a variety of
      psychiatric, neurologic, and iatrogenic conditions. We report a 91-year-old man
      whose MHs were causally related to the antidepressant mirtazapine. Although
      mirtazapine is generally well tolerated, it may rarely cause MHs or other
      psychotic symptoms.

PMID- 30204599
TI  - Tandospirone-Induced Rhabdomyolysis.
AB  - BACKGROUND: Rhabdomyolysis involves the release of intracellular contents
      secondary to muscle cell injury; it generally presents with muscle pain and
      weakness. Although several psychotropic agents have been documented as causes of
      rhabdomyolysis, there are no reports of tandospirone-induced rhabdomyolysis.
      CASE: We present the case of a 15-year-old Japanese girl who had posttraumatic
      stress disorder after the Great East Japan Earthquake. She received a dose of 60
      mg of tandospirone while taking 10 mg of tandospirone and 400 mg of valproic acid
      every day. She developed appetite loss, muscle weakness, muscle soreness, and
      general malaise on day 2, and laboratory data revealed a serum creatine
      phosphokinase level of 17,770 IU/L that reached a peak of 35,530 IU/L on day 4.
      Lactate dehydrogenase, aspartate aminotransferase, and alanine transaminase
      levels were also abnormal. After a fluid infusion was initiated and tandospirone
      was discontinued, most of her symptoms and abnormal laboratory data resolved
      within 10 days. CONCLUSION: This case suggests that careless high dosing of
      partial 5-HT1A receptor agonists is harmful to at-risk patients, such as
      adolescent patients with poor mental condition.

PMID- 30204601
TI  - Preface.

PMID- 30204600
TI  - Mean mid-arm circumference and blood pressure cuff sizes for US children,
      adolescents and adults: National Health and Nutrition Examination Survey, 2011
      2016.
AB  - BACKGROUND: Measuring blood pressure (BP) requires an appropriate BP cuff size
      given measured mid-arm circumference (mid-AC). OBJECTIVE: To provide mid-AC means
      and percentiles for US population aged more than 3 years and examine the
      frequency distribution of mid-AC cuffed by Baum and Welch Allyn cuff systems.
      PATIENTS AND METHODS: The 2011-2016 National Health and Nutrition Examination
      Survey, a cross-sectional survey, was used to estimate mean mid-AC (n=24 723).
      RESULTS: Mean mid-AC did not differ from 2011 to 2016 (31.0 vs. 31.3 cm, P>0.05).
      During 2011-2016, mean mid-AC was greater for males than females (32.0 vs. 30.4
      cm, P<0.001) and was largest among adults 40-49 years (34.0 cm). Non-Hispanic
      Black persons had the largest mean mid-AC (32.0 cm) and non-Hispanic Asian
      persons the smallest (28.4 cm). Increased BMI was associated with increased mean
      mid-AC for those 3-19 years (normal, 22.0 cm and obese, 31.5 cm, P<0.001) and
      more than 20 years (normal, 28.2 cm and obese, 37.8 cm, P<0.001). Among those
      aged 8-17 years, high BP status was associated with a larger mean mid-AC
      (normotensive 26.1 cm vs. high BP 28.2 cm, P=0.001). Among adults aged 18 years
      and older, hypertension status was associated with a larger mean mid-AC
      (normotensive 32.4 cm vs. hypertensive 34.2 cm, P<0.001). Among those aged 12-19
      years, 13.0% required a Baum large cuff (35-46.9 cm mid-AC) and 21.7% required a
      Welch Allyn large cuff (32-39.9 cm mid-AC). Among those aged more than 20 years,
      33.2% required a Baum large cuff, 48.2% required a Welch Allyn large cuff, 1.3%
      required a Baum extra-large cuff (44-66 cm mid-AC), and 9.5% required a Welch
      Allyn extra-large cuff (40-55 cm mid-AC). CONCLUSION: Currently, BP is obtained
      in clinic, pharmacy, home, and ambulatory setting using single or multiple cuffs.
      National Health and Nutrition Examination Survey mid-AC data should be considered
      for accurate cuffing avoiding cuff hypertension or hypotension.

PMID- 30204602
TI  - Management of Patients on Mechanical Circulatory Assist Devices During Noncardiac
      Surgery.

PMID- 30204603
TI  - When Your 35-Year-Old Patient has a Sternotomy Scar: Anesthesia for Adult
      Patients with Congenital Heart Disease Presenting for Noncardiac Surgery.

PMID- 30204604
TI  - Management of Severe Pulmonary Hypertensive Disease for Surgical and Nonsurgical
      Procedures.

PMID- 30204605
TI  - A Review of Perioperative Analgesic Strategies in Cardiac Surgery.

PMID- 30204606
TI  - Neurological Outcomes and Neuromonitoring in Cardiac Surgery.

PMID- 30204607
TI  - Surgical Approaches to Hypertrophic Cardiomyopathy and Implications for
      Perioperative Management.

PMID- 30204608
TI  - Where the Cath Lab and the Pump Room Meet: Anesthesia for Hybrid Procedures.

PMID- 30204609
TI  - Transcatheter Valve Procedures and the Anesthesiologist.

PMID- 30204610
TI  - Demystifying the EP Laboratory: Anesthetic Considerations for Electrophysiology
      Procedures.

PMID- 30204612
TI  - Road to a Genetic Model of Gelatinous Drop-Like Corneal Dystrophy.
AB  - Gelatinous drop-like corneal dystrophy (GDLD; OMIM: 204870) is an autosomal
      recessive Mendelian-inherited disease. Subepithelial amyloid deposition results
      in severe visual impairment. Its pathogenesis remains unknown. Identification of
      the responsible gene is a useful approach to investigating the pathogenesis of
      genetic diseases. Such an identification is also necessary for the creation of
      genetic models. For this purpose, our group performed positional cloning using
      homozygosity mapping. The results revealed that GDLD maps to the short arm of
      chromosome 1. Subsequent mutation analyses identified tumor-associated calcium
      signal transducer 2 (TACSTD2; former name, M1S1) as the gene responsible for
      GDLD. After identification of the gene, we examined the phylogenetical
      distribution of TACSTD2 in the genomes of vertebrates.

PMID- 30204613
TI  - Nuclear Medicine Therapy With 223Radium-dichloride for Osseous Metastases in
      Prostate Carcinoma.
AB  - Painful osseous metastasis resulting from castration-resistant prostate carcinoma
      is a common clinical problem. Historically, nuclear medicine offered several
      palliative beta-emitting radiopharmaceuticals targeting the skeleton with the
      goal of decreasing pain. However, these have largely been replaced by the alpha
      emitting agent radium (Ra). Ra received Food and Drug Administration approval in
      2013 for the treatment of metastatic castration-resistant prostate cancer with
      symptomatic bone metastases without visceral metastases. Ra offers an improved
      therapeutic profile due to its alpha-particle emissions resulting in a relatively
      higher linear energy transfer and lower particle range compared with beta
      emitters. Ra also has demonstrated to increase overall survival in patients and
      to delay adverse skeletal events. Running a successful clinical nuclear therapy
      program with Ra requires a multidisciplinary team approach and this article
      suggests an implementation strategy from the authors' institution. Potential new
      nuclear radiopharmaceuticals still under investigation offering the future
      possibility of radioligand therapy are also discussed briefly.

PMID- 30204614
TI  - Safety and Efficacy of Cabozantinib for Metastatic Nonclear Renal Cell Carcinoma:
      Real-world Data From an Italian Managed Access Program.
AB  - OBJECTIVE: The activity of cabozantinib in nonclear cell histologies has not been
      evaluated. MATERIALS AND METHODS: Data were collected across 24 Italian
      hospitals. Patients were aged 18 years and older with advanced nonclear cell
      renal cell carcinoma (RCC), with an Eastern Cooperative Oncology Group
      Performance Status 0 to 2, who had relapsed after previous systemic treatments
      for metastatic disease. Cabozantinib was administered orally at 60 mg once a day
      in 28 days cycles. Dose reductions to 40 or 20 mg were made due to toxicity.
      Adverse events (AEs) were monitored using CTCAE version 4.0. RESULTS: Seventeen
      patients were enrolled. Three (18%) patients were diagnosed type I papillary RCC,
      9 (53%) type II papillary, 3 (18%) chromophobe, and 2 (11%) with Bellini duct
      carcinoma. In total, 11 patients started with 60 mg. Six patients started a lower
      dose of 40 mg. Median progression-free survival was 7.83 months (0.4 to 13.4 mo),
      while median overall survival was not reached but 1-year overall survival was
      about 60%. Six patients (35%) experienced a partial response to treatment and 6
      patients (35%) showed a stable disease. In the remaining 5 (30%), we observed a
      progressive disease. Grade 3 and 4 AEs were observed in 41% of patients. Among 20
      patients, only 1 (6%) discontinued treatment due to AEs. Asthenia (41%), diarrhea
      (35%), aminotransferase increasing (35%), mucosal inflammation (35%), hand and
      foot syndrome (24%), and hypothyroidism (24%) were the most frequently AEs.
      CONCLUSIONS: Our data showed that, cabozantinib is a active and feasible
      treatment in patient with nonclear cell RCC.

PMID- 30204616
TI  - Caring for patients with chronic kidney disease.

PMID- 30204615
TI  - The Effects of Dynamic-range Automatic Gain Control on Sentence Intelligibility
      With a Speech Masker in Simulated Cochlear Implant Listening.
AB  - OBJECTIVES: "Channel-linked" and "multi-band" front-end automatic gain control
      (AGC) were examined as alternatives to single-band, channel-unlinked AGC in
      simulated bilateral cochlear implant (CI) processing. In channel-linked AGC, the
      same gain control signal was applied to the input signals to both of the two CIs
      ("channels"). In multi-band AGC, gain control acted independently on each of a
      number of narrow frequency regions per channel. DESIGN: Speech intelligibility
      performance was measured with a single target (to the left, at -15 or -30o) and a
      single, symmetrically-opposed masker (to the right) at a signal-to-noise ratio
      (SNR) of -2 decibels. Binaural sentence intelligibility was measured as a
      function of whether channel linking was present and of the number of AGC bands.
      Analysis of variance was performed to assess condition effects on percent correct
      across the two spatial arrangements, both at a high and a low AGC threshold.
      Acoustic analysis was conducted to compare postcompressed better-ear SNR,
      interaural differences, and monaural within-band envelope levels across
      processing conditions. RESULTS: Analyses of variance indicated significant main
      effects of both channel linking and number of bands at low threshold, and of
      channel linking at high threshold. These improvements were accompanied by several
      acoustic changes. Linked AGC produced a more favorable better-ear SNR and better
      preserved broadband interaural level difference statistics, but did not reduce
      dynamic range as much as unlinked AGC. Multi-band AGC sometimes improved better
      ear SNR statistics and always improved broadband interaural level difference
      statistics whenever the AGC channels were unlinked. Multi-band AGC produced
      output envelope levels that were higher than single-band AGC. CONCLUSIONS: These
      results favor strategies that incorporate channel-linked AGC and multi-band AGC
      for bilateral CIs. Linked AGC aids speech intelligibility in spatially separated
      speech, but reduces the degree to which dynamic range is compressed. Combining
      multi-band and channel-linked AGC offsets the potential impact of diminished
      dynamic range with linked AGC without sacrificing the intelligibility gains
      observed with linked AGC.

PMID- 30204617
TI  - The ABCs of chronic kidney disease.
AB  - Management of patients with chronic kidney disease has evolved since the last
      Kidney Disease Improving Global Outcomes clinical practice guideline was
      published in 2012. This article reviews the most recent guidelines, common
      management issues in primary care, kidney risk and outcome calculators, and over
      the-counter medications that may cause community-acquired acute kidney injury.

PMID- 30204618
TI  - A call to action on prediabetes.
AB  - Diabetes and prediabetes have become an epidemic in the United States. The keys
      to battling this public health challenge are effective screening and evidence
      based interventions. Studies show that intensive lifestyle interventions,
      medications, and weight loss surgery can reduce or delay new-onset type 2
      diabetes. This article reviews the steps clinicians can take to help patients
      stay ahead of this disease.

PMID- 30204619
TI  - The Placenta Accreta Spectrum: Epidemiology and Risk Factors.
AB  - The placenta accreta spectrum has become an important contributor to severe
      maternal morbidity. The true incidence is difficult to ascertain, but likely
      falls near 1/1000 deliveries. This number seems to have increased along with the
      rate of risk factors. These include placenta previa, previous cesarean section,
      use of assisted reproductive technologies, uterine surgeries, and advanced
      maternal age. With increased uterine conservation, previous retained placenta or
      placenta accreta have become significant risk factors. Understanding placenta
      accreta spectrum risk factors facilitates patient identification and safe
      delivery planning. Patients considering elective uterine procedures or delayed
      childbirth should consider the impact on peripartum morbidity.

PMID- 30204620
TI  - Antenatal Management of Placenta Accreta.
AB  - Predelivery diagnosis of placenta accreta, increta, and percreta (from here
      referred to as placenta accreta, unless otherwise noted) has increasingly created
      opportunities to optimize antenatal management. Despite the increased frequency
      of placenta accreta today, occurring in as many as 1 in 533 to 1 in 272
      deliveries, high-quality data are lacking for many aspects of antenatal
      management. This chapter will discuss antenatal management of, and risks faced
      by, women with suspected placenta accreta, a condition that most frequently
      requires a potentially morbid cesarean hysterectomy.

PMID- 30204621
TI  - Optic Perineuritis Due to Tuberculosis.
AB  - A 30-year-old man experienced subacute peripheral visual field loss with
      preserved central vision in his right eye. He was diagnosed with optic
      perineuritis due to tuberculosis. Optic perineuritis is an uncommon disorder and,
      at times, can be difficult to distinguish from optic neuritis. The
      differentiation can have significant impact on diagnostic testing and patient
      management.

PMID- 30204622
TI  - Phentermine: A Systematic Review for Plastic and Reconstructive Surgeons.
AB  - PURPOSE: Phentermine is the most prescribed antiobesity drug in America, with
      2.43 million prescriptions written in 2011. Case reports suggest there are
      anesthetic risks, such as refractory hypotension, involved with its perioperative
      use. Despite these risks and the frequency of phentermine use among plastic
      surgery patients, there are no published guidelines for the perioperative
      management of phentermine use in the plastic surgery literature. To address this
      patient safety issue, we performed a systematic review and provide management
      recommendations. METHODS: A systematic review of the pharmacology of phentermine
      and the anesthetic risks involved with its perioperative use was undertaken using
      the search engines PubMed/MEDLINE, EMBASE, and Scopus. RESULTS: A total of 251
      citations were reviewed, yielding 4 articles that discussed perioperative
      phentermine use and complications with anesthesia. One was a review article, 2
      were case reports, and 1 was a letter. Complications included hypotension,
      hypertension, hypoglycemia, hyperthermia, bradycardia, cardiac depression, and
      acute pulmonary edema. CONCLUSIONS: The relationship between phentermine and
      anesthesia, if any, is unclear. Hypotension on induction of general anesthesia is
      the most reported complication of perioperative phentermine use. Specifically,
      phentermine-induced hypotension may be unresponsive to vasopressors that rely on
      catecholamine release, such as ephedrine. Therefore, the decision to perform
      surgery, especially elective surgery, in a patient taking phentermine should be
      made with caution. Because of the half-life of phentermine, we recommend
      discontinuing phentermine for at least 4 days prior to surgery. This differs from
      the classic 2-week discontinuation period recommended for "fen-phen." The patient
      should be made aware of the increased risk of surgery, and a skilled
      anesthesiologist should monitor intraoperative blood pressure and body
      temperature for signs of autonomic derailment.

PMID- 30204623
TI  - Parental Distress and Stress in Association with Health-Related Quality of Life
      in Youth with Spina Bifida: A Longitudinal Study.
AB  - OBJECTIVE: This study examined associations between 3 distinct parent factors
      (parent personal distress, parenting stress, and spina bifida (SB)-specific
      parenting stress) and youth and parent proxy reports of youth health-related
      quality of life (HRQOL) over time. METHOD: Participants were recruited as part of
      a longitudinal study, and data were collected at 3 time points, spaced 2 years
      apart. Parents and youth completed questionnaires, and youth completed
      neuropsychological assessment tasks to determine youth intelligence quotient
      during home visits. RESULTS: Analyses revealed that higher levels of maternal SB
      specific parenting stress were related to lower levels of youth-reported HRQOL at
      time 1. Other parent factors were not associated with youth report of HRQOL at
      the earlier time points, although higher levels of maternal SB-specific parenting
      stress and paternal parenting stress were associated with lower levels of youth
      HRQOL at time 3. For mothers and fathers, increased parent personal distress,
      parenting stress, and SB-specific parenting stress were associated with decreased
      proxy report of youth HRQOL. Of these three parent factors, SB-specific parenting
      stress was consistently the most strongly associated with parent proxy-report of
      youth HRQOL. CONCLUSION: Parenting stress and distress are important targets for
      interventions, and these interventions may improve youth outcomes, especially as
      youth age. Future research is needed to identify other factors influencing youth
      HRQOL over time.

PMID- 30204625
TI  - The top 100 most-cited articles on 'Clubfoot'.
AB  - Clubfoot is an important aspect of pediatric orthopedics and is a readily
      prevalent condition presenting to orthopedic clinics worldwide. To identify
      landmark articles and important contributions to this field, we sought to do a
      citation analysis of the top 100 most-cited articles on clubfoot. Using the
      Scopus database and the search strategy 'Clubfoot', 'Clubfeet' OR 'Talipes
      Equinovarus', we identified 5753 articles. After filtering for relevant articles,
      the top 100 cited articles on clubfoot were retrieved for descriptive and
      statistical analysis. The most cited paper was 'Long-term results of treatment of
      congenital clubfoot' by S.J. Laaveg and I.V. Ponseti with 358 citations. The
      publication years ranged from 1969 to 2011. The USA was the most productive
      country in terms of research output, followed by the UK. Institution-wise, the
      University of Iowa contributed the most in terms of number of publications. The
      Journal of Pediatric Orthopaedics held the most number of articles. Most
      publications were level IV and level V studies. Although citation analysis has it
      flaws, this is a comprehensive list of the top 100 articles significantly
      affecting literature on clubfoot. On the basis our study, we conclude that there
      is marked deficiency of high-level articles with respect to the number of
      citations, and future researches need to cater to this question to produce high
      quality studies.

PMID- 30204624
TI  - Severity of ulnar deficiency and its relationship with lower extremity
      deficiencies.
AB  - To assess the characteristics of ulnar deficiency (UD) and their relationship to
      lower extremity deficiencies, we retrospectively classified 82 limbs with UD in
      62 patients, 55% of whom had femoral, fibular, or combined deficiencies. In
      general, UD severity classification at one level (elbow, ulna, fingers,
      thumb/first web space) statistically correlated with similar severity at another.
      Ours is the first study to show that presence of a lower limb deficiency is
      associated with less severe UD on the basis of elbow, ulnar, and thumb/first web
      parameters. This is consistent with the embryological timing of proximal upper
      extremities developing before the lower extremities.

PMID- 30204627
TI  - ACSM Clinician Profile.

PMID- 30204626
TI  - Expanded In-School Instructional Time and the Advancement of Health Equity: A
      Community Guide Systematic Review.
AB  - Expanded in-school instructional time (EISIT) may reduce racial/ethnic
      educational achievement gaps, leading to improved employment, and decreased
      social and health risks. When targeted to low-income and racial/ethnic minority
      populations, EISIT may thus promote health equity. Community Guide systematic
      review methods were used to search for qualified studies (through February 2015,
      11 included studies) and summarize evidence of the effectiveness of EISIT on
      educational outcomes. Compared with schools with no time change, schools with
      expanded days improved students' test scores by a median of 0.05 standard
      deviation units (range, 0.0-0.25). Two studies found that schools with expanded
      day and year improved students' standardized test scores (0.04 and 0.15 standard
      deviation units). Remaining studies were inconclusive. Given the small effect
      sizes and a lack of information about the use of added time, there is
      insufficient evidence to determine the effectiveness of EISIT on academic
      achievement and thus health equity.

PMID- 30204628
TI  - College Football: Conditioning Them to Death; Splenic Infarction: Keeping it in
      the Family.

PMID- 30204629
TI  - Should Children Be Running Ultramarathons?

PMID- 30204630
TI  - Adductor Insertion Avulsion Syndrome in a Collegiate Tennis Athlete: A Case
      Report.

PMID- 30204631
TI  - Cystic Adventitial Disease of the Popliteal Artery in an Adult Male Soccer
      Player: A Case Report.

PMID- 30204632
TI  - Myositis Ossificans in Sport: A Review.
AB  - Myositis ossificans is a benign, solitary, frequently self-limiting, ossifying
      soft-tissue mass encountered often in the active sporting population. Typically
      occurring within skeletal muscle - most often the brachialis, quadriceps and
      adductor muscle groups - lesions may arise with or without a traumatic history.
      The exact pathophysiology of these ossifying lesions is still poorly understood.
      Patients present with localized pain and swelling with loss of range of motion.
      Plain radiographs may not be able to detect early lesions, which allows for an
      expanded role of ultrasonography as an early screening modality, despite magnetic
      resonance imaging remaining the gold standard for imaging of soft tissue masses.
      Conservative treatment is implemented for most patients with excellent outcomes,
      with surgical excision being an option for persistent symptoms or progressive
      disease. Typically, athletes are able to progress to light activity at 2 to 3
      months, full activity by 6 months, and back to their preinjury level by 1 year.

PMID- 30204633
TI  - Return to Play After Thigh Muscle Injury: Utility of Serial Ultrasound in Guiding
      Clinical Progression.
AB  - Return to play after thigh muscle strain injury is difficult to predict and
      recurrent injury rates are high. There is currently no agreement on the optimal
      return to play protocol following muscle injury and utility of imaging is
      debated. Ultrasound has become an increasingly utilized imaging modality and
      offers several potential advantages for monitoring the return to play process
      following muscle injury. An ultrasound scanning protocol is presented which
      provides real-time guidance on muscle healing and may assist with identification
      of those athletes at risk of reinjury who otherwise appear clinically fit for
      return to play.

PMID- 30204634
TI  - Exercise for Athletes With Inflammatory Arthritis.
AB  - Advances in pharmacologic management of inflammatory conditions have allowed
      those living with these conditions to pursue fitness activities previously
      difficult due to functional limitations. With that said, many patients with
      inflammatory arthritis are still not active enough. In this article, we review
      specific exercise recommendations for a number of inflammatory conditions with a
      focus on overall health promotion and cardiovascular disease risk reduction,
      discuss exercise as an adjunct to pharmacologic disease management, and review
      potential risks of sport participation for athletes with inflammatory arthritis
      conditions.

PMID- 30204635
TI  - Shoulder Instability in the Overhead Athlete.
AB  - Shoulder instability encompasses a spectrum of disease ranging from subluxation
      to dislocation, and is typically associated with collision athletes such as
      wrestlers and football players. Instability, however, also can be the result of
      repetitive microtrauma, as seen in overhead athletes (baseball, tennis,
      volleyball, swimming). The presentation of instability can be subtle, and
      difficult to diagnose in the absence of an acute traumatic event without the
      proper suspicion, physical examination, and diagnostic evaluation. Overhead
      athletes present the unique challenge of requiring the glenohumeral joint to
      exceed its physiologic limits during competition; therefore, injury in this
      population can be devastating. Additionally, athletes who experience instability,
      regardless of treatment, require rehabilitation (including periscapular
      strengthening) to maximize strength of the surrounding musculature. Specifically
      they will require coordinated throwing programs, and gradual return to play
      protocols dependent on their sport. This article reviews the specific physiology,
      diagnosis, and treatment of shoulder instability in this population.

PMID- 30204636
TI  - Orbital Myxofibrosarcoma: Case Report and Review of Literature.
AB  - Myxofibrosarcoma is rarely found in the orbit, let alone as a primary orbital
      tumor. With this having only been previously reported 5 times in the literature,
      there is a very limited understanding of its presentation and course. Typical
      management involves surgical excision with or without postoperative radiotherapy.
      Low-grade malignancy, although rare to metastasize, still has a high rate of
      local recurrence and with each recurrence increases the risk of metastatic
      potential. With this in mind, analysis of each case is critical in better
      understanding the disease, and this case adds to the current literature.

PMID- 30204637
TI  - A Staged Procedure in the Treatment of Primary Lacrimal Sac Epithelial
      Malignancy: A Retrospective Cases Analysis.
AB  - PURPOSE: To determine the effect of a staged procedure in the treatment of
      primary lacrimal sac epithelial malignancy. METHODS: This is a retrospective case
      series of 18 consecutive patients with primary lacrimal sac epithelial malignancy
      treated at an orbital tumor referral center between 2002 and 2017. Study was
      conducted in compliance with the Declaration of Helsinki. All patients underwent
      biopsy of the mass to confirm the diagnosis pathologically. Chemotherapy
      concurrent with radiotherapy was delivered to the patients to reduce and concrete
      the tumor prior to surgery. En bloc resection of the lacrimal sac malignancy and
      nasolacrimal duct was followed. RESULTS: Eleven patients were male and 7 patients
      were female. The median follow-up time was 72.2 months. Nine patients had
      squamous cell carcinoma, 7 poorly differentiated carcinoma, 1 transitional cell
      carcinoma, and 1 adenoid cystic carcinoma. After chemotherapy and radiotherapy,
      the tumor volume was reduced significantly (p < 0.0001). En bloc resection of the
      lacrimal sac malignancy was performed in all patients with concurrent partial
      ethmoidectomy in 8 patients and medial maxillectomy in 5 patients. One patient
      (5.6%) suffered from adenoid cystic carcinoma died of metastatic disease. Two
      patients (11.1%) with local recurrence received reoperation, and 1 patient (5.6%)
      with pulmonary metastasis received gamma knife radiosurgery. These patients are
      alive with no evidence of tumor. Other patients are alive without evidence of
      disease at last follow up. No patient had new onset of lymph node enlargement
      during and after the treatment. CONCLUSIONS: The staged procedure is a promising
      method for the treatment of primary lacrimal sac epithelial malignancy with no
      postoperative lymph node metastasis.

PMID- 30204638
TI  - Resting-state functional connectivity as a biomarker of aggression in mild
      traumatic brain injury.
AB  - Mild traumatic brain injury (mTBI) can alter the structure of the brain and
      result in a range of symptoms, including elevated aggression. Neurological damage
      associated with mTBI is traditionally viewed as transient, yet a growing number
      of studies suggest long-lasting psychological and neurological changes following
      mTBI. However, research examining the neural basis of emotion processing in the
      chronic stage of mTBI recovery remains sparse. In the current study, we utilized
      resting state functional MRI to explore the association between default mode
      network connectivity and aggression in 17 healthy controls and 17 adults at least
      6 months post-mTBI. The association between within-network connectivity and
      aggression was examined using general linear models, controlling for the effects
      of depression. Increased connectivity between the right hippocampus and
      midcingulate cortex was associated with elevated aggression in adults with mTBI,
      but not in healthy controls. The results provide evidence for a link between
      intrinsic functional network disruptions and the manifestation of postconcussive
      symptoms within chronic stages of recovery following mTBI. These findings expand
      upon the current research, providing evidence for the use of resting state
      functional connectivity as a potential biomarker of postconcussive aggression in
      chronic mTBI.

PMID- 30204639
TI  - In Reply.

PMID- 30204640
TI  - To the Editor.

PMID- 30204641
TI  - Improving Charting Skills of Physicians in Monitored Practice.
AB  - INTRODUCTION: The Physician Enhancement Program (PEP) is an in-practice
      monitoring program for physicians with potential dyscompetency issues. One
      component of PEP is a monthly chart audit. The purpose of our study was to
      determine if physicians' charting skills improve through their participation in
      PEP. METHODS: The sample included physicians who participated in PEP for at least
      6 months regardless of specialization, age, or gender (n = 77). PEP chart audits
      evaluate seven different aspects of chart and care quality, including legibility,
      organization, history, assessment/formulation, treatment, physical examination,
      and overall chart quality. Each aspect of charting is scored on a Likert-type
      scale from a score of 1 to 9. We conducted pair-matched t tests of the mean item
      scores for the 1st versus 6th, 12th, 18th, and 24th month in PEP for all chart
      elements except legibility. We also compared the size of the paired differences
      by month 1 scores for overall chart quality mean score to determine if the
      magnitude of change varied by starting point. RESULTS: There was significant
      improvement (P < .002) across the 6 chart quality elements per physician at
      months 6, 12, 18, and 24. Physicians who started below Q1 for overall chart
      quality mean showed most improvement, whereas those who started above Q3 had
      insignificant change as they had little room to improve. DISCUSSION: PEP
      participants demonstrated improved charting skills for each chart quality element
      evaluated. PEP is an effective form of physician education resulting in physician
      behavior changes, especially for those physicians who need it the most.

PMID- 30204642
TI  - Evaluation of 18F-FDG PET/CT parameters for reflection of aggressiveness and
      prediction of prognosis in early-stage cervical cancer.
AB  - PURPOSE: The aim of this study was to investigate the value of five typical
      fluorine-18-fluorodeoxyglucose PET/computed tomography (CT) parameters (including
      SUVmax, SUVmean, SUVpeak, MTV and TLG) in the reflecting aggressiveness and
      predicting prognosis in patients with early-stage cervical cancer. PATIENTS AND
      METHODS: Our study enrolled 85 primary cervical cancer patients who underwent
      preoperative fluorine-18-fluorodeoxyglucose PET/CT scans. We investigated the
      association of five parameters derived from PET/CT with clinicopathological
      characteristics. Immunohistochemistry was utilized to evaluate the expression of
      glucose transporter protein-1 (GLUT-1), TP53-induced glycolysis and apoptosis
      regulator (TIGAR), and vascular endothelial growth factor (VEGF), and the
      correlation between PET/CT parameters and the expression of GLUT-1, TIGAR, and
      VEGF was analyzed. In addition, we also investigated the correlation between
      disease-free survival of cervical cancer patients and PET/CT parameters. RESULTS:
      The mean peak standardized uptake value (SUV)peak showed significant differences
      between all three International Federation of Gynecology and Obstetrics stages
      (P<0.001-0.032). The patients with lymph node metastasis had significantly higher
      SUVpeak, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) compared
      with those with the absence of lymph node metastasis (P=0.038, 0.024, and 0.010,
      respectively). All the five parameters showed an association with tumor size and
      cervical stromal invasion depth. Immunohistochemistry results indicated that the
      SUVpeak showed the highest association with the expression of GLUT-1, TIGAR, and
      VEGF (rs=0.705, P<0.001, rs=-0.466, P<0.001, rs=0.580, P<0.001, respectively) in
      these five parameters. The survival analysis showed that SUVpeak, MTV, and TLG
      were correlated with disease-free survival (P=0.042, P<0.001, and P=0.004,
      respectively). CONCLUSION: Early-stage cervical cancer with high SUVpeak may
      reflect more aggressive behavior, and SUVpeak, MTV, and TLG can be used to
      predict the prognosis of early-stage cervical cancer patients. It may help with
      the choice of individualized treatment options.

PMID- 30204644
TI  - Arthroscopic Treatment of Massive Posterosuperior Rotator Cuff Tears: A Critical
      Analysis Review.

PMID- 30204643
TI  - Impact of prompt gamma coincidence correction on absorbed dose estimation in
      differentiated thyroid cancer using 124I PET/CT imaging.
AB  - INTRODUCTION: Iodine-124 positron emission tomography/computed tomography (I
      PET/CT) is increasingly being used in the absorbed dose estimation in the
      radioiodine treatment of differentiated thyroid cancer (DTC). However, the
      produced prompt gamma coincidences (PGCs) associated with the I decay result in a
      bias in the absorbed dose estimation. The impact of a sinogram-based PGC
      correction approach on the absorbed dose estimation in I PET/CT DTC imaging is
      investigated. METHODS: I phantom and patient measurements were performed on a
      Siemens Biograph mCT PET/CT system. All images were reconstructed with (PGCon)
      and without PGC correction (PGCoff). The phantom contained seven spheres
      (diameters: 6.6-37 mm). The spheres and background compartment were filled with a
      I solution, resulting in a low (9.4 : 1) and a high sphere-to-background activity
      concentration ratio (750 : 1). Sphere recovery coefficient (RC) values were
      determined. In addition, the impact of PGC correction on measured lesion uptake
      and calculated lesion-absorbed dose was assessed for 66 lesions identified in 24
      DTC patients. RESULTS: PGC correction systematically increased sphere RC values
      up to 71% for the smallest spheres. For the patient data, PGC correction
      significantly increased both the measured I uptake (P<0.005) and the calculated
      lesion-absorbed dose (P=0.008) by ~3%. The percentage difference in the
      calculated lesion-absorbed dose ranged from -19% to 50%, showing that PGC
      correction had a variable and large impact for a few lesions. CONCLUSION: PGC
      correction resulted in significantly higher sphere RC values, I lesion uptake
      values and estimated lesion-absorbed doses.

PMID- 30204645
TI  - Management of Clavicle Fractures in Adolescents: A Critical Analysis Review.

PMID- 30204646
TI  - Reconstruction of Traumatic Central Slip Injuries: Technique Using a Slip of
      Flexor Digitorum Superficialis.
AB  - Multiple reconstruction techniques have been described for correction of
      boutonniere deformities including direct repair, central slip reconstruction,
      lateral band reconstruction, transverse retinacular ligament reconstruction,
      staged reconstruction, and extensor tenotomy. Each technique has been reported to
      have variable results with complications including capsular contracture, loss of
      proximal interphalangeal flexion, and residual deformity. We describe a surgical
      technique for central slip reconstruction using a slip of the flexor digitorum
      superficialis tendon through a bone tunnel.

PMID- 30204647
TI  - Effects of continuous theta-burst stimulation of the primary motor and secondary
      somatosensory areas on the central processing and the perception of trigeminal
      nociceptive input in healthy volunteers.
AB  - Noninvasive modulation of the activity of pain-related brain regions by means of
      transcranial magnetic stimulation promises an innovative approach at analgesic
      treatments. However, heterogeneous successes in pain modulation by setting
      reversible "virtual lesions" at different brain areas point at unresolved
      problems including the optimum stimulation site. The secondary somatosensory
      cortex (S2) has been previously identified to be involved in the perception of
      pain-intensity differences. Therefore, impeding its activity should impede the
      coding of the sensory component of pain intensity, resulting in a flattening of
      the relationship between pain intensity and physical stimulus strength. This was
      assessed using inactivating spaced continuous theta-burst stimulation (cTBS) in
      18 healthy volunteers. In addition, cTBS was applied on the primary motor cortex
      (M1) shown previously to yield moderate and variable analgesic effects, whereas
      sham stimulation at both sites served as placebo condition. Continuous theta
      burst stimulation flattened the relationship between brain activation and
      stimulus strength, mainly at S2, the insular cortex, and the postcentral gyrus
      (16 subjects analyzed). However, these effects were observed after inactivation
      of M1 while this effect was not observed after inactivation of S2. Nevertheless,
      both the M1 and the S2-spaced cTBS treatment were not reflected in the ratings of
      the nociceptive stimuli of different strengths (17 subjects analyzed),
      contrasting with the clear coding of stimulus strength by these data. Hence,
      while modulating the central processing of nociceptive input, cTBS failed to
      produce subjectively relevant changes in pain perception, indicating that the
      method in the present implementation is still unsuitable for clinical
      application.

PMID- 30204648
TI  - Positive allosteric modulators of nonbenzodiazepine gamma-aminobutyric acidA
      receptor subtypes for the treatment of chronic pain.
AB  - Chronic neuropathic pain may be caused, in part, by loss of inhibition in spinal
      pain processing pathways due to attenuation of local GABAergic tone. Nociception
      and nocifensive behaviors are reduced after enhancement of tonically activated
      extrasynaptic GABAAR-mediated currents by agonist ligands for delta subunit
      containing GABAARs. However, typical ligands that target delta subunit-containing
      GABAARs are limited due to sedative effects at higher doses. We used the spinal
      nerve ligation (SNL) and gp120 models of experimental neuropathic pain to
      evaluate compound 2-261, a nonbenzodiazepine site positive allosteric modulator
      of alpha4beta3delta GABAARs optimized to be nonsedative by selective activation
      of beta2/3-subunit-containing GABAARs over receptor subtypes incorporating beta1
      subunits. Similar levels of 2-261 were detected in the brain and plasma after
      intraperitoneal administration. Although systemic 2-261 did not alter sensory
      thresholds in sham-operated animals, it significantly reversed SNL-induced
      thermal and tactile hypersensitivity in a GABAAR-dependent fashion. Intrathecal 2
      261 produced conditioned place preference and elevated dopamine levels in the
      nucleus accumbens of nerve-injured, but not sham-operated, rats. In addition,
      systemic pretreatment with 2-261 blocked conditioned place preference from spinal
      clonidine in SNL rats. Moreover, 2-261 reversed thermal hyperalgesia and
      partially reversed tactile allodynia in the gp120 model of HIV-related
      neuropathic pain. The effects of 2-261 likely required interaction with the
      alpha4beta3delta GABAAR because 2-301, a close structural analog of 2-261 with
      limited extrasynaptic receptor efficacy, was not active. Thus, 2-261 may produce
      pain relief with diminished side effects through selective modulation of beta2/3
      subunit-containing extrasynaptic GABAARs.

PMID- 30204649
TI  - How variability in pain and pain coping relate to pain interference during
      multistage ultramarathons.
AB  - An important and substantial body of literature has established that maladaptive
      and adaptive coping strategies significantly impact pain-related outcomes. This
      literature, however, is based primarily on populations with painful injuries and
      illnesses. Little is known about coping in individuals who experience pain in
      other contexts and whether coping impacts outcomes in the same way. In an effort
      to better understand pain coping in such contexts, this study evaluated pain
      coping in ultramarathon runners, a population known to experience moderate levels
      of pain with minimal perceived negative effects. This study reports on pain
      coping in 204 entrants in 2016 RacingThePlanet multistage ultramarathon events.
      Participants provided data over 5 consecutive days on pain severity, pain
      interference, exertion, and coping. Results demonstrated that the study
      participants were more likely to use adaptive than maladaptive coping responses.
      However, maladaptive coping, but not adaptive coping, was positively associated
      with percent time spent thinking about pain and pain-related interference. Taken
      together, the study supports the idea that this high functioning group of
      individuals experiencing pain emphasizes the use of adaptive coping strategies
      over maladaptive strategies, reinforcing the perspective that such a pattern may
      be the most effective way to cope with pain. Within the group, however, results
      supported traditional patterns, such that greater use of maladaptive strategies
      was associated with greater pain-related interference, suggesting that optimizing
      pain coping may be critical to reducing factors that may interfere with
      ultramarathon performance.

PMID- 30204650
TI  - Customizing Functionality in an Electronic Health Record to Capture Value of
      Provider-Specific Services.

PMID- 30204651
TI  - NI2018: Fourteenth International Congress on Nursing Informatics.

PMID- 30204652
TI  - Electronic Charting During Simulation: A Descriptive Study.

PMID- 30204653
TI  - Oxygen Uptake, Heart Rate, and Lactate Responses for Continuous Forward Running
      and Stop-and-Go Running With and Without Directional Changes.
AB  - Bekraoui, N, Boussaidi, L, Cazorla, G, and Leger, L. Oxygen uptake, heart rate,
      and lactate responses for continuous forward running and stop-and-go running with
      and without directional changes. J Strength Cond Res XX(X): 000-000, 2018-The
      purpose of this study is to measure and quantify the differences for the gross
      oxygen uptake (V[Combining Dot Above]O2), heart rate (HR), and blood lactate
      ([LA]) responses to various modes of in-line running. Twelve healthy participants
      did an indirect continuous multistage field test to determine the maximal aerobic
      speed (MAS) before randomly performing in separate sessions 1 of the 3 running
      protocols at 3 intensities (60, 70, and 80% MAS) (a) in-line continuous running
      (IR), (b) fractioned running (FR) with stop and go every 20 m, and (c) 20-m
      shuttle run (SR). V[Combining Dot Above]O2 varied between 34.2 +/- 2.5 and 54.6
      +/- 5.4 ml.kg.min, HR between 141 +/- 14 and 184 +/- 9 b.min, and [LA] between
      4.2 +/- 0.8 and 6.6 +/- 0.9 mmol.L. In-line continuous running V[Combining Dot
      Above]O2 was lower than those of SR and FR at all intensities (p < 0.05).
      However, SR V[Combining Dot Above]O2 were higher than those of FR at 80% MAS
      only. Heart rate was similar in SR and FR but lower in IR at all intensities (p <
      0.05). No significant differences were recorded in [LA]. Because only V[Combining
      Dot Above]O2 was affected by the introduction of a 180 degrees  angle directional
      change (SR vs. FR) at 80% MAS, the use of HR to assess such activities at such
      intensities will result in underestimating workloads. This study offers new
      insights into V[Combining Dot Above]O2, HR, and [LA] associated with
      accelerations while running with and without directional changes at submaximal
      speeds.

PMID- 30204654
TI  - Comparison of 5vs5 Training Games and Match-Play Using Microsensor Technology in
      Elite Basketball.
AB  - Svilar, L, Castellano, J, and Jukic, I. Comparison of 5vs5 training games and
      match-play using microsensor technology in elite basketball. J Strength Cond Res
      XX(X): 000-000, 2018-The aim of this study was to compare the data obtained using
      microsensor technology in 2 types of 5vs5 training games-the regular-stop game
      (RSG) and the no-stop game (NSG)-and in match-play (MP) in elite basketball.
      Sixteen top-level basketball players were monitored during pre- and in-season
      periods (10 weeks). The variables included: player load, accelerations (ACC),
      decelerations (DEC), changes of direction (CoD), and jumps (JUMP)-all in both
      total (t) and high-intensity (h) relative values (i.e., per minute of play):
      PLmin, ACCmin, DECmin, CoDmin, and JUMPmin, respectively. Almost all variables
      showed trivial difference between MP and RSG. The only variable that showed small
      difference was tACCmin (MP > RSG). In case of RSG vs. NSG, 3 variables showed
      trivial difference-tACCmin, hACCmin, and hDECmin, 3 (i.e., hCODmin, tDECmin, and
      PLmin) small differences, and 3 (tCoDmin, tJUMPmin, and hJUMPmin) moderate
      differences (NSG > RSG). In MP vs. NSG, 2 variables (hCoDmin and tACCmin) showed
      trivial differences; variable hDECmin showed small difference, whereas the other
      5 variables (tCoDmin, tJUMPmin, hJUMPmin, tDECmin, and PLmin) showed moderate
      difference (NSG > MP). Only one variable, hACCmin, showed moderate difference,
      when MP > NSG. The main conclusion of the study was that by introducing some
      constraints into 5vs5 tasks, the coaching staff could elicit higher physical
      demands than those occurring in MP. By understanding the differences in demands
      of NSG, RSG, and MP, coaches in elite basketball can improve their system of
      training drills selection, especially when looking for optimal short-term
      tapering approach, leading up to the game day.

PMID- 30204655
TI  - Familiarization With Airflow-Restriction Mask During Resistance Exercise: Effect
      on Tolerance and Total Volume.
AB  - Teodoro, CL, Gaspari, AF, Berton, R, Barbieri, JF, Silva, M, Castano, LAA,
      Guimaraes, P, and Moraes, AC. Familiarization with airflow-restriction mask
      during resistance exercise: Effect on tolerance and total volume. J Strength Cond
      Res XX(X): 000-000, 2018-This study investigated whether familiarization with the
      airflow-restriction mask (AIRfr) increases tolerance and avoids negative effects
      on performance of resistance exercise (RE). Ten resistance-trained male subjects
      performed a familiarization session (FAM), followed by 2 testing sessions, with
      the AIRfr and without airflow restriction (SHAM) in a counterbalanced and
      randomized cross-over design. The FAM was performed with the same number of sets,
      load, and level of airflow-restriction as the AIRfr experimental session. Each
      session consisted of 4 sets of the leg press exercise with 70% 1 repetition
      maximum until voluntary failure and a 90-second rest interval between sets.
      During the FAM, 4 of the 10 subjects expressed some intolerance to the use of
      airflow restriction. Total volume was lower in the FAM than in the AIRfr (p =
      0.01) and the SHAM (p = 0.02), whereas no differences were observed between the
      AIRfr and the SHAM (p = 0.90). The first use of the AIRfr may not be well
      tolerated by all subjects. However, a familiarization session with the AIRfr
      avoids negative interferences in the total volume during RE.

PMID- 30204656
TI  - Waist Circumference and Waist-to-Hip Ratio in Law Enforcement Agency Recruits:
      Relationship to Performance in Physical Fitness Tests.
AB  - Lockie, RG, Ruvalcaba, TR, Stierli, M, Dulla, JM, Dawes, JJ, and Orr, RM. Waist
      circumference and waist-to-hip ratio in law enforcement agency recruits:
      relationship to performance in physical fitness tests. J Strength Cond Res XX(X):
      000-000, 2018-Law enforcement agencies (LEAs) use tests to assess recruit
      physical fitness. Body fat can influence test performance but is difficult to
      measure during academy because of time, equipment constraints, and instructor
      knowledge. This study examined relationships between waist circumference (WC) and
      waist-to-hip ratio (WHR), practical measures of fat distribution, and fitness
      test performance. Retrospective analysis of 267 LEA recruits (age: ~28 years;
      height: ~1.73 m; and body mass: ~80 kg; 219 males and 48 females) was conducted.
      The tests included: WC and WHR; grip strength; push-ups, sit-ups, and arm
      ergometer revolutions in 60 seconds; vertical jump (VJ); medicine ball throw; 75
      yd pursuit run (75PR); and multistage fitness test (MSFT) shuttles. Partial
      correlations, controlling for sex, calculated relationships between WC, WHR, and
      the fitness tests. Recruits were split into quartile groups (based on the sample
      size) for WC and WHR (group 1 had the lowest WC and WHR; and group 4 the
      highest). A 1-way multivariate analysis of variance, with sex as a covariate and
      Bonferroni post hoc, compared between-group test performance. A greater WC
      related to lesser push-up, sit-up, VJ, 75PR, and MSFT performance (p <= 0.024).
      When recruits were split into WC groups, group 4 had lesser performance in push
      ups, sit-ups, VJ, and the 75PR compared with all groups (p <= 0.038). When split
      into WHR groups, group 4 performed less push-ups than group 1, less MSFT shuttles
      than group 3, and had a lower VJ compared with all groups (p <= 0.042). Recruits
      with a greater WC tended to have poorer fitness test performance.

PMID- 30204657
TI  - Range of Motion Adaptations in Powerlifters.
AB  - Gadomski, SJ, Ratamess, NA, and Cutrufello, PT. Range of motion adaptations in
      powerlifters. J Strength Cond Res XX(X): 000-000, 2018-The aim of this study was
      to investigate range of motion (ROM) and training patterns in powerlifters. Upper
      and lower-extremity passive ROMs were assessed through goniometry in 15 male
      powerlifters (35.3 +/- 13.7 years) and 15 age-matched controls (34.9 +/- 14.6
      years). The Apley scratch test and modified Thomas test were used to assess ROM
      across multiple joints. Training frequency, stretching frequency, and exercise
      selection were recorded using questionnaires. Passive glenohumeral (GH)
      extension, internal rotation, and external rotation ROM were significantly
      decreased in powerlifters (p < 0.050). Powerlifters displayed decreased ROM in
      the Apley scratch test in both dominant (p = 0.015) and nondominant (p = 0.025)
      arms. However, knee extension angle was markedly improved in powerlifters (20.3
      +/- 7.3 degrees ) compared with controls (29.9 +/- 6.2 degrees ; p < 0.001).
      Bench press and bench press variations accounted for 74.8% of all upper-body
      exercises, whereas back squat and deadlift accounted for 79.7% of all lower-body
      exercises in powerlifters' training programs. To determine whether existing ROM
      adaptations were seen in elite powerlifters, the powerlifting cohort was split
      into 3 groups based on Wilks score: <400 (low), 400-500 (intermediate), and >500
      (high). GH ROM limitations were more pronounced in elite powerlifters (Wilks
      >500), who had more powerlifting experience (p = 0.048) and greater lean body
      mass (p = 0.040). Overall, powerlifters displayed decreased GH ROM, but increased
      hamstring ROM, after training programs that were heavily focused on the bench
      press, back squat, and deadlift.

PMID- 30204658
TI  - Human Parechovirus 3 in Infants: Expanding our Knowledge of Adverse Outcomes.
AB  - BACKGROUND: Human parechovirus particularly genotype 3 (HPeV3), is an emerging
      infection affecting predominantly young infants. The potential for neurological
      sequelae in a vulnerable subset is increasingly apparent. A review of two
      epidemics of HPeV infection in 2013 and in 2015 in Queensland, Australia was
      undertaken, with an emphasis on identifying adverse neurodevelopmental outcome.
      METHODS: All hospitalized cases with laboratory-confirmed HPeV infection between
      October 2013 June 2016 were identified. Clinical, demographic, laboratory and
      imaging data were collected and correlated with reported developmental outcome.
      RESULTS: Laboratory-confirmed HPeV infections were identified in 202 patients
      across 25 hospitals; 86.6% (n=175) were younger than 3 months 16.3% (n=33)
      received intensive care admission. Of 142 cerebrospinal fluid (CSF) samples which
      were HPeV PCR positive, all 89 isolates successfully genotyped were HPeV3.
      Clinical information was available for 145 children; 53.1% (n=77) had follow up
      from a paediatrician, of whom 14% (n=11) had neurodevelopmental sequelae, ranging
      from hypotonia and gross motor delay to spastic quadriplegic cerebral palsy and
      cortical visual impairment. Of 15 children with initially abnormal brain magnetic
      resonance imaging (MRI), 47% (n=7) had neurodevelopmental concerns, the remainder
      had normal development at follow up between 6 - 15 months of age. CONCLUSIONS:
      This is the largest cohort of HPeV3 cases with clinical data and paediatrician
      assessed neurodevelopmental follow up to date. Developmental concerns were
      identified in 11 children at early follow-up. Abnormal MRI during acute infection
      did not specifically predict poor neurodevelopmental in short-term follow-up.
      Continued follow-up of infants and further imaging correlation is needed to
      explore predictors of long term morbidity.

PMID- 30204659
TI  - Hepatitis C Genotype 4 Virus NS3 and NS5A resistance Associated Substitutions in
      a 16 Year-Old Adolescent Failing Ombitasvir/Paritaprevir/Ritonavir Plus
      Ribavirin.
AB  - Pre-existence and appearance of resistance associated substitutions limit the
      efficacy of direct acting antivirals in treatment of hepatitis C. This is the
      first case report of an adolescent with chronic hepatitis C virus genotype 4
      infection and cirrhosis who failed treatment with
      ombitasvir/paritaprevir/ritonavir and ribavirin. Resistance analysis showed
      baseline resistance associated substitutions M28V and Y93C and emergent D168H.

PMID- 30204660
TI  - Nevirapine Concentrations During the First Month of Life And Maternal Efavirenz
      Washout in High Risk HIV-Exposed Infants Receiving Triple Antiretroviral
      Prophylaxis.
AB  - BACKGROUND: Triple-drug infant antiretroviral prophylaxis containing nevirapine
      (NVP) is increasingly used to prevent HIV transmission among neonates at high
      risk of HIV-infection. Our aim was to describe NVP concentration from birth
      through the first month of life. METHODS: High-risk HIV-exposed neonates were
      enrolled in a prospective cohort in Thailand. High-risk neonates, defined as
      maternal HIV RNA >50 copies/mL prior to delivery or mother received
      antiretroviral treatment (ART) for <12 weeks before delivery. Neonates received
      zidovudine (ZDV, 4 mg/kg) and lamivudine (3TC, 2 mg/kg) twice daily, plus NVP (4
      mg/kg) once daily (no lead-in) from birth to 6 weeks of life. Infant plasma
      samples were collected at 1, 2, 14 or 2, 7, 28 days of life. NVP trough
      concentrations (C24) were estimated using a population pharmacokinetic model and
      target C24 was >=0.1 mg/L. 'Washout' efavirenz (EFV) concentrations were assessed
      in infants whose mother received EFV-based ART. RESULTS: A total of 48 infants
      were included: 25 (52%) were male and 12 (25%) were preterm (gestational age (GA)
      34-37 weeks). Median (IQR) predicted NVP C24 were 1.34 mg/L (1.13-1.84), 2.24
      (2.00-2.59), 2.78 (2.61-3.12), 2.20 (1.86-2.44), and 0.81 (0.58-0.98) on days 1,
      2, 7, 14, and 28 of life, respectively. NVP C24 was not significantly different
      between term and preterm infants. All infants maintained NVP C24 >=0.1 mg/L. EFV
      via placental transfer remained detectable in infants up to 7 days of life.
      CONCLUSIONS: NVP 4 mg/kg daily from birth provided adequate prophylactic
      concentrations during the first month of life in high-risk HIV-exposed neonates.

PMID- 30204661
TI  - Taurolidine-Citrate Line Locks Prevent Recurrent Central Line Associated
      Bloodstream Infection in Pediatric Patients.
AB  - This study describes a successful, targeted intervention in central venous access
      device routine care, to decrease central line associated bloodstream infection
      (CLABSI). Taurolidine-Citrate locks significantly reduced the rate of CLABSI,
      particularly Gram negative organisms without adverse events.

PMID- 30204662
TI  - Rate of Recurrence of Adverse Events Following Immunization: Results of 19 Years
      of Surveillance Ii Quebec, Canada.
AB  - BACKGROUND: While adverse events following immunization (AEFI) are frequent,
      there are limited data on the safety of reimmunizing patients who had a prior
      AEFI. Our objective was to estimate the rate and severity of AEFI recurrences.
      METHODS: We analyzed data from the AEFI passive surveillance system in Quebec,
      Canada that collects information on reimmunization of patients who had a prior
      AEFI. Patients with an initial AEFI reported to the surveillance system between
      1998 and 2016 were included. Rate of AEFI recurrence was calculated as: number of
      patients with recurrence/ total number of patients reimmunized. RESULTS: Overall,
      1350 patients were reimmunized, of which 59% were less than 2 years old. The AEFI
      recurred in 16% (215/1350) of patients, of whom 18% (42/215) rated the recurrence
      as more severe than the initial AEFI. Large local reactions extending beyond the
      nearest joint and lasting 4 days or more had the highest recurrence rate (67%,
      6/9). Patients with hypotonic hyporesponsive episodes had the lowest rate of
      recurrence (2%, 1/50). Allergic-like events recurred in 12% (76/659) of patients
      but none developed anaphylaxis. Of 33 patients with seizures following measles
      mumps rubella with/without varicella vaccine, none had a recurrence. Compared
      with patients with non-serious AEFIs, those with serious AEFIs were less often
      reimmunized (60% versus 80%, rate ratio: 0.8, 95% confidence interval 0.66 to
      0.86). CONCLUSION: Most patients with a history of mild or moderate AEFI can be
      safely reimmunized. Additional studies are needed in patients with serious AEFIs
      who are less likely to be reimmunized.

PMID- 30204663
TI  - Context revisited: situations beyond our kin.

PMID- 30204664
TI  - Pharmacotherapy for the pseudobulbar affect in individuals who have sustained a
      traumatic brain injury: a systematic review protocol.
AB  - REVIEW OBJECTIVE/QUESTION: The objective of this systematic review is to
      synthesize current evidence on the effectiveness of pharmacotherapy as compared
      to all comparators for the management of pseudobulbar affect in adults 16 years
      and over who have sustained a traumatic brain injury. The specific review
      question is: What is the effectiveness of pharmacotherapy for the management of
      pseudobulbar affect in adults 16 years and over who have sustained a traumatic
      brain injury?

PMID- 30204665
TI  - Perceptions and experiences of nurses and midwives in continuing professional
      development: a systematic review protocol.
AB  - REVIEW QUESTION/OBJECTIVE: The objective of this systematic review is to explore
      the perceptions and experiences of nurses and midwives in undertaking continuing
      professional development.

PMID- 30204666
TI  - Occupational therapy interventions in child and adolescent mental health: a mixed
      methods systematic review protocol.
AB  - REVIEW QUESTION/OBJECTIVE: The question of this review is: what is the
      effectiveness of occupational therapy on participation in everyday occupations
      for children and adolescents with mental health difficulties? The objective is to
      identify the evidence of occupational therapy interventions that are occupation
      based and/or occupation-focused.The quantitative component of the review will
      consider studies that evaluate the effectiveness of occupation-based and/or
      occupation-focused interventions; the qualitative component of this review will
      consider studies that investigate the experiences of these interventions, and the
      textual component of this review will consider publications that describe these
      occupational therapy interventions.The quantitative objective is to identify the
      effectiveness of occupational therapy on participation in everyday occupations
      for children and adolescents with mental health difficulties.The qualitative
      objective is to identify the experiences of occupational therapy interventions on
      participation for children and adolescents with mental health difficulties in
      everyday activities.The textual objective is to identify narrative, text and
      opinion about occupational therapy interventions on the participation of children
      and adolescents mental health that have yet to be subjected to empirical
      analysis.

PMID- 30204667
TI  - Experiences of women living with infertility in Africa: a qualitative systematic
      review protocol.
AB  - REVIEW QUESTION: What are the experiences of women living with infertility in
      Africa?

PMID- 30204668
TI  - Effectiveness of case management performed by nurses for blood pressure control
      in adults with hypertension: a systematic review protocol.
AB  - REVIEW QUESTION/OBJECTIVE: The question of this review is: what is the
      effectiveness of nurse case management in primary healthcare for improving blood
      pressure, in adults over 18 years with hypertension?The objective of this review
      is to synthesize the best available evidence regarding the effectiveness of nurse
      case management in primary healthcare, compared to usual care, in improving blood
      pressure in adults over 18 years with hypertension.

PMID- 30204669
TI  - Effectiveness of corneal abrasion prevention interventions for adults undergoing
      general anesthesia for more than one hour: a systematic review protocol.
AB  - REVIEW QUESTION: The question of this review is: what is the effectiveness of eye
      lubrication, tape and/or a combination of these interventions in preventing
      corneal abrasions in adult patients aged 18 and over undergoing general
      anesthesia for more than one hour?

PMID- 30204670
TI  - Effectiveness of decision aids for smoking cessation in adults: a quantitative
      systematic review.
AB  - OBJECTIVE: The objective of the review was to determine the effectiveness of the
      use of decision aids to facilitate the shared decision-making process between a
      person and a healthcare provider on smoking cessation rates, knowledge of smoking
      cessation methods and decisional quality. INTRODUCTION: The tobacco epidemic is
      one of the biggest health threats in the world, and it is the single most
      important preventable cause of disease. In the smoking cessation process, people
      move through different stages in their readiness to quit. Healthcare providers
      are well positioned to impact smoking cessation, however, challenges continue to
      exist. Using decision aids in the smoking cessation decision-making process may
      be one means in moving people toward the decision to quit smoking. INCLUSION
      CRITERIA: The review considered randomized controlled trials and quasi
      experimental studies which included adults, 18 years and over, who smoke tobacco
      products. The intervention of interest was implementation of decision aids to
      promote shared decision-making related to smoking cessation. The comparator was
      usual care without the use of decision aids. Outcomes of interest were smoking
      abstinence, smoking quit attempts, knowledge of smoking cessation methods and
      decisional quality. METHODS: A comprehensive search was undertaken to locate
      relevant published and unpublished quantitative English language studies from the
      inception of each database searched through July 30, 2017. Databases searched
      included: CINAHL, Cochrane Central Register of Controlled Trials, Embase,
      PsycINFO and PubMed. A search of gray literature was also performed. Titles and
      abstracts were screened by two independent reviewers for assessment against the
      inclusion criteria. Studies meeting the inclusion criteria were retrieved in full
      and assessed in detail against the inclusion criteria by two independent
      reviewers. Two reviewers independently evaluated the included studies for
      methodological quality using critical appraisal tools from the Joanna Briggs
      Institute (JBI). Data related to the methods, participants, interventions and
      findings were extracted by two independent reviewers using a standardized data
      extraction tool from JBI. Due to clinical and methodological heterogeneity in the
      interventions and outcome measures of the included studies, statistical meta
      analysis was not possible. Results have been presented in narrative form.
      RESULTS: Eight papers representing seven unique studies evaluating smoking
      cessation decision aids were included. Of the six studies that measured
      abstinence, only two had positive findings, with one reaching statistical
      significance. The fours studies that measured quit attempts all demonstrated a
      trend toward an increase in the number of quit attempts, with one study reaching
      statistical significance. Four of the five studies that measured knowledge
      reported an initial increase in the knowledge of smoking cessation methods, with
      two studies reaching statistical significance. Two of the three studies that
      measured decisional quality showed an improvement in decisional quality after use
      of the decision aid, with one study reaching statistical significance.
      CONCLUSIONS: The evidence suggests that decision aids may be effective in
      increasing smoking cessation knowledge and decisional quality while increasing
      quit attempts. There is, however, inconclusive evidence to support the definitive
      effectiveness of decision aids for long term and sustained smoking cessation.

PMID- 30204671
TI  - Effects of pharmacist prescribing on patient outcomes in the hospital setting: a
      systematic review.
AB  - OBJECTIVE: The objective of the review was to synthesize the best available
      evidence on the safety and effectiveness of pharmacist prescribing on patient
      outcomes in patients who present to hospital. INTRODUCTION: Pharmacist
      prescribing is legal in many countries. Different models of prescribing include
      dependent, collaborative and independent. Existing reviews of pharmacist
      prescribing focus on studies in the community setting, or both community and
      hospital settings. Other reviews focus on descriptions of current practice or
      perspectives of clinicians and patients on the practice of pharmacist
      prescribing. A systematic review on the effects of pharmacist prescribing on
      patient outcomes in the hospital has not been previously undertaken and is
      important as this practice can help ease the burden on the healthcare system.
      INCLUSION CRITERIA: Studies with controlled experimental designs comparing
      pharmacist prescribing to medical prescribing in the hospital setting were
      included in the review. Primary outcomes of interest included clinical outcomes
      such as therapeutic failure or benefit, adverse effects, and morbidity or
      mortality. Secondary outcomes included error rates in prescriptions, medication
      omissions on the medication chart, time or proportion of International Normalized
      Ratios in therapeutic range, time to reach therapeutic range, and patient
      satisfaction. METHODS: A comprehensive three-step search strategy was utilized.
      The search was conducted in January 2017 in eight major databases from database
      inception. Only studies in English were included. The recommended Joanna Briggs
      Institute approach to critical appraisal, study selection and data extraction was
      used. Narrative synthesis was performed due to heterogeneity of the studies
      included in the review. RESULTS: The 15 included studies related to dependent and
      collaborative prescribing models. In four studies that measured clinical
      outcomes, there was no difference in blood pressure management between
      pharmacists and doctors while patients of pharmacist prescribers had better
      cholesterol levels (mean difference in low density lipoprotein of 0.4 mmol/L in
      one study and 1.1 mmol/L in another; mean difference in total cholesterol of 1.0
      mmol/L) and blood sugar levels (mean difference of fasting blood sugar levels of
      15 mg/dL, mean difference of glycosylated hemoglobin of 2.6%). In two studies,
      pharmacists were better at adhering to warfarin dosing nomograms than doctors
      (average of 100% versus 62% compliance). In six studies, when prescribing
      warfarin according to dosing nomograms, equivalent numbers or more patients were
      maintained in therapeutic range by pharmacist prescribers compared to doctors.
      The incidence of adverse effects related to anticoagulant prescribing was similar
      across arms but all six studies were underpowered to detect this outcome. Three
      studies found that pharmacist prescribers made less prescribing errors (20 to 25
      times less errors) and omissions (three to 116 times less omissions) than doctors
      when prescribing patients' usual medications on admission to hospital or in the
      preoperative setting. Two studies reported that patients were as satisfied with
      the services provided by pharmacist prescribers as with doctors. CONCLUSIONS:
      This review provides low to moderate evidence that pharmacists can prescribe to
      the same standards as doctors. Pharmacists are better at adhering to dosing
      guidelines when prescribing by protocol and make significantly less prescribing
      errors when charting patients' usual medications on admission to hospital.

PMID- 30204672
TI  - Management of peripherally inserted central catheter use in an intensive care
      unit of a teaching hospital in Brazil: a best practice implementation project.
AB  - OBJECTIVE: This project aimed to promote evidence-based practice in the
      management of peripherally inserted central venous catheters (PICCs) in pediatric
      and adult patients in an intensive care unit (ICU). INTRODUCTION: A PICC provides
      secure vascular access to medication, blood and nutrition administration.
      However, their use in the ICU is limited. Gaps in training and education in the
      use of these catheters are barriers to improving practice and safety. METHODS:
      The project was conducted in an ICU of a cardiology teaching hospital in Sao
      Paulo, Brazil. The Joanna Briggs Institute Practical Application of Clinical
      Evidence System and Getting Research into Practice audit tools were used. A
      baseline audit of the management of PICCs in pediatric and adult patients was
      conducted, with a sample size of 22 patients and 180 nursing staff. After an
      educational program, a follow-up audit involving 14 patients and 180 nursing
      staff was conducted using the same audit criteria. RESULTS: The baseline audit
      indicated that PICC management concerning flushing had poor compliance of 2-20%.
      The results of the criteria related to the change in administration sets,
      including secondary sets and add-on devices, had better results, with moderate
      (65%) to high (100%) compliance. The follow-up audit showed improvement in all 10
      criteria. Criteria related to flushing achieved 83% to 89% compliance; criteria
      related to dressing and change of administration sets achieved 100% compliance.
      CONCLUSIONS: Increased compliance with evidence-based best practices was achieved
      in all assessed audit criteria. The criteria that reached the highest compliance
      with best practice recommendations were related to the prevention of bloodstream
      infection and loss of the PICC due to obstruction. Future audits are planned to
      ensure sustainability.

PMID- 30204673
TI  - Prevention of venous thromboembolism in postoperative abdominal patients: a best
      practice implementation project.
AB  - OBJECTIVES: This project's aim was to ensure that venous thromboembolism
      assessment was performed accurately, and that adequate prophylaxis was followed
      up, resulting in a decrease in the incidence of venous thromboembolism
      postoperatively and enhancing recovery after surgery. INTRODUCTION: Venous
      thromboembolism (VTE), which includes deep venous thrombosis and pulmonary
      embolism, is a leading cause of morbidity and mortality in hospitalized patients.
      Evidence suggests that the majority of hospital patients are at risk for VTE, but
      the prophylaxis recommended for their risk factors are not adequately utilized.
      Venous thromboembolism prevention is primarily based on an adequate risk
      stratification. METHODS: A baseline audit on VTE prevention utilizing the Joanna
      Briggs Institute Practical Application of Clinical Evidence System program was
      undertaken and involved 21 nurses and 30 patients. An intervention including VTE
      education, clinical practice and prophylaxis was conducted, following which a
      post-implementation re-audit was undertaken. RESULTS: The baseline audit results
      showed that four audit criteria results were found to under 30%, which indicated
      poor compliance with the current evidence. After implementing the strategies,
      including education, VTE video, etc., there was a huge improvement, with most of
      the audit criteria achieving 100% compliance. CONCLUSIONS: Overall the project
      achieved a significant improvement in evidence-based practice in the prevention
      of VTE, implemented in two wards. Sustaining best practice should be planned for
      the future.

PMID- 30204674
TI  - Erratum to: Multidisciplinary management of diabetic kidney disease: a systematic
      review and meta-analysis.

PMID- 30204675
TI  - Erratum to: Effectiveness and harms of pharmacological interventions in the
      treatment of delirium in adults in intensive care units post cardiac surgery: a
      systematic review protocol.

PMID- 30204677
TI  - Incision Choices in Nipple-Sparing Mastectomy: A Comparative Analysis of Outcomes
      and Evolution of a Clinical Algorithm.
AB  - BACKGROUND: Nipple-sparing mastectomy allows for preservation of the entire
      nipple-areola complex using various incision patterns. Reconstructive trends and
      overall risk associated with these diverse nipple-sparing mastectomy incisions
      have yet to be fully elucidated. METHODS: All nipple-sparing mastectomies from
      2006 to 2017 were identified; outcomes were stratified by type of mastectomy
      incision: lateral or vertical radial, inframammary fold, Wise pattern, previous,
      and periareolar. RESULTS: A total of 1207 nipple-sparing mastectomies were
      included for final analysis. Of these, 638 (52.9 percent) used an inframammary
      fold incision, 294 (24.4 percent) used a lateral radial incision, 161 (13.3
      percent) used a vertical radial incision, 60 (5.0) used a Wise pattern incision,
      35 (2.9 percent) used a previous incision, and 19 (1.6 percent) used a
      periareolar incision. The groups were heterogeneous and differed significantly
      with regard to various factors, including age (p < 0.001), body mass index (p <
      0.001), reconstruction modality (p < 0.001), and others. In crude multivariate
      logistic regression analysis, vertical radial (16.1 percent) and inframammary
      fold incisions (21.0 percent) were associated with lower overall complication
      rates. In a reduced multivariate logistic regression model, inframammary fold
      incisions (p = 0.001) emerged as significantly protective of overall
      complications after controlling all variables. CONCLUSIONS: Nipple-sparing
      mastectomy may be safely performed using various mastectomy incisions, each with
      unique advantages and limitations. Overall, inframammary fold incisions appear to
      be associated with the lowest risk, whereas Wise pattern incisions may increase
      risk. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

PMID- 30204678
TI  - Unplanned Emergency Department Visits within 30 Days of Mastectomy and Breast
      Reconstruction.
AB  - BACKGROUND: Unplanned emergency department visits are often overlooked as an
      indicator of care quality. The authors' objectives were to (1) determine the rate
      of 30-day emergency department visits following mastectomy with or without
      immediate reconstruction, (2) perform a risk analysis of potential factors
      associated with emergency department return, and (3) assess for potentially
      preventable visits with a focus on returns for pain. METHODS: Using the
      Healthcare Cost and Utilization Project data, the authors identified adult women
      who underwent mastectomy with or without reconstruction. Multivariable logistic
      regression was performed to evaluate risk of unplanned emergency department
      visits. The authors identified and sorted diagnostic codes to investigate why
      patients were seeking emergency department care. In addition, the authors
      performed a subgroup analysis on patients returning with a pain-related diagnosis
      to evaluate risk. RESULTS: Of 159,275 cases of mastectomy with or without
      immediate reconstruction, 4917 (3.1 percent) experienced an unplanned return to
      the emergency department within 30 days of operation. A substantial proportion of
      those who returned (23 percent) presented with a pain-related diagnosis. Only 0.9
      percent of cases with a 30-day emergency department return were readmitted.
      CONCLUSIONS: Numerous patients return to the emergency department within 30 days
      of mastectomy with or without immediate reconstruction. There is a need for
      policy makers and physicians to implement strategies to reduce discretionary
      emergency department use, specifically among younger or publicly insured
      patients. Combining unplanned emergency department visits with readmission rates
      as a care quality indicator warrants consideration. CLINICAL QUESTION/LEVEL OF
      EVIDENCE: Risk, III.

PMID- 30204676
TI  - Immediate Implant-Based Breast Reconstruction with Acellular Dermal Matrix: A
      Comparison of Sterile and Aseptic AlloDerm in 2039 Consecutive Cases.
AB  - BACKGROUND: Sterile ready-to-use acellular dermal matrix, introduced as an
      alternative to aseptic freeze-dried acellular dermal matrix for implant-based
      breast reconstruction, has been investigated in a limited number of studies. This
      study compared outcomes in implant-based breast reconstruction with ready-to-use
      and freeze-dried acellular dermal matrix. METHODS: The authors analyzed patients
      undergoing implant-based breast reconstruction with either freeze-dried or ready
      to-use acellular dermal matrix, including demographics, clinical variables, and
      outcomes. An a priori power analysis was performed and logistic regression
      modeling was used to quantify the effect of acellular dermal matrix on outcomes
      while controlling for potential confounders. RESULTS: A total of 1285 consecutive
      patients undergoing 2039 immediate prosthetic breast reconstructions constituted
      the population: 612 (n = 910 breasts) with freeze-dried matrix and 673 (n = 1129
      breasts) with ready-to-use acellular dermal matrix. The freeze-dried matrix
      cohort had a significantly higher rate of explantation compared with the ready-to
      use matrix cohort (18.0 percent versus 12.0 percent; p = 0.0036), but surgical
      site infection, wound dehiscence, mastectomy flap necrosis, seroma, and hematoma
      did not differ significantly between groups. On multivariate regression, patients
      undergoing reconstruction with freeze-dried matrix, compared to ready-to-use
      matrix, did not have higher odds of experiencing surgical-site infections (OR,
      1.064; p = 0.7455), but did have higher odds of explantation (OR, 1.570; p =
      0.0161). Tobacco use (OR, 2.809; p = 0.0002) and body mass index (OR, 1.054; p <
      0.0001) were also independent predictors of explantation. CONCLUSION: Immediate
      implant-based breast reconstruction with sterile ready-to-use acellular dermal
      matrix has a comparable overall safety profile and a lower rate of prosthetic
      explantations compared with aseptic freeze-dried acellular dermal matrix.
      CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

PMID- 30204679
TI  - The Relationship between Bone Remodeling and the Clockwise Rotation of the Facial
      Skeleton: A Computed Tomographic Imaging-Based Evaluation.
AB  - BACKGROUND: Information on the onset and gender differences of midfacial skeletal
      changes, including the complete understanding of the theory behind the clockwise
      rotational theory, remains elusive. METHODS: One hundred fifty-seven Caucasian
      individuals (10 men and 10 women aged 20 to 29 years, 30 to 39 years, 40 to 49
      years, 50 to 59 years, 60 to 69 years, 70 to 79 years, and 80 to 89 years, and
      eight men and nine women aged 90 to 98 years) were investigated. Multiplanar
      computed tomographic scans with standardized angle and distance measurements in
      all three anatomical axes and in alignment to the sella-nasion (horizontal) line
      were conducted. RESULTS: Both men and women displayed an increase in orbital
      floor angle (p < 0.001, maximum at 60 to 69 years), decrease in maxillary angle
      (p = 0.035, 40 to 49 years), increase in palate angle (p < 0.001, 50 to 59
      years), increase in vomer angle (p = 0.022, 30 to 39 years), but a decrease in
      the pterygoid angle (p = 0.002, 80 to 89 years). Orbital width decreased (p <
      0.001, 60 to 69 years), pyriform aperture width increased (p = 0.015, 60 to 69
      years), and midfacial height decreased with aging (p < 0.001, 60 to 69 years).
      CONCLUSIONS: Age-related changes of the midfacial skeleton occurred independently
      of gender, but at various time points in different locations. The observed
      changes seem to be driven by a bone resorption center located in the posterior
      maxilla, rather than by a rotational movement of the facial skeleton.

PMID- 30204680
TI  - The Stacked Hemiabdominal Extended Perforator Flap for Autologous Breast
      Reconstruction.
AB  - BACKGROUND: Options for bilateral autologous breast reconstruction in thin women
      are limited. The aim of this study was to introduce a novel approach to increase
      abdominal flap volume with the stacked hemiabdominal extended perforator (SHAEP)
      flap. The authors describe the surgical technique and analyze their results.
      METHODS: A retrospective study was conducted of all SHAEP flap breast
      reconstructions performed since February of 2014. Patient demographics, operative
      details, complications, and flap reexplorations were recorded. The bipedicled
      hemiabdominal flap was designed as a combination of the deep inferior epigastric
      artery perforator (DIEP) and a second, more lateral pedicle: the deep or
      superficial circumflex iliac perforator vessels, the superficial inferior
      epigastric artery, or a lumbar artery or intercostal perforator. RESULTS: A total
      of 90 SHAEP flap breast reconstructions were performed in 49 consecutive
      patients. Median operative time was 500 minutes (range, 405 to 797 minutes).
      Median hemiabdominal flap weight that was used for reconstruction was 598 g
      (range, 160 to 1389 g). No total flap losses were recorded. Recipient-site
      complications included partial flap loss (2.2 percent), hematoma (3.3 percent),
      fat necrosis (2.2 percent), and wound problems (4.4 percent). Minor donor-site
      complications occurred in five patients (10.2 percent). Most flaps were harvested
      on a combination of the DIEP and deep circumflex iliac artery vessels.
      CONCLUSIONS: This study demonstrated that the SHAEP flap is an excellent option
      for bilateral autologous breast reconstruction in women who require significant
      breast volume but have insufficient abdominal tissue for a bilateral DIEP flap.
      The bipedicled SHAEP flap allows for enhanced flap perfusion, increased volume,
      and abdominal contour improvement using a single abdominal donor site. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 30204681
TI  - The Constriction Arm Band Deformity in Brachioplasty Patients: Characterization
      and Incidence Using a Prospective Registry.
AB  - BACKGROUND: Demand for brachioplasty in the United States has seen a dramatic
      increase, from 338 procedures in 2000 to 17,860 in 2016. In this article, the
      authors present their series of arm band deformities not yet described in the
      literature. METHODS: This is a retrospective review of massive weight loss
      patients undergoing brachioplasty at their institution from 2000 to 2016.
      Preoperative and postoperative photographs were reviewed. Descriptive statistics
      and t test were used. RESULTS: One hundred seventy-two patients underwent
      brachioplasty, and 25 patients (15 percent) were identified with the deformity.
      Twenty-four (96 percent) were women, with an average age of 60 years (range, 36
      to 85 years) and a mean body mass index of 34 kg/m at the time of surgery
      (average, 2 years since gastric bypass; mean delta body mass index, 22 kg/m). The
      bands were generally single bands (100 percent) found bilaterally (68 percent) in
      the distal third (74 percent) of the upper arm and exacerbated (50 percent) by
      brachioplasty. The average specimen weighed 1005 g. The authors found that arm
      banding was associated with a higher current body mass index, but not with a
      maximum body mass index or delta body mass index. CONCLUSIONS: For massive weight
      loss patients, arm band deformity is a challenging problem that can be
      exacerbated by brachioplasty. It can be identified preoperatively to aid in
      counseling. The authors found patients with a higher current body mass index to
      be at a higher risk for the arm band deformity after brachioplasty. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Risk, IV.

PMID- 30204682
TI  - Development of the BODY-Q Chest Module Evaluating Outcomes following Chest
      Contouring Surgery.
AB  - BACKGROUND: Plastic surgery to improve chest appearance is becoming increasingly
      popular. The BODY-Q is a patient-reported outcome instrument designed for weight
      loss and/or body contouring. In this article, the authors describe the
      development of a new module for masculinizing chest contouring surgery. METHODS:
      Qualitative methods were used to develop the BODY-Q Chest Module, which was
      subsequently field-tested in Canada, the United States, The Netherlands, and
      Denmark between June of 2016 and June of 2017. Participants were aged 16 years or
      older and seen for gynecomastia, weight loss, or transman chest surgery. Data
      were collected using either a Web-based application or paper questionnaire. Rasch
      measurement theory analysis was performed. RESULTS: The sample included 739
      participants (i.e., 174 gynecomastia, 224 weight loss, and 341 gender-affirming).
      Rasch measurement theory analysis refined a 10-item chest scale and a five-item
      nipple scale. All items had ordered thresholds and good item fit, and scales
      evidenced reliability [i.e., person separation index and Cronbach alpha values
      were 0.95 and 0.98 (chest scale) and 0.87 and 0.94 (nipple scale), respectively].
      Scores for both scales correlated more strongly with similar (satisfaction with
      the body) versus dissimilar (psychological and social function) BODY-Q scales.
      The mean scores for the chest and nipple scales were significantly higher (p <
      0.001 on independent samples t tests) in participants who were postoperative
      compared with preoperative. CONCLUSION: This new BODY-Q Chest Module is a
      clinically meaningful and scientifically sound patient-reported outcome
      instrument that can be used to measure outcomes for masculinizing chest
      contouring surgery.

PMID- 30204683
TI  - Fat Grafting for Pedal Fat Pad Atrophy in a 2-Year, Prospective, Randomized,
      Crossover, Single-Center Clinical Trial.
AB  - BACKGROUND: By age 60, 30 percent of Americans suffer from fat pad atrophy of the
      foot. Forefoot fat pad atrophy results from long-term aggressive activity,
      genetically dictated foot type, multiple forefoot steroid injections, surgery,
      and foot trauma. METHODS: The authors present data from a 2-year, prospective,
      randomized crossover study performed to assess pain and disability indexes, fat
      pad thickness, forces, and pressures of stance and gait. Group 1 underwent fat
      grafting with 2 years of follow-up, and group 2 underwent conservative management
      for 1 year, then underwent fat grafting with 1 year of follow-up. RESULTS:
      Eighteen subjects (14 women and four men) constituted group 1. Thirteen subjects
      (nine women and four men) constituted group 2. Group 1 reported the worst pain at
      baseline and group 2 experienced the worst pain at 6- and 12-month standard-of
      care visits; pain for both groups improved immediately following fat grafting and
      lasted through study follow-up (p < 0.05). Group 1 demonstrated functional
      improvements at 12, 18, and 24 months postoperatively (p < 0.05), whereas group 2
      demonstrated the highest function at 12 months postoperatively (p < 0.05). Pedal
      fat pad thickness of subjects in group 1 increased postoperatively and returned
      to baseline thickness at 2 months postoperatively; subjects in group 2
      experienced return to baseline thickness at 6 months postoperatively (p < 0.01).
      Forces and pressures of stance and gait increased over the 2 years of follow-up
      for group 1 (p < 0.05). CONCLUSION: Pedal fat grafting provides long-lasting
      improvements in pain and function, and prevents against worsening from
      conservative management. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, I.

PMID- 30204684
TI  - Melanoma signature in Brazil: epidemiology, incidence, mortality, and trend
      lessons from a continental mixed population country in the past 15 years.
AB  - The current research aimed to understand melanoma epidemiology in Brazil and to
      evaluate temporal trends in incidence and mortality. The data came from Brazilian
      Hospital Cancer Registries, Population Based Cancer Registries, and the National
      Mortality Information System from 2000 to 2014. Descriptive statistics were used
      for epidemiological and clinical characteristics. To describe trends in change in
      incidence and mortality rates, the Average Annual Percentage Change (AAPC) was
      calculated. Between 2000 and 2013, in men, the median incidence rate rose from
      2.52 to 4.84, with an AAPC of +21.5% [95% confidence interval (CI): 15.4-28] and
      in women from 1.93 to 3.22 per 100 000, with an AAPC of +13.9% (95% CI: 8.1-20).
      Regarding mortality, between 2000 and 2014, the rates went from 0.85 to 0.9 per
      100 000 for men (AAPC=+0.8, 95% CI: 0.4-1.1) and from 0.56 for 0.53 per 100 000
      for women (AAPC=-0.1, 95% CI: -0.2 to 0). From the database, a total of 28 624
      patients with melanoma were included. Most of the patients were females (51.9%),
      White (75%) and with stage I or II (53.2%). Sex, ethnicity, education level,
      geographical area of the cancer center, topography, histology, time between
      diagnosis and treatment, and early death were significantly associated with
      distant metastases. Brazil is a large country with a very young population and a
      low rate of melanoma incidence and prevalence that should increase over the
      years. Understanding the trends attributed to melanoma is important for
      behavioral counseling interventions that focus on promoting skin cancer
      prevention.

PMID- 30204685
TI  - Mozart for Reducing Patient Anxiety During Colposcopy: A Randomized Controlled
      Trial.
AB  - OBJECTIVE: To test whether music by Mozart reduces anxiety among patients
      undergoing colposcopy. METHODS: In a randomized multicenter trial, we measured
      the reduction of the situation-specific anxiety of women hearing Mozart's
      Symphony No. 40 during colposcopy compared with women not hearing music using the
      State-Trait Anxiety Inventory. Secondary endpoints were reduction of heart rate
      (beats per minute), pain during and 10 minutes after colposcopy, general
      unpleasantness, anxiety during colposcopy, and overall satisfaction (11-item
      visual analog scales). Analysis was by intention to treat. A sample size of 104
      per group (N=208) was calculated to achieve 80% power to detect a difference of
      4.8 with a SD of 12.3 in anxiety scores. RESULTS: Between February 2017 and May
      2018, 212 women were randomized. The mean anxiety reduction was -9.4+/-10.8 SD in
      103 women in the music group and -9.0+/-10.6 in 102 women in the control group
      (P=.40). The secondary endpoints reduction of heart rate (-16.3+/-16.9 vs -15.4+/
      17.1; P=.37), pain during procedure (median 2 [interquartile range 1-4] vs 2 [1
      3.5]; P=.80), pain 10 minutes after examination (1 [0-1.75] vs 1 [0-2]; P=.42),
      general unpleasantness (3 [1-5.75] vs 4 [1-5.5]; P=.35), anxiety during
      examination (2 [1-5] vs 2 [1-6]; P=.28), and overall satisfaction (10 [9-10] vs
      10 [9-10]; P=.81) were also not different between the two study groups.
      CONCLUSION: Mozart's Symphony No. 40 does not reduce anxiety in women undergoing
      colposcopy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT03005795.

PMID- 30204686
TI  - Use of Kratom, an Opioid-like Traditional Herb, in Pregnancy.
AB  - BACKGROUND: Kratom (Mitragyna speciosa) is an herbal preparation with opioid-like
      effects made from a tree native to Southeast Asia and the Pacific Islands.
      Increasingly, kratom is used for self-treatment of opioid use disorder and
      recently has been associated with a multistate outbreak of salmonellosis. Few
      data are available on the clinical outcomes of kratom use in pregnancy. CASES: We
      present two cases of pregnant women presenting with kratom dependence. Both women
      presented with symptoms consistent with opioid withdrawal. Both women were
      initiated on opioid replacement, with successful treatment of symptoms.
      CONCLUSIONS: Kratom is an emerging self-treatment for opioid use disorder in the
      obstetric population. Obstetric care providers should be aware of kratom and
      consider opioid replacement for pregnant women with kratom dependence.

PMID- 30204688
TI  - Intrauterine Device Expulsion After Postpartum Placement: A Systematic Review and
      Meta-analysis.
AB  - OBJECTIVE: To estimate expulsion rates among women with postpartum intrauterine
      device (IUD) placement by timing of insertion, IUD type, and delivery method.
      DATA SOURCES: We searched PubMed, Cochrane Library, and ClinicalTrials.gov from
      1974 to May 2018. METHODS OF STUDY SELECTION: We searched databases for any
      published studies that examined postpartum placement of a copper IUD or
      levonorgestrel intrauterine system and reported counts of expulsions. We assessed
      study quality using the U.S. Preventive Services Task Force evidence grading
      system. We calculated pooled absolute rates of IUD expulsion and estimated
      adjusted relative risks (RRs) for timing of postpartum placement, delivery
      method, and IUD type using log-binomial multivariable regression model.
      TABULATION, INTEGRATION, AND RESULTS: We identified 48 level I to II-3 studies of
      poor to good quality. Pooled rates of expulsion varied by timing of IUD
      placement, ranging from 1.9% with interval placements (4 weeks postpartum or
      greater), 10.0% for immediate placements (10 minutes or less after placental
      delivery), and 29.7% for early placements (greater than 10 minutes to less than 4
      weeks postpartum). Immediate and early postpartum placements were associated with
      increased risk of expulsion compared with interval placement (adjusted RR 7.63,
      95% CI 4.31-13.51; adjusted RR 6.17, 95% CI 3.19-11.93, respectively). Postpartum
      placement less than 4 weeks after vaginal delivery was associated with an
      increased risk of expulsion compared with cesarean delivery (adjusted RR 5.19,
      95% CI 3.85-6.99). Analysis of expulsion rates at less than 4 weeks postpartum
      also indicated that the levonorgestrel intrauterine system was associated with a
      higher risk of expulsion (adjusted RR 1.91, 95% CI 1.50-2.43) compared with
      CuT380A. CONCLUSION: Postpartum IUD expulsion rates vary by timing of placement,
      delivery method, and IUD type. These results can aid in counseling women to make
      an informed choice about when to initiate their IUD and to help institutions
      implement postpartum contraception programs.

PMID- 30204687
TI  - Intrapartum Fetal Heart Rate Tracing Among Small-for-Gestational Age Compared
      With Appropriate-for-Gestational-Age Neonates.
AB  - OBJECTIVE: To compare fetal heart rate (FHR) patterns during the last hour of
      labor between small-for-gestational-age (SGA; birth weight less than the 10th
      percentile for gestational age) and appropriate-for-gestational-age (AGA; birth
      weight at the 10-90th percentile) neonates at 36 weeks of gestation or greater.
      We also compared the rate of cesarean delivery and composite neonatal morbidity
      among SGA and AGA newborns. METHODS: This is a secondary analysis of a randomized
      trial of intrapartum fetal electrocardiographic ST-segment analysis. We excluded
      women with chorioamnionitis, insufficient duration of FHR tracing in the hour
      before delivery, and anomalous newborns. Fetal heart rate patterns were
      categorized by computerized pattern recognition software (PeriCALM Patterns).
      Composite neonatal morbidity was defined as any of the following: intrapartum
      fetal death, Apgar score 3 or less at 5 minutes, cord artery pH 7.05 or less,
      base deficit 12 mmol/L or greater, neonatal seizure, intubation at delivery,
      neonatal encephalopathy, and neonatal death. Logistic regression was used to
      evaluate the association between FHR patterns and SGA adjusted for magnesium
      sulfate exposure and stage of labor. RESULTS: Of the 11,108 women randomized, 85%
      (n=9,402) met inclusion criteria, of whom 9% were SGA. In the last hour, the
      likelihood of accelerations was significantly lower among SGA than AGA neonates
      (72.4% vs 66.8%; P=.001). Variable decelerations lasting greater than 60 seconds,
      with depth greater than 60 beats per minute (bpm) or nadir less than 60 bpm, were
      significantly more common with SGA than AGA (all P<.001). The rate of late
      decelerations, prolonged decelerations, or bradycardia were similar between SGA
      and AGA (all P>.05). Cesarean delivery for fetal indications was significantly
      more common with SGA (7.0%) than AGA (4.0%; P<.001). The composite neonatal
      morbidity was 1.4% among SGA and 1.0% among AGA (odds ratio 1.40, 95% CI 0.74
      2.64). CONCLUSION: Although the FHR patterns in the last hour of labor differ
      among SGA and AGA neonates, as does the rate of cesarean delivery, the composite
      neonatal morbidity was similar.

PMID- 30204689
TI  - Cervical Pessary Compared With Vaginal Progesterone for Preventing Early Preterm
      Birth: A Randomized Controlled Trial.
AB  - OBJECTIVE: To compare the effectiveness of a cervical pessary and vaginal
      progesterone to prevent spontaneous preterm births in pregnant women with
      cervical lengths 25 mm or less as measured by transvaginal ultrasonography.
      METHODS: This was a multicenter, open-label, randomized, noninferiority trial.
      Women with singleton pregnancies and a short cervix (25 mm or less) measured
      transvaginally at the second-trimester ultrasonogram were invited to participate.
      They were computer-randomized (one to one) into cervical pessary placement or
      treatment with vaginal progesterone (200 mg/24 hours). The primary outcome was
      spontaneous preterm delivery before 34 weeks of gestation. The noninferiority
      margin was set at 4% with a 0.025 one-sided alpha level and a statistical power
      of 80%. That is, if the 95% CI upper bound exceeded 4%, the pessary could not be
      deemed noninferior. A sample size of 254 women was required to show
      noninferiority of the pessary to progesterone. RESULTS: The trial was conducted
      from August 2012 to April 2016 with the participation of 27 Spanish hospitals. A
      total of 254 patients were enrolled and 246 included in the intention-to-treat
      analysis. Demographic and baseline characteristics were similar across groups.
      The rate of spontaneous delivery before 34 weeks of gestation was 14% (n=18/127)
      in the pessary group and 14% (n=17/119) in the progesterone group with a risk
      difference of -0.11% (95% CI -8.85% to 8.62%; P=.99), that is, noninferiority was
      not shown for the pessary. The incidence of increased vaginal discharge (87% vs
      71%, P=.002) and discomfort (27% vs 3%, P<.001) was significantly higher in the
      pessary group. CONCLUSION: A cervical pessary was not noninferior to vaginal
      progesterone for preventing spontaneous birth before 34 weeks of gestation in
      pregnant women with short cervixes. CLINICAL TRIAL REGISTRATION: EU Clinical
      Trials Register, 2012-000241-13; ClinicalTrials.gov, NCT01643980.

PMID- 30204690
TI  - Beyond Silence and Inaction: Changing the Response to Experiences of Racism in
      the Health Care Workforce.
AB  - The issue of race and ethnicity within obstetrics and gynecology has come to the
      forefront in the current social and political climate. Understanding the ill
      effects of racism within the clinical space requires an acknowledgment of both
      the ongoing problem and current limitations in the state of knowledge and praxis
      among clinicians, trainees, and educators alike. In this commentary, the issue of
      race and racism within obstetrics and gynecology is discussed through a case of
      discrimination experienced by an intern working in an urban, academic hospital.
      By attending to the different layers of hierarchy within medical education and
      care as well as the multitude of silences from potential allies, we demonstrate a
      critical need to understand racism and inequality in the clinical and educational
      space. We deconstruct the issue of race and racism by contextualizing it with
      ongoing discussions in the social sciences and public health as well as wider
      discussions of the relationship of race with professional training and employment
      in biomedical fields. Finally, we offer both action items and calls for future
      educational and practice-based solutions to affect change in the way obstetrics
      and gynecology is taught and practiced.

PMID- 30204692
TI  - Institutional Responses to Harassment and Discrimination in Obstetrics and
      Gynecology.
AB  - Institutional harassment and discrimination are prevalent in the field of
      medicine and are detrimental to the well-being of individuals, teams, and the
      work environment. The familiar framework of an obstetric safety bundle is used
      here to propose 11 practical steps a health care team or institution may take to
      prepare for and respond to workplace harassment and discrimination in a
      systematic fashion.

PMID- 30204691
TI  - Patient and Health Care Provider Factors Associated With Prescription of Opioids
      After Delivery.
AB  - OBJECTIVE: To identify patient and health care provider characteristics
      associated with receipt of a high amount of prescribed opioids at postpartum
      discharge. METHODS: This was a retrospective case-control study of all opioid
      naive women delivering at a single, high-volume tertiary care center between
      December 1, 2015, and November 30, 2016. Inpatient, outpatient, pharmacy, and
      billing records were queried for clinical, prescription, and health care provider
      (training, age, gender) data. The discharging health care provider, whether an
      opioid prescription was provided, and the details of any opioid prescription were
      determined. A high amount of prescribed opioids was defined as morphine milligram
      equivalents greater than the 90th percentile (determined as 300 morphine
      milligram equivalents for vaginal and 500 morphine milligram equivalents for
      cesarean delivery). Multivariable logistic regression models with random effects
      were used to identify patient and health care provider factors independently
      associated with receipt of a high amount of prescribed opioids at discharge.
      Findings were analyzed separately by mode of delivery. RESULTS: The analysis
      included 12,362 women. High amounts of opioids were prescribed for 636 of 9,038
      (7.0%) women who delivered vaginally and 241 of 3,288 (7.3%) of those delivering
      by cesarean. In multivariable analysis, patient factors associated with receipt
      of a high amount of prescribed opioids at discharge after a vaginal delivery
      included nulliparity, intrapartum neuraxial anesthesia, major laceration, and
      infectious complication. Discharge by a trainee physician was associated with
      decreased odds of receiving a high amount of opioids (8.5% vs 1.9%; adjusted odds
      ratio [OR] 0.08, 95% CI 0.01-0.53). For women who underwent cesarean delivery,
      the only patient factor associated with receipt of a high amount of prescribed
      opioids was hemorrhage. Discharge by a trainee physician was associated with
      decreased odds of being provided a high-amount opioid prescription (7.9% vs 0.4%;
      adjusted OR 0.01, 95% CI 0.00-0.36). CONCLUSION: Even after adjusting for patient
      factors, discharge by a trainee physician is significantly associated with
      decreased odds of a high amount of prescribed opioids at postpartum discharge.

PMID- 30204693
TI  - Bias in Obstetrician-Gynecologists' Workplaces.
AB  - Obstetrician-gynecologists (ob-gyns) face similar types of biases in the
      workplace as any people in society. In this first of three articles exploring
      this issue, we present the stories from ob-gyns who describe their experiences
      dealing with these biases. These stories serve to personalize the issue and to
      encourage us to personally face bias in the workplace to build our own resilience
      and strength, to support those who are personally attacked or diminished, and to
      develop workplace cultures that are inclusive, diverse, and strong.

PMID- 30204695
TI  - Gynecologic Health and Disease Research at the Eunice Kennedy Shriver National
      Institute of Child Health and Human Development: A Scientific Vision.
AB  - In May 2016, the newly formed Gynecologic Health and Disease Branch in the Eunice
      Kennedy Shriver National Institute of Child Health and Human Development invited
      experts to a 2-day meeting aimed at identification of emerging opportunities in
      gynecologic investigation. Four primary disorders were chosen for emphasis
      because they represent the majority of the current Gynecologic Health and Disease
      Branch portfolio: uterine leiomyomas, endometriosis, pelvic floor disorders, and
      gynecologic pain conditions. Discussions generated a set of seven cross-cutting
      themes, which encompass both gaps in our current knowledge and potential
      directions for further research. These themes formed a continuum for
      understanding these disorders beginning with the need for classification systems,
      improved understanding of the natural history and etiology of these disorders,
      development of novel diagnostics, identification of opportunities for prevention,
      and the generation of new treatments using cutting-edge approaches. Along with
      these themes, three broad strategies were proposed to facilitate future research.
      First, investigators should improve utilization of existing research resources
      and focus on developing new resources to include databases, biospecimen
      repositories, animal models, and patient cohorts. Second, multidisciplinary
      scientific partnerships should be strengthened to bring new insights and
      approaches to gynecologic research. Third, patient and health care provider
      education must be promoted to ensure timely and accurate diagnosis and optimize
      treatment of gynecologic disorders. This article provides a summary of the
      workshop themes and suggestions, several of which have already been implemented
      through the development of program priorities and funding opportunity
      announcements aimed at improving women's reproductive health.

PMID- 30204696
TI  - Eliminating Preventable Maternal Deaths in the United States: Progress Made and
      Next Steps.
AB  - The crisis of a rising maternal mortality ratio in the United States continues to
      receive attention in both the scientific literature and the lay press. To
      continue to make progress in preventing these deaths, we must celebrate our
      successes and clearly delineate the next steps. The Centers for Disease Control
      and Prevention program, Building U.S. Capacity to Review and Prevent Maternal
      Deaths, recently published a report from nine maternal mortality review
      committees, which accomplishes just that. The report is a collaborative effort
      from maternal mortality review committees demonstrating the capacity to do three
      important tasks: 1) collect data in a standardized fashion across maternal
      mortality review committees throughout the United States, 2) assess
      preventability of maternal deaths by consensus from experts on multidisciplinary
      state committees, and 3) create recommendations based on maternal death review
      with far-reaching effect. Next steps involve expansion of this standardized
      process to maternal mortality review committees in every state and translation of
      those recommendations into state-specific action through the use of local
      resources such as state perinatal quality care collaboratives. This commentary
      summarizes the content of the report from nine maternal mortality review
      committees.

PMID- 30204694
TI  - Trends and Outcomes Associated With Using Long-Acting Opioids During Delivery
      Hospitalizations.
AB  - OBJECTIVE: To assess trends in use of long-acting opioids during delivery
      hospitalizations. METHODS: The Perspective database, an administrative inpatient
      database that includes medication receipt, was analyzed to evaluate patterns of
      long-acting opioid use during delivery hospitalizations from January 2006 through
      March 2015. Medications evaluated included methadone, formulations including
      buprenorphine and extended-release formulations of oxycodone, morphine, fentanyl,
      and other opioids. Temporal trends in use of these medications were determined.
      Unadjusted and adjusted models evaluating the role of demographic and hospital
      factors were created evaluating both use of these medications and risk for severe
      morbidity. Risk for severe morbidity was determined based on Centers for Disease
      Control and Prevention criteria. RESULTS: Our analysis included 2,994,630
      delivery hospitalizations meeting study criteria. Over the entire study period,
      use of long-acting opioids increased significantly from 457 to 844 per 100,000
      deliveries. Although buprenorphine and methadone use increased, use of other long
      acting opioids decreased. In 2006, methadone and buprenorphine accounted for less
      than one third of all long-acting opioids used during delivery hospitalizations.
      By 2015, buprenorphine and methadone represented 73.5% of long-acting opioids
      used. In adjusted and unadjusted models, risk for severe morbidity was
      significantly lower with buprenorphine or methadone compared with other long
      acting opioids. Restricting the cohort to only women with drug abuse or
      dependence, risk for severe morbidity was lower with methadone and buprenorphine
      than without any long-acting opioids. CONCLUSION: Increased use of methadone and
      buprenorphine in this study supports the feasibility of use of these medications
      during pregnancy and uptake of clinical recommendations for women with opioid use
      disorder. Use of methadone and buprenorphine is associated with decreased
      maternal morbidity, although causation cannot be presumed from this study model.

PMID- 30204697
TI  - Choice of Prophylactic Antibiotics and Surgical Site Infections After Cesarean
      Delivery.
AB  - OBJECTIVE: To examine the rate of surgical site infection according to the choice
      of antibiotics in women undergoing cesarean delivery. METHODS: We conducted a
      retrospective cohort study of women undergoing cesarean delivery (labored,
      unlabored, and scheduled) from 2012 to 2017. Women with chorioamnionitis and
      those who did not receive any antibiotics were excluded. Our primary outcome was
      defined a priori as a composite of cellulitis, endometritis, deep wound
      infection, abdominopelvic abscess, and sepsis. Outcomes were examined according
      to the choice of antibiotics: cefazolin, a standard alternative (both clindamycin
      and gentamicin), and inappropriate alternatives (such as clindamycin only). A
      multivariable logistic regression model was used to calculate the propensity
      score for each observation, which was the probability of receiving a particular
      antibiotic regimen. The propensity score-adjusted logistic regression models were
      conducted to calculate adjusted odds ratios (ORs) and 95% CIs. Firth's penalized
      likelihood approach was applied to address issues of rare events. RESULTS: Among
      6,584 selected women, 6,163 (93.6%), 274 (4.2%), and 147 (2.2%) received
      cefazolin, a standard alternative, and inappropriate alternatives, respectively.
      Use of standard alternative antibiotics compared with cefazolin was not
      associated with increased odds of the primary outcome (crude OR 1.50 [0.92-2.46];
      adjusted OR 1.63 [0.97-2.60]) but was associated with increased odds of
      cellulitis (crude OR 2.07 [1.16-3.70]; adjusted OR 1.93 [1.03-3.31]). Use of
      inappropriate alternative antibiotics compared with cefazolin was associated with
      increased odds of the primary outcome (crude OR 4.37 [2.80-6.83]; adjusted OR
      4.13 [2.59-6.36]) as well as some components of the composite outcome such as
      endometritis before discharge (crude OR 6.85 [3.94-11.90]; adjusted OR 6.68 [3.69
      11.44]) and cellulitis (crude OR 3.36 [1.78-6.34]; adjusted OR 3.23 [1.63-5.81]).
      CONCLUSION: Both standard alternative and inappropriate alternatives were
      associated with increased odds of surgical site infections compared with
      cefazolin.

PMID- 30204698
TI  - Maternal Outcomes Associated With Lower Range Stage 1 Hypertension.
AB  - OBJECTIVE: To evaluate maternal and neonatal outcomes in healthy, nulliparous
      women classified with stage 1 hypertension under the revised American College of
      Cardiology and American Heart Association Guidelines and to evaluate the effects
      of low-dose aspirin on maternal and neonatal outcomes in this population.
      METHODS: We conducted a secondary analysis of data from a multicenter randomized,
      double-blind, placebo-controlled trial of low-dose aspirin for prevention of
      preeclampsia in nulliparous, low-risk women recruited between 13 and 25 weeks of
      gestation. Of the 3,134 nulliparous women enrolled in the original study, 2,947
      women with singleton pregnancies and without missing data were included in this
      analysis. Blood pressure was measured at enrollment between 13 and 25 weeks of
      gestation and outcomes were adjudicated from the medical record. RESULTS: One
      hundred sixty-four participants were identified with lower range stage 1
      hypertension (5.6%), systolic blood pressure 130-135 mm Hg, diastolic blood
      pressure 80-85 mm Hg, or both by the new American College of Cardiology-American
      Heart Association guidelines. Within the placebo group (n=1,482), women with
      stage 1 hypertension had a significantly increased incidence of preeclampsia
      compared with normotensive women, 15.3% (15/98) vs 5.4% (75/1,384) (relative risk
      2.66, 95% CI 1.56-4.54, P<.001). Moreover, women with stage 1 hypertension had an
      increased incidence of gestational diabetes mellitus (6.1% vs 2.5%, P=.03) and
      more indicated preterm deliveries (4.2% vs 1.1%, P=.01). Comparing women with
      stage 1 hypertension and normotensive women receiving low-dose aspirin during
      pregnancy (n=1,465), no differences in rates of preeclampsia (7.6% vs 4.4%,
      respectively, P=.2), gestational diabetes mellitus, or indicated preterm
      deliveries were observed. Rates of placenta abruption, small for gestational age,
      and spontaneous preterm birth did not differ significantly between groups.
      CONCLUSION: Application of the new American College of Cardiology-American Heart
      Association guidelines in a pregnant population identifies a cohort of women who
      are at increased risk for preeclampsia, gestational diabetes mellitus, and
      preterm birth.

PMID- 30204699
TI  - Delayed Childbearing as a Growing, Previously Unrecognized Contributor to the
      National Plural Birth Excess.
AB  - OBJECTIVE: To establish the annual and cumulative multiyear contribution of
      delayed childbearing to the national plural birth excess. METHODS: Using publicly
      available national birth data reported by the National Center for Health
      Statistics, we estimated the contribution of delayed childbearing to the national
      plural birth excess through 2016. To this end, the observed as well as the
      maternal age- and race-adjusted national plural birth rates were assessed before
      (1949-1966; n=71,570,717) and during (1971-2016; n=166,817,655) the assisted
      reproduction era. Comparable estimates through 2025 relied on simulated
      projections. RESULTS: The relative risk estimates of unassisted plural births by
      maternal age before the assisted reproduction era (1949-1966) proved unimodal and
      race-dependent. The risk of unassisted plural births in 35- to 39-year-old black
      women proved 2.75-fold higher than that of 15- to 19-year-old counterparts
      (39.81/1,000 to 14.48/1,000; 95% CI 2.67-2.83). A 2.47-fold risk increment was
      noted for comparably aged white women (28.76/1,000 to 11.63/1,000; 95% CI 2.43
      2.52). Similar age-dependent risk increments were obtained for twin and higher
      order births. An increasingly prominent delayed childbearing trend during the
      assisted reproduction era (1971-2016) gave rise to 255,964 (95% CI 134,746
      375,581) and 66,271 (95% CI 34,099-96,197) unassisted plural births by white and
      black women, respectively. In 2016 alone, delayed childbearing accounted for 24%
      (95% CI 15-32%) and 38% (95% CI 28-47%) of the national plural birth excess for
      white and black women, respectively. By 2025, delayed childbearing could account
      for as much as 46% (95% CI 32-60%) and 40% (95% CI 30-53%) of the national plural
      birth excess for white and black women, respectively. CONCLUSION: Delayed
      childbearing, a growing contributor to the national plural birth excess
      previously solely ascribed to assisted reproduction, warrants greater
      consideration in future clinical, analytic, and policy deliberations as well as
      in individual family planning decisions.

PMID- 30204700
TI  - Vaginal Cuff Dehiscence and Evisceration: A Review.
AB  - Vaginal cuff dehiscence is an infrequent complication of hysterectomy, with the
      potential for evisceration and additional morbidity. This review aims to describe
      the incidence, risk factors, preventative measures, and management.
      Identification of specific risk factors is problematic because many studies
      either lack comparison groups or are underpowered as a result of the rarity of
      this complication. Good surgical technique to optimize vaginal cuff healing and
      minimize the risk of postoperative cuff infection are important as is avoidance
      of early intercourse, traumatic vaginal penetration, or excess strain on the
      vaginal cuff during the postoperative period. Judicious use of electrocautery or
      other thermal energy, use of delayed absorbable sutures, and adequate tissue
      bites can further decrease the risk of dehiscence. Prompt recognition and
      management are critical to achieve best outcomes.

PMID- 30204703
TI  - Pregnancy and Naltrexone Pharmacotherapy.
AB  - A 25-year-old woman, gravida 3 para 2 at 12 weeks of gestation, with two prior
      cesarean deliveries, presents for prenatal care. She is in treatment for opioid
      use disorder on extended-release naltrexone injection, with a history of opioid
      overdose, relapse, and poor treatment adherence on methadone and buprenorphine.
      She asks, "Is it safe for my baby if I continue on this medication? How will you
      manage my postoperative pain?"

PMID- 30204702
TI  - Delivery-to-Delivery Weight Gain and Risk of Hypertensive Disorders in a
      Subsequent Pregnancy.
AB  - OBJECTIVE: To estimate whether weight gain between deliveries is associated with
      an increased risk of hypertensive disorders in a subsequent pregnancy. METHODS:
      This is a case-control study of women who had two live singleton births of at
      least 24 weeks of gestation at a single maternity hospital from January 1, 2005,
      to December 31, 2015, with no hypertensive disorder documented in the index
      pregnancy. Maternal weight gain between deliveries was measured as the change in
      body mass index (BMI) at delivery. Women who were diagnosed with any hypertensive
      disorder in the subsequent pregnancy were compared with those who experienced no
      hypertensive disorder in the subsequent pregnancy using chi statistics for
      categorical variables and t tests for continuous variables. Logistic regression
      was used to determine whether weight gain remained independently associated with
      hypertensive disorders after adjusting for potential confounders. RESULTS: Of
      1,033 women, 188 (18.2%) were diagnosed with a hypertensive disorder in the
      subsequent pregnancy. Of these, 166 (88.3%) had a hypertensive disorder specific
      to pregnancy (gestational hypertension; preeclampsia; superimposed preeclampsia;
      or hemolysis, elevated liver enzymes, and low platelet count syndrome), and 22
      (11.7%) had chronic hypertension only. Greater weight gain between deliveries was
      significantly associated with a higher frequency of hypertensive disorders, which
      remained significant for a BMI increase of at least 2 kg/m in multivariable
      analyses (adjusted odds ratio [OR] 1.76, 95% CI 1.14-2.74 for 2 to less than 4
      kg/m, adjusted OR 3.19, 95% CI 1.86-5.47 for 4 kg/m or more). Conversely, weight
      loss of 2 kg/m or more was associated with a decreased risk of a hypertensive
      disorder (adjusted OR 0.41, 95% CI 0.21-0.81). CONCLUSION: Among women with no
      hypertensive disorder noted in an index pregnancy, an increase in BMI of at least
      2 kg/m between deliveries was independently associated with an increased risk of
      a hypertensive disorder in a subsequent pregnancy.

PMID- 30204701
TI  - Association Between Gestational Weight Gain and Perinatal Outcomes.
AB  - OBJECTIVE: To evaluate the association between gestational weight gain and
      maternal and neonatal outcomes in a large, geographically diverse cohort.
      METHODS: Trained chart abstractors at 25 hospitals obtained maternal and neonatal
      data for all deliveries on randomly selected days over 3 years (2008-2011).
      Gestational weight gain was derived using weight at delivery minus prepregnancy
      or first-trimester weight and categorized as below, within, or above the
      Institute of Medicine (IOM) guidelines in this retrospective cohort study.
      Maternal (primary or repeat cesarean delivery, third- or fourth-degree
      lacerations, severe postpartum hemorrhage, hypertensive disease of pregnancy) and
      neonatal (preterm birth, shoulder dystocia, macrosomia, hypoglycemia) outcomes
      were compared among women in the gestational weight gain categories in unadjusted
      and adjusted analyses with odds ratios (ORs) and 95% CI reported. Covariates
      included age, race-ethnicity, tobacco use, insurance type, parity, prior cesarean
      delivery, pregestational diabetes, hypertension, and hospital type. RESULTS: Of
      the 29,861 women included, 51% and 21% had gestational weight gain above and
      below the guidelines, respectively. There was an association between gestational
      weight gain above the IOM guidelines and cesarean delivery in both nulliparous
      women (adjusted OR 1.44, 95% CI 1.31-1.59) and multiparous women (adjusted OR
      1.26, 95% CI 1.13-1.41) and hypertensive diseases of pregnancy in nulliparous and
      multiparous women combined (adjusted OR 1.84, 95% CI 1.66-2.04). For the neonatal
      outcomes, gestational weight gain above the IOM guidelines was associated with
      shoulder dystocia (adjusted OR 1.74, 95% CI 1.41-2.14), macrosomia (adjusted OR
      2.66, 95% CI 2.03-3.48), and neonatal hypoglycemia (adjusted OR 1.60, 95% CI 1.16
      2.22). Gestational weight gain below the guidelines was associated with
      spontaneous (adjusted OR 1.50, 95% CI 1.31-1.73) and indicated (adjusted OR 1.34,
      95% CI 1.12-1.60) preterm birth. CONCLUSION: In a large, diverse cohort with
      prospectively collected data, gestational weight gain below or above guidelines
      is associated with a variety of adverse pregnancy outcomes.

PMID- 30204705
TI  - Acute Respiratory Distress Syndrome After Uterine Artery Embolization.
AB  - INTRODUCTION: Although uterine artery embolization has been established as a less
      invasive alternative to hysterectomy or myomectomy for the treatment of uterine
      leiomyomas, it is not devoid of life-threatening complications. CASE: We present
      the case of a 44-year-old patient who developed a severe systemic inflammatory
      response and acute respiratory distress syndrome 5 weeks after uterine artery
      embolization of a large multileiomyomatous uterus. Deterioration of her clinical
      status prompted an emergency hysterectomy that led to rapid improvement.
      CONCLUSION: Although fatalities from septicemia after uterine artery embolization
      have been reported, aseptic inflammatory responses to uterine degeneration can
      also lead to multiorgan failure. With recent studies refuting uterine size and
      leiomyoma location as risk factors, further research is needed to help select
      appropriate uterine artery embolization candidates.

PMID- 30204704
TI  - Prenatal Treatment and Outcomes of Women With Opioid Use Disorder.
AB  - OBJECTIVE: To describe the characteristics, treatment, and outcomes of pregnant
      women with opioid use disorder. METHODS: Women attending an obstetric and
      addiction recovery clinic in Boston from 2015 to 2016 were enrolled in a
      prospective cohort study and followed through delivery (N=113). Buprenorphine or
      methadone was initiated clinically. The Addiction Severity Index was administered
      at enrollment. Prenatal and delivery data were systematically abstracted from
      medical charts. RESULTS: Most women in the cohort were non-Hispanic white (80.5%)
      with a mean age of 28 years. Few women were married (8.9%). More than half of the
      cohort had been incarcerated, 29.2% had current legal involvement, and 15.0%
      generally had unstable housing. A majority (70.8%) were infected with hepatitis C
      and histories of sexual (56.6%) and physical (65.5%) abuse were prevalent.
      Regular substance used included heroin (92.0%), injection heroin (83.2%), other
      opioids (69.0%), marijuana (73.5%), alcohol (56.6%), and cocaine (62.8%). Fifty
      nine women (52.2%) were treated initially with prenatal buprenorphine and 54
      (47.8%) with methadone; 49.6% also were taking concomitant psychotropic
      medications. Employment (0.766+/-0.289) and psychologic (0.375+/-0.187) Addiction
      Severity Index scores were the highest, indicating the most severe problems in
      these areas. Opioid use relapse did not differ by treatment (44.7% overall).
      Thirteen (22.5%) of 59 women treated with buprenorphine transitioned to methadone
      mainly because of positive opioid screens. Overall, 23.0% (n=26) of the cohort
      discontinued clinical care. The number of pregnancy losses was small (three
      therapeutic abortions, four miscarriages, one stillbirth), with an overall live
      birth rate of 90.8% (95% CI 82.7-95.9). CONCLUSION: These data on the social
      circumstances, substance use, treatment, and treatment outcomes of pregnant women
      with opioid use disorder may help clinicians to understand and treat this
      clinically complex population.

PMID- 30204707
TI  - Experiences of newly diagnosed cancer patients in confronting the finitudes of
      life: a qualitative systematic review protocol.
AB  - REVIEW QUESTION: The question of this review is: what is the experience of newly
      diagnosed patients with cancer when facing the finitude of life and undergoing
      initial anti-cancer treatment?

PMID- 30204706
TI  - Experiences of learning, development and preparedness for clinical practice among
      undergraduate paramedicine students, graduate/intern paramedics and their
      preceptors: a systematic review protocol.
AB  - REVIEW QUESTION: The question of this review is: what are the barriers and
      facilitators related to learning, development, and preparedness for practice from
      the perspective of undergraduate paramedicine students, graduate/intern
      paramedics and the preceptors/trainers that facilitate learning?

PMID- 30204708
TI  - Experiences of women who have planned unassisted home births: a systematic review
      protocol.
AB  - REVIEW QUESTION/OBJECTIVE: The objective of this review is to identify, appraise
      and synthesize the qualitative evidence on the experiences of women in high
      resource countries who have planned unassisted home births. This qualitative
      review aims to answer the following question: what are the experiences of women
      who have planned unassisted home births?

PMID- 30204710
TI  - Effectiveness of nurse-led cardiac rehabilitation programs following coronary
      artery bypass graft surgery: a systematic review.
AB  - REVIEW OBJECTIVE: The objective of this review was to investigate the
      effectiveness of nurse-led cardiac rehabilitation programs following coronary
      artery bypass graft surgery on patients' health-related quality of life and
      hospital readmission. INTRODUCTION: Coronary heart disease is a major cause of
      death and disability worldwide, putting a great strain on healthcare resources.
      For the past two decades, population-wide primary prevention and individual
      healthcare approaches have resulted in a dramatic decline in overall cardiac
      mortality. Over the intervening years, surgical techniques in cardiology have
      also improved substantially. As a result, long-term outcomes in patients treated
      with coronary artery bypass graft surgery have established the treatment's
      effectiveness and survival benefit. Furthermore, participating in cardiac
      rehabilitation following coronary artery bypass graft surgery has also
      demonstrated a significant decrease in all-cause cardiac mortality in these
      patients. INCLUSION CRITERIA: This review included studies with participants aged
      18 years and over, post coronary artery bypass graft surgery that evaluated nurse
      led cardiac rehabilitation (CR) programs compared with usual care or other forms
      of CR. The outcomes of interest were the health-related quality of life and
      hospital readmissions following coronary artery bypass graft surgery and measured
      using validated scales. Randomized controlled trials reported in English- between
      2000 to June 2017 were considered for inclusion. METHODS: The search strategy
      aimed to find both published and unpublished studies using a three-step search
      strategy. An initial search of MEDLINE, CINAHL and Scopus was undertaken,
      followed by a search for unpublished studies including Dissertation Abstracts
      International, ProQuest Dissertations and Theses, Google Scholar, MedNar and
      ClinicalTrials.gov. Papers selected for retrieval were assessed by two
      independent reviewers for methodological validity prior to inclusion in the
      review using the standardized critical appraisal tools from the Joanna Briggs
      Institute System for the Unified Management, Assessment and Review of Information
      (JBI SUMARI). Quantitative data was extracted from papers included in the review
      using the standardized data extraction tool from JBI-SUMARI. No meta-analysis was
      undertaken due to heterogeneity of the outcome measures. All results were subject
      to double data entry. Effect sizes expressed as risk ratio (for categorical data)
      and weighted mean differences (for continuous data) and their 95% confidence
      intervals were calculated for analysis. RESULTS: Three trials involving 329
      patients were included in the final review. The trials that investigated the
      effect of home based cardiac rehabilitation programs compared to usual care at
      six weeks, three months and six months follow-up demonstrated no statistically
      significant difference in health-related quality of life at any of the follow-up
      periods. However, one study demonstrated significantly higher scores related to
      health-related quality of life among those who received nurse-led home based
      cardiac rehabilitation (154.93 +/- 4.6) compared to those who received usual care
      (134.20 +/- 8.2) at two months follow-up. No trials were identified that compared
      the effectiveness of nurse-led cardiac rehabilitation programs following coronary
      artery bypass graft surgery on readmissions to hospital. CONCLUSION: There is not
      enough evidence to support or discourage nurse-led cardiac rehabilitation
      programs on health-related quality of life in patients following coronary artery
      bypass graft surgery. However, the sparse data available suggests improvements in
      health-related quality of life at two months follow-up among those who received a
      nurse-led program. Further large-scale multicenter trials with standardized
      methodology are needed to determine the effect of nurse-led cardiac
      rehabilitation programs on health-related quality of life and rates of
      readmission to hospital following coronary artery bypass graft surgery.

PMID- 30204709
TI  - Dietary management in people with an ileostomy: a scoping review protocol.
AB  - REVIEW QUESTION/OBJECTIVE: The objective of this scoping review is to identify
      and map the evidence for oral dietary management of ileostomies.The primary
      review question is: what oral dietary strategies for managing ileostomies in
      humans have been reported?Secondary review questions are: i) what types of
      evidence have considered oral dietary strategies for managing ileostomies; ii)
      what aspects of ileostomy management, for example, stoma output or flatulence,
      are the oral dietary strategies considered to affect; and iii) what sources do
      people with an ileostomy receive dietary advice from?

PMID- 30204711
TI  - Effectiveness of phosphate binders in adult patients with end stage renal disease
      receiving hemodialysis: a systematic review.
AB  - OBJECTIVES: The objective of the review was to evaluate the effectiveness of the
      use of phosphate binders on mortality and serum levels of phosphorus, calcium and
      parathyroid hormone in adult patients with end stage renal disease receiving
      hemodialysis compared to hemodialysis with no phosphate binder use. INTRODUCTION:
      End stage renal disease leading to hemodialysis is a common global health issue.
      Effective management of this population is focused on balancing alterations in
      bone mineral markers such as phosphorus, calcium and parathyroid hormone. Chronic
      imbalances are associated with all-cause mortality. Phosphate binders are a
      crucial element to regulating these levels. INCLUSION CRITERIA: The review
      considered studies including adult patients, age 18 and over receiving
      hemodialysis. The intervention of interest was the use of any drug within the
      class of phosphate binders. Outcomes of interest were all-cause mortality and
      serum levels of phosphorus, calcium, and parathyroid hormone. Experimental and
      quasi-experimental study designs were considered. METHODS: A search for relevant
      published and unpublished literature was conducted through November 5, 2017.
      Databases searched included PubMed, CINAHL, Embase and Cochrane Central Register
      of Controlled Trials (CENTRAL), in addition to gray literature sources. Articles
      that met the inclusion criteria were further assessed for methodological validity
      by two independent reviewers using the standard critical appraisal instruments
      from Joanna Briggs Institute. Data were extracted from papers included in the
      review using the standardized data extraction tool from the Joanna Briggs
      Institute. Quantitative data were pooled for statistical meta-analysis to
      evaluate the impact of phosphate binders on phosphorus and calcium. RESULTS:
      Seven studies were included in this review. A meta-analysis of four studies
      showed that the use of phosphate binders resulted in a statistically significant
      decrease in phosphorus levels compared to placebo (mean difference -1.89 mg/dL,
      95% confidence interval -2.03 mg/dL, -1.75 mg/dL); three additional studies
      described narratively also showed a statistically significant decrease in
      phosphorus. A meta-analysis of three studies showed a statistically significant
      increase in calcium compared to placebo (mean difference 0.57 mg/dL, 95%
      confidence interval 0.50 mg/dL, 0.64 mg/dL); two additional studies described
      narratively showed no difference in effect on calcium. Of the three studies that
      measured parathyroid hormone, one showed a statistically significant improvement
      with the use of phosphate binders (mean difference -83.0 pg/mL, 95% confidence
      interval -154.63 pg/mL, -11.37 pg/mL) and two showed no difference in effect. No
      studies measured mortality. CONCLUSION: Phosphate binders are effective in
      reducing serum phosphorus. The findings on parathyroid hormone and calcium did
      not provide adequate support for phosphate binder use. The impact on mortality
      was not directly measured in any of the included studies.

PMID- 30204712
TI  - Electronic textile electrocardiogram monitoring in cardiac patients: a scoping
      review protocol.
AB  - REVIEW QUESTION/OBJECTIVE: This scoping review aims to explore and scope the
      literature and research on the use of e-textile electrocardiogram (ECG)
      monitoring in cardiac patients and provide a unique contribution to the available
      evidence. The objectives of this scoping review are:The questions of this review
      are.

PMID- 30204714
TI  - Effectiveness of strategies and interventions that aim to assist the transition
      from student to newly qualified nurse: an update systematic review protocol.
AB  - REVIEW QUESTION/OBJECTIVE: The objective of this systematic review update is to
      evaluate recent available research on the effectiveness of strategies and
      interventions that aim to assist the transition from student to newly qualified
      nurse on job satisfaction, confidence, competence, knowledge, stress, anxiety,
      retention, turnover and costs.

PMID- 30204713
TI  - Impact of mobile health interventions during the perinatal period for mothers in
      low- and middle-income countries: a systematic review protocol.
AB  - REVIEW QUESTION: The objective of this review is to determine the impact of
      mother-targeted mobile health (mHealth) education interventions available during
      the perinatal period in low- and middle-income countries on maternal and newborn
      outcomes. Thus, the review questions are: what is the impact of mother-targeted
      mHealth education interventions on.

PMID- 30204715
TI  - Effectiveness of non-pharmacological and non-surgical interventions on the impact
      of rheumatoid arthritis: an umbrella review protocol.
AB  - REVIEW QUESTION: The questions of this review are.

PMID- 30204716
TI  - Reliability, validity and generalizability of multidimensional pain assessment
      tools used in postoperative adult patients: a systematic review protocol.
AB  - REVIEW QUESTION/OBJECTIVE: The objective of this review is to evaluate the
      measurement properties (reliability, validity and generalizability) of the
      multidimensional pain assessment tools that are used to assess postoperative pain
      in adults.

PMID- 30204717
TI  - Unique Circulating MicroRNA Profiles in HIV Infection.
AB  - OBJECTIVE: MicroRNAs (miRNAs) are noncoding RNAs that regulate gene expression.
      We aimed to determine the association between extracellular miRNAs and HIV
      infection. DESIGN: Single-center, cross-sectional study. METHODS: We analyzed the
      expression of 192 plasma-derived miRNAs in 69 HIV-infected individuals and 24
      uninfected controls using TaqMan miRNA assays and a high-throughput Real-Time PCR
      instrument (Fluidigm). False discovery rate (FDR) was applied. RESULTS: HIV
      infected individuals and controls were similar in age, sex, and traditional risk
      factors. Among those with HIV, 72.5% were on antiretroviral therapy (ARVs) and
      64% had an undetectable viral load. Twenty-nine miRNAs were differentially
      expressed in the plasma of HIV-infected individuals compared with controls (P <
      0.05, FDR < 0.15). Nineteen miRNAs were differentially expressed among HIV+
      subjects on ARVs, HIV+ subjects not on ARVs, and HIV- subjects (P < 0.05 and FDR
      < 0.15). Thirty-four miRNAs were differentially expressed between HIV- subjects
      and elite controllers (ie, suppressed viral loads despite the absence of ARVs; P
      < 0.05 and FDR < 0.15). These 34 miRNAs included miRs-29c, 146b, 223, and 382,
      which were previously reported to have intracellular roles in HIV latency, as
      well as miRs-126, 145, and let-7, which were previously shown to be
      differentially expressed in coronary artery disease among uninfected individuals.
      CONCLUSIONS: We demonstrate a unique expression profile of 29 miRNAs in HIV+
      subjects and 34 miRNAs in elite controllers as compared to HIV- subjects. These
      miRNA signatures may be useful in further elucidating mechanisms of viral and
      immunological control and may have diagnostic or prognostic value in HIV
      associated coronary artery disease.

PMID- 30204718
TI  - Brief Report: Hyperbilirubinemia Is Associated With a Decreased Risk of Carotid
      Atherosclerosis in HIV-Infected Patients on Virological Suppression.
AB  - OBJECTIVE: To investigate the association between total, direct, and indirect
      bilirubin and the presence of carotid lesions in a large sample of HIV-1-infected
      patients on virological suppression. DESIGN: Retrospective study on adult HIV-1
      infected patients, with a carotid ultrasound (CUS) examination performed between
      January 2008 and August 2016, with HIV-RNA <50 copies per milliliter at CUS and
      without previous cardiovascular events. METHODS: Intima media thickness was
      measured in 4 segments: carotid common artery and bifurcation on the left and
      right sides. Carotid lesion was defined as an intima media thickness >=1.5 mm in
      >=1 region at CUS. Patients were classified as: normal if all bilirubin values
      before CUS were below the upper normal limit and with hyperbilirubinemia if >=1
      bilirubin value above upper normal limit before CUS was recorded. Multivariate
      logistic regression was used to determine whether hyperbilirubinemia showed
      association with the presence of >=1 carotid lesion, after adjusting for
      confounding factors. RESULTS: Overall, 903 patients were evaluated, 511 with >=1
      and 392 without carotid lesions. At multivariate analysis, total [adjusted odds
      ratio (95% confidence interval) 0.57 (0.36 to 0.90), P = 0.016] and indirect
      hyperbilirubinemia before CUS [adjusted odds ratio (95% confidence interval) 0.62
      (0.40 to 0.97), P = 0.036] were associated with a lower risk of carotid lesions
      in addition to younger age, negative hepatitis C virus antibodies, higher nadir
      CD4, lower low-density lipoprotein cholesterol, higher high-density lipoprotein
      cholesterol, lower triglycerides, and no use of statin; no effect of atazanavir
      treatment on carotid lesions was detected. CONCLUSIONS: In HIV-1-treated
      patients, total or indirect hyperbilirubinemia was likely associated with the
      absence of carotid lesions.

PMID- 30204720
TI  - Brief Report: Integration of PrEP Services Into Routine Antenatal and Postnatal
      Care: Experiences From an Implementation Program in Western Kenya.
AB  - BACKGROUND: Programmatic approaches for delivering pre-exposure prophylaxis
      (PrEP) to pregnant and postpartum women in settings with high HIV burden are
      undefined. The PrEP Implementation for Young Women and Adolescents (PrIYA)
      Program developed approaches for delivering PrEP in maternal child health (MCH)
      clinics. METHODS: Under the PrIYA Program, nurse-led teams worked with MCH staff
      at 16 public, faith-based, and private facilities in Kisumu, Kenya, to determine
      optimal clinic flow for PrEP integration into antenatal care (ANC) and postnatal
      care (PNC). A program-dedicated nurse facilitated integration. HIV-uninfected
      women were screened for behavioral risk factors; same-day PrEP was provided to
      interested and medically eligible women. PrEP and MCH services were evaluated
      using standardized flow mapping and time-and-motion surveys. RESULTS: Clinics
      developed 2 approaches for integrating PrEP delivery within ANC/PNC: (1) co
      delivery: ANC/PNC and PrEP services delivered by same MCH nurse or (2) sequential
      services: PrEP services after ANC/PNC by a PrEP-specialized nurse. Three clinics
      selected co-delivery and 13 sequential services, based on patient volume and
      space availability. Overall, 86 ANC/PNC visits were observed. Clients who
      initiated PrEP took a median of 18 minutes (interquartile range 15-26) for PrEP
      related activities (risk assessment, PrEP counseling, creatinine testing,
      dispensation, and documentation) in addition to other routine ANC/PNC activities.
      For clients who declined PrEP, an additional 13 minutes (interquartile range 7
      15) was spent on PrEP-related risk assessment and counseling. CONCLUSIONS: PrEP
      delivery within MCH used co-delivery or sequential approaches. The moderate
      additional time burden for PrEP initiation in MCH would likely decline with
      community awareness and innovations such as group/peer counseling or expedited
      dispensing.

PMID- 30204719
TI  - Impact of Patient-Provider Attachment on Hospital Readmissions Among People
      Living With HIV: A Population-Based Study.
AB  - BACKGROUND: Hospital readmission 30 days after discharge is associated with
      adverse health outcomes, and people living with HIV (PLWH) experience elevated
      rates of hospital readmission. Although continuity of care with a health care
      provider is associated with lower rates of 30-day readmission among the general
      population, little is known about this relationship among PLWH. The objective of
      this study is to examine whether engaging with the same provider, defined as
      patient-provider attachment, is associated with 30-day readmission for this
      population. SETTING: Data were derived from the Seek and Treat for Optimal
      Prevention of HIV in British Columbia cohort. METHODS: Using generalized
      estimating equation with a logit link function, we examined the association
      between patient-provider attachment and 30-day hospital readmission. We
      determined whether readmission was due to all cause or to a similar cause as the
      index admission. RESULTS: Seven thousand thirteen PLWH were hospitalized during
      the study period. Nine hundred twenty-one (13.1%) were readmitted to hospital for
      all cause and 564 (8.0%) for the similar cause as the index admission. Patient
      provider attachment was negatively associated with 30-day readmission for all
      causes (adjusted odds ratio = 0.85, confidence interval = 0.83 to 0.86). A second
      multivariable model indicated that patient-provider attachment was also
      negatively associated with 30-day readmission for a similar cause (adjusted odds
      ratio = 0.86, confidence interval = 0.84 to 0.88). CONCLUSIONS: Our results
      indicate that a higher proportion of patient-provider attachment was negatively
      associated with 30-day hospital readmission among PLWH. Our study findings
      support the adoption of interventions that seek to build patient-provider
      relationships to optimize outcomes for PLWH and enhance health care
      sustainability.

PMID- 30204721
TI  - Association of HIV Suppression With Kidney Disease Progression Among HIV-Positive
      African Americans With Biopsy-Proven Classic FSGS.
AB  - BACKGROUND: In the era of combined antiretroviral therapy, classic focal
      segmental glomerulosclerosis (FSGS) is the most common histopathological finding
      in African American HIV-positive patients with kidney disease. We sought to
      determine whether HIV suppression is associated with lower risk of progression to
      end-stage renal disease (ESRD) among HIV-positive African Americans with biopsy
      confirmed classic FSGS. METHODS: HIV-positive African Americans who underwent
      kidney biopsies at a single tertiary hospital between January 1996 and June 2011
      were confirmed as having classic FSGS by the presence of segmental
      glomerulosclerosis without features of HIV-associated nephropathy. Multivariable
      Cox proportional hazards models were used to examine the independent association
      of viral suppression (HIV-RNA < 400 copies per milliliter at biopsy) with time to
      progression to ESRD. RESULTS: Of the 55 HIV-positive African Americans with
      classic FSGS, 26 had suppressed viral loads at the time of biopsy. Compared to
      viremic patients, those who were virally suppressed had a significantly higher
      mean CD4 cell count (452 vs. 260 cell/mm, respectively; P = 0.02) and median
      estimated glomerular filtration rate (53.5 vs 35.5 mL/min/1.73 m, respectively; P
      = 0.002). Adjusting for sex and baseline CD4 cell count, estimated glomerular
      filtration rate, and proteinuria, those with HIV-RNA levels <400 copies per
      milliliter at baseline had a 75% lower risk of progressing to ESRD (hazard ratio
      = 0.25; 95% CI: 0.07 to 0.88) during a median follow-up time of 2.70 years
      (interquartile range: 0.80-5.15 years). CONCLUSIONS: HIV suppression is
      associated with significantly lower risk of progression to ESRD among HIV
      infected African Americans with classic FSGS, supporting the potential role of
      combined antiretroviral therapy for this histopathology in addition to HIV
      associated nephropathy among HIV-positive individuals.

PMID- 30204723
TI  - The prognostic and diagnostic value of 18F-FDG PET/CT for assessment of
      symptomatic osteoarthritis: Erratum.

PMID- 30204722
TI  - Advancing HIV Biomedical Prevention Research for At-Risk Adolescents.
AB  - Despite significant additions to the HIV prevention toolbox, infection rates
      across the United States continue to rise among vulnerable adolescents and young
      adults. Access to these interventions by youth at risk for HIV is limited by the
      lack of data about their safety and use, compounding the myriad contextual
      barriers to effectively preventing HIV in this group. The NIH-funded Adolescent
      Trials Network implemented an innovative approach to the inclusion of adolescents
      at risk for HIV infection who consented for their own participation in the first
      adolescent study of HIV pre-exposure prophylaxis (PrEP). This model of mature
      minor consent was supported by state-based adolescent treatment statutes that
      extend an adolescent's ability to consent to participation in research with a
      sufficient prospect of clinical benefit from the intervention to justify the
      potential risks, and a balance of benefits and risks that is at least as
      favorable as available evidence-based alternatives. Important data on the safety
      and patterns of PrEP use by at-risk adolescents prompted the FDA to revise the
      label. The expanded indication of PrEP for HIV prevention in adolescents is hoped
      to inform clinical guidelines and provides a powerful tool to reduce new
      infections in the United States among vulnerable at-risk adolescents. Lessons
      learned from this years-long iterative endeavor have implications for improving
      access to the rapidly evolving landscape of HIV prevention modalities, including
      recently implemented studies of long-acting PrEP formulations designed to reduce
      the burden of daily adherence required by oral PrEP, a major clinical pitfall for
      adolescent clinicians and their patients.

PMID- 30204724
TI  - The Rules of Attractiveness: A Study on the Lower Facial Third.
AB  - What is considered attractive may not fall into the "norm," and it can vary from
      culture to culture and depending on the historical time, for this reason the
      standard cephalometric and antropometric references may not be sufficient in
      these cases.Lately some techniques have arose to popularity that are aimed to
      changing the frontal and lateral aspect of the facial lower third, such as V-line
      or the Chin-Wing Osteotomy technique, but no reference system exists at the
      moment to define to which extent a modification of the lower third falls within
      what is considered beautiful, and everything is left to the patient's will or to
      the surgeon's sensitivity.The aim of this article is to study which antropometric
      value is considered attractive by the most for what concerns the frontal shape of
      the lower third of the face.Twenty-four female models were enrolled in this study
      and the angle taken into consideration was the one at the intersection between
      the 2 lines connecting the cutaneous gonial angle of each side of the face and
      the most external part of the chin on the same side. Measures were made on
      pictures in frontal view.Two hundred two random examiners were asked to see the
      pictures and rate them as attractive or nonattractive.Results were then paired
      with the angles values.Among the models the higher angle measured was 107.5
      degrees  (found in 1 individual) while the lower angle was 76 degrees  (found in
      1 individual), the average measure calculated was 88.3 degrees  while the median
      angle was 89.5 degrees .According to the result the subjects considered more
      attractive were those with an angle between 84.5 and 91.5 (92 for male
      examiners).This could be an important starting point for studies who can evaluate
      attractiveness from a numerical point of view.

PMID- 30204725
TI  - Comparison of Musculocutaneous and Fasciocutaneous Free Flaps for the
      Reconstruction of the Extensive Composite Scalp and Cranium Defects.
AB  - Composite scalp and cranium defects, which require microsurgical reconstruction,
      result from tumor resection, radiation, trauma, severe burn injuries, and rarely
      vasculitic disorders. In the current study, the authors aim to compare the
      outcomes of the fasciocutaneous flaps and musculocutaneous free flaps used for
      the reconstruction of extensive composite scalp and cranium defects. From 2010 to
      2017, 21 patients who underwent composite scalp and cranium defect reconstruction
      with a free flap were retrospectively identified. Eighteen patients had squamous
      cell carcinoma, 2 patients had meningioma, and 1 patient had Ewing sarcoma.
      Thirteen musculocutaneous free flaps including latissimus dorsi and vertical
      rectus abdominis flaps and 9 free fasciocutaneous flaps including radial forearm
      and anterolateral thigh flaps were used. Only 1 flap loss was encountered. No
      neurologic impairment in postoperative period was reported. The mean length of
      stay in the hospital, the duration of surgery, and total volume of blood
      transfusion for the fasciocutaneous flap group were significantly shorter than
      those for musculocutaneous flap group. No flap atrophy was reported in
      fasciocutaneous flap group. Reconstruction of the composite scalp and cranium
      defects with fasciocutaneous free flaps allows shorter hospitalization, less
      blood transfusion and less flap atrophy than those of musculocutaneous flaps. To
      this respect, their usage should be prioritized in such challenging patients.

PMID- 30204726
TI  - Use of Recombinant Human Bone Morphogenetic Protein-2 Associated With Lyophilized
      Bovine Bone in Reconstruction of Atrophic Maxilla.
AB  - Cases of severely atrophic edentulous maxilla require reconstruction techniques
      employing bone grafts to promote adequate bone dimension for the successful
      placement of dental implants for prosthetic rehabilitation that reestablishes the
      patient's function and aesthetics. This study aims to present a severely atrophic
      edentulous maxilla reconstruction with the off-label use of recombinant human
      bone morphogenetic protein type 2 (rhBMP-2) associated with lyophilized
      particulate bovine bone xenograft for the prosthetic rehabilitation with
      osseointegrable dental implants. The paper describes a case of severely atrophic
      edentulous maxilla in a 42-year-old woman referred to the dental school with
      complaint of failure in adaptating to the dentures. The patient reported 27 years
      of maxilla edentulism and consecutive treatment failures, so the proposed therapy
      was the reconstruction of the maxilla with an association of rhBMP-2 and
      lyophilized bovine bone xenograft for increasing bone volume and further
      prosthetic rehabilitation with osseointegrated dental implants. The present
      report illustrates a case of atrophic edentulous maxilla in which the off-label
      use of rhBMP-2 was successful and the patient's prosthetic rehabilitation could
      be concluded. The 8 dental implants received prosthetic functional load during 1
      year of follow-up with no complications. Based on the case presented, the
      association between rhBMP-2 and a bovine bone xenograft could be considered a
      viable option for the reconstruction of atrophic edentulous maxilla. After a year
      of functional prosthetic load follow-up, the patient is asymptomatic and
      satisfactorily adaptated to the prosthesis, which restored her functional and
      aesthetic demands.

PMID- 30204727
TI  - CLINICAL CHARACTERIZATION OF STARGARDT DISEASE PATIENTS WITH THE p.N1868I ABCA4
      MUTATION.
AB  - PURPOSE: To investigate the Stargardt disease phenotype associated with an
      unusually common and "extremely hypomorphic" ABCA4 variant, p.N1868I. METHODS:
      The charts of 27 patients with p.N1868I on one allele and a severe/deleterious
      mutation on the other allele were reviewed. Subjective age of onset, best
      corrected visual acuity, and stage of disease were recorded for all 27 patients,
      18 of whom had multiple visits. When available, fundus photography, spectral
      domain optical coherence tomography, fundus autofluorescence, full-field
      electroretinograms, Goldmann visual fields, and fluorescein angiography were
      included. Five families with multiple affected members were analyzed. RESULTS:
      The median age at symptom onset was 41.5 years, and 3 p.N1868I patients had not
      developed visual symptoms as of the most recent eye examination. Median best
      corrected visual acuity in the better-seeing eye at baseline was 20/25, and the
      median duration from symptom onset to legal blindness was 25 years. The five
      families described in this study demonstrated clinically significant
      intrafamilial variability, and affected family members who did not share the
      p.N1868I variant had relatively more severe phenotypes. CONCLUSION: This study
      demonstrates the consistency of foveal sparing, the variation in age at onset,
      the intrafamilial variability, and the prognosis with regard to visual acuity in
      p.N1868I-associated Stargardt disease.

PMID- 30204728
TI  - OPHTHALMIC VASCULAR EVENTS AFTER INTRA-ARTERIAL CHEMOTHERAPY FOR RETINOBLASTOMA:
      Real-World Comparison Between Primary and Secondary Treatments.
AB  - PURPOSE: To determine whether treatment order affects ophthalmic vascular event
      rates after intra-arterial chemotherapy (IAC) for retinoblastoma. METHODS:
      Patients who received IAC as primary or secondary treatment for retinoblastoma
      from January 2009 to January 2018 were included. All eyes were imaged with fundus
      photography and fluorescein angiography. Patient characteristics and vascular
      event rates were compared using t-test and Fisher's exact test. RESULTS: There
      were 196 patients treated with 682 infusions of IAC, divided into primary (no
      previous therapy, 98 eyes of 98 patients, 328 infusions) and secondary (after
      other therapy, 105 eyes of 98 patients, 354 infusions) treatment. Overall,
      ophthalmic vascular events were found after 5% of infusions (17% eyes). A
      comparison of ophthalmic vascular events (primary vs. secondary IAC), with mean
      three infusions per eye (median 3, range 1-7), revealed no difference in overall
      percentage of eyes affected (18% vs. 15%, P = 0.57). Adverse vascular events per
      eye included retinal vasculature attenuation (1% vs. 0%, P = 0.99), peripheral
      retinal pruning (1% vs. 0%, P = 0.99), branch retinal artery occlusion (0% vs.
      1%, P = 0.99), central retinal artery occlusion (0% vs. 1%, P = 0.99), macular
      ischemia (0% vs. 2%, P = 0.51), vitreous hemorrhage (2% vs. 3%, P = 0.92),
      subretinal hemorrhage (1% vs. 0%, P = 0.99), retinal pigment epithelium atrophy
      (6% vs. 3% P = 0.43), choroidal atrophy (4% vs. 2%, P = 0.92), optic disk pallor
      (1% vs. 0%, P = 0.99), and ophthalmic artery occlusion (9% vs. 6%, P = 0.35).
      CONCLUSION: Ophthalmic vascular events after IAC for retinoblastoma affect only
      5% of eyes per infusion (17% of treated eyes). Vascular event risk per eye is
      similar when using IAC as primary or secondary treatment.

PMID- 30204729
TI  - FACEDOWN POSITIONING AFTER VITRECTOMY WILL NOT FACILITATE MACULAR HOLE CLOSURE
      BASED ON SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY IMAGING IN GAS-FILLED EYES: A
      Prospective, Randomized Comparative Interventional Study.
AB  - PURPOSE: To compare clinical outcomes in eyes with macular hole (MH) managed by
      either facedown (FD) or no-FD (nFD) postoperative positioning protocols. METHODS:
      This is a prospective randomized cohort study. Eighty eyes of 80 consecutive
      patients with MH who had undergone vitrectomy surgery with internal limiting
      membrane peeling and gas tamponade were included in this study. Forty eyes of 40
      patients who were kept in FD position for 3 days after surgery were assigned to
      the FD group, 40 eyes of 40 patients with nFD positioning were assigned to the
      nFD group. Macular hole was examined with swept-source optical coherence
      tomography images at 1 day, 2 days, 3 days, 2 weeks, 1 month, and 3 months after
      surgery. The MH closure rate and change of best-corrected visual acuity were
      compared. RESULTS: At postoperative Day 1, MH was closed in 24 of 32 eyes (with
      clear optical coherence tomography images) (75%) in the FD group and 23 of 30
      eyes (with clear optical coherence tomography images) (77%) in the nFD group (P =
      0.97). At postoperative Day 2, MH closure was confirmed in 32 of 36 eyes (88.9%)
      in the FD group and in 31 of 33 eyes (94%) in the nFD group (P = 0.84), and the
      results were unchanged at Day 3. At 2 weeks after surgery, clear optical
      coherence tomography images were acquired from all eyes in both groups, and MH
      closure was confirmed in 36 of 40 eyes (90%) in the FD group and in 37 of 40
      (92.5%) eyes in the nFD group (P = 0.91). Macular hole closure was not achieved
      in eyes that were kept open by Day 3 after surgery, and none of the eyes with
      confirmed MH closure by Day 3 had a reopening of the MH by 3 months. The
      distribution of macular configuration at 3 months was not significantly different
      between the two groups (P = 0.96). There was no difference in terms of the
      improvement in best-corrected visual acuity (Early Treatment Diabetic Retinopathy
      Study letters gain) between the 2 groups at 1 month (P = 0.22) and 3 months (P =
      0.45). CONCLUSION: The nFD protocol neither delayed the MH closure nor decreased
      the final closure rate after vitrectomy surgery. Therefore, postoperative prone
      position seems to be unnecessary for all MH repair procedures.

PMID- 30204730
TI  - RANIBIZUMAB VERSUS VERTEPORFIN PHOTODYNAMIC THERAPY IN ASIAN PATIENTS WITH MYOPIC
      CHOROIDAL NEOVASCULARIZATION: BRILLIANCE, a 12-Month, Randomized, Double-Masked
      Study.
AB  - PURPOSE: To evaluate the efficacy and safety of 2 dosing regimens of ranibizumab
      0.5 mg versus verteporfin photodynamic therapy in Asian patients with visual
      impairment due to myopic choroidal neovascularization. METHODS: Eligible patients
      (aged >=18 years) were randomized 2:2:1 to Group I (n = 182; ranibizumab
      treatment guided by visual acuity stabilization criteria); Group II (n = 184;
      ranibizumab treatment guided by disease activity); or Group III (n = 91;
      verteporfin photodynamic therapy on Day 1; from Month 3, ranibizumab/verteporfin
      photodynamic therapy/both treatment guided by disease activity). RESULTS: The
      mean average best-corrected visual acuity change from baseline to Month 1 through
      Month 3 was significantly higher in Groups I/II versus Group III (Group I/II:
      +9.5/+9.8 letters vs. Group III: +4.5 letters; both P < 0.001). Group II was
      statistically noninferior to Group I for the mean average best-corrected visual
      acuity change from baseline to Month 1 through Month 6 (10.7 vs. 10.4 letters; P
      < 0.001). Over 12 months, the mean number of ranibizumab injections received by
      Groups I/II/III was 4.6/3.9/3.2. CONCLUSION: In Asian patients, ranibizumab
      treatments demonstrated superior efficacy versus verteporfin photodynamic therapy
      at Month 3, and the beneficial treatment effects persisted at Month 12.
      Ranibizumab was well-tolerated and demonstrated a good safety profile.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- 30204731
TI  - INNER MACULAR CHANGES AFTER VITRECTOMY WITH INTERNAL LIMITING MEMBRANE PEELING
      FOR RHEGMATOGENOUS RETINAL DETACHMENT: Similarity With Alport Syndrome.
AB  - PURPOSE: The internal limiting membrane (ILM), the innermost basement membrane of
      the retina, is peeled occasionally during vitreous surgery. This study aimed to
      investigate the effect of ILM loss on the retina. METHODS: We used optical
      coherence tomography to retrospectively evaluate retinal changes in 26 eyes (11
      ILM-peeled and 15 ILM-unpeeled eyes) of 26 patients after vitrectomy for retinal
      detachment. In addition, we studied six eyes of three patients with Alport
      syndrome, in which ILM is genetically impaired. RESULTS: We observed significant
      inner retinal displacement of the foveal pit toward the optic disk with inner
      retinal thickening in the nasal area (fellow, 191.9 +/- 24.3 MUm vs. affected,
      210.3 +/- 31.4 MUm; P = 0.048), inner retinal thinning in the temporal area
      (fellow, 174.3 +/- 18.3 MUm vs. affected, 142.2 +/- 23.6 MUm; P < 0.001), foveal
      thickening (ILM-unpeeled, 217.0 +/- 39.4 MUm vs. ILM-peeled, 302.0 +/- 86.2 MUm;
      P = 0.006), inner retinal dimples predominantly in the temporal area, and
      deviation between the foveal pit and foveal bulge. Eyes with Alport syndrome
      exhibited similar findings. CONCLUSION: Internal limiting membrane loss seems to
      cause characteristic inner retinal changes of the macula in both congenital and
      acquired conditions.

PMID- 30204732
TI  - MYD88 L265P MUTATION DETECTION IN THE AQUEOUS HUMOR OF PATIENTS WITH
      VITREORETINAL LYMPHOMA.
AB  - PURPOSE: To detect the presence of MYD88 L265P mutation in the aqueous humor of
      patients with cytologically proven vitreoretinal lymphoma. METHODS: Eight
      consecutive patients with bilateral vitreoretinal lymphoma (16 eyes) were
      prospectively evaluated. Genomic DNA was extracted from aqueous samples after
      paracentesis and vitreous humor samples after diagnostic vitrectomy. MYD88 codon
      265 mutation was investigated by both amplification-refractory mutation system
      polymerase chain reaction approach and pyrosequencing assay in the aqueous humor
      of all patients and in the vitreous of 6 patients. A control group of 8 age
      matched patients with established diagnosis of noninfectious uveitis was also
      tested for the presence of MYD88 L265P mutation in the aqueous humor. RESULTS:
      Eight patients (three men, five women) with mean age of 69.5 years (range 50-85
      years) were considered. All the patients tested for MYD88 L265P in the vitreous
      (six) were positive, and this result was consistent with cytological examination
      in all samples but one. The MYD88 L265P mutation was found in the aqueous of 6
      patients (75%), and in 3 of them, the mutation was present in both eyes. Results
      of MYD88 L265P mutation in aqueous and vitreous sample were consistent in 7 of
      the 8 eyes with available samples. The aqueous humor of the noninfectious uveitis
      control group was negative for the detection of MYD88 L265P mutation. CONCLUSION:
      MYD88 mutation was detected in the aqueous humor of 75% of patients with
      cytologically proven vitreoretinal lymphoma. This technique may be considered as
      an additional diagnostic tool in the detection of the disease.

PMID- 30204733
TI  - Mixing of Injectable Fillers: A National Survey.
AB  - BACKGROUND: The mixing of hyaluronic acid or calcium hydroxylapatite fillers with
      normal saline, plain lidocaine, or lidocaine with epinephrine before injection is
      a familiar practice among dermatologists. However, the frequency of this practice
      and rationale behind it has not been well studied. OBJECTIVE: To better elucidate
      the clinical practice of mixing fillers with other solutions before injecting
      among dermatologists. METHODS: A survey was electronically distributed to members
      of the American Society for Dermatologic Surgery. RESULTS: Four hundred seventy
      five dermatologists responded to the survey. Thirty-five percent of respondents
      mix fillers before injection. Solutions used were as follows: plain lidocaine
      (44%), lidocaine with epinephrine (36%), normal saline (30%), and sterile water
      (7%). Respondents mix filler for the following reasons: to decrease viscosity
      (40%), increase anesthesia (30%), decrease swelling (17%), and increase volume
      (13%). CONCLUSION: Despite the lack of evidence, more than one-third of
      dermatologists surveyed mix fillers with other solutions before injection. Plain
      lidocaine is most commonly used. The top reason for mixing fillers is to decrease
      viscosity and facilitate ease of injection. More scientific data are needed to
      support this practice and better understand the biophysical changes that occur
      when mixing fillers with other solutions.

PMID- 30204734
TI  - Effect of Vitamin D Deficiency on Hypertrophic Scarring.
AB  - BACKGROUND: Although many different diseases have been reported with vitamin D
      deficiency, the authors failed to find any studies on the association of
      hypertrophic scarring (HS) in the literature. OBJECTIVE: The authors aimed to
      determine the relationship between vitamin D deficiency and HS and investigate
      the effect of replacement therapy on HS development in patients with vitamin D
      deficiency. PATIENTS AND METHODS: Patients who presented to the authors'
      outpatient clinic with HS between 2013 and 2016 were included in the study. In
      the first stage, all the patients with HS complaints were assessed for vitamin D
      levels. In the second stage, 50 patients with a vitamin D level less than 25
      ng/mL and a linear scar after at least 1 year of trauma were randomly divided
      into 3 groups. Group 1: patients who did not accept any medical or surgical
      treatment; Group 2: patients who were subjected to vitamin D replacement only;
      Group 3: patients who underwent surgical excision and suturation after vitamin D
      replacement. RESULTS: A statistically significant correlation was found between
      HS and vitamin D levels (p < .05). A statistically significant decrease in scar
      width was observed in Group 3 (p < .05). CONCLUSION: Increasing vitamin D levels
      to above 25 ng/mL before scar revision and vitamin D deficiency in patients with
      HS may help reduce scar width.

PMID- 30204735
TI  - Computer-Based Video Instruction for Training Medical Students on Skin Biopsies.
AB  - BACKGROUND: The development of procedural skills is necessary for medical
      students. Computer-based video instruction (CBVI) increases knowledge and
      procedural skills. OBJECTIVE: This pilot study's aim was to investigate the
      usefulness of CBVI in dermatologic procedure training for medical students and
      secondarily assess students' overall perception of the field of dermatology.
      METHODS: Twenty-nine first- and second-year medical students were randomly
      assigned to the CVBI group or control group, in addition to in-person instructor
      demonstration of shave and punch biopsies using fresh cadaver tissue. Blinded
      evaluators graded student performances using a five-point Likert scale
      immediately after demonstration, and 1 week later to assess knowledge retention.
      RESULTS: In overall performance, the CBVI group demonstrated higher scores both
      in shave (3.54 vs 2.59, p = .01) and punch biopsies (3.63 vs 2.88, p = .01) at
      immediate recall and knowledge retention (3.68 vs 2.67, p = .01; 4.00 vs 2.99, p
      < .001, respectively). Approximately 33.3% of the students stated that the
      experience increased their interest in the field of dermatology. CONCLUSION:
      Incorporation of CBVI into the dermatology curriculum augments medical students'
      procedural skills. The CBVI group performed significantly better in all 7 grading
      categories for shave biopsy and in 5 of 7 categories for punch biopsy.
      Integration of procedural laboratory tests raises students' interest in
      dermatology.

PMID- 30204736
TI  - Methods of Standardizing Photography for Cellulite in the Buttocks and Thighs.

PMID- 30204737
TI  - Recognition of Alkaptonuria During Mohs Micrographic Surgery.

PMID- 30204738
TI  - In the Crosshairs: Loss of Vellus Hair Follicles in Basal Cell Carcinoma. A Clue
      to Clinical Margin.

PMID- 30204740
TI  - Epidermolysis Bullosa Patients' Perception of Surgical Wound and Scar Healing.
AB  - BACKGROUND: There is limited evidence to suggest patients with epidermolysis
      bullosa (EB) have more postoperative wound complications than the general
      population. Despite this, the authors have noted reluctance among some surgeons
      to operate on these patients. OBJECTIVE: A cross-sectional study was designed to
      investigate postoperative wound and scar healing outcomes in patients with EB.
      METHODS: Patients were asked to complete the "Surgical Wound and Scar Healing in
      EB" questionnaire, and data gathered were analyzed. RESULTS: Forty-six patients
      completed the questionnaire for a total of 94 different surgical procedures. Five
      patients reported blistering at the surgical wound site. All 5 had generalized
      forms of EB. Four patients reported wound infections, and 1 patient reported
      wound dehiscence. The postoperative scar healed with keloid or hypertrophic
      scarring after 26% of the reported surgical procedures. CONCLUSION: Blistering at
      the postoperative site seems to be uncommon and particularly unlikely to occur in
      localized forms of EB. Postoperative wound infections and dehiscence are
      uncommon. Patients with EB may have a propensity to develop keloid or
      hypertrophic scarring. With these data, the authors hope clinicians have greater
      confidence in referring patients with EB for surgery, and surgeons more reassured
      about postoperative wound healing.

PMID- 30204739
TI  - Efficacy, Safety, and Subject Satisfaction After AbobotulinumtoxinA Treatment of
      Upper Facial Lines.
AB  - BACKGROUND: Botulinum toxins are the treatment of choice for wrinkles in the
      upper third of the face. OBJECTIVE: The purpose of this study was to evaluate the
      efficacy, safety, and subject satisfaction of abobotulinumtoxinA (ABO) for
      treatment of upper facial lines. MATERIALS AND METHODS: Subjects aged 35 to 50
      years with moderate-to-severe upper facial lines were included in this study.
      Subjects received a maximum of 125 s.U. ABO in at least 2 indications with
      optional touch-up after 2 weeks. Assessments included wrinkle severity, global
      aesthetic improvement, subject satisfaction, and adverse events (AEs) 1, 3, and 6
      months after treatment. RESULTS: At Month 1, 100, 94, and 93% of subjects were
      responders in dynamic glabellar, lateral canthal, and forehead lines,
      respectively. All subjects were improved 1 month after treatment, and the
      majority of the subjects were still improved after 6 months. After treatment,
      most subjects were satisfied with the appearance of their face, felt better about
      themselves, and agreed that the treatment made them look the way they feel. Seven
      subjects (22%) had 8 ABO-related AEs (mild-moderate); headache was most commonly
      reported (9%). CONCLUSION: AbobotulinumtoxinA effectively treated upper facial
      lines, with high patient satisfaction. Treatment was generally well-tolerated.

PMID- 30204741
TI  - Randomized Controlled Trial of Preoperative Topical Decolonization to Reduce
      Surgical Site Infection for Staphylococcus aureus Nasal Swab-Negative Mohs
      Micrographic Surgery Patients.
AB  - BACKGROUND: Surgical site infection (SSI) is mainly due to endogenous bacteria.
      Topical decolonization is a preoperative intervention currently advised for
      proven nasal carriers of Staphylococcus aureus (S. aureus). OBJECTIVE: The
      authors assessed whether topical decolonization could be of benefit for patients
      who are not nasal carriers of S. aureus. METHODS AND MATERIALS: The authors
      performed a randomized controlled trial of S. aureus nasal swab-negative
      patients. Five days before Mohs surgery topical decolonization with nasal
      mupirocin and chlorhexidine, body wash was started. The control group had no
      intervention. RESULTS: In the week after Mohs surgery, the infection rate in the
      intervention group was 2% (n = 661, 14) and that of the control group was 4% (n =
      689, 29). CONCLUSION: Topical decolonization reduces SSI in nasal swab-negative
      Mohs surgery patients.

PMID- 30204742
TI  - Hidradenitis Suppurativa After Radical Surgery-Long-Term Follow-up for
      Recurrences and Associated Factors.
AB  - BACKGROUND: Hidradenitis suppurativa (HS) is a chronic debilitating skin disease
      in inverse body areas. Wide excision is recommended in Hurley Stages II to III,
      but the rate and symptoms of recurrences in long-term follow-up remain unclear.
      OBJECTIVE: To analyze the allocation of recurrences regarding the operative
      field, the onset and quality of HS symptoms as well as factors associated with
      recurrences in long-term follow-up. MATERIAL AND METHODS: Forty-eight patients
      with Hurley Stage III disease who had undergone 91 wide excisions from 2010 to
      2015 were clinically examined regarding postoperative complications and
      allocation and quality of recurrences. To determine the risk of recurrence,
      possible surgery, and lifestyle-related associated factors were investigated.
      RESULTS: Postoperative recurrences of HS were seen in 54.2%. Most recurrences
      (inflamed nodules) were detected in a <1-cm margin around the operative field
      (18.7%). Surgery under tumescence local anesthesia showed symptoms in 40.6%
      compared with 28.6% under general anesthesia. Increased alcohol consumption (p =
      .027) but not body mass index (p = .11) or smoking behavior (p = .45) had
      significant effect on relapse of HS. CONCLUSION: Caution must be given especially
      in surgery with local anesthesia only. Half of patients with HS showed long-term
      follow-up signs of recurrence after wide excision, most frequently nearby the
      operation field.

PMID- 30204743
TI  - Deoxycholic Acid for Submental Fullness and More: Real-World Experience With 202
      Patients.

PMID- 30204744
TI  - Stability of Hyaluronic Acid Fillers After Insulated Microneedle Radiofrequency
      Treatment.

PMID- 30204746
TI  - Multistate Syphilis Outbreak Among American Indians, 2013 to 2015.
AB  - This article summarizes a multistate outbreak of heterosexual syphilis, including
      134 cases of syphilis in adults and adolescents and at least 2 cases of
      congenital syphilis, which occurred on an American Indian reservation in the
      United States during 2013-2015. In addition to providing salient details about
      the outbreak, the article seeks to document the case-finding and treatment
      activities undertaken, their relative success or failure, and the lessons learned
      from a coordinated, multiagency response. Of 134 adult cases of syphilis, 40%
      were identified by enhanced, interagency contact tracing and partner services,
      26% through symptomatic testing, and 16% through screening of asymptomatic
      individuals as the result of an electronic medical record screening prompt. A
      smaller proportion of cases were identified by community screening events in high
      morbidity communities; high-risk venue-based screening events; other screening,
      including screening upon request; and prenatal screening at first trimester,
      third trimester, and day of delivery. Future heterosexual syphilis outbreak
      responders should act quickly to coordinate a package of high-yield case-finding
      and treatment activities-potentially including activities that seek to do the
      following: (1) increase prenatal screening, (2) improve community awareness and
      symptomatic test seeking, (3) educate providers and improve general screening for
      syphilis, (4) implement electronic medical record reminders for providers, (5)
      screen high-morbidity communities and at high-risk venues, and (6) form novel
      partnerships to accomplish partner services work when the context does not allow
      for traditional, disease intervention specialist-only partner services.

PMID- 30204745
TI  - Risk Factors for Oral Human Papillomavirus Infection Among Young Men Who Have Sex
      With Men-2 Cities, United States, 2012-2014.
AB  - BACKGROUND: Men who have sex with men (MSM) are at risk for cancers attributable
      to human papillomavirus (HPV), including oropharyngeal cancer. Human
      papillomavirus vaccination is recommended for US MSM through age 26 years. Oral
      HPV infection is associated with oropharyngeal cancer. We determined oral HPV
      prevalence and risk factors among young MSM. METHODS: The Young Men's HPV study
      enrolled MSM aged 18 through 26 years from clinics in Chicago and Los Angeles
      during 2012 to 2014. Participants self-reported demographics, sexual behaviors,
      vaccination and human immunodeficiency virus (HIV) status. Self-collected oral
      rinse specimens were tested for HPV DNA (37 types) by L1-consensus PCR. We
      calculated adjusted prevalence ratios (aPR) and 95% confidence intervals (CI) for
      risk factors associated with oral HPV among participants not previously
      vaccinated. RESULTS: Oral HPV was detected in 87 (9.4%) of 922; 9-valent vaccine
      types were detected in 37 (4.0%) of 922. Among HIV-positive participants, 17
      (19.3%) of 88 had oral HPV detected. Oral HPV was more prevalent among those
      reporting first sex at 18 years of age or younger (aPR, 2.44; 95% CI, 1.16-5.12);
      HIV infection (aPR, 1.99; 95% CI, 1.14-3.48); greater than 5 sex partners within
      the past month (aPR, 1.93; 95% CI, 1.13-3.31); performing oral sex on greater
      than 5 partners within the last 3 months (aPR, 1.87; 95% CI, 1.12-3.13); and
      having greater than 5 male sex partners within the last 3 months (aPR, 1.76; 95%
      CI, 1.08-2.87). Only 454 (49.2%) of 922 were aware that HPV can cause
      oropharyngeal cancers. CONCLUSIONS: Many oral HPV infections were with types
      targeted by vaccination. Oral HPV infections were significantly associated with
      HIV and sexual behaviors. Fewer than half of participants were aware that HPV
      could cause oropharyngeal cancer.

PMID- 30204747
TI  - The Surgical Choice of Incidental Periampullary Carcinoma Management in Emergency
      Laparotomy.
AB  - BACKGROUND Laparotomy patients are occasionally diagnosed as having incidental
      periampullary cancers, making emergency pancreaticoduodenectomy (PD) inevitable.
      In this situation is difficult to decide whether to perform an emergency PD or a
      two-stage PD. MATERIAL AND METHODS A total of 27 patients who underwent emergency
      abdominal laparotomy were diagnosed with periampullary or pancreatic cancer
      during the operation without enough preoperative preparation. Ten patients
      underwent emergency one-stage PD and 17 patients underwent two-stage PD. Data of
      137 patients with elective PD were selected as the control group. The
      preoperative, operative, and postoperative parameters, including hospital stay,
      medical cost, blood loss, and postoperative complications between elective PD and
      emergency PD (one-stage and two-stage) and between one-stage PD and two-stage PD
      were analyzed by chi-square test, Fisher test, or t test. RESULTS Patients
      undergoing emergency two-stage PD had less blood loss (P=0.014), while patients
      with one-stage PD had shorter hospital stay (P=0.004), shorter operation time
      (P=0.047), and lower treatment costs (P=0.003). Additionally, the complications
      rates between one-stage and two-stage PD had no significant difference (P=0.365).
      Elective PD was the optimal method due to shorter hospital stay (P<0.001), less
      hemorrhage (P<0.001), shorter operative time (P<0.001), and lower cost (P<0.001)
      compared with emergency PD. CONCLUSIONS Based on our experience, one-stage PD had
      advantages of shorter hospital stay, shorter operation time, and lower treatment
      costs, while two-stage PD had less blood loss. The emergency two-stage PD may be
      more suitable for patients with unstable vital signs if emergency PD is
      inevitable in an emergency laparotomy.

PMID- 30204748
TI  - Survival and development of potato psyllid (Hemiptera: Triozidae) on
      Convolvulaceae: Effects of a plant-fungus symbiosis (Periglandula).
AB  - Plant species in the family Solanaceae are the usual hosts of potato psyllid,
      Bactericera cockerelli (Sulc) (Hemiptera: Psylloidea: Triozidae). However, the
      psyllid has also been shown to develop on some species of Convolvulaceae
      (bindweeds and morning glories). Developmental success on Convolvulaceae is
      surprising given the rarity of psyllid species worldwide associated with this
      plant family. We assayed 14 species of Convolvulaceae across four genera
      (Convolvulus, Calystegia, Ipomoea, Turbina) to identify species that allow
      development of potato psyllid. Two populations of psyllids were assayed (Texas,
      Washington). The Texas population overlaps extensively with native
      Convolvulaceae, whereas Washington State is noticeably lacking in Convolvulaceae.
      Results of assays were overlain on a phylogenetic analysis of plant species to
      examine whether Convolvulaceae distantly related to the typical host (potato)
      were less likely to allow development than species of Convolvulaceae more closely
      related. Survival was independent of psyllid population and location of the plant
      species on our phylogenetic tree. We then examined whether presence of a fungal
      symbiont of Convolvulaceae (Periglandula spp.) affected psyllid survival. These
      fungi associate with Convolvulaceae and produce a class of mycotoxins (ergot
      alkaloids) that may confer protection against plant-feeding arthropods.
      Periglandula was found in 11 of our 14 species, including in two genera
      (Convolvulus, Calystegia) not previously known to host the symbiont. Of these 11
      species, leaf tissues from five contained large quantities of two classes of
      ergot alkaloids (clavines, amides of lysergic acid) when evaluated by LC-MS/MS.
      All five species also harbored Periglandula. No ergot alkaloids were detected in
      species free of the fungal symbiont. Potato psyllid rapidly died on the five
      species that harbored Periglandula and contained ergot alkaloids, but survived to
      adulthood on seven of the nine species in which ergot alkaloids were not
      detected. These results support the hypothesis that a plant-fungus symbiotic
      relationship affects the suitability of certain Convolvulaceae to potato psyllid.

PMID- 30204749
TI  - Evaluating collinearity effects on species distribution models: An approach based
      on virtual species simulation.
AB  - The increasing use of species distribution modeling (SDM) has raised new concerns
      regarding the inaccuracies, misunderstanding, and misuses of this important tool.
      One of those possible pitfalls - collinearity among environmental predictors - is
      assumed as an important source of model uncertainty, although it has not been
      subjected to a detailed evaluation in recent SDM studies. It is expected that
      collinearity will increase uncertainty in model parameters and decrease
      statistical power. Here we use a virtual species approach to compare models built
      using subsets of PCA-derived variables with models based on the original highly
      correlated climate variables. Moreover, we evaluated whether modelling algorithms
      and species data characteristics generate models with varying sensitivity to
      collinearity. As expected, collinearity among predictors decreases the efficiency
      and increases the uncertainty of species distribution models. Nevertheless, the
      intensity of the effect varied according to the algorithm properties: more
      complex procedures behaved better than simple envelope models. This may support
      the claim that complex models such as Maxent take advantage of existing
      collinearity in finding the best set of parameters. The interaction of the
      different factors with species characteristics (centroid and tolerance in
      environmental space) highlighted the importance of the so-called "idiosyncrasy in
      species responses" to model efficiency, but differences in prevalence may
      represent a better explanation. However, even models with low accuracy to predict
      suitability of individual cells may provide meaningful information on the
      estimation of range-size, a key species-trait for macroecological studies. We
      concluded that the use of PCA-derived variables is advised both to control the
      negative effects of collinearity and as a more objective solution for the problem
      of variable selection in studies dealing with large number of species with
      heterogeneous responses to environmental variables.

PMID- 30204751
TI  - Fast and exact search for the partition with minimal information loss.
AB  - In analysis of multi-component complex systems, such as neural systems,
      identifying groups of units that share similar functionality will aid
      understanding of the underlying structures of the system. To find such a
      grouping, it is useful to evaluate to what extent the units of the system are
      separable. Separability or inseparability can be evaluated by quantifying how
      much information would be lost if the system were partitioned into subsystems,
      and the interactions between the subsystems were hypothetically removed. A system
      of two independent subsystems are completely separable without any loss of
      information while a system of strongly interacted subsystems cannot be separated
      without a large loss of information. Among all the possible partitions of a
      system, the partition that minimizes the loss of information, called the Minimum
      Information Partition (MIP), can be considered as the optimal partition for
      characterizing the underlying structures of the system. Although the MIP would
      reveal novel characteristics of the neural system, an exhaustive search for the
      MIP is numerically intractable due to the combinatorial explosion of possible
      partitions. Here, we propose a computationally efficient search to precisely
      identify the MIP among all possible partitions by exploiting the submodularity of
      the measure of information loss, when the measure of information loss is
      submodular. Submodularity is a mathematical property of set functions which is
      analogous to convexity in continuous functions. Mutual information is one such
      submodular information loss function, and is a natural choice for measuring the
      degree of statistical dependence between paired sets of random variables. By
      using mutual information as a loss function, we show that the search for MIP can
      be performed in a practical order of computational time for a reasonably large
      system (N = 100 ~ 1000). We also demonstrate that MIP search allows for the
      detection of underlying global structures in a network of nonlinear oscillators.

PMID- 30204750
TI  - Characterization of neutralizing antibodies reacting with the 213-224 amino-acid
      segment of human galectin-9.
AB  - Extra-cellular galectin-9 (gal-9) is an immuno-modulatory protein with
      predominant immunosuppressive effects. Inappropriate production of gal-9 has been
      reported in several human malignancies and viral diseases like nasopharyngeal,
      pancreatic and renal carcinomas, metastatic melanomas and chronic active viral
      hepatitis. Therefore therapeutic antibodies neutralizing extra-cellular gal-9 are
      expected to contribute to immune restoration in these pathological conditions.
      Two novel monoclonal antibodies targeting gal-9 -Gal-Nab 1 and 2-have been
      produced and characterized in this study. We report a protective effect of Gal
      Nab1 and Gal-Nab2 on the apoptotic cell death induced by gal-9 in primary T
      cells. In addition, they inhibit late phenotypic changes observed in peripheral T
      cells that survive gal-9-induced apoptosis. Gal-Nab1 and Gal-Nab2 bind nearly
      identical, overlapping linear epitopes contained in the 213-224 amino-acid
      segments of gal-9. Nevertheless, they have some distinct functional
      characteristics suggesting that their three-dimensional epitopes are distinct.
      These differences are best demonstrated when gal-9 is applied on Jurkat cells
      where Gal-Nab1 is less efficient than Gal-Nab2 in the prevention of apoptotic
      cell death. In addition, Gal-Nab1 stimulates non-lethal phosphatidylserine
      translocation at the plasma membrane and calcium mobilization triggered by gal-9
      in these cells. Both Gal-Nab1 and 2 cross-react with murine gal-9. They bind its
      natural as well as its recombinant form. This cross-species recognition will be
      an advantage for their assessment in pre-clinical tumor models.

PMID- 30204752
TI  - Mother's knowledge on prevention of mother-to-child transmission of HIV,
      Ethiopia: A cross sectional study.
AB  - OBJECTIVE: To identify proportion of and factors for comprehensive knowledge on
      prevention of mother-to-child transmission of HIV in pregnant women attending
      antenatal care in Northern Ethiopia. METHODS: A total of 416 pregnant women were
      interviewed between October 2012 and May 2013. Logistic regression analysis was
      used to identify factors for comprehensive knowledge on prevention of mother-to
      child transmission of HIV. RESULTS: The proportion of pregnant women, who have
      comprehensive knowledge on prevention of mother-to-child transmission of HIV, was
      52%. The odds of having comprehensive knowledge on prevention of mother-to-child
      transmission of HIV were higher among pregnant women who were younger (16 to 24
      years old) (Adjusted Odds Ratio (AOR) = 2.95; 95%CI: 1.20, 7.26), urban residents
      (AOR = 2.45; 95%CI: 1.39, 4.32), attending secondary education and above (AOR =
      4.43; 95%CI: 2.40, 8.20), employed (AOR = 4.99;95%CI: 2.45, 10.16), have five
      children or more (AOR = 9.34; 95%CI:3.78, 23.07), have favored attitude towards
      HIV positive living (AOR = 2.53; 95%CI: 1.43, 4.44) and have perceived
      susceptibility to HIV (AOR = 10.72; 95%CI: 3.90, 29.39). CONCLUSION: The
      proportion of women who have comprehensive knowledge on prevention of mother-to
      child transmission of HIV in this study setting was low. Measures which will
      escalate mother's knowledge on prevention of mother-to-child transmission of HIV
      should be emphasized. Efforts to improve mother's knowledge on prevention of
      mother-to-child transmission of HIV should target women who were older age (> =
      35years), rural residents, unemployed, not attending formal education,
      primigravids, have no favored attitude towards HIV positive living and have not
      perceived susceptibility to HIV.

PMID- 30204753
TI  - Precise time-matching in chimpanzee allogrooming does not occur after a short
      delay.
AB  - Allogrooming is a key aspect of chimpanzee sociality and many studies have
      investigated the role of reciprocity in a biological market. One theoretical form
      of reciprocity is time-matching, where payback consists of an equal duration of
      effort (e.g. twenty seconds of grooming repaid with twenty seconds of grooming).
      Here, we report a study of allogrooming in a group of twenty-six captive
      chimpanzees (Chester Zoo, UK), based on more than 150 hours of data. For
      analysis, we introduce a methodological innovation called the "Delta scale",
      which unidimensionally measures the accuracy of time-matching according to the
      extent of delay after the cessation of grooming. Delta is positive when
      reciprocation occurs after any non-zero delay (e.g. A grooms B and then B grooms
      A after a five second break) and it is negative when reciprocation begins whilst
      the original grooming has not yet ceased. Using a generalized linear mixed
      method, we found evidence for time-matched reciprocation. However, this was true
      only for immediate reciprocation (Delta less than zero). If there was a temporal
      break in grooming between two members of a dyad, then there was no evidence that
      chimpanzees were using new bouts to retroactively correct for time-matching
      imbalances from previous bouts. Our results have implications for some of the
      cognitive constraints that differentiate real-life reciprocation from abstract
      theoretical models. Furthermore, we suggest that some apparent patterns of time
      matched reciprocity may arise merely due to the law of large numbers, and we
      introduce a statistical test which takes this into account when aggregating
      grooming durations over a window of time.

PMID- 30204755
TI  - Associations of device-measured physical activity across adolescence with
      metabolic traits: Prospective cohort study.
AB  - BACKGROUND: Multiple occasions of device-measured physical activity have not been
      previously examined in relation to metabolic traits. We described associations of
      total activity, moderate-to-vigorous physical activity (MVPA), and sedentary time
      from three accelerometry measures taken across adolescence with detailed traits
      related to systemic metabolism. METHODS AND FINDINGS: There were 1,826 male and
      female participants recruited at birth in 1991-1992 via mothers into the Avon
      Longitudinal Study of Parents and Children offspring cohort who attended clinics
      in 2003-2005, 2005-2006, and 2006-2008 who were included in >=1 analysis. Waist
      worn uniaxial accelerometers measured total activity (counts/min), MVPA (min/d),
      and sedentary time (min/d) over >=3 d at mean age 12y, 14y, and 15y. Current
      activity (at age 15y), mean activity across occasions, interaction by previous
      activity, and change in activity were examined in relation to systolic and
      diastolic blood pressure, insulin, C-reactive protein, and 230 traits from
      targeted metabolomics (nuclear magnetic resonance spectroscopy), including
      lipoprotein cholesterol and triglycerides, amino and fatty acids, glycoprotein
      acetyls, and others, at age 15y. Mean current total activity was 477.5 counts/min
      (SD = 164.0) while mean MVPA and sedentary time durations were 23.6 min/d (SD =
      17.9) and 522.1 min/d (SD = 66.0), respectively. Mean body mass index at age 15y
      was 21.4 kg/m2 (SD = 3.5). Correlations between first and last activity
      measurement occasions were low (e.g., r = 0.40 for counts/min). Current activity
      was most strongly associated with cholesterol and triglycerides in high-density
      lipoprotein (HDL) and very low-density lipoprotein (VLDL) particles (e.g., -0.002
      mmol/l or -0.18 SD units; 95% CI -0.24--0.11 for triglycerides in chylomicrons
      and extremely large very low-density lipoprotein [XL VLDL]) and with glycoprotein
      acetyls (-0.02 mmol/l or -0.16 SD units; 95% CI -0.22--0.10), among others.
      Associations were similar for mean activity across 3 occasions. Attenuations were
      modest with adjustment for fat mass index based on dual-energy X-ray
      absorptiometry (DXA). In mutually adjusted models, higher MVPA and sedentary time
      were oppositely associated with cholesterol and triglycerides in VLDL and HDL
      particles (MVPA more strongly with glycoprotein acetyls and sedentary time more
      strongly with amino acids). Associations appeared less consistent for sedentary
      time than for MVPA based on longer-term measures and were weak for change in all
      activity types from age 12y-15y. Evidence was also weak for interaction between
      activity types at age 15y and previous activity measures in relation to most
      traits (minimum P = 0.003; median P = 0.26 for counts/min) with interaction
      coefficients mostly positive. Study limitations include modest sample sizes and
      relatively short durations of accelerometry measurement on each occasion (3-7 d)
      and of time lengths between first and last accelerometry occasions (<4 years),
      which can obscure patterns from chance variation and limit description of
      activity trajectories. Activity was also recorded using uniaxial accelerometers
      which predated more sensitive triaxial devices. CONCLUSIONS: Our results support
      associations of physical activity with metabolic traits that are small in
      magnitude and more robust for higher MVPA than lower sedentary time. Activity
      fluctuates over time, but associations of current activity with most metabolic
      traits do not differ by previous activity. This suggests that the metabolic
      effects of physical activity, if causal, depend on most recent engagement.

PMID- 30204756
TI  - Genomic region detection via Spatial Convex Clustering.
AB  - Several modern genomic technologies, such as DNA-Methylation arrays, measure
      spatially registered probes that number in the hundreds of thousands across
      multiple chromosomes. The measured probes are by themselves less interesting
      scientifically; instead scientists seek to discover biologically interpretable
      genomic regions comprised of contiguous groups of probes which may act as
      biomarkers of disease or serve as a dimension-reducing pre-processing step for
      downstream analyses. In this paper, we introduce an unsupervised feature learning
      technique which maps technological units (probes) to biological units (genomic
      regions) that are common across all subjects. We use ideas from fusion penalties
      and convex clustering to introduce a method for Spatial Convex Clustering, or
      SpaCC. Our method is specifically tailored to detecting multi-subject regions of
      methylation, but we also test our approach on the well-studied problem of
      detecting segments of copy number variation. We formulate our method as a convex
      optimization problem, develop a massively parallelizable algorithm to find its
      solution, and introduce automated approaches for handling missing values and
      determining tuning parameters. Through simulation studies based on real
      methylation and copy number variation data, we show that SpaCC exhibits
      significant performance gains relative to existing methods. Finally, we
      illustrate SpaCC's advantages as a pre-processing technique that reduces large
      scale genomics data into a smaller number of genomic regions through several
      cancer epigenetics case studies on subtype discovery, network estimation, and
      epigenetic-wide association.

PMID- 30204757
TI  - The vacuolar-type ATPase inhibitor archazolid increases tumor cell adhesion to
      endothelial cells by accumulating extracellular collagen.
AB  - The vacuolar-type H+-ATPase (v-ATPase) is the major proton pump that acidifies
      intracellular compartments of eukaryotic cells. Since the inhibition of v-ATPase
      resulted in anti-tumor and anti-metastatic effects in different tumor models,
      this enzyme has emerged as promising strategy against cancer. Here, we used the
      well-established v-ATPase inhibitor archazolid, a natural product first isolated
      from the myxobacterium Archangium gephyra, to study the consequences of v-ATPase
      inhibition in endothelial cells (ECs), in particular on the interaction between
      ECs and cancer cells, which has been neglected so far. Human endothelial cells
      treated with archazolid showed an increased adhesion of tumor cells, whereas the
      transendothelial migration of tumor cells was reduced. The adhesion process was
      independent from the EC adhesion molecules ICAM-1, VCAM-1, E-selectin and N
      cadherin. Instead, the adhesion was mediated by beta1-integrins expressed on
      tumor cells, as blocking of the integrin beta1 subunit reversed this process.
      Tumor cells preferentially adhered to the beta1-integrin ligand collagen and
      archazolid led to an increase in the amount of collagen on the surface of ECs.
      The accumulation of collagen was accompanied by a strong decrease of the
      expression and activity of the protease cathepsin B. Overexpression of cathepsin
      B in ECs prevented the capability of archazolid to increase the adhesion of tumor
      cells onto ECs. Our study demonstrates that the inhibition of v-ATPase by
      archazolid induces a pro-adhesive phenotype in endothelial cells that promotes
      their interaction with cancer cells, whereas the transmigration of tumor cells
      was reduced. These findings further support archazolid as a promising anti
      metastatic compound.

PMID- 30204758
TI  - The prevalence of adverse postnatal outcomes for mother and infant in the
      Netherlands.
AB  - BACKGROUND: In high-income countries delivery usually takes place in a short-stay
      hospital setting and includes limited specific care after discharge. Perinatal
      system performance is therefore predominantly expressed in direct terms of
      delivery outcomes such as preterm birth (PTB), small for gestational age (SGA)
      or, in case of the mother, perineal rupture and haemorrhage. Additional postnatal
      complications may emerge, but their incidence is largely unknown. The Dutch
      obstetric system includes an 8-10 day episode of professional postnatal home
      maternity care. Our aim was to establish, under routine conditions, the incidence
      of a comprehensive set of 67 predefined complications and their predictors. A
      second aim was to address interaction between maternal and child complications.
      METHODS: The study design was a prospective cohort study of all clients of one
      large maternity care organization receiving home maternity care in November 2014.
      We combined maternal background and intrapartum and postnatal characteristics
      with complication data, routinely recorded by home maternity care assistants.
      Complication prevalence rates per postnatal day were calculated. Univariate and
      multivariable logistic regression were used to predict the presence of postnatal
      complications. RESULTS: Complications occurred throughout the entire episode of
      home maternity care and prevalence was high, with 55% of all mother-baby pairs
      experiencing at least one complication (e.g. cracked nipples, >10% weight loss of
      the baby) and 5% at least one major complication (e.g. mastitis, cyanosis of the
      baby). Predictive ability of maternal background and intrapartum and postnatal
      variables on presence of complications was moderate (max. 62.9%), even when a
      cumulative risk score was used. CONCLUSIONS: The prevalence rates of maternal and
      neonatal postnatal complications with care as usual in high-income countries was
      higher than expected. Professional postnatal follow-up is to be considered in
      order to timely detect and manage emerging complications with minimal delay.
      Opportunities for risk-guided care should be investigated further. The pattern of
      complications in low-income countries remains to be established.

PMID- 30204754
TI  - Tick-borne zoonoses in the Order Rickettsiales and Legionellales in Iran: A
      systematic review.
AB  - BACKGROUND: Tick-borne zoonoses in the Order Rickettsiales and Legionellales
      cause infections that often manifest as undifferentiated fevers that are not easy
      to distinguish from other causes of acute febrile illnesses clinically. This is
      partly attributed to difficulty in laboratory confirmation since convalescent
      sera, specific diagnostic reagents, and the required expertise may not be readily
      available. As a result, a number of tick-borne zoonoses are underappreciated
      resulting in unnecessary morbidity, mortality and huge economic loses. In Iran, a
      significant proportion of human infectious diseases are tick-borne, with
      anecdotal evidence suggesting that tick-borne zoonoses are widespread but
      underreported in the country. Epidemiological review is therefore necessary to
      aid in the effective control and prevention of tick-borne zonooses in Iran. The
      aim of this review is to provide an in-depth and comprehensive overview of
      anaplasmosis, ehrlichiosis, spotted fever group rickettsioses and coxiellosis in
      Iran. METHODS: Using the Preferred Reporting Items for Systematic Reviews and
      Meta-Analyses (PRISMA) guidelines, all relevant publications on tick-borne
      zoonoses in the Order Rickettsiales and Legionellales in Iran were searched using
      a number of search terms. The search was confined to authentic resources from
      repositories of popular data bases among them PubMed, Web of Science, Google
      Scholar, Science Direct, SpringerLink and SCOPUS. The search items included peer
      reviewed journals, books and book chapters published between 1996 and 2017.
      RESULTS: A total of 1 205 scientific publications and reports were sourced, of
      which 63 met the search criteria and were reviewed. Of the 63 articles reviewed,
      36 (57.1%) reported on coxiellosis, 15 (23.8%) on anaplasmosis, 11 (17.5%) on
      ehrlichiosis and 1(1.6%) on spotted fever group rickettsiae in a large scale
      study involving four countries, among them Iran. The existence of tick-borne
      pathogens in the Order Rickettsiales and Legionellales was confirmed by
      molecular, serological and microscopic techniques conducted on samples obtained
      from sheep, cattle, goats, camels, poultry, animal products (milk and eggs),
      dogs, ticks and even human subjects in different parts of the country; pointing
      to a countrywide distribution. DISCUSSION: Based on the review, coxiellosis,
      anaplasmosis, ehrlichiosis, and SFG rickettsiae can be categorized as emerging
      tick-borne zoonotic diseases in Iran given the presence of their causiative
      agents (C. burnetii, A. phagocytophilum, A. marginale, A. bovis, A. ovis, A.
      central, E. canis, E. ewingii, E. chaffeensis and R. conorii) collectively
      reported in a variety of domestic animals, animal products, arthropods and human
      beings drawn from 22 provinces in Iran. CONCLUSION: Given the asymptomatic nature
      of some of these zoonoses, there is a high likelihood of silent transmission to
      humans in many parts of the country, which should be considered a public health
      concern. Presently, information on the transmission intensity of tick-borne
      zoonoses caused by pathogens in the Order Rickettsiales and Legionellales to
      humans and its public health impact in Iran is scanty.

PMID- 30204760
TI  - Assessing methodological quality of Russian clinical practice guidelines and
      introducing AGREE II instrument in Russia.
AB  - BACKGROUND: There are multiple organisations in Russia that publish clinical
      practice guidelines (CPGs). The demand for CPGs and appreciation of their role in
      healthcare provision has been steadily growing. However, quality and methodology
      of development of CPGs have not been systematically addressed. AIM: To analyse
      the quality of Russian-produced CPGs for surgical treatment of hepatic-pancreatic
      biliary diseases. METHODS: We searched Russian databases for CPGs, published
      between 2013 and 2017. We identified 6 relevant documents that met our inclusion
      criteria. We approached four experts in the field with written and verbal
      instructions on the use of the AGREE II questionnaire. RESULTS: All six CPGs
      received the highest domain scores for the domain Clarity of Presentation (46%
      80%). The lowest domain scores were for the domain Editorial Independence (6%
      25%). Overall, the experts put the highest total sum scores to the CPG for
      treating chronic pancreatitis (70%), while the lowest total sum score was
      attributed to the CPG for treating acute cholangitis (22%). CONCLUSIONS: The
      overall quality of CPGs, as assessed by the four experts with the AGREE II
      instrument, was low. The highest scoring, best organized and most comprehensive
      and straightforward CPG was the one for chronic pancreatitis. The AGREE II
      instrument should be considered for use in Russia by guideline developers to
      assess existing CPGs and inform the creation of new guidelines.

PMID- 30204759
TI  - Oxidative stress in healthy pregnancy and preeclampsia is linked to chronic
      inflammation, iron status and vascular function.
AB  - BACKGROUND: During normal pregnancy, placental oxidative stress (OS) is present
      during all three trimesters and is necessary to obtain normal cell function.
      However, if OS reaches a certain level, pregnancy complications might arise. In
      preeclampsia (PE), a dangerous pregnancy specific hypertensive disorder, OS
      induced in the ischemic placenta causes a systemic inflammatory response and
      activates maternal endothelial cells. In this study, we aimed to quantify
      superoxide concentrations (as a measure of systemic OS) using electron
      paramagnetic resonance (EPR) and correlate them to markers of systemic
      inflammation, iron status and vascular function. METHODS: Fifty-nine women with a
      healthy pregnancy (HP), 10 non-pregnant controls (NP) and 28 PE patients (32+/
      3.3weeks) were included. During HP, blood samples for superoxide, neutrophil to
      lymphocyte ratio (NLR), mean platelet volume (MPV) and iron status were taken at
      10, 25 and 39 weeks. Vascular measurements for arterial stiffness (carotid
      femoral pulse wave velocity (CF-PWV), augmentation index (AIx), augmentation
      Pressure (AP)) and microvascular endothelial function (reactive hyperemia index
      (RHI)) were performed at 35 weeks. In PE, all measurements were performed at
      diagnosis. CMH (1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine) was
      used as spin probe for EPR, since the formed CM radical corresponds to the amount
      of superoxide. RESULTS: Superoxide concentration remains stable during pregnancy
      (p = 0.92), but is significantly higher compared to the NP controls (p<0.0001).
      At 25 weeks, there is a significant positive correlation between superoxide and
      ferritin concentration. (p = 0.04) In PE, superoxide, systemic inflammation and
      iron status are much higher compared to HP (all p<0.001). During HP, superoxide
      concentrations correlate significantly with arterial stiffness (all p<0.04),
      while in PE superoxide is significantly correlated to microvascular endothelial
      function (p = 0.03). CONCLUSIONS: During HP there is an increased but stable
      oxidative environment, which is correlated to ferritin concentration. If
      superoxide levels increase, there is an augmentation in arterial stiffness. In PE
      pregnancies, systemic inflammation and superoxide concentrations are higher and
      result in a deterioration of endothelial function. Together, these findings
      support the hypothesis that vascular function is directly linked to the amount of
      OS and that measurement of OS in combination with vascular function tests might
      be used in the prediction of PE.

PMID- 30204761
TI  - Factors associated with program effectiveness in the implementation of a sexual
      risk reduction intervention for female sex workers across Mexico: Results from a
      randomized trial.
AB  - OBJECTIVE: The overall aim of this paper is to examine effectiveness of an
      evidence-based intervention in community settings, and the factors associated
      with effectiveness. Limited research in the area of HIV prevention has focused on
      evaluating intervention program effectiveness in real-world settings. METHODS: We
      implemented an efficacious theory-based sexual risk reduction intervention for
      female sex workers (FSW) called Mujer Segura across 13 different clinics in 13
      sites across Mexico. The overall design was a cluster randomized Type I design
      simultaneously testing intervention program effectiveness with an observational
      study of implementation factors. We aimed to examine the effectiveness of Mujer
      Segura at reducing HIV/STI incidence among FSW participants at each site, and to
      examine the client-, provider-, organization-, and structure-related factors
      associated with program effectiveness. RESULTS: We found lower HIV/STI incidence
      density in the intervention relative to the control group in 5 sites we labeled
      as "program effective sites," but not in 8 sites we labeled as "program
      ineffective sites." Using generalized estimating equations controlling for site
      and computed mean difference effect sizes, we examined statistically and
      practically significant differences, respectively, between the two groups of
      sites along various client-, provider-, organization-, and structure-related
      characteristics. Results indicated that client-level HIV/AIDS related knowledge,
      and proficiency and engagement in the organizational social context were
      associated with program effectiveness. CONCLUSIONS: Enormous resources are
      required to systematically and adequately test the role of multilevel factors on
      program effectiveness. We successfully implemented Mujer Segura in 13 sites in
      Mexico. Results suggest that other measures may need to be included in future
      implementation studies than the ones included here. We were able to point to a
      few specific factors that should be targeted to increase effectiveness of similar
      evidence-based programs in low- and other middle-income countries like Mexico.
      TRIAL REGISTRATION: ClinicalTrials.gov NCT01465607.

PMID- 30204762
TI  - Two-level resolution of relative risk of dengue disease in a hyperendemic city of
      Colombia.
AB  - Risk maps of dengue disease offer to the public health officers a tool to model
      disease risk in space and time. We analyzed the geographical distribution of
      relative incidence risk of dengue disease in a high incidence city from Colombia,
      and its evolution in time during the period January 2009-December 2015,
      identifying regional effects at different levels of spatial aggregations. Cases
      of dengue disease were geocoded and spatially allocated to census sectors, and
      temporally aggregated by epidemiological periods. The census sectors are nested
      in administrative divisions defined as communes, configuring two levels of
      spatial aggregation for the dengue cases. Spatio-temporal models including census
      sector and commune-level spatially structured random effects were fitted to
      estimate dengue incidence relative risks using the integrated nested Laplace
      approximation (INLA) technique. The final selected model included two-level
      spatial random effects, a global structured temporal random effect, and a census
      sector-level interaction term. Risk maps by epidemiological period and risk
      profiles by census sector were generated from the modeling process, showing the
      transmission dynamics of the disease. All the census sectors in the city
      displayed high risk at some epidemiological period in the outbreak periods.
      Relative risk estimation of dengue disease using INLA offered a quick and
      powerful method for parameter estimation and inference.

PMID- 30204763
TI  - Predictors of noncompliance to pulmonary tuberculosis treatment: An insight from
      South America.
AB  - PURPOSE: To investigate the factors associated with a higher risk of
      noncompliance to tuberculosis (TB) treatment in Porto Alegre, Brazil. METHODS: We
      identified 478 adult patients for this case-control study undergoing treatment
      for confirmed pulmonary TB. Cases (noncompliance) were defined as patients who
      stopped treatment for more than 30 consecutive days (n = 118). Controls were
      defined as all patients who completed treatment and were cured (n = 360). Factors
      associated with noncompliance were calculated with unadjusted and adjusted odds
      ratio (OR). RESULTS: The rate of noncompliance in our study was 25%. The factors
      of noncompliance after adjustments in the overall population were, in order of
      magnitude, living in an area of lower income (OR = 4.35, 95%CI: 2.50-7.58), abuse
      of drugs (OR = 2.73, 95%CI: 1.47-5.09), nonadherence to a previous treatment
      regimen (OR = 2.1, 95%CI: 1.28-3.45), and history of smoking (OR = 1.72, 95%CI:
      1.00-3.00). Age, race, gender, level of education, HIV infection or diabetes
      status were not associated with a higher risk of noncompliance. In the subgroup
      of re-treatment cases, poverty (OR = 2.65; 95%CI = 1.06-6.66), smoking history
      (OR = 2.94; 95%CI = 1.09-7.92), male gender (OR = 3.25; 95%CI = 1.32-8.0), and
      younger age (OR = 4.3; 95%CI = 1.15-16.07) were also associated with a higher
      risk of dropout. CONCLUSION: Predictors of poor compliance to TB treatment were
      low income, abuse of drugs, re-treatment cases and history of smoking.

PMID- 30204764
TI  - Using tagging data and aerial surveys to incorporate availability bias in the
      abundance estimation of blue sharks (Prionace glauca).
AB  - There is worldwide concern about the status of elasmobranchs, primarily as a
      result of overfishing and bycatch with subsequent ecosystem effects following the
      removal of top predators. Whilst abundant and wide-ranging, blue sharks (Prionace
      glauca) are the most heavily exploited shark species having suffered marked
      declines over the past decades, and there is a call for robust abundance
      estimates. In this study, we utilized depth data collected from two blue sharks
      using pop-up satellite archival tags, and modelled the proportion of time the
      sharks were swimming in the top 1-meter layer and could therefore be detected by
      observers conducting aerial surveys. The availability models indicated that the
      tagged sharks preferred surface waters whilst swimming over the continental shelf
      and during daytime, with a model-predicted average proportion of time spent at
      the surface of 0.633 (SD = 0.094) for on-shelf, and 0.136 (SD = 0.075) for off
      shelf. These predicted values were then used to account for availability bias in
      abundance estimates for the species over a large area in the Northeast Atlantic,
      derived through distance sampling using aerial survey data collected in 2015 and
      2016 and modelled with density surface models. Further, we compared abundance
      estimates corrected with model-predicted availability to uncorrected estimates
      and to estimates that incorporated the average time the sharks were available for
      detection. The mean abundance (number of individuals) corrected with modelled
      availability was 15,320 (CV = 0.28) in 2015 and 11,001 (CV = 0.27) in 2016.
      Depending on the year, these estimates were ~7 times higher compared to estimates
      without the bias correction, and ~3 times higher compared to the abundances
      corrected with average availability. When the survey area contains habitat
      heterogeneity that may affect surfacing patterns of animals, modelling animals'
      availability provides a robust alternative to correcting for availability bias
      and highlights the need for caution when applying "average" correction factors.

PMID- 30204765
TI  - A Markov chain for numerical chromosomal instability in clonally expanding
      populations.
AB  - Cancer cells frequently undergo chromosome missegregation events during mitosis,
      whereby the copies of a given chromosome are not distributed evenly among the two
      daughter cells, thus creating cells with heterogeneous karyotypes. A stochastic
      model tracing cellular karyotypes derived from clonal populations over hundreds
      of generations was recently developed and experimentally validated, and it was
      capable of predicting favorable karyotypes frequently observed in cancer. Here,
      we construct and study a Markov chain that precisely describes karyotypic
      evolution during clonally expanding cancer cell populations. The Markov chain
      allows us to directly predict the distribution of karyotypes and the expected
      size of the tumor after many cell divisions without resorting to computationally
      expensive simulations. We determine the limiting karyotype distribution of an
      evolving tumor population, and quantify its dependency on several key parameters
      including the initial karyotype of the founder cell, the rate of whole chromosome
      missegregation, and chromosome-specific cell viability. Using this model, we
      confirm the existence of an optimal rate of chromosome missegregation
      probabilities that maximizes karyotypic heterogeneity, while minimizing the
      occurrence of nullisomy. Interestingly, karyotypic heterogeneity is significantly
      more dependent on chromosome missegregation probabilities rather than the number
      of cell divisions, so that maximal heterogeneity can be reached rapidly (within a
      few hundred generations of cell division) at chromosome missegregation rates
      commonly observed in cancer cell lines. Conversely, at low missegregation rates,
      heterogeneity is constrained even after thousands of cell division events. This
      leads us to conclude that chromosome copy number heterogeneity is primarily
      constrained by chromosome missegregation rates and the risk for nullisomy and
      less so by the age of the tumor. This model enables direct integration of
      karyotype information into existing models of tumor evolution based on somatic
      mutations.

PMID- 30204766
TI  - Off-label use of ceftiofur in one-day chicks triggers a short-term increase of
      ESBL-producing E. coli in the gut.
AB  - This trial was designed to evaluate the off-label use of ceftiofur with Marek's
      vaccine in one-day-old broiler chicks, a prophylactic treatment that has been
      done in some commercial hatcheries, on the emergence of extended-spectrum beta
      lactamase producing Escherichia coli (ESBL-E. coli). A total of 168 chicks
      (Cobb500(r)) were used in a completely randomized design. Birds were assigned to
      two treatments (Marek's vaccine plus saline vs Marek's vaccine plus ceftiofur)
      and six repetitions, with 14 animals each. Cloacal swabs were collected from 1 to
      14 days post-hatch. The majority (86%; p<0.0001) of the ESBL-producing isolates
      harboring blaCTX-M and blaSHV genes originated from animals receiving the
      antimicrobial. None of the isolates were positive for plasmid-mediated AmpC
      betalactamase genes (blaACC, blaCMY-2, blaDHA, blaFOX, blaMOX and blaMIR). These
      findings indicate that the off-label use of ceftiofur with Marek's vaccine is
      associated with the short-term increase in ESBL-producing Escherichia coli in the
      gut of chicks.

PMID- 30204767
TI  - Metagenomics reveals niche partitioning within the phototrophic zone of a
      microbial mat.
AB  - Hypersaline photosynthetic microbial mats are stratified microbial communities
      known for their taxonomic and metabolic diversity and strong light-driven day
      night environmental gradients. In this study of the upper photosynthetic zone of
      hypersaline microbial mats of Elkhorn Slough, California (USA), we show how
      metagenome sequencing can be used to meaningfully assess microbial ecology and
      genetic partitioning in these complex microbial systems. Mapping of metagenome
      reads to the dominant Cyanobacteria observed in the system, Coleofasciculus
      (Microcoleus) chthonoplastes, was used to examine strain variants within these
      metagenomes. Highly conserved gene subsystems indicated a core genome for the
      species, and a number of variant genes and subsystems suggested strain level
      differentiation, especially for nutrient utilization and stress response.
      Metagenome sequence coverage binning was used to assess ecosystem partitioning of
      remaining microbes to both reconstruct the model organisms in silico and identify
      their ecosystem functions as well as to identify novel clades and propose their
      role in the biogeochemical cycling of mats. Functional gene annotation of these
      bins (primarily of Proteobacteria, Bacteroidetes, and Cyanobacteria)
      recapitulated the known biogeochemical functions in microbial mats using a
      genetic basis, and revealed significant diversity in the Bacteroidetes,
      presumably in heterotrophic cycling. This analysis also revealed evidence of
      putative phototrophs within the Gemmatimonadetes and Gammaproteobacteria residing
      in microbial mats. This study shows that metagenomic analysis can produce
      insights into the systems biology of microbial ecosystems from a genetic
      perspective and to suggest further studies of novel microbes.

PMID- 30204768
TI  - Comparative effectiveness of antihypertensive drugs prescribed in Ethiopian
      healthcare practice: A pilot prospective, randomized, open label study.
AB  - BACKGROUND: Previous research has been highly suggestive that patients of African
      ancestry are less responsive to beta-blockers and angiotensin converting enzyme
      inhibitors. However, clinical practice within Ethiopia has continued to recommend
      all drugs for treatment of hypertension despite the lack of evidentiary support.
      Therefore this study aims to compare the effectiveness of the three major
      antihypertensive drugs currently prescribed in an Ethiopian health care setting
      to further the potential for evidence based prescribing practices. METHODS: A
      prospective, randomized, open label comparative study was used to determine the
      mean reduction in blood pressure (primary outcome) and assess cardiovascular
      events (secondary outcomes) among patients receiving one or more of three common
      antihypertensive drugs (i.e., nifedipine, hydrochlorothiazide, and enalapril) in
      routine clinical practice between November 2016 and April 2017. Patients were
      followed for three months. Analysis was based on an intention-to-treat approach.
      One way analysis of covariance was used to compare the difference in therapeutic
      effectiveness in reducing blood pressure. RESULT: A total of 141 patients were
      randomized to one of three recipient groups-nifedipine (n = 47), enalapril (n =
      47) or hydrochlorothiazide (n = 47). Three months after randomization, 44
      patients in each group completed the follow-up. Patients randomized to nifedipine
      had significantly higher mean reduction in systolic blood pressure than those
      randomized to enalapril(p = 0.003) or hydrochlorothiazide(p = 0.036). The mean
      reduction in systolic blood pressure was -37.35(CI:-40, -34.2) in the nifedipine
      group; -30.3(CI: -33.5, -27.1) in patients receiving enalapril; and -32.1(CI:-35,
      -29.3) in patients assigned hydrochlorothiazide. However, nifedipine did not have
      a significance difference in reduction of mean diastolic blood pressure compared
      than those receiving enalapril (p = 0.57) or hydrochlorthiazide (p = 0.99).
      CONCLUSION: This study revealed that amongst the three drugs nifedipine was found
      to be the most effective drug in reduction of systolic blood pressure.
      Hydrochlorothiazide and enalapril did not show a difference in reduction of mean
      blood pressure. Further, long term randomized trials are highly recommended to
      inform revision of Ethiopia-centric hypertension treatment guidelines.

PMID- 30204769
TI  - Functional shortcuts in language co-occurrence networks.
AB  - Human language contains regular syntactic structures and grammatical patterns
      that should be detectable in their co-occurence networks. However, most standard
      complex network measures can hardly differentiate between co-occurence networks
      built from an empirical corpus and a body of scrambled text. In this work, we
      employ a motif extraction procedure to show that empirical networks have much
      greater motif densities. We demonstrate that motifs function as efficient and
      effective shortcuts in language networks, potentially explaining why we are able
      to generate and decipher language expressions so rapidly. Finally we suggest a
      link between motifs and constructions in Construction Grammar as well as
      speculate on the mechanisms behind the emergence of constructions in the early
      stages of language acquisition.

PMID- 30204770
TI  - Filamentation and restoration of normal growth in Escherichia coli using a
      combined CRISPRi sgRNA/antisense RNA approach.
AB  - CRISPR interference (CRISPRi) using dCas9-sgRNA is a powerful tool for the
      exploration and manipulation of gene functions. Here we quantify the reversible
      switching of a central process of the bacterial cell cycle by CRISPRi and an
      antisense RNA mechanism. Reversible induction of filamentous growth in E. coli
      has been recently demonstrated by controlling the expression levels of the
      bacterial cell division proteins FtsZ/FtsA via CRISPRi. If FtsZ falls below a
      critical level, cells cannot divide. However, the cells remain metabolically
      active and continue with DNA replication. We surmised that this makes them
      amenable to an inducible antisense RNA strategy to counteract FtsZ inhibition. We
      show that both static and inducible thresholds can adjust the characteristics of
      the switching process. Combining bulk data with single cell measurements, we
      characterize the efficiency of the switching process. Successful restoration of
      division is found to occur faster in the presence of antisense sgRNAs than upon
      simple termination of CRISPRi induction.

PMID- 30204771
TI  - Dicomflex: A novel framework for efficient deployment of image analysis tools in
      radiological research.
AB  - OBJECTIVE: Medical image processing tools in research are often developed from
      scratch without the use of predefined software structures, which potentially
      makes them less reliable and difficult to maintain. The objective here was to
      present and evaluate a novel framework (Dicomflex) for the deployment of tools
      with a uniform workflow, commonly encountered in medical image analysis.
      MATERIALS AND METHODS: The object-oriented code was developed using Matlab.
      Dicomflex applications follow the common workflow of image-slice selection, user
      interaction, image processing, result visualization and progression to next
      slice. The framework consists of three important classes that host functionality,
      two configuration files and a front end that displays images, graphs and
      resulting data. RESULTS: So far, three different research tools have been created
      under the new framework. In comparison with previous Matlab analysis tools used
      at our institution, users of Dicomflex tools subjectively considered the learning
      phase to be shorter and handling to be simpler and more intuitive. They also
      highlighted the benefit and comfort of the standardized interface and predefined
      workflow. The framework-inherent handling of software versions was considered
      highly beneficial for maintenance as well as data and software management at
      different project stages. The clear separation of framework-related and unrelated
      code allows for a fast and more direct design of new tools in well-defined steps.
      The flexibility of the framework translates to a wide range of image processing
      tasks, such as segmentation, region-of-interest (ROI) analyses or computation of
      functional parameter maps, but is limited to 2D datasets. CONCLUSION: Potential
      medical applications include the assessment of cardiac performance, detection of
      cerebrovascular disease or characterization of cancerous lesions. Dicomflex tools
      share a similar workflow and host the pertinent functions only. This may be
      relevant for many image processing needs in radiological research, where quick
      software deployment and reliability of results is essential.

PMID- 30204772
TI  - Association between adaptive immunity and neutrophil dynamics in zebrafish (Danio
      rerio) infected by a parasitic ciliate.
AB  - The protective immune response in zebrafish (Danio rerio) against the parasitic
      ciliate Ichthyophthirius multifiliis, targeting host skin, fins and gills,
      comprises an accelerated and manifold elevated immunoglobulin gene expression as
      well as a significantly elevated number of neutrophils at infected sites.
      Experimental fish were subjected to a primary I. multifiliis infection followed
      by a series of secondary exposures before they were challenged by a high dosage
      of infective theronts. Immunized fish responded immediately with a protective
      response suggesting existence of immunological memory whereas fish exposed to the
      parasite for the first time obtained a marked infection. The primary response to
      infection was dominated by expression of genes encoding acute phase reactants and
      inflammatory cytokines as well as recruitment of neutrophils at infected
      locations. Immunized fish showed a significantly upregulated immunoglobulin gene
      expression following challenge, which indicates existence of a secondary response
      effected by antibodies. Both responses induced a significantly elevated
      expression of the Th2 signature cytokine Il13. The increased presence of
      neutrophils in immunized fish suggests that innate cell mediated immunity
      supplements or influence the protective response against the parasite.

PMID- 30204773
TI  - Training of clinical reasoning with a Serious Game versus small-group problem
      based learning: A prospective study.
AB  - INTRODUCTION: Serious Games are increasingly being used in undergraduate medical
      education. They are usually intended to enhance learning with a focus on
      knowledge acquisition and skills development. According to the current
      literature, few studies have assessed their effectiveness regarding clinical
      reasoning (CR). The aim of this prospective study was to compare a Serious Game,
      the virtual Accident & Emergency department 'EMERGE' to small-group problem-based
      learning (PBL) regarding student learning outcome on clinical reasoning in the
      short term. METHODS: A total of 112 final-year medical students self-selected to
      participate in ten 90-minute sessions of either small-group PBL or playing
      EMERGE. CR was assessed in a formative examination consisting of six key feature
      cases and a final 45-minute EMERGE session. RESULTS: Overall, the EMERGE group (n
      = 78) scored significantly higher than the PBL group (n = 34) in the key feature
      examination (62.5 (IQR: 17.7)% vs. 54.2 (IQR: 21.9)%; p = 0.015). There was no
      significant difference in performance levels between groups regarding those cases
      which had been discussed in both instructional formats during the training phase.
      In the final EMERGE session, the EMERGE group achieved significantly better
      results than the PBL group in all four cases regarding the total score as well as
      in three of four cases regarding the final diagnosis and the correct therapeutic
      interventions. CONCLUSION: EMERGE can be used effectively for CR training in
      undergraduate medical education. The difference in key feature exam scores was
      driven by additional exposure to more cases in EMERGE compared to PBL despite
      identical learning time in both instructional formats. EMERGE is a potential
      alternative to intensive small-group teaching. Further work is needed to
      establish how Serious Games enhance CR most effectively.

PMID- 30204774
TI  - Relational encoding of objects in working memory: Changes detection performance
      is better for violations in group relations.
AB  - Research has indicated that working memory is based on forming relations between
      individual elements. In this study, we considered the congruency of object
      clusters during a change detection task. We demonstrate that changes which
      violate the relational encoding of a probe display (single-object changes where
      one object shifts independently from its corresponding group) are more easily
      detected than changes that maintain group structure (cluster changes where all
      objects in the group shift in location together)-despite cluster changes
      involving more objects moving overall. We explore this effect across interactions
      with direction of single-object movement (distancing from the cluster vs. uniting
      with the cluster) and trial order, demonstrating that naive participants improve
      at a faster rate on single-object changes than cluster changes. It is concluded
      that storage in working memory functions by building relational bindings between
      objects and their place within the chunk, rather than by binding objects to their
      spatial location.

PMID- 30204775
TI  - Self-esteem in the deaf who have become cochlear implant users as adults.
AB  - OBJECTIVE: Self-esteem is a good predictor of mental health and is crucial for
      well-being and psychological functioning. It is especially important in
      situations where there are potential mental health problems, such as in people
      suffering from hearing loss or total deafness. This study aims to gauge the level
      of self-esteem in adults with hearing problems, in particular those who, in
      adulthood, had received a cochlear implant (CI). The subjects had different onset
      (pre-lingual/post-lingual) and amount (deafness/partial deafness) of hearing
      loss, and their current level of self-esteem was compared to that of the general
      population. The association of self-esteem with other deafness-related variables
      (e.g. satisfaction with their CI or whether they also used a hearing aid) and
      sociodemographic factors was also investigated. METHODS: Data were obtained from
      questionnaires mailed to patients who, when adult, had received a CI. The
      subjects were divided into four subgroups: subjects with pre-lingual deafness,
      post-lingual deafness, pre-lingual partial deafness, and post-lingual partial
      deafness. To evaluate their self-esteem, the Rosenberg Self-Esteem Scale (RSES)
      was used. For data on sociodemographic status and information related to deafness
      and CI, we used our own Information Inquiry form. For statistical analysis of the
      results, we compared means (t-test, ANOVA), investigated correlations, and
      applied linear regression. RESULTS: The self-esteem of deaf and partially deaf CI
      users was significantly lower than in the general population, especially for post
      lingually deafened subjects. The only factor related to deafness and CIs that
      explained self-esteem was self-rated satisfaction with the CI-meaning that higher
      satisfaction was associated with higher self-esteem. The major sociodemographic
      factor that explained self-esteem was marital/partnership status (being in a
      relationship was helpful). Also men had higher self-esteem than women. Those with
      higher levels of education, and those working or studying, had higher self-esteem
      than those who did not. RSES was found to have a single-factor structure.
      CONCLUSION: Deafness and partial deafness appear to be risk factors for lower
      self-esteem, a finding that rehabilitation, medical, educational, and employment
      communities should be made aware of. Medical intervention in the form of a CI
      supplies the person with improved hearing, but it is not a panacea: their self
      esteem is still vulnerable, and reinforcement of self-esteem is an aspect that
      professionals should focus on. Psychological, psycho-educational, and
      psychotherapeutic interventions have important roles to play for CI recipients.

PMID- 30204778
TI  - Distribution of the Unionida (Bivalvia, Paleoheterodonta) from Argentina and its
      conservation in the Southern Neotropical Region.
AB  - Bivalves are one of the most representative groups in the Phylum Mollusca, with
      over 1,100 freshwater species around the world except Antarctica. About 900 of
      these species belong to the Order Unionida Gray, 1854. In South America, the
      distributional range of the Unionida includes all countries in the region and
      extends as far south as the lakes and rivers of Argentinean-Chilean Patagonia.
      With the aim of generating distribution maps for the different genera of Unionida
      in Argentina, we consulted the databases of the nation's main official
      malacological collections. The data were analyzed and georeferenced using the
      point-radius method. Spatial analyses were performed with the software Q-GIS
      2.16.3 Nodebo using vector layers under the 2007 Argentinean Geodesic Positions
      reference system. A total 1,833 lots were analyzed, of which it was possible to
      georeference 1,503. The distribution of Unionida in Argentinean territory was
      analyzed according to political provinces, Surface Drainage Basins and the
      Argentinean Protected Areas. Species richness was analyzed using the surface
      drainage basins of Argentina. We generate distribution maps for each genus and
      discuss the species threat status and conservation degree in the region. Only six
      (18%) of the Unionida present in Argentina have been classified by the IUCN, four
      are Least Concern and two are Data Deficient. This pattern is also valid for all
      of South America. More than 95% of the distributional range of the Unionida has
      no protected area. Conservation management is necessary for the preservation of
      Unionida diversity in southern South America.

PMID- 30204777
TI  - Complication patterns in patients undergoing venoarterial extracorporeal membrane
      oxygenation in intensive care unit: Multiple correspondence analysis and
      hierarchical ascendant classification.
AB  - BACKGROUND: Treatment by venoarterial extracorporeal membrane oxygenation (VA
      ECMO) is widely used today, even though it is associated with high risks of
      complications and death. While studies have focused on the relationship between
      some of these complications and the risk of death, the relationship between
      different complications has never been specifically examined, despite the fact
      that the occurrence of one complication is known to favor the occurrence of
      others. Our objective was to describe the relationship between complications in
      patients undergoing VA-ECMO in intensive care unit (ICU) and to identify, if
      possible, patterns of patients according to complications. METHODS AND FINDINGS:
      As part of a retrospective cohort study, we conducted a multiple correspondence
      analysis followed by a hierarchical ascendant classification in order to identify
      patterns of patients according to main complications (sepsis, thromboembolic
      event, major transfusion, major bleeding, renal replacement therapy) and in-ICU
      death. Our cohort of 145 patients presented an in-ICU mortality rate of 50.3%.
      Morbidity was high, with 36.5% of patients presenting three or more of the five
      complications studied. Multiple correspondence analysis revealed a cumulative
      inertia of 76.9% for the first three dimensions. Complications were clustered
      together and clustered close to death, prompting the identification of four
      patterns of patients according to complications, including one with no
      complications. CONCLUSIONS: Our study, based on a large cohort of patients
      undergoing VA-ECMO in ICU and presenting a mortality rate comparable to that
      reported in the literature, identified numerous and often interrelated
      complications. Multiple correspondence analysis and hierarchical ascendant
      classification yielded clusters of patients and highlighted specific links
      between some of the complications studied. Further research should be conducted
      in this area.

PMID- 30204776
TI  - The Salmonella type-3 secretion system-1 and flagellar motility influence the
      neutrophil respiratory burst.
AB  - Neutrophils are innate immune response cells designed to kill invading
      microorganisms. One of the mechanisms neutrophils use to kill bacteria is
      generation of damaging reactive oxygen species (ROS) via the respiratory burst.
      However, during enteric salmonellosis, neutrophil-derived ROS actually
      facilitates Salmonella expansion and survival in the gut. This seeming paradox
      led us to hypothesize that Salmonella may possess mechanisms to influence the
      neutrophil respiratory burst. In this work, we used an in vitro Salmonella
      neutrophil co-culture model to examine the impact of enteric infection relevant
      virulence factors on the respiratory burst of human neutrophils. We report that
      neutrophils primed with granulocyte-macrophage colony stimulating factor and
      suspended in serum containing complement produce a robust respiratory burst when
      stimulated with viable STm. The magnitude of the respiratory burst increases when
      STm are grown under conditions to induce the expression of the type-3 secretion
      system-1. STm mutants lacking the type-3 secretion system-1 induce less
      neutrophil ROS than the virulent WT. In addition, we demonstrate that flagellar
      motility is a significant agonist of the neutrophil respiratory burst. Together
      our data demonstrate that both the type-3 secretion system-1 and flagellar
      motility, which are established virulence factors in enteric salmonellosis, also
      appear to directly influence the magnitude of the neutrophil respiratory burst in
      response to STm in vitro.

PMID- 30204779
TI  - The angiotensin II/AT1 receptor pathway mediates malaria-induced acute kidney
      injury.
AB  - Malaria-induced acute kidney injury (MAKI) is a life-threatening complication of
      severe malaria. Here, we investigated the potential role of the angiotensin II
      (Ang II)/AT1 receptor pathway in the development of MAKI. We used C57BL/6 mice
      infected by Plasmodium berghei ANKA (PbA-infected mice), a well-known murine
      model of severe malaria. The animals were treated with 20 mg/kg/day losartan, an
      antagonist of AT1 receptor, or captopril, an angiotensin-converting enzyme
      inhibitor. We observed an increase in the levels of plasma creatinine and blood
      urea nitrogen associated with a significant decrease in creatinine clearance, a
      marker of glomerular flow rate, and glomerular hypercellularity, indicating
      glomerular injury. PbA-infected mice also presented proteinuria and a high level
      of urinary gamma-glutamyltransferase activity associated with an increase in
      collagen deposition and interstitial space, showing tubule-interstitial injury.
      PbA-infected mice were also found to have increased fractional excretion of
      sodium (FENa+) coupled with decreased cortical (Na++K+)ATPase activity. These
      injuries were associated with an increase in pro-inflammatory cytokines, such as
      tumor necrosis factor alpha, interleukin-6, interleukin-17, and interferon gamma,
      in the renal cortex of PbA-infected mice. All modifications of these structural,
      biochemical, and functional parameters observed in PbA-infected mice were avoided
      with simultaneous treatment with losartan or captopril. Our data allow us to
      postulate that the Ang II/AT1 receptor pathway mediates an increase in renal pro
      inflammatory cytokines, which in turn leads to the glomerular and tubular
      injuries observed in MAKI.

PMID- 30204780
TI  - Chronic fatigue syndrome patients have alterations in their oral microbiome
      composition and function.
AB  - Host-microbe interactions have been implicated in the pathogenesis of chronic
      fatigue syndrome (CFS), but whether the oral microbiome is altered in CFS
      patients is unknown. We explored alterations of the oral microbiome in Chinese
      Han CFS patients using 16S rRNA gene sequencing and alterations in the functional
      potential of the oral microbiome using PICRUSt. We found that Shannon and Simpson
      diversity indices were not different in CFS patients compared to healthy
      controls, but the overall oral microbiome composition was different (MANOVA, p <
      0.01). CFS patients had a higher relative abundance of Fusobacteria compared with
      healthy controls. Further, the genera Leptotrichia, Prevotella, and Fusobacterium
      were enriched and Haemophilus, Veillonella, and Porphyromonas were depleted in
      CFS patients compared to healthy controls. Functional analysis from inferred
      metagenomes showed that bacterial genera altered in CFS patients were primarily
      associated with amino acid and energy metabolism. Our findings demonstrate that
      the oral microbiome in CFS patients is different from healthy controls, and these
      differences lead to shifts in functional pathways with implications for CFS
      pathogenesis. These findings increase our understanding of the relationship
      between the oral microbiota and CFS, which will advance our understanding of CFS
      pathogenesis and may contribute to future improvements in treatment and
      diagnosis.

PMID- 30204781
TI  - Aqueous humor cytokine levels in patients with diabetic macular edema refractory
      to anti-VEGF treatment.
AB  - PURPOSE: To determine aqueous cytokines association with response to intravitreal
      bevacizumab (IVB) injection in diabetic macular edema (DME). METHOD: We compared
      the concentrations of IL (interleukin)-1beta, IL-2, IL-8, IL-10, IL-17, placental
      growth factor (PlGF), and vascular endothelial growth factor (VEGF) in the
      aqueous humor of 64 naive DME patients with those of 13 cataract patients.
      Factors associated with central subfield thickness (CST) in DME patients were
      identified. DME patients were then subgrouped in terms of responsiveness to three
      IVB injections; cytokine concentrations were compared, and factors associated
      with responsiveness were identified. RESULTS: Levels of IL-2, IL-8, PlGF, and
      VEGF were significantly elevated in DME patients (p = 0.007, p < 0.001, p <
      0.001, and p = 0.004 respectively). Regression analysis showed that the
      preoperative CST was associated with the preoperative best-corrected visual
      acuity and the aqueous IL-10 level (p < 0.001, p = 0.006, respectively). Of the
      64 DME patients, 28 (43.75%) exhibited either CST < 300 MUm or reduction in CST
      >= 50 MUm after three consecutive IVB injections. On sub-group analysis, the mean
      IL-8 concentration was higher in the refractory group than in the responsive
      group, and multivariate logistic regression analysis showed that the IL-8 was the
      only factor associated with responsiveness (OR = 0.95, p = 0.017). CONCLUSIONS:
      The IL-8 concentration in the aqueous humor was associated with responsiveness to
      IVB in DME patients.

PMID- 30204782
TI  - Extended antibiotic treatment in salmon farms select multiresistant gut bacteria
      with a high prevalence of antibiotic resistance genes.
AB  - The high use of antibiotics for the treatment of bacterial diseases is one of the
      main problems in the mass production of animal protein. Salmon farming in Chile
      is a clear example of the above statement, where more than 5,500 tonnes of
      antibiotics have been used over the last 10 years. This has caused a great impact
      both at the production level and on the environment; however, there are still few
      works in relation to it. In order to demonstrate the impact of the high use of
      antibiotics on fish gut microbiota, we have selected four salmon farms presenting
      a similar amount of fish of the Atlantic salmon species (Salmo salar), ranging
      from 4,500 to 6,000 tonnes. All of these farms used treatments with high doses of
      antibiotics. Thus, 15 healthy fish were selected and euthanised in order to
      isolate the bacteria resistant to the antibiotics oxytetracycline and florfenicol
      from the gut microbiota. In total, 47 bacterial isolates resistant to florfenicol
      and 44 resistant to oxytetracycline were isolated, among which isolates with
      Minimum Inhibitory Concentrations (MIC) exceeding 2048 MUg/mL for florfenicol and
      1024 MUg/mL for oxytetracycline were found. In addition, another six different
      antibiotics were tested in order to demonstrate the multiresistance phenomenon.
      In this regard, six isolates of 91 showed elevated resistance values for the
      eight tested antibiotics, including florfenicol and oxytetracycline, were found.
      These bacteria were called "super-resistant" bacteria. This phenotypic resistance
      was verified at a genotypic level since most isolates showed antibiotic
      resistance genes (ARGs) to florfenicol and oxytetracycline. Specifically, 77% of
      antibiotic resistant bacteria showed at least one gene resistant to florfenicol
      and 89% showed at least one gene resistant to oxytetracycline. In the present
      study, it was demonstrated that the high use of the antibiotics florfenicol and
      oxytetracycline has, as a consequence, the selection of multiresistant bacteria
      in the gut microbiota of farmed fish of the Salmo salar species at the seawater
      stage. Also, the phenotypic resistance of these bacteria can be correlated with
      the presence of antibiotic resistance genes.

PMID- 30204784
TI  - Viewpoints of pedestrians with and without cognitive impairment on shared zones
      and zebra crossings.
AB  - BACKGROUND: Shared zones are characterised by an absence of traditional markers
      that segregate the road and footpath. Negotiation of a shared zone relies on an
      individual's ability to perceive, assess and respond to environmental cues. This
      ability may be impacted by impairments in cognitive processing, which may lead to
      individuals experiencing increased anxiety when negotiating a shared zone.
      METHOD: Q method was used in order to identify and explore the viewpoints of
      pedestrians, with and without cognitive impairments as they pertain to shared
      zones. RESULTS: Two viewpoints were revealed. Viewpoint one was defined by
      "confident users" while viewpoint two was defined by users who "know what [they]
      are doing but drivers might not". DISCUSSION: Overall, participants in the study
      would not avoid shared zones. Pedestrians with intellectual disability were,
      however, not well represented by either viewpoint, suggesting that shared zones
      may pose a potential barrier to participation for this group.

PMID- 30204783
TI  - Adverse prognostic impact of splenectomy on survival in gastric carcinoma
      patients: Regression and propensity score matching analysis of 1074 patients.
AB  - BACKGROUNDS: Patients with proximal gastric carcinoma undergo total gastrectomy
      with concomitant splenectomy to ensure the complete removal of splenic hilar
      lymph nodes. However, the impact of splenectomy on survival remains uncertain.
      This study aimed to investigate the impact of splenectomy on survival among
      patients with gastric carcinoma. METHODS: Of 1074 patients who underwent total
      gastrectomy for proximal gastric carcinoma between 2006 and 2014, 229 patients
      underwent concomitant splenectomy or pancreaticosplenectomy during surgery. We
      investigated the prognostic impact of splenectomy using a regression and
      propensity score matched model. RESULTS: The splenectomy and non-splenectomy
      groups differed in many baseline characteristics, including tumor stage, and had
      respective crude 5-year survival rates of 55% and 81% (p <0.001). In a
      multivariate analysis adjusted for TNM stage and other prognostic factors,
      splenectomy was an independent poor prognostic factor for overall survival
      (hazard ratio [HR] = 1.67, 95% confidence interval [CI] = 1.11-2.51) and disease
      free survival (HR = 1.61, 95% CI = 1.24-2.10). A survival evaluation stratified
      by TNM stage showed that splenectomy adversely affected survival among patients
      with stage III, but not stage I, II, and IV disease. In the propensity score
      matched sample, splenectomy group also showed significantly worse overall
      survival (5-year, 65% vs. 79%, p = 0.010) and disease-free survival (5-year, 55%
      vs. 72%, p = 0.025) and was an independent poor prognostic factor in a
      multivariate analysis adjusting TNM stage and other prognostic factors.
      CONCLUSIONS: Splenectomy adversely affects survival, particularly among patients
      with stage III gastric carcinoma, and should be avoided unless there is direct
      invasion to the splenic hilum.

PMID- 30204786
TI  - Resilience of and recovery strategies for weighted networks.
AB  - The robustness and resilience of complex networks have been widely studied and
      discussed in both research and industry because today, the diversity of system
      components and the complexity of the connection between units are increasingly
      influencing the reliability of complex systems. Previous studies have focused on
      node failure in networks, proposing several performance indicators. However, a
      single performance indicator cannot comprehensively measure all the performance
      aspects; thus, the selected performance indicators and recovery strategies lack
      consistency with respect to the targeted complex systems. This paper introduces a
      novel stress-strength-balanced weighted network model based on two network
      transmission hypotheses. Then, with respect to different concerns of the complex
      network, we propose two modified network performance measurement indicators and
      compare these indicators in terms of their trends in the attack process. In
      addition, we introduce several network recovery strategies and compare their
      efficiencies. Our findings are as follows: (1) The evaluation and judgment of the
      network performance depend on the performance measurement indicators we use. (2)
      Different recovery strategies exhibit distinct efficiencies in recovering
      different aspects of network performance, and no strategy exists that can improve
      all the network performance aspects simultaneously. (3) The timing of the
      recovery is proved to have a deep influence on the cost and efficiency of network
      recovery; thus, the optimal recovery strategy for a damaged network varies with
      the extent of the damage. From the results of the simulation of the attack
      recovery process, we conclude that while defining and analyzing complex network
      models, we should adjust our network topology, weight assignment, and performance
      indicators in accordance with the focal characteristics of complex systems so
      that we can use the network model to build robust complex systems and efficient
      logistics and maintenance strategies.

PMID- 30204785
TI  - The effects of aerobic exercise on eGFR, blood pressure and VO2peak in patients
      with chronic kidney disease stages 3-4: A systematic review and meta-analysis.
AB  - BACKGROUND: CKD is associated with several comorbidities, cardiovascular disease
      being the most significant. Aerobic training has a beneficial effect on
      cardiovascular health in healthy and some well-defined non-healthy populations.
      However, the effect of aerobic training on glomerular filtration rate in patients
      with CKD stages 3-4 is unclear. OBJECTIVE: To review the effects of aerobic
      exercise training on kidney and cardiovascular function in patients with chronic
      kidney disease (CKD) stages 3-4. METHODS: A random-effects meta-analysis was
      performed to analyse published randomized controlled trials through February 2018
      on the effect of aerobic training on estimated glomerular filtration rate, blood
      pressure and exercise tolerance in patients with CKD stages 3-4. Web of Science,
      PubMed and Embase databases were searched for eligible studies. RESULTS: 11
      randomized controlled trials were selected including 362 participants in total.
      Favourable effects were observed on estimated glomerular filtration rate (+2.16
      ml/min per 1.73m2; [0.18; 4.13]) and exercise tolerance (+2.39 ml/kg/min; [0.99;
      3.79]) following an on average 35-week aerobic training program when compared to
      standard care. No difference in change in blood pressure was found. CONCLUSIONS:
      There is a small beneficial effect of aerobic training on estimated glomerular
      filtration rate and exercise tolerance, but not on blood pressure, in patients
      with CKD stages 3-4. However, data are limited and pooled findings were rated as
      of low to moderate quality.

PMID- 30204788
TI  - The VAChTY49N mutation provides insecticide-resistance but perturbs evoked
      cholinergic neurotransmission in Drosophila.
AB  - Global agriculture and the control of insect disease vectors have developed with
      a heavy reliance on insecticides. The increasing incidence of resistance, for
      virtually all insecticides, threatens both food supply and effective control of
      insect borne disease. CASPP ((5-chloro-1'-[(E)-3-(4
      chlorophenyl)allyl]spiro[indoline-3,4'-piperidine]-1-yl}-(2-chloro-4
      pyridyl)methanone)) compounds are a potential new class of neuroactive
      insecticide specifically targeting the Vesicular Acetylcholine Transporter
      (VAChT). Resistance to CASPP, under laboratory conditions, has been reported
      following either up-regulation of wildtype VAChT expression or the presence of a
      specific point mutation (VAChTY49N). However, the underlying mechanism of CASPP
      resistance, together with the consequence to insect viability of achieving
      resistance, is unknown. In this study, we use electrophysiological
      characterisation of cholinergic release at Drosophila larval interneuron
      >motoneuron synapses to investigate the physiological implications of these two
      identified modes of CASPP resistance. We show that both VAChT up-regulation or
      the expression of VAChTY49N increases miniature (mini) release frequency. Mini
      frequency appears deterministic of CASPP activity. However, maintenance of SV
      release is not indicative of resistance in all cases. This is evidenced through
      expression of syntaxin or complexin mutants (sytx3-61/cpxSH1) that show similarly
      high mini release frequency but are not resistant to CASPP. The VAChTY49N
      mutation additionally disrupts action potential-evoked cholinergic release and
      fictive locomotor patterning through depletion of releasable synaptic vesicles.
      This observation suggests a functional trade-off for this point mutation, which
      is not seen when wildtype VAChT is up-regulated.

PMID- 30204789
TI  - Interaction network analysis of the six game complexes in high-level volleyball
      through the use of Eigenvector Centrality.
AB  - Social Network Analysis establishes a network system and provides information
      about the relationships (edges) between system components (nodes). Although nodes
      usually correspond to actors within the network (e.g., the players), it is
      possible to stipulate game actions as nodes, thus creating a network of the flow
      of game actions. In this study, Eigenvector Centrality (a form of weighted
      centrality that considers n-order connections) was used to identify differences
      in the centrality of distinct game actions within each of the six game complexes
      of volleyball. Thirteen matches (46 sets, 2,049 rallies) of the final round of
      the 2015 FIVB's World Grand Prix (Women) were analyzed. Results showed that
      analyzing actions as actors (i.e., nodes) offers a clear and comprehensive
      understanding of game flow and poses an interesting alternative to mainstream
      research where players are considered nodes. Functional differences between the
      six game complexes were highlighted, denoting the validity of such division. Out
      of-system playing (i.e., having to set the attack under non-ideal conditions,
      e.g., in KI, KII, KIII and KIV), emerged as a regularity of the game and should
      be translated into the training process.

PMID- 30204787
TI  - Characterization of immune responses of human PBMCs infected with Mycobacterium
      tuberculosis H37Ra: Impact of donor declared BCG vaccination history on immune
      responses and M. tuberculosis growth.
AB  - This study characterized the immune responses in early Mycobacterium tuberculosis
      (Mtb) H37Ra infection of human peripheral blood mononuclear cell (PBMC)-collagen
      matrix culture and the impact of Bacille Calmette-Guerin (BCG) vaccination
      history of donor PBMCs on the immune responses to Mtb infection. Aggregates of
      PBMCs were initially observed on day 3 and the size of aggregates continued to
      increase on day 8 post-infection, where macrophages and T cell subsets were
      identified to be present. Similarly, mycobacterial load progressively increased
      in infected PBMCs during the 8 days of culture but were significantly lower in
      infected PBMCs from BCG vaccinated (BCG+) donors compared to unvaccinated (BCG-)
      donors. The levels of INF-gamma, TNF-alpha, IL-4, IL-6, IL-10 and IL-17 in the
      supernatants of Mtb-infected PBMCs peaked at day 3 and decreased on days 5 and 8.
      The levels of these cytokines except IL-10 were significantly lower in Mtb
      infected PBMCs from BCG+ donors compared to infected PBMCs from BCG- donors. The
      percentages of activated naive Th cells, activated effector memory Th cells and
      activated central memory Tc cells were significantly higher in Mtb-infected PBMCs
      compared to uninfected PBMCs at day 8 post-infection. Further, the proportion of
      activated central memory Tc cells was significantly higher in infected PBMCs from
      BCG+ donors compared to the BCG- donors. This study highlights the possibility
      that BCG vaccination may confound results that utilize human PBMCs to study Mtb
      infection.

PMID- 30204790
TI  - Effect of nocturnal hemodialysis on sleep parameters in patients with end-stage
      renal disease: a systematic review and meta-analysis.
AB  - INTRODUCTION: Recently, a small but growing literature has depicted the
      beneficial effects of nocturnal hemodialysis (NHD) over conventional hemodialysis
      (CHD) in the fields of sleep disorders such as sleep apnea. The impact of various
      dialysis models on sleep disorders, however, has not been determined. The
      objective of our meta-analysis is to examine the potential effects of NHD,
      compared with CHD, on sleep disorders in HD patients. METHODS: Several electronic
      databases including PubMed, EMBASE, Cochrane Central Register of Controlled
      Trials, ClinicalTrials.gov and CNKI were searched, using the search terms
      "nocturnal" (or "nightly") and "dialysis" (or "hemodialysis" or "renal dialysis")
      from the earliest available date of indexing to March 2018. Two authors
      independently extracted data, evaluated the study quality, and conducted random
      effects meta-analyses using STATA 12.0. RESULTS: Of 1789 potentially relevant
      citations, 9 fulfilled eligibility criteria, consisting of 6 single-arm studies
      (comparing pre- and post-intervention outcomes), 1 observational study, and 2
      randomized controlled trials (a total of 286 participants). Regarding objective
      sleep assessments, conversion from CHD to NHD resulted in a significant reduction
      in the AHI (Mean difference was -14.90; 95% CI, -20.12 to -9.68), a significant
      increase of SaO2 (Mean difference was 1.38%; 95% CI, 0.35% to 2.42%), and a
      significant decrease of TST (Mean difference was -0.31; 95% CI, -0.47 to -0.15).
      The trends were even stronger in the HD patients with sleep disorders. However,
      regarding subjective sleep assessments, improved sleep quality was found in the
      prospective pre-post intervention studies and cohort studies, while no
      significant improvements were found in the randomized controlled trials.
      CONCLUSION: Although a significant improvement of sleep apnea was observed by
      switching from CHD to NHD, it may not yield a net benefit in overall subjective
      sleep quality.

PMID- 30204791
TI  - Evaluating the psychometric quality of school connectedness measures: A
      systematic review.
AB  - INTRODUCTION: There is a need to comprehensively examine and evaluate the quality
      of the psychometric properties of school connectedness measures to inform school
      based assessment and intervention planning. OBJECTIVE: To systematically review
      the literature on the psychometric properties of self-report measures of school
      connectedness for students aged six to 14 years. METHODS: A systematic search of
      five electronic databases and gray literature was conducted. The COnsensus-based
      Standards for the selection of heath Measurement INstruments (COSMIN) taxonomy of
      measurement properties was used to evaluate the quality of studies and a pre-set
      psychometric criterion was used to evaluate the overall quality of psychometric
      properties. RESULTS: The measures with the strongest psychometric properties was
      the School Climate Measure and the 35-item version Student Engagement Instrument
      exploring eight and 12 (of 15) school connectedness components respectively.
      CONCLUSIONS: The overall quality of psychometric properties was limited
      suggesting school connectedness measures available require further development
      and evaluation.

PMID- 30204792
TI  - Correction: Highly-sensitive detection of Salmonella typhi in clinical blood
      samples by magnetic nanoparticle-based enrichment and in-situ measurement of
      isothermal amplification of nucleic acids.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0194817.].

PMID- 30204793
TI  - Seasonal variation of BMI at admission in German adolescents with anorexia
      nervosa.
AB  - OBJECTIVE: Recent preliminary studies indicated a seasonal association of BMI at
      admission to inpatient treatment for anorexia nervosa (AN), indicating lower BMI
      in the cold season for restrictive AN. An impaired thermoregulation was proposed
      as the causal factor, based on findings in animal models of AN. However, findings
      regarding seasonality of BMI and physical activity levels in the general
      population indicate lower BMI and higher physical activity in summer than in
      winter. Therefore, we aimed to thoroughly replicate the findings regarding
      seasonality of BMI at admission in patients with AN in this study. METHOD: AN
      subtype, age- and gender-standardized BMI scores (BMI-SDS) at admission, mean
      daily sunshine duration and ambient temperature at the residency of 304
      adolescent inpatients with AN of the multi-center German AN registry were
      analyzed. RESULTS: A main effect of DSM-5 AN subtype was found (F(2,298) = 6.630,
      p = .002), indicating differences in BMI-SDS at admission between restrictive,
      binge/purge and subclinical AN. No main effect of season on BMI-SDS at admission
      was found (F(1,298) = 4.723, p = .025), but an interaction effect of DSM-5
      subtype and season was obtained (F(2,298) = 6.625, p = .001). Post-hoc group
      analyses revealed a lower BMI-SDS in the warm season for restrictive AN with a
      non-significant small effect size (t(203.16) = 2.140, p = .033; Hedges'g = 0.28).
      Small correlations of mean ambient temperature (r = -.16) and daily sunshine
      duration (r = -.22) with BMI-SDS in restrictive AN were found. However, the data
      were widely scattered. CONCLUSIONS: Our findings are contrary to previous studies
      and question the thermoregulatory hypothesis, indicating that seasonality in AN
      is more complex and might be subject to other biological or psychological
      factors, for example physical activity or body dissatisfaction. Our results
      indicate only a small clinical relevance of seasonal associations of BMI-SDS
      merely at admission. Longitudinal studies investigating within-subject seasonal
      changes might be more promising to assess seasonality in AN and of higher
      clinical relevance.

PMID- 30204794
TI  - Protective immune mechanisms of Yifei Tongluo, a Chinese herb formulation, in the
      treatment of mycobacterial infection.
AB  - Yifei Tongluo (YFTL) is a traditional Chinese medicine (TCM) formulation which
      has been shown clinical efficacy in treatment of patients with multidrug
      resistant tuberculosis in China. However, the underlying mechanisms of the
      effects of YFTL are lacking. This study investigated the effects of YFTL on
      immune regulation with a mouse lung infection model with Bacille Calmette-Guerin
      (BCG). We found that compared with untreated mice, the lung mycobacterial load in
      YFTL-treated mice was significantly reduced, accompanied by alleviated pulmonary
      inflammation with reduction of pro-inflammatory cytokines and increase of
      prostaglandin E2 (PGE2). Flow cytometry analyses showed that Th1 cells were
      significantly higher in the lungs of YFTL-treated mice at early infection time.
      The results suggest that YFTL-treatment down-regulates pulmonary inflammation,
      which facilitates a rapid infiltration of Th1 cells into the lungs. Moreover, the
      Th1 cells in the lungs were resolved faster at later time concomitant with
      increased the regulatory T cells (Tregs). The reduction of mycobacterial burden
      associated with improved tissue pathology, faster Th1 cell trafficking, and
      accelerated resolution of Th1 cells in the lungs of YFTL-treated mice indicates
      that YFTL improves mycobacterial clearance by maintaining lung homeostasis and
      dynamically regulating T cells in the lung parenchyma, and suggests that YFTL can
      be used as host-directed therapies that target immune responses to mycobacterial
      infection.

PMID- 30204795
TI  - Relationship between low levels of circulating TRAIL and atheromatosis
      progression in patients with chronic kidney disease.
AB  - BACKGROUND: Chronic kidney disease (CKD) patients experience a high risk of
      cardiovascular disease (CV); however, the factors involved in CV-related
      morbidity and mortality in these patients have not been fully defined. Tumor
      necrosis factor related apoptosis-inducing ligand (TRAIL) is a cytokine, which
      exhibits pleiotropic activities on endothelial, vascular smooth muscle and
      inflammatory cells, with relevant effects on atheromatous plaque formation. On
      this basis, the present study aims to investigate the role of TRAIL in
      atheromatosis progression in CKD patients. METHODS: Circulating TRAIL levels were
      measured in 378 CKD patients belonging to the Spanish National Observatory of
      Atherosclerosis in Nephrology (NEFRONA) study. All patients were free of previous
      CV events. Carotid and femoral B-mode ultrasound was performed to detect the
      presence of plaque at baseline and after 24 months of follow-up. RESULTS: The
      lowest levels of TRAIL at baseline were significantly (p<0.05) associated with
      the appearance, after 24 months of follow-up, of at least two new atheromatous
      plaques in all territories and of one new plaque in the carotid artery, even
      after adjusting for CV risk factors. In addition, the patients with low levels of
      TRAIL at baseline were characterized by the presence of at least one hypoechoic
      plaque in the carotid artery. This association was significant (p<0.05) even
      after adjusting for CKD stage. CONCLUSIONS: Overall, the results of our study
      suggest TRAIL as an assertable independent prognostic biomarker for atheromatosis
      plaque formation in CKD patients. This observation further supports the potential
      role of TRAIL for the prevention/treatment of CV disease.

PMID- 30204796
TI  - Identification of a putative novel genotype 3/rabbit hepatitis E virus (HEV)
      recombinant.
AB  - Hepatitis E virus (HEV) is a viral pathogen transmitted by the fecal-oral route
      and is a major cause of waterborne acute hepatitis in many developing countries.
      In addition to infecting humans, HEV has been identified in swine, wild boars,
      rabbits and other mammals; with swine and wild boars being main reservoirs for
      zoonotic transmission of HEV. There are four major HEV genotypes known to infect
      humans; genotypes 1 (HEV-1) and 2 (HEV-2) are restricted to humans, and genotypes
      3 (HEV-3) and 4 (HEV-4) are zoonotic. Herein, three human HEV strains originating
      in France were sequenced and near full-length genomes were characterized.
      Phylogenetic analysis showed that two strains were genotype 3 and closely grouped
      (a 100% bootstrap value) with subtype 3i reference strains. In percent nucleotide
      identities, these two strains were 94% identical to each other, 90-93% identical
      to subtype 3i strains, 82-86% identical to other HEV-3, and 77-79% identical to
      rabbit HEV strains excluding the two divergent strains KJ013414 and KJ013415
      (74%); these two strains were less than 77% identical to strains of HEV genotypes
      1, 2 and 4. The third strain was found distinct from any known HEV strains in the
      database, and located between the clusters of HEV-3 and rabbit HEV strains. This
      unique strain was 74-75% identical to HEV-1, 73% to HEV-2, 81-82% to HEV-3, 77
      79% to rabbit HEV again excluding the two divergent strains KJ013414 and KJ013415
      (74%), and 74-75% to HEV-4, suggesting a novel unclassified strain associated
      with HEV-3 and rabbit HEV. SimPlot and BootScan analyses revealed a putative
      recombination of HEV-3 and rabbit HEV sequences at four breakpoints. Phylogenetic
      trees of the five fragments of the genome confirmed the presence of two HEV-3
      derived and three unclassified sequences. Analyses of the amino acid sequences of
      the three open reading frames (ORF1-3) encoded proteins of these three novel
      strains showed that some amino acid residues specific to rabbit HEV strains were
      found solely in this unclassified strain but not in the two newly identified
      genotype 3i strains. The results obtained by SimPlots, BootScans, phylogenetic
      analyses, and amino acid sequence comparisons in this study all together appear
      to suggest that this novel unclassified strain is likely carrying a mosaic genome
      derived from HEV-3 and rabbit HEV sequences, and is thus designated as a putative
      genotype 3/rabbit HEV recombinant.

PMID- 30204797
TI  - A novel group A rotavirus associated with acute illness and hepatic necrosis in
      pigeons (Columba livia), in Australia.
AB  - Cases of vomiting and diarrhoea were reported in racing pigeons in Western
      Australia in May, 2016. Morbidity and mortality rates were high. Similar clinical
      disease was seen in Victoria in December and by early 2017 had been reported in
      all states except the Northern Territory, in different classes of domestic pigeon
      racing, fancy and meat bird-and in a flock of feral pigeons. Autopsy findings
      were frequently unremarkable; histological examination demonstrated significant
      hepatic necrosis as the major and consistent lesion, often with minimal
      inflammatory infiltration. Negative contrast tissue suspension and thin section
      transmission electron microscopy of liver demonstrated virus particles consistent
      with a member of the Reoviridae. Inoculation of trypsin-treated Vero, MDBK and MA
      104 cell lines resulted in cytopathic changes at two days after infection. Next
      generation sequencing was undertaken using fresh liver samples and a previously
      undescribed group A rotavirus (genotype G18P[17]) of avian origin was identified
      and the virus was isolated in several cell lines. A q-RT-PCR assay was developed
      and used to screen a wider range of samples, including recovered birds. Episodes
      of disease have continued to occur and to reoccur in previously recovered lofts,
      with variable virulence reported. This is the first report of a rotavirus
      associated with hepatic necrosis in any avian species.

PMID- 30204798
TI  - Correlating blood-based DNA methylation markers and prostate cancer risk in
      African-American men.
AB  - The objective of this work was to investigate the clinical significance of
      promoter gene DNA methylation changes in whole blood from African-American (AA)
      men with prostate cancer (PCa). We used high throughput pyrosequencing analysis
      to quantify percentage DNA methylation levels in a panel of 8 genes (RARbeta2,
      TIMP3, SPARC, CDH13, HIN1, LINE1, CYB5R2 and DRD2) in blood DNA obtained from PCa
      and non-cancerous controls cases. Correlations of methylation status and various
      clinicopathological features were evaluated. Six genes tested achieved
      significant difference in DNA methylation levels between the PCa compared to
      control cases (P < 0.05). The TIMP3 loci demonstrated significant correlation of
      DNA methylation with age for all cases analyzed (p < 0.05). We observed an
      inverse correlation between CDH13 methylation (p = 0.045; r = -0.21) and serum
      vitamin D level whereas TIMP3 methylation (p = 0.021; r = -0.24) and DRD2
      methylation (p = 0.056; r = -0.201) showed inverse correlation with supplementary
      vitamin D in the cancer cases. We also observed a direct correlation between
      methylation of RARbeta2 (p = 0.0036; r = 0.293) and SPARC (p = 0.0134; r = 0.20)
      loci with PSA level in the controls but not the cancer cases. In addition,
      alcohol cases significantly correlated with higher RARbeta2 methylation (p =
      0.0314) in comparison with non-alcohol cases. Furthermore, we observed an inverse
      correlation of DRD2 methylation (p = 0.0349; r = -0.343) and Gleason score. Our
      data suggests that promoter methylation occurred more frequently in the blood of
      AA PCa and is associated with various clinicopathological features in AA men with
      PCa.

PMID- 30204799
TI  - Performance of different clinical trial designs to evaluate treatments during an
      epidemic.
AB  - In the 2013-2016 west Africa outbreak of Ebola Virus Disease (EVD), most of the
      planned clinical trials failed to reach a conclusion within the time frame of the
      epidemic. The performance of clinical trial designs for the evaluation of one or
      more experimental treatments in the specific context of an ongoing epidemic with
      changing case fatality rates (CFR) and unpredictable case numbers is unclear. We
      conduct a comprehensive evaluation of commonly used two- and multi-arm clinical
      trial designs based on real data, which was recorded during the 2013-16 EVD
      epidemic in west Africa. The primary endpoint is death within 14 days of
      hospitalization. The impact of the recruitment start times relative to the time
      course of the epidemic on the operating characteristics of the clinical trials is
      analysed. Designs with frequent interim analyses with the possibility of early
      stopping are shown to outperform designs with only a single analysis not only in
      terms of average time to conclusion and average sample size, but also in terms of
      the probability of reaching any conclusion at all. Historic control designs
      almost always result in substantially inflated false positive rates, when the
      case fatality rate changes over time. Response-adaptive randomization may be a
      compromise between the goal of scientific validity and the ethical goal of
      minimizing the number of patients allocated to ineffective treatments.

PMID- 30204800
TI  - How small is TOO small? New liver constraint is needed- Proton therapy of
      hepatocellular carcinoma patients with small normal liver.
AB  - PURPOSE: This study evaluated the outcomes of hepatocellular carcinoma (HCC)
      patients with small normal liver volume (NLV) treated with proton beam therapy
      (PBT) and introduced estimated standard liver volume (eSLV) as a new constraint.
      MATERIALS AND METHODS: HCC patients with NLV < 800 cm3 and no distant metastasis
      who received treatment in our proton center were included. The doses of PBT were
      mainly 72.6 Gray equivalents (GyE) in 22 fractions and 66 GyE in 10 fractions
      according to tumor locations. The Urata equation was used to calculate eSLV.
      RESULTS: Twenty-two patients were treated between November 2015 and December
      2016. The 1-year progression-free and overall survival rates were 40.4% and
      81.8%, respectively. The 1-year in-field failure-free rate was 95.5%. NLV ranged
      from 483.9 to 795.8 cm3 (median = 673.8 cm3), eSLV ranged from 889.3 to 1290.0
      cm3 (median = 1104.5 cm3), and the resulting NLV/eSLV ratio ranged from 44.3 to
      81.2% (median = 57.7%). Non-irradiated liver volume (NILV) ranged from 232.9 to
      531.6 cm3 (median = 391.2 cm3). The NILV/eSLV ratio ranged from 21.2 to 48.0%
      (median = 33.3%). NLV in the patients who received <30 GyE (rV30) ranged from
      319.1 to 633.3 cm3 (median = 488.2 cm3), and their rV30/eSLV ratio ranged from
      30.7 to 58.0%. None of our patients developed liver failure. One patient with
      initial abnormal liver enzyme levels developed non-classic radiation-induced
      liver disease (RILD). CONCLUSION: From the viewpoint of minimal liver toxicity
      occurring in our patients with NLV < 800 cm3, conventional liver constraints
      involving the use of absolute volume could not accurately predict the risk of
      RILD. It is reasonable to start using individualized constraints with eSLV for
      HCC patients undergoing PBT. According to the study results, an NILV/eSLV ratio
      of >20% and an rV30/eSLV ratio of >30% are acceptable.

PMID- 30204802
TI  - Streamflow contributions from tribal lands to major river basins of the United
      States.
AB  - While many studies on tribal water resources of individual tribal lands in the
      United States (US) have been conducted, the importance of tribal water resources
      at a national scale has largely gone unrecognized because their combined totals
      have not been quantified. Thus, we sought to provide a numerical estimate of
      major water budget components on tribal lands within the conterminous US and on
      USGS hydrologic unit codes (HUC2) regions. Using existing national-scale data and
      models, we estimated mean annual precipitation, evapotranspiration, excess
      precipitation, streamflow, and water use for the period 1971-2000. Tribal lands
      represent about 3.4 percent of the total land area of the conterminous US and on
      average account for 1.9 percent of precipitation, 2.4 percent of actual
      evapotranspiration, 0.95 percent of excess precipitation, 1.6 percent of water
      use, and 0.43 percent of streamflow origination. Additionally, approximately 9.5
      and 11.3 percent of US streamflow flows through or adjacent as boundaries to
      tribal lands, respectively. Streamflow through or adjacent to tribal lands
      accounts for 42 and 48 percent of streamflow in the Missouri region,
      respectively; and for 86 and 88 percent in the Lower Colorado region,
      respectively. On average, 5,600 million cubic meters of streamflow per year was
      produced on tribal lands in the Pacific Northwest region, nearly five times
      greater than tribal lands in any other region. Tribal lands in the Great Lakes,
      Missouri, Arkansas-White-Red, and California regions all produced between 1,000
      and 1,400 million cubic meters per year.

PMID- 30204801
TI  - Females of HbAS genotype have reduced concentration of the malaria protective
      deoxyhemoglobin S than males.
AB  - The quantity of the intra-erythrocytic deoxyhemoglobin S (Hb S) affects the level
      of protection against malaria and also the sickling phenomenon. This study
      reports on significantly lower concentration of Hb S in females than males. Data
      came from 350 children, aged 12-47 months who participated in a phase 2b malaria
      vaccine trial. Hemoglobinopathy and G6PD deficiency typing was necessary to
      ascertain equal representation of these malaria protective traits across the
      vaccine cohorts. Hemoglobin types (HbAA, HbAS) and % Hb S were evaluated by HPLC.
      Alpha thalassemia (alpha-thal) and G6PD genotypes were evaluated by PCR. The
      overall prevalence for HbAS was 20%, 46% for 3 alpha genes and 10% for 2 alpha
      genes and 14% for G6PD A-. More females of HbAS/alphaalpha/alphaalpha genotype
      had low Hb S than males and had mean % Hb S of 37.5% +/- 5.4 SD, compared to
      42.0% +/- 2.5 SD in males of same genotype (P = 0.018). Consistent with reduction
      of the malaria protective Hb S in females, parasite load in females was nearly
      twice that of males but the difference was not statistically significant. The X
      chromosome linked G6PD deficiency did not influence the level of Hb S. We
      conclude that, the low Hb S in these females explains the resultant higher
      malaria parasite load. We speculate that the low Hb S in females could also
      explain observations suggesting that the sickling phenomenon tends to be less
      severe in females than males.

PMID- 30204803
TI  - Heart rate variability as predictor of mortality in sepsis: A systematic review.
AB  - BACKGROUND: Autonomic dysregulation is one of the recognized pathophysiological
      mechanisms in sepsis, generating the hypothesis that heart rate variability (HRV)
      can be used to predict mortality in sepsis. METHODS: This was a systematic review
      of studies evaluating HRV as a predictor of death in patients with sepsis. The
      search was performed by independent researchers in PubMed, LILACS and Cochrane,
      including papers in English, Portuguese or Spanish, indexed until August 20th,
      2017 with at least 10 patients. Study quality was assessed by Newcastle-Ottawa
      Scale. To analyze the results, we divided the articles between those who measured
      HRV for short-term recordings (<= 1 hour), and those who did long-term recordings
      (>= 24 hours). RESULTS: Nine studies were included with a total of 536 patients.
      All of them were observational studies. Studies quality varied from 4 to 7 stars
      in Newcastle-Ottawa Scale. The mortality rate in the studies ranged from 8 to
      61%. Seven studies performed HRV analysis in short-term recordings. With the
      exception of one study that did not explain which group had the lowest results,
      all other studies showed reduction of several HRV parameters in the non-survivors
      in relation to the surviving septic patients. SDNN (Standard deviation of the
      Normal to Normal interval), TP (Total Power), VLF (Very Low Frequency Power), LF
      (Low Frequency Power), LF/HF (Low Frequency Power / High Frequency Power), nLF
      (Normalized Low Frequency Power), alpha1/alpha2 (short-term and long-term fractal
      scaling coefficients from DFA) and r-MSSD (Square root of the squared mean of the
      difference of successive NN-intervals) of the non-survivor group were reduced in
      relation to the survivors in at least one study. Two studies found that SDNN is
      associated with mortality in sepsis, even after adjusting for possible
      confounding factors. Three studies performed HRV analysis using long-term
      recordings. Only one of these studies found difference between surviving and non
      surviving groups, and even so, in only one HRV parameter: LogHF. CONCLUSIONS:
      Several HRV parameters are reduced in nonsurviving septic patients in short-term
      recording. Two studies have found that SDNN is associated with mortality in
      sepsis, even after adjusting for possible confounding factors.

PMID- 30204805
TI  - Correction: Experimental research on the structural instability mechanism and the
      effect of multi-echelon support of deep roadways in a kilometre-deep well.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0192470.].

PMID- 30204804
TI  - Parent of origin gene expression in a founder population identifies two new
      candidate imprinted genes at known imprinted regions.
AB  - Genomic imprinting is the phenomena that leads to silencing of one copy of a gene
      inherited from a specific parent. Mutations in imprinted regions have been
      involved in diseases showing parent of origin effects. Identifying genes with
      evidence of parent of origin expression patterns in family studies allows the
      detection of more subtle imprinting. Here, we use allele specific expression in
      lymphoblastoid cell lines from 306 Hutterites related in a single pedigree to
      provide formal evidence for parent of origin effects. We take advantage of phased
      genotype data to assign parent of origin to RNA-seq reads in individuals with
      gene expression data. Our approach identified known imprinted genes, two putative
      novel imprinted genes, PXDC1 and PWAR6, and 14 genes with asymmetrical parent of
      origin gene expression. We used gene expression in peripheral blood leukocytes
      (PBL) to validate our findings, and then confirmed imprinting control regions
      (ICRs) using DNA methylation levels in the PBLs.

PMID- 30204806
TI  - Design and characterization of a synthetic minimal promoter for heterocyst
      specific expression in filamentous cyanobacteria.
AB  - Short and well defined promoters are essential for advancing cyanobacterial
      biotechnology. The heterocyst of Nostoc sp. is suggested as a microbial cell
      factory for oxygen sensitive catalysts, such as hydrogenases for hydrogen
      production, due to its microoxic environment. We identified and predicted
      promoter elements of possible significance through a consensus strategy using a
      pool of heterocyst-induced DIF+ promoters known from Anabaena sp. PCC 7120. To
      test if these conserved promoter elements were crucial for heterocyst-specific
      expression, promoter-yfp reporter constructs were designed. The characterization
      was accomplished by replacing, -35 and -10 regions and the upstream element, with
      well described elements from the trc promoter of Escherichia coli, which is also
      functional in Nostoc sp. From the in vivo spatial fluorescence of the different
      promoter-yfp reporters in Nostoc punctiforme ATCC 29133, we concluded that both
      the consensus -35 and extended -10 regions were important for heterocyst-specific
      expression. Further that the promoter strength could be improved by the addition
      of an upstream element. We designed a short synthetic promoter of 48 nucleotides,
      PsynDIF, including a consensus DIF1 sequence, a 17 base pair stretch of random
      nucleotides and an extended consensus -10 region, and thus generated the shortest
      promoter for heterocyst-specific expression to date.

PMID- 30204807
TI  - Prevalence and trends of polypharmacy among HIV-positive and -negative men in the
      Multicenter AIDS Cohort Study from 2004 to 2016.
AB  - Rates of aging-related comorbidities, which require targeted medications to
      treat, have been shown to be increased among persons living with HIV compared
      with uninfected counterparts. Polypharmacy is generally defined as the concurrent
      use of 5 or more medications. We investigated polypharmacy prevalence for non-HIV
      medications over a 12-year period among HIV-positive and -negative participants
      in the Multicenter AIDS Cohort Study. Information regarding non-HIV medication
      use, HIV status, age, race/ethnicity, enrollment period, and medication insurance
      was obtained on 3,160 participants from semiannual visits between 2004 and 2016.
      Polypharmacy was defined as taking 5 or more non-HIV medications since the last
      health care visit. Generalized estimating equation models with repeated measures
      were produced overall and by HIV status to examine polypharmacy. The unadjusted
      prevalence of polypharmacy across all study visits was 18.6% and was higher among
      HIV-positive participants (24.4%) compared with HIV-negative participants (11.6%)
      (P < .0001). Among the 50 years and older age group, HIV-positive and HIV
      negative participants had increases in polypharmacy over the observation period,
      from 38.4% to 46.8% (P = .0081) and from 16.7% to 46.0% (P < .0001),
      respectively. Among participants younger than 50, polypharmacy among HIV-positive
      participants remained stable (18.9% in 2004 to 17.3% in 2016; P = .5374) but
      increased among HIV-negative men (5.6% to 20.4%; P < .0001). After adjusting for
      age, race/ethnicity, and medication insurance, HIV-positive participants had a
      higher prevalence of polypharmacy than HIV-negative participants (25.3% vs 18.7%;
      P < .0001). Older age, white race, and having medication insurance coverage were
      also associated with greater polypharmacy. A convergence of polypharmacy
      prevalence was observed between HIV-positive and -negative participants at the
      end of observation. HIV-positive status was associated with an increased
      likelihood of polypharmacy, after adjusting for age, race/ethnicity, enrollment
      period, medication insurance, and study visit. Over time, polypharmacy prevalence
      increased among all participants, with converging rates between HIV-positive and 
      negative participants by the end of the observation period.

PMID- 30204808
TI  - Correction: Rad4 Mainly Functions in Chk1-Mediated DNA Damage Checkpoint Pathway
      as a Scaffold Protein in the Fission Yeast Schizosaccharomyces pombe.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0092936.].

PMID- 30204809
TI  - Correction: Correction: AIG1 affects in vitro and in vivo virulence in clinical
      isolates of Entamoeba histolytica.
AB  - [This corrects the article DOI: 10.1371/journal.ppat.1007091.].

PMID- 30204810
TI  - Correction: Periconception Maternal Folate Status and Human Embryonic Cerebellum
      Growth Trajectories: The Rotterdam Predict Study.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0141089.].

PMID- 30204811
TI  - Debonding force and shear bond strength of an array of CAD/CAM-based customized
      orthodontic brackets, placed by indirect bonding- An In Vitro study.
AB  - Based on three-dimensional scanning and computer-aided design and computer-aided
      manufacturing (CAD/CAM) techniques, customized bracket systems are increasingly
      used. However, data remain limited regarding customized bracket design,
      characteristics, and stability. This study was undertaken to evaluate the design,
      bond strength, and residual adhesives of four different CAD/CAM customized
      brackets that were attached to human tooth specimens by indirect bonding. Thirty
      extracted human upper premolars were divided into five groups: Group 1,
      preadjusted self-ligating labial metal bracket; Group 2, lingual self-ligating
      metal injection molding customized bracket; Group 3, gold-casted lingual
      customized bracket; Group 4, labial self-ligating milled customized bracket;
      Group 5, labial customized resin base bracket. Except in Group 1, premolar
      specimens were scanned via model scanner, and the images were sent to each
      manufacturing company to fabricate customized brackets and transfer trays/jigs.
      Debonding force (DF; N) was measured by Instron universal testing machine and
      shear bond strength (SBS; MPa) was calculated via dividing DF by bonding area.
      Adhesive remnants were analyzed via stereo microscopic images. Group 2 (196.90+/
      82.75 N) exhibited significantly higher DF than Group 1 (62.77+/-12.65 N); other
      groups exhibited similar DFs, compared with Group 1. No customized bracket groups
      exhibited significant differences in SBS, relative to Group 1 (6.73+/-1.36 MPa).
      However, SBS in Group 5 (11.46+/-7.22 MPa) was significantly higher than in Group
      3 (3.58+/-2.14 MPa). Group 3 had significantly lower ARI scores than other groups
      (P<0.05). Customized brackets exhibited large deviations in DF and SBS; all
      customized bracket systems exhibited DF that was equivalent or superior to that
      of preadjusted brackets, even when placed by indirect bonding.

PMID- 30204814
TI  - A water-stable lanthanide coordination polymer as a multiresponsive luminescent
      sensor for Fe3+, Cr(vi) and 4-nitrophenol.
AB  - Constructing water stable lanthanide coordination polymers (Ln-CPs) is of great
      importance for practical applications in biological and environmental areas and
      necessary for systematic research on the relationship between the properties of
      Ln-CPs and structures of linker ligands. A two-dimensional (2D) Eu coordination
      polymer (Eu-CP) {[Eu(L)(HCOO)].H2O}n (H2L = isomer of 5-((pyridin-3
      yloxy)methyl)isophthalic acid) is synthesized by the reaction of Eu(NO3)3.6H2O
      and H2L and heating at 140  degrees C. Single crystal X-ray diffraction analysis
      indicates that the Eu-CP presents a 2D network structure formed by binuclear
      metal clusters and bridged linkers COO- and HCOO-. The luminescence properties of
      the Eu-CP are explored at room temperature in the solid-state. The Eu-CP emits
      bright and stable red light due to the antenna effect from the ligand to the
      metal ion. The characteristic emission peaks of Eu3+ can be observed in its
      spectra. The luminescence intensity of the Eu-CP can be sensitively quenched by
      inorganic ions Fe3+, CrO42-, and Cr2O72- and the organic molecule 4-nitrophenol
      (4-NP). The Eu-CP can be a multiresponsive luminescent sensor in the water phase.
      Solvent luminescence investigation and PXRD data demonstrate that the Eu-CP
      exhibits excellent water stability. Therefore, all the sensing experiments are
      carried out in the water system. This multi-responsive luminescent sensor can
      detect Fe3+, Cr(vi) or 4-NP with high sensitivity and low detection limits in
      aqueous solution. Furthermore, the mechanism for the selective sensing of Fe3+,
      Cr(vi) or 4-NP is also explored which can mainly be explained by energy
      competition between the absorption of the analytes and the excitation of the Eu
      CP.

PMID- 30204815
TI  - Collagen formation observed from healing calvarial defects with principal
      component analysis of Raman scattering.
AB  - Bone healing is a complex process involving molecular changes. Bone matrix
      consists of collagen proteins that serve as the framework and minerals, calcium
      and phosphate, are deposited into the matrix accordingly. Raman spectroscopy is a
      promising technique to study bone mineral and matrix environments simultaneously.
      We studied the bone composition using 785 nm excitation during healing of
      subcritical calvarial defects without disrupting the fracture. Calvarial defects
      (in vivo) were created using a 1 mm burr drill on the parietal bones of Sprague
      Dawley rats (n = 12). After 7 days, subjects were sacrificed and an additional
      defect (control) was created. Principal component analysis was utilized for the
      analysis of Raman spectra and helped in classifying normal and healing bone.
      Principal component 1 (PC1) shows that the major variation between in vivo and
      control defects and normal bone surface is at 958 cm-1 (nu1 phosphate band). PC2
      shows a major variation at 1448 cm-1 (CH2 deformation). PC2 score distinguishes
      in vivo defects from normal surface and control defects. The decrease in
      crystallinity and mineral to matrix ratio at the healing site as revealed by
      Raman confirms the new bone formation. Scanning electron and optical microscopy
      show the formation of newly generated matrix by means of bony bridges of
      collagens. The surface roughness increases by 23% from control to in vivo
      defects, as revealed by optical profiler. Histology shows the decreased depth of
      in vivo defects and new blood vessels formation. Overall, the new collagen
      formation shows the scaffolding of the bone is growing during healing.

PMID- 30204812
TI  - Trajectories of quality of life and their association with anxiety in people with
      dementia in nursing homes: A 12-month follow-up study.
AB  - OBJECTIVES: This study aimed to identify possible groups of people with dementia
      (PWD) in nursing homes with different trajectories of proxy-rated quality of life
      (QoL), and to explore how anxiety (along with other characteristics) was
      associated with these trajectories of QoL of PWD in nursing homes at a 12-month
      follow-up. METHODS: We included 298 PWD aged 65 years and older from 17 Norwegian
      nursing homes. The Norwegian version of the Rating Anxiety in Dementia scale
      (RAID-N) was used to assess anxiety, defined as RAID-N score >=12; proxy-rated
      QoL was assessed by Quality of Life in Late-Stage Dementia (QUALID). The
      assessments were made at baseline and after a mean follow-up period of 350 days
      (SD 12.3). A growth mixture model identified two distinct trajectories of QUALID
      scores. Association between the QUALID score trajectories and demographic and
      clinical characteristics were analyzed with logistic regression models. RESULTS:
      Trajectory group 1 (206 participants) had a lower proportion of participants with
      anxiety, and a more stable and better QoL, compared to trajectory group 2 (92
      participants) at a 12-month follow-up. In a multivariate logistic regression
      analysis, more severe impairment in activities of daily living, along with
      presence of anxiety, depression, agitation, and use of antipsychotics at
      baseline, were associated with belonging to the trajectory group with proxy-rated
      poor QoL. SIGNIFICANCES: This study reveals that anxiety is associated with proxy
      rated poor QoL of PWD at a 12-month follow-up. Efforts should be made to identify
      anxiety among nursing home residents with dementia to initiate treatment.

PMID- 30204813
TI  - An automated in vitro motility assay for high-throughput studies of molecular
      motors.
AB  - Molecular motors, essential to force-generation and cargo transport within cells,
      are invaluable tools for powering nanobiotechnological lab-on-a-chip devices.
      These devices are based on in vitro motility assays that reconstitute molecular
      transport with purified motor proteins, requiring a deep understanding of the
      biophysical properties of motor proteins and thorough optimization to enable
      motility under varying environmental conditions. Until now, these assays have
      been prepared manually, severely limiting throughput. To overcome this
      limitation, we developed an in vitro motility assay where sample preparation,
      imaging and data evaluation are fully automated, enabling the processing of a 384
      well plate within less than three hours. We demonstrate the automated assay for
      the analysis of peptide inhibitors for kinesin-1 at a wide range of
      concentrations, revealing that the IAK domain responsible for kinesin-1 auto
      inhibition is both necessary and sufficient to decrease the affinity of the motor
      protein for microtubules, an aspect that was hidden in previous experiments due
      to scarcity of data.

PMID- 30204820
TI  - Potential Relevance of Altered Muscle Activity and Fatigue in the Development of
      Performance-Related Musculoskeletal Injuries in High String Musicians.
AB  - BACKGROUND: Muscle fatigue seems to be a risk factor in the development of
      performance-related musculoskeletal disorders (PRMDs) in musicians, but it is
      unclear how muscle activity characteristics change between musicians with and
      without PRMDs over a prolonged playing period. PURPOSE: To investigate muscle
      activity patterns in muscles of the arms, shoulder, and back of high string
      musicians during prolonged performance. METHODS: Fifteen professional or
      university high string musicians were divided into PRMD and non-PRMD groups. All
      musicians played a chromatic scale, then an individual "heavy" piece for 1 hr,
      and finally the chromatic scale again. Surface electromyography (sEMG) data were
      recorded from 16 muscles of the arm, shoulder, and trunk on both sides of the
      body. Two parameters were analyzed: the percentage load in relation to the
      respective maximum force during the chromatic scale, and the low-frequency
      spectrum to determine the fatigue behavior of muscles during the 1-hr play.
      RESULTS: Changes in muscle activation patterns were observed at the beginning and
      end of the trial duration; however, these varied depending on whether musicians
      had PRMDs or no PRMDs. In addition, low-frequency spectrum changes were observed
      after 1 hr of playing in the PRMD musicians, consistent with signs of muscular
      fatigue. CONCLUSION: Differences in muscle activity appear between high string
      musicians with and without PRMDs as well as altered frequency spectrum shifts,
      suggesting possible differential muscle fatigue effects between the groups. The
      applied sEMG analysis proved a suitable tool for detailed analysis of muscle
      activation characteristics over prolonged playing periods for musicians with and
      without PRMDs.

PMID- 30204821
TI  - Balance Training in Modern Dancers: Proprioceptive-Neuromuscular Training vs
      Kinesio Taping.
AB  - Kinesio tape and proprioceptive exercises are both used for increasing balance in
      dancers. The purposes of this study were to: a) determine the acute effect of
      kinesio tape (KT) application on the ankle joint on balance performance, b)
      investigate the effects of an 8-week proprioceptive-neuromuscular (PN) training
      program on balance performance, and c) compare their effects vs modern dance
      technique classes alone. Thirty-three trained, university-level modern dance
      students (9 male, 24 female) were divided randomly into three groups: kinesio
      tape (KT, n=11), proprioceptive-neuromuscular (PN, n=11), or control (n=11).
      Static (turn-out passe-opened eyes/releve and turn-out passe-closed eyes/flat
      foot), semi-dynamic (airplane), and dynamic balance (monopodalic-straight and 
      transverse in a turn-out passe-eyes opened/flat foot) tests were performed before
      and after the intervention. One day after pre-tests, KT mechanical correction
      technique was applied to the left ankle joint (supporting leg) in the KT group,
      and tests were repeated to determine the acute effect of KT. The PN group
      participated in an 8-week balance training program (2 days/wk, 60 min/day)
      involving exercises using stable and unstable surfaces. Significant improvements
      were observed for all static and dynamic balance tests in the PN group; semi
      dynamic airplane and dynamic monopodalic-straight and transverse tests improved
      in the KT group; and only semi-dynamic airplane test scores changed significantly
      for the control group (p<0.05). Our findings suggest that with the exception of
      the semi-dynamic airplane test, both PN training and KT application were more
      effective at improving balance performance for modern dancers than modern dance
      technique classes alone.

PMID- 30204822
TI  - Musculoskeletal Health Complaints and Corresponding Risk Factors Among Music
      Students: Study Process, Analysis Strategies, and Interim Results from a
      Prospective Cohort Study.
AB  - AIM: In this prospective longitudinal study, the physical and psychological
      health status of music students is assessed at the beginning of their university
      music study and tracked over time. Analysis strategies and interim results from
      the first-year cohort, including 1-year incidences, monthly prevalences, and
      predictors of developing musculoskeletal health complaints (MHC), are presented.
      METHODS: This prospective longitudinal study is calculated to enlist a total
      sample of 370 participants, including musicians and non-musicians, over 5 years.
      Baseline measurements include a self-designed questionnaire, core strength
      endurance, hypermobility, finger-floor-distance, motor control,
      mechanosensitivity, health-related quality of life (SF36), and stress and coping
      inventory (SCI). The occurrence of MHC is based on monthly online questionnaires.
      RESULTS: The first-year subcohort enrolled 33 music students and 30 non-music
      control students. The mean monthly completion rate for the questionnaire was
      55.7+/-8.7%. At baseline, music students showed significantly more stress
      symptoms, reduced physical function!ing, and increased bodily pain compared to
      control students. The 1-year incidence of MHC was 59% for music students and 44%
      for controls. Risk factors for MHC included being a music student, previous pain,
      reduced physical functioning, stress symptoms, reduced emotional functioning, and
      mechanosensitivity. Being a music student, physical functioning, sleep duration,
      positive thinking, and general mechanosensitivity had a predictive ability of
      0.77 (ROC curve) for MHC. CONCLUSION: A total of 63 students enrolled in the
      first cohort is in line with the precalculated sample size. This prospective
      study design enables the measurement of MHC incidence and provides insight into
      mechanisms in the development of MHC among music students, including the
      interaction of physical, psychological, and psychosocial factors.

PMID- 30204823
TI  - Effects of Playing Position on Hydration Status in Collegiate Marching Band
      Musicians.
AB  - OBJECTIVE: Marching band musicians often endure prolonged daily practices in warm
      hot outdoor environments. Evaluation of hydration status by instrument position
      can shed light on health-related issues for these performers. The objective of
      this study was: a) to determine the effects of playing position on hydration
      status based on urinary biomarkers (urinary specific gravity and urinary
      osmolality) before and after marching band practice, and b) to evaluate the
      relation of hydration status with body mass change and fluid consumption for all
      playing positions. METHODS: Fifty-eight collegiate marching band players
      participated in this study, involving five playing positions: band pit (n=10),
      baritone and euphonium (n=12), snare drum (n=13), trumpet (n=12), and tuba
      (n=11). All participants performed their own routine marching band practice,
      which lasted a total of 6 hrs on 1 day. Each individual consumed ad libitum
      commercially available carbohydrate-electrolyte solution during the practice. To
      determine hydration status, urine samples were collected before and after
      practice for analysis of urinary specific gravity and urinary osmolality. Body
      weight and total fluid intake were also assessed pre- and post-exercise. RESULTS:
      There were no significant effects for playing position and time or interaction
      concerning the levels of urinary osmolality and specific gravity after practice.
      CONCLUSIONS: Our main findings suggest that hydration status may be similar among
      the different playing positions following prolonged practice in the outdoor
      environment.

PMID- 30204824
TI  - Effect of Using Ergobrass Ergonomic Supports on Postural Muscles in Trumpet,
      Trombone, and French Horn Players.
AB  - AIMS: Though ergonomic supports are widely used for many groups of instruments,
      they are rare for brass instruments, despite the instruments' considerable
      weight. Musculoskeletal injury and postural problems are common among this group,
      and so, both adult and young players are likely to benefit from supports that
      reduce the load placed on the body. This study assessed the effects on postural
      muscle activity of a recently developed range of supports (Ergobrass) that use a
      rod to transfer the weight of the instrument to a harness or to the chair or
      floor. METHODS: Twenty conservatoire students (mean age [SD], 20.9 +/- 0.5 yrs)
      of the trumpet, french horn, or trombone used the supports while playing short
      brass studies, either sitting or standing. Surface electromyography recordings
      were made from key postural muscles, and their activity levels were compared with
      and without the support. RESULTS: Statistically significant reductions (typically
      15-30%) were present in many of the muscles when using the supports, though in
      some players they were much larger. The number of muscles affected was least with
      the lightest instruments (the trumpet), with the effects mainly in the left
      deltoid and trapezius muscles. Reductions for the horn were bilateral,
      principally in biceps, pectoralis major, and deltoid; while in the trombone, they
      were confined to the left side (pectoralis major, posterior deltoid, and
      trapezius), as the right arm is in constant use to move the slide. CONCLUSIONS:
      The supports are effective in reducing postural muscle activity and may be of
      particular benefit to injured or young players.

PMID- 30204825
TI  - Challenges Faced by Woodwind Players in Malaysia While Fasting During Ramadan: A
      Case Study.
AB  - While numerous studies have investigated associations between Ramadan fasting and
      sports performance, as well as general health, little is known about the
      experiences of musicians who play while fasting. This exploratory case study
      aimed to gain a better understanding of the experiences of tertiary-level
      woodwind players who practice, rehearse, and perform while fasting. Sixteen
      undergraduate woodwind players from two Malaysian university music faculties
      completed an 11-item questionnaire, as well as a 7-day food and playing diary,
      which formed the basis for a semi-structured interview. Their experiences were
      compared with previous studies of fasting athletes. Many participants stated that
      practicing from noon to 3:00 pm was difficult due to feeling thirsty, hungry,
      tired, and exhausted, with some experiencing a dry mouth and/or lips. By 3:00 to
      6:00 pm, some had difficulty focusing and felt tired, dizzy, or lacked energy to
      practice. Many felt more comfortable playing after breaking the fast or after
      eating sahur. The majority experienced positive impacts such as increased focus
      and efficiency while practicing. This study suggests that fasting woodwind
      players would benefit from practicing in the morning and after sunset, limiting
      their practice time in the afternoon, not skipping sahur, and ensuring adequate
      hydration during sunset and sunrise.

PMID- 30204826
TI  - Cardiorespiratory Profile and Performance Demands of Elite Hip-Hop Dancers:
      Breaking and New Style.
AB  - AIMS: Dancers need to constantly maintain and develop their physiological
      capabilities to support their performances. Previously these physiological
      demands have been investigated only in traditional dance styles such as ballet
      and modern. The aim of this study was to examine the physiological demands of two
      types of hip-hop: new style and break dance. METHODS: Nine female new style
      dancers (age 20+/-6 yrs, height 163.5+/-1.4 cm, mass 55.8+/-22 kg) and 9 male
      break dancers (age 23+/-4.2 yrs, height 178.2+/-5.7 cm, mass 62.1+/-7.7 kg)
      volunteered for the study. Each subject completed a maximal graded treadmill test
      and a dance performance routine, either new style (approx 1:45-2:30 min) or
      breaking (2 min). Breathe-by-breathe gas analysis and heart rate (HR) were
      collected by a portable gas analyser, and blood lactate (BLa) was measured at the
      end of the treadmill test and each routine. RESULTS: The male breaker dancers had
      significantly higher VO2 peak than other equivalent dancers in other genres,
      whilst the female new style dancers were similar to that previously reported for
      female dancers. Performance data showed significant differences between the two
      styles for VO2, HR, and BLa (p<0.001) and for VO2 and HR relative to individual
      maximal treadmill data (p<0.05). CONCLUSION: New style is more comparable to
      other theatrical dance genres, with a lower relative mean VO2 demand, whilst
      break dance is shorter in duration, allowing a higher cardiorespiratory demand
      and generating significant levels of blood lactate. This difference is also
      reflected in the dancers' cardiorespiratory profiles.

PMID- 30204827
TI  - Combined Acquisition Method of Image and Signal Technique (CAMIST) for Assessment
      of Temporomandibular Disorders in Performing Arts Medicine.
AB  - OBJECTIVE: This pilot study investigated the morphological and functional aspects
      of an English horn player, who presented at a dental appointment with
      temporomandibular disorder (TMD), using the "combined acquisition method of image
      and signal technique" (CAMIST) in the diagnosis. METHODS: Cephalometric analysis
      was obtained after carrying out three lateral cephalograms using a standardized
      radiographic technique. The first one was taken with the teeth in the normal
      occlusion and the lips relaxed, the second with the oboe embouchure, and the last
      was performed with the English horn. To understand the pressures involved during
      the embouchure and musical performance of the English horn and oboe, a system was
      developed using force sensors placed on the double-reed mouthpiece. Finally,
      infrared imaging was used to better understand the anatomy-physiology of specific
      structures of the cranio-cervico-mandibular complex. RESULTS: Cephalometry of the
      musician showed more significant changes in the retrusion of the mandibular
      pogonion. The embouchure pressures measured during musical practice showed that
      the English horn induced a higher pressure on the lower lip than on the upper,
      while the inverse happened with the oboe. Thermography confirmed the painful site
      on the left temporomandibular joint (TMJ), and this was also observed in the
      muscle tenderness/discomfort on the right superficial masseter by the
      differential temperature of these areas. CONCLUSION: Techniques such as lateral
      teleradiography, infrared imaging, and force sensors can be useful screening
      tools with added value for the diagnosis of TMDs in performing artists.

PMID- 30204828
TI  - Effect of Fatigue on Functional Movement Screening Performance in Dancers.
AB  - OBJECTIVE: Dance is associated with a high risk of injury, with fatigue
      identified as a contributing factor. Functional movement screening (FMS) has been
      used to identify alterations in normal movement which may contribute to injury
      risk, though this test is not normally performed in a fatigued state. The aim of
      this study was to determine whether fatigue induced by the dance aerobic fitness
      test (DAFT) results in changes in FMS scores with implications for performance
      and injury risk. METHODS: Forty-one university dancers completed the FMS before
      and immediately after completion of the DAFT. Rate of perceived exertion and
      heart rate were quantified as measures of fatigue. RESULTS: Post-DAFT, the mean
      FMS composite score (15.39+/-1.86) was significantly less (p<=0.01) than the pre
      exercise score (16.83+/-1.83). Element-specific analysis revealed that the deep
      squat, non-dominant lunge, and dominant inline lunge scores were all
      significantly impaired post-DAFT (all p<=0.01). CONCLUSION: The identification of
      changes in quality of movement in a fatigued state suggests that movement
      screening should also be performed post-exercise to enhance screening for injury
      risk. The influence of dance-specific fatigue was FMS element-specific.
      Specifically, the deep squat and inline lunge were most susceptible to fatigue,
      with implications for injury risk and performance and reflective of the high
      level of neuromuscular control required.

PMID- 30204829
TI  - Making health care worth it: increasing value and awareness in performing arts
      medicine.
AB  - In recent years, across all health care disciplines, the higher quality and
      volume of specific literature on health issues pertaining to performing artists
      are allowing ever more specialised and targeted evidence-informed interventions
      to be delivered. Whether performing artists recognise the new-found knowledge as
      well as the growth in training and domain-specific expertise of certain dedicated
      health professionals is unclear. Developing and maintaining good communication
      and the establishment of trust between performing artists, educators, and health
      professionals is crucial to facilitate better management of injuries in
      performing artists.

PMID- 30204830
TI  - Comparative genomics reveals diverse capsular polysaccharide synthesis gene
      clusters in emerging Raoultella planticola.
AB  - Raoultella planticola is an emerging zoonotic pathogen that is associated with
      rare but life-threatening cases of bacteremia, biliary tract infections, and
      urinary tract infections. Moreover, increasing antimicrobial resistance in the
      organism poses a potential threat to public health. In spite of its importance as
      a human pathogen, the genome of R. planticola remains largely unexplored and
      little is known about its virulence factors. Although lipopolysaccharides has
      been detected in R. planticola and implicated in the virulence in earlier
      studies, the genetic background is unknown. Here, we report the complete genome
      and comparative analysis of the multidrug-resistant clinical isolate R.
      planticola GODA. The complete genome sequence of R. planticola GODA was sequenced
      using single-molecule real-time DNA sequencing. Comparative genomic analysis
      reveals distinct capsular polysaccharide synthesis gene clusters in R. planticola
      GODA. In addition, we found bla TEM-57 and multiple transporters related to
      multidrug resistance. The availability of genomic data in open databases of this
      emerging zoonotic pathogen, in tandem with our comparative study, provides better
      understanding of R. planticola and the basis for future work.

PMID- 30204831
TI  - Perspective: Consideration of Values When Setting Priorities in Nutrition
      Research: Guidance for Transparency.
AB  - Nutrition research can guide interventions to tackle the burden of diet-related
      diseases. Setting priorities in nutrition research, however, requires the
      engagement of various stakeholders with diverse insights. Consideration of what
      matters most in research from a scientific, social, and ethical perspective is
      therefore not an automatic process. Systematic ways to explicitly define and
      consider relevant values are largely lacking. Here, we review existing nutrition
      research priority-setting exercises, analyze how values are reported, and provide
      guidance for transparent consideration of values while setting priorities in
      nutrition research. Of the 27 (n = 22 peer-reviewed manuscripts and 5 grey
      literature documents) studies reviewed, 40.7% used a combination of different
      methods, 59.3% described the represented stakeholders, and 49.1% reported on
      follow-up activities. All priority-setting exercises were led by research groups
      based in high-income countries. Via an iterative qualitative content analysis,
      reported values were identified (n = 22 manuscripts). Three clusters of values
      (i.e., those related to impact, feasibility, and accountability) were identified.
      These values were organized in a tool to help those involved in setting research
      priorities systematically consider and report values. The tool was finalized
      through an online consultation with 7 international stakeholders. The value
      oriented tool for priority setting in nutrition research identifies and presents
      values that are already implicitly and explicitly represented in priority-setting
      exercises. It provides guidance to enable explicit deliberation on research
      priorities from an ethical perspective. In addition, it can serve as a reporting
      tool to document how value-laden choices are made during priority setting and
      help foster the accountability of stakeholders involved.

PMID- 30204832
TI  - Impact of Fractional Ablative Carbon Dioxide Laser on the Treatment of
      Rhinophyma.
AB  - Background: Rhinophyma results in nasal deformity, which may lead to significant
      distress, embarrassment, social isolation, and low self-esteem. Fractional carbon
      dioxide (CO2) laser treatment is a simple, non-invasive and outpatient procedure
      with a low complication rate that has been useful in rhinophyma treatment.
      Objectives: To assess the impact of fractional ablative CO2 laser treatment on
      self-esteem in patients with rhinophyma. Methods: Twelve patients with
      rhinophyma, between 50 and 80 years of age, received 4 monthly treatment sessions
      with a fractional ablative CO2 laser. The laser parameters were chosen based on
      the severity of the condition of each patient. Patient satisfaction was assessed
      through a study-specific questionnaire administered 1 month after treatment. Self
      esteem was assessed by the Rosenberg Self-Esteem (RSE) Scale, which was
      administered before treatment and at 1, 6, and 12 months after treatment.
      Results: A decrease in RSE scores was observed in the post-treatment period,
      indicating an improvement in self-esteem among patients. All patients were
      satisfied with the aesthetic results and would recommend the treatment to a
      friend. Conclusions: Fractional ablative CO2 laser treatment is associated with
      high levels of rhinophyma patient satisfaction and significant improvement in
      self-esteem.

PMID- 30204833
TI  - The Effects of Ambulatory Blood Pressure Monitoring on Sleep Quality in Men and
      Women with Hypertension: Dipper versus Non-Dipper and Race Differences.
AB  - Background: The non-dipping circadian blood pressure (BP) profile is associated
      with both poor sleep quality and increased cardiovascular risk. The present study
      aimed to clarify the potential confounding effects of 24-hour ambulatory blood
      pressure monitoring (ABPM) used to characterize the circadian BP profile by
      assessing its impact on sleep quality. Methods: Participants were 121 middle-aged
      men and women with untreated hypertension (age=46+/-8 years; 43% women; 45%
      African American). Subjective sleep quality was assessed using the Pittsburgh
      Sleep Quality Index (PSQI). Wrist actigraphy was used to measure sleep quality
      objectively as sleep efficiency (SE) and total sleep time (TST) on 7 consecutive
      non-ABPM days (baseline) and 3 subsequent 24-hour ABPM days. Results: Average
      ambulatory BP was 137.2+/-10.8/84.3+/-8.5 mm Hg during the day and 119.6+/
      12.4/69.5+/-9.8 mm Hg at night. Using the criterion of less than 10% dip in SBP
      to define non-dippers, there were 40 non-dippers (SBP dip=7.3+/-2.6%) and 81
      dippers (SBP dip=15.5+/-3.4%). There was no effect of time on SE or TST over non
      ABPM and ABPM days, suggesting that ABPM does not adversely affect sleep quality.
      Sleep quality was generally poorer (lower SE) in non-dippers compared to dippers
      (p=.033), but differences were independent of whether or not participants were
      undergoing 24-hour ABPM. African American race (p=.002) was also associated with
      lower SE. Conclusion: Sleep quality generally appears to be poor in men and women
      with untreated hypertension, and especially amongst African Americans.
      Importantly, for both dippers and non-dippers, we found no evidence that ABPM had
      an adverse effect on sleep quality.

PMID- 30204834
TI  - Anatomical Variations in the Course of Labial Arteries: A Literature Review.
AB  - Background: Nonsurgical lip enhancement using dermal fillers is a very popular
      procedure. The trend of enlarged lips has been popularised by media and social
      media. The lips have considerable aesthetic and functional importance, in
      addition to having a complex anatomy. Serious complications including vascular
      compromise or occlusion leading to cutaneous necrosis and blindness can occur as
      the result of lip enhancement using dermal fillers. Therefore, aesthetic
      practitioners require an in-depth understanding of the anatomy and vasculature of
      the lips and the perioral area prior to providing lip enhancement using dermal
      fillers. Objectives: This literature review aimed to summarise existing data
      describing the origin, path and depth of the SLA and ILA to help aesthetic
      practitioners in providing safer injections to the lips. Methods: A literature
      search was carried out to summarise the available data describing the origin,
      path and depth of the labial arteries. Results: Analysis of the literature
      revealed that the labial arteries display high variability with respect to path
      (distribution), presence, and location. Conclusions: Increasing the volume of
      lips through injections of dermal filler needs to be undertaken with caution, and
      awareness of the anatomical variation in artery location and path is a crucial
      concept that is mandatory knowledge when injecting the lips.

PMID- 30204835
TI  - Oncogenes expand during evolution to withstand somatic amplification.
AB  - Background: Cancer-related genes are under intense evolutionary pressure. We
      conjectured that gene size is an important determinant of amplification
      propensity for oncogenes and thus cancer susceptibility and therefore could be
      subject to natural selection. Patients and Methods: Gene information, including
      size and genomic locations, of all protein-coding genes were downloaded from
      Ensembl (release 87). Quantification of gene amplification was based on GISTIC
      scores obtained from available The Cancer Genome Atlas studies. Results:
      Oncogenes are larger in size as compared with non-cancer genes (mean size: 92.1
      kb vs 61.4 kb; p < 0.0001) in the human genome, which is contributed by both
      increased total exon size (mean size: 4.6 kb vs 3.4 kb; p < 0.0001) and higher
      intronic content (mean %: 84.8 vs 78.0; p < 0.01). Such non-random size
      distribution and intronic composition are conserved in mouse and Drosophila (all
      p-values < 0.0001). Stratification by gene age indicated that young oncogenes
      have been subject to a stronger evolutionary pressure for gene expansion than
      their non-cancer counterparts. Pan-cancer analysis demonstrated that larger
      oncogenes were amplified to a lesser extent. Tumor-suppressor genes also moved
      towards small oncogenes in the course of evolution. Conclusions: Oncogenes expand
      in size whereas tumor-suppressor genes move closer to small oncogenes in the
      course of evolution to withstand oncogenic somatic amplification. Our findings
      have shed new light on the previously unappreciated influence of gene size on
      oncogene amplification and elucidated how cancers have shaped our genome to its
      present configuration.

PMID- 30204837
TI  - A Review of the Evidence Surrounding the Effects of Breakfast Consumption on
      Mechanisms of Weight Management.
AB  - The recommendation to eat breakfast has received scrutiny due to insufficient
      causal evidence for improvements in weight management. Despite the limited number
      of randomized controlled trials examining the effects of breakfast consumption
      compared with skipping breakfast on weight loss, an increasing number of studies
      target the hormonal and behavioral mechanisms underlying weight management. This
      review provides a comprehensive examination of the intervention-based clinical
      trials that test whether breakfast consumption improves appetite control and
      satiety as well as energy expenditure compared with skipping breakfast. Several
      factors were considered when interpreting the body of evidence. These include,
      but were not limited to, the following: the composition of breakfast, with a
      specific focus on dietary protein; meal size and form; and habitual breakfast
      behaviors. The evidence within this review shows positive to neutral support for
      the inclusion of breakfast for improvements in appetite control, satiety, and
      postprandial energy expenditure. The protein content, energy content, and form of
      the meal (i.e., beverages compared with foods) are key modulating factors for
      ingestive behavior and energy expenditure mechanisms. Specifically, breakfast
      meals containing a larger amount of protein (>=30 g protein/meal) and energy
      (>=350 kcal/meal) and provided as solid foods increased the magnitude of the
      appetite and satiety response compared with breakfast skipping. Longer-term
      randomized controlled trials including the measurement of ingestive behavior and
      weight management are needed to identify the role of breakfast for health
      promotion.

PMID- 30204839
TI  - Neoadjuvant rectal score: run with the hare and hunt with the hounds.

PMID- 30204840
TI  - In vitro versus in vivo compositional landscapes of histone sequence preferences
      in eucaryotic genomes.
AB  - Motivation: Although the nucleosome occupancy along a genome can be in part
      predicted by in vitro experiments, it has been recently observed that the
      chromatin organization presents important differences in vitro with respect to in
      vivo. Such differences mainly regard the hierarchical and regular structures of
      the nucleosome fiber, whose existence has long been assumed, and in part also
      observed in vitro, but that does not apparently occur in vivo. It is also well
      known that the DNA sequence has a role in determining the nucleosome occupancy.
      Therefore, an important issue is to understand if, and to what extent, the
      structural differences in the chromatin organization between in vitro and in vivo
      have a counterpart in terms of the underlying genomic sequences. Results: We
      present the first quantitative comparison between the in vitro and in vivo
      nucleosome maps of two model organisms (S. cerevisiae and C. elegans). The
      comparison is based on the construction of weighted k-mer dictionaries. Our
      findings show that there is a good level of sequence conservation between in
      vitro and in vivo in both the two organisms, in contrast to the abovementioned
      important differences in chromatin structural organization. Moreover, our results
      provide evidence that the two organisms predispose themselves differently, in
      terms of sequence composition and both in vitro and in vivo, for the nucleosome
      occupancy. This leads to the conclusion that, although the notion of a genome
      encoding for its own nucleosome occupancy is general, the intrinsic histone k-mer
      sequence preferences tend to be species-specific. Availability and
      implementation: The files containing the dictionaries and the main results of the
      analysis are available at http://math.unipa.it/rombo/material. Supplementary
      information: Supplementary data are available at Bioinformatics online.

PMID- 30204836
TI  - Perspective: Reductionist Nutrition Research Has Meaning Only within the
      Framework of Holistic and Ethical Thinking.
AB  - Today, it seems that nutrition is in a state of great confusion, especially for
      the general public. For decades, some nutrients (e.g., cholesterol, saturated
      fats, sugars, gluten, salt) and food groups (e.g., dairy, cereals, meats) have
      been regularly denigrated. In this position paper, we hypothesize that such a
      state of confusion is mainly the result of the reductionist paradigm applied to
      nutrition research for more than a century, and by being pushed to its extreme,
      this perspective has led to accusations about some nutrients and foods. However,
      the real issue is about foods taken as a whole and therefore about their degree
      of processing, which affects both the food matrix and composition. Indeed, we eat
      whole foods, not nutrients. Therefore, the objectives of this article are to
      emphasize the need for more holistic approaches in nutrition to preserve our
      health, animal welfare, and planet. We propose to first redefine the food health
      potential on a holistic basis and then to show that reductionism and holism are
      interconnected approaches that should coexist. Then, we try to explain how
      extreme reductionism has been disconnected from reality and ethical
      considerations and has ultimately led to environmental degradation and loss of
      biodiversity, notably through very specific crops, and to an increased prevalence
      of chronic diseases. Furthermore, to address the confusion of the general public
      and to simplify nutritional messages, we propose 3 holistic golden rules based on
      scientific evidence to protect human health, animal welfare, and the environment
      (climate and biodiversity). Finally, we try to show how these 3 rules can be
      easily applied worldwide while respecting the environment, cultural traditions,
      and heritage.

PMID- 30204838
TI  - Transmission of Mobile Colistin Resistance (mcr-1) by Duodenoscope.
AB  - Background: Clinicians increasingly utilize polymyxins for treatment of serious
      infections caused by multidrug-resistant gram-negative bacteria. Emergence of
      plasmid-mediated, mobile colistin resistance genes creates potential for rapid
      spread of polymyxin resistance. We investigated the possible transmission of
      Klebsiella pneumoniae carrying mcr-1 via duodenoscope and report the first
      documented healthcare transmission of mcr-1-harboring bacteria in the United
      States. Methods: A field investigation, including screening targeted high-risk
      groups, evaluation of the duodenoscope, and genome sequencing of isolated
      organisms, was conducted. The study site included a tertiary care academic health
      center in Boston, Massachusetts, and extended to community locations in New
      England. Results: Two patients had highly related mcr-1-positive K. pneumoniae
      isolated from clinical cultures; a duodenoscope was the only identified
      epidemiological link. Screening tests for mcr-1 in 20 healthcare contacts and 2
      household contacts were negative. K. pneumoniae and E. coli were recovered from
      the duodenoscope; neither carried mcr-1. Evaluation of the duodenoscope
      identified intrusion of biomaterial under the sealed distal cap; devices were
      recalled to repair this defect. Conclusions: We identified transmission of mcr-1
      in a United States acute care hospital that likely occurred via duodenoscope
      despite no identifiable breaches in reprocessing or infection control practices.
      Duodenoscope design flaws leading to transmission of multidrug-resistant
      organsisms persist despite recent initiatives to improve device safety. Reliable
      detection of colistin resistance is currently challenging for clinical
      laboratories, particularly given the absence of an FDA-cleared test; improved
      clinical laboratory capacity for colistin susceptibility testing is needed to
      prevent the spread of mcr-carrying bacteria in healthcare settings.

PMID- 30204841
TI  - The Influence of Side Effect Information Framing on Nocebo Effects.
AB  - Background: One contributing factor to the development of nocebo effects is
      information provided about possible side effects. However, nondisclosure of
      information can be problematic. Purpose: We assessed whether positively framed
      side effect information (highlighting likelihood of not experiencing side
      effects) can reduce nocebo effects compared to negatively framed information
      (highlighting likelihood of experiencing side effects). Methods: One hundred
      twelve participants took part in research ostensibly assessing the influence of
      benzodiazepines (actually sham capsules) on anxiety. Participants were randomized
      to receive a sham capsule with positively or negatively framed information about
      four side effects, or a no-treatment control condition. Side effect expectations
      were assessed after information provision. Framed side effects and other
      unmentioned symptoms were assessed during the session and 24-hr follow-up.
      Results: Nocebo effects occurred in symptoms presented as side effects
      (regardless of framing) during the study session and follow-up (ps < .003). At
      follow-up, there was also a nocebo effect in other unmentioned symptoms (p =
      .018). Positive framing reduced side effect symptoms compared with negative
      framing during the study session (p = .037), but this effect was no longer
      present at follow-up (p = .53). Side effect expectations did not differ between
      the framing conditions (p = .14). Conclusions: Positive framing reduced side
      effects short-term, but not at follow-up. Expectations did not differ between
      negative and positive framing. Nocebo effects appeared to generalize to other
      unmentioned symptoms over a 24-hr period. Further research is needed to determine
      whether the initial impact of positive framing can be maintained over time.

PMID- 30204842
TI  - Matricellular protein periostin promotes colitis-associated colon tumorigenesis
      in mice.
AB  - Periostin is expressed in inflamed colonic mucosa and colon cancer tissue;
      however, its role in the development of colitis-associated colon cancer (CAC)
      remains unclear. Wild type and periostin-deficient (Postn-/-) mice were given a
      single intraperitoneal injection of azoxymethane (AOM) at 12.5 mg/kg on Day 0.
      Seven days later, 2% dextran sulfate sodium (DSS) was administered via drinking
      water for 5 days, followed by free water consumption for 16 days. This cycle was
      repeated 3 times. In vitro assays were performed using COLO205 and HCT116 cells.
      Small interfering RNA was used to inhibit Postn gene translation. Periostin
      expression was determined using colon samples from patients with CAC. Postn-/-
      mice exhibited lower tumor burden compared with wild type mice. Exposure to
      AOM/DSS resulted in extensive epithelial apoptosis in Postn-/- mice compared to
      that in wild type mice. In addition, immunoreactivity for IKK, beta-catenin, and
      COX2 was markedly reduced in Postn-/- mice. Expression of IL-1beta and TNF-alpha
      significantly decreased whereas that of IL-10 and TGF-beta increased in
      peritoneal macrophages isolated from Postn-/- mice. Silencing of the Postn gene
      resulted in reduced cell viability, which was associated with caspase-3
      activation, and this was reversed by treatment with recombinant periostin.
      Knockdown of Postn downregulated BcL-2, cIAP1, cFLIP-L, VEGF, axin2, and cyclin
      D1 and upregulated BAK expression. Periostin expression was significantly
      increased in patients with CAC. Periostin aggravates CAC development, which
      suggests that periostin is a potential therapeutic target for the prevention of
      CAC in patients with inflammatory bowel disease.

PMID- 30204843
TI  - Outbreak of Hypervirulent Multi-Drug Resistant Klebsiella variicola causing high
      mortality in neonates in Bangladesh.
AB  - We report an outbreak by MDR K. variicola clone (ST771) in a Bangladeshi neonatal
      unit from October, 2016 to January, 2017, associated with high mortality (54.5%).
      During the outbreak, K. variicola ST771 acquired MDR plasmid harbouring blaNDM-1,
      linked to high exposure to ceftriaxone and amikacin in the NICU of DMCH.

PMID- 30204844
TI  - Estimation of direct healthcare costs of fungal diseases in the United States.
AB  - Background: Fungal diseases range from relatively minor superficial and mucosal
      infections to severe, life-threatening systemic infections. Delayed diagnosis and
      treatment can lead to poor patient outcomes and high medical costs. The overall
      burden of fungal diseases in the United States is challenging to quantify because
      they are likely substantially underdiagnosed. Methods: To estimate total national
      direct medical costs associated with fungal diseases from a healthcare payer
      perspective, we used insurance claims data from the Truven Health MarketScan(r)
      2014 Research Databases, combined with hospital discharge data from the 2014
      Healthcare Cost and Utilization Project National Inpatient Sample and outpatient
      visit data from the 2005-2014 National Ambulatory Medical Care Survey and the
      National Hospital Ambulatory Medical Care Survey. All costs were adjusted to 2017
      dollars. Results: We estimate that fungal diseases cost more than $7.2 billion in
      2017, including $4.5 billion from 75,055 hospitalizations and $2.6 billion from
      8,993,230 outpatient visits. Hospitalizations for Candida infections (n=26,735,
      total cost $1.4 billion) and Aspergillus infections (n=14,820, total cost $1.2
      billion) accounted for the highest total hospitalization costs of any disease.
      Over half of outpatient visits were for dermatophyte infections (4,981,444
      visits, total cost $802 million), and 3,639,037 visits occurred for non-invasive
      candidiasis (total cost $1.6 billion). Conclusions: Fungal diseases impose a
      considerable economic burden on the healthcare system. Our results likely under
      estimate their true costs because they are underdiagnosed. More comprehensive
      estimates of the public health impact of these diseases are needed to improve
      their recognition, prevention, diagnosis, and treatment.

PMID- 30204845
TI  - A Centralised multidisciplinary clinic approach for germ cell tumours.

PMID- 30204846
TI  - New Alcohol Biomarkers. New challenges.

PMID- 30204847
TI  - KeggExp: a web server for visual integration of KEGG pathways and expression
      profile data.
AB  - Summary: Effective visualization is important for knowledge discovery when
      analysing expression profile data. However, existing tools for visually
      integrating expression profile data with KEGG pathway maps lack extensive
      interactive visualization operations. KeggExp simultaneously presents the pathway
      map of one pathway, dendrogram & heatmap of the genes in the pathway, and scatter
      map of one gene; and also provides interactive operations for highlighting
      specific genes on the pathway map, including differentially-expressed genes, co
      expressed genes selected from the heatmap, and user-input genes. With KeggExp,
      researchers, including those without programming skills, can take advantage of
      its interactive operations to determine key genes or pathways when analysing
      expression profile data. Availability and Implementation: Freely available at
      http://www.fgvis.com/expressvis/KeggExp/. Language: JavaScript, python;
      Libraries: D3.js, Rxjs, Angular, Django, Django rest frame work, Scipy.
      Supplementary information: Supplementary data are available at Bioinformatics
      online.

PMID- 30204848
TI  - emeraLD: rapid linkage disequilibrium estimation with massive datasets.
AB  - Summary: Estimating linkage disequilibrium (LD) is essential for a wide range of
      summary statistics-based association methods for genome-wide association studies.
      Large genetic datasets, e.g. the TOPMed WGS project and UK Biobank, enable more
      accurate and comprehensive LD estimates, but increase the computational burden of
      LD estimation. Here, we describe emeraLD (Efficient Methods for Estimation and
      Random Access of LD), a computational tool that leverages sparsity and haplotype
      structure to estimate LD up to 2 orders of magnitude faster than current tools.
      Availability and implementation: emeraLD is implemented in C++, and is open
      source under GPLv3. Source code and documentation are freely available at
      http://github.com/statgen/emeraLD. Supplementary information: Supplementary data
      are available at Bioinformatics online.

PMID- 30204849
TI  - Individual Variation in PROP Status, Fungiform Papillae Density, and
      Responsiveness to Taste Stimuli in a Large Population Sample.
AB  - Despite considerable research investigating the role of 6-n-propylthiouracil
      bitterness perception and variation of fungiform papillae density in food
      perception, this relationship remains controversial as well as the association
      between the 2 phenotypes. Data from 1119 subjects (38.6% male; 18-60 years)
      enrolled in the Italian Taste project were analyzed. Responsiveness to the
      bitterness of 6-n-propylthiouracil was assessed on the general Labeled Magnitude
      Scale. Fungiform papillae density was determined from manual counting on digital
      images of the tongue. Solutions of tastes, astringent, and pungent sensations
      were prepared to be moderate/strong on a general Labeled Magnitude Scale. Four
      foods had tastants added to produce 4 variations in target sensations from weak
      to strong (pear juice: citric acid, sourness; chocolate pudding: sucrose,
      sweetness; bean puree: sodium chloride, saltiness; and tomato juice: capsaicin,
      pungency). Women gave ratings to 6-n-propylthiouracil and showed fungiform
      papillae density that was significantly higher than men. Both phenotype markers
      significantly decreased with age. No significant correlations were found between
      6-n-propylthiouracil ratings and fungiform papillae density. Fungiform papillae
      density variation does not affect perceived intensity of solutions.
      Responsiveness to 6-n-propylthiouracil positively correlated to perceived
      intensity of most stimuli in solution. A significant effect of fungiform papillae
      density on perceived intensity of target sensation in foods was found in a few
      cases. Responsiveness to 6-n-propylthiouracil positively affected all taste
      intensities in subjects with low fungiform papillae density whereas there were no
      significant effects of 6-n-propylthiouracil in those with high fungiform papillae
      density. These data highlight a complex interplay between 6-n-propylthiouracil
      status and fungiform papillae density and the need of a critical reconsideration
      of their role in food perception and acceptability.

PMID- 30204850
TI  - Characteristics of Large Mumps Outbreaks in the United States during July 2010
      December 2015.
AB  - Background: Mumps is an acute viral illness that classically presents with
      parotitis. Although the United States experienced a 99% reduction in mumps cases
      following implementation of the 2-dose vaccination program in 1989, mumps has
      resurged in the past 10 years. Methods: We assessed the epidemiological
      characteristics of mumps outbreaks with >=20 cases reported in the United States
      electronically through the National Notifiable Diseases Surveillance System and
      from supplemental outbreak data through direct communications with jurisdictions
      from July 2010 through December 2015. Mumps cases were defined using the 2012
      Council of State and Territorial Epidemiologists case definition. Results: Twenty
      three outbreaks with 20-485 cases/outbreak were reported in 18 jurisdictions. The
      duration of outbreaks ranged from 1.5-8.5 months (median: 3 months). All
      outbreaks involved close-contact settings; 18 (78%) involved universities, 16
      (70%) occurred primarily among young adults (median: 18-24 years of age), and 9
      (39%) occurred in highly vaccinated populations (2 dose measles-mumps-rubella
      [MMR] vaccine coverage >85%). Conclusions: During 2010-2015, multiple mumps
      outbreaks among highly vaccinated populations in close-contact settings occurred.
      Most cases occurred among vaccinated young adults, suggesting waning immunity
      played a role. Further evaluation of risk factors associated with these outbreaks
      is warranted.

PMID- 30204852
TI  - What's old is new again: the re-emergence of yellow fever in Brazil and vaccine
      shortages.
AB  - Yellow fever outbreaks have continued to occur and caused infection and deaths in
      travelers from non-endemic regions. Yellow fever vaccine has proven effective,
      but vaccination decision requires balancing its benefits with risks. Of concern
      is the continued vaccine shortage worldwide including the YF-VAX(r) stockout in
      North America that has presented many challenges.

PMID- 30204851
TI  - Carriage of extended-spectrum beta-lactamase-producing Enterobacteriaceae and the
      risk of surgical site infection after colorectal surgery: a prospective cohort
      study.
AB  - Background: Antibiotic prophylaxis covering enteric pathogens is essential in
      preventing surgical site infection (SSI) after colorectal surgery. Current
      prophylaxis regimens do not cover extended-spectrum beta lactamase-producing
      Enterobacteriaceae (ESBL-PE). We aimed to determine whether the risk of SSI
      following colorectal surgery is higher in ESBL-PE carriers than in non-carriers.
      Methods: We conducted a prospective cohort study of patients undergoing elective
      colorectal surgery in three hospitals in Israel, Switzerland, and Serbia between
      2012-2017. We included patients who were 18 and older, were screened for ESBL-PE
      carriage before surgery, received routine prophylaxis with a cephalosporin plus
      metronidazole, and did not have an infection at the time of surgery. The exposed
      group was all ESBL-PE positive patients. The unexposed group was a random sample
      of ESBL-PE negative patients. We collected data on patient and surgery
      characteristics and SSI outcomes. We fit logistic mixed effects models with study
      site as a random effect. Results: A total of 3600 patients were screened for ESBL
      PE; 13.8% were carriers (E.coli, 81.3%, other ESBL-PE, 18.7 %). We analyzed 222
      ESBL-PE carriers and 440 non-carriers. SSI occurred in 55 carriers (24.8%) and 49
      non-carriers (11.1%, P<0.001). In multivariable analysis, ESBL-PE carriage more
      than doubled the risk of SSI (OR= 2.36, 95% CI: 1.50-3.71). Carriers had higher
      risk of deep SSI (OR= 2.25 95% CI: 1.27 - 3.99). SSI caused by ESBL-PE occurred
      in 7.2% of carriers and 1.6% of non-carriers (OR= 4.23, 95% CI: 1.70-10.56).
      Conclusion: ESBL-PE carriers who receive cephalosporin-based prophylaxis are at
      increased risk of SSI following colorectal surgery.

PMID- 30204853
TI  - Challenges of vaccine effectiveness and waning studies.

PMID- 30204854
TI  - Influenza Vaccine Effectiveness in the United States during the 2016-2017 Season.
AB  - Background: In recent influenza seasons, the effectiveness of inactivated
      influenza vaccines against circulating A(H3N2) virus has been lower than against
      A(H1N1)pdm09 and B viruses, even when circulating viruses remained antigenically
      similar to vaccine components. Methods: During the 2016-2017 influenza season,
      vaccine effectiveness (VE) across age groups and vaccine types was examined among
      outpatients with acute respiratory illness at 5 US sites using a test-negative
      design that compared the odds of vaccination among reverse transcription
      polymerase chain reaction-confirmed influenza positives and negatives. Results:
      Among 7083 enrollees, 1342 (19%) tested positive for influenza A(H3N2), 648 (9%)
      were positive for influenza B (including B/Yamagata, n = 577) and 5040(71%) were
      influenza negative. Vaccine effectiveness was 40% (95% confidence interval [CI],
      32% to 46%) against any influenza virus, 33% (95%CI, 23% to 41%) against
      influenza A(H3N2) viruses and 53% (95%CI, 43% to 61%) against influenza B
      viruses. Conclusions: The 2016-2017 influenza vaccines provided moderate
      protection against any influenza among outpatients, but were less protective
      against influenza A(H3N2) viruses than B viruses. Approaches to improving
      effectiveness against A(H3N2) viruses are needed.

PMID- 30204855
TI  - Intra-season Waning of Influenza Vaccine Effectiveness.
AB  - Background: In the United States it is recommended that health care providers
      offer influenza vaccination by October, if possible. However, if the vaccine's
      effectiveness soon begins to wane, the optimal time for vaccination may be
      somewhat later. We examined whether the effectiveness of influenza vaccine wanes
      during the influenza season with increasing time since vaccination. Methods: We
      identified persons who were vaccinated with inactivated influenza vaccine from
      September 1, 2010 to March 31, 2017 and who were subsequently tested for
      influenza and respiratory syncytial virus (RSV) by a polymerase chain reaction
      test. Test-confirmed influenza was the primary outcome and days-since-vaccination
      was the predictor of interest in conditional logistic regression. Models were
      adjusted for age and conditioned on calendar day and geographic area. RSV was
      used as a negative control outcome. Results: Compared with persons vaccinated 14
      to 41 days prior to being tested, persons vaccinated 42 to 69 days prior to being
      tested had 1.32 (95% Confidence Interval (CI): 1.11 to 1.55) times the odds of
      testing positive for any influenza. The odds ratio (OR) increased in linear
      fashion by approximately 16% for each additional 28 days since vaccination; the
      OR was 2.06 (95% CI: 1.69 to 2.51) for persons vaccinated 154 or more days prior
      to being tested. No evidence of waning was found for RSV. Conclusions: Our
      results suggest that effectiveness of inactivated influenza vaccine wanes during
      the course of a single season. These results may lead to reconsideration of the
      optimal timing of seasonal influenza vaccination.

PMID- 30204856
TI  - Reply to Lupo, et al.

PMID- 30204857
TI  - Utility of Epstein-Barr Virus biomarkers in HIV-related lymphomas in the modern
      combined antiretroviral therapy era.

PMID- 30204858
TI  - Association between process performance measures and 1-year mortality among
      patients with incident heart failure: a Danish nationwide study.
AB  - Aims: To examine the association between fulfilment of performance measures
      supported by clinical guidelines recommendations and 1-year mortality among
      patients with incident heart failure (HF) in Denmark. Methods and results: A
      nationwide population-based follow-up study based on the Danish Heart Failure
      Registry. All Danish hospital departments caring for patients with HF. We
      identified 24,308 in-and outpatients diagnosed with HF from 2003 to 2010. Quality
      of care was defined as receiving the guideline recommended processes of care: use
      of echocardiography, New-York-Heart-Association -classification, treatment with
      angiotensin-converting-enzyme inhibitors/angiotensin-II-receptor blocker,
      betablockers, physical training and patient education. Main outcome measure: 1
      year mortality. We used multiple imputation and multivariable Cox Proportional
      Hazard Regression to compute Hazard Ratios (HRs) for 1-year mortality adjusted
      for potential confounding factors. Within 1 year, 17.1% of the patients died and
      the adjusted HRs ranged from 0.61 (95% Confidence Interval ((CI) 0.55-0.67)) for
      patient education to 0.99 (95% CI 0.90-1.10) for betablocker therapy. The
      association between meeting more performance measures and 1-year mortality
      appeared to follow a dose-response pattern: Using 0-25% of fulfilled measures as
      reference, patients who fulfilled 76- 100% of the performance measures had an
      adjusted HR of 0.43 (95% CI 0.38-0.48), while the adjusted HR was 0.96 (95% CI
      0.86-1.07) for patients who fulfilled between 26-50% of the performance measures.
      Conclusion: Meeting process performance measures, which reflect care in
      concordance with clinical guideline recommendations, was associated with
      substantially lower 1-year mortality among patients with incident HF.

PMID- 30204859
TI  - Efficacy of Nutritional Intervention in Elderly After Hip Fracture: A Multicenter
      Randomized Controlled Trial.
AB  - Background: Malnutrition after hip fracture is associated with increased
      rehabilitation time, complications, and mortality. We assessed the effect of
      intensive 3 month nutritional intervention in elderly after hip fracture on
      length of stay (LOS). Methods: Open-label, randomized controlled trial. Exclusion
      criteria: age < 55 years, bone disease, life expectancy < 1 year, bedridden,
      using oral nutritional supplements (ONS) before hospitalization, and cognitive
      impairment. Intervention: weekly dietetic consultation, energy-protein-enriched
      diet, and ONS (400 mL per day) for 3 months. Control: usual nutritional care.
      Primary outcome: total LOS in hospital and rehabilitation clinic, including
      readmissions over 6 months (Cox regression adjusted for confounders); hazard
      ratio (HR) < 1.0 reflects longer LOS in the intervention group. Secondary
      outcomes: nutritional and functional status, cognition, quality of life,
      postoperative complications (6 months); subsequent fractures and all-cause
      mortality (1 and 5 years). Effect modification by baseline nutritional status was
      also tested. Results: One hundred fifty-two patients were randomized (73
      intervention, 79 control). Median total LOS was 34.0 days (range 4-185 days) in
      the intervention group versus control 35.5 days (3-183 days; plogrank = .80;
      adjusted hazard ratio (adjHR): 0.98; 95% CI: 0.68-1.41). Hospital LOS: 12.0 days
      (4-56 days) versus 11.0 days (3-115 days; p = .19; adjHR: 0.75; 95% CI: 0.53
      1.06) and LOS in rehabilitation clinics: 19.5 days (0-174 days) versus 18.5 days
      (0-168 days; p = .82; adjHR: 1.04; 95% CI: 0.73-1.48). The intervention improved
      nutritional intake/status at 3, but not at 6 months, and did not affect any other
      outcome. No difference in intervention effect between malnourished and well
      nourished patients was found. Conclusions: Intensive nutritional intervention
      after hip fracture improved nutritional intake and status, but not LOS or
      clinical outcomes. Paradigms underlying nutritional intervention in elderly after
      hip fracture may have to be reconsidered.

PMID- 30204861
TI  - Identity and role of the non-conserved acid/base catalytic residue in the GH29
      fucosidase from the spider Nephilingis cruentata.
AB  - alpha-l-Fucosidases are widely occurring enzymes that remove fucose residues from
      N- and O-fucosylated glycoproteins. Comparison of amino acid sequences of
      fucosidases reveals that although the nucleophile is conserved among all alpha-l
      fucosidases, the position of the acid/base residue is quite variable. Although
      several site-directed mutation studies have previously been performed on
      bacterial fucosidases, the only eukaryotic fucosidase so studied was the human
      fucosidase. Recent alignments indicate that human and Arthropoda alpha-l
      fucosidases share at least 50% identity and the acid/base residue seems to be
      conserved among them suggesting a common acid/base residue in Metazoa. Here we
      describe the cloning and expression in Pichia pastoris of a very active alpha-l
      fucosidase from the spider Nephilingis cruentata (NcFuc) with a Km value for
      pNPFuc of 0.4 mM. NcFuc hydrolyzed fucoidan, 2'fucosyllactose and also lacto-N
      difucohexaose II. Mutants modified at the conserved residues D214N, E209A, E59A
      were expressed and characterized. The 500-fold lower kcat of D214N than the wild
      type was consistent with a role in catalysis, as was the 8000-fold lower kcat
      value of E59A. This was supported by the 57-fold increase in the kcat of E59A
      upon addition of azide. A complex pH/rate profile was seen for the wild-type and
      mutant forms of NcFuc, similar to those measured previously for the Sulfolobus
      fucosidase. The non-conservative catalytic structure and distinct active site
      organization reinforce the necessity of structural studies of new fucosidases.

PMID- 30204860
TI  - Turning Vice into Virtue: Using Batch-Effects to Detect Errors in Large Genomic
      Data Sets.
AB  - It is often unavoidable to combine data from different sequencing centers or
      sequencing platforms when compiling data sets with a large number of individuals.
      However, the different data are likely to contain specific systematic errors that
      will appear as SNPs. Here, we devise a method to detect systematic errors in
      combined data sets. To measure quality differences between individual genomes, we
      study pairs of variants that reside on different chromosomes and co-occur in
      individuals. The abundance of these pairs of variants in different genomes is
      then used to detect systematic errors due to batch effects. Applying our method
      to the 1000 Genomes data set, we find that coding regions are enriched for
      errors, where ~1% of the higher frequency variants are predicted to be erroneous,
      whereas errors outside of coding regions are much rarer (<0.001%). As expected,
      predicted errors are found less often than other variants in a data set that was
      generated with a different sequencing technology, indicating that many of the
      candidates are indeed errors. However, predicted 1000 Genomes errors are also
      found in other large data sets; our observation is thus not specific to the 1000
      Genomes data set. Our results show that batch effects can be turned into a virtue
      by using the resulting variation in large scale data sets to detect systematic
      errors.

PMID- 30204863
TI  - Mortality after the death of a parent in adulthood: a register-based comparison
      of two ethno-linguistic groups.
AB  - Background: Most research on parental bereavement and health have analysed health
      consequences of parental loss in childhood, while collateral health in adulthood
      has been less studied. Methods: Using register-based population data from
      Finland, we analyse adult offspring aged 18-50 years with discrete-time hazard
      models that adjust for offspring and parental socioeconomic and demographic
      characteristics. In focus are adult children whose parents were alive and lived
      together at the beginning of the observation period. We compare two culturally
      distinct but otherwise similar ethno-linguistic groups, Finnish speakers and
      Swedish speakers. Results: The results suggest that bereaved men have an
      approximately 30% higher death risk than non-bereaved men, while there is
      practically no difference in women. Associations between parental and child
      deaths are, as expected, stronger for concordant causes of death than for
      discordant causes of death. However, some associations for discordant causes of
      death remain, which may indicate causality. Among Swedish speakers, who have
      notably higher family stability than Finnish speakers, the death of one or both
      parents shows a stronger association with own mortality. Conclusions: The
      estimated associations found are generally larger than in the neighbouring
      country Sweden, which may be due to a stronger obedience to traditional family
      values and patriarchal family roles in Finland. These findings suggest that the
      association between parental death and mortality in adult offspring may depend on
      the societal context as well as on cultural practices. These factors should be
      increasingly acknowledged in future studies on collateral health.

PMID- 30204862
TI  - Plastin 3 influences bone homeostasis through regulation of osteoclast activity.
AB  - Over 200 million people suffer from osteoporosis worldwide, one third of which
      will develop osteoporotic bone fractures. Unfortunately, no effective cure
      exists. Mutations in plastin 3 (PLS3), an F-actin binding and bundling protein,
      cause X-linked primary osteoporosis in men and predisposition to osteoporosis in
      postmenopausal women. Moreover, the strongest association so far for osteoporosis
      in elderly women after menopause was connected to a rare SNP in PLS3, indicating
      a possible role of PLS3 in complex osteoporosis as well. Interestingly, 5% of the
      general population are overexpressing PLS3, with yet unknown consequences. Here,
      we studied ubiquitous Pls3 knockout and PLS3 overexpression in mice and
      demonstrate that both conditions influence bone remodeling and structure: while
      Pls3 knockout mice exhibit osteoporosis, PLS3 overexpressing mice show thickening
      of cortical bone and increased bone strength. We show that unbalanced PLS3 levels
      affect osteoclast development and function, by misregulating the NFkappaB
      pathway. We found upregulation of RELA (NFkappaB subunit p65) in PLS3
      overexpressing mice-known to stimulate osteoclastogenesis-but strikingly reduced
      osteoclast resorption. We identify NFkappaB repressing factor (NKRF) as a novel
      PLS3 interactor, which increasingly translocates to the nucleus when PLS3 is
      overexpressed. We show that NKRF binds to the NFkappaB downstream target and
      master regulator of osteoclastogenesis nuclear factor of activated T cells 1
      (Nfatc1), thereby reducing its transcription and suppressing osteoclast function.
      We found the opposite in Pls3 knockout osteoclasts, where decreased nuclear NKRF
      augmented Nfatc1 transcription, causing osteoporosis. Regulation of
      osteoclastogenesis and bone remodeling via the PLS3-NKRF-NFkappaB-NFATC1 axis
      unveils a novel possibility to counteract osteoporosis.

PMID- 30204864
TI  - Second-Look Endoscopy in Hospitalized Severe Ulcerative Colitis: A Retrospective
      Cohort Study.
AB  - Background: Acute severe ulcerative colitis (ASUC) is a serious complication of
      ulcerative colitis (UC). Management of partial responders to steroids or rescue
      therapy remains challenging. Whether there is a role for re-look sigmoidoscopic
      evaluation in disease management is unknown. Methods: Our study cohort consisted
      of patients who underwent 2 sigmoidoscopic procedures during the same index
      hospitalization for ASUC at our center. Reasons for repeat endoscopic evaluation
      and endoscopic and histologic severity of inflammation during both procedures
      were noted. Multivariable regression models were performed to identify predictors
      of improvement at the second endoscopic assessment and to determine the
      independent effect of such an improvement on in-hospital colectomy and at 3, 6,
      and 12 months. Results: Our study included 49 patients (mean age, 42 years; 52%
      women). Just under one-third of patients (30%) were noted to have improved
      endoscopic appearance at the second sigmoidoscopy, at a median of 9 days after
      initial exam. None of the patients who had improvement on the second endoscopy
      underwent in-hospital colectomy, compared with 46% of those with worsening or
      persistent disease (P = 0.002). Similar differences in the improved group
      persisted at 3 months (P = 0.007) and 6 months (P = 0.027). Histologic severity
      at the first endoscopy was associated with increased risk of colectomy in
      hospital (odds ratio, 3.8; 95% confidence interval, 1.02-14.21) and at 3 and 6
      months. Conclusions: After a median interval of 9 days, endoscopic improvement
      was noted in 30% of patients with ASUC undergoing a second sigmoidoscopy, which
      predicted lower rates of colectomy in-hospital and at 3 and 6 months.

PMID- 30204865
TI  - Effectiveness of adherence to recommended clinical examinations of diabetic
      patients in preventing diabetes-related hospitalizations.
AB  - Objective: To validate a set of indicators for quality of diabetes care through
      their relationship with measurable clinical outcomes. Design: A retrospective
      cohort study was carried out from 2010 to 2015. Setting: Population-based study.
      Data were retrieved from healthcare utilization databases of three Italian
      regions (Lombardy, Emilia Romagna and Lazio) on the whole covering 20 million
      citizens. Participants: The 77 285 individuals who were newly taken in care for
      diabetes during 2010 entered into the cohort. Interventions: Exposure to selected
      clinical recommendations (i.e. periodic controls for glycated hemoglobin, lipid
      profile, urine albumin excretion, serum creatinine and dilated eye exams) was
      recorded. Main outcomes measures: A composite outcome was employed taking into
      account hospitalizations for brief-term diabetes complications, uncontrolled
      diabetes, long-term vascular outcomes and no traumatic lower limb amputation. A
      multivariable proportional hazards model was fitted to estimate hazard ratio, and
      95% confidence intervals (CI), for the exposure-outcome association. Results:
      Among the newly taken in care patients with diabetes, those who adhered to almost
      none (0 or 1), just some (2 or 3) or almost all (4 or 5) recommendations during
      the first year after diagnosis were 44%, 36% and 20%, respectively. Compared
      patients who adhered to almost none recommendation, significant risk reductions
      of 16% (95% CI, 6-24%) and 20% (7-28%) were observed for those who adhered to
      just some and almost all recommendations, respectively. Conclusions: Tight
      control of patients with diabetes through regular clinical examinations must to
      be considered the cornerstone of national guidance, national audits and quality
      improvement incentives schemes.

PMID- 30204867
TI  - Examining gender health inequalities in Europe using a Synthetic Health
      Indicator: the role of family policies.
AB  - Background: Family policies have been shown to affect men's and women's health
      throughout the European Union, though particularly in the case of women. This
      paper seeks to analyze this effect by creating two Synthetic Health Indicators
      (SHIs) differentiated by gender applying the P2 distance method. We also aim to
      compare the results obtained by means of our SHI and the Self-rated health (SRH)
      indicator, as it is the most common indicator used to approach individuals'
      health. Methods: The 2012 European Quality of Life Survey was used to construct
      the SHI. Dimensions such as physical health, mental health, psychosocial
      resources, the capacity of health services and community health status were
      included in our SHI. All proved to be relevant when measuring individuals'
      health. Results: Gender health inequalities differed depending on the indicator
      used in each European country. When considering family policy, we found
      significant gender health gaps that favoured men in traditional countries,
      regardless of the indicator used (SHI or SRH). Moreover, with our SHI we found
      significant gender health inequalities in market-oriented and dual-earner
      countries that were not revealed by the SRH indicator, highlighting the fact that
      current equality policies are necessary but insufficient to overcome the gender
      health gap. Conclusions: The SHI was more sensitive to gender differences and
      evidenced certain advantages compared to the SRH. The SHI includes a wide range
      of variables that incorporated large amounts of fresh information, allowing men
      and women to have a personalized design of their own health.

PMID- 30204868
TI  - Insulin-like peptide 3 (INSL3) is a major regulator of female reproductive
      physiology.
AB  - BACKGROUND: Insulin-like peptide 3 (INSL3) is a member of the relaxin family of
      neohormones which has evolved to address specifically mammalian aspects of
      reproduction related to viviparity and internal fertilization. It was originally
      identified as a major product of testicular Leydig cells and has proved to be an
      important biomarker of Leydig cell functional capacity. However, INSL3 is also
      produced by theca interna cells of growing antral follicles and is secreted into
      the bloodstream in phases corresponding to the number and health of the
      follicles. Moreover, gene silencing experiments have shown that INSL3 is
      essentially required for androstenedione synthesis, which is the major steroid
      precursor for the granulosa cells of antral follicles to produce oestrogens.
      Knockout studies in mice confirm that loss of INSL3 or its receptor in females
      leads to partial infertility, with reduced follicle numbers, ovulations and
      litter size. Circulating INSL3 concentration corresponds to the reproductive
      lifespan, beginning with puberty and declining at the menopause, and thus may
      contribute to the physiology of other organ systems, particularly those relevant
      for hormone replacement strategies. SEARCH METHODS: A literature review was
      carried out by exhaustive searching of literature databases (PubMed and Google
      Scholar) with the search terms INSL3, RLF, Ley-IL and RXFP2. OBJECTIVE AND
      RATIONALE: We present the first comprehensive review of INSL3 and its specific
      receptor RXFP2, and their roles in the context of female reproductive physiology.
      Moreover, we highlight the potential involvement of INSL3 in female reproductive
      pathology, such as PCOS, its clinical application as a valuable biomarker of
      reproductive processes, and its potential for therapeutic interventions.
      OUTCOMES: In the female mammal, INSL3 is largely produced by the theca interna
      cells of growing antral follicles during the follicular phase of the menstrual
      (oestrous) cycle. Within the follicle, INSL3 acts via its G-protein-coupled
      receptor, RXFP2, in an autocrine/paracrine manner to orchestrate and drive the
      production of the major steroid precursor androstenedione and its conversion by
      granulosa cells into oestrogens. These in turn create a positive feedback loop
      promoting the expression of more theca cell INSL3. This is countered by the
      follicular production of bone morphogenetic proteins and by the LH surge. Thus,
      the activity of the theca cell INSL3-RXFP2 system effectively determines the
      production of estradiol within an antral follicle through the follicular phase.
      INSL3 is also secreted into the circulation where it acts as a valuable biomarker
      to monitor the growth of antral follicles; it is consequently increased in PCOS
      and decreased in women with premature ovarian failure (POF). As an endocrine
      factor, INSL3 may also influence bone metabolism and kidney function.
      Additionally, INSL3 or its analogues may prove valuable as an adjunct in hormone
      replacement therapy or to monitor or influence IVF protocols. WIDER IMPLICATIONS:
      The INSL3-RXFP2 system represents a new regulatory pathway essential for the
      proper functioning of growing antral follicles. We still know very little about
      its involvement in pathologies such as PCOS or POF, and its role as a new
      biomarker of female function needs to be explored more widely to improve
      diagnosis and treatment of ovarian dysfunction. We need to examine how INSL3
      might be used to improve IVF protocols and outcomes. Opportunities should also be
      investigated in regard to the systemic application of INSL3 as a rejuvenant
      therapy, with positive effects on bone or kidney function, and possibly also for
      fertility regulation. Most research to date has involved animal models; this now
      needs to be extended to include more human studies.

PMID- 30204870
TI  - Galectin-3 binds selectively to the terminal, non-reducing end of beta(1->4)
      galactans, with overall affinity increasing with chain length.
AB  - Galactans are linear polysaccharides of beta(1->4)-linked galactose residues.
      Although they can antagonize galectin function, the nature of their binding to
      galectins needs to be better defined to develop them as drugs. Here, we
      investigated interactions between galectin-3 (Gal-3) and a series of galactans
      ranging in weight average molecular weight from 670 to 7550 Da. 15N-1H HSQC NMR
      studies with 15N-labeled Gal-3 carbohydrate recognition domain (CRD) indicate
      that each of these galactans interacts primarily with residues in beta-strands 4,
      5 and 6 on the canonical, beta-galactoside sugar binding S-face. Although these
      galactans also bind to full length Gal-3 (CRD plus N-terminal tail) to the same
      extent, it appears that binding to the S-face attenuates interactions between the
      CRD F-face and N-terminal tail, making interpretation of site-specific binding
      unclear. Following assignment of galactan 13C and 1H resonances using HSQC, HMBC
      and TOCSY experiments, we used 13C-1H HSQC data to demonstrate that the Gal-3 CRD
      binds to the terminal, non-reducing end of these galactans, regardless of their
      size, but with binding affinity increasing as the galactan chain length
      increases. Overall, our findings increase understanding as to how galactans
      interact with Gal-3 at the non-reducing, terminal end of galactose-containing
      polysaccharides as found on the cell surface.

PMID- 30204869
TI  - miR-206 as a Biomarker for Response to Mesalamine Treatment in Ulcerative
      Colitis.
AB  - Background: MicroRNAs (miRNAs) are important post-translational regulators.
      Elevated levels of miR-206 in ulcerative colitis (UC) were associated with
      suppression of anti-inflammatory A3 adenosine receptor (A3AR) expression.
      However, the relationship of miR-206 to histologic remission in UC patients
      remains unknown. This study correlates expression levels of miR-206 with
      histologic remission in patients treated via long-term mesalamine treatment to
      identify a possible mode of action for this mainstay drug for UC. Methods:
      Expression of miR-206 and its target A3AR were analyzed in HT29 cell line before
      and after mesalamine treatment (2 mM) at different time points (0, 4, 12, and 24
      hours) by qRT-PCR and western blot analysis. Expression of miR-206 and
      pathological scores of colonoscopic biopsy specimens were studied in 10 UC
      patients treated with mesalamine treatment for 2 to 6 years. Results: miR-206
      transcripts decreased 2.23-fold (P = 0.0001) 4 hours after 2 mM mesalamine
      treatment in HT29 colon cells compared with untreated controls. However, the
      mRNA/protein levels of A3AR increased by 4-fold (P = 0.04) and 2-fold,
      respectively, in same cells. miR-206 relative expression decreased significantly
      in patients treated with 4.8 g of mesalamine (P = 0.002) but not with 2.4 g (P =
      0.35). Tissue assessment of sequential mesalamine-treated colonoscopic biopsies
      indicate a strong correlation between downregulation of miR-206 and histologic
      improvement (R = 0.9111). Conclusion: Mesalamine treatment has an effect on
      epithelial miRNAs. Downregulation of miR-206 by long-term mesalamine treatment
      may confer a protective effect in inducing and maintaining histologic remission.
      Thus, miR-206 expression levels can be utilized as a possible biomarker for
      therapeutic response to mesalamine treatment.

PMID- 30204866
TI  - Scaffold Proteins: From Coordinating Signaling Pathways to Metabolic Regulation.
AB  - Among their pleiotropic functions, scaffold proteins are required for the
      accurate coordination of signaling pathways. It has only been within the past 10
      years that their roles in glucose homeostasis and metabolism have emerged. It is
      well appreciated that changes in the expression or function of signaling
      effectors, such as receptors or kinases, can influence the development of chronic
      diseases such as diabetes and obesity. However, little is known regarding whether
      scaffolds have similar roles in the pathogenesis of metabolic diseases. In
      general, scaffolds are often underappreciated in the context of metabolism or
      metabolic diseases. In the present review, we discuss various scaffold proteins
      and their involvement in signaling pathways related to metabolism and metabolic
      diseases. The aims of the present review were to highlight the importance of
      scaffold proteins and to raise awareness of their physiological contributions. A
      thorough understanding of how scaffolds influence metabolism could aid in the
      discovery of novel therapeutic approaches to treat chronic conditions, such as
      diabetes, obesity, and cardiovascular disease, for which the incidence of all
      continue to increase at alarming rates.

PMID- 30204872
TI  - Small Bowel Ulcers on Capsule Endoscopy and Their Significance.

PMID- 30204873
TI  - Small Bowel Inflammation in Crohn's Disease and Other Conditions.

PMID- 30204874
TI  - What Is Stress? A Systems Perspective.
AB  - SYNOPSIS: The term "stress" is used to capture important phenomena at multiple
      levels of biological organization, but finding a general and rigorous definition
      of the concept has proven challenging. Current models in the behavioral
      literature emphasize the cognitive aspects of stress, which is said to occur when
      threats to the organism are perceived as uncontrollable and/or unpredictable.
      Here we adopt the perspective of systems biology and take a step toward a general
      definition of stress by unpacking the concept in light of control theory. Our
      goal is to clarify the concept so as to facilitate integrative research and
      formal analysis. We argue that stress occurs when a biological control system
      detects a failure to control a fitness-critical variable, which may be either
      internal or external to the organism. Biological control systems typically
      include both feedback (reactive, compensatory) and feedforward (predictive,
      anticipatory) components; their interplay accounts for the complex phenomenology
      of stress in living organisms. The simple and abstract definition we propose
      applies to animals, plants, and single cells, highlighting connections across
      levels of organization. In the final section of the paper we explore some
      extensions of our approach and suggest directions for future research.
      Specifically, we discuss the classic concepts of conditioning and hormesis and
      review relevant work on cellular stress responses; show how control theory
      suggests the existence of fundamental trade-offs in the design of stress
      responses; and point to potential insights into the effects of novel
      environmental conditions, including those resulting from anthropogenic change.

PMID- 30204871
TI  - Glucose Availability Predicts the Feeding Response to Ghrelin in Male Mice, an
      Effect Dependent on AMPK in AgRP Neurons.
AB  - Metabolic feedback from the periphery to the brain results from a dynamic
      physiologic fluctuation of nutrients and hormones, including glucose and fatty
      acids, ghrelin, leptin, and insulin. The specific interactions between humoral
      factors and how they influence feeding is largely unknown. We hypothesized that
      acute glucose availability may alter how the brain responds to ghrelin, a
      hormonal signal of energy availability. Acute glucose administration suppressed a
      range of ghrelin-induced behaviors as well as gene expression changes in
      hypothalamic neuropeptide Y (NPY) and agouti-related peptide (AgRP) neurons after
      ghrelin administration. Knockdown of the energy-sensing molecule AMP-activated
      protein kinase (AMPK) in AgRP neurons resulted in loss of the glucose effect, and
      mice responded as though pretreated with saline. Conversely, 2-deoxyglucose (2
      DG), which decreases glucose availability, potentiated ghrelin-induced feeding
      and increased hypothalamic NPY mRNA levels. AMPK knockdown did not alter the
      additive effect of 2-DG and ghrelin on feeding. Our findings support the idea
      that computation of energy status is dynamic, is informed by multiple signals,
      and responds to acute fluctuations in metabolic state. These observations are
      broadly relevant to the investigation of neuroendocrine control of feeding and
      highlight the underappreciated complexity of control within these systems.

PMID- 30204875
TI  - Orexin-A Levels in Relation to the Risk of Metabolic Syndrome in Patients with
      Schizophrenia Taking Antipsychotics.
AB  - Background: The role of orexin-A in regulating metabolic homeostasis has been
      recognized, but its association with antipsychotic-induced metabolic
      abnormalities remains unclear. We investigated the association between orexin-A
      levels and metabolic syndrome in patients with schizophrenia treated with
      clozapine or less obesogenic antipsychotics compared with nonpsychiatric
      controls. Methods: Plasma orexin-A levels and metabolic parameters were
      determined in 159 patients with schizophrenia: 109 taking clozapine; 50 taking
      aripiprazole, amisulpride, ziprasidone, or haloperidol; and 60 nonpsychiatric
      controls. Results: Orexin-A levels were significantly higher in the group taking
      less obesogenic antipsychotics, followed by the clozapine group and the controls
      (F=104.6, P<.01). Higher orexin-A levels were correlated with better metabolic
      profiles in the patient groups but not in the controls. Regression analyses
      revealed that the patients with higher orexin-A levels had significantly lower
      risk of metabolic syndrome (adjusted odds ratio [OR]=0.04, 95% CI: 0.01-0.38 for
      the 2nd tertile; OR=0.04, 95% CI: 0.01-0.36 for the 3rd tertile, compared with
      the first tertile), after adjustment for age, sex, smoking history, types of
      antipsychotics (clozapine vs less obesogenic antipsychotics), duration of
      antipsychotic treatment, and disease severity. Conclusions: Our results revealed
      that the orexin-A level was upregulated in patients with schizophrenia treated
      with antipsychotics, especially for the group taking less obesogenic
      antipsychotics. Furthermore, higher orexin-A levels were independently associated
      with better metabolic profiles. These observations suggest that an upregulation
      of orexin-A has a protective effect against the development of metabolic
      abnormalities in patients with schizophrenia receiving antipsychotic treatment.

PMID- 30204876
TI  - Effect of feeding cereals-alternative ingredients diets or corn-soybean meal
      diets on performance and carcass characteristics of growing-finishing gilts and
      boars.
AB  - Pig-breeding businesses have resulted in global breeding programs that select
      pigs to perform well on high-energy high-protein diets, which are traditionally
      based on corn and soybean meal. Nowadays, there is a shift toward diets based on
      cereals and co-products, therefore, high dietary inclusion of co-products can
      modify the expected performance of these pigs. The objective of this study was to
      evaluate the effect of feeding a cereals-alternative ingredients diet (CA-diet)
      compared to a corn-soybean meal diet (CS-diet) on the growth performance, feed
      efficiency, and carcass characteristics of genetically similar growing-finishing
      gilts and boars. In total, 160 pigs, 80 gilts and 80 boars, coming from 18
      litters were used. The pigs were blocked based on litter, to ensure no genetic
      differences between the 2 treatments. For the starter phase, pigs fed the CA-diet
      performed in terms of growth, and feed efficiency, as good as the pigs fed CS
      diet (P > 0.05). For the grower phase, pigs fed the CA-diet had the same ADFI (P
      > 0.05), but a lower daily energy intake (ADEI) (P < 0.001), and same growth
      performance (P > 0.05) than pig fed the CS-diet, therefore pigs fed the CA-diet
      were more efficient in terms of residual energy intake (REI) (P < 0.001). For the
      finisher phase, interaction between diet and sex had an effect on ADFI (P <
      0.001), ADEI (P < 0.001), ADG (P = 0.010), and lipid deposition (Ld) (P = 0.016).
      Pigs fed the CA-diet were less efficient than pigs fed the CS-diet, i.e., G:F (P
      < 0.001), RFI (P < 0.001), and REI (P = 0.007). In general, feeding a CA-diet to
      pigs showed to improve the ratio between Pd and Ld, especially for boars. Also,
      pigs fed the CA-diet showed thinner back fat thickness (P < 0.001), same loin
      depth thickness (P > 0.05), but lower dressing percentage (P < 0.001), than pigs
      fed the CS-diet.

PMID- 30204877
TI  - Abdominal aortic aneurysm with occlusion of three primary mesenteric vessels
      treated by surgery with perfusion of the left iliac artery.
AB  - A 64-year-old woman who underwent thoraco-abdominal aortic replacement for a
      Crawford type II aneurysm 11 years ago was referred to our hospital because of a
      residual juxtarenal abdominal aortic aneurysm. The coeliac, superior mesenteric
      and inferior mesenteric arteries were occluded. Collateral vessels from the left
      internal iliac artery to these 3 mesenteric arteries had developed. We performed
      open aneurysm repair using an extracorporeal circuit to maintain collateral flow
      to these mesenteric arteries.

PMID- 30204878
TI  - Clostridioides (formerly Clostridium) difficile infection during hospitalization
      increases the likelihood of non-home patient discharge.
AB  - Background: Clostridioides (formerly Clostridium) difficile infection (CDI) is
      associated with significant morbidity and mortality, including frequent
      hospitalizations. However, the impact of CDI post-hospital discharge is poorly
      understood. The purpose of this study was to assess patient discharge disposition
      and understand CDI-related risk factors for non-home discharge. Methods: Using a
      nationally representative database of Veterans Health Administration (VHA)
      patients (2003-2014) and a validation database from hospitalized non-VHA patients
      in Houston, Texas, admission and discharge disposition was obtained for patients
      with CDI and matched controls. Incidence of and clinical/microbiologic risk
      factors for non-home discharge were assessed using these databases. Results: A
      total of 15,173 VHA patients with CDI and 48,599 non-CDI control patients
      originally admitted from the community were included. Significantly more patients
      with CDI were discharged to a non-home location (18%) compared to controls (8%;
      p<0.0001), most commonly hospice/death (12%) or nursing home/long-term care
      facility (6%). Results were confirmed using a propensity matched analysis and a
      validation cohort of 1,941 hospitalized patients with CDI in Houston, TX. Age,
      comorbidities, severe CDI, and ribotypes F027, F001, and F053-163 were associated
      with a non-home discharge (p<0.05 for all). Conclusions: Hospitalized patients
      with CDI frequently required a higher level of medical care residence at
      discharge compared to non-CDI patients. Risk factors for discharge to a higher
      level of care included CDI disease severity and variables associated with
      recurrent CDI.

PMID- 30204879
TI  - Loss of Biodiversity Dimensions through Shifting Climates and Ancient Mass
      Extinctions.
AB  - Many aspects of climate affect the deployment of biodiversity in time and space,
      and so changes in climate might be expected to drive regional and global
      extinction of both taxa and their ecological functions. Here we examine the
      association of past climate changes with extinction in marine bivalves, which are
      increasingly used as a model system for macroecological and macroevolutionary
      analysis. Focusing on the Cenozoic Era (66 Myr ago to the present), we analyze
      extinction patterns in shallow-water marine bivalve genera relative to
      temperature dynamics as estimated from isotopic data in microfossils. When the
      entire Cenozoic timeseries is considered, extinction intensity is not
      significantly associated with the mean temperature or the detrended variance in
      temperature within a given time interval (stratigraphic stage). However,
      extinction increases significantly with both the rate of temperature change
      within the stage of extinction and the absolute change in mean temperature from
      the preceding stage to the stage of extinction. Thus, several extinction events,
      particularly the extinction pulse near the Pliocene-Pleistocene boundary, do
      appear to have climatic drivers. Further, the latitudinal diversity gradient
      today and the Cenozoic history of polar faunas suggest that long-term, regional
      extinctions associated with cooling removed not just taxa but a variety of
      ecological functions from high-latitude seas. These dynamics of biodiversity loss
      contrast with the two mass extinctions bracketing the Mesozoic Era, which had
      negligible effects on the diversity of ecological functions despite removing
      nearly as many taxa as the latitudinal gradient does today. Thus, the fossil
      record raises a key issue: whether the biotic consequences of present-day
      stresses will more closely resemble the long-term effects of past climate changes
      or those that cascaded from the mass extinctions.

PMID- 30204880
TI  - A newly isolated Pex7-binding, atypical PTS2 protein P7BP2 is a novel dynein-type
      AAA+ protein.
AB  - A newly isolated binding protein of peroxisomal targeting signal type 2 (PTS2)
      receptor Pex7, termed P7BP2, is transported into peroxisomes by binding to the
      longer isoform of Pex5p, Pex5pL, via Pex7p. The binding to Pex7p and peroxisomal
      localization of P7BP2 depends on the cleavable PTS2 in the N-terminal region,
      suggesting that P7BP2 is a new PTS2 protein. By search on human database, three
      AAA+ domains are found in the N-terminal half of P7BP2. Protein sequence
      alignment and motif search reveal that in the C-terminal region P7BP2 contains
      additional structural domains featuring weak but sufficient homology to AAA+
      domain. P7BP2 behaves as a monomer in gel-filtration chromatography and the
      single molecule observed under atomic force microscope shapes a disc-like ring.
      Collectively, these results suggest that P7BP2 is a novel dynein-type AAA+ family
      protein, of which domains are arranged into a pseudo-hexameric ring structure.

PMID- 30204882
TI  - The psychological impact of early pregnancy loss.
AB  - BACKGROUND: Early pregnancy loss (EPL) is a common event, with scope for long
      term personal and societal impact. There are three decades worth of published
      evidence of profound psychological sequelae in a significant proportion of women.
      However, the wide variety of outcomes, screening instruments, assessment timings
      and geographical locations makes it challenging to form a coherent picture of the
      morbidity within the whole group and its subgroups. OBJECTIVE AND RATIONALE: This
      review aims to investigate three questions. (1) What is the evidence for
      depression, anxiety and post-traumatic stress disorder (PTSD) following a
      miscarriage or an ectopic pregnancy in women and/or their partners? (2) What is
      the intensity and duration of these conditions, and how do they compare to those
      without losses? (3) Which patients have been found to be at highest risk of
      psychopathology? Answers to these questions are salient not only in day-to-day
      clinical interactions with those experiencing EPL, whose psychological needs may
      not be prioritized, but should also form the basis for tailoring healthcare
      policy in terms of screening for and treating the associated psychological
      morbidity. SEARCH METHODS: The following databases were searched, from the start
      of each database up to July 2017: MEDLINE (Ovid interface, 1948 onwards), Embase
      classic + Embase (Ovid interface, 1947 onwards), and PsychINFO (Ovid interface,
      1806 onwards). Search strategies were developed using medical subject headings
      (MeSH). The concepts of psychological morbidity (anxiety, depression or PTSD) and
      pregnancy loss (miscarriage or ectopic pregnancy) were first expanded with the
      Boolean operator 'or', then linked together using 'and'. Included studies were of
      prospective cohort design, including women or men following EPL (with the
      majority to have experienced losses before 24 weeks gestation), and reporting
      standardized psychometric measures for anxiety, depression and post-traumatic
      stress disorder. The timing of follow-up had to be specified and standardized
      across participants. Manuscript quality and risk of bias was assessed using the
      Newcastle-Ottawa Scale. OUTCOMES: We found evidence of significant depression and
      anxiety in the first month following EPL in women. Partners were also shown to
      display depression and anxiety, albeit to a generally lower level. There is also
      evidence of post-traumatic stress symptoms relating to the EPL in three studies.
      WIDER IMPLICATIONS: In view of their high frequency, EPLs can significantly
      contribute to the overall burden of psychopathology within a population.
      Recognition of this impact is important, so that severely affected individuals
      may be screened and treated appropriately. Further research to establish risk
      factors to promptly identify and treat these patients, and to optimize their
      management, is crucial.

PMID- 30204881
TI  - Genetic parameters for fertility and production traits in Red Angus cattle.
AB  - Heifer pregnancy (HPG) and Stayability (STAY) are female reproductive traits that
      have EPD reported by the Red Angus Association of America. Challenges arise when
      making genetic predictions for these traits. Specifically, HPG and STAY
      phenotypes can only be collected on females retained in the breeding herd and
      have low heritability estimates. Additionally, STAY is measured late in an
      animal's life. The objective of this research was to investigate the genetic
      relationships between HPG or STAY and 13 other traits, which included
      measurements of growth, carcass, ultrasound, and scrotal circumference. For STAY
      relationships between mature weight (MW), body condition score (BCS), teat score
      (TS), and udder suspension score (US) were also evaluated. Data from 142,146 and
      164,235 animals were used in the analyses for HPG and STAY, respectively. Genetic
      relationships were investigated using a series of 2 trait animal models and a
      REML procedure. In all analyses, the appropriate contemporary groups were
      included as a fixed effect, and direct genetic as a random effect. Additional
      fixed effects included as follows: sex for weight, carcass and ultrasound traits,
      age of dam for weight traits, and age of measurement for ultrasound, carcass,
      BCS, udder traits, and MW. Maternal genetic effects for preweaning gain (Pre-WG),
      weaning weight (WW), and yearling weight (YW) were also modeled. Permanent
      environmental effects of the dam were modeled for the traits Pre-WG and WW.
      Permanent environment of the individual for the traits MW, BCS, TS, and US was
      also included. Heritability estimates were 0.12 +/- 0.01 and 0.10 +/- 0.01 for
      HPG and STAY, respectively. Heritability estimates for direct genetic effects of
      production traits were moderate to high in magnitude, maternal heritability
      estimates were low, and permanent environmental effects accounted for 0.00 to
      0.18 of the total variation. The strongest genetic correlations were those among
      Pre-WGD (0.24 +/- 0.08), WWD (0.18 +/- 0.08), YWD (0.20 +/- 0.07), ultrasound rib
      eye area direct (0.16 +/- 0.08), and ultrasound backfat direct (0.14 +/- 0.08)
      and HPG. The highest genetic correlations were between STAY and WWM (0.54 +/-
      0.05), YWM (0.36 +/- 0.07), backfat (0.53 +/- 0.20), marbling score (0.40 +/-
      0.20), UREA (0.19 +/- 0.07), ultrasound backfat (0.37 +/- 0.07), TS (0.30 +/-
      0.11), and US (0.23 +/- 0.11). Relationships between HPG or STAY and other traits
      were minimal. These results suggest that genetic relationships exist between HPG
      or STAY and other more densely recorded traits.

PMID- 30204883
TI  - Views and experiences of ethnic minority diabetes patients on dietetic care in
      the Netherlands - a qualitative study.
AB  - Background: Diabetes type 2 is more prevalent in people from ethnic minorities in
      the Netherlands, and outcomes of care are worse compared with other Dutch people.
      Dieticians experience difficulties in managing these groups in self-management
      and adherence to dietary advice. The aim of this study was to explore the views
      regarding a healthy diet and dietetic care among ethnic minority type 2 diabetes
      patients. Methods: Semi-structured interviews were held with 12 migrants with
      diabetes from Turkey, Morocco, Iraq and Curacao, who visited a dietician.
      Inclusion went on until saturation was reached. The interview guide was based on
      the Attitudes, Social influence and self-Efficacy (ASE) model and Kleinman's
      explanatory model of illness. Interviews were held in the language preferred by
      the respondent. Transcripts were coded and thematically analyzed. Results:
      Several respondents expected a more rigorous, directive and technical approach of
      the dietician. All respondents acknowledged the importance of a healthy diet.
      What they considered healthy was determined by culturally influenced ideas about
      health benefits of specific foods. Important hindrances for dietary change were
      lack of self-efficacy and social support. Social influences were experienced both
      as supportive and a hindrance. Conclusions: Migrant diabetic patients' opinions
      about healthy food are determined by culturally influenced ideas rather than by
      dietary guidelines. Dutch dietary care is not tailored to the needs of these
      patients and should take into account migrants' expectations, cultural
      differences in dietary habits and specifically address the role of family.

PMID- 30204885
TI  - Daily Maternal Lipid-Based Nutrient Supplementation with 20 mg Iron, Compared
      with Iron and Folic Acid with 60 mg Iron, Resulted in Lower Iron Status in Late
      Pregnancy but Not at 6 Months Postpartum in Either the Mothers or Their Infants
      in Bangladesh.
AB  - Background: Maternal anemia and iron deficiency are prevalent in low- and middle
      income countries. Objective: We aimed to determine the effects of lipid-based
      nutrient supplements for pregnant and lactating women (LNS-PL) on hemoglobin
      (Hb), anemia, and iron status (nonprimary outcomes) at 36 weeks of gestation
      (women) and 6 mo postpartum (women and infants). Methods: The Rang-Din Nutrition
      Study, a cluster-randomized effectiveness trial, enrolled 4011 Bangladeshi
      pregnant women at <=20 weeks of gestation to receive either daily LNS-PL (20 mg
      Fe) during pregnancy and the first 6 mo postpartum, or iron and folic acid (IFA,
      60 mg Fe + 400 ug folic acid) daily during pregnancy and every other day during
      the first 3 mo postpartum. Biochemical measurements from a subsample of women (n
      = 1128) and their infants (n = 1117) included Hb (g/L), serum ferritin (ug/L),
      and soluble transferrin receptor (sTfR; mg/L). Anemia was defined as maternal Hb
      <110 g/L at 36 weeks of gestation, <120 g/L at 6 mo postpartum, or infant Hb <105
      g/L; iron deficiency (ID) was defined as ferritin <12 ug/L or elevated sTfR (>8.3
      mg/L for women and >11 mg/L for infants). Results: Compared with the IFA group,
      women in the LNS-PL group had lower ferritin (-6.2 ug/L; P < 0.001) and higher
      sTfR concentrations (+0.5 mg/L; P < 0.001), and higher risk of ID (OR = 1.93; P <
      0.05) at 36 weeks of gestation but not at 6 mo postpartum, whereas no consistent
      differences were observed for Hb or anemia. Among infants at 6 mo, there were no
      group differences except for a lower risk of elevated sTfR (OR = 0.61; P < 0.05)
      in the LNS-PL group than in the IFA group. Conclusions: Provision of LNS-PL
      including a lower dose of iron than what is recommended during pregnancy resulted
      in differences in maternal iron status in late pregnancy that disappeared by 6 mo
      postpartum, and caused no undesirable effects regarding anemia or iron status of
      infants. This trial was registered at clinicaltrials.gov as NCT01715038.

PMID- 30204886
TI  - Cooking Conditions Affect the True Ileal Digestible Amino Acid Content and
      Digestible Indispensable Amino Acid Score (DIAAS) of Bovine Meat as Determined in
      Pigs.
AB  - Background: Cooking processes affect the physical, chemical, and structural
      properties of meat proteins. Cooking may also affect the protein quality of meat,
      as indicated by the true ileal digestibility of individual amino acids, the
      content of each truly digestible amino acid, and the digestible indispensable
      amino acid score (DIAAS). Objective: The study aimed to determine the effect of
      the cooking process (raw, not cooked; boiled; grilled; pan-fried; roasted) of
      beef on true (standardized) ileal amino acid digestibility, true ileal digestible
      amino acid content, and DIAAS. Methods: Beef topside steak was subjected to one
      of the following conditions: raw, boiled, grilled, pan-fried, or roasted,
      followed by mincing. The growing pig was used as an animal model for the adult
      human. Diets containing the raw or cooked meats (10% crude protein content) were
      fed to growing pigs (n = 6 per diet; mean +/- SEM bodyweight, 23.6 +/- 0.48 kg)
      and samples of terminal ileal digesta were collected under anesthesia. True ileal
      amino acid digestibility of the beef was determined and DIAAS values were
      calculated. Results: There were only minor differences in true ileal amino acid
      digestibility across cooking conditions with all amino acids having true ileal
      amino acid digestibility in the range of 90-100%. In general, boiled meat had the
      highest true ileal digestible amino acid content (total of 724 g/kg dry matter),
      and roasted meat the lowest (total of 641 g/kg dry matter; P < 0.001). The DIAAS
      was greater (P < 0.001) for the raw, boiled, and pan-fried meat treatments (97
      99%) than for roasted meat (91%) or grilled meat (80%). The high DIAAS (range 80
      99%) across cooking conditions confirms that bovine meat is a high-quality
      protein source. Conclusion: Cooking conditions affect the true ileal digestible
      amino acid content and DIAAS of beef, as determined with the use of the pig
      model.

PMID- 30204884
TI  - Glutathione content and expression of proteins involved with glutathione
      metabolism differs in longissimus dorsi, subcutaneous adipose, and liver tissues
      of finished vs. growing beef steers.
AB  - Increased tissue redox state may result in sub-optimal growth. Our goal was to
      determine if glutathione (GSH) content and expression of proteins involved with
      GSH metabolism change in longissimus dorsi (LD), subcutaneous adipose (SA), and
      liver tissues of growing vs. finishing steer phenotypes. Tissues were taken from
      16 Angus steers (BW = 209 +/- 29.4 kg) randomly assigned (n = 8) to develop
      through Growing (final BW = 301 +/- 7.06 kg) vs. Finished (final BW = 576 +/-
      36.9 kg) growth phases, and at slaughter had achieved different rib-eye area
      (REA) (53.2, 76.8 cm2), marbling scores (296, 668), and 12th rib adipose
      thickness (0.54, 1.73 cm), respectively (Amino Acids, doi:10.1007/s00726-018-2540
      8). GSH content (mg/g wet tissue) was determined by a commercial assay and the
      relative content of target protein and mRNA in tissue homogenates was determined
      by Western blot and reverse-transcribed PCR analyses, respectively. The effect of
      growth phase (Finished vs. Growing) was assessed by ANOVA using the GLM procedure
      of SAS. The LD of Finished steers had more (P < 0.04) GSH (42%) and GSH
      synthesizing (GCLC, 61%; GCLM, 21%) and metabolizing (GPX1, 42%; GPX3, 73%; GGT1,
      56%) enzymes, and less (P < 0.02) GPX2 (46%), EAAC1 (30%) and glutamine
      synthetase (GS) (28%), whereas GTRAP3-18 and ARL6IP1 did not differ (P > 0.57).
      Principal component analysis found that GSH content of LD was associated with REA
      and marbling score. The SA of Finished steers had less (P < 0.04) GSH (38%), GSH
      metabolizing (GPX4, 52%; GGT1, 71%) enzyme mRNA, and GTRAP3-18 (123%) and ARL6IP1
      (43%), whereas the mRNA content of GSH-synthesizing enzymes and content of EAAC1
      and GS did not differ (P > 0.32). The liver of Finished steers had less (P <
      0.02) mRNA content of GSH synthesizing (GCLC, 39%; GSS 29%) and metabolizing
      (GPX1, 30%) enzymes, and more (P < 0.01) GSTM1 metabolizing enzyme (114%). The
      change in GSH content as steers fattened indicate an increased antioxidant
      capacity in the LD of Finished steers, and a decreased antioxidant capacity in
      SA, consistent with changes in enzyme and transporter expression. Changes in
      liver enzyme and transporter expression were consistent with no change in GSH
      content. The relationship of EAAC1 regulatory proteins (GTRAP3-18, ARL6IP1) to
      GSH, EAAC1, and GS content differs and changes as Growing steers develop into
      Finished phenotypes. These findings provide mechanistic insight into how
      antioxidant capacity occurs in tissues of economic and metabolic importance as
      cattle fatten.

PMID- 30204887
TI  - The WUSCHEL-related homeobox1 gene of cucumber regulates reproductive organ
      development.
AB  - The WUSCHEL-related homeobox1 (WOX1) transcription factor plays an important role
      in lateral growth of plant organs; however, the underlying mechanisms in the
      regulation of reproductive development are largely unknown. Cucumber (Cucumis
      sativus) has separate male and female flowers, facilitating the study of the role
      of WOX1 in stamen and carpel development. Here, we identified a mango fruit (mf)
      mutant in cucumber, which displayed multiple defects in flower growth as well as
      male and female sterility. Map-based cloning showed that Mf encodes a WOX1-type
      transcriptional regulator (CsWOX1), and that the mf mutant encodes a truncated
      protein lacking the conserved WUS box. Further analysis showed that elevated
      expression of CsWOX1 was responsible for the mutant phenotype in cucumber and
      Arabidopsis. Comparative transcriptome profiling revealed certain key players and
      CsWOX1-associated networks that regulate reproductive development. CsWOX1
      directly interacts with cucumber SPOROCYTELESS (CsSPL), and many genes in the
      CsSPL-mediated pathway were down-regulated in plants with the mutant allele at
      the Mf locus. In addition, auxin distribution was affected in both male and
      female flowers of the mutant. Taking together, these data suggest that CsWOX1 may
      regulate early reproductive organ development and be involved in sporogenesis via
      the CsSPL-mediated pathway and/or modulate auxin signaling in cucumber.

PMID- 30204888
TI  - Back pain, mental health and substance use are associated in adolescents.
AB  - Background: During adolescence, prevalence of pain and health risk factors such
      as smoking, alcohol use and poor mental health all rise sharply. The aim of this
      study was to describe the relationship between back pain and health risk factors
      in adolescents. Methods: Cross-sectional data from the Healthy Schools Healthy
      Futures study, and the Australian Child Wellbeing Project was used, mean age: 14
      15 years. Children were stratified according to back pain frequency. Within each
      strata, the proportion of children that reported drinking alcohol or smoking or
      that experienced feelings of anxiety or depression was reported. Test-for-trend
      analyses assessed whether increasing frequency of pain was associated with health
      risk factors. Results: Data was collected from ~2500 and 3900 children. Larger
      proportions of children smoked or drank alcohol within each strata of increasing
      pain frequency. The trend with anxiety and depression was less clear, although
      there was a marked difference between the children that reported no pain, and
      pain more frequently. Conclusion: Two large, independent samples show adolescents
      that experience back pain more frequently are also more likely to smoke, drink
      alcohol and report feelings of anxiety and depression. Pain appears to be part of
      the picture of general health risk in adolescents.

PMID- 30204889
TI  - How Respiratory Syncytial Virus Genotypes Influence the Clinical Course in
      Infants Hospitalized for Bronchiolitis.
AB  - Background: We aimed to study respiratory syncytial virus (RSV) genotype
      distribution, clinical presentation, and disease severity in infants with
      bronchiolitis from RSV subtypes and new RSV genotypes. Methods: We prospectively
      enrolled previously healthy term infants less than 1 year old hospitalized for
      bronchiolitis in an Italian university hospital over 12 epidemic seasons. In 312
      nasopharyngeal washings positive for RSV, we sequenced the viral genotype and
      analyzed this according to patient data. Strain-specific RSV loads were
      quantified for 273 specimens. Results: From 2005-2006 to 2011-2012, the RSV-A
      genotype NA1 predominated, and was replaced in 2012 by the novel ON1. All infants
      infected with RSV subtype B were genotype BA. Stratifying data according to
      genotypes NA1, ON1, and BA showed that NA1-infected infants were the youngest and
      had the most severe clinical course. Conversely, BA-infected infants had less
      severe symptoms and more frequently had eosinophilia and a family history of
      asthma. Infants with the ON1 genotype had a milder clinical course than those
      with NA1 and more risk factors for asthma, despite having the highest viral
      loads. Conclusion: The disease course in infants hospitalized for acute RSV
      bronchiolitis may depend on the RSV genotype.

PMID- 30204890
TI  - Scandinavian Multicenter Acute Subdural Hematoma (SMASH) Study: Study Protocol
      for a Multinational Population-Based Consecutive Cohort.

PMID- 30204891
TI  - The Hidden Nature of Protein Translational Control by Diphthamide - the secrets
      under the leather.
AB  - The protein translation elongation factor eEF2 undergoes a unique
      posttranslational modification called diphthamidation. eEF2 is an essential
      factor in protein translation, and the diphthamide modification has been a famous
      target of the diphtheria toxin for a long time. On the other hand, the
      physiological function of this rare modification in vivo remains unknown. Recent
      studies have suggested that diphthamide has specific functions for the cellular
      stress response and active proliferation. In this review, we summarize the
      history and findings of diphthamide obtained to date and discuss the possibility
      of a specific function for diphthamide in regulating protein translation.

PMID- 30204892
TI  - Rad54/Rad54B deficiency is associated to increased chromosome breakage in mouse
      spermatocytes.
AB  - Rad54 protein is a key player of the homologous recombination pathway, required
      for deposition and stabilisation of Rad51 foci at double strand breaks. Its role
      at the meiotic prophase, when double strand breaks are physiologically introduced
      to allow recombination, is well described. However, the hypothesis that Rad54
      deficiency affect chromosome integrity of germ cells in unirradiated and
      irradiated animals has not been tested yet. In this study, the occurrence of
      spontaneous and X-ray-induced chromosome aberrations was assessed by analysis of
      spermatocyte MI spreads or by application of micronucleus assay in early
      spermatids isolated from wild type and Rad54/Rad54B knockout (KO) mice. In
      Rad54/Rad54B KO mice, the spontaneous chromosome aberration frequency detected at
      MI was >10-fold higher than in wild type animals. In addition, after exposure to
      1 Gy X-rays at the radiosensitive stage of diplotene, an enhanced response to
      radiation was observed in Rad54-deficient animals, corresponding to a 2-3
      sensitivity factor in comparison to wild type mice. Also the spontaneous
      frequency of micronucleated round spermatids was on the average 10-fold higher in
      KO than in wild type mice, indicating that Rad54/Rad54B KO spermatocytes carrying
      chromosome aberrations are able to pass through the meiotic divisions and to
      continue the spermatogenesis process. Our results provide the first evidence of
      the role of Rad54/Rad54B in the maintenance of a stable karyotype during male
      meiosis, and suggest that Rad54/Rad54B deficiency may impact on the DNA integrity
      of developing mouse gametes.

PMID- 30204893
TI  - Correlates of Benzodiazepine Use and Adverse Outcomes Among Patients with Chronic
      Pain Prescribed Long-term Opioid Therapy.
AB  - Objective: To examine the correlates and odds of receiving overlapping
      benzodiazepine and opioid prescriptions and whether co-prescription was
      associated with greater odds of falling or visiting the emergency department.
      Design: Cross-sectional study. Setting: A large private integrated health system
      and a Veterans Health Administration integrated health system. Subjects: Five
      hundred seventeen adults with musculoskeletal pain and current prescriptions for
      long-term opioid therapy. Methods: A multivariate logistic regression model
      examined correlates of having overlapping benzodiazepine and opioid prescriptions
      in the year before enrollment in the cross-sectional study. Negative binomial
      models analyzed the number of falls in the past three months and past-year
      emergency department visits. In addition to propensity score adjustment, models
      controlled for demographic characteristics, psychiatric diagnoses, medications,
      overall comorbidity score, and opioid morphine equivalent dose. Results: Twenty
      five percent (N = 127) of participants had co-occurring benzodiazepine and opioid
      prescriptions in the prior year. Odds of receiving a benzodiazepine prescription
      were significantly higher among patients with the following psychiatric
      diagnoses: anxiety disorder (adjusted odds ratio [AOR] = 4.71, 95% confidence
      interval [CI] = 2.67-8.32, P < 0.001), post-traumatic stress disorder (AOR =
      2.24, 95% CI = 1.14-4.38, P = 0.019), and bipolar disorder (AOR = 3.82, 95% CI =
      1.49-9.81, P = 0.005). Past-year overlapping benzodiazepine and opioid
      prescriptions were associated with adverse outcomes, including a greater number
      of falls (risk ratio [RR] = 3.27, 95% CI = 1.77-6.02, P = 0.001) and emergency
      department visits (RR = 1.66, 95% CI = 1.08-2.53, P = 0.0194). Conclusions: Among
      patients with chronic pain prescribed long-term opioid therapy, one-quarter of
      patients had co-occurring prescriptions for benzodiazepines, and dual use was
      associated with increased odds of falls and emergency department visits.

PMID- 30204894
TI  - Transcriptome-Derived Microsatellites Demonstrate Strong Genetic Differentiation
      in Pacific White Sharks.
AB  - Recent advances in genome-scale sequencing technology have allowed the
      development of high resolution genetic markers for the study of nonmodel taxa. In
      particular, transcriptome sequencing has proven to be highly useful in generating
      genomic markers for use in population genetic studies, allowing for insight into
      species connectivity, as well as local adaptive processes as many transcriptome
      derived markers are found within or associated with functional genes. Herein, we
      developed a set of 30 microsatellite markers from a heart transcriptome for the
      white shark (Carcharodon carcharias), a widely distributed and globally
      vulnerable marine predator. Using these markers as well as 10 published anonymous
      genomic microsatellite loci, we provide 1) the first nuclear genetic assessment
      of the cross-Pacific connectivity of white sharks, and 2) a comparison of the
      levels of inferred differentiation across microsatellite marker sets (i.e.,
      transcriptome vs. anonymous) to assess their respective utility to elucidate the
      population genetic dynamics of white sharks. Significant (FST = 0.083, P = 0.05;
      G"ST = 0.200; P = 0.001) genetic differentiation was found between Southwestern
      Pacific (n = 19) and Northeastern Pacific (n = 20) white sharks, indicating
      restricted, cross Pacific gene flow in this species. Transcriptome-derived
      microsatellite marker sets identified much higher (up to 2*) levels of genetic
      differentiation than anonymous genomic markers, underscoring potential utility of
      transcriptome markers in identifying subtle population genetic differences within
      highly vagile, globally distributed marine species.Subject areas: Population
      structure and phylogeography; Conservation genetics and biodiversity.

PMID- 30204895
TI  - Psychometric Evaluation of a Pain Intensity Measure for Persons with Dementia.
AB  - Objective: The goal of this study was to conduct initial psychometric analyses of
      a seven-item pain intensity measure for persons with dementia (PIMD) that was
      developed using items from existing pain observational measures. Design and
      Methods: We evaluated validity by examining associations with an expert
      clinician's pain intensity rating (ECPIR) and an established pain observation
      tool (Mobilization Observation Behaviour Intensity Dementia [MOBID]). We also
      examined correlations between the PIMD and known correlates of pain: depression,
      sleep disturbances, agitation, painful diagnoses, and caregiver pain reports. We
      examined the differences between PIMD scores for "at rest" and "during movement"
      observations. We assessed reliability by calculating Cronbach's alpha and
      estimating inter-rater reliability using intraclass correlations (ICCs). Finally,
      we examined whether six additional "recent changes in behavior" items improved
      the PIMD's ability to predict expert clinicians' pain ratings. Setting: Sixteen
      nursing homes located in Alabama, Georgia, Pennsylvania, and New Jersey.
      Participants: One hundred ninety residents with moderate to severe cognitive
      impairment, mean age of 84 years, 49.5% female, and 70% white. Results: PIMD
      during movement scores were highly correlated with the ECPIR and overall MOBID
      scores. As expected, there were large differences between at rest and during
      movement PIMD scores. Associations of PIMD with known correlates of pain were
      generally low and statistically nonsignificant. Internal consistency was
      supported with a Cronbach alpha of 0.72 and an inter-rater ICC of 0.82 for during
      movement PIMD scores. Conclusions: Initial evaluation of the PIMD supports its
      validity and reliability. Additional testing is needed to evaluate the tool's
      sensitivity to changes in pain intensity.

PMID- 30204896
TI  - Autoantibody status is not associated with early treatment response to first-line
      methotrexate in patients with early rheumatoid arthritis.
AB  - Objectives: In RA, the relationship between autoantibody status and treatment
      response to MTX remains unclear. We investigated the association between
      autoantibody status and early remission in newly diagnosed RA patients treated
      with MTX using real-world data. Methods: RA-patients initially treated with MTX
      were selected from an international observational database (METEOR). Patients
      were stratified into autoantibody-positive (RF- and/or ACPA-positive) or
      autoantibody negative (RF- and ACPA-negative). The effect of autoantibody status
      on the chance of achieving remission within 3 to 6 months was analysed using Cox
      proportional hazards regression. Results: Data from 1826 RA patients were
      available for analysis. DAS remission was achieved in 17% (318/1826). This was
      similar in autoantibody-positive [17% (282/1629)] and -negative patients [18%
      (36/197)]. Hence, autoantibody positivity was not associated with remission
      [hazard ratio (HR) 0.89, 95% CI 0.57, 1.38]. Similar findings were found when
      stratified for MTX monotherapy (HR 0.75, 95% CI 0.41, 1.37) or combination
      treatment (HR 0.76, 95% CI 0.37, 1.54). Good physical function (HAQ < 0.5) was
      achieved in 33% (530/1590) of all patients. Autoantibody-positivity was also not
      associated with HAQ < 0.5 (HR 1.05, 95% CI 0.71, 1.57). Conclusion: Autoantibody
      status is not associated with early remission in newly diagnosed RA-patients
      receiving MTX. This indicates that MTX is effective as an initial treatment
      strategy regardless of autoantibody status.

PMID- 30204897
TI  - AnimalTFDB 3.0: a comprehensive resource for annotation and prediction of animal
      transcription factors.
AB  - The Animal Transcription Factor DataBase (AnimalTFDB) is a resource aimed to
      provide the most comprehensive and accurate information for animal transcription
      factors (TFs) and cofactors. The AnimalTFDB has been maintained and updated for
      seven years and we will continue to improve it. Recently, we updated the
      AnimalTFDB to version 3.0 (http://bioinfo.life.hust.edu.cn/AnimalTFDB/) with more
      data and functions to improve it. AnimalTFDB contains 125,135 TF genes and 80,060
      transcription cofactor genes from 97 animal genomes. Besides the expansion in
      data quantity, some new features and functions have been added. These new
      features are: (i) more accurate TF family assignment rules; (ii) classification
      of transcription cofactors; (iii) TF binding sites information; (iv) the GWAS
      phenotype related information of human TFs; (v) TF expressions in 22 animal
      species; (vi) a TF binding site prediction tool to identify potential binding TFs
      for nucleotide sequences; (vii) a separate human TF database web interface
      (HumanTFDB) was designed for better utilizing the human TFs. The new version of
      AnimalTFDB provides a comprehensive annotation and classification of TFs and
      cofactors, and will be a useful resource for studies of TF and transcription
      regulation.

PMID- 30204898
TI  - Defatted Microalgae-Mediated Enrichment of n-3 Polyunsaturated Fatty Acids in
      Chicken Muscle Is Not Affected by Dietary Selenium, Vitamin E, or Corn Oil.
AB  - Background: We previously showed enrichments of docosahexaenoic acid (DHA) and
      eicosapentaenoic acid (EPA) in broiler chicks fed defatted microalgae.
      Objectives: The aims of this study were to determine 1) if the enrichments
      affected meat texture and were enhanced by manipulating dietary corn oil,
      selenium, and vitamin E concentrations and 2) how the enrichments corroborated
      with hepatic gene expression involved in biosynthesis and oxidation of EPA and
      DHA. Methods: Day-old hatching Cornish Giant cockerels (n = 216) were divided
      into 6 groups (6 cages/group and 6 chicks/cage). Chicks were fed 1 of the 6
      diets: a control diet containing 4% corn oil, 25 IU vitamin E/kg, and 0.2 mg
      Se/kg (4CO), 4CO + 10% microalgae (defatted Nannochloropsis oceanica; 4CO+ MA),
      4CO+ MA - 2% corn oil (2CO+MA), 2CO+MA + 75 IU vitamin E/kg (2CO+MA+E), 2CO+MA +
      0.3 mg Se/kg (2CO+MA+Se), and 2CO+MA+E + 0.3 mg Se/kg (2CO+MA+E+Se). After 6 wk,
      fatty acid profiles, DHA and EPA biosynthesis and oxidation, gene expression,
      lipid peroxidation, antioxidant status, and meat texture were measured in liver,
      muscles, or both. Results: Compared with the control diet, defatted microalgae
      (4CO+MA) enriched (P < 0.05) DHA and EPA by <=116 and 24 mg/100 g tissue in the
      liver and muscles, respectively, and downregulated (41-76%, P < 0.01) hepatic
      mRNA abundance of 4 cytochrome P450 (CYP) enzymes (CYP2C23b, CYP2D6, CYP3A5,
      CYP4V2). Supplemental microalgae decreased (50-82%, P < 0.05) lipid peroxidation
      and improved (16-28%, P < 0.05) antioxidant status in the liver, muscles, or
      both. However, the microalgae-mediated enrichments in the muscles were not
      elevated by altering dietary corn oil, vitamin E, or selenium and did not affect
      meat texture. Conclusion: The microalgae-mediated enrichments of DHA and EPA in
      the chicken muscles were associated with decreased hepatic gene expression of
      their oxidation, but were not further enhanced by altering dietary corn oil,
      vitamin E, or selenium.

PMID- 30204899
TI  - Wheat WD40-repeat protein TaHOS15 functions in a histone deacetylase complex to
      fine-tune defense response to Blumeriagraminis f.sp. tritici.
AB  - Powdery mildew caused by Blumeriagraminis f.sp. tritici (Bgt) seriously threatens
      the production of common wheat (Triticumaestivum L.). In eukaryotes, WD40-repeat
      (WDR) proteins usually participate in assembling protein complexes involved in a
      wide range of cellular processes. However, the potential function of WDR proteins
      in regulating crop resistance against biotrophic fungal pathogens, such as Bgt,
      remains unclear. In this study, we isolated TaHOS15, encoding a WDR protein, from
      wheat cultivar Jing411 and demonstrated that knockdown of TaHOS15 expression
      using virus- or transient-induced gene silencing attenuated wheat susceptibility
      to Bgt. The biochemical and molecular-biological assays revealed that TaHOS15
      interacts with TaHDA6, a wheat homolog of Arabidopsis histone deacetylase AtHDA6,
      to constitute a transcriptional repressor complex. Furthermore, we defined the
      role of TaHOS15, which might act as an adaptor protein recruiting TaHDA6 to the
      chromatin of wheat defense-related genes including TaPR1, TaPR2, TaPR5, and
      TaWRKY45, where they repress histone acetylation. Moreover, reduced TaHOS15 or
      TaHDA6 transcript levels led to the decreased susceptibility to Bgt accompanied
      with the enhanced defense-related transcription under Bgt infection.
      Collectively, these results reveal that TaHOS15 functions in a histone
      deacetylase complex with TaHDA6 to fine-tune the defense response to Bgt in
      common wheat.

PMID- 30204900
TI  - Comment on: Conventional and biologic disease-modifying anti-rheumatic drugs for
      osteoarthritis: a meta-analysis of randomized controlled trials.

PMID- 30204901
TI  - Case report: tick-borne encephalitis (TBE) in a Belgian traveller returning from
      Germany.

PMID- 30204902
TI  - Investigating FlowSight(r) imaging flow cytometry as a platform to assess
      chemically induced micronuclei using human lymphoblastoid cells in vitro.
AB  - Use of imaging flow cytometry to assess induced DNA damage via the cytokinesis
      block micronucleus (CBMN) assay has thus far been limited to radiation dosimetry
      in human lymphocytes using high end, 'ImageStream X' series imaging cytometers.
      Its potential to enumerate chemically induced DNA damage using in vitro cell
      lines remains unexplored. In the present manuscript, we investigate the more
      affordable FlowSight(r) imaging cytometry platform to assess in vitro
      micronucleus (MN) induction in the human lymphoblastoid TK6 and metabolically
      competent MCL-5 cells treated with Methyl Methane Sulfonate (MMS) (0-5 ug/ml),
      Carbendazim (0-1.6 ug/ml), and Benzo[a]Pyrene (B[a]P) (0-6.3 ug/ml) for a period
      of 1.5-2 cell-cycles. Cells were fixed, and nuclei and MN were stained using the
      fluorescent nuclear dye DRAQ5TM. Image acquisition was carried out using a 20X
      objective on a FlowSight(r) imaging cytometer (Amnis, part of Merck Millipore)
      equipped with a 488 nm laser. Populations of ~20000 brightfield cell images,
      alongside DRAQ5TM stained nuclei/MN were rapidly collected (<=10 min). Single, in
      focus cells suitable for scoring were then isolated using the IDEAS(r) software.
      An overlay of the brightfield cell outlines and the DRAQ5 nuclear fluorescence
      was used to facilitate scoring of mono-, bi-, tri-, and tetra-nucleated cells
      with or without MN events and in context of the cytoplasmic boundary of the
      parent cell.To establish the potential of the FlowSight(r) platform, and to
      establish 'ground truth' cell classification for the supervised machine learning
      based scoring algorithm that represents the next stage of our project, the
      captured images were scored manually. Alongside, MN frequencies were also derived
      using the 'gold standard' light microscopy and manual scoring. A minimum of 3000
      bi-nucleated cells were assessed using both approaches. Using the benchmark dose
      approach, the comparability of genotoxic potency estimations for the different
      compounds and cell lines was assessed across the two scoring platforms as highly
      similar. This study therefore provides essential proof-of-concept that
      FlowSight(r) imaging cytometry is capable of reproducing the results of 'gold
      standard' manual scoring by light microscopy. We conclude that, with the right
      automated scoring algorithm, imaging flow cytometry could revolutionise the
      reportability and scoring throughput of the CBMN assay.

PMID- 30204903
TI  - An Open Trial of Morning Bright Light Treatment Among US Military Veterans with
      Chronic Low Back Pain: A Pilot Study.
AB  - Objective: To examine the feasibility, acceptability, and effects of a home-based
      morning bright light treatment on pain, mood, sleep, and circadian timing in US
      veterans with chronic low back pain. Design: An open treatment trial with a seven
      day baseline, followed by 13 days of a one-hour morning bright light treatment
      self-administered at home. Pain, pain sensitivity, mood, sleep, and circadian
      timing were assessed before, during, and after treatment. Setting: Participants
      slept at home, with weekly study visits and home saliva collections.
      Participants: Thirty-seven US veterans with medically verified chronic low back
      pain. Methods: Pain, mood, and sleep quality were assessed with questionnaires.
      Pain sensitivity was assessed using two laboratory tasks: a heat stimulus and an
      ischemia stimulus that gave measures of threshold and tolerance. Sleep was
      objectively assessed with wrist actigraphy. Circadian timing was assessed with
      the dim light melatonin onset. Results: Morning bright light treatment led to
      reduced pain intensity, pain behavior, thermal pain threshold sensitivity, post
      traumatic stress disorder symptoms, and improved sleep quality (P < 0.05). Phase
      advances in circadian timing were associated with reductions in pain interference
      (r = 0.55, P < 0.05). Conclusions: Morning bright light treatment is a feasible
      and acceptable treatment for US veterans with chronic low back pain. Those who
      undergo morning bright light treatment may show improvements in pain, pain
      sensitivity, and sleep. Advances in circadian timing may be one mechanism by
      which morning bright light reduces pain. Morning bright light treatment should be
      further explored as an innovative treatment for chronic pain conditions.

PMID- 30204904
TI  - Comment on: Conventional and biologic disease-modifying anti-rheumatic drugs for
      osteoarthritis: a meta-analysis of randomized controlled trials: reply.

PMID- 30204906
TI  - Cartilaginous Fishes Provide Insights into the Origin, Diversification, and
      Sexually Dimorphic Expression of Vertebrate Estrogen Receptor Genes.
AB  - Vertebrate estrogen receptors (ERs) perform numerous cell signaling and
      transcriptional regulatory functions. ERalpha (Esr1) and ERbeta (Esr2) likely
      evolved from an ancestral receptor that duplicated and diverged at the protein
      and cis-regulatory levels, but the evolutionary history of ERs, including the
      timing of proposed duplications, remains unresolved. Here we report on
      identification of two distinct ERs in cartilaginous fishes and demonstrate their
      orthology to ERalpha and ERbeta. Phylogenetic analyses place the ERalpha/ERbeta
      duplication near the base of crown gnathostomes (jawed vertebrates). We find that
      ERalpha and ERbeta from little skate (Leucoraja erinacea) and mammals share key
      subtype-specific residues, indicating conserved protein evolution. In contrast,
      jawless fishes have multiple non-orthologous Esr genes that arose by parallel
      duplications. Esr1 and Esr2 are expressed in subtype-specific and sexually
      dimorphic patterns in skate embryos, suggesting that ERs might have functioned in
      sexually dimorphic development before the divergence of cartilaginous and bony
      fishes.

PMID- 30204905
TI  - Nature and Cognitive Perception of 4 Different Breakfast Meals Influence Satiety
      Related Sensations and Postprandial Metabolic Responses but Have Little Effect on
      Food Choices and Intake Later in the Day in a Randomized Crossover Trial in
      Healthy Men.
AB  - Background: Regular breakfast consumption is associated with better health status
      and healthier food intake throughout the day, but this association is a complex
      interaction of several factors. Objective: This study aimed to investigate the
      effect of nutritional and cognitive-perceived characteristics of breakfast on
      metabolic and behavioral variables related to food intake. Methods: The study was
      a randomized, crossover, controlled trial, with 4 experimental conditions
      consisting of 3 iso-energetic breakfasts and 1 energy-free control meal.
      Breakfasts had similar nutritional profiles but differed for glycemic index (GI),
      glycemic load (GL), and perceived healthiness, satiety, palatability, or energy
      content. Fifteen healthy normal-weight men [means +/- SDs; age: 24 +/- 2 y; body
      mass index (BMI; kg/m2) 23.4 +/- 1.6] underwent each experimental condition in
      random order during 4 different weeks, separated by >=1-wk washout. On the third
      day of each intervention week, postprandial blood variables (with insulin as
      primary outcome), satiety ratings, and food intake during an ad libitum lunch
      consumed 4 h after breakfast (secondary outcomes) were measured for each
      experimental condition. Results: A main effect of time, treatment, and time *
      treatment was found for postprandial insulin, glucose, and nonesterified fatty
      acids (P < 0.001 for all) after having the 3 iso-energetic breakfasts or the
      energy-free control one. Postprandial satiety was similar for the 3 energy
      containing breakfasts, but higher when compared with the energy-free control (P <
      0.001). No difference in energy intake was observed for the ad libitum lunch,
      whereas prolonged breakfast skipping was compensated by an increase (around +10%)
      in the average energy intake during the rest of the day, resulting in no
      differences in the total daily energy intake among the 4 conditions. Conclusions:
      Although other advantages might exist for breakfasts based on low-GI/low-GL
      foods, our findings support the hypothesis that minor differences in nutritional
      and perceived characteristics of breakfast are of limited importance regarding
      medium-term energy intake in healthy men. This trial was registered at
      clinicaltrials.gov as BRNN-014 NCT02516956.

PMID- 30204907
TI  - Knee effusion volume assessed by magnetic resonance imaging and progression of
      knee osteoarthritis: data from the Osteoarthritis Initiative.
AB  - Objective: To examine whether baseline knee joint effusion volume and the change
      in effusion volume over 1 year are associated with cartilage volume loss,
      progression of radiographic OA (ROA) over 4 years and risk of total knee
      replacement over 6 years. Methods: This study included 4115 Osteoarthritis
      Initiative participants with knee joint effusion volume quantified by MRI at
      baseline. The change in effusion volume over 1 year was assessed. Cartilage
      volume loss and progression of ROA over 4 years were assessed using MRI and X-ray
      and total knee replacement over 6 years was assessed. Multiple linear regression
      and binary logistic regression were used for data analyses. Results: Baseline
      knee effusion volume (per 5 ml) was positively associated with a loss of medial
      and lateral cartilage volume [regression coefficient 0.13%/year (95% CI 0.10,
      0.17) and 0.13%/year (95% CI 0.10, 0.16), respectively, both P < 0.001],
      progression of ROA [odds ratio (OR) 1.28 (95% CI 1.20, 1.37), P < 0.001], and
      risk of knee replacement [OR 1.12 (95% CI 1.05, 1.20), P = 0.001]. A 5 ml
      increase in knee effusion volume over 1 year was positively associated with
      medial cartilage volume loss [regression coefficient 0.09%/year (95% CI 0.04,
      0.15), P = 0.001], progression of ROA [OR 1.21 (95% CI 1.11, 1.33), P < 0.001]
      and risk of knee replacement [OR 1.24 (95% CI 1.12, 1.37), P < 0.001].
      Conclusions: Knee joint effusion volume assessed from MRI provides a continuous
      and sensitive measure that was associated with cartilage volume loss, progression
      of ROA and risk of total knee replacement. It may provide a method to identify
      individuals with an inflammatory OA phenotype who are at higher risk of disease
      progression.

PMID- 30204909
TI  - Emergence of severe spondyloarthropathy-related entheseal pathology following
      successful vedolizumab therapy for inflammatory bowel disease.
AB  - Objectives: Vedolizumab (VDZ) blocks alpha4beta7 integrin and is licenced for the
      treatment of IBD. It has been associated with mild SpA-related features,
      including sacroiliitis and synovitis. Herein we report a series of cases
      demonstrating the emergence of severe SpA-associated enthesitis/osteitis
      following successful IBD therapy with VDZ. Methods: We evaluated 11 VDZ-treated
      patients with IBD across seven centres who developed severe active SpA and/or
      enthesopathy, with the aim of characterizing the VDZ-associated SpA or entheseal
      flares. Imaging features demonstrating particularly severe disease were recorded.
      Results: De novo SpA developed in 9 of 11 patients and flare of known SpA in 2
      patients, with 4 patients requiring hospitalization due to disease severity.
      Available data showed that one of seven cases were HLA-B27 positive. The median
      time from VDZ initiation to flare was 12 weeks, with IBD well controlled in 7 of
      10 patients (no data for 1 patient) at flare. Severe SpA enthesitis/osteitis was
      evident on MRI or US, including acute sacroiliitis (n = 5), extensive vertebral
      osteitis (n = 1), peri-facetal oedema (n = 1) and isolated peripheral enthesitis
      (n = 3). Due to arthritis severity, VDZ was discontinued in 9 of 11 patients and
      a change in therapy, including alternative anti-TNF, was initiated. Conclusion:
      Severe SpA, predominantly HLA-B27 negative, with osteitis/enthesitis may occur
      under successful VDZ treatment for IBD, including in subjects with prior anti-TNF
      therapy for intestinal disease.

PMID- 30204910
TI  - Down-regulation of p23 in normal lung epithelial cells reduces toxicities from
      exposure to benzo[a]pyrene and cigarette smoke condensate via an aryl hydrocarbon
      receptor-dependent mechanism.
AB  - The aryl hydrocarbon receptor (AHR) is a ligand-activated signaling molecule
      which controls tumor growth and metastasis, T cell differentiation, and liver
      development. Expression levels of this receptor protein is sensitive to the
      cellular p23 protein levels in immortalized cancer cell lines. As little as 30%
      reduction of the p23 cellular content can suppress the AHR function. Here we
      reported that down-regulation of the p23 protein content in normal, untransformed
      human bronchial tracheal epithelial cells to 56% of its content also suppresses
      the AHR protein levels to 59% of the wild-type content. This p23-mediated
      suppression of AHR is responsible for the suppression of (1) the ligand-dependent
      induction of the cyp1a1 gene transcription; (2) the benzo[a]pyrene- or cigarette
      smoke condensate-induced CYP1A1 enzyme activity and (3) the benzo[a]pyrene and
      cigarette smoke condensate-mediated production of reactive oxygen species.
      Reduction of the p23 content does not alter expression of oxidative stress genes
      and production of PGE2. Down regulation of p23 suppresses the AHR protein levels
      in two other untransformed cell types, namely human breast MCF-10A and mouse
      immune regulatory Tr1 cells. Collectively, down-regulation of p23 suppresses the
      AHR protein levels in normal and untransformed cells and can in principle protect
      our lung epithelial cells from AHR-dependent oxidative damage caused by exposure
      to agents from environment and cigarette smoking.

PMID- 30204912
TI  - Coexistence of plantar calcaneal spurs and plantar fascial thickening in
      individuals with plantar heel pain.
AB  - Objectives: To examine associations between plantar calcaneal spurs, plantar
      fascia thickening and plantar heel pain (PHP), and to determine whether
      tenderness on palpation of the heel differentiates between these presentations.
      Methods: Adults aged ?50 years registered with four general practices were mailed
      a Health Survey. Responders reporting foot pain within the last 12 months
      underwent a detailed clinical assessment. PHP in the past month was documented
      using a foot manikin. Plantar calcaneal spurs were identified from weight-bearing
      lateral radiographs and plantar fascia thickening (defined as >4 mm) from
      ultrasound. Tenderness on palpation of the plantar fascia insertion was
      documented. Associations between these factors and PHP were explored using
      generalized estimating equations. Results: Clinical and radiographic data were
      available from 530 participants (296 women, mean [s.d.] age 64.9 [8.4] years),
      117 (22.1%) of whom reported PHP. Plantar calcaneal spurs and plantar fascia
      thickening were identified in 281 (26.5%) and 501 (47.3%) feet, respectively, but
      frequently coexisted (n = 217, 20.4%). Isolated plantar calcaneal spurs were rare
      (n = 64, 6.0%). Participants with PHP were more likely to have a combination of
      these features compared with those without PHP (odds ratio 2.16, 95% CI 1.24,
      3.77, P = 0.007). Tenderness on palpation of the heel was not associated with
      plantar calcaneal spurs or plantar fascia thickening, either in isolation or in
      combination, in those with PHP. Conclusion: Plantar calcaneal spurs and plantar
      fascial thickening are associated with PHP, but frequently coexist. Tenderness on
      palpation of the heel does not appear to differentiate between clinical
      presentations of PHP.

PMID- 30204913
TI  - Evaluating Mode of Action of Acrolein Toxicity in an In Vitro Human Airway Tissue
      Model.
AB  - Acrolein is a reactive unsaturated aldehyde and is found at high concentrations
      in both mainstream and side-stream tobacco smoke. Exposure to acrolein via
      cigarette smoking has been associated with acute lung injury, chronic obstructive
      pulmonary diseases (COPDs), and asthma. In this study, we developed an in vitro
      treatment strategy that resembles the inhalation exposure to acrolein experienced
      by smokers and systematically examined the adverse respiratory effects induced by
      the noncytotoxic doses of acrolein in a human airway epithelial tissue model. A
      single 10-min exposure to buffered saline containing acrolein significantly
      induced oxidative stress and inflammatory responses, with changes in protein
      oxidation and GSH depletion occurring immediately after the treatment whereas
      responses in inflammation requiring a manifestation time of at least 24 h.
      Repeated exposure to acrolein for 10 consecutive days resulted in structural and
      functional changes that recapitulate the pathological lesions of COPD, including
      alterations in the beating frequency and structures of ciliated cells, inhibition
      of mucin expression and secretion apparatus, and development of squamous
      differentiation. Although some of the early responses caused by acrolein exposure
      were reversible after a 10-day recovery, perturbations in the functions and
      structures of the air-liquid-interface (ALI) cultures, such as mucin production,
      cilia structures, and morphological changes, failed to fully recover over the
      observation period. Taken together, these findings are consistent with its mode
      of action that oxidative stress and inflammation have fundamental roles in
      acrolein-induced tissue remodeling. Furthermore, these data demonstrate the
      usefulness of analytical methods and testing strategy for recapitulating the key
      events in acrolein toxicity using an in vitro model.

PMID- 30204911
TI  - Physical pain recruits the nucleus accumbens during social distress in borderline
      personality disorder.
AB  - Patients with borderline personality disorder (BPD) often engage in dangerous
      self-injurious behaviors (SIBs) as a maladaptive technique to decrease heightened
      feelings of distress (e.g. negative feelings caused by social exclusion). The
      reward system has recently been proposed as a plausible neural substrate, which
      may influence the interaction between social distress and physical pain
      processing in patients that engage in SIBs. Using functional magnetic resonance
      imaging (fMRI) in 20 adult BPD patients with a history of SIBs and 23 healthy
      controls (HCs), we found a hyper-activation of the nucleus accumbens (NAcc) and
      amygdala when painful stimuli were presented to BPD patients (but not HCs) in a
      state of heightened distress, induced via social exclusion. This differential
      NAcc activity was mediated by anxious attachment style, which is a key
      developmental feature of the disorder. Altogether, these results suggest a neural
      mechanism underlying the pathophysiology of SIBs in these patients, which is
      likely reinforced via the reward system.

PMID- 30204914
TI  - Non-halophilic endophytes associated with the euhalophyte Arthrocnemum
      macrostachyum and their plant growth promoting activity potential.
AB  - Numerous microbial taxa establish natural relations with plants, and especially
      endophytes can be relevant in the development and growth promotion of their host.
      In this work, we explore the diversity of non-halophilic microorganisms
      inhabiting the endosphere of the halophyte Arthrocnemum macrostachyum. A total of
      1045 isolates were recovered using standard non-saline media, which clustered
      into 22 operational phylogenetic units (OPUs) including 7 putative new species
      and 13 OPUs not previously detected as endophytes. The more abundant isolates
      corresponded to close relatives of Kushneria indalinina/K. marisflavi,
      Providencia rettgeri, Pseudomonas zhaodongensis and Bacillus safensis, which made
      up to ~ 62% of the total isolates. We also isolated OPUs not detected by the
      culture-independent approach reinforcing the need of culturing to reveal the
      microbial diversity associated with plants. Additionally, the plant growth
      promoting activity was evaluated by representative strains of the more abundant
      OPUs (total = 94 strains) including also some previously isolated halophiles from
      the same plants. Under both saline and non-saline conditions, some strains
      principally those affiliated to Paenibacillus borealis, Staphylococcus equorum,
      Salinicola halophilus and Marinococcus tarijensis, presented growth promoting
      activity in Arabidopsis thaliana, which was evaluated as an increment of weight
      and root length.

PMID- 30204915
TI  - PIM-1 kinase is a novel regulator of proinflammatory cytokine-mediated responses
      in rheumatoid arthritis fibroblast-like synoviocytes.
AB  - Objectives: This study investigated the expression of proviral-integration site
      for Moloney murine leukaemia virus (PIM) -1 kinase in RA synovium and RA
      fibroblast-like synoviocytes (FLSs) along with its impact on RA-FLS
      aggressiveness. Methods: The expression of PIM kinases was assessed in synovial
      tissues by immunohistochemistry and double IF. After PIM-1 inhibition using
      either small-interfering RNA or the chemical inhibitor AZD1208, we performed
      proliferation and migration assays and measured the levels of MMPs and IL-6
      released from RA-FLSs under stimulation with proinflammatory cytokines (TNF
      alpha, S100A4 and IL-6/soluble IL-6 receptor). Additionally, PIM-1-associated
      downstream signalling pathways were analysed by immunoblotting. Results: Three
      isoforms of PIM kinases were immunodetected in the synovial tissues from patients
      with RA or OA. Specifically, PIM-1 and PIM-3 were upregulated in RA synovium and
      PIM-1 was expressed in T cells, macrophages and FLSs. Additionally, upon
      stimulation of RA-FLSs with TNF-alpha, S100A4 and IL-6/sIL-6R, PIM-1 and PIM-3,
      but not PIM-2, were significantly inducible. Moreover, PIM-1 knockdown or AZD1208
      treatment significantly suppressed basal or cytokine-induced proliferation and
      migration of RA-FLS and the secretion of MMPs from stimulated RA-FLSs. PIM-1
      knockdown significantly affected the phosphorylation levels of extracellular
      signal-regulated kinase and cAMP responsive element binding protein in RA-FLSs.
      Conclusion: PIM-1 was upregulated in RA synovial tissues and RA-FLSs and its
      inhibition significantly reduced the proliferation, migration and MMP production
      of RA-FLSs in vitro. These findings suggest PIM-1 as a novel regulator of the
      aggressive and invasive behaviour of RA-FLSs and indicate its potential as a
      target for RA treatment.

PMID- 30204917
TI  - Body Protein Reserves Sustain Maternal Performance in Early Lactation but Dietary
      Protein Is Necessary to Maintain Performance and Immune Responses to
      Nippostrongylus brasiliensis in Lactating Rats.
AB  - Background: It has been shown that dietary protein supplementation during
      lactation boosts immunity in Nippostrongylus brasiliensis-infected periparturient
      rats. It is not known whether body protein reserves accumulated during gestation
      have a similar effect during lactation. Objective: This study aimed to quantify
      the impact of body protein reserves and dietary protein supplementation on
      maternal performance and immune responses to N. brasiliensis during lactation.
      Methods: Multiparous female Sprague-Dawley rats were administered a primary
      infection of N. brasiliensis before mating and were restriction-fed either 60 g
      [low-protein diet gestation (Lge)] or 210 g [high-protein diet gestation (Hge)]
      crude protein (CP) per kilogram of dry matter (DM) until parturition. From
      parturition onward, dams were restriction-fed either 100 g [low-protein diet
      lactation (Lla)] or 300 g [high-protein diet lactation (Hla)] CP per kilogram of
      DM, generating 4 different dietary treatments. A subset of rats was sampled
      before parturition; postparturition, dams were secondarily infected with N.
      brasiliensis and samples were collected at days 5 and 11 postparturition.
      Results: Maternal performance until parturition, as measured by pup weight, was
      better in Hge rats than in Lge rats [Lge: 4.84 g; Hge: 6.15 g; standard error of
      the difference (SED): 0.19]. On day 11, pup weights of dams with reduced protein
      reserves fed protein during lactation (Lge-Hla; 20.28 g) were higher than their
      counterparts from Hge-Lla dams (17.88 g; SED: 0.92). Worm counts were
      significantly different between Lge-Lla-fed (253; 95% CI: 124, 382) and Hge-Hla
      fed (87; 95% CI: 22, 104) dams on day 11 (P = 0.024). The expression of splenic
      interleukin 13 (Il13) and arachidonate 15-lipoxygenase (Alox15) was significantly
      higher (P < 0.05) in Hge-Hla dams compared with Lge-Lla dams on day 5.
      Conclusions: Although protein reserves were adequate to maintain maternal
      performance in the early stage of lactation in dams infected with N.
      brasiliensis, they were not adequate to maintain maternal performance and
      effective immune responses at later stages. Dietary protein supplementation was
      required to achieve this.

PMID- 30204916
TI  - Using a Community-Based Early Childhood Development Center as a Platform to
      Promote Production and Consumption Diversity Increases Children's Dietary Intake
      and Reduces Stunting in Malawi: A Cluster-Randomized Trial.
AB  - Background: Children in Malawi face nutritional risks related to low-quality
      diets and chronic malnutrition. Objective: This study evaluated the impact of a 1
      y early childhood development (ECD) center-based agriculture and nutrition
      intervention aimed at improving household production diversity, maternal
      knowledge on child nutrition and feeding practices, and children's diets and
      anthropometric measures. Methods: A longitudinal cluster-randomized controlled
      trial was implemented in 60 community-based childcare centers (CBCCs), covering
      1248 preschool children (aged 36-72 mo) and 304 younger siblings (aged 6-24 mo).
      CBCCs were randomly assigned to 1) a control group providing the Save the
      Children's ECD program or 2) a treatment group providing a standard ECD program
      with additional activities to improve nutritious food production and behavior
      change communication to improve diets and care practices for young children.
      Primary outcomes were household production and production diversity, preschooler
      enrollment and attendance, and dietary intake measured by quantitative 24-h
      recall and minimum diet diversity for younger siblings. Secondary outcomes
      included anthropometric measures for preschoolers and younger siblings, child
      development scores for preschoolers, and women's asset ownership and time use
      (the latter 2 are not discussed in this article). We used difference-in
      difference (DID) estimates to assess impacts. Results: Compared with the control
      group, preschool children in the intervention group had greater increases in
      nutrient intakes and in dietary diversity. No impacts on anthropometric measures
      were seen in preschoolers. Younger siblings in the intervention group had greater
      increases in height-for-age z scores than did children in the control group (DID:
      0.44; P < 0.05) and greater reductions in the prevalence of stunting (DID: -17
      percentage points; P < 0.05). The plausibility of the impact on growth in younger
      siblings was supported by effects along program impact pathways, including
      production of nutritious foods, caregiver knowledge, and dietary diversity.
      Conclusion: Implementing an integrated agriculture and nutrition intervention
      through an ECD platform benefited children's diets and reduced stunting among
      younger siblings of targeted preschoolers. This trial was registered on the
      ISRCTN registry as ISCRCTN96497560.

PMID- 30204918
TI  - Low Self-Esteem for Physical Appearance Mediates the Effect of Body Mass Index on
      Smoking Initiation Among Adolescents.
AB  - Objective: Adolescence is a period during which youth may begin experimenting
      with substances. Youth with overweight or obesity may be at increased risk for
      substance use, including cigarette smoking. Understanding the associations
      between smoking and excess weight and the pathways associated with increased
      likelihood for smoking initiation is of particular importance given the increased
      risk for negative health outcomes associated with each. Methods: Using
      longitudinal panel data from 1,023 middle school youth (baseline age M = 12.5,
      52% female), we tested whether smoking initiation was concurrently and
      prospectively predicted by self-reported body mass index (BMI) and whether self
      esteem for physical appearance (SEPA) mediated the effect of BMI on risk of early
      initiation. Results: BMI predicted smoking initiation concurrently and
      prospectively in unadjusted models. In adjusted models, SEPA mediated the effects
      of BMI on smoking initiation. Bootstrapped mediation results indicated that the
      positive relationship between BMI and subsequent smoking initiation was
      significantly mediated by lower SEPA (B =.10, 95% confidence interval [0.01,
      0.22]). Conclusions: Adolescents who have overweight or obesity are more likely
      to feel negatively about their appearance and bodies, and this negative
      perception may result in experimentation with cigarettes. Cigarettes may be used
      by youth with overweight or obesity in an effort to manage weight, to cope with
      low self-esteem or for other reasons. Future research should explore the motives
      and psychosocial context of smoking initiation among adolescents with
      overweight/obesity further (e.g., with whom they first try smoking, perceived
      benefits of smoking).

PMID- 30204919
TI  - Multisite Randomized Clinical Trial Evaluating an Online Self-Management Program
      for Adolescents With Juvenile Idiopathic Arthritis.
AB  - Objective: To determine the efficacy in improving pain and health-related quality
      of life (HRQOL) of an online self-management program for adolescents with
      juvenile idiopathic arthritis (JIA). Methods: Youth ages 12-18 years with JIA
      were recruited from 10 rheumatology clinics across the United States and
      randomized to complete an online self-management program (n = 144) or an online
      disease education program (n = 145). Participants in the self-management group
      worked through multimedia-based modules comprising psychoeducation, training in
      cognitive-behavioral coping skills and stress management, and other self
      management topics over a 12-week period. Participants in the control group viewed
      a series of preselected quality educational websites about JIA over the same
      interval. Online content for both groups was made available in English and
      Spanish to facilitate inclusion of Hispanic participants. Blinded assessment of
      main outcomes (pain intensity, pain interference, and HRQOL) and process outcomes
      (disease knowledge, self-efficacy, pain coping, and emotional adjustment)
      occurred at baseline, posttreatment, and at 6- and 12-month postrandomization
      follow-up visits. Results: Participants on average demonstrated significant
      improvements over the study period in the main outcomes, with no significant
      group differences in the degree of improvement. Effect sizes for these
      improvements were small. The amount of improvement in self-efficacy, emotional
      avoidance coping, disease knowledge, and emotional functioning in part predicted
      improvement in pain and HRQOL outcomes. Conclusions: Primarily self-directed
      online self-management training and online disease education comparably and
      modestly improve pain and HRQOL in youth with JIA.

PMID- 30204920
TI  - Are Invasive Procedures Effective for Chronic Pain? A Systematic Review.
AB  - Objective: To assess the evidence for the safety and efficacy of invasive
      procedures for reducing chronic pain and improving function and health-related
      quality of life compared with sham (placebo) procedures. Design: Systematic
      review with meta-analysis. Methods: Studies were identified by searching multiple
      electronic databases, examining reference lists, and communicating with experts.
      Randomized controlled trials comparing invasive procedures with identical but
      otherwise sham procedures for chronic pain conditions were selected. Three
      authors independently extracted and described study characteristics and assessed
      Cochrane risk of bias. Two subsets of data on back and knee pain, respectively,
      were pooled using random-effects meta-analysis. Overall quality of the literature
      was assessed through Grading of Recommendations, Assessment, Development, and
      Evaluation. Results: Twenty-five trials (2,000 participants) were included in the
      review assessing the effect of invasive procedures over sham. Conditions included
      low back (N = 7 trials), arthritis (4), angina (4), abdominal pain (3),
      endometriosis (3), biliary colic (2), and migraine (2). Thirteen trials (52%)
      reported an adequate concealment of allocation. Fourteen studies (56%) reported
      on adverse events. Of these, the risk of any adverse event was significantly
      higher for invasive procedures (12%) than sham procedures (4%; risk difference =
      0.05, 95% confidence interval [CI] = 0.01 to 0.09, P = 0.01, I2 = 65%). In the
      two meta-analysis subsets, the standardized mean difference for reduction of low
      back pain in seven studies (N = 445) was 0.18 (95% CI = -0.14 to 0.51, P = 0.26,
      I2 = 62%), and for knee pain in three studies (N = 496) it was 0.04 (95% CI = 
      0.11 to 0.19, P = 0.63, I2 = 36%). The relative contribution of within-group
      improvement in sham treatments accounted for 87% of the effect compared with
      active treatment across all conditions. Conclusions: There is little evidence for
      the specific efficacy beyond sham for invasive procedures in chronic pain. A
      moderate amount of evidence does not support the use of invasive procedures as
      compared with sham procedures for patients with chronic back or knee pain. Given
      their high cost and safety concerns, more rigorous studies are required before
      invasive procedures are routinely used for patients with chronic pain.

PMID- 30204922
TI  - Intrauterine Pressure During Hysteroscopic Morcellation: A Comparison of Three
      Commercially-Available Devices.
AB  - STUDY OBJECTIVE: Our objective was to compare intrauterine pressures during
      resection and aspiration modes among three types of commercially-available
      hysteroscopic morcellators. DESIGN: This was a benchtop study (Canadian Task
      Force level II-1). This study cannot feasibly and ethically be done in-vivo, so
      an ex-vivo study design was chosen. SETTING: A silicone uterine model was
      attached to a manometer via tubing, with the tip inside the cavity to allow for
      intracavity pressure measurements. Each hysteroscopic morcellator was then
      introduced, and intracavity pressures were recorded every one to two seconds in
      three modes (static, resection, and aspiration) and at three set point pressures
      (45, 85, and 125 mmHg). PATIENTS: No human subjects were involved in this study.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were a total of 4,872
      pressure measurements during this study across the three devices, over the three
      modes, and at the three set point pressures combined. Using mixed-effects linear
      regression, the mean observed intracavity pressure was not greater than the set
      pressure for each of the three devices. This result held true in both aspiration
      and resection modes. In our statistical models, the coefficient on the terms
      representing the interaction between device and time were not statistically
      significant in either resection or aspiration modes. This indicates that,
      statistically, the change in intracavity pressure over time was not significantly
      different across the three devices. CONCLUSION: In this first of its kind head-to
      head benchtop study, we found that all three commercially-available hysteroscopic
      morcellators appear to be similar to each other in terms of their abilities to
      maintain intracavity pressure below the set pressure, which is important in
      avoiding intravasation in-vivo. These findings are important because many
      gynecologists do not have the ability to choose between the three available
      devices on the market at their institution.

PMID- 30204921
TI  - Corn Oil Lowers Plasma Cholesterol Compared with Coconut Oil in Adults with Above
      Desirable Levels of Cholesterol in a Randomized Crossover Trial.
AB  - Background: Few trials have examined the effects of coconut oil consumption in
      comparison with polyunsaturated fatty acid-rich oils such as corn oil. Objective:
      This trial assessed the effects of consuming foods made with corn oil compared
      with coconut oil on lipids, glucose homeostasis, and inflammation. Methods: This
      was a preliminary randomized crossover study of men (n = 12) and women (n = 13)
      with a mean age of 45.2 y, mean body mass index (in kg/m2) of 27.7, fasting LDL
      cholesterol >=115 mg/dL and <190 mg/dL, and triglycerides (TGs) <=375 mg/dL.
      Subjects consumed muffins and rolls providing 4 tablespoons (~54 g) per day of
      corn oil or coconut oil as part of their habitual diets for 4 wk, with a 3-wk
      washout between conditions. Fasting plasma lipids and high-sensitivity C-reactive
      protein (hs-CRP) and glucose metabolism were assessed via an intravenous glucose
      tolerance test at baseline and 15 and 29 d of treatment. Responses were compared
      between treatments by ANCOVA. Results: Median baseline concentrations of LDL
      cholesterol, non-HDL cholesterol, total cholesterol (total-C), HDL cholesterol,
      total-C:HDL cholesterol, and TGs were 123, 144, 188, 46.0, 4.21, and 92.5 mg/dL,
      respectively. Changes from baseline for corn oil and coconut oil conditions,
      respectively, were: LDL cholesterol (primary outcome; -2.7% compared with +4.6%),
      non-HDL cholesterol (-3.0% compared with +5.8%), total-C (-0.5% compared with
      +7.1%), HDL cholesterol (+5.4% compared with +6.5%), total-C:HDL cholesterol (
      4.3% compared with -3.3%), and TGs (-2.1% compared with +6.0%). Non-HDL
      cholesterol responses were significantly different between corn and coconut oil
      conditions (P = 0.034); differences between conditions in total-C and LDL
      cholesterol approached significance (both P = 0.06). Responses for hs-CRP and
      carbohydrate homeostasis parameters did not differ significantly between diet
      conditions. Conclusions: When incorporated into the habitual diet, consumption of
      foods providing ~54 g of corn oil/d produced a more favorable plasma lipid
      profile than did coconut oil in adults with elevated cholesterol. This trial was
      registered at clinicaltrials.gov as NCT03202654.

PMID- 30204923
TI  - Ultrasound-Guided Calcium Debridement of the Shoulder Joint: A Case Series.
AB  - OBJECTIVE: Our purpose was to assess the outcomes of those who underwent an
      ultrasound-guided debridement of the deposits. Specifically, we analyzed: (1)
      function; (2) pain; (3) activity level; (4) patient satisfaction; and (5)
      complications. MATERIALS AND METHODS: A review of patients who underwent an
      ultrasound-guided debridement of calcific deposits about their shoulder joint
      between 2005 and 2015 was performed. Our final cohort consisted of 38 patients
      with a mean age of 53 years (range, 35 to 62 years)-11 men and 27 women-and a
      mean follow up of 32 months (range, 12 to 53 months). Functional outcomes,
      activity level, and pain level were assessed using the Disabilities of Arm,
      Shoulder, and Hand (DASH) scale, the University of Southern California (UCLA)
      activity scale, and the Visual Analog Scale (VAS). Additionally, patients were
      asked if they were satisfied with the outcomes of their procedure. All medical
      records were assessed for potential complications from this procedure. RESULTS:
      Excellent outcomes were achieved. The mean DASH score improved from 21 to 10
      points (p=0.0001). Additionally, mean UCLA score increased from 2 to 7 points
      (p=0.0001). Furthermore, the mean reported VAS improved from 8 to 1.6 (p=0.0001).
      Ninety-seven percent of patients reported being satisfied. There were no reported
      complications in our cohort. CONCLUSION: We found that this procedure can result
      in effective pain relief and prevent or delay the need for more invasive
      procedures. Future studies should evaluate the role of calcium deposit size in
      the outcomes of those who undergo debridement.

PMID- 30204924
TI  - Backpack Forces on the Spine.
AB  - OBJECT: Backpacks are standard load carriers for people of all ages, especially
      school children and the military. Previous studies have described the impact of
      the forces exerted by backpacks on load distribution, back pain, and gait. The
      objective of this study was to use finite element analysis (FEA) to assess the
      effects of incremental weights in a backpack on the spine. METHODS: To assess the
      forces experienced by the spine under the incremental addition of weight to a
      backpack, we performed a finite element simulation using commercially available
      'BodyParts3D/Anatomography' data, which were imported into FEA software. We
      studied two different scenarios: 1) a regular backpack with incrementally placed
      weights using both shoulder straps with the spine in a neutral position, and 2) a
      regular backpack with incrementally placed weights using both shoulder straps
      with the spine tilted forward 20 degrees. The spine model was physiologically
      accurate. RESULTS: For all of the added weights examined (1-100 pounds; 0.45
      45.36 kg), the force experienced by the neutral spine was 7.2-fold the added
      weight. For the 20 degrees-forward posture, this value rose to 11.6-fold.
      CONCLUSIONS: These findings should help to clarify the forces experienced by the
      spine due to objects in a backpack. For example, this should help spinal surgeons
      to better understand the tremendous importance of sagittal plane alignment in
      planning their surgical reconstructions.

PMID- 30204925
TI  - Surgical Treatment of Sacral Chordoma: En Bloc Resection with Negative Margins is
      a Determinant of the Long-Term Outcome.
AB  - STUDY DESIGN: Retrospective case series. OBJECTIVE: To report the outcome of a
      series of patients with sacral chordoma who were surgically treated at a single
      center. SUMMARY: Chordomas are low-grade malignant tumors that arise from
      remnants of the notochord. They are most often found in the sacrum, spine and
      skull-base. These tumors have a slow clinical evolution and may eventually
      metastasize, even after adequate treatment. Rarely, they can dedifferentiate into
      high-grade sarcomas. Traditionally, chordomas were considered to be resistant to
      chemotherapy and standard radiation therapy. However, recently, adrotherapy has
      been shown to be effective for local and systemic control of the disease. In this
      study, clinical outcomes and local and systemic recurrence were reviewed to
      identify prognostic factors for local and systemic control. METHODS: Thirty-three
      patients with sacral chordoma (19 males, 14 females; median age 61 y, range 43
      80) who were surgically treated at our institution between 1994 and 2015 were
      reviewed. In 24 patients, resection was performed above S2. No patients received
      pre-operative radiotherapy (RT). Three cases received RT (carbon ion therapy) as
      treatment for local recurrence. Wide (R0) surgical margins were achieved in 17
      patients, marginal (R1) margins in 14 patients and intralesional (R2) margins in
      2 patients. RESULTS: At a median follow-up of 53 months (range 0-198), 19
      patients were continuously disease-free, 6 were disease-free after local
      recurrence (5) or metastases (1), 3 were alive with disease (2 local recurrence
      and 1 metastasis), 4 were dead of disease (1 patient died intraoperatively) and 1
      was dead of another cause. Local recurrence was observed in 9 cases (27%); all 9
      were treated surgically and 3 received carbon ion therapy after surgical
      intralesional excision. Overall survival at 10 years was 86.6%. Local recurrence
      free survival at 10 years was 51%. A statistical analysis confirmed the
      importance of negative surgical margins (R0) to achieve local control of the
      disease (p = 0.0007). High resections (above S2) were associated with lower
      survival and higher risk of local recurrence. CONCLUSION: Surgical en bloc
      resection is the primary treatment for sacral chordoma. Carbon ion therapy is
      used when it is difficult to obtain wide surgical margins. Due to morbidity and
      the disabling sequelae of surgery, adrotherapy may be considered an alternative
      to high (above S2-S3) sacral chordoma resections.

PMID- 30204926
TI  - Blended Learning Methods for Surgical Education.
AB  - The emergence and maturation of the concept of blended learning in public and
      military education may prove equally valuable in CME surgical education and
      training. Creating a learner-centric environment in which multiple modes of
      education are encouraged, available, integrated, and accredited can increase the
      level of competence achieved in CME courses. This paper defines a framework for
      blended surgical training using principles developed for the military and it is
      applied in courses at a major post-graduate surgical education center.

PMID- 30204927
TI  - Prevention of Parastomal Hernia.
AB  - Parastomal hernia (PSH), defined as an incisional hernia at the abdominal wall
      defect resulting from stoma formation, is a frequent complication of enterostomy
      (ileostomy and jejunostomy), colostomy, and urostomy. A growing body of evidence
      supports the use of prophylactic mesh at the time of stoma creation to prevent
      the development of PSH. In particular, the use of permanent mesh has been
      supported in the creation of an end colostomy, and prophylactic mesh has been
      studied for use in other types of stoma. Permanent mesh materials used for PSH
      prophylaxis include polypropylene, polyester, polytetrafluoroethylene, and
      composite prosthetics. Despite the appeal of biologic and bioabsorbable materials
      in an operative field that poses a potentially higher risk of infection, there is
      insufficient evidence to support their use in primary PSH prevention. Two
      dimensional meshes are usually cut to contain a keyhole through which the bowel
      passes, and may be placed in the sublay/retrorectus, intraperitoneal, or
      preperitoneal position. Alternative techniques include placement of a non-keyhole
      mesh in a position similar to that of a Sugarbaker PSH repair or use of a
      circular stapler fired through the abdominal wall fascia and mesh simultaneously,
      fixing both together. Three-dimensional mesh devices, including the Prolene(r)
      and Ultrapro(r) Hernia Systems (PHS/UHS) (Ethicon US, LLC, Somerville, NJ), have
      been studied for use in PSH prevention. Novel, specialized devices such as the
      Koring? (Koring AG, Basel, Switzerland) stoma mesh have been designed
      specifically for primary PSH prevention. While the benefits of mesh prophylaxis
      have been established, further evidence is needed to identify the optimal
      materials and technique for PSH prevention in a variety of patients and settings.
      The purpose of this report is to provide an overview of the operative techniques
      and evidence supporting prophylaxis of parastomal hernias.

PMID- 30204928
TI  - Favorable Management of Low Colorectal Anastomotic Leakage with Transanal
      Conventional and Endoscopic Drainage (GelPOINT(r) Path Transanal Access
      Platform).
AB  - OBJECTIVE: We describe our experience with transanal-laparoscopic treatment of
      anastomotic leakage. SUMMARY OF BACKGROUND DATA: Anastomotic leakage leads to
      high mortality rates, morbidity, a complicated post-operative course and
      increased cost. The management of low anastomotic leakage after anterior
      resection of rectal cancer is not standardized. METHODS: This was a retrospective
      cohort study based on prospectively collected data. Among patients who underwent
      anterior resection for rectal cancer in our division between January 2014 and
      October 2017, 14 developed colorectal or colo-anal anastomotic leakage and
      underwent reoperation with a transanal approach. Data regarding patient
      demographics, reoperative outcomes, morbidity, length of hospital stay,
      mortality, leak closure and long-term outcomes are presented. RESULTS: In all
      patients, anastomotic healing was confirmed by radiology. No perioperative
      complications were detected. One patient presented anastomotic stricture after 20
      months, which was successfully treated with dilatation. CONCLUSIONS: There is
      little information available on the management of anastomotic leakage after
      anterior resection for rectal cancer. Although more studies are needed to
      standardize patient selection criteria and evaluate the long-term outcome of
      these procedures, minimally invasive transanal conventional and laparoscopic
      anastomotic leak repair is a feasible and safe surgical option that can often
      avoid the need for anastomotic takedown and stoma formation.

PMID- 30204929
TI  - Latest Advances in Transcatheter Cardiac Valvular Treatment.
AB  - When the original monograph on valvular prostheses was published in Surgical
      Technology International, back in 1993, transcatheter technology had not yet been
      invented. These techniques have been gradually revealed in subsequent issues.
      When we first considered writing a paper that described both surgical and
      transcatheter prosthesis, we realized that such a combined paper would be
      impractically large. Therefore, we decided to split our survey into more than one
      paper. This paper seeks to address the paucity of information available regarding
      transcatheter aortic valve implantation (TAVI) and similar devices. This
      publication may serve as a reference point for critically organizing information
      on an evolving topic. The following article deals with the large number of
      transcatheter devices related to valvular and ventricular pathologies: TAVI for
      the aortic and mitral valves, with a focus on indications, techniques and
      complications, as well as specific aortic devices, and devices to treat mitral
      regurgitation with non-conventional access. Every effort has been made to make
      the content relevant and up-to-date, which proved to be particularly challenging
      due to the continuous technological evolution which characterizes this field.

PMID- 30204930
TI  - Dynamic Combinatorial Chemistry: A New Methodology Comes of Age.
AB  - Dynamic combinatorial chemistry (DCC) has repeatedly proven to be an effective
      approach to generate directed ligand libraries for macromolecular targets. In the
      absence of an external stimulus, a dynamic library forms from reversibly reacting
      building blocks and reaches a stable thermodynamic equilibrium. However, upon
      addition of a macromolecular host which can bind and stabilize certain components
      of the library, the equilibrium composition changes and induces an evolution-like
      selection and enrichment of high-affinity ligands. A valuable application of this
      so-called target-directed DCC (tdDCC) is the identification of potent ligands for
      pharmacologically relevant targets. Over time, the term tdDCC has been applied to
      describe a number of different experimental set-ups, leading to some ambiguity
      concerning its definition. This article systematically classifies known
      procedures for tdDCC and related approaches, with a special focus on the methods
      used for analysis and evaluation of experiments.

PMID- 30204932
TI  - Testing the intermittent upwelling hypothesis: Reply.
AB  - We evaluated the Intermittent Upwelling Hypothesis (IUH) in Shanks and Morgan
      (Shanks and Morgan 2018), henceforth S&M. We presented five expectations, which
      must be true if the hypothesis is correct. We tested each of these expectations
      against available published results and, as part of this analysis, we reanalyzed
      data from Broitman et al. (Broitman et al. 2008). We concluded that available
      data do not support any of the five expectations and, hence, the IUH was not
      supported. Menge and Menge (this issue, henceforth M&M2) dispute our conclusions,
      and here we respond to their comments. This article is protected by copyright.
      All rights reserved.

PMID- 30204931
TI  - CCBE1 is required for coronary vessel development and proper coronary artery stem
      formation in the mouse heart.
AB  - BACKGROUND: Proper coronary vasculature development is essential for late
      embryonic and adult heart function. The developmental regulation of coronary
      embryogenesis is complex and includes the coordinated activity of multiple
      signaling pathways. CCBE1 plays an important role during lymphangiogenesis,
      enhancing VEGF-C signaling, which is also required for coronary vasculature
      formation. However, whether CCBE1 plays a similar role during coronary
      vasculature development is still unknown. Here, we investigate the coronary
      vasculature development in Ccbe1 mutant embryos. RESULTS: We show that Ccbe1 is
      expressed in the epicardium, like Vegf-c, and also in the sinus venosus (SV) at
      the stages of its contribution to coronary vasculature formation. We also report
      that absence of CCBE1 in cardiac tissue inhibited coronary growth that sprouts
      from the SV endocardium at the dorsal cardiac wall. This disruption of coronary
      formation correlates with abnormal processing of VEGF-C propeptides, suggesting
      VEGF-C-dependent signaling alteration. Moreover, Ccbe1 loss-of-function leads to
      the development of defective dorsal and ventral intramyocardial vessels. We also
      demonstrate that Ccbe1 mutants display delayed and mispatterned coronary artery
      (CA) stem formation. CONCLUSIONS: CCBE1 is essential for coronary vessel
      formation, independent of their embryonic origin, and is also necessary for
      peritruncal vessel growth and proper CA stem patterning. Developmental Dynamics
      247:1135-1145, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 30204933
TI  - Molecular basis and mechanism underlying the insecticidal activity of venoms and
      toxins from Latrodectus spiders.
AB  - Latrodectus species are among the most venomous of spiders, with abundant toxic
      proteinaceous components in their venomous glands and other tissues, as well as
      their eggs. To date, several proteinaceous toxins with insecticidal potential,
      including alpha-insectotoxin and delta-insectotoxin, two of the most potent known
      insecticidal toxins, have been purified and characterized by comprehensively
      utilizing conventional biochemical techniques. This has greatly enhanced our
      knowledge of the molecular basis and mechanism of action of their toxicity.
      Application of proteomic and transcriptomic techniques further revealed the
      synergistic action of multiple Latrodectus proteinaceous toxins and toxin-like
      components. Insecticidal toxins from Latrodectus spiders have great potential in
      insect pest control; however, more studies are needed to further reveal their
      mechanisms of action and understand their structures and properties before any
      practical application, for example, the insecticidal toxin-containing fusion
      proteins with oral activity. Here, we review current knowledge of the molecular
      basis and mechanism of action underlying the insecticidal activity of venoms and
      toxins from Latrodectus spiders, and examine their potential application in
      insect pest control. (c) 2018 Society of Chemical Industry.

PMID- 30204934
TI  - Parkin: one of the guardians of mitochondrial function and skeletal muscle
      contractility.

PMID- 30204935
TI  - c.125_126insT mutation in ABO*B.01 allele responsible for Bel phenotype.

PMID- 30204936
TI  - Fibronectin-1 modulated by the long noncoding RNA OIP5-AS1/miR-200b-3p axis
      contributes to doxorubicin resistance of osteosarcoma cells.
AB  - Chemoresistance has been an obstacle in the further improvement of 5-year
      survival rates of osteosarcoma (OS) patients, but the underlying mechanism of
      chemo-resistance remains unclear. A comprehensive analysis of mRNAs and noncoding
      RNAs related to OS chemo-resistance could help solve this problem. In the current
      study, we first identified that fibronectin-1 (FN1), screened by microarray
      analysis in three paired chemo-resistant and chemo-sensitive OS cell lines, was
      significantly upregulated in the chemo-resistant OS cell lines and tissues and
      was related to unfavourable prognosis. Further functional assays revealed that
      FN1 inhibition greatly increased the sensitivity of OS cells to doxorubicin in
      vitro and in vivo, whereas FN1 overexpression had the opposite effect. Moreover,
      mechanistic investigation demonstrated, by a series of assays that included
      luciferase reporter gene, RNA immunoprecipitation, RNA pull-down and rescue
      assays, that FN1 expression was regulated by the oncogenic long noncoding RNA
      (lncRNA) OIP5-AS1 through sponging miR-200b-3p. Thus, these results indicated the
      role and potential application of the lncRNA OIP5-AS1/miR-200b-3p/FN1 regulatory
      pathway as a promising target in treatment of OS chemo-resistance.

PMID- 30204937
TI  - Cardiovascular Complications After Liver Transplant: A Shifting Clinical
      Presentation.

PMID- 30204938
TI  - The True Fate of Pyridinium in the Reportedly Pyridinium-Catalyzed Carbon Dioxide
      Electroreduction on Platinum.
AB  - Protonated pyridine (PyH+ ) has been reported to act as a peculiar and promising
      catalyst for the direct electroreduction of CO2 to methanol and/or formate.
      Because of recent strong incentives to turn CO2 into valuable products, this
      claim triggered great interest, prompting many experiments and DFT simulations.
      However, when performing the electrolysis in near-neutral pH electrolyte, the
      local pH around the platinum electrode can easily increase, leading to Py and
      HCO3 - being the predominant species next to the Pt electrode instead of PyH+ and
      CO2 . Using a carefully designed electrolysis setup which overcomes the local pH
      shift issue, we demonstrate that protonated pyridine undergoes a complete
      hydrogenation into piperidine upon mild reductive conditions (near 0 V vs. RHE).
      The reduction of the PyH+ ring occurs with and without the presence of CO2 in the
      electrolyte, and no sign of CO2 electroreduction products was observed, strongly
      questioning that PyH+ acts as a catalyst for CO2 electroreduction.

PMID- 30204939
TI  - Oral Glucose Tolerance is Associated with Neuroelectric Indices of Attention
      Among Adults with Overweight and Obesity.
AB  - OBJECTIVE: This study aimed to elucidate the relationship between glucose levels
      and insulin resistance and sensitivity obtained from oral glucose tolerance tests
      and neurophysiological indices of attention among adults with overweight and
      obesity. METHODS: Forty adults with overweight or obesity (BMI >= 25 kg/m2 )
      underwent dual-energy x-ray absorptiometry to assess visceral adipose tissue.
      Repeated venous blood samples were collected during an oral glucose tolerance
      test to measure insulin resistance (homeostatic model assessment of insulin
      resistance) and indices of insulin sensitivity (Matsuda index and Stumvoll
      metabolic clearance rate). Attention was assessed using event-related brain
      potentials recorded during a visual oddball task. Amplitude and latency of the P3
      wave form in a central-parietal region of interest were used to index attentional
      resource allocation and information processing speed. RESULTS: Following
      adjustment for visceral adipose tissue, reduced values of Matsuda index and
      Stumvoll metabolic clearance rate (indicating poor insulin sensitivity) were
      correlated with longer peak latency, whereas insulin area under the curve was
      positively related to peak latency, indicating slower information processing.
      Individuals with decreased insulin sensitivity (Matsuda index < 4.3) had
      significantly longer P3 latencies compared with individuals with normal insulin
      sensitivity. CONCLUSIONS: Higher fasting glucose, but not homeostatic model
      assessment of insulin resistance, and reduced indices of glucose sensivity are
      associated with decrements in attention characterized by slower reaction time and
      slower information processing speed among adults with overweight and obesity.

PMID- 30204940
TI  - Lifestyle Intervention Decreases Urine Trimethylamine N-Oxide Levels in
      Prepubertal Children with Obesity.
AB  - OBJECTIVE: Early lifestyle interventions in children with obesity decrease risk
      of obesity and metabolic disorders during adulthood. This study aimed to identify
      metabolic signatures associated with lifestyle intervention in urine samples from
      prepubertal children with obesity. METHODS: Thirty-four prepubertal children with
      obesity were studied before and after a 6-month lifestyle intervention program,
      and anthropometric, metabolic, and nutritional variables were collected. A
      nuclear magnetic resonance approach was applied to obtain the metabolomic profile
      from urine samples. Partial least squares-discriminant analysis (PLS-DA) was used
      to achieve group classification and variable importance on projection (VIP) for
      biomarker selection. RESULTS: The intervention reduced caloric intake by 10% (P <
      0.05) and BMI standard deviation score by 0.47 SD (P < 0.001). PLS-DA identified
      trimethylamine N-oxide (TMAO, VIP = 2.21) as the metabolite with the highest
      discrimination properties between groups. Urine TMAO levels were reduced after
      the intervention (P < 0.05). TMAO is a biomarker of cardiovascular disease risk
      and is a product of gut microbiota-dependent metabolism of certain dietary
      compounds, including choline. Notably, changes in TMAO levels after the
      intervention did not correlate to differences in choline intake but were
      inversely associated with fiber intake (P < 0.05). CONCLUSIONS: These results
      indicate that lifestyle intervention decreases TMAO levels in children with
      obesity.

PMID- 30204941
TI  - Stimuli-Responsive Tannin-FeIII Hybrid Microcapsules Demonstrated by the Active
      Release of an Anti-Tuberculosis Agent.
AB  - A simple and facile strategy for the creation of ferric tannin microcapsules
      around a liquid, non-sacrificial core is described. The assembly of the capsules
      occurs rapidly once ferric tannin complexes are subjected to ultrasonic
      treatment. The driving forces for the rapid capsule assembly reside in the
      strategy of adding ferric ions into the initial emulsion, which promotes shell
      formation and stability through well-known complexation effects. This is the
      first time that microcapsule assemblies of monomeric tannins like
      epigallocatechin-3-O-gallate has been demonstrated, which are reportedly unable
      to form dispersing microcapsules in the absence of a templating metal. The
      efficacy of the approach is demonstrated by the complete release of a hydrophobic
      molecule that is active against M. tuberculosis by using Acacia tannin capsules.
      The release kinetics of the active molecule were of zeroth order over a 12 h time
      frame.

PMID- 30204943
TI  - Longstanding history of verrucous tumors on both lower legs.

PMID- 30204942
TI  - Age at Introduction of Solid Food and Obesity Throughout the Life Course.
AB  - OBJECTIVE: This study aimed to examine the association between age at solid food
      (SF) introduction and obesity throughout the life course. METHODS: Among 31,816
      mother- nurse daughter dyads in the Nurses' Mothers' Cohort Study and the Nurses'
      Health Study II, information was collected on age at SF introduction, body
      somatotype at ages 5 and 10, and Body Mass Index at age 18 and in adulthood. Odds
      ratios (ORs) and 95% confidence intervals (95% CIs) for obesity throughout life
      were estimated using logistic regression models with adjustment for parental and
      nurse daughter covariates. RESULTS: Nurse daughters introduced to SF at >= 9
      months versus 6 to 9 months had marginally higher age-adjusted (OR: 1.21; 95% CI:
      1.01, 1.47) and covariate-adjusted (OR: 1.22; 95% CI: 1.01, 1.47) odds of obesity
      at age 5. Age at SF introduction was not related to obesity at ages 10 and 18 or
      in adulthood. CONCLUSIONS: Late age at SF introduction was marginally associated
      with obesity at age 5, but this association did not persist throughout the life
      course.

PMID- 30204944
TI  - Response to Alleva and Tylka and Flint et al.

PMID- 30204948
TI  - Neutrophil-red blood cell rosetting in a patient with autoimmune hemolytic
      anemia.

PMID- 30204946
TI  - Cardiac stress biomarkers after red blood cell transfusion in patients at risk
      for transfusion-associated circulatory overload: a prospective observational
      study.
AB  - BACKGROUND: Transfusion-associated circulatory overload (TACO) is a leading cause
      of serious reactions. In regard to TACO, little is known regarding biomarkers as
      a predictor, their most informative timing, or thresholds of significance or
      differentiation from other reactions. STUDY DESIGN AND METHODS: In this study of
      inpatients at risk for TACO (age >= 50 years) receiving 1 red blood cell unit,
      cardiac biomarkers, brain natriuretic peptide (BNP), N-terminal pro-BNP (NT
      proBNP), and high-sensitivity troponin were measured at baseline, 6 to 12 hours
      (except troponin) posttransfusion, and 18 to 24 hours posttransfusion. Primary
      outcome was a critical increase in biomarkers (>1.5-fold increase and
      supranormal) at 18 to 24 hours. RESULTS: Fifty-one patients were analyzed; 29%
      had cardiovascular disease, 73% had one or more cardiac risk factors, and 50%
      took cardiac or antihypertensive therapies. Although eight (16%) developed an
      increase in systolic pressure of at least 30 mmHg and four (8%) reported dyspnea
      and/or cough, none had TACO. At baseline, BNP level was more than 100 ng/L in 59%
      and NT-proBNP was more than 300 pg/mL in 83%. A total of 25% had a BNP critical
      increase, 33% had a NT-proBNP critical increase, and 2% had a troponin critical
      increase at 18 to 24 hours. Overall, 38% had at least one biomarker critical
      increase and NT-proBNP/BNP concordance was 84%. An increase in the NT-proBNP
      (>1.5-fold increase and >300 pg/mL) at 18 to 24 hours was the commonest biomarker
      change. CONCLUSIONS: An increase of the NT-proBNP at 18 to 24 hours may be the
      preferred surrogate marker for identifying a patient experiencing physiologic
      difficulty in handling the volume challenge. Larger studies are needed to clarify
      the risk of TACO for a given pretransfusion biomarker profile and the correlation
      between TACO and increase in biomarkers after transfusion.

PMID- 30204947
TI  - Impact of collection programs for the generation of monocyte apheresis products
      on product quality and composition as starting material for the generation of
      cellular therapeutics.
AB  - BACKGROUND: With the discontinuation of the last generation of apheresis
      machines, new options for monocyte apheresis became available. As apheresis
      products play a crucial role in the generation of new cellular therapeutics
      (e.g., generation of dendritic cells [DCs] or precursor for T-cell experiments)
      we sought to compare two different collection programs for potential benefits or
      disadvantages due to different composition of the cellular products. STUDY DESIGN
      AND METHODS: Composition of discontinuously and continuously collected monocyte
      products from the same 13 donors was analyzed. For further evaluation as starting
      material for manufacturing of cellular therapeutics typically used steps such as
      Ficoll Isopaque, cryoconservation and monocyte isolation, with subsequent
      generation of mature DCs (mDCs) and assessment of T-cell function, were performed
      on seven of these apheresis pairs. RESULTS: Yield of total cells, monocytes, and
      mDCs was equal with both methods. T-cell composition did not differ significantly
      in content of CD3+, CD4+, and CD8+ cells. Differentiation status and cytokine
      production of CD8+ T cells upon stimulation with cytomegalovirus pp65 antigen was
      not significantly different. CONCLUSION: Both methods seem comparably suited for
      the generation of cellular products. If the intended use is "fresh" (without
      cryoconservation), continuously harvested cells show better cell numbers, while
      discontinuously harvested cells show better recovery after cryoconservation.

PMID- 30204949
TI  - Donor screening for hepatitis B: hepatitis B surface antigen-a belt, suspenders,
      and another belt?

PMID- 30204945
TI  - BRCA1 and BRCA2 5' noncoding region variants identified in breast cancer patients
      alter promoter activity and protein binding.
AB  - The widespread use of next generation sequencing for clinical testing is
      detecting an escalating number of variants in noncoding regions of the genome.
      The clinical significance of the majority of these variants is currently unknown,
      which presents a significant clinical challenge. We have screened over 6,000
      early-onset and/or familial breast cancer (BC) cases collected by the ENIGMA
      consortium for sequence variants in the 5' noncoding regions of BC susceptibility
      genes BRCA1 and BRCA2, and identified 141 rare variants with global minor allele
      frequency < 0.01, 76 of which have not been reported previously. Bioinformatic
      analysis identified a set of 21 variants most likely to impact transcriptional
      regulation, and luciferase reporter assays detected altered promoter activity for
      four of these variants. Electrophoretic mobility shift assays demonstrated that
      three of these altered the binding of proteins to the respective BRCA1 or BRCA2
      promoter regions, including NFYA binding to BRCA1:c.-287C>T and PAX5 binding to
      BRCA2:c.-296C>T. Clinical classification of variants affecting promoter activity,
      using existing prediction models, found no evidence to suggest that these
      variants confer a high risk of disease. Further studies are required to determine
      if such variation may be associated with a moderate or low risk of BC.

PMID- 30204950
TI  - Pathogen-inactivated blood products for pediatric patients: blood safety, patient
      safety, or both?

PMID- 30204952
TI  - Safety and efficacy of cryopreserved platelets in bleeding thrombocytopenic
      patients.

PMID- 30204951
TI  - Comparison of automated and manual methods for washing red blood cells.
AB  - BACKGROUND: We sought to compare the quality of washed red blood cells (RBCs)
      produced using the ACP215 device or manual methods with different combinations of
      wash and storage solutions. Our aim was to establish manual methods of washing
      that would permit a shelf life of more than 24 hours. STUDY DESIGN AND METHODS:
      Fourteen-day-old RBCs were pooled, split, and washed in one of five ways: 1)
      using the ACP215 and stored in SAGM, 2) manually washed and stored in saline, 3)
      manually washed in saline and stored in SAGM, 4) manually washed in saline
      glucose and stored in SAGM, and 5) manually washed and stored in SAGM. Additional
      units were pooled and split, washed manually or using the ACP215, and irradiated
      on Day 14. Units were sampled to 14 days after washing and storage at 4 +/- 2
      degrees C. RESULTS: All washed RBCs met specification for volume (200-320 mL) and
      hemoglobin (Hb) content (>40 g/unit). Removal of plasma proteins was better using
      manual methods: residual immunoglobulin A in saline-glucose-washed cells 0.033
      (0.007-0.058) mg/dL manual versus 0.064 (0.026-0.104) mg/dL ACP215 (median,
      range). Hb loss was lower in manually washed units (mean, <= 2.0g/unit) than in
      ACP215-washed units (mean, 6.1 g/unit). Disregarding saline-washed and stored
      cells, hemolysis in all nonirradiated units was less than 0.8% 14 days after
      washing. As expected, the use of SAGM to store manually washed units improved
      adenosine triphosphate, glucose, lactate, and pH versus storage in saline.
      CONCLUSION: The data suggest that the shelf life of manually washed RBCs could be
      extended to 14 days if stored in SAGM instead of saline.

PMID- 30204954
TI  - Cryopreserved platelets: are we there yet?

PMID- 30204953
TI  - Safety and efficacy of cryopreserved platelets in bleeding patients with
      thrombocytopenia.
AB  - BACKGROUND: The short dating period of room temperature-stored platelets (PLTs; 5
      7 days) limits their availability at far-forward combat facilities and at remote
      civilian sites in the United States. PLT cryopreservation in 6% DMSO and storage
      for up to 2 years may improve timely availability for bleeding patients. STUDY
      DESIGN AND METHODS: A dose escalation trial of DMSO-cryopreserved PLTs (CPPs)
      compared to standard liquid-stored PLTs (LSPs) was performed in bleeding patients
      with thrombocytopenia. Within each of four cohorts, six patients received
      escalating doses of CPP (0.5 unit, 1 unit, and sequential transfusions of 2 and 3
      units) and one received a LSP transfusion. Patients were monitored for adverse
      events (AEs), coagulation markers, PLT responses, and hemostatic efficacy.
      RESULTS: Patients with a World Health Organization bleeding score of 2 or more
      received from 0.5 to 3 units of CPP (n = 24) or 1 unit of LSP (n = 4). There were
      no related thrombotic or other serious AEs experienced. Mild transfusion-related
      AEs of chills and fever (n = 1), transient increased respiratory rate (n = 1),
      DMSO-related skin odor (n = 2), and headache (n = 1) were observed after CPP
      transfusion. Among CPP recipients 14 of 24 (58%) had improved bleeding scores,
      including three of seven (43%) patients who had intracerebral bleeding. CPP
      posttransfusion PLT increments were significantly less than those of LSPs;
      however, days to next transfusion were the same. After transfusion, the CPP
      recipients had improvements in some variables of thrombin generation tests and
      thromboelastography. CONCLUSION: Cryopreserved PLT transfusions appear to be safe
      and effective when given to bleeding patients with thrombocytopenia.

PMID- 30204955
TI  - Current practices for viability testing of cryopreserved cord blood products: an
      international survey by the cellular therapy team of the Biomedical Excellence
      for Safer Transfusion (BEST) Collaborative.
AB  - BACKGROUND: Viability testing is a common practice in laboratories. The goal of
      this study was to ascertain current laboratory practices internationally for
      performing viability testing for cryopreserved cord blood (CB) products and glean
      information about how to standardize the method to improve interlaboratory
      reproducibility. STUDY DESIGN AND METHODS: A survey to evaluate current
      laboratory practices for viability testing was designed and distributed
      internationally. The question topics included sampling and testing methods,
      responses to unexpected results, and the rating of the reliability of the CB
      quality tests, together with expectations for standardization. RESULTS: There
      were 32 respondents to the survey, of whom 28 responded to the more detailed
      questionnaire about viability methods. Overall, responses indicated that various
      stains were used among the laboratories, and when multiple sites used the same
      viability stain the methods differed. The majority of the respondents were in
      favor of standardizing the viability testing methods. A wide variety of
      preferences were communicated about how to standardize the method, but a majority
      did advocate the use of 7-aminoactinomycin D (7-AAD) with flow cytometry.
      CONCLUSIONS: The survey results revealed a variety of tests and inconsistent
      interlaboratory practices for performing the viability assay. Flow cytometry with
      a 7-AAD dye was suggested as a first step toward standardization.

PMID- 30204957
TI  - Muttarak's Study Design Cannot Support the Link Between the Body-Positive
      Movement and Overweight or Obesity.

PMID- 30204956
TI  - Bioinspired Architectures and Heteroatom Doping To Construct Metal-Oxide-Based
      Anode for High-Performance Lithium-Ion Batteries.
AB  - The pursuit of increased energy density and longer lifespan lithium-ion batteries
      (LIBs) is urgently needed to satisfy a dramatically increased demand in the
      energy market. Currently, metal-oxide-based anodes are being intensively studied
      due to their higher capacities over current graphite anodes. This work introduces
      a sustainable strategy to construct a metal-oxide-based anode with high capacity
      and an extremely long lifecycle, in which the features of bioinspired
      architectures and heteroatom doping can contribute greatly to increased
      performances. In detail, 1D tubelike metal oxide (e.g., MnO) coated on an N-doped
      carbon framework (i.e. MnO/N-C) has been designed by using the naturally abundant
      and renewable Metaplexis japonica fibers (MJFs) as the biotemplate and heteroatom
      source. Benefiting from the uniqueness of structure and compositions, as-prepared
      MnO/N-C demonstrates extremely high rate capacities of 951, 777, 497, and 435 mAh
      g-1 at the rates of 0.5, 2, 4, and 5 Ag-1 , respectively, with a good stability
      of more than 1000 cycles. It was found that the electrochemical performances are
      superior to most previous MnO-based anodes, in which the faster kinetics of
      conversion due to the advantage of the ion/electron transportation and
      morphological evolution has been verified. It is hoped that the concept of
      bioinspired architectures with heteroatom doping can be applied in wider
      applications for increased capability.

PMID- 30204958
TI  - THE RELATIONSHIP BETWEEN CONGENITAL HEART DEFECTS AND e-NOS GENE IN DOWN
      SYNDROME.
AB  - The aim of the study was to compare the effects of three eNOS gene polymorphisms
      associated with congenital heart defects, between Down syndrome patients with and
      without cardiac anomalies. Transthoracic echocardiographic examinations and eNOS
      single-nucleotide polymorphisms were investigated on seventy-five patients,
      prospectively. The frequencies of mutant alleles in the eNOS promoter (the 
      786T/C polymorphism) and exon 7 mutant alleles (the 894G--->T polymorphism) were
      significantly higher in Down syndrome patients with and without cardiac
      anomalies. The frequency of the intron GIOT polymorphism did not significantly
      differ between patients with and without cardiac anomalies. We found a
      significant relationship between eNOS gene polymorphisms and the congenital heart
      defects in patients with Down syndrome. Screening for the presence or absence of
      eNOS polymorphisms may be useful to obtain preliminary data on the risk of
      congenital heart defects in patients with Down syndrome.

PMID- 30204959
TI  - PARTIAL TRISOMY 5p12-q 11.2 RESULTING FROM A MARKER CHROMOSOME: A NEW CASE REPORT
      WITH ATTENTION DEFICIT HYPERACTIVITY DISORDER.
AB  - Partial trisomy of chromosome 5 was first described by Lejeune et al. in 1964 on
      the short arm (12). The vast majority of the partial trisomy 5 cases include 5p
      duplications; however we reported a small supernumerary marker chromosome.
      General symptoms include developmental delay, mental retardation, seizures,
      respiratory difficulties, congenital heart defects, abdominal muscle hypoplasia
      and dysmorphic features such as macrocephaly, enlarged anterior fontanelle,
      dolichocephaly, upslanting palpebral fissures, epicanthal folds, hypertelorism,
      abnormal ears, midface hypoplasia, short nose, broad nasal bridge and
      microretrognathia. Arachnodactyly and club foot may be seen as cytoskeletal
      abnormalities and, hypotonia may be determined in neurological exam. Here we
      reported a case with developmental delay, attention deficit hyperactivity
      disorder, mild mental retardation and dysmorphic features, caused by a new small
      supernumerary marker chromosome, generating partial trisomy 5pI 2-q 11.2. To our
      knowledge, this small supernumerary marker chromosome has not been reported
      before. Severe type of partial trisomy 5 includes seizures, congenital heart
      defects, hypotonia and failure to thrive. Previously reported partial trisomy 5
      cases, who showed severe phenotype, had usually duplicated 5p13 region.
      Therefore, patients, who do not have duplicated 5p13, showed mild phenotype.
      Also, duplication of the long arm of chromosome 5, may contribute to the milder
      phenotype and the longer survival in partial trisomy 5 patients. Attention
      deficit hyperactivity disorder, which we described in the present case, may be a
      result of partial trisomy 5, because it includes ADHD4 gene. This case may help
      better understanding the karyotype/phenotype correlation related to partial
      trisomy 5.

PMID- 30204961
TI  - PHENOTYPIC CONSEQUENCES AND THE MALIGNANCY RISK IN FAMILIAL NOONAN SYNDROME DUE
      TO A RARE P.S427G RAF1 MUTATION.
AB  - Mutations leading to dysregulation of the Ras/MAPK signal transduction cascade
      are a common cause of Noonan syndrome (NS) and play a key role in the
      pathogenesis of many human malignancies. To date, about 24 various RAF1 germline
      mutations were identified in NS. The incidence of malignancies in NS patients
      with RAF1 mutations has not been reported so far. However, in a few cases somatic
      RAF1 mutations were observed in cancer, including two described in therapy
      related acute myeloid leukaemia (t-AML). We present a case of an adult female
      patient with Noonan syndrome and her affected mother with a rare RAF] germline
      mutation c.1279A>G (p.S427G), located within the highly conserved domain (CR3) of
      serine/threonine kinase C-RAF. Interestingly, this mutation has been reported for
      the first time in a patient with t-AML as a somatic change and so far has been
      identified in only one individual with NS phenotype and his mother. Our report
      presents the second familial case of Noonan syndrome due to a germline p.S427G
      substitution in RAF] with no occurrence of a malignant tumor. It may suggest that
      carrying a germline mutation in the RAF1 oncogene is not associated with an
      increased risk of tumor development. Since RAF1 mutations have been observed as a
      somatic event in many types of cancer, this report might be of importance for the
      genetic counselling and management of patients both with germline and somatic
      alterations in this gene.

PMID- 30204960
TI  - ROBERTS SYNDROME: CLINICAL AND CYTOGENETIC STUDIES IN 8 EGYPTIAN PATIENTS AND
      MOLECULAR STUDIES IN 4 PATIENTS WITH GENOTYPE/PHENOTYPE CORRELATION.
AB  - The Roberts syndrome (RBS) is a rare autosomal recessive disorder caused by
      mutation in ESCO2 gene. Among over 150 reported international cases, 16 cases are
      Egyptian including the presently reported patients. The current study reports 8
      new Egyptian patients from 7 unrelated consanguineous families investigating
      clinical phenotype as well as cytogenetic changes in all cases and mutational
      spectrum in 4 cases. Clinical, orodental, cytogenetic and molecular studies were
      done to investigate genotype/phenotype correlation. Evaluation of the studied 8
      patients showed that they all exhibited the main limb and craniofacial features
      of Roberts syndrome. Cytogenetic studies including centromeric separation and
      puffing by Giemsa and DAPI stains and for the first time in Egypt analysis for
      premature centromeric division by FISH showed consistent centromeric separation
      in all studied cases. Molecular studies of 4 available patients showed that they
      all have ESCO2 gene mutation. We conclude that RBS has a well-defined clinical
      spectrum. The cytogenetic changes are due to sister chromatid cohesion defects
      which lead to mitotic dysfunction. We confirmed previous results of lack of
      genotype/phenotype correlation. We also confirmed that the severity of limb
      malformation correlates with craniofacial manifestations. We recommend detailed
      evaluation of orodental changes for further definition of the phenotype and for
      proper patient management. We emphasize the need for further studies for the
      frequency of premature centromeric separation by FISH as a possible indicator of
      phenotypic severity.

PMID- 30204962
TI  - ASSOCIATED ANOMALIES IN CASES WITH LIMB REDUCTION DEFICIENCIES.
AB  - Infants with limb reduction deficiencies (LRD) often have other associated
      congenital anomalies. The purpose of this investigation was to assess the
      prevalence and the types of associated anomalies in a defined population. The
      associated anomalies in infants with LRD were collected in all livebirths,
      stillbirths and terminations of pregnancy during 29 years in 387,067 consecutive
      births in the area covered by our population-based registry of congenital
      malformations. Of the 317 infants bom with LRD during this period, representing a
      prevalence of 8.2 per 10,000, 59.9% had associated anomalies. There were 27
      (8.5%) cases with chromosomal abnormalities including 17 trisomies 18, and 73
      (23.0%) nonchromosomal recognized dysmorphic conditions including 19 VA(C)TER(L)
      association and 15 Poland syndrome. However, numerous other recognized dysmorphic
      conditions were registered. Ninety (28.4%) of the cases had multiple congenital
      anomalies (MCA). Anomalies in the musculoskeletal, the cardiac, the urogenital,
      and the central nervous system were the most common other anomalies. This study
      included special strengths: each affected child was examined by a geneticist, all
      elective terminations were ascertained, and the surveillance for anomalies was
      continued until 2 years of age. Therefore the overall prevalence of associated
      anomalies, which was more than one in two infants, emphasizes the need for a
      thorough investigation of infants with LRD. A routine screening for other
      anomalies especially in the musculoskeletal system, the cardiovascular system,
      the urogenital system, the central nervous system, and the digestive system may
      be considered in infants and in fetuses with LRD.

PMID- 30204963
TI  - ICHTHYOSIS LINEARIS CIRCUMFLEXA: NOT ALWAYS A PART OF NETHERTON SYNDROME.
AB  - Ichthyosis Linearis Circumfiexa (ILC) is a rarely seen autosomal recessive
      keratinization disorder and is characterized by erythematous, polycystic, plaques
      with 'double-edged' scales. Its histological features resemble psoriasis. A triad
      of ichthyosis (usually Ichthyosis Linearis Circumfiexa), trichorrhexis invaginata
      (a distinctive hair shaft disorder) and atopy is named as Netherton syndrome.
      Herein, we report a 12 year-old girl presenting with ILC not accompanied with
      typical atopy findings and hair shaft disorder.

PMID- 30204964
TI  - TWO CASES WITH DIFFERENT EPILEPSY TYPE AND DYSMORPHIC FEATURES ASSOCIATED WITH
      17q21.31 MICRODELETION SYNDROME.
AB  - The 17q21.31 microdeletion syndrome is characterized by intellectual disability,
      epilepsy, facial dysmorphism and friendly behavior. Recently, KANSLJ gene has
      been considered as a major causal gene for this phenotype. Here we report on two
      Turkish patients with different seizure types and additional dysmorphic features
      associated with 17q21.31 microdeletion syndrome. A 4 year-old female patient with
      generalized tonic-clonic seizures, mild mental retardation, dysmorphic features
      and friendly behavior and a 14 years-old female with intractable epilepsy,
      different dysmorphic features, severe mental and motor retardation and self
      mutilation were evaluated by array-based comparative genomic hybridization
      (microarray CGH). Array CGH identified 17q21.31 microdeletion that contains MAP7
      CRHR1, KANSLI, PLEKHMI genes in case I and CRHR1, PLEKHM but not KANSLJgenes in
      case 2. To the best of our knowledge this is the first report of a patient with
      the 17q21.31 microdeletion which does not encompass KANSLI gene. These data imply
      another gene or genes causing similar phenotype in this patient.

PMID- 30204965
TI  - AN UNUSUAL PRESENTATION OF JOUBERT SYNDROME AND RELATED DISORDERS IN A NEWBORN:
      PANHYPOPITUITARISM.
AB  - The Joubert syndrome is characterized by hypotonia, ataxia, facial dysmorphism,
      abnormal eye movement, irregular breathing pattern and cognitive impairment. The
      molar tooth sign is the pathognomonic midbrain-hindbrain malformation for Joubert
      syndrome. Joubert syndrome and related disorders (JSRD), are the clinically and
      genetically heterogen disorders in which the obligatory hallmark is the molar
      tooth sign (MTS). In this report, it was described the association of the molar
      tooth sign, absence of pituitary gland and corpus callosum agenesis on an infant
      with JSRD. To the best of our knowledge, this is the first case diagnosed as JSRD
      and panhypopituitarism without features of OFD VI.

PMID- 30204966
TI  - MUCOLIPIDOSIS II INFANTS PRESENTING WITH SKELETAL DEFORMITIES MIMICKING RICKETS
      AND A NEW MUTATION IN GNPTAB GENE.
AB  - Mucolipidosis II or I-cell disease is a rare lysosomal enzyme hydrolase
      trafficking due to deficient activity of the multimeric enzyme UDP
      Nacetylglucosamine-l-phosphotransferase. It is a severe inborn error of lysosomal
      storage that causes progressive multisystem deterioration and death within the
      first year of life. The diagnosis of ML II is often difficult in an infant due to
      clinical variety, phenotypic overlap and the enzyme analysis required.
      Mucolipidosis II and rickets may have similar physical, biochemical and
      radiographic findings in newborns. The diagnosis of Mucolipidosis II is often
      missed, as it may present with rickets-like picture. In this article, we describe
      two neonatal mucolipidosis II patients mimicking rickets, and we evaluated them
      by clinical, metabolic and imaging findings via literature and also emphasized
      the difficulties in diagnosis of this rare disease.

PMID- 30204968
TI  - SUBMICROSCOPIC DUPLICATION OF 8q24.3 REGION IS A POTENTIAL CANDIDATE FOR
      DISORDERS OF SEX DEVELOPMENT.
AB  - Some of the disorders of sex development (DSD), including 46, XX testicular DSD
      formerly called "XX maleness" and 46, XY DSD with partial or complete gonadal
      dysgenesis primarily affect the gonads. Genetic alterations in ten unrelated
      females with complete 46, XY gonadal dysgenesis (GD) were analyzed using an Array
      2.7 M platform with whole genome coverage. The analysis result suggested that the
      most significant region maps to chromosome 8q24.3 which were previously reported
      by another independent study with a similar patient cohort and this region being
      probable candidate related to complete 46, XY GD.

PMID- 30204967
TI  - GENETIC COUNSELLING IN FEINGOLD SYNDROME AND A NOVEL MUTATION.
AB  - Feingold syndrome (FS) is an autosomal dominant hereditary disorder characterised
      by finger and toe abnormalities, microcephaly, facial dysmorphism,
      gastrointestinal atresias such primarily as oesophageal and/or duodenal atresia
      and mild to moderate mental retardation. Approximately 60% of cases have an
      affected parent. MYCN is the only gene in which mutations are known to cause FS.
      In this report, we present a case with Feingold Syndrome having a novel mutation
      in MYCN gene and discuss genetic counselling and prenatal diagnosis due to
      pregnancy of the patient's mother.

PMID- 30204969
TI  - A NEW ISOLATED 20q INTERSTITIAL DUPLICATION CASE AND ITS CLINICAL COMPARISON WITH
      SIMILAR ISOLATED CASES.
AB  - Duplications of 20q are rare. Here we report a 15 years old boy with de novo
      duplication of 17.1 Mb at chromosome 20q. We made a comparison with the other
      isolated 20q duplication cases. There are phenotypic similarities between the
      patients who have the same affected chromosomal regions. We also showed a
      clinical follow up of the patient. There may be a relationship with Glaucoma and
      Graves disease between the chromosomal region and these diseases may occur at the
      other patients when they get older.

PMID- 30204970
TI  - COBALAMIN C DEFICIENCY WITH INFANTILE SPASM AND CUTANEOUS FINDINGS: A UNIQUE
      CASE.
AB  - Cobalamin C (CbIC) deficiency is a rare disorder of vitamin B12 metabolism which
      results from impaired conversion of both its active forms methylcobalamin and
      adenosylcobalamin. Early onset cblC typically presents in the first year of life
      with hypotonia, lethargy, seizures, microcephaly, hydrocephalus, developmental
      delay and other multisystem involvement including hematologic, ocular, renal,
      hepatic and cardiac symptoms. We report a case of a female infant with cblC
      deficiency who presented with seizures, developmental delay and hypopigmented
      cutaneous lesions. To our knowledge, the patient is the first diagnosed with cblC
      deficiency who had skin hypopigmentation.

PMID- 30204971
TI  - MATTHEW-WOOD SYNDROME: A CASE WITH DEXTROCARDIA AND STREAK GONADS.
AB  - Matthew-Wood syndrome (MWS), also termed Microphthalmia, syndrome 9 (MCOPS9, MIM
      601186), Spear syndrome, or pulmonary hypoplasia, diaphragmatic hernia,
      anophthalmia and cardiac defects syndrome (PDAC syndrome), is an autosomal
      recessive disorder characterised by ocular, respiratory and cardiac
      abnormalities. Mutations in retinoic acid 6 gene (STRA6) have been reported in
      clinically diagnosed patients with MWS. Here we presented a case with MWS, who
      has characteristic findings of the syndrome as well as dextrocardia as an
      undescribed feature, and bilateral streak gonads which was described only in one
      patient previously. Molecular analysis showed a homozygous exonic missense
      mutation in the STRA6 gene.

PMID- 30204972
TI  - THE 3rd W522X MUTATION IN EIF2AK3 GENE FROM TURKEY: A NEW PATIENT WITH WOLCOTT
      RALLISON SYNDROME.
AB  - Wolcott-Rallison Syndrome (WRS), also known as Multiple Epiphyseal Dysplasia with
      Early-onset Diabetes Mellitus is a rare autosomal recessive multisystemic
      disorder. Its characteristic clinical features are permanent neonatal or early
      infancy insulin-dependent diabetes and later onset skeletal dysplasia. Other
      frequent clinical manifestations are hepatic and renal dysfunction, mental
      retardation, cardiac abnormalities, exocrine pancreatic dysfunction, primary
      hypothyroidism and neutropenia. This report presents an 8-year-old WRS case who
      is found to have W522X mutation in EIF2AK3 gene which was only found in two other
      unrelated Turkish families. W522X mutation in EIF2AK3 gene seems to be confined
      to Turkey and may be a common mutation in WRS patients from this country. In this
      paper, we evaluate the clinical features of the patients having W522X mutation
      and we compare this group with other patients reported to date. Except the
      characteristic features as diabetes mellitus and epiphyseal dysplasia, all the
      WRS patients, including patients with W522X mutation, show extensive phenotypic
      variability that correlates poorly to genotype which suggests that there is no
      correlation between a specific mutation and the clinical manifestation.

PMID- 30204973
TI  - SEVERE HYDROCEPHALUS, KIDNEY AND SKELETAL ANOMALIES IN A FEMALE PATIENT WITH MILD
      NEUROLOGICAL ALTERATIONS.
AB  - The appearance of untreated severe hydrocephalus with long-term survival is
      infrequent; here we report a case with these characteristics, mild neurological
      alterations and kidney and skeletal anomalies. A female patient showed severe
      hydrocephalus (initially mistaken with hydranencephaly) at 4 years old and left
      kidney ectopia (initially mistaken with renal agenesis); however, she was derived
      to the neurology service until she was 12 years old, when she began to present
      migraine and seizures. At 13 years old the patient was diagnosed with arrested
      hydrocephalus secondary to aqueduct stenosis, and the seizures worsen thereafter
      from atonic seizures to complex partial seizures (at 14 years old), presenting
      generalized seizures at 15 years old. At 17 years old, the seizures were more
      frequent despite the anticonvulsant treatment and also presented automations, she
      was also diagnosed with genu recurvatinn and scoliosis. The seizures finally
      diminished and partially controlled at 19 years old. Despite a cerebral mantle <
      2.0 cm at the computer tomography, the patient always presented a satisfactory
      intellectual development. In this case, the relatively good and long evolution of
      the severe hydrocephalus is probably related with the late-onset of the disease
      that permitted a better development of the brain; however, the worsening of the
      seizures after the hydrocephalus arrested, suggests that arrest is not
      necessarily associated with a compensation and better evolution of the disease,
      at least at the beginning of the process. The presence of kidney ectopia and
      skeletal alterations did not associate with a known genetic disease, however a
      possible inheritance mechanism is not discarded.

PMID- 30204974
TI  - A VERY RARE CAUSE OF APNEA IN THE NEONATAL PERIOD: JOUBERT SYNDROME.

PMID- 30204975
TI  - AN INTERCHANGE TRISOMY RESULTED IN DOWN SYNDROME.

PMID- 30204976
TI  - OCULO-DENTO-DIGITAL DYSPLASIA IN A TUNISIAN FAMILY WITH A NOVEL GJA1 MUTATION.

PMID- 30204978
TI  - Where to be born or how to be born.

PMID- 30204979
TI  - A vital balance.

PMID- 30204977
TI  - DOUBLE TRISOMY MOSAICISM 48,XXX,+8/46,XX IN A FEMALE: THE FIRST REPORTED CASE.

PMID- 30204980
TI  - Prevalence of deaf people who have a professional Argentine Sign Language
      interpreter during their children's medical consultations.
AB  - INTRODUCTION: In Argentina, hearing disability accounts for 18% of disabilities.
      Argentine Sign Language (ASL) is the communication system of choice used by deaf
      people (DP). An incorrect communication with physicians hampers the adequate
      provision of health care. DP require a professional ASL interpreter (PASLI) in
      the context of health care provided to their children. National Act no. 26378
      stipulates the provision of a PASLI to facilitate access to public facilities.
      However, most DP neither have an interpreter nor know this right. OBJECTIVES: To
      describe the prevalence of DP who have a PASLI present during their children's
      medical consultations and who know their right to access one at no charge.
      MATERIAL AND METHOD: Approved and registered, descriptive, cross-sectional study
      with a structured, self-administered survey. Participants: DP who knew ASL and
      had children aged 1 month to 18 years old. Outcome variables: to have a PASLI and
      to know the right to have one. Estimated sample size: 220. Convenience sampling
      selected from the Autonomous City of Buenos Aires and the province of Chaco. The
      prevalence and 95% confidence interval (95% CI) were estimated. RESULTS: Two
      hundred and twenty-two surveys were analyzed. Age: 34.9 +/- 10.1 years old. Among
      all participants, 15.3% (95% CI: 11.1-20.6) sometimes had a PASLI during their
      children's medical consultations. Also, 48.6% (95% CI: 42.155.1) knew their right
      to have one. CONCLUSION: The prevalence of DP who had a PASLI present during
      their children's medical consultations was low. Less than a half knew their right
      to have one.

PMID- 30204981
TI  - Postoperative characteristics of combined pharyngoplasty and tonsillectomy versus
      tonsillectomy in children with obstructive sleep apnea syndrome.
AB  - PURPOSE: The study aims to identify the postoperative advantages of tonsillectomy
      in conjunction with pharyngoplasty and tonsillectomy alone in children with
      obstructive sleep apneas. METHODS: In a prospective observational study, patients
      who met the study criteria were randomly divided into two groups: tonsillectomy
      and pharyngoplasty group, and tonsillectomy alone group. In both groups,
      adenoidectomy was also performed in patients with adenoid hypertrophy.
      Differences in their healing processes in the pharyngeal wound and their
      hemorrhage proportions were compared. Furthermore, postoperative velopharyngeal
      function was also assessed. RESULTS: Pharyngoplasty together with tonsillectomy
      was performed in 328 children with obstructive sleep apnea from tonsillar
      hypertrophy, and tonsillectomy was performed in 275 children. These cohorts did
      not reveal any significant demographic differences between groups. Furthermore,
      blood loss was found to be significantly decreased in the tonsillectomy and
      pharyngoplasty group (P <0.01), and the healing process was markedly shorter.
      Postoperative velopharyngeal function was not affected. CONCLUSIONS:
      Tonsillectomy in conjunction with pharyngoplasty reduced the duration of the
      healing process and blood loss, compared with tonsillectomy alone; however,
      postoperative complications did not increase. We consider pharyngoplasty in
      conjunction with tonsillectomy has great potential in the treatment of children
      with obstructive sleep apnea.

PMID- 30204982
TI  - Prevalence of low birth weight in a scenario of economic depression in Argentina.
AB  - INTRODUCTION: Low birth weight (LBW) is considered a general indicator of health
      because it is related to complications in the life of a newborn infant and is one
      of the leading causes of infant mortality. It is a multifactorial indicator, and
      its determinants include socioeconomic factors. OBJECTIVE: To assess the impact
      of economic inequality on the prevalence of LBW by quantifying its differential
      effect by maternal age, level of maternal education, and level of care.
      POPULATION AND METHODS: Epidemiological, cross-sectional study that analyzed all
      births occurred in Argentina between 2001 and 2013 based on data provided by the
      National Registry of births, corresponding to the Health Statistics and
      Information Department. The temporal variation in the prevalence of LBW newborn
      infants (< 2500 grams) and its relation to demographic and socioeconomic
      indicators were studied. Its association was assessed using logistic regression
      models. RESULTS: A total of 9 001 960births were included. The prevalence of LBW
      newborn infants during the 2001 economic crisis increased -6% in 2002 and 7% in
      2003- The impact was heterogeneous and higher on public hospitals (|-1;PR|-3; =
      1.03) and adolescent mothers (PR=1.07), but no impact was observed on a low level
      of maternal education (PR= 0.99). CONCLUSIONS: The impact of socioeconomic
      inequality on the prevalence of LBW was significant and heterogeneous, especially
      on public hospitals and mothers at the extremes of maternal age.

PMID- 30204983
TI  - Prevalence of masked hypertension among children with risk factors for arterial
      hypertension.
AB  - INTRODUCTION: Masked hypertension (MH) in children is defined as normal office
      blood pressure values and high values outside the clinical setting. The 24-hour
      ambulatory blood pressure monitoring (ABPM) is helpful for diagnosis. There is
      little information on MH prevalence in our population. OBJECTIVE: To estimate the
      prevalence of MH in children with risk factors for arterial hypertension.
      MATERIAL AND METHOD: Prospective, observational, cross-sectional study. Patients
      seen at Hospital General de Ninos "P. de Elizalde" between July 1st, 2015 and
      December 1st, 2016, aged 5-11 years, with normal blood pressure and at least one
      risk factor for arterial hypertension were included in consecutive order. A 24
      hour ABPM was done (SpaceLabs 90207/90217). Estimated sample: 110 patients. All
      relevant authorizations were obtained. RESULTS: One hundred and ten patients aged
      8.7 +/- 1.8 years were included; 60 were girls. ABPM duration: 23.18 +/- 1.8
      hours. Twenty-three patients had neonatal history; all had at least one factor
      corresponding to personal history (the most common ones were increased salt
      intake and obesity); 101 had at least one factor corresponding to family history.
      ABPM helped to identify 10 patients with MH (9.1%; 95% confidence interval |
      1;CI|-3;: 5.1-15.9); 7 had isolated nocturnal hypertension (6.4%; 95% CI: 3.1
      23.5) and 28 had prehypertension (25.4%; 95% CI: 18.234.3). Among the 10 patients
      with MH, 7 were boys, 9 were obese and had at least one factor corresponding to
      family history. CONCLUSION: The prevalence of MH in children with risk factors
      for arterial hypertension was close to 10%.

PMID- 30204984
TI  - Post-extubation non-invasive ventilation in the pediatric intensive care unit: a
      multicenter study.
AB  - INTRODUCTION: Extubation failure is a complication that increases morbidity and
      mortality. Noninvasive ventilation (NIV) has demonstrated to be effective as
      ventilatory support therapy. OBJECTIVE: To determine the rate of postextubation
      NIV success and the factors associated with procedural failure or success.
      POPULATION AND METHODS: Design: observational, retrospective, analytical, and
      multicenter study. All patients who required post-extubation NIV during 2014 and
      2015 were included. Rescue NIV was defined as the implementation of NIV for acute
      respiratory failure; elective NIV was described as its implementation for
      prophylaxis. NIV failure was defined as the need for orotracheal intubation
      within the first 48 hours. The characteristics of failure and success and the
      types of NIV were compared, and the equipment used was assessed. RESULTS: Rescue
      NIV was required in 112 children; elective NIV, in 143. The rates of success were
      68.8% and 72.7%, respectively. Mortality was higher among patients in whom rescue
      NIV failed compared to those with successful NIV. A longer length of stay and
      more days of invasive mechanical ventilation prior to extubation were observed in
      the elective NIV group. The most common diagnosis was acute lower respiratory
      tract infection in previously healthy children. CONCLUSIONS: The use of post
      extubation NIV may be a useful tool to prevent reintubation with invasive
      mechanical ventilation. Immunocompromised patients and those with neurological
      history had a higher rate of failure. Patients with failure tolerated less hours
      of NIV and had a longer length of stay in the pediatric intensive care unit.

PMID- 30204985
TI  - Prevalence of high blood pressure among schoolchildren from Cordoba, Argentina,
      and its relation to socioeconomic status.
AB  - INTRODUCTION: Prior studies conducted in Argentina found variable prevalence
      rates of high blood pressure (HBP) among children using different measurement
      methods. The objective of this study was to know the prevalence of HBP among
      schoolchildren from the city of Cordoba and its relation to sex, nutritional
      status, socioeconomic status (SES), and level of maternal education. POPULATION
      AND METHODS: Blood pressure measurements and information on SES, level of
      maternal education, and body mass index of schoolchildren from the city of
      Cordoba, Argentina, were obtained. HBP was defined as systolic or diastolic blood
      pressure levels that are greater than or equal to the 95th percentile for a given
      age, sex, and height percentile at three consecutive measurements on separate
      days. RESULTS: A total of 1531 boys and girls participated; their average age was
      10.6 years. Fifty-five children had HBP. Systolic and diastolic blood pressure
      levels showed a significant association with obesity (p= 0.001), but not with age
      (p= 0.87), sex (systolic: p= 0.48; diastolic: p= 0.71) or SES (systolic: p= 0.07;
      diastolic: p= 0.09). CONCLUSIONS: The prevalence of HBP in a sample of
      schoolchildren from Argentina was 3.7%. It showed a significant association with
      obesity, but not with SES.

PMID- 30204986
TI  - Description of nutrient consumption based on the level of industrial food
      processing: national Survey on Nutrition and Health of2005.
AB  - Technological advances and changes in lifestyles reflect in a greater consumption
      of processed and ultra-processed foods compared to natural ones. Using data from
      the National Survey on Nutrition and Health, the consumption of these foods and
      their relation to living conditions were described in three age groups of
      Argentina (infants aged 6-23 months, children aged 2-5 years, and women aged 10
      49 years). Consumption among infants 6-23 months old is high in nutrients from
      natural foods: calcium (75.9%), proteins (72.7%), iron (71.5%), and fiber
      (68.9%). Among children 2-5 years old, consumption drops significantly. And among
      women, it drops even more. The proportion of the energy contribution from ultra
      processed foods is higher in the high-income population compared to the low
      income population across all groups.

PMID- 30204987
TI  - Applying art to scientific research: reasons for using an original method.
AB  - Art, by virtue of its symbolic power, may function as a cognitive instrument and
      even as an aid in the scientific research process, especially in the phase of
      hypothesis generation and data analysis given its ability to induce creative and
      intuitive thinking. In this article, we propose a method to put such concept into
      practice based on the exposure of scientists to collective artistic activities in
      protected settings, a methodology developed from the experiences described by
      renowned artists and scientists.

PMID- 30204988
TI  - Height, weight and body mass index of Wichi children from Formosa, Argentina.
AB  - This study provides the descriptive, anthropometric data of 194 children (aged 0
      18 years) from a Wichi population located in the province of Formosa, Argentina.
      The objective of this study was to document growth and nutritional status in this
      indigenous people. Weight, height, and body mass index data were collected and
      the corresponding Z-scores were estimated using national and international
      reference standards. Most analyzed parameters were within the normal range.
      However, it is concerning that a significant percentage of children are
      overweight, which may indicate that this population is going through a process of
      westernization that promotes the consumption of high-calorie, highly-processed
      foods and a lower level of physical activity.

PMID- 30204989
TI  - To believe or not to believe: is that the question?
AB  - It is a reality that, in the field of pediatrics, parents are the legal
      representatives of their children, which means that any medical decision in
      relation to the child should be taken with the intercession of at least one of
      his/her parents who -in the exercise of a subrogated autonomy and a legally
      granted representation- provide their informed consent. The problem arises when
      the parents refuse to give their informed consent or directly make decisions that
      will have a specific impact on their child's well-being, thus causing damage or
      at least a risk for damage. The challenge here is to reconcile the interests and
      rights at stake, always considering that the constitutional rule of
      interpretation in the case of a child are his/her best interests.

PMID- 30204990
TI  - Beckwith-Wiedemann syndrome: clinical and etiopathogenic aspects of a model
      genomic imprinting entity.
AB  - The Beckwith-Wiedemann syndrome is the most common genetic entity in overgrowth,
      with an approximate incidence of 1 in 10 00013 700births. Its broad clinical
      spectrum includes pre- and postnatal macrosomia, macroglossia, pinna
      abnormalities, abdominal wall defects, visceromegaly, and hyperinsulinemic
      hypoglycemia. This syndrome predisposes to childhood cancer and is caused by
      diverse genetic and/or epigenetic disorders that usually affect the regulation of
      genes imprinted on chromosome 11p15.5. The knowledge of (epi) genotype-phenotype
      correlations has prompted recommendations to propose different health care
      strategies, including tumor surveillance protocols based on molecular
      classification, aimed at standardizing clinical practice. The objective of this
      article is to describe the current status of the Beckwith-Wiedemann syndrome, a
      model of genomic imprinting.

PMID- 30204991
TI  - Gastrointestinal evaluation in colchicine-treated familial Mediterranean fever
      patients with chronic abdominal pain: cases series.

PMID- 30204992
TI  - [Importance of the exhaustive anamnesis to an unexplained unilateral gynecomastia
      in a child].
AB  - Gynecomastia consists of breast enlargement due to a hormonal imbalance between
      estrogens and androgens. Unilateral and important breast growth requires ruling
      underlying pathologic disorders out. Mechanical cause is uncommon, causing
      enlargement by repeated stimulation. We report a 6-year-old boy with unilateral
      gynecomastia. Hyperprolactinemia is the only abnormal finding at laboratory
      tests. After repeated inquiries, a continuous breast selfstimulation is detected.
      Its relation with gynecomastia is verified because prolactin normalizes and
      breast regressed in further revisions, after stopping stimulus.

PMID- 30204993
TI  - [Coinfection by astrovirus and Neisseria B meningitidis in a girl].
AB  - Meningococcal infection associates high morbidity and mortality. Viral
      coinfection has been described mainly with herpes and respiratory virus. We
      describe a child who suffered a tonic-clonic seizure with hypotension,
      tachycardia and low Glasgow Coma Scale. She maintained an altered mental status
      and required hemodynamic stabilization in the Pediatric Intensive Care Unit. Wide
      spectrum antibiotherapy was initiated. She suffered large and foul-smelling
      liquid not bloody stools which were cultured and studied by polymerase chain
      reaction. The cerebrospinal fluid was normal. Later the polymerase chain reaction
      stools were positive to astrovirus, and the blood polymerase chain reaction was
      positive to Neisseria meningitidis group B. As far as we know, this is the first
      case of astrovirus and Neisseria meningitidis coinfection described in children.
      This virus should be considered as new cause of viral coinfection to discard if
      unexplained abdominal pain or vomits and liquid stools are observed.

PMID- 30204994
TI  - Successful fluconazole treatment of catheter-related candidemia caused by Candida
      haemulonii: report of 2 neonatal cases.
AB  - Candida haemulonii forms part of the non-albicans Candida species. The candidemia
      caused by C. haemulonii is extremely rare but fatal in neonates. We reported the
      first two neonates with C. haemulonii candidemia in China which were treated with
      fluconazole and reviewed two papers previously reported. Our report adds further
      awareness on C. haemulonii candidemia in critical neonates and points out the
      importance of an early diagnosis and treatment of this fatal infection.

PMID- 30204996
TI  - [Sweet syndrome in a 5-year-old girl].
AB  - Sweet syndrome, also known as acute febrile neutrophilic dermatosis, is an
      infrequent dermatological disorder in pediatrics. Clinically it is characterized
      by the development of papular and/or nodular lesions of a reddish-violet
      coloration with local hypersensitivity. We report the case of a 5-year-old female
      who consulted 1 month after the appearance of the lesion in the nasal arch. A
      skin biopsy was performed and it reported diffuse dermatitis with a predominance
      of neutrophil polymorphonuclear cells, epidermal necrosis and absence of
      vasculitis. No microorganisms were identified. It was considered compatible with
      Sweet syndrome. It is important to consider this diagnosis in similar clinical
      cases and other more frequent diagnoses must be ruled out first.

PMID- 30204995
TI  - [Diencephalic syndrome in a child with chronic malnutrition and hyperactivity].
AB  - Diencephalic syndrome is an infrequent cause of malnutrition. It is produced by a
      malfunctioning hypothalamus, and it is related to encephalic tumors. Patients
      present a serious and progressive weight loss although the appetite and calorie
      intake are, usually, adequate. Neurological symptoms typically have a late
      appearance, delaying diagnostic suspicion. We present a patient aged 2 years and
      a half with grade II chronic malnutrition, referred with presumptive diagnosis of
      celiac disease, with poor adherence and treatment failure. During
      hospitalization, diagnosis of diencephalic syndrome secondary to grade I
      pilocytic astrocytoma was reached.

PMID- 30204997
TI  - [Neonatal diagnosis of unilateral renal artery stenosis].
AB  - Renal artery stenosis represents a rare cause of neonatal arterial hypertension
      of renovascular origin, having been described few cases in the literature at this
      stage of life. Most patients with this disease remain asymptomatic; hypertension
      can be detected in routine pediatric revisions. Diagnosis can be performed by
      combining biochemical and radiological findings. The initial management consists
      of pharmacological therapy in order to achieve adequate growth. Subsequently, it
      is necessary to assess definitive repair of the vascular lesion or nephrectomy in
      the case of functional abolition of the affected kidney. We present a term
      newborn female, with arterial hypertension and an important congestive heart
      failure, caused by a unilateral renal artery stenosis, with functional abolition
      and atrophy of the affected kidney, which required an important inotropic and
      antihypertensive support during her first days of life, with significant clinical
      improvement subsequently.

PMID- 30204998
TI  - [Chronic recurrent multifocal osteomyelitis: pediatric clinical case].
AB  - Chronic recurrent multifocal osteomyelitis has recently been classified as an
      autoinflammatory disorder characterized by episodes of systemic inflammation
      including serological signs of inflammation occurring in the absence of
      autoantibodies or pathogen agents. The insidious onset of pain with swelling and
      tenderness localized over the affected bones are the main manifestations. The
      metaphysis and epiphyses of the long bones, clavicle and vertebrae are affected.
      We report a male patient aged 2 years and 2 months with osteomyelitis with lytic
      destruction in two different single sites with a year difference between the
      episodes. Histological examination of the bone showed inflammation and chronic
      osteomyelitis, excluding the existence of infectious osteomyelitis, neoplasm and
      myeloproliferative disease. Clinical symptoms improved under treatment with
      nonsteroidal anti-inflammatory drugs. Considering chronic recurrent multifocal
      osteomyelitis may shorten time to diagnosis in order to avoid potentially
      unnecessary prolonged courses of intravenous antibiotics, complementary studies
      and multiple biopsies.

PMID- 30204999
TI  - Scurvy due to restrictive diet in a child with autism spectrum disorder: case
      report.
AB  - Scurvy is a very uncommon entity in pediatric population. Some case reports have
      been published in infants fed with boiled milk, in patients with iron overload
      secondary to hematological diseases and in children with food restrictions
      secondary to neurodevelopmental disorders. We report a case of a 4-year-old male
      patient with a diagnosis of autism spectrum disorder, which developed scurvy
      secondary to a long-term selective eating habit without fruit or vegetable
      intake. The objective of this case report is to announce the pediatrician and
      other professionals dedicated to primary health care about scurvy as a potential
      consequence of restrictive diets in children with autism spectrum disorders as
      well as the importance of dietary history in sick patients to prevent associated
      micronutrient deficiencies.

PMID- 30205000
TI  - [Combined glomerulopathies: two pediatric cases].
AB  - Combined glomerulopathy is infrequent in pediatric patients. Its presence should
      be suspected in those patients with glomerulophaties with atypical course. The
      influence on the long-term renal impairment remains uncertain. Here we report two
      children with histological findings of combined glomerulopathy.

PMID- 30205001
TI  - Synthesis and Evaluation of New Bifunctional Chelators with Phosphonic Acid Arms
      for Gallium-68 Based PET Imaging in Melanoma.
AB  - Due to the increasing use of generator-produced radiometal Gallium-68 (68Ga) in
      positron-emission tomography/computed tomography (PET/CT), reliable bifunctional
      chelators that can efficiently incorporate 68Ga3+ into biomolecules are highly
      desirable. In this study, we synthesized two new bifunctional chelators bearing
      one or two phosphonic acid functional groups, named p-SCN-PhPr-NE2A1P and p-SCN
      PhPr-NE2P1A, with the aim of enabling facile production of 68Ga-based
      radiopharmaceuticals. Both chelators were successfully conjugated to LLP2A-PEG4,
      a very late antigen-4 (VLA-4) targeting peptidomimetic ligand, to evaluate their
      application in 68Ga-based PET imaging. NE2P1A-PEG4-LLP2A exhibited the highest
      68Ga3+ binding ability with molar activity of 37 MBq/nmol under mild temperature
      and neutral pH. Excellent serum stability of 68Ga-NE2P1A-PEG4-LLP2A was observed,
      which was consistent with the result obtained from density functional theory
      calculation. The in vitro cell study showed that 68Ga-NE2P1A-PEG4-LLP2A had
      significantly longer retention in B16F10 cells comparing to the reported
      retention of 64Cu-NE3TA-PEG4-LLP2A, although the uptake was relatively lower. In
      the biodistribution and micro-PET/CT imaging studies, high tumor uptake and low
      background were observed after 68Ga-NE2P1A-PEG4-LLP2A was injected into mice
      bearing B16F10 tumor xenografts, making it a highly promising radiotracer for
      noninvasive imaging of VLA-4 receptors overexpressed in melanoma.

PMID- 30205002
TI  - Bi(OTf)3-Catalyzed Diastereoselective One-Pot Synthesis of 1,3-Diamines with
      Three Continuous Stereogenic Centers.
AB  - A highly modular, diastereoselective one-pot-synthesis of 1,3-diamines with three
      contiguous stereogenic centers is reported. Our method provides a fast and
      efficient access to 1,2- anti-2,3- anti-1,3-diamines from three readily available
      building blocks. This Bi(OTf)3-catalyzed reaction is insensitive to air and
      moisture and can be performed on a multigram scale.

PMID- 30205003
TI  - Crop Protection Discovery: Is Being the First Best?
AB  - Current crop protection chemicals span an array of chemistry classes and modes of
      action. Typically, within each chemistry class, there are multiple chemically
      distinct active ingredients competing with each other for market position. In
      this competition, the first product to market in a new class or mode of action
      may or may not have an advantage depending upon a number of parameters, including
      relative efficacy against the target pests, pest resistance, regulatory
      pressures, synthetic complexity, and marketing effectiveness. The number of
      companies involved in the discovery of new crop protection compounds has been
      declining, and patenting strategies have become more sophisticated, making it
      more challenging to break into an existing area of chemistry. One result is new
      classes of chemistry tend to be smaller, making first to market more beneficial
      than in the past. Additionally, the first into a market with a new class of
      chemistry has the opportunity to set positioning and expectations.

PMID- 30205004
TI  - Aggregation-Induced Emission Luminogens as Color Converters for Visible-Light
      Communication.
AB  - In this work, we report the application of the aggregation-induced emission
      luminogens (AIEgens) as color converters for visible light communication (VLC).
      In the form of pure solid powder, the AIEgens studied herein have demonstrated
      blue-to-red full-color emissions, large -6 dB electrical modulation bandwidths up
      to 279 MHz (~56* that of commercial phosphor), and most of them can achieve high
      data rates of 428-493 Mbps (up to ~49* that of commercial phosphor) at a maximum
      bit error rate of 3.8 * 10-3 using on-off keying. Their data communication
      performances strongly suggest that AIEgens are very promising candidates as color
      converters for VLC applications, together with their unique AIE properties that
      will benefit usage in high concentration. Based on the comprehensive experimental
      results, we further propose some insights into improving data rate of the color
      converter in VLC: the data rate limit is influenced by modulation bandwidth and
      signal-noise ratio (SNR). We have experimentally proved that the -6 dB electrical
      modulation bandwidth f c can be estimated from the effective lifetime tau of the
      color converter with the theoretical prediction of [Formula: see text] within
      experimental uncertainties, while theoretically derived that the SNR is
      proportional to its PL quantum efficiency. These observations and implications
      are very profound for exploring materials as color converters and improve the
      data transmission performance in VLC.

PMID- 30205005
TI  - Discovery and Structure-Based Optimization of Benzimidazole-Derived Activators of
      SOS1-Mediated Nucleotide Exchange on RAS.
AB  - Son of sevenless homologue 1 (SOS1) is a guanine nucleotide exchange factor that
      catalyzes the exchange of GDP for GTP on RAS. In its active form, GTP-bound RAS
      is responsible for numerous critical cellular processes. Aberrant RAS activity is
      involved in ~30% of all human cancers; hence, SOS1 is an attractive therapeutic
      target for its role in modulating RAS activation. Here, we describe a new series
      of benzimidazole-derived SOS1 agonists. Using structure-guided design, we
      discovered small molecules that increase nucleotide exchange on RAS in vitro at
      submicromolar concentrations, bind to SOS1 with low double-digit nanomolar
      affinity, rapidly enhance cellular RAS-GTP levels, and invoke biphasic signaling
      changes in phosphorylation of ERK 1/2. These compounds represent the most potent
      series of SOS1 agonists reported to date.

PMID- 30205006
TI  - Near-Infrared Spectroscopy and Anharmonic Theory of Protonated Water Clusters:
      Higher Elevations in the Hydrogen Bonding Landscape.
AB  - Near-infrared spectroscopy measurements are presented for protonated water
      clusters, H+(H2O) n, in the size range of n = 1-8. Clusters are produced in a
      pulsed-discharge supersonic expansion, mass selected, and studied with infrared
      laser photodissociation spectroscopy in the regions of 3600-4550 and 4850-7350 cm
      1. Although there is some variation with cluster size, the main features of these
      spectra are a broad absorption near 5300 cm-1, a sharp doublet near 7200 cm-1, as
      well as a structured absorption near 4100 cm-1 for n >= 2. The vibrational
      patterns measured for the hydronium, Zundel, and Eigen ions are compared to those
      predicted by different forms of anharmonic theory. Second-order vibrational
      perturbation theory (VPT2) and a local mode treatment of the OH stretches both
      capture key aspects of the spectra but suffer understandable deficiencies in the
      quantitative description of band positions and intensities.

PMID- 30205007
TI  - An Ultra-Low-Friction Triboelectric-Electromagnetic Hybrid Nanogenerator for
      Rotation Energy Harvesting and Self-Powered Wind Speed Sensor.
AB  - Triboelectric nanogenerators (TENGs) are attracting more and more attention since
      they can convert various mechanical energies into electric energy. However, in
      traditional TENGs for harvesting rotation energy, most of the contacts between
      two triboelectric materials are rigid-to-rigid contact with very large friction
      force, which limits their practical application. Here, we report an ultra-low
      friction triboelectric-electromagnetic hybrid nanogenerator (NG). A freestanding
      mode TENG and a rotating electromagnetic generator (EMG) are integrated together
      to realize the complementary individual merits. The very soft and elastic contact
      between the two triboelectric materials in the TENG results into very small
      friction force. The influences of the type and the dimensions of the dielectric
      material on the performance of the TENG are studied systematically from theory to
      experiments. The results indicate that the open-circuit voltage and the transfer
      charge of the TENG increase with the rotation speed, which is very different from
      a traditional rotary TENG and is due to the increase of the contact area. The
      optimized TENG has a maximal load voltage of 65 V and maximal load power per unit
      mass of 438.9 mW/kg under a speed rotation of 1000 rpm, while the EMG has a
      maximal load voltage of 7 V and maximal load power density of 181 mW/kg. This
      demonstration shows that the hybrid NG can power a humidity/temperature sensor by
      converting wind energy into electric energy when the wind speed is 5.7 m/s.
      Meanwhile, it can be used as a self-powered wind speed sensor to detect wind
      speed as low as 3.5 m/s.

PMID- 30205008
TI  - Improving Accuracy and Confidence of Chemical Identification by Gas
      Chromatography/Vacuum Ultraviolet Spectroscopy-Mass Spectrometry: Parallel Gas
      Chromatography, Vacuum Ultraviolet, and Mass Spectrometry Library Searches.
AB  - Chemical identification often relies on matching measured chemical properties
      and/or spectral "fingerprints" of unknowns against their precompiled libraries.
      Chromatography, absorption spectroscopy, and mass spectrometry are all among
      analytical approaches that provide chemical measurement databases amenable to
      library searching. Occasionally, using conventional single-library or single
      domain searches can lead to misidentification of unknowns. To improve chemical
      identification, we present a tandem gas chromatography/vacuum ultraviolet-mass
      spectrometry (GC/VUV-MS) chemical identification approach that utilizes databases
      from GC, VUV spectroscopy, and mass spectrometry analyses for a "multidomain"
      library search. Using standard chemical mixtures as well as aroma compounds as
      test cases, we demonstrate that multidatabase library searches utilizing GC, VUV,
      and MS data results in fully correct identification of chemical mixtures examined
      here that could only be identified with a 69.2% or an 88.5% success rate with MS
      or VUV library searches alone, respectively. Additionally, we introduce a library
      and data domain-independent metric for evaluating the confidence of library
      search results. Using multidomain library searches improves both the chemical
      assignment accuracy and confidence.

PMID- 30205009
TI  - Synthesis of Five-Membered Iodine-Nitrogen Heterocycles from Benzimidazole-Based
      Iodonium Salts.
AB  - Pseudocyclic 2-benzimidazolyl-substituted diaryliodonium salts were obtained by
      the reaction of the corresponding [hydroxy(tosyloxy)iodo]arenes with arenes in
      the presence of trifluoromethanesulfonic acid. X-ray structural analysis of these
      iodonium salts confirmed their pseudocyclic structure with a short (2.57-2.58 A)
      noncovalent I...N interaction. Treatment of 2-benzimidazolyl-substituted
      diaryliodonium triflates with a base afforded novel five-membered iodine-nitrogen
      heterocycles.

PMID- 30205010
TI  - VUV Photodeposition of Thiol-Terminated Films: A Wavelength-Dependent Study.
AB  - Photoinitiated chemical vapor deposition (PICVD) has become attractive for
      selective and specific surface functionalization, because it relies on a single
      energy source, the photons, to carry out (photo-) chemistry. In the present
      wavelength (lambda)-dependent study, thiol (SH)-terminated thin film deposits
      have been prepared from gas mixtures of acetylene (C2H2) and hydrogen sulfide
      (H2S) via PICVD using four different vacuum-ultraviolet (VUV) sources, namely,
      KrL (lambdapeak = 123.6 nm), XeL (lambdapeak = 147.0 nm), XeE (lambdapeak = 172.0
      nm), and Hg (lambda = 184.9 nm) lamps. Different lambda influence the deposition
      kinetics and film composition, reflecting that photolytic reactions are governed
      by the gases' absorption coefficients, k(lambda). Thiol concentrations, [SH], up
      to ~7.7%, were obtained with the XeL source, the highest reported in the
      literature so far. Furthermore, all films showed islandlike surface morphology,
      regardless of lambda.

PMID- 30205011
TI  - Hybrid III-V/IV Nanowires: High-Quality Ge Shell Epitaxy on GaAs Cores.
AB  - The integration of optically active III-V and electronic-suitable IV materials on
      the same nanowire could provide a great potential for the combination of
      photonics and electronics in the nanoscale. In this Letter, we demonstrate the
      growth of GaAs/Ge core-shell nanowires on Si substrates by molecular beam epitaxy
      and investigate the radial and axial Ge epitaxy on GaAs nanowires in detail. High
      quality core-shell nanowires with smooth side facets and dislocation-free, sharp
      interfaces are achieved. It is found that the low shell growth temperature leads
      to smoother side facets, while higher shell growth temperatures lead to more
      relaxed structures with significantly faceted sidewalls. The possibility of
      forming a III-V/IV heterostructure nanowire with a Ge section development in the
      axial direction of a GaAs nanowire using a Ga droplet is also revealed. These
      nanowires provide an ideal platform for nanoscale III-V/IV combination, which is
      promising for highly integrated photonic and electronic hybrid devices on a
      single chip.

PMID- 30205012
TI  - Prolonged amino acid infusion into intrauterine growth restricted fetal sheep
      increases leucine oxidation rates.
AB  - Overcoming impaired growth in an intrauterine growth restricted (IUGR) fetus has
      potential to improve neonatal morbidity, long-term growth, and metabolic health
      outcomes. The extent to which fetal anabolic capacity persists as the IUGR
      condition progresses is not known. We tested whether prolonged amino acid
      infusion would increase protein accretion in the IUGR fetus produced from chronic
      placental insufficiency. IUGR fetal sheep were infused for 10 days with either
      mixed amino acids providing ~2 g.kg-1.day-1 (IUGR-AA) or saline (IUGR-Sal) during
      late gestation. At the end of the infusion, fetal plasma leucine, isoleucine,
      lysine, methionine, and arginine concentrations were higher in IUGR-AA vs. IUGR
      Sal (P<0.05). Fetal plasma glucose, oxygen, insulin, IGF-1, cortisol, and
      norepinephrine concentrations were similar between IUGR groups, but glucagon
      concentrations were 4-fold higher in IUGR-AA (P<0.05). Net umbilical amino acid
      uptake rate did not differ between IUGR groups; thus, the total amino acid
      delivery rate (net umbilical amino acid uptake plus infusion rate) was higher in
      IUGR-AA (IUGR-AA 30 +/- 4, IUGR-Sal 19 +/- 1 MUmol.kg-1.min-1, P<0.05). Net
      umbilical glucose, lactate, and oxygen uptake rates were similar between IUGR
      groups. Fetal leucine oxidation rate measured using a leucine tracer was higher
      in IUGR-AA (IUGR-AA 2.5 +/- 0.3, IUGR-Sal 1.7 +/- 0.3 MUmol.kg-1.min-1, P<0.05).
      Fetal protein accretion rate was not statistically different between the IUGR
      groups due to variability in response to amino acids (IUGR-AA 1.6 +/- 0.4, IUGR
      Sal 0.8 +/- 0.3 MUmol.kg-1.min-1). Prolonged amino acid infusion into IUGR fetal
      sheep increased leucine oxidation rates with variable anabolic response.

PMID- 30205013
TI  - Etiology and Pathogenesis of Hemifacial Microsomia.
AB  - Hemifacial microsomia (HFM) is a common congenital malformation of the
      craniofacial region. There are 3 possible pathogenic models of HFM-vascular
      abnormality and hemorrhage in the craniofacial region, damage to Meckel's
      cartilage, and the abnormal development of cranial neural crest cells-and the
      most plausible hypothesis is the vascular abnormality and hemorrhage model. These
      3 models are interrelated, and none of them is completely concordant with all the
      variable manifestations of HFM. External environmental factors (e.g.,
      thalidomide, triazene, retinoic acid, and vasoactive medications), maternal
      intrinsic factors (e.g., maternal diabetes), and genetic factors (e.g., the
      recently reported mutations in OTX2, PLCD3, and MYT1) may lead to HFM through >=1
      of these pathogenic processes. Whole genome sequencing to identify additional
      pathogenic variants, biological functional studies to understand the exact
      molecular mechanisms, and additional animal model and clinical studies with large
      stratified samples to elucidate the pathogenesis of HFM will be necessary. Small
      molecule drugs, as well as CRISPR/CAS9-based genetic interventions, for the
      prevention and treatment of HFM may also be a future research hotspot.

PMID- 30205014
TI  - Vitamin D potentiates anti-tumor activity of 5-fluorouracil via modulating
      caspase-3 and TGF-beta1 expression in hepatocellular carcinoma-induced in rats.
AB  - We investigated the role of vitamin D (Vit D) alone and in combination with 5
      fluorouracil (5-FU) in thioacetamide (TAA)-induced hepatocellular carcinoma (HCC)
      in rats. Fifty male Sprague-Dawley rats were randomized into a control group and
      4 groups that received TAA (200 mg/kg, i.p.) twice per week for 16 weeks. These 4
      groups were further divided as follows: HCC group; 5-FU group (75 mg/kg, i.p.,
      once weekly for 3 weeks starting from the 12th week); Vit D group (200 IU/kg
      daily by oral tube for 16 weeks); and 5-FU + Vit D group (received the previously
      mentioned dosage regimens of 5-FU and Vit D). HCC was detected by
      histopathological changes in liver sections and the elevation of serum alpha
      fetoprotein (AFP). Treatment with 5-FU + Vit D significantly decreased gene
      expression of nuclear factor erythroid 2-related factor 2 (NrF2) and transforming
      growth factor beta1 (TGF-beta1) at both the gene and protein level and serum AFP
      concentrations in comparison with their corresponding monotherapy. Moreover, 5-FU
      + Vit D treatment enhanced apoptosis by increasing caspase-3 gene and protein
      expression. Conclusively, Vit D enhances antitumor activity of 5-FU in an HCC
      induced model and improves liver function of treated animals. Combination therapy
      in a TAA-induced HCC rat model was more effective than 5-FU or Vit D through the
      modulation of TGF-beta1, caspase-3, and NrF2 expressions.

PMID- 30205015
TI  - Multidisciplinary approaches for studying rhizobium-legume symbioses.
AB  - The rhizobium-legume symbiosis is a major source of fixed nitrogen (ammonia) in
      the biosphere. The potential for this process to increase agricultural yield
      while reducing the reliance on nitrogen-based fertilizers has generated interest
      in understanding and manipulating this process. For decades, rhizobium research
      has benefited from the use of leading techniques from a very broad set of fields,
      including population genetics, molecular genetics, genomics, and systems biology.
      In this review, we summarize many of the research strategies that have been
      employed in the study of rhizobia and the unique knowledge gained from these
      diverse tools, with a focus on genome- and systems-level approaches. We then
      describe ongoing synthetic biology approaches aimed at improving existing
      symbioses or engineering completely new symbiotic interactions. The review
      concludes with our perspective of the future directions and challenges of the
      field, with an emphasis on how the application of a multidisciplinary approach
      and the development of new methods will be necessary to ensure successful
      biotechnological manipulation of the symbiosis.

PMID- 30205016
TI  - Predicting Caries in Medical Settings: Risk Factors in Diverse Infant Groups.
AB  - Expanded partnership with the medical community is a promising strategy for
      reducing disparities in dental caries among young children. However, no validated
      caries risk instrument exists for use in primary health care settings. To help
      resolve this gap, a 52-item caries risk questionnaire was developed and targeted
      to primary caregivers (PCGs) to test in a 3-y prospective study. To begin to
      understand the validity of the questionnaire items, the purpose of this study was
      to compare responses to the questionnaire based on key demographic
      characteristics known to be associated with disparities in caries experience
      (e.g., race/ethnicity and insurance status). A total of 1,323 one-year-old
      children were recruited primarily through 3 medical research networks. Baseline
      questionnaire responses were analyzed via logistic regression. The sample was 49%
      female. Its racial/ethnic makeup was as follows: 13% Hispanic, 37% White, 37%
      Black, and 13% other or multiracial. Sixty-one percent were enrolled in Medicaid,
      and 95% resided in urban communities. Mothers represented 94% of PCGs. There were
      significant differences ( P < 0.05) in baseline responses based on Medicaid
      status and race/ethnicity. As compared with those not enrolled in Medicaid,
      children in the Medicaid group were significantly more likely (after adjusting
      for race/ethnicity) to 1) go to sleep while nursing or drinking something other
      than water, 2) eat sugary snacks between meals, 3) consume sugary drinks between
      meals, 4) receive topical fluoride from a health professional, 5) visit the
      dentist, and 6) not have an employed adult in the household. PCGs of children
      enrolled in Medicaid were significantly more likely to be the mother, have
      bleeding gums, eat sugary snacks between meals, consume sugary drinks between
      meals, eat or drink something other than water before going to bed, and not get
      regular dental checkups. In conclusion, there are significant differences in
      caries risk questionnaire responses based on Medicaid status and race/ethnicity
      that provide construct and criterion validity to the developed caries risk tool
      (ClinicalTrials.gov NCT01707797).

PMID- 30205017
TI  - Pulse wave reflection responses to bench press with and without practical blood
      flow restriction.
AB  - : Resistance exercise is recommended to increase muscular strength, but may also
      increase pulse wave reflection. Resistance exercise combined with practical blood
      flow restriction (pBFR) on pulse wave reflection is unknown. PURPOSE: To evaluate
      the differences between bench press with pBFR and traditional high-load bench
      press on pulse wave reflection characteristics in resistance-trained men.
      METHODS: Sixteen resistance-trained men participated in the study. Pulse wave
      reflection characteristics were assessed before and after low-load bench press
      with pBFR (LL-pBFR), traditional high-load bench press (HL), and a control (CON).
      A repeated measures ANOVA was used to evaluate the conditions across time on
      pulse wave reflection characteristics. RESULTS: There were significant (p<=0.05)
      interactions for heart rate, augmentation index, augmentation index normalized at
      75bpm, augmentation pressure, time-tension index and wasted left ventricular
      energy such that they were increased after LL-pBFR and HL compared to rest and
      CON, with no differences between LL-pBFR and HL. Aortic pulse pressure (p<0.001)
      was only elevated after LL-pBFR compared to rest. In addition, there was a
      significant (p<=0.05) interaction for aortic diastolic blood pressure (BP) such
      that it was decreased after LL-pBFR compared to rest and CON but not HL. The
      subendocardial viability ratio and diastolic-pressure-time index were
      significantly different between LL-pBFR and HL compared to rest and CON. There
      were no significant interactions for brachial systolic or diastolic BP, aortic
      systolic BP, or time of the reflected wave. CONCLUSION: Acute bench press
      resistance exercise using LL-pBFR or HL, significantly altered pulse wave
      reflection characteristics without differences between LL-pBFR and HL.

PMID- 30205019
TI  - Effect of Polarization and Chronic Inflammation on Macrophage Expression of
      Heparan Sulfate Proteoglycans and Biosynthesis Enzymes.
AB  - Heparan sulfate (HS) proteoglycans on immune cells have the ability to bind to
      and regulate the bioactivity more than 400 bioactive protein ligands, including
      many chemokines, cytokines, and growth factors. This makes them important
      regulators of the phenotype and behavior of immune cells. Here we review how HS
      biosynthesis in macrophages is regulated during polarization and in chronic
      inflammatory diseases such as rheumatoid arthritis, atherosclerosis, asthma,
      chronic obstructive pulmonary disease and obesity, by analyzing published micro
      array data and mechanistic studies in this area. We describe that macrophage
      expression of many HS biosynthesis and core proteins is strongly regulated by
      macrophage polarization, and that these expression patterns are recapitulated in
      chronic inflammation. Such changes in HS biosynthetic enzyme expression are
      likely to have a significant impact on the phenotype of macrophages in chronic
      inflammatory diseases by altering their interactions with chemokines, cytokines,
      and growth factors.

PMID- 30205020
TI  - A Prospective, Controlled, Multicenter Study to Evaluate the Clinical Outcome of
      Implant Treatment in Women with Osteoporosis/Osteopenia: 5-Year Results.
AB  - The impact of osteoporosis on implant treatment is still a matter of debate in
      the scientific community, as it may possibly lead to higher failure rates. As
      long-term controlled trials are missing, the aim of this study was to verify the
      long-term outcome of implants placed in patients with systemic osteoporosis.
      Postmenopausal women in need of implants underwent bone mineral density
      measurements in hip and spine, using dual X-ray absorptiometry scans. Based on T
      scores, they were divided into 2 groups: group O (osteoporosis group) with a T
      score <=-2 or group C (control group) with a T-score of >=-1. Implants were
      placed in a 2-stage manner and loaded 4 to 8 wk after abutment surgery. Six
      months after loading and thereafter yearly, clinical and radiographical
      parameters were assessed. In total, 148 implants were placed in 48 patients (mean
      age: 67 y [range, 59-83]). Sixty-three implants were placed in 20 patients (group
      O) and 85 implants in 28 patients (group C). After 5 y, 117 implants (38 in group
      O and 79 in the group C) in 37 patients were assessed. Cumulative survival rate
      on an implant level was 96.5% (group O: 91.5%; group C: 100.0% [ P < 0.05]) and
      95.7% (group O: 89.2%; group C: 100.0% [ P > 0.05]) on a patient level. The
      overall marginal bone-level alterations, after 5 y of loading, were -0.09 +/-
      0.78 mm (group O: -0.15 +/- 0.50 mm; group C: -0.06 +/- 0.89 mm) on an implant
      level and -0.09 +/- 0.54 mm (group O: -0.18 +/- 0.43 mm; group C: 0.06 +/- 0.58
      mm) on a patient level ( P > 0.05). Oral implant therapy in osteoporotic patients
      is a reliable treatment option with comparable osseointegration rates, implant
      survival, and marginal bone-level alterations after 5 y of functional loading
      (ClinicalTrials.gov NCT00745121).

PMID- 30205021
TI  - Environmental Stress Increases the Magnitude of Nonadditive Genetic Variation in
      Offspring Fitness in the Frog Crinia georgiana.
AB  - When organisms encounter heterogeneous environments, selection may favor the
      ability of individuals to tailor their phenotypes to suit the prevailing
      conditions. Understanding the genetic basis of plastic responses is therefore
      vital for predicting whether susceptible populations can adapt and persist under
      new selection pressures. Here, we investigated whether there is potential for
      adaptive plasticity in development time in the quacking frog Crinia georgiana, a
      species experiencing a drying climate. Using a North Carolina II breeding design,
      we exposed 90 family groups to two water depth treatments (baseline and low
      water) late in larval development. We then estimated the contribution of additive
      and nonadditive sources of genetic variation to early offspring fitness under
      both environments. Our results revealed a marked decline in larval fitness under
      the stressful (low water) rearing environment but also that additive genetic
      variation was negligible for all traits. However, in most cases, we found
      significant sire-by-dam interactions, indicating the importance of nonadditive
      genetic variation for offspring fitness. Moreover, sire-by-dam interactions were
      modified by the treatment, indicating that patterns of nonadditive genetic
      variance depend on environmental context. For all traits, we found higher levels
      of nonadditive genetic variation (relative to total phenotypic variation) when
      larvae were reared under stressful conditions, suggesting that the fitness costs
      associated with incompatible parental crosses (e.g., homozygous deleterious
      recessive alleles) will only be expressed when water availability is low. Taken
      together, our results highlight the need to consider patterns of nonadditive
      genetic variation under contrasting selective regimes when considering the
      resilience of species to environmental change.

PMID- 30205018
TI  - Sexual Dimorphism in Immunity to Oral Bacterial Diseases: Intersection of
      Neutrophil and Osteoclast Pathobiology.
AB  - Sex is a biological variable that affects immune responses to bacterial and other
      types of infectious agents. Males and females are known to have differential oral
      bacterial disease burden in periodontal and endodontic disease. Understanding
      that there is a contribution from both sex and gender to these oral diseases, we
      discuss in this review recent sex-based findings that provide a pathobiological
      basis for differences observed between males and females. Sexual dimorphism of
      immune responses with respect to neutrophil trafficking and osteoclast
      differentiation and formation is presented as a plausible mechanism to explain
      the sexual differences. We also emphasize that sex, as a biological variable,
      should be considered in these types of oral immunologic studies.

PMID- 30205022
TI  - The Role of Geography in Adaptive Radiation.
AB  - Although the importance of biogeography in the speciation process is well
      recognized, the fundamental role of geographic diversification during adaptive
      radiations has not been studied to determine its importance during the adaptive
      radiation process. We examined the relationship between lineage and regional
      diversification patterns in the South American rodent subfamily Sigmodontinae,
      one of the best candidates for an adaptive radiation in mammals, to propose a
      conceptual framework for geographic transitions during adaptive radiations. We
      reconstructed a time-calibrated phylogeny from four nuclear genes and one
      mitochondrial gene for 77% of sigmodontine diversity. Historical biogeography was
      reconstructed among 14 regions, for which we applied a sliding-window approach to
      estimate regional transition rates through time. We compared these rate patterns
      and measured whether regions consisted of species that were more phylogenetically
      related than expected by chance. Following the initial South American
      colonization around 7 million years ago, multiple expansions from northern
      regions correlated with a burst of speciation. Subsequently, both diversification
      and regional transition rates decreased overall and within the majority of
      regions. Despite high regional transition rates, nearly all regional assemblages
      were phylogenetically clustered, indicating that within-region diversification
      was common. We conclude that biogeographic complexity and partitioning played a
      profound role in the adaptive radiation of the South American Sigmodontinae
      (Oryzomyalia), the degree to which is determined by the relative scales of
      spatial variation and dispersal abilities.

PMID- 30205023
TI  - Competition and Stragglers as Mediators of Developmental Synchrony in Periodical
      Cicadas.
AB  - Periodical cicadas are enigmatic organisms: broods spanning large spatial ranges
      consist of developmentally synchronized populations of 3-4 sympatric species that
      emerge as adults every 13 or 17 years. Only one brood typically occupies any
      single location, with well-defined boundaries separating distinct broods. The
      cause of such synchronous development remains uncertain, but it is known that
      synchronous emergence of large numbers of adults in a single year satiates
      predators, allowing a substantial fraction of emerging adults to survive long
      enough to reproduce. Competition among nymphs feeding on tree roots almost
      certainly plays a role in limiting populations. However, due to the difficulty of
      working with such long-lived subterranean life stages, the mechanisms governing
      competition in periodical cicadas have not been identified. A second process that
      may affect synchrony among periodical cicadas is their ability to delay or
      accelerate their emergence as adults by 1 year and accelerate it by 4 years
      (stragglers). We develop a nonlinear Leslie matrix-type model that describes
      cicada dynamics accounting for predation, competition, and stragglers. Using
      numerical simulations, we identify conditions that generate dynamics in which a
      single brood occupies a given geographical location. Our results show that while
      stragglers have the potential for introducing multiple sympatric broods, the
      interaction of interbrood competition with predation-driven Allee effects creates
      a system resistant to such invasions, and populations maintain developmental
      synchrony.

PMID- 30205024
TI  - On the Interplay among Ambient Temperature, Basal Metabolic Rate, and Body Mass.
AB  - One of the most generalized conclusions arising from studies analyzing the
      ecological variation of energy metabolism in endotherms is the apparent negative
      correlation between ambient temperature and mass-independent basal metabolic rate
      (residual BMR). As a consequence, ambient temperature has been considered the
      most important external factor driving the evolution of residual BMR. It is not
      clear, however, whether this relationship is size dependent, and artifacts such
      as the biased sampling of body masses in physiological data sets could cause us
      to overstate the ubiquity of the relationship. Accordingly, here we used
      published data on body mass (mb), BMR, and annual mean temperature (Tmean) for
      458 mammal species (and/or subspecies) to examine the size dependence of the
      relationship between temperature and BMR. We found a significant interaction
      between mb and Tmean as predictors of residual BMR, such that the effect of Tmean
      on residual BMR decreases as a function of mb. In line with this, the amount of
      residual variance in BMR explained by Tmean decreased with increasing mb, from
      20%-30% at body sizes of less than 100 g to almost 0 at body sizes greater than
      1,000 g. These data suggest that our current understanding of the importance of
      broad-scale variation in ambient temperature as a driver of metabolic evolution
      in endotherms probably is affected by the large number of small species in both
      nature and physiological data sets.

PMID- 30205025
TI  - Female Life-History Trade-Offs and the Maintenance of Genetic Variation in
      Drosophila melanogaster.
AB  - Why do we observe substantial variation in fitness-related traits under strong
      natural or sexual selection? While there is support for several selective and
      neutral mechanisms acting in select systems, we lack a comprehensive analysis of
      the relative importance of various mechanisms within a single system.
      Furthermore, while sexually selected male traits have been a central focus of
      this paradox, female sexual traits have rarely been considered. In this study, I
      evaluate the contribution of various selective mechanisms to the maintenance of
      substantial variation in female attractiveness and offspring production observed
      among Drosophila melanogaster genotypes. I tested for contributions from
      antagonistic pleiotropy, frequency-dependent selection, changing environments,
      and sexual conflict. I found negative genetic correlations between some traits
      (male attractiveness vs. female resistance to male harm, early-life offspring
      production vs. reproductive senescence) and genotype-specific changes in fitness
      between environments. However, no measurement found strong trade-offs among the
      fitness components of these genotypes. Overall, I find little evidence that any
      one mechanism is strong enough to maintain genetic variation on its own. Instead,
      I suggest that many mechanisms may weaken the selection among genotypes, which
      would collectively allow neutral processes such as mutation-selection balance to
      maintain genetic variation within populations.

PMID- 30205026
TI  - Prey Limitation Drives Variation in Allometric Scaling of Predator-Prey
      Interactions.
AB  - Ecologists have long searched for a universal size-scaling constant that governs
      trophic interactions. Although this is an appealing theoretical concept, predator
      prey size ratios (PPSRs) vary strikingly across and within natural food webs,
      meaning that predators deviate from their optimal prey size by consuming
      relatively larger or smaller prey. Here we suggest that this unexpected variation
      in allometric scaling of trophic interactions can be predicted by gradients of
      prey limitation consistent with predictions from optimal foraging theory. We
      analyzed >6,000 trophic interactions of 52 populations from four tropical frog
      species along a gradient of prey limitation. The mean of PPSR and its variance
      differed up to two orders of magnitude across and within food webs. Importantly,
      as prey availability decreased across food webs, PPSR and its variance became
      more size dependent. Thus, trophic interactions did not follow a fixed allometric
      scaling but changed predictably with the strength of prey limitation. Our results
      emphasize the importance of ecological contexts in arranging food webs and the
      need to incorporate ecological drivers of PPSR and its variance in food web and
      community models.

PMID- 30205027
TI  - Collective Action Promoted by Key Individuals.
AB  - Explaining why individuals participate in risky group behaviors has been a long
      term challenge. We experimentally studied the formation of groups of birds (mobs)
      that aggressively confront predators and avian nest parasites and developed a
      theoretical model to evaluate the conditions under which mobs arise. We presented
      taxidermied mounts of predators on adult birds (hawks and owls) and of nest
      threats (crows and cuckoos) at different distances to nests of Phylloscopus
      warblers. Even when alone, birds are aggressive toward predators of adult birds,
      both at and away from their nests. By contrast, birds aggressively confront nest
      threats alone only when they have a nest nearby. However, strong initial
      responses by nest owners lead individuals without nearby nests to increase their
      responses, thereby generating a mob. Building on these findings, we derive the
      conditions in which individuals are incentivized to invest more when joining a
      high-gain individual compared to when acting alone. Strong responses of high-gain
      individuals acting alone tend to reduce the investments of other high-gain
      individuals that subsequently join. However, individuals that benefit
      sufficiently little from acting alone increase their investments when joining a
      high-gain individual and can even be sufficiently incentivized to join in when
      they would otherwise not act alone. Together, these results suggest an important
      role for key individuals in the generation of some group behaviors.

PMID- 30205028
TI  - Early and Adult Social Environments Shape Sex-Specific Actuarial Senescence
      Patterns in a Cooperative Breeder.
AB  - Sociality modulates life-history traits through changes in resource allocation to
      fitness-related traits. However, how social factors at different stages of the
      life cycle modulate senescence remains poorly understood. To address this
      question, we assessed the influence of social environment in both early life and
      adulthood on actuarial senescence in the Alpine marmot, a cooperative breeder.
      The influence of helpers on actuarial senescence strongly differed depending on
      when help was provided and on the sex of the dominant. Being helped when adult
      slowed down senescence in both sexes. However, the effect of the presence of
      helpers during the year of birth of a dominant was sex specific. Among dominants
      helped during adulthood, females born in the presence of helpers senesced slower,
      whereas males senesced faster. Among dominants without helpers during adulthood,
      females with helpers at birth senesced faster. Social environment modulates
      senescence but acts differently between sexes and life stages.

PMID- 30205029
TI  - Coevolution Slows the Disassembly of Mutualistic Networks.
AB  - Important groups of mutualistic species are threatened worldwide, and identifying
      factors that make them more or less fragile in the face of disturbance is
      becoming increasingly critical. Although much research has focused on identifying
      the ecological factors that favor the stability of communities rich in
      mutualists, much less has been devoted to understanding the role played by
      historical and contemporary evolution. Here we develop mathematical models and
      computer simulations of coevolving mutualistic communities that allow us to
      explore the importance of coevolution in stabilizing communities against
      anthropogenic disturbance. Our results demonstrate that communities with a long
      history of coevolution are substantially more robust to disturbance, losing
      individual species and interactions at lower rates. In addition, our results
      identify a novel phenomenon-coevolutionary rescue-that mitigates the impacts of
      ongoing anthropogenic disturbance by rewiring the network structure of the
      community in a way that compensates for the extinction of individual species and
      interactions.

PMID- 30205030
TI  - Does Population Structure Predict the Rate of Speciation? A Comparative Test
      across Australia's Most Diverse Vertebrate Radiation.
AB  - Population divergence is the first step in allopatric speciation, as has long
      been recognized in both theoretical models of speciation and empirical
      explorations of natural systems. All else being equal, lineages with substantial
      population differentiation should form new species more quickly than lineages
      that maintain range-wide genetic cohesion through high levels of gene flow.
      However, there have been few direct tests of the extent to which population
      differentiation predicts speciation rates as measured on phylogenetic trees.
      Here, we explicitly test the links between organismal traits, population-level
      processes, and phylogenetic speciation rates across a diverse clade of Australian
      lizards that shows remarkable variation in speciation rate. Using genome-wide
      double digest restriction site-associated DNA data from 892 individuals, we
      generated a comparative data set on isolation by distance and population
      differentiation across 104 putative species-level lineages (operational taxonomic
      units). We find that species show substantial variation in the extent of
      population differentiation, and this variation is predicted by organismal traits
      that are thought to be proxies for dispersal and deme size. However, variation in
      population structure does not predict variation in speciation rate. Our results
      suggest that population differentiation is not the rate-limiting step in species
      formation and that other ecological and historical factors are primary
      determinants of speciation rates at macroevolutionary scales.

PMID- 30205031
TI  - Host Dispersal Responses to Resource Supplementation Determine Pathogen Spread in
      Wildlife Metapopulations.
AB  - Many wildlife species occupy landscapes that vary in the distribution, abundance,
      and quality of food resources. Increasingly, urbanized and agricultural habitats
      provide supplemental food resources that can have profound consequences for host
      distributions, movement patterns, and pathogen exposure. Understanding how host
      and pathogen dispersal across landscapes is affected by the spatial extent of
      food-supplemented habitats is therefore important for predicting the consequences
      for pathogen spread and impacts on host occupancy. Here we develop a
      generalizable metapopulation model to understand how the relative abundance of
      provisioned habitats across the landscape and how the host dispersal responses to
      provisioning and infection influence patch occupancy by hosts and their
      pathogens. We find that pathogen invasion and landscape-level infection
      prevalence are greatest when provisioning increases patch attractiveness and
      disperser production and when infection has minimal costs on dispersal success.
      Alternatively, if provisioning promotes site fidelity or reduces disperser
      production, increasing the fraction of food-supplemented habitats can reduce
      landscape-scale infection prevalence and minimize disease-induced declines in
      host occupancy. This work highlights the importance of considering how resources
      and infection jointly influence host dispersal for predicting how changing
      resource distributions influence the spread of infectious diseases.

PMID- 30205032
TI  - The Energetic Cost of Reproduction and Its Effect on Optimal Life-History
      Strategies.
AB  - Trade-offs in energy allocation between growth, reproduction, and survival are at
      the core of life-history theory. While age-specific mortality is considered to be
      the main determinant of the optimal allocation, some life-history strategies,
      such as delayed or skipped reproduction, may be better understood when also
      accounting for reproduction costs. Here, we present a two-pool indeterminate
      grower model that includes survival and energetic costs of reproduction. The
      energetic cost sets a minimum reserve required for reproduction, while the
      survival cost reflects increased mortality from low postreproductive body
      condition. Three life-history parameters determining age-dependent energy
      allocation to soma, reserve, and reproduction are optimized, and we show that the
      optimal strategies can reproduce realistic emergent growth trajectories,
      maturation ages, and reproductive outputs for fish. The model predicts maturation
      phase shifts along the gradient of condition-related mortality and shows that
      increased harvesting will select for earlier maturation and higher energy
      allocation to reproduction. However, since the energetic reproduction cost sets
      limits on how early an individual can mature, an increase in fitness at high
      harvesting can only be achieved by diverting most reserves into reproduction. The
      model presented here can improve predictions of life-history responses to
      environmental change and human impacts because key life-history traits such as
      maturation age and size, maximum body size, and size-specific fecundity emerge
      dynamically.

PMID- 30205033
TI  - Hyaluronan Works on the Right for Directional Gut Looping.
AB  - The cellular basis of left-right asymmetric organogenesis remains largely
      unknown, but signaling events on the left side were thought to be dominant. In
      this issue of Developmental Cell, however, Sivakumar et al. (2018) suggest that
      covalent modification of hyaluronan on the right side initiates directional
      looping of the developing midgut.

PMID- 30205034
TI  - Pericentrin Knocks Down Cilia in Trisomy 21.
AB  - Down syndrome is a developmental disorder caused by chromosome 21 trisomy,
      whereas ciliopathies result from defective primary cilia. In this issue of
      Developmental Cell, Galati et al. (2018) establish a link between these diseases,
      finding that cilium function is compromised in Down syndrome as a result of
      increased Pericentrin expression.

PMID- 30205035
TI  - A Dilution Model for Embryonic Scaling.
AB  - A recent study in Nature Cell Biology (Almuedo-Castillo et al., 2018) describes a
      mechanism for tissue scaling in zebrafish embryos. The authors show that a fixed
      relative amount of the diffusible Nodal inhibitor Lefty produces an extended
      gradient in larger embryos, ensuring proportionally scaled germ layers,
      irrespective of embryo size.

PMID- 30205036
TI  - Mitochondrial dsRNA: A New DAMP for MDA5.
AB  - The role of mitochondria as a signaling platform downstream of the RNA sensors
      RIG-I and MDA5 is well defined. Now, a recent study in Nature by Dhir et al.
      (2018) identifies mitochondrial dsRNA as an immunogenic ligand, adding another
      intriguing aspect to the role of mitochondria in innate immunity.

PMID- 30205039
TI  - Multiomic Medulloblastomas.
AB  - Epigenomics and transcriptomics of medulloblastoma-an important childhood brain
      tumor-segregate the disease into four clinically relevant subtypes. In this issue
      of Cancer Cell, Archer et al. and Forget et al. add the proteome to our multiomic
      map of this disease, revealing posttranscriptional and posttranslational
      variations with potential therapeutic implications.

PMID- 30205037
TI  - Il34-Csf1r Pathway Regulates the Migration and Colonization of Microglial
      Precursors.
AB  - Microglia are the major immune cells in the central nervous system (CNS). Born in
      peripheral hematopoietic tissues, microglial precursors colonize the CNS during
      early embryogenesis and maintain themselves thereafter. However, the mechanism
      underlying this colonization process remains elusive. We have recently
      demonstrated that neuronal apoptosis contributes to microglia colonization in
      zebrafish. Here, we further show that prior to neuronal apoptosis, microglial
      precursors are attracted to the proximal brain regions by brain-derived
      interleukin 34 (il34) and its receptor colony-stimulating factor 1 receptor a
      (csf1ra). In both il34- and csf1ra-deficient zebrafish larva, embryonic
      macrophages fail to migrate to the anterior head and colonize the CNS, but their
      initial development and colonization to peripheral tissues remain largely
      unaffected. Activation of Il34-Csf1ra pathway is sufficient to attract embryonic
      macrophages to the CNS independent of neuronal apoptosis. Our study shows that
      cytokine signaling and neuronal apoptosis synergistically orchestrate the
      colonization of microglia in early zebrafish development.

PMID- 30205040
TI  - Targeting the Residual Leukemia Cells after Chemotherapy.
AB  - One of the biggest challenges in treating acute myeloid leukemia (AML) is relapse
      of aggressive disease after treatment. In this issue of Cancer Cell, Boyd et al.
      characterize a molecularly distinct population of chemotherapy-induced transient
      leukemic regenerating cells (LRCs), which can be exploited to prevent AML
      recurrence.

PMID- 30205041
TI  - Location, Location, Location: Mutant NPM1c Cytoplasmic Localization Is Required
      to Maintain Stem Cell Genes in AML.
AB  - In this issue of Cancer Cell, Brunetti and colleagues elucidate the role of
      mutant NPM1c and its cytoplasmic mislocalization in acute myeloid leukemia. They
      demonstrate how mutant-specific degradation or relocalization leads to a loss of
      the stem cell signature characteristic of these leukemias and induces their
      differentiation.

PMID- 30205038
TI  - WDR5 Stabilizes Actin Architecture to Promote Multiciliated Cell Formation.
AB  - The actin cytoskeleton is critical to shape cells and pattern intracellular
      organelles, which collectively drives tissue morphogenesis. In multiciliated
      cells (MCCs), apical actin drives expansion of the cell surface necessary to host
      hundreds of cilia. The apical actin also forms a lattice to uniformly distribute
      basal bodies. This apical actin network is dynamically remodeled, but the
      molecules that regulate its architecture remain poorly understood. We identify
      the chromatin modifier, WDR5, as a regulator of apical F-actin in MCCs.
      Unexpectedly in MCCs, WDR5 has a function independent of chromatin modification.
      We discover a scaffolding role for WDR5 between the basal body and F-actin.
      Specifically, WDR5 binds to basal bodies and migrates apically, where F-actin
      organizes around WDR5. Using a monomer trap for G-actin, we show that WDR5
      stabilizes F-actin to maintain lattice architecture. In summary, we identify a
      non-chromatin role for WDR5 in stabilizing F-actin in MCCs.

PMID- 30205042
TI  - GABPbeta1L Wakes Up TERT.
AB  - TERT catalyzes telomere maintenance. While silenced in most normal somatic cells,
      TERT is expressed in cancer, often due to promoter mutations, facilitating
      replicative immortality. In this issue of Cancer Cell, Mancini et al. demonstrate
      that GABPbeta1L is required for mutant TERT promoter activity, thus identifying a
      potential therapeutic target.

PMID- 30205044
TI  - Proteomics, Post-translational Modifications, and Integrative Analyses Reveal
      Molecular Heterogeneity within Medulloblastoma Subgroups.
AB  - There is a pressing need to identify therapeutic targets in tumors with low
      mutation rates such as the malignant pediatric brain tumor medulloblastoma. To
      address this challenge, we quantitatively profiled global proteomes and phospho
      proteomes of 45 medulloblastoma samples. Integrated analyses revealed that tumors
      with similar RNA expression vary extensively at the post-transcriptional and post
      translational levels. We identified distinct pathways associated with two subsets
      of SHH tumors, and found post-translational modifications of MYC that are
      associated with poor outcomes in group 3 tumors. We found kinases associated with
      subtypes and showed that inhibiting PRKDC sensitizes MYC-driven cells to
      radiation. Our study shows that proteomics enables a more comprehensive,
      functional readout, providing a foundation for future therapeutic strategies.

PMID- 30205043
TI  - Aberrant ERBB4-SRC Signaling as a Hallmark of Group 4 Medulloblastoma Revealed by
      Integrative Phosphoproteomic Profiling.
AB  - The current consensus recognizes four main medulloblastoma subgroups (wingless,
      Sonic hedgehog, group 3 and group 4). While medulloblastoma subgroups have been
      characterized extensively at the (epi-)genomic and transcriptomic levels, the
      proteome and phosphoproteome landscape remain to be comprehensively elucidated.
      Using quantitative (phospho)-proteomics in primary human medulloblastomas, we
      unravel distinct posttranscriptional regulation leading to highly divergent
      oncogenic signaling and kinase activity profiles in groups 3 and 4
      medulloblastomas. Specifically, proteomic and phosphoproteomic analyses identify
      aberrant ERBB4-SRC signaling in group 4. Hence, enforced expression of an
      activated SRC combined with p53 inactivation induces murine tumors that resemble
      group 4 medulloblastoma. Therefore, our integrative proteogenomics approach
      unveils an oncogenic pathway and potential therapeutic vulnerability in the most
      common medulloblastoma subgroup.

PMID- 30205046
TI  - Overcoming Resistance to Dual Innate Immune and MEK Inhibition Downstream of
      KRAS.
AB  - Despite extensive efforts, oncogenic KRAS remains resistant to targeted therapy.
      Combined downstream RAL-TBK1 and MEK inhibition induces only transient lung tumor
      shrinkage in KRAS-driven genetically engineered mouse models (GEMMs). Using the
      sensitive KRAS;LKB1 (KL) mutant background, we identify YAP1 upregulation and a
      therapy-induced secretome as mediators of acquired resistance. This program is
      reversible, associated with H3K27 promoter acetylation, and suppressed by BET
      inhibition, resensitizing resistant KL cells to TBK1/MEK inhibition. Constitutive
      YAP1 signaling promotes intrinsic resistance in KRAS;TP53 (KP) mutant lung
      cancer. Intermittent treatment with the BET inhibitor JQ1 thus overcomes
      resistance to combined pathway inhibition in KL and KP GEMMs. Using potent and
      selective TBK1 and BET inhibitors we further develop an effective therapeutic
      strategy with potential translatability to the clinic.

PMID- 30205045
TI  - The Genomic Landscape of Endocrine-Resistant Advanced Breast Cancers.
AB  - We integrated the genomic sequencing of 1,918 breast cancers, including 1,501
      hormone receptor-positive tumors, with detailed clinical information and
      treatment outcomes. In 692 tumors previously exposed to hormonal therapy, we
      identified an increased number of alterations in genes involved in the mitogen
      activated protein kinase (MAPK) pathway and in the estrogen receptor
      transcriptional machinery. Activating ERBB2 mutations and NF1 loss-of-function
      mutations were more than twice as common in endocrine resistant tumors.
      Alterations in other MAPK pathway genes (EGFR, KRAS, among others) and estrogen
      receptor transcriptional regulators (MYC, CTCF, FOXA1, and TBX3) were also
      enriched. Altogether, these alterations were present in 22% of tumors, mutually
      exclusive with ESR1 mutations, and associated with a shorter duration of response
      to subsequent hormonal therapies.

PMID- 30205047
TI  - MEF2B Instructs Germinal Center Development and Acts as an Oncogene in B Cell
      Lymphomagenesis.
AB  - The gene encoding the MEF2B transcription factor is mutated in germinal center
      (GC)-derived B cell lymphomas, but its role in GC development and lymphomagenesis
      is unknown. We demonstrate that Mef2b deletion reduces GC formation in mice and
      identify MEF2B transcriptional targets in GC, with roles in cell proliferation,
      apoptosis, GC confinement, and differentiation. The most common lymphoma
      associated MEF2B mutant (MEF2BD83V) is hypomorphic, yet escapes binding and
      negative regulation by components of the HUCA complex and class IIa HDACs.
      Mef2bD83V expression in mice leads to GC enlargement and lymphoma development, a
      phenotype that becomes fully penetrant in combination with BCL2 de-regulation, an
      event associated with human MEF2B mutations. These results identify MEF2B as a
      critical GC regulator and a driver oncogene in lymphomagenesis.

PMID- 30205048
TI  - Identification of Chemotherapy-Induced Leukemic-Regenerating Cells Reveals a
      Transient Vulnerability of Human AML Recurrence.
AB  - Despite successful remission induction, recurrence of acute myeloid leukemia
      (AML) remains a clinical obstacle thought to be caused by the retention of
      dormant leukemic stem cells (LSCs). Using chemotherapy-treated AML xenografts and
      patient samples, we have modeled patient remission and relapse kinetics to reveal
      that LSCs are effectively depleted via cell-cycle recruitment, leaving the
      origins of relapse unclear. Post-chemotherapy, in vivo characterization at the
      onset of disease relapse revealed a unique molecular state of leukemic
      regenerating cells (LRCs) responsible for disease re-growth. LRCs are transient,
      can only be detected in vivo, and are molecularly distinct from therapy-naive
      LSCs. We demonstrate that LRC features can be used as markers of relapse and are
      therapeutically targetable to prevent disease recurrence.

PMID- 30205051
TI  - Individual variation in human navigation.
AB  - The cognitive map view of navigation posits that humans and other species
      represent space in a format that encodes the distances and directions among
      locations in relation to external reference frames such as boundaries and
      landmarks. Such an allocentric representation is combined with egocentric
      representations that track a navigator's position over movement. Jointly, these
      systems enable the flexible planning of routes, including shortcuts, detours, and
      paths between two locations not formerly travelled. Tolman's (1948) work on the
      sunburst maze initiated this tradition. In the sunburst maze, rats who had
      followed a circuitous route to find a reward, as shown at the left of Figure 1,
      could take a shortcut to the goal when their route was blocked and other routes
      were offered, as shown at the right of Figure 1. That is, to use one set of
      terms, they were place learners as well as response learners, or to use another
      set of terms, they formed survey representations as well as route
      representations.

PMID- 30205052
TI  - Demystifying Monarch Butterfly Migration.
AB  - Every fall, millions of North American monarch butterflies undergo a stunning
      long-distance migration to reach their overwintering grounds in Mexico. Migration
      allows the butterflies to escape freezing temperatures and dying host plants, and
      reduces infections with a virulent parasite. We discuss the multigenerational
      migration journey and its evolutionary history, and highlight the navigational
      mechanisms of migratory monarchs. Monarchs use a bidirectional time-compensated
      sun compass for orientation, which is based on a time-compensating circadian
      clock that resides in the antennae, and which has a distinctive molecular
      mechanism. Migrants can also use a light-dependent inclination magnetic compass
      for orientation under overcast conditions. Additional environmental features,
      e.g., atmospheric conditions, geologic barriers, and social interactions, likely
      augment navigation. The publication of the monarch genome and the development of
      gene-editing strategies have enabled the dissection of the genetic and
      neurobiological basis of the migration. The monarch butterfly has emerged as an
      excellent system to study the ecological, neural, and genetic basis of long
      distance animal migration.

PMID- 30205049
TI  - Mutant NPM1 Maintains the Leukemic State through HOX Expression.
AB  - NPM1 is the most frequently mutated gene in cytogenetically normal acute myeloid
      leukemia (AML). In AML cells, NPM1 mutations result in abnormal cytoplasmic
      localization of the mutant protein (NPM1c); however, it is unknown whether NPM1c
      is required to maintain the leukemic state. Here, we show that loss of NPM1c from
      the cytoplasm, either through nuclear relocalization or targeted degradation,
      results in immediate downregulation of homeobox (HOX) genes followed by
      differentiation. Finally, we show that XPO1 inhibition relocalizes NPM1c to the
      nucleus, promotes differentiation of AML cells, and prolongs survival of Npm1
      mutated leukemic mice. We describe an exquisite dependency of NPM1-mutant AML
      cells on NPM1c, providing the rationale for the use of nuclear export inhibitors
      in AML with mutated NPM1.

PMID- 30205053
TI  - The Neurobiology of Mammalian Navigation.
AB  - Mammals have evolved specialized brain systems to support efficient navigation
      within diverse habitats and over varied distances, but while navigational
      strategies and sensory mechanisms vary across species, core spatial components
      appear to be widely shared. This review presents common elements found in
      mammalian spatial mapping systems, focusing on the cells in the hippocampal
      formation representing orientational and locational spatial information, and
      'core' mammalian hippocampal circuitry. Mammalian spatial mapping systems make
      use of both allothetic cues (space-defining cues in the external environment) and
      idiothetic cues (cues derived from self-motion). As examples of each cue type, we
      discuss: environmental boundaries, which control both orientational and
      locational neuronal activity and behaviour; and 'path integration', a process
      that allows the estimation of linear translation from velocity signals, thought
      to depend upon grid cells in the entorhinal cortex. Building cognitive maps
      entails sampling environments: we consider how the mapping system controls
      exploration to acquire spatial information, and how exploratory strategies may
      integrate idiothetic with allothetic information. We discuss how 'replay' may act
      to consolidate spatial maps, and simulate trajectories to aid navigational
      planning. Finally, we discuss grid cell models of vector navigation.

PMID- 30205054
TI  - Principles of Insect Path Integration.
AB  - Continuously monitoring its position in space relative to a goal is one of the
      most essential tasks for an animal that moves through its environment. Species as
      diverse as rats, bees, and crabs achieve this by integrating all changes of
      direction with the distance covered during their foraging trips, a process called
      path integration. They generate an estimate of their current position relative to
      a starting point, enabling a straight-line return, following what is known as a
      home vector. While in theory path integration always leads the animal precisely
      back home, in the real world noise limits the usefulness of this strategy when
      operating in isolation. Noise results from stochastic processes in the nervous
      system and from unreliable sensory information, particularly when obtaining
      heading estimates. Path integration, during which angular self-motion provides
      the sole input for encoding heading (idiothetic path integration), results in
      accumulating errors that render this strategy useless over long distances. In
      contrast, when using an external compass this limitation is avoided (allothetic
      path integration). Many navigating insects indeed rely on external compass cues
      for estimating body orientation, whereas they obtain distance information by
      integration of steps or optic-flow-based speed signals. In the insect brain, a
      region called the central complex plays a key role for path integration. Not only
      does the central complex house a ring-attractor network that encodes head
      directions, neurons responding to optic flow also converge with this circuit. A
      neural substrate for integrating direction and distance into a memorized home
      vector has therefore been proposed in the central complex. We discuss how
      behavioral data and the theoretical framework of path integration can be aligned
      with these neural data.

PMID- 30205050
TI  - Disruption of the beta1L Isoform of GABP Reverses Glioblastoma Replicative
      Immortality in a TERT Promoter Mutation-Dependent Manner.
AB  - TERT promoter mutations reactivate telomerase, allowing for indefinite telomere
      maintenance and enabling cellular immortalization. These mutations specifically
      recruit the multimeric ETS factor GABP, which can form two functionally
      independent transcription factor species: a dimer or a tetramer. We show that
      genetic disruption of GABPbeta1L (beta1L), a tetramer-forming isoform of GABP
      that is dispensable for normal development, results in TERT silencing in a TERT
      promoter mutation-dependent manner. Reducing TERT expression by disrupting beta1L
      culminates in telomere loss and cell death exclusively in TERT promoter mutant
      cells. Orthotopic xenografting of beta1L-reduced, TERT promoter mutant
      glioblastoma cells rendered lower tumor burden and longer overall survival in
      mice. These results highlight the critical role of GABPbeta1L in enabling
      immortality in TERT promoter mutant glioblastoma.

PMID- 30205056
TI  - The mouse as a model for neuropsychiatric drug development.
AB  - Much has been written about the validity of mice as a preclinical model for brain
      disorders. Critics cite numerous examples of apparently effective treatments in
      mouse models that failed in human clinical trials, raising the possibility that
      the two species' neurobiological differences could explain the high translational
      failure rate in psychiatry and neurology (neuropsychiatry). However, every stage
      of translation is plagued by complex problems unrelated to neurobiological
      conservation. Therefore, although these case studies are intriguing, they cannot
      alone determine whether these differences observed account for translation
      failures. Our analysis of the literature indicates that most neuropsychiatric
      treatments used in humans are at least partially effective in mouse models,
      suggesting that neurobiological differences are unlikely to be the main cause of
      neuropsychiatric translation failures.

PMID- 30205057
TI  - Capsella.
AB  - Capsella species, including the well-known Shephard's purse, are characterized by
      small white flowers and heart-shaped fruit. But read on to discover the
      fascinating insights these diminutive plants have to reveal about the evolution
      of self-fertilizing plants.

PMID- 30205058
TI  - The exocyst complex.
AB  - The exocyst is a multisubunit protein complex that was first identified and
      characterized in budding yeast. Later studies have demonstrated its conservation
      in eukaryotes, from plants to mammals. This complex mediates the tethering of
      secretory vesicles to the plasma membrane prior to fusion mediated by soluble N
      ethylmaleimide-sensitive factor attachment protein receptors (SNAREs). The
      exocyst has been implicated in a variety of cellular processes, such as
      exocytosis, cell growth, cytokinesis, cell migration, primary ciliogenesis and
      tumorigenesis. Recent years have seen major progress in our understanding of this
      complex. In this Primer, we focus on some of the basic information about the
      exocyst complex, including its structure, assembly, molecular interactions,
      function in vesicle tethering and membrane fusion, and involvement in many
      physiological processes.

PMID- 30205060
TI  - High-frequency vocalizations in Andean hummingbirds.
AB  - Hummingbirds possess a number of unique features. A recent report in Current
      Biology[1] showed that the Black Jacobin (Florisuga fusca), a Brazilian
      hummingbird in the Topazes clade, produces high-frequency vocalizations outside
      the known hearing range of birds. Here, we report that four hummingbird species
      in the Andean clade [2,3] also exhibit high-frequency vocalizations: the
      Ecuadorian Hillstar (Oreotrochilus chimborazo), with the highest fundamental
      frequency (mean F0 = 13.4 kHz), the Buff-tailed Coronet (Boissonneaua
      flavescens), Speckled Hummingbird (Adelomyia melanogenys) and Violet-tailed Sylph
      (Aglaiocercus coelestis). The presence of high-frequency vocalizations in
      hummingbirds belonging to different lineages poses the question of whether high
      frequency vocalizations in this group of birds have been, so far, overlooked.
      These Andean species are closely related but live in two different habitats. Our
      characterization of ambient noise in each habitat suggests that the hummingbirds
      are exposed to different acoustic challenges, and that the frequency content of
      the vocalizations of the cloud-forest species is adapted accordingly. The
      function of these signals and the selection pressures driving their evolution
      remain unknown.

PMID- 30205059
TI  - Visual asymmetries in cuttlefish during brightness matching for camouflage.
AB  - Many animals use camouflage to avoid detection by predators. Camouflage can take
      several forms, one of which includes brightness matching, a form of crypsis,
      which occurs when an individual resembles the brightness of their surrounding
      habitat. Most animals have evolved skin patterning that is fixed and specific to
      their environment, typically limiting their camouflage abilities to a particular
      habitat [1]. By contrast, crypsis in cuttlefish is dynamic because they can
      change their body patterns rapidly (270-730 milliseconds) in response to the
      visual environment through neural control of pigmented organs known as
      chromatophores [2,3]. Cuttlefish respond to conflicting visual cues, that is, to
      different visual information on their left and right sides, with mixed body
      patterns [4]. This response may be modulated by perceptual asymmetries in visual
      processing, since cuttlefish exhibit biases when processing visual information,
      termed visual lateralization [5]. Visual lateralization occurs when information
      in one visual field is prioritized over the other visual field during a specific
      behavior, but this phenomenon and its potential effect on camouflage behavior
      have never before been investigated. We report here that juvenile cuttlefish have
      a right eye preference for brightness matching, as the substrate perceived in
      their right visual field was prioritized.

PMID- 30205061
TI  - Bub1 is not essential for the checkpoint response to unattached kinetochores in
      diploid human cells.
AB  - Error-free chromosome segregation during mitosis depends on a functional spindle
      assembly checkpoint (SAC). The SAC is a multi-component signalling system that is
      recruited to unattached or incorrectly attached kinetochores to catalyse the
      formation of a soluble inhibitor, known as the Mitotic Checkpoint Complex (MCC),
      which binds and inhibits the anaphase promoting complex (APC/C) [1]. We have
      previously proposed that two separable pathways, composed of KNL1-Bub3-Bub1 (KBB)
      and Rod-Zwilch-Zw10 (RZZ), recruit Mad1-Mad2 complexes to human kinetochores to
      activate the SAC [2]. Although Bub1 is absolutely required for checkpoint
      signalling in yeast (which lack RZZ), there is conflicting evidence as to whether
      this is the case in human cells based on siRNA studies [2-5]. Here we show that,
      while Bub1 is required for recruitment of BubR1, it is not strictly required for
      the checkpoint response to unattached kinetochores in diploid human cells.

PMID- 30205062
TI  - Plant Biology: The Making of an Epithelium.
AB  - The endodermis of plants is surrounded by an impermeable belt, the casparian
      strip, making it a highly selective barrier for nutrient uptake. Successful
      reprogramming of non-endodermal cells to form a casparian strip requires two
      signals produced by the vasculature.

PMID- 30205055
TI  - The Neurocognitive Basis of Spatial Reorientation.
AB  - The ability to recover one's bearings when lost is a skill that is fundamental
      for spatial navigation. We review the cognitive and neural mechanisms that
      underlie this ability, with the aim of linking together previously disparate
      findings from animal behavior, human psychology, electrophysiology, and cognitive
      neuroscience. Behavioral work suggests that reorientation involves two key
      abilities: first, the recovery of a spatial reference frame (a cognitive map)
      that is appropriate to the current environment; and second, the determination of
      one's heading and location relative to that reference frame. Electrophysiological
      recording studies, primarily in rodents, have revealed potential correlates of
      these operations in place, grid, border/boundary, and head-direction cells in the
      hippocampal formation. Cognitive neuroscience studies, primarily in humans,
      suggest that the perceptual inputs necessary for these operations are processed
      by neocortical regions such as the retrosplenial complex, occipital place area
      and parahippocampal place area, with the retrosplenial complex mediating spatial
      transformations between the local environment and the recovered spatial reference
      frame, the occipital place area supporting perception of local boundaries, and
      the parahippocampal place area processing visual information that is essential
      for identification of the local spatial context. By combining results across
      these various literatures, we converge on a unified account of reorientation that
      bridges the cognitive and neural domains.

PMID- 30205063
TI  - Insect Orientation: Stay on Course with the Sun.
AB  - A new study demonstrates that fruit flies can use a sun compass, which is encoded
      in specific neurons in the fly's brain, to maintain a fixed heading direction for
      up to six hours.

PMID- 30205064
TI  - Attention: Noisy Networks Are Tuned Out by the Claustrum.
AB  - The claustrum is one of the most well connected regions of the brain, yet its
      function has remained a mystery. A new study involving selective suppression of
      the activity of claustrum neurons has provided insight into the role of the
      claustrum in mediating attention.

PMID- 30205065
TI  - cGMP Signalling: Malarial Guanylyl Cyclase Leads the Way.
AB  - When ingested by a mosquito, the malaria parasite relies on an unusual form of
      gliding motility to escape from the rapidly deteriorating blood meal. A new study
      on an atypical malaria guanylyl cyclase reveals the importance of spatiotemporal
      regulation of cGMP production in this process.

PMID- 30205066
TI  - Evolution: New Branches on the Alvarezsaur Tree.
AB  - Two new species of dinosaur from the mid-Cretaceous of China document previously
      unknown stages in the evolutionary transition from primitive Jurassic carnivores
      to the highly transformed insectivorous alvarezsaurids of the Late Cretaceous.

PMID- 30205067
TI  - Cell Division: Here Comes the Kinesin Cavalry.
AB  - A new study finds that a spindle motor makes an unexpected contribution to
      kinetochore-microtubule attachments and chromosome segregation.

PMID- 30205068
TI  - Reproductive Strategies: Eat Your Kids to Restart Your Sex Life.
AB  - A recent study shows that filial cannibalism is not merely a desperate survival
      tactic for hungry fathers. Rather, brood destruction triggers sexual physiology,
      enabling males to restart courtship with new partners. Like abandonment and
      infanticide by males and females across taxa, cannibalism generates evolutionary
      conflict between fathers, mothers, and offspring.

PMID- 30205069
TI  - Spindle Assembly: Two Spindles for Two Genomes in a Mammalian Zygote.
AB  - A single bipolar spindle was thought to form around both parental genomes in
      zygotes initiating the first division. A recent study challenges this predominant
      view by showing that two independent spindles assemble to prevent parental genome
      mixing in mouse zygotes.

PMID- 30205070
TI  - Animal migration research takes wing.
AB  - In the beginning there was great confusion about animal migration. Aristotle,
      noting that the types of birds around him changed with the seasons, concluded
      that summer redstarts turned into robins at the onset of winter, and that garden
      warblers became blackcaps [1]. Others thought that birds disappear in winter
      because they hibernate submerged in mud. In a case of art decidedly not imitating
      life, a 16th century illustration accompanying the writings of Swedish Archbishop
      Olaus Magnus showed a fishing net filled with hibernating swallows being pulled
      from a lake [1]. Gradually, over centuries, these fanciful early explanations
      gave way to an understanding that migration is a widespread phenomenon and that
      Earth is alive with itinerant animals traversing continents, seas, and skies
      (Figure 1).

PMID- 30205071
TI  - Homing pigeons.
AB  - Dora Biro introduces homing domestic pigeons specialized for messaging duties.

PMID- 30205072
TI  - Ecology of animal migration.
AB  - Billions of animals are adapted to a travelling life, making regular return
      migrations between more or less distant living stations on Earth by swimming,
      flying, running or walking (Figure 1). Extremely long migrations are completed
      annually by whales between calving areas in warmer waters and feeding areas at
      higher latitudes in either hemisphere. The longest oceanic migrations among sea
      turtles and fish are often undertaken by younger immature individuals during a
      period of several years before they start their more regular return visits to
      breeding and spawning sites. Among adult leatherback turtles, intervals of
      several years between successive breeding events leave enough time for extremely
      long journeys. Famous among bird migrants are arctic terns, showing the longest
      known annual migration circuit of about 50,000 km. Bar-tailed godwits breed in
      Alaska and winter in New Zealand and make the longest known non-stop flapping
      flights, lasting more than two hundred hours and covering up to 12,000 km across
      the Pacific Ocean. Their total annual migration circuit extends over 30,000 km
      covered in three main flights (Figure 1). Although diapause with hibernation as
      egg, pupae, larvae or adult is an important strategy among insects, there are
      also examples of impressive migrations. Monarch butterflies complete an annual
      circuit up to 9,000 km in North America in four generations (for more detail, see
      the review by Steven Reppert in this issue), and the globe skimmer (a dragonfly)
      presumably exploits the monsoon rains in India and rainy seasons in southern and
      equatorial Africa in a 15,000 km circuit in four generations (Figure 1). In
      comparison with swimmers and flyers, animals that migrate by running or walking
      cover shorter distances. Caribous migrate between boreal forest and tundra over a
      total distance of not much more than 1000-2000 km per year. Zebras make the
      longest migrations in Africa, covering at least 500 km, which is just a little
      bit longer than the well-known wildebeest migration circuit in Serengeti.

PMID- 30205073
TI  - Marine migrations.
AB  - There is great diversity in the animal species that migrate, the biomechanics
      that propel their locomotion and the ecosystems through which they transit. This
      diversity, however, is unified by a common condition: the relative suitability of
      places changes in predictable and cyclical ways. Owing to the periodicity of
      environmental change (e.g., seasons) and animal life-cycles (e.g., growth and
      maturation) locations become favorable, lose favorability and become favorable
      again at somewhat regular intervals. Migratory animals have adapted to these
      predictable fluctuations by moving among locations, sometimes over extraordinary
      distances (Figure 1).

PMID- 30205074
TI  - Collective animal migration.
AB  - Migratory movement is a strategy employed by a broad range of taxa as a response
      to temporally and spatially varying environmental conditions. Multiple factors
      can drive animal migration, including movement to hospitable environments when
      local conditions become unfavourable (such as to reduce nutritional and
      thermoregulatory stress), movement to find mates and/or breeding sites, and
      movement to minimise competition, predation, infection or parasitism. Migrating
      animals can often be seen to move together (Figure 1), sometimes in vast numbers.
      Despite this, the social aspects of migration have, to date, received very
      limited attention. Synchronisation of migratory behaviour among organisms,
      itself, does not imply that migrants utilise social information: synchrony is
      inevitable if there are relatively short windows of opportunity in which to move,
      or there exist sudden environmental changes that must be responded to. However,
      as will be outlined here, there is there is growing evidence that many migratory
      animals do utilise social cues, and that collective factors could shape migration
      in a variety of important ways.

PMID- 30205075
TI  - Conservation of migratory species.
AB  - Were you to find yourself somehow transported to the American Midwest in the 18th
      century, one feature that might strike you would be a curiously shifting cloud
      approaching from the northeast. As it drew closer, you might begin to discern
      some sound, "[like] an army of horses laden with sleigh bells" in the words of a
      Potawatomi Native American. However, not until it was nearly upon you would it
      become apparent that this cloud was made up of billions of individual birds. This
      was the autumn migration of the passenger pigeon (Ectopistes migratorius), the
      most abundant bird to ever be found in North America and perhaps in the world
      (Figure 1). By some estimates, the number of passenger pigeons in North America
      at the time of European colonization was greater than the combined number of all
      birds of all species found on the continent today. Yet, by the beginning of the
      20th century, passenger pigeons had effectively been eradicated, in large part
      due to the extraordinary keenness with which they were hunted. By 1914, 5 billion
      birds were gone and the last passenger pigeon, Martha, died in the Cincinnati
      Zoo. Passenger pigeons represented an extraordinary example of one of Earth's
      great natural phenomena: the annual migration of organisms. They also highlight
      the potential vulnerability of migratory species. These seasonal movements are
      not only awe-inspiring; they are also critical for the health of countless
      species and ecosystems.

PMID- 30205076
TI  - Insect learning flights and walks.
AB  - Knowledge of where things are in one's habitual surroundings cannot be encoded
      genetically and must be acquired in those surroundings. Many ants, bees and wasps
      forage from a home base and before doing so learn where resources are to be found
      and how to return with them to their nest. A significant component of this
      navigational learning seems to be the acquisition of panoramic views that insects
      record close to their nests and resource sites and along the paths between these
      places. Behavioural evidence indicates that these views are retinotopic, meaning,
      for instance, that an insect knows that it faces along a familiar route, if the
      image on its retina matches a view that it had previously recorded, when facing
      in that direction during route learning.

PMID- 30205077
TI  - Neuroethology of spatial cognition.
AB  - A key challenge for animals is recognising locations and navigating between them.
      These capacities are varied: we can remember where our car is parked at the mall,
      rats are able to remember where their nest location is while foraging for food
      morsels, and bats are able to fly directly to a favourite fruit tree 20
      kilometers from their home cave. These spatial abilities, whether commonplace or
      remarkable, raise fundamental questions. First, how do animals find their way?
      Second, how does the brain represent the outside world? In this Primer, we will
      address both questions from the perspective of rodent cognition and neuroscience.

PMID- 30205078
TI  - The Dung Beetle Compass.
AB  - What do a burly rower, a backstroke swimmer and a hard-working South African dung
      beetle all have in common? The answer is: they all benefit from moving along a
      straight path, and do so moving backwards. This, however, is where the similarity
      ends. While the rower has solved this navigational challenge by handing the task
      of steering to the coxswain, who faces the direction of travel, and the swimmer
      is guided down her lane by colourful ropes, the beetle puts its faith in the sky.
      From here, it utilises a larger repertoire of celestial compass cues than is
      known to be used by any other animal studied to date. A robust internal compass,
      designed to interpret directional information, has evolved under the selective
      pressure of shifting today's lunch efficiently out of reach of competitors, also
      drawn to the common buffet. While this is a goal that beetles might share with
      the hungry athletes, they reach it with drastically different brain powers; the
      brain of the beetle is several times smaller than a match head, containing fewer
      than a million neurons.

PMID- 30205079
TI  - Neuroethology of bat navigation.
AB  - Once a year about 15 million Mexican free-tailed bats (Tadarida brasiliensis)
      migrate up to 1,500 kilometers from wintering grounds, seamlessly flying over the
      Mexican border to enter the United States. Their destination is the Bracken Cave
      in southern Texas, which will be their summer home between the months of March
      through October. While residing there, these bats emerge every night at dusk from
      the narrow 100-foot-wide opening of this enormous cave and begin their nightly
      commute to foraging grounds located up to 50 kilometers away. Upon arrival, they
      will spend the night hunting for insects in mid-air while providing a valuable
      service to local farmers by keeping crop pests in check. Close to the break of
      dawn, as the night of hunting comes to an end, these bats will begin making their
      trip back to the roost.

PMID- 30205080
TI  - Progenitor targeting by adult stem cells in Ciona homeostasis, injury, and
      regeneration.
AB  - In the ascidian Ciona intestinalis, oral siphon amputation activates adult stem
      cell niches in the branchial sac to divide and dispatch migratory progenitor
      cells to a regeneration blastema at the site of injury. This study shows that
      progenitor cells derived from branchial sac stem cell niches have roles in
      homeostasis, wound repair, and regeneration of the siphons and neural complex
      (NC). During homeostasis, progenitor cells targeted the pharyngeal stigmata to
      replace ciliated cells involved in filter feeding. After individual or double
      siphon amputations, progenitor cells specifically targeted the oral or atrial
      siphons or both siphons, and were involved in the replacement of siphon circular
      muscle fibers. After oral siphon wounding, progenitor cells targeted the wound
      sites, and in some cases a supernumerary siphon was formed, although progenitor
      cell targeting did not predict the induction of supernumerary siphons. Following
      NC ablation, progenitor cells specifically targeted the regenerating NC, and
      supplied the precursors of new brain and neural gland cells. The tissues and
      organs targeted by branchial sac stem cells exhibited apoptosis during
      homeostasis and injury. It is concluded that branchial sac progenitor cells are
      multipotent and show targeting specificity that is correlated with apoptosis
      during homeostatic growth, tissue repair, and regeneration.

PMID- 30205081
TI  - 2,4-Diamino-N10-methylpteroic acid (DAMPA) crystalluria in a patient with
      osteosarcoma treated with carboxypeptidase-G2 rescue after high-dose methotrexate
      induced nephrotoxicity.
AB  - BACKGROUND: High-dose methotrexate (HDMTX) therapy is a key component of many
      chemotherapy protocols. However, some patients develop HDMTX-induced
      nephrotoxicity. Carboxypeptidase-G2 (CPDG2) hydrolyses MTX into 2,4-diamino-N10
      methylpteroic acid (DAMPA) and glutamic acid, and is used as a rescue agent in
      patients with nephrotoxicity and delayed elimination. Despite the frequency of
      HDMTX-induced renal injury, crystalluria is uncommon. Furthermore, crystals are
      rarely identified by conventional chemical methods. OBJECTIVE: To determine the
      composition of crystalluria in a patient with osteosarcoma who was treated with
      CPDG2. METHODS: Crystalluria was evaluated by optical microscopy, and chemical
      identification was performed by Fourier-transform infrared (FT-IR) spectroscopy,
      scanning electron microscopy (SEM) and OrbitrapTM high-resolution mass
      spectrometry (HRMS). RESULTS: The HRMS spectra of the patient's urine sediment
      showed a main peak at m/z 326.13, corresponding to the molecular mass of DAMPA
      [(C15H15O2N7) + H+]. The FT-IR spectral patterns of the sediment and DAMPA were
      not identical. SEM was unable to identify the crystal. CONCLUSION: DAMPA
      crystalluria was identified by OrbitrapTM HRMS in a patient treated with CPDG2
      after HDMTX nephrotoxicity. This case reinforces the need to implement adequate
      measures to prevent nephrotoxicity. In cases of HDMTX-induced nephrotoxicity,
      urine sediment analysis should be requested.

PMID- 30205082
TI  - Parasitic interactions among Trypanosoma cruzi, triatomine vectors, domestic
      animals, and wildlife in Big Bend National Park along the Texas-Mexico border.
AB  - National parks attract millions of visitors each year. Park visitors, employees,
      and pets are at risk of infection with various zoonotic pathogens, including
      Trypanosoma cruzi, causative agent of Chagas disease. Big Bend National Park is
      located along the Texas-Mexico border in a region with endemic triatomine insects
      vectors of T. cruzi- yet the degree to which the parasite is transmitted in this
      region is unknown. We collected triatomines for T. cruzi detection and discrete
      typing unit (DTU) determination, and conducted blood meal analyses to determine
      recent hosts. As an index of domestic/peridomestic transmission, we tested
      residential dogs in the Park for exposure to T. cruzi. From 2015 to 2017, 461
      triatomines of three species-Triatoma rubida, Triatoma gerstaeckeri, and Triatoma
      protracta-were collected in and around the Park. Adult triatomine encounters
      peaked in June of each year (52.8% of collections). We detected an overall
      infection prevalence of 23.1% in adult triatomines (n = 320) and 4.2% in nymph
      triatomines (n = 24). DTU TcI was the only T. cruzi strain detected. Of 89
      triatomines subjected to blood meal analyses, vertebrate host DNA was
      successfully amplified from 42 (47.2%); blood meal sources included humans,
      domestic animals, and avian and mammalian wildlife species. Tested dogs were
      considered positive if reactive on at least two independent serologic assays; we
      found 28.6% seroprevalence in 14 dogs. These findings reveal interactions between
      infected triatomines, humans, dogs, and wildlife in and around Big Bend National
      Park, with potential risk of human disease.

PMID- 30205083
TI  - The Association Of Performance Status And Disease Severity In Patients With
      Chronic Graft-Versus-Host Disease.
AB  - OBJECTIVE: Determine the relationship between functional status and degree of
      specific organ involvement, physical performance, and subjective well-being
      Chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic stem
      cell transplantation DESIGN: Observational cohort. SETTING: Outpatient clinic.
      PARTICIPANTS: Adult patients (N = 121) with cGVHD with 634 assessments.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE(S): Karnofsky Performance
      Status (KPS). Skin, fascia/joints, lungs, upper and lower extremity range of
      motion, liver, eye, mucosal, and gastrointestinal involvement were measured using
      the National Institutes of Health GVHD scale. Physical performance was assessed
      with the 2-Minute Walk test and hand grip strength. Subjective measures were the
      Patient Health Questionnaire 9 (PHQ-9) and Lee Symptom Burden (LSB) scale.
      RESULTS: Myofascial (p<.001) and lung (p=.001) involvement, 2-Minute Walk test
      (p<.001), LSB (p<.001) and PHQ-9 (p=.03) had the largest associations with KPS
      with liver (p=.05) and hand grip strength (p<.001) more modest associations with
      KPS. CONCLUSIONS: Patients with cGVHD experience multifactorial impairment in
      function associated with potentially modifiable symptoms physiatrists have the
      expertise to address to enhance function. More research is needed to determine
      rehabilitation interventions to mitigate the impact of cGVHD on function.

PMID- 30205084
TI  - The Computerized ECG: Friend and Foe.
AB  - Computerized interpretation of the electrocardiogram (ECG) began in the 1950's
      when conversion of its analog signal to digital form became available. Since then
      automatic computer interpretations of the ECG have become routine, even at the
      point of care, by the addition of interpretive algorithms to portable ECG carts.
      Now, >100 million computerized ECG interpretations are recorded yearly in the
      USA. These interpretations have contributed to medical care by reducing physician
      reading time and accurately interpreting most normal ECG's. But errors do occur.
      The computer cannot be held responsible for misinterpretations due to recording
      errors i.e. muscle artifacts or lead reversal. But in many abnormal ECGs, the
      computer makes its own errors - sometimes critical - in its incorrect detection
      of arrhythmias, pacemakers and myocardial infarctions. These errors require that
      all computerized statements be over read by trained physicians who have the
      advantage of clinical context, unavailable to the computer. Together, the
      computer and over readers now provide the most accurate ECG interpretations
      available.

PMID- 30205085
TI  - Role of the glutaredoxin domain and FAD in the stabilization of thioredoxin
      glutathione reductase.
AB  - Thioredoxin glutathione reductase (TGRsec) is a multi-domain flavoprotein that
      plays a principal role in redox homeostasis maintenance. We have previously
      demonstrated the role of selenocysteine in maintaining TGRsec structure-function,
      but the role of the glutaredoxin (Grx) domain and FAD is still unclear. In the
      present study, the urea-induced unfolding of recombinant Fasciola gigantica
      TGRsec (FgTGRsec) and its N-terminal truncated variant (DeltaNTD-FgTGRsec) were
      examined to understand the role of the Grx domain and FAD in the stabilization of
      FgTGRsec and DeltaNTD-FgTGRsec. Our results showed that both proteins underwent
      unfolding in a three state manner. First, the protein undergoes a conformational
      transition rendering a near-native state with no FAD bound, and then full
      unfolding of the apo-dimer occurs without dissociation. The Grx domain stabilized
      the global FgTGRsec structure and positively regulated FgTGRsec activity, and
      alteration in the FAD microenvironment was directly proportional to the loss of
      thioredoxin reductase (TrxR) and glutathione reductase activities. Based on these
      results, we concluded that the Grx domain stabilizes the full-length FgTGRsec
      protein for efficient catalysis. Thus, we suggest that in platyhelminth
      parasites, during evolution, the Grx domain merged with the TrxR domain to confer
      higher catalytic activity and provide additional structural stability to the full
      length TGR.

PMID- 30205087
TI  - Tumor-endothelial cell interaction in an experimental model of human
      hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is a densely vascularized tumor that is highly
      dependent on angiogenic pathways to direct arterial blood flow to the growing
      neoplasm, though little is known about how the interaction of tumor and
      endothelial cells drives these processes and the degree of clinical importance.
      To this end, we examined the intercellular cross-talk between HepG2 (human HCC)
      and human endothelial progenitor cells (EPC) in a co-culture system that mimics
      some aspects of initial tumor parenchyma and stroma interactions. The results
      showed that the remote cell-to-cell (paracrine) interactions between HepG2 cells
      and EPC play a critical role in the differentiation and angiogenic activity of
      endothelial cells, possibly through intercellular signaling function of the
      exosomes released in the medium by HepG2 cells. The tumor-cell activated
      phenotype of EPC was associated with increased migration and elevated expression
      of ephrin-B2, and Delta-like 4 ligand (DLL4). Furthermore, ephrin-B2 was found to
      be overexpressed in HCC and cholangiocarcinoma tissue samples taken from humans.
      Overall, our results demonstrate that ephrin-B2 and Dll4 mediated co-dependence
      of HCC and EPC intercellular crosstalk in the initial stages of HCC establishment
      and development, a promising target for new clinical strategies.

PMID- 30205088
TI  - Follicular helper T cells promote the effector functions of CD8+ T cells via the
      provision of IL-21, which is downregulated due to PD-1/PD-L1-mediated suppression
      in colorectal cancer.
AB  - Recent studies have demonstrated that higher expression of follicular helper T
      cell (Tfh)-associated genes is associated with better prognosis in breast cancer
      and colorectal cancer (CRC), but the underlying mechanisms remain unclear. In
      this study, we compared the function of Tfh cells in non-cancer (NC) controls and
      in CRC patients between stages II and IV. Data showed that the level of
      CD4+CXCR5+ Tfh cells were significantly upregulated in stage II CRC patients but
      was progressively reduced in stage III and stage IV patients. The frequency of PD
      1+ cells in CD4+CXCR5+ Tfh cells, on the other hand, was progressively increased
      from NC patients to CRC patients with increasing severity. Interestingly, the
      CD4+CXCR5+PD-1- Tfh cells, but not the CD4+CXCR5+PD-1+ Tfh cells, promoted the
      CD107a expression and IFN-gamma expression by CD8+ T cells. This CD8+ T cell
      promoting capacity was dependent on the expression of IL-21, as this capacity was
      significantly impaired by IL-21 neutralization. Tfh cells from CRC patients with
      advanced stages presented gradual reduction in the capacity to stimulate CD8+ T
      cells and the capacity to produce IL-21. In addition, treatment with autologous
      PD-L1-expressing tumor cells further suppressed the IL-21 expression by PD-1+ Tfh
      cells. Together, these data demonstrated that Tfh cells potently enhanced the
      effector functions of CD8+ T cells in an IL-21-dependent pathway; however, this
      role of Tfh cells was limited in CRC patients due to PD-1/PD-L1-mediated
      suppression.

PMID- 30205086
TI  - Analyzing the function of the insert region found between the alpha and beta
      subunits in the eukaryotic nitrile hydratase from Monosiga brevicollis.
AB  - The functional roles of the (His)17 region and an insert region in the eukaryotic
      nitrile hydratase (NHase, EC 4.2.1.84) from Monosiga brevicollis (MbNHase), were
      examined. Two deletion mutants, MbNHaseDelta238-257 and MbNHaseDelta219-272, were
      prepared in which the (His)17 sequence and the entire insert region were removed.
      Each of these MbNHase enzymes provided an alpha2beta2 heterotetramer, identical
      to that observed for prokaryotic NHases and contains their full complement of
      cobalt ions. Deletion of the (His)17 motif provides an MbNHase enzyme that is
      ~55% as active as the WT enzyme when expressed in the absence of the Co-type
      activator (epsilon) protein from Pseudonocardia thermophila JCM 3095 (PtNHaseact)
      but ~28% more active when expressed in the presence of PtNHaseact.
      MbNHaseDelta219-272 exhibits ~55% and ~89% of WT activity, respectively, when
      expressed in the absence or presence of PtNHaseact. Proteolytic cleavage of
      MbNHase provides an alpha2beta2 heterotetramer that is modestly more active
      compared to WT MbNHase (kcat = 163 +/- 4 vs 131 +/- 3 s-1). Combination of these
      data establish that neither the (His)17 nor the insert region are required for
      metallocentre assembly and maturation, suggesting that Co-type eukaryotic NHases
      utilize a different mechanism for metal ion incorporation and post-translational
      activation compared to prokaryotic NHases.

PMID- 30205089
TI  - Utility of amniotic fluid chitotriosidase in the prenatal diagnosis of lysosomal
      storage disorders.
AB  - OBJECTIVE: Plasma chitotriosidase is a documented biomarker for certain lysosomal
      storage disorders. However, its clinical utility for prenatal samples is not
      elucidated yet. METHODS: We have established Reference intervals for amniotic
      fluid chitotriosidase using control amniotic fluids (n = 47) and compared the
      activity with amniotic fluids affected by lysosomal storage disorders (n = 25).
      RESULTS: The reference interval established was 0-6.76 nmol/h/ml. The amniotic
      fluids affected with LSDs exhibited elevation of chitotriosidase. The area under
      the curve (AUC) of receiver operating characteristic curve for affected vs.
      healthy was 0.987 indicating 98.6% accuracy of chitotriosidase in identifying
      pregnancies affected with LSDs. Among the different LSDs, Gaucher (202.00 +/-
      35.27 nmol/h/ml) and Niemann-pick A/B (60.33 +/- 21.59 nmol/h/ml) showed very
      high levels of chitotriosidase. CONCLUSION: Amniotic fluid chitotriosidase has
      the potential to serve as a diagnostic marker for lysosomal storage disorders,
      more specifically for Gaucher and Niemann-Pick A/B.

PMID- 30205090
TI  - Incremental value of intact fibroblast growth factor 23 to natriuretic peptides
      for long-term risk estimation of heart failure patients.
AB  - Fibroblast growth factor 23 (FGF-23), a key hormone for the regulation of the
      phosphorus homeostasis, has also several direct effects on cardiac function. In
      heart failure (HF), the increase of FGF-23 participates to cardiac hypertrophy
      and remodeling. Measurement of the intact, biologically active hormone is now
      available. We determined intact FGF-23 in HF patients with reduced ejection
      fraction and assess its prognosis value for cardiovascular death over a long-term
      follow-up. We observed that intact FGF-23 is an independent predictor of
      cardiovascular death in HF patients and provides added value to the standard of
      care, natriuretic peptide, for risk estimation.

PMID- 30205091
TI  - Methadone Metabolism and Drug-Drug Interactions: In Vitro and In Vivo Literature
      Review.
AB  - Methadone is utilized for the treatment of individuals with opiate dependence.
      Methadone undergoes N-demethylation by multiple cytochrome P450 (CYP) enzymes
      including CYP3A4, CYP2B6, CYP2C19, CYP2D6, CYP2C9, and CYP2C8. In vivo,
      polymorphism effects on methadone systemic exposure have been noted for CYP2B6,
      CYP3A4, and CYP2D6. Clinical drug interaction studies with antiviral drugs in
      methadone maintenance treatment patients yield varying results on methadone
      pharmacokinetics and pharmacodynamics. In general, CYP inhibitors altered
      methadone exposure with no adverse effects. CYP inducers generally decreased
      methadone exposure with some reports of withdrawal symptoms in the subjects.
      Interaction studies with antiviral drug combinations yielding differing results
      depend on the enzyme(s) affected. For certain antiviral medicines which are dual
      inhibitor(s) and inducer(s) for CYP enzymes, their effect on methadone
      pharmacokinetics can change with time since the effect of induction is usually
      delayed compared to the effect of inhibition.

PMID- 30205092
TI  - Structural Basis of Epitope Recognition by Heavy-Chain Camelid Antibodies.
AB  - Truncated versions of heavy-chain antibodies (HCAbs) from camelids, also termed
      nanobodies, comprise only one-tenth the mass of conventional antibodies, yet
      retain similar, high binding affinities for the antigens. Here we analyze a large
      data set of nanobody-antigen crystal structures and investigate how nanobody
      antigen recognition compares to the one by conventional antibodies. We find that
      nanobody paratopes are enriched in aromatic residues just like conventional
      antibodies, but additionally, they also bear a more hydrophobic character. Most
      striking differences were observed in the characteristics of the antigen's
      epitope. Unlike conventional antibodies, nanobodies bind to more rigid, concave,
      conserved and structured epitopes enriched with aromatic residues. Nanobodies
      establish fewer interactions with the antigens compared to conventional
      antibodies, and we speculate that high binding affinities are achieved due to
      less unfavorable conformational and more favorable solvation entropy
      contributions. We observed that interactions with antigen are mediated not only
      by three CDR loops but also by numerous residues from the nanobody framework.
      These residues are not distributed uniformly; rather, they are concentrated into
      four structurally distinct regions and mediate mostly charged interactions. Our
      findings suggest that in some respects nanobody-antigen interactions are more
      similar to the general protein-protein interactions rather than antibody-antigen
      interactions.

PMID- 30205093
TI  - Folic acid magnetic nanotheranostics for delivering doxorubicin: Toxicological
      and biocompatibility studies on Zebrafish embryo and larvae.
AB  - Doxorubicin (DOXO) is a chemotherapeutic agent widely used for the treatment of
      solid tumors and hematologic malignancies in both adults and children. However,
      DOXO causes short- and long-term cardiotoxicity and others undesirable side
      effects, such as nephrotoxicity and neurotoxicity. Magnetic nanoparticles (MNPs)
      allow the delivery of drugs specifically to target place, employing an external
      magnet. Moreover, they may act as contrast agents in MRI providing information on
      the diagnostic of diverse pathologies. In this way, two functions may be combined
      in a unique nanosystem known as theranostic. Also, the MNPs can be modified with
      folic acid (MNPs@FA) to increase the uptake by cancer cells that overexpress the
      FA receptors. In previous works, our collaborators obtained and characterized
      MNPs, MNPs@FA, and MNPs@FA@DOXO. It is essential to study the biosafety of
      nanotheranostic, and there is no published study of Fe3O4 nanoparticles
      developmental toxicity. Because of that, this work aimed to study the in vivo
      toxicity and biocompatibility of DOXO, MNPs@FA, and MNPs@FA@DOXO using zebrafish
      embryo and larvae as an animal model. Viability, developmental toxicity, changes
      in spontaneous movement (neurotoxicity), changes in cardiac rhythm
      (cardiotoxicity), and efficiency of DOXO-uptake were studied. While the 48-h
      treatment with 50 MUg/mL of DOXO resulted in a 30% larvae death and the
      development of significant morphological abnormalities, the treatment with
      MNPs@FA@DOXO and MNPs@FA did not reduce the viability and did not cause
      developmental abnormalities. Besides, the MNPs@FA@DOXO reduced the cardiotoxicity
      and promoted a more rapid and significant uptake of DOXO by zebrafish larvae.

PMID- 30205094
TI  - Macro scale modelling of cortical spreading depression and the role of astrocytic
      gap junctions.
AB  - Neuronal activity evokes a localised increase in cerebral blood flow in a
      response known as neurovascular coupling (NVC), achieved through communication
      between a group of cells known as a neurovascular unit (NVU). Dysfunctional NVC
      can lead to pathologies such as cortical spreading depression (CSD),
      characterised by a slow moving wave of neuronal depolarisation and high
      extracellular K+ levels. This phenomenon can be affected by the presence of an
      astrocytic gap junction network which is able to transport K+ away from areas of
      high concentrations, however the precise role of these gap junctions remains
      controversial. In this study, a large scale numerical NVC model of a vascular
      tree coupled with multiple NVUs comprising a two-dimensional cerebral tissue
      slice is extended through extracellular K+ and Na+ electrodiffusion and K+
      transport via an astrocytic gap junction network. An updated NVU model has been
      utilised that contains complex neuronal and extracellular dynamics and is able to
      simulate various pathologies such as CSD and the effect on the vascular response.
      Under pathological conditions (determined by model parameters) and with
      extracellular electrodiffusion the model is able to simulate a propagating wave
      of high extracellular K+ travelling at 6.7 mm/min as can occur in CSD. This wave
      travels outward from the neuronally stimulated area and is followed by a wave of
      vasoconstriction (with corresponding decreased blood flow) then slight
      vasodilation in agreement with multiple experimental results. The
      vasoconstrictive wave peaks after the K+ wave due to the delayed vascular
      response. Increasing the density of astrocytic gap junctions reduces the duration
      and amplitude of the vasoconstrictive wave and for high enough density the
      vasoconstrictive behaviour outside the stimulated area is eliminated. Gap
      junctions also reduce the area that is initially affected by vasoconstriction.
      This in silico model provides a complex and experimentally validated test bed for
      a variety of neurological phenomena.

PMID- 30205095
TI  - A coupled bulk-surface model for cell polarisation.
AB  - Several cellular activities, such as directed cell migration, are coordinated by
      an intricate network of biochemical reactions which lead to a polarised state of
      the cell, in which cellular symmetry is broken, causing the cell to have a well
      defined front and back. Recent work on balancing biological complexity with
      mathematical tractability resulted in the proposal and formulation of a famous
      minimal model for cell polarisation, known as the wave pinning model. In this
      study, we present a three-dimensional generalisation of this mathematical
      framework through the maturing theory of coupled bulk-surface semilinear partial
      differential equations in which protein compartmentalisation becomes natural. We
      show how a local perturbation over the surface can trigger propagating reactions,
      eventually stopped in a stable profile by the interplay with the bulk component.
      We describe the behavior of the model through asymptotic and local perturbation
      analysis, in which the role of the geometry is investigated. The bulk-surface
      finite element method is used to generate numerical simulations over simple and
      complex geometries, which confirm our analysis, showing pattern formation due to
      propagation and pinning dynamics. The generality of our mathematical and
      computational framework allows to study more complex biochemical reactions and
      biomechanical properties associated with cell polarisation in multi-dimensions.

PMID- 30205096
TI  - Malaysian propolis, metformin and their combination, exert hepatoprotective
      effect in streptozotocin-induced diabetic rats.
AB  - AIMS: Hepatic oxidative stress and weak antioxidant defence system resulting in
      hepatic lesion, has been reported in diabetic rats. The present study
      investigated the possible hepatoprotective effects of Malaysian propolis (MP) in
      diabetic rats, on the background that MP has been reported to have anti
      hyperglycemic, antioxidant and anti-inflammatory effects. MATERIALS AND METHODS:
      Sprague-Dawley rats were randomly divided into 5 groups, namely: normal control
      (NC), diabetic control (DC), diabetic on 300 mg/kg b.w. MP, diabetic on 300 mg/kg
      b.w. metformin, and diabetic on MP and metformin combined therapy. Treatment was
      done orally for 4 weeks, and NC and DC groups received distilled water as
      vehicle. KEY FINDINGS: Results showed increased fasting blood glucose and serum
      markers of hepatic lesion (aspartate aminotransferase, alkaline phosphatase,
      alanine aminotransferase and gamma-glutamyl transferase), increased hepatic
      lactate dehydrogenase activity, decreased hepatic superoxide dismutase, catalase,
      glutathione peroxidase, glutathione-S-transferase and glutathione reductase
      activities, increased immunoexpressions of nuclear factor kappa B, tumor necrosis
      factor-alpha, interleukin(IL)-1beta and caspase-3, and decreased
      immunoexpressions of IL-10 and proliferating cell nuclear antigen in the liver of
      DC group. Histopathology of the liver revealed numerous hepatocytes with pyknotic
      nuclei and inflammatory infiltration, while periodic acid-schiff staining
      decreased in the liver of DC group. Treatment with MP attenuated these negative
      effects and was comparable to metformin. Furthermore, these effects were better
      attenuated in the combined therapy-treated diabetic rats. SIGNIFICANCE: Malaysian
      propolis attenuates hepatic lesion in DM and exerts a synergistic protective
      effect with the anti-hyperglycemic medication, metformin.

PMID- 30205098
TI  - Profound Diarrhea Following Cholecystectomy.

PMID- 30205097
TI  - Protective effects of sodium nitrate against testicular apoptosis and
      spermatogenesis impairments in streptozotocin-induced diabetic male rats.
AB  - AIMS: As nitric oxide (NO) production is essential for insulin signaling, glucose
      uptake, endothelial function, and regulation of apoptosis, the loss of
      bioavailable NO may be a mechanism underlying the development of diabetes
      complication. Dietary nitrate acts as a substrate for NO generation, thus serving
      as a physiological source of NO. This study evaluated the therapeutic effects of
      nitrate supplementation on the apoptosis-induced testicular disorders in diabetic
      rats. MAIN METHODS: Fifty male Wistar rats were divided into five groups;
      control, control with 100 mg/L nitrate in distilled drinking water, diabetes,
      diabetes treated with 2-4 U/day NPH insulin, diabetes treated with 100 mg/L
      nitrate in distilled drinking water. After 8 weeks, blood samples, testis, and
      epididymis were collected to assess the apoptosis process and the stereology of
      testis tissue, sperm motility, morphology and DNA fragmentation, and also mRNA
      expression of miR-449a, p53, Pdcd4, and Pacs2 mRNA, as well as serum glucose,
      insulin, and NOx levels were investigated. KEY FINDINGS: The results of this
      study indicated that nitrate treatment ameliorated the sperm parameters,
      testicular morphometrical and stereological alterations, reduced blood glucose,
      the number of TUNEL positive cells and tubules, and testicular expressions of
      p53, Pdcd4, and Pacs2 mRNA as well as increased body weight, serum insulin and
      NOx levels, and testicular expression of miR-449a in streptozotocin-induced
      diabetic rats. SIGNIFICANCE: Our in vivo evidence revealed that nitrate treatment
      may has a favorable effect as an exogenous NO donor on experimental diabetic
      testicular damages in which NO bioavailability is impaired.

PMID- 30205099
TI  - A Surprising Cause for Intestinal Obstruction.

PMID- 30205100
TI  - Edematous Colitis of an Unknown Cause, Diagnosis by Pattern Recognition.

PMID- 30205101
TI  - Severe Acute Gastrointestinal Bleed in a Patient with Neurofibromatosis Type-1.

PMID- 30205102
TI  - A Case Report of a Young Adult With Progressive Bloody Diarrhea, Protein-Losing
      Enteropathy, and Extended Polyposis Coli.

PMID- 30205104
TI  - Should We Separate the Pulmonary Surveillance Protocol for Postsurgical T1a and
      T1b Renal Cell Carcinoma? A Multicenter Database Analysis.
AB  - OBJECTIVE: To investigate the incidence of pulmonary metastases (PM) and the
      utility of the surveillance chest radiography (CXR) in detecting PM after
      curative treatment to better define surveillance recommendations for T1a and T1b
      renal cell carcinoma. MATERIALS AND METHODS: A retrospective review of a multi
      institutional database was performed to include patients with renal masses
      treated with partial nephrectomy or radical nephrectomy. Patients were excluded
      for >=T2 disease, benign pathology, and metastases. The primary outcome was the
      incidence of asymptomatic pulmonary lesion concerning for PM detected by CXR
      within 3 years. RESULTS: Five hundred sixty-eight patients met criteria of which
      384 had T1a and 184 had T1b at a mean follow-up of 45 and 43 months,
      respectively. Patients averaged 2.96 and 2.99 CXRs for T1a and T1b with 46.8%
      having surveillance beyond 3 years. Indeterminate lesions were found in 5.7% (22)
      of T1a and 5.4% (10) in T1b of which 0.01% (2) and 1.1% (2) were confirmed PM by
      chest computed tomography and biopsy. Three-year CXR surveillance period detected
      asymptomatic PM in zero and two patients for T1a and T1b, respectively. High risk
      pathological features were not present in patients with PM. There was no
      difference in the incidence PM for patients undergoing partial nephrectomy
      (3/290) or radical nephrectomy (1/278) (P = .62). CONCLUSION: Our review suggests
      that post-treatment pulmonary surveillance should be reserved for T1b and may not
      be required for T1a given the low yield and false positives of CXR leading to
      unnecessary radiation and potential biopsies.

PMID- 30205103
TI  - Streptocyclinones A and B ameliorate Alzheimer's disease pathological processes
      in vitro.
AB  - Alzheimer's disease (AD) is a pathology characterized by the abnormal
      accumulation of amyloid-beta (Abeta) and hyperphosphorylated tau. Oxidative
      stress and neuroinflammation are also strongly related to this disease. The
      ability of two new glycosylated angucyclinones, streptocyclinones A and B (1 and
      2), isolated from Streptomyces sp to improve AD hallmarks was evaluated.
      Compounds were able to protect SH-SY5Y neuroblastoma cells from H2O2-induced
      oxidative injury by activating the nuclear factor E2-related factor (Nrf2). Their
      capacity to modulate neuroinflammation was tested in lipopolysaccharide-activated
      BV2 microglial cells. Compounds reduced the release of pro-inflammatory factors,
      inhibited the activation of NFkappaB and mitogen activated kinases (MAPK), and
      induced the translocation of Nrf2 to the nucleus of microglial cells. A trans
      well co-culture was established to determine the effect of microglia treated with
      streptocyclinones on the survival of SH-SY5Y cells. The cell viability of
      neuroblastoma cells increased when the compounds were added to BV2 cells. SH-SY5Y
      TMHT441 cells were used to determine the effect of compounds on tau
      phosphorylation. Both compounds reduced tau hyperphophorylation by targeting MAPK
      kinases. Moreover, streptocyclinone B (2) was able to inhibit the activity of
      beta-secretase 1 and decrease the release of reactive oxygen species in BV2 cells
      stimulated with Abeta. With the same co-culture trans-well system, the treatment
      of Abeta-stimulated microglia with compound 2 augmented the viability of SH-SY5Y
      TMHT441 cells. The results presented in this work provide evidences of the
      multitarget activities displayed by these new Streptomyces compounds, making them
      good candidates for further studies in the treatment of AD.

PMID- 30205105
TI  - Antimuscarinic Use in Men Treated With Bladder Outlet Obstruction Medication
      Therapy.
AB  - OBJECTIVE: To assess changes over time in the use of antimuscarinics (AM) among
      visits in adult men treated with bladder outlet obstruction (BOO) medication
      therapy (ie, alpha blocker and 5-alpha reductase inhibitors). METHODS: We used
      the National Ambulatory Medicare Care Survey database (2006-2014) to identify men
      aged 40 or older, who initiated or continued on BOO medication therapy. Among
      these visits, we assessed the percentage of AM and evaluated trends of AM use
      across between 2006 and 2014 using multivariable logistic regression. RESULTS:
      Overall, there were 7561 patient visits in men aged 40 or older, who were treated
      with BOO medication therapy between 2006 and 2014 which equates to approximately
      158 million visits in the United States after incorporating National Ambulatory
      Medicare Care Survey weights. Overall, AM was used in 3.7% of visits, among those
      who were treated with BOO medication therapy; use of AM increased with age. In
      the multivariable analysis, there was no increasing trend in the use of AM in
      2006 relative to subsequent years through 2014 (P = .8104). CONCLUSION: Despite a
      previous study that showed an increasing trend in antimuscarinic use among
      patients coded for lower urinary tract symptoms or benign prostatic hyperplasia
      between 1993 and 2010, several recent randomized-controlled trials, and a
      recommendation in a clinical practice guideline in 2010, we found no increasing
      trend in antimuscarinic use among visits in men who were treated with BOO
      medication therapy in 2006 compared to subsequent years. This suggests the
      potential undertreatment of antimuscarinics and an area for improved prescribing.

PMID- 30205106
TI  - A comprehensive three-dimensional assay to assess neutrophil defense against
      bacteria.
AB  - Neutrophil antibacterial capacity is measured in animal models and in vitro as an
      important indicator of neutrophil function. To be able to extrapolate their
      conclusions, in vitro experiments should mimic the in vivo situation. In vivo,
      antibacterial capacity depends on multiple steps of bacterial sensing, priming,
      chemotaxis, phagocytosis and intracellular killing. Therefore, we developed a
      simply executed assay that involves multiple steps in one assay. The neutrophils
      were incorporated into a three-dimensional matrix of fibrin fibers, in which they
      could freely migrate. The fibrin matrix provided a more physiological
      representation of tissue structure than a shaken suspension and extended ex vivo
      survival of neutrophils. Staphylococci endogenously producing GFP (Green
      Fluorescent Protein) provided a real-time quantification of the bacterial load
      without the need for lysing the fibrin matrix or counting of colony forming units
      on agar plates. The delay in bacterial outgrowth serves as a measure for the
      relative antibacterial capacity of the neutrophils. Additionally, neutrophil
      capacity could easily be measured high-throughput in a 96-wells format. In this
      new assay we study neutrophil behavior in a physiologically relevant setting and
      explore many functions of the neutrophil in a single test. The functional
      capacity of neutrophils from different in vitro treatments or different donors
      can directly be compared.

PMID- 30205108
TI  - Role of medial hypothalamic orexin system in panic, phobia and hypertension.
AB  - Orexin has been implicated in a number of physiological functions, including
      arousal, regulation of sleep, energy metabolism, appetitive behaviors, stress,
      anxiety, fear, panic, and cardiovascular control. In this review, we will
      highlight research focused on orexin system in the medial hypothalamic regions of
      perifornical (PeF) and dorsomedial hypothalamus (DMH), and describe the role of
      this hypothalamic neuropeptide in the behavioral expression of panic and
      consequent fear and avoidance responses, as well as sympathetic regulation and
      possible development of chronic hypertension. We will also outline recent data
      highlighting the clinical potential of single and dual orexin receptor
      antagonists for neuropsychiatric conditions including panic, phobia, and
      cardiovascular conditions, such as in hypertension.

PMID- 30205107
TI  - Anticonvulsant effects after grafting of rat, porcine, and human mesencephalic
      neural progenitor cells into the rat subthalamic nucleus.
AB  - Cell transplantation based therapy is a promising strategy for treating
      intractable epilepsies. Inhibition of the subthalamic nucleus (STN) or substantia
      nigra pars reticulata (SNr) is a powerful experimental approach for remote
      control of different partial seizure types, when targeting the seizure focus is
      not amenable. Here, we tested the hypothesis that grafting of embryonic/fetal
      neural precursor cells (NPCs) from various species (rat, human, pig) into STN or
      SNr of adult rats induces anticonvulsant effects. To rationally refine this
      approach, we included NPCs derived from the medial ganglionic eminence (MGE) and
      ventral mesencephalon (VM), both of which are able to develop a GABAergic
      phenotype. All VM- and MGE-derived cells showed intense migration behavior after
      grafting into adult rats, developed characteristics of inhibitory interneurons,
      and survived at least up to 4 months after transplantation. By using the
      intravenous pentylenetetrazole (PTZ) seizure threshold test in adult rats,
      transient anticonvulsant effects were observed after bilateral grafting of NPCs
      derived from human and porcine VM into STN, but not after SNr injection (site
      specificity). In contrast, MGE-derived NPCs did not cause anticonvulsant effects
      after grafting into STN or SNr (cell-specificity). Neither induction of status
      epilepticus by lithium-pilocarpine to induce neuronal damage prior to the PTZ
      test nor pretreatment of MGE cells with retinoic acid and potassium chloride to
      increase differentiation into GABAergic neurons could enhance anticonvulsant
      effectiveness of MGE cells. This is the first proof-of-principle study showing
      anticonvulsant effects by bilateral xenotransplantation of NPCs into the STN. Our
      study highlights the value of VM-derived NPCs for interneuron-based cell grafting
      targeting the STN.

PMID- 30205109
TI  - Glutathione peroxidase 4 participates in secondary brain injury through mediating
      ferroptosis in a rat model of intracerebral hemorrhage.
AB  - Oxidative stress plays an important role in secondary brain injury (SBI) after
      intracerebral hemorrhage (ICH), but the underling mechanism has not been fully
      elucidated. Recently, the antioxidant enzyme glutathione peroxidase 4 (GPX4), has
      attracted increasing attention due to its ability to degrade reactive oxygen
      species (ROS) which are the major indicator of oxidative stress; However, the
      role of GPX4 in ICH has not been reported. This study was designed to investigate
      the changes in protein levels, as well as potential role and mechanism of GPX4 in
      SBI following ICH using a Sprague-Dawley (SD) rat model of ICH induced by
      autologous blood injection into the right basal ganglia. Firstly, GPX4 protein
      levels in the brain were reduced gradually and bottomed out at 24 h after ICH,
      compared with the Sham group. Secondly, genetic-overexpression of GPX4
      effectively increased level of GPX4 in the brain, and clearly relieved neuronal
      dysfunction, brain edema, blood brain barrier (BBB) injury, oxidative stress and
      inflammation after ICH. In contrast, inhibiting GPX4 with a specific
      pharmacological inhibitor or genetic knockdown exacerbated SBI after ICH.
      Finally, Ferrostatin-1, a chemical inhibitor of ferroptosis, was used to explore
      the role of ferroptosis in brain injury after ICH. The results suggest that
      inhibiting ferroptosis can significantly alleviate SBI after ICH. In summary, our
      work indicated that GPX4 contributes to SBI following ICH by mediating
      ferroptosis. Therefore, inhibiting ferroptosis with specific inhibitors or
      upregulation of GPX4 may be a potential strategy to ameliorate brain injury
      induced by ICH.

PMID- 30205110
TI  - Pathogenic role of autoantibodies against inhibitory synapses.
AB  - Diverse neuropsychiatric diseases were recently linked to specific anti-neuronal
      autoantibodies targeting synaptic proteins. Symptoms can range from epileptic
      seizures to cognitive impairment to movement disorders, commonly responding to
      treatment with immunotherapy. Several of these autoantibodies target inhibitory
      synapses that use GABA or glycine as neurotransmitters. Despite their relatively
      low abundance, inhibitory neurons are extraordinarily diverse in anatomical,
      electrophysiological and molecular terms, reflecting the variable clinical
      phenotypes of affected patients. Indeed, data on the antibody effects in neuronal
      cultures or animals models suggest that most of these antibodies are directly
      pathogenic by down-regulating synaptic proteins, activating complement or
      antagonizing ligand binding. The present review summarizes the current
      achievements in the field of humoral autoimmunity related to inhibitory networks,
      state-of-the-art diagnostics and clinical characterization of patients. In many
      instances, the phenotypic spectrum of patients with GABA receptor, glycine
      receptor, amphiphysin or GAD65 antibodies mirror the experimental findings,
      suggesting that ongoing work will markedly contribute to the better understanding
      of pathophysiology in this exciting patient group and might pave the way for
      disease-specific immunotherapy.

PMID- 30205111
TI  - How orexin signals bias action: Hypothalamic and accumbal circuits.
AB  - Survival-maximizing, well-timed actions are a key responsibility of the brain.
      Hypothalamic neurons containing neurotransmitters orexins/hypocretins are
      important players in this process. Individuals without orexin neurons display
      inappropriately-timed transitions between arousal states, and other behavioural
      abnormalities including increased risk-taking. Deciphering neural circuits
      through which orexin neurons control brain states and behavior thus illuminates
      brain mechanisms of context-appropriate actions. This review outlines and puts
      into broader context recent examples of orexin circuit analyses in the lateral
      hypothalamus (LH) and the nucleus accumbens (NAc), two brain regions clasically
      implicated in context-appropriate actions. In the LH, orexin neurons excite GAD65
      expressing neurons. The LH(GAD65) neuron excitation induces elevated locomotor
      activity, while inhibition of LH(GAD65) neuron natural activity depresses
      voluntary locomotion. The orexin -> LH(GAD65) circuit may therefore assist in
      creating the drive to run. In the NAc shell region, orexin axons excite D2
      neurons (dopamine-inhibited neurons expressing dopamine type-2 receptor). NAc(D2)
      cell activation increases risk-avoidance behaviors, while NAc(D2) cell inhibition
      reduces risk-avoidance. The excitatory orexin -> NAc(D2) circuit may thus assist
      in reducing risk-taking, and oppose the inhibitory VTA(dopamine) -> NAc(D2)
      circuit during computation of risk appetite. Neural computation in these local
      and long-range orexin circuits may thus assist in generating risk-avoiding
      locomotor responses to stressors known to activate orexin neurons, such as body
      energy depletion or potential external threats. A model is proposed where orexin
      opposing, inhibitory inputs acting on the orexin target neurons may context
      specifically channel orexin-induced brain excitation towards particular sets of
      actions.

PMID- 30205112
TI  - Implementation of fluorescence anisotropy-based assay for the characterization of
      ligand binding to dopamine D1 receptors.
AB  - Dopamine receptors, which belong to the family of G protein-coupled receptors,
      are very substantial regulators in the brain and therefore important targets in
      drug discovery. Radioligand binding assay has been the method of choice for
      screening novel dopaminergic drugs for decades. We demonstrate that fluorescent
      ligand BodipyFL-SKF83566 binding to dopamine D1 receptors expressed in budded
      baculovirus particles can be characterized with fluorescent anisotropy (FA) based
      assay and that this is a valuable alternative to the radioligand binding assay.
      High binding affinity (KD = 5.2 nM) and fast association and dissociation
      kinetics (half-lives 40 s and 70 s, respectively) make BodipyFL-SKF83566 a
      suitable fluorescent ligand for this type of experiments. Good correlation
      between pKi values of 11 different dopaminergic ligands determined in competition
      binding experiments with radioligand [3H]SCH23390 or BodipyFL-SKF83566 (R2 =
      0.96, slope not significantly different from unity) further validates the FA
      assay. In addition to competitor's affinity, the method also enables to quantify
      the apparent pIC50 values in time and hence kinetic properties of an unlabeled
      ligand can be estimated from the same competition binding experiment. Due to the
      homogenous nature of the FA assay reactions can be monitored in real time without
      any risk of precipitation of receptors in budded baculovirus particles. Despite
      the lack of coupled G proteins, the proposed novel assay system allows on-line
      monitoring of ligand binding to dopamine D1 receptors that could be easily
      applicable in early drug screening.

PMID- 30205113
TI  - Lung Transplantation From Donation After Circulatory Death: United States and
      Single-Center Experience.
AB  - BACKGROUND: Lung transplants from donation after circulatory death (DCD) have
      been scarcely used in the United States. Concerns about the warm ischemic injury,
      resource mal-utilization due to the uncertain timing of death, and public
      scrutiny may be some factors involved. METHODS: Survival for recipients of a
      donation after brain death (DBD) versus DCD was analyzed by using the United
      Network for Organ Sharing and our institutional database. A propensity-matching
      and Cox regression analysis was performed for 25 characteristics. Primary graft
      dysfunction metrics were compared. RESULTS: A total of 389 of 20,905 lung
      transplantations (2%) were performed by using DCDs in the United States, and 15
      of 128 (12%) at our institution. Five and 10-year survival for DBDs was 55% and
      30% and 59% and 33% for DCDs, respectively. Propensity-matched analysis of 311
      DBD/DCD pairs did not demonstrate any difference in survival. On Cox regression,
      DCD was not associated with impaired survival. Male sex, Karnofsky class greater
      than 50, double lung transplantation, and transplantation year were predictors of
      improved survival. Age, creatinine, pulmonary fibrosis, retransplantation,
      extracorporeal membrane oxygenation, allocation score, and donor age were
      predictors of worse survival. Primary graft dysfunction at time 0 was worse for
      recipients of DCDs (p = 0.005) but equivalent at 24, 48, and 72 hours.
      CONCLUSIONS: DCD lung transplants remain underused in the United States.
      Nevertheless, survival is similar to DBD. Primary graft dysfunction metrics for
      DCDs are worse than DBDs on intensive care arrival but improved subsequently.

PMID- 30205114
TI  - Long-Term Outcomes of Coarctation Repair Through Left Thoracotomy.
AB  - BACKGROUND: Optimal surgical approach for repair of coarctation of the aorta
      (CoA) remains controversial. This study aimed to evaluate reintervention rates
      and its predictors by using a strategy of resection with extended end-to-end
      anastomosis (REEEA) through left thoracotomy. METHODS: A retrospective analysis
      was performed for all patients who underwent isolated CoA repair or simultaneous
      repair of CoA and ventricular septal defect repair by REEEA between January 2000
      and December 2015 at Ann & Robert H. Lurie Children's Hospital of Chicago,
      Chicago, Illinois. Patients with complex congenital heart disease were excluded.
      Transverse arch hypoplasia was defined as echocardiographic z-score lower than -2
      or by documentation in medical or operative reports. Reintervention was defined
      as the need for balloon angioplasty or reoperation. Hypertension was defined as
      antihypertensive medication use or blood pressure greater than or equal to the
      95th percentile. RESULTS: A total of 251 patients with median age at repair of
      14.6 days met inclusion criteria. Repair was by left thoracotomy in 226 (90%).
      Follow-up data were available for 186 of 251 patients, with median follow-up time
      of 5.4 years (range, 0.2 to 15.3 years); 169 (91%) of these patients underwent
      thoracotomy. There were no early deaths or early reoperations. A proximal
      transverse arch z-score lower than -4.1 or a distal transverse arch z-score of
      less than -2.8 was predictive of repair through sternotomy. Only 4 (2%) patients
      required reintervention (2 patients had balloon angioplasties, 2 had
      reoperations). Transverse arch hypoplasia was a risk factor for reintervention (p
      = 0.048), but surgical approach was not (p = 0.35). Late hypertension was
      identified in only 33 of 186 (18%) patients. CONCLUSIONS: Repair of CoA, even
      with associated transverse arch hypoplasia, by REEEA through left thoracotomy has
      a low mortality, low reintervention rate, and low incidence of late hypertension.

PMID- 30205115
TI  - Genotype-Guided Warfarin Dosing in Patients With Mechanical Valves: A Randomized
      Controlled Trial.
AB  - BACKGROUND: The clinical utility of genotype-guided warfarin dosing remains
      controversial. The objective of this trial was to evaluate the efficacy and
      safety of genotype-guided warfarin dosing in East Asians. METHODS: A double
      blind, randomized control trial was performed to compare a genotype-guided dosing
      algorithm (CYP2C9, VKORC1, and CYP4F2) with a clinical-guided one in the
      initiation treatment for patients with mechanical heart valves. The primary
      outcomes included the time to reach a stable dose and the percentage of time in
      the therapeutic range (TTR). RESULTS: Two hundred one patients were randomly
      assigned to treatment, 101 to control and 100 to study. The major bleeding and
      thromboembolic event-free rate in the study group was 97.0% (95% confidence
      interval: 90.9% to 99.2%). Compared with the control group, the study group
      shortened the time to reach a stable dose (mean: 42.09 +/- 23.655 days versus
      33.52 +/- 20.044 days, p = 0.009). The TTRs were 47.257% and 47.461% in the
      control and study group (p = 0.941), respectively. Patients with the CYP2C9 *1/*3
      genotype had higher international normalized ratio (INR) variability than
      patients with the CYP2C9 *1/*1 genotype (p = 0.024). Compared with normal and
      sensitive responders, the highly sensitive responders were at increased risk of
      an INR of 4.0 or greater (p < 0.05). CONCLUSIONS: The genotype-guided warfarin
      dosing was safe and might be more efficient for the time to reach a stable dose.
      Pharmacogenomic testing might be beneficial to identify the patients with the
      CYP2C9 *1/*3 genotype and the highly sensitive responders, who were in the high
      risk subgroup of patients with mechanical heart valves. An appropriately powered
      study is needed to further confirm these findings.

PMID- 30205116
TI  - Successful Excision of Endobronchial Cellular Schwannoma with Right Lower Sleeve
      Lobectomy.
AB  - Cellular schwannoma is a rare variant of schwannoma showing high cellularity and
      a low mitotic index. A 64-year-old man was admitted to our hospital with a 2
      month history of productive cough. Chest computed tomography showed an
      endobronchial tumor with complete atelectasis of the right lower lobe.
      Bronchoscopy showed an endobronchial tumor occluding the intermediate bronchus
      that was diagnosed as a cellular schwannoma on biopsy and successfully excised
      with a right lower sleeve lobectomy to preserve the middle lobe. The
      postoperative course was uneventful, and the patient remains well, with no sign
      of recurrence at the 7-year follow-up.

PMID- 30205117
TI  - Do Estimates of Treatment Risk Based on Clinical Vignettes Differ by Physician
      Gender?
AB  - BACKGROUND: Clinical vignettes are frequently used as instructional and
      evaluative instruments for physicians. Physicians' gender is a source of
      unconscious bias in treatment recommendations. This study assessed whether
      interpretation of information in clinical vignettes differed by physicians'
      gender as a possible source of unconscious bias. METHODS: Thoracic surgeons and
      physicians in cardiothoracic surgical training were asked to provide estimates of
      major complication rates for lung resection on the basis of anonymized clinical
      vignettes of patients undergoing lung resection. Vignettes were categorized as
      low, average, and high risk by using a sum of Charlson Comorbidity Index
      (possible range, 0 to 37) and a combined physiologic score, EVAD (forced
      expiratory volume in 1 second, diffusing capacity of lung for carbon monoxide,
      age; possible range, 0 to 12); participants were not aware of the risk scores or
      vignette categories. Generalized estimating equation linear regression models
      were fit with risk scores treated as a continuous independent variable. RESULTS:
      A total of 247 physicians (105 practicing surgeons, 142 trainees; 203 men, 44
      women) participated in one or more of the studies. Nearly all (103; 98%) of the
      practicing surgeons rated themselves as competent or expert in lung resection
      compared with 77 (54%) of the trainees (p < 0.001). Participants' complication
      estimates mirrored both vignette risk category and combined risk score. There was
      no significant difference between men and women physicians in their estimates of
      complication rates. CONCLUSIONS: Unconscious bias related to physicians' gender
      is not associated with differential use of information in clinical vignettes. Any
      possible bias may arise from face-to-face interactions with patients. Research
      into physicians' and patients' gender differences during such interactions is
      warranted.

PMID- 30205118
TI  - Comparative proteomic analysis of soluble and surface-enriched proteins from
      Acanthamoeba castellanii trophozoites.
AB  - Acanthamoeba castellanii is a free-living organism widely distributed in the
      environment that may cause disease. This protozoan exists in two forms, an
      infective trophozoite and a dormant cyst. The trophozoites are able to cause
      keratitis and granulomatous amoebic encephalitis in humans. Keratitis is an
      acute, sight threatening infection of cornea with potential to cause permanent
      blindness without prompt treatment. However, the lack of suspicion and the low
      awareness about these amoebae besides of the absence of commercially available
      immunodiagnostic tests may delay an accurate diagnosis. The identification of
      proteins with potential for use in immunodiagnosis may improve the parasite
      detection more quickly and specifically. The amoeba adhesion to the host cell is
      the primary step for infection but there is no full understanding of A.
      castellanii proteins relevant for host invasion or infection. In this study, an
      assessment of soluble and surface-enriched protein fractions expressed by A.
      castellanii trophozoites, based on complementary LC-MS/MS approach using peptides
      from SDS-PAGE excised bands, was performed. Our proteomic analysis allowed
      identification of a total of 503 proteins, of which 308 proteins were exclusively
      identified in the soluble fraction, 119 in surface-enriched fraction and 76 in
      both. In silico analysis of functional classification revealed several proteins
      involved in many biological mechanisms in A. castellanii, including pathogen
      survival and infection of mammalian hosts. The analysis of predicted antigenic
      peptides allowed the identification of proteins with potential for
      immunodiagnostic assays.

PMID- 30205119
TI  - Neuroepigenetics and addictive behaviors: Where do we stand?
AB  - Substance use disorders involve long-term changes in the brain that lead to
      compulsive drug seeking, craving, and a high probability of relapse. Recent
      findings have highlighted the role of epigenetic regulations in controlling
      chromatin access and regulation of gene expression following exposure to drugs of
      abuse. In the present review, we focus on data investigating genome-wide
      epigenetic modifications in the brain of addicted patients or in rodent models
      exposed to drugs of abuse, with a particular focus on DNA methylation and histone
      modifications associated with transcriptional studies. We highlight critical
      factors for epigenomic studies in addiction. We discuss new findings related to
      psychostimulants, alcohol, opiate, nicotine and cannabinoids. We examine the
      possible transmission of these changes across generations. We highlight
      developing tools, specifically those that allow investigation of structural
      reorganization of the chromatin. These have the potential to increase our
      understanding of alteration of chromatin architecture at gene regulatory regions.
      Neuroepigenetic mechanisms involved in addictive behaviors could explain
      persistent phenotypic effects of drugs and, in particular, vulnerability to
      relapse.

PMID- 30205120
TI  - Disappearance of self-serving bias: Reward positivity reflects performance
      monitoring modulated by responsibility attribution in a two-person cooperative
      task.
AB  - Performance monitoring plays a virtual role in individual reinforcement learning.
      However, it remains unclear how responsibility attribution modulates the
      individual monitoring process in a social cooperative context. In the present
      study, 46 participants received feedback on the team's monetary outcome, teammate
      performance, and their own performance sequentially for a two-person task. Using
      event-related potential (ERP), we analyze brain activity in response to
      performance monitoring during team and self feedback, indexed according to reward
      positivity (RewP). Overall, the participants reported a modest tendency towards
      causal attribution in terms of taking more responsibility for negative rather
      than positive team-feedback, thus indicating an opposite pattern to the so-called
      self-serving bias phenomenon. Based on post-experiment responsibility
      attribution, participants were further divided into a 'Modest' group (N = 23) who
      reported more responsibility for team failure than success, and an 'Ordinary'
      group (N = 23) who made comparable attribution irrespective of team outcome. The
      ERP results show that there is no difference in RewP amplitudes between the two
      groups when the participants were processing the team's monetary feedback.
      However, the observed RewP amplitudes are notably different in the Modest group
      when processing self-performance feedback at different levels of responsibility
      attribution. These findings demonstrate that neural activity during performance
      monitoring does not differ between the two groups. However, using different
      responsibility attribution tendencies does affect brain activity during
      individual performance monitoring. The observed RewP effect sheds light on the
      automatic and implicit evaluation of one's own performance in a social
      cooperative context.

PMID- 30205121
TI  - Persistent inflammatory pain alters sexually-motivated behavior in male rats.
AB  - Urine from pro-oestrus female rodents evokes increased levels of sexually
      motivated behaviors in males, including sniffing and scent marking of the urine
      spot as well as activation of brain reward regions. Stressors such as social
      defeat can adversely impact urine scent marking behavior in male rodents, an
      effect that can be mitigated with anti-depressant drugs. Persistent pain is also
      known to be a potent stressor, producing elevated levels of plasma corticosterone
      as well as reduced sucrose preference and reduced social interaction. However,
      the effect of persistent pain on sexually-motivated behavior is unknown. Here, we
      compared urine scent marking behavior in male rats for up to 3 weeks following
      intra-articular injection of Complete Freund's Adjuvant (CFA) or sham injection.
      CFA-injected rats exhibited profound and ongoing deficits in static weight
      bearing capacity. CFA-induced persistent inflammatory pain increased plasma
      corticosterone levels and reduced urine scent marking behavior in male rats.
      Moreover, while the vast majority of injured rats showed decreased urine scent
      marking preference for the pro-oestrus female urine spot, male rats with higher
      baseline scent marking preference also exhibited higher post-injury scent marking
      preference, more sniffing behavior and lower levels of plasma corticosterone,
      compared to those with lower baseline scent marking preference. Overall, scent
      marking behavior may be an ethologically relevant behavioral predictor of
      persistent pain-induced stress in rats, representing a novel translational
      approach to understanding chronic pain comorbidities.

PMID- 30205122
TI  - Debridement, antibiotics and implant retention for periprosthetic joint
      infections: A systematic review and meta-analysis of treatment outcomes.
AB  - OBJECTIVES: We aimed to assess infection control rates after DAIR in patients
      with periprosthetic joint infection (PJI) following joint arthroplasty and
      evaluate factors associated with infection control using a systematic review and
      meta-analysis. METHODS: We searched MEDLINE, EMBASE, Web of Science, Cochrane
      databases and reference lists of relevant studies up to May 2017. Longitudinal
      studies conducted in patients with PJI treated exclusively by DAIR were eligible.
      Infection control rates were meta-analysed using random-effect models after
      arcsine transformation. RESULTS: We included 93 articles based on 99 unique
      observational studies with data on 4897 PJIs treated by DAIR. The infection
      control rate for DAIR ranged from 11.1% to 100% with an overall pooled estimate
      of 61.4% (95% CI, 57.3-65.4) and a 95% prediction interval of 25.5% to 91.8%.
      Infection control rates remained generally similar for several relevant
      characteristics, except for evidence of variation by age, geographical location,
      type of infection and joint affected, duration of parenteral antibiotic therapy
      after the DAIR procedure, and period (year) of DAIR procedure. CONCLUSIONS: The
      DAIR approach remains an option for the treatment of PJI as it is associated with
      acceptable infection control rates, particularly in acute postoperative
      infections and infections of the hip and shoulder joints.

PMID- 30205123
TI  - Influence of total body irradiation dose rate on idiopathic pneumonia syndrome in
      acute leukemia patients undergoing allogeneic hematopoietic cell transplantation.
AB  - PURPOSE/OBJECTIVES: To determine the relationship between dose rate and other
      factors with the development of idiopathic pneumonia syndrome (IPS) in acute
      lymphoblastic (ALL) and acute myeloid (AML) leukemia patients undergoing total
      body irradiation (TBI)-based myeloablative conditioning for allogeneic
      hematopoietic cell transplantation (HCT). MATERIALS/METHODS: From 2006 to 2016,
      202 acute leukemia patients (111 ALL, 91 AML) ranging in age from 1 to 57 years
      (median: 25) underwent allogeneic HCT at XXX. Pre-transplantation conditioning
      included cyclophosphamide (120 mg/kg) with (68%) or without fludarabine (75
      mg/m2) followed by 13.2 Gy TBI given in 8 twice daily fractions of 1.65 Gy over 4
      days. Dose rate varied based on linac availability and ranged from 8.7-19.2
      cGy/min. Patients were stratified by receipt of high (>15 cGy/min) (HDR) (56%) or
      low (<=15 cGy/min) dose rate (LDR) (44%) TBI for all 8 fractions. IPS was defined
      as pulmonary injury based on clinical symptoms, radiographic evidence, and/or
      pulmonary function testing within 100 days of HCT in the absence of concurrent
      infection. RESULTS: IPS developed in 42 (21%) patients between 4 and 73 days
      (median: 16) after transplantation. HDR TBI was associated with a higher rate of
      IPS compared to LDR TBI [29% versus 10%, P<.01]. On multiple regression analysis,
      HDR remained a significant predictor of IPS [HR: 2.6 (95% CI: 1.2-5.3), P=.01)
      and this led to inferior 1-year overall survival (60% versus 76%, P=.01) and
      increased 1-year non-relapse mortality (28% versus 15%, P=.02). CONCLUSIONS: TBI
      dose rates <=15 cGy/min reduce the risk of post-transplantation IPS and improve
      overall survival. LDR TBI should be strongly considered as an easily implemented
      parameter to improve the safety of pre-transplantation TBI-based conditioning.

PMID- 30205125
TI  - Preliminary evaluation of diagnostic accuracy and precision of a competitive
      ELISA for detection of antibodies to Rift Valley fever virus in cattle and sheep
      sera.
AB  - Rift Valley fever virus (RVFV), a mosquito-borne, zoonotic pathogen, is endemic
      to sub-Saharan Africa and has spread beyond the continent to the Arabian
      Peninsula. The high likelihood of RVFV's spread to other non-endemic countries
      spurs the need for development and implementation of rapid diagnostic tests and
      surveillance programs. In this preliminary evaluation, we assessed the diagnostic
      accuracy and precision of a recombinant RVFV nucleoprotein based competitive
      ELISA (cELISA) assay to detect RVFV antibodies compared to a plaque reduction
      neutralization test (PRNT80), using sera of cattle and sheep that were
      experimentally infected with either the MP-12 RVFV vaccine or a wild-type RVFV
      strain, as well as using known RVFV negative sera. With the manufacturer
      recommended 60% inhibition for the cELISA and a 1:40 titer for the PRNT80, the
      sensitivity and specificity of the cELISA assay was determined to be 95.1% (95%
      CI = 83.5-99.4%) and 91.8% (95% CI = 85.0-96.2%), respectively. Antibodies to
      RVFV were first detected at 5 days post inoculation (dpi) in both species' sera.
      The prototype cELISA is an easy to implement, sensitive, specific, and safe test
      for the detection of antibodies to RVFV that can be used in surveillance
      programs.

PMID- 30205124
TI  - Prospective Immunophenotyping of CD8+ T-cells and Associated Clinical Outcomes of
      Patients with Oligometastatic Prostate Cancer Treated with Metastasis-Directed
      SBRT.
AB  - PURPOSE: To study the effects of metastasis-directed stereotactic body radiation
      therapy (mdSBRT) on CD8+ T-cell subpopulations and to correlate post-mdSBRT
      immunophenotypic responses with clinical outcomes in patients with
      oligometastatic prostate cancer (OPCa). METHODS AND MATERIALS: Peripheral blood
      mononuclear cells (PBMCs) were prospectively isolated from 37 patients with OPCa
      (<=3 metastases) treated with mdSBRT. Immunophenotyping identified circulating
      CD8+ T-cell subpopulations including: Tumor-Reactive (TTR), Effector Memory
      (TEM), Central Memory (TCM), Effector (TEF), and Naive (TN) T-cells from samples
      collected before and after mdSBRT. Univariate Cox proportional hazards regression
      was used to assess whether changes in these T-cell subpopulations were potential
      risk factors for death and/or progression. Kaplan-Meier method was used for
      survival. Cumulative incidence for progression and new distant metastasis was
      estimated considering death as a competing risk. RESULTS: Median follow-up was 39
      months (IQR 34-43). Overall survival at 3 years was 78.2%. Cumulative incidence
      for local progression and new distant metastasis at 3 years was 16.5% and 67.6%,
      respectively. Between baseline and day 14 after mdSBRT, an increase in the TCM
      cell subpopulation was associated with the risk of death (HR 1.22 [95%CI, 1.02
      1.47]; P=0.033), and an increase in the TTR cell subpopulation was protective
      against the risk of local progression (HR 0.80 [95%CI, 0.65-0.98]; P=0.032).
      CONCLUSIONS: An increase in the TTR cell subpopulation was protective against the
      risk of disease progression while an increase in the TCM cell subpopulation was
      associated with the risk of death in patients with OPCa treated with mdSBRT.
      Disease control may be further improved by better understanding the CD8+ T-cell
      subpopulations, and by enhancing their anti-tumor effect.

PMID- 30205126
TI  - T cell receptor (TCR) alpha and beta genes of loach (Misgurnus anguillicaudatus):
      Molecular cloning and expression analysis in response to bacterial, parasitic and
      fungal challenges.
AB  - In vertebrates, the T cell receptor (TCR) plays a crucial role in immune system.
      To date, the roles of fish TCRs in response to pathogen infection are still
      poorly understood. In the present study, we firstly cloned and identified the
      TCRalpha and TCRbeta from dojo loach (Misgurnus anguillicaudatus) by RACE
      approaches. The full-length cDNAs of Ma-TCRalpha and Ma-TCRbeta include an open
      reading frame (ORF) of 723 and 879 bp encoding a polypeptide of 241 and 293 amino
      acids, respectively. Structural analysis indicated that Ma-TCRalpha and Ma
      TCRbeta had a signal peptide, IgV domain, IgC domain, a connecting peptide (CPS),
      a transmembrane region (TM) and a cytoplasmic (CYT), which are similar to their
      counterparts described in other teleost. Phylogenetic analysis supported that Ma
      TCR Calpha and Ma-TCR Cbeta were closely related to the Calpha and Cbeta region
      of Cyprinidae family, respectively. Transcriptional expression analysis indicated
      that Ma-TCRalpha and Ma-TCRbeta mRNAs were ubiquitously expressed in a wide array
      of tissues and most abundantly found in skin, brain, kidney, gill and spleen. The
      expression patterns of Ma-TCRalpha and Ma-TCRbeta after bacteria (F. columnare
      G4), parasite (Ichthyophthirius multifiliis) and fungus (Saprolegnia) infection
      were detected by qRT-PCR. Additionally, the morphological changes of gill and
      skin following the three infection models were investigated. The results clearly
      indicated that Ma-TCRalpha and Ma-TCRbeta was significant up-regulated not only
      in spleen and kidney, but also in skin and gill. In summary, our present findings
      suggested that Ma-TCRalpha and Ma-TCRbeta might play significantly roles in the
      modulation of immune response and protect loach from different pathogens
      infection.

PMID- 30205127
TI  - Improved anticancer efficacy of doxorubicin mediated by human-derived cell
      penetrating peptide dNP2.
AB  - Although cell penetrating peptides (CPPs) have been extensively studied as an
      approach to deliver anti-cancer drugs into the tumor cells for the last 30 years,
      no FDA-approved CPP-based drugs are available, implying that the existing CPPs
      may have less efficiency in human or have side effects such as toxicity. Herein,
      we established a tumor targeting drug delivery system by attaching a human
      derived cell-penetrating peptide dNP2 (CKIKKVKKKGRKKIKKVKKKGRK) to N-(2
      hydroxypropyl)-methacrylamide (HPMA) copolymer doxorubicin conjugates. Firstly,
      in vitro cytotoxicity of free dNP2 peptide and dNP2-modified blank HPMA copolymer
      were examined. A classic CPP-R8 (CRRRRRRRR) was chosen for comparison and the
      results showed that 200 MUM free R8 reduced cell viability to 68.4% but dNP2 did
      not induce any toxicity at the same concentration. After conjugation to HPMA
      copolymer, a similar trend was also observed which indicated the excellent
      biocompatibility of dNP2. Next, effect of dNP2 modification on cellular uptake,
      DNA damage, apoptosis and anticancer activity of HPMA copolymer doxorubicin
      conjugates were evaluated. It was excited that dNP2 modified HPMA copolymer (P
      (dNP2)-DOX) not only had a higher uptake by HeLa cell compared with non-modified
      copolymer (P-DOX) but resulted in an enhanced drug distribution in nuclei.
      Furthermore, P-(dNP2)-DOX exhibited greater DNA damage ability (10.5 folds higher
      than P-DOX) in comet assay and induced more apoptosis cells (46.0%). P-(dNP2)-DOX
      also showed a stronger cell cytotoxicity (3-fold to P-DOX) as well as in 3D tumor
      spheroid assay (inhibition rate 78%). All these results suggested that the human
      derived cell-penetrating peptide dNP2 could facilitate tumor nuclear-accumulation
      of anti-cancer drugs and improve anticancer efficacy. More importantly, dNP2 has
      less toxicity compared with classic CPP-R8 thus shows the potential for the
      clinic cancer therapy.

PMID- 30205128
TI  - Personalized orodispersible films by hot melt ram extrusion 3D printing.
AB  - This work demonstrates the feasibility of the extemporaneous preparation of
      maltodextrins orodispersible films (ODF) by hot-melt ram-extrusion 3D printing.
      This method consists of three simple technological operations which can be also
      implemented in a pharmacy setting. First, maltodextrins, drug, and other
      excipients are mixed in a mortar and wetted with the plasticizer (i.e.
      glycerine). Then, the mixture is fed in the chamber of the ram-extruder and
      heated. ODF are individually printed on the packaging material foil and sealed
      without further manipulations. The critical formulation attributes and process
      variables were investigated to define the processability space. In particular,
      the optimal conditions to print a mixture of maltodextrins/glycerine in a 80/20
      w/w ratio resulted: heating temperature: 85  degrees C; needle gauge: 18 G;
      needle-packaging material foil distance: 0.6 mm; maximum print rate: 50 mm/s;
      filling angle: 120 degrees . The maximum drug loading was about 40%, when
      paracetamol was used as model drug. The compounded ODF complied with USP and Ph.
      Eur. specifications for disintegration time (<1 min). The dissolution pattern of
      paracetamol overlapped with that obtained from ODF with a similar composition
      prepared by the consolidated solvent casting technique, demonstrating the
      suitability of the proposed technology.

PMID- 30205129
TI  - An analysis of retractions of dental publications.
AB  - OBJECTIVES: To comprehensively report on the characteristics of retracted
      publications in the field of dentistry. METHODS: We searched MEDLINE (via
      PubMed), PubMed Central, Web of Science and Google Scholar databases for dental
      retracted articles from database inception to 02 July 2018. In addition, we
      scanned the search engine Google Scholar, and the website, Retraction Watch
      (www.retractionwatch.com), for retracted dental articles. Two researchers
      independently screened titles, abstracts and full text of search results.
      Descriptive data was collected on each retracted article including reason for
      retraction, study type, journal impact factor, and time between publication and
      retraction. Regression models were used to evaluate the association between
      journal impact factor and retraction characteristics. RESULTS: A total of 138
      retractions of dental articles were included. Reasons for retraction were
      misconduct (N = 100, 72.5%), with the most frequently reported misconduct being
      overlap/plagiarism and innacurate/falsified conducting and reporting (N = 53,
      38.4%). In vitro (N = 39, 28.3%), case reports (N = 29, 21%) and narrative
      reviews (N = 19, 13.8%) were study design most frequently identified in retracted
      articles. The median time between article publication and date of retraction
      notice was 1 year (interquartile-range [IQR] = 0-2 years). More than half of the
      retracted articles (n = 82, 59.4%) were cited post-retraction. A retracted
      article reporting a randomized controlled trial was more likely to appear in
      journal with higher impact factor than a retracted case report (mean difference
      [MD] = 2.2; 95% confidence interval [CI] = 1.2,3.1. Articles retracted after 2012
      were likely to appear in journals with a lower impact factor (MD=-1.3; 95%CI=
      1.8, 0.8). CONCLUSIONS: Research misconduct is the main reason for retraction of
      dental articles. A substantial proportion of these articles were still being
      cited after their retraction. CLINICAL SIGNIFICANCE: This report of dental
      retraction articles informs that more transparency is needed with data reporting
      in dentistry to improve writing practices in dentistry. A more complete report of
      retractions and their causes would provide more accurate information to inform
      researchers and editors to avoid or reduce future cases of retractions. More
      complete and accurate reporting would increase the overall trust in dental
      research.

PMID- 30205131
TI  - Response to the Letter to the Editor entitled, "Use of immortal time within
      survival analysis": JAAD-D-18-01157.

PMID- 30205130
TI  - Contingent negative variation in acute trauma patients: A prospective exploratory
      study.
AB  - It is still unclear why some individuals completely recover after an acute trauma
      and others develop a long-lasting post-traumatic stress disorder (PTSD). This
      study investigates whether the contingent negative variation (CNV) - a slow
      negative event-related potential - may be associated with the occurrence of PTSD
      after acute trauma. CNV (auditory 2-stimulus reaction time paradigm) was recorded
      within one month as well as 6 months after an acute trauma (dangerous or grave
      physical injuries, witnessing of attempted suicide or murder, robbery, extortion,
      accidents, heavy illness, death or loss of an important person, hostage-taking)
      in 39 otherwise healthy adults and compared with CNV recordings in 38 healthy
      control subjects without potentially traumatizing experience in their history.
      According to their subsequent clinical course, these subjects were divided into
      two groups: participants who recovered completely 1 month after the trauma (PTSD-
      group, n = 31), and those who began to experience PTSD (PTSD+ group, n = 8).
      Patients from both trauma groups were characterized by a significantly longer
      reaction time immediately after the trauma. The PTSD+ group demonstrated lower
      amplitudes of the late CNV component immediately and six months after the trauma
      compared with the PTSD- and the control group. Whether the lower CNV amplitudes
      in patients who develop PTSD after the acute trauma, which is already present in
      the first days after the trauma, may be related to a higher risk for development
      of PTSD in these subjects, this has to be clarified in further prospective
      studies.

PMID- 30205132
TI  - Antibiotic exposure is associated with cutaneous adverse events in hairy cell
      leukemia patients treated with purine analogs.

PMID- 30205133
TI  - Recurrent fevers, progressive lipodystrophy and annular plaques in a child.

PMID- 30205135
TI  - Kahweol inhibits proliferation and induces apoptosis by suppressing fatty acid
      synthase in HER2-overexpressing cancer cells.
AB  - Kahweol is a coffee-specific diterpene found in the beans of Coffea arabica and
      has been reported to demonstrate various biological activities, including anti
      inflammatory, antioxidant, and apoptotic properties. In the present study, we
      examined the molecular mechanism of kahweol in human epidermal growth factor
      receptor-2 (HER2)-overexpressing breast cancer cells. Kahweol preferentially
      inhibited cell proliferation and induced cell death through the induction of a
      caspase 3-dependent pathway in HER2-overexpression breast cancer cell lines.
      Kahweol treatment substantially reduced the levels of HER2 protein, mRNA, and
      transcriptional activity in SKBR3 cells. Kahweol exerts its potent anticancer
      efficacy by the upregulation of polyomavirus enhancer activator 3 (PEA3) and
      downregulation of activator protein 2 (AP-2) to inhibit aberrantly activated HER2
      signaling. Fatty acid synthase (FASN) expression and sterol regulatory element
      binding protein-1c (SREBP-1c) activity were downregulated by kahweol. In
      addition, kahweol lowered the levels of phosphorylated Akt and its downstream
      targets mammalian target of rapamycin (mTOR) and cyclin D1. Furthermore, we found
      that blocking Akt signaling through kahweol treatment significantly reduced FASN
      expression and subsequently suppressed cell proliferation in HER2-overexpressing
      cancer cells. Overall, this study suggests that kahweol could be a useful
      adjuvant therapeutic agent in the treatment of HER2-overexpressing breast cancer.

PMID- 30205136
TI  - Development of a curated Hershberger database.
AB  - A systematic literature review was conducted to identify Hershberger bioassays
      for ~3200 chemicals including those used to validate the OECD/US EPA guideline
      assay, US EPA's chemicals screened for endocrine activity, and the library of
      chemicals run in US EPA 's ToxCast in vitro assays. For 134 chemicals that met
      pre-defined criteria, experimental results were extracted into a database used to
      characterize uncertainty in results and evaluate the concordance of the
      Hershberger assay with other in vivo rodent studies that measure androgen
      responsive endpoints. Of 25 chemicals tested in >1 Hershberger study, 28% had
      disagreements between studies (i.e. >=1 positive and >=1 negative study), and of
      the 65 chemicals tested in Hershberger studies and other in vivo studies with
      androgen-responsive endpoints, 43% indicated disagreements, though in some cases
      these may be explained by differences in study designs or physiology of the
      animal model. Ultimately, 49 chemicals were identified with reproducible androgen
      pathway responses confirmed in >=2 in vivo rodent studies that could be
      considered reference chemicals useful for validating alternative methods.

PMID- 30205137
TI  - Evaluation of androgen assay results using a curated Hershberger database.
AB  - A set of 39 reference chemicals with reproducible androgen pathway effects in
      vivo, identified in the companion manuscript [1], were used to interrogate the
      performance of the ToxCast/Tox 21 androgen receptor (AR) model based on 11 high
      throughput assays. Cytotoxicity data and specificity confirmation assays were
      used to distinguish assay loss-of-function from true antagonistic signaling
      suppression. Overall agreement was 66% (19/29), with ten additional inconclusive
      chemicals. Most discrepancies were explained using in vitro to in vivo
      extrapolation to estimate equivalent administered doses. The AR model had 100%
      positive predictive value for the in vivo response, i.e. there were no false
      positives, and chemicals with conclusive AR model results (agonist or antagonist)
      were consistently positive in vivo. Considering the lack of reproducibility of
      the in vivo Hershberger assay, the in vitro AR model may better predict specific
      AR interaction and can rapidly and cost-effectively screen thousands of chemicals
      without using animals.

PMID- 30205134
TI  - Permethrin, a pyrethroid insecticide, regulates ERK1/2 activation through
      membrane depolarization-mediated pathway in HepG2 hepatocytes.
AB  - Permethrin is a pyrethroid insecticide that acts thru membrane depolarization and
      is known to disrupt calcium levels in neurons. Disrupted calcium homeostasis is
      linked to oxidative stress as well as many other cellular mis-functions and
      permethrin has been reported to disrupt lipid and glucose metabolism in animals
      and mammalian cell models. It is not known, however, if permethrin influences
      calcium levels and its associated cellular mechanisms in liver cells. Thus, the
      goal of the current study was to investigate the mechanisms of permethrin on
      calcium-mediated cellular signaling pathway, particularly on activation of
      extracellular signal-related kinase (ERK1/2 or p42/p44) using human hepatocytes,
      HepG2. The current results showed that permethrin treatment induced oxidative
      stress and phosphorylation of ERK1/2, which were dependent upon voltage-sensitive
      sodium channels (VSSC). It was further determined that permethrin-induced ERK1/2
      activation was mediated by the metabotropic glutamate receptors (mGluRs)
      phosphoinositide phospholipase C (PLC)-protein kinase C (PKC) pathway, but not by
      changes of intracellular calcium or ER stress-mediated mechanisms.

PMID- 30205138
TI  - Cashew apple bagasse as new feedstock for the hydrogen production using dark
      fermentation process.
AB  - Cashew apple bagasse (CAB) has been studied as feedstock for the biohydrogen
      production using Clostridium roseum and the dark fermentation process.
      Pretreatment with alkaline hydrogen peroxide (CAB-AHP) on raw material and the
      acid and enzymatic hydrolysis have been taken into account to evaluate the H2
      yields. Results show that the acid hydrolysate obtained from CAB produced higher
      H2 molar yield (HMY) (15 mmolH2/Lhydrolysate) than the acid hydrolysate from CAB
      AHP (4.99 mmolH2/Lhydrolysate), These HMY were noticeably higher than values
      obtained from the enzymatic hydrolysate of CAB-AHP (1.05 mmolH2/Lhydrolysa) and
      the enzymatic hydrolysate of CAB (0.59 mmolH2/Lhydrolysa). The maximum
      biohydrogen productivity (12.57 mLH2/L.h) was achieved using the acid hydrolysate
      from CAB, with a H2 content of about 72% vol, that could be satisfactory in view
      of an energetic applications of the biogas. Results suggest that CAB could be
      considered for the hydrogen production process, providing an appropriate
      destination for this lignocellulosic biomass, and consequently, reducing the
      environmental impact it can exert.

PMID- 30205139
TI  - Epigenetic modulation of metabolism in glioblastoma.
AB  - Epigenetic and metabolic alterations incancer cells are highly associated.
      Glioblastoma multiforme (GBM) is a complicated pathological process with
      dysregulated methylation and histone modifications. Metabolic modulation of
      epigenetics in gliomas was previously summarized. However, epigenetic modulation
      is also important in metabolic decision. Recently, there has been a tremendous
      increase in understanding of DNA methylation, chromatin modulation, and non
      coding RNAs in the regulation of cell metabolism, especially glycolytic
      metabolism in GBM. In this review, we summarize DNA methylation, histone
      alteration, and non-coding RNA mediated epigenetic modulation of metabolism in
      GBM and discuss the future research directions in this area and its applications
      in GBM treatment.

PMID- 30205141
TI  - Classification of riboswitch sequences using k-mer frequencies.
AB  - Riboswitches are non-coding RNAs that regulate gene expression by altering the
      structural conformation of mRNA transcripts. Their regulation mechanism might be
      exploited for interesting biomedical applications such as drug targets and
      biosensors. A major challenge consists in accurately identifying metabolite
      binding RNA switches which are structurally complex and diverse. In this regard,
      we investigated the classification of 16 riboswitch families using supervised
      learning algorithms trained solely with sequence-based features. We generated a
      reduced feature set and proposed a visual representation to explore its
      components. We induced Support Vector Machine, Random Forest, Naive Bayes, J48,
      and HyperPipes classifiers with our proposed feature set and tested their
      performance over independent data. Our best multi-class classifier achieved F
      measure values of 0.996 and 0.966 in the training and test phases, respectively,
      outperforming those of a previous approach. When compared against BLAST, our best
      classifiers yielded competitive results. This work shows that the classifiers
      trained with our sequence-based feature set accurately discriminate riboswitches.

PMID- 30205143
TI  - A cross-educational approach on skill-related movement technique performance:
      Central neuronal motor behaviour preceding the short badminton backhand serve.
AB  - Training in a particular sport not only leads to a higher accuracy in movement,
      it also creates neuronal modulations in different areas of the brain.
      Electroencephalography (EEG) has been on the rise to detect these neuronal
      modulations to address applied research approaches in sports-specific setups with
      focus on movement-related cortical potentials (MRCP) especially the readiness
      potential (RP). While many studies considered the RP in laboratory settings using
      button pressing, there is little research on sport-specific movements performed
      in realistic setups. Therefore the aim of this study was to examine the short
      backhand serve of expert and novice badminton players. 16 healthy, right-handed
      men participated in this study, eight experts and eight novices. A surface EMG
      was recorded from limb muscles and simultaneous EEG was recorded. RP peak
      increased significantly (p < 0.05) in expert compared to novices when serving
      with the dominant hand. RP onsets revealed no significant changes (p = 0.70). In
      line with previous reports, this study pointed out that complex movements such as
      the short badminton backhand serve produces higher RP peaks when performed
      precisely, indicating for long lasting practice and level of experience.

PMID- 30205140
TI  - Treatment duration affects cytoprotective efficacy of positive allosteric
      modulation of alpha7 nAChRs after focal ischemia in rats.
AB  - To minimize irreversible brain injury after acute ischemic stroke (AIS), the time
      to treatment (i.e., treatment delay) should be minimized. However, thus far, all
      cytoprotective clinical trials have failed. Analysis of literature identified
      short treatment durations (<=72 h) as a common motif among completed
      cytoprotective clinical trials. Here, we argue that short cytoprotective regimens
      even if given early after AIS may only slow down the evolution of ischemic brain
      injury and fail to deliver sustained long-term solutions leading to relapses that
      may be misinterpreted for conceptual failure of cytoprotection. In this
      randomized blinded study, we used young adult male rats subjected to transient 90
      min suture middle cerebral artery occlusion (MCAO) and treated with acute vs. sub
      chronic regimens of PNU120596, a prototypical positive allosteric modulator of
      alpha7 nicotinic acetylcholine receptors with anti-inflammatory cytoprotective
      properties to test the hypothesis that insufficient treatment durations may
      reduce therapeutic benefits of otherwise efficacious cytoprotectants after AIS. A
      single acute treatment 90 min after MCAO significantly reduced brain injury and
      neurological deficits 24 h later, but these effects vanished 72 h after MCAO.
      These relapses were avoided by utilizing sub-chronic treatments. Thus, extending
      treatment duration augments therapeutic efficacy of PNU120596 after MCAO.
      Furthermore, sub-chronic treatments could offset the negative effects of
      prolonged treatment delays in cases where the acute treatment window after MCAO
      was left unexploited. We conclude that a combination of short treatment delays
      and prolonged treatment durations may be required to maximize therapeutic effects
      of PNU120596, reduce relapses and ensure sustained therapeutic efficacy after
      AIS. Similar concepts may hold for other cytoprotectants including those that
      failed in clinical trials.

PMID- 30205145
TI  - Acute Type A Aortic Dissection: Managing More Than Just the Entry-Tear.
AB  - As emergency repair for acute type A aortic dissection is improving, the
      reintervention rate increases. Over 10% of cases require an aortic
      reintervention, which should ideally be performed in an early stage to allow for
      positive aortic remodeling and to prevent limitations by the stiffened aortic
      flap. These reinterventions remain a surgical challenge and may come with
      complications. We provide a comprehensive overview of different management
      strategies and their success in treating aortic adverse remodelling, based on
      current evidence of the literature. Two meta-analyses and an additional
      literature search yielded comparable mortality rates between limited repair and
      extensive repair. Cardiopulmonary bypass time, cross clamping time and cardiac
      arrest time were significantly shorter in limited repairs. Reintervention rate
      was generally lower in extensive repair, although not always significant. In
      conclusion, the early aggressive approach may be useful to lower reintervention
      rates. However, it has not yet been proven to be more beneficial. It will be
      imperative to develop a patient-specific early stage prediction model for
      residual aortic reintervention.

PMID- 30205142
TI  - Co-activation of both 5-HT1A and 5-HT7 receptors induced attenuation of
      glutamatergic synaptic transmission in the rat visual cortex.
AB  - It has been suggested that functional interactions between the 5-HT receptor
      subtypes may modulate glutamatergic synaptic transmission. In this study, we used
      whole-cell patch-clamp recordings to test the role of 5-HT receptors in mediating
      the AMPA receptor-mediated miniature excitatory postsynaptic currents (mEPSCs) in
      layer II/III pyramidal neurons of the rat visual cortex. We found that the AMPA
      receptor-mediated component of mEPSCs could be inhibited by exogenously applied 5
      HT. 5-HT significantly reduced the glutamatergic mEPSC amplitude and increased
      the inter-event interval of glutamatergic mEPSCs. Bath application of 5-CT or 8
      OH-DPAT (the 5-HT1A and 5-HT7 receptor agonist) mimicked 5-HT in its effect on
      mEPSCs. Additionally, a selective antagonist for the 5-HT7 receptor, SB-269970,
      displayed no influence on the inhibition of glutamatergic synaptic transmission
      by 5-CT or 8-OH-DPAT. Similar results were obtained by exogenously applied WAY
      100135, the selective 5-HT1A receptor antagonist. However, the inhibition of
      glutamatergic synaptic transmission by 5-CT or 8-OH-DPAT was completely blocked
      by co-application of WAY-100135 and SB-269970. Altogether, our results indicated
      that 5-HT suppressed glutamatergic synaptic transmission by co-activation of
      synaptic 5-HT1A receptors and 5-HT7 receptors in layer II/III pyramidal neurons
      of the rat visual cortex.

PMID- 30205147
TI  - Old Dog, New Tricks.

PMID- 30205146
TI  - Neoaortic Root Incorporation of Anomalous Left Coronary Artery From Pulmonary
      Artery in Hypoplastic Left Heart Syndrome: An Alternative Technique.

PMID- 30205144
TI  - Surgery for Tumors of the Heart.
AB  - Most surgeons will encounter only a handful of primary cardiac tumors outside of
      myxomas. Approximately 3 quarters of primary cardiac tumors are benign and 1
      quarter is malignant. In most cases, cardiac tumors are silent but when symptoms
      do occur, they are primarily determined by tumor size and anatomical location,
      not by histopathology. The diagnosis and preoperative imaging relies heavily on
      multimodal imaging including echocardiography, computed tomography, magnetic
      resonance imaging, and coronary angiography. Surgical resection is the most
      common treatment for most simple primary cardiac tumors and for some complex
      benign tumors. Surgical resection of primary cardiac tumors frequently involves
      the need for complex cardiac reconstruction, particularly when malignant.
      Secondary tumors to the heart are 30 times more frequent than primary cardiac
      tumors, and their incidence is increasing, largely as a result of advances in
      cancer diagnosis and therapy. Surgical resection is feasible in only a small
      fraction of highly-selected patients with secondary tumors to the heart. For
      complex benign tumors-such as paraganglioma or large fibromas-and all primary and
      secondary malignant tumors, a multidisciplinary cardiac tumor team review in
      experienced centers of excellence is recommended.

PMID- 30205148
TI  - A review of interventions against fetal alcohol spectrum disorder targeting
      oxidative stress.
AB  - INTRODUCTION: Fetal alcohol spectrum disorder is caused by maternal ethanol
      exposure; it causes physical, behavioral, cognitive, and neural impairments
      (Murawski et al., 2015). Mechanisms of FASD causing damage are not yet fully
      elucidated. Oxidative stress might be one of its mechanisms (Henderson et al.,
      1995). Yet no effective treatment against FASD has been found other than ethanol
      abstention (Long et al., 2010). METHODS: This review summarizes relevant
      literatures regarding interventions targeting oxidative stress that may relieve
      fetal alcohol spectrum disorder. RESULTS: Astaxanthin was found to mitigate
      embryonic growth retardation induced by prenatal ethanol treatment through
      ameliorating the down regulation of hydrogen peroxide (H2O2) and malondialdehyde
      (MDA) caused by alcohol in a mice model (Zheng et al., 2014; Vabulas et al.,
      2002). Vitamin E protected against fatal alchol spectrum disorders by
      ameliorating oxidative stress in rat models (Mitchell et al., 1999a), and yielded
      a better outcome when it was combined with Vitamin C (Packer et al., 1979; Peng
      et al., 2005). Vitamin C mitigated embryonic retardation caused by alcohol and
      reversed ethanol induced NF-kappaB activation and ROS (reactive oxygen species)
      formation in a Xenopus laevis model (Peng et al., 2005). Beta carotene supplement
      was proved to protect against neurotoxicity in hippocampal cultures of embryos
      induced by alcohol in a rats model (Mitchell et al., 1999a). Prenatal folic acid
      supplement reversed the decrease of body weight caused by maternal ethanol
      treatment and ameliorated the increment of glutathione reductase specific
      activities as well as the increase of thiobarbituric acid reactive substances
      (TBARS) induced by alcohol in a rats model (Cano et al., 2001). Omega-3 fatty
      acids reversed the decrease of reduced glutathione (GSH) levels in brain caused
      by prenatal ethanol treatment in a rats model (Patten et al., 2013). EUK-134
      treatment reduced the incidence of forelimb defects caused by ethanol treatment
      in a mice model (Chen et al., 2004). Pretreatment of activity-dependent
      neurotrophic factor-9 (ADNF-9) and NAPVSIPQ (NAP) protected against prenatal
      ethanol induced fetal death as well as fetal growth abnormalities in a mice
      model, and such treatment reversed the decrease of the rate of reduced
      glutathione (GSH)/ oxidative glutathione (GSSG) caused by alcohol (Spong et al.,
      2001). CONCLUSION: By now interventions against fetal alcohol spectrum disorder
      targeting oxidative stress includes astaxanthin, Ascorbic acid (Vitamin C),
      Vitamin E, beta-carotene, (-)-Epigallocatechin-3-gallate (EGCG), Omega-3 fatty
      acids, etc (see Fig. 1). However, most interventions are only assayed in animal
      models, more clinical trials are needed to show whether antioxidants make an
      effort against FASD damage.

PMID- 30205149
TI  - Silencing of sucrose hydrolase causes nymph mortality and disturbs adult osmotic
      homeostasis in Diaphorina citri (Hemiptera: Liviidae).
AB  - Plant piercing sucking insects mainly feed on phloem sap containing a high amount
      of sucrose. To enhance the absorption of sucrose from the midgut, sucrose
      hydrolase digests sucrose into glucose and fructose. In this study, a sucrose
      hydrolase homolog (DcSuh) was identified and targeted in Diaphorina citri, the
      vector of huanglongbing (HLB), by RNA interference (RNAi). In silico analysis
      revealed the presence of an Aamy domain in the DcSUH protein, which is
      characteristic of the glycoside hydrolase family 13 (GH13). Phylogenetic analysis
      showed DcSuh was closely related to the sucrose hydrolase of other Hemiptera
      members. The highest gene expression levels of DcSuh was found in the 4th and 5th
      instar nymphs. dsRNA-mediated RNAi of DcSuh was achieved through topical feeding.
      Our results showed that application of 0.2 MUL of 500 ng MUL-1 (100 ng) dsRNA
      DcSuh was sufficient to repress the expression of the targeted gene and cause
      nymph mortality and reduce adult lifespan. The reduction in gene expression,
      mortality, and lifespan was dose-dependent. In agreement with the gene expression
      results, treatment with dsRNA-DcSuh significantly reduced sucrose hydrolase
      activity in treated nymphs and emerged adults from treated nymphs. Interestingly,
      some emerged adults from treated nymphs showed a swollen abdomen phenotype,
      indicating that these insects were under osmotic stress. Although the percentage
      of swollen abdomens was low, their incidence was significantly correlated with
      the concentration of applied dsRNA-DcSuh. Metabolomic analyses using GC-MS showed
      an accumulation of sucrose and a reduction in fructose, glucose and trehalose in
      treated nymphs, confirming the inhibition of sucrose hydrolase activity.
      Additionally, most of the secondary metabolites were reduced in the treated
      nymphs, indicating a reduction in the biological activities in D. citri and that
      they are under stress. Our findings indicate that sucrose hydrolase might be a
      potential target for effective RNAi control of D. citri.

PMID- 30205150
TI  - Juvenile hormone promotes locust fat body cell polyploidization and
      vitellogenesis by activating the transcription of Cdk6 and E2f1.
AB  - Juvenile hormone (JH) is known to promote cell polyploidization for insect
      vitellogenesis and egg production, but the underlying mechanisms remain poorly
      understood. Using the migratory locust Locusta migratoria as a model system, we
      report here that the expression of cyclin-dependent kinase 6 (Cdk6) and
      adenovirus E2 factor-1 (E2f1), the core mediators in cell cycle progression is
      regulated by JH and its receptor Methoprene-tolerant (Met). JH acts through its
      receptor complex comprised of Met and Taiman to directly activate the
      transcription of Cdk6 and E2f1. Depletion of Cdk6 or E2f1 results in
      significantly decreased ploidy, precocious mitotic entry and increased cell
      numbers in the fat body, accompanied by substantial reduction of Vitellogenin
      gene expression, blocked ovarian growth and arrested oocyte maturation. These
      findings indicate a crucial role of Cdk6 and E2f1 in JH-regulated
      polyploidization and vitellogenesis as well as a novel regulatory machinery for
      endocycling in insects.

PMID- 30205151
TI  - Acrolein induces NLRP3 inflammasome-mediated pyroptosis and suppresses migration
      via ROS-dependent autophagy in vascular endothelial cells.
AB  - Acrolein is a common environmental pollutant that has been linked to
      cardiovascular diseases, such as atherosclerosis (AS). Increasing evidence
      demonstrates that acrolein impairs the cardiovascular system by targeting
      vascular endothelial cells, but the underlying mechanisms haven't been completely
      elucidated. In human umbilical vein endothelial cells (HUVECs), we observed that
      acrolein treatment induced cell reactive oxygen species (ROS) generation,
      autophagy, pyroptosis and reduced cell migration. In addition, exposure to
      acrolein resulted in NLRP3 inflammasome activation as evidenced by cleavage of
      caspase-1 and downstream mature interleukin (IL)-1beta and IL-18 secretion.
      Knockdown of NLRP3 by small interfering RNA remarkably suppressed acrolein
      induced pyroptosis and increased cell migration. Moreover, the scavenging ROS
      relieved the autophagy, NLRP3 inflammasome activation and pyroptosis.
      Furthermore, the role of autophagy in the acrolein-medicated pyroptosis and cell
      migration was investigated. In our study, 3-methyladenine (3-MA), an autophagy
      inhibitor, aggravated NLRP3 inflammasome activation, pyroptosis and decreased
      cell migration, rapamycin (Rapa), an autophagy inducer, alleviated aforementioned
      phenomenon under acrolein stress. Besides, we found damaged mitochondrion
      accentuated NLRP3 inflammasome and pyroptosis in acrolein-treated cells. In
      conclusion, it is possible that acrolein induced cell pyroptosis and suppressed
      cell migration via ROS-dependent autophagy. What's more, NLRP3 inflammasome
      activation plays a key role in this process.

PMID- 30205153
TI  - The application of caprylic acid in downstream processing of monoclonal
      antibodies.
AB  - Caprylic acid (CA), a naturally occurring eight-carbon fatty acid, has long been
      used as albumin stabilizer, non-IgG fraction precipitant and bactericidal agent
      in pharmaceutical industry. The mechanisms through which CA achieves its effects
      have been correlated with the molecule's protein/lipid binding capacity conferred
      by its octyl moiety. This article, following an initial review of CA's historical
      applications, introduces CA's relatively new application in downstream processing
      of monoclonal antibodies (mAbs). By taking advantage of CA mediated impurity
      precipitation and virus inactivation, it might be possible to develop a two
      column purification process in replacement of the standard three-column process
      without compromising product quality.

PMID- 30205152
TI  - LGK974, a PORCUPINE inhibitor, mitigates cytotoxicity in an in vitro model of
      Parkinson's disease by interfering with the WNT/beta-CATENIN pathway.
AB  - Paraquat (PQ) as an herbicide has been demonstrated to impair dopaminergic
      (DAergic) neurons and highly correlate with the etiology of Parkinson's disease
      (PD). WNT/beta-CATENIN signaling is known for the specification and neurogenesis
      of midbrain DAergic neurons and implicated as a therapeutic target in treating
      many diseases, such as cancer and degenerative diseases. LGK974, a WNT pathway
      inhibitor, is currently under clinical trial for patients with malignancies.
      Since the exact role of WNT/beta-CATENIN signaling in mediating PD is
      undetermined, LGK974 was used to examine its effect on the PQ-induced cell model
      of PD. LGK974 attenuated PQ-induced apoptosis and released mitochondrial pro
      poptotic molecules in human neuroblastoma SH-SY5Y cell. PQ increased the levels
      of beta-CATENIN, non-phosphorylated (Ser33/37/Thr41) beta-CATENIN, and
      phosphorylated glycogen synthase kinase (GSK)-3alpha/beta. PQ also increased the
      nuclear translocation of beta-CATENIN, which can be attenuated by LKG974.
      Furthermore, LGK974 attenuated the PQ-induced release of mitochondrial
      proapoptotic factors and WNT agonist 1-induced cell death. Taken together, we
      have shown for the first time that LGK974 mediated through the WNT/beta-CATENIN
      pathway to prevent PQ-induced cell death.

PMID- 30205154
TI  - cDNA cloning, heterologous expression, protein folding and immunogenic properties
      of a phospholipase A2 from Bothrops ammodytoides venom.
AB  - A mRNA transcript that codes for a phospholipase (PLA2) was isolated from a
      single venom gland of the Bothrops ammodytoides viper. The PLA2 transcript was
      cloned onto a pCR(r)2.1-TOPO vector and subsequently expressed heterologously in
      the E. coli strain M15, using the pQE30 vector. The recombinant phospholipase was
      named rBamPLA2_1, and is composed of an N-terminal fusion protein of 16 residues,
      along with 122 residues from the mature protein that includes 14 cysteines that
      form 7 disulfide bonds. Following bacterial expression, rBamPLA2_1 was obtained
      from inclusion bodies and extracted using a chaotropic agent. rBamPLA2_1 had an
      experimental molecular mass of 15,692.5 Da that concurred with its theoretical
      molecular mass. rBamPLA2_1 was refolded in in vitro conditions and after
      refolding, three main protein fractions with similar molecular masses, were
      identified. Although, the three fractions were considered to represent different
      oxidized cystine isoforms, their secondary structures were comparable. All three
      recombinant isoforms were active on egg-yolk phospholipid and recognized similar
      cell membrane phospholipids to be native PLA2s, isolated from B. ammodytoides
      venom. A mixture of the three rBamPLA2_1 cystine isoforms was used to immunize a
      horse in order to produce serum antibodies (anti-rBamPLA2_1), which partially
      inhibited the indirect hemolytic activity of B. ammodytoides venom. Although,
      anti-rBamPLA2_1 antibodies were not able to recognize crotoxin, a PLA2 from the
      venom of a related but different viper genus, Crotalus durissus terrificus, they
      recognized PLA2s in other venoms from regional species of Bothrops.

PMID- 30205155
TI  - The characterization of androstenone transport in boar plasma.
AB  - The transport of steroids by plasma proteins influences the amount of steroid
      available for uptake by the target tissue. In the boar, androstenone is
      transported to the adipose tissue where it accumulates to cause an off-odour or
      off-flavour in pork, known as boar taint. The mechanism of the transport of
      androstenone in the boar remains unclear, and the plasma protein responsible for
      binding androstenone has yet to be identified. Therefore, the purpose of the
      present study was to characterize the binding of androstenone to plasma proteins
      in the boar. The binding specificity of androstenone to plasma proteins was first
      investigated using a HPLC gel filtration method. [3H]-androstenone was incubated
      with plasma in the presence or absence of unlabeled competitors and the
      displacement of androstenone from plasma proteins was measured. In the presence
      of excess unlabeled competitors, [3H]-androstenone was only partially displaced
      from plasma proteins, indicating it binds to a low affinity high capacity plasma
      protein. Binding kinetics studies were also conducted to characterize the binding
      of androstenone and dehydroepiandrosterone (DHEA) to plasma proteins. The Bmax of
      androstenone and DHEA was approximately the same (89.1% and 92.3%, respectively).
      However, the binding affinity (K) of androstenone was 6.5 fold greater than DHEA
      (0.39 nmol/ml and 0.06 nmol/ml, respectively). Affinity chromatography was used
      to remove albumin from the plasma proteins. Following incubations with
      androstenone and DHEA, the binding observed in the albumin free protein fraction
      was reduced 2.6 and 2.1 fold, respectively relative to the binding in the albumin
      protein fractions. These results provide direct evidence that androstenone is
      transported non-specifically by albumin in the plasma of the boar.

PMID- 30205156
TI  - The serum vitamin D metabolome: What we know and what is still to discover.
AB  - Vitamin D, referring to the two forms, D2 from the diet and D3 primarily derived
      from phototransformation in the skin, is a prohormone important in human health.
      The most hormonally active form, 1alpha,25-dihydroxyvitamin D (1alpha,25(OH)2D),
      formed from vitamin D via 25-hydroxyvitamin D (25(OH)D), is not only important
      for regulating calcium metabolism, but has many pleiotropic effects including
      regulation of the immune system and has anti-cancer properties. The major
      circulating form of vitamin D is 25(OH)D and both D2 and D3 forms are routinely
      measured by LC/MS/MS to assess vitamin D status, due to their relatively long
      half-lives and much higher concentrations compared to 1alpha,25(OH)2D.
      Inactivation of both 25(OH)D and 1alpha,25(OH)2D is catalyzed by CYP24A1 and 25
      hydroxyvitamin D3 3-epimerase. Initial products from these enzymes acting on
      25(OH)D3 are 24R,25(OH)2D3 and 3-epi-25(OH)D3, respectively, and both of these
      can also be measured routinely in some clinical laboratories to further document
      vitamin D status. With advances in LC/MS/MS and its increased availability, and
      with the help of studies with recombinant vitamin D-metabolizing enzymes, many
      other vitamin D metabolites have now been detected and in some cases quantitated,
      in human serum. CYP11A1 which catalyzes the first step in steroidogenesis, has
      been found to also act on vitamins D3 and D2 hydroxylating both at C20, but with
      some secondary metabolites produced by subsequent hydroxylations at other
      positions on the side chain. The major vitamin D3 metabolite, 20S-hydroxyvitamin
      D3 (20S(OH)D3), shows biological activity, often similar to 1alpha,25(OH)2D3 but
      without calcemic effects. Using standards produced enzymatically by purified
      CYP11A1 and characterized by NMR, many of these new metabolites have been
      detected in human serum, with semi-quantitative measurement of 20S(OH)D3
      indicating it is present at comparable concentrations to 24R,25(OH)2D3 and 3-epi
      25(OH)D3. Recently, vitamin D-related hydroxylumisterols derived from
      lumisterol3, a previtamin D3 photoproduct, have also been measured in human serum
      and displayed biological activity in initial in vitro studies. With the current
      extensive knowledge on the reactions and pathways of metabolism of vitamin D,
      especially those catalyzed by CYP24A1, CYP27A1, CYP27B1, CYP3A4 and CYP11A1, it
      is likely that many other of the resulting hydroxyvitamin D metabolites will be
      measured in human serum in the future, some contributing to a more detailed
      understanding of vitamin D status in health and disease.

PMID- 30205157
TI  - Differential regulation of cytokine and chemokine expression by MK2 and MK3 in
      airway smooth muscle cells.
AB  - BACKGROUND: Airway smooth muscle (ASM) contributes to local inflammation and
      plays an immunomodulatory role in airway diseases. This is partially regulated by
      p38 mitogen-activated protein kinase (MAPK), which further activates two closely
      related isoforms of the MAPK-activated protein kinases (MKs), MK2 and MK3. The
      MKs have similar substrate specificities but less is known about differences in
      their functional responses. This study was undertaken to identify differential
      downstream inflammatory targets of MK2 and MK3 signaling and assess cross-talk
      between the MAPK pathway and NF-kappaB signaling relevant to ASM function.
      METHODS: Wild-type and kinase-deficient MK2 (MK2WT, MK2KR) and MK3 (MK3WT, MK33A)
      were expressed in human ASM cells stimulated for 20 h with 10 ng/ml each
      interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha and interferon (IFN)
      gamma. Inflammatory mediator secretion was assessed by Luminex assays and ELISA.
      Signaling pathway activation was monitored by Western blotting. RESULTS:
      Expression of these MKs and stimulation with 10 ng/ml IL-1beta, TNFalpha and
      IFNgamma for 20 h did not affect secretion of multiple cytokines including IL-4,
      IL-5, IL-13 and monocyte chemotactic protein (MCP)-1/CCL2 but did differentially
      affect the secretion of regulated upon activation, normal T cell expressed and
      secreted (RANTES)/CCL5, IL-6 and granulocyte macrophage-colony stimulating factor
      (GM-CSF). RANTES/CCL5 secretion was decreased by MK2WT or MK3WT and stimulated by
      inhibition of MK2 or MK3 activity with expression of the kinase-deficient enzymes
      MK2KR or MK33A. IL-6 and GM-CSF secretion was decreased by inhibition of MK2
      activity with MK2KR and while MK3WT had no effect, the kinase-deficient MK33A
      further decreased secretion of these mediators. Cross-talk of the MKs with other
      signaling pathways was investigated by examining NF-kappaB activation, which was
      inhibited by expression of MK3 but not affected by MK2. CONCLUSIONS: These
      results suggest an inhibitory role for MK2 and MK3 activity in RANTES/CCL5
      secretion and cross-talk of MK3 with NF-kappaB to regulate IL-6 and GM-CSF. These
      findings differentiate MK2 and MK3 function in ASM cells and provide insight that
      may enable selective targeting of MKs in ASM to modulate local inflammation in
      airway disease.

PMID- 30205158
TI  - Histopathological and microbiological findings and diagnostic performance of
      GeneXpert in clinically suspected tuberculous lymphadenitis.
AB  - OBJECTIVES: The primary objective was to determine the association between
      histopathological and microbiological findings in patients clinically suspected
      to have tuberculous lymphadenitis. A secondary objective was to assess the
      diagnostic utility of GeneXpert in lymph node specimens. METHOD: This was a
      single-centre prospective cohort study, performed in the Infectious Disease
      Clinic at The Indus Hospital. Three hundred and forty-one adult patients with
      chronically enlarged, accessible lymph nodes were enrolled after obtaining verbal
      consent, between February 2013 and April 2016. Tissue specimens were processed
      for histopathology, acid-fast bacillus (AFB) microscopy, AFB culture, and
      GeneXpert. Based on these results, anti-tuberculosis therapy (ATT) was
      prescribed. Clinical characteristics and treatment outcomes were recorded.
      RESULTS: There were 297 evaluable patients; 74.4% were diagnosed with tuberculous
      lymphadenitis (TBLA), 6.7% with a malignancy, and 12.8% with reactive nodes. TBLA
      was diagnosed on suggestive histopathology in 89.6% of cases, followed by
      GeneXpert (32.6%), mycobacterial culture (26.6%), and AFB smear positivity
      (12.5%). The sensitivity of GeneXpert was 65.7% when assessed against AFB
      culture. Drug resistance was displayed by 8.2% of GeneXpert-positive cases and
      11.7% of culture-positive cases. The majority of TBLA patients (88.7%) responded
      favorably to ATT. CONCLUSIONS: In light of laboratory evidence, a quarter of
      patients suspected of TBLA had an alternative diagnosis, highlighting its
      importance in avoiding over-treatment and diagnostic delays in malignancy.
      Although sensitivity is poor, the demonstration of drug resistance by both
      GeneXpert and AFB culture represents a useful tool to guide treatment.

PMID- 30205160
TI  - The Dilemma of Sex of Rearing: A Case of a 45,X/46,XY Neonate with Hydrocolpos.
AB  - BACKGROUND: A rare disorder of sex development is 45,X/46,XY mosaicism, which is
      phenotypically very heterogenous, ranging from normal male (or female) to that of
      genital ambiguity of varying degrees. CASE: We report a case of a neonate with
      45,X/46,XY mosaicism and hydrocolpos, and we point out the dilemma and the
      difficulty in gender assignment. SUMMARY AND CONCLUSION: Gender assignment of
      cases with frank genital ambiguity is often difficult to be determined, because
      several factors have to be taken into consideration, such as genital appearance,
      anticipated urological and sexual function, capacity for future fertility,
      gonadal malignancy risk, and psychosocial factors. A multidisciplinary approach
      is definitely needed in the management of such cases.

PMID- 30205159
TI  - A Preoperative Scoring System for Adnexal Mass in Children and Adolescents to
      Preserve Their Future Fertility.
AB  - STUDY OBJECTIVE: To develop a predictive score for ovarian malignancy to avoid
      unnecessary adnexectomy in cases of adnexal mass in pediatric and adolescent
      girls. DESIGN: A population-based retrospective study on girls who underwent
      surgery for an ovarian mass with normal levels of human chorionic gonadotrophin
      and alpha fetoprotein between 1996 and 2016. SETTING: Rennes University Hospital,
      Rennes, France. PARTICIPANTS: Eighty-one patients who received surgery for
      ovarian tumor. MAIN OUTCOME MEASURES: The main outcome measure was the rate of
      malignant and borderline tumor. A preoperative scoring system was constructed
      after multivariate analysis. RESULTS: The rate of malignant ovarian tumor was
      6/81 (7%), borderline tumor was 7/81 (9%) (ie, outcome measure: 16%), and benign
      tumor was 84%. In a univariate analysis, the characteristics significantly
      associated with malignancy were early puberty, palpable mass, size and content of
      the tumor, and positive epithelial tumor markers (carcinoma antigen 125,
      carcinoembryonic antigen, and carcinoma antigen 19-9). The predictive malignancy
      score was on the basis of 2 variables obtained after multivariate analysis: tumor
      size and cystic content. The score defined 3 groups at risk for malignancy: low
      risk, middle-risk, and high-risk. The sensitivity for detecting malignancy was
      1.3% (95% confidence interval [CI], 0.1-18.4), 26.2% (95% CI, 11.6-49.0), and
      53.1% (95% CI, 29.1-75.8), respectively. CONCLUSION: We set up a simple
      predictive score of malignancy on the basis of objective criteria to help
      decision-making on whether or not ovarian-sparing surgery is feasible in case of
      children and adolescents with ovarian tumors and normal human chorionic
      gonadotrophin and alpha fetoprotein levels while ensuring oncologic safety.

PMID- 30205162
TI  - Multiple calcifying hyperplastic dental follicles.

PMID- 30205161
TI  - CaMKII inhibition in human primary and pluripotent stem cell-derived chondrocytes
      modulates effects of TGFbeta and BMP through SMAD signaling.
AB  - OBJECTIVE: Upregulation of calcium/calmodulin-dependent kinase II (CaMKII) is
      implicated in the pathogenesis of osteoarthritis (OA) and reactivation of
      articular cartilage hypertrophy. However, direct inhibition of CaMKII
      unexpectedly augmented symptoms of OA in animal models. The role of CaMKII in OA
      remains unclear and requires further investigation. METHODS: Analysis of CaMKII
      expression was performed in normal human and OA articular chondrocytes, and
      signaling mechanisms were assessed in articular, fetal and Pluripotent Stem Cell
      (PSC)-derived human chondrocytes using pharmacological (KN93), peptide (AC3-I)
      and small interfering RNA (siRNA) inhibitors of CaMKII. RESULTS: Expression
      levels of phospho-CaMKII (pCaMKII) were significantly and consistently increased
      in human OA specimens. BMP2/4 activated expression of pCaMKII as well as COLII
      and COLX in human adult articular chondrocytes, and also increased the levels and
      nuclear localization of SMADs1/5/8, while TGFbeta1 showed minimal or no
      activation of the chondrogenic program in adult chondrocytes. Targeted blockade
      of CaMKII with specific siRNAs decreased levels of pSMADs, COLII, COLX and
      proteoglycans in normal and OA adult articular chondrocytes in the presence of
      both BMP4 and TGFbeta1. Both human fetal and PSC-derived chondrocytes also
      demonstrated a decrease of chondrogenic differentiation in the presence of small
      molecule and peptide inhibitors of CaMKII. Furthermore, immunoprecipitation for
      SMADs1/5/8 or 2/3 followed by western blotting for pCaMKII showed direct
      interaction between SMADs and pCaMKII in primary chondrocytes. CONCLUSION:
      Current study demonstrates a direct role for CaMKII in TGF-beta and BMP-mediated
      responses in primary and PSC-derived chondrocytes. These findings have direct
      implications for tissue engineering of cartilage tissue from stem cells and
      therapeutic management of OA.

PMID- 30205163
TI  - Analysis of the Reproductive Outcome of Patients with Cesarean Scar Pregnancy
      Treated by High-Intensity Focused Ultrasound and Uterine Artery Embolization: A
      Retrospective Cohort Study.
AB  - STUDY OBJECTIVE: To investigate risk factors for infertility and recurrent
      cesarean scar pregnancy (CSP) after previous CSP. DESIGN: A retrospective cohort
      study (Canadian Task Force classification II-1). SETTING: University hospital.
      PATIENTS: Between January 2007 and April 2016, a total of 650 patients were
      included, all diagnosed with CSP and treated by high-intensity focused ultrasound
      (HIFU) and uterine artery embolization (UAE), followed by suction curettage under
      hysteroscopic guidance. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Follow
      up of the reproductive outcomes ended in June 2017. A total of 135 of the 650
      patients with CSP were involved in the study, among whom 32 became infertile, 78
      had an intrauterine pregnancy, and 25 had recurrent CSP after previous CSP. Age
      (>=35 years; odds ratio [OR], 4.252; p = .002), beta-human chorionic gonadotropin
      (<=5000 mIU/mL; OR, 3.778; p = .011), and longer duration of amenorrhea (>56
      days; OR, 2.507; p = .05) were risk factors for infertility. Treatment with UAE
      (OR, 5.796; p = .003), more abortions (>=4; OR, 2.851; p = .022), and being
      asymptomatic (OR, 4.175; p = .039) were risk factors for recurrent CSP. There was
      no statistically significant difference in the subsequent outcomes of pregnant
      women in the HIFU and UAE groups (p >.05). CONCLUSION: More attention should be
      given to subsequent reproductive outcomes after CSP, not only for intrauterine
      pregnancy, but also for infertility and recurrent CSP. Early diagnosis and
      treatment of CSP could reduce the risk of infertility and recurrent CSP. HIFU
      seemed to be superior to UAE in reducing the risk of recurrent CSP. Patients with
      CSP should adhere to strict contraception if they do not desire more children.

PMID- 30205164
TI  - Persistence of Symptoms After Total vs Supracervical Hysterectomy in Women with
      Histopathological Diagnosis of Adenomyosis.
AB  - STUDY OBJECTIVE: To compare symptom persistence in women with adenomyosis based
      on retention or removal of the cervix at the time of hysterectomy. DESIGN:
      Retrospective cohort study and follow-up survey (Canadian Task Force
      classification xx). SETTING: Tertiary care academic hospital in Boston,
      Massachusetts. PATIENTS: Women (n = 1580) who underwent laparoscopic hysterectomy
      for benign indications between 2008 and 2012 at Brigham and Women's Faulkner
      Hospital and Brigham and Women's Hospital. INTERVENTION: Retrospective chart
      review and follow-up survey. MEASUREMENTS AND MAIN RESULTS: Among the 1580 women
      contacted, 762 (48%) responded to the postoperative symptom resolution survey. Of
      these 762 women, 623 agreed to participate in the study. Menopausal women or
      those who had undergone bilateral salpingo-oophorectomy were excluded.
      Adenomyosis was identified on histopathologic evaluation of the uterus in 171 of
      the remaining 443 women (39%). Compared with women without adenomyosis, those
      with adenomyosis were older on average (mean age, 46.6 +/- 6.8years vs 45.0 +/-
      5.5 years; p = .009) and more likely to report that abnormal bleeding and pain
      led to their hysterectomy (87.7% vs 79.8%; p = .03 and 64.9% vs 51.4%; p = .009,
      respectively). The rates of total and supracervical hysterectomies were similar
      in the 2 groups. Following surgery, women with adenomyosis were less likely than
      those without adenomyosis to report persistent pain (adjusted odds ratio [aOR],
      0.43; 95% confidence interval [CI], 0.20-0.93; p = .03). Persistent bleeding was
      similar in the 2 groups (aOR, 0.97; 95% CI, 0.49-1.93; p = .94). Among women with
      adenomyosis, multivariable logistic regression showed no difference in
      persistence of symptoms with cervical removal or retention at the time of
      hysterectomy. CONCLUSION: Compared with women without adenomyosis, those with
      histopathologically proven adenomyosis were less likely to report persistent pain
      following hysterectomy. Retention of the cervix does not appear to increase the
      risk of symptom persistence or postprocedure patient satisfaction.

PMID- 30205165
TI  - Identification of a High-Level MET Amplification in CTCs and cfTNA of an ALK
      Positive NSCLC Patient Developing Evasive Resistance to Crizotinib.

PMID- 30205167
TI  - Targeting SLC25A10 alleviates improved antioxidant capacity and associated
      radioresistance of cancer cells induced by chronic-cycling hypoxia.
AB  - High tumor heterogeneity and increased therapy resistance acquired in a hypoxic
      tumor microenvironment remain major obstacles to successful radiotherapy. Others
      and we have shown that adaptation of cancer cells to cycling severe hypoxia and
      intermittent reoxygenation stress (chronic-cycling hypoxia) increases cellular
      antioxidant capacity thereby supporting resistance to chemotherapy and
      radiotherapy. Here we explored the involvement of antioxidant-associated
      mitochondrial transport-systems for maintenance of redox-homeostasis in
      adaptation to chronic-cycling hypoxia and associated radioresistance. Genetic or
      pharmacological inhibition of the mitochondrial dicarboxylate carrier (SLC25A10)
      or the oxoglutarate-carrier (SLC25A11) increased the cytotoxic effects of
      ionizing radiation (IR). But only targeting of SLC25A10 was effective in
      overcoming chronic-cycling hypoxia-induced enhanced death resistance in vitro and
      in vivo by disturbing increased antioxidant capacity. Furthermore, in silico
      analysis revealed that overexpression of SLC25A10 but not SLC25A11 is associated
      with reduced overall survival in lung- and breast-cancer patients. Our study
      reveals a role of SLC25A10 in supporting both, redox- and energy-homeostasis,
      ensuring radioresistance of cancer cells with tolerance to chronic-cycling
      hypoxia thereby proposing a novel strategy to overcome a mechanism of hypoxia
      induced therapy resistance with potential clinical relevance regarding decreased
      patient survival.

PMID- 30205166
TI  - Increased Hepatotoxicity Associated with Sequential Immune Checkpoint Inhibitor
      and Crizotinib Therapy in Patients with Non-Small Cell Lung Cancer.
AB  - INTRODUCTION: Immune checkpoint inhibitors (ICIs) are standard therapies in
      advanced NSCLC. Although genotype-directed tyrosine kinase inhibitors represent
      the standard of care for subsets of oncogene-driven NSCLC, patients may receive
      ICIs during their disease course. The impact of sequential ICI and tyrosine
      kinase inhibitor therapy on the risk of hepatotoxicity has not been described.
      METHODS: Patients with advanced ALK receptor tyrosine kinase (ALK)-driven, ROS1
      driven, or MET proto-oncogene, receptor tyrosine kinase (MET)-driven NSCLC
      treated with crizotinib, with or without preceding ICI therapy, were identified.
      The cumulative incidences of crizotinib-associated grade 3 or higher increases in
      transaminase level (per the Common Terminology Criteria for Adverse Events,
      version 4.0) were compared. RESULTS: We identified 453 patients with NSCLC who
      harbored an oncogenic alteration in ALK receptor tyrosine kinase gene (ALK),
      ROS1, or MET proto-oncogene, receptor tyrosine kinase gene (MET) who were treated
      with crizotinib (11 with and 442 without prior ICI therapy). Among the 11
      patients treated with an ICI followed by crizotinib, five (cumulative incidence
      45.5% [95% confidence interval (CI): 14.9-72.2]) experienced development of a
      grade 3 or 4 increase in alanine transaminase level and four (cumulative
      incidence 36.4% [95% CI: 10.0-64.2]) experienced development of a grade 3 or 4
      increase in aspartate transaminase level. In comparison, among the 442 patients
      who received crizotinib only, a grade 3 or 4 increase in alanine transaminase
      level occurred in 34 patients (cumulative incidence 8.1% [95% CI: 5.7-11.0, p <
      0.0001]) and a grade 3 or 4 increase in aspartate transaminase level occurred in
      14 (cumulative incidence 3.4% [95% CI: 1.9-5.5, p < 0.0001]). There were no grade
      5 transaminitis events. All cases of hepatotoxicity after sequential ICI and
      crizotinib use were reversible and nonfatal, and no case met the Hy's law
      criteria. CONCLUSIONS: Sequential ICI and crizotinib treatment is associated with
      a significantly increased risk of hepatotoxicity. Careful consideration and
      monitoring for hepatotoxicity may be warranted in patients treated with
      crizotinib after ICI therapy.

PMID- 30205168
TI  - Hydroxycoumarin OT-55 kills CML cells alone or in synergy with imatinib or
      Synribo: Involvement of ER stress and DAMP release.
AB  - We synthetized and investigated the anti-leukemic potential of the novel
      cytostatic bis(4-hydroxycoumarin) derivative OT-55 which complied with the
      Lipinski's rule of 5 and induced differential toxicity in various chronic myeloid
      leukemia (CML) cell models. OT-55 triggered ER stress leading to canonical,
      caspase-dependent apoptosis and release of danger associated molecular patterns.
      Consequently, OT-55 promoted phagocytosis of OT-55-treated CML cells by both
      murine and human monocyte-derived macrophages. Moreover, OT-55 inhibited tumor
      necrosis factor alpha-induced activation of nuclear factor-kB and produced
      synergistic effects when used in combination with imatinib to inhibit colony
      formation in vitro and Bcr-Abl+ patient blast xenograft growth in zebrafish.
      Furthermore, OT-55 synergized with omacetaxine in imatinib-resistant KBM-5 R
      cells to inhibit the expression of Mcl-1, triggering apoptosis. In imatinib
      resistant K562 R cells, OT-55 triggered necrosis and blocked tumor formation in
      zebrafish in combination with omacetaxine.

PMID- 30205169
TI  - IFN-gamma synergism with poly I:C reduces growth of murine and human cancer cells
      with simultaneous changes in cell cycle and immune checkpoint proteins.
AB  - Previously, we reported that IFN-gamma and poly I:C, a TLR3 Pattern Recognition
      Receptor (PRR) agonist, reduces growth of and induces Cleaved-Caspase-3, ISG54
      and p27Kip in B16 melanoma cells. Here, analysis of IFN-gamma/PRR synergism was
      expanded with UM-SCC1 and UM-SCC38 human squamous carcinoma cells and other PRR
      agonists. As in B16 cells, poly I:C plus IFN-gamma synergism reduced UM-SCC1 and
      UM-SCC38 growth, and no more than 24 h was needed for significant growth
      reduction. IFN-gamma synergism to stem B16 growth also occurred with TLR7, TLR9,
      TLR4, and STING agonists, but not TLR2 agonist. IFN-gamma synergized with TLR3
      and TLR4 agonists reducing UM-SCC1 growth, and with TLR7 and TLR3 agonists
      reducing UM-SCC38 growth. IFN-gamma plus poly I:C, which had the most pronounced
      effect, decreased cyclin-D1, increased G1 cell cycle arrest, and increased
      Cleaved caspase-3 in B16 cells, as well as RAW264.7, a virus-transformed murine
      macrophage cell line. Finally, IFN-gamma plus poly I:C modulated total but not
      cell surface expression of immune checkpoint protein PD-L1, as well as cell cycle
      checkpoint proteins in B16 cells. Thus IFN-gamma plus poly I:C, and other PRR
      agonists, may well be effective adjuvants to cancer immunotherapy against several
      tumor cell types.

PMID- 30205170
TI  - 3D in vitro models of tumors expressing EGFR family receptors: a potent tool for
      studying receptor biology and targeted drug development.
AB  - Carcinomas overexpressing EGFR family receptors are of high clinical importance,
      because the receptors have prognostic value and are used as molecular targets for
      anticancer therapy. Insufficient drug efficacy necessitates further in-depth
      research of the receptor biology and improvement in preclinical stages of drug
      evaluation. Here, we review the currently used advanced 3D in vitro models of
      tumors, including tumor spheroids, models in natural and synthetic matrices,
      tumor organoids and microfluidic-based models, as a potent tool for studying EGFR
      biology and targeted drug development. We are especially focused on factors that
      affect the biology of tumor cells, causing modification in the expression and
      basic phosphorylation of the receptors, crosstalk with other signaling pathways
      and switch between downstream cascades, resulting ultimately in the resistance to
      antitumor agents.

PMID- 30205171
TI  - Quality assurance of biomedical terminologies and ontologies.

PMID- 30205172
TI  - Supporting biomedical ontology evolution by identifying outdated concepts and the
      required type of change.
AB  - The consistent evolution of ontologies is a major challenge for systems using
      semantically enriched data, for example, for annotating, indexing, or reasoning.
      The biomedical domain is a typical example where ontologies, expressed with
      different formalisms, have been used for a long time and whose dynamic nature
      requires the regular revision of underlying systems. However, the automatic
      identification of outdated concepts and proposition of revision actions to update
      them are still open research questions. Solutions to these problems are of great
      interest to organizations that manage huge and dynamic ontologies. In this paper,
      we present an approach for (i) identifying the concepts of an ontology that
      require revision and (ii) suggesting the type of revision. Our analysis is based
      on three aspects: structural information encoded in the ontology, relational
      information gained from external source of knowledge (i.e., PubMed and UMLS) and
      temporal information derived from the history of the ontology. Our approach aims
      to evaluate different methods and parameters used by supervised learning
      classifiers to identify both the set of concepts that need revision, and the type
      of revision. We applied our approach to four well-known biomedical
      ontologies/terminologies (ICD-9-CM, MeSH, NCIt and SNOMED CT) and compared our
      results to similar approaches. Our model shows accuracy ranging from 68% (for
      SNOMED CT) to 91% (for MeSH), and an average of 71% when considering all datasets
      together.

PMID- 30205173
TI  - Identification and characterization of microRNAs in the liver of rainbow trout in
      response to heat stress by high-throughput sequencing.
AB  - MicroRNAs (miRNAs) play key roles in the stress response in animals. The rainbow
      trout is a widely cultivated cold-water fish species that usually encounters heat
      stress, which affects its growth and may cause diseases. However, there is
      limited information on the miRNAs involved in heat stress in this species. To
      identify the heat-responsive miRNAs at the genome level in rainbow trout, we
      conducted high-throughput sequencing of 6 small RNA libraries from the liver
      tissues of rainbow trout specimens under control and heat-treated conditions. A
      total of 363 conserved miRNAs and 638 novel miRNAs were identified, among which
      39 (21 conserved and 18 novel) miRNAs were differentially expressed in response
      to heat stress. Eight important miRNAs were further validated using quantitative
      real-time PCR. GO enrichment and KEGG pathway analyses of the potential target
      genes of the DE miRNAs, revealed DNA replication and protein folding and
      unfolding were affected by heat stress. Several key pathways involved in the heat
      stress response were characterized, such as protein processing in the endoplasmic
      reticulum, NOD-like receptor signaling pathway, and progesterone-mediated oocyte
      maturation. In addition, 20 important functional interaction pairs among the 65
      negatively correlated miRNA-mRNA pairs were identified using integrated miRNA
      mRNA analysis and miRNA prediction algorithms, which including potential
      important miRNAs and target genes such as miR-301a, miR-301d, let-7c, novel_1181
      and HSP90BA, HSP90BB, HSP40, PDIA3. This study showed that the identified miRNAs
      probably play important roles in the heat stress response and lay a foundation
      for further studies on the thermal adaptation mechanisms in rainbow trout.

PMID- 30205174
TI  - Can the choice of diet undermine the potential genetic risk of AT1R 1166A>C gene
      polymorphism?
AB  - BACKGROUND: Angiotensin II type 1 receptor (AT1R) gene 1166A>C polymorphism is
      strongly associated with the incidence of cardiovascular diseases and predicts
      the development of metabolic syndrome (MetS). There is little information about
      the gene-diet interactions associated with MetS. This investigation examined the
      interaction between dietary patterns and AT1R polymorphism in relation to
      development risk of MetS. METHODS: A prospective, non-interventional, case
      control study included 265 MetS patients and 262 healthy controls in an adult
      population from Croatia. Collected data included clinical variables, type of diet
      (Mediterranean, continental and mixed), biochemical tests and AT1R genotyping.
      AT1R 1166A>C genotyping was performed by PCR restriction fragment length
      polymorphism methods. To examine gene-diet interactions, a total predictive model
      was built using a hierarchical backward elimination approach. RESULTS:
      Participants on Continental-diet were nearly 20 times more likely to have MetS
      than those on Mediterranean or mixed diet (OR = 19.96; 95% CI 10.44-38.18). In
      multivariate prediction, control subjects with AT1R 1166AC or CC genotype had a
      higher risk for high triglycerides compared to the AA genotype carriers. 1166AC
      or CC genotype carriers more often chose Mediterranean or mixed-diet versus
      1166AA genotype carriers whose choice often was continental diet. CONCLUSIONS:
      Our results are the first to suggest the possibility that the choice of diet can
      undermine the potential genetic risk of the AT1R polymorphism as polymorphism
      carriers may spontaneously choose the Mediterranean-diet.

PMID- 30205175
TI  - Lentiviral vector expression of Klf4 enhances chondrogenesis and reduces
      hypertrophy in equine chondrocytes.
AB  - Monolayer expansion of chondrocytes in culture results in the dedifferentiation
      of chondrocytes with inferior cartilage specific extracellular matrix synthesis
      and proliferation when compared with its native counterpart. We aimed to enhance
      chondrocyte proliferation and articular cartilage specific gene expression
      through ectopic expression of the major pluripotency transcription factors (Oct4,
      Sox2, Klf4 and c-Myc). We also aimed to provide insights to the modulation of
      TGFbeta receptor mRNA with Klf4 overexpression. Equine chondrocytes pooled from
      three donors were transduced with lentiviral vectors expressing the induced
      pluripotency factors, Oct4, Sox2. Klf4 and c-Myc (OSKM), singly, or in
      combination or together with green fluorescent protein (GFP) as a control. Klf4
      and c-Myc overexpressing chondrocytes showed a significant increase in mitosis
      when compared to the control (P < 0.01 and P < 0.0001 respectively). Furthermore,
      overexpression of Klf4 or OSKM in three dimensional (3D) culture of equine
      chondrocytes resulted in a significant increase in Col2a1 mRNA levels relative to
      the controls (P < 0.05 and P < 0.01 respectively) while all transcription factors
      significantly lowered the mRNA of the fibrocartilage marker Col1a1. We also
      employed a Col2a1 promoter driven GFP reporter for real time monitoring of Col2a1
      gene activation in 3D micromass culture, which showed significantly higher
      promoter activity when cultures were treated with the growth factor TGFbeta3 (P <
      0.05). The chondrogenic properties of Klf4 transduced chondrocytes at a lower
      passage (P4) showed significant increases in Sox9 (P < 0.001), Col2a1 (P < 0.05)
      and TGFbeta receptor I (P < 0.05) and II (P < 0.001) expression relative to the
      DS-Red expressing control. The chondrocyte dedifferentiation marker Col1a1 and
      hypertrophic marker Col10a1 were significantly downregulated with the inclusion
      of Klf4 (P < 0.01 and P < 0.05 respectively). In Conclusion, chondrogenic re
      differentiation and proliferation of equine chondrocytes is promoted through
      ectopic expression of Klf4 while suppressing chondrocyte dedifferentiation.

PMID- 30205178
TI  - Whole exome sequencing identifies both nuclear and mitochondrial variations in an
      Iranian family with non-syndromic hearing loss.
AB  - Genetic contributing factors to non-syndromic hearing loss (NSHL) are remarkably
      diverse spanning over autosomal to X-linked to mitochondrial inheritance
      patterns. Facing a quite unconventional pedigree, here we report implementation
      of whole exome sequencing (WES) to uncover mitochondrial pathogenic variant in a
      six-generation Iranian family with four cases affected with hereditary NSHL of
      variable severity. As a result, heteroplasmic transition of A to G at position
      1555 of MT-RNR1 gene was identified in all affected individuals co-existing with
      nuclear c.28G > T (p.A10S) variant in the TRMU gene, only in some patients. The
      reliability of WES to infer nuclear as well as mitochondrial variants in hearing
      loss were discussed.

PMID- 30205177
TI  - Immunogenicity to cerliponase alfa intracerebroventricular enzyme replacement
      therapy for CLN2 disease: Results from a Phase 1/2 study.
AB  - Treatment with intracerebroventricular (ICV)-delivered cerliponase alfa enzyme
      replacement therapy (ERT) in a Phase 1/2 study of 24 subjects with CLN2 disease
      resulted in a meaningful preservation of motor and language (ML) function and was
      well tolerated. Treatment was associated with anti-drug antibody (ADA) production
      in the cerebrospinal fluid (CSF) of 6/24 (25%) and in the serum of 19/24 (79%) of
      clinical trial subjects, respectively, over a mean exposure of 96.4 weeks (range
      0.1-129 weeks). Neutralizing antibodies (NAb) were not detected in the CSF of any
      of the subjects. No events of anaphylaxis were reported. Neither the presence of
      serum ADA nor drug-specific immunoglobulin E was associated with the incidence or
      severity of hypersensitivity adverse events. Serum and CSF ADA titers did not
      correlate with change in ML score. Therefore, the development of an ADA response
      to cerliponase alfa is not predictive of an adverse safety profile or poor
      treatment outcome.

PMID- 30205176
TI  - MiR-875 and miR-3144 switch the human papillomavirus 16 E6/E6* mRNA ratio through
      the EGFR pathway and a direct targeting effect.
AB  - : By employing bioinformatics scanning approaches and luciferase reporter, our
      previous study showed that two less common human miRNAs, miR-875 and miR-3144,
      target a conserved site in the genomes of most high-risk human papillomaviruses
      (HR-HPVs). In this study, we found that the site targeted by miR-875 and miR-3144
      overlapped with the 5' alternative splice site of E6E7 transcripts in HPV16.
      Using HPV16+ SiHa cells, we showed that high levels of miR-875 and miR-3144
      reduced the abundance of unspliced E6, while they promoted three E6* spliced
      transcripts and decreased the expression levels of E6/E7 oncoproteins and
      epidermal growth factor receptor (EGFR). A potential miR-875 target site was
      predicted in EGFR. Meanwhile, depletion of EGFR resulted in a failure to promote
      E6* but maintained the suppression of unspliced E6 driven by miR-875 and miR
      3144. The data suggest that these two miRNAs switch the E6/E6* ratio through both
      the EGFR pathway and direct targeting. Here, we demonstrate for the first time
      that human miRNAs regulate the HPV splice isoforms. Furthermore, miRNA-875 and
      miRNA-3144 are only found in vertebrates and Homo sapiens, and the binding site
      in EGFR is highly conserved in Boreoeutheria. Our findings highlight the tumour
      suppressing effect of miRNAs that possibly appeared in the late stage of
      biological evolution. ABBREVIATIONS: 

PMID- 30205179
TI  - Fractional-order Darwinian PSO-based feature selection for media-adventitia
      border detection in intravascular ultrasound images.
AB  - Media-adventitia (MA) border delineates the outer appearance of arterial wall in
      intravascular ultrasound (IVUS) image. The detection of MA border is a
      challenging topic due to many difficulties such as complicated intravascular
      structures, intrinsic artifacts and image noises. We propose a classification
      based MA border detection method with an embedded feature selection technique.
      The feature selection technique is based on Fractional-order Darwinian particle
      swarm optimization (FODPSO) algorithm. By employing feature selection, 293
      dimension features including multi-scale features, gray-scale features and
      morphological feature are reducing to 37-dimension. The border detection method
      with feature selection is tested on a public dataset extracted from in-vivo
      pullbacks of human coronary arteries, which contains 77 IVUS images. Three
      indicators, Jaccard (JACC), Hausdorff Distance (HD) and Percentage of Area
      Difference (PAD), are measured for quantitative evaluation. Detection with 293
      dimension features obtains JACC 0.79, HD 1.41 and PAD 0.16, while detection with
      37-dimension features obtains JACC 0.83, HD 1.27 and PAD 0.12, indicating that
      the FODPSO-based feature selection method improves MA border detection by JACC
      0.04, HD 0.14 and PAD 0.04. Furthermore, the proposed border detection method
      acquires better performances compared with two other automatic methods conducted
      on the same dataset available in literature.

PMID- 30205180
TI  - Myorelaxant Activity of essential oil from Origanum majorana L. on rat and
      rabbit.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Origanum majorana L. (Lamiaceae) was usually used
      in Moroccan folk medicine to treat infantile colic and abdominal discomfort.
      MATERIALS AND METHODS: The essential oil from the aerial part of the dry Origanum
      majorana L. (EOOM) was obtained through hydro distillation and analyzed by gas
      chromatography/mass spectrometry (GC/MS). The effect of EOOM on muscle relaxation
      was measured on rabbit and rat intestinal smooth muscle mounted in an isotonic
      transducer. RESULTS: 1) The main compounds obtained from the aqueous extract of
      this plant were alpha Terpineol, L-terpinen-4-ol and Beta.-Linalool. 2) EOOM
      inhibited in a concentration-dependent manner spontaneous contraction of rabbit
      jejunum, with an IC50 = 64.08 +/- 2.42 MUg/mL. 3) In rat intestine, EOOM induced
      the relaxation of the tissue in concentration-dependent manner with an IC50 =
      39.70 +/- 2.29 MUg/mL when the tissue was pre-contracted with CCh 10-6 M, and
      48.70 +/- 2.26 MUg/mL when the tissue was pre-contracted with 25 mM KCl. 4) The
      relaxation effect induced by EOOM was more important than that obtained in the
      presence of atropine, hexamethonium, Nifedipine, L-NAME and Blue of methylene.
      CONCLUSION: the present result indicates that essential oil of Origanum majorana
      L. exhibit an effect on intestinal relaxation in vitro. This effect further
      validates the traditional use of Origanum majorana L. to treat infantile colic
      and abdominal discomfort.

PMID- 30205181
TI  - Cannabis sativa: A comprehensive ethnopharmacological review of a medicinal plant
      with a long history.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Cannabis sativa L. (C. sativa) is an annual
      dioecious plant, which shares its origins with the inception of the first
      agricultural human societies in Asia. Over the course of time different parts of
      the plant have been utilized for therapeutic and recreational purposes, for
      instance, extraction of healing oils from seed, or the use of inflorescences for
      their psychoactive effects. The key psychoactive constituent in C. sativa is
      called Delta-9-tetrahydrocannabinol (D9-THC). The endocannabinoid system seems to
      be phylogenetically ancient, as it was present in the most primitive vertebrates
      with a neuronal network. N-arachidonoylethanolamine (AEA) and 2-arachidonoyl
      glycerol (2-AG) are the main endocannabinoids ligands present in the animal
      kingdom, and the main endocannabinoid receptors are cannabinoid type-1 (CB1)
      receptor and cannabinoid type-2 (CB2) receptor. AIM OF THE STUDY: The review aims
      to provide a critical and comprehensive evaluation, from the ancient times to our
      days, of the ethnological, botanical, chemical and pharmacological aspects of C.
      sativa, with a vision for promoting further pharmaceutical research to explore
      its complete potential as a therapeutic agent. MATERIALS AND METHODS: This study
      was performed by reviewing in extensive details the studies on historical
      significance and ethnopharmacological applications of C. sativa by using
      international scientific databases, books, Master's and Ph.D. dissertations and
      government reports. In addition, we also try to gather relevant information from
      large regional as well as global unpublished resources. In addition, the plant
      taxonomy was validated using certified databases such as Medicinal Plant Names
      Services (MPNS) and The Plant List. RESULTS AND CONCLUSIONS: A detailed
      comparative analysis of the available resources for C. sativa confirmed its
      origin and traditional spiritual, household and therapeutic uses and most
      importantly its popularity as a recreational drug. The result of several studies
      suggested a deeper involvement of phytocannabinoids (the key compounds in C.
      sativa) in several others central and peripheral pathophysiological mechanisms
      such as food intake, inflammation, pain, colitis, sleep disorders, neurological
      and psychiatric illness. However, despite their numerous medicinal benefits, they
      are still considered as a menace to the society and banned throughout the world,
      except for few countries. We believe that this review will help lay the
      foundation for promoting exhaustive pharmacological and pharmaceutical studies in
      order to better understand the clinical relevance and applications of non
      psychoactive cannabinoids in the prevention and treatment of life-threatening
      diseases and help to improve the legal status of C. sativa.

PMID- 30205182
TI  - Evaluating the clinical implementation of structured exercise: A randomized
      controlled trial among non-insulin dependent type II diabetics.
AB  - BACKGROUND: The American Diabetes Association (ADA) currently recommends 150 min
      of moderate-intensity aerobic exercise per week and resistance exercise at least
      twice per week in individuals with type 2 diabetes (T2DM) to improve overall
      health [1]. However, approximately 38% of patients with T2DM do not exercise at
      recommended levels and 31% do not exercise at all [2]. The efficacy of structured
      exercise interventions has been proven effective in reducing glycosylated
      hemoglobin A1c (HbA1c) levels in patients, but practical approaches are needed to
      translate these findings into the clinical setting [3-7]. OBJECTIVE: The Initiate
      and Maintain Physical Activity in Clinics (IMPACT) Study aims to compare
      structured group exercise within the clinic to usual care in T2DM patients. The
      main purpose of the study is to determine the optimal and feasible level and
      weekly frequency of structured contact in a clinical setting needed to initiate
      and maintain physical activity recommendations long-term. STUDY DESIGN: IMPACT is
      a longitudinal, randomized-controlled study designed to track study participants
      over 30 months. Once study participants have met eligibility and enrollment
      criteria, they are randomized and enrolled into one of three arms: 1* per week
      exercise, 3* per week exercise, or the usual care control group. After
      randomization, participants begin Phase 1: Initiate lasting 6 months. Over the
      course of Phase 1, participants in the exercise groups will attend instructor led
      group training at a Stanford approved physical fitness facility. At the end of 6
      months, participants enter Phase 2: Maintain lasting 24 months. Over the course
      of Phase 2, participants in all three arms will attend periodic follow-up visits
      for clinical measurements and survey administration for their final two years of
      participation. These findings will enable the clinical implementation of a
      structured exercise regimen designed to specifically address the aerobic and
      resistance training recommendations for patients with T2DM.

PMID- 30205183
TI  - Indicators of socio-economic status and risk of gestational diabetes mellitus in
      pregnant women in urban Tianjin, China.
AB  - AIMS: To examine associations between the indicators of socio-economic status
      (SES) and gestational diabetes mellitus (GDM). METHODS: From 2010 to 2012, 17 659
      women underwent glucose challenge test (GCT) and oral glucose tolerance test if
      GCT >= 7.8 mmol/L at 24-28 gestational weeks in 6 urban districts of Tianjin,
      China. Binary logistic regression was used to obtain adjusted odds ratio (OR) of
      SES for GDM, as defined by education attainment and family monthly income.
      RESULTS: A total of 1264 women (7.2%) were found to have GDM. If the women with
      low-middle income and high school or below used as the reference group, the
      middle-high income group and the high income group were associated with decreased
      risks of GDM (OR: 0.85, 95%CI: 0.71-1.00 & 0.80, 0.65-0.98) while tertiary
      education attainment was associated with decreased risk of GDM (0.75, 0.58-0.97).
      Women with higher income and/or higher education attainment tended to have a
      decreased risk of GDM (P for trend: 0.0105). All these significant ORs were
      attenuated to be non-significant by adjustment for pre-pregnancy body mass index
      (BMI), but not by adjustment for gestational weight gain (GWG). CONCLUSIONS: In
      urban Tianjin, indicators of high SES were associated with decreased risk of GDM
      via decreased pre-pregnancy BMI.

PMID- 30205184
TI  - Integrated personalized diabetes management improves glycemic control in patients
      with insulin-treated type 2 diabetes: Results of the PDM-ProValue study program.
AB  - AIMS: Globally, many patients with insulin-treated type-2 diabetes are
      suboptimally controlled. The PDM-ProValue study program evaluated whether
      integrated personalized diabetes management (iPDM) has the potential to improve
      clinical outcomes. METHODS: 101 practices with 907 patients participated in the
      12-month, prospective, controlled, cluster-randomized study program. HbA1c
      levels, therapy changes, frequency of hypoglycemic episodes, patient reported
      outcomes, and physician satisfaction were assessed. RESULTS: iPDM led to a
      greater reduction in HbA1c after 12 months vs. usual care (-0.5%, p < 0.0001 vs. 
      0.3%, p < 0.0001), (Diff. 0.2%, p = 0.0324). Most of the HbA1c reduction occurred
      after 3 months and remained stable thereafter. The percentage of patients with
      therapy adjustments was higher in the iPDM group at all visits (p < 0.01 at week
      3, month 3, month 6). Patient adherence at month 12 was higher in the iPDM group
      compared to baseline (Odds ratio = 2.39; p = 0.0003); also, patient treatment
      satisfaction (DTSQc: 12.2 vs. 10.4, delta = 1.78, p = 0.004; DTSQs: 31.0 vs.
      30.0, delta = 0.924, p = 0.02), and physician satisfaction was higher in the
      intervention group. CONCLUSIONS: iPDM improved the use of diagnostic data leading
      to better glycemic control, more timely treatment adjustments (indicating reduced
      clinical inertia), and increased patient adherence and treatment satisfaction
      among patients and physicians.

PMID- 30205185
TI  - Differential expression of functional chemokine receptors on human blood and lung
      group 2 innate lymphoid cells.

PMID- 30205186
TI  - Signal transducer and activator of transcription 5B deficiency due to a novel
      missense mutation in the coiled-coil domain.

PMID- 30205187
TI  - Tobacco smoke as a risk factor for allergic sensitization in adults: Conclusions
      of a systematic review and meta-analysis.

PMID- 30205188
TI  - Lower perinatal exposure to Proteobacteria is an independent predictor of early
      childhood wheezing.

PMID- 30205189
TI  - Anti-IL-5 treatments in patients with severe asthma by blood eosinophil
      thresholds: Indirect treatment comparison.
AB  - BACKGROUND: Three anti-IL-5 pathway-directed therapies are approved for use in
      patients with severe eosinophilic asthma (SEA); however, no head-to-head
      comparison data are available. OBJECTIVE: We sought to compare the efficacy of
      licensed doses of mepolizumab, benralizumab, and reslizumab in patients with SEA,
      according to baseline blood eosinophil counts. METHODS: This indirect treatment
      comparison (ITC) used data from a Cochrane review and independent searches.
      Eligible studies were randomized controlled trials in patients aged 12 years or
      greater with SEA. End points included annualized rate of clinically significant
      exacerbations and change from baseline in Asthma Control Questionnaire score and
      FEV1. An ITC was performed in patients with Asthma Control Questionnaire scores
      of 1.5 or greater and stratified by baseline blood eosinophil count. RESULTS:
      Eleven studies were included. All treatments significantly reduced the rate of
      clinically significant exacerbations and improved asthma control versus placebo
      in all blood eosinophil count subgroups. Mepolizumab reduced clinically
      significant exacerbations by 34% to 45% versus benralizumab across subgroups
      (rate ratio >=400 cells/MUL: 0.55 [95% CI, 0.35-0.87]; >=300 cells/MUL: 0.61 [95%
      CI, 0.37-0.99]; and >=150 cells/MUL: 0.66 [95% CI, 0.49-0.89]; all P < .05) and
      by 45% versus reslizumab in the 400 cells/MUL or greater subgroup (rate ratio,
      0.55 [95% CI, 0.36-0.85]; P = .007). Asthma control was significantly improved
      with mepolizumab versus benralizumab (all subgroups: P < .05) and versus
      reslizumab in the 400 cells/MUL or greater subgroup (P = .004). Benralizumab
      significantly improved lung function versus reslizumab in the 400 cells/MUL or
      greater subgroup (P = .025). CONCLUSIONS: This ITC of the licensed doses suggests
      that mepolizumab was associated with significantly greater improvements in
      clinically significant exacerbations and asthma control compared with reslizumab
      or benralizumab in patients with similar blood eosinophil counts.

PMID- 30205190
TI  - Treatment of verrucous carcinoma in penis with topical aminolevulinic acid
      photodynamic therapy: An effective and safe treatment method.
AB  - BACKGROUND: Verrucous carcinoma of the penis is a rare disease characterized by
      verrucous lesions. The traditional treatment methods for verrucous carcinoma
      result in loss of sexual function are not satisfactory. The purpose of this study
      was to evaluate the safety and effect of topical aminolevulinic acid photodynamic
      therapy in the treatment of verrucous carcinoma in penis. MATERIALS AND METHODS:
      In this study, four male patients, average age of (47 +/- 7.58) years old, with
      penile verrucous carcinoma were treated with topical aminolevulinic acid
      photodynamic therapy (ALA-PDT) combined with curettage. First, the lesions were
      removed under local anesthesia. Then, the first session of PDT was performed
      right away. Ten percent 5-ALA cream was applied to surface of the lesions with
      occlusive dressing for a 3-h incubation period and the lesions were irradiated
      for 10 min by using a 635-nm laser beam of 177 mW/cm2 intensity. The ALA-PDT was
      repeated after 1 and 3 weeks and two other treatments applied if necessary.
      RESULTS: Three patients were cured by this treatment, with one case relapsed at 3
      months. There was no other recurrence at 5 years off treatments. The satisfaction
      rate of patients was 75% at 3 months after treatments. CONCLUSIONS: Topical PDT
      can be an effective and successful treatment modality for verrucous carcinoma in
      penis.

PMID- 30205191
TI  - Is There an Overlap in Immune Response Between Allergic Bronchopulmonary and
      Chronic Pulmonary Aspergillosis?
AB  - BACKGROUND: Chronic pulmonary aspergillosis (CPA) and allergic bronchopulmonary
      aspergillosis (ABPA) are presumed to represent 2 distinct manifestations of
      Aspergillus species in the lung. OBJECTIVE: To investigate any possible overlap
      of the immunological tests used for diagnosing ABPA in proven cases of CPA.
      METHODS: In consecutive subjects with CPA, we calculated the proportion of
      subjects who tested positive for all the immunological investigations used to
      diagnose ABPA (Aspergillus fumigatus specific IgE >0.35 kUA/L, total IgE >=500
      IU/mL, and eosinophil count >=500 cells/MUL) or obligatory criteria (A. fumigatus
      specific IgE >0.35 kUA/L and total IgE >=500 IU/mL). RESULTS: A total of 269
      subjects (53.5% males) of CPA with the mean (standard deviation [SD]) age of 44.3
      (14.7) years were enrolled. The most common underlying disease was previously
      treated pulmonary tuberculosis (n = 230, 85.5%). Ninety-three (34.6%) subjects
      had total IgE >=500 IU/mL, whereas A. fumigatus specific IgE >0.35 kUA/L was seen
      in 112 (41.6%) subjects. Thirteen (4.8%) subjects met all the immunological
      criteria for ABPA, whereas 59 (21.9%) subjects met the obligatory criteria.
      Subjects meeting the obligatory criteria had significantly higher eosinophil
      count (P <= .0001), greater immediate cutaneous reactivity to Aspergillus antigen
      (CPA-others vs obligatory criteria, 9.8 +/- 13.9 vs 13.9 +/- 14.9 mm, P value =
      .048), higher A. fumigatus specific IgG (99.3 +/- 61.9 vs 122 +/- 66.6 mgA/L, P =
      .015), and greater number of fungal balls (0.9 +/- 0.7 [range, 0-3] vs 1.1 +/-
      0.9 [range, 0-4], P = .026) compared with those without. CONCLUSIONS:
      Approximately 5% of subjects with CPA fulfilled all the immunological criteria
      used for diagnosing ABPA, whereas 22% met the obligatory criteria for ABPA.
      Whether these patients would require a different management protocol requires
      further investigation.

PMID- 30205192
TI  - Candida auris: Epidemiology, risk factors, virulence, resistance, and therapeutic
      options.
AB  - Candida auris emerged as a pathogen resistant to multiple antifungal and has been
      associated with nosocomial outbreaks with high transmission capacity between
      hospitalized individuals. C. auris was first described in 2009, after being
      isolated from the external ear canal discharge of a patient in Japan. The
      difficulty in identification, incorrect use of antifungal drugs, and treatment
      failure are causes of high mortality. Since then, C. auris has been increasingly
      reported from East Asia to North America, with substantial fatalities and
      misidentification. This review aims at describing the epidemiology, virulence,
      risk factors, resistance, and therapeutic options in C. auris infections.

PMID- 30205193
TI  - Effects of phytogenic feed additive based on thymol, carvacrol and cinnamic
      aldehyde on body weight, blood parameters and environmental bacteria in broilers
      chickens.
AB  - The aim of this study was to evaluate whether a phytogenic feed additive (PFA)
      based on essential oils such as carvacrol, thymol and cinnamic aldehyde, could be
      considered a replacement for antimicrobials used as growth promoters in broiler
      chickens, as well as to investigate its effect on total bacterial count,
      biochemical profiles, meat quality and meat fatty acid profile. A total of 240
      broiler chicks were randomly distributed into 4 groups with 4 replicates of 15
      animals each, as follow: T1 (basal diet only; the control group), T2 (basal diet
      supplemented with zinc bacitracin), T3 (basal diet with 0.5% of the PFA), T4
      (basal diet with 1.0% of the PFA). The addition of 0.5% of the PFA improved live
      body weight of supplemented birds compared to the control group at 35 and 42 days
      of age, while the total bacterial count in the environment was reduced when 1.0%
      of the PFA was used. In addition, intestinal villi height and crypt depth
      suffered variations during the entire experiment in birds treated with both
      concentrations of the PFA and zinc bacitracin. Total erythrocyte counts were
      higher on days 14, 28 and 42 in both treated groups (PFA) compared to the control
      group, as well as hemoglobin content on days 28 and 42. On the other hand,
      leukocyte counts were lower on days 14, 28 and 42 due to reduced lymphocyte
      counts in both PFA treated groups compared to the control group. Serum levels of
      alanine aminotransferase (ALT) were lower in broilers fed with either
      concentration of PFA on day 14 of life, and the same was observed regarding
      aspartate aminotransferase (AST) in broiler treated with 0.5% of the PFA. Also,
      total protein and globulin levels were lower on days 14 and 28 in groups fed with
      phytogenic compared to the control group. Regarding meat quality, breast meat
      showed higher red intensity and shear force in groups fed with both
      concentrations of phytogenic compared to the control group, while weight loss by
      cooking was lower. Finally, 1.0% of phytogenic showed lower docosadienoic acid
      (C22:2) content in breast meat. In conclusion, results showed that the use of
      PFAs based on carvacrol and thymol may be considered an interesting alternative
      to increase broilers performance, replacing the use of antimicrobials as growth
      promoters, as well as an interesting alternative to reduce the total bacterial
      count in the environment of broiler chickens. Moreover, the diet containing
      phytogenic also showed hepaprotective effects but deserves attention regarding
      possible alterations on the immune response.

PMID- 30205194
TI  - RS sample: Can be guide for empirical treatment of haematological malignancy
      patients?
AB  - Neutropenia due to intensive chemotherapy in haematological malignancy patients
      leaves the host vulnerable and makes them susceptible to infections. Infections
      are the most important cause of morbidity and mortality especially in
      haematological malignancy and chemotherapy patients. In addition, the use of
      multiple or inappropriate antibiotics leads to the development of resistant
      microorganisms. Therefore, the choice of empirical treatment is of vital
      important in these patient groups. Escherichia coli, Acinetobacter baumannii and
      Klebsiella pneumoniae are among the most frequently isolated Gram negative
      bacteria in neutropenic patients. Rectal swab (RS) samples were obtained from
      haematological malignancy patients not yet on chemotherapy or have no infection
      on chemotherapy period, E. coli was isolated from these samples, and A. baumannii
      and K. pneumoniae colonization were investigated. Susceptibilities of bacteria
      against antibiotics used in empirical treatment and prophylaxis were determined
      by using Gradient test strips according to the EUCAST recommendation. All
      isolates were sensitive against colistin. The resistant rates of antibiotics were
      detected as 39.1%, 9.4%, 6.8%, 35.1%, 31%, 39.1% for ciprofloxacin, meropenem,
      imipenem, piperacillin-tazobactam, cefepime, ceftazidime respectively The clonal
      relationship between Gram negative bacteria of intestinal flora and infection
      agents of same patient was investigated by Pulsed-Field gel electrophoresis.
      Twenty-three of the 30 patients (76.6%) were found to have a clonal relationship
      between the bacterial isolates before and after infection. It was determined that
      it can be able to predict with RS samples about possible agents of infection and
      their antibiotic susceptibility patterns.

PMID- 30205195
TI  - A cross-sectional analysis of Zika virus infection in symptomatic and
      asymptomatic non-pregnant travellers: Experience of a European reference center
      during the outbreak in the Americas.
AB  - BACKGROUND: Zika virus (ZIKV) infection a concern to travellers because of
      potential sexual transmission and adverse pregnancy outcomes. OBJECTIVE: To
      describe our experience in diagnosing ZIKV in travellers returning from endemic
      territories. METHOD: Travellers were evaluated for ZIKV at our clinic in a 12
      month period during the outbreak, using ZIKV-specific RT-PCR and anti-ZIKV
      Immunoglobulin M/G ELISA when symptomatic, and ELISA only for asymptomatic
      travellers, preferably from 20 days after the last exposure. All positive ELISA
      results were subject to confirmation by Virus Neutralization Testing. We
      estimated post-test probabilities of ZIKV in asymptomatic travellers. RESULTS: Of
      462 travellers, 227 reported symptoms and 235 did not. Asymptomatic travellers
      had similar baseline characteristics, but were younger (median age 31 vs. 33
      years, p = 0.01) and had reproductive concerns more often (75.8% vs. 24.2%). ZIKV
      infection was confirmed in 49 cases: 46/227 (20.3%) were symptomatic and 3/235
      (1.3%) asymptomatic. Rash (positive likelihood ratio (LRP) 5.6) and
      conjunctivitis (LRP 10.8) predicted ZIKV infection. The post-test probability of
      a negative ELISA-result at 20-25 days was below 0.1%. CONCLUSION: ZIKV infection
      was frequent in symptomatic, but not in asymptomatic travellers. We consider
      negative ELISA results at 20-25 days after exposure a safe strategy to rule out
      ZIKV infection. Testing for ZIKV-specific antibodies within this timeframe could
      be particularly valuable in the management of returning travellers who wish to
      conceive.

PMID- 30205196
TI  - Advances in instrumentation and methodology for solid-state NMR of biological
      assemblies.
AB  - Many advances in instrumentation and methodology have furthered the use of solid
      state NMR as a technique for determining the structures and studying the dynamics
      of molecules involved in complex biological assemblies. Solid-state NMR does not
      require large crystals, has no inherent size limit, and with appropriate isotopic
      labeling schemes, supports solving one component of a complex assembly at a time.
      It is complementary to cryo-EM, in that it provides local, atomic-level detail
      that can be modeled into larger-scale structures. This review focuses on the
      development of high-field MAS instrumentation and methodology; including probe
      design, benchmarking strategies, labeling schemes, and experiments that enable
      the use of quadrupolar nuclei in biomolecular NMR. Current challenges facing
      solid-state NMR of biological assemblies and new directions in this dynamic
      research area are also discussed.

PMID- 30205197
TI  - Family factors mediate discrimination related stress and externalizing symptoms
      in rural Latino adolescents.
AB  - INTRODUCTION: Externalizing disorders are more prevalent in rural than urban
      settings and account for disproportionately high mental health service costs for
      rural adolescents. Although cultural stressors such as discrimination have been
      associated with externalizing problems in ethnic minority youth broadly, this
      relationship is understudied in Latinos, particularly those in rural settings.
      Further, though the associations of family processes such as familism and family
      conflict have been studied in relation to youth externalizing symptoms, whether
      these processes change in the face of adolescent discrimination stress remains
      unknown. METHODS: A moderated multiple mediation model was used to examine the
      association between perceived discrimination, externalizing symptoms, and the
      indirect effect of family factors (familism, and family conflict) in a large
      sample (n = 455) of rural Latino youth. We also evaluated whether indirect and
      direct effects of discrimination on externalizing symptoms differed in boys
      versus girls. RESULTS: Familism and family conflict each independently mediated
      the relationship between discrimination related stress and externalizing
      symptoms. However, discrimination had a direct effect on externalizing symptoms
      for boys only. In girls, this association held only when family factors were
      accounted for. Post-hoc analyses reveal that the moderating effect of sex on
      discrimination is driven by differences in rule-breaking behavior, as opposed to
      aggressive behavior. CONCLUSION: Findings suggest that discrimination is
      associated with changes in the family environment which in turn invoke elevated
      risk for externalizing problems. Further, family-focused interventions that
      address externalizing problems may be especially effective for adolescent girls.

PMID- 30205198
TI  - CORT0C04210 is required for Candida orthopsilosis adhesion to human buccal cells.
AB  - Candida orthopsilosis is a human fungal pathogen belonging to the Candida
      parapsilosis sensu lato species complex. C. orthopsilosis annotated genome
      harbors 3 putative agglutinin-like sequence (ALS) genes named CORT0B00800,
      CORT0C04210 and CORT0C04220. The aim of this study was to investigate the role
      played by CORT0C04210 (CoALS4210) in the virulence and pathogenicity of this
      opportunistic yeast. Heterozygous and null mutant strains lacking one or both
      copies of CoALS4210 were obtained using the SAT1-flipper cassette strategy and
      were characterized in in vitro, ex vivo and in vivo models. While no differences
      between the mutant and the wild-type strains were observed in in vitro growth or
      in the ability to undergo morphogenesis, the CoALS4210 null mutant showed an
      impaired adhesion to human buccal epithelial cells compared to heterozygous and
      wild type strains. When the pathogenicity of CoALS4210 mutant and wild type
      strains was evaluated in a murine model of systemic candidiasis, no statistically
      significant differences were observed in fungal burden of target organs. Since
      gene disruption could alter chromatin structure and influence transcriptional
      regulation of other genes, two independent CRISPR/Cas9 edited mutant strains were
      generated in the same genetic background used to create the deleted strains.
      CoALS4210-edited strains were tested for their in vitro growing ability, and
      compared with the deleted strain for adhesion ability to human buccal epithelial
      cells. The results obtained confirmed a reduction in the adhesion ability of C.
      orthopsilosis edited strains to buccal cells. These findings provide the first
      evidence that CRISPR/Cas9 can be successfully used in C. orthopsilosis and
      demonstrate that CoALS4210 plays a direct role in the adhesion of C.
      orthopsilosis to human buccal cells but is not primarily involved in the onset of
      disseminated candidiasis.

PMID- 30205199
TI  - Role of the small GTPase Rho1 in cell wall integrity, stress response, and
      pathogenesis of Aspergillus fumigatus.
AB  - Aspergillus fumigatus is a major pathogen of invasive pulmonary aspergillosis.
      The small GTPase, Rho1, of A. fumigatus is reported to comprise a potential
      regulatory subunit of beta-1,3-glucan synthase and is indispensable for fungal
      viability; however, the role of AfRho1 on the growth, cell wall integrity, and
      pathogenesis of A. fumigatus is still poorly understood. We constructed A.
      fumigatus mutants with conditional- and overexpression of Rho1 and found that
      defects of AfRho1 expression led to the reduction of beta-1,3-glucan and
      glucosamine moieties on the cell wall, with down-regulated transcription of genes
      in the cell wall integrity signaling pathway and a decrease of calcofluor white
      (CFW)-stimulated mitogen-activated protein kinase (MpkA) phosphorylation and
      cytoplasmic leakage compared to those of the wild-type strain (WT). In addition,
      down-regulation of AfRho1 expression caused much higher sensitivity of A.
      fumigatus to H2O2 and alkaline pH compared to that of WT. Decrease of AfRho1
      expression also attenuated the A. fumigatus pathogenicity in Galleria mellonella
      and inhibited conidial internalization into lung epithelial cells and
      inflammatory factor release. In contrast, overexpression of Rho1 did not alter A.
      fumigatus morphology, susceptibility to cell wall stresses, or pathogenicity
      relative to its parental strain. Taken together, our findings support AfRho1 as
      an essential regulator of the cell wall integrity, stress response, and
      pathogenesis of A. fumigatus.

PMID- 30205200
TI  - UmTea1, a Kelch and BAR domain-containing protein, acts at the cell cortex to
      regulate cell morphogenesis in the dimorphic fungus Ustilago maydis.
AB  - The spatial organization of a cell is crucial for distribution of cell components
      and for cell morphogenesis in all organisms. Ustilago maydis, a basidiomycete
      fungus, has a yeast-like and a filamentous form. The former buds once per cell
      cycle at one of the cell poles, and can use the same site repeatedly or choose a
      new site at the same pole or opposite pole. The filamentous form consists of a
      long apical cell with short septate basal compartments lacking cytoplasm. It
      grows at the apex and can reverse growth forming a new growth zone at the basal
      end. We are interested in understanding how these different morphologies are
      generated. Here we present identification and characterization of U. maydis Tea1,
      a homologue of the fission yeast cell end marker Tea1. We demonstrate that
      UmTea1, a Kelch domain protein, interacts with itself and is an important
      determinant of the site of polarized growth: tea1 mutants bud simultaneously from
      both cell poles and form bifurcate buds. UmTea1 also regulates septum
      positioning, cell wall deposition, cell and neck width, coordination of nuclear
      division and cell separation, and localization of sterol-rich membrane domains.
      Some of these functions are shared with UmTea4, another cell end marker. We show
      that Tea1::GFP localizes to sites of polarized or potential polarized growth and
      to the septation site in the yeast-like form. Additionally, localization of
      Tea1::GFP as rings along the filament suggests that the filament undergoes
      septation. We hypothesize that Tea1 may act as a scaffold for the assembly of
      proteins that determine the site of polarized growth.

PMID- 30205201
TI  - Transcriptome reveals involvement of immune defense, oxidative imbalance, and
      apoptosis in ammonia-stress response of the black tiger shrimp (Penaeus monodon).
AB  - Ammonia is a major aquatic environmental pollutant that negatively impacts shrimp
      health and commercial productivity. However, we currently do not fully understand
      the underlying molecular mechanisms of ammonia stress in shrimp. We therefore
      performed transcriptomic analysis of hepatopancreas from black tiger shrimp
      (Penaeus monodon) treated with ammonia-stress. We obtained 146,410,174 and
      115,241,048 clean reads for the control and treatment groups, respectively. A
      total of 64,475 unigenes with an average length of 1275 bp and a N50 value of
      2158 bp were assembled. A comparative transcriptome analysis identified 3462
      differentially expressed genes, 177 of which are highly homologous with known
      proteins in aquatic species. Most of these genes showing the expression changes
      were related to immune function. Some significantly down-regulated genes are
      involved in purine metabolism and other metabolic pathways, which suggests that
      purineolytic capacity is an ammonia detoxification process in P. monodon, and
      metabolic depression is a strategy to reduce shrimp exposure to ammonia.
      Additionally, ammonia stress altered the expression patterns of key apoptosis
      genes (Bcl-xL, PERK, caspase 7, and caspase 10), confirmed that ammonia-stress
      induce oxidative stress and eventually even apoptosis. We also found evidence for
      the involvement of antioxidant defense in response to oxidative imbalance, given
      the regulation of peroxiredoxin 1, SOD, and CAT under ammonia stress. In
      conclusion, our study clarifies shrimp defensive response to ammonia toxicity and
      should benefit efforts to breed more ammonia-tolerant varieties.

PMID- 30205202
TI  - Molecular characterization of minichromosome maintenance protein (MCM7) in Scylla
      paramamosain and its role in white spot syndrome virus and Vibrio alginolyticus
      infection.
AB  - The minichromosome maintenance protein (MCM7) is a member of the MCM protein
      family which participates in the MCM complex by playing a role in the cell
      replication cycle and chromosome initiation in eukaryotes. The 2270 bp cDNA
      sequence of MCM7, including a 2127-bp open reading frame (ORF) encoding a 709-aa
      protein, was cloned from Scylla paramamosain using RT-PCR and RACE. Data showed
      that MCM7 was highly expressed in the digestive organ and hepatopancreas of S.
      paramamosain. Furthermore, MCM7 expression was down-regulated by infection with
      white spot syndrome virus (WSSV) or Vibrio alginolyticus. When MCM7 was knocked
      down, immune genes such as Janus kinase (JAK) and crustin antimicrobial peptide
      (CAP) were down-regulated, and C-type-lectin (CTL) was up-regulated in hemocytes.
      The mortality of WSSV-infected or V. alginolyticus-infected crabs was enhanced
      following MCM7 knockdown. It was demonstrated that MCM7 is very important in the
      progression of WSSV and V. alginolyticus infection. We also investigated the
      effect of MCM7 on apoptosis rate and phagocytic rate in S. paramamosain. MCM7
      knockdown caused higher levels of apoptosis in the hemocytes of the control,
      WSSV, and V. alginolyticus groups. MCM7 knockdown influenced the activity of
      phenoloxidase (PO) and superoxide dismutase (SOD), and total hemocyte count (THC)
      after infection with WSSV or V. alginolyticus, which indicated that MCM7 plays a
      regulatory role in innate immunity of crabs. Thus, we conclude that MCM7 may
      participate in the anti-WSSV and V. alginolyticus immune response in crabs by
      regulating apoptosis and the activity of PO and SOD.

PMID- 30205203
TI  - Biofloc technology (BFT): An alternative aquaculture system for prevention of
      Cyprinid herpesvirus 2 infection in gibel carp (Carassius auratus gibelio).
AB  - Gibel carp (Carassius auratus gibelio), a major aquaculture species in China, has
      emerged in a seriously epizootic disease caused by Cyprinid herpesvirus 2 (CyHV
      2). There are no effective methods to prevent or control this serious disease.
      Biofloc technology (BFT) can improve water quality, reduce pathogens
      introduction, enhance cultured species immunity and disease resistance. In this
      study, a 30-day experiment was conducted to investigate the effect of BFT on
      innate immune response and disease resistance of gibel carp against CyHV-2
      infection. Gibel carp was cultured at different total suspended solid (TSS)
      concentrations of 10, 300, 600, 800 and 1000 mg L-1, which were named as groups
      BF0, BF300, BF600, BF800 and BF1000. Results showed that fish in groups BF600/800
      had significantly higher weight gain (WG) and specific growth rate (SGR) than
      them in control group (BF0). The transcriptional levels of seven immune-related
      genes in BF300/600/800 groups, including myeloid-specific- peroxidase (MPO),
      keratin 8 (KRT 8), dual specificity phosphatase 1 (DUSP 1), interleukin-11 (IL
      11), intelectin (ITLN), purine nucleoside phosphorylase 5alpha (PNP 5alpha) and c
      type lysozyme (c-lys), were up-regulated significantly compared to BF0 group.
      Furthermore, cumulative mortality of gibel carp in BF600 group after being
      challenged with CyHV-2 reduced significantly. In vivo viral replication in kidney
      demonstrated that CyHV-2 load at 168 h post injection in BF600 group was
      significantly higher than that in BF0 group. In conclusion, BFT could improve
      growth, immune response and disease resistance of gibel carp, and the effect was
      related with TSS concentration. The optimal TSS concentration of 600-800 mg L-1
      was recommended in the present study.

PMID- 30205204
TI  - Identification and functional characterization of three myeloid differentiation
      factor 88 (MyD88) isoforms from thick shell mussel Mytilus coruscus.
AB  - Myeloid differentiation factor 88 (MyD88) is a pivotal adapter protein that
      involved in interleukin-1 receptor/toll-like receptor (IL-1R/TLR) signal
      transduction, which could spur downstream cascades and eventually drawn into
      innate immune response. MyD88 has been extensively studied in vertebrates,
      however, the information ascribe to MyD88 in invertebrates is still very scarce
      especially its function annotation remains extremely obscure. At here, three
      novel MyD88 isoforms termed McMyD88a, McMyD88b and McMyD88c were firstly cloned
      from thick shell mussel Mytilus coruscus. McMyD88a, McMyD88b and McMyD88c shared
      domain topology containing the Death domain (DD) and TIR domain (TIR) with its
      counterparts in mammals. All three McMyD88s were ubiquitously expressed in
      examined tissues in thick shell mussel, with the higher expression levels in
      immune-related tissues such as haemocytes, gills and digestive glands. Upon
      Vibrio alginolyticus, polyinosine-polycytidylic acid (poly I:C) and
      lipopolysaccharide (LPS) challenge, McMyD88a, McMyD88b and McMyD88c transcripts
      were significantly induced in haemocytes despite of differential expression
      levels and responsive time points. Overexpression of McMyD88a, McMyD88b and
      McMyD88c showed a dose-dependent induction to NF-kappaB or ISRE in mammalian cell
      lines. Taken together, these results suggested that McMyD88a, McMyD88b and
      McMyD88c are members of MyD88 family and play potential roles in innate immune
      response to pathogenic invasions in thick shell mussel. Moreover, these results
      suggested indirectly the existence of a MyD88-dependent signaling pathway in
      thick shell mussel, and provide insight into the immunoregulatory effect in
      molluscs.

PMID- 30205205
TI  - Rapamycin and fingolimod modulate Treg/Th17 cells in experimental autoimmune
      encephalomyelitis by regulating the Akt-mTOR and MAPK/ERK pathways.
AB  - Rapamycin prevents experimental autoimmune encephalomyelitis (EAE) and activates
      the MAPK/ERK pathway in EAE. Thus, we hypothesized combining rapamycin and
      fingolimod treatments would have synergistic effects in EAE. We show that
      combination therapy ameliorated EAE and regulated spinal cord IL-17 and TGF-beta
      levels in EAE mice. Combination therapy also modulated IL-17 and TGF-beta
      concentration, RoRgammat and Foxp3 mRNA levels, and Th17 cell and Treg
      frequencies in the spleen. Moreover, rapamycin decreased ps6k and increased pAkt
      and pERK, while combination therapy downregulated pAkt, ps6 k and pERK in EAE
      mice. Our findings provide insight into using this drug combination to treat EAE.

PMID- 30205206
TI  - Retrospective harmonization of multi-site diffusion MRI data acquired with
      different acquisition parameters.
AB  - A joint and integrated analysis of multi-site diffusion MRI (dMRI) datasets can
      dramatically increase the statistical power of neuroimaging studies and enable
      comparative studies pertaining to several brain disorders. However, dMRI data
      sets acquired on multiple scanners cannot be naively pooled for joint analysis
      due to scanner specific nonlinear effects as well as differences in acquisition
      parameters. Consequently, for joint analysis, the dMRI data has to be harmonized,
      which involves removing scanner-specific differences from the raw dMRI signal. In
      this work, we propose a dMRI harmonization method that is capable of removing
      scanner-specific effects, while accounting for minor differences in acquisition
      parameters such as b-value, spatial resolution and number of gradient directions.
      We validate our algorithm on dMRI data acquired from two sites: Philadelphia
      Neurodevelopmental Cohort (PNC) with 800 healthy adolescents (ages 8-22 years)
      and Brigham and Women's Hospital (BWH) with 70 healthy subjects (ages 14-54
      years). In particular, we show that gender and age-related maturation differences
      in different age groups are preserved after harmonization, as measured using
      effect sizes (small, medium and large), irrespective of the test sample size.
      Since we use matched control subjects from different scanners to estimate scanner
      specific effects, our goal in this work is also to determine the minimum number
      of well-matched subjects needed from each site to achieve best harmonization
      results. Our results indicate that at-least 16 to 18 well-matched healthy
      controls from each site are needed to reliably capture scanner related
      differences. The proposed method can thus be used for retrospective harmonization
      of raw dMRI data across sites despite differences in acquisition parameters,
      while preserving inter-subject anatomical variability.

PMID- 30205208
TI  - Comparing the potential of MEG and EEG to uncover brain tracking of speech
      temporal envelope.
AB  - During connected speech listening, brain activity tracks speech rhythmicity at
      delta (~0.5 Hz) and theta (4-8 Hz) frequencies. Here, we compared the potential
      of magnetoencephalography (MEG) and high-density electroencephalography (EEG) to
      uncover such speech brain tracking. Ten healthy right-handed adults listened to
      two different 5-min audio recordings, either without noise or mixed with a
      cocktail-party noise of equal loudness. Their brain activity was simultaneously
      recorded with MEG and EEG. We quantified speech brain tracking channel-by-channel
      using coherence, and with all channels at once by speech temporal envelope
      reconstruction accuracy. In both conditions, speech brain tracking was
      significant at delta and theta frequencies and peaked in the temporal regions
      with both modalities (MEG and EEG). However, in the absence of noise, speech
      brain tracking estimated from MEG data was significantly higher than that
      obtained from EEG. Furthemore, to uncover significant speech brain tracking,
      recordings needed to be ~3 times longer in EEG than MEG, depending on the
      frequency considered (delta or theta) and the estimation method. In the presence
      of noise, both EEG and MEG recordings replicated the previous finding that speech
      brain tracking at delta frequencies is stronger with attended speech (i.e., the
      sound subjects are attending to) than with the global sound (i.e., the attended
      speech and the noise combined). Other previously reported MEG findings were
      replicated based on MEG but not EEG recordings: 1) speech brain tracking at theta
      frequencies is stronger with attended speech than with the global sound, 2)
      speech brain tracking at delta frequencies is stronger in noiseless than noisy
      conditions, and 3) when noise is added, speech brain tracking at delta
      frequencies dampens less in the left hemisphere than in the right hemisphere.
      Finally, sources of speech brain tracking reconstructed from EEG data were
      systematically deeper and more posterior than those derived from MEG. The present
      study demonstrates that speech brain tracking is better seen with MEG than EEG.
      Quantitatively, EEG recordings need to be ~3 times longer than MEG recordings to
      uncover significant speech brain tracking. As a consequence, MEG appears more
      suited than EEG to pinpoint subtle effects related to speech brain tracking in a
      given recording time.

PMID- 30205209
TI  - Neural correlates of the energetic value of food during visual processing and
      response inhibition.
AB  - Previous research showed that human brain regions involved in reward and
      cognitive control are responsive to visually presented food stimuli, in
      particular high-energy foods. However, it is still to be determined whether the
      preference towards high-energy foods depends on their higher energy density
      (kcal/gram), or is based on the difference in energy content of the food items
      (total amount of kcal). Here we report the results of an fMRI study in which
      normal-weight healthy participants processed food images during a one-back task
      or were required to inhibit their response towards food stimuli during a Go/No-Go
      task. High-energy density (HD) and low-energy density (LD) foods were matched for
      energy content displayed. Food-related kitchen objects (OBJ) were used as control
      stimuli. The lateral occipital complex and the orbitofrontal cortex showed
      consistent higher activity in response to HD than LD foods, both during visual
      processing and response inhibition. This result suggests that images of HD foods,
      even when the amount of food shown is not associated with a higher energy
      content, elicit preferential visual processing - possibly involving attentional
      processes - and trigger a response from the reward system. We conclude that the
      human brain is able to distinguish food energy densities of food items during
      both active visual processing and response inhibition.

PMID- 30205207
TI  - Resting-state white matter-cortical connectivity in non-human primate brain.
AB  - Numerous studies have used functional magnetic resonance imaging (fMRI) to
      characterize functional connectivity between cortical regions by analyzing
      correlations in blood oxygenation level dependent (BOLD) signals in a resting
      state. However, to date, there have been only a handful of studies reporting
      resting state BOLD signals in white matter. Nonetheless, a growing number of
      reports has emerged in recent years suggesting white matter BOLD signals can be
      reliably detected, though their biophysical origins remain unclear. Moreover,
      recent studies have identified robust correlations in a resting state between
      signals from cortex and specific white matter tracts. In order to further
      validate and interpret these findings, we studied a non-human primate model to
      investigate resting-state connectivity patterns between parcellated cortical
      volumes and specific white matter bundles. Our results show that resting-state
      connectivity patterns between white and gray matter structures are not randomly
      distributed but share notable similarities with diffusion- and histology-derived
      anatomic connectivities. This suggests that resting-state BOLD correlations
      between white matter fiber tracts and the gray matter regions to which they
      connect are directly related to the anatomic arrangement and density of WM
      fibers. We also measured how different levels of baseline neural activity,
      induced by varying levels of anesthesia, modulate these patterns. As anesthesia
      levels were raised, we observed weakened correlation coefficients between
      specific white matter tracts and gray matter regions while key features of the
      connectivity pattern remained similar. Overall, results from this study provide
      further evidence that neural activity is detectable by BOLD fMRI in both gray and
      white matter throughout the resting brain. The combined use of gray and white
      matter functional connectivity could also offer refined full-scale functional
      parcellation of the entire brain to characterize its functional architecture.

PMID- 30205210
TI  - The BOLD response in primary motor cortex and supplementary motor area during
      kinesthetic motor imagery based graded fMRI neurofeedback.
AB  - There is increasing interest in exploring the use of functional MRI neurofeedback
      (fMRI-NF) as a therapeutic technique for a range of neurological conditions such
      as stroke and Parkinson's disease (PD). One main therapeutic potential of fMRI-NF
      is to enhance volitional control of damaged or dysfunctional neural nodes and
      networks via a closed-loop feedback model using mental imagery as the catalyst of
      self-regulation. The choice of target node/network and direction of regulation
      (increase or decrease activity) are central design considerations in fMRI-NF
      studies. Whilst it remains unclear whether the primary motor cortex (M1) can be
      activated during motor imagery, the supplementary motor area (SMA) has been
      robustly activated during motor imagery. Such differences in the regulation
      potential between primary and supplementary motor cortex are important because
      these areas can be differentially affected by a stroke or PD, and the choice of
      fMRI-NF target and grade of self-regulation of activity likely have substantial
      influence on the clinical effects and cost effectiveness of NF-based
      interventions. In this study we therefore investigated firstly whether healthy
      subjects would be able to achieve self-regulation of the hand-representation
      areas of M1 and the SMA using fMRI-NF training. There was a significant decrease
      in M1 neural activity during fMRI-NF, whereas SMA neural activity was increased,
      albeit not with the predicated graded effect. This study has important
      implications for fMRI-NF protocols that employ motor imagery to modulate activity
      in specific target regions of the brain and to determine how they may be tailored
      for neurorehabilitation.

PMID- 30205212
TI  - Human Genetics and Molecular Mechanisms of Congenital Hydrocephalus.

PMID- 30205211
TI  - Anterior Lumbar Interbody Fusion Using Reaction Bonded Silicon Nitride Implants:
      Long-Term Case Series of the First Synthetic Anterior Lumbar Interbody Fusion
      Spacer Implanted in Humans.
AB  - BACKGROUND: In this study, a historical case series is reported of reaction
      bonded silicon nitride (Si3N4) implants for anterior lumbar interbody fusion
      (ALIF) for a patient population of 30 and surgery levels L3/4, L4/5, and/or
      L5/S1. Before the study, the only work on Si3N4 as a biomedical material was
      associated preliminary work, which involved animal trials using a rabbit model.
      The objective was to undertake the first use of Si3N4 as a biomedical material
      for humans, as an implant for ALIF. METHODS: The Si3N4 implants were prepared by
      die-pressing silicon powder and reaction bonding in 95 N2/5 H2 at ~1400 degrees C
      for ~50 hours. The surgeries involved a retroperitoneal approach for L3/4 and
      L4/5 levels and a transperitoneal approach for L5/S1 level. The patient follow-up
      involved assessment of radiologic fusion up to 30 years and clinical outcomes to
      10 years. RESULTS: The reaction bonded Si3N4 implants were found to be
      biologically safe and to show high fusion rates with minimal subsidence, no
      abnormal reaction, and no other complications. The primary outcome measure,
      visual analog scale back pain, improved from a preoperative mean of 8.4 (range, 6
      10) to a mean of 3.7 (range, 0-9) at 5 years and a mean of 4.9 (range, 0-9) at 10
      years. The Oswestry Disability Index improved from a preoperative mean of 48
      (range, 26-84) to a mean of 35 (range, 4-76) at 10 years. CONCLUSIONS: This study
      confirms that Si3N4 is biologically safe in the long-term, with capacity for
      excellent radiologic osseointegration.

PMID- 30205214
TI  - Bouffant Versus Skull Cap: Does Operating Room Headwear Really Matter?

PMID- 30205213
TI  - Intracranial Nonskull-Based Chondrosarcoma Arising from the Sagittal Sinus: A
      Case Report and Review of the Literature.
AB  - BACKGROUND: Intracranial nonskull-based chondrosarcoma is a very rare malignant
      tumor. In fact, it is difficult to diagnose because of its atypical radiologic
      and morphologic features. We report a case of an intracranial parasagittal
      chondrosarcoma in the left parietal lobe accompanied with significant peritumoral
      edema (an extremely rare phenomenon for this tumor), with a review of the
      literature, to clarify aspects in the diagnosis of this rare tumor. METHODS: A
      literature search was using PubMed with specific key terms, inclusion criteria,
      and exclusion criteria. Selected case studies and case series were then compared
      and summarized them in Table 1. A 59-year-old male patient presented with a
      history of progressive right hemiparesis and loss of sensation for 45 days.
      RESULTS: Magnetic resonance imaging revealed a 2.6 * 2.4 * 2.8-cm mass arising
      from the superior sagittal sinus in his left parietal lobe. A left parietal
      parasagittal craniotomy was performed, and a macroscopically complete excision of
      the tumor was achieved. The patient recovered well postoperatively. Regular
      follow-up after 6 months revealed that he had almost recovered full strength to
      his right limbs, and there was no evidence of recurrence. Intracranial
      parasagittal chondrosarcoma in the parietal lobe is extremely rare. CONCLUSIONS:
      Although magnetic resonance imaging was performed, it is sometimes difficult to
      distinguish intracranial chondrosarcoma from meningioma and glioma, especially
      when the tumor arises from a nonskull base such as the meninges. Some cases could
      have significant peritumoral edema, although it is extremely rare. Histologic
      examination may aid in the diagnosis of this tumor. Neurosurgery is the most
      effective therapy for these tumors. Postoperative radiotherapy needs to be
      considered when the tumor is incompletely resected, has atypical histology, or is
      associated with significant peritumoral edema.

PMID- 30205215
TI  - Awake Craniotomy for Resection of Brain Metastases: A Systematic Review.
AB  - BACKGROUND: Surgery for brain metastases aims to reduce mass effect and achieve
      local control through maximizing resection. There is increasing recognition that
      awake craniotomy (AC) is especially relevant for resection of brain metastases in
      eloquent areas. This study seeks to examine the neurologic outcomes of using AC
      for brain metastases resection. METHODS: A systematic search for studies
      examining the role of AC in patients with brain metastases was conducted via
      PubMed without limitations on the year of publication, language, or study design,
      using the following search terms: (cerebral OR brain) and (metastases OR tumor)
      and (awake OR intraoperative OR eloquent OR supramarginal). Studies were included
      if patients underwent AC for resection of brain metastases and data on pre- and
      postoperative neurologic function were available. RESULTS: Seven studies
      published between 2001 and 2017 with 104 patients who underwent 107 ACs were
      identified. Gross total resection was achieved in 61% of patients, supramarginal
      resection was achieved in 32%, and subtotal resection was achieved in 7%.
      Immediately after operation, 73% of patients experienced no change or improvement
      in neurologic outcomes, whereas 27% experienced worsening. In the long term, 96%
      of those with postoperative worsening of function experienced improvements in
      neurologic function. CONCLUSIONS: Most patients experienced improvements in
      neurologic function immediately after AC, and most patients that experienced
      short-term worsening of neurologic function after the procedure showed excellent
      recovery. AC should be considered as a technique to optimize outcomes in brain
      metastases in eloquent areas.

PMID- 30205216
TI  - Dural Arteriovenous Fistula Formation Complicated Cerebral Venous Sinus Stenosis
      After Venous Sinus Stenting.
AB  - BACKGROUND: Venous stenting has become a promising treatment for venous sinus
      stenosis. However, it is not without its own set of risks. CASE DESCRIPTION: We
      reported de novo formation of dural arteriovenous fistula poststenting for venous
      sinus stenosis in a patient with pseudotumor cerebri. Multiple factors, including
      subclinical thrombus formation, sinus wall injury by stent placement, and up
      regulated inflammatory factors, may contribute to its pathogenesis. CONCLUSIONS:
      This case indicates that physicians may need to be aware of this rare
      complication, which can be managed without resumption of pseudotumor cerebri
      symptoms.

PMID- 30205217
TI  - Shunt Surgery for Neurocutaneous Melanosis with Hydrocephalus: Case Report and
      Review of the Literature.
AB  - BACKGROUND: Neurocutaneous melanosis is a rare phakomatosis characterized by
      large or multiple pigmented nevi and melanosis of the leptomeninges. It is often
      complicated by hydrocephalus due to melanotic deposits interfering with
      cerebrospinal fluid reabsorption in the basal cisterns or causing foraminal or
      aqueductal obstruction. In 10% of cases, it will be associated with the Dandy
      Walker complex. CASE DESCRIPTION: We present the case of a 6-year-old girl with
      multiple congenital hairy nevi presenting with generalized tonic-clonic seizures,
      headache, and vomiting. Neuroimaging showed a communicating hydrocephalus
      associated with the Dandy-Walker variant, melanotic deposits in the amygdalae,
      thalami, and cortical sulci, and abnormal leptomeningeal enhancement. After
      undergoing ventriculoperitoneal shunt insertion, the symptoms of increased
      intracranial pressure abated. However, she again showed deterioration 1 month
      postoperatively due to progressive leptomeningeal spread suspicious for malignant
      degeneration. CONCLUSION: The results of the present case and the findings from a
      review of related data suggest that shunt insertion (ventriculoperitoneal or
      cystoperitoneal) is an effective palliative measure for patients with
      neurocutaneous melanosis with associated hydrocephalus. Despite treatment,
      however, the prognosis of these patients remains poor owing to malignant
      progression and leptomeningeal spread of lesions, in particular, in cases
      associated with the Dandy-Walker complex.

PMID- 30205220
TI  - Skip Laminectomy Compared with Laminoplasty for Cervical Compressive Myelopathy:
      A Systematic Review and Meta-Analysis.
AB  - OBJECTIVE: This meta-analysis evaluated the clinical outcomes of skip laminectomy
      relative to laminoplasty for the treatment of cervical compressive myelopathy.
      METHODS: The Cochrane library, PubMed MEDLINE, EMBASE, and Web of Science
      databases were comprehensively searched to identify relevant articles published
      up to March 18, 2018. All values of weighted mean difference (WMD) or odds ratio
      are expressed as skip laminectomy relative to laminoplasty. RESULTS: Four studies
      comprising 241 patients were included. Skip laminectomy and laminoplasty were
      comparable in terms of cervical lordotic curvature (weighted mean difference
      [WMD] -2.37 degrees ; 95% confidence interval [CI] -6.18 to 1.43; P = 0.22) and
      range of motion (WMD -2.65 degrees ; 95% CI -6.02 to 0.72; P = 0.12). The pooled
      data revealed that the mean visual analogue scale score for pain of the skip
      laminectomy group was significantly lower than that of the laminoplasty group
      (WMD -0.97; 95% CI -1.90 to -0.05; P = 0.04), and the rate of axial pain was also
      significantly lower (WMD 0.26; 95% CI 0.07-0.93; P = 0.04). The atrophy rates of
      the deep extensor muscles in the skip laminectomy group (14%) were significantly
      lower than that of the laminoplasty group (60%). CONCLUSIONS: This meta-analysis
      determined that skip laminectomy was superior to laminoplasty in terms of visual
      analogue scale score and rates of axial pain and muscle atrophy. These results
      warrant further confirmation in future research.

PMID- 30205218
TI  - Impact of Functional Magnetic Resonance Imaging on Clinical Outcomes in a
      Propensity-Matched Low Grade Glioma Cohort.
AB  - BACKGROUND: This study aims to evaluate the impact of preoperative functional
      magnetic resonance imaging (fMRI) on clinical outcomes in patients with low grade
      glioma (LGG). METHODS: In a retrospective propensity-matched cohort study, we
      compared patients with LGG based on whether they underwent fMRI as part of
      preoperative assessment. Twelve patients with LGG who underwent preoperative fMRI
      were selected, and a contemporaneous group of 12 control patients with LGG who
      did not undergo fMRI were matched to the fMRI group based on age, sex, and 1p/19q
      status. RESULTS: fMRI group subjects tended to have more aggressive surgeries
      (67% resection, 33% biopsy) than the control group (33% resection, 67% biopsy).
      There were no significant differences in outcomes between the 2 groups. Time
      between clinical assessment and surgery tended to be longer in the fMRI group
      (6.3 +/- 4.2 weeks) than in the control group (2.7 +/- 2.2 weeks). Extent of
      resection was similar between the 2 cohorts. fMRI group subjects had lower
      preoperative functional status and tended to have a greater postoperative
      functional status improvement than control group subjects. Mean survival was not
      significantly different (fMRI group 5-year survival: 88.9%, control group 5-year
      survival: 61.1%). CONCLUSIONS: We evaluated the impact of preoperative fMRI in
      patients with LGG in this propensity-matched cohort study. This study has not
      demonstrated any significant difference in outcomes between the fMRI and control
      groups; however, there were nonsignificant trends for patients who underwent fMRI
      to undergo more aggressive surgical interventions and have a greater
      postoperative functional status improvement.

PMID- 30205219
TI  - Percutaneous Endoscopic Lumbar Discectomy Versus Posterior Open Lumbar
      Microdiscectomy for the Treatment of Symptomatic Lumbar Disc Herniation: A
      Systemic Review and Meta-Analysis.
AB  - OBJECTIVE: The purpose of this systematic review and meta-analysis was to compare
      the clinical efficacy between percutaneous endoscopic lumbar discectomy (PELD)
      versus posterior open lumbar microdiscectomy (OLMD) for the treatment of
      symptomatic lumbar disc herniation. METHODS: We performed a comprehensive
      retrieval of related studies in 4 electronic databases (PubMed, Embase, Web of
      Science, and the Cochrane Library). Randomized or nonrandomized controlled trials
      reported from January 1990 to December 2017 that compared PELD versus OLMD for
      the treatment of symptomatic lumbar disc herniation were acquired. The quality of
      randomized controlled trials was evaluated by the criteria of the Cochrane Back
      Review Group, and the quality of cohort studies was assessed according to the
      Newcastle-Ottawa Scale. The primary outcome measurements included preoperative
      and postoperative visual analog scale (VAS) score of sciatica; the Oswestry
      Disability Index (ODI) before and after surgery; the Excellent and Good outcome
      rate based on Macnab criteria. The secondary outcome measurements included the
      incidence of complication, residual disk, recurrence, and reoperation; operation
      time; hospital stay; and time to return to work. Two authors independently
      extracted data and assessed each study for quality. RESULTS: Nine studies with
      1585 patients were included in our meta-analysis. Two were randomized controlled
      trials and the remaining 7 were retrospective cohort studies. The forest plots
      showed that no statistically significant difference was observed between the 2
      groups in terms of preoperative and postoperative VAS score of sciatica, ODI
      before and after surgery, the Excellent and Good outcome rate, the complication
      rate, and the incidence of recurrence and reoperation. However, the PELD group
      had a higher incidence of residual disk or incomplete decompression than did the
      OLMD group. In addition, no significant difference was detected in the operation
      time between the 2 groups, but the PELD group was associated with shorter
      hospital stay and time of return to work. CONCLUSIONS: Based on the present meta
      analysis, no significant difference existed in VAS and ODI scores between the 2
      surgical procedures, and they were also similar in terms of operation time,
      complication rate, and incidence of recurrence and reoperation, but PELD showed
      shorter hospital stay and time of return to work. Thus, under the premise of
      careful manipulation and complete decompression, we consider that PELD is a
      relatively more minimally invasive technique, which could be an alternative to
      OLMD.

PMID- 30205221
TI  - Transcranial Magnetic Resonance-Guided Focused Ultrasound Surgery for Brain Tumor
      Ablation: Are We Ready for This Challenging Treatment?

PMID- 30205222
TI  - "Are You Going to Be in the Surgery?" How Residents Can Respond to Concerned
      Patients Based on "The Impact of Different Postgraduate Year Training in
      Neurosurgery Residency on 30-Day Outcomes" Studies.

PMID- 30205223
TI  - Malignant Transformation and Spine Metastasis of an Intracranial Grade I
      Meningioma: In Situ Immunofluorescence Analysis of Cancer Stem Cells Case Report
      and Literature Review.
AB  - BACKGROUND: Malignant meningiomas are rare neoplasms of the central nervous
      system that occur de novo or rarely as a result of transformation. They have a
      higher rate of recurrence and metastasis accompanied by a significantly shorter
      survivorship compared with benign variants. Meningioma cancer stem cells (CSCs)
      have been previously shown to be associated with resistance and aggressiveness.
      However, the role they play in meningioma progression is still being
      investigated. CASE DESCRIPTION: We report a 29-year-old man who underwent a
      resection of a grade I meningioma in 2011. The patient had multiple local
      recurrences of the tumor that showed an aggressive change in behavior and
      transformation to grade III meningioma, and developed extracranial metastasis to
      the cervical spine. He underwent multiple operations and received radiotherapy.
      Analysis of the tissues indicated the presence of CSC markers before metastasis,
      and showed increased expressions of associated markers in the metastasized
      tissue. In addition, similar to the patient's profile, the pharmacological
      testing of a primary cell line retrieved from the metastasized tissues showed a
      high level of drug tolerance and a diminished ability to initiate apoptosis.
      CONCLUSIONS: Malignant progression of grade I meningioma can occur, and its
      eventuality may be anticipated by detecting CSCs. We performed a comprehensive
      literature review of relevant cases and discussed the clinical, diagnostic, and
      management characteristics of the reported cases.

PMID- 30205224
TI  - An Early Description of Using Oral Route for the Management of Cervical Vertebra
      Fracture by Ibn al-Quff in the Thirteenth Century.
AB  - OBJECTIVE: This study presents information regarding the treatment of fractures
      and dislocations of the vertebrae, including the use of the oral route for upper
      cervical fractures, presented in certain chapters of the book titled Kitab al
      'Umda fi Sina'a al-Jiraha (Ibn al-Quff, thirteenth century ad). METHODS: A
      printed copy of the second volume of the book was studied. Chapters 22 ("On
      treatment of vertebral fractures") and 33 ("On treatment of vertebral
      dislocation") of the seventeenth treatise of this book were translated from
      Arabic into English. Each section is presented (in full text) in the Results
      section of this article. The findings were compared with the relevant literature
      and discussed to determine whether Ibn al-Quff presented novel information
      compared with that presented by his predecessors. RESULTS: The writings of Ibn al
      Quff regarding vertebral dislocations seem to summarize information derived from
      his predecessors. Moreover, he modified certain approaches, previously described
      for vertebral dislocations, and used them for correcting vertebral fractures. Ibn
      al-Quff introduced the most novel use of a bridlelike instrument for anterior
      cervical fracture through the oral route. By introducing the device in the mouth,
      he described a pushing maneuver to the cervical vertebrae from the ventral site
      and a simultaneous pulling maneuver by cupping on the neck from the dorsal site.
      CONCLUSIONS: The use of the oral route introduced by Ibn al-Quff may be one of
      the earliest examples of novel, practical, and advanced treatment for cervical
      vertebral fracture.

PMID- 30205225
TI  - Liponeurocytoma: Systematic Review of a Rare Entity.
AB  - OBJECTIVE: Liponeurocytoma is a rare benign tumor of the central nervous system,
      which develops mainly in adult patients within the posterior fossa. The World
      Health Organization has categorized this entity in its last classification of
      2016 as a benign grade II tumor. Histopathologic characteristics contain neuronal
      and variable astrocytic differentiation with foci of lipomatous distinction. Only
      a few case reports and case series have been reported and the knowledge of this
      tumor is limited. General treatment guidelines do not exist. The aim of this
      study was to analyze the literature to create treatment guidelines. METHODS:
      PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses)
      guidelines were followed to search existing online databases between January 1,
      1978 and May 15, 2018. RESULTS: A systematic review of the literature found 73
      patients (40 female, 33 male) with liponeurocytoma, in 59 of whom (80.8%) the
      disease occurred in the posterior fossa. The Ki-67/MIB-1 proliferation index was
      described in 58 patients, showing a mean value of 3.73% +/- 4.01%. Follow-up was
      performed in 49 patients, with a median length of 52.02 +/- 50.52 months, showing
      tumor recurrence in 14 patients (28.57%). Tumor recurrence was observed in only 1
      patient (1/12, 8.33%) after adjuvant radiotherapy, whereas tumor recurrence was
      seen in 13/29 patients (44.83%) who did not receive adjuvant radiotherapy.
      CONCLUSIONS: Liponeurocytomas are rare benign tumors, occurring mainly in the
      cerebellum. The therapy of choice is surgery. Postoperative radiotherapy seems to
      decrease the risk of tumor recurrence and should be offered to the patient.

PMID- 30205226
TI  - Price Transparency in Neurosurgery: Key Challenges and Proposed Solutions.

PMID- 30205227
TI  - Reiteration of "Less Invasive" Way and Graft Selections for Internal Maxillary
      Bypass.

PMID- 30205228
TI  - Treatment at Safety-Net Hospitals Is Associated with Delays in Coil Embolization
      in Patients with Subarachnoid Hemorrhage.
AB  - BACKGROUND: Successful endovascular management of aneurysmal subarachnoid
      hemorrhage (aSAH) requires timely access to substantial resources. Prior studies
      suggest an association between time to treatment and patient outcome. Patients
      treated at safety-net hospitals are thought to be particularly vulnerable to
      disparities in access to interventions that require substantial technologic
      resources. We hypothesized that patients with aSAH treated at safety-net
      hospitals are at greater risk for delayed access to endovascular treatment.
      METHODS: Adults undergoing endovascular coiling procedures between 2002 and 2011
      in the Nationwide Inpatient Sample were included. Hospitals in the quartile with
      the highest proportion of Medicaid or uninsured patients were defined as safety
      net hospitals. A multivariate model including patient-level and hospital-level
      factors was constructed to permit analysis of delays in endovascular treatment
      (defined as time to treatment >3 days). RESULTS: Analysis included 7109
      discharges of patients with aSAH undergoing endovascular coil embolization
      procedures from 2002 to 2011. Median time to coil embolization in all patients
      was 1 day; 10.1% of patients waited >3 days until treatment. In multivariate
      analysis, patients treated at safety-net hospitals were more likely to have a
      prolonged time to coil embolization (odds ratio = 1.32, P < 0.01) compared with
      patients treated at low-burden hospitals. CONCLUSIONS: After controlling for
      patient and hospital factors, individuals with aSAH treated at safety-net
      hospitals from 2002 to 2011 were more likely to have a delay to endovascular coil
      embolization than individuals treated at non-safety-net hospitals. This disparity
      could affect patient outcomes.

PMID- 30205230
TI  - Cord Haploidentical Non-In Vitro T Cell Depletion Allogeneic Hematopoietic Stem
      Cell Transplantation Reduces Relapse of Refractory Acute Leukemia.
AB  - Whether a graft-versus-graft (GVG) response in patients undergoing allogeneic
      hematopoietic stem cell transplantation (HSCT) is associated with an enhanced
      graft-versus-leukemia (GVL) effect remains highly controversial. Furthermore, it
      is unknown if the GVG response overwhelms the impact of refractory acute
      leukemia. We aimed to compare the characteristics and therapeutic outcomes
      between patients undergoing a modified haploidentical cord blood (cord-haplo)
      HSCT protocol (n = 97) and those undergoing haploidentical HSCT (n = 42) for
      refractory acute leukemia. A reliable and stable predominant haploidentical donor
      chimerism was established. The 2-year relapse rate was more favorable in patients
      undergoing cord-haplo HSCT than in those undergoing haploidentical HSCT (25.9%
      versus 53.2%; P = .007), as was progression-free survival (PFS; 35.5% versus
      17.9%; P = .049). Meanwhile, nonrelapse mortality at 2years was not significantly
      different (38.0% versus 24.6%; P = .367). We also found that a higher number of
      mutual haploidentical donor-mismatched antigens, a concept similar to HLA
      mismatching, was associated with better disease control. Multivariate analysis
      identified cord-haplo HSCT as an independent significant predictor of reduced
      relapse (hazard ratio [HR], .44; P = .028) and improved PFS (HR, .58; P = .033),
      as was chronic graft-versus-host disease (GVHD) (relapse: HR, .42; P  = .013;
      PFS: HR, .63: P = .052). However, the incidences of neutrophil and platelet
      engraftment, GVHD, and virus reactivation were comparable in the 2 groups. This
      study demonstrates that cord-haplo HSCT significantly enhances the GVL effect and
      improves PFS, providing a reliable and efficient therapeutic platform for
      patients with refractory acute leukemia.

PMID- 30205229
TI  - Wedge Hemivertebra Forward-Shifting Technique for Treatment of Congenital
      Kyphosis: Case Report, Technical Note, and Literature Review.
AB  - BACKGROUND: Congenital kyphosis due to wedge hemivertebra is an uncommon spinal
      deformity that could progressively develop into sagittal imbalance accompanied by
      subsequent neurologic deterioration if no intervention is performed. Numerous
      surgical techniques have been reported, since congenital kyphosis has shown no
      response to conservative treatments. Currently, osteotomy procedures, which are
      considered technically demanding and risky, have become the mainstream techniques
      for the correction of congenital kyphosis. METHODS: We describe the use of a
      novel surgical procedure combining forward-shifting of anterior column of the
      wedge hemivertebra and circumferential fusion for treatment of congenital
      kyphosis secondary to a wedge hemivertebra in a case of a 13-year-old boy who
      showed a 49 degrees  angular kyphosis from T12 to L2 secondary to a wedge
      hemivertebra in L1. RESULTS: The focal kyphosis was corrected to 5 degrees  with
      a correction rate of 89.8% after operation, and the sagittal balance was
      significantly preserved with no complication. Solid fusion was detected at the
      final follow-up. CONCLUSIONS: This novel procedure, combining forward-shifting of
      anterior column of the wedge hemivertebra and circumferential fusion, is a
      feasible, effective, and safe technique for the treatment of some special type 1
      congenital kyphosis cases, with a high correction rate and no major
      complications.

PMID- 30205231
TI  - Ruxolitinib Therapy Followed by Reduced-Intensity Conditioning for Hematopoietic
      Cell Transplantation for Myelofibrosis: Myeloproliferative Disorders Research
      Consortium 114 Study.
AB  - We evaluated the feasibility of ruxolitinib therapy followed by a reduced
      intensity conditioning (RIC) regimen for patients with myelofibrosis (MF)
      undergoing transplantation in a 2-stage Simon phase II trial. The aims were to
      decrease the incidence of graft failure (GF) and nonrelapse mortality (NRM)
      compared with data from the previous Myeloproliferative Disorders Research
      Consortium 101 Study. The plan was to enroll 11 patients each in related donor
      (RD) and unrelated donor (URD) arms, with trial termination if >=3 failures (GF
      or death by day +100 post-transplant) occurred in the RD arm or >=6 failures
      occurred in the URD. A total of 21 patients were enrolled, including 7 in the RD
      arm and 14 in the URD arm. The RD arm did not meet the predetermined criteria for
      proceeding to stage II. Although the URD arm met the criteria for stage II, the
      study was terminated owing to poor accrual and a significant number of failures.
      In all 19 transplant recipients, ruxolitinib was tapered successfully without
      significant side effects, and 9 patients (47%) had a significant decrease in
      symptom burden. The cumulative incidences of GF, NRM, acute graft-versus-host
      disease (GVHD), and chronic GVHD at 24 months were 16%, 28%, 64%, and 76%,
      respectively. On an intention-to-treat basis, the 2-year overall survival was 61%
      for the RD arm and 70% for the URD arm. Ruxolitinib can be integrated as
      pretransplantation treatment for patients with MF, and a tapering strategy before
      transplantation is safe, allowing patients to commence conditioning therapy with
      a reduced symptom burden. However, GF and NRM remain significant.

PMID- 30205232
TI  - Simultaneous quantitation of zidovudine, efavirenz, lopinavir and ritonavir in
      human hair by liquid chromatography-atmospheric pressure chemical ionization
      tandem mass spectrometry.
AB  - Nowadays, zidovudine, efavirenz, lopinavir and ritonavir are important components
      of the second-line antiretroviral therapeutic regimen of National Free
      Antiretroviral Treatment Program in China. The measurement of antiretroviral
      drugs in hair will facilitate for the evaluation of the long-term adherence to
      highly active antiretroviral therapy. Nevertheless, no study illustrated
      simultaneous quantitation of the four drugs in hair. The study intended to
      develop a simple, sensitive and selective method for simultaneous quantitation of
      the four drugs in hair. The detection employed high liquid chromatography tandem
      mass spectrometry with atmospheric pressure chemical ionization in positive mode.
      Hair samples were incubated in methanol at 40  degrees C for 16 h. The method
      showed the limit of detection at 18, 8, 5 and 6 pg/mg for zidovudine, efavirenz,
      lopinavir and ritonavir, respectively. The linear range (R2 > 0.99) was 36-5000
      pg/mg for zidovudine, 16-5000 pg/mg for efavirenz, 10-50,000 pg/mg for lopinavir
      and 12-12,500 pg/mg for ritonavir. The intra-day and inter-day coefficients of
      variation were <15% and the recovery varied from 88.1 to 110.5%. The population
      analysis revealed that patients with high adherence showed significantly higher
      drug concentrations in hair than those with low adherence for both AZT and EFV
      (ps < 0.05). There was high association in drug contents in hair between AZT and
      EFV or LPV and RTV (ps < 0.05).

PMID- 30205233
TI  - Chromatographic studies of chlorpropamide interactions with normal and glycated
      human serum albumin based on affinity microcolumns.
AB  - Sulfonylurea drugs have significant binding to proteins in blood, with most of
      this binding believed to occur with human serum albumin (HSA). High performance
      affinity chromatography and affinity microcolumns containing immobilized HSA were
      used to investigate binding by the sulfonylurea drug chlorpropamide to normal HSA
      and glycated HSA, which is a modified form of HSA that has an increased serum
      concentration in diabetes. Experiments employing frontal analysis indicated that
      the binding by chlorpropamide gave a good fit to a two-site model for both normal
      HSA and glycated HSA samples that were representative of controlled or advanced
      diabetes. These interactions involved a set of moderate-to-high affinity sites
      and a set of lower affinity sites, with binding constants in the range of 6.2-9.9
      * 104 M-1 and 0.18-0.57 * 104 M-1, respectively, at pH 7.4 and 37  degrees C.
      Competition studies utilizing a zonal elution format demonstrated that
      chlorpropamide could interact at both Sudlow sites I and II of HSA, with
      affinities in the range expected for the moderate-to-high affinity sites of this
      drug. The affinity of chlorpropamide at Sudlow site I had a small increase of up
      to 1.2-fold when comparing the normal HSA and glycated HSA samples.
      Chlorpropamide gave a larger 1.4- to over 1.5-fold increase at Sudlow site II
      when the affinity of this drug was compared between normal HSA and the same
      samples of glycated HSA. These results were compared to those obtained previously
      with other sulfonylurea drugs to help determine how glycation can change the
      overall and site-selective binding strength of these drugs with HSA at levels of
      protein modification that are seen in patients with diabetes.

PMID- 30205235
TI  - Signaling in electrical networks of the Venus flytrap (Dionaea muscipula Ellis).
AB  - The Venus flytrap captures insects with one of the most rapid movements in the
      plant kingdom. There is a significant difference between properties of electrical
      signals generated in the Venus flytrap described in literature. Amplitudes of
      action potentials vary from 14 mV to 200 mV with duration of signals from 2 ms to
      10 s. Here we present experimental study of potential differences between Ag/AgCl
      electrodes inserted to the trap, petiole, and into soil or external ECG
      electrodes attached to surfaces of the Venus flytrap. Diverse types of electrodes
      with various positions in a plant tissue or in soil show different amplitude and
      duration of electrical signals because potentials are measured in different
      electrochemical circuits. Electrical signals in the Venus flytrap were induced by
      mechanical stimulation of the trigger hairs or by chemical stimulation of a
      midrib using small drops of H2O2 or HNO3. Here we found that action potentials
      can propagate with speed up to 10 m/s in the trap of D. muscipula. Results are
      compared with equivalent electrical circuits.

PMID- 30205234
TI  - A sensitive LC-MS-MS assay for the determination of lapatinib in human plasma in
      subjects with end-stage renal disease receiving hemodialysis.
AB  - Most bioanalytical methods reported in literature for the quantitation of
      lapatinib in human plasma are either for lapatinib alone or lapatinib
      administered along with other tyrosine kinase inhibitors (TKIs) for therapeutic
      drug monitoring (TDM) in cancer patients. Recently there was a need for the
      quantitation of lapatinib in patients with end-stage renal disease (ESRD)
      receiving hemodialysis (HD). This special patient population normally receives
      many concomitant medications which have the potential to interfere with the
      quantitation of lapatinib. Here we describe an LC-MS-MS bioanalytical assay for
      the quantitation of lapatinib in human plasma containing potential concomitant
      medications which are commonly given to patients with ESRD receiving HD. The
      lapatinib calibration curve range was 2.50-1000 ng/mL. Lapatinib was fortified
      with its isotopically labeled internal standard in a 50 MUL plasma aliquot and
      extracted with protein precipitation. The chromatographic separation was achieved
      on a Zorbax SB-C18 (5 MUm, 2.1 * 50 mm) column with isocratic elution. Assay
      precision, accuracy, linearity, selectivity, sensitivity and analyte stability
      covering sample storage and analysis were established. No interferences were
      observed for the quantitation of lapatinib in the presence of concomitant
      medications. The validated LC-MS-MS method has been successfully applied to a
      clinical study for the determination of lapatinib concentrations in human plasma
      for patients with ESRD receiving HD.

PMID- 30205236
TI  - Effects of dietary lipid sources on hepatic nutritive contents, fatty acid
      composition and proteome of Nile tilapia (Oreochromis niloticus).
AB  - : Dietary oils of varying fatty acid composition have been used in tilapia feeds;
      nevertheless, investigation of their effects on metabolism and physiological
      processes has been limited. Therefore, in this study, using proteomic technology,
      the effects of different dietary lipids (DLs) on hepatic lipid metabolism and
      physiological processes were investigaed in Nile tilapia (Oreochromis niloticus).
      Fish were fed with different DL, which included palm oil (PO), linseed oil (LO)
      and soybean oil (SBO) for 90 days. Growth performance appeared to be similar
      among the dietary group. Hepatic FA contents were reflected by DL. Dietary PO
      (source of saturated fatty acids; SFA) led to an increase in the hepatosomatic
      index as well as lipid and protein contents in liver. Dietary SBO (source of n-6
      polyunsaturated fatty acids; n-6 PUFAs) increased hepatic carbohydrate contents,
      but decreased the hepatic protein. The proteomic analysis showed that these
      nutritive changes in the liver were mediated by several proteins involved in
      lipid, carbohydrate, and amino acid metabolism. Dietary SBO showed an increased
      accumulation in proteins related to oxidative stress, immune and inflammatory
      processes. Dietary LO (source of n-3 PUFAs) increased abundance of cytoskeleton
      related proteins. qRT-PCR was performed to provide supportive information for the
      result of proteomic study. Similar effects of DLs on mRNA levels were observed
      for atp5b, krt18, and selenbp1. Combined together, dietary SFA could supply as
      energy reservoir for regular activites. Dietary n-3 and n-6 PUFAs led to induce
      vital metabolic and physiologic processes which would contribute to maintaining
      normal health and/or providing health-related benefits. SIGNIFICANCE: Dietary SBO
      increased hepatic carbohydrate contents, but decreased the hepatic protein.
      Different dietary lipid led to alter the abundance of several proteins (i.e.,
      DHRS1, ATP5B, PLA2G12B, APO, AMY2A, GRP78, PRSS1, FAH, and PRSS36) involved in
      lipid, carbohydrate, and amino acid metabolism. Dietary SBO showed an increased
      accumulation in proteins (i.e., QDPR, CABC1, and PRDX6) that respond to oxidative
      stress, suggesting that n-6 PUFAs induce oxidative conditions. Dietary SBO led to
      increase the accumulation of proteins (i.e., NITR26, NCCRP1, and LCN) involved in
      immune and inflammatory processes. Dietary LO increased the abundant levels of
      cytoskeleton-related proteins (i.e., ACTB, AHNAK, ERC2, KRT18, and RILP1). Other
      proteins (i.e., SELENBP1, FAM46C, and ANC1) involved in other physiological
      processes were also modulated by DL. qRT-PCR was performed to provide supportive
      information of proteomic study. Similar effects of DLs on mRNA levels were
      observed for atp5b, krt18, and selenbp1.

PMID- 30205237
TI  - Venom characterization of the three species of Ophryacus and proteomic profiling
      of O. sphenophrys unveils Sphenotoxin, a novel Crotoxin-like heterodimeric beta
      neurotoxin.
AB  - : Venoms of the three species of Ophryacus (O. sphenophrys, O. smaragdinus, and
      O. undulatus), a viperid genus endemic to Mexico, were analyzed for the first
      time in the present work. The three venoms lacked procoagulant activity on human
      plasma, but induced hemorrhage and were highly lethal to mice. These venoms also
      displayed proteolytic and phospholipase A2 activities in vitro. The venom of O.
      sphenophrys was the most lethal and caused hind-limb paralysis in mice. Proteomic
      profiling of O. sphenophrys venom showed a predominance of metalloproteinase
      (34.9%), phospholipase A2 (24.8%) and serine protease (17.1%) in its composition.
      Strikingly, within its PLA2 components, 12.9% corresponded to a Crotoxin-like
      heterodimer, here named Sphenotoxin, which was not found in the other two species
      of Ophryacus. Sphenotoxin, like Crotoxin, is composed of non-covalently bound A
      and B subunits. Partial amino acid sequence was obtained for Sphenotoxin B and
      was similar (78-89%) to other subunits described. The mouse i.v. LD50 of
      Sphenotoxin at 1:1 M radio was 0.16 MUg/g. Also, like Crotoxin, Sphenotoxin
      induced a potent neuromuscular blockade in the phrenic nerve-diaphragm
      preparation. Ophryacus is the fifth genus and O. sphenophrys the third non
      rattlesnake species shown to contain a novel Crotoxin-like heterodimeric beta
      neurotoxin. BIOLOGICAL SIGNIFICANCE: Ophryacus is an endemic genus of semi
      arboreal pitvipers from Mexico that includes three species with restricted
      distributions. Little is known about the natural history of these species and
      nothing is known about the properties of their venoms. Research on these species'
      venoms could generate relevant information regarding venom composition of Mexican
      pitvipers. Additionally, research into the presence of neurotoxic Crotoxin-like
      molecules outside of rattlesnakes (genera Crotalus and Sistrurus) has identified
      this molecule in several new genera. Knowing which genera and species possess
      neurotoxic components is important to fully understand the repercussions of
      snakebites, the interaction with prey and predators, and the origin, evolution,
      and phylogenetic distribution of Crotoxin-like molecules during the evolutionary
      history of pitvipers. Our study expands current knowledge regarding venom's
      compositions and function from Mexican pitvipers, providing a comparative venom
      characterization of major activities in the three Ophryacus species.
      Additionally, the discovery and characterization of a novel Crotoxin-like
      molecule, here named Sphenotoxin, in O. sphenophrys, and the detailed protein
      composition of O. sphenophrys venom supports the hypotheses that Crotoxin-like 
      beta-neurotoxins are more widespread than initially thought.

PMID- 30205239
TI  - Erythropoietin (rhEPOa) promotes endothelial transdifferentiation of stem cells
      of the apical papilla (SCAP).
AB  - OBJECTIVE: Mesenchymal stem cells (MSCs) have attracted worldwide attention for
      their capacity to repair damaged tissue, immunosuppression, ability to
      differentiate into several cell types and their secretome. Earlier studies have
      demonstrated their angiogenic potential in vitro and in vivo. However, little is
      known regarding pro-angiogenic inducers of stable endothelial
      transdifferentiation of MSCs. Here, we employed human MSCs from the Apical
      Papilla (SCAP) and investigated whether recombinant human erythropoietin-alpha
      (rhEPOa) could act as such inducer. DESIGN: Cultured SCAP cells were exposed to
      rhEPOa and assessed for cell growth kinetics, viability and morphology, as well
      as their capacity to form capillary tubule structures in selected
      microenvironments. RT-PCR was used to monitor endothelial markers and activation
      of EPO/EPOR pathway signaling components; while gelatin zymographies to assess
      activation of MMP-2. RESULTS: rhEPOa treatment initially (48 h) accelerated cell
      proliferation and allowed SCAP to sprout micro-tubular structures. Morphological
      and biochemical differentiation was accompanied by activation of MMP-2 and
      upregulation of PECAM-1, VEGFR2, vWF and VE-cadherin/CDH5. SCAP expressed the
      cognate EPO-R, while rhEPOa-treated SCAP exhibited higher expression of molecules
      involved in EPO/EPOR pathway (EPOR and JAK2). CONCLUSION: rhEPOa is capable of
      promoting endothelial transdifferentiation of SCAP which may be of clinical value
      in treating of ischemic disorders.

PMID- 30205238
TI  - Protein expression in submandibular glands of young rats is modified by a high
      fat/high-sugar maternal diet.
AB  - OBJECTIVE: Maternal diet has consequences on many organs of the offspring, but
      salivary glands have received little attention despite the importance of the
      saliva secretory function in oral health and control of food intake. The
      objective of this work was therefore to document in rats the impact of maternal
      high-fat/high-sugar diet (Western Diet) on submandibular glands of the progeny.
      DESIGN: Sprague-Dawley rat dams were fed either a Western diet or control diet
      during gestation and lactation and their pups were sacrificed 25 days after
      birth. The pups' submandibular gland protein content was characterized by means
      of 2D-electrophoresis followed by LC-MS/MS. Data were further analyzed by Gene
      Ontology enrichment analysis and protein-protein interactions mapping. The
      expression of two specific proteins was also evaluated using
      immunohistochemistry. RESULTS: Combining both male and female pups (n = 18),
      proteome analysis revealed that proteins involved in protein quality control
      (e.g. heat shock proteins, proteasome sub-units) and microtubule proteins were
      over-expressed in Western diet conditions, which may translate intense metabolic
      activity. A cluster of proteins controlling oxidative stress (e.g. Glutathione
      peroxidases, peroxiredoxin) and enhancement of the antioxidant activity molecular
      function were also characteristic of maternal Western diet as well as under
      expression of annexin A5. The down-regulating effect of maternal Western diet on
      Annexin A5 expression was significant only for males (p < 0.05). CONCLUSIONS: A
      maternal Western diet modifies the protein composition of the offspring's
      salivary glands, which may have consequences on the salivary function.

PMID- 30205240
TI  - Protected area co-management and perceived livelihood impacts.
AB  - Creation of protected areas to conserve biodiversity can have both positive and
      negative impacts, with impacts unequally distributed within local communities. A
      global shift towards local community involvement in protected area governance and
      co-management has aimed to reduce costs of protected area establishment and their
      uneven distribution. Yet, there is mixed evidence to support whether such
      initiatives are succeeding. Here, a protected area in Madagascar is used as a
      case study to explore how co-management governance processes impact upon
      livelihood strategies and outcomes, and how these impacts are distributed within
      and between villages. Focus groups, interviews and questionnaires were conducted
      in 2015/16 with households surrounding a protected area, co-managed by local
      community associations and a national NGO. Data analysis was framed around the
      Sustainable Livelihoods Framework. The majority of respondents perceived negative
      livelihood outcomes, and impacts were unevenly distributed between social groups.
      Respondents were more likely to report negative livelihood outcomes if they were
      from remote villages, poorer households and reliant on provisioning ecosystem
      services before protected area establishment. Qualitative data showed that the
      main drivers of this were protected area-related rules and regulations
      restricting forest activities. Drivers of improved livelihood outcomes were
      training and materials improving agricultural yields and increased community
      cohesion. Although co-managed protected areas may be overall more effective in
      meeting biological and socio-economic goals than protected areas of other
      governance types, the evidence here suggests that governance processes can lead
      to local perceptions of inequity.

PMID- 30205241
TI  - Rationale and design of the Study of Dietary Intervention Under 100 MMOL in Heart
      Failure (SODIUM-HF).
AB  - BACKGROUND: Patients with heart failure (HF) remain at high risk for future
      events despite medical and device therapy. Dietary sodium reduction is often
      recommended based on limited evidence. However, it is not known whether dietary
      sodium reduction reduces the morbidity or mortality associated with HF. METHODS:
      The SODIUM study is a pragmatic, randomized, open-label trial assessing the
      efficacy of dietary sodium reduction to <1500 mg daily counseling compared to
      usual care for patients with chronic HF. The intervention is provided by trained
      personnel at the site and uses 3-day food records for directing counseling. The
      primary outcome is an intention-to-treat analysis on the time to first
      cardiovascular event or death measured at 12 months. Secondary end points include
      the change in quality of life (using the Kansas City Cardiomyopathy
      Questionnaire), change in New York Heart Association class, and change in 6
      minute walk test. The first patient was enrolled in March 2014, and subsequently,
      27 sites in 6 countries enrolled patients. CONCLUSIONS: The SODIUM-HF trial will
      provide a robust evaluation of the effects of dietary sodium reduction in
      patients with HF. Results are expected in 2020.

PMID- 30205242
TI  - Rational and design of the European randomized Optical Coherence Tomography
      Optimized Bifurcation Event Reduction Trial (OCTOBER).

PMID- 30205243
TI  - Minimum structural requirements for BMP-2-binding of heparin oligosaccharides.
AB  - Bone morphogenetic proteins (BMPs) are essential during tissue repair and
      remodeling after injury. Glycosaminoglycan (GAG) sugars are known to enhance BMP
      activity in vitro and in vivo; here the interactions of BMP-2 with various
      glycosaminoglycan classes were compared and shown to be selective for heparin
      over other comparable saccharides. The minimal chain lengths and specific sulfate
      moieties required for heparin-derived oligosaccharide binding to BMP-2, and the
      ability of such oligosaccharides to promote BMP-2-induced osteogenic
      differentiation in vitro were then determined. BMP-2 could bind to heparin
      hexasaccharides (dp6) and octasaccharides (dp8), but decasaccharides (dp10) were
      the minimum chain length required for both efficient binding of BMP-2 and
      consequent heparin-dependent cell responses. N-sulfation is the most important,
      and 6-O-sulfation moderately important for BMP-2 binding and activity, whereas 2
      O-sulfation was much less critical. Bone formation assays in vivo further
      confirmed that dp10, N-sulfated heparin oligosaccharides were the minimal
      requirement for effective enhancement of BMP-2-induced bone formation. Such
      information is necessary for the rational design of the next generations of
      heparan-based devices for bone tissue repair.

PMID- 30205244
TI  - Gold-copper nanoshell dot-blot immunoassay for naked-eye sensitive detection of
      tuberculosis specific CFP-10 antigen.
AB  - Herein, a straightforward and highly specific dot-blot immunoassay was
      successfully developed for the detection of Mycobacterium tuberculosis antigen
      (10 kDa culture filtrate protein, CFP-10) via the formation of copper nanoshell
      on the gold nanoparticles (AuNPs) surface. The principle of dot-blot immunoassay
      was based on the reduction of Cu2+ ion on the GBP-CFP10G2-AuNPs conjugates, which
      has gold binding and antigen binding affinities, simultaneously, favouring to
      appear red dot that can be observed with naked-eye. The dot intensity is
      proportional to the concentration of tuberculosis antigen CFP-10, which offers a
      detection limit of 7.6 pg/mL. The analytical performance of GBP-CFP10G2-AuNPs
      copper nanoshell dot-blot was superior than that of conventional silver
      nanoshell. This method was successfully applied to identify the CFP-10 antigen in
      the clinical urine sample with high sensitivity, specificity, and minimized
      sample preparation steps. This method exhibits great application potential in the
      field of nanomedical science for highly reliable point-of-care detection of CFP
      10 antigen in real samples to early diagnosis of tuberculosis.

PMID- 30205245
TI  - Repeated transfer enriches highly active electrotrophic microbial consortia on
      biocathodes in microbial fuel cells.
AB  - Cathodic oxygen reduction catalyzed by autotrophic bacteria instead of a precious
      metal is a promising method to make use of microbial fuel cells (MFCs) in
      wastewater treatment with electricity production. However, the ecology of
      electrotrophic microbial consortia in wastewater systems that function as the
      catalyst for cathodic oxygen reduction is complicated and the electron transfer
      mechanisms are still unknown, which prevents further improvements of the
      biocathode performance. Enriched by the repeated transfer of a mature
      electrotrophic microbial consortia to new cathodes over 10 generations in 230
      days, the start-up time was shortened from 21.4 to 7.6 days and the maximum
      current densities over the potential range of 0.5 to - 0.3 V increased by up to
      112%, from 75 +/- 5 A m-3 to 159 +/- 3 A m-3, which was further confirmed in half
      cell biocathode systems. The electrotrophic microbial consortia approached a
      relatively stable state after 8 generations. Acinetobacter, which is a member of
      Proteobacteria, was selectively enriched after 10 generations, which was closely
      related to the current production. Nitrospiraceae and Nitrosomonas may jointly
      perform a nitrogen cycling metabolic process and promote cathodic bioelectron
      transfer. Our findings confirmed that the electrotrophic microbial consortia on
      the cathode was able to be specifically evolved, leading to higher
      electroactivity, and also revealed which bacteria in fresh water are closely
      related to cathodic electron transfer.

PMID- 30205246
TI  - Recent uses of carbon nanotubes & gold nanoparticles in electrochemistry with
      application in biosensing: A review.
AB  - The innovation of nanoparticles assumes a critical part of encouraging and giving
      open doors and conceivable outcomes to the headway of new era devices utilized as
      a part of biosensing. The focused on the quick and legitimate detecting of
      specific biomolecules using functionalized gold nanoparticles (Au NPs), and
      carbon nanotubes (CNTs) has turned into a noteworthy research enthusiasm for the
      most recent decade. Sensors created with gold nanoparticles or carbon nanotubes
      or in some cases by utilizing both are relied upon to change the very
      establishments of detecting and distinguishing various analytes. In this review,
      we will examine the current utilization of functionalized AuNPs and CNTs with
      other synthetic mixes for the creation of biosensor prompting to the location of
      particular analytes with low discovery cutoff and quick reaction.

PMID- 30205247
TI  - 4,5-Diazafluorene N-glycopyranosyl hydrazones as scaffolds for potential
      bioactive metallo-organic compounds: Synthesis, structural study and cytotoxic
      activity.
AB  - A series of novel N1-(4,5-diazafluoren-9-yliden)-N2-glycopyranosyl hydrazines was
      prepared in synthetically useful yields by treatment of 9H-4,5-diazafluoren-9
      hydrazone with different unprotected monosaccharides. The reactions with the
      monosaccharides tested afforded stereoselectively, and exclusively, cyclic
      derivatives, whose structures correspond to N-beta-glycopyranosyl hydrazones
      except for the d-arabinose derivative that agrees with the alpha-anomer. Several
      copper(II) complexes having a 2:1 ligand to metal mole ratio were also prepared.
      The metal complexes can bind DNA sequences and preferentially stabilize G
      quadruplex DNA structures over dsDNA. The fucose, rhamnose and deoxyglucose
      copper(II) complexes exhibited a cytotoxic activity against cultured HeLa and PC3
      tumor cells comparable to other metal complexes normally used for
      chemotherapeutic purposes, such as cisplatin.

PMID- 30205249
TI  - Metacognitive knowledge of attention in children with and without ADHD symptoms.
AB  - Children with ADHD (Attention Deficit Hyperactivity Disorder) experience
      difficulty in managing attention in school, but it is not sufficiently clear what
      their attentional beliefs are. Drawing is a means of expression that is
      habitually used to access knowledge or ideas of children regarding their
      classroom experience. The aim of this study is to verify whether children with
      ADHD use pictorial indicators analogous to children without ADHD (N-ADHD). 92
      primary school students participated in this study, half of whom diagnosed with
      ADHD. Children were asked to produce two specific thematic drawings on attention
      vs. inattention; their pictorial representations were analyzed using the
      Children's Awareness of Attention through Drawing (CAAD). The analysis showed
      principally that children with ADHD have a metacognitive awareness of attention
      similar to N-ADHD except for a delay in acquisition of the correct posture, for
      less maturation in the management of school materials and greater expression of
      negative feelings over time. Children with ADHD are aware of what is required in
      the school context but they are not able to pursue it. Behavioral intervention
      and structured learning are two targets of intervention that can help children
      with ADHD to adapt and to stay at school.

PMID- 30205248
TI  - Toxic effects of nickel oxide (NiO) nanoparticles on the freshwater alga
      Pseudokirchneriella subcapitata.
AB  - Over the last decade, concerns have been raised regarding the potential health
      and environmental effects associated with the release of metal oxide
      nanoparticles (NPs) into ecosystems. In the present work, the potential hazards
      of nickel oxide (NiO) NPs were investigated using the ecologically relevant
      freshwater alga Pseudokirchneriella subcapitata. NiO NP suspensions in algal OECD
      medium were characterized with regard to their physicochemical properties:
      agglomeration, surface charge, stability (dissolution of the NPs) and abiotic
      reactive oxygen species (ROS) production. NiO NPs formed loose agglomerates and
      released Ni2+. NiO NPs presented a 72 h-EC50 of 1.6 mg L-1, which was evaluated
      using the algal growth inhibition assay and allowed this NP to be classified as
      toxic. NiO NPs caused the loss of esterase activity (metabolic activity), the
      bleaching of photosynthetic pigments and the intracellular accumulation of
      reactive oxygen species (ROS) in the absence of the disruption of plasma membrane
      integrity. NiO NPs also disturbed the photosynthetic process. A reduction in the
      photosynthetic efficiency (PhiPSII) accompanied by a decrease in the flow rate of
      electrons through the photosynthetic chain was also observed. The leakage of
      electrons from the photosynthetic chain may be the origin of the ROS found in the
      algal cells. The exposure to NiO NPs led to the arrest of the cell cycle prior to
      the first cell division (primary mitosis), an increase in cell volume and the
      presence of aberrant morphology in the algal cells. In this work, the use of
      different approaches allowed new clues related to the toxicity mechanisms of NiO
      NPs to be obtained. This work also contributes to the characterization of the
      environmental and toxicological hazards of NiO NPs and provides information on
      the possible adverse effects of these NPs on aquatic systems.

PMID- 30205250
TI  - Impact of perceived rearing and social support on bonding failure and depression
      among mothers: A longitudinal study of pregnant women.
AB  - BACKGROUND: Although previous studies have reported associations between bonding
      failure, depression, social support among mothers, and perceived rearing, the
      causal relationships remain unclear. METHODS: A total of 855 women (mean age,
      32.4 +/- 4.4 years) completed the Mother-Infant Bonding Questionnaire (MIBQ), the
      Edinburgh Postnatal Depression Scale (EPDS), the Japanese version of the Social
      Support Questionnaire, and the Parental Bonding Instrument in early pregnancy
      before week 25 (T1) and at 1 month after delivery (T2). We created a path model
      to clarify the causal relationships between perinatal bonding failure,
      depression, social support, and perceived rearing during pregnancy and at 1 month
      after delivery. The model was tested using structural equation modeling. RESULTS:
      Our recursive model showed acceptable fit (chi-squared statistic/degree of
      freedom = 2.1, comparative fit index = 0.98, root mean square error of
      approximation = 0.04). It was revealed that: (1) at T1, higher overprotection
      significantly predicted MIBQ scores; (2) at T1, poorer social support
      significantly predicted both MIBQ and EPDS scores; and (3) at T1, both MIBQ and
      EPDS scores significantly predicted respective scores at T2. CONCLUSIONS: These
      results showed that bonding failure in the postpartum period was significantly
      influenced by mothers' own perceived rearing and social support during pregnancy.
      In addition, depression in the postpartum period was strongly influenced by
      social support during pregnancy. These findings suggest that psychosocial
      interventions that focus on both mothers' recollections of their own upbringing
      and social support during pregnancy are effective for preventing bonding failure
      and depression in the postpartum period.

PMID- 30205251
TI  - Boosting charge transfer via molybdenum doping and electric-field effect in
      bismuth tungstate: Density function theory calculation and potential
      applications.
AB  - Regulating internal electronic structure of photocatalysts via elements doping
      holds huge potential in tuning efficient charge transfer and boosting high
      performance. Herein, molybdenum embedded bismuth tungstate (Bi2WO6) is employed
      to explore the electronic structures and various performances via the assistance
      of experimental verification and density function theory (DFT) simulation. The
      band structures and Mo ions doping behaviors of Bi2MoxW1-xO6 are systematically
      measured. Doping can induce the distortion of intrinsic electric density and
      internal electric-field, resulted in efficient charge transfer of Bi2Mo0.4W0.6O6.
      It exhibits much efficient photocatalytic activities under visible-light
      irradiation, also manifests huge potential as an anode material in lithium-ion
      batteries (LIBs) which is rarely reported before. This work may provide insights
      in the development of bismuth-based semiconductors in energy related
      applications.

PMID- 30205253
TI  - Effect of pH on photocatalytic and photoelectrochemical (PEC) properties of
      monoclinic bismuth vanadate.
AB  - Monoclinic bismuth vanadate (c-BVO) was prepared via simple calcination of
      solvothermally processed tetrahedral BiVO4. The physicochemical and morphological
      properties of c-BVO demonstrated the successful synthesis of the photoactive
      monoclinic phase from the tetrahedral phase, which has low photoactivity
      properties. The photoactivities of c-BVO were investigated using the
      photodegradation of methylene blue (MB) and photoelectrochemical (PEC)
      measurements in acidic (pH = 2.5), neutral (pH = 6.5) and basic (pH = 9.5) media.
      The photocatalytic activity of c-BVO was increased with increasing pH, achieved
      99% MB degradation in the basic condition, compared with 70 and 45% in the
      neutral and acidic media, respectively. Although the tetrahedral BiVO4 showed
      mainly adsorption with negligible photodegradation, c-BVO demonstrated both good
      adsorption and photodegradation activities. The PEC results indicated that the
      photocurrent density was affected by both pH and applied voltage. Impedance
      measurements showed faster charge transfer in the neutral condition than in the
      acidic and basic electrolytes. The incident photon conversion efficiency (IPCE)
      showed very low activity for tetrahedral BiVO4, but in comparison it was enhanced
      by 20- and 10-fold for c-BVO in the visible and simulated solar light,
      respectively.

PMID- 30205252
TI  - Stability of near-surface ordering of bicontinuous microemulsions in external
      shear-fields.
AB  - The lubrication effect of bicontinuous microemulsions describes a facilitated
      flow along hydrophilic planar surfaces because the fluid forms lamellar domains
      that can slide off along each other much better than randomly ordered domains.
      The applicability of this effect is based on the prerequisite of the lamellar
      structure not being destroyed by external shear-fields. In this paper, we
      demonstrate that the lamellar structure is highly stable for shear rates of up to
      600 s-1 using neutron reflectivity and grazing incidence small angle neutron
      scattering experiments. The transition structure that consists of perforated
      lamellae is attacked by the flow, and the bicontinuous microemulsion comes closer
      to the solid interface when shear is applied. All of this verifies the stability
      of the lubrication effect for technical applications.

PMID- 30205254
TI  - Silicon core-mesoporous shell carbon spheres as high stability lithium-ion
      battery anode.
AB  - An innovative and simple synthesis strategy of silicon nanoparticle (Si NP) core
      covered by mesoporous shell carbon (MSC) structure is demonstrated. The Si
      core@MSC (SCMSC) composite is developed for addressing the issues for Si anode
      material in lithium ion batteries (LIBs) such as high volume expansion and low
      electrical conductivity. Significant improvement in the electrochemical
      performance for the SCMSC anode is observed compared with bare Si anode. The
      SCMSC composite delivers an initial specific capacity of 2450 mAh g-1 at 0.166 A
      g-1 with Coulombic efficiency of 99.2% for 100 cycles. Compared to bare Si anode,
      the SCMSC anode exhibits much higher Li storage capacity, superior cyclability,
      and good rate capability, highlighting the advantages of hierarchical MSC in the
      SCMSC structure.

PMID- 30205255
TI  - Exploring individual and contextual factors contributing to tobacco cessation
      intervention implementation.
AB  - BACKGROUND: Previous research suggests that smoking cessation interventions are
      poorly implemented. This study reports the development and testing of a
      questionnaire including knowledge, attitude, behavioral, and organizational
      (KABO) factors affecting the implementation of smoking cessation practices in
      hospitals by health care providers and organizations. METHODS: An initial pool of
      44 items was developed to assess the individual knowledge, attitudes, and beliefs
      of health professionals towards smoking cessation practices according to the 5
      A's intervention model, as well as organizational barriers and opportunities for
      its implementation. Items were measured in a scale from 0="Not at all/Never" to
      10 = "Completely/Always". Data were collected from health workers (n = 702) in
      Catalonia. The validity of the instrument was measured by: (a) analyzing the
      items, (b) assessing the internal structure, (c) estimating the internal
      consistency, and (d) analyzing the relationship between this tool and the 5 A's
      intervention model. RESULTS: Seven domains were extracted: individual skills,
      positive organizational support, attitudes and beliefs, individual commitment,
      organizational resources, beliefs about patient desire/readiness to quit, and
      organizational endorsement. These domains explained 69.7% of the variance, and
      allowed for the development of a refined 26-item version of the questionnaire.
      Both the seven domains and the total scale showed adequate internal consistency.
      CONCLUSIONS: Psychometric testing indicates that the KABO questionnaire is a
      reliable and valid instrument for assessing the main barriers and facilitators to
      smoking cessation intervention implementation. Individual factors better
      explained the implementation of smoking cessation interventions in hospitals, and
      the seven identified domains can be used for further investigations into how the
      implementation of evidence-based practices impacts smoking cessation performance.

PMID- 30205257
TI  - Substance usage intention does not affect attentional bias: implications from
      Ecstasy/MDMA users and alcohol drinkers.
AB  - BACKGROUND: An attentional bias towards substance-related stimuli has been
      demonstrated with alcohol drinkers and many other types of substance user. There
      is evidence to suggest that the strength of an attentional bias may vary as a
      result of context (or use intention), especially within Ecstasy/MDMA users.
      OBJECTIVE: Our aim was to empirically investigate attentional biases by observing
      the affect that use intention plays in recreational MDMA users and compare the
      findings with that of alcohol users. METHOD: Regular alcohol drinkers were
      compared with MDMA users. Performance was assessed for each group separately
      using two versions of an eye-tracking attentional bias task with pairs of matched
      neutral, and alcohol or MDMA-related visual stimuli. Dwell time was recorded for
      alcohol or MDMA. Participants were tested twice, when intending and not intending
      to use MDMA or alcohol. Note, participants in the alcohol group did not complete
      any tasks which involved MDMA-related stimuli and vice versa. RESULTS:
      Significant attentional biases were found with both MDMA and alcohol users for
      respective substance-related stimuli, but not control stimuli. Critically, use
      intention did not affect attentional biases. Attentional biases were demonstrated
      with both MDMA users and alcohol drinkers when usage was and was not intended.
      CONCLUSIONS: These findings demonstrate the robust nature of attentional biases
      i.e. once an attentional bias has developed, it is not readily affected by
      intention.

PMID- 30205256
TI  - Evaluations of clinical tobacco cessation interventions in Arab populations: A
      systematic review.
AB  - BACKGROUND AND AIMS: Tobacco smoking is prevalent among Arab smokers.
      Interventions to support smoking cessation may differ in effectiveness in this
      population from Western populations usually studied. This review assessed
      evidence of effectiveness of clinical smoking interventions in Arab smokers.
      METHODS: A systematic search for comparative trials evaluating tobacco cessation
      interventions in Arab populations was conducted in the MEDLINE, EMBASE,
      PyschINFO, CINHAL and Web of Science databases. Behavioural, pharmacological and
      combined interventions were included. Reference lists of included studies were
      hand searched. The outcome measure was self- reported tobacco abstinence at the
      final follow-up, with biochemical verification where available. Assessment of
      evidence for effectiveness was undertaken using Bayes Factors. RESULTS: A total
      of 659 titles and abstracts were identified. Five studies met the inclusion
      criteria. Four of these were randomized controlled trials and one was a non
      randomized comparative trial. Differences between study features precluded
      meaningful aggregation for a meta-analysis. The four randomized trials all
      yielded Bayes Factors <1, suggesting no effect of the intervention compared with
      the control condition. The non-randomized trial, conducted in tuberculosis
      clinics in Sudan, yielded an extremely high Bayes Factor (>1000), supporting the
      hypothesis of effectiveness; however, the study was judged to have a high risk of
      bias. CONCLUSIONS: As yet, there is no convincing direct evidence that clinical
      smoking cessation interventions, which are found to be effective in Western
      populations, are also effective for Arab smokers. There is an urgent need for
      high quality randomized trials evaluating interventions in this population.

PMID- 30205258
TI  - Bridging medical simulation with computer science and engineering: A growing
      field of study.
AB  - BACKGROUND: Medical simulation has become an essential educational tool in the
      curricula of healthcare professionals. A literature review revealed a knowledge
      gap in healthcare simulation education with respect to the technological
      expertise required to operate highly sophisticated simulation equipment. With
      this motivation, a case study was designed to determine if implementing on-site
      technological expertise allows for the facile navigation of high fidelity
      manikins. Next, a research study was conducted to evaluate engineering students
      understanding of simulation, and their interest to attend a program in medical
      simulation. OBJECTIVES: To determine if on-site technological expertise lifts
      barriers associated with manikin use and to assess levels of understanding and
      interest among engineering students following exposure to the technology used in
      healthcare simulation. DESIGN: A prospective, descriptive study with pre-post
      surveys. SETTINGS: The Nursing Skills and Simulation Center at a New England
      University campus. PARTICIPANTS: Engineering students attending 6 different
      engineering programs (Computer Science, Computer Engineering, Mechanical
      Engineering, Biomedical Engineering, Electrical Engineering and Technology
      Management) and having different educational levels (undergraduate and graduate).
      METHODS: Two assessments were applied to engineering students attending a class
      on technology used in healthcare simulation. A pre-test measured the
      understanding and interest of students in the engineering/computer science
      courses before attending a simulation class. A post-test assessment measured
      their improvement in understanding and interest to learn more about simulation
      technologies. RESULTS: Statistical analysis and comparisons of pre-and post-test
      assessments show a 23% gain in understanding of this field following exposure to
      the healthcare simulation class. Furthermore, post test results show greater than
      67% of those surveyed have an interest in attending a program in healthcare
      simulation. CONCLUSIONS: The results indicate the collaboration of nursing and
      engineering has lifted known barriers to simulation education, and reveal
      engineering students have an interest in the field of medical simulation.

PMID- 30205259
TI  - Virtual health education: Scaling practice to transform student learning: Using
      virtual reality learning environments in healthcare education to bridge the
      theory/practice gap and improve patient safety.
AB  - The advancements in and affordability of technologies offer increasing
      opportunities to modernise healthcare education into packages developed to meet
      the expectations and requirements of the digital generation. Purposefully
      designed and tested Virtual Reality Learning Environments (VRLE) can offer
      healthcare students the means to access and revisit learning materials in ways
      that enhance education and meet a range of needs; including those with specific
      learning differences and those who have traditionally been disenfranchised.
      Furthermore, this will make healthcare education much more readily available to
      those who have been previously marginalised by distance. This paper argues that
      Virtual Reality (VR) has the unique potential to transform healthcare education
      and suggests that more providers should consider collaborating with developers
      and investing in the technology.

PMID- 30205260
TI  - Novel tacrine platinum(II) complexes display high anticancer activity via
      inhibition of telomerase activity, dysfunction of mitochondria, and activation of
      the p53 signaling pathway.
AB  - In this work, we designed and synthesized tacrine platinum(II) complexes
      [PtClL(DMSO)]?CH3OH (Pt1), [PtClL(DMP)] (Pt2), [PtClL(DPPTH)] (Pt3), [PtClL(PTH)]
      (Pt4), [PtClL(PIPTH)] (Pt5), [PtClL(PM)] (Pt6) and [PtClL(en)] (Pt7) with 4,4'
      dimethyl-2,2'-bipyridine (DMP), 4,7-diphenyl-1,10-phenanthroline (DPPTH), 1,10
      phenanthroline (PTH), 2-(1-pyrenecarboxaldehyde) imidazo [4,5-f]-[1,10]
      phenanthroline (PIPTH), 2-picolylamine (PM) and 1,2-ethylenediamine (en) as
      telomerase inhibitors and p53 activators. Biological evaluations demonstrated
      that Pt1Pt7 exhibited cytotoxic activity against the tested NCIH460, Hep-G2, SK
      OV-3, SK-OV-3/DDP and MGC80-3 cancer cell lines, with Pt5 displaying the highest
      cytotoxicity. Pt5 exhibited an IC50 value of 0.13 +/- 0.16 MUM against SK-OV
      3/DDP cancer cells and significantly reduced tumor growth in a Hep-G2 xenograft
      mouse model (tumor growth inhibition (TGI) = 40.8%, p < 0.05) at a dose of 15.0
      mg/kg. Interestingly, Pt1Pt7 displayed low cytotoxicity against normal HL-7702
      cells. Mechanistic studies revealed that these compounds caused cell cycle arrest
      at the G2/M and S phases, and regulated the expression of CDK2, cyclin A, p21,
      p53 and p27. Further mechanistic studies showed that Pt5 induced SK-OV3/DDP cell
      apoptosis via dysfunction of mitochondria, inhibition of the telomerase activity
      by directly targeting the c-myc promoter, and activation of the p53 signaling
      pathway. Taken together, Pt5 has the potential to be further developed as a new
      antitumor drug.

PMID- 30205261
TI  - Antibacterial and antioxidant activities for natural and synthetic dual-active
      compounds.
AB  - Antimicrobial resistance is widely recognized as a grave threat to global health
      in the 21st century, since the past decades have seen a dramatic increase in
      human-pathogenic bacteria that are resistant to one or multiple antibiotics. New
      antimicrobial agents are urgently required, particularly in the treatment of
      chronic infections such as cystic fibrosis, often associated with persistent
      colonization by drug-resistant pathogens and epithelial damage by pulmonary
      oxidative stress. In such events, it would be favourable to find agents that
      could have antioxidant and antibacterial activities combined in one molecule. The
      discovery of compounds that can show a dual-target activity considerably
      increased in the last years, reflecting the growing confidence that this new
      approach could lead to better therapeutic solutions for complex multigenic
      diseases. The aim of this review is to report those natural and synthetic
      compounds displaying significant antioxidant and antibacterial activities. In
      recent years there has been a growing attention on plant-derived antimicrobials
      as an alternative to antibiotics, for their efficacy and low tendency in
      developing bacterial resistance. Moreover, it was found that some natural
      products could enhance the activity of common antibiotics displaying a
      synergistic effect. We then report some selected synthetic compounds with an in
      built capacity to act on two targets or with the combination in a single
      structure of two pharmacophores with antioxidant and antibacterial activities.
      Recent literature instances were screened and the most promising examples of dual
      active antibacterial-antioxidant molecules were highlighted.

PMID- 30205262
TI  - Molecular modeling of conformational dynamics and its role in enzyme evolution.
AB  - With increasing computational power, biomolecular simulations have become an
      invaluable tool for understanding enzyme mechanisms and the origins of enzyme
      catalysis. More recently, computational studies have started to focus on
      understanding how enzyme activity itself evolves, both in terms of enhancing the
      native or new activities on existing enzyme scaffolds, or completely de novo on
      previously non-catalytic scaffolds. In this context, both experiment and
      molecular modeling provided strong evidence for an important role of
      conformational dynamics in the evolution of enzyme functions. This contribution
      will present a brief overview of the current state of the art for computationally
      exploring enzyme conformational dynamics in enzyme evolution, and, using several
      showcase studies, illustrate the ways molecular modeling can be used to shed
      light on how enzyme function evolves, at the most fundamental molecular level.

PMID- 30205263
TI  - Investigation on biomass steam gasification in a dual fluidized bed reactor with
      the granular kinetic theory.
AB  - The dual fluidized bed (DFB) reactor is promising to convert biomass into high
      quality syngas efficiently. In this work, a three-dimensional model is built
      based on the granular kinetic theory to predict the biomass steam gasification in
      dual fluidized bed reactors. The model is firstly validated against a series of
      experimental results. Then, the effects of some essential operation parameters
      including the biomass flow rate (Fb), the steam to fuel ratio (Rsf) and the
      gasification temperature (Tg) on the biomass steam gasification properties in a
      DFB reactor are comprehensively analyzed with the orthogonal method. In the
      concerned ranges of the operation parameters, the cold gas efficiency is found to
      be the most sensitive to Fb and least sensitive to Tg. The optimal cold gas
      efficiency of the DFB gasifier is 82.9% when Fb, Rsf and Tg are 15 kg/h, 1.5 and
      900  degrees C, respectively, and the H2 mole fraction is 46.62%.

PMID- 30205265
TI  - Boosting the fermentable sugar yield and concentration of corn stover by
      magnesium oxide pretreatment for ethanol production.
AB  - MgO pretreatment was investigated to boost the fermentable sugars derived from
      corn stover with LHW pretreatment as control. Compared to LHW pretreatment, MgO
      pretreatment caused twice hemicellulose recovery (42 vs 21%). Double
      hemicellulose recovery not only didn't affect glucose yield but increased xylose
      yield by 13% and total sugar yield by 6% under the optimal conditions
      (pretreatment: 10% biomass loading, 0.1 mol/L MgO, 190  degrees C, and 40 min;
      hydrolysis: pretreated biomass loading of 10 g/100 mL, enzyme loading of 1 mL/g
      pretreated biomass, 50  degrees C, and 120 h). A total sugar concentration of 50
      g/L was obtained under the above conditions. Besides, the enzyme component
      hydrolyzing xylan may be prone to deactivation by lignin residues in pretreated
      biomass. Both SEM and FTIR analyses indicate that MgO effectively disrupted the
      biomass structures and enlarged the exposed surface area of carbohydrates, thus
      boosting the enzymatic hydrolysis and fermentable sugars for ethanol production.

PMID- 30205266
TI  - Dendritic solutions to the credit assignment problem.
AB  - Guaranteeing that synaptic plasticity leads to effective learning requires a
      means for assigning credit to each neuron for its contribution to behavior. The
      'credit assignment problem' refers to the fact that credit assignment is non
      trivial in hierarchical networks with multiple stages of processing. One
      difficulty is that if credit signals are integrated with other inputs, then it is
      hard for synaptic plasticity rules to distinguish credit-related activity from
      non-credit-related activity. A potential solution is to use the spatial layout
      and non-linear properties of dendrites to distinguish credit signals from other
      inputs. In cortical pyramidal neurons, evidence hints that top-down feedback
      signals are integrated in the distal apical dendrites and have a distinct impact
      on spike-firing and synaptic plasticity. This suggests that the distal apical
      dendrites of pyramidal neurons help the brain to solve the credit assignment
      problem.

PMID- 30205264
TI  - Malic acid production from biodiesel derived crude glycerol using morphologically
      controlled Aspergillus niger in batch fermentation.
AB  - In the present investigation, the effects of crude glycerol concentration, spore
      inoculum concentration, yeast extract concentration and shaking frequency on seed
      morphology of Aspergillus niger PJR1 on malic acid production were investigated
      and dispersed fungal mycelium with higher biomass (20.25 +/- 0.91 g/L) was
      obtained when A. niger PJR1 grow on crude glycerol. Dry cell weight under
      dispersed fermentation was 21.28% higher than usual pellet fermentation. The
      optimal crude glycerol, nitrogen source and nitrogen source concentration were
      found to be 160 g/L, yeast extract and 1.5 g/L, respectively. Batch fermentation
      in a shake flask culture containing 160 g/L crude glycerol resulted in the yield
      of malic acid 83.23 +/- 1.86 g/L, after 192 h at 25  degrees C. Results revealed
      that morphological control of A. niger is an efficient method for increased malic
      acid production when crude glycerol derived from biodiesel production is used as
      feedstock.

PMID- 30205268
TI  - Using domperidone to induce and sustain hyperprolactinemia in late-pregnant
      gilts.
AB  - Prolactin controls mammary development as well as the lactogenic and
      galactopoietic processes in sows and increasing prolactin during gestation can
      augment milk yield. The dopamine receptor antagonist domperidone can increase
      circulating prolactin concentrations in pigs, but the ideal dose to achieve
      sustained hyperprolactinemia remains unknown. An experiment was performed to
      develop a protocol for using domperidone in studies of rapid and sustained
      hyperprolactinemia in late-pregnant gilts. On day 90 of gestation, gilts were
      divided into 4 groups: (1) intramuscular (IM) injections of canola oil (3 mL,
      controls [CTL], n = 9), (2) IM injections with 0.1 mg/kg BW of domperidone (low
      [LO], n = 8), (3) IM injections with 0.5 mg/kg BW of domperidone (medium [ME], n
      = 11), and (4) IM injections with 1.0 mg/kg BW of domperidone (high [HI], n =
      11). Injections were given daily at 8:05 from days 90 to 109 of gestation.
      Treated gilts also received domperidone per os (0.5 mg/kg BW) at 8:00 and 20:00
      on days 89, 90, and 91 of gestation. Three jugular blood samples were collected
      from all gilts at 6-h intervals on days 89, 90, and 91 of gestation, then twice
      daily on days 92, 93, and 94. Thereafter, samples were obtained at 8:00 every
      other day until day 114 of gestation. Blood was sampled serially from 9 CTL and
      11 HI gilts on days 89 and 94 of gestation. On day 89 of gestation, prolactin
      concentrations for LO, ME, and HI gilts increased within 6 h of domperidone per
      os (P < 0.001). From days 89 until 93 of gestation, the area under the curve
      (AUC) for LO, ME, and HI gilts was greater than that for CTL gilts (P < 0.001),
      whereas from days 89 until 114, ME and HI gilts had greater AUC than CTL and LO
      gilts (P < 0.05). Results demonstrate that the combination of per os treatment
      with IM injections of 0.5 mg/kg of domperidone in an oil emulsion leads to the
      rapid and sustained release of prolactin over 24 d in late-pregnant gilts. Higher
      doses of domperidone failed to further increase circulating prolactin levels.
      These findings provide a useful strategy to induce sustained hyperprolactinemia
      in late-pregnant gilts.

PMID- 30205267
TI  - Inhibition evaluation of ABC powder in aluminum dust explosion.
AB  - To investigate the inhibition effect of ABC powder for 5 MUm and 30 MUm aluminum
      dust explosions, a standard 20 L spherical chamber was employed to determine the
      explosion severity of Al/ABC mixtures and the MIC (minimum inerting
      concentration) of ABC powder. Results showed that the MIC increased as the
      concentration of aluminum dust increased. Meanwhile, the MIC decreased with the
      declining particle diameter of ABC but increased with the reducing diameter of
      the aluminum particles. SEEP (suppressant enhanced explosion parameter)
      phenomenon was observed when the concentration of ABC powder was low. To reveal
      the enhancement mechanism of ABC powder, explosion severity of NH3 and Al/NH3
      mixture was also determined. Results showed that the explosion severity of
      aluminum dust was significantly enhanced by adding NH3. Scanning electron
      microscopy showed that the particles of the explosion residues of Al/NH3 mixture
      and Al/ABC mixture were significantly larger than those of pure aluminum
      explosion residues. X-ray photoelectron spectroscopy revealed that the major
      explosion products of Al/NH3 mixture was Al2O3. Explosion products of Al/ABC
      mixture were mainly comprised of Al2O3 and P2O5. The inhibition mechanism of
      aluminum dust explosion by ABC powder was summarized systematically based on
      these results.

PMID- 30205270
TI  - Inhibition by free nitrous acid (FNA) and the electron competition of nitrite in
      nitrous oxide (N2O) reduction during hydrogenotrophic denitrification.
AB  - Hydrogenotrophic denitrification is a promising technology for nitrate removal
      from organic-deficient wastewater or groundwater, and the attention of nitrous
      oxide (N2O) emission during this process is required. Both nitrite and free
      nitrous acid (FNA or HNO2) were reported to exert significant effects on N2O
      reduction in heterotrophic denitrification, whereas, little knowledge has been
      obtained in hydrogenotrophic denitrification. In this study, we conducted a
      series of batch tests to comprehensively investigate the effects of nitrite, pH
      and FNA on N2O production and reduction in a hydrogenotrophic denitrification
      process. The results showed that N2O reduction rate decreased under both
      conditions of low pH and presence of nitrite, which would exert synergetic
      inhibition on N2O reduction. The potential mechanisms that give rise to the
      results included electron competition and FNA inhibition. Electron competition
      between nitrite and N2O reductases occurred when both nitrite and N2O were added,
      which might contribute to the decrease in the N2O reduction rate. The electron
      supply, which was obtained from the uptake of molecular hydrogen, declined with
      increasing FNA concentration according to a logarithmic model (R2 = 0.9240).
      Additionally, the electron consumption rate of N2O reductase to nitrite reductase
      ratio was initially stable and then decreased with increasing FNA concentration.
      The inhibition of N2O reduction by FNA was determined to be reversible. The study
      suggested that both of the electron supply and N2O reduction in hydrogenotrophic
      denitrification could be inhibited by FNA.

PMID- 30205269
TI  - Characterization of insulin and IGF-1 receptor binding in equine liver and
      lamellar tissue: implications for endocrinopathic laminitis.
AB  - Although it is well established that equine laminitis can be triggered by extreme
      hyperinsulinemia, the mechanism of insulin action is not known. High
      concentrations of insulin lead to separation of the weight-bearing apparatus from
      the hoof wall and are associated with an increased cycle of cell death and
      proliferation in the lamellae. Gene expression and immunohistochemistry studies
      have indicated that the lamellae are sparsely populated with insulin receptors,
      whereas IGF-1 receptors (IGF-1R) are abundant, suggesting that the action of
      insulin may be mediated by insulin binding to the IGF-1R. To investigate this
      possibility, cell membrane fragments containing IGF-1R were extracted from the
      livers of 6 horses and the lamellae of >50 horses euthanized for nonresearch
      purposes at an abattoir. Radioligand-binding studies using 125I-IGF-1 and 125I
      insulin confirmed an abundance of high-affinity IGF-1R in the liver (KD 0.11 nM,
      Bmax 223 fmol/mg protein) and lamellae (KD 0.16 nM, Bmax 243 fmol/mg protein).
      However, the affinity of insulin for binding to the lamellar IGF-1R (Ki 934 nM)
      was >5,800 fold less than that of IGF-1, suggesting that insulin is unlikely to
      bind to equine IGF-1R at physiological concentrations. Although insulin receptors
      could be detected in the liver (KD 0.48 nM, Bmax 123 fmol/mg protein), they were
      barely detectable in lamellae (estimated Bmax 14 fmol/mg protein). There was no
      evidence to support the presence of insulin/IGF-1 hybrid receptors in either
      tissue. These findings suggest that insulin does not act directly through IGF-1
      receptors and that an alternative theory is required to explain the mechanism of
      insulin action in laminitis.

PMID- 30205271
TI  - Cadmium-induced serotonergic neuron and reproduction damages conferred lethality
      in the nematode Caenorhabditis elegans.
AB  - Cadmium is a ubiquitous environmental toxicant. The use of Caenorhabditis elegans
      as a model for monitoring cadmium exposure has revealed several conserved
      signaling pathways. However, little is known about the killing process during
      lethality assay. In the present study, we investigated the effects serotonergic
      neuronal and reproductive damages on cadmium exposure in C. elegans. We found
      that sterile hermaphrodites, males and worms that passed reproduction span
      presented high cadmium resistance compared to those of young adults. The results
      demonstrated that reproduction process other than reproduction capacity conferred
      cadmium sensitivity. Cadmium exposure resulted in high ratio bagging phenotype,
      which was a severe reproductive deficit with embryos hatched internally that
      could cause worms to die early. The mechanism of bagging formation was ascribed
      to cadmium-induced egg laying deficiency that led embryos to retain and hatch in
      uterus. The addition of serotonin and imipramine promoted egg laying and thereby
      increased cadmium resistance. The results demonstrated that vulval muscles
      responsible for egg laying were still functional, while the serotonergic
      hermaphrodite specific neurons might be dysfunctional under cadmium exposure.
      Cadmium exposure resulted in shrinkage of serotonergic neuronal body and reduced
      expressions of tryptophan hydroxylase, the key enzyme for serotonin synthesis.
      The protection of serotonergic neuron through transient thermal preconditioning
      improved survival rate. In conclusion, our study demonstrated that damages of
      serotonergic neurons and reproduction conferred to cadmium-induced lethality.

PMID- 30205272
TI  - Poly(amine) modified kaolinite clay for VOC capture.
AB  - Polyethylenimine (PEI) functionalized kaolinite clay was successfully prepared,
      characterized, and assessed for the remediation of volatile organic compounds
      (VOCs) comprising the aldehyde, carboxylic acid, and disulfide functional group
      classes. A gas chromatographic vapor capture assay evaluated the capability of
      unmodified and modified clay material to capture representative aldehyde,
      carboxylic acid, and disulfide VOCs in a laboratory setting. Unmodified kaolinite
      (Kao) clay was moderately or poorly effective at remediating these VOCs, while
      the poly(amine) functionalized Kao was capable of capturing VOCs in the vapor
      phase with reductions up to 100%. Sample cartridge tubes were packed with PEI
      functionalized clay in order to assess their ability to reduce the detectable
      volatile fatty acid load at an open-air rendering plant in a relevant field test
      for applying these materials in a packed-bed scrubber application. The PEI-Kao
      packed cartridges were capable of significantly reducing the detectable
      concentration of volatile fatty acid effluent from the rendering operation. These
      volatile fatty acids are major contributors to nuisance odors associated with
      rendering.

PMID- 30205273
TI  - Characterizing replication kinetics and plaque production of type I feline
      infectious peritonitis virus in three feline cell lines.
AB  - Investigating type I feline coronaviruses (FCoVs) in tissue culture is critical
      for understanding the basic virology, pathogenesis, and virus-host interactome of
      these important veterinary pathogens. This has been a perennial challenge as type
      I FCoV strains do not easily adapt to cell culture. Here we characterize
      replication kinetics and plaque formation of a model type I strain FIPV Black in
      Fcwf-4 cells established at Cornell University (Fcwf-4 CU). We determined that
      maximum virus titers (>107 pfu/mL) were recoverable from infected Fcwf-4 CU cell
      free supernatant at 20 h post-infection. Type I FIPV Black and both biotypes of
      type II FCoV formed uniform and enumerable plaques on Fcwf-4 CU cells. Therefore,
      these cells were employable in a standardized plaque assay. Finally, we
      determined that the Fcwf-4 CU cells were morphologically distinct from feline
      bone marrow-derived macrophages and were less sensitive to exogenous type I
      interferon than were Fcwf-4 cells purchased from ATCC.

PMID- 30205274
TI  - Validation of ICH score in a large urban population.
AB  - OBJECTIVES: Hemorrhagic stroke cause around 10-20% of all strokes. ICH
      (Intracerebral Hemorrhage) score is a grading scale used to determine survival
      outcome after nontraumatic ICH at 30 days. It is a 6-point scale based on 5
      independent variables, which are graded based on the weight of their association.
      These 5 variables are the Glasgow coma scale (GCS), ICH Volume, Intraventricular
      hemorrhage (IVH), Infratentorial origin and age. The aim of our study is to
      validate the ICH score in our population. MATERIALS AND METHODS: We conducted a
      retrospective chart review of 245 adult patients who presented with acute ICH to
      University Hospital, Newark between 1/1/2012 to 12/30/2015. GCS recorded in
      Emergency Department was used. Initial Computed tomography (CT) Head was used for
      calculating volume, IVH, and location origin, while ICH Volume was calculated
      using the ABC/2 method. The primary outcome was 30-day mortality. Patients with a
      hemorrhagic transformation of ischemic strokes or traumatic ICH were excluded.
      RESULTS: 245 patients met our inclusion criteria. 30-day mortality was 36%. ICH
      scores ranged from 0 to 5, and an increase in the ICH score was associated with
      an increase in 30-day mortality. 4 variables in the ICH score had a significant
      association with 30-day mortality: ICH Volume >=30 ml (OR, 17.24; 95% CI, 8.33
      35.66; P < 0.001), IVH (OR, 6.91; 95% CI, 3.72-12.85; P < 0.001), low GCS (P <
      0.001) and infratentorial origin of bleed significant (OR, 2.17; 95% CI, 1.07
      4.40; P 0.039). However, the association of age >= 80 years with respect to 30
      day mortality wasn't statistically significant in our group (OR, 1.49; 95% CI,
      0.70-3.17; P 0.325). CONCLUSIONS: Our study is one of the largest done at a
      single urban center to validate the ICH score. Age >= 80 years wasn't
      statistically significant with respect to 30-day mortality in our group.
      Restratification of the weight of individual variable in the ICH equation with
      modification of the ICH score can potentially more accurately establish mortality
      risk. Nevertheless, the overall prediction of mortality was accurate and
      reproducible in our study.

PMID- 30205275
TI  - The clinical significance of redundant nerve roots of the cauda equina in lumbar
      spinal stenosis patients: A systematic literature review and meta-analysis.
AB  - OBJECTIVES: Decompression surgery for lumbar spinal stenosis (LSS) is the most
      performed spine surgery procedure in patients older than 65 years. Around 40% of
      LSS patients scheduled for decompression surgery have evidence of redundant nerve
      roots (RNR) of the cauda equina on their magnetic resonance images (MRI). Little
      is known about the clinical significance of RNR in LSS patients. The objective
      was to assess the effects of RNR on clinical scores and recovery in older adults
      diagnosed with LSS. PATIENTS AND METHODS: A systematic literature search was
      performed in April 2018 on PubMed, Web of Science, MEDLINE and Cumulative Index
      to Nursing and Allied Health Literature (CINAHL). Prospective and retrospective
      cohort studies undertaken to assess differences in clinical outcomes in patients
      diagnosed with LSS with versus without evidence of RNR on their MRIs were
      selected. Two authors independently selected studies, abstracted data and
      assessed risk of bias. We calculated weighted mean differences (WMD) for
      continuous variables and odds ratio (OR) for variables reported in frequencies.
      RESULTS: Seven studies comprising a total of 1046 LSS patients were included in
      the meta-analysis. LSS patients with evidence of RNR (RNR+) were older, WMD 5.7
      95% CI [2.2-9.2], p = 0.001, had smaller cross sectional area (CSA) of the
      stenotic level, WMD -12.2 95% CI [-17.7 to -6.7], p < 0.0001 and longer symptom
      onset duration, WMD 13.2 95% CI [-0.2-26.7], p = 0.05. The pooled preoperative
      clinical score in the RNR + group was worse but the difference was not
      statistically significant, WMD -3.8 95% CI [-7.9 to 0.2], p = 0.07. After
      decompression surgery RNR + patients had worse clinical scores, -4.7 95% CI [-7.3
      to -2.1], p = 0.0004 and lower recovery rates, -9.8 95% CI [-14.8 to -4.7], p =
      0.0001. CONCLUSION: There is limited quality evidence that RNR + patients are
      older, have a longer symptom history and present higher degrees of lumbar
      stenosis as given by the narrow CSA in comparison to RNR- patients. After
      decompression surgery RNR + patients have worse clinical scores and lower
      recovery rates. In view of these results RNR can be seen as a negative prognostic
      factor in LSS patients.

PMID- 30205276
TI  - Policy, paperwork and 'postographs': Global indicators and maternity care
      documentation in rural Burkina Faso.
AB  - Targets and indicators set at the global level are powerful tools that govern
      health systems in low-income countries. Skilled birth attendance at a health
      facility is an important indicator for monitoring maternal mortality reduction
      worldwide. This paper examines how health workers negotiate policy implementation
      through the translation of clinical care into registries and reports. It does so
      by analysing the links between the global policy of institutional births and the
      role of documentation in the provision of birth care in primary health centres in
      Burkina Faso. Observations of health workers' practices in four primary maternity
      units (one urban, one semi-urban and two rural) conducted over a 12-week period
      in 2011-2012 are analysed alongside 14 in-depth interviews with midwives and
      other health workers. The findings uncover the magnitude of reporting demands
      that health workers experience and the pressure placed on them to provide the
      'right' results, in line with global policy objectives. The paper describes the
      way in which they document inaccurate accounts, for example by completing the
      labour surveillance tool partograph after birth, thus transforming it into a
      'postograph', to adhere to the expectations of health district officers. We argue
      that the drive for the 'right' numbers might encourage inaccurate reporting
      practices and it can feed into policies that are incapable of addressing the
      realities experienced by frontline health workers and patients. The focus on
      producing indicators of good care can divert attention from actual care, with
      profound implications for accountability at the health centre level.

PMID- 30205277
TI  - Digitized patient-provider interaction: How does it matter? A qualitative meta
      synthesis.
AB  - Sociological interest in the digitization of health has predominantly been
      studied using qualitative approaches. Research in this field has grown steadily
      since the late 1990's but to date, no synthesis has been conducted to integrate
      this now rather comprehensive corpus of data. In this paper we present a meta
      ethnography of 15 papers reporting qualitative studies of digitally mediated
      patient - professional interactions. By dissecting the detailed descriptions of
      digitized practices in this most basic relationship in health care, we explore
      how these studies can illuminate important aspects of social relations in
      contemporary society. Our interpretative synthesis enables us to reassert a
      sociological view that places changes in social structures and interaction at the
      core of questions about the digitization of health care. Our synthesis of this
      literature identifies four key concepts that point at structural processes of
      change. We argue that when patient-professional interactions are digitized,
      relations are respatialized, and there are reconnections of relational
      components. These lead to empirically specific reactions, which can be
      characterized as reconstitutions and renegotiations of social practices which in
      turn are related to the reconfiguration of basic social institutions. We propose
      a new direction for exploring the digitalization of health care to illuminate how
      digital health is related to contemporary social change.

PMID- 30205278
TI  - Mass incarceration, race inequality, and health: Expanding concepts and assessing
      impacts on well-being.
AB  - We explore race differences in how individuals experience mass incarceration, as
      well as in mass incarceration's impacts on measures of well-being that are
      recognized as major social determinants of health. We draw on baseline data from
      a sample of 302 men and women recently released from prison/jail or placed
      directly onto probation in New Haven, Connecticut (CT) for drug related offenses
      and followed at 6-month intervals for two years (2011-2014). We describe race
      differences in experiences of mass incarceration and in its impacts on well
      being; and we conduct mediation analyses to analyze relationships among race,
      mass incarceration, and well-being. Blacks reported fewer adult convictions than
      whites, but an average of 2.5 more adult incarcerations. Blacks were more likely
      to have been incarcerated as a juvenile, spent time in a juvenile facility and in
      an adult facility as a juvenile, been on parole, and experienced multiple forms
      of surveillance. Whites were more likely to report being caught by the police
      doing something illegal but let go. Blacks were more likely to report any impact
      of incarceration on education, and dropping out of school, leaving a job, leaving
      their longest job, and becoming estranged from a family member due to
      incarceration. Whites were more likely to avoid getting needed health or social
      services for fear of arrest. Overall, Blacks reported a larger number of impacts
      of criminal justice involvement on well-being than whites. Number of adult
      incarcerations and of surveillance types, and being incarcerated as a juvenile,
      each mediated the relationship among race, mass incarceration, and well-being.
      Though more research is necessary, experiences of mass incarceration appear to
      vary by race and these differences, in turn, have implications for interventions
      aimed at addressing the impacts of mass incarceration on health and well-being.

PMID- 30205279
TI  - A life in waiting: Refugees' mental health and narratives of social suffering
      after European Union border closures in March 2016.
AB  - RATIONALE: In 2015, an estimated 856,723 refugees, predominantly from Syria,
      Afghanistan, and Iraq arrived in Greece as an entry point into the European
      Union. The border of the Former Yugoslav Republic of Macedonia closed in March
      2016, blocking a popular route for refugees through Europe, and left around
      60,000 people stranded in Greece. OBJECTIVE: A mixed-method study was conducted
      among refugees in the regions of Attica, Epirus, and Samos between November 2016
      and February 2017. The epidemiological survey showed that depending on study
      sites between 73% and 100% of the refugees suffered from anxiety disorder. The
      explanatory qualitative study aimed to understand refugees' mental health and
      narratives of social suffering in regards to experienced violence, the effect of
      current border closures, and the lack of an onward journey. METHOD: The
      explanatory qualitative study included 47 in-depth interviews and five focus
      group discussions with refugees purposely recruited through the concomitant
      epidemiological survey, representing both genders and a range of nationalities
      and ages. Data were thematically analysed to identify emergent patterns and
      categories using NVivo 11. RESULTS: The refugees overwhelmingly reported
      experiencing uncertainty and lack of control over their current life and future,
      which caused psychosocial distress and suffering. The passivity of life in
      refugee camps aggravated feelings of meaninglessness and powerlessness. The
      disruption of key social networks and absence of interactions with the
      surrounding Greek society led to feelings of isolation and being unwelcome.
      CONCLUSIONS: Refugees in Greece experience psychosocial distress and social
      suffering as a consequence of their uncertain and disrupted lives and the loss of
      social networks. Faster and transparent asylum procedures, the development of
      meaningful and empowering activities, and fostered social interactions with the
      surrounding society would contribute to alleviating their psychosocial suffering.

PMID- 30205280
TI  - How to MEK the best of uveal melanoma: A systematic review on the efficacy and
      safety of MEK inhibitors in metastatic or unresectable uveal melanoma.
AB  - BACKGROUND: BRAF and MEK inhibitors have demonstrated significant survival
      benefits for patients with cutaneous melanoma. However, their use for uveal
      melanoma (UM) is less established. The aim of this systematic review was to
      summarise the current evidence on the efficacy and safety of MEK inhibitors in
      metastatic UM. METHODS: We performed a systematic literature search in MEDLINE,
      Embase and the Cochrane Library CENTRAL from 1946 through 17 April 2018.
      Abstracts of oncologic conferences, trial registers and reference lists were
      handsearched for relevant publications. The risk of bias was assessed with the
      Cochrane Risk of Bias Tool. RESULTS: Of 590 records identified, six studies met
      the eligibility criteria and were included in the qualitative synthesis. Data
      were available for selumetinib +/- dacarbazine (n = 3), trametinib +/- AKT
      inhibitor (n = 2) and binimetinib plus sotrastaurin (n = 1) from three open-label
      phase II, two open-label phase I and one placebo-controlled phase III trial. The
      overall response rate was available in five studies and ranged from 0 to 14% with
      an average of 2.5%. The median progression-free survival ranged from 3.1 weeks to
      16 weeks. Data on overall survival and 1-year survival rates were not
      consistently reported. Severe treatment-related adverse events were observed most
      commonly for the combination use of selumetinib plus dacarbazine (62%) and
      binimetinib plus sotrastaurin (75%). CONCLUSION: UM is little responsive to MEK
      inhibition, regardless of the inhibiting agent and combination partner. Our
      results do not support the use of MEK inhibitors in UM. Novel treatment options
      are urgently needed in this patient population.

PMID- 30205281
TI  - Multivariate random parameter Tobit modeling of crashes involving aging drivers,
      passengers, bicyclists, and pedestrians: Spatiotemporal variations.
AB  - The increase in 65 years and older population in the United States compels the
      investigation of the crashes involving all aging (65+) roadway users (drivers,
      passengers, bicyclists, and pedestrians) in order to ensure their safety. As
      such, the objective of this research is to provide a spatiotemporal comparative
      investigation of the crashes involving these aging roadway users in Florida via
      concurrently using the same set of predictors in order to obtain comparable
      findings among them. First, a new metric, namely Crash Rate Difference (CRD)
      approach is developed, which enables one to capture potential spatial and
      temporal (e.g., weekend and weekday) variations in crash rates of aging user
      involved crashes. Second, a multivariate random parameter Tobit model is utilized
      to determine the factors that drive both the crash occurrence probability and the
      crash rate of 65+ roadway users, accounting for the unobserved heterogeneity.
      Findings show that there are statistically significant heterogeneous effects of
      predictors on the crash rates of different roadway users, which evidences the
      unobserved heterogeneity across observations. Results also indicate that the
      presence of facilities such as hospitals, religious facilities, or supermarkets
      is very influential on crash rates of 65+ roadway users, advocating that roadways
      around these facilities should be particularly scrutinized by road safety
      stakeholders. Interestingly, the effect of these facilities on crashes also
      differs significantly between weekdays and weekends. Moreover, the roadway
      segments with high crash rates vary temporally depending on whether it is a
      weekday or a weekend. These findings regarding the spatiotemporal variations
      clearly indicate the need to develop and design better traffic safety measures
      and plans addressing these specific roadway segments, which can be tailored to
      alleviate traffic safety problems for 65+ roadway users.

PMID- 30205282
TI  - Driving under the influence of prescription opioids: Self-reported prevalence and
      association with collision risk in a large Canadian jurisdiction.
AB  - BACKGROUND: Motor vehicle collisions are an important contributor to prescription
      opioid use-related morbidity and mortality. The purpose of the current study was
      to estimate the prevalence of driving under the influence of prescription opioids
      (DUIPO) in Ontario, Canada, and to measure the association between this behaviour
      and the risk of a motor vehicle collision. METHODS: Data were based on telephone
      interviews with 7857 respondents who reported having driven in the past year.
      Data were derived from the 2011-2016 cycles of the CAMH Monitor, an ongoing cross
      sectional representative survey of adults aged 18 years and older. A binary
      logistic regression analysis of collision involvement in the previous 12 months
      was conducted and included demographic characteristics (sex, age, marital status,
      education, income, region), driving exposure, poor mental health, non-medical use
      of prescription opioids, and driving after use of alcohol. RESULTS: The
      prevalence of past-year DUIPO was 3.1%. Controlling for demographic
      characteristics, driving exposure, and other risk factors, self-reported DUIPO
      significantly increased the odds of a collision (AdjOR = 1.97; 95% CI 1.08, 3.60;
      p = 0.026). CONCLUSION: Based on these findings, DUIPO is a notable road safety
      issue. Research focused on better understanding the impact of prescription
      opioids on driver behaviour, reducing the prevalence of DUIPO, and improving drug
      impaired driving policy and interventions should be prioritized in public health
      strategies.

PMID- 30205283
TI  - The effects of personality types on self-reported safety behavior: Focused on
      plant workers in Korea.
AB  - We sought to validate a safety behavior tool used in South Korean nuclear power
      plants, and to investigate the effects of HEXACO personality types on safety
      behaviors. The participants were 242 individuals employed in corporate safety
      management who answered the questionnaires on safety behaviors checklist,
      impulsiveness, affectivity, job burnout, and perfectionism. An exploratory factor
      analysis was conducted on the safety behavior items, and the convergent and
      discriminant validity were confirmed through correlational analyses with the
      existing related variables. To examine the individual effects of personality
      variables on the validated safety behavior questionnaire, we introduced control
      variables into a subsequent hierarchical regression analysis. The analyses
      revealed that the personality variables had significant effects on the subscales
      of the safety behavior scale. The present study is significant in that it
      revealed that personality, a broad construct, can predict human errors and safety
      behaviors, which have had previously been found to associate with only specific
      variables, such as stress, impulsiveness, and perfectionism.

PMID- 30205285
TI  - Safety and operational impacts of setting speed limits below engineering
      recommendations.
AB  - This study quantifies the operational and safety impacts of setting posted speed
      limits below engineering recommendations using field data from rural roads in
      Montana. Vehicle operating speeds and historical crash data were collected at
      multiple sites with posted speed limits set equal to engineering recommendations
      and sites with posted speed limits set lower than engineering recommendations.
      Linear, quantile and logistic regression models were estimated to predict mean
      operating speed, 85th percentile operating speed and speed limit compliance,
      respectively, as a function of various roadway characteristics and level of speed
      enforcement. The Empirical-Bayes before-after approach was also used to develop
      crash modification factors (CMFs) that describe the expected change in total and
      fatal + injury crash frequency when setting posted speed limits lower than
      engineering recommendations. Because safety data were collected over a long time
      period, temporal adjustments were incorporated to account for yearly changes in
      crash reporting, traffic characteristics and other variables. The results
      revealed that speed limit compliance worsened as the difference between the
      engineering recommended and posted speed limits increased. The presence of
      verified heavy police enforcement reduced both mean and 85th-percentile operating
      speeds by approximately 4 mph and increased speed limit compliance. The safety
      analysis found a statistically significant reduction in total, fatal + injury,
      and property damage only (PDO) crash frequency at locations with posted speed
      limits set 5 mph lower than engineering recommendations. Locations with posted
      speed limits set 10 mph lower than engineering recommendations experienced a
      decrease in total and PDO crash frequency, but an increase in fatal + injury
      crash frequency. The safety effects of setting speed limits 15 to 25 mph lower
      than engineering recommendations were less clear, as the results were not
      statistically significant, likely due to the small sample of sites included in
      the evaluation. Overall, the results suggest that setting posted speed limits 5
      mph lower than the engineering recommended practice may result in operating
      speeds that are more consistent with the posted speed limits and overall safety
      benefits.

PMID- 30205284
TI  - From partial and high automation to manual driving: Relationship between non
      driving related tasks, drowsiness and take-over performance.
AB  - BACKGROUND: Until the level of full vehicle automation is reached, users of
      vehicle automation systems will be required to take over manual control of the
      vehicle occasionally and stay fallback-ready to some extent during the drive.
      Both, drowsiness caused by inactivity and the engagement in distracting non
      driving related tasks (NDRTs) such as entertainment or office work have been
      suggested to impair the driver's ability to safely handle these transitions of
      control. Thus, it is an open question whether engagement in NDRTs will impair or
      improve take-over performance. METHOD: In a motion-based driving simulator, 64
      participants completed an automated drive that lasted either one or two hours
      using either a partially or highly automated driving system. In the partially
      automated driving condition, a warning was issued after several seconds when
      drivers took both hands off the steering wheel, while the highly automated
      driving system allowed hands-off driving permanently. Drivers were allowed to
      bring along their smartphones and to use them during the drive. They engaged in a
      wide variety of NDRTs such as reading or using social media. At the end of the
      session, drivers had to react to a sudden lead vehicle braking event. In the
      partial automation condition, there was no take-over request (TOR) to notify the
      drivers of the braking vehicle, while in the highly automated condition, the
      situation happened right after the drivers had deactivated the automation in
      response to a TOR. The lead time of the TOR was set at 8 s. Driver's level of
      drowsiness, workload (visual, mental and motoric) from carrying out the NDRT and
      motivational appeal of the NDRT right before the control transition were video
      coded and used to predict the outcome of the braking event (i.e., reaction and
      system deactivation times, minimal Time-to-collision (TTC) and self-reported
      criticality) with a multiple regression approach. RESULTS: In the partial
      automation condition, reaction times to the braking vehicle and situation
      criticality as measured by the minimum TTC could be well predicted. Main
      predictors for increased reaction time were drowsiness and motivational appeal of
      the NDRT. However, visual and mental demand associated with NDRTs did decrease
      reaction time, suggesting that the NDRT helped the drivers to maintain alertness
      during the partially automated drive. Accordingly, drowsiness and motivational
      appeal of the NDRT increased situation criticality, while cognitive load due to
      the NDRT decreased it. In the highly automated condition, however, it was not
      possible to predict system deactivation time (in reaction to the TOR), brake
      reaction time to the braking vehicle and situation criticality by observed
      drowsiness and NDRT engagement. DISCUSSION: The results suggest a relationship
      between the driver's drowsiness and NDRT engagement in partial automation but not
      in highly automated driving. Several explanations for this finding are discussed.
      It could be possible that the lead time of 8 s might have given the drivers
      enough time to complete the driver state transition process from executing NDRTs
      to manual driving, putting them in a position to be able to cope with the driving
      event, while this was not possible in the partial automation condition.
      Methodological issues that might have led to a non-detection of an effect of
      drowsiness or NDRT engagement in the highly automated driving condition, such as
      the sample size and sensitivity of the observer ratings, are also discussed.

PMID- 30205287
TI  - Quantitative assessment of grammar in amyloid-negative logopenic aphasia.
AB  - Logopenic primary progressive aphasia (lvPPA) typically results from underlying
      Alzheimer's disease, but subjects have been reported that do not show beta
      amyloid (Abeta) deposition. These subjects do not differ on neurological and
      speech-language testing from Abeta-positive lvPPA, but they impressionistically
      show increased grammatical deficits. We performed a quantitative linguistic
      analysis of grammatical characteristics in Abeta-negative lvPPA compared to Abeta
      positive lvPPA and agrammatic PPA, which is characterized by increased
      grammatical difficulties. Abeta-negative lvPPA used fewer function words and
      correct verbs but more syntactic and semantic errors compared to Abeta-positive
      lvPPA. These measures did not differ between Abeta-negative lvPPA and agPPA. Both
      lvPPA cohorts showed a higher mean length of utterance, more complex sentences,
      and fewer nouns than agPPA. Abeta-negative lvPPA subjects appear unique and share
      linguistic features with both agPPA and Abeta-positive lvPPA. Quantitative
      language analysis in lvPPA may be able to distinguish those with and without
      Abeta deposition.

PMID- 30205288
TI  - Phenomenology and diagnostic stability of paediatric bipolar disorder in a
      Spanish sample.
AB  - BACKGROUND: Paediatric bipolar disorder (BD) has gained validity, and substantial
      research in the last 20 years has dissipated the controversy surrounding it.
      However, data on the prevalence, prodromes, phenomenology, and longitudinal
      stability of paediatric BD are still required. METHODS: We reviewed the medical
      records of all patients (n = 72) with DSM-IV BD evaluated over a 15-year period.
      We assessed the most frequently present symptoms prior to and at the time of
      diagnosis, the diagnostic stability of the disorder and its subtypes (I, II and
      NOS). RESULTS: Patients [75% boys, median age (interquartile range, IQR) at
      diagnosis 12.6 (9.6-15.7) years] underwent follow up for a median period of 3.86
      (1.8-5.9) years. There was a median delay from symptom onset to diagnosis of 2.3
      (1.2-4.8) years. At the time of diagnosis, 37.5% had BD-I, 8.3% BD-II, and 54.2%
      BD-NOS. At follow-up, 62.5% had BD-I, 8.3% had BD-II, and 23.6% had BD-NOS,
      whereas 4.2% no longer met the DSM-IV criteria for BD. LIMITATIONS: Our sample
      size limited the BD subtype analyses. Some of information was collected
      retrospectively. CONCLUSION: 95.8% of our sample retained a BD diagnosis after a
      median follow-up period of 3.86 years. BD-I patients maintained their diagnosis
      and subtype of BD. Half of all patients with baseline BD-NOS maintained their BD
      subtype, but most of the other half showed conversion to BP-I at follow up. Only
      4.2% of the sample (all with BD-NOS at baseline) did not meet criteria for BD at
      follow up, and these patients were stable.

PMID- 30205286
TI  - Posttraumatic stress disorder and relationship functioning: A comprehensive
      review and organizational framework.
AB  - Posttraumatic stress disorder (PTSD) is associated with impairments in
      relationship functioning. Beyond the abundance of research that has demonstrated
      this basic link, more recent research has begun to explore possible mediators and
      moderators of this association. The present paper reviews and synthesizes
      existing literature in the context of an overarching organizational framework of
      potential ways in which PTSD impacts relationship functioning. The framework
      organizes findings in terms of specific elements of PTSD and comorbid conditions,
      mediators (factors that are posited to explain or account for the association),
      and moderators (factors that are posited to alter the strength of the
      association). Specific symptoms of PTSD, comorbid symptoms, and many of the
      potential mediators explored have extensive overlap, raising questions of
      possible tautology and redundancy in findings. Some findings suggest that non
      specific symptoms, such as depression or anger, account for more variance in
      relationship impairments than trauma-specific symptoms, such as re-experiencing.
      Moderators, which are characterized as individual, relational, or environmental
      in nature, have been the subject of far less research in comparison to other
      factors. Recommendations for future research and clinical implications of the
      findings reviewed are also presented.

PMID- 30205289
TI  - Control of electron transfer in nitrogenase.
AB  - The bacterial enzyme nitrogenase achieves the reduction of dinitrogen (N2) to
      ammonia (NH3) utilizing electrons, protons, and energy from the hydrolysis of
      ATP. Building on earlier foundational knowledge, recent studies provide molecular
      level details on how the energy of ATP hydrolysis is utilized, the sequencing of
      multiple electron transfer events, and the nature of energy transduction across
      this large protein complex. Here, we review the state of knowledge about energy
      transduction in nitrogenase.

PMID- 30205290
TI  - Selection rules on initial structures in parallel cascade selection molecular
      dynamics affect conformational sampling efficiency.
AB  - Parallel cascade selection molecular dynamics (PaCS-MD) is a conformational
      sampling method for generating transition pathways from a given reactant to a
      product. In PaCS-MD, initial structures relevant to conformational transitions of
      proteins are selected and resampled by short-time MD simulations. As a general
      reaction coordinate, a root-mean-square deviation measured from the product
      (RMSD) is employed to rank the resampled configurations. Quantitatively, n
      initial structures are randomly selected from among the top X % of highly ranked
      configurations and resampled again. In PaCS-MD, the selection of initial
      structures and their conformational resampling are repeated as a cycle to promote
      the essential conformational transitions. Therefore, rules for selecting the
      initial structures might affect the conformational sampling efficiency. In the
      present study, to address the conformational sampling efficiency depending on the
      selection rule, the open-closed transition of di-ubiquitin was reproduced by PaCS
      MD based on the resampling from the top X = 0.1, 1.0, 2.0, 5.0, 10.0, 25.0, 30.0,
      40.0, and 50.0% of highly ranked configurations. Judging from broadness of
      sampled conformational area and required cycles, we conclude that the resampling
      from the top ~2.0% of highly ranked configurations might be the most efficient
      for generating a set of transition pathways in PaCS-MD.

PMID- 30205292
TI  - Packaging analysis of counterfeit medicines.
AB  - The authentication of the packaging represents an important step in the
      investigation of suspected counterfeits of pharmaceutical products. The visual
      comparison with a retained sample is the first step to detect a counterfeited
      packaging. Due to the improvement of technologies like printing, the emergence of
      counterfeits with a better appearance can be observed. Moreover counterfeits are
      nowadays often a combination of fake and genuine parts that have been
      manipulated. Authenticating each part of the product is important in the frame of
      the investigation to understand how the counterfeiters proceed, and which
      prevention measures should be taken. Lab instruments like spectrometers can help
      confirm counterfeits of packaging for packaging components on which visually, no
      difference with a reference would be observed. In this study several analytical
      tools were evaluated to help support the authentication of the primary and
      secondary packaging of one medicinal product as an example using seven reference
      materials and five counterfeits. In some cases, visual examination of the
      packaging already enabled to detect counterfeits of the studied features. Also
      the boxes, leaflets and vials have been analysed with Infrared (IR) spectroscopy,
      Raman microspectroscopy, X-ray fluorescence (XRF) spectroscopy, Scanning Electron
      Microscopy (SEM) and microcomputed tomography (microCT). According to the
      obtained results, IR and XRF could support the visual examination of the
      different packaging components. Despite the small amount of counterfeits,
      relevant links could also be detected between the studied cases based on the
      packaging characteristics.

PMID- 30205294
TI  - Revisiting "Genetic Diversity of Symbiotic Dinoflagellates in the Genus
      Symbiodinium".

PMID- 30205293
TI  - Calmodulin-binding proteins: A journey of 40 years.
AB  - The proteins which bind to calmodulin in a Ca2+-dependent and reversible manner
      are known as calmodulin-binding proteins. These proteins are involved in a
      multitude of processes in which Ca2+ and calmodulin play crucial roles. Our group
      elucidated the mechanism and importance of these proteins in normal and diseased
      conditions. Various calmodulin-binding proteins were discovered and purified from
      bovine tissue including a heat stable calmodulin-binding protein 70, calmodulin
      dependent protein kinase VI and a high molecular weight calmodulin-binding
      protein (HMWCaMBP). We observed a complex interplay occurs between these and
      other Ca2+ and calmodulin-binding proteins during cardiac ischemia and
      reperfusion. Purified cardiac HMWCaMBP is a homolog form of calpastatin and an
      inhibitor of the Ca2+-activated cysteine proteases, calpains and therefore can
      have cardioprotective role in ischemic conditions. Calcineurin is a Ca2+ and
      calmodulin-dependent serine/threonine protein phosphatase showed increased
      phosphatase activity in ischemic heart through its direct interaction with Hsp70
      and expression of calcineurin following ischemia suggests self-repair and
      favorable survival outcomes. Calcineurin was also found to be present in other
      tissues including the eye; where its expression and calcineurin phosphatase
      activity varied. In neurons, calcineurin may play a key role in initiating
      apoptosis-related pathways especially in epilepsy. In colorectal cancer we
      demonstrated high calcineurin phosphatase activity and simultaneous
      overexpression of calcineurin. The impact of calcineurin signaling on neuronal
      apoptosis in epilepsy and its use as a diagnostic marker for colorectal cancer
      requires in-depth study.

PMID- 30205291
TI  - Understanding the role of glucose regulated protein 170 (GRP170) as a nucleotide
      exchange factor through molecular simulations.
AB  - Glucose Regulated Protein 170 (GRP170), also called Oxygen Regulated Protein 150
      (ORP150), is a major molecular chaperone resident in the endoplasmic reticulum
      (ER). It belongs to the heat shock protein (HSP70) super family and can be
      induced by conditions such as hypoxia, ischemia and interferences in calcium
      homeostasis. It was recently reported that GRP170 may act as a nucleotide
      exchange factor (NEF) for GRP78 or binding immunoglobulin protein (BiP), and the
      ER canonical HSP70. However, little is known about the mechanism underlying its
      NEF activity. In this study, two homology models of GRP170 were constructed based
      on the X-ray crystal structures of ADP and ATP bound HSP110, a cytosolic homolog
      of GRP170, in order to characterize the differences in the binding modes of both
      ligands. It was observed that the differences in the binding modes of ADP and ATP
      led to a conformation change in the substrate binding domain which could
      potentially influence the binding of its substrates such as BiP. Our findings
      help understand the effect of nucleotide binding on the function of this
      chaperone protein as a NEF as well as the structural differences between GRP170
      and its family members.

PMID- 30205295
TI  - The efficacy of inhaled nitric oxide treatment in premature infants with acute
      pulmonary hypertension.
AB  - BACKGROUND: Although inhaled nitric oxide (iNO) therapy in term infants with
      pulmonary hypertension (PHT) has demonstrated definite benefit, the use of iNO in
      preterm infants remains inconclusive. AIMS: To evaluate the impact of iNO
      treatment in premature infants with acute PHT. STUDY DESIGN: Retrospective
      cohort. SUBJECTS: Infants < 34 weeks' gestational age, admitted during 2010-2016
      to two neonatal units, having treated with iNO for confirmed PHT. A positive
      response was defined by FiO2 reduction >=20% within 3-h post iNO initiation.
      Early PHT was defined when developed within the first 72 h of age. OUTCOME
      MEASURES: The primary outcome was the evaluation of the acute response to iNO
      administration. Secondary outcomes included the comparison of neonatal
      characteristics and outcomes between positive and negative responders, and early
      or late PHT infants. RESULTS: Of the 55 infants of our cohort, 39 (71%) had a
      positive response to iNO administration. No differences noted regarding
      bronchopulmonary dysplasia, intraventricular haemorrhage or other morbidities;
      however, positive responders had significantly higher survival rate in overall
      (77 vs 21%, p = 0.001) and within early PHT subgroup (74 vs 33%, p = 0.044).
      Regression analysis revealed that oligohydramnios (OR 2.834, 95%CI 1.652-6.070)
      and early PHT (OR 1.953, 95%CI 1.377-2.930) were significantly related with a
      positive response. CONCLUSIONS: Preterm infants with confirmed acute PHT respond
      in significant proportion to the iNO administration, especially in the background
      of oligohydramnios or the development of early PHT.

PMID- 30205296
TI  - Maternal behaviors in toddlerhood as predictors of children's private speech in
      preschool.
AB  - Private speech is an important strategy reflecting children's self-regulation,
      and thus understanding how parenting may support private speech can inform
      intervention work on improving self-regulation. The current study longitudinally
      investigated how sensitive parenting and directive parenting in toddlerhood
      interacted to predict preschoolers' private speech in an emotion-eliciting task.
      In toddlerhood, maternal parenting behaviors were observed during two freeplay
      sessions. Preschoolers' social and private speech were transcribed and coded
      during a frustration task. Whereas parenting did not relate to other forms of
      private speech, preschoolers' facilitative task-relevant private speech was
      predicted by the interaction of mothers' sensitive and directive behaviors. When
      sensitivity was high, parents who were less directive had children who used more
      facilitative task-relevant private speech. These findings highlight that
      children's regulation may be supported through the combination of high
      sensitivity and low directiveness when parents and children are engaged in
      unstructured play together.

PMID- 30205297
TI  - Let's do it together! The role of interaction in false belief understanding.
AB  - From the interaction theory perspective, we aimed to verify whether the
      interactive context in which theory of mind is measured can allow children
      younger than 4 years to pass the verbal false belief task (FBT). Therefore, an
      interactive FBT (iFBT) was devised, in which children were actively engaged in
      the story, and was used to test 210 children twice: first when they were 3 years
      old and again when they were 3.5 years old. Most 3-year-olds were unable to pass
      the iFBT (28% passed), but a half year later their performance was enhanced and
      they passed at a rate above chance level (59% passed). In addition, among 3.5
      year-olds, passing the iFBT increases the chance of passing the standard FBT by
      four times. We conclude that the interactive mode of the FBT facilitates false
      belief understanding in children under 4 years of age.

PMID- 30205298
TI  - Patterning counts: Individual differences in children's calculation are uniquely
      predicted by sequence patterning.
AB  - Many studies have examined the cognitive determinants of children's calculation,
      yet the specific contribution of children's patterning abilities to calculation
      remains relatively unexplored. This study investigated whether children's ability
      to complete sequence patterns (i.e., add the missing element into 2-4-?-8)
      uniquely predicted individual differences in calculation and whether these
      associations differed depending on the type of stimuli in these sequence patterns
      (i.e., number, letter, time, or rotation). Participants were 65 children in first
      and second grade (Mage = 7.40 years, SD = 0.44). All children completed four
      tasks of sequence patterning: number, letter, time, and rotation. Calculation was
      measured via addition and subtraction tasks. We also measured cognitive
      determinants of individual differences in calculation-namely symbolic number
      comparison, motor processing speed, visuospatial working memory, and nonverbal IQ
      to verify whether patterning predicted calculation when controlling for these
      additional measures. We observed significant relationships between the patterning
      dimensions and calculation, except for the rotation dimension. Follow-up
      regressions, controlling for the aforementioned cognitive determinants of
      calculation, revealed that the number and time dimensions were strong predictors
      of calculation, whereas the evidence for the letter dimension was only anecdotal
      and the evidence for the rotation dimension was nonexistent, suggesting some
      degree of specificity of different types of sequence patterning in predicting
      calculation. Symbolic magnitude processing remained a powerful unique correlate
      of calculation performance. These findings add to our understanding of individual
      differences in calculation ability, such that sequence patterning could begin to
      be considered as one of the cognitive skills underlying calculation ability in
      young children.

PMID- 30205299
TI  - Causal learning from joint action: Collaboration helps first graders but hinders
      kindergartners.
AB  - This study investigated whether early school-aged children's causal learning from
      collaborative joint action differs from their learning from their own individual
      action or observation. Children in a joint condition performed causal
      interventions with an adult on two causal systems. Children in an independent
      condition took turns and observed an adult perform the same interventions on one
      system and performed the same interventions themselves on the other system. Joint
      action improved first graders' (n = 60) causal inference compared with individual
      action and observation. However, joint action impaired kindergartners' (n = 60)
      inference relative to individual action and observation. These findings
      demonstrate that joint action, as a component of collaborative activity, can help
      or hinder inductive causal learning depending on features of the learner.
      Children's abilities to learn from collaborative joint action undergo a
      developmental shift during the early school years.

PMID- 30205301
TI  - Recent advances in designing nanomaterial based biointerfaces for electrochemical
      biosensing cardiovascular biomarkers.
AB  - Early diagnosis of cardiovascular disease (CVD) is critically important for
      successful treatment and recovery of patients. At present, detection of CVD at
      early stages of its progression becomes a major issue for world health. The
      nanoscale electrochemical biosensors exhibit diverse outstanding properties,
      rendering them extremely suitable for the determination of CVD biomarkers at very
      low concentrations in biological fluids. The unique advantages offered by
      electrochemical biosensors in terms of sensitivity and stability imparted by
      nanostructuring the electrode surface together with high affinity and selectivity
      of bioreceptors have led to the development of new electrochemical biosensing
      strategies that have introduced as interesting alternatives to conventional
      methodologies for clinical diagnostics of CVD. This review provides an updated
      overview of selected examples during the period 2005-2018 involving
      electrochemical biosensing approaches and signal amplification strategies based
      on nanomaterials, which have been applied for determination of CVD biomarkers.
      The studied CVD biomarkers include AXL receptor tyrosine kinase, apolipoproteins,
      cholesterol, C-reactive protein (CRP), D-dimer, fibrinogen (Fib), glucose,
      insulin, interleukins, lipoproteins, myoglobin, N-terminal pro-B-type natriuretic
      peptide (BNP), tumor necrosis factor alpha (TNF-alpha) and troponins (Tns) on
      electrochemical transduction format. Identification of new specific CVD
      biomarkers, multiplex bioassay for the simultaneous determination of biomarkers,
      emergence of microfluidic biosensors, real-time analysis of biomarkers and point
      of care validation with high sensitivity and selectivity are the major challenges
      for future research.

PMID- 30205300
TI  - Recent advancements, challenges, and practical considerations in the mass
      spectrometry-based analytics of protein biotherapeutics: A viewpoint from the
      biosimilar industry.
AB  - The extensive analytical characterization of protein biotherapeutics, especially
      of biosimilars, is a critical part of the product development and registration.
      High-resolution mass spectrometry became the primary analytical tool used for the
      structural characterization of biotherapeutics. Its high instrumental sensitivity
      and methodological versatility made it possible to use this technique to
      characterize both the primary and higher-order structure of these proteins.
      However, even by using high-end instrumentation, analysts face several challenges
      with regard to how to cope with industrial and regulatory requirements, that is,
      how to obtain accurate and reliable analytical data in a time- and cost-efficient
      way. New sample preparation approaches, measurement techniques and data
      evaluation strategies are available to meet those requirements. The practical
      considerations of these methods are discussed in the present review article
      focusing on hot topics, such as reliable and efficient sequencing strategies,
      minimization of artefact formation during sample preparation, quantitative
      peptide mapping, the potential of multi-attribute methodology, the increasing
      role of mass spectrometry in higher-order structure characterization and the
      challenges of MS-based identification of host cell proteins. On the basis of the
      opportunities in new instrumental techniques, methodological advancements and
      software-driven data evaluation approaches, for the future one can envision an
      even wider application area for mass spectrometry in the biopharmaceutical
      industry.

PMID- 30205302
TI  - Untargeted search and identification of metabolites of antiviral agent camphecene
      in rat urine by liquid chromatography and mass spectrometry and studying their
      distribution in organs following peroral administration of the compound.
AB  - Major metabolites of camphecene, a new effective antiviral agent, formed after
      its oral administration to rats and excreted in the urine, were found and
      identified using liquid chromatography coupled to mass spectrometry as well as
      multivariate analysis of HPLC-MS data. The metabolites were found to be
      camphecene glucuronide, camphecene sulfate and the corresponding iminoacid. A
      study of the dynamics of accumulation of camphecene and its metabolites in the
      liver, kidneys, lungs and brain of animals was performed. Maximum concentration
      of camphecene in blood and organs was reached after 1.5-2 h of its
      administration, and the maximal content of the agent in the organs investigated
      was observed in the kidneys. The content of the substance in the lungs was
      comparable to that in the liver. Also, camphecene was found in brain in high
      concentration, thus allowing assumption of its ability to penetrate the blood
      brain barrier and to exert its antiviral properties in the organ. Camphecene
      glucuronide and iminoacid had concentration-time profiles similar to that of
      their precursor, their content being maximal in kidney and liver and 2-3 orders
      of magnitude higher than in lungs and brain. The content of camphecene sulfate
      was of similar level in all organs studied. The results obtained made it possible
      to develop recommendations for therapy with the use of camphecene.

PMID- 30205304
TI  - Development of a novel HPLC method for the determination of the impurities in
      desonide cream and characterization of its impurities by 2D LC-IT-TOF MS.
AB  - A novel HPLC method for the determination of the impurities in desonide cream was
      established and validated for the further improvement of the official monograph
      in USP. Desonide was well resolved from the photodegradation impurity, which
      overlapped with desonide in USP method. The method was validated in accordance to
      the regulatory guidelines recommended by the International Conference on
      Harmonisation and this validation included specificity, limit of detection, limit
      of quantification, linearity and accuracy. Four degradation impurities in
      desonide cream were characterized by a trap-free two-dimensional liquid
      chromatography coupled to high resolution ion trap/time-of-flight mass
      spectrometry (2D LC-IT-TOF MS) in positive mode of electrospray ionization.
      Through the multiple heart-cutting 2D LC approach and online demineralization
      technique, the problem of incompatibility between non-volatile salt mobile phase
      and mass spectrometry was solved completely, and the TIC chromatogram of LC-MS
      could be in conformity with the LC chromatogram of the official analytical method
      in the peak sequence of impurities. In the first dimension, the column was
      Phenomenex Kinetex C8 (4.6 mm * 150 mm, 2.6 MUm) with a non-volatile salt mobile
      phase. In the second dimension, the column was Shimadzu Shim-pack GISS C18 (50 mm
      * 2.1 mm, 1.9 MUm) with a volatile salt mobile phase. The structures of four
      degradation impurities in desonide cream were deduced based on the HPLC-MSn data.
      The established method in this study was simple and reliable for routine quality
      control of desonide cream.

PMID- 30205303
TI  - DNA logic circuits based amplification system for quencher-free and highly
      sensitive detection of DNA and adenosine triphosphate.
AB  - We fabricated a quencher-free and enzyme-free fluorescence detection system by
      employing the DNA logic circuits as signal amplifier and 2-aminopurine as signal
      indicator, and applied it to detect DNA and adenosine triphosphate (ATP). The
      assay system consisted of three hairpin probes with a sequestered 2-aminopurine
      molecule in each stem domain which was defined as inputs A, B and C of the logic
      operation. These three hairpin inputs kept stability and coexisted in reaction
      solution without target. However, adding target to the system would break the
      stability and initiate a dynamic assembly of the three inputs through toehold
      mediated displacement, resulting in the formation of three way junction and the
      liberation of 2-aminopurine from duplex structure. The structural circumstance
      changes from duplex to single stand switched the signal from "off" to "on" due to
      the disarming of base stack interaction, thus attaining amplified fluorescence
      detection without any extra quencher and avoiding the limitation of distance
      independent signal conversion in conventional methods. A limit of detection of
      0.46 pM was achieved for target DNA with high discrimination capability.
      Moreover, the sensing system was expandable for ATP detection. Importantly, the
      method was simple and easy-to-operate. These features make the DNA logic circuits
      adaptable as an enzyme-free and quencher-free amplifier, and thus the proposed
      method offers a powerful platform for DNA and ATP determination, and even other
      biotargets in clinical diagnosis.

PMID- 30205305
TI  - Oral vaccine based on a surface immunogenic protein mixed with alum promotes a
      decrease in Streptococcus agalactiae vaginal colonization in a mouse model.
AB  - The Surface Immunogenic Protein (SIP) of Group B Streptococcus (GBS) had been
      described as a good target for vaccine development. To date, SIP has been
      reported as a highly conserved protein, and in a mouse model it induces
      protection against lethal GBS challenge. Also, similar effects have been
      described by intranasal immunization with a SIP-based vaccine. In this study, we
      show the immune response induced by an oral SIP-based vaccine formulated on alum
      in a mouse model. Our vaccine can reduce vaginal GBS colonization and induce
      specific SIP-antibodies with opsonophagocytosis activities against GBS. Moreover,
      we observed the activation of T-cells producing IFN-gamma, TNF-alpha, IL-10, IL
      2, and increased expression of the transcription factor T-bet, suggesting a Th1
      type humoral response. The oral SIP-based vaccine is a novel alternative in the
      development of a vaccine against GBS.

PMID- 30205306
TI  - Risk of polysubstance use among sexual minority and heterosexual youth.
AB  - BACKGROUND: Relative to heterosexual youth, sexual minority youth exhibit
      increased substance use. Risk for polysubstance use, which magnifies drug-related
      harms, remains largely unexamined for sexual minority youth. This investigation
      used a nationally-representative dataset to compare polysubstance use patterns
      between sexual minority and heterosexual youth. METHODS: The cross-sectional 2015
      CDC's Youth Risk Behavior Surveillance System (N = 15,624) was utilized. Latent
      mixture modeling empirically identified subgroups of youth based on self-reported
      past-month use of alcohol, cigarettes, chewing tobacco/snus/snuff,
      cigars/cigarillos/little cigars, e-cigarettes, marijuana, and past-month binge
      drinking (all dichotomized: 0 = none; 1 = at least once). Adjusting for
      race/ethnicity, sex, and age, the risk for being in each substance-using class,
      was compared between youth who self-identified as heterosexual and gay/lesbian,
      bisexual, or "not sure." RESULTS: Five classes were supported: "non-users"
      (68.19%), "alcohol users" (13.08%; elevated alcohol use and binge drinking
      probabilities), "nicotine/marijuana co-users" (5.80%; elevated nicotine and
      marijuana use), "poly-substance/e-cigarette users" (5.35%; elevated on all
      substances except tobacco-containing products), and "polysubstance/tobacco users"
      (7.59%; elevated for all substances). Relative to heterosexual youth, gay/lesbian
      identified youth were at risk of being "nicotine and marijuana co-users",
      bisexual youth were at risk of being in all four substance-using classes, and the
      "not sure" youth were at risk of being "polysubstance/tobacco users." Select
      disparities were larger for youth who were also female or a minority
      race/ethnicity. CONCLUSIONS: Sexual minority youth, particularly bisexual youth,
      were at increased risk relative to heterosexual youth for polysubstance use.
      Polysubstance use warrants attention in substance use interventions, including
      interventions tailored for sexual minority youth.

PMID- 30205307
TI  - Impact of psychiatric medication co-exposure on Neonatal Abstinence Syndrome
      severity.
AB  - BACKGROUND: Among opioid-exposed infants, psychiatric medication co-exposure is
      common. Our objective was to compare Neonatal Abstinence Syndrome (NAS) outcomes
      based on individual psychiatric medication co-exposures. METHODS: A retrospective
      study of 744 opioid-exposed mother-infant dyads from a single institution was
      performed. Mothers on pharmacotherapy with methadone or buprenorphine at delivery
      were included. Data were collected on maternal demographics, psychiatric
      medication use, and NAS outcomes, including any medication treatment, adjunctive
      medication treatment, length of hospital stay (LOS), and opioid treatment days.
      The extent to which individual psychiatric medication and polypharmacy exposure
      were associated with NAS outcomes was assessed using multivariable regression.
      RESULTS: Fifty-four percent of the mothers were on >=1 psychiatric medication,
      with 32% on >=2 or psychiatric medications (polypharmacy group). In adjusted
      models, polypharmacy exposure was associated with longer LOS (beta = 4.31 days,
      95% CI 2.55-6.06) and opioid treatment days (beta = 3.98 days, 95% CI 2.24-5.72)
      and more treatment with adjunctive medication for NAS (aOR = 2.49, 95% CI 1.57
      3.95). Benzodiazepines were associated with longer LOS (beta = 4.94, 95% CI 2.86
      7.03) and opioid treatment days (beta = 4.86, 95% CI 2.61-6.75), and more
      adjunctive medication treatment (aOR = 2.57, 95% CI 1.49-4.42). Gabapentin was
      associated with longer LOS (beta = 2.79, 95% CI 0.54-5.03), more NAS medication
      treatment (aOR = 2.96, 95% CI 1.18-7.42) including more adjunctive medications
      (aOR = 1.92, 95% CI 1.05-3.53). CONCLUSION: For infants of mothers with OUD who
      are also on concurrent psychiatric medications, polypharmacy was associated with
      worse NAS severity. When medically indicated, limiting use of multiple
      psychiatric medications, particularly benzodiazepines and gabapentin, during
      pregnancy should be considered to improve NAS outcomes.

PMID- 30205309
TI  - Sensitivity of food spoilage fungi to a smoke generator sanitizer.
AB  - Smoke generator sanitizers are easy to handle and can access to hard-to-reach
      places. They are a promising alternative for controlling food and air borne
      fungi, which are known to cause losses in the bakery, meat, and dairy industries.
      Therefore, the present study aimed to evaluate the efficiency of a smoke
      generator sanitizer based on orthophenylphenol against ten fungal species
      relevant to food spoilage. The tests were carried out according to the norms by
      the French protocol NF-T-72281, with adaptations specific for disinfectants
      diffused in the air. The tests were performed in an enclosed room of
      approximately 32 m3. Aspergillus brasiliensis (ATCC 16404), Candida albicans
      (ATCC 10231), Aspergillus flavus (ATCC 9643), Aspergillus chevalieri (IMI
      211382), Cladosporium cladosporioides (IMI 158517), Lichtheima corymbifera (CCT
      4485), Mucor hiemalis (CCT 4561), Penicillium commune (CCT 7683), Penicillium
      polonicum (NGT 33/12), and Penicillium roqueforti (IMI 217568) were exposed to
      the smoke generator sanitizer for 7 h. The product was efficient against C.
      albicans and C. cladosporioides, although it was unable to reduce 4 log of the
      other tested species. The variable sensitivity of the fungal species to the
      sanitizer emphasizes the importance of confronting a target microorganism
      (causing problems in a specific food industry) with the sanitizer aiming to
      control it and obtain satisfactory results in hygiene programs.

PMID- 30205308
TI  - A novel bifunctional fluorescent and colorimetric probe for detection of mercury
      and fluoride ions.
AB  - A fluorescent and colorimetric probe L1 based on a simple coumarin derivative for
      detection of Hg2+ and F- ions was developed. Upon addition of Hg2+ and F- ions,
      L1 underwent desulfurization and desilylation, respectively, to induce marked
      increase in the fluorescence intensity and sharp color change from light yellow
      to dark purple and light brown, respectively. Probe L1 could be used for sensing
      and for quantitative measurement of Hg2+ and F- ions by both UV-vis and
      fluorescence spectra. The bifunctional probe exhibited a high selectivity over
      other competitive cations and anions and could be used in both organic and
      aqueous media over a wide pH range.

PMID- 30205310
TI  - The interaction between sense of mastery, social support, and parental distress
      among mothers with and without serious mental illness.
AB  - BACKGROUND: Social support and sense of mastery are considered important
      resources in coping both with serious mental illness (SMI) and with motherhood
      related challenges. However, their interactive effects on the parental stress of
      mothers with SMI are not clear. METHODS: Scales assessing parental distress,
      social support, and sense of mastery were administered to 60 mothers with SMI and
      60 mothers without SMI. RESULTS: A main effect of sense of mastery and a lack of
      main effect of social support were found in both groups. An interaction effect of
      social support with mastery was found among mothers with SMI revealing that for
      mothers who had a high sense of mastery, social support was beneficial, whereas
      for mothers who had a low sense of mastery, social support was harmful.
      CONCLUSIONS: In practice, attention should be given to the sensitive provision of
      support, balancing between what is needed and what is requested, with the aim of
      not harming an individual's sense of mastery.

PMID- 30205311
TI  - Cancer incidence and all-cause mortality among civilian men and women employed by
      the Royal Norwegian Navy between 1950 and 2005.
AB  - OBJECTIVE: We aimed to investigate cancer incidence and all-cause mortality in a
      cohort of 8358 civilians (5134 men and 3224 women) employed by the Royal
      Norwegian Navy at any time between 1950 and 2005. METHODS: The cohort was
      followed for cancer incidence and all-cause mortality from 1960 through 2015.
      Standardised incidence ratios (SIR) and mortality ratios (SMR) were calculated
      from national rates. Separate SIRs were calculated for a subgroup of male
      workshop workers and another of female cleaners. RESULTS: Overall cancer
      incidence among men was similar to the reference rate; male breast cancer was
      more frequent (SIR = 3.23). Male workshop workers showed a SIR of 1.77 for
      stomach cancer, while their incidence of lympho-haematopoietic cancers was half
      that of the reference rates. Women had increased risks of overall cancer (SIR =
      1.11), lung cancer (SIR = 1.35), and ovarian cancer (SIR = 1.39). Female cleaners
      showed a SIR of 2.33 for bladder cancer and a lowered incidence of brain cancer
      (SIR = 0.18). In the overall cohort, all-cause mortality was lower than expected
      for men (SMR = 0.92) and closer to the reference rate for women (SMR = 0.95).
      CONCLUSION: In men, we observed a lowered all-cause mortality and an excess of
      stomach cancer in workshop workers. In women, increased risks of overall cancer,
      lung cancer and ovarian cancer was seen. An increased risk of bladder cancer and
      a lowered incidence of brain cancer was observed among female cleaners.

PMID- 30205312
TI  - Expansion of the genetic code via expansion of the genetic alphabet.
AB  - Current methods to expand the genetic code enable site-specific incorporation of
      non-canonical amino acids (ncAAs) into proteins in eukaryotic and prokaryotic
      cells. However, current methods are limited by the number of codons possible,
      their orthogonality, and possibly their effects on protein synthesis and folding.
      An alternative approach relies on unnatural base pairs to create a virtually
      unlimited number of genuinely new codons that are efficiently translated and
      highly orthogonal because they direct ncAA incorporation using forces other than
      the complementary hydrogen bonds employed by their natural counterparts. This
      review outlines progress and achievements made towards developing a functional
      unnatural base pair and its use to generate semi-synthetic organisms with an
      expanded genetic alphabet that serves as the basis of an expanded genetic code.

PMID- 30205313
TI  - A flexible 12-channel transceiver array of transmission line resonators for 7 T
      MRI.
AB  - A flexible transceiver array based on transmission line resonators (TLRs)
      combining the advantages of coil arrays with the possibility of form-fitting
      targeting cardiac MRI at 7 T is presented. The design contains 12 elements which
      are fabricated on a flexible substrate with rigid PCBs attached on the center of
      each element to place the interface components, i.e. transmit/receive (T/R)
      switch, power splitter, pre-amplifier and capacitive tuning/matching circuitry.
      The mutual coupling between elements is cancelled using a decoupling ring-based
      technique. The performance of the developed array is evaluated by 3D
      electromagnetic simulations, bench tests, and MR measurements using phantoms.
      Efficient inter-element decoupling is demonstrated in flat configuration on a box
      shaped phantom (Sij < -19 dB), and bent on a human torso phantom (Sij < -16 dB).
      Acceleration factors up to 3 can be employed in bent configuration with
      reasonable g-factors (<1.7) in an ROI at the position of the heart. The array
      enables geometrical conformity to bodies within a large range of size and shape
      and is compatible with parallel imaging and parallel transmission techniques.

PMID- 30205314
TI  - Fibered platinum coil: A novel option for the patients of hydrosalpinx with
      laparoscopic contradiction.
AB  - OBJECTIVE: To investigate the feasibility of proximal tubal occlusion with
      fibered platinum coils in subfertile women with hydrosalpinx, and to observe the
      clinical outcomes of subsequent treatment with in vitro fertilization and embryo
      transfer (IVF-ET). STUDY DESIGN: A prospective study was carried out in a
      university-affiliated teaching hospital. 56 women with uni- or bilateral
      hydrosalpinx received fibered platinum coil placement before IVF-ET. The clinical
      pregnancy rate and live birth rate was evaluated. Data analysis was performed
      with SPSS version 22.0 (SPSS, Inc., Chicago, IL, USA), using two-sided test, and
      a p value < 0.05 was considered statistically significant. The study has been
      registered in the ClinicalTrials. gov with the number of NCT03395301. RESULT(S):
      Successful placement was achieved in 106 fallopian tubes of 55 patients. The
      fibered platinum coils induced complete proximal occlusion in 52 out of 55
      patients in the following 3-month HSG examination. In the 52 patients, 44
      patients received following IVF-ET. The clinical pregnancy rate reached
      60.5%(23/38)and live birth rate reached 60.87% (14/23) in patients less than 40
      years old. CONCLUSION(S): Fibered platinum coil is a new, safe and valuable
      device for hysteroscopic tubal proximal occlusion in subfertile women with
      hydrosalpinx but with laparoscopic contradictions to improve the reproductive
      outcomes of IVF-ET. Capsule: Fibered platinum coil is a new, safe and valuable
      device for hysteroscopic tubal proximal occlusion in subfertile women with
      hydrosalpinx to improve the reproductive outcomes of in vitro fertilization and
      embryo transfer.

PMID- 30205315
TI  - Effect of chlorella supplementation on systematic symptoms and serum levels of
      prostaglandins, inflammatory and oxidative markers in women with primary
      dysmenorrhea.
AB  - OBJECTIVE: Primary dysmenorrhea is one of the most commonly reported disorders
      for women that have unfavorable effects on patient's quality of life. Based on
      the evidences that suggest the anti-inflammatory and analgesic properties of
      chlorella, this double-blind, randomized, placebo controlled clinical trial aimed
      to evaluate the effects of Chlorella supplementation on the severity of menstrual
      pain in a group of young women with primary dysmenorrhea. STUDY DESIGN: In this
      clinical trial, 44 girls with primary dysmenorrhea were randomly divided into
      intervention and control groups. Patients in the intervention group received 1500
      mg/day of chlorella as 5 soft gel and the control group received placebo soft
      gels for eight weeks. Menstrual and food information were collected using a
      previously validated and published questionnaire. Anthropometric measurements and
      biochemical parameters including prostaglandin E2 (PGE2), ProstaglandinF2a
      (PGF2a), high-sensitivity C-reactive protein (hs-CRP) and malondialdehyde (MDA)
      were assessed at baseline and end of week eight. RESULTS: In chlorella
      supplemented group the PGE2, PGF2a, hs-CRP and MDA decreased significantly (P <
      0.05). The severity and duration of dysmenorrheal pain were significantly reduced
      in the intervention group compared to the control group (p < 0.05). Systemic
      symptoms of dysmenorrhea (fatigue, headache, nausea, vomiting, lack of energy)
      decreased in the chlorella group (p < 0.05). The mean of menstrual
      characteristics, anthropometric indices and daily energy and macronutrient intake
      in both intervention and control groups were not changed significantly.
      CONCLUSION: This study showed that chlorella supplementation could decrease the
      severity of pain and systemic symptoms and improve serum levels of
      prostaglandins, inflammatory and oxidative markers in women with primary
      dysmenorrhea.

PMID- 30205316
TI  - The relationship between functionality and erector spinae activity in patients
      with specific low back pain during dynamic and static movements.
AB  - BACKGROUND: Alterations in the activity of the lumbar erector spinae (LES)
      muscles on both sides of the spine have been inconsistently reported in patients
      with specific low back pain (sLBP) after measuring the muscular activity with
      surface electromyography (sEMG). It also remains unclear whether these
      alterations in LES activity can be related to the functional level of patients
      with sLBP. RESEARCH QUESTION: This study investigated the LES activity in
      patients with sLBP during activities of daily living (ADL) which included dynamic
      and static movement tasks. Moreover, the alterations in LES activity were
      correlated with the first seven questions of the Zurich Claudication
      Questionnaire (ZCQ-SS). METHODS: Thirty patients with specific LBP and twenty
      healthy subjects were recruited to perform five ADLs including 'static waist
      flexion', 'sit to stand',' 30-seconds standing', '6-minutes walking' and
      'climbing stairs'. sEMG sensors were mounted on the left and right LES muscles.
      The integrated EMG (IEMG) was calculated from the preprocessed sEMG data as
      statistical comparison criteria. RESULTS: LES activity was significantly higher
      in patients during 'sit to stand',' 30-seconds standing' and 'climbing stairs'
      and significantly lower during 'static waist flexion' compared to healthy
      controls. All tasks showed a significant correlation with the ZCQ-SS score except
      for '6-minutes walking', whereby LES activity and ZCQ-SS score correspondingly
      increased during 'sit to stand' and 'climbing stairs' and the LES activity
      decreased with an increasing ZCQ-SS score during 'static waist flexion' and' 30
      seconds standing'. SIGNIFICANCE: There was a high correlation between alterations
      in LES activity and the level of functionality in LBP patients. However, the LES
      activity showed an opposite behavior during static and dynamic movement tasks.
      The methodology presented can be a useful tool for quantifying improvements in
      functionality after rehabilitation processes.

PMID- 30205317
TI  - Early clinical evaluation of total hip arthroplasty by three-dimensional gait
      analysis and muscle strength testing.
AB  - BACKGROUND: As improvement of gait is an important reason for patients to undergo
      total hip arthroplasty (THA) and they generally tend to evaluate its success
      based on postoperative walking ability, objective functional evaluation of
      postoperative gait is important. However, the patient's normal gait before
      osteoarthritis is unknown and the changes that will occur postoperatively are
      unclear. We investigated the change in gait and hip joint muscle strength after
      THA by using a portable gait rhythmograph (PGR) and muscle strength measuring
      device. PATIENT AND METHODS: The subjects were 46 women (mean age: 65.9 years)
      with osteoarthritis of the hip. Gait analysis and muscle strength testing were
      performed before THA, as well as 3 weeks and 3 months after surgery. We measured
      the walking speed, step length, and gait trajectory using PGR prospectively. PGR
      is attached to the patient's waist and records signals at a sampling rate of 100
      Hz. Isometric torque of hip flexion and abduction were measured by using a hand
      held dynamometer. RESULTS: There was no improvement at 3 weeks postoperatively,
      but the walking speed, stride length and muscle strength were clearly showed
      improvement at 3 months postoperatively. The walking trajectory was not normal
      preoperatively, since the trajectory was not symmetrical and did not intersect in
      the midline or form a butterfly pattern, and abnormality of the trajectory tended
      to persist postoperative 3 months despite resolution of hip joint pain after
      surgery. CONCLUSION: Since postoperative improvement of gait is an important
      consideration for patients undergoing THA, it seems relevant to evaluate changes
      in the gait after surgery and three-dimensional analysis with a PGR may be useful
      for this purpose.

PMID- 30205319
TI  - Long non-coding RNA nuclear-enriched abundant transcript 1 inhibition blunts
      myocardial ischemia reperfusion injury via autophagic flux arrest and apoptosis
      in streptozotocin-induced diabetic rats.
AB  - BACKGROUND AND AIMS: This study aimed to investigate the effects of long non
      coding RNA (lncRNA)-nuclear-enriched abundant transcript (Neat1) on myocardial
      ischemia reperfusion injury in diabetic rats ex vivo and in vivo. METHODS:
      Screening for LncRNA Neat1 expression was performed in rat myocardial tissues
      using microarray analysis and verified by qRT-PCR. Cell viability of rat
      cardiomyocytes was analyzed by MTT assay. Levels of autophagy-related proteins
      Atg7, Atg5, LC3-II/LC3-I and p62 were determined by Western blot assay. Left
      ventricular end diastolic diameter (LVEDD), left ventricular end systolic
      diameter (LVESD), left ventricular ejection fraction (LVEF) and fractioning
      shortening were obtained by transthoracic echocardiography. Left ventricular end
      systolic pressure (LVESP), left ventricular end diastolic pressure (LVEDP),
      maximum rate of increase or decrease of left ventricular pressure (+/-dp/dtmax)
      and heart rate were obtained by computer algorithms and an interactive
      videographics programme. Myocardial infarct size was determined by Evans blue and
      triphenyltetrazolium chloride (TTC) staining. Myocardial apoptotic index was
      analyzed by TUNEL assay and immunohistochemical staining. Autophagic flux was
      examined by evaluating fluorescent LC3 puncta. RESULTS: Neat1 was highly
      expressed in ischemia reperfusion-treated diabetic rat myocardial tissues.
      Overexpression of Neat1 promoted the production of lactate dehydrogenase,
      inhibited superoxide dismutase content and cardiomyocyte viability. Neat1
      overexpression also promoted the production of serum myocardial enzymes,
      including creatine kinase and creatine kinase-MB, and increased infarct size. By
      promoting myocardial apoptosis and autophagy, Neat1 aggravated myocardial
      ischemia reperfusion (I/R) injury in diabetic rats. Neat1 promoted cardiomyocyte
      autophagy by up-regulating Foxo1 expression to increase hypoxia-reoxygenation
      injury. CONCLUSIONS: I/R treatment caused more injuries in diabetic rats compared
      with normal rats. Elevated Neat1 expression aggravates myocardial ischemia
      reperfusion injury via activation of apoptosis and autophagy in diabetic rats.
      Foxo1 is one of the molecular mechanisms underlying Neat1-induced autophagy.

PMID- 30205318
TI  - The prevalence, circumstances and consequences of unintentional falls among
      elderly Iranians: A population study.
AB  - BACKGROUND AND AIM: Falling threatens the health, independence and quality of
      life of older adults. Information about characteristics and predisposing factors
      of falls is essential to develop and implement effective preventing measure. The
      aim of this study was to examine the prevalence, circumstances and consequences
      of falls among community-dwelling older adults in Tehran, Iran, and scrutinize
      factors (e.g. demographics) associated with falls. METHODS: A cross-sectional
      study was conducted in Tehran. A total of 653 individuals aged 65 years and over
      were selected by a stratified random sampling as representing older adults in
      Tehran. All required data were collected through face-to-face interviews using
      questionnaires. RESULTS: The prevalence of falls was 39.7% and higher in women
      than in men. For both sexes, most of the falls occurred in the afternoon (n =
      135, 52.1%) and at home (n = 209, 80.7%). One-fourth of the falls (23.2%)
      occurred in a forward direction, mostly among women (60%). For both sexes, one
      third of the causes of falls were loss of balance, mostly among women and the
      oldest persons. Two-hundred and twelve of the fallers reported injuries. The
      logistic regression showed that female gender, low education and constant worries
      about living expenses were significantly associated with falls. CONCLUSIONS: This
      study may have provided new insights into the characteristics/ circumstances/
      consequences of injurious falls and their relation with age, gender and injury
      severity in Iran. It may be useful for health policy makers and health providers
      when designing falls intervention and prevention programs at the community level.

PMID- 30205322
TI  - Isofraxidin inhibits interleukin-1beta induced inflammatory response in human
      osteoarthritis chondrocytes.
AB  - Osteoarthritis (OA) is the most prevalent disease of knee especially in the aged
      people. Isofraxidin (IF) is a coumarin compound refined from traditional Chinese
      medicines with potential anti-inflammatory ability. This study aimed to evaluate
      protective anti-inflammatory effects of IF in human OA chondrocytes. The
      chondrocytes were isolated from OA patients and pretreated with IF before
      treatment with IL-1beta. The results showed that IF blocked IL-1beta-stimulated
      production of NO and PGE2. In addition, IF inhibited the expression of COX-2,
      iNOs, MMP-1, MMP-3, MMP-13, ADAMTS-4 and ADAMTS-5, and increased the levels of
      aggrecan and collagen-II. Mechanistically, IF suppressed IL-1beta-induced IkappaB
      alpha degradation and NF-kappaB activation. In conclusion, our results
      demonstrate that IF inhibits inflammation in OA via the regulation of NF-kappaB
      signaling, and suggest that IF may be a potential therapeutic agent for OA.

PMID- 30205320
TI  - Long- and short-term air pollution exposure and measures of arterial stiffness in
      the Framingham Heart Study.
AB  - BACKGROUND: Studies of air pollution exposure and arterial stiffness have
      reported inconsistent results and large studies employing the reference standard
      of arterial stiffness, carotid-femoral pulse-wave velocity (CFPWV), have not been
      conducted. AIM: To study long-term exposure to ambient fine particles (PM2.5),
      proximity to roadway, and short-term air pollution exposures in relation to
      multiple measures of arterial stiffness in the Framingham Heart Study. METHODS:
      We assessed central arterial stiffness using CFPWV, forward pressure wave
      amplitude, mean arterial pressure and augmentation index. We investigated long
      and short-term air pollution exposure associations with arterial stiffness with
      linear regressions using long-term residential PM2.5 (2003 average from a
      spatiotemporal model using satellite data) and proximity to roadway in addition
      to short-term averages of PM2.5, black carbon, particle number, sulfate, nitrogen
      oxides, and ozone from stationary monitors. RESULTS: We examined 5842
      participants (mean age 51 +/- 16, 54% women). Living closer to a major roadway
      was associated with higher arterial stiffness (0.11 m/s higher CFPWV [95% CI:
      0.01, 0.22] living <50 m vs 400 <= 1000 m). We did not observe association
      between arterial stiffness measures and long-term PM2.5 or short-term levels of
      PM2.5, particle number, sulfate or ozone. Higher levels of black carbon and
      nitrogen oxides in the previous days were unexpectedly associated with lower
      arterial stiffness. CONCLUSIONS: Long-term exposure to PM2.5 was not associated
      with arterial stiffness but positive associations with living close to a major
      road may suggest that pollutant mixtures very nearby major roads, rather than
      PM2.5, may affect arterial stiffness. Furthermore, short-term air pollution
      exposures were not associated with higher arterial stiffness.

PMID- 30205321
TI  - Dentine biomarkers of prenatal and early childhood exposure to manganese, zinc
      and lead and childhood behavior.
AB  - BACKGROUND: Metal exposure alters neurodevelopmental outcomes; little is known
      about critical windows of susceptibility when exposure exerts the strongest
      effect. OBJECTIVE: To examine associations between dentine biomarkers of
      manganese (Mn), zinc (Zn) and lead (Pb) and later childhood behaviors. METHODS:
      Subjects enrolled in a longitudinal birth cohort study in Mexico City provided
      naturally shed deciduous teeth. We estimated weekly prenatal and postnatal
      dentine Mn, Zn and Pb concentrations in teeth using laser ablation-inductively
      coupled plasma-mass spectrometry (LA-ICP-MS) and measured behavior at ages 8-11
      years of age using the Behavior Assessment System for Children, 2nd edition (BASC
      2). We used distributed lag models and lagged weighted quantile sum regression to
      identify the role of individual and combined dentine biomarkers of Mn, Zn and Pb
      on behavioral outcomes controlling for maternal education and gestational age.
      RESULTS: Among the 133 subjects included in this study, prenatal and early
      postnatal dentine Mn appeared protective against childhood behavioral problems,
      specifically hyperactivity and attention. Postnatal dentine Mn was associated
      with increased reporting of internalizing problems, specifically anxiety. At 6
      months, a 1-unit increase (unit = 1 SD of log concentration) in Mn was associated
      with a 0.18-unit (unit = 1 SD of BASC-2 score) increase in internalizing symptoms
      score and a 0.25-unit increase in anxiety. Postnatal Pb was associated with
      increasing anxiety symptoms; at 12 months, a 1-unit increase in Pb was associated
      with a 0.4 unit increase in anxiety symptoms. When examined as a metal mixture,
      we observed two potential windows of susceptibility to increased anxiety
      symptoms: the first window (0-8 months) appeared driven by Mn, the second window
      (8-12 months) was driven by the metal mixture and dominated by Pb. A 1-unit
      increase in the mixture index was associated with a 0.7-unit increase in SD of
      anxiety symptoms. CONCLUSIONS: Childhood behaviors may demonstrate postnatal
      windows of susceptibility to individual and mixed metal concentrations measured
      in deciduous teeth. Prenatal dentine Mn may be protective, while excessive early
      postnatal Mn may increase risk for adverse behaviors. In combination, higher
      concentrations of Mn, Zn and Pb may have an adverse impact on behavior.

PMID- 30205324
TI  - The failure of polypropylene surgical mesh in vivo.
AB  - Surgical mesh materials made from fibres of polypropylene (PP) have been widely
      used for over fifty years. However in recent times the use of these materials has
      been called into question for certain surgical operations, known as "pelvic
      organ" or "transvaginal" procedures. This article reviews the current state of
      knowledge and uses some simple biomechanics analysis in order to make
      recommendations for future work. My conclusion is that the failure rate of PP
      mesh in pelvic organ products is unacceptably high whilst being much lower when
      it is used for hernia repair. The precise mechanical environment is difficult to
      quantify but a tentative conclusion is that failure by purely mechanical
      mechanisms (fatigue and creep) is unlikely. There is some evidence for
      environmental degradation (i.e. stress-corrosion) but this is highly contested in
      the literature. On balance my conclusion is that stress-corrosion failure is the
      most likely explanation but currently no experimental results exist to prove
      conclusively that this failure mechanism occurs in vivo. Further work is needed,
      especially the analysis of explanted material, to resolve this urgent problem.

PMID- 30205323
TI  - Sensory and descending motor circuitry during development and injury.
AB  - Proprioceptive sensory input and descending supraspinal projections are two major
      inputs that feed into and influence spinal circuitry and locomotor behaviors.
      Here we review their influence on each other during development and after spinal
      cord injury. We highlight developmental mechanisms of circuit formation as they
      relate to the sensory-motor circuit and its reciprocal interactions with local
      spinal interneurons, as well as competitive interactions between proprioceptive
      and descending supraspinal inputs in the setting of spinal cord injury.

PMID- 30205325
TI  - Breast implant surface texture impacts host tissue response.
AB  - BACKGROUND: Surface texture of a breast implant influences tissue response and
      ultimately device performance. Characterizing differences among available surface
      textures is important for predicting and optimizing performance. METHODS:
      Scanning electron microscopy (SEM) and X-ray computed tomography (CT)-imaging
      were used to characterize the topography and surface area of 12 unique breast
      implant surface textures from seven different manufacturers. Samples of these
      surface textures were implanted in rats, and tissue response was analyzed
      histologically. In separate experiments, the force required to separate host
      tissue from the implant surface texture was used as a measure of tissue
      adherence. RESULTS: SEM imaging of the top and cross section of the implant
      shells showed that the textures differed qualitatively in evenness of the
      surface, presence of pores, size and openness of the pores, and the depth of
      texturing. X-ray CT imaging reflected these differences, with the texture surface
      area of the anterior of the shells ranging from 85 to 551 mm2, which was 8-602%
      greater than that of a flat surface. General similarities based on the physical
      structure of the surfaces were noted among groups of textures. In the rat models,
      with increasing surface texture complexity, there was increased capsule
      disorganization, tissue ingrowth, and tissue adherence. CONCLUSIONS: Surface area
      and topography of breast implant textures are important factors contributing to
      tissue ingrowth and adherence. Based on surface area characteristics and
      measurements, it is possible to group the textures into four classifications:
      smooth/nanotexture (80-100 mm2), microtexture (100-200 mm2), macrotexture (200
      300 mm2), and macrotexture-plus (> 300 mm2).

PMID- 30205326
TI  - Visco-elasto-plastic modeling of small intestinal submucosa (SIS) for application
      as a vascular graft.
AB  - In developing new tissue engineered for vascular grafts, the mechanical
      properties of the material and its evolution once implanted are of utmost
      importance because they determine the regeneration of the vessel and the blood
      flow through the conduit. In fact, compliance mismatch is considered the main
      determinant of graft failure. In this research, we analyze the dynamic properties
      of the small intestinal submucosa (SIS), and propose and validate a constitutive
      model to fit the material's behavior. A uniaxial creep and recovery test was
      performed on SIS tubes to find the constitutive parameters. The model was
      composed by an elastic element in series with two Kelvin-Voigt solid elements and
      a plastic slider. The first elastic component was defined using Mooney-Rivlin
      strain energy function, while the plastic component was defined using a third
      degree polynomial function of the plastic stress. The viscoelastic behavior was
      defined using the creep compliance formulation for the Kelvin-Voigt model. The
      parameters for the plastic and non-linear elastic elements followed a normal
      distribution, while the spring and dashpot constants of the visco-elastic element
      had a linear dependence on the load applied. The constitutive model was then used
      to simulate the SIS under the geometrical and pressure conditions found in native
      vessels for 1000 cycles at a frequency of 60 cycles per minute. From the cases
      simulated, performance curve charts were obtained in terms of the compliance of
      the material. These curve charts can be used as a predictive tool of the graft's
      behavior based on its geometry.

PMID- 30205327
TI  - Effect of exogenous calcium on growth, nutrients uptake and plasma membrane H+
      ATPase and Ca2+-ATPase activities in soybean (Glycine max) seedlings under
      simulated acid rain stress.
AB  - Calcium (Ca) is one of essential elements for plant growth and development, and
      also plays a role in regulating plant cell physiology and cellular response to
      the environment. Here, we studied whether calcium played a role in enhancing
      tolerance of plants to acid rain stress by hydroponics and simulating acid rain
      stress. Our results show that acid rain (pH 4.5/pH 3.0) caused decreases in dry
      weight biomass, chlorophyll content and uptake of nutrients elements (NO3-, P, K,
      Mg, Zn and Mo) and an increase in membrane permeability of root. However, all
      parameters in soybean treated with exogenous calcium (5 mM) and acid rain at pH
      4.5 were closed to the control levels. In addition, exogenous calcium (5 mM)
      alleviated the inhibition induced by pH 3.0 acid rain on the activity of plasma
      membranes H+-ATPase and the expression of GmPHA1 at transcriptional level, being
      benefiting to maintaining uptake of nutrients (NO3-, P, K, Mg, and Zn), and then
      lower the decrease in dry weight biomass and chlorophyll content. After a 5-day
      recovery (without acid rain stress), all parameters in soybean treated with acid
      rain at pH 3.0 and exogenous calcium were still worse than those of the control,
      but obviously better than those treated with acid rain at pH 3.0. Higher activity
      of plasma membrane H+-ATPase in soybean treated with acid rain at pH 3.0 and
      exogenous calcium was good to uptake of nutrients and promoted the recovery of
      soybean growth, compared with soybean treated with acid rain at pH 3.0. In
      conclusion, exogenous calcium could alleviate the inhibition caused by acid rain
      on soybean growth by increasing the activity of plasma membrane H+-ATPase for
      providing driving force to nutrient absorption, and its regulating effect was
      limited by intensity of acid rain. Furthermore, the application of exogenous
      calcium can be one of ways to alleviate the damage caused by acid rain to plants.

PMID- 30205328
TI  - Dopamine receptor D2 gene polymorphism, urine fluoride, and intelligence
      impairment of children in China: A school-based cross-sectional study.
AB  - OBJECTIVE: We aimed to study the association of urine fluoride with intelligence
      quotient (IQ) in children with a careful consideration of up to 30 potential
      confounding factors as well as possible heterogeneity of the relation between
      urine fluoride levels and IQ scores across children with different dopamine
      receptor-2 (DRD2) Taq 1A genotypes (CC, CT, and TT). METHODS: A school-based
      cross-sectional study design was applied. A total of 323 children (2014-2015, 7
      12 years old) were enrolled from four schools in both historical endemic and non
      endemic areas of fluorosis in Tianjin of China using a cluster sampling method.
      Urine fluoride levels and age-specific IQ scores in children were measured at the
      enrollment. Polymerase chain reaction-restriction fragment length polymorphism
      methods were used to genotype DRD2 Taq 1A polymorphism with genomic DNA isolated
      from whole blood collected at the enrollment. Multiple linear regression models
      were applied to evaluate the relationship between urine fluoride levels and IQ
      scores overall and within the DRD2 Taq 1A SNP = CC/CT and TT subgroups. Model
      robustness was tested through bootstrap, sensitivity analysis, and cross
      validation techniques. A safety threshold of urine fluoride levels for IQ
      impairment was determined in the subgroup TT. RESULTS: In overall participants,
      the DRD2 Taq 1A polymorphism itself was not related to IQ scores in children who
      had a high level of urine fluoride. In the CC/CT subgroup, urine fluoride levels
      and IQ scores in children were unrelated (adjusted beta (95% confidence interval
      (CI)) = - 1.59 (- 4.24, 1.05), p = 0.236). Among the participants carrying the TT
      genotype, there was a strong and robust negative linear relationship between log
      urine fluoride and IQ scores in children (adjusted beta (95% CI) = - 12.31 (-
      18.69, - 5.94), p < 0.001). Urine fluoride levels had a stronger association with
      IQ in children carrying the TT genotype (adjusted beta = - 12.31, bootstrapped
      standard error (SE) = 1.28), compared to that in overall participants (adjusted
      beta = - 2.47, bootstrapped SE = 3.75) (Z = 2.483 and bootstrapped p = 0.007).
      The safety threshold of urine fluoride levels in the subgroup TT was 1.73 mg/L
      (95% CI = (1.51, 1.97) (mg/L)). CONCLUSIONS: There is heterogeneity in the
      relation between urine fluoride and IQ across children carrying different DRD2
      Taq 1A genotypes. Large-scale epidemiological studies are needed to confirm our
      findings.

PMID- 30205329
TI  - Laccase production from sucrose by recombinant Yarrowia lipolytica and its
      application to decolorization of environmental pollutant dyes.
AB  - Laccases are used in decolorization and biodegradation of synthetic dyes,
      bioremediation of industrial wastewaters and delignification of lignocellulosic
      compounds. The aims of the present study were the optimization of a recombinant
      laccase production in Yarrowia lipolytica yeast using sucrose as a main carbon
      source, and the application of the resulting enzyme to decolorization of
      synthetic dyes, which are problematic environmental pollutants. Taguchi's
      experimental design method was employed to optimize medium compounds. Recombinant
      laccase production by Y. lipolytica YL4 strain increased to 900 U L-1 after
      optimization of sucrose, ammonium chloride, yeast extract and thiamine levels in
      the modified PPB medium. Furthermore, the production rate reached 6760 U L-1 in a
      5 L bioreactor which represents 4.5- and 33.5-fold increases compared to cultures
      that were in shake-flask with optimized and primary media, respectively. The
      supernatant containing secreted recombinant laccase was applied for
      decolorization of seven dyes. The effects of pH, the amount of enzyme and
      incubation period were verified. The effect of incubation time on dye
      decolorization by recombinant laccase was important, which has an influence of
      greater extent than 90% after 48 h for all dyes. The Trametes versicolor laccase
      can be efficiently produced in Y. lipolytica and the recombinant enzyme has a
      considerable potential in the decolorization of pollutant synthetic dyes.

PMID- 30205330
TI  - Mixture toxicity assessment of a biocidal product based on reproduction and
      avoidance behaviour of the collembolan Folsomia candida.
AB  - Biocidal products represent mixtures that might be released into the environment
      at application and continuously during service life. Concentration addition (CA)
      has been proposed as default model to calculate theoretical mixture toxicity.
      However, the suitability of CA for chronic toxicity towards soil organisms has so
      far rarely been evaluated and therefore needs further experimental evidence. The
      present study investigated the toxicity of a wood preservative product and the
      individual active substances (tebuconazole and IPBC) therein with the aim to
      evaluate the compliance with the CA prediction for the product. Folsomia candida
      was selected as test organism for this purpose using the endpoints reproduction
      and avoidance behaviour. Both endpoints were increasingly impacted by increasing
      concentrations of the wood preservative product as well as its active substances
      tested individually. The chronic effects of the product could be predicted by CA
      with less than 4-fold deviation, while the assessment for avoidance behaviour
      indicated a strong underestimation. This underestimation could not be attributed
      to the one known formulation additive, an organic solvent. Overall, the present
      study provides some more evidence that CA could be applied as default model for
      standard endpoints of soil organisms, but warns against using CA for behavioural
      responses.

PMID- 30205331
TI  - Effect of ionic strength on bioaccumulation and toxicity of silver nanoparticles
      in Caenorhabditis elegans.
AB  - The behavior of silver nanoparticles (AgNPs) is influenced by environmental
      factors which altered their bioaccumulation and toxicity. In this study, we
      comprehensively investigated the influence of ionic strength on the ecotoxicity
      of AgNPs to Caenorhabditis elegans (C. elegans) through the transfer from
      Escherichia coli (E. coli). Three different exposure media (deionized water, EPA
      water and KM) were used to pretreat AgNPs. E. coli was then exposed to these
      transformed AgNPs and fed to C. elegans. Our results indicated that ionic
      strength significantly enhanced the reproductive toxicity (germ cell corpses,
      brood size and lifespan) and neurotoxicity (head trash and body bend) of AgNPs in
      C. elegans. Moreover, ICP-MS analysis showed that higher ionic strength increased
      bioaccumulation of AgNPs in E. coli and the resulting Ag body burden of E. coli
      affected the transfer of AgNPs to C. elegans, which might be responsible for the
      increased toxicity to nematodes. Furthermore, we also found that the reactive
      oxygen species (ROS) level in C. elegans was significantly increased after
      exposed to E. coli contaminated with ionic strength-treated AgNPs, which might
      play another important role for the enhanced toxicity of AgNPs. Overall, this
      study showed that the bioavailability and potential ecotoxicity of AgNPs are
      associated with the environmental factors.

PMID- 30205332
TI  - Tannic acid functionalized graphene hydrogel for organic dye adsorption.
AB  - Water purification provides a feasible way to relieve the pressure of water
      shortage and water pollution which we are facing and adsorption is one of the
      most effective ways to turn polluted water into clean water. Here, we prepared
      graphene-tannic acid hydrogel using graphene oxide and tannic acid, a natural
      green reducer and adsorbent, through one-step hydrothermal method. The
      composition, structure, and morphology of the compounds were systematically
      examined. The adsorption of dyes was mainly influenced by the morphology and
      chemical properties of gel. The addition of tannic acid, a molecule rich in
      oxygen containing functional groups, changed the surface chemistry of graphene
      sheets and microstructures of gels, which was beneficial for contaminate
      adsorption. Compared with reduced graphene oxide hydrogel, the graphene-tannic
      acid hydrogel showed an outstanding adsorption capacity for organic dye methylene
      blue, more than 500 mg/g at pH 10 and the maximum adsorption capacity was up to
      714 mg/g. After adsorption, ethanol and inorganic acid solution can be used as
      desorption agent and there was no significant adsorption capacity loss after 5
      cycles.

PMID- 30205334
TI  - Computer-aided classification of prostate cancer grade groups from MRI images
      using texture features and stacked sparse autoencoder.
AB  - A novel method to determine the Grade Group (GG) in prostate cancer (PCa) using
      multi-parametric magnetic resonance imaging (mpMRI) biomarkers is investigated in
      this paper. In this method, high-level features are extracted from hand-crafted
      texture features using a deep network of stacked sparse autoencoders (SSAE) and
      classified them using a softmax classifier (SMC). Transaxial T2 Weighted (T2W),
      Apparent Diffusion Coefficient (ADC) and high B-Value Diffusion-Weighted (BVAL)
      images obtained from PROSTATEx-2 2017 challenge dataset are used in this
      technique. The method was evaluated on the challenge dataset composed of a
      training set of 112 lesions and a test set of 70 lesions. It achieved a quadratic
      weighted Kappa score of 0.2772 on evaluation using test dataset of the challenge.
      It also reached a Positive Predictive Value (PPV) of 80% in predicting PCa with
      GG > 1. The method achieved first place in the challenge, winning over 43 methods
      submitted by 21 groups. A 3-fold cross-validation using training data of the
      challenge was further performed and the method achieved a quadratic-weighted
      kappa score of 0.2326 and Positive Predictive Value (PPV) of 80.26% in predicting
      PCa with GG > 1. Even though the training dataset is a highly imbalanced one, the
      method was able to achieve a fair kappa score. Being one of the pioneer methods
      which attempted to classify prostate cancer into 5 grade groups from MRI images,
      it could serve as a base method for further investigations and improvements.

PMID- 30205333
TI  - Mortality and morbidity due to exposure to ambient particulate matter.
AB  - The aim of this study was to investigate spatial variation and health risk of the
      exposure to PM2.5 (particulate matter with a diameter of 2.5 um or less) and PM10
      (particulate matter with a diameter of 10 um or less) in Sabzevar, Iran. PM2.5
      and PM10 were measured during three campaigns from April to November 2017, in 26
      sampling points. Spatial analysis was performed using kriging and
      autocorrelations (Moran's index) model in Arc GIS software. Relationship between
      exposure to the PM2.5 and PM10 and their health impacts were investigated by AirQ
      2.2.3 software. The mean concentrations (and standard deviation) of PM 2.5 and
      PM10 over the entire study period were 32.54 (37.28) and 42.61 (47.76) MUg/m3,
      respectively, which were higher than the guideline of World Health Organization.
      According to the spatial analysis, the maximum concentrations of PM2.5 and PM10
      were around the main highway (beltway) which placed all over the south of
      Sabzevar. According to the Moran's index, the emission patterns for PM2.5 (Z
      score = 2.53; P-value = 0.011) and PM10 (Z-score = 2.82; P-value = 0.004) were
      clustered. The attributable percentage (AP) of total mortality related to PM2.5
      and PM10 were 3.544% (95% confidence interval (CI): 2.623-4.447%) and 2.055% (95%
      CI: 1.379-2.721%) per increasing each 10 MUg/m3 of these pollutants,
      respectively. According to observed results, it is suggested that the beltway and
      other pollution sources, such as industries, should be placed at a greater
      distance from the city, to reduce PM amounts in residential areas.

PMID- 30205335
TI  - Hydrogel bowls for cleaning oil spills on water.
AB  - We demonstrate a hydrogel bowl capable of selectively and rapidly collecting
      spilled oil while floating on water. The bowl has macroscopic openings in its
      sidewall, and its surface is first coated with octadecyltrichlorosilane (OTS) and
      then with diffusion pump oil, which imparts exceptional hydrophobic, oleophilic,
      and high oil wettability properties. The use of a hydrogel makes it possible to
      obtain surface hydrophobicity and oleophilicity, while also being inexpensive,
      eco-friendly, and easy to fabricate. Using a prototype of the bowl and a small
      pump system, we demonstrate that oils with a broad range of viscosities (2.7
      2000.0 cSt at 20-40  degrees C) are more rapidly and efficiently collected from
      the surface of both pure water and seawater than with any other reported
      technique. The hydrogel bowl can collect oil for more than one month without
      losing its efficiency and can be stored in oil for reuse. Therefore, such
      hydrogel bowls represent a new alternative to conventional oil spill remediation
      techniques.

PMID- 30205336
TI  - Upgrading liquor-making wastewater into medium chain fatty acid: Insights into co
      electron donors, key microflora, and energy harvest.
AB  - Ethanol and lactate are considered suitable electron donors (EDs) for chain
      elongation (CE); however, their respective shortcomings still limit the substrate
      conversion ratio and medium chain fatty acid (MCFA) production. To address this
      limitation, different EDs and electron acceptors (EAs) were combined to compare
      their CE performances, and to investigate whether the combination of ethanol and
      lactate could further enhance the MCFA production based on the complementary
      characteristics of ethanol and lactate. The results verified, for the first time,
      ethanol and lactate as the co-EDs formed a cooperative relationship to largely
      promote the conversion of substrates into MCFA. The co-EDs of ethanol and lactate
      stimulated the transformation of dispersive lactate-carbon flux from the
      competing acrylate pathway into n-heptylate. Additionally, the coexisting by
      products (H2 and CO2) from ethanol and lactate also contributed to the
      supererogatory MCFA generation. The key microbial taxa that distinguished the co
      EDs from their single action were the preponderant species from class
      Negativicutes and family Ruminococcaceae. In addition, the co-EAs of acetate, n
      butyrate, and n-caproate also promoted MCFA generation. Low concentration of n
      caproate could be directly elongated into n-caprylate, while n-caproate
      concentration exceeding the toxic limit was unsuitable as an EA. This research
      provided a guide for substrate selection and collocation for CE technology.
      Chinese liquor-making wastewater (CLMW) was subsequently used as a substrate for
      MCFA production since it contains abundant lactate, ethanol, and short-chain
      fatty acids. In this study, a MCFA selectivity of 80.34 +/- 5.26%, a slightly
      higher selectivity which is in the range of previously reported ones, was
      obtained. This study paves a way for the sustainable development of Chinese
      liquor industry by recycling the high-output CLMW into MCFA.

PMID- 30205337
TI  - Enhancing soluble phosphate concentration in sludge liquor by pressurised
      anaerobic digestion.
AB  - Recovery of phosphate from wastewater is challenging, with one of the best
      opportunities being recovery from sludge anaerobic digestion liquor, as struvite.
      However, this is limited by the proportion of total phosphorous which is soluble,
      due to in-digester metal ion precipitation. High-pressure anaerobic digestion may
      enable enhanced phosphate solubility (and hence recovery potential), without the
      use of added acid, due to an increased liquid phase CO2 concentration. This was
      tested at 2, 4, and 6 bar absolute (bara) vs a 1 bara control reactor, fed with
      activated sludge. Increased pressure significantly (p = 0.0008), increased the
      fraction of phosphate that was soluble, ranging from 52% at 1 bara, to 75% at 6
      bara. Model based analysis indicated that the main reason for increased
      solubility was pH depression (down to 6.4 at 6 bara), rather than changes in ion
      pairing (with carbonates) or increases in ionic activity. However, biological
      performance was adversely impacted, with a substantial loss in VS and COD
      destruction (on the order of 5%-10% absolute). No organic acid accumulation was
      observed. Bacterial and archaeal communities were significantly impacted
      (p~0.0003-0.0005), with a shift to specific organisms, including Bacteroidales
      Rikenellaceae within the bacteria, and a Deep Sea Euryarchaeotal Group at 2 bara,
      and Methanocellaceae within the archaea at 4 and 6 bara. The work indicates that
      high-pressure operation is a technically viable option to improve phosphate
      recovery, and produce a high-methane biogas product, but that the loss of overall
      conversion needs to be further addressed, possibly through two-stage digestion.

PMID- 30205338
TI  - Modeling emerging contaminants breakthrough in packed bed adsorption columns by
      UV absorbance and fluorescing components of dissolved organic matter.
AB  - This study investigated, using rapid small-scale column testing, the breakthrough
      of dissolved organic matter (DOM) and eleven emerging organic contaminants (EOCs)
      during granular activated carbon (GAC) filtration of different water qualities,
      including wastewater, surface water and synthetic water (riverine organic matter
      dissolved in deionized water). Fluorescing organic matter was better adsorbed
      than UV absorbance at 254 nm (UV254) and dissolved organic carbon (DOC) in all
      tested water. Furthermore, highest adsorption of DOM (in terms of DOC, UV254 and
      fluorescence) was observed during wastewater filtration. UV absorbing DOM had
      fast and similar breakthrough in surface water and synthetic water, whereas
      fluorescence breakthrough was very rapid only in synthetic water. PARAFAC
      modeling showed that different fluorescing components were differently adsorbed
      during GAC process. Particularly, fluorescing components with maxima intensity at
      higher excitation wavelengths, which are corresponding to humic-like fluorescence
      substances, were better removed than other components in all waters. As opposed
      to DOM, EOCs were better adsorbed during synthetic water filtration, whereas the
      fastest EOCs breakthrough was observed during filtration of wastewater, which was
      the water that determined the highest carbon fouling. Exception was represented
      by long-chained perfluoroalkylated substances (i.e., PFOA, PFDA and PFOS).
      Indeed, adsorption of these compounds resulted independent of water quality. In
      this study was also investigated the applicability of UV254 and fluorescing
      PARAFAC components to act as surrogates in predicting EOCs removal by GAC in
      different water matrices. Empirical linear correlation for the investigated EOCs
      were determined with UV254 and fluorescing components in all water qualities.
      However, fluorescence measurements resulted more sensitive than UV254 to predict
      EOC breakthrough during GAC adsorption. When the data from all water qualities
      was combined, good correlations between the microbial humic-like PARAFAC
      component and EOC removals were still observed and they resulted independent of
      water quality if considering only real water matrices (wastewater and surface
      water). On the contrary, correlations between EOC removals and UV254 removals
      were independent of water quality when combining data of surface waters and
      synthetic water, but a different correlation model was needed to predict EOCs
      breakthrough in wastewater.

PMID- 30205339
TI  - Marine microorganisms for synthesis of metallic nanoparticles and their
      biomedical applications.
AB  - Nanotechnology has become one of the most in demand technologies applied in
      different fields of science. Metallic nanoparticles synthesis using marine
      microorganisms has been received global attention due to their extensive
      applications in biomedical science. The use of marine microbes for metallic
      nanoparticles synthesis is eco-friendly, time saving, and inexpensive. An eco
      friendly method is essential to minimize waste and protect environment. Recently,
      marine microorganisms are recognized an eco-friendly and efficient way to utilize
      as potential biofactories for synthesis of metallic nanoparticles. Here, we
      discuss and detail the possible uses of different marine microorganisms including
      bacteria, fungi and microalgae for metallic nanoparticle synthesis and those
      nanoparticles applications as antimicrobial and anticancer agents. In addition,
      different parameters that cause changes on nanoparticles shape and morphology are
      also highlighted.

PMID- 30205340
TI  - Preparation and study of the antibacterial ability of graphene oxide-catechol
      hybrid polylactic acid nanofiber mats.
AB  - The functionalization of electrospun mats with antimicrobial nanomaterials is an
      attractive strategy when developing functional graphene oxide coating materials
      to prevent bacterial colonization on surfaces. In this study, we demonstrated a
      simple approach to produce antimicrobial electrospun mats by dip-coating a
      polylactic acid (PLA) nanofiber into a graphene oxide-catechol derivative. PLA
      was first electrospun to yield narrow-diameter polymeric nanofibers. We then
      modified the graphene oxide (GO) with a catechol derivative - dopamine
      methacrylamide monomer (DMA) - to synthesize a GO-DMA nanocomposite material
      which exhibited robust antimicrobial properties. The catechol groups promote the
      immobilization of graphene oxide onto the PLA nanofibers and possess strong
      antimicrobial properties. We therefore selected this functional group to modify
      GO. We dipped the GO-DMA onto the PLA nanofiber to produce the final
      functionalized electrospun mats. The PLA mats which were functionalized using the
      GO-DMA nanocomposite (PLA-GO-DMA) displayed antibacterial activity against both
      Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus)
      bacteria. Furthermore, we studied the biocompatibility of the mats by culturing
      the cell lines (HepG2, A549, and HUVEC-C) of PLA-GO-DMA among the nanofibers
      which exhibited excellent biocompatibility. These results collectively
      demonstrate the potential of PLA-GO-DMA nanofiber mats as antimicrobial
      biomaterials and provide fundamental information toward the establishment of
      future biomedical applications.

PMID- 30205341
TI  - Vegetation distribution along mountain environmental gradient predicts shifts in
      plant community response to climate change in alpine meadow on the Tibetan
      Plateau.
AB  - Plants are particularly sensitive to climate change in alpine ecosystem of the
      Tibetan Plateau. The various mountain micro-climates provide a natural gradient
      for space-for-time substitution research that plant responses to climate change.
      In this study, we surveyed the plant community in term of species composition,
      diversity and biomass across 189 sites on a hill of the Tibetan Plateau and
      analysed the individual and integrated effects of soil temperature and moisture
      on the plant community. The results showed that, at the quadrat scale, there were
      decrease in richness of 1.08 species for every 1  degrees C increase in soil
      temperature and 3.56 species for every 10% decrease in soil moisture. The
      integrated effects of increasing soil temperature and decreasing moisture are
      expected to lead to a rapid decrease in species richness. Biomass had no
      significant correlation with soil temperature but significantly decreased with
      soil moisture decreasing (p < 0.01). Biomass would decrease when soil moisture
      was below 20%, no matter how the change of soil temperature. We also found that
      gramineae and perennial forbs were sensitive to climate change. With soil
      temperature increased, the proportion of gramineae increased, whereas the
      proportion of perennial forbs decreased. The integrated effects of soil
      temperature increasing and moisture decreasing caused a shift from sedge
      controlled to gramineae-controlled communities in alpine meadow. This study not
      only enhances our understanding of mountain plant community dynamics under
      climate change, but also predicts the shift of vegetation response to climate
      change on high-elevation alpine meadow.

PMID- 30205342
TI  - Normalizing land surface temperature for environmental parameters in mountainous
      and urban areas of a cold semi-arid climate.
AB  - Normalization of land surface temperature (LST) relative to environmental factors
      is of great importance in many scientific studies and applications. The purpose
      of this study was to develop physical models based on energy balance equations
      for normalization of satellite derived LST relative to environmental parameters.
      For this purpose, a set of remote sensing imagery, meteorological and climatic
      data recorded in synoptic stations, and soil temperatures measured by data
      loggers were used. For modeling and normalization of LST, a dual-source energy
      balance model (dual-EB), taking into account two fractions of vegetation and
      soil, and a triple -source energy balance model (triple-EB), taking into account
      three fractions of vegetation, soil and built-up land, were proposed with either
      regional or local optimization strategies. To evaluate and compare the accuracy
      of different modeling results, correlation coefficients and root mean square
      difference (RMSE) were computed between modeled LST and LST obtained from
      satellite imagery, as well as between modeled LST and soil temperature measured
      by data loggers. Further, the variance of normalized LST values was calculated
      and analyzed. The results suggested that the use of local optimization strategy
      increased the accuracy of the normalization of LST, compared to the regional
      optimization strategy. In addition, no matter the regional or local optimization
      strategy was employed, the triple-EB model out-performed consistently the dual-EB
      model for LST normalization. The results show the efficiency of the local triple
      EB model to normalize LST relative to environmental parameters. The correlation
      coefficients were close to zero between all of the environmental parameters and
      the normalized LST. In other words, normalized LST was completely independent of
      the environmental parameters considered by this research.

PMID- 30205343
TI  - Determination of nanoparticle heteroaggregation attachment efficiencies and rates
      in presence of natural organic matter monomers. Monte Carlo modelling.
AB  - Understanding the transformation and transport of manufactured nanoparticles
      (NPs) in aquatic systems remains an important issue due to their potential
      hazard. Once released in aquatic systems, NPs will interact with natural
      compounds such as suspended inorganic particles and/or natural organic matter
      (NOM) and heteroaggregation will control their ultimate fate. Unfortunately,
      systematic experimental methods to study heteroaggregation are not
      straightforward and still scarce. In addition, the description of
      heteroaggregation rate constants and attachment efficiencies is still a matter of
      debate since no clear definition exists. In this work, an original cluster
      cluster Monte Carlo model is developed to get an insight into heteroaggregation
      process descriptions. A two-component system composed of NPs and NOM fulvic acid
      monomers is investigated by considering several water models to cover a range of
      (relevant) conditions from fresh to marine waters. For that purpose, homo- and
      hetero- individual attachment efficiencies between NPs and NOM units are adjusted
      (NP-NP, NOM-NOM and NP-NOM). The influence of NP/NOM ratio, NOM-NOM
      homoaggregation versus heteroaggregation, and surface coating effects is studied
      systematically. From a quantitative point of view, aggregation rate constants as
      well as attachment efficiencies are calculated as a function of physical time so
      as to characterize the individual influence of each parameter and to allow future
      comparison with experimental data. Heteroaggregation processes and global
      attachment efficiencies corresponding to several mechanisms and depending on the
      evolution of heteroaggregate structures all along the simulations are defined.
      The calculation of attachment efficiency values is found dependent on NP/NOM
      concentration ratios via coating effects, by the initial set of elementary
      attachment efficiencies and influence of homoaggregation. Marine water represents
      a specific case of aggregation where all particle contacts are effective. On the
      other hand, in "ultrapure" and "fresh waters", a competition between homo- and
      heteroaggregation occurs depending on the initial attachment efficiencies
      therefore indicating that a subtle change in the NP surface properties as well as
      in the water chemistry have a significant impact on heteroaggregation processes.

PMID- 30205344
TI  - Mitigating arsenic accumulation in rice (Oryza sativa L.) from typical arsenic
      contaminated paddy soil of southern China using nanostructured alpha-MnO2: Pot
      experiment and field application.
AB  - Manganese oxides are naturally occurring powerful oxidants and scavengers, which
      can control the mobility and bioavailability of arsenic (As). However, the effect
      of synthetic nanostructured manganese oxides on the mobilization and
      transportation of As at actual paddy soils are poorly understood, especially in
      soils with low or medium background Mn concentration. In the present study, a
      novel nano manganese oxide with superior reactivity and surface area has been
      synthesized. A 90-d soil incubation experiment combined with pot and field rice
      cultivation trials were designed to evaluate the effectiveness of exogenous alpha
      MnO2 nanorods on the mobilization and transportation of As in soil-rice systems.
      Our results proved that the addition of alpha-MnO2 nanorods can effectively
      control the soil-to-solution partitioning of As under anaerobic conditions. After
      treatment with different amounts of alpha-MnO2 nanorods, the content of effective
      As decreased, offset by an increase in residual As and insoluble binding As (Ca
      As and Fe-As). Enhancing the oxidation of As(III) into As(V), the alpha-MnO2
      nanorods increased the adsorption of As onto indigenous iron (hydr)oxides which
      greatly reduced the soil porewater As content. In addition, pot experiments and
      field applications revealed that the influx of As into the aerial parts of rice
      plants (stems, husk and leaves) was strictly prohibited after treatments with
      different amount of alpha-MnO2 nanorods; more interestingly, significantly
      negative correlations have been observed between As and Mn in rice, which
      indicated that as Mn is increased in soil, As in brown rice decreases. Our
      results demonstrated that the use of alpha-MnO2 nanorods in As polluted paddy
      soil containing low levels of background Mn oxides can be a promising remediation
      strategy.

PMID- 30205345
TI  - Parental co-exposure to bisphenol A and nano-TiO2 causes thyroid endocrine
      disruption and developmental neurotoxicity in zebrafish offspring.
AB  - The coexistence of organic toxicants and nanoparticles in the environment
      influences pollutant bioavailability and toxicity. Using chronic co-exposure to
      an adult zebrafish model, this study investigated the transfer kinetics and
      transgenerational effects of bisphenol A (BPA) and titanium dioxide nanoparticles
      (n-TiO2) exposure in F1 offspring. When single and combined exposure to BPA (0,
      2, and 20 MUg/L) and n-TiO2 (100 MUg/L) were compared, combined exposure was
      found to reciprocally facilitate bioaccumulation in adult fish while enhancing
      maternal transfer to offspring. Thyroid endocrine disruption and developmental
      neurotoxicity were observed in larval offspring by parental exposure to BPA alone
      or in combination with n-TiO2. Exposure to 20 MUg/L BPA significantly decreased
      the thyroxine (T4) concentration in adult plasma, leading to less transfer into
      the eggs. The presence of 20 MUg/L BPA with n-TiO2 further decreased the level of
      T4 compared to BPA exposure alone. Additionally, offspring larvae derived from
      exposed parents exhibited lethargic swimming behavior. Overall, this study
      examined the interactions of BPA and n-TiO2 with regard to their bioaccumulation,
      maternal transfer, and developmental effects, which highlighted that co-exposure
      dynamics are important and need to be considered for accurate environmental risk
      assessment.

PMID- 30205346
TI  - Inorganic ion chemistry of local particulate matter in a populated city of North
      China at light, medium, and severe pollution levels.
AB  - Twenty-six pairs of PM2.5 and PM10 samples were collected during haze episodes in
      Zhengzhou (113 degrees 28' E, 34 degrees 37' N), a highly populated city in North
      China. The samples were used to examine the inorganic ion chemistry of
      particulate matter (PM) of local origin at light (PM2.5 < 60 MUg m-3 and PM10 <
      135 MUg m-3), medium (PM2.5: 60-170 MUg m-3 and PM10: 135-325 MUg m-3), and
      severe (PM2.5 > 170 MUg m-3 and PM10 > 325 MUg m-3) pollution levels. At the
      light and severe pollution levels, the increase of PM10 was accounted for by the
      increase of PM2.5, and the variation of PM10-2.5 was small. In contrast, the
      increase of PM10 at the medium pollution level was caused by the increase in both
      PM2.5 and PM10-2.5. Sulfate (SO42-), nitrate (NO3-), ammonium (NH4+), and
      chloride in the form of ammonium chloride (Cl-S) accounted for 47.8% and 60.3% of
      the PM2.5 mass at the light and severe levels, respectively. These values
      indicate a large contribution of secondary inorganic species to the PM2.5 growth.
      As the pollution level changed from light to medium, the contribution of SO42- to
      the growth of PM2.5 decreased from 49.0% to 15.1%, while those of NO3- and Cl-S
      increased from 25.1% and 0.6% to 32.5% and 2.8%, respectively, indicating the
      substantial production of nitrate and chloride. At the severe level, the
      contribution of SO42- was 30.1%, while those of NO3- and Cl-S were 5.9% and 0.5%,
      respectively, suggesting a hindering effect of sulfate on the production of
      nitrate and chloride. These results indicate that the production of secondary
      species with the increase of PM2.5 was dominated by sulfate-associated
      conversions at the light and severe pollution levels and was substantially
      influenced by nitrate- and chloride-associated conversions at the medium
      pollution level. The estimation of carbonate presence in the PM indicates that
      part of the carbonate in coarse particles (PM10-2.5) of crustal origin enhanced
      sulfate production via heterogeneous surface reactions. Quantification of the
      contribution of primary and secondary species to PM2.5 showed that it was
      dominated by both primary and secondary particles at the light pollution level,
      and it was mainly composed of secondary species at the severe pollution level.

PMID- 30205347
TI  - Comparative analysis between different methods for calculating on-board ship's
      emissions and energy consumption based on operational data.
AB  - With the aim of more reliably measuring ships' fuel consumption and emissions
      several different estimation methods have been put forward and are in use but
      there is ongoing debate still on the best way to measure maritime emissions. Fuel
      and emissions monitoring are already a common practice in the shipping industry.
      But there are currently neither harmonised guidelines nor legal requirements that
      clearly define the method and the rules to follow to monitor on-board fuel
      consumption for each situation during navigation. In this context, this article
      describes and compares four existing methods (EPA, IMO, Jalkanen and MAN) for
      calculating energy consumption and emissions, and presents a more realistic
      method, based on a case study. The purpose is to examine the differences between
      all of these methods, in order to propose the most suitable method of obtaining
      the data needed for better energy management, and a method that can be applied to
      any type of ship. The case study was carried out on Ro-Pax ships, comparing these
      four different methods through the application of a bottom-up integrated system
      approach. The study describes in detail and applies the most complete methodology
      for calculating energy consumption and emissions during cruising, operating in a
      Speed Reduction Zone (SRZ), manoeuvring and berthing. Application of the new
      improved method proposed in this paper could be the first step in implementing
      operational measures for detecting both abnormal high emissions and abnormal fuel
      consumption. The application of this method does not, in itself, reduce fuel use
      or improve efficiency, but it should be the necessary first step to establish
      uniform operational measures that will improve the management of energy on board
      ship and monitor accurately the performance of the fleet.

PMID- 30205348
TI  - Occurrence and bioconcentration of micropollutants in Silver Perch (Bidyanus
      bidyanus) in a reclaimed water reservoir.
AB  - This study examined the occurrence of 49 micropollutants in reclaimed water and
      Silver Perch (Bidyanus bidyanus) living in a reclaimed water reservoir. The
      numbers of micropollutants detected in reclaimed water, Silver Perch liver, and
      Silver Perch flesh were 20, 23, and 19, respectively. Concentrations of all
      micropollutants in reclaimed water, except benzotriazole, were well below the
      Australian Guideline for Recycled Water (AGRW) values for potable purposes. The
      concentration of benzotriazole in reclaimed water was 675 +/- 130 ng/L while the
      AGRW value for this compound was 7 ng/L. Not all micropollutants detected in the
      water phase were identified in the Silver Perch flesh and liver tissues.
      Likewise, not all micropollutants detected in the Silver Perch flesh and liver
      were identified in the reclaimed water. In general, micropollutant concentrations
      in the liver were higher than in the flesh. Perfluorooctane sulfonate (PFOS) was
      detected at a trace level in reclaimed water well below the AGRW guideline value
      for potable purposes, but showed a high and medium bioconcentration factor in
      Silver Perch liver and flesh, respectively. In addition, the risk quotient for
      PFOS was medium and high when considering its concentration in Silver Perch liver
      and flesh, respectively. Results reported here highlight the need to evaluate
      multiple parameters for a comprehensive risk assessment. The results also single
      out PFOS as a notable contaminant of concern for further investigation.

PMID- 30205349
TI  - Phytoextraction potential of Pteris vittata L. co-planted with woody species for
      As, Cd, Pb and Zn in contaminated soil.
AB  - The objective of this study was to determine the phytoextraction potential of a
      hyperaccumulator co-planted with a large biomass of woody plant in metal(loid)
      contaminated soil. A pot experiment was conducted for 270 days (d) to study the
      growth, physiological responses, and metal(loid)s accumulation characteristics of
      plants, which included a shade-requiring, As-hyperaccumulator perennial herb,
      Pteris vittata L., co-planted with a woody tree, namely Morus alba L. or
      Broussonetia papyrifera L., for soil contaminated with arsenic (As), cadmium
      (Cd), lead (Pb), and zinc (Zn). The results showed that the biomass,
      photosynthetic pigment contents, antioxidant enzyme activity, and uptake of As in
      P. vittata L. were significantly enhanced by co-planting with M. alba L. or B.
      papyrifera L. Especially, the uptake of As by P. vittata L. was significantly (p
      < 0.05) increased by 80.0% and 64.2% when it was co-planted with M. alba L. or B.
      papyrifera L., respectively, while the As, Cd, Pb, and Zn contents of both M.
      alba L. and B. papyrifera L. were not significantly promoted by the co-planting.
      The comprehensive phytoextraction of metal(loid)s could be optimized by the co
      planting of P. vittata L. with M. alba L. or B. papyrifera L. The total amount of
      As in the shoots from co-planting species was significantly (p < 0.05) higher
      than that of the monoculture with M. alba L. or B. papyrifera L., and that of Cd
      and Zn in the shoots was significantly (p < 0.05) higher than that of the
      monoculture with P. vittata L. The results showed that the co-planting of P.
      vittata L. with M. alba L. or B. papyrifera L. can alleviate the toxic effects of
      metal(loid)s on plant growth and improve the comprehensive phytoextraction
      amounts of metal(loid)s, and is a promising strategy for remediation of
      metal(loid)-contaminated soil.

PMID- 30205350
TI  - Changes in percentages of perceived met needs for care over time in a Canadian
      longitudinal cohort.
AB  - There is a paucity of research on determinants associated with changes in
      perceived met needs for care over time. This study used a longitudinal cohort to
      explore changes in percentages of perceived met needs over time and to identify
      its related determinants. Data analyzed was from a longitudinal community-based
      survey. A total of 150 participants received at least one type of help both at
      baseline and a 2-year follow-up. Multivariate analyses were used. Perceived met
      needs of the study sample slightly increased over time. People who had a higher
      percentage of met needs at baseline were less likely to have an increase in
      percentage of perceived met needs at the 2-year follow-up, whereas, those who had
      a higher value of wellbeing and an increase in the value of mental wellbeing over
      time, were associated with an increase in the percentage of met needs at the 2
      year follow-up. Determinants associated with changes in percentages of perceived
      met needs could be the target for improving perceived need for mental health
      care. Findings of this study indicate the need for longitudinal studies in
      perceived need for mental health services.

PMID- 30205351
TI  - Testing the exacerbation and attenuation hypotheses of the role of anxiety in the
      relation between ADHD and reactive/proactive aggression: A 10-year longitudinal
      study.
AB  - Both anxiety and aggression commonly co-occur with ADHD symptoms. Two competing
      hypotheses describing the role of anxiety in aggression associated with ADHD
      symptoms have previously been advanced. The exacerbation hypothesis proposes that
      the presence of anxiety increases the risk of aggression in the context of ADHD
      symptoms. The attenuation hypothesis proposes that the presence of anxiety
      protects against aggression in the context of ADHD symptoms. We tested these
      hypotheses using moderated cross-lagged panel models in the Zurich project on
      social development from childhood to adulthood (z-proso) sample using both self
      report (3 waves) and informant-report (8 waves) data spanning ages 7-17. We found
      evidence that anxiety protects against both reactive and proactive aggression;
      however, the effect was direct: there was no evidence for anxiety moderating the
      strength of ADHD symptom-aggression links. Results suggest that anxiety likely
      plays an important role in inhibiting aggression but does not interact with ADHD
      symptoms in the manner predicted by either the exacerbation or attenuation
      hypothesis.

PMID- 30205352
TI  - Drug-induced gambling disorder: A not so rare but underreported condition.
AB  - The widespread use of dopaminergic agents for the treatment of Parkinson's
      disease has revealed the presence of gambling disorder (GD) as an uncommon, but
      serious, adverse reaction to these agents. We describe the main characteristics
      of drug-induced GD reports received by the Spanish Pharmacovigilance System
      during the period from 1983 to 2016. Fifteen reports of GD have been identified.
      Dopaminergic agonists, especially pramipexole, are the main drugs involved in
      inducing GD. Physicians prescribing these drugs should warn patients and families
      about this disorder. Knowledge of this disorder will encourage early diagnosis,
      treatment, and reporting of this clinically and socially relevant disorder.

PMID- 30205353
TI  - Domain-specific associations between disability and depression, anxiety, and
      somatization in primary care patients.
AB  - This study explores the associations between different disability domains and the
      most prevalent symptoms of mental disorders in primary care patients (i.e.
      depression, anxiety, and somatization). A total of 1241 participants from 28
      primary care centres completed self-report measures of depression, anxiety, and
      somatization. This same sample also completed the Sheehan Disability Scale (SDS)
      to assess functional impairment in work, social life, and family life domains.
      Associations between the symptoms and each disability domain were examined using
      hierarchical regression analyses. Depression emerged as the strongest predictor
      of all three disability domains. Somatization was associated only with the work
      domain, and anxiety was associated only with the family life domain. Clinical
      symptoms explained a greater proportion of the variance than sociodemographic
      variables. In primary care patients, depression, anxiety and somatizations were
      associated with distinct domains of disability. Early provision of effective
      treatments in the primary care setting may be crucial to reduce the societal
      burden of common mental disorders.

PMID- 30205354
TI  - EcircPred: Sequence and secondary structural property based computational
      identification of exonic circular RNAs.
AB  - Circular RNAs are new class of stable non-coding RNAs, whose expressions are
      specific to tissues as well as developmental stages and reported to act as gene
      regulators. Conspicuous presences of some of them as biomarkers for cancers,
      aging etc. are well reported. Biogenesis of circular RNA competes with Pre-mRNA
      splicing using the same splicing machinery and gene loci. Also, some circular
      RNAs are reported to have open reading frames and internal ribosome entry site
      for ribosome binding, which increases the chance of overlapping features among
      circular and mRNA transcripts. Therefore, discriminating the Exonic circular RNAs
      and mRNAs solely through sequence properties is challenging. However, possible
      discriminating factors, such as, reports on non-canonical arrangement of exons in
      circular RNAs were cited. This study was dedicated to classify Circular RNAs from
      mRNAs by recruiting features extracted from sequences as well as predicted
      secondary structures and ANN classifier models for all these feature types. The
      features were statistics of di-nucleotide index, emission probability of RNA
      sequences and entropy of di-nucleotides. Finally a simple decision voting was
      applied to combine decisions obtained from multiple classifiers. After performing
      10 fold cross validation we obtained average values of efficiency, sensitivity,
      specificity and Mathews correlation coefficient as 0.8374, 0.8544, 0.8203 and
      0.6753 respectively. In the backdrop of few reports of identification of circular
      RNAs from constitutive exons and other long non-coding RNAs, this is the first
      report of discriminating exonic circular RNAs from mRNAs using sequence and
      sequence-derived properties.

PMID- 30205356
TI  - Erector spinae plane block for acute postoperative pain management after anterior
      thoracolumbar spine surgery.

PMID- 30205355
TI  - Effects of deep tillage and municipal green waste compost amendments on soil
      properties and tree growth in compacted urban soils.
AB  - Large trees are often seen as a means of offsetting negative consequences of
      growing urban densification. To increase the tree canopy cover of dense urban
      landscapes, developers, planners and urban tree managers are often forced to
      plant into damaged and compacted sites. Compacted urban soils can hinder the
      establishment and growth of deep rooted, woody plants by: 1) impeding root
      exploration and development which is critical for water and nutrient acquisition;
      2) reducing infiltration of water into the soil and the availability of water to
      plants; and 3) reducing gas exchange and the balance between anaerobic and
      aerobic conditions. At three sites in Melbourne, Australia with compacted and
      damaged soils, we established four soil remediation treatments: 1 & 2) tillage to
      0.25 m with and without 50% (v/v) municipal green waste compost (MGWC) additions,
      and 3 & 4) tillage to 0.5 m with and without 50% MGWC addition, plus a non
      remediated control. Each treatment was replicated (n = 3), and one Corymbia
      maculata (spotted gum) tree was planted into the centre of each 2 * 2 m treatment
      plot (n = 15), at all three sites (n = 45). Bulk density and field-saturated
      hydraulic conductivity were improved by tillage, at least in the short-term. The
      use of MGWC may maintain these changes for longer. Depending on site soil
      conditions tree growth may be improved by tillage alone. At one site, we found
      that additions of MGWC lead to nitrogen immobilisation due to site soil
      conditions. At another site, deep tillage (with or without MGWC) led to
      significantly improved tree growth. Compacted and degraded urban soils may be
      improved through simple tillage and/or organic amendment strategies for the
      successful establishment of deep rooted woody plants. However, site soil
      conditions will dictate whether the addition of MGWC is beneficial or not, as one
      site showed no positive response to any tillage or MGWC. This research has
      examined a technique that can be used by landscape managers to improve soil
      physical characteristics and, in certain circumstances, can improve deep-rooted
      woody plant establishment and growth in challenging compacted urban soil
      conditions.

PMID- 30205357
TI  - Modulation of the gut microbiota to improve innate resistance.
AB  - One major benefit from the association of hosts with the complex microbial
      communities that establish at body surfaces is the resistance to pathogen
      infection. This protective role of symbiotic microbes is becoming ever more
      relevant, given the alarming rise of multidrug-resistant pathogens and severe
      infections in patients following extensive antibiotic treatment. Herein, we
      highlight some recent mechanistic studies that have provided insights into how
      the highly dynamic dialogue amongst intestinal bacteria and between intestinal
      bacteria and their host can contribute to protect the host against pathogens in
      and outside the gut. We then discuss how delineating the rules of this dialogue
      can help design strategies to modulate the microbiota and improve host resistance
      to infections.

PMID- 30205358
TI  - Amyloid-beta-related and unrelated cortical thinning in dementia with Lewy
      bodies.
AB  - Coexisting Alzheimer's disease (AD) pathology is common in patients with dementia
      with Lewy bodies (DLB). To evaluate the cortical thinning in patients with DLB
      considering the effect of amyloid-beta (Abeta), we compared the regional cortical
      thickness between control subjects and patients with DLB with abnormal dopamine
      transporter imaging. Seventeen (43.6%) of 39 patients with DLB and no control
      subjects had significant Abeta deposition on 18F-florbetaben positron emission
      tomography. Compared to control (n = 15), Abeta-negative DLB group (n = 21) had
      cortical thinning in the bilateral insula, entorhinal, basal frontal, and
      occipito-parietal cortices. Compared to Abeta-negative DLB, Abeta-positive DLB
      group (n = 15) had a lower cortical thickness in the AD-prone brain regions in
      addition to the bilateral occipital, basal frontal, and somatomotor cortices.
      After controlling for the amount of Abeta deposition, DLB group had cortical
      thinning in the same regions affected in the Abeta-negative DLB group. In
      summary, patients with DLB had an Abeta-independent cortical thinning, while
      Abeta was associated with additional cortical thinning in the AD-prone brain
      regions and the aggravation of DLB-specific cortical thinning.

PMID- 30205359
TI  - Resident brain neural precursor cells develop age-dependent loss of therapeutic
      functions in Alzheimer's mice.
AB  - There is vast knowledge on pathogenic mechanisms in Alzheimer's disease but very
      little on means by which the brain protects itself from disease. A major
      candidate in providing neuroprotection is the resident brain neural
      precursor/stem cell (NPC) pool. Transplanted NPCs possess powerful immune
      modulatory and trophic properties in vivo and in vitro, underscoring the question
      whether resident brain NPCs have any role in regulating disease pathology in
      Alzheimer's disease, and particularly whether they fail to protect the brain from
      degeneration. To evaluate brain NPC function in relation to disease pathology, we
      first characterized the pathological properties of 5xFAD transgenic mouse model
      of Alzheimer's disease at different ages. We found that age 7 months is a
      critical time point of heavy amyloid deposition and gliosis but before
      neurodegeneration and a normal basal rate of NPC turnover in the subventricular
      zone (SVZ) of 5xFAD mice as compared to wild-type mice. Analysis of NPC
      functional properties showed that despite preserved rate of turnover, there was
      substantial SVZ NPC dysfunction as indicated by both ex vivo and in vivo assays.
      Freshly isolated NPCs from 7-month-old 5xFAD mice exhibited reduced expansion
      rate and diminished immune-modulatory and trophic properties. Moreover, there was
      slowed recovery of SVZ NPCs after cytosine-arabinoside insult and markedly
      reduced migratory response following a lysolecithin-induced lesion in the corpus
      callosum in vivo. Importantly, these functions were fully preserved in 2-month
      old 5xFAD mice, a time point before Alzheimer's disease-specific pathological
      changes. There was reduced expression of key genes involved in NPC proliferative
      and migratory response in NPCs derived from 7-month-old 5xFAD mice. The
      dysfunctional properties and downregulation of gene expression were reversible in
      NPCs derived from 7-month-old 5xFAD mice following in vitro expansion and were
      reproduced in wild-type NPC by addition of amyloid beta peptide. Thus, there is
      age-dependent acquired NPC dysfunction, with loss of immune-modulatory and
      neurotrophic properties, which is induced by the pathological Alzheimer's brain
      environment at a critical time point before neurodegeneration. We suggest that
      failure of resident NPC to provide tissue support may be involved in promoting
      neurodegeneration.

PMID- 30205360
TI  - In silico models in drug development: where we are.
AB  - The use and utility of computational models in drug development has significantly
      grown in the last decades, fostered by the availability of high throughput
      datasets and new data analysis strategies. These in silico approaches are
      demonstrating their ability to generate reliable predictions as well as new
      knowledge on the mode of action of drugs and the mechanisms underlying their side
      effects, altogether helping to reduce the costs of drug development. The aim of
      this review is to provide a panorama of developments in the field in the last two
      years.

PMID- 30205361
TI  - Direct sunlight enabled photo-biochemical synthesis of silver nanoparticles and
      their Bactericidal Efficacy: Photon energy as key for size and distribution
      control.
AB  - It is highly desirable to discover novel green synthesis methods for cheap and
      scalable synthesis of nanoparticles (NPs) to reduce the negative impact on the
      environment. But these approaches generally impose great challenge in controlling
      size, shape, and homogeneity of product NPs. Here in the present study, we report
      a novel approach enabling direct sunlight and oyster mushroom (Pleurotus
      citrinopileatus) extract for the photo-biochemical synthesis of Ag NPs. Sunlight
      of different wavelength was used to control the size and distribution of photo
      biochemically produced NPs. Interestingly, it is observed that a smaller
      wavelength of sunlight produces smaller sized of NPs with a narrow size
      distribution. For examples; blue sunlight produces colloidal silver NPs with an
      average diameter of ~ 3.28 nm and 0.72 nm size distribution, while full sunlight
      produces comparatively larger sized (7.08 nm) NPs with wider (2.92 nm) size
      distribution. Since present approach uses only direct sunlight, freely available
      renewable energy source, a cheap biological extract as reducing and capping agent
      and cheap silver precursor, therefore it is an environment-friendly approach and
      can be used for the synthesis of NPs at industrial scale. Moreover, the size
      dependent bactericidal effect has also been studied against pathogenic,
      Escherichia coli, bacteria. The minimum inhibitory concentration (MIC) 25 ppm and
      MBC 30 ppm have been observed for silver NPs of 3.28 nm average diameter.

PMID- 30205362
TI  - Antiplatelet therapy for elderly patients with Acute Coronary Syndromes.

PMID- 30205364
TI  - Inner Ear Damage by Firecracker Trauma.
AB  - Firecrackers are still popular among the general public of various populations
      worldwide. This study investigated inner ear damage in patients with firecracker
      trauma and analyzed noise levels in 6 kinds of commercially available
      firecrackers. During the past 20 years, we have experienced 30 patients with
      firecracker trauma. An inner ear test battery comprising audiometry, cervical and
      ocular vestibular-evoked myogenic potential (cVEMP and oVEMP) tests and a caloric
      test was performed. The real-time noise levels were measured outdoors at a
      distance of 2, 4 and 6 m away from a lighting firecracker to mimic a noise event.
      Mean hearing levels at high frequencies (4,000 and 8,000 Hz) were significantly
      higher than those at the low and middle frequencies, indicating that firecrackers
      mostly cause high-tone hearing loss. For the vestibular damage, abnormality
      percentages were higher in the results of cVEMP (80%) and oVEMP (60%) tests, but
      not in the caloric test (8%). In conclusion, most firecrackers exhibited noise
      levels > 110 dB SPL even at a distance of 6 m. This blast injury simultaneously
      damaged the cochlea, saccule and utricle, but spared the semicircular canals,
      indicating that blast exposure potentiates the adverse effect of noise exposure
      on both cochlear and vestibular partitions.

PMID- 30205363
TI  - A seven-long noncoding RNA signature predicts overall survival for patients with
      early stage non-small cell lung cancer.
AB  - Non-small cell lung cancer (NSCLC) is the most common cancer and cause of cancer
      related mortality globally. Increasing evidence suggested that the long non
      coding RNAs (lncRNAs) were involved in cancer-related death. To explore the
      possible prognostic lncRNA biomarkers for NSCLC patients, in the present study,
      we conducted a comprehensive lncRNA profiling analysis based on 1902 patients
      from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets.
      In the discovery phase, we employed 682 patients from the combination of four GEO
      datasets (GSE30219, GSE31546, GSE33745 and GSE50081) and conducted a seven-lncRNA
      formula to predict overall survival (OS). Next, we validated our risk-score
      formula in two independent datasets, TCGA (n=994) and GSE31210 (n=226).
      Stratified analysis revealed that the seven-lncRNA signature was significantly
      associated with OS in stage I patients from both discovery and validation groups
      (all P<0.001). Additionally, the prognostic value of the seven-lncRNA signature
      was also found to be favorable in patients carrying wild-type KRAS or EGFR.
      Bioinformatical analysis suggested that the seven-lncRNA signature affected
      patients' prognosis by influencing cell cycle-related pathways. In summary, our
      findings revealed a seven-lncRNA signature that predicted OS of NSCLC patients,
      especially in those with early tumor stage and carrying wild-type KRAS or EGFR.

PMID- 30205365
TI  - Medical Procedure-Related Transient Global Amnesia.
AB  - BACKGROUND: Transient global amnesia (TGA) is an interesting clinical syndrome
      characterized by sudden memory loss for recent events and an inability to retain
      new memories usually lasting several hours and recovering spontaneously. We
      conducted a literature search of medical procedure-related TGA and its
      predisposing conditions. METHODS: We performed PubMed searches using the keyword
      "transient global amnesia" combined with "procedure," "test," "therapy," or
      various other individual medical procedures. In addition, we described 2 cases of
      gastroscopy-related TGA. RESULTS: Eighty-nine patients with medical procedure
      related TGA in 49 articles were summarized. The most common procedure was
      cerebral angiography (n = 45), followed by coronary angiography (n = 10) and
      general anesthesia (n = 9). After categorization, neurological procedures were
      most common (n = 46, 51.7%), followed by cardiac (n = 17, 19.1%), anesthetic (n =
      11, 12.4%), gastrointestinal (n = 4, 4.5%), and pulmonary (n = 2, 2.2%)
      procedures. CONCLUSIONS: Diverse cases of medical procedure-related TGA have been
      reported in the literature. Valsalva-associated activities, emotional stress with
      anxiety, and acute pain were predisposing conditions. An understanding of medical
      procedure-related TGA may be important for clinicians who perform such medical
      procedures.

PMID- 30205367
TI  - Conservative Treatment versus Surgery for Laryngeal Contact Granuloma: A
      Prospective Study.
AB  - AIMS: To confirm the efficacy of conservative treatment for laryngeal contact
      granuloma and identify factors influencing treatment outcome. METHODS: In this
      prospective study, patients with laryngeal contact granuloma were divided into a
      group receiving conservative treatment and a group undergoing surgery. Efficacy
      was assessed by analyzing the complete response after a 48-week follow-up. The
      association of treatment outcome with clinical factors was then evaluated.
      RESULTS: In total, 61 patients, 43 in the group receiving conservative treatment
      and 18 in the group undergoing surgery, were analyzed, and the complete response
      rate was 72.1% and 38.9%, respectively. Both univariate analysis and multivariate
      analysis revealed that treatment modality (p1 = 0.015, p2 = 0.043), voice abuse
      (p1 = 0.010, p2 = 0.010), and the size of the granuloma (p1 = 0.031, p2 = 0.020)
      were significantly associated with the complete response of laryngeal contact
      granuloma. Kaplan-Meier curves showed that alcohol consumption (p = 0.031), voice
      abuse (p < 0.001), and granuloma size (p = 0.025) were significantly related to
      the complete response of conservative treatment. CONCLUSIONS: This prospective
      study strengthens the argument for conservative treatment (instead of surgery) as
      the first choice for laryngeal contact granuloma. The results also suggest that
      voice abuse, alcohol consumption, and the size of the granuloma may predict
      treatment outcome.

PMID- 30205366
TI  - Association Between the Deletion Allele of Ins/Del Polymorphism (Rs145204276) in
      the Promoter Region of GAS5 with the Risk of Atherosclerosis.
AB  - BACKGROUND/AIMS: LncRNA is a growth arrest-specific transcript 5 (GAS5) with
      tumor suppressor activities in some cancers, but its role in atherosclerosis is
      unclear. METHODS: Bioinformatics algorithm analysis was utilized to search the
      target of GAS5 and miR-21, followed by luciferase assay to confirm these targets.
      Real-time PCR and western-blot were utilized to verify the connection among GAS5,
      miR-21 and Programmed cell death 4 (PDCD4). MTT assay and flow cytometry analysis
      were performed to explore the mechanism of GAS5 in the regulation of
      atherosclerosis. RESULTS: GAS5 directly targets miR-21 and functions as a
      competing endogenous RNA to suppress miR-21 expression. We also observed that
      rs145204276 polymorphism, including INS/INS and DEL/DEL, on GAS5 promoter
      increased transcription activity of GAS5, but the presence of rs145204276 DEL/DEL
      allele significantly promoted the transcription of GAS5 promoter compared with
      rs145204276 INS/INS allele. PDCD4 was predicted as a direct target gene of miR-21
      with a binding site on PDCD4 3'UTR. It was further confirmed by luciferase assay
      that miR-21 significantly reduced the luciferase activity of wild-type PDCD4
      3'UTR but not that of mutant PDCD4 3'UTR. In addition, high glucose significantly
      inhibited the growth rate of EC genotyped as DEL/DEL or INS/ INS, and apparently
      promoted the apoptotic rate of either DEL/DEL or INS/INS genotype ECs.
      Furthermore, the effect of high glucose was stronger in the INS/INS group, while
      the expression of GAS5 was dramatically upregulated with the presence of GAS5
      DEL/DEL, while GAS5 positively regulated PDCD4 expression via inhibiting miR-21
      expression. GAS5 siRNA and miR-21 mimics significantly decreased GAS5 and PDCD4
      expressions, and the inhibitory effects of GAS5 siRNA or miR-21 mimics on GAS5
      and PDCD4 expressions in the INS/INS group was stronger. Moreover, GAS5 siRNA and
      miR-21 mimics remarkably triggered cells proliferation and suppressed cell
      apoptosis, and the inhibition effects of GAS5 siRNA or miR-21 mimics on either
      cell viability and apoptosis in the INS/INS group was stronger. In this study, we
      enrolled 1,306 subjects with or without atherosclerosis and found that the
      INS/DEL or DEL/DEL genotypes significantly decreased the risk of atherosclerosis
      compared with the ins/ins genotype (adjusted odds ratio: 0.74 and 0.40,
      respectively). CONCLUSION: In summary, rs145204276 was associated with the risk
      of atherosclerosis by affecting the proliferation and apoptosis of endothelial
      cells via regulating the GAS5/miR-21/PDCD4 signaling pathway.

PMID- 30205368
TI  - Kisspeptin/GPR54 System: What Do We Know About Its Role in Human Reproduction?
AB  - Kisspeptin is involved in the control of human reproduction bridging the gap
      between the sex steroid levels and feedback mechanisms that control the
      gonadotropin releasing hormone (GnRH) secretion; however, studies considering
      this peptide and infertility are limited. We conducted a review and critical
      assessment of available evidence considering kisspeptin structure, physiology,
      function in puberty and reproduction, its role in assisted reproduction
      treatments, kisspeptin dosage and the impact on KISS1 and GPR54 genes. Literature
      searches were conducted in PubMed using keywords related to: (i) kisspeptin or
      receptors, kisspeptin-1 (ii) reproduction or infertility or fertility (iii) gene
      and (iv) dosage or measurement or quantification or serum level, in human.
      Kisspeptin is a product of KISS1 gene that binds to a G-protein-coupled receptor
      (GPR54/KISS1R) stimulating the release of GnRH by hypothalamic neurons, leading
      to secretion of pituitary gonadotropins (LH and FSH) and sexual steroids, which
      in turn will act in the gonads to produce the gametes. Kisspeptin is being
      recognized as a crucial regulator of the onset of puberty, the regulation of sex
      hormone mediated secretion of gonadotropins, and the control of fertility.
      Inactivating and activating mutations in both KISS1 or GPR54 genes were
      associated with hypogonadotropic hypogonadism and precocious puberty. Despite
      this, studies considering kisspeptin and infertility are scarce. The
      understanding of the role of kisspeptin may lead to its use as a biomarker in
      infertility treatments and use in controlled ovarian hyperstimulation.

PMID- 30205369
TI  - The Pituitary Gland is a Novel Major Site of Action of Metformin in Non-Human
      Primates: a Potential Path to Expand and Integrate Its Metabolic Actions.
AB  - BACKGROUND/AIMS: Biguanides are anti-hyperglycaemic agents used to treat diabetes
      by acting primarily on the liver, inhibiting hepatic gluconeogenesis. However,
      biguanides may target other key metabolic tissues to exert beneficial actions. As
      the "master endocrine gland", the pituitary is a true homeostatic sensor that
      controls whole body homeostasis and metabolism by integrating central and
      peripheral signals. However, whether the pituitary is a primary site of
      biguanides action in normal adult humans/primates remains unknown. Therefore, we
      aimed to elucidate the direct effects of two biguanides (metformin/phenformin) on
      the expression and secretion of all anterior pituitary hormones in two non-human
      primate species (Papio anubis and Macaca fascicularis), and the
      molecular/signalling-mechanisms behind these actions. METHODS: Primary pituitary
      cell cultures from baboons and macaques were used to determine the direct impact
      of metformin/phenformin (alone and combined with primary regulators) on the
      functioning of all pituitary cell-types (i.e. expression/secretion/signaling
      pathways, etc). RESULTS: Metformin/phenformin inhibited basal, but not
      GHRH/ghrelin-stimulated GH/ACTH/ FSH-secretion and GH/POMC-expression, without
      altering secretion or expression of other pituitary hormones (PRL/LH/TSH), FSH
      expression or cell viability in both primate models. These biguanide actions are
      likely mediated through modulation of: 1) common (mTOR/PI3K/intracellular
      Ca2+mobilization) and distinct (MAPK) signaling pathways; and 2) gene expression
      of key receptors regulating somatotrope/corticotrope/gonadotrope function (i.e.
      upregulation of SSTR2/SSTR5/INSR/IGF1R/LEPR). CONCLUSION: The pituitary gland is
      a primary target of biguanide actions wherein they modulate
      somatotrope/corticotrope/gonadotrope-function through multiple
      molecular/signaling pathways in non-human primate-models. This suggests that the
      well-known metabolic effects of biguanides might be, at least in part, influenced
      by their actions at the pituitary level.

PMID- 30205370
TI  - miR-26a/HOXC9 Dysregulation Promotes Metastasis and Stem Cell-Like Phenotype of
      Gastric Cancer.
AB  - BACKGROUND/AIMS: Previous studies demonstrated that HOXC9 acts as an oncogene in
      several tumors. The aim of this study was to explore whether HOXC9 promotes
      gastric cancer (GC) progression and elucidate the underlying molecular
      mechanisms. METHODS: HOXC9 expression in GC tissues and adjacent non-cancer
      tissues was detected by quantitative RT-PCR (qRT-PCR) and immunohistochemistry.
      The functional effects of HOXC9 on proliferation, metastasis and stem cell-like
      phenotype were evaluated by relevant experiments in GC cells. The effect of miR
      26a on HOXC9 was investigated by gain- and loss-of-function assays and luciferase
      reporter assay. Nude mouse models were established to test the effect of miR-26a
      and HOXC9 on tumorigenesis and metastasis of GC cells in vivo. RESULTS: Herein,
      we showed that HOXC9 was upregulated in GC tissues and associated with a poor
      prognosis. HOXC9 knockdown inhibited the metastasis and stem cell-like phenotype
      of GC cells without significant effects on cell proliferation. In addition, we
      identifed HOXC9 as a direct target of miR-26a. Restoration of miR-26a in GC cells
      downregulated HOXC9 and reversed its promoting effect on metastasis and self
      renewal, whereas miR-26a silencing upregulated HOXC9. In vivo experiments showed
      that HOXC9 knockdown suppressed tumorigenesis and lung metastasis of GC cells in
      nude mice, and these effects were mimicked by restoration of miR-26a. CONCLUSION:
      The present study demonstrates that HOXC9 promotes the metastasis and stem cell
      like phenotype of GC cells, and this phenomenon can be reversed by restoration of
      miR-26a.

PMID- 30205372
TI  - Prevalence of Phototherapy in the Age of Biologics.
AB  - BACKGROUND: The prevalence of narrow-band ultraviolet B (NB-UVB) use in Europe
      for moderate and severe psoriasis is unknown, because national registries for
      psoriasis do not monitor this treatment. OBJECTIVES: To quantify the use of
      phototherapy, biologics or conventional treatments in psoriasis, in a setting
      where European Medicines Agency (EMA) eligibility criteria for biologics were
      strictly applied, and phototherapy was included among first-line treatments.
      METHODS: We followed a cohort of 1,090 patients who were referred to the only
      centre entitled to prescribe biologics and phototherapy during a 5-year period.
      RESULTS: The cumulative number of treatment cycles was: 1,047 with NB-UVB
      phototherapy, 650 with systemic treatments and 239 with biologics; 754 patients
      received at least 1 course of NB-UVB phototherapy, 422 at least 1 course with a
      systemic treatment and 137 with a biologic; 595 patients were treated only with
      phototherapy. CONCLUSIONS: Regular use of NB-UVB as first-line treatment for
      moderate and severe psoriasis and adherence to the EMA eligibility criteria for
      biologics led to a relatively restricted use of biologics.

PMID- 30205373
TI  - Open Spina Bifida: Why Not Fetal Surgery?
AB  - OBJECTIVE: The majority of patients counseled for prenatal open spina bifida
      repair (SBR) do not undergo fetal surgery. The aim of this study was to analyze
      the reasons for this phenomenon. MATERIALS AND METHODS: The data of the first 160
      patients seeking counseling or referred to the Zurich Center for Fetal Diagnosis
      and Therapy for prenatal SBR between December 2010 and March 2017 were
      retrospectively analyzed. RESULTS: A total of 104 (65%) patients did not undergo
      prenatal SBR. Of this subgroup, 52% met the exclusion criteria, 35% decided to
      terminate pregnancy, 4% chose to continue pregnancy without fetal intervention,
      and 3% sought care in other European centers. In 6%, data about the ensuing
      course of pregnancy were not recorded. The main exclusion criteria were delayed
      presentation (30%), absence of hindbrain herniation (28%), and concomitant spinal
      anomalies (17%). CONCLUSION: The high percentage of patients not qualifying for
      prenatal SBR underscores the necessity of a standard evaluation of every single
      patient at a qualified referral center. To allow a higher proportion of women
      carrying a fetus with open spina bifida to be timely and correctly informed about
      a potential fetal intervention, much more effort is mandatory to spawn correct,
      objective, and understandable information among all groups of people potentially
      exposed to this topic.

PMID- 30205371
TI  - Effects of Post-Surgical Parenteral Nutrition on Patients with Gastric Cancer.
AB  - BACKGROUND/AIMS: In this study, we investigated the effect of post-surgical
      parenteral nutrition on patients with gastric cancer (GC) and its possible
      mechanism. METHODS: A total of 108 patients were invited to assess for
      eligibility and 28 patients were excluded. The eighty patients were randomized to
      either a study group (1 L peripheral intravenous nutrition, 700 kcal) or a
      control group (1 L isotonic electrolyte solution). Parenteral nutrition was
      started on day 1 post-surgery and maintained for 4-8 days. Levels of albumin
      (ALB), prealbumin (PAB), hemoglobin (Hb) were measured before and after
      treatment. Self-rating Scale of Life Quality (SSLQ) and Quality of life (QoL) was
      assessed to analyze the patients' quality of life. Psychological status was
      evaluated using both the Hospital Anxiety and Depression Scale (HADS-A/D) and the
      Patient Health Questionnaire-9 (PHQ-9). Immune function was evaluated by flow
      cytometric analysis of the levels of CD3+, CD4+, and CD8+ cells. RESULTS:
      Following post-surgical parenteral nutrition, the levels of ALB, PAB and Hb were
      significantly higher in the study group than those in the control group. QoL and
      SSLQ scores were also significantly increased, while HAD-A/D and PHQ-9 scores
      were significantly reduced. Furthermore, the percentages of CD3+ and CD4+ cells,
      but not CD8+ cells, as well as the CD4+/CD8+ ratio were significantly increased
      in the study group. There were no significant differences in these parameters
      between the control and study group prior to surgery. CONCLUSION: The results
      suggest that post-surgical parenteral nutrition can significantly improve the
      nutritional and psychological status, QoL, and immune function of patients
      treated surgically for GC.

PMID- 30205375
TI  - Is a Surgical Approach Justified in Metachronous Krukenberg Tumor from Gastric
      Cancer? A Systematic Review.
AB  - BACKGROUND: The treatment of metachronous Krukenberg tumor (mKT) from gastric
      cancer remains unexplored. We performed a literature review to evaluate whether
      or not surgical treatment improves survival. METHODS: A systematic review
      according to PRISMA guidelines was performed. Studies reporting on patients who
      underwent surgical treatment for mKT from gastric cancer were selected.
      Metachronous disease was divided as follows: confined to the ovaries, confined to
      the pelvis, or beyond the pelvis. Outcomes evaluated included overall survival
      (OS), progression-free survival (PFS), resection rate (R0), and factors
      predicting survival. RESULTS: 13 retrospective reports fulfilled the selection
      criteria (512 patients). Most of the patients presented at a premenopausal age.
      The median presentation interval from gastrectomy ranged from 16 to 21.4 months.
      Median OS ranged between 9 and 36 months. 1-year OS ranged between 52.5 and 59%,
      and 3-years OS between 9.8 and 36.5%. Resection margin, peritoneal seeding, and
      chemotherapy regimen and cycles influenced survival. CONCLUSION: Surgical
      treatment and adjuvant chemotherapy in patients with mKT from gastric cancer
      seems to be associated with improved survival and is justified especially in
      young patients. Disease location and R0 resection should be considered when
      selecting patients.

PMID- 30205374
TI  - Clues to the Pathophysiology of Sudden Cardiac Death in Obstructive Sleep Apnea.
AB  - BACKGROUND: Risk assessment of sudden cardiac death (SCD) is multifactorial and
      complex, especially among individuals without established cardiovascular disease.
      There are insufficiently investigated conditions that can affect
      arrhythmogenesis. One such condition is obstructive sleep apnea (OSA) syndrome,
      which is not on the list of risk factors of the Russian National Society of
      Arrhythmology. OBJECTIVE: The aim of this review article is to discuss clues to
      the pathophysiology of SCD in OSA subjects. METHODS: We searched the literature
      for data reporting the impact of apnea on arrhythmogenesis. The preferred
      languages were English and Russian. The most important clinical reports, as well
      as biochemistry and pathophysiology guides, were selected for inclusion in the
      review. RESULTS: It was clearly observed in the searched literature that OSA is
      the crucial aspect of arrhythmogenesis. Among the clues are intermittent
      nocturnal hypoxia, reactive oxygen species, cardiomyocyte metabolism
      disturbances, myocardial electric heterogeneity, and intrathoracic pressure
      changes. CONCLUSION: This review emphasizes the importance of the inclusion of
      OSA in the list of risk factors of the Russian National Society of Arrhythmology.

PMID- 30205376
TI  - Artemisinin-Daumone Hybrid Inhibits Cancer Cell-Mediated Osteolysis by Targeting
      Cancer Cells and Osteoclasts.
AB  - BACKGROUND/AIMS: Bone metastasis of cancer cells decreases patient survival and
      quality of life. Hybridization via the covalent coupling of two bioactive natural
      products is a useful strategy for developing more potent anticancer agents by
      enhancing their bioavailability and avoiding drug resistance. METHODS: The in
      vivo activities of artemisinin-daumone hybrid 15 (ARTD) were estimated in cancer
      cell-inoculated mice and ovariectomized mice. The viability, migration, and
      invasion of cancer cells were measured via MTT, wound-healing, and transwell
      invasion assays. ARTD-regulated transcription factors were detected with an RT2
      profiler PCR array kit and Western blotting. Osteoclastogenesis and osteoclast
      activity were detected with tartrate-resistant acid phosphatase staining, a pit
      formation assay, gelatin zymography, and a cathepsin K ELISA assay. RESULTS: ARTD
      blocked cancer-associated osteolysis more potently than artemisinin in mice with
      intratibially inoculated breast cancer or lung cancer cells. ARTD inhibited the
      viability, migration, and invasion of breast and lung cancer cells in the absence
      or presence of transforming growth factor-beta1. ARTD treatment induced the
      expression of tumor suppressive activating transcription factor 3 and inhibited
      oncogenic E2F transcription factor 1 expression at the mRNA and protein levels.
      ARTD inhibited receptor activator of nuclear factor kappa-B ligand-induced
      osteoclast formation and bone resorbing activity by reducing the secreted levels
      of matrix metalloproteinase-9 and cathepsin K. Furthermore, ARTD prevented
      estrogen deficiency-induced bone loss in ovariectomized mice. CONCLUSION: ARTD
      may be a promising candidate for inhibiting cancer-induced bone destruction. The
      application of ARTD may be extended to patients with chemotherapy-induced ovarian
      failure or postmenopausal osteoporosis.

PMID- 30205377
TI  - Silence of lncRNA UCA1 Represses the Growth and Tube Formation of Human
      Microvascular Endothelial Cells Through miR-195.
AB  - BACKGROUND/AIMS: Recent studies have suggested that several lncRNAs contribute to
      the angiogenic function of endothelial cells. Herein, we set out to reveal
      whether lncRNA UCA1 has functions in endothelial angiogenesis. METHODS: The
      expression levels of lncRNA UCA1, miR-195 and CCND1 in human microvascular
      endothelial HMEC-1 cells were altered by transfection. Subsequently, cell
      viability, migration, tube formation and apoptosis of HMEC-1 cells were
      respectively assessed. The cross-talk between lncRNA UCA1, miR-195, CCND1, and
      MEK/ERK and mTOR signaling pathways were investigated by performing qRT-PCR and
      Western blotting. RESULTS: Silence of lncRNA UCA1 repressed HMEC-1 cells
      viability, migration, tube formation, and induced apoptosis. Meanwhile, silence
      of lncRNA UCA1 significantly up-regulated miR-195 expression. These alterations
      induced by lncRNA UCA1 were further enhanced by miR-195 overexpression, while
      were attenuated by miR-195 suppression. Moreover, silence of lncRNA UCA1
      deactivated MEK/ERK and mTOR signaling pathways via a miR-195-dependent
      regulation. And the deactivation of MEK/ERK and mTOR signaling pathways led to a
      down-regulation of CCND1. CONCLUSION: This study demonstrates that silence of
      lncRNA UCA1 largely represses microvascular endothelial cells growth and tube
      formation. Silence of lncRNA UCA1 exerts its function possibly via up-regulation
      of miR-195, which in turn inactivates MEK/ERK and mTOR signaling pathways, and
      ultimately represses CCND1 expression.

PMID- 30205378
TI  - Are mTOR and Endoplasmic Reticulum Stress Pathway Genes Associated with Oral and
      Bone Diseases?
AB  - The purpose of this cohort study was to identify associations between combined
      oral and bone disease phenotypes and genes present in cell regulatory pathways.
      The studied pathways play important roles in cellular growth, proliferation,
      differentiation, and homeostasis. DNA samples extracted from whole saliva of
      3,912 individuals were genotyped and these data analyzed according to dental
      caries experience, periapical lesions, periodontitis, osteoporosis, or
      temporomandibular joint discomfort. Samples were obtained from the Dental
      Registry and DNA Repository project at the University of Pittsburgh. Twenty-seven
      polymorphisms in eight genes related to mTOR or endoplasmic reticulum stress
      pathways were selected for genotyping. Allele frequencies and Hardy-Weinberg
      equilibrium were calculated. Analyses were performed comparing genotypes between
      affected and unaffected individuals for each phenotype, as well as for the
      associated phenotypes combined. For all analyses, we used the software PLINK with
      an alpha of 0.002. Borderline associations with multiple variants of several
      genes were found, suggesting that both pathways may be involved in the
      susceptibility to multiple conditions affecting the oral cavity and bones. When
      combining patients that had concomitant dental caries, periodontitis, and
      periapical pathology, several markers in RHEB showed statistically significant
      association. Multiple conditions affecting bone and teeth (i.e., dental caries,
      periodontitis, periapical lesion formation, and osteoporosis) appear to share
      similar underlying genetic etiological factors, which allow us to hypothesize
      that instead of individually, they should be studied in conjunction in human
      populations.

PMID- 30205379
TI  - The Phosphodiesterase Inhibitor Pentoxifylline as a Novel Adjunct to
      Antidepressants in Major Depressive Disorder Patients: A Proof-of-Concept,
      Randomized, Double-Blind, Placebo-Controlled Trial.
AB  - BACKGROUND: There is evidence for an association between major depressive
      disorder (MDD) and both inflammatory and phosphodiesterase (PDE) pathways. This
      study aimed to evaluate the adjunct role of the PDE inhibitor pentoxifylline
      (PTX), a compound with anti-inflammatory properties, in the treatment of adult
      patients with MDD. METHODS: This was a prospective, 12-week, double-blind study
      of parallel groups. Eighty adult outpatients who met the DSM-IV criteria for MDD
      participated in the trial. Patients were required to have a baseline Hamilton
      Rating Scale for Depression (HAM-D) score of at least 18. Patients were allocated
      randomly: 40 received escitalopram 20 mg/day plus placebo while the other 40
      received escitalopram 20 mg/day plus PTX (400 mg b.i.d.). Patients were assessed
      by a psychiatrist at baseline, and 4, 8, and 12 weeks after the medication had
      been started. The serum levels of TNF-alpha, IL-6, IL-10, BDNF, 8-OHdG, and
      serotonin were measured at baseline and after therapy. RESULTS: After 8 and 12
      weeks, the PTX group showed a statistically significantly greater improvement in
      HAM-D score compared to the control group (least squares mean difference [LSMD] 
      3.29, p = 0.000 and LSMD -3.49, p = 0.000, respectively). Moreover, the PTX group
      showed a statistically significantly greater reduction in the serum levels of TNF
      alpha, IL-6, IL-10, and 8-OHdG along with a statistically significant increase in
      the levels of BDNF and serotonin in comparison with the control group after the
      treatment. CONCLUSION: The findings of this study suggest that PTX could be a
      promising adjunct to antidepressants in the treatment of MDD patients.

PMID- 30205380
TI  - Three-Year Hospitalization and Mortality in Elderly Smokers with Chronic
      Obstructive Pulmonary Disease or Chronic Heart Failure.
AB  - BACKGROUND: In elderly smokers, chronic obstructive pulmonary disease (COPD) and
      chronic heart failure (CHF) usually present with dyspnoea. COPD and CHF are
      associated -almost invariably with concomitant chronic diseases, which contribute
      to severity and prognosis. OBJECTIVES: We investigated similarities and
      differences in the clinical presentation, concomitant chronic diseases and risk
      factors for -mortality and hospitalization at 3-year follow-up in elderly
      smokers/ex-smokers with a primary diagnosis of COPD or CHF recruited and followed
      in specialized centers. METHODS: We examined 144 patients with COPD and 96 with
      CHF, >=65 years, >=20 pack/years, and measured COPD Assessment Test (CAT) score,
      modified Medical Research Council, NYHA, and Charlson Index, routine blood test,
      estimated glomerular filtration rate, HRCT scan, 6-min walk test. In addition, in
      each patient we actively searched for CHF, COPD, peripheral vascular disease, and
      metabolic syndrome. RESULTS: COPD and CHF patients had mild to moderate disease,
      but the majority was symptomatic. Comorbidities were highly prevalent and often
      unrecognized in both groups. COPD and CHF patients had a similar risk of
      hospitalization and death at 3 years. Lower glomerular filtration rate, shorter
      6MWT, and ascending aorta calcification score >=2 were independent predictors of
      mortality in COPD, whereas previous 12 months hospitalizations, renal disease,
      and heart diameter were in CHF patients. Lower glomerular filtration rate value,
      higher CAT score, and lower FEV1/FVC ratio were associated with hospitalization
      in COPD, while age, lower FEV1% predicted, and peripheral vascular disease were
      in CHF. CONCLUSIONS: There are relevant similarities and differences between
      patients with COPD and CHF even when admitted to specialized outpatient centers,
      suggesting that these patients should be manage in multidisciplinary units.

PMID- 30205381
TI  - Berberine Exerts a Protective Effect on Gut-Vascular Barrier via the Modulation
      of the Wnt/Beta-Catenin Signaling Pathway During Sepsis.
AB  - BACKGROUND/AIMS: The gut-vascular barrier (GVB) has recently been depicted to
      dampen the bacterial invasion of the bloodstream. The intestinal mucosa is a
      tissue rich in small vessels including capillaries. In this study, the protective
      effect of berberine on GVB in small bowel mucosa was investigated. METHODS: The
      rat cecal ligation and puncture (CLP) sepsis model was employed to evaluate the
      effect of berberine on serum endotoxin level and intestinal vascular permeability
      to Evans blue in vivo. The rat intestinal microvascular endothelial cells
      (RIMECs) treated by lipopolysaccharide (LPS) were used to assess the effect of
      berberine on endothelial permeability to FITC-labeled dextran, transendothelial
      electrical resistance (TEER), and tight junction (TJ) and adherens junction (AJ)
      expression in vitro. RESULTS: After 24-hr CLP operation the serum endotoxin
      concentration and gut vascular permeability were significantly increased, while
      berberine markedly reduced endotoxin level and vascular leakage. In vitro, LPS
      not only dramatically increased endothelial permeability of RIMECs to FITC
      dextran, but also decreased TEER and inhibited claudin-12, beta-catenin and VE
      cadherin expression. These effects of LPS were antagonized by berberine. In
      addition, our in vivo and vitro studies also confirmed that the effect of
      berberine on GVB could be partially abolished by ICG001. CONCLUSION: Berberine
      exerted a protective effect on GVB function in sepsis, which was strictly related
      to the modulation of the Wnt/beta-catenin signaling pathway.

PMID- 30205382
TI  - Identification of O-GlcNAcylation Modification in Diabetic Retinopathy and
      Crosstalk with Phosphorylation of STAT3 in Retina Vascular Endothelium Cells.
AB  - BACKGROUND/AIMS: Recently, we observed an increase in O-GlcNAc (O-linked-beta-N
      acetylglucosamine) modification, and signal transducer and activator of
      transcription proteins 3 (STAT3) expression in primary retinal vascular
      endothelial cells (RVECs) under high glucose conditions and tissues altered by
      diabetic retinopathy (DR). In this study, we focused on the correlations between
      O-GlcNAcylation and STAT3 phosphorylation, and their potential effects with
      regards to DR. METHODS: Expression of O-GlcNAcylation and STAT3 were detected in
      DR-affected tissues and primary RVECs. The relationship between O-GlcNAcylation
      and STAT3 was further delineated by immunoprecipitation and Western blot
      analysis. Effects of O-GlcNAcylation on human RVEC apoptosis and involved protein
      expression were assayed with flow cytometry and Western blot. RESULTS: Global O
      GlcNAcylation and pSTAT3 levels were significantly elevated in diabetic rat
      retina and primary RVECs under high glucose conditions. In vitro assays
      demonstrated that the Tyr705 site was sensitive to high glucose. While O
      GlcNAcylation inhibited p727STAT3 expression, augmented O-GlcNAcylation could
      balance p705STAT3 expression within relatively high levels corresponding to
      vascular endothelial growth factor (VEGF) changes. Immunoprecipitation revealed
      that STAT3 was modified by O-GlcNAcylation and phosphorylation simultaneously.
      Next, we observed that overexpression of O-GlcNAcylation could relieve human RVEC
      apoptosis related to the JAK2-Tyr705STAT3-VEGF pathway. CONCLUSION: O
      GlcNAcylation could relieve RVECs apoptosis through the STAT3 pathway in DR, and
      O-GlcNAcylation combined with STAT3 phosphorylation might open up new insights
      into the mechanisms of DR and other diabetic complications.

PMID- 30205383
TI  - LncRNA HOTAIR Regulates CCND1 and CCND2 Expression by Sponging miR-206 in Ovarian
      Cancer.
AB  - BACKGROUND/AIMS: The long noncoding RNA homeobox (HOX) transcript antisense
      intergenic RNA (HOTAIR) has been demonstrated to be a vital modulator in the
      proliferation and metastasis of ovarian cancer cells, but its potential molecular
      mechanism remains to be elucidated. In the current study, we aimed to uncover the
      biological role of lncRNA HOTAIR and its underlying regulatory mechanism in the
      progression and metastasis of ovarian cancer. METHODS: HOTAIR expression was
      detected by quantitative RT-PCR (qRT-PCR) and northern blotting. The SKOV3
      ovarian cancer cell line was chosen for the subsequent assays. In addition, the
      molecular mRNA and protein expression levels were examined by qRT-PCR and western
      blotting. The competitive endogenous RNA (ceRNA) mechanism was validated by
      bioinformatics analysis and a dual luciferase reporter gene assay. RESULTS:
      HOTAIR expression was significantly higher in ovarian carcinoma tissues and cell
      lines than in the control counterparts. Both CCND1 and CCND2 were downstream
      targets of miR-206. The inhibition of HOTAIR elevated the expression of miR-206
      and inhibited the expression of CCND1 and CCND2. Moreover, CCND1 and CCND2 were
      highly expressed in ovarian cancer tissues, and their expression was positively
      correlated with HOTAIR expression. Finally, the functional assays indicated that
      the anticancer effects of miR-206 could be rescued by the simultaneous
      overexpression of either CCND1 or CCND2 in ovarian cancer. CONCLUSION: HOTAIR
      enhanced CCND1 and CCND2 expression by negatively modulating miR-206 expression
      and stimulating the proliferation, cell cycle progression, migration and invasion
      of ovarian cancer cells.

PMID- 30205384
TI  - miR-182-5p Promotes Growth in Oral Squamous Cell Carcinoma by Inhibiting CAMK2N1.
AB  - BACKGROUND/AIMS: Emerging evidence suggests that the propagation of oral squamous
      cell carcinoma (OSCC) is influenced by the abnormal expression of microRNAs
      (miRNAs). This study aimed to characterize the involvement of miR-182-5p in OSCC
      by targeting the calcium/ calmodulin-dependent protein kinase II inhibitor
      CAMK2N1. METHODS: miR-182-5p expression was quantified in OSCC tissues and cell
      lines with reverse transcription polymerase chain reaction (RT-PCR). Cell colony
      formation, Cell Counting Kit-8 (CCK-8), Ki-67, and nude mouse xenograft assays
      were used to characterize the role of miR-182-5p in the proliferation of OSCC. A
      miR-182-5p target gene was identified with western blotting, RT-PCR, and
      luciferase activity assays. OSCC patient survival based on CAMK2N1 expression was
      also analyzed. RESULTS: miR-182-5p was up-regulated in in vitro cell lines and in
      vivo clinical OSCC samples. CCK-8, colony formation, and Ki-67 assays revealed
      that miR-182-5p promoted the growth and proliferation of OSCC cells. miR-182-5p
      directly targeted CAMK2N1, as evidenced by luciferase assays and target
      prediction algorithms. CAMK2N1 operated as a tumor suppressor gene in patients
      with OSCC. Down-regulating miR-182-5p expression in the CAL-27 cell line restored
      CAMK2N1-mediated OSCC cell proliferation. miR-182-5p expression inhibited the
      activation of AKT, ERK1/2, and NF-kappaB. Mice injected with CAL-27 cells
      transfected with miR-182-5p-inhibitor demonstrated a significant increase in
      tumor size and weight and increased CAMK2N1 mRNA and protein expression compared
      with the miR-negative control group. CONCLUSION: The miR-182-5p-CAMK2N1 pathway
      can be potentially targeted to regulate the proliferation of OSCC cells.

PMID- 30205385
TI  - A Trypsin-Sensitive Proteoglycan from the Tapeworm Hymenolepis diminuta Inhibits
      Murine Neutrophil Chemotaxis in vitro by Suppressing p38 MAP Kinase Activation.
AB  - It has emerged that neutrophils can play important roles in the host response
      following infection with helminth parasites. Mice infected with the tapeworm,
      Hymenolepis diminuta, are protected from some inflammatory conditions,
      accompanied by reduced neutrophil tissue infiltration. Thus, the ability of a
      phosphate-buffered saline-soluble extract of the worm (H. diminuta extract [HdE])
      was tested for (1) its ability to activate murine neutrophils (Ca2+ mobilization,
      reactive oxygen species (ROS) and cytokine production); and (2) affect neutrophil
      chemotaxis in vitro to the penta-peptide, WKYMVm, the chemokine, KC, and
      leukotriene B4. HdE was not cytotoxic to neutrophils, elicited a Ca2+ response
      and ROS, but not, cytokine (KC, interleukin-10, tumour necrosis factor-alpha)
      generation. HdE is not a chemotactic stimulus for murine neutrophils. However, a
      heat- and trypsin-sensitive, acid-insensitive proteoglycan (sensitive to sodium
      metaperiodate) in the HdE significantly reduced neutrophil chemotaxis towards
      WKYMVm or KC, but not LTB4. The latter suggested that the HdE interfered with p38
      mitogen-activated protein kinase signalling, which is important in WKYMVm
      chemotaxis. Corroborating this, immunoblotting revealed reduced phosphorylated
      p38, and the downstream signal heat-shock protein-27, in protein extracts from
      HdE + WkYMVm treated cells compared to those exposed to the penta-peptide only.
      We speculate that HdE can be used to modify the outcome of neutrophilic disease
      and that purification of the bioactive proteoglycan(s) from the extract could be
      used as a template to design immunomodulatory drugs targeting neutrophils.

PMID- 30205386
TI  - Low Interleukin 10 Production at Birth Is a Risk Factor for Atopic Dermatitis in
      Neonates with Bifidobacterium Colonization.
AB  - BACKGROUND: Altered regulatory immune responses to microbial stimuli and
      intestinal colonization of beneficial bacteria early in life may contribute to
      the development of allergic diseases (e.g., atopic dermatitis [AD]). However, few
      reports have investigated these factors simultaneously. The purpose of this study
      was to analyze neonatal immune responses to microbial stimuli as well as
      intestinal colonization of beneficial bacteria, in relation to the development of
      AD in a birth cohort. METHODS: Pregnant women were recruited, and their infants
      were followed up until 7 months of age. Levels of interleukin (IL)-10 released
      from cord-blood mononuclear cells (CBMCs) stimulated with heat-killed gram
      positive bacteria (Bifidobacterium bifidum and Lactobacillus rhamnosus GG) and
      Lactobacillus-derived peptidoglycan were measured. Fecal Bifidobacterium counts
      at 4 days and 1 month were quantified using real-time polymerase chain reaction.
      The development of AD was determined by means of a questionnaire at 7 months of
      age. RESULTS: The levels of released IL-10 were significantly lower in infants
      with AD (n = 17) than in infants without AD (n = 53) for all stimuli. In infants
      with fecal Bifidobacterium, the incidence of AD was inversely associated with the
      release of IL-10 from cord blood mononuclear cells. CONCLUSION: Our findings
      suggest that impaired IL-10 production in response to microbial stimuli at birth
      may be associated with an increased risk of developing infantile AD, even in
      infants with early colonization of intestinal bifidobacteria.

PMID- 30205387
TI  - Temporal Regulation of Glomerular and Cortical Tubulointerstitial Genes Involved
      in the Development of Nephrotoxic Serum Nephritis.
AB  - BACKGROUND/AIMS: Murine nephrotoxic nephritis (NTN) is a well-established model
      resembling chronic kidney disease. Investigating gene expression patterns
      separately in the glomerular and cortical tubulointerstitial structure could
      provide new knowledge about structure-specific changes in expression of genes in
      the NTN model. METHODS: Glomerular, cortical tubulointerstitial and whole kidney
      tissues from mice subjected to nephrotoxic serum (NTS) or phosphate buffered
      saline (PBS) were collected on day 7, 21 and 42 using laser microdissection
      (LMD). Total RNA was extracted and subjected to nCounter NanoString. Histology,
      immunohistochemistry, in situ hybridization and/or quantitative real time PCR
      (qRT PCR) were performed to confirm regulation of selected genes. RESULTS: LMD
      provided detailed information about genes that were regulated differently between
      structures over time. Some of the fibrotic and inflammatory genes (Col1a1, Col3a1
      and Ccl2) were upregulated in both structures, whereas other genes such as Spp1
      and Grem1 were differentially regulated suggesting spatial pathogenic mechanisms
      in the kidney. Downregulation of cortical tubulointerstitium genes involved in
      iron metabolism was detected along with iron accumulation. CONCLUSION: This study
      demonstrates several regulated genes in pathways important for the pathogenesis
      of the NTN model and that LMD identifies structure-specific changes in gene
      expression during disease development. Furthermore, this study shows the benefits
      of isolating glomeruli and cortical tubulointerstitium in order to identify gene
      regulation.

PMID- 30205388
TI  - Eculizumab Modifies Outcomes in Adults with Atypical Hemolytic Uremic Syndrome
      with Acute Kidney Injury.
AB  - BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is a rare disease
      associated with congenital or acquired genetic abnormalities that result in
      uncontrolled complement activation, leading to thrombotic microangiopathy and
      kidney failure. Until recently, the only treatment was plasma exchange or plasma
      infusion (PE/PI), but 60% of patients died or had permanent kidney damage despite
      treatment. Eculizumab, a complement inhibitor, has shown promising results in
      aHUS. However, data are mainly extracted from case reports or studies of
      heterogeneous cohorts, and no direct comparison with PE/PI is available. METHODS:
      An observational retrospective study of adult, dialysis-dependent aHUS patients
      with acute kidney injury (AKI) who were treated with either PE/PI alone or with
      second-line eculizumab in our center. We compared the effect of PE/PI and
      eculizumab on kidney function, hypertension, proteinuria, hematologic values,
      relapse, and death. RESULTS: Thirty-one patients were included (females, 18;
      sporadic aHUS, 29; mean age, 46 +/- 20 years). Twenty-six patients were treated
      with PE/PI alone, and 5 were deemed to be plasma-resistant and received
      eculizumab after stopping PE/PI. Among patients receiving eculizumab, 80%
      attained complete recovery of kidney function, 100% stopped dialysis, 20% had
      decreased proteinuria, and no patient relapsed (vs. 38.5, 50, 15.4, and 11.5%,
      respectively, of patients receiving only PE/PI). At 1-year of follow-up, no
      deaths had occurred in either group. CONCLUSION: Eculizumab shows greater
      efficacy than PE/PI alone for the treatment of adult aHUS patients with AKI.
      Prospective studies and meta-analyses are warranted to confirm our findings and
      set guidelines for treatment, monitoring, and maintenance.

PMID- 30205389
TI  - Jargonaphasia: A Systematic Overview and Characterization in Primary Progressive
      Aphasia.
AB  - This study provides a literature-based overview of jargonaphasia in primary
      progressive aphasias (PPA) exploring its occurrence, phenotypes, and anatomical
      underpinnings, while adding 2 novel cases with prototypical jargon. We report 26
      jargonaphasia cases, initially diagnosed with semantic or logopenic PPA,
      resulting in semantic or phonological jargon, respectively. Brain damage in
      literature and our cases encompassed superior temporal cortices involved in
      language monitoring, the temporal-parietal junction for phonological jargon and
      temporal poles for semantic jargon. Our findings show that jargonaphasia is an
      infrequent language feature in PPA, comprises exclusively semantic and
      phonological jargon related to semantic and logopenic PPA, whereas no syntactic
      jargon case was identified in nonfluent/agrammatic PPA. Our outcomes allow for
      classifying jargonaphasic patients within the spectrum of PPA variants, thus
      providing indicators of the underlying neuropathology.

PMID- 30205390
TI  - Immunophenotypes of Ductal Epithelial Cells in Advanced Pancreatic Ductal
      Adenocarcinoma.
AB  - BACKGROUND/AIMS: In this report, we aimed to investigate the distribution and
      characterization of biomarker-immunolabeled ductal epithelium in advanced
      pancreatic ductal adenocarcinoma (PDAC). DESIGN: Eighteen patients with PDAC were
      medically diagnosed prior to being treated periodically. All clinical records
      were collected and assayed. The PDAC samples were subjected to routine
      biochemical tests and immuno-stains of immunohistochemistry and
      immunofluorescence. RESULTS: As results, immunohistochemical findings indicated
      pancreatic ductal cells in PDAC showed plenty of Ki-67, P53, RP, SAM positive
      cells expressed in nuclei. In addition, ductal epithelial cells exhibited
      numerous positive cells of CK7, 18, 19, 20 biomarkers, respectively.
      Interestingly, compared to non-PDAC controls, immunostaining results showed that
      endocrine hormones were positively expressed in pancreatic ducts of PDAC,
      characterized with increased insulin-, Ngn3-, PDX1-fluorescence-labeled cells,
      and reduced F-box and WD-40 domain protein 7 (Fbxw7)-labeled cells in ducts.
      CONCLUSION: These clinicopathologic findings preliminarily disclose that there
      may be a potential for insulin-producing cells in PDAC, possibly through
      negatively inducing Fbxw7 ubiquitination in pancreatic ducts.

PMID- 30205392
TI  - Endpoints for Clinical Trials of Acute Kidney Injury.
AB  - BACKGROUND: The selection of appropriate endpoints is critical to the success of
      any clinical trial. Endpoints need to be precisely defined and need to provide an
      appropriate balance between sensitivity for detection of the effects of the
      intervention of interest and specificity for the outcome of interest. SUMMARY: In
      acute kidney injury (AKI), the 2 most common endpoints utilized either rely on
      small, short-term changes in serum creatinine or are a composite of longer term
      major adverse kidney events, including death, need for dialysis, and a persistent
      decline in kidney function. Key messages: Numerous issues affecting the potential
      utility of these endpoints are discussed that need to be carefully considered
      when selecting appropriate endpoints in the design of AKI trials.

PMID- 30205391
TI  - Long Non-Coding RNA PVT1/miR-150/ HIG2 Axis Regulates the Proliferation, Invasion
      and the Balance of Iron Metabolism of Hepatocellular Carcinoma.
AB  - BACKGROUND/AIMS: To investigate the biological roles and underlying molecular
      mechanisms of long non-coding RNA (lncRNA) PVT1 in Hepatocellular carcinoma
      (HCC). METHODS: qRT-PCR was performed to measure the expression of miRNA and
      mRNA. Western blot was performed to measure the protein expression. CCK-8 assay
      was performed to determine cell proliferation. Flow cytometry was performed to
      detect cell apoptosis. Wounding-healing assay and Transwell assay was performed
      to detect cell migration and invasion. Dual luciferase reporter assay was
      performed to verify the target relationship. Quantichrom iron assay was performed
      to check uptake level of cellular iron. RESULTS: PVT1 expression was up-regulated
      in HCC tissues and cell lines. Function studies revealed that PVT1 knockdown
      significantly suppressed cell proliferation, migration and invasion, and induced
      cell apoptosis in vitro. Furthermore, PVT1 could directly bind to microRNA (miR)
      150 and down-regulate miR-150 expression. Hypoxia-inducible protein 2 (HIG2) was
      found to be one target gene of miR-150, and PVT1 knockdown could inhibit the
      expression of HIG2 through up-regulating miR-150 expression. In addition, the
      expression of miR-150 was down-regulated, while the expression of HIG2 was up
      regulated in HCC tissues and cell lines. Moreover, inhibition of miR-150 could
      partly reverse the biological effects of PVT1 knockdown on proliferation,
      motility, apoptosis and iron metabolism in vitro, which might be associated with
      dysregulation of HIG2. In vivo results showed that PVT1 knockdown suppressed
      tumorigenesis and iron metabolism disorder by regulating the expression of miR
      150 and HIG2. CONCLUSION: Taken together, the present study demonstrates that
      PVT1/miR-150/HIG2 axis may lead to a better understanding of HCC pathogenesis and
      provide potential therapeutic targets for HCC.

PMID- 30205393
TI  - Panax Quinquefolium Saponins Attenuate Myocardial Dysfunction Induced by Chronic
      Ischemia.
AB  - BACKGROUND/AIMS: Previous studies in rat models of myocardial ischemia showed
      that Panax quinquefolium saponins (PQS) could attenuate ischemic/reperfusion
      injury, increase vessel density and improve cardiac function. In the current
      study, we examined whether PQS could attenuate myocardial dysfunction in a swine
      model of chronic myocardial ischemia (CMI). METHODS: CMI was established in Bama
      mini-pigs by placing amroid constrictor on the left anterior descending artery
      (LAD). Starting from 2 months after the surgery, pigs randomly received PQS (30
      mg/kg/day), atorvastatin (1.5 mg/kg/day), or no drug for one month (n=6). A group
      of pigs receiving sham surgery was included as an additional control. Glucose
      utilization was assessed with positron emission tomography-computer tomography
      (PET-CT). Cardiac function was assessed with echocardiography. Myocyte size,
      nuclear density, and arteriolar density were examined in tissue section obtained
      from the ischemia area. Potential molecular targets of PQS were identified using
      proteomic analysis with isobaric tags for relative and absolute quantitation
      (iTARQ) and network pharmacology. RESULTS: In comparison to the sham controls,
      pigs implanted with ameroid constrictor had decreased ventricular wall motion,
      left ventricular ejection fraction (LVEF), and glucose utilization. PQS
      significantly increased cardiac function and glucose utilization. Arteriole
      density and myocyte nuclear density were increased. Myocyte diameter was
      decreased. PQS also attenuated the CMI-induced change of protein expression
      profile. The effects of atorvastatin were generally similar to that of PQS.
      However, PQS attenuated the reduction of left ventricular systolic WT induced by
      CMI more robustly than atorvastatin. CONCLUSION: The results from the current
      study supports the use of PQS in patients with coronary artery disease.

PMID- 30205394
TI  - Identification and Functional Evaluation of miR-4633-5p as a Biomarker and Tumor
      Suppressor in Metastatic Melanoma.
AB  - BACKGROUND/AIMS: Sinonasal mucosal melanoma (SMM) is a rare but extremely
      aggressive disease. Interestingly, however, as lethal as SMM, a few patients
      could survive for over 5 years without metastasis. However, biomarkers for
      metastatic SMM are lacking. METHODS: Laser-capture microdissection combined with
      microRNA microarray and RT-qPCR was performed in formalin-fixed paraffin-embedded
      tissue samples from SMM patients whose follow-up studies were carried out in
      parallel. In vitro cell proliferation and invasion assays, gelatin zymography,
      western blot analysis and RT-qPCR were performed in melanoma cell lines. RESULTS:
      In the discovery stage, miR-4633-5p expressed differentially in sinonasal mucosal
      melanoma patients with short and long disease-specific survival. Subsequent large
      sample validation revealed that expression of miR-4633-5p was lower in metastatic
      SMM than in non-metastatic patients (P< 0.001). Moreover, miR-4633-5plow was able
      to identify metastatic SMM with specificity of 100% (5/5) and sensitivity of
      87.5% (21/24). Multivariate analysis further pinpointed miR-4633-5p as an
      independent marker for metastasis (relative risk: 54.22, P< 0.001). In vitro,
      overexpression of miR-4633-5p suppressed the growth and invasiveness of melanoma
      cells through inhibiting activation of Akt pathway and secretion of MMP2, while
      knockdown of miR-4633-5p reversed the inhibitory effects. CONCLUSION: Our
      findings underpin miR-4633-5p as a predictive biomarker in metastatic SMM and a
      pivotal tumor suppressor that negatively regulates the invasive growth of
      melanoma cells. Quantitative detection of miR-4633-5p can diagnostically predict
      the risk of metastasis in SMM patients, which, in turn, may lead to more
      personalized treatment with better prognosis.

PMID- 30205395
TI  - Octreotide Alleviates Autophagy by Up-Regulation of MicroRNA-101 in Intestinal
      Epithelial Cell Line Caco-2.
AB  - BACKGROUND: Intestinal mucositis is a common side-effect after anti-cancer
      therapy, which may greatly restrict the therapeutic effects. We aimed to explore
      the functional role of octreotide (OCT) in lipopolysaccharide (LPS)-induced
      autophagy of human intestinal epithelial cells as well as the underlying
      mechanisms. METHODS: Cell viability and expression of proteins related to
      autophagy, AMPK and the mTOR pathway in LPS-treated Caco-2 cells were determined
      by CCK-8 assay and Western blot analysis, respectively. Effects of OCT on LPS
      induced alterations as well as miR-101 expression were measured. Then, miR-101
      was aberrantly expressed, and whether OCT alleviated LPS-induced autophagy
      through miR-101 was tested. Next, whether TGF-beta-activated kinase 1 (TAK1) was
      involved in the regulation of miR-101 in LPS-induced autophagy was studied.
      Effects of OCT on monolayer permeability and tight junction level were analyzed
      via measuring transepithelial electrical resistance (TEER) and expression of
      tight junction proteins. RESULTS: LPS reduced cell viability and increased
      autophagy through activating AMPK and inhibiting the mTOR pathway in Caco-2
      cells. OCT alleviated LPS-induced alterations and repressed degradation of
      autophagosome. Then, we found that OCT affected autophagy through up-regulating
      miR-101 in LPS-treated cells. Moreover, miR-101-induced inactivation of AMPK and
      activation of the mTOR pathway in LPS-treated cells were reversed by inhibition
      of TAK1 phosphorylation. Finally, we found miR-101 was up-regulated in
      differentiated cells, and OCT protected the monolayer permeability and tight
      junction level. CONCLUSION: OCT repressed autophagy through miR-101-mediated
      inactivation of TAK1, along with inactivation of AMPK and activation of the mTOR
      pathway in LPS-treated Caco-2 cells.

PMID- 30205397
TI  - Safety of Carbon Dioxide Insufflation during Endoscopic Submucosal Dissection for
      Esophageal Squamous Cell Carcinoma.
AB  - BACKGROUND: Pulmonary dysfunction often accompanies esophageal squamous cell
      carcinoma (SCC). AIMS: This study examined the use of carbon dioxide (CO2)
      insufflation and its safety during esophageal endoscopic submucosal dissection
      (ESD) while under conscious sedation. METHODS: ESD using CO2 insufflation (1.4
      L/min) was performed in 102 consecutive esophageal SCC patients. Patients with a
      forced expiratory volume of 1.0 s/forced vital capacity (FEV1.0%) < 70% or a
      vital capacity < 80% were defined as having pulmonary dysfunction. Transcutaneous
      partial pressure of CO2 (PtcCO2) was recorded before, during, and after ESD.
      RESULTS: A history of smoking was found in 90 patients (88%), while 43 patients
      (42%) had pulmonary dysfunction. No significant differences were found between
      the pulmonary dysfunction and normal groups for the baseline PtcCO2 before ESD,
      peak PtcCO2 during ESD, and median PtcCO2 after ESD. There was a significant
      correlation between the PtcCO2 elevation from baseline and the ESD procedure time
      (r = 0.32, p < 0.01), with the correlation for the pulmonary dysfunction group
      much stronger (r = 0.39, p < 0.05) than that for the normal group (r = 0.30, p <
      0.01). Neither of the groups exhibited any differences for either the
      complication incidence or the hospital stay. CONCLUSIONS: Although the use of CO2
      insufflation during esophageal ESD under conscious sedation is safe with regard
      to the risk of complications, longer procedure times can potentially induce CO2
      retention in patients with obstructive lung disease. Thus, it is necessary to
      both shorten the procedure times and perform CO2 monitoring.

PMID- 30205396
TI  - Weather, Weather Changes and the Risk of Bell's Palsy: A Multicenter Case
      Crossover Study.
AB  - BACKGROUND: To evaluate if weather or changes in weather are risk factors for
      Bell's palsy (BP) as exposure to draught of cold air has been popularly
      associated with the occurrence of BP. METHODS: Using a multicenter hospital-based
      case-crossover study, we analyzed the association between ambient temperature,
      atmospheric pressure, relative air humidity or their 24 h changes and the risk
      for BP in 825 patients or subgroups. RESULTS: One day following a 24 h increase
      in atmospheric pressure of more than 6 hPa, the risk for BP increased by 35% (OR
      1.35; 95% CI 1.03-1.78) in the overall population. The risk for BP more than
      doubled in patients with diabetes mellitus after rapid variations in ambient
      temperature, independent of the direction (temperature decrease > 2.25 degrees C;
      OR 2.15; 95% CI 1.08-4.25; temperature increase between 0.75 and 2.25 degrees C;
      OR 2.88; 95% CI 1.63-5.10). CONCLUSIONS: Our findings support the hypothesis of
      an association between certain weather conditions and the risk for BP with acute
      changes in atmospheric pressure and ambient temperature as the main risk factors.
      Additionally, contrasting results for risk of BP after temperature changes in the
      diabetic and non-diabetic subgroups support the paradigm of a diabetic facial
      palsy as a distinct disease entity.

PMID- 30205398
TI  - Prevalence of Apolipoprotein E Polymorphisms in Alzheimer's Disease, Mild
      Cognitive Impairment, and Healthy Elderly: A Northern Greece Study.
AB  - BACKGROUND: Apolipoprotein E epsilon4 allele (APOEepsilon4) is a major genetic
      risk factor for Alzheimer's disease (AD). APOEepsilon4 carriers have a higher
      risk of cognitive impairment and AD in a gene dose-dependent manner. The above
      notion is investigated in the Greek population. METHODS: A sample of 1,703
      subjects (967 AD patients, 576 mild cognitive impairment [MCI] and 160 Healthy
      Elderly), was genotyped for APOE from 2008 to 2017. DNA was extracted from
      peripheral blood using the QIAamp Blood DNA purification kit (Qiagen Inc., USA).
      Descriptive statistics, one-way analysis of variance with Bonferroni post hoc
      tests, Pearson chi-square test, and binary logistic regression models were used
      for the statistical analysis. RESULTS: The APOE genotype and allele frequencies
      in AD group were significantly different from those in the Control and MCI
      groups. The frequencies of epsilon4/4 homozygotes were 1.9, 1.6, and 5.7%, while
      the epsilon4/- carriers' distribution was 22.5, 24.1, and 37.4% in the Control,
      MCI, and AD groups respectively. The estimated odds of epsilon4/4 for AD was
      5.731-fold higher compared to the estimated odds of epsilon3/3. The interaction
      between gender and APOE did not have a significant effect on the odds for MCI (p
      = 0.942) and AD (p = 0.984). CONCLUSION: In Greece, APOE epsilon4 presence is
      related to an increased risk for AD in a dose-related manner. Contrary to long
      standing views, men and women with the APOE epsilon4 genotype have nearly the
      same odds of developing MCI and AD.

PMID- 30205399
TI  - A Time-Series Analysis of Severe Burned Injury of Skin Gene Expression Profiles.
AB  - BACKGROUND/AIMS: Major burn injury is one of the main severe forms of wound which
      lead to a mass of clinical debilitation, this study was to identify core
      biomarkers for the recovery of severe burned injury. METHODS: Gene expression
      profiles (GSE19743) from the Gene Expression Omnibus (GEO) was downloaded,
      followed by background correction, normalization of raw microarray dataset and
      identification of differential expression genes (DEGs) . Soft clustering of DEGs
      was used for the screening of gene clusters that with sustained increasing (SIG)
      and decreasing expression (SDG) profiles along with the recovery process of
      burned injury. The significantly enriched Gene Ontology (GO) terms and Kyoto
      Encyclopedia of Genes and Genomes (KEGG) pathways of SIGs and SDGs were obtained
      through the Database for Annotation, Visualization, and Integrated Discovery
      (DAVID), based on which the miRNA-gene regulation network for SIGs and SDGs were
      constructed from the miRWalk database. RESULTS: Ten clusters were obtained
      through soft clustering. The SIGs and SDGs were found to be closely associated
      with the biological processes of immune system. The miRNA-gene regulation network
      analysis suggested different roles between SIGs and SDGs in the recovery of
      severe burned injury. Furthermore, a bunch of important biomarkers were
      identified, which would be helpful in the treatment of burned patients.
      CONCLUSION: Our current findings suggest an interesting molecular link between
      transcriptional regulation potentially involved in immunosuppressive state after
      major burn injury, which warrants further exploration for their utilization in
      the treatment of major burn injury.

PMID- 30205400
TI  - Assessment of Long-Term Efficacy and Safety of Adalimumab in Patients with
      Ulcerative Colitis: Results from a 6-Year Real-World Clinical Practice.
AB  - BACKGROUND: Although evidence for the short- to medium-term efficacy of
      adalimumab in ulcerative colitis (UC) patients is emerging, there are a limited
      number of reports on the long-term efficacy of adalimumab. This study was to
      understand baseline demographic features, which potentially could be risk factors
      for relapse or colectomy following induction of remission by adalimumab in UC
      patients. Additionally, factors affecting long-term outcomes were to be
      identified. METHODS: Twenty-one patients with UC who had been treated with
      adalimumab were reviewed retrospectively. Comparative analyses were undertaken by
      factoring steroid withdrawal versus non-withdrawal, long-term remission versus
      relapse following remission, and requiring surgical intervention for UC versus
      surgery-free. RESULTS: Adalimumab treatment was associated with steroid tapering
      in steroid-dependent cases in the long term. Of the 14 patients in whom clinical
      remission was achieved, the cumulative nonrelapse survival rate at 350 weeks was
      43.8% and the cumulative nonoperative survival rate was 85.7%. Risk factors for
      surgery included intolerance to salicylates (p = 0.005) and past treatment with
      tacrolimus (p = 0.023). CONCLUSIONS: Adalimumab treatment was associated with
      long-term efficacy in patients with mild UC - patients achieved a high cumulative
      nonoperative survival rate over a long period of time, beyond 6 years.

PMID- 30205401
TI  - Levels of Proinflammatory Cytokines, Oxidative Stress, and Tissue Damage Markers
      in Patients with Acute Heart Failure with and without Cardiorenal Syndrome Type
      1.
AB  - BACKGROUND: Cardiorenal syndrome type 1 (CRS type 1) is characterized by a rapid
      worsening of cardiac function leading to acute kidney injury (AKI). Inflammation
      and oxidative stress seem to play a pivotal role in its pathophysiology. In this
      in vivo study, we examined the putative role of inflammation and humoral markers
      in the pathogenesis of the CRS type 1. METHODS: We enrolled 53 patients with
      acute heart failure (AHF); 17 of them developed AKI (CRS type 1). The cause of
      AKI was presumed to be related to cardiac dysfunction after having excluded other
      causes. We assessed the plasma levels of proinflammatory cytokines (TNF-alpha, IL
      6, IL-18, sICAM, RANTES, GMCSF), oxidative stress marker (myeloperoxidase, MPO),
      brain natriuretic peptide (BNP), and neutrophil gelatinase-associated lipocalin
      (NGAL) in AHF and CRS type 1 patients. RESULTS: We observed a significant
      increase in IL-6, IL-18, and MPO levels in CRS type 1 group compared to AHF (p <
      0.001). We found higher NGAL at admission in the CRS type 1 group compared to the
      AHF group (p = 0.008) and a positive correlation between NGAL and IL-6
      (Spearman's rho = 0.45, p = 0.003) and between IL-6 and BNP (Spearman's rho =
      0.43, p = 0.004). We observed lower hemoglobin levels in CRS type 1 patients
      compared to AHF patients (p < 0.05) and inverse correlation between hemoglobin
      and cytokines (IL-6: Spearman's rho = -0.38, p = 0.005; IL-18: Spearman's rho = 
      0.32, p = 0.02). CONCLUSION: Patients affected by CRS type 1 present increased
      levels of proinflammatory cytokines and oxidative stress markers, increased
      levels of tissue damage markers, and lower hemoglobin levels. All these factors
      may be implicated in the pathophysiology of CRS type 1 syndrome.

PMID- 30205402
TI  - Effect of Chemotherapy on Removal of Indwelling Pleural Catheters in Breast
      Cancer Patients with Malignant Pleural Effusions.
AB  - BACKGROUND: Indwelling pleural catheters (IPC) are commonly used in the
      management of malignant pleural effusions (MPE). The effect of systemic
      chemotherapy on IPC removal has not been reported previously. OBJECTIVES: The
      purpose of this study is to identify the effect of chemotherapy on the removal of
      IPCs in breast cancer patients with MPEs. METHODS: In this retrospective cohort
      study at an academic tertiary-care center, patients with breast cancer and MPE
      who received an IPC between 2006 and 2016 were identified from a prospectively
      collected database. Patient chemotherapy data were obtained, as well estrogen
      receptor (ER) and human epidermal growth factor receptor-2 status at the time of
      diagnosis. Patients receiving chemotherapy while their IPC was in situ were
      compared to those who did not. The primary outcome was time to IPC removal. All
      patients were followed until IPC removal or death. RESULTS: A total of 207
      patients and 216 IPCs were included in the analysis. There was no difference in
      time to IPC removal between the chemotherapy and no-chemotherapy groups (HR 0.73,
      95% CI 0.50-1.07, p = 0.10) or rate of IPC removal (OR 1.16, 95% CI 0.68-1.98, p
      = 0.59). The risk of IPC infection was not different between patients who
      received chemotherapy and those who did not (RR 0.57, 95% CI 0.06-5.39, p =
      0.48). CONCLUSIONS: Treatment with chemotherapy with an IPC in situ was not
      associated with a reduced time to IPC removal in our breast cancer population.
      IPC insertion in patients receiving chemotherapy is safe and not associated with
      an increased risk of infection.

PMID- 30205403
TI  - Evaluation of Hearing and Balance Functions of Patients with Sickle Cell Anemia.
AB  - INTRODUCTION: Sickle cell anemia is a disease characterized by a wide vaso
      occlusive incident from micro-vascular incident to muscularactivity. The cochlear
      function can also get affected by this vaso-occlusion. OBJECTIVE: It is aimed at
      determining what kind of effects sickle cell anemia has on hearing and balance
      system. METHODS: This study has been conducted on 46 patients with sickle cell
      anemia and 45 healthy individuals. For all participants, their pure tone hearing
      thresholds and videonystagmography (VNG) findings have been determined in 17
      frequencies between 125-16.000 Hz. RESULTS: All hearing thresholds between 125
      and 16,000 Hz, pure tone averages of patients with sickle cell anemia have been
      found statistically significant to be higher than the corresponding values in the
      control group(p < 0.05). The normal hearing rate of patients with sickle cell
      anemia has been determined to be 71.1% conductive hearing loss (CHL) to be 4.4%,
      sensorineural hearing loss (SNHL) to be 22.2%, and mixed type hearing loss to be
      2.2% in right ear; the normal hearing rate has been determined to be 71.1%, CHL
      to be 2.2%, SNHL to be 22.2%, and mixed type hearing loss to be 4.4% in left ear.
      Statistically significant difference has not been found between head shake,
      spontaneous nystagmus, optokinetic, tracking test batteries, static and dynamic
      positional tests used in VNG, saccade accuracy and saccade peak velocity, which
      are saccadic test findings of 2 groups. However, saccadic latency, which is a
      saccadic test finding, has been determined to be longer in patients with sickle
      cell anemia in comparison to the control group. CONCLUSION: While sickle cell
      anemia causes hearing deficits, it does not have any effect on the central or
      peripheral vestibular system.

PMID- 30205404
TI  - Chinese Angelica Polysaccharide (CAP) Alleviates LPS-Induced Inflammation and
      Apoptosis by Down-Regulating COX-1 in PC12 Cells.
AB  - BACKGROUND/AIMS: Chinese angelica polysaccharide (CAP) is the main effective
      ingredient of angelica sinensis and exerts anti-inflammatory and anti-apoptotic
      effects on many diseases. This study aimed to explore the pharmacological
      potential of CAP on spinal cord injury (SCI). METHODS: PC12 cells were pretreated
      by CAP and were subjected to LPS. Transfection was performed to alter the
      expression of COX-1. Cell viability and apoptotic cell rate were measured by CCK
      8 and flow cytometry respectively. qRT-PCR and western blot analysis were
      performed to assess the expression changes of pro-inflammatory cytokines,
      apoptosis-related factor and core kinases in PI3K/AKT pathway. RESULTS: LPS
      stimulation induced significant cell damage in PC12 cells as cell viability was
      repressed, apoptosis was induced and the expression levels of IL-1beta, IL-6, IL
      8, and TNF-alpha were increased. CAP pretreatment protected PC12 cells against
      LPS-induced cell damage. Meanwhile CAP treatment reduced the expression of COX-1
      even in LPS-stimulated PC12 cells. More importantly, COX-1 overexpression
      abolished the protective effects of CAP on LPS-injured PC12 cells. Finally,
      Western blot analytical results showed that CAP activated PI3K/AKT pathway also
      in a COX-1-dependent manner. CONCLUSION: CAP exerted anti-apoptotic and anti
      inflammatory effects on LPS-injured PC12 cells via down-regulation of COX-1.

PMID- 30205406
TI  - Community Acquired Acute Kidney Injury in Mansoura Nephrology Dialysis Unit: One
      Year Prospective Observational Study.
AB  - AIM: Acute kidney injury (AKI) is a major health problem with poor patient
      prognosis. We evaluated the clinical characteristics, risk factors, associated
      comorbidities, and outcomes of AKI patients. METHODOLOGY: A single-center
      prospective observational study. The patients were admitted in Mansoura
      Nephrology and Dialysis Unit over a period of 1 year from January to December,
      2016. Patients were diagnosed as AKI or AKI in addition to chronic kidney disease
      according to the creatinine criteria of KDIGO 2013. All patients were subjected
      to complete history taking, physical examination, and full laboratory and pelvi
      abdominal ultrasound investigations. The study outcomes were all-cause hospital
      mortality, and recovery of renal function. Predictors of mortality were assessed
      using multivariate logistic regression analysis. The study was reviewed and
      approved by local Ethical Committee of IBR. RESULTS: We evaluated 199 (96 males
      plus 103 females) aged between 18 and 88 years old. Dehydration was the commonest
      precipitating factor for AKI in our patients (68.8%) and Oliguria was the
      commonest symptom present in 47.7% of patients. Intravenous fluids were received
      by 79.9% of patients, 22.6% of patients received diuretics, and 33.7% received
      renal replacement therapy in the form of intermittent hemodialysis. Death
      occurred in 25 patients (13.16%) and 69 (36.32%) showed no renal recovery. Shock
      and sepsis were the most significant predictors of mortality. Conclusion:
      Community acquired AKI is a major health problem with high morbidity and
      mortality.

PMID- 30205405
TI  - Heart Rate Variability During Early Mobilization in Patients with Acute Ischemic
      Stroke.
AB  - Autonomic dysfunction is one of the predictors of poor outcome in patients with
      acute ischemic stroke. We compared the heart rate variability (HRV) during early
      mobilization in patients with or without neurological deterioration (ND). We
      enrolled 7 acute ischemic patients with ND and 14 without ND and measured their
      HRV in the rest and mobilization by electrocardiography. There was a significant
      difference in sympathetic nervous activity during mobilization between the 2
      groups. However, no significant differences in blood pressure, heart rate, and
      parasympathetic nerve activity were observed. In patients with acute ischemic
      stroke, it is likely that the increase in sympathetic nervous activity during
      mobilization is associated with ND.

PMID- 30205407
TI  - Suppression of Long Non-Coding RNA LINC00652 Restores Sevoflurane-Induced
      Cardioprotection Against Myocardial Ischemia-Reperfusion Injury by Targeting GLP
      1R Through the cAMP/PKA Pathway in Mice.
AB  - BACKGROUND/AIMS: Long non-coding RNA (lncRNA) and glucagon-like peptide 1
      receptor (GLP-1R) are crucial for heart development and for adult heart
      structural maintenance and function. Herein, we performed a study to explore the
      effect of lncRNA LINC00652 (LINC00652) on myocardial ischemia-reperfusion (I/R)
      injury by targeting GLP-1R through the cyclic adenosine monophosphate-protein
      kinase A (cAMP/PKA) pathway. METHODS: Bioinformatics software was used to screen
      the long-chain non-coding RNAs associated with myocardial ischemia-reperfusion
      and to predict target genes. The mRNA and protein levels of LINC00652, GLP-1R and
      CREB were detected by RT-qPCR and western blotting. In order to identify the
      interaction between LINC00652 and myocardial I/R injury, the cardiac function,
      the hemodynamic changes, the pathological changes of the myocardial tissues, the
      myocardial infarct size, and the apoptosis of myocardial cells of mice were
      measured. Meanwhile, the levels of serum IL-1beta and TNF-alpha were detected.
      RESULTS: LINC00652 was overexpressed in the myocardial cells of mice with
      myocardial I/R injury. GLP-1R is the target gene of LINC00652. We also determined
      higher levels of LINC00652 and GLP-1R in the I/R modeled mice. Additionally, si
      LINC00652 decreased cardiac pathology, infarct size, apoptosis rates of
      myocardial cells, and levels of IL-1beta and TNF-alpha, and increased GLP-1R
      expression cardiac function, normal hemodynamic index, and the expression and
      phosphorylation of GLP-1R and CREB proteins. CONCLUSION: Taken together, our key
      findings of the present highlight LINC00652 inhibits the activation of the
      cAMP/PKA pathway by targeting GLP-1R to reduce the protective effect of
      sevoflurane on myocardial I/R injury in mice.

PMID- 30205408
TI  - CT-Fluoroscopic Guidance for Performance of Targeted Transbronchial Cryobiopsy: A
      Preliminary Report.
AB  - BACKGROUND: Bronchoscopic transbronchial cryobiopsy is increasingly used for the
      histological assessment of diffuse parenchymal lung disease. Diagnostic
      performance may be improved by more accurate targeting of biopsy to radiologic
      abnormalities, and complication rates may be reduced by avoiding biopsy of pleura
      or larger vessels. OBJECTIVES: To report the preliminary experience of using CT
      fluoroscopic guidance for accurate targeting of bronchoscopic transbronchial
      cryobiopsy. METHODS: Bronchoscopic cryobiopsy was performed in a hybrid CT
      theatre. 3D CT images were acquired following positioning of the cryoprobe in a
      distal airway segment. Where cryoprobe position was observed to be too close to
      the chest wall/diaphragm pleura, or not within the region of interest within the
      lung parenchyma, re-positioning of probe was undertaken and repeat 3D images were
      acquired to confirm positioning prior to cryobiopsy. RESULTS: CT-fluoroscopic
      transbronchial cryobiopsy was successfully performed in 4 patients: 3 patients
      with interstitial lung infiltrates, and one with an enlarging left upper lobe
      mass. Images were reviewed following each acquisition to accurately assess the
      probe position within the lung parenchyma, and relative to other thoracic
      structures. Intra-procedural imaging was of sufficient quality to allow the
      accurate positioning of the cryoprobe tip with respect to both the parenchymal
      region of interest and pleural surfaces. No complications were experienced, and
      all procedures yielded diagnostic specimens. CONCLUSIONS: Our preliminary
      experience confirms the feasibility of performing transbronchial cryobiopsy under
      CT-fluoroscopic guidance. Accurate targeting of transbronchial cryobiopsy may be
      achieved using CT-fluoroscopic guidance. Positioning of the probe tip, both with
      respect to parenchymal region of interest and to pleural surfaces, can be
      established with high accuracy.

PMID- 30205409
TI  - Anti-IFN-gamma Antibody Promotes Osteoclastogenesis in Human Bone Marrow Monocyte
      Derived Macrophages Co-Cultured with Tuberculosis-Activated Th1 Cells.
AB  - BACKGROUND/AIMS: Tuberculosis induces bone loss and activates Th1 cells that play
      an important role in the host defense of Bacille Calmette-Guerin tuberculosis
      vaccine. However, the role of tuberculosis-activated Th1 cells in differentiation
      of osteoclast precursors to osteoclasts is unclear. As secretion of IFN-gamma in
      Th1 cells is induced by tuberculosis, we aimed to investigate the role of anti
      IFN-gamma antibody on the differentiation and activation of osteoclasts in bone
      marrow monocyte-derived macrophages (BMMs). METHODS: BMMs were isolated and co
      cultured with CD4+T helper 1 cells (Th1 cells), pretreated with anti-IFN-gamma
      antibody. Then, cell proliferation, expression and release of cytokines,
      formation of actin ring, differentiation of osteoclasts and bone resorption
      function were measured by CCK8 assay, qRT-PCR/Western blot/flow cytometry, ELISA,
      immunofluorescence, tartrate-resistant acidic phosphatase (TRAP) staining and
      bone absorbance assay, respectively. RESULTS: Anti-IFN-gamma antibody inhibited
      the cell viability of BMMs, and induced the expressions of RANKL, TNF-alpha, NF
      kappaB and TRAF6 in BMMs. In addition, it led to increased expression levels of
      RANK on cell surfaces, and increased production of RANKL, TNF-alpha, MCP-1 and
      SDF-1. Anti-IFN-gamma antibody also induced the expression of osteoclast
      differentiation factor and actin ring formation, but inhibited the expression of
      osteoprotegerin. TRAP staining and bone resorption assays showed that anti-IFN
      gamma antibody induced an increase in osteoclast formation and bone resorption.
      CONCLUSION: The anti-IFN-gamma antibody induced osteoclast formation, and is
      probably mediated by RANKL-induced activation of NF-kappaB, that induces TRAF6 in
      the RANKL-RANK signaling pathway. Our data suggest an inhibitory role for IFN
      gamma in osteoclast formation induced by tuberculosis.

PMID- 30205411
TI  - Incidence and Predictors of Tracheobronchial Tuberculosis in Pulmonary
      Tuberculosis: A Multicentre, Large-Scale and Prospective Study in Southern China.
AB  - BACKGROUND: Patients with pulmonary tuberculosis (PTB) have a high risk of
      concomitant tracheobronchial tuberculosis (TBTB), which commonly causes severe
      complications such as tracheobronchial stenosis. The prevalence and predictors of
      TBTB in China remain unclear due to the lack of prospective and large-scale
      studies. OBJECTIVES: To investigate the incidence of TBTB in PTB patients in
      southern China, and elucidate the predictors of TBTB and related tracheobronchial
      stenosis. METHODS: We prospectively performed bronchoscopy in PTB patients to
      diagnose TBTB at four medical centres in southern China from September 2015 to
      August 2016. Clinical and epidemiological data were recorded and analysed to
      determine predictors of TBTB and related tracheobronchial stenosis. RESULTS: A
      total of 345 (23.9%) of the 1,442 PTB patients undergoing bronchoscopy were
      diagnosed with TBTB. Female sex (OR 2.53), age < 50 years (OR 1.88), living in
      urban (OR 2.19), diabetes (OR 1.84), coughing (OR 2.61), and symptoms >=4 weeks
      (OR 1.66) were predictors of PTB concomitant with TBTB. About 59.7% TBTB patients
      developed tracheobronchial stenosis, of which 23.3% cases presented severe airway
      narrowing. Female sex (OR 2.27), age < 50 years (OR 2.11), shortness of breath
      (OR 1.97), and symptoms >=4 weeks (OR 1.71) were predictors of TBTB-related
      tracheobronchial stenosis. CONCLUSIONS: About 23.9% of PTB patients undergoing
      bronchoscopy present with TBTB in Guangdong province, southern China. Young and
      middle-aged females with symptoms persisting for >=4 weeks (the main predictors
      of TBTB and related tracheobronchial stenosis) should receive bronchoscopy
      immediately when diagnosed with PTB.

PMID- 30205410
TI  - Chronic Microcystin-LR Exposure Induces Hepatocarcinogenesis via Increased
      Gankyrin in Vitro and in Vivo.
AB  - BACKGROUND/AIMS: Our recent study indicated that the serum microcystin-LR (MC-LR)
      level is positively linked to the risk of human hepatocellular carcinoma (HCC).
      Gankyrin is over-expressed in cancers and mediates oncogenesis; however, whether
      MC-LR induces tumor formation and the role of gankyrin in this process is
      unclear. METHODS: We induced malignant transformation of L02 liver cells via 35
      passages with exposure to 1, 10, or 100 nM MC-LR. Wound healing, plate and soft
      agar colony counts, and nude mice tumor formation were used to evaluate the
      tumorigenic phenotype of MC-LR-treated cells. Silencing gankyrin was used to
      confirm its function. We established a 35-week MC-LR exposure rat model by twice
      weekly intraperitoneal injection with 10 MUg/kg body weight. In addition, 96 HCC
      patients were tested for tumor tissue gankyrin expression and serum MC-LR levels.
      RESULTS: Chronic low-dose MC-LR exposure increased proliferation, mobility, clone
      and tumor formation abilities of L02 cells as a result of gankyrin activation,
      while silencing gankyrin inhibited the carcinogenic phenotype of MC-LR-treated
      cells. MC-LR also induced neoplastic liver lesions in Sprague-Dawley rats due to
      up-regulated gankyrin. Furthermore, a trend of increased gankyrin was observed in
      humans exposed to MC-LR. CONCLUSION: These results suggest that MC-LR induces
      hepatocarcinogenesis in vitro and in vivo by increasing gankyrin levels,
      providing new insight into MC-LR carcinogenicity studies.

PMID- 30205413
TI  - Bilirubin Production Is Increased in Newborn Mice Exposed to Isoflurane.
AB  - BACKGROUND: Increased bilirubin production due to hemolysis can lead to severe
      neonatal hyperbilirubinemia and, if left untreated, to bilirubin neurotoxicity.
      Post-cardiac surgery newborns have been shown to be at an increased risk for
      developing hyperbilirubinemia and also hemolysis. Isoflurane (ISO), a volatile
      anesthetic agent routinely used in newborn surgery, has been reported to
      upregulate heme oxygenase 1 (HO-1) expression. HO is the rate-limiting enzyme in
      the bilirubin production pathway. OBJECTIVE: Here, we evaluated whether ISO
      exposure induces HO-1 and further increases bilirubin production in a hemolytic
      newborn mouse model. METHODS: Three-day-old newborn mice were exposed to 2% ISO
      for 18 min or air. Liver HO activity and HO-1 protein were measured after
      exposure to ISO. Next, we evaluated the effect of ISO exposure on bilirubin
      production as indexed by the total body excretion rate of carbon monoxide
      following heme loading. RESULTS: ISO significantly increased liver HO activity
      120% and 116% at 24 and 48 h, respectively, after exposure. HO-1 protein levels
      also similarly increased after ISO exposure, but the increases were not
      statistically significant compared with controls. After heme loading, ISO-exposed
      pups had significantly higher bilirubin production rates (1.24-fold), and also
      peaked earlier, than age-matched nonexposed pups. CONCLUSIONS: ISO exposure can
      induce HO-1 expression in the liver and may explain the development of severe
      hyperbilirubinemia in postsurgical infants, especially in those undergoing
      hemolysis.

PMID- 30205412
TI  - Epidemiological and Clinical Patterns of Kaposi Sarcoma: A 16-Year Retrospective
      Cross-Sectional Study from Yaounde, Cameroon.
AB  - BACKGROUND: The burden of Kaposi sarcoma (KS) is increasing fast among HIV
      infected populations, but the disease remains desperately underexplored in
      Cameroon, where the burden of HIV is high. METHODS: This is a retrospective cross
      sectional study carried out over a period of 16 years (January 2001 to December
      2016) at the HIV day care unit of the Central Hospital of Yaounde, Cameroon. The
      diagnosis was based on clinical aspects and histological confirmation, and we
      used a preconstructed questionnaire for data collection through patients'
      electronic and physical files. RESULTS: Among 14,220 files reviewed, 316 cases of
      KS were identified, yielding a cumulative incidence of 2.2%. In the end, 266
      patients (55% male) were included in this study. The patients' age ranged from 17
      to 72 years, with a mean of 37.8 +/- 9.5 years. KS was the presenting
      manifestation of HIV in 89.8% of the cases. Cutaneous lesions occurred more often
      (81.6%), mainly located on the lower limbs (47.7%); mucous lesions were found in
      15.8% of the patients, while 8 patients (3.0%) had associated visceral lesions.
      The lesions predominantly were lymphedemas (28.6%) and papulonodules (21.1%). At
      the diagnosis of KS, the median CD4 count was 175 cells/mm3 (interquartile range
      80.5-288.5), and 150 patients (56.6%) had CD4 counts < 200 cells/mm3.
      CONCLUSIONS: KS is frequent among our HIV-infected patients; it seems to occur
      most often at a younger adult age and represents one of the presenting
      manifestations of HIV/AIDS in our context. It seems to equally affect men and
      women, occurring more often when CD4 counts are < 200 cells/mm3.

PMID- 30205414
TI  - Validation of Raised Cord Blood Interleukin-16 in Perinatal Asphyxia and Neonatal
      Hypoxic-Ischaemic Encephalopathy in the BiHiVE2 Cohort.
AB  - The role of inflammation is an important factor in the progression of hypoxic
      ischaemic encephalopathy (HIE). We have previously shown that interleukin-16 (IL
      16) is increased in infants with moderate and severe HIE and relates to poor
      neurodevelopmental outcomes. We aimed to validate IL-16 as a cord blood-based
      biomarker for HIE and to examine its relationship to long-term outcomes. The
      study sample consisted of 105 full-term infants who experienced perinatal
      asphyxia (PA) (with and without an encephalopathy) along with healthy,
      gestational age-matched newborn controls. Umbilical cord blood serum was
      processed and biobanked at delivery. Infants were assigned a modified Sarnat
      score at 24 h. Analysis of IL-16 cytokine cord blood levels was performed using
      the sandwich-based enzyme-linked immunosorbent assay (ELISA) technique. Cord
      blood-based IL-16 was increased in infants with PA and HIE relative to controls
      (p = 0.025). IL-16 was also increased in the HIE group relative to controls (p =
      0.042). There was no significant difference in IL-16 across grades of HIE or in
      those with abnormal outcomes at 2 years of age. This study validates findings
      that cord blood-based IL-16 levels are increased in infants with PA, including
      those who go on to develop HIE.

PMID- 30205415
TI  - Association of Epicardial Fat Tissue with Coronary Artery Disease and Left
      Ventricle Diastolic Function Indicators.
AB  - BACKGROUND Epicardial fat tissue (EAT) acts as brown adipose tissue and protects
      the heart and coronary arteries against hypothermia. Recent studies demonstrated
      that EAT is a source of both anti-inflammatory and atherogenic cytokines. In this
      study, our aim was to investigate the association of vertical, horizontal, and
      area measurements of EAT thickness and their association with coronary artery
      disease, diastolic function, and myocardial performance index in patients who
      underwent coronary angiography. MATERIAL AND METHODS The study population
      consisted of patients who presented to our outpatient clinic with chest pain and
      whose non-invasive stress tests were positive between June 2015 and July 2017.
      Echocardiographic examinations were performed prior to the angiography. Coronary
      angiograms were performed using Judkins method from the femoral artery. RESULTS
      Mean vertical thickness of EAT was 0.6 cm in patients with CAD and 0.46 cm in
      those without CAD (p=0.0001). Mean horizontal length of EAT was 2.91 cm in
      patients with CAD and was 2.41 cm in the subjects without CAD (p=0.001). ROC
      analysis showed 81% sensitivity and 53% specificity for a cut-off value of 0.45,
      and 67% sensitivity and 71% specificity for a cut-off value of 0.55 for EAT
      vertical (cm). Multivariate analysis showed that EAT is an independent risk
      factor for coronary artery disease. CONCLUSIONS Echocardiography is an
      inexpensive routine assessment for most patients. EAT thickness determined by
      echocardiography may be a useful indicator of increased CAD risk, but not
      diastolic dysfunction, of the left ventricle.

PMID- 30205416
TI  - Comparative Effectiveness of Abdominal versus Laparoscopic Radical Hysterectomy
      for Cervical Cancer in the Postdissemination Era.
AB  - Purpose: Despite the benefits of minimally invasive surgery for cervical cancer,
      there are a lack of randomized trials comparing laparoscopic radical hysterectomy
      and abdominal radical hysterectomy. We compared morbidity, cost of care, and
      survival between abdominal radical hysterectomy and laparoscopic radical
      hysterectomy for cervical cancer. Materials and Methods: We used the Korean
      nationwide database to identify women with cervical cancer who underwent radical
      hysterectomy from January 1, 2011 to December 31, 2014. Patients who underwent
      abdominal radical hysterectomy were compared to those who underwent laparoscopic
      radical hysterectomy. Perioperative morbidity, the use of adjuvant therapy, and
      survival were evaluated after propensity score balancing. Results: We identified
      6,335 patients, including 3,235 who underwent abdominal radical hysterectomy and
      3,100 who underwent laparoscopic radical hysterectomy. The use of laparoscopic
      radical hysterectomy increased from 46.1% in 2011 to 51.8% in 2014. Patients who
      were younger, had a more recent year of diagnosis, and were treated in the
      metropolitan area were more likely to undergo a laparoscopic procedure (p<0.001).
      Compared to abdominal radical hysterectomy, laparoscopic radical hysterectomy was
      associated with lower rates of complication, fewer transfusions, a shorter
      hospital stay, less adjuvant therapy, and reduced total medical costs (p<0.001).
      Laparoscopic surgery was associated with a better overall survival than abdominal
      operation (hazard ratio=0.74; 95% confidence interval, 0.64 to 0.85). Conclusion:
      In the postdissemination era, laparoscopic radical hysterectomy was associated
      with more favorable morbidity profiles, a lower cost of care, and comparable
      survival than abdominal radical hysterectomy.

PMID- 30205417
TI  - Salvage Concurrent Chemo-radiation Therapy for Loco-regional Recurrence Following
      Curative Surgery of Non-small Cell Lung Cancer.
AB  - Purpose: This study is to report clinical outcomes of salvage concurrent chemo
      radiation therapy (CCRT) in treating patients with loco-regional recurrence (LRR)
      following initial complete resection of non-small cell lung cancer. Materials and
      Methods: Between February 2004 and December 2016, 127 patients underwent salvage
      CCRT for LRR. The median radiation therapy (RT) dose was 66 Gy and clinical
      target volume was to cover recurrent lesion with margin without elective
      inclusion of regional lymphatics. Majority of patients (94.5%) received weekly
      platinum-based doublet chemotherapy during RT course. Results: The median follow
      up time from the start of CCRT was 25 months. The median survival duration was 49
      months, and overall survival (OS) rates at 2- and 5-years were 72.9% and 43.9%.
      The 2- and 5-year rates of in-field failure-free survival, distant metastasis
      free survival and progression free survival were 82.4% and 73.8%, 50.4% and
      39.9%, and 34.6% and 22.3%, respectively. Grade >=3 radiation-related esophagitis
      and pneumonitis occurred in 14 (11.0%) and six patients (4.7%), respectively. On
      both univariate and multivariate analysis, higher biologically equivalent dose
      (BED)10 (>=79.2 Gy10 vs. <79.2 Gy10; HR, 0.431), smaller clinical target volume
      (CTV) (<=80 cm3 vs. >80 cm3; hazard ratio [HR], 0.403), and longer disease-free
      interval (>1 year vs. <=1 year; HR, 0.489) were significantly favorable factors
      for OS. Conclusion: The current study has demonstrated that high dose salvage
      CCRT focused to the involved lesion only was highly effective and safe. In
      particular, higher BED10, smaller CTV, and longer disease-free interval were
      favorable factors for improved survival.

PMID- 30205418
TI  - IgG4-Related Sclerosing Cholangitis and Primary Sclerosing Cholangitis.
AB  - Sclerosing cholangitis (SC) is defined as a condition with progressive stenosis
      and destruction of the bile ducts due to diffuse inflammation and fibrosis and
      currently includes three categories: primary sclerosing cholangitis (PSC),
      secondary cholangitis, and IgG4-related sclerosing cholangitis (IgG4-SC). SC
      categories share similar clinical features, such as cholestasis. Patients with SC
      present with cholestatic symptoms, including jaundice and pruritus, and blood
      tests reveal elevation of cholestatic enzymes. Cholangiography, endoscopic or
      magnetic, is inevitably required for making a diagnosis. Although the
      presentation of IgG4-SC and PSC are similar, the comorbidities, treatment
      response, and outcomes differ significantly, and therefore, it is strongly
      advisable to be familiar with these two diseases to make a correct diagnosis.
      Differentiation of cholangiocarcinoma from IgG4-SC and PSC is also extremely
      important. In this review, the clinical characteristics, comorbidities, treatment
      and outcomes of IgG4-SC and PSC will be outlined based on experience mainly from
      Japan.

PMID- 30205419
TI  - Corrigendum.

PMID- 30205420
TI  - Application of Laser Flare Photometry in the Quantification of Blood-Aqueous
      Barrier Breakdown after Micro-incision Vitrectomy.
AB  - PURPOSE: The purpose of the study is to quantify aqueous flare using laser flare
      photometry (LFM) in patients undergoing 25-G pars plana vitrectomy (PPV) and
      assess the need for postoperative topical corticosteroid administration .
      METHODS: Prospective evaluation of 50 eyes (50 patients) was performed using LFM
      until day 30 postoperative. Duration of surgery, indication of PPV, and use of
      laser and/or cryotherapy were noted. Topical corticosteroids were used if mean
      LFM values were >50, or if there was anterior chamber fibrin. RESULTS: Mean age
      of the subjects was 48.62 +/- 10.07 years. The preoperative LFM value for 50
      subjects was 17.42 +/- 25.20. Topical corticosteroids were initiated in only 22
      patients. The LFM values of subjects were not different from baseline at 1 month
      whether or not the subjects received corticosteroids (p > 0.106). CONCLUSIONS:
      With 25-G PPV, there is minimal breakdown of blood-aqueous barrier. LFM helps in
      monitoring postoperative inflammation, obviating the need for topical
      corticosteroids in significant number of patients.

PMID- 30205421
TI  - Evaluation of Noninvasive Prenatal Testing (NIPT) guidelines using the AGREE II
      instrument.
AB  - OBJECTIVE: The rapid increase of cell-free fetal DNA analysis for Down syndrome
      screening requires evidence-based clinical practice guidelines for noninvasive
      prenatal testing (NIPT). Several studies show that the quality of many guidelines
      is low and there are still many health areas where this quality is not
      systematically evaluated. Given the absence of research, in the NIPT field, we
      used an internationally validated tool to evaluate a set of three NIPT practice
      guidelines and to look at dimensions that can be improved. METHODS: Four
      appraisers, experts in prenatal screening, evaluated three main NIPT guidelines
      published in the last 2 years using the AGREE II (Appraisal of Guidelines for
      Research and Evaluation II), a tool specifically designed for guideline quality
      appraisal. RESULTS: Guidelines scored higher in domains related with scope,
      purpose, and clarity of presentation, and lower in stakeholder involvement and
      rigor of development. Intradomain items evaluation showed asymmetries between
      guidelines. The UK-NSC was the guideline with the best scores. DISCUSSION:
      Several areas of NIPT guidelines, such as stakeholders involvement, selection of
      supporting evidence, external reviews, updating processes, and competing
      interests disclosure, can be improved. Appraisers recommend modifications to all
      NIPT guidelines that can lead to substantial improvements in their methodological
      quality and subsequently make a contribution to prenatal screening improvement.

PMID- 30205422
TI  - Logical Inference Framework for Experimental Design for Mechanical
      Characterization Procedures.
AB  - Optimizing an experimental design is a complex task when a model is required for
      indirect reconstruction of physical parameters from the sensor readings. In this
      work, a formulation is proposed to unify the probabilistic reconstruction of
      mechanical parameters and an optimization problem. An information-theoretic
      framework combined with a new metric of information density is formulated
      providing several comparative advantages: (i) a straightforward way to extend the
      formulation to incorporate additional concurrent models, as well as new unknowns
      such as experimental design parameters in a probabilistic way; (ii) the model
      causality required by Bayes' theorem is overridden, allowing generalization of
      contingent models; and (iii) a simpler formulation that avoids the characteristic
      complex denominator of Bayes' theorem when reconstructing model parameters. The
      first step allows the solving of multiple-model reconstructions. Further
      extensions could be easily extracted, such as robust model reconstruction, or
      adding alternative dimensions to the problem to accommodate future needs.

PMID- 30205423
TI  - Elastic Properties and Electronic Properties of MxNy (M = Ti, Zr) from First
      Principles Calculations.
AB  - The elastic properties and electronic properties of MxNy (M = Ti, Zr) TiN, Ti2N,
      Zr3N4, ZrN with different structures have been investigated using density
      functional theory. Through the calculation of the elastic constants, it was found
      that all of these structures meet the mechanical stability except for ZrN with
      space group P63mc. Their mechanical properties are studied by a comparison of
      various parameters. The stiffness of TiN is larger than that of ZrN with space
      group Fm 3 - m. Ti2N's stiffness with space group I41/amdz is larger than Ti2N
      with space group P42/mnm. Zr3N4's stiffness with space group Pnam is largest in
      three structures of Zr3N4. TiN, Ti2N and ZrN are non-central force, Zr3N4 is
      central force. TiN and ZrN with space group Fm 3 - m are brittle, and TiN is
      brittler than ZrN with space group Fm 3 - m. The two kinds of Ti2N are brittle
      and Ti2N with space group I41/amdz is larger. Three structures of Zr3N4 are tough
      and Zr3N4 with space group I 4 - 3d is the toughest. Meanwhile, the electronic
      properties of TiN, Ti2N, Zr3N4 and ZrN were calculated, possible superconducting
      properties of the studied materials were predicted.

PMID- 30205424
TI  - Plasma Retinol Levels and High-Sensitivity C-Reactive Protein in Prepubertal
      Children.
AB  - The relationship between C-reactive protein (CRP) levels and plasma antioxidants
      has been established in adults. However, the association has been rarely
      investigated in healthy children. Thus, we examined the cross-sectional
      association of high-sensitivity CRP (hs-CRP) levels with fat-soluble plasma
      antioxidant concentrations in a cohort of healthy prepubertal children. We
      determined hs-CRP levels in 543 healthy six-eight-year-old children using a high
      sensitivity CRP enzyme-linked immuno sorbent assay (ELISA) kit. The plasma
      concentrations of lipids, apolipoproteins and lipid-soluble antioxidants (alpha
      tocopherol, gamma-tocopherol, lycopene, alpha-carotene, beta-carotene and
      retinol) were determined using standardized methods. Pearson correlation analysis
      showed significant correlations between plasma hs-CRP and alpha-carotene and
      retinol concentrations. After adjusting by sex, body mass index (BMI) and lipid
      levels, only the association with retinol remains significant, with children in
      the highest hs-CRP tertile group (hs-CRP >= 0.60 mg/dL) showing significantly
      lower levels of retinol than those from the tertiles 1 and 2. A stepwise linear
      regression selected retinol, BMI, apo A-I and sex as predictors of hs-CRP levels,
      in a model explaining 19.2% of the variability of hs-CRP. In conclusion, in
      healthy prepubertal children, after adjusting by sex, BMI and lipid levels, hs
      CRP concentrations were highly associated with plasma retinol, which is
      transported in blood bound to retinol-binding protein but were not associated
      with the lipoprotein-bound antioxidants.

PMID- 30205425
TI  - Possible Mechanisms of Green Tea and Its Constituents against Cancer.
AB  - A number of epidemiological, clinical, and experimental researches have indicated
      that administration of green tea appears to have anti-cancer activity. According
      to findings of laboratory cell culture studies, a diverse mechanism has been
      observed underlying the effects of green tea catechins against cancer. These
      mechanisms include anti-oxidant activity, cell cycle regulation, receptor
      tyrosine kinase pathway inhibition, immune system modulation, and epigenetic
      modification control. This review discusses the results of these studies to
      provide more insight into the effects of green tea administration on cancers
      observed to date in this research field.

PMID- 30205428
TI  - Spheroidization of Nickel Powder and Coating with Carbon Layer through Laser
      Heating.
AB  - We developed a simple and efficient process, laser heating of nickel powder in
      ethanol, to produce carbon-encapsulated nickel microspheres. Long-pulse-width
      laser heated nickel powder suspended in pure ethanol into liquid droplets. In
      turn, the latter droplets became sphere-like, pyrolyzed surrounding ethanol and
      dissolved the produced carbon atoms. Because of their lower solubility in solid
      nickel, excess carbon atoms were then expelled from the metal core after
      solidification, thus forming graphite-like shells on the laser-modified Ni
      spheres. Hence, after pyrolysis the transformation of carbon was found to follow
      the dissolution-precipitation mechanism. The produced carbon-encapsulated nickel
      microspheres exhibited higher oxidation resistance compared with the initial
      nickel powder, while keeping their magnetic properties essentially unchanged.

PMID- 30205426
TI  - Simultaneous Determination of Aesculin, Aesculetin, Fraxetin, Fraxin and
      Polydatin in Beagle Dog Plasma by UPLC-ESI-MS/MS and Its Application in a
      Pharmacokinetic Study after Oral Administration Extracts of Ledum palustre L.
AB  - A rapid, simple and sensitive ultra-performance liquid chromatography
      electrospray-ionization-tandem mass spectrometry (UPLC-ESI-MS/MS) method was
      developed and validated for the simultaneous determination of aesculin,
      aesculetin, fraxetin, fraxin and polydatin in beagle dog plasma for the first
      time. Plasma samples were pretreated by protein precipitation with methanol.
      Chromatographic separation was performed on an Acquity UPLC HSS T3 C18 column
      (2.1 mm * 100 mm, 1.8 MUm) with gradient elution at a flow rate of 0.4 mL/min,
      using a mobile phase consisting of 0.1% formic acid (A) and acetonitrile (B). The
      analytes and IS were detected by multiple reaction monitoring (MRM) via negative
      ion mode with ion transitions of m/z 339.1-m/z 176.8 for aesculin, m/z 176.8-m/z
      88.9 for aesculetin, m/z 206.8-m/z 192.1 for fraxetin, m/z 369.1-m/z 206.9 for
      fraxin, m/z 389.1-m/z 227.0 for polydatin and m/z 415.2-m/z 295.1 for puerarin.
      This method was validated according to the FDA guidelines and the results met the
      requirements of analysis. The calibration curves of analytes were linear with
      correlation coefficients more than 0.9980. The intra- and inter-day precisions
      were less than 15% and the accuracy was within +/-15%. The maximum plasma
      concentration (Cmax) of aesculin, aesculetin, fraxetin, fraxin and polydatin was
      46.75 +/- 7.46, 209.9 +/- 57.65, 369.7 +/- 48.87, 67.04 +/- 12.09 and 47.14 +/-
      12.04 ng/mL, respectively. The time to reach the maximum plasma concentration
      (Tmax) was 1.32 +/- 0.38 h for aesculin, 1.03 +/- 0.27 h for aesculetin, 0.94 +/-
      0.23 h for fraxetin, 0.83 +/- 0.18 h for fraxin and 1.15 +/- 0.15 h for
      polydatin. The results indicated that the absorption of aesculin might be slow in
      beagle dog plasma. This method was successfully applied for pharmacokinetics in
      beagle dog plasma after oral administration of the extracts of Ledum palustre L.
      at a dosage of 0.27 g/kg.

PMID- 30205427
TI  - Carnosine Supplementation Improves Serum Resistin Concentrations in Overweight or
      Obese Otherwise Healthy Adults: A Pilot Randomized Trial.
AB  - Adipokines play an important role in the regulation of glucose metabolism. We
      have previously shown that carnosine supplementation in overweight or obese non
      diabetic individuals improves glucose metabolism but does not change adiponectin
      concentrations. However, its effect on other adipokines has not been
      investigated. Herein we further determined the effect of carnosine
      supplementation on serum adipsin, resistin and leptin. Twenty-two overweight or
      obese otherwise healthy adults were randomly assigned to receive either 2 g of
      carnosine (n = 13) or identically looking placebo (n = 9) for 12 weeks. Serum
      adipsin, leptin and resistin were analyzed using a bead-based multiplex assay.
      Carnosine supplementation decreased serum resistin concentrations compared to
      placebo (mean change from baseline: -35 +/- 83 carnosine vs. 35 +/- 55 ng/mL
      placebo, p = 0.04). There was a trend for a reduction in serum leptin
      concentrations after carnosine supplementation (-76 +/- 165 ng/mL carnosine vs.
      20 +/- 28 ng/mL placebo, p = 0.06). The changes in leptin and resistin
      concentrations were inversely related to the change in concentration for urinary
      carnosine (r = -0.72, p = 0.0002; r = -0.67, p = 0.0009, respectively), carnosine
      propanal (r = -0.56, p = 0.005; r = -0.63, p = 0.001, respectively) and carnosine
      propanol (r = -0.61, p = 0.002; r = -0.60, p = 0.002, respectively). There were
      no differences between groups in change in adipsin concentrations. Our findings
      show carnosine supplementation may normalize some, but not all, of the serum
      adipokine concentrations involved in glucose metabolism, in overweight and obese
      individuals. Further clinical trials with larger samples are needed to confirm
      these results.

PMID- 30205430
TI  - New Anti-Inflammatory Aporphine and Lignan Derivatives from the Root Wood of
      Hernandia nymphaeifolia.
AB  - A new aporphine, 3-hydroxyhernandonine (1) and a new lignin, 4'-O-demethyl-7-O
      methyldehydropodophyllotoxin (2), have been isolated from the root wood of
      Hernanadia nymphaeifolia, together with thirteen known compounds (3-15). The
      structures of these compounds were determined through mass spectrometry (MS) and
      spectroscopic analyses. The known isolate, 2-O-methyl-7-oxolaetine (3), was first
      isolated from natural sources. Among the isolated compounds, 3
      hydroxyhernandonine (1), 4'-O-demethyl-7-O-methyldehydropodophyllotoxin (2),
      hernandonine (4), oxohernangerine (5), and oxohernagine (6) displayed inhibition
      (IC50 values <=5.72 MUg/mL) of superoxide anion production by human neutrophils
      in response to formyl-l-methionyl-l-leucyl-l-phenylalanine/cytochalasin B
      (fMLP/CB). In addition, 3-hydroxyhernandonine (1), 4'-O-demethyl-7-O
      methyldehydropodophyllotoxin (2), oxohernangerine (5), and oxohernagine (6)
      suppressed fMLP/CB-induced elastase release with IC50 values <=5.40 MUg/mL.

PMID- 30205429
TI  - Probiotics in the Treatment of Colorectal Cancer.
AB  - The human microbiome plays many roles in inflammation, drug metabolism, and even
      the development of cancer that we are only beginning to understand. Colorectal
      cancer has been a focus for study in this field as its pathogenesis and its
      response to treatment have both been linked to the functioning of microbiota.
      This literature review evaluates the animal and human studies that have explored
      this relationship. By manipulating the microbiome with interventions such as
      probiotic administration, we may be able to reduce colorectal cancer risk and
      improve the safety and effectiveness of cancer therapy even though additional
      clinical research is still necessary.

PMID- 30205431
TI  - Robotic Stereotactic Radiosurgery in Melanoma Patients with Brain Metastases
      under Simultaneous Anti-PD-1 Treatment.
AB  - Combination concepts of radiotherapy and immune checkpoint inhibition are
      currently of high interest. We examined imaging findings, acute toxicity, and
      local control in patients with melanoma brain metastases receiving programmed
      death 1 (PD-1) inhibitors and/or robotic stereotactic radiosurgery (SRS). Twenty
      six patients treated with SRS alone (n = 13; 20 lesions) or in combination with
      anti-PD-1 therapy (n = 13; 28 lesions) were analyzed. Lesion size was evaluated
      three and six months after SRS using a volumetric assessment based on cranial
      magnetic resonance imaging (cMRI) and acute toxicity after 12 weeks according to
      the Common Terminology Criteria for Adverse Events (CTCAE). Local control after
      six months was comparable (86%, SRS + anti-PD-1, and 80%, SRS). All toxicities
      reported were less than or equal to grade 2. One metastasis (5%) in the SRS group
      and six (21%) in the SRS + anti-PD-1 group increased after three months, whereas
      four (14%) of the six regressed during further follow-ups. This was rated as
      pseudoprogression (PsP). Three patients (23%) in the SRS + anti-PD-1 group showed
      characteristics of PsP. Treatment with SRS and anti-PD-1 antibodies can be
      combined safely in melanoma patients with cerebral metastases. Early volumetric
      progression of lesions under simultaneous treatment may be related to PsP; thus,
      the evaluation of combined radioimmunotherapy remains challenging and requires
      experienced teams.

PMID- 30205434
TI  - Effects of Static Heat and Dynamic Current on Al/Zn?Cu/Sn Solder/Ag Interfaces of
      Sn Photovoltaic Al-Ribbon Modules.
AB  - This present study applied Cu?Zn/Al ribbon in place of a traditional Cu ribbon to
      a photovoltaic (PV) ribbon. A hot-dipped and an electroplated Sn PV ribbon
      reflowed onto an Ag electrode on a Si solar cell and estimated the feasibility of
      the tested module (Ag/Solder/Cu?Zn/Al). After bias-aging, a bias-induced thermal
      diffusion and an electromigration promoted the growth of intermetallic compounds
      (IMCs) (Cu6Sn5, Ag3Sn). To simulate a photo-generated current in the series
      connection of solar cells, an electron with Ag-direction (electron flows from Ag
      to Al) and Al-direction (electron flows from Al to Ag) was passed through the
      Al/Zn?Cu/Solder/Ag structure to clarify the growth mechanism of IMCs. An increase
      in resistance of the Ag-direction-biased module was higher than that of the Al
      direction biased one due to the intense growth of Cu6Sn5 and Ag3Sn IMCs. The
      coated solder of the electroplated PV ribbon was less than that of the hot-dipped
      one, and thus decreased the growth reaction of IMCs and the cost of PV ribbon.

PMID- 30205433
TI  - Gas Leak Location Detection Based on Data Fusion with Time Difference of Arrival
      and Energy Decay Using an Ultrasonic Sensor Array.
AB  - Ultrasonic gas leak location technology is based on the detection of ultrasonic
      waves generated by the ejection of pressured gas from leak holes in sealed
      containers or pipes. To obtain more accurate leak location information and
      determine the locations of leak holes in three-dimensional space, this paper
      proposes an ultrasonic leak location approach based on multi-algorithm data
      fusion. With the help of a planar ultrasonic sensor array, the eigenvectors of
      two individual algorithms, i.e., the arrival distance difference, as determined
      from the time difference of arrival (TDOA) location algorithm, and the ratio of
      arrival distances from the energy decay (ED) location algorithm, are extracted
      and fused to calculate the three-dimensional coordinates of leak holes. The
      fusion is based on an extended Kalman filter, in which the results of the
      individual algorithms are seen as observation values. The final system state
      matrix is composed of distances between the measured leak hole and the sensors.
      Our experiments show that, under the condition in which the pressure in the
      measured container is 100 kPa, and the leak hole-sensor distance is 800 mm, the
      maximum error of the calculated results based on the data fusion location
      algorithm is less than 20 mm, and the combined accuracy is better than those of
      the individual location algorithms.

PMID- 30205435
TI  - Tribological Performance of Microhole-Textured Carbide Tool Filled with CaF2.
AB  - To enhance the friction and wear performance of cemented carbide, textured
      microholes were machined on micro Electron Discharge Machining (EDM) on the tool
      rake face, and Calcium Fluoride (CaF2) powders were burnished into the
      microholes. The friction and wear characteristics of the microhole-textured tool
      filled with CaF2 were investigated using sliding friction tests and dry cutting
      tests. Results exhibited that the working temperature could affect the
      tribological performance of the microhole-textured tool filled with CaF2 due to
      the temperature-sensitive nature of CaF2. There is no obvious lubrication effect
      for the textured tool filled with CaF2 at room temperature, while it was shown to
      be more effective in improving tribological property at a cutting speed of higher
      than 100 m/min with a corresponding to cutting temperature of 450  degrees C. The
      possible mechanisms for the microhole-textured tool filled with CaF2 were
      discussed and established.

PMID- 30205432
TI  - Proteomic Analysis of Rapeseed Root Response to Waterlogging Stress.
AB  - The overall health of a plant is constantly affected by the changing and hostile
      environment. Due to climate change and the farming pattern of rice (Oryza sativa)
      and rapeseed (Brassica napus L.), stress from waterlogging poses a serious threat
      to productivity assurance and the yield of rapeseed in China's Yangtze River
      basin. In order to improve our understanding of the complex mechanisms behind
      waterlogging stress and identify waterlogging-responsive proteins, we firstly
      conducted iTRAQ (isobaric tags for relative and absolute quantification)-based
      quantitative proteomic analysis of rapeseed roots under waterlogging treatments,
      for both a tolerant cultivar ZS9 and sensitive cultivar GH01. A total of 7736
      proteins were identified by iTRAQ, of which several hundred showed different
      expression levels, including 233, 365, and 326 after waterlogging stress for 4H,
      8H, and 12H in ZS9, respectively, and 143, 175, and 374 after waterlogging stress
      for 4H, 8H, and 12H in GH01, respectively. For proteins repeatedly identified at
      different time points, gene ontology (GO) cluster analysis suggested that the
      responsive proteins of the two cultivars were both enriched in the biological
      process of DNA-dependent transcription and the oxidation-reduction process, and
      response to various stress and hormone stimulus, while different distribution
      frequencies in the two cultivars was investigated. Moreover, overlap proteins
      with similar or opposite tendencies of fold change between ZS9 and GH01 were
      observed and clustered based on the different expression ratios, suggesting the
      two genotype cultivars exhibited diversiform molecular mechanisms or regulation
      pathways in their waterlogging stress response. The following qRT-PCR
      (quantitative real-time polymerase chain reaction) results verified the candidate
      proteins at transcription levels, which were prepared for further research. In
      conclusion, proteins detected in this study might perform different functions in
      waterlogging responses and would provide information conducive to better
      understanding adaptive mechanisms under environmental stresses.

PMID- 30205437
TI  - Future Spaces: Reinventing the Home Network for Better Security and Automation in
      the IoT Era.
AB  - Cyber-Physical Systems (CPSs) are complex systems comprising computation,
      physical, and networking assets. Used in various domains such as manufacturing,
      agriculture, vehicles, etc., they blend the control of the virtual and physical
      worlds. Smart homes are a peculiar type of CPS where the local networking
      fundamentals have seen little evolution in the past decades, while the context in
      which home networks operate has drastically evolved. With the advent of the
      Internet of Things (IoT), the number and diversity of devices connected to our
      home networks are exploding. Some of those devices are poorly secured and put
      users' data privacy and security at risk. At the same time, administrating a home
      network has remained a tedious chore, requiring skills from un-savvy users. We
      present Future Spaces, an end-to-end hardware-software prototype providing fine
      grained control over IoT connectivity to enable easy and secure management of
      smart homes. Relying on Software-Defined Networking-enabled home gateways and the
      virtualization of network functions in the cloud, we achieve advanced networking
      security and automation through the definition of isolated, usage-oriented
      slices. This disrupts how users discover, control and share their connected
      assets across multiple domains, smoothly adapting to various usage contexts.

PMID- 30205436
TI  - Resveratrol and Pterostilbene, Two Analogue Phenolic Compounds, Affect
      Aquaglyceroporin Expression in a Different Manner in Adipose Tissue.
AB  - Aquaglyceroporins (AQPs) are transmembrane channels that mediate glycerol release
      and glycerol uptake. They are involved in fat metabolism, with implications in
      obesity. The aim was to determine whether the administration of resveratrol and
      pterostilbene during the six weeks of the experimental period would modify AQPs
      expression in white and brown adipose tissues from Wistar rats fed an obesogenic
      diet, and to establish a potential relationship with the delipidating properties
      of these compounds. Consequently, thirty-six rats were divided into four groups:
      (a) group fed a standard diet; and three more groups fed a high-fat high-sucrose
      diet: (b) high-fat high-sucrose group: (c) pterostilbene-treated group (30
      mg/kg/d): (d) resveratrol-treated group (30 mg/kg/d). Epididymal, subcutaneous
      white adipose tissues and interscapular brown adipose tissue were dissected. AQPs
      gene expression (RT-PCR) and protein expression (western-blot) were measured. In
      white adipose tissue, pterostilbene reduced subcutaneous adipose tissue weight
      and prevented the decrease in AQP9 induced by obesogenic feeding, and thus
      glycerol uptake for triglyceride accumulation. Resveratrol reduced epididymal
      adipose tissue weight and avoided the decrease in AQPs related to glycerol
      release induced by high-fat high-sucrose feeding, suggesting the involvement of
      lipolysis in its body-fat lowering effect. Regarding brown adipose tissue, AQP7
      seemed not to be involved in the previously reported thermogenic activity of both
      phenolic compounds.

PMID- 30205438
TI  - Self-Cleaning Nanocomposite Membranes with Phosphorene-Based Pore Fillers for
      Water Treatment.
AB  - Phosphorene is a two-dimensional material exfoliated from bulk phosphorus and it
      possesses a band gap. Specifically, relevant to the field of membrane science,
      the band gap of phosphorene provides it with potential photocatalytic properties,
      which could be explored in making reactive membranes that can self-clean. The
      goal of this study was to develop an innovative and robust membrane that is able
      to control and reverse fouling with minimal changes in membrane performance. To
      this end, for the first time, membranes have been embedded with phosphorene.
      Membrane modification was verified by the presence of phosphorus on membranes,
      along with changes in surface charge, average pore size, and hydrophobicity.
      After modification, phosphorene-modified membranes were used to filter methylene
      blue (MB) under intermittent ultraviolet light irradiation. Phosphorene-modified
      and unmodified membranes displayed similar rejection of MB; however, after
      reverse-flow filtration was performed to mimic pure water cleaning, the average
      recovered flux of phosphorene-modified membranes was four times higher than that
      of unmodified membranes. Furthermore, coverage of MB on phosphorene membranes
      after reverse-flow filtration was four times lower than that of unmodified
      membranes, which supports the hypothesis that phosphorene membranes operated
      under intermittent ultraviolet irradiation can become self-cleaning.

PMID- 30205439
TI  - The Synergistic Effects of Orthokeratology and Atropine in Slowing the
      Progression of Myopia.
AB  - Atropine and orthokeratology (OK) are both effective in slowing the progression
      of myopia. In the current study, we studied the combined effects of atropine and
      OK lenses on slowing the progression of myopia. This retrospective study included
      84 patients who wore OK lenses and received atropine treatment (OA) and 95
      patients who wore OK lenses alone (OK) for 2 years. We stratified patients into
      low (<6 D, LM) and high (>=6 D, HM) myopia groups, as well as two different
      atropine concentrations (0.125% and 0.025%). Significantly better LM control was
      observed in OA1 patients, compared with OK1 patients. Axial length was
      significantly shorter in the OA1 group (24.67 +/- 1.53 mm) than in the OK1 group
      (24.9 +/- 1.98 mm) (p = 0.042); similarly, it was shorter in the OA2 group (24.73
      +/- 1.53 mm) than in the OK2 group (25.01 +/- 1.26 mm) (p = 0.031). For the HM
      patients, OA3 patients compared with OK3 patients, axial length was significantly
      shorter in the OA3 group (25.78 +/- 1.46 mm) than in the OK3 group (25.93 +/-
      1.94 mm) (p = 0.021); similarly, it was shorter in the OA4 patients (25.86 +/-
      1.21 mm) than in the OK4 patients (26.05 +/- 1.57 mm) (p = 0.011). Combined
      treatment with atropine and OK lenses would be a choice of treatment to control
      the development of myopia.

PMID- 30205440
TI  - Co-Production of Cellulose Nanocrystals and Fermentable Sugars Assisted by
      Endoglucanase Treatment of Wood Pulp.
AB  - In this study, fermentable sugars and cellulose nanocrystals (CNCs) were co
      produced from endoglucanase treatment of wood pulp, followed by acid hydrolysis.
      Enzymatic hydrolysis was performed using two endoglucanases differentiated by the
      presence or absence of a cellulose-binding domain (CBD). The enzyme with an
      intact CBD gave the higher glucan conversion (up to 14.1 +/- 1.2 wt %) and
      improved the degree of crystallinity of the recovered wood pulp fiber (up to 83.0
      +/- 1.0%). Thus, this endoglucanase-assisted treatment successfully removed
      amorphous content from the original cellulosic feedstock. CNC recovery (16.9 +/-
      0.7 wt %) from the feedstock going into the acid hydrolysis was improved relative
      to untreated pulp (13.2 +/- 0.6 wt %). The mass loss from enzymatic treatment did
      not cause a decrease in the CNC yield from the starting material. The
      characteristics of CNCs obtained through acid hydrolysis (with or without enzyme
      treatment of pulp) were analyzed using X-ray diffraction, transmission electron
      microscopy, dynamic light scattering, Fourier transform infrared spectroscopy,
      and differential scanning calorimetry as characterization techniques. The CNCs
      generated through acid hydrolysis of endoglucanase-treated wood pulp displayed
      comparable properties relative to those generated using untreated pulp. Thus,
      endoglucanase treatment can enable co-production of CNCs and sugars for biofuel
      fermentation.

PMID- 30205442
TI  - Effect of Thermal Vacancy on Thermodynamic Behaviors in BCC W Close to Melting
      Point: A Thermodynamic Study.
AB  - As temperature increases, the thermal vacancy concentration in pure metals
      dramatically increases and causes some strongly non-linear thermodynamic
      behaviors in pure metals when close to their melting points. In this paper, we
      chose body-centered cubic (bcc) W as the target and presented a thermodynamic
      model to account for its Gibbs energy of pure bcc W from 0 K to melting point by
      including the contribution of thermal vacancy. A new formula for interaction part
      was proposed for describing the quadratic temperature behavior of vacancy
      formation energy. Based on the experimental/first-principles computed
      thermodynamic properties, all the parameters in the Gibbs energy function were
      assessed by following the proposed two-step optimization strategy. The
      thermodynamic behaviors, i.e., the strong nonlinear increase for temperature
      dependence of heat capacities at high temperatures and a nonlinear Arrhenius plot
      of vacancy concentration, in bcc W can be well reproduced by the obtained Gibbs
      energy. The successful description of thermal vacancy on such strongly non-linear
      thermodynamic behaviors in bcc W indicates that the presently proposed
      thermodynamic model and optimization strategy should be universal ones and are
      applicable to all other metals.

PMID- 30205441
TI  - Sepsis: Personalized Medicine Utilizing 'Omic' Technologies-A Paradigm Shift?
AB  - Sepsis has over the years proven a considerable challenge to physicians and
      researchers. Numerous pharmacological and non-pharmacological interventions have
      been tested in trials, but have unfortunately failed to improve the general
      prognosis. This has led to the speculation that the sepsis population may be too
      heterogeneous to be targeted with the traditional one treatment suits all'
      approach. Recent advances in genetic and biochemical analyses now allow
      genotyping and biochemical characterisation of large groups of patients via the
      'omics' technologies. These new opportunities could lead to a paradigm shift in
      the approach to sepsis towards personalised treatments with interventions
      targeted towards specific pathophysiological mechanisms activated in the patient.
      In this article, we review the potentials and pitfalls of using new advanced
      technologies to deepen our understanding of the clinical syndrome of sepsis.

PMID- 30205443
TI  - Mode-Splitting for Refractive Index Sensing in Fluorescent Whispering Gallery
      Mode Microspheres with Broken Symmetry.
AB  - Whispering gallery mode (WGM) resonators have become increasingly diverse in
      terms of both architecture and applications, especially as refractometric
      sensors, allowing for unprecedented levels of sensitivity. However, like every
      refractometric sensor, a single WGM resonator cannot distinguish temperature
      variations from changes in the refractive index of the surrounding environment.
      Here, we investigate how breaking the symmetry of an otherwise perfect
      fluorescent microsphere, by covering half of the resonator with a high-refractive
      index (RI) glue, might enable discrimination of changes in temperature from
      variations in the surrounding refractive index. This novel approach takes
      advantage of the difference of optical pathway experienced by WGMs circulating in
      different equatorial planes of a single microsphere resonator, which induces mode
      splitting. We investigated the influence of the surrounding RI of the microsphere
      on mode-splitting through an evaluation of the sphere's WGM spectrum and quality
      factor (Q-factor). Our results reveal that the magnitude of the mode-splitting
      increases as the refractive index contrast between the high-refractive-index (RI)
      glue and the surrounding environment increases, and that when they are equal no
      mode-splitting can be seen. Investigating the refractive index sensitivity of the
      individual sub modes resulting from the mode-splitting unveils a new methodology
      for RI sensing, and enables discrimination between surrounding refractive index
      changes and temperature changes, although it comes at the cost of an overall
      reduced refractive index sensitivity.

PMID- 30205444
TI  - Effect of Magnetized Water on the Mechanical and Durability Properties of
      Concrete Block Pavers.
AB  - In this research, the effect of magnetized water on the mechanical and durability
      behavior of concrete block pavers was investigated. For this purpose, a total of
      five mixes were prepared with water that passed through a permanent magnetic
      field 10, 20, 40, and 80 times at a constant speed of 2.25 m/s. Compressive
      strength, splitting tensile strength, flexural strength, resistance to sulfuric
      acid attack, water absorption tests, and Scanning Electron Microscopy (SEM)
      analyses were conducted. The compressive strength, splitting tensile strength,
      and flexural strength test results showed a significant positive effect of using
      magnetized water. The remaining tests also revealed that using magnetized water
      increases the resistance of concrete block pavers to sulfuric acid attack and
      decreases their water absorption.

PMID- 30205446
TI  - Methodology to Reduce Distortion Using a Hybrid Thermal Welding Process.
AB  - Welding is a thermal process which results in high strain and stress values in
      the material and leads to its change of phase. This might cause significant
      distortions in the welded structure, which often becomes a relevant design and
      manufacturing issue. This study deals with a line-heating-based forming process
      that is applied at the moment of the welding operation, with the final objective
      of minimizing distortion. A FEM (finite element method) based on a thermo
      elastoplastic approach is used here. The computational method is first calibrated
      in three stages: heatline forming calibration, flame heat source calibration, and
      the weld process. The final model presented in this work simulates a hybrid
      process called htTTT (high-temperature thermal transient tensioning) which was
      optimized over large T welds to minimize the final distortion of the components.

PMID- 30205445
TI  - The Effect of Nordic Walking Training Combined with Vitamin D Supplementation on
      Postural Control and Muscle Strength in Elderly People-A Randomized Controlled
      Trial.
AB  - Nordic Walking (NW) and Vitamin D concentration (Vit D) alone have been shown to
      contribute to the health and performance of elderly people. However, the
      interaction between these two factors has yet to be explored. In this study 42
      women over 60 years of age (69.02 +/- 5.56 years) were recruited and divided in
      two NW groups: a high-intensity interval training group (HI-NW) and a moderate
      intensity continuous training group (MI-NW). Individuals from each group
      completed a 12-week NW training program (3 times a week/2 hours) combined with
      randomized Vitamin D supplementation (HD = high dose: 4000 IU/day or LD = low
      dose: 800 IU/day). Body composition, postural control, muscle strength and
      Vitamin D serum concentration were measured twice; before and after the
      intervention. To investigate the interaction between supplementation and training
      a mixed-design analysis of variance (ANOVA) was performed. The HI-NW group,
      regardless of supplementation dose, increased their Vit D and elbow torque
      performance. On the other hand, in the MI-NW group the same Vit D outcome was
      seen only with HD supplementation and was also associated with increased leg
      muscle mass. In conclusion, beneficial effects of both HI-NW and MI-NW training
      regimes were seen. The impact of the dose supplementation on Vit D and body
      composition was related to the type of NW training.

PMID- 30205447
TI  - Micro-Tensile Behavior of Mg-Al-Zn Alloy Processed by Equal Channel Angular
      Pressing (ECAP).
AB  - Commercially available AZ31 magnesium alloy was four times extruded in an equal
      rectangular channel using three different routes (A, B, and C). Micro tensile
      deformation tests were performed at room temperature with the aim to reveal any
      plastic anisotropy developed during the extrusion. Samples for micro tensile
      experiments were cut from extruded billets in different orientations with respect
      to the pressing direction. Information about the microstructure of samples was
      obtained using the electron back-scatter diffraction (EBSD) technique.
      Deformation characteristics (yield stress, ultimate tensile stress and uniform
      elongation) exhibited significant anisotropy as a consequence of different
      orientations between the stress direction and texture and thus different
      deformation mechanisms.

PMID- 30205449
TI  - Beyond the Literal Meaning of Words in Children with Klinefelter Syndrome: Two
      Case Studies.
AB  - Literature on children with Klinefelter Syndrome (KS) points to general
      linguistic difficulties in both comprehension and production among other
      cognitive functions, and in the majority of cases, these coexist with an
      intellectual level within the norms. In these conditions, children having
      language delay generally engage in language therapy and are systematically
      monitored across ages. In this article, we present the profiles of two children
      with KS (47, XXY), aged 9.1 (Child S) and 13 (Child D), whose language
      development was assessed as adequate at age 3, and for this reason, did not
      receive any language treatment. At the present stage, their IQ, as measured by
      Wechsler Scales (Child S: 92; Child D: 101), is within the norm, but they both
      present marked weaknesses in pragmatic skills such as figurative language
      comprehension. The analysis of these two cases points to the need to go beyond
      global indexes of verbal abilities, as the same global index may mask a wide
      diversification of individual profiles. In addition, this study underlines the
      importance of monitoring the developmental trajectories of children like Child D
      and Child S, because weaknesses in pragmatic skills that are relevant for both
      academic achievement and social adaptation could emerge at later stages.

PMID- 30205448
TI  - Proteomics Analysis Reveals Non-Controlled Activation of Photosynthesis and
      Protein Synthesis in a Rice npp1 Mutant under High Temperature and Elevated CO2
      Conditions.
AB  - Rice nucleotide pyrophosphatase/phosphodiesterase 1 (NPP1) catalyzes the
      hydrolytic breakdown of the pyrophosphate and phosphodiester bonds of a number of
      nucleotides including ADP-glucose and ATP. Under high temperature and elevated
      CO2 conditions (HT + ECO2), the npp1 knockout rice mutant displayed rapid growth
      and high starch content phenotypes, indicating that NPP1 exerts a negative effect
      on starch accumulation and growth. To gain further insight into the mechanisms
      involved in the NPP1 downregulation induced starch overaccumulation, in this
      study we conducted photosynthesis, leaf proteomic, and chloroplast
      phosphoproteomic analyses of wild-type (WT) and npp1 plants cultured under HT +
      ECO2. Photosynthesis in npp1 leaves was significantly higher than in WT.
      Additionally, npp1 leaves accumulated higher levels of sucrose than WT. The
      proteomic analyses revealed upregulation of proteins related to carbohydrate
      metabolism and the protein synthesis system in npp1 plants. Further, our data
      indicate the induction of 14-3-3 proteins in npp1 plants. Our finding
      demonstrates a higher level of protein phosphorylation in npp1 chloroplasts,
      which may play an important role in carbohydrate accumulation. Together, these
      results offer novel targets and provide additional insights into carbohydrate
      metabolism regulation under ambient and adverse conditions.

PMID- 30205450
TI  - Role of Homologous Recombination Genes in Repair of Alkylation Base Damage by
      Candida albicans.
AB  - Candida albicans mutants deficient in homologous recombination (HR) are extremely
      sensitive to the alkylating agent methyl-methane-sulfonate (MMS). Here, we have
      investigated the role of HR genes in the protection and repair of C. albicans
      chromosomes by taking advantage of the heat-labile property (55  degrees C) of
      MMS-induced base damage. Acute MMS treatments of cycling cells caused chromosome
      fragmentation in vitro (55  degrees C) due to the generation of heat-dependent
      breaks (HDBs), but not in vivo (30  degrees C). Following removal of MMS wild
      type, cells regained the chromosome ladder regardless of whether they were
      transferred to yeast extract/peptone/dextrose (YPD) or to phosphate buffer saline
      (PBS); however, repair of HDB/chromosome restitution was faster in YPD,
      suggesting that it was accelerated by metabolic energy and further fueled by the
      subsequent overgrowth of survivors. Compared to wild type CAI4, chromosome
      restitution in YPD was not altered in a Carad59 isogenic derivative, whereas it
      was significantly delayed in Carad51 and Carad52 counterparts. However, when post
      MMS incubation took place in PBS, chromosome restitution in wild type and HR
      mutants occurred with similar kinetics, suggesting that the exquisite sensitivity
      of Carad51 and Carad52 mutants to MMS is due to defective fork restart. Overall,
      our results demonstrate that repair of HDBs by resting cells of C. albicans is
      rather independent of CaRad51, CaRad52, and CaRad59, suggesting that it occurs
      mainly by base excision repair (BER).

PMID- 30205451
TI  - 29Si NMR Chemical Shifts in Crystalline and Amorphous Silicon Nitrides.
AB  - We investigate 29Si nuclear magnetic resonance (NMR) chemical shifts, deltaiso,
      of silicon nitride. Our goal is to relate the local structure to the NMR signal
      and, thus, provide the means to extract more information from the experimental
      29Si NMR spectra in this family of compounds. We apply structural modeling and
      the gauge-included projector augmented wave (GIPAW) method within density
      functional theory (DFT) calculations. Our models comprise known and hypothetical
      crystalline Si3N4, as well as amorphous Si3N4 structures. We find good agreement
      with available experimental 29Si NMR data for tetrahedral Si[4] and octahedral
      Si[6] in crystalline Si3N4, predict the chemical shift of a trigonal-bipyramidal
      Si[5] to be about -120 ppm, and quantify the impact of Si-N bond lengths on 29Si
      deltaiso. We show through computations that experimental 29Si NMR data indicates
      that silicon dicarbodiimide, Si(NCN)2 exhibits bent Si-N-C units with angles of
      about 143 degrees  in its structure. A detailed investigation of amorphous
      silicon nitride shows that an observed peak asymmetry relates to the proximity of
      a fifth N neighbor in non-bonding distance between 2.5 and 2.8 A to Si. We reveal
      the impact of both Si-N(H)-Si bond angle and Si-N bond length on 29Si deltaiso in
      hydrogenated silicon nitride structure, silicon diimide Si(NH)2.

PMID- 30205452
TI  - Antibody Light Chains Dictate the Specificity of Contact Hypersensitivity
      Effector Cell Suppression Mediated by Exosomes.
AB  - Antibody light chains (LCs), formerly considered a waste product of
      immunoglobulin synthesis, are currently recognized as important players in the
      activation of the immune response. However, very little is known about the
      possible immune regulatory functions of LCs. Recently, we reported that hapten
      specific LCs coat miRNA-150-carrying exosomes produced by CD8+ suppressor T cells
      downregulating the contact hypersensitivity (CHS) reaction in an antigen-specific
      manner, in mice tolerized by intravenous administration of a high dose of hapten
      coupled syngeneic erythrocytes. Thus, the current studies aimed at investigating
      the role of hapten-specific LCs in antigen-specific, exosome-mediated suppression
      of CHS effector cells. Suppressor T cell-derived exosomes from tolerized B-cell
      deficient uMT-/-, NKT-cell-deficient Jalpha18-/-, and immunoglobulin-deficient JH
      /- mice were nonsuppressive, unless supplemented with LCs of specificity strictly
      respective to the hapten used for sensitization and CHS elicitation in mice.
      Thus, these observations demonstrate that B1-cell-derived LCs, coating exosomes
      in vivo and in vitro, actually ensure the specificity of CHS suppression. Our
      research findings substantially expand current understanding of the newly
      discovered, suppressor T cell-dependent tolerance mechanism by uncovering the
      function of antigen-specific LCs in exosome-mediated, cell-cell communication.
      This express great translational potential in designing nanocarriers for specific
      targeting of desired cells.

PMID- 30205455
TI  - Health Consciousness and Its Effect on Perceived Knowledge, and Belief in the
      Purchase Intent of Liquid Milk: Consumer Insights from an Emerging Market.
AB  - This study is based on the influence of consumers' health consciousness (HC),
      perceived knowledge (PK) and beliefs affecting the attitude and purchase intent
      (PI) of the consumers. The outcome of this study is obtained through an exclusive
      survey conducted on a randomly selected sample of 712 households who purchase
      liquid milk (LM) in the cities of Dhaka and Chittagong in Bangladesh. A
      structured questionnaire is used to interview these participants to obtain data
      which are analysed employing descriptive statistics, Confirmatory Factor
      Analysis, and Structural Equation Modelling. The results of the analyses
      corroborate that consumers' health consciousness has a positive impact on
      perceived knowledge, belief, and attitude, but not on purchase intent. In
      addition, belief affects both the attitude and PI positively. Although consumers'
      perceived knowledge is too low to constitute their attitude towards LM, it has a
      positive, significant impact on the PI. The results also reveal that more than a
      third of the respondents consume LM several times per month, followed by more
      than a quarter of the sampled respondents who consume LM several times per week,
      and these consumption patterns have a positive and significant influence on the
      PI. Moreover, the monthly income of the family, age, and labelling preference are
      significantly correlated with PI.

PMID- 30205453
TI  - ACEI-Inhibitory Peptides Naturally Generated in Meat and Meat Products and Their
      Health Relevance.
AB  - Meat and meat products have been described as a very good source of angiotensin I
      converting enzyme (ACEI)-inhibitory peptides. The generation of bioactive
      peptides can occur through the action of endogenous muscular enzymes during
      processing, gastrointestinal digestion, or by using commercial enzymes in
      laboratory or industry under controlled conditions. Studies of bioavailability
      are necessary in order to prove the positive health effect of bioactive peptides
      in the body as they should resist gastrointestinal digestion, cross the
      intestinal barrier, and reach blood stream and target organs. However, in order
      to better understand their effect, interactions, and bioavailability, it is
      necessary to consider food matrix interactions and continue the development of
      quantitative methodologies in order to obtain more data that will enable advances
      in the field of bioactive peptides and the determination of their influence on
      health.

PMID- 30205454
TI  - Pharmacokinetic and Pharmacodynamic Properties of Rosmarinic Acid in Rat
      Cholestatic Liver Injury.
AB  - The objective of this study was to evaluate the hepatoprotective and metabolic
      effects of rosmarinic acid (RA) in rats. RA [100 mg/kg body weight (BW)] was
      intragastrically (i.g.) administered to Sprague-Dawley (SD) rats once a day for
      seven consecutive days. The rats were then i.g. administered alpha
      naphthylisothiocyanate (ANIT) (80 mg/kg once on the 5th day) to induce acute
      intrahepatic cholestasis after the last administration of RA. Blood samples were
      collected at different time points (0.083 h, 0.17 h, 0.33 h, 0.5 h, 0.75 h, 1 h,
      1.5 h, 3 h, 4 h, 6 h, 8 h, 12 h, 20 h) after administration, and the levels of RA
      were estimated by HPLC. Plasma and bile biochemical analysis, bile flow rate, and
      liver histopathology were measured to evaluate the hepatoprotective effect of RA.
      The PK-PD curves showed obviously clockwise (AST and ALT) or anticlockwise (TBA,
      TBIL). Pretreatment with RA at different doses significantly restrained ANIT
      induced pathological changes in bile rate, TBA, TBIL, ALT, AST (p < 0.05 or p <
      0.01). The relationship between RA concentration and its hepatoprotective effects
      on acute cholestasis responses was assessed by PK-PD modeling.

PMID- 30205456
TI  - White-Tailed Sea Eagle (Haliaeetus albicilla) Die-Off Due to Infection with
      Highly Pathogenic Avian Influenza Virus, Subtype H5N8, in Germany.
AB  - In contrast to previous incursions of highly pathogenic avian influenza (HPAIV)
      H5 viruses, H5N8 clade 2.3.4.4b viruses caused numerous cases of lethal
      infections in white-tailed sea eagles (Haliaeetus albicilla) affecting mainly
      young eagles (younger than five years of age) in Germany during winter 2016/2017.
      Until April 2017, 17 HPAIV H5N8-positive white-tailed sea eagles had been
      detected (three found alive and 14 carcasses) by real-time RT-PCR and partial
      nucleotide sequence analyses. Severe neurological clinical signs were noticed
      which were corroborated by immunohistopathology revealing mild to moderate, oligo
      to multifocal necrotizing virus-induced polioencephalitis. Lethal lead (Pb)
      concentrations, a main factor of mortality in sea eagles in previous years, could
      be ruled out by atomic absorption spectrometry. HPAIV H5 clade 2.3.4.4b
      reportedly is the first highly pathogenic influenza virus known to induce fatal
      disease in European white-tailed see eagles. This virus strain may become a new
      health threat to a highly protected species across its distribution range in
      Eurasia. Positive cloacal swabs suggest that eagles can spread the virus with
      their faeces.

PMID- 30205457
TI  - Work Related Stress, Well-Being and Cardiovascular Risk among Flight Logistic
      Workers: An Observational Study.
AB  - Work-related stress is a known occupational hazard, with a putative role on the
      development of cardiovascular diseases (CVD). Although several investigations
      have explored the association in various workplace scenarios, none have focused
      on the airport flight logistic support personnel, a transportation business of
      crucial importance, potentially exposed to job stress and consequently to an
      increase in CVD risk. We explored the relationship between work-related stress
      and cardiovascular risk in 568 healthy workers of a flight logistic support
      company using the Health and Safety Executive questionnaire, the Framingham Heart
      Study General Cardiovascular Disease (CVD) Risk Prediction Score, and the WHO
      general well-being index (WHO-5). We used univariate and multivariate statistical
      methods to take account of possible confounders. Our results show that a low job
      support significantly increases the CVD risk score and decreases the WHO well
      being index with reference to subjects reporting high support on the job. In
      addition, the well-being index of workers with high strain jobs appears lower in
      respect to workers employed in low strain job. The multivariate analysis confirms
      a protective effect of job support, and shows a detrimental influence on CVD risk
      by physical inactivity, regular intake of alcohol, and a low educational level.
      In addition, job control, job support, low strain, and high demand coupled with
      high control (active job) showed a beneficial effect on psychological well-being.
      Our results suggest that a combination of general risk factors and organizational
      factors contributes to increase CVD risk and well-being, representing a crucial
      target for intervention strategies to promote health in the workplace.

PMID- 30205458
TI  - Unusually Small Thermal Expansion of Ordered Perovskite Oxide CaCu3Ru4O12 with
      High Conductivity.
AB  - We measured the coefficient of thermal expansion (CTE) of conducting composite
      ceramics 30 vol.% CuO-mixed CaCu3Ru4O12 together with CaCu3Ru4O12 and CuO.
      Although conducting ceramics tend to show higher CTE values than insulators, and
      its CTE value does not match with other ceramic materials, the CTE of CaCu3Ru4O12
      (7-9 * 10-6/K) was as small as those of insulators such as CuO (9 * 10-6/K),
      alumina (8 * 10-6/K), and other insulating perovskite oxides. We propose that the
      thermal expansion of CaCu3Ru4O12 was suppressed by the Cu-O bond at the A-site
      due to the Jahn-Teller effect. This unusually small CTE of CaCu3Ru4O12 compared
      to other conducting oxides plays a vital role enabling successful coating of 30
      vol.% CuO-mixed CaCu3Ru4O12 thick films on alumina substrates, as demonstrated in
      our previous study.

PMID- 30205460
TI  - Epigenetic Control of Pancreatic Regeneration in Diabetes.
AB  - Both type 1 and type 2 diabetes are conditions that are associated with the loss
      of insulin-producing beta-cells within the pancreas. An active research therefore
      aims at regenerating these beta-cells with the hope that they could restore
      euglycemia. The approaches classically used consist in mimicking embryonic
      development, making use of diverse cell sources or converting pre-existing
      pancreatic cells. Despite impressive progresses and promising successes, it
      appears that we still need to gain further insight into the molecular mechanisms
      underlying beta-cell development. This becomes even more obvious with the
      emergence of a relatively new field of research, epigenetics. The current review
      therefore focuses on the latest advances in this field in the context of beta
      cell (neo-)genesis research.

PMID- 30205459
TI  - The Bisindole Alkaloid Caulerpin, from Seaweeds of the Genus Caulerpa, Attenuated
      Colon Damage in Murine Colitis Model.
AB  - Caulerpin (CLP), an alkaloid from algae of the genus Caulerpa, has shown anti
      inflammatory activity. Therefore, this study aimed to analyze the effect of CLP
      in the murine model of peritonitis and ulcerative colitis. Firstly, the mice were
      submitted to peritonitis to evaluate which dose of CLP (40, 4, or 0.4 mg/kg)
      could decrease the inflammatory infiltration in the peritoneum. The most
      effective doses were 40 and 4 mg/kg. Then, C57BL/6 mice were submitted to colitis
      development with 3% dextran sulfate sodium (DSS) and treated with CLP at doses of
      40 and 4 mg/kg. The disease development was analyzed through the disease activity
      index (DAI); furthermore, colonic tissue samples were submitted to histological
      analysis, NFkappaB determination, and in vitro culture for cytokines assay.
      Therefore, CLP at 4 mg/kg presented the best results, triggering improvement of
      DAI and attenuating the colon shortening and damage. This dose was able to reduce
      the TNF-alpha, IFN-gamma, IL-6, IL-17, and NFkappaB p65 levels, and increased the
      levels of IL-10 in the colon tissue. Thus, CLP mice treatment at a dose of 4
      mg/kg showed promising results in ameliorating the damage observed in the
      ulcerative colitis.

PMID- 30205461
TI  - Cardiac Rehabilitation Models around the Globe.
AB  - Alternative models of cardiac rehabilitation (CR) delivery, such as home or
      community-based programs, have been developed to overcome underutilization.
      However, their availability and characteristics have never been assessed
      globally. In this cross-sectional study, a piloted survey was administered online
      to CR programs globally. CR was available in 111/203 (54.7%) countries globally;
      data were collected in 93 (83.8% country response rate). 1082 surveys (32.1%
      program response rate) were initiated. Globally, 85 (76.6%) countries with CR
      offered supervised programs, and 51 (45.9%; or 25.1% of all countries) offered
      some alternative model. Thirty-eight (34.2%) countries with CR offered home-based
      programs, with 106 (63.9%) programs offering some form of electronic CR (eCR).
      Twenty-five (22.5%) countries with CR offered community-based programs. Where
      available, programs served a mean of 21.4% +/- 22.8% of their patients in home
      based programs. The median dose for home-based CR was 3 sessions (Q25-Q75 = 1.0
      4.0) and for community-based programs was 20 (Q25-Q75 = 9.6-36.0). Seventy-eight
      (47.0%) respondents did not perceive they had sufficient capacity to meet demand
      in their home-based program, for reasons including funding and insufficient
      staff. Where alternative CR models are offered, capacity is insufficient half the
      time. Home-based CR dose is insufficient to achieve health benefits. Allocation
      to program model should be evidence-based.

PMID- 30205463
TI  - Nonlinear Granger Causality between Health Care Expenditure and Economic Growth
      in the OECD and Major Developing Countries.
AB  - Differing from previous studies ignoring the nonlinear features, this study
      employs both the linear and nonlinear Granger causality tests to examine the
      complex causal relationship between health care expenditure and economic growth
      among 15 Organisation for Economic Co-operation and Development (OECD) and 5
      major developing countries. Some interesting findings can be obtained as follows:
      (1) For Australia, Austria, and UK, linear and nonlinear Granger causality does
      not exist between them. A unidirectional linear or nonlinear causality running
      from economic growth to health care expenditure can be found for Ireland, Korea,
      Portugal, and India. For these seven countries, health or fiscal policy related
      to health spending will not have an impact on economic growth; (2) For Belgium,
      Norway, and Mexico, only a unidirectional linear causality runs from health care
      expenditure to economic growth, while bidirectional linear causality can be found
      for Canada, Finland, Iceland, New Zealand, Spain, Brazil, and South Africa.
      Especially for the US, China, and Japan, a unidirectional nonlinear causality
      exists from health spending to economic growth. To improve the quality of
      national health, life quality and happiness, these 13 countries should actively
      look to optimise policy related to health care expenditure, such as by enhancing
      the efficiency of health costs to promote sustainable economic development.

PMID- 30205464
TI  - Enhancement in Curie Temperature of Yttrium Iron Garnet by Doping with Neodymium.
AB  - The effect of the substitution of Y3+ by Nd3+ on the structural and magnetic
      properties of neodymium-doped yttrium iron garnet, NdxY3-xFe5O12 with x in the
      range of 0-2.5, is presented. Oxide powders of Fe2O3, Nd2O3, and Y2O3 were mixed
      in a stoichiometric ratio and milled for 5 h using high-energy ball milling,
      before being uniaxially pressed at 900 MPa and annealed at 1373 K for 2 h to
      obtain NdxY3-xFe5O12 (0 <= x <= 2.5). It was found that the mechanical milling of
      oxides followed by annealing promotes the complete structural formation of the
      garnet structure. Additionally, the X-ray diffraction patterns confirm the
      complete introduction of Nd3+ into the garnet structure with a neodymium doping
      concentration (x) of 0-2.0, which causes a consistent increment in the lattice
      parameters with the Nd3+ content. When x is higher than 2.0, the yttrium
      orthoferrite is the predominant phase. Besides, the magnetic results reveal an
      increase in the Curie temperature (583 K) as the amount of Nd3+ increases, while
      there was enhanced saturation magnetization as well as modified remanence and
      coercivity with respect to non-doped YIG.

PMID- 30205465
TI  - Mothers and Children Exposed to Intimate Partner Violence: A Review of Treatment
      Interventions.
AB  - Although a growing field, much is still unknown about how different clinical and
      social care services might improve outcomes for female victims of intimate
      partner violence (IPV) and their children who are indirectly exposed to it. This
      review sought to characterize the structure of programs that have been tested and
      documented in existing literature, and the mechanisms by which change, if any,
      may occur. Seventeen individual interventions and two follow-ups (n = 19) were
      included in the review. Findings suggest that a multileveled program of mothers
      and children working both separately and jointly together across sessions might
      generate the most successful psychosocial recovery for mothers and children who
      have experienced violence in the home. The mechanism by which this happens is
      likely a collaborative one, focused on enhancing the dyadic interaction. This
      article adds to the growing evidence base on IPV and confirms the positive impact
      on well-being that programs for IPV victims can have. The evidence-base overall
      could benefit from testing and replicating a combination of the results found in
      this review.

PMID- 30205462
TI  - Insights into the Human Virome Using CRISPR Spacers from Microbiomes.
AB  - Due to recent advances in next-generation sequencing over the past decade, our
      understanding of the human microbiome and its relationship to health and disease
      has increased dramatically. Yet, our insights into the human virome, and its
      interplay with important microbes that impact human health, is relatively
      limited. Prokaryotic and eukaryotic viruses are present throughout the human
      body, comprising a large and diverse population which influences several niches
      and impacts our health at various body sites. The presence of prokaryotic viruses
      like phages, has been documented at many different body sites, with the human gut
      being the richest ecological niche. Clustered Regularly Interspaced Short
      Palindromic Repeats (CRISPR) and associated proteins constitute the adaptive
      immune system of bacteria, which prevents attack by invasive nucleic acid. CRISPR
      Cas systems function by uptake and integration of foreign genetic element
      sequences into the CRISPR array, which constitutes a genomic archive of iterative
      vaccination events. Consequently, CRISPR spacers can be investigated to
      reconstruct interplay between viruses and bacteria, and metagenomic sequencing
      data can be exploited to provide insights into host-phage interactions within a
      niche. Here, we show how the CRISPR spacer content of commensal and pathogenic
      bacteria can be used to determine the evidence of their phage exposure. This
      framework opens new opportunities for investigating host-virus dynamics in
      metagenomic data, and highlights the need to dedicate more efforts for virome
      sampling and sequencing.

PMID- 30205466
TI  - Strain-Induced Quantum Spin Hall Effect in Two-Dimensional Methyl-Functionalized
      Silicene SiCH3.
AB  - Quantum Spin Hall (QSH) has potential applications in low energy consuming
      spintronic devices and has become a researching hotspot recently. It benefits
      from insulators feature edge states, topologically protected from backscattering
      by time-reversal symmetry. The properties of methyl functionalized silicene
      (SiCH3) have been investigated using first-principles calculations, which show
      QSH effect under reasonable strain. The origin of the topological characteristic
      of SiCH3, is mainly associated with the s-pxy orbitals band inversion at Gamma
      point, whilst the band gap appears under the effect of spin-orbital coupling
      (SOC). The QSH phase of SiCH3 is confirmed by the topological invariant Z2 = 1,
      as well as helical edge states. The SiCH3 supported by hexagonal boron nitride
      (BN) film makes it possible to observe its non-trivial topological phase
      experimentally, due to the weak interlayer interaction. The results of this work
      provide a new potential candidate for two-dimensional honeycomb lattice
      spintronic devices in spintronics.

PMID- 30205467
TI  - Research on the Impact Loading and Energy Dissipation of Concrete after Elevated
      Temperature under Different Heating Gradients and Cooling Methods.
AB  - To provide theoretical basis for fire rescue, post-disaster safety evaluation,
      and reinforcement of concrete structures, C35 concrete materials are treated with
      high-temperature heating (200  degrees C, 400  degrees C, 600  degrees C, 800 
      degrees C) under two different heating gradients. After natural cooling and water
      cooling to normal temperature, an impact compression test was carried out at
      different loading rates using a Split Hopkinson Pressure Bar (SHPB) system with a
      diameter of 100 mm, and finally the crushed specimens were subjected to a sieving
      test. The effects of elevated temperatures, cooling methods, heating gradients,
      and loading rates on the fragment size distribution, fractal characteristics, and
      energy dissipation of impact-compressed concrete specimens were studied. The
      results show that with the increase of the loading rate and the rise of the
      heating temperature, the crushing degree of concrete specimens gradually
      increases, the average fragment size decreases, and the mass distribution of the
      fragments move from the coarse end to the fine end. The fragment size
      distribution of the specimen has obvious fractal characteristics. In addition,
      its fractal dimension increases with the increase of loading rate and heating
      temperature, the average size of the specimen fragments decreases
      correspondingly, and the fracture of the specimen becomes more serious. When the
      different heating gradients were compared, it was found that the fractal
      dimension of the specimens subjected to rapid heating treatment was larger than
      that of the slow heating treatment specimens, and the crushing degree of the
      specimens with different cooling methods was discrete. By analyzing the energy
      dissipation of the specimen under different conditions, it is shown that both the
      fractal dimension and the peak stress increase with the increase of the
      fragmentation energy dissipation density. It shows that there is a close
      correlation between the change of fractal dimension and its macroscopic dynamic
      mechanical properties.

PMID- 30205469
TI  - Design of Novel Pyrene-Bodipy Dyads: Synthesis, Characterization, Optical
      Properties, and FRET Studies.
AB  - A new series of dendronized bodipys containing pyrene units was synthesized and
      characterized. Their optical and photophysical properties were determined by
      absorption and fluorescence spectroscopy. This series includes three different
      compounds. The first one has an anisole group linked to the bodipy unit, which
      was used as the reference compound. In the second, the bodipy core is linked to a
      zero generation dendron with one pyrene unit. The third compound contains a first
      generation Frechet-type dendron bearing two pyrene units. In this work, the
      combination pyrene-bodipy was selected as the donor-acceptor pair for this
      fluorescence resonance energy transfer (FRET) study. Doubtless, these two
      chromophores exhibit high quantum yields, high extinction coefficients, and both
      their excitation and emission wavelengths are located in the visible region. This
      report presents a FRET study of a novel series of pyrene-bodipy dendritic
      molecules bearing flexible spacers. We demonstrated via spectroscopic studies
      that FRET phenomena occur in these dyads.

PMID- 30205468
TI  - Antimicrobial Photodynamic Inactivation Mediated by Rose Bengal and Erythrosine
      Is Effective in the Control of Food-Related Bacteria in Planktonic and Biofilm
      States.
AB  - The thermal and chemical-based methods applied for microbial control in the food
      industry are not always environmentally friendly and may change the nutritional
      and organoleptic characteristics of the final products. Moreover, the efficacy of
      sanitizing agents may be reduced when microbial cells are enclosed in biofilms.
      The objective of this study was to investigate the effect of photodynamic
      inactivation, using two xanthene dyes (rose bengal and erythrosine) as
      photosensitizing agents and green LED as a light source, against Staphylococcus
      aureus, Listeria innocua, Enterococcus hirae and Escherichia coli in both
      planktonic and biofilm states. Both photosensitizing agents were able to control
      planktonic cells of all bacteria tested. The treatments altered the
      physicochemical properties of cells surface and also induced potassium leakage,
      indicating damage of cell membranes. Although higher concentrations of the
      photosensitizing agents (ranging from 0.01 to 50.0 MUmol/L) were needed to be
      applied, the culturability of biofilm cells was reduced to undetectable levels.
      This finding was confirmed by the live/dead staining, where propidium iodide
      labeled bacteria numbers reached up to 100%. The overall results demonstrated
      that photoinactivation by rose bengal and erythrosine may be a powerful candidate
      for the control of planktonic cells and biofilms in the food sector.

PMID- 30205472
TI  - A Novel Nested Configuration Based on the Difference and Sum Co-Array Concept.
AB  - Recently, the concept of the difference and sum co-array (DSCa) has attracted
      much attention in array signal processing due to its high degree of freedom
      (DOF). In this paper, the DSCa of the nested array (NA) is analyzed and then an
      improved nested configuration known as the diff-sum nested array (DsNA) is
      proposed. We find and prove that the sum set for the NA contains all the elements
      in the difference set. Thus, there exists the dual characteristic between the two
      sets, i.e., for the difference result between any two sensor locations of the NA,
      one equivalent non-negative/non-positive sum result of two other sensor locations
      can always be found. In order to reduce the redundancy for further DOF
      enhancement, we develop a new DsNA configuration by moving nearly half the dense
      sensors of the NA to the right side of the sparse uniform linear array (ULA)
      part. These moved sensors together with the original sparse ULA form an extended
      sparse ULA. For analysis, we provide the closed form expressions of the DsNA
      locations as well as the DOF. Compared with some novel sparse arrays with large
      aperture such as the NA, coprime array and augmented nested array, the DsNA can
      achieve a higher number of DOF. The effectiveness of the proposed array is proved
      by the simulations.

PMID- 30205470
TI  - Estimating the Size of Dog Populations in Tanzania to Inform Rabies Control.
AB  - Estimates of dog population sizes are a prerequisite for delivering effective
      canine rabies control. However, dog population sizes are generally unknown in
      most rabies-endemic areas. Several approaches have been used to estimate dog
      populations but without rigorous evaluation. We compare post-vaccination
      transects, household surveys, and school-based surveys to determine which most
      precisely estimates dog population sizes. These methods were implemented across
      28 districts in southeast Tanzania, in conjunction with mass dog vaccinations,
      covering a range of settings, livelihoods, and religious backgrounds. Transects
      were the most precise method, revealing highly variable patterns of dog
      ownership, with human/dog ratios ranging from 12.4:1 to 181.3:1 across districts.
      Both household and school-based surveys generated imprecise and, sometimes,
      inaccurate estimates, due to small sample sizes in relation to the heterogeneity
      in patterns of dog ownership. Transect data were subsequently used to develop a
      predictive model for estimating dog populations in districts lacking transect
      data. We predicted a dog population of 2,316,000 (95% CI 1,573,000-3,122,000) in
      Tanzania and an average human/dog ratio of 20.7:1. Our modelling approach has the
      potential to be applied to predicting dog population sizes in other areas where
      mass dog vaccinations are planned, given census and livelihood data. Furthermore,
      we recommend post-vaccination transects as a rapid and effective method to refine
      dog population estimates across large geographic areas and to guide dog
      vaccination programmes in settings with mostly free roaming dog populations.

PMID- 30205471
TI  - Relationship between Photosynthetic Capacity and Microcystin Production in Toxic
      Microcystis Aeruginosa under Different Iron Regimes.
AB  - Blooms of harmful cyanobacteria have been observed in various water bodies across
      the world and some of them can produce intracellular toxins, such as microcystins
      (MCs), which negatively impact aquatic organisms and human health. Iron
      participates significantly in cyanobacterial photosynthesis and is proposed to be
      linked to MC production. Here, the cyanobacteria Microcystis aeruginosa was
      cultivated under different iron regimes to investigate the relationship between
      photosynthetic capacity and MC production. The results showed that iron addition
      increased cell density, cellular protein concentration and the Chl-a (chlorophyll
      a) content. Similarly, it can also up-regulate photosynthetic capacity and
      promote MC-leucine-arginine (MC-LR) production, but not in a dose-dependent
      manner. Moreover, a significant positive correlation between photosynthetic
      capacity and MC production was observed, and electron transport parameters were
      the most important parameters contributing to the variation of intracellular MC
      LR concentration revealed by Generalized Additive Model analysis. As the electron
      transport chain was affected by iron variation, adenosine triphosphate production
      was inhibited, leading to the alteration of MC synthetase gene expression.
      Therefore, it is demonstrated that MC production greatly relies on redox status
      and energy metabolism of photosynthesis in M. aeruginosa. In consequence, more
      attention should be paid to the involvement of photosynthesis in the regulation
      of MC production by iron variation in the future.

PMID- 30205473
TI  - A Computational Method for Classifying Different Human Tissues with
      Quantitatively Tissue-Specific Expressed Genes.
AB  - Tissue-specific gene expression has long been recognized as a crucial key for
      understanding tissue development and function. Efforts have been made in the past
      decade to identify tissue-specific expression profiles, such as the Human
      Proteome Atlas and FANTOM5. However, these studies mainly focused on
      "qualitatively tissue-specific expressed genes" which are highly enriched in one
      or a group of tissues but paid less attention to "quantitatively tissue-specific
      expressed genes", which are expressed in all or most tissues but with
      differential expression levels. In this study, we applied machine learning
      algorithms to build a computational method for identifying "quantitatively tissue
      specific expressed genes" capable of distinguishing 25 human tissues from their
      expression patterns. Our results uncovered the expression of 432 genes as optimal
      features for tissue classification, which were obtained with a Matthews
      Correlation Coefficient (MCC) of more than 0.99 yielded by a support vector
      machine (SVM). This constructed model was superior to the SVM model using tissue
      enriched genes and yielded MCC of 0.985 on an independent test dataset,
      indicating its good generalization ability. These 432 genes were proven to be
      widely expressed in multiple tissues and a literature review of the top 23 genes
      found that most of them support their discriminating powers. As a complement to
      previous studies, our discovery of these quantitatively tissue-specific genes
      provides insights into the detailed understanding of tissue development and
      function.

PMID- 30205474
TI  - Colour Stabilization of Oak, Spruce, Larch and Douglas Fir Heartwood Treated with
      Mixtures of Nanoparticle Dispersions and UV-Stabilizers after Exposure to UV and
      VIS-Radiation.
AB  - Colour changes and associated wood degradation in exterior and interior
      applications influenced by ultraviolet (UV) and visible radiation (VIS) decreases
      the aesthetic value of the products and shortens the overall life of transparent
      coatings. The aim of the paper is to achieve colour stabilization of oak, larch,
      Douglas fir and spruce heartwood via surface treatment with UV stabilizers,
      hindered amine light stabilizers (HALS), nanoparticles TiO2, ZnO, and mixtures
      thereof, during exposure to UV and VIS radiation. Colour changes were evaluated
      during accelerated artificial ageing testing in Xenotest. The distinctly
      individual character of colour changes in surface treatments due to the
      underlying wood species was confirmed. A synergistic effect was found when using
      a combination of active substances compared to substances used individually. The
      mixture of benzotriazoles with HALS (Tinuvin 5151) in combination with TiO2 and
      ZnO nanoparticles was confirmed as one of the most effective treatments for
      colour stabilization of wood due to UV and VIS spectrums.

PMID- 30205475
TI  - Challenges of Decoding Transcription Factor Dynamics in Terms of Gene Regulation.
AB  - Technological advances are continually improving our ability to obtain more
      accurate views about the inner workings of biological systems. One such rapidly
      evolving area is single cell biology, and in particular gene expression and its
      regulation by transcription factors in response to intrinsic and extrinsic
      factors. Regarding the study of transcription factors, we discuss some of the
      promises and pitfalls associated with investigating how individual cells regulate
      gene expression through modulation of transcription factor activities.
      Specifically, we discuss four leading experimental approaches, the data that can
      be obtained from each, and important considerations that investigators should be
      aware of when drawing conclusions from such data.

PMID- 30205476
TI  - Classification of Overt and Covert Speech for Near-Infrared Spectroscopy-Based
      Brain Computer Interface.
AB  - People suffering from neuromuscular disorders such as locked-in syndrome (LIS)
      are left in a paralyzed state with preserved awareness and cognition. In this
      study, it was hypothesized that changes in local hemodynamic activity, due to the
      activation of Broca's area during overt/covert speech, can be harnessed to create
      an intuitive Brain Computer Interface based on Near-Infrared Spectroscopy (NIRS).
      A 12-channel square template was used to cover inferior frontal gyrus and changes
      in hemoglobin concentration corresponding to six aloud (overtly) and six silently
      (covertly) spoken words were collected from eight healthy participants. An
      unsupervised feature extraction algorithm was implemented with an optimized
      support vector machine for classification. For all participants, when considering
      overt and covert classes regardless of words, classification accuracy of 92.88 +/
      18.49% was achieved with oxy-hemoglobin (O2Hb) and 95.14 +/- 5.39% with deoxy
      hemoglobin (HHb) as a chromophore. For a six-active-class problem of overtly
      spoken words, 88.19 +/- 7.12% accuracy was achieved for O2Hb and 78.82 +/- 15.76%
      for HHb. Similarly, for a six-active-class classification of covertly spoken
      words, 79.17 +/- 14.30% accuracy was achieved with O2Hb and 86.81 +/- 9.90% with
      HHb as an absorber. These results indicate that a control paradigm based on
      covert speech can be reliably implemented into future Brain-Computer Interfaces
      (BCIs) based on NIRS.

PMID- 30205477
TI  - Genome-Wide Analysis Elucidates the Role of CONSTANS-like Genes in Stress
      Responses of Cotton.
AB  - The CONSTANS (CO)-like gene family has been well studied for its role in the
      regulation of plant flowering time. However, their role remains poorly understood
      in cotton. To better understand the possible roles of CO-like in cotton, we
      performed a comprehensive genome-wide analysis of CO-like genes in cotton.
      Phylogenetic tree analysis showed that CO-like genes naturally clustered into
      three groups. Segmental duplication and whole genome duplication (WGD), which
      occurred before polyploidy, were important contributors to its expansion within
      the At ("t" indicates tetraploid) and Dt subgenomes, particularly in Group III.
      Long-terminal repeat retroelements were identified as the main transposable
      elements accompanying 18 genes. The genotype of GhCOL12_Dt displayed low
      diversity; it was a candidate involved in domestication. Selection pressure
      analyses indicated that relaxed purifying selection might have provided the main
      impetus during the evolution of CO-like genes in upland cotton. In addition, the
      high expression in the torus and calycle indicated that CO-like genes might
      affect flowering. The genes from Group II, and those from Group III involved in
      segmental duplication or WGD, might play important roles in response to drought
      and salt stress. Overall, this comprehensive genome-wide study of the CO-like
      gene family would facilitate further detailed studies in cotton.

PMID- 30205479
TI  - Attitudes toward Nutrition and Dietary Habits and Effectiveness of Nutrition
      Education in Active Adolescents in a Private School Setting: A Pilot Study.
AB  - This study was designed to pilot a survey to investigate nutrition knowledge,
      attitudes, and beliefs toward nutrition, exercise, and dietary habits of active
      adolescents. Participants included 117 middle school and 40 high school students.
      General and sport nutrition knowledge, dietary habits, and attitudes toward
      nutrition education were collected via three electronic surveys. Among middle
      schoolers, 79.5% of students stated feeling they could benefit from advice about
      nutrition compared to 92.5% of high school students. The topic scoring the
      highest in both populations was hydration; the lowest scoring topic category was
      protein and exercise. Knowledge about healthy eating reportedly comes from
      parents and coaches most frequently for both high school and middle school
      students. Less than 40% of students stated their diet meets their nutritional
      needs. Both middle school and high school students stated a desire to learn more
      about nutrition, but most nutrition information currently received comes from non
      nutrition-related professionals. There is a need for validation of a nutrition
      knowledge and behavior instrument for United States adolescents, and room for
      improvement in general and sport nutrition knowledge in active adolescents in all
      topic areas.

PMID- 30205478
TI  - Metalenses Based on Symmetric Slab Waveguide and c-TiO2: Efficient Polarization
      Insensitive Focusing at Visible Wavelengths.
AB  - A key goal of metalens research is to achieve wavefront shaping of light using
      optical elements with thicknesses on the order of the wavelength. Here we
      demonstrate ultrathin highly efficient crystalline titanium dioxide metalenses at
      blue, green, and red wavelengths (lambda0 = 453 nm, 532 nm, and 633 nm,
      respectively) based on symmetric slab waveguide theory. These metalenses are less
      than 488 nm-thick and capable of focusing incident light into very symmetric
      diffraction-limited spots with strehl ratio and efficiency as high as 0.96 and
      83%, respectively. Further quantitative characterizations about metalenses' peak
      focusing intensities and focal spot sizes show good agreement with theoretical
      calculation. Besides, the metalenses suffer only about 10% chromatic deviation
      from the ideal spots in visible spectrum. In contrast with Pancharatnam-Berry
      phase mechanism, which limit their incident light at circular polarization, the
      proposed method enables metalenses polarization-insensitive to incident light.

PMID- 30205480
TI  - Indoor Localization Based on Weighted Surfacing from Crowdsourced Samples.
AB  - Fingerprinting-based indoor localization suffers from its time-consuming and
      labor-intensive site survey. As a promising solution, sample crowdsourcing has
      been recently promoted to exploit casually collected samples for building offline
      fingerprint database. However, crowdsourced samples may be annotated with
      erroneous locations, which raises a serious question about whether they are
      reliable for database construction. In this paper, we propose a cross-domain
      cluster intersection algorithm to weight each sample reliability. We then select
      those samples with higher weight to construct radio propagation surfaces by
      fitting polynomial functions. Furthermore, we employ an entropy-like measure to
      weight constructed surfaces for quantifying their different subarea consistencies
      and location discriminations in online positioning. Field measurements and
      experiments show that the proposed scheme can achieve high localization accuracy
      by well dealing with the sample annotation error and nonuniform density
      challenges.

PMID- 30205481
TI  - Thermoresponsive Core-Shell Nanoparticles: Does Core Size Matter?
AB  - Nanoparticles grafted with a dense brush of hydrophilic polymers exhibit high
      colloidal stability. However, reversible aggregation can be triggered by an
      increase in temperature if the polymer is thermoresponsive, as the polymer shell
      partly loses its hydration. We investigate the role of nanoparticle curvature on
      the critical solution temperature (CST) of grafted poly(2-isopropyl-2-oxazoline)
      (PiPOx) and critical flocculation temperature (CFT) of the core-shell
      nanoparticle dispersion. Cores with diameters ranging from 5 to 21 nm were
      studied by temperature-cycled dynamic light scattering and differential scanning
      calorimetry over a large range of concentrations. We show that core size and
      curvature only have a minor influence on particle aggregation (CFT and cluster
      size), while they have major influence on the CST of the polymer shell. The
      densely grafted shells exhibit three distinct solvation transitions, the relative
      contributions of each is controlled by the core curvature. We link these
      transitions to different polymer density regimes within the spherical brush and
      demonstrate that the CST of the innermost part of the brush coincides with the
      CFT of the particle dispersion.

PMID- 30205482
TI  - Comparative Transcriptomics Identifies Novel Genes and Pathways Involved in Post
      Traumatic Osteoarthritis Development and Progression.
AB  - Anterior cruciate ligament (ACL) injuries often result in post-traumatic
      osteoarthritis (PTOA). To better understand the molecular mechanisms behind PTOA
      development following ACL injury, we profiled ACL injury-induced transcriptional
      changes in knee joints of three mouse strains with varying susceptibility to OA:
      STR/ort (highly susceptible), C57BL/6J (moderately susceptible) and super-healer
      MRL/MpJ (not susceptible). Right knee joints of the mice were injured using a non
      invasive tibial compression injury model and global gene expression was
      quantified before and at 1-day, 1-week, and 2-weeks post-injury using RNA-seq.
      Following injury, injured and uninjured joints of STR/ort and injured C57BL/6J
      joints displayed significant cartilage degeneration while MRL/MpJ had little
      cartilage damage. Gene expression analysis suggested that prolonged inflammation
      and elevated catabolic activity in STR/ort injured joints, compared to the other
      two strains may be responsible for the severe PTOA phenotype observed in this
      strain. MRL/MpJ had the lowest expression values for several inflammatory
      cytokines and catabolic enzymes activated in response to ACL injury. Furthermore,
      we identified several genes highly expressed in MRL/MpJ compared to the other two
      strains including B4galnt2 and Tpsab1 which may contribute to enhanced healing in
      the MRL/MpJ. Overall, this study has increased our knowledge of early molecular
      changes associated with PTOA development.

PMID- 30205483
TI  - Impact of Exergaming on Children's Motor Skill Competence and Health-Related
      Fitness: A Quasi-Experimental Study.
AB  - This study was designed to examine the effectiveness of a combined exergaming and
      physical education (PE) program on children's motor skill competence (MSC) and
      health-related fitness (HRF) as compared to traditional PE. A total of 261 second
      and third-grade children (127 boys; 8.25 +/- 0.66 years for male; 8.29 +/- 0.74
      years for female; 73.6% non-Hispanic white) participated in the nine-month study
      from 2012 to 2013. Children were assigned to one of the two groups: (a)
      intervention group (125 min of alternating PE and exergaming weekly); and (b)
      comparison group (125-min weekly PE). MSC was assessed via product scores in two
      locomotor and two object control skills. HRF included the cardiorespiratory
      fitness, musculoskeletal fitness, and body mass index (BMI). A multivariate
      analysis of variance (MANOVA) was performed to analyze the effect of the combined
      exergaming-PE program on children's MSC and HRF. There were significant group by
      time interaction effects for BMI, p < 0.01, eta2 = 0.20; musculoskeletal fitness,
      p < 0.01, eta2 = 0.13; and object control skills (the comparison group
      demonstrating greater improvement), p = 0.01, eta2 = 0.03. The findings suggest
      that the combined exergaming program can have a positive effect on children's BMI
      and musculoskeletal fitness, indicating that exergaming can be an alternative
      school-based program to supplement traditional PE.

PMID- 30205484
TI  - Low-Calorie Beverage Consumption, Diet Quality and Cardiometabolic Risk Factors
      in British Adults.
AB  - Low-calorie beverages (LCBs) are promoted as healthy alternatives to sugar
      sweetened beverages (SSBs); however, their effects on diet quality and
      cardiometabolic profile are debatable. This study aimed to verify the association
      between LCB consumption, diet quality and cardiometabolic risk factors in British
      adults. Data analysis from 5521 subjects aged 16 and older who participated in
      two waves of the National Diet and Nutrition Survey Rolling Programme (2008-2012
      and 2013-2014) was carried out. Compared with SSB consumption, LCB consumption
      was associated with lower energy (mean difference: -173 kcal, 95% confidence
      interval, CI: -212; -133) and free sugar intake (-5.6% of energy intake, 95% CI: 
      6.1; -5.1), while intake of other nutrients was not significantly different
      across groups. The % difference in sugar intake was more pronounced among the
      young (16-24 years) (-7.3 of energy intake, 95% CI: -8.6; -5.9). The odds of not
      exceeding the UK-recommended free sugar intake were remarkably higher in the LCB
      as compared to the SSB group (OR: 9.4, 95% CI: 6.5-13.6). No significant
      differences were observed in plasma glucose, total cholesterol, LDL, HDL or
      triglycerides. Our findings suggest that LCBs are associated with lower free
      sugar intake without affecting the intake of other macronutrients or negatively
      impacting cardiometabolic risk factors.

PMID- 30205486
TI  - Potential Gastroprotective Activity of Rice Bran (Oryza sativa L.) Extracted by
      Ionic Liquid-Microwave-Assisted Extraction against Ethanol-Induced Acute Gastric
      Ulcers in Rat Model.
AB  - The presence of gamma-oryzanol in rice bran oil can be 10-20-fold higher than
      tocopherol and tocotrienol. Gamma-oryzanol has various pharmacological
      properties. The objective of this study was to evaluate the effectiveness of rice
      bran extract as a gastroprotective in reducing lesions in ethanol-induced acute
      gastric ulcer models in rat, using the ionic liquid-microwave-assisted extraction
      (IL-MAE) method. Rice bran extract was obtained using the IL-MAE method with
      ionic liquid (IL), 1-butyl-3-methylimidazolium tetrafluoroborate [BMIM]BF4
      (concentration 0.7 M), and a ratio of solid/liquid of 15 g/mL, 15 min extraction
      time, and 10% microwave power. The rats were pretreated with rice bran extract at
      different doses (100, 200, and 400 mg/kg body weight; BW) for seven days and
      subsequently exposed to acute gastric lesions induced by 80% ethanol. Omeprazole
      (36 mg/kg BW) was used as a standard anti-ulcer drug. The ulcer index, gastric
      juice acidity, and mucus levels were measured to assess the degree of
      gastroprotection. The results showed that the oral administration of rice bran
      extract at a dose of 400 mg/kg BW significantly inhibited the development of
      ulcer formation by 66.75% and reduced gastric acid levels. Moreover, gamma
      oryzanol and omeprazole protected the gastric mucosa from ethanol-induced gastric
      lesions by increasing the level of gastric mucus. Rice bran extract is effective
      as a gastroprotective therapy sourced from natural ingredients in treating the
      incidence of gastric ulcers. Most likely, this is related to gamma oryzanol as a
      bioactive compound contained in rice bran (Oryza sativa L.).

PMID- 30205485
TI  - Rational Design for Multicolor Flavone-Based Fluorophores with Aggregation
      Induced Emission Enhancement Characteristics and Applications in Mitochondria
      Imaging.
AB  - Fluorophores with aggregation-induced emission enhancement (AIEE) properties have
      attracted more attention in recent years. In order to realise more valuable
      applications, the different kinds of AIEE molecules are in serious need of
      further development. Therefore, a novel flavone-based AIEE system derived from
      restriction of intramolecular rotation (RIR) was designed and synthesized in this
      work. The results revealed that six of the compounds showed typical AIEE
      characteristics, with fluorescence emissions from purple, blue, cyan to green,
      tunable by changing substituent groups. This flavone-based AIEE system has never
      been reported before. The AIEE characteristics were investigated by optical
      spectroscopy, fluorescence photographs, scanning electron microscopy (SEM),
      fluorescence quantum yields (FF) and fluorescence lifetime in the CH3OH/H2O mixed
      solution. Moreover, benefiting from the simple structures and small molecular
      weight, they could permeate cells faster than current high-molecular-weight AIEE
      molecules. Furthermore, to examine possible biomedical applications, fluorescence
      imaging in living A549 lung cells and cell viabilities were examined, and the
      results displayed that these fluorophores showed good cellular uptake and low
      cytotoxicity within the experimental concentration range. In addition, these AIEE
      compounds possessed excellent specificity for mitochondrial targeting and
      mitochondrial morphological change tracking, besides, they displayed superior
      photostability, which indicated they are potential candidates for mitochondrial
      imaging.

PMID- 30205487
TI  - Preparation of Highly Catalytic N-Doped Carbon Dots and Their Application in SERS
      Sulfate Sensing.
AB  - Carbon dots (CD) have excellent stability and fluorescence activity, and have
      been widely used in fluorescence methods. However, there are no reports about
      using CD as catalysts to amplify SERS signals to detect trace sulfate. Thus,
      preparing CD catalysts and their application in SERS sulfate-sensing are
      significant. In this article, highly catalytic N-doped carbon dots (CDN) were
      prepared by a hydrothermal procedure. CDN exhibited strong catalysis of the gold
      nanoparticle (AuNP) reaction between HAuCl4 and H2O2. Vitoria blue 4R (VB4R) has
      a strong SERS peak at 1614 cm-1 in the formed AuNP sol substrate. When Ba2+ ions
      were added, they were adsorbed on a CDN surface to inhibit the CDN catalytic
      activity that caused the SERS peak decreasing. Upon addition of analyte SO42-, a
      reaction with Ba2+ produced stable BaSO4 precipitate and CDN, and its catalysis
      recovered to cause SERS intensity increasing linearly. Thus, an SERS method was
      developed for the detection of 0.02-1.7 MUmol/L SO42-, with a detection limit of
      0.007 MUmol/L.

PMID- 30205489
TI  - One-Step Chemical Vapor Deposition Synthesis of 3D N-doped Carbon Nanotube/N
      doped Graphene Hybrid Material on Nickel Foam.
AB  - 3D hybrid nanostructures connecting 1D carbon nanotubes (CNTs) with 2D graphene
      have attracted more and more attentions due to their excellent chemical, physical
      and electrical properties. In this study, we firstly report a novel and facile
      one-step process using template-directed chemical vapor deposition (CVD) to
      fabricate highly nitrogen doped three-dimensional (3D) N-doped carbon nanotubes/N
      doped graphene architecture (N-CNTs/N-graphene). We used nickel foam as
      substrate, melamine as a single source for both carbon and nitrogen,
      respectively. The morphology and microstructure were characterized by scanning
      electron microscopy, transmission electron microscopy, X-ray diffraction,
      isothermal analyses, X-ray photoelectron microscopy and Raman spectra. The
      obtained 3D N-CNTs/N-graphene exhibits high graphitization, a regular 3D
      structure and excellent nitrogen doping and good mesoporosity.

PMID- 30205488
TI  - TREM-1; Is It a Pivotal Target for Cardiovascular Diseases?
AB  - Cardiovascular diseases (CVDs) are as menacing as ever and still continue to kill
      adults worldwide, notwithstanding tremendous efforts to decrease their consequent
      mortality and morbidity. Lately, a growing body of research indicated that
      inflammation plays a pivotal role in the pathogenesis and complications of CVDs.
      A receptor of the immunoglobulin superfamily, triggering receptors expressed on
      myeloid cells-1 (TREM-1) was shown to induce and amplify the inflammation in both
      acute and chronic disease' pathogenesis and progression, which hence makes it one
      of the most important complication factors of CVDs. Thus, studies endeavored to
      investigate the role played by TREM-1 in CVDs with respect to their etiologies,
      complications, and possible therapeutics. We examined here, for the first time,
      the most relevant studies regarding TREM-1 involvement in CVDs. We critically
      analyzed and summarized our findings and made some suggestions for furtherance of
      the investigations with the aim to utilize TREM-1 and its pathways for
      diagnostic, management, and prognosis of CVDs. Overall, TREM-1 was found to be
      involved in the pathogenesis of acute and chronic cardiovascular conditions, such
      as acute myocardial infarction (AMI) and atherosclerosis. Although most
      therapeutic approaches are yet to be elucidated, our present research outcome
      displays a promising future to utilizing the TREM-1 pathway as a potential target
      for understanding and managing CVDs.

PMID- 30205490
TI  - NLOS Identification and Positioning Algorithm Based on Localization Residual in
      Wireless Sensor Networks.
AB  - The problem of target localization in WSN (wireless sensor network) has received
      much attention in recent years. However, the performance of traditional
      localization algorithms will drastically degrade in the non-line of sight (NLOS)
      environment. Moreover, variable methods have been presented to address this
      issue, such as the optimization-based method and the NLOS modeling method. The
      former produces a higher complexity and the latter is sensitive to the
      propagating environment. Therefore, this paper puts forward a simple NLOS
      identification and localization algorithm based on the residual analysis, where
      at least two line-of-sight (LOS) propagating anchor nodes (AN) are required.
      First, all ANs are grouped into several subgroups, and each subgroup can get
      intermediate position estimates of target node through traditional localization
      algorithms. Then, the AN with an NLOS propagation, namely NLOS-AN, can be
      identified by the threshold based hypothesis test, where the test variable, i.e.,
      the localization residual, is computed according to the intermediate position
      estimations. Finally, the position of target node can be estimated by only using
      ANs under line of sight (LOS) propagations. Simulation results show that the
      proposed algorithm can successfully identify the NLOS-AN, by which the following
      localization produces high accuracy so long as there are no less than two LOS
      ANs.

PMID- 30205492
TI  - LDL-Cholesterol Lowering of Plant Sterols and Stanols-Which Factors Influence
      Their Efficacy?
AB  - The LDL-cholesterol (LDL-C) lowering effect of plant sterols/stanols (PSS) is
      summarized in several meta-analyses showing a dose-response relationship with
      intakes of 1.5 to 3 g/day lowering LDL-C by 7.5% to 12%. This review summarizes
      evidence for the impact of various factors potentially influencing the LDL-C
      lowering efficacy of PSS. PSS are efficacious in all food formats and in food
      supplements. Some factors related to food format, e.g., solid vs. liquid foods,
      seem to impact efficacy, while there is no difference between free PSS and
      esters. Compared to multiple daily intakes, once-a-day intake of PSS, especially
      in the morning with light breakfast, leads to a sub-optimal LDL-C lowering.
      However, intake frequency seems influenced by intake occasion, i.e., with or
      without a meal, and time of day. Meal intake is a critical factor for an optimal
      LDL-C lowering efficacy of PSS. While age has no impact, gender is suggested to
      influence the LDL-C lowering effect of PSS with greater reductions reported for
      men than women; but overall evidence is inconclusive and larger studies show no
      gender by treatment interaction. In conclusion, PSS are efficacious in all foods
      and food supplements; for optimal efficacy they should be consumed with a (main)
      meal and twice daily.

PMID- 30205491
TI  - Potential Metabolomic Linkage in Blood between Parkinson's Disease and Traumatic
      Brain Injury.
AB  - The etiologic basis for sporadic forms of neurodegenerative diseases has been
      elusive but likely represents the product of genetic predisposition and various
      environmental factors. Specific gene-environment interactions have become more
      salient owing, in part, to the elucidation of epigenetic mechanisms and their
      impact on health and disease. The linkage between traumatic brain injury (TBI)
      and Parkinson's disease (PD) is one such association that currently lacks a
      mechanistic basis. Herein, we present preliminary blood-based metabolomic
      evidence in support of potential association between TBI and PD. Using untargeted
      and targeted high-performance liquid chromatography-mass spectrometry we
      identified metabolomic biomarker profiles in a cohort of symptomatic mild TBI
      (mTBI) subjects (n = 75) 3-12 months following injury (subacute) and TBI controls
      (n = 20), and a PD cohort with known PD (n = 20) or PD dementia (PDD) (n = 20)
      and PD controls (n = 20). Surprisingly, blood glutamic acid levels in both the
      subacute mTBI (increased) and PD/PDD (decreased) groups were notably altered from
      control levels. The observed changes in blood glutamic acid levels in mTBI and
      PD/PDD are discussed in relation to other metabolite profiling studies. Should
      our preliminary results be replicated in comparable metabolomic investigations of
      TBI and PD cohorts, they may contribute to an "excitotoxic" linkage between TBI
      and PD/PDD.

PMID- 30205493
TI  - Sex Differences in Hepatic De Novo Lipogenesis with Acute Fructose Feeding.
AB  - Dietary free sugars have received much attention over the past few years. Much of
      the focus has been on the effect of fructose on hepatic de novo lipogenesis
      (DNL). Therefore the aim of the present study was to investigate the effects of
      meals high and low in fructose on postprandial hepatic DNL and fatty acid
      partitioning and dietary fatty acid oxidation. Sixteen healthy adults (eight men,
      eight women) participated in this randomised cross-over study; study days were
      separated by a 4-week wash-out period. Hepatic DNL and dietary fatty acid
      oxidation were assessed using stable-isotope tracer methodology. Consumption of
      the high fructose meal significantly increased postprandial hepatic DNL to a
      greater extent than consumption of the low fructose meal and this effect was
      evident in women but not men. Despite an increase in hepatic DNL, there was no
      change in dietary fatty acid oxidation. Taken together, our data show that women
      are more responsive to ingestion of higher amounts of fructose than men and if
      continued over time this may lead to changes in hepatic fatty acid partitioning
      and eventually liver fat content.

PMID- 30205494
TI  - Development of Potentiometric Sensors for C2H4 Detection.
AB  - Gas exhaust emissions in vehicles are increasingly restrictive in EU and USA.
      Diesel engines are particularly affected by limitation in hydrocarbons and NOx
      concentrations. This work presents a screening of working electrode materials to
      develop a potentiometric sensor, with the most promising material to detect being
      C2H4 at 550  degrees C. The device consists of a dense 8YSZ (8 mol% Y2O3
      stabilized ZrO2) disk as oxide-ion conducting electrolyte, whereas platinum is
      screen-printed in the back face as reference electrode. As working electrode,
      several materials such as Fe0.7Cr1.3O3, ZnCr2O4, Fe2NiO4, La0.8Sr0.2CrO3-delta
      (LSC), La0.8Sr0.2MnO3 (LSM), and NiO+5%wt Au were tested to detect C2H4. Sensor
      voltage was measured for several concentrations of C2H4 and CO as these are two
      of the major oxidizable compounds in a diesel exhaust gas. Fe0.7Cr1.3O3 was
      selected as the most promising material because of its response to C2H4 and CO.
      Not only is the response to the individual analytes important, but the C2H4 cross
      sensitivity toward CO is also important. Fe0.7Cr1.3O3 showed a good performance
      to C2H4, with low cross-sensitivity to CO. In addition, when 0.16 ppm of
      phenanthrene is added, the sensor still has a slightly better response to C2H4
      than to CO. Nevertheless, the sensor exposure to high concentrations (>85 ppm) of
      polycyclic aromatic hydrocarbons led to signal saturation. On the other hand, the
      operation in wet conditions induces lower sensor sensitivity to C2H4 and higher
      cross-sensitivity toward CO increase, i.e., the sensor response becomes similar
      for C2H4 and CO.

PMID- 30205495
TI  - Novel Group of AChE Reactivators-Synthesis, In Vitro Reactivation and Molecular
      Docking Study.
AB  - The acetylcholinesterase (AChE) reactivators (e.g., obidoxime, asoxime) became an
      essential part of organophosphorus (OP) poisoning treatment, together with
      atropine and diazepam. They are referred to as a causal treatment of OP
      poisoning, because they are able to split the OP moiety from AChE active site and
      thus renew its function. In this approach, fifteen novel AChE reactivators were
      determined. Their molecular design originated from former K-oxime compounds K048
      and K074 with remaining oxime part of the molecule and modified part with
      heteroarenium moiety. The novel compounds were prepared, evaluated in vitro on
      human AChE (HssAChE) inhibited by tabun, paraoxon, methylparaoxon or DFP and
      compared to commercial HssAChE reactivators (pralidoxime, methoxime, trimedoxime,
      obidoxime, asoxime) or previously prepared compounds (K048, K074, K075, K203).
      Some of presented oxime reactivators showed promising ability to reactivate
      HssAChE comparable or higher than the used standards. The molecular modelling
      study was performed with one compound that presented the ability to reactivate GA
      inhibited HssAChE. The SAR features concerning the heteroarenium part of the
      reactivator's molecule are described.

PMID- 30205496
TI  - Associations between Flavonoid Intakes and Gut Microbiota in a Group of Adults
      with Cystic Fibrosis.
AB  - Dietary flavonoid intakes can influence gut microbiota (GM), which in turn can
      affect immune function and host metabolism, both vital considerations in cystic
      fibrosis (CF) management. In CF, GM may be altered and link to CF respiratory
      events. This study explored the relationship between flavonoid intakes and GM in
      free-living adults with CF. Associations between the overall GM variations
      (unweighted and weighted UniFrac distances between pyrosequencing results of
      bacterial 16-ss rDNA from frozen faecal samples of sixteen CF adults) and
      standardised dietary flavonoid intakes (a validated flavonoid-specific food
      frequency questionnaire) were analysed using adonis tests. Flavonoid intakes that
      were significant at a false discovery rate (FDR) < 0.3 were subjected to Spearman
      correlation tests with standardised bacterial relative abundances (FDR < 0.3).
      Gallocatechin intakes (p = 0.047, q = 0.285) were associated with unweighted
      UniFrac distances. Intakes of apigenin (p = 0.028, q = 0.227) and kaempferol (p =
      0.029, q = 0.227), and % flavonoid intake as flavones (p = 0.013, q = 0.227) and
      flavonols (p = 0.016, q = 0.227) (both excluding contribution of tea) were
      associated with weighted UniFrac distances. Among these, gallocatechin correlated
      with the genus Actinomyces and family Actinomycetaceae (Actinobacteria).
      Gallocatechin correlated negatively with class Coriobacteriia (Actinobacteria).
      Intakes of some flavonoids may be associated with GM variations with potential
      consequences for metabolism, immune function, and inflammation, which are
      important in CF lung disease and co-morbidity management.

PMID- 30205498
TI  - A System for In-Line 3D Inspection without Hidden Surfaces.
AB  - This work presents a 3D scanner able to reconstruct a complete object without
      occlusions, including its surface appearance. The technique presents a number of
      differences in relation to current scanners: it does not require mechanical
      handling like robot arms or spinning plates, it is free of occlusions since the
      scanned part is not resting on any surface and, unlike stereo-based methods, the
      object does not need to have visual singularities on its surface. This system,
      among other applications, allows its integration in production lines that require
      the inspection of a large volume of parts or products, especially if there is an
      important variability of the objects to be inspected, since there is no
      mechanical manipulation. The scanner consists of a variable number of industrial
      quality cameras conveniently distributed so that they can capture all the
      surfaces of the object without any blind spot. The object is dropped through the
      common visual field of all the cameras, so no surface or tool occludes the views
      that are captured simultaneously when the part is in the center of the visible
      volume. A carving procedure that uses the silhouettes segmented from each image
      gives rise to a volumetric representation and, by means of isosurface generation
      techniques, to a 3D model. These techniques have certain limitations on the
      reconstruction of object regions with particular geometric configurations.
      Estimating the inherent maximum error in each area is important to bound the
      precision of the reconstruction. A number of experiments are presented reporting
      the differences between ideal and reconstructed objects in the system.

PMID- 30205497
TI  - Iontophoretic Transdermal Delivery of Human Growth Hormone (hGH) and the
      Combination Effect of a New Type Microneedle, Tappy Tok Tok(r).
AB  - Transdermal drug administration presents several advantages and it is therefore
      favorable as an alternative drug delivery route. However, transdermal delivery of
      biopharmaceutical drugs is made difficult by the skin barrier. Microneedle
      application and iontophoresis are strategies which can be used to overcome this
      barrier. Therefore, recombinant human growth hormone (rhGH) was used as a model
      macromolecular drug and was transdermally delivered using microneedle application
      and iontophoresis. Methylene blue staining, stereomicroscopy and scanning
      electron microscope (SEM) imaging were used to characterize the microchannels
      produced. To optimize the iontophoresis protocol, the effects of molecular charge
      and current density on transdermal delivery were evaluated in an in vitro
      permeation study using excised rat skin tissues. Using the optimized
      iontophoresis protocol, the combination effects of iontophoretic delivery via
      microchannels were evaluated in three different experimental designs. The flux
      obtained with anodal iontophoresis in citrate buffer was approximately 10-fold
      higher that that with cathodal iontophoresis in phosphate buffered saline (PBS).
      Flux also increased with current density in anodal iontophoresis. The combination
      of iontophoresis and microneedle application produced higher flux than single
      application. These results suggest that anodal iontophoresis with higher current
      density enhances the permeation of macromolecules through microchannels created
      by microneedles. In conclusion, the combination of iontophoresis and microneedles
      is a potential strategy for the enhancement of transdermal delivery of
      macromolecular drugs.

PMID- 30205499
TI  - Urban Planning and Smart City Decision Management Empowered by Real-Time Data
      Processing Using Big Data Analytics.
AB  - The Internet of Things (IoT), inspired by the tremendous growth of connected
      heterogeneous devices, has pioneered the notion of smart city. Various
      components, i.e., smart transportation, smart community, smart healthcare, smart
      grid, etc. which are integrated within smart city architecture aims to enrich the
      quality of life (QoL) of urban citizens. However, real-time processing
      requirements and exponential data growth withhold smart city realization.
      Therefore, herein we propose a Big Data analytics (BDA)-embedded experimental
      architecture for smart cities. Two major aspects are served by the BDA-embedded
      smart city. Firstly, it facilitates exploitation of urban Big Data (UBD) in
      planning, designing, and maintaining smart cities. Secondly, it occupies BDA to
      manage and process voluminous UBD to enhance the quality of urban services. Three
      tiers of the proposed architecture are liable for data aggregation, real-time
      data management, and service provisioning. Moreover, offline and online data
      processing tasks are further expedited by integrating data normalizing and data
      filtering techniques to the proposed work. By analyzing authenticated datasets,
      we obtained the threshold values required for urban planning and city operation
      management. Performance metrics in terms of online and offline data processing
      for the proposed dual-node Hadoop cluster is obtained using aforementioned
      authentic datasets. Throughput and processing time analysis performed with regard
      to existing works guarantee the performance superiority of the proposed work.
      Hence, we can claim the applicability and reliability of implementing proposed
      BDA-embedded smart city architecture in the real world.

PMID- 30205501
TI  - Creating the Coupled Band Gaps in Piezoelectric Composite Plates by
      Interconnected Electric Impedance.
AB  - In this paper, we investigate the coupled band gaps created by the locking
      phenomenon between the electric and flexural waves in piezoelectric composite
      plates. To do that, the distributed piezoelectric materials should be
      interconnected via a 'global' electric network rather than the respective 'local'
      impedance. Once the uncoupled electric wave has the same wavelength and opposite
      group velocity as the uncoupled flexural wave, the desired coupled band gap
      emerges. The Wave Finite Element Method (WFEM) is used to investigate the
      evolution of the coupled band gap with respect to propagation direction and
      electric parameters. Further, the bandwidth and directionality of the coupled
      band gap are compared with the LR and Bragg gaps. An indicator termed ratio of
      single wave (RSW) is proposed to determine the effective band gap for a given
      deformation (electric, flexural, etc.). The features of the coupled band gap are
      validated by a forced response analysis. We show that the coupled band gap,
      despite directional, can be much wider than the LR gap with the same overall
      inductance. This might lead to an alternative to adaptively create band gaps.

PMID- 30205500
TI  - Face Detection in Nighttime Images Using Visible-Light Camera Sensors with Two
      Step Faster Region-Based Convolutional Neural Network.
AB  - Conventional nighttime face detection studies mostly use near-infrared (NIR)
      light cameras or thermal cameras, which are robust to environmental illumination
      variation and low illumination. However, for the NIR camera, it is difficult to
      adjust the intensity and angle of the additional NIR illuminator according to its
      distance from an object. As for the thermal camera, it is expensive to use as a
      surveillance camera. For these reasons, we propose a nighttime face detection
      method based on deep learning using a single visible-light camera. In a long
      distance night image, it is difficult to detect faces directly from the entire
      image due to noise and image blur. Therefore, we propose Two-Step Faster region
      based convolutional neural network (R-CNN) based on the image preprocessed by
      histogram equalization (HE). As a two-step scheme, our method sequentially
      performs the detectors of body and face areas, and locates the face inside a
      limited body area. By using our two-step method, the processing time by Faster R
      CNN can be reduced while maintaining the accuracy of face detection by Faster R
      CNN. Using a self-constructed database called Dongguk Nighttime Face Detection
      database (DNFD-DB1) and an open database of Fudan University, we proved that the
      proposed method performs better compared to other existing face detectors. In
      addition, the proposed Two-Step Faster R-CNN outperformed single Faster R-CNN and
      our method with HE showed higher accuracies than those without our preprocessing
      in nighttime face detection.

PMID- 30205502
TI  - Electromagnetic Shielding Effectiveness of Woven Fabrics with High Electrical
      Conductivity: Complete Derivation and Verification of Analytical Model.
AB  - In this paper, electromagnetic shielding effectiveness of woven fabrics with high
      electrical conductivity is investigated. Electromagnetic interference-shielding
      woven-textile composite materials were developed from a highly electrically
      conductive blend of polyester and the coated yarns of Au on a polyamide base. A
      complete analytical model of the electromagnetic shielding effectiveness of the
      materials with apertures is derived in detail, including foil, material with one
      aperture, and material with multiple apertures (fabrics). The derived analytical
      model is compared for fabrics with measurement of real samples. The key finding
      of the research is that the presented analytical model expands the shielding
      theory and is valid for woven fabrics manufactured from mixed and coated yarns
      with a value of electrical conductivity equal to and/or higher than sigma = 244
      S/m and an excellent electromagnetic shielding effectiveness value of 25-50 dB at
      0.03-1.5 GHz, which makes it a promising candidate for application in
      electromagnetic interference (EMI) shielding.

PMID- 30205503
TI  - Structural Diversity of Six Coordination Polymers Based on the Designed X-Shaped
      Ligand 1,1,1,1-Tetrakis[(3-pyridiniourea)methyl]methane.
AB  - In this study, six coordination polymers (CPs),
      {[Ag2(L)(CF3SO3)].CF3SO3.2H2O.DMF}n (1), {[Ag(L)].SbF6.4DMF.H2O}n (2),
      {[Zn(L)0.5(I)2].3.75H2O}n (3), {[Cd2(L)(I)4(H2O)(DMF)].4H2O.3DMF}n (4),
      {[Hg2(L)(I)4].H2O.4DMF}n (5) and {[Hg2(L)(Cl)4].2H2O.3DMF}n (6), were obtained
      based on the designed X-shaped urea-based ligand. X-ray single crystal
      diffraction analysis revealed that complex 1 displayed a 3D (3,4)-connected
      {6.82}{64.82}-tcj net. Complex 2 featured a 2D 4-connected {43.63} sheet.
      Complexes 3 and 5 exhibited a 1D polymeric loop chain. Complex 4 displayed a 1D
      polymeric fishbone chain. Complex 6 showed a 2D 4-connected {44.62}-sql sheet.
      Structural comparison revealed that not only the metal ions, but also the anions
      played crucial roles in the control of final structures.

PMID- 30205504
TI  - PEDOT:PSS-Based Temperature-Detection Thread for Wearable Devices.
AB  - In this research, we developed a wearable temperature-sensing element by dip
      dyeing threads in poly (3,4-ethylenedioxythiophene) polystyrene sulfonate
      (PEDOT:PSS) (p-type conducting polymer) solution. The PEDOT:PSS was used to dye
      the textile and it exhibited negative temperature coefficient characteristics in
      which the resistance decreases as the temperature increases. The fabricated
      temperature-detection thread achieved a sensitivity of 167.1 Omega/ degrees C
      with 99.8% linearity in the temperature range of -50  degrees C to 80  degrees C.
      We anticipate that temperature sensors that apply our technology will be made as
      stitch- or textile-type for wearable devices, and they will be widely adopted for
      different applications such as in fitness, leisure, healthcare, medical
      treatment, infotainment, industry, and military applications, among others.

PMID- 30205506
TI  - Transcriptome Signatures of Canine Mammary Gland Tumors and Its Comparison to
      Human Breast Cancers.
AB  - Breast cancer (BC)/mammary gland carcinoma (MGC) is the most frequently diagnosed
      and leading cause of cancer-related mortality in both women and canines. To
      better understand both canine MGC and human BC-specific genes, we sequenced RNAs
      obtained from eight pairs of carcinomas and adjacent normal tissues in dogs. By
      comprehensive transcriptome analysis, 351 differentially expressed genes (DEGs)
      were identified in overall canine MGCs. Based on the DEGs, comparative analysis
      revealed correlation existing among the three histological subtypes of canine MGC
      (ductal, simple, and complex) and four molecular subtypes of human BC (HER2+,
      ER+, ER&HER2+, and TNBC). Eight DEGs shared by all three subtypes of canine MGCs
      had been previously reported as cancer-associated genes in human studies. Gene
      ontology and pathway analyses using the identified DEGs revealed that the
      biological processes of cell proliferation, adhesion, and inflammatory responses
      are enriched in up-regulated MGC DEGs. In contrast, fatty acid homeostasis and
      transcription regulation involved in cell fate commitment were down-regulated in
      MGC DEGs. Moreover, correlations are demonstrated between upstream promoter
      transcripts and DEGs. Canine MGC- and subtype-enriched gene expression allows us
      to better understand both human BC and canine MGC, yielding new insight into the
      development of biomarkers and targets for both diseases.

PMID- 30205505
TI  - What's New in Gastric Cancer: The Therapeutic Implications of Molecular
      Classifications and Future Perspectives.
AB  - Despite some remarkable innovations and the advent of novel molecular
      classifications the prognosis of patients with advanced gastric cancer (GC)
      remains overall poor and current clinical application of new advances is
      disappointing. During the last years only Trastuzumab and Ramucirumab have been
      approved and currently used as standard of care targeted therapies, but the
      systemic management of advanced disease did not radically change in contrast with
      the high number of molecular drivers identified. The Cancer Genome Atlas (TCGA)
      and Asian Cancer Research Group (ACRG) classifications paved the way, also for
      GC, to that more contemporary therapeutic approach called "precision medicine"
      even if tumor heterogeneity and a complex genetic landscape still represent a
      strong barrier. The identification of specific cancer subgroups is also making
      possible a better selection of patients that are most likely to respond to
      immunotherapy. This review aims to critically overview the available molecular
      classifications summarizing the main druggable molecular drivers and their
      possible therapeutic implications also taking advantage of new technologies and
      acquisitions.

PMID- 30205509
TI  - Smartwatch User Interface Implementation Using CNN-Based Gesture Pattern
      Recognition.
AB  - In recent years, with an increase in the use of smartwatches among wearable
      devices, various applications for the device have been developed. However, the
      realization of a user interface is limited by the size and volume of the
      smartwatch. This study aims to propose a method to classify the user's gestures
      without the need of an additional input device to improve the user interface. The
      smartwatch is equipped with an accelerometer, which collects the data and learns
      and classifies the gesture pattern using a machine learning algorithm. By
      incorporating the convolution neural network (CNN) model, the proposed pattern
      recognition system has become more accurate than the existing model. The
      performance analysis results show that the proposed pattern recognition system
      can classify 10 gesture patterns at an accuracy rate of 97.3%.

PMID- 30205508
TI  - 2-Phenylacetamide Isolated from the Seeds of Lepidium apetalum and Its Estrogen
      Like Effects In Vitro and In Vivo.
AB  - The aim of this study was to investigate the estrogen-like effects of 2
      phenylacetamide (PA), which is the main compound isolated from the seeds of
      Lepidium apetalum Willd (LA). Results showed that LA and PA could promote the
      proliferation of MCF-7 cells. The mouse uterine weight test showed that, LA and
      PA could increase the uterus index of immature female mice, and the levels of
      luteinizing hormone (LH) and estrogen (E2). LA could increase the expression of
      ERalpha and ERbeta, while PA could increase the expression of ERalpha, ERbeta and
      GPR30 in the uterus and MCF-7 cells. In addition, co-incubation of the estrogen
      receptor blocker with LA or PA abolished the inductive effect of the
      proliferation. PA has estrogenic activities and was the material basis of LA that
      played the estrogenic effect. LA and PA might be used for the treatment of
      perimenopause syndrome in a novel application.

PMID- 30205507
TI  - Lead Compounds from Mangrove-Associated Microorganisms.
AB  - The mangrove ecosystem is considered as an attractive biodiversity hotspot that
      is intensively studied in the hope of discovering new useful chemical scaffolds,
      including those with potential medicinal application. In the past two decades,
      mangrove-derived microorganisms, along with mangrove plants, proved to be rich
      sources of bioactive secondary metabolites as exemplified by the constant rise in
      the number of publications, which suggests the great potential of this important
      ecological niche. The present review summarizes selected examples of bioactive
      compounds either from mangrove endophytes or from soil-derived mangrove fungi and
      bacteria, covering the literature from 2014 to March 2018. Accordingly, 163
      natural products are described in this review, possessing a wide range of potent
      bioactivities, such as cytotoxic, antibacterial, antifungal, alpha-glucosidase
      inhibitory, protein tyrosine phosphatase B inhibitory, and antiviral activities,
      among others.

PMID- 30205510
TI  - Hospital-Wide Surveillance of Healthcare-Associated Infections as a Source of
      Information about Specific Hospital Needs. A 5-Year Observation in a Multiprofile
      Provincial Hospital in the South of Poland.
AB  - Healthcare-associated infections (HAIs) are adverse complications of
      hospitalisation resulting in delayed recovery and increased costs. The aim of
      this study was an analysis of epidemiological factors obtained in the framework
      of constant, comprehensive (hospital-wide) infection registration, and
      identification of priorities and needs in infection control, both with regard to
      targeted surveillance, as well as preventative actions. The study was carried out
      according to the methodology recommended by the HAI-Net (Surveillance Network)
      coordinated by the European Centre for Disease Prevention and Control, in the
      multiprofile hospital in Southern Poland, between 2012 and 2016. A total of
      159,028 patients were under observation and 2184 HAIs were detected. The
      incidence was 1.4/100 admissions (2.7/1000 patient-das of hospitalisation) and
      significantly differed depending on the type of the patient care: in intensive
      care units (ICU) 16.9%; in surgical units, 1.3%; non-surgical units, 1.0%; and
      paediatric units, 1.8%. The most common HAI was gastrointestinal infections (GIs,
      28.9%), followed by surgical site infections (SSIs, 23.0%) and bloodstream
      infections (BSIs, 16.1%). The vast majority of GIs, BSIs, urinary tract
      infections, and incidents of pneumonia (PN) were detected in non-ICUs. As many as
      33.2% of cases of HAI were not confirmed microbiologically. The most frequently
      detected etiologic agent of infections was Clostridium difficile-globally and in
      GI (49%). Comprehensive analysis of the results allowed to identify important
      elements of surveillance of infections, i.e., surveillance of GI, PN, and BSI not
      only in ICU, but also in non-ICU wards, indicating a need for implementing rapid
      actions to improve compliance with HAI prevention procedures.

PMID- 30205511
TI  - Brazing of Mo to Glidcop Dispersion Strengthened Copper for Accelerating
      Structures.
AB  - Alumina dispersion-strengthened copper, Glidcop, is used widely in high-heat-load
      ultra-high-vacuum components for synchrotron light sources (absorbers),
      accelerator components (beam intercepting devices), and in nuclear power plants.
      Glidcop has similar thermal and electrical properties to oxygen free electrical
      (OFE) copper, but has superior mechanical properties, thus making it a feasible
      structural material; its yield and ultimate tensile strength are equivalent to
      those of mild-carbon steel. The purpose of this work has been to develop a
      brazing technique to join Glidcop to Mo, using a commercial Cu-based alloy. The
      effects of the excessive diffusion of the braze along the grain boundaries on the
      interfacial chemistry and joint microstructure, as well as on the mechanical
      performance of the brazed joints, has been investigated. In order to prevent the
      diffusion of the braze into the Glidcop alloy, a copper barrier layer has been
      deposited on Glidcop by means of RF-sputtering.

PMID- 30205512
TI  - Analysis of the Subdivision Errors of Photoelectric Angle Encoders and
      Improvement of the Tracking Precision of a Telescope Control System.
AB  - Photoelectric angle encoders, working as position sensors, have a great influence
      on the accuracy and stability of telescope control systems (TCS). In order to
      improve the tracking precision of TCS, a method based on subdivision error
      compensation for photoelectric angle encoders is proposed. First, a mathematical
      analysis of six types of subdivision errors (DC error, phase error, amplitude
      error, harmonic error, noise error, and quantization error) is presented, which
      is different from the previously used analysis based on the Lissajous figure
      method. In fact, we believe that a mathematical method is more efficient than the
      figure method for the expression of subdivision errors. Then, the distribution
      law and period length of each subdivision error are analyzed. Finally, an error
      compensation algorithm is presented. In a real TCS, the elevation jittering
      phenomenon occurs, which indicates that compensating for the amplitude error is
      necessary. A feed-forward loop is then introduced into the TCS, which is position
      loop- and velocity loop-closed, leading to a decrease of the tracking error by
      nearly 54.6%, from 2.31" to 1.05", with a leading speed of 0.25 degrees /s, and
      by 40.5%, from 3.01" to 1.79", with a leading speed of 1 degrees /s. This method
      can realize real-time compensation and improve the ability of TCS without any
      change of the hardware. In addition, independently of the environment and the
      kind of control strategy used, this method can also improve the tracking
      precision presumably because it compensates the measuring error inside the
      photoelectric angle encoder.

PMID- 30205513
TI  - Phosphorylation-Dependent Inhibition of Akt1.
AB  - Protein kinase B (Akt1) is a proto-oncogene that is overactive in most cancers.
      Akt1 activation requires phosphorylation at Thr308; phosphorylation at Ser473
      further enhances catalytic activity. Akt1 activity is also regulated via
      interactions between the kinase domain and the N-terminal auto-inhibitory
      pleckstrin homology (PH) domain. As it was previously difficult to produce Akt1
      in site-specific phosphorylated forms, the contribution of each activating
      phosphorylation site to auto-inhibition was unknown. Using a combination of
      genetic code expansion and in vivo enzymatic phosphorylation, we produced Akt1
      variants containing programmed phosphorylation to probe the interplay between
      Akt1 phosphorylation status and the auto-inhibitory function of the PH domain.
      Deletion of the PH domain increased the enzyme activity for all three
      phosphorylated Akt1 variants. For the doubly phosphorylated enzyme, deletion of
      the PH domain relieved auto-inhibition by 295-fold. We next found that
      phosphorylation at Ser473 provided resistance to chemical inhibition by Akti-1/2
      inhibitor VIII. The Akti-1/2 inhibitor was most effective against pAkt1T308 and
      showed four-fold decreased potency with Akt1 variants phosphorylated at Ser473.
      The data highlight the need to design more potent Akt1 inhibitors that are
      effective against the doubly phosphorylated and most pathogenic form of Akt1.

PMID- 30205514
TI  - Intrinsic Sensing Properties of Chrysotile Fiber Reinforced Piezoelectric Cement
      Based Composites.
AB  - Lead-zirconate-titanate (PZT) nanoscale powder was first synthesized by the sol
      gel method, then PZT and 0-3 type PZT/chrysotile fiber (CSF)/cement composite
      (PZTCC) wafers were fabricated after grind-mixing PZT powder with strontium
      carbonate and/or cement, ductile CSF in tandem with press-sintered process,
      respectively. The crystal structure (XRD), microstructure (SEM), piezoelectric
      properties after surface silver penetration, and polarization of the PZT and
      PZTCC wafer were investigated. Furthermore, self-sensing responses under either
      impulse or cyclic loading and micro-hardness toughness of PZTCC were also
      investigated. Results show that the incorporation of CSF and cement admixture
      weakens the perovskite crystalline peak of PZTCC; reduces the corresponding
      piezoelectric coefficient from 119.2 pC/N to 32.5 pC/N; but effectively bridges
      the gap on the toughness between PZTCC and concrete since the corresponding
      microhardness with 202.7 MPa of PZTCC is close to that of concrete. A good linear
      and fast electrical response against either impulse or cyclic loading of the
      PZTCC is achieved with their respective sensitivity, linearity, and repeatability
      to 1.505 mV/N, 2.42%, and 2.11%. The sensing responses and toughness of PZTCC is
      encouraging as an intrinsic piezoelectric sensor for real-time health monitoring
      of ductile concrete structures.

PMID- 30205515
TI  - Efficient Interference Estimation with Accuracy Control for Data-Driven Resource
      Allocation in Cloud-RAN.
AB  - The emerging edge computing paradigm has given rise to a new promising mobile
      network architecture, which can address a number of challenges that the operators
      are facing while trying to support growing end user's needs by shifting the
      computation from the base station to the edge cloud computing facilities. With
      such powerfully computational power, traditional unpractical resource allocation
      algorithms could be feasible. However, even with near optimal algorithms, the
      allocation result could still be far from optimal due to the inaccurate modeling
      of interference among sensor nodes. Such a dilemma calls for a measurement data
      driven resource allocation to improve the total capacity. Meanwhile, the
      measurement process of inter-nodes' interference could be tedious, time-consuming
      and have low accuracy, which further compromise the benefits brought by the edge
      computing paradigm. To this end, we propose a measurement-based estimation
      solution to obtain the interference efficiently and intelligently by dynamically
      controlling the measurement and estimation through an accuracy-driven model.
      Basically, the measurement cost is reduced through the link similarity model and
      the channel derivation model. Compared to the exhausting measurement method, it
      can significantly reduce the time cost to the linear order of the network size
      with guaranteed accuracy through measurement scheduling and the accuracy control
      process, which could also balance the tradeoff between accuracy and measurement
      overhead. Extensive experiments based on real data traces are conducted to show
      the efficiency of the proposed solutions.

PMID- 30205516
TI  - NFKB1 and Cancer: Friend or Foe?
AB  - Current evidence strongly suggests that aberrant activation of the NF-kappaB
      signalling pathway is associated with carcinogenesis. A number of key cellular
      processes are governed by the effectors of this pathway, including immune
      responses and apoptosis, both crucial in the development of cancer. Therefore, it
      is not surprising that dysregulated and chronic NF-kappaB signalling can have a
      profound impact on cellular homeostasis. Here we discuss NFKB1 (p105/p50), one of
      the five subunits of NF-kappaB, widely implicated in carcinogenesis, in some
      cases driving cancer progression and in others acting as a tumour-suppressor. The
      complexity of the role of this subunit lies in the multiple dimeric combination
      possibilities as well as the different interacting co-factors, which dictate
      whether gene transcription is activated or repressed, in a cell and organ
      specific manner. This review highlights the multiple roles of NFKB1 in the
      development and progression of different cancers, and the considerations to make
      when attempting to manipulate NF-kappaB as a potential cancer therapy.

PMID- 30205519
TI  - MEMS Gyroscope Automatic Real-Time Mode-Matching Method Based on Phase-Shifted 45
      degrees  Additional Force Demodulation.
AB  - In order to solve the problem where existing mode-matching methods in
      microelectromechanical systems (MEMS) vibrating gyroscopes fail to meet real-time
      and reliability requirements, this paper presents a novel method to accomplish
      automatic and real-time mode-matching based on phase-shifted 45 degrees 
      additional force demodulation (45 degrees  AFD-RM). The phase-shifted 45 degrees 
      additional force signal has the same frequency as the quadrature force signal,
      but it is phase-shifted by 45 degrees  and applied to the sense mode. In
      addition, two-way phase-shifted 45 degrees  demodulations are used at the sense
      mode detection output to obtain a phase metric that is independent of the
      Coriolis force and can reflect the mode-matching state. Then, this phase metric
      is used as a control variable to adaptively control the tuning voltage, so as to
      change the sense-mode frequency through the negative stiffness effect and
      ultimately achieve real-time mode-matching. Simulation and experimental results
      show that the proposed 45 degrees  AFD-RM method can achieve real-time matching.
      The mode frequency split is controlled within 0.1 Hz, and the gyroscope scale
      factor, zero-bias instability, and angle random walk are effectively improved.

PMID- 30205520
TI  - On Molecular Descriptors of Carbon Nanocones.
AB  - Many degree-based topological indices can be obtained from the closed-off M
      polynomial of a carbon nanocone. These topological indices are numerical
      parameters that are associated with a structure and, in combination, determine
      the properties of the carbon nanocone. In this paper, we compute the closed form
      of the M-polynomial of generalized carbon nanocone and recover many important
      degree-based topological indices. We use software Maple 2015 (Maplesoft,
      Waterloo, ON, Canada) to plot the surfaces and graphs associated with these
      nanocones, and relate the topological indices to the structure of these
      nanocones.

PMID- 30205517
TI  - Genome-Wide Identification of PIFs in Grapes (Vitis vinifera L.) and Their
      Transcriptional Analysis under Lighting/Shading Conditions.
AB  - Phytochrome-interacting factors (PIFs), as the basic helix-loop-helix (bHLH)
      transcription factors, are the primary signaling partners for phytochromes (PHY)
      that play a key role in PHY-mediated light signal transduction. At present, there
      are few studies on PIFs in fruit trees. In order to clarify the status of PIFs in
      grapevines, we identified members of the grape PIFs family and conducted
      phylogenetic and expression analysis. We identified PIF1, PIF3, PIF4, and PIF7 in
      PIFs families of the grapevine (Vitis vinifera L.), which were distributed on
      four different chromosomes with similar gene structures. Except for the closer
      relationship with PIF1 of citrus, PIFs of grape were distant from the other fruit
      species such as apple, pear, peach, and strawberry. The VvPIFs (except VvPIF4)
      were located in the syntenic block with those from Arabidopsisthaliana, Solanum
      lycopersicum, or Citrus sinensis. In addition to PIF1, all PIFs in grapevines
      have conserved active PHYB binding (APB) sequences. VvPIF1 has a conserved PIF1
      specific active PHYA binding (APA) sequence, while amino acid mutations occurred
      in the specific APA sequence in VvPIF3. Interestingly, two specific motifs were
      found in the PIF4 amino acid sequence. The photoreceptor-related elements in the
      VvPIFs promoter region were the most abundant. PIF1, LONG HYPOCOTYL 5 (HY5) and
      PIF3, PIF4, GIBBERELLIC ACID INSENSITIVE 1 (GAI1) may interact with each other
      and participate together in light signal transduction. The relative expression
      levels of the VvPIFs showed diverse patterns in the various organs at different
      developmental stages, of which PIF4 was most highly expressed. Prior to
      maturation, the expression of PIF4 and PIF7 in the skin of the different
      cultivars increased, while the expression of all PIFs in the flesh decreased. The
      transcription level of PIFs in grape leaves was sensitive to changes in lighting
      and shading. Shading treatment was beneficial for enhancing the transcription
      level of VvPIFs, but the effect on VvPIF3 and VvPIF4 was time-controlled. We
      concluded that PIFs in grapevines are both conservative and species-specific. The
      identification and analysis of grape PIFs could provide a theoretical foundation
      for the further construction of grape light regulation networks.

PMID- 30205518
TI  - Improved Immune Responses Against Zika Virus After Sequential Dengue and Zika
      Virus Infection in Humans.
AB  - The high levels of dengue-virus (DENV) seroprevalence in areas where the Zika
      virus (ZIKV) is circulating and the cross-reactivity between these two viruses
      have raised concerns on the risk of increased ZIKV disease severity for patients
      with a history of previous DENV infections. To determine the role of DENV
      preimmunity in ZIKV infection, we analyzed the T- and B-cell responses against
      ZIKV in donors with or without previous DENV infection. Using peripheral blood
      mononuclear cells (PBMCs) from donors living in an endemic area in Colombia, we
      have identified, by interferon (IFN)-gamma enzyme-linked immunospot (ELISPOT)
      assay, most of the immunodominant ZIKV T-cell epitopes in the nonstructural (NS)
      proteins NS1, NS3, and NS5. Analyses of the T- and B-cell responses in the same
      donors revealed a stronger T-cell response against peptides conserved between
      DENV and ZIKV, with a higher level of ZIKV-neutralizing antibodies in DENV-immune
      donors in comparison with DENV-naive donors. Strikingly, the potential for
      antibody-mediated enhancement of ZIKV infection was reduced in donors with
      sequential DENV and ZIKV infection in comparison with donors with DENV infection
      only. Altogether, these data suggest that individuals with DENV immunity present
      improved immune responses against ZIKV.

PMID- 30205521
TI  - Negative Cellular Effects of Urban Particulate Matter on Human Keratinocytes Are
      Mediated by P38 MAPK and NF-kappaB-dependent Expression of TRPV 1.
AB  - Urban particulate matter (UPM) exerts negative effects on various human organs.
      Transient receptor potential vanilloid 1 (TRPV1) is a polymodal sensory
      transducer that can be activated by multiple noxious stimuli. This study aimed to
      explore the effects of the UPM 1648a on the expression of TRPV1, and its
      regulatory mechanisms in HaCaT cells. UPM enhanced TRPV 1 promoter-luciferase
      reporter activity. UPM also increased expression of the TRPV 1 gene as evidenced
      by increased mRNA and protein levels of TRPV 1. In addition, elucidation of the
      underlying mechanism behind the UPM-mediated effects on TRPV 1 expression
      revealed that UPM can upregulate expression of the TRPV1 gene by activating
      activator protein-1 (AP-1) and nuclear factor kappa B (NF-kappaB). The UPM
      treatment also altered Ca2+ influx and cell proliferation, as well as production
      of interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-alpha), and interleukin
      1beta (IL-1beta). In addition, these UPM-induced effects were attenuated by
      SB203580 and ammonium pyrrolidinedithiocarbamate (PDTC). However, SP600125 and
      PD98059 did not alter the UPM-induced effects. Taken together, these findings
      indicate that UPM upregulates expression of the TRPV 1 gene, which is mediated by
      the p38 mitogen-activated protein kinase (MAPK) and NF-kappaB signaling pathways
      and suggest that UPM is a potential irritant that can induce skin processes such
      as aging and inflammatory responses.

PMID- 30205522
TI  - Added Sugars and Low- and No-Calorie Sweeteners in a Representative Sample of
      Food Products Consumed by the Spanish ANIBES Study Population.
AB  - Low- and no-calorie sweeteners (LNCS), intensely sweet compounds that virtually
      contain no calories, are used to replace added sugars in food and drinks.
      Knowledge about different LNCS data in Spanish foods and added sugar sources in
      Spain is limited, therefore our aim was to identify and compare their presence
      across main food groups consumed. Food and beverage products (n = 434) were
      obtained from the ANIBES Study (anthropometric data, macronutrients and
      micronutrients intake, practice of physical activity, socioeconomic data and
      lifestyles), a cross-sectional study of a representative sample of the Spanish
      population (9-75 years old; n = 2009) carried out in 2013. Food records were
      obtained from a three-day dietary record using a tablet device. Label data from
      1,164 products of different brands were collected and reviewed for content of
      added sugars and LNCS. LNCS were present in diet soft drinks (100%), "other
      sweets" (89%), soya drinks (45%), and yogurt and fermented milks (18%). Added
      sugars were present mainly in sugar soft drinks (100%), energy drinks (96%),
      sports drinks (96%), bakery and pastry (100%), chocolates (100%), ice cream
      (100%), breakfast cereals/bars (96%) and jams (89%). Main LNCS were acesulfame K,
      aspartame, cyclamate and sucralose. Sucrose, dextrose, glucose-fructose syrup,
      caramel and honey were the main added sugars. Our results show the diversity of
      foods groups including these ingredients. These data are not compiled in food
      composition databases, which should be periodically updated to include LNCS and
      added sugars to facilitate their assessment and monitoring in nutritional
      surveys.

PMID- 30205525
TI  - Damage Detection in Active Suspension Bridges: An Experimental Investigation.
AB  - This paper considers a Hilbert marginal spectrum-based approach to health
      monitoring of active suspension bridge hangers. The paper proposes to takes
      advantage of the presence of active cables and use them as an excitation mean of
      the bridge, while they are used for active damping. The Hilbert-Huang transform
      is used to calculate the Hilbert marginal spectrum and establish a damage index
      for each hanger of the suspension bridge. The paper aims to investigate the
      method experimentally, through a series of damage scenarios, on a laboratory
      suspension bridge mock-up equipped with four active cables; each active cable is
      made of a displacement actuator collocated with a force sensor. Different
      locations and levels of damage severity are implemented. For the first time, the
      investigation demonstrates experimentally the effectiveness of the technique, as
      well as its limitations, to detect and locate the damage in hangers of a
      suspension bridge.

PMID- 30205523
TI  - In the Heart of the Amazon: Noncommunicable Diseases and Apolipoprotein E4
      Genotype in the Riverine Population.
AB  - The Amazon River basin is the largest tropical forest in the world. Most of the
      Amazon belongs to Brazil, a developing country that currently faces huge
      challenges related to the consolidation of its universal healthcare system.
      Noncommunicable diseases (NCDs) are the leading cause of death in Brazil,
      accounting for 74% of all deaths, and NCDs are probably underestimated in
      Amazonian population because of their geographical isolation and the
      precariousness of riverine communities. Important risk factors, such as genetic
      susceptibility, remain undetermined in the riverine population. This study
      performed fasting blood sugar (FBS) and blood pressure measurements and
      investigated the presence of the epsilon4 allele of apolipoprotein E (APOE4) to
      determine the prevalence of diabetes, hypertension and the genetic risk of NCDs.
      FBS and APOE4 were measured in blood samples from 763 participants using
      spectrometry and real-time PCR; 67.5% showed altered measurements, and 57.9% had
      never been diagnosed or treated. Altered FBS was found in 28.3% of the
      participants, hypertension in 57.6% and APOE4 in 32.0%. The health profile of the
      riverine population appears to differ from that of urban population in the
      Amazon. Additional risk factors for NCDs, such as environmental contamination and
      nutritional transition, may contribute more than increased genetic susceptibility
      to the prevalence of altered FBS and hypertension. Our results will help guide
      the development of preventive strategies and governmental actions for more
      effective management of NCDs in the Amazon area.

PMID- 30205524
TI  - A Synthetic Peptide AWRK6 Alleviates Lipopolysaccharide-Induced Liver Injury.
AB  - During lipopolysaccharide (LPS)-induced sepsis, the liver plays central roles in
      toxins phagocytosis and clearance to protect the whole body. The liver cells were
      constantly irritated by LPS which leads to liver injury. While most anti-LPS
      agents showed little clinical activity against LPS-induced liver injury. Here,
      the protective effects of the synthetic peptide AWRK6 against LPS-induced liver
      injury have been investigated in vivo and in vitro. In mice liver homogenate, LPS
      administration elevated ALT (alanine aminotransferase), iNOS (inducible nitric
      oxide synthase) and repressed SOD (superoxide dismutase) activities and these
      changes were remarkably reversed by AWRK6. Histologically, AWRK6 effectively
      alleviated the histological changes and repressed LPS-induced neutrophils
      infiltration. By TUNEL assay on liver sections, AWRK6 was proven to inhibit
      apoptosis induced by LPS in mice livers, which was also verified by the protein
      levels of cleaved-caspase 9, Bax and Bcl-2. In addition, by in vitro study using
      HepG2 cells, AWRK6 was found to recover the LPS-reduced cell viability and reduce
      LPS-induced apoptosis. For mechanisms, AWRK6 was demonstrated to alleviate the
      LPS-induced phosphorylation of ERK, JNK and p38 MAPK, indicating the involvement
      of MAPKs in the protection of AWRK6 against liver injury. In summary, we have
      found the synthetic peptide AWRK6 as a promising novel agent for LPS-induced
      liver injury, by inhibiting cell apoptosis through MAPK signaling pathways, which
      might bring new strategies for the treatment of acute and chronic liver injuries.

PMID- 30205526
TI  - Field Evaluation of N95 Filtering Facepiece Respirators on Construction Jobsites
      for Protection against Airborne Ultrafine Particles.
AB  - Exposure to high concentrations of airborne ultrafine particles in construction
      jobsites may play an important role in the adverse health effects among
      construction workers, therefore adequate respiratory protection is required. The
      performance of particulate respirators has never been evaluated in field
      conditions against ultrafine particles on construction jobsites. In this study,
      respiratory protection levels against ultrafine particles of different size
      ranges were assessed during three common construction related jobs using a
      manikin-based set-up at 85 L/min air flow rate. Two NanoScan SMPS nanoparticle
      counters were utilized for measuring ultrafine particles in two sampling lines of
      the test filtering facepiece respirator-one from inside the respirator and one
      from outside the respirator. Particle size distributions were characterized using
      the NanoScan data collected from outside of the respirator. Two models of N95
      respirators were tested-foldable and pleated. Collected data indicate that
      penetration of all categories of ultrafine particles can exceed 5% and smaller
      ultrafine particles of <36.5 nm size generally penetrated least. Foldable N95
      filtering facepiece respirators were found to be less efficient than pleated N95
      respirators in filtering nanoparticles mostly at the soil moving site and the
      wooden building frameworks construction site. Upon charge neutralization by
      isopropanol treatment, the ultrafine particles of larger sizes penetrated more
      compared to particles of smaller sizes. Our findings, therefore, indicate that
      N95 filtering facepiece respirators may not provide desirable 95% protection for
      most categories of ultrafine particles and generally, 95% protection is
      achievable for smaller particles of 11.5 to 20.5 nm sizes. We also conclude that
      foldable N95 respirators are less efficient than pleated N95 respirators in
      filtering ultrafine particles, mostly in the soil moving site and the wooden
      building framework construction site.

PMID- 30205527
TI  - Sensing Characteristics of Tilted Long Period Fiber Gratings Inscribed by
      Infrared Femtosecond Laser.
AB  - We propose a novel tilted long period fiber grating (TLPFG) design, inscribed
      using a line-by-line inscription technique and an infrared femtosecond (Fs)
      laser. The responses of this TLPFG to external refractive index, temperature,
      torsion, and strain were systematically investigated to determine its sensing
      characteristics. The external refractive index (RI) was measured to be -602.86
      nm/RIU at an RI of ~1.432. The TLPFG was used to accurately measure temperatures
      up to 450  degrees C with a sensitivity of 103.8 pm/ degrees C. The torsion and
      strain sensitivity of the device were 48.94 nm/(rad/mm) and -0.63 pm/uepsilon,
      respectively. These results demonstrate that the proposed TLPFG could be used as
      sensors in a series of application fields including high temperatures and
      external environments.

PMID- 30205528
TI  - Reducing Stress and Promoting Social Integration of International Medical
      Students through a Tandem Program: Results of a Prospective-Program Evaluation.
AB  - Medical students, and especially international medical students (IMS), have been
      shown to experience more psychological distress than the general student
      population in Germany. In order to address these issues, a structured Tandem
      Program (TP) to reduce stress and foster social integration of IMS has been
      introduced at the Medical Faculty of Tuebingen. The Tandem Program was evaluated
      prospectively with perceived stress (PSQ-20) as the main outcome. Secondary
      outcomes were 'motives to participate' in the TP, 'specific stressors', and
      'experiences made' during the program. Stress levels of IMS at the beginning of
      the program (t0) (M = 48.14, SD = 11.95) were higher than those of German
      participants (M = 39.33, SD = 8.31) (t (67) = -3.66, p < 0.001). At the end of
      the TP (t1), stress levels of international students were significantly lower
      than at t0. "Improved ability to work in a team" was seen as one of the most
      beneficial factors. The results indicate that tandem programs at medical
      faculties may be a promising curricular intervention towards reducing stress
      levels, improving integration of international students, and to enhance
      intercultural and team-oriented competencies in both international and national
      medical students.

PMID- 30205529
TI  - Impact of Tumor Regression Grade as a Major Prognostic Factor in Locally Advanced
      Rectal Cancer after Neoadjuvant Chemoradiotherapy: A Proposal for a Modified
      Staging System.
AB  - There is ongoing debate regarding the significance of complete or near-complete
      response after neoadjuvant chemoradiotherapy (CRT) for rectal cancer. This study
      assessed the prognostic value of the Dworak tumor regression grade (TRG)
      following neoadjuvant CRT and surgery primarily in patients with pathological
      stage (ypStage) II and III rectal cancer. The records of 331 patients who
      underwent neoadjuvant CRT followed by total mesorectal excision between 2004 and
      2015 were retrospectively reviewed. Patients were categorized as having a good
      response (GR, TRG 3/4, n = 122) or a poor response (PR, TRG 1/2, n = 209). At a
      median follow-up of 65 months, five-year disease-free survival (DFS) was higher
      in the GR group than in the PR group (91.3% vs. 66.6%, p < 0.001). Patients with
      a GR and ypStage II disease had a five-year DFS that was indistinguishable from
      that of patients with ypStage 0-I disease (92.3% vs. 90.7%, p = 0.885). Likewise,
      patients with a GR and ypStage III disease had a five-year DFS similar to those
      with ypStage II disease (76.0% vs. 75.9%, p = 0.789). A new modified staging
      system that incorporates grouped TRG (GR vs. PR) was developed. The prognostic
      performance of this modified stage and the ypStage was compared with the Harrell
      C statistic. C statistic of the modified stage was higher than that of the
      ypStage (0.784 vs. 0.757, p = 0.012). The results remained robust after
      multivariate Cox regression analyses. In conclusion, a GR to neoadjuvant CRT is
      an independent predictor of good DFS and overall survival and further stratifies
      patients so as to estimate the risk of recurrence and survival among patients
      with ypStage II and III rectal cancer.

PMID- 30205531
TI  - A Novel Tri-Axial MEMS Gyroscope Calibration Method over a Full Temperature
      Range.
AB  - The micro-electro-mechanical inertial measurement unit (MEMS-IMU) has gradually
      become a research hotspot in the field of mid-low navigation, because of its
      advantages of low cost, small size, light weight, and low power consumption
      (CSWap). However, the performance of MEMS-IMUs can be severely degraded when
      subjected to temperature changes, especially gyroscopes. In order to make full
      use of the navigation accuracy, this paper proposes an optimized error
      calibration method for a tri-axial MEMS gyroscope across a full temperature
      range. First of all, a calibration error model is established which includes
      package misalignment error, sensor-to-sensor non-orthogonality error, scale
      factor, and bias. Then, a simple three-position positive/reversed test is
      undertaken by carrying out a single-axis temperature-controlled turntable at
      different reference temperature points. Lastly, the error compensation vector is
      obtained using the least squares method to establish an error matrix. It is worth
      mentioning that the error compensation vector at a known temperature point can be
      calculated through Lagrange interpolation; then, the outputs of the tri-axial
      MEMS gyroscope can be well compensated, eliminating the need for a recalibration
      step. The experimental results confirm the effectiveness of the proposed method,
      which is feasible and operational in engineering applications, and has a certain
      reference value.

PMID- 30205530
TI  - Nutrition Impact Symptoms Are Prognostic of Quality of Life and Mortality after
      Surgery for Oesophageal Cancer.
AB  - We aimed to clarify the influence of nutritional problems after surgery for
      oesophageal cancer on functional health related quality of life (HRQOL) and
      survival. A prospective nationwide cohort of oesophageal cancer patients operated
      2001-2005 in Sweden with 6 months postoperative follow up was used. Nutritional
      problems were categorized as low/moderate/severe/very severe based on weight loss
      and nutrition impact symptoms. An ANCOVA model calculated mean score differences
      (MD) with 95% confidence intervals (CI) of global quality of life (QOL), social
      and physical function scores, stratified by preoperative body mass index (BMI)
      <25 and >=25. A Cox proportional hazards model produced hazard ratios (HR) with
      95% CI for overall 5-year survival. Of 358 patients, 196 (55%) had preoperative
      BMI >=25. Very severe and severe nutritional problems were associated with worse
      HRQOL in both BMI groups. E.g. MD's for global QOL among 'very severe' group was 
      29 (95% CI -39--19) and -20 (95% CI -29--11) for <25 and >=25 BMI, respectively,
      compared to the 'low' group. Overall 5-year survival among 'very severe' and BMI
      >= 25 was worse; HR 4.6 (95% CI 1.4-15.6). Intense nutritional problems
      negatively impact postoperative HRQOL and combined with preoperative BMI >= 25
      are associated with poorer 5-year overall survival representing a group needing
      greater clinical attention.

PMID- 30205532
TI  - Capsid Structure of dsRNA Fungal Viruses.
AB  - Most fungal, double-stranded (ds) RNA viruses lack an extracellular life cycle
      stage and are transmitted by cytoplasmic interchange. dsRNA mycovirus capsids are
      based on a 120-subunit T = 1 capsid, with a dimer as the asymmetric unit. These
      capsids, which remain structurally undisturbed throughout the viral cycle,
      nevertheless, are dynamic particles involved in the organization of the viral
      genome and the viral polymerase necessary for RNA synthesis. The atomic structure
      of the T = 1 capsids of four mycoviruses was resolved: the L-A virus of
      Saccharomyces cerevisiae (ScV-L-A), Penicillium chrysogenum virus (PcV),
      Penicillium stoloniferum virus F (PsV-F), and Rosellinia necatrix quadrivirus 1
      (RnQV1). These capsids show structural variations of the same framework, with 60
      asymmetric or symmetric homodimers for ScV-L-A and PsV-F, respectively, monomers
      with a duplicated similar domain for PcV, and heterodimers of two different
      proteins for RnQV1. Mycovirus capsid proteins (CP) share a conserved alpha
      helical domain, although the latter may carry different peptides inserted at
      preferential hotspots. Insertions in the CP outer surface are likely associated
      with enzymatic activities. Within the capsid, fungal dsRNA viruses show a low
      degree of genome compaction compared to reoviruses, and contain one to two copies
      of the RNA-polymerase complex per virion.

PMID- 30205533
TI  - In Vitro Studies on Zinc Binding and Buffering by Intestinal Mucins.
AB  - The investigation of luminal factors influencing zinc availability and
      accessibility in the intestine is of great interest when analyzing parameters
      regulating intestinal zinc resorption. Of note, intestinal mucins were suggested
      to play a beneficial role in the luminal availability of zinc. Their exact zinc
      binding properties, however, remain unknown and the impact of these glycoproteins
      on human intestinal zinc resorption has not been investigated in detail. Thus,
      the aim of this study is to elucidate the impact of intestinal mucins on luminal
      uptake of zinc into enterocytes and its transfer into the blood. In the present
      study, in vitro zinc binding properties of mucins were analyzed using
      commercially available porcine mucins and secreted mucins of the goblet cell line
      HT-29-MTX. The molecular zinc binding capacity and average zinc binding affinity
      of these glycoproteins demonstrates that mucins contain multiple zinc-binding
      sites with biologically relevant affinity within one mucin molecule. Zinc uptake
      into the enterocyte cell line Caco-2 was impaired by zinc-depleted mucins. Yet
      this does not represent their form in the intestinal lumen in vivo under zinc
      adequate conditions. In fact, zinc-uptake studies into enterocytes in the
      presence of mucins with differing degree of zinc saturation revealed zinc
      buffering by these glycoproteins, indicating that mucin-bound zinc is still
      available for the cells. Finally, the impact of mucins on zinc resorption using
      three-dimensional cultures was studied comparing the zinc transfer of a Caco-2/HT
      29-MTX co-culture and conventional Caco-2 monoculture. Here, the mucin secreting
      co-cultures yielded higher fractional zinc resorption and elevated zinc transport
      rates, suggesting that intestinal mucins facilitate the zinc uptake into
      enterocytes and act as a zinc delivery system for the intestinal epithelium.

PMID- 30205536
TI  - Distributed Space Debris Tracking with Consensus Labeled Random Finite Set
      Filtering.
AB  - Space debris tracking is a challenge for spacecraft operation because of the
      increasing number of both satellites and the amount of space debris. This paper
      investigates space debris tracking using marginalized delta -generalized labeled
      multi-Bernoulli filtering on a network of nodes consisting of a collection of
      sensors with different observation volumes. A consensus algorithm is used to
      achieve the global average by iterative regional averages. The sensor network can
      have unknown or time-varying topology. The proposed space debris tracking
      algorithm provides an efficient solution to the key challenges (e.g., detection
      uncertainty, data association uncertainty, clutter, etc.) for space situational
      awareness. The performance of the proposed algorithm is verified by simulation
      results.

PMID- 30205534
TI  - Recent Selection on a Class I ADH Locus Distinguishes Southwest Asian Populations
      Including Ashkenazi Jews.
AB  - The derived human alcohol dehydrogenase (ADH)1B*48His allele of the ADH1B
      Arg48His polymorphism (rs1229984) has been identified as one component of an East
      Asian specific core haplotype that underwent recent positive selection. Our study
      has been extended to Southwest Asia and additional markers in East Asia. Fst
      values (Sewall Wright's fixation index) and long-range haplotype analyses
      identify a strong signature of selection not only in East Asian but also in
      Southwest Asian populations. However, except for the ADH2B*48His allele,
      different core haplotypes occur in Southwest Asia compared to East Asia and the
      extended haplotypes also differ. Thus, the ADH1B*48His allele, as part of a core
      haplotype of 10 kb, has undergone recent rapid increases in frequency
      independently in the two regions after divergence of the respective populations.
      Emergence of agriculture may be the common factor underlying the evident
      selection.

PMID- 30205535
TI  - Removal Characteristics of N-Nitrosamines and Their Precursors by Pilot-Scale
      Integrated Membrane Systems for Water Reuse.
AB  - This study investigated the removal characteristics of N-Nitrosamines and their
      precursors at three pilot-scale water reclamation plants. These plants applies
      different integrated membrane systems: (1) microfiltration (MF)/nanofiltration
      (NF)/reverse osmosis (RO) membrane; (2) sand filtration/three-stage RO; and (3)
      ultrafiltration (UF)/NF and UF/RO. Variable removal of N-Nitrosodimethylamine
      (NDMA) by the RO processes could be attributed to membrane fouling and the feed
      water temperature. The effect of membrane fouling on N-Nitrosamine removal was
      extensively evaluated at one of the plants by conducting one month of operation
      and chemical cleaning of the RO element. Membrane fouling enhanced N-Nitrosamine
      removal by the pilot-scale RO process. This finding contributes to better
      understanding of the variable removal of NDMA by RO processes. This study also
      investigated the removal characteristics of N-Nitrosamine precursors. The NF and
      RO processes greatly reduced NDMA formation potential (FP), but the UF process
      had little effect. The contributions of MF, NF, and RO processes for reducing FPs
      of NDMA, N-Nitrosopyrrolidine and N-Nitrosodiethylamine were different,
      suggesting different size distributions of their precursors.

PMID- 30205539
TI  - What Explains Education Disparities in Screening Mammography in the United
      States? A Comparison with The Netherlands.
AB  - Background: In the U.S., less educated women are substantially less likely to
      receive screening mammography. It is not clear whether this is due to differences
      in access to screening or in perceptions of breast cancer risks and the
      effectiveness of screening. We weigh the plausibility of these two explanations
      by examining how the dependence of mammography on education changes after
      conditioning on indicators of access and perceptions. We also compare estimates
      for the U.S. with those for the Netherlands where there is universal access to a
      publicly financed screening program. Method: Cross-sectional and cross-country
      comparable individual level data from the American Life Panel (n = 646) and the
      Netherlands Longitudinal Internet Studies for the Social Sciences (n = 1398) were
      used to estimate and explain education disparities in screening mammograms given
      to American and Dutch women aged 40+. The education gradient was estimated using
      logit models. Controls were sequentially added to detect whether disparities were
      explained by differences in access or perceptions of risks and effectiveness.
      Results: In the United States, high school graduates were 11.5 percentage points
      (95% CI: 1-22 percentage points) less likely than college graduates to receive a
      screening mammogram in the previous two years. This education gradient was
      largely explained by differences in income, insurance coverage and receipt of
      medical advice. It was not explained by educational differences in the perceived
      risk of breast cancer and the effectiveness of mammography. There were no
      education disparities in receipt of mammography among Dutch women within the 50
      75 age range covered by the national screening program. Conclusion: In the
      absence of a universal screening program in the U.S., determinants of access
      income, insurance coverage and receipt of medical advice-appear to drive the
      education disparities in screening mammography.

PMID- 30205537
TI  - Molecular Characterization of Near Full-Length Genomes of Hepatitis B Virus
      Isolated from Predominantly HIV Infected Individuals in Botswana.
AB  - The World Health Organization plans to eliminate hepatitis B and C Infections by
      2030. Therefore, there is a need to study and understand hepatitis B virus (HBV)
      epidemiology and viral evolution further, including evaluating occult (HBsAg
      negative) HBV infection (OBI), given that such infections are frequently
      undiagnosed and rarely treated. We aimed to molecularly characterize HBV genomes
      from 108 individuals co-infected with human immunodeficiency virus (HIV) and
      chronic hepatitis B (CHB) or OBI identified from previous HIV studies conducted
      in Botswana from 2009 to 2012. Full-length (3.2 kb) and nearly full-length (~3
      kb) genomes were amplified by nested polymerase chain reaction (PCR). Sequences
      from OBI participants were compared to sequences from CHB participants and
      GenBank references to identify OBI-unique mutations. HBV genomes from 50 (25 CHB
      and 25 OBI) individuals were successfully genotyped. Among OBI participants,
      subgenotype A1 was identified in 12 (48%), D3 in 12 (48%), and E in 1 (4%). A
      similar genotype distribution was observed in CHB participants. Whole HBV genome
      sequences from Botswana, representing OBI and CHB, were compared for the first
      time. There were 43 OBI-unique mutations, of which 26 were novel. Future studies
      using larger sample sizes and functional analysis of OBI-unique mutations are
      warranted.

PMID- 30205538
TI  - Correction of Hyponatremia May Be a Treatment Stratification Biomarker: A Two
      Stage Systematic Review and Meta-Analysis.
AB  - Changes in serum sodium concentration ([Na+]serum) can permit evaluation of the
      treatment effect of vasopressin antagonists (vaptans) in patients with worsening
      heart failure (HF) or cirrhotic ascites; that is, they may act as a treatment
      stratification biomarker. A two-stage systematic review and meta-analysis were
      carried out and contextualized by experts in fluid resuscitation and
      translational pharmacology (registration ID in the International Prospective
      Register of Systematic Reviews (PROSPERO): CRD42017051440). Meta-analysis of
      aggregated dichotomous outcomes was performed. Pooled estimates for correction of
      hyponatremia (normalization or an increase in [Na+]serum of at least 3-5 mEq/L)
      under treatment with vaptans (Stage 1) and for clinical outcomes in both
      worsening HF (rehospitalization and/or death) and cirrhotic ascites (ascites
      worsening) when correction of hyponatremia is achieved (Stage 2) were calculated.
      The body of evidence was assessed. Correction of hyponatremia was achieved under
      vaptans (odds ratio (OR)/95% confidence interval (95% CI)/I2/number of studies
      (n): 7.48/4.95-11.30/58%/15). Clinical outcomes in both worsening HF and
      cirrhotic ascites improved when correction of hyponatremia was achieved (OR/95%
      CI/I2/n: 0.51/0.26-0.99/52%/3). Despite the appropriateness of the study design,
      however, there are too few trials to consider that correction of hyponatremia is
      a treatment stratification biomarker. Patients with worsening HF or with
      cirrhotic ascites needing treatment with vaptans, have better clinical outcomes
      when correction of hyponatremia is achieved. However, the evidence base needs to
      be enlarged to propose formally correction of hyponatremia as a new treatment
      stratification biomarker. Markers for use with drugs are needed to improve
      outcomes related to the use of medicines.

PMID- 30205540
TI  - The Dirt on Clean Eating: A Cross Sectional Analysis of Dietary Intake,
      Restrained Eating and Opinions about Clean Eating among Women.
AB  - Clean eating is understood in broad terms to be an approach to eating which
      promotes the exclusion of processed foods. Social media and websites which
      promote clean eating are becoming increasingly popular as sources of nutrition
      information. Currently, there is a lack of knowledge regarding women's opinions
      about clean eating sites and their influence on eating behaviour. The aim of the
      present study was to investigate differences in dietary intake, dietary restraint
      and opinions about clean eating between women who had, and women who had never
      adhered to dietary advice from clean eating sites. Using a cross-sectional survey
      design, women (n = 762) ranging in age from 17-55 completed a self-report
      questionnaire on eating behaviour and beliefs about clean eating. Findings showed
      that 25.5% of the sample adhered to dietary advice from a clean eating site
      sometimes, often or very often. A significantly higher proportion of women who
      had adhered to dietary advice from clean eating sites met dietary guidelines for
      the consumption of fruit, meats and alternatives compared to women who had seldom
      or never adhered. Adherers also had significantly higher levels of restrained
      eating and were more positive about clean eating in general in comparison to
      those who seldom or never adhered. Results provide new information about exposure
      to clean eating sites and how they may influence women's eating practices. These
      preliminary findings suggest additional studies are required to better understand
      the influence of clean eating sites, particularly with regard to whether the
      information on such sites are from reputable sources and to what degree their
      recommendations may be problematic for individuals with eating concerns.

PMID- 30205541
TI  - Lipopolysaccharide Structural Differences between Western and Asian Helicobacter
      pylori Strains.
AB  - Recent structural analysis of the lipopolysaccharide (LPS) isolated from
      Helicobacter pylori G27 wild-type and O-antigen ligase mutant resulted in the
      redefinition of the core-oligosaccharide and O-antigen domains. The short core
      oligosaccharide (Glc-Gal-Hep-III-Hep-II-Hep-I-KDO) and its attached trisaccharide
      (Trio, GlcNAc-Fuc-Hep) appear to be highly conserved structures among H. pylori
      strains. The G27 LPS contains a linear glucan-heptan linker between the core-Trio
      and distal Lewis antigens. This linker domain was commonly identified in Western
      strains. In contrast, out of 12 partial LPS structures of Asian strains, none
      displayed the heptan moiety, despite the presence of Lewis antigens. This raises
      the question of how Lewis antigens are attached to the Trio, and whether the LPS
      structure of Asian strains contain another linker. Of note, a riban was
      identified as a linker in LPS of the mouse-adapted SS1 strain, suggesting that
      alternative linker structures can occur. In summary, additional full structural
      analyses of LPS in Asian strains are required to assess the presence or absence
      of an alternative linker in these strains. It will also be interesting to study
      the glucan-heptan linker moieties in pathogenesis as H. pylori infections in Asia
      are usually more symptomatic than the ones presented in the Western world.

PMID- 30205542
TI  - Electronic Effect on the Molecular Motion of Aromatic Amides: Combined Studies
      Using VT-NMR and Quantum Calculations.
AB  - Rotational barrier energy studies to date have focused on the amide bond of
      aromatic compounds from a kinetic perspective using quantum calculations and
      nuclear magnetic resonance (NMR). These studies provide valuable information, not
      only regarding the basic conformational properties of amide bonds but also the
      molecular gear system, which has recently gained interest. Thus, we investigate
      the precise motion of the amide bonds of two aromatic compounds using an
      experimental rotational barrier energy estimation by NMR experiments and a
      theoretical evaluation of the density functional theory calculation. The
      theoretical potential energy surface scan method combined with the quadratic
      synchronous transit 3 method and consideration of additional functional group
      rotation with optimization and frequency calculations support the results of the
      variable temperature 1H NMR, with deviations of less than 1 kcal/mol. This
      detailed experimental and theoretical research strongly supports molecular gear
      motion in the aromatic amide system, and the difference in kinetic energy
      indicates that the electronic effect from the aromatic structure has a key role
      in conformational movements at different temperatures. Our study provides an
      enhanced basis for future amide structural dynamics research.

PMID- 30205544
TI  - Removal of Microcystin-LR by a Novel Native Effective Bacterial Community
      Designated as YFMCD4 Isolated from Lake Taihu.
AB  - Microcystin-LR (MC-LR) is the most toxic and frequently detected monocyclic
      heptapeptide hepatotoxin produced by cyanobacteria, which poses a great threat to
      the natural ecosystem and public health. It is very important to seek environment
      friendly and cost-efficient methods to remove MC-LR in water. In this study, the
      MC-degrading capacities of a novel indigenous bacterial community designated as
      YFMCD4 and the influence of environmental factors including various temperatures,
      MC concentrations and pH on the MC-degrading activities were investigated
      utilizing high-performance liquid chromatography (HPLC). In addition, the MC
      degrading mechanism of YFMCD4 was also studied using HPLC coupled with a mass
      spectrometry equipped with electrospray ionization interface (HPLC-ESI-MS). The
      data showed MC-LR was completely removed at the maximum rate of 0.5 ug/(mL.h)
      under the optimal condition by YFMCD4. Two pure bacterial strains Alcaligenes
      faecalis and Stenotrophomonas acidaminiohila were isolated from YFMCD4 degraded
      MC-LR at a slower rate. The MC-degrading rates of YFMCD4 were significantly
      affected by different temperatures, pH and MC-LR concentrations. Two
      intermediates of a tetrapeptide and Adda appeared in the degradation process.
      These results illustrate that the novel YFMCD4 is one of the highest effective MC
      degrading bacterial community, which can completely remove MC-LR and possesses a
      significant potential to treat water bodies contaminated by MC-LR.

PMID- 30205543
TI  - The Gut-Brain Axis in Alzheimer's Disease and Omega-3. A Critical Overview of
      Clinical Trials.
AB  - Despite intensive study, neurodegenerative diseases remain insufficiently
      understood, precluding rational design of therapeutic interventions that can
      reverse or even arrest the progressive loss of neurological function. In the last
      decade, several theories investigating the causes of neurodegenerative diseases
      have been formulated and a condition or risk factor that can contribute is
      described by the gut-brain axis hypothesis: stress, unbalanced diet, and drugs
      impact altering microbiota composition which contributes to dysbiosis. An altered
      gut microbiota may lead to a dysbiotic condition and to a subsequent increase in
      intestinal permeability, causing the so-called leaky-gut syndrome. Herein, in
      this review we report recent findings in clinical trials on the risk factor of
      the gut-brain axis in Alzheimer's disease and on the effect of omega-3
      supplementation, in shifting gut microbiota balance towards an eubiosis status.
      Despite this promising effect, evidences reported in selected randomized clinical
      trials on the effect of omega-3 fatty acid on cognitive decline in Alzheimer's
      disease are few. Only Mild Cognitive Impairment, a prodromal state that could
      precede the progress to Alzheimer's disease could be affected by omega-3 FA
      supplementation. We report some of the critical issues which emerged from these
      studies. Randomized controlled trials in well-selected AD patients considering
      the critical points underlined in this review are warranted.

PMID- 30205546
TI  - Label-Free Rapid Separation and Enrichment of Bone Marrow-Derived Mesenchymal
      Stem Cells from a Heterogeneous Cell Mixture Using a Dielectrophoresis Device.
AB  - Bone marrow-derived mesenchymal stem cells (BMSCs) are an important cell resource
      for stem cell-based therapy, which are generally isolated and enriched by the
      density-gradient method based on cell size and density after collection of tissue
      samples. Since this method has limitations with regards to purity and
      repeatability, development of alternative label-free methods for BMSC separation
      is desired. In the present study, rapid label-free separation and enrichment of
      BMSCs from a heterogeneous cell mixture with bone marrow-derived promyelocytes
      was successfully achieved using a dielectrophoresis (DEP) device comprising saw
      shaped electrodes. Upon application of an electric field, HL-60 cells as models
      of promyelocytes aggregated and floated between the saw-shaped electrodes, while
      UE7T-13 cells as models of BMSCs were effectively captured on the tips of the saw
      shaped electrodes. After washing out the HL-60 cells from the device selectively,
      the purity of the UE7T-13 cells was increased from 33% to 83.5% within 5 min.
      Although further experiments and optimization are required, these results show
      the potential of the DEP device as a label-free rapid cell isolation system
      yielding high purity for rare and precious cells such as BMSCs.

PMID- 30205545
TI  - Examples of Weak, If Not Absent, Form-Function Relations in the Vertebrate Heart.
AB  - That form and function are related is a maxim of anatomy and physiology. Yet,
      form-function relations can be difficult to prove. Human subjects with excessive
      trabeculated myocardium in the left ventricle, for example, are diagnosed with
      non-compaction cardiomyopathy, but the extent of trabeculations may be without
      relation to ejection fraction. Rather than rejecting a relation between form and
      function, we may ask whether the salient function is assessed. Is there a
      relation to electrical propagation, mean arterial blood pressure, or propensity
      to form blood clots? In addition, how should the extent of trabeculated muscle be
      assessed? While reviewing literature on trabeculated muscle, we applied
      Tinbergen's four types of causation-how does it work, why does it work, how is it
      made, and why did it evolve-to better parse what is meant by form and function.
      The paper is structured around cases that highlight advantages and pitfalls of
      applying Tinbergen's questions. It further uses the evolution of lunglessness in
      amphibians to argue that lung reduction impacts on chamber septation and it
      considers the evolution of an arterial outflow in fishes to argue that reductions
      in energy consumption may drive structural changes with little consequences to
      function. Concerning trabeculations, we argue they relate to pumping function in
      the embryo in the few weeks before the onset of coronary circulation. In human
      fetal and postnatal stages, a spectrum of trabeculated-to-compact myocardium
      makes no difference to cardiac function and in this period, form and function may
      appear unrelated.

PMID- 30205547
TI  - Ag@SiO2 Core-shell Nanoparticles Embedded in a TiO2 Mesoporous Layer
      Substantially Improve the Performance of Perovskite Solar Cells.
AB  - In this study, Ag@SiO2 nanoparticles were synthesized by a modified Stober method
      for preparing the TiO2 mesoporous layer of carbon counter electrode-based
      perovskite solar cells (PSCs) without a hole transporting layer. Compared with
      normal PSCs (without Ag@SiO2 incorporated in the TiO2 mesoporous layer), PSCs
      with an optimal content of Ag@SiO2 (0.3 wt. % Ag@SiO2-TiO2) show a 19.46%
      increase in their power conversion efficiency, from 12.23% to 14.61%, which is
      mainly attributed to the 13.89% enhancement of the short-circuit current density,
      from 20.23 mA/cm2 to 23.04 mA/cm2. These enhancements mainly contributed to the
      localized surface Plasmon resonance effect and the strong scattering effect of
      Ag@SiO2 nanoparticles. However, increasing the Ag@SiO2 concentration in the
      mesoporous layer past the optimum level cannot further increase the short-circuit
      current density and incident photon-to-electron conversion efficiency of the
      devices, which is primarily ascribed to the electron transport pathways being
      impeded by the insulating silica shells inside the TiO2 network.

PMID- 30205548
TI  - Impact of Front-of-Pack Nutrition Labels on Portion Size Selection: An
      Experimental Study in a French Cohort.
AB  - In the European Union (EU) three coloured graded Front-of-Pack labels (FoPLs),
      two endorsed by governments (Nutri-Score and Multiple Traffic Lights (MTL)) and
      one designed by industry (Evolved Nutrition Label (ENL)) are currently being
      discussed. This study aimed to investigate the impact of these FoPLs on portion
      size selection, specifically for less healthy products. In 2018, participants
      from the French NutriNet-Sante cohort study (N = 25,772) were exposed through a
      web-based self-administered questionnaire to products from three food categories
      (sweet biscuits, cheeses, and sweet spreads), with or without FoPLs, and were
      invited to select the portion they would consume (in size and number). Kruskall
      Wallis tests, and mixed ordinal logistic regression models, were used to
      investigate the effects of FoPLs on portion size selection. Compared to no label,
      Nutri-Score consistently lowered portion sizes (OR = 0.76 (0.74-0.76)), followed
      by MTL (OR = 0.83 (0.82-0.84)). For ENL, the effects differed depending on the
      food group: It lowered portion size selection for cheeses (OR = 0.84 (0.83
      0.87)), and increased it for spreads (OR = 1.19 (1.15-1.22)). Nutri-Score
      followed by MTL appear efficient tools to encourage consumers to decrease their
      portion size for less healthy products, while ENL appears to have inconsistent
      effects depending on the food category.

PMID- 30205550
TI  - Sensor Selection to Improve Estimates of Particulate Matter Concentration from a
      Low-Cost Network.
AB  - Deployment of low-cost sensors in the field is increasingly popular. However,
      each sensor requires on-site calibration to increase the accuracy of the
      measurements. We established a laboratory method, the Average Slope Method, to
      select sensors with similar response so that a single, on-site calibration for
      one sensor can be used for all other sensors. The laboratory method was performed
      with aerosolized salt. Based on linear regression, we calculated slopes for 100
      particulate matter (PM) sensors, and 50% of the PM sensors fell within +/-14% of
      the average slope. We then compared our Average Slope Method with an Individual
      Slope Method and concluded that our first method balanced convenience and
      precision for our application. Laboratory selection was tested in the field,
      where we deployed 40 PM sensors inside a heavy-manufacturing site at spatially
      optimal locations and performed a field calibration to calculate a slope for
      three PM sensors with a reference instrument at one location. The average slope
      was applied to all PM sensors for mass concentration calculations. The calculated
      percent differences in the field were similar to the laboratory results.
      Therefore, we established a method that reduces the time and cost associated with
      calibration of low-cost sensors in the field.

PMID- 30205549
TI  - Causes of Morbidity and Mortality among Neonates and Children in Post-Conflict
      Burundi: A Cross-Sectional Retrospective Study.
AB  - The risk of a child dying before age five in Burundi is almost 1.6 times higher
      than that in the World Health Organization (WHO) African region. However,
      variations in the all-cause mortality rates across Burundi have not yet been
      measured directly at subnational levels, age group and by gender. The objective
      of this study was to describe the main causes of hospitalization and mortality in
      children during the neonatal period and at ages 1 to 59 months, for boys and
      girls, and to assess the total annual (2010) burden of under-five morbidity and
      mortality in hospitals using hospitalization records from 21 district hospitals.
      We found variation in the gender and regional distribution of the five leading
      causes of hospitalization and death of children under five. Although the five
      causes accounted for 89% (468/523) of all neonatal hospitalizations, three causes
      accounted for 93% (10,851/11,632) of all-cause hospitalizations for children ages
      1 to 59 months (malaria, lung disease, and acute diarrhea), malaria accounted for
      69% (1086/1566) of all deaths at ages 1 to 59 months. In Burundi, human malarial
      infections continue to be the main cause of hospitalization and mortality among
      under-five children.

PMID- 30205551
TI  - Evaluation of a Novel Classification of Heat-Related Illnesses: A Multicentre
      Observational Study (Heat Stroke STUDY 2012).
AB  - The Japanese Association for Acute Medicine Committee recently proposed a novel
      classification system for the severity of heat-related illnesses. The illnesses
      are simply classified into three stages based on symptoms and management or
      treatment. Stages I, II, and III broadly correspond to heat cramp and syncope,
      heat exhaustion, and heat stroke, respectively. Our objective was to examine
      whether this novel severity classification is useful in the diagnosis by
      healthcare professionals of patients with severe heat-related illness and organ
      failure. A nationwide surveillance study of heat-related illnesses was conducted
      between 1 June and 30 September 2012, at emergency departments in Japan. Among
      the 2130 patients who attended 102 emergency departments, the severity of their
      heat-related illness was recorded for 1799 patients, who were included in this
      study. In the patients with heat cramp and syncope or heat exhaustion (but not
      heat stroke), the blood test data (alanine aminotransferase, creatinine, blood
      urea nitrogen, and platelet counts) for those classified as Stage III were
      significantly higher than those of patients classified as Stage I or II. There
      were no deaths among the patients classified as Stage I. This novel
      classification may avoid underestimating the severity of heat-related illness.

PMID- 30205553
TI  - Association between Anaemia in Children 6 to 23 Months Old and Child, Mother,
      Household and Feeding Indicators.
AB  - In Low and Lower-Middle-Income countries, the prevalence of anaemia in infancy
      remains high. In early childhood anaemia cause irreversible cognitive deficits
      and represents a higher risk of child mortality. The consequences of anaemia in
      infancy are a major barrier to overcome poverty traps. The aim of this study was
      to analyse, based on a multi-level approach, different factors associated with
      anaemia in children 6-23 months old based on recent available Standard
      Demographic Health Surveys (S-DHS). We identified 52 S-DHS that had complete
      information in all covariates of interest in our analysis between 2005 and 2015.
      We performed traditional logistic regressions and multilevel logistic regression
      analyses to study the association between haemoglobin concentrations and
      household, child, maternal, socio-demographic variables. In our sample, 70% of
      the 6-23 months-old children were anaemic. Child anaemia was strongly associated
      with maternal anaemia, household wealth, maternal education and low birth weight.
      Children fed with fortified foods, potatoes and other tubers had significantly
      lower rates of anaemia. Improving overall household living conditions, increasing
      maternal education, delaying childbearing and introducing iron rich foods at six
      months of age may reduce the likelihood of anaemia in toddlerhood.

PMID- 30205555
TI  - Scattering Theory of Graphene Grain Boundaries.
AB  - The implementation of graphene-based electronics requires fabrication processes
      that are able to cover large device areas, since the exfoliation method is not
      compatible with industrial applications. The chemical vapor deposition of large
      area graphene represents a suitable solution; however, it has an important
      drawback of producing polycrystalline graphene with the formation of grain
      boundaries, which are responsible for the limitation of the device's performance.
      With these motivations, we formulate a theoretical model of a single-layer
      graphene grain boundary by generalizing the graphene Dirac Hamiltonian model. The
      model only includes the long-wavelength regime of the charge carrier transport,
      which provides the main contribution to the device conductance. Using symmetry
      based arguments deduced from the current conservation law, we derive
      unconventional boundary conditions characterizing the grain boundary physics and
      analyze their implications on the transport properties of the system. Angle
      resolved quantities, such as the transmission probability, are studied within the
      scattering matrix approach. The conditions for the existence of preferential
      transmission directions are studied in relation with the grain boundary
      properties. The proposed theory provides a phenomenological model to study grain
      boundary physics within the scattering approach, and represents per se an
      important enrichment of the scattering theory of polycrystalline graphene.
      Moreover, the outcomes of the theory can contribute to understanding and limiting
      the detrimental effects of graphene grain boundaries, while also providing a
      benchmark for more elaborate techniques.

PMID- 30205554
TI  - Integrative Histologic and Bioinformatics Analysis of BIRC5/Survivin Expression
      in Oral Squamous Cell Carcinoma.
AB  - Survivin is a well-known protein involved in the inhibition of apoptosis in many
      different cancer types. The aim of this study was to perform an integrated
      bioinformatic and histologic analysis in order to study the expression and
      prognostic role of Survivin and its related gene BIRC5 in oral cancer. Publicly
      available databases were accessed via Gene Expression Omnibus and Oncomine, in
      addition raw data from The Cancer Genome Atlas (TCGA) were also obtained in order
      to analyze the rate of gene mutation, expression and methylation in patients with
      oral squamous cells carcinoma (OSCC). Immunohistochemistry (IHC) was also
      performed in order to evaluate the nuclear and cytoplasmic expression of Survivin
      and their correlation with cell proliferation in samples from OSCC patients.
      Results of this study revealed that Survivin is rarely mutated in OSCC samples
      and upregulated when compared to non-cancerous tissue. A negative correlation
      between the methylation of the island cg25986496 and BIRC5 mRNA expression was
      detected from TCGA data. IHC staining revealed that cytoplasmic (and not nuclear)
      expression of Survivin is associated with poor overall survival in OSCC patients,
      while the nuclear expression correlates with higher proliferation rate. In
      addition, data from TCGA database revealed that BIRC5 gene expression is an
      independent prognostic factor for OSCC patients.

PMID- 30205552
TI  - Vitamin D: Effect on Haematopoiesis and Immune System and Clinical Applications.
AB  - Vitamin D is a steroid-like hormone which acts by binding to vitamin D receptor
      (VDR). It plays a main role in the calcium homeostasis and metabolism. In
      addition, vitamin D display other important effects called "non-classical
      actions." Among them, vitamin D regulates immune cells function and hematopoietic
      cells differentiation and proliferation. Based on these effects, it is currently
      being evaluated for the treatment of hematologic malignancies. In addition,
      vitamin D levels have been correlated with patients' outcome after allogeneic
      stem cell transplantation, where it might regulate immune response and,
      accordingly, might influence the risk of graft-versus-host disease. Here, we
      present recent advances regarding its clinical applications both in the treatment
      of hematologic malignancies and in the transplant setting.

PMID- 30205556
TI  - Effect of Vapor Pressure During the Steam Coating Treatment on Structure and
      Corrosion Resistance of the Mg(OH)2/Mg-Al LDH Composite Film Formed on Mg Alloy
      AZ61.
AB  - Corrosion resistant films with almost the same film thickness were prepared on
      the magnesium alloy AZ61 by steam coating at different vapor pressure and
      treatment times. The effect of the vapor pressure on the structures and the
      corrosion resistance of the films was investigated by using FE-SEM, SEM-EDX,
      GAXRD, and potentiodynamic polarization curve measurements in a 3.5 mass
      percentage NaCl aqueous solution. These studies clarified that the interlayers of
      Mg-Al Layered Double Hydroxide (LDHs) increased and its structure became non
      uniform with an increase in the vapor pressure. The corrosion current density
      slightly increased with an increase in the vapor pressure during the treatment,
      but pitting corrosion occurred at both low and high vapor pressures. These
      results indicate that water molecules were pushed into an interlayer of Mg-Al
      LDHs by high vapor pressure. Consequently, the interlayer distance of Mg-Al LDH
      was widened and the cracks were generated in the anti-corrosive film. On the
      other hand, the Mg-Al LDH with an insufficiently large interlayer distance could
      not fill the cracks in the Mg(OH)2 crystallites and caused pitting corrosion when
      the vapor pressure was low.

PMID- 30205558
TI  - Tetranuclear Oxo-Titanium Clusters with Different Carboxylate Aromatic Ligands:
      Optical Properties, DFT Calculations, and Photoactivity.
AB  - Titanium(IV) oxo-clusters of the general formula (Ti4O2(OiBu)10(O2CR')2) (R' =
      C13H9 (1), PhCl (2), PhNO2 (3)) were studied in order to estimate their potential
      photoactivity. The structure of the resulting tetranuclear Ti(IV) oxo-complexes
      was then determined via single crystal X-ray diffraction, infrared and Raman
      spectroscopy, and electron spin resonance (ESR). An analysis of diffuse
      reflectance spectra (DRS) allowed for the assessment of band gap values of (1)
      (3) microcrystalline samples complexes. The use of different carboxylate ligands
      allowed the band gap of tetranuclear Ti(IV) oxo-clusters to be modulated in the
      range of 3.6 eV-2.5 eV. Density functional theory (DFT) methods were used to
      explain the influence of substitutes on band gap and optical activity. Dispersion
      of (1)-(3) microcrystals in the poly(methyl methacrylate) (PMMA) matrixes enabled
      the formation of composite materials for which the potential photocatalytic
      activity was estimated through the study on methylene blue (MB) photodegradation
      processes in the presence of UV light. The results obtained revealed a
      significant influence of carboxylate ligands functionalization on the
      photoactivity of synthesized tetranuclear Ti(IV) oxo-complexes.

PMID- 30205557
TI  - Selenium-Related Transcriptional Regulation of Gene Expression.
AB  - The selenium content of the body is known to control the expression levels of
      numerous genes, both so-called selenoproteins and non-selenoproteins. Selenium is
      a trace element essential to human health, and its deficiency is related to, for
      instance, cardiovascular and myodegenerative diseases, infertility and
      osteochondropathy called Kashin-Beck disease. It is incorporated as
      selenocysteine to the selenoproteins, which protect against reactive oxygen and
      nitrogen species. They also participate in the activation of the thyroid hormone,
      and play a role in immune system functioning. The synthesis and incorporation of
      selenocysteine occurs via a special mechanism, which differs from the one used
      for standard amino acids. The codon for selenocysteine is a regular in-frame stop
      codon, which can be passed by a specific complex machinery participating in
      translation elongation and termination. This includes a presence of
      selenocysteine insertion sequence (SECIS) in the 3'-untranslated part of the
      selenoprotein mRNAs. Nonsense-mediated decay is involved in the regulation of the
      selenoprotein mRNA levels, but other mechanisms are also possible. Recent
      transcriptional analyses of messenger RNAs, microRNAs and long non-coding RNAs
      combined with proteomic data of samples from Keshan and Kashin-Beck disease
      patients have identified new possible cellular pathways related to
      transcriptional regulation by selenium.

PMID- 30205561
TI  - Prevention of Cervical Cancer in Sub-Saharan Africa: The Advantages and
      Challenges of HPV Vaccination.
AB  - Cervical cancer is a critical public health issue in sub-Saharan Africa (SSA),
      where it is the second leading cause of cancer among women and the leading cause
      of female cancer deaths. Incidence and mortality rates are substantially higher
      than in high-income countries with population-based screening programs, yet
      implementing screening programs in SSA has so far proven to be challenging due to
      financial, logistical, and sociocultural factors. Human Papillomavirus (HPV)
      vaccination is an effective approach for primary prevention of cervical cancer
      and presents an opportunity to reduce the burden from cervical cancer in SSA.
      With a number of SSA countries now eligible for Global Alliance for Vaccines and
      Immunization (GAVI) support for vaccine introduction, it is timely to consider
      the factors that impede and facilitate implementation of vaccine programs in SSA.
      This article describes epidemiological features of cervical cancer in SSA and the
      current status of HPV vaccine implementation in SSA countries. Rwanda's
      experience of achieving high vaccination coverage in their national HPV
      immunization program is used as a case study to explore effective approaches to
      the design and implementation of HPV vaccination programs in SSA. Key factors in
      Rwanda's successful implementation included government ownership and support for
      the program, school-based delivery, social mobilization, and strategies for
      reaching out-of-school girls. These findings might usefully be applied to other
      SSA countries planning for HPV vaccination.

PMID- 30205560
TI  - Identification of Novel Quantitative Trait Loci Linked to Crown Rot Resistance in
      Spring Wheat.
AB  - Crown rot (CR), caused by various Fusarium species, is a major disease in many
      cereal-growing regions worldwide. Fusarium culmorum is one of the most important
      species, which can cause significant yield losses in wheat. A set of 126 advanced
      International Maize and Wheat Improvement Center (CIMMYT) spring bread wheat
      lines were phenotyped against CR for field crown, greenhouse crown and stem, and
      growth room crown resistance scores. Of these, 107 lines were genotyped using
      Diversity Array Technology (DArT) markers to identify quantitative trait loci
      linked to CR resistance by genome-wide association study. Results of the
      population structure analysis grouped the accessions into three sub-groups.
      Genome wide linkage disequilibrium was large and declined on average within 20 cM
      (centi-Morgan) in the panel. General linear model (GLM), mixed linear model
      (MLM), and naive models were tested for each CR score and the best model was
      selected based on quarantine-quarantine plots. Three marker-trait associations
      (MTAs) were identified linked to CR resistance; two of these on chromosome 3B
      were associated with field crown scores, each explaining 11.4% of the phenotypic
      variation and the third MTA on chromosome 2D was associated with greenhouse stem
      score and explained 11.6% of the phenotypic variation. Together, these newly
      identified loci provide opportunity for wheat breeders to exploit in enhancing CR
      resistance via marker-assisted selection or deployment in genomic selection in
      wheat breeding programs.

PMID- 30205559
TI  - MC1R: Front and Center in the Bright Side of Dark Eumelanin and DNA Repair.
AB  - Melanin, the pigment produced by specialized cells, melanocytes, is responsible
      for skin and hair color. Skin pigmentation is an important protective mechanism
      against the DNA damaging and mutagenic effects of solar ultraviolet radiation
      (UV). It is acknowledged that exposure to UV is the main etiological
      environmental factor for all forms of skin cancer, including melanoma. DNA repair
      capacity is another major factor that determines the risk for skin cancer. Human
      melanocytes synthesize eumelanin, the dark brown form of melanin, as well as
      pheomelanin, which is reddish-yellow in color. The relative rates of eumelanin
      and pheomelanin synthesis by melanocytes determine skin color and the sensitivity
      of skin to the drastic effects of solar UV. Understanding the complex regulation
      of melanocyte function and how it responds to solar UV has a huge impact on
      developing novel photoprotective strategies to prevent skin cancer, particularly
      melanoma, the most fatal form, which originates from melanocytes. This review
      provides an overview of the known differences in the photoprotective effects of
      eumelanin versus pheomelanin, how these two forms of melanin are regulated
      genetically and biochemically, and their impact on the DNA damaging effects of UV
      exposure. Additionally, this review briefly discusses the role of paracrine
      factors, focusing on alpha-melanocortin (alpha-melanocyte stimulating hormone;
      alpha-MSH), in regulating melanogenesis and the response of melanocytes to UV,
      and describes a chemoprevention strategy based on targeting the melanocortin 1
      receptor (MC1R) by analogs of its physiological agonist alpha-MSH.

PMID- 30205564
TI  - Strong Coupling of Folded Phonons with Plasmons in 6H-SiC Micro/Nanocrystals.
AB  - Silicon carbide (SiC) has a large number of polytypes of which 3C-, 4H-, 6H-SiC
      are most common. Since different polytypes have different energy gaps and
      electrical properties, it is important to identify and characterize various SiC
      polytypes. Here, Raman scattering is performed on 6H-SiC micro/nanocrystal (MNC)
      films to investigate all four folded transverse optic (TO) and longitudinal optic
      (LO) modes. With increasing film thickness, the four folded TO modes exhibit the
      same frequency downshift, whereas the four folded LO modes show a gradually
      reduced downshift. For the same film thickness, all the folded modes show larger
      frequency downshifts with decreasing MNC size. Based on plasmons on MNCs, these
      folded modes can be attributed to strong coupling of the folded phonons with
      plasmons which show different strengths for the different folded modes while
      changing the film thickness and MNC size. This work provides a useful technique
      to identify SiC polytypes from Raman scattering.

PMID- 30205562
TI  - Bark of Passiflora edulis Treatment Stimulates Antioxidant Capacity, and Reduces
      Dyslipidemia and Body Fat in db/db Mice.
AB  - Obesity is considered an important risk factor for several disorders, such as
      diabetes mellitus, systemic arterial hypertension, dyslipidemia, and
      atherosclerosis, which are associated with inflammation and oxidative stress as a
      trigger factor. Passiflora edulis contains important bioactive compounds, such as
      phenolics, carotenoids, vitamin C, and polyamines in pulp, leaves, seeds, and
      bark. Aim: To evaluate the effect of bark of Passiflora edulis (BPe) on body
      composition, and metabolic and oxidative stress parameters in genetically obese
      mice. Methods: Obese male db/db mice (n = 14 animals) received normal feeds and
      water ad libitum for 8 weeks. Then, animals were randomly divided to continue
      either receiving standard chow (obese, n = 7 (OB)) or feed with standard chow
      plus bark Passiflora edulis (BPe) (obese + BPe, n = 7 (OB + BPe)) for 8 more
      weeks, totaling 16 weeks. BPe was added to chow (7 g of BPe/kg of chow
      corresponding to 1.5 g/kg of body weight). The parameters evaluated in animals
      included food and caloric intake, body weight, body fat, plasma glucose,
      triglycerides, and total cholesterol. Malondialdehyde and antioxidant capacity
      were evaluated in plasma and organs. Groups were compared by Student t-test, with
      p < 0.05. Results: BPe reduced visceral and subcutaneous fat deposit and
      adiposity index, cholesterol and triglyceride levels, ameliorated the antioxidant
      capacity, and reduced malondialdehyde (MDA) levels. Conclusion: the bark of
      Passiflora edulis was effective in improving body composition, and metabolic and
      antioxidant parameters in obese mice.

PMID- 30205565
TI  - A Simple and Low-Cost Optical Fiber Intensity-Based Configuration for
      Perfluorinated Compounds in Water Solution.
AB  - We present a very simple approach for the detection of the Perfluorinated
      Alkylated Substances (PFAs) in water solution. Perfluorooctanesulfonate (PFOS)
      and Perfluorooctanoate (PFOA) are the most extensively investigated
      perfluoroalkyl and polyfluoroalkyl substances in water because human exposition
      can occur through different pathways, even if the dietary intake seems to be
      their main route of exposure. The developed sensor is based on a specific
      Molecularly Imprinted Polymer (MIP) receptor deposited on a simple D-shaped
      Plastic Optical Fiber (POF) platform. This novel chemical sensor has been
      characterized using a very simple and low-cost experimental setup based on an LED
      and two photodetectors. This optical sensor system is an alternative method to
      monitor the presence of contaminants with an MIP receptor, instead of a surface
      plasmon resonance (SPR) sensor in D-shaped POFs. For the sake of comparison, the
      results obtained exploiting the same MIP for PFAs on a classic SPR-POF sensor
      have been reported. The experimental results have shown that the actual limit of
      detection of this new configuration was about 0.5 ppb. It is similar to the one
      obtained by the configuration based on an SPR-POF with the same MIP receptor.

PMID- 30205566
TI  - Molecular Characterisation and Functions of Fis1 and PDCD6 Genes from
      Echinococcus granulosus.
AB  - Cystic echinococcosis, a parasitic zoonosis that causes significant economic
      losses and poses a threat to public health, is caused by larvae of the tapeworm
      Echinococcus granulosus. Infection causes infertile cysts in intermediate hosts
      that cannot produce protoscoleces (PSCs) or complete the life cycle. Herein, we
      cloned, expressed, and characterised mitochondrial fission protein 1 (Eg-Fis1)
      and programmed cell death protein 6 (Eg-PDCD6) from E. granulosus, and explored
      their functions related to infertile cysts. Eg-Fis1 and Eg-PDCD6 encode putative
      157 and 174 residue proteins, respectively, and Western blotting indicated good
      reactogenicity for both. Eg-Fis1 and Eg-PDCD6 were ubiquitously distributed in
      all stages of E. granulosus. Furthermore, mRNAs of Eg-Fis1 and Eg-PDCD6 were
      upregulated following H2O2 treatment which induced apoptosis in PSCs. To
      investigate the regulation of apoptosis in response to oxidative stress, RNA
      interference (RNAi) and terminal deoxynucleotidyl transferase dUTP nick-end
      labelling (TUNEL) assays were performed. The apoptotic rate of the Eg-Fis1 RNAi
      group was significantly lower than non-interference group, but there was no such
      difference for Eg-PDCD6. In conclusion, Eg-Fis1 promotes apoptosis induced by
      oxidative stress, whereas Eg-PDCD6 does not appear to be a key regulator of
      apoptosis.

PMID- 30205568
TI  - New Approaches to the Integration of Navigation Systems for Autonomous Unmanned
      Vehicles (UAV).
AB  - The article presents an overview of the theoretical and experimental work related
      to unmanned aerial vehicles (UAVs) motion parameters estimation based on the
      integration of video measurements obtained by the on-board optoelectronic camera
      and data from the UAV's own inertial navigation system (INS). The use of various
      approaches described in the literature which show good characteristics in
      computer simulations or in fairly simple conditions close to laboratory ones
      demonstrates the sufficient complexity of the problems associated with adaption
      of camera parameters to the changing conditions of a real flight. In our
      experiments, we used computer simulation methods applying them to the real images
      and processing methods of videos obtained during real flights. For example, it
      was noted that the use of images that are very different in scale and in the
      aspect angle from the observed images in flight makes it very difficult to use
      the methodology of singular points. At the same time, the matching of the
      observed and reference images using rectilinear segments, such as images of road
      sections and the walls of the buildings look quite promising. In addition, in our
      experiments we used the projective transformation matrix computation from frame
      to frame, which together with the filtering estimates for the coordinate and
      angular velocities provides additional possibilities for estimating the UAV
      position. Data on the UAV position determining based on the methods of video
      navigation obtained during real flights are presented. New approaches to video
      navigation obtained using the methods of conjugation rectilinear segments,
      characteristic curvilinear elements and segmentation of textured and colored
      regions are demonstrated. Also the application of the method of calculating
      projective transformations from frame-to-frame is shown which gives estimates of
      the displacements and rotations of the apparatus and thereby serves to the UAV
      position estimation by filtering. Thus, the aim of the work was to analyze
      various approaches to UAV navigation using video data as an additional source of
      information about the position and velocity of the vehicle.

PMID- 30205567
TI  - Additive-Free Rice Starch-Assisted Synthesis of Spherical Nanostructured Hematite
      for Degradation of Dye Contaminant.
AB  - Nanostructured hematite materials for advanced applications are conventionally
      prepared with the presence of additives, tainting its purity with remnants of
      copolymer surfactants, active chelating molecules, stabilizing agents, or co
      precipitating salts. Thus, preparing nanostructured hematite via additive-free
      and green synthesis methods remains a huge hurdle. This study presents an
      environmentally friendly and facile synthesis of spherical nanostructured
      hematite (Sp-HNP) using rice starch-assisted synthesis. The physicochemical
      properties of the Sp-HNP were investigated by Fourier-transform infrared
      spectroscopy (FTIR), X-ray diffraction (XRD), thermogravimetric analysis (TGA),
      field emission scanning electron microscopy (FESEM), energy dispersive X-ray
      spectroscopy (EDX), transmission electron microscopy (TEM), UV-Vis diffuse
      reflectance spectroscopy (DR UV-Vis), and nitrogen adsorption-desorption
      analysis. The Sp-HNP showed a well-crystallized structure of pure rhombohedral
      phase, having a spherical-shaped morphology from 24 to 48 nm, and a surface area
      of 20.04 m2/g. Moreover, the Sp-HNP exhibited enhanced photocatalytic degradation
      of methylene blue dye, owing to the large surface-to-volume ratio. The current
      work has provided a sustainable synthesis route to produce spherical
      nanostructured hematite without the use of any hazardous agents or toxic
      additives, in agreement with the principles of green chemistry for the
      degradation of dye contaminant.

PMID- 30205569
TI  - Three New Iridoid Derivatives Have Been Isolated from the Stems of Neonauclea
      reticulata (Havil.) Merr. with Cytotoxic Activity on Hepatocellular Carcinoma
      Cells.
AB  - Three new iridoids, namely neonanin A (1), neonanin B (2) and neoretinin A (3),
      as well as twelve known compounds, 6-hydroxy-7-methyl-1-oxo-4
      carbomethoxyoctahydrocyclopenta[c]pyran (4), 4-epi-alyxialactone (5), loganetin
      (6), loganin (7), phenylcoumaran-alpha'-aldehyde (8), cleomiscosin A (9), ficusal
      (10), balanophonin (11), vanillic acid (12), p-coumaric acid (13), cis,trans
      abscisic acid (14), and trans,trans-abscisic acid (15) were isolated from the
      stems of Neonauclea reticulata (Havil.) Merr. These new structures were
      determined by the detailed analysis of spectroscopic data and comparison with the
      data of known analogues. Compounds 1-13 were evaluated using an in-vitro MTT
      cytotoxic assay for hepatocellular carcinoma (HCC) cells, and the preliminary
      results showed that ficusal (10), balanophonin (11), and p-coumaric acid (13)
      exhibited moderate cytotoxic activity, with EC50 values of 85.36 +/- 4.36, 92.63
      +/- 1.41, and 29.18 +/- 3.48 ug/mL against Hep3B cells, respectively.

PMID- 30205570
TI  - Molybdenum Trioxide: Efficient Nanosorbent for Removal of Methylene Blue Dye from
      Aqueous Solutions.
AB  - Nano Molybdenum trioxide (alpha-MoO3) was synthesized in an easy and efficient
      approach. The removal of methylene blue (MB) in aqueous solutions was studied
      using this material. The effects of various experimental parameters, for example
      contact time, pH, temperature and initial MB concentration on removal capacity
      were explored. The removal of MB was significantly affected by pH and temperature
      and higher values resulted in increase of removal capacity of MB. The removal
      efficiency of Methylene blue was 100% at pH = 11 for initial dye concentrations
      lower than 150 ppm, with a maximum removal capacity of 152 mg/g of MB as gathered
      from Langmuir model. By comparing the kinetic models (pseudo first-order, pseudo
      second-order and intraparticle diffusion model) at various conditions, it has
      been found that the pseudo second-order kinetic model correlates with the
      experimental data well. The thermodynamic study indicated that the removal was
      endothermic, spontaneous and favorable. The thermal regeneration studies
      indicated that the removal efficiency (99%) was maintained after four cycles of
      use. Fourier Transform Infrared (FTIR) and Scanning Electron Microscopy (SEM)
      confirmed the presence of the MB dye on the alpha-MoO3 nanoparticles after
      adsorption and regeneration. The alpha-MoO3 nanosorbent showed excellent removal
      efficiency before and after regeneration, suggesting that it can be used as a
      promising adsorbent for removing Methylene blue dye from wastewater.

PMID- 30205571
TI  - Characterization of Children's Exposure to Extremely Low Frequency Magnetic
      Fields by Stochastic Modeling.
AB  - In this study, children's exposure to extremely low frequency magnetic fields
      (ELF-MF, 40-800 Hz) is investigated. The interest in this thematic has grown due
      to a possible correlation between the increased risk of childhood leukemia and a
      daily average exposure above 0.4 uT, although the causal relationship is still
      uncertain. The aim of this paper was to present a new method of characterizing
      the children's exposure to ELF-MF starting from personal measurements using a
      stochastic approach based on segmentation (and to apply it to the personal
      measurements themselves) of two previous projects: the ARIMMORA project and the
      EXPERS project. The stochastic model consisted in (i) splitting the 24 h
      recordings into stationary events and (ii) characterizing each event with four
      parameters that are easily interpretable: the duration of the event, the mean
      value, the dispersion of the magnetic field over the event, and a final parameter
      characterizing the variation speed. Afterward, the data from the two databases
      were divided in subgroups based on a characteristic (i.e., children's age, number
      of inhabitants in the area, etc.). For every subgroup, the kernel density
      estimation (KDE) of each parameter was calculated and the p-value histogram of
      the parameters together was obtained, in order to compare the subgroups and to
      extract information about the children's exposure. In conclusion, this new
      stochastic approach allows for the identification of the parameters that most
      affect the level of children's exposure.

PMID- 30205563
TI  - Clinical and Biological Characterization of Skin Pigmentation Diversity and Its
      Consequences on UV Impact.
AB  - Skin color diversity is the most variable and noticeable phenotypic trait in
      humans resulting from constitutive pigmentation variability. This paper will
      review the characterization of skin pigmentation diversity with a focus on the
      most recent data on the genetic basis of skin pigmentation, and the various
      methodologies for skin color assessment. Then, melanocyte activity and amount,
      type and distribution of melanins, which are the main drivers for skin
      pigmentation, are described. Paracrine regulators of melanocyte microenvironment
      are also discussed. Skin response to sun exposure is also highly dependent on
      color diversity. Thus, sensitivity to solar wavelengths is examined in terms of
      acute effects such as sunburn/erythema or induced-pigmentation but also long-term
      consequences such as skin cancers, photoageing and pigmentary disorders. More
      pronounced sun-sensitivity in lighter or darker skin types depending on the
      detrimental effects and involved wavelengths is reviewed.

PMID- 30205573
TI  - Translation and Validation of the Korean Version of the Revised Health Care
      System Distrust Scale (HCSD-K) in Korean American Women.
AB  - BACKGROUND: Trust in the healthcare system is a major contributor for racial
      disparities in health and health care. We aimed to formally translate and cross
      culturally adapt the Korean version of the Revised Health Care System Distrust
      (HCSD-K) scale with a sample of Korean American women and examine the
      psychometric properties of the HCSD-K scale. METHODS: Ten Korean American women
      participated in the cognitive interview. A self-administered questionnaire was
      completed by 196 Korean American women aged 50-74 years. Instrument adaptation
      was performed using committee-based translation and cognitive interviewing.
      Construct validity, convergent validity, and internal consistency were examined
      to evaluate the psychometric properties of the HCSD-K scale. RESULTS: The
      translated instrument was found to be semantically sound. A confirmatory factor
      analysis revealed a two-factor structure with an excellent fit. Convergent
      validity was supported by correlations between the HCSD-K scale and both the
      Perceived Discrimination in Health Care and Trust in Physician scales. Cronbach's
      alpha for the total HCSD-K was 0.83. CONCLUSION: The nine-item HCSD-K scale
      demonstrated satisfactory reliability and validity. It is an appropriate
      instrument for measuring healthcare system distrust in Korean American women.
      Further study is needed to confirm the study results in a gender-mixed Korean
      population.

PMID- 30205572
TI  - A One-Step Extraction and Luminescence Assay for Quantifying Glucose and ATP
      Levels in Cultured HepG2 Cells.
AB  - A fluorescence-based enzymatic microplate intracellular glucose assay was
      designed and fully validated. The method was tested in a hepatocellular cancer
      cell line (HepG2). Our novel one-step extraction reagent gave stable cell lysates
      for glucose, adenosine triphosphate (ATP), and total protein determination from
      the same sample. Limit of detection for glucose was 0.13 uM (26 pmol/well), which
      is superior to commercially available glucose assays. Both intra- and interday
      assay imprecision in HepG2 cultures were less than 12% coefficient of variance
      (CV). In cell lysates spiked with glucose, recovery at two levels varied between
      83.70% and 91.81%, and both linearity and stability were acceptable. HepG2 cells
      treated with agents affecting glucose uptake/metabolism (phloretin, quercetin,
      quercetin-3'-sulfate, NaF, 3-bromopyruvate, NaN3, oligomycin A, ochratoxin A,
      cytochalasin B, and anti-GLUT1 antibody) showed dose-dependent changes in glucose
      and ATP levels without total protein (cell) loss. Finally, we performed flow
      cytometric glucose uptake measurement in the treated cells using 2-[N-(7
      nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxyglucose fluorescent glucose analog.
      Glucose uptake did not always mirror the intracellular glucose levels, which most
      likely reflects the differences between the two methodologies. However,
      interpreting data obtained by both methods and taking ATP/protein levels at the
      same time, one can get information on the mode of action of the compounds.

PMID- 30205574
TI  - Biocatalysis of Platycoside E and Platycodin D3 Using Fungal Extracellular beta
      Glucosidase Responsible for Rapid Platycodin D Production.
AB  - Platycodi radix (i.e., Platycodon grandiflorum root) products (e.g., tea,
      cosmetics, and herbal supplements) are popular in East Asian nutraceutical
      markets due to their reported health benefits and positive consumer perceptions.
      Platycosides are the key drivers of Platycodi radixes' biofunctional effects;
      their nutraceutical and pharmaceutical activities are primarily related to the
      number and varieties of sugar side-chains. Among the various platycosides,
      platycodin D is a major saponin that demonstrates various nutraceutical
      activities. Therefore, the development of a novel technology to increase the
      total platycodin D content in Platycodi radix extract is important, not only for
      consumers' health benefits but also producers' commercial applications and
      manufacturing cost reduction. It has been reported that hydrolysis of platycoside
      sugar moieties significantly modifies the compound's biofunctionality. Platycodi
      radix extract naturally contains two major platycodin D precursors (platycoside E
      and platycodin D3) which can be enzymatically converted to platycodin D via beta
      d-glucosidase hydrolysis. Despite evidence that platycodin D precursors can be
      changed to platycodin D in the Platycodi radix plant, there is little research on
      increasing platycodin D concentrations during processing. In this work,
      platycodin D levels in Platycodi radix extracts were significantly increased via
      extracellular Aspergillus usamii beta-d-glucosidase (n = 3, p < 0.001). To
      increase the extracellular beta-d-glucosidase activity, A. usamii was cultivated
      in a culture media containing cellobiose as its major carbon source. The optimal
      pH and temperature of the fungal beta-d-glucosidase were 6.0 and 40.0  degrees C,
      respectively. Extracellular A. usamii beta-d-glucosidase successfully converted
      more than 99.9% (w/v, n = 3, p < 0.001) of platycoside E and platycodin D3 into
      platycodin D within 2 h under optimal conditions. The maximum level of platycodin
      D was 0.4 mM. Following the biotransformation process, the platycodin D was
      recovered using preparatory High Performance Liquid Chromatography (HPLC) and
      applied to in vitro assays to evaluate its quality. Platycodin D separated from
      the Platycodi radix immediately following the bioconversion process showed
      significant anti-inflammatory effects from the Lipopolysaccharide (LPS)-induced
      macrophage inflammatory responses with decreased nitrite and IL-6 production (n =
      3, p < 0.001). Taken together, these results provide evidence that biocatalysis
      of Platycodi radix extracts with A. usamii may be used as an efficient method of
      platycodin D-enriched extract production and novel Platycodi radix products may
      thereby be created.

PMID- 30205576
TI  - Bearings Downsizing by Strength Enhancement and Service Life Extension.
AB  - Slim bearings are used widely in aircrafts, robots, wind turbines, and industrial
      machineries, where their size and weight are very important for the performance
      of a system. The common materials of slim bearings for robots and industrial
      machineries are based on SAE52110 bearing steel, and special heat treatment and a
      super polishing process are used and adapted to improve the rolling contact
      fatigue (RCF) strength of bearings. The improvement in RCF strength, depending on
      contact stress, surface hardness, and the friction behavior before and after
      ultrasonic nanocrystalline surface modification (UNSM) treatment was validated.
      Simple analysis shows that these improvements can reduce the size and weight of
      slim bearings down to about 3.40-21.25% and 14.3-26.05%, respectively. Hence,
      this UNSM technology is an opportunity to implement cost-saving and energy
      consuming super-polishing, a heat treatment process, and to reduce the size and
      weight of slim bearings.

PMID- 30205575
TI  - Physiology Based Approaches for Breeding of Next-Generation Food Legumes.
AB  - Plant breeders and agricultural scientists of the 21st century are challenged to
      increase the yield potentials of crops to feed the growing world population.
      Climate change, the resultant stresses and increasing nutrient deficiencies are
      factors that are to be considered in designing modern plant breeding pipelines.
      Underutilized food legumes have the potential to address these issues and ensure
      food security in developing nations of the world. Food legumes in the past have
      drawn limited research funding and technological attention when compared to
      cereal crops. Physiological breeding strategies that were proven to be successful
      in cereals are to be adapted to legume crop improvement to realize their
      potential. The gap between breeders and physiologists should be narrowed by
      collaborative approaches to understand complex traits in legumes. This review
      discusses the potential of physiology based approaches in food legume breeding
      and how they impact yield gains and abiotic stress tolerance in these crops. The
      influence of roots and root system architectures in food legumes' breeding is
      also discussed. Molecular breeding to map the relevant physiological traits and
      the potentials of gene editing those traits are detailed. It is imperative to
      unlock the potentials of these underutilized crops to attain sustainable
      environmental and nutritional food security.

PMID- 30205578
TI  - Have Studies that Measure Lumbar Kinematics and Muscle Activity Concurrently
      during Sagittal Bending Improved Understanding of Spinal Stability and Sub-System
      Interactions? A Systematic Review.
AB  - In order to improve understanding of the complex interactions between spinal sub
      systems (i.e., the passive (ligaments, discs, fascia and bones), the active
      (muscles and tendons) and the neural control systems), it is necessary to take a
      dynamic approach that incorporates the measurement of multiple systems
      concurrently. There are currently no reviews of studies that have investigated
      dynamic sagittal bending movements using a combination of electromyography (EMG)
      and lumbar kinematic measurements. As such it is not clear how understanding of
      spinal stability concepts has advanced with regards to this functional movement
      of the spine. The primary aim of this review was therefore to evaluate how such
      studies have contributed to improved understanding of lumbar spinal stability
      mechanisms. PubMed and Cochrane databases were searched using combinations of the
      keywords related to spinal stability and sagittal bending tasks, using strict
      inclusion and exclusion criteria and adhering to PRISMA guidelines. Whilst
      examples of the interactions between the passive and active sub-systems were
      shown, typically small sample sizes meant that results were not generalizable.
      The majority of studies used regional kinematic measurements, and whilst this was
      appropriate in terms of individual study aims, the studies could not provide
      insight into sub-system interaction at the level of the spinal motion segment. In
      addition, the heterogeneity in methodologies made comparison between studies
      difficult. The review suggests that since Panjabi's seminal spinal control
      papers, only limited advancement in the understanding of these theories has been
      provided by the studies under review, particularly at an inter-segmental level.
      This lack of progression indicates a requirement for new research approaches that
      incorporate multiple system measurements at a motion segment level.

PMID- 30205577
TI  - lncRNAs in Non-Malignant Tissue Have Prognostic Value in Colorectal Cancer.
AB  - Although colorectal cancer (CRC) is the third most frequent cause of cancer
      related death in Europe, clinically relevant biomarkers for therapy guidance and
      prognosis are insufficiently reliable. Long non-coding RNAs (lncRNAs) are RNAs
      over 200 nucleotides long that are not translated into proteins but can influence
      biological processes. There is emerging evidence for their involvement in solid
      cancer as oncogenes, tumour suppressors or regulators of cell proliferation and
      metastasis development. The goal of this study was to evaluate the prognostic
      effect of selected lncRNAs in a retrospective study on CRC patients from the
      Czech Republic. We used a quantitative PCR approach to measure the expression in
      paired non-malignant and tumour tissue samples of CRC patients of nine lncRNAs
      previously shown to be involved in cancer progression-ANRIL, CCAT1, GAS5, linc
      ROR, MALAT1, MIR155HG, PCAT1, SPRY4-IT1 and TUG1. Associations between expression
      and expression ratios and clinical characteristics and survival were assessed by
      using univariable Cox proportional hazards models, Kaplan-Meier estimations with
      the Gehan-Wilcoxon test, the Mann-Whitney U test, the Kruskal-Wallis test and
      Spearman's correlations. A comparison of expression in tumour tissue (TT) and non
      malignant mucosa tissue (MT) showed significant upregulation of CCAT1 and linc
      ROR in TT (p < 0.001 and p = 0.001, respectively) and downregulation of ANRIL,
      MIR155HG and MALAT1 (p = 0.001, p = 0.010, p = 0.001, respectively). Linc-ROR was
      significantly associated with the presence of synchronous metastases (p = 0.033).
      For individual tissue types, lower MIR155HG expression in TT was correlated with
      both shorter overall survival (p = 0.008) and shorter disease-free survival (p =
      0.040). In MT, expression ratios of CCAT1/ANRIL and CCAT1/MIR155HG were
      associated with overall survival (p = 0.005 and p = 0.006, respectively). Our
      results revealed that changes in expression of lncRNAs between MT and TT hold
      potential to be used as prognostic biomarkers in CRC patients. Moreover, the
      ratios of CCAT1 to ANRIL and MIR155HG in MT also exhibit potential for prognosis
      assessment without tumour sampling. Our results also indicate that cancer
      progression is associated with detrimental system-wide changes in patient tissue,
      which might govern patient survival even after successful elimination of tumour
      or cancerous cells.

PMID- 30205579
TI  - A Self-Adaptive Progressive Support Selection Scheme for Collaborative Wideband
      Spectrum Sensing.
AB  - The sampling rate of wideband spectrum sensing for sparse signals can be reduced
      by sub-Nyquist sampling with a Modulated Wideband Converter (MWC). In
      collaborative spectrum sensing, the fusion center recovers the spectral support
      from observation and measurement matrices reported by a network of CRs, to
      improve the precision of spectrum sensing. However, the MWC has a very high
      hardware complexity due to its parallel structure; it sets a fixed threshold for
      a decision without considering the impact of noise intensity, and needs a priori
      information of signal sparsity order for signal support recovery. To address
      these shortcomings, we propose a progressive support selection based self
      adaptive distributed MWC sensing scheme (PSS-SaDMWC). In the proposed scheme, the
      parallel hardware sensing channels are scattered on secondary users (SUs), and
      the PSS-SaDMWC scheme takes sparsity order estimation, noise intensity, and
      transmission loss into account in the fusion center. More importantly, the
      proposed scheme uses a support selection strategy based on a progressive
      operation to reduce missed detection probability under low SNR levels. Numerical
      simulations demonstrate that, compared with the traditional support selection
      schemes, our proposed scheme can achieve a higher support recovery success rate,
      lower sampling rate, and stronger time-varying support recovery ability without
      increasing hardware complexity.

PMID- 30205582
TI  - A Novel Parameter Estimation Method Based on a Tuneable Sigmoid in Alpha-Stable
      Distribution Noise Environments.
AB  - In this paper, a novel method, that employs a fractional Fourier transform and a
      tuneable Sigmoid transform, is proposed, in order to estimate the Doppler stretch
      and time delay of wideband echoes for a linear frequency modulation (LFM) pulse
      radar in an alpha-stable distribution noise environment. Two novel functions, a
      tuneable Sigmoid fractional correlation function (TS-FC) and a tuneable Sigmoid
      fractional power spectrum density (TS-FPSD), are presented in this paper. The
      novel algorithm based on the TS-FPSD is then proposed to estimate the Doppler
      stretch and the time delay. Then, the derivation of unbiasedness and consistency
      is presented. Furthermore, the boundness of the TS-FPSD to the symmetric alpha
      stable ( S alpha S ) noise, the parameter selection of the TS-FPSD, and the
      feasibility analysis of the TS-FPSD, are presented to evaluate the performance of
      the proposed method. In addition, the Cramer-Rao bound for parameter estimation
      is derived and computed in closed form, which shows that better performance has
      been achieved. Simulation results and theoretical analysis are presented, to
      demonstrate the applicability of the forgoing method. It is shown that the
      proposed method can not only effectively suppress impulsive noise interference,
      but it also does not need a priori knowledge of the noise with higher estimation
      accuracy in alpha-stable distribution noise environments.

PMID- 30205580
TI  - The Effects of Berberine on the Gut Microbiota in Apc min/+ Mice Fed with a High
      Fat Diet.
AB  - Background: Berberine (BBR) has been extensively reported to inhibit colorectal
      cancer (CRC) development, though its bioavailability is poor. Nowadays, an
      increasing number of studies have shown that BBR significantly accumulates in the
      intestines and could regulate gut microbiota in obesity. The purpose of this
      study was to further explore the effects of BBR on gut microbiota in Apc min/+
      mice receiving a high fat diet (HFD). Methods: Apc min/+ mice received either HFD
      alone or HFD and BBR for 12 weeks. The intestinal tissues were collected to
      evaluate the efficiency of BBR on neoplasm development by hematoxylin and eosin
      staining. Meanwhile, immunohistochemistry was conducted to investigate the
      effects of BBR on cyclin D1 and beta-catenin in colon tissues. Fecal samples were
      subjected to 16S rRNA sequencing. Results: BBR significantly reduced intestinal
      tumor development and altered the structure of gut microbiota in Apc min/+ mice
      fed with an HFD. At the phylum level, it was able to significantly inhibit the
      increase in Verrucomicrobia. At the genus level, it was able to suppress
      Akkermansia and elevate some short chain fat acid (SCFA)-producing bacteria.
      Conclusions: BBR significantly alleviated the development of CRC in Apc min/+
      mice fed with HFD and restored the enteric microbiome community.

PMID- 30205581
TI  - Seasonal Allergies and Psychiatric Disorders in the United States.
AB  - Seasonal allergies have been associated with mental health problems, though the
      evidence is still emergent, particularly in the United States. We analyzed data
      from the National Comorbidity Survey Replication and the National Latino and
      Asian American Survey (years 2001-2003). Multivariable logistic regression models
      were used to examine the relations between lifetime allergies and lifetime
      psychiatric disorders (each disorder in a separate model), adjusting for socio
      demographic variables (including region of residence) and tobacco use. Analyses
      were also stratified to test for effect modification by race and sex. A history
      of seasonal allergies was associated with greater odds of mood disorders, anxiety
      disorders, and eating disorders, but not alcohol or substance use disorders,
      after adjusting for socio-demographic characteristics and tobacco use. The
      associations between seasonal allergies and mood disorders, substance use
      disorders, and alcohol use disorders were particularly strong for Latino
      Americans. The association between seasonal allergies and eating disorders was
      stronger for men than women. Seasonal allergies are a risk factor for psychiatric
      disorders. Individuals complaining of seasonal allergies should be screened for
      early signs of mental health problems and referred to specialized services
      accordingly.

PMID- 30205583
TI  - Utilization of DES-Lignin as a Bio-Based Hydrophilicity Promoter in the
      Fabrication of Antioxidant Polyethersulfone Membranes.
AB  - Enhancement of membrane permeability at no detriment of its other performances,
      e.g., selectivity, is a goal-directed objective in membrane fabrication. A novel
      antioxidant DES-lignin (lignin extracted from birch wood by using a deep eutectic
      solvent) polyethersulfone (PES) membrane, containing 0-1 wt % DES-lignin, was
      fabricated with the phase inversion technique. The performance and morphology of
      the fabricated membranes were characterized by a pure water flux, polyethylene
      glycol (PEG) retention, Fourier transform infrared spectroscopy, scanning
      electron microscopy, and contact angle measurements. Membranes with less negative
      charge and better hydrophilicity were obtained when the DES-lignin content in the
      polymer solution was increased. With the highest dosage, the incorporation of DES
      lignin in the membrane matrix improved the membrane permeability by 29.4%
      compared to a pure PES membrane. Moreover, no leakage of DES-lignin from the
      membrane structure was observed, indicating good compatibility of DES-lignin with
      the PES structure. It was also found that the improvement of both rejection and
      pure water flux could be achieved by using a small dosage of DES-lignin (0.25 wt
      %) in membrane fabrication. The membranes incorporated with DES-lignin showed
      higher DPPH (2,2-diphenyl-1-picrylhydrazyl) and ABTS (2,2-Azino-bis (3
      ethylbenzothiazoline-6-sulfonic acid)) scavenging activity compared to the pure
      membrane, where 2.6 and 1.1 times higher DPPH and ABTS scavenging activity was
      observed with the highest DES-lignin content (1 wt %). Thus, the results of this
      study demonstrate well the feasibility of utilizing DES-lignin as an antioxidant
      bio-based hydrophilicity promoter in the fabrication of ultrafiltration
      membranes.

PMID- 30205584
TI  - Mediterranean Wild Edible Plants: Weeds or "New Functional Crops"?
AB  - The Mediterranean basin is a biodiversity hotspot of wild edible species, and
      their therapeutic and culinary uses have long been documented. Owing to the
      growing demand for wild edible species, there are increasing concerns about the
      safety, standardization, quality, and availability of products derived from these
      species collected in the wild. An efficient cultivation method for the species
      having promising nutraceutical values is highly desirable. In this backdrop, a
      hydroponic system could be considered as a reproducible and efficient agronomic
      practice to maximize yield, and also to selectively stimulate the biosynthesis of
      targeted metabolites. The aim of this report is to review the phytochemical and
      toxic compounds of some potentially interesting Mediterranean wild edible
      species. Herein, after a deep analysis of the literature, information on the main
      bioactive compounds, and some possibly toxic molecules, from fifteen wild edible
      species have been compiled. The traditional recipes prepared with these species
      are also listed. In addition, preliminary data about the performance of some
      selected species are also reported. In particular, germination tests performed on
      six selected species revealed that there are differences among the species, but
      not with crop species. "Domestication" of wild species seems a promising approach
      for exploiting these "new functional foods".

PMID- 30205585
TI  - Myalgic Encephalomyelitis (ME) or What? An Operational Definition.
AB  - Myalgic encephalomyelitis (ME), identified as a new clinical entity with
      distinctive features in 1956, was originally considered as a neuromuscular
      disease. In 1988 the Centers for Disease Control and Prevention introduced the
      ill-defined concept of chronic fatigue syndrome (CFS). As predicted, CFS,
      unjustly considered to be a synonym for ME, pushed ME to the background. To
      develop effective therapies for of ME and CFS, it is essential to investigate
      patients with ME specifically. For that reason, an operational definition of ME
      is indispensable. This article proposes an operational definition based on the
      most recent formal definitions and symptoms observed in ME. ME is a multi
      systemic illness, which (1) often has a sudden onset, in most cases a respiratory
      and/or gastro-intestinal infection, but a gradual or more dramatic onset is also
      possible; (2) has an epidemic and an endemic form; (3) has an unique clinical
      pattern deviating from other post-viral states; (4) is distinguished by muscle
      fatigability/prolonged muscle weakness after trivial exertion; (5) is accompanied
      by symptoms relating to neurological disturbance, especially of cognitive,
      autonomic, and sensory functions; (6) can be accompanied by symptoms associated
      with cardiac and other systems; (7) is characterized by fluctuation of symptoms
      (within and between "episodes"); (8) has a prolonged relapsing course; and (9)
      has a tendency to become chronic. In conclusion, a discriminative definition for
      ME contains four mandatory elements: (1) muscle fatigability/post-exertional
      muscle weakness lasting for days; (2) operational criteria for "neurological
      disturbance, especially of cognitive, autonomic and sensory functions"; (3)
      fluctuation of symptoms; and (4) a prolonged relapsing course. This tentative
      definition of ME justifies the qualification "neuromuscular disease".

PMID- 30205586
TI  - Characteristics of Invasive Fungal Infections among HIV Individuals from an
      Indigenous Origin in Mexico.
AB  - In individuals with HIV/AIDS, 47% of the deaths are attributed to invasive fungal
      infections (IFIs), despite antiretroviral (ARV) therapy. This is a retrospective
      study carried out in the Hospital Regional de Alta Especialidad Oaxaca (HRAEO),
      southwest Mexico, where IFIs that occurred during 2016-2017 are described. A
      total of 55 individuals were included. Histoplasmosis (36%) and possible-IFIs in
      neutropenic fever (20%) were the most frequent cases, followed by cryptococcosis
      (14%). The HIV/AIDS subpopulation corresponded with 26 cases (47%), all from an
      indigenous origin. The incidence of IFIs among them was 24% (95% CI = 15-33%).
      The CD4+ T cells median was 35 cells/mL (IQR 12-58). Four cases (15%) of
      unmasking IRIS were identified, three of histoplasmosis and one
      coccidioidomycosis. Co-infections were found in 52% (12/23), and tuberculosis in
      50% (6/12) was the most frequent. The mortality rate was 48%. The general
      characteristics of the HIV individuals who died were atypical pneumonia (70% vs.
      9%, p = 0.01), acute kidney injury, (70% vs. 9%, p = 0.008) and ICU stay (80% vs.
      9%, p = 0.002). In conclusion, IFIs are diagnosed in one out of four individuals
      with HIV/AIDS along with other complicated infectious conditions, leading to
      major complications and a high mortality rate.

PMID- 30205587
TI  - Do Progestin-Only Contraceptives Contribute to the Risk of Developing Depression
      as Implied by Beta-Arrestin 1 Levels in Leukocytes? A Pilot Study.
AB  - We reported previously that reduction in beta-arrestin 1 (beta-AR 1) protein
      levels in peripheral blood mononuclear leukocytes (PBMC) significantly correlated
      with the severity of depressive symptoms in reproductive women. In this pilot
      study, we used beta-AR 1 protein levels in PBMC as a marker for developing
      depressive symptoms and the Hamilton Depression Rating Scale (HAM-D) scores to
      assess potential mood-related side effects of oral contraceptive use for routine
      birth control among women. We evaluated 29 women in this study. We enrolled the
      participants in three groups: Estrogen-progestin combination-oral contraceptives
      (COC, n = 10), progestin-only contraceptives (POC, n = 12), and non-hormonal or
      no contraceptives (NC, n = 7). We determined the beta-AR 1 protein levels in
      PBMCs by enzyme-linked immunosorbent assay (ELISA). We found that women in the
      POC group had significantly higher HAM-D scores compared to those in the COC (p <
      0.0004) and NC (p < 0.004). The levels of beta-AR 1 protein were significantly
      attenuated in women in the POC group compared to women in the NC group (p =
      0.03). Our findings suggest that the use of POC is a potential risk factor for
      developing depressive symptoms.

PMID- 30205589
TI  - Surface Modification of Calcium Silicate via Mussel-Inspired Polydopamine and
      Effective Adsorption of Extracellular Matrix to Promote Osteogenesis
      Differentiation for Bone Tissue Engineering.
AB  - Calcium silicate-based cement has garnered huge interest in recent years, due to
      its versatility and potential in mass fabrication of a variety of bioceramics.
      For this study, the main objective was to fabricate functionalized calcium
      silicate (CS) powder integrated with a simple bio-inspired surface modification
      using polydopamine (PDA), to regulate cellular behaviors such as cellular
      adhesion, and subsequently cell differentiation and proliferation. For this
      study, scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy
      (XPS) techniques were used to analyze the chemical compositions and observe the
      surface characteristics of our PDA coated CS cements. Such modifications were
      found to enhance Wharton Jelly's mesenchymal stem cells (WJMSC) in various ways.
      Firstly, PDA-coated CS cements were found to significantly enhance cell adhesion
      with higher expressions of cell adhesion markers, such as focal adhesion kinase
      and integrins. This was further supported by morphology analysis of the cells.
      This enhanced cell adhesion, in turn, led to significantly higher secretion of
      extracellular matrix (ECM) proteins, such as collagen I and fibronectin, which
      directly promoted cell attachments and proliferation. In our osteogenesis assays,
      it was found that secretion and expression of osteogenesis related genes and
      proteins were significantly higher and were dependent on the PDA content.
      Therefore, these results demonstrated that such simple bio-inspired modification
      techniques of synthetic degradable CS cements can be applied as a future
      modification, to modify and convert inert surfaces of synthetic bone grafts to
      enhance and modulate the cell behaviors of WJMSCs. This in turn can be used as a
      potential alternative for further bioengineering research.

PMID- 30205590
TI  - Mechanical Properties and In Situ Deformation Imaging of Microlattices
      Manufactured by Laser Based Powder Bed Fusion.
AB  - This paper reports on the production and mechanical properties of Ti6Al4V
      microlattice structures with strut thickness nearing the single-track width of
      the laser-based powder bed fusion (LPBF) system used. Besides providing new
      information on the mechanical properties and manufacturability of such thin-strut
      lattices, this paper also reports on the in situ deformation imaging of
      microlattice structures with six unit cells in every direction. LPBF lattices are
      of interest for medical implants due to the possibility of creating structures
      with an elastic modulus close to that of the bones and small pore sizes that
      allow effective osseointegration. In this work, four different cubes were
      produced using laser powder bed fusion and subsequently analyzed using microCT,
      compression testing, and one selected lattice was subjected to in situ microCT
      imaging during compression. The in situ imaging was performed at four steps
      during yielding. The results indicate that mechanical performance (elastic
      modulus and strength) correlate well with actual density and that this
      performance is remarkably good despite the high roughness and irregularity of the
      struts at this scale. In situ yielding is visually illustrated.

PMID- 30205591
TI  - Advantages of the Surface Structuration of KBr Materials for Spectrometry and
      Sensors.
AB  - A potassium bromide (KBr) material, which has been widely used as the key element
      in Fourier spectrometers and as the output window of the IR-lasers, was studied
      via applying carbon nanotubes in order to modify the potassium bromide surface.
      The laser-oriented deposition method was used to place the carbon nanotubes at
      the matrix material surface in the vertical position at different electric fields
      varying from 100 to 600 V * cm-1. The main idea of the improvement of the
      spectral properties of the potassium bromide structure is connected with the fact
      that the refractive index of the carbon nanotubes is substantially less than the
      refractive index of the studied material, and the small diameter of the carbon
      nanotubes allows one to embed these nano-objects in the voids of the lattice of
      the model matrix systems. Moreover, the mechanical characteristics and wetting
      features of potassium bromide structures have been investigated under the
      condition mentioned above. Analytical and quantum-chemical simulations have
      supported the experimental results.

PMID- 30205588
TI  - Characterization of vB_Kpn_F48, a Newly Discovered Lytic Bacteriophage for
      Klebsiella pneumoniae of Sequence Type 101.
AB  - Resistance to carbapenems in Enterobacteriaceae, including Klebsiella pneumoniae,
      represents a major clinical problem given the lack of effective alternative
      antibiotics. Bacteriophages could provide a valuable tool to control the
      dissemination of antibiotic resistant isolates, for the decolonization of
      colonized individuals and for treatment purposes. In this work, we have
      characterized a lytic bacteriophage, named vB_Kpn_F48, specific for K. pneumoniae
      isolates belonging to clonal group 101. Phage vB_Kpn_F48 was classified as a
      member of Myoviridae, order Caudovirales, on the basis of transmission electron
      microscopy analysis. Physiological characterization demonstrated that vB_Kpn_F48
      showed a narrow host range, a short latent period, a low burst size and it is
      highly stable to both temperature and pH variations. High throughput sequencing
      and bioinformatics analysis revealed that the phage is characterized by a 171 Kb
      dsDNA genome that lacks genes undesirable for a therapeutic perspective such
      integrases, antibiotic resistance genes and toxin encoding genes. Phylogenetic
      analysis suggests that vB_Kpn_F48 is a T4-like bacteriophage which belongs to a
      novel genus within the Tevenvirinae subfamily, which we tentatively named
      "F48virus". Considering the narrow host range, the genomic features and overall
      physiological parameters phage vB_Kpn_F48 could be a promising candidate to be
      used alone or in cocktails for phage therapy applications.

PMID- 30205592
TI  - Antiviral Activities of Oleanolic Acid and Its Analogues.
AB  - Viral diseases, such as human immune deficiency virus (HIV), influenza,
      hepatitis, and herpes, are the leading causes of human death in the world. The
      shortage of effective vaccines or therapeutics for the prevention and treatment
      of the numerous viral infections, and the great increase in the number of new
      drug-resistant viruses, indicate that there is a great need for the development
      of novel and potent antiviral drugs. Natural products are one of the most
      valuable sources for drug discovery. Most natural triterpenoids, such as
      oleanolic acid (OA), possess notable antiviral activity. Therefore, it is
      important to validate how plant isolates, such as OA and its analogues, can
      improve and produce potent drugs for the treatment of viral disease. This article
      reports a review of the analogues of oleanolic acid and their selected pathogenic
      antiviral activities, which include HIV, the influenza virus, hepatitis B and C
      viruses, and herpes viruses.

PMID- 30205594
TI  - Terpenoids from Marine Soft Coral of the Genus Lemnalia: Chemistry and Biological
      Activities.
AB  - Lemnalia is one of the most widely-distributed marine soft coral in tropical
      oceans and is known to produce novel terpenoids with a broad spectrum of
      biological activities. This review provides the first comprehensive overview of
      terpenoids produced by soft coral Lemnalia since their first discovery in 1974.

PMID- 30205593
TI  - The RNA Capping Enzyme Domain in Protein A is Essential for Flock House Virus
      Replication.
AB  - The nodavirus flock house virus (FHV) and the alphavirus Semliki Forest virus
      (SFV) show evolutionarily intriguing similarities in their replication complexes
      and RNA capping enzymes. In this study, we first established an efficient FHV
      trans-replication system in mammalian cells, which disjoins protein expression
      from viral RNA synthesis. Following transfection, FHV replicase protein A was
      associated with mitochondria, whose outer surface displayed pouch-like
      invaginations with a 'neck' structure opening towards the cytoplasm. In
      mitochondrial pellets from transfected cells, high-level synthesis of both
      genomic and subgenomic RNA was detected in vitro and the newly synthesized RNA
      was of positive polarity. Secondly, we initiated the study of the putative RNA
      capping enzyme domain in protein A by mutating the conserved amino acids H93,
      R100, D141, and W215. RNA replication was abolished for all mutants inside cells
      and in vitro except for W215A, which showed reduced replication. Transfection of
      capped RNA template did not rescue the replication activity of the mutants.
      Comparing the efficiency of SFV and FHV trans-replication systems, the FHV system
      appeared to produce more RNA. Using fluorescent marker proteins, we demonstrated
      that both systems could replicate in the same cell. This work may facilitate the
      comparative analysis of FHV and SFV replication.

PMID- 30205596
TI  - The Physicochemical Properties of Decellularized Extracellular Matrix-Coated 3D
      Printed Poly(epsilon-caprolactone) Nerve Conduits for Promoting Schwann Cells
      Proliferation and Differentiation.
AB  - Although autologous nerve grafting remains the gold standard treatment for
      peripheral nerve injuries, alternative methods such as development of nerve
      guidance conduits have since emerged and evolved to counter the many
      disadvantages of nerve grafting. However, the efficacy and viability of current
      nerve conduits remain unclear in clinical trials. Here, we focused on a novel
      decellularized extracellular matrix (dECM) and polydopamine (PDA)-coated 3D
      printed poly(epsilon-caprolactone) (PCL)-based conduits, whereby the PDA surface
      modification acts as an attachment platform for further dECM attachment. We
      demonstrated that dECM/PDA-coated PCL conduits possessed higher mechanical
      properties when compared to human or animal nerves. Such modifications were
      proved to affect cell behaviors. Cellular behaviors and neuronal differentiation
      of Schwann cells were assessed to determine for the efficacies of the conduits.
      There were some cell-specific neuronal markers, such as Nestin, neuron-specific
      class III beta-tubulin (TUJ-1), and microtubule-associated protein 2 (MAP2)
      analyzed by enzyme-linked immunosorbent assay, and Nestin expressions were found
      to be 0.65-fold up-regulated, while TUJ1 expressions were 2.3-fold up-regulated
      and MAP2 expressions were 2.5-fold up-regulated when compared to Ctl. The
      methodology of PDA coating employed in this study can be used as a simple model
      to immobilize dECM onto PCL conduits, and the results showed that dECM/PDA-coated
      PCL conduits can as a practical and clinically viable tool for promoting
      regenerative outcomes in larger peripheral nerve defects.

PMID- 30205595
TI  - Resveratrol: A Double-Edged Sword in Health Benefits.
AB  - Resveratrol (3,5,4'-trihydroxy-trans-stilbene) belongs to polyphenols'
      stilbenoids group, possessing two phenol rings linked to each other by an
      ethylene bridge. This natural polyphenol has been detected in more than 70 plant
      species, especially in grapes' skin and seeds, and was found in discrete amounts
      in red wines and various human foods. It is a phytoalexin that acts against
      pathogens, including bacteria and fungi. As a natural food ingredient, numerous
      studies have demonstrated that resveratrol possesses a very high antioxidant
      potential. Resveratrol also exhibit antitumor activity, and is considered a
      potential candidate for prevention and treatment of several types of cancer.
      Indeed, resveratrol anticancer properties have been confirmed by many in vitro
      and in vivo studies, which shows that resveratrol is able to inhibit all
      carcinogenesis stages (e.g., initiation, promotion and progression). Even more,
      other bioactive effects, namely as anti-inflammatory, anticarcinogenic,
      cardioprotective, vasorelaxant, phytoestrogenic and neuroprotective have also
      been reported. Nonetheless, resveratrol application is still being a major
      challenge for pharmaceutical industry, due to its poor solubility and
      bioavailability, as well as adverse effects. In this sense, this review
      summarized current data on resveratrol pharmacological effects.

PMID- 30205598
TI  - The Role of the Primary Cell Wall in Plant Morphogenesis.
AB  - Morphogenesis remains a riddle, wrapped in a mystery, inside an enigma. It
      remains a formidable problem viewed from many different perspectives of
      morphology, genetics, and computational modelling. We propose a biochemical
      reductionist approach that shows how both internal and external physical forces
      contribute to plant morphogenesis via mechanical stress-strain transduction from
      the primary cell wall tethered to the plasma membrane by a specific
      arabinogalactan protein (AGP). The resulting stress vector, with direction
      defined by Hechtian adhesion sites, has a magnitude of a few piconewtons
      amplified by a hypothetical Hechtian growth oscillator. This paradigm shift
      involves stress-activated plasma membrane Ca2+ channels and auxin-activated H+
      ATPase. The proton pump dissociates periplasmic AGP-glycomodules that bind Ca2+.
      Thus, as the immediate source of cytosolic Ca2+, an AGP-Ca2+ capacitor directs
      the vectorial exocytosis of cell wall precursors and auxin efflux (PIN) proteins.
      In toto, these components comprise the Hechtian oscillator and also the
      gravisensor. Thus, interdependent auxin and Ca2+ morphogen gradients account for
      the predominance of AGPs. The size and location of a cell surface AGP-Ca2+
      capacitor is essential to differentiation and explains AGP correlation with all
      stages of morphogenetic patterning from embryogenesis to root and shoot. Finally,
      the evolutionary origins of the Hechtian oscillator in the unicellular
      Chlorophycean algae reflect the ubiquitous role of chemiosmotic proton pumps that
      preceded DNA at the dawn of life.

PMID- 30205599
TI  - Maternal Iodine Status is Associated with Offspring Language Skills in Infancy
      and Toddlerhood.
AB  - Inadequate iodine status affects the synthesis of the thyroid hormones and may
      impair brain development in fetal life. The aim of this study was to explore the
      association between maternal iodine status in pregnancy measured by urinary
      iodine concentration (UIC) and child neurodevelopment at age 6, 12 and 18 months
      in a population-based cohort. In total, 1036 families from nine locations in
      Norway were enrolled in the little in Norway cohort. The present study includes n
      = 851 mother-child pairs with singleton pregnancies, no use of thyroid medication
      in pregnancy, no severe genetic disorder, data on exposure (UIC) in pregnancy and
      developmental outcomes (Bayley Scales of Infant and Toddler Development, third
      edition). Data collection also included general information from questionnaires.
      We examined associations between UIC (and use of iodine-containing supplements)
      and repeated measures of developmental outcomes using multivariable mixed models.
      The median UIC in pregnancy was 78 ug/L (IQR 46-130), classified as insufficient
      iodine intake according to the WHO. Eighteen percent reported use of iodine
      containing multisupplements. A UIC below ~100 was associated with reduced
      receptive (p = 0.025) and expressive language skills (p = 0.002), but not with
      reduced cognitive or fine- and gross motor skills. Maternal use of iodine
      containing supplements was associated with lower gross motor skills (b = -0.18,
      95% CI = -0.33, -0.03, p = 0.02), but not with the other outcome measures. In
      conclusion, an insufficient iodine intake in pregnancy, reflected in a UIC below
      ~100 ug/L, was associated with lower infant language skills up to 18 months. The
      use of iodine-containing supplements was not associated with beneficial effects.

PMID- 30205600
TI  - High Performance of Covalently Grafting onto Collagen in The Presence of Graphene
      Oxide.
AB  - A collagen-based copolymer, ASC-g-Poly(methyl methacrylate-co-Ethyl Acrylate),
      was synthesized in the presence of Graphene Oxide (GO) via an in-situ
      polymerization. The presence of GO that increased the accessible surface area for
      initiated collagen chains allowed for an accelerated polymerization with highly
      improved grafting performance and efficiency. This was conducted from two
      polymerization systems with varied comonomer feed ratios, in which two
      distinguished GO loadings were used. The processability of the achieved
      nanocomposite was then evaluated through casting and electrospinning processing
      methods. Fourier Transform Infrared Spectroscopy (FT-IR), UV-Vis spectroscopy,
      Differential Scanning Calorimeter (DSC), Thermogravimetric analysis (TGA),
      Scanning Electron Microscope (SEM), Transmission electron microscopy (TEM), and
      tensile analysis were conducted to characterize the GO-ASC-g-P(MMA-co-EA). The
      nanocomposite films showed a unique morphology, multilayer nanostructure of the
      grafted GO monolayers that deposited simultaneously one on top of another. The
      morphology of the electrospun fibers was affected by the addition of GO loadings
      in which the increase in fiber diameter was observed while the surface of the
      nanofibers was decorated by the GO nanolayers. To modify the collagen, this
      research highlights the importance of introducing functional groups of GO and the
      substitution of GO loadings as an active nanostructure filler to highly monomer
      feed ratios improving the physiochemical properties of collagen. This easy-to
      apply approach is suggested for applications intending the mechanical properties
      and deterred degradation of Collagen-based materials.

PMID- 30205597
TI  - Unraveling the Molecular Determinants of Manual Therapy: An Approach to
      Integrative Therapeutics for the Treatment of Fibromyalgia and Chronic Fatigue
      Syndrome/Myalgic Encephalomyelitis.
AB  - Application of protocols without parameter standardization and appropriate
      controls has led manual therapy (MT) and other physiotherapy-based approaches to
      controversial outcomes. Thus, there is an urgency to carefully define standard
      protocols that elevate physiotherapy treatments to rigorous scientific demands.
      One way in which this can be achieved is by studying gene expression and
      physiological changes that associate to particular, parameter-controlled,
      treatments in animal models, and translating this knowledge to properly designed,
      objective, quantitatively-monitored clinical trials (CTs). Here, we propose a
      molecular physiotherapy approach (MPTA) requiring multidisciplinary teams, to
      uncover the scientific reasons behind the numerous reports that historically
      attribute health benefits to MT-treatments. The review focuses on the
      identification of MT-induced physiological and molecular responses that could be
      used for the treatment of fibromyalgia (FM) and chronic fatigue syndrome/myalgic
      encephalomyelitis (CFS/ME). The systemic effects associated to mechanical-load
      responses are considered of particular relevance, as they suggest that defined,
      low-pain anatomic areas can be selected for MT treatment and yet yield overall
      benefits, an aspect that might result in it being essential to treat FM.
      Additionally, MT can provide muscle conditioning to sedentary patients without
      demanding strenuous physical effort, which is particularly detrimental for CFS/ME
      patients, placing MT as a real option for integrative medicine programs to
      improve FM and CFS/ME.

PMID- 30205601
TI  - The Prevalence of Vitamin A Deficiency and Associated Factors in Pregnant Women
      Receiving Prenatal Care at a Reference Maternity Hospital in Northeastern Brazil.
AB  - Vitamin A is essential for mother and child; however, vitamin A deficiency (VAD)
      remains a public health issue in various countries, affecting around 19 million
      pregnant women. In Brazil, the scarcity and inconsistency of data have prevented
      the prevalence and epidemiological status of VAD from being established. This
      study aimed to analyze vitamin A nutritional status in women receiving prenatal
      care at a reference center in northeastern Brazil. A cross-sectional study was
      conducted with a sample of 676 women. Serum retinol was measured by high
      performance liquid chromatography. Subclinical infection was detected by
      measuring C-reactive protein (CRP). The World Health Organization criteria were
      used in the prevalence analysis, VAD classification level, and CRP effect
      evaluation. The prevalence of VAD (serum retinol <0.70 MUmol/L) was 6.2% (95%
      confidence interval 4.5-8.3). In the univariate analysis, the variables
      significantly associated with VAD (p < 0.05) were having <12 years of schooling,
      being in the third trimester of pregnancy, and anemia. In the final multivariate
      model, the variables that remained significantly associated (p < 0.05) were being
      in the third trimester of pregnancy and anemia. VAD constituted a mild public
      health problem in this sample of pregnant women and was associated with the third
      trimester of pregnancy and maternal anemia.

PMID- 30205602
TI  - Dietary Cholesterol Contained in Whole Eggs Is Not Well Absorbed and Does Not
      Acutely Affect Plasma Total Cholesterol Concentration in Men and Women: Results
      from 2 Randomized Controlled Crossover Studies.
AB  - Whole egg is a food source of dietary cholesterol and inconsistent research
      findings exist about the effect of dietary cholesterol from whole egg on blood
      cholesterol concentration. We assessed the effect of co-consuming cooked whole
      egg (CWE) on dietary cholesterol absorption from two randomized-crossover
      studies. For study 1, 16 men consumed raw vegetables with no egg, 75 g CWE, or
      150 g CWE. For study 2, 17 women consumed cooked vegetables with no egg or 100 g
      CWE. Triacylglycerol-rich lipoprotein fractions (TRL) were isolated from
      collected blood. In study 1, total-cholesterol areas under the curve (AUC)0-10h
      in TRL were not different but triacylglycerol AUC0-10h in TRL was greater for 150
      g CWE vs. 75 g CWE and no egg. Similarly, in study 2, total-cholesterol AUC0-10h
      in TRL was not different but triacylglycerol AUC0-10h in TRL was greater for 100
      g CWE vs. no egg. In both studies, whole egg consumption did not affect plasma
      total-cholesterol AUC0-10h, while triacylglycerol AUC0-10h was increased. These
      results suggest that the dietary cholesterol in whole egg was not well absorbed,
      which may provide mechanistic insight for why it does not acutely influence
      plasma total-cholesterol concentration and is not associated with longer-term
      plasma cholesterol control.

PMID- 30205604
TI  - Chemical Interaction-Induced Evolution of Phase Compatibilization in Blends of
      Poly(hydroxy ether of bisphenol-A)/Poly(1,4-butylene terephthalate).
AB  - An immiscible blend of poly(hydroxy ether of bisphenol-A) (phenoxy) and poly(1,4
      butylene terephthalate) (PBT) with phase separation was observed in as-blended
      samples. The compatibilization of phenoxy/PBT blends can be promoted through
      chemical exchange reactions of phenoxy with PBT upon annealing. The annealed
      phenoxy/PBT blends had a homogeneous phase with a single Tg that could be
      enhanced by annealing at 260  degrees C. Infrared (IR) spectroscopy demonstrated
      that phase homogenization could be promoted by annealing the phenoxy/PBT blend,
      where alcoholytic exchange occurred between the dangling hydroxyl group (-OH) in
      phenoxy and the carbonyl group (C=O) in PBT in the heated blends. The alcoholysis
      reaction changed the aromatic linkages to aliphatic linkages in the carbonyl
      groups, which initially led to the formation of a graft copolymer of phenoxy and
      PBT with an aliphatic/aliphatic carbonyl link. The progressive alcoholysis
      reaction resulted in the transformation of the initial homopolymers into block
      copolymers and finally into random copolymers, which promoted phase
      compatibilization in blends of phenoxy with PBT. As the amount of copolymers
      increased upon annealing, the crystallization of PBT was inhibited by alcoholytic
      exchange in the blends.

PMID- 30205603
TI  - Can Intradetrusor OnabotulinumtoxinA Injections Alter Heart Function in Patients
      with Cardiac Arrhythmia?
AB  - The prevalence of overactive bladder (OAB) increases with age and can be
      associated with other co-morbidities, such as cardiac arrhythmia. Unfortunately,
      commonly used anticholinergic drugs for OAB can affect the cardiovascular system,
      leading to tachycardia. However, there are no data, which consider the influence
      of intradetrusor onabotulinumtoxinA injections on heart function in idiopathic
      OAB patients. The aim of the present study was to evaluate the influence of
      intradetrusor onabotulinumtoxinA injections on electrocardiogram (ECG)
      parameters. Additionally, changes in ECG were analyzed in OAB patients without
      cardiac arrhythmia. Thirty-one patients with cardiac arrhythmia and 31
      participants without irregular heart rate (HR) completed the study. ECG
      measurements were performed in supine positions 2 h before onabotulinumtoxinA
      injections, 1 h after treatment, and at 2 weeks of follow-up. At week 6, a phone
      call survey was conducted to collect data about adverse events.
      OnabotulinumtoxinA injections were performed with rigid cystoscopy under local
      anesthesia. We did not observe any clinically significant changes in the analyzed
      ECG parameters between consecutive measurements. While a slight increase of HR
      was observed in patients without cardiac arrhythmia, it remained within normal
      range. Intravesical onabotulinumtoxinA injections are, hence, safe for female
      patients with cardiac arrhythmia and do not significantly influence changes in
      ECG.

PMID- 30205606
TI  - Metformin Decreases Risk of Tuberculosis Infection in Type 2 Diabetes Patients.
AB  - BACKGROUND: Metformin may show an antibiotic effect, but whether its use can
      reduce the risk of tuberculosis infection has rarely been investigated in
      population-based studies. METHODS: This is a retrospective cohort analysis of the
      Taiwan's National Health Insurance database. New-onset type 2 diabetes patients,
      148,468 ever users and 15,799 never users of metformin, identified during 1999
      2005 were followed up until 31 December 2011 for the incidence of tuberculosis
      infection. Hazard ratios were estimated by Cox regression incorporated with the
      inverse probability of treatment weighting using propensity score. RESULTS: A
      total of 360 never users and 1976 ever users developed a tuberculosis infection
      with respective incidence of 510.91 and 282.94 per 100,000 person-years. The
      overall hazard ratio of presenting a tuberculosis infection among metformin ever
      users in respect to never users was 0.552 (95% confidence interval: 0.493-0.617).
      The hazard ratios for the first (<27.10 months), second (27.10-58.27 months), and
      third (>58.27 months) tertile of cumulative duration of metformin therapy were
      1.116 (0.989-1.261), 0.543 (0.478-0.618), and 0.200 (0.171-0.233), respectively;
      and were 1.037 (0.918-1.173), 0.533 (0.469-0.606), and 0.249 (0.215-0.288),
      respectively, for the first (<817,000 mg), second (817,000-2,047,180 mg), and
      third (>2,047,180 mg) tertile of cumulative doses of metformin. The findings were
      consistent when analyses were restricted to pulmonary tuberculosis. Additionally,
      regular users of metformin tended to have greater benefit than irregular users.
      CONCLUSIONS: Metformin use is associated with a reduced risk of tuberculosis
      infection in a dose-response pattern in type 2 diabetes patients.

PMID- 30205605
TI  - Mesomorphic Behavior in Silver(I) N-(4-Pyridyl) Benzamide with Aromatic pi-pi
      Stacking Counterions.
AB  - Organic semiconductor materials composed of pi-pi stacking aromatic compounds
      have been under intense investigation for their potential uses in flexible
      electronics and other advanced technologies. Herein we report a new family of
      seven pi-pi stacking compounds of silver(I) bis-N-(4-pyridyl) benzamide with
      varying counterions, namely [Ag(NPBA)2]X, where NPBA is N-(4-pyridyl) benzamine,
      X = NO3- (1), ClO4- (2), CF3SO3- (3), PF6- (4), BF4- (5), CH3PhSO3- (6), and
      PhSO3- (7), which form extended pi-pi stacking networks in one-dimensional (1D),
      2D and 3D directions in the crystalline solid-state via the phenyl moiety, with
      average inter-ring distances of 3.823 A. Interestingly, the counterions that
      contain pi-pi stacking-capable groups, such as in 6 and 7, can induce the
      formation of mesomorphic phases at 130  degrees C in dimethylformamide (DMF), and
      can generate highly branched networks at the mesoscale. Atomic force microscopy
      studies showed that 2D interconnected fibers form right after nucleation, and
      they extend from ~30 nm in diameter grow to reach the micron scale, which
      suggests that it may be possible to stop the process in order to obtain
      nanofibers. Differential scanning calorimetry studies showed no remarkable
      thermal behavior in the complexes in the solid state, which suggests that the
      mesomorphic phases originate from the mechanisms that occur in the DMF solution
      at high temperatures. An all-electron level simulation of the band gaps using
      NRLMOL (Naval Research Laboratory Molecular Research Library) on the crystals
      gave 3.25 eV for (1), 3.68 eV for (2), 1.48 eV for (3), 5.08 eV for (4), 1.53 eV
      for (5), and 3.55 eV for (6). Mesomorphic behavior in materials containing pi-pi
      stacking aromatic interactions that also exhibit low-band gap properties may pave
      the way to a new generation of highly branched organic semiconductors.

PMID- 30205607
TI  - Non-Contact Body Measurement for Qinchuan Cattle with LiDAR Sensor.
AB  - The body dimension measurement of large animals plays a significant role in
      quality improvement and genetic breeding, and the non-contact measurements by
      computer vision-based remote sensing could represent great progress in the case
      of dangerous stress responses and time-costing manual measurements. This paper
      presents a novel approach for three-dimensional digital modeling of live adult
      Qinchuan cattle for body size measurement. On the basis of capturing the original
      point data series of live cattle by a Light Detection and Ranging (LiDAR) sensor,
      the conditional, statistical outliers and voxel grid filtering methods are fused
      to cancel the background and outliers. After the segmentation of K-means
      clustering extraction and the RANdom SAmple Consensus (RANSAC) algorithm, the
      Fast Point Feature Histogram (FPFH) is put forward to get the cattle data
      automatically. The cattle surface is reconstructed to get the 3D cattle model
      using fast Iterative Closest Point (ICP) matching with Bi-directional Random K-D
      Trees and a Greedy Projection Triangulation (GPT) reconstruction method by which
      the feature points of cattle silhouettes could be clicked and calculated.
      Finally, the five body parameters (withers height, chest depth, back height, body
      length, and waist height) are measured in the field and verified within an
      accuracy of 2 mm and an error close to 2%. The experimental results show that
      this approach could be considered as a new feasible method towards the non
      contact body measurement for large physique livestock.

PMID- 30205608
TI  - Noncontact Strain Monitoring of Osseointegrated Prostheses.
AB  - The objective of this study was to develop a noncontact, noninvasive, imaging
      system for monitoring the strain and deformation states of osseointegrated
      prostheses. The proposed sensing methodology comprised of two parts. First, a
      passive thin film was designed such that its electrical permittivity increases in
      tandem with applied tensile loading and decreases while unloading. It was found
      that patterning the thin films could enhance their dielectric property's
      sensitivity to strain. The film can be deposited onto prosthesis surfaces as an
      external coating prior to implant. Second, an electrical capacitance tomography
      (ECT) measurement technique and reconstruction algorithm were implemented to
      capture strain-induced changes in the dielectric property of nanocomposite-coated
      prosthesis phantoms when subjected to different loading scenarios. The
      preliminary results showed that ECT, when coupled with strain-sensitive
      nanocomposites, could quantify the strain-induced changes in the dielectric
      property of thin film-coated prosthesis phantoms. The results suggested that ECT
      coupled with embedded thin films could serve as a new noncontact strain sensing
      method for scenarios when tethered strain sensors cannot be used or instrumented,
      especially in the case of osseointegrated prostheses.

PMID- 30205609
TI  - A Co-Polarization Broadband Radar Absorber for RCS Reduction.
AB  - In this article, a single layer co-polarization broadband radar absorber is
      presented. Under normal incidence, it achieves at least 90% of absorption from
      5.6 GHz to 9.1 GHz for both Transverse Electric (TE) and Transverse Magnetic (TM)
      polarizations. Our contribution and the challenge of this work is to achieve
      broadband absorption using a very thin single layer dielectric and it is achieved
      by rotating the resonating element by 45 ? . An original optimized Underlined U
      shape has been developed for the resonating element which provides a broadband co
      polarization absorption. The structure is 12.7 times thinner than the wavelength
      at the center frequency. To understand the absorption mechanism, the transmission
      line model of an absorber and the three near unity absorption peaks at 5.87 GHz,
      7.16 GHz and 8.82 GHz have been used to study the electric and magnetic fields.
      The physical insight of how the three near unity absorption peaks are achieved
      has also been discussed. After fabricating the structure, the measurements were
      found to be in good agreement with the simulation results. Furthermore, with the
      proposed original UUSR resonating element, the operational bandwidth to thickness
      ratio of 6.43 is obtained making the proposed UUSR very competitive.

PMID- 30205611
TI  - The Effect of Crystal Defects on 3D High-Resolution Diffraction Peaks: A FFT
      Based Method.
AB  - Forward modeling of diffraction peaks is a potential way to compare the results
      of theoretical mechanical simulations and experimental X-ray diffraction (XRD)
      data recorded during in situ experiments. As the input data are the strain or
      displacement field within a representative volume of the material containing
      dislocations, a computer-aided efficient and accurate method to generate these
      fields is necessary. With this aim, a current and promising numerical method is
      based on the use of the fast Fourier transform (FFT)-based method. However,
      classic FFT-based methods present some numerical artifacts due to the Gibbs
      phenomenon or "aliasing" and to "voxelization" effects. Here, we propose several
      improvements: first, a consistent discrete Green operator to remove "aliasing"
      effects; and second, a method to minimize the voxelization artifacts generated by
      dislocation loops inclined with respect to the computational grid. Then, we show
      the effect of these improvements on theoretical diffraction peaks.

PMID- 30205613
TI  - Idiopathic Nephrotic Syndrome: Characteristics and Identification of Prognostic
      Factors.
AB  - There are various histopathological forms of idiopathic nephrotic syndrome,
      including minimal change disease (MCD) and focal segmental glomerulosclerosis
      (FSGS). Whereas some relapse predictor factors have been identified in renal
      transplantation, the clinical future of idiopathic nephrotic syndrome in the
      native kidney remains uncertain. We designed a multicentric retrospective
      descriptive cohort study including all patients aged 15 years and over whose
      renal biopsy confirmed MCD or FSGS between January 2007 and December 2014. We
      studied 165 patients with idiopathic nephrotic syndrome; 97 with MCD and 68 with
      FSGS. In the MCD cohort, 91.7% of patients were treated with corticosteroids for
      a median total duration of 13 months. During 45 months of follow-up, 92.8% of
      patients achieved remission and 45.5% experienced relapse. In this cohort, 5% of
      patients experienced terminal kidney disease. With respect to FSGS patients,
      51.5% were treated with corticosteroids for a median total duration of 15 months.
      During 66 months of follow-up, 73.5% of patients achieved remission and 20%
      experienced relapse. In this cohort, 26.5% of patients experienced terminal
      kidney disease. No statistical association was observed between clinical and
      biological initial presentation and relapse occurrence. This study describes the
      characteristics of a cohort of patients with the nephrotic idiopathic syndromes
      of MCD and FSGS from the time of renal biopsy and throughout follow-up.

PMID- 30205612
TI  - Response of Cisplatin Resistant Skov-3 Cells to [Pt(O,O'-Acac)(gamma-Acac)(DMS)]
      Treatment Revealed by a Metabolomic 1H-NMR Study.
AB  - The novel [Pt(O,O'-acac)(gamma-acac)(DMS)], Ptac2S, Pt(II) complex has recently
      gained increasing attention as a potential anticancer agent for its
      pharmacological activity shown in different tumor cell lines, studied both in
      vitro and in vivo. The mechanism of action of Ptac2S, operating on non-genomic
      targets, is known to be very different from that of cis-[PtCl2(NH3)2], cisplatin,
      targeting nucleic acids. In this work, we evaluated the cytotoxicity of Ptac2S on
      the cisplatin resistant Epithelial Ovarian Carcinoma (EOC), SKOV-3 cells, by the
      MTT assay. A 1H-NMR metabolomic approach coupled with multivariate statistical
      analysis was used for the first time for Ptac2S to figure out the biological
      mechanisms of action of the complex. The metabolic variations of intracellular
      metabolites and the composition of the corresponding extracellular culture media
      were compared to those of cisplatin (cells were treated at the IC50 doses of both
      drugs). The reported comparative metabolomic analysis revealed a very different
      metabolic profile between Ptac2S and cisplatin treated samples, thus confirming
      the different mechanism of action of Ptac2S also in the Epithelial Ovarian
      Carcinoma (EOC), SKOV-3 cells line. In particular, higher levels of pyruvate were
      observed in Ptac2S treated, with respect to cisplatin treated, cells (in both
      aqueous and culture media). In addition, a very different lipid expression
      resulted after the exposure to the two drugs (Ptac2S and cisplatin). These
      results suggest a possible explanation for the Ptac2S ability to circumvent
      cisplatin resistance in SKOV-3 cells.

PMID- 30205614
TI  - Molecular Fingerprints of Hemoglobin on a Nanofilm Chip.
AB  - Hemoglobin is an iron carrying protein in erythrocytes and also an essential
      element to transfer oxygen from the lungs to the tissues. Abnormalities in
      hemoglobin concentration are closely correlated with health status and many
      diseases, including thalassemia, anemia, leukemia, heart disease, and excessive
      loss of blood. Particularly in resource-constrained settings existing blood
      analyzers are not readily applicable due to the need for high-level
      instrumentation and skilled personnel, thereby inexpensive, easy-to-use, and
      reliable detection methods are needed. Herein, a molecular fingerprints of
      hemoglobin on a nanofilm chip was obtained for real-time, sensitive, and
      selective hemoglobin detection using a surface plasmon resonance system. Briefly,
      through the photopolymerization technique, a template (hemoglobin) was imprinted
      on a monomeric (acrylamide) nanofilm on-chip using a cross-linker
      (methylenebisacrylamide) and an initiator-activator pair (ammonium persulfate
      tetramethylethylenediamine). The molecularly imprinted nanofilm on-chip was
      characterized by atomic force microscopy and ellipsometry, followed by
      benchmarking detection performance of hemoglobin concentrations from 0.0005 mg mL
      1 to 1.0 mg mL-1. Theoretical calculations and real-time detection implied that
      the molecularly imprinted nanofilm on-chip was able to detect as little as
      0.00035 mg mL-1 of hemoglobin. In addition, the experimental results of
      hemoglobin detection on the chip well-fitted with the Langmuir adsorption
      isotherm model with high correlation coefficient (0.99) and association and
      dissociation coefficients (39.1 mL mg-1 and 0.03 mg mL-1) suggesting a monolayer
      binding characteristic. Assessments on selectivity, reusability and storage
      stability indicated that the presented chip is an alternative approach to current
      hemoglobin-targeted assays in low-resource regions, as well as antibody-based
      detection procedures in the field. In the future, this molecularly imprinted
      nanofilm on-chip can easily be integrated with portable plasmonic detectors,
      improving its access to these regions, as well as it can be tailored to detect
      other proteins and biomarkers.

PMID- 30205615
TI  - Dietary Natural N-Acetyl-d-Glucosamine Prevents Bone Loss in Ovariectomized Rat
      Model of Postmenopausal Osteoporosis.
AB  - Postmenopausal osteoporosis has seriously affected the life quality of elderly
      women. A natural polymer, chitin, obtained from shells of crab and shrimp, has
      been widely used in the biomedical field owing to its nontoxicity,
      biocompatibility, and biodegradability. In this study, natural N-acetyl-d
      glucosamine (NAG) was prepared from liquefied chitin. The protective activities
      of NAG in postmenopausal osteoporosis were evaluated on Sprague Dawley rats and
      osteoblast-based models. Results showed that oral administration of NAG boosted
      trabecular bone volume and trabecular numbers. Additionally, the calcium content
      in the femur and tibia increased, and femoral biomechanical properties improved.
      Furthermore, NAG supplementation significantly lowered alkaline phosphatase
      levels and increased calcium content in the serum of ovariectomized rats. In
      vitro studies showed that NAG markedly promoted cell proliferation and stimulated
      osteoblast differentiation of mouse calvaria origin MC3T3-E1 cells with increased
      alkaline phosphatase activity in a concentration-dependent manner. Moreover, NAG
      effectively protected osteoblasts from oxidative damage induced by hydrogen
      peroxide. In conclusion, our data provide an additional foundation for dietary
      supplementation of NAG, which could protect and reverse osteopenia in
      postmenopausal women.

PMID- 30205616
TI  - Fucoidan Extracted from Undaria pinnatifida: Source for Nutraceuticals/Functional
      Foods.
AB  - The importance of fucoidan as a functional ingredient in food, health products,
      and pharmaceutics is well-recognized due to its beneficial biological effects.
      Fucoidan is usually extracted from brown seaweeds, including Undaria pinnatifida.
      Fucoidan exhibits beneficial bio-activity and has antioxidant, anticancer, and
      anticoagulant properties. This review focuses on the biological activity of U.
      pinnatifida-derived fucoidan and investigates its structure-activity or fraction
      activity relationship. It also describes several fucoidan extracts, along with
      their claimed anticancer effects. It aims to provide information and thoughts for
      future research such as the development of fucoidan into functional foods or
      nutraceuticals.

PMID- 30205610
TI  - Crosstalk of the Brassinosteroid Signalosome with Phytohormonal and Stress
      Signaling Components Maintains a Balance between the Processes of Growth and
      Stress Tolerance.
AB  - Brassinosteroids (BRs) are a class of phytohormones, which regulate various
      processes during plant life cycle. Intensive studies conducted with genetic,
      physiological and molecular approaches allowed identification of various
      components participating in the BR signaling-from the ligand perception, through
      cytoplasmic signal transduction, up to the BR-dependent gene expression, which is
      regulated by transcription factors and chromatin modifying enzymes. The
      identification of new components of the BR signaling is an ongoing process,
      however an emerging view of the BR signalosome indicates that this process is
      interconnected at various stages with other metabolic pathways. The signaling
      crosstalk is mediated by the BR signaling proteins, which function as components
      of the transmembrane BR receptor, by a cytoplasmic kinase playing a role of the
      major negative regulator of the BR signaling, and by the transcription factors,
      which regulate the BR-dependent gene expression and form a complicated regulatory
      system. This molecular network of interdependencies allows a balance in
      homeostasis of various phytohormones to be maintained. Moreover, the components
      of the BR signalosome interact with factors regulating plant reactions to
      environmental cues and stress conditions. This intricate network of interactions
      enables a rapid adaptation of plant metabolism to constantly changing
      environmental conditions.

PMID- 30205619
TI  - Temporal Encoding to Reject Background Signals in a Low Complexity, Photon
      Counting Communication Link.
AB  - Communicating information at the few photon level typically requires some
      complexity in the transmitter or receiver in order to operate in the presence of
      noise. This in turn incurs expense in the necessary spatial volume and power
      consumption of the system. In this work, we present a self-synchronised free
      space optical communications system based on simple, compact and low power
      consumption semiconductor devices. A temporal encoding method, implemented using
      a gallium nitride micro-LED source and a silicon single photon avalanche photo
      detector (SPAD), demonstrates data transmission at rates up to 100 kb/s for 8.25
      pW received power, corresponding to 27 photons per bit. Furthermore, the signals
      can be decoded in the presence of both constant and modulated background noise at
      levels significantly exceeding the signal power. The system's low power
      consumption and modest electronics requirements are demonstrated by employing it
      as a communications channel between two nano-satellite simulator systems.

PMID- 30205617
TI  - The Role of IL-33/ST2 Pathway in Tumorigenesis.
AB  - Cancer is initiated by mutations in critical regulatory genes; however, its
      progression to malignancy is aided by non-neoplastic cells and molecules that
      create a permissive environment known as the tumor stroma or microenvironment
      (TME). Interleukin 33 (IL-33) is a dual function cytokine that also acts as a
      nuclear factor. IL-33 typically resides in the nucleus of the cells where it is
      expressed. However, upon tissue damage, necrosis, or injury, it is quickly
      released into extracellular space where it binds to its cognate receptor
      suppression of tumorigenicity 2 (ST2)L found on the membrane of target cells to
      potently activate a T Helper 2 (Th2) immune response, thus, it is classified as
      an alarmin. While its role in immunity and immune-related disorders has been
      extensively studied, its role in tumorigenesis is only beginning to be elucidated
      and has revealed opposing roles in tumor development. The IL-33/ST2 axis is
      emerging as a potent modulator of the TME. By recruiting a cohort of immune
      cells, it can remodel the TME to promote malignancy or impose tumor regression.
      Here, we review its multiple functions in various cancers to better understand
      its potential as a therapeutic target to block tumor progression or as adjuvant
      therapy to enhance the efficacy of anticancer immunotherapies.

PMID- 30205620
TI  - Translational Medicine in Pulmonary-Renal Crosstalk: Therapeutic Targeting of p
      Cresyl Sulfate Triggered Nonspecific ROS and Chemoattractants in Dyspneic
      Patients with Uremic Lung Injury.
AB  - Molecular mechanisms and pathological features of p-Cresyl sulfate (PCS)-induced
      uremic lung injury (ULI) in chronic kidney disease (CKD) remain unclear. We
      analyzed pleural effusions (PE) from CKD and non-CKD patients for uremic toxins,
      reactive oxygen species (ROS), and chemotactic cytokines. Correlations between PE
      biomarkers and serum creatinine were also studied. Cell viability and
      inflammatory signaling pathways were investigated in PCS-treated human alveolar
      cell model. To mimic human diseases, CKD-ULI mouse model was developed with
      quantitative comparison of immunostaining and morphometric approach. PE from CKD
      patients enhance expressions of uremic toxins, hydroxyl radicals, and IL-5/IL
      6/IL-8/IL-10/IL-13/ENA-78/GRO alpha/MDC/thrombopoietin/VEGF. PE concentrations of
      ENA-78/VEGF/IL-8/MDC/PCS/indoxyl sulphate correlate with serum creatinine
      concentrations. In vitro, PCS promotes alveolar cell death, cPLA2/COX-2/aquaporin
      4 expression, and NADPH oxidase/mitochondria activation-related ROS.
      Intracellular ROS is abrogated by non-specific ROS scavenger N-acetyl cysteine
      (NAC), inhibitors of NADPH oxidase and mitochondria-targeted superoxide
      scavenger. However, only NAC protects against PCS-induced cell death. In vivo,
      expressions of cPLA2/COX2/8-OHdG, resident alveolar macrophages, recruited
      leukocytes, alveolar space, interstitial edema and capillary leakage increase in
      lung tissues of CKD-ULI mice, and NAC pretreatment ameliorates alveolar-capillary
      injury. PCS causes alveolar-capillary injury through triggering intracellular
      ROS, downstream prostaglandin pathways, cell death, and activating leukocytes to
      release multiplex chemoattractants and extracellular ROS. Thus PCS and
      nonspecific ROS serve as potential therapeutic targets.

PMID- 30205621
TI  - Computer-Aided Approach for Rapid Post-Event Visual Evaluation of a Building
      Facade.
AB  - After a disaster strikes an urban area, damage to the facades of a building may
      produce dangerous falling hazards that jeopardize pedestrians and vehicles. Thus,
      building facades must be rapidly inspected to prevent potential loss of life and
      property damage. Harnessing the capacity to use new vision sensors and associated
      sensing platforms, such as unmanned aerial vehicles (UAVs) would expedite this
      process and alleviate spatial and temporal limitations typically associated with
      human-based inspection in high-rise buildings. In this paper, we have developed
      an approach to perform rapid and accurate visual inspection of building facades
      using images collected from UAVs. An orthophoto corresponding to any reasonably
      flat region on the building (e.g., a facade or building side) is automatically
      constructed using a structure-from-motion (SfM) technique, followed by image
      stitching and blending. Based on the geometric relationship between the collected
      images and the constructed orthophoto, high-resolution region-of-interest are
      automatically extracted from the collected images, enabling efficient visual
      inspection. We successfully demonstrate the capabilities of the technique using
      an abandoned building of which a facade has damaged building components (e.g.,
      window panes or external drainage pipes).

PMID- 30205618
TI  - Targeting Amyloid Aggregation: An Overview of Strategies and Mechanisms.
AB  - Amyloids result from the aggregation of a set of diverse proteins, due to either
      specific mutations or promoting intra- or extra-cellular conditions.
      Structurally, they are rich in intermolecular beta-sheets and are the causative
      agents of several diseases, both neurodegenerative and systemic. It is believed
      that the most toxic species are small aggregates, referred to as oligomers,
      rather than the final fibrillar assemblies. Their mechanisms of toxicity are
      mostly mediated by aberrant interactions with the cell membranes, with resulting
      derangement of membrane-related functions. Much effort is being exerted in the
      search for natural antiamyloid agents, and/or in the development of synthetic
      molecules. Actually, it is well documented that the prevention of amyloid
      aggregation results in several cytoprotective effects. Here, we portray the state
      of the art in the field. Several natural compounds are effective antiamyloid
      agents, notably tetracyclines and polyphenols. They are generally non-specific,
      as documented by their partially overlapping mechanisms and the capability to
      interfere with the aggregation of several unrelated proteins. Among rationally
      designed molecules, we mention the prominent examples of beta-breakers peptides,
      whole antibodies and fragments thereof, and the special case of drugs with
      contrasting transthyretin aggregation. In this framework, we stress the pivotal
      role of the computational approaches. When combined with biophysical methods, in
      several cases they have helped clarify in detail the protein/drug modes of
      interaction, which makes it plausible that more effective drugs will be developed
      in the future.

PMID- 30205624
TI  - Ge2Sb2Te5 p-Type Thin-Film Transistors on Flexible Plastic Foil.
AB  - In this work, we show the performance improvement of p-type thin-film transistors
      (TFTs) with Ge 2 Sb 2 Te 5 (GST) semiconductor layers on flexible polyimide
      substrates, achieved by downscaling of the GST thickness. Prior works on GST TFTs
      have typically shown poor current modulation capabilities with ON/OFF ratios <=20
      and non-saturating output characteristics. By reducing the GST thickness to 5 nm,
      we achieve ON/OFF ratios up to ~300 and a channel pinch-off leading to drain
      current saturation. We compare the GST TFTs in their amorphous (as deposited)
      state and in their crystalline (annealed at 200 ? C) state. The highest effective
      field-effect mobility of 6.7 cm 2 /Vs is achieved for 10-nm-thick crystalline GST
      TFTs, which have an ON/OFF ratio of ~16. The highest effective field-effect
      mobility in amorphous GST TFTs is 0.04 cm 2 /Vs, which is obtained in devices
      with a GST thickness of 5 nm. The devices remain fully operational upon bending
      to a radius of 6 mm. Furthermore, we find that the TFTs with amorphous channels
      are more sensitive to bias stress than the ones with crystallized channels. These
      results show that GST semiconductors are compatible with flexible electronics
      technology, where high-performance p-type TFTs are strongly needed for the
      realization of hybrid complementary metal-oxide-semiconductor (CMOS) technology
      in conjunction with popular n-type oxide semiconductor materials.

PMID- 30205622
TI  - Disability and Its Influencing Factors among the Elderly in a County, Guangxi
      Province, China.
AB  - Objectives: This study aims to understand the disability status of the elderly
      residents of a County (Guangxi Province, China) and explore its influencing
      factors. Methods: Respondents consisted of 2300 elderly people aged 60 and above
      from three townships in the county we studied. The Activities of Daily Living
      (ADL) Scale was used to assess the disability of the elderly sample. Chi-square
      test was applied to compare the disability rate among the elderly with different
      demographic characteristics. The graph showed the disability rates of ADL, six
      items of Physical Activities of Daily Living (PADL) and eight items of
      Instrumental Activities of Daily Living (IADL) at different ages. Binary logistic
      regression was used to analyze the influencing factors of disability rate among
      the elderly. Results: The disability rates of ADL, PADL, and IADL in the elderly
      were 43.4%, 11.6%, and 42.4%, respectively. As with the increase in age, the
      disability rates of ADL, IADL, PADL, and their 14 items gradually increased (p <
      0.05), with walking, using the telephone, and using public vehicles having higher
      disability rates than other items. The influencing factors of ADL disability were
      gender (OR = 0.579, 95%CI = 0.441-0.759), age (OR = 2.270, 95%CI = 1.867-2.759;
      OR = 4.719, 95%CI = 2.998-7.429; OR = 6.249, 95%CI = 3.667-10.648), educational
      level (OR = 2.844, 95%CI = 2.076-3.897; OR = 1.677, 95%CI = 1.246-2.230), and
      having metabolic syndrome (MetS) (OR = 1.298, 95%CI = 1.044-1.613). Compared with
      ADL, the influencing factor of PADL disability was gender, whereas that of IADL
      disability was whether someone had MetS. Conclusions: With age, the possibility
      of ADL, PADL, and IADL damage in the elderly is higher. Gender, age, educational
      level, the number of chronic diseases, and whether someone has MetS might be the
      influencing factors of disability. Interventions should be taken from a variety
      of sources specific to the content of each entry.

PMID- 30205625
TI  - Improving GNSS Ambiguity Acceptance Test Performance with the Generalized
      Difference Test Approach.
AB  - In Global navigation satellite system (GNSS) data processing, integer ambiguity
      acceptance test is considered as a challenging problem. A number of ambiguity
      acceptance tests have been proposed from different perspective and then unified
      into the integer aperture estimation (IA) framework. Among all the IA estimators,
      the optimal integer aperture (OIA) achieves the highest success rate with the
      fixed failure rate tolerance. However, the OIA is of less practical appealing due
      to its high computation complexity. On the other hand, the popular discrimination
      tests employ only two integer candidates, which are the essential reason for
      their sub-optimality. In this study, a generalized difference test (GDT) is
      proposed to exploit the benefit of including three or more integer candidates to
      improve their performance from theoretical perspective. The simulation results
      indicate that the third best integer candidates contribute to more than 70%
      success rate improvement for integer bootstrapping success rate higher than 0.8
      case. Therefore, the GDT with three integer candidates (GDT3) achieves a good
      trade-off between the performance and computation burden. The threshold function
      is also applied for rapid determination of the fixed failure rate (FF)-threshold
      for GDT3. The performance improvement of GDT3 is validated with real GNSS data
      set. The numerical results indicate that GDT3 achieves higher empirical success
      rate while the empirical failure rate remains comparable. In a 20 km baseline
      test, the success rate GDT3 increase 7% with almost the same empirical failure
      rate.

PMID- 30205626
TI  - Presence and development of a sensory formation in the eyestalk of the crayfish,
      Astacus leptodactylus (Nordmann, 1842), during its embryonic, larval and adult
      life.
AB  - A sensory papilla is described in the eyestalk of the crayfish Astacus
      leptodactylus during the last embryonic stages and during larval stages by light
      microscopy. This region was also investigated with the scanning electron
      microscopy, which showed sensory hairs in the postmolt adult; they disappear
      during intermolt and premolt. Simultaneous cyclic changes in hair papillae are
      observed in the hypodermis. The possibility of a chemoreceptive function is
      discussed.

PMID- 30205623
TI  - Correlating Synthesis Parameters to Morphological Entities: Predictive Modeling
      of Biopolymer Aerogels.
AB  - In the past decade, biopolymer aerogels have gained significant research
      attention due to their typical properties, such as low density and thermal
      insulation, which are reinforced with excellent biocompatibility,
      biodegradability, and ease of functionalization. Mechanical properties of these
      aerogels play an important role in several applications and should be evaluated
      based on synthesis parameters. To this end, preparation and characterization of
      polysaccharide-based aerogels, such as pectin, cellulose and k-carrageenan, is
      first discussed. An interrelationship between their synthesis parameters and
      morphological entities is established. Such aerogels are usually characterized by
      a cellular morphology, and under compression undergo large deformations.
      Therefore, a nonlinear constitutive model is proposed based on large deflections
      in microcell walls of the aerogel network. Different sizes of the microcells
      within the network are identified via nitrogen desorption isotherms. Damage is
      initiated upon pore collapse, which is shown to result from the failure of the
      microcell wall fibrils. Finally, the model predictions are validated against
      experimental data of pectin, cellulose, and k-carrageenan aerogels. Given the
      micromechanical nature of the model, a clear correlation-qualitative and
      quantitative-between synthesis parameters and the model parameters is also
      substantiated. The proposed model is shown to be useful in tailoring the
      mechanical properties of biopolymer aerogels subject to changes in synthesis
      parameters.

PMID- 30205627
TI  - Structure of the shell and tertiary membranes of eggs of softshell turtles
      (Trionyx spiniferus).
AB  - Eggs of the turtle Trionyx spiniferus are rigid, calcareous spheres averaging 2.5
      cm in diameter. The eggshell is morphologically very similar to avian eggshells.
      The outer crystalline layer is composed of roughly columnar aggregates, or shell
      units, of calcium carbonate in the aragonite form. Each shell unit tapers to a
      somewhat conical tip at its base. Interior to the crystalline layer are two
      tertiary egg membranes: the outer shell membrane and the inner shell membrane.
      The outer shell membrane is firmly attached to the inner surface of the shell,
      and the two membranes are in contact except at the air cell, where the inner
      shell membrane separates from the outer shell membrane. Both membranes are multi
      layered, with the inner shell membrane exhibiting a more fibrous structure than
      the outer shell membrane. Numerous pores are found in the eggshell, and these
      generally occur at the intersection of four or more shell units.

PMID- 30205628
TI  - Sense organs on the antennal flagellum of the mimosa webworm, Homadaula
      anisocentra (Lepidoptera, Glyphipterygidae).
AB  - Five different types of sense organs were found on the antennal flagellum of
      Homadaula anisocentra. These were (1) tactile hairs; (2) thick-walled
      chemoreceptors; (3) thin-walled chemoreceptors of several kinds; (4) styloconic
      chemoreceptors and (5) small chemoreceptor pegs in shallow depressions. No
      coeloconic sense organs were seen.

PMID- 30205629
TI  - Temperature levels and periods of sex determination during incubation of eggs of
      Chelydra serpentina.
AB  - Eggs of Chelydra serpentina were shifted during incubation between the female
      producing temperatures of 20 degrees C or 30 degrees C and the male producing
      temperature of 26 degrees C. In the 20 degrees C and 26 degrees C combination,
      the stages during which incubation temperature determined sex were stage 14
      through stage 16 (stages of normal series, Yntema, '68). In the 30 degrees C and
      26 degrees C combination, the temperature sensitive stages for sex determination
      were stage 14 through stage 19. Incubation at 26 degrees C throughout this period
      was needed to produce all males. Incubation at 30 degrees C during either the
      first or second half of the period produced nearly all females; shorter periods
      of incubation at 30 degrees C were more effective in producing females during the
      second half of the sensitive period. In the 20 degrees C and 26 degrees C
      combination, incubation at 20 degrees C or 26 degrees C for parts of the
      sensitive period produced both males and females. In three of the 57 clutches of
      eggs used in the experiments, incidence of females was atypically high.

PMID- 30205630
TI  - Surface anatomy of branchial food traps of tadpoles: A comparative study.
AB  - Branchial food traps are regions of specialized secretory tissue in the tadpole
      pharynx, where suspended food particles are trapped in mucus. Light and scanning
      electron microscopy were used to study branchial food traps from larvae of ten
      anuran families (36 species). Most anuran larvae from "advanced" (suborder
      Neobatrachia) families (e.g., Hylidae, Ranidae, Bufonidae) have distinct
      secretory pits at the posterior margins of the branchial food traps and secretory
      ridges elsewhere on these surfaces. The apices of columnar PAS-positive,
      secretory cells are exposed on the floors of the secretory pits or in rows at the
      tops of the secretory ridges (secretory zone). Tadpoles from most "archaic"
      (suborder Archaeobatrachia) families (Ascaphidae, Discoglossidae and Pelobatidae)
      either lack secretory pits, or have them poorly defined. They also lack secretory
      ridges but have columnar, mucus-secreting cells whose apices are exposed in a
      seemingly random fashion in the branchial food traps. Rhinophrynus
      (Archaeobatrachia: Rhinophrynidae) has secretory ridges, but the apices of
      secretory cells are not arranged in rows at the tops of the ridges; instead they
      erupt singly or in small clusters on the epithelial surface, in a pattern similar
      to that in Ascaphus, the discoglossids and the pelobatids. It is proposed that
      the generalized condition for the branchial food trap mucosa is one where the
      apices of secretory cells are exposed haphazardly on a flat epithelium and the
      derived condition is one where the surface is organized into ridges. The
      morphology of the branchial food traps in Rhinophrynus suggests that,
      phylogenetically, ridges preceded the coalescing of secretory cell apices into
      distinct rows. Pipidae and Microhylidae have unique patterns in the gross and
      microanatomy of their branchial food traps specific to their families. Branchial
      food trap morphology relates to diets of tadpoles as well as to taxonomy.
      Obligate macrophagous (e.g., carnivorous) tadpoles, irrespective of family, tend
      to have reduced branchial food traps, regularly lack secretory ridges and, in
      extreme cases, lack columnar mucus-secreting cells. Obligate microphagous forms
      (midwater suspension feeding of Xenopus, microhylids and Agalychnis), have
      straight parallel secretory ridges with narrow secretory zones and shallow
      troughs between the ridges. Secretory ridges may help to form mucus strands in
      which food particles are trapped, but they are not essential for planktonic
      entrapment. The hydrodynamic implications of the various topographic patterns
      remain unclear.

PMID- 30205631
TI  - Surface morphology and functions of pharyngeal structures in the larval lamprey
      Petromyzon marinus.
AB  - To gain insight into the multiple functions of a complex biological structure,
      the morphology of the pharynx of the larva (ammocoete) of the lamprey Petromyzon
      marinus was investigated with scanning electron microscopy and histochemistry
      (PAS and Alcian blue). Features studied include the gills, the parabranchial
      chambers external to the gills, intrapharyngeal ciliary tracts, the ridged
      pharyngeal roof, the floor, and the intrapharyngeal taste buds. Significant
      findings are: (1) All (nonciliated) cells lining these structures are covered
      with microvilli or microridges. The pattern and packing density of these membrane
      features vary among different pharyngeal structures. The lumenar membranes of
      pharyngeal lining cells overlie a mucous prosecretion in the apical cytoplasm,
      suggesting that the microvilli/ridges on these membranes function to anchor
      mucus. (2) Patterns of microvilli/ridges on the gill respiratory lamellae differ
      among ammocoetes of different species. (3) Pharyngeal osmo-regulatory cells
      ("chloride cells") could not be identified on the basis of the microvillus/ridge
      pattern. (4) Two types of ciliary tracts are present within the pharynx. One has
      tall (x= 13 MUm) and densely packed cilia, whereas the other has shorter (x= 7
      MUm) and less densely packed ones. Because mucus covers both types of tracts
      their function appears to involve the transport of mucus. (5) Food particles were
      found on the lateral surfaces of the gill filaments and on the surfaces of the
      parabranchial chambers. It appears that goblet cells in the epithelia of these
      regions secrete mucus in which the particles are trapped.

PMID- 30205632
TI  - Studies on the tardigrades. IV. Fine structure of the hindgut of Milnesium
      tardigradum doyere.
AB  - The hindgut of the semi-terrestrial tardigrade, Milnesium tardigradum was
      examined with light and electron microscopy. The hindgut consists of a cloaca and
      an anterior hindgut. It is delineated anteriorly by the pylorus into which four
      Malpighian tubules empty and posteriorly, by a broad cloacal slit. A single
      oviduct enters the hindgut at the junction between the cloaca and the anterior
      hindgut. Two pairs of muscles insert on the cloaca and anterior hindgut
      respectively. Electron microscopic observations demonstrate that the anterior
      hindgut is a specialized transporting epithelium. The luminal surface is covered
      by a thin layer of cuticle which penetrates into channel-like invaginations.
      Numerous mitochondria are concentrated apically. The basal and lateral surfaces
      are also folded. The cells are joined apically by deep tight junctions and a
      simple basal lamina lines the entire hindgut. The cloaca which receives the
      contents of the gut and Malpighian tubules as well as gametes of the reproductive
      tract is a transitional organ that exhibits several characteristics of the
      hypodermis and anterior hindgut. The cuticle of the cloaca changes sequentially
      from the complex structure of the integument to a simple layer of the anterior
      hindgut. The function of the hindgut is discussed with emphasis on the possible
      response of the anterior hindgut to a hypoosmotic habitat, evaporative water loss
      during the induction of anhydrobiosis and low oxygen tension.

PMID- 30205634
TI  - Sense organs on the antennal flagellum of a stonefly (Plecoptera, insecta).
AB  - Tactile hairs, small chemoreceptor pegs, thick-walled chemoreceptors, thin-walled
      chemoreceptors of several types, coeloconic sense organs and campaniform sense
      organs are present on the flagellum of a stonefly, Allocapnia recta (Claassen).

PMID- 30205633
TI  - Structure and carbohydrate histochemistry of the intestine in ten teleostean
      species.
AB  - The morphology and carbohydrate histochemistry of ten teleostean intestines are
      compared. Although there is an absence of regional differentiation seen in higher
      vertebrates, specializations in some species occur in the form of intestinal
      swellings, pyloric ceca and recta, the latter separated by a valve. The
      intestinal lumen is lined by a simple columnar epithelium interspersed with
      goblet cells; multicellular intestinal glands are absent. Thick basement
      membranes seen in centrarchids and Perca flavescens closely resemble the stratum
      compactum found in the lamina propria of esocids. Granular cells, which vary in
      number from species to species, are often seen in the mucosa and submucosa but
      less frequently in the muscularis. In species with intestino-rectal valves, a
      rectum is easily defined by the abrupt appearance of lower mucosal folds, more
      goblet cells and a thicker muscularis. In the remaining species the above
      features appear gradually in the distal intestine. Goblet cells show species
      variations in localization of epithelial mucosubstances, which in broad terms are
      recognized as sulfomucins, sialomucins and neutral mucosubstances. In both
      proximal and distal intestines the majority of goblet cells contain sialomucin
      although small amounts of sulfomucin are also often present. In species without
      intestino-rectal valves, no changes in carbohydrates occur between proximal and
      distal intestines. The possible significance of the heterogeneous character of
      digestive tract mucosubstances is discussed.

PMID- 30205635
TI  - Studies on fish scale formation and resorption. I. Fine structure and
      calcification of the scales in Fundulus heteroclitus (Atheriniformes:
      Cyprinodontidae).
AB  - Fine structure of the scales of Fundulus heteroclitus was examined by scanning
      and transmission electron microscopy. The concentric ridges of the scale surface
      were characterized by the presence of minute, highly calcified, denticles or
      tooth-like processes. Needle-shaped crystals of hydrox-yapatite were precipitated
      not only in the osseous layer but in the intimate lamellae of the fibrillary
      plate except in portions just below the grooves. The calcification of the osseous
      layer was observed to proceed by filling the matrix with patches of crystals. The
      fibrillary plate appeared to calcify by invasion of crystals from the upper
      calcified zone into spaces between collagen fibers.

PMID- 30205636
TI  - Wireless video transmission into the MRI magnet room: implementation and
      evaluation at 1.5T, 3T and 7T.

PMID- 30205637
TI  - A de novo mutation of SMYD1 (p.F272L) is responsible for hypertrophic
      cardiomyopathy in a Chinese patient.

PMID- 30205638
TI  - Using computerized virtual cases to explore diagnostic error in practicing
      physicians.
AB  - Background Diagnostic errors are a significant cause of patient harm. Cognitive
      processes often contribute to diagnostic errors but studying and mitigating the
      effects of these errors is challenging. Computerized virtual patients may provide
      insight into the diagnostic process without the potential for patient harm, but
      the feasibility and utility of using such cases in practicing physicians has not
      been well described. Methods We developed a series of computerized virtual cases
      depicting common presentations of disease that included contextual factors that
      could result in diagnostic error. Cases were piloted by practicing physicians in
      two phases and participant impressions of the case platform and cases were
      recorded, as was outcome data on physician performance. Results Participants
      noted significant challenges in using the case platform. Participants
      specifically struggled with becoming familiar with the platform and adjusting to
      the non-adaptive and constraining processes of the model. Although participants
      found the cases to be typical presentations of problems commonly encountered in
      practice, the correct diagnosis was identified in less than 33% of cases.
      Conclusions The development of virtual patient cases for use by practicing
      physicians requires substantial resources and platforms that account for the non
      linear and adaptive nature of reasoning in experienced clinicians. Platforms that
      are without such characteristics may negatively affect diagnostic performance.
      The novelty of such platforms may also have the potential to increase cognitive
      load. Nonetheless, virtual cases may have the potential to be a safe and robust
      means of studying clinical reasoning performance.

PMID- 30205639
TI  - The Choosing Wisely initiative and laboratory test stewardship.

PMID- 30205640
TI  - Capturing diagnostic errors in incident reporting systems: value of a specific
      "DX Tile" for diagnosis-related concerns.

PMID- 30205641
TI  - Cross-sectional correlates of nesfatin and lipopolysaccharide binding protein in
      metabolic syndrome patients with and without prediabetes.

PMID- 30205642
TI  - The effectiveness of group hope therapy on the mental health of type II diabetic
      patients referred to the diabetes clinic in South East Iran.

PMID- 30205643
TI  - High incidence of concussion, but low knowledge levels among young adults.

PMID- 30205644
TI  - What does social media have to do with health? A case study of Bangkok youths.

PMID- 30205645
TI  - Proline supplementation mitigates the early stage of liver injury in bile duct
      ligated rats.

PMID- 30205646
TI  - BioModelKit - An Integrative Framework for Multi-Scale Biomodel-Engineering.
AB  - While high-throughput technology, advanced techniques in biochemistry and
      molecular biology have become increasingly powerful, the coherent interpretation
      of experimental results in an integrative context is still a challenge.
      BioModelKit (BMK) approaches this challenge by offering an integrative and
      versatile framework for biomodel-engineering based on a modular modelling concept
      with the purpose: (i) to represent knowledge about molecular mechanisms by
      consistent executable sub-models (modules) given as Petri nets equipped with
      defined interfaces facilitating their reuse and recombination; (ii) to compose
      complex and integrative models from an ad hoc chosen set of modules including
      different omic and abstraction levels with the option to integrate spatial
      aspects; (iii) to promote the construction of alternative models by either the
      exchange of competing module versions or the algorithmic mutation of the composed
      model; and (iv) to offer concepts for (omic) data integration and integration of
      existing resources, and thus facilitate their reuse. BMK is accessible through a
      public web interface (www.biomodelkit.org), where users can interact with the
      modules stored in a database, and make use of the model composition features. BMK
      facilitates and encourages multi-scale model-driven predictions and hypotheses
      supporting experimental research in a multilateral exchange.

PMID- 30205647
TI  - First trimester prediction of gestational diabetes mellitus using plasma
      biomarkers: a case-control study.

PMID- 30205648
TI  - Plastic waste as a significant threat to environment - a systematic literature
      review.

PMID- 30205649
TI  - Review of built and natural environment stressors impacting American
      Indian/Alaska-Native children.
AB  - Children's exposures to chemical and non-chemical stressors from their everyday
      environment affects their overall health and well-being. American-Indian/Alaska
      Native (AI/AN) children may have a disproportionate burden of stressors from
      their built and natural environments when compared to children from other
      races/ethnicities. Our objectives were to identify chemical and non-chemical
      stressors from AI/AN children's built and natural environments and evaluate their
      linkages with health and well-being outcomes from the peer reviewed literature.
      Library databases (e.g. PubMed) were searched to identify studies focused on
      these stressors. References were excluded if they: did not discuss AI/AN children
      or they were not the primary cohort; discussed tribes outside the United States
      (U.S.); were reviews or intervention studies; or did not discuss stressors from
      the built/natural environments. Out of 2539 references, 35 remained. Sample
      populations were predominantly (70%) in New York (NY) and Alaska (AK); 14 studies
      reported on the same cohort. Studies with matching stressors and outcomes were
      few, ruling out a quantitative review. Respiratory and developmental outcomes
      were the main outcomes evaluated. Primary non-chemical stressors were residential
      proximity to polluted landscapes, lack of indoor plumbing, and indoor use of wood
      for heating or cooking. The main chemical stressors were volatile organic
      compounds (VOCs), particulate matter (PM2.5), polychlorinated biphenyls (PCBs),
      p,p'-DDE, hexachlorobenzene (HCB), lead, and mercury. Our qualitative review was
      suggestive of a potential increase in respiratory illness from indoor wood use or
      no plumbing, which can be used as a guide to promote healthy environments for
      AI/AN children. We identified limited studies (<40), demonstrating this
      population as understudied. Future studies need to consider: sample populations
      from other tribes in the U.S., stressors outside the household, other elements of
      the natural environment, and an evaluation of stressors from AI/AN children's
      total environment (built, natural, and social).

PMID- 30205650
TI  - Nanostructures: between natural environment and medical practice.

PMID- 30205651
TI  - Progress in research on the role of Omi/HtrA2 in neurological diseases.

PMID- 30205652
TI  - Effects of stress on the auditory system: an approach to study a common origin
      for mood disorders and dementia.

PMID- 30205653
TI  - Cause-specific mortality of patients with severe chronic pain referred to a
      multidisciplinary pain clinic: a cohort register-linkage study.

PMID- 30205654
TI  - Benzimidazole - Schiff bases and their complexes: synthesis, anticancer activity
      and molecular modeling as Aurora kinase inhibitor.
AB  - A new series of Schiff bases containing benzimidazole moiety 11-17 were
      synthesized by the reaction of 4-(1H-benzo[d]imidazol-2-yl)aniline (1) with
      different aromatic aldehydes (4-10) via conventional heating and microwave
      irradiation methods. The structures of the novel Schiff bases were characterized
      by using different spectral data. Also, metal complexes 18-21 of compound 13 were
      synthesized, and their structure was confirmed by spectral measurements (IR, NMR,
      UV), molar conductivity, magnetic susceptibility and thermo-gravimetric analysis.
      The novel synthesized ligand 13 and its complexes 18-21 were tested for their in
      vitro antitumor activities towards breast, liver and lung cancer cell lines.
      Also, the acute toxicity of the prepared compounds 13 and 18-21 was determined in
      vivo. The results showed that the newly synthesized compounds 13 and 18-21
      exhibited a significant activity against cancer, especially for complex 21,
      compared to standard drug doxorubicin. The molecular docking of complexes 20 and
      21 has been also studied as Aurora kinase inhibitors.

PMID- 30205655
TI  - Xanthogranuloma of the sellar region accompanied by growth hormone deficiency:
      case report and literature review.
AB  - Background Xanthogranuloma of the sellar region is a rare entity. Its pathology
      is controversial and it is difficult to strictly differentiate it from
      craniopharyngioma or Rathke's cyst. Case presentation We report a case of
      xanthogranuloma accompanied by growth hormone deficiency in an 11-year-old girl.
      She did not show any other pituitary hormone deficiency or neurological symptoms
      before operation. The preoperative diagnosis was craniopharyngioma, but
      histological findings showed small areas of epithelium. Thus, the final diagnosis
      was xanthogranuloma. Xanthogranuloma is an important cause of growth delay. We
      reviewed 16 cases reported after 2000, and included our case, of xanthogranuloma
      in children. Conclusions Endocrinological symptoms are often regarded as one of
      the few apparent symptoms in xanthogranuloma compared with craniopharyngioma.
      Therefore, we should follow up carefully and accumulate cases.

PMID- 30205656
TI  - Antenatal and prepregnancy care - prevention of perinatal morbidity and
      mortality.

PMID- 30205657
TI  - Reply to comments from Ulf Kongsgaard to our study.

PMID- 30205659
TI  - Mechanisms of change of traditional mindfulness practice in Thai adolescent
      students: a cross-sectional mediation study.

PMID- 30205658
TI  - Comparison of performing 12 weeks' resistance training before, after and/or in
      between aerobic exercise on the hormonal status of aged women: a randomized
      controlled trial.
AB  - Background Physiological aging can now be considered as a multi-factorial process
      that is associated with anatomical and signaling changes associated with
      endocrine function. The purpose of this study was to investigate the comparison
      of performing 12 weeks' resistance training before, after and/or in between
      aerobic exercise on the hormonal status of aged women. Materials and methods
      Forty healthy aged women (age: 67.35 +/- 1.40 years) were randomly divided into
      three training groups and a control group: resistance followed by endurance
      training (ER, n = 12), endurance training followed by resistance training (RE, n
      = 12, interval resistance-endurance (RE) training (INT, n = 12) and a control
      (Con, n = 12) groups. The training program was done over 12 weeks, 3 times per
      week. Endurance training was performed on a cycle ergometer (intensity: 60-90%
      maximum heart rate) and resistance training involved selected resistance
      exercises (intensity: 40-75 one-repetition maximum, 8-18 repeats). All
      participants were evaluated before and after the training period. Results and
      conclusion The data showed that performing resistance training before, after
      and/or in between aerobic exercise did not influence the adaptive response of
      insulin like growth factor-1 (IGF-1) (p = 0.07), growth hormone (p = 0.35),
      cortisol (p = 0.20), insulin (p = 0.72), epinephrine (p = 0.83) and
      norepinephrine (p = 0.86) levels throughout the study. However, when comparing
      pre and post, no significant differences were shown following combined training
      within the SE, ES and INT groups for all variables (p < 0.05), except of IGF-1
      within ES (p = 0.04) and SE (p = 0.02), and testosterone within ES (p = 0.007).
      In conclusion, combined training with RE order may be more effective than other
      orders for increasing anabolic status in aged women.

PMID- 30205660
TI  - Many hours of watching medical TV shows is associated with greater medical
      knowledge.

PMID- 30205661
TI  - Awareness of bicycle light use of young adults.

PMID- 30205662
TI  - A variable selection approach in the multivariate linear model: an application to
      LC-MS metabolomics data.
AB  - Omic data are characterized by the presence of strong dependence structures that
      result either from data acquisition or from some underlying biological processes.
      Applying statistical procedures that do not adjust the variable selection step to
      the dependence pattern may result in a loss of power and the selection of
      spurious variables. The goal of this paper is to propose a variable selection
      procedure within the multivariate linear model framework that accounts for the
      dependence between the multiple responses. We shall focus on a specific type of
      dependence which consists in assuming that the responses of a given individual
      can be modelled as a time series. We propose a novel Lasso-based approach within
      the framework of the multivariate linear model taking into account the dependence
      structure by using different types of stationary processes covariance structures
      for the random error matrix. Our numerical experiments show that including the
      estimation of the covariance matrix of the random error matrix in the Lasso
      criterion dramatically improves the variable selection performance. Our approach
      is successfully applied to an untargeted LC-MS (Liquid Chromatography-Mass
      Spectrometry) data set made of African copals samples. Our methodology is
      implemented in the R package MultiVarSel which is available from the
      Comprehensive R Archive Network (CRAN).

PMID- 30205663
TI  - Body image is more negative in patients with chronic low back pain than in
      patients with subacute low back pain and healthy controls.

PMID- 30205664
TI  - Erratum to: A comparative proteomic analysis for adventitious root formation in
      lotus root (Nelumbo nucifera Gaertn).

PMID- 30205665
TI  - Erratum to: Transcriptome profiling reveals an IAA-regulated response to
      adventitious root formation in lotus seedling.

PMID- 30205666
TI  - Manuscript a novel use for the precordial Doppler to verify central venous
      access.

PMID- 30205667
TI  - A prospective randomised controlled double-blind study to compare between
      auscultation and lung ultrasonography to assess position of double lumen tube in
      elective thoracic surgeries involving one lung ventilation at tertiary care
      cancer institute.
AB  - Background: With ability of lung ultrasound (LUS) to identify regional lung
      ventilation and collapse, we hypothesize that LUS can be a better method than
      auscultation to assess lung isolation in determination of position of double
      lumen tube (DLT). Methods: A randomized controlled study was conducted in cancer
      institute from November 2014 to December 2015, in hundred adult patients
      undergoing elective thoracic surgeries. Patients with tracheostomy, difficult
      airway and pleural-based pathologies were excluded. After anesthesia induction
      and DLT insertion, patients were randomized into group A (auscultation) and group
      B (LUS). Experienced anesthesiologists assessed regional ventilation by
      respective method as per randomization. Final confirmation of position of DLT was
      done by a blinded anesthesiologist using bronchoscope. Contingency tables were
      plotted to know sensitivity, specificity, positive predictive value (PPV),
      negative predictive value (NPV), and accuracy for each method. Results: Data of
      91 patients was analysed (group A - 47, group B - 44, 9 patients did not receive
      allocated intervention). As compared with auscultation, LUS had significantly
      higher sensitivity (94.1% vs. 73.3%, P = 0.010), PPV (57.1% vs. 35.5%, P =
      0.044), NPV (93.8% vs. 75.0%, P = 0.018) and accuracy (70.5% vs. 48.9%, P =
      0.036) for assessment of position of DLT. Differences in specificity (55.6% vs.
      37.5%, P = 0.101), and area under receiver operating curve (0.748; 95% CI: 0.604
      0.893 vs 0.554, 95% CI: 0.379-0.730; P = 0.109) were not significant.
      Conclusions: LUS, as compared to auscultation, is a superior method in assessment
      of lung isolation for determining position of DLT.

PMID- 30205668
TI  - Syndecan-2 Methylation as a New Biomarker for Early Detection of Colorectal
      Neoplasm.

PMID- 30205669
TI  - Factors Predictive of Malignancy Potency in Pure Branch Duct Intraductal
      Papillary Mucinous Neoplasm of the Pancreas without Mural Nodules.

PMID- 30205671
TI  - Gender-Specific Associations of Sensory Impairments with Depression and Cognitive
      Impairment in Later Life.
AB  - OBJECTIVE: Sensory impairments, such as vision and hearing impairments, increase
      with age, and studies have shown that self-reported vision and hearing
      impairments are associated with adverse mental health outcomes in later life.
      Although gender differences may exist in the associations between sensory
      impairments and geriatric mental health outcomes, little research has been done
      examining gender differences in the above associations. Therefore, the purpose of
      this study was to investigate the relationship between self-reported sensory
      impairments and geriatric mental health outcomes with the aim of determining
      whether any association differs by gender. METHODS: The study sample was drawn
      from a nationally representative data set, the 2012 Korean Longitudinal Study of
      Ageing, and the final sample consisted of 2,167 females and 1,664 males aged 65
      and over. Self-reported sensory impairments were categorized into four groups: no
      sensory impairment (reference), vision impairment only, hearing impairment only,
      and dual sensory impairment. Depression and cognitive impairment were used as
      dependent variables in separate analyses. RESULTS: Adjusted for confounding
      variables, results from a multivariate analysis showed that vision impairment was
      significantly associated with depression only among women. Moreover, hearing
      impairment was significantly associated with cognitive impairment for women, but
      not for men. Having dual sensory impairment was associated with depression only
      among men, while having dual sensory impairment was associated with cognitive
      impairment only among women. CONCLUSION: These findings suggest that the
      associations between sensory impairments and geriatric mental health outcomes
      vary according to gender. Therefore, gender-specific strategies in healthcare
      policies are needed.

PMID- 30205672
TI  - Genistein Improves the Major Depression through Suppressing the Expression of miR
      221/222 by Targeting Connexin 43.
AB  - OBJECTIVE: Recent studies have indicated the possibility that genistein may
      improve depression via regulating the expression of miR221/222. This study is to
      explore whether genistein could improve depression by altering miR-221/222 levels
      and investigate the possible mechanisms involved in the improvement effect of
      genistein. METHODS: The animal model of depression was established through
      unpredictable chronic mild stress. Nest building test and splash test were
      adapted to evaluate the effects of genistein on depressive symptoms in mice. qRT
      PCR and western blot analysis were used to detect the expression of miR-221/222
      and connexin 43 (Cx43) in the prefrontal cortex of the mice. In vitro, U87-MG
      astrocytes were treated with genistein and the expression of miR-221/222 and Cx43
      was measured. The dual-luciferase reporter assay was used to verify whether Cx43
      was a direct target of miR-221/222. RESULTS: The behavioral tests showed that
      genistein could significantly reduce depression symptoms of mice, and this
      remission was not affected by gender. Genistein in vivo and in vitro could reduce
      increased levels of miR-221 and miR-222 in the prefrontal cortex of depressed
      mice, while upregulate Cx43 expression. Dual-luciferase reporter assay suggested
      Cx43 was directly regulated by miR-221/222 in astrocytes. CONCLUSION: Genistein
      can play its antidepressant effect through down-regulating miR-221/222 by
      targeting Cx43.

PMID- 30205670
TI  - Relationship between Autistic Spectrum Trait and Regional Cerebral Blood Flow in
      Healthy Male Subjects.
AB  - OBJECTIVE: Autistic spectrum traits are postulated to lie on a continuum that
      extends between individuals with autism and individuals with typical development.
      The present study was carried out to investigate functional and network
      abnormalities associated with autistic spectrum trait in healthy male subjects.
      METHODS: Subjects were 41 healthy male subjects who underwent the social
      responsiveness scale-adult (SRS-A) and magnetic resonance imaging. RESULTS: There
      was significant positive correlation between the total score of SRS-A and the
      regional cerebral blood flow (CBF) in posterior cingulate cortex (PCC). Also,
      there were changes in functional network such as in cingulate corti, insula and
      fusiform cortex. Further, we also found the significant difference of functional
      networks between the healthy male subjects with high or low autistic spectrum
      trait, and these points were congruent with the previous perceptions derived from
      autistic-spectrum disorders. CONCLUSION: These findings suggest a biological
      basis for the autistic spectrum trait and may be useful for the imaging marker of
      autism symptomatology.

PMID- 30205673
TI  - Zwitterionic Inorganic Benzene Valence Isomer with sigma-Bonding between Two pi
      Orbitals.
AB  - Despite the large number of plausible isomers of benzene (C6H6), only four
      valence isomers [(CH)6] have been experimentally detected, all of which are
      nonionic and possess skeletal frameworks built from localized C-C bonds. Herein,
      we present the isolation of a diazatetraborabenzene analogue of a hypothetical
      zwitterionic valence isomer of benzene. Therein, two electrons are delocalized
      over the four boron atoms in the six-membered B4N2 ring, which is a result of the
      sigma-bonding interaction between two odd-electron B-B pi-orbitals. Simple
      treatment with a crown ether leads to the formation of a paramagnetic potassium
      doped radical ion pair that exhibits a thermally populated triplet character.

PMID- 30205675
TI  - Acceptorless Dehydrogenative Coupling Using Ammonia: Direct Synthesis of N
      Heteroaromatics from Diols Catalyzed by Ruthenium.
AB  - The synthesis of N-heteroaromatic compounds via an acceptorless dehydrogenative
      coupling process involving direct use of ammonia as the nitrogen source was
      explored. We report the synthesis of pyrazine derivatives from 1,2-diols and the
      synthesis of N-substituted pyrroles by a multicomponent dehydrogenative coupling
      of 1,4-diols and primary alcohols with ammonia. The acridine-based Ru-pincer
      complex 1 is an effective catalyst for these transformations, in which the
      acridine backbone is converted to an anionic dearomatized PNP-pincer ligand
      framework.

PMID- 30205674
TI  - Pt-Embedded CuO x-CeO2 Multicore-Shell Composites: Interfacial Redox Reaction
      Directed Synthesis and Composition-Dependent Performance for CO Oxidation.
AB  - Exploring the state-of-the-art heterogeneous catalysts has been a general concern
      for sustainable and clean energy. Here, Pt-embedded CuO x-CeO2 multicore-shell
      (Pt/CuO x-CeO2 MS) composites are fabricated at room temperature via a one-pot
      and template-free procedure for catalyzing CO oxidation, a classical probe
      reaction, showing a volcano-shaped relationship between the composition and
      catalytic activity. We experimentally unravel that the Pt/CuO x-CeO2 MS
      composites are derived from an interfacial autoredox process, where Pt
      nanoparticles (NPs) are in situ encapsulated by self-assembled ceria nanospheres
      with CuO x clusters adhered through deposition/precipitation-calcination process.
      Only Cu-O and Pt-Pt coordination structures are determined for CuO x clusters and
      Pt NPs in Pt/CuO x-CeO2 MS, respectively. Importantly, the close vicinity between
      Pt and CeO2 benefits to more oxygen vacancies in CeO2 counterparts and results in
      thin oxide layers on Pt NPs. Meanwhile, the introduction of CuO x clusters is
      crucial for triggering synergistic catalysis, which leads to high resistance to
      aggregation of Pt NPs and improvement of catalytic performance. In CO oxidation
      reaction, both Ptdelta+-CO and Cu+-CO can act as active sites during CO
      adsorption and activation. Nonetheless, redundant content of Pt or Cu will induce
      a strongly bound Pt-O-Ce or Cu-[O x]-Ce structures in air-calcinated Pt/CuO x
      CeO2 MS composites, respectively, which are both deleterious to catalytic
      reactivity. As a result, the composition-dependent catalytic activity and
      superior durability of Pt/CuO x-CeO2 MS composites toward CO oxidation reaction
      are achieved. This work should be instructive for fabricating desirable
      multicomponent catalysts composed of noble metal and bimetallic oxide composites
      for diverse heterogeneous catalysis.

PMID- 30205676
TI  - Predicting Thermodynamic Properties of Alkanes by High-Throughput Force Field
      Simulation and Machine Learning.
AB  - Knowledge of the thermodynamic properties of molecules is essential for chemical
      process design and the development of new materials. Experimental measurements
      are often expensive and not environmentally friendly. In the past, studies using
      molecular simulations have focused on a specific class of molecules, owing to the
      lack of a consistent force field and simulation protocol. To solve this problem,
      we have developed a high-throughput force field simulation (HT-FFS) procedure by
      combining a recently developed general force field with a validated simulation
      protocol to calculate thermodynamic properties for large number of molecules.
      This procedure is applied to calculate liquid densities, heats of vaporization,
      heat capacities, vapor-liquid equilibrium curves, critical temperatures, critical
      densities and surface tensions for a wide range of alkanes. The predictions agree
      well with available experimental data in terms of accuracy and precision,
      demonstrating that HT-FFS is a valid approach to supplementing experimental
      measurements. Furthermore, the large amount of data generated by HT-FFS lays a
      foundation for machine learning. We have developed an artificial neural network
      that demonstrates the feasibility of expanding predictions beyond simulation
      using a machine learning model.

PMID- 30205677
TI  - Protein Dielectrophoresis in Solution.
AB  - Proteins experience either pulling or repelling force from the gradient of an
      external electric field due to the effect known as dielectrophoresis (DEP). The
      susceptibility to the field gradient is traditionally calculated from the
      solution of the electrostatic boundary-value problem, which requires assigning a
      dielectric constant to the protein. This assignment is essential since the DEP
      susceptibility is proportional, in dielectric theories, to the Clausius-Mossotti
      factor, the sign of which is controlled by whether the protein dielectric
      constant is below (repelling) or above (pulling) the dielectric constant of
      water. The dielectric constant is not uniquely or even well-defined for a
      particle of molecular size and the Clausius-Mossotti factor is shown here to be
      inadequate for describing the dipolar response of the protein and hydration
      water. An alternative theory is developed from the standpoint of molecular
      properties of the protein solute and water solvent. The effective polarity of the
      protein molecule enters the theory in terms of the variance of its molecular
      dipole moment and its refractive index. Molecular dynamics (MD) simulations of
      the protein cytochrome c in solution are performed to calculate the dipolar
      susceptibilities entering the theory. We find that tumbling of the protein on the
      nanosecond time scale results in a positive DEP (pulling). The DEP susceptibility
      for cytochrome c acquired from MD simulations is 103-104 times higher than
      predicted by the Clausius-Mossotti factor. Nevertheless, this high DEP
      susceptibility is fully consistent with empirically confirmed Oncley's equation
      connecting the protein dipole to dielectric increments of protein solutions. For
      cytochrome c, high DEP susceptibilities calculated from MD are consistent with
      experimental dielectric data. We provide a general relation connecting the DEP
      susceptibility to the dielectric increment of solution.

PMID- 30205678
TI  - Effects of Transgenic Bt Rice Containing the Cry1Ab Protein on the
      Gastrointestinal Health of Highly Inbred Wuzhishan Pigs after Two Generations of
      Feeding.
AB  - To assess the safety of transgenic Bt rice, we evaluated the chronic effects of
      Bt rice carrying the Cry1Ab protein (1.64 mg/kg) on the gut microbiota and
      histopathology in highly inbred Wuzhishan pigs (WZSP) in a two-generation feeding
      study. The WZSP of the f0 ( n = 26) and f1 ( n = 27) generations were divided
      into GM and Non-GM groups and fed for 360 and 420 days with Bt and isogenic
      parent-line rice, respectively. The high-throughput 16S rRNA gene sequencing
      results revealed that the relative abundance of the family Enterobacteriaceae and
      genus Escherichia were significantly different between f1F and f1Z. The level of
      the genera CF231 and SMB53 in the f0Z group was higher than that in the f0F
      group. In addition, no abnormal histopathology changes in the main
      gastrointestinal tissues were found after feeding with Bt rice. In conclusion, Bt
      rice consumption has no adverse effects on the gut microbiota or organ function
      of WZSP.

PMID- 30205679
TI  - Mesoscopic Structure Facilitates Rapid CO2 Transport and Reactivity in CO2
      Capture Solvents.
AB  - Mass transfer coefficients of CO2 are anomalously high in water-lean solvents as
      compared to aqueous amines. Such phenomena are intrinsic to the molecular and
      nanoscale structure of concentrated organic CO2 capture solvents. To decipher the
      connections, we performed in situ liquid time-of-flight secondary ionization mass
      spectroscopy on a representative water-lean solvent, 1-((1,3-Dimethylimidazolidin
      2-ylidene)amino)propan-2-ol (IPADM-2-BOL). Two-dimensional (2D) and three
      dimensional (3D) chemical mapping of the solvent revealed that IPADM-2-BOL
      exhibited a heterogeneous molecular structure with regions of CO2-free solvent
      coexisting with clusters of zwitterionic carbonate ions. Chemical mapping were
      consistent with molecular dynamic simulation results, indicating CO2 diffusing
      through pockets and channels of unreacted solvent. The observed mesoscopic
      structure promotes and enhances the diffusion and reactivity of CO2, likely
      prevalent in other water-lean solvents. This finding suggests that if the size,
      shape and orientation of the domains can be controlled, more efficient CO2
      capture solvents could be developed to enhance mass-transfer and uptake kinetics.

PMID- 30205680
TI  - Comprehensive Metabolomics Analysis of Mandarins ( Citrus reticulata) as a Tool
      for Variety, Rootstock, and Grove Discrimination.
AB  - The metabolite profile responsible for the quality of mandarin fruit is
      influenced by preharvest factors including genotype, rootstock, grove location,
      etc. In this paper, mandarin varieties were discriminated using metabolomics.
      Additionally, effects on metabolic profiles due to grove location and rootstock
      differences were also investigated. Results revealed that mandarin varieties
      could be differentiated using the metabolite profile, while the compositions of
      flavonoids have the potential for variety differentiation. With regard to fruits
      of the same variety, grove location might determine the overall profile of
      metabolites, whereas rootstock possibly affected composition of secondary
      metabolites. Pathway enrichment analysis demonstrated that biosynthesis pathways
      of terpenoids and steroids involving limonene and linalool were highly influenced
      by variety diversity. Moreover, the flavonoid biosynthesis pathway, involving
      hesperetin, naringenin, eriodictyol, and taxifolin, was indicated to have a close
      relationship with rootstock differentiation. This study provides useful and
      important information with depth for breeding and optimizing preharvest
      practices.

PMID- 30205681
TI  - Design of Tumor Microenvironment-Responsive Drug-Drug Micelle for Cancer
      Radiochemotherapy.
AB  - Concomitant radiochemotherapy is a major therapeutic strategy for treating
      malignant tumors. However, the greatest challenge is how to improve the
      therapeutic effect of radiochemotherapy to achieve the proper synergetic chemo
      /radiotherapy for the tumor. In this study, ferrocenium (antitumor effect) and
      nitroimidazole (hypoxic cell radiosensitization) conjugates were synthesized to
      form amphiphilic ferrocenium-hexane-nitroimidazole (Fe-NI), which can self
      assemble in aqueous solution. The Fe-NI micelles successfully encapsulate the
      hydrophobic chemotherapy drug doxorubicin (DOX) and are modified with hyaluronic
      acid (HA) by electrostatic interactions to form HA-Fe-NIs-DOX micelles. HA-Fe-NIs
      DOX micelles rapidly release DOX under tumor hypoxia and a high glutathione (GSH)
      environment and achieve a synergetic chemo-/radiotherapy for the tumor based on
      the properties of nitroimidazoles and ferrocenes. The biodistribution results
      obtained in vivo reveal an effective accumulation in the tumor. The HA-Fe-NIs-DOX
      micelles show a significant radiosensitizing effect on the tumors, and the
      combination of chemotherapy and radiotherapy is realized for the treatment of
      tumor in vitro and in vivo. These findings illustrate that HA-Fe-NIs micelles are
      a promising candidate, which enhances the antitumor effects as a DOX delivery
      system, owing to the synergistic mechanisms of antitumor agents and chemo
      /radiotherapy.

PMID- 30205682
TI  - Hierarchical Nanosheet-Built CoNi2S4 Nanotubes Coupled with Carbon-Encapsulated
      Carbon Nanotubes@Fe2O3 Composites toward High-Performance Aqueous Hybrid
      Supercapacitor Devices.
AB  - A hybrid supercapacitor system was designed with ternary Ni-Co sulfides (CoNi2S4)
      as cathode materials and Fe-based composites [carbon nanotubes (CNTs)@Fe2O3@C] as
      anode materials to achieve excellent overall electrochemical performance with
      high energy and power density as well as long lifespan. Here, hierarchical
      CoNi2S4 nanotubes were synthesized by a solvothermal route followed by
      sulfidation reaction for the first time, in which nanotubes were composed of
      interconnected ultrathin nanosheets. Consequently, such a unique nanosheet-built
      nanoarchitecture enables the CoNi2S4 cathode with multidimensional synergistic
      effect from one-dimensional nanotubes, two-dimensional nanosheets, and three
      dimensional frameworks. Profiting from its structural merits, the as-prepared
      CoNi2S4 nanotubes deliver a high capacitance of 2552 F g-1 at 1 A g-1 with a high
      rate capacity of 81% at 25 A g-1. In addition, the CNTs@Fe2O3@C anode materials
      incorporating carbon-encapsulated ultrafine Fe2O3 nanoparticles into CNT matrices
      were achieved by atomic layer deposition and acetylene thermal decomposition,
      which realize excellent electrochemical properties (678 F g-1 at 1 A g-1 and
      capacity retention of 82% at 25 A g-1) that matched well with CoNi2S4 cathode
      materials. With the well-designed nanostructure and matching of materials and
      properties, the corresponding aqueous hybrid device exhibits a wide output
      voltage window of 0-1.75 V with a maximum energy density of 90.5 W h kg-1 at a
      power density of 1.84 kW kg-1. Meanwhile, a high energy density of 73.1 W h kg-1
      can be retained at an ultrahigh power density of 26.9 kW kg-1. Moreover, the
      hybrid device has a stable cycling ability with 82.1% retention over 5000 cycles.
      This coordinative design strategy integrating the cathode and anode electrodes
      developed in this work provides a novel way to manufacture next-generation energy
      storage device with high performance and safety.

PMID- 30205684
TI  - Regression Modelability Index: A New Index for Prediction of the Modelability of
      Data Sets in the Development of QSAR Regression Models.
AB  - Prediction of the capability of a data set to be modeled by a statistical
      algorithm in the development of quantitative structure-activity relationship
      (QSAR) regression models is an important issue that allows researchers to avoid
      unnecessary tasks, wasted time, and/or the need to depurate the molecule
      composition of the data set in order to achieve an improvement of the model's
      accuracy. In this paper, we propose and formulate a new index that correlates
      with the performance of QSAR models. This index, the regression modelability
      index, requires very low computational cost and is based on the rivality between
      the nearest neighbors of the molecules in the data set. This rivality allows
      measurement of the capability of each molecule of the data set to be correctly
      predicted by a regression algorithm. In this study, using 40 data sets with very
      different characteristics regarding the number of molecules and activity values,
      we prove the high correlation between the proposed regression modelability index
      and the correlation coefficient in cross-validation ( Q2), reaching r2 values of
      0.8. In addition, we describe the ability of this index to discover the outliers
      detected by the regression algorithms, allowing easy data set depuration in the
      first stages of the construction of QSAR regression models.

PMID- 30205683
TI  - Sensitive Screening Method for Determination of Pyrethroids in Chicken Eggs and
      Various Meat Samples by Gas Chromatography and Electron Capture Detection.
AB  - A sensitive and reproducible screening analytical method is described for the
      determination of six pyrethroids (phenothrin, permethrin, cyfluthrin,
      cypermethrin, deltamethrin, fenvalerate) in egg and meat samples by gas
      chromatography and electron capture detection (GC-ECD). A fast cleanup procedure,
      based on solid-phase extraction has been used, ensuring reduced solvent
      consumption and time and allowing the simultaneous preparation of multiple sample
      extracts. Under the optimal chromatographic conditions, an efficient separation
      was obtained with a total analysis time of less than 60 min, including the
      extraction-purification steps. Good responses for the six pyrethroids were
      obtained in a range of 50-500 MUg L-1, with linear coefficients higher than
      0.9992. Instrumental limits of detection were between 0.22 and 0.63 MUg L-1,
      corresponding to 0.04 and 0.13 MUg kg-1 in the matrix. Detection limits in
      chicken eggs and various meat samples, calculated on spiked samples, were in the
      range 0.05-0.25 MUg kg-1 and 0.07-0.23 MUg kg-1, respectively. The validation
      results confirmed that the proposed GC-ECD method can be used as a reliable
      screening tool for the determination of pyrethroids in official check analyses.
      The method was extensively validated following the European directives,
      demonstrating its conformity in terms of selectivity, sensitivity, recovery,
      precision, and measurement uncertainty.

PMID- 30205685
TI  - Flexible Vertical p-n Diode Photodetectors with Thin N-type MoSe2 Films Solution
      Processed on Water Surfaces.
AB  - Two-dimensional (2D) nanosheets of transition metal dichalcogenides (TMDs) are of
      significant interest for potential photoelectronic applications. However, the
      fabrication of solution-processed arrays of mechanically flexible thin TMD films
      based vertical type p-n junction photodetectors over a large area is a great
      challenge. Our method is based on controlled solvent evaporation of MoSe2
      suspension spread on water surface. Single or few-layered MoSe2 nanosheets
      modified with the dispersant amine-terminated poly(styrene) (PS-NH2) were
      homogeneously deposited and stacked on water upon solvent evaporation, giving
      rise to uniform MoSe2/PS-NH2 composite films that can be readily transferred onto
      other substrates. A p-n junction vertical diode of Al/p-type Si/p-type poly(9,9
      di- n-octylfluorenyl-2,7-diyl)/n-type MoSe2 composite/Au stacked from bottom to
      top exhibited characteristic rectifying current behavior upon voltage sweep with
      a rectification ratio of 103. Subsequent illumination of near-infrared light on
      the device resulted in a substantially enhanced dark current of approximately 103
      times greater than that of the nonexposed device. The photodetection performance,
      that is, switching time, responsivity, and detectivity, were 100.0 ms, 2.5 AW-1,
      and 2.34 * 1014, respectively. Furthermore, the performance of mechanically
      flexible photodetectors devices was comparable with that of the devices
      fabricated on the hard Si substrate even after 1000 bending cycles at a bending
      diameter of 7.2 mm.

PMID- 30205686
TI  - Probing the Viscosity Dependence of Rate: Internal Friction or the Lack of
      Friction?
AB  - Deviation from the Kramers' inverse viscosity dependence of rate, k ? 1/eta, is
      often attributed to the presence of internal friction in proteins after Ansari et
      al. in 1992 showed that the folding rate could fit k ? 1/(eta + sigma) where
      sigma is considered the internal friction. Several experimental and computational
      studies thereafter used fits to Ansari's equation or extrapolated the rate to eta
      = 0 to estimate the internal friction in proteins and attributed its origin to
      various internal interactions such as ruggedness, dihedral rotation, and salt
      bridges. Here, we show that the above method to calculate the internal friction
      is incorrect since the rate in a simple model system without any internal
      friction yields a nonzero sigma. Further investigation reveals that sigma
      correlates with the relative deviation from Kramers' rate at different
      viscosities, where the deviation itself is caused due to the absence of full
      solvent friction rather than the presence of internal friction.

PMID- 30205688
TI  - Introduction: Carbohydrate Chemistry.

PMID- 30205687
TI  - Metabolism of the Strobilurin Fungicide Mandestrobin in Wheat.
AB  - The metabolic fate of a new fungicide, mandestrobin, labeled with 14C at the
      phenoxy or benzyl ring was examined in wheat after a single spray application at
      300 g/ha. Mandestrobin penetrated into foliage over time, with both radiolabels
      showing similar 14C distribution in wheat, and 2.8-3.3% of the total radioactive
      residue remained on the surface of straw at the final harvest. In foliage,
      mandestrobin primarily underwent mono-oxidation at the phenoxy ring to produce 4
      hydroxy or 2-/5-hydroxymethyl derivatives, followed by their subsequent formation
      of malonylglucose conjugates. In grain, the cleavage of its benzyl phenyl ether
      bond was the major metabolic reaction, releasing the corresponding alcohol
      derivative, while the counterpart 2,5-dimethylphenol was not detected. The
      constant RS enantiomeric ratio of mandestrobin showed its enantioselective
      metabolism to be unlikely on/in wheat.

PMID- 30205691
TI  - Relational care and co-operative endeavour - Reshaping dementia care through
      participatory secondary data analysis.
AB  - Dementia is emerging from the shadows of societal exclusion and stigma. The
      engagement within society for people who are marginalised is co-constructed
      through the everyday practices that take place between them and those around
      them. However, this is inherently political, positioning people as active and
      activist in the relationship of their lives with their communities. The research
      aimed to interrogate an existing qualitative dataset in partnership with people
      living with dementia to inform the development of a way of working with people
      with dementia that is empowering. In this qualitative secondary data analysis
      project, we (1) analysed data through two theoretical lenses: Douglas' cultural
      theory of risk and Tronto's Ethic of Care, and (2) co-analysed the data together
      with people living with dementia during 16 workshops. The design involved cycles
      of presenting, interpreting, representing and reinterpreting the data and
      findings between multiple stakeholders. We identified a granular understanding of
      the way relationships change for people with dementia and how subtle factors and
      nuanced behaviour contribute to social exclusion, or support social inclusion.
      The results support relational care through the co-operative endeavour (of co
      operative communication, co-operative action and co-operative care) in promoting
      the inclusion of people living with dementia.

PMID- 30205690
TI  - Carbon nanodots: Opportunities and limitations to study their biodistribution at
      the human lung epithelial tissue barrier.
AB  - Inhalation of combustion-derived ultrafine particles (<=0.1 MUm) has been found
      to be associated with pulmonary and cardiovascular diseases. However, correlation
      of the physicochemical properties of carbon-based particles such as surface
      charge and agglomeration state with adverse health effects has not yet been
      established, mainly due to limitations related to the detection of carbon
      particles in biological environments. The authors have therefore applied model
      particles as mimics of simplified particles derived from incomplete combustion,
      namely, carbon nanodots (CNDs) with different surface modifications and
      fluorescent properties. Their possible adverse cellular effects and their
      biodistribution pattern were assessed in a three-dimensional (3D) lung epithelial
      tissue model. Three different CNDs, namely, nitrogen, sulfur codoped CNDs ( N,S
      CNDs) and nitrogen doped CNDs ( N-CNDs-1 and N-CNDs-2), were prepared by
      microwave-assisted hydrothermal carbonization using different precursors or
      different microwave systems. These CNDs were found to possess different chemical
      and photophysical properties. The surfaces of nanodots N-CNDs-1 and N-CNDs-2 were
      positively charged or neutral, respectively, arguably due to the presence of
      amine and amide groups, while the surfaces of N,S-CNDs were negatively charged,
      as they bear carboxylic groups in addition to amine and amide groups.
      Photophysical measurements showed that these three types of CNDs displayed strong
      photon absorption in the UV range. Both N-CNDs-1 and N,S-CNDs showed weak
      fluorescence emission, whereas N-CNDs-2 showed intense emission. A 3D human lung
      model composed of alveolar epithelial cells (A549 cell line) and two primary
      immune cells, i.e., macrophages and dendritic cells, was exposed to CNDs via a
      pseudo-air-liquid interface at a concentration of 100 MUg/ml. Exposure to these
      particles for 24 h induced no harmful effect on the cells as assessed by
      cytotoxicity, cell layer integrity, cell morphology, oxidative stress, and
      proinflammatory cytokines release. The distribution of the CNDs in the lung model
      was estimated by measuring the fluorescence intensity in three different
      fractions, e.g., apical, intracellular, and basal, after 1, 4, and 24 h of
      incubation, whereby reliable results were only obtained for N-CNDs-2. It was
      shown that N-CNDs-2 translocate rapidly, i.e., >40% in the basal fraction within
      1 h and almost 100% after 4 h, while ca. 80% of the N-CNDs-1 and N,S-CNDs were
      still located on the apical surface of the lung cells after 1 h. This could be
      attributed to the agglomeration behavior of N-CNDs-1 or N,S-CNDs. The surface
      properties of the N-CNDs bearing amino and amide groups likely induce greater
      uptake as N-CNDs could be detected intracellularly. This was less evident for N,S
      CNDs, which bear carboxylic acid groups on their surface. In conclusion, CNDs
      have been designed as model systems for carbon-based particles; however, their
      small size and agglomeration behavior made their quantification by fluorescence
      measurement challenging. Nevertheless, it was demonstrated that the surface
      properties and agglomeration affected the biodistribution of the particles at the
      lung epithelial barrier in vitro.

PMID- 30205692
TI  - Mediating effect of spiritual coping strategies and family stigma stress on
      caregiving burden and mental health in caregivers of persons with dementia.
AB  - Background A considerable number of the persons living with dementia rely on
      family members for care and assistance when performing activities of daily
      living. As a result, caregivers may be at increased risk for mental health
      problems such as depression, anxiety and caregiver burden. This study examined if
      and how spiritual coping and stigma-related family stress impacted the
      associations between the patient activities of daily living impairment and
      caregiver mental health. Methods Using a longitudinal design, 664 caregivers were
      assessed at baseline for spiritual coping strategies and family stigma stress,
      along with patients' instrumental activities of daily living and cognitive
      functioning. After 12 months, caregivers were assessed for depressive and anxiety
      symptoms, caregiver burden, and quality of life (physical and mental). Sequential
      mediation of spiritual coping strategies and stigma-related family stress on the
      relationship between patient instrumental activities of daily living and
      caregiver mental health outcomes was examined using the PROCESS macro statistical
      method. Results Participants had been caring for someone with dementia for an
      average of 46.4 (SD, 16.9) months and 63% of caregivers were female. There were
      significant indirect associations between patient instrumental activities of
      daily living and caregiver anxiety, depression, caregiving burden, and the mental
      health component of quality of life. Spiritual coping and stigma-related stress
      mediated these associations (-0.54<b<-0.02). Overall, 26%, 41%, 49%, and 59% of
      the variances of caregiving burden, anxiety, depression, and mental functioning,
      respectively, were explained using the sequential mediation models. Conclusions
      Spiritual coping and stigma-related stress appear to mediate the relationship
      between the patient instrumental activities of daily living impairment and
      caregiver psychological health. These factors should be considered when
      addressing mental health problems experienced by caregivers.

PMID- 30205693
TI  - Do Smartphone Applications Hold the Secret to Reducing Hypoglycemia in Type 1
      Diabetes?
AB  - In this article in JDST, Feuerstein-Simon and colleagues examine use of a
      smartphone app in improving hypoglycemia awareness in type 1 diabetes (T1D). They
      conclude that their smartphone app, HypoMapTM, has the potential to increase
      hypoglycemia awareness and reduce time spent with hypoglycemia in a cohort of
      long-standing patients with type 1 diabetes. The underlying assumption is that if
      patients can identify the precipitating cause, they can recognize symptoms better
      and potentially change behavior to prevent future hypoglycemic events. Potential
      limitations of this intervention include technical issues, patient burden from
      data entry with use of an app, and concern that this type of intervention may not
      be sustainable over time. While results of this pilot study suggest HypoMap may
      be an effective intervention in preventing hypoglycemia, further studies of
      increased sample size are needed to confirm these findings.

PMID- 30205694
TI  - Relationship of Christian Beliefs to Attitudes Toward People With Mental Illness.
AB  - This study assessed the influence of Christian beliefs on attitudes toward people
      with mental illness. Participants (N=204) provided demographic information and
      completed the Christian Orthodoxy Scale, the Religious Fundamentalism Scale, and
      the Attitudes to Mental Illness Questionnaire. Participants read vignettes of a
      person with a mental illness (schizophrenia), a general medical illness
      (diabetes), and a control condition (practicing Christian) and rated them on five
      criteria representing stigmatizing attitudes. The data were analyzed by
      sequential multiple regression. Religious fundamentalism, but not Christian
      orthodoxy, was a significant predictor of stigmatizing attitudes toward a person
      with mental illness. Consistent with past research, neither religious
      fundamentalism nor Christian orthodoxy were significant predictors of
      stigmatizing attitudes toward a general medical illness. As predicted, both
      religious fundamentalism and Christian orthodoxy were significant predictors of
      positive attitudes toward a practicing Christian. Sensitivity and discourse
      regarding stigmatization and deeply held fundamental religious beliefs are needed
      among mental health professionals, religious leaders, and laypersons.

PMID- 30205695
TI  - Humor Associated With Positive Outcomes in Individual Psychotherapy.
AB  - Considerable anecdotal evidence points to the usefulness of humor in the
      therapeutic process, but empirical evidence is lacking. The purpose of this
      study, conducted in Belgium, was to search for an association between humor and
      therapy outcomes in a population of 110 adult psychotherapy clients who attended
      at least 10 therapy sessions. Clients and their therapist evaluated the frequency
      and intensity of humorous events, as well as therapy effectiveness, therapeutic
      alliance, perceived hope, and pleasure in participating in therapy sessions. A
      strong positive correlation was observed between humor and therapy effectiveness,
      from both client (rs=0.40; p<0.001) and therapist perspectives (rs=0.37;
      p<0.001). The link between humor and therapy effectiveness remained significant
      in subgroups of clients with more severe illness, although these clients reported
      less humor in their therapy sessions. Further research is needed to determine
      whether humor enhances outcomes or whether positive outcomes trigger occurrence
      of humor.

PMID- 30205696
TI  - Prediction of Liver Disease, AIDS, and Mortality Based on Discordant Absolute and
      Relative Peripheral CD4 T Lymphocytes in HIV/Hepatitis C Virus-Coinfected
      Individuals.
AB  - Hepatitis C virus (HCV)-induced liver fibrosis and splenomegaly may lead to
      discordance between absolute numbers and percentages of lymphocytes and
      subpopulations because of sequestration. We investigated lymphocyte discordance
      in HIV/HCV-coinfected individuals and its relationship to progression to liver
      disease, AIDS, and all-cause mortality. This is an observational retrospective
      cohort study. Adjusted hazard ratios (aHRs) with 95% confidence intervals (95%
      CIs) associated with liver disease, AIDS, or mortality were computed by time
      updated Cox proportional hazards regression. Of 380 HIV/HCV-coinfected adult
      individuals followed for a median of 8.2 years, 360 individuals had a median of
      11 discordant measurements corresponding to 5,080 of 9,091 paired samples (56%).
      Discordance alone was not associated with any of the outcomes. By multivariable
      analysis, a doubling of absolute or percentage CD4 cells was associated with
      comparable lower risks of mortality (aHR: 0.60, 95% CI: 0.53-0.67, p < .0001 and
      aHR: 0.67, 95% CI: 0.56-0.79, p < .0001, respectively). Higher CD4/CD8 ratio was
      associated with a lower mortality risk (aHR: 0.39, 95% CI: 0.22-0.71 per
      doubling, p = .002). Only absolute CD4 cell measurements predicted AIDS.
      Development of liver disease was not predicted by total lymphocyte count or
      subpopulations. Despite a high prevalence of lymphocyte-subpopulation discordance
      with HIV/HCV coinfection, absolute CD4 cell count predicted mortality and AIDS,
      whereas CD4 percentage only predicted mortality. Neither CD4 T lymphocyte count
      nor CD4 percentage was associated with liver disease in this cohort. These
      findings may be necessary and useful in countries where antiretroviral treatment
      is not initiated for all HIV-infected individuals.

PMID- 30205697
TI  - Effect of Audit and Feedback on Physician Adherence to Clinical Practice
      Guidelines for Pneumonia and Sepsis.
AB  - The objective was to estimate the effect of feedback with blinded peer comparison
      on emergency physician adherence to guidelines for appropriate antibiotic
      administration for inpatient pneumonia and completion of the 3-hour Surviving
      Sepsis Bundle for severe sepsis. The authors performed a quasi-experiment using a
      stepped wedge design at a single urban safety net hospital. Attending emergency
      physicians were randomized into 6 clusters. Once a cluster crossed into the
      intervention group, physicians in that cluster began receiving detailed feedback
      with blinded peer comparison on their adherence to guidelines for pneumonia and
      sepsis. Feedback with blinded peer comparison significantly improved guideline
      adherence from 52% without feedback to 65% with feedback (difference = 13%, 95%
      confidence interval = 4% to 22%). In adjusted analyses, the odds of providing
      guideline adherent care were 1.8 (95% confidence interval = 1.01-3.2) after the
      introduction of feedback with blinded peer comparison. Feedback with blinded peer
      comparison significantly improved emergency physician guideline adherence.

PMID- 30205698
TI  - Testosterone replacement therapy and hospitalization rates in men with COPD.
AB  - Testosterone deficiency is common in men with chronic obstructive pulmonary
      disease (COPD) and may exacerbate their condition. Research suggests that
      testosterone replacement therapy (TRT) may have a beneficial effect on
      respiratory outcomes in men with COPD. To date, however, no large-scale
      nationally representative studies have examined this association. The objective
      of the study was to assess whether TRT reduced the risk of respiratory
      hospitalizations in middle-aged and older men with COPD. We conducted two
      retrospective cohort studies. First, using the Clinformatics Data Mart-a database
      of one of the largest commercially insured populations in the United States-we
      examined 450 men, aged 40-63 years, with COPD who initiated TRT between 2005 and
      2014. Second, using the national 5% Medicare database, we examined 253 men, aged
      >=66 years, with COPD who initiated TRT between 2008 and 2013. We used difference
      in-differences (DID) statistical modeling to compare pre- versus post-respiratory
      hospitalization rates in TRT users versus matched TRT nonusers over a parallel
      time period. DID analyses showed that TRT users had a greater relative decrease
      in respiratory hospitalizations compared with nonusers. Specifically, middle-aged
      TRT users had a 4.2% greater decrease in respiratory hospitalizations compared
      with nonusers (-2.4 decrease vs. 1.8 increase; p = 0.03); and older TRT users had
      a 9.1% greater decrease in respiratory hospitalizations compared with nonusers (
      0.8 decrease vs. 8.3 increase; p = 0.04). These findings suggest that TRT may
      slow disease progression in patients with COPD. Future studies should examine
      this association in larger cohorts of patients, with particular attention to
      specific biological pathways.

PMID- 30205699
TI  - Regional differences in anti-TNF-alpha therapy and surgery in the treatment of
      inflammatory bowel disease patients: a Norwegian nationwide cohort study.
AB  - BACKGROUND AND AIMS: During the last decades, substantial progress has been made
      in both medical and surgical treatment of inflammatory bowel disease (IBD). The
      aim of this study was to determine the use of anti-TNFs and surgery during the
      first 3 years after diagnosis in IBD patients across the four health regions in
      Norway using nationwide patient registry data. METHODS: This study used
      nationwide data from the Norwegian Patient Registry. Cumulative incidence of anti
      TNF exposure and major surgery was calculated for patients diagnosed in 2010
      2012. The analyses were stratified by diagnosis and health region. All patients
      were followed for an equal period of 3 years from diagnosis. RESULTS: The study
      population included 8,257 IBD patients first registered between 2010 and 2012, of
      whom 2,829 were diagnosed with Crohn's disease (CD) and 5,428 with ulcerative
      colitis (UC). Across Norway's health regions, the cumulative incidence of major
      surgery after 3 years varied from 11.4% to 17.1% for CD and from 4.6% to 6.9% for
      UC. The cumulative incidence of anti-TNF exposure varied from 20.9% to 31.4% for
      CD and from 8.0% to 13.5% for UC. The region with the lowest anti-TNF use had the
      highest surgery rates for both UC and CD. CONCLUSIONS: Cumulative incidence of
      anti-TNF exposure and surgery varied significantly across Norway's health regions
      during the three first years after IBD diagnosis.

PMID- 30205701
TI  - ALBI and P-ALBI grade in Child-Pugh A patients treated with drug eluting embolic
      chemoembolization for hepatocellular carcinoma.
AB  - Background Treatment outcome for hepatocellular carcinoma (HCC) is related to
      tumor burden and liver function. Grading systems assessing liver function need
      validation in different clinical settings. Purpose To evaluate drug-eluting
      embolic transarterial chemoembolization (DEE-TACE) in Child-Pugh A HCC with
      respect to albumin-bilirubin (ALBI) and platelet-albumin-bilirubin (P-ALBI)
      grade. Material and Methods Forty-nine patients with Child-Pugh class A,
      diagnosed with HCC and allocated to DEE-TACE treatment, were retrospectively
      analyzed regarding tumor and treatment characteristics, radiological response
      (mRECIST) one month post treatment, overall survival (OS), and adverse events
      (AEs; CTCAE, grades >=3) with respect to ALBI and P-ALBI grade. Results There
      were 21 ALBI 1 patients, 29 P-ALBI 1 patients, and 19 patients were both ALBI and
      P-ALBI 1. Objective response rate was 74% with no statistically significant
      difference for ALBI (1 vs. 2; P = 0.08), or P-ALBI (1 vs. 2; P = 0.49). OS was
      14.8 months (range = 1.7-62.0; ALBI 1 vs. 2: P = 0.08; P-ALBI 1 vs. 2: P =
      0.003). OS in responders with ALBI 1 and 2 was 28.9 vs.10.2 months ( P = 0.02),
      and P-ALBI 1 and 2 was 26.7 vs. 8.6 months ( P < 0.001). In multivariate
      analyses, both ALBI 2 (HR = 2.4, P = 0.02) and P-ALBI 2 (HR = 3.3, P < 0.01) were
      negative prognostic factors for survival. There were 15 AEs in 13 patients, with
      hepatic failure only occurring in ALBI 2 and P-ALBI 2 patients. Conclusion P-ALBI
      grade 1 and 2 differentiated survival in Child-Pugh A patients treated with DEE
      TACE. Both grading systems can differentiate survival in patients responding to
      treatment.

PMID- 30205703
TI  - Incidence and risk factors of facet joint violation following percutaneous
      kyphoplasty for osteoporotic vertebral compression fractures.
AB  - Background Percutaneous kyphoplasty (PKP) has been widely used to osteoporotic
      vertebral compression fractures (OVCFs). No previous investigations have reported
      the incidence and risk factors of facet joint violation (FJV) caused by PKP.
      Purpose To determine the incidence and risk factors of FJV following PKP in
      patients with OVCFs. Material and Methods We reviewed a total of 153 patients who
      underwent bilateral PKP. Postoperative computed tomography (CT) scans were
      assessed to determine the degree of FJV owing to invasion by a puncture trocar.
      Clinical outcomes, including visual analogue scale (VAS) scores and Oswestry
      Disability Index (ODI) scores, were collected from all patients. Clinical and
      radiological data were analyzed to identify the risk factors for FJV. Results FJV
      caused by PKP affected 18.9% of patients and 9.6% of facet joints; approximately
      3.9% and 5.7% of facet joints were considered to have grade 1 and grade 2
      violations, respectively. There were significant differences between the FJV and
      non-FJV groups in VAS and ODI scores after surgery. Significant differences were
      found with respect to the facet joint angle (FJA), the pedicle diameter (PD), and
      the distance from the entry point to the facet joint space (DEF). Multiple
      logistic regression analysis indicated that an FJA > 55 degrees , a PD < 5 mm,
      and a DEF < 5 mm were independent risk factors for FJV. Conclusion The placement
      of a puncture trocar can cause FJV in patients with OVCFs and impact clinical
      outcomes after PKP. Special attention should be given to patients with an FJA >
      55 degrees , a PD < 5 mm, and a DEF < 5 mm.

PMID- 30205700
TI  - Isoform-specific activities of the regulatory subunits of phosphatidylinositol 3
      kinases - potentially novel therapeutic targets.
AB  - INTRODUCTION: The main regulatory subunits of Class IA phosphatidylinositol 3
      kinase (PI3K), p85alpha and p85beta, initiate diverse cellular activities
      independent of binding to the catalytic subunit p110. Several of these signaling
      processes directly or indirectly contribute to a regulation of PI3K and could
      become targets for therapeutic efforts. Areas covered: This review will highlight
      two general areas of p85 activity: (1) direct interaction with regulatory
      proteins and with determinants of the cytoskeleton, and (2) a genetic analysis by
      deletion and domain switches identifying new functions for p85 domains. Expert
      Opinion: Isoform-specific activities of regulatory subunits have long been at the
      periphery of the PI3K field. Our understanding of these unique functions of the
      regulatory subunits is fragmentary and raises many important questions. At this
      time, there is insufficient information to translate this knowledge into the
      clinic, but some tempting targets have emerged that could move the field forward
      with the help of novel technologies in drug design and identification.

PMID- 30205704
TI  - In vitro T2 relaxivities of the Gd-based contrast agents (GBCAs) in human blood
      at 1.5 and 3 T.
AB  - Background The availability of data in the medical literature for the T2
      relaxivities of the Gd-based contrast agents (GBCAs) is limited. A comprehensive
      comparison between the agents available commercially (other than in Europe) is
      lacking, with no data available that most closely reflect the clinic, which is in
      human whole blood at body temperature. Purpose To complement the existing
      literature by determining T2 relaxivity data for eight GBCAs in vitro. Material
      and Methods The relaxivities of eight GBCAs diluted in human whole blood at 1.5
      and 3 T were determined at 37 +/- 0.5  degrees C. Gd was in the range of 0-4 mM.
      Multi-echo sequences with variable echo times were acquired using a phantom
      containing a dilution series with each agent, and SigmaPlot 12.0 was used to
      calculate the R2 relaxation rate and finally r2. Statistical comparisons between
      agents and field strengths were conducted. Results The relationship between R2
      vs. Gd was observed to be linear at 1.5 and 3 T, with a mild increase in r2 from
      1.5 to 3 T for all GBCAs. T2 relaxivity data were compared with prior results.
      The GBCAs are closely clustered into two groups, with higher r2 noted for the two
      lipophilic (those with partial hepatobiliary excretion) compounds. Conclusion The
      r2 values at 1.5 and 3 T, determined for the eight GBCAs still clinically
      available (other than in Europe), provide a definitive baseline for future
      evaluations, including theoretical calculations of signal intensity and their
      clinical impact on T2-weighted scans.

PMID- 30205705
TI  - Contribution of 18F-FDG PET/CT in a case-mix of fever of unknown origin and
      inflammation of unknown origin: a meta-analysis.
AB  - Background Fever of unknown origin (FUO) and inflammation of unknown origin (IUO)
      are challenging medical problems. Previous studies have shown that 18F
      fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG
      PET/CT) plays an important role in the diagnosis of FUO, but few studies have
      explored this diagnostic technique in relation to IUO. Purpose To systematically
      review and perform a meta-analysis of published data on the diagnostic
      performance of PET/CT in the diagnosis of FUO and IUO. Material and Methods A
      comprehensive literature search was performed in accordance with the Preferred
      Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines
      published in March 2018. Meta-analysis of diagnostic performance was performed
      using STATA 12.0 software. Subgroup analysis was performed by stratification
      based on study design, number of patients, geographic area, and final diagnosis
      based on 18F-FDG PET/CT. Meta-regression analyses were performed to recognize
      heterogeneity. Results Our meta-analysis included 23 studies, comprising a total
      sample size of 1927 patients. The pooled diagnosis performance was calculated
      with a per-patient-based analysis: sensitivity = 0.84 (95% confidence interval
      [CI] = 0.79-0.89), specificity = 0.63 (95% CI = 0.49-0.75), positive likelihood
      ratio = 2.3 (95% CI = 1.5-3.4), negative likelihood ratio = 0.25 (95% CI = 0.16
      0.38), diagnostic odds ratio = 9 (95% CI = 4.0-20), and AUC = 0.84 (95% CI = 0.81
      0.87). Conclusion In patients with non-specific symptoms and signs, 18F-FDG
      PET/CT is very helpful for recognizing and excluding diseases, directing further
      diagnostic decisions, and avoiding unnecessary invasive examinations. We
      recommend that 18F-FDG PET/CT should be considered among the first-line
      diagnostic tools for patients with FUO and IUO.

PMID- 30205707
TI  - A Study of Relationships Between Content in Documents From Health Service
      Operational Plans and Documents From the Planning of New Healthcare Environments.
AB  - AIM: The aim was to investigate the content and quality of the governing
      documents created in the planning and design phase of new healthcare environments
      and in the related healthcare strategic and operational plans. BACKGROUND:
      Quality deficits in buildings can often be traced back to the initial stages in
      the planning and design phase. Although large investments have been made to
      improve the process of planning new healthcare environments and linking the
      requirements to health service strategies, healthcare organizations rarely relate
      their strategy goals to the built environment. METHOD: A retrospective review of
      documents created in the planning and design stages of new healthcare
      environments and the operational plans of the target organizations was conducted.
      RESULTS: The organizational operational plans did not contain any statements or
      information about the built environment or how a building could or should support
      the organization's goals. Important information was frequently absent from the
      documents governing the planning and design of buildings. The documents lacked
      information about what and how to follow-up and what to measure once a
      construction project had been completed. There were no references to evidence.
      CONCLUSIONS: Poor documentation might undermine the quality of the planning and
      design phase and ultimately the opportunity to create environments that support
      health outcomes. Therefore, more emphasis must be placed on the importance of
      documentation but above all to strengthen and clarify the relationship between
      the healthcare organization strategy to achieve an effective and efficient care
      process and the intention made in the planning and design process.

PMID- 30205706
TI  - A Unique Presentation of Scaphocapitate Syndrome With Extrusion Into the Carpal
      Tunnel: A Case Report.
AB  - BACKGROUND: Scaphocapitate syndrome is a rare variety of perilunate instability,
      described as a trans-scaphoid, trans-capitate fracture, with rotation of the
      capitate head either 90 degrees  or 180 degrees . METHODS: We present a unique
      case of scaphocapitate syndrome in which the rotated proximal capitate fragment
      expelled into the carpal canal. RESULTS: The capitate head was extricated from
      the carpal tunnel via the volar approach, and was anatomically aligned and fixed
      through the dorsal approach using two 2.0 mm headless compression screws. The
      scaphoid fracture was then also reduced through the dorsal approach and
      stabilized with a 2.5 mm headless compression screw. All intercarpal ligaments
      appeared intact. CONCLUSIONS: Volar dislocation of the proximal capitate into the
      carpal tunnel in scaphocapitate syndrome presents a unique challenge that can be
      addressed with a combined volar and dorsal approach.

PMID- 30205708
TI  - Macular edema after cataract surgery in eyes with and without pseudoexfoliation
      syndrome.
AB  - BACKGROUND: The purpose of the study was to identify macular edema after cataract
      surgery in eyes with and without pseudoexfoliation syndrome. The study was a post
      hoc analysis of a randomized, double-blind, prospective single-center study.
      Patients were enrolled between January 2016 and October 2016 as per the national
      guidelines for the management of cataract in the Department of Ophthalmology,
      Kymenlaakso Central Hospital, Kotka, Finland. METHODS: One hundred and fifty-six
      eyes of 149 patients undergoing routine cataract surgery. Postoperatively anti
      inflammatory medication was either dexamethasone (N = 78) or diclofenac (N = 78).
      Spectral domain optical coherence tomography imaging and laser flare meter
      measurement of the anterior chamber were conducted before surgery and at the
      control visit 28 days postoperatively. RESULTS: Baseline variables were
      comparable between eyes with pseudoexfoliation syndrome (N = 32) and those
      without (N = 124), except for intraocular pressure ( P = 0.002) and glaucoma
      medication ( P < 0.001). In patients having pseudoexfoliation syndrome, central
      retinal thickness increase (mean +/- standard error of the mean) was 63.3 +/-
      35.5 MUm for dexamethasone and 17.6 +/- 5.8 MUm for diclofenac, compared to 28.9
      +/- 8.0 MUm ( P = NS) and 6.9 +/- 1.3 MUm ( P = 0.014) in eyes without
      pseudoexfoliation syndrome, respectively. Aqueous flare at 28 days was 25.8 +/-
      5.4 pu/ms for patients with pseudoexfoliation syndrome and 18.3 +/- 1.8 pu/ms for
      those without ( P = 0.030). Best corrected visual acuity gain and best corrected
      visual acuity at 28 days were less in patients having pseudoexfoliation syndrome
      compared to those without (0.39 +/- 0.07 vs 0.59 +/- 0.03 decimals, P = 0.007;
      and 0.77 +/- 0.06 vs 0.92 +/- 0.03 decimals, P = 0.008, respectively).
      CONCLUSION: Eyes with pseudoexfoliation syndrome may be predisposed to an
      increased aqueous flare and macular edema after cataract surgery. This study
      outlines the need to determine the optimal anti-inflammatory medication after
      cataract surgery in patients with pseudoexfoliation syndrome.

PMID- 30205709
TI  - Oncolytic Activity of a Novel Influenza A Virus Carrying Granulocyte-Macrophage
      Colony-Stimulating Factor in Hepatocellular Carcinoma.
AB  - Oncolytic virotherapy is a promising strategy for the treatment of cancer.
      Influenza A virus has shown potential as an oncolytic agent. In this study, a
      recombinant PR8 influenza viral vector, called delNS1-GM-CSF, was generated with
      a partial deletion in NS and the granulocyte-macrophage colony-stimulating factor
      (GM-CSF) coding sequence inserted into the influenza nonstructural protein 1
      gene. The morphological characteristics of delNS1-GM-CSF were examined. The
      delNS1-GM-CSF virus replicated well in various cell lines, including MDCK, A549,
      SMCC7721, and HepG2 cells. Moreover, selective cytotoxicity of the virus was
      observed in various hepatocellular carcinoma (HCC) cell lines, while no effect
      was demonstrated in the normal liver cell line LO2, as indicated by 3-(4,5
      dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide and crystal violet assays.
      Importantly, using a model based on the growth of HepG2 cells as a xenograft in
      nude mice, it was found that a reassortant delNS1-GM-CSF virus inhibited tumor
      growth significantly following intratumoral injection in a dose-dependent manner.
      Ex vivo results showed that the tumor inhibition efficacy of delNS1-GM-CSF was
      observed in HCC clinical samples. Taken together, these results are the first to
      demonstrate that influenza A viruses may have potential as oncolytic
      virotherapeutic agents against HCC.

PMID- 30205710
TI  - Gas-phase metal ion chelation investigated with IRMPD spectroscopy: A brief
      review of Robert Dunbar's contributions.
AB  - With the passing of Prof. Robert C. Dunbar on 31 October 2017, the field of ion
      chemistry lost one of its modern heroes. Throughout his career in mass
      spectrometry, two of his main research interests involved the interaction of
      trapped ions with electromagnetic radiation and the chelation motifs of metal
      ions with organic ligands. The focus of his early career was on the fundamental
      processes that take place in molecules upon ultraviolet and infrared excitation.
      From 2003 to 2017, his scientific interests shifted to more structural questions,
      notably to resolving the structures and binding motifs of metal ion chelation
      complexes by application of infrared photodissociation spectroscopy. These
      experiments were carried out during numerous visits to the (Free Electron Laser
      for Infrared eXperiments) (FELIX) facility in the Netherlands and were
      complemented by extensive theoretical investigations by Rob. As a tribute to our
      friend, we present in this contribution a brief review of this work.

PMID- 30205711
TI  - Kallistatin Inhibits Atherosclerotic Inflammation by Regulating Macrophage
      Polarization.
AB  - Kallistatin (KS) has been recognized as a plasma protein with anti-inflammatory
      functions. Macrophages are the primary inflammatory cells in atherosclerotic
      plaques. However, it is unknown whether KS plays a role in macrophage development
      and the pathogenesis of atherosclerosis. This study investigated the role of KS
      in macrophage development, a key pathological process in atherosclerosis. An
      atherosclerosis model was established in ApoE-/- mice via partial left carotid
      artery (PLCA) ligation. An adenovirus vector (Ad. HKS) containing the human KS
      gene was delivered via the tail vein before PLCA ligation. The mice were divided
      into two groups: the PLCA + Ad. HKS and PLCA + adenovirus vector (Ad. Null)
      groups and followed for 2 and 4 weeks. Human KS was expressed in the mice after
      KS gene delivery. In addition, KS significantly inhibited plaque formation and
      reduced inflammation in the plaques and liver 4 weeks after gene delivery.
      Moreover, KS gene delivery significantly increased the expression of interleukin
      10 and Arginase 1, which are M2 macrophage markers, and reduced the expression of
      inducible nitric oxide synthase and monocyte chemotactic protein 1, which are M1
      macrophage markers. Furthermore, in cultured RAW 264.7 macrophages, KS
      significantly stimulated M2 marker expression and differentiation and decreased
      M1 marker expression, as determined by flow cytometry and real-time polymerase
      chain reaction. These effects were blocked by Kruppel-like factor 4 small
      interfering RNA oligonucleotides. These findings demonstrate that KS inhibits
      atherosclerotic plaque formation and regulates M1/M2 macrophage polarization via
      Kruppel-like factor 4 activation.

PMID- 30205712
TI  - The application of gene silencing in proteomics: from laboratory to clinic.
AB  - INTRODUCTION: Since the completion of genome sequencing, gene silencing
      technologies have emerged as powerful tools to study gene functions in various
      biological processes, both in vivo and in vitro. Moreover, they have also been
      proposed as therapeutic agents to inhibit selected genes in a variety of
      pathological conditions, such as cancer, neurodegenerative, and cardiovascular
      diseases. Area covered: This review summarizes the mechanisms of action and
      applications of genome editing tools, from RNA interference to clustered
      regularly interspaced short palindromic repeats-based systems, in research and in
      clinics. We describe their essential role in high-throughput genetic screens and,
      in particular, in functional proteomics studies, to identify diagnostic markers
      and therapeutic targets. Indeed, gene silencing and proteomics have been
      extensively integrated to study global proteome changes, posttranslational
      modifications, and protein-protein interactions. Expert commentary: Functional
      proteomics approaches that leverage gene silencing tools have been successfully
      applied to examine the role of several genes in various contexts, leading to a
      deeper knowledge of biological pathways and disease mechanisms. Recent
      developments of gene silencing tools have improved their performance, also in
      terms of off-targets effects reduction, paving the way for a wider therapeutic
      application of these systems.

PMID- 30205713
TI  - From stigma to the spotlight: A need for patient-centred incontinence care.
AB  - Incontinence is not a single disorder but a family of related conditions with
      different etiologies and treatments; it is a chronic disability that carries an
      enormous stigma. In few disorder/treatment pairings, there is the need to
      reinvent care more urgent and clear than in the area of incontinence. Patient
      centred care has been realized to improve outcomes, quality of care, and patient
      satisfaction while concurrently reducing healthcare costs. To improve continence
      care and move it away from "cleaning up accidents" to a patient-centred care
      model, in which the disorder is managed to best practice guidelines, does not
      require investigative or developmental prowess but a simple, concentrated effort
      to diffuse existing knowledge to close the knowledge gaps, both at the clinical
      language level for clinical nurses and family physicians, as the gatekeepers to
      specialist care, and in simplified layperson's language for the healthcare
      worker, family carer, and person living with incontinence.

PMID- 30205714
TI  - The Quantitative Anatomy of the Dorsal Scapholunate Interosseous Ligament.
AB  - BACKGROUND: The anatomy of the scapholunate interosseous ligament (SLIL) has been
      described qualitatively in great detail, with recognition of the dorsal
      component's importance for carpal stability. The purpose of this study was to
      define the quantitative anatomy of the dorsal SLIL and to assess the use of high
      frequency ultrasound to image the dorsal SLIL. METHODS: We used high-frequency
      ultrasound imaging to evaluate 40 wrists in 20 volunteers and recorded the radial
      ulnar (length) and dorsal-volar (thickness) dimensions of the dorsal SLIL and the
      dimensions of the scapholunate interval. We assessed the use of high-frequency
      ultrasound by comparing the length and thickness of the dorsal SLIL on ultrasound
      evaluation and open dissection of 12 cadaveric wrists. Student's t test was used
      to assess the relationship between measurements obtained on cadaver ultrasound
      and open dissection. RESULTS: In the volunteer wrists, the mean dorsal SLIL
      length was 7.5 +/- 1.4 mm and thickness was 1.8 +/- 0.4 mm; the mean scapholunate
      interval was 5.0 mm dorsally and 2.5 mm centrally. In the cadaver wrists, there
      was no difference in dorsal SLIL length or thickness between ultrasound and open
      dissection. CONCLUSIONS: The dorsal SLIL is approximately 7.5 mm long and 1.8 mm
      thick. These parameters may be useful in treatment of SLIL injuries to restore
      the native anatomy. High-frequency ultrasound is a useful imaging technique to
      assess the dorsal SLIL, although further study is needed to assess the use of
      high-frequency ultrasound in detection of SLIL pathology.

PMID- 30205715
TI  - Application of Ultrasound-Targeted Microbubble Destruction-Mediated Exogenous
      Gene Transfer in Treating Various Renal Diseases.
AB  - Chronic renal disease or acute renal injury could result in end-stage renal
      disease or renal failure. Sonoporation, induced by ultrasound-targeted
      microbubble destruction (UTMD), has evolved as a new technology for gene
      delivery. It increases the transfection efficiency of the genes into target
      kidney tissues. Moreover, UTMD-mediated gene delivery can directly repair the
      damaged tissues or improve the recruitment and homing of stem cells in the
      recovery of injured tissues, which has the potential to act as a non-viral and
      effective method to current gene therapy. This article reviews the mechanisms and
      applications of UTMD in terms of renal disease, including diabetic nephropathy,
      renal carcinoma, acute kidney injury, renal interstitial fibrosis, nephrotoxic
      nephritis, urinary stones, and acute rejection.

PMID- 30205716
TI  - Interface fluid syndrome secondary to endothelial failure due to toxic anterior
      segment syndrome after cataract surgery.
AB  - PURPOSE: To present a case of previous laser in situ keratomileusis with
      interface fluid syndrome secondary to toxic anterior segment syndrome following
      cataract surgery. CASE REPORT: A 52-year-old woman, complaining blurred vision in
      her right eye for 18 months after cataract surgery, was referred to our clinic.
      She was diagnosed with toxic anterior segment syndrome, postoperatively, which
      resolved in 3 days. She had a history of laser in situ keratomileusis surgery 15
      years ago. Slit-lamp examination of the right eye showed corneal haze, limited to
      laser in situ keratomileusis flap. The patient was diagnosed with interface fluid
      syndrome secondary to endothelial decompensation due to toxic anterior segment
      syndrome. Descemet's membrane endothelial keratoplasy was performed along with
      full thickness fenestrations in the laser in situ keratomileusis flap to the
      right eye of the patient. The fluid was resolved in 1 week and visual acuity was
      improved rapidly. CONCLUSION: This case shows the importance of considering the
      diagnosis and determining the specific etiology of interface fluid syndrome, even
      years after the laser in situ keratomileusis surgery, when endothelial cell
      function has been compromised with any factor, such as intraocular surgery and
      its complications.

PMID- 30205717
TI  - Phenolic content and some physical properties of dried broccoli as affected by
      drying method.
AB  - Broccoli samples ( Brassica oleracea) with an initial moisture content of 82.87%
      (wb) were dried using microwave technology (18, 36, and 54 W/g). Convective
      drying was used as a control group. The dependent variables investigated in the
      study were phenolic content, color, rehydration capacity, and microstructure of
      broccoli samples. Moreover, the best fitting thin layer model to the experimental
      moisture ratio was determined. The phenolic contents were found as 892.4, 740.6,
      and 759.8 mg gallic acid/100 g dry matter for fresh, convective dried, and
      microwave (MW) dried at 54 W/g broccoli samples, respectively. The total phenolic
      content of samples dried at 54 W/g was closest to fresh samples compared to other
      MW power intensities and convective drying. A similar result was obtained for
      color values too. L*, a*, and b* of microwave-dried samples at 54 W/g were
      comparable to fresh broccoli. Another important result obtained from the study
      was the insignificant effect of drying conditions on rehydration capacity. In
      addition, it was found that microwave power had a positive effect on drying time;
      as the microwave powers applied were compared, the shortest drying time was
      reached at 54 W/g. When the process durations of microwave drying and convective
      drying were compared, it can be reported that a much lower process time for
      microwave drying was obtained with respect to convective drying. Drying in
      microwave oven has reduced the drying time by 49-52%. In the light of the results
      obtained, it may be declared that it is possible to produce high-quality dried
      broccoli samples in a very short time by using microwave drying at 54 W/g.

PMID- 30205718
TI  - An examination of mindfulness skills in terms of affect tolerance among
      individuals with elevated levels of health anxiety.
AB  - BACKGROUND AND OBJECTIVES: Affect tolerance factors, including anxiety
      sensitivity, intolerance of uncertainty, and emotional distress tolerance, have
      been implicated in the exacerbation of health anxiety. Therefore, identifying
      methods to improve affect tolerance in health anxious populations is imperative.
      Despite the link between mindfulness and greater affect tolerance in non-clinical
      populations, no work has examined the role of mindfulness skills in terms of
      affect tolerance among individuals with elevated health anxiety. The aim of the
      current study was to examine the unique contribution of mindfulness skills in
      terms of distress tolerance, anxiety sensitivity, and intolerance of uncertainty.
      METHODS: Participants were 218 undergraduates with clinically elevated levels of
      health anxiety (75.7% female; Mage = 19.53, SD = 3.16, Range = 18-45) who
      completed self-report measures for course credit. RESULTS: Findings indicated
      that, after controlling for theoretically relevant covariates, greater acting
      with awareness, non-judgment, and non-reactivity were uniquely associated with
      greater distress tolerance, and greater non-reactivity was associated with lower
      levels of intolerance of uncertainty. Though none of the mindfulness skills
      emerged as specific individual predictors of anxiety sensitivity, these skills
      collectively accounted for unique variance in anxiety sensitivity. CONCLUSIONS:
      These findings suggest that mindfulness skills may be helpful in targeting affect
      tolerance factors among individuals with elevated health anxiety.

PMID- 30205719
TI  - The Flexor Pollicis Longus Tendon Does Not Lie Parallel to the Thumb Metacarpal.
AB  - BACKGROUND: Repair of the flexor pollicis longus (FPL) tendon by tendon retriever
      can be challenging because of uncertainty of the optimal direction. This study
      aims to describe the FPL tendon path in the thenar eminence. METHODS: In 18 hands
      of 9 cadavers, the angle of the FPL tendon was, after dissection, measured in
      relation to the axis formed between the metacarpophalangeal (MCP) joint of the
      thumb and the dorsal carpometacarpal joint (MC1-axis) and the axis formed between
      the second MCP joint and the distal edge of the trapezium (MC2-axis). RESULTS:
      The FPL does not follow the angle of the thumb metacarpal. The FPL runs ulnarly
      from the MC1-axis at a median of 32.5 degrees  in abduction and 30.6 degrees  in
      adduction. In relation to the MC2-axis, it runs at a median of 47.5 degrees  in
      abduction and 25 degrees  in adduction. CONCLUSIONS: The FPL tendon path can be
      preoperatively marked using: (1) the MC1-axis from which it runs ulnarly
      approximately at an angle of 30 degrees  in both abduction and adduction; or (2)
      the MC2-axis from which it runs radially at an angle of 47.5 degrees  in
      abduction and at an angle of 25 degrees  in adduction. We conclude that the FPL
      tendon path can be preoperatively marked using these axes and does not parallel
      the metacarpal axes of the thumb.

PMID- 30205720
TI  - From darkness to light-Robert J Lifton's the climate swerve - understanding human
      nature to avert global catastrophe.

PMID- 30205721
TI  - Towards feedback-controlled nanomedicines for smart, adaptive delivery.
AB  - Nanomedicines for controlled drug release provide temporal and spatial regulation
      of drug bioavailability in the body. The timing of drug release is usually
      engineered either for slow gradual release over an extended period of time or for
      rapid release triggered by a specific change in its physicochemical environment.
      However, between these two extremes, there is the desirable possibility of
      adaptive nanomedicines that dynamically modulate drug release in tune with its
      changing environment. Adaptation and response through communication with its
      environment is a fundamental trait of living systems; therefore, the design of
      biomimetic nanomedicines through the approaches of bottom-up synthetic biology
      provides a viable route to this goal. This could enable drug delivery systems to
      optimize release in synchronicity with the body's natural biological rhythms and
      the personalized physiological characteristics of the patient, e.g. their
      metabolic rate. Living systems achieve this responsiveness through feedback
      controlled biochemical processes that regulate their functional outputs. Towards
      this goal of adaptive drug delivery systems, we review the general benefits of
      nanomedicine formulations, provide existing examples of experimental
      nanomedicines that encapsulate the metabolic function of enzymes, and give
      relevant examples of feedback-controlled chemical systems. These are the
      underpinning concepts that hold promise to be combined to form novel adaptive
      release systems. Furthermore, we motivate the advantages of adaptive release
      through chronobiological examples. By providing a brief review of these topics
      and an assessment of the state of the art, we aim to provide a useful resource to
      accelerate developments in this field. Impact statement The timing and rate of
      release of pharmaceuticals from advanced drug delivery systems is an important
      property that has received considerable attention in the scientific literature.
      Broadly, these mostly fall into two classes: controlled release with a prolonged
      release rate or triggered release where the drug is rapidly released in response
      to an environmental stimulus. This review aims to highlight the potential for
      developing adaptive release systems that more subtlety modulate the drug release
      profile through continuous communication with its environment facilitated through
      feedback control. By reviewing the key elements of this approach in one place
      (fundamental principles of nanomedicine, enzymatic nanoreactors for medical
      therapies and feedback-controlled chemical systems) and providing additional
      motivating case studies in the context of chronobiology, we hope to inspire
      innovative development of novel "chrononanomedicines."

PMID- 30205722
TI  - Feature Article: Selective modulation of tonically active GABAA receptor
      functional subgroups by G-proteins and protein kinase C.
AB  - IMPACT STATEMENT: Here we study intracellular mechanisms which regulate
      inhibitory signaling delivered through continuously (tonically) open ionotropic
      receptors of gamma-aminobutyric acid (GABA) of dentate gyrus granule cells
      (DGCs). We found that, apart of classical GABA-A receptors (GABAARs) which can be
      activated by GABA binding, a significant part of tonic inhibitory current is
      delivered by newly discovered spontaneously opening GABAARs (s-GABAARs), which
      enter active state without binding of GABA. We have also found that conventional
      GABAARs and s-GABAARs are regulated by different intracellular mechanisms, which
      may overlap and thus induce various signaling repercussions. Our results
      demonstrate that s-GABAARs play a key role in the mechanism that implements DGCs
      functional role in the brain. On top of that, since regulatory mechanisms under
      study are affected in a number of pathological states, our results may have broad
      implications for treatment of neurological disorders.

PMID- 30205724
TI  - Applying a Strengths-Based Psychoeducational Model of Rehabilitation to the
      Treatment of Intimate Partner Violence: Program Theory and Logic Model.
AB  - In the United Kingdom, there is an increasing need to develop prevention programs
      for intimate partner violence and abuse (IPVA). However, this need has increased
      within a context of increasing financial pressure. Consequently, commissioners
      are expressing interest in models of prevention that are brief. This article
      first reviews the effectiveness of domestic violence (DV) prevention programs,
      including those from England and Wales. This article then describes the
      theoretical development of an emerging IPVA prevention program that combines
      solution-focused brief therapy (SFBT) and cognitive behavioral therapy (CBT)
      methods. The article addresses how CBT content is integrated within the SFBT
      approach and provides details of the intervention logic model.

PMID- 30205723
TI  - Preventable Severe Thalassemia among Children.
AB  - This retrospective study analyzed 27 children with preventable severe thalassemia
      born to 24 at-risk couples between 1997 and 2017. The couples were categorized
      into two groups: the prenatal diagnosis (PND) group (n = 8) and the non PND group
      (n = 16). In the PND group, following comprehensive counseling on having a fetus
      with thalassemia, six couples decided to continue the pregnancy (n = 6).
      Termination of the two remaining fetuses was excluded as the thalassemia status
      was reported at a gestational age of 24 weeks. In the non PND group, medical
      errors were found in the misdiagnosis of couples as non thalassemia carriers (n =
      4) and not offering PND to couples with known thalassemia carrier status when
      attending the antenatal clinic (ANC) (n = 2). Additionally, parental ignorance
      was found in parents experiencing their own thalassemia, or that of their spouse
      or child (n = 6). The remaining couples (n = 4) with known carrier status either
      directly refused PND or were ineligible for it. A total of five divorces (5/24 =
      20.8%) occurred in the PND (n = 2) and the non PND (n = 3) groups. Knowledge,
      beliefs, religion, experience of thalassemia, as well as the sex of the at-risk
      fetus all influenced parental decisions. Therefore, both medical personnel and
      parents are key in preventing new cases of thalassemia. Parents should be aware
      of the consequences of having children with severe thalassemia, while medical
      personnel should provide accurate carrier detection and PND.

PMID- 30205726
TI  - Compound Heterozygosity for Silent Cap +1570 (T>C) (HBB: c*96T>C), Codon 39 (C>T)
      (HBB: c.118C>T) and the Presence of alphaalphaalphaanti-3.7/alphaalpha in Greece.
      A Case Presentation.
AB  - The rare point mutation Cap +1570 (T>C) (HBB: c*96T>C) has been reported in
      families of Czech, Greek, Turkish and Italian origin. The mutation contributes to
      a reduction of the beta-globin chain synthesis, and in heterozygous carriers, it
      causes a silent phenotype, while in compound heterozygosity with severe beta
      thalassemia (beta-thal) mutations, it leads to a non transfusion dependent beta
      thal intermedia (beta-TI) state. We report a case of compound heterozygosity for
      codon 39 (C>T) (HBB: c.118C>T) and Cap +1570, in addition to the presence of
      alphaalphaalphaanti-3.7/alphaalpha.

PMID- 30205725
TI  - KFL1 Gene Variants in alpha-Thalassemia Individuals with Increased Fetal
      Hemoglobin in a Chinese Population.
AB  - Kruppel-like factor 1 (KLF1) is a pleiotropic erythroid transcription factor that
      is a regulator of definitive erythropoiesis. The aim of this study was to detect
      KLF1 gene variants in alpha-thalassemia (alpha-thal) carriers with an increased
      Hb F level in a Chinese population, and determine the changes of hematological
      parameters as a result of interactions between KLF1 gene mutations and alpha
      thal. Subjects with alpha-thal and Hb F levels of >=1.0% were selected for
      further investigation. Direct sequencing was used to detect KLF1 gene mutations.
      Hematological parameters of subjects with alpha-thal and concomitant KLF1 gene
      mutations and those with alpha-thal alone were compared. The KLF1 gene variants
      were detected in 46 of 275 (16.7%) individuals with alpha-thal and Hb F levels of
      >=1.0%. The detection rate of KLF1 gene mutations rose correspondingly when the
      Hb F level increased. For alpha0-thal carriers, significantly lower mean
      corpuscular volume (MCV) and mean corpuscular hemoglobin (Hb) (MCH) values were
      observed in KLF1 gene mutation-positive carriers than that in KLF1 gene mutation
      free carriers; conversely, significantly higher Hb A2 and Hb F levels were
      observed in the former condition rather than in the latter condition. The results
      of this study indicate that KLF1 gene variants are common in Chinese subjects
      with alpha-thal and increased Hb F levels, and KLF1 gene mutations decreased the
      red blood cell (RBC) indices in alpha-thal carriers as that in normal adults.

PMID- 30205727
TI  - The Woven EndoBridge (WEB) for recurrent aneurysms: Clinical and imaging results.
AB  - Introduction The Woven EndoBridge (WEB) device is a novel intrasaccular flow
      disrupter designed for wide-necked aneurysms. We present our results of WEB
      treatment in previously treated and reopened aneurysms. Materials and methods
      Between February 2015 and December 2017, 17 patients with reopening of previously
      treated aneurysms were treated using the WEB device. Initial treatment was
      clipping in one, WEB in five and coiling in 11 aneurysms. Six aneurysms had two
      or three previous treatments. Mechanism of aneurysm reopening was clip remnant in
      one, compaction without regrowth in three, focal regrowth in five, reopening in
      partially thrombosed aneurysms in three and WEB compression in five aneurysms.
      Results Endovascular treatment of the recurrent aneurysm was possible in all 17
      patients with good WEB position obtained. Additional devices were used in three
      of 17 patients (18%): coils in two and stent in one patient.  No technical,
      hemorrhagic or thromboembolic complications occurred (0%, 97.5% confidence
      interval 0-22%). Overall imaging result at latest follow-up was complete
      occlusion in five (29%), neck remnant in six (35%), aneurysm reopening in six
      (35%) and persistent WEB filling in one aneurysm (6%). After retreatment with the
      WEB, two aneurysms were again additionally treated and three aneurysms are
      scheduled for additional treatment. Worst results were in partially thrombosed
      aneurysms. Conclusion The WEB device for recurrent aneurysms may be a feasible
      and safe option, especially in wide-necked, shallow aneurysm recurrences. Results
      were poor in partially thrombosed recurrent aneurysms.

PMID- 30205728
TI  - Mechanical thrombectomy utilising a collateral pathway in a patient with
      dysgenesis of the internal carotid artery.
AB  - We describe a case of acute middle cerebral artery occlusion in a patient with
      ipsilateral internal carotid artery dysgenesis successfully treated with
      mechanical thrombectomy utilising a collateral pathway. During the procedure, a
      triaxial system using a balloon guiding catheter, flexible large lumen aspiration
      catheter and stent retriever was advanced from the left vertebral artery to the
      occluded left middle cerebral artery through the left posterior communicating
      artery. Because proximal aspiration from the balloon guiding catheter alone might
      have insufficient suction force due to the retrograde blood flow from large
      vascular communications (e.g. vertebral artery union), the tip of the flexible
      large lumen aspiration catheter was set at the proximal left middle cerebral
      artery, and distal aspiration was added during stent retrieval. A thrombolysis in
      cerebral infarction 2b result was achieved after the first pass. In this case,
      identification of carotid canal hypoplasia on computed tomography allowed for an
      immediate attempt of this alternative approach, avoiding a delay in the time to
      reperfusion.

PMID- 30205729
TI  - HMGB1 represses the anti-cancer activity of sunitinib by governing TP53
      autophagic degradation via its nucleus-to-cytoplasm transport.
AB  - Sunitinib, a multikinase inhibitor approved for a number of cancer indications
      has a low response rate. Identifying mechanisms of resistance could lead to
      rational combination regimens that could improve clinical outcomes. Here we
      report that resistance to sunitinib therapy was driven by autophagic degradation
      of TP53/p53. Deletion of ATG7 or ATG5 suppressed TP53 degradation, as did
      knockdown of SQSTM1/p62. Mechanistically, the transport of TP53 from the nucleus
      to the cytoplasm was essential for the sunitinib-induced autophagic degradation
      of TP53 and did not require TP53 nuclear export signals (NESs). Moreover, TP53
      degradation was achieved by the transport of its nuclear binding target, HMGB1,
      which shifted TP53 from the nucleus to the cytoplasm. The inhibition of HMGB1
      sensitized cancer cells to sunitinib. Importantly, sunitinib induced the
      degradation of all TP53 proteins, except for TP53 proteins with mutations in the
      interaction domain of TP53 with HMGB1 (amino acids 313 to 352). In conclusion,
      our data identify an alternative HMGB1-mediated TP53 protein turnover mechanism
      that participates in the resistance of sunitinib and suggest HMGB1 as a potential
      therapeutic target for improving clinical outcomes of sunitinib.

PMID- 30205730
TI  - Multimodality Monitoring in Neurocritical Care: Decision-Making Utilizing Direct
      And Indirect Surrogate Markers.
AB  - Substantial progress has been made to create innovative technology that can
      monitor the different physiological characteristics that precede the onset of
      secondary brain injury, with the ultimate goal of intervening prior to the onset
      of irreversible neurological damage. One of the goals of neurocritical care is to
      recognize and preemptively manage secondary neurological injury by analyzing
      physiologic markers of ischemia and brain injury prior to the development of
      irreversible damage. This is helpful in a multitude of neurological conditions,
      whereby secondary neurological injury could present including but not limited to
      traumatic intracranial hemorrhage and, specifically, subarachnoid hemorrhage,
      which has the potential of progressing to delayed cerebral ischemia and
      monitoring postneurosurgical interventions. In this study, we examine the
      utilization of direct and indirect surrogate physiologic markers of ongoing
      neurologic injury, including intracranial pressure, cerebral blood flow, and
      brain metabolism.

PMID- 30205731
TI  - Data Abstraction Error in Systematic Review of Global Longitudinal Strain Using
      Speckle-Tracking Echocardiography as a Mortality Predictor in Sepsis.

PMID- 30205732
TI  - Posterior interosseous artery pedicle flap: an anatomical study of the
      relationship between the posterior interosseous nerve and artery.
AB  - The anatomical relationships of the posterior interosseous artery and nerve are
      not well described. To characterize these relationships, ten cadaveric forearms
      were dissected and the relationships between the posterior interosseous nerve,
      its branches, and the posterior interosseous artery documented. The dissection of
      the posterior interosseous artery flap can be conceptualized in three zones with
      decreasing risk to the nerve as the dissection proceeds from proximal to distal.
      Provided fine motor branches of the posterior interosseous nerve are protected
      during the dissection of the nerve and artery, this flap can be harvested with
      safety.

PMID- 30205733
TI  - The Demise of the Absorb BVS: Lessons Learned From the Discontinuation of a
      Disappearing Stent.

PMID- 30205734
TI  - Predictors of Alcohol Use Disorders Among Baby Boomers Across the Life Course.
AB  - Research suggests that baby boomers entering older adulthood may possess unique
      alcohol use patterns over time. Using the life course perspective as a guiding
      framework, this empirical study sought to examine correlates of alcohol use
      disorders among baby boomers by examining representative data from the National
      Survey on Drug Use and Health at two points in time, 1998 ( N = 6,213) and 2010 (
      N = 5,880). Results from logistic regression analyses suggest that predictors of
      alcohol use disorders evolve over time as baby boomers continue to age. Risk
      factors for alcohol use disorders among baby boomers may include concurrent
      unprescribed pain reliever use, p < .01, while protective factors such as income,
      p < .01, and social supports, p = .01, may be of increased importance. Based on
      the findings of this study, practice implications and future research are
      discussed.

PMID- 30205735
TI  - CERKL regulates autophagy via the NAD-dependent deacetylase SIRT1.
AB  - Macroautophagy/autophagy is an important intracellular mechanism for the
      maintenance of cellular homeostasis. Here we show that the CERKL (ceramide kinase
      like) gene, a retinal degeneration (RD) pathogenic gene, plays a critical role in
      regulating autophagy by stabilizing SIRT1. In vitro and in vivo, suppressing
      CERKL results in impaired autophagy. SIRT1 is one of the main regulators of
      acetylation/deacetylation in autophagy. In CERKL-depleted retinas and cells,
      SIRT1 is downregulated. ATG5 and ATG7, 2 essential components of autophagy, show
      a higher degree of acetylation in CERKL-depleted cells. Overexpression of SIRT1
      rescues autophagy in CERKL-depleted cells, whereas CERKL loses its function of
      regulating autophagy in SIRT1-depleted cells, and overexpression of CERKL
      upregulates SIRT1. Finally, we show that CERKL directly interacts with SIRT1, and
      may regulate its phosphorylation at Ser27 to stabilize SIRT1. These results show
      that CERKL is an important regulator of autophagy and it plays this role by
      stabilizing the deacetylase SIRT1.

PMID- 30205736
TI  - Three-Year Results of the Absorb Everolimus-Eluting Bioresorbable Vascular
      Scaffold in Infrapopliteal Arteries.
AB  - PURPOSE: To investigate the midterm performance of the everolimus-eluting Absorb
      bioresorbable vascular scaffold (BVS) for the treatment of symptomatic
      infrapopliteal atherosclerotic disease. METHODS: A single-center study
      prospectively enrolled 48 symptomatic patients (mean age 82.1+/-8.0 years; 27
      men) between September 2013 and February 2018 to evaluate the Absorb everolimus
      eluting BVS system in distal popliteal and tibial lesions. Mean lesion length was
      20.1+/-10.8 mm. Following predilation, up to 2 BVS were implanted in target
      lesions in 55 limbs. Clinical and duplex ultrasound follow-up was performed at 1,
      3, 6, 12, 24, 36, and 48 months to determine 30-day morbidity and midterm Kaplan
      Meier estimates of binary restenosis, clinically-driven target lesion
      revascularization (CD-TLR), amputation, and mortality. RESULTS: Seventy-one
      scaffolds were implanted to treat 61 lesions. Technical success was achieved in
      all patients, with no amputation, death, or target limb bypass surgery within 30
      days of the index procedure. There was 1 early thrombotic occlusion of 2 BVS in a
      previously anticoagulated patient not given antiplatelet medication after the
      procedure. During a mean follow-up of 24.0+/-15.3 months, 11 (23%) patients died;
      the remaining 37 were available for follow-up. Binary restenosis (50%-75%) was
      detected in 6 (8%) scaffolds. Primary patency estimates at 12, 24, and 36 months
      were 92.2%, 90.3%, and 81.1%; freedom from CD-TLR estimates were 97.2%, 97.2%,
      and 87.3% at the same time points. No late scaffold thrombosis has been observed.
      The majority of the 55 limbs (51, 93%) were clinically improved; 4 (7%) were
      unchanged. Thirty-six (92%) of 39 limbs treated for tissue loss achieved complete
      wound healing, with no major amputation (limb salvage 100%). CONCLUSION: Midterm
      follow-up demonstrates excellent safety, patency, and freedom from CD-TLR rates
      using the Absorb bioresorbable vascular scaffold below the knee.

PMID- 30205737
TI  - Local Overdose Fatality Review Team Recommendations for Overdose Death
      Prevention.
AB  - This study compiled and detailed recommendations from Maryland Local Overdose
      Fatality Review Teams (LOFRTs) to provide state and local health departments with
      innovative strategies to address the worsening opioid epidemic and overdose
      related deaths. LOFRTs consist of jurisdictional multiagency, multidisciplinary
      teams that share data to critically examine drug overdose cases. Goals include
      identification of risk factors and intervention opportunities to inform overdose
      prevention programs and policy. The authors qualitatively analyzed reports from
      Maryland LOFRTs case reviews to categorize outcomes and assess using frequency
      analyses. A total of 9 macro-level categories emerged from the review of
      approximately 361 recommendations from LOFRTs. Most recommendations related to
      Prevention Education, Integrated Care, and Harm Reduction strategies. Overdose
      fatality review is an effective means of understanding the opioid epidemic,
      strengthening coordinated interventions, and informing local and state health
      department overdose prevention strategic planning. Teams have a unique vantage
      point from which to view systems-level gaps and policy issues because of their
      collaborative nature and the quality of data provided by agencies that directly
      served decedents.

PMID- 30205738
TI  - Event Segmentation Deficits in ADHD.
AB  - : Event segmentation is the automatic cognitive process of chunking ongoing
      information into meaningful events. Event segmentation theory (EST) proposes that
      event segmentation is a grouping process fundamental to normal, everyday
      perceptual processing, taking a central role in attention and action control. The
      neurocognitive deficits observed among individuals with ADHD overlap those
      involved in event segmentation, but to date no research has examined event
      segmentation in the context of ADHD. OBJECTIVE: The goal of this study was to
      document the event segmentation deficits of individuals with ADHD. METHOD:
      Seventy-five undergraduates with ADHD and seventy-nine without ADHD performed an
      event segmentation task. RESULTS: Results revealed that undergraduates with ADHD
      identify significantly more large events. CONCLUSION: These findingssuggest
      explicit disturbances in the event model and updating system among those with
      ADHD. Future research directions include further elucidating these deficits with
      more varied stimuli and establishing associations with functional impairments.

PMID- 30205739
TI  - Association of IL10 gene promoter polymorphisms with risks of gastric cancer and
      atrophic gastritis.
AB  - Objective To investigate the association between polymorphisms of the interleukin
      10 ( IL10) gene and risk of gastric cancer (GC) and atrophic gastritis (AG).
      Methods This study enrolled patients with GC, patients with AG and healthy
      control subjects. Demographic data were collected and the IL10 gene -1082A/G, 
      819C/T and -592A/C polymorphisms were genotyped. An enzyme-linked immunosorbent
      assay was performed to detect Helicobacter pylori infection. Results The study
      enrolled 556 participants including 208 in the GC group, 116 in the AG group and
      232 controls (CON group). In a recessive model of the IL10-819C/T polymorphism, a
      significantly decreased risk of GC was found compared with AG and non-cancer
      subjects, respectively (AG->GC: odds ratio OR 0.41; non-cancer->GC: OR 0.57). The
      CC genotype demonstrated a significantly increased risk of AG compared with CON.
      Similar significant results were detected in males and H. pylori-negative
      subgroups. The ACC haplotype was associated with a decreased risk of GC compared
      with AG. The ATC haplotype was associated with a decreased risk of AG compared
      with the CON group, but it was associated with an increased risk of GC compared
      with AG. Conclusion The IL10 gene promoter -819C/T (rs1800871) polymorphism was
      associated with the risk of GC and AG in a Chinese population.

PMID- 30205740
TI  - Filterability of exopolysaccharides solutions from the red microalga Porphyridium
      cruentum by tangential filtration on a polymeric membrane.
AB  - The red microalga Porphyridium cruentum is exploited industrially for its
      exopolysaccharides (EPS) and pigments production. EPS produced by P. cruentum are
      partially released and dissolved into the surrounding environment, they can be
      recovered from the culture medium after removing the cells. This paper presents a
      parametric study of the ultrafiltration of EPS solutions on organic membrane. The
      EPS solutions were produced in conditions representative of an industrial
      production. They were filtered at lab-scale on a flat, PES 50 kDa MWCO membrane
      in a complete recirculation mode of permeate and retentate. Permeate flux
      transmembrane pressure (TMP) curves were established up to the limiting flux for
      the filtration of solutions with various values of concentration in EPS (0.10
      1.06 kg GlcEq m-3), fluid tangential velocity (0.3-1.2 m s-1) and temperature (20
      degrees C and 40 degrees C). The reversible and irreversible parts of fouling
      were evaluated for each experiment and the critical flux was determined for an
      intermediate EPS concentration (0.16 kg GlcEq m-3). The results showed that EPS
      solutions had a strong fouling capacity. When filtering the lowest concentrated
      solution (0.10 kg GlcEq m-3) with moderate fouling conditions, the overall
      fouling resistance was approximately half of the membrane and the share of
      irreversible/reversible fouling was 88% and 12%. However, the part of reversible
      fouling becomes predominant when approaching the limiting flux. Permeate fluxes
      which were obtained allow to estimate that a VRR of approximately 10 could be
      obtained when concentrating EPS solutions using PES membranes in flat or tubular
      modules but not in spiral-wound.

PMID- 30205741
TI  - Molecular dissection of CHARGE syndrome highlights the vulnerability of neural
      crest cells to problems with alternative splicing and other transcription-related
      processes.
AB  - CHARGE syndrome is characterized by co-occurrence of multiple malformations due
      to abnormal development of neural crest cells. Here, we review the phenotypic and
      molecular overlap between CHARGE syndrome and similar pathologies, and further
      discuss the observation that neural crest cells appear especially sensitive to
      malfunction of the chromatin-transcription-splicing molecular hub.

PMID- 30205742
TI  - A different kind of pain: affective valence of errors and incongruence.
AB  - People hiss and swear when they make errors, frown and swear again when they
      encounter conflicting information. Such error- and conflict-related signs of
      negative affect are found even when there is no time pressure or external reward
      and the task itself is very simple. Previous studies, however, provide
      inconsistent evidence regarding the affective consequences of resolved conflicts,
      that is, conflicts that resulted in correct responses. We tested whether response
      accuracy in the Eriksen flanker task will moderate the effect of trial
      incongruence using affective priming to measure positive and negative affect. We
      found that responses to incongruent trials elicit positive affect irrespective of
      their accuracy. Errors, in turn, result in negative affect irrespective of trial
      congruence. The effects of conflicts and errors do not interact and affect
      different dimensions of affective priming. Conflicts change the speed of
      evaluative categorisation while errors are reflected in categorisation accuracy.
      We discuss the findings in light of the "reward value and prediction" model and
      the "affect as a feedback for predictions" framework and consider the possible
      mechanisms behind the divergent effects.

PMID- 30205744
TI  - Investigation on phenol degradation capability of Scenedesmus regularis:
      influence of process parameters.
AB  - Phenol removal from environmental solutions has attracted much attention due to
      phenol's high toxicity, even at low concentrations. This study aims to reveal the
      phenol biodegradation capacity of Scenedesmus regularis. Batch system parameters
      (pH, amount of algal cell, phenol concentration) on biodegradation were examined.
      After 24 h of treatment, 92.16, 94.50, 96.20, 80.53, 65.32, 52 and 40% of phenol
      were removed by Scenedesmus regularis in aqueous solutions containing 5, 10, 15,
      20, 30, 40 and 50 mg/L of phenol, respectively. To describe the correlation
      between degradation rate and phenol concentration, the Michaelis-Menten kinetic
      equation was used where Vmax and Km are 0.82 mg phenol g algea-1 h-1 and 24.97
      ppm, respectively. Phenol remediation ability of S.regularis can enable the usage
      of the spent biomass as biofuel feedstock and animal feed makes it a 'green'
      environmental sustainable process.

PMID- 30205743
TI  - Pneumonia in patients with systemic lupus erythematosus: Epidemiology,
      microbiology and outcomes.
AB  - Background and objective Pneumonia remains the main cause of mortality in
      patients with systemic lupus erythematosus (SLE). The aim of the study was to
      establish the clinical characteristics, microbiology and risk factors for poor
      prognosis in patients with SLE and pneumonia. Methods We reviewed medical records
      of patients with SLE (American College of Rheumatology criteria) and pneumonia
      who attended the emergency room in a single tertiary care center (January 2010
      March 2015). We collected demographics, treatment and disease activity (SLEDAI
      2K) data. Severity scales of pneumonia (CURB-65 (acronym for risk factors
      measured: confusion, urea nitrogen, respiratory rate, blood pressure, 65 years of
      age and older) and Pneumonia Severity Index (PSI)) were obtained. A negative
      composite outcome was defined as need for mechanical ventilation, septic shock or
      death secondary to pneumonia up to 30 days after discharge. We conducted a
      univariate and multivariable analysis. Results We studied 158 patients (76%
      women) with 187 episodes of pneumonia. There were no differences in age, SLE
      duration, SLE activity, treatment or comorbidities between patients with negative
      composite outcome vs the other group. In 53 episodes, patients presented with a
      negative composite outcome. Of these, 46 (24.6%) required intubation, 13 (7%)
      developed shock and 12 (6.4%) died. The most common bacteria isolated was S.
      aureus, and we observed a high percentage of nonhabitual microorganisms. Fifteen
      percent of patients who presented with a negative outcome had low values on CURB
      65 and PSI scales. Conclusion Patients with SLE and pneumonia have a high risk of
      complications and present with a high percentage of nonhabitual microorganisms.
      Severity scales for pneumonia can misclassify as low risk SLE patients with poor
      prognosis.

PMID- 30205745
TI  - A Global Perspective Is Needed to Effectively Protect Environmental and
      Occupational Health and Safety.

PMID- 30205747
TI  - Simultaneous dual-channel imaging to quantify interdependent protein recruitment
      to laser-induced DNA damage sites.
AB  - Fluorescence microscopy in combination with the induction of localized DNA damage
      using focused light beams has played a major role in the study of protein
      recruitment kinetics to DNA damage sites in recent years. Currently published
      methods are dedicated to the study of single fluorophore/single protein kinetics.
      However, these methods may be limited when studying the relative recruitment
      dynamics between two or more proteins due to cell-to-cell variability in gene
      expression and recruitment kinetics, and are not suitable for comparative
      analysis of fast-recruiting proteins. To tackle these limitations, we have
      established a time-lapse fluorescence microscopy method based on simultaneous
      dual-channel acquisition following UV-A-induced local DNA damage coupled with a
      standardized image and recruitment analysis workflow. Simultaneous acquisition is
      achieved by spectrally splitting the emitted light into two light paths, which
      are simultaneously imaged on two halves of the same camera chip. To validate this
      method, we studied the recruitment of poly(ADP-ribose) polymerase 1 (PARP1), poly
      (ADP-ribose) glycohydrolase (PARG), proliferating cell nuclear antigen (PCNA) and
      the chromatin remodeler ALC1. In accordance with the published data based on
      single fluorophore imaging, simultaneous dual-channel imaging revealed that PARP1
      regulates fast recruitment and dissociation of PARG and that in PARP1-depleted
      cells PARG and PCNA are recruited with comparable kinetics. This approach is
      particularly advantageous for analyzing the recruitment sequence of fast
      recruiting proteins such as PARP1 and ALC1, and revealed that PARP1 is recruited
      faster than ALC1. Split-view imaging can be incorporated into any laser
      microirradiation-adapted microscopy setup together with a recruitment-dedicated
      image analysis package.

PMID- 30205746
TI  - Phase 2 Trial of Selective Tyrosine Kinase 2 Inhibition in Psoriasis.
AB  - BACKGROUND: Tyrosine kinase 2 (TYK2) signaling pathways, which mediate cytokine
      signaling, are implicated in the pathophysiology of psoriasis. Selective
      inhibitors of TYK2 may be effective in treating psoriasis. METHODS: We conducted
      a phase 2, double-blind trial of a TYK2 inhibitor, BMS-986165, in adults with
      moderate-to-severe psoriasis, excluding patients with a previous lack of response
      to agents targeting cytokine signaling through the same tyrosine kinase pathway.
      Patients were randomly assigned to receive the drug orally at a dose of 3 mg
      every other day, 3 mg daily, 3 mg twice daily, 6 mg twice daily, or 12 mg daily
      or to receive placebo. The primary end point was a 75% or greater reduction from
      baseline in the Psoriasis Area and Severity Index (PASI) score at week 12 (higher
      scores indicate greater severity of psoriasis). RESULTS: A total of 267 patients
      received at least one dose in an intervention group of the trial. At week 12, the
      percentage of patients with a 75% or greater reduction in the PASI score was 7%
      (3 of 45 patients) with placebo, 9% (4 of 44 patients) with 3 mg of BMS-986165
      every other day (P=0.49 vs. placebo), 39% (17 of 44 patients) with 3 mg daily
      (P<0.001 vs. placebo), 69% (31 of 45 patients) with 3 mg twice daily (P<0.001 vs.
      placebo), 67% (30 of 45 patients) with 6 mg twice daily (P<0.001 vs. placebo),
      and 75% (33 of 44 patients) with 12 mg daily (P<0.001 vs. placebo). There were
      three serious adverse events in patients receiving the active drug, as well as
      one case of malignant melanoma 96 days after the start of treatment. CONCLUSIONS:
      Selective inhibition of TYK2 with the oral agent BMS-986165 at doses of 3 mg
      daily and higher resulted in greater clearing of psoriasis than did placebo over
      a period of 12 weeks. Larger and longer-duration trials of this drug are required
      to determine its safety and durability of effect in patients with psoriasis.
      (Funded by Bristol-Myers Squibb; ClinicalTrials.gov number, NCT02931838 .).

PMID- 30205748
TI  - DNA entry, exit and second DNA capture by cohesin: insights from biochemical
      experiments.
AB  - Cohesin is a ring-shaped, multi-subunit ATPase assembly that is fundamental to
      the spatiotemporal organization of chromosomes. The ring establishes a variety of
      chromosomal structures including sister chromatid cohesion and chromatin loops.
      At the core of the ring is a pair of highly conserved SMC (Structural Maintenance
      of Chromosomes) proteins, which are closed by the flexible kleisin subunit. In
      common with other essential SMC complexes including condensin and the SMC5-6
      complex, cohesin encircles DNA inside its cavity, with the aid of HEAT
      (Huntingtin, elongation factor 3, protein phosphatase 2A and TOR) repeat
      auxiliary proteins. Through this topological embrace, cohesin is thought to
      establish a series of intra- and interchromosomal interactions by tethering more
      than one DNA molecule. Recent progress in biochemical reconstitution of cohesin
      provides molecular insights into how this ring complex topologically binds and
      mediates DNA-DNA interactions. Here, I review these studies and discuss how
      cohesin mediates such chromosome interactions.

PMID- 30205751
TI  - Fistula-tract Laser Closure (FiLaCTM) for complex urethroperineal fistula.
AB  - BACKGROUND: Fistula formation in hidradenitis suppurativa follows an uncontrolled
      infection with subcutaneous tracts leading to 'watering-can' or 'pus-pot'
      perineum. Closure of this type of fistula implies major surgery and is bound to
      fail in refractory inflammatory environment. Minimally invasive techniques have
      become the first line of choice in every type of surgery. METHODS: Fistula-tract
      Laser Closure (FiLaCTM, Biolitec, Germany) is a novel technique already reported
      to have been used in the treatment of fistula-in-ano and pilonidal sinus. It
      consists of blind cauterization and obliteration of the fistula tract from the
      inside by means of a radial-emitting laser probe. We present two patients who
      underwent surgery for urethroperineal fistula using this technique. RESULTS: In
      both cases, the fistula tracts were completely closed after 3 months of follow
      up. The wounds had healed smoothly and complete resolution of symptoms was noted.
      CONCLUSIONS: The use of FiLaCTM for the treatment of urethroperineal fistula is
      feasible and safe. The minimally invasive nature of the technique and limited
      postoperative pain permit daycare surgery.

PMID- 30205749
TI  - Converse Smith-Martin cell cycle kinetics by transformed B lymphocytes.
AB  - Recent studies using direct live cell imaging have reported that individual B
      lymphocytes have correlated transit times between their G1 and S/G2/M phases.
      This finding is in contradiction with the influential model of Smith and Martin
      that assumed the bulk of the total cell cycle time variation arises in the G1
      phase of the cell cycle with little contributed by the S/G2/M phase. Here we
      extend these studies to examine the relation between cell cycle phase lengths in
      two B lymphoma cell lines. We report that transformed B lymphoma cells undergo a
      short G1 period that displays little correlation with the time taken for the
      subsequent S/G2/M phase. Consequently, the bulk of the variation noted for total
      division times within a population is found in the S/G2/M phases and not the G1
      phase. Models that reverse the expected source of variation and assume a single
      deterministic time in G1 followed by a lag + exponential distribution for S/G2/M
      fit the data well. These models can be improved further by adopting two
      sequential distributions or by using the stretched lognormal model developed for
      primary lymphocytes. We propose that shortening of G1 transit times and
      uncoupling from other cell cycle phases may be a hallmark of lymphocyte
      transformation that could serve as an observable phenotypic marker of cancer
      evolution.

PMID- 30205752
TI  - Investigation of the probable homo-dimer model of the Xeroderma pigmentosum
      complementation group A (XPA) protein to represent the DNA binding core.
AB  - The Xeroderma pigmentosum complementation group A (XPA) protein functions as a
      primary damage verifier and as a scaffold protein in nucleotide excision repair
      (NER) in all higher organisms. New evidence of XPA's existence as a dimer and the
      redefinition of its DNA binding domain (DBD) raises new questions regarding the
      stability and functional position of XPA in NER. Here, we have investigated XPA's
      dimeric status with respect to its previously-defined DBD (XPA98-219) as well as
      with its redefined DBD (XPA98-239). We studied the stability of XPA98-210 and
      XPA98-239 homo-dimer systems using all-atom molecular dynamics simulation, and we
      have also characterized the protein-protein interactions (PPI) of these two homo
      dimeric forms of XPA. After conducting the root mean square deviation (RMSD)
      analyses, it was observed that the XPA98-239 homo-dimer has better stability than
      XPA98-210. It was also found that XPA98-239 has a larger number of hydrogen
      bonds, salt bridges, and hydrophobic interactions than the XPA98-210 homo-dimer.
      We further found that Lys, Glu, Gln, Asn and Arg residues shared the major
      contribution toward the intermolecular interactions in XPA homo-dimers. The
      binding free energy (BFE) analysis, which used the molecular mechanics Poisson
      Boltzmann method (MM-PBSA) and the generalized Born and surface area continuum
      solvation model (GBSA) for both XPA homo-dimers, also substantiated the positive
      result in favor of the stability of the XPA98-239 homo-dimer.

PMID- 30205750
TI  - Quality control guidelines for clinical-grade human induced pluripotent stem cell
      lines.
AB  - Use of clinical-grade human induced pluripotent stem cell (iPSC) lines as a
      starting material for the generation of cellular therapeutics requires
      demonstration of comparability of lines derived from different individuals and in
      different facilities. This requires agreement on the critical quality attributes
      of such lines and the assays that should be used. Working from established
      recommendations and guidance from the International Stem Cell Banking Initiative
      for human embryonic stem cell banking, and concentrating on those issues more
      relevant to iPSCs, a series of consensus workshops has made initial
      recommendations on the minimum dataset required to consider an iPSC line of
      clinical grade, which are outlined in this report. Continued evolution of this
      field will likely lead to revision of these guidelines on a regular basis.

PMID- 30205753
TI  - Embracing integration and complexity: placing emotion within a science of brain
      and behaviour.
AB  - The present paper addresses conceptual issues that are central to emotion
      research. What is emotion? What are its defining characteristics? The field
      struggles with questions like these almost constantly. I argue that definitions,
      and deciding what is the proper status of emotion, are not a requirement for
      scientific progress - in fact, they can hinder it. Therefore, "emotion"
      researchers should strive to develop a science of complex behaviours, and worry
      less about their exact nature. But for interesting behaviours, is most of the
      explaining that is needed present at the level of isolated systems (perception,
      cognition, etc.) or at the level of interactions between them? I suggest that the
      level of interactions is where most of the work is needed. Accordingly, I
      advocate that it is important to embrace integration, and not to strive to
      necessarily disentangle the multiple contributions underlying behaviours. More
      generally, it is argued that we need to revise models of causation adopted when
      reasoning about the mind and brain. Instead, a "complex systems" approach is
      required where the interactions between multiple components lead to system-level 
      emergent - properties that cannot be isolated or attributed to more elementary
      parts.

PMID- 30205755
TI  - Health Literacy Among Swedish Lung Transplant Recipients 1 to 5 Years After
      Transplantation.
AB  - INTRODUCTION:: Understanding medical information and self-management ability is
      vital for good quality of life among transplant recipients. However, health
      literacy (HL) has never been investigated among lung transplant recipients.
      OBJECTIVE:: This study investigated HL among Swedish lung transplant recipients 1
      to 5 years after lung transplantation in relation to recovery, fatigue,
      adherence, cognitive function (CF), and relevant demographic variables. METHOD::
      This study was part of a cross-sectional, Swedish multicenter study 1 to 5 years
      post lung transplantation called Self-Management after Thoracic Transplantation.
      In total, 117 (57%) of 204 eligible lung recipients due for their yearly follow
      up were included; 1 year (n = 35), 2 years (n = 28), 3 years (n = 23), 4 years (n
      = 20) or 5 years (n = 11) after transplantation. The newest vital sign (NVS)
      instrument was used to measure the level of HL and contained 6 interview
      questions. The total scores ranged from 0 to 6 with 0 to 1= inadequate/low, 2 to
      3 = marginal, 4 to 6 = adequate/good HL. RESULTS:: Twenty-one percent reported an
      NVS score of 0 to 3 indicating low or marginal HL and 79% scored 4 to 6
      indicating adequate HL. Recipients scoring low or marginal were represented in
      all 5 years posttransplant, and the majority were not able to work. Health
      literacy was not related to age, sex, fatigue, adherence, recovery, marital
      status, or self-reported CF. DISCUSSION:: Health literacy was good among Swedish
      lung recipients. Providers should be aware that patients with low HL might
      present at any time posttransplant, and screening will help identify patients who
      need extra support.

PMID- 30205756
TI  - Global Longitudinal Strain Using Speckle-Tracking Echocardiography in Sepsis.

PMID- 30205757
TI  - Attentional bias to pain-related information: a meta-analysis of dot-probe
      studies.
AB  - Studies investigating attentional biases towards pain information vary widely in
      both design and results. The aim of this meta-analysis was to determine the
      degree to which attentional biases towards pain occur when measured with the dot
      probe task. A total of 2168 references were screened, resulting in a final sample
      of 4466 participants from 52 articles. Participants were grouped according to
      pain experience: chronic pain, acute pain, anticipating experimental/procedural
      pain, social concern for pain, or healthy people. In general, results revealed a
      significant, but small bias towards pain words (d =  0.136), and pain pictures (d
      =  0.110) in chronic pain patients, but not in those with acute pain, those
      anticipating pain, or healthy people. Follow-up analyses revealed an attentional
      bias towards sensory pain words in the chronic pain group (d =  0.198), and the
      acute pain group (d =  0.303), but not other groups. In contrast, attentional
      biases towards affective pain stimuli were not significant for any pain groups.
      This meta-analysis found support for attentional biases towards sensory pain
      stimuli in patients with chronic pain in comparison to healthy individuals across
      a range of common parameters. Future researchers need to consider task design
      when seeking to optimally measure pain-relevant attentional biases.

PMID- 30205759
TI  - The ideal frequency of temperature data collection in compostability experiments
      on domestic organic residues.
AB  - One of the main analytical variable to indicate the evolution and the phases of
      the composting process is temperature, whose constant monitoring is fundamental
      for decision making. However, studies usually perform collection of temperature
      data with a daily frequency due to the operational difficulty in obtaining this
      information from manually collected samples. Thus, the aim of this study was to
      determine the ideal frequency of temperature data collection in composting
      layers. Eight composting layers containing tree prunings + domestic organic
      residues were installed and four temperature sensors were installed in each
      layer. The temperature data were collected and recorded from minute to minute by
      means of a datalogger developed with an Arduino board during 70 days of
      composting. Thus, the collected temperatures were used as a pilot sample, and
      therefore the ideal temperature collection rate was estimated for different
      estimation error limits. No significant difference was found between the
      different collection times according to the Kruskal-Wallis test at a significance
      level of 5%. Therefore, the ideal collection frequency can be determined from the
      error limit of temperature estimation that is acceptable to the researcher.

PMID- 30205758
TI  - Patients From Appalachia Have Reduced Access to Liver Transplantation After Wait
      Listing.
AB  - BACKGROUND:: The Appalachian region is medically underserved and characterized by
      high morbidity and mortality. We investigated disparities among patients listed
      for liver transplantation (LT) in wait-list outcomes, according to residence in
      the Appalachian region. METHODS:: Data on adult patients listed for LT were
      obtained from the United Network for Organ Sharing for July 2013 to December
      2015. Wait-list outcomes were compared using cause-specific hazard models by
      region of residence (Appalachian vs non-Appalachian) among patients listed at
      centers serving Appalachia. Posttransplant patient and graft survival were also
      compared. The study included 1835 LT candidates from Appalachia and 5200 from non
      Appalachian regions, of whom 1016 patients experienced wait-list mortality or
      were delisted; 3505 received liver transplants. RESULTS:: In multivariable
      analyses, patients from Appalachia were less likely to receive LT (hazard ratio
      [HR] = 0.86; 95% confidence interval [CI]: 0.79-0.93; P < .001), but Appalachian
      residence was not associated with wait-list mortality or delisting (HR = 1.03;
      95% CI: 0.89-1.18; P = .696). Among liver transplant recipients, patient and
      graft survival did not differ by Appalachian versus non-Appalachian residence.
      CONCLUSION:: Appalachian residence was associated with lower access to
      transplantation after listing for LT. This geographic disparity should be
      addressed in the current debate over reforming donor liver allocation and patient
      priority for LT.

PMID- 30205760
TI  - Information, Motivation, and Self-Efficacy Among Men Who Have Sex With Men and
      Transgender Women in the State of Maharashtra, India.
AB  - BACKGROUND: India's National AIDS Control Programme calls for, among other
      things, targeted behavioral interventions that address determinants contributing
      to new infections among men who have sex with men (MSM) and hijras (transgender
      women). AIM: To determine if the information-motivation-behavioral skills model
      was transferable to an Indian context. METHODS: We recruited 442 MSM and 7 hijras
      into an online cross-sectional study that asked questions about condom use
      knowledge, motivation, self-efficacy, and sexual behavior. Structural equation
      modeling was used to test the overall information-motivation-behavioral skills
      structure. RESULTS: Condom use and HIV risk knowledge did not significantly
      predict condom use self-efficacy or having condomless anal sex with more than one
      male partner in the past 3 months, and knowledge was not significantly correlated
      with attitudes toward barebacking. Despite this, the final structural model
      explained 14.4% of the variance in condom use self-efficacy and 20.0% of the
      variance in risky sexual behavior. Overall fit of the model was good: chi2(201, N
      = 447) = 445.002, p < .0001, root mean square error of approximation = .052, 90%
      CI [.046, .059], comparative fit index = .989, Tucker-Lewis Index = .987.
      CONCLUSION: The public health response to India's HIV epidemic is currently
      different than in the West due to differences in medication access and public
      health infrastructure. As Indian MSM and hijras learn more about the
      effectiveness of viral suppression and hopefully have greater access to
      preexposure prophylaxis, researchers should monitor for changing attitudes toward
      condoms and be prepared to collaborate with the public health infrastructure in
      order to develop interventions that reinforce positive attitudes toward condom
      use.

PMID- 30205761
TI  - Occupational Therapists' Interactions With Older Adult Caregivers: Negotiating
      Priorities and Expertise.
AB  - Although numerous studies have examined provider-caregiver interactions and their
      influence on care outcomes, few represent the perspective of the provider or
      specifically consider occupational therapy practitioners. The aim of this article
      is to explore the perspectives of occupational therapists regarding interactions
      with older adult caregivers in geriatric practice settings. The study was
      conducted using a constructivist grounded theory approach based on data obtained
      from repeated focus group sessions and subsequent individual reflections.
      Occupational therapy practitioners interact with older adult caregivers in ways
      that reflect negotiations about who holds expertise and whose priorities are most
      relevant in care situations. These interactions are influenced by health care
      contexts that foreground the needs of the care recipient. A deeper understanding
      of caregiving as an occupation via a transactional perspective may serve to
      illuminate complex care situations and optimize therapist-caregiver interactions.

PMID- 30205762
TI  - Energy Balance Coexists With Disproportionate Macronutrient Consumption Across
      Pretraining, During Training, and Posttraining Among Indian Junior Soccer
      Players.
AB  - PURPOSE: To evaluate energy expenditure, energy intake, and nutrient adequacy of
      Indian junior soccer players. METHOD: Forty junior national-level soccer players
      (Under-12 and Under-16 age groups) were assessed for 3-day weighed food records
      and 3-day energy expenditure. Energy and nutrient intake was analyzed from food
      records, and energy expenditure was measured using a portable metabolic analyzer
      and activity records. Nutrient adequacy was determined by comparing intake with
      prevailing recommendations. RESULTS: Players exhibited no significant difference
      between energy intake (boys = 3062 [340.9] and girls = 2243 [320.3] kcal.d-1) and
      expenditure (boys = 2875 [717.3] and girls = 2442 [350.3] kcal.d-1). Across age
      groups, the Under-12 boys showed positive energy balance as against energy
      deficits in Under-16. Girls showed energy deficits, although not significant.
      There were 58% of girls showing energy availability <30 kcal.kg-1 fat-free mass,
      of which 37% were Under-16 players. Carbohydrates contributed to >60% of energy
      expenditure among 95.2% boys and 73.7% girls. Among 52.4% boys and 47.4% girls,
      <25% of energy expenditure was contributed by fat. More than 95% players consumed
      <1 g.kg-1 carbohydrates pretraining and 100% of them consumed >1.2 g.kg-1
      carbohydrates posttraining. CONCLUSION: Junior soccer players consumed more than
      recommended carbohydrates in the diet, although not aligning with the
      pretraining, during training, and posttraining meal requirements. Considering the
      energy deficits observed among Under-16 players, a suitable dietary modification
      is warranted.

PMID- 30205763
TI  - Investigating the role of internal layout of magnetic field-generating equipment
      on workers' exposure at power substations.
AB  - INTRODUCTION: This research is an attempt to show the role of interior layout of
      equipment in generating magnetic fields. MATERIALS AND METHODS: The levels of an
      extremely low-frequency magnetic field were measured in accordance with Standard
      No. IEEE 644:1994 in three substations and a control building in a petrochemical
      power plant in southern Iran. Then, workers' occupational exposure (time-weighted
      average [TWA]) was calculated and the sources of maximum magnetic field
      generation at each place were identified. Their interior design was changed to
      achieve the optimal layout of equipment subsequently; the workers' TWA was
      recalculated for the new situation. RESULTS: The obtained results showed that
      electrical engineers and technicians were exposed to the maximum TWA of 10.14
      MUT. The operators in the control room were exposed to the lowest TWA of 0.84
      MUT. The results also showed that after the change of interior design and proper
      layout design of the equipment in the substations, the TWA was reduced by 0.73
      MUT. CONCLUSION: The research findings revealed that the most harmonious
      arrangement of equipment in an industrial unit plays a major role in reducing the
      exposure of workers to magnetic fields and ultimately increases the level of
      their health in the workplace.

PMID- 30205764
TI  - Antiphospholipid syndrome - an update.
AB  - Antiphospholipid syndrome (APS) is an autoantibody-mediated acquired
      thrombophilia. It is characterized by the presence of antiphospholipid antibodies
      (APL) that are directed against phospholipid-binding plasma proteins, such as
      beta-2-glycoprotein I (b2GPI). Its main manifestations are recurrent vascular
      thromboses (so-called "thrombotic APS") and pregnancy complications ("obstetric
      APS"). According to the current consensus criteria, a persistently positive
      functional lupus anticoagulant (LA) assay and/or the presence of anti-b2GPI
      and/or anti-cardiolipin antibodies, together with clinical symptoms, is mandatory
      for the diagnosis of APS. Other clinical features, such as thrombocytopenia,
      Coombs-positive haemolytic anaemia, heart valve disease, renal microangiopathy
      and neurologic disorders are also common in APL-positive patients. APS can be
      associated with other autoimmune disorders, such as systemic lupus erythematosus.
      In rare cases, catastrophic APS (CAPS) occurs, with the development of excessive
      thrombosis at multiple sites, usually affecting small vessels and leading to
      multi-organ dysfunction and organ failure. Treatment usually comprises
      antithrombotic therapy using antiplatelet and anticoagulant agents. However,
      there is no consensus concerning the intensity or duration of therapy. Despite
      apparently adequate anticoagulation, the risk of recurrent thrombosis remains
      high. For patients with CAPS, a combined therapeutic approach that includes
      anticoagulation, glucocorticoids, plasma exchange and/or intravenous
      immunoglobulin seems to be the best treatment option. Keywords: Antiphospholipid
      syndrome, lupus anticoagulants, anti-cardiolipin, anti-beta-2-glycoprotein I,
      vascular thrombosis, pregnancy complication.

PMID- 30205765
TI  - The association between musculoskeletal disorders and driver behaviors among
      professional drivers in China.
AB  - The main objective of this study is to explore correlations between the severity
      of musculoskeletal disorders (MSDs) and aberrant driving behaviors among
      professional taxi drivers. Questionnaires were administered to 162 taxi drivers
      in a Chinese city. Drivers with more severe MSDs reported more general and
      dangerous error behaviors and negative moods. Interestingly, MSDs affect drivers'
      error behaviors through negative moods. The study also examined the effects of
      age, driving experience, traffic accidents, mood states, safety awareness and
      driving skills on aberrant driving behaviors. The results showed that age and
      driving experience were significant predictors of aberrant driving behaviors.
      Anger was a significant predictor of aggressive violations and dangerous errors.
      Additionally, drivers who reported higher levels of safety awareness also
      reported fewer aggressive violations, and drivers with higher levels of driving
      skills reported fewer dangerous error behaviors.

PMID- 30205766
TI  - Utility of Serum miR-122, Liver Enzymes, and Hepatic Histopathology in Response
      to Hepatotoxicants in Sprague-Dawley Rats.
AB  - More than 80,000 chemicals are in commercial use worldwide. Hepatic metabolism to
      toxic intermediates is often a key mechanism leading to tissue damage and organ
      dysfunction. Effective treatment requires prompt detection of hepatotoxicity,
      ideally with rapid, minimally invasive diagnostic assays. In this study,
      archetypal histologic features of chemically induced hepatic injury were compared
      with clinical chemistries (including liver enzymes) and serum concentrations of
      microRNA-122 (miR-122, the processed form miR-122-5p), a biomarker of liver
      injury. The hepatotoxicants 4,4'-methylenedianiline (4,4'-MDA), allyl alcohol
      (AA), or carbon tetrachloride (CCl4) were orally administered to male Sprague
      Dawley rats for 1, 5, 14, or 28 days to induce liver damage. Formalin-fixed,
      paraffin-embedded liver sections were evaluated histologically for inflammation,
      fibrosis, necrosis, and lipid accumulation. Liver enzymes were measured in serum,
      and serum miR-122 concentrations were assessed by quantitative polymerase chain
      reaction (qPCR). Histologic features of hepatic injury dose-dependently increased
      in both severity and frequency. Increases in liver enzymes and bilirubin were
      more pronounced in response to AA or 4,4'-MDA than to CCl4 at early time points.
      Elevated serum miR-122 levels in animals administered CCl4, AA, or 4,4'-MDA were
      more strongly associated with degree of hepatic histopathology than with dosage.
      Given this sensitive expression pattern postexposure, liver-specific miR-122 may
      improve the diagnostic accuracy of early hepatic injury.

PMID- 30205767
TI  - Integrating Sexual Assault Resistance, Bystander, and Men's Social Norms
      Strategies to Prevent Sexual Violence on College Campuses: A Call to Action.
AB  - Sexual assault prevention on college campuses often includes programming directed
      at men, women, and all students as potential bystanders. Problematically,
      specific types of sexual assault prevention are often implemented on campuses in
      isolation, and sexual assault risk reduction and resistance education programs
      for women are rarely integrated with other approaches. With increasing focus on
      the problem of sexual assault on college campuses, it is timely to envision a
      comprehensive and interconnected prevention approach. Implementing comprehensive
      prevention packages that draw upon the strengths of existing approaches is
      necessary to move toward the common goal of making college campuses safer for all
      students. Toward this goal, this commentary unpacks the models and mechanisms on
      which current college sexual assault prevention strategies are based with the
      goal of examining the ways that they can better intersect. The authors conclude
      with suggestions for envisioning a more synthesized approach to campus sexual
      assault prevention, which includes integrated administration of programs for
      women, men, and all students as potential bystanders on college campuses.

PMID- 30205770
TI  - Alchemical Patronage and the Making of an Adept: Letters of Michael Sendivogius
      to Emperor Rudolf II and His Chamberlain Hans Popp.
AB  - Based on four extant letters the famous Polish alchemist Michael Sendivogius
      wrote to Emperor Rudolf II and his first chamberlain Hans Popp between 1597 and
      1602, this paper adds to a growing body of revisionist scholarship on alchemy in
      Rudolfine Prague. Unlike most of his many rivals - including luminaries such as
      John Dee and Michael Maier - who hoped for the Emperor's patronage in vain,
      Sendivogius officially became a courtier at the imperial court in 1594. As such
      he was in the privileged position of having access to the Emperor and his close
      advisors. The surviving correspondence shows how the Pole successfully balanced
      his alchemical promises against Rudolf's expectations for a number of years. The
      fact that even Sendivogius found it difficult to translate imperial patronage
      into ready money suggests that Emperor Rudolf II was considerably more
      circumspect and less gullible than the widespread cliche suggests. Fully
      contextualised by all available sources on Sendivogius' early career, the four
      letters emerge as important documents regarding the Polish adept and alchemical
      patronage in Rudolfine Prague. They also shed new light on the circumstances
      which led to the writing and publication of Sendivogius' famous treatise De
      lapide philosophorum (Novum lumen chymicum).

PMID- 30205771
TI  - First-Line Therapies for Metastatic Lung Adenocarcinoma Without a Driver
      Mutation.
AB  - Lung cancer is the leading cause of cancer-related death worldwide. The majority
      of these cancers are non-small-cell lung cancer, of which adenocarcinoma is the
      most common histologic subtype. Most patients are diagnosed at advanced stages
      when systemic treatment is needed. Whereas prognosis has improved for patients
      with targetable driver mutations, the majority of patients do not possess tumors
      with such molecular mutations. Platinum-based chemotherapy has traditionally been
      the mainstay of treatment, although in recent years immunotherapy has emerged as
      a treatment option and can result in robust and durable treatment responses in a
      subset of patients. Recent clinical trials on novel immunotherapy combinations
      and immunochemotherapy combinations may broaden the number of patients that may
      benefit from checkpoint inhibitors and elicit responses in those who otherwise
      may not have experienced a response to monotherapy with an immunotherapy drug.
      This review will outline the currently available therapies for the first-line
      treatment of metastatic adenocarcinoma that do not possess a driver mutation and
      provide a recommended approach and algorithm by which to select the best first
      line therapy.

PMID- 30205768
TI  - Measuring the Impact of Tinnitus on Aided Listening Effort Using Pupillary
      Response.
AB  - Tinnitus can have serious impact on a person's life and is a common auditory
      symptom that is especially comorbid with hearing loss. This study investigated
      processing effort required for speech recognition in a group of hearing-impaired
      people with tinnitus and a control group (CG) of hearing-impaired people without
      tinnitus by means of pupillary response. Furthermore, the relationship between
      the pupillary response, self-rating measures of tinnitus severity, and fatigue
      was examined. Participants performed a speech-in-noise task with a competing four
      talker babble at two speech intelligibility levels (50% and 95%) with either an
      active or inactive noise-reduction scheme while the pupillary response was
      recorded. Tinnitus participants showed significantly smaller time-dependent pupil
      dilations and significantly higher fatigue ratings. No correlation was found for
      the tinnitus severity and pupillary response, but a significant correlation was
      found between the tinnitus severity and fatigue. As participants with tinnitus
      generally reported higher fatigue and showed smaller task-evoked pupil dilations,
      it was speculated that this may suggest an increased activity of the
      parasympathetic nervous system, which governs the bodily response during rest.
      The finding that tinnitus participants showed higher fatigue has clinical
      implications, highlighting the importance of taking steps to decrease the risk of
      developing long-term fatigue. Finally, the tinnitus participants showed reduced
      pupillary responses when noise reduction was activated, suggesting a reduced
      effort from hearing aid signal processing.

PMID- 30205772
TI  - Early-Stage Oral Cavity and Oropharyngeal Carcinoma in the Elderly: An Evolving
      Proposition.

PMID- 30205773
TI  - Treatment of Advanced Non-Small-Cell Lung Cancer: From Chemotherapy to
      Chemoimmunotherapy.

PMID- 30205774
TI  - Navigating Through New, First-Line Treatment Options for Lung Cancer.

PMID- 30205775
TI  - Medical Marijuana Use in a Community Cancer Center.
AB  - PURPOSE: The primary purpose of this study was to compare the incidence of
      marijuana use between patients with early- versus advanced-stage cancers.
      Differences in adverse effects, drug-drug interactions, and drug-disease
      interactions between those who use marijuana and those who do not were also
      compared. METHODS: Patients age 18 years and older who were receiving
      chemotherapy were asked to complete an electronic self-reported questionnaire. In
      addition to questions about patient demographics, current adverse effects, cancer
      type and stage, comorbidities, performance status, treatment regimen, and general
      marijuana use, those patients who used marijuana within the last 30 days (current
      marijuana users) were asked additional questions about the route and frequency of
      marijuana administration, about reason(s) for use, about possession of a
      marijuana card, and if they had received any counseling about marijuana. Drug
      drug and drug-disease interactions were also analyzed. RESULTS: The overall
      incidence of marijuana use was 18.3% (32 of 175 patients). The incidence of
      marijuana use in patients with early- versus advanced-stage cancers was 19.6% (11
      of 56 patients) versus 17.6% (21 of 119 patients; P = .75). Patients who use
      marijuana reported more pain, nausea, appetite issues, and anxiety. There were
      more drug-drug interactions associated with marijuana use, primarily with
      concurrent CNS depressants. The frequency of drug-disease interactions between
      those who use marijuana versus those who do not was similar. CONCLUSION:
      Approximately one in five patients with cancer who were receiving chemotherapy
      were using marijuana, and the frequency was equal in early- and advanced-stage
      cancer groups. The risks versus benefits should be discussed with all patients
      who use marijuana.

PMID- 30205776
TI  - Head and Neck Cancer in Elderly Patients: What to Do When Data Are Limited?

PMID- 30205777
TI  - Insights From Pupil Size to Mental Workload of Surgical Residents: Feasibility of
      an Educational Computer-Based Surgical Simulation Environment (ECE) Considering
      the Hand Condition.
AB  - The advantage of simulation environments is that they present various insights
      into real situations, where experimental research opportunities are very limited
      for example, in endoscopic surgery. These operations require simultaneous use of
      both hands. For this reason, surgical residents need to develop several motor
      skills, such as eye-hand coordination and left-right hand coordination. While
      performing these tasks, the hand condition (dominant, nondominant, both hands)
      creates different degrees of mental workload, which can be assessed through
      mental physiological measures-namely, pupil size. Studies show that pupil size
      grows in direct proportion to mental workload. However, in the literature, there
      are very limited studies exploring this workload through the pupil sizes of the
      surgical residents under different hand conditions. Therefore, in this study, we
      present a computer-based simulation of a surgical task using eye-tracking
      technology to better understand the influence of the hand condition on the
      performance of skill-based surgical tasks in a computer-based simulated
      environment. The results show that under the both-hand condition, the pupil size
      of the surgical residents is larger than the one under the dominant and
      nondominant hand conditions. This indicates that when the computer-simulated
      surgical task is performed with both hands, it is considered more difficult than
      in the dominant and nondominant hand conditions. In conclusion, this study shows
      that pupil size measurements are sufficiently feasible to estimate the mental
      workload of the participants while performing surgical tasks. The results of this
      study can be used as a guide by instructional system designers of skill-based
      training programs.

PMID- 30205778
TI  - Assessing the institutional learning curve for pararenal aortic repair using the
      fenestrated Anaconda endograft.
AB  - Objective Custom-made fenestrated aortic endografts allow exclusion of pararenal
      aortic aneurysms while maintaining blood flow to aortic branches. Meticulous
      device planning and precise deployment of the main body are essential to allow
      successful cannulation of the fenestrations. This study investigates whether a
      learning curve can be observed with more reliable cannulation and connection of
      fenestrations over time at a single department of vascular and endovascular
      surgery with multiple surgeons trained to use the device. Methods A retrospective
      analysis of data from all patients undergoing primary fenestrated endovascular
      aneurysm repair during the study period was performed. Outcome measures included
      case volume and average number of fenestrations over time, average fluoroscopy
      dose area product per calendar year and primary unconnected fenestration and 30
      day mortality rates. Results Between 1 January 2013 and 31 December 2016, 89
      patients with no history of endovascular aneurysm repair underwent fenestrated
      endovascular aneurysm repair at our institution. The number of fenestrations per
      case increased over time, averaging 2.6 in 2013 and 3.3 in 2016. Primary
      unconnected fenestration and 30-day mortality rates were 5.6%. Primary-assisted
      technical success was 93.3%, secondary-assisted technical success was 94.4%.
      Fluoroscopy dose area product declined over the study period. Thirty-day
      mortality and primary unconnected fenestration rates did not significantly change
      over the study period. Conclusion Albeit the reduction in lethal complications
      and primary technical success rates were not statistically significant, a lower
      percentage of unconnected fenestrations and 30-day mortality per calendar year
      were observed over time. At the same time, an increasing complexity of performed
      cases, as reflected by an increasing number of fenestrations per case, was
      observed. Complications associated with this complex endovascular procedure are
      potentially lethal and remain an unfortunate reality and may not be entirely
      dependent on overcoming a learning curve. A higher volume of cases performed over
      the study period and a reduction in fluoroscopy use can be considered a
      representation of the institutional development and learning curve for the
      Anaconda fenestrated endograft at a department with prior complex endovascular
      aortic repair experience, but due to limitations of the current retrospective
      observation, deserve further consideration in future trials, ideally designed in
      a prospective fashion.

PMID- 30205779
TI  - Association between serum uric acid and carotid disease in patients with
      atherosclerotic acute ischemic stroke.
AB  - Aim The role of serum uric acid in ischemic stroke is controversial. On the one
      hand, it has a role as neuroprotectant in acute phase, but on the other hand, it
      may promote atherosclerosis in carotid arteries. Our aim is to investigate the
      association of serum uric acid levels at admission of acute ischemic stroke
      patients with carotid disease. Methods Cross-sectional study of patients admitted
      due to acute ischemic stroke. Clinical and laboratory variables were recorded.
      The carotid disease was defined based on the findings of carotid echography
      intima to media thickness and stenosis. Patients were grouped according to these
      findings. Robust statistical methods were applied into analysis. Results A total
      of 245 patients were recruited through a stroke registry. Their values of serum
      uric acid were related to both carotid intima to media thickness and stenosis
      showing a positive relationship between serum uric acid levels and intima to
      media thickness by Pearson correlation ( p < 0.05). Similarly, after adjusting
      for all potential confounders, eGFR, glucose, age and serum uric acid levels, (OR
      1.26 (95% CI 1.04 -1.52, p1/40.01), were identified as independent predictors for
      having a intima to media thickness >=1 mm. Similarly, by grouping patients in
      tertiles of the serum uric acid distribution, we found a predominantly greater
      carotid disease in the tertile with the highest levels of serum uric acid ( p <
      0.005). Conclusion Our study supports the hypotheses that serum uric acid levels
      have different roles in the case of ischemic stroke. Its effects on the vascular
      wall contribute to the development of atherosclerosis and carotid disease.

PMID- 30205780
TI  - Transradial interventions in contemporary vascular surgery practice.
AB  - Objectives Upper extremity arterial access is often required for endovascular
      procedures, especially for antegrade access to the visceral aortic branches.
      Radial arterial access has been shown previously to have low complication rates,
      and patients tolerate the procedure well and are able to recover quickly.
      However, transradial access remains relatively uncommon amongst vascular
      surgeons. Methods The radial artery was evaluated by ultrasound to evaluate for
      adequate caliber, and to identify any aberrant anatomy or arterial loops. A
      modified Barbeau test was performed to ensure sufficient collateral circulation.
      A cocktail of nitroglycerin, verapamil and heparin was administered intra
      arterially to combat vasospasm. Sheaths up to 6 French were utilized for
      interventions. On completion of the procedure, a compression band was used for
      hemostasis in all cases. Results Twenty-five interventions were performed in 24
      patients. The left radial artery was used in 23/25 cases (92.0%). Procedures
      included visceral and renal artery interventions; stent graft repair of a renal
      artery aneurysm; embolization of splenic, pancreaticoduodenal and internal
      mammary aneurysms; embolization of bilateral hypogastric arteries following blunt
      pelvic trauma; interventions for peripheral arterial disease; delivery of a renal
      snorkel graft during endovascular aortic aneurysm repair, and access for
      diagnostic catheters during thoracic endovascular aortic aneurysm repair.
      Technical success was 92.0%. There was one post-operative radial artery occlusion
      (4.3%) which led to paresthesias but resolved with anticoagulation. There were no
      instances of arterial rupture, hematoma, or hand ischemia requiring intervention.
      Conclusions Using the transradial approach, we have demonstrated a high technical
      success rate over a range of clinical contexts with minimal morbidity and no
      significant complications such as bleeding or hand ischemia. The safety profile
      compares favorably to historical complication rates from brachial access. Radial
      access is a safe and useful skill for vascular surgeons to master.

PMID- 30205782
TI  - No-brainers in medicine.

PMID- 30205781
TI  - Gender-related outcomes of chimney EVAR within the PERICLES registry.
AB  - OBJECTIVE: Gender-related differences in outcomes in complex endovascular aortic
      repair have not been profoundly investigated. Use of low profile abdominal
      devices as in chimney endovascular repair may be beneficial for female patients
      with pararenal pathologies. With the chimney technique, there is no need for
      large introduction sheaths. This could be an advantage in case of smaller in
      diameter iliac access especially in combination with stenosis or elongation. Aim
      of the present study was to compare the perioperative and mid-term outcomes
      between males and females patients treated with the chimney/snorkel technique for
      pararenal aortic pathologies. METHODS: The PERICLES registry collected the world
      wide experience with the chimney technique. According to the gender, patients
      were classified in two cohorts. Primary endpoints were freedom from occlusion of
      the chimney grafts and reintervention. Secondary endpoints included access site
      complications and need for surgical or interventional revision, Endoleak Type I
      rate, 30-day overall complications and mortality. Univariate comparison P-values
      were generated using either the likelihood ratio chi2 test, the Fisher exact
      test, the Wilcoxon rank sum test, or the log rank test. Kaplan-Meier curves
      estimated the outcomes in the long run. RESULTS: A total of 412 patients
      underwent Ch-EVAR, 71 (17%) females and 341 (83%) males with a mean age for both
      groups being 74 years were included in the present study. After 36 months of mean
      follow-up, no statistically significant difference was observed between the two
      cohorts regarding re-interventions ( P= .44). Freedom from occlusion rates at 36
      months did not differed between the two groups (females 84% vs. 80% for males (
      P= .033). For patients receiving more than one chimney stent, the odds of having
      a complication did not differ between males and females (M:F OR = 2.0, 95% CI:
      0.6-6.4, P = 0.228); 30-day mortality was 0% in the female group, instead five
      male patients died within one month. ( P = 0.59). The incidence of acute renal
      failure was low in both groups without statistical difference: 2 (3.1%) vs. 13
      (4.6%) 58 ( P = 1.00). Neither patient received an endoconduit to insert the
      abdominal device. CONCLUSIONS: No statistically significant difference regarding
      the freedom from reintervention and chimney graft patency was observed between
      the two genders. The results highlight the beneficial use of the chimney
      technique in female patients who can have potentially higher risk of access
      complications.

PMID- 30205783
TI  - Physical Activity and Sedentary Behaviors of Children in Family Child Care Homes:
      Are There Opportunities for Improvement?
AB  - PURPOSE: Many children attend family child care homes (FCCHs), an important
      setting to influence children's physical activity (PA) and sedentary behavior
      (SB). This study assessed children's PA and SB while in FCCHs, characteristics of
      the FCCH PA environment, and relationships between the environment and child PA
      and SB. METHOD: Children ages 1.5-4.0 years (n = 495) were recruited from 165
      FCCHs in North Carolina. Children's moderate to vigorous PA and SB were measured
      via accelerometry for 3 days. FCCH PA environments were assessed over 2 days
      using the Environment and Policy Assessment and Observation for FCCHs. Ten
      subscores and an overall PA environment score (possible range: 0-30) were
      calculated; higher scores indicate better quality. RESULTS: Children accumulated
      30 (13) minutes of moderate to vigorous PA and 143 (42) minutes of SB in FCCHs
      daily. FCCHs scored low on the Environment and Policy Assessment and Observation
      for FCCHs, with an average overall score of 13 (2). FCCHs scored highest on
      screen time and screen time practices subscores, and lowest on PA
      education/professional development and PA policy subscores. Although no
      statistically significant associations were observed, some large Cohen d effect
      sizes were noted (eg, outdoor playtime subscore and moderate to vigorous PA).
      CONCLUSIONS: This study highlights opportunities to improve FCCHs and increase
      children's behaviors (eg, providing adequate time and outdoor play spaces).

PMID- 30205784
TI  - Integrative CNS Plasticity With Exercise in MS: The PRIMERS (PRocessing,
      Integration of Multisensory Exercise-Related Stimuli) Conceptual Framework.
AB  - There is a proliferation of research examining the effects of exercise on
      mobility and cognition in the general population and those with neurological
      disorders as well as focal research examining possible neural mechanisms of such
      effects. However, there is seemingly a lack of focus on what it is about
      exercise, in particular, that drives adaptive central nervous system
      neuroplasticity. We propose a novel conceptual framework (ie, PRIMERS) that
      describes such adaptations as occurring via activity-dependent neuroplasticity
      based on the integrative processing of multisensory input and associated complex
      motor output that is required for the regulation of physiological systems during
      exercise behavior. This conceptual framework sets the stage for the systematic
      examination of the effects of exercise on brain connectivity, brain structure,
      and molecular/cellular mechanisms that explain improvements in mobility and
      cognition in the general population and persons with multiple sclerosis (MS). We
      argue that exercise can be viewed as an integrative, systems-wide stimulus for
      neurorehabilitation because impaired mobility and cognition are common and co
      occurring in MS.

PMID- 30205785
TI  - Impact of Toupet Versus Nissen Fundoplication on Dysphagia in Patients With
      Gastroesophageal Reflux Disease and Associated Preoperative Esophageal
      Dysmotility: A Systematic Review and Meta-Analysis.
AB  - BACKGROUND: Controversy exists regarding the best surgical approach for the
      management of gastroesophageal reflux disease (GORD) and associated preoperative
      esophageal dysmotility. Our aim was to conduct a systematic review and meta
      analysis to compare the outcomes of Toupet fundoplication (TF) and Nissen
      fundoplication (NF) in patients with GORD and coexistent preoperative esophageal
      dysmotility. METHODS: We conducted a systematic search of electronic information
      sources, including MEDLINE, EMBASE, CINAHL, CENTRAL, ClinicalTrials.gov , and
      bibliographic reference lists. We applied a combination of free text search and
      controlled vocabulary search adapted to thesaurus headings, search operators, and
      limits in each of the above-mentioned databases. Postoperative dysphagia and
      improvement in dysphagia were primary outcome parameters. RESULTS: We identified
      3 randomized controlled trials and 1 observational study reporting a total of 220
      patients, of whom 126 underwent TF and the remaining 94 patients had NF. Despite
      the existence of significantly higher preoperative dysphagia in the TF group
      (29.3% vs 4.2%, P = .05), TF was associated with significantly lower
      postoperative dysphagia (odds ratio [OR] = 0.31, P = .002) with low between-study
      heterogeneity ( I2 = 11%, P = .34), and significantly higher improved dysphagia
      (OR = 10.32, P < .0001) with moderate between-study heterogeneity ( I2 = 31%, P =
      .23) compared with NF. CONCLUSION: TF may be associated with significantly lower
      postoperative dysphagia than NF in patients with GORD and associated preoperative
      esophageal dysmotility. However, no definite conclusions can be drawn as the best
      available evidence comes mainly from a limited number of heterogeneous randomized
      controlled trials. Future studies are encouraged to include patients with similar
      preoperative dysphagia status and report the outcomes with respect to recurrence
      of acid reflux symptoms.

PMID- 30205786
TI  - Memory modulation: An introduction to the special issue.
AB  - This Special Issue of Cognitive Neuroscience highlights recent research on the
      cognitive neuroscience of episodic memory, with an emphasis on interventions
      designed to modulate memory processes. Collectively, the nine included papers
      provide a timely overview of the state of memory modulation, including work on
      pharmacological manipulations, motivational states, and targeted brain
      stimulation.

PMID- 30205787
TI  - Morbillivirus-associated lipid pneumonia in Arctic foxes.
AB  - We describe lipid pneumonia in 5 of 24 Arctic foxes ( Vulpes lagopus) in
      association with morbillivirus infection, and lymphoid depletion in 3 of these 5
      foxes. Canine distemper virus (CDV) immunohistochemistry yielded positive
      staining in lung, lymph nodes, spleen, adipose tissue, and renal pelvic
      urothelial cells in 5 cases. Liver and bone marrow samples collected from these
      cases tested positive for morbillivirus by reverse-transcription PCR assay.
      Strains belonged to the CDV Arctic lineage based on sequencing of the
      hemagglutinin gene followed by phylogenetic analysis. Phylogenetic analysis of
      the phosphoprotein gene showed that the identified CDV strains were not closely
      related to any previously documented strains responsible for outbreaks in
      different animals in other parts of the world.

PMID- 30205788
TI  - Effect of Parental Negligence on Mobile Phone Dependency Among Vulnerable Social
      Groups: Mediating Effect of Peer Attachment.
AB  - The purpose of this study was to investigate the association between perceived
      parental negligence and reliance on mobile phone usage among youth in vulnerable
      social groups, and whether peer attachment mediates this association.
      Specifically, we aimed to provide in-depth information on the relationship
      between perceived parental negligence and mobile phone dependency by examining
      the mediating effects of three subfactors of peer attachment: communication,
      trust, and isolation. For this purpose, we analyzed the longitudinal data of 485
      elementary school students in grades 4 to 6 who were attending a community
      children's center. The results were as follows: (1) parental negligence had a
      statistically significant positive effect on all subfactors of peer attachment;
      (2) while communication and trust were not significantly related to mobile phone
      dependency, isolation was related to mobile phone dependency; and (3) while
      perceived parental negligence did not have a direct effect on mobile phone
      dependency, it did have an indirect effect via isolation (a dimension of peer
      attachment).

PMID- 30205789
TI  - The Effectiveness of Group Hope Therapy in Labor Pain and Mental Health of
      Pregnant Women.
AB  - In the present study, the effect of group hope therapy on labor pain and mental
      health of pregnant women was investigated, in consideration of the Iranian health
      policy's emphasis on encouraging women to have a healthy delivery. The research
      plan was a semiexperimental pretest-posttest design with a control group. A total
      of 36 pregnant women were assigned to the treatment and control group using a
      random procedure. General Health Questionnaire and a Visual Analog Scale were
      used to collect data about dependent variables. For the analysis of hypotheses,
      independent samples t test and covariance analysis were used. The findings showed
      that hope therapy had a significant effect on labor pain (t = 5.17; P < 0.001)
      and mental health (F = 28.21; P < 0.001). In general, the findings of the present
      study confirm the application of group hope therapy in relieving labor pain and
      increasing the mental health of pregnant women. This therapeutic approach can
      simultaneously reduce the labor pain, generate positive emotions in women, and
      turn the experience of delivery into a pleasant one.

PMID- 30205790
TI  - Medicinal plants and atherosclerosis: A review on molecular aspects.
AB  - Atherosclerosis is an inflammatory vascular disease that is characterized by
      progressive accumulation of cholesterol in the arterial walls and it is a major
      cause of cardiovascular disease. Issues related to the side effects of synthetic
      drugs have in recent times, led to the misuse of drugs, a lack of patient
      consultations, and consequently, a disruption in meticulous disease control.
      Therefore, a new insight into medicinal plants has recently emerged and much
      research has been conducted on these herbs in an attempt to prepare novel
      naturally based drugs. The aim of this review article was to scrutinize the
      molecular mechanisms of medicinal plants possessing effectiveness against
      atherosclerosis. To conduct the review, electronic searches were performed to
      retrieve potentially relevant publications, indexed within internet databases and
      reference textbooks concerning the effects and underlying molecular mechanisms of
      plants or their constituents used to treat atherosclerosis. Overall, medicinal
      plants facilitate atherosclerosis treatment through a variety of mechanisms which
      include the regulation of expression of inflammatory factors, stimulation of
      peroxisome proliferator-activated receptors (PPARs), inhibition of 3-hydroxy-3
      methyl-glutaryl-coenzyme A reductase (HMG-CoA reductase), promotion of ATP
      binding cassette transporter A1 (ABCA1) as well as ATP-binding cassette
      transporter G (ABCG), facilitation of adiponectin activity, reduction of sterol
      regulatory element-binding proteins (SREBPs) and antioxidant activity. An
      increased perception of these herbal mechanistic links is an important prelude to
      the design of novel plant based drugs.

PMID- 30205791
TI  - Tumor Necrosis Factor-alpha and C-C Motif Chemokine Ligand 18 Associate with
      Atherosclerotic Lipid Accumulation In situ and In vitro.
AB  - Atherosclerosis is regarded as a chronic inflammatory disease associated with
      changes in the innate immune system functioning and cytokine disturbances. Local
      inflammation in the arterial wall is an important component in the development
      and growth of atherosclerotic plaques. Inside the lesions, both pro- and
      antiinflammatory cytokines were detected, highlighting the complexity of the
      atherosclerotic process. However, little is known about the expression of these
      signaling molecules in early human atherosclerotic lesions. In this study, we
      explored localization of a pro-inflammatory cytokine, tumor necrosis factor-alpha
      (TNFalpha), and anti-inflammatory chemokine, C-C motif chemokine ligand 18
      (CCL18), in the arterial wall of human aorta. We noticed differences in the
      intensity of staining for TNFalpha and CCL18 in atherosclerotic lesions and
      grossly normal areas, as well as differences in their localization. While CCL18
      prevailed in the areas close to the aortic lumen, TNFalpha was localized in
      deeper layers of the intima. We next studied the expression of TNFalpha and CCL18
      mRNA in lesions corresponding to different stages of atherosclerosis progression
      and found that it was maximal in lipofibrous plaques that are most enriched in
      lipids. To test the hypothesis that cytokine expression can be associated with
      lipid accumulation, we studied the TNFalpha and CCL18 expression profiles in
      primary human monocyte-derived macrophages after inducing lipid accumulation by
      incubating cultured cells with atherogenic LDL. We found that intracellular
      cholesterol accumulation was associated with upregulation of both TNFalpha and
      CCL18, confirming our hypothesis. These results encourage further investigation
      of cytokine expression in human atherosclerotic lesions and its role in the
      atherosclerosis progression.

PMID- 30205793
TI  - Coronary Microcirculation and the No-reflow Phenomenon.
AB  - The no-reflow phenomenon refers to the post-percutaneous coronary intervention
      condition in which, despite re-establishing epicardial coronary vessel patency,
      the flow to the previously ischemic myocardium is markedly reduced. When it does
      occur, it attenuates the beneficial effect of reperfusion therapy and substantial
      regions of the myocardium fail to receive adequate perfusion. The pathophysiology
      of this phenomenon is not completely understood. The possible mechanisms could be
      related to alterations in the microvascular circulation. Various mechanisms such
      as activation of inflammatory pathways, vascular damage and hemorrhage, leukocyte
      infiltration, and cellular edema may be responsible. As the no-reflow phenomenon
      is associated with adverse clinical consequences, it is of great importance to
      identify exact responsible mechanisms and apply effective preventive and
      therapeutic strategies. In this review, we describe an updated overview of the
      pathophysiological mechanisms and the current preventive tools for no-reflow as
      well as therapeutic interventions in order to improve coronary blood flow and
      consequently the prognosis for these patients.

PMID- 30205792
TI  - Modified Ldl Particles Activate Inflammatory Pathways In Monocyte-Derived
      Macrophages: Transcriptome Analysis.
AB  - A hallmark of atherosclerosis is its complex pathogenesis, which is dependent on
      altered cholesterol metabolism and inflammation. Both arms of pathogenesis
      involve myeloid cells. Monocytes migrating into the arterial walls interact with
      modified low-density lipoprotein (LDL) particles, accumulate cholesterol and
      convert into foam cells, which promote plaque formation and also contribute to
      inflammation by producing pro-inflammatory cytokines. A number of studies
      characterized transcriptomics of macrophages following interaction with modified
      LDL, and revealed alteration of the expression of genes responsible for
      inflammatory response and cholesterol metabolism. However, it is still unclear
      how these two processes are related to each other to contribute to
      atherosclerotic lesion formation. We attempted to identify the main mater
      regulator genes in macrophages treated with atherogenic modified LDL using a
      bioinformatics approach. We found that most of the identified genes were involved
      in inflammation, and none of them was implicated in cholesterol metabolism. Among
      the key identified genes were interleukin (IL)-7, IL-7 receptor, IL-15 and CXCL8.
      Our results indicate that activation of the inflammatory pathway is the primary
      response of the immune cells to modified LDL, while the lipid metabolism genes
      may be a secondary response triggered by inflammatory signalling.

PMID- 30205794
TI  - The Dual Specificity Role of Transcription Factor FOXO in Type 2-diabetes and
      Cancer.
AB  - The FOXO (Forkhead box O) transcription factors are implicated in several
      signaling pathways and play a vital role in various cellular and physiological
      processes include for instance, ROS (reactive oxygen species) response, cell
      proliferation, regulation of programmed cell death, longevity, metabolism and
      cancer and regulation of cell cycle. In humans, the four FOXO family members are
      responsible for resemblance in their structure, regulation and functions. FOXO1
      gene is highly expressed in adipose tissues and it affects the regulation of
      glycogenolysis and gluconeogenesis through insulin signaling. The gene of FOXO3
      is highly expressed in the kidney, heart, spleen and brain and is characterized
      as diverse forkhead DNA-binding domain of transcription factors. The FOXO3 is a
      tumor suppressor gene and found to interact with p53, the trigger for apoptosis
      through BCl2 family genes and a regulator of Notch signaling pathway for the self
      renewal of stem cells. Therefore, FOXOs remains to be a fascinating and potential
      target to acquire novel therapeutic approaches to cure cancer. This review will
      provide a comprehensive overview about the biology of FOXO proteins, which can be
      utilized for developing current therapeutic approaches to treat cancer.

PMID- 30205795
TI  - Translation of Basic Research into Clinics: Killer Immunoglobulin-like Receptors
      Genes in Autoimmune and Infectious Diseases.
AB  - Killer immunoglobulin-like receptors regulate the activation of natural killer
      cells through their interaction with human leucocyte antigens. Killer
      immunoglobulin-like receptors and human leucocyte antigens loci are highly
      polymorphic, and some their combinations have been found to protect against viral
      infections or to predispose to autoimmune disorders. In particular, some
      activating killer immunoglobulin-like receptors profiles may be detrimental in
      autoimmune pathogenesis, and specific killer immunoglobulin-like receptors genes
      may be particularly aggressive in the clearance of different microorganisms,
      protecting individuals in the control of a given pathogen. So, considering the
      role of the innate immunity in the pathogenesis of many autoimmune and infection
      diseases, the recent development for killer immunoglobulin-like receptors
      characterization, diseases monitoring, and treatment becomes obvious. Here we
      reviewed a growing body of evidence supporting the influence of killer
      immunoglobulin-like receptor variants and their interaction with the ligand in
      the development of the main human autoimmune and viral diseases, highlighting the
      main applications in clinical practises.

PMID- 30205796
TI  - Medicinal plants for the treatment of hair loss and the suggested mechanisms.
AB  - Hair loss may not be recognized as a life-threatening disorder. However, it has a
      great harm on a person's self-respect, mental health, and entirety quality of
      life. Androgenic alopecia (AGA) is the most common type of hair loss, which
      affects a great number of both men and women. Alopecia can be treated with
      various hair loss strategies, including hair transplant, cosmetics and
      medication. Medical treatment shows the outstanding ability in improving hair
      growth. Plenty of drugs prevent alopecia by inhibiting the secretion of male
      hormone. But these medicines exhibit some undesirable side effects. Since hair
      loss requires a long-term treatment, and minimizing adverse side effects is
      extremely urgent in drug development. Accordingly, new agents are obtained from
      natural products with less adverse effects. Traditional Chinese medicines exhibit
      unique advantages in hair loss treatment. This review generalizes and analyzes
      the recent progress of medicinal plants for the treatment of hair loss, suggested
      mechanisms and outlines a number of trials taken or underway to optimize the
      treatment.

PMID- 30205797
TI  - In Vitro and In Vivo Antimetastatic Effects of ZSTK474 on Prostate Cancer DU145
      Cells.
AB  - BACKGROUND: Metastasis is the main cause of lethality of prostate cancer.
      Inhibition of metastasis is expected to be a promising approach for prostate
      cancer therapy. Phosphatidylinositol 3-kinase (PI3K)/Akt pathway is known to play
      key roles in cell growth, migration, etc. Objective: Investigate the
      antimetastatic activities of pan-PI3K inhibitor ZSTK474 on prostate cancer DU145
      cells. METHODS: 1. In vitro effect of ZSTK474 on the migration, invasion and
      adhesion of DU145 cells was determined with Transwell migration assay and wound
      healing assay, Tranwell invasion assay, and adhesion assay, respectively. 2. In
      vitro effect of ZSTK474 on the signal proteins in DU145 cells was determined with
      Western blot analysis and ELISA. 3. In vivo antimetastatic effect of ZSTK474 was
      evaluated with MicroCT and histology analysis. RESULTS: ZSTK474 potently
      inhibited migration, invasion and adhesion of DU145 cells, negatively regulated
      Girdin, Integrin?1 and matrix metalloproteinases (MMPs). In addition, the
      expression of hypoxia inducible factor-1alpha (HIF-1alpha) and vascular
      endothelial growth factor (VEGF), which are known to be related to angiogenesis
      and metastasis, was also inhibited. Oral administration of ZSTK474 (200 mg/kg)
      ameliorated in vivo bone metastasis of DU145 cells, with improved bone structure
      and bone mineral density (BMD). Tissue staining indicated reduction of metastatic
      DU145 cells and osteoclasts in the bones of ZSTK474-treated mice, compared with
      the non-treated group. CONCLUSION: Our result demonstrated the in vitro and in
      vivo antimetastatic effect of pan-PI3K inhibitor ZSTK474 on prostate cancer DU145
      cells, suggesting the potential application in prostate cancer patients.

PMID- 30205798
TI  - Non-hormonal replacement therapy regimens: do they have an effect on
      cardiovascular risk?
AB  - INTRODUCTION: Menopause is associated with adverse effects on quality of life of
      peri-menopausal and post-menopausal women. It also has an impact on the
      development of cardiovascular disease (CVD). Hormonal treatments are the most
      effective medications for menopausal symptoms relief. Given the fact that
      hormonal treatments are contraindicated for many women, non-hormonal treatment,
      such as Selective Serotonin Reuptake Inhibitors (SSRIs), Serotonin and
      Norepinephrine Reuptake Inhibitors (SNRIs), gabapentin, pregabalin, clonidine and
      phytoestrogens, constitute alternative treatments. Nevertheless, little is known
      about their effects on CVD risk. METHODS: PubMed, EMBASE and Cochrane Library
      were searched for the effects of non-hormonal treatment on CVD risk, blood
      pressure, heart rate, lipids and glucose concentrations, weight gain,
      cardiovascular events, stroke, mortality and morbidity. RESULTS: Phytoestrogens,
      pregabalin and gabapentin seem to have no adverse effects on the cardiovascular
      system. Phytoestrogens, in particular, seem to reduce CVD risk through many
      pathways. On the other hand, SSRIs and SNRIs, although effective in reducing
      menopausal vasomotor symptoms, should be cautiously administered to women with
      known CVD (e.g. with cardiac arrhythmias, atherosclerotic disease or stroke). As
      clonidine has been associated with cardiovascular adverse effects, it should be
      administered only in cases where blood pressure regulation is mandatory.
      CONCLUSION: Further research is needed to produce definite conclusions regarding
      the cardiovascular safety of non-hormonal medications for menopausal symptoms
      relief.

PMID- 30205799
TI  - Involvement of intracellular pH in vascular insulin resistance.
AB  - The maintenance of the pH homeostasis is maintained by several mechanisms
      including the efflux of protons (H+) via membrane transporters expressed in
      almost all mammalian cells. Along these membrane transporters the sodium/H+
      exchangers (NHEs), mainly NHE isoform 1 (NHE1), plays a key role in this
      phenomenon. NHE1 is under modulation by several environmental conditions (v.g.,
      hyperglycaemia, protein kinase C activity) as well as hormones, including
      insulin. NHE1 activation causes intracellular alkalization in human endothelial
      cells leading to activation of the endothelial nitric oxide synthase (eNOS) to
      generate NO. Intracellular alkalization is a phenomenon that also results in
      upregulation of the glucose transporter GLUT4 in cells that are responsive to
      insulin. A reduction in the removal of the extracellular D-glucose is seen in
      states of insulin resistance, such as in diabetes mellitus and obesity. Since
      insulin is a potent activator of eNOS in human endothelium, therefore causing
      vasodilation, and its vascular effect is reduced in insulin resistance it is
      likely that a defective signal to activate NHE1 in insulin target cells is
      expected. This phenomenon results in lower redistribution and activation of GLUT4
      leading to reduced uptake of D-glucose and hyperglycaemia. The general concept of
      a role for NHE1, and perhaps other NHEs isoforms, in insulin resistance in the
      human vasculature is proposed.

PMID- 30205800
TI  - Therapeutic Potential of Stem Cells for Bronchopulmonary Dysplasia: "It's about
      time" or "Not so fast" ?
AB  - While the survival of extremely premature infants improved over the past decades,
      the rate of complications - especially for bronchopulmonary dysplasia (BPD) -
      remains unacceptably high. Over the past 50 years, no safe therapy has had a
      substantial impact on the incidence and severity of BPD. This may stem from the
      multifactorial disease pathogenesis and the increasing lung immaturity.
      Mesenchymal stromal cells (MSCs) display pleiotropic effects and showed promising
      results in neonatal rodents in preventing or rescuing lung injury without adverse
      effects. Early phase clinical trials are now underway to determine the safety and
      efficacy of this therapy in the extremely premature infants. This review
      summarizes our current knowledge about MSCs, their mechanism of action and the
      results of preclinical studies that provided the rationale for early phase
      clinical trials and discuss our remaining gaps in knowledge.

PMID- 30205801
TI  - Nano-based therapy for treatment of skin cancer.
AB  - BACKGROUND: According to the World Health Organization, skin cancer is the most
      common malignancy for the population. Conventional skin cancer treatment includes
      surgery and chemotherapy, but many of the chemotherapeutic agents used present
      undesirable properties. There are number of patents on topical nano formulation
      like nanoparticle (US9757453; US9457041), liposomes (US2018177726 (A1), has been
      covered in this review in the treatment of skin cancer. METHODS: Encapsulated
      drugs are advantageous due to such properties as high stability, better
      bioavailability, controlled drug release, a long blood circulation time,
      selective organ or tissue distribution, a lower total required dose, and minimal
      toxic side effects. Today, researchers are constantly developing new formulations
      to meet unmet needs in the delivery of therapeutic agents for cancer therapy and
      diagnosis, respectively. RESULTS: Of particular interest here are lipid-based
      nano formulations that are formulated from varieties of lipid and other chemical
      components that act collectively to overcome biological barriers, in order to
      preferentially accumulate in or around disease-target cells for the functional
      delivery of therapeutic agents. The article deals with recent development of nano
      sized topical lipid formulation approaches to treat skin cancer. CONCLUSION: We
      focus especially on the topical lipid formulation approaches combined with
      chemotherapy, a field which specialises in target specificity, drug release
      control, and real time monitoring with the goal being to diminish unwanted side
      effects and their severity, achieving a cheaper treatment and a generally more
      efficient chemotherapy.

PMID- 30205802
TI  - Celastrus Orbiculatus Extract Potentiates The Sensitivity Of Cisplatin Via
      Caspase-Depenent Apoptosis In Gastric Cancer.
AB  - BACKGROUND: Cisplatin-based treatment often leads to therapeutic failure because
      the acquisition of cisplatin resistance. The combination of cisplatin with other
      agents has been recognized as a promising strategy to overcome cisplatin
      resistance. OBJECTIVE: Celastrus orbiculatus is a traditional Chinese medicine
      from Celastraceae family with multiple pharmacological activities. We previously
      found the the ethyl acetate extract of Celastrus orbiculatus (COE) exhibited
      significant antitumor activity in gastric cancer. Here, we asked whether COE
      could increase the sensitivity of cisplatin. METHODS: We use CCK8 assay to show
      synergistic cytotoxicity of COE and cisplatin. Then, PI single staining and FITC
      Annexin V/PI double staining were used to observe apoptotic cells through flow
      cytometry. The proteins of caspase signaling pathway were examined by Western
      blotting Results: COE and cisplatin showed synergistic cytotoxicity in a dose
      dependent manner in BGC 823 and SGC 7901 gastric cancer cells, and COE could
      increase the number of apoptotic cells upon cisplatin treatment in vitro.
      Moreover, our results indicated that COE could enhance cisplatin-induced
      activation of caspase-8 or caspase-9/caspase-3/PARP1 signaling pathways. The
      xenograft study further confirmed that COE increased the sensitivity of cisplatin
      in vivo Conclusion: Our findings provided new evidence that COE could increase
      the sensitivity of cisplatin on the antitumor effect.

PMID- 30205803
TI  - Synthesis And In Vitro/In Vivo Characterization Of Raloxifene Grafted
      Poly(Styrene Maleic Acid)-Poly (Amide-Ether-Ester-Imide!!) Micelles For Targeted
      Delivery Of Docetaxel In G Protein-Coupled Estrogen Receptor Breast Cancer.
AB  - BACKGROUND: To reduce the nonspecifically distribution of chemotherapeutic agents
      throughout the whole body, which causes severe toxicity in normal tissues,
      targeting them towards a receptor overexpressed on tumor tissue, is a promising
      method for cancer therapy. OBJECTIVE: The aim of the present study was
      development of novel copolymeric micelles of raloxifene targeted styrene maleic
      acid-poly amide ether ester imide-poly ethylene glycol (SMA-PAEEI-PEG-RA) and
      loading them with docetaxel (DTX). METHODS: Successful synthesis of the targeted
      copolymer was confirmed by FTIR and C-NMR spectroscopy. The micelles
      physicochemical properties like morphology, particle size, poly dispersity index,
      zeta potential, drug loading, release, stability, in vitro cytotoxicity and
      cellular uptake were analyzed. The in vivo antitumor activity of DTX-loaded
      micelles were assessed and compared with free DTX and non-targeted micelles in
      breast cancer bearing Balb-c mice. RESULTS: Particle sizes, zeta potentials and
      the encapsulation efficiency of the drug in targeted micelles were 115.9-142.8
      nm, -4.9 to -12.9 mV, and 54.1-67.8%, respectively. Cell toxicity tests showed
      that IC50 of DTX-loaded SMA-PAEEI-PEG-RA micelles increased five-fold as compared
      with free DTX. Survival rate of the mice improved more effectively than free DTX
      so that, the percentage of increase in lifespan (ILS%) and the tumor inhibition
      ratio (TIR) changed from 41.66% and 51.19% in free drug to 83.33% and 78.57% in
      the targeted micelles, respectively. CONCLUSION: Therefore, the raloxifene
      conjugated PEG-derived micelles may provide a novel and effective delivery system
      for DTX in breast cancer.

PMID- 30205804
TI  - Aberrant Sialylation in Cancer Pathology and Metastasis, a Putative Drug Target
      Candidate.
AB  - BACKGROUNDS: Neoplasm metastasis is a multi-step and multi-level pathological
      feature causing 90% of cancer mortality due to a shortage of effective drugs and
      clinical therapeutics. To change this scenario, new drug targets and developments
      are required. METHOD: Aberrant tumor sialylation as a putative drug target
      candidate has been evolving over the past half century. Some specific agents and
      clinical events suggested some promising therapeutic potentiality and benefits
      against neoplasm metastasis in a number of cellular and animal tumor models.
      RESULTS: Since neoplasm tissues often contain higher levels and diverse sialic
      acids (sia) analogues and antigens, sia-related tumor biology/pathology are
      emerging as cancer diagnostic categories and a series of useful agents until now.
      Previously some compounds enabling to inhibit sia-related pathologic pathways
      were reported to exhibit therapeutic activity in cellular or animal tumor models.
      These types of cancer treatment agents can provide excellent therapeutic outcomes
      by glycome/metabolomics diagnostics first. CONCLUSION: Taking together of these
      experimental/clinical discoveries, the "central dogma" of glycobiology might be
      found out via all these principle discoveries. In addition, mathematic- or
      physics-majored talents might render new therapeutic discoveries by computational
      analysis of experimental and clinical data. Overall, therapeutic targets/benefits
      in the clinic should be pursuit with earnest attitude.

PMID- 30205805
TI  - Pinocembrin-Enriched Fractions of Elytranthe parasitica (L.) Danser Modulates
      Apoptotic and MAPK Cellular Signaling in HepG2 cells Pinocembrin-Enriched
      Fractions of Elytranthe parasitica (L.) Danser Modulates Apoptotic and MAPK
      Cellular Signaling in HepG2 cells.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is the fifth leading cause of cancer
      mortality. Elytranthe parasitica (L.) Danser (EP), a hemiparasitic plant
      (Loranthaceae) has potent anti-cancer properties. OBJECTIVE: In the study, we
      investigated the effect of EP fractions on expression of apoptosis and mitogen
      activated protein kinase (MAPK) markers deregulated in HCC. Bioactivity
      fractionation was performed to isolate the phytochemical(s) exerting anti-tumor
      activity in HepG2 cells. METHOD: Anti-proliferative, clonogenic and anti
      metastatic effects of EP fractions was examined in hepatocellular carcinoma cell
      line, HepG2 by Sulphorhodamine B, colony formation and scratch wound assays
      respectively in hepatocellular cell line, HepG2. The effects of EP fractions on
      key markers of apoptosis and MAPK signaling pathways were explored. KEY FINDINGS:
      EP bioactive fractions showed significant anti-tumor potential, reduced
      clonogenicity and considerably inhibited cell migration in HepG2 cells in vitro.
      The fractions augmented annexin V binding and induced apoptosis by causing cell
      cycle arrest at G2/M and S phase checkpoints. The fractions increased expression
      levels of p53, bad, cleaved PARP (Poly ADP ribose polymerase) and cleaved Caspase
      3. Expression levels of phosphorylated ERK1/2 (Extracellular signal-regulated
      kinase) was downregulated. Pinocembrin-7-O-beta-D-glucoside and chrysin were
      isolated and characterized for the first time from Elytranthe parasitica (L.)
      Danser. CONCLUSION: Our findings reveal that EP fractions induced cell cycle
      arrest and triggered apoptosis in HepG2 cells by upregulating apoptosis and
      deactivating MAPK pathway. It signifies that pinocembrin glycoside and chrysin
      are bioactive phytochemicals contributing to the potent anti-hepatocarcinoma
      effects on HepG2 cells. Hence, bioactive EP fractions could be used as a
      therapeutic agent for effective HCC therapy.

PMID- 30205806
TI  - Silimarin and Cancer.
AB  - Silimarin is the dry mixture of a whole family of natural substances, extracted
      after the addition of ethanol, methanol, and acetone. Silimarin consists mainly
      of silibin A and silibin B, as well as other less important compounds. Silimarin
      has been demonstrated to "inhibit cell proliferation and to induce apoptosis,
      while also having anti-angiogenic properties." The induction of apoptosis in
      cancer cells has been mediated by the involvement of ER stress. Silibinin has the
      potential to operate as a STAT3-targeted inhibitor as well as an inhibitor of the
      upregulation of the immune checkpoint regulator PD-L1 and also EMT regulators,
      thus being a promising adjuvant in NSCLC. It has also been documented to suppress
      cancer cells be means of down- regulating actin cytoskeleton and PI3K / Akt
      molecular pathways. Several studies have demonstrated that silibinin exerts its
      protective potential partly through interacting with the tumor suppressor gene
      p53. It is noteworthy that research has been carried out on the enhancement of
      silimarin's bioavailability, especially by the preparation of specific
      nanoformulas, and its probable additional use together with the chemotherapeutic
      regimens in the near future.

PMID- 30205807
TI  - Protective effects of curcumin against toxic agents-induced renal failure: a
      review.
AB  - Curcumin, is the major phenolic compound the rhizome of the Curcuma species that
      is used in herbal medicine. Several studies has showed the protective effects of
      curcumin against nephrotoxi agents such as gallic acid, glucose, tartrazine,
      streptozotocin, lead, maleate, malathion, nicotine, cisplatin, gentamicin and
      methotrexate. However, due to the lake of linical trial studies, more
      investigation are needed to determine the efficacy of curcumin as an antidote
      agent. The present study aimed to critically review the recent literature data
      from that regarding the protective effects of curcumin against nephrotoxin
      agents.

PMID- 30205808
TI  - Maximizing Biomass and Lipid Production in Heterotrophic Culture of Chlorella
      vulgaris: Techno-Economic Assessment.
AB  - BACKGROUND: Nowadays, chlorophycean microalgae have attained a broad-spectrum
      attention as potential candidate for biomass and bioenergy production. Despite
      their appreciated benefits, one of major problems is their low biomass and lipid
      productivity. Here we investigated the heterotrophic culture in shake flasks and
      stirred tank bioreactor to improve the lipid and biomass production in a
      naturally isolated strain of Chlorella vulgaris. METHODS: A naturally isolated C.
      vulgaris strain was cultivated in BG-11 medium in shake flask and bioreactor. Its
      biochemical composition and growth kinetic parameters was investigated. RESULTS:
      The biomass productivity was improved (3.68 fold) under heterotrophic culture
      compared to basal autotrophic culture condition in shake flask experiment. The
      total lipid content was increase to 44% of total Dry Cell Weight (DCW) during
      heterotrophic growth after 21 days. Moreover, a great Fatty Acid Methyl Esters
      (FAME) yield was observed under heterotrophic cultivation. Total biomass and
      lipid content of microalgae in bioreactor experiment increased to 4.95 and 2.18 g
      L-1 respectively during 5 days of experiment compared to its basic autotrophic
      culture. CONCLUSION: The techno-economic aspects of exploiting C. vulgaris as a
      biodiesel feedstock was also evaluated. The results imply that heterotrophic
      cultivation could compensate the low biomass productivity in microalgae for green
      energy production. Ever growing rates of established patents on application of
      various genetic and bioengineering-based methods have made it possible to achieve
      higher lipid contents with reduced total costs for microalgal biodiesel
      production as well.

PMID- 30205809
TI  - Serum PCSK9 levels, but not PCSK9 polymorphisms, are associated with CAD risk and
      lipid profiles in southern Chinese Han population.
AB  - BACKGROUND: Genetic and environment factors affect the occurrence and development
      of coronary artery disease (CAD). Proprotein convertase subtilisin/kexin type 9
      (PCSK9), has been investigated extensively in the field of lipid metabolism and
      CAD. We performed this case-control study to investigate the relationship between
      serum PCSK9 levels and PCSK9 polymorphisms and lipid levels and CAD risk in a
      southern Chinese population. METHODS: A hospital-based case-control study with 1,
      096 subjects, including 626 CAD patients and 470 controls, were conducted.
      Genotyping of PCSK9 polymorphisms was performed using polymerase chain reaction
      ligase detection reaction (PCR-LDR) method. RESULTS: The frequencies of the AA,
      AG and GG genotypes of PCSK9 E670G polymorphism were 90.58, 9.27, and 0.16% in
      the CAD patients, compared with 88.72, 10.85 and 0.43% in the controls,
      respectively. No R46L variant was detected in this population. There were no
      significant differences in genotype and allele frequencies of PCSK9E670G
      polymorphism between the CAD group and the controls. Serum lipid levels were not
      significantly different in carriers with the G allele and those with the AA
      genotype. The median (QR) of PCSK9 concentration was 1205.00 ng/l (577.28-1694.13
      ng/l) in cases and 565.87 ng/l (357.17-967.50 ng/l) in controls, respectively.
      Compared with controls, CAD patients had significantly higher PCSK9 levels (z =
      4.559, P < 0.001). After adjusting for age, gender, essential hypertension,
      diabetic mellitus, smoking and lipid profiles, PCSK9 levels remain significantly
      associated with increased CAD susceptibility (OR = 1.002, 95% CI = 1.001-1.002, P
      < 0.001). The correlation analyses showed that serum PCSK9 levels were positively
      associated with triglyceride (TG), Apo B and atherogenic index of plasma (AIP)
      levels in controls. No significant association between the PCSK9 E670G
      polymorphism and serum PCSK9 levels was observed in the CAD group and the
      controls. CONCLUSIONS: The present study shows that serum PCSK9 levels, but not
      PCSK9 polymorphisms, are associated with CAD risk in Southern Chinese Han
      population, and that serum PCSK9 levels are positively associated with AIP.

PMID- 30205810
TI  - The fatty liver index (FLI) and incident hypertension: a longitudinal study among
      Chinese population.
AB  - BACKGROUND: Hypertension and nonalcoholic fatty liver both have been considered
      as the serious public health problems in recent years. However, the longitudinal
      association between hypertension and nonalcoholic fatty liver remains unclear in
      Chinese population. METHODS: This study was aimed to investigate the longitudinal
      association between nonalcoholic fatty liver assessed by fatty liver index and
      the incident hypertension among Chinese population and to evaluate the ability of
      FLI index, through comparing with the predictive value of other indexes. RESULTS:
      Four thousand six hundred eighty-six subjects (3177 males and 1509 females) were
      involved and followed up for 9 years. The subjects were divided into groups
      according to the fatty liver index. Univariate and multivariate Cox regression
      models were used to analyze the risk factors of hypertension. After 9 years of
      follow-up, 2047 subjects developed hypertension. The overall 9-year cumulative
      incidence of HTN was 43.7%, ranging from 36.0% (FLI <  30) to 75.3% (FLI >= 60)
      (P for trend < 0.001). Cox regression analyses indicated that nonalcoholic fatty
      liver assessed by fatty liver index was independently and positively associated
      with the risk of incident hypertension. In receiver operating characteristic
      (ROC) curve analysis, the ROC curve (AUC) of FLI was 0.701 (95% CI 0.686-0.716),
      which was larger than that of its components. CONCLUSION: The nonalcoholic fatty
      liver assessed by FLI independently predicted the incident hypertension among the
      Chinese population.

PMID- 30205811
TI  - An exploratory study examining how nano-liquid chromatography-mass spectrometry
      and phosphoproteomics can differentiate patients with advanced fibrosis and
      higher percentage collagen in non-alcoholic fatty liver disease.
AB  - BACKGROUND: Non-alcoholic steatohepatitis (NASH) is among the leading causes of
      liver disease worldwide. It is increasingly recognized that the phenotype of NASH
      may involve a number of different pathways, of which each could become important
      therapeutic targets. The aim of this study is to use high resolution mass
      spectrometry (MS) and phosphoproteomics techniques to assess the serum proteome
      and hepatic phosphoproteome in subjects with NASH-related fibrosis. METHODS:
      Sixty-seven biopsy-proven NAFLD subjects with frozen sera and liver tissue were
      included. Reverse phase protein microarray was used to quantify the
      phosphorylation of key signaling proteins in liver and nano-liquid chromatography
      (LC)-MS was used to sequence target biomarkers in the serum. An image analysis
      algorithm was used to quantify the percentage of collagen (% collagen) using
      computer-assisted morphometry. Using multiple regression models, serum proteomes
      and phosphorylated hepatic proteins that were independently (p <= 0.05)
      associated with advanced fibrosis (stage >= 2) and higher % collagen were
      assessed. RESULTS: Phosphorylated signaling pathways in the liver revealed that
      apoptosis signal-regulating kinase 1, mitogen-activated protein kinase (ASK1-MAPK
      pathway involving ASK1 S38 (p < 0.02) and p38 MAPK (p = 0.0002)) activated by the
      inflammatory cytokine interleukin (IL-10) (p < 0.001), were independently
      associated with higher % collagen. LC-MS data revealed that serum alpha-2
      macroglobulin (alpha2M) (p = 0.0004) and coagulation factor V (p = 0.0127) were
      independently associated with higher % hepatic collagen. CONCLUSIONS:
      Simultaneous profiling of serum proteome and hepatic phosphoproteome reveals that
      the activation of ASK1 S38, p38 MAPK in the liver, and serum alpha2M and
      coagulation factor V are independently associated with hepatic collagen
      deposition in patients with NASH. These data suggest the role of these pathways
      in the pathogenesis of NASH-related fibrosis as a potential therapeutic target.

PMID- 30205812
TI  - Physical prognostic factors predicting outcome following lumbar discectomy
      surgery: systematic review and narrative synthesis.
AB  - BACKGROUND: Success rates for lumbar discectomy are estimated as 78-95% patients
      at 1-2 years post-surgery, supporting its effectiveness. However, ongoing pain
      and disability is an issue for some patients, and recurrence contributing to
      reoperation is reported. It is important to identify prognostic factors
      predicting outcome to inform decision-making for surgery and rehabilitation
      following surgery. The objective was to determine whether pre-operative physical
      factors are associated with post-operative outcomes in adult patients [>=16 years
      old] undergoing lumbar discectomy or microdiscectomy. METHODS: A systematic
      review was conducted according to a registered protocol [PROSPERO
      CRD42015024168]. Key electronic databases were searched [PubMed, CINAHL, EMBASE,
      MEDLINE, PEDro and ZETOC] using pre-defined terms [e.g. radicular pain] to
      31/3/2017; with additional searching of journals, reference lists and unpublished
      literature. Prospective cohort studies with >=1-year follow-up, evaluating
      candidate physical prognostic factors [e.g. leg pain intensity and straight leg
      raise test], in adult patients undergoing lumbar discectomy/microdiscectomy were
      included. Two reviewers independently searched information sources, evaluated
      studies for inclusion, extracted data, and assessed risk of bias [QUIPS]. GRADE
      determined the overall quality of evidence. RESULTS: 1189 title and abstracts and
      45 full texts were assessed, to include 6 studies; 1 low and 5 high risk of bias.
      Meta-analysis was not possible [risk of bias, clinical heterogeneity]. A
      narrative synthesis was performed. There is low level evidence that higher
      severity of pre-operative leg pain predicts better Core Outcome Measures Index at
      12 months and better post-operative leg pain at 2 and 7 years. There is very low
      level evidence that a lower pre-operative EQ-5D predicts better EQ-5D at 2 years.
      Low level evidence supports duration of leg pain pre-operatively not being
      associated with outcome, and very low-quality evidence supports other factors
      [pre-operative ODI, duration back pain, severity back pain, ipsilateral SLR and
      forward bend] not being associated with outcome [range of outcome measures used].
      CONCLUSION: An adequately powered low risk of bias prospective observational
      study is required to further investigate candidate physical prognostic factors
      owing to existing low/very-low level of evidence.

PMID- 30205813
TI  - Clinical outcomes of arthroscopic rotator cuff repair: a retrospective comparison
      of double-layer, double-row and suture bridge methods.
AB  - BACKGROUND: The suture-bridge (SB) method has recently become the mainstream
      means of repairing full-thickness rotator cuff tears. However, in some patients
      the deep and superficial layers have moved in different directions because of
      delamination of their rotator cuffs. In such cases, a simple suture (double
      layer, double-row [DD] method) is used to repair the superficial and deep layers
      separately. The purpose of this study was to analyze the clinical outcomes and re
      tear rates of the DD and SB methods, with patients selected according to the
      condition of their torn cuffs. METHODS: We retrospectively registered 74 patients
      with full-thickness rotator cuff tears that had been repaired arthroscopically,
      35 shoulders by the DD and 39 by the SB method. Mean ages were 66.1 years in the
      DD and 62.9 years in the SB group. We evaluated clinical status before and after
      surgery (Japanese Orthopedic Association [JOA] scores) and re-tear rate. The
      Wilcoxon signed-ranks test was used to compare JOA scores and active ROM between
      before and after surgery in each group. Mann-Whitney's U test was used for
      comparing JOA scores, active ROM, re-tear rates, size of tear, duration of follow
      up, sex, and presence of subscapular muscle repair between the DD and SB groups.
      A hazard ratio of less than 5% was considered to denote significance. RESULTS:
      JOA scores improved significantly in the DD and SB groups from preoperative means
      of 63.4 and 63.3 points, respectively, to postoperative means of 91.8 and 92.1
      points, respectively. The active flexural ROM improved significantly from means
      of 110.1 degrees  and 100.0 degrees , respectively, to postoperative means of
      142.3 degrees  and 142.7 degrees , respectively; the differences between groups
      were not significant. Re-tear occurred in 5.9% of the DD (two of 34 shoulders)
      and 7.9% of the SB group (three of 38 shoulders); its incidence did not differ
      significantly between the two groups. CONCLUSIONS: Both the DD and SB methods
      achieve satisfactory clinical outcomes that do not differ significantly. Our
      results suggest that careful selection of operative method on the basis of the
      delamination pattern in patients undergoing RCT may reduce the re-tear rate after
      utilizing the SB method.

PMID- 30205814
TI  - Correction to: Hand dexterity, not handgrip strength, is associated with
      executive function in Japanese community-dwelling older adults: a cross-sectional
      study.
AB  - ?.

PMID- 30205815
TI  - Correction to: Services according to mental health needs for youth in foster
      care? - a multi-informant study.
AB  - Following publication of the original article [1], the authors reported a
      misaligning of data in Table 3 (weekly results have been put in the column for
      monthly results).

PMID- 30205816
TI  - A study of anaesthesia-related cardiac arrest from a Chinese tertiary hospital.
AB  - BACKGROUND: The present survey evaluated the incidence of perioperative cardiac
      arrests in a Chinese tertiary general teaching hospital over ten years. METHODS:
      The incidence of cardiac arrest that occurred within 24 h of anaesthesia
      administration was retrospectively identified in the Third Affiliated Hospital of
      Sun Yat-Sen University between August 2007 and October 2017. Overall, 152,513
      anaesthetics were included in the study period. Data collected included patient
      characteristics, American Society of Anaesthesiologists (ASA) physical status
      score, surgical specialty and anaesthesia technique. Cardiac arrests were
      assigned to one of three groups: "anaesthesia-related", "anaesthesia
      contributing" or "anaesthesia-unrelated". RESULTS: In total, 104 cardiac arrests
      (6.8:10,000) and 34 deaths (2.2:10,000) were obtained. Among them, eleven cardiac
      arrests events were anaesthesia-related, resulting in an incidence of 0.7 per
      10,000 anaesthetics. Sixteen cardiac arrests events were found to be anaesthesia
      contributing, resulting in an incidence of 1.0 per 10,000 anaesthetics.
      Cardiovascular adverse events were the major events that contributed to
      anaesthesia-related cardiac arrest. Differences were found between events related
      and unrelated to anaesthesia with regard to ASA physical status and anaesthesia
      technique (P < 0.05). CONCLUSIONS: Anaesthesia-related cardiac arrest occurred in
      11 of 104 cardiac arrests within 24 h of anaesthesia administration. Most cardiac
      arrests related to anaesthesia were due to cardiovascular events, including
      arrhythmia and hypotension after intravenous narcotic, as well as haemorrhage.
      ASA physical status of at least 3 and subarachnoid block appeared to be relevant
      risk factors for anaesthesia-related cardiac arrest.

PMID- 30205817
TI  - The impacts of H. pylori virulence factors on the development of gastroduodenal
      diseases.
AB  - Although most H. pylori infectors are asymptomatic, some may develop serious
      disease, such as gastric adenocarcinoma, gastric high-grade B cell lymphoma and
      peptic ulcer disease. Epidemiological and basic studies have provided evidence
      that infection with H. pylori carrying specific virulence factors can lead to
      more severe outcome. The virulence factors that are associated with gastric
      adenocarcinoma development include the presence, expression intensity and types
      of cytotoxin-associated gene A (CagA, especially EPIYA-D type and multiple copies
      of EPIYA-C) and type IV secretion system (CagL polymorphism) responsible for its
      translocation into the host cells, the genotypes of vacuolating cytotoxin A
      (vacA, s1/i1/m1 type), and expression intensity of blood group antigen binding
      adhesin (BabA, low-producer or chimeric with BabB). The presence of CagA is also
      related to gastric high-grade B cell lymphoma occurrence. Peptic ulcer disease is
      closely associated with cagA-genopositive, vacA s1/m1 genotype, babA2
      genopositive (encodes BabA protein), presence of duodenal ulcer promoting gene
      cluster (dupA cluster) and induced by contact with epithelium gene A1 (iceA1),
      and expression status of outer inflammatory protein (OipA). The prevalence of
      these virulence factors is diverse among H. pylori isolated from different
      geographic areas and ethnic groups, which may explain the differences in disease
      incidences. For example, in East Asia where gastric cancer incidence is highest
      worldwide, almost all H. pylori isolates were cagA genopositive, vacA s1/i1/m1
      and BabA-expressing. Therefore, selection of appropriate virulence markers and
      testing methods are important when using them to determine risk of diseases. This
      review summarizes the evidences of H. pylori virulence factors in relation with
      gastroduodenal diseases and discusses the geographic differences and appropriate
      methods of analyzing these virulence markers.

PMID- 30205818
TI  - Predicting the outcome of conservative treatment with physiotherapy in adults
      with shoulder pain associated with partial-thickness rotator cuff tears - a
      prognostic model development study.
AB  - BACKGROUND: Rotator cuff disorders represent the commonest type of painful
      shoulder complaints in clinical practice. Although conservative treatment
      including physiotherapy is generally recommended as first-line treatment, little
      is known about the precise treatment indications for subgroups of rotator cuff
      disorders, particularly people with shoulder pain associated with partial
      thickness tears of the rotator cuff, PTTs: "symptomatic PPTs". The aim of this
      study was to develop a prognostic model for predicting the outcome of a phase of
      conservative treatment primarily with physiotherapy in adults with symptomatic
      PTTs. METHODS: A prospective observational cohort study was conducted in an
      outpatient setting in Germany. Ten baseline factors were selected to evaluate
      nine pre-defined multivariable candidate prognostic models (each including
      between two and nine factors) in a cohort of adults with symptomatic atraumatic
      PTTs undergoing a three-month phase of conservative treatment primarily with
      physiotherapy. The primary outcome was change in the Western Ontario Rotator Cuff
      Index. The models were developed using linear regression and an information
      theoretic analysis approach: Akaike's Information Criterion (AICC). RESULTS:
      Eight candidate models were analyzed using data from 61 participants. Two "best
      models" were identified: smoking & pain catastrophizing and disability & pain
      catastrophizing. However, none of the models had a satisfactory performance or
      precision. CONCLUSIONS: We could not determine a prognostic model with
      satisfactory performance and precision. Further high-quality prognostic model
      studies with larger samples are needed, but should be underpinned, and thus
      preceded, by robust research that enhances knowledge of relevant prognostic
      factors. STUDY REGISTRATION: DRKS00004462 . Registered 08 April 2014;
      retrospectively registered (prior to the analysis).

PMID- 30205819
TI  - Factors influencing the use of clinical guidelines by general practitioners
      working in a setting of complex multimorbidity: a case study by interviews.
AB  - BACKGROUND: The Central Australian Remote Practitioners Association Standard
      Treatment Manual (CARPA) contains protocols for primary health care in remote
      Central Australia. This context stands in stark contrast to the mainstream
      settings in Australia and features an Aboriginal population with very poor health
      status, powerful social determinants of health, geographical isolation and high
      turnover of health practitioners. The manual consolidates the core elements of
      national guidelines, particularly as they pertain to Aboriginal health care, into
      a single document. The aim of this study is to explore factors that promote or
      impede the use of CARPA by general practitioners (GPs) in Central Australia, with
      a particular focus on chronic disease management. METHODS: In-depth interviews
      were conducted with GPs and GP registrars employed in the provision of Aboriginal
      health care in Central Australia. Interview transcripts were thematically
      analysed from a critical theory perspective. RESULTS: 11 GPs and 3 GP registrars
      from the two major Aboriginal primary health services in Central Australia were
      interviewed. The dominant theme in the data was that poor continuity of care
      impeded the use of CARPA. The second-most dominant theme was that electronic
      health record systems enhanced the use of CARPA in some ways, and impeded its use
      in others. Other factors influencing the use of CARPA included the culture of the
      health service organisation, GPs' first impressions of CARPA, the accessibility
      and usability of CARPA, and GPs' confidence practicing in such a unique
      environment. CONCLUSIONS: This study identifies factors from multiple domains
      that influence the use of best practice guidelines in the delivery of chronic
      disease care. It demonstrates that such factors may not be purely 'enablers' or
      'barriers', but may be a mixture of both. It highlights the critical role of
      continuity of care and the potential benefits and pitfalls of using electronic
      health records in providing chronic disease care. This study provides empirical
      insights that can be used to improve chronic disease care.

PMID- 30205820
TI  - Protein fishing from single live cells.
AB  - Intracellular protein and proteomic studies using mass spectrometry, imaging
      microscopy, flow cytometry, or western blotting techniques require genetic
      manipulation, cell permeabilization, and/or cell lysis. We present a biophysical
      method that employs a nanoaspirator to 'fish' native cytoplasmic or nuclear
      proteins from single mammalian cells, without compromising cell viability,
      followed by ex cellulo quantitative detection. Our work paves the way for
      spatiotemporally-controlled, quantitative, live, single-cell proteomics.

PMID- 30205821
TI  - A micro-/nano-chip and quantum dots-based 3D cytosensor for quantitative analysis
      of circulating tumor cells.
AB  - BACKGROUND: Due to the high transfer ability of cancer cell, cancer has been
      regarded as a world-wide high mortality disease. Quantitative analysis of
      circulating tumor cells (CTCs) can provide some valuable clinical information
      that is particularly critical for cancer diagnosis and treatment. Along with the
      rapid development of micro-/nano-fabrication technique, the three-dimensional
      (3D) bionic interface-based analysis method has become a hot research topic in
      the area of nanotechnology and life science. Micro-/nano-structure-based devices
      have been identified as being one of the easiest and most effective techniques
      for CTCs capture applications. METHODS: We demonstrated an electrospun nanofibers
      deposited nickel (Ni) micropillars-based cytosensor for electrochemical detection
      of CTCs. Breast cancer cell line with rich EpCAM expression (MCF7) were selected
      as model CTCs. The ultra-long poly (lactic-co-glycolic acid) (PLGA) nanofibers
      were firstly-crosswise stacked onto the surface of Ni micropillars by
      electrospinning to construct a 3D bionic interface for capturing EpCAM-expressing
      CTCs, following immuno-recognition with quantum dots functionalized anti-EpCAM
      antibody (QDs-Ab) and forming immunocomplexes on the micro-/nano-chip. RESULTS:
      The Ni micropillars in the longitudinal direction not only play a certain
      electrical conductivity in the electrochemical detection, but also its special
      structure improves the efficiency of cell capture. The cross-aligned nanofibers
      could simulate the extracellular matrix to provide a good microenvironment which
      is better for cell adhesion and physiological functions. Bioprobe containing
      quantum dots will release Cd2+ in the process of acid dissolution, resulting in a
      change in current. Beneath favourable conditions, the suggested 3D cytosensor
      demonstrated high sensitivity with a broad range of 101-105 cells mL-1 and a
      detection limit of 8 cells mL-1. CONCLUSIONS: We constructed a novel 3D
      electrochemical cytosensor based on Ni micropillars, PLGA electrospun nanofibers
      and quantum dots bioprobe, which could be used to highly sensitive and selective
      analysis of CTCs. More significantly, the 3D cytosensor can efficiently identify
      CTCs from whole blood, which suggested the potential applications of our
      technique for the clinical diagnosis and therapeutic monitoring of cancers.

PMID- 30205823
TI  - Intraoperative ultrasound in breast cancer surgery-from localization of non
      palpable tumors to objectively measurable excision.
AB  - BACKGROUND: The utilization of intraoperative ultrasound (IOUS) in breast cancer
      surgery is a relatively new concept in surgical oncology. Over the last few
      decades, the field of breast cancer surgery has been striving for a more rational
      approach, directing its efforts towards removing the tumor entirely yet sparing
      tissue and structures not infiltrated by tumor cells. Further progress in
      objectivity and optimization of breast cancer excision is possible if we make the
      tumor and surrounding tissue visible and measurable in real time, during the
      course of the operation; IOUS seems to be the optimal solution to this complex
      requirement. IOUS was introduced into clinical practice as a device for
      visualization of non-palpable tumors, and compared to wire-guided localization
      (WGL), IOUS was always at least a viable, or much better alternative, in terms of
      both precision in identification and resection and for patients' and surgeons'
      comfort. In recent years, intraoperative ultrasound has been used in the surgery
      of palpable tumors to optimize resection procedures and overcome the
      disadvantages of classic palpation guided surgery. OBJECTIVE: The aim of this
      review is to show the role of IOUS in contemporary breast cancer surgery and its
      changes over time. METHODS: A PubMed database comprehensive search was conducted
      to identify all relevant articles according to assigned key words. CONCLUSION:
      Over time, the use of IOUS has been transformed from being the means of
      localizing non-palpable lesions to an instrument yielding a reduced number of
      positive resection margins, with a smaller volume of healthy breast tissue
      excided around tumor, by making the excision of the tumor optimal and objectively
      measurable.

PMID- 30205822
TI  - Pluronic-based nano-self-assemblies of bacitracin A with a new mechanism of
      action for an efficient in vivo therapeutic effect against bacterial peritonitis.
AB  - BACKGROUND: Although assemblies of hydrophobic-modified bacitracin A with PLGA
      (Nano-BAPLGA) have demonstrated promising antibacterial activities against both
      Gram-positive and Gram-negative bacteria, the desirable antibacterial potency has
      remained challenging due to the low solubility of Nano-BAPLGA. To address this
      tissue, a series of Pluronic copolymers (Pluronic(r) F127, Pluronic(r) P123 and
      Pluronic(r) P85) were selected to link the N-terminus of bacitracin A to
      construct Pluronic-based nano-self assemblies (Nano-BAF127, Nano-BAP123 and Nano
      BAP85). RESULTS: Impressively, all the newly designed Pluronic-based Nano-BAs
      possessed higher solubility and stronger effectiveness against both Gram-positive
      and Gram-negative bacteria compared with Nano-BAPLGA, especially the modification
      with Pluronic(r) P85. Surface tension measurements indicated that Nano-BAP85 was
      much more tensioactive than Nano-BAPLGA, which usually translated into a good
      membranolytic effect. Fluorescence spectroscopy and electron microscopy analyses
      confirmed the speculation that the cell wall/membrane might be the main action
      target of Nano-BAP85 by permeabilizing the cell membrane and damaging the
      membrane integrity. In vivo results further demonstrated that Nano-BAP85
      significantly suppressed bacterial growth and prolonged survival time in the
      bacterial peritonitis mouse model with negligible toxicity. CONCLUSIONS:
      Collectively, the membrane targeting mechanism of action is entirely distinct
      from those of clinically used antibacterial agents. Furthermore, the new approach
      of construction nanoantibiotics based on the modification of commercially
      available antibiotics with Pluronic copolymers is demonstrated to have an
      efficient therapeutic effect against bacterial infection.

PMID- 30205824
TI  - Regulation of calcitonin gene-related peptide expression through the COX-2/mPGES
      1/PGE2 pathway in the infrapatellar fat pad in knee osteoarthritis.
AB  - BACKGROUND: The infrapatellar fat pad (IFP) is implicated in knee osteoarthritis
      (KOA). Calcitonin gene-related peptide (CGRP), a vasoactive neuropeptide
      expressed in joint tissues and synovial tissues (ST), was recently found to be
      associated with KOA progression and pain. CGRP is expressed in the IFPs of human
      KOA patients; however, its regulation has not been elucidated. METHODS: IFPs and
      STs were harvested from 138 KOA patients during total knee replacement (TKR) and
      analyzed for CGRP, cycloxygenase-2 (COX-2), and microsomal prostaglandin E
      synthase-1 (mPGES-1) expression using real-time polymerase chain reaction (PCR).
      To investigate CGRP regulation by prostaglandin E2 (PGE2), adipocytes (Ad) and
      the stromal vascular fraction (SVF) were harvested from IFPs using collagenase.
      Synovial cells (SYC) were also harvested from ST and stimulated with vehicle
      (serum-free culture medium), PGE2, or CGRP. RESULTS: CGRP, COX-2, and mPGES-1
      expression levels were significantly higher in IFPs than STs. PGE2 stimulation
      increased CGRP expression in Ad, the SVF, and SYC; however, CGRP expression was
      significantly higher in PGE2-stimulated SVF than PGE2-stimulated SYC. CGRP
      stimulation had no effect on COX-2 or mPGES-1 expression. CONCLUSIONS: CGRP
      expression in the IFP of KOA patients is regulated by the COX-2/mPGES-1/PGE2
      pathway.

PMID- 30205826
TI  - We should avoid the term "fluid overload".

PMID- 30205825
TI  - Promoting the use of self-management in novice chiropractors treating individuals
      with spine pain: the design of a theory-based knowledge translation intervention.
AB  - BACKGROUND: Clinical practice guidelines generally recommend clinicians use self
      management support (SMS) when managing patients with spine pain. However, even
      within the educational setting, the implementation of SMS remains suboptimal. The
      objectives of this study were to 1) estimate the organizational readiness for
      change toward using SMS at the Canadian Memorial Chiropractic College (CMCC),
      Toronto, Ontario from the perspective of directors and deans, 2) estimate the
      attitudes and self-reported behaviours towards using evidence-based practice
      (EBP), and beliefs about pain management among supervisory clinicians and
      chiropractic interns, 3) identify potential barriers and enablers to using SMS,
      and 4) design a theory-based tailored Knowledge Translation (KT) intervention to
      increase the use of SMS. METHODS: Mixed method design. We administered three self
      administered questionnaires to assess clinicians' and interns' attitudes and
      behaviours toward EBP, beliefs about pain management, and practice style. In
      addition, we conducted 3 focus groups with clinicians and interns based on the
      Theoretical Domain Framework (TDF) to explore their beliefs about using SMS for
      patients with spine pain. Data were analysed using deductive thematic analysis by
      2 independent assessors. A panel of 7 experts mapped behaviour change techniques
      to key barriers identified informing the design of a KT intervention. RESULTS:
      Participants showed high level of EBP knowledge, positive attitude of EBP, and
      moderate frequency of EBP use. A number of barrier factors were identified from
      clinicians (N = 6) and interns (N = 16) corresponding to 7 TDF domains:
      Knowledge; Skills; Environmental context and resources; Emotion; Beliefs about
      Capabilities; Memory, attention & decision making; and Social Influence. To
      address these barriers, the expert panel proposed a multifaceted KT intervention
      composed of a webinar and online educational module on a SMS guided by the Brief
      Action Planning, clinical vignettes, training workshop, and opinion leader
      support. CONCLUSION: SMS strategies can help maximizing the health care services
      for patients with spine pain. This may in turn optimize patients' health. The
      proposed theory-based KT intervention may facilitate the implementation of SMS
      among clinicians and interns.

PMID- 30205827
TI  - Modified Lemaire extra-articular stabilisation of the knee for the treatment of
      anterolateral instability combined with diffuse pigmented villonodular synovitis:
      a case report.
AB  - BACKGROUND: Diffuse pigmented villonodular synovitis (PVNS) of the knee is a rare
      proliferative joint disease associated with high recurrence rates following
      surgical treatment. Intra-articular joint instability in conjunction with PVNS
      implies complex reconstructive strategies due to the destructive nature of the
      disease. CASE PRESENTATION: Here, we present the case of a young patient with
      refractory PVNS and a chronic ipsilateral anterior cruciate ligament (ACL)
      rupture. Clinically, the patient presented with a grade 3 pivot shift phenomenon,
      indicating anterolateral rotational instability. Usually, PVNS implies a
      contraindication for ACL reconstruction due to the degenerative and pro
      inflammatory joint microenvironment that is induced and maintained by PVNS.
      Therefore, we have performed a modified Lemaire extra-articular stabilization
      resulting in significant clinical improvement and subjective joint stability. In
      the latest follow-up examination at 12 months, the patient reported subjective
      joint stability and no swelling. In the clinical examination, the patient showed
      dynamic joint stability during walking. Additionally, the patient presented with
      grade 0 in pivot-shifting compared to the contralateral knee. The Lachman test
      exhibited no increased side-to-side difference and a firm endpoint. CONCLUSIONS:
      Extra-articular anterolateral stabilisation of the knee in patients having
      anterolateral knee instability combined with PVNS is a safe and efficient
      surgical treatment option yielding significant clinical improvement as well as
      subjective joint stability.

PMID- 30205829
TI  - Correction to: Non-communicable disease prevention policy process in five African
      countries.
AB  - After publication of the article [1], it was noticed that the title has
      erroneously included 'authors' in the end.

PMID- 30205831
TI  - Immunological and morphological analysis of heterotopic ossification differs to
      healthy controls.
AB  - BACKGROUND: Formation of lamellar bone in non-osseus tissue is a pathological
      process called heterotopic ossification. It is the aim of this study to analyse
      the morphology and immunological status of patients with heterotopic ossification
      compared to individual healthy persons. METHODS: Human bone marrow and blood
      samples were obtained from 6 systemically healthy individuals and 4 patients
      during resection of heterotopic ossification from bone at hip arthroplasty. Bone
      was fragmented and treated with purified collagenase. Immunofluorescence surface
      staining was performed and analyzed with flow cytometry. Microcomputed tomography
      scanning was done performed at a resolution of 11 and 35 MUm isometric voxel size
      respectively using a two different cone beam X-computer tomography systems and a
      microfocus X-ray tube. Subsequently the volume data was morphometrically
      analysed. RESULTS: The monocytes, stem cells, stroma cells and granulocytes
      progenitor cells were strongly reduced in the heterotopic ossification patient.
      Additionally a significant reduction of stromal stem cells cells and CD34
      positive stem cells was observed. The frequency of NK-cells, B cells and T cells
      were not altered in the patients with heterotopic ossification compared to a
      healthy person. Micromorphometric parameters showed a lower content of
      mineralized bone tissue compared to normal bone. Mean trabecular thickness showed
      a high standard deviation, indicating a high variation in trabecular thickness,
      anisotropy and reducing bone strength. CONCLUSIONS: This work shows altered
      immunological distribution that is accompanied by a low decrease in bone volume
      fraction and tissue mineral density in the heterotopic ossification sample
      compared to normal bone. Compared to healthy subjects, this might reflect an
      immunological participation in the development of this entity.

PMID- 30205832
TI  - The impact of chronic disease management on primary care doctors in Switzerland:
      a qualitative study.
AB  - BACKGROUND: Patient-centeredness and therapeutic relationship are widely explored
      as a means to address the challenge of chronic disease and multi-morbidity
      management, however research focusing on the perspective of doctors is still
      rare. In this study, we aimed to explore the impact of the patient's chronic
      disease(s) on their healthcare provider. METHODS: A qualitative approach was
      taken using semi-structured interviews with general practitioners working in
      outpatient clinics either in individual practices or in a hospital setting in
      Geneva, Switzerland. Codes were developed through an iterative process and using
      grounded theory an inductive coding scheme was performed to identify the key
      themes. Throughout the analysis process the research team reviewed the analysis
      and refined the coding scheme. RESULTS: Twenty interviews, 10 in each practice
      type, allowed for saturation to be reached. The following themes relevant to the
      impact of managing chronic diseases emerge around the issue of feeling powerless
      as a doctor; facing the patient's socio-economic context; guidelines versus the
      reality of the patient; time; and taking on the patient's burden. Primary care
      practitioners face an emotional burden linked with their powerlessness and work
      conditions, but also with the empathetic bond with their patients and their
      circumstances. Doctors seem poorly prepared for this emotional strain. The health
      system is also not facilitating this with time constraints and guidelines
      unsuitable for the patient's reality. CONCLUSIONS: Chronic disease and multi
      morbidity management is a challenge for healthcare providers. This has its roots
      in patient characteristics, the overall health system and healthcare providers
      themselves. Structural changes need to be implemented at different levels:
      medical education; health systems; adapted guidelines; leading to an overall
      environment that favors the development of the therapeutic relationship.

PMID- 30205830
TI  - Improving mental health through integration with primary care in rural Karnataka:
      study protocol of a cluster randomized control trial.
AB  - BACKGROUND: People who are diagnosed with both mental and chronic medical illness
      present unique challenges for the health care system. In resource-limited
      settings, such as rural India, people with depression and anxiety are often under
      served, due to both stigma and lack of trained providers and resources. These
      challenges can lead to complications in the management of chronic disease as well
      as increased suffering for patients, families and communities. In this study, we
      evaluate the effects of integrating mental health and chronic disease treatment
      of patients in primary health care (PHC) settings using a collaborative care
      model to improve the screening, diagnosis and treatment of depression in rural
      India. METHODS: This study is a multi-level randomized controlled trial among
      patients with depression or anxiety and co-morbid diabetes, or cardiovascular
      disease. Aim 1 examines whether patients screened at community health-fairs are
      more likely to be diagnosed and treated for these co-morbid conditions than
      patients screened after presenting at PHCs. Aim 2 evaluates the impact of
      collaborative care compared to usual care in a cluster RCT, randomizing at the
      level of the PHCs. Intervention arm PHC staff are trained in mental health
      diagnoses, treatment, and the collaborative care model. The intervention also
      involves community-based "Healthy Living groups" co-led by Ashas, using cognitive
      behavioral strategies to promote healthy behaviors. The primary outcome is
      severity of common mental disorders, with secondary outcomes being diabetes and
      cardiovascular risk, staff knowledge and patient perceptions. DISCUSSION: If
      effective, our results will contribute to the field in five ways: 1) expand on
      implementation research in low resource settings by examining how multiple
      chronic diseases can be treated using integrated low-cost, evidence-based
      strategies, 2) build the capacity of PHC staff to diagnose and treat mental
      illness within their existing clinic structure and strengthen referral linkages;
      3) link community members to primary care through community-based health fairs
      and healthy living groups; 4) increase mental health awareness in the community
      and reduce mental health stigma; 5) demonstrate the potential for intervention
      scale-up and sustainability. TRIAL REGISTRATION: http://Clinicaltrials.gov :
      NCT02310932 registered December 8, 2014 URL:
      https://clinicaltrials.gov/ct2/show/record/NCT02310932 ; Clinical Trials Registry
      India: CTRI/2018/04/013001 retrospectively registered on April 4, 2018.

PMID- 30205833
TI  - Expression of HMB45, MelanA and SOX10 is rare in non-small cell lung cancer.
AB  - BACKGROUND: Non-small cell lung cancer (NSCLC) and melanoma are frequent entities
      in routine diagnostics. Whereas the differential diagnosis is usually straight
      forward based on histomorphology, it can be challenging in poorly differentiated
      tumors as melanoma may mimic various histological patterns. Distinction of the
      two entities is of outmost importance as both are treated differently. HMB45 and
      MelanA are recommended immunohistological markers for melanoma in this scenario.
      SOX10 has been described as an additional marker for melanoma. However,
      comprehensive large-scale data about the expression of melanoma markers in NSCLC
      tumor tissue specimen are lacking so far. METHODS: Therefore, we analyzed the
      expression of these markers in 1085 NSCLC tumor tissue samples. Tissue
      microarrays of NSCLC cases were immunohistochemically stained for HMB45, MelanA,
      and SOX10. Positivity of a marker was defined as >=1% positive tumor cells.
      RESULTS: In 1027 NSCLC tumor tissue samples all melanoma as well as conventional
      immunohistochemical markers for NSCLC could be evaluated. HMB45, MelanA, and
      SOX10 were positive in 1 (< 1%), 0 (0%) and 5 (< 1%) cases. The HMB45 positive
      case showed co-expression of SOX10 and was classified as large cell carcinoma.
      Three out of five SOX10 positive cases were SqCC and one case was an
      adenosquamous carcinoma. CONCLUSIONS: Expression of HMB45, MelanA and SOX10 is
      evident but exceedingly rare in NSCLC cases. Together with conventional
      immunomarkers a respective marker panel allows a clear-cut differential diagnosis
      even in poorly differentiated tumors.

PMID- 30205828
TI  - Reactive oxygen species and male reproductive hormones.
AB  - Reports of the increasing incidence of male infertility paired with decreasing
      semen quality have triggered studies on the effects of lifestyle and
      environmental factors on the male reproductive potential. There are numerous
      exogenous and endogenous factors that are able to induce excessive production of
      reactive oxygen species (ROS) beyond that of cellular antioxidant capacity, thus
      causing oxidative stress. In turn, oxidative stress negatively affects male
      reproductive functions and may induce infertility either directly or indirectly
      by affecting the hypothalamus-pituitary-gonadal (HPG) axis and/or disrupting its
      crosstalk with other hormonal axes. This review discusses the important exogenous
      and endogenous factors leading to the generation of ROS in different parts of the
      male reproductive tract. It also highlights the negative impact of oxidative
      stress on the regulation and cross-talk between the reproductive hormones. It
      further describes the mechanism of ROS-induced derangement of male reproductive
      hormonal profiles that could ultimately lead to male infertility. An
      understanding of the disruptive effects of ROS on male reproductive hormones
      would encourage further investigations directed towards the prevention of ROS
      mediated hormonal imbalances, which in turn could help in the management of male
      infertility.

PMID- 30205834
TI  - Inhibition of NF-kappaB in astrocytes is sufficient to delay neurodegeneration
      induced by proteotoxicity in neurons.
AB  - BACKGROUND: Most neurodegenerative diseases associated with protein aggregation
      are hallmarked by activation of astrocytes. However, how astrocytes are activated
      or which signaling pathways in astrocytes contribute to pathogenesis is not
      clear. One long-standing question is whether the responses in astrocytes are due
      to stress or damage in astrocytes themselves, or because of astrocytic responses
      to cellular stress or damage in neurons. Here, we examine responses in astrocytes
      induced by expression of disease-associated, aggregation-prone proteins in other
      cells. We also examine the consequences of these responses in astrocytes in a
      model for neurodegeneration. METHODS: We first examined a role for intracellular
      astrocytic responses in a Drosophila model for Spinocerebellar ataxia type 3
      (SCA3, also known as Machado-Joseph disease), a disease caused by expansion of
      the polyglutamine (polyQ) stretch in the ATXN3 gene. In this Drosophila SCA3
      model, eye-specific expression of a biologically relevant portion of the ATXN3
      gene, containing expanded polyQ repeats (SCA3polyQ78) was expressed. In a
      candidate RNAi screen in the Drosophila SCA3 model, we analyzed whether
      downregulation of expression of specific genes in astrocytes affected
      degeneration induced by SCA3polyQ78 expression in Drosophila eyes. We next
      examined the role of astrocytes in response to proteotoxic stress in neurons
      induced by SCA3polyQ78 expression or amyloid beta peptides, associated with
      Alzheimer's disease. RESULTS: Eye-specific expression of SCA3polyQ78 resulted in
      the presence of astrocytes in the eye, suggesting putative involvement of
      astrocytes in SCA3. In a candidate RNAi screen, we identified genes in astrocytes
      that can enhance or suppress SCA3polyQ78-induced eye degeneration. Relish, a
      conserved NF-kappaB transcription factor, was identified as an enhancer of
      degeneration. Activity of Relish was upregulated in our SCA3 model. Relish can
      exert its effect via Relish-specific AMPs, since downregulation of these AMPs
      attenuated degeneration. We next examined Relish signaling in astrocytes on
      neurodegeneration. Selective inhibition of Relish expression specifically in
      astrocytes extended lifespan of flies that expressed SCA3polyQ78 exclusively in
      neurons. Inhibition of Relish signaling in astrocytes also extended lifespan in a
      Drosophila model for Alzheimer's disease. CONCLUSIONS: Our data demonstrate that
      astrocytes respond to proteotoxic stress in neurons, and that these astrocytic
      responses are important contributors to neurodegeneration. Furthermore, our data
      demonstrate that activation of NF-kappaB transcription factor Relish in
      astrocytes, induced by proteotoxic stress in neurons, enhances neurodegeneration,
      and that specific Relish inhibition in astrocytes extends lifespan. Our data
      provide direct evidence for cell-non-autonomous contributions of astrocytes to
      neurodegeneration, with possible implications for therapeutic interventions in
      multiple neurodegenerative diseases.

PMID- 30205835
TI  - Massive increase in monocyte HLA-DR expression can be used to discriminate
      between septic shock and hemophagocytic lymphohistiocytosis-induced shock.

PMID- 30205836
TI  - The prevalence and associated factors of symptomatic cervical Spondylosis in
      Chinese adults: a community-based cross-sectional study.
AB  - BACKGROUND: Cervical spondylosis adversely affects life quality for its heavy
      disease burden. The report on the community-based prevalence and associated
      factors of cervical spondylosis is rare, especially in Chinese population.
      Whether prevention is needed and how to prevent it is not clear. This study aims
      to explore its prevalence and related lifestyle factors and provide evidence on
      prevention of cervical spondylosis. METHODS: A community-based multistage cross
      sectional survey of six communities from the Chinese population was conducted. A
      face-to-face interview was conducted to obtain individual information, and
      prevalence was calculated. Single-factor analysis and multivariable logistic
      regressions were used to explore the associated factors in total and subgroup
      populations. RESULTS: A total of 3859 adults were analyzed. The prevalence of
      cervical spondylosis was 13.76%, although it differed significantly among the
      urban, suburban, and rural populations (13.07%, 15.97%, and 12.25%,
      respectively). Moreover, it was higher in females than in males (16.51% vs
      10.49%). The prevalence among different age groups had an inverted U shape. The
      highest prevalence was in the age group from 45 to 60 years old. The associated
      factors differed by subgroups. There were positive associations between engaging
      in mental work, high housework intensity, and sleep duration of less than 7 h/day
      with cervical spondylosis. Going to work on foot was a negative factor of
      cervical spondylosis in the total population. For people aged less than 30 years,
      keeping the same work posture for 1-2.9 h/day was a special related factor.
      Exposure to vibration was an associated factor for females aged 45-60 years.
      Menopause was a special related factor for women. CONCLUSIONS: Prevalence of
      cervical spondylosis was high in Chinese population. People younger than 60 years
      were the focus of prevention for cervical spondylosis. Moreover, the characters
      between male and female and among different age groups were different and
      required targeted interventions.

PMID- 30205837
TI  - Evaluation of preoperative anxiety and fear of anesthesia using APAIS score.
AB  - BACKGROUND: Preoperative anxiety is one of the most important problems for the
      patients, because it causes emotional and psychiatric problems as well as
      physical problems. It is crucial to detect the patient's existing anxiety to
      assist patients. Our primary aim in this study is to investigate how the
      patient's age, gender, the operation, surgical briefing, type of anesthesia
      recommended for the operation ahead, and patient's prior anesthesia experience
      affect the patient's anxieties. Our secondary aim is to reveal the causes of the
      patient's anxieties regarding anesthesia. METHODS: Our study was conducted as a
      prospective cohort study between May 2016-2017. Interviews with the patients were
      performed in the anesthesia clinic for preoperative examination. For the study,
      The Amsterdam Preoperative Anxiety and Information Scale (APAIS) has been used.
      The answers were evaluated in two scales: the anxiety score and the desire for
      information score. Answers to the statements were evaluated with Likert Scale. In
      addition, our patients were asked whether they had received prior anesthesia, if
      so, the type of anesthesia, whether they received surgical briefing and
      anesthetic method we recommended. We also asked our patients about the cause of
      their anxiety regarding the anesthesia. RESULTS: A total of 637 patients were
      recruited to the study, after excluding the patients who do not meet the criteria
      for inclusion, and 499 patients were included. Between the age and desire for
      information sub-scores, a negative significant correlation was detected (r: -
      0.241; p = 0.001). We found that the scores of graduates of university and higher
      were statistically significant than the primary school graduates (p = 0.003) and
      secondary school graduates (p = 0.034). Anxiety sub-scores of the patients who
      underwent general anesthesia were found to be significantly higher than the
      patients who underwent regional anesthesia (p = 0.029). Anxiety sub-scores of
      females were found to be significantly higher than the males (p = 0.001).
      CONCLUSIONS: We think that being aware of the patients' anxiety and finding
      appropriate approaches for their anxieties can be valuable. APAIS is an effective
      method to measure patient anxiety and it might be beneficial to use during
      preoperative visits. Patient satisfaction and superior outcomes can be achieved
      in this way. Trial registration ISRCTN43960422. Registered 19/02/2018
      Retrospectively registered. http://www.isrctn.com/ISRCTN43960422.

PMID- 30205838
TI  - Is intracranial volume a suitable proxy for brain reserve?
AB  - BACKGROUND: Brain reserve is a concept introduced to explain why Alzheimer's
      disease (AD) patients with a greater brain volume prior to onset of pathology
      generally have better clinical outcomes. In this review, we provide a historical
      background of the emergence of brain reserve and discuss several aspects that
      need further clarification, including the dynamic or static nature of the concept
      and its underlying mechanisms and clinical effect. We then describe how brain
      reserve has been operationalized over the years, and critically evaluate the use
      of intracranial volume (ICV) as the most widely used proxy for brain reserve.
      Furthermore, we perform a meta-analysis showing that ICV is associated with
      higher cognitive performance after adjusting for the presence and amount of
      pathology. Although we acknowledge its imperfections, we conclude that the use of
      ICV as a proxy for brain reserve is currently warranted. However, further
      development of more optimal measures of brain reserve as well as a more clearly
      defined theoretical framework is essential.

PMID- 30205839
TI  - Cancer expression quantitative trait loci (eQTLs) can be determined from
      heterogeneous tumor gene expression data by modeling variation in tumor purity.
AB  - Expression quantitative trait loci (eQTLs) identified using tumor gene expression
      data could affect gene expression in cancer cells, tumor-associated normal cells,
      or both. Here, we have demonstrated a method to identify eQTLs affecting
      expression in cancer cells by modeling the statistical interaction between
      genotype and tumor purity. Only one third of breast cancer risk variants,
      identified as eQTLs from a conventional analysis, could be confidently attributed
      to cancer cells. The remaining variants could affect cells of the tumor
      microenvironment, such as immune cells and fibroblasts. Deconvolution of tumor
      eQTLs will help determine how inherited polymorphisms influence cancer risk,
      development, and treatment response.

PMID- 30205841
TI  - A comparative study on the validity and reliability of anterior, medial, and
      posterior approaches for internal fixation in the repair of fractures of the
      coronoid process of the ulna.
AB  - BACKGROUND: The coracoid process plays an important role in maintaining the
      stability of the elbow joint. A fracture of the coronoid process is often treated
      via surgical approaches, including open reduction and internal fixation, which
      aim to regain a stable, flexible, and loadable joint. In this study, we compared
      the anterior, medial, and posterior approaches of internal fixation in the repair
      of fractures of the coronoid process of the ulna. METHODS: In this retrospective
      study, 147 patients with fractures in the coronoid process of the ulna were
      recruited and classified into the anterior group (n = 73), the medial group (n =
      32), and the posterior group (n = 42) according to the surgical approach used for
      internal fixation. These patients were assessed with respect to incision,
      operative time, estimated blood loss, fracture healing, and postoperative
      complications. The Mayo Elbow Performance Score was used to evaluate any form of
      disability associated with elbow injuries. Multivariate logistic regression
      analysis was performed to investigate the factors influencing the efficacy of
      fractures of the coronoid process of the ulna. RESULTS: In the medial approach
      group, the operative time was longer, and perioperative blood loss and
      postoperative drainage volume were obviously increased compared with the anterior
      and posterior groups. The anterior group exhibited a better postoperative
      recovery compared with the medial, and posterior groups. Compared with the
      anterior group, fracture-healing time in the posterior group was further reduced,
      whereas elbow joint flexion extension and forearm rotation degree improved.
      Complications were significantly reduced in the posterior approach group compared
      with the anterior and medial groups. The factors influencing the efficacy of
      fractures of the coronoid process of the ulna included the Regan-Morrey
      classification, perioperative blood loss, and the internal fixation approach.
      CONCLUSION: In summary, the approach used influences fracture healing or the
      outcome after osteosynthesis. The posterior internal fixation method produced
      satisfactory functional outcomes in patients with fractures of the coronoid
      process of the ulna.

PMID- 30205840
TI  - Cognitive composite score association with Alzheimer's disease plaque and tangle
      pathology.
AB  - BACKGROUND: Cognitive composite scores are used as the primary outcome measures
      for Alzheimer's disease (AD) prevention trials; however, the extent to which
      these composite measures correlate with AD pathology has not been fully
      investigated. Since many on-going AD prevention studies are testing therapies
      that target either amyloid or tau, we sought to establish an association between
      a cognitive composite score and the underlying pathology of AD. METHODS: Data
      from 192 older deceased and autopsied persons from the Rush Religious Order Study
      were used in this study. All participants were classified at their initial
      evaluations with a clinical diagnosis of no cognitive impairment (NCI). Of these
      individuals, 105 remained NCI at the time of their death while the remaining 87
      progressed to mild cognitive impairment (MCI) or AD. A cognitive composite score
      composed of eight cognitive tests was used as the outcome measure. Individuals
      were classified into groups based on Consortium to Establish a Registry for
      Alzheimer's Disease (CERAD) neuropathological diagnosis and Braak stage. RESULTS:
      The rate of annualized composite score decline was significantly greater for the
      high CERAD (p < 0.001, d = 0.56) and Braak (p < 0.001, d = 0.55) groups compared
      with the low CERAD and Braak groups, respectively. Mixed-model repeated measure
      (MMRM) analyses revealed a significantly greater difference in composite score
      change from baseline for the high CERAD group relative to the low CERAD group
      after 5 years (Delta = -2.74, 95% confidence interval (CI) -5.01 to -0.47; p =
      0.02). A similar analysis between low and high Braak stage groups found no
      significant difference in change from baseline (Delta = -0.69, 95% CI -3.03 to
      1.66; p = 0.56). CONCLUSIONS: These data provide evidence that decreased
      cognitive composite scores were significantly associated with increased AD
      pathology and provide support for the use of cognitive composite scores in AD
      prevention trials.

PMID- 30205842
TI  - The sustainability of Lean in pediatric healthcare: a realist review.
AB  - BACKGROUND: Lean is a quality improvement management system from the Toyota
      manufacturing industry. Since the early 2000's, Lean has been used as an
      intervention for healthcare improvement. Lean is intended to reduce costs and
      improve customer value through continuous improvement. Despite its extensive use,
      the contextual factors and mechanisms that influence the sustainability of Lean
      in healthcare have not been well studied. Realist synthesis is one approach to
      "unpack" the causal explanations of how and why Lean is sustained or not in
      healthcare. We conducted a realist synthesis using the context (C) + mechanim (M)
      = outcome (O) heuristic, to further develop and refine an initial program theory
      with seven CMO hypotheses, on the sustainability of Lean efforts across pediatric
      healthcare. METHODS: Our search strategy was multi-pronged, iterative, and
      purposeful in nature, consisting of database, gray literature, and contact with
      three healthcare organizations known for Lean implementation. We included primary
      research studies, published and unpublished case studies or reports, if they
      included Lean implementation with a pediatric focus and sustainability outcome.
      We used the Normalization Process Theory and the National Health Services
      Sustainability Model, an operational definition for Lean and a comprehensive
      definition for sustainability as guidance for data extraction and analysis. Our
      initial program theory with was refined using a blend of abductive and
      retroductive analytical processes. RESULTS: We identified six published primary
      research studies, two published quality improvement case studies, and three
      unpublished quality improvement case reports. Five CMO hypotheses from our
      initial program theory were substantially supported after synthesis, "sense
      making and value congruency," "staff engagement and empowerment," and the "ripple
      effect" or causal pathway between Lean implementation outcomes that served as
      facilitating or hindering contexts for sustainability. Overall, there was
      variation with the conceptualization and measurement of sustainability.
      CONCLUSIONS: This study is the first to examine Lean sustainability in pediatric
      healthcare using realist methods. Future research should examine whether the
      predictors of implementation are the same or different to sustainability and
      evaluate the underlying mechanisms that influence the sustainability of Lean.
      There is also a need for research to develop and test conceptual models and
      frameworks on sustainability. SYSTEMATIC REVIEW REGISTRATION: PROSPERO
      CRD42015032252 .

PMID- 30205844
TI  - Antibiotic therapy for skin and soft tissue infections: a protocol for a
      systematic review and network meta-analysis.
AB  - BACKGROUND: Skin and soft tissue infections (SSTIs) in hospital and community
      settings impose a substantial socio-economic burden. Therapeutic uncertainty due
      to the availability of a wide range of antibiotics and the need for empirical
      treatment decisions complicate SSTI clinical management. Completion of numerous
      pairwise meta-analyses to account for this variability in antibiotics is
      impractical, and many head-to-head comparisons of potential interest are likely
      not available. In comparing multiple antibiotics simultaneously, this network
      meta-analysis aims to identify the antibiotic(s) with the greatest value in the
      treatment of SSTIs, in terms of patient-important outcomes such as efficacy and
      safety. METHODS: We will conduct a systematic review to identify randomized
      controlled trials of persons with suspected or confirmed SSTI assigned to orally
      or parenterally administered antibiotic therapy that report results on at least
      one outcome of interest. We will search MEDLINE, EMBASE, and the Cochrane Central
      Register of Controlled Trials (CENTRAL), along with trial registries. Our primary
      outcome of interest is clinical success at the test-of-cure visit. Secondary
      outcomes may include (1) early clinical success (2-3 days after the therapy
      starts), (2) mortality, (3) adverse events, (4) treatment duration, and (5)
      length of hospital stay. Independent reviewers will complete screening of titles,
      abstracts, and full texts, data extraction, risk of bias assessment (using the
      Cochrane Risk of Bias tool), and evaluation of the certainty of evidence (using
      the GRADE approach) in duplicate. We will complete pairwise and network meta
      analyses within the Bayesian framework when possible using a random effects
      model. We will stratify SSTIs by severity into uncomplicated and complicated
      SSTIs when possible. Subgroup analyses by age, infection type, comorbidity, and
      suspected or confirmed methicillin-resistant Staphylococcus aureus (MRSA)
      associated infection are planned. DISCUSSION: This study has several strengths
      compared to previous reviews: inclusion of a wider range of infection types,
      antibiotics, and outcomes; a comprehensive search strategy; a priori subgroup
      analyses; application of GRADE; and improved interpretability of findings through
      visual presentation of results. We hope our findings will inform future research,
      health care professionals, and policy makers resulting in improved evidence-based
      clinical management of SSTIs. SYSTEMATIC REVIEW REGISTRATION: PROSPERO
      CRD42018085607.

PMID- 30205845
TI  - A 2-year-old girl with chronic crackles after respiratory syncytial virus
      infection: a case report.
AB  - BACKGROUND: Respiratory syncytial virus is the most common cause of lower
      respiratory tract infections in infants and young children. While the majority of
      infants display only mild upper respiratory tract infection or occasionally
      otitis media, around one-third will develop an infection of the lower respiratory
      tract, usually bronchiolitis. There is now convincing evidence from a number of
      cohorts that respiratory syncytial virus is a significant, independent risk
      factor for later wheezing, at least within the first decade of life. The wide
      variation in response to respiratory syncytial virus infection suggests that
      susceptibility and disease are influenced by multiple host-intrinsic factors.
      CASE PRESENTATION: A 2-year-old white girl presented to our Pediatric Allergy
      Clinic with recurrent crackles in addition to cough, fevers, and labored
      breathing since her first respiratory syncytial virus infection at the age of 7
      months. She had been under the care of pulmonologists, who suspected childhood
      interstitial lung disease. She was hospitalized eight times due to exacerbation
      of symptoms and prescribed systemic and inhaled steroids, short-acting beta2
      mimetics, and antileukotriene. There was no short-term clinical improvement at
      that time between hospitalizations. During her hospital stay at the Pneumonology
      and Cystic Fibrosis Department in Rabka a bronchoscopy with bronchoalveolar
      lavage was performed. Laboratory bacteriological tests found high colony count of
      Moraxella catarrhalis (beta-lactamase positive), sensitive to amoxicillin
      clavulanate, in bronchial secretions and swabs from her nose. After this,
      infections were treated with antibiotics; she remained in good condition without
      symptoms. Crackles and wheezing recurred only during symptoms of infections.
      Therefore, we hypothesize that respiratory syncytial virus infection at an early
      age might cause severe damage of the lung epithelium and prolonged clinical
      symptoms, mainly crackles and wheezing, each time the child has a respiratory
      infection. CONCLUSIONS: This case illustrates the importance of respiratory
      syncytial virus infection in an immunocompetent child. Pediatricians need to have
      a high index of suspicion and knowledge of recurrent symptoms associated with
      severe damage of the lung epithelium to establish the correct diagnosis.

PMID- 30205843
TI  - Conservation of biodiversity in the genomics era.
AB  - "Conservation genomics" encompasses the idea that genome-scale data will improve
      the capacity of resource managers to protect species. Although genetic approaches
      have long been used in conservation research, it has only recently become
      tractable to generate genome-wide data at a scale that is useful for
      conservation. In this Review, we discuss how genome-scale data can inform species
      delineation in the face of admixture, facilitate evolution through the
      identification of adaptive alleles, and enhance evolutionary rescue based on
      genomic patterns of inbreeding. As genomic approaches become more widely adopted
      in conservation, we expect that they will have a positive impact on management
      and policy decisions.

PMID- 30205847
TI  - Body mass but not wing size or symmetry correlates with life span of honey bee
      drones.
AB  - In social insects such as the honey bee, the quality of drones at the time of
      their emergence can affect their maintenance in the colony until maturity. Body
      mass, wing size and wing asymmetry of emerging honey bee drones were measured and
      correlated with their life span in the colony and compared between individuals
      reaching maturity or not. The life span of drones differed among colonies in
      which they were maintained after emergence but not between colonies in which they
      were reared. More drones heavier at emergence reached sexual maturity at 15 days
      and had a longer life span compared with light-weight drones of lower mass. The
      size and symmetry of drone forewings was not correlated with their life span. Our
      results suggest that body mass at emergence is a good predictor of drone survival
      in the colony.

PMID- 30205848
TI  - Informal caregiving patterns and trajectories of psychological distress in the UK
      Household Longitudinal Study.
AB  - BACKGROUND: Approximately seven million people in the UK are engaged in informal
      caregiving. Informal caregivers are at risk of poorer mental and physical health.
      However, less is known about how the relationship between the informal caregiving
      and psychological distress changes over time. The aim of this study was to
      investigate longitudinal associations between the informal caregiving and
      psychological distress amongst UK men and women aged 16+. METHODS: Data were
      analysed from the UK Household Longitudinal Study (UKHLS, n = 9368), a nationally
      representative study of UK households. Longitudinal linear mixed modelling was
      used to estimate associations between the longitudinal patterns of informal
      caregiving (non-caregiver/one episode of 1-2 years/intermittent caregiving/3+
      years caregiving) and trajectories of psychological distress across seven waves
      of UKHLS data. RESULTS: Informal caregiving was not associated with psychological
      distress for men. Women engaged in long-term (?3 years) or intermittent
      caregiving had higher levels of psychological distress at the point of
      initiation, compared with women who were not caregivers throughout the study
      period (3+ years caregiver: regression coefficient 0.48, 95% confidence interval
      (CI) 0.07-0.89; intermittent caregiver: regression coefficient 0.47, 95% CI 0.02
      0.92). Trajectories of psychological distress changed little over time,
      suggesting a plateau effect for these caregiving women. CONCLUSIONS: Women
      engaged in long-term or repeated shorter episodes of informal caregiving reported
      more symptoms of psychological distress than non-caregiving women. Given the
      increased risk of reporting psychological distress and the increasing importance
      of the informal care sector, the risk of poorer mental health of informal
      caregivers should be a priority for public health.

PMID- 30205846
TI  - Understanding variations in catastrophic health expenditure, its underlying
      determinants and impoverishment in Sub-Saharan African countries: a scoping
      review.
AB  - BACKGROUND: To assess the financial burden due to out of pocket (OOP) payments,
      two mutually exclusive approaches have been used: catastrophic health expenditure
      (CHE) and impoverishment. Sub-Saharan African (SSA) countries primarily rely on
      OOP and are thus challenged with providing financial protection to the
      populations. To understand the variations in CHE and impoverishment in SSA, and
      the underlying determinants of CHE, a scoping review of the existing evidence was
      conducted. METHODS: This review is guided by Arksey and O'Malley scoping review
      framework. A search was conducted in several databases including PubMed, EBSCO
      (EconLit, PsychoInfo, CINAHL), Web of Science, Jstor and virtual libraries of the
      World Health Organizations (WHO) and the World Bank. The primary outcome of
      interest was catastrophic health expenditure/impoverishment, while the secondary
      outcome was the associated risk factors. RESULTS: Thirty-four (34) studies that
      met the inclusion criteria were fully assessed. CHE was higher amongst West
      African countries and amongst patients receiving treatment for HIV/ART, TB,
      malaria and chronic illnesses. Risk factors associated with CHE included
      household economic status, type of health provider, socio-demographic
      characteristics of household members, type of illness, social insurance schemes,
      geographical location and household size/composition. The proportion of
      households that are impoverished has increased over time across countries and
      also within the countries. CONCLUSION: This review demonstrated that
      CHE/impoverishment is pervasive in SSA, and the magnitude varies across and
      within countries and over time. Socio-economic factors are seen to drive CHE with
      the poor being the most affected, and they vary across countries. This calls for
      intensifying health policies and financing structures in SSA, to provide
      equitable access to all populations especially the most poor and vulnerable.
      There is a need to innovate and draw lessons from the 'informal' social
      networks/schemes as they are reported to be more effective in cushioning the
      financial burden.

PMID- 30205849
TI  - The importance of accounting for testing and positivity in surveillance by time
      and place: an illustration from HIV surveillance in Japan.
AB  - The number of tests performed is an important surveillance indicator. We
      illustrate this point using HIV surveillance data, focusing on Tokyo and Okinawa,
      two prefectures with high HIV notification rates in Japan. Restricting to data
      reported from local public health centres and affiliate centres where testing
      data are accessible, we assessed HIV surveillance data during 2007-2014, based on
      the annual HIV notification rate (per 100 000 population), HIV testing rate (per
      100 000 population) and proportion testing HIV-positive (positivity). Nationally,
      testing activity and positivity showed an inverse relationship; in 2008, the
      testing rate peaked, but positivity was lowest. While notification rates were
      higher for Tokyo (median = 0.98, range = 0.89-1.33) than Okinawa (median = 0.61,
      range = 0.42-1.09), Okinawa had slightly higher testing rates (median = 187,
      range = 158-274) relative to Tokyo (median = 172, range = 163-210). Positivity
      was substantially lower in Okinawa (median = 0.34%, range = 0.24-0.45%) compared
      with Tokyo (median = 0.57%, range = 0.46-0.67%). Relative to the national testing
      rate (median = 85, range = 80-115) and positivity (median = 0.34%, range = 0.28
      0.36%), Tokyo had higher positivity, despite more testing. In 2014 in Okinawa,
      all three indicators increased, providing a strong reason to be concerned as
      positivity increased despite more testing. Together with other information,
      accounting for testing and positivity improve interpretation of surveillance data
      to guide public health assessments.

PMID- 30205851
TI  - A spatial and temporal analysis of risk factors associated with sporadic Shiga
      toxin-producing Escherichia coli O157 infection in England between 2009 and 2015.
AB  - Infection with STEC O157 is relatively rare but has potentially serious sequelae,
      particularly for children. Large outbreaks have prompted considerable efforts
      designed to reduce transmission primarily from food and direct animal contact.
      Despite these interventions, numbers of infections have remained constant for
      many years and the mechanisms leading to many sporadic infections remain
      unclear.Here, we show that two-thirds of all cases reported in England between
      2009 and 2015 were sporadic. Crude rates of infection differed geographically and
      were highest in rural areas during the summer months. Living in rural areas with
      high densities of cattle, sheep or pigs and those served by private water
      supplies were associated with increased risk. Living in an area of lower
      deprivation contributed to increased risk but this appeared to be associated with
      reported travel abroad. Fresh water coverage and residential proximity to the
      coast were not risk factors.To reduce the overall burden of infection in England,
      interventions designed to reduce the number of sporadic infections with STEC
      should focus on the residents of rural areas with high densities of livestock and
      the effective management of non-municipal water supplies. The role of sheep as a
      reservoir and potential source of infection in humans should not be overlooked.

PMID- 30205850
TI  - Animal-type melanoma: dog or wolf? A review of the literature and a case report.
AB  - The human animal type melanoma (ATM) is a rare subtype of melanoma characterised
      by the proliferation of pigmented dermal epithelioid and spindled melanocytes.
      However, this variant of melanoma is still lacking a precise nosography
      definition and classification for the difficulty to be distinguished from other
      more common melanocytic lesions, as well as for its peculiar biological
      behaviour. On the other hand, the contribution of scientific literature to this
      issue is fragmented and limited to the description of very few cases. Starting
      from the presentation of a case with abnormally aggressive clinical features,
      here we revisit the current knowledge on ATM from its dermatologic patterns,
      epidemiology, demography and histopathology to the clinical management. Peculiar
      accuracy has also been reserved to several histopathologic criteria, which are
      critical for the differential diagnosis from other melanocytic diseases in
      junction with molecular data deriving from recent cytogenetic and mutational
      characterisation of this tumour.

PMID- 30205853
TI  - Potential role of the heat shock protein 90 (hsp90) in buffering mutations to
      favour cyclical parthenogenesis in the peach potato aphid Myzus persicae
      (Aphididae, Hemiptera).
AB  - Heat-shock proteins 90 (hsp90s) are a class of molecules able to stabilize a
      network of 'client' proteins that are involved in several processes. Furthermore,
      recent studies indicated that mutations in the hsp90-encoding gene induce a wide
      range of phenotypic abnormalities, which have been interpreted as an increased
      sensitivity of different developmental pathways to hidden/cryptic mutations. In
      order to verify the role of hsp90 in aphids, we amplified and sequenced the hsp90
      gene in 17 lineages of the peach potato aphid Myzus persicae (Sulzer, 1776)
      looking for the presence of mutations. In particular, we compared lineages with
      different reproductive modes (obligate vs. cyclical parthenogenesis), propensity
      to develop winged females and karyotype stability. Differently from the cyclical
      parthenogenetic lineages that possessed functional hsp90 genes, the seven
      analysed asexual lineages showed severe mutations (including frameshift and non
      sense mutations). In vivo functional assays with the hsp90-inhibitor geldanamycin
      showed that some lineages with cyclical parthenogenesis may lose their ability to
      induce sexuales in the absence of active hsp90 revealing the presence of cryptic
      mutations in their genomes. As a whole, our data suggest that hsp90 could play in
      aphids a role in buffering hidden/cryptic mutations that disrupt cyclical
      parthenogenesis.

PMID- 30205852
TI  - Invasive slug Meghimatium pictum (Stoliczka, 1873) infected by Angiostrongylus
      costaricensis Morera & Cespedes, 1971, and the possible risk of human infection
      associated with grape consumption.
AB  - Many molluscs may be infected with angiostrongylid larvae. Following the
      histopathological diagnosis of abdominal angiostrongyliasis in a grape farmer
      from southern Brazil, molluscs in the area were investigated. During a nocturnal
      search, 245 specimens of slugs were collected and identified as the invasive
      Chinese slug Meghimatium pictum. Angiostrongylus costaricensis worms were
      recovered from mice that were experimentally infected with larvae obtained from
      11 (4.5%) of the molluscs. This study presents the first report of M. pictum
      being identified as an intermediate host for A. costaricensis. Most of the slugs
      were collected from grape plants, which suggests that transmission may be
      associated with grape consumption.

PMID- 30205854
TI  - Role of ecology and phylogeny in determining tapeworm assemblages in skates
      (Rajiformes).
AB  - An understanding of the mechanisms that determine host and parasite relationships
      is a central aim in parasitology. Association of a parasite species with a host
      species may be influenced primarily by phylogenetic constraints that cause
      parasite species to co-speciate with their host species, or predominantly by
      ecological parameters that influence all other co-evolutionary scenarios. This
      study aimed to investigate the role of co-speciation as well as other co
      evolutionary scenarios in influencing the assemblages of tapeworm parasites
      (marine cestodes) in skate hosts (Rajiformes) using a modification of the PACo
      (Procrustean Approach to Cophylogeny) method. The study found that phylogeny and
      host ecology are both significant predictors of skate-tapeworm relationships,
      implying that co-speciation as well as other co-evolutionary scenarios are
      shaping these associations. The study also investigated the key ecological
      parameters influencing host-switching and found that host diet, distribution
      depth, average body size and geographical location have a combined effect. Given
      the importance of parasites in ensuring healthy and stable marine ecosystems, the
      findings of this study have implications for conservation management worldwide.

PMID- 30205855
TI  - Vulnerability to psychosocial disability in psychosis.
AB  - Psychosocial disability affects a number of individuals with psychosis and often
      begins years before the formal onset of disorder. This suggests that for many,
      their psychosocial disability is enduring, and targeted interventions are
      therefore needed earlier in their developmental trajectories to ensure that
      psychosocial disability does not become entrenched. Poor psychosocial functioning
      also affects individuals with a range of different emerging mental health
      problems, putting these young people at risk of long-term social marginalisation
      and economic disadvantage; all of which are known risk factors for the
      development of psychosis. Identification of the markers of poor psychosocial
      functioning will help to inform effective treatments. This editorial will discern
      the early trajectories and markers of poor psychosocial outcome in psychosis, and
      highlight which individuals are most at risk of having a poor outcome. This
      editorial will also discuss whether early interventions are currently being
      targeted appropriately and will propose how intervention and preventative
      strategies can be implemented, to restore psychosocial trajectories in a way that
      enables young people to maximise their life chances.

PMID- 30205857
TI  - Emergency medicine resident wellness: Lessons learned from a national survey.
AB  - CLINICIAN'S CAPSULEWhat is known about the topic?Emergency medicine (EM)
      residents face many wellness challenges during residency.What did this study
      ask?What was the current landscape of Canadian EM resident wellness?What did this
      study find?Canadian EM residents face a multitude of psychosocial and physical
      wellness challenges, while supports may not be adequate.Why does this study
      matter to clinicians?Opportunities exist to further investigate resident wellness
      with validated tools, engage stakeholders, and advance the EM resident wellness
      agenda.

PMID- 30205858
TI  - Back in Print.

PMID- 30205859
TI  - Topical tranexamic acid for the treatment of epistaxis in patients using
      antiplatelet agents.
AB  - : ABSTRACTClinical questionDoes the addition of topical tranexamic acid to
      anterior nasal packing decrease bleeding in patients with epistaxis who are
      taking antiplatelet medications?Article chosenZahed R, Jayazeri M, Naderi A, et
      al. Topical tranexamic acid compared with anterior nasal packing for treatment of
      epistaxis in patients taking antiplatelet drugs: randomized controlled trial.
      Acad Emerg Med 2018;25(3):261-6. OBJECTIVES: The primary outcome of this
      randomized controlled trial was the percentage of patients whose epistaxis had
      stopped at 10 minutes from the time of intervention. Secondary outcomes included
      the frequency of epistaxis recurrence at both 24 hours and 7 days, emergency
      department length of stay, and patient satisfaction.

PMID- 30205860
TI  - #Triage - Formal emergency department triage tools are inefficient, unfair, and
      they waste time and resources.

PMID- 30205861
TI  - A tale of two cities: Divergent management of patients with ureteral colic.

PMID- 30205862
TI  - From abstraction to action: Making wellness practical during residency training.

PMID- 30205863
TI  - Should you adjust your D-dimer?

PMID- 30205856
TI  - Meta-analysis across Cohorts for Heart and Aging Research in Genomic Epidemiology
      (CHARGE) consortium provides evidence for an association of serum vitamin D with
      pulmonary function.
AB  - The role that vitamin D plays in pulmonary function remains uncertain.
      Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D
      (25(OH)D)-pulmonary function association. We conducted the largest cross
      sectional meta-analysis of the 25(OH)D-pulmonary function association to date,
      based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry
      (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic
      Epidemiology Consortium. Data were analysed using linear models by cohort and
      ancestry. Effect modification by smoking status (current/former/never) was
      tested. Results were combined using fixed-effects meta-analysis. Mean serum
      25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1
      nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was
      higher by 1.1 ml in EA (95 % CI 0.9, 1.3; P<0.0001) and 1.8 ml (95 % CI 1.1, 2.5;
      P<0.0001) in AA (P race difference=0.06), and forced vital capacity (FVC) was
      higher by 1.3 ml in EA (95 % CI 1.0, 1.6; P<0.0001) and 1.5 ml (95 % CI 0.8, 2.3;
      P=0.0001) in AA (P race difference=0.56). Among EA, the 25(OH)D-FVC association
      was stronger in smokers: per 1 nmol/l higher 25(OH)D, FVC was higher by 1.7 ml
      (95 % CI 1.1, 2.3) for current smokers and 1.7 ml (95 % CI 1.2, 2.1) for former
      smokers, compared with 0.8 ml (95 % CI 0.4, 1.2) for never smokers. In summary,
      the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In
      EA, a stronger association was observed for smokers compared with never smokers,
      which supports the importance of vitamin D in vulnerable populations.

PMID- 30205864
TI  - A new era in stroke care.

PMID- 30205865
TI  - Determination of Inorganic Arsenic in Seaweed and Seafood by LC-ICP-MS: Method
      Validation.
AB  - Background: Seaweed and seafood often contain both inorganic and organic arsenic
      compounds showing distinct toxicities. Speciation must be taken into account when
      determining the concentrations of arsenic compounds and how they relate to
      overall toxicity. Objective: An analytical method for the quantitation of
      inorganic arsenic was validated in seaweed and seafood. Methods: Food samples
      were heated at 100 degrees C in 0.3 mol/L nitric acid. Arsenic speciation was
      quantitatively determined by LC-inductively coupled plasma-MS (LC-ICP-MS) using
      an octadecilsilane (ODS) column with a mobile phase containing an ion-pair
      reagent. Results: Limits of detection (0.0023-0.012 mg/kg), LOQ (0.0077-0.042
      mg/kg), repeatability (3.0-7.4%), intermediate precision (4.4-7.4%), and trueness
      (recoveries 94-107%) of the proposed method were satisfactory for inorganic
      arsenic in seaweed and seafood. Inorganic arsenic was detected in almost all the
      evaluated dried seaweed products, the Japanese oyster, nam pla, oyster sauce, and
      the intestinal organs of seafood. Conclusions: Among the dried seaweed products,
      significant inorganic arsenic was detected in the brown algae akamoku, hijiki,
      and mozuku. The small amounts of inorganic arsenic detected in nam pla and oyster
      sauce likely derive from the internal organs of the raw seafood used in their
      preparation. Highlights: Arsenic speciation in seaweed and seafood was measured
      by LC-ICP-MS using an ODS column with a mobile phase containing an ion-pair
      reagent. Among the dried seaweed products, brown algae akamoku, hijiki, and
      mozuku contained significantly high levels of inorganic arsenic. The intestinal
      organs of oyster, sardine, and scallop contained higher arsenic levels than the
      muscles.

PMID- 30205866
TI  - Validation of a Modified ANSR(r) for E. coli O157:H7 Method for Detection of E.
      coli O157:H7 in Select Foods.
AB  - Background: The ANSR method is based on isothermal nucleic acid amplification
      technology. The modifications to assay components improve sensitivity of the
      assay and robustness of the internal positive control. Objective: A Performance
      Tested MethodSM validation study was conducted to assess performance of a
      modified version of the ANSR(r) for Escherichia coli O157:H7 method. Methods: The
      validation study included inclusivity/exclusivity, matrix, robustness,
      accelerated stability, and independent laboratory testing. Results: In
      inclusivity testing of 55 strains of E. coli O157:H7 and E. coli O157:NM
      variants, all strains produced positive results. In exclusivity testing of 41
      strains including E. coli of other serotypes and bacteria of closely related
      genera, all strains produced negative results. In matrix testing of beef trim,
      raw ground beef, spinach, and sprout-irrigation water, ANSR method performance
      was compared with that of the U.S. Department of Agriculture Food Safety and
      Inspection Service Microbiology Laboratory Guidebook or the U.S. Food and Drug
      Administration Bacteriological Analytical Manual reference culture procedures.
      Conclusions: all trials, ANSR method performance was not statistically different
      from that of the reference methods. Results of independent laboratory testing of
      ground beef corroborated those of internal testing. Introducing modest changes to
      three assay operating parameters did not materially affect ANSR method
      performance. Finally, accelerated stability testing results of three
      independently manufactured lots of ANSR reagents support a shelf-life of 1 year
      when stored at 2-8 degrees C.

PMID- 30205867
TI  - The Validation of the VereBeefTM Detection Kit Certificate for AOAC Research
      Institute.
AB  - VereBeefTM Detection Kit, incorporating both multiplex PCR and microarray
      technologies on a lab-on-chip platform, is intended for qualitative detection and
      differentiation of Escherichia coli O157:H7, E. coli O26, E. coli O45, E. coli
      O103, E. coli O111, E. coli O121, E. coli O145, Shiga toxin-producing E. coli
      (STEC) virulence factors (stx1A, stx2A, eae), and Salmonella species in one test
      using raw beef trim samples. This product underwent extensive evaluations,
      including inclusivity-exclusivity, method comparison, robustness, lot-to-lot
      variability, and stability studies. The inclusivity/exclusivity study
      demonstrated that VereBeef Detection Kit specifically detects and identifies
      target analytes without occurrence of false-positive and false-negative
      detection. In the method comparison study, the performance of the VereBeef
      Detection Kit was compared with U.S. Department of Agriculture Food Safety and
      Inspection Service Microbiology Laboratory Guidebook's methods for target
      organism detection in raw beef trim using E. coli O157:H7 single inoculation and
      Salmonella and non-O157 STEC dual inoculation. Data demonstrated equivalence in
      both methods. The robustness study showed that changes in the test parameters do
      not impact assay performance. Collectively, VereBeef Detection Kit is able to
      detect target pathogens in raw beef trim with a minimum enrichment time of 8 h
      for E. coli O157:H7 detection and 10 h for Salmonella and non-O157 STEC
      detection.

PMID- 30205868
TI  - Aluminum Foil Lattice Method for Characterizing Performance of Bath-Type
      Ultrasonic-Assisted Extraction Equipment.
AB  - Background: Bath-type ultrasonic-assisted extraction (UAE) has been developed as
      one of the most important sample pretreatment methods, especially for batch
      sample pretreatment. So far, however, requirements for the performance of bath
      type UAE equipment have not been standardized, nor has a suitable evaluation
      method that can be used to judge the feasibility of ultrasonic equipment for
      extraction been presented in the available regulations or standards. Objective: A
      simple and efficient method that can be used to evaluate the performance of bath
      type UAE equipment is necessary to be proposed and established. Methods: First,
      distribution of a sound field in ultrasonic equipment was measured by
      acoustimeter and the dyeing method, through which influencing factors including
      frequency, preheating time, and output power of the equipment, as well as the
      horizontal and vertical position for locating the sample in the equipment, were
      investigated, and optimized parameters for extraction were achieved. Then,
      through the aluminum foil lattice method, by calculating the perforated rate of
      the aluminum foil, cavitation intensity of the ultrasonic equipment can be
      quantitatively determined. Results: With the optimized working conditions and by
      selecting appropriate parameters for the aluminum foil, perforated holes formed
      on the foil displayed a good pattern. Further validation experiments indicated
      conformity between the established method and the actual extraction effect of the
      ultrasonic equipment, proposing a suitable requirement for the cavitation effect
      of the bath-type UAE equipment. Conclusions: The aluminum foil lattice method has
      been proved to be simple, convenient, inexpensive, and reliable for quickly
      evaluating the extraction performance of bath-type UAE equipment.

PMID- 30205869
TI  - ESCAIDE 2018 - call for late breakers.

PMID- 30205871
TI  - Yellow fever cases in French Guiana, evidence of an active circulation in the
      Guiana Shield, 2017 and 2018.
AB  - French Guiana (FG) is a French overseas region bordering Brazil and Suriname that
      is considered endemic for yellow fever (YF); vaccination is compulsory for
      residents and travellers. In August 2017 and 2018, two sporadic YF cases were
      notified 1 year apart, confirming that sylvatic YF virus circulation is active in
      the region. YF vaccination coverage should be closely monitored and improved in
      FG and neighbouring territories and clinicians should be aware of the risk.

PMID- 30205870
TI  - Trends and determinants of antimicrobial susceptibility of Neisseria gonorrhoeae
      in the Netherlands, 2007 to 2015.
AB  - BackgroundNeisseria gonorrhoeae antibiotic resistance surveillance is important
      to maintain adequate treatment. We analysed 2007-15 data from the Gonococcal
      Resistance to Antimicrobials Surveillance (GRAS), which currently includes 19 of
      25 sexually transmitted infection (STI) centres in the Netherlands. Methods: From
      each patient with a gonorrhoea culture, the minimum inhibitory concentration
      (MIC) for several antibiotics was determined. Time trends were assessed by
      geometric means and linear regression of logarithmic MIC. Determinants for
      decreased susceptibility to ceftriaxone (MIC > 0.032 mg/L) and resistance to
      cefotaxime (MIC > 0.125 mg/L) and azithromycin (MIC > 0.5 mg/L) were assessed
      using stratified logistic regression. Results: 11,768 isolates were analysed. No
      ceftriaxone resistance was found. In 2015, 27 of 1,425 isolates (1.9%) were
      resistant to cefotaxime and 176 of 1,623 (10.9%) to azithromycin. Ceftriaxone
      susceptibility showed no trend (p = 0.96) during the study period, but cefotaxime
      MIC decreased (p < 0.0001) and azithromycin MIC increased (p < 0.0001)
      significantly. Concerning ceftriaxone, isolates of men who have sex with men
      (MSM) from 2013 (p = 0.0005) and 2014 (p = 0.0004) were significantly associated
      with decreased susceptibility. Significant determinants for cefotaxime resistance
      were having >= 6 partners for women (p = 0.0006). For azithromycin,isolates from
      MSM collected in 2012 (p = 0.0035), 2013 (p = 0.012), and 2014 (p = 0.013), or
      from non-Dutch (p < 0.0001) or older (>= 35 years; p = 0.01) MSM were
      significantly associated with susceptibility. Resistance in heterosexual men was
      significantly associated with being >= 25 years-old (p = 0.0049) or having 3-5
      partners (p = 0.01). Conclusions: No ceftriaxone resistance was found, but
      azithromycin MIC increased in 2007-15. Resistance determinants could help with
      focused intervention strategies.

PMID- 30205872
TI  - Call for ECDC Fellowship Programme cohort 2019.

PMID- 30205873
TI  - Multicriteria decision analysis (MCDA) for health technology assessment: the
      Queensland Health experience.
AB  - Objectives In determining whether new health technologies should be funded,
      health technology assessment (HTA) committees prefer explicit to implicit methods
      of analysis in enhancing transparency and consistency of decision making. The aim
      of this study was to develop and pilot a multicriteria decision analysis (MCDA)
      framework for the Queensland Department of Health HTA program committee, which
      weighted decision making criteria according to their perceived importance as
      determined by group consensus.Methods The criteria used in the MCDA framework
      were identified by reviewing the five unweighted criteria used in the existing
      process, consultation with committee members and literature review. Criteria were
      clearly defined and ordinal categories of lowest to highest preferred were
      assigned against which technology submissions would be rated. Criteria weights
      were determined through a discrete choice experiment (DCE) survey of committee
      members using validated software. Mean weighted technology scores were then used
      to guide deliberative discussions in determining final funding decisions.Results
      The MCDA framework created one additional criterion to the previous five. The
      criteria and their mean weights identified through the DCE survey were clinical
      benefit and safety (27.2%), quality of evidence (19.2%), implementation capacity
      (16.9%), innovation (15.4%), burden of disease and clinical need (13.3%) and
      societal and ethical values (8.0%). Criterion weights varied considerably between
      individual committee members, with one criterion having a difference of 36.9%
      between the highest and lowest preference weights. Following deliberative
      discussions, all but one of 10 submissions were awarded funding. The submission
      not supported received the third lowest score through the MCDA model.Conclusions
      This pilot application of an MCDA framework, as a complement to committee
      deliberation, conferred greater transparency and objectivity on HTA assessment of
      technologies. The framework converted an implicit, unweighted review process to
      one that is more explicit, flexible in weighting importance and pragmatic.What is
      known about the topic? HTA programs involve complex decision-making processes
      requiring the consideration of multiple criteria. Explicit methods of analysis
      that use weighted criteria according to their relative importance enhance
      transparency and consistency of decision making by HTA committees, and are
      preferred to implicit reviews using unweighted criteria.What does this paper add?
      This article describes the development and piloting of an MCDA framework that
      aims to improve transparency, objectivity and consistency of funding decisions of
      the Queensland HTA committee. Criteria were identified through a review of
      current processes, committee discussions and a literature review, and the Grading
      of Recommendations Assessment, Development and Evaluation (GRADE) quality of
      evidence system. Criteria were weighted using a discrete choice experiment
      involving committee members. Using weighted criteria, mean technology scores were
      calculated and incorporated into deliberative discussions to determine funding
      decisions.What are the implications for practitioners? The MCDA framework
      described here converted a more implicit, unweighted process to one that was more
      pragmatic, explicit and flexible in scoring HTA submissions. This framework may
      be useful to other HTA programs and could be expanded to resource allocation
      decision making in many other healthcare settings.

PMID- 30205874
TI  - Osteoarthritis and atherosclerosis in joint disease".

PMID- 30205875
TI  - Crispr/Cas9 homologous recombination (HR).

PMID- 30205876
TI  - CRISPR/Cas9-mediated genome editing in human stem cell-derived cardiomyocytes:
      Applications for cardiovascular disease modelling and cardiotoxicity screening.
AB  - Cardiovascular diseases (CVDs) are leading causes of death worldwide, and drug
      induced cardiotoxicity is among the most common cause of drug withdrawal from the
      market. Improved models of cardiac tissue are needed to study the mechanisms of
      CVDs and drug-induced cardiotoxicity. Human pluripotent stem cell-derived
      cardiomyocytes (hPSC-CM) have provided a major advance to our ability to study
      these conditions. Combined with efficient genome editing technologies, such as
      CRISPR/Cas9, we now have the ability to study with greater resolution the genetic
      causes and underlying mechanisms of inherited and drug-induced cardiotoxicity,
      and to investigate new treatments. Here, we review recent advances in the use of
      hPSC-CMs and CRISPR/Cas9-mediated genome editing to study cardiotoxicity and
      model CVD.

PMID- 30205879
TI  - CRISPR/Cas9 genome engineering in hematopoietic cells.
AB  - The development of genome editing tools capable of modifying specific genomic
      sequences with unprecedented accuracy has opened up a wide range of new
      possibilities in targeted gene manipulation. In particular, the CRISPR/Cas9
      system, a repurposed prokaryotic adaptive immune system, has been widely adopted
      because of its unmatched simplicity and flexibility. In this review we discuss
      achievements and current limitations of CRISPR/Cas9 genome editing in
      hematopoietic cells with special emphasis on its potential use in ex vivo gene
      therapy of monogenic blood disorders, HIV and cancer.

PMID- 30205877
TI  - CRISPR/Cas9 genome surgery for retinal diseases.
AB  - Retinal diseases that impair vision can impose heavy physical and emotional
      burdens on patients' lives. Currently, clustered regularly interspaced short
      palindromic repeats (CRISPR) is a prevalent gene-editing tool that can be
      harnessed to generate disease model organisms for specific retinal diseases,
      which are useful for elucidating pathophysiology and revealing important links
      between genetic mutations and phenotypic defects. These retinal disease models
      are fundamental for testing various therapies and are indispensible for potential
      future clinical trials. CRISPR-mediated procedures involving CRISPR-associated
      protein 9 (Cas9) may also be used to edit genome sequences and correct mutations.
      Thus, if used for future therapies, CRISPR/Cas9 genome surgery could eliminate
      the need for patients with retinal diseases to undergo repetitive procedures such
      as drug injections. In this review, we will provide an overview of CRISPR/Cas9,
      discuss the different types of Cas9, and compare Cas9 to other endonucleases.
      Furthermore, we will explore the many ways in which researchers are currently
      utilizing this versatile tool, as CRISPR/Cas9 may have far-reaching effects in
      the treatment of retinal diseases.

PMID- 30205878
TI  - Developing precision medicine using scarless genome editing of human pluripotent
      stem cells.
AB  - Many avenues exist for human pluripotent stem cells (hPSCs) to impact medical
      care, but they may have their greatest impact on the development of precision
      medicine. Recent advances in genome editing and stem cell technology have enabled
      construction of clinically-relevant, genotype-specific "disease-in-a-dish"
      models. In this review, we outline the use of genome-edited hPSCs in precision
      disease modeling and drug screening as well as describe methodological advances
      in scarless genome editing. Scarless genome-editing approaches are attractive for
      genotype-specific disease modeling as only the intended DNA base-pair edits are
      incorporated without additional genomic modification. Emerging evidentiary
      standards for development and approval of precision therapies are likely to
      increase application of disease models derived from genome-edited hPSCs.

PMID- 30205880
TI  - CRISPR/Cas9 disease models in zebrafish and Xenopus: The genetic renaissance of
      fish and frogs.
AB  - The speed by which clinical genomics is currently identifying novel potentially
      pathogenic variants is outperforming the speed by which these can be functionally
      (genotype-phenotype) annotated in animal disease models. However, over the past
      few years the emergence of CRISPR/Cas9 as a straight-forward genome editing
      technology has revolutionized disease modeling in vertebrate non-mammalian model
      organisms such as zebrafish, medaka and Xenopus. It is now finally possible, by
      CRISPR/Cas9, to rapidly establish clinically relevant disease models in these
      organisms. Interestingly, these can provide both cost-effective genotype
      phenotype correlations for gene-(variants) and genomic rearrangements obtained
      from clinical practice, as well as be exploited to perform translational research
      to improve prospects of disease afflicted patients. In this review, we show an
      extensive overview of these new CRISPR/Cas9-mediated disease models and provide
      future prospects that will allow increasingly accurate modeling of human disease
      in zebrafish, medaka and Xenopus.

PMID- 30205881
TI  - The multiplexed CRISPR targeting platforms.
AB  - The discovery and engineering of the Clustered Regularly Interspaced Short
      Palindromic Repeats (CRISPR) in the past several years have revolutionized
      biomedical research. The CRISPR technology showed great potential to advance
      detection, prevention, and treatment of human diseases in the near future.
      Compared to previous developed genome editing approaches, such as zinc finger
      nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs),
      the CRISPR-based systems have numerous advantages. One example is that the CRISPR
      systems can be easily adopted to efficiently target multiple genes
      simultaneously. Several strategies and toolboxes have been developed to achieve
      multiplexed targeting using the CRISPR systems. In this short review, we will
      discuss the principle, approach, and application of these strategies.

PMID- 30205882
TI  - Trends Form Follows Function: New Ways to Inform and Inspire.

PMID- 30205884
TI  - Effect of Physical Disability on Mortality in Elderly Patients of >=80 Years of
      Age Undergoing Percutaneous Coronary Intervention.
AB  - Functional decrease has been linked with adverse events in different clinical
      contexts. The predictive role of activity of daily living status as assessed by
      the Barthel index (BI) in elderly patients who underwent percutaneous coronary
      intervention (PCI) has not been investigated, yet. In this study, a total of 616
      patients (>=80 years) who underwent PCI between January 2009 and December 2014
      and with available activity of daily living data on admission were stratified
      according to BI (low BI <85, intermediate BI 85 to 95, high BI 100). The primary
      end point was all-cause mortality at a total follow-up of 442 days (interquartile
      range 47 to 1243). Of the 616 patients, 178 (29%), 128 (21%), and 310 (50%) were
      in the low, the intermediate, and the high BI groups, respectively. All-cause
      mortality was 10%, 13%, and 5% in the low, the intermediate, and the high BI
      groups, respectively (log-rank p <0.001). Belonging to the high BI group was
      associated with a reduced risk of all-cause mortality (hazard ratio 0.35, 95%
      confidence interval 0.18 to 0.69, p = 0.002), and associations remained
      significant after multivariable adjustments (adjusted hazard ratio 0.34, 95%
      confidence interval 0.13 to 0.93, p = 0.04). Functional capacity was identified
      as independent predictor of survival in a large cohort of patients who underwent
      PCI. In conclusion, activities of daily living should be incorporated into the
      risk stratification of elderly patients with coronary artery disease.

PMID- 30205883
TI  - Tongue necrosis secondary to mucormycosis in a diabetic patient: A first case
      report in Malaysia.
AB  - Mucormycosis is a rare fungal infection and high mortality that commonly affects
      patients with the weakened immune system. We present an unusual case of tongue
      necrosis probably due to the healthcare-associated mucormycosis (HCM) in a
      diabetic patient. Although cannot be proved with certainty, we surmise that
      intubation as a risk factor in our case. The diagnosis was confirmed by
      histopathological examination (HPE) of the necrotic tissue specimen. The patient
      was responded well to lipid complex amphotericin B (250mg) regime after surgery.
      Subsequent follow up revealed that no signs of recurrence. Early, recognition,
      diagnosis, prompt treatment and awareness among clinician are representing the
      most effective way of managing the disease.

PMID- 30205885
TI  - Meta-Analysis Comparing Primary Percutaneous Coronary Intervention Versus
      Pharmacoinvasive Therapy in Transfer Patients with ST-Elevation Myocardial
      Infarction.
AB  - ST-elevation myocardial infarction patients presenting at non-percutaneous
      coronary intervention (PCI)-capable hospitals often need to be transferred for
      primary percutaneous coronary intervention (PPCI). This increases time to
      revascularization, leading to increased risk of in-hospital mortality. With
      recent focus on total ischemic time rather than door-to-balloon time as the
      principal determinant of outcomes in ST-elevation myocardial infarction patients,
      pharmacoinvasive therapy (PIT) has gained attention as a possible improvement
      over PPCI in patients requiring transfer. Our objective was to observe how PIT
      stands against PPCI in terms of safety and efficacy. Electronic databases were
      searched for randomized controlled trials and observational studies comparing
      PPCI to PIT. PIT was defined as administration of thrombolytic drugs followed by
      immediate PCI only in case of failed thrombolysis. Results from studies were
      pooled using a random-effects model. We identified 17 relevant studies (6
      randomized controlled trials, 11 observational studies) including 13,037
      patients. Overall, there was no significant difference in short-term mortality
      (odds ratio [OR] = 1.20 [0.97 to 1.49]; I2 = 14.2%; p = 0.099); however, PIT
      significantly decreased short-term mortality (OR = 1.46 [1.08 to 1.96]; I2 = 0%;
      p = 0.01) in those studies with a symptom-onset-to-device time >=200 minutes.
      There was a significantly lower risk reinfarction (OR = 0.69 [0.49 to 0.97]; I2 =
      0%; p = 0.033) in the PPCI group, while the risk of cardiogenic shock was
      significantly higher (OR = 1.48 [1.13 to 1.94]; I2 = 0%; p = 0.005). In
      conclusion, PIT versus PPCI decisions should preferably be customized in patients
      presenting to non-PCI capable hospitals. Factors that need to be considered
      include symptom-onset to first medical contact time, expected time of transfer to
      a PCI-capable hospital, and patients risk factors.

PMID- 30205887
TI  - Meta-Analysis Comparing Dual Versus Single Antiplatelet Therapy in Combination
      With Antithrombotic Therapy in Patients With Atrial Fibrillation Who Underwent
      Percutaneous Coronary Intervention With Stent Implantation.
AB  - The coexistence of atrial fibrillation and coronary artery disease is commonly
      found in clinical practice. The aim of this meta-analysis is to compare the
      clinical efficacy and safety of dual versus single antiplatelet therapy in
      combination with antithrombotic therapy in patients with atrial fibrillation
      undergoing percutaneous coronary intervention. PubMed, EMBASE and Web of Science
      databases were systematically evaluated for articles published up to October 31,
      2017. The risk ratios (RR) were extracted from each study. Pooled estimates with
      corresponding 95% confidence intervals (CI) were estimated by a fixed or random
      effects model. Eight studies involving a total of 10,861 patients with atrial
      fibrillation were included in this meta-analysis. Five thousand sixty-six
      participants received dual antiplatelet therapy together with warfarin or new
      oral anticoagulation (triple antithrombotic therapy, TT) and 5,795 participants
      received single antiplatelet therapy together with warfarin or new oral
      anticoagulation (dual antithrombotic therapy). TT was associated with a
      significantly higher incidence of all (RR 1.45, p <0.001) and major (RR 1.77, p
      <0.001) bleeding events, but no difference with regard to stroke, in-stent
      thrombosis, major adverse cardiovascular events, and all-cause mortality rate. In
      conclusion, as compared to TT, dual antithrombotic therapy is equally effective
      in reducing stroke, in-stent thrombosis, major adverse cardiovascular events, and
      all-cause mortality rate, but shows beneficial effect in reducing overall
      bleeding incidence in atrial fibrillation patients who underwent percutaneous
      coronary intervention.

PMID- 30205886
TI  - Usefulness of Intravenous Sodium Nitrite During Resuscitation for the Treatment
      of Out-of-Hospital Cardiac Arrest.
AB  - It is hypothesized that intravenous (IV) sodium nitrite given during
      resuscitation of out-of-hospital cardiac arrest (OHCA) will improve survival. We
      performed a phase 1 open-label study of IV sodium nitrite given during
      resuscitation of 120 patents with OHCA from ventricular fibrillation or
      nonventricular fibrillation initial rhythms by Seattle Fire Department
      paramedics. A total of 59 patients received 25 mg (low) and 61 patients received
      60 mg (high) of sodium nitrite during resuscitation from OHCA. Treatment effects
      were compared between high- and low-dose nitrite groups, and all patients in a
      concurrent local Emergency Medical Services registry of OHCA. Whole blood nitrite
      levels were measured in 97 patients. The rate of return of spontaneous
      circulation (48% vs 49%), rearrest in the field (15% vs 25%), use of
      norepinephrine (12% vs 12%), first systolic blood pressure (124 +/- 32 vs 125 +/-
      38 mm Hg), survival to discharge (23.7% vs 16.4%), and neurologically favorable
      survival (18.6% vs 11.5%) were not significantly different in the low and high
      nitrite groups. There were no significant differences in these outcomes among
      patients who received IV nitrite compared with concurrent registry controls. We
      estimate that 60 mg achieves whole blood nitrite levels of 22 to 38 MUM 10
      minutes after administration, whereas 25 mg achieves a level of 9 to 16 MUM 10
      minutes after delivery. In conclusion, administration of IV nitrite is feasible
      and appears to be safe in patients with OHCA, permitting subsequent evaluation of
      the effectiveness of IV nitrite for the treatment of OHCA.

PMID- 30205888
TI  - Relation of Obstructive Sleep Apnea to Risk of Hospitalization in Patients With
      Heart Failure and Preserved Ejection Fraction from the National Inpatient Sample.
AB  - Obstructive Sleep Apnea (OSA) increases the risk of diastolic dysfunction and
      heart failure. The impact of OSA on hospitalization for heart failure with
      preserved ejection fraction (HFpEF) is not well elucidated. We used data from the
      National Inpatient Sample for the years 2012 to 2014. We identified discharges
      (age >=18 years) associated with OSA and HFpEF using the International
      Classification of Diseases, Ninth Revision, Clinical Modification codes (327.23
      and 428.3x), respectively. Propensity score analysis, adjusting for age, gender,
      race, and comorbidities, compared the rates of admission for HFpEF in patients
      with OSA to those without OSA. Out of 12,608,637 discharges included, there were
      147,463 patients with HFpEF, and 653,762 or 5.2% of all discharges had OSA. The
      prevalence of OSA in patients with HFpEF was 16.8%. Patients with OSA were older,
      more likely to be men, more likely to have diabetes, hypertension, history of
      coronary artery disease, chronic kidney disease, obesity, atrial fibrillation,
      African-American race, and smoking status. In patients with OSA, HFpEF occurred
      in 3.8% versus 1.0%, with adjusted odds ratio: 2.2 (95% confidence interval 2.16
      to 2.23), p <0.001. Subgroup analysis showed similar results in men and women.
      After propensity score matching, OSA was associated with increased risk of
      admission with HFpEF, relative risk = 2.2 (95% confidence interval 2.12 to 2.21).
      In conclusion, OSA was associated with increased risk of hospitalization for
      HFpEF.

PMID- 30205890
TI  - Development of and Progression of Overt Heart Failure in Nonobstructive
      Hypertrophic Cardiomyopathy.
AB  - Only few studies aimed at identifying predictors of heart failure (HF) in
      hypertrophic cardiomyopathy (HC) patients. Furthermore, serial echocardiographic
      analyses are lacking in these patients and little is known about the natural
      progression of left ventricular (LV) abnormalities and their association with HF
      development. Aim of this study was to assess the prognostic value of LV global
      longitudinal strain (GLS) and other clinical and echocardiographic
      characteristics for the development of HF in patients with nonobstructive HC;
      furthermore, changes in echocardiographic parameters over time were correlated
      with HF development. Echocardiography was performed in 236 HC patients (68% men,
      age: 50 +/- 14 years) at their initial visit and during follow-up (6.5(4.1 to
      9.8) years). The end point of new HF development or progression to New York Heart
      Association class III/IV was noted and echocardiographic changes over time were
      compared among patients with and without HF using linear mixed model analysis. In
      total, 40 patients reached the HF end point. Multivariable cox regression
      analysis showed that age (HR 1.04(1.01 to 1.06), p = 0.016), New York Heart
      Association class (HR 2.30(1.07 to 4.95), p = 0.033), GLS (HR 1.15(1.05 to 1.22),
      p = 0.001), and left atrial volume (LAVI, HR 2.22(1.10 to 4.50), p = 0.027) were
      independently associated with the HF end point. Echocardiographic parameters,
      including GLS and LAVI, remained stable over time in patients without HF end
      point, but changed significantly in patients who developed HF (group-time
      interaction, p = 0.042 for GLS and p = 0.027 for LAVI). In conclusion, LV
      dysfunction is a progressive phenomenon in nonobstructive HC patients which can
      be detected by repeated echocardiography. Importantly, GLS and LAVI at baseline
      as well as their changes over time are associated with HF.

PMID- 30205889
TI  - Single Versus Dual Lead Atrioventricular Sequential Pacing for Acquired
      Atrioventricular Block During Transcatheter Aortic Valve Implantation Procedures.
AB  - Atrioventricular block (AVB) after transcatheter aortic valve implantation (TAVI)
      is common. Pacing platforms that preserve atrioventricular (AV) synchrony may be
      beneficial in these patients. Single lead AV sequential pacemakers (VDD) allow AV
      synchrony and, by virtue of implanting a single lead, can be advantageous when
      compared with traditional dual lead (DDD) pacemakers. The objective of this
      retrospective case-controlled study was to compare the strategy of AV sequential
      pacing with a VDD versus DDD pacemaker in consecutive TAVI patients (n = 120)
      with acquired AVB. Patients were classified as receiving a VDD (n = 73) or DDD (n
      = 47) pacemaker. Procedure characteristics, complications, and the need for long
      term ventricular pacing reported. Pacemaker implantation time (51 vs 66 minutes
      and p <0.001), fluoroscopy time (3.7 vs 7.8 minutes and p = 0.004), and radiation
      exposure (dose area product: 6.5 vs 15.3 mGy/cm2 and p = 0.006) were lower in
      patients receiving VDD pacemakers. Procedural complications were similar in the 2
      groups. Overall, 59% of the cohort required >=50% ventricular pacing at 1-year
      follow-up. In conclusion, VDD pacemaker implantation was associated with shorter
      procedure times, lower radiation exposure, and similar safety outcomes when
      compared with DDD pacemaker implantation in TAVI patients with acquired AVB.

PMID- 30205891
TI  - Ventricular Septal Defect in a 66-Year-Old Man.
AB  - A 66-year-old man presented with a moderate-sized ventricular septal defect and
      severe pulmonary hypertension that was responsive to vasodilator therapy. His
      electrocardiogram demonstrated biatrial enlargement and biventricular
      hypertrophy. Presentation at this age is unusual for this type of shunt.

PMID- 30205892
TI  - The role of the polymer matrix in solvent-free hot melt extrusion continuous
      process for mechanochemical synthesis of pharmaceutical cocrystal.
AB  - Solid-state synthesis of pharmaceutical cocrystals is of contemporary interest as
      it offers an efficient way to modify the physicochemical properties of Active
      Pharmaceutical Ingredient (API) including its melting point, solubility,
      compressibility or physical stability, without compromising its structural
      integrity and bioactivity. Therefore, research of novel and emerging techniques
      for solvent-free, continuous and scalable methods for cocrystal formation is of
      paramount importance for further industrial development. In this work we form a
      basis for knowledge-based synthesis and formulation of model pharmaceutical
      cocrystal (flufenamic acid, FFA: nicotinamide, NA; 1:1) via matrix-assisted
      cocrystallisation (MAC) using Hot Melt Extrusion (HME). Five different polymers
      frequently used in pharmaceutical drug delivery: Poloxamer P407 (PXM), PEG-PVA
      copolymer, Soluplus(r) (SOL), PVPVA64 and HPMCAS with different structural
      features and physicochemical properties were investigated as functional matrices
      for FFA:NA cocrystal synthesis via HME. Significant decrease of the torque value
      during MAC process was observed for all investigated polymers as compared to
      extrusion of neat FFA:NA cocrystal. The FFA:NA cocrystal encapsulated in the
      polymer matrix was successfully formed using semicrystalline PXM and PEG-PVA
      polymers at all investigated FFA:NA/polymer ratios. The use of amorphous polymers
      (SOL, PVPVA64, HPMCAS) as a cocrystallisation matrix resulted in formation of
      FFA:NA cocrystal embedded in an amorphous FFA:NA/polymer matrix (at polymer
      contents of 10 and 20 wt.%) or FFA:NA/polymer amorphous composites at SOL and
      PVPVA64 content of 30 wt.%. Furthermore, the significant increase of FFA
      dissolution was observed for FFA:NA cocrystal encapsulated in PXM and PEG-PVA
      matrices as compared to neat FFA form I. FFA form III and FFA:NA cocrystal. The
      presented work enables for the first time knowledge-based approach for
      simultaneous synthesis and formulation of pharmaceutical cocrystals via Hot Melt
      Extrusion a solvent-free, scalable and continuous process.

PMID- 30205893
TI  - Is 11C-choline Positron Emission Tomography/Computed Tomography Accurate to
      Detect Nodal Relapses of Prostate Cancer After Biochemical Recurrence? A
      Multicentric Study Based on Pathologic Confirmation from Salvage Lymphadenectomy.
AB  - BACKGROUND: A 11C-choline positron emission tomography/computed tomography
      (PET/CT) scan is used for restaging prostate cancer (PCa) patients with
      biochemical recurrence (BCR). Only a few reports have focused on the correlation
      between PET/CT and nodal relapse location at pathologic examination. OBJECTIVE:
      To assess the accuracy of PET/CT in predicting the site of nodal relapses in
      patients undergoing pelvic and/or retroperitoneal salvage lymph node dissection
      (sLND). DESIGN, SETTING, AND PARTICIPANTS: Multicentric retrospective study
      including 106 patients with BCR of PCa after radical treatment; all patients but
      six had a PET/CT showing at least one nodal recurrence and received sLND. OUTCOME
      MEASUREMENTS AND STATISTICAL ANALYSIS: PET/CT results were compared with
      histologic findings and analyzed in terms of sensitivity, specificity, and
      accuracy. Multivariable regression analyses were performed. RESULTS AND
      LIMITATIONS: Overall sensitivity, specificity, negative and positive predictive
      value, and accuracy of PET/CT for disease location were 61.6%, 79.3%, 66.3%,
      75.7%, and 70.2%, respectively. Sensitivity was 75.5% in the lower pelvis with
      69.8% specificity. The retroperitoneal region had high specificity (94.7%) but a
      relatively low sensitivity (58.3%). The sLNDs did not find any positive nodes in
      16 patients (15%). According to regression analyses, discriminative accuracy of
      PET/CT was 70.4% and improved with an increased number of dissected nodes and
      prostate-specific antigen doubling time <12 mo. Limitations include retrospective
      design and lack of a standardized sLND template followed for all patients.
      CONCLUSIONS: The ability of PET/CT to detect nodal relapses is limited by a high
      false-positive rate, particularly in the iliac-obturator region and, more
      alarmingly, a high false-negative rate in the common iliac, sacral, and
      retroperitoneal regions. An extended template including pelvic and
      retroperitoneal regions should be adopted when sLND is planned for curative
      intent. PATIENT SUMMARY: The 11C-choline positron emission tomography/computed
      tomography scan is a commonly used tool to restage prostate cancer patients with
      biochemical recurrence, showing an overall per patient accuracy >80%; however,
      its ability to detect the site of nodal relapses remains suboptimal.

PMID- 30205895
TI  - A concurrent examination of protective factors associated with resilience and
      posttraumatic growth following childhood victimization.
AB  - The present study concurrently examined protective factors associated with the
      adaptive outcomes of resilience and posttraumatic growth (PTG; defined as
      positive psychological change resulting from a life crisis or trauma), after
      accounting for relevant demographic factors and the impact of circumstances
      surrounding childhood victimization (i.e., age of first trauma, frequency of
      victimization, and perception of trauma severity). The protective factors
      examined in the present study included social support from friends and family,
      optimism, positive religious coping (i.e., looking to God for support and
      guidance; forgiveness), and negative religious coping (i.e., feeling abandoned by
      God; anger towards God). Participants included 161 college students from the US
      MidSouth, aged 18-24 (Mage = 19.97, SD = 1.86). All participants reported
      experiencing physical violence and/or sexual abuse during their childhood.
      Hierarchical multiple regression analyses indicated that after accounting for
      demographics and circumstances surrounding the childhood victimization, higher
      resilience was associated with greater family support, optimism, and positive
      religious coping, while higher posttraumatic growth was associated with greater
      optimism and positive religious coping. These findings underscore the protective
      role of optimism with respect to both resilience and posttraumatic growth.
      Additionally, results highlight the importance of examining cognitions related to
      religious coping rather than simply assessing broadband religiosity, as only
      positive religious coping was associated with adaptive outcomes. Findings suggest
      the importance of early intervention to bolster protective factors (i.e., family
      support, positive thinking, gratitude, and positive religious coping skills)
      among youth exposed to childhood physical and sexual victimization.

PMID- 30205896
TI  - Reply.

PMID- 30205897
TI  - World Health Organization: Leading surgical care toward sustainable development
      in the era of globalization.

PMID- 30205898
TI  - Folliculotropic Mycosis Fungoides With CD30+ Large-Cell Transformation.

PMID- 30205900
TI  - A scoping review exploring the opioid prescribing practices of US dental
      professionals.
AB  - BACKGROUND: The prescribing practices of dental professionals may play an
      important role in the opioid epidemic. The authors performed a scoping review of
      the current original research literature on dental professionals' prescribing
      practices for opioid analgesics published from 2000 through 2017. TYPES OF
      STUDIES REVIEWED: With the use of a modified Preferred Reporting Items for
      Systematic Reviews and Meta-Analyses approach, the inclusion criteria entailed
      published articles written in English that had an opioid focus, had a dental
      health care professional prescriber, entailed a US setting, were peer reviewed,
      had an identified data source, were not review articles, and were not opinion
      articles. Five databases were searched to identify relevant literature. RESULTS:
      Of 221 articles, 18 met the inclusion criteria. Eight distinct and mutually
      exclusive themes emerged from these studies: impact of patient demographic
      characteristics on opioid prescribing, comparison of opioid prescribing by
      different provider type, quantity of opioids prescribed and consumed, types of
      opioids prescribed by dental professionals, assessment of self-reported opioid
      prescribing, opioid prescriptions by procedure, impact of pharmacy integration
      into dental practice, and implementation of risk mitigation strategies.
      CONCLUSIONS AND PRACTICAL IMPLICATIONS: There is a surprising paucity of research
      that investigated the prescribing patterns of dentists. Available research
      suggests that dental practice does not always align with proposed guidelines for
      opioid prescribing. Some studies that explored interventions found changes in
      prescribing, suggesting the potential benefit of developing practical strategies
      targeted to dental providers who prescribed opioids.

PMID- 30205901
TI  - The pathway from cognitive impairment to caries in older adults: A conceptual
      model.
AB  - BACKGROUND: Caries significantly increases in people with cognitive impairment
      (PWCI). However, the interrelationships among cognitive impairment, dentally
      related function (DRF), oral hygiene, and caries remain unclear, increasing
      difficulties to care appropriately for PWCI. In this study, the researchers
      tested a conceptual model in which impaired DRF acts as a mediator between
      cognitive impairment and poor oral hygiene, which then leads to caries. METHODS:
      The researchers recruited 68 older adult dentate participants with normal to
      severely impaired cognition from 3 assisted-living communities in North Carolina.
      Within 1 week of a calibrated oral examination performed by a geriatric dentist,
      a trained examiner blinded to the oral examination results conducted cognitive
      and functional assessments. The researchers conducted statistical analyses to
      examine the mediating effect of DRF on the relationship between cognitive
      impairment and oral hygiene or caries. RESULTS: Cognitive impairment (beta =
      0.05; standard error [SE], 0.02; P = .017) and DRF (beta = -0.07; SE, 0.02; P =
      .005) were significantly associated with oral hygiene. However, the association
      between cognitive impairment and oral hygiene was greatly reduced and became
      nonsignificant after controlling for DRF (beta = 0.01; SE, 0.03; P = .430),
      suggesting that the effect of cognitive impairment on oral hygiene was mediated
      by DRF. DRF accounted for 80% of the total effect of cognitive impairment on oral
      hygiene. The ratio of the indirect effect to the total effect was .8.
      Associations between either cognitive impairment or DRF and caries were not
      significant, but oral hygiene was significantly associated with caries (beta =
      0.87; SE, 0.28; P < .001). CONCLUSIONS: DRF mediated the association between
      cognitive impairment and oral hygiene. It accounted for 80% of the total impact
      of cognitive impairment on oral hygiene, which was associated with increased
      caries in PWCI. PRACTICAL IMPLICATIONS: As a result of cognitive impairment,
      impaired DRF plays a critical role in the pathway from cognitive impairment to
      oral health decline. Therefore, DRF assessment should be a standard component of
      geriatric dental assessment. A functionally-tailored oral hygiene intervention is
      essential to improve oral health for persons with cognitive impairment.

PMID- 30205899
TI  - Molecular Dynamics Simulations of Kir2.2 Interactions with an Ensemble of
      Cholesterol Molecules.
AB  - Cholesterol is a major regulator of multiple types of ion channels, but the
      specific mechanisms and the dynamics of its interactions with the channels are
      not well understood. Kir2 channels were shown to be sensitive to cholesterol
      through direct interactions with "cholesterol-sensitive" regions on the channel
      protein. In this work, we used Martini coarse-grained simulations to analyze the
      long (MUs) timescale dynamics of cholesterol with Kir2.2 channels embedded into a
      model membrane containing POPC phospholipid with 30 mol% cholesterol. This
      approach allows us to simulate the dynamic, unbiased migration of cholesterol
      molecules from the lipid membrane environment to the protein surface of Kir2.2
      and explore the favorability of cholesterol interactions at both surface sites
      and recessed pockets of the channel. We found that the cholesterol environment
      surrounding Kir channels forms a complex milieu of different short- and long-term
      interactions, with multiple cholesterol molecules concurrently interacting with
      the channel. Furthermore, utilizing principles from network theory, we identified
      four discrete cholesterol-binding sites within the previously identified
      cholesterol-sensitive region that exist depending on the conformational state of
      the channel-open or closed. We also discovered that a twofold decrease in the
      cholesterol level of the membrane, which we found earlier to increase Kir2
      activity, results in a site-specific decrease of cholesterol occupancy at these
      sites in both the open and closed states: cholesterol molecules at the deepest of
      these discrete sites shows no change in occupancy at different cholesterol
      levels, whereas the remaining sites showed a marked decrease in occupancy.

PMID- 30205902
TI  - Induction of Light Tolerance Using Narrowband UV-B in Solar Urticaria.
AB  - INTRODUCTION: Solar urticaria is an uncommon photodermatosis. First-line
      treatment is with antihistamines; second-line treatment includes induction of
      light tolerance using UV phototherapy. OBJECTIVES: We aimed to describe and
      evaluate the effectiveness of a desensitization protocol with narrowband UV-B in
      patients with solar urticaria. MATERIAL AND METHODS: We performed a retrospective
      study of patients with solar urticaria with an action spectrum in the UV-A range,
      the visible light range, or both who had received therapy with narrowband UV-B
      for induction of light tolerance. Short courses of treatment were administered
      (<20 sessions, 3 per week) during spring. The initial dose was determined
      according to the skin type. The Skindex-29 was administered before treatment and
      after summer; a nonvalidated questionnaire was also administered after summer to
      evaluate disease activity and satisfaction with treatment. RESULTS: We included 8
      patients with an action spectrum (4 with visible light and 4 with UVA plus
      visible light). Seventeen courses (1-6 per patient) were administered per year.
      The number of sessions per year ranged from 11 to 20. The mean dose of narrowband
      UV-B per course was 7.45J/cm2. No patients experienced flares or adverse effects
      during treatment. The response was satisfactory in 6 patients. The improvement in
      the overall Skindex-29 score was greater than 20% in 78.6% of cases. The
      improvement in the function and symptoms subscales was over 20% in 71% and 64% of
      cases, respectively. CONCLUSION: Induction of light tolerance with narrowband UV
      B in solar urticaria is safe and effective in a high percentage of patients.

PMID- 30205903
TI  - Corrigendum to Achieving advance care planning in diverse, underserved
      populations Nursing Outlook 66 (2018), 311-315.

PMID- 30205904
TI  - Ethical Principles and Guidelines of Global Health Nursing Practice.
AB  - BACKGROUND: Nurses are among the many U.S. health professionals engaged in
      international learning or service experiences and often travel to low-resource
      countries lacking guidance for ethical practice, respect for host partners, or
      collaborative work in different health systems. PURPOSE: The aim of this study is
      to develop evidence-based principles or guidelines for ethical global health
      nursing practice. METHODS: A three-round Delphi study was conducted. Global
      health nurse experts participated in Round 1 focus group, followed by nurses with
      global health expertise ranking global health nursing statements in Rounds 2 and
      3. DISCUSSION: Findings led to 10 Ethical Principles for Global Health Nursing
      Practice and 30 statements for Ethical Guidelines in Global Health Nursing. These
      Ten principles address beneficence, nonmaleficence, dignity, respect, autonomy,
      social justice, and professional practice. The 30 guidelines offer more specific
      actions nurses must consider when working in global settings.

PMID- 30205905
TI  - Comments on "Novel molecularly imprinted polymer based on beta
      cyclodextrin@graphene oxide: Synthesis and application for selective
      diphenylamine determination".
AB  - This comment mainly deals with a mistake of applying pseudo-first-order kinetic
      model for testing the kinetic behaviors of adsorption.

PMID- 30205906
TI  - [Remifentanil-ketamine vs. propofol-ketamine for sedation in pediatric patients
      undergoing colonoscopy: A randomized clinical trial].
AB  - BACKGROUND AND OBJECTIVES: Pediatric patients frequently require deep sedation or
      general anesthesia for colonoscopy. This study was designed to compare the
      sedative efficacy of remifentanil-ketamine combination with propofol-ketamine
      combination in children undergoing colonoscopy. METHODS: Seventy patients,
      between 2 and 16 years of age, scheduled for diagnostic colonoscopy were randomly
      allocated into two groups. Remifentanil-ketamine group received intravenous
      ketamine 2mg.kg-1 and remifentanil 0.25MUg.kg-1 combination, followed by
      0.1MUg.kg-1.min-1 remifentanil infusion. Propofol-ketamine group received
      intravenous propofol 1 and 2mg.kg-1 ketamine combination, followed by 1mg.kg-1.h
      1 propofol infusion. In the case of children discomfort (cry, movement, and
      cough), remifentanil 0.1MUg.kg-1 in the remifentanil-ketamine group or propofol
      0.5mg.kg-1 in the propofol-ketamine group were administered to improve children
      discomfort. Despite the therapy given above, if children still experience
      discomfort, 1mg.kg-1 of ketamine was administered as a rescue drug, regardless of
      the group. Ramsay sedation score, hemodynamic variables, drug requirements,
      gastroenterologists' satisfaction, colonoscopy duration, recovery time, and side
      effects were recorded throughout the procedure and the recovery period. RESULTS:
      The percentage of patients with a Ramsay sedation score of 4 or higher during the
      procedure was 73.5 and 37.1% in remifentanil-ketamine and propofol-ketamine
      groups, respectively (p=0.02). Systolic and diastolic blood pressure variables
      were significantly higher only after induction in the remifentanil-ketamine group
      than in the propofol-ketamine group (p=0.015). CONCLUSION: Coadministration of
      ketamine with either remifentanil or propofol effectively and safely provides
      sedation and analgesia in children undergoing colonoscopy. Sedation scores were
      significantly better in remifentanil-ketamine group than in propofol-ketamine
      group.

PMID- 30205907
TI  - Predictors of Clostridium difficile infection and predictive impact of probiotic
      use in a diverse hospital-wide cohort.
AB  - BACKGROUND: Hospital-based predictive models for Clostridium difficile infection
      (CDI) may aid with surveillance efforts. METHODS: A retrospective cohort of adult
      hospitalized patients who were tested for CDI between May 1, 2011, and August 31,
      2016, was formed. Proposed clinical and sociodemographic predictors of CDI were
      evaluated using multivariable predictive logistic regression modeling. RESULTS:
      In a cohort of 5,209 patients, including 1,092 CDI cases, emergency department
      location (adjusted odds ratio [aOR], 1.91; 95% confidence interval [CI], 1.51,
      2.41; compared with an intensive care unit reference category, which had the
      lowest observed odds in the study) and prior exposure to a statin (aOR, 1.26, 95%
      CI, 1.06, 1.51), probiotic (aOR, 1.39; 95% CI, 1.08, 1.80), or high-risk
      antibiotic (aOR, 1.54; 95% CI, 1.29, 1.84), such as a cephalosporin, a quinolone,
      or clindamycin, were independent predictors of CDI. Probiotic use did not appear
      to attenuate the odds of CDI in patients exposed to high-risk antibiotics, but
      moderate-risk antibiotics appeared to significantly attenuate the odds of CDI in
      patients who received probiotics. CONCLUSIONS: Emergency department location,
      high-risk antibiotics, probiotics, and statins were independently predictive of
      CDI. Further exploration of the relationship between probiotics and CDI,
      especially in diverse patient populations, is warranted.

PMID- 30205908
TI  - Family functioning moderates the impact of psychosis-risk symptoms on social and
      role functioning.
AB  - BACKGROUND: Youth at clinical high-risk (CHR) for psychosis often experience
      difficulties in social and role functioning. Given evidence that family stress
      and support can impact psychosis-risk symptoms, as well as an individual's
      ability to fulfill social and role functions, family dynamics are hypothesized to
      moderate the effect of psychosis-risk symptoms on functioning. METHODS:
      Participants at CHR (N = 52) completed the clinician-administered Structured
      Interview for Psychosis-risk Syndromes (SIPS) and the Family Assessment Device
      (FAD) General Functioning Scale, a self-report measure of family functioning
      including cohesion and support. Interviewers rated participants' current social
      and role functioning using the Global Functioning: Social and Role Scales.
      RESULTS: Regression results indicated that positive symptoms, but not ratings of
      family functioning, statistically predicted social and role functioning.
      Perceived family functioning, however, moderated the effect of symptoms on
      social/role functioning. For individuals who perceived lower levels of family
      functioning, symptoms were moderately associated with social and role functioning
      (f2 = 0.17 and f2 = 0.23, respectively). In contrast, psychosis-risk symptoms
      were not significantly associated with social/role functioning for individuals
      with higher levels of perceived family functioning. Notably, positive symptoms
      and perceived family functioning were not associated with one another, suggesting
      that perceived family functioning did not directly impact symptom severity, or
      vice versa. CONCLUSIONS: Findings support the notion that family functioning may
      be a clinically meaningful factor for individuals at CHR. Although this cross
      sectional data limits our discussion of potential mechanisms underlying the
      pattern of findings, results suggest that familial support may be beneficial for
      individuals at risk for psychosis.

PMID- 30205910
TI  - Ventricular-Vascular Coupling at Rest and after Exercise Is Associated with Heart
      Failure Hospitalizations in Patients With Coronary Artery Disease.
AB  - BACKGROUND: The ventricular-vascular coupling ratio, defined as the ratio of
      arterial elastance (Ea) to left ventricular end-systolic elastance (Ees), has not
      been examined in populations with coronary artery disease (CAD), and its
      association with heart failure (HF) in this population is unknown. METHODS:
      Ventricular-vascular coupling was measured at rest and after exercise using
      echocardiography and cuff blood pressure in 815 patients with stable CAD enrolled
      in the Heart and Soul Study. Adjusted Cox proportional-hazard models were used to
      evaluate the association between ventricular-vascular coupling and future HF
      hospitalizations. RESULTS: After a median of 8.9 years, 144 patients (18%) were
      hospitalized for HF. After multivariate adjustment, patients in the highest
      tertile of Ees (rest: hazard ratio [HR], 0.31 [95% CI, 0.17-0.57; P < .001];
      exercise: HR, 0.26 [95% CI, 0.13-0.50; P < .001]) were at decreased risk for HF
      hospitalization, while patients in the highest tertile of the Ea/Ees ratio (rest:
      HR, 3.36 [95% CI, 1.91-5.93; P < .001]; exercise: HR, 4.09; [95% CI, 2.22-7.51; P
      < .001]) were at increased risk, compared with the lowest tertiles. Ea and the
      relative change observed in Ees and the Ea/Ees ratio with exercise were not
      associated with HF hospitalizations. CONCLUSIONS: The Ea/Ees ratio and Ees, at
      rest and after exercise, are strongly associated with future HF hospitalizations
      in patients with stable CAD and low rates of baseline HF. Ventricular-vascular
      coupling obtained from echocardiography shows promise as a risk assessment tool
      for HF in patients with CAD.

PMID- 30205909
TI  - Load Dependency of Left Atrial Strain in Normal Subjects.
AB  - BACKGROUND: Left atrial (LA) longitudinal strain is a novel parameter used for
      the evaluation of LA function, with demonstrated prognostic value in several
      cardiac diseases. However, the extent of load dependency of LA strain is not well
      known. The aim of this study was to evaluate the impact of acute changes in
      preload on LA strain, side by side with LA volume, in normal subjects. METHODS:
      Twenty-five healthy volunteers (13 men; mean age, 31 +/- 2 years) were
      prospectively enrolled, who underwent two-dimensional and three-dimensional
      echocardiographic imaging during acute stepwise reductions in preload using a
      tilt maneuver: baseline at 0 degrees , followed by 40 degrees  and 80 degrees .
      Left ventricular and LA size and function parameters were measured using standard
      methodology, and LA strain-time curves were obtained using speckle-tracking
      software (TomTec), resulting in reservoir, conduit, and contractile strain
      components. All parameters were compared among the three loading conditions using
      one-way analysis of variance for repeated measurements. RESULTS: Although there
      were no significant changes in blood pressure, heart rate increased significantly
      with tilt. As expected, LA volumes, left ventricular volumes, and left
      ventricular ejection fraction, as well as E wave, A wave, and e' significantly
      decreased with progressive inclination. In parallel, LA reservoir, conduit, and
      contractile strain values decreased with reduction in preload (reservoir: 42.9 +/
      3.9% to 27.5 +/- 3.8%, P < .001; conduit: 29.3 +/- 2.7% to 20.2 +/- 5.0%, P <
      .001; contractile: 13.6 +/- 2.9% to 7.3 +/- 3.5%, P < .001). Paired post hoc
      analysis showed that all LA strain values were significantly different among all
      three tilt phases. Of note, percentage change in LA reservoir strain was
      significantly smaller than that in LA maximum volume. CONCLUSIONS: In normal
      subjects, LA strain is preload dependent but to a lesser degree than LA volume.
      This difference underscores the relative advantage of LA strain over maximum
      volume, when LA assessment is used as part of the diagnostic paradigm.

PMID- 30205911
TI  - Management of osteoradionecrosis of the jaws with pentoxifylline-tocopherol: a
      systematic review of the literature and meta-analysis.
AB  - Osteoradionecrosis (ORN) of the jaws remains among the most commonly encountered
      and challenging complications of radiotherapy to the head and neck. The purpose
      of this study was to provide a review of the medical management for ORN and
      evaluate the reported outcomes with the use of pentoxifylline and tocopherol
      (PENTO), by means of a systematic review and meta-analysis. The predictor
      variable was the use of PENTO in the treatment of ORN. The outcome variable was
      the proportion of full recovery or significant improvement not requiring further
      intervention. The likelihood function was used to combine the studies and
      estimate the proportion and standard deviation of each outcome by the maximum
      likelihood estimation. Seven studies met the inclusion criteria. A total 211
      patients were treated. One hundred twenty-six patients recovered fully or
      improved significantly not requiring further intervention. Sixty patients
      remained the same, 10 were lost to follow-up, and the disease progressed in 15.
      The current literature supports the use of PENTO in the treatment of ORN of the
      jaws. Additional well-designed prospective studies are needed in order to further
      validate the regimen that can then be employed in the treatment of ORN.

PMID- 30205912
TI  - Relationship of age to foramen of Huschke and investigation of the development of
      spontaneous temporomandibular joint herniation.
AB  - The aim of this study was to determine the prevalence, localization, and width of
      the foramen of Huschke (FH) and the relationship between age and FH. Another aim
      was to investigate the development of spontaneous temporomandibular joint (TMJ)
      herniation. This was a retrospective review of high-resolution computed
      tomography images of the temporal bone of 1025 patients. The prevalence of FH and
      the axial and sagittal diameters of the foramen were evaluated. Cases were found
      in which the TMJ had herniated through FH into the EAC. FH was detected in 137
      (13.4%) of 1025 patients. The prevalence of FH was higher in females (18.4%) than
      in males (6.6%) (P<0.001). The presence of FH increased with age (P=0.005).
      Herniation of the TMJ through FH into the EAC was seen in four patients (0.4%),
      and 2.9% of patients with FH detected had TMJ herniation into the EAC. As well as
      being congenital, FH can also be senile; the prevalence may increase with age.
      Herniation of the TMJ through FH into the EAC is very rare; this was observed in
      0.4% of all patients and 2.9% of patients with FH detected.

PMID- 30205913
TI  - Ovarian hemangioma with Meigs' syndrome.

PMID- 30205914
TI  - [Participation of the immigrant population in breast cancer screening in
      Tarragona, Spain].
AB  - OBJECTIVE: To evaluate the differences between autochthonous and allochthonous
      women's participation in a breast cancer screening programme. METHOD:
      Retrospective study based on data from the Breast Cancer Screening Programme of
      the province of Tarragona (2008-2015). The sample is the target population of the
      programme with known country of origin. RESULTS: Cohort of 40,824 women.
      Allochthonous women participate less than autochthonous women (41.8% vs. 72.3%)
      although they have a similar global detection rate to the latter but with
      differences according to the human development index of their country of origin.
      Both groups present similar tumour stages on detection (p=.59). CONCLUSIONS:
      Strategies specifically aimed at the immigrant population are required to improve
      their participation in breast cancer screening.

PMID- 30205915
TI  - Endoscopic laryngo-pharyngeal surgery for elderly patients.
AB  - OBJECTIVE: Due to the rising number of elderly patients and advances in
      endoscopic devices, early laryngeal and pharyngeal cancers are increasingly found
      in elderly patients. In these cases, minimally invasive endoscopic larygo
      pharyngeal surgery (ELPS) may be indicated. However, the safety and efficacy of
      ELPS in elderly populations has not been established. The purpose of this study
      was to investigate the safety, outcomes and feasibility of ELPS in very elderly
      patients. METHODS: Between February 2010 and April 2016, 29 pharyngeal cancerous
      or pre-cancerous lesions in 19 patients aged 75 years or older were treated with
      ELPS. Twenty-six resections were performed in total, and the patients' clinical
      courses were reviewed. RESULTS: Sixteen patients had multiple comorbidities and
      moderate to severe comorbidities were observed in 17 patients. The average
      surgical time and hospitalization period was 54.3min and 18.8 days, respectively.
      On average, oral intake began 4.4days after the procedure, and all patients
      eventually received nourishment by mouth; no percutaneous endoscopic gastrostomy
      dependency was observed. Complications included post-operative bleeding and
      aspiration pneumonia in two cases each, and all complications were safely
      managed. The 3-year overall survival rate was 90.2% and the 3-year disease
      specific survival rate was 100%. CONCLUSION: ELPS was safely performed in elderly
      patients, suggesting that it is a feasible treatment option for pharyngeal
      lesions in very elderly patients.

PMID- 30205916
TI  - Endolymphatic hydrops severity in magnetic resonance imaging evidences disparate
      vestibular test results.
AB  - OBJECTIVES: It has been suggested that in Meniere's disease (MD) a dissociated
      result in the caloric test (abnormal result) and video head-impulse test (normal
      result) probably indicates that hydrops affects the membranous labyrinth in the
      horizontal semicircular canal (HSC). The hypothesis in this study is that based
      on endolymphatic hydrops' cochleocentric progression, hydrops should also be more
      severe in the vestibule of these patients than in those for whom both tests are
      normal. METHODS: 22 consecutive patients with unilateral definite MD were
      included and classified as NN if both tests were normal or AN if the caloric test
      was abnormal. MRI evaluation of endolymphatic hydrops was carried out with a T2
      FLAIR sequence performed 4h after intravenous gadolinium administration. The
      laterality and degree of vestibular endolymphatic hydrops and the presence or
      absence of cochlear endolymphatic hydrops were recorded. Demographic data,
      audiometric and vestibular evoked myogenic potentials were collected, and video
      head-impulse and caloric tests were performed. RESULTS: Patients in both groups
      (NN and AN) were similar in terms of demographic data and hearing loss. The
      interaural asymmetry ratio was significantly higher for ocular and cervical VEMP
      in patients in the AN group. There was a significantly higher degree of hydrops
      in the vestibule of the affected ear of AN patients (chi2; p=0.028). CONCLUSION:
      Significant canal paresis in the caloric test is associated with more severe
      endolymphatic hydrops in the vestibule as detected with gadolinium-enhanced MRI
      and with a more severe vestibular deficit. LEVEL OF EVIDENCE: 2a.

PMID- 30205917
TI  - Renal Calculus in Floating-Harbor Syndrome: A Case Study.
AB  - Floating-Harbor syndrome is a rare condition marked by short stature and delayed
      bone age, characteristic facial features, and speech impairment. Floating-Harbor
      syndrome commonly results from a sporadic genetic mutation. Renal abnormalities
      have rarely been encountered. We report the first patient with Floating-Harbor
      syndrome who spontaneously passed a renal calculus consisting of calcium oxalate
      monohydrate and calcium oxalate dihydrate. A renal ultrasound showed echotexture
      within the renal pyramids, hydronephrosis, and a cyst. Pediatric nurse
      practitioners should be alert to the unique features associated with Floating
      Harbor syndrome and be prepared to monitor and treat the renal abnormalities that
      may accompany this uncommon condition.

PMID- 30205918
TI  - Vocal Tract Discomfort Scale: Validation of the Argentine Version.
AB  - OBJECTIVE: The objective of this study was to validate the Vocal Tract Discomfort
      Scale (VTD) Argentine version. STUDY DESIGN: Nonrandomized, cross-sectional
      prospective study with control group. MATERIAL AND METHODS: The VTD Scale was
      culturally and linguistically adapted to Argentinian Spanish according to the
      recommended requirements of translation, closely observing the methodology that
      was suggested (translation, summary, review and back-translation). The scale
      Argentine version (Escala de disconfort del tracto vocal) was administered to 107
      patients with muscle-tension dysphonia (MTD) (23 men and 84 women, mean ages
      being: 32.30 +/- 9.09 years old for MTD type I, and 31.23 +/- 8.45 years old for
      MTD type II) and 30 volunteers with no vocal pathology (9 men and 21 women, mean
      ages being: 44.3 +/- 8.72 years old). All patients completed the Escala de
      disconfort del tracto vocal before and after Mathieson Laryngeal Manual Therapy.
      The results of the VTD Scale administered in both patients and vocally healthy
      subjects were initially compared; the changes arising from pre and post therapy
      were also compared in the second phase. The internal consistency of the VTD Scale
      was assessed using Cronbach alpha coefficient. RESULTS: The internal consistency
      assessed was considered acceptable for both subscales within the VTD Scale. The
      values obtained for frequency, severity, and total score of the Scale were
      similar in patients with MTD I and MTD II, marking a difference with those
      obtained in the control group of healthy volunteers. A lump feeling in the throat
      was one of the most frequent symptoms in both MTD and vocally healthy groups.
      CONCLUSION: The VTD Scale shows an acceptable consistency, so it is a highly
      reproducible, reliable, and valuable instrument of evaluation to assess
      Argentinian patients with voice disorders.

PMID- 30205919
TI  - Patient perspectives on how living with a mental illness affects making and
      maintaining healthy lifestyle changes.
AB  - OBJECTIVE: To understand the ways that mental health symptoms interfere with
      achieving health goals. METHODS: Individuals with mental illness diagnoses and
      varying levels of preventive service use were recruited from federally qualified
      health centers and an integrated health care delivery system and interviewed.
      Thematic analysis was used to characterize descriptions of how mental illness
      experiences influenced lifestyle change efforts. RESULTS: Three themes described
      patients' (n = 163) perspectives on barriers to making healthy lifestyle changes:
      1) Thinking about making lifestyle changes is overwhelming for individuals
      already managing the burdens of mental illnesses; 2) Depression makes it
      difficult to care about a healthy future; and 3) When mental illness symptoms are
      not adequately treated unhealthy behaviors that provide relief are unlikely to be
      discontinued. Participants also made suggestions for improving health care
      delivery to facilitate positive behavior change. CONCLUSION: Patients with mental
      illnesses need their clinicians to be empathic, help them envision a healthier
      future, address unmet mental health needs, and provide resources. PRACTICE
      IMPLICATIONS: Primary care clinicians should encourage their patients with mental
      illnesses to make healthy lifestyle changes within the context of a supportive
      relationship. Lifestyle change can be overwhelming; clinicians should acknowledge
      progress and provide ongoing tangible support.

PMID- 30205920
TI  - A cup of magic.
AB  - This reflective piece tells the story of an impactful patient interaction that
      shaped the practice of a medical student. The essay focuses on the power of
      shared time and the development of meaningful relationships as a form of
      adjunctive therapy for patients, regardless of diagnosis or prognosis. Fostering
      an appreciation for the present moment and savoring glimpses of human interaction
      are other themes that are touched upon in this piece.

PMID- 30205921
TI  - [Breast implants: Supply on the French market].
AB  - The choice of an implant by a plastic surgeon is often based on marketing
      arguments, believes, and subjective reasons more than real high level evidence
      basis. Furthermore, we rarely compare manufacturers with each other objectively.
      Therefore our aim was to put together information coming from the different
      companies available in France in a single article.

PMID- 30205922
TI  - Is the Liberal Use of Oxygen Associated With Worse Outcomes Among Critically Ill
      Patients?

PMID- 30205923
TI  - Factors associated with electroencephalographic and clinical remission of benign
      childhood epilepsy with centrotemporal spikes.
AB  - PURPOSE: Benign childhood epilepsy with centrotemporal spikes (BECTS) is strongly
      related to age, both to age at the time of seizure onset and to age at remission.
      However, the age of remission varies. The present study analyzed factors
      associated with remission of BECTS. METHODS: Sixty-nine children with BECTS were
      retrospectively analyzed. Thirty-eight (55.1%) were boys and 31 (44.9%) were
      girls. Mean age at seizure onset was 86.36 +/- 24.55 months (range: 41-151
      months). RESULTS: The mean age at the time of EEG improvement or remission was
      138.31 +/- 19.71 months. Of the 69 patients, 36 (52.2%) exhibited
      electroencephalography (EEG) improvement or remission before age 11.5 years,
      whereas 33 (47.8%) showed later improvement or remission. The two groups differed
      significantly in age at seizure onset. When patients were divided into groups
      using an age cutoff for last seizure of 9 years, the two groups differed
      significantly in age at seizure onset. CONCLUSIONS: The most important predictor
      of early BECTS remission is age at seizure onset.

PMID- 30205924
TI  - An overview of current and emerging devices for percutaneous left atrial
      appendage closure.
AB  - Atrial fibrillation (AF) is common and is a prominent risk factor for ischemic
      stroke. Oral anticoagulant (OAC) therapy has been the main strategy for stroke
      prevention in AF patients; however, OAC therapy carries a bleeding risk and is
      not tolerated by all patients. Left atrial appendage (LAA) closure offers a non
      pharmacological alternative for stroke prevention in patients with non-valvular
      AF. In this update, an overview of current and emerging LAA occluders is given -
      with special attention to the key design features of every single device and, if
      available, preclinical or clinical data.

PMID- 30205925
TI  - [ypT0N0 after neoadjuvant chemotherapy and cystectomy for muscle-invasive bladder
      cancer: Incidence and prognosis. A review from the Bladder group of the French
      Committee of Oncology].
AB  - INTRODUCTION: Neoadjuvant chemotherapy (NAC) is recommended for localized muscle
      invasive bladder cancer when patients are fit for cisplatin-based chemotherapy. A
      pathological complete response can be observed, corresponding to ypT0N0 stage on
      the radical cystectomy specimen. This review discusses the incidence, prognosis
      and potential therapeutic impact of complete response on pathological specimen in
      NAC treated patients. METHODS: A comprehensive review of the literature was
      conducted using Medline database, with no time frame. The articles were selected
      using the following keywords association: "Bladder cancer" (Mesh) AND
      "Neoadjuvant chemotherapy" (Mesh) AND "pT0" (Mesh). RESULTS: After NAC, ypT0N0
      rates vary from 9 to 46% among the series, reported rates that are higher
      compared to those of pT0 without NAC administration. The incidence depends on the
      chemotherapy regimen (maximal local effect with cisplatin-based chemotherapy) and
      the pathological type of the disease (presence of variant histologies). Molecular
      analyses of bladder cancer could probably help in the near future to identify and
      predict NAC responders. Pathological complete response is associated with a
      favorable prognosis in terms of recurrence-free and overall survival.
      Nevertheless, disease recurrences are still observed in 10-15% of cases, which
      underlies the importance of local treatment and close follow-up even in these
      patients. CONCLUSION: ypT0N0 rate is approximately 25% after NAC, that is 4.3
      higher than after bladder resection alone. The prognosis is better than that with
      residual tumor on specimen and is comparable to that of pT0 without NAC
      administration.

PMID- 30205926
TI  - The changes of intraoperative body temperature in adult liver transplantation: A
      retrospective study.
AB  - BACKGROUND: Body temperature is poorly regulated in patients with end-stage liver
      disease. Due to the prolonged surgery time and anhepatic time as well as the
      complex surgical procedures performed in liver transplantation, the body
      temperature fluctuates greatly. This study investigated the effect of
      intraoperative body temperature fluctuations on the prognosis of liver
      recipients. METHODS: The body temperatures of liver recipients recorded from the
      induction of anesthesia (T0) until the end of surgery (T14) were retrieved. The
      patients were divided into two groups: the hypothermia group (< 35  degrees C and
      >= 5 min) and the normothermia group (>= 35  degrees C or < 35  degrees C but < 5
      min). Intraoperative and postoperative variables were compared between the two
      groups, and the correlations between the duration of hypothermia and the medical
      variables were analyzed. RESULTS: Of the 107 patients, 67 patients were in the
      normothermia group, and 40 in the hypothermia group. The lowest body temperature
      was at 5 min after reperfusion for the whole cohort. Compared with the
      normothermia group, patients in the hypothermia group were more prone to
      bleeding, had a longer intubation time and increased rates of bacterial infection
      and acute pulmonary edema after liver transplantation (P < 0.05). Hypothermia
      time was positively correlated with bleeding volume, intubation time, units of
      blood transfusions and intensive care stay, but negatively correlated with urine
      output. CONCLUSIONS: The intraoperative body temperature exhibited a graphical
      "V" trend, and the lowest temperature was at 5 min after reperfusion. The longer
      the duration of hypothermia, the more unfavourable the prognosis.

PMID- 30205927
TI  - A Case of Near-Fatal Drowning Caused by an Attack from a Wild Boar.

PMID- 30205928
TI  - Staff Training Interests, Barriers, and Preferences in Rural and Urban Child Care
      Programs in Minnesota.
AB  - OBJECTIVES: To describe any rural-urban differences in child care providers' (1)
      past training on the facilitation of child healthy eating and physical activity
      and (2) views relevant to the design of trainings. METHODS: Cross-sectional
      analysis of data from the 2016 Healthy Start, Healthy State survey of Minnesota
      child care providers (rural, n = 232; urban, n = 386). Licensed family home-based
      care providers and providers working at licensed centers responded online or by
      mail to measures of desired training content, barriers, and delivery mode
      preferences. RESULTS: Training barriers that were more often a concern for rural
      compared with urban providers included scheduling outside work hours,
      difficulties finding trainings, and travel (all P < .001). Rural and urban
      providers identified similar preferences with regard to training content and
      delivery. CONCLUSIONS AND IMPLICATIONS: The findings suggest it would be
      worthwhile for future research to examine whether rural providers' training
      participation is affected by uniquely relevant participation barriers.

PMID- 30205929
TI  - Using Theory to Evaluate the Implementation and Integration of an Expanded School
      Breakfast Program in Rural Midwestern High Schools.
AB  - OBJECTIVE: Use Normalization Process Theory to evaluate the implementation and
      integration of the expanded School Breakfast Program (SBP). DESIGN: Interviews
      were conducted during the 2014-2015 school year. Normalization Process Theory
      guided the interview questions. SETTING: Rural high schools in Minnesota.
      PARTICIPANTS: Interviews were conducted with 12 foodservice directors and 11
      principals from the Project Break-Fueling Academics and Strengthening Teens
      intervention. Four of the 12 schools were in their first year of providing the
      expanded SBP program to their students whereas 8 were in their second year.
      PHENOMENON OF INTEREST: Normalization Process Theory was used to evaluate the
      implementation and integration of the expanded SBP into rural Midwestern high
      schools. ANALYSIS: Three members of the research team used NVivo 10 software to
      code and analyze the interviews. Emerged themes were reported. RESULTS: Modifying
      the SBP aligned with values of the study participants (coherence). Support was
      obtained from staff, students, and community members (cognitive participation).
      Operational work occurred in each school to establish and integrate the modified
      SBP (collective action). The SBP expansion was assessed through student
      participation rates (reflexive monitoring). CONCLUSIONS AND IMPLICATIONS:
      Normalization Process Theory can be used to evaluate the implementation,
      embedding, and integration of a modified SBP into a school program. This
      evaluation can support other schools in modifying and embedding their SBPs into
      their school environment.

PMID- 30205930
TI  - Doxorubicin-Induced Myocardial Fibrosis Involves the Neurokinin-1 Receptor and
      Direct Effects on Cardiac Fibroblasts.
AB  - BACKGROUND: Cancer patients receiving anthracycline-based chemotherapy (Anth-bC)
      may experience early cardiac fibrosis, which could be an important contributing
      mechanism to the development of impaired left ventricular (LV) function.
      Substance P, a neuropeptide that predominantly acts via the neurokinin 1 receptor
      (NK-1R), contributes to adverse myocardial remodelling and fibrosis in other
      cardiomyopathies. We sought to determine if NK-1R blockade is effective against
      doxorubicin (Dox - a frequently used Anth-bC)-induced cardiac fibrosis and
      cardiomyocyte apoptosis. In addition, we explored the direct effects of Dox on
      cardiac fibroblasts. METHODS: Male Sprague-Dawley rats were randomised to receive
      saline, six cycles of Dox (1.5mg Dox/kg/cycle) or Dox with an NK-1R antagonist
      (L732138, 5mg/kg/daily through Dox treatment). At 8 weeks after the initial dose
      of Dox, LV function and histopathological myocardial fibrosis and cell apoptosis
      were assessed. Collagen secretion was measured in vitro to test direct Dox
      activation of cardiac fibroblasts. RESULTS: Rats undergoing Dox treatment (9mg/kg
      cumulative dose) developed cardiac fibrosis and cardiomyocyte apoptosis. NK-1R
      blockade partially mitigated cardiac fibrosis while completely preventing
      cardiomyocyte apoptosis. This resulted in improved diastolic function.
      Furthermore, we found that Dox had direct effects on cardiac fibroblasts to cause
      increased collagen production and enhanced cell survival. CONCLUSIONS: This study
      demonstrates that cardiac fibrosis induced by Anth-bC can be reduced by NK-1R
      blockade. The residual fibrotic response is likely due to direct Dox effects on
      cardiac fibroblasts to produce collagen.

PMID- 30205931
TI  - Emerging Trends in Cannabis Administration Among Adolescent Cannabis Users.
AB  - PURPOSE: The legal landscape of cannabis availability and use in the United
      States is rapidly changing. As the heterogeneity of cannabis products and methods
      of use increases, more information is needed on how these changes affect use,
      especially in vulnerable populations such as youth. METHODS: A national sample of
      adolescents aged 14-18 years (N = 2,630) were recruited online through
      advertisements displayed on Facebook and Instagram to complete a survey on
      cannabis. The survey assessed patterns of edible use, vaping, and smoking
      cannabis, and the associations among these administration routes and use of other
      substances. RESULTS: The most frequent and consistent route of cannabis use was
      smoking (99% lifetime), with substantial numbers reporting vaping (44% lifetime)
      and edible use (61% lifetime). The majority of those who had experimented with
      multiple routes of cannabis administration continued to prefer smoking, and the
      most common pattern of initiation was smoking, followed by edibles and then
      vaping. In addition to cannabis use, adolescents reported high rates of nicotine
      use and substantial use of other substances. Adolescents who used more cannabis
      administration routes tended to also report higher frequency of other substances
      tried. CONCLUSIONS: Additional work is needed to determine whether the observed
      adolescent cannabis administration patterns are similar across different samples
      and sampling methods as well as how these trends change over time with extended
      exposure to new products and methods. The combined knowledge gained via diverse
      sampling strategies will have important implications for the development of
      regulatory policy and prevention and intervention efforts.

PMID- 30205932
TI  - Factors Impacting Implementation of Evidence-Based Strategies to Create Safe and
      Supportive Schools for Sexual and Gender Minority Students.
AB  - PURPOSE: The Centers for Disease Control and Prevention recommends six evidence
      based strategies to improve safety and support for sexual and gender minority
      (SGM) youth in U.S. schools. However, only a small minority of schools implement
      all strategies. This study draws on implementation science to assess contextual
      challenges to strategy implementation. METHODS: Semistructured interviews were
      conducted with at least two stakeholders at each of 42 high schools in New
      Mexico. Interviews consisted of open-ended questions centered on attitudes
      toward, access to, and availability of school and community supports for SGM
      youth, school policies, and practices, and organizational factors believed to
      impact implementation. Transcripts were imported into NVivo 11 for iterative
      coding and qualitative analysis. RESULTS: We identified eleven overarching sets
      of factors related to the preparedness of schools to implement the evidence-based
      strategies: (1) political climate; (2) community context; (3) community
      resources; (4) policies and practices; (5) staff knowledge and exposure to SGM
      issues; (6) training deficits; (7) prevalence of neutrality discourses suggesting
      SGM students should not be singled out for "special treatment" or intervention;
      (8) student attitudes and support; (9) de facto safe spaces; (10) health
      education curricula; and (11) pragmatic considerations, such as time, staff
      turnover, and workloads. Key factors believed to hinder implementation included
      lack of resources, staffing concerns, and knowledge deficits. CONCLUSIONS: These
      results can be used to inform the development of implementation strategies to
      modify school health systems from within to best support evidence-based practices
      for SGM youth and other stigmatized populations.

PMID- 30205933
TI  - Statin-naive anti-HMGCR antibody-mediated necrotizing myopathy in China.
AB  - This study aimed to clarify the phenotypes and therapeutic responses of statin
      naive anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibody
      mediated necrotizing myopathy. Anti-HMGCR antibodies were tested with ELISA
      methodology in the sera sample of 98 patients meeting the idiopathic inflammatory
      myopathy criteria and with negative anti-signal recognition particle (SRP)
      antibody. Twenty-one statin-naive patients with anti-HMGCR antibody were detected
      (21.4%), with onset age from 6 to 67 years old. Proximal weakness and neck
      flexion weakness was the core neurological feature. The average maximal creatine
      kinase (CK) level was 7968.6 +/- 4408.7U/L. Muscle MR imaging showed edema
      (88.2%), moderate or severe fatty replacement (70.6%) and muscle atrophy (88.2%)
      in lower limbs. Fatty replacement was significantly more prominent in the medial
      and posterior musculature than the anterior musculature (p = 0.0013). Seven
      (33.3%) patients were treated with mono-glucocorticoid, and thirteen (61.9%)
      patients needed adjuvant immunosuppressant. Eight (38.1%) patients experienced
      symptom relapse. The early-onset patients (<50 years old) were found with higher
      CK levels, shorter duration course, poorer response to adjuvant immunosuppressant
      and more recurrent weakness than the late-onset patients (>=50 years old). As a
      conclusion, Statin-naive anti-HMGCR antibody-mediated necrotizing myopathy may
      not be rare. Compared with late-onset statin-naive patients with anti-HMGCR
      antibody-mediated necrotizing myopathy, early-onset patients presented severer
      clinical features and worse therapeutic responses.

PMID- 30205934
TI  - Aromatherapy for Preoperative Anxiety: A Pilot Study.
AB  - PURPOSE: The aim of this study was to evaluate the use of a lavender aromatherapy
      skin patch on anxiety and vital sign variability during the preoperative period
      in female patients scheduled for breast surgery. DESIGN: This observational pilot
      study used a one-group, pretest and post-test design. METHODS: Participants
      received an aromatherapy patch in addition to standard preoperative care. Anxiety
      levels were assessed with a 10-cm visual analog scale at baseline and then every
      15 minutes after patch placement. Vital sign measurements were recorded at the
      same interval. FINDINGS: There was a statistically significant decrease (P = .03)
      in the anxiety visual analog scale measurements from baseline to final scores.
      CONCLUSIONS: Findings from this study suggest the use of aromatherapy is
      beneficial in reducing anxiety experienced by females undergoing breast surgery.
      Further research is needed to address the experience of preoperative anxiety,
      aromatherapy use, and the challenges of managing preoperative anxiety.

PMID- 30205935
TI  - Bach to the Basics: Implementation and Impact of a Postoperative, Inpatient
      Personalized Music Program for Older Adults.
AB  - PURPOSE: Music as an intervention to mitigate pain and anxiety has been well
      studied in the perioperative period. We present a quality improvement (QI) report
      describing implementation and evaluation of a postoperative, inpatient
      personalized music program for older adults undergoing elective surgeries.
      DESIGN: We embedded this program in an existing interdisciplinary perioperative
      care program, with an outpatient and an inpatient component, at an academic
      institution. METHODS: We describe our initial QI steps, highlight critical
      lessons learned from this behavioral intervention, and discuss high yield areas
      to focus on future implementation efforts. FINDINGS: Rapid cycle improvement was
      an effective method to monitor QI measures. Participants in our program perceived
      improved mood and pain control, were satisfied with their experience, and had
      lower rates of incident delirium. CONCLUSIONS: This program offers perioperative
      teams, especially frontline nursing staff, an inexpensive, patient-centered tool
      to optimize postoperative pain and anxiety. We believe that it can be easily
      replicated at a variety of hospital systems.

PMID- 30205936
TI  - Rasagiline monotherapy in early Parkinson's disease: A phase 3, randomized study
      in Japan.
AB  - BACKGROUND: Rasagiline is a monoamine oxidase type-B inhibitor in development in
      Japan for Parkinson's disease (PD). The objective of this Phase 3, randomized,
      double-blind study was to evaluate the efficacy and safety of rasagiline in
      Japanese patients with early PD (NCT02337725). METHODS: Patients were 30-79 years
      old with a diagnosis of PD within 5 years. Following a two-week placebo run-in
      period, patients were randomized 1:1 to receive rasagiline (1 mg/day) or placebo
      for up to 26 weeks. The primary endpoint was change from baseline in the MDS
      UPDRS Part II + III total score (TS). Secondary endpoints included the MDS-UPDRS
      Parts II + III, III, II, and I TS and safety. RESULTS: In total, 118 patients
      were randomized to rasagiline and 126 to placebo. Patient characteristics at
      baseline were similar in both groups. The change from baseline in the MDS-UPDRS
      Part II + III TS was significantly greater in the rasagiline vs. placebo group
      (rasagiline-placebo: -6.39, 95% CI: -8.530, -4.250; P < 0.0001). The mean changes
      from baseline in the MDS-UPDRS Part II + III, Part III and Part II TS were lower
      at treatment visits between weeks 6 and 26 in the rasagiline vs. placebo groups.
      The overall incidence of treatment-emergent adverse events (TEAEs) was 62.4% and
      52.4% in the rasagiline and placebo groups, respectively; most frequent TEAE was
      nasopharyngitis (15.4% and 15.1%). CONCLUSION: Treatment with oral rasagiline 1
      mg/day was effective and well-tolerated in Japanese patients with early PD, with
      a significantly greater improvement in the MDS-UPDRS Part II + III TS vs.
      placebo, and a similar safety profile.

PMID- 30205937
TI  - Rate and age-dependent damage elasticity formulation for efficient hip fracture
      simulations.
AB  - Prediction of bone failure is beneficial in a range of clinical situations from
      screening of osteoporotic patients with high fracture risk to assessment of
      protective equipment against trauma. Computational efficiency is an important
      feature to consider when developing failure models for iterative applications,
      such as patient-specific diagnosis or design of orthopaedic devices. The authors
      previously developed a methodology to generate efficient mesoscale structural
      full bone models. The aim of this study was to implement a damage elasticity
      formulation representative of an elasto-plastic material model with age and
      strain rate dependencies compatible with these structural models. This material
      model was assessed in the prediction of femoral fractures in longitudinal
      compression and side fall scenarios. The simulations predicted failure loads and
      fracture patterns in good agreement with reported results from experimental
      studies. The observed influence of strain rate on failure load was consistent
      with literature. The superiority of a simplified elasto-plastic formulation over
      an elasto-brittle bone material model was assessed. This computationally
      efficient damage elasticity formulation was capable of capturing fracture
      development after onset.

PMID- 30205938
TI  - Should the Extended Lateral Approach Remain Part of Standard Treatment in
      Displaced Intra-articular Calcaneal Fractures?
AB  - The aim of this study was to evaluate the results of open reduction and internal
      fixation through the extended lateral approach (ELA) in displaced intra-articular
      calcaneal fractures and to determine whether this approach should remain part of
      standard therapy. This retrospective cohort study included 60 patients with 64
      displaced intra-articular calcaneal fractures who underwent surgical treatment
      through the ELA. Outcome measures were the visual analog scale foot and ankle
      (VAS FA), the American Orthopedic Foot and Ankle Society (AOFAS) score, surgical
      site infections (SSIs), and reoperations. We determined the AOFAS score for 40
      patients with 42 fractures, and 42 patients with 44 fractures completed the VAS
      FA questionnaire. The mean VAS FA score was 61.0 +/- 23.4 and the median AOFAS
      score was 83 (range 33 to 100), with 55% good to excellent scores. We found 10.9%
      superficial SSIs successfully treated with antibiotics. In 4.7% of patients a
      deep SSI was diagnosed, wherefore premature implant removal was necessary.
      Patients with an SSI did not have significantly lower VAS FA or AOFAS scores than
      did patients without an SSI (p = .318 and p = .766, respectively). Implant
      removal in absence of SSIs was necessary in 17 patients because of pain, and 3
      patients needed secondary arthrodesis because of persistent pain. We concluded
      that the ELA proved to be a safe procedure, and moreover the most common
      complications did not influence the long-term outcomes of patients. However,
      recent literature demonstrates that less invasive techniques seem to exceed the
      ELA with respect to wound complications.

PMID- 30205939
TI  - Mental status evaluation in older adults with cancer: Development of the Mental
      Health Index-13.
AB  - OBJECTIVES: The Mental Health Index (MHI) is widely used as a measure of mental
      health status, but has not been evaluated in the geriatric oncology population.
      This study evaluated the MHI-17 in a geriatric oncology population, to establish
      validity and scoring rules. MATERIALS AND METHODS: The Carolina Senior Registry
      (NCT01137825) was used to obtain data for 686 patients with cancer 65 and older
      who completed the MHI-17. The 17-item patient-reported measure produces one total
      score summing across four domains: anxiety, depression, positive affect, and
      sense of belonging. Cronbach's alpha (alpha), confirmatory factor analyses (CFA),
      item-response theory (IRT) analyses, and differential item functioning (DIF)
      analyses were used to evaluate internal consistency and validity. RESULTS AND
      DISCUSSION: The revised MHI retained the 13 best-fitting items from the MHI-17
      and resulted in a final model that included two subscales: anxiety (four items,
      RMSEA 0.11; CFI 0.99; TLI 0.98) and depression (9 items, RMSEA 0.10; CFI 0.96; TL
      0.95). IRT analyses of the four anxiety items indicated good fit (RMSEA 0.08) and
      precise measurement of adults with poor mental health, and the nine depression
      items also fit well (RMSEA 0.05). No meaningful differences were found by sex,
      education, or treatment stage. Scores were developed to provide meaningful norms.
      The new MHI-13 is a shorter, more accurate way to assess mental health in older
      adults with cancer and most importantly allows clinicians to separately identify
      anxiety and/or depression - a clinically important distinction as treatment
      differs among these two types of mental health impairment.

PMID- 30205940
TI  - Comment on: Single-stage conversions from failed gastric band to sleeve
      gastrectomy versus Roux-en-Y gastric bypass: a closer look.

PMID- 30205941
TI  - Comment on: diagnostic value of computed tomography for detecting anastomotic or
      staple line leakage after bariatric surgery.

PMID- 30205942
TI  - Niemann-Pick type C disease: The atypical sphingolipidosis.
AB  - Niemann-Pick type C (NPC) disease is a lysosomal storage disorder resulting from
      mutations in either the NPC1 (95%) or NPC2 (5%) genes. NPC typically presents in
      childhood with visceral lipid accumulation and complex progressive
      neurodegeneration characterized by cerebellar ataxia, dysphagia, and dementia,
      resulting in a shortened lifespan. While cholesterol is widely acknowledged as
      the principal storage lipid in NPC, multiple species of sphingolipids accumulate
      as well. This accumulation of sphingolipids led to the initial assumption that
      NPC disease was caused by a deficiency in a sphingolipid catabolism enzyme,
      similar to sphingomyelinase deficiencies with which it shares a family name. It
      took about half a century to determine that NPC was in fact caused by a
      cholesterol trafficking defect, and still as we approach a century after the
      initial identification of the disease, the mechanisms by which sphingolipids
      accumulate remain poorly understood. Here we focus on the defects of sphingolipid
      catabolism in the endolysosomal compartment and how they contribute to the
      biology and pathology observed in NPC disease. This review highlights the need
      for further work on understanding and possibly developing treatments to correct
      the accumulation of sphingolipids in addition to cholesterol in this currently
      untreatable disease.

PMID- 30205943
TI  - Building the Case for Quality Improvement.
AB  - Great improvements have been made by quality improvement teams. National trends
      towards using quality and value metrics in reimbursement suggest that physicians
      and advanced practitioners caring for children and adolescents will benefit from
      knowing and using quality improvement methods. These methods will also help as
      transparency of quality data becomes more commonplace.

PMID- 30205944
TI  - Process Mapping - The Foundation for Effective Quality Improvement.
AB  - Process maps are a key quality improvement tool used to visualize how healthcare,
      and its complex processes, are delivered. It is used for determining the step by
      step flow of the process, its timing, handoffs, and identifying outputs that can
      be visualized, measured, and studied. Due to the complexity of healthcare,
      process mapping must be a foundational element of both healthcare process design
      and quality improvement.

PMID- 30205945
TI  - Understanding Variation: Part1- the Run Chart.
AB  - This paper briefly describes different types of data, how to collect data, the
      rationale for organizing data in a time-ordered fashion, and how to use a simple
      tool called a run chart to present and analyze data. The run chart is simple to
      construct and equally as simple to analyze. Run charts make variation visible and
      determine whether a change has made an improvement and if the improvement is
      being sustained. Two probability rules accompany run charts to help answer the
      question "How will we know that a change is an improvement?". These rules provide
      an objective statistical threshold to determine whether changes from quality
      improvement efforts are having an impact. Quality improvement and data go hand-in
      hand. To qualify as quality improvement, projects should have a well-developed
      data collection and analysis strategy. A run chart and the rules presented in the
      following paper are simple, statistically valid tools used to answer the question
      "How will we know that a change is an improvement?".

PMID- 30205946
TI  - Fixed Drug Eruption Due to Chlorhexidine Mouthwash Confirmed by Lesional Patch
      Testing.

PMID- 30205947
TI  - Bioarchaeological evidence of care provided to a physically disabled individual
      from Pachacamac, Peru.
AB  - This paper presents a bioarchaeology of care case study based on the skeletonized
      remains of an elderly female with a congenital condition that compromised both
      mobility and independence in undertaking certain basic tasks, and which generated
      requirements for long-term care in the form of both direct support and
      accommodation. The remains show evidence of bilateral cervical ribs, severe
      osteoarthritic destruction in the right shoulder joint, and a healed skull
      trepanation. The remains were recovered from a cemetery dating to the initial
      part of the Late Intermediate Period at the archaeological site of Pachacamac,
      Peru. The subject has been identified as belonging to an Ychsma ayllu. This paper
      applies the bioarchaeology of care methodology in considering the implications of
      care provision within the Ychsma socialcontext, and suggests that caregiving may
      have been a relatively common practice in this complex society. This case study
      is a good example of how the application of social theory through the
      bioarchaeology of care approach can enrich bioarchaeological studies.

PMID- 30205949
TI  - Current status of zirconia implants in dentistry: preclinical tests.
AB  - PURPOSE: This systematic review aimed to provide an overview of zirconia implants
      as well as regarding the outcome of the implant-restorative complex in
      preclinical studies. STUDY SELECTION: An electronic search of the literature
      prior to July 2017 was performed to identify all articles related to preclinical
      research on zirconia implants. The search was conducted using MEDLINE (National
      Library of Medicine) and PubMed without restrictions concerning the date of
      publication. The search terminology included: zirconia implant, osseointegration,
      bone-to-implant contact, soft tissue, histology, histomorphometry, surface
      modification, surface roughness, surface characteristics, and restoration
      (connecting multiple keywords with AND, OR). RESULTS: Fifty-seven studies were
      finally selected from an initial yield of 654 titles, and the data were
      extracted. The identified preclinical studies focused on several aspects related
      to zirconia implants, namely biocompatibility, mechanical properties, implant
      design, osseointegration capacity, soft tissue response, and restorative options.
      Due to heterogeneity of the studies, a meta-analysis was not possible. The most
      frequently used zirconia material for the fabrication of implants is yttria
      stabilized tetragonal zirconia polycrystal. The resistance-to-fracture for
      zirconia implants ranged between 516-2044N. The mostly investigated parameter was
      osseointegration, which is compared to that of titanium. A lack of evidence was
      found with other parameters. CONCLUSIONS: Due to its good biocompatibility as
      well as favorable physical and mechanical properties, zirconia implants are a
      potential alternative to titanium implants. However, knowledge regarding the
      implant-restorative complex and related aspects is still immature to recommend
      its application for daily practice.

PMID- 30205948
TI  - Prognostic Implications of Mucinous Differentiation in Metastatic Colorectal
      Carcinoma Can Be Explained by Distinct Molecular and Clinicopathologic
      Characteristics.
AB  - BACKGROUND: The mucinous histologic subtype accounts for 5% to 20% of colorectal
      cancer (CRC) cases but remains poorly characterized. The present study
      characterized the baseline characteristics, mutational profile, and clinical
      outcomes of patients diagnosed with mucinous CRC. MATERIALS AND METHODS: We
      identified 1877 patients with metastatic CRC with available histologic findings
      and molecular profiling and summarized the baseline clinical and pathologic
      characteristics and overall survival (OS) stratified by the histologic type. The
      data from separate cohorts with consensus molecular subtype (CMS) and CpG island
      methylator information were also summarized. RESULTS: The mucinous histologic
      type was found in 277 of the 1877 patients (14.8%) and was associated with an
      increased prevalence of microsatellite instability (P < .001) and a right-sided
      primary (P < .001). An increased frequency of CMS1 (microsatellite instability
      immune) and lower rates of CMS2 (canonical) were identified, with mucinous
      compared with nonmucinous adenocarcinoma (P < .0001). Mutations in SMAD4 (P <
      .001), GNAS (P < .001), ERBB2 (P = .02), BRAF (P < .001), and KRAS (P < .001)
      occurred at greater frequencies in the mucinous CRC cases, and TP53 (P < .001),
      APC (P < .001), and NRAS mutations (P = .03) were less common. Univariate (hazard
      ratio [HR], 1.38; 95% confidence interval [CI], 1.17-1.63; P < .001) and
      multivariate analysis (HR, 1.36; 95% CI, 1.12-1.64; P = .002) demonstrated that
      the mucinous histologic type is associated with worse OS. The features associated
      with the mucinous histologic subtype were independent predictors for shorter OS,
      including BRAF (HR, 1.74; 95% CI, 1.35-2.25; P < .001) and KRAS (HR, 1.42; 95%
      CI, 1.22-1.65; P < .001) mutations, right-sided location (HR, 1.20; 95% CI, 1.04
      1.39; P = .01), and synchronous metastases (HR, 2.92; 95% CI, 2.49-3.42; P <
      .001). CONCLUSION: Compared with nonmucinous adenocarcinoma, the mucinous
      histologic type is associated with a worse prognosis, even when controlling for
      known prognostic features. This unique biologic behavior should be considered in
      the treatment and prognostic assessment of patients with CRC.

PMID- 30205951
TI  - Involvement of different neuronal components in the induction of cortical
      plasticity with associative stimulation.
AB  - BACKGROUND: Paired associative stimulation (PAS), with stimulus interval of 21.5
      or 25 ms, using transcranial magnetic stimulation in the posterior-anterior (PA)
      current direction, produces a long-term-potentiation-like effect. Stimulation
      with PA directed current generates both early and late indirect (I)-waves while
      that in anterior-posterior (AP) current predominantly elicits late I-waves. Short
      interval intracortical inhibition (SICI) inhibits late I-waves but not early I
      waves. OBJECTIVE: To investigate how cortical inhibition modulates the effects of
      PAS. METHODS: PAS at stimulus interval of 21.5 ms conditioned by SICI (SICI-PAS)
      was compared to PAS alone with both PA and AP directed currents. RESULTS: PAS
      with both current directions increased cortical excitability. SICI-PAS increased
      cortical excitability in the PA but not the AP current direction. CONCLUSIONS:
      Both early and late I-waves circuits can mediate cortical PAS plasticity under
      different conditions. Plasticity induction with the late but not the early I-wave
      circuits is blocked by SICI.

PMID- 30205950
TI  - Meditation-induced modulation of brain response to transcranial magnetic
      stimulation.

PMID- 30205952
TI  - Prognostic stratification of resected pancreatic ductal adenocarcinoma: Past,
      present, and future.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is the digestive cancer with the poorest
      prognosis, with a 5-year overall survival rate of 7%. Complete surgical resection
      followed by adjuvant chemotherapy is the only treatment with curative intent.
      However, many patients with an apparently localized disease who may undergo
      primary tumor resection already have micro-metastatic disease and will promptly
      develop metastases. Considering the significant rate of morbidity and mortality
      upon pancreatic surgery, the pre-operative identification of patients with an
      aggressive disease is therefore a major clinical issue. Although tumor size,
      differentiation, margins, and lymph node invasion are the main "classical"
      prognostic factors, they are not sufficient to fully predict early disease
      recurrence. In the last decade, multi-omics high-throughput analyses have
      provided a new insight into PDAC biology and have led to the description of
      multiple molecular subtypes, with a significant prognostic value for most of
      them, but that have not yet been transposed to routine clinical practice, mainly
      due to poor availability of tumor tissue material prior to surgical resection. In
      this review, we provide an overview of the current status of clinico-pathological
      and molecular biomarkers (tumor and blood) to predict early recurrence, and their
      implications for clinical practice and future research development.

PMID- 30205953
TI  - Acetylation of lysine residues in the recombinant nucleoprotein and VP40 matrix
      protein of Zaire Ebolavirus by eukaryotic histone acetyltransferases.
AB  - Acetylation of histones and other proteins plays crucial roles in transcriptional
      regulation, chromatin organization, and other biological processes. It has been
      recently reported that the nucleoprotein (NP) of influenza virus is acetylated in
      infected cells, and this modification contributes to the RNA polymerization
      activity of the virus. As the influenza virus, the Ebolavirus contains single
      stranded negative-sense RNA as its viral genome, which interacts with NP and
      other viral proteins. In this study, we performed a series of biochemical
      experiments and revealed that the recombinant Ebolavirus NP and the viral matrix
      protein VP40, which binds with NP, were acetylated by eukaryotic histone
      acetyltransferases, such as P300/CREB-binding protein (P300/CBP) and P300/CBP
      associated factor (PCAF), in vitro. Mass spectrometry was used to identify the
      lysine residues that were potential acetylation targets in NP and VP40. The
      identified lysine residues in NP were located in the RNA-binding cleft and the
      VP35-binding domain. Potentially acetylated lysine targets in VP40 were
      identified in the basic patch, which is necessary for constructing oligomers.
      These results suggest that the acetylation of these lysine residues is involved
      in the interactions between viral proteins.

PMID- 30205955
TI  - Statistical optimization of culture medium to produce recombinant viral protein
      by Escherichia coli host for diagnostic kit to detect human immunodeficiency
      virus (HIV) infection.
AB  - The maximal production of recombinant HIV1 gp41 by E. coli was examined in
      optimal culture condition and medium compositions. The culture condition such as
      growth, initial medium pHs, IPTG concentrations, induction times, temperature
      (0.5 OD, 7.6, 0.75 mM, 4.6 h, 32  degrees C respectively), and yeast extract
      (7.51 g/l), tryptone (7.26 g/l), glucose (2.45 g/l), NaCl (20.40 g/l), betaine
      (10.41 mM) and ampicillin (71.23 MUg/ml) was optimized using statistical
      experimental design and response surface method (RSM). One of the main popular
      methods to attain high cell density in fed-batch culture is by controlling the
      nutrient feeding, which is often necessary for high yield in protein (0.63-0.72
      mg/l) and cell (1.7-2 g/l) of the desired product in four litter fermentations.

PMID- 30205954
TI  - Indoxyl glucuronide, a protein-bound uremic toxin, inhibits hypoxia-inducible
      factor-dependent erythropoietin expression through activation of aryl hydrocarbon
      receptor.
AB  - Renal anemia is common among chronic kidney disease (CKD) patients, and is mainly
      caused by inadequate erythropoietin (EPO) production from kidneys due to
      dysfunction of intracellular hypoxia-inducible factor (HIF) signaling in renal
      EPO-producing cells. We have previously shown that indoxyl sulfate (IS), a
      representative protein-bound uremic toxin accumulated in the blood of CKD
      patients, inhibits hypoxia-induced HIF activation and subsequent EPO production
      through activation of aryl hydrocarbon receptor (AHR). In this study, we further
      investigated the effects of other protein-bound uremic toxins on HIF-dependent
      EPO expression using EPO-producing HepG2 cells. We found that indoxyl glucuronide
      (IG) and IS, but not p-cresyl sulfate, phenyl sulfate, 3-indoleacetic acid or
      hippuric acid, inhibited hypoxia mimetic cobalt chloride-induced EPO mRNA
      expression. Furthermore, IG at concentrations similar to the blood levels in CKD
      patients inhibited the transcriptional activation of HIF induced by both cobalt
      chloride treatment and hypoxic culture. IG also induced CYP1A1 mRNA expression
      and nuclear translocation of AHR protein, indicating that IG activates AHR
      signaling. Blockade of AHR by a pharmacological antagonist CH-223191 abolished
      the IG-induced inhibition of HIF activation. Collectively, this study is the
      first to elucidate the biological effects of IG to inhibit HIF-dependent EPO
      production through activation of AHR. Our data suggests that not only IS but also
      IG contributes to the impairment of HIF signaling in renal anemia.

PMID- 30205956
TI  - Activation of autophagy contributes to the renoprotective effect of
      postconditioning on acute kidney injury and renal fibrosis.
AB  - Ischemia/Reperfusion injury contributes to acute kidney injury (AKI) and
      subsequent chronic kidney disease (CKD) including renal fibrosis. Autophagy is a
      cytoplasmic components degradation pathway that has complex function in the
      development of various diseases such as fibrosis in kidney. Our previous work
      demonstrated that postconditioning (POC) showed excellent therapeutic effect on
      renal fibrosis via inhibiting the overproduction of reactive oxygen species (ROS)
      after reperfusion. But the connection of autophagy and POC in the renoprotective
      effect remains unclear. Here, we defined the relevance of autophagy and POC in
      the protective effect on AKI and subsequent renal fibrosis. We found that at two
      days after I/R injury, POC largely reduced renal tubular epithelial cell
      apoptosis and improved renal function; autophagy was significantly activated in
      kidneys of the POC rats. At two months after reperfusion, the I/R injury rats
      displayed severe renal fibrosis and epithelial-mesenchymal transition (EMT),
      whereas these were remarkably attenuated in the POC treated rats. Overall, our
      results demonstrated that POC could reduce renal damage and attenuate the degree
      of EMT after I/R injury via enhanced activation of autophagy.

PMID- 30205957
TI  - Multiple mutations in the aglycone binding pocket to convert the substrate
      specificity of dalcochinase to linamarase.
AB  - Dalcochinase from Dalbergia cochinchinensis Pierre and linamarase from Manihot
      esculenta Crantz are beta-glucosidases which share 47% sequence identity, but
      show distinct substrate specificities in hydrolysis and transglucosylation.
      Previously, three amino acid residues of dalcochinase, namely I185, N189 and
      V255, were identified as being important for determining substrate specificity.
      In this study, kinetic analysis of the ensuing double and triple mutants of
      dalcochinase showed that only those containing the 185A mutation could
      appreciably hydrolyze linamarin as well as transfer glucose to 2-methyl-2
      propanol. So, the space provided by the I185A mutation appeared to be a
      prerequisite for accommodation of the aglycone moiety containing three
      substituents at the carbinol carbon. However, quantitative analysis of the energy
      parameters revealed mostly antagonistic interactions between these mutations. In
      addition, the N189F mutant showed a potential for use in enzymatic synthesis of
      alkyl glucosides via transglucosylation and reverse hydrolysis reactions. Thus,
      substitution of only 2-3 key residues in the aglycone binding pocket of
      dalcochinase could convert its specificities to that of linamarase, as well as to
      be suitable for any chosen hydrolytic or synthetic applications.

PMID- 30205959
TI  - Global identification of circular RNAs in chronic myeloid leukemia reveals
      hsa_circ_0080145 regulates cell proliferation by sponging miR-29b.
AB  - Circular RNAs (circRNAs) are a class of non-coding RNAs that participate in
      various biological processes and disease pathogenesis. However, the role of
      circRNAs in chronic myeloid leukemia (CML) remains largely unknown. In this
      study, high-throughput sequencing was performed to explore the expression profile
      of circRNAs in CML patients for the first time, and a large number of
      differentially expressed circRNAs were identified. In addition, we constructed
      potential circRNA-miRNA interaction networks in CML, including a detailed
      hsa_circ_0080145-mediated competing endogenous RNA (ceRNA) regulatory network.
      Furthermore, functional experiments demonstrated that hsa_circ_0080145 knockdown
      significantly suppressed CML cell proliferation and hsa_circ_0080145 regulated
      CML cell proliferation by acting as an miR-29b sponge.

PMID- 30205958
TI  - Long non-coding RNA EPIC1 promotes cholangiocarcinoma cell growth.
AB  - Cholangiocarcinoma (CCA) is the as the most frequently observed biliary tract
      malignancy, which has low survival rate in addition to constrained treatment
      options. However, the fundamental molecular mechanism underlying malignant
      progression of CCA is quite ambiguous. Recent studies reported that long non
      coding RNA (lncRNA) might play critical roles in regulating chemo-resistant of
      multiple types of cancer. In this study, our results indicate that the LncRNA
      EPIC1 expression were significantly increased in cholangiocarcinoma tissues,
      compared to adjacent normal tissues. And also, its expression also increased in
      several CCA cancer cell lines than that in human normal immortalized
      cholangiocyte cell. Loss-and-gain of Lnc-EPIC1 contributes to the CCA cell
      growth, colony formation, cell apoptosis and also cell cycle. Myc has been
      reported to directly interact with Lnc-EPIC1 in several cancer cells. Myc
      targets, including Cyclin A/D and CDK9 were downregulated by Lnc-EPIC1 siRNA. Myc
      knockout also suppresses the CCA cell growth, colony formation and cell
      apoptosis. However, Lnc-EPIC1 knockdown failed to enhance the Myc-KO-induced
      suppression of CCA tumor progression. RNA immunoprecipitation (RIP) results
      showed the direct interaction between Lnc-EPIC1 and Myc. Taken together, our
      results show that Lnc-EPIC1 promotes CCA cancer progression by targeting Myc.

PMID- 30205960
TI  - ATP enhances at low concentrations but dissolves at high concentrations liquid
      liquid phase separation (LLPS) of ALS/FTD-causing FUS.
AB  - ATP is the universal energy currency but mysteriously its cellular concentration
      is much higher than that needed for providing energy. Recently ATP was decoded to
      act as a hydrotrope to dissolve liquid-liquid phase separation (LLPS) of FUS
      whose aggregation leads to ALS/FTD. By DIC microscopy and NMR, here we
      characterized the effect of ATP on LLPS of FUS and its N-/C-terminal domains.
      Very unexpectedly, we found that like nucleic acids, ATP enhances LLPS of FUS at
      low but dissolves at high concentrations. Intriguingly, ATP monotonically
      dissolves LLPS of NTD, while it induces LLPS of CTD at low but dissolves at high
      concentrations. Our study reveals for the first time that ATP can enhance LLPS
      most likely by behaving as a bivalent binder. Most importantly, our results imply
      that age-dependent reduction of ATP concentrations may not only result in
      decreasing its capacity in preventing protein aggregation, but also in enhancing
      aggregation.

PMID- 30205961
TI  - Mycobacterium tuberculosis cording in alveolar macrophages of patients with
      pulmonary tuberculosis is likely associated with increased mycobacterial
      virulence.
AB  - Mycobacterium tuberculosis (Mtb) is an infectious agent that causes tuberculosis
      (TB) in humans. A study of the volume of Mtb population and the detection of Mtb
      virulence in the lungs of patients with pulmonary TB are of great importance for
      understanding the infectious process and the outcome of the disease. We analyzed
      the functional state of Mtb and their number in alveolar macrophages obtained
      from the resected lungs of patients with TB in ex vivo culture and determined
      that the number of Mtb, referred mainly to the Beijing genotype family (A0 and
      B0/W148 clusters), were significantly different in cells between different
      patients. Only single Mtb were found in alveolar macrophages of some patients,
      while Mtb were actively replicated in colonies in alveolar macrophages of other
      patients, including cord morphology of Mtb growth (the indicator of Mtb
      virulence). Our data demonstrated association between the formation of Mtb
      cording in alveolar macrophages of patients and increased virulence of Mtb from
      the lungs of these patients in guinea pig TB model. The find of cording formation
      by replicating Mtb in human alveolar macrophages may be used for preliminary
      quick estimation of increased Mtb virulence in individual patients with pulmonary
      TB.

PMID- 30205962
TI  - Single nucleotide polymorphisms of Beijing lineage Mycobacterium tuberculosis
      toxin-antitoxin system genes: Their role in the changes of protein activity and
      evolution.
AB  - The article investigates SNP in genes of toxin-antitoxin systems type II in
      Mycobacterium tuberculosis Beijing lineage strains and their possible role in the
      development and formation of new sublineages. We established the catalog of SNPs
      in 142 TA systems genes in 1349 sequenced genomes of the M. tuberculosis Beijing
      lineage. Based on the catalog, 15 new sublineages were identified as part of
      Beijing lineages by non-synonymous SNP in 21 genes of TA systems. We discovered
      three toxin genes with mutations specific for epidemiologically dangerous
      sublineages Beijing-modern (vapC37 A46G, vapC38 T143C) and Beijing-B0/W148
      (vapC12 A95G). We proved the functional significance of these polymorphisms by
      cloning these genes wild-type and with marker mutations for the Beijing lineage
      vapC12 (A95G), vapC37 (A46G), vapC38 (T143C). In vitro study of their activities
      revealed effect of mutations on the RNase activity of toxin proteins. Mutations
      in vapC37 and vapC38 decreased toxin activity, and mutation in the vapC12
      increased it. We cloned the toxin vapC37 gene of Mycobacterium smegmatis mc2 155
      in both allelic variants: without mutation and with A46G mutation, specific for
      the Beijing-modern lineage. It was shown that this mutation leads to a loss of
      toxicity.

PMID- 30205963
TI  - Diagnostic performance of GM-CSF and IL-2 in response to long-term specific
      antigen cell stimulation in patients with active and latent tuberculosis
      infection.
AB  - BACKGROUND: A simple blood test for detecting active tuberculosis (TB) could be
      key to this epidemic containment, given that a large proportion of patients are
      unable to produce sputum for testing. Currently available interferon-gamma
      release assays (IGRAs) are inadequate to diagnose active TB, with reported pooled
      sensitivity and specificity both under 81%. OBJECTIVE: To explore whether
      cytokines/chemokines other than interferon-gamma in response to long-term cell
      stimulation could improve the ability to distinguish between different TB
      infection status. METHODS: We prospectively enrolled subjects with newly
      diagnosed pulmonary TB and their household contacts in Santiago. All contacts
      were tested with IGRA. Peripheral blood mononuclear cells were obtained and
      antigen-specific stimulated for 72 h before collecting their culture
      supernatants. RESULTS: Subjects with active TB displayed markedly low
      cytokines/chemokines secretion upon PBMC stimulation, with lower GM-CSF being the
      best differentiator from IGRA(+) contacts, with 71% (95% CI 53-85) sensitivity,
      86% (95% CI 65-97) specificity and AUC = 0.79 (p = 0.0003). On the other hand,
      when compared to the uninfected IGRA(-) contacts, higher level of IL-2 secretion
      was the best indicator of active TB, with 73.5% (95% CI 56-87) sensitivity, 85%
      (95% CI 66-96) specificity and AUC = 0.79 (p = 0.0001). No single
      cytokine/chemokine released upon stimulation could accurately differentiate
      between active TB and all TB contacts grouped together. CONCLUSION: GM-CSF and IL
      2 provided the best yield to differentiate active TB from latent TB and from TB
      uninfected, respectively, with higher specificities than that reported for IGRAs.
      However, none of both resulted sensitive enough to be used as a stand-alone
      biomarker for active TB.

PMID- 30205964
TI  - Diagnostic evaluation of an in-house developed single-tube, duplex, nested IS6110
      real-time PCR assay for rapid pulmonary tuberculosis diagnosis.
AB  - OBJECTIVE: To perform a prospective evaluation on the diagnostic performance of
      an in-house developed, duplex nested IS6110 real-time Polymerase-Chain-Reaction
      (PCR) assay (IS6110-qPCR assay) for rapid pulmonary TB diagnosis. METHODS: A
      total of 503 sputum specimens were prospectively collected from July 2016 to
      November 2016. Diagnostic accuracy and optimal cut-off Cycle-threshold (Ct) value
      for IS6110-qPCR assay was determined by Receiver Operating Characteristic (ROC)
      curve. Using the optimal cut-off Ct, diagnostic performance of IS6110-qPCR assay
      was assessed with reference to both bacteriological and clinical information.
      Meanwhile, limit of detection (LOD) was calculated using Mycobacterium
      tuberculosis H37Rv as reference strain. RESULT: ROC curve analysis of IS6110-qPCR
      assay showed a high Area Under the Curve (AUC) value (0.948) with optimal Ct
      value at 24.140. Prospective analysis of IS6110-qPCR assay with cut-off Ct =
      24.140 showed a high overall sensitivity and specificity of 97.2% and 99.7%,
      respectively. No cross reactivity was observed among all non-tuberculous
      mycobacteria specimens in this study. LOD analysis on MTB-spiked sputum showed an
      average detection limit of 5.0 CFU/mL at Ct = 23.18 (+/-SD, 0.57). CONCLUSION:
      IS6110-qPCR assay is a highly accurate and cost-effective assay developed for
      primary screening of suspected TB cases, which is particularly suitable for
      regions with limited resources but high TB burden.

PMID- 30205965
TI  - A genotypic and spatial epidemiologic analysis of Massachusetts' Mycobacterium
      tuberculosis cases from 2012 to 2015.
AB  - BACKGROUND: Massachusetts had a rate of 2.8 cases of tuberculosis (TB) per
      100,000 individuals in 2015. Although TB in Massachusetts is on the decline, the
      case rate remains far above the 2020 National TB Target of 1.4 per 100,000. To
      reduce the TB case rate in Massachusetts, it is necessary to understand the local
      epidemiology and transmission risks. METHODS: We used an existing TB case
      database of Massachusetts TB cases in the time frame from 2012 to 2015, which
      links de-identified patient demographic information with TB genotypes obtained
      from the United States Centers for Disease Control and Prevention's (CDC) TB
      Genotyping Information Management System database. Two or more cases with
      identical genotypes, which were close in space (within 50 km), as determined in a
      geographic information system (GIS), and time (3 years), were considered TB
      clusters. RESULTS: We analyzed 543 genotyped cases. We identified a total of 85
      cases that met the TB cluster criteria, and a total of 33 clusters. US-born
      individuals (p = 0.003), homeless individuals (p = 0.001) and those reporting
      illicit substance use (p = 0.001) and alcohol use (p = 0.001) were more likely to
      appear in a TB cluster. CONCLUSION: Through a combined genotypic and spatial
      epidemiological approach, we identified populations and individuals more likely
      to be in a TB cluster. Testing populations identified as at risk for being in a
      TB cluster, and providing appropriate treatment, may decrease the overall TB case
      rate and support efforts to achieve national 2020 TB targets.

PMID- 30205966
TI  - Generation and application of DNA aptamers against HspX for accurate diagnosis of
      tuberculous meningitis.
AB  - Tuberculous meningitis (TBM) is the most severe manifestation of tuberculosis and
      its diagnosis remains a challenge even today due to the lack of an adequate test.
      HspX antigen of Mycobacterium tuberculosis was previously established as a
      reliable diagnostic biomarker for TBM in an ELISA test format using anti-HspX
      polyclonal antibodies. Towards overcoming the limitations of batch-to-batch
      variation and challenges of scalability in antibody generation, we utilized
      Systematic Evolution of Ligands by EXponential enrichment (SELEX) to develop high
      affinity DNA aptamers against HspX as an alternative diagnostic reagent. Post
      SELEX optimization of the best-performing aptamer candidate, H63, established its
      derivative H63 SL-2 M6 to be superior to its parent. Aptamer H63 SL-2 M6
      displayed a specific and high affinity interaction with HspX (Kd ~9.0 * 10-8 M).
      In an Aptamer Linked Immobilized Sorbent Assay (ALISA), H63 SL-2 M6 significantly
      differentiated between cerebrospinal fluid specimens from TBM and non-TBM
      subjects (n = 87, ***p < 0.0001) with ~100% sensitivity and ~91% specificity.
      Notably, ALISA exhibited comparable performance with previously reported antibody
      based ELISA and qPCR. Altogether, our findings establish the utility of HspX
      aptamer for the reliable diagnosis of TBM and pave the way for developing an
      aptamer-based point-of-care test for TBM.

PMID- 30205967
TI  - IMB-SD62, a triazolothiadiazoles derivative with promising action against
      tuberculosis.
AB  - One lead 3,6-disubstituted 1,2,4-triazolo[3,4-b][1,3,4]thiadiazole was identified
      as an inhibitor of shikimate dehydrogenase with antitubercular activity.
      Following up this compound, we optimized the lead through systematic modification
      of the 3 and 6 positions. The antitubercular activities in vitro, shikimate
      dehydrogenase inhibitory activities and cytotoxicity of derivatives were
      determined. We found IMB-SD62 with lower cytotoxicity and better activity. Thus,
      we studied the in vivo efficacy of IMB-SD62 against Mycobacterium tuberculosis
      and pharmacokinetics of IMB-SD62. In vivo acute M. tuberculosis H37Rv infection
      assay, IMB-SD62 showed antitubercular activity with the mean lung CFU counts
      decreasing 1.7 lg. The plasma pharmacokinetics study in rats showed that the oral
      bioavailability of IMB-SD62 was 14% and the half time was 1.05 h. The results of
      tissue distribution indicated that IMB-SD62 was mainly absorbed by liver and
      lung. In vitro metabolism study suggested that the metabolic ways of IMB-SD62
      were dealkylated, oxidized and demethylated. CYP enzyme inhibition of IMB-SD62 in
      human liver microsomes was also evaluated. IMB-SD62 showed barely inhibition on
      CYP3A4 and CYP2D6. The excretion study manifested that IMB-SD62 was mainly
      eliminated by fecal excretion in rats. We concluded that based on these
      pharmaceutical properties, IMB-SD62 has the potential to be developed into new TB
      drug.

PMID- 30205968
TI  - Human tuberculosis brain promotes neuronal apoptosis but not in astrocytes with
      high expression of vascular endothelial growth factor.
AB  - The present study aimed to investigate the involvement of the angiogenic marker
      vascular endothelia growth factor (VEGF) and apoptotic markers of Bcl-2 and Bax
      in the neurons and astrocytes in the brain infected by Mycobacterium
      tuberculosis. The immunohistochemistry staining was performed to analyze the
      expression of the VEGF, Bcl-2 and Bax in the astrocytes and neurons. The
      expression of VEGF was high in neurons and astrocytes in both the infected brain
      and control tissues with no difference of angiogenic activity (p = 0.40). Higher
      Bcl-2 expression was seen in astrocytes of infected brain tissues compared to the
      control tissues (p = 0.004) promoted a higher anti-apoptotic activity in
      astrocytes. The neurons expressed strong Bax expression in the infected brain
      tissues compared to the control tissues (p < 0.001), which indicated more
      apoptosis in neurons. Thus, neuronal death and survival of infected astrocytes
      together with high expression of VEGF might be associated with formation of brain
      tuberculosis. In conclusion, neurons could be more vulnerable than astrocytes in
      human tuberculosis brain with high expression of VEGF.

PMID- 30205971
TI  - A katG S315T or an ahpC promoter mutation mediate Mycobacterium tuberculosis
      resistance to 2-thiophen carboxylic acid hydrazide, an inhibitor resembling the
      anti-tubercular drugs Isoniazid and Ethionamide.
AB  - Clinical isolates of Mycobacterium tuberculosis and Mycobacterium bovis are
      differentially susceptible to 2-Thiophen Hydrazide (TCH); however its mechanism
      of action or the reasons for that difference are unknown. We report herein that
      under our experimental conditions, TCH inhibits M. tuberculosis in solid but not
      in liquid medium, and that in spite of resembling Isoniazid and Ethionamide, it
      does not affect mycolic acid synthesis. To understand the mechanisms of action of
      TCH we isolated M. tuberculosis TCH resistant mutants which fell into two groups;
      one resistant to TCH and Isoniazid but not to Ethionamide or Triclosan, and the
      other resistant only to TCH with no, or marginal, cross resistance to Isoniazid.
      A S315T katG mutation conferred resistance to TCH while katG expression from a
      plasmid reduced M. tuberculosis MIC to this drug, suggesting a possible
      involvement of KatG in TCH activation. Whole genome sequencing of mutants from
      this second group revealed a single mutation in the alkylhydroperoxide reductase
      ahpC promoter locus in half of the mutants, while the remaining contained
      mutations in dispensable genes. This is the first report of the genetics
      underlying the action of TCH and of the involvement of ahpC as the sole basis for
      resistance to an anti-tubercular compound.

PMID- 30205970
TI  - Novel MprA binding motifs in the phoP regulatory region in Mycobacterium
      tuberculosis.
AB  - MprAB and PhoPR are important two-component systems (TCSs) in Mycobacterium
      tuberculosis, and both regulate EspR, a key regulator of the ESX-1 secretion
      system. Although previous studies suggest that the response regulator PhoP does
      not directly regulate mprA, the interplay between MprAB and PhoPR remains
      unclear. In this study, we found that the response regulator MprA can bind to the
      phoP promoter. Four repeat motifs, D1-D4, constituting two predicted binding
      sites, were located in the region protected by MprA in DNA footprinting. D1-D4
      lack the reported conserved MprA binding sequences, indicating that MprA can
      recognize a greater range of target sites. Interestingly, D1-D2 overlap a
      previously reported PhoP binding site, and mutation of D1-D2 inhibited PhoP
      binding, whereas the D3-D4 site, but not the D1-D2 site, was required for MprA
      binding. EMSA assays also suggest that MprA and PhoP compete to bind to the phoP
      promoter. The results of the transcriptional and western blot assays are
      consistent with a model in which MprA positively controls the phoP expression,
      which in turn upregulates the expression of espR. These findings reveal complex
      regulation of a major mycobacterial TCS by dual TCSs.

PMID- 30205973
TI  - In silico designing of domain B selective gyrase inhibitors for effective
      treatment of resistant tuberculosis.
AB  - One of the major mechanisms followed by the therapeutic agents to target the
      causative organism of TB, Mycobacterium tuberculosis, involves disruption of its
      DNA replication cycle. The process of replication involves two steps, i.e.,
      breakage and reunion of DNA at gyrase A (GyrA) domain and ATP hydrolysis at
      gyrase B (GyrB) domain, both occur simultaneously. Current therapy for multi-drug
      resistant TB (MDR-TB) involves FDA approved, fluoroquinolone-based antibiotics,
      which act by targeting replication process at GyrA domain. However, resistance
      against fluoroquinolones due to mutations in the GyrA domain has limited the use
      of this therapy and shifted the focus of research community on GyrB domain. Thus,
      in the present study novel chemotherapeutic agents for resistant TB were designed
      by exploring GyrB domain using in silico techniques. Pharmacophore model of GyrB
      domain was employed for screening an In-house database. Followed by cross
      screening via a qualitative Hip-Hop pharmacophore model for GyrA to remove non
      selective gyrase B inhibitors. Further molecular dynamics simulations and MM-GBSA
      calculations were performed to determine stability and binding affinity of the
      screened molecules. These analyses resulted in five putative oxindole based
      selective GyrB domain inhibitors, which were synthesized and evaluated for anti
      tubercular activity against M. tuberculosis H37Rv strain. Two compounds exhibited
      significant anti-TB activity, whereas other three compounds were found to be
      outliers of the in silico study.

PMID- 30205972
TI  - Centrifugation and decontamination procedures selectively impair recovery of
      important populations in Mycobacterium smegmatis.
AB  - Diagnosis and treatment monitoring of patients with tuberculosis (TB) requires
      detection of all viable mycobacteria in clinical samples. Quantitation of
      Mycobacterium tuberculosis (Mtb) in sputum is commonly performed by culture after
      sample decontamination to prevent overgrowth by contaminant organisms.
      Exponentially growing cultures have cells that predominately lack non-polar lipid
      bodies whereas stationary cultures have a predominance of cells with non-polar
      lipid bodies. This may reflect rapidly growing 'active' and non-replicating
      'persister' sub-populations respectively in sputum from TB patients. We
      investigated the effect of decontamination on culture-based quantitation of
      exponential and stationary phase cultures of Mycobacterium smegmatis in an
      artificial sputum model. Exponentially growing populations were between 89 and 50
      times more susceptible to decontamination than stationary phase cultures when
      quantified by most probable number and colony forming units. These findings
      suggest that decontamination selectively eliminates the 'active' population. This
      may impair diagnostic sensitivity, treatment monitoring, and compromise clinical
      trials designed to identify new antibiotic combinations with activity against all
      mycobacterial cell states.

PMID- 30205969
TI  - Application of multiplexed ion mobility spectrometry towards the identification
      of host protein signatures of treatment effect in pulmonary tuberculosis.
AB  - RATIONALE: The monitoring of TB treatments in clinical practice and clinical
      trials relies on traditional sputum-based culture status indicators at specific
      time points. Accurate, predictive, blood-based protein markers would provide a
      simpler and more informative view of patient health and response to treatment.
      OBJECTIVE: We utilized sensitive, high throughput multiplexed ion mobility-mass
      spectrometry (IM-MS) to characterize the serum proteome of TB patients at the
      start of and at 8 weeks of rifamycin-based treatment. We sought to identify
      treatment specific signatures within patients as well as correlate the proteome
      signatures to various clinical markers of treatment efficacy. METHODS: Serum
      samples were collected from 289 subjects enrolled in CDC TB Trials Consortium
      Study 29 at time of enrollment and at the end of the intensive phase (after 40
      doses of TB treatment). Serum proteins were immunoaffinity-depleted of high
      abundant components, digested to peptides and analyzed for data acquisition
      utilizing a unique liquid chromatography IM-MS platform (LC-IM-MS). Linear mixed
      models were utilized to identify serum protein changes in the host response to
      antibiotic treatment as well as correlations with culture status end points.
      RESULTS: A total of 10,137 peptides corresponding to 872 proteins were
      identified, quantified, and used for statistical analysis across the longitudinal
      patient cohort. In response to TB treatment, 244 proteins were significantly
      altered. Pathway/network comparisons helped visualize the interconnected
      proteins, identifying up regulated (lipid transport, coagulation cascade,
      endopeptidase activity) and down regulated (acute phase) processes and pathways
      in addition to other cross regulated networks (inflammation, cell adhesion,
      extracellular matrix). Detection of possible lung injury serum proteins such as
      HPSE, significantly downregulated upon treatment. Analyses of microbiologic data
      over time identified a core set of serum proteins (TTHY, AFAM, CRP, RET4, SAA1,
      PGRP2) which change in response to treatment and also strongly correlate with
      culture status. A similar set of proteins at baseline were found to be predictive
      of week 6 and 8 culture status. CONCLUSION: A comprehensive host serum protein
      dataset reflective of TB treatment effect is defined. A repeating set of serum
      proteins (TTHY, AFAM, CRP, RET4, SAA1, PGRP2, among others) were found to change
      significantly in response to treatment, to strongly correlate with culture
      status, and at baseline to be predictive of future culture conversion. If
      validated in cohorts with long term follow-up to capture failure and relapse of
      TB, these protein markers could be developed for monitoring of treatment in
      clinical trials and in patient care.

PMID- 30205974
TI  - Genetic diversity of Mycobacterium tuberculosis complex isolates circulating in
      an area with high tuberculosis incidence: Using 24-locus MIRU-VNTR method.
AB  - We aimed to determine the genetic diversity, phylogenetic relationship and
      transmission dynamics of Mycobacterium tuberculosis complex (MTBC) genotypes in
      an area with high tuberculosis (TB) incidence. A set of 164 MTBC isolates from
      new TB patients of Golestan province, Iran, were subjected to genotyping using
      the standard 24-locus MIRU-VNTR method. Recent TB transmission was evaluated and
      phylogenetic relationships were analysed by minimum spanning tree and cluster
      graph methods. Among the 164 isolates, 132 distinct patterns were detected. The
      48 clustered isolates (29.3%) were distributed into 16 clusters ranging in size
      from 2 to 12 isolates. The most frequent genotype was Central Asian Strain/Delhi
      (CAS/Delhi) (n = 67, 40.8%), followed by NEW-1 (n = 53, 32.3%) and Beijing (n =
      19, 11.6%) genotypes. Thirty five (72.9%) of NEW-1 isolates were recovered from
      immigrant patients and 84.2% (n = 16) of Beijing genotypes recovered from native
      cases. Statistically significant association was found between clustering and
      smoking (p = 0.047), drug addiction (p = 0.01) and prison history (p = 0.003).
      The estimated proportion of recent transmission was 19.5%. Presence of highly
      diverse MTBC isolates circulating in this province without a dominant genotype
      might be a consequence of importation of various genotypes in this area.

PMID- 30205976
TI  - Combined effects of aging and obesity on postural control, muscle activity and
      maximal voluntary force of muscles mobilizing ankle joint.
AB  - OBJECTIVE: The aim of the study was to investigate the influence of age and/or
      obesity on postural control, ankle muscle activities during balance testing and
      force production capacities. MATERIALS AND METHODS: 4 groups; control group (CG;
      n = 25; age = 31.8 +/- 7.5 years; BMI = 21.4 +/- 2.5 kg/m2), obese group (OG; n =
      25; age = 34.4 +/- 9.5 years; BMI = 39.6 +/- 5.4 kg/m2), elderly group (EG; n =
      15; age = 77.1 +/- 8.4 years; BMI = 24.4 +/- 1.3 kg/m2) and obese elderly group
      (ObEG; n = 12; age = 78.6 +/- 6.6 years; BMI = 34.5 +/- 3.1 kg/m2) performed
      maximal voluntary contraction (MVC) before testing to calculate the maximal
      relative force of ankle plantar flexor (PF) and dorsal flexor (DF) muscles.
      Center of pressure (CoP) parameters and the electromyography (EMG) activity of PF
      and DF muscles were collected during MVC, quiet standing and limit of stability
      (LoS) testing along antero-posterior and medio-lateral axes. RESULTS: Maximal
      relative force was higher in EG and ObEG than CG and OG, respectively (p <
      0.001). CoP parameters, distance traveled along the antero-posterior axis and EMG
      activity of PF were higher in OG, EG and ObEG compared to CG (p < 0.001) and in
      EG compared to ObEG (p < 0.05).The EMG activity of PF was positively correlated
      with CoP parameters in OG and ObEG (r > 0.6; p < 0.05). Maximal relative force of
      PF (r > -0.6; p < 0.05) was negatively correlated with CoP parameters in ObEG and
      EG. CONCLUSION: Obesity-related postural control alteration is associated with
      increased activity of PF. This neuromuscular adaptation may reflect
      deteriorations of the proprioceptive system and is likely additional to age
      related muscular impairments. This may be a mechanism by which obesity increases
      postural control alterations in elderly.

PMID- 30205975
TI  - The EU approved antimalarial pyronaridine shows antitubercular activity and
      synergy with rifampicin, targeting RNA polymerase.
AB  - The search for compounds with biological activity for many diseases is turning
      increasingly to drug repurposing. In this study, we have focused on the European
      Union-approved antimalarial pyronaridine which was found to have in vitro
      activity against Mycobacterium tuberculosis (MIC 5 MUg/mL). In macromolecular
      synthesis assays, pyronaridine resulted in a severe decrease in incorporation of
      14C-uracil and 14C-leucine similar to the effect of rifampicin, a known inhibitor
      of M. tuberculosis RNA polymerase. Surprisingly, the co-administration of
      pyronaridine (2.5 MUg/ml) and rifampicin resulted in in vitro synergy with an MIC
      0.0019-0.0009 MUg/mL. This was mirrored in a THP-1 macrophage infection model,
      with a 16-fold MIC reduction for rifampicin when the two compounds were co
      administered versus rifampicin alone. Docking pyronaridine in M. tuberculosis RNA
      polymerase suggested the potential for it to bind outside of the RNA polymerase
      rifampicin binding pocket. Pyronaridine was also found to have activity against a
      M. tuberculosis clinical isolate resistant to rifampicin, and when combined with
      rifampicin (10% MIC) was able to inhibit M. tuberculosis RNA polymerase in vitro.
      All these findings, and in particular the synergistic behavior with the
      antitubercular rifampicin, inhibition of RNA polymerase in combination in vitro
      and its current use as a treatment for malaria, may suggest that pyronaridine
      could also be used as an adjunct for treatment against M. tuberculosis infection.
      Future studies will test potential for in vivo synergy, clinical utility and
      attempt to develop pyronaridine analogs with improved potency against M.
      tuberculosis RNA polymerase when combined with rifampicin.

PMID- 30205978
TI  - Normal force distribution and posture of a hand pressing on a flat surface.
AB  - Hand strength data are needed to understand and predict hand postures and finger
      loads while placing the hand on an object or surface. This study aims to analyze
      the effect of hand posture and surface orientation on hand force while pressing a
      flat surface. Twelve participants, 6 females and 6 males ages 19-25, performed
      three exertions (100%, 30% and 10% MVC- Maximum Voluntary Contraction)
      perpendicular to a plate in 4 angles (-45 degrees , 0 degrees , 45 degrees  and
      90 degrees  with respect to the horizontal plane) at elbow height. Exertions
      involved pushing in two postures: (1) whole hand and (2) constrained to only
      using the fingertips. Inter-digit joint angles were recorded to map hand and
      finger motions and estimate joint moments for each condition. Participants
      exerted twice the force when pushing with whole hand vs. fingertips. 72-75% of
      the total force was exerted over the base of the palm, while only 11-13% with the
      thumb for exertions at 90 degrees , 45 degrees  or 0 degrees  plate angles. Males
      maximum force for pushing at 0 degrees , 45 degrees  and 90 degrees  plates
      averaged 49% higher than females for the whole hand and 62% for the fingertips (p
      < 0.01). There was no significant sex difference (p > 0.05) for the -45 degrees 
      plate. Thumb joint loads were generally higher than the other individual fingers
      (p < 0.05) in all % MVC and accounted for 12% of total force during whole hand
      exertions. On average, joint moments were 30% higher during fingertip conditions
      vs. whole hand. Thumb and finger joint moment magnitudes when pushing the plate
      at 100% MVC indicated that Metacarpophalangeal (MCP) joint moments were higher (p
      < 0.05) than Distal Interphalangeal joints (DIP) and Proximal Interphalangeal
      joints (PIP) under whole hand and fingertips conditions.

PMID- 30205977
TI  - Structural role of osteocalcin and osteopontin in energy dissipation in bone.
AB  - Non-collagenous proteins are a vital component of bone matrix. Amongst them,
      osteocalcin (OC) and osteopontin (OPN) hold special significance due to their
      intimate interaction with the mineral and collagenous matrix in bone. Both
      proteins have been associated with microdamage and fracture, but their structural
      role in energy dissipation is unclear. This study used bone tissue from genetic
      deficient mice lacking OC and/or OPN and subjected them to a series of creep
      fatigue-creep tests. To this end, whole tibiae were loaded in four-point bending
      to 70% stiffness loss which captured the three characteristic phases of fatigue
      associated with initiation, propagation, and coalescence of microdamage. Fatigue
      loading preceded and followed creep tests to determine creep and dampening
      parameters. Microdamage in the form of linear microcracks and diffuse damage were
      analyzed by histology. It was shown that OC and OPN were 'activated' following
      stiffness loss associated with fatigue damage where they facilitated creep and
      dampening parameters (i.e. increased energy dissipation). More specifically, post
      fatigue creep rate and dampening were significantly greater in wild-types (WTs)
      than genetic deficient mice (p < 0.05). These results were supported by
      microdamage analysis which showed significant increase in creep-associated
      diffuse damage formation in WTs compared to genetic deficient groups (p < 0.05).
      Based on these findings, we propose that during local yield events, OC and OPN
      rely on ionic interactions of their charged side chains and on hydrogen bonding
      to dissipate energy in bone.

PMID- 30205979
TI  - Transcriptome profiling in blood before and after hepatitis B vaccination shows
      significant differences in gene expression between responders and non-responders.
AB  - INTRODUCTION: As the hepatitis B virus is widely spread and responsible for
      considerable morbidity and mortality, WHO recommends vaccination from infancy to
      reduce acute infection and chronic carriers. However, current subunit vaccines
      are not 100% efficacious and leave 5-10% of recipients unprotected. METHODS: To
      evaluate immune responses after Engerix-B vaccination, we determined, using mRNA
      sequencing, whole blood early gene expression signatures before, at day 3 and day
      7 after the first dose and correlated this with the resulting antibody titer
      after two vaccine doses. RESULTS: Our results indicate that immune related genes
      are differentially expressed in responders mostly at day 3 and in non-responders
      mostly at day 7. The most remarkable difference between responders and non
      responders were the differentially expressed genes before vaccination. The
      granulin precursor gene (GRN) was significantly downregulated in responders while
      upregulated in non-responders at day 0. Furthermore, absolute granulocytes
      numbers were significantly higher in non-responders at day 0. CONCLUSION: The non
      responders already showed an activated state of the immune system before
      vaccination. Furthermore, after vaccination, they exhibited a delayed and partial
      immune response in comparison to the responders. Our data may indicate that the
      baseline and untriggered immune system can influence the response upon hepatitis
      B vaccination.

PMID- 30205980
TI  - Near-infrared spectroscopic imaging of the whole hand: A new tool to assess
      tissue perfusion and peripheral microcirculation in scleroderma.
AB  - OBJECTIVES: Systemic sclerosis (SSc) causes functional and structural
      microcirculatory dysfunction, affecting also distal extremities. Optical Near
      InfraRed Spectroscopy (NIRS) of blood HbO2 saturation (stO2) is able to evaluate
      O2 delivery/consumption balance in the explored tissue. The NIRS-sensitive camera
      non-invasively detects stO2 values in superficial tissues, automatically
      generating 2D-imaging maps in real time. We aimed at testing whether NIRS hand
      imaging may evaluate peripheral microcirculatory dysfunction and its spatial
      heterogeneity in SSc patients compared to controls. METHODS: Forty SSc patients
      (aged 55.1 +/- 15.6 years) and twenty-one healthy controls (aged 54.3 +/- 14.5
      years, p = 0.89) were studied by palmar hand NIRS-2D imaging. A blood pressure
      cuff was applied to the forearm and 3 min ischemia was induced. Images were
      acquired at basal conditions and every 10 seconds during 3 minutes of ischemia
      and 5 minutes of reperfusion. Five regions of interest were positioned on each
      fingertip, from the second to the fifth finger and one on the thenar eminence.
      RESULTS: A significant difference was found between controls and SSc patients in
      basal stO2 (84.3 +/- 7.5 vs. 75.4 +/- 10.9%, p < 0.001), minimum stO2 (65.2 +/-
      8.0 vs. 53.4 +/- 10.1%, p < 0.001) and time to maximum stO2 during hyperemia (63
      +/- 38 vs. 85 +/- 49 s, p < 0.05). Among clinical characteristics, anti-Scl70
      antibody positivity, digital ulcers history and smoke exposure affected NIRS
      parameters, as well as sildenafil and statins therapy. Conversely, no significant
      differences were found in NIRS-2D values between different nailfold
      videocapillaroscopy patterns. CONCLUSION: NIRS-2D imaging is a simple, automated
      tool to non-invasively detect regional microcirculatory impairment in SSc, which
      seems to add significant functional information to the morphological picture of
      nailfold-videocapillaroscopy.

PMID- 30205981
TI  - Exploring the patient experience of digital ulcers in systemic sclerosis.
AB  - Digital ulcers are common in patients with systemic sclerosis, affecting over
      half of patients during the course of their disease. For some patients, digital
      ulcers occur as isolated phenomena; whereas, for others, digital ulceration is
      recurrent, and often refractory to intervention. Demonstrating treatment efficacy
      for digital ulcer disease has typically focussed on clinician opinion of ulcer
      healing and new ulcer occurrence. Advances in management have improved outcomes
      which may have had the unfortunate effect of rendering traditional trial
      endpoints less effective at demonstrating treatment efficacy. Despite recent
      improvements in management, our work is not complete and digital ulceration
      remains a major cause of morbidity for many patients with systemic sclerosis.
      This review shall examine the patient experience of digital ulcers in systemic
      sclerosis. We shall consider how a detailed understanding of the severity and
      burden of digital ulceration, aetiopathogenesis, and their impact on emotional
      health, function, work and social participation might inform the development of
      novel clinical trial outcomes that can support future advances in the assessment
      and management of digital ulceration in systemic sclerosis.

PMID- 30205982
TI  - Racial/ethnic variation in stroke rates and risks among patients with systemic
      lupus erythematosus.
AB  - OBJECTIVE: Systemic lupus erythematosus (SLE), which is associated with increased
      stroke risk, is more prevalent and often more severe among Blacks, Asians, and
      Hispanics than Whites. We examined racial/ethnic variation in stroke rates and
      risks, overall and by hemorrhagic versus ischemic subtype, among SLE patients.
      METHODS: Within Medicaid (2000-2010), we identified patients aged 18-65 with SLE
      (>= 3 ICD-9 710.0 codes, >= 30 days apart) and >=12 months of continuous
      enrollment. Subjects were followed from index date to first stroke event, death,
      disenrollment, or end of follow-up. Race/ethnicity-specific annual event rates
      were calculated for stroke overall and by subtypes (hemorrhagic vs. ischemic). We
      used Cox proportional hazard models to estimate hazard ratios (HR) of stroke by
      race/ethnicity, adjusting for comorbidities and the competing risk of death.
      RESULTS: Of 65,788 SLE patients, 93.1% were female. Racial/ethnic breakdown was
      42% Black, 38% White, 16% Hispanic, 3% Asian, and 1% American Indian/Alaska
      Natives. Mean follow-up was 3.7 +/- 3.0 years. After multivariable adjustment,
      Blacks were at increased risk of overall stroke (HR 1.34 [95%CI 1.18-1.53),
      hemorrhagic stroke (HR 1.42 [1.00-2.01]), and ischemic stroke (HR 1.33 [1.15
      1.52]) compared to Whites. Hispanics were at increased risk of overall stroke (HR
      1.25 [1.06-1.47)] and hemorrhagic stroke (HR 1.79 [95% CI 1.22-2.61]), but not
      ischemic stroke, compared to Whites. CONCLUSION: Among SLE patients enrolled in
      Medicaid, we observed elevated stroke risk (overall and by subtype) among Blacks
      and Hispanics compared to Whites, suggesting the importance of early recognition
      and screening for stroke risk factors among Blacks and Hispanics.

PMID- 30205983
TI  - Treat to target strategy in early rheumatoid arthritis versus routine care - A
      comparative clinical practice study.
AB  - OBJECTIVE: To assess the 2-year effect on disease activity and health-related
      quality of life (HRQoL) of implementing a clinical practice treat-to-target (T2T)
      strategy in patients with rheumatoid arthritis (RA). METHODS: Patients in the
      Norwegian Very Early Arthritis Cohort 2.0 (NOR-VEAC 2.0), included 2010-2015,
      were treated according to T2T principles with visits at baseline, 3, 6, 9, 12
      months, then every 6 months plus monthly visits until DAS28 <2.6. These patients
      were compared to a pre-T2T cohort of patients included in the Norwegian Disease
      Modifying Anti-Rheumatic Drug (NOR-DMARD) register 2006-2009. Both groups had a
      clinical diagnosis of RA (<=1 year) and were DMARD naive. Disease activity and
      HRQoL outcomes were analysed, and the primary outcome was SDAI remission (<=3.3)
      at 2 years. RESULTS: The T2T cohort included 293 patients (mean (SD) age 54 (13)
      years, 66% females, disease duration median (25,75 perc) 98 (57,164) days) and
      the routine care cohort 392 patients (age 54 (13) years, 68% females, 4 (0,30)
      days since diagnosis). At 2 years, the proportion of patients achieving SDAI
      remission was 46% in the T2T cohort compared to 31% in the routine care cohort.
      EQ-5D was similar at baseline, but differed significantly between groups at 2
      years (median (25,75 perc) 0.77 (0.69, 0.85) vs 0.73 (0.59, 0.80), p < 0.001).
      Methotrexate monotherapy was the dominant DMARD regimen used to achieve SDAI
      remission in both cohorts. CONCLUSION: Higher remission rates and better HRQoL
      were achieved in patients following a T2T strategy in clinical practice compared
      to routine care.

PMID- 30205984
TI  - Osteoporosis Self-Assessment Tool As a Screening Tool for Predicting Osteoporosis
      in Elderly Chinese Patients With Established Rheumatoid Arthritis.
AB  - Osteoporosis Self-Assessment Tool for Asians (OSTA) is an indicator for assessing
      osteoporosis in postmenopausal women. The aim of this study was to investigate
      the value of OSTA index on predicting osteoporosis in elderly Chinese patients
      with established rheumatoid arthritis (RA). A total of 320 patients with RA and
      158 normal individuals were recruited from January 2015 to October 2017. Bone
      mineral density (BMD) at the femur and lumbar spine was measured by dual-energy X
      ray absorptiometry. RA group and control group were divided into low risk
      (values>=-1), medium risk (values between -4 and -1), and high risk (values <=-4)
      group according to the value of OSTA index. One-way analysis of variance showed
      that BMD at all detected regions among the 3 groups were obviously different (p <
      0.0001). Incidences of osteoporosis among different OSTA groups were 21.76%
      (47/216), 56.41% (44/78), and 80.77% (21/26), separately (x2 = 67.389, p <
      0.0001). In RA group including premenspausal or postmenspausal female subgroup,
      prevalences of osteoporosis among different OSTA groups were different (p < 0.05
      0.0001). We also found a positive linear correlation between OSTA index and BMD
      (p < 0.0001) both in RA and in control groups. Logistic regression revealed OSTA
      index (odds ratio = 0.734, p < 0.0001, 95% confidence interval: 0.657-0.819) was
      a protective factor for occurrence of RA-induced osteoporosis. OSTA had the
      highest discriminatory power, with an estimated Area Under Curve (AUC) of 0.750
      (95% confidence interval 0.694-0.807, p < 0.0001), sensitivity of 76.9% and
      specificity of 66.5%. Our findings indicated that OSTA index was closely
      associated with BMD in RA patients, the degree of correlation was much stronger
      than age or BMI. OSTA index was a predictor for osteoporosis in RA, but it might
      have little relationship with disease status in RA.

PMID- 30205985
TI  - Ageing Effects on 3-Dimensional Femoral Neck Cross-Sectional Asymmetry:
      Implications for Age-Related Bone Fragility in Falling.
AB  - This paper explores the effects of aging on femoral neck (FN) anatomy in a study
      of women aged 20-90 years in relation to implications for FN fracture propensity
      in buckling. Five hundred and four participants were scanned by Quantitative
      Computed Tomography and analyzed using Quantitative Computed Tomography Pro BIT
      (Mindways). FN cross-section was split through geometric center into superior and
      inferior sectors. Bone mass, structural measurements, and bone mineral density
      were analyzed. Buckling ratio was calculated as ratio of buckling radius to
      cortical thickness. Between 2nd decade and 8th decade, age-related integral bone
      mass reduction in superior sector was substantially larger than in inferior
      sector (33% compared to 21%), especially in cortical bone superiorly compared to
      inferiorly (53% vs 21%; p < 0.001), principally due to reduction in cortical
      thickness, averaged cortical thickness (56%) with little difference in density.
      Superior and inferior sector trabecular bone mineral density reduction was
      similar at 41% and 43% respectively. Differential cortical bone loss in superior
      sector resulted in a 59% inferior displacement (delta) of center-of-mass from
      geometric center. Differences in delta and averaged cortical thickness with age
      accounted for a 151% increase in mean superior buckling ratio from 9 to 23.
      Analysis confirms significant progressive age-related superior cortical bone loss
      as the major age effect on FN structure with relative preservation of inferior
      cortex probably related to maintenance of inferior sector by regular loading as a
      result of standing and walking. Computation of buckling ratio may allow
      prediction of fracture propensity in a sideways fall.

PMID- 30205986
TI  - Does the Antitumor Necrosis Factor-alpha Therapy Decrease the Vertebral Fractures
      Occurrence in Inflammatory Bowel Disease?
AB  - BACKGROUND/OBJECTIVE: Osteoporosis and osteoporotic fracture risk are
      extraintestinal manifestations of the inflammatory bowel disease, whose
      etiopathogenic mechanisms have not been determined yet. Anti-tumor necrosis
      factor (TNF)-alpha are used in treatment of inflammatory bowel disease (IBD), but
      it is unknown if they play a role in osteoporotic fracture prevention. The
      objective of this study was to know if anti-TNF decreases fracture risk or
      modifies bone mineral density. To determine the possible risk factors associated
      with fractures, and assess the incidence of vertebral fractures in IBD patients.
      METHODS: Longitudinal prospective cohort study (7 yr of follow-up); which
      included 71 IBD patients, 23 received anti-TNF-alpha; the remaining 48 received
      conventional treatment, constituted the control group. Patients participated in a
      questionnaire which gathered risk factors associated with the development of
      osteoporosis and fractures. Radiographs of the dorsolumbar-spine were performed
      and also a bone density measurement. Their biochemical and bone remodeling
      parameters were determined. RESULTS: Although patients who did not receive anti
      TNF-alpha, suffered more fractures but biologic therapy did not reduce the risk
      of new vertebral fractures. The increase of bone mass was significantly higher
      the group treated with anti-TNF-alpha. The increase in the lumbar spine was of 8%
      and in the femoral neck was of 6.7%. The only determinant factor for the
      incidence of vertebral fractures was a history of previous fractures (odds ratio
      of 12.8; confidence interval 95% 2.37-69.9; p = 0.003). The incidence of
      vertebral fractures in IBD patients was considerably high: 26.7/700 patient-yr.
      CONCLUSIONS: Anti-TNF-alpha, although increased bone mass in these patients, did
      not reduce the risk of new vertebral fractures. In this study, patients with IBD
      have a considerably high incidence of fractures. Only the existence of previous
      vertebral fractures was a predictive factor for consistent fractures.

PMID- 30205987
TI  - Health Care Resource Utilization Among Children With Congenital Heart Disease: A
      Population-Based Study.
AB  - BACKGROUND: Data regarding health care resource utilization (HRU) in early
      childhood among children with congenital heart disease (CHD) are scarce.
      Therefore, we sought to describe the extent of HRU incurred among children with
      CHD in the first 5 years of life. METHODS: This population-based retrospective
      cohort study included all children born between January 2005 and March 2014 in
      Alberta, Canada. We linked inpatient, outpatient, practitioner claims, and drug
      dispensing databases with vital statistics (birth and death registries). RESULTS:
      In the first year of life, the cumulative hospitalization rate per 100 children
      was 335 (95% confidence interval: 312-360) for single ventricle (SV) children,
      200 (194-206) for moderate-complex CHD, and 152 (149-156) for simple CHD vs 109
      (108-109) among children without CHD (P < 0.001). The ambulatory-care visit rate
      per 100 children was 4871 (4780-4963) for SV, 2278 (2258-2299) for moderate
      complex, and 1416 (1405-1426) for simple CHD vs 246 (246-247) for children
      without CHD (P < 0.001). The rates of physician claims and drug dispensing also
      demonstrated similar patterns. The median total hospitalization length of stay
      during the first year of life was 54 days (interquartile range: 26-95) in SV, 15
      (4-39) in moderate-complex, and 6 (2-26) in simple CHD compared with 2 (1-3)
      among children without CHD (P < 0.001). These differences remained throughout the
      first 5 years of life, with children with CHD having consistently higher
      hospitalization rates and emergency department visit rates in every year of age
      compared with children without CHD. CONCLUSIONS: Cumulative HRU is high among
      children with CHD in the first 5 years of life and increases with increasing CHD
      severity. Improving survival of SV lesions will require increasing resource
      allocation to this group.

PMID- 30205988
TI  - Right Ventricular Function Evolution With Pregnancy in Repaired Tetralogy of
      Fallot.
AB  - This case illustrates the evolution of right ventricular (RV) 3-dimensional (3D)
      area strain during pregnancy in a patient with repaired Tetralogy of Fallot. The
      report highlights impairment in RV function with pregnancy, suggesting the
      importance of prepregnancy RV systolic function assessment, especially using 3D
      echocardiography.

PMID- 30205989
TI  - Anabolic Androgenic Steroid Use as a Cause of Fulminant Heart Failure.
AB  - A 39-year-old male weightlifter presented in fulminant heart failure. An
      echocardiogram revealed severe global biventricular failure. Left ventricular
      (LV) systolic function was estimated at 15%. His dilated cardiomyopathy was
      attributed to his use of both testosterone and boldenone in the 3-month period
      before his presentation. Although the deleterious effects of androgenic- anabolic
      steroids on diastolic function are well known, the effects of these drugs on
      systolic function is an area of ongoing investigation. Our case suggests that
      androgenic anabolic steroid use should be considered in the differential
      diagnosis of patients presenting with acute heart failure.

PMID- 30205990
TI  - Successful Percutaneous Closure of a Ruptured Saphenous Vein Graft Aneurysm.
AB  - A 68-year-old man with previous coronary artery bypass surgery presented with
      acute onset chest pain. After ruling out an acute coronary syndrome, a computed
      tomography scan demonstrated a giant aneurysm (10 cm * 8 cm) of the right
      coronary artery saphenous vein graft (SVG) with signs of rupture into the
      mediastinum. An Amplatzer Vascular Plug II was successfully deployed at the
      proximal anastomosis of the SVG, achieving complete exclusion. At 6-month follow
      up the patient remained asymptomatic and a computed tomography scan confirmed
      adequate position of the device. Amplatzer Vascular Plug II is a reasonable
      alternative for SVG aneurysm closure, providing the vein graft supplies nonviable
      myocardium.

PMID- 30205991
TI  - Editorial.

PMID- 30205992
TI  - Low-Intensity Pulsed Ultrasound Treatment Accelerates Angiogenesis by Activating
      YAP/TAZ in Human Umbilical Vein Endothelial Cells.
AB  - As a non-invasive method, low-intensity pulsed ultrasound (LIPUS) can accelerate
      fracture healing. The mechanisms responsible for the enhanced fracture healing
      need to be studied further. Activation of YAP/TAZ, key mediators of the Hippo
      signaling pathway, could promote angiogenesis and vascular remodeling. The
      purpose of this study was to determine whether LIPUS treatment can activate
      YAP/TAZ. Human umbilical vein endothelial cells (HUVEC) were used. After LIPUS
      treatment, Western blot and immunofluorescence staining were used for YAP/TAZ
      activation. Small interfering RNA (siRNA) of YAP and short hairpin LATS1/2
      (shLATS1/2) were used to check whether there is cross-talk with the Hippo
      pathway. The phosphorylated YAP (p-127 and p-397) protein increased more than 3
      fold 0.5 h after LIPUS treatment (p < 0.05). TAZ protein increased 3.0-, 2.0- and
      1.5-fold 0.5, 6 and 12 h after LIPUS treatment. We found that LIPUS treatment
      activates YAP/TAZ, which is translocated into the cell nucleus to activate target
      genes. This process can be inactivated by siYAP and activated by shLATS1/2. The
      cross-talk with the Hippo pathway can initiate angiogenesis so as to accelerate
      fracture healing by LIPUS.

PMID- 30205993
TI  - Myocardial Thermal Ablation with a Transesophageal High-Intensity Focused
      Ultrasound Probe: Experiments on Beating Heart Models.
AB  - Described here is a study of transesophageal thermal ablation of isolated and
      perfused beating hearts and non-human primates. An endoscope integrating a
      transesophageal echocardiography probe and a high-intensity focused ultrasound
      transducer was built and tested on five Langendorff-isolated hearts and three 30
      kg baboons. B-Mode ultrasound, passive elastography and magnetic resonance
      imaging were performed to monitor thermal lesions. In isolated hearts, continuous
      and gated sonication parameters were evaluated with acoustic intensities of 9-12
      W/cm2. Sonication parameters of gated exposures with 12 W/cm2 acoustic intensity
      for 5 min consistently produced visible lesions in the ventricles of isolated
      hearts. In animals, left atria and ventricles were exposed to repeated continuous
      sonications (4-15 times for 16 s) at an acoustic intensity at the surface of the
      transducer of 9 W/cm2. Clinical states of the baboons during and after the
      treatment were good. One suspected lesion in the left ventricle could be
      evidenced by elastography, but was not confirmed by magnetic resonance imaging.
      The transesophageal procedure therefore has the potential to create thermal
      lesions in beating hearts and its safety in clinical practice seems promising.
      However, further technical exploration of the energy deposition in the target
      would be necessary before the next pre-clinical experiments.

PMID- 30205994
TI  - Automatic Methods for Carotid Contrast-Enhanced Ultrasound Imaging Quantification
      of Adventitial Vasa Vasorum.
AB  - Adventitial vasa vasorum are physiologic microvessels that nourish artery walls.
      In the presence of cardiovascular risk factors, these microvessels proliferate
      abnormally. Studies have reported that they are the first stage of atheromatous
      disease. Contrast-enhanced ultrasound (CEUS) of the carotid allows direct,
      quantitative and non-invasive visualization of the adventitial vasa vasorum.
      Hence, the development of computer-assisted methods that speed image analysis and
      eliminate user subjectivity is important. We developed methods for automatic
      analyses and quantification of vasa vasorum neovascularization in CEUS and tested
      these methods in a cohort of 186 individuals, 63 of whom were healthy volunteers.
      We implemented alternative automatic strategies for using the images to stratify
      patients according to their risk group and compare the strategies with respect to
      diagnostic performance. An automatic single-parameter strategy performs less
      effectively than the corresponding Arcidiacono method based on manual
      interpretation of the images (68 < area under the receiver operating
      characteristic curve [AUROC] for the manual Arcidiacono method < 82; 60 < AUROC
      for the automatic single-parameter strategy < 63). However, by use of additional
      image parameters, an automatic multiparameter strategy has significantly improved
      performance with respect to the manual Arcidiacono method (78 < AUROC < 90). The
      automatic multiparameter strategy is a valuable alternative to the manual
      Arcidiacono method, improving both diagnostic speed and diagnostic accuracy.

PMID- 30205995
TI  - Edaravone Reduces Iron-Mediated Hydrocephalus and Behavioral Disorder in Rat by
      Activating the Nrf2/HO-1 Pathway.
AB  - Our previous studies have demonstrated that hemorrhage-derived iron has a key
      role in causing brain injury after intraventricular hemorrhage (IVH). Based on
      this finding, we hypothesized that edaravone, a free-radical scavenger, has the
      potential to alleviate hydrocephalus and neurological deficits post-IVH by
      suppressing iron-induced oxidative stress. Thus, this study aimed to investigate
      the efficacy of edaravone for rats with FeCl3 injection, as well as to explore
      the related molecular mechanism. An experimental model was established in adult
      male Sprague-Dawley rats via FeCl3 injection into the right lateral ventricle.
      Edaravone or vehicle was administered immediately, 1 day and 2 days after
      intraventricular injection. Brain water content, magnetic resonance imaging,
      neurological score, oxidative stress assays, Western blot analysis, and electron
      microscopy were employed to evaluate brain injury in these rats. Intraventricular
      injection of FeCl3 induced brain edema, ventricular dilation, and neurobehavioral
      disorder in rats. Edaravone treatment significantly attenuated the above
      symptoms, reduced ependymal cilia and neuron damage, and inhibited oxidative
      stress (elevated levels of an antioxidant, superoxide dismutase; decreased levels
      of an oxidant, malondialdehyde). Moreover, edaravone administration effectively
      activated the Nrf2/HO-1 signaling pathway in rat brain following FeCl3 injection.
      These results showed that edaravone treatment alleviated brain edema, ventricular
      expansion, and neurological disorder after FeCl3 injection. The possible
      mechanism is by protecting ependymal cilia and neurons from oxidative stress
      injury and activating the Nrf2/HO-1 signaling pathway. These results provide
      further experimental evidence for edaravone application in the treatment of IVH.

PMID- 30205996
TI  - Superficial Temporal Artery to Anterior Cerebral Artery Hemi-bonnet Bypass Using
      Radial Artery Graft for Prevention of Complications after Surgical Treatment of
      Partially Thrombosed Large/Giant Anterior Cerebral Artery Aneurysm.
AB  - BACKGROUND: Partially thrombosed large/giant aneurysm of the anterior cerebral
      artery is still challenging because this complex aneurysm requires arterial
      revascularization in the deep operation field. Therefore, direct neck clipping is
      often impossible. We describe our experiences with extracranial-intracranial
      bypass as an insurance bypass prior to clipping of partially thrombosed anterior
      cerebral artery aneurysms, and discuss the microsurgical technique and strategy.
      CLINICAL PRESENTATION: Consecutive, single-surgeon experience with the surgical
      treatment of partially thrombosed anterior cerebral artery aneurysms was
      retrospectively reviewed. Three cases of partially thrombosed anterior cerebral
      artery aneurysms, 2 anterior communicating artery aneurysms, and 1
      postcommunicating artery (A2 segment of the anterior cerebral artery) aneurysm,
      presented as mass effect symptoms from giant aneurysms in 2 patients and
      incidentally discovered aneurysm in one patient. Superficial temporal artery
      radial artery graft-anterior cerebral artery hemi-bonnet bypass was performed as
      an insurance bypass prior to clipping of the partially thrombosed anterior
      cerebral artery aneurysms. Complete aneurysm obliteration and bypass patency were
      demonstrated in all 3 patients. No neurological sequelae occurred. CONCLUSIONS:
      Superficial temporal artery-radial artery graft-anterior cerebral artery hemi
      bonnet bypass prior to aneurysm dissection can avoid ischemic complication during
      temporary occlusion and secures permanent revascularization after complete
      obliteration of partially thrombosed large/giant anterior cerebral artery
      aneurysm.

PMID- 30205998
TI  - Prevalence of Balance Impairment Among Stroke Survivors Undergoing
      Neurorehabilitation in Nigeria.
AB  - BACKGROUND: Poststroke balance impairment adversely affects stroke outcomes and
      addressing the impairment is expected to constitute an important focus of
      neurorehabilitation. AIMS: To examine the prevalence and factors associated with
      balance impairment after stroke. METHODS: Ninety-five stroke survivors undergoing
      neurorehabilitation at 2 government hospitals in Northern Nigeria participated in
      this cross-sectional study. Berg Balance Scale (BBS) was used to assess the
      presence of balance impairment (BBS score of 0-20). Prevalence of balance
      impairment was presented as frequency and percentage while demographic and stroke
      related determinants of balance impairments were identified using logistic
      regression analysis. RESULTS: Thirty-five (36.8%) stroke survivors had balance
      impairment, and age, gender, and poststroke duration were statistically
      significant determinants. Stroke survivors aged less than 40 years (odds ratio
      [OR] = .14 [confidence interval [CI] = .20-.94]) and 40-59 years (OR = .23 [CI =
      .06-.81]) had a lower likelihood of having balance impairment compared to stroke
      survivors aged 60 years and above. Similarly, males had a lower likelihood of
      having balance impairment (OR = 1.60 [CI = .05-.55]) compared to females while
      those in the acute/subacute phase of stroke had a 7-fold likelihood of having
      balance impairment (OR = 7.74 [CI = 2.63-22.79]) compared to those with chronic
      stroke. CONCLUSIONS: Poststroke balance impairment appears to be significantly
      influenced by stroke survivors' age, gender, and poststroke duration. Hence,
      these variables should be considered when planning rehabilitation strategies for
      improving balance after stroke.

PMID- 30205997
TI  - Antithrombotic Treatment Prior to Intracerebral Hemorrhage: Analysis in the
      National Acute Stroke Israeli Registry.
AB  - BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) is the most disastrous
      stroke subtype. Prognosis is considered worse with prior antithrombotic
      treatment. Our aim was to evaluate the association of prior antithrombotic
      treatment on the radiological and clinical outcome after ICH in a subgroup of
      patients included in a national registry. METHODS: Based on the National Acute
      Stroke Israeli (NASIS) registry during 2004, 2007, 2010, and 2013 (2-month
      periods), characteristics, volumetric parameters, and prognosis of a subgroup of
      patients with ICH were analyzed. RESULTS: Among the 634 patients with ICH in the
      NASIS registry, 310 (49%) were not treated previously with antithrombotic
      medications, 232 (37%) were treated with an antiplatelet agent, and 92 (14.5%)
      patients were on oral anticoagulant therapy, of them 30 patients (33%) with an
      international normalised ratio (INR) value below 2, 33 (36%) patients with an INR
      value of 2-3, and 29 patients (31%) with an INR value above 3 upon admission.
      Patients with deep hemorrhage on prior anticoagulants treatment had the highest
      probability for poor outcome at hospital discharge. Patients with low bleeding
      volume (0-30 cm3), were likely to have admission National Institute of Health
      Stroke Scale < 10 (62%), while those with higher volumes (30-59 cm3 and > 60
      cm3), had only 16.7% and 14.3% chance, respectively. We did not observe a
      significant difference between prior antithrombotic treatment and functional
      outcome at discharge, yet prior anticoagulant treatment was associated with
      higher long-term mortality rates. CONCLUSIONS: Our findings, based on a national
      registry, support the high mortality and poor outcome of anticoagulant related
      ICH.

PMID- 30205999
TI  - Brain Magnetic Resonance Imaging of Intracerebral Hemorrhagic Rats after Alcohol
      Consumption.
AB  - BACKGROUND: Alcoholism is one of the risk factors for cerebrovascular diseases.
      Our previous study demonstrated that acute alcohol intoxication enhances brain
      injury and neurological impairment in rats suffering from intracerebral
      hemorrhage (ICH). We plan to investigate the effect of chronic alcohol
      consumption (CAC) in rats with ICH by magnetic resonance imaging (MRI). METHODS:
      Sixteen Sprague-Dawley male rats were divided into 2 groups: CAC group (fed with
      10% alcohol drinking water for 4 weeks, n = 8), and Control group (plain drinking
      water, n = 8). ICH was induced by collagenase infusion into the right striata of
      all rats. Coronal T1-weighted imaging, T2-weighted imaging, T2*-weighted imaging,
      and diffusion-weighted imaging were generated with a 3.0T MRI scanner to
      investigate the changes of hemorrhagic volume and edema throughout the injury and
      recovery stages of ICH in rats. RESULTS: T2-weighted imaging is ideal for
      monitoring hematoma volume in rats. The hematoma volume was larger in the CAC
      group than in the control group (P < .001), however, did not correlate to post
      ICH progressive edema formation (P > .7), and neurological impairment (P > .28)
      between the 2 groups, respectively. DISCUSSION: Although our findings indicate
      that CAC induces larger hematoma in rats with ICH, the underlying mechanism
      should be studied in the future.

PMID- 30206000
TI  - Ischemic Stroke Predictors in Patients Presenting with Dizziness, Imbalance, and
      Vertigo.
AB  - OBJECTS: To identify predictors of acute ischemic stroke (AIS) among patients
      presenting to the Emergency Department (ED) with dizziness, imbalance, or vertigo
      (DIV) based on demographic and clinical characteristics. METHODS: We identified
      patients admitted to the hospital after presenting to the ED with DIV from the
      Statewide Planning and Research Cooperative System database of New York from 2010
      to 2014. Demographic and clinical characteristics were systematically collected.
      Multivariable logistic regression was used to determine predictors of a discharge
      diagnosis of AIS. RESULTS: Among 77,993 patients with DIV, 3857 (4.9%) had a
      discharge diagnosis of AIS. Admission presentation of imbalance, African-American
      race, history of hypertension, diabetes mellitus, hypercholesterolemia, tobacco
      use, atrial fibrillation, and prior AIS due to extracranial artery
      atherosclerosis were each positively associated with an AIS diagnosis
      independently. Factors negatively associated with an AIS discharge diagnosis
      included: admission presentation of vertigo, female sex, age > 81, history of
      anemia, coronary artery disease, asthma, depressive disorders, and anxiety
      disorders. CONCLUSIONS: Multiple potential positive and negative predictive AIS
      risk factors were identified. Combining with currently available centrally-caused
      dizziness prediction tools, these newly identified factors could provide more
      accurate AIS risk stratifying method for DIV patients.

PMID- 30206001
TI  - Management of Chronic Prostatitis/Chronic Pelvic Pain Syndrome.
AB  - Chronic prostatitis/chronic pelvic pain syndrome represents a wide range of
      clinical phenotypes and has traditionally been a diagnosis of exclusion with few
      proven remedies. Our structured, simplified approach to evaluation and management
      of this complex condition results in improved patient outcomes.

PMID- 30206002
TI  - Surgical Management of Peyronie's Disease.
AB  - When choosing a management strategy for a patient with Peyronie's disease (PD),
      it is critical to consider the phase of the disease, penile plaque
      characteristics, degree of curvature, associated deformities, stretched penile
      length, and baseline erectile function. Equally important is an understanding of
      the patient's goals and expectations. Treatment cost and duration may also be
      vital considerations for the patient. In this case, the degree of curvature and
      large calcified plaque make treatment with intralesional injection of collagenase
      Clostridium histolyticum unlikely to result in a functionally straight erection
      despite 6-7 mo of therapy. Conversely, surgery with either penile plication or
      plaque incision/partial excision and grafting can provide reliable straightening
      with 0-1 d of hospitalization and approximately 6 wk of recovery. With careful
      preoperative counseling and joint decision-making, surgical treatment of PD
      deformity can provide more complete correction in less time and at lower overall
      costs.

PMID- 30206004
TI  - Counterproductive criminal rehabilitation: dealing with the double-edged sword of
      moral bioenhancement via cognitive enhancement.

PMID- 30206003
TI  - The Value of Neutrophil to Lymphocyte Ratio in Patients Undergoing Cytoreductive
      Nephrectomy with Thrombectomy.
AB  - BACKGROUND: The neutrophil-lymphocyte ratio (NLR) is an established signature of
      inflammation used for evaluating renal cell carcinoma (RCC). OBJECTIVE: To
      determine the utility of NLR and its relationship with known risk factors
      associated with poor survival in patients with metastatic RCC and tumor thrombus
      undergoing cytoreductive nephrectomy (CN). DESIGN, SETTING, AND PARTICIPANTS:
      Prognostic variables were reviewed for patients undergoing CN with thrombectomy
      between 2000 and 2014 from six different institutions. Patients were stratified
      for NLR >4.0 based on cut point analysis. OUTCOME MEASUREMENTS AND STATISTICAL
      ANALYSIS: Kaplan-Meier curves compared overall survival of the total cohort and
      established risk models (Memorial Sloan Kettering Cancer Center [MSKCC],
      International Metastatic Renal-Cell Carcinoma Database Consortium [IMDC], and
      M.D. Anderson Cancer Center [MDACC]) stratified by NLR. Multivariable Cox
      regression determined predictors of overall survival. Receiver operator
      characteristic curves tested the predictive accuracy of survival >=12 mo, and
      area under the curve (AUC) was compared between models. RESULTS AND LIMITATIONS:
      In total, 332 patients were identified. Patients with NLR <=4.0 had longer median
      survival (24.7 vs 15.2 mo, p=0.004). NLR >4.0 distinguished patients with
      significantly shorter survival for non-poor-risk groups defined by MSKCC, IMDC,
      and MDACC criteria. Systemic symptoms, low hemoglobin, elevated lactate
      dehydrogenase, retroperitoneal adenopathy, level IV thrombus, elevated absolute
      neutrophil count, and NLR >4 were independent predictors of decreased survival
      (p<0.05). These factors had higher predictive accuracy for survival at 12 mo
      (AUC=0.755) than MKSCC, IMDC, and MSKCC models. CONCLUSIONS: NLR >4.0
      independently predicts poor survival and further distinguishes established risk
      model survival curves. We identified seven preoperative risk factors related to
      poor survival for patients with metastatic RCC with tumor thrombus undergoing CN.
      PATIENT SUMMARY: The neutrophil-lymphocyte ratio and six additional preoperative
      variables can be used to better council patients regarding survival after surgery
      for metastatic renal cell carcinoma with tumor thrombus.

PMID- 30206006
TI  - Health risk perceptions and reasons for use of tobacco products among clients in
      addictions treatment.
AB  - INTRODUCTION: We examined rates of use, health risk perceptions and reasons for
      use of combustible and non-combustible tobacco products among clients enrolled in
      addictions treatment across the United States. METHODS: Participants (N = 1153)
      completed tobacco use surveys and rated health risk perception of all products.
      Users of non-cigarette products reported their main reason for use of each
      product. Logistic regression analyses examined associations between health risk
      perceptions and product use, including combustible cigarette use, and between
      reasons for use and non-cigarette product use. RESULTS: Cigarette smoking was
      reported by 77.5%, followed by use of e-cigarettes (26.6%), little filtered
      cigars (LFCs)/cigarillos (15.4%), smokeless tobacco (11.4%), and cigars (8.4%).
      Lower perceived health risk of cigarettes was associated with smoking cigarettes
      (OR = 0.985, 95% CI: 0.975-0.995, p = 0.005). Lower perceived health risk of e
      cigarettes was associated with e-cigarette use (OR = 0.991, 95% CI: 0.984-0.998,
      p = 0.023). Users of cigars and users of LFC/cigarillos (versus other product
      use) were more likely to report their main reason for use as "enjoying flavor/
      taste", and smokeless tobacco users were more likely to report "at times when
      can't smoke" as their main reason for use compared with other reasons. E
      cigarette users were more likely to report to "reduce/quit cigarettes" as their
      main reason for use as compared to all other reasons except "reduce health risk".
      CONCLUSION: Treating smoking in addictions treatment should assess all tobacco
      product use, accuracy of health risk perceptions, and use of e-cigarettes to
      reduce/quit smoking, in order to promote cessation of combustible tobacco.

PMID- 30206005
TI  - Psychiatric care without consent in France: Does the type of administrative
      measure chosen differ according to patients' clinical profile?
AB  - The French Mental Health Law of 5 July 2011 stipulates that psychiatric patients
      can be hospitalized in five different ways. Three types of admission for
      involuntary treatment are defined under "admission at the request of a third
      party". The first is "psychiatric care at the request of a third party", followed
      by two "exceptional" admission measures in the case of an emergency ("emergency
      psychiatric care at the request of a third party") and imminent danger
      ("psychiatric care in the case of imminent danger"). The aim of this
      retrospective study was to determine whether the demographic and clinical
      characteristics of patients involuntarily admitted to psychiatric care in a
      French regional teaching hospital differed according to the administrative
      measure enabling this type of placement. We reviewed a sample of admission
      medical certificates issued between 1 July 2014 and 30 June 30, 2015 at the Tours
      University Hospital (France) for psychiatric care without consent. We recorded
      the following patient characteristics. Collected data included the type of care
      measure, age, gender, and the presence or absence of various clinical syndromes,
      such as suicidal thoughts and behavioral, depressive, manic or psychotic
      disorders. Multivariable analysis showed that a psychotic syndrome was a risk
      factor for hospitalization under "exceptional" measures and a behavioral syndrome
      for hospitalization under "psychiatric care at the request of a third party".
      Several clinical profiles emerged, but suicidal thoughts did not appear to be
      associated with the type of measures taken. In our sample, the choice of measure
      applied does not appear to rely on the only clinical observation at admission,
      contrary to what was planned in the Law.

PMID- 30206007
TI  - Intrauterine growth restriction and later cardiovascular function.
AB  - Intrauterine growth restriction is one of the most common obstetric conditions,
      affecting 7-10% of fetuses. Affected fetuses are actually exposed in utero to an
      adverse environment during the highly critical time of development and may face
      life-long health consequences such as increased cardiovascular risk in adulthood.
      Already in utero, fetuses affected by growth restriction show remodeled hearts
      with signs of systolic and diastolic dysfunction. Cardiovascular remodeling
      persist into postnatal life, from the neonatal period to adolescence, suggesting
      a primary fetal cardiac programming that might explain the increased
      cardiovascular risk later in life. In this review we summarize the current
      evidence on fetal cardiovascular programming in fetuses affected by growth
      restriction, its consequences later and possible strategies from which they could
      benefit to reduce their cardiovascular risk.

PMID- 30206008
TI  - Investigation and management of the long-term ventilated premature infant.
AB  - Bronchopulmonary dysplasia (BPD) is a common complication of prematurity, and
      despite significant advances in neonatal care over recent decades its incidence
      has not diminished. Although most affected infants have mild disease requiring a
      short period of oxygen supplementation or respiratory support, severely affected
      infants can become dependent on positive pressure support for a prolonged
      duration. In such cases, investigations should be carried out to ascertain
      whether there are secondary disease processes exacerbating the child's
      respiratory status. In case of established severe BPD, respiratory support with
      non-invasive or invasive positive pressure ventilation is required. In this paper
      we discuss the indications for, and practicalities of, the various modalities
      available. Potential cardiorespiratory sequelae of BPD include recurrent
      respiratory infections, childhood wheezing illnesses, abnormalities of lung
      structure and function, and pulmonary hypertension.

PMID- 30206009
TI  - The case for a chronobiological approach to neonatal care.
AB  - Time of day is a critical factor for most biological functions, but concepts from
      the field of chronobiology have yet to be fully translated to clinical practice.
      Circadian rhythms, generated internally and synchronised to the external
      environment, promote function and support survival in almost every living
      species. Fetal circadian rhythms can be observed in utero from 30weeks gestation,
      coupled to the maternal rhythm, but synchronise to the external environment only
      after birth. Important cues for synchronisation include the light/dark cycle, the
      timing of feeding, and exposure to melatonin in breast milk. Disruption to these
      cues may occur during admission to the neonatal intensive care unit. This can
      impair the development of circadian rhythms, and influence survival and function
      in the neonatal period, with a potential to impact health and well-being
      throughout adult life. Here we outline the rationale and evidence to support a
      chronobiological approach to neonatal care.

PMID- 30206010
TI  - Noninvasive Administration of Inhaled Nitric Oxide and its Hemodynamic Effects in
      Patients With Acute Right Ventricular Dysfunction.
AB  - OBJECTIVE: The authors aimed to assess the hemodynamic effects and demonstrate
      the feasibility of inhaled nitric oxide (iNO) in hemodynamically unstable
      patients with acute right ventricular (RV) dysfunction and to explore the safety
      profile of this approach. DESIGN: Retrospective cohort study. SETTING: Intensive
      care unit (ICU) of 2 tertiary care centers between January 2013 and 2017.
      PARTICIPANTS: All patients with RV dysfunction in whom iNO was initiated without
      invasive mechanical ventilation. INTERVENTION: Noninvasive administration of iNO.
      MEASUREMENTS AND MAIN RESULTS: Eighteen patients received the intervention during
      the study period; 8 of these patients had a pulmonary artery catheter and 2 had a
      pulse contour analysis device. Median (interquartile range) iNO concentration was
      20 (20-20) ppm, and therapy duration was 24 (12-46) hours. Most patients received
      iNO through nasal prongs (66.7%) or a high-flow nasal cannula (27.8%). Within 1
      hour, iNO reduced pulmonary vascular resistance from 219.1 to 165.4 dyn*s/cm5 (n
      = 7; p < 0.001), mean pulmonary artery pressure from 28.4 to 25.3 mmHg (n = 8; p
      = 0.01), and central venous pressure from 17.5 to 13.1 mmHg (n = 16; p = 0.001).
      Indexed cardiac output increased from 2.0 to 2.6 L/min/m2 (n = 9; p = 0.004). ICU
      mortality was 27.78%, and median ICU length of stay was 7 (5-9) days. Two
      significant bleeding episodes requiring intervention and 1 acute kidney injury
      occurred during iNO therapy. No headache was reported. CONCLUSION: Noninvasively
      administered iNO was associated with favorable hemodynamic effects in ICU
      patients with acute RV dysfunction. These results suggest the safety and
      feasibility of this therapy for which further prospective study is warranted.

PMID- 30206011
TI  - Calculation Algorithm Reduces Protamine Doses Without Increasing Blood Loss or
      the Transfusion Rate in Cardiac Surgery: Results of a Randomized Controlled
      Trial.
AB  - OBJECTIVES: The aim of the study was to investigate whether the HeProCalc
      algorithm affects heparin and protamine dosage, postoperative blood loss, and
      transfusion rate. DESIGN: Randomized controlled trial. SETTING: University
      hospital. PARTICIPANTS: The study comprised 210 cardiac surgery patients
      undergoing cardiac surgery with cardiopulmonary bypass. Twenty patients were
      excluded because of re-exploration for localized surgical bleeding (n = 9),
      violation of protocol (n = 2), aprotinin use (n = 3 and nadir body temperature
      <32 degrees C (n = 6). INTERVENTIONS: Study participants were randomly assigned
      to either traditional heparin and protamine dosage based on body weight only
      (control group) or dosage based on the HeProCalc algorithm (intervention group).
      MEASUREMENTS AND MAIN RESULTS: The initial median heparin dose was 32,500 IU
      (interquartile range [IQR] 30,000-35,000) in the intervention group compared with
      35,000 IU (IQR 30,000-37,500) (p = 0.025) in the control group. The total heparin
      dose in the intervention group was 40,000 IU (IQR 32,500-47,500) compared with
      42,500 IU (IQR 35,000-50,000) in the control group (p = 0.685). The total
      protamine dose was 210 mg (IQR 190-240) in the intervention group compared with
      350 mg (IQR 300-380) (p < 0.001) in the control group. The ratio of total
      protamine to initial dose of heparin in the intervention group was 0.62 compared
      with 1.0 (p < 0.001). The amount of chest tube bleeding after 12 postoperative
      hours was 320 mL (IQR 250-460) in the intervention group compared with 350 mL
      (IQR 250-450) (p = 0.754) in the control group. Neither the transfusion rate nor
      postoperative blood loss differed significantly between the 2 groups. CONCLUSION:
      Use of the HeProCalc algorithm reduced protamine dosage and the protamine/heparin
      ratio after cardiopulmonary bypass compared with conventional dosage based on
      weight without significant effect on postoperative blood loss or the transfusion
      rate.

PMID- 30206013
TI  - 'Meditation Training Intervention' - A necessary shift for head and neck cancer
      patients.

PMID- 30206012
TI  - Tick infestations of wildlife and companion animals in Ontario, Canada, with
      detection of human pathogens in Ixodes scapularis ticks.
AB  - The growing risk of transmission of tick-borne zoonotic pathogens to humans in
      Ontario, Canada, warrants investigations into regional tick distribution, tick
      burdens of local peridomestic animals, and prevalence of tick-borne pathogens.
      The objectives of this study were to investigate the geographic distribution and
      magnitude of tick infestations in opportunistically sampled mammalian wildlife
      and companion animals (i.e., dogs) in southern Ontario and to test these ticks
      for evidence of zoonotic tick-borne pathogens. Ticks collected from wildlife
      carcasses, live-trapped wildlife and companion animals (2015-2016), as well as
      wildlife diagnostic cases (2011-2013), were identified to species and life stage.
      Ixodes scapularis ticks were tested by real-time PCR for Anaplasma
      phagocytophilum, Babesia microti, Borrelia miyamotoi and Borrelia burgdorferi
      sensu stricto (s.s.). Amblyomma americanum ticks were tested for Ehrlichia
      chaffeensis. A total of 1687 ticks of six species were collected from 334
      animals, including 224 raccoons (n = 1381 ticks) and 50 dogs (n = 67 ticks). The
      most common tick species collected from parasitized raccoons were Ixodes texanus
      (n = 666 ticks) and Dermacentor variabilis (n = 600 ticks), which were removed
      from 58.5% (median: 2 ticks; range: 1-36) and 49.1% (median: 2 ticks; range: 1
      64) of raccoons, respectively. Of I. scapularis tested, 9.3% (4/43) were positive
      for Bo. burgdorferi s.s. and 2.3% (1/43) for A. phagocytophilum. These results
      reveal that numerous tick species parasitize common, peridomestic wildlife and
      that at least two zoonotic, tick-borne pathogens circulate in southern Ontario.
      Host-tick vector-pathogen dynamics should continue to be monitored in the face of
      global climate change, landscape alterations and expanding human populations.

PMID- 30206015
TI  - Infectious Complications of EVAR are Deadlier than Those of Conventional Surgery.

PMID- 30206014
TI  - Survival and arrhythmic risk among ischemic and non-ischemic heart failure
      patients with prophylactic implantable cardioverter defibrillator only therapy: A
      propensity score-matched analysis.
AB  - BACKGROUND: Concerns about the efficacy of prophylactic ICD in non-ischemic
      cardiomyopathy (NICM) heart failure (HF) patients are still present. We aimed to
      assess whether survival and arrhythmic risk were different among ischemic
      cardiomyopathy (ICM) and NICM ICD-only patients, along with specific predictors
      for mortality. METHODS: HF patients undergoing ICD-only implant were extracted
      from the nationwide multicenter UMBRELLA registry. Arrhythmic events were
      collected by remote monitoring and reviewed by a committee of experts. RESULTS:
      782 patients (556 ICM; 226 NICM) were recruited: mean ejection fraction of 26.6%;
      83.4% in NYHA class II-III; mean QRS duration of 108.9 ms (only 14.9% with QRS >
      130 ms). After 4.35 years of mean follow-up, all-cause mortality rate was
      4.2%/year. In propensity-score (PS) analysis no survival differences between ICM
      and NICM subgroups appeared (mortality rates: 19.4% vs. 20%, p = 0.375). Age
      (hazard ratio [HR] = 1.02, p = 0.009), diabetes (HR = 2.61, p <= 0.001), chronic
      obstructive pulmonary disease (HR = 2.13, p = 0.002), and previous HF (HR = 2.28,
      p = 0.027) correlated with increased mortality for the entire population, however
      atrial fibrillation (AF) (HR = 2.68, p = 0.002) and chronic kidney disease (HR =
      3.74, p <= 0.001) emerged as specific predictors in NICM patients. At follow-up,
      134 patients (17.1%) were delivered a first appropriate ICD therapy (5.1%/year)
      without significant differences between ICM and NICM patients in the PS analysis
      (17.6% vs. 15.8%, p = 0.968). ICD shocks were associated with a higher mortality
      (HR = 2.88, p < 0.001) but longer detection windows (HR = 0.57, p = 0.042)
      correlated with fewer appropriate therapies. CONCLUSIONS: Mortality and
      arrhythmia free survival is similar among ICM and NICM HF patients undergoing ICD
      only implant for primary prevention strategy.

PMID- 30206016
TI  - Evidence Based Training Strategies to Improve Clinical Practice in Endovascular
      Aneurysm Repair.

PMID- 30206017
TI  - Laboratory considerations for prenatal genetic testing.
AB  - New genetic tests have rapidly entered clinical care with little consistency in
      laboratory testing and reporting. Non-invasive prenatal screening using cell free
      DNA (cfDNA) may either screen for common aneuploidies alone or include
      chromosomal microdeletions. All cfDNA screening tests have false positives and
      false negatives, and accordingly laboratories should report positive and negative
      predictive values. In addition, since fetal fraction plays a significant role in
      the reliability of results, this should also be reported with all test results.
      Chromosomal microarray addresses significant clinically relevant information
      beyond that detected with standard karyotype testing but may, in less than one
      percent of cases, result in a variant of uncertain significance (VUS).
      Laboratories should indicate their policies for reporting these VUS findings. In
      addition, physicians using this testing should be aware of the advantages and
      disadvantages of the laboratory platforms. Whole-exome and whole-genome
      sequencing are just entering clinical care and issues of VUS, incidental
      findings, and phenotype/genotype correlations need to be investigated before
      these techniques enter routine clinical care.

PMID- 30206018
TI  - Non-invasive prediction of oesophageal varices in patients with cirrhosis
      secondary to non-alcoholic fatty liver disease.

PMID- 30206019
TI  - Corrigendum to "Alveolar echinococcosis: From a deadly disease to a well
      controlled infection. Relative survival and economic analysis in Switzerland over
      the last 35 years" [J Hepatol 49 (2008) 72-77].

PMID- 30206020
TI  - A prospective longitudinal assessment of MRI signal intensity kinetics of non
      target muscles in patients with advanced stage oropharyngeal cancer in
      relationship to radiotherapy dose and post-treatment radiation-associated
      dysphagia: Preliminary findings from a randomized trial.
AB  - PURPOSE: To assess quantitative signal intensity (SI) kinetics obtained from
      serial MRI of swallowing muscles as a potential imaging biomarker of radiation
      induced dysphagia in oropharyngeal cancer (OPC) patients receiving radiotherapy
      (RT). METHODS: Patients were enrolled under an IRB approved Phase II/III
      randomized trial. Patients underwent serial MRIs at pre-, mid-, and post-RT.
      Normalized T1, T1+ contrast (T1 + C), and T2 SI for swallowing muscle volumes-of
      interest (VOIs) were collected and delta SI changes (Delta) were calculated. Mid-
      and post-RT SI relative to baseline were assessed and correlations between
      radiation dose and percent change in SI were calculated. Independent samples' t
      tests were used to compare the percent change of SI between patients divided into
      two groups based on dysphagia status post-RT. RESULTS: Forty-six patients with
      stage III/IV HPV+ OPC were included in this study. Relative to baseline, mean T2
      and T1 + C SIs for middle pharyngeal constrictor were both significantly higher
      at mid- and post-RT (p < 0.004 for all). Superior pharyngeal constrictor also
      showed a significant increase in T1 + C SI at mid-RT (p = 0.0004). Additional
      muscle VOIs showed significant changes post-RT, but not earlier at mid-RT. Both
      mid- and post-RT doses were significantly correlated with the percent change of
      normalized T2 and T1 + C SI for examined muscle VOIs (p < 0.002). Mean percent
      changes of normalized T2 SI at mid-RT relative to baseline for all muscle VOIs
      were significantly higher in patients who developed grade >=2 dysphagia relative
      to patients with no/mild dysphasia (mean Delta%: 8.2% vs 1.9%; respectively, p =
      0.002). However, at post-RT, these changes were only significant in T1 SI (11.2%
      vs -1.3%; p < 0.0001). CONCLUSION: Signal intensity kinetics of radiation injury
      can be broadly correlated with the functional muscular defect. Serial MRI during
      the course of RT may provide an opportunity to quantitatively track muscular
      pathology for subclinical detection of patients at high risk to develop
      dysphagia.

PMID- 30206021
TI  - Practical clinical guidelines for contouring the trigeminal nerve (V) and its
      branches in head and neck cancers.
AB  - PURPOSE: The trigeminal nerve (V) is a major route of tumor spread in several
      head and neck cancers. However, only limited data are currently available for its
      precise contouring, although this is absolutely necessary in the era of intensity
      modulated radiation therapy (IMRT). The purpose of this article is to present
      practical clinical guidelines for contouring the trigeminal nerve (V) in head and
      neck cancers at risk of spread along this nerve. METHOD: The main types of head
      and neck cancers associated with risks of spread along the trigeminal nerve (V)
      and its branches were comprehensively reviewed based on clinical experience,
      literature-based patterns of failure, anatomy and radio-anatomy. A consensus for
      contouring was proposed based on a multidisciplinary approach among head and neck
      oncology experts including radiation oncologists (JBi, ML, MO, VG and JB), a
      radiologist (VD) and a surgeon (CS). These practical clinical guidelines have
      been endorsed by the GORTEC (Head and Neck Radiation Oncology Group). RESULTS: We
      provided contouring and treatment guidelines, supported by detailed figures and
      tables to help, for the trigeminal nerve and its branches: the ophthalmic nerve
      (V1), the maxillary nerve (V2) and the manidibular nerve (V3). A CT- and MRI
      based atlas was proposed to illustrate the whole trigeminal nerve pathway with
      its main branches. CONCLUSION: Trigeminal nerve (V) invasion is an important
      component of the natural history of various head and neck cancers. Recognizing
      the radio-anatomy and potential routes of invasion is essential for optimal
      contouring, as presented in these guidelines.

PMID- 30206022
TI  - Solitary Fibrous Tumour: A Single Institution Retrospective Study and Further
      Validation of a Prognostic Risk Assessment System.
AB  - AIMS: Solitary fibrous tumour (SFT) is a rare mesenchymal-derived neoplasm that
      can arise in any anatomical location in the body. SFT rarely metastasises, but
      aggressive behaviour is seen in a minority of cases, and relapses can occur
      several years after treatment. It would be a clinical advantage if high-risk
      patients could be identified before treatment. MATERIALS AND METHODS: We
      retrospectively analysed a population-based cohort of SFT to describe treatment,
      outcome, prognostic factors and to further validate a previously published risk
      assessment tool (D-score) based on age, tumour size and mitotic index. Seventy
      two patients diagnosed with SFT in the Central, North and Southern Denmark
      regions between 1979 and 2013 were included in the study. RESULTS: For patients
      with localised disease at the time of diagnosis (n = 64) the 5 and 10 year
      overall survival was 86% (95% confidence interval 74-92) and 65% (95% confidence
      interval 50-78), respectively. Seventeen of 62 patients (27%) who were in
      remission after radical treatment developed recurrence with either local or
      distant disease. The 5 year recurrence-free survival was 83% (95% confidence
      interval 70-90) and the 10 year was 69% (95% confidence interval 53-81). The 5
      year local recurrence-free survival was 96% (95% confidence interval 86-99) and
      the 10 year was 92% (95% confidence interval 76-96). The median time to both
      overall recurrence and local recurrence was 4.3 years. Metastatic or inoperable
      SFT had a poor prognosis with a median overall survival of 8.4 months (range 3.6
      26.4) and a 5 year overall survival of 11% (95% confidence interval 2-30). A
      further validation of a risk assessment tool (D-score) confirmed that patients
      classified as high-risk had a significantly decreased overall survival, with a
      hazard ratio of 3.7 (95% confidence interval 1.1-12.3). CONCLUSIONS: This study
      showed that our management and outcome were comparable with other published
      studies describing SFT and confirmed the value of the D-score as a risk
      assessment tool. Because of late recurrences, long-term (e.g. 10 years) follow-up
      for moderate- and high-risk patients is recommended.

PMID- 30206023
TI  - Risk of severe primary graft dysfunction in patients bridged to heart
      transplantation with continuous-flow left ventricular assist devices.
AB  - BACKGROUND: Primary graft dysfunction (PGD) remains a significant cause of post
      transplant morbidity and mortality. The exact mechanism and risk factors for this
      phenomenon remain unknown in the contemporary era. METHODS: In this study we
      reviewed adult patients undergoing heart transplantation (HT) at our institution
      between 2009 and 2017. Severe PGD was defined as the need for mechanical
      circulatory support (MCS) within the first 24 hours after HT. Multivariate
      logistic regression analysis was used to identify risk factors for severe PGD,
      focusing on those bridged to transplant (BTT) with a continuous-flow left
      ventricular assist device (CF-LVAD). RESULTS: Fifty-six of 480 (11.7%) HT
      patients experienced severe PGD. Eighty percent of the severe PGD patients were
      BTT with a CF-LVAD (odds ratio [OR] 3.86, 95% confidence interval [CI] 1.94 to
      7.68, p < 0.001). Among the BTT patients, significant associations between >1
      year of CF-LVAD support (OR 2.48, 95% CI 1.14 to 5.40, p = 0.022), pre-HT
      creatinine (OR 3.35, 95% CI 1.42 to 7.92, p = 0.006), elevated central venous
      pressure/pulmonary capillary wedge pressure (CVP/PCWP) ratio (OR 3.32, 95% CI
      1.04 to 10.60, p = 0.043), use of amiodarone before HT (OR 2.69, 95% CI 1.20 to
      6.20, p = 0.022), and severe PGD were identified. RADIAL score did not accurately
      predict severe PGD in this contemporary cohort. Those patients who developed
      severe PGD had decreased 1-year post-transplant survival (78.3% vs 91.8%, p =
      0.007). CONCLUSIONS: Use of CF-LVAD as BTT is associated with an increased risk
      of severe PGD. Increased time on device support, renal dysfunction, right
      ventricular dysfunction as assessed by CVP/PCWP ratio, and pre-transplant
      amiodarone may identify those patients at high risk. Further research is
      warranted focusing on optimal timing of device implantation and transplantation,
      as well as the underlying mechanisms of PGD.

PMID- 30206024
TI  - Keloid formation after pediatric male genital surgeries: an uncommon and
      difficult problem to manage.
AB  - INTRODUCTION: Penile and genital keloids are uncommon despite frequent surgeries
      in the genital area. Keloid scar pathogenesis is not well understood, and a
      uniform effective therapeutic regimen for keloids has not yet been established.
      In the present study, the clinical features and subsequent management in cases of
      severe keloid formation after pediatric genital surgery are described. METHODS: A
      retrospective review of keloid cases that had developed after genital procedures
      between 2000 and 2017 was conducted. Pre-operative characteristics, operative
      procedures, postoperative management, and follow-up were reviewed for each case.
      All cases were managed by a multidisciplinary team that included plastic surgeons
      and dermatologists. RESULT: Six cases developed genital keloids. The mean age at
      surgery was 5.6 years (+/- standard deviation 4.6 years). Procedures included
      phalloplasties, penile curvature correction, penoscrotal transposition, redo
      hypospadias repair, and circumcision. Treatment options included excision of the
      keloid +/- topical steroid injections and postoperative use of silicone gel. Two
      cases of severe keloid lesions developed after using posterior auricular grafts.
      Ultimately, a successful outcome was achieved in all cases. CONCLUSION: Genital
      keloids are rare and difficult to treat. Many therapeutic options are available
      with varying degrees of proven clinical success. As a result, pediatric
      urologists must be aware of advances in other fields such as plastic surgery and
      dermatology to treat and ideally prevent the occurrence of this serious
      complication.

PMID- 30206026
TI  - Treatment Patterns and Outcomes in Stage IV Bladder Cancer in a Community
      Oncology Setting: 2008-2015.
AB  - INTRODUCTION: Current real-world data regarding treatment patterns in advanced
      bladder cancer in the community setting are limited. This study describes patient
      characteristics, treatment patterns, and effectiveness outcomes for stage IV
      bladder cancer in the community setting. METHODS: Medical records data of adults
      diagnosed with stage IV bladder cancer between January 1, 2008 and June 1, 2015
      were retrospectively collected from a network of United States community oncology
      practices. Patient characteristics, treatment patterns, and efficacy outcomes
      were assessed. Across-group comparisons were conducted using bivariate analyses.
      Kaplan-Meier and Cox regression analyses of progression-free survival and overall
      survival (OS) were conducted. RESULTS: Of 508 patients (mean age, 70 +/- 11
      years), 75.2% were male, 79.1% white, 15.4% black, and 71.5% were >= 65 years.
      The most prevalent comorbidities were diabetes (23.4%) and renal disease (16.5%).
      Overall, 56% of patients received first-line platinum-based chemotherapy; the
      most common regimen was gemcitabine/carboplatin (23.6%), followed by
      gemcitabine/cisplatin (17%). The median OS was 9.4 months from stage IV bladder
      cancer diagnosis and 8.4 months from start of first-line therapy. Cox regression
      analysis of OS from diagnosis showed a higher risk of death for patients with no
      treatment (hazard ratio [HR], 2.06; P < .0001) or other treatment (HR, 1.83; P =
      .002) versus cisplatin and for patients with impaired performance (HR, 2.05; P <
      .0001). CONCLUSION: Platinum-based chemotherapy was the most prescribed treatment
      for stage IV bladder cancer in the community setting. Several patients were not
      treated with any chemotherapy, although we did not observe the reason for no
      treatment. This study highlights an unmet need in this population, particularly
      in a relapsed/refractory setting, and the need for improvement in outcomes.

PMID- 30206025
TI  - The local microbiome after pediatric bladder augmentation: intestinal segments
      and the native urinary bladder host similar mucosal microbiota.
AB  - INTRODUCTION: Next-generation sequencing (NGS) techniques have provided novel
      insights into the microbiome of the urinary bladder (UB). In children after
      bladder augmentation using either ileum (ileocystoplasty, ICP) or colon
      (colocystoplasty, CCP), the fate of the mucosal microbiome introduced into the
      urinary tract remains unknown. OBJECTIVE: The aim was to compare the mucosal
      microbiome of the native UB vs the augmented intestinal segment (IS) using NGS.
      STUDY DESIGN: Twelve children after bladder augmentation (ICP n = 6, CCP n = 6)
      were included. Biopsies were taken during routine postoperative cystoscopy from
      the native UB and the IS. Specimens underwent whole-genome DNA extraction, 16S
      rRNA gene amplification, NGS, and Quantitative Insights Into Microbial Ecology
      (QIIME) data analysis. Downstream statistical data analyses were performed in
      Calypso. RESULTS: Patients' median age at the time of surgery was 11 years (6-17
      years), and the median interval between augmentation and sampling was 7 years (4
      13 years). alpha-Diversity (Shannon diversity index) was not significantly
      different between IS vs UB, ICP vs CCP, and male vs female. No general
      differences in the overall bacterial pattern (beta-diversity) were found between
      IS, UB, ICP, and CCP groups. The groups overlapped in principal coordinate
      analysis (PCoA) and non-metric multidimensional scaling (NMDS) analysis (Figure).
      Age at sampling had a statistically significant influence on beta-diversity at
      the genus level. Corynebacterium, Pseudoxanthomonas, Lactobacillus,
      Flavobacterium, and Micrococcus were the most dominating taxa detected over all
      samples. There was an obvious dominance of the genus Corynebacterium in the
      samples taken from the UB and IS in both ICP and CCP patients. Limitations of
      this study include the relatively small number of patients. CONCLUSION: After
      bladder augmentation, the native UB and augmented ISs (ICP and CCP) host similar
      microbiota despite their distinct differences of originating mucosal anatomy.

PMID- 30206027
TI  - Topical 3-bromopyruvate is a novel targeted therapy for melanoma in a preclinical
      model.
AB  - BACKGROUND: Targeting cancer metabolism is a promising strategy in improving
      cancer treatment. OBJECTIVE: To introduce a targeted therapy with topical 3
      bromopyruvate (3BP), aglycolytic inhibitor, into the clinic in the near future.
      METHOD: We investigated the anti-tumor efficacy of 3BP on melanoma cells in vitro
      and in a preclinical model. RESULTS: Our cell-based study demonstrated that 3BP
      showed cytotoxicity for melanoma cells under anchorage-dependent or independent
      cell growth via a reactive oxygen species-mediated and caspase-independent cell
      death pathway. Moreover, 3BP inhibited both self-renewal potential and growth of
      slow-cycling phenotype in melanoma cells. Remarkably, the preclinical mouse
      xenograft model shed light on topical application of 3BP, showing significant
      anti-tumor effects with no apparent toxicity in surrounding normal tissues.
      CONCLUSION: We have now proposed that a targeted therapy with topical 3BP is an
      innovative strategy for adjuvant chemotherapy of technically or medically
      unresectable melanoma and possibly other skin cancers.

PMID- 30206028
TI  - Intracardiac Echocardiography as Sole Guidance for the MitraClip Procedure.

PMID- 30206029
TI  - High fractional potassium excretion in symptomatic hyponatremia.

PMID- 30206030
TI  - A review on the production of nitrogen-containing compounds from microalgal
      biomass via pyrolysis.
AB  - Nitrogen-containing compounds (NCCs) which may be produced from nitrogen-rich
      biomass such as microalgae, may find important biochemical and biomedical
      applications. This review summarizes the recent knowledge about the formation
      mechanism of NCCs during pyrolysis of microalgae. The key technical and
      biological aspects of microalgae and pyrolysis process parameters, which
      influence the formation of NCCs, have been analyzed. The mechanism of formation
      of NCCs such as indole, pyridine, amides, and nitriles during primary and
      secondary pyrolysis reactions are elaborated. It has been emphasized that the
      pyrolysis conditions and the use of catalysts had significant impacts on the
      yields and compositions of NCCs. The available information shows that the
      transformation of nitrogen and nitrogen functionalities during pyrolysis are
      strongly associated with the formation process of NCCs. The challenges in the
      development of pyrolysis technologies for the production of NCCs from microalgae
      are identified with future research needs identified.

PMID- 30206031
TI  - Removal of bioavailable dissolved organic nitrogen in wastewater by membrane
      bioreactors as posttreatment: Implications for eutrophication control.
AB  - Bioavailable dissolved organic nitrogen (ABDON) is the component of dissolved
      organic nitrogen (DON) which supports the growth of algae. Previous research
      indicates that a membrane bioreactor (MBR) is effective in reducing DON, however,
      its ability to remove ABDON remains unknown. The present study investigated three
      full-scale MBRs (membrane type: hydrophilic polyvinylidene fluoride and membrane
      pore size: 0.04-0.1 um) as posttreatment for the removal of ABDON. Results showed
      that the concentrations of ABDON were not significantly different between
      influent and effluent at each MBR (p = 0.067-0.614, t-test). Analysis of DON
      molecular composition via ultrahigh resolution mass spectrometry provides
      supporting evidence that bacterial biomass produced/released ABDON during the
      biological processes, which would be one of the possible reasons for the low
      removal efficiency of ABDON (<0%-14.0%) occurred in the MBR process. Overall,
      MBRs as posttreatments would have a smaller-than expected impact on primary
      productivity in receiving waters since a substantial fraction of DON stimulating
      algal growth cannot be removed by this treatment.

PMID- 30206032
TI  - Nicotine is neuroprotective to neonatal neurons of sympathetic ganglion in rat.
AB  - Sympathetic neurons of SCG are dependent on availability of nerve growth factor
      (NGF) for their survival. SCG neurons express nicotinic receptors (nAChR) whose
      expression levels are modulated by nicotine. Nicotine exerts multiple effects on
      neurons, including neuroprotection, through nAChR binding. Although sympathetic
      neurons express robust levels of nAChR, a possible neuroprotective role for
      nicotine in these neurons is not well-understood. Therefore we determined the
      effect of nicotine exposure on survival of SCG neurons during NGF withdrawal in a
      well-established cell culture system. NGF was withdrawn in rat neonatal SCG
      neuron cultures which were then treated with either 10 MUM nicotine alone or with
      nAChR antagonists 0.1 MUM alpha-bungarotoxin (antagonist for alpha7 subunit
      bearing nAChR) and 10 MUM mecamylamine (non-specific antagonist for ganglionic
      nAChR) for 48 h. Apoptotic death was determined by TUNEL staining. Cell survival
      was also determined by MTS assay. Western blot analysis of ERK1/2 was also
      performed. Our results showed that exposure to 10 MUM nicotine significantly
      reduced apoptotic cell death in SCG neurons resulting from NGF withdrawal as
      shown by fewer TUNEL positive cells. The MTS assay results also revealed that 10
      MUM nicotine concentration significantly increased cell survival thus indicating
      neuroprotective effect of nicotine against cell death resulting from NGF
      withdrawal. Nicotinic receptor antagonists (bungarotoxin & mecamylamine)
      attenuated the effect of nicotine's action of neuroprotection. Western blot
      analysis showed an increased expression of ERK1/2 in nicotine treated cultures
      suggesting nicotine provided neuroprotection in SCG neurons by increasing the
      expression of ERK1/2 through nicotinic receptor dependent mechanisms.

PMID- 30206033
TI  - Quick and Simple FRAIL Scale Predicts Incident Activities of Daily Living (ADL)
      and Instrumental ADL (IADL) Disabilities: A Systematic Review and Meta-analysis.
AB  - OBJECTIVES: To quantitatively examine frailty defined by FRAIL scale as a
      predictor of incident disability risks by conducting a systematic review and meta
      analysis. DESIGN: Systematic review and meta-analysis. SETTING: A systematic
      review was conducted using 4 electronic databases (Embase, MEDLINE, CINAHL, and
      PsycINFO) in April 2018 for prospective cohort studies of middle-aged or older
      people examining associations between frailty and incident disability. Reference
      lists of the included studies were hand-searched for additional studies. Authors
      of potentially eligible studies were contacted for additional data if necessary.
      Methodological quality was assessed by the Newcastle-Ottawa scale. PARTICIPANTS:
      Community-dwelling middle-aged and older people. MEASUREMENTS: Incident risks of
      activities of daily living (ADL) or instrumental activities of daily living
      (IADL) disability according the FRAIL scale-defined frailty. RESULTS: Seven
      studies provided odds ratios of incident disability risks according to frailty
      and were included in the meta-analysis. A random effects meta-analysis showed
      that frailty and prefrailty were significant predictors of ADL [pooled odds ratio
      (OR) = 9.82, 95% confidence interval (CI) = 4.71-20.46, P < .001 for frailty
      (FRAIL scale = 3-5) and pooled OR = 2.08, 95% CI = 1.77-2.45, P < .001 for
      prefrailty (FRAIL scale = 1-2) compared with robustness (FRAIL scale = 0); pooled
      OR = 4.44, 95% CI = 3.26-6.04, P < .001 for frailty compared with nonfrailty
      (FRAIL scale = 0-2)] and IADL (pooled OR = 2.50, 95% CI = 1.67-3.73, P < .001,
      for frailty and pooled OR = 1.74, 95% CI = 1.10-2.77, P = .02, for prefrailty
      compared with robustness). There was no evidence of publication bias.
      CONCLUSIONS/IMPLICATIONS: The current study demonstrated that frailty status
      defined by the FRAIL scale was a significant predictor of disability among
      community-dwelling middle-aged and older individuals. In light of feasibility of
      the FRAIL scale, especially in a clinical setting, it may be a promising tool to
      facilitate the translation of frailty research into clinical practice.

PMID- 30206034
TI  - Matching into an Orthopedic Residency: Which Application Components Correlate
      with Final Rank List Order?
AB  - OBJECTIVE: To determine if any of the unique elements of the applications of
      medical students who were granted interviews to an orthopedic residency program
      correlate to the program's final rank order list of candidate residents. DESIGN:
      Eight domains of the standard residency application were considered as
      independent variables for 36 applicants. Personal, identifying information was
      removed from the application material within each domain, thus blinding the
      application domains for 5 core faculty members from the program to review and
      rank independently. These 8 domain rank lists were then compared to the program's
      final rank list order to determine the correlation of each domain with the final
      rank list order. SETTING: Academic medical center. PARTICIPANTS: Applicants to a
      university-based orthopedic surgery residency program who were granted interviews
      in the 2016 academic year. RESULTS: Two domains of the application correlated
      with the final rank list order: interview and personal statement. None of the
      other domains had a significant correlation with the final rank list order.
      Interobserver variability among the faculty members was high for the rankings of
      the different domains. CONCLUSIONS: Interview and personal statement were the
      only domains within the application that had correlation with the final rank list
      for an orthopedic residency program. A better understanding of how these 2
      components affect the rank list may provide opportunity for process improvements.

PMID- 30206035
TI  - Magnetic Resonance Imaging Combined With Second-look Ultrasonography in
      Predicting Pathologic Complete Response After Neoadjuvant Chemotherapy in Primary
      Breast Cancer Patients.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) or ultrasonography (US) alone is
      limited in the ability to predict the pathologic complete response (pCR)
      accurately after neoadjuvant chemotherapy (NAC). The aim of the present study was
      to predict the pCR using MRI combined with second-look US in primary breast
      cancer patients. MATERIALS AND METHODS: A total of 1274 consecutive primary
      breast cancer patients who were examined by MRI and second-look US before and
      after NAC and had undergone breast-conserving surgery from 2004 to 2014 were
      included. The positive predictive value (PPV) of a clinical complete response
      (cCR) by MRI alone and MRI plus US was assessed. A CR was defined as no residual
      invasive carcinoma. The presence of a residual in situ component was also
      assessed (ypTis). RESULTS: Of the 1274 patients, 333 (26.1%) had a pCR (ypT0/is),
      and 102 (8.0%) had a residual in situ component (ypTis). A cCR was found in 247
      patients (19.4%) using MRI alone and in 182 patients (14.3%) using MRI plus US.
      The PPV for a cCR using MRI alone was 79.4% and the PPV for MRI plus US was
      86.8%. The PPV for a cCR by MRI plus US was the greatest at 98.1% in the estrogen
      receptor-negative (ER-)/human epidermal growth factor receptor-positive (HER2+)
      group (86.5% in the ER+/HER2+, 83.0% in the ER-/HER2-, and 64.7% in the ER+/HER2-
      groups). The PPV for residual in situ component was as low as 72.2%. CONCLUSION:
      Our results have shown that MRI combined with second-look US in predicting for a
      pCR was useful compared with MRI alone, especially for ER-/HER2+. However, it was
      difficult to predict for the presence of a residual in situ component. Our
      ongoing prospective multi-institutional study has shown that adding vacuum
      assisted biopsy to MRI plus second-look US is warranted to improve the prediction
      of pCR for omitting breast surgery.

PMID- 30206036
TI  - [Pneumonia ward round: A case presentation].

PMID- 30206037
TI  - [Hypersensitivity to non-steroidal anti-inflammatory drugs, food allergy and mast
      cell activation syndrome: Relevance of the full allergy testing panel and a brief
      review of the subject, including two clinical case reports].

PMID- 30206038
TI  - [Available resources for the management of chronic obstructive pulmonary disease
      exacerbations in Spain].
AB  - OBJECTIVE: Chronic obstructive pulmonary disease exacerbations (COPDE) lead to a
      high use of healthcare resources. This study assesses the healthcare and
      organisational resources of Spanish health care centres for the management of
      COPDE at different care levels (Primary Care (PC), Respiratory Diseases, Internal
      Medicine, and Emergency Departments), and compare with current recommendations.
      MATERIAL AND METHODS: An observational study was carried out through telephone
      interviews to General Practitioners, Chest Diseases, Internal Medicine, and
      Emergency Department doctors. RESULTS: A total of 284 doctors were interviewed.
      According to their responses, at PC centres there is a high availability of pulse
      oximetry (98.9%) and electrocardiograph (100%), and a low availability of Chest X
      Ray (19.1%), or urgent laboratory tests (17.0%) in sites. In hospital wards, non
      invasive mechanical ventilation (NIV) availability was 76.1%, with only a 69.7%
      of nursing staff properly trained in its use. Respiratory intermediate care units
      (RICUs) were available in 18.3% of public hospitals versus 41.7% of private
      hospitals. Specific training for COPDE management was received by 47.9% of
      Emergency Department doctors in the previous year. Only 31.9% of PC centres had
      specific protocols for referring patients to specialists. More than 35% of PC
      centres and hospitals do not have their electronic medical records integrated
      with other healthcare levels. CONCLUSIONS: In general terms, there are sufficient
      resources available in Spanish healthcare centres. However, several areas of
      improvement were identified, such as an insufficient level of electronic medical
      record integration between healthcare levels, limited implementation of RICUs in
      public hospitals, and deficiencies related to specific training in NIV
      management.

PMID- 30206039
TI  - [Skin toxicity secondary to an overdose of omeprazole: An atypical course].

PMID- 30206040
TI  - Dengue modeling in rural Cambodia: Statistical performance versus epidemiological
      relevance.
AB  - Dengue dynamics are shaped by the complex interplay between several factors,
      including vector seasonality, interaction between four virus serotypes, and
      inapparent infections. However, paucity or quality of data do not allow for all
      of these to be taken into account in mathematical models. In order to explore
      separately the importance of these factors in models, we combined surveillance
      data with a local-scale cluster study in the rural province of Kampong Cham
      (Cambodia), in which serotypes and asymptomatic infections were documented. We
      formulate several mechanistic models, each one relying on a different set of
      hypotheses, such as explicit vector dynamics, transmission via asymptomatic
      infections and coexistence of several virus serotypes. Models are confronted with
      the observed time series using Bayesian inference, through Markov chain Monte
      Carlo. Model selection is then performed using statistical information criteria,
      and the coherence of epidemiological characteristics (reproduction numbers,
      incidence proportion, dynamics of the susceptible classes) is assessed in each
      model. Our analyses on transmission dynamics in a rural endemic setting highlight
      that two-strain models with interacting effects better reproduce the long term
      data, but they are difficult to parameterize when relying on incidence cases
      only. On the other hand, considering the available data, incorporating vector and
      asymptomatic components seems of limited added-value when seasonality and
      underreporting are already accounted for.

PMID- 30206041
TI  - Does it get better with age? Women's experience of communication in maternity
      care.
AB  - BACKGROUND: Communication with maternity care providers is one of the strongest
      predictors of the perceived quality of maternity care. There is evidence that
      older mothers experience better communication than younger mothers, but no
      evidence for why this occurs. AIM: To identify differences between younger (<35
      years) and older (35+ years) mother's perceived quality of communication and any
      apparent age-related differences. METHODS: We analysed cross-sectional data from
      2504 first-time mothers in the Having a Baby in Queensland Survey 2012. Binary
      logistic regression assessed associations between maternal age and perceived
      optimal communication (information, participation, and connection) from care
      providers during women's most recent pregnancy and birth. Multivariable logistic
      regression modelling determined the effect of potential confounders (model of
      care, mode of birth, maternal age, and risk perceptions) on associations between
      age and communication quality. FINDINGS: After adjustment for confounders, older
      mothers were more likely to report experiencing optimal information (e.g., not
      receiving conflicting information) and connection with caregivers (e.g.,
      comfortable asking questions) in both pregnancy and birth. There were no age
      related differences in the perception of participation. Model of care and mode of
      birth were more influential than maternal age in predicting communication
      perceptions. Women who used midwifery or private obstetric models and had
      unassisted vaginal births were more likely to perceive optimal communication.
      CONCLUSION: Given the benefits of communication on maternity care, redressing
      these age-related differences should be a focus of future communication training
      for care providers to ensure that women receive optimal communication, regardless
      of their age.

PMID- 30206042
TI  - Rapid and Highly Sensitive Detection of Therapeutically Relevant Oncogenic Driver
      Mutations in EBUS-TBNA Specimens From Patients With Lung Adenocarcinoma.
AB  - BACKGROUND: First-line afatinib treatment prolongs overall survival in patients
      with metastatic non-small-cell lung cancer (NSCLC) harboring exon 19 deletion of
      epidermal growth factor receptor (EGFRdelEx19) mutations. In contrast, Kirsten
      rat sarcoma 2 viral oncogene homolog (KRAS) mutations are negative predictors for
      benefit from EGFR-targeting agents. Endobronchial ultrasound-guided
      transbronchial needle aspiration (EBUS-TBNA) is well-established for lung cancer
      diagnosis and staging. Next generation sequencing (NGS) allows for simultaneous
      interrogation for multiple mutations but has limitations (required tumor tissue
      amount, assay times). Reverse transcription polymerase chain reaction (RT-PCR)
      using light-Cycler technology (LCRT-PCR) can rapidly and sensitively detect
      somatic mutations from NSCLC patients. In the present study, we analyzed the
      feasibility of LCRT-PCR for rapid EGFRdelEx19 and KRAS exon 2 mutation detection
      in EBUS-TBNA samples and compared the LCRT-PCR and NGS results. MATERIALS AND
      METHODS: A total of 48 EBUS-TBNA samples from 47 patients with a confirmed
      diagnosis of pulmonary adenocarcinoma were analyzed using LCRT-PCR (as previously
      described) and NGS (MiSeq; Illumina) using targeted resequencing and a customized
      multiplex PCR panel. The processing time was ~1 week for the NGS and < 24 hours
      for the LCRT-PCR analyses. RESULTS: All (100%) EGFRdelEx19 and KRAS exon 2
      mutations detected by NGS were detected by LCRT-PCR. In addition, LCRT-PCR
      detected 2 KRAS exon 2 mutations and 3 EGFRdelEx19 mutations that were not
      detected by NGS. CONCLUSION: LCRT-PCR is a highly sensitive method to rapidly
      detect mutations of therapeutic relevance (eg, EGFRdelEx19 and KRAS exon 2) in
      EBUS-TBNAs from NSCLC patients. It is of value as an initial assay for first-line
      treatment decisions.

PMID- 30206043
TI  - Sex-Dependent Staging in Non-Small-Cell Lung Cancer; Analysis of the Effect of
      Sex Differences in the Eighth Edition of the Tumor, Node, Metastases Staging
      System.
AB  - INTRODUCTION: Non-small-cell lung cancer (NSCLC) has disproportionately negative
      outcomes in men compared with women. The importance of the relationship between
      sex and tumor, node, metastases (TNM) staging system remains unknown. The
      objective of this study was to investigate the effect of sex on NSCLC survival
      for each stage in the eighth edition of the TNM staging system in NSCLC. PATIENTS
      AND METHODS: Two cohorts treated surgically with curative intent between 2000 and
      2010 were analyzed. The primary cohort was from Australia with a second
      population set from the Surveillance, Epidemiology, and End Results (SEER)
      database. Univariate and multivariate analyses of putative and validated
      prognostic factors were undertaken to investigate sex-dependent prognostication
      with detailed analyses of sex differences in each TNM stage. The primary outcome
      was disease-specific survival (DSS) at 5 years. RESULTS: Inclusion criteria were
      met by 555 patients in the Australian cohort, 335 men (60.4%) and 220 (39.6%)
      women; and 47,706 patients from the SEER cohort, 24,671 men (51.7%) and 23,035
      women (48.3%). Five-year DSS was significantly worse for men in multivariate
      analyses for the Australian (hazard ratio [HR], 1.44; 95% confidence interval
      [CI], 1.04-1.98; P = .026) and SEER (HR, 1.24; 95% CI, 1.20-1.28; P < .001)
      cohorts. Detailed analysis of TNM stage sex differences revealed a consistent
      pattern of men having worse survival than women across stages in both cohorts.
      CONCLUSION: The poorer survival in men with NSCLC presents research and clinical
      communities with an important challenge. This study's findings suggest that for
      men and women diagnosed with NSCLC, and managed surgically, stage-specific
      outcomes should be quoted separately and consideration to a rapid prognostic
      score with sex combined with staging as a key element.

PMID- 30206044
TI  - Docetaxel Plus RAmucirumab With Primary Prophylactic Pegylated Granulocyte-ColONy
      Stimulating Factor Support for Elderly Patients With Advanced Non-small-cell Lung
      Cancer: A Multicenter Prospective Single Arm Phase II Trial: DRAGON Study
      (WJOG9416L).
AB  - We exhibit our ongoing multicenter, prospective, single-arm, phase II trial of
      docetaxel plus ramucirumab with primary prophylactic pegylated-granulocyte-colony
      stimulating factor (PEG-G-CSF) support for chemotherapy-naive elderly patients
      with advanced non-small-cell lung cancer (NSCLC) (University Hospital Medical
      Information Network database: UMIN000030598). Docetaxel monotherapy is the
      Japanese standard of care for chemotherapy-naive elderly patients with advanced
      NSCLC. Docetaxel plus ramucirumab showed superior survival benefit over docetaxel
      monotherapy in the second-line setting for NSCLC. A Japanese phase II study
      comparing docetaxel plus ramucirumab and docetaxel monotherapy in the second-line
      setting showed febrile neutropenia (FN) incidence of approximately one-third in
      the docetaxel plus ramucirumab arm. Docetaxel plus ramucirumab could be a
      promising candidate for elderly patients with NSCLC, but such high FN incidence
      is a clinically critical concern. To overcome this problem, we adopt a routine
      primary prophylactic PEG-G-CSF with docetaxel plus ramucirumab therapy. We
      hypothesize that primary prophylactic PEG-G-CSF reduces FN and maximizes the
      efficacy of docetaxel plus ramucirumab in Japanese elderly patients with NSCLC.
      Intravenous docetaxel (60 mg/m2, day 1) plus ramucirumab (10 mg/kg, day 1) with
      subcutaneous PEG-G-CSF (3.6 mg, day 2) every 3 weeks is administered until
      progression. The primary endpoint is overall response rate (ORR). We decided the
      threshold ORR to be 20%, and the expected ORR 35%. Taking statistical points
      (alpha/beta errors: 0.05/0.80) and ineligible patients into account, the sample
      size was set at 65. When the study results are promising, we will conduct a phase
      III trial to compare docetaxel plus ramucirumab with PEG-G-CSF support versus
      docetaxel monotherapy for chemotherapy-naive elderly patients with NSCLC.

PMID- 30206045
TI  - Scoring System Based on Post-Transplant Complications in Patients after
      Allogeneic Hematopoietic Cell Transplantation for Myelodysplastic Syndrome: A
      Study from the SFGM-TC.
AB  - PURPOSE: We developed a prognostic scoring system to evaluate the prognosis of
      myelodysplastic syndrome (MDS) patients surviving more than 100 days allogeneic
      hematopoietic cell transplantation after (allo-HCT). PATIENTS AND METHODS: We
      performed a landmark analysis on a derivation cohort of 393 cases to identify
      prognostic factors for 3-year overall survival. Potential predictor variables
      included demographic and clinical data, transplantation modalities and early post
      transplant complications. The scoring system was tested against a validation
      cohort which included 391 patients. RESULTS: Complications occurring before day
      100 such as relapse [HR = 6.7; 95%CI, 4.5-10.0] (4 points), lack of platelet
      recovery [HR, 3.6; 95%CI, 2.2-5.8] (2 points), grade-II acute GVHD [HR = 1.7;
      95%CI, 1.2-2.5] (1 point) and grade-III/IV [HR = 2.6; 95%CI, 1.8 -3.8] (2 points)
      were the only independent predictors of 3-year OS. The 3-year OS associated with
      low (0), intermediate (1-3) and high (>=4) risk scores was respectively 70%, 46%
      and 6%. The model performed consistently in both cohorts, with good calibration.
      CONCLUSION: This post-transplant scoring system is a powerful predictor of
      outcome after allo-HCT for MDS, and can provide useful guidance for clinicians.
      Additional studies are required to evaluate this scoring system for other
      hematologic malignancies.

PMID- 30206046
TI  - Site specific diagnostic yield of endoscopic biopsies in Gastrointestinal Graft
      versus-Host Disease: A tertiary care Center experience.
AB  - BACKGROUND: Gastrointestinal (GI) graft versus host disease (GVHD) occurs in up
      to 40% of patients undergoing allogenic hematopoietic stem cell transplantation
      (HSCT). However, the optimal endoscopic approach is still unclear and the area of
      the GI tract with the highest diagnostic yield is still a topic of debate.
      OBJECTIVE: We compared the diagnostic yield of different anatomic site biopsies
      in the diagnosis of GI GVHD and assessed the correlation of endoscopic findings
      with histopathology. METHODS: All cases of biopsy proven GI GVHD were obtained
      from pathology database AUBMC between 1/1/2005 and 31/8/2017. We retrospectively
      analyzed the demographical, clinical and endoscopic data. RESULTS: Nineteen
      patients were diagnosed with GI GVHD over 17.6 years. The most common presenting
      symptom was severe diarrhea (18 patients, 94.7%). Combining upper endoscopy and
      sigmoidoscopy with biopsies had the highest diagnostic yield of 90% in diagnosing
      GI GVHD compared to 63.6%, 78.6% and 77.8% for upper endoscopy, sigmoidoscopy and
      colonoscopy respectively. In macroscopically normal mucosa, the recto-sigmoid and
      duodenal biopsies had the highest diagnostic yield (75%). As for the
      macroscopically abnormal mucosa, the highest yield was for the recto-sigmoid
      biopsies (100%) in lower endoscopy and duodenal biopsies in the upper endoscopy
      (60%). CONCLUSION: In a patient suspected to have GI GVHD, the best endoscopic
      approach is the combination of upper endoscopy and flexible sigmoidoscopy with
      biopsies of normal as well as abnormal mucosa. It should be emphasized that
      normal mucosa be biopsied especially in the duodenum and recto-sigmoid for a
      better diagnostic yield.

PMID- 30206047
TI  - Spontaneous and IVF pregnancies have comparable first trimester screening
      profiles for Down syndrome
AB  - OBJECTIVE: We aimed to compare the first trimester screening profiles of
      spontaneous (n=972) and IVF pregnancies (n=339) in a population of patients who
      had uncomplicated singleton pregnancies comparable for maternal age, gestation,
      BMI, and ethnicity. MATERIAL AND METHODS: A non-interventional analysis of
      retrospective cohort data and review of the literature. RESULTS: All IVF
      pregnancies were achieved via ICSI using the same ovarian stimulation protocol
      with recombinant FSH and a GnRH antagonist, cetrorelix acetate. The means of the
      multiple of median (MoM) of PAPP-A were slightly lower in the fresh (1.19+/-0.6
      vs. 1.33+/-0.7, respectively; p=0.056) and frozen ET (1.03+/-0.5 vs. 1.33+/-0. 7,
      respectively; p=0.036) IVF pregnancies compared with natural conceptions.
      However, when the medians of the MoMs of PAPP-A and beta-hCG, and their
      distributions were compared across the mode of conception, there were no
      differences between IVF pregnancies spontaneous pregnancies. Furthermore, the
      scatterplot diagram and curve fitting regression analyses revealed no difference
      in the temporal relations of beta-hCG and PAPP-A with each other and gestational
      age between spontaneous and IVF pregnancies. CONCLUSION: These results support
      the notion that uncomplicated singleton IVF pregnancies have similar first
      trimester screening profiles to spontaneous conceptions.

PMID- 30206048
TI  - Histomorphometric evaluation of MMP-9 and CD31 expression during healing under
      Negative Pressure Wound Therapy in dogs.
AB  - INTRODUCTION: The aim of the study was to evaluate the molecular and histological
      effects of negative pressure wound therapy (NPWT) on vascularisation in clinical
      cases of open wound treatment in dogs. Open wounds (n=10) were randomly assigned
      to one of two groups: NPWT treatment (n=5) or foam treatment (polyurethane-foam
      dressing, n=5). Wounds were matched based on age and underlying cause and
      analysed with respect to neovascularisation (CD31) and matrix proteinase changes
      (MMP-9). Histological slides were blinded and analysis was performed using
      automated histomorphometric software. Values determined at day zero after
      debridement were used as a reference and wound development at day six was
      evaluated using linear mixed models. Signalment, pre-treatment time and
      underlying cause were similar between groups. NPWT resulted in a highly
      significant increase of vascularisation (p.

PMID- 30206049
TI  - [Arthroscopic-assisted stabilization of medial shoulder instability in a
      Miniature Poodle].
AB  - INTRODUCTION: A 12-year old female miniature Poodle was presented because of a
      4/4 right fore-limb lameness. The orthopedic examination demonstrated pain at
      palpation of the right shoulder and an abduction angle of 55  degrees . MRI
      examination confirmed injuries consistent with a traumatic medial shoulder
      instability with no evidence of shoulder dysplasia. A partial rupture of the
      subscapularis tendon and complete detachment of the cranial gleno- humeral
      ligament were confirmed with arthroscopy. The joint was successfully stabilized
      using an arthroscopic assisted prosthetic suture.

PMID- 30206050
TI  - [Possibilities of diagnostics in unilateral fibular-nerve-paresis in a calf].
AB  - INTRODUCTION: The present case report describes the workup of unilateral fibular
      nerve-paresis in a female neonatal Fleckvieh calf. The calf was admitted to the
      Clinic for Ruminants with Ambulatory and Herd Health Services, Ludwig-
      Maximilians-University Munich as part of an investigation into a herd problem.
      The herd problem was presented as movement disorder in neonatal calves with an
      incidence of 10%. A physical, hematological, and musculoskeletal, as well as
      neurological examination was performed, and a diagnosis of a left-sided paresis
      of the fibular-nerve (N. fibularis) was made. Further special examinations
      including sonography, magnetic resonance tomography and muscle, lymph node, and
      nerve biopsies of the affected limb of the calf were also carried out. Advanced
      imaging examinations suggested the presence of inflammatory changes caudal to the
      left stifle joint in the region of the fibular nerve. Histopathological
      examination of the nerve biopsy confirmed the presence of a fibular-nerve
      neuritis. Inflammatory changes in the ischiocrural-muscles were most likely
      injection-induced, consistent with the history of the veterinary practitioner and
      the examination results.

PMID- 30206051
TI  - Bacillus anthracis as a cause of bovine abortion - a necropsy case requiring
      special biosafety measures.
AB  - INTRODUCTION: In spring 2017, the first case of bovine anthrax in 20 years in
      Switzerland occurred in the canton of Jura. Carcasses of anthrax-deceased animals
      should not be opened due to the formation of highly resistant spores bearing the
      risk of environmental contamination and aerosolization. Nevertheless, in the
      course of this local outbreak, one sick cow from the affected farm, whose blood
      repeatedly tested negative for Bacillus anthracis, was necropsied after
      euthanasia under special biosafety precautions at the Institute of Animal
      Pathology, Vetsuisse-Faculty Bern. Necropsy revealed ventral edema, fetal death,
      necro-hemorrhagic placentitis and necrotizing iliac lymphadenitis. Bacillus
      anthracis was isolated only from placenta and altered lymph node. The biosafety
      measures taken during and after necropsy prevented a contamination of the
      necropsy environment, which was proven with bacteriological swabs. This case
      shows that anthrax may elicit unspecific symptoms mimicking other diseases, and
      veterinarians must be aware of these non-septicemic cases.

PMID- 30206052
TI  - Case of the month: What's your diagnosis?

PMID- 30206056
TI  - Doctors who turn down flu vaccine could be redeployed.

PMID- 30206053
TI  - Using Mobile Technology to Provide Personalized Reminiscence for People Living
      With Dementia and Their Carers: Appraisal of Outcomes From a Quasi-Experimental
      Study.
AB  - BACKGROUND: Dementia is an international research priority. Reminiscence is an
      intervention that prompts memories and has been widely used as a therapeutic
      approach for people living with dementia. We developed a novel iPad app to
      support home-based personalized reminiscence. It is crucial that technology
      enabled reminiscence interventions are appraised. OBJECTIVE: We sought to measure
      the effect of technology-enabled reminiscence on mutuality (defined as the level
      of "closeness" between an adult living with dementia and their carer), quality of
      carer and patient relationship, and subjective well-being. METHODS: A 19-week
      personalized reminiscence intervention facilitated by a program of training and a
      bespoke iPad app was delivered to people living with dementia and their family
      carers at their own homes. Participants (N=60) were recruited in dyads from a
      cognitive rehabilitation team affiliated with a large UK health care
      organization. Each dyad comprised a person living with early to moderate dementia
      and his or her family carer. Outcome measurement data were collected at baseline,
      midpoint, and intervention closure. RESULTS: Participants living with dementia
      attained statistically significant increases in mutuality, quality of carer and
      patient relationship, and subjective well-being (P<.001 for all 3) from baseline
      to endpoint. Carers attained nonsignificant increases in mutuality and quality of
      carer and patient relationship and a nonsignificant decrease in subjective well
      being. CONCLUSIONS: Our results indicate that individual-specific reminiscence
      supported by an iPad app may be efficient in the context of early to moderate
      dementia. A robust randomized controlled trial of technology-enabled personalized
      reminiscence is warranted.

PMID- 30206054
TI  - A Smartphone App and Personalized Text Messaging Framework (InDEx) to Monitor and
      Reduce Alcohol Use in Ex-Serving Personnel: Development and Feasibility Study.
AB  - BACKGROUND: Self-reported alcohol misuse remains high in armed forces personnel
      even after they have left service. More than 50% of ex-serving personnel meet the
      criteria for hazardous alcohol use; however, many fail to acknowledge that they
      have a problem. Previous research indicates that interventions delivered via
      smartphone apps are suitable in promoting self-monitoring of alcohol use, have a
      broad reach, and may be more cost-effective than other types of brief
      interventions. There is currently no such intervention specifically designed for
      the armed forces. OBJECTIVE: This study sought to describe the development of a
      tailored smartphone app and personalized text messaging (short message service,
      SMS) framework and to test the usability and feasibility (measured and reported
      as user engagement) of this app in a hard-to-engage ex-serving population.
      METHODS: App development used Agile methodology (an incremental, iterative
      approach used in software development) and was informed by behavior change
      theory, participant feedback, and focus groups. Participants were recruited
      between May 2017 and June 2017 from an existing United Kingdom longitudinal
      military health and well-being cohort study, prescreened for eligibility, and
      directed to download either Android or iOS versions of the "Information about
      Drinking for Ex-serving personnel" (InDEx) app. Through the app, participants
      were asked to record alcohol consumption, complete a range of self-report
      measures, and set goals using implementation intentions (if-then plans).
      Alongside the app, participants received daily automated personalized text
      messages (SMS) corresponding to specific behavior change techniques with content
      informed by the health action process approach with the intended purpose of
      promoting the use of the drinks diary, suggesting alternative behaviors, and
      providing feedback on goals setting. RESULTS: Invitations to take part in the
      study were sent to ex-serving personnel, 22.6% (31/137) of whom accepted and
      downloaded the app. Participants opened the InDEx app a median of 15.0
      (interquartile range [IQR] 8.5-19.0) times during the 4 week period (28 days),
      received an average of 36.1 (SD 3.2) text messages (SMS), consumed alcohol on a
      median of 13.0 (IQR 11.0-15.0) days, and consumed a median of 5.6 (IQR 3.3-11.8)
      units per drinking day in the first week, which decreased to 4.7 (IQR 2.0-6.9)
      units by the last week and remained active for 4.0 (IQR 3.0-4.0) weeks.
      CONCLUSIONS: Personnel engaged and used the app regularly as demonstrated by the
      number of initializations, interactions, and time spent using InDEx. Future
      research is needed to evaluate the engagement with and efficacy of InDEx for the
      reduction of alcohol consumption and binge drinking in an armed forces
      population.

PMID- 30206058
TI  - Posterior urethral valve presenting with impacted prostatic urethral calculus: a
      diagnostic challenge.

PMID- 30206057
TI  - Perforation of small intestine due to metastatic lung carcinoma.

PMID- 30206055
TI  - Mindfulness-Based Resilience Training in the Workplace: Pilot Study of the
      Internet-Based Resilience@Work (RAW) Mindfulness Program.
AB  - BACKGROUND: The impact of mental illness on society is far reaching and has been
      identified as the leading cause of sickness absence and work disability in most
      developed countries. By developing evidence-based solutions that are practical,
      affordable, and accessible, there is potential to deliver substantial economic
      benefits while improving the lives of individual workers. Academic and industry
      groups are now responding to this public health issue. A key focus is on
      developing practical solutions that enhance the mental health and psychological
      resilience of workers. A growing body of research suggests resilience training
      may play a pivotal role in the realm of public health and prevention,
      particularly with regards to protecting the long-term well-being of workers.
      OBJECTIVE: Our aim is to examine whether a mindfulness-based resilience-training
      program delivered via the internet is feasible and engaging to a group of high
      risk workers. Additionally, we aim to measure the effect of the Resilience@Work
      Resilience@Work Mindfulness program on measures of resilience and related skills.
      METHODS: The current pilot study recruited 29 full-time firefighters.
      Participants were enrolled in the 6-session internet-based resilience-training
      program and were administered questionnaires prior to training and directly after
      the program ended. Measurements examined program feasibility, psychological
      resilience, experiential avoidance, and thought entanglement. RESULTS:
      Participants reported greater levels of resilience after Resilience@Work training
      compared to baseline, with a mean increase in their overall resilience score of
      1.5 (95% CI -0.25 to 3.18, t14=1.84, P=.09). Compared to baseline, participants
      also reported lower levels of psychological inflexibility and experiential
      avoidance following training, with a mean decrease of -1.8 (95% CI -3.78 to 0.20,
      t13=-1.94, P=.07). With regards to cognitive fusion (thought entanglement),
      paired-samples t tests revealed a trend towards reduction in mean scores post
      training (P=.12). CONCLUSIONS: This pilot study of the Resilience@Work program
      suggests that a mindfulness-based resilience program delivered via the Internet
      is feasible in a high-risk workplace setting. In addition, the firefighters using
      the program showed a trend toward increased resilience and psychological
      flexibility. Despite a number of limitations, the results of this pilot study
      provide some valuable insights into what form of resilience training may be
      viable in occupational settings particularly among those considered high risk,
      such as emergency workers. To the best of our knowledge, this is the first time a
      mindfulness-based resilience-training program delivered wholly via the internet
      has been tested in the workplace.

PMID- 30206060
TI  - Methodological challenges and updated findings from a meta-analysis of the
      association between mammographic density and breast cancer.
AB  - BACKGROUND: Mammographic density (MD) is an established predictor of breast
      cancer (BC) risk. However, there is limited information on the robustness of the
      risk associations for different study designs and the associated methodological
      challenges. METHODS: Our analysis includes 165 samples from studies published
      since 2006. We use a weakly-informative Bayesian approach to avoid unduly
      optimistic estimates of uncertainty, as found in the previous literature.
      RESULTS: While much of the published literature is based on categorical
      measurement of MD, there are tangible advantages in using continuous data in
      terms of estimate precision and relevance for different patient populations.
      Estimates based on % MD are more precise for lower density women, whereas
      absolute MD has advantages for higher density. We show that older results might
      not be a good proxy for current and future findings and it would be pertinent to
      adjust clinical interpretations based on the older data. CONCLUSIONS: Using an
      appropriate estimation method cognisant of the importance of heterogeneity is
      critical to obtaining reliable and robust clinical findings that are relevant for
      broad patient populations. IMPACT: We find that the existing consensus from
      previous review studies has underestimated the strength and precision of MD as a
      risk marker.

PMID- 30206059
TI  - Temporal variability and stability of the fecal microbiome: the Multiethnic
      Cohort Study.
AB  - BACKGROUND: Measurement reliability and biological stability need to be
      considered when developing sampling protocols for population-based fecal
      microbiome studies. METHODS: Stool samples were collected biannually over a two
      year period and sequenced for the V1-V3 region of the 16S rRNA gene in 50
      participants from the Multiethnic Cohort Study. We evaluated the temporal
      stability of the fecal microbiome on a community level with permutational
      multivariate analysis of variance (PERMANOVA), as well as on taxa and diversity
      measures with intraclass correlation coefficients. RESULTS: Inter-individual
      differences were the predominant source of fecal microbiome variation, and
      variation within individual was driven more by changing abundances than the
      complete loss or introduction of taxa. Phyla and diversity measures were reliable
      over the two years. Most genera were stable over time, although those with low
      abundances tended to be more dynamic. Reliability was lower among participants
      who used antibiotics, with the greatest difference seen in samples taken within
      one month of reported use. CONCLUSIONS: The fecal microbiome as a whole is stable
      over a two-year period, although certain taxa may exhibit more temporal
      variability. IMPACT: When designing large epidemiologic studies, a single sample
      is sufficient to capture the majority of the variation in the fecal microbiome
      from 16S rRNA gene sequencing, while multiple samples may be needed for rare or
      less abundant taxa.

PMID- 30206061
TI  - Individual funding request process is bad for everyone.

PMID- 30206062
TI  - Higher dairy intake is linked to lower risk of cardiovascular disease and death,
      finds study.

PMID- 30206063
TI  - Ian Gilmore quits as government alcohol adviser in opposition to industry deal.

PMID- 30206065
TI  - Drug-induced autoimmune hepatitis associated with turmeric dietary supplement
      use.
AB  - Turmeric dietary supplement sales, which accounted for US$69 million in spending
      in 2016, have been increasing exponentially in the USA, making this one of the
      most popular botanical supplements sold in the USA. Herbal supplement use, which
      is generally regarded as safe by consumers, is not usually reported to healthcare
      providers. We reported here on a case of autoimmune hepatitis, occurring in a 71
      year-old woman taking turmeric dietary supplements for the maintenance of
      cardiovascular health, which resolved rapidly following discontinuation of the
      turmeric supplements. Of particular note, turmeric use was not documented in the
      patient's medical records and the potential causative role of the turmeric
      supplementation was ultimately identified by the patient rather than the
      healthcare providers. To our knowledge, this is the first documented report of
      turmeric supplement-induced autoimmune hepatitis.

PMID- 30206066
TI  - Tubercular septal abscess in a postoperative patient: a novel entity.
AB  - Extrapulmonary tuberculosis is a rather uncommon and potentially challenging
      phenomenon. Such manifestation, particularly in the scenario of a late
      postoperative period, is extremely rare and requires a high index of suspicion,
      prompt diagnosis and appropriate treatment.We present the case scenario of a
      patient with history of successfully treated pulmonary tuberculosis many years
      earlier, without any signs of recurrence, who developed primary nasal septal
      tuberculosis after undergoing septoplasty to correct his septal deviation. His
      postoperative course remained uneventful for 4 months. He then presented with a
      spontaneous nasal septal abscess, which proved to be tubercular in nature on
      investigations. Appropriate diagnosis was established, and the patient was
      treated successfully with antituberculous therapy.Recurrent tuberculosis may
      present a diagnostic challenge for healthcare professionals. Only a high index of
      suspicion, modern diagnostic tools and institution of appropriate treatment
      including surgical intervention as required will ensure a promising outcome.

PMID- 30206067
TI  - Intracranial bleeding (ICB) as a catastrophic complication of Streptococcus
      gordonii infective endocarditis (IE) in an immunocompetent patient.
AB  - We present an interesting case of late-onset intracranial bleeding (ICB) as a
      complication of Streptococcus gordonii causing infective endocarditis. A
      previously healthy young woman was diagnosed with infective endocarditis. While
      she was already on treatment for 2 weeks, she had developed seizures with a
      localising neurological sign. An urgent non-contrasted CT brain showed massive
      left frontoparietal intraparenchymal bleeding. Although CT angiogram showed no
      evidence of active bleeding or contrast blush, massive ICB secondary to vascular
      complication of infective endocarditis was very likely. An urgent decompressive
      craniectomy with clot evacuation was done immediately to release the mass effect.
      She completed total 6 weeks of antibiotics and had postoperative uneventful
      hospital stay despite having a permanent global aphasia as a sequel of the ICB.

PMID- 30206064
TI  - The Pain Divide: a cross-sectional analysis of chronic pain prevalence, pain
      intensity and opioid utilisation in England.
AB  - OBJECTIVES: Our central research question was, in England, are geographical
      inequalities in opioid use driven by health need (pain)? To answer this question,
      our study examined: (1) if there are regional inequalities in rates of chronic
      pain prevalence, pain intensity and opioid utilisation in England; (2) if opioid
      use and chronic pain are associated after adjusting for individual-level and area
      level confounders. DESIGN: Cross-sectional study design using data from the
      Health Survey for England 2011. SETTING: England. PRIMARY AND SECONDARY OUTCOME
      MEASURES: Chronic pain prevalence, pain intensity and opioid utilisation.
      PARTICIPANTS: Participant data relating to chronic pain prevalence, pain
      intensity and opioid usage data were obtained at local authority level from the
      Health Survey for England 2011; in total, 5711 respondents were included in our
      analysis. METHODS: Regional and local authority data were mapped, and a
      generalised linear model was then used to explore the relationships between the
      data. The model was adjusted to account for area-level and individual-level
      variables. RESULTS: There were geographical variations in chronic pain
      prevalence, pain intensity and opioid utilisation across the English regions-with
      evidence of a 'pain divide' between the North and the South, whereby people in
      the North of England more likely to have 'severely limiting' or 'moderately
      limiting' chronic pain. The intensity of chronic pain was significantly and
      positively associated with the use of opioid analgesics. CONCLUSIONS: There are
      geographical differences in chronic pain prevalence, pain intensity and opioid
      utilisation across England-with evidence of a 'pain divide'. Given the public
      health concerns associated with the long-term use of opioid analgesics-and their
      questionable activity in the management of chronic pain-more guidance is needed
      to support prescribers in the management of chronic pain, so the initiation of
      opioids can be avoided.

PMID- 30206068
TI  - Penile cutaneous horn: still an enigma.

PMID- 30206069
TI  - Rare cause of gastric outlet obstruction: xanthogranulomatous cholecystitis.

PMID- 30206070
TI  - Unusual right internal carotid artery supraclinoid segment fenestration
      associated with multiple aneurysms treated with flow diversion and coiling.

PMID- 30206071
TI  - Systematic bias between blinded independent central review and local assessment:
      literature review and analyses of 76 phase III randomised controlled trials in 45
      688 patients with advanced solid tumour.
AB  - OBJECTIVE: Unbiased assessment of tumour response is crucial in randomised
      controlled trials (RCTs). Blinded independent central review is usually used as a
      supplemental or monitor to local assessment but is costly. The aim of this study
      is to investigate whether systematic bias existed in RCTs by comparing the
      treatment effects of efficacy endpoints between central and local assessments.
      DESIGN: Literature review, pooling analysis and correlation analysis. DATA
      SOURCES: PubMed, from 1 January 2010 to 30 June 2017. ELIGIBILITY CRITERIA FOR
      SELECTING STUDIES: Eligible articles are phase III RCTs comparing anticancer
      agents for advanced solid tumours. Additionally, the articles should report
      objective response rate (ORR), disease control rate (DCR), progression-free
      survival (PFS) or time to progression (TTP); the treatment effect of these
      endpoints, OR or HR, should be based on central and local assessments. RESULTS:
      Of 76 included trials involving 45 688 patients, 17 (22%) trials reported their
      endpoints with statistically inconsistent inferences (p value lower/higher than
      the probability of type I error) between central and local assessments; among
      them, 9 (53%) trials had statistically significant inference based on central
      assessment. Pooling analysis presented no systematic bias when comparing
      treatment effects of both assessments (ORR: OR=1.02 (95% CI 0.97 to 1.07),
      p=0.42, I2=0%; DCR: OR=0.97 (95% CI 0.92 to 1.03), p=0.32, I2=0%); PFS: HR=1.01
      (95% CI 0.99 to 1.02), p=0.32, I2=0%; TTP: HR=1.04 (95% CI 0.95 to 1.14), p=0.37,
      I2=0%), regardless of funding source, mask, region, tumour type, study design,
      number of enrolled patients, response assessment criteria, primary endpoint and
      trials with statistically consistent/inconsistent inferences. Correlation
      analysis also presented no sign of systematic bias between central and local
      assessments (ORR, DCR, PFS: r>0.90, p<0.01; TTP: r=0.90, p=0.29). CONCLUSIONS: No
      systematic bias could be found between local and central assessments in phase III
      RCTs on solid tumours. However, statistically inconsistent inferences could be
      made in many trials between both assessments.

PMID- 30206073
TI  - Association between serum magnesium concentration and metabolic syndrome,
      diabetes, hypertension and hyperuricaemia in knee osteoarthritis: a cross
      sectional study in Hunan Province, China.
AB  - OBJECTIVES: To examine the associations between serum magnesium (Mg)
      concentration with the prevalence of metabolic syndrome (MetS), diabetes mellitus
      (DM), hypertension (HP) and hyperuricaemia (HU) in patients with radiographic
      knee osteoarthritis (OA). METHODS: The present study was conducted at the Health
      Management Center of Xiangya Hospital. Radiographic OA was evaluated for patients
      aged over 40 years with basic characteristics and blood biochemical assessment.
      Serum Mg concentration was measured using the chemiluminescence method. MetS, DM,
      HP and HU were diagnosed based on standard protocols. The associations between
      serum Mg concentration with MetS, DM, HP and HU were evaluated by conducting
      multivariable adjusted logistic regression. RESULTS: A total of 962 patients with
      radiographic knee OA were included. Compared with the lowest quintile, the
      multivariable adjusted ORs and related 95% CIs of DM were 0.40 (95% CI 0.23 to
      0.70, p=0.001), 0.33 (95% CI 0.18 to 0.60, p<0.001), 0.27 (95% CI 0.14 to 0.52,
      p<0.001) and 0.22 (95% CI 0.11 to 0.44, p<0.001) in the second, third, fourth and
      highest quintiles of serum Mg, respectively (p for trend <0.001); the
      multivariable adjusted ORs of HU were 0.33 (95% CI 0.19 to 0.59, p<0.001), 0.52
      (95% CI 0.30 to 0.91, p=0.022) and 0.39 (95% CI 0.22 to 0.70, p=0.001) in the
      third, fourth and highest quintiles of serum Mg, respectively (p for trend
      <0.001); and the multivariable adjusted ORs of MetS were 0.59 (95% CI 0.36 to
      0.94, p=0.027) in the second and 0.56 (95% CI 0.34 to 0.93, p=0.024) in the
      highest quintiles of serum Mg. However, the inverse association between serum Mg
      and the prevalence of MetS was non-linear (p for trend=0.067). There was no
      significant association between serum Mg and HP in patients with OA. CONCLUSIONS:
      The serum Mg concentration was inversely associated with the prevalence of MetS,
      DM and HU in patients with radiographic knee OA. LEVEL OF EVIDENCE: Level III,
      cross-sectional study.

PMID- 30206072
TI  - Rationale and design of a cohort study on primary ovarian insufficiency in female
      survivors of Hodgkin's lymphoma: influence on long-term adverse effects (SOPHIA).
AB  - INTRODUCTION: Hodgkin's lymphoma (HL) has become the prototype of a curable
      disease. However, many young survivors suffer from late adverse effects of
      treatment. Both chemotherapy (CT) and radiotherapy (RT) may induce primary
      ovarian insufficiency (POI), which has been associated with reduced bone mineral
      density (BMD), neurocognitive dysfunction and possibly cardiovascular disease
      (CVD). While the general assumption is that POI increases CVD risk, other
      hypotheses postulate reverse causality, suggesting that cardiovascular risk
      factors determine menopausal age or that biological ageing underlies both POI and
      CVD risk. None of these hypotheses are supported by convincing evidence.
      Furthermore, most studies on POI-associated conditions have been conducted in
      women with early natural or surgery-induced menopause with short follow-up times.
      In this study, we will examine the long-term effects of CT-induced and/or RT
      induced POI on BMD, cardiovascular status, neurocognitive function and quality of
      life in female HL survivors. METHODS AND ANALYSIS: This study will be performed
      within an existing Dutch cohort of HL survivors. Eligible women were treated for
      HL at ages 15-39 years in three large hospitals since 1965 and survived for >=8
      years after their diagnosis. Women visiting a survivorship care outpatient clinic
      will be invited for a neurocognitive, cardiovascular and BMD assessment, and
      asked to complete several questionnaires and to provide a blood sample. Using
      multivariable regression analyses, we will compare the outcomes of HL survivors
      who developed POI with those who did not. Cardiovascular status will also be
      compared with women with natural POI. ETHICS AND DISSEMINATION: This study has
      been approved by the Institutional Review Board of the Netherlands Cancer
      Institute and has been registered at 'Toetsingonline' from the Dutch Central
      Committee on Research involving Human Subjects (file no. NL44714.031.13). Results
      will be disseminated through peer-reviewed publications and will be incorporated
      in follow-up guidelines for HL survivors.

PMID- 30206074
TI  - Clinical features, bacteriology of endotracheal aspirates and treatment outcomes
      of patients with chronic obstructive pulmonary disease and community-acquired
      pneumonia in an intensive care unit in Taiwan with an emphasis on eosinophilia
      versus non-eosinophilia: a retrospective case-control study.
AB  - OBJECTIVES: The clinical implications of blood eosinophil level in patients with
      chronic obstructive pulmonary disease (COPD) and community-acquired pneumonia
      (CAP) requiring invasive mechanical ventilation (IMV) and intensive care unit
      (ICU) admission are still unknown. Thus, this study aimed to compare the features
      of such patients with and without blood eosinophilia. DESIGN: This was a
      retrospective case-control study. SETTING: An ICU of a medical centre in central
      Taiwan. PARTICIPANTS: A total of 262 patients with COPD and CAP requiring IMV and
      ICU admission. RESULTS: Of all participants (n=262), 32 (12.2%) had an eosinophil
      percentage (EP) >2% and 169 (64.5%) had an absolute eosinophil count (AEC) >300
      cells/uL. Regardless of whether 2% or 300 cells/uL was used as a cut-off value,
      the eosinophilia group were slightly older (years) (82.9+/-5.4 vs 78.1+/-9.1,
      p=0.000 and 79.2+/-8.4 vs 77.6+/-9.6, p=0.246, respectively), and had a higher
      forced expiratory volume in 1 s/forced vital capacity (%) (56.0+/-8.0 vs 51.3+/
      11.6, p=0.005 and 53.1+/-11.2 vs 49.5+/-11.2, p=0.013, respectively), less severe
      spirometric classification (p=0.008 and p=0.001, respectively), and lower white
      cell count 109/L (8.8+/-3.2 vs 11.1+/-4.9, p=0.009 and 10.3+/-4.4 vs 11.8+/-5.3,
      p=0.017, respectively) than the non-eosinophilia group. The bacteriology of
      endotracheal aspirates showed that Pseudomonas aeruginosa and other gram-negative
      bacilli were the most common organisms in all study groups. Participants with an
      EP >2% had a shorter ICU length of stay (OR=12.13, p=0.001) than those with an EP
      <=2%, while an AEC >300 cells/uL was not associated with any in-ICUoutcomes.
      CONCLUSIONS: The results of this study have significant clinical implications and
      should be considered when making treatment decisions for the management of
      patients with COPD and CAP requiring IMV and ICU admission.

PMID- 30206076
TI  - Cross-cultural adaptation and psychometric properties of the Chinese version of
      the Communication Skills Attitude Scale among medical students in Liaoning
      province, China: a cross-sectional study.
AB  - OBJECTIVES: The aims of this study were to develop the Chinese version of the
      Communication Skills Attitude Scale (CSAS-Ch) in order to test the psychometric
      properties of the modified instrument. DESIGN: A cross-sectional study was
      conducted in September 2016 to evaluate the attitudes of Chinese medical students
      towards communication skills learning using CSAS at China Medical University.
      PARTICIPANTS: The study recruited 510 fifth-year medical students by cluster
      sampling. METHODS: Cronbach's alpha coefficients were calculated for the entire
      questionnaire and for the subscales to evaluate the internal consistency of the
      CSAS-Ch. In order to determine the structure underlying the CSAS, the scale was
      factor analysed using maximum likelihood extraction and the oblique rotation
      method. RESULTS: Of the 510 medical students, 492 (96.5%) completed the
      questionnaire. Cronbach's alpha coefficient for the CSAS scale was 0.897.
      Exploratory factor analysis showed that the four-factor structure accounted for
      59.8% of the variance and produced an acceptable fit to the data. CONCLUSIONS:
      The modified CSAS-Ch can be used to evaluate attitudes towards communication
      skills. Further Future research for improving the teaching methods for
      communication skills should explore the relationship between medical students'
      attitudes and the demographic characteristics.

PMID- 30206075
TI  - Comparison of attitudes towards five end-of-life care interventions (active pain
      control, withdrawal of futile life-sustaining treatment, passive euthanasia,
      active euthanasia and physician-assisted suicide): a multicentred cross-sectional
      survey of Korean patients with cancer, their family caregivers, physicians and
      the general Korean population.
AB  - OBJECTIVES: This study determined attitudes of four groups-Korean patients with
      cancer, their family caregivers, physicians and the general Korean population
      towards five critical end-of-life (EOL) interventions-active pain control,
      withdrawal of futile life-sustaining treatment (LST), passive euthanasia, active
      euthanasia and physician-assisted suicide. DESIGN AND SETTING: We enrolled 1001
      patients with cancer and 1006 caregivers from 12 large hospitals in Korea, 1241
      members of the general population and 928 physicians from each of the 12
      hospitals and the Korean Medical Association. We analysed the associations of
      demographic factors, attitudes towards death and the important components of a
      'good death' with critical interventions at EoL care. RESULTS: All participant
      groups strongly favoured active pain control and withdrawal of futile LST but
      differed in attitudes towards the other four EoL interventions. Physicians
      (98.9%) favoured passive euthanasia more than the other three groups. Lower
      proportions of the four groups favoured active euthanasia or PAS. Multiple
      logistic regression showed that education (adjusted OR (aOR) 1.77, 95% CI 1.33 to
      2.36), caregiver role (aOR 1.67, 95% CI 1.34 to 2.08) and considering death as
      the ending of life (aOR 1.66, 95% CI 1.05 to 1.61) were associated with
      preference for active pain control. Attitudes towards death, including belief in
      being remembered (aOR 2.03, 95% CI 1.48 to 2.79) and feeling 'life was
      meaningful' (aOR 2.56, 95% CI 1.58 to 4.15) were both strong correlates of
      withdrawal of LST with the level of monthly income (aOR 2.56, 95% CI 1.58 to
      4.15). Believing 'freedom from pain' negatively predicted preference for passive
      euthanasia (aOR 0.69, 95% CI 0.55 to 0.85). In addition, 'not being a burden to
      the family' was positively related to preferences for active euthanasia (aOR
      1.62, 95% CI 1.39 to 1.90) and PAS (aOR 1.61, 95% CI 1.37 to 1.89). CONCLUSION:
      Groups differed in their attitudes towards the five EoL interventions, and those
      attitudes were significantly associated with various attitudes towards death.

PMID- 30206077
TI  - Neighbourhood deprivation and lung cancer risk: a nested case-control study in
      the USA.
AB  - OBJECTIVES: To examine the association between neighbourhood deprivation and lung
      cancer risk. DESIGN: Nested case-control study. SETTING: Southern Community
      Cohort Study of persons residing in 12 states in the southeastern USA.
      PARTICIPANTS: 1334 cases of lung cancer and 5315 controls. PRIMARY OUTCOME
      MEASURE: Risk of lung cancer. RESULTS: After adjustment for smoking status and
      other confounders, and additional adjustment for individual-level measures of
      socioeconomic status (SES), there was no monotonic increase in risk with
      worsening deprivation score overall or within sex and race groups. There was an
      increase among current and shorter term former smokers (p=0.04) but not among
      never and longer term former smokers. There was evidence of statistically
      significant interaction by sex among whites, but not blacks, in which the effect
      of worsening deprivation on lung cancer existed in males but not in females.
      CONCLUSIONS: Area-level measures of SES were associated with lung cancer risk in
      current and shorter term former smokers only in this population.

PMID- 30206079
TI  - Conservative care with or without manipulative therapy in the management of back
      and/or neck pain in Danish children aged 9-15: a randomised controlled trial
      nested in a school-based cohort.
AB  - BACKGROUND: A substantial number of children experience spinal pain, that is,
      back and/or neck pain. Today, no 'gold-standard' treatment for spinal pain in
      children exists, but manipulative therapy is increasingly being used in spite of
      a lack of evidence of its effectiveness. This study investigates the
      effectiveness of adding manipulative therapy to other conservative care for
      spinal pain in a school-based cohort of Danish children aged 9-15 years. METHODS
      AND FINDINGS: The design was a two-arm pragmatic randomised controlled trial,
      nested in a longitudinal open cohort study in Danish public schools. 238 children
      from 13 public schools were randomised individually from February 2012 to April
      2014. A text message system and clinical examinations were used for data
      collection. Interventions included either (1) advice, exercises and soft-tissue
      treatment or (2) advice, exercises and soft-tissue treatment plus manipulative
      therapy. The primary outcome was number of recurrences of spinal pain. Secondary
      outcomes were duration of spinal pain, change in pain intensity and Global
      Perceived Effect.We found no significant difference between groups in the primary
      outcome (control group median 1 (IQR 1-3) and intervention group 2 (IQR 0-4),
      p=0.07). Children in the group receiving manipulative therapy reported a higher
      Global Perceived Effect: OR 2.22, (95% CI 1.19 to 4.15). No adverse events were
      reported. Main limitations are the potential discrepancy between parental and
      child reporting and that the study population may not be comparable to a normal
      care-seeking population. CONCLUSIONS: Adding manipulative therapy to other
      conservative care in school children with spinal pain did not result in fewer
      recurrent episodes. The choice of treatment-if any-for spinal pain in children
      therefore relies on personal preferences, and could include conservative care
      with and without manipulative therapy. Participants in this trial may differ from
      a normal care-seeking population. TRIAL REGISTRATION NUMBER: NCT01504698;
      Results.

PMID- 30206080
TI  - Violence experience by perpetrator and associations with HIV/STI risk and
      infection: a cross-sectional study among female sex workers in Karnataka, south
      India.
AB  - OBJECTIVES: Female sex workers (FSWs) experience violence from a range of
      perpetrators, but little is known about how violence experience across multiple
      settings (workplace, community, domestic) impacts on HIV/sexually transmitted
      infection (STI) risk. We examined whether HIV/STI risk differs by the perpetrator
      of violence. METHODS: An Integrated Biological and Behavioural Assessment survey
      was conducted among random samples of FSWs in two districts (Bangalore and
      Shimoga) in Karnataka state, south India, in 2011. Physical and sexual violence
      in the past six months, by workplace (client, police, coworker, pimp) or
      community (stranger, rowdy, neighbour, auto-driver) perpetrators was assessed, as
      was physical and sexual intimate partner violence in the past 12 months.
      Weighted, bivariate and multivariate analyses were used to examine associations
      between violence by perpetrator and HIV/STI risk. RESULTS: 1111 FSWs were
      included (Bangalore=718, Shimoga=393). Overall, 34.9% reported recent physical
      and/or sexual violence. Violence was experienced from domestic (27.1%), workplace
      (11.1%) and community (4.2%) perpetrators, with 6.2% of participants reporting
      recent violence from both domestic and non-domestic (workplace/community)
      perpetrators. Adjusted analysis suggests that experience of violence by
      workplace/community perpetrators is more important in increasing HIV/STI risk
      during sex work (lower condom use with clients; client or FSW under the influence
      of alcohol at last sex) than domestic violence. However, women who reported
      recent violence by domestic and workplace/community perpetrators had the highest
      odds of high-titre syphilis infection, recent STI symptoms and condom breakage at
      last sex, and the lowest odds of condom use at last sex with regular clients
      compared with women who reported violence by domestic or workplace/community
      perpetrators only. CONCLUSION: HIV/STI risk differs by the perpetrator of
      violence and is highest among FSWs experiencing violence in the
      workplace/community and at home. Effective HIV/STI prevention programmes with
      FSWs need to include violence interventions that address violence across both
      their personal and working lives.

PMID- 30206078
TI  - Human Early Life Exposome (HELIX) study: a European population-based exposome
      cohort.
AB  - PURPOSE: Essential to exposome research is the collection of data on many
      environmental exposures from different domains in the same subjects. The aim of
      the Human Early Life Exposome (HELIX) study was to measure and describe multiple
      environmental exposures during early life (pregnancy and childhood) in a
      prospective cohort and associate these exposures with molecular omics signatures
      and child health outcomes. Here, we describe recruitment, measurements available
      and baseline data of the HELIX study populations. PARTICIPANTS: The HELIX study
      represents a collaborative project across six established and ongoing
      longitudinal population-based birth cohort studies in six European countries
      (France, Greece, Lithuania, Norway, Spain and the UK). HELIX used a multilevel
      study design with the entire study population totalling 31 472 mother-child
      pairs, recruited during pregnancy, in the six existing cohorts (first level); a
      subcohort of 1301 mother-child pairs where biomarkers, omics signatures and child
      health outcomes were measured at age 6-11 years (second level) and repeat
      sampling panel studies with around 150 children and 150 pregnant women aimed at
      collecting personal exposure data (third level). FINDINGS TO DATE: Cohort data
      include urban environment, hazardous substances and lifestyle-related exposures
      for women during pregnancy and their offspring from birth until 6-11 years.
      Common, standardised protocols were used to collect biological samples, measure
      exposure biomarkers and omics signatures and assess child health across the six
      cohorts. Baseline data of the cohort show substantial variation in health
      outcomes and determinants between the six countries, for example, in family
      affluence levels, tobacco smoking, physical activity, dietary habits and
      prevalence of childhood obesity, asthma, allergies and attention deficit
      hyperactivity disorder. FUTURE PLANS: HELIX study results will inform on the
      early life exposome and its association with molecular omics signatures and child
      health outcomes. Cohort data are accessible for future research involving
      researchers external to the project.

PMID- 30206081
TI  - Optimal duration of prone positioning in patients with acute respiratory distress
      syndrome: a protocol for a systematic review and meta-regression analysis.
AB  - INTRODUCTION: Several systematic reviews and meta-analyses have demonstrated that
      prolonged (>=16 hours) prone positioning can reduce the mortality associated with
      acute respiratory distress syndrome (ARDS). However, the effectiveness and
      optimal duration of prone positioning was not fully evaluated. To fill these
      gaps, we will first investigate the effectiveness of prone positioning compared
      with the conventional management of patients with ARDS, regarding outcomes using
      the Grading of Recommendations Assessment, Development, and Evaluation (GRADE)
      system. Second, if statistical heterogeneity in effectiveness with regard to
      short-term mortality (intensive care unit death or <=30-day mortality) is shown,
      we will conduct a meta-regression analysis to explore the association between
      duration and effectiveness, and determine the optimal duration of prone
      positioning. METHOD AND ANALYSIS: Relevant studies are collected using
      PubMed/MEDLINE, Embase, Cochrane Central Register of Controlled Trials and the
      WHO International Clinical Trials Platform Search Portal. Randomised controlled
      trials comparing prone and supine positioning in adults with ARDS will be
      included in the meta-analysis. Two independent investigators will screen trials
      obtained by search eligibility and extract data from selected studies to
      standardised data recording forms. For each selected trial, the risk of bias and
      quality of evidence will be evaluated using the GRADE system. Meta-regression
      analyses will be performed to identify the most important factors associated with
      short-term mortality, and subgroup analysis will be used to analyse the
      following: duration of mechanical ventilation in the prone position per day,
      patient severity, tidal volume and cause of ARDS. If heterogeneity or
      inconsistency among the studies is detected, subgroup analysis will be conducted
      on factors that may cause heterogeneity. ETHICS AND DISSEMINATION: This study
      requires no ethical approval. The results obtained from this systematic review
      and meta-analysis will be disseminated through international conference
      presentations and publication in a peer-reviewed journal. PROSPERO REGISTRATION
      NUMBER: CRD42017078340.

PMID- 30206082
TI  - Comparative effectiveness of first-line biological monotherapy use in rheumatoid
      arthritis: a retrospective analysis of the RECord-linkage On Rheumatic Diseases
      study on health care administrative databases.
AB  - OBJECTIVE: These analyses aim to comparatively evaluate the persistence on
      treatment of different biological disease-modifying antirheumatic drugs (bDMARDs)
      when administered in monotherapy compared with combination with conventional
      synthetic disease-modifying antirheumatic drugs (csDMARDs) in rheumatoid
      arthritis (RA) patients receiving first-line biologics. DESIGN: This is a
      retrospective observational study on Administrative Healthcare Databases.
      METHODS: Data were extracted from healthcare databases of the Lombardy Region,
      Italy (2004-2013), as a part of the RECord-linkage On Rheumatic Diseases study,
      on behalf of the Italian Society for Rheumatology. Analyses included patients
      with RA starting first-line approved course of bDMARDs and evaluated drug
      survival by using Cox proportional hazard models. Results are presented as HRs
      and 95% CI, crude and adjusted for prespecified confounders (age, sex, disease
      duration, Charlson Comorbidity Index (CCI), previous infections, use of
      concomitant glucocorticoids or non-steroidal anti-inflammatory drugs (NSAIDs)).
      RESULTS: 4478 patients with RA were included (17.84% monotherapy). Etanercept,
      adalimumab and infliximab were the most prescribed first-line biologics. bDMARD
      monotherapy was associated with longer disease duration, higher CCI, lower
      glucocorticoids and NSAIDs use. Compared with monotherapy, combination associated
      with a lower risk of failure (adjusted HR 0.79, 95% CI 0.72 to 0.88). Among
      monotherapies, considering etanercept as reference, adalimumab (1.28, 95% CI 1.03
      to 1.59) and infliximab (2.41, 95% CI 1.85 to 3.15) had higher risk of failure.
      Concomitant methotrexate (0.78, 95% CI 0.70 to 0.87), leflunomide (0.80, 95% CI
      0.65 to 0.98) or csDMARD combinations (0.77, 95% CI 0.68 to 0.87) reduced the
      risk of bDMARD withdrawal. CONCLUSION: Adalimumab and infliximab monotherapies
      show lower retention rate compared with etanercept. The relatively small number
      of therapeutic courses different from tumour necrosis factor (TNF) inhibitors
      makes more difficult to achieve conclusive results with other biologics.
      Concomitant methotrexate, leflunomide and csDMARDs combination associate with
      longer survival on bDMARD. Our data confirm the effectiveness of the current
      practices in the choice of etanercept as first-line anti-TNF monotherapy and
      strengthen the currently recommended use of bDMARDs in combination with csDMARDs.

PMID- 30206083
TI  - Do statins improve outcomes for patients with non-small cell lung cancer? A
      systematic review and meta-analysis protocol.
AB  - INTRODUCTION: Lung cancer is the most common neoplasm and the leading cause of
      cancer-related death worldwide. Non-small cell lung cancer (NSCLC), accounting
      for 85% of all lung cancer cases, is frequently diagnosed at an advanced and
      metastatic stage. In addition, survival of patients with NSCLC has not improved
      significantly over the recent decades. Statins are used as a cholesterol-lowering
      agent, but recently preclinical and clinical studies have revealed their
      anticancer effects. Thus, this systematic review and meta-analysis aims to
      clarify whether statins improve the prognosis of patients with NSCLC. METHODS AND
      ANALYSIS: We will search MEDLINE (PubMed), EMBASE, Web of Science, the Cochrane
      Central Register of Controlled Trials and ClinicalTrials.gov with no restriction
      on language. Both randomised controlled trials (RCTs) and observational cohort
      studies evaluating the prognostic role of statins in patients with NSCLC will be
      included. The primary outcome will be overall survival, and the secondary
      outcomes will include cancer-specific survival, disease-free survival and cancer
      recurrence. Two assessors will assess the RCTs using the Cochrane Collaboration's
      risk of bias tool and the observational cohort studies according to ROBINS-I.
      Publication bias will be assessed by funnel plot using the STATA software v.13.1.
      ETHICS AND DISSEMINATION: No ethical issues are predicted. This systematic review
      and meta-analysis aims to describe the prognostic effects of statins in patients
      with NSCLC, which would help clinicians to optimise treatment for patients with
      NSCLC. These findings will be published in a peer-reviewed journal and presented
      at national and international conferences. PROSPERO REGISTRATION NUMBER:
      CRD42016047524.

PMID- 30206084
TI  - A mixed-methods study to explore opinions of research translation held by
      researchers working in a Centre of Research Excellence in Australia.
AB  - OBJECTIVE: There is a growing need for researchers to demonstrate impact, which
      is reliant on successful research translation. The Australian National Health and
      Medical Research Council funded a Centre of Research Excellence in Stroke
      Rehabilitation and Brain Recovery (CRE-Stroke) to enhance collaborations between
      researchers conducting different types of stroke rehabilitation research. The
      purpose of this study was to explore opinions about research translation held by
      CRE-Stroke researchers conducting preclinical and clinical research, in terms of
      scope, importance, responsibility and perceived skills and knowledge. DESIGN:
      Mixed-methods study, comprising a paper-based survey and semistructured
      interviews. Interview data were inductively coded and thematically analysed.
      Survey and interview data were compared and synthesised. PARTICIPANTS: 55 (7
      preclinical, 48 clinical) researchers attending a CRE-Stroke research forum
      completed a paper-based survey. Semistructured interviews with 22 CRE-Stroke (5
      preclinical, 17 clinical) researchers were conducted. RESULTS: Research
      translation was described as translating to other research and translating to
      clinical practice and policy. Most researchers (n=54, 98%) reported that research
      translation was important, particularly in terms of generating research impact,
      but the most common sign of project completion reported by researchers (n=7, 100%
      preclinical; n=37, 77% clinical) was publication. Most researchers (preclinical
      n=4, 57%; clinical n=37, 77%) reported having responsibility for translating
      research, but less than half reported having the necessary skills (n=1, 14%
      preclinical; n=17, 35% clinical) and knowledge (n=3, 43% preclinical; n=19, 40%
      clinical). Differing opinions about who should be responsible for translating
      findings to clinical practice were expressed. CONCLUSIONS: Stroke rehabilitation
      researchers appear confident to translate their research via the traditional
      mechanism of publications. To optimise impact, clarity is needed regarding who is
      best placed to translate research findings to clinical practice and policy.
      Education and skills development to apply broader translation processes are
      needed to maximise the use of research at all stages.

PMID- 30206085
TI  - Are noise and air pollution related to the incidence of dementia? A cohort study
      in London, England.
AB  - OBJECTIVE: To investigate whether the incidence of dementia is related to
      residential levels of air and noise pollution in London. DESIGN: Retrospective
      cohort study using primary care data. SETTING: 75 Greater London practices.
      PARTICIPANTS: 130 978 adults aged 50-79 years registered with their general
      practices on 1 January 2005, with no recorded history of dementia or care home
      residence. PRIMARY AND SECONDARY OUTCOME MEASURES: A first recorded diagnosis of
      dementia and, where specified, subgroups of Alzheimer's disease and vascular
      dementia during 2005-2013. The average annual concentrations during 2004 of
      nitrogen dioxide (NO2), particulate matter with a median aerodynamic diameter
      <=2.5 um (PM2.5) and ozone (O3) were estimated at 20*20 m resolution from
      dispersion models. Traffic intensity, distance from major road and night-time
      noise levels (Lnight) were estimated at the postcode level. All exposure measures
      were linked anonymously to clinical data via residential postcode. HRs from Cox
      models were adjusted for age, sex, ethnicity, smoking and body mass index, with
      further adjustments explored for area deprivation and comorbidity. RESULTS: 2181
      subjects (1.7%) received an incident diagnosis of dementia (39% mentioning
      Alzheimer's disease, 29% vascular dementia). There was a positive exposure
      response relationship between dementia and all measures of air pollution except
      O3, which was not readily explained by further adjustment. Adults living in areas
      with the highest fifth of NO2 concentration (>41.5 ug/m3) versus the lowest fifth
      (<31.9 ug/m3) were at a higher risk of dementia (HR=1.40, 95% CI 1.12 to 1.74).
      Increases in dementia risk were also observed with PM2.5, PM2.5 specifically from
      primary traffic sources only and Lnight, but only NO2 and PM2.5 remained
      statistically significant in multipollutant models. Associations were more
      consistent for Alzheimer's disease than vascular dementia. CONCLUSIONS: We have
      found evidence of a positive association between residential levels of air
      pollution across London and being diagnosed with dementia, which is unexplained
      by known confounding factors.

PMID- 30206086
TI  - Can occupational therapist-led home environmental assessment prevent falls in
      older people? A modified cohort randomised controlled trial protocol.
AB  - INTRODUCTION: Falls and fall-related injuries are a serious cause of morbidity
      and cost to society. Environmental hazards are implicated as a major contributor
      to falls among older people. A recent Cochrane review found an environmental
      assessment, undertaken by an occupational therapist, to be an effective approach
      to reducing falls. However, none of the trials included a cost-effectiveness
      evaluation in the UK setting. This protocol describes a large multicentre trial
      investigating the clinical and cost-effectiveness of environmental assessment and
      modification within the home with the aim of preventing falls in older people.
      METHODS AND ANALYSIS: A two-arm, modified cohort randomised controlled trial,
      conducted within England, with 1299 community-dwelling participants aged 65 years
      and above, who are at an increased risk of falls. Participants will be randomised
      2:1 to receive either usual care or home assessment and modification. The primary
      outcome is rate of falls (falls/person/time) over 12 months assessed by monthly
      patient self-report falls calendars. Secondary self-reported outcome measures
      include: the proportion of single and multiple fallers, time to first fall over a
      12-month period, quality of life (EuroQoL EQ-5D-5L) and health service
      utilisation at 4, 8 and 12 months. A nested qualitative study will examine the
      feasibility of providing the intervention and explore barriers, facilitators,
      workload implications and readiness to employ these interventions into routine
      practice. An economic evaluation will assess value for money in terms of cost per
      fall averted. ETHICS AND DISSEMINATION: This study protocol (including the
      original application and subsequent amendments) received a favourable ethical
      opinion from National Health Service West of Scotland REC 3. The trial results
      will be published in peer-reviewed journals and at conference presentations. A
      summary of the findings will be sent to participants. TRIAL REGISTRATION NUMBER:
      ISRCTN22202133; Pre-results.

PMID- 30206087
TI  - Role of cognitive ability in the association between functional health literacy
      and mortality in the Lothian Birth Cohort 1936: a prospective cohort study.
AB  - OBJECTIVES: We investigated the role that childhood and old age cognitive ability
      play in the association between functional health literacy and mortality. DESIGN:
      Prospective cohort study. SETTING: This study used data from the Lothian Birth
      Cohort 1936 (LBC1936) study, which recruited participants living in the Lothian
      region of Scotland when aged 70 years, most of whom had completed an intelligence
      test at age 11 years. PARTICIPANTS: 795 members of the LBC1936 with scores on
      tests of functional health literacy and cognitive ability in childhood and older
      adulthood. PRIMARY AND SECONDARY OUTCOME MEASURES: Participants were followed up
      for 8 years to determine mortality. Time to death in days was used as the primary
      outcome measure. RESULTS: Using Cox regression, higher functional health literacy
      was associated with lower risk of mortality adjusting for age and sex, using the
      Shortened Test of Functional Health Literacy in Adults (HR 0.95, 95% CI 0.92 to
      0.98), the Newest Vital Sign (HR 0.88, 95% CI 0.80 to 0.97) and a functional
      health literacy composite measure (HR 0.77, 95% CI 0.65 to 0.92), but not the
      Rapid Estimate of Adult Literacy in Medicine (HR 0.95, 95% CI 0.90 to 1.01).
      Adjusting for childhood intelligence did not change these associations. When
      additionally adjusting for fluid-type cognitive ability in older age,
      associations between functional health literacy and mortality were attenuated and
      non-significant. CONCLUSIONS: Current fluid ability, but not childhood
      intelligence, attenuated the association between functional health literacy and
      mortality. Functional health literacy measures may, in part, assess fluid-type
      cognitive abilities, and this may account for the association between functional
      health literacy and mortality.

PMID- 30206088
TI  - Design and rationale of a randomised controlled trial comparing apixaban to
      phenprocoumon in patients with atrial fibrillation on chronic haemodialysis: the
      AXADIA-AFNET 8 study.
AB  - INTRODUCTION: Patients with end-stage kidney disease requiring maintenance
      haemodialysis treatment experience a dramatic cardiovascular morbidity and
      mortality. Due to the high atherosclerotic and arteriosclerotic burden and
      profound alterations in haemostasis, they frequently suffer and die from both
      thromboembolic and bleeding events. This is a particular concern in patients on
      haemodialysis with atrial fibrillation (AF). Controlled trials on the optimal
      anticoagulation in patients with AF on haemodialysis are not available. The
      randomised controlled phase IIIb AXADIA-AFNET 8 trial will evaluate the safety
      and efficacy of the factor Xa inhibitor apixaban in patients with AF requiring
      haemodialysis. METHODS AND ANALYSIS: A total of 222 patients will be randomised
      in an open-labelled, 1:1 design to receive either apixaban 2.5 mg twice daily or
      dose-adjusted vitamin K antagonist therapy (target international normalised ratio
      2.0-3.0). All patients will be treated and followed up for a minimum of 6 months
      up to a maximum of 24 months. The primary outcome is major or clinically
      relevant, non-major bleedings or death of any cause. Secondary outcomes include
      stroke, cardiovascular death and other thromboembolic events, thus exploring the
      efficacy of apixaban. The first patient was randomised in June 2017. ETHICS AND
      DISSEMINATION: The study protocol was approved by the Ethical Committee of the
      Landesaertzekammer, Westfalen-Lippe and the Medical Faculty of the University of
      Muenster, Muenster, Germany (reference number: 2016-598 f-A). Written informed
      consent will be obtained from all patients prior to study participation,
      including their consent for long-term follow-up. AXADIA-AFNET 8 is an
      investigator-initiated trial. Sponsor is AFNET, Muenster, Germany. Study findings
      will be disseminated to Bristol-Myers Squibb, Munich, Germany, and Pfizer,
      Berlin, Germany, to the participating centres, at research conferences and in
      peer-reviewed journals. TRIAL REGISTRATION NUMBERS: NCT02933697,Pre-results.

PMID- 30206089
TI  - Strategies to improve adherence to antiretroviral therapy and retention in care
      for people living with HIV in high-income countries: a protocol for an overview
      of systematic reviews.
AB  - INTRODUCTION: While access to antiretroviral therapy (ART) for people living with
      HIV has expanded in recent years, additional efforts are required to support
      adherence to medication and retention in care. Interventions should be applicable
      in real-world settings and amenable to widespread use. The objectives of this
      overview are to identify effective pragmatic interventions that increase
      adherence to ART and retention in care for people living with HIV at high risk
      for suboptimal adherence and retention in high-income countries. METHODS AND
      ANALYSIS: We will conduct an overview of systematic reviews of studies on
      interventions which target improved adherence to medication and retention in care
      among high-risk people living with HIV in high-income countries (men who have sex
      with men, African, Caribbean and black people, sex workers, people who inject
      drugs, indigenous people and other socially marginalised groups). We will search
      the following databases: PubMed, EMBASE (Exerpta Medica Database), CINAHL
      (Cumulative Index to Nursing and Allied Health Literature), PsycINFO, Web of
      Science and the Cochrane Library. We will conduct screening, data extraction and
      assessment of methodological quality of the systematic reviews. Analysis will be
      narrative. Our findings will be interpreted in light of the certainty of the
      evidence, level of pragmatism, setting and population of interest. ETHICS AND
      DISSEMINATION: Only published secondary data will be used in this study, and
      therefore ethics approval is not required. Our findings will be disseminated as
      peer-reviewed manuscripts, conference abstracts and through community activities.
      The findings from this overview will inform a mixed-methods study among people
      living with HIV and health workers in Ontario, Canada.

PMID- 30206091
TI  - Study protocol for a randomised controlled trial of consenting processes and
      their effects on patient decision-making when undergoing spinal injections: the
      Risks In Spinal Consenting for Surgery (RISCS) trial.
AB  - INTRODUCTION: There are major differences between legal and medical approaches to
      informed consent. Medically, consent is obtained prospectively for an intended
      procedure, to inform the patient of choices, risks and benefits, and to manage
      expectations. Legally, consent is reviewed retrospectively, usually following
      unmet expectations and/or the occurrence of complications. Recent legal cases
      relating to clinical negligence define the establishment of causation and breach
      of duty related to informed consent. However, there is no prospective evidence to
      validate the current judicial perspectives on causation and thus clinical
      negligence. The aim of this randomised controlled trial (RCT) is to investigate
      whether variations in consenting processes for the same procedure lead to changes
      in patient decision-making related to consent for that procedure. METHODS AND
      ANALYSIS: The Risks In Spinal Consenting for Surgery trial is a single-centre,
      non-inferiority RCT, where 220 patients, aged over 18 years, receiving an
      elective, day case spinal injection, will be randomised to either a 'legally
      styled' consent form with 55 risks identified in the world literature, or a
      'medically styled' consent form with the 13 serious or most common risks usually
      quoted by reference to specialist society guidelines. Following explanation of
      the medical reasons for considering an injection therapy and consent to the
      trial, participants will be randomly allocated to one of two groups (1:1). The
      patients are then given the opportunity to discuss any concerns relating to the
      procedure and/or risks with a single specialist practitioner. The primary outcome
      will be rates of consent withdrawal due to the risks explained. Secondary
      outcomes include scores from the State-Trait Anxiety Inventory, Visual Analogue
      Scale, EuroQol 5-dimension questionnaire and Oswestry Disability Index. ETHICS
      AND DISSEMINATION: Results will be presented in peer-reviewed journals and at
      international conferences. This study is approved by the Health Research
      Authority: REC 16/SC/0510. TRIAL REGISTRATION NUMBER: ISRCTN67513618; Pre
      results.

PMID- 30206090
TI  - Study protocol for the MEXiletine hydrochloride administration trial: a placebo
      controlled, randomised, double-blind, multicentre, crossover study of its
      efficacy and safety in spinal and bulbar muscular atrophy (MEXPRESS).
AB  - INTRODUCTION: Spinal and bulbar muscular atrophy (SBMA) is a slowly progressive
      neuromuscular disease. Cold exposure often leads to worsening of motor symptoms
      including paresis. Although mexiletine hydrochloride administration has been
      shown to be effective for the treatment of several muscular diseases, its
      effectiveness in SBMA has not been validated to date. The trial will test it as a
      symptomatic drug for cold paresis. This study is the first trial to evaluate the
      efficacy and safety of mexiletine hydrochloride administration in patients with
      SBMA. METHODS AND ANALYSIS: A placebo-controlled, randomised, double-blind,
      multicentre, crossover clinical trial will be conducted to assess the safety and
      efficacy of mexiletine hydrochloride in patients with SBMA. The eligible patients
      will be assigned randomly in a 1:1 ratio to two groups in a double-blind manner.
      Participants will take mexiletine hydrochloride (300 mg/day) or a placebo orally
      three times a day for 4 weeks (period 1). After a 1-week washout period,
      participants will take the other drug for 4 weeks (period 2). The primary
      endpoint is the difference in distal latencies between room temperature and cold
      exposure conditions. ETHICS AND DISSEMINATION: This study will be conducted in
      compliance with the Helsinki Declaration and the Ethical Guidelines for Medical
      and Health Research Involving Human Subjects by the Japanese government and has
      been approved by the ethics committee of Nagoya University Graduate School of
      Medicine, as a central institutional review board, and by each facility. The
      results will be disseminated in peer-reviewed journals and at scientific
      conferences. TRIAL REGISTRATION NUMBER: UMIN000026150; Pre-results.

PMID- 30206092
TI  - Prevalence of respiratory bacterial infections in people with lower respiratory
      tract infections in Africa: the BARIAFRICA systematic review and meta-analysis
      protocol.
AB  - INTRODUCTION: The burden of lower respiratory tract infections (LRTIs) is a
      substantial public health concern. However, the epidemiology of LRTI and its
      bacterial aetiologies are poorly characterised, particularly in the African
      continent. Providing accurate data can help design cost-effective interventions
      to curb the burden of respiratory infections in Africa. Therefore, the aim of
      this systematic review and meta-analysis will be to determine the prevalence of
      respiratory Bacterial Aetiologies in people with low Respiratory tract Infections
      in Africa (BARIAFRICA) and associated factors. METHODS AND ANALYSIS: We will
      search PubMed, EMBASE, Web of Science, African Journals Online, Cumulative Index
      to Nursing and Allied Health Literature, and Global Index Medicus to identify
      studies that reported the prevalence (of enough data to compute this estimate) of
      respiratory bacterial infections in people with LRTIs in Africa from 1 January
      2000 to 31 March 2018, without any linguistic restrictions. Study selection, data
      extraction and risk of bias assessment will be conducted independently by two
      investigators. Heterogeneity will be evaluated using the chi2 test on Cochran's Q
      statistic and quantified with H and I2 statistics. Prevalence will be pooled
      using a random-effect meta-analysis model. Subgroup and meta-regression analyses
      will be used to identify sources of heterogeneity of prevalence estimates. This
      study will be reported according to the guidelines of the Preferred Reporting
      Items for Systematic Reviews and Meta-Analyses. ETHICS AND DISSEMINATION: Since
      this study will be based on published data, it does not require ethical approval.
      This systematic review and meta-analysis is intended to serve as a basis for
      determining the burden of LRTIs, for identifying data gaps and for guiding future
      investigations in Africa. The final report will be published in peer-reviewed
      journals, presented in conferences and submitted to relevant health policy
      makers. PROSPERO REGISTRATION NUMBER: CRD42018092359.

PMID- 30206093
TI  - Features for medically serious suicide attempters who do not have a strong intent
      to die: a cross-sectional study in rural China.
AB  - OBJECTIVE: Previous studies have implied that there were many Chinese suicide
      attempters who did not want to die by suicide. In the current study, we explored
      the factors which were associated with low levels of suicide intent. We also
      examined features for medically serious suicide attempters who do not have a
      strong intent to die in rural china. DESIGN: Cross-sectional study. SETTING: The
      interviews occurred between May 2012 and July 2013 in 13 rural counties in
      Shandong and Hunan provinces, China. PARTICIPANTS: Subjects were 791 medically
      serious suicide attempters whose injury and wounds were so serious they required
      hospitalisation or immediate medical care. RESULTS: The results supported that
      less years of education (beta=-0.11, p=0.037), religious beliefs (beta=1.20,
      p=0.005), living alone (beta=1.92, p=0.017), negative life events (beta=0.29,
      p=0.003), low levels of impulsivity (beta=-0.10, p=0.013) and mental disorders
      (beta=2.82, p<0.001) were associated with higher levels of suicide intent.
      CONCLUSION: Results imply that there are some medically serious suicide
      attempters with a higher education and/or exhibit impulsivity who do not want to
      die by suicide. These findings can inform practice to prevent suicide in rural
      China.

PMID- 30206094
TI  - What evidence is used to underpin the design of strength-based exercise
      interventions evaluated in randomised controlled trials for rheumatoid arthritis?
      A systematic review protocol.
AB  - INTRODUCTION: Healthcare researchers designing strength-based exercise
      interventions must choose an appropriate dose to test before evaluating its
      effect using a definitive/phase-III randomised controlled trial (RCT). Compared
      with early phase testing employed by pharmaceutical trials, it is questionable
      whether exercise-based trials employ the same rigour for establishing tolerated
      dosage. Consequently, it is unclear if participants are initially prescribed
      optimal doses of exercise, which may potentially impact on study outcomes. Using
      trials of strength-based exercise interventions in adults with rheumatoid
      arthritis (RA) as an exemplar, the aims of this review are to (1) identify the
      proportion of RCTs that use phase I/II trials with dose escalation methodology
      for setting prescription parameters, (2) determine type and level of evidence
      used to justify prescription parameters of strength-based exercise interventions
      evaluated by RCTs, (3) explore consistency and applicability of the evidence
      underpinning prescription parameters in RCTs and (4) explore if a relationship
      exists between risk of bias for RCTs evaluating strength-based interventions and
      the level of evidence used to underpin prescription parameters. METHODS AND
      ANALYSIS: Focusing on RCT's evaluating strength-based exercise interventions in
      adults with RA published after 2000, the following databases will be searched:
      Allied and Complementary Medicine Database, Cochrane Central Register of
      Controlled Trials, Cumulative Index to Nursing and Allied Health Literature,
      Excerpta Medica Database, Medline and Physiotherapy Evidence Database. For each
      RCT, we will identify the evidence used to underpin prescription parameters. Both
      trial and underpinning evidence will have key information about the intervention
      extracted using the template for intervention description and replication
      checklist. Risk of bias will be assessed according to Cochrane. Levels of
      evidence will be assessed against the Oxford Centre for Evidence-Based Medicine
      and relationships between RCT and underpinning evidence explored and described
      narratively. Two independent assessors will be involved throughout data selection
      and extraction with recourse to a third reviewer should agreement not be reached.
      ETHICS AND DISSEMINATION: No ethical issues are identified. Dissemination will be
      via publication. PROSPERO REGISTRATION NUMBER: CRD42018090963.

PMID- 30206095
TI  - Singing for people with aphasia (SPA): a protocol for a pilot randomised
      controlled trial of a group singing intervention to improve well-being.
AB  - INTRODUCTION: The singing for people with aphasia (SPA) intervention aims to
      improve quality of life and well-being for people with poststroke aphasia. A
      definitive randomised controlled trial (RCT) is required to assess the clinical
      and cost effectiveness of SPA. The purpose of this pilot study is to assess the
      feasibility of such a definitive trial and inform its design. METHODS AND
      ANALYSIS: A two-group, assessor-blinded, randomised controlled external pilot
      trial with parallel mixed methods process evaluation and economic evaluation.
      Forty-eight participants discharged from clinical speech and language therapy
      will be individually randomised 1:1 to SPA (10 group sessions plus a resource
      booklet) or control (resource booklet only). Outcome assessment at baseline, 3
      and 6 months postrandomisation include: ICEpop CAPability measure for adults,
      Stroke and Aphasia Quality of Life, EQ-5D-5L, modified Reintegration into Normal
      Living Index, Communication Outcome After Stroke, Very Short Version of the
      Minnesota Aphasia Test, Service Receipt Inventory and Care Related Quality of
      Life. Feasibility, acceptability and process outcomes include recruitment and
      retention rates, with measurement burden and trial experiences being explored in
      qualitative interviews (15 participants, 2 music facilitators and 2 music
      champions). Analyses include: descriptive statistics, with 95% CIs where
      appropriate; qualitative themes; intervention fidelity from videos and session
      checklists; rehearsal of health economic analysis. ETHICS AND DISSEMINATION: NHS
      National Research Ethics Service and the Health Research Authority confirmed
      approval in April 2017; recruitment commenced in June 2017. Outputs will include:
      pilot data to inform whether to proceed to a definitive RCT and support a funding
      application; finalised intervention manual for multicentre replication of SPA;
      presentations at conferences, public involvement events; internationally
      recognised peer reviewed journal publications, open access sources and media
      releases. TRIAL REGISTRATION NUMBER: NCT03076736.

PMID- 30206097
TI  - Correction: Missed opportunities for HIV testing among patients newly presenting
      for HIV care at a Swiss university hospital: a retrospective analysis.

PMID- 30206096
TI  - Enhancing self-care adherence in patients with heart failure: a study protocol
      for developing a theory-based behaviour change intervention using the COM-B
      behaviour model (ACHIEVE study).
AB  - INTRODUCTION: Although international guidelines recommend self-care as an
      integral part of routine heart failure management, and despite evidence
      supporting the positive outcomes related to self-care, patients are frequently
      unable to adhere. Self-care can be modified through behaviour change
      interventions (BCIs). However, previous self-care interventions have shown
      limited success in improving adherence to self-care, because they were neither
      theory-based nor well defined, which precludes the identification of underlying
      causal mechanisms as well as reproducibility of the intervention. Thus, our aim
      is to develop an intervention manual that contains theory-based BCIs that are
      well-defined using eight descriptors proposed to describe BCIs in a standardised
      way. METHODS AND ANALYSIS: BCIs will be based on statements of findings derived
      through qualitative meta-summary techniques and a quantitative meta-analysis.
      These reviews will be used to extract factors (target behaviours) associated with
      self-care adherence/non-adherence. Extracted target behaviours will be mapped
      onto the 'Capability, Opportunity, Motivation and Behaviour' (COM-B) model to
      capture the underlying mechanisms involved. To develop approaches for change, the
      'Taxonomy of Behaviour Change Techniques' will be used to allow effective mapping
      of the target behaviours onto established behaviour change techniques. Suggested
      BCIs will then be translated into locally relevant interventions using the
      Normalisation Process Theory to overcome the difficulties of implementing
      theoretically derived interventions into practice. Finally, a consensus
      development method will be employed to fine-tune the content and acceptability of
      the intervention manual to increase the likelihood of successfully piloting and
      implementing future BCIs into the German healthcare system. ETHICS AND
      DISSEMINATION: This study has been reviewed and approved by the Ethics Committee
      of the Medical Faculty of the Heinrich Heine University Dusseldorf, Germany (Ref
      #: 2018-30). The results will be disseminated via peer-reviewed journal
      publications, conference presentations and stakeholder engagement activities.
      TRIAL REGISTRATION NUMBER: DRKS00014855; Pre-results.

PMID- 30206098
TI  - Is a matched unrelated donor search needed for all allogeneic transplant
      candidates?
AB  - Donor availability for allogeneic transplantation remains an important factor in
      determining outcomes of a successful transplant. We examined outcomes of 242
      patients treated over 3 years who had a matched unrelated donor (MUD) search at
      our institution. One hundred sixty patients (66%) had a 10 of 10 MUD identified,
      and 85 (53%) proceeded to MUD transplantation. White patients and those with
      common haplotypes were more likely to have a MUD identified (odds ratio [OR], 7.4
      [P < .0001]; OR, 41.6 [P < .0001]), and were more likely to proceed to
      transplantation with a MUD (OR, 11.2 [P < .0001]; OR, 85.1 [P = .002]). In
      addition, patients who were newly diagnosed/in remission at the time of MUD
      search had a higher probability of receiving a transplant (OR, 2.01 [P = .013])
      and better progression-free survival (PFS; P < .0001). In multivariate analysis
      for patients who received a transplant, donor type did not influence PFS at 3
      years, which was 40% for MUD and 57% for haploidentical transplants, respectively
      (hazard ratio, 1.2 [P = .50]). In conclusion, race, haplotype frequency, and
      disease status at the time of MUD search influence the probability of identifying
      a MUD and receiving a transplant. Patients with a low likelihood of receiving a
      MUD transplant may proceed to a haploidentical transplant as soon as indicated,
      as this approach does not appear to compromise transplant outcomes.

PMID- 30206101
TI  - Phenomenology and its relevance to medical humanities: the example of Hermann
      Schmitz's theory of feelings as half-things.
AB  - One leitmotif that medical humanities shares with phenomenology and most
      contemporary medical ethics is emphasising the importance of appreciating the
      patient as a whole person and not merely as an object. With this also comes a
      focus on marginalisation and invisibility. However, it is not entirely clear what
      exactly patient-centred care means. What both phenomenology and medical
      humanities contribute to a 'more humane health-care encounter' (Goldenberg 2010,
      p 44) is offering not only a first-person perspective, but a dialogue between the
      third-person perspective and evidence-based medicine. Therefore, one main aim of
      medical humanities and phenomenology is to pay attention to the lived body (Leib)
      while adding this to the science of the objective body (Korper). In this study, I
      will discuss this connection through the lens of Hermann Schmitz's phenomenology.
      Finally, in light of this dialogue between phenomenology and medical humanities
      some proposals for medical practice shall be suggested.

PMID- 30206102
TI  - 'Bastard bush': acacia thorn injuries and management.
AB  - This case report outlines the presentation and management of a young soldier who
      sustained a lower limb acacia thorn injury while on exercise in Kenya. The injury
      failed to heal with a subsequent ultrasound scan revealing a large retained thorn
      requiring surgical removal and wash out. From this case, lessons can be learnt
      regarding the management of thorn injuries, which are common in exercising troops
      in Kenya and indeed around the world. The key take-home messages are always
      consider a retained thorn if wounds fail to settle, use ultrasound as the imaging
      modality of choice, always remove identified retained thorns and if antibiotics
      are required use broad-spectrum antibiotics pending culture results.

PMID- 30206100
TI  - Deciphering the differentiation trajectory from hematopoietic stem cells to mast
      cells.
AB  - Hematopoietic stem cells differentiate into all types of blood cells, including
      peripheral tissue-resident mast cells. The early mast cell differentiation takes
      place in the bone marrow, after which the progenitor cells enter the circulation
      and mature once reaching their target organ. Early results from single-cell
      culture experiments and colony-forming assays have produced the classic
      hierarchical tree model of hematopoiesis. The introduction of high-throughput,
      single-cell RNA sequencing is now revolutionizing our understanding of the
      differentiation process, questioning the classic tree-based models. By
      integrating the results from early cell culture experiments with single-cell
      transcriptomics, we present a differentiation landscape model of hematopoiesis
      and discuss it with focus on mast cells. The review also describes how the
      hematologic neoplasm systemic mastocytosis can be used to model human
      hematopoiesis using naturally occurring cell barcoding by means of the common KIT
      D816V mutation.

PMID- 30206099
TI  - A beta1-tubulin-based megakaryocyte maturation reporter system identifies novel
      drugs that promote platelet production.
AB  - During maturation, megakaryocytes (MKs) express beta1-tubulin (TUBB1) and
      rearrange their microtubule components to enlarge, form proplatelets, and
      eventually release platelets. The development of a platform to identify in vitro
      conditions that would efficiently promote MK development could potentially enable
      large-scale platelet production. Here, we show that an immortalized MK cell line
      (imMKCL) genetically modified to express the beta1-tubulin-Venus reporter
      provides a practical system to efficiently monitor the in vitro production of
      platelet-like particles (PLPs). The Venus transgene was inserted downstream of
      the TUBB1 locus in imMKCLs using CRISPR/Cas9, and the expression was visualized
      by Venus fluorescence intensity. This imMKCL reporter line was then used for high
      throughput drug screening. We identified several compounds that significantly
      improved the efficiency of PLP production in vitro under feeder-free conditions
      and showed a significant tendency to recover platelets in vivo in a mouse
      thrombocytopenia model induced by anti-GPIbalpha antibody administration.
      Interestingly, most of these compounds, including a WNT signaling pathway
      inhibitor, Wnt-C59, antagonized the aryl hydrocarbon receptor (AhR) to increase
      PLP production, confirming the crucial role of AhR inhibition in MK maturation.
      Consistently, small interfering RNA treatment against AhR increased the Venus
      intensity and PLP production. TCS 359, an FLT3 inhibitor, significantly increased
      PLP production independently of FLT3 or AhR. This study highlights the usefulness
      of the beta1-tubulin reporter MK line as a useful tool to study the mechanisms
      underlying thrombopoiesis and to identify novel inducers of ex vivo platelet
      production.

PMID- 30206103
TI  - Dispatches from the editor: highlights of the September 2018 issue.

PMID- 30206105
TI  - MAPINS, a highly efficient detection method that identifies insertional mutations
      and complex DNA rearrangements.
AB  - Insertional mutagenesis, in which a piece of exogenous DNA is randomly integrated
      into the genomic DNA of the recipient cell, is a useful method to generate new
      mutants with phenotypes of interest. The unicellular green alga Chlamydomonas
      reinhardtii is an outstanding model for studying many biological processes. We
      developed a new computational algorithm, MAPINS (mapping insertions), to
      efficiently identify insertion sites created by the integration of an APHVIII
      (aminoglycoside 3'-phosphotransferase VIII) cassette that confers paromomycin
      resistance. Using whole-genome sequencing (WGS) data, this method eliminates the
      need for genomic DNA manipulation and retains all the sequencing information
      provided by paired-end sequencing. We experimentally verified 38 insertion sites
      out of 41 sites (93%) identified by MAPINS from 20 paromomycin-resistant strains.
      Using meiotic analysis of 18 of these strains, we identified insertion sites that
      completely cosegregate with paromomycin resistance. In six of the seven strains
      with a mutant phenotype, we demonstrated complete cosegregation of the mutant
      phenotype and the verified insertion site. In addition, we provide direct
      evidence of complex rearrangements of genomic DNA in five strains, three of which
      involve the APHVIII insertion site. We suggest that strains obtained by
      insertional mutagenesis are more complicated than expected from previous analyses
      in Chlamydomonas. To map the locations of some complex insertions, we designed 49
      molecular markers based on differences identified via WGS between wild-type
      strains CC-124 and CC-125. Overall, MAPINS provides a low-cost, efficient method
      to characterize insertional mutants in Chlamydomonas.

PMID- 30206104
TI  - Arabidopsis PIRL6 Is Essential for Male and Female Gametogenesis and Is Regulated
      by Alternative Splicing.
AB  - Plant intracellular Ras-group leucine-rich repeat (LRR) proteins (PIRLs) are
      related to Ras-interacting animal LRR proteins that participate in developmental
      cell signaling. Systematic knockout analysis has implicated some members of the
      Arabidopsis (Arabidopsis thaliana) PIRL family in pollen development. However,
      for PIRL6, no bona fide knockout alleles have been recovered, suggesting that it
      may have an essential function in both male and female gametophytes. To test this
      hypothesis, we investigated PIRL6 expression and induced knockdown by RNA
      interference. Knockdown triggered defects in gametogenesis, resulting in abnormal
      pollen and early developmental arrest in the embryo sac. Consistent with this,
      PIRL6 was expressed in gametophytes: functional transcripts were detected in wild
      type flowers but not in sporocyteless (spl) mutant flowers, which do not produce
      gametophytes. A genomic PIRL6-GFP fusion construct confirmed expression in both
      pollen and the embryo sac. Interestingly, PIRL6 is part of a convergent
      overlapping gene pair, a scenario associated with an increased likelihood of
      alternative splicing. We detected multiple alternative PIRL6 mRNAs in vegetative
      organs and spl mutant flowers, tissues that lacked the functionally spliced
      transcript. cDNA sequencing revealed that all contained intron sequences and
      premature termination codons. These alternative mRNAs accumulated in the nonsense
      mediated decay mutant upf3, indicating that they are normally subjected to
      degradation. Together, these results demonstrate that PIRL6 is required in both
      male and female gametogenesis and suggest that sporophytic expression is
      negatively regulated by unproductive alternative splicing. This
      posttranscriptional mechanism may function to minimize PIRL6 protein expression
      in sporophyte tissues while allowing the overlapping adjacent gene to remain
      widely transcribed.

PMID- 30206107
TI  - Impact of differences in nutritional quality of wingless and winged aphids on
      parasitoid fitness.
AB  - Winged aphids are described as hosts of lesser quality for parasitoids because a
      part of their resources is used to produce wings and associated muscles during
      their development. Host lipid content is particularly important for parasitoid
      larvae as they lack lipogenesis and therefore rely entirely on the host for this
      resource. The goal of this study was to determine to what extent winged and
      wingless aphids differ from a nutritional point of view and whether these
      differences impact parasitoid fitness, notably the lipid content. We analysed the
      energetic budget (proteins, lipids and carbohydrates) of aphids of different ages
      (third instars, fourth instars and adults) according to the morph (winged or
      wingless). We also compared fitness indicators for parasitoids emerging from
      winged and wingless aphids (third and fourth instars). We found that in third
      instars, parasitoids are able to inhibit wing development whereas this is not the
      case in fourth instars. Both winged instars allow the production of heavier and
      fattier parasitoids. The presence of wings in aphids seems to have little effect
      on the fitness of emerging parasitoids and did not modify female choice for
      oviposition. Finally, we demonstrate that Aphidius colemani, used as a biological
      control agent, is able to parasitize wingless as well as winged Myzus persicae,
      at least in the juvenile stages. If the parasitism occurs in third instars, the
      parasitoid will prevent the aphid from flying, which could in turn reduce virus
      transmission.

PMID- 30206106
TI  - Sprague Dawley Rag2-Null Rats Created from Engineered Spermatogonial Stem Cells
      Are Immunodeficient and Permissive to Human Xenografts.
AB  - The rat is the preferred model for toxicology studies, and it offers distinctive
      advantages over the mouse as a preclinical research model including larger sample
      size collection, lower rates of drug clearance, and relative ease of surgical
      manipulation. An immunodeficient rat would allow for larger tumor size
      development, prolonged dosing and drug efficacy studies, and preliminary
      toxicologic testing and pharmacokinetic/pharmacodynamic studies in the same model
      animal. Here, we created an immunodeficient rat with a functional deletion of the
      Recombination Activating Gene 2 (Rag2) gene, using genetically modified
      spermatogonial stem cells (SSC). We targeted the Rag2 gene in rat SSCs with
      TALENs and transplanted these Rag2-deficient SSCs into sterile recipients.
      Offspring were genotyped, and a founder with a 27 bp deletion mutation was
      identified and bred to homozygosity to produce the Sprague-Dawley Rag2 - Rag2
      tm1Hera (SDR) knockout rat. We demonstrated that SDR rat lacks mature B and T
      cells. Furthermore, the SDR rat model was permissive to growth of human
      glioblastoma cell line subcutaneously resulting in successful growth of tumors.
      In addition, a human KRAS-mutant non-small cell lung cancer cell line (H358), a
      patient-derived high-grade serous ovarian cancer cell line (OV81), and a patient
      derived recurrent endometrial cancer cell line (OV185) were transplanted
      subcutaneously to test the ability of the SDR rat to accommodate human xenografts
      from multiple tissue types. All human cancer cell lines showed efficient tumor
      uptake and growth kinetics indicating that the SDR rat is a viable host for a
      range of xenograft studies. Mol Cancer Ther; 17(11); 2481-9. (c)2018 AACR.

PMID- 30206108
TI  - 5-HT2A Receptor Agonist-Induced Hyperthermia Is Induced via Vasoconstriction by
      Peripheral 5-HT2A Receptors and Brown Adipose Tissue Thermogenesis by Peripheral
      Serotonin Loss at a High Ambient Temperature.
AB  - Recreational drugs such as 3,4-methylenedioxymethamphetamine and cocaine induce
      hyperthermia, which is affected by ambient temperature. 2-(4-Bromo-2,5
      dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine (25B-NBOMe), a selective agonist
      of 5-HT2A receptor used as a recreational drug, reportedly induces hyperthermia.
      This study aimed to verify whether 25B-NBOMe induces ambient temperature
      dependent hyperthermia and to clarify its mechanism. Eight-week-old male Sprague
      Dawley rats were administered intraperitoneal injection of 25B-NBOMe at an
      ambient temperature of 23 degrees C or 29 degrees C. 25B-NBOMe administration at
      23 degrees C did not change the core body temperature of the rats, whereas
      administration at 29 degrees C induced significant hyperthermia 30-120 minutes
      postadministration. Tail surface temperature temporarily decreased 30 minutes
      postadministration, indicating heat storage by peripheral vasoconstriction
      despite a high ambient temperature. Because 25B-NBOMe-induced-hyperthermia was
      suppressed by sarpogrelate, but not by destruction of central noradrenaline or
      serotonin neurons, peripheral 5-HT2A receptors were considered contributors to
      the development of hyperthermia at a high ambient temperature, independently from
      central neurons. The temperature of brown adipose tissue (BAT) increased 60-120
      minutes postadministration of 25B-NBOMe at 29 degrees C, indicating
      thermogenesis. Previous studies have reported that peripheral serotonin
      contributes to the inhibition of BAT thermogenesis. Decreased plasma serotonin
      levels were observed at 29 degrees C, and serotonin administration partially
      suppressed 25B-NBOMe-induced hyperthermia at a high ambient temperature,
      suggesting that decreased levels of peripheral serotonin induced BAT
      thermogenesis. Our findings indicate that 25B-NBOMe induces hyperthermia at a
      high ambient temperature via vasoconstriction regulated by 5-HT2A receptors and
      BAT thermogenesis mediated by decreased levels of plasma serotonin. Thus,
      peripheral serotonin plays a partial but important role in thermoregulation.

PMID- 30206109
TI  - Cervical Cancer Screening Every 5 Years OK.
AB  - New cervical cancer screening recommendations from the U.S. Preventive Services
      Task Force offer many women a new option: being screened every 5 years using high
      risk human papillomavirus (HPV) testing. This change reflects new data on HPV
      testing, but screening every 3 years with a Pap test or every 5 years with both
      HPV and Pap tests remain options.

PMID- 30206112
TI  - Better Pairing Propofol Volume With Procedural Needs: A Propofol Waste Reduction
      Quality Improvement Project.
AB  - BACKGROUND AND OBJECTIVES: Propofol facilitates deep sedation without requiring
      intubation and is often used by infusion to maintain sedation. Variability in
      ordering and preparation strategies resulted in significant propofol volumes
      wasted at the conclusion of procedures in our clinic. With drug shortages now
      common, we designed a quality improvement initiative to reduce our propofol
      waste. METHODS: Data collection during the preintervention phase reflected
      current practice trends. Two propofol dosing tables (>=50 or <50 kg) were
      designed to estimate the volume of propofol infusion required for sedations
      spanning 15 to 180 minutes. Nurses prepared propofol infusions as directed by
      these tables. The primary outcome measure was reduction in waste when the
      infusion was prepared by standardized strategy versus usual practice. Balancing
      measures included occurrences of insufficient infusion volume and premature
      awakenings from deep sedation. Waste volumes were plotted and displayed
      chronologically in statistical process control charts for the clinic and
      individual providers. RESULTS: A total of 155 patients received a propofol
      infusion to maintain deep sedation. The preintervention phase included 77
      patients, and the intervention phase included 78 patients. Special cause
      variation was achieved in the intervention phase. Median (interquartile range)
      propofol waste volume per procedure declined from 45.6 mL (24.3-71 mL) to 14.3 mL
      (9.6-19.4 mL), representing a 68% waste reduction. CONCLUSIONS: Using an
      internally derived systematic approach to ordering and preparing a propofol
      infusion, we reduced variability, reduced propofol waste, and created cost
      savings for our organization. This approach is tailorable to other infusions and
      clinical settings.

PMID- 30206110
TI  - The Genetic Landscape and Clonal Evolution of Breast Cancer Resistance to
      Palbociclib plus Fulvestrant in the PALOMA-3 Trial.
AB  - CDK4/6 inhibition with endocrine therapy is now a standard of care for advanced
      estrogen receptor-positive breast cancer. Mechanisms of CDK4/6 inhibitor
      resistance have been described preclinically, with limited evidence from clinical
      samples. We conducted paired baseline and end-of-treatment circulating tumor DNA
      sequencing from 195 patients in the PALOMA-3 randomized phase III trial of
      palbociclib plus fulvestrant versus placebo plus fulvestrant. We show that clonal
      evolution occurs frequently during treatment, reflecting substantial subclonal
      complexity in breast cancer that has progressed after prior endocrine therapy.
      RB1 mutations emerged only in the palbociclib plus fulvestrant arm and in a
      minority of patients (6/127, 4.7%, P = 0.041). New driver mutations emerged in
      PIK3CA (P = 0.00069) and ESR1 after treatment in both arms, in particular ESR1
      Y537S (P = 0.0037). Evolution of driver gene mutations was uncommon in patients
      progressing early on palbociclib plus fulvestrant but common in patients
      progressing later on treatment. These findings inform future treatment strategies
      to address resistance to palbociclib plus fulvestrant.Significance: Acquired
      mutations from fulvestrant are a major driver of resistance to fulvestrant and
      palbociclib combination therapy. ESR1 Y537S mutation promotes resistance to
      fulvestrant. Clonal evolution results in frequent acquisition of driver mutations
      in patients progressing late on therapy, which suggests that early and late
      progression have distinct mechanisms of resistance. Cancer Discov; 8(11); 1390
      403. (c)2018 AACR. See related commentary by Schiff and Jeselsohn, p. 1352 This
      article is highlighted in the In This Issue feature, p. 1333.

PMID- 30206111
TI  - The Natural Order of Time: The Power of Statistical Process Control in Quality
      Improvement Reporting.

PMID- 30206113
TI  - David Oliver: Government's approach to alcohol harm is incoherent.

PMID- 30206114
TI  - Introduction to a How I Treat series on sickle cell disease and thalassemia.

PMID- 30206117
TI  - How I manage medical complications of beta-thalassemia in adults.
AB  - The complex pathophysiology in beta-thalassemia can translate to multiple
      morbidities that affect every organ system. Improved survival due to advances in
      management means that patients are exposed to the harmful effects of ineffective
      erythropoiesis, anemia, and iron overload for a longer duration, and we started
      seeing new or more frequent complications in adult compared with younger
      patients. In this article, we highlight particular aspects of managing adult
      patients with beta-thalassemia, using our own experience in treating such
      patients. We cover both transfusion-dependent and nontransfusion-dependent forms
      of the disease and tackle specific morbidities of highest interest.

PMID- 30206115
TI  - How I treat hypoxia in adults with hemoglobinopathies and hemolytic disorders.
AB  - Hemoglobinopathies are caused by genetic mutations that result in abnormal
      hemoglobin molecules, resulting in hemolytic anemia. Chronic complications
      involving the lung parenchyma, vasculature, and cardiac function in
      hemoglobinopathies result in impaired gas exchange, resulting in tissue hypoxia.
      Hypoxia is defined as the deficiency in the amount of oxygen reaching the tissues
      of the body and is prevalent in patients with hemoglobinopathies, and its cause
      is often multifactorial. Chronic hypoxia in hemoglobinopathies is often a sign of
      disease severity and is associated with increased morbidity and mortality.
      Therefore, a thorough understanding of the pathophysiology of hypoxia in these
      disease processes is important in order to appropriately treat the underlying
      cause and prevent complications. In this article, we discuss management of
      hypoxia based on three different cases: sickle cell disease, beta-thalassemia,
      and hereditary spherocytosis. These cases are used to review the current
      understanding of the disease pathophysiology, demonstrate the importance of a
      thorough clinical history and physical examination, explore diagnostic pathways,
      and review the current management.

PMID- 30206116
TI  - How I treat the older adult with sickle cell disease.
AB  - With increasing survival, cumulative complications of sickle cell disease (SCD),
      which develop insidiously over time, are becoming more apparent and common in
      older patients, particularly those in their fifth decade and beyond. The older
      patient is also more likely to develop other age-related nonsickle conditions
      that interact and add to the disease morbidity. A common misconception is that
      any symptom in a SCD patient is attributable to their SCD and this may lead to
      delays in diagnosis and appropriate intervention. We recommend regular
      comprehensive reviews and monitoring for early signs of organ damage and a low
      threshold for the use of hydroxyurea and blood transfusions as preventative
      measures for end-organ disease. Treatable comorbidities and acute deterioration
      should be managed aggressively. Although the primary goal in management of the
      older adult with SCD is improving anemia and minimizing organ damage, the time
      has come for us to be more proactive in considering curative therapies previously
      offered to the younger patient. Curative or experimental interventions should be
      discussed early, before complications render the patients ineligible for these
      treatments.

PMID- 30206119
TI  - Picomolar zinc binding modulates formation of Bcl10-nucleating assemblies of the
      caspase recruitment domain (CARD) of CARD9.
AB  - The caspase recruitment domain-containing protein 9 (CARD9)-B-cell
      lymphoma/leukemia 10 (Bcl10) signaling axis is activated in myeloid cells during
      the innate immune response to a variety of diverse pathogens. This signaling
      pathway requires a critical caspase recruitment domain (CARD)-CARD interaction
      between CARD9 and Bcl10 that promotes downstream activation of factors, including
      NF-kappaB and the mitogen-activated protein kinase (MAPK) p38. Despite these
      insights, CARD9 remains structurally uncharacterized, and little mechanistic
      understanding of its regulation exists. We unexpectedly found here that the CARD
      in CARD9 binds to Zn2+ with picomolar affinity-a concentration comparable with
      the levels of readily accessible Zn2+ in the cytosol. NMR solution structures of
      the CARD9-CARD in the apo and Zn2+-bound states revealed that Zn2+ has little
      effect on the ground-state structure of the CARD; yet the stability of the domain
      increased considerably upon Zn2+ binding, with a concomitant reduction in
      conformational flexibility. Moreover, Zn2+ binding inhibited polymerization of
      the CARD9-CARD into helical assemblies. Here, we also present a 20-A resolution
      negative-stain EM (NS-EM) structure of these filamentous assemblies and show that
      they adopt a similar helical symmetry as reported previously for filaments of the
      Bcl10 CARD. Using both bulk assays and direct NS-EM visualization, we further
      show that the CARD9-CARD assemblies can directly template and thereby nucleate
      Bcl10 polymerization, a capacity considered critical to propagation of the CARD9
      Bcl10 signaling cascade. Our findings indicate that CARD9 is a potential target
      of Zn2+-mediated signaling that affects Bcl10 polymerization in innate immune
      responses.

PMID- 30206118
TI  - The CcmC-CcmE interaction during cytochrome c maturation by System I is driven by
      protein-protein and not protein-heme contacts.
AB  - Cytochromes c are ubiquitous proteins, essential for life in most organisms.
      Their distinctive characteristic is the covalent attachment of heme to their
      polypeptide chain. This post-translational modification is performed by a
      dedicated protein system, which in many Gram-negative bacteria and plant
      mitochondria is a nine-protein apparatus (CcmA-I) called System I. Despite
      decades of study, mechanistic understanding of the protein-protein interactions
      in this highly complex maturation machinery is still lacking. Here, we focused on
      the interaction of CcmC, the protein that sources the heme cofactor, with CcmE,
      the pivotal component of System I responsible for the transfer of the heme to the
      apocytochrome. Using in silico analyses, we identified a putative interaction
      site between these two proteins (residues Asp47, Gln50, and Arg55 on CcmC; Arg73,
      Asp101, and Glu105 on CcmE), and we validated our findings by in vivo experiments
      in Escherichia coli Moreover, employing NMR spectroscopy, we examined whether a
      heme-binding site on CcmE contributes to this interaction and found that CcmC and
      CcmE associate via protein-protein rather than protein-heme contacts. The
      combination of in vivo site-directed mutagenesis studies and high-resolution
      structural techniques enabled us to determine at the residue level the mechanism
      for the formation of one of the key protein complexes for cytochrome c maturation
      by System I.

PMID- 30206120
TI  - Structural analyses of 4-phosphate adaptor protein 2 yield mechanistic insights
      into sphingolipid recognition by the glycolipid transfer protein family.
AB  - The glycolipid transfer protein (GLTP) fold defines a superfamily of eukaryotic
      proteins that selectively transport sphingolipids (SLs) between membranes.
      However, the mechanisms determining the protein selectivity for specific
      glycosphingolipids (GSLs) are unclear. Here, we report the crystal structure of
      the GLTP homology (GLTPH) domain of human 4-phosphate adaptor protein 2 (FAPP2)
      bound with N-oleoyl-galactosylceramide. Using this domain, FAPP2 transports
      glucosylceramide from its cis-Golgi synthesis site to the trans-Golgi for
      conversion into complex GSLs. The FAPP2-GLTPH structure revealed an element,
      termed the ID loop, that controls specificity in the GLTP family. We found that,
      in accordance with FAPP2 preference for simple GSLs, the ID loop protrudes from
      behind the SL headgroup-recognition center to mitigate binding by complex GSLs.
      Mutational analyses including GLTP and FAPP2 chimeras with swapped ID loops
      supported the proposed restrictive role of the FAPP2 ID loop in GSL selectivity.
      Comparative analysis revealed distinctly designed ID loops in each GLTP family
      member. This analysis also disclosed a conserved H-bond triplet that "clasps"
      both ID-loop ends together to promote structural autonomy and rigidity. The
      findings indicated that various ID loops work in concert with conserved
      recognition centers to create different specificities among family members. We
      also observed four bulky, conserved hydrophobic residues involved in "sensor
      like" interactions with lipid chains in protein hydrophobic pockets and FF motifs
      in GLTP and FAPP2, well-positioned to provide acyl chain-dependent SL selectivity
      for the hydrophobic pockets. In summary, our study provides mechanistic insights
      into sphingolipid recognition by the GLTP fold and uncovers the elements involved
      in this recognition.

PMID- 30206121
TI  - A functional study of all 40 Caenorhabditis elegans insulin-like peptides.
AB  - The human genome encodes 10 insulin-like genes, whereas the Caenorhabditis
      elegans genome remarkably encodes 40 insulin-like genes. Knockout strategies to
      determine the roles of all the insulin/insulin-like peptide ligands (INS) in C.
      elegans has been challenging due to functional redundancy. Here, we individually
      overexpressed each of the 40 ins genes pan-neuronally, and monitored multiple
      phenotypes including: L1 arrest life span, neuroblast divisions under L1 arrest,
      dauer formation, and fat accumulation, as readouts to characterize the functions
      of each INS in vivo Of the 40 INS peptides, we found functions for 35 INS
      peptides and functionally categorized each as agonists, antagonists, or of
      pleiotropic function. In particular, we found that 9 of 16 agonistic INS peptides
      shortened L1 arrest life span and promoted neuroblast divisions during L1 arrest.
      Our study revealed that a subset of beta-class INS peptides that contain a
      distinct F peptide sequence are agonists. Our work is the first to categorize the
      structures of INS peptides and relate these structures to the functions of all 40
      INS peptides in vivo Our findings will promote the study of insulin function on
      development, metabolism, and aging-related diseases.

PMID- 30206123
TI  - Conformational heterogeneity of the allosteric drug and metabolite (ADaM) site in
      AMP-activated protein kinase (AMPK).
AB  - AMP-activated protein kinase (AMPK) is a master regulator of energy homeostasis
      and a promising drug target for managing metabolic diseases such as type 2
      diabetes. Many pharmacological AMPK activators, and possibly unidentified
      physiological metabolites, bind to the allosteric drug and metabolite (ADaM) site
      at the interface between the kinase domain (KD) in the alpha-subunit and the
      carbohydrate-binding module (CBM) in the beta-subunit. Here, using double
      electron-electron resonance (DEER) spectroscopy, we demonstrate that the CBM-KD
      interaction is partially dissociated and the interface highly disordered in the
      absence of pharmacological ADaM site activators as inferred from a low depth of
      modulation and broad DEER distance distributions. ADaM site ligands such as 991,
      and to a lesser degree phosphorylation, stabilize the KD-CBM association and
      strikingly reduce conformational heterogeneity in the ADaM site. Our findings
      that the ADaM site, formed by the KD-CBM interaction, can be modulated by diverse
      ligands and by phosphorylation suggest that it may function as a hub for
      integrating regulatory signals.

PMID- 30206122
TI  - Oxidation of cysteine 117 stimulates constitutive activation of the type Ialpha
      cGMP-dependent protein kinase.
AB  - The type I cGMP-dependent protein kinase (PKG I) is an essential regulator of
      vascular tone. It has been demonstrated that the type Ialpha isoform can be
      constitutively activated by oxidizing conditions. However, the amino acid
      residues implicated in this phenomenon are not fully elucidated. To investigate
      the molecular basis for this mechanism, we studied the effects of oxidation using
      recombinant WT, truncated, and mutant constructs of PKG I. Using an in vitro
      assay, we observed that oxidation with hydrogen peroxide (H2O2) resulted in
      constitutive, cGMP-independent activation of PKG Ialpha. PKG Ialpha C42S and a
      truncation construct that does not contain Cys-42 (Delta53) were both
      constitutively activated by H2O2 In contrast, oxidation of PKG Ialpha C117S
      maintained its cGMP-dependent activation characteristics, although oxidized PKG
      Ialpha C195S did not. To corroborate these results, we also tested the effects of
      our constructs on the PKG Ialpha-specific substrate, the large conductance
      potassium channel (KCa 1.1). Application of WT PKG Ialpha activated by either
      cGMP or H2O2 increased the open probabilities of the channel. Neither cGMP nor
      H2O2 activation of PKG Ialpha C42S significantly increased channel open
      probabilities. Moreover, cGMP-stimulated PKG Ialpha C117S increased KCa 1.1
      activity, but this effect was not observed under oxidizing conditions. Finally,
      we observed that PKG Ialpha C42S caused channel flickers, indicating dramatically
      altered KCa 1.1 channel characteristics compared with channels exposed to WT PKG
      Ialpha. Cumulatively, these results indicate that constitutive activation of PKG
      Ialpha proceeds through oxidation of Cys-117 and further suggest that the
      formation of a sulfur acid is necessary for this phenotype.

PMID- 30206126
TI  - Outcome of Critically Ill Subjects With Tuberculosis: Systematic Review and Meta
      Analysis.
AB  - BACKGROUND: The outcomes of patients with tuberculosis admitted to an ICU remain
      undetermined. Herein, we reviewed the literature to describe the mortality of
      subjects with tuberculosis who are critically ill, and explore the effect of
      glucocorticoids on survival. METHODS: A systematic review of medical literature
      databases was performed for studies that describe the outcome of subjects with
      tuberculosis who required ICU admission. We calculated the proportion of
      hospitalized subjects with tuberculosis who required ICU admission. Pooled
      estimates of ICU and hospital mortality, and tuberculosis-related ARDS were
      calculated. We also studied the effect of systemic glucocorticoids on survival of
      subjects with tuberculosis who were critically ill. RESULTS: A total of 35
      studies (N = 1,815) were included. The pooled proportion of hospitalized subjects
      with tuberculosis who required ICU admission was 3.4% (95% CI 1.6-5.7%). The
      pooled ICU and hospital mortality was 48% (95% CI 41-55%) and 54% (95% CI 46
      62%), respectively. Tuberculosis-related ARDS was associated with higher odds
      (odds ratio 3.88, 95% CI 1.73-8.72) of death. The use of glucocorticoids was not
      related to an improvement in survival (odds ratio 0.65, 95% CI 0.27-1.57).
      CONCLUSIONS: Tuberculosis is a rare cause of ICU admission but is associated with
      high mortality. Tuberculosis-related ARDS is also associated with lower survival.
      The role of glucocorticoids in patients with tuberculosis who are critically ill
      remains unclear and needs further evaluation.

PMID- 30206125
TI  - Approaches to Cough Peak Flow Measurement With Duchenne Muscular Dystrophy.
AB  - BACKGROUND: Manually-assisted coughing and mechanical insufflation-exsufflation
      (MI-E) are commonly used in patients with Duchenne muscular dystrophy (DMD). Few
      studies have compared cough peak flow (CPF) with manually-assisted coughing to
      other methods, such as MI-E + manually-assisted coughing. In addition, few
      studies have reported the reliability of the measured CPF values. This study
      aimed to compare CPF with different cough-assistance methods and to examine the
      reliability of CPF data. METHODS: The study included 12 subjects with DMD (mean
      age, 34 +/- 8 y). CPF, CPF + manually-assisted coughing (assisted CPF), maximum
      insufflation capacity (MIC) + CPF (MIC-CPF), MIC + manually-assisted coughing
      (MIC+assisted CPF), MI-E (MI-E-CPF), and MI-E + assisted CPF were measured. A
      spirometer was used to compare CPF measurements obtained with each of the cough
      assist techniques. The reliability of the measured CPF values was analyzed using
      Bland-Altman analysis. RESULTS: CPF was 59 +/- 34 L/min, assisted CPF was 113 +/-
      32 L/min, MIC-CPF was 170 +/- 30 L/min, MIC+assisted CPF was 224 +/- 62 L/min, MI
      E-CPF was 199 +/- 40 L/min, and MI-E + assisted CPF was 240 +/- 38 L/min. A fixed
      and proportional bias was found in the CPF measurements made with the peak flow
      meter and the spirometer. The average 95% CI in the difference between peak flow
      meter, MI-E, and CPF obtained using the spirometer were -7.45 to -1.95 and -1.45
      to 4.95, respectively. Test for correlation was r = 0.54 (P < .001) for CPF (peak
      flow meter) and CPF (spirometer) and r = 0.17 (P = .17) in CPF (MI-E) and CPF
      (spirometer), respectively. CONCLUSION: MI-E + assisted CPF was the highest. The
      CPF measured with the peak flow meter suggested underestimation.

PMID- 30206124
TI  - Development of an allosteric inhibitor class blocking RNA elongation by the
      respiratory syncytial virus polymerase complex.
AB  - Respiratory syncytial virus (RSV) represents a significant health threat to
      infants and to elderly or immunocompromised individuals. There are currently no
      vaccines available to prevent RSV infections, and disease management is largely
      limited to supportive care, making the identification and development of
      effective antiviral therapeutics against RSV a priority. To identify effective
      chemical scaffolds for managing RSV disease, we conducted a high-throughput anti
      RSV screen of a 57,000-compound library. We identified a hit compound that
      specifically blocked activity of the RSV RNA-dependent RNA polymerase (RdRp)
      complex, initially with moderate low-micromolar potency. Mechanistic
      characterization in an in vitro RSV RdRp assay indicated that representatives of
      this compound class block elongation of RSV RNA products after initial extension
      by up to three nucleotides. Synthetic hit-to-lead exploration yielded an
      informative 3D quantitative structure-activity relationship (3D-QSAR) model and
      resulted in analogs with more than 20-fold improved potency and selectivity
      indices (SIs) of >1,000. However, first-generation leads exhibited limited water
      solubility and poor metabolic stability. A second optimization strategy informed
      by the 3D-QSAR model combined with in silico pharmacokinetics (PK) predictions
      yielded an advanced lead, AVG-233, that demonstrated nanomolar activity against
      both laboratory-adapted RSV strains and clinical RSV isolates. This anti-RSV
      activity extended to infection of established cell lines and primary human airway
      cells. PK profiling in mice revealed 34% oral bioavailability of AVG-233 and
      sustained high drug levels in the circulation after a single oral dose of 20
      mg/kg. This promising first-in-class lead warrants further development as an anti
      RSV drug.

PMID- 30206127
TI  - Evaluating Endotracheal Tube Depth in Infants Weighing Less Than 1 Kilogram.
AB  - BACKGROUND: Endotracheal tube (ETT) depth in premature infants is of critical
      importance because potentially life-threatening adverse events can occur if the
      tube is malpositioned. Analysis of current data indicates that the accuracy of
      current resuscitation guidelines for infants <1 kg is poor. We hypothesized that
      a weight-based formula that is used clinically in our institution would
      accurately predict appropriate ETT placement in infants weighing < 1 kg. METHODS:
      The medical records, from July 2013 to November 2016, of all infants < 1 kg who
      were intubated were retrospectively reviewed and included. The 2 formulas
      utilized were the Duke formulas 5.5 cm + 1 cm/kg for infants 500-999 g or 5.0 + 1
      cm/kg for infants <500 g. The appropriate ETT position was defined as the tip of
      the ETT below the thoracic inlet and above the carina, at approximately thoracic
      vertebrae 2 or 3 on an initial chest radiograph. The formula was defined as being
      accurate if the documented ETT depth was within 0.2 cm of the predicted depth.
      Post hoc analysis of current resuscitation guidelines (6 cm plus the weight of
      the infant in kg) was performed after the Duke formula performed worse than
      expected. RESULTS: A total of 131 subjects (mean +/- gestational age, 26 +/- 1.8
      wk; mean +/- weight, 729 +/- 140 g) were included. The documented depth was
      accurately predicted by the Duke formula for 47% of the subjects, with 69% of the
      ETTs appropriately positioned as seen on a chest radiograph. Sensitivity was
      46.6%, specificity was 53.6%, positive predictive value was 68.8% and negative
      predictive value was 31.4% for the Duke formula. Post hoc analysis current
      resuscitation guidelines found that the documented depth was accurately predicted
      for 23% infants, with 70% of these appropriately positioned ETTs. CONCLUSIONS:
      Our weight-based, institutional formula had a low sensitivity for predicting
      proper ETT depth. Weight-based formulas may have clinical utility; however,
      analysis of current data did not support use in infants < 1 kg. Rapid radiologic
      assessment of ETT placement is required for this patient population.

PMID- 30206128
TI  - Monitoring Cough Effectiveness and Use of Airway Clearance Strategies: A Canadian
      and UK Survey.
AB  - BACKGROUND: Regular monitoring combined with early and appropriate use of airway
      clearance can reduce unplanned hospital admissions for patients with
      neuromuscular disease (NMD) and spinal cord injury (SCI). We aimed to describe
      and compare knowledge of guidelines, monitoring of cough effectiveness, clinician
      prescription/provision of airway clearance strategies, and service provision
      constraints in the United Kingdom and Canada. METHODS: This was a cross-sectional
      survey of clinicians affiliated with NMD and SCI clinics in Canada, 2016
      attendees at the Home Mechanical Ventilation Conference in the United Kingdom,
      and United Kingdom physiotherapist networks. RESULTS: We received 155 surveys (92
      from Canada; 63 from the United Kingdom). More UK respondents (76%) were aware of
      airway clearance guidelines than Canadian (56%) respondents (P = .02). Routine
      assessment of cough effectiveness was reported by more UK respondents (59%) than
      Canadian (42%) respondents (P = .044). Cough peak flow (CPF) was the most common
      method used in both countries, although it was more commonly used in the UK (96%)
      than in Canada (81%, P = .02). Fewer Canadian respondents reported using CPF
      before initiation of airway clearance (81% vs 94%, P = .046), and fewer Canadian
      respondents showed results to patients for technique feedback (76% vs 97%, P =
      .007). Similar participant numbers reported using CPF after initiation to ensure
      adequate technique (73% vs 72%, P = .92). Mechanical insufflation-exsufflation
      (MI-E) + lung volume recruitment (LVR) + manually assisted cough when CPF <= 270
      L/min was most routinely recommended (41% overall). Monotherapy was infrequent
      (LVR 15%, manually assisted cough 7%, and MI-E 4%). More Canadians identified
      constraints on service provision, specifically insufficient public funding for
      equipment (68% vs 39%, P = .002) and inadequate community workers' knowledge (56%
      vs 34%, P = .002). Funding for community support was a common constraint in both
      countries (49% vs 42%). CONCLUSIONS: The somewhat variable cough effectiveness
      monitoring and airway clearance practices identified in this survey confirm the
      need for further work on knowledge translation related to guideline
      recommendations and the need to address common constraints to optimal service
      delivery.

PMID- 30206129
TI  - Physiotherapy and Weaning From Prolonged Mechanical Ventilation.
AB  - BACKGROUND: Patients undergoing prolonged mechanical ventilation represent up to
      15% of all patients requiring weaning from mechanical ventilation. Although
      recent guidelines have recommended including physiotherapy early during
      mechanical ventilation to speed the process of weaning, only indirect evidence
      supporting the use of physiotherapy is available for patients receiving prolonged
      mechanical ventilation. The aim of our study was to evaluate the effects of a
      physiotherapy program in subjects requiring prolonged mechanical ventilation and
      the correlates of successful weaning. METHODS: A retrospective analysis was
      performed on 1,313 consecutive patients admitted to a weaning unit over a 15-y
      period to be liberated from prolonged mechanical ventilation. Subjects underwent
      a program of intensive physiotherapy organized in 4 incremental steps (1-4) and
      were analyzed according to the steps achieved (> 2 steps or <= 2 steps). The rate
      of successful weaning was recorded, and possible predictors were considered. The
      15-y period of observation was divided into 3 consecutive 5-y intervals. RESULTS:
      Out of 560 subjects undergoing final analysis, 349 (62.3%) were successfully
      weaned. The weaning success rate was significantly greater in subjects attaining
      > 2 steps than in subjects who attained <= 2 steps (72.1% vs 55.9%, respectively,
      odds ratio = 2.04, 95% CI = 1.42-2.96, P < .001). Stepwise logistic regression
      analysis showed that achievement of > 2 physiotherapy steps was the main
      predictor of successful weaning (odds ratio = 2.17, 95% CI = 1.48-3.23, P <
      .001). Underlying disease was also a predictor of successful weaning. The overall
      rate of successful weaning decreased, and the median duration of weaning
      increased, during the period of observation. CONCLUSIONS: Our data support the
      inclusion of physiotherapy in the management of patients requiring prolonged
      mechanical ventilation.

PMID- 30206130
TI  - Effect of High-Flow Nasal Cannula on Thoraco-Abdominal Synchrony in Pediatric
      Subjects After Cardiac Surgery.
AB  - BACKGROUND: We previously reported the effects of high-flow nasal cannula (HFNC)
      oxygen therapy on thoraco-abdominal synchrony. This study was designed to clarify
      the effect of HFNC on thoraco-abdominal synchrony in pediatric subjects after
      cardiac surgery and to investigate HFNC optimal flow in this population. METHODS:
      Thoraco-abdominal synchrony was evaluated with respiratory inductive
      plethysmography. After extubation, we delivered oxygen via face mask for 30 min
      to subjects with mild to moderate respiratory failure. Each subject then randomly
      received either 1 or 2 L/kg/min via HFNC for 30 min, followed by the other flow
      level via HFNC for 30 min. After HFNC, face mask delivery was resumed. Rib cage
      and abdominal movement were converted into volumes and 2 quantitative indexes:
      maximum compartmental amplitude/tidal volume (VT) ratio and phase angle. RESULTS:
      Ten subjects of median (interquartile range) age 7 (6-14) months and weighing 6.5
      (5.3-8.8) kg were enrolled. Compared with the first delivery via face mask,
      breathing frequency, maximum compartmental amplitude/VT, phase angle, and minute
      volume significantly decreased at 2 L/kg/min (P < .05 for all) but not at 1
      L/kg/min. PaCO2 did not differ among oxygen therapies. None of the measured
      variables differed between first and second face mask periods. CONCLUSIONS: After
      cardiac surgery, HFNC oxygen therapy at 2 L/kg/min improved thoraco-abdominal
      synchrony and decreased breathing frequency in pediatric subjects.

PMID- 30206131
TI  - Peak Oxygen Uptake and Mortality in Cystic Fibrosis: Systematic Review and Meta
      Analysis.
AB  - BACKGROUND: Aerobic fitness, as measured by peak oxygen uptake (VO2 peak),
      correlates with survival in children and adults with cystic fibrosis (CF). We
      sought to evaluate the effects of VO2 peak on mortality rates in subjects with
      CF. METHODS: An online search in PubMed, Embase, LILACS, and SciELO databases was
      conducted, and cohort studies that assessed mortality rates after oxygen
      absorption measurements during a maximal exercise test were included. Data were
      extracted independently by 2 reviewers. The quality analysis of the selected
      articles was performed using the Newcastle-Ottawa scale. The main outcome
      evaluated was the mortality of subjects with CF. Whenever possible, and if
      appropriate, a random effect meta-analysis was performed. RESULTS: Six cohort
      studies were included in this systematic review including 551 subjects. Five
      studies were classified with high methodological quality. Two analyses were
      carried out to evaluate the influence of VO2 peak on mortality. Total difference
      standardized mean between VO2 peak averages in the survival or non-survival
      groups was -0.606 (95% CI = -0.993 to -0.219, P = .002). In addition, subjects
      with a lower VO2 peak had a significantly higher mortality risk (relative risk
      4.896, 95% CI = 1.086 to 22.072, P = .039) in an 8-y follow-up period.
      CONCLUSION: Low levels of peak oxygen uptake are associated with an increase of
      4.9 in the risk of mortality in subjects with CF. This indicates that VO2 could
      be an important follow-up variable to measure, in addition to FEV1.

PMID- 30206132
TI  - Novel and classical renal biomarkers as evidence for the nephroprotective effect
      of Carica papaya leaf extract.
AB  - The present study is aimed at utilization of novel and classical kidney function
      biomarkers to evaluate the nephroprotective potential of Carica papaya leaf
      extract (CPLE) in gentamicin nephrotoxicity model in albino rats. The used
      classical biomarkers were urea and creatinine; while the new biomarkers were
      Kidney injury molecule-1 (KIM-1) and Clusterin. Forty-five male albino rats were
      assigned into five groups and subjected to different treatments for nine
      consecutive days (vehicles; gentamicin, 100 mg/kg, subcutaneously; ascorbic acid,
      200 mg/kg, orally; CPLE, 150 and 300 mg/kg b wt., orally). Three rats/group were
      killed on days 3, 6, and 9 for blood and tissue samples for renal and oxidation
      markers. Gentamicin resulted in significant increase in urea and creatinine only
      by the end of the experimental course; while the novel biomarkers were evident as
      early as 3 days upon gentamicin injection. When concurrently administered with
      gentamicin, CPLE significantly protected kidney tissues against gentamicin
      nephrotoxic effects indicated by decrement of both the novel and the classical
      standard biomarkers, in a dose-dependent manner. CPLE-mediated protection was
      attributed to its antioxidant potential indicated by significant inhibition of
      malondialdehyde (MDA) levels in both serum and kidney homogenates. The results
      were further supported by histopathological examination that revealed
      considerable amelioration of the pathological microscopic alterations induced by
      repeated gentamicin injection. Phytochemical analysis of CPLE indicated presence
      of tannins and flavonoids. These data may suggest CPLE, based on improvement of
      both classical and novel renal markers, as a highly potent nephroprotective and
      antioxidant from natural source that could be a good remedy in conditions
      associated with renal disorders.

PMID- 30206135
TI  - Phosphatidylinositol 4-phosphate is a major source of GPCR-stimulated
      phosphoinositide production.
AB  - Phospholipase C (PLC) enzymes hydrolyze the plasma membrane (PM) lipid
      phosphatidylinositol 4,5-bisphosphate (PI4,5P2) to generate the second messengers
      inositol trisphosphate (IP3) and diacylglycerol (DAG) in response to receptor
      activation in almost all mammalian cells. We previously found that stimulation of
      G protein-coupled receptors (GPCRs) in cardiac cells leads to the PLC-dependent
      hydrolysis of phosphatidylinositol 4-phosphate (PI4P) at the Golgi, a process
      required for the activation of nuclear protein kinase D (PKD) during cardiac
      hypertrophy. We hypothesized that GPCR-stimulated PLC activation leading to
      direct PI4P hydrolysis may be a general mechanism for DAG production. We measured
      GPCR activation-dependent changes in PM and Golgi PI4P pools in various cells
      using GFP-based detection of PI4P. Stimulation with various agonists caused a
      time-dependent reduction in PI4P-associated, but not PI4,5P2-associated,
      fluorescence at the Golgi and PM. Targeted depletion of PI4,5P2 from the PM
      before GPCR stimulation had no effect on the depletion of PM or Golgi PI4P, total
      inositol phosphate (IP) production, or PKD activation. In contrast, acute
      depletion of PI4P specifically at the PM completely blocked the GPCR-dependent
      production of IPs and activation of PKD but did not change the abundance of
      PI4,5P2 Acute depletion of Golgi PI4P had no effect on these processes. These
      data suggest that most of the PM PI4,5P2 pool is not involved in GPCR-stimulated
      phosphoinositide hydrolysis and that PI4P at the PM is responsible for the bulk
      of receptor-stimulated phosphoinositide hydrolysis and DAG production.

PMID- 30206134
TI  - Systemic angiotensin II does not increase cardiac sympathetic nerve activity in
      normal conscious sheep.
AB  - While it is well established that centrally injected angiotensin II (Ang II) has
      potent actions on sympathetic nervous activity (SNA), it is less clear whether
      peripheral Ang II can immediately stimulate SNA. In particular, the contribution
      of cardiac sympathetic nerve activity (CSNA) to the acute pressor response is
      unknown. We therefore examined the effect of incremental doses of intravenous Ang
      II (3, 6, 12, 24, and 48 ng/kg/min each for 30 min) on CSNA in eight conscious
      sheep. Ang II infusions progressively increased plasma Ang II up to 50 pmol/l
      above control levels in dose-dependent fashion (P<0.001). This was associated
      with the expected increases in mean arterial pressure (MAP) above control levels
      from <10 mmHg at lower doses up to 23 mmHg at the highest dose (P<0.001). Heart
      rate and cardiac output fell progressively with each incremental Ang II infusion
      achieving significance at higher doses (P<0.001). There was no significant change
      in plasma catecholamines. At no dose did Ang II increase any of the CSNA
      parameters measured. Rather, CSNA burst frequency (P<0.001), burst incidence,
      (P=0.002), and burst area (P=0.004) progressively decreased achieving
      significance during the three highest doses. In conclusion, Ang II infused at
      physiologically relevant doses increased MAP in association with a reciprocal
      decrease in CSNA presumably via baroreceptor-mediated pathways. The present study
      provides no evidence that even low-dose systemic Ang II stimulates sympathetic
      traffic directed to the heart, in normal conscious sheep.

PMID- 30206133
TI  - FGFR2 gene polymorphism rs2981582 is associated with non-functioning pituitary
      adenomas in Chinese Han population: a case-control study.
AB  - The association of the fibroblast growth factor receptor 2 gene (FGFR2)
      polymorphism rs2981582 with breast cancer has been extensively studied, whereas
      the role of this polymorphism in non-functioning pituitary adenoma (NFPA) has not
      been elucidated. We thus investigated a potential association of rs2981582 with
      NFPA. A total of 79 patients and 142 healthy control participants were enrolled
      in our study. DNA of the participants was extracted from peripheral blood samples
      and genotyped by using the MassARRAY method. We found that the AA genotype was
      associated with a higher risk of developing NFPA (OR = 1.743, 95%CI: 1.151-2.64,
      P=0.008). After adjusting for risk factors, significant difference was still
      observed between the two groups (OR = 1.862, 95%CI: 1.172-2.957, P=0.008).
      Moreover, under the assumptions of the recessive model (OR = 3.051, 95%CI: 1.403
      6.635, P=0.005) and the additive model (AG: OR = 0.329, 95%CI: 0.144-0.755,
      P=0.009; AA: OR = 0.326, 95%CI: 0.141-0.757, P=0.009), rs2981582 was associated
      with an increased risk of NFPA. Our results proved that FGFR2 rs2981582 AA
      genotype was associated with a higher risk of NFPA. The recessive model and
      additive model also showed increased the risk of NFPA.

PMID- 30206137
TI  - Should the clinic matter to nonphysician scientists?
AB  - Translational medicine has been nurtured by the creation of M.D.-Ph.D. programs,
      a system that now needs to reinvent itself. Now, clinically oriented training
      programs targeting nonphysician scientists have opened new avenues to improve
      transdisciplinary approaches in health sciences.

PMID- 30206136
TI  - The Hippo pathway effector TAZ induces TEAD-dependent liver inflammation and
      tumors.
AB  - The Hippo signaling pathway regulates organ size and plays critical roles in
      maintaining tissue growth, homeostasis, and regeneration. Dysregulated in a wide
      spectrum of cancers, in mammals, this pathway is regulated by two key effectors,
      YAP and TAZ, that may functionally overlap. We found that TAZ promoted liver
      inflammation and tumor development. The expression of TAZ, but not YAP, in human
      liver tumors positively correlated with the expression of proinflammatory
      cytokines. Hyperactivated TAZ induced substantial myeloid cell infiltration into
      the liver and the secretion of proinflammatory cytokines through a TEAD-dependent
      mechanism. Furthermore, tumors with hyperactivated YAP and TAZ had distinct
      transcriptional signatures, which included the increased expression of
      inflammatory cytokines in TAZ-driven tumors. Our study elucidated a previously
      uncharacterized link between TAZ activity and inflammatory responses that
      influence tumor development in the liver.

PMID- 30206139
TI  - The kinases HipA and HipA7 phosphorylate different substrate pools in Escherichia
      coli to promote multidrug tolerance.
AB  - The bacterial serine-threonine protein kinase HipA promotes multidrug tolerance
      by phosphorylating the glutamate-tRNA ligase (GltX), leading to a halt in
      translation, inhibition of growth, and induction of a physiologically dormant
      state (persistence). The HipA variant HipA7 substantially increases persistence
      despite being less efficient at inhibiting cell growth. We postulated that this
      phenotypic difference was caused by differences in the substrates targeted by
      both kinases. We overproduced HipA and HipA7 in Escherichia coli and identified
      their endogenous substrates by SILAC-based quantitative phosphoproteomics. We
      confirmed that GltX was the main substrate of both kinase variants and likely the
      primary determinant of persistence. When HipA and HipA7 were moderately
      overproduced from plasmids, HipA7 targeted only GltX, but HipA phosphorylated
      several additional substrates involved in translation, transcription, and
      replication, such as ribosomal protein L11 (RplK) and the negative modulator of
      replication initiation, SeqA. HipA7 showed reduced kinase activity compared to
      HipA and targeted a substrate pool similar to that of HipA only when produced
      from a high-copy number plasmid. The kinase variants also differed in
      autophosphorylation, which was substantially reduced for HipA7. When produced
      endogenously from the chromosome, HipA showed no activity because of inhibition
      by the antitoxin HipB, whereas HipA7 phosphorylated GltX and phage shock protein
      PspA. Initial testing did not reveal a connection between HipA-induced
      phosphorylation of RplK and persistence or growth inhibition, suggesting that
      other HipA-specific substrates were likely responsible for growth inhibition. Our
      results contribute to the understanding of HipA7 action and present a resource
      for elucidating HipA-related persistence.

PMID- 30206138
TI  - Developmental phosphoproteomics identifies the kinase CK2 as a driver of Hedgehog
      signaling and a therapeutic target in medulloblastoma.
AB  - A major limitation of targeted cancer therapy is the rapid emergence of drug
      resistance, which often arises through mutations at or downstream of the drug
      target or through intrinsic resistance of subpopulations of tumor cells.
      Medulloblastoma (MB), the most common pediatric brain tumor, is no exception, and
      MBs that are driven by sonic hedgehog (SHH) signaling are particularly aggressive
      and drug-resistant. To find new drug targets and therapeutics for MB that may be
      less susceptible to common resistance mechanisms, we used a developmental
      phosphoproteomics approach in murine granule neuron precursors (GNPs), the
      developmental cell of origin of MB. The protein kinase CK2 emerged as a driver of
      hundreds of phosphorylation events during the proliferative, MB-like stage of GNP
      growth, including the phosphorylation of three of the eight proteins commonly
      amplified in MB. CK2 was critical to the stabilization and activity of the
      transcription factor GLI2, a late downstream effector in SHH signaling. CK2
      inhibitors decreased the viability of primary SHH-type MB patient cells in
      culture and blocked the growth of murine MB tumors that were resistant to
      currently available Hh inhibitors, thereby extending the survival of tumor
      bearing mice. Because of structural interactions, one CK2 inhibitor (CX-4945)
      inhibited both wild-type and mutant CK2, indicating that this drug may avoid at
      least one common mode of acquired resistance. These findings suggest that CK2
      inhibitors may be effective for treating patients with MB and show how
      phosphoproteomics may be used to gain insight into developmental biology and
      pathology.

PMID- 30206140
TI  - Revisiting the role of cholesterol in regulating the pore-formation mechanism of
      Vibrio cholerae cytolysin, a membrane-damaging beta-barrel pore-forming toxin.
AB  - Vibrio cholerae cytolysin (VCC) is a beta-barrel pore-forming toxin with potent
      membrane-damaging cell-killing activity. Previous studies employing the model
      membranes of lipid vesicles (liposomes) have shown that pore formation by VCC
      requires the presence of cholesterol in the liposome membranes. However, the
      exact role of cholesterol in the mode of action of VCC still remains unclear.
      Most importantly, implication of cholesterol, if any, in regulating the pore
      formation mechanism of VCC in the biomembranes of eukaryotic cells remains
      unexplored. Here, we show that the presence of cholesterol promotes the
      interaction of VCC with the membrane lipid bilayer, when non-lipid-dependent
      interactions are absent. However, in the case of biomembranes of human
      erythrocytes, where accessory interactions are available, cholesterol appears to
      play a less critical role in the binding step. Nevertheless, in the absence of an
      optimal level of membrane cholesterol in the human erythrocytes, membrane-bound
      fraction of the toxin remains trapped in the form of abortive oligomeric
      assembly, devoid of functional pore-forming activity. Our study also shows that
      VCC exhibits a prominent propensity to associate with the cholesterol-rich
      membrane micro-domains of human erythrocytes. Interestingly, mutation of the
      cholesterol-binding ability of VCC does not block association with the
      cholesterol-rich membrane micro-domains on human erythrocytes. Based on these
      results, we propose that the specific cholesterol-binding ability of VCC does not
      appear to dictate its association with the cholesterol-rich micro-domains on
      human erythrocytes. Rather, targeting of VCC toward the membrane micro-domains of
      human erythrocytes possibly acts to facilitate the cholesterol-dependent pore
      formation mechanism of the toxin.

PMID- 30206143
TI  - Breaking good news: an essential skill for avoiding too much medicine?

PMID- 30206142
TI  - Hereditary Kidney Disease: All Family Members Are Affected.

PMID- 30206141
TI  - Assessment of Perfusion and Oxygenation of the Human Renal Cortex and Medulla by
      Quantitative MRI during Handgrip Exercise.
AB  - BACKGROUND: Renal flow abnormalities are believed to play a central role in the
      pathogenesis of nephropathy and in primary and secondary hypertension, but are
      difficult to measure in humans. Handgrip exercise is known to reduce renal
      arterial flow (RAF) by means of increased renal sympathetic nerve activity.
      METHODS: To monitor medullary and cortical oxygenation under handgrip exercise
      reduced perfusion, we used contrast- and radiation-free magnetic resonance
      imaging (MRI) to measure regional changes in renal perfusion and blood
      oxygenation in ten healthy normotensive individuals during handgrip exercise. We
      used phase-contrast MRI to measure RAF, arterial spin labeling to measure
      perfusion, and both changes in transverse relaxation time (T2*) and dynamic blood
      oxygenation level-dependent imaging to measure blood oxygenation. RESULTS:
      Handgrip exercise induced a significant decrease in RAF. In the renal medulla,
      this was accompanied by an increase of oxygenation (reflected by an increase in
      T2*) despite a significant drop in medullary perfusion; the renal cortex showed a
      significant decrease in both perfusion and oxygenation. We also found a
      significant correlation (R 2=0.8) between resting systolic BP and the decrease in
      RAF during handgrip exercise. CONCLUSIONS: Renal MRI measurements in response to
      handgrip exercise were consistent with a sympathetically mediated decrease in
      RAF. In the renal medulla, oxygenation increased despite a reduction in
      perfusion, which we interpreted as the result of decreased GFR and a subsequently
      reduced reabsorptive workload. Our results further indicate that the renal flow
      response's sensitivity to sympathetic activation is correlated with resting BP,
      even within a normotensive range.

PMID- 30206145
TI  - Glad to be gay in India.

PMID- 30206146
TI  - Science and Culture: Raw data videos offer a glimpse into laboratory research.

PMID- 30206148
TI  - Dendritic actin delivery service.
AB  - The mechanisms by which the actin cytoskeleton regulates dendritic branching are
      not fully understood. Nithianandam and Chien (2018. J. Cell Biol.
      https://doi.org/10.1083/jcb.201711136) discover actin blobs, new structures that
      mediate dynamic actin delivery within a growing dendrite arbor and that mark
      sites of future branch formation.

PMID- 30206144
TI  - SCA8 RAN polySer protein preferentially accumulates in white matter regions and
      is regulated by eIF3F.
AB  - Spinocerebellar ataxia type 8 (SCA8) is caused by a bidirectionally transcribed
      CTG.CAG expansion that results in the in vivo accumulation of CUG RNA foci, an
      ATG-initiated polyGln and a polyAla protein expressed by repeat-associated non
      ATG (RAN) translation. Although RAN proteins have been reported in a growing
      number of diseases, the mechanisms and role of RAN translation in disease are
      poorly understood. We report a novel toxic SCA8 polySer protein which accumulates
      in white matter (WM) regions as aggregates that increase with age and disease
      severity. WM regions with polySer aggregates show demyelination and axonal
      degeneration in SCA8 human and mouse brains. Additionally, knockdown of the
      eukaryotic translation initiation factor eIF3F in cells reduces steady-state
      levels of SCA8 polySer and other RAN proteins. Taken together, these data show
      polySer and WM abnormalities contribute to SCA8 and identify eIF3F as a novel
      modulator of RAN protein accumulation.

PMID- 30206149
TI  - Transgender Adolescent Suicide Behavior.
AB  - OBJECTIVES: Our primary objective was to examine prevalence rates of suicide
      behavior across 6 gender identity groups: female; male; transgender, male to
      female; transgender, female to male; transgender, not exclusively male or female;
      and questioning. Our secondary objective was to examine variability in the
      associations between key sociodemographic characteristics and suicide behavior
      across gender identity groups. METHODS: Data from the Profiles of Student Life:
      Attitudes and Behaviors survey (N = 120 617 adolescents; ages 11-19 years) were
      used to achieve our objectives. Data were collected over a 36-month period: June
      2012 to May 2015. A dichotomized self-reported lifetime suicide attempts (never
      versus ever) measure was used. Prevalence statistics were compared across gender
      identity groups, as were the associations between sociodemographic
      characteristics (ie, age, parents' highest level of education, urbanicity, sexual
      orientation, and race and/or ethnicity) and suicide behavior. RESULTS: Nearly 14%
      of adolescents reported a previous suicide attempt; disparities by gender
      identity in suicide attempts were found. Female to male adolescents reported the
      highest rate of attempted suicide (50.8%), followed by adolescents who identified
      as not exclusively male or female (41.8%), male to female adolescents (29.9%),
      questioning adolescents (27.9%), female adolescents (17.6%), and male adolescents
      (9.8%). Identifying as nonheterosexual exacerbated the risk for all adolescents
      except for those who did not exclusively identify as male or female (ie,
      nonbinary). For transgender adolescents, no other sociodemographic characteristic
      was associated with suicide attempts. CONCLUSIONS: Suicide prevention efforts can
      be enhanced by attending to variability within transgender populations,
      particularly the heightened risk for female to male and nonbinary transgender
      adolescents.

PMID- 30206150
TI  - Ionic gating drives correlated insulator-metal transition.

PMID- 30206151
TI  - Language switching decomposed through MEG and evidence from bimodal bilinguals.
AB  - A defining feature of human cognition is the ability to quickly and accurately
      alternate between complex behaviors. One striking example of such an ability is
      bilinguals' capacity to rapidly switch between languages. This switching process
      minimally comprises disengagement from the previous language and engagement in a
      new language. Previous studies have associated language switching with increased
      prefrontal activity. However, it is unknown how the subcomputations of language
      switching individually contribute to these activities, because few natural
      situations enable full separation of disengagement and engagement processes
      during switching. We recorded magnetoencephalography (MEG) from American Sign
      Language-English bilinguals who often sign and speak simultaneously, which allows
      to dissociate engagement and disengagement. MEG data showed that turning a
      language "off" (switching from simultaneous to single language production) led to
      increased activity in the anterior cingulate cortex (ACC) and dorsolateral
      prefrontal cortex (dlPFC), while turning a language "on" (switching from one
      language to two simultaneously) did not. The distinct representational nature of
      these on and off processes was also supported by multivariate decoding analyses.
      Additionally, Granger causality analyses revealed that (i) compared with "turning
      on" a language, "turning off" required stronger connectivity between left and
      right dlPFC, and (ii) dlPFC activity predicted ACC activity, consistent with
      models in which the dlPFC is a top-down modulator of the ACC. These results
      suggest that the burden of language switching lies in disengagement from the
      previous language as opposed to engaging a new language and that, in the absence
      of motor constraints, producing two languages simultaneously is not necessarily
      more cognitively costly than producing one.

PMID- 30206154
TI  - Don't Go Grocery Shopping When Hungry! Systemic Signaling in Zinc Homeostasis.

PMID- 30206155
TI  - Handling the Heat: Methylome Variation Underlying Heat Tolerance in Cotton.

PMID- 30206153
TI  - Topological localization in out-of-equilibrium dissipative systems.
AB  - In this paper, we report that notions of topological protection can be applied to
      stationary configurations that are driven far from equilibrium by active,
      dissipative processes. We consider two physically disparate systems: stochastic
      networks governed by microscopic single-particle dynamics, and collections of
      driven interacting particles described by coarse-grained hydrodynamic theory. We
      derive our results by mapping to well-known electronic models and exploiting the
      resulting correspondence between a bulk topological number and the spectrum of
      dissipative modes localized at the boundary. For the Markov networks, we report a
      general procedure to uncover the topological properties in terms of the
      transition rates. For the active fluid on a substrate, we introduce a topological
      interpretation of fluid dissipative modes at the edge. In both cases, the
      presence of dissipative couplings to the environment that break time-reversal
      symmetry are crucial to ensuring topological protection. These examples
      constitute proof of principle that notions of topological protection do indeed
      extend to dissipative processes operating out of equilibrium. Such topologically
      robust boundary modes have implications for both biological and synthetic
      systems.

PMID- 30206156
TI  - Pupillary light reaction in preclinical Alzheimer's disease subjects compared
      with normal ageing controls.
AB  - BACKGROUND/AIMS: We wished to determine whether the pupillary light reaction can
      differentiate preclinical Alzheimer's disease (AD) subjects from normal ageing
      controls. We performed a prospective study evaluating the pupillary light
      reaction in a cohort of well-characterised subjects with preclinical AD versus
      normal ageing controls. METHODS: We recruited 57 subjects from our institution's
      Memory and Aging Project, part of our Alzheimer's Disease Research Center. All
      subjects completed PET-PiB imaging, cerebrospinal fluid analysis and at least 1
      neuropsychiatric assessment after their baseline assessment. All participants
      were assigned a clinical dementia rating and underwent a complete neuro
      ophthalmic examination. Participants were divided into a dementia biomarker+
      (preclinical AD) and biomarker- (normal ageing) group based on preclinical risk
      for Alzheimer's dementia. Pupillometry measurements were performed by using the
      NeurOptics PLR-200 Pupillometer. RESULTS: A total of 57 subjects were recruited
      with 24 dementia biomarker+ and 33 dementia biomarker- individuals. A variety of
      pupil flash response (PLR) parameters were assessed. Comparisons between groups
      were analysed using generalised estimating equations. None of the pupillary
      parameters showed a significant difference between groups. CONCLUSIONS: We found
      no significant differences in PLR between preclinical AD subjects and normal
      ageing controls. This suggests that the disease effect on the PLR may be small
      and difficult to detect at the earliest stages of the disease. Future studies
      could include larger sample size and chromatic pupillometry.

PMID- 30206152
TI  - Deconvolution of pro- and antiviral genomic responses in Zika virus-infected and
      bystander macrophages.
AB  - Genome-wide investigations of host-pathogen interactions are often limited by
      analyses of mixed populations of infected and uninfected cells, which lower
      sensitivity and accuracy. To overcome these obstacles and identify key mechanisms
      by which Zika virus (ZIKV) manipulates host responses, we developed a system that
      enables simultaneous characterization of genome-wide transcriptional and
      epigenetic changes in ZIKV-infected and neighboring uninfected primary human
      macrophages. We demonstrate that transcriptional responses in ZIKV-infected
      macrophages differed radically from those in uninfected neighbors and that
      studying the cell population as a whole produces misleading results. Notably, the
      uninfected population of macrophages exhibits the most rapid and extensive
      changes in gene expression, related to type I IFN signaling. In contrast,
      infected macrophages exhibit a delayed and attenuated transcriptional response
      distinguished by preferential expression of IFNB1 at late time points.
      Biochemical and genomic studies of infected macrophages indicate that ZIKV
      infection causes both a targeted defect in the type I IFN response due to
      degradation of STAT2 and reduces RNA polymerase II protein levels and DNA
      occupancy, particularly at genes required for macrophage identity. Simultaneous
      evaluation of transcriptomic and epigenetic features of infected and uninfected
      macrophages thereby reveals the coincident evolution of dominant proviral or
      antiviral mechanisms, respectively, that determine the outcome of ZIKV exposure.

PMID- 30206157
TI  - Visual acuity outcomes in cytomegalovirus retinitis: early versus late diagnosis.
AB  - AIMS: To determine if early dilated fundus examination for cytomegalovirus (CMV)
      retinitis leads to better visual outcomes in areas with limited HIV care, where
      patients may have long-standing retinitis before they are diagnosed with HIV.
      METHODS: Twenty-four eyes of 17 patients with CMV retinitis who were seen at an
      urban HIV clinic in Chiang Mai, Thailand, were included in this retrospective
      cohort study. Participants were divided into two groups based on the amount of
      time from the first documented CD4 count below 100 cells/mm3 to the first eye
      examination for CMV retinitis. Average visual acuity in each group was calculated
      at the time CMV retinitis was first detected, and then at 3, 6 and 12 months
      after diagnosis. RESULTS: The group of patients who received an eye examination
      within approximately 4 months of the initial low CD4 count measurement had better
      baseline visual acuity (median 20/30,IQR 20/20 to 20/60) compared with patients
      who presented later (median 20/80, 20/60 to hand motion); p=0.03). Visual acuity
      did not change significantly during the 12-month study period in either the early
      group (p=0.69) or late group (p=0.17). CONCLUSION: In this study, patients who
      were examined sooner after a low CD4 count had better vision than patients who
      were examined later. Routine early screening of patients with CD4 counts under
      below 100 cells/mm3 may detect earlier disease and prevent vision loss.

PMID- 30206158
TI  - Clinical profile, risk factors and outcome of medical, surgical and adjunct
      interventions in patients with Pythium insidiosum keratitis.
AB  - PURPOSE: To report clinical profile and compare management options for Pythium
      keratitis. METHOD: Retrospective interventional study of 46 patients diagnosed as
      Pythium keratitis by PCR DNA sequencing from January 2014 to July 2017.
      Interventions were categorised into medical management (MM) (topical azithromycin
      and linezolid with oral azithromycin at presentation), surgery (S) (therapeutic
      penetrating keratoplasty, TPK), surgical adjunct (SA) (cryotherapy+/-alcohol with
      TPK) and medical adjunct (MA) (MM after TPK). RESULTS: Primary treatment included
      MM (1 eye), SA (3 eyes) and S (42 eyes). Recurrence occurred in 27/43 eyes (MM+S
      group). Second surgery (S) was required in 11 eyes (TPK-2), with additional
      procedures (SA) in 10 eyes and evisceration in five eyes. 8/43 eyes received MA
      after TPK-1. One eye required TPK-3. Recurrence occured in all eyes that received
      MA (100%) and in 28 of 54 TPKs (51.8%) (TPK 1+2+3) in 42 eyes. Recurrence was
      noted in 1/14 (7.1%) that underwent SA. CONCLUSION: The currently available and
      recommended treatment for Pythium keratitis is surgical by means of a TPK and in
      worse cases evisceration. In our study, MM/MA measures showed no benefit with
      recurrence or worsening of infection requiring resurgery. Almost 50% of TPKs had
      a recurrence requiring resurgery. However, adjunctive procedures during TPK
      appear to have additional benefit with low risk of recurrence and could be
      included as routine care.

PMID- 30206160
TI  - Combining Vascular Normalization with an Oncolytic Virus Enhances Immunotherapy
      in Advanced Stage Ovarian Cancer.
AB  - PURPOSE: Intravenous delivery of oncolytic viruses often leads to tumor vascular
      shutdown, resulting in decreased tumor perfusion and elevated tumor hypoxia. We
      hypothesized that using 3TSR to normalize tumor vasculature prior to
      administration of an oncolytic Newcastle disease virus (NDV) would enhance virus
      delivery and trafficking of immunological cell subsets to the tumor core,
      resulting in systemically enhanced immunotherapy and regression of advanced stage
      Epithelial Ovarian Cancer (EOC). EXPERIMENTAL DESIGN: Using an orthotopic,
      syngeneic mouse model of advanced stage EOC, mice were pre-treated with 3TSR
      (4mg/kg per day) alone or followed by combination with fusogenic NDV(F3aa)
      (1.0x10 8PFU). RESULTS: Treatment with 3TSR normalized tumor vasculature,
      enhanced blood perfusion of primary EOC tumors and induced disease regression.
      Animals treated with combination therapy had the greatest reduction in primary
      tumor mass, ascites accumulation and secondary lesions (50% of mice were
      completely devoid of peritoneal metastases). Combining 3TSR+NDV(F3aa) led to
      enhanced trafficking of immunological cells into the primary tumor core.
      CONCLUSIONS: We have shown, for the first time that NDV, like other oncolytic
      viruses, is a potent mediator of acute vascular shutdown and that preventing this
      through vascular normalization can promote regression in a preclinical model of
      advanced stage ovarian cancer. This challenges the current focus on induction of
      intravascular thrombosis as a requisite for successful oncolytic virotherapy.

PMID- 30206159
TI  - Disparities in Neurotoxicity Risk and Outcomes among Pediatric Acute
      Lymphoblastic Leukemia Patients.
AB  - Purpose: Methotrexate chemotherapy can be associated with neurologic
      complications during therapy and long-term neurologic deficits. This study
      evaluated demographic and clinical factors associated with incidence of
      methotrexate neurotoxicity and described the impact of neurotoxicity on acute
      lymphoblastic leukemia (ALL) therapy in pediatric patients.Experimental Design:
      Patients were enrolled between 2012 and 2017 from three pediatric cancer
      treatment centers in the United States. Medical records for suspected cases of
      methotrexate neurotoxicity, defined as an acute neurologic event following
      methotrexate therapy, were reviewed. Cox proportional hazards models were used to
      estimate the association between race/ethnicity and methotrexate neurotoxicity.
      Multivariable linear regression models compared treatment outcomes between
      patients with and without methotrexate neurotoxicity.Results: Of the 280 newly
      diagnosed patients enrolled, 39 patients (13.9%) experienced methotrexate
      neurotoxicity. Compared with non-Hispanic whites, Hispanic patients experienced
      the greatest risk of methotrexate neurotoxicity (adjusted HR, 2.43; 95% CI, 1.06
      5.58) after accounting for sex, age at diagnosis, BMI Z-score at diagnosis, and
      ALL risk stratification. Patients who experienced a neurotoxic event received an
      average of 2.25 fewer doses of intrathecal methotrexate. Six of the 39 cases of
      neurotoxicity (15.4%) experienced relapse during the study period, compared with
      13 of the 241 (2.1%) patients without neurotoxicity (P = 0.0038).Conclusions:
      Hispanic ethnicity was associated with increased risk of methotrexate
      neurotoxicity, which was associated with treatment modifications and relapse.
      Understanding the mechanism and predictors of methotrexate neurotoxicity is
      important to improving treatment outcomes in pediatric ALL. Clin Cancer Res;
      24(20); 5012-7. (c)2018 AACR.

PMID- 30206161
TI  - Dual PAK4-NAMPT Inhibition Impacts Growth and Survival, and Increases Sensitivity
      to DNA-Damaging Agents in Waldenstrom Macroglobulinemia.
AB  - Purpose: p21-activated kinase 4 (PAK4) plays a significant biological and
      functional role in a number of malignancies, including multiple myeloma (MM). On
      the basis of our promising findings in MM, we here characterize PAK4 expression
      and role in WM cells, as well effect of dual PAK4-NAMPT inhibitor (KPT-9274)
      against WM cell growth and viability.Experimental Design: We have analyzed mRNA
      and protein expression levels of PAK4 in WM cells, and used loss-of-function
      approach to investigate its contribution to WM cell viability. We have further
      tested the in vitro and in vivo effect of KPT-9274 against WM cell growth and
      viability.Results: We report here high-level expression and functional role of
      PAK4 in WM, as demonstrated by shRNA-mediated knockdown; and significant impact
      of KPT-9274 on WM cell growth and viability. The growth inhibitory effect of KPT
      9274 was associated with decreased PAK4 expression and NAMPT activity, as well as
      induction of apoptosis. Interestingly, in WM cell lines treated with KPT-9274, we
      detected a significant impact on DNA damage and repair genes. Moreover, we
      observed that apart from inducing DNA damage, KPT-9274 specifically decreased
      RAD51 and the double-strand break repair by the homologous recombination pathway.
      As a result, when combined with a DNA alkylating agents bendamustine and
      melphalan, KPT-9274 provided a synergistic inhibition of cell viability in WM
      cell lines and primary patient WM cells in vitro and in vivo Conclusions: These
      results support the clinical investigation of KPT-9274 in combination with DNA
      damaging agent for treatment of WM. Clin Cancer Res; 1-9. (c)2018 AACR.

PMID- 30206162
TI  - Precision Medicine Approaches When Prostate Cancer Akts Up.
AB  - Ipatasertib combined with abiraterone in PTEN-null prostate cancer improved
      progression-free survival in a randomized phase II study of patients with
      metastatic castration-resistant prostate cancer (mCRPC), providing clinical
      evidence of reciprocal activation between the Akt and androgen receptor (AR)
      pathways. These data revive the rationale for targeting PTEN loss in prostate
      cancer. Clin Cancer Res; 1-3. (c)2018 AACR. See related article by de Bono et al.

PMID- 30206164
TI  - Trastuzumab Emtansine (T-DM1) in Patients with Previously Treated HER2
      Overexpressing Metastatic Non-Small Cell Lung Cancer: Efficacy, Safety, and
      Biomarkers.
AB  - Purpose: HER2-targeted therapy is not standard of care for HER2-positive non
      small cell lung cancer (NSCLC). This phase II study investigated efficacy and
      safety of the HER2-targeted antibody-drug conjugate trastuzumab emtansine (T-DM1)
      in patients with previously treated advanced HER2-overexpressing NSCLC.Patients
      and Methods: Eligible patients had HER2-overexpressing NSCLC (centrally tested
      IHC) and received previous platinum-based chemotherapy and targeted therapy in
      the case of EGFR mutation or ALK gene rearrangement. Patients were divided into
      cohorts based on HER2 IHC (2+, 3+). All patients received T-DM1 3.6 mg/kg
      intravenously every 3 weeks until disease progression or unacceptable toxicity.
      The primary endpoint was investigator-determined overall response rate (ORR)
      using RECIST v1.1.Results: Forty-nine patients received T-DM1 (29 IHC 2+, 20 IHC
      3+). No treatment responses were observed in the IHC 2+ cohort. Four partial
      responses were observed in the IHC 3+ cohort (ORR, 20%; 95% confidence interval,
      5.7%-43.7%). Clinical benefit rates were 7% and 30% in the IHC 2+ and 3+ cohorts,
      respectively. Response duration for the responders was 2.9, 7.3, 8.3, and 10.8
      months. Median progression-free survival and overall survival were similar
      between cohorts. Three of 4 responders had HER2 gene amplification. No new safety
      signals were observed.Conclusions: T-DM1 showed a signal of activity in patients
      with HER2-overexpressing (IHC 3+) advanced NSCLC. Additional investigation into
      HER2 pathway alterations is needed to refine the target population for T-DM1 in
      NSCLC; however, HER2 IHC as a single parameter was an insufficient predictive
      biomarker. Clin Cancer Res; 1-9. (c)2018 AACR.

PMID- 30206163
TI  - The Novel Bromodomain and Extraterminal Domain Inhibitor INCB054329 Induces
      Vulnerabilities in Myeloma Cells That Inform Rational Combination Strategies.
AB  - Introduction: Bromodomain and extraterminal domain (BET) proteins regulate the
      expression of many cancer-associated genes and pathways; BET inhibitors have
      demonstrated activity in diverse models of hematologic and solid tumors. We
      report the preclinical characterization of INCB054329, a structurally distinct
      BET inhibitor that has been investigated in phase I clinical trials.Methods: We
      used multiple myeloma models to investigate vulnerabilities created by INCB054329
      treatment that could inform rational combinations.Results: In addition to c-MYC,
      INCB054329 decreased expression of oncogenes FGFR3 and NSD2/MMSET/WHSC1, which
      are deregulated in t(4;14)-rearranged cell lines. The profound suppression of
      FGFR3 sensitized the t(4;14)-positive cell line OPM-2 to combined treatment with
      a fibroblast growth factor receptor inhibitor in vivo In addition, we show that
      BET inhibition across multiple myeloma cell lines resulted in suppressed
      interleukin (IL)-6 Janus kinase-signal transducers and activators of
      transcription (JAK-STAT) signaling. INCB054329 displaced binding of BRD4 to the
      promoter of IL6 receptor (IL6R) leading to reduced levels of IL6R and diminished
      signaling through STAT3. Combination with JAK inhibitors (ruxolitinib or
      itacitinib) further reduced JAK-STAT signaling and synergized to inhibit myeloma
      cell growth in vitro and in vivo This combination potentiated tumor growth
      inhibition in vivo, even in the MM1.S model of myeloma that is not intrinsically
      sensitive to JAK inhibition alone.Conclusions: Preclinical data reveal insights
      into vulnerabilities created in myeloma cells by BET protein inhibition and
      potential strategies that can be leveraged in clinical studies to enhance the
      activity of INCB054329. Clin Cancer Res; 1-12. (c)2018 AACR.

PMID- 30206165
TI  - Antibody-Fc/FcR Interaction on Macrophages as a Mechanism for Hyperprogressive
      Disease in Non-small Cell Lung Cancer Subsequent to PD-1/PD-L1 Blockade.
AB  - Background: Hyperprogression (HP), a paradoxical boost in tumor growth, was
      described in a subset of patients treated with immune checkpoint inhibitors
      (ICI). Neither clinicopathologic features nor biological mechanisms associated
      with HP have been identified.Experimental Design: Among 187 patients with non
      small cell lung cancer (NSCLC) treated with ICI at our institute, cases with HP
      were identified according to clinical and radiologic criteria. Baseline
      histologic samples from patients treated with ICI were evaluated by IHC for
      myeloid and lymphoid markers. T-cell-deficient mice, injected with human lung
      cancer cells and patient-derived xenografts (PDX) belonging to specific
      mutational subsets, were assessed for tumor growth after treatment with
      antibodies against mouse and human programmed death receptor-1 (PD-1). The immune
      microenvironment was evaluated by flow cytometry and IHC.Results: Among 187
      patients, 152 were evaluable for clinical response. We identified four
      categories: 32 cases were defined as responders (21%), 42 patients with stable
      disease (27.7%), 39 cases were defined as progressors (25.7%), and 39 patients
      with HP (25.7%). Pretreatment tissue samples from all patients with HP showed
      tumor infiltration by M2-like CD163+CD33+PD-L1+ clustered epithelioid
      macrophages. Enrichment by tumor-associated macrophages (TAM) was observed, even
      in tumor nodules from immunodeficient mice injected with human lung cancer cells
      and with PDXs. In these models, tumor growth was enhanced by treatment with anti
      PD-1 but not anti-PD-1 F(ab)2 fragments.Conclusions: These results suggest a
      crucial role of TAM reprogramming, upon Fc receptor engagement by ICI, eventually
      inducing HP and provide clues on a distinctive immunophenotype potentially able
      to predict HP. Clin Cancer Res; 1-11. (c)2018 AACR.

PMID- 30206166
TI  - Induction of HIF-1alpha by HIV-1 Infection in CD4+ T Cells Promotes Viral
      Replication and Drives Extracellular Vesicle-Mediated Inflammation.
AB  - Chronic immune activation and inflammation are hallmarks of HIV-1 infection and a
      major cause of serious non-AIDS events in HIV-1-infected individuals on
      antiretroviral treatment (ART). Herein, we show that cytosolic double-stranded
      DNA (dsDNA) generated in infected CD4+ T cells during the HIV-1 replication cycle
      promotes the mitochondrial reactive oxygen species (ROS)-dependent stabilization
      of the transcription factor hypoxia-inducible factor 1alpha (HIF-1alpha), which
      in turn, enhances viral replication. Furthermore, we show that induction of HIF
      1alpha promotes the release of extracellular vesicles (EVs). These EVs foster
      inflammation by inducing the secretion of gamma interferon by bystander CD4+ T
      cells and secretion of interleukin 6 (IL-6) and IL-1beta by bystander macrophages
      through an HIF-1alpha-dependent pathway. Remarkably, EVs obtained from plasma
      samples from HIV-1-infected individuals also induced HIF-1alpha activity and
      inflammation. Overall, this study demonstrates that HIF-1alpha plays a crucial
      role in HIV-1 pathogenesis by promoting viral replication and the release of EVs
      that orchestrate lymphocyte- and macrophage-mediated inflammatory
      responses.IMPORTANCE Human immunodeficiency virus type 1 (HIV-1) is a very
      important global pathogen that preferentially targets CD4+ T cells and causes
      acquired immunodeficiency syndrome (AIDS) if left untreated. Although
      antiretroviral treatment efficiently suppresses viremia, markers of immune
      activation and inflammation remain higher in HIV-1-infected patients than in
      uninfected individuals. The hypoxia-inducible factor 1alpha (HIF-1alpha) is a
      transcription factor that plays a fundamental role in coordinating cellular
      metabolism and function. Here we show that HIV-1 infection induces HIF-1alpha
      activity and that this transcription factor upholds HIV-1 replication. Moreover,
      we demonstrate that HIF-1alpha plays a key role in HIV-1-associated inflammation
      by promoting the release of extracellular vesicles which, in turn, trigger the
      secretion of inflammatory mediators by noninfected bystander lymphocytes and
      macrophages. In summary, we identify that the coordinated actions of HIF-1alpha
      and extracellular vesicles promote viral replication and inflammation, thus
      contributing to HIV-1 pathogenesis.

PMID- 30206167
TI  - The Pseudomonas aeruginosa Complement of Lactate Dehydrogenases Enables Use of d-
      and l-Lactate and Metabolic Cross-Feeding.
AB  - Pseudomonas aeruginosa is the most common cause of chronic, biofilm-based lung
      infections in patients with cystic fibrosis (CF). Sputum from patients with CF
      has been shown to contain oxic and hypoxic subzones as well as millimolar
      concentrations of lactate. Here, we describe the physiological roles and
      expression patterns of P. aeruginosa lactate dehydrogenases in the contexts of
      different growth regimes. P. aeruginosa produces four enzymes annotated as
      lactate dehydrogenases, three of which are known to contribute to anaerobic or
      aerobic metabolism in liquid cultures. These three are LdhA, which reduces
      pyruvate to d-lactate during anaerobic survival, and LldE and LldD, which oxidize
      d-lactate and l-lactate, respectively, during aerobic growth. We demonstrate that
      the fourth enzyme, LldA, performs redundant l-lactate oxidation during growth in
      aerobic cultures in both a defined MOPS (morpholinepropanesulfonic acid)-based
      medium and synthetic CF sputum media. However, LldA differs from LldD in that its
      expression is induced specifically by the l-enantiomer of lactate. We also show
      that the P. aeruginosa lactate dehydrogenases perform functions in colony
      biofilms that are similar to their functions in liquid cultures. Finally, we
      provide evidence that the enzymes LdhA and LldE have the potential to support
      metabolic cross-feeding in biofilms, where LdhA can catalyze the production of d
      lactate in the anaerobic zone, which is then used as a substrate in the aerobic
      zone. Together, these observations further our understanding of the metabolic
      pathways that can contribute to P. aeruginosa growth and survival during CF lung
      infection.IMPORTANCE Lactate is thought to serve as a carbon and energy source
      during chronic infections. Sites of bacterial colonization can contain two
      enantiomers of lactate: the l-form, generally produced by the host, and the d
      form, which is usually produced by bacteria, including the pulmonary pathogen
      Pseudomonas aeruginosa Here, we characterize P. aeruginosa's set of four enzymes
      that it can use to interconvert pyruvate and lactate, the functions of which
      depend on the availability of oxygen and specific enantiomers of lactate. We also
      show that anaerobic pyruvate fermentation triggers production of the aerobic d
      lactate dehydrogenase in both liquid cultures and biofilms, thereby enabling
      metabolic cross-feeding of lactate over time and space between subpopulations of
      cells. These metabolic pathways might contribute to P. aeruginosa growth and
      survival in the lung.

PMID- 30206168
TI  - Candida albicans Hyphal Expansion Causes Phagosomal Membrane Damage and Luminal
      Alkalinization.
AB  - Macrophages rely on phagosomal acidity to destroy engulfed microorganisms. To
      survive this hostile response, opportunistic fungi such as Candida albicans
      developed strategies to evade the acidic environment. C. albicans is polymorphic
      and able to convert from yeast to hyphae, and this transition is required to
      subvert the microbicidal activity of the phagosome. However, the phagosomal
      lumen, which is acidic and nutrient deprived, is believed to inhibit the yeast-to
      hypha transition. To account for this apparent paradox, it was recently proposed
      that C. albicans produces ammonia that alkalinizes the phagosome, thus
      facilitating yeast-to-hypha transition. We reexamined the mechanism underlying
      phagosomal alkalinization by applying dual-wavelength ratiometric pH
      measurements. The phagosomal membrane was found to be highly permeable to
      ammonia, which is therefore unlikely to account for the pH elevation. Instead, we
      find that yeast-to-hypha transition begins within acidic phagosomes and that
      alkalinization is a consequence of proton leakage induced by excessive membrane
      distension caused by the expanding hypha.IMPORTANCEC. albicans is the most common
      cause of nosocomial fungal infection, and over 3 million people acquire life
      threatening invasive fungal infections every year. Even if antifungal drugs
      exist, almost half of these patients will die. Despite this, fungi remain
      underestimated as pathogens. Our study uses quantitative biophysical approaches
      to demonstrate that yeast-to-hypha transition occurs within the nutrient
      deprived, acidic phagosome and that alkalinization is a consequence, as opposed
      to the cause, of hyphal growth.

PMID- 30206169
TI  - Mechanical Genomic Studies Reveal the Role of d-Alanine Metabolism in Pseudomonas
      aeruginosa Cell Stiffness.
AB  - The stiffness of bacteria prevents cells from bursting due to the large osmotic
      pressure across the cell wall. Many successful antibiotic chemotherapies target
      elements that alter mechanical properties of bacteria, and yet a global view of
      the biochemistry underlying the regulation of bacterial cell stiffness is still
      emerging. This connection is particularly interesting in opportunistic human
      pathogens such as Pseudomonas aeruginosa that have a large (80%) proportion of
      genes of unknown function and low susceptibility to different families of
      antibiotics, including beta-lactams, aminoglycosides, and quinolones. We used a
      high-throughput technique to study a library of 5,790 loss-of-function mutants
      covering ~80% of the nonessential genes and correlated P. aeruginosa individual
      genes with cell stiffness. We identified 42 genes coding for proteins with
      diverse functions that, when deleted individually, decreased cell stiffness by
      >20%. This approach enabled us to construct a "mechanical genome" for P.
      aeruginosa d-Alanine dehydrogenase (DadA) is an enzyme that converts d-Ala to
      pyruvate that was included among the hits; when DadA was deleted, cell stiffness
      decreased by 18% (using multiple assays to measure mechanics). An increase in the
      concentration of d-Ala in cells downregulated the expression of genes in
      peptidoglycan (PG) biosynthesis, including the peptidoglycan-cross-linking
      transpeptidase genes ponA and dacC Consistent with this observation,
      ultraperformance liquid chromatography-mass spectrometry analysis of murein from
      P. aeruginosa cells revealed that dadA deletion mutants contained PG with reduced
      cross-linking and altered composition compared to wild-type cells.IMPORTANCE The
      mechanical properties of bacteria are important for protecting cells against
      physical stress. The cell wall is the best-characterized cellular element
      contributing to bacterial cell mechanics; however, the biochemistry underlying
      its regulation and assembly is still not completely understood. Using a unique
      high-throughput biophysical assay, we identified genes coding proteins that
      modulate cell stiffness in the opportunistic human pathogen Pseudomonas
      aeruginosa This approach enabled us to discover proteins with roles in a diverse
      range of biochemical pathways that influence the stiffness of P. aeruginosa
      cells. We demonstrate that d-Ala-a component of the peptidoglycan-is tightly
      regulated in cells and that its accumulation reduces expression of machinery that
      cross-links this material and decreases cell stiffness. This research
      demonstrates that there is much to learn about mechanical regulation in bacteria,
      and these studies revealed new nonessential P. aeruginosa targets that may
      enhance antibacterial chemotherapies or lead to new approaches.

PMID- 30206170
TI  - Structural Analysis of the Interaction between the Bacterial Cell Division
      Proteins FtsQ and FtsB.
AB  - Most bacteria and archaea use the tubulin homologue FtsZ as its central organizer
      of cell division. In Gram-negative Escherichia coli bacteria, FtsZ recruits
      cytosolic, transmembrane, periplasmic, and outer membrane proteins, assembling
      the divisome that facilitates bacterial cell division. One such divisome
      component, FtsQ, a bitopic membrane protein with a globular domain in the
      periplasm, has been shown to interact with many other divisome proteins. Despite
      its otherwise unknown function, it has been shown to be a major divisome
      interaction hub. Here, we investigated the interactions of FtsQ with FtsB and
      FtsL, two small bitopic membrane proteins that act immediately downstream of
      FtsQ. We show in biochemical assays that the periplasmic domains of E. coli FtsB
      and FtsL interact with FtsQ, but not with each other. Our crystal structure of
      FtsB bound to the beta domain of FtsQ shows that only residues 64 to 87 of FtsB
      interact with FtsQ. A synthetic peptide comprising those 24 FtsB residues
      recapitulates the FtsQ-FtsB interactions. Protein deletions and structure-guided
      mutant analyses validate the structure. Furthermore, the same structure-guided
      mutants show cell division defects in vivo that are consistent with our structure
      of the FtsQ-FtsB complex that shows their interactions as they occur during cell
      division. Our work provides intricate details of the interactions within the
      divisome and also provides a tantalizing view of a highly conserved protein
      interaction in the periplasm of bacteria that is an excellent target for cell
      division inhibitor searches.IMPORTANCE In most bacteria and archaea, filaments of
      FtsZ protein organize cell division. FtsZ forms a ring structure at the division
      site and starts the recruitment of 10 to 20 downstream proteins that together
      form a multiprotein complex termed the divisome. The divisome is thought to
      facilitate many of the steps required to make two cells out of one. FtsQ and FtsB
      are part of the divisome, with FtsQ being a central hub, interacting with most of
      the other divisome components. Here we show for the first time in detail how FtsQ
      interacts with its downstream partner FtsB and show that mutations that disturb
      the interface between the two proteins effectively inhibit cell division.

PMID- 30206171
TI  - Ecophylogenetics Clarifies the Evolutionary Association between Mammals and Their
      Gut Microbiota.
AB  - Our knowledge of how the gut microbiome relates to mammalian evolution benefits
      from the identification of gut microbial taxa that are unexpectedly prevalent or
      unexpectedly conserved across mammals. Such taxa enable experimental
      determination of the traits needed for such microbes to succeed as gut
      generalists, as well as those traits that impact mammalian fitness. However, the
      punctuated resolution of microbial taxonomy may limit our ability to detect
      conserved gut microbes, especially in cases in which broadly related microbial
      lineages possess shared traits that drive their apparent ubiquity across mammals.
      To advance the discovery of conserved mammalian gut microbes, we developed a
      novel ecophylogenetic approach to taxonomy that groups microbes into taxonomic
      units based on their shared ancestry and their common distribution across
      mammals. Applying this approach to previously generated gut microbiome data
      uncovered monophyletic clades of gut bacteria that are conserved across mammals.
      It also resolved microbial clades exclusive to and conserved among particular
      mammalian lineages. Conserved clades often manifest phylogenetic patterns, such
      as cophylogeny with their host, that indicate that they are subject to selective
      processes, such as host filtering. Moreover, this analysis identified variation
      in the rate at which mammals acquire or lose conserved microbial clades and
      resolved a human-accelerated loss of conserved clades. Collectively, the data
      from this study reveal mammalian gut microbiota that possess traits linked to
      mammalian phylogeny, point to the existence of a core set of microbes that
      comprise the mammalian gut microbiome, and clarify potential evolutionary or
      ecologic mechanisms driving the gut microbiome's diversification throughout
      mammalian evolution.IMPORTANCE Our understanding of mammalian evolution has
      become microbiome-aware. While emerging research links mammalian biodiversity and
      the gut microbiome, we lack insight into which microbes potentially impact
      mammalian evolution. Microbes common to diverse mammalian species may be strong
      candidates, as their absence in the gut may affect how the microbiome
      functionally contributes to mammalian physiology to adversely affect fitness.
      Identifying such conserved gut microbes is thus important to ultimately assessing
      the microbiome's potential role in mammalian evolution. To advance their
      discovery, we developed an approach that identifies ancestrally related groups of
      microbes that distribute across mammals in a way that indicates their collective
      conservation. These conserved clades are presumed to have evolved a trait in
      their ancestor that matters to their distribution across mammals and which has
      been retained among clade members. We found not only that such clades do exist
      among mammals but also that they appear to be subject to natural selection and
      characterize human evolution.

PMID- 30206172
TI  - Transcriptional Regulation Buffers Gene Dosage Effects on a Highly Expressed
      Operon in Salmonella.
AB  - Highly expressed genes are commonly located close to the origin of replication of
      bacterial chromosomes (OriC). This location skew is thought to reflect selective
      advantages associated with gene dosage effects during the replication cycle. The
      expression of constitutively expressed genes can vary up to fivefold based on
      chromosomal location, but it is not clear what level of variation would occur in
      naturally regulated operons. We tested the magnitude of the chromosome location
      effect using EF-Tu (tufA, tufB), an abundant protein whose cellular level
      correlates with, and limits, the maximum growth rate. We translocated the
      Salmonella tufB operon to four locations across the chromosome. The distance from
      OriC had only a small effect on growth rate, consistent with this operon having
      the natural ability to upregulate expression and compensate for reduced gene
      dosage. In contrast, when the total EF-Tu concentration was limiting for the
      growth rate (tufA deleted), we observed a strong gene dosage effect when tufB was
      located further from OriC. However, only a short period of experimental evolution
      was required before the bacteria adapted to this EF-Tu starvation situation by
      acquiring genetic changes that increased expression levels from the translocated
      tufB gene, restoring growth rates. Our findings demonstrate that, at least for
      the tufB operon, gene dosage is probably not the dominant force selecting for a
      chromosomal location close to OriC. We suggest that the colocation of highly
      expressed genes close to OriC might instead be selected because it enhances their
      coregulation during various growth states, with gene dosage being a secondary
      benefit.IMPORTANCE A feature of bacterial chromosomes is that highly expressed
      essential genes are usually located close to the origin of replication. Because
      bacteria have overlapping cycles of replication, genes located close to the
      origin will often be present in multiple copies, and this is thought to be of
      selective benefit where high levels of expression support high growth rate.
      However, the magnitude of this selective effect and whether other forces could be
      at play are poorly understood. To study this, we translocated a highly expressed
      essential operon, tufB, to different locations and measured growth fitness. We
      found that transcriptional regulation buffered the effects of translocation and
      that even under conditions where growth rate was reduced, genetic changes that
      increased the expression of tufB were easily and rapidly selected. We conclude,
      at least for tufB, that forces other than gene dosage may be significant in
      selecting for chromosomal location.

PMID- 30206175
TI  - Mosaic Drug Efflux Gene Sequences from Commensal Neisseria Can Lead to Low-Level
      Azithromycin Resistance Expressed by Neisseria gonorrhoeae Clinical Isolates.
AB  - In a previous mBio article, Wadsworth and colleagues (mBio 9:e01419-18, 2018,
      https://doi.org/10.1128/mBio.01419-18) described Neisseria gonorrhoeae isolates
      that express low levels of azithromycin (Azi) resistance. Whole-genome sequencing
      and bioinformatic analysis suggested that the isolates had acquired DNA from
      commensal Neisseria spp. that caused numerous nucleotide changes in the mtr
      locus, which contains genes for a transcriptional repressor (MtrR) and three
      proteins (MtrC-MtrD-MtrE) that form a multidrug efflux pump known to export
      macrolides. Strong regions of linkage disequilibrium mapped to the overlapping
      mtrR and mtrCDE promoters and mtrD. Genetic analyses revealed that these mosaic
      like sequences increased transcription of mtrCDE and MtrD function, respectively.
      These changes also had strong epistatic effects that collectively were
      responsible for decreased susceptibility to MtrCDE substrates, including Azi. The
      report emphasizes the importance of gene exchange among neisserial species and
      development of antibiotic resistance in gonococci, both of which have
      ramifications for detection of resistance markers and efficacy of antibiotic
      treatment regimens for gonorrhea.

PMID- 30206176
TI  - Leading US cancer researcher failed to disclose industry ties in dozens of
      articles.

PMID- 30206173
TI  - Tumor Necrosis Factor Alpha Induces Reactivation of Human Cytomegalovirus
      Independently of Myeloid Cell Differentiation following Posttranscriptional
      Establishment of Latency.
AB  - We used the Kasumi-3 model to study human cytomegalovirus (HCMV) latency and
      reactivation in myeloid progenitor cells. Kasumi-3 cells were infected with HCMV
      strain TB40/Ewt-GFP, flow sorted for green fluorescent protein-positive (GFP+)
      cells, and cultured for various times to monitor establishment of latency, as
      judged by repression of viral gene expression (RNA/DNA ratio) and loss of virus
      production. We found that, in the vast majority of cells, latency was established
      posttranscriptionally in the GFP+ infected cells: transcription was initially
      turned on and then turned off. We also found that some of the GFP- cells were
      infected, suggesting that latency might be established in these cells at the
      outset of infection. We were not able to test this hypothesis because some GFP-
      cells expressed lytic genes and thus it was not possible to separate them from
      GFP- quiescent cells. In addition, we found that the pattern of expression of
      lytic genes that have been associated with latency, including UL138, US28, and
      RNA2.7, was the same as that of other lytic genes, indicating that there was no
      preferential expression of these genes once latency was established. We confirmed
      previous studies showing that tumor necrosis factor alpha (TNF-alpha) induced
      reactivation of infectious virus, and by analyzing expression of the progenitor
      cell marker CD34 as well as myeloid cell differentiation markers in IE+ cells
      after treatment with TNF-alpha, we showed that TNF-alpha induced transcriptional
      reactivation of IE gene expression independently of differentiation. TNF-alpha
      mediated reactivation in Kasumi-3 cells was correlated with activation of NF
      kappaB, KAP-1, and ATM.IMPORTANCE HCMV is an important human pathogen that
      establishes lifelong latent infection in myeloid progenitor cells and reactivates
      frequently to cause significant disease in immunocompromised people. Our
      observation that viral gene expression is first turned on and then turned off to
      establish latency suggests that there is a host defense, which may be myeloid
      cell specific, responsible for transcriptional silencing of viral gene
      expression. Our observation that TNF-alpha induces reactivation independently of
      differentiation provides insight into molecular mechanisms that control
      reactivation.

PMID- 30206174
TI  - Structural Basis of Pan-Ebolavirus Neutralization by a Human Antibody against a
      Conserved, yet Cryptic Epitope.
AB  - Only one naturally occurring human antibody has been described thus far that is
      capable of potently neutralizing all five ebolaviruses. Here we present two
      crystal structures of this rare, pan-ebolavirus neutralizing human antibody in
      complex with Ebola virus and Bundibugyo virus glycoproteins (GPs), respectively.
      The structures delineate the key protein and glycan contacts for binding that are
      conserved across the ebolaviruses, explain the antibody's unique broad
      specificity and neutralization activity, and reveal the likely mechanism behind a
      known escape mutation in the fusion loop region of GP2. We found that the epitope
      of this antibody, ADI-15878, extends along the hydrophobic paddle of the fusion
      loop and then dips down into a highly conserved pocket beneath the N-terminal
      tail of GP2, a mode of recognition unlike any other antibody elicited against
      Ebola virus, and likely critical for its broad activity. The fold of Bundibugyo
      virus glycoprotein, not previously visualized, is similar to the fold of Ebola
      virus GP, and ADI-15878 binds to each virus's GP with a similar strategy and
      angle of attack. These findings will be useful in deployment of this antibody as
      a broad-spectrum therapeutic and in the design of immunogens that elicit the
      desired broadly neutralizing immune response against all members of the
      ebolavirus genus and filovirus family.IMPORTANCE There are five different members
      of the Ebolavirus genus. Provision of vaccines and treatments able to protect
      against any of the five ebolaviruses is an important goal of public health.
      Antibodies are a desired result of vaccines and can be delivered directly as
      therapeutics. Most antibodies, however, are effective against only one or two,
      not all, of these pathogens. Only one human antibody has been thus far described
      to neutralize all five ebolaviruses, antibody ADI-15878. Here we describe the
      molecular structure of ADI-15878 bound to the relevant target proteins of Ebola
      virus and Bundibugyo virus. We explain how it achieves its rare breadth of
      activity and propose strategies to design improved vaccines capable of eliciting
      more antibodies like ADI-15878.

PMID- 30206178
TI  - Research integrity and the law that never was.
AB  - Evidence-based medicine is arguably among the most important innovations of the
      modern era, but publication bias and inadequate research transparency are serious
      issues affecting the very foundation of evidence-based practice. Despite this
      truth, these crucial issues have gone largely unaddressed or inadequately
      addressed for a distressingly long period of time. Regulatory efforts have thus
      far proven insufficient in eliminating these issues. Fortunately, the last 5
      years in particular have seen developments that one hopes will contribute to the
      eradication of these issues and a future where we can look back on these issues
      as a sordid story of our past. However, much like the purported fixes of the
      past, time will be the final arbiter of the efficacy of remedial measures
      currently underway. This article chronicles the history of these issues, failed
      attempts to fix these issues, and what can be and is being done with the hope of
      bringing about true resolution.

PMID- 30206179
TI  - UK women living shorter lives than most European counterparts.

PMID- 30206177
TI  - Diverse Functions of Macrophages in Different Tumor Microenvironments.
AB  - Tumor-associated macrophages are a major constituent of malignant tumors and are
      known to stimulate key steps in tumor progression. In our review in this journal
      in 2006, we postulated that functionally distinct subsets of these cells exist in
      different areas within solid tumors. Here, we review the many experimental and
      clinical studies conducted since then to investigate the function(s), regulation,
      and clinical significance of macrophages in these sites. The latter include three
      sites of cancer cell invasion, tumor nests, the tumor stroma, and areas close to,
      or distant from, the tumor vasculature. A more complete understanding of
      macrophage diversity in tumors could lead to the development of more selective
      therapies to restore the formidable, anticancer functions of these cells. Cancer
      Res; 78(19); 5492-503. (c)2018 AACR.

PMID- 30206180
TI  - Knockout of the Hmt1p Arginine Methyltransferase in Saccharomyces cerevisiae
      Leads to the Dysregulation of Phosphate-associated Genes and Processes.
AB  - Hmt1p is the predominant arginine methyltransferase in Saccharomyces cerevisiae
      Its substrate proteins are involved in transcription, transcriptional regulation,
      nucleocytoplasmic transport and RNA splicing. Hmt1p-catalyzed methylation can
      also modulate protein-protein interactions. Hmt1p is conserved from unicellular
      eukaryotes through to mammals where its ortholog, PRMT1, is lethal upon knockout.
      In yeast, however, the effect of knockout on the transcriptome and proteome has
      not been described. Transcriptome analysis revealed downregulation of phosphate
      responsive genes in hmt1Delta, including acid phosphatases PHO5, PHO11, and
      PHO12, phosphate transporters PHO84 and PHO89 and the vacuolar transporter
      chaperone VTC3 Analysis of the hmt1Delta proteome revealed decreased abundance of
      phosphate-associated proteins including phosphate transporter Pho84p, vacuolar
      alkaline phosphatase Pho8p, acid phosphatase Pho3p and subunits of the vacuolar
      transporter chaperone complex Vtc1p, Vtc3p and Vtc4p. Consistent with this,
      phosphate homeostasis was dysregulated in hmt1Delta cells, showing decreased
      extracellular phosphatase levels and decreased total Pi in phosphate-depleted
      medium. In vitro, we showed that transcription factor Pho4p can be methylated at
      Arg-241, which could explain phosphate dysregulation in hmt1Delta if interplay
      exists with phosphorylation at Ser-242 or Ser-243, or if Arg-241 methylation
      affects the capacity of Pho4p to homodimerize or interact with Pho2p. However,
      the Arg-241 methylation site was not validated in vivo and the localization of a
      Pho4p-GFP fusion in hmt1Delta was not different from wild type. To our knowledge,
      this is the first study to reveal an association between Hmt1p and phosphate
      homeostasis and one which suggests a regulatory link between S-adenosyl
      methionine and intracellular phosphate.

PMID- 30206181
TI  - Postprandial bile acid levels in intestine and plasma reveal altered biliary
      circulation in chronic pancreatitis patients.
AB  - Bile acid (BA) secretion and circulation in chronic pancreatitis (CP) patients
      with exocrine pancreatic insufficiency (EPI) were investigated by simultaneously
      measuring postprandial levels of individual BAs in duodenal contents and blood
      plasma using LC-MS/MS. CP patients and healthy volunteers (HVs) were intubated
      with gastric and duodenal tubes prior to the administration of a test meal and
      continuous aspiration of duodenal contents. Pancreatic lipase outputs in CP
      patients were very low (0.7 +/- 0.2 mg) versus HVs (116.7 +/- 68.1 mg; P <
      0.005), thus confirming the severity of EPI. Duodenal BA outputs were reduced in
      CP patients (1.00 +/- 0.89 mmol; 0.47 +/- 0.42 g) versus HVs (5.52 +/- 4.53 mmol;
      2.62 +/- 2.14 g; P < 0.15). Primary to secondary BA ratio was considerably higher
      in CP patients (38.09 +/- 48.1) than HVs (4.15 +/- 2.37; P < 0.15), indicating an
      impaired transformation of BAs by gut microbiota. BA concentrations were found
      below the critical micellar concentration in CP patients, while a high BA
      concentration peak corresponding to gallbladder emptying was evidenced in HVs.
      Conversely, BA plasma concentration was increased in CP patients versus HVs
      suggesting a cholangiohepatic shunt of BA secretion. Alterations of BA
      circulation and levels may result from the main biliary duct stenosis observed in
      these CP patients and may aggravate the consequences of EPI on lipid
      malabsorption.

PMID- 30206182
TI  - Relative quantification of deuterated omega-3 and -6 fatty acids and their lipid
      turnover in PC12 cell membranes using TOF-SIMS.
AB  - Understanding FA metabolism and lipid synthesis requires a lot of information
      about which FAs and lipids are formed within the cells. We focused on the use of
      deuterated substrates of 100 MUM alpha-linolenic acid and linoleic acid to
      determine the relative amounts of their converted PUFAs and specific
      phospholipids that are incorporated into cell plasma membranes. Time-of-flight
      secondary ion mass spectrometry (TOF-SIMS) was used to image and analyze lipids
      in model cell membranes with and without FA treatment. Because of its high
      spatial resolution, TOF-SIMS can be used to simultaneously provide both chemical
      information and distribution of various molecules in the sample surface down to
      the subcellular scale. Data obtained from this analysis of isotopes in the cell
      samples were used to calculate the relative amounts of long-chain PUFAs and
      phospholipids from their precursors, alpha-linolenic acid and linoleic acid. Our
      results show that the FA treatments induced an increase in the amounts of alpha
      linolenic acid and linoleic acid and their long-chain conversion products.
      Moreover, an enhanced level of phospholipid turnover of these FAs in lipids such
      as phosphatidylcholines, phosphatidylethanolamines, and phosphatidylinositols was
      also observed in the cell plasma membrane.

PMID- 30206183
TI  - Vascular endothelial function is impaired by aerosol from a single IQOS HeatStick
      to the same extent as by cigarette smoke.
AB  - BACKGROUND: Heated tobacco products (also called 'heat-not-burn' products) heat
      tobacco at temperatures below that of combustion, causing nicotine and other
      compounds to aerosolise. One such product, IQOS from Philip Morris International,
      is being marketed internationally with claims of harm reduction. We sought to
      determine whether exposure to IQOS aerosol impairs arterial flow-mediated
      dilation (FMD), a measure of vascular endothelial function that is impaired by
      tobacco smoke. METHODS: We exposed anaesthetised rats (n=8/group) via nose cone
      to IQOS aerosol from single HeatSticks, mainstream smoke from single Marlboro Red
      cigarettes or clean air for a series of consecutive 30 s cycles over 1.5-5 min.
      Each cycle consisted of 15 or 5 s of exposure followed by removal from the nose
      cone. We measured pre-exposure and postexposure FMD, and postexposure serum
      nicotine and cotinine. RESULTS: FMD was impaired comparably by ten 15 s exposures
      and ten 5 s exposures to IQOS aerosol and to cigarette smoke, but not by clean
      air. Serum nicotine levels were similar to plasma levels after humans have smoked
      one cigarette, confirming that exposure conditions had real-world relevance.
      Postexposure nicotine levels were ~4.5-fold higher in rats exposed to IQOS than
      to cigarettes, despite nicotine being measured in the IQOS aerosol at ~63% the
      amount measured in smoke. When IQOS exposure was briefer, leading to comparable
      serum nicotine levels to the cigarette group, FMD was still comparably impaired.
      CONCLUSIONS: Acute exposures to IQOS aerosol impairs FMD in rats. IQOS use does
      not necessarily avoid the adverse cardiovascular effects of smoking cigarettes.

PMID- 30206184
TI  - SOX9/FXYD3/Src Axis Is Critical for ER+ Breast Cancer Stem Cell Function.
AB  - The presence of cancer stem cells (CSC), which possess the ability of self
      renewal and cancer initiation, is correlated with poor prognosis and drug
      resistance of breast cancer patients. But the molecular regulatory networks for
      maintenance of CSC function still remain unclear. Here, we identified that an
      estrogen-inducible gene FXYD3, whose expression is significantly upregulated in
      ER+ breast CSCs, is a critical player for regulating ER+ breast CSC function.
      FXYD3 amplification is crucial in mediating tamoxifen resistance in ER+ breast
      cancer cells. Interestingly, we also find that stem cell-related transcription
      factor SOX9 directly promotes FXYD3 expression, and FXYD3 is indispensable for
      SOX9 nucleus localization, thus forming a positive regulatory feedback loop for
      FXYD3 amplification and function. In terms of mechanism, FXYD3 interacts with Src
      and ERalpha to form an activated complex and triggers Src to transduce nongenomic
      estrogen signaling for facilitating ER+ breast CSCs. Collectively, these results
      establish a critical role for SOX9/FXYD3/Src axis in boosting nongenomic estrogen
      signaling and SOX9 nucleus entry, which is required for maintenance of ER+ breast
      CSCs and endocrine resistance. Targeting FXYD3-mediated pathway might be a
      promising therapeutic strategy for hormone therapy-refractory ER+ breast
      cancer.Implications: SOX9/FXYD3/Src axis is critical for promoting CSC function
      and tamoxifen resistance in ER+ breast cancer. Mol Cancer Res; 1-12. (c)2018
      AACR.

PMID- 30206185
TI  - Y-box proteins combine versatile cold shock domains and arginine-rich motifs
      (ARMs) for pleiotropic functions in RNA biology.
AB  - Y-box proteins are single-strand DNA- and RNA-binding proteins distinguished by a
      conserved cold shock domain (CSD) and a variable C-terminal domain organized into
      alternating short modules rich in basic or acidic amino acids. A huge literature
      depicts Y-box proteins as highly abundant, staggeringly versatile proteins that
      interact with all mRNAs and function in most forms of mRNA-specific regulation.
      The mechanisms by which Y-box proteins recognize mRNAs are unclear, because their
      CSDs bind a jumble of diverse elements, and the basic modules in the C-terminal
      domain are considered to bind nonspecifically to phosphates in the RNA backbone.
      A survey of vertebrate Y-box proteins clarifies the confusing names for Y-box
      proteins, their domains, and RNA-binding motifs, and identifies several novel
      conserved sequences: first, the CSD is flanked by linkers that extend its binding
      surface or regulate co-operative binding of the CSD and N-terminal and C-terminal
      domains to proteins and RNA. Second, the basic modules in the C-terminal domain
      are bona fide arginine-rich motifs (ARMs), because arginine is the predominant
      amino acid and comprises 99% of basic residues. Third, conserved differences in
      AA (amino acid) sequences between isoforms probably affect RNA-binding
      specificity. C-terminal ARMs connect with many studies, demonstrating that ARMs
      avidly bind sites containing specific RNA structures. ARMs crystallize insights
      into the under-appreciated contributions of the C-terminal domain to site
      specific binding by Y-box proteins and difficulties in identifying site-specific
      binding by the C-terminal domain. Validated structural biology techniques are
      available to elucidate the mechanisms by which YBXprot (Y-box element-binding
      protein) CSDs and ARMs identify targets.

PMID- 30206187
TI  - Estimating the Timing of Multiple Admixture Pulses During Local Ancestry
      Inference.
AB  - Admixture, the mixing of genetically distinct populations, is increasingly
      recognized as a fundamental biological process. One major goal of admixture
      analyses is to estimate the timing of admixture events. Whereas most methods
      today can only detect the most recent admixture event, here, we present
      coalescent theory and associated software that can be used to estimate the timing
      of multiple admixture events in an admixed population. We extensively validate
      this approach and evaluate the conditions under which it can successfully
      distinguish one- from two-pulse admixture models. We apply our approach to real
      and simulated data of Drosophila melanogaster We find evidence of a single very
      recent pulse of cosmopolitan ancestry contributing to African populations, as
      well as evidence for more ancient admixture among genetically differentiated
      populations in sub-Saharan Africa. These results suggest our method can quantify
      complex admixture histories involving genetic material introduced by multiple
      discrete admixture pulses. The new method facilitates the exploration of
      admixture and its contribution to adaptation, ecological divergence, and
      speciation.

PMID- 30206189
TI  - USP7 and USP47 deubiquitinases regulate NLRP3 inflammasome activation.
AB  - The assembly and activation of the inflammasomes are tightly regulated by post
      translational modifications, including ubiquitin. Deubiquitinases (DUBs)
      counteract the addition of ubiquitin and are essential regulators of immune
      signalling pathways, including those acting on the inflammasome. How DUBs control
      the assembly and activation of inflammasomes is unclear. Here, we show that the
      DUBs USP7 and USP47 regulate inflammasome activation in macrophages. Chemical
      inhibition of USP7 and USP47 blocks inflammasome formation, independently of
      transcription, by preventing ASC oligomerisation and speck formation. We also
      provide evidence that the ubiquitination status of NLRP3 itself is altered by
      inhibition of USP7 and USP47. Interestingly, we found that the activity of USP7
      and USP47 increased in response to inflammasome activators. Using CRISPR/Cas9 in
      the macrophage cell line THP-1, we show that inflammasome activation is reduced
      when both USP7 and USP47 are knocked down. Altogether, these data reveal a new
      post-transcriptional role for USP47 and USP7 in inflammation by regulating
      inflammasome activation and the release of the pro-inflammatory cytokines IL
      1beta and IL-18, and implicate dual USP7 and USP47 inhibitors as potential
      therapeutic agents for inflammatory disease.

PMID- 30206188
TI  - Opposing kinesin complexes queue at plus tips to ensure microtubule catastrophe
      at cell ends.
AB  - In fission yeast, the lengths of interphase microtubule (iMT) arrays are adapted
      to cell length to maintain cell polarity and to help centre the nucleus and cell
      division ring. Here, we show that length regulation of iMTs is dictated by
      spatially regulated competition between MT-stabilising Tea2/Tip1/Mal3 (Kinesin-7)
      and MT-destabilising Klp5/Klp6/Mcp1 (Kinesin-8) complexes at iMT plus ends.
      During MT growth, the Tea2/Tip1/Mal3 complex remains bound to the plus ends of
      iMT bundles, thereby restricting access to the plus ends by Klp5/Klp6/Mcp1, which
      accumulate behind it. At cell ends, Klp5/Klp6/Mcp1 invades the space occupied by
      the Tea2/Tip1/Tea1 kinesin complex triggering its displacement from iMT plus ends
      and MT catastrophe. These data show that in vivo, whilst an iMT length-dependent
      model for catastrophe factor accumulation has validity, length control of iMTs is
      an emergent property reflecting spatially regulated competition between distinct
      kinesin complexes at the MT plus tip.

PMID- 30206191
TI  - [Effectiveness of Telemonitoring Intervention in Children and Adolescents with
      Asthma: A Systematic Review and Meta-Analysis].
AB  - PURPOSE: This review aimed to evaluate the effectiveness of telemonitoring (TM)
      in the management of children and adolescents with asthma. METHODS: We searched
      Ovid-MEDLINE, Ovid-EMBASE, CENTRAL (Cochrane Central Register of Controlled
      Trials), CINAHL (Cumulative Index to Nursing and Allied Health Literature), and 5
      domestic databases to identify randomized controlled trials (RCTs) published
      through December 2017. Two reviewers independently selected relevant studies,
      assessed methodological quality and extracted data. We performed a meta-analysis
      of TM versus usual care and summarized the intervention characteristics of
      included studies. RESULTS: Of the 3,095 articles identified, 8 RCTs (9 articles)
      were included in this review. The type of TM intervention of included studies was
      varying across studies (transmitted data, transmission frequency, data review,
      etc.). The pooled asthma control score was not significantly different between TM
      and usual care (standardized mean difference 0.04, 95% confidence interval (CI) 
      0.20~0.28). Another pooled analysis demonstrated no statistically significant
      difference in asthma exacerbation between TM and usual care (odds ratio 0.95, 95%
      CI 0.43~2.09). Overall, the pooled results from these studies revealed that TM
      did not lead to clinically significant improvements in health outcomes, but some
      studies in our analysis suggested that TM increased patient medication adherence
      and intervention adherence. CONCLUSION: The current evidence base does not
      demonstrate any differences between TM intervention and usual care, but TM
      intervention might be considered a promising strategy for the delivery of self
      management support for children and adolescents with asthma. Further well
      designed studies are needed to assess the effects on clinical outcomes.

PMID- 30206186
TI  - Multiple Mechanisms Inactivate the LIN-41 RNA-Binding Protein To Ensure a Robust
      Oocyte-to-Embryo Transition in Caenorhabditis elegans.
AB  - In the nematode Caenorhabditis elegans, the conserved LIN-41 RNA-binding protein
      is a translational repressor that coordinately controls oocyte growth and meiotic
      maturation. LIN-41 exerts these effects, at least in part, by preventing the
      premature activation of the cyclin-dependent kinase CDK-1 Here we investigate the
      mechanism by which LIN-41 is rapidly eliminated upon the onset of meiotic
      maturation. Elimination of LIN-41 requires the activities of CDK-1 and multiple
      SCF (Skp1, Cul1, and F-box protein)-type E3 ubiquitin ligase subunits, including
      the conserved substrate adaptor protein SEL-10/Fbw7/Cdc4, suggesting that LIN-41
      is a target of ubiquitin-mediated protein degradation. Within the LIN-41 protein,
      two nonoverlapping regions, Deg-A and Deg-B, are individually necessary for LIN
      41 degradation; both contain several potential phosphodegron sequences, and at
      least one of these sequences is required for LIN-41 degradation. Finally, Deg-A
      and Deg-B are sufficient, in combination, to mediate SEL-10-dependent degradation
      when transplanted into a different oocyte protein. Although LIN-41 is a potent
      inhibitor of protein translation and M phase entry, the failure to eliminate LIN
      41 from early embryos does not result in the continued translational repression
      of LIN-41 oocyte messenger RNA targets. Based on these observations, we propose a
      model for the elimination of LIN-41 by the SEL-10 E3 ubiquitin ligase and suggest
      that LIN-41 is inactivated before it is degraded. Furthermore, we provide
      evidence that another RNA-binding protein, the GLD-1 tumor suppressor, is
      regulated similarly. Redundant mechanisms to extinguish translational repression
      by RNA-binding proteins may both control and provide robustness to irreversible
      developmental transitions, including meiotic maturation and the oocyte-to-embryo
      transition.

PMID- 30206192
TI  - [Development and Effects of Social Learning Theory Based Eye-Health Program for
      Preschoolers].
AB  - PURPOSE: The purpose of this study was to develop an eye-health program based on
      social learning theory (EPST) of preschoolers and evaluate its effectiveness.
      METHODS: A nonequivalent control group pre-post test design was utilized and 141
      six-year-old preschoolers and their parents participated (experimental group=69,
      control group=72) in the study. The EPST in this study included eye-health
      education and eye exercises. Attention, memory, replay, motivation,
      reinforcement, and self-efficacy were used as interventional strategies. To
      examine the effectiveness of EPST, proficiency in eye-health activities,
      refractive power, and visual acuity were measured before and after the
      intervention. Data were analyzed with SPSS WIN 21.0 using the Shapiro-Wilk test,
      chi2-test, Mann-Whitney U test and Wilcoxon signed rank test. RESULTS: Following
      the intervention, eye-health activities, refractive power, and visual acuity
      significantly improved in the experimental group compared to the control group.
      CONCLUSION: The results of this study suggest that EPST is effective in improving
      eye-health activities, refractive power, and visual acuity in preschoolers, and
      its wider implementation in educational institutions will promise improved eye
      health among preschoolers.

PMID- 30206193
TI  - [Development and Psychometric Testing of the Clinical Nursing Competency Scale
      for Clinical Preceptor Use (CNCS-CP)].
AB  - PURPOSE: The purpose of this study was to develop and establish the psychometric
      properties of a clinical nursing competency evaluation tool to be utilized by
      clinical preceptors. METHODS: The initial items were identified through in-depth
      literature review and field interviews based on a hybrid model. Content
      validation of the items was evaluated through three rounds of content validity
      testing. Participants were 34 clinical preceptors and 443 nursing students
      participating in clinical practice. Data were analyzed using exploratory and
      confirmatory factor analysis, convergence and discriminant validity, internal
      consistency and inter-rater reliability. RESULTS: The final scale consisted of 23
      items and four factors, fundamental nursing skills performance, critical thinking
      skills based on the nursing process, basic nursing knowledge, and professional
      attitude; these factor explained 69.7% of the total variance. The analysis with
      multi-trait/multi-item matrix correlation coefficients yielded 100.0% and 95.7 %
      convergence and discriminant validity, respectively. Cronbach's alpha for the
      total items was .95. The four subscale model tested by confirmatory factor
      analysis was satisfactory. Inter-rater reliability ranged from .912 to .967.
      CONCLUSION: This scale was found to be a reliable and valid instrument that
      clinical preceptors can apply for evaluating the clinical nursing competency of
      nursing students in clinical settings.

PMID- 30206190
TI  - Single-cell transcriptomics reveals distinct inflammation-induced microglia
      signatures.
AB  - Microglia are specialized parenchymal-resident phagocytes of the central nervous
      system (CNS) that actively support, defend and modulate the neural environment.
      Dysfunctional microglial responses are thought to worsen CNS diseases;
      nevertheless, their impact during neuroinflammatory processes remains largely
      obscure. Here, using a combination of single-cell RNA sequencing and multicolour
      flow cytometry, we comprehensively profile microglia in the brain of
      lipopolysaccharide (LPS)-injected mice. By excluding the contribution of other
      immune CNS-resident and peripheral cells, we show that microglia isolated from
      LPS-injected mice display a global downregulation of their homeostatic signature
      together with an upregulation of inflammatory genes. Notably, we identify
      distinct microglial activated profiles under inflammatory conditions, which
      greatly differ from neurodegenerative disease-associated profiles. These results
      provide insights into microglial heterogeneity and establish a resource for the
      identification of specific phenotypes in CNS disorders, such as neuroinflammatory
      and neurodegenerative diseases.

PMID- 30206194
TI  - [Effects of Group Rational Emotive Behavior Therapy on the Nurses' Job Stress,
      Burnout, Job Satisfaction, Organizational Commitment and Turnover Intention].
AB  - PURPOSE: This study aimed to develop a Group REBT program with group counseling
      for nurses and test the effect of group counseling on their job stress, burnout,
      job satisfaction, organizational commitment, and turnover intention. METHODS: A
      quasi-experimental study with nonequivalent control group design was employed to
      identify the effect of the Group REBT program on nurses' job stress, burnout, job
      satisfaction, organizational commitment, and turnover intention. Data were
      collected from 47 participants from two hospitals. The data from the experimental
      (n=23) and control (n=24) groups were analyzed from January 5 to April 3, 2015.
      The Group REBT program was conducted eight tmes in all, once a week, with each
      session lasting 180 minutes. The effect of experimental intervention was measured
      for each group using a series of structured questionnaires at each of the phases:
      Pre-intervention, post-intervention (immediately after intervention), and post
      intervention (four weeks after intervention). Following this, the significance of
      the changes in the scores was tested. RESULTS: The scores of the experimental
      group, which received the Group REBT program, were compared with those of the
      control group; the hypotheses were supported in terms of job stress (F=8.85,
      p<.001), burnout (F=5.62, p=.022), job satisfaction (F=2.70, p=.042),
      organizational commitment (F=2.97, p=.048), and turnover intention (F=4.60,
      p=.012). CONCLUSION: The Group REBT program was shown to be an effective
      intervention that could reduce nurses' job stress and burnout and increase job
      satisfaction and organizational commitment. Therefore, the Group REBT program can
      be adopted by nursing organizations to strategically decrease nurses' turnover
      intention.

PMID- 30206195
TI  - [The Effects of an Acceptance-Commitment Therapy Based Stress Management Program
      on Hospitalization Stress, Self-Efficacy and Psychological Well-Being of
      Inpatients with Schizophrenia].
AB  - PURPOSE: The purpose of this study was to construct an acceptance-commitment
      therapy (ACT)-based stress management program for inpatients with schizophrenia
      and to examine its effects on hospitalization stress, self-efficacy, and
      psychological well-being. METHODS: A non-equivalent control group pretest
      posttest design was used. Participants were 44 inpatients with a diagnosis of
      schizophrenia. The experimental group (n=22) received the ACT-based stress
      management program twice a week for a total of four weeks. The control group
      (n=22) received the usual care from their primary health care providers. The
      study was carried out from August 7 to September 1, 2017, and data were analyzed
      using IBM SPSS/WIN 22.0 with a Chi-square test, Fisher's exact test, and an
      independent t-test. RESULTS: The experimental group showed a significant decrease
      in hospitalization stress (t=5.09, p<.001) and an increase in self-efficacy
      (t=2.44, p=.019). However, there was no significant difference in psychological
      well-being between the two groups (t=0.13, p=.894). CONCLUSION: The results of
      this study suggest that the ACT-based stress management program can be used as an
      effective mental health nursing intervention for hospitalization stress and self
      efficacy for inpatients with schizophrenia.

PMID- 30206196
TI  - [Factors Influencing Psychosocial Well-Being in Family Caregivers of People with
      Amyotrophic Lateral Sclerosis].
AB  - PURPOSE: The purpose of this study was to identify factors influencing
      psychosocial well-being in family caregivers of patients with amyotrophic lateral
      sclerosis (ALS). METHODS: A descriptive correlational design was used. The
      transactional model of stress and coping was used to investigate the psychosocial
      well-being of 137 family caregivers of patients with ALS. Data were collected
      through self-reported questionnaires from January to November 2016. Data were
      analyzed using an independent t-test, one-way ANOVA, Pearson's correlation, and
      hierarchical multiple regression analysis with the SPSS WIN 21.0 program.
      RESULTS: The regression model had an adjusted R2 of .49, which indicated that
      meaning-focused coping, social support, ALS patient-family caregiver relationship
      (especially a spousal relationship), and tracheostomy were significant predictors
      of caregivers' psychosocial well-being. CONCLUSION: Meaning-focused coping and
      social support significantly influenced caregivers' psychosocial well-being.
      Therefore, interventions to improve caregivers' psychosocial well-being must
      focus on increasing meaning-focused coping and social support resources.

PMID- 30206197
TI  - [The Effects of Hand Massage in Patients Who Underwent Transradial Percutaneous
      Coronary Intervention].
AB  - PURPOSE: This study aimed to determine the effect of hand massage in patients who
      underwent transradial percutaneous coronary intervention. METHODS: This was a
      quasi-experimental study with a nonequivalent control group and non-synchronized
      design. The study included 30 patients in the experimental group and 30 in the
      control group. Hand massage was performed 2 times for 5 minutes each in the
      experimental group and the control group only received usual nursing
      interventions. Pain, level of discomfort, and vital signs were defined as key
      outcome measures, and the data were analyzed using the chi-square test, an
      independent t-test, Mann-Whitney U test, repeated-measures analysis of variance,
      and Friedman test. RESULTS: Significant differences were observed between the 2
      groups in the pain score (F=7.91, p=.003), discomfort score (F=18.15, p<.001),
      pulse (F=12.92, p<.001), and respiration rate (chi2=19.35, p<.001). CONCLUSION:
      Hand massage can be a helpful nursing intervention for transradial percutaneous
      coronary intervention by reducing pain and discomfort to a considerable degree.

PMID- 30206198
TI  - Differences in Factors Associated with Depressive Symptoms between Urban and
      Rural Female Adolescents in Korea.
AB  - PURPOSE: To examine the prevalence of depressive symptoms and differentiate
      factors associated with them in urban and rural areas by applying the Ecological
      Models of Health Behavior. METHODS: We employed a cross-sectional design and
      convenience sample of 460 female adolescents. The instruments included the
      Adolescent Mental-Health Problem-Behavior Questionnaire (AMPQ-II) and the Beck
      Depression Inventory (BDI). RESULTS: Depressive symptoms were confirmed in 15.7%
      of urban adolescents and 22.9% of rural adolescents (p<.05). In the urban group,
      perception of health and stress associated with school performance were
      significantly associated with depressive symptoms. In the rural group,
      academic/internet related problems and rule violations were significantly
      associated with depressive symptoms (p<.05). General life happiness,
      worry/anxiety, and mood/suicidal ideation were common factors in both urban and
      rural areas (p<.05). CONCLUSION: Multiple factors were associated with depressive
      symptoms, and those significant factors differed between urban and rural female
      youths. Accordingly, tailored approaches are required considering urban and rural
      differences. The approaches should include intrapersonal, interpersonal, and
      organizational levels of interventions.

PMID- 30206199
TI  - [Impact of Uncertainty on the Anxiety of Hospitalized Pregnant Women Diagnosed
      with Preterm Labor: Focusing on Mediating Effect of Uncertainty Appraisal and
      Coping Style].
AB  - PURPOSE: This study aimed to test the mediating effect of uncertainty appraisal
      and coping style in the relation between uncertainty and anxiety in hospitalized
      pregnant women diagnosed with preterm labor. METHODS: The participants were 105
      pregnant women diagnosed with preterm labor in hospitals in Korea. Data were
      collected from July to October 2017. The measurements included the Uncertainty in
      Illness Scale, Uncertainty Appraisal Scale, Coping Style Scale, and State Anxiety
      Inventory. Data were analyzed using descriptive statistics, an independent t
      test, correlation, and multiple regression following the Baron and Kenny method
      and Sobel test for mediation. RESULTS: The mean score for anxiety was 2.29 out of
      4.00 points and for uncertainty it was 2.46 out of 5.00 points. There were
      significant correlations among uncertainty, uncertainty danger appraisal,
      uncertainty opportunity appraisal, problem-focused coping, emotion-focused
      coping, and anxiety. Uncertainty danger appraisal (beta=.64, p<.001) had a
      complete mediating effect in the relation between uncertainty and anxiety
      (Z=4.54, p<.001). Uncertainty opportunity appraisal (beta=-.45, p<.001) had a
      complete mediating effect in the relation between uncertainty and anxiety
      (Z=3.28, p<.001). Emotion-focused coping (beta=-.23, p=.021) had a partial
      mediating effect in the relation between uncertainty and anxiety (Z=2.02,
      p=.044). CONCLUSION: Nursing intervention programs focusing on managing
      uncertainty appraisal and improving emotion-focused coping are highly recommended
      to decrease anxiety in hospitalized pregnant women diagnosed with preterm labor.

PMID- 30206200
TI  - Subperiosteal Hematoma of the Iliac Bone: An Unusual Cause of Acute Hip Pain
      after a Fall.
AB  - BACKGROUND Subperiosteal hematoma (SPH) of the iliac bone is an extremely
      uncommon clinical entity that occurs mostly in young patients with a history of a
      recent fall or sports-related injury. Patients usually complain of severe hip
      pain after a fall, mimicking femoral neck fracture. CASE REPORT An 18-year-old
      female was transported to our hospital complaining of pain in her left hip after
      falling on her buttocks while engaging in martial arts. Ultrasound of her left
      iliac region revealed a subperiosteal mass on the internal aspect of the iliac
      bone lifting the iliac muscle. SPH of the iliac bone was suspected, which was
      also evident on pelvis and hip magnetic resonance imaging. Repetitive ultrasound
      did not reveal hematoma expansion. She was discharged from the hospital the next
      day without femoral neuropathy. CONCLUSIONS Physicians should be aware of our
      report, which highlights a patient with the rare clinical condition of SPH of the
      iliac bone occurring immediately after a fall. The differential diagnosis of
      acute hip pain, which mimics femoral neck fracture, should be considered in young
      patients. Ultrasound of the iliac region may be useful in detection and further
      management of SPH of the iliac bone.

PMID- 30206201
TI  - The Effect of Pulmonary Rehabilitation in Mountain Environment on Exercise
      Capacity and Quality of Life in Patients with Chronic Obstructive Pulmonary
      Disease (COPD) and Chronic Bronchitis.
AB  - BACKGROUND We aimed to test the effectiveness of the pulmonary rehabilitation in
      a mountain environment on the pulmonary function, physical performance, dyspnea,
      affective factors, and quality of life (QoL) in patients with chronic obstructive
      pulmonary disease (COPD) and chronic bronchitis (CB), as well as to determine
      predictors of clinical improvement. MATERIAL AND METHODS 128 consecutive patients
      (90 diagnosed with COPD and 38 diagnosed with CB) underwent comprehensive
      pulmonary rehabilitation for a duration of 3 weeks in one of 3 mountain health
      resorts in the High Tatras. The examination included spirometry (FEV1 and
      FEV1/FVC), 6-minute walk test (6MWT), Borg scale of dyspnea, and assessment of
      depression (Zung score), anxiety (Beck score), and QoL using the SF-36 scales.
      RESULTS After the study intervention, all patients in both monitored groups
      demonstrated significant improvements in objective measurements in which large
      treatment effect was achieved (for FEV1 eta2=0.218, for 6MWT eta2=0.771).
      Similarly, in subjective measurements a large effect was achieved (for the Beck
      score: eta2=0.599, for the Zung score: eta2=0.536). QoL improved after the
      intervention in all the monitored SF-36 scales in both groups (P<0.001 for all).
      In patients with COPD, the improvement of exercise capacity was positively
      correlated with baseline 6MWT and FEV1, and negatively with the Beck anxiety
      score and the Borg dyspnea score, whereas, only improvement in the mental summary
      component of QoL was negatively correlated with baseline 6MWT and FEV1 (P<0.05
      for all). CONCLUSIONS Rehabilitation in a mountain environment has proven to be
      effective in both the reported diagnoses of COPD and CB. Improvements in both
      functional and subjective indicators were observed. These findings support the
      use of this treatment modality.

PMID- 30206202
TI  - HDAC6 inhibitor TST strengthens the antiproliferative effects of PI3K/mTOR
      inhibitor BEZ235 in breast cancer cells via suppressing RTK activation.
AB  - NVP-BEZ235 (BEZ235), an available dual PI3K/mTOR inhibitor, showed antitumor
      effect and provided a therapy strategy in carcinomas. However, the acquired
      upregulation of multiple receptor tyrosine kinases (RTKs) by NVP-BEZ235 in tumors
      limits its clinical efficacy. HDAC6, a class II histone deacetylase, is
      associated with expressions of multiple RTKs. The aim of this study was to detect
      whether co-treatment with HDAC6 inhibitor Tubastatin A (TST) would enhance the
      anticancer effects of BEZ235 in breast cancer cells. In this study, we described
      that treatment of breast cancer cell lines (T47D, BT474, and MDA-MB-468) with
      BEZ235 significantly triggered PI3K/mTOR signaling inactivation and increased
      multiple RTK expression, including EGFR, HER2, HER3, IGF-1 receptor, insulin
      receptor, and their phosphorylation levels. The adding of TST destabilized these
      RTKs in those breast cancer cells. Co-treatment with BEZ235 and TST reduced cell
      proliferative rate by strengthening Akt inactivation. In addition, the
      combination of these two drugs also cooperatively arrested cell cycle and DNA
      synthesis. In conclusion, the co-treatment with PI3K/mTOR inhibitor BEZ235 and
      HDAC6 inhibitor TST displayed additive antiproliferative effects on breast cancer
      cells through inactivating RTKs and established a rationable combination therapy
      to treat breast cancer.

PMID- 30206203
TI  - Ectopic hTERT expression facilitates reprograming of fibroblasts derived from
      patients with Werner syndrome as a WS cellular model.
AB  - The induced pluripotent stem cell (iPSC) technology has provided a unique
      opportunity to develop disease-specific models and personalized treatment for
      genetic disorders, and is well suitable for the study of Werner syndrome (WS), an
      autosomal recessive disease with adult onset of premature aging caused by
      mutations in the RecQ like helicase (WRN) gene. WS-derived fibroblasts were
      previously shown to be able to generate iPSCs; however, it remains elusive how WS
      derived iPSCs behave and whether they are able to mimic the disease-specific
      phenotype. The present study was designed to address these issues. Unexpectedly,
      we found that a specific WS fibroblast line of homozygous truncation mutation was
      difficult to be reprogrammed by using the Yamanaka factors even under hypoxic
      conditions due to their defect in induction of hTERT, the catalytic unit of
      telomerase. Ectopic expression of hTERT restores the ability of this WS
      fibroblast line to form iPSCs, although with a low efficiency. To examine the
      phenotype of WRN-deficient pluripotent stem cells, we also generated WRN knockout
      human embryonic stem (ES) cells by using the CRISPR/Cas9 method. The iPSCs
      derived from WS-hTERT cells and WRN-/- ESCs are fully pluripotent, express
      pluripotent markers and can differentiate into three germ layer cells; however,
      WS-iPSCs and WRN-/- ESCs show S phase defect in cell cycle progression. Moreover,
      WS-iPSCs and WRN-/- ESCs, like WS patient-derived fibroblasts, remain
      hypersensitive to topoisomerase inhibitors. Collectively, WS-derived iPSCs and
      WRN-/- ESCs mimic the intrinsic disease phenotype, which may serve as a suitable
      disease model, whereas not be good for a therapeutic purpose without gene
      correction.

PMID- 30206204
TI  - Transcription coactivator Cited1 acts as an inducer of trophoblast-like state
      from mouse embryonic stem cells through the activation of BMP signaling.
AB  - Trophoblast lineages, precursors of the placenta, are essential for post
      implantation embryo survival. However, the regulatory network of trophoblast
      development remains incompletely understood. Here, we report that Cited1, a
      transcription coactivator, is a robust inducer for trophoblast-like state from
      mouse embryonic stem cells (ESCs). Depletion of Cited1 in ESCs compromises the
      trophoblast lineage specification induced by BMP signaling. In contrast,
      overexpression of Cited1 in ESCs induces a trophoblast-like state with elevated
      expression of trophoblast marker genes in vitro and generation of trophoblastic
      tumors in vivo. Furthermore, global transcriptome profile analysis indicates that
      ectopic Cited1 activates a trophoblast-like transcriptional program in ESCs.
      Mechanistically, Cited1 interacts with Bmpr2 and Smad4 to activate the Cited1
      Bmpr2-Smad1/5/8 axis in the cytoplasm and Cited1-Smad4-p300 complexes in the
      nucleus, respectively. Collectively, our results show that Cited1 plays an
      important role in regulating trophoblast lineage specification through activating
      the BMP signaling pathway.

PMID- 30206205
TI  - TNFR2 unlocks a RIPK1 kinase activity-dependent mode of proinflammatory TNFR1
      signaling.
AB  - TNF is not only a major effector molecule of PAMP/DAMP-activated macrophages, but
      also regulates macrophage function and viability. We recently demonstrated that
      TNFR2 triggers necroptosis in macrophages with compromised caspase activity by
      two cooperating mechanisms: induction of endogenous TNF with subsequent
      stimulation of TNFR1 and depletion of cytosolic TRAF2-cIAP complexes. Here we
      show that TNFR2 activation in caspase-inhibited macrophages results in the
      production of endogenous TNF and TNFR1 stimulation followed by upregulation of
      A20, TRAF1, IL-6, and IL-1beta. Surprisingly, TNFR1-mediated induction of IL-6
      and IL-1beta was clearly evident in response to TNFR2 stimulation but occurred
      not or only weakly in macrophages selectively and directly stimulated via TNFR1.
      Moreover, TNFR2-induced TNFR1-mediated gene induction was largely inhibited by
      necrostatin-1, whereas upregulation of A20 and TRAF1 by direct and exclusive
      stimulation of TNFR1 remained unaffected by this compound. Thus, treatment with
      TNFR2/ZVAD enables TNFR1 in macrophages to stimulate gene induction via a pathway
      requiring RIPK1 kinase activity. TNFR2/ZVAD-induced production of IL-6 and IL
      1beta was largely blocked in necroptosis-resistant MLKL- and RIPK3-deficient
      macrophages, whereas induction of A20 and TRAF1 remained unaffected. In sum, our
      results show that in caspase-inhibited macrophages TNFR2 not only triggers
      TNF/TNFR1-mediated necroptosis but also TNF/TNFR1-mediated RIPK3/MLKL-dependent
      and -independent gene induction.

PMID- 30206206
TI  - MicroRNA-128a represses chondrocyte autophagy and exacerbates knee osteoarthritis
      by disrupting Atg12.
AB  - Chondrocyte loss is a prominent feature of osteoarthritis (OA). Autophagy is
      indispensable in maintaining the metabolic activities of cells exposed to
      deleterious stress. The contribution of microRNA signaling to chondrocyte
      autophagy in OA development remains elusive. We uncovered an association between
      poor autophagy and increased miR-128a expressions in articular chondrocytes of
      patients with end-stage knee OA and in a rat anterior cruciate ligament
      transection (ACLT) model for OA development. Cartilage matrix degradation and
      severe OA histopathology was evident upon forced miR-128a expression within the
      articular compartment. Intra-articular injections with miR-128a antisense
      oligonucleotide stabilized chondrocyte autophagy and slowed ACLT-mediated
      articular tissue destruction, including cartilage erosion, synovitis, osteophyte
      formation, and subchondral plate damage. In vitro, miR-128 signaling hindered
      Atg12 expression, LC3-II conversion, and autophagic puncta formation through
      targeting the 3'-untranslated region of Atg12. It increased apoptotic programs,
      diminishing cartilage formation capacity of articular chondrocytes. Inactivating
      histone methyltransferase EZH2 reduced methyl histone H3K27 enrichment in the miR
      128a promoter and upregulated miR-128a transcription in inflamed chondrocytes.
      Taken together, miR-128a-induced Atg12 loss repressed chondrocyte autophagy to
      aggravate OA progression. EZH2 inactivation caused H3K27 hypomethylation to
      accelerate miR-128a actions. Interruption of miR-128a signaling attenuated
      chondrocyte dysfunction and delayed OA development. Our data provide new insights
      into how miR-128a signaling affects chondrocyte survival and articular cartilage
      anabolism and highlight the potential of miR-128a targeting therapy to alleviate
      knee OA.

PMID- 30206207
TI  - Ceramide synthase-6 confers resistance to chemotherapy by binding to CD95/Fas in
      T-cell acute lymphoblastic leukemia.
AB  - Ceramide synthases (CERS) produce ceramides which are key intermediators in the
      biosynthesis of complex sphingolipids and play an important role in cell
      proliferation, differentiation, apoptosis and senescence. CERS6 is an isoform of
      ceramide synthases known to generate ceramides with C16 acyl chain (C16-Cer).
      CERS6 and C16-Cer levels were significantly higher in acute lymphoblastic
      leukemia (ALL) cells in comparison to peripheral blood mononuclear cells and T
      lymphocytes derived from healthy human volunteers. We investigated the role of
      CERS6 in chemo-resistance in T-ALL cell lines. Stable knockdown of CERS6 in CCRF
      CEM and MOLT-4 cells resulted in increased sensitivity to ABT-737, a pan-BCL-2
      inhibitor, while CCRF-CEM cells with exogenous CERS6 expression showed resistance
      to ABT-737 relative to the vector control. The cytotoxic activity of ABT-737 in
      CERS6 knockdown cells was significantly reduced by the addition of a caspase-8
      inhibitor Z-IETD, suggesting that CERS6 alters the cytotoxicity via extrinsic
      pathway of apoptosis. By co-immunoprecipitation of CERS6 in CCRF-CEM cells, we
      identified CD95/Fas, a mediator of extrinsic apoptotic pathway, as a novel CERS6
      binding partner. In Fas pull-down samples, FADD (Fas-associated protein with
      death domain) was detected at higher levels in cells with CERS6 knockdown
      compared with control cells when treated with ABT-737, and this was reversed by
      the overexpression of CERS6, demonstrating that CERS6 interferes with Fas-FADD
      DISC assembly. CERS6 may serve as a biomarker in determining the effectiveness of
      anticancer agents acting via the extrinsic pathway in T-ALL.

PMID- 30206208
TI  - EIF5A1 promotes trophoblast migration and invasion via ARAF-mediated activation
      of the integrin/ERK signaling pathway.
AB  - Trophoblast dysfunction is one mechanism implicated in the etiology of recurrent
      miscarriage (RM). Regulation of trophoblast function, however, is complex and the
      mechanisms contributing to dysregulation remain to be elucidated. Herein, we
      found EIF5A1 expression levels to be significantly decreased in cytotrophoblasts
      in RM villous tissues compared with healthy controls. Using the HTR-8/SVneo cell
      line as a model system, we found that overexpression of EIF5A1 promotes
      trophoblast proliferation, migration and invasion in vitro. Knockdown of EIF5A1
      or inhibiting its hypusination with N1-guanyl-1,7-diaminoheptane (GC7) suppresses
      these activities. Similarly, mutating EIF5A1 to EIF5A1K50A to prevent
      hypusination abolishes its effects on proliferation, migration and invasion.
      Furthermore, upregulation of EIF5A1 increases the outgrowth of trophoblasts in a
      villous explant culture model, whereas knockdown has the opposite effect.
      Suppression of EIF5A1 hypusination also inhibits the outgrowth of trophoblasts in
      explants. Mechanistically, ARAF mediates the regulation of trophoblast migration
      and invasion by EIF5A1. Hypusinated EIF5A1 regulates the integrin/ERK signaling
      pathway via controlling the translation of ARAF. ARAF level is also downregulated
      in trophoblasts of RM villous tissues and expression of ARAF is positively
      correlated with EIF5A1. Together, our results suggest that EIF5A1 may be a
      regulator of trophoblast function at the maternal-fetal interface and low levels
      of EIF5A1 and ARAF may be associated with RM.

PMID- 30206209
TI  - Regulation of cell surface protease receptor S100A10 by retinoic acid therapy in
      acute promyelocytic leukemia (APL)?.
AB  - S100A10 (p11), a member of the S100 family of small dimeric EF-hand-type Ca2+
      binding proteins, plays a role in a variety of both intracellular and
      extracellular processes. Previous studies have suggested that p11 is
      intrinsically unstable and requires binding to annexin A2 (p36) to prevent its
      rapid ubiquitylation and degradation. Our laboratory has shown that p11 levels
      are stimulated by the expression of the oncoprotein, PML/RARalpha. Furthermore,
      treatment of the APL cell line, NB4 with all-trans retinoic acid (ATRA) causes
      the rapid loss of p36 and p11 protein. However, the mechanism by which ATRA
      regulates p11 levels has not been established. Here, we show that the proteasomal
      inhibitor, lactacystin reversed the ATRA-dependent loss of p11, but did not cause
      an accumulation of ubiquitylated forms of p11, suggesting that ATRA promotes the
      proteasomal degradation of p11 in an ubiquitin-independent manner. ATRA treatment
      of MCF-7 breast cancer cells reduced p11 but not p36 transcript and protein
      levels, thus indicating that ATRA can regulate p11 levels independently of
      PML/RARalpha and p36. Overexpression of p36 upregulated p11 protein but not mRNA
      levels, indicating that p36 affects p11 post translationally. The forced
      expression of ubiquitin and p11 in 293 T cells resulted in ubiquitylation of p11
      that was blocked by mutagenesis of lysine 57. This study highlights the complex
      regulation of p11 by retinoid signaling and challenges the hypothesis that
      ubiquitin-mediated proteasomal degradation of p11 represents a universal
      mechanism of regulation of this protein.

PMID- 30206210
TI  - A live attenuated vaccine prevents replication and transmission of H7N9 highly
      pathogenic influenza viruses in mammals.
AB  - H7N9 influenza viruses emerged in 2013 and have caused severe disease and deaths
      in humans in China. Some H7N9 viruses circulating in chickens have mutated to
      highly pathogenic viruses that have caused several disease outbreaks in chickens.
      Studies have shown that when the H7N9 highly pathogenic viruses replicate in
      ferrets or humans, they easily acquire certain mammalian-adapting mutations and
      become highly lethal in mice and highly transmissible in ferrets by respiratory
      droplet, creating the potential for human-to-human transmission. Therefore, the
      development of effective control measures is a top priority for H7N9 pandemic
      preparedness. In this study, we evaluated the protective efficacy of a cold
      adapted, live attenuated H7N9 vaccine (H7N9/AAca) against two heterologous H7N9
      highly pathogenic viruses in mice and guinea pigs. Our results showed that one
      dose of the H7N9/AAca vaccine prevented disease and death in mice challenged with
      two different H7N9 highly pathogenic viruses, but did not prevent replication of
      the challenge viruses; after two doses of H7N9/AAca, the mice were completely
      protected from challenge with A/chicken/Hunan/S1220/2017(H7N9) virus, and very
      low viral titers were detected in mice challenged with H7N9 virus CK/SD008
      PB2/627 K. More importantly, we found that one dose of H7N9/AAca could
      efficiently prevent transmission of CK/SD008-PB2/627 K in guinea pigs. Our study
      suggests that H7N9/AAca has the potential to be an effective H7N9 vaccine and
      should be evaluated in humans.

PMID- 30206211
TI  - CDK4 inhibition diminishes p53 activation by MDM2 antagonists.
AB  - The genes encoding MDM2 and CDK4 are frequently co-amplified in sarcomas, and
      inhibitors to both targets are approved or clinically tested for therapy.
      However, we show that inhibitors of MDM2 and CDK4 antagonize each other in their
      cytotoxicity towards sarcoma cells. CDK4 inhibition attenuates the induction of
      p53-responsive genes upon MDM2 inhibition. Moreover, the p53 response was also
      attenuated when co-depleting MDM2 and CDK4 with siRNA, compared to MDM2 single
      knockdown. The complexes of p53 and MDM2, as well as CDK4 and Cyclin D1,
      physically associated with each other, suggesting direct regulation of p53 by
      CDK4. Interestingly, CDK4 inhibition did not reduce p53 binding or histone
      acetylation at promoters, but rather attenuated the subsequent recruitment of RNA
      Polymerase II. Taken together, our results suggest that caution must be used when
      considering combined CDK4 and MDM2 inhibition for patient treatment. Moreover,
      they uncover a hitherto unknown role for CDK4 and Cyclin D1 in sustaining p53
      activity.

PMID- 30206212
TI  - Melanoma cells resistant towards MAPK inhibitors exhibit reduced TAp73 expression
      mediating enhanced sensitivity to platinum-based drugs.
AB  - The efficacy of targeted MAPK signalling pathway inhibitors (MAPKi) in metastatic
      melanoma therapy is limited by the development of resistance mechanisms that
      results in disease relapse. This situation still requires treatment alternatives
      for melanoma patients with acquired resistance to targeted therapy. We found that
      melanoma cells, which developed resistance towards MAPKi show an enhanced
      susceptibility to platinum-based drugs, such as cisplatin and carboplatin. We
      found that this enhanced susceptibility inversely correlates with the expression
      level of the p53 family member TAp73. We show that the lower expression of the
      TAp73 isoform in MAPKi-resistant melanoma cells enhances accumulation of DNA
      double-strand breaks upon cisplatin and carboplatin treatment by reducing the
      efficiency of nucleotide excision repair. These data suggest that a subgroup of
      melanoma patients with acquired resistance to MAPKi treatment and low TAp73
      expression can benefit from chemotherapy with platinum-based drugs as a second
      line therapy.

PMID- 30206213
TI  - Identification of protein kinase inhibitors to reprogram breast cancer cells.
AB  - Direct reversion of cancers into normal-like tissues is an ideal strategy for
      cancer treatment. Recent reports have showed that defined transcription factors
      can induce reprogramming of cancer cells into pluripotent stem cells, supporting
      this notion. Here, we have developed a reprogramming method that uses a
      conceptually unique strategy for breast cancer cell treatment. We have screened a
      kinase inhibitor library and found that Rho-associated protein kinase (ROCK) and
      mammalian target of rapamycin (mTOR) kinase inhibitors can substitute for all
      transcription factors to be sufficient to reprogram breast cancer cells into
      progenitor cells. Furthermore, ROCK-mTOR inhibitors could reprogram breast cancer
      cells to another terminal lineage-adipogenic cells. Genome-wide transcriptional
      analysis shows that the induced fat-like cells have a profile different from
      breast cancer cells and similar to that of normal adipocytes. In vitro and in
      vivo tumorigenesis assays have shown that induced fat-like cells lose
      proliferation and tumorigenicity. Moreover, reprogramming treatment with ROCK
      mTOR inhibitors prevents breast cancer local recurrence in mice. Currently, ROCK
      mTOR inhibitors are already used as antitumor drugs in patients, thus, this
      reprogramming strategy has significant potential to move rapidly toward clinical
      trials for breast cancer treatment.

PMID- 30206214
TI  - Size-dependent loss of aboveground animals differentially affects grassland
      ecosystem coupling and functions.
AB  - Increasing evidence suggests that community-level responses to human-induced
      biodiversity loss start with a decrease of interactions among communities and
      between them and their abiotic environment. The structural and functional
      consequences of such interaction losses are poorly understood and have rarely
      been tested in real-world systems. Here, we analysed how 5 years of progressive,
      size-selective exclusion of large, medium, and small vertebrates and
      invertebrates-a realistic scenario of human-induced defaunation-impacts the
      strength of relationships between above- and belowground communities and their
      abiotic environment (hereafter ecosystem coupling) and how this relates to
      ecosystem functionality in grasslands. Exclusion of all vertebrates results in
      the greatest level of ecosystem coupling, while the additional loss of
      invertebrates leads to poorly coupled ecosystems. Consumer-driven changes in
      ecosystem functionality are positively related to changes in ecosystem coupling.
      Our results highlight the importance of invertebrate communities for maintaining
      ecological coupling and functioning in an increasingly defaunated world.

PMID- 30206215
TI  - TTK promotes mesenchymal signaling via multiple mechanisms in triple negative
      breast cancer.
AB  - Abnormal expression of TTK kinase has been associated with the initiation,
      progression, and therapeutic resistance of breast and other cancers, but its
      roles remain to be clarified. In this study, we examined the role of TTK in
      triple negative breast cancer (TNBC), and found that higher TTK expression
      correlated with mesenchymal and proliferative phenotypes in TNBC cells.
      Pharmacologic inhibition and genomic silencing of TTK not only reversed the
      epithelial-to-mesenchymal transition (EMT) in TNBC cells, but also increased the
      expression of KLF5, an effector of TGF-beta signaling and inhibitor of EMT. In
      addition, TTK inhibition decreased the expression of EMT-associated micro-RNA miR
      21 but increased the expression of miR-200 family members and suppressed TGF-beta
      signaling. To test if upregulation of KLF5 plays a role in TTK-induced EMT, TTK
      and KLF5 were silenced simultaneously, which reversed the decreased EMT caused by
      loss of TTK. Consistently, the decrease in miR-21 expression and increase in miR
      200 expression caused by TTK silencing were rescued by loss of KLF5. Altogether,
      this study highlights a novel role and signaling pathway for TTK in regulating
      EMT of TN breast cancer cells through TGF-beta and KLF5 signaling, highlighting
      targetable signaling pathways for TTK inhibitors in aggressive breast cancer.

PMID- 30206216
TI  - Gravimetry through non-linear optomechanics.
AB  - Precision gravimetry is key to a number of scientific and industrial
      applications, including climate change research, space exploration, geological
      surveys and fundamental investigations into the nature of gravity.  A variety of
      quantum systems, such as atom interferometry and on-chip-Bose-Einstein
      condensates have thus far been investigated to this aim. Here, we propose a new
      method which involves using a quantum optomechanical system for measurements of
      gravitational acceleration. As a proof-of-concept, we investigate the fundamental
      sensitivity for gravitational accelerometry of a cavity optomechanical system
      with a trilinear radiation pressure light-matter interaction. The phase of the
      optical output encodes the gravitational acceleration g and is the only component
      which needs to be measured. We prove analytically that homodyne detection is the
      optimal readout method and we predict an ideal fundamental sensitivity of Deltag
      = 10-15 ms-2 for state-of-the-art parameters of optomechanical systems, showing
      that they could, in principle, surpass the best atomic interferometers even for
      low optical intensities. Further, we show that the scheme is strikingly robust to
      the initial thermal state of the oscillator.

PMID- 30206217
TI  - The Type of Bariatric Surgery Impacts the Risk of Acute Pancreatitis: A
      Nationwide Study.
AB  - OBJECTIVE: We investigated whether vertical sleeve gastrectomy (VSG) and Roux-en
      Y gastric bypass surgery (RYGB) have a differential impact on post-operative risk
      of acute pancreatitis (AP). METHODS: This retrospective study uses the 2012-2014
      National Readmission Database. We compared morbidly obese patients who underwent
      VSG (n = 205,251), RYGB (n = 169,973), and hernia repair (HR) control (n =
      16,845). Our main outcome was rates of AP within 6 months post- vs. 6 months pre
      surgery in VSG, RYGB, and HR. We also investigated risk factors and outcomes of
      AP after bariatric surgery. RESULTS: The rates of AP increased post- vs. pre-VSG
      (0.21% vs. 0.04%; adjusted odds ratio [aOR] = 5.16, P < 0.05) and RYGB (0.17% vs.
      0.07%; aOR = 2.26, P < 0.05) but not post-HR. VSG was associated with a
      significantly greater increase in AP risk compared to RYGB (aOR = 2.28; 95% CI:
      1.10, 4.73). Furthermore, when compared to HR controls, only VSG was associated
      with a higher AP risk (aOR = 7.58; 95% CI: 2.09, 27.58). Developing AP within 6
      months following bariatric surgery was mainly associated with younger age (18-29
      years old: aOR = 3.76 for VSG and aOR: 6.40 for RYGB, P < 0.05) and gallstones
      (aOR = 85.1 for VSG and aOR = 46 for RYGB, P < 0.05). No patients developed
      "severe AP" following bariatric surgery. CONCLUSIONS: More patients develop AP
      within 6 months after VSG compared to RYGB and controls. This risk is highest for
      younger patients and those with gallstones. Prospective studies examining
      mechanisms and prevention are warranted.

PMID- 30206218
TI  - Reviving the Weizmann process for commercial n-butanol production.
AB  - Developing a commercial process for the biological production of n-butanol is
      challenging as it needs to combine high titer, yield, and productivities. Here we
      engineer Clostridium acetobutylicum to stably and continuously produce n-butanol
      on a mineral media with glucose as sole carbon source. We further design a
      continuous process for fermentation of high concentration glucose syrup using in
      situ extraction of alcohols by distillation under low pressure and high cell
      density cultures to increase the titer, yield, and productivity of n-butanol
      production to the level of 550 g/L, 0.35 g/g, and 14 g/L/hr, respectively. This
      process provides a mean to produce n-butanol at performance levels comparable to
      that of corn wet milling ethanol plants using yeast as a biocatalyst. It may hold
      the potential to be scaled-up at pilot and industrial levels for the commercial
      production of n-butanol.

PMID- 30206221
TI  - ARHGAP9 suppresses the migration and invasion of hepatocellular carcinoma cells
      through up-regulating FOXJ2/E-cadherin.
AB  - Rho GTPase activating protein 9 (ARHGAP9), a member of RhoGAP family, has been
      identified as a RhoGAP for Cdc42 and Rac1. Here, we aimed to clarify the
      expression and functional role of ARHGAP9 in hepatocellular carcinoma (HCC). By
      analyzing TCGA (The Cancer Genome Atlas) LIHC (liver hepatocellular carcinoma)
      database, we found that ARHGAP9 expression was lower in HCC tissues than in
      normal liver tissues, and that patients with ARHGAP9 lower expression had a
      significant shorter overall survival time than those with ARHGAP9 higher
      expression. Cell counting kit-8 (CCK-8), transwell assays and in vivo
      experimental lung metastasis assay revealed that ARHGAP9 overexpression could
      inhibit HCC cell proliferation, migration and invasion, as well as HCC lung
      metastases. By next-generation RNA-sequencing, we identified that a transcription
      factor, Forkhead Box J2 (FOXJ2), was significantly induced by ARHGAP9
      overexpression in HepG2 cells. Ectopic expression of FOXJ2 in HCC cell lines also
      exerted inhibitory effects on cell migration and invasion. Moreover, the
      inhibitory effects of ARHGAP9 on HCC cell migration and invasion was
      significantly attenuated by FOXJ2 knockdown. Luciferase reporter assay
      demonstrated that ARHGAP9 enhanced the transcription of E-cadherin (CDH1) via
      FOXJ2. Chromatin immunoprecipitation (ChIP) assay demonstrated that FOXJ2
      modulated the transcription of E-cadherin (CDH1) by directly binding to its
      promoter. Furthermore, Pearson's correlation analysis indicated that the mRNA
      levels of ARHGAP9 in HCC tissues were positively correlated with the mRNA levels
      of FOXJ2 and CDH1. These data clearly show that ARHGAP9/FOXJ2 inhibit cell
      migration and invasion during HCC development via inducing the transcription of
      CDH1.

PMID- 30206219
TI  - Phosphoproteomic-based kinase profiling early in influenza virus infection
      identifies GRK2 as antiviral drug target.
AB  - Although annual influenza epidemics affect around 10% of the global population,
      current treatment options are limited and development of new antivirals is
      needed. Here, using quantitative phosphoproteomics, we reveal the unique
      phosphoproteome dynamics that occur in the host cell within minutes of influenza
      A virus (IAV) infection. We uncover cellular kinases required for the observed
      signaling pattern and find that inhibition of selected candidates, such as the G
      protein-coupled receptor kinase 2 (GRK2), leads to decreased IAV replication. As
      GRK2 has emerged as drug target in heart disease, we focus on its role in IAV
      infection and show that it is required for viral uncoating. Replication of
      seasonal and pandemic IAVs is severely decreased by specific GRK2 inhibitors in
      primary human airway cultures and in mice. Our study reveals the IAV-induced
      changes to the cellular phosphoproteome and identifies GRK2 as crucial node of
      the kinase network that enables IAV replication.

PMID- 30206220
TI  - Understanding 6th-century barbarian social organization and migration through
      paleogenomics.
AB  - Despite centuries of research, much about the barbarian migrations that took
      place between the fourth and sixth centuries in Europe remains hotly debated. To
      better understand this key era that marks the dawn of modern European societies,
      we obtained ancient genomic DNA from 63 samples from two cemeteries (from Hungary
      and Northern Italy) that have been previously associated with the Longobards, a
      barbarian people that ruled large parts of Italy for over 200 years after
      invading from Pannonia in 568 CE. Our dense cemetery-based sampling revealed that
      each cemetery was primarily organized around one large pedigree, suggesting that
      biological relationships played an important role in these early medieval
      societies. Moreover, we identified genetic structure in each cemetery involving
      at least two groups with different ancestry that were very distinct in terms of
      their funerary customs. Finally, our data are consistent with the proposed long
      distance migration from Pannonia to Northern Italy.

PMID- 30206223
TI  - GraphDDP: a graph-embedding approach to detect differentiation pathways in single
      cell-data using prior class knowledge.
AB  - Cell types can be characterized by expression profiles derived from single-cell
      RNA-seq. Subpopulations are identified via clustering, yielding intuitive
      outcomes that can be validated by marker genes. Clustering, however, implies a
      discretization that cannot capture the continuous nature of differentiation
      processes. One could give up the detection of subpopulations and directly
      estimate the differentiation process from cell profiles. A combination of both
      types of information, however, is preferable. Crucially, clusters can serve as
      anchor points of differentiation trajectories. Here we present GraphDDP, which
      integrates both viewpoints in an intuitive visualization. GraphDDP starts from a
      user-defined cluster assignment and then uses a force-based graph layout approach
      on two types of carefully constructed edges: one emphasizing cluster membership,
      the other, based on density gradients, emphasizing differentiation trajectories.
      We show on intestinal epithelial cells and myeloid progenitor data that GraphDDP
      allows the identification of differentiation pathways that cannot be easily
      detected by other approaches.

PMID- 30206222
TI  - Critical Southern Ocean climate model biases traced to atmospheric model cloud
      errors.
AB  - The Southern Ocean is a pivotal component of the global climate system yet it is
      poorly represented in climate models, with significant biases in upper-ocean
      temperatures, clouds and winds. Combining Atmospheric and Coupled Model Inter
      comparison Project (AMIP5/CMIP5) simulations, with observations and equilibrium
      heat budget theory, we show that across the CMIP5 ensemble variations in sea
      surface temperature biases in the 40-60 degrees S Southern Ocean are primarily
      caused by AMIP5 atmospheric model net surface flux bias variations, linked to
      cloud-related short-wave errors. Equilibration of the biases involves local
      coupled sea surface temperature bias feedbacks onto the surface heat flux
      components. In combination with wind feedbacks, these biases adversely modify
      upper-ocean thermal structure. Most AMIP5 atmospheric models that exhibit small
      net heat flux biases appear to achieve this through compensating errors. We
      demonstrate that targeted developments to cloud-related parameterisations provide
      a route to better represent the Southern Ocean in climate models and projections.

PMID- 30206224
TI  - Author Correction: Origin of large plasticity and multiscale effects in iron
      based metallic glasses.
AB  - The authors became aware of a mistake in the original version of this Article.
      Specifically, where discussing the Curie temperature of the amorphous phase, Tc,
      in the 'Thermal characterization' section of the Results and in Fig. 2, the
      authors should have been discussing the Curie temperature of the magnetic
      crystalline phases T'c. While the Curie temperature of the glass is lower than
      previously reported, this error does not affect the original discussion or
      conclusions of the Article. The authors apologize for the confusion caused by
      this mistake. In addition to this, there were errors in some of the equations in
      the main text, and the glass composition. A number of changes have been made in
      both the PDF and HTML versions of the Article to reflect these errors. A full
      list of these changes is available online.

PMID- 30206225
TI  - The Swr1 chromatin-remodeling complex prevents genome instability induced by
      replication fork progression defects.
AB  - Genome instability is associated with tumorigenesis. Here, we identify a role for
      the histone Htz1, which is deposited by the Swr1 chromatin-remodeling complex
      (SWR-C), in preventing genome instability in the absence of the replication
      fork/replication checkpoint proteins Mrc1, Csm3, or Tof1. When combined with
      deletion of SWR1 or HTZ1, deletion of MRC1, CSM3, or TOF1 or a replication
      defective mrc1 mutation causes synergistic increases in gross chromosomal
      rearrangement (GCR) rates, accumulation of a broad spectrum of GCRs, and
      hypersensitivity to replication stress. The double mutants have severe
      replication defects and accumulate aberrant replication intermediates. None of
      the individual mutations cause large increases in GCR rates; however, defects in
      MRC1, CSM3 or TOF1 cause activation of the DNA damage checkpoint and replication
      defects. We propose a model in which Htz1 deposition and retention in chromatin
      prevents transiently stalled replication forks that occur in mrc1, tof1, or csm3
      mutants from being converted to DNA double-strand breaks that trigger genome
      instability.

PMID- 30206226
TI  - Exome-wide analysis identifies three low-frequency missense variants associated
      with pancreatic cancer risk in Chinese populations.
AB  - Germline coding variants have not been systematically investigated for pancreatic
      ductal adenocarcinoma (PDAC). Here we report an exome-wide investigation using
      the Illumina Human Exome Beadchip with 943 PDAC cases and 3908 controls in the
      Chinese population, followed by two independent replicate samples including 2142
      cases and 4697 controls. We identify three low-frequency missense variants
      associated with the PDAC risk: rs34309238 in PKN1 (OR = 1.77, 95% CI: 1.48-2.12,
      P = 5.35 * 10-10), rs2242241 in DOK2 (OR = 1.85, 95% CI: 1.50-2.27, P = 4.34 * 10
      9), and rs183117027 in APOB (OR = 2.34, 95% CI: 1.72-3.16, P = 4.21 * 10-8).
      Functional analyses show that the PKN1 rs34309238 variant significantly increases
      the level of phosphorylated PKN1 and thus enhances PDAC cells' proliferation by
      phosphorylating and activating the FAK/PI3K/AKT pathway. These findings highlight
      the significance of coding variants in the development of PDAC and provide more
      insights into the prevention of this disease.

PMID- 30206227
TI  - The MYB/miR-130a/NDRG2 axis modulates tumor proliferation and metastatic
      potential in salivary adenoid cystic carcinoma.
AB  - Increasing evidence has emerged to suggest that N-myc downstream-regulated gene 2
      (NDRG2) dysregulation participates in a number of tumor biological processes.
      However, the role of NDRG2 and miRNA-mediated NDRG2 regulation in salivary
      adenoid cystic carcinoma (SACC) progression remain unknown. Here, we determined
      that SACC tissues exhibited decreased level of NDRG2, which was associated with
      poorer rates of overall survival and distant metastasis-free survival. Silencing
      NDRG2 promoted SACC cell proliferation and metastasis both in vitro and in vivo.
      MiRNAs have been reported as vital regulators of NDRG2 expression. Based on
      micronome sequencing of three paired samples of SACC and normal salivary gland
      tissue and on an online database analysis, miR-130a was identified as a candidate
      miRNA that potentially regulates NDRG2. We demonstrated that the expression level
      of NDRG2 was dramatically reduced by exogenous miR-130a. Moreover, a luciferase
      assay further validated that miR-130a could degrade NDRG2 mRNA by targeting sites
      in the NDRG2 3'UTR. A rescue experiment suggested that NDRG2 expression could
      reverse the miR-130a-mediated promotion of cell proliferation and invasion. The
      expression of miR-130a has been reported to be regulated by certain transcription
      factors. In the preset study, we verified that the transcription factor MYB acted
      as the critical driver in SACC-upregulated miR-130a expression directly and
      induced NDRG2 downregulation in SACC tissues. Additionally, MYB/miR-130a
      activated the STAT3 and AKT pathways by downregulating NDRG2. These observations
      suggest that the MYB/miR-130a/NDRG2 axis, which modulates proliferation and
      metastasis in SACC, provides promising targets for the treatment of SACC.

PMID- 30206228
TI  - Glutamic acid is a carrier for hydrazine during the biosyntheses of
      fosfazinomycin and kinamycin.
AB  - Fosfazinomycin and kinamycin are natural products that contain nitrogen-nitrogen
      (N-N) bonds but that are otherwise structurally unrelated. Despite their
      considerable structural differences, their biosynthetic gene clusters share a set
      of genes predicted to facilitate N-N bond formation. In this study, we show that
      for both compounds, one of the nitrogen atoms in the N-N bond originates from
      nitrous acid. Furthermore, we show that for both compounds, an acetylhydrazine
      biosynthetic synthon is generated first and then funneled via a glutamyl carrier
      into the respective biosynthetic pathways. Therefore, unlike other pathways to N
      N bond-containing natural products wherein the N-N bond is formed directly on a
      biosynthetic intermediate, during the biosyntheses of fosfazinomycin, kinamycin,
      and related compounds, the N-N bond is made in an independent pathway that forms
      a branch of a convergent route to structurally complex natural products.

PMID- 30206229
TI  - Gastric cancer mesenchymal stem cells derived IL-8 induces PD-L1 expression in
      gastric cancer cells via STAT3/mTOR-c-Myc signal axis.
AB  - The expression of PD-L1 in tumor cells is one of the main causes of tumor immune
      escape. However, the exact mechanism for regulating PD-L1 expression in gastric
      cancer (GC) cells remains unclear. Our previous studies have shown that
      mesenchymal stem cells (MSCs) exert broad immunosuppressive potential, modulating
      the activity of cells either in innate or adaptive immune system to promote tumor
      progress. This study aims to investigate whether GCMSCs regulate the PD-L1
      expression in GC cells and explore the specific molecular mechanism. The results
      have shown that GCMSCs enhanced PD-L1 expression in GC cells resulting in the
      resistance of GC cells to CD8+ T cells cytotoxicity. However, this resistance was
      attenuated with IL-8 inhibition. Further studies proved that IL-8 derived from
      GCMSCs induced PD-L1 expression in GC cells via c-Myc regulated by STAT3 and mTOR
      signaling pathways. Our data indicated that blocking IL-8 derived from GCMSCs may
      overcome the immune escape induced by PD-L1 in GC cells and provide a potential
      strategy to enhance the immunotherapy efficiency in GC.

PMID- 30206231
TI  - Generating inner ear organoids containing putative cochlear hair cells from human
      pluripotent stem cells.
AB  - In view of the prevalence of sensorineural hearing defects in an ageing
      population, the development of protocols to generate cochlear hair cells and
      their associated sensory neurons as tools to further our understanding of inner
      ear development are highly desirable. We report herein a robust protocol for the
      generation of both vestibular and cochlear hair cells from human pluripotent stem
      cells which represents an advance over currently available methods that have been
      reported to generate vestibular hair cells only. Generating otic organoids from
      human pluripotent stem cells using a three-dimensional culture system, we show
      formation of both types of sensory hair cells bearing stereociliary bundles with
      active mechano-sensory ion channels. These cells share many morphological
      characteristics with their in vivo counterparts during embryonic development of
      the cochlear and vestibular organs and moreover demonstrate electrophysiological
      activity detected through single-cell patch clamping. Collectively these data
      represent an advance in our ability to generate cells of an otic lineage and will
      be useful for building models of the sensory regions of the cochlea and
      vestibule.

PMID- 30206230
TI  - GWAS for Interleukin-1beta levels in gingival crevicular fluid identifies IL37
      variants in periodontal inflammation.
AB  - There is no agnostic GWAS evidence for the genetic control of IL-1beta expression
      in periodontal disease. Here we report a GWAS for "high" gingival crevicular
      fluid IL-1beta expression among 4910 European-American adults and identify
      association signals in the IL37 locus. rs3811046 at this locus (p = 3.3 * 10-22)
      is associated with severe chronic periodontitis (OR = 1.50; 95% CI = 1.12-2.00),
      10-year incident tooth loss (>=3 teeth: RR = 1.33; 95% CI = 1.09-1.62) and
      aggressive periodontitis (OR = 1.12; 95% CI = 1.01-1.26) in an independent sample
      of 4927 German/Dutch adults. The minor allele at rs3811046 is associated with
      increased expression of IL-1beta in periodontal tissue. In RAW macrophages, PBMCs
      and transgenic mice, the IL37 variant increases expression of IL-1beta and IL-6,
      inducing more severe periodontal disease, while IL-37 protein production is
      impaired and shows reduced cleavage by caspase-1. A second variant in the IL37
      locus (rs2708943, p = 4.2 * 10-7) associates with attenuated IL37 mRNA
      expression. Overall, we demonstrate that IL37 variants modulate the inflammatory
      cascade in periodontal disease.

PMID- 30206232
TI  - 3D micro-environment regulates NF-kappabeta dependent adhesion to induce monocyte
      differentiation.
AB  - Differentiation of monocytes entails their relocation from blood to the tissue,
      hence accompanied by an altered physicochemical micro-environment. While the
      mechanism by which the biochemical make-up of the micro-environment induces
      differentiation is known, the fluid-like to gel-like transition in the physical
      micro-environment is not well understood. Monocytes maintain non-adherent state
      to prevent differentiation. We establish that irrespective of the chemical
      makeup, a 3D gel-like micro-environment induces a positive-feedback loop of
      adhesion-MAPK-NF-kappabeta activation to facilitate differentiation. In 2D fluid
      like micro-environment, adhesion alone is capable of inducing differentiation via
      the same positive-feedback signaling. Chemical inducer treatment in fluid-like
      micro-environment, increases the propensity of monocyte adhesion via a brief
      pulse of p-MAPK. The adhesion subsequently elicit differentiation, establishing
      that adhesion is both necessary and sufficient to induce differentiation in 2D/3D
      micro-environment. MAPK, and NF-kappabeta being key molecules of multiple
      signaling pathways, we hypothesize that biochemically inert 3D gel-like micro
      environment would also influence other cellular functions.

PMID- 30206233
TI  - Large intrinsic anomalous Hall effect in half-metallic ferromagnet Co3Sn2S2 with
      magnetic Weyl fermions.
AB  - The origin of anomalous Hall effect (AHE) in magnetic materials is one of the
      most intriguing aspects in condensed matter physics and has been a controversial
      topic for a long time. Recent studies indicate that the intrinsic AHE is closely
      related to the Berry curvature of occupied electronic states. In a magnetic Weyl
      semimetal with broken time-reversal symmetry, there are significant contributions
      to Berry curvature around Weyl nodes, possibly leading to a large intrinsic AHE.
      Here, we report the quite large AHE in the half-metallic ferromagnet Co3Sn2S2
      single crystal. By systematically mapping out the electronic structure of
      Co3Sn2S2 both theoretically and experimentally, we demonstrate that the intrinsic
      AHE from the Weyl fermions near the Fermi energy is dominating. The intrinsic
      anomalous Hall conductivity depends linearly on the magnetization and can be
      reproduced by theoretical simulation, in which the Weyl nodes monotonically move
      with the constrained magnetic moment on Co atom.

PMID- 30206234
TI  - Inducing drop to bubble transformation via resonance in ultrasound.
AB  - Bubble formation plays an important role in industries concerned with mineral
      flotation, food, cosmetics, and materials, which requires additional energy to
      produce the liquid-gas interfaces. A naturally observed fact is, owing to the
      effect of surface tension, a bubble film tends to retract to reduce its surface
      area. Here we show a "reverse" phenomenon whereby a drop is transformed into a
      bubble using acoustic levitation via acoustic resonance. Once the volume of the
      cavity encapsulated by the buckled film reaches a critical value V*, resonance
      occurs and an abrupt inflation is triggered, leading to the formation of a closed
      bubble. Experiments and simulations both reveal that V* decreases with increasing
      acoustic frequency, which agrees well with acoustic resonance theory. The results
      afford enlightening insights into acoustic resonance and highlight its role in
      manipulating buckled fluid-fluid interfaces, providing a reference for
      fabricating unique core-shell-like materials.

PMID- 30206235
TI  - Mutant FUS causes DNA ligation defects to inhibit oxidative damage repair in
      Amyotrophic Lateral Sclerosis.
AB  - Genome damage and defective repair are etiologically linked to neurodegeneration.
      However, the specific mechanisms involved remain enigmatic. Here, we identify
      defects in DNA nick ligation and oxidative damage repair in a subset of
      amyotrophic lateral sclerosis (ALS) patients. These defects are caused by
      mutations in the RNA/DNA-binding protein FUS. In healthy neurons, FUS protects
      the genome by facilitating PARP1-dependent recruitment of XRCC1/DNA Ligase
      IIIalpha (LigIII) to oxidized genome sites and activating LigIII via direct
      interaction. We discover that loss of nuclear FUS caused DNA nick ligation
      defects in motor neurons due to reduced recruitment of XRCC1/LigIII to DNA strand
      breaks. Moreover, DNA ligation defects in ALS patient-derived iPSC lines carrying
      FUS mutations and in motor neurons generated therefrom are rescued by CRISPR/Cas9
      mediated correction of mutation. Our findings uncovered a pathway of defective
      DNA ligation in FUS-linked ALS and suggest that LigIII-targeted therapies may
      prevent or slow down disease progression.

PMID- 30206237
TI  - Chronic myeloid leukaemia cells require the bone morphogenic protein pathway for
      cell cycle progression and self-renewal.
AB  - Leukaemic stem cell (LSC) persistence remains a major obstacle to curing chronic
      myeloid leukaemia (CML). The bone morphogenic protein (BMP) pathway is
      deregulated in CML, with altered expression and response to the BMP ligands shown
      to impact on LSC expansion and behaviour. In this study, we determined whether
      alterations in the BMP pathway gene signature had any predictive value for
      therapeutic response by profiling 60 CML samples at diagnosis from the UK SPIRIT2
      trial and correlating the data to treatment response using the 18-month follow-up
      data. There was significant deregulation of several genes involved in the BMP
      pathway with ACV1C, INHBA, SMAD7, SNAIL1 and SMURF2 showing differential
      expression in relation to response. Therapeutic targeting of CML cells using BMP
      receptor inhibitors, in combination with tyrosine kinase inhibitor (TKI),
      indicate a synergistic mode of action. Furthermore, dual treatment resulted in
      altered cell cycle gene transcription and irreversible cell cycle arrest, along
      with increased apoptosis compared to single agents. Targeting CML CD34+ cells
      with BMP receptor inhibitors resulted in fewer cell divisions, reduced numbers of
      CD34+ cells and colony formation when compared to normal donor CD34+ cells, both
      in the presence and absence of BMP4. In an induced pluripotent stem cell (iPSC)
      model generated from CD34+ hematopoietic cells, we demonstrate altered cell cycle
      profiles and dynamics of ALK expression in CML-iPSCs in the presence and absence
      of BMP4 stimulation, when compared to normal iPSC. Moreover, dual targeting with
      TKI and BMP inhibitor prevented the self-renewal of CML-iPSC and increased meso
      endodermal differentiation. These findings indicate that transformed stem cells
      may be more reliant on BMP signalling than normal stem cells. These changes offer
      a therapeutic window in CML, with intervention using BMP inhibitors in
      combination with TKI having the potential to target LSC self-renewal and improve
      long-term outcome for patients.

PMID- 30206236
TI  - RecQL4-Aurora B kinase axis is essential for cellular proliferation, cell cycle
      progression, and mitotic integrity.
AB  - Human RecQL4 helicase plays critical roles in the maintenance of genomic
      stability. Mutations in RecQL4 helicase results in three clinically related
      autosomal recessive disorders: Rothmund-Thomson syndrome (RTS), RAPADILINO, and
      Baller-Gerold syndrome. In addition to several premature aging features, RTS
      patients are characterized by aneuploidy involving either loss or gain of a
      single chromosome. Chromosome mosaicism and isochromosomes involving chromosomes
      2, 7, and 8 have been reported in RecQL4-deficient RTS patients, but the precise
      role of RecQL4 in chromosome segregation/stability remains to be elucidated.
      Here, we demonstrate that RecQL4 physically and functionally interacts with
      Aurora B kinase (AURKB) and stabilizes its expression by inhibiting its
      ubiquitination process. Our study indicates that the N-terminus of RecQL4
      interacts with the catalytic domain of AURKB. Strikingly, RecQL4 suppression
      reduces the expression of AURKB leading to mitotic irregularities and apoptotic
      cell death. RecQL4 suppression increases the proportion of cells at the G2/M
      phase followed by an extensive cell death, presumably owing to the accumulation
      of mitotic irregularities. Both these defects (accumulation of cells at G2/M
      phase and an improper mitotic exit to sub-G1) are complemented by the ectopic
      expression of AURKB. Finally, evidence is provided for the requirement of both
      human telomerase reverse transcriptase and RecQL4 for stable immortalization and
      longevity of RTS fibroblasts. Collectively, our study suggests that the RecQL4
      AURKB axis is essential for cellular proliferation, cell cycle progression, and
      mitotic stability in human cells.

PMID- 30206238
TI  - Publisher Correction: The composition of the perinatal intestinal microbiota in
      cattle.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 30206239
TI  - Rapid detection of tetracycline resistance in bovine Pasteurella multocida
      isolates by MALDI Biotyper antibiotic susceptibility test rapid assay (MBT
      ASTRA).
AB  - Pasteurella multocida is notorious for its role as an opportunistic pathogen in
      infectious bronchopneumonia, the economically most important disease facing
      cattle industry and leading indication for antimicrobial therapy. To rationalize
      antimicrobial use, avoiding imprudent use of highly and critically important
      antimicrobials for human medicine, availability of a rapid antimicrobial
      susceptibility test is crucial. The objective of the present study was to design
      a MALDI Biotyper antibiotic susceptibility test rapid assay (MBT-ASTRA) procedure
      for tetracycline resistance detection in P. multocida. This procedure was
      validated on 100 clinical isolates with MIC-gradient strip test, and a comparison
      with disk diffusion was made. Sensitivity and specificity of the MBT-ASTRA
      procedure were 95.7% (95% confidence interval (CI) = 89.8-101.5) and 100% (95% CI
      = 100-100), respectively, classifying 98% of the isolates correctly after only
      three hours of incubation. Sensitivity and specificity of disk diffusion were
      93.5% (95% CI = 86.3-100.6) and 96.3% (95% CI = 91.3-101.3) respectively,
      classifying 95% of the isolates correctly. In conclusion, this MBT-ASTRA
      procedure has all the potential to fulfil the need for a rapid and highly
      accurate tetracycline susceptibility testing in P. multocida to rationalize
      antimicrobial use in outbreaks of bronchopneumonia in cattle or other clinical
      presentations across species.

PMID- 30206240
TI  - Neurotransmitter identity and electrophysiological phenotype are genetically
      coupled in midbrain dopaminergic neurons.
AB  - Most neuronal types have a well-identified electrical phenotype. It is now
      admitted that a same phenotype can be produced using multiple biophysical
      solutions defined by ion channel expression levels. This argues that systems
      level approaches are necessary to understand electrical phenotype genesis and
      stability. Midbrain dopaminergic (DA) neurons, although quite heterogeneous,
      exhibit a characteristic electrical phenotype. However, the quantitative genetic
      principles underlying this conserved phenotype remain unknown. Here we
      investigated the quantitative relationships between ion channels' gene expression
      levels in midbrain DA neurons using single-cell microfluidic qPCR. Using
      multivariate mutual information analysis to decipher high-dimensional statistical
      dependences, we unravel co-varying gene modules that link neurotransmitter
      identity and electrical phenotype. We also identify new segregating gene modules
      underlying the diversity of this neuronal population. We propose that the newly
      identified genetic coupling between neurotransmitter identity and ion channels
      may play a homeostatic role in maintaining the electrophysiological phenotype of
      midbrain DA neurons.

PMID- 30206241
TI  - Structures of Mycobacterium smegmatis 70S ribosomes in complex with HPF, tmRNA,
      and P-tRNA.
AB  - Ribosomes are the dynamic protein synthesis machineries of the cell. They may
      exist in different functional states in the cell. Therefore, it is essential to
      have structural information on these different functional states of ribosomes to
      understand their mechanism of action. Here, we present single particle cryo-EM
      reconstructions of the Mycobacterium smegmatis 70S ribosomes in the hibernating
      state (with HPF), trans-translating state (with tmRNA), and the P/P state (with P
      tRNA) resolved to 4.1, 12.5, and 3.4 A, respectively. A comparison of the P/P
      state with the hibernating state provides possible functional insights about the
      Mycobacteria-specific helix H54a rRNA segment. Interestingly, densities for all
      the four OB domains of bS1 protein is visible in the hibernating 70S ribosome
      displaying the molecular details of bS1-70S interactions. Our structural data
      shows a Mycobacteria-specific H54a-bS1 interaction which seems to prevent subunit
      dissociation and degradation during hibernation without the formation of 100S
      dimer. This indicates a new role of bS1 protein in 70S protection during
      hibernation in Mycobacteria in addition to its conserved function during
      translation initiation.

PMID- 30206243
TI  - Modeling clock-related metabolic syndrome due to conflicting light and food cues.
AB  - Most organisms possess a light- and food- entrainable circadian clock system
      enabling their adaptation to daily environmental changes in sunlight and food
      availability. The mammalian circadian system is composed of multiple clocks
      throughout the body. These local clocks are entrained by nutrient, neural,
      endocrine and temperature cues and drive diverse physiological functions
      including metabolism. In particular, the clock of the pancreatic beta cell
      rhythmically regulates the transcription of genes involved in glucose-stimulated
      insulin secretion. Perturbations of this fine-tuned oscillatory network increase
      the susceptibility to diseases. Besides chronic jet lag and shift work, common
      perturbations are ill-timed eating patterns which can lead to metabolic troubles
      (such as hypoinsulinemia). We have built a mathematical model describing the
      clock-dependent pancreatic regulation of glucose homeostasis in rodents. After
      calibrating the model using experimental data, we have investigated the effect of
      restricting food access to the normal rest phase. Our simulations show that the
      conflict between the light-dark cycle and the feeding-fasting cycle creates a
      differential phase shift in the expression of core clock genes (consistent with
      experimental observations). Our model further predicts that this induces a non
      concomitance between nutrient cues and clock-controlled cues driving metabolic
      outputs which results in hypoinsulinemia, hyperglycemia as well as in a loss of
      food anticipation.

PMID- 30206242
TI  - Variability in eukaryotic initiation factor iso4E in Brassica rapa influences
      interactions with the viral protein linked to the genome of Turnip mosaic virus.
AB  - Plant potyviruses require eukaryotic translation initiation factors (eIFs) such
      as eIF4E and eIF(iso)4E to replicate and spread. When Turnip mosaic virus (TuMV)
      infects a host plant, its viral protein linked to the genome (VPg) needs to
      interact with eIF4E or eIF(iso)4E to initiate translation. TuMV utilizes
      BraA.eIF4E.a, BraA.eIF4E.c, BraA.eIF(iso)4E.a, and BraA.eIF(iso)4E.c of Brassica
      rapa to initiate translation in Arabidopsis thaliana. In this study, the
      BraA.eIF4E.a, BraA.eIF4E.c, BraA.eIF(iso)4E.a, and BraA.eIF(iso)4E.c genes were
      cloned and sequenced from eight B. rapa lines, namely, two BraA.eIF4E.a alleles,
      four BraA.eIF4E.c alleles, four BraA.eIF(iso)4E.a alleles, and two
      BraA.eIF(iso)4E.c alleles. Yeast two-hybrid (Y2H) and bimolecular fluorescence
      complementation (BiFC) analyses indicated that TuMV VPg could not interact with
      eIF4E, but only with eIF(iso)4E of B. rapa. In addition, the VPgs of the
      different TuMV isolates interacted with various eIF(iso)4E copies in B. rapa. In
      particular, TuMV-UK1/CDN1 VPg only interacted with BraA.eIF(iso)4E.c, not with
      BraA.eIF(iso)4E.a. Some single nucleotide polymorphisms (SNPs) were identified
      that may have affected the interaction between eIF(iso)4E and VPg such as the SNP
      T106C in BraA.eIF(iso)4E.c and the SNP A154C in VPg. Furthermore, a three
      dimensional structural model of the BraA.eIF(iso)4E.c-1 protein was constructed
      to identify the specific conformation of the variable amino acids from
      BraA.eIF(iso)4E.c. The 36th amino acid in BraA.eIF(iso)4E.c is highly conserved
      and may play an important role in establishing protein structural stability. The
      findings of the present study may lay the foundation for future investigations on
      the co-evolution of TuMV and eIF(iso)4E.

PMID- 30206244
TI  - Raman imaging as a new approach to identification of the mayenite group minerals.
AB  - The mayenite group includes minerals with common formula Ca12Al14O32-x(OH)3x[W6
      3x], where W = F, Cl, OH, H2O and x = 0-2. This distinction in the composition is
      associated with W site which may remain unoccupied or be occupied by negatively
      charged ions: OH-, F-, Cl-, as well as neutral molecules like H2O. However, there
      is no experimental approach to easily detect or differentiate mineral species
      within the mayenite group. Electron micro-beam facilities with energy- or
      wavelength-dispersive X-ray detectors, as most common tools in mineralogy, appear
      to be insufficient and do not provide a definite identification, especially, of
      hydroxylated or hydrated phases. Some solution provides typical Raman analysis
      ensuring identification of minerals and 3D Raman imaging as an innovative
      approach to distinguish various co-existing minerals of the mayenite group within
      a small area of the rock sample. Raman spectroscopy has also been successfully
      used for a determination of water type incorporated into the mineral structure as
      well as for a spatial distribution of phases by cluster approach analysis and/or
      integrated intensity analysis of bands in the hydroxyl region. In this study,
      Raman technique was for the first time used to reconstruct a 3D model of mayenite
      group mineral zonation, as well as to determine a way of water incorporation in
      the structure of these minerals. Moreover, for the first time, Raman data were
      correlated with alterations during the mineral-forming processes and used for
      reconstruction of the thermal history of studied rock. As a result, the influence
      of combustion gases has been proposed as a crucial factor responsible for the
      transformation between fluormayenite and fluorkyuygenite.

PMID- 30206245
TI  - Surface structures with unconventional patterns and shapes generated by
      femtosecond structured light fields.
AB  - We present an investigation on ultrashort laser surface structuring with
      structured light fields generated by various q-plates. In particular, q-plates
      with topological charges q = 1, 3/2, 2, 5/2 are used to generate femtosecond (fs)
      vector vortex beams, and form complex periodic surface structures through multi
      pulse ablation of a solid crystalline silicon target. We show how optical
      retardation tuning of the q-plate offers a feasible way to vary the fluence
      transverse distribution of the beam, thus allowing the production of structures
      with peculiar shapes, which depend on the value of q. The features of the
      generated surface structures are compared with the vector vortex beam
      characteristics at the focal plane, by rationalizing their relationship with the
      local state of the laser light. Our experimental findings demonstrate how
      irradiation with fs complex light beams can offer a valuable route to design
      unconventional surface structures.

PMID- 30206246
TI  - Interannual variability of leaf area index of an evergreen conifer stand was
      affected by carry-over effects from recent climate conditions.
AB  - Despite the relevance of leaf area index (LAI) to forest productivity, few
      studies have focused on the interannual variability of LAI of an evergreen stand
      and its relationship with stand growth and meteorological factors. We estimated
      the change in LAI of an evergreen conifer (Chamaecyparis obtusa) stand over 19
      years from a dataset using allometric methods. The LAI varied between 7.1 and 8.8
      m2 m-2, with a 95% confidence interval of <1.1 m2 m-2 over the 19 years. This LAI
      range was maintained such that the gradual increase in leaf area (LA) of the
      largest trees counterbalanced the gradual loss in LA of the smallest trees.
      Meanwhile, more trees showed a temporary decrease in LA in years with low summer
      precipitation. The LAI and current-year mean temperature for July and August
      (TJA) were weakly correlated, whereas the correlation coefficient increased (r =
      0.93) when LAI was correlated with the moving average TJA over the previous 6
      years, which agreed with the estimated turnover time of canopy foliage. The
      annual stem biomass growth rate was significantly positively correlated with
      summer precipitation, but not with LAI. These results will be useful for refining
      models in studies on forest growth and global climate change.

PMID- 30206247
TI  - Author Correction: Assessing the quality of supplementary sensory feedback using
      the crossmodal congruency task.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has not been fixed in the paper.

PMID- 30206248
TI  - Heterogeneous Catalytic Oxidation of Amides to Imides by Manganese Oxides.
AB  - Herein, we report a one-step peroxide mediated heterogeneous catalytic oxidation
      of amides to imides utilizing a series of manganese oxides. Among them, Cs/Mn2O3
      was found to be the most active catalyst for the selective partial oxidation of N
      benzylbenzamide to diphenyl imide. We have been able to apply an optimized
      oxidation method to other aromatic substrates. The feasibility of using air as an
      oxidant, the heterogeneous nature, inexpensive catalytic materials, respectable
      turnover numbers, and chemoselectivity to imides make this methodology an
      attractive choice for functional group transformations of amides to imides.

PMID- 30206249
TI  - Small membranous proteins of the TorE/NapE family, crutches for cognate
      respiratory systems in Proteobacteria.
AB  - In this report, we investigate small proteins involved in bacterial alternative
      respiratory systems that improve the enzymatic efficiency through better
      anchorage and multimerization of membrane components. Using the small protein
      TorE of the respiratory TMAO reductase system as a model, we discovered that TorE
      is part of a subfamily of small proteins that are present in proteobacteria in
      which they play a similar role for bacterial respiratory systems. We reveal by
      microscopy that, in Shewanella oneidensis MR1, alternative respiratory systems
      are evenly distributed in the membrane contrary to what has been described for
      Escherichia coli. Thus, the better efficiency of the respiratory systems observed
      in the presence of the small proteins is not due to a specific localization in
      the membrane, but rather to the formation of membranous complexes formed by TorE
      homologs with their c-type cytochrome partner protein. By an in vivo approach
      combining Clear Native electrophoresis and fluorescent translational fusions, we
      determined the 4:4 stoichiometry of the complexes. In addition, mild
      solubilization of the cytochrome indicates that the presence of the small protein
      reinforces its anchoring to the membrane. Therefore, assembly of the complex
      induced by this small protein improves the efficiency of the respiratory system.

PMID- 30206250
TI  - Ghrelin expression is associated with a favorable outcome in male breast cancer.
AB  - Ghrelin and obestatin are two gastrointestinal peptides, derived from a common
      precursor. Expression of both peptides have been found in breast cancer tissue
      and ghrelin has been associated with breast cancer development. Ghrelin
      expression is associated with longer survival in women diagnosed with invasive
      and node negative breast cancer. The clinical implications of the peptide
      expression in male breast cancer are unclear. The aim of this study was to
      investigate the role and potential clinical value of ghrelin and obestatin in
      male breast cancer. A tissue microarray of invasive male breast cancer specimens
      from 197 patients was immunostained with antibodies versus the two peptides. The
      expression of the peptides was correlated to previously known prognostic factors
      in breast cancer and to the outcome. No strong correlations were found between
      ghrelin or obestatin expression and other known prognostic factors. Only ghrelin
      expression was statistically significantly correlated to breast cancer-specific
      survival (HR 0.39, 95% CI 0.18-0.83) in univariate analyses and in multivariate
      models, adjusted for tumor size and node status (HR 0.38, 95% CI 0.17-0.87). HR
      for obestatin was 0.38 (95% CI 0.11-1.24). Ghrelin is a potential prognostic
      factor for breast cancer death in male breast cancer. Patients with tumors
      expressing ghrelin have a 2.5-fold lower risk for breast cancer death than those
      lacking ghrelin expression. Drugs targeting ghrelin are currently being
      investigated in clinical studies treating metabolic or nutritional disorders.
      Ghrelin should be further evaluated in forthcoming studies as a prognostic marker
      with the aim to be included in decision algorithms.

PMID- 30206252
TI  - Burkholderia pseudomallei-loaded cells act as a Trojan horse to invade the brain
      during endotoxemia.
AB  - Neurologic melioidosis occurs in both human and animals; however, the mechanism
      by which the pathogen Burkholderia pseudomallei invades the central nervous
      system (CNS) remains unclear. B. pseudomallei-loaded Ly6C cells have been
      suggested as a putative portal; however, during melioidosis, lipopolysaccharide
      (LPS) can drive disruption of the blood-brain barrier (BBB). This study aims to
      test whether the Trojan horse-like mechanism occurs during endotoxemia. The
      expression levels of cerebral cytokines, chemokines and cell adhesion molecules;
      the activation of astrocytes, microglia and endothelial cells; and the increased
      vascular permeability and brain-infiltrating leukocytes were evaluated using B.
      pseudomallei, B. thailandensis, B. cenocepacia and B. multivorans LPS-induced
      brains. Accordingly, different degrees of BBB damage in those brains with
      endotoxemia were established. The B. multivorans LPS-induced brain exhibited the
      highest levels of disruptive BBB according to the above mediators/indicators.
      Into these distinct groups of endotoxemic mice, B. pseudomallei-loaded Ly6C cells
      or free B. pseudomallei were adoptively transferred at equal bacterial
      concentrations (103 CFU). The bacterial load and number of cases of meningeal
      neutrophil infiltration in the brains of animals treated with B. pseudomallei
      loaded Ly6C cells were higher than those in brains induced by free B.
      pseudomallei in any of the endotoxemic groups. In particular, these results were
      reproducible in B. multivorans LPS-induced brains. We suggest that B.
      pseudomallei-loaded cells can act as a Trojan horse and are more effective than
      free B. pseudomallei in invading the CNS under septic or endotoxemic conditions
      even when there is a high degree of BBB disruption.

PMID- 30206253
TI  - A flexible high speed pulse chopper system for an inverted neutron time-of-flight
      option on backscattering spectrometers.
AB  - We present the design and simulation of a high resolution inverted time-of-flight
      option for a neutron spectrometer with crystal analysers in backscattering, with
      specific reference to the IN16B spectrometer at the Institut Laue-Langevin,
      Grenoble. While the conventional configuration with Si 111 crystals provides sub
      MUeV resolution in an energy range limited to +/-30 MUeV, the novel BATS option
      (BATS: Backscattering and Time-of-flight Spectrometer) extends the energy window
      to 340 MUeV with only a slightly increased resolution of 1.2 MUeV. Moreover, the
      observation window can be shifted to inelastic energy transfers. To bring this
      about, a novel fast chopper system with disks of large diameter and complex slit
      pattern is used, offering high flexibility in resolution and repetition rate. The
      chopper system consists out of two counter rotating disk chopper pairs. It
      provides 7 different pulse lengths, three pulse repetition rates up to 237 Hz and
      can operate with Si 111 or Si 311 crystal analysers. The latter option is a
      unique feature which covers a Q-range up to 3.7 A-1 with a resolution of 6.8
      MUeV. Extensive ray-tracing simulations have been used to validate the design of
      the pulse chopper system, set limits on the sample size, and assess the
      achievable energy resolutions of the different chopper configurations.

PMID- 30206251
TI  - ADAP1 limits neonatal cardiomyocyte hypertrophy by reducing integrin cell surface
      expression.
AB  - The ArfGAP with dual PH domains 1 (ADAP1) regulates the activation of the
      hypertrophic mitogen-activated protein kinase ERK1/2 pathway in non
      cardiomyocytes. However, its role in cardiomyocytes is unknown. Our aim was to
      characterize the role of ADAP1 in the hypertrophic process of cardiomyocytes. We
      assessed the expression of ADAP1 in the hearts of adult and neonatal rats by RT
      qPCR and Western blotting and showed that it is preferentially expressed in
      cardiomyocytes. Adenoviral-mediated ADAP1 overexpression in cultured rat neonatal
      ventricular cardiomyocytes limited their serum-induced hypertrophic response as
      measured by immunofluorescence microscopy. Furthermore, ADAP1 overexpression
      completely blocked phenylephrine- and Mek1 constitutively active (Mek1ca) mutant
      induced hypertrophy in these cells. The anti-hypertrophic effect of ADAP1 was not
      caused by a reduction in protein synthesis, interference with the Erk1/2 pathway,
      or disruption of the fetal gene program activation, as assessed by nascent
      protein labeling, Western blotting, and RT-qPCR, respectively. An analysis of
      cultured cardiomyocytes by confocal microscopy revealed that ADAP1 partially re
      organizes alpha-actinin into dense puncta, a phenomenon that is synergized by
      Mek1ca overexpression. Biotin labeling of cell surface proteins from
      cardiomyocytes overexpressing ADAP1 revealed that it reduces the surface
      expression of beta1-integrin, an effect that is strongly potentiated by Mek1ca
      overexpression. Our findings provide insights into the anti-hypertrophic function
      of ADAP1 in cardiomyocytes.

PMID- 30206254
TI  - Macrofungal species distributions depend on habitat partitioning of topography,
      light, and vegetation in a temperate mountain forest.
AB  - The habitat partitioning hypothesis provides a conceptual framework for
      explaining the maintenance of plant and animal diversity. Its central tenet
      assumes environmental conditions are spatially structured, and that this
      structure is reflected in species distributions through associations with
      different habitats. Studies confirming habitat partitioning effects have focused
      primarily on spatial distributions of plants and animals, with habitat
      partitioning hypothesis under explored for macrofungi. Here, we examined the
      sporocarps of macrofungi in a 5-ha forest dynamics plot in China. We used four
      different methods to define microhabitats for habitat partitioning analyses based
      on topography, understory light availability, plant community, or a combination
      of these factors, and analyzed the effect of microhabitat partitioning on
      epigeous macrofungal community. Our results showed that the characteristics of
      the macrofungal assemblages varied among the habitats. A total of 85 species
      examined were associated with one or more of the habitat types (85/125, 68%). The
      factors related to the sporocarp composition differed among the various
      microhabitats. Our findings suggest that different microhabitats favor occurrence
      of different macrofungal species, and sporocarps -environment relation varied
      among the different microhabitats at this temperate mountain forest locality.
      These findings shed new light to the biodiversity conservation in macrofungi in
      temperate deciduous broad-leaved forest and point to the potential importance of
      microhabitat partitioning for sporocarp formation.

PMID- 30206256
TI  - On the Stability of MHD Boundary Layer Flow over a Stretching/Shrinking Wedge.
AB  - The steady two dimensional magnetohydrodynamic (MHD) boundary layer flow and heat
      transfer over a stretching/shrinking permeable wedge is numerically investigated.
      The partial differential equations governing the flow and heat transfer are
      transformed into a system of ordinary differential equations using a similarity
      transformation. These equations are then solved numerically using the boundary
      value problem solver, bvp4c in Matlab software. It is found that dual solutions
      exist for a certain range of the shrinking strength. A stability analysis is
      performed to identify which solution is stable and physically reliable.

PMID- 30206255
TI  - Electrophysiological Correlates of Blast-Wave Induced Cerebellar Injury.
AB  - Understanding the mechanisms underlying traumatic neural injury and the sequelae
      of events in the acute phase is important for deciding on the best window of
      therapeutic intervention. We hypothesized that evoked potentials (EP) recorded
      from the cerebellar cortex can detect mild levels of neural trauma and provide a
      qualitative assessment tool for progression of cerebellar injury in time. The
      cerebellar local field potentials evoked by a mechanical tap on the hand and
      collected with chronically implanted micro-ECoG arrays on the rat cerebellar
      cortex demonstrated substantial changes both in amplitude and timing as a result
      of blast-wave induced injury. The results revealed that the largest EP changes
      occurred within the first day of injury, and partial recoveries were observed
      from day-1 to day-3, followed by a period of gradual improvements (day-7 to day
      14). The mossy fiber (MF) and climbing fiber (CF) mediated components of the EPs
      were affected differentially. The behavioral tests (ladder rung walking) and
      immunohistological analysis (calbindin and caspase-3) did not reveal any
      detectable changes at these blast pressures that are typically considered as mild
      (100-130 kPa). The results demonstrate the sensitivity of the
      electrophysiological method and its use as a tool to monitor the progression of
      cerebellar injuries in longitudinal animal studies.

PMID- 30206258
TI  - Effect of present versus previous smoking on non-invasive haemodynamics.
AB  - We examined cardiovascular function in 637 volunteers (19-72 years) without
      antihypertensive medication in never smokers (n = 365), present smokers (n = 81)
      and previous smokers (n = 191, median abstinence 10 years). Haemodynamics during
      passive head-up tilt were recorded using whole-body impedance cardiography and
      radial pulse wave analysis. Results were adjusted for age, sex, body mass index,
      LDL cholesterol and alcohol use. Systolic and diastolic blood pressure, heart
      rate, and pulse wave velocity were not different between the groups. Supine
      aortic reflection times did not differ, while upright values were shorter in
      present versus previous smokers (p = 0.04). Heart rate adjusted augmentation
      index was increased in the supine position in present smokers versus controls (p
      = 0.045), and in present (p < 0.001) and previous (p = 0.031) smokers versus
      controls in the upright position. Supine and upright cardiac output was higher (p
      <= 0.016) and systemic vascular resistance lower (p <= 0.001) in present versus
      previous smokers. In spite of the long abstinence, in the upright position
      previous smokers had lower cardiac output (p = 0.032) and higher systemic
      vascular resistance (p = 0.014) than never smokers. In the absence of differences
      in blood pressure and arterial stiffness, present smokers presented with
      hyperdynamic circulation and enhanced wave reflection compared with previous
      smokers.

PMID- 30206257
TI  - The critical role of amygdala subnuclei in nociceptive and depressive-like
      behaviors in peripheral neuropathy.
AB  - The amygdala is an important component of the limbic system that participates in
      the control of the pain response and modulates the affective-motivational aspect
      of pain. Neuropathic pain is a serious public health problem and has a strong
      affective-motivational component that makes it difficult to treat. The central
      (CeA), basolateral (BLA) and lateral (LA) nuclei of the amygdala are involved in
      the processing and regulation of chronic pain. However, the roles of these nuclei
      in the maintenance of neuropathic pain, anxiety and depression remain unclear.
      Thus, the main objective of this study was to investigate the role of amygdala
      subnuclei in the modulation of neuropathic pain, including the affective
      motivational axis, in an experimental model of peripheral neuropathy. The
      specific goals were as follows: (1) To evaluate the nociceptive responses and the
      patterns of activation of the CeA, BLA and LA in neuropathic rats; and (2) To
      evaluate the effect of inactivating the amygdala nuclei on the nociceptive
      response, anxiety and depressive behaviors, motor activity, and plasma stress
      hormones in animals with neuropathic pain. Thus, mechanical hyperalgesia and
      allodynia, and the pattern of c-Fos staining in the amygdala subnuclei were
      evaluated in rats with chronic constriction of the sciatic nerve, as well as sham
      operated and naive rats. Once the amygdala subnuclei involved in neuropathic pain
      response were defined, those subnuclei were pharmacological inactivated. The
      effect of muscimol inactivation on the nociceptive response (hyperalgesia and
      allodynia), anxiety (elevated plus-maze), depressive-like behavior (forced swim
      test), motor activity (open field), and plasma stress hormone levels
      (corticosterone and adrenocorticotropic hormone) were evaluated in sham-operated
      and neuropathic animals. The results showed that the anterior and posterior
      portions of the BLA and the central portion of the CeA are involved in
      controlling neuropathic pain. The inactivation of these nuclei reversed
      hyperalgesia, allodynia and depressive-like behavior in animals with peripheral
      neuropathy. Taken together, our findings improve our understanding of the
      neurocircuitry involved in persistent pain and the roles of specific amygdala
      subnuclei in the modulation of neuropathic pain, including the neurocircuitry
      that processes the affective-motivational component of pain.

PMID- 30206260
TI  - Tuning electronic properties of transition-metal dichalcogenides via defect
      charge.
AB  - Defect engineering is a promising route for controlling the electronic properties
      of monolayer transition-metal dichalcogenide (TMD) materials. Here, we
      demonstrate that the electronic structure of MoS2 depends sensitively on the
      defect charge, both its sign and magnitude. In particular, we study shallow bound
      states induced by charged defects using large-scale tight-binding simulations
      with screened defect potentials and observe qualitative changes in the orbital
      character of the lowest lying impurity states as function of the impurity charge.
      To gain further insights, we analyze the competition of impurity states
      originating from different valleys of the TMD band structure using effective mass
      theory and find that impurity state binding energies are controlled by the
      effective mass of the corresponding valley, but with significant deviations from
      hydrogenic behaviour due to unconventional screening of the defect potential.

PMID- 30206261
TI  - Partial Shocks on Cooperative Multiplex Networks with Varying Degrees of Noise.
AB  - In many cooperative networks, such as alliance and trade networks, abrupt and
      intense changes to the state of the system (which we call "shocks"), can
      substantially change the network. We examine how such shocks affect multiplex
      networks via an agent-based model, in which agents add, drop, or change ties to
      increase their utility. At a certain time-point, some agents are "shocked" by
      changing (increasing or decreasing) the cost associated with tie-formation or tie
      maintenance. Our model makes several improvements to previous models, including
      (a) only a fraction of nodes are shocked to simulate small wars or scattered
      tariff increases or decreases and (b) agents can make both utility-maximizing
      decisions and randomly rewire ties to explore the utility landscape.
      Interestingly, we find that randomly rewiring ties increases the utility of
      agents, for reasons similar to simulated annealing in physics. Furthermore, we
      create a novel metric to determine how networks change after a shock and find
      that the size of a shock and noise significantly changes the network, but only
      when agents' incentives for tie-formation are sufficiently high. Together, these
      results suggest that adding more realism to cooperation network models can give
      nuanced understanding to network shocks.

PMID- 30206259
TI  - Three-dimensional motion analysis for comprehensive understanding of gait
      characteristics after sciatic nerve lesion in rodents.
AB  - Rodent models of sciatic nerve lesion are regularly used to assess functional
      deficits in nerves. Impaired locomotor functions induced by sciatic nerve lesion
      are currently evaluated with scoring systems despite their limitations. To
      overcome these shortcomings, which includes low sensitivity, little significance,
      and the representation of only marginal components of motion profiles, some
      additional metrics have been introduced. However, a quantitative determination of
      motion deficits is yet to be established. We used a three-dimensional motion
      analysis to investigate gait deficits after sciatic nerve lesion in rats. This
      enabled us to depict the distorted gait motion using both traditional parameters
      and novel readouts that are specific for the three-dimensional analysis. Our
      results suggest that three-dimensional motion analysis facilitates a
      comprehensive understanding of the gait impairment specifically, but not limited
      to, a sciatic lesion rat model. A broad application of these methods will improve
      understanding and standardized motor assessment.

PMID- 30206262
TI  - Construction of controlled-NOT gate based on microwave-activated phase (MAP) gate
      in two transmon system.
AB  - We experimentally constructed an all-microwave scheme for the controlled-NOT
      (cNOT) gate between two superconducting transmon qubits in a three dimensional
      cavity. Our cNOT gate is based on the microwave-activated phase (MAP) gate, which
      requires an additional procedure to compensate the accumulated phases during the
      operation of the MAP gate. We applied Z-axis phase gates using microwave
      hyperbolic secant pulse on both qubits with adequate rotation angles
      systematically calibrated by separate measurements. We evaluated the gate
      performance of the constructed cNOT gate by performing two-qubit quantum process
      tomography (QPT). Finally, we present the experimental implementation of the
      Deutsch-Jozsa algorithm using the cNOT gate.

PMID- 30206263
TI  - The voltage-dependence of MscL has dipolar and dielectric contributions and is
      governed by local intramembrane electric field.
AB  - Channels without canonical voltage sensors can be modulated by voltage acting on
      other domains. Here we show that besides protein dipoles, pore hydration can be
      affected by electric fields. In patches, both WT MscL and its V23T mutant show a
      decrease in the tension midpoint with hyperpolarization. The mutant exhibits a
      stronger parabolic dependence of transition energy on voltage, highly consistent
      with the favourable dielectric contribution from water filling the expanding
      pore. Purified V23T MscL in DPhPC droplet interface bilayers shows a similar
      voltage dependence. When reconstituted in an asymmetric DOPhPC/DPhPC bilayer
      carrying a permanent bias of ~130 mV due to a dipole potential difference between
      the interfaces, the channel behaved as if the local intramembrane electric field
      sets the tension threshold for gating rather than just the externally applied
      voltage. The data emphasize the roles of polarized water in the pore and
      interfacial lipid dipoles in channel gating thermodynamics.

PMID- 30206264
TI  - Hypoxia causes reductions in birth weight by altering maternal glucose and lipid
      metabolism.
AB  - Hypoxia of residence at high altitude (>2500 m) decreases birth weight. Lower
      birth weight associates with infant mortality and morbidity and increased
      susceptibility to later-in-life cardiovascular and metabolic diseases. We sought
      to determine the effects of hypoxia on maternal glucose and lipid metabolism and
      their contributions to fetal weight. C57BL6/NCrl mice, housed throughout
      gestation in normobaric hypoxia (15% oxygen) or normoxia, were studied at mid
      (E9.5) or late gestation (E17.5). Fetal weight at E17.5 was 7% lower under
      hypoxia than normoxia. The hypoxic compared with normoxic dams had ~20% less
      gonadal white adipose tissue at mid and late gestation. The hypoxic dams had
      better glucose tolerance and insulin sensitivity compared with normoxic dams and
      failed to develop insulin resistance in late gestation. They also had increased
      glucagon levels. Glucose uptake to most maternal tissues was ~2-fold greater in
      the hypoxic than normoxic dams. The alterations in maternal metabolism in hypoxia
      were associated with upregulation of hypoxia-inducible factor (HIF) target genes
      that serve, in turn, to increase glycolytic metabolism. We conclude that
      environmental hypoxia alters maternal metabolism by upregulating the HIF-pathway,
      and suggest that interventions that antagonize such changes in metabolism in high
      altitude pregnancy may be helpful for preserving fetal growth.

PMID- 30206265
TI  - Inhibition of Wnt/beta-catenin signaling suppresses myofibroblast differentiation
      of lung resident mesenchymal stem cells and pulmonary fibrosis.
AB  - An emerging paradigm proposes a crucial role for lung resident mesenchymal stem
      cells (LR-MSCs) via a fibroblastic transdifferentiation event in the pathogenesis
      of idiopathic pulmonary fibrosis (IPF). Aberrant activation of Wnt/beta-catenin
      signaling occurs in virtually all fibrotic lung diseases and is relevant to the
      differentiation of mesenchymal stem cells (MSCs). In vitro, by measuring the
      protein levels of several key components involved in Wnt/beta-catenin signaling,
      we confirmed that this signaling pathway was activated in the myofibroblast
      differentiation of LR-MSCs. Targeted inhibition of Wnt/beta-catenin signaling by
      a small molecule, ICG-001, dose-dependently impeded the proliferation and
      transforming growth factor-beta1 (TGF-beta1)-mediated fibrogenic actions of LR
      MSCs. In vivo, ICG-001 exerted its lung protective effects after bleomycin
      treatment through blocking mesenchymal-myofibroblast transition, repressing
      matrix gene expression, and reducing cell apoptosis. Moreover, delayed
      administration of ICG-001 attenuated bleomycin-induced lung fibrosis, which may
      present a promising therapeutic strategy for intervention of IPF. Interestingly,
      these antifibrotic actions of ICG-001 are operated by a mechanism independent of
      any disruption of Smad activation. In conclusion, our study demonstrated that
      Wnt/beta-catenin signaling may be an essential mechanism underlying the
      regulation of myofibroblast differentiation of LR-MSCs and their further
      participation in the development of pulmonary fibrosis.

PMID- 30206266
TI  - Visualisation and analysis of hepatitis C virus non-structural proteins using
      super-resolution microscopy.
AB  - Hepatitis C virus (HCV) RNA replication occurs in the cytosol of infected cells
      within a specialised membranous compartment. How the viral non-structural (NS)
      proteins are associated and organised within these structures remains poorly
      defined. We employed a super-resolution microscopy approach to visualise NS3 and
      NS5A in HCV infected cells. Using single molecule localisation microscopy, both
      NS proteins were resolved as clusters of localisations smaller than the
      diffraction-limited volume observed by wide-field. Analysis of the protein
      clusters identified a significant difference in size between the NS proteins. We
      also observed a reduction in NS5A cluster size following inhibition of RNA
      replication using daclatasvir, a phenotype which was maintained in the presence
      of the Y93H resistance associated substitution and not observed for NS3 clusters.
      These results provide insight into the NS protein organisation within hepatitis C
      virus RNA replication complexes and the mode of action of NS5A inhibitors.

PMID- 30206267
TI  - Tranexamic acid in primary total knee arthroplasty without tourniquet: a
      randomized, controlled trial of oral versus intravenous versus topical
      administration.
AB  - Abundant literature confirms that intravenous (IV) and intra-articular (IA)
      administration of tranexamic acid (TXA) reduces blood loss in total knee
      arthroplasty (TKA). Oral formulations of TXA exhibit profound cost-saving
      benefits. However, comparisons of the clinical efficacy among three different
      modalities of TXA administration have not been previously investigated in the
      setting of TKA with no closed suction drain and tourniquet. A total of 180
      patients undergoing TKA were randomized to receive 2-g oral TXA 2 hours
      preoperatively, 20-mg/kg IV TXA 5 minutes prior to incision, or 2-g IA TXA. The
      primary outcome was 72-hour blood loss. Secondary outcomes were reductions in
      hemoglobin, the rate of transfusions, and adverse events. No significant
      differences were identified with regard to the mean 72-hour blood loss among the
      three groups (1003 mL in oral group, 1108 mL in IV group, and 1059 mL in IA
      group, respectively). Similarly, hemoglobin reduction was equivalent among the
      groups. Only one patient in IV group exhibited deep venous thrombosis. No
      difference was identified regarding transfusion rates. Oral TXA results in
      similar blood loss in TKA, with a profound cost-saving benefit, compared with the
      IA and IV formulations.

PMID- 30206268
TI  - Nystatin-like Pseudonocardia polyene B1, a novel disaccharide-containing
      antifungal heptaene antibiotic.
AB  - Polyene macrolides such as nystatin A1 and amphotericin B belong to a large
      family of very valuable antifungal polyketide compounds typically produced by
      soil actinomycetes. Recently, nystatin-like Pseudonocardia polyene (NPP) A1 has
      been identified as a unique disaccharide-containing tetraene antifungal macrolide
      produced by Pseudonocardia autotrophica. Despite its significantly increased
      water solubility and decreased hemolytic activity, its antifungal activity
      remains limited compared with that of nystatin A1. In this study, we developed
      NPP B1, a novel NPP A1 derivative harboring a heptaene core structure, by
      introducing two amino acid substitutions in the putative NADPH-binding motif of
      the enoyl reductase domain in module 5 of the NPP A1 polyketide synthase NppC.
      The low level NPP B1 production yield was successfully improved by eliminating
      the native plasmid encoding a polyketide biosynthetic gene cluster present in P.
      autotrophica. In vitro and in vivo antifungal activity and toxicity studies
      indicated that NPP B1 exhibited comparable antifungal activity against Candida
      albicans and was less toxic than the most potent heptaene antifungal,
      amphotericin B. Moreover, NPP B1 showed improved pharmacokinetic parameters
      compared to those of amphotericin B, suggesting that NPP B1 could be a promising
      candidate for development into a pharmacokinetically improved and less-toxic
      polyene antifungal antibiotic.

PMID- 30206269
TI  - Efficient modulation of subwavelength focusing via meta-aperture-based plasmonic
      lens for multifunction applications.
AB  - Subwavelength focusing is crucial for many applications in photonics including
      super-resolution micro/nanoscopy, nanolithography, and optical trapping. However,
      most nanostructures exhibit poor ability to modulate focusing spot, which makes
      them hard to achieve ultra-small resolution. Here, we propose three kinds of
      plasmonic lens (PL) by utilizing different meta-aperture designs for efficient
      subwavelength focusing modulation. The shape of nanoaperture strongly influences
      the diffraction properties. Spatial modulation of focusing spot by employing a
      circular array of proposed nanoapertures is explored. The best focusing
      performance among these PLs is the design of T-shape nanoaperture, which has
      great resolution achieving ultra-small focusing spot of 0.14 lambda2 and 0.20
      lambda2 (lambda = 633 nm) for simulation and experiment respectively, better than
      lots of focusing devices especially by using linear polarization. Multiple-object
      trapping can be realized by using T-shape nanoaperture-based PL. Our designed PLs
      with different nanoapertures demonstrate the capability to broaden and integrate
      different functionalities for on-chip nanotechnologies development.

PMID- 30206270
TI  - Integrative effects of dystrophin loss on metabolic function of the mdx mouse.
AB  - Duchenne muscular dystrophy (DMD) is a disease marked by the development of
      skeletal muscle weakness and wasting. DMD results from mutations in the gene for
      the cytoskeletal protein dystrophin. The loss of dystrophin expression is not
      limited to muscle weakness but has multiple systemic consequences. Managing the
      nutritional requirements is an important aspect of the clinical care of DMD
      patients and is complicated by the poor understanding of the role of dystrophin,
      and dystrophic processes, in regulating metabolism. Here, we show that mdx mice,
      a genetic model of DMD, have significantly reduced fat mass relative to wild type
      C57BL/10. The alteration in body composition is independent of the presence of
      skeletal muscle disease, as it is still present in mice with transgenic
      expression of a fully-functional dystrophin in skeletal muscle. Furthermore, mdx
      mice do not increase their fat mass or body weight when housed under
      thermoneutral conditions, in marked contrast to C57BL/10 mice. We also
      demonstrated that mdx mice have significantly reduced fat metabolism and altered
      glucose uptake. These significant metabolic changes in dystrophic mice implicate
      dystrophin as an important regulator of metabolism. Understanding the metabolic
      functions of dystrophin is important for managing the nutritional needs of DMD
      patients.

PMID- 30206271
TI  - Independent adaptation mechanisms for numerosity and size perception provide
      evidence against a common sense of magnitude.
AB  - How numerical quantity is processed is a central issue for cognition. On the one
      hand the "number sense theory" claims that numerosity is perceived directly, and
      may represent an early precursor for acquisition of mathematical skills. On the
      other, the "theory of magnitude" notes that numerosity correlates with many
      continuous properties such as size and density, and may therefore not exist as an
      independent feature, but be part of a more general system of magnitude. In this
      study we examined interactions in sensitivity between numerosity and size
      perception. In a group of children, we measured psychophysically two sensory
      parameters: perceptual adaptation and discrimination thresholds for both size and
      numerosity. Neither discrimination thresholds nor adaptation strength for
      numerosity and size correlated across participants. This clear lack of
      correlation (confirmed by Bayesian analyses) suggests that numerosity and size
      interference effects are unlikely to reflect a shared sensory representation. We
      suggest these small interference effects may rather result from top-down
      phenomena occurring at late decisional levels rather than a primary "sense of
      magnitude".

PMID- 30206273
TI  - Transmission characteristics of all-dielectric guided-mode resonance filter in
      the THz region.
AB  - In this study we report the first on the terahertz (THz) transmission
      characteristics of a guided-mode resonance (GMR) filter made of all-dielectric
      material. Two strong transverse electric (TE) resonance modes, TE0,1 and TE1,1,
      and one strong transverse magnetic (TM) resonance mode, TM0,1, were detected. The
      measured resonances can be explained by diffraction from the grating surface of
      the GMR filter, and by guiding along the inside of the filter (slab waveguide).
      Because two identical GMR filters were employed to overcome limited grating
      numbers, the measured Q-factors of the TM0,1, TE1,1, and TM0,1 modes were as high
      as 62.9, 71.0, and 74.4 respectively. Also, we obtained polarization efficiencies
      of up to 96.9, 96.3, and 92.9% for the TM0,1, TM1,1, and TM0,1 modes,
      respectively, when the GMR filter was rotated to 90 degrees . By increasing the
      incident THz beam angle, one TE resonance can be divided into two TE resonances,
      and the resonant frequency can be adjusted like a THz tunable resonance filter.
      Furthermore, when the GMR filters were inserted between Teflon plates, only the
      TM1,1 mode was perfectly removed. The designed GMR filter has a high Q-factor,
      tunable filter, good polarizer, and good modulator characteristics. These
      experimental results were in good agreement with simulation results.

PMID- 30206272
TI  - Glucosylceramide modifies the LPS-induced inflammatory response in macrophages
      and the orientation of the LPS/TLR4 complex in silico.
AB  - Toll-like receptor 4 (TLR4) is activated by bacterial lipopolysaccharide (LPS),
      which drives the production of proinflammatory cytokines. Earlier studies have
      indicated that cholesterol- and glycosphingolipid-rich subregions of the plasma
      membrane (lipid domains) are important for TLR4-mediated signaling. We report
      that inhibition of glucosylceramide (GluCer) synthase, which resulted in
      decreased concentrations of the glycosphingolipid GluCer in lipid domains,
      reduced the LPS-induced inflammatory response in both mouse and human
      macrophages. Atomistic molecular dynamics simulations of the TLR4 dimer complex
      (with and without LPS in its MD-2 binding pockets) in membranes (in the presence
      and absence of GluCer) showed that: (1) LPS induced a tilted orientation of TLR4
      and increased dimer integrity; (2) GluCer did not affect the integrity of the
      LPS/TLR4 dimer but reduced the LPS-induced tilt; and (3) GluCer increased
      electrostatic interactions between the membrane and the TLR4 extracellular
      domain, which could potentially modulate the tilt. We also showed that GCS
      inhibition reduced the interaction between TLR4 and the intracellular adaptor
      protein Mal. We conclude that the GluCer-induced effects on LPS/TLR4 orientation
      may influence the signaling capabilities of the LPS/TLR4 complex by affecting its
      interaction with downstream signaling proteins.

PMID- 30206274
TI  - Cardiac magnetic resonance using late gadolinium enhancement and atrial T1
      mapping predicts poor outcome in patients with atrial fibrillation after catheter
      ablation therapy.
AB  - To determine the pre-procedural value of different fibrotic biomarkers and
      comprehensive cardiac magnetic resonance (CMR) for the prediction of poor
      response to ablation therapy in patients with atrial fibrillation (AF). Left
      atrial (LA) late gadolinium enhancement (LGE) and native LA T1 relaxation times
      were assessed using CMR. Plasma levels of relaxin, myeloperoxidase and serum
      levels of matrix metalloproteinase (MMP)-mediated cardiac specific titin
      fragmentation and MMP-mediated type IV collagen degradation were obtained. Poor
      outcome was defined by the recurrence of AF during 1-year follow-up. 61 patients
      were included in final analysis. Twenty (32.8%) patients had recurrence of AF.
      Patients with a recurrence of AF had a higher percentage of LA LGE (26.7 +/-
      12.5% vs. 17.0 +/- 7.7%; P < 0.001), higher LA T1 relaxation times (856.7 +/-
      112.2 ms vs. 746.8 +/- 91.0 ms; P < 0.001) and higher plasma levels of relaxin
      (0.69 +/- 1.34 pg/ml vs. 0.37 +/- 0.88 pg/ml; P = 0.035). In the multivariate Cox
      regression analysis, poor ablation outcome was best predicted by advanced LGE
      stage (hazard ratio (HR):5.487; P = 0.001) and T1 relaxation times (HR:1.007; P =
      0.001). Pre-procedural CMR is a valuable tool for prediction of poor response to
      catheter ablation therapy in patients with AF. It offers various imaging
      techniques for outcome prediction and might be valuable for a better patient
      selection prior to ablation therapy.

PMID- 30206275
TI  - Evolutionary trends and phylogenetic association of key morphological traits in
      the Italian rice varietal landscape.
AB  - Efficient germplasm exploitation in crop breeding requires comprehensive
      knowledge of the available genetic diversity. Linking molecular data to
      phenotypic expression is fundamental for the profitable utilisation of genetic
      resources. Italian rice germplasm is an invaluable source of genes, being
      characterised by marked heterogeneity. A phenotypic characterisation is presented
      in this paper, with a focus on the evolutionary trends, and on the comparison
      with available molecular studies. A panel of 351 Italian rice varieties was
      analysed using seven key morphological traits, employing univariate and
      multivariate analyses. Considerable variability was found, with clear
      morphological trends towards reduced plant height, earliness, and spindle-shaped
      caryopses. Previous findings indicating that genetic diversity was maintained
      throughout time could not be confirmed, as small phenotypic variability was found
      in the most recent rice varieties. Consistency with phylogenetic data from
      previous studies was partial: one phylogenetic subgroup was phenotypically well
      distinct, while the others had overlapping characteristics and encompassed a wide
      range of phenotypic variation. Our study provides a quantitative ready-to-use set
      of information to support new breeding programs, as well as the basis to develop
      variety-specific calibrations of eco-physiological models, to identify promising
      traits in light of climate change conditions and alternative management
      scenarios.

PMID- 30206276
TI  - Salt Bridge in Aqueous Solution: Strong Structural Motifs but Weak Enthalpic
      Effect.
AB  - Salt bridges are elementary motifs of protein secondary and tertiary structure
      and are commonly associated with structural driving force that increases
      stability. Often found on the interface to the solvent, they are highly
      susceptible to solvent-solute interactions, primarily with water but also with
      other cosolvents (especially ions). We have investigated the interplay of an
      Arginine-Aspartic acid salt bridge with simple salt ions in aqueous solution by
      means of molecular dynamics simulations. Besides structural and dynamical
      features at equilibrium, we have computed the mean force along the dissociation
      pathway of the salt bridge. We demonstrate that solvated ions influence the
      behavior of the salt bridge in a very specific and local way, namely the
      formation of tight ionic pairs Li+/Na+-Asp-. Moreover, our findings show that the
      enthalpic relevance of the salt bridge is minor, regardless of the presence of
      solvated ions.

PMID- 30206277
TI  - Identification of differentially methylated region (DMR) networks associated with
      progression of nonalcoholic fatty liver disease.
AB  - The progression of nonalcoholic fatty liver disease (NAFLD) is affected by
      epigenetics. We performed differentially methylated region (DMR) and co
      methylation analyses to identify DMR networks associated with the progression of
      NAFLD. DMRs displaying differences in multiple consecutive differentially
      methylated CpGs between mild and advanced NAFLD were extracted. The average
      values of topological overlap measures for the CpG matrix combining two different
      DMRs were calculated and two DMR networks that strongly correlated with the
      stages of fibrosis were identified. The annotated genes of one network included
      genes involved in transcriptional regulation, cytoskeleton organization, and
      cellular proliferation. The annotated genes of the second network were primarily
      associated with metabolic pathways. The CpG methylation levels in these networks
      were strongly affected by age and fasting plasma glucose levels, which may be
      important co-regulatory factors. The methylation status of five DMRs in the
      second network was reversible following weight loss. Our results suggest that CpG
      methylation in DMR networks is regulated concomitantly via aging and
      hyperglycemia and plays important roles in hepatic metabolic dysfunction,
      fibrosis, and potential tumorigenesis, which occur during the progression of
      NAFLD. By controlling weight and blood glucose levels, the methylation of DMRs in
      the second network may be reduced.

PMID- 30206279
TI  - Attraction effect of different colored cards on thrips Frankliniella intonsa in
      cowpea greenhouses in China.
AB  - The flower thrips Frankliniella intonsa (Trybom) is one of the most economically
      important pests in cowpea greenhouses in China. Widespread pesticide resistance
      of thrips and the negative environmental effects limit the application of
      pesticides for thrips control. Two commercial cowpea greenhouse experiments were
      designed to determine the color preference of F. intonsa to colored cards,
      including white, pink, pale green, light yellow, powder blue, crimson, yellow
      green, deep sky blue, dark slate blue, dark orange, medium orchid, gold, and
      black. Clear pieces of plastic were used as the control cards. Additionally, the
      effects of placement height and orientation (cardinal direction) of the cards
      were also studied. Both greenhouse trials showed that white cards were
      significantly more attractive to F. intonsa than the other 13 card colors,
      followed by deep sky blue cards. White or deep sky blue cards placed low to the
      ground were found to be most attractive to F. intonsa. Orientation of the colored
      cards also affected the attractiveness to F. intonsa. The results indicate that
      white sticky cards were significantly more attractive to F. intonsa than blue
      cards and therefore can be recommended to monitor F. intonsa population densities
      and to control them in cowpea greenhouses as part of integrated pest management
      programs.

PMID- 30206278
TI  - Trans-abdominal in vivo placental vessel occlusion using High Intensity Focused
      Ultrasound.
AB  - Pre-clinically, High Intensity Focused Ultrasound (HIFU) has been shown to safely
      and effectively occlude placental blood vessels in the acute setting, when
      applied through the uterus. However, further development of the technique to
      overcome the technical challenges of targeting and occluding blood vessels
      through intact skin remains essential to translation into human studies. So too
      does the assessment of fetal wellbeing following this procedure, and
      demonstration of the persistence of vascular occlusion. At 115 +/- 10 d
      gestational age (term~147 days) 12 pregnant sheep were exposed to HIFU (n = 6),
      or to a sham (n = 6) therapy through intact abdominal skin (1.66 MHz, 5 s
      duration, in situ ISPTA 1.3-4.4 kW.cm-2). Treatment success was defined as
      undetectable colour Doppler signal in the target placental vessel following HIFU
      exposures. Pregnancies were monitored for 21 days using diagnostic ultrasound
      from one day before HIFU exposure until term, when post-mortem examination was
      performed. Placental vessels were examined histologically for evidence of
      persistent vascular occlusion. HIFU occluded 31/34 (91%) of placental vessels
      targeted, with persistent vascular occlusion evident on histological examination
      20 days after treatment. The mean diameter of occluded vessels was 1.4 mm (range
      0.3-3.3 mm). All pregnancies survived until post mortem without evidence of
      significant maternal or fetal iatrogenic harm, preterm labour, maternal or fetal
      haemorrhage or infection. Three of six ewes exposed to HIFU experienced abdominal
      skin burns, which healed without intervention within 21 days. Mean fetal weight,
      fetal growth velocity and other measures of fetal biometry were not affected by
      exposure to HIFU. Fetal Doppler studies indicated a transient increase in the
      umbilical artery pulsatility index (PI) and a decrease in middle cerebral artery
      PI as a result of general anaesthesia, which was not different between sham and
      treatment groups. We report the first successful application of fully non
      invasive HIFU for occlusion of placental blood flow in a pregnant sheep model,
      with a low risk of significant complications. This proof of concept study
      demonstrates the potential of this technique for clinical translation.

PMID- 30206280
TI  - Seasonal consumption of polyphenol-rich fruits affects the hypothalamic leptin
      signaling system in a photoperiod-dependent mode.
AB  - Leptin has a central role in the maintenance of energy homeostasis, and its
      sensitivity is influenced by both the photoperiod and dietary polyphenols. The
      aim of this study was to investigate the effect of seasonal consumption of
      polyphenol-rich fruits on the hypothalamic leptin signaling system in non-obese
      and obese animals placed under different photoperiods. Non-obese and diet-induced
      obese male Fischer 344 rats were placed under either a short-day (SD) or long-day
      (LD) photoperiod and were supplemented with either 100 mg/kg of lyophilized red
      grapes or cherries. In non-obese animals, both fruits reduced energy balance
      independent of the photoperiod to which they were placed. However, the
      hypothalamic gene expression of Pomc was significantly up-regulated only in the
      SD photoperiod. In contrast, in obese animals only cherry significantly decreased
      the energy balance, although both fruits were able to counteract the diet-induced
      increase in hypothalamic AgRP mRNA levels when consumed during the SD
      photoperiod. In conclusion, the consumption of rich-polyphenol fruits may
      increase leptin sensitivity through the modulation of the hypothalamic leptin
      signal pathway mainly when consumed in the SD photoperiod. Therefore, fruit
      seasonality should be considered, as it can influence energy homeostasis and
      obesity.

PMID- 30206281
TI  - GmGRP-like gene confers Al tolerance in Arabidopsis.
AB  - Aluminium (Al) toxicity restrains water and nutrient uptake and is toxic to plant
      roots, ultimately inhibiting crop production. Here, we isolated and characterized
      a soybean glycine-rich protein-like gene (GmGRPL) that is mainly expressed in the
      root and that is regulated by Al treatment. Overexpression of GmGRPL can
      alleviate Al-induced root growth inhibition in Arabidopsis. The levels of IAA and
      ethylene in GmGRPL-overexpressing hairy roots were lower than those in control
      and RNA interference-exposed GmGRPL hairy roots with or without Al stress, which
      were mainly regulated by TAA1 and ACO, respectively. In transgenic soybean hairy
      roots, the MDA, H2O2 and O2-.content in GmGRPL-overexpressing hairy roots were
      less than that in control and RNA interference-exposed GmGRPL hairy roots under
      Al stress. In addition, IAA and ACC can enhance the expression level of the
      GmGRPL promoter with or without Al stress. These results indicated that GmGRPL
      can alleviate Al-induced root growth inhibition by regulating the level of IAA
      and ethylene and improving antioxidant activity.

PMID- 30206282
TI  - Bacillus velezensis A2 fermentation exerts a protective effect on renal injury
      induced by Zearalenone in mice.
AB  - Zearalenone (ZEN) is an estrogen-like mycotoxin occurring in food and feeds, and
      it can cause oxidative damage and apoptosis in the testis, liver, and kidney. A
      current concern for researchers is how to reduce the harm it causes to humans and
      animals. In this study, our aim was to isolate and identify a novel and efficient
      ZEN-detoxifying strain of bacteria, and we aimed to assess the protective effect
      of the isolated strain on kidney damage caused by ZEN in mice. Our results
      indicated that a strain of Bacillus velezensis (B. velezensis), named A2, could
      completely degrade ZEN (7.45 MUg/mL) after three days of incubation at 37 
      degrees C in the Luria-Bertani (LB) medium. This fermentation broth of the B.
      velezensis A2 strain was given to mice. The histopathological analysis indicated
      that the fermentation broth from the B. velezensis A2 strain reduced the degree
      of renal injury that is induced by ZEN. Furthermore, it greatly reduced the
      increase in serum levels of creatinine (CRE), uric acid (UA), and urea nitrogen
      (BUN) caused by ZEN. In addition, B. velezensis A2 strain also significantly
      inhibited the increase of malonaldehyde (MDA) content, and reversed the decreases
      of total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px)
      activities caused by ZEN. Studies have shown that ZEN is involved in the
      regulation of mRNA and protein levels of genes involved in the ER stress-induced
      apoptotic pathway, such as heavy chain binding protein (BIP), C-/-EBP homologous
      protein (CHOP), cysteine Aspartate-specific protease-12 (Caspase-12), c-Jun N
      terminal kinase (JNK), and BCL2-related X protein (Bcl-2 and Bax). However, when
      mice were administered the fermentation broth of the B. velezensis A2 strain, it
      significantly reversed the expressions of these genes in their kidney tissue. In
      conclusion, our results indicate that the newly identified strain of B.
      velezensis A2, has a protective effect from renal injury induced by ZEN in mice.
      This strain has a potential application in the detoxification of ZEN in feed and
      protects animals from ZEN poisoning.

PMID- 30206283
TI  - Unimpaired Neuropsychological Performance and Enhanced Memory Recall in Patients
      with Sbma: A Large Sample Comparative Study.
AB  - Peculiar cognitive profile of patients with SBMA has been described by fragmented
      literature. Our retrospective study reports the neuropsychological evaluations of
      a large cohort of patients in order to contribute towards the understanding of
      this field. We consider 64 neuropsychological evaluations assessing mnesic,
      linguistic and executive functions collected from 2013 to 2015 in patients
      attending at Motor Neuron Disease Centre of University of Padova. The battery
      consisted in: Digit Span forwards and backwards, Prose Memory test, Phonemic
      Verbal fluency and Trail making tests. ANCOVA statistics were employed to compare
      tests scores results with those obtained from a sample of healthy control
      subjects. Multiple linear regressions were used to study the effect on cognitive
      performance of CAG-repeat expansion, the degree of androgen insensitivity and
      their interaction to cognitive performance. Statistical analyses did not reveal
      altered scores in any neuropsychological tests among those adopted.
      Interestingly, patients performed significantly better in the Prose Memory test's
      score. No relevant associations were found with genetic, hormonal or clinical
      patients' profile. Results inconsistent with previous studies have been
      interpreted according to the phenomenon of somatic mosaicism. We suggest a
      testosterone-related and the mood state-dependant perspectives as two possible
      interpretations of the enhanced performances in the Prose Memory test. Further
      studies employing more datailed tests batteries are encouraged.

PMID- 30206285
TI  - Subtropical adaptation of a temperate plant (Brassica oleracea var. italica)
      utilizes non-vernalization-responsive QTLs.
AB  - While many tropical plants have been adapted to temperate cultivation, few
      temperate plants have been adapted to the tropics. Originating in Western Europe,
      Brassica oleracea vernalization requires a period of low temperature and BoFLC2
      regulates the transition to floral development. In B. oleracea germplasm selected
      in Taiwan, a non-vernalization pathway involving BoFLC3 rather than BoFLC2
      regulates curd induction. In 112 subtropical breeding lines, specific haplotype
      combinations of BoFLC3 and PAN (involved in floral organ identity and a
      positional candidate for additional curd induction variation) adapt B. oleracea
      to high ambient temperature and short daylength. Duplicated genes permitted
      evolution of alternative pathways for control of flowering in temperate and
      tropical environments, a principle that might be utilized via natural or
      engineered approaches in other plants. New insight into regulation of Brassica
      flowering exemplifies translational agriculture, tapping knowledge of botanical
      models to improve food security under projected climate change scenarios.

PMID- 30206284
TI  - Metabolic profiling and targeted lipidomics reveals a disturbed lipid profile in
      mothers and fetuses with intrauterine growth restriction.
AB  - Fetal growth may be impaired by poor placental function or maternal conditions,
      each of which can influence the transfer of nutrients and oxygen from the mother
      to the developing fetus. Large-scale studies of metabolites (metabolomics) are
      key to understand cellular metabolism and pathophysiology of human conditions.
      Herein, maternal and cord blood plasma samples were used for NMR-based metabolic
      fingerprinting and profiling, including analysis of the enrichment of circulating
      lipid classes and subclasses, as well as the number of sub-fraction particles and
      their size. Changes in phosphatidylcholines and glycoproteins were prominent in
      growth-restricted fetuses indicating significant alterations in their abundance
      and biophysical properties. Lipoprotein profiles showed significantly lower
      plasma concentrations of cholesterol-intermediate density lipoprotein (IDL),
      triglycerides-IDL and high-density lipoprotein (HDL) in mothers of growth
      restricted fetuses compared to controls (p < 0.05). In contrast, growth
      restricted fetuses had significantly higher plasma concentrations of cholesterol
      and triglycerides transporting lipoproteins [LDL, IDL, and VLDL, (p < 0.005;
      all)], as well as increased VLDL particle types (large, medium and small).
      Significant changes in plasma concentrations of formate, histidine, isoleucine
      and citrate in growth-restricted fetuses were also observed. Comprehensive
      metabolic profiling reveals that both, mother and fetuses of pregnancies
      complicated with fetal growth restriction have a substantial disruption in lipid
      metabolism.

PMID- 30206287
TI  - Naphthol Blue Black and 99mTc-Labeled Mannosylated Human Serum Albumin (99mTc
      MSA) Conjugate as a Multimodal Lymph Node Mapping Nanocarrier.
AB  - 99mTc-labeled mannosylated human serum albumin (MSA) has been reported as a
      sentinel lymph node (SLN)-imaging agent by binding to macrophages in the LNs. By
      conjugating it with blue dye, we developed a new multimodal radio-nanocarrier by
      visual investigation, fluorescence imaging, and single photon emission computed
      tomography (SPECT)/computed tomography (CT). Binding affinities of seven blue
      dyes to MSA were tested. According to the spectroscopic study and visual
      inspection of MSA-bound dyes, naphthol blue black (NBB) was selected as the best
      candidate of multimodal agent. Thus, 99mTc-MSA-NBB conjugate was prepared and
      further investigated using mice. After footpad injection, it showed high
      popliteal LN accumulation at 1 h. SPECT/CT also showed high popliteal as well as
      inguinal LN uptakes at 10 min that sustained until 2 h. In conclusion, we
      prepared a multimodal SLN imaging radio-nanocarrier, 99mTc-MSA-NBB conjugate, and
      confirmed its excellency as a multimodal probe for SLN mapping.

PMID- 30206286
TI  - Reconfiguration of the plastid genome in Lamprocapnos spectabilis: IR boundary
      shifting, inversion, and intraspecific variation.
AB  - We generated a complete plastid genome (plastome) sequence for Lamprocapnos
      spectabilis, providing the first complete plastome from the subfamily
      Fumarioideae (Papaveraceae). The Lamprocapnos plastome shows large differences in
      size, structure, gene content, and substitution rates compared with two sequenced
      Papaveraceae plastomes. We propose a model that explains the major rearrangements
      observed, involving at least six inverted repeat (IR) boundary shifts and five
      inversions, generating a number of gene duplications and relocations, as well as
      a two-fold expansion of the IR and miniaturized small single-copy region. A
      reduction in the substitution rates for genes transferred from the single-copy
      regions to the IR was observed. Accelerated substitution rates of plastid accD
      and clpP were detected in the Lamprocapnos plastome. The accelerated substitution
      rate for the accD gene was correlated with a large insertion of amino acid repeat
      (AAR) motifs in the middle region, but the forces driving the higher substitution
      rate of the clpP gene are unclear. We found a variable number of AARs in
      Lamprocapnos accD and ycf1 genes within individuals, and the repeats were
      associated with coiled-coil regions. In addition, comparative analysis of three
      Papaveraceae plastomes revealed loss of rps15 in Papaver, and functional
      replacement to the nucleus was identified.

PMID- 30206288
TI  - Investigation of hindbrain activity during active locomotion reveals inhibitory
      neurons involved in sensorimotor processing.
AB  - Locomotion in vertebrates relies on motor circuits in the spinal cord receiving
      inputs from the hindbrain to execute motor commands while dynamically integrating
      proprioceptive sensory feedback. The spatial organization of the neuronal
      networks driving locomotion in the hindbrain and role of inhibition has not been
      extensively investigated. Here, we mapped neuronal activity with single-cell
      resolution in the hindbrain of restrained transgenic Tg(HuC:GCaMP5G) zebrafish
      larvae swimming in response to whole-field visual motion. We combined large-scale
      population calcium imaging in the hindbrain with simultaneous high-speed
      recording of the moving tail in animals where specific markers label glycinergic
      inhibitory neurons. We identified cells whose activity preferentially correlates
      with the visual stimulus or motor activity and used brain registration to compare
      data across individual larvae. We then morphed calcium imaging data onto the
      zebrafish brain atlas to compare with known transgenic markers. We report cells
      localized in the cerebellum whose activity is shut off by the onset of the visual
      stimulus, suggesting these cells may be constitutively active and silenced during
      sensorimotor processing. Finally, we discover that the activity of a medial
      stripe of glycinergic neurons in the domain of expression of the transcription
      factor engrailed1b is highly correlated with the onset of locomotion. Our efforts
      provide a high-resolution, open-access dataset for the community by comparing our
      functional map of the hindbrain to existing open-access atlases and enabling
      further investigation of this population's role in locomotion.

PMID- 30206289
TI  - Validation of beat by beat fetal heart signals acquired from four-channel fetal
      phonocardiogram with fetal electrocardiogram in healthy late pregnancy.
AB  - Fetal heart rate monitoring is an essential obstetric procedure, however, false
      positive results cause unnecessary obstetric interventions and healthcare cost.
      In this study, we propose a low cost and non-invasive fetal phonocardiography
      based signal system to measure the fetal heart sounds and fetal heart rate.
      Phonocardiogram (PCG) signals contain acoustic information reflecting the
      contraction and relaxation of the heart. We have developed a four-channel
      recording device with four separated piezoelectric sensors harnessed by a cloth
      sheet to record abdominal phonogram signals. A multi-lag covariance matrix based
      eigenvalue decomposition technique was used to extract fetal and maternal heart
      sounds as well as maternal breathing movement. In order to validate the fetal
      heart sounds extracted by PCG signal processing, 10 minutes' simultaneous
      recordings of fetal Electrocardiogram (fECG) and abdominal phonogram from 15
      pregnant women (27 +/- 5-year-old) with fetal gestation ages between 33 and 40
      weeks were obtained and processed. Highly significant (p < 0.01) correlation (r =
      0.96; N = 270) was found between beat to beat fetal heart rate (FHRECG) from fECG
      and the same (FHRPCG) from fetal PCG signals. Bland-Altman plot of FHRECG and
      FHRPCG shows good agreement (<5% difference). We conclude that the proposed beat
      to beat fetal heart rate measurement system would be useful for monitoring fetal
      neurological wellbeing as a better alternative to traditional cardiotocogram
      based antenatal fetal heart rate monitoring.

PMID- 30206290
TI  - Author Correction: Whole exome sequencing reveals rare variants linked to
      congenital pouch colon.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 30206291
TI  - Clinical and genetic backgrounds of hypertrophic cardiomyopathy with mid
      ventricular obstruction.
AB  - Hypertrophic cardiomyopathy (HCM) is characterized by unexplained left
      ventricular hypertrophy. This study aimed to reveal the clinical and genetic
      backgrounds of the unique HCM with mid-ventricular obstruction (HCM-MVO) subtype.
      We identified 34 patients with HCM-MVO in our cohort, and about half (47%) of
      these patients experienced adverse events. We analyzed 67 cardiomyopathy
      associated genes in the patients. In total, 44% of patients with HCM-MVO carried
      the cardiomyopathy-associated genetic variant (CAGV) in 14 genes. Only 21% of
      patients carried HCM-associated CAGVs in major sarcomere-encoding genes, while
      18% of patients carried CAGVs in dilated cardiomyopathy/arrhythmogenic right
      ventricular cardiomyopathy-associated genes. CAGVs were more frequent in patients
      with asymmetric septal hypertrophy (ASH) than in those without ASH. These
      findings suggest that HCM-MVO is a high-risk group and may have different
      etiologies from typical HCM.

PMID- 30206292
TI  - Characterization of nitrogen deposition in a megalopolis by means of atmospheric
      biomonitors.
AB  - An increase of nitrogen deposition resulting from human activities is not only a
      major threat for global biodiversity, but also for human health, especially in
      highly populated regions. It is thus important and in some instances legally
      mandated to monitor reactive nitrogen species in the atmosphere. The utilization
      of widely distributed biological species suitable for biomonitoring may be a good
      alternative. We assessed the suitability of an ensemble of atmospheric
      biomonitors of nitrogen deposition by means of an extensive sampling of a lichen,
      two mosses, and a bromeliad throughout the Valley of Mexico, whose population
      reaches 30 million, and subsequent measurements of nitrogen metabolism
      parameters. In all cases we found significant responses of nitrogen content, C:N
      ratio and the delta15N to season and site. In turn, the delta15N for the mosses
      responded linearly to the wet deposition. Also, the nitrogen content (R2 = 0.7),
      the C:N ratio (R2 = 0.6), and delta15N (R2 = 0.5) for the bromeliad had a linear
      response to NOx. However, the bromeliad was not found in sites with NOx
      concentrations exceeding 80 ppb, apparently of as a consequence of excess
      nitrogen. These biomonitors can be utilized in tandem to determine the status of
      atmospheric nitrogenous pollution in regions without monitoring networks for
      avoiding health problems for ecosystems and humans.

PMID- 30206293
TI  - Serum IgG2 levels are specifically associated with whole-body insulin-mediated
      glucose disposal in non-diabetic offspring of type 2 diabetic individuals: a
      cross-sectional study.
AB  - Preclinical studies suggested that IgG2c isotype may specifically impair skeletal
      muscle insulin sensitivity in mice. In this study we investigated the association
      between serum levels of the four IgG subclasses and insulin sensitivity in non
      diabetic individuals. Total IgG, IgG1, IgG2, IgG3 and IgG4 levels were measured
      in 262 subjects. Whole-body insulin sensitivity was assessed by euglycemic
      hyperinsulinemic clamp. IgG2 levels were positively correlated with BMI, waist
      circumference, 2-h post-load glucose levels and complement C3. Serum IgG2, but
      not IgG1, IgG3 and IgG4 levels were negatively correlated with whole-body insulin
      sensitivity (r = -0.17; P = 0.003) and muscle insulin sensitivity index (r = 
      0.16; P = 0.03) after adjustment for age and gender. No significant correlation
      was found between IgG2 levels and hepatic insulin resistance assessed by HOMA-IR
      and liver IR index. In a multivariable regression analysis including variables
      known to affect insulin sensitivity such as age, gender, BMI, smoking, lipids,
      inflammatory markers, fasting and 2-h post-load glucose levels, IgG2 levels were
      independently associated with insulin-stimulated glucose disposal (beta = -0.115,
      95% CI: -0.541 to -0.024; P = 0.03). These data demonstrate the independent
      association between higher levels of IgG2 and decreased whole-body insulin
      sensitivity, thus confirming in humans the animal-based evidence indicating the
      pathogenic role of IgG2 in insulin resistance.

PMID- 30206294
TI  - Zinc uptake promotes myoblast differentiation via Zip7 transporter and activation
      of Akt signalling transduction pathway.
AB  - Myogenic regeneration occurs through a chain of events beginning with the output
      of satellite cells from quiescent state, formation of competent myoblasts and
      later fusion and differentiation into myofibres. Traditionally, growth factors
      are used to stimulate muscle regeneration but this involves serious off-target
      effects, including alterations in cell homeostasis and cancer. In this work, we
      have studied the use of zinc to trigger myogenic differentiation. We show that
      zinc promotes myoblast proliferation, differentiation and maturation of
      myofibres. We demonstrate that this process occurs through the PI3K/Akt pathway,
      via zinc stimulation of transporter Zip7. Depletion of zinc transporter Zip7 by
      RNA interference shows reduction of both PI3K/Akt signalling and a significant
      reduction of multinucleated myofibres and myotubes development. Moreover, we show
      that mature myofibres, obtained through stimulation with high concentrations of
      zinc, accumulate zinc and so we hypothesise their function as zinc reservoirs
      into the cell.

PMID- 30206295
TI  - A carbon nanotube integrated microfluidic device for blood plasma extraction.
AB  - Blood is a complex fluid consisting of cells and plasma. Plasma contains key
      biomarkers essential for disease diagnosis and therapeutic monitoring. Thus, by
      separating plasma from the blood, it is possible to analyze these biomarkers.
      Conventional methods for plasma extraction involve bulky equipment, and
      miniaturization constitutes a key step to develop portable devices for plasma
      extraction. Here, we integrated nanomaterial synthesis with microfabrication, and
      built a microfluidic device. In particular, we designed a double-spiral channel
      able to perform cross-flow filtration. This channel was constructed by growing
      aligned carbon nanotubes (CNTs) with average inter-tubular distances of ~80 nm,
      which resulted in porosity values of ~93%. During blood extraction, these aligned
      CNTs allow smaller molecules (e.g., proteins) to pass through the channel wall,
      while larger molecules (e.g., cells) get blocked. Our results show that our
      device effectively separates plasma from blood, by trapping blood cells. We
      successfully recovered albumin -the most abundant protein inside plasma- with an
      efficiency of ~80%. This work constitutes the first report on integrating
      biocompatible nitrogen-doped CNT (CNxCNT) arrays to extract plasma from human
      blood, thus widening the bio-applications of CNTs.

PMID- 30206296
TI  - Matched Short-Term Depression and Recovery Encodes Interspike Interval at a
      Central Synapse.
AB  - Reversible decreases in synaptic strength, known as short-term depression (STD),
      are widespread in neural circuits. Various computational roles have been
      attributed to STD but these tend to focus upon the initial depression rather than
      the subsequent recovery. We studied the role of STD and recovery at an excitatory
      synapse between the fast extensor tibiae (FETi) and flexor tibiae (flexor) motor
      neurons in the desert locust (Schistocerca gregaria) by making paired
      intracellular recordings in vivo. Over behaviorally relevant pre-synaptic spike
      frequencies, we found that this synapse undergoes matched frequency-dependent STD
      and recovery; higher frequency spikes that evoke stronger, faster STD also
      produce stronger, faster recovery. The precise matching of depression and
      recovery time constants at this synapse ensures that flexor excitatory post
      synaptic potential (EPSP) amplitude encodes the presynaptic FETi interspike
      interval (ISI). Computational modelling shows that this precise matching enables
      the FETi-flexor synapse to linearly encode the ISI in the EPSP amplitude, a
      coding strategy that may be widespread in neural circuits.

PMID- 30206297
TI  - Hydroxyurea in the management of sickle cell disease: pharmacogenomics and
      enzymatic metabolism.
AB  - Hydroxyurea (HU) was approved to be used in the treatment of sickle cell disease
      (SCD) because of its anti-sickling potential. However, there is variability in HU
      response among SCD patients and this can be due to physiological, socioeconomic,
      environmental, metabolic and/or genetic factors. The present review focuses on
      the latter two. Three quantitative trait loci, HBG2, BCL11A and HMIP, have been
      suggested as important markers for HU response. Other genes (ASS1, KLF10, HAO2,
      MAP3K5, PDE7B, TOX, NOS1, NOS2A, FLT1, ARG1, ARG2, UGT1A1, OR51B5/6, SIN3A,
      SALL2, SAR1A, UTB, OCTN1, CYP2C9, AQP9, MPO, CYP2E1, and GSTT1) have also been
      considered. Studies implicate catalase, urease, horseradish peroxidase and
      enzymes of CYP450 family in HU metabolism. However, little is known about these
      enzymes. Therefore, further studies are needed to elucidate the metabolic pathway
      of HU, which will facilitate pharmacogenomic studies and help in identification
      of candidate genes for predicting HU response.

PMID- 30206299
TI  - An optimized prediction framework to assess the functional impact of
      pharmacogenetic variants.
AB  - Prediction of phenotypic consequences of mutations constitutes an important
      aspect of precision medicine. Current computational tools mostly rely on
      evolutionary conservation and have been calibrated on variants associated with
      disease, which poses conceptual problems for assessment of variants in poorly
      conserved pharmacogenes. Here, we evaluated the performance of 18 current
      functionality prediction methods leveraging experimental high-quality activity
      data from 337 variants in genes involved in drug metabolism and transport and
      found that these models only achieved probabilities of 0.1-50.6% to make informed
      conclusions. We therefore developed a functionality prediction framework
      optimized for pharmacogenetic assessments that significantly outperformed current
      algorithms. Our model achieved 93% for both sensitivity and specificity for both
      loss-of-function and functionally neutral variants, and we confirmed its superior
      performance using cross validation analyses. This novel model holds promise to
      improve the translation of personal genetic information into biological
      conclusions and pharmacogenetic recommendations, thereby facilitating the
      implementation of Next-Generation Sequencing data into clinical diagnostics.

PMID- 30206298
TI  - A genome-wide association and admixture mapping study of bronchodilator drug
      response in African Americans with asthma.
AB  - Short-acting beta2-adrenergic receptor agonists (SABAs) are the most commonly
      prescribed asthma medications worldwide. Response to SABAs is measured as
      bronchodilator drug response (BDR), which varies among racial/ethnic groups in
      the United States. However, the genetic variation that contributes to BDR is
      largely undefined in African Americans with asthma. To identify genetic variants
      that may contribute to differences in BDR in African Americans with asthma, we
      performed a genome-wide association study (GWAS) of BDR in 949 African-American
      children with asthma, genotyped with the Axiom World Array 4 (Affymetrix, Santa
      Clara, CA) followed by imputation using 1000 Genomes phase III genotypes. We used
      linear regression models adjusting for age, sex, body mass index (BMI) and
      genetic ancestry to test for an association between BDR and genotype at single
      nucleotide polymorphisms (SNPs). To increase power and distinguish between shared
      vs. population-specific associations with BDR in children with asthma, we
      performed a meta-analysis across 949 African Americans and 1830 Latinos (total =
      2779). Finally, we performed genome-wide admixture mapping to identify regions
      whereby local African or European ancestry is associated with BDR in African
      Americans. We identified a population-specific association with an intergenic SNP
      on chromosome 9q21 that was significantly associated with BDR (rs73650726, p =
      7.69 * 10-9). A trans-ethnic meta-analysis across African Americans and Latinos
      identified three additional SNPs within the intron of PRKG1 that were
      significantly associated with BDR (rs7903366, rs7070958 and rs7081864, p <= 5 *
      10-8). Our results failed to replicate in three additional populations of 416
      Latinos and 1615 African Americans. Our findings indicate that both population
      specific and shared genetic variation contributes to differences in BDR in
      minority children with asthma, and that the genetic underpinnings of BDR may
      differ between racial/ethnic groups.

PMID- 30206300
TI  - Concordance between glucose-6-phosphate dehydrogenase (G6PD) genotype and
      phenotype and rasburicase use in patients with hematologic malignancies.
AB  - Phenotypic rather than genotypic tests remain the gold standard for diagnosing
      glucose-6-phosphate dehydrogenase (G6PD) deficiency. However, with increasing use
      of genomic arrays and whole exome or genome sequencing, G6PD genetic data are
      increasingly available. We examined the utility of G6PD genetic data in patients
      with hematologic malignancies and the association of G6PD genotype and phenotype
      with rasburicase-induced methemoglobinemia. We analyzed G6PD activity for 990
      patients. Genotype data were available from the Affymetrix DMET array (n = 379),
      whole exome sequencing (n = 374), and/or the Illumina exome array (n = 634) for
      645 patients. Medical records of 341 patients with methemoglobin measures were
      assessed for the administration of rasburicase. We observed 5 non-synonymous
      SNPs, 4 of which were known to be associated with deficient G6PD activity (WHO
      Class I-III). Genotyping 367 males resulted in a positive predictive value of
      81.8% (47.8-96.8%), and two males with a Class I-III allele having normal
      activity both received a red blood cell transfusion prior to the activity assay.
      However, genotyping males had only 39.1% (20.5-61.2%) sensitivity. Two of the 12
      heterozygous females had deficient G6PD activity. Rasburicase-induced
      methemoglobinemia occurred in 6 patients, 5 of whom had at least one Class I-III
      allele, despite 2 of these having normal G6PD activity. We conclude that although
      an apparent nondeficient genotype does not necessarily imply a normal phenotype,
      a deficient genotype result indicates a deficient phenotype in those without
      transfusions, and may be a useful adjuct to phenotype to prevent adverse drug
      reactions.

PMID- 30206301
TI  - Inferring the phase response curve from observation of a continuously perturbed
      oscillator.
AB  - Phase response curves are important for analysis and modeling of oscillatory
      dynamics in various applications, particularly in neuroscience. Standard
      experimental technique for determining them requires isolation of the system and
      application of a specifically designed input. However, isolation is not always
      feasible and we are compelled to observe the system in its natural environment
      under free-running conditions. To that end we propose an approach relying only on
      passive observations of the system and its input. We illustrate it with
      simulation results of an oscillator driven by a stochastic force.

PMID- 30206303
TI  - Progress in adjuvant systemic therapy for breast cancer.
AB  - The prognosis of patients with early stage breast cancer has greatly improved in
      the past three decades. Following the first adjuvant endocrine therapy and
      chemotherapy trials, continuous improvements of clinical outcomes have been
      achieved through intense therapeutic escalation, albeit with increased health
      care costs and treatment-related toxicities. In contrast to the advances achieved
      in surgery or radiotherapy, the identification of the patient subgroups that will
      derive clinical benefit from therapeutic escalation has proved to be a daunting
      process hindered by a lack of collaboration between scientific groups and by the
      pace of drug development. In the past few decades, initiatives towards de
      escalation of systemic adjuvant treatment have achieved success. Herein, we
      summarize attempts to escalate and de-escalate adjuvant systemic treatment for
      patients with breast cancer and argue that new, creative trial designs focused on
      patients' actual needs rather than on maximizing drug market size are needed.
      Ultimately, the adoption of effective treatments that do not needlessly expose
      patients and health-care systems to harm demands extensive international
      collaboration between academic groups, governments, and pharmaceutical companies.

PMID- 30206302
TI  - Particular CSF sphingolipid patterns identify iNPH and AD patients.
AB  - Idiopathic normal pressure hydrocephalus (iNPH) is characterized by reversible
      neurological symptoms due to an impairment in cerebrospinal fluid (CSF)
      clearance. In these patients, cognitive functions are severely impaired, with a
      scenario similar to Alzheimer's disease (AD), making the differential diagnosis
      difficult and highlighting the need of new markers. We analyzed the composition
      of sphingolipids (SLs) in serum, by combining a single phase extraction with a
      high-performance thin-layer chromatography (HPTLC) primuline-profiling, and, in
      CSF, by MALDI profiling and LC-MS. Ceramides and sphingomyelins (SMs) were
      similar in serum of iNPH and AD patients compared to healthy controls, whereas,
      in CSF, MALDI profiling indicated that: 1) SM C24:1 is significantly decreased in
      AD compared to iNPH patients and controls (Kruskal-Wallis p-value < 0.00001); 2)
      phosphatidylcholine (PC) 36:2 is increased in iNPH patients (p-value < 0.001). LC
      MS identified an increasing trend of Cer C24:0 and of a set of SMs in patients
      with AD, a significant decrease of sphingosine-1-phosphate (S1P) (t-test p-value
      0.0325) and an increase of glucosylceramide (GlcCer) C24:0 (p-value 0.0037) in AD
      compared to iNPH patients. In conclusion CSF PC 36:2, SM C24:1, S1P, and GlcCer
      can contribute to improve the differential diagnosis of patients with iNPH or AD
      and foster preventive therapeutic strategies in the early phase of the disease.

PMID- 30206305
TI  - Identifying the early 2000s hiatus associated with internal climate variability.
AB  - This study focuses on re-examining the early 2000s hiatus and the associated key
      components of the global mean surface temperature (GMST) using multiscale
      statistics for five well-known gridded surface temperature and two reanalysis
      datasets. The hiatus is characterized as a near-zero trend on the decadal scale
      corresponding to the maximum P-value via an F-test in statistics. The results
      reveal that the hiatus exists in both the GMST and global mean air temperature
      (GMAT) time series, rather than in global warming component, which has maintained
      an approximately constant rate of change of approximately 0.08  degrees C/decade
      over the past three decades. The hiatus's duration is different from that of time
      series such as 2002-2012/2001-2013/2002-2014 in HadCRUT4, NOAA-old, ERA-Interim
      and NCEP-R2. The newly gridded datasets with data infilling or bias correction
      for interpreting the sea surface temperature (SST) measurement from the old
      versions show a slightly higher trend from 2002-2012 than the hiatus, which is
      thus regarded as a slowdown. Comparison suggests that the hiatus should be during
      the period 2002-2012. Orthogonal wavelet decomposition of the temperature time
      series shows that the hiatus was merely a decadal balance between cooling from
      interannual variability and global warming, in addition to weak warming from
      interdecadal and multidecadal climate oscillations. In addition, the evolutions
      of the GMST's interannual composites are well coincided with Nino3.4 SST
      anomalies, which is consistent with the numerical simulation performed by Kosaka
      and Xie in 2013. Hence, it is the anomalous El Nino Southern Oscillation (ENSO)
      events in the early 2000s that caused the hiatus despite a constant rate of
      global warming and the maximum magnitude of the multidecadal composite that led
      to the limited contribution to the trend during this period. The multidecadal
      composite follows a downward path, which implies that future climate conditions
      will likely rely on competition between multidecadal cooling and global warming
      if the multidecadal climate cycle repeats, as was experienced during the second
      half of the twentieth century.

PMID- 30206306
TI  - COVA4231, a potent CD3/CD33 bispecific FynomAb with IgG-like pharmacokinetics for
      the treatment of acute myeloid leukemia.

PMID- 30206304
TI  - Transcriptomic analyses of cacao cell suspensions in light and dark provide
      target genes for controlled flavonoid production.
AB  - Catechins, including catechin (C) and epicatechin (E), are the main type of
      flavonoids in cacao seeds. They play important roles in plant defense and have
      been associated with human health benefits. Although flavonoid biosynthesis has
      been extensively studied using in vitro and in vivo models, the regulatory
      mechanisms controlling their accumulation under light/dark conditions remain
      poorly understood. To identify differences in flavonoid biosynthesis
      (particularly catechins) under different light treatments, we used cacao cell
      suspensions exposed to white-blue light and darkness during 14 days. RNA-Seq was
      applied to evaluate differential gene expression. Our results indicate that light
      can effectively regulate flavonoid profiles, inducing a faster accumulation of
      phenolic compounds and shifting E/C ratios, in particular as a response to
      switching from white to blue light. The results demonstrated that HY5, MYB12, ANR
      and LAR were differentially regulated under light/dark conditions and could be
      targeted by overexpression aiming to improve catechin synthesis in cell cultures.
      In conclusion, our RNA-Seq analysis of cacao cells cultured under different light
      conditions provides a platform to dissect key aspects into the genetic regulatory
      network of flavonoids. These light-responsive candidate genes can be used further
      to modulate the flavonoid production in in vitro systems with value-added
      characteristics.

PMID- 30206307
TI  - Transmissible ER stress reconfigures the AML bone marrow compartment.
AB  - Successive adaptation of the bone marrow (BM) from homeostatic hematopoietic
      microenvironment to a self-reinforcing niche is an integral aspect of
      leukemogenesis. Yet, the cellular mechanisms underlying these functional
      alterations remain to be defined. Here, we found that AML incursion precipitates
      compartmental endoplasmic reticulum (ER) stress and an unfolded protein response
      (UPR) in both leukemia and stromal cells. We observed that extracellular vesicles
      (EV) transmit ER stress in vivo from the AML xenograft to BM stroma, whereby the
      upregulation of core UPR components drives subsequent osteolineage
      differentiation of mesenchymal stem cells (MSC). Finally, we show that the
      underlying mechanism involves quantitative incorporation and cell-cell transfer
      of Bone Morphogenic Protein 2 (BMP2), a potent osteogenic signal, by AML-EVs.
      Corroborative studies in AML patient samples support the translational relevance
      of AML-EVs as a platform for BMP trafficking and source of compartmental
      crosstalk. Transmissible ER stress was previously identified as a source of
      chemoresistance in solid tumor models, and this work reveals a role in remodeling
      the BM niche in AML.

PMID- 30206309
TI  - Enediyne-activated, EGFR-targeted human beta-defensin 1 has therapeutic efficacy
      against non-small cell lung carcinoma.
AB  - Human beta-defensins contain an oncolytic motif that binds to tumor cell
      membranes and mediate permeabilization, rapid induction of cytolysis, and
      apoptosis. Previous studies have indicated that a fragment of the mature human
      beta-defensin-1 (HBD1) peptide (DF) has antitumor properties. While targeted drug
      treatments using fusion proteins have been shown to increase drug efficacy, this
      phenomenon has not been studied for this defensin. Thus, in this study, we
      designed and prepared a fusion protein containing this HBD1 fragment and an
      epidermal growth factor receptor (EGFR)-targeting oligopeptide (Ec) as well as
      lidamycin (LDM), an extremely potent cytotoxic antitumor antibiotic, which
      consists of an apoprotein (LDP) and a highly active enediyne (AE). The fusion
      protein (Ec-LDP-DF) and its enediyne-integrated fusion protein (Ec-LDP(AE)-DF)
      were then purified and used to treat lung carcinoma cells in culture as well as
      lung carcinoma xenograft mouse models. The multifunctional fusion protein Ec-LDP
      DF was shown to effectively bind to EGFR-expressing tumor cells. Furthermore, the
      enediyne-energized Ec-LDP(AE)-DF analog exhibited extremely potent cytotoxicity
      in NSCLC cell lines and an IC50 less than 10-10 mol/L. Ec-LDP(AE)-DF also
      significantly inhibited the growth of human carcinoma A549 and H460 xenografts in
      athymic mice at well-tolerated doses. Treatment resulted in cell cycle arrest and
      apoptosis in a dose-dependent manner. EGF-stimulated EGFR phosphorylation was
      also abolished by Ec-LDP(AE)-DF. In summary, our understanding of the role of
      defensins in cancer development and progression is continually expanding, and Ec
      LDP(AE)-DF is a promising cancer cell-targeting agent for NSCLC.

PMID- 30206308
TI  - Downregulating Notch counteracts KrasG12D-induced ERK activation and oxidative
      phosphorylation in myeloproliferative neoplasm.
AB  - The Notch signaling pathway contributes to the pathogenesis of a wide spectrum of
      human cancers, including hematopoietic malignancies. Its functions are highly
      dependent on the specific cellular context. Gain-of-function NOTCH1 mutations are
      prevalent in human T-cell leukemia, while loss of Notch signaling is reported in
      myeloid leukemias. Here, we report a novel oncogenic function of Notch signaling
      in oncogenic Kras-induced myeloproliferative neoplasm (MPN). We find that
      downregulation of Notch signaling in hematopoietic cells via DNMAML expression or
      Pofut1 deletion significantly blocks MPN development in KrasG12D mice in a cell
      autonomous manner. Further mechanistic studies indicate that inhibition of Notch
      signaling upregulates Dusp1, a dual phosphatase that inactivates p-ERK, and
      downregulates cytokine-evoked ERK activation in KrasG12D cells. Moreover,
      mitochondrial metabolism is greatly enhanced in KrasG12D cells but significantly
      reprogrammed by DNMAML close to that in control cells. Consequently, cell
      proliferation and expanded myeloid compartment in KrasG12D mice are significantly
      reduced. Consistent with these findings, combined inhibition of the MEK/ERK
      pathway and mitochondrial oxidative phosphorylation effectively inhibited the
      growth of human and mouse leukemia cells in vitro. Our study provides a strong
      rational to target both ERK signaling and aberrant metabolism in oncogenic Ras
      driven myeloid leukemia.

PMID- 30206310
TI  - Vitamin D protects human melanocytes against oxidative damage by activation of
      Wnt/beta-catenin signaling.
AB  - Vitamin D analogs have been widely utilized for the treatment of vitiligo, but
      the molecular mechanism underlying their pharmacological effects (especially
      their antioxidant properties) has not yet been investigated. We evaluated the
      relationship between serum vitamin D level and oxidative damage severity in
      vitiligo patients, and investigated the molecular mechanism of vitamin D in
      protecting melanocytes against oxidative stress. Serum levels of 25
      hydroxyvitamin D and malondialdehyde (MDA) were first measured in patients. A
      variety of in vitro experiments such as intracellular reactive oxygen species
      (ROS), cellular viability, migration, and apoptotic assays were then performed to
      detect the effects of vitamin D or beta-catenin silencing on H2O2-treated
      melanocytes. Expression of Wnt/beta-catenin, Nrf2, apoptotic, and MITF pathways
      was finally examined using quantitative real-time PCR and western blot. In this
      study, we initially found that vitamin D insufficiency was closely associated
      with the severity of oxidative stress in vitiligo patients. Using ex vivo cell
      models, we further showed that vitamin D positively modulated beta-catenin
      signaling at both translational and posttranslational levels in melanocytes under
      oxidative stress. Like WNT agonists, vitamin D significantly inhibited ROS
      accumulation and cell apoptosis in H2O2-treated melanocytes and promoted their
      proliferative and migratory activity, while the protective effects of vitamin D
      against oxidative stress were abolished by beta-catenin silencing in melanocytes.
      Furthermore, beta-catenin deficiency also blocked the activation of Nrf2 and MITF
      as well as the inhibition of apoptosis induced by vitamin D. Taken together,
      vitamin D insufficiency was associated with severity of oxidative stress in
      vitiligo patients. Our work also provides new insights into the mechanism of
      vitamin D against vitiligo, in which vitamin D protects melanocytes against
      oxidative stress by activating Wnt/beta-catenin signaling.

PMID- 30206311
TI  - Trends in the characteristics of human functional genomic data on the gene
      expression omnibus, 2001-2017.
AB  - The gene expression omnibus (GEO) is the world's largest public repository of
      functional genomic data. Despite its broad use in secondary genomic analyses, the
      temporal trends in the characteristics of genomic data on GEO, including
      experimental procedures, geographic origin, funder(s), and related disease, have
      not been examined. We identified 75,376 Series deposited to the GEO during 2001
      2017 and built a database of all human genomic data (39,076 Series, 51.8% of all
      Series). Using the associated publications, we obtained funding information and
      identified the related disease area. Of the Series with classified disease areas,
      the two most common were cancer (n = 12,688, 32.5%) and immunologic diseases (n =
      2,393, 6.1%), while the percentages of all other disease areas were below 5%,
      including neurological diseases (n = 1733, 4.4%), infectious diseases (n = 1225,
      3.1%), diabetes (n = 828, 2.1%), and cardiovascular diseases (n = 299, 0.8%). In
      recent years, there has been a significant increase in the use of high-throughput
      sequencing (HTS), protein array and multiple-platform technologies, as well as in
      the proportion of North American deposits. Compared to those from other regions,
      North American deposits appeared to lead the shift from array-based to HTS
      technologies (odds ratio [OR], 95% confidence intervals [CI] = 3.39, 3.23-3.55, P
      = 9.40E-323), and were less likely to focus on a major disease area (OR = 0.64,
      95% CI: 0.61-0.67, P = 5.02E-107), suggesting a greater emphasis on basic science
      in North America. Furthermore, the Series utilizing HTS were less likely to be
      disease-classified compared to other technologies (OR = 0.39, 95% CI: 0.37-0.41,
      P = 1.00E-322), suggesting a preferential use or adoption of HTS in basic science
      settings. Finally, funding from the NHGRI, NCI, NIEHS, and NCCR resulted in a
      higher number of GEO Series per grant than other NIH institutes, demonstrating
      different preferences on genomic studies among awardees of NIH institutes. Our
      findings demonstrate geographic, technological, and funding disparities in the
      trends of GEO deposit characteristics.

PMID- 30206312
TI  - The STAT3 inhibitor S3I-201 suppresses fibrogenesis and angiogenesis in liver
      fibrosis.
AB  - Liver fibrosis is a common pathological response to chronic hepatic injury. STAT3
      is actively involved in the fibrogenesis and angiogenesis seen in liver fibrosis.
      S3I-201 (NSC 74859) is a chemical inhibitor of STAT3 activity, which blocks the
      dimerization of STAT3, STAT3-DNA binding and transcription activity. This study
      evaluated the effects of S3I-201 against liver fibrosis. S3I-201 inhibited the
      proliferation, migration, and actin filament formation in primary human hepatic
      stellate cells (HSCs), as well as the expression of alpha-SMA, collagen I and
      TIMP1 in both primary HSC and in a CCl4-induced fibrosis mouse model. S3I-201
      induced both apoptosis and cell cycle arrest in the HSC cell line (LX-2). S3I-201
      inhibited the expression of fibrogenesis factors TGFbeta1 and TGFbetaRII, as well
      as the downstream phosphorylation of Smad2, Smad3, Akt and ERK induced by
      TGFbeta1. In addition to fibrogenesis, both in vitro and in vivo assays showed
      that S3I-201 inhibited angiogenesis through expression suppression of VEGF and
      VEGFR2. Moreover, S3I-201 also had a synergistic effect with sorafenib, an FDA
      approved liver cancer drug, in the proliferation, apoptosis, angiogenesis and
      fibrogenesis of HSC. S3I-201 suppressed liver fibrosis through multiple
      mechanisms, and combined with sorafenib, S3I-201 could be a potentially effective
      antifibrotic agent.

PMID- 30206313
TI  - Application of ex-vivo spheroid model system for the analysis of senescence and
      senolytic phenotypes in uterine leiomyoma.
AB  - Cellular senecence is an important biologic endpoint. Naturally occuring (aging)
      senescence is common in uterine leiomyoma (ULM). AKT is one of major pathways in
      promoting ULM growth and survival. Inactivation of AKT by MK2206 in ULM resulted
      in stress-induced senescence in vitro. Study of the senescent phenotypes and
      molecular changes in ULM may greatly facilitate the understanding of the tumor
      biology and potential clinical therapy for this common disease associated with
      high morbidity. To study senescence in a model system that closely resembles
      primary ULM in vivo, we applied an ex vivo model of three-dimensional (3D)
      spheroid culture system which maintained the molecular and cellular
      characteristics of primary ULM and matched myometrium as seen in vivo. Gene
      expression profiling done on ULM induced to undergo replication (passaging) or
      stress-induced (MK2206) senescence revealed that ROS and hypoxic-related genes
      were upregulated in the two types of senescences. Overexpression of two selected
      genes, WIPI1 and SLITKR4, induced cellular senescence in ULM spheroids.
      Additionally, administration of ABT263 (a BH3 mimetic) effectively reduced the
      senescent cells induced in ULM spheroids. This study identified novel genes
      associated with senescence in ULM and demonstrated a BH3 mimetic to act as a
      senolytic to remove senescent cells.

PMID- 30206314
TI  - Western-type diet differentially modulates osteoblast, osteoclast, and lipoblast
      differentiation and activation in a background of APOE deficiency.
AB  - During the past few years, considerable evidence has uncovered a strong
      relationship between fat and bone metabolism. Consequently, alterations in plasma
      lipid metabolic pathways strongly affect bone mass and quality. We recently
      showed that the deficiency of apolipoprotein A-1 (APOA1), a central regulator of
      high-density lipoprotein cholesterol (HDL-C) metabolism, results in reduced bone
      mass in C57BL/6 mice. It is documented that apolipoprotein E (APOE), a
      lipoprotein know for its atheroprotective functions and de novo biogenesis of HDL
      C, is associated with the accumulation of fat in the liver and other organs and
      regulates bone mass in mice. We further studied the mechanism of APOE in bone
      metabolism using well-characterized APOE knockout mice. We found that bone mass
      was remarkably reduced in APOE deficient mice fed Western-type diet (WTD)
      compared to wild type counterparts. Static (microCT-based) and dynamic
      histomorphometry showed that the reduced bone mass in APOEpsilon-/- mice is
      attributed to both decreased osteoblastic bone synthesis and elevated
      osteoclastic bone resorption. Interestingly, histologic analysis of femoral
      sections revealed a significant reduction in the number of bone marrow lipoblasts
      in APOEpsilon-/- compared to wild type mice under WTD. Analyses of whole bone
      marrow cells obtained from femora of both animal groups showed that APOE null
      mice had significantly reduced levels of the osteoblastic (RUNX2 and Osterix) and
      lipoblastic (PPARgamma and CEBPalpha) cardinal regulators. Additionally, the
      modulators of bone remodeling RANK, RANKL, and cathepsin K were greatly
      increased, while OPG and the OPG/RANKL ratio were remarkably decreased in
      APOEpsilon-/- mice fed WTD, compared to their wild-type counterparts. These
      findings suggest that APOE deficiency challenged with WTD reduces osteoblastic
      and lipoblastic differentiation and activity, whereas it enhances osteoclastic
      function, ultimately resulting in reduced bone mass, in mice.

PMID- 30206315
TI  - T cells under starter's orders.

PMID- 30206316
TI  - A sugar sweet new treatment for erectile dysfunction after radical prostatectomy.

PMID- 30206318
TI  - Multipoint targeting of TGF-beta/Wnt transactivation circuit with microRNA 384-5p
      for cardiac fibrosis.
AB  - Cardiac fibrosis is a common precursor to ventricular dysfunction and eventual
      heart failure, and cardiac fibrosis begins with cardiac fibroblast activation.
      Here we have demonstrated that the TGF-beta signaling pathway and Wnt signaling
      pathway formed a transactivation circuit during cardiac fibroblast activation and
      that miR-384-5p is a key regulator of the transactivation circuit. The results of
      in vitro study indicated that TGF-beta activated an auto-positive feedback loop
      by increasing Wnt production in cardiac fibroblasts, and Wnt neutralizing
      antibodies disrupted the feedback loop. Also, we demonstrated that miR-384-5p
      simultaneously targeted the key receptors of the TGF-beta/Wnt transactivation
      circuit and significantly attenuated both TGF-beta-induced cardiac fibroblast
      activation and ischemia-reperfusion-induced cardiac fibrosis. In addition, small
      molecule that prevented pro-fibrogenic stimulus-induced downregulation of
      endogenous miR-384-5p significantly suppressed cardiac fibroblast activation and
      cardiac fibrosis. In conclusion, modulating a key endogenous miRNA targeting
      multiple components of the TGF-beta/Wnt transactivation circuit can be an
      effective means to control cardiac fibrosis and has great therapeutic potential.

PMID- 30206317
TI  - Natural variation among Arabidopsis thaliana accessions in tolerance to high
      magnesium supply.
AB  - High magnesium (Mg2+) in some extreme serpentine soils or semi-arid regions is an
      important factor affecting crop growth and development. Specific loci that form
      the genetic framework underlying high Mg2+ homeostasis, however, are not well
      understood. By using GWA mapping on 388 accessions of Arabidopsis thaliana
      selected from a worldwide collection and genotyped at approximately 250,00 SNPs,
      we successfully identified 109 and 74 putative genetic regions associated in
      nutrient traits under normal (1,000 uM) and high Mg2+ (10,000 uM), respectively.
      Above 90% SNPs associated with nutrients including Mg2+ and only two SNPs shared
      between normal and high Mg2+. A single strong peak of SNPs associated with Ca
      concentration corresponding to candidate gene At1g60420 ARABIDOPSIS NUCLEOREDOXIN
      (AtNRX1) under high Mg2+ was further determined. Compared with wildtype, mutants
      of Atnrx1-1 and Atnrx1-2 supplied with high Mg2+ had higher Ca concentrations in
      the plant, and higher cytosolic Ca2+ concentrations during root elongation, as
      well as higher fresh weight and lateral-root number. This suggests that AtNRX1
      was a critical gene negatively regulating Ca uptake under high Mg2+ conditions.
      The discovery could help to breed/select crops that can adapt to high-Mg2+ soils
      such as serpentine soils (high ratio of Mg2+: Ca2+) or Mars soil with high levels
      of magnesium sulfate.

PMID- 30206319
TI  - Molecular basis of dimerization of initiator caspase was revealed by crystal
      structure of caspase-8 pro-domain.
AB  - The assembly of death-inducing signaling complex (DISC) for activation of
      initiator caspase is a key step for the receptor-mediated apoptosis signaling.
      Many death effector domain (DED)-containing proteins are involved in DISC
      assembly and controlling. One of the main DISC component, caspase-8, contains DED
      and DED-mediated dimerization and oligomerization in the DISC is critical for the
      activation of this initiator caspase. There have been intensive studies to
      understand DED-mediated dimerization and oligomerization for the DISC assembly
      but no clear answer has been provided and there are many controversial arguments.
      Here, we suggested novel dimerization process of tandem DED of caspase-8 with
      crystallographic study.

PMID- 30206321
TI  - Huntington disease - a neurodevelopmental disorder?

PMID- 30206320
TI  - High-density SNP-based QTL mapping and candidate gene screening for yield-related
      blade length and width in Saccharina japonica (Laminariales, Phaeophyta).
AB  - Saccharina japonica is one of the most important marine crops in China, Japan and
      Korea. Candidate genes associated with blade length and blade width have not yet
      been reported. Here, based on SLAF-seq, the 7627 resulting SNP loci were selected
      for genetic linkage mapping to 31 linkage groups with an average spacing of 0.69
      cM, and QTL analyses were performed to map the blade length and blade width
      phenotypes of S. japonica. In total, 12 QTLs contributing to blade length and 10
      to width were detected. Some QTL intervals were detected for both blade length
      and width. Additive alleles for increasing blade length and width in S. japonica
      came from both parents. After the QTL interval regions were comparatively mapped
      to the current reference genome of S. japonica (MEHQ00000000), 14 Tic20
      (translocon on the inner envelope membrane of chloroplast) genes and three
      peptidase genes were identified. RT-qPCR analysis showed that the transcription
      levels of four Tic20 genes were different not only in the two parent sporophytes
      but also at different cultivation times within one parent. The SNP markers
      closely associated with blade length and width could be used to improve the
      selection efficiency of S. japonica breeding.

PMID- 30206322
TI  - Impact of obstructive sleep apnea on long-term blood pressure variability in
      Japanese men: a cross-sectional study of a work-site population.
AB  - Blood pressure variability (BPV) has been shown to be associated with
      cardiovascular diseases. The effects on long-term BPV of obstructive sleep apnea
      (OSA) are not yet known. We evaluated a total of 1653 Japanese male workers (18
      69 years) at a work site to diagnose OSA, and we divided them into three groups:
      non-OSA (apnea-hypopnea index (AHI): < 5, n = 1414), mild-to-moderate OSA (5 <=
      AHI < 30: n = 131) and severe OSA (AHI >= 30: n = 108). The standard deviation
      and coefficient of variation of the subjects' BPV were calculated by using their
      annual blood pressure measurements at routine physical examinations from 2012 to
      2015 (four measurements). The multivariable-adjusted BPV of systolic blood
      pressure (SBP) was significantly higher in the severe-OSA group compared to the
      non-OSA group. A multiple regression analysis also revealed that OSA was
      positively associated with BPV of SBP. We focused on the mild-to-moderate OSA
      group to evaluate the association of OSA treatment with BPV, because most of the
      severe-OSA subjects were being treated with continuous positive airway pressure
      or an oral appliance. The BPV of both systolic and diastolic blood pressure was
      significantly decreased in the treated subjects. These findings suggest that OSA
      is associated with increases in long-term BPV which was improved by the treatment
      of OSA in Japanese men of a work-site population.

PMID- 30206323
TI  - Microvascular endothelial function is impaired in patients with idiopathic
      hyperaldosteronism.
AB  - The aims were to evaluate the relationship between idiopathic hyperaldosteronism
      (IHA) and grade of vascular function in the macrovasculature and
      microvasculature. Vascular function, including reactive hyperemia index (RIH),
      flow-mediated vasodilation (FMD), and nitroglycerine-induced vasodilation (NID)
      were evaluated in 52 patients with IHA, 53 patients with aldosterone-producing
      adenoma (APA), and 52 age-, sex-, and blood pressure-matched patients with
      essential hypertension (EHT). Log RHI was lower in the IHA and APA groups than in
      the EHT group (0.54 +/- 0.25 and 0.55 +/- 0.23 versus 0.79 +/- 0.28; P < 0.01,
      respectively). FMD was lower in the APA group than in the EHT group (3.4 +/- 2.1%
      versus 4.8 +/- 2.8%; P = 0.02), whereas there was no significant difference in
      FMD between the IHA and the APA and EHT groups. NID was lower in the APA group
      than in the EHT group (10.0 +/- 4.5% versus 12.5 +/- 5.7%; P = 0.03), whereas
      there was no significant difference in NID between the IHA, APA, and EHT groups.
      Multiple regression analysis revealed an association of log RHI with plasma
      aldosterone concentration (t = -2.24; P = 0.03) and an association of FMD with
      plasma aldosterone concentration (t = -3.07; P < 0.01). Microvascular endothelial
      function was impaired in patients with IHA compared with that in patients with
      EHT.

PMID- 30206326
TI  - Planning a path.

PMID- 30206325
TI  - Catching waves.

PMID- 30206324
TI  - Central and peripheral blood pressure response to a single bout of an exercise
      session in patients with resistant hypertension.

PMID- 30206327
TI  - Novel inhibition.

PMID- 30206328
TI  - Microglial signatures and their role in health and disease.
AB  - Microglia are the primary innate immune cells in the CNS. In the healthy brain,
      they exhibit a unique molecular homeostatic 'signature', consisting of a specific
      transcriptional profile and surface protein expression pattern, which differs
      from that of tissue macrophages. In recent years, there have been a number of
      important advances in our understanding of the molecular signatures of
      homeostatic microglia and disease-associated microglia that have provided insight
      into how these cells are regulated in health and disease and how they contribute
      to the maintenance of the neural environment.

PMID- 30206329
TI  - Untangling tau structure.

PMID- 30206330
TI  - Inflammasome signalling in brain function and neurodegenerative disease.
AB  - The mammalian CNS is an intricate and fragile structure, which on one hand is
      open to change in order to store information, but on the other hand is vulnerable
      to damage from injury, pathogen invasion or neurodegeneration. During senescence
      and neurodegeneration, activation of the innate immune system can occur.
      Inflammasomes are signalling complexes that regulate cells of the immune system,
      which in the brain mainly includes microglial cells. In microglia, the NLRP3 (NOD
      , LRR- and pyrin domain-containing 3) inflammasome becomes activated when these
      cells sense proteins such as misfolded or aggregated amyloid-beta, alpha
      synuclein and prion protein or superoxide dismutase, ATP and members of the
      complement pathway. Several other inflammasomes have been described in microglia
      and the other cells of the brain, including astrocytes and neurons, where their
      activation and subsequent caspase 1 cleavage contribute to disease development
      and progression.

PMID- 30206331
TI  - Strength and Performance Enhancement of Multilayers by Spatial Tailoring of
      Adherend Compliance and Morphology via Multimaterial Jetting Additive
      Manufacturing.
AB  - Material tailoring of bondlayer compliance is a known effective route to enhance
      performance of multilayers, and here spatial material-tailoring of compliance and
      morphology of the adherends is examined. Multimaterial jetting additive
      manufacturing (AM) allows us to realize for the first time compliance- and
      morphology-tailored adherends, and evaluate directly the mechanical performance,
      including failure, of the tensile-loaded multilayers. Adherend compliance
      tailoring, unlike bondlayer tailoring, requires additional consideration due to
      adherend bending stiffness and moment influences on bondlayer stresses. We
      introduce anisotropic as well as layered/sandwich adherend tailoring to address
      this dependence. Numerical models show that for both sub-critical and critical
      bondlengths (at which shear-dominated load transfer occurs through the
      bondlayer), adherend tailoring reduces peak stresses significantly, particularly
      peel stress (reductions of 47-80%) that typically controls failure in such
      systems. At sub-critical bondlengths, the AM-enabled layered/sandwich adherend
      tailoring shows significantly increased experimental performance over the
      baseline multilayer: strength is increased by 20%, toughness by 48%, and strain
      to-break by 18%, while retaining multilayer stiffness. The adherend tailoring
      demonstrated here adds to the techniques available to increase the performance of
      bonded multilayers, suggesting that adherend tailoring is particularly well
      suited to additively manufactured multilayers, but can also have application in
      other areas such as layered electronics and advanced structural composite
      laminates.

PMID- 30206332
TI  - Determinants of leptin in human breast milk: results of the Ulm SPATZ Health
      Study.
AB  - BACKGROUND: Leptin in human breast milk has been implicated as a potential
      regulator of early-life metabolic programming. We comprehensively investigated
      the influence of maternal body mass index (BMI) and non-adiposity associated
      determinants on breast milk leptin concentration at 6 weeks, 6 months, and 1 year
      postpartum. METHODS: The Ulm SPATZ Health Study consists of 1006 newborns and
      their mothers recruited from the general population in the University Medical
      Center Ulm, Southern Germany, in 2012/2013. Leptin concentration was measured in
      skimmed breast milk using commercially available ELISA (R&D System). Generalized
      estimating equations (GEE) accounting for repeated measures were used to
      calculate beta coefficients and 95% confidence intervals for association of
      potential demographic and lifestyle related determinants of hormone concentration
      with BMI-standardized leptin z-scores. RESULTS: Leptin concentration was measured
      in breast milk samples obtained from 694 mothers at approximately 6 weeks (n =
      668), 6 months (n = 445), and 1 year (n = 69) postpartum. Differences in crude
      leptin concentrations between collection times were mostly explained by changes
      in BMI, breastfeeding frequency, and breast milk fat concentration. Positive
      associations between BMI and leptin were nonlinear and stronger among lower BMI
      subjects. Upon standardization, residual leptin concentrations were associated
      with maternal birth country, parity, age, and smoking history. CONCLUSIONS:
      Breast milk leptin concentration is primarily determined by adiposity-related
      factors. Studies using BMI as a proxy measure for adiposity should account for an
      observed nonlinear association with leptin, which may be especially important in
      determining causal associations with health outcomes from this and other
      adiposity-related hormones in breast milk.

PMID- 30206333
TI  - Prospective associations between social vulnerabilities and children's weight
      status. Results from the IDEFICS study.
AB  - BACKGROUND/OBJECTIVES: In high-income countries, childhood obesity follows a
      clear socioeconomic gradient with greater prevalence in children with lower
      socioeconomic status (SES). The extent to which the trend of other social
      vulnerabilities over time and the accumulation of these vulnerabilities can
      affect children's weight is still unknown. SUBJECTS/METHODS: In the IDEFICS
      study, 8624 children aged 2.0-9.9 years from eight European countries were
      examined at baseline and after 2 years. Sociodemographic variables, maternal body
      mass index (BMI), and lifestyle were reported by parents. Children were measured
      and classified as thin, normal weight, and overweight/obese using the extended
      IOTF criteria. Four vulnerable groups were defined: children whose parents were
      migrants, children whose parents lack a social network, children from non
      traditional families (children not living with both biological parents), and
      children with unemployed parents. Logistic mixed-effects models were used to
      study the association between vulnerabilities and children's weight at baseline
      and follow-up, temporal trends in vulnerabilities and children's weight and
      accumulation of vulnerabilities and children's weight. Models were adjusted for
      lifestyle, maternal BMI, parental education, and income. RESULTS: Children whose
      parents lost their social support at follow-up were more likely to be thin than
      non-vulnerable children (OR = 1.69, 99% CI = 1.03-2.78). Children whose parents
      had a migrant background (OR = 1.30, 99% CI 1.04-1.62), children from non
      traditional families at both time points (OR = 1.40, 99% CI 1.03-1.90) and whose
      parents were unemployed at baseline and follow-up (OR = 2.03, 99% CI 1.03-3.99)
      were more likely to be overweight/obese compared to non-vulnerable children.
      Cross-sectionally, we did not find an association between parental lack of
      network, non-traditional family structure, or employment and children's weight
      status. CONCLUSIONS: Policy actions are required to tackle inadequate weight loss
      and gain among vulnerable children (especially those exposed over the long term)
      since they are at a higher risk of thinness and overweight.

PMID- 30206334
TI  - Does a parsimonious measure of complex body mass index trajectories exist?
AB  - BACKGROUND: A single measure that distills complex body mass index (BMI)
      trajectories into one value could facilitate otherwise complicated analyses. This
      study creates and assesses the validity of such a measure: average excess BMI.
      METHODS: We use data from Waves I-IV of the National Longitudinal Study of
      Adolescent to Adult Health (n = 17,669). We calculate average excess BMI by
      integrating to find the area above a healthy BMI trajectory and below each
      subject-specific trajectory and divide this value by total study time. To assess
      validity and utility, we (1) evaluate relationships between average excess BMI
      from adolescence to adulthood and adult chronic conditions, (2) compare
      associations and fit to models using subject-specific BMI trajectory parameter
      estimates as predictors, and (3) compare associations to models using BMI
      trajectory parameter estimates as outcomes. RESULTS: Average excess BMI from
      adolescence to adulthood is associated with increased odds of hypertension (OR =
      1.56; 95% CI: 1.47, 1.67), hyperlipidemia (OR = 1.36; 95% CI: 1.26, 1.47), and
      diabetes (OR = 1.57; 95% CI: 1.47, 1.67). The odds associated with average excess
      BMI are higher than the odds associated with the BMI intercept, linear, or
      quadratic slope. Correlations between observed and predicted health outcomes are
      slightly lower for some models using average excess BMI as the focal predictor
      compared to those using BMI intercept, linear, and quadratic slope. When using
      trajectory parameters as outcomes, some co-variates associate with the intercept,
      linear, and quadratic slope in contradicting directions. CONCLUSIONS: This study
      supports the utility of average excess BMI as an outcome. The higher an
      individual's average excess BMI from adolescence to adulthood, the greater their
      odds of chronic conditions. Future studies investigating longitudinal BMI as an
      outcome should consider using average excess BMI, whereas studies that
      conceptualize longitudinal BMI as the predictor should continue using traditional
      latent growth methods.

PMID- 30206335
TI  - Effects of intermittent versus continuous dieting on weight and body composition
      in obese and overweight people: a systematic review and meta-analysis of
      randomized controlled trials.
AB  - BACKGROUND: Intermittent dieting may be an alternative to continuous dieting for
      weight reduction. OBJECTIVE: To evaluate the effect of intermittent dieting
      versus continuous dieting on weight and body composition in overweight or obese
      adults. DESIGN: A systematic review and meta-analysis of randomized controlled
      trials (RCTs). Five databases were searched until February 2018 for RCTs
      comparing intermittent versus continuous dieting. Intermittent dieting consisted
      of two types: regular intermittent was caloric restriction interspersed with days
      of weight maintenance or ad libitum eating; intensified intermittent was caloric
      restriction interspersed with days of even lower caloric restriction. Continuous
      was continual caloric restriction. Primary outcomes were weight, body fat, lean
      mass, waist circumference, hip circumference, and energy expenditure. Data were
      pooled by the inverse variance method using random-effects models and expressed
      as mean differences (MD) and their 95% confidence intervals (CI). RESULTS: Nine
      trials met the inclusion criteria (n = 782), six comparing regular intermittent
      vs continuous (n = 553), and three comparing intensified intermittent vs
      continuous (n = 229). Populations were heterogeneous: obese only in five studies,
      and overweight or obese (mixed) in four studies. Lean mass was significantly
      lower in regular intermittent vs continuous (MD -0.86 kg; 95% CI -1.62 to -0.10;
      p = 0.03). No differences were found for the remaining outcomes for both
      comparisons (regular intermittent or intensified intermittent vs continuous).
      There was low heterogeneity of effects across trials. Subgroup effects by time to
      follow-up, gender, per-protocol versus intention-to-treat, enforced exercise, and
      diabetes were similar to main analyses. CONCLUSIONS: This systematic review in
      obese and overweight individuals showed that regular intermittent dieting
      decreased lean mass compared to continuous dieting. There were no differences in
      effects for either intermittent vs continuous interventions across all other
      outcomes. In contrast to previous systematic reviews, this study suggested that
      lean mass is better preserved in continuous dieting compared to regular
      intermittent dieting.

PMID- 30206336
TI  - Salt in stools is associated with obesity, gut halophilic microbiota and
      Akkermansia muciniphila depletion in humans.
AB  - BACKGROUND/OBJECTIVES: High salt intake has been linked to several diseases
      including obesity and an increased risk of death; however, fecal salinity and the
      ability of salt to alter the gut microbiota, which was recently identified as an
      instrumental factor for health and disease, remains poorly explored.
      METHODS/SUBJECTS: We analyzed the fecal samples of 1326 human individuals for
      salinity by refractometry, 572 for gut microbiota by culturomics, and 164 by 16S
      rRNA-targeted metagenomics. Geographical origin, age, gender, and obesity were
      tested as predictors of fecal salinity and halophilic diversity. All halophilic
      isolates were characterized by taxonogenomics and their genome sequenced.
      RESULTS: Fecal salinity was associated with obesity independently of geographical
      origin, gender, and age. The first 2 human-associated halophilic archaeal members
      were isolated along with 64 distinct halophilic species, including 21 new species
      and 41 known in the environment but not in humans. No halophiles grow in less
      than 1.5% salinity. Above this threshold, the richness of the halophilic
      microbiota was correlated with fecal salinity (r = 0.58, p < 0.0001). 16S
      metagenomics linked high fecal salinity to decreased diversity (linear
      regression, p < .035) and a depletion in anti-obesity Akkermansia muciniphila and
      Bifidobacterium, specifically B. longum and B. adolescentis. Genomics analysis
      suggested that halophilic microbes are not only transient passengers but may be
      residents of the human gut. CONCLUSIONS: High salt levels are associated with
      alteration of the gut microbial ecosystem and halophilic microbiota, as
      discovered during this study. Further studies should clarify if the gut
      microbiota alterations associated with high salt levels and the human halophilic
      microbiota could be causally related to human disease, such as obesity.

PMID- 30206337
TI  - Adipose tissue TSH as a new modulator of human adipocyte mitochondrial function.
AB  - BACKGROUND/OBJECTIVES: Recent studies indicate a possible role of TSH/TSHR
      signalling axis on adipogenesis and adipose tissue physiology. Here, we aimed to
      investigate the relationship between adipose tissue TSHB and adipose tissue
      physiology-related gene expression. SUBJECTS/METHODS: Subcutaneous and visceral
      adipose tissue TSHB gene expression was analysed in two independent cohorts
      [Cohort1 (N = 96) and Cohort2 (N = 45)] and after bariatric surgery-induced
      weight loss [Cohort3 (N = 22)]. Adipose tissue TSH protein expression was also
      analysed in a subgroup of participants from Cohort 1 (N = 16). The effects of
      recombinant TSH on human subcutaneous preadipocytes and adipocytes were
      investigated. RESULTS: In cohort 1, both visceral and subcutaneous adipose tissue
      TSHB gene expression was positively correlated with the expression of
      mitochondrial function (PPARGC1A, ISCA2, CISD1, SIRT1, NFE2L2, NRF1) and fatty
      acid mobilization (CAV1, ENGL1), but not with adipogenic-related genes. Of note,
      adipose tissue TSH protein levels were also associated with some of these markers
      of mitochondrial function and fatty acid mobilization. These associations were
      replicated in cohort 2. Bariatric surgery-induced weight loss resulted in
      increased subcutaneous adipose tissue TSHB in parallel to increased PPARGC1A. In
      human subcutaneous adipocytes, rh-TSH administration led to increased
      mitochondrial respiratory capacity in parallel to increased mitochondrial
      function- and adipogenic-related gene expression, but no significant effects were
      observed during differentiation of human preadipocytes. CONCLUSION: These data
      point to a possible role of adipose tissue TSH in the maintenance of adipocyte
      mitochondrial function.

PMID- 30206338
TI  - Visceral fat-related systemic inflammation and the adolescent brain: a mediating
      role of circulating glycerophosphocholines.
AB  - OBJECTIVE: Life-long maintenance of brain health is important for the prevention
      of cognitive impairment in older age. Low-grade peripheral inflammation
      associated with excess visceral fat (VF) may influence brain structure and
      function. Here we examined (i) if this type of inflammation is associated with
      altered white-matter (WM) microstructure and lower cognitive functioning in
      adolescents, and (ii) if recently identified circulating glycerophosphocholines
      (GPCs) can index this type of inflammation and associated variations in WM
      microstructure and cognitive functioning. SUBJECTS: We studied a community-based
      sample of 872 adolescents (12-18 years, 48% males) in whom we assessed VF and WM
      microstructure with magnetic resonance imaging, processing speed with cognitive
      testing, serum C-reactive protein (CRP, a common marker of peripheral
      inflammation) with a high-sensitivity assay, and serum levels of a panel of 64
      GPCs with advanced mass spectrometry. RESULTS: VF was associated with CRP, and
      CRP in turn was associated with "altered" WM microstructure and lower processing
      speed (all p < 0.003). Further, "altered" WM microstructure was associated with
      lower processing speed (p < 0.0001). Of all 64 tested GPCs, 4 were associated
      with both VF and CRP (at Bonferroni corrected p < 0.0004). One of them,
      PC16:0/2:0, was also associated with WM microstructure (p < 0.0001) and
      processing speed (p = 0.0003), and mediated the directed associations between VF
      and both WM microstructure (p < 0.0001) and processing speed (p = 0.02). As a
      mediator, PC16:0/2:0 explained 21% of shared variance between VF and WM
      microstructure, and 22% of shared variance between VF and processing speed.
      Similar associations were observed in an auxiliary study of 80 middle-aged
      adults. CONCLUSIONS: Our results show that VF-related peripheral inflammation is
      associated with "altered" WM microstructure and lower cognitive functioning
      already in adolescents, and a specific circulating GPC may be a new molecule
      indexing this VF-related peripheral inflammation and its influences on brain
      structure and function.

PMID- 30206339
TI  - HLA and kidney disease: from associations to mechanisms.
AB  - Since the first association between HLA and diseases of native kidneys was
      described almost 50 years ago, technological and conceptual advances in HLA
      biology and typing, together with better case ascertainment, have led to an
      improved understanding of HLA associations with a variety of renal diseases. A
      substantial body of evidence now supports the existence of HLA genetic
      associations in the field of renal disease beyond the role of HLA in allogeneic
      responses in transplant recipients. Allomorphs of HLA have emerged as important
      risk factors in most immune-mediated renal diseases, which, together with other
      genetic and environmental factors, lead to loss of tolerance and autoimmune
      mediated renal inflammation. HLA associations have also been described for renal
      diseases that are less traditionally seen as autoimmune or immune-mediated. Here,
      we review essential concepts in HLA biology and the association of HLA with
      diseases of the native kidneys, and describe the current understanding of the
      epistatic and mechanistic bases of HLA-associated kidney disease. Greater
      understanding of the relationship between HLA and kidney function has the
      potential not only to further the understanding of immune renal disease at a
      fundamental level but also to lead to the development and application of more
      effective, specific and less toxic therapies for kidney diseases.

PMID- 30206340
TI  - Author Correction: Matrix metalloproteinase-9 activity and a downregulated
      Hedgehog pathway impair blood-brain barrier function in an in vitro model of CNS
      tuberculosis.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has not been fixed in the paper.

PMID- 30206343
TI  - Automatic detection and counting of urediniospores of Puccinia striiformis f. sp.
      tritici using spore traps and image processing.
AB  - The quantitative monitoring of airborne urediniospores of Puccinia striiformis f.
      sp. tritici (Pst) using spore trap devices in wheat fields is an important
      process for devising strategies early and effectively controlling wheat stripe
      rust. The traditional microscopic spore counting method mainly relies on naked
      eye observation. Because of the great number of trapped spores, this method is
      labour intensive and time-consuming and has low counting efficiency, sometimes
      leading to huge errors; thus, an alternative method is required. In this paper, a
      new algorithm was proposed for the automatic detection and counting of
      urediniospores of Pst, based on digital image processing. First, images of
      urediniospores were collected using portable volumetric spore traps in an indoor
      simulation. Then, the urediniospores were automatically detected and counted
      using a series of image processing approaches, including image segmentation using
      the K-means clustering algorithm, image pre-processing, the identification of
      touching urediniospores based on their shape factor and area, and touching
      urediniospore contour segmentation based on concavity and contour segment
      merging. This automatic counting algorithm was compared with the watershed
      transformation algorithm. The results show that the proposed algorithm is
      efficient and accurate for the automatic detection and counting of trapped
      urediniospores. It can provide technical support for the development of online
      airborne urediniospore monitoring equipment.

PMID- 30206342
TI  - Exploratory analysis of the human breast DNA methylation profile upon soymilk
      exposure.
AB  - Upon soy consumption, isoflavone metabolites attain bioactive concentrations in
      breast tissue possibly affecting health. Though in vitro epigenetic activity of
      soy metabolites has been described, the in vivo impact on the epigenome is
      largely unknown. Therefore, in this case-control study, the breast glandular
      tissue DNA methylome was explored in women undergoing an aesthetic breast
      reduction. After a run-in phase, 10 generally healthy Belgian or Dutch women
      received soymilk for 5 days. MethylCap-seq methylation profiles were compared
      with those of 10 matched controls. Isoflavones and their microbial metabolites
      were quantified in urine, serum, and glandular breast tissue (liquid
      chromatography-mass spectrometry) and 17beta-estradiol in glandular breast tissue
      (immunoassay). Global DNA methylation levels were obtained for 6 cases and 5
      controls using liquid chromatography-mass spectrometry. Although lower MethylCap
      seq coverages were observed, mass spectrometry results and computational LINE-1
      methylation analysis did not provide evidence supporting global methylation
      alterations upon treatment. At a false discovery rate of 0.05, no differentially
      methylated loci were identified. Moreover, a set of previously identified loci
      was specifically tested, but earlier reported results could not be validated. In
      conclusion, after a 5-day soymilk treatment, no major general epigenetic
      reprogramming in breast tissue could be found in this exploratory study.

PMID- 30206344
TI  - Author Correction: Anti-trypanosomatid drug discovery: an ongoing challenge and a
      continuing need.
AB  - The structures of nifurtimox in Table 1 were incorrect and have been updated in
      the pdf and online. The authors apologize for any confusion caused.

PMID- 30206346
TI  - Does fluid restriction improve outcomes in infants with hypoxic ischemic
      encephalopathy? A pilot randomized controlled trial.
AB  - OBJECTIVE: To evaluate whether a strategy of restricted fluid intake in the first
      4 days reduces mortality and morbidity among term neonates with moderate to
      severe hypoxic ischemic encephalopathy (HIE) treated with therapeutic
      hypothermia. STUDY DESIGN: Eighty neonates with HIE were randomized between
      January 2016 and February 2018 to receive normal fluid intake (n = 40) or
      restricted fluid intake (two-third of normal intake; n = 40) in the first 4 days
      of life. The primary outcome was a composite of death or major neurodevelopmental
      disability at 6 months of age. RESULTS: The primary outcome occurred in 10
      infants (26%) in the fluid-restricted group and 3 infants (8%) in the normal
      fluid intake group, but the difference was not statistically significant (p =
      0.065). Five infants in the fluid-restricted group had hypoglycemia (p = 0.055).
      CONCLUSION: Restricted fluid intake did not reduce the composite outcome of death
      or neurodevelopmental disability and was associated with a trend toward more
      hypoglycemia.

PMID- 30206341
TI  - Evidence for Regulation of Hemoglobin Metabolism and Intracellular Ionic Flux by
      the Plasmodium falciparum Chloroquine Resistance Transporter.
AB  - Plasmodium falciparum multidrug resistance constitutes a major obstacle to the
      global malaria elimination campaign. Specific mutations in the Plasmodium
      falciparum chloroquine resistance transporter (PfCRT) mediate resistance to the 4
      aminoquinoline drug chloroquine and impact parasite susceptibility to several
      partner agents used in current artemisinin-based combination therapies, including
      amodiaquine. By examining gene-edited parasites, we report that the ability of
      the wide-spread Dd2 PfCRT isoform to mediate chloroquine and amodiaquine
      resistance is substantially reduced by the addition of the PfCRT L272F mutation,
      which arose under blasticidin selection. We also provide evidence that L272F
      confers a significant fitness cost to asexual blood stage parasites. Studies with
      amino acid-restricted media identify this mutant as a methionine auxotroph.
      Metabolomic analysis also reveals an accumulation of short, hemoglobin-derived
      peptides in the Dd2 + L272F and Dd2 isoforms, compared with parasites expressing
      wild-type PfCRT. Physiologic studies with the ionophores monensin and nigericin
      support an impact of PfCRT isoforms on Ca2+ release, with substantially reduced
      Ca2+ levels observed in Dd2 + L272F parasites. Our data reveal a central role for
      PfCRT in regulating hemoglobin catabolism, amino acid availability, and ionic
      balance in P. falciparum, in addition to its role in determining parasite
      susceptibility to heme-binding 4-aminoquinoline drugs.

PMID- 30206345
TI  - Prevalence and safety of diazoxide in the neonatal intensive care unit.
AB  - OBJECTIVE: Diazoxide is used to treat infants with persistent hypoglycemia, but
      the prevalence of its use and adverse effects are not well described. We report
      demographic and clinical characteristics of infants treated with diazoxide in
      neonatal intensive care units (NICUs). STUDY DESIGN: Retrospective cohort study
      of infants 24-41 weeks' gestation admitted to 392 NICUs from 1997-2016, comparing
      characteristics between hypoglycemic infants exposed/not exposed to diazoxide.
      For diazoxide courses > 1 day, we report percentages of infants starting
      diuretics and/or developing new ventilator/oxygen requirement during therapy.
      RESULTS: Among 1,249,466 infants, 185,832 had hypoglycemia; 1066/185,832 (0.57%)
      received diazoxide. Diazoxide use increased over time (P = 0.001). Infants
      receiving diazoxide varied from 0-14.9% among centers. New diuretic courses were
      associated with 91/664 (14%), and new oxygen or ventilator requirement during
      therapy was associated with 64/556 (12%) and 34/647 (5%), respectively.
      CONCLUSIONS: Diazoxide use in NICU settings has increased over time. Infants
      receiving diazoxide commonly received diuretics.

PMID- 30206347
TI  - Initial hematocrit values after birth and peri/intraventricular hemorrhage in
      extremely low birth weight infants.
AB  - OBJECTIVE: Ischemia followed by reperfusion plays a significant role in the
      pathogenesis of peri/intraventricular hemorrhage (P/IVH). Delayed cord clamping
      promotes placental transfusion to newborn and is associated with decreased P/IVH.
      We hypothesized that extremely low birth weight (ELBW) infants with higher
      initial hematocrit (Hct) after birth are less likely to develop P/IVH. STUDY
      DESIGN: Pre- and postnatal data on inborn ELBW infants over 7 years were
      reviewed. We examined the relationship between P/IVH in the first week and
      initial Hct using logistic regression modeling. RESULTS: We studied 225 infants
      with a median gestational age (GA) 25.7 (22.4-31.7). Forty-one percent had grade
      I-IV P/IVH. In univariate analysis, cesarean section (CS) and higher GA, birth
      weight, 5-minute Apgar, and initial Hct were associated with decreased likelihood
      of P/IVH while higher maximum PCO2 in first 3 days and use of
      inotropes/vasopressors, postnatal steroid for hypotension, hypernatremia,
      transfusion, and use of insulin for hyperglycemia during the first week of life
      were associated with increased likelihood of P/IVH. In multiple regression
      analysis, only GA, CS, and initial Hct remained significantly associated with
      P/IVH. Adjusting for GA and CS, the odds of P/IVH was higher with Hct < 40% (OR
      2.04, 95% CI [1.11, 3.76]) and Hct < 45% (2.38 [1.19, 4.76]). CONCLUSION: Higher
      initial Hct is associated with decreased P/IVH. Initial Hct < 45% was associated
      with a 2-fold increase in P/IVH. We speculate that lower initial Hct represents a
      lower intravascular volume status and promotes cerebral hypoperfusion preceding
      P/IVH.

PMID- 30206348
TI  - Antenatal steroids and thyroid hormone function in preterm infants.
AB  - BACKGROUND: Antenatal steroids (ANS) are used widely for women at risk of preterm
      delivery. Evidence on the effects of ANS on thyroid hormone function in preterm
      infants is limited. OBJECTIVES: To determine effects of ANS on thyroid hormone
      function in preterm infants. METHODS: A retrospective cohort study of preterm
      infants born before 30 weeks of gestation. Infants were divided into no ANS,
      partial ANS, and complete ANS groups. Thyroid function tests at day of life 30
      were compared. RESULTS: 260 Infants were included. A significantly higher
      proportion of patients were started on levothyroxine (LT4) in no ANS group and
      partial ANS group compared to complete ANS group. Logistic regression analysis
      revealed that infants in no ANS group are more likely to have TSH > 6 MUIU ml-1
      and started on LT4 compared to complete ANS group. CONCLUSION: Infants in no ANS
      group are more likely to have thyroid dysfunction compared to complete ANS group.

PMID- 30206349
TI  - Genetic relatedness of Gram-negative bacteria colonizing gut and skin of neonates
      and mother's own milk.
AB  - OBJECTIVE: We described colonization of mother's own milk with Gram-negative
      bacteria and its relationship with neonatal colonization. STUDY DESIGN: Gram
      negative bacteria isolated from weekly collected stool, skin and mother's own
      milk of hospitalized preterm (n = 49) and healthy term neonates (n = 20) were
      genotyped. Colonization-related factors were determined by logistic regression.
      RESULTS: Gram-negative bacteria were isolated from mother's own milk of 22.4% (n
      = 11) and 15% (n = 3) of mothers of preterm and term neonates, respectively.
      According to pulsed-field gel electrophoresis genetically similar strains were
      present in mother's own milk and gut of 8.2% (n = 4) of mother-preterm neonate,
      but none of mother-term neonate pairs. In three of four late-onset sepsis caused
      by Gram-negative bacteria, colonization of gut, but not mother's own milk, with
      invasive species preceded late-onset sepsis. CONCLUSIONS: Colonization of
      mother's own milk with Gram-negative bacteria is uncommon and transmission to
      neonatal gut may occur in less than one-tenth of neonate-mother pairs.

PMID- 30206350
TI  - Low temperature synthesis of NbC/C nano-composites as visible light photoactive
      catalyst.
AB  - A facile carbothermal route was adopted to obtain niobium carbide nanoparticles
      (NPs) embedded in carbon network from Nb2O5 to study photocatalytic behavior.
      Optimization of synthesis parameters to obtain single phase NbC NPs has been
      successfully done. The phase identification, morphology and nature of carbon were
      determined with the help of X-ray diffraction, transmission electron microscopy
      (TEM) and Raman spectroscopy. X-ray photoelectron spectroscopy (XPS) suggested
      the presence of multiple oxidation states of Nb associated to NbC and NbCxOy
      centers on the surface of NPs. Due to the presence of NbCxOy on the surface of
      NPs, absorption under visible region of EM spectrum has been observed by UV
      visible spectroscopy. Different organic dyes (RhB, MB and MO) were used to study
      the effect of holding time on the photocatalytic performance of as-synthesized
      samples. RhB dye was found to be the most sensitive organic molecule among all
      the considered dyes and degraded 78% in 120 min.

PMID- 30206351
TI  - Reply to Sonmez et al.

PMID- 30206352
TI  - Genetic testing for DADA2: How can we avoid missing patients?

PMID- 30206353
TI  - Reverse pre-symptomatic testing for Huntington disease: double disclosure when
      25% at-risk children reveal the genetic status to their parent.
AB  - Predictive testing for Huntington disease (HD) in 25% at-risk individuals is
      testing with full knowledge, and sometimes assuming, that the parent does not
      want to know his status. The goal of this study was to understand: (1) the
      differences in the motivation between 25% and 50% at-risk individuals to be
      tested and (2) the consequences of "double disclosure", including parental
      reactions. Test requests from 25% at-risk individuals were rare (155/1611, 10%).
      We compared their motivation with those of 1456 50% at-risk individuals. The
      principal motivation to have the test for both groups was "to know" (48% versus
      58%, p = 0.049), but the desire to have children was more frequent in the 25% at
      risk group (32% versus 17%, p < 0.001). Sixty percent of the 25% at-risk group
      went through the testing procedure: 15% (n = 14) were variant positive for HD.
      Testees reported four adverse reactions of their parent (22%): one committed
      suicide and three became depressed. This result highlights the impact of "double
      disclosure", a bad result for the person themselves and the transmitting parent.
      It is the responsibility of the team to anticipate this outcome with the 25% at
      risk individuals: children revealing the genetic status to their parent. They
      should help the testees and their family to find a satisfactory solution to help
      prevent adverse reactions. This includes ensuring that the candidate is well
      infomed abour the testing options and consequences to her/himself but also to
      her/his parent. The at-risk parent should be offered to discuss the implications
      of their child's testing.

PMID- 30206354
TI  - Psychosocial and behavioral outcomes of genomic testing in cancer: a systematic
      review.
AB  - Psychosocial and behavioral outcomes of genetic testing in oncology are well
      known, however, it is unclear how these findings will generalize to more complex
      genomic testing. The aim of this systematic review was to assess the psychosocial
      and behavioral outcomes of cancer genomic testing. Studies were selected for
      inclusion if they were published from January 2003 to January 2017 and addressed
      psychological and behavioral outcomes of cancer genomic testing in adults. A
      review of four databases identified 9620 abstracts, with 22 publications meeting
      the inclusion criteria. Of the included articles, 11 studies reported on outcomes
      of germline testing, with three articles assessing panel testing and eight SNP
      testing. No studies assessed the outcomes of WGS or WES. Eleven articles assessed
      the outcomes of somatic testing, including testing for cancer prognosis and for
      personalized therapies. Studies were biased toward breast cancer and Caucasian
      women with high education and socioeconomic status. While studies demonstrated
      limited adverse psychological outcomes associated with genomic testing, a lack of
      consistency in psychosocial measures precluded any meta-analysis. Changes in
      health behavior following positive results were limited, and in some cases risk
      perception was not altered following genomic testing. There is limited evidence
      of adverse psychosocial outcomes and changes in health behavior following genomic
      testing to assess cancer risk. Findings from this review highlight the need for
      longitudinal research with superior methodological and theoretical design.

PMID- 30206355
TI  - A genome-wide search for new imprinted genes in the human placenta identifies
      DSCAM as the first imprinted gene on chromosome 21.
AB  - We identified, through a genome-wide search for new imprinted genes in the human
      placenta, DSCAM (Down Syndrome Cellular Adhesion Molecule) as a paternally
      expressed imprinted gene. Our work revealed the presence of a Differentially
      Methylated Region (DMR), located within intron 1 that might regulate the
      imprinting in the region. This DMR showed a maternal allele methylation,
      compatible with its paternal expression. We showed that DSCAM is present in
      endothelial cells and the syncytiotrophoblast layer of the human placenta. In
      mouse, Dscam expression is biallelic in foetal brain and placenta excluding any
      possible imprinting in these tissues. This gene encodes a cellular adhesion
      molecule mainly known for its role in neurone development but its function in the
      placenta remains unclear. We report here the first imprinted gene located on
      human chromosome 21 with potential clinical implications.

PMID- 30206356
TI  - MultiWaver 2.0: modeling discrete and continuous gene flow to reconstruct complex
      population admixtures.
AB  - Our goal in developing the MultiWaver software series was to be able to infer
      population admixture history under various complex scenarios. The earlier version
      of MultiWaver considered only discrete admixture models. Here, we report a newly
      developed version, MultiWaver 2.0, that implements a more flexible framework and
      is capable of inferring multiple-wave admixture histories under both discrete and
      continuous admixture models. MultiWaver 2.0 can automatically select an optimal
      admixture model based on the length distribution of ancestral tracks of
      chromosomes, and the program can estimate the corresponding parameters under the
      selected model. Specifically, for discrete admixture models, we used a likelihood
      ratio test (LRT) to determine the optimal discrete model and an expectation
      maximization algorithm to estimate the parameters. In addition, according to the
      principles of the Bayesian Information Criterion (BIC), we compared the optimal
      discrete model with several continuous admixture models. In MultiWaver 2.0, we
      also applied a bootstrapping technique to provide levels of support for the
      chosen model and the confidence interval (CI) of the estimations of admixture
      time. Simulation studies validated the reliability and effectiveness of our
      method. Finally, the program performed well when applied to real datasets of
      typical admixed populations, such as African Americans, Uyghurs, and Hazaras.

PMID- 30206357
TI  - Exploring rare and low-frequency variants in the Saguenay-Lac-Saint-Jean
      population identified genes associated with asthma and allergy traits.
AB  - The Saguenay-Lac-Saint-Jean (SLSJ) region is located in northeastern Quebec and
      is known for its unique demographic history and founder effect. As founder
      populations are enriched with population-specific variants, we characterized the
      variants distribution in SLSJ and compared it with four European populations
      (Finnish, Sweden, United Kingdom and France), of which the Finnish population is
      another founder population. Targeted sequencing of the coding and non-coding
      immune regulatory regions of the SLSJ asthma familial cohort and the four
      European populations were performed. Rare and low-frequency coding and non-coding
      regulatory variants identified in the SLSJ population were then investigated for
      variant- and gene-level associations with asthma and allergy-related traits
      (eosinophil percentage, immunoglobulin (Ig) E levels and lung function). Our data
      showed that (1) rare or deleterious variants were not enriched in the two founder
      populations as compared with the three non-founder European populations; (2) a
      larger proportion of founder population-specific variants occurred with higher
      frequencies; and (3) low-frequency variants appeared to be more deleterious.
      Furthermore, a rare variant, rs1386931, located in the 3'-UTR of CXCR6 and intron
      of FYCO1 was found to be associated with eosinophil percentage. Gene-based
      analyses identified NRP2, MRPL44 and SERPINE2 to be associated with various
      asthma and allergy-related traits. Our study demonstrated the usefulness of using
      a founder population to identify new genes associated with asthma and allergy
      related traits; thus better understand the genes and pathways implicated in
      pathophysiology.

PMID- 30206359
TI  - The cell cycle regulatory DREAM complex is disrupted by high expression of
      oncogenic B-Myb.
AB  - Overexpression of the oncogene MYBL2 (B-Myb) is associated with increased cell
      proliferation and serves as a marker of poor prognosis in cancer. However, the
      mechanism by which B-Myb alters the cell cycle is not fully understood. In
      proliferating cells, B-Myb interacts with the MuvB core complex including LIN9,
      LIN37, LIN52, RBBP4, and LIN54, forming the MMB (Myb-MuvB) complex, and promotes
      transcription of genes required for mitosis. Alternatively, the MuvB core
      interacts with Rb-like protein p130 and E2F4-DP1 to form the DREAM complex that
      mediates global repression of cell cycle genes in G0/G1, including a subset of
      MMB target genes. Here, we show that overexpression of B-Myb disrupts the DREAM
      complex in human cells, and this activity depends on the intact MuvB-binding
      domain in B-Myb. Furthermore, we found that B-Myb regulates the protein
      expression levels of the MuvB core subunit LIN52, a key adapter for assembly of
      both the DREAM and MMB complexes, by a mechanism that requires S28
      phosphorylation site in LIN52. Given that high expression of B-Myb correlates
      with global loss of repression of DREAM target genes in breast and ovarian
      cancer, our findings offer mechanistic insights for aggressiveness of cancers
      with MYBL2 amplification, and establish the rationale for targeting B-Myb to
      restore cell cycle control.

PMID- 30206361
TI  - Retroviral signature can predict therapy outcome.

PMID- 30206358
TI  - Effects of dichloroacetate as single agent or in combination with GW6471 and
      metformin in paraganglioma cells.
AB  - Paragangliomas (PGLs) are infiltrating autonomic nervous system tumors that cause
      important morbidity. At present, surgery is the only effective therapeutic option
      for this rare tumor. Thus, new agents for PGL treatment should be identified.
      Using unique PGL cell models established in our laboratory, we evaluated the
      effect of dichloroacetate (DCA) as single agent or in a novel combination with
      other metabolic drugs, including GW6471 and metformin. DCA and metformin had not
      been tested before in PGL. DCA reduced PGL cell viability and growth through
      mechanisms involving reactivation of PDH complex leading to promotion of
      oxidative metabolism, with lowering of lactate and enhanced ROS production. This
      resulted in cell cycle inhibition and induction of apoptosis in PGL cells, as
      shown by flow cytometry and immunoblot analyses. Moreover, DCA drastically
      impaired clonogenic activity and migration of PGL cells. Also metformin reduced
      PGL cell viability as single agent and the combinations of DCA, GW6471 and
      metformin had strong effects on cell viability. Furthermore, combined treatments
      had drastic and synergistic effects on clonogenic ability. In conclusion, DCA,
      GW6471 and metformin as single agents and in combination appear to have promising
      antitumor effects in unique cell models of PGL.

PMID- 30206360
TI  - Differential effects of spinal motor neuron-derived and skeletal muscle-derived
      Rspo2 on acetylcholine receptor clustering at the neuromuscular junction.
AB  - We recently reported that R-spondin 2 (Rspo2), a secreted activator of Wnt/beta
      catenin signaling, promotes acetylcholine receptor (AChR) clustering and
      neuromuscular junction (NMJ) formation via its receptor, Lgr5. Rspo2 is expressed
      highly in spinal motor neurons (SMNs) and marginally in the skeletal muscle, but
      the origin of Rspo2 at the NMJ remains elusive. We rescued Rspo2-deficient (Rspo2
      /-) mice by specifically expressing Rspo2 in the skeletal muscle and SMNs. SMN
      specific Rspo2 mitigated or over-corrected abnormal features of the NMJs and AChR
      clusters observed in Rspo2-/- mice including (i) abnormal broadening of enlarged
      AChR clusters, (ii) three of six abnormal ultrastructural features, and (iii)
      abnormal expression of nine genes in SMNs and the diaphragm. In contrast, muscle
      specific Rspo2 normalized all six abnormal ultrastructural features, but it had
      no effect on AChR clustering and NMJ formation at the light microscopy level or
      on abnormal gene expression in SMNs and the diaphragm. These results suggest that
      SMN-derived Rspo2 plays a major role in AChR clustering and NMJ formation in the
      postsynaptic region, and muscle-derived Rspo2 also plays a substantial role in
      juxtaposition of the active zones and synaptic folds.

PMID- 30206362
TI  - Changes in the midgut diverticula epithelial cells of the European cave spider,
      Meta menardi, under controlled winter starvation.
AB  - The European cave spider, Meta menardi, is among the most common troglophile
      species inhabiting the cave entrance zone in Europe, where prey is scarce in
      winter. Spiders feed only if prey is available; otherwise, they are subjected to
      long-term winter starvation. We carried out a four-month winter starvation of M.
      menardi under controlled conditions to analyze ultrastructural changes in the
      midgut diverticula epithelial cells at the beginning, in the middle and at the
      end of the starvation period. We used light microscopy, TEM and quantified
      reserve lipids and glycogen. The midgut diverticula epithelium consisted of
      secretory cells, digestive cells and adipocytes. During starvation, gradual
      vacuolization of some digestive cells, and some necrotic digestive cells and
      adipocytes appeared. Autophagic structures, autophagosomes, autolysosomes and
      residual bodies were found in all three cell types. Spherites and the energy
      reserve compounds were gradually exploited, until in some spherites only the
      membrane remained. Comparison between spring, autumn and winter starvation
      reveals that, during the growth period, M. menardi accumulate reserve compounds
      in spherites and protein granules, and energy-supplying lipids and glycogen, like
      many epigean, overwintering arthropods. In M. menardi, otherwise active all over
      the year, this is an adaptive response to the potential absence of prey in
      winter.

PMID- 30206363
TI  - Casein Kinase 1 Epsilon Regulates Glioblastoma Cell Survival.
AB  - Glioblastoma is the most common malignant brain cancer with a dismal prognosis.
      The difficulty in treating glioblastoma is largely attributed to the lack of
      effective therapeutic targets. In our previous work, we identified casein kinase
      1 epsilon (CK1epsilon, also known as CSNK1E) as a potential survival factor in
      glioblastoma. However, how CK1epsilon controls cell survival remains elusive and
      whether targeting CK1epsilon is a possible treatment for glioblastoma requires
      further investigation. Here we report that CK1epsilon was expressed at the
      highest level among six CK1 isoforms in glioblastoma and enriched in high-grade
      glioma, but not glia cells. Depletion of CK1epsilon remarkably inhibited the
      growth of glioblastoma cells and suppressed self-renewal of glioblastoma stem
      cells, while having limited effect on astrocytes. CK1epsilon deprivation
      activated beta-catenin and induced apoptosis, which was further counteracted by
      knockdown of beta-catenin. The CK1epsilon inhibitor IC261, but not PF-4800567,
      activated beta-catenin and blocked the growth of glioblastoma cells and
      glioblastoma stem cells. Congruently, IC261 elicited a robust growth inhibition
      of human glioblastoma xenografts in mice. Together, our results demonstrate that
      CK1epsilon regulates the survival of glioblastoma cells and glioblastoma stem
      cells through beta-catenin signaling, underscoring the importance of targeting
      CK1epsilon as an effective treatment for glioblastoma.

PMID- 30206365
TI  - One-way Acoustic Beam Splitter.
AB  - As a key component of various acoustic systems, acoustic beam splitter (BS) finds
      important application in many scenarios, yet are conventionally based on the
      assumption that the acoustic waves propagate as easily when incident from either
      input or output side. It would therefore be intriguing, from the viewpoints of
      both science and technology, to break through this limit by realizing acoustic
      BSs supporting asymmetric transmission. Here we propose the concept of one-way
      acoustic BS capable of splitting acoustic beam incident from the input port into
      multiple beams while effectively reducing the backward transmission from any of
      the output ports. Furthermore, our design enables flexibly adjusting the number
      and angle of output beams by blocking the unused line defects. The numerical
      results verify the theoretical predictions and demonstrate the phenomenon of one
      way acoustic BS at the predesigned frequency. Our design with functionality and
      flexibility bridges the gap between acoustic diodes and BSs and may enable novel
      multi-functional devices with great application prospects in diverse fields such
      as acoustic integrated circuits and acoustic communication.

PMID- 30206364
TI  - The regulation of miRNAs by reconstituted high-density lipoproteins in diabetes
      impaired angiogenesis.
AB  - Diabetic vascular complications are associated with impaired ischaemia-driven
      angiogenesis. We recently found that reconstituted high-density lipoproteins
      (rHDL) rescue diabetes-impaired angiogenesis. microRNAs (miRNAs) regulate
      angiogenesis and are transported within HDL to sites of injury/repair. The role
      of miRNAs in the rescue of diabetes-impaired angiogenesis by rHDL is unknown.
      Using a miRNA array, we found that rHDL inhibits hsa-miR-181c-5p expression in
      vitro and using a hsa-miR-181c-5p mimic and antimiR identify a novel anti
      angiogenic role for miR-181c-5p. miRNA expression was tracked over time post
      hindlimb ischaemic induction in diabetic mice. Early post-ischaemia when
      angiogenesis is important, rHDL suppressed hindlimb mmu-miR-181c-5p. mmu-miR-181c
      5p was not detected in the plasma or within HDL, suggesting rHDL specifically
      targets mmu-miR-181c-5p at the ischaemic site. Three known angiogenic miRNAs (mmu
      miR-223-3p, mmu-miR-27b-3p, mmu-miR-92a-3p) were elevated in the HDL fraction of
      diabetic rHDL-infused mice early post-ischaemia. This was accompanied by a
      decrease in plasma levels. Only mmu-miR-223-3p levels were elevated in the
      hindlimb 3 days post-ischaemia, indicating that rHDL regulates mmu-miR-223-3p in
      a time-dependent and site-specific manner. The early regulation of miRNAs,
      particularly miR-181c-5p, may underpin the rescue of diabetes-impaired
      angiogenesis by rHDL and has implications for the treatment of diabetes-related
      vascular complications.

PMID- 30206366
TI  - Anti-tumour activity of a first-in-class agent NUC-1031 in patients with advanced
      cancer: results of a phase I study.
AB  - BACKGROUND: Gemcitabine is used to treat a wide range of tumours, but its
      efficacy is limited by cancer cell resistance mechanisms. NUC-1031, a
      phosphoramidate modification of gemcitabine, is the first anti-cancer ProTide to
      enter the clinic and is designed to overcome these key resistance mechanisms.
      METHODS: Sixty-eight patients with advanced solid tumours who had relapsed after
      treatment with standard therapy were recruited to a dose escalation study to
      determine the recommended Phase II dose (RP2D) and assess the safety of NUC-1031.
      Pharmacokinetics and anti-tumour activity was also assessed. RESULTS: Sixty-eight
      patients received treatment, 50% of whom had prior exposure to gemcitabine. NUC
      1031 was well tolerated with the most common Grade 3/4 adverse events of
      neutropaenia, lymphopaenia and fatigue occurring in 13 patients each (19%). In 49
      response-evaluable patients, 5 (10%) achieved a partial response and 33 (67%) had
      stable disease, resulting in a 78% disease control rate. Cmax levels of the
      active intracellular metabolite, dFdCTP, were 217-times greater than those
      reported for equimolar doses of gemcitabine, with minimal toxic metabolite
      accumulation. The RP2D was determined as 825 mg/m2 on days 1, 8 and 15 of a 28
      day cycle. CONCLUSIONS: NUC-1031 was well tolerated and demonstrated clinically
      significant anti-tumour activity, even in patients with prior gemcitabine
      exposure and in cancers not traditionally perceived as gemcitabine-responsive.

PMID- 30206367
TI  - Comment on 'Neutrophils: driving progression and poor prognosis in hepatocellular
      carcinoma?'

PMID- 30206368
TI  - Reply to 'Comment on 'Circulating Neutrophils in patients with hepatocellular
      carcinoma".

PMID- 30206369
TI  - A randomised phase II trial of S-1 plus cisplatin versus vinorelbine plus
      cisplatin with concurrent thoracic radiotherapy for unresectable, locally
      advanced non-small cell lung cancer: WJOG5008L.
AB  - BACKGROUND: Cisplatin-based chemoradiotherapy is the standard treatment for
      unresectable, locally advanced non-small-cell lung cancer (NSCLC). This trial
      evaluated two experimental regimens that combine chemotherapy with concurrent
      radiotherapy. METHODS: Eligible patients with unresectable stage III NSCLC were
      randomised to either the SP arm (S-1 and cisplatin) or VP arm (vinorelbine and
      cisplatin), with early concurrent thoracic radiotherapy of 60 Gy, comprising 2 Gy
      per daily fraction. The primary endpoint was the overall survival rate at 2 years
      (2-year overall survival (OS)) (Study ID: UMIN000002420). RESULTS: From September
      2009 to September 2012, 112 patients were enroled. Of the 108 eligible patients,
      the 2-year OS was 75.6% (80% confidence interval (CI), 67-82%) in the SP arm and
      68.5% (80% CI: 60-76%) in the VP arm. The hazard ratio (HR) for death between the
      two arms was 0.85 (0.48-1.49). The median progression-free survival was 14.8
      months for the SP arm and 12.3 months for the VP arm with an HR of 0.92 (0.58
      1.44). There were four treatment-related deaths in the SP arm and five in the VP
      arm. CONCLUSIONS: The null hypotheses for 2-year OS were rejected in both arms.
      The West Japan Oncology Group will employ the SP arm as the investigational arm
      in a future phase III study.

PMID- 30206370
TI  - Carbonic anhydrase IX is a pH-stat that sets an acidic tumour extracellular pH in
      vivo.
AB  - BACKGROUND: Tumour carbonic anhydrase IX (CAIX), a hypoxia-inducible tumour
      associated cell surface enzyme, is thought to acidify the tumour microenvironment
      by hydrating CO2 to form protons and bicarbonate, but there is no definitive
      evidence for this in solid tumours in vivo. METHODS: We used 1H magnetic
      resonance spectroscopic imaging (MRSI) of the extracellular pH probe imidazolyl
      succinic acid (ISUCA) to measure and spatially map extracellular pH in HCT116
      tumours transfected to express CAIX and empty vector controls in SCID mice. We
      also measured intracellular pH in situ with 31P MRS and measured lactate in
      freeze-clamped tumours. RESULTS: CAIX-expressing tumours had 0.15 pH-unit lower
      median extracellular pH than control tumours (pH 6.71 tumour vs pH 6.86 control,
      P = 0.01). Importantly, CAIX expression imposed an upper limit for tumour
      extracellular pH at 6.93. Despite the increased lactate concentration in CAIX
      expressing tumours, 31P MRS showed no difference in intracellular pH, suggesting
      that CAIX acidifies only the tumour extracellular space. CONCLUSIONS: CAIX
      acidifies the tumour microenvironment, and also provides an extracellular pH
      control mechanism. We propose that CAIX thus acts as an extracellular pH-stat,
      maintaining an acidic tumour extracellular pH that is tolerated by cancer cells
      and favours invasion and metastasis.

PMID- 30206372
TI  - Author Correction: Nanofabrication of Conductive Metallic Structures on
      Elastomeric Materials.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 30206373
TI  - Author Correction: Treatment in myositis.
AB  - In the originally published version of this article, several references in Table
      1 were incorrect. These errors have now been corrected in the HTML and PDF
      versions of the manuscript.

PMID- 30206371
TI  - Antiviral innate immune response in non-myeloid cells is augmented by chloride
      ions via an increase in intracellular hypochlorous acid levels.
AB  - Phagocytes destroy ingested microbes by producing hypochlorous acid (HOCl) from
      chloride ions (Cl-) and hydrogen peroxide within phagolysosomes, using the enzyme
      myeloperoxidase. HOCl, the active ingredient in bleach, has
      antibacterial/antiviral properties. As myeloperoxidase is needed for HOCl
      production, non-myeloid cells are considered incapable of producing HOCl. Here,
      we show that epithelial, fibroblast and hepatic cells have enhanced antiviral
      activity in the presence of increasing concentrations of sodium chloride (NaCl).
      Replication of enveloped/non-enveloped, DNA (herpes simplex virus-1, murine
      gammaherpesvirus 68) and RNA (respiratory syncytial virus, influenza A virus,
      human coronavirus 229E, coxsackievirus B3) viruses are inhibited in a dose
      dependent manner. Whilst treatment with sodium channel inhibitors did not prevent
      NaCl-mediated virus inhibition, a chloride channel inhibitor reversed inhibition
      by NaCl, suggesting intracellular chloride is required for antiviral activity.
      Inhibition is also reversed in the presence of 4-aminobenzoic hydrazide, a
      myeloperoxidase inhibitor, suggesting epithelial cells have a peroxidase to
      convert Cl- to HOCl. A significant increase in intracellular HOCl production is
      seen early in infection. These data suggest that non-myeloid cells possess an
      innate antiviral mechanism dependent on the availability of Cl- to produce HOCl.
      Antiviral activity against a broad range of viral infections can be augmented by
      increasing availability of NaCl.

PMID- 30206374
TI  - Cell-specific epigenetic modulation.

PMID- 30206375
TI  - Junction-free Flat Copper Nanofiber Network-based Transparent Heater with High
      Transparency, High Conductivity, and High Temperature.
AB  - Transparent conducting electrodes (TCE) are widely used in a variety of
      applications including displays, light-emitting diodes (LEDS), and solar cells.
      An important factor in TCE design is active control of the sheet resistance and
      transparency; as these are inversely proportional, it is essential to develop a
      technology that can maintain high transparency, while actively controlling sheet
      resistance, for a range of applications. Here, a nanofiber network was fabricated
      based on direct electrospinning onto a three-dimensional (3-D) complex substrate;
      flat metal electrodes without junction resistance were produced using heat
      treatment and electroless deposition. The fabricated transparent electrode
      exhibited a transparency of over 90% over the entire visible light range and a
      sheet resistance of 4.9 ohms/sq. Adhesion between the electrode and substrate was
      superior to other electrospinning-based transparent electrodes. The performance
      of the transparent electrode was verified by measurements taken while using the
      electrode as a heater; a maximum temperature of 210  degrees C was achieved. The
      proposed copper nanofiber-based heater electrode offers the advantages of
      transparency as well as application to complex 3-D surfaces.

PMID- 30206378
TI  - Effect of L-citrulline supplementation on blood pressure: a systematic review and
      meta-analysis of randomized controlled trials.
AB  - The objective of this study was to systematically investigate the efficacy of
      oral L-citrulline supplementation on systolic and diastolic blood pressure.
      Studies were identified by a search of electronic databases from inception to
      April 2018, and combined and stratified analyses were used. Fifteen trials were
      identified, and data from 424 participants were included. Pooled analysis showed
      significant reductions in systolic blood pressure by -7.54 mmHg (95% confidence
      interval (CI): -9.44, -5.63; P < 0.001, I2 = 14%) and diastolic blood pressure by
      -3.77 mmHg (95% CI: -5.67, -1.86, P < 0.001, I2 = 42%) following oral
      supplementation of L-citrulline or a watermelon extract. No changes were detected
      in controls. Significant heterogeneity (I2 = 42%, P = 0.04) was found for
      diastolic blood pressure, and subgroup analysis showed significant improvements
      in systolic and diastolic blood pressure, particularly for study durations: >=6
      weeks, lower doses: <=4 g/day, and in participants with higher baseline values:
      >=130/85 mmHg. In conclusion, L-citrulline improves systolic and diastolic blood
      pressure and may be more efficacious in pre-hypertensive and hypertensive
      populations.

PMID- 30206376
TI  - Quillaja brasiliensis saponin-based nanoparticulate adjuvants are capable of
      triggering early immune responses.
AB  - Commercially available saponins are extracted from Quillaja saponaria barks,
      being Quil A(r) the most widely used. Nanoparticulate immunostimulating complexes
      (ISCOMs or ISCOMATRIX) formulated with these, are able to stimulate strong
      humoral and cellular immune responses. Recently, we formulated novel ISCOMs
      replacing QuilA(r) by QB-90 (IQB-90), a Quillaja brasiliensis leaf-extracted
      saponin fraction, and reported that IQB-90 improved antigen uptake, and induced
      systemic and mucosal antibody production, and T-cell responses. However, its
      mechanism of action remains unclear. In this study we provide a deeper insight
      into the immune stimulatory properties of QB-90 and ISCOMATRIX-like based on this
      fraction (IMXQB-90). We show herein that, when used as a viral vaccine adjuvant,
      QB-90 promotes an "immunocompetent environment". In addition, QB-90 and IMXQB-90
      induce immune-cells recruitment at draining-lymph nodes and spleen. Subsequently,
      we prove that QB-90 or IMXQB-90 stimulated dendritic cells secret IL-1beta by
      mechanisms involving Caspase-1/11 and MyD88 pathways, implying canonical
      inflammasome activation. Finally, both formulations induce a change in the
      expression of cytokines and chemokines coding genes, many of which are up
      regulated. Findings reported here provide important insights into the molecular
      and cellular mechanisms underlying the adjuvant activity of Q. brasiliensis leaf
      saponins and its respective nanoparticles.

PMID- 30206377
TI  - Targeting a phospho-STAT3-miRNAs pathway improves vesicular hepatic steatosis in
      an in vitro and in vivo model.
AB  - Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver
      disease. Although genetic predisposition and epigenetic factors contribute to the
      development of NAFLD, our understanding of the molecular mechanism involved in
      the pathogenesis of the disease is still emerging. Here we investigated a
      possible role of a microRNAs-STAT3 pathway in the induction of hepatic steatosis.
      Differentiated HepaRG cells treated with the fatty acid sodium oleate (fatty
      dHepaRG) recapitulated features of liver vesicular steatosis and activated a cell
      autonomous inflammatory response, inducing STAT3-Tyrosine-phosphorylation. With a
      genome-wide approach (Chromatin Immunoprecipitation Sequencing), many phospho
      STAT3 binding sites were identified in fatty dHepaRG cells and several STAT3
      and/or NAFLD-regulated microRNAs showed increased expression levels, including
      miR-21. Innovative CARS (Coherent Anti-Stokes Raman Scattering) microscopy
      revealed that chemical inhibition of STAT3 activity decreased lipid accumulation
      and deregulated STAT3-responsive microRNAs, including miR-21, in lipid overloaded
      dHepaRG cells. We were able to show in vivo that reducing phospho-STAT3-miR-21
      levels in C57/BL6 mice liver, by long-term treatment with metformin, protected
      mice from aging-dependent hepatic vesicular steatosis. Our results identified a
      microRNAs-phosphoSTAT3 pathway involved in the development of hepatic steatosis,
      which may represent a molecular marker for both diagnosis and therapeutic
      targeting.

PMID- 30206379
TI  - Fluorescently Labelled Silica Coated Gold Nanoparticles as Fiducial Markers for
      Correlative Light and Electron Microscopy.
AB  - In this work, gold nanoparticles coated with a fluorescently labelled (rhodamine
      B) silica shell are presented as fiducial markers for correlative light and
      electron microscopy (CLEM). The synthesis of the particles is optimized to obtain
      homogeneous, spherical core-shell particles of arbitrary size. Next, particles
      labelled with different fluorophore densities are characterized to determine
      under which conditions bright and (photo)stable particles can be obtained. 2 and
      3D CLEM examples are presented where optimized particles are used for
      correlation. In the 2D example, fiducials are added to a cryosection of cells
      whereas in the 3D example cells are imaged after endocytosis of the fiducials.
      Both examples demonstrate that the particles are clearly visible in both
      modalities and can be used for correlation. Additionally, the recognizable core
      shell structure of the fiducials proves to be very powerful in electron
      microscopy: it makes it possible to irrefutably identify the particles and makes
      it easy to accurately determine the center of the fiducials.

PMID- 30206381
TI  - Mechanisms of leptin resistance revealed.

PMID- 30206382
TI  - RANKL reverse signalling and bone.

PMID- 30206380
TI  - Population level mitogenomics of long-lived bats reveals dynamic heteroplasmy and
      challenges the Free Radical Theory of Ageing.
AB  - Bats are the only mammals capable of true, powered flight, which drives an
      extremely high metabolic rate. The "Free Radical Theory of Ageing" (FTRA) posits
      that a high metabolic rate causes mitochondrial heteroplasmy and the progressive
      ageing phenotype. Contrary to this, bats are the longest-lived order of mammals
      given their small size and high metabolic rate. To investigate if bats exhibit
      increased mitochondrial heteroplasmy with age, we performed targeted, deep
      sequencing of mitogenomes and measured point heteroplasmy in wild, long lived
      Myotis myotis. Blood was sampled from 195 individuals, aged between <1 and at 6+
      years old, and whole mitochondria deep-sequenced, with a subset sampled over
      multiple years. The majority of heteroplasmies were at a low frequency and were
      transitions. Oxidative mutations were present in only a small number of
      individuals, suggesting local oxidative stress events. Cohort data showed no
      significant increase in heteroplasmy with age, while longitudinal data from
      recaptured individuals showed heteroplasmy is dynamic, and does not increase
      uniformly over time. We show that bats do not suffer from the predicted,
      inevitable increase in heteroplasmy as posited by the FRTA, instead heteroplasmy
      was found to be dynamic, questioning its presumed role as a primary driver of
      ageing.

PMID- 30206383
TI  - Shared variants for osteoporosis and T2DM.

PMID- 30206384
TI  - Gene therapy for neurological disorders: progress and prospects.
AB  - This corrects the article DOI: 10.1038/nrd.2018.110.

PMID- 30206385
TI  - Defining orphan conditions in the context of the European orphan regulation:
      challenges and evolution.
AB  - The definition and acceptability of an orphan condition is pivotal for the
      assessment of European orphan medicinal product designation applications, and
      consequently the eligibility for incentives. Here, based on the experiences of
      the Committee for Orphan Medicinal Products, we discuss how to define orphan
      conditions in the context of the European regulatory framework.

PMID- 30206387
TI  - Skin bacterium learns to shrug off antibiotic of last resort.

PMID- 30206388
TI  - India's surprise plan to send people to space by 2022.

PMID- 30206386
TI  - Phylogenetic evidence for independent origins of GDF1 and GDF3 genes in anurans
      and mammals.
AB  - Growth differentiation factors 1 (GDF1) and 3 (GDF3) are members of the
      transforming growth factor superfamily (TGF-beta) that is involved in fundamental
      early-developmental processes that are conserved across vertebrates. The
      evolutionary history of these genes is still under debate due to ambiguous
      definitions of homologous relationships among vertebrates. Thus, the goal of this
      study was to unravel the evolution of the GDF1 and GDF3 genes of vertebrates,
      emphasizing the understanding of homologous relationships and their evolutionary
      origin. Our results revealed that the GDF1 and GDF3 genes found in anurans and
      mammals are the products of independent duplication events of an ancestral gene
      in the ancestor of each of these lineages. The main implication of this result is
      that the GDF1 and GDF3 genes of anurans and mammals are not 1:1 orthologs. In
      other words, genes that participate in fundamental processes during early
      development have been reinvented two independent times during the evolutionary
      history of tetrapods.

PMID- 30206389
TI  - The world's first flexitarian shark grazes like a cow.

PMID- 30206391
TI  - Pulsar discoverer Jocelyn Bell Burnell wins $3-million Breakthrough Prize.

PMID- 30206390
TI  - Google unveils search engine for open data.

PMID- 30206392
TI  - South Africa pushes science to improve daily life.

PMID- 30206393
TI  - The stars that team up to push planets to their death.

PMID- 30206394
TI  - Meagre ranks of anti-flu drugs look set to grow.

PMID- 30206395
TI  - 'Molecular sieve' offers inexpensive way to sift plastic's raw materials.

PMID- 30206396
TI  - How to warn of a pulsating artery that could burst any time.

PMID- 30206397
TI  - Raging wildfires send scientists scrambling to study health effects.

PMID- 30206398
TI  - C aches of mummified penguins warn of climate-change impacts.

PMID- 30206399
TI  - The long entanglement of war and astrophysics.

PMID- 30206400
TI  - The last polymath.

PMID- 30206401
TI  - A fieldwork flop needn't be a disaster.

PMID- 30206402
TI  - Post-crash economics: have we learnt nothing?

PMID- 30206403
TI  - Pakistan's prosperity needs independent experts.

PMID- 30206404
TI  - Exploration of serum sensitive biomarkers of fatty liver in dairy cows.
AB  - Serum proteins are sensitive with diseases in dairy cows, and some of them could
      be used as biomarkers for fatty liver. This study aimed to explore serum
      biomarkers for fatty liver in dairy cows. A total of 28 early lactating dairy
      cows were chosen from a commercial dairy herds, liver samples were collected for
      determining concentration of triacylglycerol (TAG), and serum samples were
      collected for measuring fibroblast growth factor-21 (FGF-21), adiponectin,
      Lipoprotein-associated phospholipase A2 (LP-PLA2), and hemoglobin (Hb). Dairy
      cows were divided into fatty liver (liver TAG > 5%, wet weight) and control group
      (liver TAG < 5%, wet weight). Concentration of FGF-21 was greater in fatty liver
      cows, while the concentration of LP-PLA2 and Hb was less. The concentration of
      FGF-21 and total Hb had strong correlation with the liver TAG as well as good
      prediction power (kappa value = 0.79 and 0.58, respectively). These results
      suggested that the serum concentration of FGF-21 and total Hb could be
      potentially used as fatty liver biomarkers in lactating dairy cows.

PMID- 30206405
TI  - Accretionary prism collapse: a new hypothesis on the source of the 1771 giant
      tsunami in the Ryukyu Arc, SW Japan.
AB  - The giant 1771 Yaeyama tsunami occurred in the southwestern part of the Ryukyu
      Arc, a region on an obliquely subducting plate boundary, which shows no direct
      evidence of inter-plate coupling. Studies of tsunami boulders and deposits
      suggest that the recurrence interval of comparably giant tsunamis is roughly 500
      to 1000 years. Tsunami source models, which include either slip on a shallow
      plate boundary or active faulting plus a landslide on the overriding plate, are
      controversial because of inconsistencies in the geophysical and geological data.
      We discovered a seafloor depression that is approximately 30 km wide and 80 km
      long extending in the ESE-WNW direction. This depression is accompanied by a
      seaward bulge on the accretionary prism along the Ryukyu Trench, which is based
      on detailed bathymetric data and interpreted to be the result of accretionary
      prism collapse and seaward displacement by rotational slide. A simple tsunami
      simulation shows that the slide is a plausible source of the 1771 tsunami. We
      propose a collapse model, in which the accretionary prism remained over-steepened
      as strike-slip faulting removed the prism toe. Our model indicates that some
      oblique subduction zones are capable of generating giant tsunamis regardless of
      weak or strong coupling.

PMID- 30206406
TI  - Adenocarcinoma within anorectal fistulae: different clinicopathological
      characteristics between Crohn's disease-associated type and the usual type.
AB  - Adenocarcinoma within anorectal fistulae is rare and is sometimes associated with
      Crohn's disease. Crohn's disease-associated adenocarcinoma within anorectal
      fistulae has a poor prognosis; however, little is known about the
      clinicopathological differences between Crohn's disease-associated adenocarcinoma
      within anorectal fistulae and usual adenocarcinoma within anorectal fistulae. We
      retrospectively searched patients' charts and pathology archives at Tokyo Yamate
      Medical Center and Tokyo Medical and Dental University Hospital for
      adenocarcinoma within anorectal fistulae. Clinical and pathological data were
      collected and immunohistochemical examinations were conducted. Overall survival
      rate was estimated using the Kaplan-Meier method. Prognostic factors of overall
      survival were assessed using univariate and multivariate Cox regression analyses.
      We examined 82 cases of adenocarcinoma within anorectal fistulae. Fifty-nine of
      82 cases (72%) had usual adenocarcinoma within anorectal fistulae, while the
      remaining 23 cases (28%) had Crohn's disease-associated adenocarcinoma within
      anorectal fistulae. Patients with Crohn's disease-associated adenocarcinoma
      within anorectal fistulae were diagnosed at a younger age and at a more advanced
      stage than those with usual adenocarcinoma within anorectal fistulae. Macroscopic
      and histological types were also different between usual adenocarcinoma within
      anorectal fistulae and Crohn's disease-associated adenocarcinoma within anorectal
      fistulae. Crohn's disease-associated adenocarcinoma within anorectal fistulae
      included more ulcerative types and high-grade adenocarcinomas. The rate of
      lymphovascular invasion was higher in Crohn's disease-associated adenocarcinoma
      within anorectal fistulae. Immunohistochemically, the expression of E-cadherin,
      p53, and MUC5AC differed between usual adenocarcinoma within anorectal fistulae
      and Crohn's disease-associated adenocarcinoma within anorectal fistulae. Patients
      with Crohn's disease-associated adenocarcinoma within anorectal fistulae
      exhibited worse overall survival than those with usual adenocarcinoma within
      anorectal fistulae, and vascular invasion was the strongest significant
      independent predictor of overall survival in patients with adenocarcinoma within
      anorectal fistulae. In conclusion, usual adenocarcinoma within anorectal fistulae
      and Crohn's disease-associated adenocarcinoma within anorectal fistulae have
      different clinicopathological characteristics and should be considered separate
      clinical entities.

PMID- 30206407
TI  - Targeted next-generation sequencing in the detection of mismatch repair
      deficiency in endometrial cancers.
AB  - Mismatch repair deficiency represents a biomarker of immunotherapy response and a
      phenotypic feature of Lynch syndrome-associated endometrial cancers. Using a
      targeted next-generation sequencing assay, we identified molecular features of
      mismatch repair deficiency, specifically insertion and deletion mutations in
      mononucleotide repeats, and established thresholds for the number of such
      mutations to classify endometrial cancers as mismatch repair deficient,
      proficient, or indeterminate. Sequencing classification was compared to the loss
      of MLH1, MSH2, MSH6, or PMS2 expression by immunohistochemistry. A total of 259
      endometrial cancers were classified by sequencing as mismatch repair deficient (n
      = 48, 19%), proficient (n = 199, 77%), or indeterminate (n = 12, 5%). Sequencing
      findings were concordant with loss of expression of at least one mismatch repair
      protein in 47 of 48 (98%) cases classified as deficient and retained expression
      of all four proteins in 190 of 199 (95%) cases classified as proficient. Of the
      12 cases classified as indeterminate, 7 (58%) demonstrated mismatch repair
      protein loss. Overall, targeted next-generation sequencing exhibited a high rate
      of concordance with immunohistochemistry for mismatch repair deficiency; however,
      sequencing was indeterminate in a few cases and demonstrated a false negative
      rate of 5%. Although we recommend implementation of a mismatch repair deficiency
      algorithm for laboratories performing next-generation sequencing cancer panels,
      immunohistochemistry remains a cost-effective screening method for mismatch
      repair deficiency in endometrial cancer.

PMID- 30206408
TI  - Phosphaturic mesenchymal tumor with an admixture of epithelial and mesenchymal
      elements in the jaws: clinicopathological and immunohistochemical analysis of 22
      cases with literature review.
AB  - Information on the heterogeneity of phosphaturic mesenchymal tumor, a rare entity
      associated with tumor-induced osteomalacia, is limited. In this retrospective
      analysis of 222 phosphaturic mesenchymal tumors, 22 cases exhibited mixed
      mesenchymal and epithelial elements, which we propose to term "phosphaturic
      mesenchymal tumor, mixed epithelial, and connective tissue type." Phosphaturic
      mesenchymal tumor of the mixed epithelial and connective tissue type showed a
      distinctive and significant male predominance (male:female = 2.67:1), with most
      patients diagnosed at <40 years old. Moreover, all tumors were mainly located in
      the alveolar bone with focal invasion into surrounding soft tissue and oral
      mucosa, which could be detected preoperatively by oral examination. The
      mesenchymal component, composed of spindled cells resembling fibroblasts or
      myofibroblasts arranged in a storiform or fascicular pattern, exhibited a less
      prominent vasculature and lower cellularity than the typical phosphaturic
      mesenchymal tumor (mixed connective tissue type). The epithelial component was
      typically haphazardly and diffusely distributed throughout the tumor, forming
      small, irregular nests resembling odontogenic epithelial nests. All cases were
      immunoreactive for fibroblast growth factor-23, somatostatin receptor 2A, and NSE
      in both components. Mostly also demonstrated positive staining for CD99 (21/22,
      96%), CD56 (16/22, 73%), Bcl-2 (21/22, 96%), and D2-40 (19/22, 86%) in one or
      both components. S100 was positive in both components in one of seven cases.
      Interestingly, immunoreactivity was typically stronger and more diffuse in the
      epithelial than in the paired mesenchymal components. The mesenchymal component
      was also diffusely positive for CD68 (17/17, 100%) and showed variable focal
      staining for SMA (15/22, 68%) and CD34 (9/19, 47 %). These results indicate that
      phosphaturic mesenchymal tumor of the mixed epithelial and connective tissue type
      has distinctive clinicopathological characteristics and a polyimmunophenotypic
      profile.

PMID- 30206409
TI  - Malignant Tenosynovial Giant Cell Tumor: The True "Synovial Sarcoma?" A
      Clinicopathologic, Immunohistochemical, and Molecular Cytogenetic Study of 10
      Cases, Supporting Origin from Synoviocytes.
AB  - We present our experience with ten well-characterized malignant tenosynovial
      giant cell tumors, including detailed immunohistochemical analysis of all cases
      and molecular cytogenetic study for CSF1 rearrangement in a subset. Cases
      occurred in 7 M and 3 F (mean age: 52 years; range: 26-72 years), and involved
      the ankle/foot (n = 1), finger/toe (n = 3), wrist (n = 1), pelvic region (n = 3),
      leg (n = 1), and thigh (n = 1). There were eight primary and two secondary
      malignant tenosynovial giant cell tumors. Histologically, all cases showed
      definite areas of typical tenosynovial giant cell tumor. The malignant areas
      varied in appearance. In some cases, isolated malignant-appearing large
      mononuclear cells with high nuclear grade and mitotic activity were identified
      within otherwise-typical tenosynovial giant cell tumor, as well as forming larger
      masses of similar-appearing malignant cells. Occasionally, these nodules of
      malignant large mononuclear cells showed transition to pleomorphic spindle cell
      sarcoma, with varying degrees of collagenization and myxoid change. One malignant
      tenosynovial giant cell tumor was composed of sheets of monotonous large
      mononuclear cells with high nuclear grade, growing in a hyalinized, osteoid-like
      matrix, with areas of heterologous osteocartilaginous differentiation. Mitotic
      activity ranged from 2 to 34 mitoses per 10 HPF (mean 18/10 HPF). Geographic
      necrosis was observed in four cases. The malignant-appearing large mononuclear
      cells were consistently positive for clusterin and negative for CD163, CD68, and
      CD11c. Desmin was positive in a small minority of these cells. Areas in malignant
      tenosynovial giant cell tumor resembling pleomorphic spindle cell sarcoma or
      osteo/chondrosarcoma showed loss of clusterin expression. RANKL
      immunohistochemistry was positive in the large mononuclear cells in eight cases.
      Two cases showed an unbalanced rearrangement of the CSF1 locus. Follow-up (nine
      patients; range 0.5-66 months; mean 20 months) showed three patients dead of
      disease, with three other living patients having lung and lymph node metastases;
      three patients were disease-free. We conclude that malignant tenosynovial giant
      cell tumors are highly aggressive sarcomas with significant potential for locally
      destructive growth, distant metastases, and death from disease. The morphologic
      and immunohistochemical features of these tumors and the presence of CSF1
      rearrangements support origin of malignant tenosynovial giant cell tumor from
      synoviocytes.

PMID- 30206410
TI  - Low miR200c expression in tumor budding of invasive front predicts worse survival
      in patients with localized colon cancer and is related to PD-L1 overexpression.
AB  - At the histological level, tumor budding in colon cancer is the result of cells
      undergoing at least partial epithelial-to-mesenchymal transition. The microRNA
      200 family is an important epigenetic driver of this process, mainly by
      downregulating zinc-finger E-box binding homeobox (ZEB) and transforming growth
      factor beta (TGF-beta) expression. We retrospectively explored the expression of
      the miR200 family, and ZEB1 and ZEB2, and their relationship with immune
      resistance mediated through PD-L1 overexpression. For this purpose, we analyzed a
      series of 125 colon cancer cases and took samples from two different tumor sites:
      the area of tumor budding at the invasive front and from the tumor center. We
      found significant ZEB overexpression and a reduction in miR200 in budding areas,
      a profile compatible with epithelial-to-mesenchymal transition. In multivariate
      analysis of the cases with localized disease, low miR200c expression in budding
      areas, but not at the tumor center, was an adverse tumor-specific survival factor
      (hazard ratio: 0.12; 95% confidence interval: 0.03-0.81; p = 0.02) independent of
      the clinical stage of the disease. PD-L1 was significantly overexpressed in the
      budding areas and its levels correlated with a mesenchymal transition profile.
      These results highlight the importance of including budding areas among the
      samples used for biomarker evaluation and provides relevant data on the influence
      of mesenchymal transition in the immune resistance mediated by PD-L1
      overexpression.

PMID- 30206411
TI  - The role of a monoclonal antibody 11C8B1 as a diagnostic marker of IDH2-mutated
      sinonasal undifferentiated carcinoma.
AB  - IDH2 R172 mutations occur in >80% sinonasal undifferentiated carcinomas ("SNUC")
      and ~80% of these are R172S and R172T variants. We examined the utility of the
      monoclonal antibody 11C8B1 to IDH2 R172S in IDH2 R172-mutated tumors to establish
      an immunohistochemistry protocol as a surrogate method for IDH2 R172S mutation
      detection. Eighty-eight formalin-fixed paraffin-embedded tumors including 42
      sinonasal tumors and a variety of IDH1/2-mutated malignancies were tested by
      immunohistochemistry. The IDH1/2 mutation status was determined in 86 cases by a
      targeted massively parallel sequencing MSK-IMPACTTM assay. Interestingly,
      monoclonal antibody 11C8B1 was reactive with all IDH2 R172S (N = 15) mutated
      tumors including 12 sinonasal carcinomas, 2 high-grade sarcomas and one
      intrahepatic cholangiocarcinoma, and with all R172T (N = 3) mutated sinonasal
      carcinomas displaying a distinct granular cytoplasmic labeling in all R172S/T
      mutated malignancies. 11C8B1 immunohistochemistry was also positive in 2 of 6
      IDH1 R132S-mutated tumors, including one intrahepatic cholangiocarcinoma and one
      chondrosarcoma showing a smooth homogeneous cytoplasmic staining pattern. All
      IDH2 R172G/K/M/W (N = 22) and IDH1 132H/C/G/L (N = 15) mutated tumors, and all
      IDH1/2-wild-type tumors (N = 25), including a histologic variety of 23 sinonasal
      tumors, were immunonegative. Importantly, 11 sinonasal undifferentiated
      carcinomas (N = 14, 79%) and 3 (100%) high-grade neuroendocrine carcinomas, large
      cell type were 11C8B1 immunopositive. Literature search revealed a virtual
      absence of IDH2 R172 and IDH1 R132S mutations in >1000 cases of 8 different
      malignancies included in the differential diagnosis of sinonasal undifferentiated
      carcinoma. Our study suggests that positive IDH2 11C8B1 immunohistochemistry in
      sinonasal carcinomas would be highly predictive of the presence of IDH2 R172S/T
      mutations and could serve as a reliable adjunct diagnostic marker of sinonasal
      undifferentiated carcinomas in >70% cases.

PMID- 30206412
TI  - VEGFA amplification/increased gene copy number and VEGFA mRNA expression in renal
      cell carcinoma with TFEB gene alterations.
AB  - Amplification of vascular endothelial growth factor A (VEGFA) has been recently
      reported in TFEB-amplified renal cell carcinomas regardless the level of TFEB
      amplification. We sought to determine VEGFA amplification by fluorescent in situ
      hybridization (FISH) and VEGFA mRNA expression by in situ hybridization (RNAscope
      2.5) in a series of 10 renal cell carcinomas with TFEB gene alterations, either
      amplification and/or rearrangement (t(6;11) renal cell carcinoma). TFEB gene
      rearrangement was demonstrated in eight cases, whereas the remaining two cases
      showed a high level of TFEB (> 10 copies of fluorescent signals) gene
      amplification without evidence of rearrangement. Among the eight t(6;11) renal
      cell carcinomas (TFEB-rearranged cases), one case displayed a high level of TFEB
      gene amplification and two showed increased TFEB gene copy number (3-4 copies of
      fluorescent signals). Those three cases behaved aggressively. By FISH, VEGFA was
      amplified in all three cases with TFEB amplification and increased VEGFA gene
      copy number was observed in the two aggressive cases t(6;11) renal cell
      carcinomas with an overlapping increased number of TFEB fluorescent signals.
      Overall, VEGFA mRNA expression was observed in 8 of 10 cases (80%); of these 8
      cases, 3 cases showed high-level TFEB amplification, one case showed TFEB
      rearrangement with increased TFEB gene copy number, whereas four showed TFEB gene
      rearrangement without increased copy number. In summary, VEGFA
      amplification/increased gene copy number and VEGFA mRNA expression occur in TFEB
      amplified renal cell carcinoma, but also in a subset of t(6;11) renal cell
      carcinoma demonstrating aggressive behavior, and in unamplified conventional
      t(6;11) renal cell carcinoma suggesting VEGFA as potential therapeutic target in
      these neoplasms even in the absence of TFEB amplification. We finally propose
      that all the renal tumors showing morphological characteristics suggesting
      t(6;11) renal cell carcinoma and all unclassified renal cell carcinomas, either
      high grade or low grade, should immunohistochemically be evaluated for cathepsin
      K and/or Melan-A and if one of them is positive, tested for TFEB gene alteration
      and VEGFA gene amplification.

PMID- 30206413
TI  - Genetic and molecular reappraisal of spindle cell adamantinoma of bone reveals a
      small subset of misclassified intraosseous synovial sarcoma.
AB  - Adamantinoma represents a distinct group of bone tumors showing both mesenchymal
      and epithelial differentiation most commonly involving the tibial diaphysis. Most
      adamantinomas contain a fibro-osseous component and an epithelial component
      consisting of squamous or basaloid cells. Adamantinomas are considered malignant
      neoplasms requiring en bloc excision that frequently recur locally and can rarely
      metastasize. Rare adamantinomas show an epithelial component consisting
      predominantly of monomorphic spindle cells, which, combined with an epithelial
      immunophenotype, can mimic monophasic synovial sarcoma. Synovial sarcoma is very
      rare in bone. It is considered a high-grade sarcoma that typically necessitates
      chemotherapy. However, the relationship between spindle cell adamantinoma and
      intraosseous synovial sarcoma has not been investigated. The current study was
      prompted by identification of a presumed spindle cell adamantinoma of the tibia
      with diffuse keratin expression that harbored a SS18 gene region rearrangement.
      FISH of eight additional bone tumors initially classified as spindle cell
      adamantinoma based on clinicoradiopathologic findings revealed one additional
      case with SS18 rearrangement. Histologically, both intraosseous synovial sarcoma
      and spindle cell adamantinoma demonstrated uniform fusiform nuclei with scant
      cytoplasm, short fascicles and low mitotic activity. The adamantinomas, but not
      the synovial sarcomas, were more likely to show overt epithelial differentiation
      in the form of pseudoglands or squamous nests. Immunohistochemistry of all cases,
      irrespective of SS18 status, showed diffuse keratin positivity in the spindle
      cell component, and less consistent EMA positivity. Clinical follow-up was
      available in both intraosseous synovial sarcomas, one of which recurred and the
      other metastasized. Two of the six spindle cell adamantinomas with follow-up
      metastasized. The above findings highlight the morphologic and immunophenotypic
      overlap between spindle cell adamantinoma and intraosseous synovial sarcoma of
      the tibia. Investigation of SS18 status to exclude synovial sarcoma is suggested
      prior to rendering a diagnosis of spindle cell adamantinoma.

PMID- 30206414
TI  - Breast implant-associated anaplastic large cell lymphoma: a review.
AB  - Breast implant-associated anaplastic large cell lymphoma is a newly recognized
      provisional entity in the 2017 revision of the World Health Organization
      Classification of Tumors of Hematopoietic and Lymphoid Tissues. It is an
      uncommon, slow growing T-cell lymphoma with morphology and immunophenotype
      similar to anaplastic lymphoma kinase-negative anaplastic large cell lymphoma.
      However, the presentation and treatment are unique. Breast implant-associated
      anaplastic large cell lymphoma often presents as a unilateral effusion confined
      to the capsule of a textured-surface breast implant, a median time of 9 years
      after the initial implants have been placed. Although it follows an indolent
      clinical course, breast implant-associated anaplastic large cell lymphoma has the
      potential to form a mass, to invade locally through the capsule into breast
      parenchyma or soft tissue and/or to spread to regional lymph nodes. In most
      cases, an explantation with a complete capsulectomy removing all disease, without
      chemotherapy is considered to be curative and confers an excellent event free and
      overall survival. Here we provide a comprehensive review of breast implant
      associated anaplastic large cell lymphoma, including history, epidemiology,
      clinical features, imaging and pathology findings, pathologic handling,
      pathogenic mechanisms, model for progression, therapy and outcomes as well as an
      analysis of causality between breast implants and anaplastic large cell lymphoma.

PMID- 30206415
TI  - Transcriptional analysis distinguishes breast implant-associated anaplastic large
      cell lymphoma from other peripheral T-cell lymphomas.
AB  - Breast implant-associated anaplastic large cell lymphoma is a new provisional
      entity in the revised World Health Organization classification of lymphoid
      malignancies, the pathogenesis and cell of origin of which are still unknown. We
      performed gene expression profiling of microdissected breast implant-associated
      anaplastic large cell lymphoma samples and compared their transcriptional
      profiles with those previously obtained from normal T-cells and other peripheral
      T-cell lymphomas and validated expression of selected markers by
      immunohistochemistry. Our results indicate that most breast implant-associated
      anaplastic large cell lymphomas exhibit an activated CD4+ memory T-cell
      phenotype, which is associated with CD25 and FoxP3 expression. Gene ontology
      analyses revealed upregulation of genes involved in cell motility programs (e.g.,
      CCR6, MET, HGF, CXCL14) in breast implant-associated anaplastic large cell
      lymphomas compared to normal CD4+ T-cells and upregulation of genes involved in
      myeloid cell differentiation (e.g., PPARg, JAK2, SPI-1, GAB2) and viral gene
      transcription (e.g., RPS10, RPL17, RPS29, RPL18A) compared to other types of
      peripheral T-cell lymphomas. Gene set enrichment analyses also revealed shared
      features between the molecular profiles of breast implant-associated anaplastic
      large cell lymphomas and other types of anaplastic large cell lymphomas,
      including downregulation of T-cell receptor signaling and STAT3 activation. Our
      findings provide novel insights into the biology of this rare disease and further
      evidence that breast implant-associated anaplastic large cell lymphoma represents
      a distinct peripheral T-cell lymphoma entity.

PMID- 30206416
TI  - Identifying the predictors of needling after XEN gel implant.
AB  - PURPOSE: To identify factors associated with probability of needling after XEN
      implant. METHODS: Analysis of data from prospective case series of patients with
      standalone XEN implant or combined XEN + cataract. Primary outcome was to
      determine whether postoperative day 1 and week 1 intraocular pressure (IOP), type
      of glaucoma, and glaucoma severity affected probability and number of needling
      interventions required. RESULTS: A total of 149 eyes of 113 patients were
      included in the analysis. In the XEN alone group, mean IOP at day 1 and week 1
      was 9.70 +/- 5.43 and 10.33 +/- 4.41 mmHg, respectively. Eyes with lower IOP on
      day 1 were less likely to require needling (Odds ratio; OR, 1.14; 95% CI, 1.02
      1.28; p = 0.02). A similar association (OR, 1.15; 95% CI, 1.06-1.26; p = 0.001)
      was observed between day 1 IOP in and number of needling interventions. In the
      XEN + cataract group, mean IOPs at day 1 and week 1 were 13.75 +/- 7.52 and 11.81
      +/- 5.36 mmHg, respectively. No significant association was noted between early
      postoperative IOP and probability or number of needling in this group. With IOP >
      20 mmHg the probability of needling was ~ 80%. This number decreased to 35% if
      day 1 IOP was < 10 mmHg. CONCLUSION: Postoperative day 1 IOP is a predictor for
      needling in patients undergoing standalone XEN implantation. These results
      suggest that surgeons should not wait too long to intervene via needling if IOP
      in the early postoperative period is in the high teens or above. Type or severity
      of glaucoma did not influence the probability of needling or number of needling
      interventions required.

PMID- 30206417
TI  - Computer analysis of individual cataract surgery segments in the operating room.
AB  - PURPOSE: Objective feedback is important for the continuous development of
      surgical skills. Motion tracking, which has previously been validated across an
      entire cataract procedure, can be a useful adjunct. We aimed to measure
      quantitative differences between junior and senior surgeons' performance in three
      distinct segments. We further explored whether automated analysis of trainee
      surgical videos through PhacoTracking could be aligned with metrics from the
      EyeSi virtual reality simulator, allowing focused improvement of these areas in a
      controlled environment. METHODS: Prospective cohort analysis, comparing junior
      vs. senior surgeons' real-life performance in distinct segments of cataract
      surgery: continuous curvilinear capsulorhexis (CCC), phacoemulsification, and
      irrigation and aspiration (I&A). EyeSi metrics that could be aligned with motion
      tracking parameters were identified. Motion tracking parameters (instrument path
      length, number of movements and total time) were measured. t-test used between
      the two cohorts for each component to check for any significance (p < 0.05).
      RESULTS: A total of 120 segments from videos of 20 junior and 20 senior surgeons
      were analysed. Significant differences between junior and senior surgeons were
      found during CCC (path length p = 0.0004; number of movements p < 0.0001; time
      taken p < 0.0001), phacoemulsification (path length p < 0.0001; number of
      movements p < 0.0001; time taken p < 0.0001), and irrigation and aspiration (path
      length p = 0.006; number of movements p = 0.013; time taken p = 0.036).
      CONCLUSION: Individual segments of cataract surgery analysed using motion
      tracking appear to discriminate between junior and senior surgeons. Alignment of
      motion tracking and EyeSi parameters could enable independent, task specific,
      objective and quantitative feedback for each segment of surgery thus mirroring
      the widely utilised modular training.

PMID- 30206418
TI  - Quantitative automated circumpapillary microvascular density measurements: a new
      angioOCT-based methodology.
AB  - PURPOSE: To develop a new methodology to detect glaucoma damage based on
      circumpapillary microvascular density (cpmVD) as measured by optical coherence
      tomography angiography (angioOCT). METHODS: AngioOCT scans from a random eye of
      40 healthy subjects (aged 63 +/- 14 years) and 82 glaucoma patients (aged 66 +/-
      9 years with an average visual field loss of -7.8 +/- 6.5 dB) were used to
      develop a new angioOCT evaluation methodology. Optic disc-centred 3 * 3 mm images
      were collected (Angioplex(r), Zeiss Cirrus 5000 HD-OCT). An annular area with an
      inner radius of 1.16 mm and outer radius of 1.44 mm was chosen as the region of
      interest (ROI), with cpmVD calculated through lower envelope modulation avoiding
      the influence of the major retinal vessels. Additionally, the cpmVD and the
      microvascular density (mVD), stratified by sectors, were compared with the
      respective retinal nerve fibre layer (RNFL) thickness. RESULTS: A significantly
      lower cpmVD was observed in the glaucoma group, for all visual field sectors (p <
      0.001), when comparing to the healthy group. The inferior and superior mVD
      sectors showed the largest differences between groups. Moreover, glaucoma was
      linked to a reduction of cpmVD variation when compared to the healthy group.
      Lastly, a comparison between two healthy subgroups showed that the method is not
      biased by the presence of slight movement artefacts, optic disc dimensions and
      vessel crowding (p > 0.05). CONCLUSIONS: The presented open-source methodology
      provides a robust quantitative analysis of the 360 mVD. It shows that cpmVD, and
      mVD sectors measured by angioOCT, can be used in everyday glaucoma practice.

PMID- 30206419
TI  - Novel models of drug relapse and craving after voluntary abstinence.

PMID- 30206420
TI  - Amyloid oligomer interactions and polymorphisms: disease-relevant distinct
      assembly of alpha-synuclein and tau.

PMID- 30206423
TI  - Clinical efficacy of upper limb robotic therapy in people with tetraplegia: a
      pilot randomized controlled trial.
AB  - STUDY DESIGN: A pilot randomized controlled trial. OBJECTIVES: To evaluate the
      clinical efficacy of upper limb robotic therapy in people with tetraplegia.
      SETTING: Inpatient rehabilitation hospital in Seoul, Korea. METHODS: Participants
      were randomly allocated to a robotic therapy (RT) or occupational therapy (OT)
      group. Both groups received usual care plus 30 min of additional therapy per day
      for 4 weeks. The additional therapy provided to the OT group was OT, and the
      additional therapy provided to RT group was RT using the Armeo Power. Primary
      outcomes were the Medical Research Council scale of each key muscle and Upper
      Extremity Motor Score (UEMS) for the trained arm. Secondary outcomes were the
      Spinal Cord Independence Measurement version III (SCIM-III) subscale and total
      score. Evaluations were performed at baseline and 4 weeks. RESULTS: A total of 34
      individuals with tetraplegia were included; 17 in each group. At 4 weeks, the
      median (IQR) change in UEMS in the RT group was 1/25 (0 to 3) points compared
      with 0/25 (-1 to 1) points in the OT group (p = 0.03). The median (IQR) change in
      total SCIM-III score in the RT group was 7/100 (1.5 to 11) points compared with
      0/100 (-8 to 4) points in the OT group (p < 0.01). CONCLUSIONS: There were small
      improvements in motor strength and SCIM-III scores in the RT group, but there
      were no statistically significant differences between the groups. Further studies
      are required for a better understanding of the effects of RT for people with
      tetraplegia.

PMID- 30206422
TI  - Anti-TNFR1 targeting in humanized mice ameliorates disease in a model of multiple
      sclerosis.
AB  - Tumour necrosis factor (TNF) signalling is mediated via two receptors, TNF
      receptor 1 (TNFR1) and TNF-receptor 2 (TNFR2), which work antithetically to
      balance CNS immune responses involved in autoimmune diseases such as multiple
      sclerosis. To determine the therapeutic potential of selectively inhibiting TNFR1
      in mice with experimental autoimmune encephalomyelitis, we used chimeric
      human/mouse TNFR1 knock-in mice allowing the evaluation of antagonistic anti
      human TNFR1 antibody efficacy. Treatment of mice after onset of disease with
      ATROSAB resulted in a robust amelioration of disease severity, correlating with
      reduced central nervous system immune cell infiltration. Long-term efficacy of
      treatment was achieved by treatment with the parental mouse anti-human TNFR1
      antibody, H398, and extended by subsequent re-treatment of mice following
      relapse. Our data support the hypothesis that anti-TNFR1 therapy restricts immune
      cell infiltration across the blood-brain barrier through the down-regulation of
      TNF-induced adhesion molecules, rather than altering immune cell composition or
      activity. Collectively, we demonstrate the potential for anti-human TNFR1
      therapies to effectively modulate immune responses in autoimmune disease.

PMID- 30206424
TI  - Deltaproteobacteria (Pelobacter) and Methanococcoides are responsible for choline
      dependent methanogenesis in a coastal saltmarsh sediment.
AB  - Coastal saltmarsh sediments represent an important source of natural methane
      emissions, much of which originates from quaternary and methylated amines, such
      as choline and trimethylamine. In this study, we combine DNA stable isotope
      probing with high throughput sequencing of 16S rRNA genes and 13C2-choline
      enriched metagenomes, followed by metagenome data assembly, to identify the key
      microbes responsible for methanogenesis from choline. Microcosm incubation with
      13C2-choline leads to the formation of trimethylamine and subsequent methane
      production, suggesting that choline-dependent methanogenesis is a two-step
      process involving trimethylamine as the key intermediate. Amplicon sequencing
      analysis identifies Deltaproteobacteria of the genera Pelobacter as the major
      choline utilizers. Methanogenic Archaea of the genera Methanococcoides become
      enriched in choline-amended microcosms, indicating their role in methane
      formation from trimethylamine. The binning of metagenomic DNA results in the
      identification of bins classified as Pelobacter and Methanococcoides. Analyses of
      these bins reveal that Pelobacter have the genetic potential to degrade choline
      to trimethylamine using the choline-trimethylamine lyase pathway, whereas
      Methanococcoides are capable of methanogenesis using the pyrrolysine-containing
      trimethylamine methyltransferase pathway. Together, our data provide a new
      insight on the diversity of choline utilizing organisms in coastal sediments and
      support a syntrophic relationship between Bacteria and Archaea as the dominant
      route for methanogenesis from choline in this environment.

PMID- 30206425
TI  - Australian Lamb Meat - The Response to Societal and Ethnic Influences.
AB  - Lamb has long been considered a traditional meal within Australia; however as
      consumer preferences have changed since the 1950's, consumption of lamb has
      decreased from the 1980's. This is the result of changing societal roles,
      particularly for females, decreasing household sizes and increasing awareness of
      the impact of food choices on human health. Since the 1980's improvement of farm
      practices and increases in genetic gains has addressed part of this decline by
      increasing the amount of lean meat and decreasing fat in lamb retail cuts. Yet,
      this has created a challenge for the industry to utilise the larger carcases now
      being produced. Thus, a whole value chain approach to increasing consumption has
      been undertaken through several research programs to create cuts which suit the
      modern consumer, examine nutritional and eating quality and increase adoption of
      value added cuts. Therefore, this paper outlines this history of changing
      consumer patterns and the consequent research to address these changes.

PMID- 30206426
TI  - Determination of Shelf Life Model of Pork Cutlet and Pork Lard during Accelerated
      Storage Conditions.
AB  - This study was carried out to establish shelf life for pork cutlet of ground meat
      and pork lard by using various quality indicators and to understand how quality
      changes in these products are accelerated by temperature. The samples were
      selected and purchased from markets in Korea, and the chosen quality indicators
      were total aerobic counts and coliform group in microbiological analyses,
      thiobarbituric acid reactive substances assay, volatile basic nitrogen, pH, acid
      value, and peroxide value in physical chemical analyses, and sensory evaluation.
      The pork cutlet samples were stored at -18C, -6C, and -1C, whereas pork lard
      samples were stored at 10C, 25C, 35C, and 45C. These temperature conditions were
      set to real distribution conditions. The samples were then analyzed using various
      models including of reaction orders, arrhenius equation, and Q10 value. The
      quality limits for each sample were calculated, and shelf life was estimated. The
      results of this experiment highlighted the importance of temperature control
      during the distribution process of these products and revealed that temperature
      is a useful parameter for the establishment of a basic database for shelf life.

PMID- 30206421
TI  - IQSEC2-related encephalopathy in males and females: a comparative study including
      37 novel patients.
AB  - PURPOSE: Variants in IQSEC2, escaping X inactivation, cause X-linked intellectual
      disability with frequent epilepsy in males and females. We aimed to investigate
      sex-specific differences. METHODS: We collected the data of 37 unpublished
      patients (18 males and 19 females) with IQSEC2 pathogenic variants and 5
      individuals with variants of unknown significance and reviewed published
      variants. We compared variant types and phenotypes in males and females and
      performed an analysis of IQSEC2 isoforms. RESULTS: IQSEC2 pathogenic variants
      mainly led to premature truncation and were scattered throughout the longest
      brain-specific isoform, encoding the synaptic IQSEC2/BRAG1 protein. Variants
      occurred de novo in females but were either de novo (2/3) or inherited (1/3) in
      males, with missense variants being predominantly inherited. Developmental delay
      and intellectual disability were overall more severe in males than in females.
      Likewise, seizures were more frequently observed and intractable, and started
      earlier in males than in females. No correlation was observed between the age at
      seizure onset and severity of intellectual disability or resistance to
      antiepileptic treatments. CONCLUSION: This study provides a comprehensive
      overview of IQSEC2-related encephalopathy in males and females, and suggests that
      an accurate dosage of IQSEC2 at the synapse is crucial during normal brain
      development.

PMID- 30206427
TI  - Effect of High-pressure Processing on the Quality Characteristics and Shelf-life
      Stability of Hanwoo Beef Marinated with Various Sauces.
AB  - The effects of high-pressure processing (HPP) treatment on the quality
      characteristics of low graded Hanwoo beef marinated with five different sauces
      (soy, fish, fish-soy, soy-fish and fish-soy-meat sauces) obtained from Asian
      countries were studied. The Hanwoo beef striploins were marinated with the
      aforementioned sauces (at ratio: 3:1 w/w) for 3 days at 4C before they were
      treated with HPP at 550 MPa for 5 min at 10C. All the sauces used were equalized
      to a same salt level of 12.5%, and the samples marinated with a 12.5% brine
      solution were served as a control. After treating with the HPP, all the samples
      were stored for further 7 days at 4C for analyses. Results revealed that HPP
      treatments showed some effects on technological quality traits (pH, cooking loss
      and color) but had no effect on the collagen contents of the marinated beef.
      Noticeably, the HPP treatment led to the increases in amounts of free amino acids
      associated with monosodium glutamate-like taste and sweet taste in the samples
      marinated with fish sauce or soy-fish sauce, fish-soy sauce and fish-soy-meat
      sauce whereas, it only reduced these amino acids in the samples marinated with
      soy sauce or control. Furthermore, the total bacteria count in all the marinated
      beef samples treated with HPP were significantly (p<0.05) lower than those of the
      non-HPP-treated samples throughout the storage periods. It is concluded that HPP
      could be applied for enhancing the taste-active compounds production such as free
      amino acids, and improving the shelf-life stability of the marinated beef.

PMID- 30206428
TI  - Development of Commercially Viable Method of Conjugated Linoleic Acid Synthesis
      Using Linoleic Acid Fraction Obtained from Pork By-products.
AB  - The purpose of this study was to develop a commercially viable method for
      synthesis of conjugated linoleic acid (CLA) using the linoleic acid fraction
      obtained from six pork by-products (liver, lung, heart, stomach, small intestine,
      and large intestine). The workflow of CLA synthesis from each by-product was as
      follows: washing->crude fat extraction->fractionation into saturated and
      unsaturated fatty acids->repeat unsaturated fatty acid fractionation->CLA
      synthesis. Cis-9, trans-11, and trans-10, cis-12 CLA was synthesized from pork by
      products. The yield of CLA synthesis of pork by-products ranged from 1.55 to
      11.18 g per 100 g of by-products. The amount of synthesized CLA was the highest
      in the small intestine and large intestine by-products. Fractionation of pork by
      products nearly doubled the yield of CLA. We suggest that commercial
      fractionation methods could increase the yield of CLA at low cost, reduce waste,
      and improve the efficiency of by-product utilization.

PMID- 30206429
TI  - Identification of a Bromodomain-containing Protein 2 (BRD2) Gene Polymorphic
      Variant and Its Effects on Pork Quality Traits in Berkshire Pigs.
AB  - Bromodomain-containing protein 2 (BRD2) is a nuclear serine/threonine kinase
      involved in transcriptional regulation. We investigated the expression and
      association of the BRD2 gene as a candidate gene for meat quality traits in
      Berkshire pigs. BRD2 mRNA was expressed at relatively high levels in muscle
      tissue. Statistical analysis revealed that the c.1709G>C polymorphism of the BRD2
      gene was significantly associated with carcass weight, meat color (a*, redness),
      protein content, cooking loss, water-holding capacity, carcass temperatures 4, 12
      and 24 h postmortem, and the 24 h postmortem pH in 384 Berkshire pigs. Therefore,
      this polymorphism in the porcine BRD2 gene may be used as a candidate genetic
      marker to improve meat quality traits in pigs.

PMID- 30206431
TI  - Effects of Replacing Pork with Tuna Levels on the Quality Characteristics of
      Frankfurters.
AB  - The aim of this study was to evaluate the effects of pork and tuna levels on the
      quality characteristics of frankfurters and to establish a suitable percentage of
      added tuna. The levels of pork meat (PM) and yellow-fin tuna (YFT) in the test
      frankfurters were as follows: 100% PM (control), 90% PM+10% YFT (T1), 80% PM+20%
      YFT (T2), 70% PM+30% YFT (T3), 60% PM+40% YFT (T4), and 50% PM+50% YFT (T5). The
      pH of the frankfurter batters significantly decreased with increasing tuna
      levels, because the pH of the tuna is lower than that of the pork. The water
      holding capacity did not differ significantly in frankfurters containing up to
      30% tuna, whereas that of the 40% tuna-containing frankfurter was significantly
      lower than the control. Cooking loss did not differ significantly. At up to 10%
      tuna, apparent viscosity did not differ significantly, whereas at 20% tuna, it
      was significantly lower than the control. Fat separation and total expressible
      fluid separation at up to 30% tuna did not differ from the control; however, when
      more than 30% was added, higher losses were observed. The hardness of
      frankfurters containing more than 40% tuna was lower than that of the control,
      but there was no significant difference in springiness. The overall acceptability
      of frankfurters manufactured with up to 30% tuna did not differ significantly
      from the control. These results suggest that the addition of 30% tuna does not
      affect the quality of frankfurters made from pork.

PMID- 30206430
TI  - Effects of a Novel p.A41P Mutation in the Swine Myogenic factor 5(MYF5) Gene on
      Protein Stabilizing, Muscle Fiber Characteristics and Meat Quality.
AB  - Myogenic factor 5 (MYF5) plays an important role in regulating skeletal muscle
      fiber characteristics, consequently affecting meat production and quality. We
      identified a novel p.A41P mutation in exon1 of the porcine MYF5 gene by direct
      sequencing. The mutation was predicted to be destabilizing in protein structure
      based on the resultant amino acid substitution. We estimated the significant
      substitution effect of p.A41P on the energy stabilization of Myf5 protein
      structure. Then, we demonstrated that the mutation in Yorkshire population
      significantly affected muscle fiber type I composition (p<0.05), loin-eye area of
      lean meat content (p<0.05) and filter-fluid uptake of meat quality (p<0.01).
      Furthermore, dominant effects significantly influenced total muscle fiber number
      (p<0.05). This study suggests that the novel p.A41P mutation in porcine MYF5 may
      be a valuable genetic marker to affect the muscle fiber characteristics and
      consequently improve meat production quality and quantity.

PMID- 30206432
TI  - Direct Detection of Escherichia coli, Staphylococcus aureus, and Salmonella spp.
      in Animal-derived Foods Using a Magnetic Bead-based Immunoassay.
AB  - In this study, an immuno-magnetic bead (IMB)-based assay was developed to
      simultaneously detect Escherichia coli, Staphylococcus aureus, and Salmonella
      spp. and was tested in four animal-derived foods: beef, ham, egg, and ricotta
      cheese. The IMB-based assay exhibited good specificity by binding to five E. coli
      serotypes [capture efficiency (CE) average (avg.) 90.4%], five S. aureus strains
      (CE avg. 91.4%), and five Salmonella serotypes (CE avg. 95.4%) but not binding to
      non-target bacteria (CE<10%). Furthermore, the assay detected all three pathogens
      with a detection limit of 10 CFU/g without the need for enrichment or additional
      platforms. Since the results demonstrated that the IMB-based assay can
      effectively separate and enrich target bacteria from a variety of animal-derived
      food matrixes, the assay exhibits good specificity for potential use in providing
      rapid, immunological, presumptive identification of pathogenic bacteria.

PMID- 30206433
TI  - Physicochemical and Storage Characteristics of Hanwoo Tteokgalbi Treated with
      Onion Skin Powder and Blackcurrant Powder.
AB  - We evaluated the physicochemical and storage characteristics of Hanwoo Tteokgalbi
      treated with onion skin powder (OSP) and blackcurrant fruit powder (BFP). The
      experimental design included seven treatments: a control (ascorbic acid 0.1%),
      T1: OSP 0.3%, T2: OSP 0.6%, T3: BFP 0.3%, T4: BFP 0.6%, T5: OSP 0.15%+BFP 0.15%,
      and T6: OSP 0.3%+BFP 0.3%. The OSP was higher in both polyphenol and flavonoid
      contents compared to BFP (p<0.05). The moisture and ash contents of all
      Tteokgalbi samples with a large amount of added natural antioxidant powder (0.6%)
      were higher than those with small amounts of added antioxidant (0.3%). The
      cooking loss and water holding capacity were outstanding in the T2 treatment
      compared to the others (p<0.05). The lightness, redness, and yellowness values
      were reduced on the addition of 0.6% antioxidant powder (p<0.05). The springiness
      and cohesiveness values of the Tteokgalbi samples were higher for the 0.3%
      addition than the control and 0.6% addition (p<0.05). The Tteokgalbi samples with
      natural antioxidants showed similar sensory attribute scores compared to the
      control. The pH values reduced as the BFP increased (p<0.05), and the total
      microbial count increased after OSP addition. The 2-thiobarbituric acid reactive
      substance values of the samples treated with OSP were significantly lower than
      the control after day 10 (p<0.05). As a result, the addition of OSP or BFP did
      not have a significant negative influence on the quality characteristics of
      Hanwoo Tteokgalbi. In particular, the addition of 0.6% OSP was effective in
      increasing water retentivity and inhibiting lipid oxidation.

PMID- 30206434
TI  - Distribution of Microorganisms in Cheongyang Red Pepper Sausage and Effect of
      Central Temperature on Quality Characteristics of Sausage.
AB  - The objective of this study was to provide preliminary data for food industry by
      investigating the distribution of microorganisms in raw materials and sausage
      examining the effect of heating temperature on sausage quality. Total microbes in
      sausage ranged 2.21-3.11 Log CFU/g. Bacillus pumilus, B. licheniformis,
      Staphylococcus saprophyticus, and Enterococcus faecalis were detected on sausage.
      Total microbes in raw materials was 1.59-7.16 Log CFU/g. Different types of
      microorganisms were found depending on raw materials, with B. pumilus and B.
      subtilis were being detected in both raw materials and sausage. Total microbes in
      sausage after heating was in the range of 1.10-2.22 Log CFU/g, showing the trend
      of decrease in total microbe with increasing heating temperature, although the
      decrease was not significant. With increasing heating temperature, pH and
      hardness were also increased. The yield of sausage manufactured at 85 degrees C
      was 95.42% while that manufactured at 65 degrees C was 96.67%. Therefore,
      decreasing heating temperature during sausage production might increase yield and
      save energy without microbiological effect.

PMID- 30206435
TI  - Prevalence of Clostridium difficile Isolated from Beef and Chicken Meat Products
      in Turkey.
AB  - The concern about the possibility of food can be a vehicle for the transmission
      of Clostridium difficile to humans has been raised recently due to the
      similarities among the strains isolated from patients, foods and food animals. In
      this study, therefore, the prevalence of C. difficile was investigated in beef
      and chicken meat products collected from 57 different butcher shops, markets and
      fast food restaurants in Sakarya province of Turkey. Two out of 101 samples
      (1.98%) was positive for C. difficile indicating a very low prevalence. The
      pathogen was isolated from an uncooked meatball sample and a cooked meat doner
      sample, whereas not detected in chicken meat samples. The meatball isolate was
      resistant to vancomycin and tetracycline, while the cooked meat doner isolate was
      resistant to vancomycin and metronidazole. Both isolates were sensitive to
      moxifloxacin and clindamycin. Toxins A and B were not detected. This study
      reveals the presence of C. difficile in further processed beef products in
      Turkey.

PMID- 30206436
TI  - Quality Characteristics of Low-salt Chicken Sausage Supplemented with a Winter
      Mushroom Powder.
AB  - Chicken meat is a low-fat and high-protein food and consumption of chicken meat
      has been increasing globally. Various food ingredients are widely added for their
      specific purpose to processed chicken meat. Nonetheless, concerns about the
      association between high sodium intake and various diseases as well as negative
      perceptions of artificial additives are increasing. Therefore, in meat products,
      it is necessary to reduce the amount of salt and to replace artificial additives
      with natural ingredients. Our aim was to investigate the quality characteristics
      of low-salt chicken sausages manufactured with the addition of a winter mushroom
      powder. Sausages was manufactured with sodium pyrophosphate (0.3%) or winter
      mushroom powder (0%, 0.5% and 1.0%) to ground chicken breast. As a result of
      addition of the winter mushroom powder to low-salt chicken sausages, pH of the
      meat batter increased, and the proportion of jelly and melted fat exuded from
      sausages was reduced. The texture of sausages was softened and lipid oxidation in
      sausages was inhibited by the winter mushroom powder. This powder did not
      negatively affect the color and sensory properties of the sausages. According to
      the results of this study, the winter mushroom powder can serve as a natural
      ingredient to improve quality of low-salt chicken sausages.

PMID- 30206437
TI  - Comparison of Allergic Parameters between Whey Protein Concentrate and Its
      Hydrolysate in Rat Basophilic Leukemia (RBL)-2H3 Cells.
AB  - This study was conducted to compare the anti-allergic effects of a whey protein
      concentrate (WPC) and WPC hydrolysate. WPC hydrolysate was prepared using
      enzymatic digestion for 8 h with trypsin and alpha-chymotrypsin, after which it
      was freeze-dried. The allergic parameters assessed in rat basophilic leukemia
      (RBL)-2H3 cells were degranulation and release of beta-hexosaminidase, release of
      tumor necrosis factor (TNF)-alpha, and changes in the expression of IL-1beta, IL
      4, and IL-10 by real time polymerase chain reaction (PCR). During preparation of
      the WPC hydrolysate, hydrolysis increased rapidly from 0 to 10 min and then
      gradually increased slowly from 1 h onwards, achieving a final degree of
      hydrolysis of 78.50%. The SDS-PAGE analysis revealed a reduction in the intensity
      of several protein bands in the WPC hydrolysate compared to the WPC. IgE-induced
      beta-hexosaminidase release from RBL-2H3 cells was decreased to a higher degree
      following treatment with the hydrolysate compared to WPC treatment. W500 (500
      ug/mL WPC) showed the least inhibition of beta-hexosaminidase release, but there
      was no significant difference between W500 and W1000 (1,000 ug/mL) (p<0.05).
      H1000 (1,000 ug/mL WPC hydrolysate) inhibited beta-hexosaminidase release by 39%.
      Compared to the control, treatment with H1000 decreased TNF-alpha secretion to
      11.87 pg/mL. The gene expression levels of IL-1beta, IL-4, and IL-13 were all
      significantly decreased in hydrolysate (p<0.05). In the case of IL-1beta and IL
      4, the expression levels in W1000 treated cells were decreased by 73.67% and 65%,
      respectively, and that of IL-13 was decreased by 66.43% compared to the control.

PMID- 30206438
TI  - Identification of Association between Supply of Pork and Production of Meat
      Products in Korea by Canonical Correlation Analysis.
AB  - To identify correlation between fresh meat and processed meat products, we
      performed canonical correlation analysis (CCA) to predict the relationship
      between pork supply and meat product production in Korea. Results of CCA showed a
      canonical correlation of 0.8576 in the first canonical pair (p<0.01). The
      production of meat products showed the highest correlation with pork import but
      the lowest correlation with the production of domestic pork. Although Korean
      consumer preferred meat products produced by fresh domestic pork, inexpensively
      imported pork with high share in meat products was supplied in the market.
      Therefore, securing domestically produced raw meat is important for expanding
      consumption of domestic meat products. Results of this study suggest that meat
      processor and pig producer can achieve the 6th industrialization by combining the
      production of raw pork materials, meat processing, and sales service.

PMID- 30206439
TI  - Development of a Rapid Method for the Screening of Conjugated Linoleic Acid (CLA)
      Producing Strains of Bifidobacterium breve.
AB  - This study was performed to isolate some strains of Bifidobacteriumbreve from
      fecal materials of neonates and to screen them for the biotransformation activity
      of converting linoleic acid into conjugated linoleic acid (CLA). Fecal samples
      were collected from twenty healthy neonates between 14 and 100 days old, and four
      hundred colonies were randomly selected from a Bifidobacterium selective
      transoligosaccharide medium. A duplex polymerase chain reaction technique was
      developed for the rapid and accurate molecular characterization of the B. breve
      strains that have been reported to show the species-specific characteristic of
      CLA production. They are identified by 16S ribosomal DNA, fructose-6-phosphate
      phosphoketolase encoding genes (xfp), and rapid pulsed field gel electrophoresis.
      Thirty-six isolates were identified as B. breve, and just two of the 12 neonates
      were harboring B. breve strains. Each isolate showed different CLA-producing
      ability in the spectrophotometric assay. All of the positive strains from the
      primary spectrophotometric assay were confirmed for their CLA-producing
      activities using gas-chromatographic analysis, and their conversion rates were
      different, depending on the strain isolated in this study. Some strains of B.
      breve were successfully isolated and characterized based on the CLA-producing
      activity, and further studies are necessary to characterize the enzyme and the
      gene responsible for the enzyme activity.

PMID- 30206440
TI  - Construction of a Bioluminescent Labelling Plasmid Vector for Bifidobacteria.
AB  - Bifidobacterium is recognized as one of the most beneficial microorganisms in our
      gut. Many researches on bifidobacteria have been done to understand their roles
      in the gut. The objective of the present study was to develop a bioluminescent
      labelling plasmid vector for bifidobacteria to facilitate their visualization in
      vitro, in situ, and in vivo. A plasmid replicon (2.0 kb) of plasmid pFI2576
      previously identified from B. longum FI10564 was amplified by PCR and cloned into
      pUC19 plasmid vector (2.68 kb). The cloned replicon was subcloned into pTG262
      (luc+ ) recombinant plasmid vector (7.4 kb) where a luciferase gene (luc+ ) from
      pLuc2 (8.5 kb), an Escherichia coli and lactobacilli shuttle vector, was inserted
      into pTG262 plasmid vector. The final recombinant DNA, pTG262::pFI2576 rep (luc+
      ), was transferred into a B. catenulatum strain. This recombinant strain showed
      3,024 relative luminescence units at OD600 value of 0.352. Thus, this recombinant
      plasmid construct can be broadly used for labelling bifidobacteria.

PMID- 30206441
TI  - Determination of Water-holding Capacity of Porcine Musculature Based on Released
      Water Method Using Optimal Load.
AB  - The purpose of this study was to evaluate the suitability of the released water
      (RW) method for measuring water-holding capacity (WHC) by pressure and filter
      paper absorption within two thin plastic films. One hundred fifty pork loins with
      considerable variations in WHC (three pork qualities: PSE, pale, soft, and
      exudative; RFN, reddish-pink, firm, and nonexudative; and DFD, dark, firm, and
      dry; 50 pork loins in each pork quality group) were used to measure drip loss
      (DL)% and RW % after applying different loads (1.5, 2.0, 2.5, 3.0 and 3.5 kg).
      Percentages of DL and RW were significantly (p<0.05) different among pork quality
      groups. The RW % of 2.5 kg load sample was significantly (p<0.05) higher than
      that of 2.0 kg or 1.5 kg load sample. However, there were no significant (p>0.05)
      differences in RW % among 2.5 kg, 3.0 kg, and 3.5 kg load samples for all three
      pork quality groups. The RW % was highly and positively correlated (r>0.95;
      p<0.001) with DL %. The highest correlation was observed between DL % and RW % of
      2.5 kg load sample (r=0.97; p<0.001). Among all RW loads within each quality
      groups, the highest correlation between DL % and RW % was observed for 2.5 kg
      load sample (r=0.43, 0.66, and 0.46 for PSE, RFN and DFD quality groups,
      respectively, p<0.001). These results imply that applying 2.5 kg load is the best
      for determination of RW %. It is recommended as a reference method to assess DL %
      of pork muscles.

PMID- 30206442
TI  - Rapid Detection of Escherichia coli in Fresh Foods Using a Combination of
      Enrichment and PCR Analysis.
AB  - The objective of this study was to determine the minimum enrichment time for
      different types of food matrix (pork, beef, and fresh-cut lettuce) in an effort
      to improve Escherichia coli detection efficiency. Fresh pork (20 g), beef (20 g),
      and fresh-cut lettuce (20 g) were inoculated at 1, 2, and 3 Log CFU/g of
      Escherichia coli. Samples were enriched in filter bags for 3 or 5 h at 44.5
      degrees C, depending on sample type. E. coli cell counts in the samples were
      enriched in E. coli (EC) broth at 3 or 5 h. One milliliter of the enriched
      culture medium was used for DNA extraction, and PCR assays were performed using
      primers specific for uidA gene. To detect E. coli (uidA) in the samples, a 3-4
      Log CFU/mL cell concentration was required. However, E. coli was detected at 1
      Log CFU/g in fresh pork, beef, and fresh-cut lettuce after 5, 5, and 3-h
      enrichment, respectively. In conclusion, 5-h enrichment for fresh meats and 3-h
      enrichment for fresh-cut lettuce in EC broth at 44.5 degrees C, and PCR analysis
      using uidA gene-specific primers were appropriate to detect E. coli rapidly in
      food samples.

PMID- 30206443
TI  - Genetic polymorphism in psoriasis and its meaning for the treatment efficacy in
      the future.
AB  - The concept of personalized medicine is a new individualized approach which helps
      application of the targeted therapy. In fact, tailored medicine is mostly present
      in the field of life-threatening diseases such as oncology. However, skin
      diseases as such might be regarded as a potential area of implementation of this
      approach in the future. Stratified medicine in polygenetic and heterogeneous
      diseases, such as psoriasis, is more complex. Rapid development of science and
      novel molecular techniques led to better understanding of molecular pathogenetic
      pathways of many diseases including psoriasis. Identification of the particular
      immunopathogenetic pathways led to further development of targeted therapies such
      as biologic drugs. Actually the goal of individualized therapy is to determine
      the identical homogenous subgroups of patients, according to a biomarker, in
      which the response to that therapy will be the best and will carry the lowest
      risk of side effects. This review attempts to analyze the associations between
      polymorphisms of certain genes and the increased risk of developing psoriasis or
      psoriatic arthritis. The review of literature has also included the studies
      investigating the associations between gene polymorphisms and response to
      biologic therapy in psoriasis and psoriatic arthritis patients.

PMID- 30206444
TI  - Antigen recognition in the pathogenesis of immunoglobulin A-related autoimmune
      bullous diseases.
AB  - Immunoglobulin A (IgA) is the most common subtype of antibodies in mucosal
      surfaces. In most of autoimmune bullous diseases, however, immunoglobulin G (IgG)
      is the main pathogenic antibody that plays a role through complementation. The
      IgA antibody for epidermal connection protein can be found in the sera of some
      patients with blistering skin disease. Of these patients, some have the IgA
      antibody in their sera, while others have IgG and IgA antibodies. IgA-related
      autoimmune bullous diseases are less common in clinical practice. In the past,
      these diseases were not fully understood and their classifications were
      confusing. Recently, some progress has been made in the study of these diseases.

PMID- 30206445
TI  - Decreased blood CD4+PD-1+ and CD8+PD-1+ T cells in psoriatic patients with and
      without arthritis.
AB  - Introduction: Psoriasis with and without arthritis have common immunological
      mechanisms which among others involve the interactions between cytokines produced
      by T cells, including Th1, Th17 and Th22. Although quite a lot is known about
      psoriasis pathogenesis, the cause of chronic immune activation and response in
      the disease remains unclear. One of the negative regulators of the immune system
      is programmed death 1 (PD-1). Aim: To assess the expression level of PD-1 in the
      peripheral T cells of psoriatic patients with and without arthritis. Material and
      methods: The study included 23 psoriatic patients with arthritis, 52 psoriatic
      patients without arthritis and 52 healthy controls. The percentages of CD3+,
      CD4+, CD8+, CD4+PD-1+ and CD8+PD-1+ T cells were analyzed using flow cytometry.
      Results: The percentages of CD4+PD-1+ as well as CD8+PD-1+ T cells in the
      psoriatic patients both with and without arthritis were significantly lower than
      in the control group. The percentages of CD4+PD-1+ as well as CD8+PD-1+T cells
      were not significantly different between the psoriatic patients with and without
      arthritis. A significant positive correlation between PD-1 expression on the CD4+
      and CD8+ T cells was found in the psoriatic patients without arthritis.
      Conclusions: Impairment of the negative co-stimulation from PD-1 may be another
      common characteristic of psoriasis both with and without arthritis.

PMID- 30206446
TI  - Allergic phenotypes in adult patients with atopic dermatitis, determined with the
      ISAC test (ImmunoCAP ISAC).
AB  - Introduction: Atopic dermatitis (AD) is a chronic inflammatory dermatosis, often
      with a concomitant allergy. The ImmunoCAP ISAC (Immuno Solid-Phase Allergen Chip)
      test is a novel method to determine the allergenic phenotype in a given patient.
      Aim: In this study, we used the ImmunoCAP ISAC test to analyze allergic
      phenotypes in adult patients with AD. Material and methods: The study included 19
      adult patients with AD. The severity of AD was assessed using SCORAD index. Serum
      concentrations of total IgE were determined by means fluoro-enzyme immunoassay
      (FEIA). The levels of asIgE were measured with the ImmunoCAP ISAC kits. Results:
      Positive results of the ISAC test were documented in 84.2% of the study subjects.
      All patients synthesized asIgE against species-specific respiratory allergens;
      major components of animal allergens (57.87%), tree pollen allergens (47.3%),
      grass pollen allergens (42.1%), dust mite allergens (26.3%) and major allergen of
      mugwort (26.3%). 47.3% of the subjects were sensitive to cross-reactive
      allergenic components, most often proteins of the lipocalin family (57.8%),
      followed by PR-10 (26.3%), PR-14 (21%) and PR-5 proteins (21%). asIgE against
      species-specific allergens were found in 10.5% of the study subjects. No
      statistically significant relationships were observed between the severity or
      duration of AD and the prevalence and levels of asIgE against the allergens
      included in the ISAC panel. However, duration of AD correlated significantly with
      the serum concentration of total IgE. Conclusions: The ISAC test is suitable for
      determination of the allergenic phenotype in a given patient, and as such has an
      unquestioned diagnostic and therapeutic value.

PMID- 30206447
TI  - The level of proinflammatory cytokines: interleukins 12, 23, 17 and tumor
      necrosis factor alpha in patients with metabolic syndrome accompanying severe
      psoriasis and psoriatic arthritis.
AB  - Introduction: The incidence of metabolic syndrome is estimated at 15-24% in the
      general population and at 30-50% in patients with psoriasis. A probable cause of
      the described correlation is a constant release in chronic dermatosis of
      proinflammatory cytokines and their influence on individual systems and organs.
      Aim: Assessment of the concentration of the proinflammatory cytokines (IL-12, IL
      23, IL-17 and TNF-alpha) in blood serum and their correlation with the intensity
      of skin lesions, the presence of psoriatic arthritis and the risk of development
      of obesity and metabolic syndrome. Material and methods: The concentrations of
      subunit p70 IL-12, IL-17 and IL-23, and TNF-alpha in subjects with psoriasis and
      metabolic syndrome were determined. Results: The level of the studied cytokines,
      IL-17, IL-23 and TNF-alpha was higher in patients diagnosed with psoriasis.
      Higher levels of IL-17, IL-23 and TNF-alpha were observed in patients with
      metabolic syndrome accompanying psoriasis. A higher level of IL-17 and IL-23 was
      found in sera of patients with psoriatic arthritis in comparison to normal
      psoriasis. Conclusions: In the study, a higher level of IL-17 and IL-23 was also
      shown in patients with psoriatic arthritis in comparison to patients with normal
      psoriasis. The effectiveness of anti-IL12/23 drugs in psoriatic arthritis is a
      confirmation of the obtained results of the studies. Additionally, the increased
      level of IL-17, both in patients with metabolic syndrome and with psoriasis,
      could indirectly indicate an increased cardiovascular risk in patients with
      affected joints in comparison to psoriasis affecting only the skin.

PMID- 30206448
TI  - Mean platelet volume and platelet distribution width levels in patients with mild
      psoriasis vulgaris with metabolic syndrome.
AB  - Introduction: Psoriasis vulgaris (PV) is a common inflammatory skin disease
      characterized by incomplete differentiation and hyperproliferation of epidermal
      keratinocytes. Platelets play a role in inflammatory reactions and the immune
      response and may be activated by a variety of stimulants. Studies in recent years
      have shown increased incidence of metabolic syndrome (MetS) in psoriasis
      patients. However, the mean platelet volume (MPV) and platelet distribution width
      (PDW) values have not been assessed in PV accompanied by MetS. Aim: To evaluate
      MPV and PDW levels and their association with metabolic parameters in the
      presence of MetS in PV patients. Material and methods: A total of 76 patients
      with mild PV, including 38 with MetS and 38 without MetS, 38 patients with MetS
      without PV and 35 healthy individuals were enrolled in the study. The number of
      platelets, MPV, PDW, fasting blood glucose, urea, creatinine, total cholesterol,
      high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol
      (LDL-C), triglycerides, thyroid stimulating hormone, free triiodothyronine, and
      the free thyroxine levels were evaluated. Results: Mean platelet volume and PDW
      levels were significantly higher in the mild PV with MetS group compared to the
      mild PV without MetS group, MetS without PV patients and the healthy control
      group (p < 0.05, for all). There was no significant difference between the mild
      PV without MetS group and the healthy control group in terms of MPV and PDW
      levels (p > 0.05, for all). There was no significant difference between the
      groups with MetS and without MetS in terms of the psoriasis area and severity
      index (PASI) (p > 0.05). The PASI was not correlated with MPV and PDW. In
      addition, metabolic parameters were not correlated with MPV and PDW in mild PV
      patients. Conclusions: Mean platelet volume and PDW levels showing platelet
      activation increase significantly in the presence of MetS in patients with mild
      PV.

PMID- 30206449
TI  - Omalizumab for urticaria treatment in clinical practice: a case series.
AB  - Introduction: Omalizumab (Xolair) originally intended to reduce symptoms of
      moderate to severe asthma uncontrollable with steroids is the first monoclonal
      antibody approved for treatment of chronic spontaneous urticaria in 2014. Aim: To
      evaluate response and potential side effects to omalizumab treatment in clinical
      practice. Material and methods: Eleven patients (6 males and 5 females) were
      recruited into the study. All participants signed written informed consent before
      enrollment to the study. At the beginning they were receiving 300 mg of
      omalizumab in a subcutaneous injection every 4 weeks in an outpatient clinic.
      Five the clinical response was sufficient, the dose of omalizumab was decreased
      to 150 mg. We evaluated response to the treatment using the Urticaria Activity
      Score in the last 7 days and the Urticaria Control Test at certain time points.
      Results: Nine out of 11 patients achieved complete syndrome resolution. Five
      patients achieved clinical remission after the first dose of omalizumab. Mean
      time to remission was 9.3 weeks. During the study, no side effects were observed.
      Conclusions: Omalizumab appears to be a safe drug, which in a quick and effective
      way inducts remission in patients who have not responded to previous treatment.

PMID- 30206450
TI  - Bacteriological analysis of isolated chronic sinusitis without polyps.
AB  - Introduction: Chronic sinusitis (CRS) is phenotypically divided into inflammation
      with polyps (CRSwNP) or without polyps (CRSsNP). Aim: To try to explain the
      reasons for isolated sinusitis by analysing medical history as well as anatomical
      and bacteriological data. Material and methods: In 2016, endoscopic surgery was
      performed in 103 patients with CRSsNP within 6 months. The authors evaluated 28
      patients with lesions in one sinus. Results: The patients did not report any
      previous facial trauma, dental procedures, there were no odontogenic causes of
      the disease. They had not been treated with antibiotics within 30 days prior to
      admission to hospital. Ninety-seven bacterial strains were grown, of which 32 in
      patients with isolated nasal sinusitis. Statistical analysis has shown that there
      is a trend toward a statistically significant (p = 0.0868) relationship between
      the presence of Staphylococcus aureus and the type of inflammation. Conclusions:
      There is an indication that the presence of Staphylococcus aureus is associated
      with isolated sinusitis, especially in women.

PMID- 30206451
TI  - Whole-cell pertussis vaccine (DTwP) has no influence on allergic diseases and
      atopic sensitization in children.
AB  - Introduction: Vaccine opponents indicate that the infant's immune system is
      inadequately developed to handle multiple vaccines which may overwhelm the immune
      system, leading to allergic diseases. Aim: To verify the association between the
      vaccine antigen overload derived from DTwP and the development of atopic
      sensitization and allergic diseases. Material and methods: Data from an earlier
      established birth cohort in Krakow, followed up to the 6th year of life were
      used. Allergic diseases such as eczema, hay fever and asthma were diagnosed by a
      physician and reported every half a year from the 1st to 6th year of life by the
      child's parent. Skin prick tests (SPT) were performed in children at 5 years of
      age. The data on infants' vaccination were extracted from the physician's
      records. The status of vaccine antigen exposure was based on different types of
      vaccines against pertussis (DTwP or DTaP) in a primary course. Results were
      determined by multiple logistic regression, adjusted to potential confounders.
      Results: The analyzed population consisted of 234 children: 53.4% - boys and
      46.6% - girls. Infants up to the age of 8 months were vaccinated with the primary
      course against pertussis, with DTwP - 60.7%, DTaP - 32.9% and further 6.4% with a
      mixed course (DTwP + DTaP). There were no significant relationships between any
      of vaccination groups and allergic disease and allergen sensitivity in the
      multiple logistic regression model with adjustment to potential confounders.
      Conclusions: The exposure to a large number of vaccine antigens derived from DTwP
      has no influence on the development of allergic diseases and atopic sensitization
      in children.

PMID- 30206452
TI  - Type D personality and the degree of control of bronchial asthma.
AB  - Introduction: Poor asthma control is probably associated with both biological and
      psychological factors. Type D pattern of behavior is characterized by negative
      emotionality and inhibition in social relationships. It was previously found to
      be associated with cardiovascular diseases. Aim: To evaluate the correlation
      between the degree of asthma control and the severity of the components of type D
      behavior pattern. Material and methods: The research was conducted on a group of
      117 subjects with bronchial asthma. The control group consisted of 32 healthy
      subjects. The degree of bronchial asthma control was determined using the Asthma
      Control Test. The D pattern of behavior was measured using the DS-14
      questionnaire. Results: The risk of type D behavior pattern, defined as scoring
      at least 10 points in both scales (Negative Emotionality and Social Inhibition),
      was higher in subjects with uncontrolled asthma than in healthy individuals (OR =
      5.19; 95% CI: 1.74-15.44), those with partial control of asthma (OR = 6.04; 95%
      CI: 1.87-19.52) and subjects with good control of asthma (OR = 8.46; 95% CI: 3.09
      23.16). The severity of depressiveness correlated positively with the number of
      infections in the past year. Negative emotionality correlated positively with the
      number of infections and social inhibition. Conclusions: Type D pattern of
      behavior may be associated with diagnosis and severity of asthma. Due to its link
      to poor control of asthma symptoms, a high level of negative emotionality among
      patients with asthma might be of particular interest to the clinicians.

PMID- 30206453
TI  - Specific oral immunotherapy in food allergic patients: transient or persistent
      tolerance?
AB  - Introduction: The first therapeutic choice for food allergy is avoidance of the
      responsible food, but when this approach is not possible, specific oral
      desensitization could be considered as a good alternative. It is not clear yet
      whether the acquired tolerance is transient or persistent. Aim: We report on a
      subset of 13 patients of a larger study, treated successfully with specific oral
      tolerance induction who experienced secondary loss of tolerance after a period of
      allergen avoidance. Material and methods: Thirteen patients affected by IgE
      mediated food allergy: to cow milk (3 patients), to hen egg (3 patients), to cod
      fish (2 patients), to peanuts (1 patient) and to corn (1 patient) confirmed by a
      complete allergological workup and a double-blind placebo-controlled food
      challenge (DBPCFC), were treated with sublingual-oral desensitization. After the
      interruption of the maintenance phase, the laboratory tests were performed and 12
      of 13 patients underwent DBPCFC. Results: Oral specific desensitization was
      completed successfully in all the 13 reported patients. At different times after
      the end of treatment, they decided, on their own initiative, to stop the
      ingestion of incriminated food. A new food allergen re-exposure caused adverse
      reactions in 12 of 13 patients. The detection of specific IgE and IgG4 during the
      period of allergen avoidance showed an increase in or a stable level of specific
      IgE and a decrease in specific IgG4 in 8 patients. Conclusions: According to our
      experience, the tolerance obtained through the desensitizing treatment is
      transient and so the regular allergen intake is necessary for its maintenance.

PMID- 30206454
TI  - Calprotectin can play an inflammatory role in acne vulgaris.
AB  - Introduction: Acne vulgaris (AV) is a chronic inflammatory disorder of the
      pilosebaceous unit. Although various mechanisms have been indicated in the
      etiopathogenesis of acne vulgaris, the exact pathophysiology is still unknown.
      Aim: To investigate the level of calprotectin in acne vulgaris and its levels
      relationship with disease severity. Material and methods: A total of 66 AV
      patients, who were divided into 33 mild and 33 moderate-severe cases, and 30
      healthy controls were enrolled in the study. Disease severity was assessed using
      the Global Acne Score. According to this scale, patients whose Global Acne Score
      was 1-18 had mild acne, those with a score of 19-30 had moderate acne, those with
      a score of 31-38 had severe acne, and those with a score greater than 39 had very
      severe acne. Serum calprotectin levels of all participants were measured by
      enzyme-linked immunosorbent assay method. Results: The serum calprotectin levels
      in the moderate-severe AV group were significantly higher than that of the mild
      AV group (p < 0.001). In addition, the serum calprotectin level in the mild AV
      group was significantly higher than that of the healthy control group (p =
      0.047). However, in the Spearman's correlation analysis, the serum calprotectin
      level and GAS were not correlated in AV patients (p = 0.171, r = 0.179).
      Conclusions: Serum calprotectin levels are increased in mild and moderate AV
      patients.

PMID- 30206455
TI  - Acute-phase response and its biomarkers in acute and chronic urticaria.
AB  - Introduction: Since urticaria is a persisting inflammatory disease it is
      important to establish the prognostic factors for the duration and severity of
      the disease. Aim: To evaluate serum concentrations of selected acute-phase
      proteins (APP) in patients with various forms of urticaria as compared to healthy
      volunteers and also to analyze these concentrations in different types of
      urticaria. Additionally, to evaluate the correlation between serum levels of
      selected APP and disease activity. Material and methods: Serum concentrations of
      C-reactive protein (CRP), alpha1-acid glycoprotein (AGP), alpha1-antichymotrypsin
      (ACT), alpha1-antitrypsin (AT), ceruloplasmin (Cp), transferrin (Tf), alpha2
      macroglobulin (alpha2M) and haptoglobin (Hp) were measured. Quantitative
      measurement was conducted using the rocket immunoelectrophoresis. Disease
      activity was assessed with the use of total symptom score. Results: Analysis of
      serum APP concentrations revealed statistically higher serum concentrations of
      CRP, AGP and ACT in the entire group of patients with urticaria in comparison
      with the control group. In the entire group of patients with urticaria, CRP, AGP,
      ACT, Cp and Hp correlated positively with disease activity, intensity of pruritus
      and the number and size of urticarial wheals. Statistically lower serum
      concentrations of CRP, ACT, Cp and Hp were detected in the group of patients with
      acute urticaria (AU) and angioedema together, compared to the patients suffering
      from AU only. Conclusions: Patients with symptoms of various forms of urticaria
      present a distinct profile of serum APP concentrations. A significant correlation
      observed between CRP, AGP, ACT, Cp, Hp and clinical activity score points to the
      potential role of APP as markers of the urticarial activity.

PMID- 30206456
TI  - Outdoor work as a risk factor for high-grade cutaneous squamous cell carcinoma of
      the head and neck.
AB  - Introduction: While it is clear that individuals with outdoor occupations are at
      a significantly greater risk of developing cutaneous squamous cell carcinoma
      (cSCC), no previous studies have investigated the potential association between
      the tumour grade and occupation in this patient population. Aim: To assess
      occupation as a risk factor for the development of high-grade cSCC. Secondarily,
      to determine the association between the tumour grade and other clinical
      characteristics. Material and methods: Retrospective analysis of 256 patients
      treated for head and neck cSCC at our institution in 2007-2016. The following
      patient characteristics and variables were assessed: age; sex; tumour location
      and grade; profession; and education level. A univariate analysis was performed
      to assess the association between each study variable and grade 3 tumour
      differentiation. Results: The following variables were significantly associated
      (p < 0.05) with grade 3 (G3) cSCC tumours: outdoor work vs. indoor work; primary
      school vs. high school education; and age. Additionally, patients with low-grade
      (G1) tumours were significantly younger (mean age: 72) than patients with high
      grade (G3) tumours (mean age: 79) (p = 0.046). Conclusions: To our knowledge,
      this is the first study to assess the variables associated with the tumour grade
      among outdoor workers. These findings suggest that outdoor workers who develop
      cSCC are at a greater risk of developing more aggressive cancers. These findings
      provide additional support for classifying cSCC as an occupational disease. Early
      education about the dangers of sun exposure during the first years of school is
      essential to minimize the risks of developing high-grade skin cancer.

PMID- 30206457
TI  - Effect of adalimumab on the expression of genes encoding TNF-alpha signal paths
      in skin fibroblasts in vitro.
AB  - Introduction: Tumour necrosis factor (TNF-alpha) is one of the main cytokines
      participating in inflammation and immune response. Biological effects of the
      cytokine action, mediated by two receptors: TNFRSF1A and TNFRSF1B involve
      activation of many signal paths, thus change the transcription activity of many
      genes. The mechanism of action of an anti-TNF medicine consists in blocking TNF
      alpha though preventing activation of signal paths. Aim: To single out mRNA and
      microRNA genes relating to TNF-alpha signal paths, the expression of which could
      indicate sensitivity of cells to the medicine in question. Material and methods:
      The material used in the research consisted in the cell line of regular human
      skin fibroblasts NHDF (CC-2511 Lonza, Basel, Switzerland) exposed to adalimumab
      with a concentration of 8.00 MUg/ml of the medium for 2, 8 and 24 h, compared
      with the control material, i.e. non-stimulated cells. Molecular analysis was
      performed using the oligonucleotide expressive micro-matrices technology HG
      U133A, miRNA 2.0 Array micro-matrices and RTqPCR. Results: mRNA: BIRC5, MAP3K4,
      ZFAND5, JUN differentiate cells exposed to the anti-TNF medicine, regardless of
      the time of cell/medicine incubation. TNF-alpha transcription activity is reduced
      during exposure of NHDF cells to adalimumab. miRNA regulating transcription
      activity of the said 4 mRNA and miRNA related to TNF-alpha and its receptors was
      also singled out. Conclusions: It was ascertained that adalimumab has therapeutic
      potential and affects genes engaged in signal paths activated by TNF-alpha. The
      results indicate the TNF-alpha usefulness as the molecular, supplementary marker
      in diagnostics and control of treatment effects.

PMID- 30206458
TI  - Evaluation of the antioxidant enzyme activity level in patients with alopecia
      areata.

PMID- 30206459
TI  - Unilateral generalized morphea: a case report and literature review.

PMID- 30206460
TI  - Seizures as a rare adverse effect of chloroquine therapy in systemic lupus
      erythematosus patients: a case report and literature survey.

PMID- 30206461
TI  - Bullous systemic lupus erythematosus associated with increased activity of lupus
      nephritis: a case report and review of the literature.

PMID- 30206463
TI  - Salvage of Thumb With a Free Skin Flap From the Great Toe.

PMID- 30206462
TI  - Reverse Kobner response in lichen striatus: the first case described in the
      literature.

PMID- 30206465
TI  - Characteristics of Laboratory Confirmed Ethylene Glycol and Methanol Exposures
      Reported to a Regional Poison Control Center.
AB  - Introduction: Ethylene glycol (EG) and methanol (MET) exposures are rare but can
      cause significant morbidity and mortality. Though frequently treated similarly,
      EG and MET exposures have characteristics that are not well differentiated in the
      literature. We sought to describe the clinical characteristics of EG and MET
      exposures, confirmed with quantitative serum levels. Methods: An IRB-approved
      retrospective review of the University of Kansas Health System Poison Control
      Center database from July 2005 to July 2015 identified all EG/MET exposures
      evaluated at a health care facility. Initial measurements were EG/MET levels,
      serum pH, serum creatinine, anion gap, serum ethanol level, max anion gap, max
      osmolar gap, therapy performed (hemodialysis, fomepizole, ethanol) and death.
      Results: The search identified 75 cases, with 59 cases having only detectable EG
      levels and 15 cases having only detectable MET levels. The average EG level was
      126 mg/dL (range 5 - 834). The average detectable methanol level was 78 mg/dL
      (range 5 - 396). The average maximum anion gap of the EG positive group was 20
      mEq/L (range 8 - 35). The average maximum anion gap of the MET positive group was
      14 mEq/L (range 6 - 34). One death was reported in the EG positive group, with an
      initial level of 266 mg/dL. Conclusions: In this study of EG/MET exposures, EG
      exposures were more common than MET exposures, but they had similar demographics,
      laboratory findings, and interventions. Continued studies are warranted to
      characterize these uncommon exposures further.

PMID- 30206464
TI  - The Cost of Routine Follow-Up in Total Joint Arthroplasty and the Influence of
      These Visits on Treatment Plans.
AB  - Introduction: Many physicians recommend annual or biennial visits after total hip
      and knee arthroplasty (THA and TKA). This study sought to establish the cost of a
      post-operative visit to both the health care system and patient and identify if
      these visits altered patient management. Methods: A prospective cohort study was
      conducted using patients presenting for follow-up after THA or TKA from April
      through December 2016. All surgeries were performed by a single orthopaedic
      surgeon in Wichita, Kansas. All eligible subjects that met the inclusion criteria
      received and completed a questionnaire about the personal cost of the visit and
      their assessment of their function and outcome after total joint arthroplasty.
      The physician also completed a questionnaire that examined the cost of the visit
      to the health care system and whether the clinical or radiographic findings
      altered patient management. Results: Fifty-six patients participated with an
      average length of follow- up of 4.5 +/- 4.1 years since surgery. The average
      patient cost was $135.20 +/- $190.53 (range, $1.65 - $995.88), and the average
      visit time for the patient was 3.9 +/- 2.9 hours. Eighty percent of patients
      reported no pain during the clinic encounter, and 11% reported loss of function.
      Eighty-four percent thought the visit was necessary. Physician time for each
      visit lasted 12.9 +/- 3.7 minutes (range, 10 - 20 minutes). Only 9% of patient
      encounters resulted in an alteration in patient management. This occurred at an
      average follow-up time of 3.6 +/- 1.8 years after the index procedure. The
      average cost of each visit to the health care system at large was $117.31 +/-
      60.53 (range, $93.90 - $428.28). Conclusions: The findings of this study advise
      total joint patients and orthopaedic surgeons regarding the cost of routine post
      operative appointments and whether these visits alter patient management. The
      majority of the routine follow-up visits after THA and TKA did not result in an
      alteration in patient management, but added substantial cost to the health care
      system.

PMID- 30206466
TI  - Exploring the Impact of Group Size on Medical Students' Perception of Learning
      and Professional Development During Clinical Rotations.
AB  - Introduction: Research assessing the size of learning groups in medical education
      and how that affects the learner's experience is limited. The main goals of the
      study were to (1) assess the effect of varying group size on medical students'
      subjective experiences during clinical years. We hypothesized that students in
      smaller groups were more likely to have better experiences during clinical
      rotation than those in larger groups, and (2) determine if medical students have
      desirable experiences working with other medical learners (fellows, residents,
      osteopathic students, physician assistants, and nurse practitioners) during
      clinical rotations. Methods: The study utilized a mixed method approach where 153
      medical students in their clinical years were asked to complete a 10-item survey.
      A linear-by-linear association test of trend and Mann-Whitney U test were used to
      evaluate the students' quantitative data. A multidisciplinary team used an
      immersion-crystallization approach to analyze the content of the students'
      qualitative data. Results: There was a 90% (137/153) response rate. Most students
      (80%) reported desirable experiences during clinical rotations because of
      supportive learning environments, engaging preceptors, willingness of residents
      to teach, as well as the opportunity to participate in patient care. There were
      significant differences in students' perceived clinical experiences as a function
      of group size, where groups of two students were preferable over groups of four
      or more. Conclusions: Varying group size appears to affect students' clinical
      experiences.

PMID- 30206467
TI  - Is it a Drug or a Bug? A Case of Chemotherapy and Immune Modulators Complicating
      the Diagnosis of Ehrlichiosis.

PMID- 30206468
TI  - Evaluation of Syncope Reveals Cardiac Amyloidosis.

PMID- 30206469
TI  - Optimal Management of a Pregnant Patient with Rheumatic Heart Disease.

PMID- 30206470
TI  - Focal Myopericarditis Presenting as Acute ST-Elevation Myocardial Infarction.

PMID- 30206472
TI  - Femoral neuropathy following direct anterior total hip arthroplasty: an anatomic
      review and case series?.
AB  - The popularity of the direct anterior approach for total hip arthroplasty (THA)
      has dramatically increased in recent years. Many patients request this muscle
      sparing approach for the theorized benefits of quicker recovery and reduced post
      operative pain. Femoral nerve injury is a rare, yet serious complication
      following the anterior approach for THA. During the 7-year period from 2008 to
      2016, 1756 patients underwent primary THA with a direct anterior approach by a
      single senior surgeon for end-stage osteoarthritis. Six (0.34%) of these patients
      had a post-operative femoral nerve palsy. We aim to discuss anatomic
      considerations, risk factors, and a timeline of severity and recovery for femoral
      nerve palsy following direct anterior THA in six patients.

PMID- 30206471
TI  - Sexual abuse in very young children: a psychological assessment in the Amsterdam
      Sexual Abuse Case study.
AB  - Background: Child sexual abuse (CSA) is a worldwide problem affecting children of
      all ages and socioeconomic backgrounds. A knowledge gap exists regarding the
      psychological outcomes for children, boys in particular, who are abused during
      their early lives. Objective: To provide a descriptive psychological profile of
      children who experienced sexual abuse as infants or toddlers from a male daycare
      worker and babysitter, and to assess the psychopathological impact on their
      parents. Method: Parents of children involved in the Amsterdam Sexual Abuse Case
      (41 parents; 44 children, age range 3-11 years, 30 boys, 14 girls) completed
      measures on post-traumatic stress disorder (PTSD), dissociation, sexual and non
      sexual behaviour problems, and attachment insecurity in their children, as well
      as on parental psychological well-being, 3 years after disclosure. Sexual abuse
      characteristics were obtained from police records. Results: We found that 3% of
      confirmed child victims had PTSD, 30% sexual behaviour problems, 24%
      internalizing problems, 27% attachment insecurity, and 18% any psychiatric
      disorder (including PTSD); 39% were asymptomatic. In parents, we found feelings
      of guilt, shame, and anger about the abuse of their child; 19% showed PTSD
      symptoms and 3% showed avoidant and 8% anxious attachment problems in their
      intimate relationship. Parental symptomatology was related to child
      symptomatology, except for child sexual behaviour problems. One-quarter of
      confirmed child victims and 45% of parents had received psychological treatment.
      Conclusions: Three years after disclosure, extrafamilial CSA in very young
      children was associated with sexual and non-sexual behaviour problems and
      attachment insecurity, but rarely with PTSD or dissociation. For parents it was
      associated with PTSD symptoms and emotional reactions. Assessments and
      interventions should focus on the wide spectrum of problems that follow CSA, as
      well as on parental psychopathology and the parent-child relationship. Future
      follow-up assessments in our longitudinal study should provide insights into
      longer-term outcomes.

PMID- 30206473
TI  - Protracted diagnosis of ACNES: a costly exercise.
AB  - This case report summarizes the course of events leading to diagnosis and
      eventual repair of anterior cutaneous nerve entrapment syndrome (ACNES) in a 58
      year-old female. The time period elapsing from initial symptoms to final
      operative repair was 9 months. The diagnosis was missed by both medical and
      surgical specialists despite multiple outpatient appointments, investigative
      procedures and a battery of laboratory tests. The diagnosis of ACNES was first
      considered when reviewed by a hernia surgeon and subsequently confirmed following
      open exploration of the anterior abdominal wall. The nerve was released and pain
      symptoms resolved. Access to the NHS Scotland ISD register permitted an economic
      analysis of the diagnostic services utilized for this patient and these totalled
      nearly L11 500. At a time when the NHS is focused on cost effectiveness, this
      particular sequence of investigations illustrates a protracted and costly
      diagnostic pathway.

PMID- 30206474
TI  - Two successful cases of DIEP flaps for breast reconstruction in patients with
      Factor V Leiden.
AB  - Factor V Leiden (FVL) is the most common inherited hypercoagulable condition. It
      is a genetic disorder caused by a missense mutation that prevents inactivation of
      Factor V in the clotting cascade, leading to overproduction of thrombin and
      excess clotting. This pathophysiological process is especially unfavorable in
      patients undergoing free tissue transfer. Many authors have noted a propensity
      for both venous and arterial thrombosis leading to partial or complete flap loss.
      To date, there have been no published reports of patients with FVL undergoing
      deep inferior epigastric perforator flap reconstruction without flap
      complications. Here, the authors present two cases of successful free tissue
      transfer for breast reconstruction in patients with diagnosed FVL. The
      perioperative thromboelastography lab values are evaluated to help guide
      anticoagulation regimen for these high-risk procedures.

PMID- 30135732
TI  - What is a predatory journal? A scoping review.
AB  - Background: There is no standardized definition of what a predatory journal is,
      nor have the characteristics of these journals been delineated or agreed upon. In
      order to study the phenomenon precisely a definition of predatory journals is
      needed. The objective of this scoping review is to summarize the literature on
      predatory journals, describe its epidemiological characteristics, and to extract
      empirical descriptions of potential characteristics of predatory journals.
      Methods: We searched five bibliographic databases: Ovid MEDLINE, Embase Classic +
      Embase, ERIC, and PsycINFO, and Web of Science on January 2 nd, 2018. A related
      grey literature search was conducted March 27 th, 2018. Eligible studies were
      those published in English after 2012 that discuss predatory journals. Titles and
      abstracts of records obtained were screened. We extracted epidemiological
      characteristics from all search records discussing predatory journals.
      Subsequently, we extracted statements from the empirical studies describing
      empirically derived characteristics of predatory journals. These characteristics
      were then categorized and thematically grouped.   Results: 920 records were
      obtained from the search. 344 of these records met our inclusion criteria. The
      majority of these records took the form of commentaries, viewpoints, letters, or
      editorials (78.44%), and just 38 records were empirical studies that reported
      empirically derived characteristics of predatory journals. We extracted 109
      unique characteristics from these 38 studies, which we subsequently thematically
      grouped into six categories: journal operations, article, editorial and peer
      review, communication, article processing charges, and dissemination, indexing
      and archiving, and five descriptors.    Conclusions: This work identified a
      corpus of potential characteristics of predatory journals. Limitations of the
      work include our restriction to English language articles, and the fact that the
      methodological quality of articles included in our extraction was not assessed.
      These results will be provided to attendees at a stakeholder meeting seeking to
      develop a standardized definition for what constitutes a predatory journal.

PMID- 28781760
TI  - Proteolytic processing of the L-type Ca 2+ channel alpha 11.2 subunit in neurons.
AB  - Background: The L-type Ca2+ channel Cav1.2 is a prominent regulator of neuronal
      excitability, synaptic plasticity, and gene expression. The central element of
      Cav1.2 is the pore-forming alpha 11.2 subunit. It exists in two major size forms,
      whose molecular masses have proven difficult to precisely determine. Recent work
      suggests that alpha 11.2 is proteolytically cleaved between the second and third
      of its four pore-forming domains (Michailidis et al,. 2014). Methods: To better
      determine the apparent molecular masses (M R)of the alpha 11.2 size forms,
      extensive systematic immunoblotting of brain tissue as well as full length and C
      terminally truncated alpha 11.2 expressed in HEK293 cells was conducted using six
      different region-specific antibodies against alpha 11.2. Results: The full length
      form of alpha 11.2 migrated, as expected, with an apparent M R of ~250 kDa. A
      shorter form of comparable prevalence with an apparent M R of ~210 kDa could only
      be detected in immunoblots probed with antibodies recognizing alpha 11.2 at an
      epitope 400 or more residues upstream of the C-terminus. Conclusions: The main
      two size forms of alpha 11.2 are the full length form and a shorter form, which
      lacks ~350 distal C-terminal residues. Midchannel cleavage as suggested by
      Michailidis et al. (2014) is at best minimal in brain tissue.

PMID- 30206477
TI  - Variations of dry eye disease prevalence by age, sex and geographic
      characteristics in China: a systematic review and meta-analysis.
AB  - Background: Dry eye disease (DED) is one of the most prevalent ocular diseases in
      the world. In China, new lifestyles driven by information technology and the
      rapid ageing process have brought DED a severe public health concern. The aim of
      our study was to obtain the pooled prevalence of DED in China and explore its
      potential correlates. Methods: A comprehensive systematic review was conducted to
      identify all relevant literature published since 1990. Meta-analysis and meta
      regression approaches were adopted to estimate the prevalence of DED. The number
      of people with DED was obtained by multiplying the corresponding demographic data
      in 2010. Results: Advanced age, female sex and larger latitude were significant
      risk factors for DED by symptoms and signs, whereas only advanced age was
      positively associated with an increased prevalence of DED by symptoms. In 2010,
      the prevalence of DED by symptoms and signs were 13.55% (95% CI = 10.00-18.05)
      and that of DED by symptoms was 31.40% (95% CI = 23.02-41.13) in Chinese people
      aged 5-89 years, corresponding to a total of 170.09 million (95% CI = 125.52
      226.63) and 394.13 million (95% CI = 288.99-516.30) affected individuals
      respectively. Conclusions: The huge burden of DED in China calls for more public
      health attention and actions. Improved epidemiological studies on DED prevalence
      are still urgently needed.

PMID- 30206478
TI  - Why some mothers overestimate birth size and length of pregnancy in rural Nepal.
AB  - Background: Quantitative validation studies alone may not be able to distinguish
      between instances when participants did not accurately report an event vs when
      participants did not understand a question. We used an explanatory qualitative
      study design to acquire an in-depth understanding of why some mothers in rural
      Nepal overestimate birth size of their newborn and their length of pregnancy.
      Methods: We conducted two focus group discussions (FGDs) with study staff who
      administered a quantitative questionnaire and 12 in-depth interviews (IDIs) with
      mothers who had participated in a quantitative validation study. Transcripts were
      coded and analyzed for themes in patterns of meaning within and across FGDs and
      IDIs. Using this thematic map, we synthesized our data into common and divergent
      responses from participants to facilitate our interpretation of the quantitative
      findings. Results: We identified five themes specific to this analysis:
      difficulties with the length of pregnancy question, challenges in administering
      the birth size question, the perceived effect of time since birth on mothers'
      ability to remember information, the language and style differences specific to
      this setting, and the study context shaping the relationship between study staff
      and mothers who participated and how this may have influenced mothers' responses.
      Visual aids may help to scale the question about birth size within a cultural
      frame of reference for maternal reports to be more interpretable. Among both
      study staff and mothers, a longer period of time since the birth of a child was
      thought to be associated with diminished accuracy of maternal reports, a
      perception not supported by our previously published quantitative findings.
      Conclusions: Poor validity of low birth weight (LBW) and preterm birth indicators
      based on maternal reports may be partly attributed to challenges in maternal
      understanding of questions assessing birth size and length of pregnancy.
      Additional research is needed to confirm these findings regarding maternal
      comprehension and to further evaluate the utility of visual aids developed for
      this study.

PMID- 30206479
TI  - Heart Failure with Mid-range Ejection Fraction: Lessons from CHARM.
AB  - The newly defined category of heart failure (HF) with mid-range ejection fraction
      (HFmrEF; EF 40-49 %) is beginning to be characterised but little is known about
      the potential for treating it. Trials and observational studies suggest that
      standard therapy for HF with reduced ejection fraction (HFrEF; EF <40 %) may also
      offer some benefit to patients with EF >=40 %; however, any difference between
      its effects on HFmrEF and true HF with preserved ejection fraction (HFpEF) have
      until now not been explored. This study summarises randomised trial data from the
      CHARM programme that suggest that candesartan may improve outcomes in HFmrEF.

PMID- 30206480
TI  - Advances in Imaging and Heart Failure: Where are we Heading?
AB  - Advanced cardiac imaging, following technological advances, has progressed
      significantly; it now serves as a diagnostic as well as a prognostic tool. Heart
      failure patients demand constant follow-up with baseline imaging such as
      echocardiography or more advanced imaging such as stress imaging. Imaging guides
      treatment as well as interventional procedures for the improvement of heart
      failure patients. This review aims to summarise the latest imaging techniques in
      heart failure diagnosis and treatment.

PMID- 30206481
TI  - Imaging of Valvular Heart Disease in Heart Failure.
AB  - Valvular heart disease (VHD) and heart failure (HF) are major health issues that
      are steadily increasing in prevalence in Western populations. VHD and HF
      frequently co-exist, which can complicate the accurate diagnosis of the severity
      of valve stenosis or regurgitation and affect decisions about therapeutic
      options. Transthoracic echocardiography is the first-line imaging modality to
      determine left ventricular (LV) systolic function, to grade valvular stenosis or
      regurgitation and to characterise the mechanism underlying valvular dysfunction.
      3D transoesophageal echocardiography, cardiovascular magnetic resonance and
      cardiac CT are alternative imaging modalities that help in the diagnosis of
      patients with HF and VHD. The integration of multimodality cardiovascular imaging
      is important when deciding whether the patient should receive transcatheter
      aortic valve repair and replacement therapies. In this article, the use of
      multimodality imaging to diagnose and treat patients with VHD and HF is reviewed.

PMID- 30206482
TI  - Heart-brain Interactions in Heart Failure.
AB  - Heart failure (HF) is a complex disease with a growing incidence worldwide. HF is
      accompanied by a wide range of conditions which affect disease progression,
      functional performance and contribute to growing healthcare costs. The
      interactions between a failing myocardium and altered cerebral functions
      contribute to the symptoms experienced by patients with HF, affecting many
      comorbidities and causing a poor prognosis. This article provides a condensed
      version of the 2018 position paper from the Study Group on Heart and Brain
      Interaction of the Heart Failure Association. It addresses the reciprocal impact
      on HF of several pathological brain conditions, including acute and chronic low
      perfusion of the brain, and impairment of higher cortical and brain stem
      functions. Treatment-related interactions - medical, interventional and device
      related - are also discussed.

PMID- 30206483
TI  - Calming the Nervous Heart: Autonomic Therapies in Heart Failure.
AB  - Heart failure (HF) is associated with significant morbidity and mortality. The
      disease is characterised by autonomic imbalance with increased sympathetic
      activity and withdrawal of parasympathetic activity. Despite the use of medical
      therapies that target, in part, the neurohormonal axis, rates of HF progression,
      morbidity and mortality remain high. Emerging therapies centred on
      neuromodulation of autonomic control of the heart provide an alternative device
      based approach to restoring sympathovagal balance. Preclinical studies have
      proven favourable, while clinical trials have had mixed results. This article
      highlights the importance of understanding structural/functional organisation of
      the cardiac nervous system as mechanistic-based neuromodulation therapies evolve.

PMID- 30206484
TI  - Metabolic Modulation of Cardiac Metabolism in Heart Failure.
AB  - Heart failure (HF) is associated with metabolic changes that cause a progressive
      impairment of cardiac and skeletal muscle high-energy phosphate production. As a
      consequence of the impaired cardiac metabolism, other processes are activated in
      the failing heart that further exacerbate the progression of HF. The reduced
      production of high-energy phosphates has important implications for both systole
      and diastole in HF with both preserved and reduced left ventricular function. The
      aim of this review is to summarise the state-of-the-art on metabolic therapy in
      HF with a particular focus on trimetazidine. Metabolic agents optimise cardiac
      substrate metabolism without exerting negative haemodynamic effects. In
      particular, as studies with metabolic agents modulating cardiac metabolism have
      consistently demonstrated, this approach is effective in improving symptoms,
      functional capacity and prognosis in people with HF when added to optimal medical
      therapy. Therefore, the modulation of cardiac metabolism is an important
      therapeutic approach to the treatment of HF, especially in patients where it is
      of ischaemic or metabolic origin. Although further studies are needed, metabolic
      agents might be a new, effective strategy for the treatment of HF.

PMID- 30206485
TI  - Frailty in Heart Failure: Implications for Management.
AB  - Frailty is a complex clinical syndrome associated with ageing and chronic
      illness, resulting from multiple organ impairment; physiological reserves
      decrease and vulnerability to stressors increase. The role of frailty in
      cardiovascular disease has become increasingly recognised. Up to 79% of patients
      with heart failure are frail. Moreover, frailty is associated with a worse
      quality of life and poor prognosis. This review summarises the available
      literature on frailty in HF and highlights indications for its management.

PMID- 30206486
TI  - Exercise Training in Heart Failure Patients With Persistent Atrial Fibrillation:
      a Practical Approach.
AB  - Persistent AF is present in at least 20 % of patients with chronic heart failure
      (CHF) and is related to a poor prognosis and more severe cardiac arrhythmias. CHF
      and AF share a common pathophysiology and can exacerbate one another. Exercise
      programmes for people with CHF have been shown to improve aerobic capacity,
      prognosis and quality of life. Given that patients with both CHF and AF show
      greater impairment in exercise performance, exercise training programmes have the
      potential to be highly beneficial. Optimal clinical evaluation using a
      cardiopulmonary exercise test should be performed before starting a training
      programme. Heart rate should be calculated over a longer period of time In
      patients with CHF and AF than those in sinus rhythm. The use of telemetry is
      advised to measure HR accurately during training. If telemetry is not available,
      patients can be safely trained based on the concomitant workload. An aerobic
      exercise training programme of moderate to high intensity, whether or not
      combined with strength training, is advised in patients with CHF and AF. Optimal
      training modalities and their intensity require further investigation.

PMID- 30206487
TI  - Postpartum Cardiomyopathy and Considerations for Breastfeeding.
AB  - Postpartum cardiomyopathy (PPCM) is a rare condition that develops near the end
      of pregnancy or in the months after giving birth, manifesting as heart failure
      secondary to left ventricular systolic dysfunction. Clinical progression varies
      considerably, with both end-stage heart failure occurring within days and
      spontaneous recovery seen. Treatment pathways for heart failure are well
      established, but the evidence about the safety of medicines passed to infants
      during breastfeeding is scarce and mainly poor; this often leads to an incorrect
      decision that a mother should not breastfeed. Given its benefits to both mother
      and infant, breastfeeding should not routinely be ruled out if the mother is
      taking heart failure medication but the consequences for the infant need to be
      considered. An informed risk assessment to minimise potential harm to the infant
      can be carried out using the evidence that is available along with a
      consideration of drug properties, adverse effects, paediatric use and
      pharmacokinetics. In most cases, risks can be managed and infants can be
      monitored for potential problems. Breastfeeding can be encouraged in women with
      cardiac dysfunction with PPCM although treatment for the mother takes priority
      with breastfeeding compatibility being the secondary consideration. International
      research is continuing to establish efficacy and safety of pharmacotherapy in
      PPCM.

PMID- 30206488
TI  - Access to safe blood in low-income and middle-income countries: lessons from
      India.
AB  - Timely, affordable access to screened blood is essential to the provision of safe
      surgical care and depends on three key aspects: adequate volume of blood supply,
      safe protocols for blood donation and transfusion, and appropriate regulation to
      ensure safe, equitable and sustainable distribution. Many low-income and middle
      income countries experience a deficit in these categories, particularly in rural
      areas. We draw on the experience of rural surgical practitioners in India and
      summarise the existing literature to evaluate India's blood banking system and
      discuss its major barriers to the safe and equitable provision of blood. Many low
      income and middle-income countries struggle with accruing a sufficient voluntary,
      unpaid blood donation base to meet the need. Efforts to increase blood supply
      through mandatory family replacement donations can lead to dangerous delays in
      care provision. Additionally, prohibition of unbanked, directed blood transfusion
      restricts the options of health practitioners, particularly in rural areas. Blood
      safety is also a significant concern, and efforts must be taken to decrease the
      risk of transfusion-transmitted infections and inform and treat donors who test
      positive. Lastly, blood banking systems need a centralised governing body to
      ensure fair prices for blood, promote comprehensive transfusion reporting and
      increase system-wide transparency and accountability.

PMID- 30206489
TI  - Advances in radiation therapy for thoracic malignancies.

PMID- 30206490
TI  - Advances in the use of motion management and image guidance in radiation therapy
      treatment for lung cancer.
AB  - The development of advanced radiation technologies, including intensity-modulated
      radiation therapy (IMRT), stereotactic body radiation therapy (SBRT) and proton
      therapy, has resulted in increasingly conformal radiation treatments. Recent
      evidence for the importance of minimizing dose to normal critical structures
      including the heart and lungs has led to incorporation of these advanced
      treatment modalities into radiation therapy (RT) for non-small cell lung cancer
      (NSCLC). While such technologies have allowed for improved dose delivery,
      implementation requires improved target accuracy with treatments, placing
      increasing importance on evaluating tumor motion at the time of planning and
      verifying tumor position at the time of treatment. In this review article, we
      describe issues and updates related both to motion management and image guidance
      in the treatment of NSCLC.

PMID- 30206492
TI  - Optimizing radiation dose and fractionation for the definitive treatment of
      locally advanced non-small cell lung cancer.
AB  - Radiation therapy is the foundation for treatment of locally advanced non-small
      cell lung cancer (NSCLC), a disease that is often inoperable and has limited long
      term survival. Local control of disease is strongly linked to patient survival
      and continues to be problematic despite continued attempts at changing the dose
      and fractionation of radiation delivered. Technological advancements such as 4
      dimensional computed tomography (CT) based planning, positron emission tomography
      (PET) based target delineation, and daily image guidance have allowed for ever
      more accurate and conformal treatments. A limit to dose escalation with
      conventional fractions of 2 Gy once per day appears to have been reached at 60 Gy
      in the randomized trial Radiation Therapy Oncology Group (RTOG) 0617. Higher
      doses were surprisingly associated with worse overall survival. Approaches other
      than conventional dose escalation have been explored to better control disease
      including accelerating treatment to limit tumor repopulation both with
      hyperfractionation and its multiple small (<2 Gy) fractions each day and with
      hypofractionation and its single larger (>2 Gy) fraction each day. These
      accelerated regimens are increasingly being used with concurrent chemotherapy,
      and multiple institutions have reported it as tolerable. Tailoring treatment to
      individual patient disease and normal anatomic characteristics has been explored
      with isotoxic dose escalation up to the tolerance of organs at risk, with both
      hyperfractionation and hypofractionation. Metabolic imaging during and after
      treatment is increasingly being used to boost doses to residual disease. Boost
      doses have included moderate hypofractionation of 2-4 Gy, and more recently
      extreme hypofractionation with stereotactic body radiation therapy (SBRT). In
      spite of all these changes in dose and fractionation, lung and cardiovascular
      toxicity remain obstacles that limit disease control and patient survival.

PMID- 30206491
TI  - Stereotactic body radiation therapy (SBRT) for early stage non-small cell lung
      cancer (NSCLC): contemporary insights and advances.
AB  - The standard-of-care treatment for early-stage non-small cell lung cancer (NSCLC)
      continues to be surgery in the form of lobectomy or pneumonectomy. Stereotactic
      body radiation therapy (SBRT) has evolved as a viable alternative to surgery for
      medically inoperable patients, achieving excellent local control (LC) with
      relatively minimal toxicity in standard-risk patients. Nevertheless, the
      maturation of SBRT has fostered debate regarding its use, technique, dose, and
      fractionation, particularly in the context of patient- and disease-specific
      characteristics such as tumor size and location. This review will cover the
      recent trends and future directions of SBRT as it becomes an increasingly
      individualized modality in the treatment of early-stage NSCLC.

PMID- 30206493
TI  - Advanced radiation techniques for locally advanced non-small cell lung cancer:
      intensity-modulated radiation therapy and proton therapy.
AB  - Radiation therapy (RT) represents an integral part of a multimodality treatment
      plan in the definitive, preoperative and postoperative management of non-small
      cell lung cancer (NSCLC). Technological advances in RT have enabled a shift from
      two-dimensional radiotherapy to more conformal techniques. Three-dimensional
      conformal radiotherapy (3DCRT), the current minimum technological standard for
      treating NSCLC, allows for more accurate delineation of tumor burden by using
      computed tomography-based treatment planning instead of two-dimensional
      radiographs. Intensity-modulated RT (IMRT) and proton therapy represent
      advancements over 3DCRT that aim to improve the conformity of RT and provide the
      possibility for dose escalation to the tumor by minimizing radiation dose to
      organs at risk. Both techniques likely confer benefits to certain anatomic
      subgroups of NSCLC requiring RT. This article reviews pertinent studies
      evaluating the use of IMRT and proton therapy in locally advanced NSCLC, and
      outlines challenges, indications for use, and areas for future research.

PMID- 30206494
TI  - Combining immunotherapy with radiation therapy in thoracic oncology.
AB  - Thoracic malignancies comprise some of the most common and deadly cancers.
      Immunotherapies have been proven to improve survival outcomes for patients with
      advanced non-small cell lung cancer (NSCLC) and show great potential for patients
      with other thoracic malignancies. Radiation therapy (RT), an established and
      effective treatment for thoracic cancers, has acted synergistically with
      immunotherapies in preclinical studies. Ongoing clinical trials are exploring the
      clinical benefits of combining RT with immunotherapies and the optimal manner in
      which to deliver these complementary treatments.

PMID- 30206497
TI  - The current state of oligometastatic and oligoprogressive non-small cell lung
      cancer.
AB  - Oligometastatic disease is defined as an intermediate state between localized and
      widespread metastatic disease. Given that in the oligometastatic state gross
      tumors represent the full extent of disease, there may be a role for curative
      local therapy despite metastatic disease. As nearly 60% of patients with non
      small cell lung cancer (NSCLC) present with metastatic disease and another 45% of
      patients with initially localized disease will ultimately develop distant
      metastases, NSCLC represents a prime disease for aggressive intervention. In this
      review, the definition, prognostic factors, patient selection, rationale and
      evidence for treatment of oligoprogressive and oligometastatic NSCLC is
      discussed, including recent prospective trials and future directions.

PMID- 30206496
TI  - Reirradiation for locoregionally recurrent non-small cell lung cancer.
AB  - Locoregional failure in non-small cell lung cancer (NSCLC) remains high, and the
      management for recurrent disease in the setting of prior radiotherapy is
      difficult. Retreatment options such as surgery or systemic therapy are typically
      limited or frequently result in suboptimal outcomes. Reirradiation (reRT) of
      thoracic malignancies may be an optimal strategy for providing definitive local
      control and offering a new chance of cure. Yet, retreatment with radiation
      therapy can be challenging for fear of excessive toxicities and the inability to
      safely deliver definitive (>=60 Gy) doses of reRT. However, with recent
      improvements in radiation delivery techniques and image-guidance, dose-escalation
      with reRT is possible and outcomes are encouraging. Here, we present a review of
      various radiation techniques, clinical outcomes and associated toxicities in
      patients with locoregionally recurrent NSCLC treated primarily with reRT.

PMID- 30206495
TI  - The developing role of FDG PET imaging for prognostication and radiotherapy
      target volume delineation in non-small cell lung cancer.
AB  - Advancements in functional imaging technology have allowed new possibilities in
      contouring of target volumes, monitoring therapy, and predicting treatment
      outcome in non-small cell lung cancer (NSCLC). Consequently, the role of 18F
      fluorodeoxyglucose positron emission tomography (FDG PET) has expanded in the
      last decades from a stand-alone diagnostic tool to a versatile instrument
      integrated with computed tomography (CT), with a prominent role in lung cancer
      radiotherapy. This review outlines the most recent literature on developments in
      FDG PET imaging for prognostication and radiotherapy target volume delineation
      (TVD) in NSCLC. We also describe the challenges facing the clinical
      implementation of these developments and present new ideas for future research.

PMID- 30206499
TI  - The expanding role of radiation therapy for thymic malignancies.
AB  - The role of radiation therapy (RT) in thymic malignancies has long been subject
      to considerable controversy. The main role for RT is in the setting of adjuvant
      therapy after surgical tumor resection, especially in advanced or incompletely
      resected cases. However, recent studies with larger patient numbers and cleaner
      study populations than previous studies have indicated a potentially clearer than
      previously assumed benefit after post-operative RT (PORT) even for completely
      resected patients with earlier stages of thymoma. In marginally resectable
      patients RT may be used in combination with neoadjuvant chemotherapy to shrink
      tumors and thereby potentially enable resection. In unresectable patients
      concurrent or sequential chemotherapy and RT can be employed as the definitive
      nonsurgical approach. The tendency of thymic tumors to recur in the pleural space
      highlights the necessity for more effective approaches to identify and treat high
      risk patients. Experiences in other pleural malignancies may pave the way to
      novel treatment modalities, for example pleural IMRT. The role of these
      techniques in thymic malignancies has yet to be determined and is not advisable
      at the current time outside of a clinical study. As the disease often takes an
      indolent course with excellent long-term local control (LC) and survival, late
      toxicities related to radiation of the mediastinum and adjacent organs at risk
      (OARs) have to be taken into consideration and may jeopardize the benefit
      patients experience from RT, especially in younger patients with a long
      anticipated life expectancy. Radiation techniques, such as intensity modulated RT
      (IMRT) and proton beam therapy (PBT), have substantially reduced the exposure of
      OARs to ionizing radiation which is expected to translate into reduced long-term
      toxicities. Hence, the risk-benefit ratio of RT in early stage thymoma patients
      may be shifted favorably.

PMID- 30206498
TI  - The evolving role of radiotherapy in the management of small cell lung cancer.
AB  - Small cell lung cancer (SCLC) represents a small but significant subset of newly
      diagnosed lung cancers. In spite of being both chemo- and radiation-sensitive,
      SCLC has a high-propensity for recurrence after treatment. Although systemic
      therapy plays a central role in the management of patients with SCLC, many of the
      advances in overall survival for patients with SCLC have directly related to the
      use of radiation therapy. The objective of this review is to discuss the key
      radiation therapy clinical trials that have defined the current standard-of-care
      treatment for SCLC, and to review ongoing advances in radiation therapy that may
      further advance outcomes for patients with SCLC.

PMID- 30206500
TI  - Adjuvant, neoadjuvant, and definitive radiation therapy for malignant pleural
      mesothelioma.
AB  - While ionizing radiotherapy (RT) can provide durable local control, the relative
      radiosensitivity of surrounding organs such as the lungs and heart and the
      distributed nature of the pleura limit the ability to safely deliver RT for
      patients with malignant pleural mesothelioma (MPM). Recent advances in the
      technological sophistication of RT planning and delivery devices have resulted in
      increased spatial control of irradiation dose that has extended the palliative
      and definitive applications of RT for patients with MPM. This review will outline
      the logistical, mechanistic and clinical basics of RT and the clinical trials
      supporting the use of RT in the multidisciplinary care of patients with MPM.

PMID- 30206501
TI  - The future of accreditation of continuing medical education (CME)-continuing
      professional development (CPD) in Europe: harmonisation through dialogue and
      consensus.
AB  - In Europe, there are currently some 30 different jurisdictions and no overarching
      legislation regarding CME-CPD accreditation, since legislative competency related
      to national health-care systems lies with national authorities. Thus, public
      demonstration of professional agreement regarding the principles, rules and
      practice of CME-CPD as well as its accreditation is a highly desirable
      professional and political objective in Europe, where free movement and freedom
      to offer professional (medical) services is a key feature of the EU vision of the
      single market. The newly formed association of independent European accreditors,
      Continuing Medical Education - European Accreditors (CME-EA) is committed to
      offering a platform for dialogue between individuals and organisations involved
      in definition of professional codes in general, and accreditation of CME-CPD in
      particular on the national level. The aim is to reach a European consensus on
      principles and rules applied in planning and delivery of CME-CPD. This includes
      consensus on constituent characteristics of accreditors as well as principles and
      practice of accreditation.

PMID- 30206503
TI  - Coadministration of intramuscular olanzapine and benzodiazepines in agitated
      patients with mental illness.
AB  - Introduction: Intramuscular antipsychotics are commonly used to manage agitated
      patients. In 2005, Eli Lilly placed a warning on olanzapine's prescribing
      information following post-marketing reports of fatal drug reactions when
      intramuscular olanzapine was used in the setting of benzodiazepines. Data is
      lacking examining this drug combination. Methods: A medication use evaluation was
      conducted at a county psychiatric hospital surveying the usage of concomitant
      intramuscular olanzapine and lorazepam from October 1, 2016, to July 20, 2017. A
      literature search was conducted to review available evidence. Results: Ninety-one
      instances of the drug combination were discovered, with no serious adverse events
      following administration. Of these 91 patients, 41 received both medications
      within 60 minutes of each other. No instances of hypotension, bradycardia,
      bradypnea, or oxygen desaturation occurred following administration. The
      literature review yielded 1 randomized, placebo-controlled clinical trial, 3
      retrospective chart reviews, and several case studies. Discussion: Data detailing
      a causal relationship between olanzapine/benzodiazepine combinations and serious
      adverse effects is lacking. Available evidence does not consistently support a
      strong cause and effect relationship. The results of this medication use
      evaluation are not consistent with the Food and Drug Administration warning.
      Further controlled research is needed to help define the actual risk of using
      concomitant intramuscular olanzapine and benzodiazepines.

PMID- 30206502
TI  - Extent of use of long-acting injectable antipsychotics in children and
      adolescents within Indiana Medicaid.
AB  - Introduction: Oral formulations of the antipsychotics aripiprazole, asenapine,
      lurasidone, olanzapine, paliperidone, quetiapine, and risperidone are indicated
      for use in pediatrics for several diagnoses. Long-acting injectable (LAI)
      antipsychotics are of interest in this special population because they may be
      used due to convenience and desire to improve adherence, despite limited support
      in the literature. The primary intent of this study is to provide descriptive
      information on the use of paliperidone palmitate, risperidone microspheres,
      aripiprazole extended-release injection, and olanzapine pamoate in pediatric
      patients within Indiana Medicaid. Methods: This study was a retrospective
      database analysis, which retrieved information from Indiana Medicaid over a 2
      year timeframe spanning from July 1, 2012, through June 30, 2014. The study
      included the prescription medications filled for all children and adolescents
      within Indiana Medicaid who received the LAI antipsychotics paliperidone
      palmitate, risperidone microspheres, aripiprazole extended-release injection, and
      olanzapine pamoate. Results: From July 1, 2012, through June 30, 2014, 150
      Indiana Medicaid patients younger than 18 years old were prescribed a LAI
      atypical antipsychotic. A total of 1013 LAI atypical antipsychotic doses were
      billed to Indiana Medicaid during the study period for pediatric patients.
      Paliperidone palmitate was billed most frequently. Discussion: Long-acting
      injectable atypical antipsychotics are being prescribed for children and
      adolescents within Indiana Medicaid, despite minimal clinical evidence supporting
      use. There is a need for further research in this area to increase
      generalizability of results and aid in implementation of policies to prevent
      inappropriate use of LAI antipsychotics in children and adolescents.

PMID- 30206504
TI  - Self-stigma of antidepressant users through secondary analysis of PhotoVoice
      data.
AB  - Introduction: Aspects of self-stigma and medication-related stigma among
      individuals with depressive disorders remain largely unexplored. The primary
      objective of this study is to highlight and characterize self-stigma and
      medication-related stigma experiences of antidepressant users. Methods: This is a
      secondary analysis of data obtained from PhotoVoice studies examining
      psychotropic medication experiences. Transcripts of reflections from 12
      individuals self-reporting a depressive disorder diagnosis and receipt of a
      prescription for an antidepressant were included. A directed content analysis
      approach based on expansion of the Self-Stigma of Depression Scale and an
      iterative process of identification of medication-stigma and stigma-resistance
      were used. Total mentions of self-stigma, stigma resistance, medication stigma,
      and underlying themes were tallied and evaluated. Results: Self-stigma was
      mentioned a total of 100 times with at least 2 mentions per participant. Self
      blame was the most prominent construct of self-stigma and was mentioned nearly
      twice as often as any other self-stigma construct. Most participants also made
      mentions of self-stigma resistance. Half of the individual participants mentioned
      stigma resistance more times than they mentioned self-stigma, which suggests some
      surmounting of self-stigma. Medication-related stigma was also prominent,
      denoting negativity about the presence of medications in one's life. Discussion:
      Self-stigma related to self-blame may be problematic for antidepressant users.
      Identification and measurement of stigma resistance, especially in peer
      interactions, may represent a promising concept in overcoming self-stigma. Future
      work should explore emphasizing self-blame aspects when designing interventions
      to reduce self-stigma among individuals with depressive disorders and explore
      development of tools to measure stigma resistance.

PMID- 30206505
TI  - Changing student attitudes and perceptions toward opioid use disorder.
AB  - Introduction: With the opioid epidemic creating a group of patients with unique
      health care needs, pharmacists have an opportunity to be a good resource for
      patients recovering from opioid use disorder (OUD). To accomplish this, it is
      essential that pharmacists are knowledgeable and unbiased toward this patient
      population. Methods: Because the curriculum in place to obtain a PharmD at Drake
      University does not include in-depth information on substance use disorders,
      study investigators offered students an opportunity to receive more intensive
      education. Faculty members at Drake University provided didactic and panel
      discussion presentations on topics such as opioid pharmacology, OUD, and
      treatment options. The students were assessed for their perception of knowledge
      and stigma before and after the summit by using a 5-point Likert scale to measure
      their attitudes toward 10 statements. Results: Total knowledge scores showed a
      significant change of 3.1, indicating an increase in perceived understanding of
      materials presented (P < .0001). Total stigma scores also changed by 1.4,
      illustrating a statistically significant decrease in negative perceptions (P =
      .0198). Discussion: By providing more in-depth education, the summit showed that
      increasing pharmacy student knowledge about OUD and its treatment may decrease
      associated stigma.

PMID- 30206506
TI  - Evaluation of perceptions and knowledge of mental illness in the United States
      through crowdsourcing.
AB  - Introduction: Crowdsourcing is a method of data collection with possible benefits
      in assessing perceptions of mental illness in a large US population. Methods: The
      objective was to describe perceptions and trends of stigma surrounding mental
      illness in the United States using crowdsourcing. An online survey was conducted
      evaluating adults in the United States recruited via the online resource Amazon
      Mechanical Turk. Questions evaluated demographics and perceptions of mental
      illness. Survey data were adjusted for demographic variables and compared via
      logistic regression. Results: Respondents (n = 1422) were predominately 18 to 30
      years of age (n = 743; 52.3%) and white (n = 1101; 77.4%). Over half reported an
      individual close to them had mental illness (n = 932; 65.5%), and more than one
      quarter (n = 397; 27.9%) reported having a current or previous mental illness.
      Non-whites were less likely to agree that: medications are effective (odds ratio
      [OR] 0.63); they would be comfortable around a coworker with mental illness (OR
      0.66); and mental illness is inheritable (OR 0.74). They are also more likely to
      agree that mental illness is preventable (OR 1.49). Individuals reporting mental
      illness were more likely to agree that medications (OR 1.34; 95% confidence
      interval 1.03 to 1.74) and talk therapy (OR 1.46; 95% confidence interval 1.12 to
      1.90) are effective. Those reporting some or no college were more likely to agree
      that the United States has good access to mental health treatment. Discussion:
      Crowdsourcing may be an effective way to obtain information regarding
      demographics, stigma, and mental illness. Personal experiences with mental
      illness, ethnicity, and educational level appear to continue to impact
      perceptions of mental illness.

PMID- 30206508
TI  - Ziconotide-induced psychosis: A case report and literature review.
AB  - Ziconotide is an intrathecally administered medication indicated for the
      treatment of severe chronic pain in patients who are intolerant of or refractory
      to other treatment options. A black box warning is included in the packaging and
      states ziconotide is contraindicated in patients with a preexisting history of
      psychosis. Patients taking ziconotide should be monitored for evidence of
      cognitive impairment, hallucinations, or changes in mood, and ziconotide should
      be discontinued if neurological or psychiatric signs and symptoms appear. We
      present a case of a 49-year-old white male with no previous neuropsychiatric
      history who received ziconotide for several years before he developed command
      auditory hallucinations within 24 hours of a dose increase. Upon admission to the
      emergency room, the patient's pain management physician was contacted and the
      ziconotide dose was decreased and eventually discontinued. Because of a
      continuation of symptoms, the patient was transferred from the emergency room to
      an acute care psychiatric hospital where he was started on risperidone 1 mg
      orally at bedtime. At discharge, the patient was noted to be in good behavioral
      control without any hallucinations. The patient was encouraged to follow up with
      his pain management physician to determine if ziconotide should be reconsidered.

PMID- 30206507
TI  - Overview of pharmacogenomic testing in clinical practice.
AB  - Introduction: Pharmacogenomic tests relevant to neuropsychiatric medications have
      been clinically available for more than a decade, but the utility of regular
      testing is still unknown. Tests available include both pharmacokinetic and
      pharmacodynamic targets. The potential practice benefits vary with each target.
      Methods: A 10-year literature review was completed utilizing the PubMed database
      to identify articles relating to the specific pharmacogenomic targets discussed.
      Further article selection was based on author review for clinical utility.
      Results: The clinical dosing guidance available for neuropsychiatric medications
      such as selective serotonin reuptake inhibitors and tricyclic antidepressants
      with varying genotypes is useful and has strong evidence to support testing, but
      it is limited to mainly pharmacokinetic application. Pharmacodynamic targets are
      gaining additional evidence with increased research, and although the mechanisms
      behind the potential interactions are scientifically sound, the bridge to
      clinical practice application is still lacking. Discussion: Although the benefits
      of decreasing adverse reactions and improving response time are appealing,
      clinicians may not utilize pharmacogenomic testing in routine practice due to
      several barriers. Further clinical guidance and studies are needed to support
      testing for other neuropsychiatric medications and targets.

PMID- 30206509
TI  - Rechallenge of lamotrigine after development of rash.
AB  - Lamotrigine (LTG) is associated with the potential for a life-threatening rash
      (eg, Stevens-Johnson syndrome or toxic epidermal necrolysis). The incidence has
      been linked to rapid titration and an interaction with valproic acid that can
      increase the level of LTG. Providers often have difficulty discriminating between
      serious versus benign rashes, and the package insert recommends discontinuing the
      medication at the first sign of a rash. Therefore, many patients end up being
      taken off LTG when it may have been effective for them. We present a case where
      LTG is reintroduced with a faster initial titration than what is noted in the
      literature after development of a rash. This case is also unique in that the
      patient had been on LTG for years prior to emergence of the rash and demonstrates
      that retrials can be successful.

PMID- 30206510
TI  - Utilization of G-CSF and GM-CSF as an alternative to discontinuation in clozapine
      induced neutropenia or leukopenia: A case report and discussion.
AB  - Clozapine remains the definitive gold standard for treatment-resistant
      schizophrenia despite limitations in use because of hematological abnormalities.
      Neutropenia or leukopenia are often treated with interruption of clozapine
      treatment, frequently resulting in clinical decompensation, hospitalization,
      increased burden to patient care, and increased risk of suicide. Colony
      stimulating factors, including granulocyte colony-stimulating factors and
      granulocyte-macrophage colony-stimulating factors, are cytokines that stimulate
      proliferation and differentiation of myeloid precursor cells. Their use in the
      prevention and treatment of clozapine-associated neutropenia presents an
      alternative to clozapine discontinuation in certain cases. We present a case
      report of successful periodic granulocyte-macrophage colony-stimulating factor
      use with clozapine in a patient with treatment-resistant schizophrenia, as well
      as discussion of a practical approach to patients with possible clozapine-induced
      neutropenia or leukopenia.

PMID- 30206511
TI  - Hypercalcemia-induced acute kidney injury in a Caucasian female due to
      radiographically silent systemic sarcoidosis.
AB  - . Sarcoidosis is a rare autoimmune disease resulting in formation of non
      necrotizing "non-caseating" granulomas generally in the lung. The disease
      classically strikes African American females in their fourth and fifth decades.
      The resulting hypercalcemia is a result of 1-alpha hydroxylase overexpression in
      granulomas with increased 1,25-dihydroxy vitamin D levels. This phenomenon can
      also be observed in mycobacterial and fungal infections that produce granulomas
      in infected patients. Thus, chronic infectious diseases are part of differential
      diagnosis of granulomatous processes. We present an elderly Caucasian female who
      presented with hypercalcemia with serum calcium of 11 - 14 mg/dL and an elevated
      ionized calcium of 1.4 - 1.5 mmol/L. Initially cholecalciferol supplements were
      stopped, but hypercalcemia persisted for more than 2 months. 1,25-dihydroxy
      vitamin D levels were markedly elevated with low normal 25-hydroxy vitamin D
      levels, angiotensin-converting enzyme levels were also high, and chest computed
      tomography (CT) imaging was negative for any lymphadenopathy (including perihilar
      lymphadenopathy). Malignancy and infectious workups were negative for fungal and
      mycobacterial infections. Positron emission tomography revealed several small
      lymph nodes in right upper lobe of lung, and biopsy of bone marrow and lung lymph
      nodes revealed non-caseating granulomata. We present an atypical case of occult
      sarcoidosis presenting mainly with biochemical findings without any definitive
      imaging findings, making diagnosis a clinical challenge.

PMID- 30206512
TI  - Evaluation of the implementation of an internet intervention in well-baby
      clinics: A pilot study.
AB  - Purpose: Despite promising results, internet interventions are not widely
      accessible or well-integrated in health services. The objective of this study
      was, therefore, to examine the implementation of an internet intervention ('Mamma
      Mia') for the prevention of perinatal depression in Norwegian well-baby clinics
      (i.e., primary care). Methods: Mamma Mia begins in mid-pregnancy and lasts up to
      6 months after childbirth. It consists of 44 online sessions, supported by
      midwives and public health nurses at up to 5 contact points during this period,
      following principles of empathic communication. Well-baby clinics offer free,
      universal services to all pregnant women and children aged 0 to 5 years in Norway
      and were recruited via an intermediary organization for this study. Data were
      collected at pre- and post-training, but before the delivery of Mamma Mia in
      clinics, and at 3 and 6 months follow-up. Quantitative and qualitative data were
      used to evaluate the training in Mamma Mia, examine program implementation (i.e.,
      number of pregnant women registered for the program), and identify barriers and
      enablers of implementation. Results: Twenty-four self-selected healthcare
      professionals from 14 well-baby clinics were recruited, for this study. Training
      increased participants' knowledge about Mamma Mia and exceeded their
      expectations. The program review and implementation plan were necessary training
      components. Implementation climate was related to the number of colleagues
      working with Mamma Mia and overall satisfaction with implementation, while
      characteristics of the intervention predicted the number of registered women at 6
      months. Organizational re-structuring, leadership, and competing activities were
      identified as barriers to implementation that need to be considered further.
      Conclusions: The dissemination and implementation of a health-service supported
      internet intervention appears to be promising but requires further research.

PMID- 30206513
TI  - Acceptability of internet-based interventions for depression in Indonesia.
AB  - Background: In Indonesia, internet-based interventions may represent a promising
      strategy to reduce the mental health gap given that the level of internet usage
      in the country continues to increase. To check the acceptability of internet
      based interventions, this study investigates factors that contribute to the use
      of internet-based interventions for depression in Indonesia. Method: The survey
      was conducted online and had 904 participants recruited from specific social
      networks on mental health and general social media (Mean age = 27.07, 50.22%
      females). The three dependent variables were (1) behavioral intention to start
      using internet-based interventions for depression, (2) preference to use it as a
      substitute for regular treatments and (3) preference to use it to complement
      regular treatments. The predictor variables included sociodemographic
      characteristics, perceived mental health conditions, personal situational
      characteristics, personal innovativeness toward online services, and depression
      level. Results: A large majority reported to be open to using internet-based
      interventions for depression (73.7%), as well as to use it as a substitution
      (73.3%) or as a complementary (73%) to regular treatments. Personal
      innovativeness toward online services was the strongest significant predictor for
      all types of use, even when corrected for current depression level. When added to
      the analyses separately, depression level was the second strongest predictive
      factor for all dependent variables. Conclusion: The majority of Indonesians
      showed openness to use internet-based interventions for depression. To increase
      the adoption of internet-based interventions for depression, it is important to
      first promote internet usage to more people across the country, especially for
      those who are currently depressed.

PMID- 30206514
TI  - Smartphone-based safety planning and self-monitoring for suicidal patients:
      Rationale and study protocol of the CASPAR (Continuous Assessment for Suicide
      Prevention And Research) study.
AB  - Background: It remains difficult to predict and prevent suicidal behaviour,
      despite growing understanding of the aetiology of suicidality. Clinical
      guidelines recommend that health care professionals develop a safety plan in
      collaboration with their high-risk patients, to lower the imminent risk of
      suicidal behaviour. Mobile health applications provide new opportunities for
      safety planning, and enable daily self-monitoring of suicide-related symptoms
      that may enhance safety planning. This paper presents the rationale and protocol
      of the Continuous Assessment for Suicide Prevention And Research (CASPAR) study.
      The aim of the study is two-fold: to evaluate the feasibility of mobile safety
      planning and daily mobile self-monitoring in routine care treatment for suicidal
      patients, and to conduct fundamental research on suicidal processes. Methods: The
      study is an adaptive single cohort design among 80 adult outpatients or day-care
      patients, with the main diagnosis of major depressive disorder or dysthymia, who
      have an increased risk for suicidal behaviours. There are three measurement
      points, at baseline, at 1 and 3 months after baseline. Patients are instructed to
      use their mobile safety plan when necessary and monitor their suicidal symptoms
      daily. Both these apps will be used in treatment with their clinician.
      Conclusion: The results from this study will provide insight into the feasibility
      of mobile safety planning and self-monitoring in treatment of suicidal patients.
      Furthermore, knowledge of the suicidal process will be enhanced, especially
      regarding the transition from suicidal ideation to behaviour.The study protocol
      is currently under revision for medical ethics approval by the medical ethics
      board of the Vrije Universiteit Medical centre Amsterdam (METc number
      2017.512/NL62795.029.17).

PMID- 30206515
TI  - The effectiveness of guided internet-based cognitive behavioral therapy for
      social anxiety disorder in a routine care setting.
AB  - Social anxiety disorder (SAD) is a common mental disorder with high persistence
      when untreated. As access to effective treatment is limited, guided internet
      based cognitive behavioral therapy (ICBT) has been proposed as an effective
      alternative to face-to-face treatment. In this study, we examined the
      effectiveness of a 14-week therapist-guided ICBT program for patients with SAD
      undergoing routine care. From 2014 to 2017, 169 patients were included in the
      study, of which 145 started the treatment. The sample was all general
      practitioner-referred and had a lower educational level and higher rate of work
      absence compared to similar effectiveness studies. Regarding social anxiety
      symptoms, we identified significant within-group effect sizes (post-treatment: d
      = 1.00-1.10; six-month follow-up: d = 1.03-1.55). We also found significant
      effects on secondary depression symptoms (d = 0.67). Clinically significant
      improvement was reported by 66.2% of the participants, and 16.6% had a
      significant deterioration. Clinical implications of the current study are that
      guided ICBT for SAD is an effective treatment for the majority of the patients
      undergoing routine care. Future studies should explore interventions targeting
      non-responders and deteriorated patients.

PMID- 30206516
TI  - Links between Adolescents' Deep and Surface Learning Approaches, Problematic
      Internet Use, and Fear of Missing Out (FoMO).
AB  - This study was aimed at exploring links between adolescents' deep and surface
      approaches to learning, Fear of Missing Out (FoMO), and Problematic Internet Use
      (PIU) by using Partial Least Squares Structural Equation Modeling (PLS-SEM). The
      analysis corroborated the postulated positive links between surface learning,
      FoMO, and PIU. Moreover, the FoMO construct represented a complimentary mediation
      between the surface learning approach and PIU constructs. This study may lead to
      a plausible inference according to which both FoMO and surface learning share a
      common core characteristic of decreased levels of self-regulation that might lead
      to PIU. Having students acquire and practice skills of self-regulation might help
      them control their levels of FoMO, and consequently their PIU at schools or out
      of-school learning environments.

PMID- 30206517
TI  - Corrigendum to "a pilot randomized controlled trial of E-care 4 caregivers: An
      internet intervention for caregivers of depressed patients" [internet Interv. 9
      (2017) 88-99].
AB  - [This corrects the article DOI: 10.1016/j.invent.2017.06.003.].

PMID- 30206518
TI  - Online mindfulness-enhanced cognitive behavioural therapy for anxiety and
      depression: Outcomes of a pilot trial.
AB  - Transdiagnostic internet-delivered cognitive behavioural therapies (iCBT) are
      effective for treating anxiety and depression, but there is room for improvement.
      In this study we developed a new Mindfulness-Enhanced iCBT intervention by
      incorporating formal and informal mindfulness exercises within an existing
      transdiagnostic iCBT program for mixed depression and anxiety. We examined the
      acceptability, feasibility, and outcomes of this new program in a sample of 22
      adults with anxiety disorders and/or major depression. Participants took part in
      the 7-lesson clinician-guided online intervention over 14 weeks, and completed
      measures of distress (K-10), anxiety (GAD-7), depression (PHQ-9), mindfulness
      (FFMQ) and well-being (WEMBWS) at pre-, mid-, post-treatment, and three months
      post-treatment. Treatment engagement, satisfaction, and side-effects were
      assessed. We found large, significant reductions in distress (Hedges g = 1.55),
      anxiety (g = 1.39), and depression (g = 1.96), and improvements in trait
      mindfulness (g = 0.98) and well-being (g = 1.26) between baseline and post
      treatment, all of which were maintained at follow-up. Treatment satisfaction was
      high for treatment-completers, with minimal side-effects reported, although
      adherence was lower than expected (59.1% completed). These findings show that it
      is feasible to integrate online mindfulness training with iCBT for the treatment
      of anxiety and depression, but further research is needed to improve adherence. A
      randomised controlled trial is needed to explore the efficacy of this program.

PMID- 30206520
TI  - The acceptability of an online intervention using positive psychology for
      depression: A qualitative study.
AB  - Background: Positive psychology interventions may usefully treat depression and
      can be delivered online to reduce the treatment gap. However, little is known
      about how acceptable patients find this approach. To address this, the present
      study interviewed recent users of a positive psychology self-help website.
      Methods: In-depth semi-structured interviews explored the experiences of twenty
      three participants from a larger feasibility study. A stratified purposive
      sampling strategy selected participants with varying intervention experience
      according to their intervention logins, as well as varying age, gender and
      depressive symptoms. Framework analysis was used to explore patterns and linkages
      within and between participants' accounts. Results: Acceptability varied between
      participants. Those who found it more acceptable felt it was relevant to their
      depression and reported feeling empowered by a self-help approach. Conversely,
      participants for whom it was less acceptable perceived the positive focus
      irrelevant to their depression and found the emphasis on self-action
      unsupportive. Conclusions: The acceptability of an online positive psychology
      intervention may be facilitated by a patients' preference for a psychological
      focus on the positive. However, patients may also have distinct preferences for
      online self-help. Future research should investigate the importance of the
      therapeutic orientation of online self-help interventions and whether patients'
      preferences for these can be reliably identified. This could help to target
      online self-help in clinical practice.

PMID- 30206519
TI  - A systematic review on the implementation of eHealth interventions for informal
      caregivers of people with dementia.
AB  - Objectives: The objectives were to (1) systematically review the literature on
      the implementation of eHealth interventions for informal caregivers of people
      with dementia, and (2) identify determinants of successful implementation.
      Methods: Online databases were searched for articles about eHealth interventions
      for informal caregivers of people with dementia, providing information on their
      implementation. Articles were independently screened and inductively analyzed
      using qualitative analysis. The analysis was mapped onto the Consolidated
      Framework for Implementation Research (CFIR; Damschroder et al., 2009). Findings:
      46 articles containing 204 statements on implementation were included. The
      statements on implementation were grouped into four categories: Determinants
      associated with the eHealth application, informal caregiver, implementing
      organization, or wider context. Mapping of the determinants on the CFIR revealed
      that studies have focused mostly on characteristics of the intervention and
      informal caregiver. Limited attention has been paid to organizational
      determinants and the wider context. Conclusions: Despite prolific effectiveness
      and efficacy research on eHealth interventions for caregivers of people with
      dementia, there is a critical dearth of implementation research. Furthermore,
      there is a mismatch between eHealth intervention research and implementation
      frameworks, especially concerning organizational factors and wider context. This
      review underscores the importance of future implementation research in bridging
      the gap between research and practice.

PMID- 30206521
TI  - Treatment engagement in an internet-delivered cognitive behavioral program for
      pediatric chronic pain.
AB  - Internet-delivered cognitive-behavioral therapy (iCBT) is a promising treatment
      for chronic pain among youth, but effect sizes are small, and strategies aimed at
      enhancing treatment effects are needed. Participants' engagement with the program
      may be an important factor in determining treatment outcomes. The primary aim of
      the current study was to examine the relationship between treatment engagement
      and treatment outcomes. Secondarily, we sought to characterize participant
      engagement in an iCBT program for adolescents with chronic pain and their
      parents. Participants included 134 adolescents randomized to the intervention arm
      of a controlled trial examining iCBT for chronic pain. Overall engagement with
      the intervention by adolescents and parents was high. Parental engagement (number
      of modules completed by parents and number of parent logins) predicted adolescent
      activity limitations change scores at post-treatment. Contrary to our
      expectation, adolescent treatment engagement was not predictive of treatment
      outcomes. Results indicate that parental engagement with the program may be an
      important predictor of treatment outcomes. Further research is needed to better
      understand influences of treatment engagement on outcomes in iCBT for youth.

PMID- 30206522
TI  - Evaluation of a brief unguided psychological online intervention for depression:
      A controlled trial including exploratory moderator analyses.
AB  - Background: Psychological online interventions (POIs) reduce depression but we
      know little about factors influencing their effectiveness. We evaluated a new,
      brief POI for depression and conducted exploratory moderator analyses. Methods:
      In this online trial (German Clinical Trials Register; DRKS00011045), we
      allocated participants to treatment as usual (TAU; n = 67) or POI (n = 65). At
      first, we randomized participants; later we allocated participants based on
      depression severity in order to counter baseline differences. The unguided POI
      addressed behavioral activation and depressive thinking in a single module with
      25 webpages (including a smartphone application). We did one assessment at
      baseline and a post-assessment four weeks later. Results: At post-assessment,
      depression (p = .586), behavioral activation (p = .332), and dysfunctional
      attitudes (p = .499) did not differ between groups. When concurrent treatments
      (medication/psychotherapy) remained constant/decreased, the POI outperformed TAU
      (p = .031). POI-participants with lower willingness to change (p = .030) or
      higher education (p = .017) were less likely to worsen (i.e., experience
      increased depressive symptoms) compared to TAU. Discussion: The targeted sample
      size was not reached, measurements were self-reported, and randomization failed.
      The POI's content may have been too limited. Concurrent treatments, which were
      more often sought out by TAU participants, diminished group differences and
      should be considered in future studies. Brief POIs may protect against worsening
      of depressive symptoms among highly educated participants or those with low
      willingness to change.

PMID- 30206524
TI  - The rate of reply and nature of responses to suicide-related posts on Twitter.
AB  - The social media platform Twitter has been used by individuals to communicate
      suicidal thoughts and intentions. Currently, the nature and rate of reply to this
      type of Twitter content is unknown. This brief report aimed to understand how
      Twitter users respond to suicide-related content as compared to non-suicide
      related content. Using a dataset of suicide and non-suicide related posts,
      replies, retweets and likes were analysed and compared. The content of the first
      replies to suicide-related posts were also reviewed. When compared to non-suicide
      related posts, those that were suicide-related received a significantly greater
      number of replies, with fewer retweets and likes. The rate of reply to the
      suicide-related posts was also significantly faster than that of the non-suicide
      related posts, with the average reply occurring within 1 h. Thematic analysis
      revealed that 62% of the first replies to suicidal posts were of a potentially
      helpful nature (e.g. discouraging suicide, caring, or clarifying), while 23% were
      dismissive or encouraging of the suicide. These findings indicate that Twitter
      users respond differently to suicidal content. Further research is needed to
      determine the effects of the replies on suicidal intentions or ideations, and
      whether this platform can be used to intervene, increase help-seeking, or provide
      anti-stigma campaigns.

PMID- 30206526
TI  - Reader's Forum.

PMID- 30206523
TI  - Using text message reminders in health care services: A narrative literature
      review.
AB  - Introduction: Despite the extensive use of mHealth behavior change interventions,
      questions remain about the use of technology-based reminders in delivering health
      care services. Text messaging, or short message service (SMS), is one reminder
      method that has been extensively researched. Most SMS-reminder research is
      distributed across a range of health care outcomes. The aim of this article is to
      systematically review the aggregate impact of these reminders on overall health
      care outcomes. Methods: A systematic literature review was conducted and yielded
      2316 articles. Studies were included if they used SMS reminders to support
      patient health care outcomes. Study methodology was aligned with the PRISMA
      guidelines for systematic reviews. Results: Following screening, 162 articles met
      inclusion criteria. Of these studies, 93 investigated medical compliance
      reminders and 56 investigated appointment reminders. The review found that nearly
      all the SMS-reminder studies helped improve patient medical compliance and
      appointment reminders. Additionally, researchers reported numerous benefits from
      using SMS reminders, including ease of use, relative inexpensiveness, and rapid
      and automated message delivery. Minimal risks were reported and most participants
      found the reminders to be acceptable. Discussion: Text messages appear to be an
      effective reminder mechanism to promote improved patient appointment and medical
      compliance. Reminders should continue to be evaluated and improved to determine
      the most effective timing and frequency of messages for improving outcomes.

PMID- 30206525
TI  - ICBT in routine care: A descriptive analysis of successful clinics in five
      countries.
AB  - Clinical trials have demonstrated the efficacy of internet delivered cognitive
      behaviour therapy (ICBT) for anxiety and depression. However, relatively little
      is known about the context, operations, and outcomes of ICBT when administered as
      part of routine care. This paper describes the setting, relationship to existing
      health services, procedures for referral, assessment, treatment, patients and
      outcomes of ICBT clinics in Sweden, Denmark, Norway, Canada and Australia. All
      five clinics provide services free or at low cost to patients. All have systems
      of governance to monitor quality of care, patient safety, therapist performance
      and data security. All five clinics include initial assessments by clinicians and
      between 10 and 20 min of therapist support during each week. Published reports of
      outcomes all demonstrate large clinical improvement, low rates of deterioration,
      and high levels of patient satisfaction. Services that require a face to face
      assessment treat smaller numbers of patients and have fewer patients from remote
      locations. The paper shows that therapist-guided ICBT can be a valuable part of
      mental health services for anxiety and depression. Important components of
      successful ICBT services are rigorous governance to maintain a high standard of
      clinical care, and the measurement and reporting of outcomes.

PMID- 30206528
TI  - Accuracy of three-dimensional cephalograms generated using a biplanar imaging
      system.
AB  - Objective: Biplanar imaging systems allow for simultaneous acquisition of lateral
      and frontal cephalograms. The purpose of this study was to compare measurements
      recorded on three-dimensional (3D) cephalograms constructed from two-dimensional
      conventional radiographs and biplanar radiographs generated using a new biplanar
      imaging system with those recorded on cone-beam computed tomography (CBCT)
      generated cephalograms in order to evaluate the accuracy of the 3D cephalograms
      generated using the biplanar imaging system. Methods: Three sets of lateral and
      frontal radiographs of 15 human dry skulls with prominent facial asymmetry were
      obtained using conventional radiography, the biplanar imaging system, and CBCT.
      To minimize errors in the construction of 3D cephalograms, fiducial markers were
      attached to anatomical landmarks prior to the acquisition of radiographs. Using
      the 3D CephTM program, 3D cephalograms were constructed from the images obtained
      using the biplanar imaging system (3D cephbiplanar), conventional radiography (3D
      cephconv), and CBCT (3D cephcbct). A total of 34 measurements were obtained
      compared among the three image sets using paired t-tests and Bland-Altman
      plotting. Results: There were no statistically significant differences between
      the 3D cephbiplanar and 3D cephcbct measurements. In addition, with the exception
      of one measurement, there were no significant differences between the 3D cephcbct
      and 3D cephconv measurements. However, the values obtained from 3D cephconv
      showed larger deviations than those obtained from 3D cephbiplanar. Conclusions:
      The results of this study suggest that the new biplanar imaging system enables
      the construction of accurate 3D cephalograms and could be a useful alternative to
      conventional radiography.

PMID- 30206527
TI  - Histomorphometric evaluation of the bone surrounding orthodontic miniscrews
      according to their adjacent root proximity.
AB  - Objective: This study was conducted to perform histomorphometric evaluations of
      the bone surrounding orthodontic miniscrews according to their proximity to the
      adjacent tooth roots in the posterior mandible of beagle dogs. Methods: Four male
      beagle dogs were used for this study. Six orthodontic miniscrews were placed in
      the interradicular spaces in the posterior mandible of each dog (n = 24). The
      implanted miniscrews were classified into no loading, immediate loading, and
      delayed loading groups according to the loading time. At 6 weeks after screw
      placement, the animals were sacrificed, and tissue blocks including the
      miniscrews were harvested for histological examinations. After analysis of the
      histological sections, the miniscrews were categorized into three additional
      groups according to the root proximity: high root proximity, low root proximity,
      and safe distance groups. Differences in the bone-implant contact (BIC, %) among
      the root proximity groups and loading time groups were determined using
      statistical analyses. Results: No BIC was observed within the bundle bone invaded
      by the miniscrew threads. Narrowing of the periodontal ligament space was
      observed in cases where the miniscrew threads touched the bundle bone. BIC (%)
      was significantly lower in the high root proximity group than in the low root
      proximity and safe distance groups. However, BIC (%) showed no significant
      differences among the loading time groups. Conclusions: Regardless of the loading
      time, the stability of an orthodontic miniscrew is decreased if it is in contact
      with the bundle bone as well as the adjacent tooth root.

PMID- 30206529
TI  - Displacement and stress distribution of the maxillofacial complex during
      maxillary protraction using palatal plates: A three-dimensional finite element
      analysis.
AB  - Objective: The purpose of this study was to analyze initial displacement and
      stress distribution of the maxillofacial complex during dentoskeletal maxillary
      protraction with various appliance designs placed on the palatal region by using
      three-dimensional finite element analysis. Methods: Six models of maxillary
      protraction were developed: conventional facemask (Type A), facemask with
      dentoskeletal hybrid anchorage (Type B), facemask with a palatal plate (Type C),
      intraoral traction using a Class III palatal plate (Type D), facemask with a
      palatal plate combined with rapid maxillary expansion (RME; Type E), and Class
      III palatal plate intraoral traction with RME (Type F). In Types A, B, C, and D,
      maxillary protraction alone was performed, whereas in Types E and F, transverse
      expansion was performed simultaneously with maxillary protraction. Results: Type
      C displayed the greatest amount of anterior dentoskeletal displacement in the
      sagittal plane. Types A and B resulted in similar amounts of anterior
      displacement of all the maxillofacial landmarks. Type D showed little movement,
      but Type E with expansion and the palatal plate displayed a larger range of
      movement of the maxillofacial landmarks in all directions. Conclusions: The
      palatal plate served as an effective skeletal anchor for use with the facemask in
      maxillary protraction. In contrast, the intraoral use of Class III palatal plates
      showed minimal skeletal and dental effects in maxillary protraction. In addition,
      palatal expansion with the protraction force showed minimal effect on the forward
      movement of the maxillary complex.

PMID- 30206530
TI  - Effects of thermoforming on the physical and mechanical properties of
      thermoplastic materials for transparent orthodontic aligners.
AB  - Objective: The aim of this systematic multiscale analysis was to evaluate the
      effects of thermoforming on the physical and mechanical properties of
      thermoplastic materials used to fabricate transparent orthodontic aligners
      (TOAs). Methods: Specimens were fabricated using four types of thermoplastic
      materials with different thicknesses under a thermal vacuum. Transparency, water
      absorption and solubility, surface hardness, and the results of three-point
      bending and tensile tests were evaluated before and after thermoforming. Data
      were analyzed using one-way analysis of variance and Student's t-test. Results:
      After thermoforming, the transparency of Duran and Essix A+ decreased, while the
      water absorption ability of all materials; the water solubility of Duran, Essix
      A+, and Essix ACE; and the surface hardness of Duran and Essix A+ increased. The
      flexure modulus for the 0.5-mm-thick Duran, Essix A+, and eCligner specimens
      increased, whereas that for the 0.75-/1.0-mm-thick Duran and eClginer specimens
      decreased. In addition, the elastic modulus increased for the 0.5-mm-thick Essix
      A+ specimens and decreased for the 0.75-mm-thick Duran and Essix ACE and the 1.0
      mm-thick Essix ACE specimens. Conclusions: Our findings suggest that the physical
      and mechanical properties of thermoplastic materials used for the fabrication of
      TOAs should be evaluated after thermoforming in order to characterize their
      properties for clinical application.

PMID- 30206532
TI  - Evaluation of buccolingual molar inclinations among different vertical facial
      types.
AB  - Objective: The aim of this study was to compare the buccolingual inclination of
      maxillary and mandibular molars in adults with different vertical facial types.
      Methods: Cone-beam computed tomography images of 135 adult patients (age, 20-45
      years) with skeletal Class I maxillomandibular relationships were assigned to
      normodivergent (n = 46), hypodivergent (n = 49), and hyperdivergent groups (n =
      40) according to linear and angular sella-nasion/gonion-menton measurements. The
      normodivergent group consisted of 24 females and 22 males, hypodivergent group of
      26 females and 23 males, and hyperdivergent group of 24 females and 16 males.
      Buccolingual inclination of the maxillary and mandibular first and second molars
      was measured relative to the occlusal plane. One-way analysis of variance was
      used for intergroup comparison. Gender differences were evaluated using
      independent t-tests. Results: Buccolingual molar inclinations did not differ
      significantly between females and males (p > 0.05). There were no statistically
      significant differences among the buccolingual inclinations of the first and
      second maxillary and mandibular molars of the groups (p > 0.05). Conclusions:
      Buccolingual inclinations of maxillary and mandibular molars are similar in
      normodivergent, hyperdivergent, and hypodivergent adults with Class I sagittal
      relationships.

PMID- 30206531
TI  - Pain perception among patients treated with passive self-ligating fixed
      appliances and Invisalign(r) aligners during the first week of orthodontic
      treatment.
AB  - Objective: This study was performed to compare the perception of pain between
      patients treated with passive self-ligating fixed appliances and those treated
      with Invisalign aligners. Methods: This prospective study conducted in Saudi
      Arabia used an estimated sample of 64 patients from a private dental clinic.
      After obtaining written informed consent, the patients were divided into two
      groups; one group (n = 32) was treated using passive self-ligating fixed
      appliances and the other group (n = 32) using Invisalign(r) aligners. Immediately
      after fitting the appliances, the patients' perception of pain was evaluated
      through a close-ended and coded self-administrated questionnaire by using a
      visual analog scale (VAS). Their responses were recorded at 4 hours, 24 hours,
      day 3, and day 7. Mann-Whitney U-test, Kruskal-Wallis test, and Pearson's chi
      square test were performed for statistical analysis. Results: A lower percentage
      of patients treated with Invisalign aligners reported pain than did patients
      treated with passive self-ligating fixed appliances, and these differences were
      statistically significant (p = 0.001). Similarly, the mean VAS score for the
      Invisalign group was significantly lower than that for the passive self-ligating
      fixed appliance group at different intervals during the first week of treatment.
      The intensity of pain with both appliances peaked at 24 hours (mean VAS score,
      3.87) and was lowest (mean VAS score, 1.62) on day 7. Conclusions: During the
      first week of orthodontic treatment, patients treated with Invisalign aligners
      reported lower pain than did those treated with passive self-ligating fixed
      appliances.

PMID- 30206534
TI  - Correction to: Hard- and soft-tissue profiles of the midface region in patients
      with skeletal Class III malocclusion using cone-beam computed tomography
      multiplanar-reconstructed image analysis.
AB  - [This corrects the article on p. 143 in vol. 48, PMID: 29732300.].

PMID- 30206533
TI  - Effects of continuous force application for extrusive tipping movement on
      periapical root resorption in the rat mandibular first molar.
AB  - Objective: The purpose of this study was to clarify the effects of continuous
      force application for extrusive tipping movement and occlusal interference on
      periapical root resorption in the rat mandibular first molar. Methods: We
      constructed an appliance comprising a titanium screw implant with a cobalt
      chromium post as the anchorage unit and a nickel-titanium closed coil spring (50
      cN) as the active unit. Force was applied on the mandibular left first molar of
      rats for 8 (n = 10) and 15 days (n = 10; experimental groups), with the tooth in
      occlusion. Five rats were included as a non-treated control group to examine the
      body effect of the appliance. Active root resorption lacunae, identified using
      tartrate-resistant acid phosphatase, were evaluated in terms of the length,
      depth, and area. Results: The rat mandibular first molars were mesially tipped
      and extruded in the occlusal direction. This mesio-occlusal tipping movement and
      occlusion resulted in the formation of a compression zone and active root
      resorption lacunae in the distoapical third of the distal roots. However, there
      was no significant difference in the amount of root resorption between the two
      experimental groups. The control group did not exhibit any active root resorption
      lacunae. Conclusions: Periapical root resorption was induced by continuous
      extrusive tipping force and occlusal interference in rat mandibular molars. These
      data suggest that we orthodontists had better take care not to induce occlusal
      interference during our orthodontic treatment.

PMID- 30206537
TI  - Treatment of non-odontogenic orofacial pain using botulinum toxin-A: a
      retrospective case series study.
AB  - Background: The purpose of this study was to evaluate the clinical outcomes of
      treatment of non-odontogenic atypical orofacial pain using botulinum toxin-A.
      Methods: This study involved seven patients (seven females, mean age 65.1 years)
      who had non-odontogenic orofacial pain (neuropathic pain and atypical orofacial
      pain) and visited the Seoul National University Bundang Hospital between 2015 and
      2017. All medication therapies were preceded by botulinum toxin-A injections,
      followed by injections in the insignificant effects of medication therapies. Five
      of the seven patients received intraoral injections in the gingival vestibule or
      mucosa, while the remaining two received extraoral injections in the masseter and
      temporal muscle areas. Results: In five of the seven patients, pain after
      botulinum toxin-A injection was significantly reduced. Most of the patients who
      underwent surgery for dental implantation or facial nerve reconstruction
      recovered after injections. However, the pain did not disappear in two patients
      who reported experiencing persistent pain without any cause. Conclusions: The use
      of botulinum toxin-A for the treatment of non-odontogenic neuropathic orofacial
      pain is clinically useful. It is more effective to administer botulinum toxin-A
      in combination with other medications and physical therapy to improve pain.

PMID- 30206536
TI  - Proportions of the aesthetic African-Caribbean face: idealized ratios, comparison
      with the golden proportion and perceptions of attractiveness.
AB  - Background: In the absence of clear guidelines for facial aesthetic surgery, most
      surgeons rely on expert intuitive judgement when planning aesthetic and
      reconstructive surgery. One of the most famous theories regarding "ideal" facial
      proportions is that of the golden proportion. However, there are conflicting
      opinions as to whether it can be used to assess facial attractiveness. The aim of
      this investigation was to assess facial ratios of professional black models and
      to compare the ratios with the golden proportion. Methods: Forty photographs of
      male and female professional black models were collected. Observers were asked to
      assign a score from 1 to 10 (1 = not very attractive, 10 = very attractive). A
      total of 287 responses were analysed for grading behaviour according to various
      demographic factors by two groups of observers. The best graded photographs were
      compared with the least well-graded photographs to identify any differences in
      their facial ratios. The models' facial ratios were calculated and compared with
      the golden proportion. Results: Differences in grading behaviour were observed
      amongst the two assessment groups. Only one out of the 12 facial ratios was not
      significantly different from the golden proportion. Conclusions: Only one facial
      ratio was observed to be similar to the golden proportion in professional model
      facial photographs. No correlation was found between facial ratios in
      professional black models with the golden proportion. It is proposed that an
      individualistic treatment for each ratio is a rather better method to guide
      future practice.

PMID- 30206535
TI  - Calcium pyrophosphate dihydrate deposition disease in the temporomandibular
      joint: diagnosis and treatment.
AB  - Background: Calcium pyrophosphate dihydrate deposition disease (CPDD) is a rare
      disease in the temporomandibular joint (TMJ) space. It forms a calcified crystal
      mass and induces a limitation of joint movement. Case presentation: The calcified
      mass in our case was occupied in the left TMJ area and extended to the
      infratemporal and middle cranial fossa. For a complete excision of this mass, we
      performed a vertical ramus osteotomy and resected the mass around the mandibular
      condyle. The calcified mass in the infratemporal fossa was carefully excised, and
      the segmented mandible was anatomically repositioned. Scanning electronic
      microscopy (SEM)/energy-dispersive X-ray spectroscopy (EDS) microanalysis was
      performed to evaluate the calcified mass. The result of SEM/EDS showed that the
      crystal mass was completely composed of calcium pyrophosphate dihydrate. This
      result strongly suggested that the calcified mass was CPDD in the TMJ area.
      Conclusions: CPDD in the TMJ is a rare disease and is difficult to differentially
      diagnose from other neoplasms. A histological examination and quantitative
      microanalysis are required to confirm the diagnosis. In our patient, CPDD in the
      TMJ was successfully removed via the extracorporeal approach. SEM/EDS
      microanalysis was used for the differential diagnosis.

PMID- 30206538
TI  - Per-oral cross-facial sural nerve graft for facial reanimation.
AB  - Background: Cross-facial nerve graft is considered the treatment of choice for
      facial reanimation in patients with unilateral facial palsy caused by central
      facial nerve damage. In most cases, a traditional parotidectomy skin incision is
      used to locate the buccal and zygomatic branches of the facial nerve. Methods: In
      this study, cross-facial nerve graft with the sural nerve was planned for three
      patients with facial palsy through an intraoral approach. Results: An incision
      was made on the buccal cheek mucosa, and the dissection was performed to locate
      the buccal branch of the facial nerve. The parotid papillae and parotid duct were
      used as anatomic landmarks to locate the buccal branch. Conclusions: The
      intraoral approach is more advantageous than the conventional extraoral approach
      because of clear anatomic marker (parotid papilla), invisible postoperative scar,
      reduced tissue damage from dissection, and reduced operating time.

PMID- 30206539
TI  - Management of the paralyzed face using temporalis tendon transfer via intraoral
      and transcutaneous approach: Temporalis tendon transfer.
AB  - Temporalis tendon transfer is a technique for dynamic facial reanimation. Since
      its inception, nearly 80 years ago, it has undergone a wealth of innovation to
      produce the modern operation. Temporalis tendon transfer is a relatively
      minimally invasive technique for the dynamic reanimation of the paralyzed face.
      This technique can produce significant and appropriate movement of the lateral
      oral commissure, more closely mimicking the normal side. The aim of this article
      is to review the technique of temporalis tendon transfer involving transferring
      of the coronoid process of the mandible with the insertion of the temporalis
      tendon via intra-oral and transcutaneous approach.

PMID- 30206541
TI  - The Effect of Medial Tibial Slope on Anterior Tibial Translation and Short-Term
      ACL Reconstruction Outcome.
AB  - Background  Increased tibial slope has been shown to be associated with higher
      anterior cruciate ligament (ACL) reconstruction failure rate. Little is known
      about the correlation of tibial slope and anterior tibial translation in ACL
      deficient and reconstructed knees as well as the correlation of tibial slope and
      ACL reconstruction outcome. Purpose/Hypothesis  The purpose of this study was to
      investigate the correlation of tibial slope with anterior tibial translation and
      ACL reconstruction outcome. It is hypothesized that increased medial tibial slope
      is associated with increased anterior tibial translation in the ACL deficient
      knee. Medial tibial slope is neither expected to affect anterior tibial
      translation in the ACL reconstructed knee nor short-term ACL reconstruction
      outcome. Materials and Methods  A cohort of 104 patients with unilateral isolated
      ACL deficiency undergoing hamstring ACL reconstruction by a single surgeon
      between 2002 and 2004 was followed up prospectively. Preoperative data were
      collected including patient demographics, time to surgery, subjective and
      objective International Knee Documentation Committee (IKDC) outcome scores, as
      well as manual maximum anterior tibial translation measured with the KT-1000
      measuring instrument. Medial tibial slope was assessed on long lateral X-rays
      using the method described by Dejour and Bonnin (1994). Intraoperative data were
      collected including meniscal integrity; postoperative data were collected at 1
      year follow-up including manual maximum anterior tibial translation (KT-1000
      measured), and subjective and objective IKDC scores. Results  A significant
      positive correlation was seen between medial tibial slope in ACL deficient knees
      and KT-1000-measured anterior tibial translation ( r  = 0.24; p  = 0.003). The
      positive relationship increased when meniscal integrity was factored in ( r  =
      0.33; p  < 0.001). No significant correlation was seen between medial or lateral
      meniscal integrity and KT-1000-measured anterior tibial translation ( r  = -18; p
      = 0.06). No significant correlation was seen between KT-1000-measured anterior
      tibial translation and time to surgery. One year postoperatively, 82 patients
      were assessed, while 26 patients were lost to follow-up; no significant
      correlation was found between increased medial tibial slope and poor ACL
      reconstruction outcome measured by post-ACL reconstruction anterior tibial
      translation (KT-1000) or subjective and objective IKDC scores. Conclusion 
      Increased medial tibial slope is associated with increased (KT-1000 measured)
      anterior tibial translation in ACL deficient knees. No significant correlation is
      found between increased medial tibial slope and poor short-term ACL
      reconstruction outcome.

PMID- 30206540
TI  - Clinical reliability of zirconium abutment in implant restorations in the English
      and Korean literature.
AB  - Background: This study aimed to evaluate the mechanical, biological, and esthetic
      stability of a zirconium abutment according to evidence-based dentistry. Main
      text: An electronic search was performed. Domestic studies were found using the
      keywords "zirconia abutments" and "zirconium abutment" in KMbase, KoreaMed, and
      the National Assembly Library, and international studies were found using the
      same keywords in PubMed. All identified studies were divided by evidence level
      from the viewpoint of the research type utilizing the evidence-based review
      manual. A total of 102 domestic studies (with Korean language) were found, and 9
      of these studies were selected. In these nine studies, 3 had evidence level 3 and
      6 had evidence level 4. A total of 97 international studies (with English
      language) were found, and 19 were selected. Among these 19 studies, 5 had
      evidence level 2 and 7 had evidence level 3, whereas the remainder had evidence
      level 4. According to the studies, zirconium abutments are mechanically,
      biologically, and esthetically stable, but the evidence level of these studies is
      low, and the follow-up duration is no longer than 5 years. Conclusions: All
      examined studies verified the mechanical stability of zirconium abutments for a
      period no longer than 5 years. Therefore, a long-term clinical observation is
      needed. Zirconium abutments are thought to be biologically stable, but they are
      not superior to titanium abutments. As the esthetic stability of such abutments
      had a low evidence level in the studies that examined here, a much higher
      evidence level is needed.

PMID- 30206543
TI  - Complex Vascular Ring Diagnosed on Cardiovascular MR in a 3-Day-Old Infant.
AB  - Prenatal ultrasonography in the early third trimester showed an unusual branching
      pattern of the right aortic arch. Echocardiography performed 4 h after birth
      showed the right aortic arch with mirror-image branching, patent ductus
      arteriosus, and patent foramen ovale. Because the location of the ductus
      arteriosus was unclear on echocardiography, cardiovascular magnetic resonance
      imaging was performed 3 days after birth. Advanced techniques including contrast
      enhanced time-resolved magnetic resonance angiography and 3D time-of-flight
      magnetic resonance angiography allowed accurate diagnosis of a vascular ring
      comprising ascending and descending aorta, right aortic arch with mirror-image
      branching, and diverticulum of Kommerell giving rise to a left ligamentum
      arteriosum. The infant had hiccups, but no other symptoms. The esophagram was
      negative for obstruction. The infant was closely monitored; however, she
      developed esophageal obstruction at 7 months of age because of the vascular ring.
      She underwent lysis of the left ligamentum arteriosum followed by aortopexy for
      relief of esophageal obstruction. This report shows the utility of neonatal
      cardiovascular magnetic resonance imaging to evaluate complex congenital aortic
      arch anomalies.

PMID- 30206542
TI  - Olfactory Nerve Schwannoma: A Case Report and Review of the Literature.
AB  - Schwannomas are benign tumors, which arise from the Schwann cells of the central
      or peripheral nerves. They form 8% of all intracranial tumors and most of the
      cases arise from vestibular division of the 8 th cranial nerve. Rare cases are
      shown to arise from the olfactory or optic nerve, being devoid of myelin sheath.
      Up to date and according to our best of knowledge, 66 cases have been reported
      till now. Here we present a review of the literature and a case report of a 56
      year-old male with an accidently discovered anterior cranial fossa schwannoma,
      following a road traffic accident. Tumor was completely excised, using a right
      frontal approach. Histopathology revealed Antoni-A cellular pattern. Although
      rare, but olfactory nerve schwannomas should be included in the differential
      diagnosis in anterior cranial fossa space occupying lesions, and the approach
      should be designed taking into consideration, this rare entity.

PMID- 30206546
TI  - Dual-Energy CT-Derived Iodine Content and Spectral Attenuation Analysis of
      Metastatic Versus Nonmetastatic Lymph Nodes in Squamous Cell Carcinoma of the
      Oropharynx.
AB  - The presence of a single nodal metastasis has significant prognostic and
      treatment implications for patients with head and neck cancer. This study aims to
      investigate whether dual-energy computed tomography (DECT)-derived iodine content
      and spectral attenuation curve analysis can improve detection of nodal metastasis
      in oropharyngeal carcinoma. Eight patients with newly diagnosed oropharyngeal
      squamous cell carcinoma and pathologically proven nodal metastatic disease (n =
      13 metastatic nodes; n = 16 nonmetastatic nodes) who underwent contrast-enhanced
      DECT of the neck were retrospectively evaluated. DECT-derived iodine content
      (mg/mL) and monoenergetic attenuation values at 40 keV and 100 keV were obtained
      via circular regions of interest within metastatic and nonmetastatic cervical
      lymph nodes. Iodine content was significantly lower in metastatic nodes (0.96 +/-
      0.28 mg/mL) than in nonmetastatic nodes (1.65 +/- 0.38 mg/mL; P = .002). Iodine
      spectral attenuation slope was significantly lower in metastatic nodes (1.33 +/-
      0.49 mg/mL) than in nonmetastatic nodes (1.91 +/- 0.64 mg/mL; P = .015). A nodal
      iodine threshold of <=1.3 mg/mL showed a sensitivity of 84.6% and a specificity
      of 75.0%, with an area under the curve of 0.839, P < .0001. At a threshold value
      of <=1.95 for nodal spectral attenuation slope, an optimized specificity of 92.3%
      and specificity of 50.0% was achieved, with an area under the curve of 0.68 (P =
      .049). DECT-derived quantitative iodine data and spectral attenuation curves may
      improve the diagnostic accuracy of computed tomography for nodal metastasis in
      patients with squamous cell carcinoma of the oropharynx.

PMID- 30206547
TI  - What's Old Is New Again: The Sacroiliac Joint as a Cause of Lateralizing Low Back
      Pain.
AB  - It has not been easy to identify mechanical failure of the sacroiliac joint (SIJ)
      with traditional imaging. The integrated model of function (Lee and Vleeming,
      1998) suggests that under normal circumstances, form and force closure combined
      contribute to sacral nutation and "locking" the SIJ for optimal load transfer.
      This model is supported by clinical evidence and scintigraphic findings that
      contribute to successful therapy in 80% of cases. Single-photon emission computed
      tomography and x-ray computed tomography (SPECT-CT), a hybrid device, was used in
      a study of 1200 patients (64% female and 36% male patients with an average age of
      42 years; range, 15-78 years) with a clinical diagnosis of SIJ incompetence
      (pelvic girdle pain syndrome). Standard clinical testing and an alternate series
      of tests were used as a reference standard for imaging. Symptoms were present for
      a mean of 43 months. Imaging finding were of increased uptake in the upper SIJ
      (S1-S2), with extension into the dorsal interosseous ligament and measurable by
      count profile. Associated findings of tendon enthesopathy reflected altered
      biomechanics around the pelvis. Ipsilateral adductor enthesopathy was found in
      70% and contralateral hamstring enthesopathy in 60% of patients. SPECT-CT
      criteria for the diagnosis of SIJ incompetence were developed and validated.
      SPECT-CT is a valid and reproducible technique for the diagnosis of SIJ
      incompetence with high concordance and specificity compared to the reference
      standards. Findings are supportive of the integrated model of SIJ function
      proposed by Lee and Vleeming.

PMID- 30206545
TI  - Characterization of an Orthotopic Rat Model of Glioblastoma Using Multiparametric
      Magnetic Resonance Imaging and Bioluminescence Imaging.
AB  - Glioblastoma multiforme (GBM) is the most common primary brain tumor, with most
      patients dying within 15-18 months of diagnosis despite aggressive therapy.
      Preclinical GBM models are valuable for exploring GBM progression and for
      evaluating new therapeutics or imaging approaches. The rat C6 glioma model shares
      similarities with human GBM, and application of noninvasive imaging enables
      better study of disease progression. Here, multiparametric magnetic resonance
      imaging (mpMRI) and bioluminescence imaging (BLI) were applied to characterize
      longitudinal development of orthotopic luciferase-expressing C6 tumors. Across
      all rats (n = 11), a large variability was seen for BLI signal, a relative
      measure of C6 cell viability, but in most individuals, BLI signal peaked at day
      11 and decreased thereafter. T2 and contrast-enhanced T1 tumor volumes
      significantly increased over time (P < .05), and volume measures did not
      correlate with BLI signal. After day 11, tumor regions of noncontrast enhancement
      appeared in postcontrast T1-weighted magnetic resonance imaging, and had
      significantly higher apparent diffusion coefficient values compared with contrast
      enhanced regions (P < .05). This suggests formation of ill-perfused, necrotic
      regions beyond day 11, which were apparent at end-point-matched tissue sections.
      Our study represents the first combined use of BLI and mpMRI to characterize the
      progression of disease in the orthotopic C6 rat model, and it highlights the
      variability in tumor growth, the complementary information from BLI and mpMRI,
      and the value of multimodality imaging to better characterize tumor development.
      Future application of these imaging tools will be useful for evaluation of
      treatment response, and should be pertinent for other preclinical models.

PMID- 30206550
TI  - Retinology: Green-light ahead for innovation.

PMID- 30206551
TI  - Medical malpractice regulation. Civil, administrative, and criminal liability.
AB  - The evolution of the modern Romanian society reveals an increasing trend as to
      the liability for medical malpractice, which in correlation with recent
      amendments of relevant legislation should make healthcare professionals increase
      their awareness in this matter. In the analysis below, malpractice was defined
      from a theoretical and practical perspective, and approached from its potential
      consequences. As liability for malpractice could be variable subject to the
      nature and importance of the damages incurred, the analysis herein describes the
      civil, administrative, and criminal liability in general, as well as the main
      causes for the occurrence of malpractice (e.g. professional errors, lack of
      information and consent of the patients, reuse of single-use medical devices,
      etc.). Furthermore, a few recommendations have been further provided in order to
      eliminate or diminish malpractice from the healthcare professionals and medical
      institutions day-to-day activity.

PMID- 30206549
TI  - Multi-modal Analgesic Strategies for Trauma (MAST): protocol for a pragmatic
      randomized trial.
AB  - Background: Pain management after injury is critically important for functional
      recovery. Although opioids have been a mainstay for treatment of pain, they are
      associated with adverse events and may contribute to long-term use or abuse.
      Opioid-minimizing multimodal pain regimens have the potential to reduce exposure
      to opioids without compromising pain control. This article details an ongoing
      clinical trial comparing two pill-based, opioid-minimizing, multimodal pain
      strategies. Methods: This is a single-center, parallel-group, randomized,
      controlled comparative effectiveness trial comparing two multimodal pain regimens
      in adult trauma patients. All patients 16 years and older admitted to the Red
      Duke Trauma Institute are eligible unless they are pregnant, a prisoner, under
      observation status, or a non-acute trauma patient. At admission to the trauma
      service, patients are enrolled and randomized to one of two multimodal pain
      regimens. The primary outcome is opioid use, measured by morphine milligram
      equivalents per patient per day. The secondary outcomes include pain scores,
      ventilator days, hospital and intensive care unit lengths of stay, occurrence of
      opioid-related complications, hospital and pharmacy costs, and incidence of
      hospital discharge with opioid prescription. Outcomes will be compared using
      Bayesian methods. Discussion: This trial will determine the effectiveness of two
      multimodal pain treatment strategies on reducing in-hospital opioid exposure in
      adult trauma patients. Furthermore, it will compare the two strategies on pain
      control and patient safety. Knowledge gained in this study can improve quality of
      care at this hospital and other trauma centers regardless of which medication
      regimen proves superior.

PMID- 30206552
TI  - Goldenhar Syndrome - ophthalmologist's perspective.
AB  - Goldenhar syndrome (oculo-auriculo-vertebral dysplasia, OAVS) is a rare,
      congenital disease arising from the abnormal development of the first and second
      branchial arches. The incidence is between 1:3500 and 1:5600, with a male: female
      ratio of 3:2. The etiopathogenesis is multifactorial and dependent on genetic and
      environmental factors but there are still many unknown aspects. The classic
      features of Goldenhar syndrome include ocular anomalies - epibulbar dermoids,
      microphthalmia and coloboma, ENT features such as preauricular tragi, hearing
      loss, low implantation of the auricular pavilion, micrognathia, and vertebral
      anomalies such as scoliosis or hemivertebrae. The abnormalities are unilateral in
      85% of the cases. Ocular features, especially bilateral dermoids are seen in 60%
      of the cases. The treatment varies with age and systemic associations, from
      mainly cosmetic, in uncomplicated cases, to complex reconstructive surgeries in
      severe cases. While the oculoplastic surgeon manages the oculo-palpebral defects,
      severe forms require a multidisciplinary approach. Treatment should be
      individualized, adapted to age, as well as to the extent and severity of the
      disease. The paper is based on the editorial team cases and experience.

PMID- 30206544
TI  - Longitudinal Measurements of Intra- and Extracellular pH Gradient in a Rat Model
      of Glioma.
AB  - This study presents the first longitudinal measurement of the
      intracellular/extracellular pH gradient in a rat glioma model using noninvasive
      magnetic resonance imaging. The acid-base balance in the brain is tightly
      controlled by endogenous buffers. Tumors often express a positive pH gradient
      (pHi - pHe) compared with normal tissue that expresses a negative gradient.
      Alkaline pHi in tumor cells increases activity of several enzymes that drive
      cellular proliferation. In contrast, acidic pHe is established because of
      increased lactic acid production and subsequent active transport of protons out
      of the cell. pHi was mapped using chemical exchange saturation transfer, whereas
      regional pHe was determined using hyperpolarized 13C bicarbonate magnetic
      resonance spectroscopic imaging. pHi and pHe were measured at days 8, 12, and 15
      postimplantation of C6 glioma cells into rat brains. Measurements were made in
      tumors and compared to brain tissue without tumor. Overall, average pH gradient
      in the tumor changed from -0.02 +/- 0.12 to 0.10 +/- 0.21 and then 0.19 +/- 0.16.
      Conversely, the pH gradient of contralateral brain tissue changed from -0.45 +/-
      0.16 to -0.25 +/- 0.21 and then -0.34 +/- 0.25 (average pH +/- 1 SD) Spatial
      heterogeneity of tumor pH gradient was apparent at later time points and may be
      useful to predict local areas of treatment resistance. Overall, the
      intracellular/extracellular pH gradients in this rat glioma model were
      noninvasively measured to a precision of ~0.1 pH units at 3 time points. Because
      most therapeutic agents are weak acids or bases, a priori knowledge of the pH
      gradient may help guide choice of therapeutic agent for precision medicine.

PMID- 30206555
TI  - A marketing perspective on consumer perceived competition in private
      ophthalmology services.
AB  - Competition in health care services has been considered as a core component in
      the consumer value mechanism. In Romania, the emergence of private ophthalmology
      services has as outcome a positive-sum competition which focuses on prevention,
      diagnosis and treatment of eye related diseases and disorders and improved value.
      The purpose of this paper was to provide an insight into the knowledge used by
      consumers when they make a decision regarding a private ophthalmology service
      with a specific interest on competition. A research model was elaborated and
      included quality, price, and satisfaction as components influenced by competition
      from the consumers' perspectives. The model was validated using Structural
      Equation Modeling in SmartPLS. The sample was made up of 120 respondents and the
      sampling technique was quota. The structural model revealed that competition has
      a positive impact on satisfaction and explained 74% of its variance and also that
      competition has a positive impact on price and explained 7% of the variance.
      Moreover, using IPMA matrix analysis, the most powerful item of competition
      construct with an influence on satisfaction was the one related to the reputation
      of the private ophthalmology organization. Nonetheless, the key to gain
      competitive advantage stands in providing meaningful value to consumers using
      differentiation features such as high prices, reputation, and awareness on the
      services offered, greater availability, and the most important feature,
      innovation.

PMID- 30206553
TI  - The use of biologic therapies in uveitis.
AB  - PURPOSE: Non-infectious uveitis has been long controlled with the use of
      corticosteroids with many side effects and poor control in some cases. The
      purpose of this paper was to assess the different biologic agents (in this case
      infliximab and adalimumab) and to compare their efficacy in the treatment of
      uveitis. RESULTS: Adalimumab has been proven very successful in replacing or
      aiding corticosteroid therapy in different autoimmune mediated uveitis (Juvenile
      Idiopathic Arthritis, Rheumatoid arthritis, sarcoidosis) whereas infliximab has
      been used intravenously and recently intravitreally with very promising results
      in controlling Behcet's related uveitis. CONCLUSION: Biologic Response Modifiers
      represent the future of therapy in immune-mediated uveitis. Abbreviations AU =
      Anterior Uveitis, BCVA = Best Corrected Visual Acuity, BRM = Biologic Response
      Modifiers, CME = Cystoid Macular Oedema, CPR = C Protein Reactive, ESR =
      Erythrocyte Sediment Rate, HSV = Herpes Simplex Virus, ICAM = Intercellular
      Adhesion Molecules, IMT = Immunomodulatory Therapy, JIA = Juvenile Idiopathic
      Arthritis, MMP = Matrix Metalloproteinases, MTX = Methotrexate, RA = Rheumatoid
      Arthritis, TB = Tuberculosis, VCAM = Vascular Adhesion Molecules.

PMID- 30206548
TI  - Manganese-Enhanced Magnetic Resonance Imaging for Detection and Characterization
      of Colorectal Cancers.
AB  - Here, we investigated the diagnostic performance of manganese (Mn)-enhanced
      magnetic resonance imaging (MEMRI) in colorectal cancer (CRC). The ability of CRC
      cell lines SW620 and SW480 to uptake Mn was evaluated and compared with a normal
      colon cell using MEMRI. Subcutaneous xenografts in nude mice underwent MRI
      examination at tumor sizes of 5, 10, and 15 mm. Contrast enhancement was compared
      between gadolinium (Gd)- and Mn-enhanced MRI. SW620 and SW480 cell lines took up
      more Mn2+ than normal cells, resulting in 4.5 and 2 times greater T1 value
      shortening than normal cell using in vitro MEMRI (P < .001). Most xenografts
      (17/23) enhanced markedly on MEMRI. A heterogeneous enhancement pattern
      invariably noted whether Mn or Gd agents were administered, but tumors imaged
      using MEMRI showed a greater degree of enhancement with a larger extent of
      enhanced area than those imaged using Gd-enhanced MRI. The numbers of markedly Mn
      enhanced cases were more in the 5-mm-size tumor group than in 10- or 15-mm-size
      tumor groups. Overall, MEMRI could enhance CRCs and it showed potential in
      detecting early small lesions and markedly enhancing tumors that had minimal Gd
      enhancement.

PMID- 30206554
TI  - Advances in the treatment of uveitis in patients with spondyloarthritis - is it
      the time for biologic therapy?
AB  - Spondyloarthritis (SpA) is a heterogeneous group of diseases that includes
      ankylosing spondylitis (AS), psoriatic arthritis (PsA), reactive arthritis (ReA),
      inflammatory bowel disease-associated spondyloarthritis (IBD-SpA), and
      undifferentiated spondyloarthritis (unSpA). This group of diseases shares several
      clinical, imaging, and genetic features; the integration of these diseases in the
      group of SpA is needed for an early diagnosis and a prompt treatment. Uveitis is
      the most common extra-articular manifestation of SpA. HLA-B27-associated acute
      anterior uveitis (AAU) is the most frequent form of uveitis encountered in the
      SpA group. The general prevalence of HLA-B27-associated AAU in the group of SpA
      is about 30% and the general prevalence of SpA in patients with HLA-B27
      associated AAU is over 50%. There are several differences in the clinical picture
      and evolution of HLA-B27-associated AAU in patients with SpA and knowing this is
      very important for the best therapeutic decision. Tumor necrosis factor alpha
      (TNFalpha) is a very important mediator not only in the pathogenic mechanisms of
      SpA, but also in the immune reactions that characterize HLA-B27-associated AAU in
      SpA. There is much evidence of the role of TNFalpha in SpA and HLA-B27-associated
      AAU, multiple studies showing efficacy of anti-TNFalpha drugs not only on
      rheumatic manifestations but also on ocular involvement. Conventional therapy of
      HLA-B27-associated AAU with local or systemic glucocorticoids and
      immunosuppressive drugs (sulfasalazine, methotrexate, azathioprine, etc.) in
      order to diminish the ocular inflammation is associated with many side effects,
      some of them being very severe and even life threatening. Therefore, new
      treatments, especially biologic therapy with anti-TNFalpha drugs, open a new
      opportunity for the treatment of these patients. It is very important to
      emphasize that antibody anti-TNFalpha agents (infliximab, adalimumab, golimumab)
      may be more efficient than soluble receptors of TNFalpha (etanercept) in
      decreasing the risk of HLA-B27-associated AAU in patients with SpA. The aim of
      this review made by a group of ophthalmologists and rheumatologists with recent
      and fruitful experience regarding the anti-TNF treatment of uveitis in patients
      with SpA is to make the community of ophthalmologists aware of this biologic
      therapy and that it is the right time to use it. Abbreviations: AU = anterior
      uveitis; AAU = acute anterior uveitis; AS = ankylosing spondylitis; ASAS =
      Assessment of SpondyloArthritis Society; DBP = vitamin D binding protein; ESSG =
      European Spondyloarthropathy Study Group; HLA-B27 = human leukocyte antigen B27;
      IBD = inflammatory bowel disease; PsA = psoriatic arthritis; ReA = reactive
      arthritis; SpA = spondyloarthritis; TLRs = Toll-like receptors; TNFalpha = tumor
      necrosis factor alpha; unSpA = undifferentiated spondyloarthritis.

PMID- 30206556
TI  - Phacoemulsification in adult patients with post-uveitis complicated cataract.
AB  - Objective: To evaluate the difficulties, complications and outcome of cataract
      surgery in patients with complicated cataract after anterior uveitis. Methods: A
      retrospective study on 37 patients who suffered phacoemulsification surgery for
      post-uveitis complicated cataract in the period 2009-2014 was performed. 43 eyes
      underwent surgery. Results: Posterior synechiae were present in 25 eyes.
      Posterior synechiolysis ensured large pupil in 15 eyes, and, in 14 eyes, the use
      of iris hooks or pupil expansion ring was necessary for surgery. Posterior
      capsule rupture was reported in 1 eye. Opacified and thick posterior capsule was
      noticed in 6 eyes. After surgery, transient rising of intraocular pressure was
      noticed in 4 eyes and prolonged postoperative inflammation was present in 3 eyes.
      Posterior capsule opacification was the most frequent issue (9 eyes) and cystoid
      macular oedema was reported in 2 eyes. Conclusions: Post-uveitis complicated
      cataract surgery presents specific difficulties and postoperative complications
      are present in these patients, like prolonged postoperative inflammation and
      cystoid macular oedema.

PMID- 30206557
TI  - Peripapillary retinal nerve fiber layer and macular ganglion cell complex
      thickness in patients with chronic phase of nonarteritic anterior ischemic optic
      neuropathy.
AB  - Objective: We aimed to investigate the peripapillary retinal nerve fiber layer
      (pRNFL) and macular ganglion cell complex (mGCC) thickness in patients with
      chronic phase of nonarteritic anterior ischemic optic neuropathy (crNAION)
      analyzed by spectral domain optical coherence tomography (SD-OCT). Methods:
      Patients with crNAION, and healthy control subjects were enrolled in the study.
      All participants underwent SD-OCT for measurement of pRNFL, mGCC, and central
      macular thickness (CMT). The measurements of the eyes of the patients with
      crNAION were compared with those of the control subjects and unaffected fellow
      eyes. Results: A total of 25 patients with crNAION were eligible for the study.
      The control group consisted of 50 healthy subjects. The pRNFL and mGCC thickness
      in eyes with crNAION were found to be significantly thinner in all quadrants when
      compared to those of healthy control subjects and unaffected fellow eyes. The CMT
      of the eyes with crNAION was similar to that of the healthy control subjects.
      Conclusions: We demonstrated that mGCC and pRNFL thickness measurement by SD-OCT
      are capable of detecting axonal damage in eyes with crNAION. Furthermore, this
      study used SD-OCT and found that mGCC and pRNFL had the ability to detect GC loss
      in the eyes of the patients with crNAION.

PMID- 30206558
TI  - Choroidal thickness increase after micropulse transscleral cyclophotocoagulation.
AB  - Glaucoma, the affliction that results in optic nerve damage and vision loss, is
      the main cause of irreversible blindness. The goal of this study was to describe
      our experience and OCT findings regarding glaucoma patients who underwent
      MicroPulse Transscleral Cyclophotocoagulation. A variety of glaucoma patients
      treated with MP-TSCPC were included in our study. LASER settings were 2000mW of
      810nm infrared diode micropulse LASER, 31.3% duty cycle and the duration of
      treatment was between 80-130 s per hemisphere to each eye, at 3 mm of
      corneoscleral limbus, spearing the nasal and temporal clock hours and also the
      region with previous filtration surgeries (trabeculectomy). We conducted a
      prospective study in which twenty-two patients underwent MP-TSCPC under local
      anaesthesia and they were examined one week, one month, three months, and six
      months postoperatively. Mean IOP dropped from 35.23 mmHg preoperatively to
      17.73mmHg (49.67%) at 1 week follow-up, to 21.81 mmHg (38.09%) at 1 month follow
      up, to 22.34 mmHg at 3 months follow-up and to 23.56 mmHg at 6 months follow-up.
      Four patients (15.8%) underwent a second treatment (at 1 month after the initial
      treatment) due to insufficient IOP decrease, two of them with success in lowering
      the IOP postoperatively. By measuring the foveolar choroidal thickness via
      macular OCT scan, we noticed that all responsive patients had a thicker choroid
      one week after the laser treatment, with a steady increase of a mean 7.3% that
      was sustained at one and three months follow-up, while in non-responsive
      patients, the choroidal thickness remained the same postoperatively, or had a
      significant decrease. The increase in choroidal thickness in all patients in whom
      we observed IOP reduction was a significant correlation that supported the
      mechanism of increased uveoscleral outflow obtained from LASER treatment.

PMID- 30206559
TI  - The importance of corneal biomechanics in assessing first degree family members
      of keratoconus patients.
AB  - Aim: to determine the values of biomechanical parameters (corneal hysteresis -
      CH, corneal resistance factor - CRF and keratoconus match index - KMI) in
      patients with keratoconus and their first degree family members. The purpose of
      the present study was to investigate the importance of assessing corneal
      biomechanics in subjects at risk of developing the primary ectasia. Materials and
      methods: 48 participants divided into three groups were analyzed in an
      observational study after a complete ophthalmological exam with the primary focus
      on Ocular Response Analyzer. Results: The mean values of CH, CRF, and KMI in the
      group of relatives were lower compared with the controls but higher when compared
      with keratoconus patients. We noted significant differences of CH and CRF between
      all three groups, while in the case of KMI, only the keratoconus group presented
      statistically significant differences compared with the relatives, respectively
      with the healthy subjects. Conclusions: the decreased values of CH and CRF may
      raise the question whether corneal biomechanics could be an adjuvant tool in the
      screening of a first-degree family member of a keratoconus patient in the attempt
      of the early detection of a possible forme fruste keratoconus.

PMID- 30206561
TI  - Injecting botulinum toxin into the treatment of blepharospasm.
AB  - The present paper is an introduction to this category of therapy, the injection
      of botulinum toxin into blepharospasm and, at the same time, an attempt to
      familiarize our readers with this concept. Our activity in this field started in
      2014; the favorable results we have obtained since then have made us write this
      article. Abbreviations: BEB = Abnormal Benign Essential Blepharospasm, TXB =
      Botulinum Toxin.

PMID- 30206563
TI  - Stromal corneal dystrophy (possible Schnyder's dystrophy) with peripheral corneal
      degeneration - diagnostic and therapeutic challenges.
AB  - Purpose: to highlight the diagnostic and therapeutic challenges in a case with
      central and peripheral corneal lesions. Methods: We present the preoperative
      investigations: anterior segment optical coherence tomography and ultrasound
      biomicroscopy; The excised cornea has been examined histopathologically. Results:
      Preoperative assessment showed that peripheral lesion was not ectatic;
      Histopathological examination points to a possible corneal degeneration, with
      posttraumatic or infectious etiology for the peripheral lesion and gives some
      reasons to sustain the diagnosis of Schnyder's dystrophy for the central lesion.
      Conclusions: The association of different corneal lesions may need many
      investigations to establish the diagnosis and choose the most appropriate
      therapeutic solution.

PMID- 30206564
TI  - Differential Benefit of Two Different Tooth-Borne Rapid Maxillary Expansion
      Appliances in Female Subjects.
AB  - Objective: The aim of the present study was to evaluate the effects of tooth
      borne acrylic-bonded rapid maxillary expansion (RME) appliances with or without
      the anterior teeth anchorage on the skeletal and dentoalveolar structures, as
      well as soft tissues. Methods: This study included 44 patients who were treated
      with two different tooth-borne bonded acrylic RME appliances. Lateral
      cephalometric radiographs were taken before the treatment (T0) and in the post
      retention (T1) phase of the RME treatment. The posterior-bonded RME appliance
      group and full-bonded RME appliance group were created as the two different
      groups of treatment. The following statistical analyses were performed: intra-
      and inter-group comparisons were made using the paired t-test, Wilcoxon test,
      independent t-test, and Mann-Whitney U-test for normal and non-normal
      distribution data. Results: Significant increases were observed in R1-A, R1-ANS,
      R1-U1, R1-AR, R1-St, R1-Li, and R1-Pn in both groups. R1-PNS, R1-Ls, R1-Sn, and
      R1-B' were found to be significantly larger at T1 than at T0 in the posterior
      bonded RME appliance group. R2-A, R2-ANS, R2-L1, R2-A', and R2-Pn were
      significantly larger at T1 than at T0 in the full-bonded RME appliance group. The
      R2-A' was significantly different between the groups. Conclusion: The soft tissue
      A point appears to be the most important differing matter between the two
      different RME appliances, and a full acrylic-bonded RME appliance may be
      beneficial for subjects with a maxillary retrognathic profile.

PMID- 30206565
TI  - Analysis of Six Orthodontic Journals in Science Citation Index and Science
      Citation Index Expanded: A Bibliometric Analysis.
AB  - Objective: To analyze the article type, origin, main affiliation, number of
      publications, authors, and affiliations of six orthodontic journals during two
      intervals of 5 years each (2006-2010 and 2011-2015). Methods: In total, 4879
      articles examined in this study were screened online at the individual journal's
      website. The types of articles and their authorship characteristics in the six
      orthodontic journals [three journals indexed by Science Citation Index (SCI) and
      the others indexed by Science Citation Index Expanded (SCIE)] were recorded.
      Parameters were tested using the Pearson chi-square for independence at a 0.05
      level of significance. Results: Among all the article types, research articles
      were the most published in the orthodontic journals indexed by SCI and SCIE in
      the first (2006-2010; 88.1% and 77.6%, respectively) and second periods (2011
      2015; 84.4% and 74.6%, respectively). In the first and second intervals, the
      European Union was the most common origin among articles accepted by the journals
      listed in SCI (30.1% and 29.2% respectively), whereas Asia/Oceania was the common
      origin among articles accepted by the journals listed in SCIE (44.1% and 43.4%,
      respectively). Conclusion: The articles published in the orthodontics journals
      listed under SCI and SCIE for 2006-2010 and 2011-2015 were significantly
      different in terms of numbers and characteristics.

PMID- 30206560
TI  - A referable clinical pattern of spondyloarthritis-associated uveitis.
AB  - Objective. The aim of the study was to identify a clinical pattern of
      spondyloarthritis (SpA)-associated uveitis in order to facilitate proper
      rheumatologic referral by ophthalmologists. Methods. Demographic data were
      recorded and acute phase reactants were measured using standard methods between
      May and August 2017, for all adult patients (age > 18 years) presenting with
      acute uveitis (standardization of uveitis nomenclature). Afterwards, they were
      referred to a rheumatology clinic to be screened for the 2009 Assessment of
      SpondyloArthritis International Society (ASAS) classification criteria of SpA.
      SpA and non-SpA patients were then compared using appropriate statistical tests
      (significant if p < 0.05). All the patients offered a written informed consent
      and the study was approved by the local ethics committee. Results. The sample
      included 67 subjects, of whom 32 (47.8%) were classified with SpA, of whom 21
      were known with this diagnosis (median disease duration of 13.6 years), while 11
      (34.4% of the SpA subgroup) fulfilled the ASAS classification criteria for SpA
      without a prior diagnosis. Compared to non-SpA patients, SpA patients were more
      frequently male urban dwellers, they were significantly younger, they had a
      higher prevalence of HLA-B27 and recurrent uveitis, and they had higher median of
      C-reactive protein and lower median of white blood counts. Conclusions. Uveitis
      is an important revelatory manifestation of SpA. Young men presenting in an
      ophthalmology department with acute anterior uveitis and inflammatory back pain
      should be referred to a rheumatology unit. Abbreviations: AAU = Acute Anterior
      Uveitis, AS = Ankylosing Spondylitis, ASAS = Assessment Of Spondyloarthritis
      International Society, CRP = C-Reactive Protein, ESR = Erythrocyte Sedimentation
      Rate, HLA = Human Leukocyte Antigen, IBP = Inflammatory Back Pain, IBD =
      Inflammatory Bowel Disease, IL = Interleukin, MRI = Magnetic Resonance Imaging,
      Nsaids = Non-Steroidal Anti-Inflammatory Drugs, SD = Standard Deviation, Spa =
      Spondyloarthritis, Tnfalpha = Tumour Necrosis Factor Alpha, WBC = White Blood
      Count.

PMID- 30206566
TI  - Assessment of the Quality of Life in Moroccan Patients Undergoing Orthognathic
      Surgery.
AB  - Objective: Dentofacial deformities can affect patient "quality of life" (QoL),
      and orthognathic surgery can improve this QoL. The aim of the present study is to
      assess changes in QoL in Moroccan adult patients with dentofacial deformities
      undergoing orthodontic surgical treatment. Methods: 32 patients (21 females and
      11 males; mean age 27+/-5.96 years) completed a specific questionnaire of QoL
      once the surgical phase is completed. The questionnaire includes 22 questions
      marked on a 4-point scale depending on how much the question covered by the
      statement disturbs the respondent. The 22 questions contribute to four aspects:
      social aspects of dentofacial deformities, facial aesthetic, oral function, and
      awareness of dentofacial aesthetics. Results: A significant difference in QoL was
      observed before surgery between men and women. On the other hand, 73.6% stated of
      patients said that they were uncomfortable by their dentofacial appearance before
      surgery, and almost half of the patients have made functional limitations before
      surgery. After surgery, 85.42% of patients reported a positive change in their
      QoL. Class III patients reported greater pre-surgical aesthetic and functional
      restrictions than Class II skeletal patients. In post-surgery, patients in both
      skeletal classes showed significant improvement in their QoL, so improving the
      aesthetics, oral functions and self-confidence are the main motivators to seek
      orthognathic treatment for our patients. Conclusion: Improving the aesthetics,
      oral functions and self-confidence are the main motivators to seek orthognathic
      treatment for Moroccan patients.

PMID- 30206567
TI  - Three-Dimensional Imaging in Orthodontics.
AB  - Orthodontic records are one of the main milestones in orthodontic therapy.
      Records are essential not only for diagnosis and treatment planning but also for
      follow-up of the case, communicating with colleagues, and evaluating the
      treatment outcomes. Recently, two-dimensional (2D) imaging technology, such as
      cephalometric and panoramic radiographs and photographs, and plaster models were
      routinely used. However, after the introduction of three-dimensional (3D)
      technologies (laser scanner, stereophotogrammetry, and computed tomography) into
      dentistry, 3D imaging systems are more and more commonly preferred than 2D,
      especially in cases with craniofacial deformities. In fact, 3D imaging provided
      more detailed and realistic diagnostic information about the craniofacial hard as
      well as soft tissue and allowed to perform easier, faster, and more reliable 3D
      analyses. The purpose of this review is to provide an overview of the 3D imaging
      techniques, including their advantages and disadvantages, and to outline the
      indications for 3D imaging.

PMID- 30206562
TI  - Bilateral papillary oedema - case report.
AB  - OBJECTIVE: We report one case of malignant high blood pressure with no systemic
      signs but with ocular complaints. METHODS: The paper presents the case of a 31
      year-old male who complained of sudden loss of visual acuity in both eyes. The
      ophthalmological examination revealed bilateral papillary oedema. General and
      cardiological examinations revealed he was suffering from malignant high blood
      pressure. RESULTS: The pathogenic treatment resulted in resolution of signs and
      symptoms with favourable ophthalmological evolution and almost entirely
      functional recovery. Clinical, paraclinical and imagistic data suggested the
      diagnosis of pheochromocytoma. CONCLUSION: This case highlighted ocular
      complications of high blood pressure. The paper summarizes the differential
      diagnosis and management of high blood pressure and reviews the most common
      causes of secondary hypertension in young patients.

PMID- 30206568
TI  - Patient with Severe Skeletal Class II Malocclusion: Double Jaw Surgery with
      Multipiece Le Fort I.
AB  - A 22-year-old woman with severe skeletal Class II malocclusion was referred to
      our clinic. A clinical examination revealed a convex soft tissue profile and
      increased teeth and gingiva exposure both while smiling and in the natural rest
      position. She had Class II molar and canine relationship with increased overjet,
      moderate crowding in both upper and lower jaws, and proclined upper and lower
      incisors. Skeletally, she showed transverse maxillary deficiency, maxillary
      vertical excess, and mandibular retrognathia. We planned orthodontic-orthognathic
      surgery with multipiece Le Fort I osteotomy and bilateral sagittal split
      osteotomy (BSSO) to achieve ideal occlusion, stability, and facial esthetics.
      During orthodontic decompensation to relieve the crowding and to gain an ideal
      incisor inclination, four bicuspid extractions were performed. Because we used
      continuous mechanics, at the end of the decompensation period, we cut the
      maxillary arch wire distal to the lateral incisors into three pieces and waited
      for 3 months for vertical and transversal dental relapse. During the double jaw
      surgical procedure, the maxilla expanded and impacted with multisegmented Le Fort
      I osteotomy and the mandible advanced with BSSO. After the orthodontic and
      orthognathic surgical treatment, the skeletal and dental imbalance was corrected,
      and functional occlusion and dental and skeletal Class I relationship were
      achieved. The treatment results were stable at the 1-year follow-up.

PMID- 30206569
TI  - Editorial: From open-access to 'predatory' publishing.

PMID- 30206570
TI  - Durability of Resin Bonding to Zirconia Using Products Containing 10
      Methacryloyloxydecyl Dihydrogen Phosphate.
AB  - PURPOSE: To examine the durability of composite bonding to zirconia after
      artificial aging using different products containing 10-methacryloyloxydecyl
      dihydrogen phosphate (MDP). MATERIALS AND METHODS: Conditioning methods were:
      none (control [Ctr]; Clearfil SA Luting [CSL]; Panavia SA Luting Plus [PSLP]),
      MDP-containing zirconia primers (Z-Prime Plus [ZP]; Clearfil Ceramic Primer
      [CCP]), and MDP-containing universal adhesives (Single Bond Universal [SBU];
      Clearfil Universal Bond [CUB]). For the Ctr, ZP, CCP, SBU, and CUB groups, the Y
      TZP plates were bonded with MDP-free composite cement. For the remaining two
      groups, each Y-TZP plate was bonded with one of MDP-containing self-adhesive
      composite cements (CSL; PSLP). The specimens in each group (n = 30) were divided
      into two subgroups, with one subgroup of samples subjected to 24-h water storage
      and the other to aging through 30,000 thermocycles plus 180-day water storage.
      Shear bond strength (SBS) was measured. For each conditioning method, inductively
      coupled plasma-mass spectrometry (ICP-MS) was used to quantify the release of
      phosphorus, and microleakage was evaluated through a methylene-blue dyeing
      technique. RESULTS: The Ctr group exhibited the lowest SBS regardless of aging.
      Thermocycling and water storage significantly decreased the SBS in all groups,
      with the exception of the groups with the MDP-containing zirconia primers. Groups
      with MDP-containing universal adhesives and self-adhesive composite cements
      presented brand-dependent higher SBS, even after aging. ICP-MS detected
      phosphorus release from all of the MDP-containing products. Microleakage was
      identified at the interfaces of all bonded specimens, with the highest rate
      detected in the Ctr group. CONCLUSION: MDP-containing primers, universal
      adhesives, and composite cements create bonds to zirconia with acceptable
      strength after long-term aging.

PMID- 30206571
TI  - Efficacy of Plasma Treatment for Decontaminating Zirconia.
AB  - PURPOSE: To evaluate the influence of contamination and plasma treatment on the
      bond strength of resin to zirconia ceramic. MATERIALS AND METHODS: After
      immersion in saliva or the use of a silicone disclosing agent, polished and
      airborne-particle abraded zirconia specimens were cleaned either ultrasonically
      in 99% isopropanol or with nonthermal plasma. Uncontaminated zirconia specimens
      were used as control. For chemical analysis, specimens of all groups were
      examined with x-ray photoelectron spectroscopy (XPS). Plexiglas tubes filled with
      composite resin were bonded to ceramic specimens with a phosphate-monomer
      containing luting resin. The influence of contamination and cleaning methods on
      ceramic bond durability was examined by tensile testing after 3 and 150 days of
      water storage, with an additional 37,500 thermocycles during the 150-day storage.
      RESULTS: XPS showed an increase in the amount of oxygen and a decrease in the
      amount of carbon on the zirconia surface after plasma treatment. After
      contamination with silicone, XPS revealed a high amount of Si residue on the
      surface that none of the investigated cleaning processes could completely remove.
      The tensile bond strength to uncontaminated zirconia ceramic was durable, but was
      significantly reduced by contamination. CONCLUSION: Plasma treatment was
      effective in removing salivary contamination but not silicone disclosing agent
      residue from the bonding surface of zirconia.

PMID- 30206572
TI  - A Randomized, Controlled, Split-mouth Trial Evaluating the Clinical Performance
      of High-viscosity Glass-ionomer Restorations in Noncarious Cervical Lesions: Two
      year Results.
AB  - PURPOSE: To compare the two-year clinical performance of high-viscosity glass
      ionomer (Hv-GIC) restorations in noncarious cervical lesions with nanohybrid
      composite restorations applied with a three-step etch-and-rinse adhesive
      (E&Ra/nanoC). MATERIALS AND METHODS: One hundred thirty-four noncarious cervical
      lesions were included and assigned to two groups according to the split-mouth
      design. The cervical lesions in the experimental group were restored with an Hv
      GIC (Equia, GC), while a nanohybrid composite (G-aenial, GC) with a three-step
      etch-and-rinse adhesive (Optibond FL, Kerr) was applied as the control. All
      tested restorative materials were used according to the manufacturers'
      instructions. Clinical evaluation was performed after one week, six months, one
      year, and two years using World Dental Federation criteria. Data were analyzed
      using Friedman's ANOVA and Mann-Whitney U-tests (alpha = 0.05). RESULTS: After
      two years, Hv-GIC restorations had a retention rate of 91% in comparison to 100%
      for E&Ra/nanoC restorations. Significant differences existed between the two
      restorative materials solely with respect to the retention parameter after two
      years (p = 0.008). CONCLUSIONS: The two-year clinical performance of Hv-GIC was
      clinically acceptable. However, the retention of E&Ra/nanoC restorations was
      significantly better than that of Hv-GIC restorations after two years.

PMID- 30206573
TI  - Does Luting Strategy Affect the Fatigue Behavior of Bonded Y-TZP Ceramic?
AB  - PURPOSE: To evaluate the effect of different luting strategies on the fatigue
      failure load (FFL) and stress distribution of Y-TZP disks luted to epoxy resin
      substrate. MATERIALS AND METHODS: Y-TZP disks (diameter = 10 mm; thickness = 0.7
      mm) were assigned to five groups according to the luting strategy (n = 15): CC:
      no zirconia surface treatment, composite cement; G_CC: application of a thin
      glaze layer on zirconia followed by hydrofluoric acid etching and silanization,
      composite cement; Al_CC: air abrasion of the zirconia surface with 125-um Al2O3
      particles, composite cement; Si_CC: tribochemical silica coating (30-um SiO2
      particles), composite cement; ZP: air abrasion of the zirconia surface with 125
      um Al2O3 particles, zinc-phosphate cement. The disks were luted to the epoxy
      resin substrate. The FFL was evaluated by the step-test method. The load was
      applied in stages of 10,000 cycles, starting with 600 N, followed by increments
      of 200 N. Samples were loaded until fracture or to a maximum of 100,000 cycles.
      FFL data were submitted to Kaplan-Meier (alpha = 0.05) and Weibull analyses.
      Conditions simulating a strong and a weak bond between Y-TZP and epoxy resin were
      evaluated in the finite element analysis (FEA). RESULTS: Luting strategy
      influenced the FFL (p < 0.001) and the stress distribution of Y-TZP disks. Al_CC
      (2227 +/- 149 N) and Si_CC (2133 +/- 235 N) showed the highest FFL values,
      followed by CC (1800 +/- 293 N) and G_CC (1280 +/- 147 N), while ZP showed the
      lowest FFL value (680 +/- 101 N). The highest Weibull modulus occurred in Al_CC
      (18.2). A strong bond reduced the tensile stress concentration in the Y-TZP
      luting surface, while a weak bond between Y-TZP and the epoxy resin favored the
      concentration of tensile stresses. CONCLUSION: Air abrasion with aluminum oxide
      and silica-coated alumina particles improves the FFL of bonded Y-TZP. Zinc
      phosphate cement should be used very carefully in the cementation of zirconia
      restorations, since it results in lower values of FFL than composite cements.

PMID- 30206574
TI  - Influence of Ambient Air and Different Surface Treatments on the Bonding
      Performance of a CAD/CAM Composite Block.
AB  - PURPOSE: To evaluate the bond strengths of time elapsed after sandblasting with
      alumina particles on a CAD/CAM composite block treated with different surface
      conditioning methods. MATERIALS AND METHODS: A CAD/CAM composite block (CCB) was
      cut into 72 slices of approximately 2 mm thickness. The CCB slices were divided
      into three groups according to sandblasting pressure (0.1 MPa, 0.2 MPa, or
      untreated), and then divided into two subgroups according to the time elapsed
      after sandblasting: same-day or one-week dry storage under controlled laboratory
      conditions before cementation. Surface roughness was observed by confocal laser
      microscopy (CLSM) (n = 20); then the wettability of the CCB surfaces was examined
      using a contact angle (CA) measuring device on a droplet of deionized water (n =
      12). Next, CCB slices were divided into three subgroups according to the surface
      treatment: Clearfil Ceramic Primer (CP), Clearfil Universal Bond (UB), or a
      mixture of Clearfil Porcelain Bond Activator and Clearfil tri-S Bond ND Quick
      (NDP). All CCB slices were then cemented with Panavia V5 and stored at 37 degrees
      C in distilled water for 24 h and cut into sticks (n = 10). The sticks were
      subjected to microtensile bond strength (uTBS) testing, and failure mode analysis
      was performed using scanning electron microscopy. The uTBS results were subjected
      to 3-way and 2-way ANOVA (alpha = 0.05). RESULTS: All groups showed a
      statistically significant increase in wettability accompanied by decreased uTBS
      after one week; however, the UB group exhibited stable performance after one
      week. CONCLUSION: The time elapsed after sandblasting with alumina particles
      affects the bond strength, but it had no significant effect on the UB group.

PMID- 30206575
TI  - Dentin Bond Strength of Experimental Composites Containing Bioactive Glass:
      Changes During Aging for up to 1 Year.
AB  - PURPOSE: To investigate dentin bond strength of experimental composites based on
      a bis-GMA/TEG-DMA composite filled with a varying amount (0 to 40 wt%) of
      bioactive glass 45S5 (BG) at a total filler content of 70 wt%. MATERIALS AND
      METHODS: Specimens for shear bond strength testing (diameter = 3.12 mm, height =
      3 mm) were bonded to human dentin using a two-step self-etch adhesive and
      subjected to aging in water at 37 degrees C for 1 week, 1 month, 3 months, 6
      months, and 1 year. A total of 600 specimens were prepared (6 materials * 5 aging
      times * 20 specimens per experimental group). Bond strength was tested by loading
      specimens in a universal testing machine at a constant crosshead speed of 0.5
      mm/min until fracture. Reliability analysis was performed using Weibull
      statistics. RESULTS: Experimental composites with a low BG content (up to 5 wt%)
      showed dentin bond strength and reliability comparable to those of the commercial
      reference composite. A further increase in the BG amount diminished both bond
      strength and reliability. The bond strength decline was linearly dependent on the
      amount of BG when observed within each aging time. One-year aging in water caused
      no deterioration of bond strength, but diminished bond reliability. The
      reliability after 1-year aging was similar among all composites, including the
      commercial reference composite. CONCLUSION: The variation in BG amount diminished
      the bond strength and reliability in a dose-dependent manner.

PMID- 30206576
TI  - Can the Use of a Warm-Air Stream for Solvent Evaporation Lead to a Dangerous
      Temperature Increase During Dentin Hybridization?
AB  - PURPOSE: To analyze the effect of a warm-air stream for solvent evaporation on
      the temperature rise in the pulp chamber during dentin hybridization. MATERIALS
      AND METHODS: Dentin disks with thicknesses of 0.5, 1.0 and 1.5 mm were obtained
      from extracted human molars. A model tooth was set up with the dentin disks
      between a molar with an exposed pulp chamber and a crown with an occlusal
      preparation. A K-type thermocouple connected to a digital thermometer was placed
      in the molar root until it entered the pulp chamber and made contact with the
      dentin disks. After 10 s of adhesive application, solvent evaporation was
      performed for 10, 20, 30, and 40 s and the increase in temperature was monitored
      for 200 s after the warm-air stream began. RESULTS: The temperature increase was
      significantly influenced by the thickness of the dentin disks (0.5 mm = 1.0 mm >
      1.5 mm). With respect to the duration of the warm-air stream, the temperature
      increase was as follows: 10 s < 20 s < 30 s < 40 s (p < 0.05). The highest
      temperature was found after 40 s with dentin disks that were 0.5 mm (16.6 degrees
      C) and 1.0 mm (15.8 degrees C) thick, whereas the lowest temperature increase
      occurred after 10 s with a dentin disk that was 1.5 mm thick (4.1 degrees C) (p <
      0.05). CONCLUSION: The temperature in the pulp chamber was strongly influenced by
      the dentin thickness and the duration of the warm-air stream. Thinner dentin and
      a longer duration of the warm-air stream both lead to a greater temperature
      increase in the pulp chamber.

PMID- 30206578
TI  - Effect of Composite Polymerization Stress and Placement Technique on Dentin
      Micropermeability of Class I Restorations.
AB  - PURPOSE: To investigate the effect of polymerization stress and insertion
      technique on dentin micropermeability of composites placed under pulpal pressure.
      MATERIALS AND METHODS: One high-viscosity conventional (HC; Filtek Supreme Ultra;
      3M Oral), one low-viscosity conventional (LC; Filtek Supreme Ultra Flowable; 3M
      Oral), one high-viscosity bulk fill (HBF; Filtek Bulk Fill Restorative; 3M Oral),
      and one low-viscosity bulk fill (LBF; Filtek Bulk Fill Flowable; 3M Oral)
      composite were evaluated. Polymerization stress was measured with materials
      bonded to acrylic rods in a universal testing machine (n = 5). Class I
      preparations were made in extracted molars, in which tooth roots were removed and
      the pulpal chambers cleaned. Preparations were coupled to a hydraulic device to
      simulate pulpal pressure during composite placement (n = 5). Conventional
      composites were placed in two horizontal increments, while bulk fill materials
      were placed in one, single increment. Fluid flow rate (ul/min) and dentin
      micropermeability (%) were monitored. The restoration interface was observed
      under confocal laser scanning microscopy. RESULTS: LC and LBF presented
      statistically significant higher polymerization stress than HC and HBF. Fluid
      flow rate and dentin micropermeability did not differ among the groups. However,
      different patterns of fluid infiltration and interface integrity were observed.
      HC and HBF presented well-sealed surrounding margins with small gaps along the
      pulpal wall, while HBF demonstrated more cracks in the adhesive layer. LC and LBF
      restorations had larger gaps along all bonded interfaces. CONCLUSION: No
      difference in polymerization stress was found when conventional and bulk fill
      composites with similar viscosities were compared. Neither polymerization stress
      or placement technique demonstrated a significant effect on dentin
      micropermeability. The incremental placement technique using a conventional, high
      viscosity composite exhibited qualitatively better marginal integrity.

PMID- 30206580
TI  - Functionalization of [60]fullerene through fullerene cation intermediates.
AB  - Fullerene cations, namely [60]fullerene radical cation (C60+) and
      organo[60]fullerenyl cation (RC60+), are less investigated as intermediates in
      synthetic fullerene chemistry because of the intrinsic electronegativity of C60.
      Remarkably, these two intermediates can mediate reactions that afford versatile,
      unique and unexpected fullerene derivatives. This review article mainly describes
      these C60+ and RC60+ intermediates and includes a variety of topics, from the
      generation of C60+ and RC60+ species to their applications in fullerene
      modification reactions, such as Friedel-Crafts hydroarylation, nucleophilic
      addition, dimerization, intramolecular rearrangement reactions, and
      intramolecular cyclization reactions. Additionally, this review deeply discusses
      the mechanism of the formation of unique [60]fullerene derivatives involving
      [60]fullerene radical cation and organo[60]fullerenyl cation intermediates. In
      addition, the electrochemical properties and photovoltaic performance of these
      fullerene derivatives produced through C60+ or RC60+-mediated reactions are
      discussed in this review.

PMID- 30206577
TI  - Treatment of an Adolescent Patient with Dentinogenesis Imperfecta Using Indirect
      Composite Restorations - A Case Report and Literature Review.
AB  - PURPOSE: To demonstrate the field of application and prospects of individually
      modeled indirect composite restorations for the treatment of children and
      adolescents based on a case of dentinogenesis imperfecta. Dental malformations
      can affect single or multiple teeth. In most cases, direct composite fillings can
      be placed. However, in severe cases, these restorations may be more challenging
      and error-prone, especially when occlusal adjustments are necessary. Since
      composite materials do not require a specific lamination strength and are easy to
      repair, they can be applied using the indirect technique, enabling conservation
      of more sound hard tissue than is possible when conventional restorations are
      used. PATIENT AND METHODS: A young patient with dentinogenesis imperfecta type II
      underwent interdisciplinary full-mouth rehabilitation due to massive tooth wear
      and loss of vertical occlusion. First, a check bite was taken, and vertical
      occlusion was increased using overdentures. Six months later, a construction bite
      was taken over the existing overdentures (focusing on the sagittal dimension) to
      move the mandibular position more towards the anterior, correcting the skeletal
      Class II malocclusion. This resulted in a Class I intercuspidation with
      harmonization of the facial proportions. After a further six months, all teeth
      were restored using individually modeled indirect composite restorations, which
      preserved most of the sound hard tissue and restored esthetics and function.
      CONCLUSION: Indirect composite restorations can be a valuable tool for improving
      occlusion, esthetics and function in the treatment of children and adolescents.

PMID- 30206579
TI  - Efficacy of Natural Collagen Crosslinkers on the Compromised Adhesive Bond
      Strength to NaOCl-treated Pulp Chamber Dentin.
AB  - PURPOSE: To evaluate the efficacy of natural collagen crosslinkers on compromised
      adhesive bond strength to NaOCl-treated pulp chamber dentin. MATERIALS AND
      METHODS: Mesial surfaces of the pulp chamber dentin of 120 extracted human molars
      were obtained. The dentin fragments were divided into six groups according to the
      protocols used: no treatment (negative control), sodium hypochlorite (NaOCl) for
      30 min and final irrigation with 17% EDTA for 3 min (positive control). After
      treatment with NaOCl and EDTA, the dentin surfaces of the experimental groups
      were treated for 5 min with one of the following: grape seed extract (GSE),
      tannic acid (TA), green tea (GT), or n-acetyl cysteine (NAC). Half of the samples
      of each group were bonded with an etch-and-rinse (Single Bond; 3M Oral Care) and
      the other half using a self-etch (Scotchbond Universal; 3M Oral Care) adhesive.
      The restoration was completed with composite. The bonded specimens were sectioned
      to produce sticks and subjected to the microtensile bond strength test. Data were
      analyzed by two-way ANOVA and Tukey's HSD test (p < 0.05). RESULTS: Both
      adhesives had similar bond strengths (p > 0.05). The NaOCl-treated group had
      significantly lower bond strength than the negative control (p < 0.05). The
      application of NAC did not recover compromised bonding (p > 0.05). On the other
      hand, GSE, TA and GT had significant reversal effects of the bond strengths to
      NaOCl-treated dentin (p < 0.05). CONCLUSION: Compromised bonding of adhesives to
      NaOCl-treated dentin can be reversed by the application of either GSE, TA or GT.

PMID- 30206583
TI  - Flexible colloidal nanocrystal electronics.
AB  - Nanometer-scale crystals of bulk group IV, III-V, II-VI, IV-VI, I-III-VI2, and
      metal-halide perovskite semiconductors, dispersed in solvents, are known as
      colloidal nanocrystals and form an excellent, solution-processable materials
      class for thin film and flexible electronics. This review surveys the size,
      composition, and surface chemistry-dependent properties of semiconductor NCs and
      thin films derived therefrom and provides physico-chemical insight into the
      recent leaps forward in the performance of NC field-effect transistors. Device
      design and fabrication methods are described that have enabled the demonstration
      and scaling up in complexity and area and scaling down in device size of
      flexible, colloidal nanocrystal integrated circuits. Finally, taking stock of the
      advances made in the science and engineering of NC systems, challenges and
      opportunities are presented to develop next-generation, colloidal NC electronic
      materials and devices, important to their potential in future computational and
      in Internet of Things applications.

PMID- 30206581
TI  - Hot electron transfer promotes ion production in plasmonic metal nanostructure
      assisted laser desorption ionization mass spectrometry.
AB  - Plasmonic metal nanostructures have been used as effective materials for
      enhancing the laser desorption ionization (LDI) efficiency in mass spectrometry
      analysis. But the ionization mechanism and the origin of initial charges have not
      been fully understood yet. Here we provided experimental evidence showing that
      the hot electron transfer in localized surface plasmon resonance (LSPR) plays a
      key role in ionizing molecules during the LDI process.

PMID- 30206582
TI  - Composition modulation in one-dimensional and two-dimensional chalcogenide
      semiconductor nanostructures.
AB  - Low dimensional heterostructures have potential applications in information,
      sensing, and energy-related technologies. In order to obtain high-quality low
      dimensional heterostructures, an essential method is tuning chemical composition
      in a single nanostructure to obtain two or multiple components with well-matched
      electronic band structures. Here, we present a tutorial review of a unique
      chemical vapor growth approach with in situ switchable solid chemical sources
      that can build composition-modulated chalcogenide heterostructures in one
      dimensional nanowires, quasi one-dimensional nanobelts and two-dimensional atomic
      layered nanosheets in a controlled manner. This approach has generated a large
      variety of heterostructures that not only exhibit gradient distribution in
      chemical composition, but also show sharp interfaces. Diverse integrated photonic
      and optoelectronic devices are enabled by the composition-modulated
      heterostructures based on chalcogenides or other material systems.

PMID- 30206584
TI  - Performance of TDDFT with and without spin-flip in trajectory surface hopping
      dynamics: cis-trans azobenzene photoisomerization.
AB  - Time-dependent density functional theory (TDDFT) with and without a spin-flip
      scheme is extensively compared in on-the-fly trajectory surface hopping molecular
      dynamics with a global switching (GS) algorithm. The simulation is performed for
      cis-trans azobenzene photoisomerization following the excitation to the S1(npi*)
      state that is involved in a conical intersection (CI) between ground and first
      excited states. This CI is found correctly to be a single-cone (artificial double
      cone) structure computed by the TDDFT method with (and without) spin-flip.
      Nevertheless, simulated quantum yields and lifetimes are in very good agreement;
      0.43 and 63 fs (0.34 and 62 fs) for cis-to-trans isomerization, and 0.11 and 2200
      fs (0.13 and 1040 fs) for trans-to-cis isomerization, by TDDFT with (and without)
      a spin-flip scheme. Distributions of excited-state decay, hopping spots and
      products, as well as typical trajectories have similar patterns and behaviors
      with and without spin-flip. The global switching trajectory surface hopping
      method is demonstrated to be well suited to TDDFT on-the-fly dynamic simulation
      with and without spin-flip. For comparison, previous simulations with the CASSCF
      method and Tully's fewest-switches trajectory surface hopping method are also
      addressed.

PMID- 30206586
TI  - Noble metal-free V2O5/g-C3N4 composites for selective oxidation of olefins using
      hydrogen peroxide as an oxidant.
AB  - Vanadium pentoxide modified graphitic carbon nitride (V2O5/g-C3N4) composites
      were prepared through a method of wet impregnation and calcination. The obtained
      samples were characterized by Fourier transform infrared spectroscopy, X-ray
      diffraction, thermogravimetric analysis, X-ray photoelectron spectroscopy,
      scanning electron microscopy, transmission electron microscopy, UV-Vis diffuse
      reflectance spectroscopy, photoluminescence, electron spin resonance and N2
      adsorption/desorption isotherms. Oxidation of olefins was employed to evaluate
      the catalytic and photocatalytic activities of the prepared V2O5/g-C3N4
      composites. Different weight ratios (1%, 2%, 3%, 4% and 5%) of V2O5 loaded
      composites were prepared and a 3% loaded composite was found to show optimal
      catalytic performance for the reaction. This noble metal-free catalyst showed
      excellent performance in the oxidation of styrene to benzaldehyde with high
      conversion (98.7%) and selectivity (88.4%) under visible light irradiation. A
      plausible mechanism was proposed for this oxidation reaction with hydrogen
      peroxide as an oxidant. Other styrene substrates were also selectively
      transformed to their corresponding aldehydes with high yields (up to 92%), using
      such a noble metal-free catalytic system.

PMID- 30206587
TI  - From strong to weak NF bonds: on the design of a new class of fluorinating
      agents.
AB  - A set of 50 molecules with NF bonds was investigated to determine the factors
      that influence the strength of a NF bond, with the aim of designing a new class
      of fluorinating agents. The intrinsic bond strength of the NF bonds was used as
      bond strength measure, derived from local stretching NF force constants obtained
      at the CCSD(T)/aug-cc-pVTZ and omegaB97XD/aug-cc-pVTZ levels of theory. The
      investigation showed that the NF bond is a tunable covalent bond, with bond
      strength orders ranging from 2.5 (very strong) to 0.1 (very weak). NF bond
      strengthening is caused by a combination of different factors and can be achieved
      by e.g. ionization. Whereas, the NF bond weakening can be achieved by
      hypervalency on the N atom, using a N->Ch (Ch: O, S, Se) donor-acceptor type bond
      with different electron-withdrawing groups. These new insights into the nature of
      the NF bond were used to propose and design a new class of fluorinating agents.
      Hypervalent amine-chalcogenides turned out as most promising candidates for
      efficient electrophilic fluorinating agents.

PMID- 30206585
TI  - A water-stable homochiral luminescent MOF constructed from an achiral acylamide
      containing dicarboxylate ligand for enantioselective sensing of penicillamine.
AB  - A water-stable homochiral luminescent metal-organic framework (HLMOF),
      {[Cd(l)(4,4'-bipy)].DMA.5H2O}n (1), was obtained by a spontaneous symmetry
      breaking crystallization from achiral precursors without any enantiopure
      auxiliary. The homochirality of 1 was confirmed by single-crystal X-ray
      diffraction and CD spectroscopy. Complex 1 exhibits an interesting
      enantioselective sensing of d/l-penicillamine in water.

PMID- 30206588
TI  - A novel Cs2NbOF5:Mn4+ oxyfluoride red phosphor for light-emitting diode devices.
AB  - The addition of a red-emitting phosphor to YAG:Ce3+-based white light-emitting
      diodes (WLEDs) greatly facilitates their applications in the field of high-color
      rendering-index warm solid-state lighting. It is highly desirable to develop a
      red phosphor with satisfactory spectral features and low synthesis cost. In this
      study, a novel non-rare-earth and nonequivalent doping type of Cs2NbOF5:Mn4+
      oxyfluoride red-emitting phosphor with high luminous efficiency was obtained via
      a facile room-temperature co-precipitation method, and its morphology and
      luminescent properties were investigated in detail. The Cs2NbOF5:Mn4+ phosphor
      with micro-rod-like morphology exhibited broad band absorption at blue light
      region (~474 nm) and narrow bandwidth emissions at red region (~633 nm). The
      color purity of the Cs2NbOF5:Mn4+ phosphor was calculated to be about 99%, and
      the internal quantum yield (QY) under 474 nm excitation was 63.4%. The
      concentration quenching of Mn4+ in Cs2NbOF5 matrix was mainly due to dipole
      dipole interactions, and the activation energy of temperature quenching was
      calculated to be ~0.2610 eV. The demonstration of a blue InGaN LED chip in
      combination with a blend of newly developed Cs2NbOF5:Mn4+ red phosphor and
      YAG:Ce3+ yellow phosphor greatly decreased the correlated color temperature (CCT)
      from 6255 to 3517 K while significantly improving the color rendering index (CRI)
      from 72.5 to 87.5. It deserves to be mentioned that the brand-new matrix to
      phosphor in the present study can be extended to various niobium/tantalum
      oxyfluoride series, which is very helpful for developing and designing new red
      phosphors.

PMID- 30206591
TI  - The mechanism and origin of the regioselectivity of cobalt-catalyzed annulation
      of allenes with benzamide: a computational study.
AB  - Thrimurtulu et al. recently reported unprecedented cobalt-catalyzed annulation of
      allenes with benzamide (N. Thrimurtulu, A. Dey, D. Maiti, C. M. R. Volla, Angew.
      Chem., Int. Ed., 2016, 55, 12361-12365). In this reaction, the substituent on the
      allene controls the regioselectivity for the formation of either
      dihydroisoquinolin-1(2H)-one or isoquinolin-1(2H)-one. In the present study,
      density functional theory calculations were performed to investigate the detailed
      reaction mechanism and the origin of the experimentally observed
      regioselectivity. A systematic search shows that the electronic and steric
      effects of the substituent on the allene determine which of the two allene
      insertions is followed, and thus determine the regioselectivity. The bulky
      diphenylphosphonate and two phenyl substituents of the allenylphosphonate and
      diarylallene favor C1[double bond, length as m-dash]C2 insertion, which
      eventually leads to the formation of isoquinolin-1(2H)-one. In contrast, for the
      arylallene, which has a relatively electron-rich C2[double bond, length as m
      dash]C3 bond, C2[double bond, length as m-dash]C3 insertion is favored and
      eventually leads to the formation of dihydroisoquinolin-1(2H)-one. The
      calculations also explain why annulation rather than hydroarylation of benzamide
      with allenylphosphonate occurs with a cobalt catalyst.

PMID- 30206589
TI  - Effect of structure variations on the quadruplex DNA binding ability of nickel
      Schiff base complexes.
AB  - Two different series of nickel Schiff base complexes were prepared as part of a
      study aimed at discovering new compounds with high affinity and selectivity for
      quadruplex DNA (qDNA). The new complexes were prepared by modification of a
      literature method for synthesising N,N'-bis-(4-((1-(2-ethyl)piperidine)
      oxy)salicylidene)phenylenediaminenickel(ii) (complex (1)). For Series 1
      complexes, the phenylenediamine head group of the literature complex was replaced
      with ethylenediamine, phenanthrenediamine, R,R- and S,S-diaminocyclohexane. These
      complexes, as well as an asymmetric molecule featuring a naphthalene moiety on
      one side and a single ethyl piperidinyl salicylidene group on the other, were
      prepared in order to examine the effect of varying the number and position of
      aromatic groups on DNA binding. Series 2 complexes were isomers of those in
      Series 1, in which pendant ethyl piperidine groups were located at different
      positions. All new complexes were characterised by 1D and 2D NMR spectroscopic
      methods alongside microanalysis and ESI-MS. In addition, the solid state
      structures of eight new complexes were determined using single crystal X-ray
      diffraction methods. N,N'-Bis-(4-((1-(2-ethyl)piperidine)oxy)
      salicylidine)diaminophenanthrenenickel(ii) (9), was shown by ESI-MS, CD
      spectroscopy and UV melting studies to exhibit a greater affinity towards, and
      ability to stabilise, dsDNA than all other complexes in the first series. ESI-MS
      revealed (9) to have a strong tendency to form a 1 : 1 complex with the
      tetramolecular, parallel qDNA molecule Q4, however it exhibited low affinity
      towards the parallel unimolecular qDNA molecule Q1. The enantiomeric complexes
      (5) and (7), featuring R,R- and S,S-diaminocyclohexane moieties, respectively,
      showed similar binding profiles towards all DNA molecules investigated, whereas
      the asymmetric complex (11), exhibited very low DNA affinity in all cases. Series
      2 complexes showed very similar DNA affinity and selectivity to their isomeric
      counterparts in Series 1. For example, (14) and (15), both of which contain a
      phenylenediamine head group, showed higher affinity towards D2, Q1 and Q4, than
      any of the other Series 2 complexes. In addition, complex (21), which contains a
      meso-1,2-diphenylethylenediamine moiety, interacted strongly with Q4, but not D2
      or Q1. This observation was very similar to that made previously for the isomeric
      complex (3).

PMID- 30206592
TI  - Two-electron oxidation of a homoleptic U(iii) guanidinate complex by
      diphenyldiazomethane.
AB  - Reaction of the first homoleptic U(iii) guanidinate complex with
      diphenyldiazomethane results in two-electron oxidation of U(iii) to U(v) and
      isolation of a U(v) hydrazido complex. Corresponding U(v) imido, U(v) oxo, and
      U(iv) azido complexes were also synthesized for structural comparison.

PMID- 30206590
TI  - Weakly interacting solvation spheres surrounding a calixarene-protected
      tetrairidium carbonyl cluster: contrasting effects on reactivity of alkane
      solvent and silica support.
AB  - The tetrairidium carbonyl cluster Ir4L3(CO)9 (L = tert-butyl
      calix[4]arene(OPr)3(OCH2PPh2) (Ph = phenyl; Pr = propyl)) on a partially
      dehydroxylated silica support undergoes hydrogen activation at a rate and with a
      mechanism different from those pertaining to the cluster in alkane solution.
      These results are unobvious in view of the sterically bulky ligands protecting
      the cluster and the nearly identical CO band frequencies in the infrared spectra
      characterizing the supported and dissolved Ir4L3(CO)9, both before reaction and
      during reaction involving decarbonylation in the presence of either helium or H2
      (and H2 reacted with the clusters to form hydrides with the same Ir-H band
      frequencies for clusters in alkane solvent and supported on silica). The initial
      rates of CO loss from the supported clusters in the presence of helium were the
      same as those in the presence of H2. The comparison demonstrates that the rate
      determining step for hydride formation on the silica-supported cluster is CO
      dissociation. In contrast, the comparable dissociation of CO from the cluster in
      n-decane solution requires a higher temperature, 343 K, and is at least an order
      of magnitude slower than when the clusters were supported on silica. CO
      dissociation is not the rate-determining step for hydrogen activation on the
      cluster in n-decane, as the rate is influenced by reactant H2 as well.

PMID- 30206599
TI  - Controlling ion transport through nanopores: modeling transistor behavior.
AB  - We present a modeling study of a nanopore-based transistor computed by a mean
      field continuum theory (Poisson-Nernst-Planck, PNP) and a hybrid method including
      particle simulation (Local Equilibrium Monte Carlo, LEMC) that is able to take
      ionic correlations into account including the finite size of ions. The model is
      composed of three regions along the pore axis with the left and right regions
      determining the ionic species that is the main charge carrier, and the central
      region tuning the concentration of that species and, thus, the current flowing
      through the nanopore. We consider a model of small dimensions with the pore
      radius comparable to the Debye-screening length (Rpore/lambdaD~ 1), which,
      together with large surface charges provides a mechanism for creating depletion
      zones and, thus, controlling ionic current through the device. We report the
      scaling behavior of the device as a function of the Rpore/lambdaD parameter.
      Qualitative agreement between PNP and LEMC results indicates that mean-field
      electrostatic effects predominantly determine device behavior.

PMID- 30206593
TI  - Conformational twisting of a formate-bridged diiridium complex enables catalytic
      formic acid dehydrogenation.
AB  - We previously reported that iridium complex 1a enables the first homogeneous
      catalytic dehydrogenation of neat formic acid and enjoys unusual stability
      through millions of turnovers. Binuclear iridium hydride species 5a, which
      features a provocative C2-symmetric geometry, was isolated from the reaction as a
      catalyst resting state. By synthesizing and carefully examining the catalytic
      initiation of a series of analogues to 1a, we establish here a strong correlation
      between the formation of C2-twisted iridium dimers analogous to 5a and the
      reactivity of formic acid dehydrogenation: an efficient C2 twist appears unique
      to 1a and essential to catalytic reactivity.

PMID- 30206600
TI  - Cyclic OFF/Part/ON switching of single-molecule magnet behaviours via multistep
      single-crystal-to-single-crystal transformation between discrete Fe(ii)-Dy(iii)
      complexes.
AB  - Upon dehydration, a dinuclear Fe(ii)-Dy(iii) cluster {FeDy(H2O)2} undergoes two
      step single-crystal-to-single-crystal (SCSC) transformation, giving another
      dinuclear cluster {FeDy(H2O)} and finally a tetranuclear cluster {Fe2Dy2}.
      Further, both the single crystals of {FeDy(H2O)} and {Fe2Dy2} can return to
      {FeDy(H2O)2} by rehydration. This multistep SCSC transformation leads to notable
      OFF/Part/ON switching of single-molecule magnet behaviour.

PMID- 30206601
TI  - Correction: Boronate based fluorescence (ESIPT) probe for peroxynitrite.
AB  - Correction for 'Boronate based fluorescence (ESIPT) probe for peroxynitrite' by
      Adam C. Sedgwick et al., Chem. Commun., 2016, 52, 12350-12352.

PMID- 30206602
TI  - Complete digestion of edible bird's nest releases free N-acetylneuraminic acid
      and small peptides: an efficient method to improve functional properties.
AB  - Edible bird's nest (EBN), an Asian health food, contains insoluble proteins and
      conjugated N-acetylneuraminic acid (NANA) that are difficult to be absorbed by
      humans. In order to increase the nutritional value of EBN, we developed methods
      to digest EBN targeting the release of proteins and NANA. By using simulated
      gastric fluid under acidic conditions, the complex proteins were fully digested
      into smaller peptides, and in parallel, NANA was fully released from the
      conjugated form. The completely digested EBN showed better nutraceutical
      properties. In a skin whitening test, the EBN digest showed stronger inhibition
      of melanogenesis of cultured B16 cells and enzymatic activity of tyrosinase, as
      compared to that of undigested EBN. In addition, the EBN digest exhibited
      stronger osteogenic activity in cultured osteoblasts. Thus, the complete
      digestion of EBN could be applied to the development of a new generation of EBN
      health food products, including EBN drinks and skincare products.

PMID- 30206603
TI  - A dipotassium 1,2,4-diazaphospholide dianion radical as an organometallic
      building block: the first 1,2-diaza-4-phosphine ruthenocene.
AB  - A persistent dipotassium 3,5-diphenyl-1,2,4-diazaphospholide dianion radical
      {K+2[(3,5-Ph2dp)]2-} (2) was synthesized and investigated by EPR analysis and
      magnetic susceptibility measurement, and it can be used as a transfer agent for
      the preparation of an unusual 1,2-diaza-4-phosphine ruthenocene (4) with
      exclusive sigma(P)-coordination. A plausible mechanism for the formation of 4 was
      proposed as one that involves a reactive radical intermediate {K+[(eta5
      CpMe5Ru)(sigma(P),sigma(C)-(3,5-Ph2dp)]-)} (K+[5A]-) with sigma(P)-coordination
      due to the high spin density (SD) at the phosphorus (sigma2lambda3) atom.

PMID- 30206604
TI  - Solid-state chiral resolution mediated by stoichiometry: crystallizing etiracetam
      with ZnCl2.
AB  - Chiral resolution of racemic etiracetam was achieved via co-crystallization with
      ZnCl2. Depending on the amount of ZnCl2 either a stable racemic compound or a
      stable conglomerate can be obtained. Excess ZnCl2 triggers the quantitative
      conversion of the racemate into the conglomerate solid; this unprecedented
      behaviour was investigated through a racetam/ZnCl2/solvent phase diagram.

PMID- 30206608
TI  - Missing links towards understanding the equilibrium shapes of hexagonal boron
      nitride: algorithm, hydrogen passivation, and temperature effects.
AB  - There is a large discrepancy between the experimental observations and the
      theoretical predictions in the morphology of hexagonal boron nitride (h-BN)
      nanosheets. Theoretically predicted hexagons terminated by armchair edges are not
      observed in experiments; and experimentally observed triangles terminated by
      zigzag edges are found theoretically unstable. There are two key issues in
      theoretical investigations, namely, an efficient and accurate algorithm of the
      absolute formation energy of h-BN edges, and a good understanding of the role of
      hydrogen passivation during h-BN growth. Here, we first proposed an efficient
      algorithm to calculate asymmetric edges with a self-consistent accuracy of about
      0.0014 eV A-1. This method can also serve as a standard approach for other two
      dimensional (2D) compound materials. Then, by using this method, we discovered
      that only when edges are passivated by hydrogen atoms and temperature effects are
      taken into account can experimental morphology be explained. We further employed
      the Wulff construction to obtain the equilibrium shapes of H-passivated h-BN
      nanosheets under their typical growth conditions at T = 1300 K and p = 1 bar, and
      found out that the equilibrium shapes are sensitive to hydrogen passivation and
      the growth conditions. Our results resolved long-standing discrepancies between
      experimental observations and theoretical analysis, explaining the thermodynamic
      driving force of triangular, truncated triangular, and hexagonal shapes, and
      revealing the key role of hydrogen in h-BN growth. These discoveries and the
      advancement in the algorithm may open the gateway towards the realization of 2D
      electronic and spintronic devices based on h-BN.

PMID- 30206607
TI  - Effects of casein phosphopeptides on calcium absorption and metabolism
      bioactivity in vitro and in vivo.
AB  - Casein phosphopeptides (CPPs) are a series of peptides containing serine
      phosphate, which prevents calcium precipitation in the small intestine, so that
      it can be absorbed. Calcium metabolism studies have been typically carried out
      using traditional metabolic balance tests. Non-radioactive stable isotopes have
      rarely been used to examine the in vivo absorption and metabolism of calcium in
      animal models due to their high cost and the difficulty in their accurate
      detection. However, they have recently attracted intense research attention. In
      this study, we developed InertSep ME-1 using a chelating resin to effectively
      separate 42Ca from spectral-interference in the process of ICP-MS detection. The
      method effectively removes interfering ions like potassium and sodium and greatly
      improves the accurate detection of the calcium ion isotope. We also investigated
      the absorption, distribution, and metabolism of different CPPs through both in
      vitro cell experiments and in vivo animal experiments. The results indicate that
      CPPs strongly promote calcium absorption, especially the P5 active monomer
      component. The results of our in vivo studies show that the calcium isotope can
      be absorbed from the small intestine into the blood. Then, one part is
      transported to various organs through tissue fluids while another part is
      excreted into the urine through the kidneys. In general, our results reveal that
      CPPs promote the absorption of calcium significantly and positively affect
      calcium metabolism.

PMID- 30206606
TI  - Two-dimensional materials for miniaturized energy storage devices: from
      individual devices to smart integrated systems.
AB  - Nowadays, the increasing requirements of portable, implantable, and wearable
      electronics have greatly stimulated the development of miniaturized energy
      storage devices (MESDs). Electrochemically active materials and microfabrication
      techniques are two indispensable parts in MESDs. Particularly, the architecture
      design of microelectrode arrays is beneficial to the accessibility of two
      dimensional (2D) active materials. Therefore, this study reviews the recent
      advancements in microbatteries and microsupercapacitors based on
      electrochemically active 2D materials. Emerging microfabrication strategies
      enable the precise control over the thickness, homogeneity, structure, and
      dimension in miniaturized devices, which offer tremendous opportunities for
      achieving both high energy and power densities. Furthermore, smart functions and
      integrated systems are discussed in detail in light of the emergence of
      intelligent and interactive modes. Finally, future developments, opportunities,
      and urgent challenges related to 2D materials, device fabrications, smart
      responsive designs, and microdevice integrations are provided.

PMID- 30206609
TI  - Steered molecular dynamics simulations reveal a self-protecting configuration of
      nanoparticles during membrane penetration.
AB  - Cell entry of polynucleotide-based therapeutic agents can be facilitated by
      nanoparticle (NP) mediated delivery. In this work, using steered molecular
      dynamics simulations, we simulated the membrane penetration process of a NP
      formed by 2 short interfering RNA (siRNA) and 6 polyethylenimine (PEI) molecules.
      To the best of our knowledge, this is the first set of simulations that explore
      the direct penetration of an siRNA/PEI NP through a membrane at an all-atom
      scale. Three types of PEI molecules were used for NP formation: a native PEI, a
      PEI modified with caprylic acids and a PEI modified with linoleic acids. We found
      that hydrogen bond formation between the PEIs and the membrane did not lead to
      instability of the siRNA/PEI NPs during the internalization process. Instead, our
      results suggested adoption of a "self-protecting" configuration by the siRNA/PEI
      NP during membrane penetration, where the siRNA/PEI NP becomes more compact and
      siRNAs become aligned, leading to more stable configurations while detaching from
      the membrane. The siRNA/PEI NP modified with linoleic acid showed the smallest
      structural change due to its strong intra-particle lipid associations and the
      resulting rigidity, while NP modified with caprylic acid showed the largest
      structural changes. Our observations provide unique insight into the structural
      changes of siRNA/PEI NPs when crossing the cell membrane, which can be important
      for the design of new NP carriers for nucleic acid delivery.

PMID- 30206610
TI  - Effect of interfilament hydrodynamic interaction on swimming performance of two
      filament microswimmers.
AB  - The motion of two-filament artificial swimmers is modeled by assuming
      interfilament coupling via hydrodynamic viscous drag. The filaments are assumed
      to be in parallel and attached to a rigid spherical head. The boundary actuation
      is assumed to occur at the head-filament joint through an external oscillatory
      magnetic field and the filament motion is taken to be confined to the flexural
      plane. The hydrodynamic coupling modifies the viscous drag on one filament due to
      motion of the other. Assuming in-phase, small amplitude, low frequency actuation
      the swimmer performance metrics (propulsive thrust, propulsion speed and energy
      efficiency) are calculated using Lauga's formulation for the swimmer kinematics
      coupled with filament dynamics. The results are compared with the performance of
      a single-filament and an uncoupled two-filament swimmer. The hydrodynamic
      coupling is found to enhance the performance measures in a parametric window.
      Also, it is found that there occurs an optimum combination of head size and
      swimmer length that can maximize the microswimmer performance. The findings are
      in agreement with the experimental observations on multi-filament artificial
      microswimming.

PMID- 30206605
TI  - Viscoelastic subdiffusion in a random Gaussian environment.
AB  - Viscoelastic subdiffusion governed by a fractional Langevin equation is studied
      numerically in a random Gaussian environment modeled by stationary Gaussian
      potentials with decaying spatial correlations. This anomalous diffusion is
      archetypal for living cells, where cytoplasm is known to be viscoelastic and a
      spatial disorder also naturally emerges. We obtain some first important insights
      into it within a model one-dimensional study. Two basic types of potential
      correlations are studied: short-range exponentially decaying and algebraically
      slow decaying with an infinite correlation length, both for a moderate (several
      kBT, in the units of thermal energy), and strong (5-10kBT) disorder. For a
      moderate disorder, it is shown that on the ensemble level viscoelastic
      subdiffusion can easily overcome the medium's disorder. Asymptotically, it is not
      distinguishable from the disorder-free subdiffusion. However, a strong scatter in
      single-trajectory averages is nevertheless seen even for a moderate disorder. It
      features a weak ergodicity breaking, which occurs on a very long yet transient
      time scale. Furthermore, for a strong disorder, a very long transient regime of
      logarithmic, Sinai-type diffusion emerges. It can last longer and be faster in
      the absolute terms for weakly decaying correlations as compared with the short
      range correlations. Residence time distributions in a finite spatial domain are
      of a generalized log-normal type and are reminiscent also of a stretched
      exponential distribution. They can be easily confused for power-law distributions
      in view of the observed weak ergodicity breaking. This suggests a revision of
      some experimental data and their interpretation.

PMID- 30206612
TI  - Adsorption and fusion of hybrid lipid/polymer vesicles onto 2D and 3D surfaces.
AB  - We investigated the formation of hybrid lipid/polymer (1,2-dioleoyl-sn-glycero-3
      phosphocholine and poly(ethylene oxide-b-butadiene); DOPC/EO22Bd37) films onto
      planar silica surfaces. Using laser scanning confocal microscopy, atomic force
      microscopy, and quartz crystal microbalance analysis, we monitored the adsorption
      and fusion of hybrid lipid/polymer vesicles onto planar borosilicate glass
      cleaned via chemical etching or RF/air plasma treatment. In addition we used cryo
      electron microscopy to characterize film formation on mesoporous silica
      nanoparticles. As the polymer content in the vesicles increased, the resulting
      hybrid lipid/polymer films on borosilicate glass - cleaned by chemical etching or
      plasma treatment - were more heterogeneous, indicating a large number of adsorbed
      vesicles rather than continuous bilayer films at higher polymer loadings. The
      observed lateral fluidity of both DOPC and hybrid lipid/polymer films also
      decreased substantially with increasing polymer fraction and was found to be
      relatively insensitive to changes in pH. Films prepared from vesicles with higher
      polymer loadings were completely immobile. We also found that polymer vesicles
      did not interact with clean plasma-treated glass surfaces, which may be due to
      elevated OH and Si-OH on plasma-treated surfaces. Conformal hybrid lipid/polymer
      coatings consistent with bilayers could be formed on mesoporous silica
      nanoparticles and imaged via cryo-electron microscopy. These results expand the
      library of biocompatible materials that can be used for coating silica-based
      materials and nanoparticles.

PMID- 30206611
TI  - Enhanced immunofluorescence detection of a protein marker using a PAA modified
      ZnO nanorod array-based microfluidic device.
AB  - Zinc oxide (ZnO) often serves as protein microarray substrates owing to its
      outstanding fluorescence enhancement effect. However, the integration of
      functional substrates with microfluidic technology to detect cancer biomarkers
      still needs to be optimized and promoted, for example, the optimization of
      micro/nanostructure and hydrophilic modification strategies for fluorescence
      immunoassays. Here, ZnO nanorod arrays were constructed on the inner wall of
      glass capillaries through a microfluidic chemical method, and the electrostatic
      layer by layer self-assembly was applied to modify the nanorod array with
      hydrophilic polyelectrolyte-polyacrylic acid (PAA). The effects of the flow rate
      and the reagent concentration on the morphology of the ZnO nanorod array were
      investigated. The ZnO nanorod array-based glass capillary, prepared at 25 MUL min
      1 for 4 min with 50 mM Zn2+ in solution, showed a remarkable enhancement in
      fluorescence performance. In addition, the introduction of PAA suppressed the
      interference of nonspecific protein and improved the antibody loading capacity
      effectively. In the detection of carcinoembryonic antigen, the limit of detection
      reached 100 fg mL-1, which indicated that the ZnO@PAA nanorod array-based
      microfluidic device exhibits remarkable fluorescence detection performance
      towards protein markers and possesses potential to be applied to point-of-care
      diagnostics and high throughput cancer biomarker detection.

PMID- 30206613
TI  - Synthesis of two novel [18F]fluorobenzene-containing radiotracers via spirocyclic
      iodonium ylides and positron emission tomography imaging of translocator protein
      (18 kDa) in ischemic brain.
AB  - Two novel radiotracers, namely, N-(4-[18F]fluorobenzyl)-N-methyl-2-(7-methyl-8
      oxo-2-phenyl-7,8-dihydro-9H-purin-9-yl)acetamide ([18F]5) and 2-(5-(4
      [18F]fluorophenyl)-2-oxobenzo[d]oxazol-3(2H)-yl)-N-methyl-N-phenylacetamide
      ([18F]6), were developed for positron emission tomography (PET) imaging of
      translocator protein (18 kDa) (TSPO) in ischemic brain in this study. The two
      radiotracers with a [18F]fluorobenzene ring were derived from the corresponding
      [18F]fluoroethyl tracers [18F]7 and [18F]8 which underwent
      [18F]defluoroethylation in vivo easily. [18F]5 or [18F]6 was synthesized by the
      radiofluorination of the spirocyclic iodonium ylide precursor 10 or 17 with
      [18F]F- in 23 +/- 10% (n = 7) or 56 +/- 9% (n = 7) radiochemical yields (decay
      corrected, based on [18F]F-). [18F]5 and [18F]6 showed high in vitro binding
      affinities (Ki = 0.70 nM and 5.9 nM) for TSPO and moderate lipophilicities (log D
      = 2.9 and 3.4). Low uptake of radioactivity for both radiotracers was observed in
      mouse bones. Metabolite analysis showed that the in vivo stability of [18F]5 and
      [18F]6 was improved in comparison to the parent radiotracers [18F]7 and [18F]8.
      In particular, no radiolabelled metabolite of [18F]5 was found in the mouse
      brains at 60 min after the radiotracer injection. PET studies with [18F]5 on
      ischemic rat brains revealed a higher binding potential (BPND = 3.42) and maximum
      uptake ratio (4.49) between the ipsilateral and contralateral sides. Thus, [18F]5
      was shown to be a useful PET radiotracer for visualizing TSPO in
      neuroinflammation models.

PMID- 30206615
TI  - Isolation, purification and the anti-hypertensive effect of a novel angiotensin I
      converting enzyme (ACE) inhibitory peptide from Ruditapes philippinarum fermented
      with Bacillus natto.
AB  - Hypertension is known as an important factor in cardiovascular disease. An
      angiotensin-I-converting enzyme (ACE) inhibitor is one of the synthetic drugs
      that is widely used to control hypertension. Here, we have prepared and
      investigated the ACE inhibitory peptide from Ruditapes philippinarum fermented
      with Bacillus natto. The fermented product obtained under optimized fermentation
      conditions exhibited ACE inhibitory activity. The ACE inhibitory peptides were
      purified by ultrafiltration, gel filtration chromatography and RP-HPLC,
      sequentially. A novel peptide with high ACE inhibitory activity (IC50 of 8.16
      MUM) was isolated and the amino acid sequence was identified to be Val-Ile-Ser
      Asp-Glu-Asp-Gly-Val-Thr-His (VISDEDGVTH) by LC-MS/MS. The Lineweaver-Burk plots
      suggested that VISDEDGVTH acts as a competitive inhibitor against ACE. Our in
      vitro study indicated the stability of VISDEDGVTH against gastrointestinal
      proteases. An in vivo study in rats proved the significant anti-hypertension
      effect of the peptide. Furthermore, the cellular mechanism of VISDEDGVTH
      moderating hypertension was investigated. We found that VISDEDGVTH enhanced the
      release of NO, inhibited the secretion of EF-1, and scavenged ROS in human
      vascular endothelial cells. Our study suggests that VISDEDGVTH serves as an anti
      hypertension and anti-inflammatory drug and as a beneficial ingredient in
      functional foods and pharmaceuticals.

PMID- 30206616
TI  - A novel and simple spectrophotometric method for detection of nitrite in water.
AB  - A novel and simple spectrophotometric method is developed for the determination
      of nitrite in water by using the self-coupling diazotization reagent 2-amino-6
      chlorobenzoic acid and UV light illumination. The method only involves one
      reagent and one step, which can be easily applied to the determination of nitrite
      and tolerates many foreign anions' effects under acidic conditions.

PMID- 30206617
TI  - 3D shape change of multi-responsive hydrogels based on a light-programmed
      gradient in volume phase transition.
AB  - We present a new multi-responsive hydrogel based on oligo(ethylene glycol)
      methacrylate (OEGMA) and incorporating the photosensitive monomer 4
      acetoxystyrene (AOST). Light irradiation creates a gradient in the volume phase
      transition temperature (VPTT) across the hydrogel, resulting in stimuli
      responsive 3D deformations, with a largest achievable bending angle of 354
      degrees . The gradient hydrogels exhibited controllable, reversible and
      repeatable 3D deformations driven by changes in temperature or ionic strength.
      Multiple complex shape changes were achieved through patterned illumination.

PMID- 30206618
TI  - A positive impact on the serum lipid profile and cytokines after the consumption
      of a plant sterol-enriched beverage with a milk fat globule membrane: a clinical
      study.
AB  - The hypocholesterolemic effect and the modification of serum biomarkers of a
      dietary plant sterol (PS) intake, cholesterol precursors and cytokines after the
      consumption of milk-based fruit beverages with a milk fat globule membrane were
      evaluated by a randomized, double-blind, crossover, multiple dose bioavailability
      study. Postmenopausal women (n = 38) consumed daily 250 mL of a beverage with or
      without 2 g of PS added during 6 weeks in each of the study periods. With the
      intake of the PS-added beverage, significant decreases (mg dL-1) in serum total
      cholesterol (pre-treatment: 220.0 +/- 27.8 vs. post-treatment: 212.9 +/- 25.8; p
      < 0.05) and LDL-cholesterol (129.4 +/- 28.5 vs. 121.7 +/- 24.4; p < 0.05) were
      detected. The cholesterol precursor lathosterol (11.2%), markers of the dietary
      PS intake (campesterol 43.1% and beta-sitosterol 32.5%), and anti-inflammatory IL
      10 cytokine (22.5%) increased significantly, with a concomitant significant
      reduction in pro-inflammatory IL-1beta (6.7%). No variations in HDL-cholesterol,
      other sterols (desmosterol and stigmasterol) or cytokines (IL-6, IL-8, IL-12p70
      and TNF-alpha) were detected. These results indicated that this kind of PS
      enriched milk-based fruit beverage is suitable during the period of clinical
      intervention, and its consumption may be an adequate way to improve PS
      functionality since a significant reduction in cholesterol levels has been
      observed. Therefore, the intake of this beverage could contribute to reduce the
      risk of cardiovascular disease also obtaining a beneficial effect on the serum
      inflammatory status in postmenopausal women.

PMID- 30206614
TI  - Copper-boryl mediated organic synthesis.
AB  - Organoboron compounds are valuable synthetic intermediates that find application
      in a diverse variety of processes including both C-X and C-C bond-forming
      transformations. This has been achieved by using a variety of boron derivatives.
      Of these, boronate esters are probably the most versatile and, reflecting this,
      methods for the generation of boronate esters are of considerable current
      interest. Given the mild reaction conditions, good functional group tolerance,
      and low cost of the metal catalyst, the use of copper-boryl reagents is
      particularly attractive. In this review, methodologies in copper-boryl chemistry
      are discussed and the many different transformations possible are surveyed.

PMID- 30206619
TI  - Polymer stabilization of cholesteric liquid crystals in the oblique helicoidal
      state.
AB  - Electrical control of the pitch has been reported in a variant of the cholesteric
      liquid crystal phase composed of chiral dopants and liquid crystal dimers with a
      bent conformation, such as CB7CB. For a finite range of applied electric field,
      the dimeric mesogens assume an oblique helicoidal structure, in which the helical
      axis is aligned along the electric field and the local director is tilted towards
      the helical axis (rather than being perpendicular to it). An electric field can
      directly regulate the periodicity (pitch), allowing reconfiguration of the
      optical response from a scattering or transparent state to a reflective state.
      Here, we employ po stabilization to retain the oblique helicoidal state absent an
      applied field. The polymer stabilized oblique helicoidal structures were
      investigated under various conditions and material compositions. With polymer
      stabilization, the magnitude of the selective reflection is found to be dependent
      on the strength of the applied field. Comparison of the electro-optical response
      of samples with and without a polymer network elucidates the relative role of
      boundary conditions, anchoring strength, and elastic energy on the stability of
      the oblique helicoidal state.

PMID- 30206621
TI  - A rapid cell-permeating turn-on probe for sensitive and selective detection of
      sulfite in living cells.
AB  - A rapid cell-permeating probe NJUXJ-1 was introduced for sensitive and selective
      detection of sulfite in living cells. It generated a turn-on response to sulfite
      with high sensitivity (detection limit 13.0 nM) and selectivity (at a
      physiological level) and low toxicity. The fluorescence of the detecting system
      was steady for a wide pH range (5-8) and a long period of time (over 12 h). The
      most attractive point, its rapid cell-permeating ability, made it suitable for
      bioimaging with a 2 min incubation time and shortened the whole detecting period
      (cell-permeation and reaction), and thus could decrease background interference.
      It offered a convenient approach for determining exogenous or endogenous sulfite
      levels in living cells and further applications.

PMID- 30206623
TI  - Cerium(iii)-directed assembly of glutathione-capped gold nanoclusters for sensing
      and imaging of alkaline phosphatase-mediated hydrolysis of adenosine
      triphosphate.
AB  - Aggregation-induced emission enhancement (AIEE) of thiolated gold nanoclusters
      (AuNCs) has emerged as an attractive and alternative strategy to improve their
      brightness. This study demonstrates Ce(iii)-triggered AIEE of glutathione-capped
      AuNCs (GSH-AuNCs) through the coordination between two carboxylic groups of GSH
      and Ce(iii). The cluster size and valence state of GSH-AuNCs are almost identical
      to those of a Ce(iii)-induced assembly of GSH-AuNCs (named Ce(iii)-GSH-AuNCs).
      More importantly, the as-prepared Ce(iii)-GSH-AuNCs exhibit a higher quantum
      yield (up to 13%), longer luminescence lifetime, and shorter maximum luminescence
      peak than GSH-AuNCs. Additionally, Ce(iii)-GSH-AuNCs possess redox-switchable
      luminescence, high salt stability, and long-term storage stability. These
      findings provide clear evidence that the Ce(iii)-triggered aggregation of GSH
      AuNCs is a crucial factor to improve the luminescence property of GSH-AuNCs.
      Intriguingly, the presence of adenosine triphosphate (ATP) switches off the
      luminescence of Ce(iii)-GSH AuNCs through the significant formation of Ce(iii)
      ATP complexes. Furthermore, the ATP-induced luminescence quenching of Ce(iii)-GSH
      AuNCs can be paired with the alkaline phosphatase (ALP)-ATP system to design a
      turn-on luminescent probe for ALP; the limit of detection for ALP is estimated to
      be 0.03 U L-1. Also, the biocompatibility of Ce(iii)-GSH-AuNCs enables the
      proposed system to detect ALP in human serum and HeLa cells.

PMID- 30206622
TI  - Towards understanding of lanthanide-transition metal bonding: investigations of
      the first Ce-Fe bonded complex.
AB  - The syntheses, structural, and magnetic characterization of three new
      organometallic Ce complexes stabilized by PyCp22- (PyCp22- = [2,6
      (CH2C5H3)2C5H3N]2-) are reported. Complex 1 provides the first example of a
      crystallographically characterized unsupported Ce-Fe bond in a molecular
      compound. Results from IR spectroscopy and computational analyses suggest weaker
      Fe -> Ce electron-donation than in a previously reported Dy-Fe bonded species.

PMID- 30206624
TI  - Palladium triggered diene formation from nitro allylic compounds: a versatile
      entry into naphthalene derivatives.
AB  - Nitro allylic derivatives were converted into dienes through the elimination of
      the nitro group under basic treatment, in the presence of a palladium catalyst.
      This reaction probably involves the formation of a palladium pi-allyl complex
      followed by a base-promoted beta-hydride elimination. This reaction, combined
      with the condensation of ketones with nitromethane and the functionalization of
      the resulting nitrocycloalkenes, constitutes a very powerful synthetic tool for
      the formation of dienes. Particular attention has been brought to the application
      of this methodology to the formation of 1-substituted naphthalenes from 1
      tetralone.

PMID- 30206626
TI  - Popcorn-shaped polyethylene synthesised using highly active supported
      permethylindenyl metallocene catalyst systems.
AB  - Unsymmetrical permethylindenyl bent metallocene complexes have been synthesised
      and reacted with inorganic solid supports to afford catalysts for the slurry
      phase polymerisation of ethylene. Those supported on solid polymethylaluminoxane
      were both highly active catalysts and afforded polymers with a desirable, low
      aggregation, "popcorn" morphology.

PMID- 30206625
TI  - Sequential deposition of microdroplets on patterned surfaces.
AB  - We use a combination of experiments and numerical modelling to investigate the
      influence of physico-chemical-patterned substrates on the spreading of fluid
      deposited as a partially overlapping sequence of droplets via inkjet printing.
      Our investigation is motivated by the manufacture of polymeric organic light
      emitting-diode displays, where the substrate is textured with a regular array of
      shallow recessed regions (pixels) that are highly wetting compared to the
      remainder of the substrate. We examine the roles of topography and wettability
      patterning separately and in combination. On a substrate with uniform
      wettability, we find that the presence of bounding side walls enhances the local
      spreading and facilitates fluid coverage of the entire recessed region, but
      containment within the pixel is not guaranteed. In contrast, wettability
      patterning alone leads to robust containment of the fluid within the wetting
      region, but fluid coverage is reduced in the absence of side walls. Our
      theoretical calculations use a simplified numerical model of fluid redistribution
      via purely capillary effects, augmented by a Cox-Voinov spreading law. The
      neglect of fluid viscosity in this model means that, after an initial period of
      agreement, the predicted evolution is faster than in the experiments.
      Nonetheless, the simplified model achieves excellent predictions both for the
      liquid morphologies and for the conditions required for successful pixel filling
      on substrates with topographical and wettability variations.

PMID- 30206627
TI  - Synergism between luteolin and sulforaphane in anti-inflammation.
AB  - Luteolin and sulforaphane are well-known food bioactives with anti-inflammatory
      properties. Herein, we determined their combinational effects in inhibiting
      inflammation in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Both
      luteolin and sulforaphane showed dose-dependent inhibition on LPS-induced
      production of nitric oxide (NO) in the macrophages. The combined treatments led
      to a stronger inhibition on NO production compared to the singular treatments.
      Isobologram analysis confirmed that the combined treatments produced a synergy.
      Western blotting and ELISA showed that the combined treatment reduced the
      expression levels of pro-inflammatory proteins involving NF-kappaB pathway, and
      STAT3 activation, which regulated expression of other inflammatory proteins such
      as iNOS, COX-2, IL-6, and IL-1beta. Moreover, the combination treatments reduced
      reactive oxygen species in cells and increased the expression of Nrf2 and HO-1,
      which are cellular antioxidant proteins. In conclusion, our findings support the
      notion that certain bioactive food components may act synergistically to produce
      enhanced health effects such as anti-inflammation.

PMID- 30206628
TI  - Iodine-catalyzed cross-coupling of isocyanides and thiols for the synthesis of S
      thiocarbamates.
AB  - A novel and efficient metal free, redox-neutral method for the synthesis of
      secondary thiocarbamates by cross-coupling of readily available thiophenol and
      isocyanides has been developed. The present methodology exhibits a broad
      substrate scope with good to excellent yields without an additive/extra oxidant
      under mild reaction conditions catalyzed by inexpensive iodine as the catalyst.

PMID- 30206629
TI  - Computational model of wound healing: EGF secreted by fibroblasts promotes
      delayed re-epithelialization of epithelial keratinocytes.
AB  - It is widely agreed that keratinocyte migration plays a crucial role in wound re
      epithelialization. Defects in this function contribute to wound reoccurrence
      causing significant clinical problems. Several in vitro studies have shown that
      the speed of migrating keratinocytes can be regulated by epidermal growth factor
      (EGF) which affects keratinocyte's integrin expression. The relationship between
      integrin expression (through cell-matrix adhesion) stimulated by EGF and
      keratinocyte migration speed is not linear since increased adhesion, due to
      increased integrin expression, has been experimentally shown to slow down cell
      migration due to the biphasic dependence of cell speed on adhesion. In our
      previous work we showed that keratinocytes that were co-cultured with EGF
      enhanced fibroblasts formed an asymmetric migration pattern, where, the
      cumulative distances of keratinocytes migrating toward fibroblasts were smaller
      than those migrating away from fibroblasts. This asymmetric pattern is thought to
      be provoked by high EGF concentration secreted by fibroblasts. The EGF stimulates
      the expression of integrin receptors on the surface of keratinocytes migrating
      toward fibroblasts via paracrine signaling. In this paper, we present a
      computational model of keratinocyte migration that is controlled by EGF secreted
      by fibroblasts using the Cellular Potts Model (CPM). Our computational simulation
      results confirm the asymmetric pattern observed in experiments. These results
      provide a deeper insight into our understanding of the complexity of keratinocyte
      migration in the presence of growth factor gradients and may explain re
      epithelialization failure in impaired wound healing.

PMID- 30206630
TI  - Selenium deficiency induces duodenal villi cell apoptosis via an oxidative stress
      induced mitochondrial apoptosis pathway and an inflammatory signaling-induced
      death receptor pathway.
AB  - Selenium (Se) is an important nutritional trace element possessing antioxidant
      properties. Our goal was to elucidate the effect and mechanism of Se deficiency
      on the intestinal cell fate. One-day-old three-yellow chickens were fed a low Se
      diet for 1, 3, and 5 weeks. Histologic characteristics, protein expression
      profiles, antioxidant activities, inflammatory signaling, and the apoptosis
      status in duodenum mucosa were investigated. Histological results showed that Se
      deficiency could increase inflammatory cell infiltration, karyopyknosis of the
      epithelial cells, cytoplasm vacuolization and dissolution of goblet cells. The
      proteomics results indicated that Se deficiency could induce apoptosis of cells
      in duodenal villi via inhibition of antioxidant redox signaling and activation of
      NF-kappaB signaling. Further analysis results showed that Se deficiency decreased
      the total antioxidant capacity of duodenum mucosa via down-regulating the
      transcription level and activities of glutathione peroxidase (GPX), reduced
      glutathione (GSH), and thioredoxin reductase (TrxR). The NF-kappaB signaling
      pathway was activated by Se deficiency-induced reactive oxygen species (ROS).
      TUNEL, DNA ladder, immunohistochemical assay, and western blotting proved that
      selenium deficiency could induce duodenal villi cell apoptosis. The results also
      indicated that Se deficiency can cause duodenal villi cell apoptosis via an
      oxidative stress-induced mitochondrial apoptosis pathway (intrinsic pathway) and
      an inflammatory signaling-induced death receptor pathway (extrinsic pathway). Our
      data may provide new insight into the prevention and treatment of chronic
      diarrhea caused by Se deficiency.

PMID- 30206631
TI  - An effective preparation of both 1,3-diketones and nitriles from alkynones with
      oximes as hydroxide sources.
AB  - An effective phosphine-catalyzed protocol has been established for the syntheses
      of 1,3-diketones and nitriles from alkynones with oximes as hydroxide surrogates.
      This method features the use of a phosphine catalyst, compatibility with various
      functional groups and ambient temperature, which makes this approach very
      practical. A plausible mechanism was proposed.

PMID- 30206632
TI  - The inhibitory role of intracellular free zinc in the regulation of Arg-1
      expression in interleukin-4-induced activation of M2 microglia.
AB  - Microglia, the resident immune cells of the central nervous system, can display a
      pro-inflammatory M1 phenotype or an anti-inflammatory M2 phenotype. Arginase
      (Arg)-1 expressed in interleukin-4 (IL-4)-induced M2 microglia reduces nitric
      oxide (NO) production by competing with inducible NO synthase for l-arginine,
      which contributes to the attenuation of brain inflammation. Although previous
      studies have indicated that brain zinc promotes M1 activation, the effect of zinc
      on M2 microglial activation remains to be determined. In the present study,
      murine primary microglia treated with 10 ng mL-1 IL-4 exhibited increased Arg-1
      mRNA expression and levels of intracellular free zinc. Chelation of this
      increased intracellular free zinc by the cell permeable zinc chelator N,N,N',N'
      tetrakis-(2-pyridylmethyl)ethylenediamine (TPEN) aggravated the IL-4-induced mRNA
      expression and enzymatic activity of Arg-1. However, the cell impermeable zinc
      chelator CaEDTA had no effect on Arg-1 expression or cytosolic levels of free
      zinc in IL-4-induced M2-polarized microglia. Furthermore, treatment with IL-4
      resulted in upregulation of phagocytic activity in microglia, while
      administration of TPEN abolished IL-4-induced phagocytic activity. Moreover, this
      effect was reversed vial-arginine supplementation. These findings suggest that IL
      4 induces an increase in intracellular free zinc in microglia, which may act as a
      negative regulator of IL-4-induced Arg-1 expression, and that such negative
      regulation is essential for microglial phagocytic activity.

PMID- 30206633
TI  - An ATP-fueled nucleic acid signal amplification strategy for highly sensitive
      microRNA detection.
AB  - Herein, an adenosine triphosphate (ATP)-fueled nucleic acid signal amplification
      strategy based on toehold-mediated strand displacement (TMSD) and fluorescence
      resonance energy transfer (FRET) was proposed for highly sensitive detection of
      microRNA-21. More importantly, the target microRNA-21 could be regenerated with
      ATP as the fuel rather than a nucleotide segment in conventional approaches,
      which made the proposed strategy simple and efficient due to the high affinity
      and strength of the aptamer-target interaction.

PMID- 30206620
TI  - Antimicrobial action of calprotectin that does not involve metal withholding.
AB  - Calprotectin is a potent antimicrobial that inhibits the growth of pathogens by
      tightly binding transition metals such as Mn and Zn, thereby preventing their
      uptake and utilization by invading microbes. At sites of infection, calprotectin
      is abundantly released from neutrophils, but calprotectin is also present in non
      neutrophil cell types that may be relevant to infections. We show here that in
      patients infected with the Lyme disease pathogen Borreliella (Borrelia)
      burgdorferi, calprotectin is produced in neutrophil-free regions of the skin, in
      both epidermal keratinocytes and in immune cells infiltrating the dermis,
      including CD68 positive macrophages. In culture, B. burgdorferi's growth is
      inhibited by calprotectin, but surprisingly, the mechanism does not involve the
      classical withholding of metal nutrients. B. burgdorferi cells exposed to
      calprotectin cease growth with no reduction in intracellular Mn and no loss in
      activity of Mn enzymes including the SodA superoxide dismutase. Additionally,
      there is no obvious loss in intracellular Zn. Rather than metal depletion, we
      find that calprotectin inhibits B. burgdorferi growth through a mechanism that
      requires physical association of calprotectin with the bacteria. By comparison,
      calprotectin inhibited E. coli growth without physically interacting with the
      microbe, and calprotectin effectively depleted E. coli of intracellular Mn and
      Zn. Our studies with B. burgdorferi demonstrate that the antimicrobial capacity
      of calprotectin is complex and extends well beyond simple withholding of metal
      micronutrients.

PMID- 30206635
TI  - Adverse Sexual Effects of Treatment with Finasteride or Dutasteride for Male
      Androgenetic Alopecia: A Systematic Review and Meta-analysis.
AB  - Treatment of male androgenetic alopecia with 5alpha-reductase inhibitors is
      efficacious. However, the risk of adverse sexual effects remains controversial.
      This systematic review and meta-analysis investigated the risk of adverse sexual
      effects due to treatment of androgenetic alopecia in male patients with
      finasteride, 1 mg/day, or dutasteride, 0.5 mg/day. Fifteen randomized double
      blinded placebo-controlled trials (4,495 subjects) were meta-analysed. Use of
      5alpha-reductase inhibitors carried a 1.57-fold risk of sexual dysfunction (95%
      confidence interval (95% CI) 1.19-2.08). The relative risk was 1.66 (95% CI 1.20
      2.30) for finasteride and 1.37 (95% CI 0.81-2.32) for dutasteride. Both drugs
      were associated with an increased risk, although the increase was not
      statistically significant for dutasteride. As studies into dutasteride were
      limited, further trials are required. It is important that physicians' are aware
      of, and assess, the possibility of sexual dysfunction in patients treated with
      5alpha-reductase inhibitors.

PMID- 30206636
TI  - Bizarre Pigmented Lesion on the Scalp: A Quiz.

PMID- 30206637
TI  - Predatory Journals in Dermatology: A Hidden Danger.

PMID- 30206638
TI  - Nail Involvement as a Predictor of Disease Severity in Paediatric Psoriasis:
      Follow-up Data from the Dutch ChildCAPTURE Registry.
AB  - Little is known about the relationship between nail psoriasis and psoriasis
      severity in children, and there has been no longitudinal assessment of psoriasis
      severity related to nail psoriasis. The aim of this study was to assess whether
      nail psoriasis could serve as a predictor for a more severe disease course. De
      identified data were obtained from the Child-CAPTURE registry, a daily clinical
      practice cohort of children with psoriasis, from September 2008 to November 2015.
      Cross-sectional analyses were performed at baseline. Longitudinal data until 2
      year follow-up were analysed by linear mixed models. Nail psoriasis was present
      in 19.0% of all 343 patients at baseline and cross-sectionally associated with
      higher Psoriasis Area and Severity Index (PASI) (p = 0.033). Longitudinal
      analysis demonstrated higher PASI (p < 0.001) during 2-year follow-up in patients
      with nail involvement at baseline. These findings suggest that nail psoriasis is
      a potential clinical predictor for more severe disease course over time in
      paediatric psoriasis.

PMID- 30206639
TI  - Knowledge and Influence of Predatory Journals in Dermatology: A Pan-Austrian
      Survey.
AB  - The aim of this study was to assess the knowledge and influence of predatory
      journals in the field of dermatology in Austria. A total of 286 physicians (50.5%
      men) completed a questionnaire. The vast majority of subjects read scientific
      articles (n = 281, 98.3%) and took them into consideration in their clinical
      decision-making (n = 271, 98.5% of participants that regularly read scientific
      literature). Open access was known by 161 (56.3%), predatory journals by 84
      (29.4%), and the Beall's list by 19 physicians (6.7%). A total of 117
      participants (40.9%) had been challenged by patients with results from the
      scientific literature, including 9 predatory papers. Participants who knew of
      predatory journals had a higher level of education as well as scientific
      experience, and were more familiar with the open-access system (p < 0.001). These
      results indicate that the majority of dermatologists are not familiar with
      predatory journals. This is particularly the case for physicians in training and
      in the early stages of their career.

PMID- 30206640
TI  - Transcriptional effects of actin-binding compounds: the cytoplasm sets the tone.
AB  - Actin has emerged as a versatile regulator of gene transcription. Cytoplasmatic
      actin regulates mechanosensitive-signaling pathways such as MRTF-SRF and Hippo
      YAP/TAZ. In the nucleus, both polymerized and monomeric actin directly interfere
      with transcription-associated molecular machineries. Natural actin-binding
      compounds are frequently used tools to study actin-related processes in cell
      biology. However, their influence on transcriptional regulation and intranuclear
      actin polymerization is poorly understood to date. Here, we analyze the effects
      of two representative actin-binding compounds, Miuraenamide A (polymerizing
      properties) and Latrunculin B (depolymerizing properties), on transcriptional
      regulation in primary cells. We find that actin stabilizing and destabilizing
      compounds inversely shift nuclear actin levels without a direct influence on
      polymerization state and intranuclear aspects of transcriptional regulation.
      Furthermore, we identify Miuraenamide A as a potent inducer of G-actin-dependent
      SRF target gene expression. In contrast, the F-actin-regulated Hippo-YAP/TAZ axis
      remains largely unaffected by compound-induced actin aggregation. This is due to
      the inability of AMOTp130 to bind to the amorphous actin aggregates resulting
      from treatment with miuraenamide. We conclude that actin-binding compounds
      predominantly regulate transcription via their influence on cytoplasmatic G-actin
      levels, while transcriptional processes relying on intranuclear actin
      polymerization or functional F-actin networks are not targeted by these compounds
      at tolerable doses.

PMID- 30206641
TI  - Integrin and microtubule crosstalk in the regulation of cellular processes.
AB  - Integrins engage components of the extracellular matrix, and in collaboration
      with other receptors, regulate signaling cascades that impact cell behavior in
      part by modulating the cell's cytoskeleton. Integrins have long been known to
      function together with the actin cytoskeleton to promote cell adhesion,
      migration, and invasion, and with the intermediate filament cytoskeleton to
      mediate the strong adhesion needed for the maintenance and integrity of
      epithelial tissues. Recent studies have shed light on the crosstalk between
      integrin and the microtubule cytoskeleton. Integrins promote microtubule
      nucleation, growth, and stabilization at the cell cortex, whereas microtubules
      regulate integrin activity and remodeling of adhesion sites. Integrin-dependent
      stabilization of microtubules at the cell cortex is critical to the establishment
      of apical-basal polarity required for the formation of epithelial tissues. During
      cell migration, integrin-dependent microtubule stabilization contributes to front
      rear polarity, whereas microtubules promote the turnover of integrin-mediated
      adhesions. This review focuses on this interdependent relationship and its impact
      on cell behavior and function.

PMID- 30206642
TI  - [Transport of ventilated emergency patients from the air rescue service to the
      hospital destination (HOVER study) : Results of an online survey].
AB  - BACKGROUND: In Germany more than 110,000 helicopter emergency medical service
      (HEMS) missions are carried out annually. A considerable number of patients are
      ventilated during the flight. So far, structured surveys with respect to the
      ground transport from the helipad to the hospital facility and handover of
      ventilated patients in the emergency room (ER) are not available in the German
      speaking HEMS system. The handover of ventilated HEMS patients in the ER (HOVER I
      study) explored the use of the helicopter ventilator and medical equipment during
      the transport from the hospital landing site to the ER. METHOD: After approval by
      the HEMS operators, emergency medical doctors and HEMS technical crew members
      (HEMS-TC) of 145 German-speaking HEMS bases were invited to participate in an
      anonymous online survey (period: 1 February 2018-1 March 2018). Each participant
      was only allowed to submit the survey once. RESULTS: Data of 569 participants
      were completely analyzed, with responses from 429 emergency physicians and 140
      HEMS-TC (75% from Germany, 13% Switzerland, 11% Austria, 1% Italy and
      Luxembourg). The most frequent type of aircraft used was the Eurocopter
      (EC)/Airbus helicopter (H) 135 (60.5%) followed by the EC/H 145 (33%). The
      majority of the respondents (53%) principally used the helicopter ventilator
      machine for patient transport from the helipad to the ER, 38% used it depending
      on the circumstances and 7% never used it. Of the participants 52% always took
      the emergency backpack for patient transport to the ER, 43% depending on the
      situation and 5% never took it along. The availability of oxygen or a ventilator
      at the helipad was considered to be helpful (59% and 45%, respectively),
      obligatory (25% and 14%, respectively) but was also considered unnecessary by
      some participants (16% and 40%, respectively). The collection of the HEMS team by
      a hospital team at the helipad was rated as helpful (64%) or mandatory (19%), 12%
      considered it to be unimportant and 5% even disturbing. For most respondents
      (58.5%) the responsibility for the patient ended after a structured handover on
      reaching the internal hospital target area (e.g. the ER). CONCLUSION: The
      management of the handover of ventilated emergency patients in German-speaking
      HEMS is heterogeneously structured. Only approximately 50% of the participants
      frequently carried the helicopter ventilator and emergency equipment during
      patient transport to the ER. Depending on the situation, more than 90% of the
      respondents used the helicopter ventilator and emergency backpack during the
      transport. The collection of the HEMS team by a hospital team at the helipad was
      appreciated by the majority of participants. The use of the helicopter ventilator
      for patient transport to the ER needs to be explored in future studies. The study
      was registered at the Research Registry ( www.researchregistry.com ) under the
      following number: researchregistry2925.

PMID- 30206634
TI  - A H2O2-free depot for treating bacterial infection: localized cascade reactions
      to eradicate biofilms in vivo.
AB  - Peroxidase-like nanoparticles are promising materials to treat bacterial
      infection through catalyzing H2O2 into more toxic highly reactive oxygen species
      (hROS; such as hydroxyl radicals). However, all the reported related strategies,
      to the best of our knowledge, depend on the usage of extra H2O2, limiting the
      applications of peroxidase-like nanoparticles. Thus, it is necessary to develop
      peroxidase-based materials without extra H2O2. In this report, H2O2-free depots
      are prepared by integrating CaO2 and hemin-loading graphene (H-G) into alginate
      (CaO2/H-G@alginate). They can convert H2O into hROS through localized cascade
      reactions at the site of bacterial infection and damage the main components of
      biofilms (bacteria, polysaccharides, proteins, and nucleic acids). Besides, the
      confined environment of depots can reduce the potential risk from H2O2 and
      improve the cascade catalytic activity. This is the first example of exploring
      peroxidase-like nanozymes without extra H2O2 to treat bacterial infection.

PMID- 30206645
TI  - An Approach to Electrokinetic Removal of Cr(VI) from Soil and Kaolin Samples.
AB  - The present study examines electroremediation's efficiency on Cr(VI) contaminated
      samples. Electrokinetic experiments were performed applying a DC voltage of 30 V
      to a cylindrical sample of 30 cm length and 4 cm diameter, using Na2SO4 as
      background electrolyte solution. The first two experiments, one with kaolin and
      one with soil, were carried out without applying any pH adjustment in the anode
      or the cathode compartment, using 0.01 M Na2SO4. Further experiments were carried
      out increasing the electrolyte's concentration and using Mg(OH)2 to neutralize
      the generated acidity in the anode. The decrease in Cr(VI) concentration in the
      soil samples is partly taking place because of its reduction, most likely due to
      the presence of organic matter. This is indicated by the mass balance
      calculations which were based on the analyses of treated solid samples and
      electrolyte solutions. In the kaolin samples electromigration is the main factor
      resulting in the accumulation of Cr(VI) in the anodic solution.

PMID- 30206644
TI  - Efficacy of stereotactic body radiotherapy for unresectable or recurrent
      cholangiocarcinoma: a meta-analysis and systematic review.
AB  - PURPOSE: Non-surgical treatment including stereotactic body radiation therapy
      (SBRT) have been used practically as alternative modalities for unresectable or
      recurrent cholangiocarcinoma (CC). We performed a systematic review and meta
      analysis to examine the efficacy of SBRT for such patients. METHODS: Embase,
      PubMed, MEDLINE, and Cochrane library databases were searched systematically
      until October 2017. Primary endpoint was 1-year local control (LC) rate; 1-year
      overall survival (OS), response rates, and grade >=3 toxicities were assessed as
      secondary endpoints. RESULTS: Eleven studies (226 patients) were included. The
      prescribed median SBRT dose was 45 (range 30-55) Gy in 3-5 fractions. The pooled
      1-year LC rate was 81.8% (95% confidence interval [CI] 69.4-89.9%) in the studies
      using an equivalent dose in 2 Gy per fraction (EQD2) >=71.3 Gy2 and 74.7% (95% CI
      57.1-86.7%) in the studies using an EQD2 <71.3 Gy2. The median OS was 13.6 (range
      10-35.5) months. The pooled 1-year OS rate was 53.8% (95% CI 44.9-62.5%) and the
      pooled 1-year LC rate was 78.6% (95% CI 69.0-85.8%). Most common toxicity was
      duodenal ulcer and gastric ulcer in available studies, with the acute incidence
      of grade >=3 of less than 10% and the late incidence of 10-20%. CONCLUSIONS: SBRT
      was a feasible treatment option with respect to achieving a high LC for
      unresectable or recurrent CC. Gastrointestinal toxicity is acceptable, but
      remains an obstacle related to dose escalation.

PMID- 30206646
TI  - Transplanted Moss Hylocomium splendens as a Bioaccumulator of Trace Elements from
      Different Categories of Sampling Sites in the Upper Silesia Area (SW Poland):
      Bulk and Dry Deposition Impact.
AB  - Concentrations of Cd, Co, Cr, Cu, Ni, K, Fe, Mn, Pb, V and Zn in transplants of
      Hylocomium splendens (Hedw.) Schimp. were compared with bulk deposition and dust
      samples from three different categories of sites: industrial, residential and
      their surroundings and rural (15 in total). Mosses were transplanted for 90 days
      to severely polluted areas of Upper Silesia, and samples of precipitation and
      dust were collected during the same period. Most of the significant correlations
      between element concentrations in mosses and bulk deposition (Cd, Ni, Pb and Zn)
      were found for industrial sites. In this study dry deposition carried higher
      element concentrations than bulk deposition, which may result in the higher
      passive capture of particulate matter by mosses.

PMID- 30206650
TI  - Post-buckling behaviour of a growing elastic rod.
AB  - We consider mechanically-induced pattern formation within the framework of a
      growing, planar, elastic rod attached to an elastic foundation. Through a
      combination of weakly nonlinear analysis and numerical methods, we identify how
      the shape and type of buckling (super- or subcritical) depend on material
      parameters, and a complex phase-space of transition from super- to subcritical is
      uncovered. We then examine the effect of heterogeneity on buckling and post
      buckling behaviour, in the context of a heterogeneous substrate adhesion, elastic
      stiffness, or growth. We show how the same functional form of heterogeneity in
      different properties is manifest in a vastly differing post-buckled shape.
      Finally, a fourth form of heterogeneity, an imperfect foundation, is incorporated
      and shown to have a more dramatic impact on the buckling instability, a
      difference that can be qualitatively understood via the weakly nonlinear
      analysis.

PMID- 30206652
TI  - [Gottfried Geiler : December 13, 1927-April 28, 2018].

PMID- 30206647
TI  - ERG Channels Regulate Excitability in Stellate and Bushy Cells of Mice Ventral
      Cochlear Nucleus.
AB  - ERG (ether-a-go-go-related gene) channels are the members of the voltage
      dependent potassium channel family, which have three subtypes, as ERG1 (Kv 11.1),
      ERG2 (Kv 11.2), and ERG3 (Kv11.3). There is no information on ERG channels in the
      cochlear nucleus (CN) neurons, which is the first relay station of the auditory
      pathway. As occur in some of congenital long QT Syndromes (LQTS), mutation of the
      KCNQ11 genes for ERG channel has been reported to be accompanied by hearing loss.
      For that reason, we aimed to study biophysical properties and physiological
      importance, and contribution of ERG K+ currents to the formation of action
      potentials in the stellate and bushy neurons of the ventral cochlear nucleus
      (VCN). A total of 70 mice at 14-17 days old were used for this study.
      Electrophysiological characterization of ERG channels was performed using patch
      clamp technique in the CN slices. In current clamp, ERG channel blockers,
      terfenadine (10 uM) and E-4031 (10 uM), were applied in both cell types. The
      activation, inactivation, and deactivation kinetics of the ERG channels were
      determined by voltage clamp. In conclusion, the findings obtained in the present
      study suggest that stellate and bushy neurons express ERG channels and ERG
      channels appear to contribute to setting action potential (AP) frequency,
      threshold for AP induction, and, possibly, resting membrane potentials in this
      cells.

PMID- 30206648
TI  - Efficacy and Safety of Botulinum Toxin Type A Injection in Patients with
      Bilateral Trapezius Hypertrophy.
AB  - OBJECTIVE: To evaluate aesthetic outcomes in patients with bilateral trapezius
      hypertrophy treated by botulinum toxin type A (BTxA) injection for aesthetic
      reconstruction of the upper trapezius. METHODS: From May 2015 to May 2016, 30
      women with a short neck shape resulting from bilateral trapezius hypertrophy were
      treated with botulinum toxin type A (BTxA) injection at the most affected area of
      the upper trapezius. Pre- and postoperative values of SACDF (irregularly shaped
      area of the four points A, C, D, and F) and SACDE (irregularly shaped area of the
      four points A, C, D, and E), responses to patients' and doctors' Global Aesthetic
      Improvement Scale (GAIS) questionnaires for neck aesthetic assessment, as well as
      reported adverse events, were recorded and analyzed. RESULTS: Duration of follow
      up ranged from 4 to 12 months. Subjects experienced non-severe adverse events and
      complete recovery after a single BTxA injection. In patients' GAIS
      questionnaires, "very much improved" accounted for 53%, "much improved" accounted
      for 13%, and "improved" accounted for 27%. In doctors' GAIS questionnaires, "very
      much improved" accounted for 27%, "much improved" accounted for 33%, "improved"
      accounted for 33%, and "no change" accounted for 7%. The overall degree of
      improvement was high. Statistically significant differences were observed with
      respect to the "very much improved" response to GAIS questionnaires between
      patients and doctors (P = 0.035). CONCLUSION: A single injection of BTxA for
      aesthetic reconstruction of the upper trapezius is safe and effective in patients
      with bilateral trapezius hypertrophy. 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- 30206653
TI  - [Identification of diagnostic tumour markers and therapeutic targets in
      testicular tumours].
AB  - Today, tumour classification has been expanded due to immunohistochemical and
      molecular-pathological analyses due to corresponding patterns/profiles of protein
      and gene expression. The latter analyses often include growth factors and their
      ligands, intracellular signalling pathways, DNA-binding proteins, and oncogenes
      and suppressor genes, thus functionally including primarily the regulation of
      growth including angiogenesis and apoptosis as well as the induction of
      metastases to adhesion and migration disorders. Based on observations that
      testicular tumours often show microcalcifications, possibly due to impaired
      calcium metabolism, we focused on calcium-dependent transmembrane proteins,
      particularly cadherins, in the search for new tumour markers and therapeutic
      targets. N-cadherin is expressed differently in the various subtypes of germ cell
      tumours and is useful in N-cadherin-positive germ cell tumours as a novel
      therapeutic targeting structure, particularly in cisplatin resistance, due to
      functional analysis. In the tumours of the sex cord stroma beta-catenin and the
      transcription factor SOX-9 give a clear classification of these tumours. Thus,
      morphological investigations prove to be pilot experiments to purposefully narrow
      the spectrum of functionally important proteins and thus to establish promising
      new differential diagnostic markers or target structures.

PMID- 30206654
TI  - [YAP induces chromosomal instability in liver cancer patients].
AB  - BACKGROUND: The Hippo/YAP signaling pathway is a central regulator of organ
      growth and cell proliferation. Activation of the transcriptional co-activator and
      oncogene YAP (yes-associated protein) supports the development of liver cancer.
      AIMS: The aim of this work was to analyze the molecular mechanisms which are
      responsible for YAP-induced hepatocarcinogenesis. METHODS: YAP was silenced using
      siRNAs in liver cancer cell lines and effects on target gene expression were
      analyzed via real-time polymerase chain reaction (PCR) and western
      immunoblotting. Immunoprecipitation and chromatin immunoprecipitation was used to
      study interacting proteins and binding to target gene promoter regions,
      respectively. Transgenic mice with liver-specific and inducible YAP expression
      were used for in vivo analysis. Gene expression data from hepatocellular
      carcinoma (HCC) patients were used to analyze YAP-dependent gene signatures and
      to correlate with clinical data. HCC tissue microarrays were analyzed using
      immunohistochemistry. RESULTS: Together with the transcription factors TEAD4 and
      FOXM1, YAP induces the expression of genes which are responsible for the
      development of chromosomal instability (CIN). The overexpression of these CIN
      genes characterizes liver cancer patients with a poor prognosis. Mechanistically,
      YAP/TEAD4 and FOXM1 bind to the promoter regions of the CIN genes to directly
      regulate their expression. The treatment of YAP-transgenic mice with a specific
      FOXM1 inhibitor reduces the YAP-dependent hepatomegaly, CIN gene expression and
      CIN. The analysis of human HCC tissue samples confirms the statistical
      correlation between YAP, FOXM1 and CIN. DISCUSSION: These results reveal a new
      oncogenic mechanism of the Hippo/YAP signaling pathway and identify YAP and FOXM1
      as potential targets for targeted therapies.

PMID- 30206657
TI  - "Partial extensor mechanism allograft reconstruction for chronic patellar tendon
      disruption shows superior outcomes in native knees when compared to same
      technique following total arthroplasty": several questions.

PMID- 30206655
TI  - A simple method for bone graft insertion during Schatzker II and III plateau
      fixation.
AB  - Insertion of bone graft to fill metaphyseal defects and supply subchondral
      support when fixing Schatzker type II and III tibial plateau fractures can be
      difficult and tedious. Accurately directing the placement of bone graft through a
      small entry portal and against gravity can be challenging. Using a modified 3-mL
      syringe and bone tamps with application of the Seldinger technique can make this
      tedious task simple and more accurate. Level of evidence V.

PMID- 30206656
TI  - Effect of canagliflozin, a sodium glucose co-transporter 2 inhibitor, on
      cisplatin-induced nephrotoxicity in mice.
AB  - Canagliflozin is a sodium glucose co-transporter 2 (SGLT2) inhibitor that is
      currently available for the management of type 2 diabetes mellitus. The present
      study investigated the effect of canagliflozin on cisplatin (CP)-induced
      nephrotoxicity in mice. The animals were divided into four groups (n = 6). The
      first and second groups received normal saline (control) and intraperitoneal
      (i.p.) cisplatin (20 mg/kg) on day 7, respectively. The third and fourth groups
      were given a single intraperitoneal (i.p.) injection of CP (20 mg/kg) on day 7
      and canagliflozin (10 mg/kg/day) and (30 mg/kg/day), for 10 days, respectively.
      At day 11, animals were anesthetized and blood collected and kidneys were
      removed. CP significantly increased the plasma urea, creatinine, cystatin C, and
      clusterin concentrations and neutrophil gelatinase-associated lipocalin (NGAL)
      activity. In addition, CP increased urinary albumin/creatinine ratio, N-acetyl
      beta-D-glucosaminidase (NAG) activity, and liver-type fatty acid-binding protein
      (L-FABP) concentrations and reduced creatinine clearance. CP also significantly
      increased the plasma concentration of inflammatory cytokines [plasma tumor
      necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin-1beta
      (IL-1beta)] and significantly reduced antioxidant indices [catalase, glutathione
      reductase (GR), and superoxide dismutase (SOD)]. Histopathologically, CP caused a
      remarkable renal damage compared with control. Canagliflozin significantly
      ameliorated CP-induced biochemical and histopathological changes. The protective
      effect of canagliflozin is most likely due to anti-inflammatory and antioxidant
      effects. Our results show that administration of canagliflozin reversed the
      biochemical and histopathological indices of CP-induced nephrotoxicity in mice.

PMID- 30206659
TI  - Bisphosphonate therapy in an infant with generalized arterial calcification with
      an ABCC6 mutation.
AB  - Generalized arterial calcification of infancy (GACI) is a rare genetic disorder
      with high infantile mortality, described to be due to ENPP1, and less commonly
      ABCC6 mutations. Bisphosphonate treatment has been described to improve survival
      in ENPP1-positive GACI patients, but few studies have described bisphosphonate
      treatment in ABCC6-positive patients. Without therapy, patients will die before 6
      months of age. Our patient is now 3 years old, former recipient twin of twin-to
      twin transfusion syndrome (TTTS). Initial fetal echocardiogram at 19 weeks showed
      calcifications of the ascending aorta and pulmonary artery (PA). She underwent
      utero laser therapy, and despite resolution of the TTTS, her follow-up scans
      showed progressive calcification of the aorta and PA. Postnatal echocardiogram
      showed calcification and supravalvar stenosis of the aorta and PA. CT on day of
      life 6 showed calcifications in the PAs, aortic arch, and descending aorta.
      Quantification of valvular calcification can be difficult; in our patient,
      increasing outflow tract gradient on echocardiogram was used to monitor disease
      progression. Molecular testing revealed an ABCC6 gene mutation. She was started
      on weekly IV pamidronate (0.1-0.3 mg/kg/week) on day 8 of life then transitioned
      to oral etidronate (15-20 mg/kg/day). Given progressive supravalvar aortic and
      pulmonary stenosis, she underwent surgical repair with patch augmentation of the
      PA and ascending aorta at 4 months old. She has done well post-operatively,
      continuing on enteral bisphosphonate therapy with no side effects to date. Her
      identical twin was confirmed to have the same mutation and remains asymptomatic
      with no calcifications. Aggressive bisphosphonate therapy should be started as
      soon as possible in patients with infantile arterial calcinosis due to ABCC6 or
      ENPP1 mutations. Echocardiographic evaluation can be used to monitor disease
      progression by arterial gradients. Molecular testing is also essential to
      evaluate for possible co-morbidities in these patients and pregnancy management
      for the future.

PMID- 30206660
TI  - Identification and characterization of Delta12 and Delta12/Delta15 bifunctional
      fatty acid desaturases in the oleaginous yeast Lipomyces starkeyi.
AB  - Fatty acid desaturases play vital roles in the synthesis of unsaturated fatty
      acids. In this study, Delta12 and Delta12/Delta15 fatty acid desaturases of the
      oleaginous yeast Lipomyces starkeyi, termed LsFad2 and LsFad3, respectively, were
      identified and characterized. Saccharomyces cerevisiae expressing LsFAD2
      converted oleic acid (C18:1) to linoleic acid (C18:2), while a strain of LsFAD3
      expressing S. cerevisiae converted oleic acid to linoleic acid, and linoleic acid
      to alpha-linolenic acid (C18:3), indicating that LsFad2 and LsFad3 were Delta12
      and bifunctional Delta12/Delta15 fatty acid desaturases, respectively. The
      overexpression of LsFAD2 in L. starkeyi caused an accumulation of linoleic acid
      and a reduction in oleic acid levels. In contrast, overexpression of LsFAD3
      induced the production of alpha-linolenic acid. Deletion of LsFAD2 and LsFAD3
      induced the accumulation of oleic acid and linoleic acid, respectively. Our
      findings are significant for the commercial production of polyunsaturated fatty
      acids, such as omega-3 polyunsaturated fatty acids, in L. starkeyi.

PMID- 30206658
TI  - Gender differences in doxorubicin pharmacology for subjects with chemosensitive
      cancers of young adulthood.
AB  - PURPOSE: For many cancers, adolescents and young adults (AYA) have worse outcomes
      than for children and adults. Many factors may contribute to the AYA survival
      gap, including differences in biology, therapeutic intent, and adherence to
      therapy. It has been observed that male AYAs have poorer outcomes than females.
      The purpose of this work was to test the proposition that gender-related
      pharmacologic factors may account for a component of the AYA survival gap.
      PATIENTS AND METHODS: A prospective, multi-institutional pharmacologic study of
      79 patients in total with chemosensitive cancers (Ewing sarcoma, osteosarcoma and
      Hodgkin lymphoma) was conducted, with conventional doxorubicin treatment.
      Pharmacokinetic data of 13 children, 40 AYAs and 13 adults were valid for
      analysis. Population pharmacokinetics models were developed for doxorubicin and
      its metabolite doxorubicinol based on the data created in this study.
      Consequently, model-based analysis was conducted to investigate the relevant
      topics. RESULTS: The clearance of doxorubicinol (normalized to body surface
      area), the main active metabolite of doxorubicin, appears faster in male AYAs
      than female (p = 0.04, 95% CI 0.1-3.9 L/h). The exposure of doxorubicinol
      (normalized to dose) is lower in male AYA than female (p = 0.03, 95% CI - 0.005
      to - 0.0002 h/L). These might be correlated to the observed difference on nadir
      neutrophil count between male AYA and female (p = 0.027, 95% CI 0.09-1.4).
      CONCLUSION: Gender-related differences in doxorubicin pharmacology may account
      for worse outcomes for male AYAs with chemosensitive cancers compared to females.
      These findings may reduce the AYA survival gap compared to other age groups.

PMID- 30206643
TI  - Conflicts of interest in infection prevention and control research: no smoke
      without fire. A narrative review.
AB  - Conflicts of interest (COIs) do occur in healthcare research, yet their impact on
      research in the field of infection prevention and control (IPC) is unknown. We
      conducted a narrative review aiming to identify examples of COIs in IPC research.
      In addition to well-known instances, we conducted PubMed and Google searches to
      identify and report case studies of COIs in IPC and antimicrobial resistance
      (AMR), which were chosen arbitrarily following consensus meetings, to illustrate
      different types of COIs. We also searched the Retraction Watch database and blog
      to systematically identify retracted IPC and/or infectious disease-related
      papers. Our review highlights COIs in academic research linked to ties between
      industry and physicians, journal editors, peer-reviewed journals' choice for
      publication, and guideline committees participants and authors. It explores how
      COIs can affect research and could be managed. We also present several selected
      case studies that involve (1) the chlorhexidine industry and how it has used
      marketing trials and key opinion leaders to promote off-label use of its
      products; (2) the copper industry and how reporting of its trials in IPC have
      furthered their agenda; (3) the influence of a company developing "closed
      infusion systems" for catheters and how this affects networks in low- and middle
      income countries and guideline development; (4) potential perverse incentives
      hospitals may have in reporting healthcare-associated infection or AMR rates and
      how government intervention may restrict AMR research for fear of bad publicity
      and subsequent negative economic consequences. Finally, the analysis of reasons
      for the retraction of previously published papers highlights the fact that
      misconduct in research may have other motivations than financial gain, the most
      visible form of COIs. COIs occur in the field of research in general, and IPC and
      AMR are no exceptions. Their effects pervade all aspects of the research and
      publication processes. We believe that, in addition to improvements in management
      strategies of COIs, increased public funding should be available to decrease
      researchers' dependency on industry ties. Further research is needed on COIs and
      their management.

PMID- 30206662
TI  - PBDE-47 and PBDE mixture (DE-71) toxicities and liver transcriptomic changes at
      PND 22 after in utero/postnatal exposure in the rat.
AB  - Pentabromodiphenyl ethers (PBDE) are found in human tissue, in household dust,
      and in the environment, and a particular concern is the potential for the
      induction of cancer pathways from these fat-soluble persistent organic
      pollutants. Only one PBDE cancer study has been conducted and that was for a PBDE
      mixture (DE-71). Because it is not feasible to test all PBDE congeners in the
      environment for cancer potential, it is important to develop a set of biological
      endpoints that can be used in short-term toxicity studies to predict disease
      outcome after long-term exposures. In this study, PBDE-47 was selected as the
      test PBDE congener to evaluate and compare toxicity to that of the carcinogenic
      PBDE mixture. The toxicities of PBDE-47 and the PBDE mixture were evaluated at
      PND 22 in Wistar Han rat (Crl: WI (Han)) pups after in utero/postnatal exposure
      (0, 0.1, 15, or 50 mg/kg; dams, GD6-21; pups, PND 12-PND 21; oral gavage daily
      dosing). By PND 22, PBDE-47 caused centrilobular hypertrophy and fatty change in
      liver, and reduced serum thyroxin (T4) levels; similar effects were also observed
      after PBDE mixture exposure. Transcriptomic changes in the liver included
      induction of cytochrome p450 transcripts and up-regulation of Nrf2 antioxidant
      pathway transcripts and ABC membrane transport transcripts. Decreases in other
      transport transcripts (ABCG5 & 8) provided a plausible mechanism for lipid
      accumulation, characterized by a treatment-related liver fatty change after PBDE
      47 and PBDE mixture exposure. The benchmark dose calculation based on liver
      transcriptomic data was generally lower for PBDE-47 than for the PBDE mixture.
      The up-regulation of the Nrf2 antioxidant pathway and changes in metabolic
      transcripts after PBDE-47 and PBDE mixture exposure suggest that PBDE-47, like
      the PBDE mixture (NTP 2016, TR 589), could be a liver toxin/carcinogen after long
      term exposure.

PMID- 30206651
TI  - NLRP3 inflammasome in colitis and colitis-associated colorectal cancer.
AB  - A low level of inflammation is an integral part of the balance between the immune
      system and the microbiota in the high antigen environment of the gastrointestinal
      tract and maintains homeostasis. A failure of this balance can lead to chronic
      intestinal inflammation and increase the chances to develop colorectal cancer
      significantly. The underlying mechanisms that link inflammation and
      carcinogenesis are not clear but the molecular platforms of the inflammasomes
      have been implicated. Inflammasomes are molecule complexes that are assembled in
      response to microbial components or cellular danger signals and facilitate the
      production of bioactive pro-inflammatory cytokines. One inflammasome in
      particular, NLRP3, has been analysed extensively in its contribution to colitis
      and has been shown to be associated with the development of colitis-associated
      colorectal cancer. This review will summarise the role of NLRP3 in intestinal
      inflammation, discuss some of the triggers of inflammation in the
      gastrointestinal tract such as diet and introduce some opportunities to use this
      inflammasome as therapeutic target for the treatment of colitis and colitis
      associated colorectal cancer.

PMID- 30206664
TI  - Correction to: Dual contributions of noradrenaline to behavioural flexibility and
      motivation.
AB  - The article Dual contributions of noradrenaline to behavioural flexibility and
      motivation written by Caroline I. Jahn, Sophie Gilardeau, Chiara Varazzani,
      Bastien Blain, Jerome Sallet, Mark E. Walton, Sebastien Bouret was originally
      published electronically on the publisher's internet portal.

PMID- 30206665
TI  - Quantification of BSA-loaded chitosan/oligonucleotide nanoparticles using reverse
      phase high-performance liquid chromatography.
AB  - Therapeutic proteins are administered subcutaneously because of their instability
      in the gastrointestinal tract. Current research suggests that polymeric-based
      nanoparticles, microparticles and liposomes are ideal nanocarriers to encapsulate
      proteins for disease management. In order to develop a successful drug delivery
      system, it is crucial to determine drug release profile and stability. However,
      the non-active excipients in polymeric formulations can influence the
      quantification of proteins in analytical techniques. This study investigated the
      effect of nine common polymers on quantification of bovine serum albumin (BSA)
      using RP-HPLC method. The technique offers advantages such as short analytical
      time, high accuracy and selectivity. In the meantime, the technique can be
      employed to separate proteins including BSA, insulin and pigment epithelium
      derived factor (PEDF). Furthermore, the RP-HPLC method was applied to quantify
      the drug release pattern of a novel BSA-loaded nanoparticulate formulation in
      simulated gastric and intestinal fluids. The nanoparticles were formulated by
      natural polymer (chitosan) and oligonucleotide (Dz13Scr) using complex
      coacervation. The prepared particles were found to have small size (337.87 nm),
      low polydispersity index (0.338) and be positively charged (10.23 mV). The in
      vitro drug release patterns were characterised using the validated RP-HPLC method
      over 12 h. Graphical abstract ?.

PMID- 30206661
TI  - Pivotal role of innate myeloid cells in cerebral post-ischemic sterile
      inflammation.
AB  - Inflammatory responses play a multifaceted role in regulating both disability and
      recovery after ischemic brain injury. In the acute phase of ischemic stroke,
      resident microglia elicit rapid inflammatory responses by the ischemic milieu.
      After disruption of the blood-brain barrier, peripheral-derived neutrophils and
      mononuclear phagocytes infiltrate into the ischemic brain. These infiltrating
      myeloid cells are activated by the endogenous alarming molecules released from
      dying brain cells. Inflammation after ischemic stroke thus typically consists of
      sterile inflammation triggered by innate immunity, which exacerbates the
      pathologies of ischemic stroke and worsens neurological prognosis. Infiltrating
      immune cells sustain the post-ischemic inflammation for several days; after this
      period, however, these cells take on a repairing function, phagocytosing
      inflammatory mediators and cellular debris. This time-specific polarization of
      immune cells in the ischemic brain is a potential novel therapeutic target. In
      this review, we summarize the current understanding of the phase-dependent role
      of innate myeloid cells in ischemic stroke and discuss the cellular and molecular
      mechanisms of their inflammatory or repairing polarization from a therapeutic
      perspective.

PMID- 30206663
TI  - Abnormal intrinsic cerebro-cerebellar functional connectivity in un-medicated
      patients with bipolar disorder and major depressive disorder.
AB  - OBJECTIVE: The cerebellum plays an important role in depression. Cerebro
      cerebellar circuits have been found to show aberrance in bipolar disorder (BD)
      and major depressive disorder (MDD). However, whether the cerebro-cerebellar
      connectivity contributes equally to the pathologic mechanisms of BD and MDD
      remains unknown. METHODS: We recruited 33 patients with MDD, 32 patients with BD,
      and 43 healthy controls (HC). We selected six seed regions (three per hemisphere)
      in the cerebrum, corresponding to the affective, cognitive control, and default
      mode networks, to establish cerebro-cerebellar functional connectivity maps.
      RESULTS: Relative to the HC, both the BD and MDD patients exhibited weaker
      negative connectivity between the right subgenual anterior cingulate cortex and
      the cerebellar vermis IV_V (pBD = 0.03, pMDD = 0.001) and weaker positive
      connectivity between the left precuneus and the left cerebellar lobule IX (pBD =
      0.043, pMDD = 0.000). Moreover, the MDD patients showed weaker positive
      connectivity in the left precuneus-left cerebellar lobule IX circuit than the BD
      patients (p = 0.049). In addition, the BD patients showed weaker positive
      connectivity in the right dorsolateral prefrontal cortex-left cerebellar lobule
      Crus Iota circuit compared to the HC (p = 0.002) or the MDD patients (p = 0.013).
      Receiver operating characteristic curves analyses showed that the altered cerebro
      cerebellar connectivities could be used to distinguish the patients from the HC
      with relatively high accuracy. CONCLUSIONS: Our findings suggested that
      differences in connectivity of cerebro-cerebellar circuits, which are involved in
      affective or cognitive functioning, significantly contributed to BD and MDD.

PMID- 30206666
TI  - Identification and Analysis of OVATE Family Members from Genome of the Early Land
      Plants Provide Insights into Evolutionary History of OFP Family and Function.
AB  - Mosses, liverworts, hornworts and lycophytes represent transition stages between
      the aquatic to terrestrial/land plants. Several morphological and adaptive
      novelties driven by genomic components including emergence and expansion of new
      or existing gene families have played a critical role during and after the
      transition, and contributed towards successful colonization of terrestrial
      ecosystems. It is crucial to decipher the evolutionary transitions and natural
      selection on the gene structure and function to understand the emergence of
      phenotypic and adaptive diversity. Plants at the "transition zone", between
      aquatic and terrestrial ecosystem, are also the most vulnerable because of
      climate change and may contain clues for successful mitigation of the challenges
      of climate change. Identification and comparative analyses of such genetic
      elements and gene families are few in mosses, liverworts, hornworts and
      lycophytes. Ovate family proteins (OFPs) are plant-specific transcriptional
      repressors and are acknowledged for their roles in important growth and
      developmental processes in land plants, and information about the functional
      aspects of OFPs in early land plants is fragmentary. As a first step towards
      addressing this gap, a comprehensive in silico analysis was carried out utilizing
      publicly available genome sequences of Marchantia polymorpha (Mp), Physcomitrella
      patens (Pp), Selaginella moellendorffii (Sm) and Sphagnum fallax (Sf). Our
      analysis led to the identification of 4 MpOFPs, 19 PpOFPs, 6 SmOFPs and 3 SfOFPs.
      Cross-genera analysis revealed a drastic change in the structure and
      physiochemical properties in OFPs suggesting functional diversification and
      genomic plasticity during the evolutionary course. Knowledge gained from this
      comparative analysis will form the framework towards deciphering and dissection
      of their developmental and adaptive role/s in early land plants and could provide
      insights into evolutionary strategies adapted by land plants.

PMID- 30206668
TI  - Insight into Bacterial Community Diversity and Monthly Fluctuations of Medicago
      sativa Rhizosphere Soil in Response to Hydrogen Gas Using Illumina High
      Throughput Sequencing.
AB  - The microbial diversity and the monthly fluctuations in Medicago sativa field
      soil in response to hydrogen gas were investigated. Illumina high-throughput
      sequencing was used to analyze the bacteria in raw and hydrogen-treated
      rhizosphere soil. Among the 18 soil samples, the abundance change of the
      predominant phyla Proteobacteria and Actinobacteria showed opposite trends. The
      diversity index analysis of the nine leguminous soil samples showed the highest
      diversity of the microbial community in July. In the other nine soil samples
      treated with hydrogen, the microbial diversity decreased and the diversity of
      soil microorganisms in September was higher than that in July, but not
      significantly so. The heat map analysis revealed that the microbial community
      composition of the soil samples was different before and after the hydrogen
      treatment. After the soil samples were treated with hydrogen, the dominant genera
      were Nocardioide, Pseudomonas, Janibacter, Microbacterium, Microvirga,
      Streptomyces, and Phenylobacterium in May; Bradyrhizobium, Haliangium,
      Sphingomonas, Blastocatella, Lysobacter, and Sphingopyxis in July; and
      Aeromicrobium, Pseudonocardia, Lentzea, and Skermanella in September. This study
      indicates that time and hydrogen gas have significant effects on the diversity of
      microbes in M. sativa rhizospheric soil.

PMID- 30206667
TI  - Three-Finger Toxin Diversification in the Venoms of Cat-Eye Snakes (Colubridae:
      Boiga).
AB  - The Asian genus Boiga (Colubridae) is among the better studied non-front-fanged
      snake lineages, because their bites have minor, but noticeable, effects on
      humans. Furthermore, B. irregularis has gained worldwide notoriety for
      successfully invading Guam and other nearby islands with drastic impacts on the
      local bird populations. One of the factors thought to allow B. irregularis to
      become such a noxious pest is irditoxin, a dimeric neurotoxin composed of two
      three-finger toxins (3FTx) joined by a covalent bond between two newly evolved
      cysteines. Irditoxin is highly toxic to diapsid (birds and reptiles) prey, but
      roughly 1000 * less potent to synapsids (mammals). Venom plays an important role
      in the ecology of all species of Boiga, but it remains unknown if any species
      besides B. irregularis produce irditoxin-like dimeric toxins. In this study, we
      use transcriptomic analyses of venom glands from five species [B. cynodon, B.
      dendrophila dendrophila, B. d. gemmicincta, B. irregularis (Brisbane population),
      B. irregularis (Sulawesi population), B. nigriceps, B. trigonata] and proteomic
      analyses of B. d. dendrophila and a representative of the sister genus
      Toxicodryas blandingii to investigate the evolutionary history of 3FTx within
      Boiga and its close relative. We found that 92.5% of Boiga 3FTx belong to a
      single clade which we refer to as denmotoxin-like because of the close relation
      between these toxins and the monomeric denmotoxin according to phylogenetic,
      sequence clustering, and protein similarity network analyses. We show for the
      first time that species beyond B. irregularis secrete 3FTx with additional
      cysteines in the same position as both the A and B subunits of irditoxin.
      Transcripts with the characteristic mutations are found in B. d. dendrophila, B.
      d. gemmicincta, B. irregularis (Brisbane population), B. irregularis (Sulawesi
      population), and B. nigriceps. These results are confirmed by proteomic analyses
      that show direct evidence of dimerization within the venom of B. d. dendrophila,
      but not T. blandingii. Our results also suggest the possibility of novel dimeric
      toxins in other genera such as Telescopus and Trimorphodon. All together, this
      suggests that the origin of these peculiar 3FTx is far earlier than was
      appreciated and their evolutionary history has been complex.

PMID- 30206670
TI  - Efficacy and safety of extending intravenous tocilizumab intervals from 4 to 6
      weeks in rheumatoid arthritis patients with good response to 4-week intervals.
AB  - A period of 4 weeks (w) has been recommended for rheumatoid arthritis (RA)
      patients as the interval between intravenous (IV) tocilizumab (TCZ, 8 mg/kg). In
      a previous paper, we showed the possibility that the interval between successive
      IV TCZ can be extended from 4 to 6 weeks in more than 60% of patients with low
      diseases activity (LDA) at 4-week intervals. Herein, we aimed to investigate the
      efficacy and safety of extending the interval from 4 to 6 weeks. A retrospective
      observational study was conducted by enrolling patients in whom the intervals of
      TCZ infusions could be extended from 4 to 6 weeks with an LDA for more than 2
      years. We compared the efficacy and side effects of TCZ infusions at intervals of
      4 and 6 weeks in a cohort of patients. We also examined serum lipid, platelet, IL
      6, and trough TCZ levels. A total of 125 patients with an LDA at 4 weeks
      intervals were enrolled in this study, of which 78 patients maintained LDA at 6
      week intervals of TCZ infusion. After extending the infusion intervals, the
      efficacy of the treatment was maintained, and the side effects decreased
      significantly. In addition, the levels of total cholesterol and triglyceride were
      returned to normal, and the serum trough levels of TCZ became undetectable at 6
      week intervals. We proved that intervals between TCZ infusions can be extended
      from 4 to 6 weeks in more than 60% of RA patients along with a decrease in the
      side effects, thus suggesting the need to change the infusion intervals in
      suitable patients.

PMID- 30206669
TI  - A3 adenosine receptor agonist attenuates neuropathic pain by suppressing
      activation of microglia and convergence of nociceptive inputs in the spinal
      dorsal horn.
AB  - Peripheral nerve injuries cause glial activation and neuronal hyperactivity in
      the spinal dorsal horn. These changes have been considered to be involved in the
      underlying mechanisms for the development and maintenance of neuropathic pain.
      Using double immunofluorescence labeling, we previously demonstrated that spinal
      microglial activation induced by nerve injury enhanced convergence of nociceptive
      inputs in the spinal dorsal horn from uninjured afferents. The adenosine A3
      receptor (A3AR) agonists have been shown to have antinociceptive activities in
      several experimental neuropathic pain models. However, the mechanisms underlying
      these antinociceptive actions of the A3AR agonist are still not fully explored.
      In this study, the effects of the A3AR agonist (i.e., IB-MECA) on microglial
      activation, enhancement of convergent nociceptive inputs, and nocifensive
      behaviors were examined after tibial nerve injury. Injury to the tibial nerve
      initially caused hyposensitivity to touch stimulus at 3 days, and then resulted
      in tactile allodynia at 14-day post-injury. The daily systemic administration of
      IB-MECA (0.1 mg/kg/day) for 8 days in a row starting on the day of nerve injury
      or 7 days after nerve injury prevented the development of behaviorally assessed
      hypersensitivities, and spinal microglial activation induced by nerve injury.
      These treatments also suppressed anomalous convergence of nociceptive primary
      inputs in the spinal dorsal horn. The present findings indicate that the A3AR
      agonist attenuates neuropathic pain states by suppressing enhanced microglial
      activation, and anomalous convergence of nociceptive inputs in the spinal dorsal
      horn from uninjured afferents after injury to the peripheral nerve.

PMID- 30206672
TI  - High burden of skin sclerosis is associated with severe organ involvement in
      patients with systemic sclerosis and systemic sclerosis overlap syndrome.
AB  - The objective of this study is to investigate the impact of skin sclerosis burden
      on an internal organ involvement over a 1-year period, as measured by time
      adjusted accrual-modified Rodnan skin score (TA-mRSS), and to evaluate
      association between TA-mRSS patterns and laboratory tests in patients with
      systemic sclerosis (SSc). This prospective study was conducted at Siriraj
      Hospital (Bangkok, Thailand) during the November 2013-November 2016. SSc patients
      by ACR/EULAR 2013 or ACR 1980 criteria were eligible. TA-mRSS was classified as
      low, intermediate, or high, and then compared between groups. Correlation between
      the arithmetic mean of laboratory tests and TA-mRSS was assessed by multiple
      linear regression analysis. A total of 118 patients, with 81.4% women, median
      (IQR) age 49.8 (43.8, 55.1) years, disease duration from onset of non-Raynaud
      symptoms to first visit of 3.3 (1, 6.8) years, 78% dcSSc, and 75.3% anti-Scl-70
      positivity, were analyzed. TA-mRSS over 1 year ranged from 0 to 37.44. The high
      skin sclerosis burden group had a median TA-mRSS > 7.26 (> 67th percentile).
      Patients with high TA-mRSS were dcSSc, high initial and average mRSS, and had
      tendon friction rub, digital ischemic complications, usual interstitial
      pneumonia, diastolic dysfunction, gastrointestinal dysmotility, and low serum
      albumin. In multiple linear regression analysis, the arithmetic mean of
      hemoglobin (B = - 1.007, 95% CI - 1.779 to - 0.236), erythrocyte sedimentation
      rate (B = - 0.078, 95% CI - 0.126 to - 0.029), serum glutamic oxaloacetic
      transaminase (B = 0.073, 95% CI 0.026-0.12), creatine phosphokinase (B = 0.012,
      95% CI 0.003-0.021), and albumin (B = - 4.117, 95% CI - 6.958 to - 1.276) were
      associated with TA-mRSS. This study found a higher cumulative course of mRSS over
      a 1-year period to be significantly associated with severe internal organ
      involvement.

PMID- 30206675
TI  - Magnetic resonance imaging of the craniovertebral junction in early rheumatoid
      arthritis.
AB  - OBJECTIVE: To assess the involvement of the atlantoaxial joint in patients with
      early rheumatoid arthritis (ERA) and to elucidate the risk profile for the
      individual patient. MATERIALS AND METHODS: Consecutive ERA patients (disease
      duration < 12 months) were included in our study. A cervical spine magnetic
      resonance imaging (MRI) and X-rays (cervical spine, hands, wrists, and feet) were
      performed in all patients. The MRI features were correlated with clinical,
      radiological, and biochemical variables. RESULTS: Fifty patients (13 men and 37
      women) with a mean age of 58.2 years (range, 36-79 years) were included in the
      study. In 12 (24%) patients were detectable MRI findings suggestive of the
      craniovertebral junction involvement. Compared with patients without cervical
      involvement, the patients with atlantoaxial synovitis showed a significantly
      higher anti-citrullinated protein antibodies (ACPA) titer [mean 200.25 UI (SD
      262.44) vs. mean 22.05 (SD 40.21) (p < 0.001)]; a worse Disease Activity Score 44
      joints (DAS44) [mean 5.72 (SD 0.44) vs. mean 4.52 (SD 0.53) (p < 0.001)]; a worse
      Health Assessment Questionnaire Disability Index (HAQ-DI) [mean 1.55 (SD 0.37)
      vs. mean 1.09 (SD 0.33) (p < 0.001)], and a higher Simple Erosion Narrowing Score
      (SENS) [mean 15.83 (SD 4.52) vs. mean 7.71 (SD 3.43) (p < 0.001)]. The
      multivariate analysis revealed a meaningful relationship between atlantoaxial
      synovitis and ACPA, DAS44, and the presence of an erosive disease. CONCLUSIONS:
      The craniovertebral junction is frequently involved in ERA patients. ACPA, high
      disease activity, and erosive disease at baseline are predictors of atlantoaxial
      involvement.

PMID- 30206671
TI  - Sleep impairment: an obstacle to achieve optimal quality of life in rheumatoid
      arthritis.
AB  - Sleep impairment is a common clinical condition in patients with rheumatoid
      arthritis. There are several confounding factors for poor sleep quality including
      inflammation, pain, comorbidities, and medications. Consequences of impaired
      sleep vary within a wide spectrum, as well. These include exacerbated
      inflammation and inflammation-related symptoms, mental and physical fatigue, mood
      disorders, daytime sleepiness, and poor quality of life. Sleep impairment in
      rheumatoid arthritis and its association with disease-related variables including
      health-related quality of life have been studied several times in the literature.
      Therefore, it would be of value to review the existing data on the crosstalk
      between sleep and rheumatoid arthritis. In the present article, the mechanism,
      confounders, and consequences of this association will be reviewed in detail. The
      evaluation of sleep impairment in rheumatoid arthritis along with the potential
      management strategies will be discussed.

PMID- 30206676
TI  - Intra-articular fibroma-like perivascular epithelioid tumor (PEComa) mimicking
      tenosynovial giant cell tumor, diffuse type.
AB  - Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal neoplasms
      composed of perivascular epithelioid cells that are immunoreactive for both
      melanocytic and myogenic markers. Recently, a fibroma-like PEComa associated with
      tuberous sclerosis complex (TSC) has been identified. We describe the first intra
      articular case of a fibroma-like PEComa in a 44-year-old man who presented with a
      hypointense intra-articular knee mass, which was mistaken for tenosynovial giant
      cell tumor, diffuse type. This case report demonstrates that fibroma-like PEComa
      should be included in the extended differential diagnosis of intra-articular soft
      tissue masses. In addition, given their strong association with TSC mutations, a
      diagnosis of fibroma-like PEComa should trigger an evaluation for TSC.

PMID- 30206674
TI  - Percutaneous ozone nucleolysis for lumbar disc herniation.
AB  - PURPOSE: All percutaneous minimally invasive disc treatments are typically
      indicated to contained disc herniations. Our study's aim is to evaluate
      prospectively the efficacy of ozone nucleolysis in the treatment of either
      contained or uncontained lumbar disc herniations. METHODS: Fifty-two patients,
      aged 27-87 years, with symptomatic herniated lumbar discs, without migration,
      sequestration, or severe degenerative disc changes, who failed conservative
      treatment, were included in our study. The patients underwent fluoroscopic-guided
      intradiscal oxygen-ozone mixture injection (5 ml) at a concentration of 27-30
      MUg/ml and periradicular injection of the same O2-O3 mixture (10 ml), steroid (1
      ml), and local anesthetic (1 ml). Clinical outcomes were evaluated, based on the
      Oswestry Disability Index (ODI) and pain intensity (0-5) scale results, obtained
      initially and at 2- and 6-month controls. Our results were analyzed by ANOVA and
      chi-squared (chi2) tests. RESULTS: Our initial results obtained at 2-month
      control were promising, indicating a significant decrease in pain disability and
      intensity in 74% (37) and 76% (38) of the patients respectively, and minimally
      increased to 76% (38) and 78% (39) at 6-month control (P < 0.001 and CI 99.9%).
      The mean preprocedure ODI and pain intensity scores were 35 +/- 14.36 and 2.38 +/
      0.90, respectively, which were reduced to 19.36 +/- 13.12 and 1.04 +/- 0.92 at 6
      month control. Our failure had been mostly related to long symptoms duration of
      more than 1 year. No complications were recorded. CONCLUSION: Ozone nucleolysis
      is a safe cost-effective minimally invasive technique for treatment of contained
      and uncontained lumbar disc herniations.

PMID- 30206673
TI  - Changes in the regional shape and volume of subcortical nuclei in patients with
      tinnitus comorbid with mild hearing loss.
AB  - PURPOSE: Tinnitus, the perception of sound without an external source, is a
      prevalent disease, but its underlying mechanism has not been fully elucidated.
      Recent studies have suggested the involvement of subcortical nuclei in tinnitus
      generation. We investigated changes in the local shape and volume of subcortical
      nuclei in relation to tinnitus. METHODS: The participants included 53 patients
      with tinnitus and 52 age- and gender-matched normal controls. Individual 3D T1
      weighted structural images were obtained using 3-T magnetic resonance imaging.
      Surface-based vertex analysis (SVA) was performed with automated segmentation of
      the bilateral caudate nuclei, putamina, nucleus accumbens, thalami, pallidum,
      hippocampi, amygdalae, and brainstem. The scalar distances from the mean surface
      and volumes of 15 nuclei were compared between the tinnitus and control groups
      and correlated with tinnitus handicap score (THI) and tinnitus duration. RESULTS:
      SVA revealed regional contractions in the accessory basal and lateral nuclei of
      the right amygdala and expansions in the left medial and right ventral posterior
      nuclei and lateral dorsal nucleus of both thalami. The surface distances of the
      right nucleus accumbens were positively correlated with tinnitus duration, while
      those of the left nucleus accumbens and left hippocampus were negatively
      correlated with THI. CONCLUSION: Regional atrophy of the amygdala may indicate
      self-modulation of emotional response regulation to diminish tinnitus-related
      emotional distress. Thalamic regional expansion may signify dysfunctional
      auditory gating in the thalamus, where inhibition of the tinnitus signal at the
      thalamus level is disrupted due to abnormal changes in the limbic system,
      ultimately leading to the tinnitus percept.

PMID- 30206677
TI  - Ultrasound-guided injection for the diagnosis and treatment of posteromedial knee
      friction syndrome.
AB  - OBJECTIVE: To describe an ultrasound guided injection technique for diagnosing
      and treating posteromedial knee friction syndrome, which occurs between the
      sartorius/gracilis tendons and medial femoral condyle (MFC). MATERIALS AND
      METHODS: Our study was IRB-approved and HIPAA-compliant. We identified patients
      via a retrospective review of medical records and MRI with posteromedial knee
      pain and isolated edema between MFC and sartorius/gracilis tendons and no
      evidence for meniscal tear, ruptured Baker's cyst or degenerative joint disease.
      Patients were referred for an ultrasound-guided procedure to inject anesthetic
      and corticosteroid at the site of edema. Procedures were evaluated for technical
      success, which was defined as satisfactory identification of the injection site
      and adequate delivery of medication. Follow-up was available up to 8 weeks after
      the procedure to determine the response and any potential complications. RESULTS:
      Fourteen subjects with MRI and symptoms of posteromedial knee friction syndrome
      underwent 14 injections. Technical success was achieved in all procedures, with
      no complications. At 8 weeks' follow-up, 92% of patients had symptom improvement.
      VAS before and 8 weeks after the procedure changed from 5.2 +/- 2.7 to 0.9 +/-
      2.1 (p = 0.0002), respectively. CONCLUSION: Ultrasound-guided injection of edema
      between the MFC and sartorius/gracilis tendons supports the diagnosis of a
      posteromedial knee friction syndrome and successfully treats its associated
      symptoms.

PMID- 30206679
TI  - Peripheral nerve injuries in the pediatric population: a review of the
      literature. Part III: peripheral nerve tumors in children.
AB  - INTRODUCTION: Peripheral nerve tumors type, inciedence and treatment in the
      pediatric population should be analyzed. METHODS: We have performed an extense
      literature review of this subject. RESULTS: incidence and distribution are
      similar to those observed in adults. The most common peripheral nerve tumors in
      children are neurofibromas and schwannomas. Malignant peripheral nerve sheath
      tumors are also observed, specially associated with genetic syndromes, like
      neurofibromatosis and Carney complex. CONCLUSION: In this review, peripheral
      nerve tumors have been divided into three categories to aid with understanding:
      reactive and hyperplastic lesions, benign tumors, and malignant tumors. The most
      frequent lesions have been described.

PMID- 30206678
TI  - Anterior capsular abnormality: another important MRI finding for the diagnosis of
      adhesive capsulitis of the shoulder.
AB  - OBJECTIVE: To evaluate the usefulness of anterior capsular abnormality,
      thickening, and abnormal signal intensity on MRI for the diagnosis of adhesive
      capsulitis of the shoulder. MATERIALS AND METHODS: This retrospective study
      included 29 patients with adhesive capsulitis and 20 controls. Clinical criteria
      with significant restricted passive motion was used for the diagnosis of adhesive
      capsulitis. The anterior capsular thickness and signal intensity were evaluated
      on the thickest portion of anterior glenohumeral joint capsule, located deep to
      the subscapularis muscle. In addition, the previously known MR findings of
      adhesive capsulitis, such as humeral and glenoid capsular thickness in axillary
      recess, maximal axillary capsular thickness, and coracohumeral ligament
      thickness, were measured. The presence of humeral and glenoid capsular abnormal
      hyperintensity in axillary recess, abnormal hyperintensity, and obliteration of
      the subcoracoid fat triangle were also evaluated. RESULTS: All MRI findings
      significantly differed between adhesive capsulitis and controls. Among MR
      findings, multivariable analysis showed that anterior capsular thickness, maximal
      axillary capsular thickness, and anterior capsular abnormal hyperintensity were
      variables that could differentiate adhesive capsulitis from the control group,
      with odds ratios of 7.97, 17.75, and 12.41, respectively (p < 0.05). In ROC
      analysis, the anterior capsular thickness showed high diagnostic performances
      with an AUC of 0.897. The cut-off value of anterior capsular thickness at 3.5 mm
      showed excellent diagnostic accuracy, with sensitivity of 68.97% and specificity
      of 100%. CONCLUSIONS: Anterior capsular abnormality, thickening, and abnormal
      hyperintensity can be used for the diagnosis of adhesive capsulitis of shoulder,
      in addition to previously known abnormal MRI findings.

PMID- 30206681
TI  - A systematic literature review on solitary rectal ulcer syndrome: is there a
      therapeutic consensus in 2018?
AB  - PURPOSE: To screen all treatments tested for solitary rectal ulcer syndrome
      (SRUS) without rectal prolapse and to assess their efficacy. METHOD: A systematic
      review was performed according to the PRISMA guidelines, focusing on the
      treatment of SRUS without rectal prolapse. The types of treatment and their
      efficacy were collected and critically assessed. RESULTS: A selection of 20
      studies among the 470 publications focusing on SRUS provided suitable data for a
      total of 516 patients. Only 2 studies were randomised prospective trials that
      focused on argon plasma treatment. The mean follow-up was 21.8 months and ranged
      from 0.25 to 90 months. Most of the studies focused on surgery, including
      rectopexy, stapled transanal rectal resection, excision of the ulcer, the Delorme
      procedure, proctectomy, low anterior resection, and ostomy. Populations of the
      studies were heterogeneous and selected outcomes were specific (failure of
      medical or surgical treatment). Conservative treatment (high-fibre diet,
      laxatives, change of defecatory habits, and biofeedback treatment) induced a
      symptomatic improvement in 71/91 patients (63.6%) and healing of mucosal lesion
      in 17/51 patients (33.3%). Surgeries (all types) improved SRUS in 77% (54-100%)
      of patients. Argon plasma coagulation is a promising technique but longer follow
      up is necessary. CONCLUSIONS: The general quality of the studies focusing on the
      treatment of SRUS was poor due to the heterogeneity of the population, the sample
      size of the cohorts, and the heterogeneity of efficacy assessments. The
      therapeutic approach appears to be multimodal and multidisciplinary and validated
      in centres of expertise. Further studies evaluating multimodal strategies are
      needed.

PMID- 30206680
TI  - Vestibular-related eye movements in the rat following selective electrical
      stimulation of the vestibular sensors.
AB  - Rats are the most commonly used species in the neurosciences; however, little is
      known about the effects of selective electrical stimulation of individual
      vestibular sensors, on their eye movements. This limits their use to study the
      effects of vestibular stimulation on the brain, and their use in further
      exploring novel technologies such as artificial vestibular implants. We describe
      the effects of electrical stimulation of each vestibular sensor on vestibular
      related eye movement in rats and compared the results to other species. We
      demonstrated that each sensor is responsible for specific bilateral eye
      movements. We found that the eye movements in rats differed from other species.
      Although the results were similar when stimulating the horizontal canal ampulla,
      differences appeared when stimulating the vertical canal sensors. During
      utricular stimulation, the ipsilateral eye moved dorsally in most cases, while
      the contralateral eye usually moved either caudally, or in extorsion. Saccular
      stimulation usually moved the ipsilateral eye dorsally or ventrally, while the
      contralateral eye usually moved ventrally or caudally. This study provides the
      first data on the application of selective electrical vestibular stimulation in
      the rat to the study of vestibular-related eye movements.

PMID- 30206682
TI  - [Rheumatism operations in a state of flux-"Foot"].
AB  - Surgical management of rheumatic feet has dramatically changed over the last
      decades influenced by the development of new pharmacological drugs and tissue
      preserving surgical procedures. It has switched from joint resection to joint
      sparing procedures as the method of choice. Nevertheless, the surgical
      interventions commonly used for non-rheumatic patients cannot be applied to
      rheumatic patients without reflection: in addition to the basic treatment,
      comorbidities, degree of mobilization of the patient, orthopedic shoe engineering
      and orthotic treatment play a major role. Due to the decreasing incidence of the
      classical rheumatic foot, it has become even more important for physicians,
      physiotherapists and ergotherapists to recognize the development of such a
      disease as early as possible and immediately start the appropriate treatment.

PMID- 30206683
TI  - Malignant colorectal polyps: endoscopic polypectomy and watchful waiting is not
      inferior to subsequent bowel resection. A nationwide propensity score-based
      analysis.
AB  - BACKGROUND AND AIMS: The optimal treatment of patients with malignant colorectal
      polyps is unsettled. The surgical dilemma following polypectomy is selecting
      between watchful waiting (WW) and subsequent bowel resection (SBR), but the long
      term survival outcomes have not been established yet. This nationwide study
      compared survival of patients after WW or SBR. METHODS: Danish nationwide study
      with 100% follow-up of all patients with malignant colorectal polyps (the Danish
      Colorectal Cancer Group database) in a 10-year period from 2001 to 2011. All
      patients' charts and histological reports were individually reviewed. Survival
      rates were calculated with Cox proportional hazard model after propensity score
      matching. RESULTS: A total of 692 patients were included (WW, 424 (61.3%), SBR,
      268 (38.7%)) with a mean follow-up of 7.5 years (3-188 months). Following
      propensity score matching, there was no significant difference in overall or
      disease-free survival (p = 0.344 and p = 0.184) or rate of local recurrence (WW,
      7.2%, SBR, 2%, p = 0.052) or distant metastases (WW, 3.3%, SBR, 4.6%, p = 0.77).
      In the SBR group, there was no residual tumor or lymph node metastases in the
      resected specimen in 82.5% of the patients. CONCLUSION: Subsequent bowel
      resection may not be superior to endoscopic polypectomy and watchful waiting with
      regard to overall and disease-free survival in patients with malignant colorectal
      polyps.

PMID- 30206685
TI  - Attention for future reward.
AB  - When stimuli are consistently paired with reward, attention toward these stimuli
      becomes biased (e.g., Abrahamse, Braem, Notebaert & Verguts, et al.,
      Psychological Bulletin 142:693-728, 2016, https://doi.org/10.1037/bul0000047 ).
      An important premise is that participants need to repeatedly experience stimulus
      reward pairings to obtain these effects (e.g., Awh, Belopolsky & Theeuwes, Trends
      in Cognitive Sciences 16:437-443, 2012,
      https://doi.org/10.1016/j.tics.2012.06.010 ). This idea is based on associative
      learning theories (e.g., Pearce & Bouton, Annual Review of Psychology 52:111-139,
      2001) that suggest that exposure to stimulus-reward pairings leads to the
      formation of stimulus-reward associations, and a transfer of salience of the
      reward to the neutral stimulus. However, novel learning theories (e.g., De
      Houwer, Learning and Motivation 53:7-23, 2009,
      https://doi.org/10.1016/j.lmot.2015.11.001 ) suggest such effects are not
      necessarily the result of associative learning, but can be caused by complex
      knowledge and expectancies as well. In the current experiment, we first
      instructed participants that a correct response to one centrally presented
      stimulus would be followed by a high reward, whereas a correct response to
      another centrally presented stimulus would be paired with a low reward. Before
      participants executed this task, they performed a visual probe task in which
      these stimuli were presented as distractors. We found that attention was drawn
      automatically toward high-reward stimuli relative to low-reward stimuli. This
      implies that complex inferences and expectancies can cause automatic attentional
      bias, challenging associative learning models of attentional control (Abrahamse
      et al., 2016; Awh et al., 2012).

PMID- 30206684
TI  - Comparison of six display modes for a multi-resolution foveated laparoscope.
AB  - BACKGROUND: To overcome the field of view and ergonomic limitations of standard
      laparoscopes, we are developing a multi-resolution foveated laparoscope that can
      simultaneously obtain both wide- and zoomed-in-view images through a single
      scope. To facilitate the effective access to the dual views of images with
      different resolution and field coverage acquired by our laparoscope, six
      different display modes have been developed. Each of the six display modes has
      inherent advantages and disadvantages. This study compares the six display modes
      through a human-subject experiment, which was conducted with an emulated
      laparoscope using a 4K camera. METHODS: Twenty-four subjects without medicine
      background performed three evaluation trials of a touching task with each of the
      display modes. Various objective measurements including task completion time, the
      number of collisions, gaze position, and tooltip position, and subjective
      preference for the display modes were recorded. RESULTS: For all the measurements
      except for task completion time and moving speed of tooltip, there were
      statistically significant differences among the display modes. Although the focus
      plus warped context view mode was selected as one of the least preferred modes,
      it showed the best task performance. CONCLUSIONS: The unblocked wide context view
      was useful to provide a situational awareness even when it was severely distorted
      in some of the display modes, and information continuity played an important role
      in improving task performance. Moreover, the position change of viewing window
      coupled to the location of region of interest helped improve task performance, by
      providing an additional cue for spatial awareness.

PMID- 30206686
TI  - De novo brain arteriovenous malformation after tumor resection: case report and
      literature review.
AB  - The congenital origin of brain arteriovenous malformations (bAVMs) has been
      increasingly challenged by reports of de novo bAVMs in patients previously
      confirmed to have no vascular malformation. We describe the oldest patient
      reported in the English language literature harboring a de novo bAVM. An
      uneventful frontal convexity meningioma resection was performed for a 60-year-old
      woman, and at 67 years of age, a bAVM was detected by MRI and confirmed by
      digital subtraction angiography at the site of the previous meningioma resection.
      This case adds to the growing literature that the etiology of bAVMs is most
      likely multifactorial.

PMID- 30206687
TI  - Oxidative stress induced in chloroplasts or mitochondria promotes proline
      accumulation in leaves of pea (Pisum sativum): another example of chloroplast
      mitochondria interactions.
AB  - Oxidative stress can occur in different parts of plant cells. We employed two
      oxidants that induce reactive oxygen species (ROS) in different intracellular
      compartments: methyl viologen (MV, in chloroplasts) and menadione (MD, in
      mitochondria). The responses of pea (Pisum sativum) leaf discs to MV or MD after
      4-h incubation in dark or moderate (300 MUE m-2 s-1) or high light (1200 MUE m-2
      s-1) were examined. Marked increase in ROS levels was observed, irrespective of
      compartment targeted. The levels of proline, a compatible solute, increased
      markedly much more than that of ascorbate or glutathione during oxidative/photo
      oxidative stress, emphasizing the importance of proline. Further, the activities
      and transcripts of enzymes involved in biosynthesis or oxidation of proline were
      studied. An upregulation of biosynthesis and downregulation of oxidation was the
      basis of proline accumulation. Pyrroline-5-carboxylate synthetase (P5CS, involved
      in biosynthesis) and proline dehydrogenase (PDH, involved in oxidation) were the
      key enzymes regulated under oxidative stress. Since these two enzymes-P5CS and
      PDH-are located in chloroplasts and mitochondria, respectively, we suggest that
      proline metabolism can help to mediate inter-organelle interactions and achieve
      redox homeostasis under photo-oxidative stress.

PMID- 30206691
TI  - Accuracy of the Demirjian and Willems methods of dental age estimation for
      children from central southern China.
AB  - The aim of this study was to compare the accuracy of the Demirjian method and the
      Demirjian method as revised by Willems for age estimation based on
      orthopantomograms from central southern Chinese Han population aged 8-16 years.
      Discrepancies between chronological and estimated ages were statistically
      evaluated by analyzing 1249 orthopantomograms from 603 girls and 646 boys. Using
      the Demirjian method, the mean age estimates underestimated chronological age by
      0.03 years (p = 0.48) for girls and overestimated it by 0.03 years (p = 0.59) for
      boys; these differences with respect to chronological age were not statistically
      significant. In contrast, the Willems method underestimated chronological age by
      0.54 years (p < 0.01) for girls and 0.44 years (p < 0.01) for boys; these
      differences with respect to chronological age were statistically significant.
      Compared to the Demirjian method, the overall mean absolute error generated using
      the Willems method was slightly higher (0.85 and 0.86 years, respectively). Since
      the Demirjian method was more accurate, we highly recommend that it should be
      applied when estimating dental age in the Chinese Han population. Further
      modifications of these two methods for populations from other regions and
      additional studies of other age groups are warranted.

PMID- 30206689
TI  - A dipteran larva-pitcher plant digestive mutualism is dependent on prey resource
      digestibility.
AB  - Positive species interactions tend to be context dependent. However, it is
      difficult to predict how benefit in a mutualism changes in response to changing
      contexts. Nepenthes pitcher plants trap animal prey using leaf pitfall traps
      known as pitchers. Many specialized inquiline organisms inhibit these pitchers,
      and are known to facilitate the digestion of prey carcasses in them. Nepenthes
      gracilis traps diverse arthropod prey taxa, which are likely to differ greatly in
      the ease with which they may be digested, independently of inquilines, by plant
      enzymes. In this study, we used in vitro experiments to compare the nutritional
      benefit provided by phorid (scuttle fly) and culicid (mosquito) dipteran larvae
      to their host, N. gracilis, and to each other. The effects of phorids on N.
      gracilis nutrient sequestration were very variable, being positive for large prey
      which have low digestibility, but negative for small prey which are highly
      digestible. However, the effect of culicids on N. gracilis and the effects of
      culicids and phorids on each other were not significantly altered by prey type.
      These results show that a digestive mutualism is highly dependent on the
      digestibility of the resource-a context dependency that conforms well to the
      predictions of the stress-gradient hypothesis in facilitation research. Our
      findings have significant implications for many other digestive mutualisms, and
      also suggest that greater insights may be gained from the synthesis of concepts
      between the fields of mutualism and facilitation research.

PMID- 30206688
TI  - Chronic dryness and wetness and especially pulsed drought threaten a generalist
      arthropod herbivore.
AB  - Under climate change, both wetter and drier conditions, as well as an increase in
      extreme events like floods or droughts are projected for many areas. So far,
      studies only investigate the impact of drier or wetter conditions at a single
      stress severity level but do not consider how different intensities and types of
      changes affect insect herbivores feeding on stressed plants. Further, how effects
      of acute stress pulses differ from milder, chronic soil moisture stress is
      unclear. We investigated how changing soil moisture conditions affect a
      generalist insect herbivore feeding on grassland plants. We transplanted multi
      species sections of grassland into pots and subjected them to different
      intensities and durations of flooding and drying stress. We compared effects of
      short, extreme drought and flooding pulses against the effects of milder, but
      chronic stress. Constantly drier conditions decreased plant and herbivore
      performance at all levels of stress severity. Severe permanent wetness did not
      affect plant growth, but decreased pupal weight (- 23%) and survival of larvae (-
      34%). Extreme pulsed drought exacerbated negative effects of chronic drying, as
      most larvae died before they could benefit from rewetting plants after the
      drought (94% mortality). Pulsed flooding did not affect plants or larval
      development more than chronic severe wetness. Our findings imply that plant
      stress negatively affects generalist chewing herbivores, even with mixed diets.
      Both drier and severely wet, but not mildly wetter conditions, will reduce
      survival of some species. Especially, extreme droughts appear to have strong
      negative effects on generalist grassland herbivores.

PMID- 30206690
TI  - Effect of remifentanil on postoperative nausea and vomiting: a randomized pilot
      study.
AB  - Opioid-related postoperative nausea and vomiting should not occur following
      remifentanil administration because of its relatively short time to elimination.
      However, studies have indicated that the incidence of postoperative nausea and
      vomiting associated with remifentanil is similar to that with other opioids.
      Hence, we aimed to determine whether intraoperative remifentanil itself is
      associated with postoperative nausea and vomiting when postoperative pain is
      managed without opioid use. In this prospective pilot study, 150 patients who
      underwent unilateral upper limb surgery under general anesthesia with brachial
      plexus block were included. Patients in the remifentanil and control groups
      received 0.5 ug/kg/min remifentanil and saline, respectively. Postoperative pain
      was managed using a brachial plexus block, non-steroidal anti-inflammatory drugs,
      and acetaminophen. The presence of postoperative nausea and vomiting within the
      first 24 h after anesthesia was assessed by an evaluator blinded to patient
      allocation. Eight patients were excluded from the final analysis, resulting in 72
      and 70 patients in the remifentanil and control groups, respectively.
      Postoperative nausea and vomiting within 24 h after surgery occurred in 11 and 9
      patients in the remifentanil and control groups, respectively. These data suggest
      that remifentanil use only minimally affects the incidence of postoperative
      nausea and vomiting under sevoflurane anesthesia. UMIN Clinical Trials Registry
      identification number: UMIN000016110.

PMID- 30206693
TI  - Surgical increase in thoracic kyphosis increases unfused lumbar lordosis in
      selective fusion for thoracic adolescent idiopathic scoliosis.
AB  - PURPOSE: In adolescent idiopathic scoliosis (AIS), there is a close relationship
      between thoracic kyphosis (TK) and proximal lumbar lordosis (PLL). The hypothesis
      states correction of hypokyphosis increases lumbar lordosis (LL) through increase
      in PLL after surgical correction of TK. METHODS: 111 consecutive thoracic AIS,
      Lenke 1 or 2 who underwent posterior selective thoracic fusion with reduction by
      simultaneous translation on 2 rods and 2 years follow-up have been prospectively
      selected and analyzed. Instrumentations below L1 and anterior releases were
      excluded. Global TK and LL were measured by a dedicated software. Mean values
      were compared through T test, correlations assessed through Pearson's
      coefficient. RESULTS: Global TK increased from 27 degrees  to 46 degrees  at the
      last follow-up (p < 0.0001) and LL from 58 degrees  to 65 degrees  (p < 0.0001).
      PLL increased by 8 degrees  (15 degrees -23 degrees ), and distal lumbar lordosis
      remained stable (42 degrees ). The gains were higher for the Hypo-Kyphosis group
      than for the Normo-Kyphosis group (p < 0.001). There was a strong correlation
      (coef = 0.65) between TK and PLL as well as between the gain of TK and the gain
      of PLL (coef = 0.70). LL increased after the first postoperative month. At 1
      month, there was a significant increase in pelvic tilt and decrease in sacral
      slope, offsetting the LL increase, and indicating a temporary pelvic
      retroversion. CONCLUSIONS: Increase in TK led to increase in uninstrumented LL
      through increase in PLL with a continuous correlation between TK and PLL. These
      results allow surgeons to calculate the TK required during surgical correction of
      thoracic AIS to adapt LL to pelvic incidence. These slides can be retrieved under
      Electronic Supplementary Material.

PMID- 30206696
TI  - beta-(1,4)-Galactan remodelling in Arabidopsis cell walls affects the xyloglucan
      structure during elongation.
AB  - MAIN CONCLUSION: Galactan turnover occurs during cell elongation and affects the
      cell wall xyloglucan structure which is involved in the interaction between
      cellulose and xyloglucan. beta-(1,4)-Galactan is one of the main side chains of
      rhamnogalacturonan I. Although the specific function of this polymer has not been
      completely established, it has been related to different developmental processes.
      To study beta-(1,4)-galactan function, we have generated transgenic Arabidopsis
      plants overproducing chickpea betaI-Gal beta-galactosidase under the 35S CaMV
      promoter (35S::betaI-Gal) to reduce galactan side chains in muro. Likewise, an
      Arabidopsis double loss-of-function mutant for BGAL1 and BGAL3 Arabidopsis beta
      galactosidases (bgal1/bgal3) has been obtained to increase galactan levels. The
      characterization of these plants has confirmed the role of beta-(1,4)-galactan in
      cell growth, and demonstrated that the turnover of this pectic side chain occurs
      during cell elongation, at least in Arabidopsis etiolated hypocotyls and floral
      stem internodes. The results indicate that BGAL1 and BGAL3 beta-galactosidases
      act in a coordinate way during cell elongation. In addition, this work indicates
      that galactan plays a role in the maintenance of the cell wall architecture
      during this process. Our results point to an involvement of the beta-(1,4)
      galactan in the xyloglucan structure and the interaction between cellulose and
      xyloglucan.

PMID- 30206698
TI  - Correction to: Use of flash glucose-sensing technology (FreeStyle Libre) in youth
      with type 1 diabetes: AWeSoMe study group real-life observational experience.
AB  - Unfortunately, the co-author name was misspelled as "Avivit Brenner" instead of
      "Avivit Brener" in the original publication and the correct author name is
      updated here.

PMID- 30206694
TI  - Visualization of internal in situ cell structure by atomic force microscopy.
AB  - Light and electron microscopy have been used to study cell structure for many
      years, but atomic force microscopy is a more recent technique used to analyze
      cells, mainly due to the absence of techniques to prepare the samples. Isolated
      molecules or organelles, whole cells, and to a lesser extent in situ cell
      structure have been observed by different atomic force microscopy imaging modes.
      Here, we review efforts intended to analyze in situ the cell structures using
      approaches involving imaging of the surface of semithin sections of samples
      embedded in resin and sections prepared with an ultramicrotome. The results of
      such studies are discussed in relation to their implications to analyze the fine
      structure of organelles at the nanoscale in situ at enhanced resolution compared
      to light microscopy.

PMID- 30206692
TI  - Physiological resolution of periodic breath holding during heavy-intensity
      Fartlek exercise.
AB  - PURPOSE: The purpose was to compare the singular and combined effects of 5 s
      breath holds (BH) and 5 s sprints, every 30 s, during continuous high-intensity
      exercise, on ventilation ([Formula: see text]), oxygen uptake ([Formula: see
      text]O2) and associated kinetics (tau), carbon dioxide production ([Formula: see
      text]CO2), and arterialized-capillary lactate concentration ([La-]). METHODS: Ten
      men (24 +/- 3 years) performed 4-6 min ergometer protocols that included a step
      transition from 20 W to a power output of 50% of the difference between lactate
      threshold and [Formula: see text]O2 peak (Delta50%) including: (1) a continuous
      protocol (CONT) with free breathing, (2) an intermittent BH protocol (CONT-BH);
      repeated cycles of 5 s BH: 25 s free breathing, (3) a Fartlek protocol (Fartlek);
      repeated 5 s at peak aerobic power output: 25 s at Delta50%; (4) combining the 5
      s Fartlek and CONT-BH protocol (Fartlek-BH). Breath-by-breath gas exchange,
      measured by mass spectrometry and turbine, was recorded. RESULTS: [Formula: see
      text] E (L min-1) was greater (p < 0.05) than CONT (90 +/- 7) in all conditions
      CONT-BH (98 +/- 16), Fartlek (105 +/- 10), and Fartlek-BH (101 +/- 19). [Formula:
      see text]O2 and [Formula: see text]CO2 (L min-1) were unchanged in CONT-BH (2.73
      +/- 0.14 and 3.16 +/- 0.38) and greater in Fartlek (2.85 +/- 0.12 and 3.43 +/-
      0.16), compared to CONT (2.71 +/- 0.12 and 3.12 +/- 0.13). Whereas, [Formula: see
      text]CO2 during Fartlek-BH was higher (3.28 +/- 0.35) and [Formula: see text]O2
      was unchanged (2.73 +/- 0.14). Fartlek-BH resulted in slower [Formula: see
      text]O2 kinetics (62.2 +/- 19 s) and greater blood lactate concentrations (11.5
      +/- 2.7 mM), compared to CONT (48.8 +/- 12 s; 9.0 +/- 2.3 mM, respectively).
      CONCLUSIONS: It was demonstrated that the CONT-BH resulted in increased
      ventilation that sustained [Formula: see text]O2. However, [Formula: see text]O2
      was restricted when an additional work was combined with the BH condition.

PMID- 30206695
TI  - Comparison of measured and calculated doses in a Rando phantom with a realistic
      lung radiotherapy treatment plan including heterogeneities.
AB  - In this work, dose measurements were performed to evaluate an external
      radiotherapy treatment plan and, particularly, to validate dose calculations for
      a lung lesion case. Doses were calculated by the Varian Eclipse treatment
      planning system using the AAA anisotropic analytical algorithm. The measurements
      were performed using a Rando anthropomorphic phantom and TLD700 thermoluminescent
      dosimeters. The comparison between doses calculated and doses measured by means
      of thermoluminescence (TL) shows compatibility except for a few points, due to
      the limitations in the heterogeneity correction used for the case studied here.
      The deviation between the calculated and measured doses is about 6.5% for low (<
      0.5 Gy) doses and about 1% for higher doses (> 0.5 Gy).The deviation between AAA
      calculated and TL-measured doses was also found to be higher in proximity to
      heterogeneous tissue interfaces.

PMID- 30206699
TI  - Issue focusing: a new topical collection on diabetic nephropathy.

PMID- 30206697
TI  - Dexmedetomidine restores autophagy and cardiac dysfunction in rats with
      streptozotocin-induced diabetes mellitus.
AB  - AIMS: Dexmedetomidine (DEX), a highly selective and potent alpha2-adrenergic
      receptor agonist, has anti-apoptotic, anti-inflammatory, and anti-oxidative
      stress effects in diabetes mellitus (DM) rats. The underlying molecular
      mechanisms and signaling pathways of diabetic cardiomyopathy remain poorly
      understood. This study aimed to elucidate the effect of DEX on cardiac function
      in DM rats. METHODS: Eight-week-old male Sprague Dawley rats were divided into
      three groups: control (n = 5), diabetes (DM, n = 7), and diabetes + DEX (DM +
      DEX, n = 10). DM was induced via intraperitoneal injection of streptozotocin (70
      mg/kg); at 3 days later, DEX (1 ug/kg/h) was administered for 4 weeks. Cardiac
      function was evaluated using pressure-volume loop analysis and echocardiography.
      Left ventricular (LV) histological sections were used to analyze the interstitial
      collagen fraction. Using the LV samples, we performed a western blot analysis to
      evaluate signaling pathways and autophagic markers. RESULTS: The DM group had
      lower body weight and higher blood glucose level and heart weight/body weight
      ratio than the control group. However, metabolic changes did not differ between
      the DM and DM + DEX groups. Pressure-volume loop analysis and echocardiography
      showed impaired cardiac function, evidenced by a decrease in systolic and
      diastolic function, in both DM groups. DEX treatment in DM rats was associated
      with increased LV end-systolic pressure, LV contractility, cardiac output, and
      relaxed LV function compared with that in non-treated DM rats. LC3B and autophagy
      related gene (ATG) proteins increased in the hearts of DM rats compared with the
      hearts of control rats. However, DEX reduced the expression of LC3B and ATG
      proteins in the hearts of DM rats. Increased p-ERK and decreased p-AKT were
      reduced in the hearts of DEX-treated DM rats. CONCLUSIONS: DEX reduces cardiac
      dysfunction and impaired autophagy in DM rats. This study reinforces our
      understanding of the potential anti-autophagic effect of DEX in patients with
      diabetic cardiomyopathy.

PMID- 30206700
TI  - Tyrosine-hydroxylase immunoreactivity in the mouse transparent brain and adrenal
      glands.
AB  - Working on catecholamine systems for years, the neuropharmacologist Arvid
      Carlsson has made a number of important and pioneering discoveries, which have
      highlighted the key role of these neuronal and peripheral neurotransmitters in
      brain functions and adrenal regulations. Since then, major advances have been
      made concerning the distribution of the catecholaminergic systems in particular
      by studying their rate-limiting enzyme, tyrosine hydroxylase (TH). Recently new
      methods of tissue transparency coupled with in toto immununostaining and three
      dimensional (3D) imaging technologies allow to precisely map TH immunoreactive
      pathways in the mouse brain and adrenal glands. High magnification images and
      movies obtained with combined technologies (iDISCO+ and light-sheet microscopy)
      are presented in this review dedicated to the pioneer work of Arvid Carlsson and
      his collaborators.

PMID- 30206702
TI  - Coping strategies in secondary traumatization and post-traumatic growth among
      nurses working in a medical rehabilitation hospital: a pilot study.
AB  - PURPOSE: Secondary traumatization and post-traumatic growth have been recognized
      as psychological reactions that might occur among the medical staff in general,
      and among nurses in particular. Nurses in the field of medical rehabilitative
      care might reveal such reactions as their work involves stress and traumatic
      situations. Coping strategies might either alleviate or exacerbate work-related
      stress experienced by nurses. The aims of the current study were to explore the
      link between secondary traumatization and post-traumatic growth exhibited by
      nurses in the field of medical rehabilitative care, and to examine the link
      between problem-focused coping strategies and emotion-focused coping strategies
      to secondary traumatization and post-traumatic growth. MATERIAL AND METHOD: One
      hundred and fifty-three rehabilitative nurses completed self-report
      questionnaires regarding personal data, post-traumatic growth, secondary
      traumatization, ways of coping strategies and personal negative life events.
      RESULTS: Correlation matrix for the path analysis model revealed positive
      significant correlation between secondary traumatization and post-traumatic
      growth. Both, problem-focused coping and emotion-focused coping strategies were
      linked to secondary traumatization and post-traumatic growth. CONCLUSIONS: Nurses
      employed in a medical rehabilitation hospital who cope via problem-focused
      strategies as well as emotion-focused strategies in their work, might reveal
      secondary traumatization but might simultaneously benefit from post-traumatic
      growth.

PMID- 30206703
TI  - Complete nucleotide sequence of a new virus, peach chlorotic leaf spot virus,
      isolated from flat peach in China.
AB  - Contigs with sequence homologies to apple chlorotic leaf spot virus (ACLSV) were
      identified by high-throughput sequencing analysis in three peach samples.
      Complete genomic sequences of RP19-1 and RP19-2 of the virus consisted of 7,466
      and 7,465 nucleotides (nts), respectively, excluding the poly (A) tails. They
      shared the highest identity with Ta Tao 5, but lower than 70% of sequence
      similarity with other ACLSV isolates. Furthermore, phylogenetic analysis revealed
      that these two isolates clustered with Ta Tao 5, which is distinct from other
      ACLSV isolates. According to the criteria for species demarcation within the
      genus Trichovirus, these two isolates as well as Ta Tao 5 should be recognized as
      a new virus species, tentatively named "Peach chlorotic leaf spot virus".

PMID- 30206701
TI  - Prenatal stress and enhanced developmental plasticity.
AB  - Two separate lines of inquiry indicate (a) that prenatal stress is associated
      with heightened behavioral and physiological reactivity, and (b) that these
      postnatal phenotypes are associated with increased susceptibility to both
      positive and negative developmental experiences and environmental exposures. This
      research considered together raises the intriguing hypothesis first advanced by
      Pluess and Belsky (Dev Psychopathol 23:29-38, 2011) that prenatal-stress fosters,
      promotes or "programs" postnatal developmental plasticity. In this paper, we
      review further evidence consistent with this proposition, including a novel
      animal study which experimentally manipulated both prenatal stress and postnatal
      rearing. Directions for future work focused on mechanisms mediating the
      plasticity-inducing effects of prenatal stress and the moderators of such effects
      are outlined.

PMID- 30206705
TI  - Serotonergic neuron ADF modulates avoidance behaviors by inhibiting sensory
      neurons in C. elegans.
AB  - Serotonin plays an essential role in both the invertebrate and vertebrate nervous
      systems. ADF, an amphid neuron with dual ciliated sensory endings, is considered
      to be the only serotonergic sensory neuron in the hermaphroditic Caenorhabditis
      elegans. This neuron is known to be involved in a range of behaviors including
      pharyngeal pumping, dauer formation, sensory transduction, and memory. However,
      whether ADF neuron is directly activated by environmental cues and how it
      processes these information remains unknown. In this study, we found that ADF
      neuron responds reliably to noxious stimuli such as repulsive odors, copper,
      sodium dodecyl sulfonate (SDS), and mechanical perturbation. This response is
      mediated by cell-autonomous and non-cell autonomous mechanisms. Furthermore, we
      show that ADF can modulate avoidance behaviors by inhibiting ASH, an amphid
      neuron with single ciliated ending. This work greatly furthers our understanding
      of 5-HT's contributions to sensory information perception, processing, and the
      resulting behavioral responses.

PMID- 30206704
TI  - Mycorrhizal microbiomes.
AB  - This Mycorrhiza issue groups topical papers based on presentations and
      discussions at the Mycorrhizal Microbiomes session at 9th International
      Conference on Mycorrhiza, Prague, Czech Republic, August 2017. The five articles
      that appear in this special issue advance the field of mycorrhizal microbiomes,
      not simply by importing ideas from an emerging area, but by using them to inform
      rich and methodologically grounded research. The aim of this special issue is to
      explore the interactions between mycorrhizal fungi and surrounding complex
      environments from a distinct but complementary point of view, highlighting the
      large spectrum of unknowns that still need to be explored. In this editorial, we
      first introduce the level of knowledge in this thematic area, then describe major
      results from the five manuscripts and characterise their importance to
      mycorrhizal research, and finally discuss the developing topics in this rapidly
      emerging thematic area.

PMID- 30206707
TI  - Regulation of glucose and lipid metabolism by the pancreatic and extra-pancreatic
      actions of taurine.
AB  - The beneficial actions of L-taurine (Tau) against glucose intolerance, obesity,
      type 2 diabetes (T2D), and non-alcoholic fat liver disease (NAFLD) have been
      linked to its antioxidant and anti-inflammatory effects, which ameliorate tissue
      insulin sensitivity. Importantly, there are several lines of evidence that
      indicate a direct action of Tau on the endocrine pancreas to regulate the
      secretion and paracrine actions of insulin, glucagon, and somatostatin.
      Furthermore, Tau can also ameliorate glucose metabolism through the enhancement
      of insulin signaling. However, some of the benefits of Tau upon intermediary
      metabolism may manifest via considerable antagonism of the action of insulin.
      Therefore, this review discusses the mechanisms of action by which Tau may
      regulate endocrine pancreatic morphofunction, and glucose and lipid homeostasis.

PMID- 30206708
TI  - The effect of an oral care protocol and honey mouthwash on mucositis in acute
      myeloid leukemia patients undergoing chemotherapy: a single-blind clinical trial.
AB  - OBJECTIVES: The purpose of the study is to evaluate and compare the effectiveness
      of honey mouthwash and an oral care protocol on mucositis and weight loss in
      patients with acute myeloid leukemia receiving chemotherapy. MATERIALS AND
      METHODS: In this single-blind clinical trial, 53 acute myeloid leukemia (AML)
      patients receiving chemotherapy were randomly assigned into three groups: honey
      mouthwash (n = 17), oral care (n = 17), and control (n = 19). The severity of
      mucositis and weights was examined blindly at the baseline and 4-week follow-up.
      RESULTS: The prevalence of grades of mucositis in the study groups was
      significant at the end of the third (p = 0.002) and fourth (p < 0.001) weeks. The
      mucositis severity decreased at the end of the third and fourth weeks in the
      honey mouthwash group (p < 0.05), whereas it increased in the control group (p <
      0.001). The difference in the weight was significant between the honey mouthwash
      and the control groups (p < 0.05, MD = 1.95) at the end of the third week, and
      between the honey mouthwash group with the control (p < 0.01, MD = 2.92) and oral
      care groups (p < 0.05, MD = 1.95) at the end of the fourth week. CONCLUSIONS:
      Honey mouthwash is effective in preventing and reducing the severity of
      mucositis, and weight loss and can be recommended for patients undergoing
      chemotherapy. CLINICAL RELEVANCE: The results of this study suggest that honey
      mouthwash can reduce the incidence and severity of mucositis in patients, reduce
      or eliminate the possibility of weight loss in them, as well as encourage some
      weight gain. Compared to routine oral care, honey mouthwash is also easier to use
      and handle. TRIAL REGISTRATION: IRCT2015121419919N7.

PMID- 30206711
TI  - Correlation between magnetic resonance imaging (MRI) findings and the new bone
      formation factor Dkk-1 in patients with spondyloarthritis.
AB  - In recent years, MRI has been regarded as a major diagnostic tool for
      spondyloarthritis (SpA), and anti-TNF therapy has been widely confirmed as an
      effective treatment strategy. This study was designed to investigate the
      correlation between the secreted protein dickkopf-1 (Dkk-1) and abnormal findings
      on magnetic resonance imaging (MRI) through a prospective study of 30 cases of
      SpA. Thirty patients with active SpA were included, all treated with recombinant
      human tumor necrosis factor (TNF) receptor-antibody fusion protein (YiSaiPu)
      injection at 50 mg/week for 6 months. All patients were also examined for their
      clinical, serological, and imaging manifestations of the condition before and
      after treatment. In patients receiving TNF inhibitor treatment, the erythrocyte
      sedimentation rate (ESR), C-reactive protein (CRP), and clinical activity indices
      BASDAI, BASFI, BASMI, ASDAS-CRP were significantly decreased (p < 0.01). Serum
      Dkk-1 concentration was also significantly decreased (p < 0.05), as were the
      scores of bone marrow edema of the sacroiliac joints and the spine (p < 0.05).
      The score of sacroiliac joint backfill was significantly increased (p < 0.05),
      and the baseline and changes in the serum Dkk-1 concentration were significantly
      correlated with the baseline and changes in spinal bone marrow edema levels.
      Inhibition of the level of serum Dkk-1 by TNF inhibitors may be the molecular
      basis for inhibiting the formation of new bone in SpA patients. In addition,
      spinal marrow edema may have significance for predicting new bone formation.

PMID- 30206706
TI  - 1,8-Cineole blocks voltage-gated L-type calcium channels in tracheal smooth
      muscle.
AB  - 1,8-Cineole is a cyclic monoterpenoid used in folk medicine for treatment of
      numerous respiratory diseases and other infections. 1,8-Cineole has anti
      inflammatory, antioxidant, and myorelaxant effects, as well as low toxicity. In
      the present study, the effects of 1,8-cineole on contractility and voltage-gated
      calcium channels (VGCC) in tracheal smooth muscle were investigated. Intact and
      dissociated tracheal smooth muscle were used for muscle contraction and patch
      clamp recordings, respectively. In experiments involving muscle contraction, 1,8
      cineole potentiated contractions at low concentrations and relaxed contractions
      induced by isotonic K+ at high concentrations. AMTB (a TRPM8 channel blocker)
      reduced the potentiation induced by 1,8-cineole while indomethacin (a COX
      inhibitor) did not block this effect. In dissociated myocytes, 1,8-cineole
      partially blocked Ba2+ currents through VGCC in a concentration-dependent manner.
      1,8-Cineole shifted the steady-state activation and inactivation curves to the
      left and also reduced the current decay time constant. In conclusion, 1,8-cineole
      has a dual effect on tracheal smooth muscle contraction resulting in a biphasic
      effect. Our data suggest that the potentiation effect is mediated by activation
      of TRPM8 channels and the relaxation effect is mediated by the blockage of L-type
      VGCC.

PMID- 30206714
TI  - Ppargamma Is Involved in the Transcriptional Regulation of Liver LC-PUFA
      Biosynthesis by Targeting the Delta6Delta5 Fatty Acyl Desaturase Gene in the
      Marine Teleost Siganus canaliculatus.
AB  - As the first marine teleost demonstrated to have the ability of long-chain
      polyunsaturated fatty acids (LC-PUFA) biosynthesis from C18 PUFA precursors, the
      rabbitfish Siganus canaliculatus provides us a unique model for clarifying the
      regulatory mechanisms of LC-PUFA biosynthesis in teleosts aiming at the
      replacement of dietary fish oil (rich in LC-PUFA) with vegetable oils (rich in
      C18 PUFA precursors but devoid of LC-PUFA). In the study of transcription
      regulation of gene encoding the Delta6Delta5 fatty acyl desaturase (Delta6Delta5
      Fads), a rate-limiting enzyme catalyzing the first step of LC-PUFA biosynthesis
      in rabbitfish, a binding site for the transcription factor (TF), peroxisome
      proliferator-activated receptor gamma (Ppargamma), was predicted in Delta6Delta5
      fads2 promoter by bioinformatics analysis, and thus the present study focused on
      the regulatory roles of Ppargamma on Delta6Delta5 fads2. First, the activity of
      the Delta6Delta5 fads2 promoter was proved to be downregulated by ppargamma
      overexpression and upregulated by treatment of Ppargamma antagonist (GW9662),
      respectively, in HEK 293T cells with the dual luciferase reporter assay.
      Ppargamma was further confirmed to interact with the promoter by electrophoretic
      mobility shift assay. Moreover, in S. canaliculatus hepatocyte line (SCHL) cells,
      GW9662 decreased the expression of ppargamma together with increase of
      Delta6Delta5 fads2 mRNA. Besides, Delta6Delta5 fads2 expression was increased by
      ppargamma RNAi knockdown and reduced by its mRNA overexpression. Furthermore,
      knockdown of ppargamma induced a high conversion of 18:3n-3 to 18:4n-3 and 18:2n
      6 to 18:3n-6, while ppargamma mRNA overexpression led to a lower conversion of
      that, and finally a significant decrease of 20:4n-6(ARA), 20:5n-3(EPA), and 22:6n
      3(DHA) production. The results indicate that Ppargamma is involved in the
      transcriptional regulation of liver LC-PUFA biosynthesis by targeting
      Delta6Delta5 fads2 in rabbitfish, which is the first report of Ppargamma
      involvement in the regulation of LC-PUFA biosynthesis in teleosts.

PMID- 30206712
TI  - Evaluating the Use of 18F-FDG PET CT for External Beam Radiotherapy Planning in
      Gynaecological Malignancies.
AB  - PURPOSE OF REVIEW: To evaluate the evidence for the use of fluorine-18
      fluorodeoyglucose (18F-FDG) PET CT in external beam radiotherapy planning for
      treatment of gynaecological malignancies. RECENT FINDINGS: Our review confirms
      that the incorporation of 18F-FDG PET CT during radiotherapy planning may
      decrease inter-observer variability during target delineation. It can also
      provide useful functional information regarding the tumour, which may facilitate
      the development of techniques for dose escalation and 'dose painting' not only
      for primary disease, especially in cervical cancer, but also nodal metastasis.
      The utilisation of this functional modality in external beam radiotherapy
      planning, particularly in locally advanced cervical malignancy, is an exciting
      topic that warrants further prospective research. Perhaps the most valuable role
      may be the potential to deliver dose escalation to 18F-FDG PET CT avid targets
      previously limited by organ at risk constraints, now that we have significantly
      more advanced radiotherapy planning tools at our disposal.

PMID- 30206715
TI  - Mapping tidal channel dynamics in the Sundarbans, Bangladesh, between 1974 and
      2017, and implications for the sustainability of the Sundarbans mangrove forest.
AB  - This study presents the spatial and temporal dynamics of tidal channels in the
      Bangladesh Sundarbans. Parts of the Passur River system were considered for this
      investigation. Tidal channel bank layers were extracted from aerial photographs
      from 1974 and 2011 and a Sentinel-2 image from 2017. On-screen digitizing of a
      tidal channel was undertaken to create the tidal channel layers, and special care
      was taken during digitization to obtain more accurate results. Layers were
      overlaid together so that the tidal channel position could be seen for each date.
      Tidal channel positions were highlighted to infer the erosion/accretion sectors
      along the channel, and the tidal channel dynamics were calculated. Remote sensing
      and Geographic Information System (GIS) platforms were used to analyse, interpret
      and visualize data on accretion and erosion, as well as the locations of the
      tidal channel bank over different years. The results revealed that erosion was
      severe in the larger channels, whereas accretion was dominant in the smaller
      channels. These erosion and accretion processes played an active role in the
      displacement of tidal channel banks during the period under investigation.
      Displacement of the tidal channel bank has had a profound impact on the
      Sundarbans mangrove ecosystem, and continued erosion and accretion processes are
      of concern for the future sustainability of biodiversity in the Sundarbans. While
      in the short term, these changes may not have much impact; over decades, the
      dynamics of tidal channels may significantly contribute to the imbalance of fauna
      and flora in the Sundarbans.

PMID- 30206710
TI  - Genetic variations using whole-exome sequencing might predict response for
      neoadjuvant chemoradiotherapy in locally advanced rectal cancer.
AB  - A good pathologic response to neoadjuvant chemoradiotherapy (CRT) in locally
      advanced rectal cancer (LARC) is associated with a better prognosis. However,
      there is no effective method to predict CRT response in LARC patients. Therefore,
      this study used whole-exome sequencing (WES) to identify novel biomarker
      predicting CRT benefit in LARC. Two independent tumor tissue sets were used to
      evaluate the genetic differences between the good CRT response group (15 patients
      achieved a pathologic complete response (pCR)) and the poor CRT response group
      (15 patients with pathologic stage III). After applying WES to the discovery set
      of 30 patients, additional samples (n = 67) were genotyped for candidate variants
      using TaqMan or Sanger sequencing for validation. Overall, this study included a
      total of 97 LARC patients. In the discovery and validation set, there was no
      known genetic mutation to predict response between two groups, while five
      candidate variants (BCL2L10 rs2231292, DLC1 rs3816748, DNAH14 rs3105571, ITIH5
      rs3824658, and RAET1L rs912565) were found to be significantly associated with
      pCR. In the dominant model, the GC/CC genotype of DLC1 rs3816748 (p = 0.032),
      AC/CC genotype of DNAH14 rs3105571 (p = 0.009), and TT genotype of RAET1 rs912565
      (p < 0.0001) were associated with a higher pCR rate. In the recessive model,
      BCL2L10 rs2231292 (p = 0.036) and ITIH5 rs3824658 (p = 0.003) were significantly
      associated with pCR. In the co-dominant model, 4 candidate variants (DLC1
      rs3816748, DNAH14 rs3105571, ITIH5 rs3824658, and RAET1L rs912565) were
      significantly correlated with pCR. However, none of the candidate variants was
      associated with relapse-free or overall survival. The present results suggest
      that genetic variations of the BCL2L10 rs2231292, DLC1 rs3816748, DNAH14
      rs3105571, ITIH5 rs3824658, and RAET1L rs912565 genes can be used as biomarkers
      predicting the CRT response for patients with LARC.

PMID- 30206713
TI  - Use of MR Urography in Pediatric Patients.
AB  - PURPOSE OF REVIEW: In this article, we describe the basics of how magnetic
      resonance urography (MRU) is performed in the pediatric population as well as the
      common indications and relative performance compared to standard imaging
      modalities. RECENT FINDINGS: Although MRU is still largely performed in major
      academic or specialty imaging centers, more and more applications in the
      pediatric setting have been described in the literature. MRU is a comprehensive
      imaging modality for evaluating multiple pediatric urologic conditions combining
      excellent anatomic detail with functional information previously only available
      via renal scintigraphy. While generally still reserved for problem solving, MRU
      should be considered for some conditions as an early imaging technique.

PMID- 30206709
TI  - Graded Combined Aerobic Resistance Exercise (CARE) to Prevent or Treat the
      Persistent Post-concussion Syndrome.
AB  - PURPOSE OF REVIEW: To review the growing body of indirect and direct evidence
      that suggests that exercise can be helpful for children, adolescents, and adults
      with persistent symptoms following a mild traumatic brain injury (mTBI). RECENT
      FINDINGS: The direct evidence shows that graded exercise assessments are safe,
      and that aerobic exercise interventions are associated with improvement of
      multiple symptoms and other benefits, including earlier return-to-sport. The
      indirect evidence supports this approach via studies that reveal the potential
      mechanisms, and show benefits for related presentations and individual symptoms,
      including headaches, neck pain, vestibular problems, sleep, stress, anxiety, and
      depression. We document the forms of exercise used for the post-acute management
      of mTBI, highlight the knowledge gaps, and provide future research directions. We
      recommend trialing a new approach that utilizes a graduated program of
      individually prescribed combined aerobic resistance exercises (CARE) if mTBI
      symptoms persist. This program has the potential to improve patient outcomes and
      add to the management options for providers.

PMID- 30206717
TI  - Model and movement: studying cell movement in early morphogenesis, 1900 to the
      present.
AB  - Morphogenesis is one of the fundamental processes of developing life.
      Gastrulation, especially, marks a period of major translocations and bustling
      rearrangements of cells that give rise to the three germ layers. It was also one
      of the earliest fields in biology where cell movement and behaviour in living
      specimens were investigated. This article examines scientific attempts to
      understand gastrulation from the point of view of cells in motion. It argues that
      the study of morphogenesis in the twentieth century faced a major dilemma, both
      epistemological and pictorial: representing form and understanding movement are
      mutually exclusive, as are understanding form and representing movement. The
      article follows various ways of modelling, imaging, and simulating gastrular
      processes, from the early twentieth century to present-day systems biology. The
      first section examines the tactile modelling of shape changes, the second cell
      cinematography, mainly the pioneering work of the German embryologists Friedrich
      Kopsch and Ernst Ludwig Graper in the 1920s but also a series of classic, yet not
      widely known, studies of the 1960s. The third section deals with the changes that
      computer simulation and live-cell imaging introduced to the modelling of shape
      change and the study of cell movement at the turn of the twenty-first century.
      Although live-cell imaging promises to experiment upon and represent the living
      body simultaneously, I argue that the new visuals are an obstacle rather than a
      solution to the puzzle of understanding cell motion.

PMID- 30206716
TI  - The critical role of comorbidities and polypharmacy in lower risk myelodysplastic
      patients: is there any difference between countries?

PMID- 30206719
TI  - Radioactive Iodine-Refractory Differentiated Thyroid Cancer in the Elderly.
AB  - : Most common thyroid cancers are differentiated thyroid cancers (DTCs) and have
      papillary, follicular, or Hurthle cell morphology. Papillary thyroid carcinoma
      (PTC) is the most common malignant tumor of the thyroid gland. The incidence of
      DTC increases with age. While most of the patients with DTC have an excellent
      prognosis, the outcome can be poor when diagnosed in elderly patients. PURPOSE OF
      REVIEW: Current treatment approach for DTC includes surgery, thyroid-stimulating
      hormone (TSH) suppression, radioactive iodine, external beam radiotherapy, or
      systemic treatments such as kinase inhibitors. Radioactive iodine therapy (RAI)
      is the primary first-line systemic treatment for advanced DTC. However, during
      the course of treatment, the tumor may become refractory to RAI. Elderly patients
      are more likely to be diagnosed with advanced disease that can be refractory to
      RAI. RECENT FINDINGS: The advent of TKIs (tyrosine kinase inhibitors) and their
      usage in RAI refractory disease has shown improved progression-free survival.
      These agents are, however, associated with increased toxicity. The variable
      nature of disease and toxicity associated with the systemic therapy makes it
      important to have an individualized approach to management, especially in the
      elderly population who can be more susceptible to toxicities.

PMID- 30206718
TI  - Food Allergies Caused by Allergenic Lipid Transfer Proteins: What Is behind the
      Geographic Restriction?
AB  - PURPOSE OF REVIEW: To critically examine evidence suggesting that food allergy
      induced by lipid transfer proteins (LTPs) follows a geographic pattern. RECENT
      FINDINGS: LTP syndrome remains most common in the Mediterranean basin, with a
      clear gradient seen in prevalence of LTP sensitization between northern and
      southern Europe. We hypothesize that high levels of birch pollen seem to protect
      against LTP allergy, as these higher levels correlate with a lower prevalence of
      LTP hypersensitivity. Nevertheless, LTP food allergy cases still appear in areas
      having a high environmental level of birch pollen. Food allergy caused by LTP may
      be related to (1) primary sensitization to a food LTP allergen in the absence of
      pollinosis, (2) primary sensitization to LTP from a pollen source, and (3) co
      sensitization to LTP from pollen and food.

PMID- 30206728
TI  - Prolonging the duration of post-infusion scalp cooling in the prevention of
      anthracycline-induced alopecia: a randomised trial in patients with breast cancer
      treated with adjuvant chemotherapy.
AB  - PURPOSE: Scalp cooling as a method to reduce the incidence of chemotherapy
      induced alopecia (CIA) is increasingly used in daily practice worldwide. However,
      in patients treated with 5-fluorouracil, epirubicin and cyclophosphamide (FEC),
      scalp cooling fails in 48-67% of patients. This study investigated the efficacy
      of extended duration of post-infusion scalp cooling in breast cancer patients
      treated with this regimen. METHODS: In this prospective multi-centre randomised
      study, 102 patients with early breast cancer treated with adjuvant FEC
      chemotherapy were randomly assigned in a 1:1 ratio to a post-infusion cooling
      time of 90 or 150 min. The primary endpoint was the need to wear a wig or other
      head covering to mask visible hair loss. RESULTS: Sixteen out of 48 patients
      (33%) treated with 90 min of post-infusion cooling did not need any head
      covering, compared with 21 out of 46 patients (45%) treated with 150 min of post
      infusion cooling (p = 0.2). WHO grades 2-3 (moderate-complete) alopecia were
      reported more often in patients treated with 90-min post-infusion cooling time (n
      = 25/51 (49%) versus n = 17/51 (33%); p = 0,02). Scalp cooling was well-tolerated
      (mean Visual Analogue Score 7.4) and only three patients (3%) stopped due to
      intolerance during treatment. CONCLUSIONS: Extending the duration of 90-min post
      infusion scalp cooling to 150 min in patients treated with adjuvant FEC
      chemotherapy was well-tolerated but did not significantly diminish the need for
      head covering. However, grades 2-3 alopecia was seen less often with prolonged
      post-infusion scalp cooling.

PMID- 30206723
TI  - Inaugural cognitive decline, late disease onset and novel STUB1 variants in
      SCAR16.

PMID- 30206721
TI  - A Novel Method of Segmentation and Classification for Meditation in Health Care
      Systems.
AB  - Meditation improves positivity in behavioral as well as psychological changes,
      which are brought elucidated by knowing neuro-physiological consequences of
      meditation. In the field of cognitive science, neuroscience and physiological
      research, Electroencephalogram (EEG) is extensively utilized. The primary tasks
      of EEG signal analysis is to identify the noisy signal as well as enormous data
      that create signal processing and subsequent analysis. Beforehand any analysis of
      the EEG signal, the obtained raw signal must be preprocessed for eliminating
      undesirable artifacts as well as horrible noise. With the aim of resolving this
      issue, in this research, raw signals are preprocessed with the help of Band-Pass
      Filter (BPF) for noise removal method. Instead, in adaptive Sliding Window with
      Fuzzy C Means Clustering (SW-FCM) segmentation is presented, which precisely as
      well as automatically segments the signals. So as to analyze the accuracy, five
      features such as electroencephalography alpha spectrum, frequency of the main
      peak, Amplitude of the main peak, Higher Order Crossing (HOC), and wavelet
      features are used as the evaluating variables. Lastly to assess the meditation
      experience with Fuzzy Kernel least square Support Vector Machine (FKLSSVM)
      classifier, the presented method with a cross-sectional analysis is utilized.
      These two classifiers are utilized for meditation experience classification by
      utilizing an individual feature vector values from equivalent EEG signals. The
      dataset samples are gathered from Open source Brain-Computer Interface (Open BCI)
      platform. Outcomes attained are matched up for diverse techniques for identifying
      as well as for classifying signal segments features using MATLAB. Presented
      classifiers of the meditation process validate quick interpretation methods that
      differentiate meditation experience and valuable performance related to
      artificial approaches for the big-data analysis.

PMID- 30206726
TI  - Development of Measure Yourself Concerns and Wellbeing for informal caregivers of
      people with cancer-a multicentred study.
AB  - PURPOSE: Measure Yourself Concerns and Wellbeing (MYCaW) is a validated person
      centred measure of the concerns and wellbeing of people affected by cancer.
      Research suggests that the concerns of informal caregivers (ICs) are as complex
      and severely rated as people with cancer, yet MYCaW has only been used to
      represent cancer patients' concerns and wellbeing. This paper reports on the
      development of a new qualitative coding framework for MYCaW to capture the
      concerns of ICs, to better understand the needs of this group. METHODS: This
      multicentred study involved collection of data from ICs receiving support from
      two UK cancer support charities (Penny Brohn UK and Cavendish Cancer Care).
      Qualitative codes were developed through a detailed thematic analysis of ICs'
      stated concerns. RESULTS: Thematic analysis of IC questionnaire data identified
      key themes which were translated into a coding framework with two overarching
      sections; (1) 'informal caregiver concerns for self' and (2) 'informal caregiver
      concerns for the person with cancer'. Supercategories with specific accompanying
      codes were developed for each section. Two further rounds of framework testing
      across different cohorts allowed for iterative development and refinement of the
      framework content. CONCLUSIONS: This is the first person-centred tool
      specifically designed for capturing IC's concerns through their own words. This
      coding framework will allow for IC data to be analysed using a rigorous and
      reproducible method, and therefore reported in a standardised way. This may also
      be of interest to those exploring the needs of ICs of people in other situations.

PMID- 30206725
TI  - The role of the Patient-Generated Subjective Global Assessment (PG-SGA) and
      biochemical markers in predicting anemia patients with cancer.
AB  - PURPOSE: The causes of anemia and the common side effects of cancer are
      multifactorial. Malnutrition is one of the alleged components of the
      aforementioned complications. This study planned to investigate the relationship
      among biochemical markers, Patient-Generated Subjective Global Assessment (PG
      SGA), and anemia in cancer patients. METHODS: This analysis consisted of 234
      patients who were enlisted in the Department of Oncology of the First Hospital of
      Shanxi Medical University between December 2016 and October 2017. The groups were
      divided into anemic and non-anemic patients. The gathered data primarily
      discussed the patients' basic information, specifically the age, gender, smoking,
      alcohol consumption, and nutritional status based on levels of serum biochemical
      markers and PG-SGA scores. RESULTS: Among the participants, 31.2% of the cancer
      patients were diagnosed with anemia whereas, according to the scores of PG.SGA,
      65.0% of patients experienced malnourishment. The anemia was significantly
      associated with biochemical markers, expecting a transferrin in univariable
      analyses. Binary logistic regression analysis between anemic cancer patients and
      non-anemic cancer patients suggested that high PG-SGA score (odds ratio 1.082;
      95% CI 1.027-1.141) implied the risk factor for anemia, and high PG-SGA scores
      could potentially increase the risk of anemia. The multiple regression analysis
      showed that hemoglobin concentration (OR 0.575; 95% CI 0.450-0.736) and PG-SGA
      score (OR 1.231; 95% CI 1.013-1.496) were linked to anemia. However, total
      protein, albumin, prealbumin, serum iron, transferrin, and transferrin saturation
      lacked a strong relationship with anemia. CONCLUSION: Anemia prevailed in cancer
      patients, as nutritionally assessed by PG-SGA, while hemoglobin established a
      linkage with anemia as they could provide extra predictive information about
      anemia in patients diagnosed with cancer.

PMID- 30206727
TI  - Construction of new personal meanings by cancer patients: a qualitative analysis
      in an Italian patient population.
AB  - PURPOSE: The goal of this study is to investigate the meaning that cancer
      patients in active therapy and/or rehabilitation give to their illness and
      resources they rely on to build new experiences of meaning and a future
      perspective. METHODS: The present study consisted in a summative content analysis
      of answers to open questions of the Purpose In Life (PIL) Questionnaire
      administered to 158 consecutive patients with non-advanced cancer (no
      metastases). The PIL is an attitude scale that indicates the degree of attainment
      of meaning and purpose in life and is divided into three sections: a first 20
      item quantitative section, with statements rated on a 7-point verbal scale with
      two anchoring phrases (part A); a qualitative section with 13 open-end items and
      paragraph composition section addressing the future goals (part B) and past
      meaningful experience (part C). For the present study, we analyzed the answers to
      open questions, most interesting in a therapeutic contest related to the meanings
      associated with life, illness, and suffering to understand the experienced of the
      cancer patients. RESULTS: The main recurring themes in PIL section B analyzed
      associated to the sense of life, disease, and death are as follows: meaning
      (positive/negative), personal dimension, religiousness; physical health, family,
      normal life; negative sense of death, the end, natural transition, religious
      belief, consolation, mystery, rejection; opportunity, negativity. Whereas main
      themes emerging from section C were associated to life goals of the interviewed
      patients: the desire of realization in the future perspective; the value of life;
      physical health and healing; guiding values; plus three more themes,
      distinguishable, but with a minor recurrence: legacy responsibility,
      religiousness, lack of purpose/resignation. CONCLUSION: The use of summative
      content analysis evidenced the recurrence of a strong sense of positivity,
      present in the majority of the interviews. In particular, this positivity is
      shown by the use of words associated frequently to self-consciousness and self
      evaluation, desire of happiness, and desire of contributing to the good of
      significant others and of taking care of your own life in order to give a
      positive contribution.

PMID- 30206722
TI  - The Role of the Specialist Nurse in Gynaecological Cancer.
AB  - PURPOSE OF REVIEW: To explore the role of the specialist nurse within
      gynaecological cancer. RECENT FINDINGS: There are many different job titles
      associated with the role of the specialist nurse. Nursing roles are evolving not
      only to meet the increasing demands on services but also within the ever changing
      landscape of cancer treatments and improvement in survival. Women and their
      families need specialist nurses to guide and support them on their cancer
      journey, along the treatment trajectory and into survivorship. This paper
      explores specialist nurse roles generally, and within our service which have been
      adapted to meet service and patient needs within a gynaecological cancer centre.
      Irrelevant of title, specialist nurses are best suited to meet the patients'
      needs. The fundamental ethos of the care should always remain having the
      patients' best interest at heart, acting as their advocate - in essence giving
      them a voice when they need it.

PMID- 30206724
TI  - Memory formation in cyclically deformed amorphous solids and sphere assemblies.
AB  - We study a model amorphous solid that is subjected to repeated athermal cyclic
      shear deformation. It has previously been demonstrated that the memory of the
      amplitudes of shear deformation the system is subjected to (or trained at) is
      encoded, and can be retrieved by subsequent deformation cycles that serve as read
      operations. Here we consider different read protocols and measurements and show
      that single and multiple memories can be robustly retrieved through these
      different protocols. We also show that shear deformation by a larger amplitude
      always erases the stored memories. These observations are similar to those in
      experiments with non-Brownian colloidal suspensions and corresponding models, but
      differ in the possibility of storing multiple memories non-transiently. Such a
      possibility has been associated with the presence of cycles of transitions that
      take place in the model amorphous solids, between local energy minima. Here, we
      also study low-density sphere assemblies which serve as models for non-Brownian
      colloidal suspensions, under athermal deformation, and identify a regime where
      the signatures of memory encoding are similar to the model glass, even when
      transition between local energy minima are absent. We show that such a regime
      corresponds to the presence of loop reversibility, rather than point
      reversibility of configurations under cyclic deformation.

PMID- 30206720
TI  - Detection and assessment of the phytotoxicity of residual organic pollutants in
      sediment contaminated with pulp and paper mill effluent.
AB  - The safe disposal of pulp and paper mill effluent is still a threat to the
      environment due to the presence of several unknown organic pollutants. The
      comparative physico-chemical analysis of pulp and paper mill effluent
      contaminated sediment (PPECS) of site 1 and site 2 showed that the sediment had
      an alkaline nature and was loaded with several organic pollutants and heavy
      metals. SEM-EDX examination showed a porous structure with a heterogeneous
      distribution of particles, allowing the adsorption of metal and other complex
      organic ions. FTIR analysis depicted the presence of a variety of functional
      groups, i.e., alkyl halides, phenolics, and lignin, in the contaminated sediment.
      GC-MS analysis showed the major presence of organic pollutants, i.e., 2-methyl-4
      keto-2-pentan-2-ol and 3,7-dioxa-2,8-disilanonane,2,2,8,8-tetramethyl-5
      [(trimethylsilyl)oxy], in the site 1 sediment contaminated with pulp and paper
      mill waste, while 2-methyl-4-keto-2-trimethylsiloxypentane, 4-ethyl-2
      methoxyphenol, ethyl-2-octynoate, cis-9-hexadecenoic acid, and octadecenoic acid
      were detected in the site 2 sediment contaminated with pulp and paper mill waste.
      The genotoxicity of PPECS determined by examining Allium cepa root cell division
      showed chromosomal aberration. In this study, several compounds that have not
      been reported before were identified.

PMID- 30206729
TI  - Using drug-loaded pH-responsive poly(4-vinylpyridine) microspheres as a new
      strategy for intelligent controlling of Lactobacillus plantarum contamination in
      bioethanol fermentation.
AB  - Bioethanol fermentation is usually contaminated by bacteria, especially lactic
      acid bacteria (LAB), thereby leading to decrease of bioethanol yield and serious
      economic losses. Nisin is safer for controlling of bacterial contamination than
      antibiotics that are widely applied in industry. Moreover, in LAB contaminative
      bioethanol fermentation system, consistently decreased pH value provides
      opportunity to realize pH value responsive material-based release of anti
      bacteria substances for intelligent and persistent controlling of bacterial
      contamination. In this study, nisin was embedded into pH-sensitive poly(4
      vinylpyridine) (P4VP) microspheres synthesized by suspension polymerization to
      realize intelligent controlling of Lactobacillus plantarum contamination in
      bioethanol fermentation. Chloramphenicol with the highest antimicrobial activity
      and excellent stability was chosen as the model drug to be embedded into P4VP
      microspheres to test the drug release behavior. The drug release curve of
      chloramphenicol-loaded P4VP microspheres showed sustained and pH-responsive
      release properties. The diameters of the microspheres ranged from 40 to 100 um.
      The encapsulation efficiency of nisin into P4VP microspheres was 47.67% and the
      drug-loading capacity of nisin was 2.5%. Nisin-loaded P4VP microspheres were
      added into the simulated contaminative fermentation system, and successfully
      reversed the decline of bioethanol yield secondary to L. plantarum contamination.
      The results in this study indicated that L. plantarum contamination in bioethanol
      fermentation could be effectively controlled by nisin-loaded P4VP microspheres.

PMID- 30206731
TI  - Effect of Helicobacter pylori eradication on the incidence of gastric cancer: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Helicobacter pylori (H. pylori) is considered to be the most
      important risk factor for gastric cancer (GC). The International Agency for
      Research on Cancer reported that H. pylori eradication could reduce the risk of
      developing GC. Several clinical studies have investigated this relationship as
      well; however, their results are inconsistent owing to the varied inclusion
      criteria. To address the effect of H. pylori eradication on GC incidence, we
      conducted a comprehensive meta-analysis with several subgroup analyses to resolve
      these inconsistencies. METHODS: We searched MEDLINE and Ichushi-Web to identify
      randomized control trial and cohort study articles (English or Japanese) through
      December 2016. Manual searches were also conducted to identify unlisted
      references in these databases. Eligible studies reported GC incidence as an
      outcome, with comparisons between H. pylori eradication and control groups.
      Subgroup analyses were conducted by country, conditions at baseline, and follow
      up periods. RESULTS: We selected 28 studies among 1583 references in the
      databases and 4 studies by manual searches. The H. pylori eradication group
      showed significantly lower risk of GC [odds ratio (OR) 0.46; 95% confidence
      interval 0.39-0.55]. The subgroup analyses indicated that the beneficial effect
      of eradication was greater in Japan (OR 0.39; 95% CI 0.31-0.49), particularly
      among those with benign conditions (OR 0.32; 95% CI 0.19-0.54), although none of
      them was statistically significant. However, reduction of gastric cancer after
      eradication was significantly greater (p = 0.01) in the groups with long-term (5
      years or longer) follow-up (OR 0.32; 95% CI 0.24-0.43) as compared to those with
      shorter follow-up (less than 5 years) (OR 0.55; 95% CI 0.41-0.72). CONCLUSION:
      Real world data showed that large-scale eradication therapy has been performed
      mostly for benign conditions in Japan. Since eradication effects in preventing
      gastric cancer are conceivably greater there, GC incidence may decline faster in
      Japan than expected from the previous meta-analyses data which were based on
      multi-national, mixed populations with differing screening quality and disease
      progression.

PMID- 30206734
TI  - Physical plasma: a new treatment option in gynecological oncology.
AB  - Non-thermal application of physical plasma is rapidly gaining importance for the
      future therapy and prevention of chronic inflammatory diseases and tumors. Here,
      we outline the importance of this innovative and less invasive therapy option,
      particulary for the treatment and prevention of gynecological cancers.

PMID- 30206735
TI  - Roles of SIRT1/FoxO1/SREBP-1 in the development of progestin resistance in
      endometrial cancer.
AB  - PURPOSE: The prevalence of endometrial cancer (EC) is increasing worldwide.
      Progestin therapy is effective for both early stage EC patients who require
      preserving fertility and advanced or recurrent patients. Progestin resistance
      resulting from downregulation of progesterone receptor (PR) remains a major
      problem, and its mechanism is currently unclear. It was demonstrated that Sirtuin
      1 (SIRT1), forkhead transcription factor 1 (FoxO1) and sterol regulatory element
      binding protein-1 (SREBP-1) may act as a pathway and play crucial roles in the
      development of EC in our previous studies. In the present study, we investigated
      the effect on the development of progestin resistance and the relationship with
      PR of SIRT1/FoxO1/SREBP-1. METHODS: A progestin-resistant Ishikawa cell line was
      established in the stimulation and selection of medroxyprogesterone acetate
      (MPA), and the resistance was analyzed by MTT assay, flow cytometry, and
      Transwell invasion assay. qRT-PCR and western blotting were conducted to detect
      the expression of SIRT1, FoxO1, SREBP-1 and PR. SIRT1 knockdown progestin
      resistant cells were established by lentiviral transduction. RESULTS: The new
      progestin-resistant cell line presented sufficient resistance to MPA in aspects
      of proliferation, distribution of cell cycle and apoptosis compared with original
      Ishikawa cells. Besides, the invasion capability of progestin-resistant cells was
      observably increased. In both protein and mRNA levels, SIRT1 and SREBP-1 were
      upregulated in progestin-resistant cells, while PR and FoxO1 were downregulated.
      SIRT1 was knocked down by lentivirus transfection in progestin-resistant cells,
      resulting in upregulation of PR, FoxO1 and downregulation of SREBP-1, thereby
      SIRT1 knockdown cells were more sensitive to MPA compared with progestin
      resistant cells. CONCLUSION: SIRT1/FoxO1/SREBP-1 act as a pathway targeting PR
      and involve in the development of progestin resistance in Ishikawa cells.

PMID- 30206736
TI  - The effects of tocolysis on neonatal septic death in women with PPROM: a
      retrospective cohort study.
AB  - PURPOSE: In women with preterm premature rupture of membranes (PPROM),
      particularly those with suspected chorioamnionitis, the benefit of tocolysis on
      neonatal outcome remains unclear. Our purpose was to evaluate the effect of
      tocolysis on neonatal septic death in women with PPROM with and without
      chorioamnionitis. METHODS: A retrospective cohort study was used to address our
      study objective. We created a cohort consisting of all live births between 24 and
      32 weeks' gestation that were registered in the Linked Birth and Infant Death
      data files (2009-2013) from the United States. Multivariate logistic regression
      was used to evaluate the effect of tocolysis on neonatal septic death at 7 and 28
      days in births with and without chorioamnionitis. RESULTS: Of the 46,968 births
      that met our inclusion criteria, tocolysis was administered to 6264 (13.3%).
      Tocolysis was more commonly prescribed to Caucasians, smokers, in multiple birth
      pregnancies, and to women with a history of preterm births. Tocolysis was not
      significantly associated with neonatal septic death at 7 days (OR 0.66, 95% CI
      0.39-1.13) or at 28 days (OR 0.85, 95% CI 0.60-1.19). This was consistent in
      pregnancies with and without chorioamnionitis. Furthermore, tocolysis was
      associated with a reduced risk of neonatal septic death at 7 days when
      administered between 24 and 27 weeks' gestation (OR 0.44, 95% CI 0.22-0.88).
      CONCLUSIONS: In the setting of PPROM, tocolysis does not appear to increase the
      risk of neonatal septic death at 7 and 28 days. Therefore, consideration should
      be given to its administration if clinically indicated.

PMID- 30206733
TI  - Ensembles of change-point detectors: implications for real-time BMI applications.
AB  - Brain-machine interfaces (BMIs) have been widely used to study basic and
      translational neuroscience questions. In real-time closed-loop neuroscience
      experiments, many practical issues arise, such as trial-by-trial variability, and
      spike sorting noise or multi-unit activity. In this paper, we propose a new
      framework for change-point detection based on ensembles of independent detectors
      in the context of BMI application for detecting acute pain signals. Motivated
      from ensemble learning, our proposed "ensembles of change-point detectors"
      (ECPDs) integrate multiple decisions from independent detectors, which may be
      derived based on data recorded from different trials, data recorded from
      different brain regions, data of different modalities, or models derived from
      different learning methods. By integrating multiple sources of information, the
      ECPDs aim to improve detection accuracy (in terms of true positive and true
      negative rates) and achieve an optimal trade-off of sensitivity and specificity.
      We validate our method using computer simulations and experimental recordings
      from freely behaving rats. Our results have shown superior and robust performance
      of ECPDS in detecting the onset of acute pain signals based on neuronal
      population spike activity (or combined with local field potentials) recorded from
      single or multiple brain regions.

PMID- 30206740
TI  - Blinded evaluation of cathepsin S inhibitors from the D3RGC3 dataset using
      molecular docking and free energy calculations.
AB  - During the last few years, we have developed a docking protocol involving two
      steps: (i) the choice of the most appropriate docking software and parameters for
      the system of interest using structural and functional information available in
      public databases (PDB, ChEMBL, PubChem Assay, BindingDB, etc.); (ii) the docking
      of ligand dataset to provide a prediction for the binding modes and ranking of
      ligands. We applied this protocol to the D3R Grand Challenge 3 dataset containing
      cathepsin S (CatS) inhibitors. Considering the size and conformational
      flexibility of ligands, the docking calculations afforded reasonable overall pose
      predictions, which are however dependent on the specific nature of each ligand.
      As expected, the correct ranking of docking poses is still challenging. Post
      processing of docking poses with molecular dynamics simulations in explicit
      solvent provided a significantly better prediction, whereas free energy
      calculations on a subset of compounds brought no significant improvement in the
      ranking prediction compared with the direct ranking obtained from the scoring
      function.

PMID- 30206730
TI  - Fluid Management in Acute Brain Injury.
AB  - PURPOSE OF THE REVIEW: The aims of fluid management in acute brain injury are to
      preserve or restore physiology and guarantee appropriate tissue perfusion,
      avoiding potential iatrogenic effects. We reviewed the literature, focusing on
      the clinical implications of the selected papers. Our purposes were to summarize
      the principles regulating the distribution of water between the intracellular,
      interstitial, and plasma compartments in the normal and the injured brain, and to
      clarify how these principles could guide fluid administration, with special
      reference to intracranial pressure control. RECENT FINDINGS: Although a
      considerable amount of research has been published on this topic and in general
      on fluid management in acute illness, the quality of the evidence tends to vary.
      Intravascular volume management should aim for euvolemia. There is evidence of
      harm with aggressive administration of fluid aimed at achieving hypervolemia in
      cases of subarachnoid hemorrhage. Isotonic crystalloids should be the preferred
      agents for volume replacement, while colloids, glucose-containing hypotonic
      solutions, and other hypotonic solutions or albumin should be avoided.
      Osmotherapy seems to be effective in intracranial hypertension management;
      however, there is no clear evidence regarding the superiority of hypertonic
      saline over mannitol. Fluid therapy plays an important role in the management of
      acute brain injury patients. However, fluids are a double-edged weapon because of
      the potential risk of hyper-hydration, hypo- or hyper-osmolar conditions, which
      may unfavorably affect the clinical course and the outcome.

PMID- 30206739
TI  - Zeolite X from coal fly ash inhibits proliferation of human breast cancer cell
      lines (MCF-7) via induction of S phase arrest and apoptosis.
AB  - In this study, zeolite X synthesised from coal fly ash (CFA) was examined for its
      anti-proliferative effects on human breast cancer MCF-7 cells by in vitro studies
      and allied probable molecular mechanism were also assessed. MTT assay exposed
      that zeolite X showed a concentration-dependent inhibitory result on the
      proliferation of MCF-7 cells and caused early apoptotic death and does not induce
      cytotoxicity in non-cancerous cells (MCF-12A). Flow cytometric study specified
      the accrual of cells at S phase suggest induction of apoptosis which was avowed
      through fluorescence and confocal microscopy following annexin V-FITC/propidium
      iodide (PI). MCF-7 cells treated by 10, 15 and 20 ug/ml concentrations of zeolite
      X showed internucleosomal DNA fragments in ladder form, thereby indicates cell
      death is associated with apoptosis. Mechanistically, our data support the
      induction of apoptosis through the activation of mitochondrial dependent pathway
      as indicated by an up-regulation of Bax and downregulation of Bcl-2 ratio, the
      expulsion of cytochrome c from the mitochondria to the cytosol and cleavage of
      pro-caspase-3 into activation of caspase-3 in MCF-7 cells. Based on these
      outcomes zeolite X induced early apoptosis and strongly provided experimental
      evidence for the usage of zeolite X as an essential therapeutic agent in the
      prevention and therapy of human breast cancer.

PMID- 30206741
TI  - Stability analysis of the antibiotic cocktail used by Treviso Tissue Bank
      Foundation for tissues decontamination.
AB  - Although careful donor selection reduces tissue contamination, close
      microbiological control of harvested allografts remains a key task of tissue
      banks. To guarantee the safety of human tissues for allograft transplantation, a
      decontamination regimen must be adopted which, as recommended by European
      guidelines, is active against the majority of microorganisms isolated in tissues.
      Antibiotic decontamination methods differ from one tissue bank to another in
      terms of antimicrobial agents, temperature and length of exposure. After
      identifying the most effective antibiotics against the bacterial strains most
      commonly isolated in allografts, Treviso Tissue Bank Foundation demonstrated the
      efficacy of an antibiotic cocktail for tissue decontamination containing
      Gentamicin, Vancomycin and Meropenem. The aim of this study was to analyse the
      degradation kinetics of the three antibiotics according to preparation method and
      use. The results show that only Meropenem is unstable at + 4  degrees C, while
      Gentamicin and Vancomycin are valid for over 10 days. We thus established to add
      Meropenem before the start of the tissue decontamination phase.

PMID- 30206742
TI  - [Validation of the Geriatric Check in a cohort of hospitalized neurological
      patients].
AB  - BACKGROUND: The Geriatrie-Check was developed as a screening tool for the
      identification of older patients with geriatric treatment requirements in
      hospitals. It was recommended by the Baden-Wuerttemberg Hospitals Association for
      routine use in hospitals in 2014 although no published validation studies are
      available. The test takes 3-5 min. AIM: Validation of the Geriatrie-Check in a
      prospective cohort of hospitalized neurological patients with and without
      geriatric characteristics. METHODS: In this prospective cross-sectional
      observational study at the University Hospital Tubingen, Germany the Geriatrie
      Check was compared with a comprehensive geriatric assessment in 107 neurological
      inpatients aged 70 years and older (41% women, mean age 76.7 years). RESULTS: The
      Geriatrie-Check classified 61 patients (57%) as geriatric patients. These
      patients with a positive result in the Geriatrie-Check had a higher percentage of
      frailty (according to Fried et al.), higher values in the Gerontopole frailty
      screening tool, higher values in the geriatric screening according to Lachs et
      el., slower gait speed, lower grip force, needed longer for the timed up-and-go
      test, had a greater fear of falling in the Falls Efficacy Scale - International,
      lower scores in the Mini Mental State Examination, needed more time to perform
      the Trail Making Test A and B, had higher values in the Beck's Depressions
      Inventar II and lower values in the visual analogue scale of the EQ-5D. A higher
      percentage of patients took more than five different drugs. INTERPRETATION AND
      CONCLUSION: The Geriatrie-Check has been shown to be a useful and valid tool for
      the identification of geriatric inpatients in neurological wards due to the good
      agreement with the results of the geriatric assessment.

PMID- 30206743
TI  - [Compatibility of occupation with nursing relatives in small and medium-sized
      businesses : Results of an explorative study in a "rural urban" center in eastern
      Lower Saxony].
AB  - In view of the increasing duties of employees as caregivers for relatives,
      questions arise concerning the compatibility of work and caregiving in the
      context of small and medium-sized enterprises. The aim of this exploratory study
      was to give first insights into this issue whereby the related perceptions and
      needs of this group were investigated. The research included semi-structured
      interviews with company executives and two workshops with employees according to
      the photovoice method. The results showed that the enterprises preferred informal
      in contrast to formal arrangements. Also, they did not have any knowledge
      concerning the care-related needs of their employees. The chief executive
      officers showed a highly superficial awareness of this problem. On the employees
      side the organizational efforts to maintain the care arrangement at home were
      articulated as a main issue, which could be supported by flexible working time
      regulations; however, in the current practice this was granted by the employers
      at the expense of their employees.

PMID- 30206737
TI  - Clinical Trials for Ductal Carcinoma In Situ of the Breast.
AB  - Ductal carcinoma in situ (DCIS) of the breast is a non-obligatory precursor to
      invasive breast carcinoma, with a variable natural history and biological
      potential for progression to invasive disease. Over the past 30 years, clinical
      trials have applied the therapeutic principles used for invasive carcinoma to
      treat DCIS (surgery, with or without breast radiotherapy, and post-operative
      endocrine therapy), with excellent survival outcomes, and in-breast recurrence
      rates that range from 0.5 to 1% annually. However, half of such recurrences are
      again in-situ lesions, and intensive therapy is likely not necessary for all
      patients. Current clinical research is focused on a better characterization of
      the potential of individual lesions to progress to invasive disease, and to
      identify women who would do well with lesser treatment. Three ongoing trials in
      the United States and Europe randomize women to active surveillance (with or
      without endocrine therapy) versus usual treatment with surgery and radiotherapy.
      The use of pre-operative endocrine therapy has been evaluated in a recently
      completed trial of letrozole use in postmenopausal women with DCIS; and in on
      going trials of tamoxifen, used either orally, or as a 4-hydroxytamoxifen gel
      formulation for application to the breast skin. This review summaries the major
      past and current clinical trials of DCIS, and the likely trajectories of DCIS
      management in the near future.

PMID- 30206732
TI  - A comprehensive catalogue of polyketide synthase gene clusters in lichenizing
      fungi.
AB  - Lichens are fungi that form symbiotic partnerships with algae. Although lichens
      produce diverse polyketides, difficulties in establishing and maintaining lichen
      cultures have prohibited detailed studies of their biosynthetic pathways.
      Creative, albeit non-definitive, methods have been developed to assign function
      to biosynthetic gene clusters in lieu of techniques such as gene knockout and
      heterologous expressions that are commonly applied to easily cultivatable
      organisms. We review a total of 81 completely sequenced polyketide synthase (PKS)
      genes from lichenizing fungi, comprising to our best efforts all complete and
      reported PKS genes in lichenizing fungi to date. This review provides an overview
      of the approaches used to locate and sequence PKS genes in lichen genomes,
      current approaches to assign function to lichen PKS gene clusters, and what
      polyketides are proposed to be biosynthesized by these PKS. We conclude with
      remarks on prospects for genomics-based natural products discovery in lichens. We
      hope that this review will serve as a guide to ongoing research efforts on
      polyketide biosynthesis in lichenizing fungi.

PMID- 30206744
TI  - [Physical training as core component of multimodal treatment of older frail
      people-study protocol of a randomized controlled pilot study].
AB  - BACKGROUND AND OBJECTIVE: Clinical practice guidelines recommend a multimodal
      intervention based on standardized screening for the treatment of frailty, which
      includes physical exercise as the main component. This study protocol describes a
      planned randomized controlled pilot study to evaluate the feasibility of a main
      study and first assessment of the effects of a multimodal, resource-oriented
      intervention program on frailty in older people. METHODS AND ANALYSES: A total of
      50 community-dwelling older men and women with frailty, >=65 years of age, will
      be randomly allocated to the intervention or control group. The intervention
      group receives usual care and a multimodal intervention program. This program
      consists of a multidimensional screening, verbal counselling, written
      instructions on individual functional and health status, a home-based physical
      exercise program (high-intensity functional exercise program, HIFE), and support
      related to cognition, mood, risk of falling, medication, nutrition and self-care
      as required. The control group participants will receive usual care only. The
      feasibility will be assessed by indicators for processes, resources and
      management (practicability), as well as for acceptance, safety and possible
      effects of the intervention. The frailty index and secondary clinical endpoints
      will be assessed before and after the 3-month intervention, as well as after a 3
      month follow-up to estimate the effects. Data will be analyzed according to the
      intention-to-treat principle. ETHICS AND DISSEMINATION: Ethical approval was
      obtained from the Ethics Committee of the German Physiotherapy Association (ref.
      number: 2017-02). Outcomes will be disseminated in a peer-reviewed journal and at
      specialist conferences. TRIAL REGISTRATION NUMBER: German Clinical Trial
      Register: DRKS00011831.

PMID- 30206746
TI  - Psychological Distress, Alexithymia and Alcohol Misuse in Patients with
      Psoriasis: A Cross-Sectional Study.
AB  - This study investigates (a) the prevalence of psychological distress, alexithymia
      and alcohol misuse in psoriasis patients; and (b) the relationship between
      psoriasis severity, alexithymia, alcohol and psychological distress in patients
      with psoriasis. A cross-sectional study was conducted. Outpatients (n = 184) with
      moderate to severe psoriasis completed a psychological screening battery.
      Measures included the Hospital Anxiety and Depression Scale, the Penn State Worry
      Questionnaire, the twenty-item Toronto Alexithymia Scale, the Dermatology Life
      Quality Index, the Psoriasis Area and Severity Index, the Self-Administered
      Psoriasis Area and Severity Index, and the Alcohol Use Disorders Identification
      Test. Demographic, clinical details and information on knowledge of psychosocial
      issues, alcohol and confidence on coping with distress and talking to others
      about psoriasis was also gathered. Alexithymia was associated with anxiety,
      depression and worry; subjective psoriasis severity was associated with worry.
      Alcohol misuse was related to anxiety and worry, but not to depression.
      Appropriate identification and treatment of alcohol difficulties and
      psychological distress of patients with psoriasis is needed.

PMID- 30206745
TI  - A novel noise filtered and occlusion removal: navigational accuracy in augmented
      reality-based constructive jaw surgery.
AB  - PURPOSE: Augmented reality-based constructive jaw surgery has been facing various
      limitations such as noise in real-time images, the navigational error of implants
      and jaw, image overlay error, and occlusion handling which have limited the
      implementation of augmented reality (AR) in corrective jaw surgery. This research
      aimed to improve the navigational accuracy, through noise and occlusion removal,
      during positioning of an implant in relation to the jaw bone to be cut or
      drilled. METHOD: The proposed system consists of a weighting-based de-noising
      filter and depth mapping-based occlusion removal for removing any occluded object
      such as surgical tools, the surgeon's body parts, and blood. RESULTS: The
      maxillary (upper jaw) and mandibular (lower jaw) jaw bone sample results show
      that the proposed method can achieve the image overlay error (video accuracy) of
      0.23~0.35 mm and processing time of 8-12 frames per second compared to 0.35~0.45
      mm and 6-11 frames per second by the existing best system. CONCLUSION: The
      proposed system concentrates on removing the noise from the real-time video frame
      and the occlusion. Thus, the acceptable range of accuracy and the processing time
      are provided by this study for surgeons for carrying out a smooth surgical flow.

PMID- 30206747
TI  - Cognitive Predictors of Parental Rescue Behavior and Malleability of Behavior
      Using a Brief Psychoeducation Intervention.
AB  - Cognitive factors, such as beliefs that anxiety is harmful, may lead parents to
      engage excessively in over-controlling parenting practices, such as "rescuing"
      children from distress. The present study examined whether parental rescue
      behavior, or the speed at which parents intervened to rescue an increasingly
      distressed child during an audio paradigm, was associated with beliefs about
      child anxiety. We also evaluated the impact of psychoeducation on rescue behavior
      during the audio paradigm. A nonclinical sample of 310 parents was recruited from
      an online crowdsourcing platform. Findings support the hypothesis that parents'
      stronger beliefs that anxiety is harmful relate to parents' faster speed of
      rescue. Additionally, participants who received psychoeducation delayed their
      rescue responses more than did participants who received benign information.
      Findings add to the growing body of evidence that cognitive factors contribute to
      countertherapeutic parent behavior and indicate that psychoeducation can be an
      important component of family-based child anxiety treatment.

PMID- 30206749
TI  - Correction to: Posttraumatic Stress Disorder Disturbs Coronary Tone and Its
      Regulatory Mechanisms.
AB  - The original version of this article unfortunately contained a mistake in the co
      author name.

PMID- 30206750
TI  - A Systematic Review of Family Victimization Experiences Among Sexual Minority
      Youth.
AB  - Sexual minority youth experience substantially higher rates of family
      victimization than their heterosexual peers. No systematic review has yet
      identified the predictors and consequences in this vulnerable population of
      childhood abuse, exposure to sibling abuse and domestic violence, and sibling
      aggression. This systematic review aims to (a) describe differences in these
      family victimization rates by sexual orientation, gender, and race/ethnicity; (b)
      identify potential sexual minority and non-sexual minority-specific risk factors;
      and (c) identify physical, mental, and behavioral health and extrafamilial
      victimization correlates. The systematic review, which followed PRISMA
      guidelines, yielded 32 articles that met study inclusion criteria. Rates of
      childhood physical, sexual, and emotional abuse were consistently higher for
      sexual minority youth than for their heterosexual peers. Bisexual youth appear to
      be at greater risk for physical abuse than their gay and lesbian peers. Younger
      age at sexual minority milestones (first awareness, disclosure, and same-sex
      sexual contact) and higher levels of sexual minority-specific (sexuality
      disclosure, gender non-conformity) and non-sexual minority-specific (delinquent
      behaviors, parental drinking) risk factors were associated with higher rates of
      family victimization. Sexual minorities who experienced some form of childhood
      abuse reported more frequent physical (higher rates of HIV, higher BMIs, lower
      levels of perceived health), mental (higher rates of depression, PTSD symptoms,
      experiential avoidance, internalized homophobia), and behavioral (higher rates of
      suicidality, substance misuse, earlier sexual debut, unprotected anal sex) health
      problems relative to heterosexual or non-abused sexual minority peers. Sexual
      minority females who experienced childhood physical or sexual abuse were at
      greater risk than abused sexual minority males for sexual assault later in life.
      We conclude this systematic review with recommendations for future research,
      including the necessity for longitudinal research that utilizes a poly
      victimization conceptual framework to identify the developmental pathways
      connecting risk factors, different types of family victimization, and health and
      extrafamilial victimization consequences.

PMID- 30206751
TI  - Mechanisms of karyotype evolution in the Brazilian scorpions of the subfamily
      Centruroidinae (Buthidae).
AB  - The recently-revised subfamily Centruroidinae is part of the New World clade of
      buthid scorpions. In this study, we analyzed the cytogenetic characteristics of
      nine of the 10 Brazilian centruroidines, and one undescribed species of the genus
      Ischnotelson, using a phylogenetic approach to determine the chromosomal
      rearrangements responsible for the differentiation of karyotypes among the
      species. The cytogenetic data recorded in the present study supported the new
      taxonomic arrangement of the Centruroidinae, with all the species of the same
      genus sharing the same or similar diploid numbers, i.e., 2n = 20 or 22 in
      Troglorhopalurus lacrau and T. translucidus, 2n = 25 or 26 in Ischnotelson sp.,
      I. guanambiensis and I. peruassu, and 2n = 28 in Jaguajir agamemnon, J. pintoi
      and J. rochae. The karyotype modelling in the ChromEvol software indicated 2n =
      18 as the ancestral diploid number of the Centruroidinae. The differentiation of
      karyotypes among the centruroidine genera was based on increasing chromosome
      numbers resulting from progressive fission events. These changes probably
      occurred prior to the diversification of the genera Ischnotelson, Jaguajir,
      Physoctonus and Rhopalurus, and appear to have played a more important role in
      karyotype evolution at the intergeneric level than the interspecific one.
      However, the observed increase in diploid numbers was not accompanied by changes
      in the number or location of ribosomal genes or telomeric sequences. The
      identification of meiotic cells in female specimens also allowed us to discuss
      the mechanisms of achiasmatic meiosis in scorpions.

PMID- 30206748
TI  - Paternal factors contributing to embryo quality.
AB  - PURPOSE: Advancing maternal and paternal age leads to a decrease in fertility,
      and hence, many infertile couples opt for assisted reproductive technologies
      [ART] to achieve biological parenthood. One of the key determinants of achieving
      a live outcome of ART, embryo quality, depends on both the quality of the oocyte
      and sperm that have created the embryo. Several studies have explored the effect
      of oocyte parameters on embryo quality, but the effects of sperm quality on the
      embryo have not been comprehensively evaluated. METHOD: In this review, we assess
      the effect of various genetic factors of paternal origin on the quality and
      development of the embryo. RESULTS: The effects of sperm aneuploidy, sperm
      chromatin structure, deoxyribonucleic acid [DNA] fragmentation, role of
      protamines and histones, sperm epigenetic profile, and Y chromosome
      microdeletions were explored and found to negatively affect embryo quality.
      CONCLUSION: We propose that careful assessment of spermatozoal parameters is
      essential to achieve embryo development and a healthy live birth. However, the
      heterogeneity in test results and the different approaches of assessing a single
      sperm parameter highlight the need for more research and the development of
      standardized protocols to assess the role of sperm factors affecting embryo
      quality.

PMID- 30206753
TI  - Effect of transplant status in CD19-targeted CAR T-cell therapy: a systematic
      review and meta-analysis.
AB  - Chimeric antigen receptor (CAR) T-cell therapy has shown promise for
      relapsed/refractory malignancies. Many patients have undergone prior
      hematopoietic stem cell transplant (HSCT), yet effects of transplant status on
      CAR T-cell therapy efficacy and safety have not been reported. The purpose of the
      study is to systematically evaluate the likelihood of achieving optimum response,
      severe cytokine release syndrome (sCRS), and neurotoxicity in the context of CAR
      T-cell therapy for HSCT-naive patients versus those with prior HSCT. Trials were
      identified in ClinicalTrials.gov, Cochrane Library, and PubMed, and through
      reference pearl growing. Included studies used CD19-directed CAR T-cells for
      relapsed/refractory B-lineage Acute Lymphoblastic Leukemia and B cell Chronic
      Lymphocytic Leukemia, enrolled both HSCT-naive and prior-HSCT patients, and
      denoted transplant status with outcomes. Six studies were included for optimum
      response, five for sCRS incidence, and four for neurotoxicity incidence. The
      pooled odds ratio for optimum response was 1.57 favoring HSCT-naive patients (95%
      CI 0.54-4.61), whereas the pooled odds ratios for sCRS and neurotoxicity were
      1.41 (95% CI 0.51-3.94) and 1.37 (95% CI 0.28-6.77), respectively, toward HSCT
      naive patients. Odds ratios were non-statistically significant. Overall risk of
      bias was moderate. While pooled estimates showed an advantage among HSCT-naive
      patients for achieving optimum response and increased likelihood for sCRS and
      neurotoxicity, findings were not statistically significant. Any differences in
      efficacy and safety of CAR T-cell therapy cannot be verifiably attributed to
      transplant status, and additional controlled trials with increased sample sizes
      are needed to determine whether suggestive patterns favoring HSCT-naive patients
      are validated.

PMID- 30206754
TI  - Lead contamination of the mining and smelting district in Mitrovica, Kosovo.
AB  - Lead contamination in topsoil of the mining and smelting area of Mitrovica,
      Kosovo, was investigated for total concentrations and chemical fractions by
      sequential extraction analysis, mineralogical fractions by X-ray diffraction
      (XRD) and scanning electron microscopy with energy-dispersive X-ray spectrometer
      (SEM-EDX). The study revealed that all samples contained Pb exceeding USEPA
      standard of 400 mg kg-1. The highest total concentration of Pb (125,000 mg kg-1)
      was the soil from the former smelter. Sequential extraction results showed that
      the predominant form of Pb was associated with Fe-Mn oxide-bound fraction which
      ranged from 45.37 to 71.61% of total concentrations, while carbonate and silicate
      Pb-binding fractions were dominant when physical measurements (XRD and SEM-EDX)
      were applied. Application of Pb isotope ratios (206Pb/207Pb and 208Pb/206Pb),
      measured by inductively coupled plasma mass spectrometry, identified that Pb
      contamination is originated from similar anthropogenic source. The results
      reflected that the Pb contamination in the soil of this area is serious. In order
      to provide proper approaches on remediation and prevention of health impacts to
      the people in this area, a continuous monitoring and health risk assessment are
      recommended.

PMID- 30206752
TI  - Cloning, characterization and function analysis of DAX1 in Chinese loach
      (Paramisgurnus dabryanus).
AB  - The mechanisms of sex determination and differentiation have not been elucidated
      in most fish species. In this study, the full-length cDNAs of DAX1 was cloned and
      characterized in aquaculture fish Chinese loach (Paramisgurnus dabryanus),
      designated as Pd-DAX1. The cDNA sequence of Pd-DAX1 was 1261 bp, including 795 bp
      open reading frame (ORF) encoding 264 amino acids. Pd-DAX1 shares highly
      identical sequence with DAX1 homologues from different species. The expression
      profiles of Pd-DAX1 in different developmental stages and diverse adult tissues
      were analyzed by quantitative real-time RT-PCR and in situ hybridization (ISH).
      Pd-DAX1 was continuously expressed during embryogenesis, with the extensive
      distribution in the development of the central nervous system. Tissue
      distribution analysis revealed that Pd-DAX1 expressed widely in adult tissues,
      with the highest expression level found in testis, moderate level in ovary,
      showing a sex-dimorphic expression pattern. Pd-DAX1 mainly located in
      spermatogonia cells, spermatocytes, primary oocytes and previtellogenic oocyte
      cells, implying that Pd-DAX1 may involve in gametogenesis. These preliminary
      findings suggest that Pd-DAX1 gene is highly conserved during vertebrate
      evolution and involved in a wide range of developmental processes including
      embryogenesis, central nervous system development and gonad development.

PMID- 30206755
TI  - A Systematic Review of Interventions to Minimize Transportation Barriers Among
      People with Chronic Diseases.
AB  - Transportation is an important social determinant of health. Transportation
      barriers disproportionately affect the most vulnerable groups of society who
      carry the highest burden of chronic diseases; therefore, it is critical to
      identify interventions that improve access to transportation. We synthesized
      evidence concerning the types and impact of interventions that address
      transportation to chronic care management. A systematic literature search of peer
      reviewed studies that include an intervention with a transportation component was
      performed using three electronic databases-PubMed, EMBASE, and CINAHL-along with
      a hand-search. We screened 478 unique titles and abstracts. Two reviewers
      independently evaluated 41 full-text articles and 10 studies met eligibility
      criteria for inclusion. The transportation interventions included one or more of
      the following: providing bus passes (n = 5), taxi/transport vouchers or
      reimbursement (n = 3), arranging or connecting participants to transportation (n
      = 2), and a free shuttle service (n = 1). Transportation support was offered
      within multi-component interventions including counseling, care coordination,
      education, financial incentives, motivational interviewing, and navigation
      assistance. Community health/outreach workers (n = 3), nurses (n = 3), and
      research or clinic staff (n = 3) were the most common interventionists. Studies
      reported improvements in cancer screening rates, chronic disease management,
      hospital utilization, linkage and follow up to care, and maternal empathy.
      Overall, transportation is a well-documented barrier to engaging in chronic care
      among vulnerable populations. We found evidence suggesting transportation
      services offered in combination with other tailored services improves patient
      health outcomes; however, future research is warranted to examine the separate
      impact of transportation interventions that are tested within multi-component
      studies.

PMID- 30206756
TI  - An Increased Chromosome 7 Copy Number in Endoscopic Bile Duct Biopsy Specimens Is
      Predictive of a Poor Prognosis in Cholangiocarcinoma.
AB  - BACKGROUND: The ability of fluorescence in situ hybridization (FISH) assays in
      endoscopic transpapillary bile duct biopsy specimens to predict the prognosis of
      cholangiocarcinoma (CCA) has not been elucidated. AIMS: We aimed to clarify the
      association between the results of UroVysion FISH assays and the prognosis of
      CCA. METHODS: We retrospectively reviewed 49 specimens obtained by transpapillary
      forceps biopsy from consecutive patients with CCA. The copy numbers of
      chromosomes 3, 7, and 17 were evaluated by FISH assay using UroVysion. We
      compared the overall survival (OS) of CCA patients with and without increased
      copy numbers of chromosomes 3, 7, and 17. Furthermore, we evaluated the
      association between OS and the clinicopathological parameters of CCA patients.
      RESULTS: The OS was significantly shorter in patients with than without an
      increased chromosome 7 copy number (log-rank p = 0.015; median OS 11.9 vs. 20.7
      months). In the univariate analyses, age (p = 0.012), ECOG performance status (p
      = 0.046), tumor stage (p = 0.046), surgery (p = 0.006), and an increased
      chromosome 7 copy number (p = 0.017) were significantly associated with OS. The
      multivariate analysis revealed that an increased chromosome 7 copy number (hazard
      ratio, 2.46; 95% CI 1.15-5.27; p = 0.021) and advanced clinical stage (hazard
      ratio, 2.26; 95% CI 1.11-4.63; p = 0.025) were independently predictive of a poor
      OS. CONCLUSIONS: Detection by FISH assay of an increased chromosome 7 copy number
      in transpapillary forceps biopsy specimens is predictive of a poor prognosis in
      CCA patients.

PMID- 30206757
TI  - Activation of PD-1 Protects Intestinal Immune Defense Through IL-10/miR-155
      Pathway After Intestinal Ischemia Reperfusion.
AB  - BACKGROUND: To date, mechanisms of intestinal immunoglobulin (Ig) dysfunction
      following intestinal ischemia/reperfusion (I/R) remain unclear. Programmed death
      1 (PD-1) is associated with immune responses of lymphocytes. AIM: We aimed to
      verify the hypothesis that activation of PD-1 may improve intestinal immune
      dysfunction by regulating IL-10/miR-155 production after intestinal IR injury.
      METHODS: Intestinal I/R injury was induced in mice by clamping the superior
      mesenteric artery for 1 h followed by 2-h reperfusion. PD-L1 fusion Ig, anti
      interleukin (IL)-10 monoclonal antibody (mAb), and microRNA (miR)-155 agomir were
      administered. PD-1 expression, IL-10 mRNA, and protein expression in Peyer's
      patches (PP) CD4+ cells were measured. MiR-155 levels, tumor necrosis factor
      (TNF)-alpha and IL-1beta concentration, and activation-induced cytidine deaminase
      (AID), a key enzyme for intestinal immune antibodies, in PP tissues were
      measured, respectively. Importantly, the production and cecal bacteria-binding
      capacity of IgA and IgM were detected. RESULTS: Intestinal I/R led to decreased
      PD-1 expression, imbalanced production, and impaired bacteria-binding capacity of
      IgA and IgM. Activating PD-1 by PD-L1 Ig facilitated IL-10 synthesis, then
      decreased miR-155 levels, and subsequently promoted AID expression and reduced
      TNF-alpha, IL-1beta concentration. Upregulation of AID improved the disruptions
      of intestinal immune barrier caused by IgA and IgM dysfunction. Anti-IL-10 mAb
      and miR-155 agomir abolished the protective effects of PD-L1 Ig on the intestinal
      immune defense. CONCLUSION: Activation of PD-1 with PD-L1 Ig relieves intestinal
      immune defensive injury through IL-10/miR-155 pathway following intestinal I/R
      attack. PD-1, IL-10, and miR-155 may be potential targets for the damages of
      intestinal barrier and immunity.

PMID- 30206758
TI  - Spirituality in medical education: a concept analysis.
AB  - Spirituality in medical education is an abstract multifaceted concept, related to
      the healthcare system. As a significant dimension of health, the importance and
      promotion of this concept has received considerable attention all over the world.
      However, it is still an abstract concept and its use in different contexts leads
      to different perceptions, thereby causing challenges. In this regard, the study
      aimed to clarify the existing ambiguities of the concept of spirituality in
      medical education. Walker and Avant (Strategies for theory construction in
      nursing, Prentice Hall, Boston, 2011) concept analysis eight-step approach was
      used. After an extensive review of online national and international databases
      from 2000 to 2015, 180 articles and 3 books in English and Persian were retrieved
      for the purposes of the study. Analysis revealed that the defining attributes of
      spirituality in medical education are: teaching with all heart and soul, Life
      inspiring, ontological multidimensional connectedness, religious-secular
      spectrum, and socio-cultural intricacies. Moreover, innate wisdom, skillful
      treatment, transcendent education, and environmental requirements were
      antecedents to this concept, with the health of body and soul, intrapersonal
      development and elevation, and responsive treatment and education being its
      consequences. The defining attributes provided in this study can assist
      physicians, instructors, and professors to develop and implement evidence-based,
      health based and comprehensive education plans according to the guidelines of
      professional ethics and qualification of using spirituality in practice. The
      clarification of the noted concept facilitates further development of medical
      knowledge, research, and research instruments.

PMID- 30206759
TI  - Advances in Asthma - III.

PMID- 30206760
TI  - Hepatitis A Virus, Hepatitis E Virus, and Rotavirus in Foods of Animal Origin
      Traded at the Borders of Brazil, Argentina, and Uruguay.
AB  - The aim of this study was to investigate hepatitis A virus (HAV), hepatitis E
      (HEV), and rotavirus (RV) in fresh and processed meat traded on the border of
      Brazil with Argentina and Uruguay. In total, 159 samples of raw and processed
      foods of animal origin were collected in Paso de los Libres, Argentina (n = 53
      raw meat, n = 24 processed meat) and Rivera, Uruguay (n = 55 raw meat, n = 18
      processed meat), or were seized by the Brazilian International Agricultural
      Surveillance System-VIGIAGRO (Brazil-Argentina border) (n = 8 raw meat, n = 1
      bush meat). All samples were tested for the presence of HAV, HEV, and RV genomes.
      HAV genes were detected in 18.23% of samples and RV genes in 23.89%. No HEV
      positive samples were detected. HAV was also detected in two of the VIGIAGRO
      samples. Processed meats from Argentina and Uruguay had a higher rate of HAV and
      RV than raw meat (P > 0.05). The median HAV in the Argentinian and Uruguayan
      samples was 6.9 * 104 and 3.5 * 103 copies/g, respectively. The presence of RV
      viral genes in raw meats from Argentina was significant, and this was not
      observed in processed meats. The presence of HAV and RV genes in a significant
      portion of products from Argentina and Uruguay is a potential source of human
      infection. This also indicates precarious conditions of acquisition, processing,
      and manipulation, which could be improved by improved regulation of food across
      borders.

PMID- 30206761
TI  - Metabolic effects of reduced growth hormone action in fatty liver disease.
AB  - BACKGROUND: Adult growth hormone (GH) deficiency is associated with fatty liver
      disease and shows several features of the metabolic syndrome. Vice versa obesity
      is characterized as a state of low GH function. Here, we aimed to define the role
      of hepatic GH signaling and its metabolic consequences in non-alcoholic fatty
      liver disease. METHODS: In humans, GHR and IGF-1 levels were determined in liver
      samples of 29 obese patients with non-alcoholic steatohepatitis (NASH) or simple
      steatosis. Cellular effects of GH on insulin signaling were investigated in GH
      receptor (GHR) knockdown HepG2 cells. RESULTS: Hepatic IGF-1 expression levels
      reflecting GH action were significantly lower and fasting glucose concentrations
      higher in patients with NASH than in patients with simple steatosis. GHR
      knockdown in hepatocytes resulted in a scenario of high glucose output displayed
      by reduced glycogen content, increased gluconeogenesis and diminished insulin
      signaling. CONCLUSIONS: Our data suggest that GH signaling in the liver is
      diminished in patients with NASH and associated with deteriorated hepatic insulin
      sensitivity and metabolic activity. Reduced hepatic GH action might contribute to
      insulin resistance in obese patients with NASH.

PMID- 30206762
TI  - Endoscopic drainage of obstructed biliary system in altered gastrointestinal
      anatomy: An experience from a tertiary center in India.
AB  - INTRODUCTION: With the advances in imaging and endoscopic technology, scope of
      endoscopic interventions in biliary obstruction associated with altered
      gastrointestinal (GI) anatomy has increased. We analyzed our experience on single
      balloon enteroscopy and endoscopic ultrasound (EUS)-guided ERCP (SBE-ERCP) and
      EUS-guided hepatogastrostomy (EUS-HG) in the presence of altered GI anatomy.
      METHODS: Data of 15 patients (SBE-ERCP in 12, and EUS-HG in 3) over a period of 1
      year (April 2016-March 2017) and followed up for 90 to 270 days were
      retrospectively analyzed. Inclusion criteria were (a) age 18-80 years, (b) fit
      for anesthesia, (c) intact primary confluence, (d) failed percutaneous
      transhepatic biliary drainage (PTBD) or difficult EUS-HG (due to poor
      visualization of intrahepatic ducts due to pneumobilia after PTBD; SBE-ERCP was
      undertaken in them), and (e) cholangitis without shock. Exclusion criteria were
      (a) involved or separated primary biliary confluence, (b) shock, (c) unfit for
      anesthesia, and (d) liver metastasis in the left lobe (EUS-HG). RESULTS: All were
      symptomatic with pain, jaundice, and cholangitis. The median serum bilirubin and
      serum alkaline phosphatase (SAP) were 2.8 mg/dL and 273 IU/mL, respectively. SBE
      ERCP in 12 and EUS-HG in 3 cases were  done successfully with observed success
      rate of 91.6% and 100% (3/3), respectively. Three patients had minor
      complications (post-procedure pain, fever, and pneumoperitoneum), which were
      managed conservatively. CONCLUSION: Endoscopic interventions in patients with
      altered GI anatomy are safe.

PMID- 30206763
TI  - The prognostic value of maximal surgical resection is attenuated in
      oligodendroglioma subgroups of adult diffuse glioma: a multicenter retrospective
      study.
AB  - PURPOSE: Maximal surgical resection is associated with survival benefit in the
      majority of studies in adult diffuse glioma. This study aims to characterize the
      prognostic value of surgical resection in molecular subgroups of diffuse glioma.
      METHODS: 1178 patients with diffuse glioma from our centers and 422 from TCGA
      dataset were collected. The Kaplan-Meier analysis and multivariable Cox
      regression models were conducted to identify the prognostic value of surgical
      resection through different histological and molecular stratifications. RESULTS:
      Firstly, we confirmed progression-free survival (PFS) benefit associated with
      gross total resection (GTR) over sub-total resection (STR) in lower-grade glioma
      (HR 1.49; 95% CI 1.17-1.90; P = 0.001). Intriguingly however, we were unable to
      detect a significant PFS or overall survival (OS) benefit in oligodendroglioma (N
      = 397; HR 1.36; 95% CI 0.86-2.14; P = 0.19 and HR 1.05; 95% CI 0.55-1.99; P =
      0.89, respectively). Secondly, when analyzed in molecular subgroups, we were
      similarly unable to detect a significant PFS or OS benefit in IDH MT/codel
      subgroup (N = 269; HR 1.47; 95% CI 0.92-2.34; P = 0.11 and HR 1.54; 95% CI 0.78
      3.05; P = 0.21, respectively), oligodendroglioma with IDH MT/codel subgroup (N =
      233; HR 1.33; 95% CI 0.79-2.21; P = 0.28 and HR 1.16; 95% CI 0.53-2.54; P = 0.70,
      respectively) or other relevant subgroups. TCGA validation also showed a
      significant survival benefit in astrocytoma rather than oligodendroglioma.
      Exploratory RNAseq analysis displayed that fewer cell proliferation-related gene
      expression features were specific to oligodendroglioma. CONCLUSION: These results
      suggest that the benefit of maximal surgery may be attenuated in patients within
      oligodendroglioma relevant subgroups because of the chemosensitive and indolent
      nature. The aggressive surgery accompanying with risk of neurologic morbidity may
      be unnecessary for these patients given the lack of survival benefit with gross
      total resection.

PMID- 30206764
TI  - Reirradiation and PD-1 inhibition with nivolumab for the treatment of recurrent
      diffuse intrinsic pontine glioma: a single-institution experience.
AB  - BACKGROUND: Diffuse intrinsic pontine glioma (DIPG) is a rare, aggressive brain
      tumor with no known cure. Reirradiation (reRT) at recurrence can prolong
      survival. The impact of irradiation may be heightened when combined with PD-1
      inhibition. We describe our experience using reRT, with or without PD-1
      inhibition, in a cohort of patients with recurrent DIPG. METHODS: We performed a
      retrospective cohort analysis of children who received reRT with or without
      concomitant PD-1 inhibition for recurrent DIPG at a single institution between
      2005 and 2016. We compared progression-free (PFS) and overall survival (OS)
      between those who received reRT alone or in combination with PD-1 inhibition. We
      then compared reRT to a cohort of patients who did not receive reRT. RESULTS:
      Thirty-one patients were included (8-reRT with nivolumab; 4-reRT alone; 19-no
      reRT). Patients who received reRT had prolonged OS compared to no reRT (22.9
      months-reRT with nivolumab; 20.4 months-reRT alone; 8.3 months-no reRT; p <
      0.0001). Patients who received reRT with nivolumab vs. reRT only had slightly
      prolonged OS from diagnosis and from reRT (22.9 vs. 20.4 months for time from
      diagnosis; 6.8 vs. 6.0 months for time from reRT). All patients receiving reRT
      with or without nivolumab tolerated the therapy without acute or late toxicity.
      CONCLUSIONS: Our experience demonstrates the tolerability of reRT with concurrent
      PD-1 inhibition for recurrent DIPG and suggests that combination therapy may
      offer survival benefit. Future prospective studies are needed to confirm the
      benefits of this combination therapy.

PMID- 30206765
TI  - Concomitant PPARalpha and FXR Activation as a Putative Mechanism of NASH
      Improvement after Gastric Bypass Surgery: a GEO Datasets Analysis.
AB  - BACKGROUND: Compared to non-surgical weight loss (Diet), weight loss after Roux
      en-Y gastric bypass (RYGB) results in greater rates of non-alcoholic
      steatohepatitis (NASH) resolution. Changes in bile acid physiology and farnesoid
      X receptor (FXR) signaling are suspected mediators of postoperative NASH
      improvement. Recent experimental evidence suggests that upregulation of hepatic
      peroxisome proliferator-activated receptor alpha (PPARalpha) activity might also
      impact NASH improvement. As FXR partly regulates PPARalpha, we compared
      resolution of NASH and changes in hepatic PPARalpha and FXR gene expression
      following Diet and RYGB. METHODS: We searched the Gene Expression Omnibus
      database to identify human studies with liver biopsies containing genomic data
      and histologic NASH features, at baseline and after Diet or RYGB. Microarray data
      were extracted for PPARalpha and FXR gene expression analyses using GEOquery R
      package v.2.42.0. RESULTS: We identified one study (GSE83452) where patients
      underwent either Diet (n = 29) or RYGB (n = 25). NASH prevalence was similar at
      baseline (Diet 76% versus RYGB 60%, P = ns). After 1 year, NASH resolved in 93.3%
      of RYGB but only in 27.3% of Diet (P < 0.001). Hepatic PPARalpha and FXR gene
      expression increased only after RYGB (P < 0.001). These changes were also found
      when analyzing only patients that resolved NASH (P < 0.01), and patients without
      NASH at baseline and follow-up (P < 0.05). CONCLUSIONS: Compared to Diet, RYGB
      results in greater NASH resolution with concurrent upregulation of hepatic
      PPARalpha and FXR. Our findings point to concurrent PPARalpha and FXR activation,
      triggered by RYGB, as a potential mechanism to improve NASH.

PMID- 30206766
TI  - Enzymological characteristics of a novel archaeal dye-linked D-lactate
      dehydrogenase showing loose binding of FAD.
AB  - A gene-encoding a dye-linked D-lactate dehydrogenase (Dye-DLDH) homolog was
      identified in the genome of the hyperthermophilic archaeon Thermoproteus tenax.
      The gene was expressed in Escherichia coli and the product was purified to
      homogeneity. The recombinant protein exhibited highly thermostable Dye-DLDH
      activity. To date, four types of Dye-DLDH have been identified in
      hyperthermophilic archaea (in Aeropyrum pernix, Sulfolobus tokodaii,
      Archaeoglobus fulgidus, and Candidatus Caldiarchaeum subterraneum). The amino
      acid sequence of T. tenax Dye-DLDH showed the highest similarity (45%) to A.
      pernix Dye-DLDH, but neither contained a known FAD-binding motif. Nonetheless,
      both homologs required FAD for enzymatic activity, suggesting that FAD binds
      loosely to the enzyme and is easily released unlike in other Dye-DLDHs. Our
      findings indicate that Dye-DLDHs from T. tenax and A. pernix are a novel type of
      Dye-DLDH characterized by loose binding of FAD.

PMID- 30206767
TI  - Analysis of the motion of vacuolar volutin granules in Saccharomyces cerevisiae.
AB  - The moving volutin (polyphosphate) granules known as "dancing bodies" can be
      observed in the vacuoles of the yeast cells. The aim of work was to study the
      effects of cultivation conditions and influences of physico-chemical factors on
      the motion of vacuolar volutin granules in Saccharomyces cerevisiae cells. The
      motion of granules is a non-Markovian process. It does not depend on the cell
      cycle phase, but depends on the growth stage. The maximal number of cells with
      "dancing bodies" was observed under cultivation of yeast at 25-28  degrees C and
      pH 5.4-5.8. Irradiation by non-ionizing electromagnetic radiation (EMR) of
      extremely high frequency (61.22 GHz, 100 MUW, 30 min) had no effect on granule
      motion. After irradiation by non-ionizing EMR of very high frequency (40.68 MHz,
      30 W, 30 min) the number of cells with "dancing bodies" decreased significantly
      and in 2 h restored almost to the control value. The possible nature of the
      moving volutin granules phenomenon due to metabolic processes is discussed.

PMID- 30206768
TI  - Homoharringtonine synergy with oridonin in treatment of t(8; 21) acute myeloid
      leukemia.
AB  - Collaboration of c-KIT mutations with AML1-ETO (AE) has been demonstrated to
      induce t(8; 21) acute myeloid leukemia (AML). Targeted therapies designed to
      eliminate AE and c-KIT oncoproteins may facilitate effective treatment of t(8;
      21) AML. Homoharringtonine (HHT) features activity against tumor cells harboring
      c-KIT mutations, whereas oridonin can induce t(8; 21) AML cell apoptosis and AE
      cleavage. Therefore, studies should explore the efficacy of combination therapy
      with oridonin and HHT in t(8; 21) AML. In this study, we investigated the
      synergistic effects and mechanism of oridonin combined with HHT in t(8; 21) AML
      cell line and mouse model. The two drugs synergistically inhibited cell viability
      and induced significant mitochondrial membrane potential loss and apoptosis.
      Oridonin and HHT induced significant downregulation of c-KIT and its downstream
      signaling pathways and promoted AE cleavage. HHT increased intracellular oridonin
      concentration by modulating the expressions of MRP1 and MDR1, thus enhancing the
      effects of oridonin. The combination of oridonin and HHT prolonged t(8; 21)
      leukemia mouse survival. In conclusion, oridonin and HHTexert synergistic effects
      against t(8; 21) leukemia in vivo and in vitro, thereby indicating that their
      combination may be an effective therapy for t(8; 21) leukemia.

PMID- 30206769
TI  - Factors Associated with Access to Maternal and Reproductive Health Care among
      Somali Refugee Women Resettled in Ohio, United States: A Cross-Sectional Survey.
AB  - This study examined maternal and reproductive health (MRH) access of Somali
      refugees in the U.S. across four access dimensions (willingness to seek care,
      gaining entry to the health system, seeing a primary provider and seeing a
      specialist). We conducted a cross-sectional survey of 427 Somali refugee
      reproductive-age women in Franklin County, Ohio. Following descriptive statistics
      of demographics, we conducted multivariate analyses to test associations between
      demographics and the four access dimensions. Most Somali refugee women were
      married (68%), attained primary education (92%), employed (64%) and were
      circumcised (82%). Young (OR 2.61, 95% CI 1.25-5.60), single (OR 1.78, 95% CI
      1.15-2.78), and minors upon arrival (OR 2.36, 95% CI 1.44-3.90) were more willing
      to seek care. Lack of insurance, limited language fluency and being circumcised
      limited access to care across all dimensions. Barriers to access need to be
      systematically addressed. Deconstructing beliefs regarding health systems may
      improve access, especially among older Somali women.

PMID- 30206770
TI  - Neuregulin-1beta Plays a Neuroprotective Role by Inhibiting the Cdk5 Signaling
      Pathway after Cerebral Ischemia-Reperfusion Injury in Rats.
AB  - This study investigated the effects of neuregulin-1beta (NRG1beta) after middle
      cerebral artery occlusion/reperfusion (MCAO/R) in rats to evaluate whether they
      occur via the cyclin-dependent kinase (Cdk)5 signaling pathway. One hundred adult
      male Wistar rats were randomly divided into sham, MCAO/R, treatment (NRG1beta),
      inhibitor (roscovitine; Ros), and inhibitor + treatment (Ros + NRG1beta) groups.
      The MCAO/R model was established using the intraluminal thread method. The
      neurobehavioral function was evaluated by the modified neurological severity
      score (mNSS). The cerebral infarction volume (CIV) was measured by triphenyl
      tetrazolium chloride (TTC) staining. Morphological changes were observed by
      hematoxylin-eosin (HE) staining. The apoptotic cell index (ACI) was detected by
      the terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay.
      Immunohistochemistry and Western blotting were performed to detect the expression
      of calpain 1, p35/p25 (regulatory binding partners of Cdk5), Cdk5, and p-Tau in
      neurons. The neuronal morphology in the MCAO/R, NRG1beta, Ros + NRG1beta, and Ros
      groups differed compared to the sham group; the mNSS, CIV, ACI, and the
      expression of calpain 1, p35/p25, Cdk5, and p-Tau were significantly increased in
      all four groups (P < 0.05). In the NRG1beta, Ros and Ros + NRG1beta groups, the
      neuronal morphology was significantly improved compared to the MCAO/R group, as
      were the mNSS, CIV, and ACI. The levels of calpain 1, p35/p25, and p-Tau were
      decreased compared with the MCAO/R group (P < 0.05), while the Cdk5 expression
      was not significantly different (P > 0.05). NRG1beta may exert neuroprotective
      effects by inhibiting the expression of calpain 1, p35/p25, and p-Tau after
      cerebral ischemia-reperfusion injury.

PMID- 30206771
TI  - Impulse control disorders in patients with prolactinoma receiving dopamine
      agonist therapy: a prospective study with 1 year follow-up.
AB  - OBJECTIVE: To assess prospectively the prevalence of impulse control disorders
      (ICD), psychiatric symptoms, and their clinical correlates in patients with
      prolactinoma receiving dopamine agonists (DA) in comparison to those with non
      functioning pituitary adenomas (NFA) and healthy controls (HC). METHODS: A total
      of 25 patients with prolactinoma, 31 with NFA, and 32 HCs were included in the
      study. All patients and controls were screened for the presence of ICDs and other
      psychiatric disorders using revised version of Minnesota Impulsive Disorders
      Interview (MIDI-R), Barratt Impulsiveness Scale (BIS-11), Symptom Check List (SCL
      90-R) questionnaire and Beck Depression Inventory (BDI), and Beck Anxiety
      Inventory (BAI). RESULTS: We detected two new cases (8%) of ICD associated with
      DAs. Both cases presented with hypersexuality, which reversed totally or
      decreased upon discontinuation of the drug. The re-challenge of the DA in a
      smaller dose has led to either no symptoms or weaker symptoms than before. There
      was an increase in the number of patients who screened positive on obsession,
      interpersonal sensitivity, paranoid ideation, and additional items subscales of
      SCL-90-R in comparison to HCs at the end of the study period (p < 0.05 for all).
      Likewise, cumulative DA dose was positively correlated to obsession,
      interpersonal sensitivity, paranoid ideation, hostility, phobic anxiety
      subscales, and GSI scores of SCL-90-R (p < 0.05 for all). CONCLUSIONS: DAs are
      associated with a small but substantial short-term risk of ICD development and a
      broad range of psychiatric symptoms in patients with prolactinoma receiving DAs.

PMID- 30206773
TI  - The distribution of nerves supplying the testis, epididymis and accessory sex
      glands of Suncus murinus.
AB  - Chronic testicular pain remains an important challenge for urologists.
      Investigation of the innervation of male gonads thus becomes essential for
      deepening our understanding of their regulatory roles in male reproductive
      physiology and pathophysiology. Studies of testicular innervation are mainly
      limited to the intratesticular peptidergic nerves of the testis by
      immunohistochemical and acetylcholinesterase histochemical investigations in some
      animals. Little is known about the detailed, overall distribution in general
      experimental animal testis. In this study, the distribution of nerves supplying
      the testis, epididymis and accessory sex glands of Suncus murinus was
      investigated by whole mount immunohistochemistry staining using a neurofilament
      protein antibody. Testicular nerves arose through three routes: nerves deriving
      from the mesenteric and renal plexuses accompanied the testicular artery,
      entering into the testicular hilum through the superior ligament of the testis.
      The nerves originating from the hypogastric plexus then ran along the internal
      iliac artery, deferential artery, and passed through the mesoductus deferens or
      mesoepididymis, innervating the cauda and corpus of the epididymis, the vas
      deferens and the inferior pole of the testis. The third route arose from the
      pelvic plexus, distributed in the seminal vesicle and the prostate. The density
      of nerve fibers was higher in the cauda epididymidis than in the testis, and more
      abundant in the vas deferens. The different origins and distribution densities of
      testicular nerves in S. murinus may serve different neuronal regulatory
      functions, and, therefore, S. murinus may be an important model animal for
      understanding the different characteristics of testicular pain.

PMID- 30206772
TI  - Volumetric and texture analysis of pretherapeutic 18F-FDG PET can predict overall
      survival in medullary thyroid cancer patients treated with Vandetanib.
AB  - PURPOSE: The metabolically most active lesion in 2-deoxy-2-(18F)fluoro-D-glucose
      (18F-FDG) PET/CT can predict progression-free survival (PFS) in patients with
      medullary thyroid carcinoma (MTC) starting treatment with the tyrosine kinase
      inhibitor (TKI) vandetanib. However, this metric failed in overall survival (OS)
      prediction. In the present proof of concept study, we aimed to explore the
      prognostic value of intratumoral textural features (TF) as well as volumetric
      parameters (total lesion glycolysis, TLG) derived by pre-therapeutic 18F-FDG PET.
      METHODS: Eighteen patients with progressive MTC underwent baseline 18F-FDG PET/CT
      prior to and 3 months after vandetanib initiation. By manual segmentation of the
      tumor burden at baseline and follow-up PET, intratumoral TF and TLG were
      computed. The ability of TLG, imaging-based TF, and clinical parameters
      (including age, tumor marker doubling times, prior therapies and RET (rearranged
      during transfection) mutational status) for prediction of both PFS and OS were
      evaluated. RESULTS: The TF Complexity and the volumetric parameter TLG obtained
      at baseline prior to TKI initiation successfully differentiated between low- and
      high-risk patients. Complexity allocated 10/18 patients to the high-risk group
      with an OS of 3.3 y (vs. low-risk group, OS = 5.3 y, 8/18, AUC = 0.78, P = 0.03).
      Baseline TLG designated 11/18 patients to the high-risk group (OS = 3.5 y vs. low
      risk group, OS = 5 y, 7/18, AUC = 0.83, P = 0.005). The Hazard Ratio for cancer
      related death was 6.1 for Complexity (TLG, 9.5). Among investigated clinical
      parameters, the age at initiation of TKI treatment reached significance for PFS
      prediction (P = 0.02, OS, n.s.). CONCLUSIONS: The TF Complexity and the
      volumetric parameter TLG are both independent parameters for OS prediction.

PMID- 30206774
TI  - Usefulness of sternal closure with bioresorbable plate in respiratory function
      after coronary artery bypass grafting.
AB  - OBJECTIVE: The aim of our study is to investigate that sternal reconstruction
      using bioresorbable plate in median sternotomy may reduce postoperative
      respiratory dysfunction when compared with wire cerclage only. METHODS: We
      reviewed 107 patients who were undergone coronary artery bypass grafting with
      median sternotomy. Patients were divided into two groups; patients underwent
      sternal reconstruction with bioresorbable plate and wire cerclage (S group, n =
      56), patients with wire cerclage only (N group, n = 51), and perioperative
      respiratory function and postoperative pain score data were analyzed and compared
      between two groups. RESULTS: There was no significantly difference in
      preoperative respiratory function in both groups. However, in postoperative
      change rate of respiratory function, N group had significant decrease compared
      with S group in vital capacity (VC) (N: S = 74.8 +/- 12.4: 85.2 +/- 14.8%, p =
      0.020), VC as a percentage of predicated VC (N: S = 75.0 +/- 12.5: 86.4 +/-
      15.1%, p = 0.012), and forced expiratory volume in the first second (N: S = 73.7
      +/- 9.2: 85.3 +/- 16.4%, p = 0.012). In Prince Henry Pain Scale, there were
      significantly more in N group compared with S group (N: S = 3.4 +/- 1.0: 2.6 +/-
      1.4, p = 0.003). CONCLUSION: Sternal fixation with bioresorbable plate could
      reduce impairment of postoperative respiratory function in comparison to wire
      cerclage only.

PMID- 30206776
TI  - Golimumab in inflammatory bowel diseases: present and future scenarios.
AB  - Golimumab is the third anti-TNF agent approved for the treatment of ulcerative
      colitis. Despite initial success demonstrated by PURSUIT trials, only few real
      life studies have been published evaluating its efficacy and safety in clinical
      practice. Its subcutaneous route and monthly administration represent an
      advantage in patient compliance, respectively, vs infliximab (intravenous) and
      adalimumab (two doses per month). The most important weakness of the molecule
      which often leads clinicians to choose another anti-TNF is the impossibility to
      dose escalate or reduce the frequency of administrations in case of secondary
      failure; ongoing studies are trying to solve this problem by monitoring drug
      levels and the eventual presence of neutralizing anti-drug antibodies. No
      advantage has still been demonstrated for combination therapy of golimumab with
      immunosuppressants and further studies are necessary to evaluate this aspect.
      Preliminary data also report golimumab efficacy in Crohn's disease with higher
      doses than in ulcerative colitis with an acceptable safety profile. Additional
      studies are needed in this field to confirm the initial findings.

PMID- 30206775
TI  - The Pivotal Role of Pediatric Psychology in Chronic Pain: Opportunities for
      Informing and Promoting New Research and Intervention in a Shifting Healthcare
      Landscape.
AB  - PURPOSE OF REVIEW: In the context of new efforts to formulate more comprehensive
      diagnostic and treatment processes for chronic pain conditions, this review aims
      to provide an overview of some of the most salient developments in the diagnosis
      and clinical treatment of pediatric chronic pain and to delineate the current and
      future role of clinical pediatric psychologists in these efforts. RECENT
      FINDINGS: The acceptance and promotion of the multidisciplinary approach to
      pediatric pain management has had an especially significant impact on the field
      of pediatric psychology. Though chronic pain was historically conceptualized as a
      biomedical problem, psychology is increasingly viewed as a routine, integral, and
      component part of treatment. With this evolving biopsychosocial paradigm,
      pediatric psychology is poised to help shape the development of this field,
      contributing to emerging conceptual and diagnostic frameworks via consultation,
      research, clinical care, and education. This review discusses the role of
      pediatric psychologists as collaborators in emerging diagnostic and assessment
      frameworks, leaders in pain-related research, drivers of clinical care, and
      educators for providers, patients, and the lay public. With increased
      opportunities to enhance the conceptualization and treatment of pediatric pain,
      pediatric psychologists have an important role to play in reducing the prevalence
      and persistence of pediatric pain.

PMID- 30206777
TI  - A case of gastric cancer with delayed onset of tumor reduction effect by
      nivolumab therapy.
AB  - Immune checkpoint inhibitors may have different clinical effects compared with
      conventional anticancer drugs. An 85-year-old male received chemotherapy for
      recurrent gastric cancer. As liver metastasis progressed, nivolumab was
      introduced as a fourth line treatment. Progression of liver metastasis in size
      was observed in CT after 3 courses of nivolumab therapy. Nivolumab treatment was
      discontinued, because the general condition of the patient also worsened.
      However, his general condition improved as hepatobiliary enzyme levels,
      inflammatory response, and tumor markers improved. Liver metastasis was shrinking
      on the image, so we resumed nivolumab therapy. To the authors' knowledge, this is
      the first case of pseudoprogression undergoing immunotherapy for gastric cancer.
      In this case, the antitumor effect was exhibited in a delayed manner and the
      tumor shrinkage was obtained.

PMID- 30206778
TI  - Mechanisms of network evolution: a focus on socioecological factors, intermediary
      mechanisms, and selection pressures.
AB  - Since group-living animals are embedded in a network of social interactions,
      socioecological factors may not only affect individual behavioral strategies but
      also the patterning of group-level social interactions, i.e., the network
      structure. These co-variations between socioecological factors, individual
      behavior, and group-level structure are important to study since ecological
      factors may strongly influence animal health outcomes and reproductive success.
      Besides factors such as social information and/or infectious agents, with far
      reaching individual fitness consequences, seem independent of individuals' own
      social interactions but directly affected by the topology of the social network.
      This paper reviews how socio-ecological pressures, i.e., causal factors (food
      distribution, predation, and infectious agent risk), via intermediary mechanisms
      (stress, information sharing, and mating system), may affect individual social
      behavior and consequently, social network topology. We also discuss how
      evolutionary driving forces, genetic (i.e., genes) and cultural (i.e., learned
      behavior) selection, may result in a specific composition of individuals' social
      strategies that produce network topologies that might be optimized to specific
      socio-ecological conditions. We conclude that studies focusing on whether and how
      well networks resist changing conditions might provide a better understanding of
      the rules underlying individual behavior, which in turn influences network
      topology-a process we have called network evolution. Evolutionary processes may
      favor a group phenotypic composition, thus a network topology. This has been
      referred to as a "collective social niche construction".

PMID- 30206779
TI  - Extended Right Hepatectomy and Inferior Vena Cava Graft Replacement for En Bloc
      Resection of Hepatocellular Carcinoma with Cavo-Hepatic Venous Confluence
      Invasion.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) associated with tumor extension in the
      portal vein, hepatic vein, or inferior vena cava (IVC) is traditionally
      considered an advanced stage of disease to which palliative radiotherapy or
      sorafenib chemotherapy is proposed.1,2 Recent studies have shown a significant
      survival benefit in patients treated with R0 liver resection.3-5 METHODS: We
      describe the case of a 45-year-old female patient presenting with a voluminous
      HCC developed in a non-cirrhotic liver with a tumor thrombus obstructing the
      retrohepatic IVC and the middle hepatic vein termination. Initial treatment
      included two cycles of selective internal radiation therapy with Yttrium 90 and
      sorafenib treatment for 1 year. Re-evaluation revealed a significant reduction of
      the tumor and compensative hypertrophy of the left liver lobe, enabling surgical
      resection. RESULTS: The procedure included anatomic right hepatic
      trisectionectomy with caudate lobectomy and retrohepatic IVC graft replacement.
      Total liver vascular exclusion with intrapericardial IVC control enabled en bloc
      R0 resection of the tumor and the floating tumor thrombus in the cavo-hepatic
      venous confluence. Total liver vascular exclusion duration was 20 min, for a
      total warm liver ischemia of 40 min. The duration of the operation was 240 min
      and blood loss was 700 mL. The patient was discharged on postoperative day 15 and
      was free of disease 6 months post-surgery. CONCLUSION: Liver surgery with complex
      vascular resections for HCC with major vascular invasion should be considered a
      valid therapeutic option in high-volume hepatobiliary centers.

PMID- 30206780
TI  - Direct amide 15N to 13C transfers for solid-state assignment experiments in
      deuterated proteins.
AB  - The assignment of protein backbone and side-chain NMR chemical shifts is the
      first step towards the characterization of protein structure. The recent
      introduction of proton detection in combination with fast MAS has opened up novel
      opportunities for assignment experiments. However, typical 3D sequential
      assignment experiments using proton detection under fast MAS lead to signal
      intensities much smaller than the theoretically expected ones due to the low
      transfer efficiency of some of the steps. Here, we present a selective 3D
      experiment for deuterated and (amide) proton back-exchanged proteins where
      polarization is directly transferred from backbone nitrogen to selected backbone
      or sidechain carbons. The proposed pulse sequence uses only 1H-15N cross
      polarization (CP) transfers, which are, for deuterated proteins, about 30% more
      efficient than 1H-13C CP transfers, and employs a dipolar version of the INEPT
      experiment for N-C transfer. By avoiding HN-C (HN stands for amide protons) and C
      C CP transfers, we could achieve higher selectivity and increased signal
      intensities compared to other pulse sequences containing long-range CP transfers.
      The REDOR transfer is designed with an additional selective pi pulse, which
      enables the selective transfer of the polarization to the desired 13C spins.

PMID- 30206781
TI  - Epigenetic modulation of FOXM1-gene interacting network by BET inhibitors in
      breast cancer.
AB  - INTRODUCTION: FOXM1 is a transcription factor that has been implicated in the
      genesis of several tumors by regulating the expression of genes involved in the
      mitotic process. METHODS: Transcriptomic enrichment analysis was performed to
      evaluate deregulated pathways in breast cancer, and relapse-free survival
      associated with the upregulated genes of FOXM1 signature was explored using the
      KM Plotter online tool. Treatment with bromodomain and extraterminal (BET)
      inhibitor JQ1 was explored in breast cancer cell lines to evaluate FOXM1 by qPCR
      and proliferation by MTT colorimetric assays. RESULTS: The FOXM1 gene signature
      was clearly deregulated in breast cancer patients, particularly in the basal-like
      subgroup where it was linked with detrimental prognosis. Treatment with the BET
      inhibitor JQ1 reduced the expression of FOXM1, decreasing cell proliferation in a
      panel of cell lines, being more active in the basal-like subtype, MDA-MB-231 and
      HS-578T. Knockdown of FOXM1 or treatment with JQ1 reduced genes included in the
      FOXM1 signature. Similarly, genes downregulated by the FOXM1 small interfering
      RNA approach were associated with detrimental outcome in breast cancer patients.
      Finally, we observed that FOXM1 was amplified in the triple-negative breast
      cancer subtype in around 15% of patients. CONCLUSION: Our study demonstrates that
      activation of the FOXM1 pathway has a prognostic role in breast cancer. JQ1 can
      modulate the expression of the FOXM1-gene interacting network, opening the
      opportunity for the evaluation of this compound in breast cancer patients.

PMID- 30206782
TI  - Understanding Asthma Phenotypes, Endotypes, and Mechanisms of Disease.
AB  - The model of asthma as a single entity has now been replaced by a much more
      complex biological network of distinct and interrelating inflammatory pathways.
      The term asthma is now considered an umbrella diagnosis for several diseases with
      distinct mechanistic pathways (endotypes) and variable clinical presentations
      (phenotypes). The precise definition of these endotypes is central to asthma
      management due to inherent therapeutic and prognostic implications. This review
      presents the molecular mechanisms behind the heterogeneity of airway inflammation
      in asthmatic patients. Asthma endotypes may be broadly regarded as type 2 (T2)
      high or T2-low. Several biologic agents have been approved for T2-high asthma,
      with numerous other therapeutics that are incipient and similarly targeted at
      specific molecular mechanisms. Collectively, these advances have shifted existing
      paradigms in the approach to asthma to tailor novel therapies.

PMID- 30206783
TI  - Impact of Gastroesophageal Reflux Disease on Mucosal Immunity and Atopic
      Disorders.
AB  - Atopic disorders and gastroesophageal reflux disease (GERD) are some of the most
      common medical conditions treated by primary care physicians and specialists
      alike. The observation that atopic disorders, like asthma, allergic rhinitis and
      sinusitis, food allergies, atopic dermatitis, contact dermatitis, and
      eosinophilic esophagitis are common comorbidities in patients with GERD raises
      the question of the nature of the relationship that may exist between GERD and
      atopic disorders. In this article, we review the pathophysiology of GERD, its
      effect on the immune system, the effect of acid-blocking medications on allergic
      responses, as well as several common atopic conditions that have been associated
      with GERD including asthma, chronic rhinosinusitis (CRS), allergic rhinitis (AR),
      atopic dermatitis (AD), contact dermatitis (CD), food allergies, proton pump
      inhibitor (PPI)-responsive esophageal eosinophilia (PPI-REE), and eosinophilic
      esophagitis (EoE). In each condition, the evidence of a causal link is not
      definitive. Although the relationship between asthma and GERD remains
      controversial, evidence suggests that a subset of asthma patients with documented
      GERD may experience improved asthma control following appropriate treatment of
      GERD. The relationship of GERD to allergic rhinitis and chronic sinusitis is
      weak; however, studies support the concept that treatment of frequent episodes of
      GERD can have a positive effect on rhinitis and sinusitis overall. The
      relationship between allergic sensitization and GERD is likely bidirectional.
      GERD may induce changes in the mucosal immune system that may favor the
      development of food allergy and allergic sensitization to aeroallergens; however,
      the underlying mechanisms have not been established.

PMID- 30206784
TI  - IFSO 2018 23rd World Congress.

PMID- 30206785
TI  - Anastomotic Strictures After Roux-en-Y Gastric Bypass: a Cohort Study from the
      Scandinavian Obesity Surgery Registry.
AB  - BACKGROUND: Roux-en-Y gastric bypass (RYGB) is the most common bariatric
      procedure worldwide. Anastomotic stricture is a known complication of RYGB. The
      aim was to explore the incidence and outcomes of strictures within the
      Scandinavian Obesity Surgery Registry (SOReg). METHOD: SOReg included prospective
      data from 36,362 patients undergoing bariatric surgery in the years 2007-2013.
      Outcomes were recorded at 30-day and at 1-year follow-up according to the
      standard SOReg routine. The medical charts of patients suffering from stricture
      after RYGB were requested and assessed. SETTING: National bariatric surgery
      registry RESULTS: Anastomotic stricture within 1 year of surgery was confirmed in
      101 patients representing an incidence of 0.3%. Risk factors for stricture were
      patient age above 60 years (odds ratio (OR), 6.2 95% confidence interval (CI) 2.7
      14.3), circular stapled gastrojejunostomy (OR 2.7, 95% CI 1.4-5.5), postoperative
      anastomotic leak (OR 8.9 95%, CI 4.7-17.0), and marginal ulcer (OR 30.0, 95% CI
      19.2-47.0). Seventy-five percent of the strictures were diagnosed within 70 days
      of surgery. Two dilatations or less was sufficient to successfully treat 50% of
      patients. Ten pecent of patients developed perforation during dilatation, and the
      risk of perforating at each dilatation was 3.8%. Perforation required surgery in
      six cases but there was no mortality. Strictures in SOReg may be underreported,
      which could explain the low incidence in the study. CONCLUSION: Most strictures
      present within 2 months and are successfully treated with two dilatations or
      less. Dilating a strictured gastrojejunostomy entails a risk of perforation
      (3.8%).

PMID- 30206787
TI  - Escovopsis kreiselii specialization to its native hosts in the fungiculture of
      the lower attine ant Mycetophylax morschi.
AB  - Parasite-host associations are widespread in nature and the fungus-growing ants
      are considered model organisms to study such interactions. These insects
      cultivate basidiomycetous fungi for food, which are threatened by mycotrophic
      fungi in the genus Escovopsis. Although recently described from colonies of the
      lower attine ant Mycetophylax morschi, the biology and pathogenicity of
      Escovopsis kreiselii are unknown. Herein, we evaluated the interaction of E.
      kreiselii with fungi cultivated by M. morschi (native hosts) and with a fungus
      cultivated by another attine ant species (non-native host). In addition, we
      examined the physical interactions between hypha of E. kreiselii and hypha from
      its native hosts using scanning electron microscopy. Escovopsis kreiselii
      inhibited the growth of fungal cultivars by 24% or more (with exception of one
      isolate), when compared to the fungal cultivars growing alone. Escovopsis
      kreiselii is attracted towards its native hosts through chemotaxis and inhibition
      occurs when there is physical contact with the hyphae of the fungal cultivar. As
      reported for Escovopsis parasites associated with leafcutter ants (higher
      attines), E. kreiselii growth increased in the presence of its native hosts, even
      before contact between both fungi occurred. In interactions with the fungal
      cultivar that is not naturally infected by E. kreiselii (non-native host), it
      caused inhibition but not at the same magnitude as in native hosts. Multiple
      lines of evidence suggest that E. kreiselii is an antagonist of the fungus
      cultivated by M. morschi and can chemically recognize such fungus.

PMID- 30206788
TI  - [Explaining discrepancies in self-reported quality of life in frail older people:
      a mixed-methods study].
AB  - Most research on (multidimensional) frailty focuses on deficits and risks of
      adverse outcomes. However, frail older people can still report positive outcomes,
      such as a relatively high QoL. In order to develop more positively oriented
      prevention strategies, this exploratory study aimed (a) to identify
      characteristics related to QoL among frail older people; and (b) to explain
      discrepancies between higher and lower levels of QoL, with a specific focus on
      strengths frail older people with a higher QoL still may have. Quantitative and
      qualitative data was gathered by means of semi-structured interviews with Flemish
      community-dwelling, frail older people with higher (n = 16) and lower QoL levels
      (n = 18). Quantitative analyses showed that frail older people with a higher QoL
      were older, had lower levels of psychological frailty, and reported higher
      meaning in life compared to those with a lower QoL. Outcomes of qualitative
      analysis showed that participants in the high QoL subgroup adapted more
      effectively to difficulties, had more things in prospect, performed more
      activities, and were more satisfied with their social network compared to the low
      QoL subgroup. To conclude, this exploratory study suggests possibilities to
      promote and improve QoL by strengthening specific resources among frail older
      people.Please note that an English version of this article has been published in
      BMC Geriatrics: van der Vorst A, Zijlstra GAR, De Witte N, Vogel RGM, Schols
      JMGA, Kempen GIJM, D-SCOPE Consortium. Explaining discrepancies in self-reported
      quality of life in frail older people: a mixed-methods study. BMC Geriatr.
      2017;17(1): 251. https://doi.org/10.1186/s12877-017-0641-y .

PMID- 30206790
TI  - First Opioid Prescription and Subsequent High-Risk Opioid Use: a National Study
      of Privately Insured and Medicare Advantage Adults.
AB  - BACKGROUND: National guidelines make recommendations regarding the initial opioid
      prescriptions, but most of the supporting evidence is from the initial episode of
      care, not the first prescription. OBJECTIVE: To examine associations between
      features of the first opioid prescription and high-risk opioid use in the 18
      months following the first prescription. DESIGN: Retrospective cohort study using
      data from a large commercial insurance claims database for 2011-2014 to identify
      individuals with no recent use of opioids and follow them for 18 months after the
      first opioid prescription. PARTICIPANTS: Privately insured patients aged 18-64
      and Medicare Advantage patients aged 65 or older who filled a first opioid
      prescription between 07/01/2011 and 06/30/2013. MAIN OUTCOMES AND MEASURES: High
      risk opioid use was measured by having (1) opioid prescriptions overlapping for 7
      days or more, (2) opioid and benzodiazepine prescriptions overlapping for 7 days
      or more, (3) three or more prescribers of opioids, and (4) a daily dosage
      exceeding 120 morphine milligram equivalents, in each of the six quarters
      following the first prescription. KEY RESULTS: All three features of the first
      prescription were strongly associated with high-risk use. For example, among
      privately insured patients, receiving a long- (vs. short-) acting first opioid
      was associated with a 16.9-percentage-point increase (95% CI, 14.3-19.5), a daily
      MME of 50 or more (vs. less than 30) was associated with a 12.5-percentage-point
      increase (95% CI, 12.1-12.9), and a supply exceeding 7 days (vs. 3 or fewer days)
      was associated with a 4.8-percentage-point increase (95% CI, 4.5-5.2), in the
      probability of having a daily dosage of 120 MMEs or more in the long term,
      compared to a sample mean of 4.2%. Results for the Medicare Advantage patients
      were similar. CONCLUSIONS: Long-acting formulation, high daily dosage, and longer
      duration of the first opioid prescription were each associated with increased
      high-risk use of opioids in the long term.

PMID- 30206791
TI  - Capsule Commentary on Verma et al., Prevalence and Costs of Discharge Diagnoses
      in Inpatient General Internal Medicine: a Multi-center Cross-sectional Study.

PMID- 30206789
TI  - Effectiveness of Policies and Programs to Combat Adult Obesity: a Systematic
      Review.
AB  - BACKGROUND: This systematic review identifies programs, policies, and built
      environment changes targeting prevention and control of adult obesity and
      evaluates their effectiveness. METHODS: We searched PubMed, CINAHL, PsycINFO, and
      EconLit from January 2000 to March 2018. We included natural experiment studies
      evaluating a program, policy, or built-environment change targeting adult obesity
      and reporting weight/body mass index (BMI). Studies were categorized by primary
      intervention target: physical activity/built environment, food/beverage,
      messaging, or multiple. Two reviewers independently assessed the risk of bias for
      each study using the Effective Public Health Practice Project tool. RESULTS: Of
      158 natural experiments targeting obesity, 17 reported adult weight/BMI outcomes.
      Four of 9 studies reporting on physical activity/built environment demonstrated
      reduced weight/BMI, although effect sizes were small with low strength of
      evidence and high risk of bias. None of the 5 studies targeting the food/beverage
      environment decreased weight/BMI; strength of evidence was low, and 2 studies
      were rated high risk of bias. DISCUSSION: We identified few natural experiments
      reporting on the effectiveness of programs, policies, and built-environment
      changes on adult obesity. Overall, we found no evidence that policies intending
      to promote physical activity and healthy eating had beneficial effects on
      weight/BMI and most studies had a high risk of bias. Limitations include few
      studies met our inclusion criteria; excluded studies in children and those not
      reporting on weight/BMI outcomes; weight/BMI reporting was very heterogeneous.
      More high-quality research, including natural experiments studies, is critical
      for informing the population-level effectiveness of obesity prevention and
      control initiatives in adults.

PMID- 30206792
TI  - Pap Testing in the USA and Potential Association with HPV Vaccination: a Cross
      sectional Analysis of the BRFSS Data (2007-2016).

PMID- 30206793
TI  - Value-Based Reimbursement in Collectively Financed Healthcare Requires Monitoring
      of Socioeconomic Patient Data to Maintain Equality in Service Provision.
AB  - Value-based purchasing is increasingly discussed in association with efforts to
      develop modern healthcare systems. These models are the most recent example of
      models derived from health economics research intended to reform collectively
      financed healthcare. Previous examples have ranged from creation of pseudo
      markets to opening these markets for competition between publicly and privately
      owned enterprises. Most value-based purchasing models tend to ignore that health
      service provision in collectively financed settings is based on an insurance with
      political, social obligations attached that challenge the notion of free market
      and individualist premises which these models rest on. Central social issues
      related to healthcare in any modern complex society, such as inequality in
      service provision, can all too easily "disappear" in value-based reform efforts.
      Based on an analysis of Swedish policy development, we contend that management
      information systems need to be extended to allow routine monitoring of
      socioeconomic data when models such as value-based purchasing are introduced in
      collectively financed health services. The experiences from Sweden are important
      for health policy in Europe and other regions with collectively financed
      healthcare plans.

PMID- 30206794
TI  - Correction to: Vascular Ehlers-Danlos Syndrome Presenting as a Pulsatile Neck
      Mass: a Case Report and Review of Literature.
AB  - The article was originally published electronically on the publisher's internet
      portal (currently SpringerLink) with open access.

PMID- 30206795
TI  - Repeated Spiral Drawings in Essential Tremor: a Possible Limb-Based Measure of
      Motor Learning.
AB  - To investigate changes in tremor severity over repeated spiral drawings to assess
      whether learning deficits can be evaluated directly in a limb in essential tremor
      (ET). A motor learning deficit in ET, possibly mediated by cerebellar pathways,
      has been established in eye-blink conditioning studies, but not paradigms
      measuring from an affected, tremulous limb. Computerized spiral analysis captures
      multiple characteristics of Archimedean spirals and quantifies performance
      through calculated indices. Sequential spiral drawing has recently been suggested
      to demonstrate improvement across trials among ET subjects. One hundred and sixty
      one ET and 80 age-matched control subjects drew 10 consecutive spirals on a
      digitizing tablet. Degree of severity (DoS), a weighted, computational score of
      spiral execution that takes into account spiral shape and line smoothness,
      previously validated against a clinical rating scale, was calculated in both
      groups. Tremor amplitude (Ampl), an independent index of tremor size, measured in
      centimeters, was also calculated. Changes in DoS and Ampl across trials were
      assessed using linear regression with slope evaluations. Both groups demonstrated
      improvement in DoS across trials, but with less improvement in the ET group
      compared to controls. Ampl demonstrated a tendency to worsen across trials in ET
      subjects. ET subjects demonstrated less improvement than controls when drawing
      sequential spirals, suggesting a possible motor learning deficit in ET, here
      captured in an affected limb. DoS improved independently of Ampl, showing that
      DoS and Ampl are separable motor physiologic components in ET that may be
      independently mediated.

PMID- 30206796
TI  - Barriers to the identification of familial hypercholesterolemia among primary
      care providers.
AB  - Familial hypercholesterolemia (FH) is severely underdiagnosed in the USA. Primary
      care providers are well-positioned to identify FH cases; however, universal FH
      screening is not routinely implemented in practice. The aim of the present study
      was to identify perceived barriers to FH screening among primary care physicians
      in Minnesota. A questionnaire assessed FH screening practices, knowledge, and
      perceived barriers to FH screening. The questionnaire, sent electronically to
      internal and family medicine physicians in Minnesota (N = 1932) yielded a
      conservative estimated response rate of 9% (N = 173). Although 92% of
      participants reported themselves responsible for identifying individuals with FH,
      30% did not routinely perform screening in practice. Only 50% of participants
      were able to correctly identify the risk of FH to first-degree relatives of
      individuals with FH. Challenges incorporating lipid and family history data was
      the most frequently endorsed barrier to FH screening (34%). A majority of
      participants endorsed a clinical decision support system that flags individuals
      at high risk for FH (62%) and an algorithm with cholesterol levels and lipid
      disorders (56%) as means of facilitating FH screening. Although the
      generalizability of the findings is unknown, the results underscore the need for
      increased provider education regarding FH and suggest an FH screening strategy
      incorporating a clinical decision support system, screening algorithm, and
      support from other healthcare providers.

PMID- 30206797
TI  - The Glasgow Norms: Ratings of 5,500 words on nine scales.
AB  - The Glasgow Norms are a set of normative ratings for 5,553 English words on nine
      psycholinguistic dimensions: arousal, valence, dominance, concreteness,
      imageability, familiarity, age of acquisition, semantic size, and gender
      association. The Glasgow Norms are unique in several respects. First, the corpus
      itself is relatively large, while simultaneously providing norms across a
      substantial number of lexical dimensions. Second, for any given subset of words,
      the same participants provided ratings across all nine dimensions (33
      participants/word, on average). Third, two novel dimensions-semantic size and
      gender association-are included. Finally, the corpus contains a set of 379
      ambiguous words that are presented either alone (e.g., toast) or with information
      that selects an alternative sense (e.g., toast (bread), toast (speech)). The
      relationships between the dimensions of the Glasgow Norms were initially
      investigated by assessing their correlations. In addition, a principal component
      analysis revealed four main factors, accounting for 82% of the variance
      (Visualization, Emotion, Salience, and Exposure). The validity of the Glasgow
      Norms was established via comparisons of our ratings to 18 different sets of
      current psycholinguistic norms. The dimension of size was tested with megastudy
      data, confirming findings from past studies that have explicitly examined this
      variable. Alternative senses of ambiguous words (i.e., disambiguated forms), when
      discordant on a given dimension, seemingly led to appropriately distinct ratings.
      Informal comparisons between the ratings of ambiguous words and of their
      alternative senses showed different patterns that likely depended on several
      factors (the number of senses, their relative strengths, and the rating scales
      themselves). Overall, the Glasgow Norms provide a valuable resource-in
      particular, for researchers investigating the role of word recognition in
      language comprehension.

PMID- 30206798
TI  - Evidence for co-invasion events: different chigger species (Actinotrichida,
      Trombidioidea: trombiculidae) share a host.
AB  - Cases of co-invasion of various chigger species parasitizing murids and cricetids
      in various habitats were analysed using morphological and molecular approaches.
      Here we provide evidence for 25 new cases of co-parasitism of chigger mites on
      rodent hosts (Myodes glareolus, Apodemus flavicollis, Apodemus agrarius)
      accounting for 8.6% of all host-parasite associations observed in this study. The
      results confirm higher incidence of co-parasitism in vertebrate-associated
      Parasitengona mites compared to arthropod-associated ones. Among factors
      influencing the occurrence of co-parasitism in Trombiculidae the body
      constitution and year-round availability of hosts associated with lower host
      specificity of larvae should be considered.

PMID- 30206799
TI  - Patterns of Grey Matter Atrophy at Different Stages of Parkinson's and
      Alzheimer's Diseases and Relation to Cognition.
AB  - Using MRI, a characteristic pattern of grey matter (GM) atrophy has been
      described in the early stages of Alzheimer's disease (AD); GM patterns at
      different stages of Parkinson's disease (PD) have been inconclusive. Few studies
      have directly compared structural changes in groups with mild cognitive
      impairment (MCI) caused by different pathologies (AD, PD). We used several
      analytical methods to determine GM changes at different stages of both PD and AD.
      We also evaluated associations between GM changes and cognitive measurements.
      Altogether 144 subjects were evaluated: PD with normal cognition (PD-NC; n = 23),
      PD with MCI (PD-MCI; n = 24), amnestic MCI (aMCI; n = 27), AD (n = 12), and age
      matched healthy controls (HC; n = 58). All subjects underwent structural MRI and
      cognitive examination. GM volumes were analysed using two different techniques:
      voxel-based morphometry (VBM) and source-based morphometry (SBM), which is a
      multivariate method. In addition, cortical thickness (CT) was evaluated to assess
      between-group differences in GM. The cognitive domain z-scores were correlated
      with GM changes in individual patient groups. GM atrophy in the anterior and
      posterior cingulate, as measured by VBM, in the temporo-fronto-parietal
      component, as measured by SBM, and in the posterior cortical regions as well as
      in the anterior cingulate and frontal region, as measured by CT, differentiated
      aMCI from HC. Major hippocampal and temporal lobe atrophy (VBM, SBM) and to some
      extent occipital atrophy (SBM) differentiated AD from aMCI and from HC.
      Correlations with cognitive deficits were present only in the AD group. PD-MCI
      showed greater GM atrophy than PD-NC in the orbitofrontal regions (VBM), which
      was related to memory z-scores, and in the left superior parietal lobule (CT);
      more widespread limbic and fronto-parieto-occipital neocortical atrophy (all
      methods) differentiated this group from HC. Only CT revealed subtle GM atrophy in
      the anterior cingulate, precuneus, and temporal neocortex in PD-NC as compared to
      HC. None of the methods differentiated PD-MCI from aMCI. Both MCI groups showed
      distinct limbic and fronto-temporo-parietal neocortical atrophy compared to HC
      with no specific between-group differences. AD subjects displayed a typical
      pattern of major temporal lobe atrophy which was associated with deficits in all
      cognitive domains. VBM and CT were more sensitive than SBM in identifying frontal
      and posterior cortical atrophy in PD-MCI as compared to PD-NC. Our data support
      the notion that the results of studies using different analytical methods cannot
      be compared directly. Only CT measures revealed some subtle differences between
      HC and PD-NC.

PMID- 30206800
TI  - Urinary IgM excretion: a reliable marker for adverse pregnancy outcomes in women
      with chronic kidney disease.
AB  - OBJECTIVE: Chronic kidney disease (CKD) pregnancies are at high risk of
      developing adverse outcomes. In non-pregnant subjects with CKD, higher urinary
      IgM levels are associated with poor renal survival and higher rates of
      cardiovascular deaths. In this study, we assessed whether urinary IgM levels are
      associated with an increased risk of adverse pregnancy outcomes (APO) in CKD
      pregnancies. METHODS: We performed a nested case-control study within a cohort of
      CKD patients with singleton pregnancies attended at a tertiary care hospital. The
      study included 90 CKD patients who eventually developed one or more APO and 77
      CKD patients who did not. Urinary IgM excretion was determined from the 24-h
      urine samples at enrollment by an ultrasensitive enzyme immunoassay. RESULTS: The
      risk for combined APO and for preeclampsia (PE) was higher among women with
      urinary IgM and proteinuria levels values in the highest quartile or with CKD
      stages 4-5 (odds ratios, OR >= 2.9), compared with the lowest quartile or with
      CKD stage 1. Urinary IgM levels were more closely associated with the risk of
      either combined or specific APO (PE, preterm birth, and for having a small-for
      gestational-age infant; OR >= 5.9) than either the degree of total proteinuria or
      CKD stages. Among patients with CKD stage 1, the risk of combined APO, PE, and
      preterm birth was higher in women with urinary IgM levels values in the highest
      quartile (OR >= 4.8), compared with the three lower quartiles, independently of
      proteinuria. CONCLUSION: In CKD pregnancies, at the time of initial evaluation,
      proteinuria and CKD stage are associated with increased risk of combined APO.
      However, urinary IgM concentrations appear to be better predictors of an adverse
      outcome and may be useful for risk stratification in CKD pregnancies.

PMID- 30206803
TI  - Glomangiopericytoma of the Nasal Cavity with CTNNB1 p.S37C Mutation: A Case
      Report and Literature Review.
AB  - Glomangiopericytoma (GPC) is a rare mesenchymal tumor arising from the nasal
      cavity or paranasal sinuses. GPC was categorized as a borderline and low
      malignant-potential tumor by the World Health Organization in 2005 and accounts
      for less than 0.5% of all sinonasal tumors. We report a case of GPC in a 74-year
      old woman with a history of recurrent epistaxis and nasal obstruction. A reddish
      tumor was seen in the right nasal cavity. Enhanced computed tomography showed a
      mass lesion occupying the right nasal cavity. The tumor, which originated from
      the nasal septum in the olfactory fissure area, was resected with 5-mm mucosal
      margins by endoscopic sinus surgery. Histologic examination revealed a uniform
      proliferation of oval-to-short spindle-shaped cells beneath the epithelium.
      Immunohistologic analysis demonstrated the tumor cells were positive for alpha
      smooth muscle actin, beta-catenin and Vimentin, and negative for AE1/AE3, Bcl-2,
      CD34, CD117, Factor VIIIR Ag, S-100 protein, or STAT6. The percentage of Ki-67
      positive cells was approximately 5%. Genetic analysis using next-generation
      sequencing revealed a missense mutation in the CTNNB1 gene (c.110C > G, p.S37C).
      While other CTNNB1 mutations have been described in GPC; this is the first report
      of this specific mutation. The mutation was confirmed using Sanger sequencing.

PMID- 30206802
TI  - Combined radiotherapy with nivolumab for extracranial metastatic malignant
      melanoma.
AB  - PURPOSE: We retrospectively evaluated the tumor regression after radiotherapy in
      combination with the immune checkpoint inhibitor nivolumab for metastatic
      melanoma. MATERIALS AND METHODS: We evaluated the extracranial metastatic
      melanoma lesions to which concomitant radiotherapy with nivolumab was
      administered from June 2015 to February 2017. Tumor volume and maximum diameter
      were measured at the time of pre-radiotherapy and best response, and the tumor
      reduction rate was assessed in two ways that our hospital adopts: tumor volume
      and diameter. RESULTS: Seven lesions in five patients were evaluated. The median
      time from the start of nivolumab treatment to the start of radiotherapy was 5
      months (range 0-22 months). The objective response rate was 85.7% in the
      evaluation by tumor volume and 42.9% by maximum diameter of the tumor. The
      objective complete response rate was 28.6% in evaluation by tumor volume and
      14.3% by maximum dia. The 1-year tumor control rate was 62.5%. The 1- and 2-year
      overall survival rate after nivolumab treatment were 75% and 50%, respectively.
      Two patients who obtained a complete response had presented with vitiligo.
      CONCLUSION: The combination of radiotherapy and nivolumab treatment produced
      favorable responses. Vitiligo may be correlated with a good response to
      concomitant radiotherapy with nivolumab.

PMID- 30206801
TI  - Assessing and Treating Chronic Pain in Patients with End-Stage Renal Disease.
AB  - Pain is one of the most common symptoms among patients with end-stage renal
      disease (ESRD), and is often under recognized and not adequately managed in
      hemodialysis (HD) patients. Barriers to adequate pain management include poor
      awareness of the problem, insufficient medical education, fears of possible drug
      related side effects, and common misconceptions about the inevitability of pain
      in elderly and HD patients. Caregivers working in HD should be aware of the
      possible consequences of inadequate pain assessment and management. Common pain
      syndromes in HD patients include musculoskeletal diseases and metabolic
      neuropathies, associated with typical intradialytic pain. Evaluating the
      etiology, nature, and intensity of pain is crucial for choosing the correct
      analgesic. A mechanism-based approach to pain management may result in a better
      outcome. Pharmacokinetic considerations on clearance alterations and possible
      toxicity in patients with ESRD should drive the right analgesic prescription.
      Comorbidities and polymedications may increase the risk of drug-drug
      interactions, therefore drug metabolism should be taken into account when
      selecting analgesic drugs. Automedication is common among HD patients but should
      be avoided to reduce the risk of hazardous drug administration. Further research
      is warranted to define the efficacy and safety of analgesic drugs and techniques
      in the context of patients with ESRD as generalizing information from studies
      conducted in the general population could be inappropriate and potentially
      dangerous. A multidisciplinary approach is recommended for the management of
      complex pain syndromes in frail patients, such as those suffering from ESRD.

PMID- 30206804
TI  - Glycyrrhizic Acid Alleviates 6-Hydroxydopamine and Corticosterone-Induced
      Neurotoxicity in SH-SY5Y Cells Through Modulating Autophagy.
AB  - Recent researches have shown that autophagy is associated with the pathogenesis
      of neurodegenerative disorders, but there is no paper to investigate the effects
      of autophagy modulation on Parkinson's disease depression (PDD). In addition,
      glycyrrhizic acid (GA), the major bioactive ingredient of Radix glycyrrhizae, can
      induce autophagy and ease rotenone-induced Parkinson's disease (PD). However,
      there is also no paper to study the action and molecular mechanisms of GA on PDD.
      In this research, we built the injury model of SH-SY5Y cells through 6
      hydroxydopamine (6-OHDA) and corticosterone (CORT). Then, our results showed that
      GA markedly increased the viability and decreased the apoptosis in SH-SY5Y cells
      after pre-treating with 6-OHDA and CORT. Moreover, GA notably decreased the
      expressions of alpha-Syn and p-S1292-LRRK2 proteins, and significantly increased
      the levels of CREB and BDNF proteins. Previous papers have suggested that CORT
      contributed to dopaminergic neurodegeneration via the glucocorticoid
      (GC)/glucocorticoid receptor (GR) interaction, and our results showed that GA
      reduced GC level and hypothalamic-pituitary-adrenal (HPA) activity in SH-SY5Y
      cells by regulating GR signaling pathway. Furthermore, mechanism investigations
      also showed that GA had the ability to up-regulate the conversion of LC3B II/I
      and the expression of Beclin-1, and induce autophagy in SH-SY5Y cells, which were
      reversed by the autophagy inhibitor 3-methyladenine (3-MA). Collectively, these
      findings proved that GA exerted efficient activity against neurotoxicity in SH
      SY5Y cells induced by 6-OHDA and CORT via activation of autophagy, which should
      be developed as an efficient candidate for treating PDD in the future.

PMID- 30206805
TI  - Adipose insulin resistance is associated with cardiovascular risk factors in
      polycystic ovary syndrome.
AB  - PURPOSE: The effects of adipose insulin resistance on cardiovascular risk factors
      in polycystic ovary syndrome (PCOS) remain largely unknown. We aimed to
      investigate associations between adipose insulin resistance and cardiovascular
      risk factors in PCOS. METHODS: A total of 207 PCOS and 47 non-PCOS women were
      recruited from a large reproductive medicine center in this cross-sectional
      study. The PCOS diagnosis was based on the Rotterdam Criteria. The subjects
      received a standard oral glucose tolerance test. Adipose insulin resistance was
      evaluated using a validated index (adipose-IR = fasting insulin * free fatty acid
      concentrations). RESULTS: The women with PCOS showed a higher adipose-IR index,
      and the adipose-IR index was tightly associated with the blood pressure, glucose
      and lipid parameters. A total of 98.0% of the women with PCOS in the highest
      adipose-IR quartile showed cardiovascular risk factors (obesity, hypertension,
      glucose intolerance or dyslipidemia), and this percentage was significantly
      higher than the percentage of those in the lowest quartile (32.7%). In addition,
      the percentages of women with three (31.4%) and four (13.7%) cardiovascular risk
      factors were significantly elevated in the highest adipose-IR quartile. The
      multivariable logistic regression analysis indicated that each 1-SD increment in
      the adipose-IR index resulted in higher risks of obesity (OR = 3.18, 95% CI =
      2.12-4.76), hypertension (OR = 1.89, 95% CI = 1.31-2.73), glucose intolerance (OR
      = 2.45, 95% CI = 1.73-3.48), and dyslipidemia (OR = 2.18, 95% CI = 1.57-3.01).
      The C-reactive protein (CRP) level was positively associated with the adipose-IR
      index in women with PCOS (r = 0.45, P < 0.001). CONCLUSIONS: The adipose-IR index
      was associated with cardiovascular risk factors in women with PCOS. Chronic
      inflammation may induce insulin resistance in the adipose tissue of women with
      PCOS.

PMID- 30206806
TI  - Molecular characterization and detection of a new closterovirus identified from
      blackcurrant by high-throughput sequencing.
AB  - Two large contigs with high sequence similarities to several closteroviruses were
      identified by high-throughput sequencing from a blackcurrant plant. The complete
      genome of this new virus was determined to be 17,320 nucleotides. Its genome
      contains ten open reading frames (ORF) that include, in the 5'-3' direction, a
      large ORF encoding a putative viral polyprotein (ORF 1a) and nine ORFs that
      encode RNA-dependent RNA polymerase (RdRp, ORF 1b), p6 (ORF 2), heat shock
      protein 70-like protein (Hsp70h, ORF 3), Hsp-90-like protein (p61, ORF 4), CP
      minor (ORF 5), CP (ORF 6), p17 (ORF 7), p11 (ORF 8), and p26 (ORF 9),
      respectively. BCCV-1 shares nucleotide sequence identities of 43-45% with other 9
      closteroviruses at genome sequences. The amino acid sequence identities between
      BCCV-1 and the closteroviruses were 49-55% (RdRp), 37-41% (Hsp70h), 19-33% (p61),
      26-38% (CPm), and 19-28% (CP), respectively. Phylogenetic analysis of Hsp70h
      sequences placed the new virus with members of genus Closterovirus in the same
      group. The results indicate that this new virus, which is provisionally named as
      Blackcurrant closterovirus 1, should represent a new species of the genus
      Closterovirus. A RT-PCR was developed and used to detect BCCV-1 in more germplasm
      accessions of Ribes spp.

PMID- 30206807
TI  - Multi-country investigation of factors influencing breeding decisions by
      smallholder dairy farmers in sub-Saharan Africa.
AB  - Artificial insemination (AI) and selective bull mating are considered as robust
      methods for dairy cattle breeding. Globally, these methods have been used to
      enhance productivity and realize rapid genetic gains. However, these technologies
      have had low adoption rates in sub-Saharan Africa (SSA). Even though available
      evidence suggests that this is due to various infrastructural and technical
      challenges. There is limited information about what drives this low uptake of AI
      from a farmer's perspective. Therefore, the main objective of this study was to
      determine and characterize factors that influence the choice by smallholder
      farmers between bull service and AI for dairy cow breeding. Further, the
      relationships between the breeding choices and the bio-physical elements of dairy
      farming, mainly, farmer characteristics, household income levels, farm management
      practices, and institutional support structures, were investigated. Data were
      collected through face-to-face interviews from a total of 16,308 small-scale
      dairy farmers in Ethiopia (n = 4679), Kenya (n = 5278), Tanzania (n = 3500), and
      Uganda (n = 2851). The questionnaire was coded in an electronic form using Open
      Data Kit (ODK) platform to allow for real-time data entry and management.
      Descriptive statistics, chi-square test, and a t-test were used to evaluate the
      independent and dependent variables, while logistic regression and factor
      analysis were used to identify factors that influenced farmers' breeding
      decisions. Results showed that there was a significant difference in animal
      husbandry practices between farmers who used artificial insemination (AI) and
      those who practiced bull mating. The majority of farmers who used AI kept
      records, purchased more animal feeds, had more labor by hiring workers whose
      average wages were higher than those of bull service farmers. However, farmers
      who used AI pay more for services such as water access and breeding while their
      service providers had to cover long distances compared to farmers who used bulls.
      This indicates limited access to services and service providers for AI farmers.
      The ratio of AI to bull service users was even for Ethiopia and Kenya, while in
      Uganda and Tanzania, more farmers preferred bull service to AI. It was
      established that the factors that influence farmers' breeding decision were not
      the same across the region. Factors such as farmer's experience in dairy farming,
      influence of the neighbor, farmer's ability to keep records, and management
      practices such as water provision and availability of feeds had a significant
      association (p < 0.001) with AI adoption among dairy farmers. In contrast, large
      herd and large land size negatively influenced AI adoption. Institutional
      settings including cost of AI service and the distance covered by the service
      provider negatively affected (p < 0.001) the choice of AI as a breeding option.
      There was a high probability of continued use of a specific breeding method when
      there was a previous conception success with that same method. Based on the
      results obtained, we recommend that improvement of institutional settings such as
      the availability of AI service providers, as well as better access to services
      such as water, animal feed, and animal health provision, be treated as critical
      components to focus on for enhanced AI adoption. Most importantly, there is a
      need to avail training opportunities to equip farmers with the necessary skills
      for best farm management practices such as record keeping, proper feeding, and
      selective breeding.

PMID- 30206808
TI  - Precise Estimates of Persistence Time for SIS Infections in Heterogeneous
      Populations.
AB  - For a susceptible-infectious-susceptible infection model in a heterogeneous
      population, we derive simple and precise estimates of mean persistence time, from
      a quasi-stationary endemic state to extinction of infection. Heterogeneity may be
      in either individuals' levels of infectiousness or of susceptibility, as well as
      in individuals' infectious period distributions. Infectious periods are allowed
      to follow arbitrary non-negative distributions. We also obtain a new and accurate
      approximation to the quasi-stationary distribution of the process, as well as
      demonstrating the use of our estimates to investigate the effects of different
      forms of heterogeneity. Our model may alternatively be interpreted as describing
      an infection spreading through a heterogeneous directed network, under the
      annealed network approximation.

PMID- 30206809
TI  - Tropical Principal Component Analysis and Its Application to Phylogenetics.
AB  - Principal component analysis is a widely used method for the dimensionality
      reduction of a given data set in a high-dimensional Euclidean space. Here we
      define and analyze two analogues of principal component analysis in the setting
      of tropical geometry. In one approach, we study the Stiefel tropical linear space
      of fixed dimension closest to the data points in the tropical projective torus;
      in the other approach, we consider the tropical polytope with a fixed number of
      vertices closest to the data points. We then give approximative algorithms for
      both approaches and apply them to phylogenetics, testing the methods on simulated
      phylogenetic data and on an empirical dataset of Apicomplexa genomes.

PMID- 30206810
TI  - Clinical significance and potential translation of neural regeneration and
      functional recovery in monkeys after spinal cord injury.

PMID- 30206811
TI  - Detection of Neutral CO Lost During Ionic Dissociation Using Atmospheric Pressure
      Thermal Dissociation Mass Spectrometry (APTD-MS).
AB  - Elucidation of ion dissociation patterns is particularly important to structural
      analysis by mass spectrometry (MS). However, typically, only the charged
      fragments from an ion dissociation event are detected in tandem MS experiments;
      neutrals are not identified. In recent years, we have developed an atmospheric
      pressure thermal dissociation (APTD) technique that can be applied to dissociate
      ions at atmosphere pressure and thus provide one way to characterize neutral
      fragments. In this paper, we focus on the detection of neutral CO resulting from
      amino acid and peptide ion dissociation. In the first set of experiments, several
      protonated amino acids (e.g., + 1 ion of phenylalanine) were found to undergo
      loss of a neutral (s) of total mass 46 Da, a process leading to iminium ion
      formation. We successfully detected the neutral species CO by using a CO sensor,
      UV-Vis and MS analysis following selective CO trapping with a rhodium complex.
      The capture of CO from dissociation of protonated amino acids supports the
      assignment of the loss of 46 Da to neutral losses of CO and H2O, rather than loss
      of formaldehyde or dihydroxycarbene, other possible fragmentation pathways that
      have been subject of debate for a long time. In a second experiment, we used the
      APTD method in combination with the CO detection technique, to demonstrate the
      formation of CO in the conversion of b ions to a ions during peptide ion
      dissociations. These results showed the potential of APTD in the elucidation of
      ion dissociation mechanisms, using simple home-built apparatus. Graphical
      Abstract ?.

PMID- 30206813
TI  - Medical data mining in sentiment analysis based on optimized swarm search feature
      selection.
AB  - In this paper, we propose a novel technique termed as optimized swarm search
      based feature selection (OS-FS), which is a swarm-type of searching function that
      selects an ideal subset of features for enhanced classification accuracy. In
      terms of gaining insights from unstructured medical based texts, sentiment
      prediction is becoming an increasingly crucial machine learning technique. In
      fact, due to its robustness and accuracy, it recently gained popularity in the
      medical industries. Medical text mining is well known as a fundamental data
      analytic for sentiment prediction. To form a high-dimensional sparse matrix, a
      popular preprocessing step in text mining is employed to transform medical text
      strings to word vectors. However, such a sparse matrix poses problems to the
      induction of accurate sentiment prediction model. The swarm search in our
      proposed OS-FS can be optimized by a new feature evaluation technique called
      clustering-by-coefficient-of-variation. In order to find a subset of features
      from all the original features from the sparse matrix, this type of feature
      selection has been a commonly utilized dimensionality reduction technique, and
      has the capability to improve accuracy of the prediction model. We implement this
      method based on a case scenario where 279 medical articles related to 'meaningful
      use functionalities on health care quality, safety, and efficiency' from a
      systematic review of previous medical IT literature. For this medical text
      mining, a multi-class of sentiments, positive, mixed-positive, neutral and
      negative is recognized from the document contents. Our experimental results
      demonstrate the superiority of OS-FS over traditional feature selection methods
      in literature.

PMID- 30206814
TI  - Correction to: Evaluation of Generic Methods to Predict Human Pharmacokinetics
      Using Physiologically Based Pharmacokinetic Model for Early Drug Discovery of
      Tyrosine Kinase Inhibitors.
AB  - The original version of this article unfortunately contained a mistake. Conflict
      of interest statement was incorrect. The corrected COI statement is given below.

PMID- 30206812
TI  - An Update On Medical Treatment for Intracerebral Hemorrhage.

PMID- 30206815
TI  - Limits of continuous neural monitoring in thyroid surgery.

PMID- 30206817
TI  - Changes and determinants of health-related quality of life among people newly
      diagnosed with HIV in China: a 1-year follow-up study.
AB  - PURPOSE: This study aimed to investigate changes in health-related quality of
      life (HRQoL) among people newly diagnosed with HIV and to identify factors
      associated with HRQoL. METHODS: Newly diagnosed HIV-positive individuals were
      consecutively recruited and assessed at baseline and 1-year follow-up after
      diagnosis. HRQoL was measured through the physical health summary score (PHS) and
      mental health summary score (MHS) derived from the Medical Outcomes Study HIV
      Health Survey. Socio-demographic, clinical, and psychological information was
      also collected at both times. Generalized estimating equations were applied to
      explore factors associated with HRQoL in 1 year. RESULTS: A total of 410
      participants were included. After 1 year, significant increases were observed for
      both the mean PHS score (53.5-55.0; p = 0.009) and the mean MHS score (44.2-49.0;
      p < 0.001). Older age (p = 0.024), rural household registration (p = 0.031), HIV
      related symptoms (p < 0.001), and depression (p = 0.014) were negatively
      associated with PHS. Additionally, the negative association between stress and
      PHS increased over time (beta = - 0.07 for the baseline; beta = - 0.18 for the 12
      month follow-up; p < 0.001). HIV-related symptoms, depression, lower social
      support, and higher levels of stress (all p < 0.001) were negatively associated
      with MHS. Additionally, the negative relationship between stress and MHS was
      stronger among participants who were asymptomatic (p = 0.015). CONCLUSION: A
      relatively lower HRQoL among HIV-infected people shortly after HIV diagnosis and
      an increase in HRQoL among people 1 year after HIV diagnosis were observed.
      Additional attention should be paid to individuals of older age, from rural
      areas, with HIV-related symptoms, with depression, with high levels of stress,
      and with a lack of social support.

PMID- 30206816
TI  - Physical activity attenuates the impact of poor physical, mental, and social
      health on total and cardiovascular mortality in older adults: a population-based
      prospective cohort study.
AB  - PURPOSE: To examine the separate and joint associations of physical activity and
      levels of physical, mental, and social health with long-term all-cause and
      cardiovascular disease (CVD) mortality in older adults. METHODS: A cohort of 4008
      individuals representative of the non-institutionalized population of Spain aged
      60 years and older was analyzed. Information on physical activity was self
      reported. Physical and mental health were assessed with the SF-36 questionnaire,
      and social health with a 4-item score on network structure and social engagement.
      Participants were categorized as being in a good, intermediate, or poor health
      according to tertiles of the score in each health dimension. Analyses were
      performed with Cox regression and adjusted for main confounders, including levels
      in the other two health dimensions. RESULTS: Over a median follow-up of 14 years,
      a total of 1811 deaths occurred, 674 due to CVD. Hazard ratios (95% confidence
      interval) for all-cause mortality were 1.35 (1.18-1.55), 1.18 (1.02-1.36), and
      1.37 (1.18-1.58) for poor vs. good physical, mental, and social health,
      respectively (all p trend < 0.001). Being physically active was associated with a
      28% (15-39%), 31% (19-42%), and 19% (5-31%) lower all-cause mortality in
      participants with poor physical, mental, and social health, respectively. In each
      health dimension, physically active individuals with poor health showed a similar
      or lower all-cause mortality than those who had intermediate or good health but
      were physically inactive. Results for CVD mortality were similar to those for all
      cause death. CONCLUSIONS: Physical activity might attenuate the excess all-cause
      and CVD mortality associated with poor physical, mental, and social health.

PMID- 30206818
TI  - Brain structural basis of individual variability in dream recall frequency.
AB  - Recent neuroimaging studies have indicated that inter-individual variability in
      dream recall frequency (DRF) is associated with both resting-state regional
      cerebral blood flow and task-induced brain activations. However, the brain
      structure underpinning this inter-individual variability in DRF remains unclear.
      The aim of the current study is to investigate the relationship between brain
      structural characteristics and DRF. We collected both T1-weighted and diffusion
      tensor magnetic resonance imaging data from 43 healthy volunteers. DRF was
      obtained from a two-week sleep diary with a subjective report of dream recall
      upon waking every morning. General linear model analysis was used to evaluate the
      relationship between brain structural characteristics (cortical volume and white
      matter integrity) and DRF. Not only the cortical volume of the medial portion of
      the right fusiform gyrus and parahippocampal gyrus but also the fractional
      anisotropy of white matter fibers connected to these regions were significantly
      negatively correlated with DRF, and these relationships were not modulated by a
      regular sleep. These findings provide direct evidence that brain structural
      characteristics are associated with inter-individual variability in DRF and may
      help us to better understand the structural mechanisms in the brain underlying
      dream recall.

PMID- 30206819
TI  - Predicting trait-like individual differences in fear of pain in the healthy state
      using gray matter volume.
AB  - Fear of pain (FOP) can be considered as a product of evolution from overstated
      negative interpretations of pain and sometimes may cause more damage than the
      actual pain itself. While trait-like measures of FOP have emerged as predictors
      for the inception and development of chronic pain, its neural underpinnings are
      not well understood. To investigate the relationship between gray matter volumes
      (GMV) and trait-like individual differences in FOP, we analyzed structural
      magnetic resonance imaging data in a sample of healthy young adults. Regression
      analysis results showed that individuals with higher FOP scores displayed higher
      GMV in brain regions important for the regulation of pain and fear. These brain
      areas include the pregenual anterior cingulate cortex (ACC), the anterior part of
      the dorsal ACC, the dorsomedial prefrontal cortex, and the adjacent pre
      supplementary motor area. Furthermore, cross-validation analysis confirmed that
      the identified regional GMV offered a reliable neural signature of trait-like
      FOP. Our findings shed more light on the neuroanatomical architecture of FOP in
      currently pain-free people, which may be helpful to guide early interventions to
      prevent FOP from becoming chronic.

PMID- 30206820
TI  - 72-Week Safety and Tolerability of Dimethyl Fumarate in Japanese Patients with
      Relapsing-remitting Multiple Sclerosis: Analysis of the Randomised, Double Blind,
      Placebo-Controlled, Phase III APEX Study and its Open-Label Extension.
AB  - INTRODUCTION: The long-term safety of dimethyl fumarate (DMF) in patients with
      relapsing-remitting multiple sclerosis (RRMS) has been studied in mainly
      Caucasian patients. The present interim analysis aimed to evaluate the 72-week
      safety of DMF in Japanese patients with RRMS. METHODS: Safety data of Japanese
      subjects enrolled in the 24-week randomised, double-blind, placebo-controlled
      APEX study (Part I) and its following open-label extension (Part II) were
      analysed at 72 weeks from the beginning of Part I. In Part I, subjects were
      randomised to DMF treatment or matching placebo while all subjects received DMF
      treatment during Part II. Adverse events (AEs) reported throughout the study
      period were recorded. RESULTS: Overall, 109 Japanese subjects completed 72 weeks
      of treatment. The incidence of AEs and serious AEs was 95% and 19%, respectively,
      in the DMF group compared with 84% and 18%, respectively, in the placebo group at
      24 weeks. Common AEs (at least 5%) reported with treatment included
      nasopharyngitis, flushing, hot flush, gastrointestinal events, pruritus, rash,
      headache, increased alanine aminotransferase (ALT) and aspartate aminotransferase
      (AST). AEs led to discontinuation of DMF in 5% of patients and included MS
      relapse, flushing, abdominal pain, liver disorder and increased ALT/AST. After an
      initial decrease from baseline of 17% in the DMF group at week 24, the mean
      lymphocyte counts stabilised and were maintained until week 72. No
      opportunistic/serious infections nor malignancies were reported with DMF
      treatment. The incidences of AEs, serious AEs, and discontinuation due to AEs
      were similar between the DMF and the placebo groups. CONCLUSION: The 72-week
      safety profile of DMF in Japanese patients with RRMS was consistent with previous
      studies that enrolled mostly Caucasian patients, with a lower incidence of
      flushing and related symptoms and a lower reduction in the lymphocyte count
      compared with previous reports. TRIAL REGISTRATION: ClinicalTrials.gov identifier
      NCT01838668. FUNDING: Biogen Japan Ltd.

PMID- 30206821
TI  - Predicting Responses to Pregabalin for Painful Diabetic Peripheral Neuropathy
      Based on Trajectory-Focused Patient Profiles Derived from the First 4 Weeks of
      Treatment.
AB  - INTRODUCTION: Prediction of final clinical outcomes based on early weeks of
      treatment can enable more effective patient care for chronic pain. Our goal was
      to predict, with at least 90% accuracy, 12- to 13-week outcomes for pregabalin
      treated painful diabetic peripheral neuropathy (pDPN) patients based on 4 weeks
      of pain and pain-related sleep interference data. METHODS: We utilized active
      treatment data from six placebo-controlled randomized controlled trials (n = 939)
      designed to evaluate efficacy of pregabalin for reducing pain in patients with
      pDPN. We implemented a three-step, trajectory-focused analytics approach based
      upon patient responses collected during the first 4 weeks using monotonicity,
      path length, frequency domain (FD), and k-nearest neighbor (kNN) methods. The
      first two steps were based on combinations of baseline pain, pain at 4 weeks,
      weekly monotonicity and path length during the first 4 weeks, and assignment of
      patients to one of four responder groups (based on presence/absence of 50% or 30%
      reduction from baseline pain at 4 and at 12/13 weeks). The third step included
      agreement between prediction of logistic regression of daily FD amplitudes and
      assignment made from kNN analyses. RESULTS: Step 1 correctly assigned 520/939
      patients from the six studies to a responder group using a 3-metric combination
      approach based on unique assignment to a 50% responder group. Step 2 (applied to
      the remaining 419 patients) predicted an additional 121 patients, using a blend
      of 50% and 30% responder thresholds. Step 3 (using a combination of FD and kNN
      analyses) predicted 204 of the remaining 298 patients using the 50% responder
      threshold. Our approach correctly predicted 90.0% of all patients. CONCLUSION: By
      correctly predicting 12- to 13-week responder outcomes with 90% accuracy based on
      responses from the first month of treatment, we demonstrated the value of
      trajectory measures in predicting pDPN patient response to pregabalin. TRIAL
      REGISTRATION: www.clinicaltrials.gov identifiers,
      NCT00156078/NCT00159679/NCT00143156/NCT00553475. FUNDING: Pfizer. Plain language
      summary available for this article.

PMID- 30206822
TI  - Medication Adherence and Discontinuation of Aripiprazole Once-Monthly 400 mg (AOM
      400) Versus Oral Antipsychotics in Patients with Schizophrenia or Bipolar I
      Disorder: A Real-World Study Using US Claims Data.
AB  - INTRODUCTION: Few studies have compared adherence between long-acting injectable
      antipsychotics, especially for newer agents like aripiprazole once-monthly 400 mg
      (AOM 400; aripiprazole monohydrate) and oral antipsychotics, in patients with
      schizophrenia or bipolar I disorder (BD-I) in a real-world setting. METHODS: Two
      separate retrospective cohort analyses using Truven MarketScan data from January
      1, 2012 to June 30, 2016 were conducted to compare medication adherence and
      discontinuation in patients with schizophrenia or BD-I who initiated treatment
      with AOM 400 vs. patients changed from one oral antipsychotic monotherapy to
      another. Adherence was defined as proportion of days covered (PDC) >= 0.80 in the
      year following the index date. Linear regression models examined the association
      between AOM 400 and oral antipsychotic cohorts and medication adherence. Kaplan
      Meier curves and Cox regression estimated time to and risk of discontinuation,
      while adjusting for baseline covariates. A sensitivity analysis was conducted
      using a combination of propensity score matching and exact matching to create
      matched cohorts. RESULTS: Final cohort sizes were as follows-Schizophrenia: AOM
      400 n = 408, oral antipsychotic n = 3361; BD-I: AOM 400 n = 413, oral
      antipsychotic n = 15,534. In patients with schizophrenia, adjusted mean PDC was
      higher in patients in the AOM 400 cohort vs. the oral antipsychotic cohort (0.57
      vs. 0.48 P < 0.001), and patients in the oral antipsychotic cohort had a higher
      risk of discontinuing treatment vs. the AOM 400 cohort (HR 1.45, 95% CI 1.29
      1.64). For patients with BD-I, adjusted mean PDC was higher for the AOM 400
      cohort (0.59 vs. 0.44, P < 0.001), and patients in the oral antipsychotic cohort
      had a higher risk of discontinuation (HR 1.71, 95% CI 1.53-1.92). CONCLUSIONS: In
      a real-word setting, AOM 400 resulted in a significantly higher percentage of
      patients with a PDC >= 0.80 and significantly longer time to treatment
      discontinuation compared to patients with schizophrenia or BD-I who received
      treatment with an oral antipsychotic. FUNDING: Otsuka Pharmaceutical Development
      and Commercialization, Inc. and Lundbeck.

PMID- 30206824
TI  - Efficacy of Topical Combination of 0.25% Finasteride and 3% Minoxidil Versus 3%
      Minoxidil Solution in Female Pattern Hair Loss: A Randomized, Double-Blind,
      Controlled Study.
AB  - BACKGROUND: The relationship between female pattern hair loss (FPHL) and
      androgenic hormones is not well established, but some evidence indicates oral
      finasteride may be efficacious in FPHL. Use of a topical formulation has been
      proposed to minimize unwanted effects. OBJECTIVES: Our objective was to compare
      the efficacy and safety of topical 0.25% finasteride combined with 3% minoxidil
      solution and 3% minoxidil solution as monotherapy in the treatment of FPHL.
      METHODS: This was a prospective, randomized, double-blind study in 30
      postmenopausal women with FPHL. Each participant was randomized to receive either
      topical 0.25% finasteride combined with topical 3% minoxidil or topical 3%
      minoxidil solution as monotherapy for 24 weeks. To determine efficacy, the hair
      density and diameter was measured and global photographic assessment was
      conducted at baseline and 8, 16, and 24 weeks. Side effects and serum
      dihydrotestosterone levels were also evaluated. RESULTS: By 24 weeks, hair
      density and diameter had increased in both groups, and finasteride/minoxidil was
      significantly superior to minoxidil solution in terms of hair diameter (p =
      0.039). No systemic side effects were reported. However, serum
      dihydrotestosterone levels in the finasteride/minoxidil group significantly
      decreased from baseline (p = 0.016). CONCLUSION: A topical combination of 0.25%
      finasteride and 3% minoxidil may be a promising option in the treatment of FPHL
      with an additional benefit of increasing hair diameter. Nevertheless, as it may
      be absorbed percutaneously, it should be reserved for postmenopausal women. TRIAL
      REGISTRATION: clinicaltrials.in.th; identifier TCTR20160912002.

PMID- 30206823
TI  - Does 'Strong Analgesic' Equal 'Strong Opioid'? Tapentadol and the Concept of 'u
      Load'.
AB  - INTRODUCTION: The distinct properties of the centrally-acting analgesic
      tapentadol derive from the combined contributions of an opioid component and a
      nonopioid component. However, the opioid component's relative contribution to
      analgesic and adverse effects has not previously been elucidated. Tapentadol's
      analgesic effect derives from the combined contribution of an opioid mechanism
      and a nonopioid mechanism, the extent of which can vary for different pains.
      Likewise, the interaction can vary for various adverse effects. Hence, the
      contribution of each mechanism to adverse effects can be different from the
      contribution to analgesia. We here estimate the percent contribution of each
      component of the mechanism of action to analgesia and to adverse effects. AREAS
      COVERED: Several approaches to in vitro and in vivo data to estimate the
      contribution of tapentadol's opioid component to analgesia and to the two
      important opioid adverse effects, respiratory depression and constipation. The
      results are then compared with clinical data. EXPERT OPINION: Traditional
      opioids, such as morphine, oxycodone, and others, produce their analgesic effects
      primarily through a single mechanism-the activation of u-opioid receptors (MOR).
      Therefore, the contribution of the opioid component to adverse effects is 100%.
      In contrast, the newer strong analgesic tapentadol produces its analgesic effect
      via two separate and complementary analgesic mechanisms, only one of which is u
      opioid. We applied standard drug-receptor theory and novel techniques to in vitro
      and in vivo data to estimate by several different ways the MU-load of tapentadol
      (the % contribution of the opioid component to the adverse effect magnitude
      relative to a pure/classical u-opioid at equianalgesia) in respiratory depression
      and constipation, and we compared the results to clinical evidence. The estimate
      is remarkably consistent over the various approaches and indicates that the MU
      load of tapentadol is <= 40% (relative to pure MOR agonists, which have, by
      definition, a u-load of 100%). FUNDING: Grunenthal GmbH.

PMID- 30206825
TI  - Correction to: Can We Accurately Predict Cost Effectiveness Without Access to
      Overall Survival Data? The Case Study of Nivolumab in Combination with Ipilimumab
      for the Treatment of Patients with Advanced Melanoma in England.
AB  - The second Key Point for Decision Makers, which reads.

PMID- 30206829
TI  - Distribution of beryllium-7 (7Be) in the Black Sea in the summer of 2016.
AB  - The spatial distribution of 7Be activity in the surface layer of the Black Sea
      was studied using the data of field observations made during the 87th cruise of
      R/V Professor Vodyanitskii. Activity of 7Be varied spatially from 4.6 to 9.5 Bq m
      3 (mean 7.5 +/- 1.3 Bq m-3) where about 9% was found on suspended matter. The
      minimum values of activity were typical for samples taken in the shelf waters and
      the maximum-offshore. The influence of different factors on 7Be activity was
      analyzed. It was revealed that variation of both 7Be wet deposition on the sea
      surface and concentration of suspended matter were the most significant for
      spatiotemporal variability of 7Be activity in seawater during the study period.
      The estimates of 7Be distribution coefficient between dissolved and particulate
      forms were obtained. This coefficient varied from 1.5.105 to 2.4.105 L kg-1,
      averaged (1.9 +/- 0.3).105 L kg-1.

PMID- 30206827
TI  - Characterization of bacterial and microbial eukaryotic communities associated
      with an ephemeral hypoxia event in Taihu Lake, a shallow eutrophic Chinese lake.
AB  - While the important roles of microbial communities in oceanic hypoxic zones were
      beginning to be understood, little is known about microbial community associated
      with this phenomenon in shallow lakes. To address this deficit, both the
      bacterial and microbial eukaryotic communities of an ephemeral hypoxic area of
      Taihu Lake were characterized. The hypoxia provided nutritional niches for
      various bacteria, which results in high abundance and diversity. Specific
      bacterial groups, such as vadinBC27 subgroup of Bacteroidetes, Burkholderiales,
      Rhodocyclales, Pseudomonas, and Parcubacteria, were dominated in hypoxic sites
      and relevant to the fermentation, denitrification, nitrification, and sulfur
      metabolism. Conversely, most of microbial eukaryotes disappeared along with the
      decline of DO. An unexpected dominance of fungi was observed during hypoxia,
      which partly explained by the accumulation of toxic algae. Mucor was the single
      dominant genus in the hypoxic zone. We proposed that this group might cooperate
      with bacterial communities in the anaerobic degradation of algal biomass and
      woody materials. Generally, the hypoxic microbiome in shallow lakes is mainly
      involved in fermentative metabolism depending on phytodetritus and is potentially
      influenced by terrestrial sources. This study provided new insights into the
      unique microbiome in short-term hypoxia in shallow lakes and lays the foundation
      for studies that will enhance our understanding of the microbial players
      associated with hypoxia and their adaption strategy on the global scale.

PMID- 30206826
TI  - Does Structured Exercise Improve Cognitive Impairment in People with Mild to
      Moderate Dementia? A Cost-Effectiveness Analysis from a Confirmatory Randomised
      Controlled Trial: The Dementia and Physical Activity (DAPA) Trial.
AB  - BACKGROUND: Previous studies suggest that physical exercise could slow dementia
      progression. However, evidence for the cost effectiveness of structured exercise
      is conflicting and based on small trials. OBJECTIVES: The objective of this study
      was to compare the cost effectiveness of a tailored, structured, moderate- to
      high-intensity exercise programme versus usual care in people with mild to
      moderate dementia. METHODS: An economic evaluation was conducted from the UK
      National Health Service and personal social services perspective, based on data
      from a large randomised controlled trial. The primary clinical outcome was the
      participant reported ADAS-Cog (Alzheimer's Disease Assessment Scale-Cognitive
      Subscale) at 12 months. Costs (L; 2014-2015 prices) were collected prospectively
      over a 12-month follow-up period. A bivariate regression of costs and quality
      adjusted life-years (QALYs), with multiple imputation of missing data, was
      conducted with the view to estimating the incremental cost per QALY gained and
      the incremental net monetary benefit (INMB) associated with the exercise
      programme plus usual care versus usual care. Sensitivity analyses were undertaken
      to assess the impact of uncertainty surrounding aspects of the economic
      evaluation, and pre-specified subgroup analyses explored heterogeneity in the
      cost-effectiveness results. RESULTS: Participants (n = 494) were randomised to
      exercise plus usual care or usual care only. By 12 months the mean ADAS-Cog score
      had worsened slightly to 25.2 (standard deviation [SD] 12.3) in the exercise arm
      and 23.8 (SD 10.4) in the usual care: difference - 1.4, 95% confidence interval
      (CI) - 2.6 to - 0.2 (p = 0.03). The mean (standard error [SE]) costs over 12
      months for experimental versus control was L5945 (US$7856) versus L4597
      (US$6574), respectively; (difference: L1347 [$1926]; p = 0.0426). Mean (SE) QALY
      estimates were 0.787 (0.012) versus 0.826 (0.019), respectively (p = 0.090). The
      probability that the exercise programme is cost effective was < 1% across cost
      effectiveness thresholds. INMBs ranged between -L2601 (US$3719) and L2158
      (US$3086) at cost-effectiveness thresholds between L15,000 (US$21,450) and
      L30,000 (US$42,900) per QALY. The cost-effectiveness results remained robust to
      several sensitivity and subgroup analyses. CONCLUSIONS: Building on the clinical
      results of the trial, which showed that the structured exercise programme
      evaluated does not slow cognitive impairment in people with mild to moderate
      dementia, this economic evaluation shows that the programme is not cost
      effective.

PMID- 30206828
TI  - Micronucleus frequency is correlated with antioxidant enzyme levels in workers
      occupationally exposed to pesticides.
AB  - Oxidative stress can cause DNA damage leading to nuclear anomalies such as
      micronuclei (MN). Antioxidant enzymes involved in protection against
      intracellular oxidative stress include glutathione peroxidase (GPx), glutathione
      reductase (GR), superoxide dismutase (SOD), and catalase (CAT). Pesticide
      exposure induces oxidative stress and alters antioxidant defense mechanisms,
      including detoxification and scavenger enzymes. The aim of this study was to
      evaluate MN frequency in workers occupationally exposed to pesticides and their
      relationship with antioxidant enzyme activities. A cross-sectional study was
      conducted in 201 individuals, some of whom were dedicated to the spraying of
      pesticides. The cytokinesis-block micronucleus (CBMN) assay was conducted, and
      the activities of GPx, GR, SOD, and CAT were determined. The geometric mean (GM)
      of MN was 5.4 (1-26 MN). The GM for the antioxidant enzymes was 198.68 U/mL for
      GPx, 38.96 U/g Hb for GR, 94.78 U/mL for SOD, and 69.77 U/g Hb for CAT. There was
      a lower MN frequency in males than that in females, and a higher nuclear index.
      In addition, age affected MN frequency. There was a negative correlation between
      MN frequency and GPx activity, but a positive one between MN frequency and GR
      activity. These findings suggest the involvement of GPx in MN frequency.

PMID- 30206830
TI  - Role of sorption energy and chemisorption in batch methylene blue and Cu2+
      adsorption by novel thuja cone carbon in binary component system: linear and
      nonlinear modeling.
AB  - Functionalized thuja cone carbon (FTCC) was synthesized thermochemically. It was
      carried out by carbonization (250  degrees C) and activation (320  degrees C),
      followed by surface functionalization in 0.5 M HAN (HNO and HCl3) mixture and
      subsequent heating in H2SO4 (95%) at 90  degrees C. This was used for methylene
      blue (MB) adsorption in single component system (SCS) and binary component system
      (BCS) with Cu2+. Maximum adsorption capacity of MB (83.4 mg/g) was achieved at pH
      10 at 100 mg/L of adsorbate solution. MB and Cu2+ adsorption onto FTCC obeyed
      pseudo-second-order model kinetics. Spontaneous and endothermic MB adsorption was
      noticed with negative Gibbs free energy change (- 6.34, - 9.20, and - 13.78
      kJ/mol) and positive enthalpy change (133.91 kJ/mol). At low concentrations, Cu2+
      adsorption increased by 14 mg/g with least reduction of MB adsorption (< 4 mg/g)
      in BCS. Isotherm models (Langmuir, Freundlich, Temkin, and Dubinin-Radushkevich)
      support the increase in Cu2+ adsorption in BCS. The sorption heat of MB shifted
      from 165.16 kJ/mol (SCS) to 150.85 kJ/mol in BCS (Temkin) and from 57.74 kJ/mol
      (SCS) to 50.50 kJ/mol in BCS (D-R), which supports the lower MB uptake in BCS due
      to decrease in sorption energy. The sorption heat of Cu2+ is increased (148.43
      kJ/mol) in the BCS than SCS (155.36 kJ/mol), which makes the equal distribution
      of increased bonding energies; therefore, FTCC surface sites increased the Cu2+
      uptake in the BCS. Desorption studies concluded the reusability of FTCC by 75%
      and 79% for MB and Cu2+ adsorption respectively. This study recommends to
      determine the best fit of isotherm and kinetic models to adsorption data by
      linear as well as nonlinear regression fit.

PMID- 30206831
TI  - Uptake effects of toxic heavy metals from growth soils into jujube and persimmon
      of China.
AB  - Compared with other agricultural plants, information about uptake effects of
      toxic heavy metals from growth soils into persimmon and jujube are scarce. In
      this study, the single and comprehensive uptake effects of five toxic heavy
      metals (Pb, As, Cd, Cr, and Hg) between the two fruits and their growth soils
      were investigated. The results showed that the average concentrations of heavy
      metals in the two fruits were found to be 30 (Pb), 6.6 (As), 2.3 (Cd), 38 (Cr),
      and 0.33 (Hg) MUg/kg, respectively. The average concentrations of heavy metals in
      their growth soils were 26.31 (Pb), 9.63 (As), 0.12 (Cd), 57.6 (Cr), and 0.049
      (Hg) mg/kg, respectively. An uptake effect was observed for the two fruits. The
      values of Nemerow pollution index (NPI) in the two fruits and their growth soils
      were 0.10 and 0.55, respectively. The average bioconcentration factor (BCF)
      values of Pb, As, Cd, Cr, and Hg in the two fruits were 0.0012, 0.00075, 0.021,
      0.00077, and 0.012, respectively. Based on the residue levels of toxic heavy
      metals in the growth soils and soil parameters, the prediction models for NPI and
      BCF were established, with the adjusted regression coefficients of 0.65 (NPI) and
      0.81 (BCF). The contribution rates of different soil parameters to NPI were 21.7%
      (OC), 16.1% (Pb), 17.1% (Cr), 19.8% (Cd), and 25.4% (As), respectively. The
      contribution rates of different soil parameters to BCF were 10.2% (OC), 9.4%
      (Cr), and 80.4% (Cd), respectively.

PMID- 30206833
TI  - The role of renewable and non-renewable energy consumption in CO2 emissions: a
      disaggregate analysis of Pakistan.
AB  - The energy sector has become the largest contributor to greenhouse gas (GHG)
      emissions. Among these GHG emissions, most threatening is CO2 emission which
      comes from the consumption of fossil fuels. This empirical work analyzes the
      roles of renewable energy consumption and non-renewable energy consumption in CO2
      emissions in Pakistan. The empirical evidence is based on an auto-regressive
      distributive lag (ARDL) model of data from 1970 to 2016. The disaggregate
      analysis reveals that renewable energy consumption has an insignificant impact on
      CO2 emission in Pakistan and that, in the non-renewable energy model, natural gas
      and coal are the main contributors to the level of pollution in Pakistan.
      Economic growth positively contributes to CO2 emission in the renewable energy
      model but not in the non-renewable energy model. Policies that emphasize the
      contribution of renewable energy to economic growth and that add more clean
      energy into the energy mix are suggested.

PMID- 30206832
TI  - Different pathways of nitrogen and phosphorus regeneration mediated by
      extracellular enzymes in temperate lakes under various trophic state.
AB  - Several Italian and Chinese temperate lakes with soluble reactive phosphorus
      concentrations < 0.015 mg L-1 were studied to estimate nitrogen and phosphorus
      regeneration mediated by microbial decomposition and possible different
      mechanisms driven by prevailing oligo- or eutrophic conditions. Leucine
      aminopeptidase (LAP), beta-glucosidase (GLU) and alkaline phosphatase (AP),
      algal, and bacterial biomass were related to trophic and environmental variables.
      In the eutrophic lakes, high algal and particulate organic carbon concentrations
      stimulated bacterial respiration (> 20 MUg C L-1 h-1) and could favor the release
      of inorganic phosphorus. High extracellular enzyme activities and phosphorus
      solubilizing bacteria abundance in sediments accelerated nutrient regeneration.
      In these conditions, the positive GLU-AP relationship suggested the coupling of
      carbon and phosphorus regeneration; an efficient phosphorus regeneration and high
      nitrogen levels (up to 0.067 and 0.059 mg L-1 NH4 and NO3 in Italy; 0.631 and
      1.496 mg L-1 NH4 and NO3 in China) led to chlorophyll a peaks of 14.9 and 258.4
      MUg L-1 in Italy and China, respectively, and a typical algal composition.
      Conversely, in the oligo-mesotrophic lakes, very low nitrogen levels (in Italy,
      0.001 and 0.005 mg L-1 NH4 and NO3, respectively, versus 0.053 and 0.371 mg L-1
      in China) induced high LAP, while low phosphorus (33.6 and 46.3 MUg L-1 total P
      in Italy and China, respectively) led to high AP. In these lakes, nitrogen and
      phosphorus regeneration were coupled, as shown by positive LAP-AP relationship;
      however, the nutrient demand could not be completely met without the supply from
      sediments, due to low enzymatic activity and phosphorus solubilizing bacteria
      found in this compartment.

PMID- 30206834
TI  - Markov-switching vector autoregressive neural networks and sensitivity analysis
      of environment, economic growth and petrol prices.
AB  - The paper aims at evaluating the nonlinear and complex relations between CO2
      emissions, economic development, and petrol prices to obtain new insights
      regarding the shape of the environmental Kuznets curve (EKC) in the USA and in
      the UK in addition to introducing a newly proposed nonlinear approach. Within
      this respect, the paper has three purposes: the first one is to combine the
      multilayer perceptron neural networks (MLP) with Markov-switching vector
      autoregressive (MS-VAR) type nonlinear models to obtain the MS-VAR-MLP model. The
      second is to utilize one of the largest datasets in the literature covering the
      1871-2016 period, a long span of data starting from the late eighteenth century.
      Since the emission, economic development, and petrol price relation is subject to
      nonlinearity and trajectory changes due to many historical events, the
      development of the MS-VAR-MLP model is a necessity to contribute to the ongoing
      debate regarding the shape of the EKC curve and the stability of the relation.
      The third purpose is to develop the MS-VAR-MLP-based regime-dependent sensitivity
      analysis, which eases the visual interpretation of the nonlinear causal
      relationships, which are allowed to have asymmetric interactions in different
      phases of the expansionary and recessionary periods of the business cycles. Our
      results provide clear deviations from the findings in the literature: (i) the
      shape of the EKC curve cannot be assumed to be stable and is subject to regime
      dependency, nonlinearity, and magnitude dependency; (ii) the forecast results
      suggest that incorporation of regime switching and neural networks provide
      significant improvement over the MS-VAR counterpart; and (iii) for both USA and
      UK and for the 1871-2016 period, the positive impacts of economic growth on
      emissions cannot be rejected for the majority of the phases of the business
      cycles; however, the magnitude of this effect is at various degrees. In addition,
      the incorporation of petrol price provides significant findings considering its
      effects on emission and economic growth rates. The analysis suggest clear
      deviations from the expected shape of the EKC curve and puts forth the necessity
      to utilize more complex empirical methodologies to evaluate the EKC since the
      emissions-economic development relation is more complex than it was assumed.
      Following these findings, several policy recommendations are provided. Lastly,
      the proposed MS-VAR-MLP methodology is compared with the MS-VAR model and various
      advantages and disadvantages are enumerated.

PMID- 30206835
TI  - ?

PMID- 30206837
TI  - ?

PMID- 30206838
TI  - ?

PMID- 30206836
TI  - ?

PMID- 30206839
TI  - ?

PMID- 30206840
TI  - ?

PMID- 30206841
TI  - ?

PMID- 30206842
TI  - ?

PMID- 30206843
TI  - [Therapy of diabetes and obesity].

PMID- 30206844
TI  - ?

PMID- 30206845
TI  - [Chronic constipation].

PMID- 30206846
TI  - [The speechless patient].

PMID- 30206847
TI  - [The crying patient].

PMID- 30206849
TI  - [The aggressive patient].

PMID- 30206848
TI  - [Patients with tics].

PMID- 30206850
TI  - ?

PMID- 30206852
TI  - ?

PMID- 30206851
TI  - ?

PMID- 30206853
TI  - ?

PMID- 30206854
TI  - ?

PMID- 30206855
TI  - ?

PMID- 30206856
TI  - ?

PMID- 30206858
TI  - ?

PMID- 30206857
TI  - ?

PMID- 30206860
TI  - ?

PMID- 30206859
TI  - ?

PMID- 30206861
TI  - ?

PMID- 30206863
TI  - ?

PMID- 30206862
TI  - ?

PMID- 30206864
TI  - ?

PMID- 30206866
TI  - ?

PMID- 30206865
TI  - ?

PMID- 30206867
TI  - ?

PMID- 30206868
TI  - ?

PMID- 30206869
TI  - ?

PMID- 30206870
TI  - ?

PMID- 30206871
TI  - ?

PMID- 30206872
TI  - ?

PMID- 30206873
TI  - ?

PMID- 30206874
TI  - ?

PMID- 30206875
TI  - ?

PMID- 30206876
TI  - ?

PMID- 30206877
TI  - ?

PMID- 30206878
TI  - ?

PMID- 30206879
TI  - ?

PMID- 30206880
TI  - ?

PMID- 30206881
TI  - ?

PMID- 30206883
TI  - ?

PMID- 30206882
TI  - ?

PMID- 30206884
TI  - ?

PMID- 30206885
TI  - ?

PMID- 30206886
TI  - ?

PMID- 30206887
TI  - ?

PMID- 30206889
TI  - ?

PMID- 30206888
TI  - ?

PMID- 30206890
TI  - ?

PMID- 30206893
TI  - ?

PMID- 30206892
TI  - ?

PMID- 30206894
TI  - ?

PMID- 30206895
TI  - ?

PMID- 30206896
TI  - [Knee pain - symptoms, diagnosis and therapy of osteoarthritis].

PMID- 30206897
TI  - Pharmacokinetic and pharmacodynamic studies of etodolac loaded vesicular gels on
      rats by transdermal delivery.
AB  - BACKGROUND: The present study includes the development of liposomal and ethosomal
      gels for transdermal delivery to overcome the side effects associated with oral
      route. METHODS: The liposomes and ethosomes were prepared by 32 factorial design
      using film hydration and cold methods, respectively. Different concentrations of
      liposomal (ETO-LG) and ethosomal (ETO-EG) gels were prepared at 1%, 2 and 3%
      (w/v) using carbopol 940 NF. 1%w/v ETO-LG & ETO-EG were optimized upon
      rheological studies of prepared gels. The optimized gels were further
      characterized for various physicochemical properties and biophysical studies
      using FTIR, pharmacokinetic (PK) and pharmacodynamic (PD) studies. The
      pharmacodynamic activity was performed using carrageenan paw oedema model. The
      prepared vesicular gels were compared with 45% v/v ethanolic ETO-solution and
      marketed gel PROXYM(r) in all the characteristic parameters. RESULTS: The
      pharmacokinetic study reveals that the half life of etodolac in ETO-EG was 1.56
      folds whereas ETO-LG showed 1.31 folds higher than PROXYM(r). The mean residence
      time (MRT) of etodolac in ETO-EG and ETO-LG is increased in 1.57 and 1.25 folds,
      respectively, when compared to PROXYM(r). The ETO-EG showed higher percentage
      reduction in oedema (81.67%) compared to other test products. CONCLUSION: The
      pharmacokinetic and pharmacodynamic studies indicated that the vesicular gels
      show better results compared to PROXYM(r). The correlation coefficient value
      between PK and PD was found to be 0.9635. Graphical abstract ?.

PMID- 30206898
TI  - A review of quality of life (QOL) assessments and indicators: Towards a "QOL
      Climate" assessment framework.
AB  - Quality of life (QOL), although a complex and amorphous concept, is a term that
      warrants attention, especially in discussions on issues that touch on the impacts
      of climate change and variability. Based on the principles of RepOrting standards
      for Systematic Evidence Synthesis, we present a systematic review aimed at
      gaining insights into the conceptualization and methodological construct of
      previous studies regarding QOL and QOL-related indexes. We find that (i) QOL
      assessments vary in terms of conceptual foundations, dimensions, indicators, and
      units of analysis, (ii) social indicators are consistently used across
      assessments, (iii) most assessments consider indicators that pertain to the
      livability of the environment, and (iv) QOL can be based on objective indicators
      and/or subjective well-being, and on a composite index or unaggregated dimensions
      and indicators. However, we also find that QOL assessments remain poorly
      connected with climate-related issues, an important research gap. Our proposed
      "QOL-Climate" assessment framework, designed to capture the social-ecological
      impacts of climate change and variability, can potentially help fill this gap.

PMID- 30206899
TI  - Transformative capacity and local action for urban sustainability.
AB  - There is a consensus about the strategic importance of cities and urban areas for
      achieving a global transformation towards sustainability. While there is mounting
      interest in the types of qualities that increase the capacity of urban systems to
      attain deep transformations, empirical evidence about the extent to which
      existing institutional and material systems exhibit transformative capacity is
      lacking. This paper thereby seeks to determine the extent to which sustainability
      initiatives led by local governments and their partners reflect the various
      components that the literature claims can influence the emergence of
      transformative capacity as a systemic property of urban settings. Using an
      evaluative framework consisting of ten components of transformative capacity and
      associated indicators, the specific objective is to identify patterns in these
      initiatives regarding the presence of individual components of transformative
      capacity and their interrelations with other components. The analysis of 400
      sustainability initiatives reveals thin evidence of transformative capacity. When
      detected, evidence of transformative capacity tended to emerge in relation to
      wider processes of institutional- and social-learning and initiatives that linked
      outcomes to a city-wide vision of planning and development. However, instances of
      such initiatives were rare. This widespread lack of evidence for transformative
      capacity raises concerns that this set of attributes normalised in the literature
      is in fact rarely found in sustainability action on the ground.

PMID- 30206900
TI  - Climate change in Northern Russia through the prism of public perception.
AB  - This article fills a major hole in the Western literature on climate change
      perceptions by reporting detailed data from Russia. While Northern Russia
      demonstrates high rates of climate change, regional adaptation policies are yet
      to be established. Complicating the problem, how the Russian public perceives
      climate change remains poorly known. This study synthesizes data from
      observations, modeling, and sociological surveys, and gives insight into the
      public perceptions of current and projected future changes in climate. Results
      indicate that, similar to what is found in the Western context, unusual weather
      patterns and single extreme events have a deeper impact than long-term climate
      change on public perceptions. The majority of the population considers climate
      and environmental changes locally, does not associate them with global drivers,
      and is not prepared to act on them. Accordingly, even the best designed climate
      policies cannot be implemented in Northern Russia, because there is no public
      demand for them. To address this situation, climate scientists should work to
      educate members of the public about basic scientific concepts so that they begin
      to demand better climate policies.

PMID- 30206901
TI  - Neural Regulation of Paternal Behavior in Mammals: Sensory, Neuroendocrine, and
      Experiential Influences on the Paternal Brain.
AB  - Across the animal kingdom, parents in many species devote extraordinary effort
      toward caring for offspring, often risking their lives and exhausting limited
      resources. Understanding how the brain orchestrates parental care, biasing effort
      over the many competing demands, is an important topic in social neuroscience. In
      mammals, maternal care is necessary for offspring survival and is largely
      mediated by changes in hormones and neuropeptides that fluctuate massively during
      pregnancy, parturition, and lactation (e.g., progesterone, estradiol, oxytocin,
      and prolactin). In the relatively small number of mammalian species in which
      parental care by fathers enhances offspring survival and development, males also
      undergo endocrine changes concurrent with birth of their offspring, but on a
      smaller scale than females. Thus, fathers additionally rely on sensory signals
      from their mates, environment, and/or offspring to orchestrate paternal behavior.
      Males can engage in a variety of infant-directed behaviors that range from
      infanticide to avoidance to care; in many species, males can display all three
      behaviors in their lifetime. The neural plasticity that underlies such stark
      changes in behavior is not well understood. In this chapter we summarize current
      data on the neural circuitry that has been proposed to underlie paternal care in
      mammals, as well as sensory, neuroendocrine, and experiential influences on
      paternal behavior and on the underlying circuitry. We highlight some of the gaps
      in our current knowledge of this system and propose future directions that will
      enable the development of a more comprehensive understanding of the proximate
      control of parenting by fathers.

PMID- 30206902
TI  - Blood Glucose Monitoring and Its Determinants in Diabetic Patients: A Cross
      Sectional Study in Shandong, China.
AB  - INTRODUCTION: The aim of this study was to explore the status of blood glucose
      monitoring and its determinants in diabetic patients in Shandong Province, China.
      METHODS: This was a cross-sectional survey conducted from 31 August to 12 October
      12, in Shandong Province. A multi-stage stratified cluster sampling method was
      used to select participants. A total of 2183 diabetic patients were included in
      the analysis. Frequencies and proportions were used to describe the data, and
      multiple binary logistic regressions were performed to determine factors
      associated with blood glucose monitoring. RESULTS: Of the participants, 51.4%
      tested their blood glucose level more than once a month. The multivariate
      logistic regression model showed that seven variables were significantly
      associated with the frequency of blood glucose monitoring: education level,
      residence, household income, self-reported health, physical examination, anti
      diabetic drug or insulin injection, and comorbidity. CONCLUSIONS: The level of
      blood glucose monitoring among diabetic patients in Shandong Province is low.
      Based on these results we recommend that the cost of blood glucose monitoring by
      professionals in laboratories be reimbursed or at least reduced and that diabetic
      patients be encouraged to undergo regular physical examinations.

PMID- 30206904
TI  - Association of Vitamin D and Parathyroid Hormone with Insulin Sensitivity, Beta
      Cell Function and Gestational Diabetes in Pregnancy: A Cross-Sectional,
      Observational Study.
AB  - INTRODUCTION: Vitamin D (25OHD) and parathyroid hormone (PTH) are associated with
      dysglycemia, and we investigated them in gestational diabetes mellitus (GDM).
      METHODS: In this cross-sectional, observational study, we included 75 pregnant
      women between 24 and 28 weeks of gestation. A fasting venous sample was collected
      for plasma glucose (FPG), insulin, PTH and 25OHD. Glucose and insulin samples
      were collected hourly after 75 g glucose load for 2 h. Insulin sensitivity was
      estimated by the Matsuda index (MI) and beta cell function by the insulin
      secretion sensitivity index (ISSI-2). The subjects were stratified into three
      groups and tertiles according to the 25OHD and PTH, respectively. Appropriate
      statistical tests were used to compare the MI, ISSI-2 and GDM among the groups.
      RESULTS: GDM was seen in 14/75, and of these patients, 2 were 25OHD deficient, 7
      insufficient and 5 had sufficient 25OHD. MI and ISSI-2, though not correlated
      with the 25OHD, decreased from the lower to higher PTH tertile (P < 0.001). FPG,
      AUCgluc (area under the curve glucose) and prevalence of GDM increased from the
      lower to higher PTH tertile (P < 0.001). CONCLUSION: Increased PTH was associated
      with decreased insulin sensitivity, beta cell function and GDM in pregnancy,
      irrespective of the underlying 25OHD level.

PMID- 30206906
TI  - SMFM 2018 Archive: Prematurity-Part 3 (Podcast).

PMID- 30206905
TI  - Risk factors for conversion to snare resection during colorectal endoscopic
      submucosal dissection in an expert Western center.
AB  - BACKGROUND:  There are limited data regarding the risk factors and consequences
      of conversion to endoscopic mucosal resection (rescue EMR) during colorectal
      endoscopic submucosal dissection (ESD) in Western centers. METHODS:  This was a
      retrospective analysis of a prospectively collected database, from which 225
      consecutive ESDs performed between 2013 and 2017 were selected. Of the included
      patients, 39 (18.6 %) required rescue EMR. Pre- and per-procedure characteristics
      were evaluated to determine the features associated with the need for rescue EMR.
      Outcomes and complications were also assessed. RESULTS:  210 patients were
      included, with median tumor size of 40 mm (range 20 - 110) and most tumors being
      in a non-rectal location (66.2 %). When compared with full ESD, rescue EMR was
      significantly associated with lower rates of en bloc resection (43.6 % vs. 100 %)
      and complete resection (R0 status; 28.2 % vs. 88.9 %), and with a higher rate of
      recurrence (5.1 % vs. 0 %) and more need for surgery (15.4 % vs. 3.5 %). In
      multivariable analysis, non-lifting (adjusted odds ratio [ORa] 3.06, 95 %
      confidence interval [CI] 1.23 - 7.66; P = 0.02), nongranular-type laterally
      spreading tumor (LST-NG; ORa 2.56, 95 %CI 1.10 - 5.99; P = 0.03), and difficult
      retroflexion (OR 3.22, 95 %CI 1.01 - 10.28; P = 0.049) were independent risk
      factors associated with conversion to rescue EMR, while tumor size and location
      were not. CONCLUSIONS:  During ESD, the presence of poor lifting, LST-NG
      morphology, and a difficult retroflexed approach were factors associated with the
      need to convert to rescue EMR. Conversion to rescue EMR remains a valuable
      strategy.

PMID- 30206903
TI  - Comprehensive Evaluation of Combination Therapy with Basal Insulin and Either
      Lixisenatide or Vildagliptin in Japanese Patients with Type 2 Diabetes: A
      Randomized, Open-Label, Parallel-Group, Multicenter Study.
AB  - INTRODUCTION: We comprehensively evaluated the effects of combination therapy
      with insulin glargine and the incretin-based drugs lixisenatide or vildagliptin
      in Japanese patients with type 2 diabetes. METHODS: In this 12-week, randomized,
      open-label, parallel-group, multicenter study (GLP-ONE Kobe), the incretin-based
      drug sitagliptin was randomly switched to lixisenatide (20 MUg/day, n = 18) or
      vildagliptin (100 mg/day, n = 20) in patients with inadequate glycemic control
      despite combination therapy with insulin glargine and sitagliptin. The dose of
      insulin glargine was titrated after the switch to maintain fasting blood glucose
      at approximately 110 mg/dL. The primary end points of the study were the change
      in glycosylated hemoglobin (HbA1c) level between before and 12 weeks after the
      treatment switch, the proportion of patients achieving an HbA1c level below 7.0%,
      and the postprandial increase in glucose concentration as assessed by self
      monitoring of blood glucose. RESULTS: The change in HbA1c level from baseline to
      12 weeks did not differ significantly between the lixisenatide and vildagliptin
      groups (- 0.6 +/- 0.7% and - 0.6 +/- 1.2%, respectively, P = 0.920). Neither the
      proportion of patients achieving an HbA1c level below 7.0% nor the postprandial
      increase in glucose concentration was different between two groups. Body weight
      and serum low density lipoprotein (LDL) cholesterol level decreased significantly
      in the lixisenatide and vildagliptin groups, respectively. Both drugs were
      associated with mild gastrointestinal symptoms but not with severe hypoglycemia.
      Vildagliptin was associated with elevation of serum aspartate transaminase.
      Treatment satisfaction as assessed with the Diabetes Treatment Satisfaction
      Questionnaire did not differ significantly between the two groups. CONCLUSION:
      The combinations of basal insulin and either lixisenatide or vildagliptin have
      similar efficacies with regard to improvement of glycemic control. TRIAL
      REGISTRATION: This trial has been registered with UMIN (No. 000010769).

PMID- 30206907
TI  - Nanotechnological Approach to Increase the Antioxidant and Cytotoxic Efficacy of
      Crocin and Crocetin.
AB  - Crocin and crocetin are two interesting constituents of saffron (Crocus sativus)
      that possess important biological activities. Their use as therapeutic agents is
      strongly compromised by a scarce stability, poor absorption, and low
      bioavailability. Therefore, to improve these unfavorable features, the aim of the
      present work has been to apply a nanotechnological approach based on the
      formulation of solid lipid nanoparticles containing crocin and crocetin. Solid
      lipid nanoparticles were formulated according to crocin and crocetin chemical
      properties, using a variation of the quasi-emulsion solvent diffusion method to
      formulate crocin-solid lipid nanoparticles, while crocetin-solid lipid
      nanoparticles were prepared following the solvent diffusion method. Morphology
      and dimensional distribution of solid lipid nanoparticles have been characterized
      by differential scanning calorimetry and photon correlation spectroscopy,
      respectively, while the effect of drug incorporation versus time has been studied
      by Turbiscan technology. In order to verify the role of the nanotechnological
      approach on the biological activities of crocin and crocetin, the antioxidant and
      antiproliferative effects of these carotenoids once incorporated in lipid
      nanoparticles have been evaluated. For this aim, the oxygen radical absorbance
      capacity assay and the MTT test were used, respectively.The results pointed out
      the formulation of nanometric dispersions endowed with high homogeneity and
      stability, with an encapsulation efficiency ranging from 80 (crocetin-solid lipid
      nanoparticles) to 94% (crocin-crocetin). The oxygen radical absorbance capacity
      assay evidenced an interesting and prolonged antioxidant activity of crocin and
      crocetin once encapsulated in solid lipid nanoparticles, while the
      nanoencapsulation strategy showed a different mechanism in ameliorating the
      cytotoxic effect of these two substances.

PMID- 30206908
TI  - Video Tutorials Increase Precision in Minimally Invasive Surgery Training - a
      Prospective Randomised Trial and Follow-up Study.
AB  - BACKGROUND: Simulation-based practice has become increasingly important in
      minimally invasive surgery (MIS) training. Nevertheless, personnel resources for
      demonstration and mentoring simulation-based practice are limited. Video
      tutorials could be a useful tool to overcome this dilemma. However, the effect of
      video tutorials on MIS training and improvement of MIS skills is unclear.
      METHODS: A prospective randomised trial (n = 24 MIS novices) was conducted. A
      video-trainer with three different tasks (#1 - 3) was used for standardised goal
      directed MIS training. The subjects were randomised to two groups with standard
      instructional videos (group A, n = 12) versus comprehensive video tutorials for
      each training task watched at specific times of repetition (group B, n = 12).
      Performance was analysed using the MISTELS score. At the beginning and following
      the curriculum, an MIS cholecystectomy (CHE) was performed on a porcine organ
      model and analysed using the GOALS score. After 18 weeks, participants performed
      10 repetitions of tasks #1 - 3 for follow-up analysis. RESULTS: More participants
      completed tasks #1 and #2 in group B (83.3 and 75%) than in group A (66.7 and
      50%, ns). For task #2, there was a significant improvement in precision in group
      B (p < 0.001). For the entire cohort, the GOALS-Scores were 12.9 before and 18.9
      after the curriculum (p < 0.001), with no significant difference between groups.
      Upon follow-up, 84.2% (task#1), 26.3% (task#2) and 100% (task#3) of MIS novices
      were able to reach the defined goals (A vs. B ns). There was a trend for a better
      MISTELS score in group B upon follow-up. CONCLUSIONS: Standardised comprehensive
      video tutorials watched frequently throughout practice can significantly improve
      precision in MIC training. This aspect should be incorporated in MIS training.

PMID- 30206909
TI  - [The Impact of Supra- and Infracolic Reconstruction on Delayed Gastric Emptying
      Following Pancreatoduodenectomy].
AB  - BACKGROUND: Delayed gastric emptying (DGE) is the most frequent complication
      following pancreatoduodenectomy. While antecolic and retrocolic reconstruction
      does not influence the occurrence of DGE, infracolic reconstruction might
      alleviate DGE due to the vertical position of the distal stomach compared to
      supracolic reconstruction. Supra- and infracolic reconstruction have not yet been
      compared. PATIENTS: 138 patients underwent pylorus-preserving
      pancreatoduodenectomy with retrocolic reconstruction at our department between
      2011 and 2017. Of these, 105 were reconstructed with supracolic
      duodenoenterostomy and 33 with infracolic duodenoenterostomy. Patients were
      analysed with respect to demographic factors, diagnosis, pre-existing conditions,
      intraoperative characteristics, hospital stay and morbidity and mortality with
      special emphasis on DGE. All complications were classified according to the
      definitions of the International Study Group on Pancreatic Surgery. RESULTS: The
      two groups were comparable with respect to diagnosis, medical history,
      intraoperative characteristics, morbidity and mortality. DGE was equally
      distributed between supra- and infracolic reconstruction (DGE stage A/B/C25/14/10
      vs. 12/5/2, p = 0.274). With DGE, intensive care unit stay (p = 0.007) and
      hospital stay (p = 0.001) are significantly delayed. Risk factor analysis showed
      that pre-existing diabetes (p = 0.047) and major complications (Clavien stage III
      - V, p = 0.048) are risk factors for DGE, while the use of somatostain-analogues
      seems to have a protective effect (p = 0.021). CONCLUSION: Supra- or infracolic
      reconstruction does not influence the frequency of DGE following
      pancreatoduodenectomy. When DGE occurs, hospital stay is delayed. Somatostatin
      analogues may act prophylactically on DGE.

PMID- 30206910
TI  - [The Foot in Language, Symbols, and Myths].
AB  - In the history of evolution, the human foot is the youngest part of our skeleton
      and allows plane bipedal walking due to development of a longitudinal and
      transverse arch of the foot, with a stable, parallel first ray, but sacrificing
      the ability to grasp. Due to the loss of grasping, the hominoid mothers had to
      lay down their babies while working. To prevent babies from crying in dangerous
      surroundings with wild animals, mothers had to calm them with sounds and singing
      that likely led to language. A third somehow synchronous step was growth of the
      telencephalon and the development of specialised hands that could produce tools
      for fishing and hunting. As these elementary changes allowed upright walking and
      the discovery of new worlds, the foot is really deeply anchored in our speech and
      has become a symbol for life itself, for the human being as a "pars pro toto",
      for freedom, power and subjection. According to many myths, metaphors and symbols
      for the foot also represent life-spending fertility, eroticism, and sexuality.
      But nevertheless the foot is also a symbol of respect, reverence, and
      subservience, feet washing and anointing is an act of humility and love. At least
      we know nowadays that the foot is a subconscious ambassador of our emotions in
      non-verbal communication. With the help of our feet, we can hunt each other or
      approach each other, not only symbolically, but also in fact.

PMID- 30206911
TI  - Arthroscopic Anterior Cruciate Ligament Reconstruction: A Meta-Analysis Comparing
      Semitendinosus Alone and Semitendinosus with Gracilis Tendon Autografts.
AB  - The objective of this study was to provide a comprehensive systematic review and
      meta-analysis to compare patient-reported outcomes and functional knee parameters
      of anterior cruciate ligament (ACL) reconstruction surgery with semitendinosus
      (ST) and ST-gracilis (G) grafts. This study was conducted according to Preferred
      Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta
      Analysis of Observational Studies in Epidemiology (MOOSE) guidelines. All studies
      in PubMed and Embase that reported functional knee parameters and patient
      reported outcomes after ACL reconstruction with ST and ST-G grafts independently
      were included in the review. Selected end points for random effects, pairwise
      meta-analysis included side-to-side deficit (%) in isokinetic peak torque, peak
      torque ratio (%), side-to-side difference (mm) in anterior laxity, and patient
      reported outcome scores at minimum 2-year follow-up. A total of 15 primary
      references comprising 1,109 participants were identified. The ST group had
      decreased side-to-side deficit in isokinetic peak torque when compared with the
      ST-G group for flexion at 60 degrees/s (p = 0.02) and 180 degrees/s (p = 0.01) at
      2-year follow-up. There were no significant differences in side-to-side
      difference in anterior laxity (p = 0.81), hamstring/quadriceps peak torque ratios
      at 60 degrees/s (p = 0.83) and 180 degrees/s (p = 0.36), and patient-reported
      outcomes in the International Knee Documentation Committee score (p = 0.06) and
      Lysholm score (p = 0.67). The addition of the gracilis tendon to the hamstring
      autograft in ACL reconstruction results in increased side-to-side deficits in
      isokinetic peak flexion torque. However, patient-reported outcome scores and knee
      laxity measurements are comparable with those of ST grafts.

PMID- 30206912
TI  - Treatments of Choice for Isolated, Full-Thickness Tears of the Posterior Cruciate
      Ligament: A Nationwide Survey of Orthopaedic Surgeons.
AB  - The ideal treatment for isolated, full-thickness tears of the posterior cruciate
      ligament (PCL) is uncertain. The purpose of this study was to determine how the
      majority of orthopaedic surgeons treat isolated, full-thickness tears of the PCL.
      In July 2017, a 17-question multiple-choice survey regarding the treatment of
      isolated, full-thickness tears of the PCL was emailed to 3,500 orthopaedic sports
      medicine surgeons with membership in the American Orthopaedic Society for Sports
      Medicine. Responders answered multiple-choice questions related to indications,
      technique, graft choice, bracing, and weight-bearing status following
      reconstruction. Answer choices were then analyzed against surgeon-specific
      variables. The survey was completed by 663 orthopaedic surgeons. Of the
      responders, 93% were fellowship trained in sports medicine with an average
      practice duration of 13 years. The total number of PCLs reconstructed per surgeon
      was low, 11.6. On average, surgeons estimate they reconstruct the PCL in only 22%
      of patients with full-thickness tears. The two most common surgical indications
      were functional limitations and failure of physical therapy. The reconstruction
      of choice involves a transtibial approach (63%) with a single bundle (87%)
      allograft (83%) of the Achilles tendon (51%). The postoperative brace is
      typically locked in extension (66%), and weight-bearing is delayed for 3.8 weeks.
      Of the surgeons with the fewest years of experience, 39% use all-inside, 89% use
      allograft, and 24% use dynamic bracing. Compared with surgeons with the most
      years of experience, only 16% use all-inside (p < 0.01), 57% use allograft (p <
      0.01), and 11% use dynamic bracing (p = 0.01). Isolated, full-thickness tears of
      the PCL are rare injuries that are infrequently reconstructed. The most common
      indications for reconstruction are functional limitations and failure of
      conservative management. Most surgeons' treatment of choice for reconstruction
      involves a transtibial approach with a single bundle Achilles allograft and a
      postoperative brace locked in extension. On average, weight-bearing is prolonged
      for 3.8 weeks. The all-inside technique, allograft, and dynamic bracing are
      becoming more popular.

PMID- 30206913
TI  - Peroneus Longus Tendon Autograft is a Safe and Effective Alternative for Anterior
      Cruciate Ligament Reconstruction.
AB  - The ipsilateral peroneus longus tendon (PLT) was utilized as an autograft for
      anterior cruciate ligament (ACL) reconstruction of patients with acute ACL
      rupture and grade III medial collateral ligament (MCL) injury. We investigated
      the efficacy and safety of this alternative autograft compared with autologous
      hamstring tendon (HT). Biomechanical testing of the graft options was performed
      and compared with the native ACL. Thirty-eight patients with acute ACL ruptures
      and grade III MCL injuries were treated with ACL reconstruction with a doubled
      autologous PLT or quadrupled autologous HT. Knee stability and function was
      evaluated clinically with the Lachman test and KT-2000 arthometer as well as
      subjectively with functional scores. Effects on the donor ankle were evaluated by
      biomechanical testing. The ultimate tensile strengths of doubled PLT and
      quadrupled HT were significantly higher than that of the native ACL and the
      ultimate tensile strength of doubled PLT was comparable with that of quadrupled
      HT. There were no significant differences in clinical or functional scores
      between the two groups. There were no significant differences in pre- and
      postoperative biomechanical testing of the donor ankle. PLT is a suitable
      alternative autograft for an ACL reconstruction in patients with a concomitant
      grade III MCL injury without a significant biomechanical disadvantage to the
      ankle donor site.

PMID- 30206915
TI  - The Less You Are, the More You Are Helped: Effect of Kinesio Tape on Temporal
      Coordination.
AB  - We investigated whether a relationship exists between the inherent timing skill
      of subject and the magnitude of effect of KT on timing performance by expanding
      the examination of the dataset described in our previous work. Healthy subjects,
      tested with and without KT (NKT), performed sets of repetitive wrist's flexion
      extensions (IWFEs) with the dominant limb (DL) and the non-dominant limb (NDL) in
      a synchronization-continuation task at two inter-onset intervals (IOIs): 550-ms
      and 800-ms. Standard deviation (SD) of IWFEs was used to measure the unevenness
      of performance. Different patterns of response to KT were observed based on the
      participant's inherent precision. In the NDL the effect of KT was found
      significantly higher in the subgroups of individuals having SDNKT of IWFEs>38 ms
      (p=0.0024) in the 800-ms IOI or SDNKT of IWFEs>19 ms (p=0.0004) in the 550-ms
      IOI. In the DL the effect of KT was not influenced by the inherent timing skill.
      We propose KT to be tested for restoring motor control on subjects experiencing
      sensorimotor disorders associated with intense repetitive training. Also, our
      findings suggest that care should be taken when using groups of healthy subjects
      to test the effect of KT.

PMID- 30206914
TI  - [Updated S3-Guideline Colitis ulcerosa. German Society for Digestive and
      Metabolic Diseases (DGVS) - AWMF Registry 021/009].
AB  - This guideline provides evidence-based key recommendations for diagnosis and
      treatment of ulcerative colitis and upgrades the 2011 version. The guideline was
      developed by an interdisciplinary team of gastroenterologists, surgeons,
      pathologists, nutrition experts, and patient support groups under the auspice of
      the German Society for Gastroenterology and Metabolic Diseases. The guideline
      used structural S3 consensus-based methodology and includes statements on
      clinical practice, prevention, infectiological problems, surgery and nutrition.

PMID- 30206916
TI  - Upper Extremity Pain and Pitching Mechanics in National Collegiate Athletic
      Association (NCAA) Division I Softball.
AB  - The purpose of this study was to evaluate pitching mechanics between female
      softball pitchers with upper extremity pain and those without upper extremity
      pain. Specifically, the trunk, shoulder and elbow kinematics and shoulder
      kinetics during the change-up softball pitch were examined. Fifty-five collegiate
      softball pitchers participated, divided into those with upper extremity pain
      (20.0+/-1.3 yrs.; 174.4+/-6.9 cm; 82.9+/-12.4 kg; 11.1+/-2.6 yrs. of experience;
      n=23) and those who were pain-free (19.9+/-1.4 yrs.; 173.8+/-6.9 cm; 81.4+/-12.5
      kg; 10.0+/-2.5 yrs. of experience; n=32). Pitching mechanics were obtained via
      the trakSTARTM electromagnetic tracking system (Ascension Technologies, Inc.,
      Burlington, VT, USA). Mann-Whitney U tests revealed significant differences in
      shoulder horizontal abduction at foot contact (p=0.014, U=153, Z=2.450) and trunk
      lateral flexion at ball release (p=0.012, U=150, Z=-2.515); and between shoulder
      distraction force at ball release (p=0.034, U=168, Z=-2.124). The pain group
      illustrated greater shoulder horizontal abduction at foot contact, less trunk
      lateral flexion towards the throwing side at ball release, and greater shoulder
      distraction at ball release than the pain-free group. The differences in trunk
      and shoulder kinematics, and shoulder kinetics between groups allows for insight
      into further studies examining injury pervasiveness in softball pitching.

PMID- 30206917
TI  - Sex- and Mode-specific Responses to Eccentric Muscle Fatigue.
AB  - The primary purpose of the present investigation was to examine sex-related
      differences as a result of fatiguing eccentric muscle actions on torque, muscle
      blood flow, electromyography, and mechanomyography. Eighteen men and 18 women
      performed peak torque trials prior to (pretest), immediately after (posttest),
      and 5-min after (recovery) completing 50 submaximal (60% of eccentric peak
      torque), eccentric, isokinetic (180 degrees .s -1) muscle actions of the elbow
      flexors. Electromyographic and mechanomyographic responses were simultaneously
      recorded from the biceps brachii muscle, and muscle blood flow was measured at
      pretest, posttest and recovery. There were sex- and mode-specific responses for
      torque, but there were no sex-specific muscle blood flow or neuromuscular
      responses. From pretest to posttest, torque decreased (80.0-88.2% of pretest) for
      both the men and women. At recovery concentric peak torque recovered to a greater
      extent in women (95.0% of pretest) than men (88.0% of pretest), while eccentric
      peak torque recovered to a greater extent in men (88.9% of pretest) than women
      (86.9% of pretest). The sex-specific torque responses were not associated with
      different motor control strategies or differences in the occlusion of muscle
      blood flow between the men and women. For both men and women, eccentric fatiguing
      exercise is manifested similarly during isometric muscle actions, but not during
      eccentric and concentric muscle actions.

PMID- 30206918
TI  - Wheelchair Skills Training for Functional Activity in Adults with Cervical Spinal
      Cord Injury.
AB  - Wheelchair skills training can improve independent wheeled mobility for daily
      living activities as well as functional and social participation of adults with
      cervical spinal cord injury (C-SCI). The objective of this study was to examine
      the effectiveness of wheelchair skills training in improving both wheelchair
      skills and upper arm skilled performance in adults with C-SCI. In a randomized
      controlled study, 24 adults with tetraplegia were randomized and allocated to
      training group (n=13) or control group (n=11). The training group attended
      wheelchair skills training sessions, whereas the control group attended
      conventional exercise sessions. All interventions lasted 8 weeks, with a
      frequency of 3 days per week. All individuals were tested with the Wheelchair
      Skills Test (WST) and the Van Lieshout Test (VLT). The test was repeated at pre-
      and post-training (after 4 weeks and 8 weeks). For WST, univariate analysis
      demonstrated significant main effects in between-group, within-group, and group
      by-time interaction (p<0.05). VLT showed no significant effect in between-group
      comparison (p>0.05), whereas within-group comparison of test times and group-by
      time interaction showed significant main effects (p<0.05). Thus, wheelchair
      skills training is more beneficial for adults with C-SCI than conventional
      exercise.

PMID- 30206919
TI  - Evaluating the Psychometric Properties of the Persian Self-Management Scale for
      Kidney Transplant Recipients.
AB  - PURPOSE: There was no appropriate instrument for assessing the self-management of
      Iranian kidney transplant recipients. This study was done to translate the Self
      Management Scale for Kidney Transplant Recipients into Persian and evaluate its
      psychometric properties. MATERIAL AND METHODS: This cross-sectional
      methodological study was done from October 2016 to March 2017. The psychometric
      properties of the scale were evaluated in the following four steps: forward
      backward translation, face and content validity assessments, construct validity
      assessment via exploratory factor analysis, and reliability assessment via
      internal consistency and test-retest techniques. RESULTS: The means of item
      impact score, content validity ratio, and simplicity, clarity, and relevance
      content validity indices were 3.94, 0.73, 0.96, 0.93, and 0.98, respectively.
      Exploratory factor analysis revealed a four-factor structure for the scale which
      explained 70.75% of the total self-management variance. The four factors of the
      scale were "self-monitoring", "self-care behaviors", "early detecting and coping
      with abnormalities", and "drug management". The Cronbach's alpha and the test
      retest intraclass correlation coefficient of the scale were 0.73 and 0.90,
      respectively. CONCLUSION: The Persian Self-Management Scale for Kidney Transplant
      Recipients has acceptable validity and reliability. It can be used in educational
      and clinical environments and also in research studies for measuring kidney
      transplant recipients' self-management.

PMID- 30206920
TI  - Management of Large Proximal Ureteral Calculi: A Three-year Multicenter
      Experience of Simultaneous Supine Percutaneous Nephrolithotomy and Retrograde
      Ureterolithotripsy.
AB  - PURPOSE: To share our multicenter experience using a safe and effective method
      for treating large proximal ureteral calculus by simultaneous supine percutaneous
      nephrolithotomy (sPCNL) and retrograde ureterolithotripsy (URSL) in the Galdakao
      modified supine Valdivia position. MATERIALS AND METHODS: Between December 2014
      and August 2017, all patients with large proximal ureteral stones (> 15 mm) who
      underwent simultaneous sPCNL and retrograde URSL at three medical centers were
      retrospectively reported. The ureter stone was pushed back (retrograde) with the
      ureteroscope and was retrieved using forceps with a nephroscope through an
      Amplatz sheath. Surgical methods and outcomes were described to improve our
      experience and management of large proximal ureteral calculi. RESULTS: A total of
      31 patients underwent simultaneous sPCNL and retrograde URSL. The mean patient
      age, stone size, operating time, and postoperative hospital stay were 57 years
      (range, 32-74 years), 20.1 mm (range, 15.0-37.9 mm), 81 minutes (range, 30-150),
      and 3.2 days (range, 2-7 days), respectively. There were 10 modified Clavien
      grade I and five grade II complications. No blood transfusions were necessary in
      this series. All patients were treated with double-J stents without a nephrostomy
      tube. Only one patient did not achieve stone-free status because of the strict
      stone impaction into the ureteral wall. This patient received auxiliary URSL
      after two months. Thereafter, the overall stone-clearance rate at three months
      was 100%. CONCLUSION: Our preliminary data showed that this modified method is
      safe and effective for treating large proximal ureteral stones.

PMID- 30206921
TI  - Impact and Predictive Value of Prostate Weight on the Outcomes of Nerve Sparing
      Laparoscopic Radical Prostatectomy in Patients with Low Risk Prostate Cancer.
AB  - PURPOSE: To investigate the impact of prostate weight on outcomes of nerve
      sparing laparoscopic radical prostatectomy (LRP) and assess its predictive value
      on postoperative continence and potency recovery. MATERIALS AND METHODS: We
      conducted a retrospective study on the clinical data of 165 patients with low
      risk prostate cancer (PCa) who underwent nerve sparing LRP. All the patients
      included had normal preoperative urinary and sexual function. The association of
      prostate weight with perioperative data was assessed using Spearman correlation
      coefficient. Univariate and multivariate Cox regression analyses were employed to
      identify prognostic predictors for continence and potency recovery. RESULTS:
      Increased prostate weight was significantly associated with older age, higher
      prostate-specific antigen (PSA), lower biopsy and pathological T stage and
      Gleason score, longer operative time, and higher estimated blood loss (P < .05).
      The continence rates at the 3rd, 6th, and 12th month after surgery were 63.6%
      (105/165), 87.9% (145/165), and 95.8% (158/165); and the potency rates were 44.8%
      (74/165), 62.4% (103/165) and 77.6% (128/165), respectively. Furthermore,
      multivariate Cox analysis showed that patient age (HR = 0.52, 95% CI: 0.35-0.76)
      and prostate weight (HR = 0.54, 95% CI: 0.34-0.86) were independent predictors
      for continence recovery, while only patient age (HR = 0.66, 95% CI: 0.45-0.96)
      could independently predict potency recovery. CONCLUSION: Larger prostate size
      was correlated with older age, higher PSA, lower tumor stage and grade, longer
      operative time, and more intraoperative blood loss in low risk PCa patients.
      Increased prostate weight may independently predict poor continence recovery
      after nerve sparing LRP.

PMID- 30206922
TI  - The Effect of Heroin Addiction on Human Sperm Parameters, Histone-To-Protamine
      Transition, and Serum Sexual Hormone Levels.
AB  - PURPOSE: To investigate the effects of heroin on sperm parameters, histone-to
      protamine transition ratios in mature sperm, and serum reproductive hormone
      levels in active heroin users. MATERIALS AND METHODS: Semen and blood samples
      were collected from 25 men who used only heroin for at least 12 months and the
      same number healthy men who did not use any drugs and did not suffer from
      infertility problems. Computer-based analysis, Aniline blue staining, and
      Hormones assessment were performed to provide valuable new information on the
      relationship between addiction and semen profile and serum reproductive hormone
      levels. RESULTS: Our finding showed that semen PH (7.8 vs. 7.75), sperm motility
      (42.93 +/- 3.89% vs. 68.9 +/- 2.68%), and viability (73.27 +/- 3.85% vs. 86.48 +/
      1.05%), and sperm histone replacement abnormalities (32.33 +/- 10.89% vs. 5.56
      +/- 0.85%) were significant differences in addicted group vs. non-exposed ones (P
      ? .05). In addition, serum sex hormone levels were not significantly differed
      between groups. There was a correlation between the amount of daily heroin
      consumption and LH level. We also observed that duration of drug dependence is
      correlated with sperm abnormalities. CONCLUSIONS: We concluded that heroin
      consumption affect sperm maturities such as histone-to-protamine ratio and impair
      semen profile in general and particularly sperm morphology and motility. Heroin
      may be considered as one of the idiopathic male infertility reason.

PMID- 30206923
TI  - Evaluation and Comparison of Metabolic Disorders between Patients with Unilateral
      and Bilateral Staghorn Renal Stones.
AB  - PURPOSE: Metabolic disorders are common in patients with staghorn renal stones.
      Aim of this study was to evaluate and compare the metabolic disorders in patients
      with unilateral and bilateral staghorn stones. MATERIALS AND METHODS: In this
      cross sectional study, 78 patients who underwent percutaneous nephrolithotomy
      (PCNL) for staghorn renal stones were included. The urine volumes, the levels of
      calcium, oxalate, uric acid, phosphate, sodium, citrate, creatinine, and cystine
      from 24 hour urine collection as well as the serum levels of calcium, phosphorus,
      magnesium, creatinine, blood urea nitrogen (BUN), parathyroid hormone (PTH) and
      uric acid were recorded and compared among the two groups with unilateral and
      bilateral renal stones. RESULTS: 56 patients (71.8%) had unilateral and 22
      (28.2%) had bilateral renal stones. At least one abnormal metabolic factor was
      found in 32 (57.1%) and 15 (68.2%) patients with unilateral and bilateral renal
      stones, respectively (P = .044). Cystine urine levels and serum levels of BUN
      were higher in cases with bilateral compared to unilateral renal stones (36.4%
      vs. 12.5%, P = .025 and 27.3% vs. 1.8%, P = .002, respectively). CONCLUSION:
      Metabolic factors are strongly correlated with the formation of staghorn renal
      stones specially bilateral ones. In our study among different metabolic factors,
      cystine urine levels and serum levels of BUN were significantly higher in
      patients with bilateral renal stones. Proper metabolic assessments are
      recommended in patients with staghorn urolithiasis.

PMID- 30206924
TI  - Primary Prostate Lymphoma Managed with Combined Modality Treatment: A Case
      Report.
AB  - Prostate cancer is one of the most common malignancies in men; the main reported
      pathology is adenocarcinoma while there are few published cases of prostate
      lymphoma. There isn't enough data regarding the natural history and best
      management of prostate lymphoma. In this paper, we have described a case of
      prostate lymphoma that managed with combined modality treatment and have been
      survived for three years.

PMID- 30206925
TI  - Comparison of Two Different Anesthesia Methods In Patients Undergoing
      Percutaneous Nephrolithotomy.
AB  - PURPOSE:   The study aims to compare the effectiveness, safety and costs of two
      different anesthesia methods in PCNL (percutaneous nephrolithotomy) operations.
      MATERIAL-METHOD: In our study, data was retrospectively examined of 1657 patients
      who underwent PCNL due to renal calculi between 2009 and 2017. Patients were
      separated into two groups according to the type of anesthesia; as those
      implemented PCNL under general anesthesia (GA) (n=572) and those under spinal
      anesthesia(SA) (n=1085). Standard PCNL technique was used in both groups. Gender,
      age, operation duration, period of hospitalization, stone-free ratio, post
      operative narcotic analgesic need and complications were compared between these
      two groups. RESULTS: A total of 1657 patients consisting of 1064 (64.2%) male
      patients and 593 (35.8%) female patients were included in the study. The average
      age of the all patients was 33.2+/-12.4 (range 16-74) years. The two groups were
      similar in terms of mean age, gender, stone size, stone location and body mass
      index. Mean operation time was significantly shorter in the SA group than in the
      GA group (81.8+/-33.9 minute vs. 118.2+/--42.9 minute respectively, p<.001). Mean
      period of hospitalization was remarkable shorter in the SA group than in the GA
      group (30.0+/-9.9 hours vs. 38.4+/-11.2 hours respectively, p<.001). Post
      operative narcotic analgesic need rate was significantly higher  in the GA group
      than in the SA group (33.4% vs. 10.9%, respectively, P<.001). Anesthesia cost was
      found significantly lower in the SA group than in the GA group (USD 21.3+/-2.8
      vs. USD 83.6+/-9.5, respectively, p<.001). Significant difference was not
      observed between both groups in terms of stone-free ratio, amount of bleeding,
      fluoroscopy time, pre-operative and post-operative complications. CONCLUSION:
      Compared to those performed with GA, PCNL performed with SA is a safe, effective
      and low-cost method.

PMID- 30206926
TI  - Effect of Unilateral Iatrogenic Torsion onContralateral Testis inRat, Prepubertal
      and Postpubertal.
AB  - PURPOSE: The present study was conducted to investigate the influence of
      hemicastration and age at hemicastration on the subsequent contralateral testis.
      MATERIALS AND METHODS: 64 Wistar-derived male rats divided randomly in 4 groups.
      Group 1 named immature intervention, group 2 immature control, group 3 mature
      intervention and group 4mature control. In group 1, rats hemicastrated at 30 days
      of age (prepubertal). In group 2 sham surgery (midscrotal incision) was done at
      same age. In group 3 rats hemicastrated at 70 days of age (postpubertal) and in
      group 4 sham surgery was done at same age. 20 days after first surgery,
      contralateral orchiectomy was donein intervention groups and random orchiectomy
      (left or right) was donein control groups. Blood sampling for evaluation of serum
      testosterone was performed just before second surgery. RESULTS: Testis weight
      (1692 +/- 26.7 in Group 1 vs 1375 +/- 39.7 in Group 2; P< 0.001 and 1760 +/- 26.6
      in Group 3 vs 1425 +/- 44.9 in Group 4; P< 0.001) and the mean testicular weight
      (mg) per 100 g of body weight (735.8 +/- 82.3 in Group 1 vs 634.8 +/- 84.8 in
      Group 2; P = 0.005 and 652.4 +/- 61.4 in Group 3 vs 572.6 +/- 97.7 in Group 4; P
      = 0.03) was greater in hemicastrated rats. These parameters was greater in
      prepubertal group than postpubertal hemicastrated rats. There was no appreciable
      difference in serum testosterone levels in 4 groups (P = 0.77). CONCLUSION: Our
      research demonstrated that hemicastration resulted in compensatory hypertrophy of
      the remaining testis and it decreased as the animals aged. Hemicastration does
      not lead to reduction in serum testosterone levels and remaining testis can
      retrieve a normal serum testosterone level.

PMID- 30206927
TI  - A Case Report of Synchronous Prostate Cancer and Rectal Gastrointestinal Stromal
      Tumor and its Management.
AB  - A 72-year-old Japanese man presented to the hospital with complaints of gross
      hematuria. Contrast enhanced computed tomography revealed a broad-based,
      approximately 3-cm bladder tumor near the right ureteral orifice and a 5-cm mass
      located between the prostate and rectum. The patient underwent transurethral
      resection of the bladder tumor and a transrectal biopsy of the lesion.
      Histological examination of the specimens suggested that the patient had a muscle
      invasive adenocarcinoma from TURBT and a rectal gastrointestinal stromal tumor in
      TRUS biopsy. Patient underwent total pelvic exenteration and ileal and colonic
      stomas to divert urine and faeces. Final pathology report of the resected
      specimen revealed a rectal gastrointestinal stromal tumor and prostatic
      adenocarcinoma, which had invaded the urinary bladder and seminal vesicles.
      Synchronous gastrointestinal stromal tumor in rectum and prostate cancer treated
      with total pelvic exenteration not before reported in literature. So we report
      this case, along with review of literature.

PMID- 30206928
TI  - Contribution of self-compassion to positive mental health among Korean university
      students.
AB  - Although evidence suggests self-compassion can serve as an important predictor of
      positive mental health, few studies have examined the contribution of self
      compassion to mental health. This study examined the relations between six
      components of self-compassion and three dimensions of positive mental health
      (Psychological, Emotional and Social Well-being) in young Korean adults. A sample
      of 689 Korean college students were administered the Self-Compassion Scale (SCS)
      and the Mental Health Continuum Short Form (MHC-SF) to evaluate self-compassion
      and positive mental health. A multiple indicators multiple causes (MIMIC)
      analysis revealed that Self-Kindness significantly predicted all dimensions of
      positive mental health. Additionally, Over-Identification significantly
      contributed to Emotional Well-being, Common Humanity to Social Well-being and
      Isolation to Psychological Well-being. These results suggest Self-Kindness is a
      key predictor of positive mental health and that specific components of self
      compassion are strongly related to specific dimensions of mental health in
      Koreans.

PMID- 30206929
TI  - MicroRNA-520a-3p suppresses epithelial-mesenchymal transition, invasion, and
      migration of papillary thyroid carcinoma cells via the JAK1-mediated JAK/STAT
      signaling pathway.
AB  - Papillary thyroid cancer (PTC) is a kind of thyroid cancer and frequently
      presents with epithelial-mesenchymal transition (EMT). MicroRNAs (miRNAs) were
      previously reported to be associated with PTC. Thus, this study aims to define
      the role of microRNA-520a-3p (miR-520a-3p) in PTC through the JAK/STAT signaling
      pathway by targeting JAK1. The PTC and normal thyroid tissues of 137 PTC patients
      were collected. First of all, the expression pattern of miR-520a-3p, JAK1, JAK2,
      STAT3, E-cadherin, and vimentin in PTC was identified. The relationship between
      miR-520a-3p and JAK1 was predicted and analyzed. And a series of miR-520a-3p
      mimic or inhibitor, or siRNA JAK1 introduced into PTC cells were applied to
      examine the effect of miR-520a-3p on PTC cell viability, migration, invasion,
      cell cycle, apoptosis, and EMT. Meanwhile, the regulatory effect of miR-520a-3p
      and JAK1 on the JAK/STAT signaling pathway was also determined. The expression of
      JAK1, JAK2, STAT3, and vimentin increased yet miR-520a-3p and E-cadherin
      decreased in PTC tissue. JAK1 was negatively regulated by miR-520a-3p.
      Functionally, EMT induction was prevented by miR-520a-3p upregulation through
      downregulating JAK1. When upregulating miR-520a-3p or silencing JAK1 in PTC
      cells, PTC cell viability, migration, and invasion were inhibited yet cell
      apoptosis promoted with cells arrested at G1 phase, indicating that miR-520a-3p
      prevented PTC progression by downregulating JAK1. Moreover, miR-520a-3p elevation
      or JAK1 inhibition inactivated the JAK/STAT signaling pathway. Collectively, miR
      520a-3p prevents cancer progression through inactivating the JAK/STAT signaling
      pathway by downregulating JAK1 in PTC.

PMID- 30206930
TI  - Cucurbitacin B suppresses proliferation of pancreatic cancer cells by ceRNA:
      Effect of miR-146b-5p and lncRNA-AFAP1-AS1.
AB  - Cucurbitacin B (CuB) is a natural tetracyclic triterpene product that displays
      antitumor activity against a wide variety of cancers. In this study, we explored
      the antipancreatic cancer activity of CuB via the inhibition of expression of the
      cancer-related long noncoding RNA, actin filament-associated protein 1-antisense
      RNA 1 (AFAP1-AS1). CuB arrested pancreatic cancer (PC) cells in the G2/M cell
      cycle phase by suppressing the expression of AFAP1-AS1. Insights into the
      mechanisms of competing endogenous RNAs (ceRNAs) gained from bioinformatics
      analysis and luciferase activity assays showed that the epidermal growth factor
      receptor (EGFR) and AFAP1-AS1 directly compete for miR-146b-5p binding. CuB
      induced high miR-146b-5p expression and inhibited the expression of AFAP1-AS1. In
      summary, reducing the expression of endogenous AFAP1-AS1 effectively increased
      the available concentration of miR-146b-5p in PC, whereas miR-146b-5p
      overexpression prevented the expression of endogenous AFAP1-AS1. In particular,
      we hypothesized that AFAP1-AS1 might act as a ceRNA, effectively becoming a
      sponge for miR-146b-5p, thereby activating the expression of the EGFR. Thus, CuB
      suppresses the proliferation, in vitro and in vivo, of PC cells through the ceRNA
      effect of AFAP1-AS1 on miR-146b-5p.

PMID- 30206931
TI  - Cell communication by tunneling nanotubes: Implications in disease and
      therapeutic applications.
AB  - Intercellular communication is essential for the development and maintenance of
      multicellular organisms. Tunneling nanotubes (TNTs) are a recently recognized
      means of long and short distance communication between a wide variety of cell
      types. TNTs are transient filamentous membrane protrusions that connect cytoplasm
      of neighboring or distant cells. Cytoskeleton fiber-mediated transport of various
      cargoes occurs through these tubules. These cargoes range from small ions to
      whole organelles. TNTs have been shown to contribute not only to embryonic
      development and maintenance of homeostasis, but also to the spread of infectious
      particles and resistance to therapies. These functions in the development and
      progression of cancer and infectious disease have sparked increasing scrutiny of
      TNTs, as their contribution to disease progression lends them a promising
      therapeutic target. Herein, we summarize the current knowledge of TNT structure
      and formation as well as the role of TNTs in pathology, focusing on viral, prion,
      and malignant disease. We then discuss the therapeutic possibilities of TNTs in
      light of their varied functions. Despite recent progress in the growing field of
      TNT research, more studies are needed to precisely understand the role of TNTs in
      pathological conditions and to develop novel therapeutic strategies.

PMID- 30206932
TI  - Cytoplasmic p27Kip1 promotes tumorigenesis via suppression of RhoB activity.
AB  - The cell cycle inhibitor p27Kip1 is a tumor suppressor via the inhibition of CDK
      complexes in the nucleus. However, p27 also plays other functions in the cell and
      may acquire oncogenic roles when located in the cytoplasm. Activation of
      oncogenic pathways such as Ras or PI3K/AKT causes the relocalization of p27 in
      the cytoplasm where it can promote tumorigenesis by unclear mechanisms. Here, we
      investigated how cytoplasmic p27 participates in the development of non-small
      cell lung carcinomas. We provide molecular and genetic evidence that the
      oncogenic role of p27 is mediated at least in part by binding to and inhibiting
      the GTPase RhoB, which normally acts as a tumor suppressor in the lung.
      Genetically modified mice revealed that RhoB expression is preferentially lost in
      tumors in which p27 is absent and maintained in tumors expressing wild-type p27
      or p27CK- , a mutant that cannot inhibit CDKs. Moreover, while the absence of
      RhoB promoted tumorigenesis in p27-/- animals, it had no effect in p27CK- knock
      in mice, suggesting that cytoplasmic p27 may act as an oncogene at least in part
      by inhibiting the activity of RhoB. Finally, in a cohort of lung cancer patients,
      we identified a subset of tumors harboring cytoplasmic p27 in which RhoB
      expression is maintained and these characteristics were strongly associated with
      decreased patient survival. Thus, monitoring p27 localization and RhoB levels in
      non-small cell lung carcinoma patients appears to be a powerful prognostic marker
      for these tumors.

PMID- 30206933
TI  - Tumor suppressive function of E2F-1 on PTEN-induced serrated colorectal
      carcinogenesis.
AB  - Many human cancers present Phosphatase and tensin homolog (PTEN) deficiency and
      between 20 and 30% of colorectal tumors show PTEN loss. The transcription factor,
      E2 promoter binding factor 1 (E2F-1), exhibits tumor promoter or suppressive
      functions depending on cellular type and tissue context, but its role in the
      progression and development of colorectal carcinogenesis was largely unknown.
      Here, using a tamoxifen-inducible PTEN knockout mouse model, we have demonstrated
      that loss of PTEN leads to the development of colorectal tumorigenesis through
      the serrated pathway. Next, we studied PTEN loss-driven colorectal lesions in the
      context of E2F-1 deficiency in vivo. Our results revealed that monoallelic and
      biallelic absence of E2F-1 led to an increased incidence and progression of
      serrated tumorigenesis induced by PTEN loss. Finally, we investigated the
      mechanisms by which double PTEN/E2F-1 deficiency leads to enhanced tumorigenesis.
      We found that colorectal tumors from PTEN/E2F-1 double knockout mice and the
      human colorectal carcinoma cell line HT29 with shRNA-mediated downregulation of
      PTEN and E2F-1 exhibit hyperactivation of the RAS-MAPK pathway, accumulation of
      DNA damage and resistance to apoptosis. To date, this is the first preclinical
      study evaluating the effect of genetic deletion of E2F-1 in colorectal
      malignancies driven by PTEN deficiency. Copyright (c) 2018 Pathological Society
      of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

PMID- 30206934
TI  - Cyclic tensile force stimulates BMP9 synthesis and in vitro mineralization by
      human periodontal ligament cells.
AB  - Periodontal ligament (PDL) cells are mechanosensitive and have the potential to
      differentiate into osteoblast-like cells under the influence of cyclic tensile
      force (CTF). CTF modulates the expression of regulatory proteins including bone
      morphogenetic proteins (BMPs), which are essential for the homeostasis of the
      periodontium. Among the BMPs, BMP9 is one of the most potent osteogenic BMPs. It
      is yet unknown whether CTF affects the expression of BMP9 and mineralization.
      Here, we demonstrated that continuously applied CTF for only the first 6 hr
      stimulated the synthesis of BMP9 and induced mineral deposition within 14 days by
      human PDL cells. Stimulation of BMP9 expression depended on ATP and P2Y 1
      receptors. Apyrase, an ecto-ATPase, inhibited CTF-mediated ATP-induced BMP9
      expression. The addition of ATP increased the expression of BMP9. Loss of
      function experiments using suramin (a broad-spectrum P2Y antagonist), MRS2179 (a
      specific P2Y 1 receptor antagonist), MRS 2365 (a specific P2Y 1 agonist), U-73122
      (a phospholipase C [PLC] inhibitor), and thapsigargin (enhancer of intracytosolic
      calcium) revealed the participation of P2Y 1 in regulating the expression of
      BMP9. This was mediated by an increased level of intracellular Ca 2+ through the
      PLC pathway. A neutralizing anti-BMP9 antibody decreased mineral deposition,
      which was stimulated by CTF for almost 45% indicating a role of BMP9 in an in
      vitro mineralization. Collectively, our findings suggest an essential modulatory
      role of CTF in the homeostasis and regeneration of the periodontium.

PMID- 30206935
TI  - The Effects of Provider Choice Policies on Workers' Compensation Costs.
AB  - OBJECTIVE: To examine the effects of provider choice policies on workers'
      compensation medical and indemnity costs. DATA SOURCES/STUDY SETTING: Pooled
      cross-sectional analysis of administrative claims records for workers with work
      related injuries primarily in 2007-2010 across 25 states (n = 4,489,729). STUDY
      DESIGN: We used linear and quantile regression analyses to evaluate differences
      in claim costs (medical and indemnity) based on whether policies give employers
      or injured workers control over the choice of provider. PRINCIPAL FINDINGS: We
      find no difference in average medical costs by provider choice policies, although
      a distributional analysis indicates higher developed medical costs for the
      costliest back injury cases in states where workers control provider choice. The
      evidence for indemnity costs is similar, although the point estimates also
      indicate (statistically insignificantly) higher average costs when policies give
      workers more control of the choice of provider. CONCLUSIONS: Our nuanced evidence
      suggests that policymakers seeking to reduce workers' compensation costs may need
      to focus on the highest cost cases in states where policy gives workers more
      control over the choice of provider, rather than the simpler and broader issue of
      whether policy gives workers or employers more control.

PMID- 30206936
TI  - Association between Continuity and Team-Based Care and Health Care Utilization:
      An Observational Study of Medicare-Eligible Veterans in VA Patient Aligned Care
      Team.
AB  - OBJECTIVE: It remains unknown whether high-functioning teams can compensate for
      poor continuity of care to support important patient outcomes. DATA SOURCE:
      Linked VA administrative and Medicare claims data to measure the relationship of
      team-based care and continuity of care with high-cost utilization. STUDY DESIGN:
      Retrospective cohort study of 1.2 million VA-Medicare dual eligible Veterans
      assigned to a VA primary care provider (PCP) in 2012. Continuity was the
      proportion of primary care visits to the assigned VA provider of care. Clinics
      were categorized as low, average, or high-team functioning based on survey data.
      Our primary outcomes were the number of all-cause hospitalizations, ambulatory
      care sensitive (ACSC) hospitalizations, and emergency department (ED) visits in
      2013. PRINCIPAL FINDINGS: A 10-percentage point increase in continuity with a VA
      PCP was associated with 4.5 fewer hospitalizations (p < .001), 3.2 fewer ACSC
      hospitalizations (p < .001), and 2.6 more ED visits (p = .07) per 1,000 patients.
      Team-based care was not significantly associated with any high-cost utilization
      category. Associations were heterogeneous across VA-reliant and nonreliant
      Veterans. Finally, the interaction results demonstrated that the quality of team
      based care functioning could not compensate for poor continuity on
      hospitalizations, ACSC hospitalizations, or ED visits. CONCLUSIONS: In Veterans
      who were reliant on the VA for services, increasing continuity with a VA PCP and
      high-functioning team-based care clinics was associated with fewer ED visits and
      hospitalizations. Furthermore, leveraging combined data from VA and Medicare
      allowed to better measure continuity and assess high-cost utilization among
      Veterans who are and are not reliant on the VA for services.

PMID- 30206937
TI  - Safety and efficacy of neoadjuvant chemotherapy containing bevacizumab and
      interval debulking surgery for advanced epithelial ovarian cancer: A feasibility
      study.
AB  - BACKGROUND AND OBJECTIVES: The optimum treatment strategy for patients with
      unresectable advanced epithelial ovarian cancer is controversial. This study
      examined bevacizumab combined with neoadjuvant chemotherapy (NAC; paclitaxel plus
      carboplatin), followed by interval debulking surgery (IDS), for these patients.
      METHODS: In a prospective nonrandomized study, newly diagnosed patients received
      four cycles of NAC (three cycles combined with bevacizumab), followed by IDS. The
      primary endpoint was the complete resection rate at IDS. Secondary endpoints were
      the NAC response rate, adverse events during NAC, and perioperative
      complications. RESULTS: Twenty-three patients were enrolled. The complete
      resection rate at IDS was 60.9% (95% confidence intervals [CI]: 38.5% to 80.3%).
      The NAC response rate was 86.9% (95% CI: 66.4% to 97.2%). Adverse events >= grade
      3 during NAC were neutropenia (78.3%), anemia (52.2%), hypertension (17.4%), and
      proteinuria (8.7%). There was no thromboembolism or gastrointestinal perforation.
      Grade 2 complications of IDS included lymphatic complications (13.6%), infections
      (9.1%), ileus (4.5%), and wound dehiscence (4.5%). There were no thromboembolic
      complications, fistula/abscess, or perforation/anastomotic leak, and no
      complications >= grade 3. CONCLUSIONS: In Japanese patients with advanced ovarian
      cancer, bevacizumab + NAC followed by IDS is an acceptable strategy. Further
      investigation of its prognostic effect is warranted.

PMID- 30206939
TI  - Implementation of interventions informed by precursor functional analyses with
      young children: A replication.
AB  - Individuals who engage in problem behavior may also engage in precursor behavior
      maintained by the same functional reinforcers as the more severe target problem
      behavior. This study replicates and extends previous research by examining
      precursor assessments and interventions with three preschool-aged children. We
      conducted assessments to identify precursor behavior, and conducted subsequent
      functional analyses targeting the precursor behavior. We then implemented
      function-based interventions to address the precursor behavior, resulting in
      reductions in precursor behavior and continued low or zero rates of severe
      problem behavior.

PMID- 30206940
TI  - Nerve repair and regeneration: Biological tubulization limits and future
      perspectives.
AB  - Peripheral nerve physiology and regeneration has been observed and investigated
      in literature but surgical applications to reconstruct and restore motor or
      sensory functions are still in a developmental phase. The peripheral nerve
      progresses slowly and incompletely compared with other tissues, it may provoke
      separations of the nerve stumps and the axonal proliferation of the conduits is
      restricted to 30 mm. Recent surgical attempts to treat proximal nerve injures
      include direct nerve restoration, transfer, and autografting measures with
      favorable results. Moreover, studies are suggesting that engineering tissue tubes
      maybe as effective as nerve grafting to restore separations of more than 4 cm
      toward optimal nerve repair.

PMID- 30206941
TI  - Sex differences in personality are larger in gender equal countries: Replicating
      and extending a surprising finding.
AB  - Sex differences in personality have been shown to be larger in more gender equal
      countries. We advance this research by using an extensive personality measure,
      the IPIP-NEO-120, with large country samples (N > 1000), from 22 countries.
      Furthermore, to capture the multidimensionality of personality we measure sex
      differences with a multivariate effect size (Mahalanobis distance D). Results
      indicate that past research, using univariate measures of effect size, have
      underestimated the size of between-country sex differences in personality.
      Confirming past research, there was a strong correlation (r = .69) between a
      country's sex differences in personality and their Gender Equality Index.
      Additional analyses showed that women typically score higher than men on all five
      trait factors (Neuroticism, Extraversion, Openness, Agreeableness and
      Conscientiousness), and that these relative differences are larger in more gender
      equal countries. We speculate that as gender equality increases both men and
      women gravitate towards their traditional gender roles.

PMID- 30206942
TI  - Intraorganismal genetic heterogeneity as a source of genetic variation in modular
      macroalgae.
AB  - Genetic diversity is considered a key factor of population survival and
      evolution, especially in changing environments. Genetic diversity arises from
      mutations in the DNA sequence of cell lines and from there it reaches the level
      of organisms, populations, and regions. However, many previous studies have not
      considered the organism architecture or pattern of thallus construction, ignoring
      the potential genetic complexities that intraorganismal genetic heterogeneity
      could generate in modular organisms. In seaweeds, modularity and clonality exist
      in many species. Modular organization has been related to advantages in terms of
      rapid construction and recovery after the loss of individual modules, which have
      their own demographic properties as they generate, mature, senesce, and die.
      Based on recent evidence from the literature, we suggest that modules also have
      their own genetic properties. Specifically, modular seaweeds have two possible
      sources of genetic diversity at the individual level: the heterozygosity of the
      genotypes composing the genet, and genetic heterogeneity among the modules within
      a genet (i.e., intraclonal genetic variability). Both sources of genetic
      diversity can have ecological and evolutionary consequences, and most of them
      must be considered in research on modular seaweeds. Linking intraorganismal
      genetic diversity with clonal architecture and propagation styles may help us to
      understand important ecological and evolutionary processes such as speciation
      modes, invasive capacities, or farming potential.

PMID- 30206938
TI  - TRPV1 and BDKRB2 receptor polymorphisms can influence the exercise pressor
      reflex.
AB  - KEY POINTS: The mechanisms responsible for the high inter-individual variability
      in blood pressure responses to exercise remain unclear. Common genetic variants
      of genes related to the vascular transduction of sympathetic outflow have been
      investigated, but variants influencing skeletal muscle afferent feedback during
      exercise have not been explored. Single nucleotide polymorphisms in TRPV1
      rs222747 and BDKRB2 rs1799722 receptors present in skeletal muscle were
      associated with differences in the magnitude of the blood pressure response to
      static handgrip exercise but not mental stress. The combined effects of TRPV1
      rs222747 and BDKRB2 rs1799722 on blood pressure and heart rate responses during
      exercise were additive, and primarily found in men. Genetic differences in
      skeletal muscle metaboreceptors may be a risk factor for exaggerated blood
      pressure responses to exercise. ABSTRACT: Exercise blood pressure (BP) responses
      demonstrate high inter-individual variability, which could relate to differences
      in metabolically sensitive afferent feedback from the exercising muscle. We
      hypothesized that single-nucleotide polymorphisms (SNPs) in genes encoding
      metaboreceptors present in group III/IV skeletal muscle afferents can influence
      the exercise pressor response. Two hundred men and women underwent measurements
      of continuous BP and heart rate at baseline and during 2 min of static handgrip
      exercise (30% maximal volitional contraction), post-exercise circulatory
      occlusion and mental stress (serial subtraction; internal control). Participants
      were genotyped for SNPs in TRPV1 (rs222747; G/C), ASIC3 (rs2288645; G/A), BDKRB2
      (rs1799722; C/T), PTGER2 (rs17197; A/G) and P2RX4 (rs25644; A/G). Exercise
      systolic BP (19 +/- 10 vs. 22 +/- 10 mmHg, P = 0.03) was lower in GG versus GC/CC
      minor allele carriers for TRPV1 rs222747, while exercise diastolic BP (14 +/- 7
      vs. 17 +/- 7 mmHg, P = 0.007) and heart rate (12 +/- 8 vs. 15 +/- 9 beats min-1 ,
      P = 0.03) were lower in CC versus CT/TT minor allele carriers for BDKRB2
      rs1799722. Individuals carrying both minor alleles for TRPV1 rs222747 and BDKRB2
      rs1799722 had greater systolic (22 +/- 11 vs. 17 +/- 10 mmHg, P = 0.04) and
      diastolic (18 +/- 7 vs. 14 +/- 7 mmHg, P = 0.01) BP responses than those with no
      minor alleles; these differences were larger in men. No differences in BP or
      heart rate responses were detected during static handgrip with ASIC3 rs2288645,
      PTGER2 rs17197 or P2RX4 rs25644. None of the selected SNPs were associated with
      differences during mental stress. These findings demonstrate that variants in
      TRPV1 and BDKRB2 receptors can contribute to BP differences during static
      exercise in an additive manner.

PMID- 30206943
TI  - Cerebroprotective effects of hydrogen sulfide in homocysteine-induced
      neurovascular permeability: Involvement of oxidative stress, arginase, and matrix
      metalloproteinase-9.
AB  - An elevated level of homocysteine (Hcy) leads to hyperhomocysteinemia (HHcy),
      which results in vascular dysfunction and pathological conditions identical to
      stroke symptoms. Hcy increases oxidative stress and leads to increase in blood
      brain barrier permeability and leakage. Hydrogen sulfide (H2 S) production during
      the metabolism of Hcy has a cerebroprotective effect, although its effectiveness
      in Hcy-induced neurodegeneration and neurovascular permeability is less explored.
      Therefore, the current study was designed to perceive the neuroprotective effect
      of exogenous H 2 S against HHcy, a cause of neurodegeneration. To test this
      hypothesis, we used four groups of mice: control, Hcy, control + sodium
      hydrosulfide hydrate (NaHS), and Hcy + NaHS, and an HHcy mice model in Swiss
      albino mice by giving a dose of 1.8 g of dl-Hcy/L in drinking for 8-10 weeks.
      Mice that have 30 umol/L Hcy were taken for the study, and a H 2 S
      supplementation of 20 MUmol/L was given for 8 weeks to all groups of mice. HHcy
      results in the rise of the levels of superoxide and nitrite, although a
      concomitant decrease in the level of superoxide dismutase, catalase, glutathione
      peroxidase, reduced glutathione, and arginase in oxidative stress and a
      concomitant decrease in the endogenous level of H 2 S. Although H 2 S
      supplementation ameliorated, the effect of HHcy and the levels of H 2 S returned
      to the average level in HHcy animals supplemented with H 2 S. Interestingly, H 2
      S supplementation ameliorated neurovascular remodeling and neurodegeneration.
      Thus, our study suggested that H 2 S could be a beneficial therapeutic candidate
      for the treatment of Hcy-associated neurodegeneration, such as stroke and
      neurovascular disorders.

PMID- 30206944
TI  - A balanced time perspective: Is it an exercise in empiricism, and does it relate
      meaningfully to health and well-being outcomes?
AB  - Time perspective research assesses the degree to which thoughts and feelings
      about the past, present and future influence behaviour, and a balanced time
      perspective profile has been posited as being ideal. Although this area of
      research has seen a move towards person-centred analyses, using either cluster
      analyses or a deviation from balanced time perspective (DBTP) approach, there are
      a number of theoretical and methodological issues that must be addressed. Using
      data from diverse samples in four countries, the present study used both cluster
      analyses and the DBTP approach to assess how cluster membership and DBTP scores
      related to a range of health and well-being outcomes. As in previous studies, a
      balanced profile only emerged once in cluster analyses, and positive-oriented
      profiles were associated with optimal outcomes. The study also found evidence of
      a relationship between DBTP scores and scores on well-being indicators. However,
      results gained after manipulating the DBTP equation in two different ways again
      indicated that higher than expected positive past and present or past and future
      scores were responsible for the positive outcomes. As such, these findings raise
      concerns regarding the use of the DBTP construct within clinical settings.

PMID- 30206947
TI  - Plant antimicrobial polyphenols as potential natural food preservatives.
AB  - BACKGROUND: The growing demand for natural food preservatives in the last decade
      has promoted investigations on their application for preserving perishable foods.
      In this context, the present review is focused on discussing the prospective
      application of plant extracts containing phenolics or isolated plant phenolics as
      natural antimicrobials in foods. Plant essential oils are outside the scope of
      this review since utilization of their antimicrobial activity for food
      preservation has been extensively reviewed. RESULTS: Although the exact
      antimicrobial mechanisms of action of phenolic compounds are not yet fully
      understood, it is commonly acknowledged that they have diverse sites of action at
      the cellular level. Antimicrobial phenolics can be added directly to the
      formulation of perishable food products or incorporated into food-contact
      materials to release them in the immediate zone of perishable foods. Edible
      coatings or active food packaging materials can thus be used as carriers of plant
      bioactive compounds. CONCLUSION: These materials could be an interesting delivery
      system to improve the stability of phenolics in foods and to improve the shelf
      life of perishable foods. This review will thus provide an overview of current
      knowledge of the antimicrobial activity of phenolic-rich plant extracts and of
      the promises and limits of their exploitation for the preservation of perishable
      foods. (c) 2018 Society of Chemical Industry.

PMID- 30206945
TI  - Complex and spatially segregated auditory inputs of the mouse superior
      colliculus.
AB  - KEY POINTS: Although the visual circuits in the superior colliculus (SC) have
      been thoroughly examined, the auditory circuits lack equivalent scrutiny. SC
      neurons receiving auditory inputs in mice were characterized and three
      distinguishable types of neurons were found. The auditory pathways from external
      nuclei of the inferior colliculus (IC) were characterized, and a novel direct
      inhibitory connection and an excitation that drives feed-forward inhibitory
      circuits within the SC were found. The direct excitatory and inhibitory inputs
      exhibited distinct arbourization patterns in the SC. These findings suggest
      functional differences between excitatory and inhibitory sensory information that
      targets the auditory SC. ABSTRACT: The superior colliculus (SC) is a midbrain
      structure that integrates auditory, somatosensory and visual inputs to drive
      orientation movements. While much is known about how visual information is
      processed in the superficial layers of the SC, little is known about the SC
      circuits in the deep layers that process auditory inputs. We therefore
      characterized intrinsic neuronal properties in the auditory-recipient layer of
      the SC (stratum griseum profundum; SGP) and confirmed three
      electrophysiologically defined clusters of neurons, consistent with literature
      from other SC layers. To determine the types of inputs to the SGP, we expressed
      Channelrhodopsin-2 in the nucleus of the brachium of the inferior colliculus
      (nBIC) and external cortex of the inferior colliculus (ECIC) and optically
      stimulated these pathways while recording from SGP neurons. Probing the
      connections in this manner, we described a monosynaptic excitation that
      additionally drives feed-forward inhibition via circuits intrinsic to the SC.
      Moreover, we found a profound long-range monosynaptic inhibition in 100% of
      recorded SGP neurons, a surprising finding considering that only about 15% of SGP
      projecting neurons in the nBIC/ECIC are inhibitory. Furthermore, we found spatial
      differences in the cell body locations as well as axon trajectories between the
      monosynaptic excitatory and inhibitory inputs, suggesting that these inputs may
      be functionally distinct. Taking this together with recent anatomical evidence
      suggesting an auditory excitation from the nBIC and a GABAergic multimodal
      inhibition from the ECIC, we propose that sensory integration in the SGP is more
      multifaceted than previously thought.

PMID- 30206948
TI  - Systematic review with meta-analysis: conditioned pain modulation in patients
      with the irritable bowel syndrome.
AB  - BACKGROUND: Irritable bowel syndrome (IBS) is common and is characterised by
      recurrent abdominal pain, which is a major contributor to healthcare seeking. The
      neurobiological basis of this pain is incompletely understood. Conditioned pain
      modulation is a neuromodulatory mechanism through which the brain inhibits the
      nociceptive afferent barrage through the descending pathways. Reduced conditioned
      pain modulation has been implicated in the pathophysiology of IBS, although to
      date only in studies with relatively small sample sizes. AIM: To clarify the
      relationship between conditioned pain modulation and IBS by undertaking a
      systemic review and meta-analysis METHODS: A systematic review of MEDLINE and Web
      of Science databases was searched (up to 10 May 2018). We included studies
      examining conditioned pain modulation in adults with IBS and healthy subjects.
      Data were pooled for meta-analysis to calculate the odds ratio and effect size of
      abnormal conditioned pain modulation in IBS, with 95% confidence intervals (CI).
      RESULTS: The search strategy identified 645 studies, of which 13 were relevant
      and 12 met the inclusion criteria. Conditioned pain modulation in IBS patients vs
      healthy subjects was significantly reduced, odds ratio 4.84 (95% CI: 2.19-10.71,
      P < 0.0001), Hedges' g effect size of 0.85 (95% CI: 0.42-1.28, P < 0.001). There
      was significant heterogeneity in effect sizes (Q-test chi2 = 52, P < 0.001, I2 =
      78.8%) in the absence of publication bias. CONCLUSION: Conditioned pain
      modulation is significantly diminished in patients with IBS vs healthy controls.
      These data suggest that abnormal descending pathways may play an important
      pathophysiological role in IBS, which could represent an investigation and a
      therapeutic target in IBS.

PMID- 30206949
TI  - Elastography as a diagnostic tool in the prostate tumour detection in Labrador
      retriever.
AB  - Prostate tumours are hard to detect in dogs. Early diagnosis is a key to maintain
      fertility and to protect against metastasis and death. Elastography is a
      diagnostic tool to obtain very detailed results of changes in tissue stiffness of
      this organ. There are no studies about the application of elastography to
      diagnose the prostate tumours in dogs. In our case, in male Labrador retriever
      there was state a prostate lesion by both scanning-grey ultrasonogram and
      elastography. Fine needle aspiration biopsy (FNA) confirmed the adenocarcinoma
      only in elastography-changed area. Thus, this method is helpful to diagnose
      prostate tumours and should be the first additional survey in routine examination
      of the prostate in the dog.

PMID- 30206950
TI  - Statistical inferences of extended concentration indices for directly
      standardized rates.
AB  - The relative concentration index (RCI) and the absolute concentration index (ACI)
      have been widely used for monitoring health disparities with ranked health
      determinants. The RCI has been extended to allow value judgments about inequality
      aversion by Pereira in 1998 and by Wagstaff in 2002. Previous studies of the
      extended RCI have focused on survey sample data. This paper adapts the extended
      RCI for use with directly standardized rates (DSRs) calculated from population
      based surveillance data. A Taylor series linearization (TL)-based variance
      estimator is developed and evaluated using simulations. A simulation-based Monte
      Carlo (MC) variance estimator is also evaluated as a comparison. Following
      Wagstaff's approach in 1991, we extend the ACI for use with DSRs. In all
      simulations, both the TL and MC methods produce valid variance estimates. The TL
      variance estimator has a simple, closed form that is attractive to users without
      sophisticated programming skills. The TL and MC estimators have been incorporated
      into a beta version of the National Cancer Institute's Health Disparities
      Calculator, a free statistical software tool that enables the estimation of 11
      commonly used summary measures of health disparities for DSRs.

PMID- 30206951
TI  - Nonmedical prescriber experiences of training and competence to report adverse
      drug reactions in the UK.
AB  - WHAT IS KNOWN AND OBJECTIVE: Adverse drug reaction reporting in the UK is lower
      than expected based on epidemiological data. This study aims to explore (a)
      nonmedical prescribers' (NMP) confidence in identifying and reporting ADRs, (b)
      NMP prescribing habits and engagement with the Yellow Card Scheme (YCS) and (c)
      NMP desire for future training in the identification and reporting of ADRs.
      METHODS: A survey was distributed across NMP networks in the north-west of
      England using Survey Monkey. Univariate analyses were performed to compare the
      features of reporters and nonreporters, Kruskal-Wallis H tests for comparisons
      within multiple subgroups and Spearman's rank correlation coefficient for
      response associations between answers to ordered-category questions. RESULTS AND
      DISCUSSION: A total of 570 responses were available for analysis, an estimated
      response rate of 20%. Less than half (n = 219; 38.4%) reported submitting a
      Yellow Card to the YCS, and the majority of those individuals have submitted five
      or less Yellow Cards; 28 responders reported more than five submissions. Being
      professionally qualified for more years (linear regression: B = 0.30, P < 0.0005;
      95% CI 1.01 to 1.05) and receiving additional training support about the YCS (chi
      squared: chi2  = 14.7, P < 0.0005) were associated with an increased likelihood
      of submitting to the YCS. There was a positive linear relationship between
      confidence in identifying ADRs and likelihood of reporting to YCS. The most
      common reason given (n = 261) for never having reported to the YCS was "I have
      never seen an adverse drug reaction." Training appears to give NMPs confidence in
      reporting ADRs, but there seems to be a gap in actually identifying ADRs given
      the comment that most had never seen an ADR. WHAT IS NEW AND CONCLUSION:
      Strategies for improving the translation of theoretical knowledge about ADRs into
      practical skills in identifying ADRs, and subsequently reporting them, will be
      important for improving pharmacovigilance practice.

PMID- 30206952
TI  - Comparison of non-volatile and volatile flavor compounds in six Pleurotus
      mushrooms.
AB  - BACKGROUND: Non-volatile and volatile flavor compounds of six Pleurotus mushrooms
      including Pleurotus citrinopileatus, P. cornucopiae, P. djamor, P. floridanus, P.
      ostreatus and P. sapidus were studied. RESULTS: The content of total free amino
      acids ranged from 21.80 to 40.60 g kg-1 and the content of monosodium glutamate
      (MSG)-like amino acids ranged from 3.10 to 8.64 g kg-1 . The content of total 5'
      nucleotides ranged from 4.16 to 8.80 g kg-1 while the content of flavor 5'
      nucleotides ranged from 2.00 to 4.51 g kg-1 . Sixty-three volatile compounds were
      identified in six Pleurotus mushrooms, including 17 aldehydes, 10 ketones, 14
      alcohols, 2 ethers, 5 acids, 5 hydrocarbons, 10 heterocyclic and aromatic
      compounds. 1-Octen-3-one and 1-octen-3-ol were the key odor compounds in P.
      citrinopileatus, P. djamor, P. ostreatus, P. floridanus and P. sapidus, while 1
      octen-3-one, 1-octen-3-ol and 2-octenal were the key odor compounds in P.
      cornucopiae. CONCLUSION: Pleurotus citrinopileatus had highest content of total
      free amino acids (40.60 g kg-1 ), total 5'-nucleotides (8.80 g kg-1 ) and flavor
      5'-nucleotides (4.51 g kg-1 ) than other Pleurotus mushrooms. Moreover, eight
      carbon compounds were the most abundant compounds in six Pleurotus mushrooms. Our
      study should be helpful in promoting the cultivation and consumption of these
      Pleurotus mushrooms. (c) 2018 Society of Chemical Industry.

PMID- 30206953
TI  - Plasma Unesterified Fatty-Acid Profile Is Dramatically and Acutely Changed under
      Ischemic Stroke in the Mouse Model.
AB  - Although plasma biomarkers would facilitate rapid and accurate diagnosis of
      ischemic stroke for immediate treatment, no such biomarkers have been developed
      to date. In the present study, we tested our hypothesis that plasma unesterified
      fatty acids (FFA) are altered at early stages of acute ischemic stroke. Plasma
      was collected from mice 2 h after the permanent middle cerebral artery occlusion
      (pMCAo) onset, as well as from sham operated and control animals. After 2 h,
      pMCAo significantly changed the plasma FFA profile with the most dramatic 2- to 3
      fold relative increase in very long n-3 and n-6 FFA including 20:4n-6, 22:4n-6,
      22:5n-6, and 22:6n-3. Changes in the plasma FFA profile are consistent with FFA
      liberation from brain phospholipid hydrolyzed under ischemic insult. These
      results identify, for the first time, the plasma FFA profile as a potential
      biomarker for an early ischemic stroke within the therapeutic window for
      thrombolytic treatment. Further studies are required to confirm its specificity
      and sensitivity in clinical settings.

PMID- 30206955
TI  - Developing Predictive Models to Enhance Clinician Prediction of Suicide Attempts
      Among Veterans With and Without PTSD.
AB  - : The limitations of self-report confine clinicians' ability to accurately
      predict suicides and suicide attempts (SAs). Behavioral assessments (e.g., Death
      Implicit Association Test [IAT]) may be a means of supplementing self-report and
      clinician prediction. OBJECTIVE: The authors aimed to build and test a predictive
      model of SAs that included established risk factors and measures of suicide risk,
      and Death IAT scores. The authors also sought to test the predictive validity of
      the SA model among subgroups of Veterans with and without PTSD. METHOD:
      Participants included 166 psychiatrically hospitalized Veterans. RESULTS: A model
      that included patient prediction, age, and Death IAT scores improved upon
      clinician prediction of SAs during the six-month follow-up (C-statistic for
      clinician prediction = 73.6, 95% CI [62.9, 84.4] and C-statistic for model =
      82.8, 95% CI [74.6, 91.0]). The model was tested in subgroups of Veterans with
      and without PTSD. Among Veterans without PTSD, the Death IAT and patient
      prediction predicted SAs above and beyond clinician prediction, while these
      variables did not significantly improve prediction among Veterans with PTSD (C
      statistic for no-PTSD = 91.3, 95% CI [80.6, 1.00]; C-statistic for PTSD = 86.8,
      95% CI [76.8, 96.8]). Building a separate model for Veterans with PTSD did not
      improve upon clinician prediction. CONCLUSIONS: Findings indicate that predictive
      models may bolster clinician prediction of SAs and that predictors may differ for
      Veterans with PTSD.

PMID- 30206956
TI  - Graphing the Win Ratio and its components over time.
AB  - Clinical trials are often designed to compare treatments on the basis of multiple
      outcomes. For the analysis of the treatment comparison from such a trial, in
      1999, the Finkelstein-Schoenfeld test was proposed, which was a generalization of
      the Gehan-Wilcoxon test based on pairwise comparison of patients on a primary
      outcome when possible but otherwise on a secondary outcome. In 2012, Pocock and
      colleagues suggested an estimate based on this concept, the Win Ratio, which
      summarized the ratio of the number of patients who fared better versus worse on
      the experimental arm. However, in 2016, Oakes noted that the Win Ratio could be a
      function of the distribution of follow-up times of the trial. The aim of this
      paper is to propose an approach to representing the Win Ratio graphically in such
      a way that the effect of time on the estimate would be apparent. In addition, the
      methods are used to display the contribution of each endpoint to the composite.
      We apply the methods to clinical trials in cancer, cardiology, and neurology.
      Software is available named winRatioAnalysis in CRAN.

PMID- 30206954
TI  - Adverse cutaneous reactions to skin care products on the face vary with age, but
      not with sex.
AB  - BACKGROUND: Adverse skin reactions to skin care products have been increasing in
      recent years. However, to date, these reactions have not been well characterized.
      OBJECTIVE: To describe the symptoms, clinical signs and frequency of adverse
      cutaneous reactions to skin care products on the face in males vs females of
      various ages. PATIENTS AND METHODS: All outpatients diagnosed with adverse
      cutaneous reactions to skin care products on the face examined by dermatologists
      at the Dermatology Hospital of South Medical University between November 1, 2016
      and October 31, 2017, employing a questionnaire and an interview, were eligible.
      The associations of adverse cutaneous reactions with age and sex were analysed.
      RESULTS: A total of 433 outpatients, accounting for 0.12% of all outpatients,
      were assessed. Of these, 223 patients, including 204 females and 19 males, aged 4
      to 75 years, were eventually diagnosed with adverse reactions to skin care
      products on the face. Eighty-two per cent of patients experienced pruritus, 80%
      showed erythema, and 48% showed visible swelling. The incidence rates of both
      xerosis and oedema correlated positively with age, whereas acne-like lesions were
      negatively associated with age, but not with sex. CONCLUSIONS: Our results
      indicate that pruritus, xerosis and erythema are common adverse cutaneous
      reactions to facial skin care products. These reactions vary with age, but not
      with sex. Vigorous safety testing should precede the marketing of skin care
      products.

PMID- 30206957
TI  - Spotting Zika spots: descriptive features of the rash used in 66 published cases.
AB  - Zika virus (ZV) is an important emerging infection. Rash is a key feature, but
      the summative literature lacks description of the rash beyond 'maculopapular'.
      Our aim was to identify the cutaneous features described in the published
      literature. A literature search using defined terms for ZV cases reports and
      series was performed on the OVID, Clinical Key and University of Dundee's e
      library journals databases in December 2016; a later case report was included
      while the paper was under review. Diagnosis in all cases was via PCR. Exclusion
      criteria were Zika cases without rash or omitting any description of the rash.
      Ocular features (conjunctivitis) were not included. In total, 42 publications
      with 66 cases met the criteria. The most frequent descriptive features included
      maculopapular (59%), lower limb petechial purpura (11%) and erythematous/red
      (9%). Pruritus was described in 44% and tenderness in 3%. Lesions were located on
      the trunk (29%), limbs (5% arms, 11% both arms and legs), face (17%) and
      extremities (14%) or were diffuse/generalized (12%). There was facial sparing in
      3%. Other features were centrifugal spread (6%), palmar and/or plantar
      involvement (6%), palmoplantar desquamation (2%) and malar erythema with oedema
      (2%). Mucosal features included gingival bleeding (11%), oral haemorrhagic
      blisters (8%) and painful blisters/vesicles (4%). Oedema/swelling was described
      in the upper limbs (5%), lower limbs (5%) and both (3%). Mean rash duration was 6
      days (range 3-11 days). The ZV exanthema is most frequently maculopapular,
      pruritic, sometimes with centrifugal spread from the trunk to extremities. This
      may include lower limb petechial purpura, palmoplantar lesions, oedema of limb
      extremities, and gingival bleeding or painful oral bullae. As ZV becomes more
      prevalent, recognition of the clinical features will enable earlier diagnosis and
      appropriate testing.

PMID- 30206958
TI  - Sphingolipidomics of Thermotolerant Yeasts.
AB  - Mass spectrometry-based shotgun lipidomics was applied to the analysis of
      sphingolipids of 11 yeast strains belonging to four genera, that is Cryptococcus,
      Saccharomyces, Schizosaccharomyces, and Wickerhamomyces. The analysis yielded
      comprehensive results on both qualitative and quantitative representation of
      complex sphingolipids of three classes-phosphoinositol ceramide (PtdInsCer),
      mannosyl inositol phosphoceramide (MInsPCer), and mannosyl diinositol
      phosphoceramide (M(InsP)2 Cer). In total, nearly 150 molecular species of complex
      sphingolipids were identified. Individual strains were cultured at five different
      temperatures, that is 5, 10, 20, 30, and 40  degrees C (Wickerhamomyces genus
      only up to 30  degrees C), and the change in the culture temperature was found to
      affect the representation of both the sphingolipid classes and the length of the
      long-chain bases (LCB). Individual classes of sphingolipids differing in polar
      heads differed in the temperature response. The relative content of PtdInsCer
      increased with increasing temperature, whereas that of M(InsP)2 Cer decreased.
      Molecular species having C18-LCB were associated with low cultivation
      temperature, and a higher proportion of C20-LCB molecular species was produced at
      higher temperatures regardless of the type of polar head. On the other hand, the
      influence of temperature on the representation of very long-chain fatty acids
      (VLCFA) was less noticeable, the effect of the taxonomic affiliation of the
      strains being more pronounced than the cultivation temperature. For example,
      lignoceric and 2-hydrocylo-lignoceric acids were characteristic of the genera
      Cryptococcus and Schizosaccharomyces, and of Saccharomyces genus cultivated at
      high temperatures.

PMID- 30206960
TI  - Surgical management of marginal tears/avulsions of the suspensory ligament
      branches in 29 Thoroughbred racehorses.
AB  - BACKGROUND: Suspensory ligament branch injuries are common in horses. Most of
      these injuries are grouped together and considered as a single pathologic entity.
      OBJECTIVES: To report a specific injury of the abaxial margin of the suspensory
      ligament branches and to report its surgical management and outcome. STUDY
      DESIGN: Retrospective case series. METHODS: All horses with suspensory ligament
      branch injuries over a 9-year period (2007-2015) were identified. Horses with
      injuries which, on ultrasonographic examination, appeared to have defects in the
      abaxial margin of the suspensory ligament branch, that were subsequently
      confirmed during surgery were selected. RESULTS: Twenty-nine cases fulfilled the
      inclusion criteria with a specific lesion location on the abaxial margin of the
      suspensory ligament branch. Nineteen horses raced successfully after surgery,
      nine returned to training but failed to race and one was lost to follow-up. MAIN
      LIMITATIONS: The absence of a comparable population of non-surgically managed
      horses in this study means that the contribution of removing torn tissue cannot
      confidently be assessed. CONCLUSIONS: The location and morphology of injuries
      described in this study is consistent, which suggests aetiopathogenic
      commonality. This case series suggests this type of injury has an identity of its
      own, differs from other types of suspensory ligament branch injuries and
      represents a previously undescribed subgroup.

PMID- 30206959
TI  - Determination of optimum harvest maturity and non-destructive evaluation of pod
      development and maturity in cacao (Theobroma cacao L.) using a multiparametric
      fluorescence sensor.
AB  - BACKGROUND: A series of fluorescence indices (anthocyanin, flavonol, chlorophyll
      and nitrogen balance) were deployed to detect the pigments and colourless
      flavonoids in cacao pods of three commercial cacao (Theobroma cacao L.) genotypes
      (QH1003, KKM22 and MCBC1) using a fast and non-destructive multiparametric
      fluorescence sensor. The aim was to determine optimum harvest periods (either 4
      or 5 months after pod emergence) of commercial cacao based on fluorescence
      indices of cacao development and bean quality. RESULTS: As pod developed, cacao
      exhibited a rise with the peak of flavonol occurring at months 4 and 5 after pod
      maturity was initiated while nitrogen balance showed a decreasing trend during
      maturity. Cacao pods contained high chlorophyll as they developed but chlorophyll
      content declined significantly on pods that ripened at month 5. CONCLUSION: Cacao
      pods harvested at months 4 and 5 can be considered as commercially-ready as the
      beans have developed good quality and comply with the Malaysian standard on cacao
      bean specification. Thus, cacao pods can be harvested earlier when they reach
      maturity at month 4 after pod emergence to avoid germinated beans and over
      fermentation in ripe pods harvested at month 5. (c) 2018 Society of Chemical
      Industry.

PMID- 30206961
TI  - Effects of RNA interference-mediated E-selectin gene silencing on cell adhesion
      molecule expression and cell-cell adhesion in vascular endothelial cells in mice
      with immunologic contact urticaria.
AB  - Contact urticaria is recognized as the wheal and flare reaction at a site from
      direct contact with a chemical or protein agent. Ongoing studies have proposed
      that gene silencing may have a promising future in finding optimal treatment of a
      variety of disease; hence, the aim of the study was to investigate the effect of
      RNA interference-mediated E-selectin ( SELE) gene silencing on cell adhesion
      molecule expression and on cell-cell adhesion in vascular endothelial cells
      (VECs) in a mouse model of immunologic contact urticaria (ICU). Following the
      successful establishment of mouse models of ICU induced by antidinitrophenol
      immunoglobulin E (IgE) combining 2,4-dinitrofluorobenzene challenge, enzyme
      linked immunosorbent assay and immunohistochemistry were used to measure the
      levels of IgE, interleukin 4 (IL-4), interferon-gamma (IFN-gamma), and histamine
      as well as the positive expression rate of SELE, respectively. The siRNA- SELE
      vector was constructed and transfection efficiency was estimated prior to
      performing quantitative reverse-transcription polymerase chain reaction and
      Western blot assay to determine the relative expression of SELE, eosinophil
      cationic protein (ECP), intercellular adhesion molecule 1 (ICAM-1), L-selectin
      (CD62L), and the alpha chain of leukocyte function-associated antigen-1 (CD11a).
      Adhesion assay was then performed to assess the cell adhesion ability in VECs.
      Elevated levels of IgE, IL-4, IFN-gamma, and histamine and increased positive
      expression rate of SELE were indicative of successful establishment of mouse
      models of ICU. Furthermore, the relative expression levels of SELE, ECP, ICAM-1,
      CD62L, and CD11a were highest in the OE- SELE group. Besides, cell adhesion
      ability of VECs was notably promoted. Collectively, the current study define the
      potential role of SELE silencing as an inhibitor to ICU development by inhibiting
      cell adhesion ability of VECs.

PMID- 30206962
TI  - MiR-490-5p inhibits the stemness of hepatocellular carcinoma cells by targeting
      ECT2.
AB  - To explore the targeting relationship between miR-490-5p and ECT2 in
      hepatocellular carcinoma (HCC) and the influences of miR-490-5p and ECT2 on the
      stemness of HCC cells. The expressions of miR-490-5p and ECT2 in HCC tissues and
      adjacent tissues were identified by quantitative real-time polymerase chain
      reaction (qRT-PCR). The relationships between the expression levels of miR-490
      5p/ ECT2 and the overall/disease-free survival (OS/DFS) of patients with HCC were
      evaluated using correlative curves. In addition, the targeting relationship
      between miR-490-5p and ECT2 was predicted by TargetScan and verified by dual
      luciferase reporter assay. Plasmid transfection was used for overexpression of
      ECT2 in HepG2 cells, and transfection efficiency was verified by qRT-PCR. Cell
      Counting Kit-8 assay and cell sphere-formation assay were conducted to detect the
      proliferation and sphere-formation ability of HCC cells, respectively. Cell
      populations with different cell transfections were sorted using flow cytometry.
      The expression levels of proteins in the stem cell signaling pathway were
      determined using Western blot analysis. MiR-490-5p was remarkably downregulated,
      yet ECT2 was upregulated in HCC tissues compared with adjacent tissues. MiR-490
      5p expression was positively correlated with OS and DFS of patients with HCC,
      which were otherwise negatively correlated with ECT2 expression. ECT2 was
      validated to be the downstream target of miR-490-5p. Overexpression of miR-490-5p
      restrained the sphere formation ability, stemness, and proliferation of HCC
      cells. MiR-490-5p repressed the stemness of HCC cells through inhibiting the
      expression of ECT2. MiR-490-5p may be an underlying therapeutic target in HCC
      treatment.

PMID- 30206963
TI  - Insights into the role of d-amino acid oxidase mutations in amyotrophic lateral
      sclerosis.
AB  - Missense mutations in the coding region of d-amino acid oxidase (DAO) have been
      found in patients suffering from amyotrophic lateral sclerosis (ALS). Mutations
      primarily impair the enzymatic activity of DAO and cause neurodegeneration due to
      an abnormal accumulation of d-serine in the spinal cord. However, the structural
      and dynamic changes that lead to impaired enzymatic activity are not fully
      understood. We present here extensive molecular dynamics simulations of wild
      type, and all reported ALS-associated DAO mutants to elucidate the plausible
      mechanisms of impaired enzymatic activity, a critical function needed for
      neuroprotection. Simulation results show that DAO mutations disrupt several key
      interactions with the active site residues and decrease the conformational
      flexibility of active site loop comprising 216 to 228 residues, necessary for
      substrate binding and product release. This conformational restriction of the
      active site loop in the mutants is mainly due to the distortion of critical salt
      bridge and hydrogen bond interactions compared with wild-type. Furthermore,
      binding free energy calculations show that DAO mutants have a lower binding
      affinity toward cofactor flavin adenine dinucleotide and substrate imino-serine
      than the wild-type. A closer look at the cofactor and substrate interaction
      profiles further show that DAO mutants have lost several critical interactions
      with the neighboring residues as compared with wild-type. Taken together, this
      study provides first-hand explanation of crucial structural features that lead to
      the loss of enzymatic function in DAO mutants and highlights the need of further
      genomic scans of patients with ALS to map the association of novel DAO variants
      in ALS pathophysiology.

PMID- 30206964
TI  - Focal adhesion kinase, RhoA, and p38 mitogen-activated protein kinase modulates
      apoptosis mediated by angiotensin II AT2 receptors.
AB  - Apoptosis plays an important role in cellular processes such as development,
      differentiation, and homeostasis. Although the participation of angiotensin II
      (Ang II) AT2 receptors (AT 2 R) in cellular apoptosis is well accepted, the
      signaling pathway involved in this process is not well established. We evaluated
      the participation of signaling proteins focal adhesion kinase (FAK), RhoA, and
      p38 mitogen-activated protein kinase (p38MAPK) in apoptosis induced by Ang II via
      AT 2 R overexpressed in HeLa cells. Following a short stimulation time (120 to
      240 minutes) with Ang II, HeLa-AT 2 cells showed nuclear condensation, stress
      fibers disassembly and membrane blebbing. FAK, classically involved in
      cytoskeleton reorganization, has been postulated as an early marker of cellular
      apoptosis. Thus, we evaluated FAK cleavage, detected at early stimulation times
      (15 to 30 minutes). Apoptosis was confirmed by increased caspase-3 cleavage and
      enzymatic activity of caspase-3/7. Participation of RhoA was evaluated. HeLa-AT 2
      cells overexpressing RhoA wild-type (WT) or their mutants, RhoA V14
      (constitutively active form) or RhoA N19 (dominant-negative form) were used to
      explore RhoA participation. HeLa-AT 2 cells expressing the constitutively active
      variant RhoA V14 showed enhanced apoptotic features at earlier times as compared
      with cells expressing the WT variant. RhoA N19 expression prevented nuclear
      condensation/caspase activation. Inhibition of p38MAPK caused an increase in
      nuclear condensation and caspase-3/7 activation, suggesting a protective role of
      p38MAPK. Our results clearly demonstrated that stimulation of AT 2 R induce
      apoptosis with participation of FAK and RhoA while p38MAPK seems to play a
      prosurvival role.

PMID- 30206965
TI  - No evidence for a major effect of three common polymorphisms of the GPx1, MnSOD,
      and CAT genes on PCOS susceptibility.
AB  - AIM: Polycystic ovary syndrome (PCOS) is one of the prevalent endocrine-metabolic
      disorders. It is proposed that oxidative stress contributes to PCOS
      susceptibility and its metabolic associations. The current study aimed to
      investigate the influence of GPx1 (rs1050450), MnSOD (rs4880), and Catalase
      (rs1001179) variants with PCOS susceptibility, for the first time. METHODS: In a
      case-control study, 350 Kurdish female volunteers (175 PCOS patients and 175
      healthy controls) from Western Iran were studied. Genotyping for GPx1 and MnSOD
      were done using PCR-RFLP and for CAT the allele-specific PCR method was used.
      RESULTS: The percentage of patients suffering from hirsutism, acne, and
      acanthosis among patients with PCOS were 44.6%, 30.3%, and 14.9%, respectively.
      Distribution of alleles among patients suffering from PCOS versus healthy women
      was 'Pro' (69.1% vs 68.8%) and 'Leu' (31.4% vs 31.2%) for Gpx1, 'Ala' (61.43% vs
      56.57%) and 'Val' (38.57% vs 43.43%) for MnSOD, and 'C' (83.43% vs 84.57%) and
      'T' (16.57% vs 15.43%) for CAT. CONCLUSION: GPx1 (rs1050450), MnSOD (rs4880), and
      CAT (rs1001179) variants might not be a risk factor for PCOS.

PMID- 30206966
TI  - Forkhead box protein A1 confers resistance to transforming growth factor-beta
      induced apoptosis in breast cancer cells through inhibition of Smad3 nuclear
      translocation.
AB  - Transforming growth factor-beta (TGF-beta) induces apoptosis of normal epithelial
      cells, such as mammary epithelium. Although breast cancer progression associates
      with acquisition of resistance to TGF-beta-induced apoptosis, the molecular
      mechanisms underlying this resistance are largely unknown. Here, we show that
      forkhead box protein A1 (FOXA1), which is known as a pioneer transcription
      factor, suppresses TGF-beta-induced apoptosis of estrogen receptor-positive
      breast cancer cells. FOXA1 is found to inhibit nuclear translocation of Smad3, a
      key transcription factor downstream of TGF-beta signaling, through suppression of
      the binding of Smad3 to the nuclear import receptor importin7. Furthermore, RNA
      sequencing analyses show that knockdown of FOXA1 upregulates Smad3-mediated
      proapoptotic gene expression. These results demonstrate that FOXA1 as a potent
      survival factor that suppresses TGF-beta-induced apoptosis by inhibiting Smad3
      signaling in estrogen receptor-positive breast cancer cells. Thus, we provide
      evidence for the first time that FOXA1 localizing to the cytoplasm negatively
      regulates Smad3-induced apoptosis in TGF-beta-mediated signal transduction.

PMID- 30206967
TI  - Daphnetin inhibits RANKL-induced osteoclastogenesis in vitro.
AB  - Osteoporosis is a common orthopedic disease which is associated with hyper
      activated osteoclastogenesis. Daphnetin is a natural coumarin derivative isolated
      from Genus Daphne, which possesses antiarthritis effect. However, the role of
      daphnetin in osteoclastogenesis has not been illustrated. This study aimed to
      investigate the effects of daphnetin on receptor activator of NF-kappaB ligand
      (RANKL)-induced osteoclastogenesis in vitro. Our results showed that the
      osteoclast formation was significantly suppressed by daphnetin treatment in bone
      marrow-derived macrophages (BMMs), which was illustrated by reduced number of
      tartrate-resistant acid phosphatase positive multinucleated osteoclasts and
      decreased expression levels of tumor necrosis factor receptor-associated factors
      (TRAF6), c-Fos, nuclear factor of activated T cells c1, and cathepsin K. RANKL
      caused significant induction effects in reactive oxygen species (ROS) generation
      and nicotinamide adenine dinucleotide phosphate oxidase activity, whereas the
      induction was dramatically reduced after pretreatment with daphnetin. In
      addition, daphnetin prevented the RANKL-induced activation of NF-kappaB and
      Akt/GSK-3beta pathways in BMMs. These findings indicated that daphnetin exhibited
      an inhibitory effect on RANKL-induced osteoclastogenesis in vitro. The effect of
      daphnetin might be mediated by inhibiting ROS signal transduction, as well as
      preventing the activation of NF-kappaB and Akt/GSK-3beta signaling pathways.
      These findings indicated that daphnetin might be considered as a new therapeutic
      approach for the osteoporosis treatment.

PMID- 30206968
TI  - Inhibiting role of rosiglitazone in the regulation of inflammatory response and
      protective effects for severe acute pancreatitis in mice.
AB  - OBJECTIVES: Our study aimed to probe the effects of rosiglitazone treatment on a
      severe acute pancreatitis (SAP) model induced by caerulein and investigate the
      underlying mechanism. METHODS: Differentially expressed messenger RNAs (mRNAs) in
      the mice of a SAP group were screened out by microarray analysis. The
      inflammatory response pathway was obtained from the online website DAVID
      Bioinformatics Resources 6.8. The interactions of caerulein and its target
      proteins were shown by search tool for interactions of chemicals (STITCH).
      Functional interactions of the genes associated with pancreatitis and the target
      proteins of caerulein were obtained with search tool for interactions of
      chemicals (STRING). SAP mice were established by hourly intraperitoneal injection
      of caerulein. Rosiglitazone was used as treatment drug, and pancreatic
      inflammation was assessed. The expression of Socs3 was studied by reverse
      transcriptase-polymerase chain reaction (RT-PCR) and Western blot analysis. The
      expression of interleukin (IL)-6, IL-1b, and Egr1 were studied by RT-PCR and
      Western blot analysis. RESULTS: The GSE77983 data were analyzed, and the results
      showed that Socs3 was overexpressed in SAP tissues. The inflammation response
      pathway in pancreas was selected by DAVID, STITCH, and STRING. After injection of
      rosiglitazone in mice, the serum levels of amylase and lipase were decreased.
      Furthermore, the mRNA and protein levels of Socs3 and inflammatory cytokines in
      pancreatic tissues were downregulated. CONCLUSIONS: Rosiglitazone could protect
      mice with SAP from injury by downregulating Socs3 and inhibiting the inflammatory
      response pathway.

PMID- 30206969
TI  - Knockdown of USP28 enhances the radiosensitivity of esophageal cancer cells via
      the c-Myc/hypoxia-inducible factor-1 alpha pathway.
AB  - Acquired radioresistance is a major clinical obstacle in the treatment of
      esophageal cancer (EC). Ubiquitin-specific protease 28 (USP28) has been
      implicated in tumor growth in various cancer types. However, the role of USP28
      and its underlying mechanisms of radioresistance in EC remain unknown. In the
      current study, we found that USP28 and c-Myc levels were upregulated in EC
      tissues and EC cell lines. The mRNA expression levels of USP28 and c-Myc were
      increased in the radioresistant human EC cell line (ECA109R) compared with those
      in ECA109 cells. In addition, the expression levels of USP28 and c-Myc were
      increased with increase in culture time after irradiation. Meanwhile,
      overexpression of USP28 decreased the radiosensitivity of ECA109 cells. In
      contrast, USP28 knockdown enhanced the radiosensitivity of ECA109R cells.
      Moreover, USP28 positively regulated the protein level of c-Myc, and c-Myc
      negatively regulated the radiosensitivity of ECA109 and ECA109R cells.
      Furthermore, c-Myc reversed the inhibitory effect of USP28 on the
      radiosensitivity of EC cells. Additionally, c-Myc enhanced the accumulation of
      hypoxia-inducible factor-1 alpha (HIF-1alpha) at the posttranscriptional level,
      and the reinforcing effect of c-Myc silencing on the radiosensitivity of EC cells
      could be reversed by HIF-1alpha overexpression. Besides, knockdown of USP28
      blocked the effect of c-Myc on activation of ataxia telangiectasia-mutated/ataxia
      telangiectasia and Rad3-related DNA damage checkpoint after irradiation. In
      conclusion, knockdown of USP28 enhanced the radiosensitivity of EC cells by
      destabilizing c-Myc and enhancing the accumulation of HIF-1alpha. Therefore,
      USP28 may serve as a novel therapeutic target to overcome EC radioresistance.

PMID- 30206970
TI  - Acute physical exercise increases leptin-induced hypothalamic extracellular
      signal-regulated kinase1/2 phosphorylation and thermogenesis of obese mice.
AB  - The obesity is a result of energy imbalance and the increase in thermogenesis
      seems an interesting alternative for the treatment of this disease. The mechanism
      of energy expenditure through thermogenesis is tightly articulated in the
      hypothalamus by leptin. The hypothalamic extracellular signal-regulated kinase
      1/2 (ERK1/2) is a key mediator of the thermoregulatory effect of leptin and
      mediates the sympathetic signal to the brown adipose tissue (BAT). In this
      context, physical exercise is one of the main interventions for the treatment of
      obesity. Thus, this study aimed to verify the effects of acute physical exercise
      on leptin-induced hypothalamic ERK1/2 phosphorylation and thermogenesis in obese
      mice. Here we showed that acute physical exercise reduced the fasting glucose of
      obese mice and increased leptin-induced hypothalamic p-ERK1/2 and uncoupling
      protein 1 (UCP1) content in BAT ( P < 0.05). These molecular changes are
      accompanied by an increased oxygen uptake (VO 2 ) and heat production in obese
      exercised mice ( P < 0.05). The increased energy expenditure in the obese
      exercised animals occurred independently of changes in spontaneous activity.
      Thus, this is the first study demonstrating that acute physical exercise can
      increase leptin-induced hypothalamic ERK1/2 phosphorylation and energy
      expenditure of obese mice.

PMID- 30206972
TI  - Comparison of large-scale deletions of the sperm mitochondrial DNA in
      normozoospermic and asthenoteratozoospermic men.
AB  - BACKGROUND AND OBJECTIVE: Mitochondria play a crucial role in energy metabolism
      for the survival and motility of sperm during fertilization. The aim of this
      study was to determine the association of large-scale mitochondrial DNA deletions
      with abnormal sperm motility and morphology in asthenoteratozoospermic patients.
      MATERIALS AND METHODS: In this case-control study, 41 semen samples were
      collected from 18 normozoospermic healthy men and 23 asthenoteratozoospermic
      patients, according to the WHO guidelines. The swim-up technique was used for
      separation of spermatozoa on the basis of their motility. Long-range polymerase
      chain reaction (PCR) was used for screening of mitochondrial DNA (mtDNA) large
      scale deletions, and primer shift PCR was used for confirmation of deletions.
      RESULTS: The mean sperm motility, normal morphology, and progressive motility in
      asthenoteratozoospermic patients were significantly lower than in the
      normozoospermic group (P < 0.0001). There was a positive significant correlation
      between motility and normal sperm morphology ( P < 0.0001, r = 0.741). The
      results of long-range PCR revealed the existence of 4866-bp deletion along with
      the two common 4977-bp and 7436-bp deleted mtDNA in both groups. However, the
      frequency of multiple mtDNA deletions in the asthenoteratozoospermic group
      (15/23, 65.22%) was significantly higher than that in the normozoospermic group
      (7/18, 38.89%). Direct sequencing of the 534-bp PCR product revealed that it was
      amplified from the mtDNA with a 4866-bp deletion flanked by a seven-nucleotide
      direct repeat (5'-ACCCCCT-3'). CONCLUSIONS: Our findings suggested that these
      large-scale deletions of mtDNA may be genetic risk factors for poor sperm quality
      in asthenoteratozoospermia-induced male infertility. Thus, it is necessary to
      understand the mechanisms behind the generation of these deletions.

PMID- 30206971
TI  - Liver kinase B1 overexpression controls mycobacterial infection in macrophages
      via FOXO1/Wnt5a signaling.
AB  - Mycobacterium tuberculosis (Mtb) is a primary cause of tuberculosis (TB), which
      has infected more than one-third of the world's population. Mtb survival and
      subsequent inflammation in macrophages are important components of TB. Liver
      kinase B1 (LKB1) has demonstrated anti-inflammation effects, but its function and
      underlying mechanism in mycobacteria-infected macrophages remains unknown. In the
      current study, we discovered that LKB1 was markedly decreased in Mtb-infected THP
      1 and U937 macrophages. Moreover, LKB1 overexpression inhibited Mtb survival in
      macrophages. Mtb infection increased expression of nitric oxide, inducible nitric
      oxide synthase, and inflammation-related cytokines interleukin (IL)-6, tumor
      necrosis factor-alpha, and IL-1beta, whereas pcDNA3-LKB1 transfection inhibited
      the release of these cytokines in THP-1 and U937 cells. Furthermore, LKB1
      overexpression significantly decreased protein expression of Wnt5a, which is
      dependent on the elevation of forkhead box protein O1 (FOXO1). Generally, we show
      that interruption of FOXO1 or overexpression of Wnt5a can reverse the effects of
      LKB1 on mycobacterial intracellular survival, nitric oxide, inducible nitric
      oxide synthase expression, and inflammatory cytokine release. These findings
      indicate important roles for LKB1, FOXO1, and Wnt5a in controlling mycobacteria
      and cell inflammation.

PMID- 30206973
TI  - Bisphenol A stimulates steroidogenic acute regulatory protein expression via an
      unknown mechanism in adrenal cortical cells.
AB  - Bisphenol A (BPA) is one of the most widespread endocrine disrupting chemicals in
      the environment. Exposure to BPA is known to be associated with disruption of
      steroidogenesis in reproductive tissues, but little is known about its effects on
      the adrenal gland. We previously showed that prenatal BPA exposure resulted in
      elevated plasma corticosterone levels concomitant with increased adrenal levels
      of steroidogenic acute regulatory protein (StAR), the rate-limiting step in
      steroidogenesis, in adult female mouse offspring. However, the molecular
      mechanisms underlying the BPA-induced StAR protein expression in the adrenal
      gland remain unknown. Therefore, the current study was designed to address this
      important question using the human cortical cell line, H295A cells, as an in
      vitro model system. We found that: (1) BPA increased StAR protein levels in a
      dose-dependent manner; (2) both estrogen receptor alpha (ERalpha)- and ERbeta
      specific agonists mimicked while the ER antagonist ICI abrogated the stimulatory
      effects of BPA on StAR protein levels; and (3) BPA did not alter StAR messenger
      RNA, 37kDa preprotein or protein half-life. Taken together, these findings
      demonstrate that BPA increases StAR protein levels through an unknown mechanism
      independent of StAR gene transcription, translation, and protein half-life.
      Furthermore, such effects are likely mediated by ERalpha and/or ERbeta.

PMID- 30206974
TI  - miR-214-5p targets KLF5 and suppresses proliferation of human hepatocellular
      carcinoma cells.
AB  - MicroRNAs (miRNAs) are small endogenous conserved RNAs regulating genes
      expression through base pairing with the 3'-untranslated region (3'-UTR) of
      target messenger RNAs. MiR-214-5p is a newly identified miRNA with its biological
      role largely unknown. In this study, we explored miR-214-5p expression status in
      78 paired tumor and nontumor tissues obtained from patients with hepatocellular
      carcinoma (HCC) by RT-qPCR. The effects of miR-214-5p expression on HCC cell
      proliferation, cell cycle progression, and cell migration were measured by CCK-8
      assay, flow cytometry, and wound-healing assay. A dual-luciferase activity assay
      was performed to identify whether KLF5 was a target of miR-214-5p. Kaplan-Meier
      curve and log-rank test were used to investigate the effects of miR-214-5p and
      KLF5 on overall survival and disease-free survival of patients with HCC. We found
      miR-214-5p expression was sharply reduced in HCC tissues and cell lines compared
      with the normal tissues and cell lines. Functional assay revealed that miR-214-5p
      overexpression could downregulate cell proliferation, cell migration, and
      arrested cell cycle at G0/G1 phase. Further, we validated Kruppel-like factor 5
      (KLF5) as a direct target of miR-214-5p, and was upregulated in HCC and inversely
      correlated with the expression of miR-214-5p. Moreover, we found the low
      expression of miR-214-5p and high expression of KLF5 were correlated with tumor
      size, tumor stage, and poorer 5-year overall survival and disease-free survival
      of patients with HCC. In conclusion, our results suggested miR-214-5p functions
      as a tumor suppressor through targeting KLF5 in HCC. Also, miR-214-5p and KLF5
      were identified as potential prognostic markers and might be therapeutic targets
      in HCC.

PMID- 30206976
TI  - Editorial: Symposium-in-Print on the Occasion of XIII ELAFOT (XIII Encuentro
      Latinoamericano de Fotoquimica y Fotobiologia).

PMID- 30206975
TI  - New N-benzhydrylpiperazine/1,3,4-oxadiazoles conjugates inhibit the
      proliferation, migration, and induce apoptosis in HeLa cancer cells via oxidative
      stress-mediated mitochondrial pathway.
AB  - N-benzhydrylpiperazine and 1,3,4-oxadiazoles are pharmacologically active
      scaffolds which exhibits significant inhibitory growth effects against various
      cancer cells, however, antiproliferation effects and the underlying mechanism for
      inducing apoptosis for aforementioned scaffolds addressing HeLa cancer cells
      remains uncertain. In this study, N-benzhydrylpiperazine clubbed with 1,3,4
      oxadiazoles (4a-4h) were synthesized, subsequently characterized using high
      resolution spectroscopic techniques and eventually evaluated for their
      antiproliferation potential by inducing apoptosis in HeLa cancer cells. The MTT
      assay screening results revealed that among all, compound 4d ( N-benzhydryl-4-((5
      (4-aminophenyl)-1,3,4-oxadiazol-2-yl)methyl)piperazine) in particular, exhibited
      IC 50 value of 28.13 +/- 0.21 MUg/mL and significantly inhibited the
      proliferation of HeLa cancer cells in concentration-dependent manner. The in
      vitro anticancer assays for treated HeLa cells resulted in alterations in the
      cell morphology, reduction in colony formation, and inhibition of cell migration
      in concentration-dependent treatment. Furthermore, G2/M phase arrest, variations
      in the nuclear morphology, degradation of chromosomal DNA confirmed the ongoing
      apoptosis in treated HeLa cells. Increase in the expression of cytochrome C and
      caspase-3 confirmed the involvement of intrinsic mitochondrial pathway regulating
      the cell death. Also, elevation in reactive oxygen species level and loss of
      mitochondrial membrane potential signified that compound 4d induced apoptosis in
      HeLa cells by generating the oxidative stress. Therefore, compound 4d may act as
      a potent chemotherapeutic agent against human cervical cancer.

PMID- 30206977
TI  - A unified mitochondria mechanistic target of rapamycin acyl-coenzyme A
      dehydrogenase 10 signal relay modulation for metformin growth inhibition in human
      immortalized keratinocytes cells.
AB  - Metformin exhibits antiproliferative and proapoptotic effects in a variety of
      diseases, characterized by malignant and nonmalignant hyperplastic cells;
      however, the underlying molecular mechanism of metformin in psoriasis has not
      been elucidated. In the current study, we found that after metformin treatment
      the proliferation of human immortalized keratinocytes (HaCaT) was significantly
      inhibited, while cell apoptosis was increased in a dose-dependent manner,
      accompanied with enhanced protein expression of acyl-coenzyme A dehydrogenase 10
      (ACAD10). Furthermore, mechanism analysis revealed that ACAD10 expression is
      induced by downregulated activities of mechanistic target of rapamycin 1 (mTORC1)
      signaling rather than AMP-activated protein kinase signaling. The inactivation of
      mTORC1 by rapamycin pretreatment or rotenone-induced mitochondrial complex
      inhibition showed a similar effect because of the metformin treatment on the
      proliferation and apoptosis of HaCaT keratinocytes. Overexpression of mTORC1
      almost reversed the antiproliferation and proapoptosis effects induced by
      metformin. This study showed that the metformin treatment inhibited HaCaT cells
      proliferation and promoted apoptosis by affecting the mitochondrial-mTORC1
      signaling and elevated the ACAD10 expression. Hence, metformin can be used as a
      potential therapeutic agent for psoriasis.

PMID- 30206978
TI  - Inhibition of miR146b-5p suppresses CT-guided renal cell carcinoma by targeting
      TRAF6.
AB  - Renal cell carcinoma (RCC) is one of the most common malignancies in the urinary
      system. Due to the lack of early symptoms, diagnosis of RCC usually occurs at
      late stages or after cancer metastasis leading to poor prognosis. Therefore, it
      is crucial to study early molecular mechanisms and biomarkers. Previous studies
      have suggested that microRNAs are involved in RCC initiation and development,
      making them a good candidate for early diagnosis and therapy. MiR146b-5P plays
      important roles in the progression of multiple cancers including thyroid cancer,
      pancreatic cancer, cervical cancer. However, it is not clear whether and how
      miR146b-5P is involved in RCC. In this study, we aimed to investigate the
      function of miR146b-5P in RCC. We examined the expression levels of miR146b-5p in
      renal cancer tissue and cell lines. We also explored the effects of blocking
      miR146b-5p in renal tumor growth and inflammatory signaling. Finally, we
      determined if miR146b-5p regulates tumorigenesis through TRAF6. We found that
      miR146b-5p levels were significantly increased in renal cancer tissue and renal
      cancer cells. Blocking miR146b-5p suppressed renal tumor growth and enhanced
      inflammatory response through increased TRAF6 expression. These effects were
      eliminated in TRAF6 knockout mice. Our results suggest that enhanced miR146b-5p
      expression may be a biomarker for RCC and modulating miR146b-5p and TRAF6 levels
      represent a potential therapeutic strategy for RCC.

PMID- 30206979
TI  - GPR177 promotes gastric cancer proliferation by suppressing endoplasmic reticulum
      stress-induced cell death.
AB  - Gastric cancer is the fourth most common cancer worldwide. Despite the high
      incidence of gastric cancer, efficient chemotherapy treatments still need to be
      developed. In this study, we examined the anticancer effects of endoplasmic
      reticulum (ER) stress inducer tunicamycin in gastric cancer. Previously, we found
      that overexpression of WLS1/GPR177 correlated with poor prognosis in patients
      with gastric cancer. Furthermore, tunicamycin treatment downregulated GPR177
      expression in a dose-dependent manner. GPR177 transports WNT ligand from ER to
      the plasma membrane, mediating its secretion to the extracellular matrix. In
      gastric cancer cells, GPR177 preferentially localizes to the ER. Small
      interfering RNA-mediated knockdown of GPR177 leads to sensitization to ER stress
      and induces apoptosis of cancer cells along with tunicamycin treatment. GPR177
      suppression promoted the ER stress-mediated proapoptotic pathway, such as PERK
      CHOP cascade. Furthermore, fluorouracil treatment combined with tunicamycin
      dramatically reduced cancer cell proliferation. Efficacy of tunicamycin
      chemotherapy treatments depended on GPR177 expression in gastric cancer cell
      lines. Together, our results indicate that ER stress can potentiate anticancer
      effects and suggest GPR177 as a potential gastric cancer therapeutic target.

PMID- 30206980
TI  - Silencing of microRNA-375 affects immune function in mice with liver failure by
      upregulating astrocyte elevated gene-1 through reducing apoptosis of Kupffer
      cells.
AB  - This study aims to investigate how microRNA-375 (miR-375) improves immune
      function by regulating liver macrophages (Kupffer cells) in mice with liver
      failure. Forty mice were divided into ConA-1h, ConA-3h, ConA-6h, and control
      groups, with 10 mice in each group. Mice models of liver failure were established
      by injecting concanavalin A (ConA) solution via the tail veins of mice, and then
      primary Kupffer cells were isolated and cultured. Reverse transcription
      quantitative polymerase chain reaction, Western blot analysis, and enzyme-linked
      immunosorbent assay were conducted to examine the expressions of miR-375,
      astrocyte elevated gene-1 (AEG-1), interleukin-6 (IL-6), tumor necrosis factor
      alpha (TNF-alpha), and IL-1beta in Kupffer cells of mice with liver failure as
      well as after silencing of miR-375. Flow cytometry was used to determine cell
      apoptosis. During the liver failure process, miR-375, IL-6, TNF-alpha, and IL
      1beta expressions were increased over time, while AEG-1 expression decreased over
      time in the control, ConA-1h, ConA-3h, and ConA-6h groups. Opposite alternations
      were observed after silencing of miR-375. Dual-luciferase reporter gene assay
      showed that AEG-1 was a target gene of miR-375. Flow cytometry determination
      showed that the ratio of apoptotic Kupffer cells decreased after silencing of miR
      375. Overexpression of AEG-1 could rescue the suppression of IL-6, TNF-alpha, and
      IL-1beta expressions in Kupffer cells after the short-term induction of ConA and
      further inhibit cell apoptosis. Our study provides evidence that miR-375 could
      regulate Kupffer cells to improve immune function in mice with liver failure.

PMID- 30206981
TI  - A novel seven-lncRNA signature for prognosis prediction in hepatocellular
      carcinoma.
AB  - Liver cancer is still one of the leading causes of cancer-related death
      worldwide. This study is dedicated to developing a multi-long noncoding RNA
      (lncRNA) model for risk stratification and prognosis prediction on patients with
      hepatocellular carcinoma (HCC). We first downloaded lncRNA expression profiles
      and corresponding clinical information of patients with liver cancer from The
      Cancer Genome Atlas database. Differentially expressed (DE) lncRNAs between HCC
      samples and normal samples were identified. In total, 308 patients with HCC were
      randomly divided into a training group (n = 154) and a testing group (n = 154).
      Univariate Cox regression and least absolute shrinkage and selection operator Cox
      regression analyses were performed to select the best survival-related candidates
      from these DE lncRNAs in the training set. Seven lncRNAs (AC009005.2, RP11
      363N22.3, RP11-932O9.10, RP11-572O6.1, RP11-190C22.8, RP11-388C12.8, and ZFPM2
      AS1) were finally identified and used to construct a seven-lncRNA signature. The
      signature could classify patients into high-risk and low-risk groups with
      significantly different overall survival. The area under the curve of receiver
      operating characteristic curve for the signature to predict 5-year survival
      reached more than 0.75. Besides, the prognostic value of the seven-lncRNA
      signature was independent of conventional clinical factors. The predictive
      performance of the signature was further validated in the testing set and the
      whole set. Functional enrichment analysis indicated that the seven prognostic
      lncRNAs may be involved in several essential biological processes and pathways.
      The current study demonstrated the potential clinical implications of the seven
      lncRNA signature for survival prediction of patients with HCC.

PMID- 30206982
TI  - Androgen receptor expression reduces stemness characteristics of prostate cancer
      cells (PC3) by repression of CD44 and SOX2.
AB  - Studies have shown that a subgroup of tumor cells possess stemness
      characteristics having self-renewal capacity and the ability to form new tumors.
      We sought to identify the plausible stemness factor that determines the
      "molecular signature" of prostate cancer (PCa) cells derived from different
      metastases (PC3, PCa2b, LNCaP, and DU145) and whether androgen receptor (AR)
      influences the maintenance of stemness features. Here we show sex-determining
      region Y (SRY)-box 2 (SOX2) as a putative stem cell marker in PC3 PCa cells and
      not in DU145, PCa2b, or LNCaP cells. PCa2b and PC3 cells were derived from bone
      metastases. PCa2b cells which are positive for the AR failed to demonstrate the
      expression of either cluster of differentiation 44 (CD44) or SOX2. Knockdown (KD)
      of AR in these cells did not affect the expression of either CD44 or SOX2.
      Conversely, PC3 cells, which are negative for AR, expressed both CD44 and SOX2.
      However, the expression of AR downregulated the expression of both CD44 and SOX2
      in PC3 cells. CD44 regulates SOX2 expression as KD of CD44 and reduces SOX2
      levels considerably. SOX2 KD attenuated not only the expression of SNAIL and SLUG
      but also the migration and tumorsphere formation in PC3 cells. Collectively, our
      findings underscore a novel role of CD44 signaling in the maintenance of stemness
      and progression of cancer through SOX2 in AR-independent PC3 cells. SOX2 has a
      role in the regulation of expression of SNAIL and SLUG. SOX2 could be a potential
      therapeutic target to thwart the progression of SOX2-positive cancer cells or
      recurrence of androgen-independent PCa.

PMID- 30206983
TI  - In silico analysis and molecular dynamics simulation of human superoxide
      dismutase 3 (SOD3) genetic variants.
AB  - Oxidative stress is a major factor in aging processes. Superoxide dismutase 3
      (SOD3) plays a key role in the protection of extracellular oxidative stress.
      Missense mutations in SOD3 have been described to be associated with the
      occurrence of pulmonary, cardiovascular, and neoplastic diseases. This study aims
      to analyze the effects of missense mutations on the SOD3 structure and function
      by modeling a complete SOD3 structure as well as analyzing the differences
      between the wild-types and mutants using computational simulations. Here, ten
      algorithms were used to predict the structural and functional effects of missense
      mutations. A complete model of SOD3 protein was made by ab initio and comparative
      modeling using the Rosetta algorithm and validated by PROCHECK, Verify 3D, QMEAN,
      and ProSa. Molecular dynamics (MD) simulations were performed and analyzed using
      the GROMACS package. The deleterious potential of the A58T and R231G mutants was
      not predicted by the majority of the used algorithms. The analyzed mutations were
      predicted as destabilizing by at least one algorithm. The MD analyses indicated
      that protein flexibility may be increased by all of the analyzed mutations, while
      the protein-ligand stability may be decreased. They also suggested that the
      variants A91T and R231G increase the overall dimensions of SOD3 and decrease its
      accessible surface area. Our findings, therefore, indicated that the analyzed
      mutations could affect the protein structure and its ability to interact with
      other molecules, which may be related to the functional impairment of SOD3 upon
      A58T and R231G mutations, as well as their involvement in pathologies.

PMID- 30206984
TI  - Increasing maternal age of blastocyst affects on efficient derivation and
      behavior of mouse embryonic stem cells.
AB  - Mouse embryonic stem cells (mESCs) have the capability to undergo unlimited cell
      division and differentiate into derivatives of all three embryonic germ layers.
      These fundamental features enable mESCs to potentially be appropriate, efficient
      models for biological and medical research. Therefore, it is essential to produce
      high-performance mESCs. In the current study, we have produced mESCs from
      blastocysts that developed from fertilized oocytes of 2 (2-C57)-, 4 (4-C57)-, and
      6 (6-C57)-month-old C57BL/6 mice. A comparison of isolated stem cells was done
      from the viewpoint of the efficiency of mESC derivation, self-renewal, and their
      differentiation capacity. All generated mESCs showed a similar expression of the
      molecular markers protein of pluripotency and AP activity. In the 3i medium,
      there was a significant decrease in undifferentiated marker genes expression in
      the 2-C57 cells compared with the other two groups ( P < 0.05) but developmental
      genes significantly increased in the 4-C57 and 6-C57 cells compared with the 2
      C57 cells ( P < 0.05). The differentiation capacity into three germ layers
      through the embryoid body formation and percentage of cell lines with normal
      numbers of chromosomes reduced with increased maternal age. The highest DT and
      highest percentage of cells in the S phase belonged to 2-C57 cells. These data
      demonstrated that blastocysts which developed from fertilized oocytes of 2-, 4-,
      and 6-month-old C57BL/6 mice can generate pluripotent stem cells, and suggested
      that both the efficiency of mESC isolation and the behavior of these isolated
      mESCs including pluripotency, self-renewal, cell cycle, and DT changed with
      increasing maternal age.

PMID- 30206985
TI  - Structural and energetic understanding of novel natural inhibitors of
      Mycobacterium tuberculosis malate synthase.
AB  - Persistent infection by Mycobacterium tuberculosis requires the glyoxylate shunt.
      This is a bypass to the tricarboxylic acid cycle in which isocitrate lyase (ICL)
      and malate synthase (MS) catalyze the net incorporation of carbon during
      mycobacterial growth on acetate or fatty acids as the primary carbon source. To
      identify a potential antitubercular compound, we performed a structure-based
      screening of natural compounds from the ZINC database (n = 1 67 740) against the
      M tuberculosis MS (MtbMS) structure. The ligands were screened against MtbMS, and
      354 ligands were found to have better docking score. These compounds were
      assessed for Lipinski and absorption, distribution, metabolism, excretion, and
      toxicity prediction where 15 compounds were found to fit well for redocking
      studies. After refinement by molecular docking and drug-likeness analysis, four
      potential inhibitors (ZINC1483899, ZINC1754310, ZINC2269664, and ZINC15729522)
      were identified. These four ligands with phenyl-diketo acid were further
      subjected to molecular dynamics simulation to compare the dynamics and stability
      of the protein structure after ligand binding. The binding energy analysis was
      calculated to determine the intermolecular interactions. Our results suggested
      that the four compounds had a binding free energy of -201.96, -242.02, -187.03,
      and -169.02 kJ.mol-1 , for compounds with IDs ZINC1483899, ZINC1754310,
      ZINC2269664, and ZINC15729522, respectively. We concluded that two compounds
      (ZINC1483899 and ZINC1754310) displayed considerable structural and
      pharmacological properties and could be probable drug candidates to fight against
      M tuberculosis parasites.

PMID- 30206986
TI  - Assessing the long-term effect of exposure to dispersant-treated oil on fish
      health using hypoxia tolerance and temperature susceptibility as ecologically
      relevant biomarkers.
AB  - The ecological and economic importance of fish act as a brake on the development
      of chemical dispersants as operational instruments following oil spills. Although
      a valuable and consistent body of knowledge exists, its use in spill response is
      limited. The objective of the present study was to increase current knowledge
      base to facilitate the translation of published data into information of
      operational value. Thus we investigated the dose-response relationship between
      dispersant-treated oil exposure and ecologically relevant consequences by
      combining laboratory and field experiments. Effects were examined over almost a
      year using juveniles of the slowly growing, commercially important European sea
      bass (Dicentrarchus labrax). A reliable interpretation of biomarker responses
      requires a complete knowledge of the factors likely to affect them.
      Interpopulational variability is of particular importance in environmental impact
      assessment because biomarker responses from a population collected in an impacted
      area are classically compared with those collected in a clean site. Our study
      revealed no effect of the exposure to dispersant-treated oil on fish hypoxia
      tolerance and temperature susceptibility at 1 and 11 mo post exposure. Similarly,
      no effect of the exposure was observed on the ability of the fish to cope with
      environmental contingencies in the field, regardless of the dose tested. Thus we
      feel confident to suggest that a 48-h exposure to chemically treated oil does not
      affect the ability of sea bass to cope with mild environmental contingencies.
      Finally, investigation of interpopulation variability revealed large differences
      in both hypoxia tolerance and temperature susceptibility among the 2 populations
      tested, suggesting that this variability may blur the interpretation of
      population comparisons as classically practiced in impact assessment. Environ
      Toxicol Chem 2018;9999:1-12. (c) 2018 SETAC.

PMID- 30206987
TI  - Bicuspid aortic valve repair with "self-made" radio-opaque rigid annuloplasty
      ring implantation.

PMID- 30206989
TI  - Use of Lean techniques in health care in Spain to improve involvement and
      satisfaction of workers.
AB  - The purpose of this study was to improve the organization of work, reduce
      physical effort, and obtain greater satisfaction of workers in the Pre-analytical
      Area of the Clinical Biochemistry Service at the Miguel Servet University
      Hospital of Zaragoza, in Spain, by applying Lean techniques. Such techniques were
      applied in two steps to obtain a final situation where the reduction of the space
      occupied, the required physical effort, and the work time is clear. The
      satisfaction of the workers was analyzed during the whole process by means of
      surveys, concluding that the sum of all the improvements managed to increase the
      satisfaction of the professionals. One key aspect to get these results was to use
      always the information and opinions of the staff making them feel the
      protagonists of the process. For that, it was essential the role of the agent of
      change that fundamentally sought the involvement of professionals in the
      improvement processes. Another key point was the careful application of Lean
      techniques always little by little, by applying small changes that became habits
      and achieved permanent results. In conclusion, in this work, a methodology to
      improve involvement and satisfaction of workers in health care has been presented
      and validated.

PMID- 30206988
TI  - Cognitive functioning transitions, health expectancies, and inequalities among
      elderly people in China: A nationwide longitudinal study.
AB  - OBJECTIVE: In China, cognitive impairment has become a huge challenge owing to
      the rapid aging process. We investigate cognitive health expectancy and potential
      factors leading to inequalities of cognitive health for Chinese older people.
      METHODS: The study included 19 943 participants aged 65 to 95 at the first
      observation in Chinese Longitudinal Healthy Longevity Survey collected during
      2002-2014. Cognitive impairment was categorized into none, mild, and severe by
      the score of cMMSE. Multistate models based on continuous-time Markov process
      were applied to calculate cognitive health expectancies and estimate hazard ratio
      from no impairment to impairment for potential factors. RESULTS: Urban women and
      men aged 65 were expected to spend 31.18% and 19.82% of their remaining 17.46 and
      15.45 years with cognitive impairment; meanwhile, rural women and men aged 65
      were expected to spend 35.31% and 21.39% of their remaining 16.73 and 14.87 years
      with cognitive impairment. Women achieving lower educational attainment (HR1-6
      years  = 0.78, 95% CI, 0.71-0.87; HR7+ years  = 0.59, 95% CI, 0.49-0.70) than men
      and rural residents having less access to medical service (HR = 0.79, 95% CI,
      0.68-0.92) and doing less regular exercise (HR = 0.87, 95% CI, 0.80-0.96) than
      urban people caused the differences of cognitive health for genders and regions.
      CONCLUSIONS: Women and rural people experience less cognitive health expectancies
      compared with their counterparts, respectively. Chinese government should pay
      more attention to rural women and make efforts to reduce the inequalities of
      cognitive health by increasing opportunities of education for women and improving
      access to medical service and healthy lifestyle for rural people.

PMID- 30206990
TI  - Detrimental effects of incomplete revascularization following CABG-multiple
      arterial grafting may not solve the problem.

PMID- 30206991
TI  - Detection of microscopic diffusion anisotropy in human cortical gray matter in
      vivo with double diffusion encoding.
AB  - PURPOSE: To detect microscopic diffusion anisotropy in human cortical gray matter
      in vivo with double diffusion encoding experiments. METHODS: Double diffusion
      encoding experiments were performed on a 3 T whole-body MR system using echo
      planar imaging. Angular double diffusion encoding measurements were acquired with
      8 * 8 and 12 * 12 planar direction combinations and were analyzed in three
      regions of interest containing white matter, mostly cortical gray matter, and one
      having significant contributions from cerebrospinal fluid. Inversion with
      variable recovery times served to estimate and eliminate white matter partial
      volume effects. To investigate the influence of magnetic field inhomogeneities,
      experiments with gradient offsets and cross-term compensated diffusion weightings
      were performed. The MA index, a rotationally invariant measure of the microscopic
      diffusion anisotropy, was determined from measurements with 96 direction
      combinations. RESULTS: The angular signal modulation in the gray matter region of
      interest has two components, one being consistent, inter alia, with cross terms
      with field inhomogeneities while the other represents a signal difference between
      parallel/antiparallel and orthogonal direction combinations, ie, the fingerprint
      of microscopic diffusion anisotropy. Based on the amplitudes and their dependency
      on the inversion time, white matter partial volumes can be excluded as the sole
      source for this modulation, providing strong evidence for the detection of
      microscopic diffusion anisotropy in cortical gray matter. MA maps of healthy
      volunteers show considerably lower values in cortical gray matter compared with
      white matter. CONCLUSION: Microscopic diffusion anisotropy can be measured in
      human cortical brain matter, which could help to characterize the microstructure
      of healthy and pathological tissue.

PMID- 30206992
TI  - Coexpression network analysis identified Kruppel-like factor 6 (KLF6) association
      with chemosensitivity in ovarian cancer.
AB  - Although most patients with ovarian cancer (OC) are initially sensitive to
      paclitaxel/carboplatin combination chemotherapy, eventually they develop
      resistance to chemotherapy drugs and experience disease relapse. OC is the most
      lethal gynecological malignancy, and the five-year survival rate is extremely
      low. Thus, research on specific biomarkers and potential targets for chemotherapy
      resistant patients with OC is needed. In our study, genes in the top 10% of
      variance in data set GSE30161 from chemoresistant and chemosensitive OC tissues
      were determined to conduct a weighted gene coexpression network analysis (WGCNA).
      The magenta module was most strongly related to OC chemoresponse. Gene ontology
      enrichment analysis indicated that the function of the magenta module primarily
      focused on transcription regulation, cell cycle control, and apoptosis
      modulation. Integration of the WGCN with the protein-protein interaction network
      identified five candidate genes. These five genes were verified using the
      GSE51373 test set, and Kruppel-like factor 6 ( KLF6) was identified as tightly
      linked to OC chemosensitivity. The receiver operating characteristic (ROC) curve
      showed that KLF6 differentiated chemoresistant from chemosensitive OC tissues.
      The Kaplan-Meier online database indicated that high KLF6 expression was
      associated with poor OC prognosis. Gene set enrichment analysis determined that
      the KLF6 mechanism was potentially associated with cell cycle, mTOR, and DNA
      damage repair signaling pathways. In conclusion, KLF6 was identified in
      association with OC chemoresistance, and the mechanism of KLF6-mediated
      chemoresistance may involve the cell cycle, mTOR, and DNA-damage repair signaling
      pathways.

PMID- 30206993
TI  - Convergence insufficiency in Chinese high school students.
AB  - BACKGROUND: The frequency of convergence insufficiency was determined in a sample
      of Chinese high school students. The associations between the frequency of
      convergence insufficiency, gender, refractive error and accommodative
      insufficiency were investigated. METHODS: This was a single-site, prospective
      cross-sectional study. In total, 928 eligible teenagers (mean age 15.9 +/- 0.8)
      from a local high school in Guangzhou, Guangdong Province, China participated in
      this study. Refraction and binocular vision tests were performed on all eligible
      participants. The following three signs were used to classify participants: sign
      1, exophoria at near at least 4? greater than at far; sign 2, receded near point
      of convergence (>= 6 cm break point); and sign 3, insufficient near positive
      fusional vergence (that is, failing Sheard's criterion or <= 15? break point).
      Diagnostic groups of convergence insufficiency classification were defined as
      follows: (1) 3-Sign convergence insufficiency (all three signs present); (2) 2
      Sign convergence insufficiency (sign 1 plus sign 2 or 3); (3) 1-Sign convergence
      insufficiency (sign 1 only); and (4) no convergence insufficiency (that is,
      participants not classified into one of the above groups). RESULTS: The number
      and frequency of individuals with 3-Sign, 2-Sign, and 1-Sign convergence
      insufficiency as well as no convergence insufficiency group were 25 (2.7 per
      cent), 119 (12.8 per cent), 303 (32.6 per cent) and 481 (51.8 per cent),
      respectively. Gender (chi2  = 36.6, df = 3, p < 0.001), refractive error grouping
      (chi2  = 37.7, df = 9, p < 0.001) and accommodative insufficiency (chi2  = 15.4,
      df = 3, p = 0.002) were all significantly associated with convergence
      insufficiency. Male gender, hyperopia, or accommodative insufficiency were more
      likely to be classified with 3-Sign convergence insufficiency. The frequency of
      accommodative insufficiency was 9.5 per cent (88 of 928 participants).
      CONCLUSION: Compared to the data from school- and clinic-based populations in the
      USA and South Africa, the data from this sample of Chinese high school students
      showed a lower frequency of 3-Sign convergence insufficiency (2.7 per cent).
      Convergence insufficiency was associated with refractive error, gender and
      accommodative insufficiency.

PMID- 30206994
TI  - CEST MRI of 3-O-methyl-D-glucose uptake and accumulation in brain tumors.
AB  - PURPOSE: 3-O-Methyl-D-glucose (3-OMG) is a nonmetabolizable structural analog of
      glucose that offers potential to be used as a CEST-contrast agent for tumor
      detection. Here, we explore it for CEST-detection of malignant brain tumors and
      compare it with D-glucose. METHODS: Glioma xenografts of a U87-MG cell line were
      implanted in five mice. Dynamic 3-OMG weighted images were collected using CEST
      MRI at 11.7 T at a single offset of 1.2 ppm, showing the effect of accumulation
      of the contrast agent in the tumor, following an intravenous injection of 3-OMG
      (3 g/kg). RESULTS: Tumor regions showed higher enhancement as compared to
      contralateral brain. The CEST contrast enhancement in the tumor region ranged
      from 2.5-5.0%, while it was 1.5-3.5% in contralateral brain. Previous D-glucose
      studies of the same tumor model showed an enhancement of 1.5-3.0% and 0.5-1.5% in
      tumor and contralateral brain, respectively. The signal gradually stabilized to a
      value that persisted for the length of the scan. CONCLUSIONS: 3-OMG shows a CEST
      contrast enhancement that is approximately twice as much as that of D-glucose for
      a similar tumor line. In view of its suggested low toxicity and transport
      properties across the BBB, 3-OMG provides an option to be used as a nonmetallic
      contrast agent for evaluating brain tumors.

PMID- 30206995
TI  - d-transposition of great arteries, dextrocardia with aberrant origin of right
      subclavian artery from pulmonary artery.

PMID- 30206996
TI  - Energy Materials Design for Steering Charge Kinetics.
AB  - Charge kinetics is a critical factor that determines working efficiencies of
      energy materials in their various applications. It is governed by electronic
      structures of the materials of interest and can be fine-tuned via purposeful
      adjustment of electronic structures. Recent advances in the development of energy
      materials with desirable electronic structures to steering charge kinetics toward
      specific applications are highlighted here. Two key strategies are presented: one
      is through the tuning of energy states and the other is to control spatial
      distributions of charges. Each strategy is described by several different
      schemes. Finally, the challenges and perspectives in designing energy materials
      with fine control of charge kinetics are discussed.

PMID- 30206997
TI  - Aggression, attributional style, and locus of control among imprisoned migrants
      from the former Soviet Union.
AB  - BACKGROUND: In the 1990s, over two million migrants from the former Soviet Union
      with German ancestry came to Germany, a small number of whom committed offences.
      AIM: The aim of this study is to investigate aggression, locus of control, and
      attributional style in these (male) migrants imprisoned in Germany. METHODS:
      Three groups of men with German ancestry were compared: 1.36 prisoners migrating
      into Germany from the former Soviet Union (migrant-P), 2.31 migrating into
      Germany from the former Soviet Union without a history of offending (community
      sample; C), and 3.40 German prisoners with no migration experience (native-P).
      RESULTS: Aggression was high among all prisoners relative to nonoffending
      migrants. Prisoners tended to be under-achievers educationally compared with
      community living migrants. Imprisoned migrants had scores on locus of control and
      on attribution scales of feeling more influenced by fate and other external
      factors than had the community migrants, but in a regression model with
      aggression as the dependent variable and locus of control and attributional style
      measures as the independent variables, only external attributional style with
      respect to failure was significantly related to aggression. IMPLICATIONS:
      External attributional style appears to be linked to the probability of
      aggressive behaviours, leading to unlawful acts and imprisonment. Regardless of
      whether a person has a migration history or not, as attribution of failure among
      these relatively low-achieving prisoners was associated with aggression,
      loosening these attributional tendencies in therapy might help to reduce
      aggression. Migration per se was not problematic in these respects in this
      sample.

PMID- 30206998
TI  - From 1949 to 2018: R. A. Fisher's Theory of Junctions.

PMID- 30206999
TI  - R.A. Fisher and the development of statistics.

PMID- 30207000
TI  - The efficacy of oral Zhizhu Kuanzhong, a traditional Chinese medicine, in
      patients with postprandial distress syndrome.
AB  - BACKGROUND AND AIM: The treatment of patients with functional dyspepsia (FD)
      remains unsatisfactory. We assessed the efficacy of Zhizhu Kuanzhong (ZZKZ)
      capsule, a traditional Chinese medicine formula, in patients with postprandial
      distress syndrome (PDS) of FD. METHODS: The study was designed as a multicenter,
      randomized, double-blinded, controlled clinical trial. Three-hundred ninety-two
      patients with PDS defined by Rome III criteria from 16 centers in China were
      randomly assigned to receive either ZZKZ or placebo. The proportion of the
      responders at 4 weeks after randomization was considered primary endpoint.
      Secondary endpoint was the symptom score reduction of each dyspeptic symptom
      relative to the baseline at 4 weeks after randomization in all subjects. RESULTS:
      In terms of the primary endpoint, the proportion of the responders concerning the
      composite PDS symptom score was 38.8% and 54.7% in placebo group and ZZKZ group,
      respectively (P = 0.003), in per protocol analysis at 4 weeks after
      randomization. Concerning the individual evaluated upper gastrointestinal
      symptoms, only postprandial fullness and early satiety showed significant
      difference in symptom score reduction at 4 weeks after randomization between
      placebo and ZZKZ groups. CONCLUSIONS: Zhizhu Kuanzhong is superior to placebo in
      the treatment of PDS with FD. The exact mechanisms by which ZZKZ improves
      symptoms remain to be established (http://www.chictr.org.cn/ChinCTR-TRC
      14004714).

PMID- 30207001
TI  - Hindbrain morphometry and choroid plexus position in the differential diagnosis
      of posterior fossa cystic malformations.
AB  - OBJECTIVE: To assess the differential diagnostic significance of a series of
      quantitative and qualitative variables of the cerebellar vermis in 67 cases of
      posterior fossa cystic malformations including Dandy-Walker Malformation (DWM),
      Vermian Hypoplasia (VH), and Blake's Pouch Cyst (BPC), with particular attention
      at the differential diagnosis of the last two entities. METHODS: This is a
      retrospective study including all cases of DWM, VH and BPC diagnosed in the
      period 2005-2017, with good quality three-dimensional volume datasets of the
      posterior fossa acquired transvaginally, through the posterior fontanelle. The
      midisagittal view of the posterior fossa was the reference view for the study.
      The following variables were assessed: brainstem-tentorium angle (BTA), brainstem
      vermis angle (BVA), cranio-caudal and antero-posterior diameters and area of the
      vermis. The last 3 parameters were normalised by BPD, to take advancing
      gestational age into account (CCVD/BPD*100, APVD/BPD*100, VA/BPD*100). Finally,
      the position of the 4th ventricular choroid plexus (4VCP) was defined as normal
      ("UP") or abnormal ("DOWN"), in relation to its position in relation to the 4th
      ventricle roof/cyst inlet). RESULTS: Sixty-seven cases of posterior fossa
      malformations were analysed (DWM 24 cases, VH, 13 cases, BPC, 30 cases). Mean
      gestational age at acquisition was 23.6 completed weeks. All variables were
      significantly different in the three categories, but the best Area Under the
      Curve was shown by the VA/BPD ratio, both on the whole series and in cases < 23
      gestational weeks (p < 0.05 and p < 0.001, respectively). As for the 4VCP
      position, it was DOWN in all cases of DWM and VH, while it was UP in all cases of
      BPC. CONCLUSIONS: Our data seem to support the concept that, to differentiate
      between DWM, VH and BPC in the fetus, the VA/BPD ratio and the 4VCP position
      should be used. The latter has shown in our series the highest accuracy, but we
      feel that a larger number of VH cases should be evaluated to state without doubts
      that an UP position of the 4VCP identifies BPC while a DOWN position is
      univocally found in DWM or VH. This article is protected by copyright. All rights
      reserved.

PMID- 30207002
TI  - Multivariable evaluation of the maternal hemodynamic profile in pregnancies
      complicated by intrauterine growth restriction: a prospective study.
AB  - BACKGROUND: The aim of this study was to evaluate the effect of intrauterine
      growth restriction on maternal hemodynamic parameters using a multivariable
      analysis, adjusting for major confounding factors, such as hypertensive disorders
      of pregnancy (preeclampsia and gestational hypertension). METHODS: A prospective
      cohort study was conducted between January 2013 and April 2016. Two cohorts of
      patients were recruited, between 24 and 39 weeks of gestation in high risk
      outpatient setting. These cohorts were composed of 49 appropriate for gestational
      age fetuses and 93 intrauterine growth restricted fetuses (abdominal
      circumference at recruitment <= 10th percentile). Maternal echocardiography was
      performed at the time of enrollment and included hemodynamic parameters of
      systolic-diastolic function and cardiac remodeling indices. Data were analyzed
      using a multivariable general linear model. The general linear model coefficients
      were used to estimate the effect of intrauterine growth restriction after
      adjusting for significant confounding factors of hemodynamic parameters. RESULTS:
      In multivariable analysis, after adjustment for hypertension and smoking,
      intrauterine growth restriction resulted in a 10% about increase in total
      vascular resistance and a 10% about reduction in heart rate, cardiac output and
      left ventricular mass; the same results were confirmed also for indexed
      parameters. The effect of hypertensive disorders of pregnancy alone produced a
      30% about increase in total vascular resistance and 12% about increase in left
      ventricular mass and 13% reduction in diastolic function; the same results were
      confirmed also for indexed parameters. CONCLUSIONS: In pregnancies complicated by
      intrauterine growth restriction and hypertensive disorders, intrauterine growth
      restriction has a significant independent effect on most maternal hemodynamic
      parameters, even after adjustment for major cardiovascular confounding factors.
      This article is protected by copyright. All rights reserved.

PMID- 30207003
TI  - Cognitive behaviour therapy for distress in people with inflammatory bowel
      disease: A benchmarking study.
AB  - OBJECTIVE: Anxiety and depression are common in inflammatory bowel disease (IBD)
      and have been linked to clinical recurrence. Previous randomized controlled
      trials (RCT's) have found no evidence that psychological interventions enhance
      outcomes for people with IBD but have recruited patients without distress. This
      study investigates the clinical benefits of a nonrandomized uncontrolled study of
      clinic based cognitive behaviour therapy (CBT) for people with IBD who had
      moderate-severe levels of anxiety or low mood and compares the results with a
      previous RCT of CBT in this population. METHOD: Assessments were completed at
      baseline and end of treatment and included measures of low mood, generalized
      anxiety, quality of life (QOL), and symptomatic disease activity. The patient
      health questionnaire and generalized anxiety disorder 7 measures were the primary
      outcomes. Results in the form of a standardized effect size of treatment were
      compared with a previous RCT to consider if CBT had greater benefits for those
      with distress. RESULTS: Thirty patients were deemed appropriate for CBT, and 28
      accepted treatment. The results from this clinic based CBT intervention suggest
      statistically significant reductions in symptoms of anxiety (<0.001), low mood
      (<0.001), and disease activity (p < 0.01) and increases in QOL (p < 0.001). The
      uncontrolled effect sizes were large and superior to those found in published
      RCTs. CONCLUSION: This nonrandomized uncontrolled trial of a clinic-based CBT
      intervention suggests that CBT may have benefits for those with moderate-severe
      disturbances to mood and that effect sizes can be improved by targeting those
      with distress. RCTs are required to establish efficacy.

PMID- 30207005
TI  - Structure and role for active site lid of lactate monooxygenase from
      Mycobacterium smegmatis.
AB  - : Lactate monooxygenase (LMO) catalyzes the FMN-dependent "coupled" oxidation of
      lactate and O2 to acetate, carbon dioxide, and water, involving pyruvate and
      hydrogen peroxide as enzyme-bound intermediates. Other alpha-hydroxy acid oxidase
      family members follow an "uncoupled pathway," wherein the alpha-keto acid product
      quickly dissociates before the reduced flavin reacts with oxygen. Here, we report
      the structures of Mycobacterium smegmatis wild-type LMO and a wild-type-like
      C203A variant at 2.1 A and 1.7 A resolution, respectively. The overall LMO fold
      and active site organization, including a bound sulfate mimicking substrate,
      resemble those of other alpha-hydroxy acid oxidases. Based on structural
      similarity, LMO is similarly distant from lactate oxidase, glycolate oxidase,
      mandelate dehydrogenase, and flavocytochrome b2 and is the first representative
      enzyme of its type. Comparisons with other alpha-hydroxy acid oxidases reveal
      that LMO has a longer and more compact folded active site loop (Loop 4), which is
      known in related flavoenzymes to undergo order/disorder transitions to allow
      substrate/product binding and release. We propose that LMO's Loop 4 has an
      enhanced stability that is responsible for the slow product release requisite for
      the coupled pathway. We also note electrostatic features of the LMO active site
      that promote substrate binding. Whereas the physiological role of LMO remains
      unknown, we document what can currently be assessed of LMO's distribution in
      nature, including its unexpected occurrence, presumably through horizontal gene
      transfer, in halophilic archaea and in a limited group of fungi of the genus
      Beauveria. BROAD STATEMENT OF IMPACT: This first crystal structure of the FMN
      dependent alpha-hydroxy acid oxidase family member lactate monooxygenase (LMO)
      reveals it has a uniquely large active site lid that we hypothesize is stable
      enough to explain the slow dissociation of pyruvate that leads to its "coupled"
      oxidation of lactate and O2 to produce acetate, carbon dioxide, and water. Also,
      the relatively widespread distribution of putative LMOs supports their importance
      and provides new motivation for their further study.

PMID- 30207004
TI  - Examining contradictory evidence on racial/ethnic differences in perceived need
      for behavioral health treatment.
AB  - OBJECTIVES: The study aims to investigate apparently contradictory evidence
      regarding racial/ethnic differences in perceived need for behavioral health
      treatment in two prominent surveys of the U.S. population, the National
      Comorbidity Survey Replication (NCS-R) and the National Survey of Drug Use and
      Health (NSDUH). METHODS: The two surveys were compared with respect to two
      components of perceived need: service use and perceived need among the untreated.
      Logistic regression models were estimated to adjust comparisons for demographic
      characteristics. Comparisons were conducted in samples representing the entire
      population, without selection on a mental health assessment, and for samples
      meeting criteria for lifetime major depression. RESULTS: The surveys are
      concordant with respect to racial/ethnic differences in service use and
      discordant with respect to perceived need among the untreated. For instance,
      among untreated individuals, the odds of perceiving a need for treatment are
      significantly higher in Blacks than Whites in the NCS-R (OR = 1.8, 95% CI [1.1,
      2.9]) but do not differ between these groups in the NSDUH (OR = 0.9, 95% CI [0.7,
      1.2]). Temporal trends do not appear to explain this discordance. CONCLUSION:
      Assessments of racial/ethnic differences in perceived need among untreated
      individuals are affected by methodological differences across surveys. Resolving
      contradictory evidence is critical to efforts to reduce racial/ethnic
      disparities.

PMID- 30207007
TI  - Modulation of specific cell cycle phases in human embryonic stem cells by lncRNA
      RNA decoys.
AB  - Recent studies have shown that long noncoding RNAs (lncRNAs) are crucial
      regulators of human embryonic stem cells (hESCs). However, modes of actions of
      lncRNAs in hESCs are not well illustrated. Here, we predicted a regulatory
      network in hESCs in which lncRNAs interact with TFs and thereby control the
      expressions of downstream targets of TFs. The predicted network is comprised of
      2289 3-motif subgraphs which are characterized by 3 nodes: (i) a lncRNA which is
      predicted to interact with (ii) a TF and (iii) a gene which is a target of TF and
      coexpressing with lncRNA. We performed functional annotation of the network by
      identifying hub nodes followed by pathway enrichment study, which unveiled an
      active G1-S cell cycle phase transition-specific subnetwork that encompasses 2
      lncRNAs, MALAT1 and DANCR. Our analysis revealed that MALAT1 and DANCR might be
      playing key roles in G1-S phase transition by acting as RNA decoy via interacting
      with crucial stemness maintaining TFs. We predicted that MALAT1 possibly compete
      with DNMT1 and CDCA7 genes to bind to E2F1 thereby interrupting repression of
      DNMT1 and activation of CDCA7 by E2F1 in hESCs, whereas DANCR possibly competes
      with IPO7 gene to bind to MYC thereby interrupting MYC-mediated activation of
      IPO7 in hESCs. Both of these are conjectured to contribute to rapid G1-S phase
      transition aiding in stemness maintenance of hESCs. This study presents a crucial
      TF target cross talks mediated by lncRNAs in hESCs regulating its properties
      which needs further investigation.

PMID- 30207006
TI  - Task-enhanced arterial spin labeled perfusion MRI predicts longitudinal
      neurodegeneration in mild cognitive impairment.
AB  - Mild cognitive impairment (MCI) is considered a prodromal stage of Alzheimer's
      disease (AD), but is also recognized to be a heterogeneous condition. Biomarkers
      that predict AD progression in MCI are of clinical significance because they can
      be used to better identify appropriate candidates for therapeutic intervention
      studies. It has been hypothesized that comparing to structural measurements,
      functional ones may be more sensitive to early disease abnormalities and the
      sensitivity could be further enhanced when combined with cognitive task, a "brain
      stress test." In this study, we investigated the value of regional cerebral blood
      flow (CBF), measured by arterial spin labeled perfusion MRI (ASL MRI) during a
      memory-encoding task, in predicting the estimated rate of hippocampal atrophy, an
      established marker of AD progression. Thirty-one amnestic MCI patients (20 male
      and 11 female; age: 70.9 +/- 6.5 years, range from 56 to 83 years; mini mental
      status examination: 27.8 +/- 1.8) and 42 normal control subjects (13 male and 29
      female; age: 70.6 +/- 8.8 years, range from 55 to 88 years; mini mental status
      examination: 29.1 +/- 1.2) were included in this study. We compared the
      predictive value of CBF during task to CBF during rest and structural volumetry.
      Both region-of-interest and voxelwise analyses showed that baseline CBF
      measurements during task (strongest effect in fusiform gyrus, region-of-interest
      analysis statistics: r = 0.56, p = .003), but not resting ASL MRI or structural
      volumetry, were correlated with the estimated rate of hippocampal atrophy in
      amnestic MCI patients. Further, stepwise linear regression demonstrated that
      resting ASL MRI and volumetry did not provide complementary information in
      prediction. These results support the notion that physiologic measures during a
      cognitive challenge may increase the ability to detect subtle functional changes
      that predict progression. As such, ASL MRI could have important utility in
      stratifying candidates for AD treatment trials.

PMID- 30207009
TI  - Role of fetal inter-twin middle cerebral artery peak systolic velocity
      differences in predicting neonatal twin anemia-polycythemia sequence (TAPS).

PMID- 30207010
TI  - Double standards and gold standards in the evaluation of how a person feels and
      functions in substance use disorder pharmacotherapy trials.

PMID- 30207008
TI  - alpha-Fluoroalcohols: Synthesis and Characterization of Perfluorinated Methanol,
      Ethanol and n-Propanol, and their Oxonium Salts.
AB  - The thermally unstable, primary perfluoroalcohols, CF3 OH, C2 F5 OH, and nC3 F7
      OH, were conveniently prepared from the corresponding carbonyl compounds in
      anhydrous HF solution. Experimental values for the reaction enthalpies and
      entropies were derived from the temperature dependence of the Rf COF+HF?Rf CF2 OH
      (Rf =F, CF3 , CF3 CF2 ) equilibria by NMR spectroscopy. Electronic structure
      calculations of the gas-phase and solution reaction energies, gas-phase acidities
      and heats of formation were carried out at the G3MP2 level, showing that these
      compounds are strong acids. Protonation of these alcohols in HF/SbF5 produced the
      perfluoroalkyl oxonium salts Rf CF2 OH2 + SbF6 - .

PMID- 30207011
TI  - Perinatal outcome of monochorionic twin pregnancies complicated by selective
      fetal growth restriction according to management: a systematic review and meta
      analysis.
AB  - OBJECTIVES: To explore the impact of severity and management (expectant, laser
      treatment or selective reduction) on perinatal outcome of monochorionic twin
      pregnancies complicated by selective intra-uterine growth restriction (sFGR).
      METHODS: Medline, EMBASE, ClinicalTrials.gov and the Cochrane database were
      searched. Only pregnancies affected by sFGR and categorized according to the
      Gratacos classification (Type I, II and III) were included. The primary outcome
      was mortality, including single and double intrauterine (IUD), neonatal (NND) and
      perinatal death (PND). The secondary outcomes were neonatal morbidity, abnormal
      post-natal brain imaging, intra-ventricular hemorrhage (IVH), peri-ventricular
      leukomalacia (PVL), respiratory distress syndrome (RDS), admission to neonatal
      intensive care unit (NICU) and survival free from neurological complications
      (intact survival). Meta-analyses of proportions were used to analyze the
      extracted data. RESULTS: Fifteen observational studies (784 monochorionic twin
      pregnancies) were included. In pregnancies complicated by type I sFGR managed
      expectantly, IUD occurred in 3.1% (95% CI 1.1-5.9) and 97.9% (95% CI 93.6-99.9)
      had intact survival free from neurological complications. In Type I sFGR treated
      with laser therapy, IUD occurred in 16.7% (95% CI 0.4-64.1) and with cord
      occlusion, IUD occurred in 0% (95% CI 0-34.9) co-twins with no evidence of
      neurological complications in the survivors. In pregnancies complicated by type
      II sFGR managed expectantly, IUD occurred in 16.6% (95% CI 6.9-29.5), NND in 6.4%
      (95% CI 0.2-28.2), and 89.3% (95% CI 71.8-97.7) of twins survived without
      neurological compromise. With laser therapy, IUD occurred in 44.3% (95% CI 22.2
      67.7), while none of the affected cases experienced morbidity and survivors were
      free of neurological complications. In pregnancies undergoing selective
      reduction, IUD of the co-twin occurred in 5.0% (95% CI 0.03-20.5), NND in 3.7%
      (95% CI 0.2-11.1) and 90.6% (95% CI 42.3-94.3) of surviving co-twins were free
      from neurological complications. In pregnancies complicated by type III sFGR
      managed expectantly, IUD occurred in 13.2% (95% CI 7.2-20.5), NND in 6.8% (95% CI
      0.7-18.6) and 61.9% (95% CI 38.4-81.9) had intact survival, free from
      neurological complications. In pregnancies treated with laser therapy, IUD
      occurred in 32.9% (95% CI 20.9-46.2) and all twins treated with laser survived
      without neurological complications. Finally, in pregnancies treated with cord
      occlusion NND occurred in 5.2% (95% CI 0.8-12.8) of co-twins and 98.8% (95% CI
      93.9-99.9) had intact survival. CONCLUSION: Type I sFGR is characterized by good
      perinatal outcome with expectant management, which represents the most reasonable
      management strategy for the large majority of affected cases. Pregnancies
      complicated by Type II and III sFGR treated with fetoscopic laser ablation had
      higher mortality but lower morbidity compared to those managed expectantly,
      supporting the use of fetal therapy at gestations remote from neonatal viability 
      with scarce data on outcome following selective reduction. However, in view of
      the lack of evidence from randomized controlled trials, prenatal management of
      sFGR should be individualized according to gestational age at diagnosis, severity
      of growth discordance and magnitude of Doppler anomalies. This article is
      protected by copyright. All rights reserved.

PMID- 30207013
TI  - Ultrasound assessment of the prevalence of increased gastric contents and volume
      in elective pediatric patients: A prospective cohort study.
AB  - BACKGROUND: Though pulmonary aspiration of gastric contents occurs mainly in the
      setting of emergency surgery, it may also occur in children scheduled for
      elective surgery without any obvious clinical risk factor. Increased gastric
      content volume is one the predisposing factors for pulmonary aspiration that
      could affect such children and may be identified using ultrasound examination of
      the gastric antrum. AIMS: We aimed to assess the prevalence of "at-risk stomach"
      defined by ultrasound visualization of any solid content in the antrum and/or by
      calculated gastric fluid volume > 1.25 mL/kg, in children scheduled for elective
      surgery. METHODS: Children scheduled for elective surgery were consecutively
      included into this prospective cohort study. Preoperative ultrasound examination
      of the antrum was performed in both the supine and the right lateral decubitus
      positions. Gastric fluid content was assessed using a 0-2 qualitative grading
      scale. The antral cross-sectional area was also measured in both the supine and
      the right lateral decubitus positions, allowing the calculation of the gastric
      fluid volume according to a formula previously described. RESULTS: We analyzed
      200 elective children. Median duration of fasting was 4 hours for liquids and >13
      hours for solids. None of the children included in this study had evidence of
      solid content. Six (3%) children had a Grade 2 antrum (fluid content seen in both
      the supine and the right lateral decubitus positions). Two children had a gastric
      fluid volume >1.25 mL/kg. The prevalence of "at-risk stomach" was 1% (95%
      confidence interval: 0.2%-3.9%). CONCLUSION: According to our results, only 1% of
      elective children had potentially increased risk for pulmonary aspiration.
      Further studies should be performed in order to define the target population of
      elective children for which ultrasound assessment of gastric content should be
      performed prior to general anesthesia.

PMID- 30207012
TI  - Transgenerational transmission of small for gestational age.
AB  - OBJECTIVE: To evaluate the transgenerational transmission of small for
      gestational age. METHODS: Cohort study including a random sample of 2,043
      offspring of deliveries occurring from 1975 to 1993. Of 623 offspring -now adults
      that agreed to participate, 152 adults (72 born small-for-gestational age (SGA)
      and 80 with appropriate intrauterine growth) reported to have at least one child.
      Multiple regression analysis was used to determine the presence of SGA (defined
      as a birthweight < 10th percentile) or placental mediated disease (defined as the
      presence of SGA, preeclampsia or gestational hypertension) in the following
      generation. RESULTS: Descendants from SGA adults presented lower birthweight
      percentile (median 26 [interquartile range 7-52] vs. 43 [19-75]; p<0.001) and
      higher prevalence of SGA (40.3% vs. 16.3%; p=0.001) and placental mediated
      disease (43.1% vs. 17.5%; p=0.001). After adjustment for confounder variables,
      parental SGA background was associated with an almost three-fold increased risk
      of subsequent SGA or any placental mediated disease in the following generation.
      This association was stronger in SGA mothers as compared to fathers. CONCLUSIONS:
      Our data provides evidence suggesting a transgenerational transmission of SGA
      highlighting the importance of public health strategies for preventing
      intrauterine growth impairment. This article is protected by copyright. All
      rights reserved.

PMID- 30207014
TI  - Levator ani morphology and function in women who have sustained obstetric anal
      sphincter injuries.
AB  - OBJECTIVES: To estimate the prevalence and explore risk factors of levator ani
      muscle injury in women with clinically diagnosed obstetric anal sphincter
      injuries (OASIs). Secondly, we aimed to assess the association between levator
      injury and pelvic floor muscle contraction, anal incontinence (AI) and urinary
      incontinence (UI) in women with OASIs. METHODS: Cross-sectional study of 250
      women with OASIs, recruited from 2013 until 2015 in a tertiary referral centre at
      Croydon University Hospital, UK. AI symptoms were assessed using the modified St
      Mark's Incontinence Score and UI using the International Consultation on
      Incontinence modular Questionnaire for Urinary Incontinence - Short Form. All
      women underwent 3D/4D transperineal ultrasound at rest and at maximum pelvic
      floor contraction. Major levator injury was defined as a uni-or bilateral defect
      in all three central slices using tomographic ultrasound imaging. Muscle
      contraction was assessed using the Modified Oxford Scale (MOS) and measured on
      ultrasound as the proportional change of the anteroposterior (AP) levator hiatal
      diameter between rest and contraction. We used multivariable logistic regression
      to study risk factors for levator injury. Multivariable ANCOVA and Mann-Whitney U
      test were used to study difference in contraction and symptoms between women with
      intact and injured levator. RESULTS: 29.4% of women who previously sustained
      OASIs were found to have major levator injury. This was 23.6% after normal
      vaginal delivery, and 40.2% after operative vaginal delivery; adjusted odds ratio
      4.1 (95% CI 1.4-11.9), p=0.01. Levator injury was associated with weaker pelvic
      floor muscle contraction; adjusted mean difference for proportional change in AP
      difference 4.2 (95% CI 1.7 - 6.7) and MOS 0.5 (95% CI 0.2-0.9), p< 0.01. Symptoms
      were similar for women with intact and injured levator muscle. CONCLUSIONS:
      Operative vaginal delivery was a risk factor for levator injury in women with
      OASIs, and levator injury was associated with a weaker pelvic floor muscle
      contraction. Special attention is recommended for women with OASI and levator
      injury as they would be at high risk of future pelvic floor disorders. The
      benefits of implementation of an intensive, focused and structured pelvic floor
      rehabilitation program needs to be evaluated in these women. This article is
      protected by copyright. All rights reserved.

PMID- 30207015
TI  - A typology of prescription drug monitoring programs: a latent transition analysis
      of the evolution of programs from 1999 to 2016.
AB  - BACKGROUND AND AIMS: Prescription drug monitoring programs (PDMP), defined as
      state-level databases used in the United States that collect prescribing
      information when controlled substances are dispensed, have varied substantially
      between states and over time. Little is known about the combinations of PDMP
      features that, collectively, may produce the greatest impact on prescribing and
      overdose. We aimed to (1) identify the types of PDMP models that have developed
      from 1999 to 2016, (2) estimate whether states have transitioned across PDMP
      models over time and (3) examine whether states have adopted different types of
      PDMP models in response to the burden of opioid overdose. METHODS: A latent
      transition analysis of PDMP models based on an adaptation of nine PDMP
      characteristics classified by prescription opioid policy experts as potentially
      important determinants of prescribing practices and prescription opioid overdose
      events. RESULTS: We divided the time-period into three intervals (1999-2004, 2005
      09, 2010-16), and found three distinct PDMP classes in each interval. The classes
      in the first and second interval can be characterized as 'no/weak', 'proactive'
      and 'reactive' types of PDMPs, and in the third interval as 'weak', 'cooperative'
      and 'proactive'. The meaning of these classes changed over time: until 2009,
      states in the 'no/weak' class had no active PDMP, whereas states in the
      'proactive' class were more likely to proactively provide unsolicited information
      to PDMP users, provide open access to law enforcement, and require more frequent
      data reporting than states in the 'reactive' class. In 2010-16, the 'weak' class
      resembled the 'reactive' class in previous intervals. States in the 'cooperative'
      class in 2010-16 were less likely than states in the 'proactive' class to provide
      unsolicited reports proactively or to provide open access to law enforcement;
      however, they were more likely than those in the 'proactive' class to share PDMP
      data with other states and to report more federal drug schedules. CONCLUSIONS:
      Since 1999, US states have tended to transition to more robust classes of
      prescription drug monitoring programs. Opioid overdose deaths in prior years
      predicted the state's prescription drug monitoring program class but did not
      predict transitions between prescription drug monitoring program classes over
      time.

PMID- 30207016
TI  - Cervical instability in patients with Trisomy 21: The eternal gamble.
AB  - Patients with Trisomy 21 are particularly at risk of cervical instability due to
      ligamentous laxity and osseous abnormalities. Up to 30% of Trisomy 21 patients
      are affected by atlanto-axial or atlanto-occipital instability, but only 1%-2% of
      cases are symptomatic. The radiologic assessment of cervical instability is not
      unanimously considered mandatory. The dynamic cervical spine radiograph is the
      most common screening tool for ruling out cervical spine instability in patients
      with Trisomy 21, and it is often requested before surgery. Several measurements
      have been investigated to assess the presence and degree of cervical instability;
      however, no conclusive recommendations have been forthcoming. In daily practice,
      many anesthesiologists may provide anesthesia via such means as laryngoscopy and
      tracheal intubation during surgery, without any radiological investigations
      before surgery. This review focuses on the diagnostic and prognostic measures
      available to evaluate the presence and degree of cervical instability in patients
      with Trisomy 21 and to propose practical recommendations to be applied in
      clinical practice.

PMID- 30207018
TI  - Bronchiectasis: Treatment decisions for pulmonary exacerbations and their
      prevention.
AB  - Interest in bronchiectasis has increased over the past two decades, as shown by
      the establishment of disease-specific registries in several countries, the
      publication of management guidelines and a growing number of clinical trials to
      address evidence gaps for treatment decisions. This review considers the evidence
      for defining and treating pulmonary exacerbations, the approaches for eradication
      of newly identified airway pathogens and the methods to prevent exacerbations
      through long-term treatments from a pragmatic practice-based perspective. Areas
      for future studies are also explored. Watch the video abstract.

PMID- 30207017
TI  - van Manen's phenomenology of practice: How can it contribute to nursing?
AB  - Phenomenology of practice is a useful, rigorous way of deeply understanding human
      phenomena. Therefore, it allows research to be conducted into nursing's most
      sensitive and decisive aspects. While it is a widely used research approach and
      methodology in nursing, it is seldom addressed and made use of in its practical
      and applied value. This article aimed to approach the global outlook of van
      Manen's hermeneutic-phenomenological method to better understand its theoretical
      background and to address and support the contribution this method can make to
      nursing, if rigorously applied. For a professional discipline like nursing, van
      Manen's approach is especially interesting because, in addition to contributing
      to the body of knowledge of nursing, it provides a special kind of knowledge that
      allows nurses to act in a more reflective manner, and with tact and skill, in
      certain situations and relationships that arise in their daily practice. A more
      in-depth understanding of this research methodology may help nurse-researchers
      make good use of it and also harness knowledge derived from this type of
      research. This comes as a result of assuming that phenomenological texts, the
      final product of the research, have tremendous educational potential for people
      who read them carefully.

PMID- 30207019
TI  - Efficacy of liposomal bupivacaine in pediatric patients undergoing spine surgery.
AB  - BACKGROUND: Liposomal bupivacaine may be an option for reducing opioid
      utilization in pediatric scoliosis surgery. The use of liposomal bupivacaine in
      this patient population has not been previously described. METHODS: Patients who
      underwent posterior spinal fusion surgery at our institution from 2011-2016 were
      identified. We performed a retrospective matched cohort study, matching patients
      who received intraoperative liposomal bupivacaine by age, gender, and extent of
      surgery to patients who did not. The primary endpoint was the use of morphine
      equivalents in the first 72 hours after surgery. Data collection included
      demographic and surgical data, pain medication utilization, and pain scores. Area
      under the curve (AUC) for pain scores was calculated. Descriptive statistical
      methods and univariable analysis were used to compare patients who received
      liposomal bupivacaine to patients who did not. RESULTS: One hundred and forty-one
      patients met study criteria; 47 patients who received liposomal bupivacaine were
      matched to 94 control patients who did not receive liposomal bupivacaine. No
      significant differences were noted in the patient population with the patients
      requiring a median of 11 segments (range 10-13 segments) fused. Patients received
      a mean of 56.6 +/- 37.4 mg/kg of intravenous acetaminophen, a mean of 3.4 +/- 2.1
      mg/kg of intravenous ketorolac, and 1.9 +/- 0.93 mg/kg of morphine equivalents in
      the first 72 hours after surgery. On univariable analysis, no differences were
      noted in intravenous acetaminophen use, pain score AUC, intravenous ketorolac
      use, or morphine equivalents (2.0 +/- 98 vs 1.8 +/- 0.82) in patients who did not
      receive liposomal bupivacaine as compared to those patient who did received
      liposomal bupivacaine. CONCLUSION: Liposomal bupivacaine was not associated with
      reductions in postoperative opioid use in pediatric spinal surgery.

PMID- 30207021
TI  - 3D-Printed Carbon Electrodes for Neurotransmitter Detection.
AB  - Implantable neural microsensors have significantly advanced neuroscience
      research, but the geometry of most probes is limited by the fabrication methods.
      Therefore, new methods are needed for batch-manufacturing with high
      reproducibility. Herein, a novel method is developed using two-photon
      nanolithography followed by pyrolysis for fabrication of free-standing
      microelectrodes with a carbon electroactive surface. 3D-printed spherical and
      conical electrodes were characterized with slow scan cyclic voltammetry (CV).
      With fast-scan CV, the electrodes showed low dopamine LODs of 11+/-1 nm (sphere)
      and 10+/-2 nm (cone), high sensitivity to multiple neurochemicals, and high
      reproducibility. Spherical microelectrodes were used to detect dopamine in a
      brain slice and in vivo, demonstrating they are robust enough for tissue
      implantation. This work is the first demonstration of 3D-printing of free
      standing carbon electrodes; and the method is promising for batch fabrication of
      customized, implantable neural sensors.

PMID- 30207020
TI  - IR Signature of Size-Selective CO2 Activation on Small Platinum Cluster Anions,
      Ptn - (n=4-7).
AB  - Infrared multiple photon dissociation spectroscopy (IR-MPD) has been employed to
      determine the nature of CO2 binding to size-selected platinum cluster anions, Ptn
      - (n=4-7). Interpreted in conjunction with density functional theory simulations,
      the results illustrate that the degree of CO2 activation can be controlled by the
      size of the metal cluster, with dissociative activation observed on all clusters
      n>=5. Of potential practical significance, in terms of the use of CO2 as a useful
      C1 feedstock, CO2 is observed molecularly-bound, but highly activated, on the Pt4
      - cluster. It is trapped behind a barrier on the reactive potential energy
      surface which prevents dissociation.

PMID- 30207022
TI  - Management of clinical and subclinical actinic keratoses with histological and
      immunohistochemical assessments by confocal microscopy.
AB  - Reflectance confocal microscopy has been used to monitor treatment efficacy in
      non-melanoma skin cancer, but few studies have compared different therapies using
      the same confocal criteria. We compare a single score designed in previous study
      to evaluate confocal, histological, and immunohistochemical results obtained
      before and after two treatments of actinic keratosis (AK) and in field
      cancerisation area. Thirty volunteer male patients, aged >50-year old, with at
      least three clinically visible AKs on the bald scalp, were included in this
      study: 15 patients were submitted to 3% diclofenac therapy and 15 to 5%
      fluorouracil therapy. Confocal imaging was performed on a 5 * 5 cm skin area. In
      five patients of each group we performed cutaneous biopsies. Scaling, upper
      nucleated cells, and inflammatory cells showed a higher percentage reduction in
      field cancerisation, especially in diclofenac treatment group, while in AK
      inflammatory cells showed a greater percentage reduction in 5-fluorouracil
      treatment group. Both therapies are efficacious, but their effectiveness is
      different on the single parameters of the confocal, histology,
      immunohistochemically.

PMID- 30207023
TI  - Effects of VEGF-ANG-1-PLA nano-sustained release microspheres on proliferation
      and differentiation of ADSCs.

PMID- 30207024
TI  - Vaccines in pediatric transplant recipients-Past, present, and future.
AB  - Infections significantly impact outcomes for solid organ and hematopoietic stem
      cell transplantation in children. Vaccine-preventable diseases contribute to
      morbidity and mortality in both early and late posttransplant time periods.
      Several infectious diseases and transplantation societies have published
      recommendations and guidelines that address immunization in adult and pediatric
      transplant recipients. In many cases, pediatric-specific studies are limited in
      size or quality, leading to recommendations being based on adult data or mixed
      adult-pediatric studies. We therefore review the current state of evidence for
      selected immunizations in pediatric transplant recipients and highlight areas for
      future investigation. Specific attention is given to studies that enrolled only
      children.

PMID- 30207025
TI  - Helium Tagging of Protonated Methane in Messenger Spectroscopy: Does It Interfere
      with the Fluxionality of CH5 + ?
AB  - Messenger infrared predissociation spectroscopy is an powerful technique to
      investigate elusive molecules. Despite accumulating evidence that 4 He-tagging
      has a minor effect on structure due to its weak interactions, its impact on
      intramolecular large-amplitude motion is much less clear. Using one of the most
      floppy molecules known, protonated methane, we investigate to what extent helium
      tags perturb its salient fluxionality, underlying full hydrogen scrambling.
      Bosonic path integral quantum simulations show that the impact of attaching up to
      four 4 He messengers to CH5 + is negligible compared to the non-tagged bare
      species. This non-invasive nature is unrelated to the bosonic character of 4 He.
      Yet, hydrogen scrambling has a pronounced effect on the microsolvation shell
      pattern of CH5 + ?Hen that emerges as a result of tagging. These findings should
      provide impetus to explore the power of He-tagging, particularly in the realm of
      weakly bound intermolecular complexes.

PMID- 30207026
TI  - Prognostic value of retrieved lymph node counts in patients with node-negative
      perihilar cholangiocarcinomas.
AB  - BACKGROUND: This study aimed to find out the prognostic value and optimal cut-off
      value of retrieved lymph node (LN) counts in patients with node-negative
      perihilar cholangiocarcinomas. METHODS: The Surveillance, Epidemiology and End
      Results (SEER) database was used to screen out patients with perihilar
      cholangiocarcinoma. The cut-off number of retrieved LNs was determined by the X
      tile programme. Kaplan-Meier methods with log-rank tests and Cox regression
      analysis were used for survival analysis. RESULTS: A total of 778 patients with
      perihilar cholangiocarcinoma (2004-2014) met the inclusion criteria for this
      research, and there were 403 patients without LN metastases (N0) among them. The
      cut-off numbers of retrieved LNs, which were determined using the X-tile
      programme, were 8 and 18. Both results of univariate and multivariate survival
      analyses in N0 patients showed that patients with >=18 retrieved LNs had a
      significantly better survival rate than patients with 1-7 retrieved LNs and
      patients with 8-17 retrieved LNs. In the subgroup of patients with early-stage
      tumours, patients with at least 13 retrieved LNs had a significantly better
      overall and cancer-specific survival than patients with fewer retrieved LNs.
      CONCLUSIONS: The retrieved LN counts are an independent prognostic factor for
      patients with node-negative perihilar cholangiocarcinoma. Patients with at least
      18 retrieved LNs had a better overall and cancer-specific survival than patients
      with fewer retrieved LNs. The minimum requirement for retrieving of LNs should
      reach 18 in perihilar cholangiocarcinoma.

PMID- 30207027
TI  - Rituximab for the treatment of autoimmune subepidermal blistering diseases.

PMID- 30207028
TI  - Construction of Porous Mo3 P/Mo Nanobelts as Catalysts for Efficient Water
      Splitting.
AB  - A novel synthesis strategy is demonstrated to prepare Mo3 P/Mo nanobelts with
      porous structure for the first time. The growth and formation mechanism of the
      porous Mo3 P/Mo nanobelt structure was disclosed by varying the contents of H2
      /PH3 and the reaction temperature. During the hydrogen evolution reaction (HER)
      catalysis, the optimized porous Mo3 P/Mo nanobelts exhibited a small
      overpotential of 78 mV at a current density of 10 mA cm-2 and a low Tafel slope
      of 43 mV dec-1 , as well as long-term stability in alkaline media, surpassing Pt
      wire. Density functional theory (DFT) calculations reveal that the H2 O
      dissociation on the surface of Mo3 P is favorable during the HER.

PMID- 30207030
TI  - Review of epiglottitis in the post Haemophilus influenzae type-b vaccine era.
AB  - BACKGROUND: This study reviewed the demographics, presentation, management,
      complications and outcomes of acute epiglottitis post Haemophilus influenzae type
      b vaccine introduction in Australia. METHODS: Retrospective review of acute
      epiglottitis at four Victorian tertiary centres from 2011 to 2016 was conducted.
      Patient characteristics, presentation, investigations, management, complications
      and outcomes were recorded. Subgroup analysis aiming to identify risk factors for
      patients requiring acute airway management was performed. RESULTS: Eighty-seven
      adult and six paediatric cases were identified. The most frequent clinical
      findings in adults were sore throat (88.5%), dysphagia (71.3%), odynophagia
      (57.5%), dysphonia (56.3%) and fever (55.2%); 75.9% required intensive care unit
      admission. Airway compromise requiring intubation occurred in 27.6%, with 12.5%
      of these patients undergoing emergency surgical airways. Stridor, hypoxia,
      shortness of breath, odynophagia and lymphadenopathy were statistically more
      frequent amongst cases requiring airway intervention (P < 0.05). Cultures
      revealed mixed results with no aetiological pattern. H. influenzae type-b was
      never cultured. Amongst paediatric cases, fever, tachycardia and stridor were
      frequently observed and all were admitted to intensive care unit. Two of six
      required intubation and one underwent surgical intervention. There were no
      deaths, but one patient suffered a hypoxic brain injury. CONCLUSION: Modern
      epiglottitis is not the disease previously encountered by clinicians. With
      changing demographics and varying organisms, management is adapting to reflect
      this. Complications are rare, and symptomatology at presentation aids earlier
      recognition of patients who may require airway protection.

PMID- 30207031
TI  - Role of post-operative serum C-reactive protein levels as a predictor of
      complications in upper gastrointestinal surgery.
AB  - BACKGROUND: This study was undertaken to assess the value of C-reactive protein
      (CRP) in predicting infective complications after elective upper gastrointestinal
      surgery. METHODS: Demographic data, clinical outcomes and serial CRPs
      preoperatively to post-operative day (POD) 7 were collected for patients
      undergoing pancreatectomy, hepatectomy and oesophago-gastrectomy between 2005 and
      2016. Areas under the curve (AUC) were used to evaluate diagnostic accuracy per
      day of measurement. RESULTS: Of the 249 patients, 63 (25.3%) developed infective
      complications and 25 (10%) developed severe infective complications (>=Clavien
      Dindo Grade III). Patients with infective complications trended towards higher
      CRP levels on POD1-POD4 and had significantly higher CRP levels on POD5 (156
      versus 114 mg/dL; P = 0.03), POD6 (146 versus 93 mg/dL; P < 0.01) and POD7 (135
      versus 84.6 mg/dL; P < 0.01). CRP had the best diagnostic accuracy for severe
      infective complications on POD6 (AUC: 0.73) and POD7 (AUC: 0.63). A CRP cut-off
      of 120 mg/dL on POD6 had a negative predictive value of 96.1% and a CRP cut-off
      of 80 mg/dL on POD7 had a negative predictive value of 94.9%. CONCLUSION: CRP
      measurements can be used as a negative predictive marker of infective
      complications in the first post-operative week after major elective upper
      gastrointestinal surgery.

PMID- 30207032
TI  - Posture-dependent thoracic outlet syndrome due to a inferiorly and dorsally
      angulated clavicle fracture.

PMID- 30207029
TI  - PHLDA1, another PHLDA family protein that inhibits Akt.
AB  - The PHLDA family (pleckstrin homology-like domain family) of genes consists of 3
      members: PHLDA1, 2, and 3. Both PHLDA3 and PHLDA2 are phosphatidylinositol (PIP)
      binding proteins and function as repressors of Akt. They have tumor suppressive
      functions, mainly through Akt inhibition. Several reports suggest that PHLDA1
      also has a tumor suppressive function; however, the precise molecular functions
      of PHLDA1 remain to be elucidated. Through a comprehensive screen for p53 target
      genes, we identified PHLDA1 as a novel p53 target, and we show that PHLDA1 has
      the ability to repress Akt in a manner similar to that of PHLDA3 and PHLDA2.
      PHLDA1 has a so-called split PH domain in which the PH domain is divided into an
      N-terminal (beta sheets 1-3) and a C-terminal (beta sheets 4-7 and an alpha
      helix) portions. We show that the PH domain of PHLDA1 is responsible for its
      localization to the plasma membrane and binding to phosphatidylinositol. We also
      show that the function of the PH domain is essential for Akt repression. In
      addition, PHLDA1 expression analysis suggests that PHLDA1 has a tumor suppressive
      function in breast and ovarian cancers.

PMID- 30207033
TI  - Divergent Reactivity of Stannane and Silane in the Trifluoromethylation of PdII :
      Cyclic Transition State versus Difluorocarbene Release.
AB  - The transmetalation is a key elementary step in cross-coupling reactions. Yet,
      the precise nature of its mechanism and transition state geometry are frequently
      elusive. This report discloses our study of the transmetalation of [PdII ]-F
      complexes with the silane- and stannane-based trifluoromethylation agents, R3
      SiCF3 and R3 SnCF3 . A divergent reactivity was uncovered, with the stannane
      showing selective R-group transfer, and the silane selective CF3 -group transfer.
      Using a combined experimental and computational approach, we uncovered a hitherto
      unrecognized transmetalation mechanism with the widely employed R3 SiCF3 reagent,
      explaining its unique activity in metal-catalyzed trifluoromethylations. While
      the stannane reacts via a cyclic, 4-membered transition state, the silane
      undergoes a fundamentally different pathway and releases a difluorocarbene in the
      transmetalation event. Molecular dynamics studies clearly reinforced the
      liberation of a free CF2 carbene, which reacts with [PdII ]-F to ultimately
      generate [PdII ]-CF3.

PMID- 30207034
TI  - Too frail for surgery? A frailty index in major colorectal surgery.
AB  - BACKGROUND: Frailty is defined as increased vulnerability from accumulating
      morbidities in multiple organ systems. Evidence suggests frailty indices predict
      surgical outcomes in elderly patients. We assessed the validity of a frailty
      index in predicting post-operative outcomes in major colorectal surgery. METHODS:
      A retrospective review of a prospective database was studied. Patients aged less
      than 65 years were excluded. Patients were assessed using a validated National
      Surgical Quality Improvement Program frailty index. Endpoints included intensive
      care unit (ICU) stay, post-operative complications and 30-day post-operative
      mortality, and also compared using American Society of Anesthesiologists (ASA)
      grade and P-Possum CR. RESULTS: Of the 205 patients, 43 (21%) were frail and 162
      (79%) were not frail. Seven percent of frail patients required ICU stay compared
      with 6% non-frail patients (P > 0.05, NS). P-Possum in frail versus non-frail
      groups in ICU was 48% versus 8.6% (P < 0.05). Forty percent of frail and 26% non
      frail patients developed post-operative complications (P > 0.05, NS) with mean P
      Possum of 23% versus 12% in these groups, respectively (P < 0.05). Five percent
      of frail patients and 2.5% non-frail patients died within 30 days of surgery (P >
      0.05, NS) with a mean P-Possum of 43% versus 7% in these groups, respectively (P
      > 0.05, NS). CONCLUSIONS: These data demonstrate that frail patients who
      developed complications, died within 30 days and required admission to ICU had
      significantly higher P-Possum CR scores. However, the P-Possum CR score is a
      superior predictor of post-operative outcomes than frailty index alone.

PMID- 30207035
TI  - Incidence and trend of type 1 diabetes and the underlying environmental
      determinants.
AB  - A wealth of epidemiological studies concerning the distribution of type 1
      diabetes (T1D) around the world have pointed to the appreciable variation in the
      incidence of T1D among disparate age groups, ethnicities, and geographical
      locations. On the whole, the incidence of childhood T1D has been on the rise, and
      a plausible inverse relationship between the initial incidence rate and the
      following annual increase in incidence has been raised. Countries that used to
      exhibit lower incidences tend to have steep annual increase whereas those with
      already-established high incidences are more likely to show a modest increase or
      even stabilization in T1D incidence. Environmental agents considered responsible
      for the current evolving pattern of T1D incidence will be detailed, mainly
      including the increasing prevalence of childhood obesity, viral infections in a
      chronic manner, maternal-child interaction such as breastfeeding, and latitude
      ultraviolet B-vitamin D pathway. Certain rationale has been put forward in an
      attempt to explain the potential association between environmental agents and
      development of T1D. For instance, accelerator hypothesis regards insulin
      resistance as the promoter of earlier disease onset in obese children whereas the
      negative correlation of microbial infections in background populations with
      incidence of T1D represents the basic component of the hygiene hypothesis.
      Further investigations are still warranted to verify these theories across
      multiple ethnic groups and to identify additional contributors to the variation
      in T1D incidence.

PMID- 30207037
TI  - Corrigendum.

PMID- 30207036
TI  - Oesophagectomy at a New Zealand regional centre: where to now?
AB  - BACKGROUND: This study aims to define contemporary trends in characteristics,
      costs and management of patients diagnosed with oesophageal adenocarcinoma in New
      Zealand. METHODS: Clinical, pathological and management data of the 135 patients
      presenting with histologically proven adenocarcinoma to our institution over a 5
      year period (January 2010 to December 2014) was collected. Primary analysis
      reviewed patient demographics, co-morbidities, treatment strategy and survival.
      Secondary analysis defined operative outcomes including complications, mortality
      rates and overall survival to December 2016. RESULTS: Thirty-eight patients
      underwent oesophago-gastrectomy (resection rate 28%) with curative intent
      following neoadjuvant chemotherapy with Clavien-Dindo >=3 complications in 17
      patients (46%). Actuarial survivals from surgery at 1, 3 and 5 years were (79, 55
      and 50%), with 19 patients (54%) alive and disease free at a median follow-up of
      26.5 months (range 1-82 months). Overall, this represented one sixth of the
      national volume of oesophagectomy. Ninety-seven patients were managed non
      surgically due to metastatic or advanced local disease (n = 64), co-morbid status
      (n = 27), patients choice (n = 2) and unknown (n = 4). Median survival from
      diagnosis in non-resected patients was 9 months (range 1-40 months). CONCLUSION:
      Oesophagectomy remains a challenging procedure for any institution, although good
      results can be achieved. Foci for referral are emerging in New Zealand for the
      surgical management of oesophageal cancer.

PMID- 30207038
TI  - Ileo-ileal knot: a rare cause of acute intestinal obstruction.

PMID- 30207039
TI  - Assessment of local tissue water in the arms and trunk of breast cancer survivors
      with and without upper extremity lymphoedema.
AB  - Given the paucity of information on local tissue water (LTW) in the upper
      extremity and trunk of women after breast cancer surgery, the purpose of this
      study was to compare tissue dielectric constant (TDC) values between the affected
      and unaffected sides of breast cancer survivors with and without upper extremity
      lymphoedema (LE). Differences in LTW were assessed using the TDC method for three
      sites in the upper limbs, three sites in the lateral thorax and two sites on the
      back. Additional measures included demographic and clinical characteristics, arm
      circumference and bioimpedance analysis. For the 112 survivors without LE, no
      differences in TDC values were found between the affected and unaffected sides
      for the first dorsal web space, ventral forearm and upper arm, and upper and
      lower back. Compared to the unaffected side, TDC values were significantly higher
      on the affected side for the upper, mid and lower lateral thorax. For the 78
      survivors with LE, compared to the unaffected side, TDC was significantly higher
      on the affected side for all of the sites evaluated except the hand web space.
      Our findings support the use of the TDC method to detect differences in upper
      extremity and truncal oedema in survivors with LE following breast cancer
      treatment. Measurement of LTW may provide a useful method to determine truncal as
      well as extremity LE. The ability to detect early signs of truncal oedema may
      lead to pre-emptive interventions in breast cancer survivors.

PMID- 30207040
TI  - Acute renal outcomes with sodium-glucose co-transporter-2 inhibitors: Real-world
      data analysis.
AB  - AIM: To assess the possible risk of acute kidney injury (AKI) with the use of
      sodium-glucose co-transporter-2 inhibitors (SGLT2-i) as well as changes in
      estimated glomerular filtration rate (eGFR), hospitalizations and mortality in a
      real-world setting. MATERIALS AND METHODS: Included in this historical cohort
      study were patients with type 2 diabetes in a large health organization in Israel
      who initiated therapy with SGLT2-i or dipeptidyl peptidase-4 inhibitors (DPP-4i)
      during 1 April 2015 to 30 June 2017. We collected data on serum creatinine
      measurements taken between 180 days prior to and 24 weeks after therapy
      initiation. Study endpoints included >=30% reduction in eGFR, hospitalization
      with AKI, any hospitalization and all-cause mortality. RESULTS: Overall 6418 and
      5604 patients initiated SGLT2-i and DPP-4i, respectively. Baseline mean (SD) eGFR
      was higher among the SGLT2-i group compared with the DPP-4i group (88.3 [17.4]
      and 82.8 [23.7], respectively) but were similar when stratifying by chronic
      kidney disease (CKD) stages. The adjusted odds ratio (OR) (95% confidence
      interval [CI]) for >=30% reduction in eGFR with SGLT2-i versus DPP4-i was 0.70
      (0.49-1.00) and ORs ranged from 1.97 (0.62-6.26) to 0.45 (0.21-0.99) in patients
      with baseline eGFR 30 to 45 and >=90 mL/min/1.73 m2 , respectively. Risks of AKI
      (OR = 0.47, 95% CI 0.27-0.80), hospitalization (OR = 0.66, 95% CI 0.56-0.78) or
      all-cause mortality (OR = 0.43, 95% CI 0.20-0.95) were lower in patients
      initiating SGLT2-i versus DPP-4i. CONCLUSIONS: This real-world data analysis
      supports reassuring findings from previous randomized clinical trials showing no
      increased AKI risk among SGLT2-i users. Nevertheless, because of the more
      prominent decrease in eGFR in patients with moderate CKD, cautious use of SGLT2-i
      in patients with reduced eGFR is advised.

PMID- 30207041
TI  - Shanghai Time Outside to Reduce Myopia trial: design and baseline data.
AB  - IMPORTANCE: Myopia is a major public health concern worldwide, while outdoor time
      is indicated to be protective against the onset of myopia. BACKGROUND: To
      describe the methodology and baseline data of the Shanghai Time Outside to Reduce
      Myopia (STORM) trial. DESIGN: A 2-year, school-based, prospective, cluster
      randomized trial. PARTICIPANTS: Children from grade I and II classes of 24
      schools from eight districts in Shanghai, China, were randomized to either a
      control group, a test group I (40-min outdoor time/day) or test group II (80-min
      outdoor time/day). METHODS: At baseline and annual intervals, cycloplegic
      autorefraction and axial length measurement will be performed. Time outdoors and
      light exposure will be monitored via parent/carer questionnaires and a wearable
      device. MAIN OUTCOME MEASURES: Spherical equivalent, prevalence of myopia and
      time outdoors in each group. RESULTS: A total of 6295 eligible children (age 7.2
      +/- 0.7 y [6-9 y]) were randomized to control (n = 2037), test group I (n = 2329)
      and test group II (n = 1929). At baseline, spherical equivalent was +0.98 +/-
      1.02D, +1.02 +/- 1.02D and +1.00 +/- 0.99D (P = 0.708), myopia prevalence was
      8.9, 7.7 and 7.8% (P = 0.270) and time outdoors was 58.5 +/- 35.8, 59.8 +/- 34.7
      and 58.5 +/- 35.3 min/d (P = 0.886) for control, test groups I and II,
      respectively. CONCLUSIONS AND RELEVANCE: Myopia prevalence was high at nearly 8
      to 9% in school children aged 7 years in Shanghai, China. The current trial will
      help evaluate if increased time outdoors has a role to play in reducing the
      incidence of myopia and/or slow the progression of myopia.

PMID- 30207042
TI  - Comparative risk of genital infections associated with sodium-glucose co
      transporter-2 inhibitors.
AB  - The extent to which sodium-glucose co-transporter-2 (SGLT2) inhibitors increase
      the risk of genital infections in routine clinical care, compared with other
      antidiabetic medications, is not clear, or whether the increased risk is
      consistent across gender or age subgroups, within individual SGLT2 agents, or if
      it is more pronounced at a particular time after treatment initiation. We
      conducted a retrospective cohort study using two US commercial claims databases
      (2013-2017). In the primary analysis, 1:1 propensity score-matched cohorts of
      female and male subjects with type 2 diabetes mellitus initiating SGLT2 versus
      dipeptidyl peptidase-4 inhibitors were created. The outcome was a composite of
      genital candidal infections, vaginitis or vulvovaginitis in women, and genital
      candidal infections, balanitis, balanoposthitis, phimosis or paraphimosis in men.
      Among propensity score-matched cohorts of 129 994 women and 156 074 men, the
      adjusted hazard ratio (HR) and excess risk per 1000 person-years for SGLT2 versus
      DPP-4 inhibitors was 2.81 (95% confidence interval [CI], 2.64, 2.99) and 87.4
      (95% CI, 79.1, 96.2) respectively for women, and was 2.68 (95% CI, 2.31, 3.11)
      and 11.9 (95% CI, 9.3-15.0) for men. Findings were similar in the SGLT2 inhibitor
      versus GLP-1 agonist comparison, more pronounced in the subgroup of patients aged
      >=60 (HR, 4.45 [95% CI, 3.83-5.17] in women and 3.30 [95% CI, 2.56-4.25] in men),
      and no meaningful difference across individual SGLT2 inhibitors was identified.
      This increase in risk was evident in the first month of treatment initiation and
      remained elevated throughout the course of therapy. SGLT2 inhibitors were
      associated with an approximately 3-fold increase in risk of genital infections.

PMID- 30207043
TI  - Visual symptoms following iridotomy.

PMID- 30207044
TI  - Letter to the Editor on "Antecedent rest may not be necessary for automated
      office blood pressure at lower treatment targets".

PMID- 30207045
TI  - Tofacitinib as the potent treatment for refractory pemphigus: A possible
      alternative treatment for pemphigus.
AB  - Pemphigus is a rare, but life-threatening autoimmune disease with a high rate of
      morbidity and mortality, if left untreated. After the development of
      corticosteroid therapy in the 1950s, the death rate for pemphigus has
      significantly decreased. However, finding more potent therapeutic options for
      refractory patients has remained a controversial topic. In the recent years,
      rituximab has increasingly been used for the treatment of refractory pemphigus,
      but some patients do not well-respond. In addition, there is a paucity of
      evidence to support the risk of diseases exacerbation after rituximab therapy. In
      this study, as a JAK1 and JAK3 inhibitor, tofacitinib has been proposed for the
      treatment of refractory pemphigus patients.

PMID- 30207046
TI  - A pilot study of hormonal contraceptive use and bone mineral density in young
      women with sickle cell disease.

PMID- 30207047
TI  - Impact of an acute surgical unit on outcomes in acute cholecystitis.
AB  - BACKGROUND: The acute surgical unit (ASU) model has been associated with improved
      outcomes for emergency general surgical patients. Few Australasian studies have
      investigated patients with cholecystitis and none from South Australia. METHODS:
      A retrospective cohort study compared patients admitted to our institution with
      acute cholecystitis during the 2 years before (traditional period) and after (ASU
      period) introduction of an ASU on 1 August 2012. Primary outcomes were length of
      stay, rates of definitive surgery on index admission, time to definitive surgery
      and proportion of cases performed in-hours. Secondary outcomes were time from
      emergency department referral to admission, time from radiologically confirmed
      diagnosis to theatre start, rates of conversion to open cholecystectomy,
      complications and cholelithiasis-related representations while awaiting
      definitive procedure. RESULTS: A total of 319 patients met the inclusion
      criteria; 172 and 147 pre- and post-ASU introduction, respectively. Compared with
      the traditional period, ASU patients had shorter length of stay (3.80 versus 2.83
      days, P < 0.0001), higher rates of surgery on index admission (70.9% versus
      95.3%, P < 0.0001), shorter time to definitive surgery (28.1 versus 22.1 days, P
      < 0.001), lower rates of conversion to open cholecystectomy (18.0% versus 7.1%, P
      = 0.007) and fewer complications (24.4% versus 6.1%, P < 0.0001). Other outcomes
      were not significantly different. CONCLUSION: Introduction of an ASU was
      associated with superior outcomes amongst patients admitted with acute
      cholecystitis. These findings extend the literature in support of the current
      model of care.

PMID- 30207048
TI  - Burkitt lymphoma in Iraqi children: A distinctive form of sporadic disease with
      high incidence of EBV+ cases and more frequent expression of MUM1/IRF4 protein in
      cases with head and neck presentation.
AB  - Epstein-Barr virus (EBV)-related lymphoproliferative disorders are relatively
      common in Iraqi children. Burkitt lymphoma (BL) accounted for 40% of lymphoma
      cases. The mean age of 125 BL cases was 5.9 +/- 3.1 years, and the male-to-female
      ratio was 3.6:1. Clinical presentation was abdominal in 66% and head and neck in
      34%. Bone marrow involvement was higher (P < 0.001) in children with head and
      neck disease. Tumor cells had MYC translocation (96%) and were CD20+ /CD10+ /MYC+
      /BCL2- . MUM1/IRF4 staining was expressed by a fraction of tumor cells in 19 of
      125 cases (15%) and was more frequent (P < 0.007) in head and neck disease
      (12/42; 29%). EBV-encoded RNA was positive in 100 of 125 (80%) BL cases.

PMID- 30207049
TI  - Integrating laboratory and field studies to assess impacts of discharge from a
      uranium mine and validate a water quality guideline value for magnesium.
AB  - Magnesium (Mg) is a primary contaminant in mine water discharges from the Ranger
      Uranium Mine (north Australia). Site-specific water quality guideline values
      (WQGVs) for Mg have been derived from laboratory and field studies. Contaminated
      groundwater with elevated electrical conductivity and metals (Mg, Mn, U, SO4 ,
      and Ca) was detected flowing from the mine site into adjacent surface waters.
      This provided an opportunity to investigate the protectiveness of the Mg WQGV by
      conducting an integrated laboratory and field study. A direct toxicity assessment
      (DTA) of the groundwater was conducted with local tropical freshwater species:
      duckweed (Lemna aequinoctialis), green hydra (Hydra viridissima), and the aquatic
      snail Amerianna cumingi. An in situ toxicity assessment was carried out in the
      creek receiving diluted groundwater by use of the same species of snail, to aid
      interpretation of laboratory-derived data. The toxicity of the contaminated
      groundwater was higher than Mg-only toxicity testing for H. viridissima, with
      other elevated metals and major ions contributing to toxicity. However, for
      duckweed and snail, the contaminated groundwater was less toxic than the Mg-only
      testing. In situ snail monitoring supported laboratory exposures, showing no
      effect on reproduction of A. cumingi exposed to an average of approximately 5
      mg/L Mg; however, a very small effect was noted closer to the groundwater source,
      probably associated with other contaminants. The minimal toxicity observed for L.
      aequinoctialis and A. cumingi, despite the elevated Mg, can be explained by the
      high calcium (Ca) concentration of the water and the potential amelioration of
      metal toxicity. The extent of Ca amelioration of Mg toxicity was organism
      dependent. This study affirms the proposed environmental rehabilitation standard
      of 3 mg/L Mg for surface waters with a Ca concentration typical of water from
      this mine site. Integr Environ Assess Manag 2018;00:000-000. (c) 2018 SETAC.

PMID- 30207050
TI  - Effective response to azacitidine in a child with a second relapse of myeloid
      leukemia associated with Down syndrome after bone marrow transplantation.

PMID- 30207051
TI  - The Energy Requirements for Flow-Induced Solidification of Silk.
AB  - Natural silk spinning has undergone strong selection for resource efficiency and
      thus presents a biomimetic ideal for fiber production. Industrial replication of
      natural silk fibers would enable access to low energy, cost-efficient processing,
      but is hampered by a lack of understanding surrounding the conversion of liquid
      feedstock into a solid fiber as a result of flow. Previously, shear stress, shear
      rate, or time have been presented as criteria for silk fiber formation, but here
      it is proposed that spinning requires carefully balancing all three, and is a
      result of controlled energy accumulation in the feedstock. To support this
      hypothesis, rheology is used to probe the energy required for conversion, compare
      differences between amorphous solid and ordered fiber production and explain the
      energetic penalty the latter demands. New definitions of what constitutes an
      artificial silk fiber are discussed, along with methods to ensure that each
      spinning criterion is met during biomimetic spinning.

PMID- 30207052
TI  - Immunoglobulin prophylaxis in pediatric hematopoietic stem cell transplant.
AB  - BACKGROUND: After allogeneic hematopoietic stem cell transplantation (HSCT),
      patients have an increased susceptibility to infections, thought to be due in
      part to hypogammaglobulinemia. Thus, prophylactic administration of intravenous
      immunoglobulins (IVIG) has been administered to patients after HSCT as standard
      of care. This study compares the viral infection rate between dosing IVIG by IgG
      levels versus by routine monthly administration in pediatric patients after HSCT.
      PROCEDURE: In this retrospective chart review, we abstracted from electronic
      medical records data on pediatric patients undergoing HSCT from 2010 to 2012 for
      6 months post-HSCT. We compared rates of infection between patients treated with
      routine IVIG prophylaxis and patients given IVIG prophylaxis based on IgG tough
      levels (IgG levels were checked every 2 weeks). RESULTS: Data were available and
      reviewed for 50 patients dosed with IVIG every 28 days (Group 1) and 100 patients
      dosed with IVIG based on IgG level > 400 mg/dl (Group 2). There was no
      significant difference in age (P = 0.98) or sex (P = 0.42), reason for HSCT,
      alemtuzumab use (P = 0.602), or reduced intensity conditioning (P = 1.00).
      Significantly more haploidentical donors were in Group 1 (P = 0.04), otherwise
      there was no significant difference in donor type between groups. Significantly
      less acute graft versus host disease occurred (P = <0.001) in Group 2 (P =
      <0.001). PCR documented viral infections were not significantly different (P =
      0.412) (Table 1). Group 2 patients received significantly less IVIG (P < 0.001).
      CONCLUSION: Dosing IVIG to maintain an IgG level > 400 mg/dl is a cost-effective
      and safe way to prevent viral infections in pediatric patients undergoing HSCT.

PMID- 30207053
TI  - Impact of a novel exponential weighted 4DCT reconstruction algorithm.
AB  - PURPOSE: This work characterizes a novel exponential 4DCT reconstruction
      algorithm (EXPO), in phantom and patient, to determine its impact on image
      quality as compared to the standard cosine-squared weighted 4DCT reconstruction.
      METHODS: A motion platform translated objects in the superior-inferior (S-I)
      direction at varied breathing rates (8-20 bpm) and couch pitches (0.06-0.1) to
      evaluate interplay between parameters. Ten-phase 4DCTs were acquired and data
      were reconstructed with cosine squared and EXPO weighting. To quantify the
      magnitude of image blur, objects were translated in the anterior-posterior (A-P)
      and S-I directions for full-width half maximum (FWHM) analysis between both 4DCT
      algorithms and a static case. 4DCT sinogram data for 10 patients were
      retrospectively reconstructed using both weighting factors. Image subtractions
      elucidated intensity and boundary differences. Subjective image quality grading
      (presence of image artifacts, noise, spatial resolution (i.e., lung/liver
      boundary sharpness), and overall image quality) was conducted yielding 200
      evaluations. RESULTS: After taking static object size into account, the FWHM of
      EXPO reconstructions in the A-P direction was 3.3 +/- 1.7 mm (range: 0-4.9) as
      compared to cosine squared 9.8 +/- 4.0 mm (range: 2.6-14.4). The FWHM of objects
      translated in the S-I direction reconstructed with EXPO agreed better with the
      static FWHM than the cosine-squared reconstructions. Slower breathing periods,
      faster couch pitches, and intermediate 4DCT phases had the largest reductions of
      blurring with EXPO. 18 of 60 comparisons of artifacts were improved with EXPO
      reconstruction, whereas no appreciable changes were observed in image quality
      scores. In 18 of 20 cases, EXPO provided sharper images although the reduced
      projections also increased baseline noise. CONCLUSION: Exponential weighted 4DCT
      offers potential for reducing image blur (i.e., improving image sharpness) in
      4DCT with a tendency to reduce artifacts. Future work will involve evaluating the
      impact on treatment planning including delineation ability and dose calculation.

PMID- 30207054
TI  - Prevalence and nature of hearing loss in a cohort of children with sickle cell
      disease.
AB  - BACKGROUND: Sickle cell disease (SCD) may cause injury to any organ, including
      the auditory system. Although the association of SCD and hearing loss has been
      described, the nature of this complication is unknown. We sought to establish the
      prevalence and nature of hearing loss in a referred cohort of children with SCD
      and to identify correlating disease- or treatment-associated factors. PROCEDURE:
      We conducted a retrospective review of patients with SCD < 22 years of age who
      had hearing evaluations between August 1990 and December 2014. Demographics,
      audiograms, and disease and treatment variables were analyzed. RESULTS: Two
      hundred and ten audiograms among 81 patients were reviewed, and 189 were
      evaluable. Seventy-two children constituted the referred cohort. Fourteen (19.4%)
      had hearing loss documented on at least one audiogram. Seven (9.7%) patients had
      only conductive hearing loss, and the loss persisted for up to 10.3 years. The
      median age of first identification was eight years. Six (8.3%) patients had
      hearing loss that was at least partially sensorineural. One patient's hearing
      loss was ambiguous. All sensorineural hearing losses were unilateral and 4/6
      patients had prior documented normal hearing, indicating acquired loss. No
      correlations were identified. CONCLUSIONS: Both conductive and sensorineural
      hearing losses are more prevalent in our study population than those observed in
      the general pediatric population. In children with SCD, sensorineural hearing
      loss appears to be acquired and unilateral. Conductive hearing loss was
      identified in older children and can persist. Serial screening is needed for
      early detection and more prompt intervention in this population.

PMID- 30207055
TI  - Significance of CNS 2 cerebrospinal fluid status post-induction in pediatric and
      adolescent patients with acute lymphoblastic leukemia.
AB  - BACKGROUND: At diagnosis, there are prognostic implications of low-level leukemic
      blasts (CNS 2) in the cerebrospinal fluid (CSF) of patients with acute
      lymphoblastic leukemia (ALL). However, the significance of post-induction CNS 2
      results and the impact of equipment on CNS 2 prevalence have not been well
      studied. PROCEDURE: A single-institution retrospective cohort study was conducted
      to analyze the outcome of patients with >=1 post-induction CNS 2. A subanalysis
      compared the proportion of CNS 2 CSF results using 2 different cytocentrifuges;
      the Shandon Cytospin used from 2005 to 2008 and the Wescor Cytopro used from 2010
      to 2014. RESULTS: Over 4500 post-induction CSF samples were analyzed, of which 59
      were CNS 2. In covariate-adjusted analyses, post-induction CNS 2 did not
      significantly increase relapse risk. The proportion of CNS 2 results increased
      4.3-fold in noninfants and 6.3-fold in infants using the Wescor Cytopro.
      Cytocentrifuge machine did not affect CNS 3 prevalence. CONCLUSIONS: These
      findings support our current practice of not changing management based on a post
      induction CNS 2 CSF and highlight how equipment changes can significantly
      influence testing results. More data are needed to analyze relapse by
      subpopulations, such as those with repeated CNS 2 findings.

PMID- 30207056
TI  - Comment on: Olanzapine for chemotherapy-induced nausea: Lessons learned from
      child and adolescent psychiatry.

PMID- 30207059
TI  - A journey of exploration into the uterine cavity.

PMID- 30207060
TI  - The alleviation of pain: a surgical revolution.

PMID- 30207061
TI  - The death of the Princess Charlotte of Wales in 1817 was more likely due to
      pulmonary embolism than to postpartum haemorrhage.

PMID- 30207057
TI  - Effects of interleukin-17A in nucleus pulposus cells and its small-molecule
      inhibitors for intervertebral disc disease.
AB  - Intervertebral discs (IVD) degeneration, which is caused by ageing or mechanical
      stress, leads to IVD disease, including back pain and sciatica. The cytokine
      interleukin (IL)-17A is elevated in NP cells during IVD disease. Here we explored
      the pharmacotherapeutic potential of IL-17A for the treatment of IVD disease
      using small-molecule inhibitors that block binding of IL-17A to the IL-17A
      receptor (IL-17RA). Treatment of NP cells with IL-17A increased expression of
      cyclooxygenase-2 (COX-2), IL-6, matrix metalloproteinase (MMP)-3 and MMP-13.
      These increases were suppressed by an IL-17A-neutralizing antibody, and small
      molecules that were identified as inhibitors by binding to the IL-17A-binding
      region of IL-17RA. IL-17A signalling also altered sulphated glycosaminoglycan
      deposition and spheroid colony formation, while treatment with small-molecule
      inhibitors of IL-17A attenuated this response. Furthermore, mitogen-activated
      protein kinase pathways were activated by IL-17A stimulation and induced IL-6 and
      COX-2 expression, while small-molecule inhibitors of IL-17A suppressed their
      expression. Taken together, these results show that IL-17A is a valid target for
      IVD disease therapy and that small-molecule inhibitors that inhibit the IL-17A-IL
      17RA interaction may be useful for pharmacotherapy of IVD disease.

PMID- 30207062
TI  - Termination of pregnancy or abortion?

PMID- 30207063
TI  - Large-scale identification of functional microRNA targeting reveals cooperative
      regulation of the hemostatic system.
AB  - Essentials MicroRNAs (miRNAs) regulate the molecular networks controlling
      biological functions such as hemostasis. We utilized novel methods to analyze
      miRNA-mediated regulation of the hemostatic system. 52 specific miRNA
      interactions with 11 key hemostatic associated genes were identified.
      Functionality and drugability of miRNA-19b-3p against antithrombin were
      demonstrated in vivo. SUMMARY: Background microRNAs (miRNAs) confer robustness to
      complex molecular networks regulating biological functions. However, despite the
      involvement of miRNAs in almost all biological processes, and the importance of
      the hemostatic system for a multitude of actions in and beyond blood coagulation,
      the role of miRNAs in hemostasis is poorly defined. Objectives Here we
      comprehensively illuminate miRNA-mediated regulation of the hemostatic system in
      an unbiased manner. Methods In contrast to widely applied association studies, we
      used an integrative screening approach that combines functional aspects of miRNA
      silencing with biophysical miRNA interaction based on RNA pull-downs (miTRAP)
      coupled to next-generation sequencing. Results Examination of a panel of 27
      hemostasis-associated gene 3'UTRs revealed the majority to possess substantial
      Dicer-dependent silencing capability, suggesting functional miRNA targeting.
      miTRAP revealed 150 specific miRNA interactions with 14 3'UTRs, of which 52,
      involving 40 miRNAs, were functionally confirmed. This includes cooperative miRNA
      regulation of key hemostatic genes comprising procoagulant (F7, F8, F11, FGA, FGG
      and KLKB1) and anticoagulant (SERPINA10, PROZ, SERPIND1 and SERPINC1) as well as
      fibrinolytic (PLG) components. Bioinformatic analysis of miRNA functionality
      reveals established and potential novel links between the hemostatic system and
      other pathologies, such as cancer, bone metabolism and renal function.
      Conclusions Our findings provide, along with an in-vivo proof of concept, deep
      insights into the network of miRNAs regulating the hemostatic system and present
      a foundation for biomarker discovery and novel targeted therapeutics for
      correction of de-regulated hemostasis and associated processes in the future. A
      repository of the miRNA targetome covering 14 hemostatic components is provided.

PMID- 30207064
TI  - Central diabetes insipidus in pediatric patients with Langerhans cell
      histiocytosis: Results from the JLSG-96/02 studies.
AB  - PURPOSE: We analyzed central diabetes insipidus (CDI) development in pediatric
      patients with Langerhans cell histiocytosis (LCH) treated according to the Japan
      LCH Study Group (JLSG) regimen, which is the combination chemotherapy including
      cytarabine (Ara-C). METHODS: Retrospective data from 317 patients (multisystem
      disease (MS), n = 206; multiple focal bone (MFB), n = 111) treated according to
      the JLSG-96/02 regimens were analyzed. RESULTS: The median follow-up duration was
      10.6 years (range, 0.1-21.1). A total of 50/317 (15.8%) patients developed CDI
      (MFB, n = 4; MS, n = 46). Of the 50 cases, CDI was already present at the time of
      LCH diagnosis (pre-CDI) in 25, and it newly developed after the diagnosis and
      initiation of treatment (post-CDI) in the other 25 cases. The cumulative
      incidence of post-CDI at 10-year calculated by Kaplan-Meier analysis was 9.0% for
      total and 12.0% for MS patients. A positive correlation with LCH lesions at the
      CNS risk sites at diagnosis was found in pre-CDI cases (17/164 vs 8/171; P =
      0.0359), but not in post-CDI cases (14/129 vs 11/163; P = 0.254). Multivariate
      analysis showed that relapse at the CNS risk sites was significantly associated
      with post-CDI development (hazard ratio: 4.70; 95% CI, 1.29-17.1, P < 0.05).
      CONCLUSIONS: In the JLSG-96/02 studies, CDI developed in 15.8% of the cohort in
      which half as pre- and the other half as post-CDI. Relapse, particularly at the
      CNS risk sites, was linked with the development of post-CDI.

PMID- 30207065
TI  - CLARITY-BPA academic laboratory studies identify consistent low-dose Bisphenol A
      effects on multiple organ systems.
AB  - Bisphenol A (BPA) is a high-production chemical used in a variety of applications
      worldwide. While BPA has been documented as an endocrine-disrupting chemical
      (EDC) having adverse health-related outcomes in multiple studies, risk assessment
      for BPA has lagged due to reliance on guideline toxicology studies over academic
      ones with end-points considered more sensitive and appropriate. To address
      current controversies on BPA safety, the United States National Institute of
      Environmental Health Sciences (NIEHS), the National Toxicology Program (NTP) and
      the Food and Drug Administration (FDA) established the Consortium Linking
      Academic and Regulatory Insights on BPA Toxicity (CLARITY-BPA) using the NCTR
      Sprague-Dawley rats. The goal of CLARITY-BPA is to perform a traditional
      regulatory toxicology study (Core study) in conjunction with multiple
      behavioural, molecular and cellular studies by academic laboratories focused on
      previously identified BPA-sensitive organ systems (Academic studies). Combined
      analysis of the data from both study types will be undertaken by the NTP with the
      aim of resolving uncertainties on BPA toxicity. To date, the Core study has been
      completed and a draft report released. Most of the academic studies have also
      been finalized and published in peer-reviewed journals. In light of this
      important milestone, the PPTOX-VI meeting held in the Faroe Islands, 27-30 May
      2018 devoted a plenary session to CLARITY-BPA with presentations by multiple
      investigators with the purpose of highlighting key outcome. This MiniReview
      synthesizes the results of three academic studies presented at this plenary
      session, evaluates recently published findings by other CLARITY-BPA academic
      studies to provide an early combined overview of this emerging data and places
      this in the context of the Core study findings. This co-ordinated effort revealed
      a plethora of significant BPA effects across multiple organ systems and BPA doses
      with non-monotonic responses across the dose range utilized. Remarkably
      consistent across most studies, including the Core study, are low-dose effects
      (2.5, 25 and 250 MUg BPA/kg body-weight). Collectively, the findings highlighted
      herein corroborate a significant body of evidence that documents adverse effects
      of BPA at doses relevant to human exposures and emphasizes the need for updated
      risk assessment analysis.

PMID- 30207066
TI  - Protein disulfide isomerase regulation by nitric oxide maintains vascular
      quiescence and controls thrombus formation.
AB  - Essentials Nitric oxide synthesis controls protein disulfide isomerase (PDI)
      function. Nitric oxide (NO) modulation of PDI controls endothelial
      thrombogenicity. S-nitrosylated PDI inhibits platelet function and thrombosis.
      Nitric oxide maintains vascular quiescence in part through inhibition of PDI.
      SUMMARY: Background Protein disulfide isomerase (PDI) plays an essential role in
      thrombus formation, and PDI inhibition is being evaluated clinically as a novel
      anticoagulant strategy. However, little is known about the regulation of PDI in
      the vasculature. Thiols within the catalytic motif of PDI are essential for its
      role in thrombosis. These same thiols bind nitric oxide (NO), which is a potent
      regulator of vessel function. To determine whether regulation of PDI represents a
      mechanism by which NO controls vascular quiescence, we evaluated the effect of NO
      on PDI function in endothelial cells and platelets, and thrombus formation in
      vivo. Aim To assess the effect of S-nitrosylation on the regulation of PDI and
      other thiol isomerases in the vasculature. Methods and results The role of
      endogenous NO in PDI activity was evaluated by incubating endothelium with an NO
      scavenger, which resulted in exposure of free thiols, increased thiol isomerase
      activity, and enhanced thrombin generation on the cell membrane. Conversely,
      exposure of endothelium to NO+ carriers or elevation of endogenous NO levels by
      induction of NO synthesis resulted in S-nitrosylation of PDI and decreased
      surface thiol reductase activity. S-nitrosylation of platelet PDI inhibited its
      reductase activity, and S-nitrosylated PDI interfered with platelet aggregation,
      alpha-granule release, and thrombin generation on platelets. S-nitrosylated PDI
      also blocked laser-induced thrombus formation when infused into mice. S
      nitrosylated ERp5 and ERp57 were found to have similar inhibitory activity.
      Conclusions These studies identify NO as a critical regulator of vascular PDI,
      and show that regulation of PDI function is an important mechanism by which NO
      maintains vascular quiescence.

PMID- 30207067
TI  - Association between the T6459C point mutation of the mitochondrial MT-CO1 gene
      and susceptibility to sepsis among Chinese Han people.
AB  - To search for an association between sepsis and mitochondrial genetic basis, we
      began our study. In this study, a proband harbouring mitochondrial T6459C
      mutation with sepsis and his Chinese Han pedigree including 7 members of 3
      generations were enrolled. General information, blood parameters and
      mitochondrial full sequence scanning of all members were performed, and cellular
      functions, including cellular reactive oxygen species (ROS) levels, mitochondrial
      membrane potential (MMP), degrees of cell apoptosis and adenosine triphosphate
      (ATP) concentrations, were measured in members with and without the T6459C
      mutation. Through mitochondrial full sequence scanning and analysis of all
      members we found, the maternal members (I-1, II-1, II-2 and II-4) in this Chinese
      Han pedigree all had the mitochondrial T6459C mutation and were used as the
      mutation group. The non-maternal members (II-3, III-1 and III-2) did not have
      this mutation and were used as the non-mutation group. The differences in all
      indicators, including the blood routine, blood biochemistry and coagulation
      function tests, between members in these two groups were not significant. Under
      the non-stimulation condition, the mutation group had higher ROS levels (4210.42
      +/- 1043.35 vs 3387.78 +/- 489.66, P = .028) and apoptosis ratios (P = .004) and
      lower ATP concentrations (P = .049) and MMP levels (P = .047) than the non
      mutation group. After 6 hours of simulated LPS stimulation, the mutation group
      had significantly increased ROS levels (5759.25 +/- 2297.90 vs 3862.00 +/-
      1519.77, P = .045) compared with the non-mutation group, whereas the mutation
      group continued to demonstrate higher ROS levels (P = .045) and apoptosis ratios
      (P = .003) and lower MMP levels (P = .005) and ATP concentrations (P = .010). We
      speculated that the mtDNA T6459C mutation might be the basis for the genetic
      susceptibility to sepsis.

PMID- 30207068
TI  - Targeted metagenomics demonstrates the ecological role of IS1071 in bacterial
      community adaptation to pesticide degradation.
AB  - IS1071, an insertion element that primarily flanks organic xenobiotic degradation
      genes in cultured isolates, is suggested to play a key role in the formation and
      distribution of bacterial catabolic pathway gene clusters. However, in
      environmental settings, the identity of the IS1071 genetic cargo and its
      correspondence to the local selective conditions remain unknown. To respond, we
      developed a long-range PCR approach amplifying accessory genes between two IS1071
      copies from community DNA followed by amplicon sequencing. We applied this method
      to pesticide-exposed environments, i.e. linuron-treated agricultural soil and on
      farm biopurification systems (BPS) treating complex agricultural wastewater, as
      to non-treated controls. Amplicons were mainly recovered from the pesticide
      exposed environments and the BPS matrix showed a higher size diversity compared
      to the agricultural soil. Retrieved gene functions mirrored the main selection
      pressure as (i) a large fraction of the BPS amplicons contained a high variety of
      genes/gene clusters related to the degradation of organics including herbicides
      present in the wastewater and (ii) in the agricultural soil, recovered genes were
      associated with linuron degradation. Our metagenomic analysis extends
      observations from cultured isolates and provides evidence that IS1071 is a
      carrier of catabolic genes in xenobiotica stressed environments and contributes
      to community level adaptation towards pesticide biodegradation.

PMID- 30207069
TI  - Impact of corneal disease from patients' and ophthalmologists' perspectives.

PMID- 30207071
TI  - Clinical reasoning model for pharmacy students.
AB  - BACKGROUND: Clinical reasoning is an essential health care professional skill.
      Typically, pharmacy students figure out how to reason clinically on their own
      through the observation of skilled clinicians in various patient care settings.
      The need to start developing clinical reasoning skills in the pre-clinical years
      has increased interest in classroom-based clinical reasoning instruction.
      CONTEXT: The focus of the current clinical reasoning literature is on teaching
      and assessing medical student clinical reasoning skills. Some literature is
      available for other health care professions, but there is little information
      regarding pharmacy student clinical reasoning skills. The current accreditation
      standards for pharmacy education in the USA require the assessment of clinical
      reasoning skills, but do not provide guidance regarding content, depth or breadth
      of skill development. INNOVATION: A 2-credit pharmacy elective clinical reasoning
      course and a new integrated clinical reasoning model were developed for first-,
      second- and third-year pre-clinical Doctor of Pharmacy students. The new
      integrated clinical reasoning model, designed to guide pharmacy students through
      the clinical reasoning processes for making patient-specific therapeutic
      recommendations, integrates standard Subjective-Objective-Assessment-Planning
      (SOAPing) processes with pharmacy-specific elements of clinical reasoning.
      IMPLICATIONS: Student achievement on whole case-based exams, designed to assess
      clinical reasoning skills, and student satisfaction with the course were high;
      however, longitudinal experience with cohorts internal and external to this
      institution is necessary to determine whether this type of course and clinical
      reasoning model is scalable, and whether the model has a measurable impact on
      student performance in the clinical year of the curriculum.

PMID- 30207070
TI  - Paraneoplastic hypereosinophilic syndrome associated with IL3-IgH positive acute
      lymphoblastic leukemia.

PMID- 30207072
TI  - "A change in perspective": Exploring the experiences of adolescents with
      hereditary tumor predisposition.
AB  - BACKGROUND: Hereditary tumor predisposition syndromes (HTPSs) are being
      recognized more frequently in the etiology of pediatric cancer. Previous research
      indicates that disclosure of tumor susceptibility is a significant event in
      adolescents' lives. Insight into adolescents' adjustment to knowledge of their
      syndromes can guide healthcare delivery, particularly genetic counseling. This
      study explored the experiences of adolescents with hereditary tumor
      predisposition and their perceptions of living at risk. METHODS: Seven
      adolescents, ages 14 to 17, representing six different childhood-onset HTPSs,
      were purposively sampled and interviewed using a study-specific semistructured
      interview guide. We explored the disclosure process, support systems, and the
      perceived benefits and harms of knowledge of hereditary tumor susceptibility.
      Interview transcripts were analyzed via interpretive description. RESULTS: Three
      major themes emerged from the data: (1) The benefits of knowledge outweigh the
      harms; (2) context surrounding genetic testing must be recognized; and (3) self
      concept is influenced but not defined by tumor risk. CONCLUSIONS: We conclude
      that adolescents recognize the challenges associated with awareness of tumor
      predisposition but may also identify positive aspects in their experiences,
      reflecting a changed life perspective. Results of this exploratory study suggest
      strategies that can guide pretest and posttest genetic counseling of adolescents
      for HTPSs, facilitating the adaptive incorporation of genetic information into an
      adolescent's self-concept.

PMID- 30207073
TI  - Quality of life and participation of young adults with a visual impairment aged
      18-25 years: comparison with population norms.
AB  - PURPOSE: To compare health-related quality of life and participation of visually
      impaired young adults with normative groups, and to explore severity of vision
      loss and its association with participation and quality of life. METHODS: Young
      adults aged 18-25 years (n = 172) registered at two Dutch low vision
      rehabilitation organizations completed the Short Form Health Survey (SF-36),
      EuroQol-5 Dimensions (EQ-5D), Impact on Participation and Autonomy (IPA) and Low
      Vision Quality of Life questionnaire (LVQOL). EQ-5D and SF-36 scores were
      compared to age-specific norms. IPA scores were compared to norms of a population
      having three chronic diseases simultaneously. Linear regression was used to
      assess the association between severity of vision loss (mild VI, moderate VI and
      severe VI/blindness), and quality of life and participation. RESULTS:
      Participants scored significantly worse on almost all (sub)scales compared with
      relevant norms. Effect sizes for the EQ-5D and SF-36 (sub)scales were mostly
      small; moderate and large effect sizes were found for the IPA. Compared to young
      adults with mild VI, corrected models showed a significant association between
      having moderate VI and the physical component score of the SF-36, and between
      severe VI/blindness and the LVQOL. CONCLUSION: VI has a moderate impact on some
      aspects of quality of life and a large impact on participation of young adults
      when compared with relevant normative populations. Severity of vision loss is
      associated with worse physical functioning and vision-related quality of life.
      The results contribute to a better understanding of the impact of VI and might
      lead to improved low vision services.

PMID- 30207074
TI  - 5-HT2 and 5-HT2B antagonists attenuate pro-fibrotic phenotype in human adult
      dermal fibroblasts by blocking TGF-beta1 induced non-canonical signaling pathways
      including STAT3.
AB  - BACKGROUND: Release of 5-hydroxytryptamine (5-HT; serotonin) from activated
      platelets following microvascular injury leads to tissue fibrosis. 5-HT strongly
      induces extracellular matrix synthesis in dermal fibroblasts in a transforming
      growth factor beta 1 (TGF-beta1)-dependent manner. AIM: To evaluate anti-fibrotic
      properties of inhibitors of 5-HT2 and 5-HT2B (terguride, SB204741) respectively
      in human adult dermal fibroblasts (HADF) derived from a patient with scleroderma.
      METHODS: Anti-fibrotic efficacy of 5-HT2 and 5-HT2B inhibitors was evaluated as
      per two strategies: HADF were incubated with 5-HT (1 MUM)/TGF-beta1 (10 ng/mL)
      for 1 hour followed by 5-HT (1 MUM)/TGF-beta1 (10 ng/mL) and terguride or
      SB204741 (1 MUM, each) for 24 hours (post-treatment strategy) and HADF were
      treated with terguride or SB204741 (1 MUM, each) for 1 hour followed by 5-HT (1
      MUM)/TGF-beta1 (10 ng/mL) for 24 hours (pre-treatment strategy). Real time
      quantitative polymerase chain reaction for expression of pro-fibrotic (TGFBeta1,
      COL1A1, COL1A2, ACTA2, CTGF and FN1) and anti-fibrotic genes (MMP2/TIMP1) was
      performed. Expression of type I collagen, alpha smooth muscle actin (alpha-SMA),
      phosphorylation of Smad3, ERK1/2 and STAT3 was examined by immunoblotting.
      RESULTS: Stimulation of HADF cells with 5-HT/TGF-beta1 led to the increased
      expression of pro-fibrotic genes which was significantly reduced by both
      terguride and SB204741. Expression of anti-fibrotic genes was not affected upon
      incubation with the inhibitors. In 5-HT-stimulated HADF, treatment with terguride
      and SB204741 decreased type I collagen and alpha-SMA. In 5-HT/TGF-beta1
      stimulated HADF, terguride and SB204741 treatment reduced ERK1/2 and STAT3
      phosphorylation but did not influence Smad3 phosphorylation. CONCLUSION:
      Terguride and SB204741 reduce pro-fibrotic potential of HADF cells and suppress
      TGF-beta1-mediated non-canonical pathways, ERK1/2 and STAT3 which have been
      implicated in the regulation of pro-fibrotic genes and in the development of
      fibrosis. Taken together, our data suggest that 5-HT inhibitors might reduce
      fibrosis via suppression of TGF-beta1-mediated non-canonical signaling pathways.
      These observations have important therapeutic implications for fibrotic
      disorders.

PMID- 30207075
TI  - Estimating heritability of refractive error in Koreans: the Korea National Health
      and Nutrition Examination Survey.
AB  - PURPOSE: To estimate the familial correlation and heritability of refractive
      error in general Korean population. METHODS: From the Korea National Health and
      Nutrition Examination Survey, 13 258 subjects of 7920 families, who were aged
      >=19 years, were included in the study. Using variance components analysis, the
      additive genetic effect, or heritability, and the common and unique environmental
      effects on refractive error were examined, adopting common environments shared by
      cohabiting family or by siblings. RESULTS: The proportions of hyperopia, myopia
      and high myopia in Koreans were 0.8%, 45.2% and 5.7% respectively. The
      correlation coefficients of spherical equivalent (SE) were 0.257 for parent
      offspring pairs, 0.410 for sibling pairs and 0.112 for spouse pairs (p < 0.001
      for all). Common environment shared by siblings affected the variation of SE
      significantly (p < 0.001), but that shared by cohabitants did not (p = 0.395).
      Adopting common environment shared by siblings, the heritability, common
      environmental effect and unique environmental effect of refractive error were
      42.1 +/- 3.3%, 11.8 +/- 3.5% and 46.1 +/- 3.9% respectively. Heritabilities of
      hyperopia, myopia and high myopia were 45.7%, 44.3% and 68.9% respectively.
      Adjusted odds ratios of myopia among offspring were 3.78 given one parent has
      myopia and 4.43 when both parents have myopia. CONCLUSION: Refractive error is
      influenced by common environment shared by siblings. The heritability of
      refractive error is higher for high myopia than for myopia or hyperopia.

PMID- 30207077
TI  - Continuous Virus Inactivation: How to Generate a Plug Flow.
AB  - To realize continuous integrated manufacturing of biopharmaceuticals, all steps
      of production have to be operated in a continuous mode. Virus inactivation is a
      crucial step in this process, and due to standard procedures and a fixed
      residence time, it is particularly challenging to realize. Two articles in this
      issue present possible solutions to this problem.

PMID- 30207076
TI  - Risk-based breast cancer follow-up stratified by age.
AB  - Although personalization of cancer care is recommended, current follow-up after
      the curative treatment of breast cancer is consensus-based and not differentiated
      for base-line risk. Every patient receives annual follow-up for 5 years without
      taking into account the individual risk of recurrence. The aim of this study was
      to introduce personalized follow-up schemes by stratifying for age. Using data
      from the Netherlands Cancer Registry of 37 230 patients with early breast cancer
      between 2003 and 2006, the risk of recurrence was determined for four age groups
      (<50, 50-59, 60-69, >70). Follow-up was modeled with a discrete-time partially
      observable Markov decision process. The decision to test for recurrences was made
      two times per year. Recurrences could be detected by mammography as well as by
      self-detection. For all age groups, it was optimal to have more intensive follow
      up around the peak in recurrence risk in the second year after diagnosis. For the
      first age group (<50) with the highest risk, a slightly more intensive follow-up
      with one extra visit was proposed compared to the current guideline
      recommendation. The other age groups were recommended less visits: four for ages
      50-59, three for 60-69, and three for >=70. With this model for risk-based follow
      up, clinicians can make informed decisions and focus resources on patients with
      higher risk, while avoiding unnecessary and potentially harmful follow-up visits
      for women with very low risks. The model can easily be extended to take into
      account more risk factors and provide even more personalized follow-up schedules.

PMID- 30207078
TI  - Toxoplasmosis and secondary Guillain-Barre associated with ruxolitinib as graft
      versus-host disease treatment.

PMID- 30207079
TI  - Exercise and glucose control in children with insulin resistance: prevalence of
      non-responders.
AB  - BACKGROUND: Exercise training improves cardiometabolic outcomes in 'mean terms',
      but little information is available in children about the impact of the
      frequency/week and the wide inter-individual variability to exercise training
      reported in adults. OBJECTIVES: We compared the effects of resistance training
      (RT) and high-intensity interval training (HIT), and 'high' and 'low' frequency
      of training/week, for their effectiveness in decreasing insulin resistance (IR)
      levels in schoolchildren. A second aim was to decscribe and compare the
      prevalence of non-responders (NRs) between the different frequencies of training
      protocol. METHODS: Fifty-three schoolchildren with IR were randomly assigned into
      four groups: RT at high frequency (three times/week), HIT at high frequency, RT
      at a low frequency (two times/week) and HIT at low frequency. The intervention
      lasted 6 weeks. Blood samples and body composition, blood pressure and
      performance measurements were taken before and after the intervention. RESULTS:
      The prevalence of NRs was similar between the RTHF and HITHF (25.0% vs. 25.0%, P
      > 0.05) and RTLF and HITLF groups (20.0% vs. 46.6%, P = 0.174) for decreasing
      homeostasis model assessment of IR. However, significant differences in the
      prevalence of NRs were detected between RTHF and HITHF groups in fasting glucose
      (FGL) (18.7% vs. 58.3%, P < 0.031). CONCLUSIONS: Both RT and HIT improves the
      glucose control parameters in schoolchildren over 6 weeks, but only HIT is
      independent of a high or low frequency of training/week. The prevalence of NRs is
      similar for decreasing homeostasis model assessment of IR comparing each exercise
      mode in high vs. low frequency/week. However, both high- and low-frequency RT and
      HIT results in differences in the prevalence of NRs for FGL and other
      cardiometabolic and performance outcomes.

PMID- 30207080
TI  - BMI trajectories and risk of overall and grade-specific prostate cancer: An
      observational cohort study among men seen for prostatic conditions.
AB  - BACKGROUND: Dynamic longitudinal patterns in body mass index (BMI) have been
      suggested to better predict health outcomes than static measures. Effects of BMI
      trajectories on prostate cancer (PCa) risk have not been thoroughly explored.
      METHODS: Cohort data were derived from electronic medical records of patients who
      were admitted to a tertiary-care hospital in the Southeastern USA during 1994
      2016. Patients with a history of urologic clinic visit because of any prostatic
      condition and with repeatedly measured BMI (n = 4857) were included. BMI
      trajectories prior to PCa diagnosis were assessed using the developmental
      trajectory analysis method. Cox proportional hazards regression modeling was used
      to estimate adjusted hazard ratio (aHR) with 95% confidence intervals (CIs) for
      overall and grade-specific PCa. RESULTS: The median age (interquartile range,
      IQR) of the participants at baseline was 63 (54, 72) years. Over a median follow
      up (IQR) of 8.0 (2.0, 13.0) years, 714 (14.7%, 714/4857) were diagnosed with PCa.
      Men with growing BMI trajectory progressing from normal weight to
      overweight/obese had a 76% increased PCa risk (aHR = 1.76; 95% CI: 1.25, 2.48),
      and men being obese and experiencing progressive weight gain had 3.72-fold
      increased PCa risk (aHR = 3.72; 95% CI: 1.60, 8.66), compared to men with
      persistently normal BMI. The associations were more pronounced for PCa with
      Gleason score >=7. No significant association of decreasing BMI trajectory
      progressing from obese to normal BMI was found with PCa risk. CONCLUSIONS:
      Progressively body weight gain during middle-to-late adulthood was associated
      with increased PCa risk for both normal weight and overweight men. Further
      studies are warranted to confirm this finding.

PMID- 30207081
TI  - Molecular survey of HEV infection in wild boar population in Italy.
AB  - Hepatitis E virus (HEV) is an RNA virus causing an acute generally self-limited
      disease in humans. An increasing number of autochthonous cases linked to zoonotic
      transmission of HEV genotype 3 have been reported over the last 10 years in
      Europe. Pigs and wild boars are considered the main reservoirs. The principal
      route of transmission in Europe is food-borne, linked by direct or indirect
      evidence to the consumption of raw or undercooked pork products and wild boar
      meat. In this study, we sampled 92 wild boar (Sus scrofa) livers during active
      surveillance in five municipalities in Central Italy throughout the hunting
      season 2016-2017. HEV RNA was detected in 52.2% of liver sampled with prevalence
      ranging from 0.0% to 65.7%. HEV-positive wild boars were detected in all but one
      area of hunting. Phylogenetic analysis showed that strains clustered within the
      two subtypes HEV-3c and HEV-3f and displayed a wide range of phylogenetic
      diversity. Several strains were circulating in the areas investigated; animals
      possibly belonging to the same family group hunted by the same team were infected
      with a unique strain (100% nucleotide identity). As wild animals are a proven
      source of HEV transmission to humans and pigs, the high prevalence observed (mean
      52.2%) poses a question on the risk of consuming raw or undercooked wild boar
      meat, and thus, this subject deserves further investigations.

PMID- 30207082
TI  - Association of sperm source with miscarriage and take-home baby after ICSI in
      cryptozoospermia: a meta-analysis of testicular and ejaculated sperm.
AB  - BACKGROUND: Miscarriage and take-home baby are the most important issues to
      patients with cryptozoospermia in receiving intracytoplasmic sperm injection
      (ICSI). The ICSI usually use ejaculated or testicular sperm. Unfortunately, no
      synthesized evidence reported miscarriage and take-home baby rate between the two
      sperm sources. OBJECTIVES: This study aimed to compare the miscarriage and take
      home baby rate of ICSI using testicular and ejaculated sperm in patient with
      cryptozoospermia. MATERIALS AND METHODS: We conducted meta-analyses that were
      based on data from Cochrane library, Ovid, PubMed, ScienceDirect, Scopus, and Web
      of Science. The pooled analyses used risk ratio (RR) in random-effects model.
      Sensitivity analyses by subgrouping were completed to explore the associations
      between mean age and outcome. RESULTS: This study identified 331 potential
      citations and included four cohort studies for qualitative and quantitative
      synthesis. The four studies involved 331 patients with 479 ICSI cycles. The
      results showed no significant difference in miscarriage between testicular sperm
      group and ejaculated sperm group (RR = 1.06, 95% CI 0.48-2.35, p = 0.88). Yet,
      take-home babies per embryo transfer in testicular sperm group (53/226, 23.45%)
      was more than ejaculated sperm group (59/429, 13.75%) (RR = 1.72, 95% CI 1.21
      2.44, p = 0.002). Similar results can be found in take-home babies per ICSI cycle
      (RR = 1.77, 95% CI 1.28-2.44, p = 0.0005), especially in younger couple (RR =
      1.93, 95% CI 1.11-3.34, p = 0.02). No small study bias was detected in the
      analyses. DISCUSSION: This study found that testicular sperm has more advantage
      for ICSI in patients with cryptozoospermia, especially in younger couple. These
      findings may help guide us when deciding the optimal method of sperm harvest for
      men with cryptozoospermia. CONCLUSION: Comparing to ejaculated sperm, testicular
      sperm showed benefits for take-home baby rate, but not for miscarriage in
      patients with cryptozoospermia.

PMID- 30207083
TI  - Analysis of Codman microcerebrospinal fluid shunt.
AB  - INTRODUCTION: Ventriculo-peritoneal cerebrospinal fluid (CSF) shunt is the most
      common method of treating pediatric hydrocephalus. The Codman microadjustable
      valve (CMAV) is a CSF shunt constructed for children. The objective of the study
      was (a) to analyze complications after insertion of a CMAV shunt in hydrocephalic
      children, (b) to analyze complications after replacing a CMAV by an adult-type
      Codman Hakim adjustable valve shunt (CHAV), and to (c) analyze the in vitro
      characteristics of the CMAV shunt and correlate the findings with the clinical
      performance of the shunt. METHODS: A retrospective study analyzed a cohort of
      hydrocephalic children who had received a CMAV shunt and later replaced by a CHAV
      shunt. We report on the complications that resulted from replacing the CMAV with
      the CHAV. We tested six CMAV shunts with or without an antisiphon device (ASD) in
      which opening pressure, resistance, sensitivity to abdominal pressure, ASD
      position dependency, and function were determined. The test results were
      correlated with the clinical performance of the shunt in the retrospective study.
      RESULTS: Thirty-seven children (19 boys, 18 girls) were identified. Within the
      first month after shunt placement, a total of 10 patients (27%) developed
      complications including infections, hygromas, and shunt dysfunction. Shunt
      survival varied from 1 week to 145 months. Over the 10-year follow-up period, 13
      children had their shunts replaced, six of them with a CHAV without any further
      complications. A bench test of the CMAV was done to test whether the opening
      pressure was in agreement with the manufacturer's specifications. Our results
      were generally in agreement with specifications stated by the manufacturer.
      CONCLUSION: Replacing a CMAV with a CHAV was well tolerated by the patients.
      Bench test results were generally in agreement with manufacturers specifications.
      Replacing a CMAV with a CHAV in pediatric hydrocephalus patients can be
      accomplished safely.

PMID- 30207084
TI  - Risk factors of lymph node metastasis in 734 early gastric carcinoma radical
      resections in a Chinese population.
AB  - OBJECTIVE: To investigate the risk factors of lymph node metastasis (LNM) in
      early gastric carcinoma (EGC) in a Chinese population. METHODS: The data were
      analyzed to determine risk factors of LNM. The patients' characteristics, the
      tumor's location, gross features, histological type, differentiation, invasive
      depth, lymphovascular invasion (LVI), perineural invasion and the numbers of
      lymph nodes retrieved and involved were statistically analyzed. RESULTS: A total
      of 734 patients with EGC were finally enrolled in the study, and LNM was present
      in 14.2% (104/734) of them. By univariate analysis, significant risk factors for
      LNM included depressed or excavated gross patterns, size >=1.0 cm, SM2,
      moderate/poor differentiation, histological type of hepatoid or micropapillary
      adenocarcinoma, LVI, perineural invasion and tumor necrosis. By multivariate
      analysis, independent risk factors for LNM were size >=3.0 cm (odds ratio [OR]
      4.9), SM2 (OR 2.4), moderate (OR 3.6) and poor (OR 5.0) differentiation, LVI (OR
      3.1) and tumor necrosis (OR 1.7). Early gastric cardiac carcinoma (OR 0.3) had a
      significantly lower risk than non-cardiac carcinoma. No LNM was identified in 67
      EGC of <1.0 cm in size and without poor differentiation, in 142 intramucosal EGC
      cases of smaller than 2.0 cm and without poor differentiation, in 129 cases of
      well-differentiated EGC without deep SM2 submucosal invasion, or in 54
      intramucosal EGC located in the gastric cardia. CONCLUSION: Independent risk
      factors for LNM in EGC include tumor size >=3.0 cm, SM2 invasion, moderate/poor
      differentiation, LVI and tumor necrosis. Early cardiac carcinoma had a
      significantly lower risk of LNM than non-cardiac EGC.

PMID- 30207085
TI  - Characterization of long-term outcomes for pediatric patients with epithelioid
      hemangioma.
AB  - Epithelioid hemangioma (EH) is a rare benign vascular tumor that occurs in soft
      tissues and bone and presents between the third and sixth decades of life. Little
      is known about the clinical course and outcomes of pediatric EH. We report 11
      patients diagnosed with EH at a median age of 14.4 years. One patient treated
      with interferon and one with sirolimus exhibited partial response for >2 years.
      Although a benign neoplasm, EH is difficult to manage without standard protocols
      and portends considerable morbidity. Our findings suggest medical management,
      particularly sirolimus, may benefit these patients; however, long-term follow-up
      is needed.

PMID- 30207086
TI  - Rhodium-Catalyzed Domino Hydroformylation/Double-Cyclization Reaction of
      Arylacetylenecarboxamides: Diastereoselectivity Studies and Application in the
      Synthesis of 1-Azabicyclo[x.y.0]alkanes.
AB  - A domino method for the rapid syntheses of 1-azabicyclo[x.y.0]alkane scaffolds,
      such as indolizidines, quinolizidines, decahydropyridoazepines, and their
      derivatives, has been developed. This strategy involved a rhodium-catalyzed
      hydroformylation of allyl-, 3-butenyl-, or homoallyl amides, followed by two
      spontaneous ring closures under mild conditions. The reaction scope and
      diastereoselectivity were fully explored by changing the substitution pattern on
      the amide and by altering the length of the carbon chain. This method was applied
      to the syntheses of natural alkaloids tashiromine and epilupinine. The clear
      differences between the reactivities of two isomeric amide substrates, 3
      butenamide 1 j and homoallyl amide 1 i, could be attributed to better HOMO-LUMO
      overlap in the transition states that were derived from butenamides during
      cyclization. This explanation was supported by DFT calculations.

PMID- 30207088
TI  - ColXalpha1 is a stromal component that colocalizes with elastin in the breast
      tumor extracellular matrix.
AB  - The tumor microenvironment regulates tissue development and homeostasis, and its
      dysregulation contributes to neoplastic progression. Increased expression of type
      X collagen alpha-1 (ColXalpha1) in tumor-associated stroma correlates with poor
      pathologic response to neoadjuvant chemotherapy in estrogen receptor (ER) and
      human epidermal growth factor receptor 2 (HER2)-positive breast cancers.
      Evaluation of ColXalpha1 expression patterns suggests a potential connection with
      elastin fibers. To investigate the possible interaction between ColXalpha1 and
      elastin, we evaluated the expression of ColXalpha1 in relation to elastin fibers
      in normal breast tissue, ductal carcinoma in situ, and invasive breast carcinomas
      at cellular and subcellular levels. Our findings demonstrate that ColXalpha1
      colocalizes with elastin in invasive breast cancer-associated stroma by
      immunohistochemistry, immunofluorescence, and electron microscopy. In 212
      invasive breast carcinomas, this complex was aberrantly and selectively expressed
      in tumor extracellular matrix in 79% of ER+/HER2-, 80% of ER+/HER2+, 76% of ER
      /HER2+, and 58% of triple negative breast cancers. In contrast, ColXalpha1 was
      generally absent, while elastin was present perivascularly in normal breast
      tissue. ColXalpha1 and elastin were coexpressed in 58% of ductal carcinoma in
      situ (DCIS) in periductal areas. In mass-forming DCIS with desmoplastic stroma,
      the complex was intensely expressed in periductal areas as well as within the
      tumor-associated stroma in all cases. Our data suggest that the breast carcinoma
      neoplastic process may involve aberrant expression of ColXalpha1 and elastin in
      the tumor microenvironment emerging early at the DCIS stage. Enrichment of these
      complexes in tumor-associated stroma may represent a stromal signature indicative
      of intrinsic differences between breast cancers. These findings shed light on
      investigation into the role of aberrant collagen complex expression in
      tumorigenesis and tumor progression which may be leveraged in therapeutic and
      theranostic applications.

PMID- 30207090
TI  - Analytical quantification, intoxication case series, and pharmacological
      mechanism of action for N-ethylnorpentylone (N-ethylpentylone or ephylone).
AB  - Synthetic cathinones continue to proliferate in clandestine drug markets
      worldwide. N-ethylnorpentylone (also known as N-ethylpentylone or ephylone) is a
      popular emergent cathinone, yet little information is available about its
      toxicology and pharmacology. Here we characterize the analytical quantification,
      clinical presentation, and pharmacological mechanism of action for N
      ethylnorpentylone. Liquid chromatography coupled to tandem mass spectrometry (LC
      MS/MS) was used to quantify N-ethylnorpentylone in blood obtained from human
      cases. Clinical features exhibited by the intoxicated individuals are described.
      The activity of N-ethylnorpentylone at plasma membrane transporters for dopamine
      (DAT), norepinephrine (NET) and 5-HT (SERT) was assessed using in vitro assays
      measuring uptake inhibition and evoked release of [3 H] neurotransmitters in rat
      brain synaptosomes. Our LC-MS/MS method assayed N-ethylnorpentylone
      concentrations with limits of detection and quantification of 1 and 5 ng/mL,
      respectively. Quantitation was linear from 5 to 500 ng/mL, and the method
      displayed specificity and reproducibility. Circulating concentrations of N
      ethylnorpentylone ranged from 7 to 170 ng/mL in clinical cases, and the
      associated symptoms included palpitations, tachycardia, agitation,
      hallucinations, coma and death. N-Ethylnorpentylone was a potent inhibitor at DAT
      (IC50  = 37 nM), NET (IC50  = 105 nM) and SERT (IC50  = 383 nM) but displayed no
      transporter releasing activity. We present a validated method for quantifying N
      ethylnorpentylone in human case work. The drug is a psychomotor stimulant capable
      of inducing serious cardiovascular and neurological side-effects which can be
      fatal. In vitro findings indicate that N-ethylnorpentylone exerts its effects by
      potent blockade of DAT and NET, thereby elevating extracellular levels of
      dopamine and norepinephrine in the brain and periphery.

PMID- 30207087
TI  - Angiotensin-converting enzyme 2 deficiency accelerates and angiotensin 1-7
      restores age-related muscle weakness in mice.
AB  - BACKGROUND: A pharmacologic strategy for age-related muscle weakness is desired
      to improve mortality and disability in the elderly. Angiotensin-converting enzyme
      2 (ACE2) cleaves angiotensin II into angiotensin 1-7, a peptide known to protect
      against acute and chronic skeletal muscle injury in rodents. Since physiological
      aging induces muscle weakness via mechanisms distinct from other muscle
      disorders, the role of ACE2-angiotensin 1-7 in age-related muscle weakness
      remains undetermined. Here, we investigated whether deletion of ACE2 alters the
      development of muscle weakness by aging and whether angiotensin 1-7 reverses
      muscle weakness in older mice. METHODS: After periodic measurement of grip
      strength and running distance in male ACE2KO and wild-type mice until 24 months
      of age, we infused angiotensin 1-7 or vehicle for 4 weeks, and measured grip
      strength, and excised tissues. Tissues were also excised from younger (3-month
      old) and middle-aged (15-month-old) mice. Microarray analysis of RNA was
      performed using tibialis anterior (TA) muscles from middle-aged mice, and some
      genes were further tested using RT-PCR. RESULTS: Grip strength of ACE2KO mice was
      reduced at 6 months and was persistently lower than that of wild-type mice (p <
      0.01 at 6, 12, 18, and 24-month-old). Running distance of ACE2KO mice was shorter
      than that of wild-type mice only at 24 months of age [371 +/- 26 vs. 479 +/- 24
      (m), p < 0.01]. Angiotensin 1-7 improved grip strength in both types of older
      mice, with larger effects observed in ACE2KO mice (% increase, 3.8 +/- 1.5 and
      13.3 +/- 3.1 in wild type and ACE2KO mice, respectively). Older, but not middle
      aged ACE2KO mice had higher oxygen consumption assessed by a metabolic cage than
      age-matched wild-type mice. Angiotensin 1-7 infusion modestly increased oxygen
      consumption in older mice. There was no difference in a wheel-running activity or
      glucose tolerance between ACE2KO and wild-type mice and between mice with vehicle
      and angiotensin 1-7 infusion. Analysis of TA muscles revealed that p16INK4a, a
      senescence-associated gene, and central nuclei of myofibers increased in middle
      aged, but not younger ACE2KO mice. p16INK4a and central nuclei increased in TA
      muscles of older wild-type mice, but the differences between ACE2KO and wild-type
      mice remained significant (p < 0.01). Angiotensin 1-7 did not alter the
      expression of p16INK4a or central nuclei in TA muscles of both types of mice.
      Muscle ACE2 expression of wild-type mice was the lowest at middle age (2.6 times
      lower than younger age, p < 0.05). CONCLUSIONS: Deletion of ACE2 induced the
      early manifestation of muscle weakness with signatures of muscle senescence.
      Angiotensin 1-7 improved muscle function in older mice, supporting future
      application of the peptide or its analogues in the treatment of muscle weakness
      in the elderly population.

PMID- 30207089
TI  - Ligand-Controlled Assembly of Heteropolyoxomolybdates from Plenary Keggin
      Germanomolybdates and Cu-Ln Heterometallic Units.
AB  - By virtue of combining an in-situ assembly process with a stepwise synthesis in
      conventional aqueous solution, two series of unique organic-inorganic hybrid
      heteropolyoxomolybdates were constructed from plenary Keggin germanomolybdates
      and Cu-Ln heterometallic units and fully characterized: [H2 INA]2 H8 [LnCu(INA)4
      (H2 O)6 ]2 [alpha-GeMo12 O40 ]3 ?52 H2 O (Ln=La3+ (1), Ce3+ (2), Pr3+ (3), Nd3+
      (4), Sm3+ (5), Eu3+ (6); HINA=isonicotinic acid) and (NH4 )[Cu(PA)2 ][Cu(PA)2
      Ln(H2 O)8 ][alpha-GeMo12 O40 ]?10 H2 O (Ln=Nd3+ (7), Sm3+ (8), Eu3+ (9);
      HPA=picolinic acid). The most remarkable structural characteristic of compounds 1
      6 was that their molecular units were defined by three discrete plenary Keggin
      [alpha-GeMo12 O40 ]4- polyoxoanions and two organic-inorganic hybrid
      heterometallic [LnCu(INA)4 (H2 O)6 ]+ moieties, whereas compounds 7-9 exhibited a
      nice-looking 1D chain-like structure that was built from plenary [alpha-GeMo12
      O40 ]4- polyoxoanions, pendent [Cu(PA)2 ] complexes, and bridging {[Cu(PA)2
      ][Ln(H2 O)8 ]}3+ heterometallic groups. Notably, two different pyridine
      carboxylic acid ligands led to the discrepancy between the two structure types.
      To the best of our knowledge, compounds 1-9 constitute the first examples of
      plenary Keggin heterometallic germanomolybdates that include Cu-Ln-organic
      subunits. Further studies revealed that compounds 3 and 8 exhibited fast
      adsorption capacity for cationic dyes methylene blue (MB) and rhodamine B (RhB)
      in water. Moreover, compounds 3 and 8 could quickly and selectively adsorb MB
      from a mixture of MB/methyl orange (MO) or MB/azophloxine (Apo).

PMID- 30207091
TI  - Molybdenum-Based Co-catalysts in Photocatalytic Hydrogen Production: Categories,
      Structures, and Roles.
AB  - Photocatalytic hydrogen production by using solar energy has attracted great
      interest around the world. The main challenges are the high costs of the
      photocatalysts and the low efficiency of photocatalytic hydrogen production. Co
      catalysts, as crucial components of photocatalysts, are usually used to stimulate
      photoexcited electron transfer from the light absorber to the surface, and they
      also catalyze the proton-reduction reaction to form H2 in water. However, most co
      catalysts used in photocatalytic hydrogen production are noble metals, which are
      expensive and contradict the low-costs demanded by industry. Therefore, the
      development of earth-abundant and cheap co-catalysts to replace noble metals is
      necessary for photocatalytic H2 production. This account highlights the
      performance and roles of molybdenum-based non-noble metal co-catalysts in
      photocatalytic hydrogen production. We developed a series of inexpensive and
      efficient molybdenum-based co-catalysts. We demonstrated that more H2 could be
      produced by loading Mo-based co-catalysts on CdS by using the co-precipitation
      method than by using traditional Pt/CdS same under the same photocatalytic
      conditions. The molybdenum-based co-catalysts were able to form heterojunctions,
      which served as bridges to facilitate the transport and separation of
      photogenerated charges; moreover, the molybdenum-based co-catalysts were able to
      accept and store photoexcited electrons owing to their large specific
      capacitance. The stored photoelectrons could then be released according to proton
      reduction processes to form H2 . Furthermore, the molybdenum-based co-catalysts
      were found to have metastable state structures and multiple valence states, which
      provided more active sites and effectively catalyzed the production of H2 and
      inhibited the reverse reaction. The discovery of Mo-based co-catalysts with
      superior properties will provide guidance for the design of new co-catalysts.

PMID- 30207092
TI  - Impact of beta blockers on survival outcomes in ovarian cancer: a nationwide
      population-based cohort study.
AB  - OBJECTIVE: The impact of beta blockers (BBs) on survival outcomes in ovarian
      cancer was investigated. METHODS: By using Korean National Health Insurance
      Service Data, Cox proportional hazards regression was performed to analyze hazard
      ratios (HRs) with 95% confidence intervals (CIs) adjusting for confounding
      factors. RESULTS: Among 866 eligible patients, 206 (23.8%) were BB users and 660
      (76.2%) were non-users. Among the 206 BB users, 151 (73.3%) were non-selective
      beta blocker (NSBB) users and 105 (51.0%) were selective beta blocker (SBB)
      users. BB use in patients aged >=60 years, longer duration use (>=1 year), in
      patients with Charlson Comorbidity Index (CCI) >=3, and in cardiovascular disease
      including hypertension was associated with better survival outcome. These
      findings were observed in both NSBB and SBB. When duration of medication was
      analyzed based on number of days, NSBB (>=180 days) was associated with improved
      overall survival (OS) with a relatively shorter period of use compared to SBB
      (>=720 days). In multivariate Cox proportional hazards model, longer duration of
      BB medication (>=1 year) was an independent favorable prognostic factor for both
      OS and disease-specific survival in ovarian cancer patients. CONCLUSION: In our
      nationwide population-based cohort study, BB use was associated with better
      survival outcomes in ovarian cancer in cases of long term duration of use, in
      older patients, and in cardiovascular and/or other underlying disease (CCI >=3).

PMID- 30207094
TI  - Trachelectomy for stage IB1 cervical cancer with tumor size >2 cm: trends and
      characteristics in the United States.

PMID- 30207093
TI  - Quality indicators for cervical cancer care in Japan.
AB  - OBJECTIVE: We aimed to propose a set of quality indicators (QIs) based on the
      clinical guidelines for cervical cancer treatment published by The Japan Society
      of Gynecologic Oncology, and to assess adherence to standard-of-care as an index
      of the quality of care for cervical cancer in Japan. METHODS: A panel of clinical
      experts devised the QIs using a modified Delphi method. Adherence to each QI was
      evaluated using data from a hospital-based cancer registry of patients diagnosed
      in 2013, and linked with insurance claims data, between October 1, 2012, and
      December 31, 2014. All patients who received first-line treatment at the
      participating facility were included. The QI scores were communicated to
      participating hospitals, and additional data about the reasons for non-adherence
      were collected. RESULTS: In total, 297 hospitals participated, and the care
      provided to 15,163 cervical cancer patients was examined using 10 measurable QIs.
      The adherence rate ranged from 50.0% for 'cystoscope or proctoscope for stage
      IVA' to 98.8% for 'chemotherapy using platinum for stage IVB'. Despite the
      variation in care, hospitals reported clinically valid reasons for more than half
      of the non-adherent cases. Clinically valid reasons accounted for 75%, 90.9%,
      73.4%, 44.5%, and 88.1% of presented non-adherent cases respectively. CONCLUSION:
      Our study revealed variations in pattern of care as well as an adherence to
      standards-of-care across Japan. Further assessment of the causes of variation and
      non-adherence can help identify areas where improvements are needed in patient
      care.

PMID- 30207095
TI  - Robotic lower pelvic port placement for optimal upper paraaortic lymph node
      dissection.
AB  - OBJECTIVE: Upper paraaortic lymph node dissection (UPALD) to the infrarenal level
      is one of the most challenging robotic procedures. Because robotic system has the
      limitation in robotic arm mobility. This surgical video introduces a novel
      robotic approach, lower pelvic port placement (LP3), to perform optimally and
      simultaneously both UPALD and pelvic procedures in gynecologic cancer patients
      using da Vinci Xi system. METHODS: The patient presented with high-grade
      endometrial cancer. She underwent robotic surgical staging operation. For the
      setup of the LP3, a line was drown between both anterior superior iliac spines.
      At 3 cm below this line, another line was drown and four robotic ports were
      placed on this line. RESULTS: After paraaortic lymph node dissection (PALD) was
      completed, the boom of robotic system was rotated 180 degrees  to retarget for
      the pelvic lateral displacement. Robotic ports were placed and docked again. The
      operation was completed robotically without any complication. CONCLUSION: The LP3
      was feasible for performing simultaneously optimal PALD as well as procedures in
      pelvic cavity in gynecologic cancer patients. The advantage of LP3 technique is
      the robotic port placement that affords for multi-quadrant surgery, abdominal and
      pelvic dissection. The LP3 is facilitated by utilizing advanced technology of Xi
      system, including the patient clearance function, the rotating boom, and 'port
      hopping' that allows using every ports for a camera. The LP3 will enable surgeons
      to extend the surgical indication of robotic surgical system in the gynecologic
      oncologic field.

PMID- 30207096
TI  - Clinical utility of CA-125 in the management of uterine carcinosarcoma.

PMID- 30207097
TI  - Treatment results of the second-line chemotherapy regimen for patients with low
      risk gestational trophoblastic neoplasia treated with 5-day methotrexate and 5
      day etoposide.
AB  - OBJECTIVE: Highly effective chemotherapy for patients with low-risk gestational
      trophoblastic neoplasia (GTN) is associated with almost a 100% cure rate.
      However, 20%-30% of patients treated with chemotherapy need to change their
      regimens due to severe adverse events (SAEs) or drug resistance. We examined the
      treatment outcomes of second-line chemotherapy for patients with low-risk GTN.
      METHODS: Between 1980 and 2015, 281 patients with low-risk GTN were treated. Of
      these 281 patients, 178 patients were primarily treated with 5-day intramuscular
      methotrexate (MTX; n=114) or 5-day drip infusion etoposide (ETP; n=64). We
      examined the remission rates, the drug change rates, and the outcomes of second
      line chemotherapy. RESULTS: The primary remission rates and drug resistant rates
      of 5-day ETP were significantly higher (p<0.001) and significantly lower
      (p=0.002) than those of 5-day MTX, respectively. Forty-seven patients (26.4%)
      required a change in their chemotherapy regimen due to the SAEs (n=16) and drug
      resistance (n=31), respectively. Of these 47 patients failed the first-line
      regimen, 39 patients (39/47, 82.9%) were re-treated with single-agent
      chemotherapy, and 35 patients (35/39, 89.7%) achieved remission. Four patients
      failed second-line, single-agent chemotherapy and eight patients (17.0%) who
      failed first-line regimens were treated with combined or multi-agent chemotherapy
      and achieved remission. CONCLUSIONS: Patients with low-risk GTN were usually
      treated with single-agent chemotherapy, while 20%-30% patients had to change
      their chemotherapy regimen due to SAEs or drug resistance. The second-line
      regimens of single-agent chemotherapy were effective; however, there were several
      patients who needed multiple agents and combined chemotherapy to achieve
      remission.

PMID- 30207098
TI  - BRCA1/2 mutations, including large genomic rearrangements, among unselected
      ovarian cancer patients in Korea.
AB  - OBJECTIVE: We performed small-scale mutation and large genomic rearrangement
      (LGR) analysis of BRCA1/2 in ovarian cancer patients to determine the prevalence
      and the characteristics of the mutations. METHODS: All ovarian cancer patients
      who visited a single institution between September 2015 and April 2017 were
      included. Sanger sequencing, multiplex ligation-dependent probe amplification
      (MLPA), and long-range polymerase chain reaction (PCR) were performed to
      comprehensively study BRCA1/2. The genetic risk models BRCAPRO, Myriad, and
      BOADICEA were used to evaluate the mutation analysis. RESULTS: In total, 131
      patients were enrolled. Of the 131 patients, Sanger sequencing identified 16
      different BRCA1/2 small-scale mutations in 20 patients (15.3%). Two novel
      nonsense mutations were detected in 2 patients with a serous borderline tumor and
      a large-cell neuroendocrine carcinoma. MLPA analysis of BRCA1/2 in Sanger
      negative patients revealed 2 LGRs. The LGRs accounted for 14.3% of all identified
      BRCA1 mutations, and the prevalence of LGRs identified in this study was 1.8% in
      111 Sanger-negative patients. The genetic risk models showed statistically
      significant differences between mutation carriers and non-carriers. The 2
      patients with LGRs had at least one blood relative with breast or ovarian cancer.
      CONCLUSION: Twenty-two (16.8%) of the unselected ovarian cancer patients had
      BRCA1/2 mutations that were detected through comprehensive BRCA1/2 genetic
      testing. Ovarian cancer patients with Sanger-negative results should be
      considered for LGR detection if they have one blood relative with breast or
      ovarian cancer. The detection of more BRCA1/2 mutations in patients is important
      for efforts to provide targeted therapy to ovarian cancer patients.

PMID- 30207099
TI  - Association of tumor differentiation grade and survival of women with squamous
      cell carcinoma of the uterine cervix.
AB  - OBJECTIVE: To examine the association between tumor grade and survival for women
      with squamous cervical cancer. METHODS: This retrospective observational study
      utilized the Surveillance, Epidemiology, and End Result program data between 1983
      and 2013 to examine women with squamous cervical cancer with known tumor
      differentiation grade. Multivariable analyses were performed to assess
      independent associations between tumor differentiation grade and survival.
      RESULTS: A total of 31,536 women were identified including 15,175 (48.1%) with
      grade 3 tumors, 14,084 (44.7%) with grade 2 neoplasms and 2,277 (7.2%) with grade
      1 tumors. Higher tumor grade was significantly associated with older age, higher
      stage disease, larger tumor size, and lymph node metastasis (all, p<0.001). In a
      multivariable analysis, grade 2 tumors (adjusted-hazard ratio [HR]=1.21; p<0.001)
      and grade 3 tumors (adjusted-HR=1.45; p<0.001) were independently associated with
      decreased cause-specific survival (CSS) compared to grade 1 tumors. Among the
      7,429 women with stage II-III disease who received radiotherapy without surgical
      treatment, grade 3 tumors were independently associated with decreased CSS
      compared to grade 2 tumors (adjusted-HR=1.16; p<0.001). Among 4,045 women with
      node-negative stage I disease and tumor size <=4 cm who underwent surgical
      treatment without radiotherapy, grade 2 tumors (adjusted-HR=2.54; p=0.028) and
      grade 3 tumors (adjusted-HR=4.48; p<0.001) were independently associated with
      decreased CSS compared to grade 1 tumors. CONCLUSION: Our study suggests that
      tumor differentiation grade may be a prognostic factor in women with squamous
      cervical cancer, particularly in early-stage disease. Higher tumor grade was
      associated with poorer survival.

PMID- 30207100
TI  - Effect of the pulmonary recruitment maneuver on pain after laparoscopic
      gynecological oncologic surgery: a prospective randomized trial.
AB  - OBJECTIVE: To evaluate the effectiveness of the pulmonary recruitment maneuver
      (PRM) at the end of the operation to decrease laparoscopy-induced abdominal or
      shoulder pain after gynecological oncologic surgery. METHODS: In total, 113 women
      undergoing laparoscopic surgery for malignant or premalignant gynecological
      lesions were assigned randomly to two groups: the PRM group (the patient was
      placed in the Trendelenburg position (30 degrees ) and the PRM, consisting of two
      manual pulmonary inflations to a maximum pressure of 40 cmH2O) (n=54) and the
      control group (n=52). Postoperative shoulder and abdominal pain was assessed 12,
      24, and 48 hours later using a visual analog scale (0-10). In addition, the
      incidence of post-discharge nausea and vomiting was recorded until 48 hours after
      discharge. RESULTS: Postoperative shoulder pain at 12 and 24 hours was
      significantly less severe in the PRM group (2.2+/-0.5 and 2.0+/-0.4) than in the
      control group (4.0+/-0.5 and 3.9+/-0.4; both p<0.001). The PRM significantly
      reduced the severity of upper abdominal pain at 12 and 24 h compared with the
      control group (3.1+/-0.4 and 2.9+/-0.4 vs. 5.9+/-0.5 and 4.9+/-0.5; both
      p<0.001). The analgesic requirement during the postoperative period was similar
      in the two groups (control group, 78.8%; PRM group, 75.9%; p=0.719). CONCLUSION:
      The PRM effectively and safely reduced postoperative shoulder and upper abdominal
      pain levels in patients undergoing laparoscopic gynecological oncologic surgery.
      Trial registry at ClinicalTrials.gov, NCT01940042.

PMID- 30207101
TI  - Checkpoint-inhibition in ovarian cancer: rising star or just a dream?
AB  - The introduction of checkpoint inhibitors revolutionized immuno-oncology. The
      efficacy of traditional immunotherapeutics, like vaccines and immunostimulants
      was very limited due to persistent immune-escape strategies of cancer cells.
      Checkpoint inhibitors target these escape mechanisms and re-direct the immune
      system to anti-tumor toxicity. Phenomenal results have been reported in entities
      like melanoma, where no other therapy was able to demonstrate survival benefit,
      before the introduction of immunotherapeutics. The first experience in ovarian
      cancer (OC) was reported for nivolumab, a fully human anti-programmed cell death
      protein 1 (PD1) antibody, in 2015. While the data are extraordinary for a mono
      immunotherapeutic agent and very promising, they do not match up to the
      revolutionary results in entities like melanoma. The key to exceptional treatment
      response in OC, could be the identification of the most immunogenic patients. We
      hypothyse that BRCA mutation could be a predictor of improved response in OC. The
      underlying DNA-repair-deficiancy should result in increased immunogenicity
      because of higher mutational load and more neoantigen presentation. This
      hypothesis was not tested to date and should be subject to future trials. The
      present article gives an overview of the immunologic background of checkpoint
      inhibition (CI). It presents current data on nivolumab and other checkpoint
      inhibitors in solid tumors and OC specifically and depicts important topics in
      the management of this novel substance group, such as side effect control,
      diagnostic PD-1/programmed cell death-ligand 1 (PD-L1) expression assessment and
      management of pseudoprogression.

PMID- 30207102
TI  - Current landscape and future perspective of sentinel node mapping in endometrial
      cancer.
AB  - Endometrial cancer (EC) represents the most common gynecological neoplasm in
      developed countries. Surgery is the mainstay of treatment for EC. Although EC is
      characterized by a high prevalence several features regarding its management are
      still unclear. In particular the execution of lymphadenectomy is controversial.
      The recent introduction of sentinel node mapping represents the mid-way between
      the execution and omission of node dissection in EC patients. In the present
      review we discuss the emerging role of sentinel node mapping in EC. In addition,
      we discussed how type of tracers utilized and site of injection impacted on
      sentinel node detection rates. Future perspective regarding EC management are
      also discussed.

PMID- 30207103
TI  - LncRNA XLOC_006390 facilitates cervical cancer tumorigenesis and metastasis as a
      ceRNA against miR-331-3p and miR-338-3p.
AB  - OBJECTIVE: Cervical cancer is one of the most common malignant tumors. Our
      previous results showed that long non-coding RNA (lncRNA) XLOC_006390 plays an
      important role in cervical cancer. In this study, we have explored the mechanism
      of action of lncRNA XLOC_006390. METHODS: LncRNA XLOC_006390 was proposed to
      exercise its function as a competing endogenous RNA (ceRNA), and its potential
      targeted miRNAs was predicted through the database LncBase Predicted v.2. Two
      miRNAs, miR-331-3p, and miR-338-3p, were chosen for the study. Expression of
      miRNAs and lncRNA in cervical cancer cells and tissues was detected by reverse
      transcription polymerase chain reaction. To determine the correlation, silencing
      of XLOC_006390, over-expression of miR-331-3p, and miR-338-3p was performed in
      SiHa and Caski cell lines, respectively. RESULTS: Based on the interactive effect
      between miRNA and lncRNA, miR-331-3p and miR-338-3p were significantly
      downregulated in cervical cancer cells and tissues, and their expression levels
      were negatively related to that of lncRNA. Our results also showed that the
      expression of miR-331-3p target gene NRP2, miR-338-3p target genes PKM2, EYA2 was
      significantly downregulated when the XLOC_006390 was knocked down. Further,
      XLOC_006390 was found to facilitate cervical cancer tumorigenesis and metastasis
      by downregulating miR-331-3p and miR-338-3p expression. CONCLUSION: Taken
      together, our study demonstrated that XLOC_006390 may serve as a ceRNA and
      reversely regulates the expression of miR-331-3p and miR-338-3p, thus
      facilitating cervical cancer tumorigenesis and metastasis.

PMID- 30207104
TI  - Weekly versus 3-weekly paclitaxel in combination with carboplatin in advanced
      ovarian cancer: which is the optimal adjuvant chemotherapy regimen?
AB  - The 3-weekly regimen of carboplatin and paclitaxel is the backbone of first line
      adjuvant chemotherapy for advanced ovarian cancer. The landmark Japanese
      Gynaecologic Oncology Group (JGOG) 3016 study demonstrated significant
      improvements in progression-free survival and overall survival with dose dense
      weekly administration of paclitaxel in combination with 3-weekly carboplatin.
      However, efforts to replicate these benefits have failed in subsequent phase III
      trials. Weekly paclitaxel is purported to have enhanced antitumor activity, with
      stronger anti-angiogenic effects, and yet is better tolerated. In this review, we
      explore the rationale for dose dense weekly paclitaxel, and compare the relevant
      trials as well as quality of life considerations. Possible reasons for the
      difference in outcomes between the JGOG 3016 and other studies are reviewed, with
      a focus on how the addition of bevacizumab, the variations between histological
      and molecular subtypes of epithelial ovarian cancers, and ethnic pharmacogenetic
      differences may potentially affect the efficacy of dose dense paclitaxel.

PMID- 30207105
TI  - Postoperative chemoradiotherapy versus radiotherapy alone for elderly cervical
      cancer patients with positive margins, lymph nodes, or parametrial invasion.
AB  - OBJECTIVE: Women with cervical cancer (CC) found to have positive surgical
      margins, positive lymph nodes, and/or parametrial invasion receive a survival
      benefit from postoperative chemoradiotherapy (CRT) vs. radiation therapy (RT)
      alone. However, older women may not benefit to the same extent, as they are at
      increased risk of death from non-oncologic causes as well as toxicities from
      oncologic treatments. This study sought to evaluate whether there was a survival
      benefit of CRT over RT in elderly patients with cervical cancer. METHODS: The
      National Cancer Database was queried for patients >=70 years old with newly
      diagnosed IA2, IB, or IIA CC and positive margins, parametrial invasion, and/or
      positive nodes on surgical resection. Statistics included logistic regression,
      Kaplan-Meier overall survival (OS), and Cox proportional hazards modeling
      analyses. RESULTS: Altogether, 166 patients met inclusion criteria; 62 (37%)
      underwent postoperative RT and 104 (63%) underwent postoperative CRT. Younger
      patients and those living in areas of higher income were less likely to receive
      CRT, while parametrial invasion and nodal involvement were associated with an
      increased likelihood (p<0.05 for all). There were no OS differences by treatment
      type. Subgroup analysis by number of risk factors, as well as each of the 3 risk
      factors separately, also did not reveal any OS differences between cohorts.
      CONCLUSION: In the largest such study to date, older women with postoperative
      risk factor(s) receiving RT alone experienced similar survival as those
      undergoing CRT. Although causation is not implied, careful patient selection is
      paramount to balance treatment-related toxicity risks with theoretical outcome
      benefits.

PMID- 30207106
TI  - Performance of pre-treatment 18F-fluorodeoxyglucose positron emission
      tomography/computed tomography for detecting metastasis in ovarian cancer: a
      systematic review and meta-analysis.
AB  - OBJECTIVE: We describe a systematic review and meta-analysis of the performance
      of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed
      tomography (PET/CT) for detecting metastasis in ovarian cancer. METHODS: MEDLINE
      and Embase were searched for diagnostic accuracy studies that used 18F-FDG PET or
      PET/CT for pre-treatment staging, using surgical findings as the reference
      standard. Sensitivities and specificities were pooled and plotted in a hierarchic
      summary receiver operating characteristic plot. Potential causes of heterogeneity
      were explored through sensitivity analyses. RESULTS: Eight studies with 594
      patients were included. The overall pooled sensitivity and specificity for
      metastasis were 0.72 (95% confidence interval [CI]=0.61-0.81) and 0.93 (95%
      CI=0.85-0.97), respectively. There was considerable heterogeneity in sensitivity
      (I2=97.57%) and specificity (I2=96.74%). In sensitivity analyses, studies that
      used laparotomy as the reference standard showed significantly higher sensitivity
      and specificity (0.77; 95% CI=0.67-0.87 and 0.96; 95% CI=0.92-0.99, respectively)
      than those including diagnostic laparoscopy (0.62; 95% CI=0.46-0.77 and 0.84; 95%
      CI=0.69-0.99, respectively). Higher specificity was shown in studies that
      confirmed surgical findings by pathologic evaluation (0.95; 95% CI=0.90-0.99)
      than in a study without pathologic confirmation (0.69; 95% CI=0.24-1.00). Studies
      with a lower prevalence of the FDG-avid subtype showed higher specificity (0.97;
      95% CI=0.94-1.00) than those with a greater prevalence (0.89; 95% CI=0.80-0.97).
      CONCLUSION: Pre-treatment 18F-FDG PET/CT shows moderate sensitivity and high
      specificity for detecting metastasis in ovarian cancer. With its low false
      positive rate, it can help select surgical approaches or alternative treatment
      options.

PMID- 30207109
TI  - ASGO 5th International Workshop on Gynecologic Oncology.

PMID- 30207107
TI  - Upregulation of long non-coding RNA XIST has anticancer effects on epithelial
      ovarian cancer cells through inverse downregulation of hsa-miR-214-3p.
AB  - OBJECTIVE: The present study is to evaluate the biological functions of long non
      coding RNA (lncRNA), X-inactive specific transcript, X-inactive specific
      transcript (XIST) in human epithelial ovarian cancer (EOC). METHODS: XIST was
      upregulated in EOC cell lines, CAOV3 and OVCAR3 cells by lentiviral transduction.
      The effects of XIST overexpression on cancer cell proliferation, invasion,
      chemosensitivity and in vivo tumor growth were investigated, respectively.
      Possible sponging interaction between XIST and human microRNA hsa-miR-214-3p was
      further evaluated. Furthermore, hsa-miR-214-3p was overexpressed in XIST
      upregulated CAOV3 and OVCAR3 cells to evaluate its effect on XIST-mediated EOC
      regulation. RESULTS: Lentivirus-mediated XIST upregulation had significant
      anticancer effects in CAOV3 and OVCAR3 cells by suppressing cancer cell
      proliferation, invasion, increasing cisplatin chemosensitivity and inhibiting in
      vivo tumor growth. Hsa-miR-214-3p was confirmed to directly bind XIST, and
      inversely downregulated in XIST-upregulated EOC cells. In EOC cells with XIST
      upregulation, secondary lentiviral transduction successfully upregulated hsa-miR
      214-3p expression. Subsequently, hsa-miR-214-3p upregulation functionally
      reversed the anticancer effects of XIST-upregulation in EOC. CONCLUSION:
      Upregulation of lncRNA XIST may suppress EOC development, possibly through
      sponging effect to induce hsa-miR-214-3p downregulation.

PMID- 30207110
TI  - Aortic Valve Prolapse and Aortic Regurgitation During Long-Term Follow Up in
      Children with Ventricular Septal Defect.
AB  - BACKGROUND: Aortic valve prolapse (AVP) and aortic regurgitation (AR) can develop
      in a subset of patients with ventricular septal defect (VSD). The incidence and
      progression of AVP and AR with VSD at long-term follow up was evaluated. METHODS:
      The records of 2,275 patients with isolated VSD who had been diagnosed using
      echocardiography at the present authors' institution between 1988 and 2014 were
      reviewed. RESULTS: AVP was detected in 178 patients (7.8%), using
      echocardiography. Of 178 patients with AVP, AR was detected in 124 (AR incidence
      5.4%). A total of 142 patients was followed medically during a median of 10 years
      after AVP had appeared. Initially, no AR was noted in 66 of these patients,
      trivial AR in 41, mild AR in 30, moderate in three, and severe in two. Trivial AR
      developed in 20 and mild in eight of 66 patients who had no AR. In 18 of 61
      patients (29.5%), trivial AR progressed to mild during a median of 3.6 years, and
      in five of 18 patients (27.7%) mild AR progressed to moderate during a median of
      2.3 years. Postoperatively, AR improved in 17 patients, remained unchanged in 12,
      and worsened in four at between two months and 16.5 years of follow up (median
      6.6 years). CONCLUSIONS: Frequent (six-month) echocardiographic evaluation in
      patients with perimembraneous or muscular outlet VSD after AVP and AR development
      may be useful. In addition, surgical intervention in patients with
      perimembraneous or muscular outlet VSD, AVP and mild AR may prevent the worsening
      of AR.

PMID- 30207108
TI  - Survival in clinical stage I endometrial cancer with single vs. multiple positive
      pelvic nodes: results of a multi-institutional Italian study.
AB  - OBJECTIVE: To investigate survival outcomes in endometrioid endometrial cancer
      (EEC) patients with single vs. multiple positive pelvic lymph nodes. METHODS: We
      performed a retrospective evaluation of all consecutive patients with
      histologically proven International Federation of Gynecology and Obstetrics
      (FIGO) stage IIIC1 EEC who underwent primary surgical treatment between 2004 and
      2014 at seven Italian gynecologic oncology referral centers. Patients with pre-
      or intra-operative evidence of extra-uterine disease (including the presence of
      bulky nodes) and patients with stage IIIC2 disease were excluded, in order to
      obtain a homogeneous population. RESULTS: Overall 140 patients met the inclusion
      criteria. The presence of >1 metastatic pelvic node was significantly associated
      with an increased risk of recurrence and mortality, compared to only 1 metastatic
      node, at both univariate (recurrence: hazard ratio [HR]=2.19; 95% confidence
      interval [CI]=1.2-3.99; p=0.01; mortality: HR=2.8; 95% CI=1.24-6.29; p=0.01) and
      multivariable analysis (recurrence: HR=1.91; 95% CI=1.02-3.56; p=0.04; mortality:
      HR=2.62; 95% CI=1.13-6.05; p=0.02) and it was the only independent predictor of
      prognosis in this subset of patients. Disease-free survival (DFS) and disease
      specific survival (DSS) were significantly longer in patients with only 1
      metastatic node compared to those with more than 1 metastatic node (p=0.008 and
      0.009, respectively). CONCLUSION: The presence of multiple metastatic nodes in
      stage IIIC1 EEC represents an independent predictor of worse survival, compared
      to only one positive node. Our data suggest that EEC patients may be categorized
      according to the number of positive nodes.

PMID- 30207111
TI  - Electrocardiographic Correlates of Myocardial Injury After Transcatheter Aortic
      Valve Replacement.
AB  - BACKGROUND: Transcatheter aortic valve replacement (TAVR) is associated with
      several conduction abnormalities and a need for pacemaker placement. The study
      aim was to describe all electrocardiographic (ECG) changes seen after TAVR, to
      compare such changes between transapical (TA) and transfemoral (TF) patient
      cohorts, and to assess their impact on postoperative outcomes. METHODS: Between
      March 2009 and July 2014, a total of 286 consecutive patients underwent TAVR at
      the present authors' institution. Perioperative data were collected
      prospectively, while preoperative and predischarge electrocardiograms were
      reviewed retrospectively by an independent cardiologist. RESULTS: A greater
      proportion of TA patients experienced ECG changes than TF patients at the time of
      discharge (78% versus 42%; p <0.0001), with more intraventricular conduction
      abnormalities (29% versus 15%; p = 0.006), and a trend towards more frequent
      atrioventricular block and pacemaker placement. Troponin levels were higher in
      patients with new ECG changes (4.61ng/ml versus 2.12 ng/ml; p = 0.0009). New
      intraventricular conduction abnormalities were associated with increased one-year
      mortality only in the TF subgroup (65% versus 84%; p = 0.028). Six TA patients
      demonstrated new ECG findings of myocardial infarction, and this was associated
      with greater 30-day mortality (67% versus 98%; p = 0.012), although none met the
      clinical criteria for myocardial infarction. CONCLUSIONS: New ECG changes after
      TAVR, including new conduction abnormalities, were seen more frequently in TA
      patients. When seen in TF patients, they were associated with decreased survival.
      ECG findings of new myocardial infarction, seen only in TA patients, were also
      associated with decreased survival.

PMID- 30207112
TI  - Valve-Sparing Aortic Root Repair Compared to Composite Aortic Root Replacement: A
      Systematic Review and Meta-Analysis.
AB  - BACKGROUND: Aortic root aneurysms represent a significant risk of morbidity and
      mortality. Composite root replacement is the preferred practice for repair,
      although recently valve-sparing replacement has become a popular alternative. The
      study aim was to identify comparative studies that simultaneously analyzed
      composite root and valve-sparing root replacement outcomes. METHODS: A systematic
      review of the current literature was performed through four major databases, from
      inception until 2016. All comparative studies of valve-sparing versus composite
      root replacement were identified. All studies were assessed by two reviewers for
      their applicability and inclusion. RESULTS: A total of 12 comparative papers was
      identified encompassing 2,352 patients (700 valve-sparing and 1,652 composite);
      the mean follow up was 3.7 +/- 1.7 years. Aortic cross-clamp and cardiopulmonary
      bypass times were lower in the composite group (p <0.0001 and p<0.00001,
      respectively). In-hospital mortality was low, but higher in the composite group
      (p = 0.002). Only one study reported long-term follow up. In studies reporting
      reoperation, there was slight difference favoring composite over valve-sparing
      replacement (p = 0.05). CONCLUSIONS: Valve-sparing and composite root replacement
      remain feasible options for replacement of the aortic root. Long-term data of
      comparative studies are not yet available to assess the viability of these
      procedures.

PMID- 30207113
TI  - Long-Term Results after Modified Bentall Operation in 200 Patients.
AB  - BACKGROUND: Composite graft replacement of the aortic root is the treatment of
      choice for an array of aortic root pathologies, such as annuloaortic ectasia,
      Marfan syndrome and acute or chronic aortic dissection type A. In this
      retrospective study of the authors' aortic surgery database, an exploration was
      made of factors related to early and long-term morbidity and mortality of
      patients who underwent this procedure. METHODS: Between 2000 and 2009, a total of
      200 consecutive patients (male:female ratio 4:1; mean age 56.2 +/- 11.66 years)
      underwent the modified Bentall operation at the authors' institution, with a
      composite graft (mechanical valve) being used to correct aortic root pathology.
      All preoperative, perioperative and postoperative data, as well as long-term
      follow up data, were retrieved from the authors' aortic surgery database.
      RESULTS: Preoperative characteristics of the patients included elective and
      emergency operations (83.1% and 15.9%, respectively). Intraoperative and 30-day
      mortalities were 2% and 3.5%, respectively, while the rate of postoperative
      cerebrovascular events was 1.5%. Long-term survival at a mean follow up of 110
      months for the elective and emergency groups was 88.6% and 71.9%, respectively (p
      = 0.007). Moreover, during the same period new cerebrovascular events were
      observed in 5.8% of cases. Predictive factors for late survival were type of
      surgery (elective versus emergency; p = 0.023), conduit size (<=23 mm versus >23
      mm; p = 0.053) , age >65 years (p = 0.001), intensive care unit stay (days; p
      <0.001) and postoperative creatinine level (p = 0.002). Survival rates at one,
      three, five and 10 years postoperatively were 93.5%, 92.5%, 91.5% and 85.9%,
      respectively. CONCLUSIONS: Patients who underwent the modified Bentall operation
      presented with minimal major adverse effects and demonstrated a good long-term
      survival.

PMID- 30207114
TI  - Cardioembolic Stroke from an Atrial Myxoma in a Pediatric Patient: A Case Report
      and Review of the Literature.
AB  - Cardioembolic stroke is an uncommon phenomenon in pediatric patients. Although
      the heart is the usual source of the condition, cardiac myxomas are still
      considered to be a rare cause in children. The case is presented of a 13-year
      old, right-handed Saudi boy who showed right-sided weakness for 30 h prior to
      hospital admission that involved the face, arm, and leg, with slurred speech. The
      patient had been discharged previously from a local hospital, without active
      management. An examination showed decreased strength on the right side, with
      hyperreflexia and an up-going plantar response. The work-up included magnetic
      resonance imaging, which demonstrated multiple bilateral acute infarcts involving
      mainly the left cerebellum and a small focus in the right cerebellum.
      Transthoracic echocardiography demonstrated a left atrial mass measuring 1.9 cm *
      2.4 cm, attached to the septum. The mass was resected after anticoagulation, and
      histopathology confirmed a benign myxoma. This case of cardioembolic stroke was
      the first to be identified in a pediatric patient in Saudi Arabia, and may easily
      have been missed. Brain imaging and echocardiography should be performed as soon
      as possible in such patients in order to guide patient management.

PMID- 30207115
TI  - Survival Advantage of MitraClip(r) Over Medical Treatment in Patients with Mitral
      Regurgitation: A Meta-Analysis.
AB  - BACKGROUND: The MitraClip(r) system is a percutaneous treatment for mitral
      regurgitation (MR) that has shown promising results in patients who are
      inoperable or at high risk for mitral surgery. Data on the efficacy of the system
      over optimal medical therapy, above all in patients with functional MR, are
      scarce. The study aim was to assess the effect of MitraClip on the survival of
      patients with moderate/severe or severe MR compared to medical therapy, using
      meta-analytical techniques. METHODS: Independently, reviewers searched
      electronically for relevant articles based on predefined criteria and end-points.
      Only articles with a comparison between MitraClip and conservative therapy were
      included. Standard meta-analysis techniques were used. The primary outcomes were
      30-day and one-year mortalities. RESULTS: Five observational reports were
      included that enrolled a total of 1,271 patients: 720 patients underwent
      percutaneous mitral valve repair (PMVR) with the MitraClip device, and 551 were
      managed conservatively. A total of 49 all-cause mortality events was reported at
      30 days: 3.05% (22/720) in the PMVR arm, and 4.90% (27/510) in the conservative
      group, with no significant differences in all-cause mortality (OR 0.64; 95% CI
      0.36-1.14). A total of 269 all-cause mortality events at one year was reported:
      15.14% (109/720) in the PMVR arm, and 29.04% (160/551) in the conservative group.
      A significant difference favoring PMVR with the MitraClip system over medical
      therapy alone was observed (OR 0.44; 95% CI 0.30-0.64, p <0.0001). Neither
      significance between study heterogeneity (p = 0.18) nor publication bias was
      detected (p = 0.3). CONCLUSIONS: PMVR with the MitraClip system may be associated
      with an improvement in one-year survival compared to stand-alone medical
      management.

PMID- 30207116
TI  - Long-Term Follow Up After Successful Percutaneous Balloon Mitral Valvuloplasty.
AB  - BACKGROUND: Percutaneous balloon mitral valvuloplasty (PMV) is the cornerstone of
      rheumatic mitral stenosis treatment in suitable patients. Previous studies have
      reported low rates of technical failure and few major complications, with good
      long-term results after successful PMV. The study aim was to assess the very long
      term outcome in patients after PMV performed at a single tertiary center.
      METHODS: Between 1991 and 2010, a total of 213 consecutive patients underwent PMV
      at the authors' center. The criteria used to define successful procedure were
      post-procedural mitral valve area >=1.5 cm2 and mitral regurgitation less than
      grade III, without in-hospital major cardiac or cerebrovascular events. The
      primary endpoint evaluated during the follow up period was the occurrence of
      cardiovascular death and need for mitral reintervention (percutaneous or
      surgical). Kaplan-Meier curves were generated to determine event rates, and
      predictors of major cardiac events in patients with successful PMV were
      determined using Cox regression analysis. RESULTS: A total of 190 patients (89%)
      underwent a successful PMV; 88% of these are currently being followed up at the
      authors' center. During a mean follow up of 11.2 +/- 7.3 years, at least one
      major adverse cardiac event occurred in 25.1% of patients (6.6% all-cause death,
      6.6% repeated PMV, 21% required mitral valve surgery). Cumulative event-free
      survival at 20 years was 54.7 +/- 6.3%. On univariate analysis, the
      echocardiographic score [hazard ratio (HR) = 1.25 (1.00-1.70), p <0.05], left
      atrial diameter [HR = 1.06 (1.01-1.11), p <0.05] and mean mitral valve gradient
      soon after the procedure [HR = 1.25 (1.02-1.55), p <0.05] were predictors of
      events. On multivariate analysis, the echocardiographic mitral valve score before
      PMV was the only independent predictor of primary outcome [HR=1.75 (1.16-2.64),
      p<0.01]. CONCLUSIONS: Up to 20 years after successful PMV, a sizeable proportion
      of patients remained event-free, which confirmed the late efficacy of PMV. Among
      the present patient cohort, echocardiographic score before PMV was the only
      independent predictor of long term events.

PMID- 30207117
TI  - Prevalence and Doppler Echocardiographic Characteristics of Normally Functioning
      Mitral Prostheses with Mean Gradient >=10 mmHg.
AB  - BACKGROUND: The study aim was to determine the prevalence of normally functioning
      mitral prostheses with mean gradient >=10 mmHg, and to identify the
      characteristics and echocardiographic variables that might be useful to
      distinguish normal function from dysfunction. METHODS: A total of 56 consecutive
      patients with a prosthetic mitral valve and mean gradient >=10 mmHg was
      retrospectively identified. Nineteen patients without subsequent imaging
      confirming normal prosthesis function or dysfunction were excluded; hence, 37
      patients were classified as obstruction, insufficiency, or normal prosthesis
      (high-gradient; NPHG). A comparison group of 25 patients with a mean
      transprosthetic gradient of <=5 mmHg (low-gradient group) was also identified.
      RESULTS: Of the 37 patients, seven (19%) had obstruction, 10 (27%) had
      significant valvular or perivalvular insufficiency, and 20 (54%) were deemed
      NPHG. NPHG patients had a similar net atrioventricular compliance (Cn) to those
      with obstruction and insufficiency, which was significantly lower than the low
      gradient group. The cardiac index (CI) was significantly higher in the NPHG group
      (3.4 +/- 0.9 l/min/m2) compared to all other groups (p = 0.001). Receiver
      operator characteristic curves showed that the indexed effective orifice area
      (EOAi), effective orifice area (EOA) and velocity-time integral ratio
      distinguished NPHG from abnormal prosthesis function in patients with mean
      gradients >=10 mmHg (area under curve = 0.92, 0.86, and 0.82, respectively).
      CONCLUSIONS: The study data suggested that a plurality of individuals with a mean
      transprosthetic mitral gradient >=10 mmHg will be found to have a normally
      functioning prosthesis. Most of these patients will have a small EOAi, a reduced
      Cn, and a relatively increased CI.

PMID- 30207118
TI  - Characterization of Effective Orifice Areas of Mitral Prosthetic Heart Valves: An
      In-Vitro Study.
AB  - BACKGROUND: Reference values of hemodynamic parameters for the assessment of
      prosthetic heart valves are necessary, and ideally need to be provided by
      entities independent of the valve manufacturers. Thus, the study aim was to
      provide, in vitro, normal reference values of the effective orifice area (EOA)
      for different models and sizes of mitral prosthetic valve, and to assess the
      determinants of EOA and mean transvalvular pressure gradient (mTPG). METHODS:
      Four models of mechanical prostheses were tested (one mono-leaflet, three bi
      leaflet) and four models of bioprostheses (two bovine pericardial, two porcine)
      on a double-activation pulsed duplicator that was specifically designed and
      optimized for assessing the hemodynamic performance of mitral prosthetic valves.
      The hemodynamic conditions were standardized and included for bioprostheses: two
      mitral flow volumes, three mean aortic pressures, two heart rates, and three E/A
      ratios. The EOAs were measured with Doppler echocardiography, using the same
      method (continuity equation) as was used in the clinical setting. Overestimation
      in term of EOA was defined according to guidelines as >0.25 cm2. RESULTS: EOA
      reference values were recorded. For mono-leaflet prostheses (Medtronic Hall 7700,
      size 25 to 31 mm) 2.29 and 3.49; for bi-leaflet prostheses (St. Jude Medical
      Master and Master HP, sizes 25 to 33 mm and On-X valve, sizes 27-29 mm) 1.34 and
      4.74 cm2; for porcine bioprostheses (Medtronic Mosaic CINCH, sizes 25 to 31 mm
      and St. Jude Epic 100, sizes 25 to 33 mm) 1.35 and 3.56 cm2; for bovine
      pericardial bioprosthetic valves (Edwards Perimount 6900P and Magna Ease 7300,
      sizes 25 to 33 mm) 1.67 and 2.36 cm2. There were some discrepancies between the
      normal reference EOAs measured compared to those provided by the prosthesis
      manufacturers, or in published reports. The bioprosthetic EOAs were shown to be
      smaller than the manufacturers' values in 32% of valves (by an average of 0.57 +/
      0.28 cm2) versus in 7% of valves when compared to values reported elsewhere (by
      an average of 0.43 +/- 0.17 cm2). The relationship between EOA and internal
      orifice area (IOA) varied according to the type of prosthesis. The EOA was close
      to the IOA in mechanical valves (regression slopes 0.87-0.99) but was much
      smaller than the IOA in bioprosthetic valves (slopes 0.25-0.30). The EOA was
      influenced by prosthesis diameter, prosthesis stent diameter and height, while
      the mTPG was influenced by EOA and heart rate. CONCLUSIONS: The present study has
      provided normal reference values of EOAs for several frequently used mitral
      prostheses. This information may be helpful for identifying and quantifying
      prosthetic valve dysfunction and prosthesis-patient mismatch.

PMID- 30207119
TI  - Mitral Valve Repair for Mitral Regurgitation with Congenital Anomalies of the
      Papillary Muscles.
AB  - BACKGROUND: True parachute mitral valve and parachute-like asymmetric mitral
      valve are associated with congenital anomalies of the papillary muscles, which
      involves an abnormal anatomy of the papillary muscles and chordae. METHODS: Two
      patients are described with mitral valve regurgitation and papillary muscle
      anomalies. Mitral valve repair using artificial chordae reconstruction and ring
      annuloplasty was attempted in both cases. RESULTS: The first patient had a true
      parachute mitral valve, while the second patient had a parachute-like asymmetric
      mitral valve. In both patients, widespread leaflet prolapse induced mitral valve
      regurgitation, and the anterior mitral leaflet was thickened because of long-term
      regurgitation. Mitral valve repair using artificial chordae reconstruction and
      ring annuloplasty were successfully performed. At midterm follow up the patients
      did not experience any progression of significant regurgitation or stenosis.
      CONCLUSIONS: Mitral valve repair using artificial chordae reconstruction combined
      with ring annuloplasty is effective for treating regurgitant parachute mitral
      valve in adults.

PMID- 30207120
TI  - Clinicopathological Spectrum of Mitral Valve Myxoma.
AB  - Cardiac myxomas are the most common primary tumors of the heart. Although these
      tumors have been reported in all cardiac chambers, myxomas arising from heart
      valves are extremely rare. Here, the details are described of a patient with
      mitral valve myxoma, and a review is provided of 99 cases reported in the
      literature. Mitral valve myxomas most often occur in middle-aged patients, with a
      slight female predominance. Most of the tumors arise in an isolated fashion on
      the atrial side of the anterior mitral valve leaflet. Embolic events were the
      most frequent manifestation, followed by obstructive symptoms. Unlike atrial wall
      myxomas, these tumors have a lower incidence of constitutional manifestations.
      Tumor resection with valve preservation is the usual method of surgical treatment
      in isolated tumors, while most patients with multiple valve myxomas underwent
      valve replacement. Mitral valve myxomas should be considered in the differential
      diagnosis of mitral valve tumors, with an awareness of a relatively high risk of
      embolic events. This location should not raise suspicion for a heritable myxoma
      syndrome. Prompt surgical resection is warranted to reduce complications.

PMID- 30207121
TI  - Frequency and Clinical Significance of Right Atrial Embryonic Remnants
      Involvement in Infective Endocarditis.
AB  - BACKGROUND: The involvement of atrial embryonic remnants in infective
      endocarditis (IE) has seldom been reported. The study aim was to evaluate the
      prevalence of vegetations on right atrial embryonic remnants (RAER) in patients
      with a definitive diagnosis of IE. METHODS: Since 1998, all consecutive patients
      with suspected IE were referred to the authors' institution to undergo
      transesophageal echocardiography (TEE). Patients with a high probability of IE
      but with a negative result underwent a further TEE examination within 10 days.
      The involvement of RAER was investigated systematically. RESULTS: Among a total
      of 585 patients evaluated, definitive criteria for IE were present in 210
      (35.9%). Right-sided IE was detected in 33 patients (15%); these included 21
      infections on the tricuspid valve (65%), 10 cases of intracardiac electronic
      device infection (29%), one infection on the Thebesian valve (3%), and one on the
      pulmonary valve (3%). The incidence of right-sided IE was 0.84 per 100,000
      population per year. RAER involvement was detected in five patients (15% of right
      sided endocarditis), representing 2.5% of the complete IE series. The incidence
      of RAER endocarditis was 0.13 new cases per 100,000 population per year. The
      Eustachian and Thebesian valves were involved in four cases. Two patients
      presented with pulmonary embolism and died in hospital. Transthoracic
      echocardiography (TTE) allowed the detection of RAER vegetations in two cases.
      CONCLUSIONS: Although the prevalence of embryonic remnants involvement in IE is
      underestimated, it may carry an important embolic risk if undetected. As TTE
      demonstrated only a low sensitivity in the diagnosis of embryonic remnant
      involvement, TEE should be performed systematically and RAER involvement
      carefully sought. TEE is recommended in all patients with a high clinical
      suspicion of right-sided IE. Video 1: Mid-esophageal TEE view. Multiple
      vegetations attached onto the pacemaker leads (broken arrow) and on the
      Eustachian valve (solid arrow). Video 2: Mid-esophageal TEE view. A vegetation
      attached onto the tricuspid valve (broken arrow) and on the Eustachian valve
      (solid arrow).

PMID- 30207122
TI  - Antiplatelet Therapy for Long-Term Management of Patients with Mechanical Aortic
      Prostheses.
AB  - BACKGROUND: A mechanical aortic prosthesis (MAP) may cause platelet activation
      secondary to shear forces, and the release of adenosine diphosphate (ADP). This
      platelet-mediated event may lead to arterial embolism. Traditionally, warfarin
      has been used to treat such cases, although this anticoagulant has no inhibitory
      effects on platelets. The study aim was to determine if antiplatelet agents could
      prevent thromboembolic events in patients with a MAP. METHODS: Since 2001, a
      total of 265 patients (average age 64.5 +/- 12.0 years), each of whom received a
      MAP with or without additional aortic surgery, was followed at the authors'
      institution. Patients received a loading dose of clopidogrel or prasugrel +
      asprin 325 mg and tested for platelet inhibition. The maintenance dose was 75 mg
      clopidogrel or 10 mg prasugrel + 81 mg aspirin. Platelet reactivity was tested,
      using two different methods, after one month and at six-month intervals
      thereafter. RESULTS: The average follow up was 47.3 +/- 44.3 months; total follow
      up was 11,688.8 months [974 patient-years (pt-yr)]. Over a 16-year period 51
      patients died, primarily from myocardial infarction. Twelve patients had strokes
      (1.2%/pt-yr); of these patients, 10 had discontinued the antiplatelet medication
      (and were receiving warfarin). One patient was nonresponsive to clopidrogel and
      another (a compliant patient) was never tested. Strokes were not observed in
      compliant patients who responded to antiplatelet agents. Thirteen patients had
      gastrointestinal bleeding, four required transfusion, and three died due to
      cerebral aneurysms. CONCLUSIONS: Platelet-mediated thromboembolism following MAP
      installation can be treated with antiplatelet agents. The 16-year results of the
      present study suggested that antiplatelet agents can reduce thromboembolic events
      in patients with MAP. Strokes can be prevented in patients with MAP if treated
      with the correct antiplatelet agent, if the patient responds to the agent
      employed and is strictly compliant.

PMID- 30207123
TI  - Red Cell Distribution Width as a Prognostic Marker in Patients Undergoing Valve
      Surgery.
AB  - BACKGROUND: Numerous studies have shown that elevated red cell distribution width
      (RDW) is associated with poor outcomes in patients with cardiovascular diseases
      such as acute myocardial infarction, stroke, and chronic heart failure. The
      prognostic utility of RDW in patients with valvular disease undergoing heart
      valve surgery is unknown. METHODS: A prospective study was conducted on a group
      of consecutive patients with hemodynamically significant valvular heart disease
      that underwent elective valvular surgery. The preoperative complete blood count,
      data on risk factors, course of operations and the postoperative period were
      assessed. The primary and secondary endpoints were 30-day mortality and any major
      adverse event within 30 days. The data were analyzed with Kaplan-Meier survival
      curves, regression analyses, and receiver operator characteristic (ROC) curves.
      RESULTS: The study group included 500 consecutive patients who underwent
      replacement or repair of the valve/valves. Sixteen patients died during the
      follow up period. On multivariate analysis, creatinine (p = 0.04), red blood cell
      (RBC) count (p = 0.005) and RDW (p = 0.02) were each associated with an increased
      risk of death. The composite endpoint occurred in 208 patients. On multivariate
      analysis, chronic kidney disease (p = 0.003), raised pulmonary blood pressure (p
      = 0.02) and RDW (p = 0.001) remained independent predictors of the secondary
      endpoint. The preoperative RDW in patients with valvular disease undergoing valve
      surgery, combined with EuroSCORE II, predicted 30-day mortality significantly
      better than did EuroSCORE II alone. CONCLUSIONS: An elevated RDW is associated
      with a worse outcome following valve surgery. The predictive ability of the RDW,
      when assessed by the area under the ROC curve, improved the predictive ability of
      the EuroSCORE II calculator.

PMID- 30207124
TI  - Early Experience with the Latest-Generation Biological Prosthesis, the Trifecta?
      GT.
AB  - BACKGROUND: The study aim was to assess the hemodynamic results and implantation
      technique for the latest-generation St. Jude Medical aortic valve bioprosthesis,
      the TrifectaTM GT, which was first marketed in 2016. METHODS: The first 100
      patients (mean age 74.59 +/- 7.41 years) undergoing aortic valve replacement
      (AVR) with the Trifecta GT, whether associated or not with other procedures, were
      included and assessed. All patients underwent a baseline ultrasound scan prior to
      hospital discharge to monitor postoperative gradients and the presence of
      periprosthetic leakage. RESULTS: The predominant valvular heart disease was
      aortic stenosis (85%). An isolated AVR was required in 43% of patients. The
      prosthesis sizes used were 19, 21, 23, 25, and 27 mm. The overall hospital
      mortality was 5%; all deaths occurred in patients with associated surgeries. Peak
      gradients measured prior to hospital discharge ranged from 17.95 mmHg to 10.95
      mmHg for 19 mm and 27 mm prostheses, respectively; mean gradients were 9.94 and
      6.18 mmHg for 19 mm and 27 mm prostheses, respectively. Neither implant-related
      complications nor significant periprosthetic leakages were recorded. CONCLUSIONS:
      Based on experience with patients, the Trifecta GT demonstrated an excellent
      hemodynamic performance after implantation, which involved a simple and safe
      technique. Further long-term studies to determine the durability of the
      prosthesis are required.

PMID- 30207125
TI  - MitraClip(r) Implantation Under Cerebral Protection: A Case Report.
AB  - MitraClip(r) implantation is commonly used in patients with severe mitral
      regurgitation (MR) and who are at high risk for surgical mitral valve repair. The
      occurrence of stroke or transient ischemic attack is a potential complication in
      patients undergoing MitraClip implantation, and incidences of up to 2.6% have
      been reported. Herein is reported the case of an 84-year-old woman with severe MR
      and a thin filamentous structure at the rim of the left atrial appendage of
      unknown etiology. Due to a high surgical risk, the heart team decided to perform
      endovascular mitral valve repair using the MitraClip procedure. In order to
      prevent stroke, the implantation procedure was performed using a cerebral
      protection system.

PMID- 30207126
TI  - Mitral Valve Malignant Primary Tumor as a Surgical Emergency: Case Report.
AB  - Malignant primary tumors of the heart are among the most unusual forms of cancer.
      Cardiac malignancy accounts for about 20% of all primary cardiac tumors, with
      most arising from the atria and less frequently the ventricles; very unusual
      locations include the great vessels and the cardiac valves. A rare case is
      presented of a young female that arrived at the authors' emergency room in
      pulmonary edema and circulatory collapse secondary to a true tumor of the mitral
      leaflets that caused severe mitral valve stenosis. On pathological examination
      this proved to be a mitral leaflet angiosarcoma.

PMID- 30207127
TI  - The Modified Ross Procedure with Prosthetic Graft Wrap Does Not Prevent Autograft
      Failure.
AB  - The modified Ross procedure, which involves replacement of the aortic valve with
      a pulmonary autograft root supported within a Dacron tube graft, was developed
      with the goal of preventing late autograft dilatation and associated aortic
      insufficiency. The case is reported of an adult patient who had a bicuspid aortic
      valve (BAV), underwent a modified Ross procedure, and developed severe aortic
      insufficiency within one year and subsequently required reoperation for aortic
      valve replacement. While advances have been made to increase the success of the
      Ross procedure via modifications to prevent aortic root dilatation, no
      modifications have yet been devised to improve the ability of the pulmonary valve
      to withstand systemic aortic pressures. The Ross procedure has significant
      advantages for children, but the risks and benefits should be carefully
      considered in adults, especially in those with BAV.

PMID- 30207128
TI  - Congenital Left Ventricular-Right Atrial Communication Gerbode-Type Defect.
AB  - Adult congenital heart diseases present a unique challenge in assessing right
      sided cardiac chambers, where pressures can be mistakenly calculated using
      standard echocardiographic formulae. A challenging case is presented of a
      combined inlet ventricular septal defect and ventriculo-atrial Gerbode defect.
      The diagnosis of such adult congenital heart diseases requires an in-depth
      understanding of cardiac pathophysiology and hemodynamics. Video 1: Transthoracic
      echocardiography. Apical four-chamber view, showing a large inlet VSD with
      bidirectional shunt (Eisenmenger syndrome). Video 2: Transthoracic
      echocardiography showing the Gerbode defect in a short-axis view.

PMID- 30207129
TI  - The Perceval Sutureless Valve in Aortic Root Reoperation.
AB  - The case is reported of a 62-year-old man with severe aortic regurgitation that
      was related to failed prior valve-sparing ascending aortic aneurysm repair, and
      who was successfully treated with a Perceval Sutureless valve.

PMID- 30207130
TI  - Sternal-Sparing Aortic Valve Replacement in a Patient with Osteogenesis
      Imperfecta: A Case Report.
AB  - The case described here is the first reported case of successful isolated aortic
      valve replacement (AVR) via a right anterior thoracotomy (RAT) in a patient with
      osteogenesis imperfecta (OI). The most common reported complication in patients
      with OI undergoing AVR or other cardiac surgery is bleeding and sternal
      complications. By using a RAT approach, it was possible to replace the aortic
      valve without major bleeding, transfusion, or sternal complications.

PMID- 30207131
TI  - Rapid Assessment of Avoidable Blindness-Past, Present, and Future.

PMID- 30207132
TI  - LMA(r) ProtectorTM Airway. First experience with a new second generation
      laryngeal mask.
AB  - BACKGROUND: The LMA ProtectorTM Airway (LMA-Protector) is a new supraglottic
      airway promising a better seal, an improved drainage of gastric secretions and
      the opportunity of a simplified fiberscopic guided tracheal intubation. The aim
      of this study was to present a primary evaluation of the LMA-Protector in a
      clinical setting. METHODS: After informed consent 50 patients, scheduled for
      minor/moderate surgery in supine position, were recruited. Pharyngeal seal
      pressures were examined in neutral position of the patients  head and in maximum
      passive extension of the neck. Additionally the fiberscopic view on the glottis
      was graduated and the feasibility of fiberscope guided tracheal intubation
      through the device was evaluated. RESULTS: The median pharyngeal seal pressure of
      the LMA-Protector in neutral position of the head was 34 cmH2O. Passive extension
      of the neck did not cause a reduction of the pharyngeal seal (median pharyngeal
      seal pressure: 34.7 cmH2O; p< 0.039). The LMA-Protector was applicable for
      fiberscopic tracheal intubation, but is not reliable for blind tracheal
      intubation. CONCLUSIONS: The LMA-Protector provides a high pharyngeal seal.
      Uncommon for laryngeal masks its pharyngeal seal is not affected by the extension
      of the patient s neck. As a second generation supraglottic airway which is also
      suitable for simplified fiberscopic guided tracheal intubation, the LMA-Protector
      could be considered as a supraglottic airway of the third generation.

PMID- 30207133
TI  - Plasma levels of mid-regional pro-adrenomedullin in sepsis are associated with
      risk of death.
AB  - BACKGROUND: Identifying ICU patients with sepsis and predicting the risk of death
      are unmet clinical needs. METHODS: Prospective observational singlecenter study
      of 120 consecutive ICU patients with suspected severe sepsis at Jerez Hospital.
      Epidemiological, clinical, laboratory data and MRproADM, Procalcitonin (PCT) and
      Creactive protein (CRP) levels were recorded at ICU admission and followup.
      RESULTS: At ICU discharge, 104 patients were diagnosed with severe sepsis and 39
      died. Plasma MRproADM was highly indicative of sepsis: 4.05 nmol/l vs of 0.309
      nmol/l (p < 0.001), with area under the ROC curve (AUCROC) was 0.947. At 48 hours
      following admission, the median MRproADM levels in surviving sepsis patients fell
      to 1.65 nmol/l but remained higher in the nonsurvivors (2.475 nmol/l) (p = 0.04).
      On day 5 the levels fell to 1.36 nmol/l in surviving sepsis patients vs 3.42
      nmol/l in the non survivors (p<0.001). On day 5 the survivors showed greater
      MRproADM clearance (62.7% vs 21.2%). The AUCROC on day 5 was 0.825, PCT 0.725 and
      CRP 0.700. The AUCROC to MRproADM clearance on day 5 was 0.734. In a
      multivariable model, MRproADM levels at 48 hours and on day 5 and clearance on
      day 5 following admission were statistically significant predictive factors of
      mortality. CONCLUSIONS: In clinical practice, in ICU patients admitted with SIRS
      and organ dysfunction, an MRproADM cutoff point of 1.425 nmol/l helps to identify
      those with sepsis. An MRproADM value above 5.626 nmol/l 48 hours after admission
      was associated with a high risk of death.

PMID- 30207134
TI  - Effect of ultrasound image enhancement software on the quality of vision of
      regional anesthesia needles.
AB  - BACKGROUND: Our objective was to evaluate and compare the visualization of
      different types of needles with or without ultrasound image enhancement software,
      both in biological tissues and artificial models. METHODS: This is an
      observational study on fresh porcine tissue and gelatin models. Six types of
      plexus needles were studied. The same anesthesiologist performed inplane
      punctures with each needle at 30 degrees , 40 degrees  and 50 degrees  in both 2D
      mode and using software-based enhanced mode without changing position, generating
      72 images. The images were evaluated blind by 38 anesthesiologists with at least
      2 years of experience in ultrasound and rated from 0 to 10. A univariate and
      multivariate analysis was performed to identify differences between the images
      according to needle, mode, angle and experimental model. We described the results
      as mean (standard deviation). RESULTS: The Echoplex needle, 8.31 (1.94), was
      significantly better than the Sonoplex needle, 7.53 (2.16), p = 0.0003, and both
      were significantly better than the other needles (p < 0.0001). Significant
      differences were also found in favor of the gelatin model, 7.26 (2.48) vs 6.24
      (3.67), p < 0.0001, and with ultrasound image enhancement software, 8.59 (1.55)
      vs 4.91 (3.31), p < 0.0001. These differences were confirmed by multivariate
      analysis. CONCLUSIONS: Although there are differences between the different types
      of Needles used with ultrasound visualization strategies, ultrasound image
      enhancement software provides good visualization, regardless of the model chosen.

PMID- 30207135
TI  - Ultrasound-guided mandibular nerve block with local anesthetic and low-molecular
      weight dextran helps reduce anesthetic requirements for parotidectomy.

PMID- 30207136
TI  - Effects of dexmedetomidine on inflammatory mediators after tourniquet-induced
      ischemia-reperfusion injury: a randomized, double-blinded, controlled study.
AB  - BACKGROUND: Tourniquet use during total knee arthroplasty (TKA) produces ischemia
      reperfusion injury (IRI), with systemic release of inflammatory cytokines and
      reactive oxygen species upon tourniquet release. We conducted a randomized,
      placebo-controlled, double-blind trial to examine whether dexmedetomidine (DEX)
      as an adjunct during general anesthesia in patients undergoing unilateral TKA
      could attenuate the rise in inflammatory cytokines and oxidative stress. METHODS:
      Sixty-eight patients were randomized to either the control or DEX group. DEX was
      administered at a loading dose of 0.5 MUg/kg, followed by an infusion of 0.4
      MUg/kg/h. We measured serum levels of malondialdehyde (biomarker of oxidative
      stress) and proinflammatory cytokines (interleukin-6 [IL-6] and tumour necrosis
      factor-alpha [TNF-alpha]) pre- induction (baseline), 60 and 90 min post
      tourniquet release. We also assessed hemodynamics, intraoperative remifentanil
      consumption, and postoperative pain scores and analgesic consumption. RESULTS:
      Malondialdehyde was higher than baseline after tourniquet release in both groups
      (p <= 0.001), but the levels were similar between groups at all times. TNF-alpha
      was significantly higher than baseline at 60 min post-tourniquet release only in
      the control group (p = 0.009). Serum IL-6 increased significantly above baseline
      at 60 and 90 min post-tourniquet release in both groups (p < 0.001). At 90 min,
      IL-6 was significantly lower in the dexmedetomidine group than in the control
      group (p = 0.049). Remifentanil consumption, heart rate, and pain scores were
      significantly lower in the dexmedetomidine group. CONCLUSIONS: Our results
      suggest that dexmedetomidine as an adjunct to general anesthesia attenuated the
      rise in proinflammatory cytokines, providing protective effects in tourniquet-
      induced IRI.

PMID- 30207137
TI  - Pectoral Nerve block II with programmed intermittent bolus of local anesthetic
      and post-operative pain relief in breast surgery.

PMID- 30207138
TI  - Human Intestinal Microbiota: Role in Development and Functioning of the Nervous
      System.
AB  - Recent results related to investigation of the role of intestinal microbiota (IM)
      in development andfunctioning of the human nervous system are discussed. The role
      of the microbiota in bidirectional communicationbetween the gastrointestinal
      tract and the central nervous system is considered. Special attention ispaid to
      the primary IM of infants, which is actively involved in formation of immune and
      other physiologicalmechanisms, including the nervous system, and is responsible
      for the subsequent general and psychicalhealth of a human. The results of
      research on ability of the commensal intestinal microflora to produce
      neuroactivecompounds, including neurotransmitters, short- and long-chain fatty
      acids, gamma-aminobutyric acid,etc., are summarized. These compounds may have a
      considerable effect on development and functioning ofthe central nervous system,
      including the brain. Research on various animal models is discussed,
      includinginvestigation of IM effect on behavior, learning abilities and memory,
      anxiety and depression levels, reactionto emotional stimuli, and stress
      resistance. A special section deals with probiotic bacteria, which are
      presentlyconsidered as psychobiotics with preventive and therapeutic potential
      for treatment of neurological and neurophysiologicaldisorders. Development of new
      paradigms and concepts, rejection of some classical conceptsof neurobiology is
      presently the key condition for the future breakthrough in investigation of human
      nervousactivity.

PMID- 30207139
TI  - Genetic Polymorphism of Sherry Saccharomyces cerevisiae Yeasts.
AB  - The review deals with natural diversity of sherry ("flor") Saccharomyces
      cerevisiae yeasts. Variousproperties of these yeasts are analyzed: life cycles,
      fermentation of sugars, sensitivity to methyl violet and killertoxins, and
      resistance to ethanol and sulfite. Special attention is paid to molecular
      identification and differentiationof sherry yeasts. The history of their
      nomenclature is considered, including the names of possiblesubpopulations:
      "aceti," "beticus" ("cheresienses"), "cordubensis," "gaditensis," "hispanica"
      ("prostoserdovii"),and "oxidans."

PMID- 30207140
TI  - Effect of polyethylenimine-based sorbents on the luminescence of photobacteria.

PMID- 30207141
TI  - Sporulation of Bacillus subtilis in Binary Cultures with Ultramicrobacteria.
AB  - The effect of ultramicrobacterial epibionts of the genera Kaistia (strain NF1),
      Chryseobacterium(strain NF4), and Stenotrophomonas (strain FM3) on the process of
      sporulation of Bacillus subtilis ATCC6633 was studied. The investigated strains
      of ultramicrobacteria (UMB) were found to inhibit the sporulationprocess of B.
      subtilis ATCC 6633 in binary mixed cultures, exhibiting a 3-day delay of the
      onset of sporulationcompared to the control one, an extended period of the
      prospore maturation, formation of the fraction ofimmature spores, and development
      of ultrastructural defects in many endospores. Thus, investigation ofbinary mixed
      cultures of B. subtilis and UMB revealed that, apart from suppression of
      reproduction and lysisof host vegetative cells, inhibition of spore formation and
      destruction of endospores was yet another featureof intermicrobial parasitism.
      The UMB parasites of the studied genera are assumed to participate in the
      regulationof development and reproduction of B. subtilis in natural habitats of
      this spore-forming bacterium.

PMID- 30207142
TI  - Formation of Pectobacterium carotovorum biofilms depending of the carbon source.
AB  - Microbial biofilms are a basic form of existence of bacteria in the environment,
      as well as in the animal and plant organisms. The patterns of biofilm formation
      depending on cultivation conditions is presently insufficiently studied. This
      paper presents experimental results on the effect of carbon sources on biofilm
      formation and movement on the swarming type in a phytopathogenic bacterium
      Pectobacterium carotovorum. A polyol inositol was shown to cause a significant
      activation of these processes.

PMID- 30207143
TI  - Characterization of the lipopolysaccharide of Escherichia coli 126.
AB  - The lipopolysaccharide (LPS) of Escherichia coli 126 was isolated and studied.
      The lipid A fatty acid composition of the investigated LPS was similar to that of
      other members of the family Enterobacteriaceae. The E. coli 126 LPS was more
      toxic than the LPSs of previously studied E. coli strains and of other members of
      the Enterobacteriaceae (Budvicia aquatica and Pragia fontium), and was less
      pyrogenic than pyrogenal. SDS-PAG electrophoresis showed a bimodal distribution
      typical of S-form LPSs. The LPS of E. coli 126 decreased the adhesive index
      indicating a possible competition between LPS molecules of E. coli 126 and
      adhesins of E. coli F-50 on rabbit erythrocytes. The LPS of E. coli 126 in a
      homologous system showed antigenic activity in the reactions of double
      immunodiffusion in agar by Ouchterlony. No serological cross-reaction of the LPS
      of other E. coli strains, as well as of that of the B. aquatica type strain, with
      the antiserum to E. coli 126 was observed. The structural components of the
      lipopolysaccharide obtained by mild acid hydrolysis were lipid A, the core
      oligosaccharide, and the O-specific polysaccharide. Based on the data of
      monosaccharide analysis and 1H and 13C NMR spectroscopy it was found that the O
      specific polysaccharide had the structure characteristic of the representatives
      of E. coli serogroup O15.

PMID- 30207144
TI  - Effect of chromate ions on marine microalgae Phaeodactylum tricornutum.
AB  - Effect of chromate ions on the culture of a marine diatom Phaeodactylum
      tricornutum was studied using an M-PEA-2 fluorimeter, which carries out
      simultaneous measurement of fluorescence induction and redox transformations of
      the P700 pigment within a millisecond range. Chromate ions were shown to inhibit
      electron transport in PS II and decrease the rate of QA reduction. This results
      in decreased values of the quantum yield of electron transport in PS II (phiEo)
      and performance index (PI ABS), lower rates of P700 reduction, and increased
      energy (DI0/RC) and DeltapH-dependent nonphotochemical quenching (q E ).
      Emergence of the slow component of P700 reduction was observed, indicating the
      activation of cyclic transport in the presence of chromate. Performance index (PI
      ABS), which was the most sensitive parameter, may be recommended for detection of
      chromate ions at early stages of their toxic action. The fluorescence parameter F
      O is promising application in biotesting to assess the algal growth rates.

PMID- 30207145
TI  - Epiphytic microorganisms degrading aromatic hydrocarbons from the phyllosphere of
      urban woody plants.
AB  - From the leaves of three urban trees (Tilia sp., Acer sp., and Fraxinus sp.), 180
      strains degrading phenanthrene, naphthalene, and salicylate were isolated by
      direct plating and enrichment cultures. The leaves of each tree species were
      characterized by a specific profile of aromatic hydrocarbon-degrading microflora.
      Members of the type Actinobacteria were predominant in the case of direct plating
      on media with phenanthrene and naphthalene. Enrichment cultures with phenanthrene
      and salicylate were shown to yield microbial consortia, the composition of which
      changed with time. Members of the type Proteobacteria were predominant in these
      consortia. No plasmids of polycyclic aromatic hydrocarbon degradation of the P-7
      and P-9 incompatibility groups were revealed in the studied strains.

PMID- 30207146
TI  - Genome analysis of Acidiplasma sp. MBA-1, a polyextremophilic archaeon
      predominant in the microbial community of a bioleaching reactor.
AB  - Results of genome analysis of a member of the family Ferroplasmaceae, Acidiplasma
      sp. strain MBA-1, an extremely acidophilic, moderately thermophilic archaeon
      oxidizing ferrous iron under oxic conditions and utilizing organic compounds.
      This strain was previously shown to predominate in the community carrying out
      biooxidation of pyrite-arsenopyrite gold-bearing concentrate. The genome was
      sequenced using the Illumina HiSeq 2000 platform. A total of 2306800 pairwise
      reads were obtained, corresponding to 300-fold coverage. Assembly was carried out
      by three programs in parallel. The optimal assembly contained nine contigs, the
      genome size was 1747364 bp, and N50 was 446845 bp. Annotation of the genome
      revealed 1749 protein-encoding sequences, as well as 46 tRNA genes and one rRNA
      gene copy. The results of genome analysis confirmed the previous data on the
      physiology of this organism. The gene of sulfocyanin (TZ01_06185), a blue copper
      containing protein playing the key role in the iron-oxidizing electron transport
      chain, was identified in the genome. The genes encoding sulfur oxidoreductase
      (TZ01_04750) and sulfateadenilyl transferase (TZ01_04545), the enzymes of sulfur
      oxidation, were also identified. The genes involved in the transport and
      catabolism of organic compounds and the genes of the 3-hydroxypropionate/4
      hydroxybutyrate cycle were revealed. The genome of Acidiplasma sp. MBA-1 is the
      first genome of this genus deposited to a public database DDBJ/EMBL/GenBank
      (accession no. JYHS00000000) and is of interest for further investigation of
      Acidiplasma archaea.

PMID- 30207147
TI  - A novel Delftia plant symbiont capable of autotrophic methylotrophy.
AB  - A facultative methylotrophic bacterium, strain Lp-1, which was isolated from root
      nodules of lupine (Lupinus polyphyllus L.) on the medium with methanol as a
      carbon and energy source, exhibited high similarity of the 16S rRNA gene
      sequences to Delftia strains (94-99.9%). The cells of Delftia sp. Lp-1 were
      motile gram-negative rods dividing by binary fission. Predominant fatty acids
      were C16:0 (34.2%), C16:1omega9 (14.5%), and C18:1omega7c (17.3%).
      Phosphatidylethanolamine, phosphatidylcholine, and phosphatidylglycerol were the
      dominant phospholipids. Q8 was the major ubiquinone. Optimal growth occurred at
      24-26 degrees C and pH 7.1-7.3; growth was inhibited by 1% NaCl. The organism
      oxidized methanol with the classical methanol dehydrogenase and used the ribulose
      bisphosphate pathway of C1 metabolism. Analysis of translated amino acid sequence
      of the large subunit of the MxaF methanol dehydrogenase revealed 85.5-94%
      similarity to the sequences of such autotrophic methylotrophs of the class
      Alphaproteobacteria as Angulomicrobium, Starkeya, and Ancylobacter, indicating
      the possible acquisition of the mxaF gene via horizontal gene transfer. Delftia
      sp. Lp-1 (VKM B-3039, DSM 24446), the first methylotrophic member of the genus
      Delftia, was shown to be a plant symbiont, stimulating plant growth and
      morphogenesis, increasing the level of photosynthetic pigments and specific leaf
      weight. It possesses the nifH gene of nitrogen fixation, is capable of phosphate
      solubilization, synthesis of auxins and siderophores, and is antagonistic to
      plant pathogenic fungi and bacilli.

PMID- 30207148
TI  - Diversity of magnetotactic bacteria of the Moskva River.
AB  - Diversity of magnetotactic bacteria in the Moskva River at the Strogino area was
      studied using microscopy and phylogenetic analysis. Magnetotactic cocci were the
      predominant morphotype. Phylogenetic analysis of the 16S rRNA gene sequences
      revealed 13 OTUs of the orders Magnetococcales and Rhodospirillales, class
      Alphaproteobacteria. The shares of the relevant sequences were 90 and 10%,
      respectively. An axenic culture of magnetotactic spirilla was isolated from the
      studied community. According to the results of the 16S rRNA gene sequencing, the
      isolate was identified as a new Magnetospirillum species.

PMID- 30207149
TI  - Biodiversity of aerobic methylobacteria associated with the phyllosphere of the
      southern Moscow Oblast.
AB  - During the summer period (15-25 degrees C), 34 strains of methylotrophic bacteria
      associated with differentspecies of herbs, shrub, and trees in Pushchino (Moscow
      oblast, Russia) were isolated on the mediumwith methanol. Predominance of pink
      colored Methylobacterium strains in the phyllosphere of many plantswas confirmed
      by microscopy, enumeration of the colonies from grass leaves, and sequencing of
      the 16SrRNA genes. Colorless and yellow-pigmented methylotrophs belonged to the
      genera Methylophilus, Methylobacillus,Hansschlegelia, Methylopila, Xanthobacter,
      and Paracoccus. All isolates were able to synthesize planthormones auxins from L
      tryptophan (5-50 MUg/mL) and are probably plant symbionts.

PMID- 30207151
TI  - Conformational Dynamics of a Cysteine-Stabilized Plant Defensin Reveals an
      Evolutionary Mechanism to Expose Hydrophobic Residues.
AB  - Sugar cane defensin 5 (Sd5) is a small antifungal protein, whose structure is
      held together by four conserved disulfide bridges. Sd5 and other proteins sharing
      a cysteine-stabilized alpha-beta (CSalphabeta) fold lack a regular hydrophobic
      core. Instead, they are stabilized by tertiary contacts formed by surface-exposed
      hydrophilic and hydrophobic residues. Despite excessive cross-links, Sd5 exhibits
      complex millisecond conformational dynamics involving all secondary structure
      elements. We used Carr-Purcell-Meiboom-Gill (CPMG) NMR relaxation dispersion (RD)
      measurements performed at different temperatures and denaturant concentrations to
      probe brief excursions of Sd5 to a sparsely populated "excited" state.
      Temperature-dependent CPMG RD experiments reveal that the excited state is
      enthalpically unfavorable, suggesting a rearrangement of stabilizing contacts
      formed by surface-exposed side chains and/or secondary structure, while the
      experiments performed at different denaturant concentrations suggest a decrease
      in accessible surface area of Sd5 in the excited state. The measured backbone 15N
      chemical shift changes point to a global conformational rearrangement such as a
      potential alpha- to beta-transition of the Sd5 alpha-helix or other major
      secondary structure reorganization and concomitant conformational changes in
      other parts of the protein. Overall, the emerging picture of Sd5 dynamics
      suggests this protein can populate two alternative well-ordered conformational
      states, with the excited conformer being more compact than the native state and
      having a distinct secondary structure and side-chain arrangements. The
      observation of an energetically unfavorable yet more compact excited state
      reveals a remarkable evolution of the CSalphabeta fold to expose and reorganize
      hydrophobic residues, which enables the creation of versatile binding sites.

PMID- 30207150
TI  - Bias-Driven Conductance Increase with Length in Porphyrin Tapes.
AB  - A key goal in molecular electronics has been to find molecules that facilitate
      efficient charge transport over long distances. Normally, molecular wires become
      less conductive with increasing length. Here, we report a series of fused
      porphyrin oligomers for which the conductance increases substantially with length
      by >10-fold at a bias of 0.7 V. This exceptional behavior can be attributed to
      the rapid decrease of the HOMO-LUMO gap with the length of fused porphyrins. In
      contrast, for butadiyne-linked porphyrin oligomers with moderate inter-ring
      coupling, a normal conductance decrease with length is found for all bias
      voltages explored (+/-1 V), although the attenuation factor (beta) decreases from
      ca. 2 nm-1 at low bias to <1 nm-1 at 0.9 V, highlighting that beta is not an
      intrinsic molecular property. Further theoretical analysis using density
      functional theory underlines the role of intersite coupling and indicates that
      this large increase in conductance with length at increasing voltages can be
      generalized to other molecular oligomers.

PMID- 30207152
TI  - Mirrors of Bonding in Metal Halide Perovskites.
AB  - We explore the chemical bonding and band gap in the metal halide perovskites ABX3
      (where A is a cation, B a metal dication, and X a halide) through detailed
      calculations and a qualitative, symmetry-based bonding analysis that moves
      between chemical and physical viewpoints, covering every aspect of bonding over a
      range of 15 eV around the band gap. We show how the gap is controlled by metal
      halide orbital interactions that give rise to a characteristic mirror of bands, a
      bonding signpost which first shows up in turning on and off the scalar
      relativistic effects in computation of the band structure of CsPbBr3. The mirror
      is made up by a Pb 6s and Br 4p combination that moves in an understandable way
      through the Brillouin zone, setting the valence band maximum. The mirror is also
      there when the A cation is changed to an organocation and is robust enough to
      persist through moderate distortions of the lattice. The analysis predicts how a
      modification of Pb2+ to Sn2+ and Ge2+ and a variation of the halide X influence
      the band gap. In describing in equal detail the lowest three conduction bands, a
      second mirror of bonding emerges. For CsPbBr3, this mirror is made up by Pb 6p
      and Br 4p combinations. An understanding of the way these combinations move in
      reciprocal space to set the conduction band minimum allows us to see why the band
      gap is direct. The orbital analysis provides a chemical and intuitive picture of
      band gap engineering in this popular class of materials.

PMID- 30207153
TI  - Investigation of Interface Effect on the Performance of CH3NH3PbCl3/ZnO UV
      Photodetectors.
AB  - Recent investigations indicate that the performance of organic-inorganic
      perovskite optoelectronic devices can be improved by combining the perovskites
      and the inorganic materials. However, very few studies have focused on the
      investigation of perovskites/inorganic semiconductor hybrid UV photodetectors and
      their detailed performance-enhancement mechanism is still not very clear. In this
      work, a CH3NH3PbCl3/ZnO UV photodetector has been first demonstrated and
      investigated. Both the photoresponsivity and response speed of the hybrid device
      are higher than those of pure CH3NH3PbCl3 and ZnO devices. The photoluminescence
      and transient absorption spectra indicate that the photoinduced electron transfer
      between CH3NH3PbCl3 and ZnO should be responsible for the performance enhancement
      of the hybrid device. In addition, the high crystal quality of CH3NH3PbCl3 on ZnO
      film is another important reason for the excellent UV detection performance. Our
      findings in this work provide new insights into the intrinsic photophysics
      essential for perovskite optoelectronic devices.

PMID- 30207154
TI  - para-Aminothiophenol Radical Reaction-Functionalized Gold Nanoprobe for One-to
      All Detection of Five Reactive Oxygen Species In Vivo.
AB  - Five major reactive oxygen species (ROS) are generated in diseases including
      H2O2, *OH, O2*-, ROO*, and 1O2. Simultaneous detection of the five ROS with a
      single probe is crucial for a comprehensive understanding of the development and
      progression of many diseases, such as cancer and inflammatory diseases. However,
      currently reported detection systems are limited by targeting one ROS with one
      probe. This one-to-one detection mode may fail to sufficiently unveil the
      diseased state. In this study, we achieved simultaneous detection of all the five
      ROS with one probe (i.e., one-to-all detection), by designing a novel para
      aminothiophenol (PATP) and hemin-decorated gold (Au/PATP/Hemin) nanoprobe. The
      design is principled by our discovery that PATP can react with *OH, O2*-, ROO*,
      and 1O2 by a radical oxidative coupling mechanism to form 4,4'
      dimercaptoazobenzene (DMAB). The DMAB then elicited strong characteristic surface
      enhanced Raman scattering (SERS) peaks at 1142, 1386, and 1432 cm-1; which in
      turn enables direct detection of *OH, O2*-, ROO*, and 1O2 and indirect detection
      of H2O2 by hemin-catalyzed fenton reaction to convert H2O2 into *OH. In two
      representative ROS-elevated mice models of tumors and allergic dermatitis, the
      Au/PATP/Hemin nanoprobe demonstrated its robust performance of monitoring tumor
      development and inflammation progression in a highly sensitive and quantitative
      manner.

PMID- 30207155
TI  - Characterization of Cerebrospinal Fluid via Data-Independent Acquisition Mass
      Spectrometry.
AB  - Cerebrospinal fluid (CSF) is in direct contact with the brain and serves as a
      valuable specimen to examine diseases of the central nervous system through
      analyzing its components. These include the analysis of metabolites, cells as
      well as proteins. For identifying new suitable diagnostic protein biomarkers
      bottom-up data-dependent acquisition (DDA) mass spectrometry-based approaches are
      most popular. Drawbacks of this method are stochastic and irreproducible
      precursor ion selection. Recently, data-independent acquisition (DIA) emerged as
      an alternative method. It overcomes several limitations of DDA, since it combines
      the benefits of DDA and targeted methods like selected reaction monitoring (SRM).
      We established a DIA method for in-depth proteome analysis of CSF. For this, four
      spectral libraries were generated with samples from native CSF ( n = 5), CSF
      fractionation (15 in total) and substantia nigra fractionation (54 in total) and
      applied to three CSF DIA replicates. The DDA and DIA methods for CSF were
      conducted with the same nanoLC parameters using a 180 min gradient. Compared to a
      conventional DDA method, our DIA approach increased the number of identified
      protein groups from 648 identifications in DDA to 1574 in DIA using a
      comprehensive spectral library generated with DDA measurements from five native
      CSF and 54 substantia nigra fractions. We also could show that a sample specific
      spectral library generated from native CSF only increased the identification
      reproducibility from three DIA replicates to 90% (77% with a DDA method).
      Moreover, by utilizing a substantia nigra specific spectral library for CSF DIA,
      over 60 brain-originated proteins could be identified compared to only 11 with
      DDA. In conclusion, the here presented optimized DIA method substantially
      outperforms DDA and could develop into a powerful tool for biomarker discovery in
      CSF. Data are available via ProteomeXchange with the identifiers PXD010698,
      PXD010708, PXD010690, PXD010705, and PXD009624.

PMID- 30207156
TI  - Monoclonal Antibody Capture and Analysis Using Porous Membranes Containing
      Immobilized Peptide Mimotopes.
AB  - Rapid, convenient methods for monoclonal antibody (mAb) isolation are critical
      for determining the concentrations of therapeutic mAbs in human serum. This work
      uses porous nylon membranes modified with a HER2 peptide mimotope,
      KGSGSGSQLGPYELWELSH (KH19), for rapid affinity capture of Herceptin, a mAb used
      to treat breast cancer. Covalent linking of KH19 to poly(acrylic acid)-containing
      films in porous nylon leads to a Herceptin-binding capacity of 10 mg per mL of
      membrane and allows selective Herceptin capture from diluted (1:3) human serum in
      5 min. Liquid chromatography-mass spectrometry demonstrates the high purity of
      eluted Herceptin. Moreover, the fluorescence intensity of the protein eluted from
      membranes increases linearly with the amount of Herceptin spiked in loading
      solutions containing diluted (1:3) human serum. These results demonstrate the
      promise of mimotope-modified membranes for Herceptin analysis that does not
      require secondary antibodies or derivatization with fluorescent labels. Thus,
      mimotope-containing membranes may form part of a simple benchtop analysis system
      for assessing the concentrations of therapeutic mAbs.

PMID- 30207157
TI  - Highly Conducting Neutral Coordination Polymer with Infinite Two-Dimensional
      Silver-Sulfur Networks.
AB  - Highly crystalline films of a silver-based coordination polymer, [Ag5(C6S6)] n
      (Ag-BHT, BHT = benzenehexathiol), have been prepared. The structure of Ag-BHT,
      solved by combining rotation electron diffraction and powder X-ray diffraction
      techniques, indicates that it has a lamellar structure with alternatively stacked
      two-dimensional Ag-S networks and layers composed of one-dimensional metal
      dithiolene polymers. In addition, the polycrystalline Ag-BHT film shows high
      electrical conductivity of up to 250 S.cm-1 at 300 K. The ultraviolet
      photoelectron spectroscopy and electronic band structure calculations reveal that
      this can be attributed to the partially filled valence band and the unique two
      dimensional Ag-S networks.

PMID- 30207158
TI  - Photophysical Properties of Tetracationic Ruthenium Complexes and Their Ter-Ionic
      Assemblies with Chloride.
AB  - The synthesis of seven ruthenium(II) polypyridyl complexes bearing one dicationic
      bis-4,4'-(trimethylaminomethyl)-2,2'-bipyridine (tmam) ligand is reported. The
      ancillary ligands of each complex were 2,2'-bipyrazine (bpz), 2,2'-bipyridine
      (bpy), 4,4'- tert-butyl-2,2'-bipyridine (dtb), 4,4'-dimethyl-2,2'-bipyridine
      (4,4'-dmb), 5,5'-dimethyl-2,2'-bipyridine (5,5'-dmb), 4,4'-nonyl-2,2'-bipyridine
      (nonyl), and 4,4'-methoxy-2,2'-bipyridine (MeO). The metal-to-ligand charge
      transfer excited state was localized on the tmam ligand in all instances with the
      exception of [Ru(bpz)2(tmam)]4+, where it was localized on the bpz ligand. All
      [PF6]- complexes were shown to form strong ion pairs with chloride in a Ru/Cl 1:2
      stoichiometry in acetone, as evidenced by 1H NMR and UV-visible titrations. With
      the exception of [Ru(bpz)2(tmam)]4+, ion pairing with chloride anions resulted in
      excited states that were ~25% longer-lived and with an ~50% increase in the
      photoluminescence quantum yields compared to the [PF6]- ion pairs. It was shown
      that the quantum yield enhancements originated from a decreased nonradiative rate
      constant and an increased radiative rate constant. [Ru(bpy)2(tmam)]4+ showed
      curious excited state quenching behavior at higher equivalents of chloride, the
      origin of which is not understood.

PMID- 30207159
TI  - All-Oxide-Based Highly Transparent Photonic Synapse for Neuromorphic Computing.
AB  - The neuromorphic system processes enormous information even with very low energy
      consumption, which practically can be achieved with photonic artificial synapse.
      Herein, a photonic artificial synapse is demonstrated based on an all-oxide
      highly transparent device. The device consists of conformally grown In2O3/ZnO
      thin films on a fluorine-doped tin oxide/glass substrate. The device showed a
      loop opening in current-voltage characteristics, which was attributed to charge
      trapping/detrapping. Ultraviolet illumination-induced versatile features such as
      short-term/long-term plasticity and paired-pulse facilitation were truly
      confirmed. Further, photonic potentiation and electrical habituation were
      implemented. This study paves the way to develop a device in which current can be
      modulated under the action of optical stimuli, serving as a fundamental step
      toward the realization of low-cost synaptic behavior.

PMID- 30207160
TI  - An Approach of Utilizing Water-Soluble Carbohydrates in Lignocellulose Feedstock
      for Promotion of Cellulosic l-Lactic Acid Production.
AB  - Agricultural lignocellulose biomass generally contains certain amounts of water
      soluble carbohydrates (WSC) such as glucose, fructose, or sucrose. These sugars
      are generally degraded in pretreatment at high temperature or discharged with
      wastewater in a detoxification process. This study proposed an approach of
      utilizing frequently ignored water-soluble carbohydrates for promotion of
      cellulosic l-lactic acid production. A simple solid state fermentation was
      performed during a corn stover storage period to convert the sugars into l-lactic
      acid and then a dry biorefining technology was applied to convert cellulose and
      hemicellulose fractions into the same l-lactic acid product. The 5
      hydroxymethylfurfural (HMF) formation in pretreatment was significantly reduced
      and the consequent biodetoxification time was shortened. l-Lactic acid production
      was increased from 130.2 g/L to 139.0 g/L, and the minimum l-lactic acid selling
      price was reduced by 5.9%. This study provided an important option of biorefinery
      processing technology for production of value added biochemicals.

PMID- 30207161
TI  - Functionalized Scaffold for in Situ Efficient Gene Transfection of Mesenchymal
      Stem Cells Spheroids toward Chondrogenesis.
AB  - Multicellular mesenchymal stem cell (MSC) spheroids possess enhanced
      chondrogenesis ability and limited fibrosis, exhibiting advantage toward hyaline
      like cartilage regeneration. However, because of the limited cell surfaces in
      spheroid exposed to DNA/vector, it is difficult to realize efficient gene
      transfection, most of which highly rely on cell-substrate interaction. Here, we
      report a poly(l-glutamic acid)-based porous scaffold with tunable inner surfaces
      that can sequentially realize cell-scaffold attachment and detachment, as well as
      the followed in situ spheroid formation. The attachment and detachment of cells
      from scaffold is achieved by the capture and release of fibronectin (Fn) via
      reversible imine linkage between aromatic aldehyde groups of scaffold and amino
      groups of Fn. Together with N, N, N-trimethyl chitosan chloride condensing
      plasmid DNA encoding transforming growth factor-beta1 (pDNA-TGF-beta1), cell
      attachment realizes efficient surface-mediated gene transfection. Conversion of
      scaffold stiffness can affect the adhesion shape of cells. Stiffer scaffold
      reinforces the adhesion, leading to the amplification of peripheral focal
      adhesions and the promotion of cell spreading, as well as the promotion of gene
      transfection efficiency. After cellular detachment from the scaffold via lysine
      treatment, the subsequent spheroid formation with extensive cell-cell interaction
      up-regulates the corresponding protein expression with a prolonged term. With the
      induction effect of the expressed TGF-beta1, significantly enhanced
      chondrogenesis of MSCs in spheroids is achieved at 10 d in vitro. Well
      regenerated cartilage at 8 weeks in vivo indicates that the present gene
      transfection system is a platform that can be potentially applied toward
      cartilage tissue engineering.

PMID- 30207162
TI  - Impact of biological matrix on inflammatory protein biomarker quantification
      based on targeted mass spectrometry.
AB  - BACKGROUND: Serum and plasma are widely used matrices in biological and clinical
      studies. To improve reliability and consistency of markers quantification, the
      influence of these matrices on proteins was evaluated by targeted mass
      spectrometry. RESULTS: 65 proteins were quantified in matched blood samples
      collected in serum, ethylenediaminetetraacetic acid and heparin plasma tubes from
      40 healthy and 10 pathological individuals. Only 52% of the proteins were not
      impacted by any of the biological matrices tested, and the effects on
      quantification of proteins affected was matrix and protein dependent. CONCLUSION:
      Matrix comparisons using mass spectrometry is therefore recommended to assess the
      relevance of using surrogate matrix, performing biomarker discovery study or
      evaluating the clinical use of biomarkers in large clinical cohorts.

PMID- 30207163
TI  - Treatment satisfaction in women receiving palbociclib combination therapies for
      advanced/metastatic breast cancer.
AB  - AIM: To understand treatment satisfaction in patients with advanced or metastatic
      breast cancer receiving palbociclib plus an aromatase inhibitor or palbociclib
      plus fulvestrant in a real-world setting. PATIENTS & METHODS: We performed an
      observational, cross-sectional, web-based survey of 604 patients with self
      reported hormone receptor-positive (HR+)/HER2-negative (HER2-) ABC/mBC in six
      countries. RESULTS: Overall, more than 96% of patients reported the benefits of
      their palbociclib combination therapy met or exceeded their expectations. Patient
      expectations and satisfaction with therapy did not differ between patients on
      palbociclib plus letrozole and palbociclib plus fulvestrant, or between patients
      with visceral and nonvisceral metastases. CONCLUSION: The patients on palbociclib
      combination therapy reported high satisfaction scores across multiple countries.

PMID- 30207164
TI  - Use of the Delphi Technique to Obtain Community Input on Leading Contributors to
      Early Childhood Obesity in Latino Communities.
AB  - INTRODUCTION:: In the United States, Latino children are disproportionately
      affected by childhood obesity and related comorbidities. Stakeholder engagement
      has the potential to heighten the efficacy of interventions, thereby reducing the
      disparate prevalence of obesity among Latino children. The objective of this
      study was to identify stakeholders' opinions on factors influencing early
      childhood obesity in Latino children aged 0 to 5 years. METHOD:: This study used
      the Delphi technique to gather and prioritize stakeholders' opinions about the
      factors and barriers considered most influential in early (age 0-5 years)
      childhood obesity intervention or prevention within the Latino community. Three
      sequential phases were used. Participants included Latina women as well as staff
      from community organizations serving Denver metropolitan's Latino population.
      RESULTS:: Study results revealed that stakeholders value the role of the child's
      primary care provider in the identification of overweight children and desire
      more educational support to reduce intake of nonnutritious foods. Participants
      further determined that obesity-related knowledge gaps and affordability of
      healthy foods and activities were the largest barriers to helping Latino children
      maintain healthy weights. CONCLUSION:: Use of this stakeholder-informed data
      could assist in the development of future culturally tailored interventions aimed
      at reducing the rates of early childhood obesity in the Latino population.

PMID- 30207165
TI  - Impact of MPO-ANCA mediated oxidative imbalance on renal vasculitis.
AB  - Glomerulonephritis is a severe complication of microscopic polyangiitis (MPA), a
      small-vessel vasculitis associated with anti-myeloperoxidase antibodies (MPO
      ANCA). We previously showed the pathogenic effects of MPO-ANCA that activate MPO
      to trigger an oxidative burst mainly through HOCl production, contributing to
      endothelial injury and lung fibrosis. The aim of this study was to investigate
      the relationship between MPO-induced oxidative stress, anti-oxidant defenses and
      renal histological lesions in MPA patients. We therefore analyzed histological
      data from a prospective cohort of ANCA-associated glomerulonephritis. Serum
      mediated HOCl production, advanced oxidation protein products (AOPP), and thiol
      concentration in sera were determined. From 38 patients included, histological
      classification noted 50% focal glomerulonephritis, 15.8% crescentic
      glomerulonephritis, and 34.2% mixed-glomerulonephritis. MPA patients' sera
      displayed higher HOCl production by MPO (p<0.001), higher AOPP (p<0.001) and
      thiol (p<0.01) levels, compared with healthy subjects. The presence of cellular
      crescents was associated with higher serum-mediated HOCl production (p=0.049) and
      lower thiol levels (p=0.022) at disease onset. Higher thiol concentrations were
      associated with focal glomerulonephritis (p=0.042), less interstitial fibrosis
      (p=0.039) and hyalinosis (p=0.066). In remission, HOCl production was decreased
      (p<0.01), and thiol concentration remained high (p=0.39). Our findings suggest
      that HOCl production by activated MPO could contribute to the very early stage of
      glomerulonephritis, whereas thiol may exert a protective effect against the
      development of renal vasculitis and glomerulosclerosis. This study highlights the
      importance of oxidative defenses to counteract the process of MPO-ANCA associated
      glomerulonephritis.

PMID- 30207166
TI  - NIX-mediated mitophagy protects against proteinuria-induced tubular cell
      apoptosis and renal injury.
AB  - Proteinuria, the most common symptom of renal injury, is an independent factor
      for renal tubular injury. However, the underlying mechanism remains to be fully
      elucidated. Mitochondrion is an important target for proteinuria-induced renal
      tubular cell injury. Insufficient mitophagy exacerbates cell injury by initiating
      mitochondrial dysfunction-related cell apoptosis. In the experiment, the role of
      NIX-mediated mitophagy was investigated in proteinuria-induced renal injury. In
      this study we demonstrated NIX expression was reduced in renal tubules and
      correlated with decline of eGFR and increase of the proteinuria in patients. In
      proteinuric mice, NIX-mediated mitophagy was significantly suppressed. Meanwhile,
      the proteinuric mice exhibited renal dysfunction, increased mitochondrial
      fragmentation and tubular cell apoptosis. Overexpression of NIX attenuated those
      disruptions in proteinuric mice. In cultured renal tubular epithelial cells,
      albumin induced decrease in NIX-mediated mitophagy and increase in cell
      apoptosis. Overexpression of NIX attenuated albumin-induced cell apoptosis
      whereas NIX siRNA aggravated these perturbations. These results indicate that
      proteinuria suppresses NIX-mediated mitophagy in renal tubular epithelial cell,
      which triggers the cell undergoing mitochondria-dependent cell apoptosis.
      Collecting, our finding suggests that restoration of NIX-mediated mitophagy might
      be a novel therapeutic target for alleviating proteinuria-induced kidney injury.

PMID- 30207167
TI  - Caveolae Facilitate TRPV4-mediated Ca2+ Signaling and the Hierachical Activation
      of Ca2+-activated K+ Channels in K+-secreting Renal Collecting Duct Cell.
AB  - TRPV4-mediated Ca2+ signaling induces early activation of small/intermediate Ca2+
      activated K+ channels, SK3 (KCNN3) and IK1 (KCNN4), that leads to membrane
      hyperpolarization and enhanced Ca2+ influx that is critical for subsequent
      activation of the large conductance Ca2+-activated K+ channel BK (KCNMA1) and K+
      secretion in kidney cortical collecting duct (CCD) cells. The focus of the
      present study was to determine if such coordinated hierarchical /sequential
      activation of these channels in CCD was orchestrated within caveolae, a known
      microcompartment underlying selective Ca2+-signaling events in other cells. In K+
      secreting mouse principal cell (PC) line, mCCDcl1 cells, knockdown of caveolae
      caveolin-1 (CAV-1) depressed TRPV4-mediated Ca2+ signaling and activation of SK3,
      IK1 and BK. Immunofluorescence co-localization analysis and co
      immunoprecipitation assays demonstrated direct coupling of TRPV4 with each of the
      KCa channels in both mCCDcl1 and whole mouse kidney homogenates. Likewise,
      extending this analysis to CAV-1 demonstrate co-localization and direct coupling
      of CAV-1 with TRPV4, SK3, IK1, and BK providing strong support for coupling of
      the channels in caveolae microdomains. Further, differential expression of CAV-1
      along the CCD was apparent where CAV-1 was strongly expressed within and along
      the cell borders of kidney PC and IC, although significantly less in IC. It is
      concluded that caveolae provide a key microdomain in PC and IC for coupling of
      TRPV4 with SK3, IK1, and BK that directly contributes to TRPV4-mediated Ca2+
      signaling in these domains leading to rapid and sequential coupling of TRPV4
      SK3/IK1-BK that may play a central role in mediating Ca2+-dependent regulation of
      BK and K+ secretion.

PMID- 30207168
TI  - Enhanced Renal Ischemia-Reperfusion Injury in Aging and Diabetes.
AB  - The incidence and severity of acute kidney injury is increased in diabetic
      patients and with aging. However, the mechanisms involved have not been clearly
      established. The present study examined the effects of aging and diabetes on the
      severity of renal ischemia reperfusion (IR) injury in Sprague Dawley (SD) and
      type-2 diabetic (T2DN) rats. T2DN rats develop diabetes at 3 months of age and
      progressive proteinuria and diabetic nephropathy as they age from 6 to 18 months.
      Plasma creatinine levels after bilateral IR were significantly higher (3.4 +/-
      0.1 mg/dl) in 18-month old elderly T2DN than in middle-aged (12-month) T2DN with
      less severe diabetic nephropathy or young (3-month) and elderly (18-month)
      control SD rats (1.5 +/- 0.2, 1.8 +/- 0.1 and 1.7 +/- 0.1 mg/dl, respectively).
      Elderly T2DN rats exhibited a greater fall in medullary blood flow two hours
      following renal IR and a more severe and prolonged decline in glomerular
      filtration rate than middle-aged T2DN and young or elderly SD rats. The basal
      expression of the adhesion molecules ICAM-1 and E-selectin, and the number of
      infiltrating immune cells was higher in the kidney of elderly T2DN than age
      matched SD rats or young and middle age T2DN rats prior to renal IR. These
      results indicate that elderly T2DN rats with diabetic nephropathy are more
      susceptible to renal IR injury than diabetic animals with mild injury or age
      matched control animals. This is associated with increased expression of ICAM-1,
      E-selectin and immune cell infiltration, renal medullary vasocongestion, and more
      prolonged renal medullary ischemia.

PMID- 30207170
TI  - Adiponection, a novel player to save the kidneys.

PMID- 30207171
TI  - Podocytes contribute, and respond, to the inflammatory environment in lupus
      nephritis.
AB  - Lupus nephritis (LN) affects up to 80% of juvenile-onset systemic lupus
      erythematosus patients, leading to end-stage renal failure requiring dialysis or
      transplantation in 10-15%. Podocytes are specialised epithelial cells of the
      glomerulus known to be a key site of damage in glomerular diseases. However,
      their roles in LN have yet to be fully identified. This project aims to identify
      the structural and functional roles of podocytes in an in vitro model of LN.
      Conditionally immortalised podocytes were treated with pro-inflammatory cytokines
      (IL-1beta, TNF-alpha, IFN-alpha, IFN-gamma) alone and in combination, in an in
      vitro model of LN and were assessed for their structural and functional
      characteristics. Podocytes produce TNF-alpha, IL-6, IL-8, VEGF, GM-CSF and M-CSF
      at relatively low levels under basal conditions, stimulation with IL-1beta led to
      increased secretion of IL-6 (p=0.011), IL-8 (p=0.05), VEGF (p=0.02) and M-CSF
      (p=0.03). Stimulation with TNF-alpha led to increased secretion of M-CSF
      (p=0.049) and stimulation with IFN-gamma led to novel production of IL-10
      (p=0.036) and IP-10 (p=0.036). Podocytes demonstrate a reduction in the area
      covered by F-actin in response to IL-1beta treatment within 1h (p=0.011) that is
      restored by 24h, associated with an increase in the level of intracellular
      calcium but not with increased cell death. Podocytes contribute to the
      inflammatory milieu in LN through cytokine/chemokine secretion and also respond
      to the inflammatory milieu via rearrangement of the actin cytoskeleton leading to
      effacement, a well-known method of protection against apoptosis in these cells.
      This demonstrates that podocytes are involved in the pathogenesis of LN.

PMID- 30207169
TI  - The chemokine receptor CX3CR1 reduces renal injury in mice with angiotensin II
      induced hypertension.
AB  - The role of CX3CR1, also known as fractalkine receptor, in hypertension is
      unknown. The present study determined the role of the fractalkine receptor CX3CR1
      in hypertensive renal and cardiac injury. Expression of CX3CR1 was determined
      using CX3CR1GFP/+ mice that express a GFP reporter in CX3CR1+ cells. FACS
      analysis of leukocytes isolated from the kidney showed that 34% of CD45+ cells
      expressed CX3CR1. Dendritic cells were the majority of positive cells (67%)
      followed by macrophages (10%), NK cells (6%) and T cells (10%). Using confocal
      microscopy, the receptor was detected in the kidney only on infiltrating cells
      but not on resident renal cells. To evaluate the role of CX3CR1 in hypertensive
      end-organ injury an aggravated model of hypertension was used. Unilateral
      nephrectomy was performed followed by infusion of Ang II (1.5 ng/g/min) and a
      high salt diet in wildtype (n=15) and CX3CR1-deficient mice (n=18). CX3CR1
      deficiency reduced the number of renal dendritic cells and increased the numbers
      of renal CD11b/F4/80+ macrophages and CD11b/Ly6G+ neutrophils in Ang II infused
      mice. Surprisingly, CX3CR1-deficient mice exhibited increased albuminuria,
      glomerular injury and reduced podocyte density in spite of similar levels of
      arterial hypertension. In contrast, cardiac damage as assessed by increased heart
      weight, cardiac fibrosis and expression of fetal genes and matrix components was
      not different between both genotypes.Our findings suggest that CX3CR1 exerts
      protective properties by modulating the invasion of inflammatory cells in
      hypertensive renal injury. CX3CR1 inhibition should be avoided in hypertension
      because it may promote hypertensive renal injury.

PMID- 30207172
TI  - Aging phenotype(s) in kidneys of diabetic mice are p66ShcA dependent.
AB  - The p66ShcA protein controls cellular responses to oxidative stress, senescence
      and apoptosis. Here, we test the hypothesis that aging phenotype(s) commonly
      associated with broad category of chronic kidney disease are accelerated in
      diabetic kidneys and linked to the p66ShcA locus. At the organ level, tissue stem
      cells antagonize senescent phenotypes, by replacing old dysfunctional cells.
      Using established methods, we isolated a highly purified population of stem cell
      antigen-1 positive mesenchymal stem cells (Sca-1+ MSCs) from kidneys of Wild Type
      (WT) and p66 Knock Out (KO) mice. Cells were plated in culture media containing
      normal glucose (NG) or high glucose (HG). Reactive oxygen species (ROS)
      metabolism was substantially increased in Wild Type (WT)-MSCs in HG media in
      association with increased cell death by apoptosis and acquisition of the
      senescent phenotype. DNA microarray analysis detected striking differences in the
      expression profiles of WT and p66 KO-MSCs in HG media. Unexpectedly, the analysis
      for p66 KO-MSCs revealed upregulation of Wnt genes implicated in self renewal and
      differentiation. To test the in-vivo consequences of constitutive p66 expression
      in diabetic kidneys, we crossed Akita diabetic mouse with the p66KO mouse.
      Homozygous mutation at the p66 locus delays or prevents aging phenotype(s) in the
      kidney that may be precursors to diabetic nephropathy.

PMID- 30207173
TI  - Valsalva retinopathy associated with intranasal cocaine abuse: A case report.
AB  - INTRODUCTION: The purpose of this report is to describe a case of Valsalva
      retinopathy in an intranasal cocaine user. CASE REPORT: A 49-year-old male
      presented with a history of sudden loss of vision and inferior visual field
      defect in his left eye. Clinical evaluation of the affected eye showed best
      corrected visual acuity of 20/25 and fundus examination revealed a preretinal
      hemorrhage superior to the disk with multiple intraretinal hemorrhages in and
      around the posterior pole. On further questioning, the patient revealed
      intranasal cocaine use the day before the onset of his visual symptoms. Blood
      tests were requested to exclude blood dyscrasias or predisposition to vascular
      occlusive disorders and no further treatment measures were taken. The patient was
      reviewed a month later when his hemorrhages had completely resolved and his
      visual acuity had improved to 20/20. His blood results were within normal limits.
      CONCLUSION: Although never been reported before, Valsalva retinopathy can be
      associated with intranasal cocaine abuse and should be considered in the
      differential diagnosis of visual reduction in such population.

PMID- 30207174
TI  - Long-term results after primary intraocular lens implantation in children with
      juvenile idiopathic arthritis-associated uveitis.
AB  - PURPOSE: To evaluate the long-term outcome after cataract surgery with primary
      intraocular lens implantation in children with juvenile idiopathic arthritis
      associated uveitis. METHODS: The medical records of all 24 children (34 eyes)
      with chronic juvenile idiopathic arthritis-associated uveitis who underwent
      cataract surgery between 1990 and 2013 were reviewed retrospectively. Primary
      intraocular lens implantation was performed in all patients. RESULTS: Median age
      at diagnosis of uveitis in the first eye was 5.3 years (range: 2.7-9.4 years) and
      median age at the time of cataract surgery in the first eye was 9.7 years (range:
      4.1-16.9 years). Postoperative follow-up time ranged from 1 to 23.1 years, with a
      median of 10.9 years. Best corrected visual acuity at the last follow-up was good
      (?20/40) in 65% of the eyes. Postoperatively, glaucoma developed in 8 eyes (24%),
      posterior capsular opacification and secondary membrane formation requiring
      surgery in 15 eyes (44%), macular oedema in 5 eyes (15%) and phthisis in 2 eyes
      (6%). CONCLUSION: This study shows a favourable visual outcome in most of the
      cases. Primary intraocular lens implantation may be considered in juvenile
      idiopathic arthritis-associated uveitis complicated by cataract in patients with
      well-controlled inflammation.

PMID- 30207175
TI  - Early verbal categories and inflections in children who use speech-generating
      devices.
AB  - The use of early verbal categories, their event types, and the emergence of
      verbal inflections (-ing, -s, and -ed) were analyzed in data from four
      participants with motor speech disorders aged 9;5-13;9 (years;months) who used
      speech-generating devices to converse with a familiar adult. The study was
      conducted through a secondary analysis of a corpus of data collected as part of
      another study. It documents the production of verbs and the emergence of verb
      inflections in natural conversations between each of the participants and a
      member of their educational team over a period of up to 10 months. All
      participants used both action and state verbs, although action verbs were
      dominant. The emergence of the inflections -ing, -s, and -ed varied and were
      distributed selectively with different verb categories and event types. The
      results are discussed in terms of language development and are considered in
      terms of the findings from research with children without disabilities, which
      suggest that action verbs precede state verbs, and inflections are primarily
      acquired based on their correspondence to the verbal category (action-state).
      Implications for theory, practice, and further research are discussed.

PMID- 30207176
TI  - The tinkering m-patient: Co-constructing knowledge on how to live with type 1
      diabetes through Facebook searching and sharing and offline tinkering with self
      care.
AB  - Danish adults with type 1 diabetes value peer-to-peer interaction through the
      social media platform Facebook as a way to quickly exchange knowledge on
      essential everyday self-care for chronic illness. In this praxiographic study,
      following informants into online and offline social dimensions, I explore how
      they use Facebook to exchange self-care knowledge based on practical experiments
      and negotiations between bodies, technologies and daily lives. When in doubt
      about how to self-care on a daily basis, Danish adults with type 1 diabetes look
      to Facebook for inspiration and peer support. A synergistic process of online
      searching and sharing and offline tinkering with self-care generates person
      centred knowledge about how to live with illness that is situated to individual
      needs and unique daily lives. Facebook can be viewed as an emergent space for
      biosociality through which knowledge about how to self-care become co-constructed
      by peers based on their pragmatic experiences of self-care on a daily and ongoing
      basis.

PMID- 30207177
TI  - Potential roles of school administrators and community-residing adults in tobacco
      use prevention in Nigerian college students: a viewpoint.
AB  - Tobacco use is a key risk factor for the development of non-communicable diseases
      such as coronary heart disease, stroke, and peripheral vascular disease. On May
      31 every year, World No Tobacco Day is celebrated to draw attention to the health
      risks and other risks related to tobacco use and to campaign for effective
      policies to minimize tobacco use. In this paper, we address important issues
      related to tobacco use, and highlight the potential roles of school
      administrators and community-residing adults in supporting college students in
      Nigeria in refraining from tobacco use. We argue that various stakeholders,
      including school administrators and community-residing adults, have important
      roles to play in providing community- and school-level support to college
      students to enable them to refrain from tobacco use. However, research is needed
      to empirically measure whether and how school administrators and community
      residing adults have helped to reduce tobacco use in college students in Nigeria.

PMID- 30207178
TI  - Benefits of aged garlic extract in modulating toxicity biomarkers against p
      dimethylaminoazobenzene and phenobarbital induced liver damage in Rattus
      norvegicus.
AB  - Garlic (Allium sativum L.), a popular spice, has been used for decades in
      treating several medical conditions. Although Allicin, an active ingredient of
      garlic has been extensively studied on carcinogen-induced hepatotoxicity and
      oxidative stress in rats (Rattus norvegicus), no systematic study on the
      beneficial effects of generic aged garlic and specific aged garlic extract-Kyolic
      has been done. The present study involves rats fed chronically with two liver
      carcinogens, p-dimethylaminoazobenzene and phenobarbital, to produce
      hepatotoxicity. The aged garlic extract was characterized by UV-spectra, FTIR,
      HPLC and GC-MS. Biochemical and pathophysiological tests were performed by
      keeping suitable controls at four fixation intervals, namely, 30, 60, 90, and 120
      days, utilizing several widely accepted toxicity biomarkers. Compared to the
      controls, remarkable elevation in the activities of lactate dehydrogenase, gamma
      glutamyl transferase and decline in catalase and glucose-6-phosphate
      dehydrogenase were observed in the carcinogen fed rats. Daily administration of
      aged garlic extract, could favorably modulate the elevated levels of various
      toxicity biomarkers including serum triglyceride, creatinine, urea, bilirubin,
      blood urea nitrogen except total cholesterol. It also altered the levels of blood
      glucose, HDL-cholesterol, albumin, AST, ALT, and hemoglobin contents in
      carcinogen intoxicated rats, indicating its protective potential against
      hepatotoxicity and oxidative stress in the experimental rats. Down-regulation of
      Bcl-2 and p53 proteins caused cell cycle arrest and apoptosis in garlic fed
      group. Kyolic exhibited additional benefits by arresting cell viability of cancer
      cells. This study would thus validate the use of aged garlic extract in the
      treatment of diseases causing liver toxicity including hepatocarcinoma.

PMID- 30207179
TI  - Pazopanib in relapsed osteosarcoma patients: report on 15 cases.

PMID- 30207180
TI  - Prisoners' Personal Networks in the Months Preceding Prison: A Descriptive
      Portrayal.
AB  - This study examined personal networks of adult male prisoners ( N = 250) during a
      high-risk period prior to their incarceration. We present a descriptive portrait
      of network size, density, and relational type, and we then document the nature of
      ties within that network, focusing specifically on alters' criminal involvement,
      criminal opportunity, and reinforcement of criminal behavior. We found that
      prisoners' networks were large and dense, and that they were composed primarily
      of family and romantic partners. Most prisoners are not embedded in a personal
      network saturated with criminal influence before coming to prison. Yet, a small
      proportion are exposed to exceptionally negative influence, which, it is argued,
      may increase the risk of negative outcomes upon release if not addressed by
      evidence-based programs.

PMID- 30207182
TI  - Sodium arsenite-induced detriment of cell function in Leydig and Sertoli cells:
      the potential relation of oxidative damage and antioxidant defense system.
AB  - Arsenic is commonly found in the natural environment and is toxic agent for
      living organism in many countries in the world. Studies on animal models suggest
      that exposure to arsenic may cause reproductive toxicity; however, effect of
      arsenic on reproductive toxicity has still not been clearly described. This study
      was focused on cytotoxicity, oxidative stress, and the antioxidant defense system
      induced with exposure to sodium arsenite in Mus musculus Leydig and Sertoli
      cells. The cells were exposed to two different concentrations of sodium arsenite
      of 50 ppb (0.4 MUM) and 1000 ppb (7.7 MUM) for 24, 48, and 72 h. Following the
      exposure time, cell viability, cell proliferation, and lactate dehydrogenase
      (LDH) activity were determining using colorimetric method. Also, we evaluated
      oxidative stress markers such as glutathione (GSH), lipid peroxidation, hydroxyl
      radical, hydrogen peroxide levels, and cellular enzymatic antioxidants such as
      catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx),
      glutathione-s-transferase, and gamma-glutamyl transpeptidase (gamma-GT). As a
      result, sodium arsenite exposure in Leydig and Sertoli cells caused cellular
      cytotoxicity and downregulated the antioxidant defense system by inducing
      oxidative stress depending on concentration and time. Furthermore, this study
      demonstrated that when compared with Sertoli cells, Leydig cells were more
      affected by arsenite toxicity.

PMID- 30207183
TI  - Delivery outcomes in subsequent pregnancy following primary breech cesarean
      delivery: a retrospective cohort study.
AB  - BACKGROUND: Women may be unaware of the potential impact on subsequent deliveries
      of the decision to undergo primary breech cesarean (PBC) delivery rather than
      attempt external cephalic version (ECV). We investigated cesarean delivery rates
      and adverse maternal outcomes in the subsequent delivery following management of
      breech presentation by ECV versus PBC. METHODS: This retrospective study
      identified women who delivered subsequent to breech presentation managed by
      attempted ECV or PBC. We assessed cesarean delivery rates and adverse maternal
      outcomes including hemorrhage, placental complications, infection, and obstetric
      complications in the subsequent delivery following attempted ECV versus PBC.
      RESULTS: We identified 307 women who had attempted ECV and 508 with PBC in the
      index breech pregnancy. Following attempted ECV, 47 (15.3%) women had cesarean
      delivery in the subsequent pregnancy versus 246 (48.4%) following PBC, adjusted
      OR 0.24, 95% CI 0.16-0.35 for subsequent cesarean delivery after attempted ECV in
      the index pregnancy. The frequency of composite adverse outcomes related to
      cesarean delivery was 30 (9.8%) following attempted ECV versus 104 (20.5%) after
      PBC, p < .0001. The frequency of composite severe adverse maternal outcome was
      similar following attempted ECV 25 (8.8%) versus PBC 59 (11.9%). CONCLUSIONS: The
      current study suggests that attempted external cephalic version was associated
      with a five-fold decrease risk to undergo cesarean in the subsequent delivery and
      a significantly decreased frequency of composite adverse outcomes related to
      cesarean delivery in the subsequent delivery.

PMID- 30207184
TI  - Streptozotocin-induced leukocyte DNA damage in rats.
AB  - Although several studies using peripheral blood samples suggest that DNA damage
      is caused by streptozotocin (STZ) per se, our hypothesis is that DNA damage is
      caused by STZ-induced glycemic changes. Thus, we aimed at evaluating DNA damage
      levels in peripheral blood samples from rats at different time points within the
      first 24 h after a single intravenous dose of STZ. Female Wistar rats (control, n
      = 8; STZ, n = 7) were administered a single STZ intravenous injection (40 mg/kg
      body weight). Blood samples were collected from the tail vein for genotoxicity
      analysis by comet assay and glycemia assessment before STZ administration (time
      point zero) and at 2, 4, 6, 8, 12, and 24 h afterward. At 2 h, there was initial
      hyperglycemia associated with STZ-induced glycogenolysis that caused an increase
      in leukocyte DNA damage levels. At 4 h, glycemic and DNA damage levels were
      normalized. However, at 6 and 8 h, we observed hypoglycemia concomitant with
      increased DNA damage levels. From 10 h onward up to 24 h, DNA damage persisted
      and hyperglycemia appeared. Thus, DNA damage increased soon after both
      hypoglycemia and hyperglycemia, which were not directly induced by STZ owing to
      its known short life. In conclusion, increased peripheral blood DNA damage levels
      within 24 h after STZ administration in rats are associated with abnormal
      glycemic levels and their complications rather than with STZ per se.

PMID- 30207185
TI  - An update on the discovery and development of selective heat shock protein
      inhibitors as anti-cancer therapy.
AB  - INTRODUCTION: Over the years, not a single HSP inhibitor has progressed into the
      post-market phase of drug development despite the success recorded in various pre
      clinical and clinical studies. The inability of existing drugs to specifically
      target oncogenic HSPs has majorly accounted for these setbacks. Recent
      combinatorial strategies that incorporated computer-aided drug design (CADD)
      techniques are geared towards the development of highly specific HSP inhibitors
      with increased activities and minimal toxicities. Areas covered: In this review,
      strategic therapeutic approaches that have recently aided the development of
      selective HSP inhibitors were highlighted. Also, the significant contributions of
      CADD techniques over the years were discussed in detail. This article further
      describes promising computational paradigms and their applications towards the
      discovery of highly specific inhibitors of oncogenic HSPs. Expert opinion: The
      recent shift towards highly selective and specific HSP inhibition has shown great
      promise as evidenced by the development of paralog/isoform-selective HSP drugs.
      It could be further augmented with computer-aided drug design strategies, which
      incorporate reliable methods that would greatly enhance the design and
      optimization of novel inhibitors with improved activities and minimal toxicities.

PMID- 30207186
TI  - Informal use of restraint in nursing homes: A threat to human rights or necessary
      care to preserve residents' dignity?
AB  - Use of restraint in nursing homes is highly controversial and fundamentally
      transgresses human rights and freedom of movement and choice. While different
      forms of formal restraint use in nursing homes are broadly delineated, the use of
      informal restraint is less understood. The aim of this article is to identify
      different kinds of informal restraint, and how staff use informal restraint under
      which circumstances. This article illuminates informal restraint use based on an
      ethnographic study in four nursing homes in the Western part of Norway. We have
      identified five different forms of informal restraint use which are as follows:
      (1) diversion of residents' attention; (2) white lies; (3) persuasion and
      interpersonal pressure; (4) offers and finally (5) threats. These different forms
      of informal restraint are actions by staff against residents' will, limiting
      residents' freedom of movement and their personal preferences. In addition, we
      have identified 'grey-zone restraint' which comprises actions by staff towards
      residents which lie in-between formal and informal restraint. The use of informal
      restraint can be explained by institutional circumstances such as location,
      architecture and institutional collectivist constraints in relation to care work.
      Moreover, and paradoxically, informal restraint can be explained as a consequence
      of neo-liberal policies with establishment of extended premises for freedom of
      movement and practices of resident preferences in nursing homes. Informal
      restraint practices call into question whether these practices are compatible
      with fundamental human rights and the preservation of residents' dignity.

PMID- 30207187
TI  - Deciphering the absorption profile and interaction of multi-components of Zhi-Zi
      Da-Huang decoction based on in vitro-in silico-in vivo integrated strategy.
AB  - Zhi-Zi-Da-Huang decoction (ZZDHD) has been acknowledged with striking therapeutic
      effects for hepatobiliary disorders in the history of China. As decoctions are
      usually administrated orally, intestinal absorption, the prerequisite task of
      exerting therapeutic effects, is of utmost significance for screening potential
      active compounds and understanding the mechanism of drug action. In this work, an
      in vitro-in silico-in vivo strategy based on HPLC-DAD-ESI-TOF/MS was adopted for
      precisely profiling the intestinal absorption of ZZDHD, which integrated
      information obtained from rat everted gut sac model, octanol-water partition
      model, in silico prediction and in vivo experimental data. Besides, 34 main
      absorbed ingredients were selected as chemical markers to investigate the
      compatible interaction of the decoction on absorption level using rat everted gut
      sac experiment. In total, 106 compounds of ZZDHD were speculated as potential
      absorptive. Among them, 90 constituents predicted absorbable in at least two
      experimental models were finally recognized as intestinal absorbable ingredients.
      In addition, the absorption level of iridoids, terpenoids and flavonoid
      glycosides were found improved and the absorption of catechins and anthraquinones
      were inhibited after prescription compatibility. Taken together, this study
      presents a reliable strategy for evaluating intestinal absorption of herbal
      medicines and offers a reference for the rationality of herbal compatibility and
      the modernization of traditional Chinese medicine (TCM).

PMID- 30207188
TI  - Addendum.

PMID- 30207189
TI  - The utility of 3D-printed airway stents to improve treatment strategies for
      central airway obstructions.
AB  - Airway stents are commonly used in the management of patients suffering from
      central airway obstruction (CAO). CAO may occur directly from airway strictures,
      obstructing airway cancers, airway fistulas or tracheobronchomalacia, resulting
      from the weakening and dynamic collapse of the airway wall. Current airway stents
      are constructed from biocompatible medical-grade silicone or from a nickel
      titanium (nitinol) alloy with fixed geometry. The stents are inserted via the
      mouth during a bronchoscopic procedure. Existing stents have many shortcomings
      including the development of obstructing granulation tissue in the weeks and
      months following placement, mucous build up within the stent, and cough.
      Furthermore, airway stents are expensive and, if improperly sized for a given
      airway, may be easily dislodged (stent migration). Currently, in Australia, it is
      estimated that approximately 12,000 patients will develop CAO annually, many of
      whom will require airway stenting intervention. Of all stenting procedures, the
      rate of failure is currently reported to be at 22%. With a growing incidence of
      lung cancer prevalence globally, the need for updating airway stent technology is
      now greater than ever and personalizing stents using 3D-printing technology may
      offer the best chance of addressing many of the current limitations in stent
      design. This review article will assess what represents the gold standard in
      stent manufacture with regards to treatment of tracheobronchial CAO, the
      challenges of current airway stents, and outlines the necessity and challenges of
      incorporating 3D-printing technology into personalizing airway stents today.

PMID- 30207190
TI  - Luteolin protects microglia against rotenone-induced toxicity in a hormetic
      manner through targeting oxidative stress response, genes associated with
      Parkinson's disease and inflammatory pathways.
AB  - Rotenone, an environmental toxin, triggers Parkinson's disease (PD)-like
      pathology through microglia-mediated neuronal death. The effects and molecular
      mechanisms of flavonoid luteolin against rotenone-induced toxicity was assessed
      in microglial BV2 cells. Cells were pretreated with luteolin (1-50 uM) for 12 h
      and then was co-treated with 20 uM of rotenone for an additional 12 h in the
      presence of luteolin. The viability (MTT), IL-1beta and TNF-alpha levels and
      lactate dehydrogenase (LDH) release (ELISA), and Park2, Lrrk2, Pink1, Nrf2 and
      Trx1 mRNA levels (qRT-PCR) were measured. In rotenone exposed microglia, luteolin
      increased viability significantly at lower concentrations (1-5 uM) compared to
      higher concentrations (25-50 uM). Rotenone increased LDH release and IL-1beta
      levels in a dose-dependent manner (1-20 uM). Luteolin inhibited rotenone-induced
      LDH release, however the activity decreased in concentration-dependent manner
      Neither rotenone nor luteolin altered TNF-alpha levels, but luteolin reduced IL
      1beta levels in a concentration dependent manner in rotenone exposed cells. The
      mRNA levels of Nrf2 and Trx1, which are the master regulators of redox state,
      were increased by rotenone, as well as by luteolin, which exhibited an inverse
      relationship between its concentration and effect (1-20 uM). Park2 mRNA levels
      increased by luteolin, but decreased by rotenone. Pink1 mRNA levels was not
      altered by rotenone or luteolin. Lrrk2 mRNA levels reduced by luteolin, while it
      was increased by rotenone. Results suggest that luteolin have favorable effects
      on regulation of oxidative stress response, genes associated with PD and
      inflammatory pathways, hence protects microglia against rotenone toxicity in a
      hormetic manner.

PMID- 30207191
TI  - Oxygen therapy in acute myocardial infarctions: do we need to re-evaluate its
      necessity?

PMID- 30207192
TI  - The silver lining of greying: Ageing discourses and positioning of ageing persons
      in the field of social health insurance.
AB  - Contemporary ageing discourses and policies perceive being active as the key to a
      good later life and thereby focus on individual responsibility and self-care.
      Drawing on website articles and press releases of Belgian sickness fund agencies,
      this study analyses the ageing discourses and positioning of ageing persons of
      these organisations. A discourse analysis was performed using positioning theory
      to analyse how sickness fund agencies discursively construct the ageing process
      and position ageing persons, and to investigate how these positioning acts are
      related to sickness fund agencies' roles as social insurer, social movement,
      social entrepreneur and private insurer. Our results reveal three storylines on
      ageing; ageing as a medical problem, ageing as a new stage in life and ageing as
      a natural life process. These storylines are applied to construct ageing and
      position ageing persons in different ways. Depending on their role, sickness fund
      agencies take on a different position drawing on these different storylines. We
      also show how these storylines reproduce the moral framework on how to age well
      and thereby disempower ageing persons. Our results underline the importance of
      multidimensional perspectives on ageing.

PMID- 30207193
TI  - Chemical angioplasty for medically refractory reversible cerebral
      vasoconstriction syndrome.
AB  - PURPOSE: Medically refractory reversible cerebral vasoconstriction syndrome
      (RCVS), a rare variant of RCVS, poses a significant therapeutic challenge. Herein
      we describe a case of medically refractory RCVS that required treatment with
      intra-arterial (IA) verapamil and subsequent nimodipine, resulting in both
      angiographic and clinical improvement after failing to respond to hemodynamic
      augmentation. We also supplement a description of our case with a review of other
      case studies and case series in which IA calcium channel blockers were used to
      treat RCVS. We propose that the case we outline below demonstrates that
      neurointerventional management with IA verapamil is appropriate and effective as
      an early intervention of medically refractory RCVS. METHODS AND MATERIALS: Using
      PubMed and Google Scholar, we performed a search of the English language
      literature with several combinations of the keywords "intra-arterial", "calcium
      channel blockers", "reversible cerebral vasoconstriction syndrome", "RCVS",
      "nimodipine", "verapamil", "milrinone", and "nicardipine" to identify studies in
      which RCVS was treated with IA calcium channel blockers. RESULTS: We identified
      eight case studies and case series that met our inclusion criteria. Eighteen
      patients are encompassed in these eight studies. CONCLUSIONS: IA administration
      of calcium channel blockers has been shown to return cerebral vessels to their
      normal caliber in patients with medically refractory RCVS. However, there are no
      randomized controlled trials of the treatment of RCVS, and further studies are
      needed to elucidate the optimal treatment protocol for medically refractory RCVS.

PMID- 30207194
TI  - Protective effects of combined Losartan and Nilotinib on carbon tetrachloride
      (CCl4)-induced liver fibrosis in rats.
AB  - Tyrosine kinase inhibitors (TKIs) have been developed as therapeutic compounds
      for inhibiting the progression of liver fibrosis. In the present study, the
      simultaneous treatment of Nilotinib (TKIs) and Losartan was studied. Forty rats
      were divided into eight groups of fibrosis induced by carbon tetrachloride (CCl4)
      and therapeutics (Nilotinib, Losartan, and combination therapy). In the end,
      serum parameters of the liver and gene expression analysis of transforming growth
      factor-beta1, its receptors (TbetaRII), platelet-derived growth factor, its
      receptors (PDGFRbeta), matrix metalloproteinases (MMP-2 and MMP-9), tumor
      necrosis factor-alpha, cytochrome P450 2E1, and collagen1 type 1 were performed.
      The oxidant/antioxidant factors were also analyzed. Histopathology analysis along
      with alpha-SMA immunohistochemistry and hydroxyproline evaluation was also
      conducted for a more in-depth study. The overall results indicated a better
      therapeutic effect of co-treatment of Nilotinib-Losartan in comparison with the
      treatment of each of them alone. Interestingly, some gene and protein factors and
      fibrotic indices were reduced even to the normal levels of the control group. The
      results of this study suggest that co-administration of these two combinations,
      strengthens their anti-fibrotic properties and, due to the routine use of these
      compounds against AML and blood pressure, these compounds can be used with
      caution against human liver fibrosis.

PMID- 30207195
TI  - Using a Support-Vector Machine Algorithm to Classify Lower Extremity EMG Signals
      During Running Shod/Unshod With Different Foot Strike Patterns.
AB  - The present study aimed to use a Support Vector Machine (SVM) algorithm to
      identify and classify shod and barefoot running as well as rearfoot and forefoot
      landings. Ten habitually shod runners ran at self-selected speed. Thigh and leg
      muscle surface electromyography (EMG) were recorded. Discrete Wavelet
      transformation (DWT) and Fast Fourier transformation (FFT) were used for the
      assembly of vectors for training and classification of a SVM. Using the FFT
      coefficients for the gastrocnemius and tibialis anterior muscles presented the
      best results for differentiating between rearfoot/forefoot running in the window
      before foot-floor contact possibly due to these muscles' critical role in
      determining which part of the foot will first touch the floor. The classification
      rate was 76% and 67% respectively, with a probability of being random of 0.5% and
      4% respectively. For the same terms and conditions of classification, the DWT
      produced a reduction in the percentage of correctness of 60% and 53% with a
      probability of having reached these levels randomly of 15% and 35%. In
      conclusion, based on EMG signals, the use a FFT to train a SVM was a better
      option to differentiate running forefoot/rearfoot than to use the DWT.
      Shod/barefoot running could not be differentiated.

PMID- 30207196
TI  - Effects of age and genetic variations in VKORC1, CYP2C9 and CYP3A4 on the
      phenprocoumon dose in pediatric patients.
AB  - AIM: To study the effects of clinical and genetic factors on the phenprocoumon
      dose requirement in pediatric patients and to develop a dosing algorithm.
      METHODS: Pediatric patients who used phenprocoumon were invited to participate in
      a retrospective follow-up study. Clinical information and genotypes of genetic
      variations in CYP2C9, VKORC1, CYP4F2, CYP2C18 and CYP3A4 were collected and
      tested with linear regression for association with phenprocoumon dose
      requirement. RESULTS: Of the 41 patients included in the analysis, age, VKORC1,
      CYP2C9*2/*3 and CYP3A4*1B were statistically significantly associated with dose
      requirement, and together explained 80.4% of the variability in phenprocoumon
      dose requirement. CONCLUSION: Our study reveals that age and genetic variations
      explain a significant part of the variability in phenprocoumon dose requirement
      in pediatric patients.

PMID- 30207197
TI  - Validating Virtual Time to Contact With Home Based Technology in Young and Older
      Adults.
AB  - Virtual time to contact (VTC) is a measure of postural stability that estimates
      the virtual time it would take to reach an individual's stability boundary. This
      study aimed to validate VTC as measured by a depth sensor, and to determine if
      VTC from the depth sensor distinguishes between older adult fallers and non
      fallers compared to a force platform. VTC was assessed in 10 young and 20 older
      adults by having participants lean in a circular direction followed by five
      balance tests: eyes open, dual task, eyes open foam, eyes closed, and eyes closed
      foam. Spearman's correlations and Bland-Altman plots were conducted to determine
      validity, and Receiver Operating Curves were constructed to discriminate between
      fallers and non-fallers. Significant correlations were found in the dual task (p
      = 0.03), eyes open foam (p < 0.01), and eyes closed foam conditions (p = 0.05).
      The depth sensor discriminated between fallers and non-fallers in the eyes open
      (p = 0.02), dual task (p = 0.03), and eyes open foam conditions (p = 0.04). VTC
      was in agreement between the two devices, and VTC derived from a depth sensor and
      may be used to discriminate between older adult fallers and non-fallers during
      challenging balance conditions.

PMID- 30207198
TI  - Posterior Spinal Fusion Extended to Stable Vertebra Provides Similar Outcome in
      Juvenile Idiopathic Scoliosis Patients Compared with Adolescents with Fusion to
      the Touched Vertebra.
AB  - BACKGROUND AND AIMS: To compare outcomes between posterior spinal fusion of
      juvenile idiopathic scoliosis and adolescent idiopathic scoliosis patients with a
      minimum of 2-year follow-up. The juvenile idiopathic scoliosis patients were
      fused to the stable vertebra and adolescent idiopathic scoliosis to the touched
      vertebra. We hypothesized that extending the spinal fusion to the stable vertebra
      in juvenile patients would provide similar outcomes compared with fusion to the
      touched vertebra in adolescents. MATERIALS AND METHODS: A prospective comparative
      study of 21 consecutive children with juvenile (Risser 0) and 84 adolescent
      (Risser ?2) idiopathic scoliosis (1:4 ratio) undergoing bilateral segmental
      pedicle screw instrumentation and direct vertebral derotation with a minimum of 2
      year follow-up. RESULTS: Juvenile patients had a significantly larger main curve
      (58 degrees  vs 53 degrees , p = 0.003), more fused levels (p = 0.012) and
      posterior column osteotomies (p = 0.014) than adolescent patients. Distal adding
      on (>10 degrees ) was observed in one (4.7%) juvenile and three (3.6%) adolescent
      patients (p = 0.80), without the need for revisions. Scoliosis Research Society
      24 total score averaged 101 in juvenile and 97 in adolescent group at 2-year
      follow-up (p = 0.047). CONCLUSION: Posterior spinal fusion with bilateral
      segmental pedicle screw instrumentation to the stable vertebra provides similar
      clinical and radiographic outcomes in juvenile patients as compared with
      adolescents with fusion to the touched vertebra in idiopathic scoliosis. Health
      related quality of life as measured using the Scoliosis Research Society 24
      questionnaire at the end of follow-up was better in the juvenile as compared with
      the adolescent group.

PMID- 30207199
TI  - Genotypic characterization of Cryptosporidium species in humans and peri-domestic
      animals in Ekiti and Oyo State, Nigeria.
AB  - Cryptosporidiosis is one of the leading causes of diarrhea in humans and several
      vertebrates species. Because surveys of Cryptosporidium genotypes from animals
      and humans living in the same region are rare, our understanding of the
      importance of zoonotic transmission in the epidemiology of cryptosporidiosis
      remains superficial. PCR was used to amplify a portion of the Cryptosporidium 18S
      small subunit ribosomal RNA gene from fecal DNA from humans and livestock living
      in Ekiti and Oyo state, Nigeria. PCR-positive samples were further analyzed using
      PCR targeting the heat-shock protein HSP-70, the actin and the sporozoite
      glycoprotein gene gp60. A questionnaire was used to collect demographic
      information. Sixteen of 187 samples collected were Cryptosporidium 18S PCR
      positive. Of these, 5 samples originating from HIV-positive patients, 5 from
      otherwise healthy children, 2 from chickens, 3 from goats and 1 from a dog were
      positive for at least one marker. Sequencing of the 18S rRNA amplicons revealed
      the presence of Cryptosporidium parvum in two HIV positive patients and in a
      child; the actin sequence confirmed the presence of this species. Two samples of
      HIV-positive patients amplified C. hominis 18S rRNA, one of them confirmed by the
      HSP-70, actin and gp60 sequences. C. meleagridis was found in another HIV
      patient, while C. hominis was detected in three children (of which two were
      confirmed by gp60). C. muris was found in one child. In birds, we found C.
      meleagridis and, significantly, C. parvum, whereas we detected C. parvum and C.
      muris in one goat each. The only dog sampled was positive for Cryptosporidium
      canis. We conclude that, in the environment we surveyed, humans and animals are
      potential part of the same transmission cycle. Measures to prevent zoonotic
      transmission should therefore be considered to reduce the prevalence of
      cryptosporidiosis.

PMID- 30207200
TI  - Acetylcholine induces stem cell properties of gastric cancer cells of diffuse
      type.
AB  - Gastric cancer is the third leading cause of cancer-related death worldwide, but
      the mechanisms of gastric carcinogenesis are not completely understood. Recently,
      the role of cholinergic neuronal pathways in promoting this process has been
      demonstrated. Our aim was to extend these studies and to evaluate, using an in
      vitro model of tumorspheres, the effect of acetylcholine on human gastric cancer
      cells, and the role of acetylcholine receptors and of the nitric oxide pathway,
      in this effect. The gastric cancer cell line MKN-45 of the diffuse type of
      gastric cancer was cultured in the presence of acetylcholine, or different
      agonists or inhibitors of muscarinic and nicotinic acetylcholine receptors, or
      nitric oxide donor or inhibitor of the nitric oxide pathway, and the number and
      size of tumorspheres were assessed. The expression of cancer stem cell markers
      (CD44 and aldehyde dehydrogenase) was also evaluated by immunofluorescence and
      quantitative reverse transcription polymerase chain reaction. We showed that
      acetylcholine increased both the number and size of tumorspheres and that this
      effect was reproduced with both muscarinic and nicotinic acetylcholine receptors
      agonists and was inhibited by both receptor antagonists. The nitric oxide donor
      stimulated the tumorsphere formation, while the nitric oxide synthesis inhibitor
      inhibited the stimulatory effect of acetylcholine. Moreover, acetylcholine
      increased the expression of stem cell markers on gastric cancer cells. These
      results indicate that acetylcholine induces the stem cell properties of gastric
      cancer cells and both muscarinic and nicotinic receptors and a nitrergic pathway
      might be involved in this effect.

PMID- 30207201
TI  - Pharmacogenetic profile and major depressive and/or bipolar disorder treatment: a
      retrospective, cross-sectional study.
AB  - AIM: To compare pharmacogenetic test predictions with self-reported treatment
      experience and side effect tolerability among patients with depression taking
      psychotherapeutic medications. METHODS: Subjects completed a survey recalling
      medication effectiveness and side effects and then underwent pharmacogenetic
      testing. RESULTS: Our 15 gene pharmacogenetic panel predicted efficacy (p <
      0.001) but did not predict side effect tolerability (p = 0.70) in a group of 352
      patients. The pharmacogenetic panel and reported efficacy corresponded 60% of the
      time and medication tolerability agreed 71% of the time. CONCLUSION:
      Pharmacogenetic testing may be a useful adjunct to predict efficacy of
      medications used to treat depression.

PMID- 30207202
TI  - A 10-Year Retrospective Study of 490 Hip Fracture Patients: Reoperations, Direct
      Medical Costs, and Survival.
AB  - BACKGROUND AND AIMS: Reoperations after operative treatment of hip fracture
      patients may be associated with higher costs and inferior survival. We examined
      the acute hospital costs, long-term reoperation rates, and survival of patients
      with a new hip fracture. MATERIALS AND METHODS: A total of 490 consecutive new
      hip fracture patients treated at a single center between 31 December 2004 and 6
      December 2006 were analyzed retrospectively. Fractures were classified according
      to Garden and AO. All medical records were checked manually. The costs of
      reoperations were calculated using the diagnosis-related groups (DRG)-based
      prices. Survival analysis was performed using the life-table method. The follow
      up time was 10 years. RESULTS: In all, 70/490 patients (14.3%) needed
      reoperations. Of all reoperations, 34.2% were performed during the first month
      and 72.9% within 1 year after the primary operation. The hemiarthroplasty
      dislocation rate was 8.5%, and mechanical failures of osteosynthesis occurred in
      6.2%. Alcohol abuse was associated with a heightened risk of reoperation. The
      mean direct costs of primary fracture care were lower than the mean costs of
      reoperations (?7500 vs ?9800). The mortality rate at 10 years was 79.8% among non
      reoperated patients and 62.9% among reoperated patients. CONCLUSIONS: According
      to our hypothesis, the cost per patient of reoperation in acute care was 31%
      higher than the corresponding cost of a primary operation. Reoperations increased
      the overall immediate costs of index fractures by nearly 20%. One-third of all
      reoperations were performed during the first month and almost 75% within 1 year
      after the primary operation.

PMID- 30207203
TI  - Coordination Among Shank, Rearfoot, Midfoot and Forefoot Kinematic Movement
      During Gait in Individuals With Hallux Valgus.
AB  - An important step in the management of hallux valgus is the objective analysis of
      foot mechanics in dynamic conditions. However, the manner which hallux valgus
      affects the foot motion is poorly understood. Moreover, hallux valgus deformity
      may affect foot intersegmental coordination patterns. The purpose of this study
      was to investigate the relative motion and intersegmental foot coordination
      patterns, considering the midfoot, during gait in individuals with hallux valgus.
      Fifteen females with hallux valgus and 13 females without hallux valgus were
      recruited in this study. Three-dimensional positional data during gait were
      collected using a motion capture system and analyzed using a multisegment foot
      model and an analysis software. Intersegmental foot coordination patterns were
      assessed using a modified vector-coding technique. In individuals with hallux
      valgus, the rearfoot was significantly more everted throughout stance, and
      forefoot motion during late stance was significantly increased. In intersegmental
      coordination patterns, individuals with hallux valgus exhibited excessive
      mobility of the rearfoot relative to the midfoot segment during midstance and
      increased anti-phase motion between rearfoot and midfoot segments during late
      stance. Excessive rearfoot eversion and altered intersegmental coordination
      patterns between rearfoot and midfoot may decrease the proper rigidity of the
      foot and lead to forefoot hypermobility during late stance in individuals with
      hallux valgus.

PMID- 30207204
TI  - Cocoa beans improve mitochondrial biogenesis via PPARgamma/PGC1alpha dependent
      signalling pathway in MPP+ intoxicated human neuroblastoma cells (SH-SY5Y).
AB  - Polyphenols are shown to protect from or delay the progression of chronic
      neurodegenerative diseases. Mitochondrial dysfunction plays a key role in the
      pathogenesis of Parkinson's disease (PD). This study was aims to gain insight
      into the role of ahydroalcoholic extract of cocoa (standardised for epicatechin
      content) on mitochondrial biogenesis in MPP+ intoxicated human neuroblastoma
      cells (SHSY5Y). The effects of cocoa on PPARgamma, PGC1alpha, Nrf2 and TFAM
      protein expression and mitochondrial membrane potential were evaluated. A pre
      exposure to cocoa extract decreased reactive oxygen species formation and
      restored mitochondrial membrane potential. The cocoa extract was found to up
      regulate the expression of PPARgamma and the downstream signalling proteins
      PGC1alpha, Nrf2 and TFAM. It increased the expression of the anti-apoptotic
      protein BCl2 and increased superoxide dismutase activity. Further, the cocoa
      extract down-regulated the expression of mitochondria fission 1 (Fis1) and up
      regulated the expression of mitochondria fusion 2 (Mfn2) proteins, suggesting an
      improvement in mitochondrial functions in MPP+ intoxicated cells upon treatment
      with cocoa. Interestingly, cocoa up-regulates the expression of tyrosine
      hydroxylase, the rate limiting enzyme in dopamine synthesis. No change in the
      expression of PPARgamma on treatment with cocoa extract was observed when the
      cells were pre-treated with PPARgamma antagonist GW9662. This data suggests that
      cocoa mediates mitochondrial biogenesis via a PPARgamma/PGC1alpha dependent
      signalling pathway and also has the ability to improve dopaminergic functions by
      increasing tyrosine hydroxylase expression. Based on our data, we propose that a
      cocoa bean extract and products thereof could be used as potential nutritional
      supplements for neuroprotection in PD.

PMID- 30207205
TI  - The Implementation Gap in Laparoscopic Simulation Training.
AB  - BACKGROUND AND AIMS: Simulation-based training in laparoscopy can improve patient
      safety and efficiency of care, but it depends on how it is used. Research in
      medical education has moved from demonstrating transferability of simulation
      training to the operating room to how to best implement it. This study aims to
      investigate how simulation-based training in laparoscopy has been implemented
      Scandinavia. MATERIAL AND METHODS: An online survey was sent out to medical
      doctors at surgical, gynecological, and urological departments at 138 hospitals
      in Denmark, Norway, and Sweden. The questionnaire included questions on
      respondents' baseline characteristics, opinions, access, and actual use of
      simulation-based training in laparoscopy. RESULTS: In total, 738 respondents
      completed the survey. Of these, 636 (86.2%) of respondents agreed or strongly
      agreed that simulation-based training in laparoscopy should be mandatory. A total
      of 602 (81.6%) had access to simulation-based training in laparoscopy. Of the
      total 738 respondents, 141 (19.1%) were offered structured training courses, 129
      (17.5%) were required to reach a predefined level of competency, and 66 (8.9%)
      had mandatory courses in laparoscopy. In all, 72 (9.8%) had never used simulation
      based training in laparoscopy. CONCLUSION: An implementation gap in laparoscopic
      simulation-based training still exists in Scandinavia. Simulation equipment is
      generally available, but there is a lack of structured simulation-based training.

PMID- 30207206
TI  - Verbal cues flexibly transform spatial representations in human memory.
AB  - Humans possess a unique ability to communicate spatially-relevant information,
      yet the intersection between language and navigation remains largely unexplored.
      One possibility is that verbal cues accentuate heuristics useful for coding
      spatial layouts, yet this idea remains largely untested. We test the idea that
      verbal cues flexibly accentuate the coding of heuristics to remember spatial
      layouts via spatial boundaries or landmarks. The alternative hypothesis instead
      conceives of encoding during navigation as a step-wise process involving binding
      lower-level features, and thus subsequently formed spatial representations should
      not be modified by verbal cues. Across three experiments, we found that verbal
      cues significantly affected pointing error patterns at axes that were aligned
      with the verbally cued heuristic, suggesting that verbal cues influenced the
      heuristics employed to remember object positions. Further analyses suggested
      evidence for a hybrid model, in which boundaries were encoded more obligatorily
      than landmarks, but both were accessed flexibly with verbal instruction. These
      findings could not be accounted for by a tendency to spend more time facing the
      instructed component during navigation, ruling out an attentional-encoding
      mechanism. Our findings argue that verbal cues influence the heuristics employed
      to code environments, suggesting a mechanism for how humans use language to
      communicate navigationally-relevant information.

PMID- 30207207
TI  - Skeletal Muscle Adaptations and Passive Muscle Stiffness in Cerebral Palsy: A
      Literature Review and Conceptual Model.
AB  - This literature review focuses on the primary morphological and structural
      characteristics, and mechanical properties identified in muscles affected by
      spastic cerebral palsy (CP). CP is a non-progressive neurological disorder caused
      by brain damage and is commonly diagnosed at birth. Although the brain damage is
      not progressive, subsequent neuro-physiological developmental adaptations may
      initiate changes in muscle structure, function, and composition, causing abnormal
      muscle activity and coordination. The symptoms of CP vary among patients.
      However, muscle spasticity is commonly present and is one of the most
      debilitating effects of CP. Here, we present the current knowledge regarding the
      mechanical properties of skeletal tissue affected by spastic CP. An increase in
      sarcomere length, collagen content, and fascicle diameter, and a reduction in the
      number of satellite cells within spastic CP muscle were consistent findings in
      the literature. Studies differed, however, in changes in fascicle lengths and
      fiber diameters. We also present a conceptual mechanical model of fascicle force
      transmission that incorporates mechanisms that impact both serial and lateral
      force production, highlighting the connections between the macro and micro
      structures of muscle to assist in deducing specific mechanisms for property
      changes and reduced force production.

PMID- 30207209
TI  - Editorial.

PMID- 30207208
TI  - Generation of Linear Impulse During the Takeoff of the Long Jump.
AB  - This study investigates the effect of initial leg angle on horizontal jump
      performance. Eleven highly skilled male and female long jumpers (national and
      Olympic level) performed a series of horizontal jumps for distance. Within-jumper
      differences in initial leg angle, normalized horizontal and net vertical
      impulses, contact time, and average reaction force during the impact interval,
      post-impact interval, and in total were measured using highspeed video (240 or
      300 Hz) and a force plate (1200 Hz). Pearson correlations, Winsorized
      correlations, and the HC4 method were used to determine significant correlations
      between variables (alpha = 0.05). Within-jumper analysis indicated that when
      jumpers initiate the takeoff phase with a larger leg angle they are able to
      generate significantly greater negative horizontal and positive net vertical
      impulse (n = 7). Increased impulse generation was the result of increased contact
      time (n = 5 of 7) and / or increased average reaction force (n = 4) during the
      impact interval (n = 3) and / or post-impact interval (n = 4), depending on the
      individual. Initial leg configuration at contact and individual specific impulse
      generation strategies are important to consider when determining how an athlete
      with initial momentum can increase impulse generation to jump for distance.

PMID- 30207210
TI  - Codelivery of Doxorubicin and Verapamil for Treating Multidrug Resistant Cancer
      Cells.
AB  - BACKGROUND: Patients undergoing chemotherapy can develop resistance not only to
      the administered drug, but also to many other unrelated types of drugs, a
      phenomenon known as multidrug resistance. One of the most common mechanisms of
      multidrug resistance is an elevated expression of drug efflux pumps. Codelivery
      of an efflux pump inhibitor with a chemotherapeutic can increase the killing of
      multidrug-resistant cancer cells. OBJECTIVE: Our hypothesis was that delivering
      doxorubicin directly to the cytosol of multidrug resistant cancer cells via a
      folate-targeted liposome loaded with a perfluoropentane emulsion droplet and
      doxorubicin (folated eLipoDox), along with the delivery of verapamil to block the
      efflux pumps will prove to be more effective in killing multidrug resistant
      cancer cells compared to conventional drug delivery. METHOD: Multidrug-resistant
      KB-V1 cells and doxorubicin-sensitive KB-3-1 cells were treated with 500 uM
      verapamil and 6.5 uM doxorubicin for 2 hours. Cell viability was measured 48
      hours later via an MTT assay. RESULTS: Doxorubicin-sensitive KB-3-1 cells had a
      cell viability of 29% when treated with verapamil and folated eLipoDox, whereas
      multidrug-resistant KB-V1 cells had a cell viability of 25% (p=0.38). The co
      delivery of verapamil and folated eLipoDox produced the greatest toxicity to KB
      V1 and KB- 3-1 cells. CONCLUSION: We conclude that the cytosolic delivery of
      doxorubicin via folated eLipoDox combined with the blocking of export pumps via
      verapamil can overcome the multidrug resistance of KB-V1 cells and even
      significantly reduce the viability of doxorubicin-sensitive KB-3-1 cells.

PMID- 30207211
TI  - Targeting Nodal and Cripto-1: perspectives inside dual potential theranostic
      cancer biomarkers.
AB  - BACKGROUND: Elucidating the mechanisms of recurrence of embryonic signaling
      pathways in tumorigenesis has led to the discovery of onco-fetal players which
      have physiological roles during normal development but result aberrantly re
      activated in tumors. In this context, Nodal and Cripto-1 are recognized as onco
      developmental factors, which are absent in normal tissues but are overexpressed
      in several solid tumors where they can serve as theranostic agents. OBJECTIVE: To
      collect, review and discuss the most relevant papers related to the involvement
      of Nodal and Cripto-1 in the development, progression, recurrence and metastasis
      of several tumors where they are over-expressed, with a particular attention to
      their occurrence on the surface of the corresponding sub-populations of cancer
      stem cells (CSC). RESULTS: We have gathered, rationalized and discussed the most
      interesting findings extracted from some 370 papers related to the involvement of
      Cripto-1 and Nodal in all tumor types where they have been detected. Data
      demonstrate the clear connection between Nodal and Cripto-1 presence and their
      multiple oncogenic activities across different tumors. We have also reviewed and
      highlighted the potential of targeting Nodal, Cripto-1 and the complexes that
      they form on the surface of tumor cells, especially of CSC, as an innovative
      approach to detect and suppress tumors with molecules that block one or more
      mechanisms that they regulate. CONCLUSIONS: Overall, Nodal and Cripto-1 represent
      two innovative and effective biomarkers for developing potential theranostic anti
      tumor agents that target normal as well as CSC sub-populations and overcome both
      pharmacological resistance and tumor relapse.

PMID- 30207212
TI  - Trends in Diagnosis for Active Tuberculosis Using Nanomaterials.
AB  - BACKGROUND: Tuberculosis (TB), one of the leading causes of death worldwide, is
      difficult to diagnose based only on signs and symptoms. Methods for TB detection
      are continuously being researched to design novel effective clinical tools for
      the diagnosis of TB. OBJECTIVE: This article reviews the methods to diagnose TB
      at the latent and active stages and to recognize prospective TB diagnostic
      methods based on nanomaterials. METHOD: The current methods for TB diagnosis were
      reviewed by evaluating their advantages and disadvantages. Furthermore, the
      trends in TB detection using nanomaterials were discussed regarding their
      performance capacity for clinical diagnostic applications. RESULTS: Current
      methods such as microscopy, culture, and tuberculin skin test are still being
      employed to diagnose TB, however, a highly sensitive point of care tool without
      false results is still needed. The utilization of nanomaterials to detect the
      specific TB biomarkers with high sensitivity and specificity can provide a
      possible strategy to rapidly diagnose TB. Although it is challenging for
      nanodiagnostic platforms to be assessed in clinical trials, active TB diagnosis
      using nanomaterials is highly expected to achieve clinical significance for
      regular application. In addition, aspects and future directions in developing the
      high-efficiency tools to diagnose active TB using advanced nanomaterials are
      expounded. CONCLUSION: This review suggests that nanomaterials have high
      potential as rapid, cost-effective tools to enhance the diagnostic sensitivity
      and specificity for the accurate diagnosis, treatment, and prevention of TB.
      Hence, portable nanobiosensors can be alternative effective tests to be exploited
      globally after clinical trial execution.

PMID- 30207213
TI  - Complex Signaling Networks Controlling Dynamic Molecular Changes in Pseudomonas
      aeruginosa Biofilm.
AB  - The environment exerts strong influence on microbes. Adaptation of microbes to
      changing conditions is a dynamic process regulated by complex networks.
      Pseudomonas aeruginosa is a life-threating, versatile opportunistic and multi
      drug resistant pathogen that provides a model to investigate adaptation
      mechanisms to environmental changes. The ability of P. aeruginosa to form
      biofilms and to modify virulence in response to environmental changes are
      coordinated by various mechanisms including two-component systems (TCS), and
      secondary messengers involved in quorum sensing (QS) and c-di-GMP networks
      (diguanylate cyclase systems, DGC). In this review, we focus on the role of c-di
      GMP during biofilm formation. We describe TCS and QS signal cascades regulated by
      c-di-GMP in response to changes in the external environment. We present a complex
      signaling network dynamically changing during the transition of P. aeruginosa
      from the free-living to sessile mode of growth.

PMID- 30207214
TI  - Sulfur-containing secondary metabolites as neuroprotective agents.
AB  - Sulfur containing secondary metabolites are a relatively small group of
      substances of plant origin. The present review is focused on their
      neuroprotective properties. The results obtained in a series of in vitro and in
      vivo studies are reported. Among glucosinolates, the wide class of compounds in
      the sulfur-containing metabolites, glucoraphanin, sulforaphane and
      isothiocyanates resulted the more studied in this context and showed interesting
      properties as modulators of several systems involved in the pathogenesis of
      neurologic diseases such as oxidative stress, inflammation and apoptosis. Allium
      sativum L. (garlic) is widely known for its sulfur containing components endowed
      with health promoting activities and its medicinal properties are known from
      ancient times. In recent studies garlic components resulted active in
      neuroprotection due to the direct and indirect antioxidant properties, modulation
      of apoptosis mediators and inhibiting the formation of amyloid protein.
      Dihydroasparagusic acid, the first dimercaptanic compound isolated from a natural
      source, effectively inhibited inflammatory and oxidative processes that are
      important factors of the etiopathogenesis of neurodegenerative diseases, not only
      for its antioxidant and radical scavenging properties but also because it may
      down-regulate the expression of several microglial-derived inflammatory
      mediators. Serofendic acid represent a rare case of sulfur containing animal
      derived secondary metabolite isolated from fetal calf serum extract. It resulted
      effective in the suppression of ROS generation and in the expression of several
      inflammatory and apoptosis mediators and showed a cytotrophic property in
      astrocytes promoting the stellation process. Lastly, also the properties of
      hydrogen sulfide were reported since in recent times it has been recognized as
      signaling molecule and as a mediator in regulating neuron death or survival. It
      may be produced endogenously from cysteine but may also be released by sulfur
      containing secondary metabolites, mainly from those contained in garlic.

PMID- 30207215
TI  - Amyloid Nano-biofibrils as a New Nano-Scaffold for Lipase Immobilization.
AB  - BACKGROUND: Amyloids could be created under destabilizing conditions from various
      proteins. Having high chemical reactive groups makes the amyloid fibers suitable
      for enzyme stabilization. Imobilization of lipase as one of the stable classes of
      high catalytic power enzymes could be very valuable. OBJECTIVE: In the present
      study, the lipase from Pseudomonas cepacia was immobilized on BSA amyloid nano
      biofibrils and the kinetic parameters were compared with those of its free
      counterpart. The possibility of using this nano-material as a new nano-scaffold
      for lipase immobilization was investigated. METHOD: Response surface methodology
      was used in this study to produce the maximum amounts of amyloid fibrils using
      Design Expert 7 software. Transmission electron microscopy was employed to
      confirm the presence of amyloid fibers. The stabilization process was performed
      by glutaraldehyde mediated covalent cross-links between the enzyme and amyloid
      fibers. Kinetic parameters including activity, specific activity, optimal pH and
      temperature and thermal stability of immobilized enzyme were compared with the
      free counterpart. RESULTS: The optimum conditions for fibrillogenesis were
      obtained at 4.36 mg.ml-1 of protein after 72 hours of mild agitation in a mixed
      citrate-phosphate buffer at the pH of 4.5 and the temperature of 80 oC. The
      kinetic parameters of the immobilized lipase were improved in terms of activity,
      specific activity, Km and Vmax, optimal pH and temperature and thermal stability
      at 40 oC. Amyloid fibrils with a diameter of less than 100 nm, as a new nano
      scaffold, increased both the stability of lipase and other kinetic properties of
      the enzyme. CONCLUSION: Amyloid fibrils as a new chemically-rich nano-scaffold
      could be an appropriate matrix for lipase immobilization.

PMID- 30207217
TI  - Serum Interleukin-33 as a Biomarker in Predicting Neonatal Sepsis in Premature
      Infants.
AB  - BACKGROUND: Neonatal sepsis is considered as the most frequent cause of death in
      newborns. Early diagnosis is important to reduce mortality and morbidity. The
      rapid progression of the disease requires proper use of biomarkers specific for
      prompt diagnosis and intervention. OBJECTIVE: We aimed to evaluate the benefit of
      interleukin-33 serum levels in the diagnosis and treatment of neonatal sepsis.
      METHOD: We included 51 infants with neonatal sepsis as the main study group and
      50 neonates without sepsis as the control group. Serum levels of interleukin-6,
      interleukin-33 and C-reactive protein were measured on the 1st, 3rd and 7th days
      of sepsis in the study group and on the 3rd postpartum day in the control group,
      respectively. RESULTS: Serum levels of interleukin-6, interleukin-33 and C
      reactive protein were significantly higher in the first day of sepsis. Serum
      levels of interleukin-6, interleukin-33 and C-reactive protein decreased
      significantly on the 3rd and the 7th days of antibiotic treatment. We found a
      significant relationship between interleukin-33 and C-reactive protein and
      between interleukin-6 and C-reactive protein on the first day of sepsis.
      CONCLUSION: Serum interleukin-33 level is up-regulated in neonatal sepsis, which
      might be used as a novel diagnostic marker and also a useful tool to predict
      prognosis in early neonatal sepsis.

PMID- 30207218
TI  - The Value of Biomarkers in Optimizing the Use of Immuno-oncologic Therapy.
AB  - The development of therapies that restore or activate the host immune response -
      the socalled "immuno-oncologic" therapy - has improved the survival of some
      cancer patients harboring specific tumor types. These drugs, however, are very
      expensive which has greatly limited their use and consequently reduced the number
      of patients who could likely benefit. Not to mention, the proportion of patients
      who display a clinical benefit from therapy is limited. Thus, from a clinical and
      health economics perspective, there is a pressing need to identify and treat
      those patients for whom a given immuno- oncologic therapy is most likely to be
      beneficial. At this end, the identification, validation and use of biomarkers
      emerge as an important therapeutic tool. Here, we briefly review the state of
      immunologic biomarker development and utilization and make suggestions for
      interested clinicians, health policy makers and other stakeholders to prepare for
      the broader use of biomarkers associated with immuno-oncologic therapy in routine
      practice. The biomarker field is clearly in its earliest stages and there is no
      doubt that continued research will identify new biomarkers with valuable clinical
      indications. Of course, the clinical utility of a biomarker must consider patient
      preferences and perspectives. In addition, health economic analyses are crucial
      to better define the value of immunotherapy based on precision medicine
      strategies and promote value-based pricing.

PMID- 30207219
TI  - Cellular, Molecular and Non-Pharmacological Therapeutic Advances for the
      Treatment of Parkinson's Disease: Separating Hope from Hype.
AB  - Parkinson's Disease (PD) is a frustrating condition characterized by motor and
      nonmotor deficits majorly caused by the loss of dopaminergic cells in the
      Substantia Nigra pars compacta (SNc) and destruction of the nigrostriatal
      pathway. Despite the very respectable advances in cutting-edge approaches for the
      treatment of PD, there exist numerous challenges that have incapacitated the
      definitive treatment of this disease. This review emphasized the development of
      various non-pharmaceutical therapeutic approaches and mainly highlighted the
      cutting-edge treatments for PD including gene- and stem cell-based therapies,
      targeted delivery of neurotrophic factors, and brain stimulation techniques such
      as Transcranial Magnetic Stimulation (TMS), transcranial Direct Current
      Stimulation (tDCS), and Deep Brain Stimulation (DBS). The review covered various
      gene therapy strategies including Adeno-Associated Virus-Glutamic Acid
      Decarboxylase (AAV-GAD), AAV-Aromatic L-Amino Acid Decarboxylase (AAV-AADC),
      Lenti-AADC/Tyrosine Hydroxylase/Guanosine Triphosphate- Cyclohydrolase I (Lenti
      AADC/TH/GTP-CH1), AAV-Neurturin (AAV-NRTN), alpha-Synuclein silencing, and PRKN
      gene delivery. Also, the advantages, disadvantages, and the results of trials of
      these methods were discussed. Finally, reasons for the failure of PD treatment
      were described, with the hopes separated from hypes.

PMID- 30207220
TI  - Oncolytic Virotherapy for Breast Cancer Treatment.
AB  - Breast cancer continues to be a leading cause of mortality among women. While at
      an early stage, localized breast cancer is easily treated; however, advanced
      stages of disease continue to carry a high mortality rate. The discrepancy in
      treatment success highlights that current treatments are insufficient to treat
      advanced-stage breast cancer. As new and improved treatments have been sought,
      one therapeutic approach has gained considerable attention. Oncolytic viruses are
      uniquely capable of targeting cancer cells through intrinsic or engineered means.
      They come in many forms, mainly from four major virus groups as defined by the
      Baltimore classification system. These vectors can target and kill cancer cells,
      and even stimulate immunotherapeutic effects in patients. This review discusses
      not only individual oncolytic viruses pursued in the context of breast cancer
      treatment but also the emergence of combination therapies with current or new
      therapies, which has become a particularly promising strategy for treatment of
      breast cancer. Overall, oncolytic virotherapy is a promising strategy for
      increased treatment efficacy for advanced breast cancer and consequently provides
      a unique platform for personalized treatments in patients.

PMID- 30207221
TI  - Cancer Cell Metabolism Featuring Nrf2.
AB  - Although the major role of Nrf2 has long been established as a transcription
      factor for providing cellular protection against oxidative stress, multiple
      pieces of research and reviews now claim exactly the opposite. The dilemma - "to
      activate or inhibit" the protein requires an immediate answer, which evidently
      links cellular metabolism to the causes and purpose of cancer. Profusely growing
      cancerous cells have prolific energy requirements, which can only be fulfilled by
      modulating cellular metabolism. This review highlights the cause and effect of
      Nrf2 modulation in cancer that in turn channelize cellular metabolism, thereby
      fulfilling the energy requirements of cancer cells. The present work also
      highlights the purpose of genetic mutations in Nrf2, in relation to cellular
      metabolism in cancer cells, thus pointing out a newer approach where parallel
      mutations may be the key factor to decide whether to activate or inhibit Nrf2.

PMID- 30207222
TI  - Synthesis and biological evaluation of novel osthol derivatives as potent
      cytotoxic agents.
AB  - Natural product, osthol has been found to have important biological and
      pharmacological roles. The unmet needs in cancer therapeutics makes its
      derivatization an important and exciting field of research. Keeping this in view,
      a whole new series of diverse analogues of osthol (1) were prepared through
      modification in the lactone ring as well as in the side chain of the osthol
      molecule. All the newly synthesized compounds were subjected to anti
      proliferative screening through 3-(4,5-Dimethylthiazol-yl)-diphenyl
      tetrazoliumbromide (MTT) against four different human cancers of diverse origins
      viz. Colon (Colo-205), lung (A549), Leukemia (THP-1) and breast (MCF-7) including
      SV40 transformed normal breast epithelial cell (fR-2). Interestingly, among the
      tested molecules, most of the analogs displayed better anti-proliferative
      activity than the parent Osthol 1. However, among all the tested analogs,
      compound 28 exhibited the best results against leukemia (THP1) cancer cell line
      with IC50 of 5uM. Compound 28 induced potent apoptotic effects and G1 phase
      arrest in leukemia cancer cells (THP1). The population of apoptotic cells
      increased from 13.8% in negative control to 26.9% at 8MUM concentration of 28.
      Compound 28 also induced a remarkable decrease in mitochondrial membrane
      potential (LambdaPsim) leading to apoptosis of the cancer cells. In conclusion,
      the novel series of molecules derived from natural product osthol were
      synthesized, wherein compound 28 was found to be most effective against leukemia.
      The compound induced cancer inhibition mainly through apoptosis and thus has a
      potential in cancer therapeutics.

PMID- 30207223
TI  - Pain-prescription differences - an analysis of 500,000 discharge summaries.
AB  - BACKGROUND: Pain-relief prescriptions have led to an alarming increase in drug
      related abuse. In this study we estimate the pain reliever prescription rates at
      a major German academic hospital center and compare with the nationwide trends
      from Germany and prescription reports from the USA. METHODS: We analysed >500,000
      discharge summaries from Charite, encompassing the years 2006 to 2015, and
      extracted the medications and diagnoses from each discharge summary. Prescription
      reports from the USA and Germany were collected and compared with the trends at
      Charite to identify the frequently prescribed pain relievers and their world-wide
      utilization trends. The average costs of pain therapy were also calculated and
      compared between the three regions. RESULTS: Metamizole (dipyrone), a non-opioid
      analgesic, was the most commonly prescribed pain reliever at Charite (59%) and in
      Germany (23%) while oxycodone (29%), a semi-synthetic opioid, was most commonly
      ordered in the USA. Surprisingly, metamizole was prescribed to nearly 20% of all
      patients at Charite, a drug that has been banned for safety reasons
      (agranulocytosis) in most developed countries including Canada, United Kingdom,
      and USA. Large number of prospective cases with high risk for agranulocytosis and
      other side effects were found. Average cost of pain therapy greatly varied
      between the USA (125.3 EUR) and Charite (17.2 EUR). CONCLUSIONS: The choice of
      pain relievers is varies regionally and is often in disagreement with approved
      indications and regulatory guidelines. A pronounced East-West gradient was
      observed with metamizole use and the opposite with prescription opioids.

PMID- 30207224
TI  - Metabolomics in Vitamin Status Assessment.
AB  - The issue of vitamin deficiency persists to be a major health issue worldwide
      despite the advancements in medicine. At the same time, the effect of marginal
      vitamin deficiency status on physiological processes is proven. However, general
      methods such as immune-enzyme and fluorescence analysis, microbiological assays,
      for example, have limitations in vitamin status assessment and are not able to
      reliably reflect personal vitamin demand. The potential usefulness of modern
      metabolomics methods in vitamin status assessment is described in this review.
      These methods can be used for vitamin metabolites detection as well as for
      comprehensive metabolic phenotyping that makes them even more valuable.

PMID- 30207225
TI  - Effect of dapagliflozin on intestinal flora in MafA-deficient mice.
AB  - OBJECTIVE: To investigate the effect of dapagliflozin on intestinal microflora in
      MafA-deficient mice by establishing an animal model of diabetes. METHODS: Male
      MafA knockout mice were given intragastrically with dapagliflozin (1.0 mg/kg/d)
      for 6 weeks. Body weights and fasting blood glucose levels were measured in mice,
      and their intestinal short-chain fatty acids were measured by gas chromatography.
      At the same time, a plate count method was used to analyze the number of main
      harmful bacteria in the feces and the high-throughput sequencing was used to
      sequence the changes of intestinal flora. RESULTS: The weight of mice decreased
      after dapagliflozin gavage, the fasting blood glucose was significantly lower
      than that in the control group (P < 0.001), the contents of acetic acid and
      butyric acid in the intestinal tract of the mice increased, and the growth of
      harmful microorganisms such as Clostridium perfringens, enterococci,
      enterobacteriaceae, and intestinal enterococci were inhibited. Blautia was a
      species in the experimental group and significant different from the control and
      blank groups showed by LDA score with high-throughput sequencing. CONCLUSION:
      Dapagliflozin can reduce fasting blood glucose, decrease body weight, increase
      short-chain fatty acid content, regulate intestinal microecological balance of
      the body, and promote blood glucose and energy homeostasis.

PMID- 30207226
TI  - Pharmaceutical potentialities of beta-caryophyllene for drug delivery systems: a
      prospection.
AB  - BACKGROUND: The beta-caryophyllene (BCP), a phytocannabinoid presents in various
      essential oils, demonstrated selective action on the CB2 endocannabinoid receptor
      and attracted considerable attention because of its several pharmacological
      activities. Despite this recognized potential, this hydrophobic compound is a
      volatile and acid-sensitive sesquiterpene that readily oxidizes when exposed to
      air, and has low bioavailability in oral formulations. Thus, the development of
      formulations that guarantee its stability and increase its bioavailability is a
      challenge for its use in the pharmaceutical field. METHODS: The present review
      brings for the first time a comprehensive overview of the controlled and
      vectorized release formulations tested for BCP administration. Among these, we
      have addressed nanoemulsions, inclusion complexes with cyclodextrins, liposomes,
      wound dressings, nanocomposites and nanoparticles. A literature search was
      performed on Pubmed, Web of Science and Science direct, patents documents were
      also searched on European Patent Office, World Intellectual Property Organization
      and Brazilian National Institute of Industrial Property. RESULTS: The systems
      presented here may represent an interesting approach to overcome the limitations
      already mentioned for this terpene. These systems proved to be promising for
      improving solubility, stability and controlled release of this pharmacological
      relevant sesquiterpene. In the industrial field, some companies have filed patent
      applications for the commercial use of the BCP, however, the use of
      pharmaceutical formulations still appeared moderate. CONCLUSION: This prospective
      study evidenced the new perspectives related to BCP vectorization systems in the
      pharmaceutical and industrial marketing field and may serve as a basis for
      further research and pharmaceutical use of this powerful cannabinoid.

PMID- 30207227
TI  - Advanced Glycation End Products (AGEs), Glutathione and Breast Cancer: Factors,
      Mechanism and Therapeutic Interventions.
AB  - BACKGROUND: Advanced glycation end products (AGEs) are basically the end result
      of glycation of proteins and/or lipids in the presence of sugars. Specific cases
      of hyperglycemia have been reported with increased propensity of generation of
      AGEs. Many chronic and deadly diseases such as diabetes, cancer and
      neurodegenerative disorders have been known to be caused as a result of
      generation of AGEs. The role of glutathione (GSH) metabolism and its intricate
      association with AGEs has also been well established in breast cancer prognosis
      and treatment. To understand the etiology, mechanism and production of AGEs along
      with clinical relevance of receptors for advanced glycation end-products (RAGE)
      and RAGE ligands, and their interplay with GSH is of paramount importance
      especially in relation to breast cancer. METHOD: The available literature using
      PubMed, National Library of Medicine data base, Web of Science and SCOPUS
      indexed, Science Direct and other prestigious journals have been systematically
      reviewed using the keywords: advanced glycation end-products, breast cancer,
      glutathione RAGE, AGEs inhibitors. This narrative review of all the relevant
      papers with significant citations leads us to have greater insight into the
      action mechanism and potential therapeutic significance of AGEs inhibitors.
      RESULTS: Targeting breast cancer with the specific immunoglobulins and with other
      therapeutic interventions are needed to inhibit the generation of AGEs and manage
      glutathione expression, thus having strong implications in the management of
      breast cancer. Many RAGE ligands such as HMGB1, S100P, S100A8, S100A9 etc. have
      been known to enhance RAGE expression which may further lead to increased
      proliferation, migration and metastatic nature of tumor cells. Hence, RAGE and
      RAGE ligands in close linkup with GSH may prove to be effective therapeutic
      markers of severity of breast cancer and for angiogenesis of tumor. CONCLUSION:
      This review provides a strong platform to comprehend the etiology, mechanism and
      production of AGEs and glutathione along with the agents which can block their
      production, paving a way for the therapeutic intervention and an amicable
      solution to treat and manage breast cancer.

PMID- 30207228
TI  - Advances in BPA-induced Oxidative Stress and Related Effects and Mechanisms in
      liver,1991-2017.
AB  - Bisphenol A (BPA) is an environmental endocrine disruptor widely spreading in
      life. Its characteristics, including small does, long incubation period, and
      frequent contact, make it easy to enter human body through drinking water, food,
      air and other pathways, leading to tumors, infertility, and liver damage. The
      present review summarizes the underlying mechanism of oxidative stress and its
      related effects induced by BPA in liver. The progress of research into the
      mechanism of oxidative stress induced by BPA is summarized, including
      mitochondrial dysfunction, lipid peroxidation and inflammation reaction, liver
      dyslipidemia, apoptosis, cell death mechanism. In the future, it is necessary to
      elucidate the mechanisms and timing of BPA-induced molecular mechanisms against
      oxidative stress and epigenetic disruption, clarify the effects on different
      exposures to different genders and growth stages, the toxic effects of BPA
      surrogates, the toxic effects of BPA metabolites and BPA combined with other
      pollutants into the environment endocrine disrupting effect, to clarify the
      environmental and human health effects of BPA, to provide technical reference for
      the development of practical control measures.

PMID- 30207229
TI  - In Vitro and In Vivo Evaluation of Lidocaine Hydrochloride-loaded Injectable
      Poly(Lactic-co-glycolic Acid) Implants.
AB  - BACKGROUND: Effective postoperative pain control is essential for the recovery of
      surgical patients. However, long-term analgesia can seldom be achieved with the
      existing medications. The injectable implants prepared by biodegradable
      polyesters can be conveniently used during the surgery and slowly release
      analgesics near the operative incision for a long period. METHOD: In this study,
      we prepared lidocaine hydrochloride (Lido-HCl)-loaded injectable poly(lacticco-
      glycolic acid) (PLGA) implants for prolonged analgesia. The optimized formulation
      of this injectable implant sustained drug release for up to 5 days, with a
      cumulative release of 85.8%+/-1.9% in the in vitro release experiment. RESULTS:
      The in vivo release of the implants in rats showed good consistency with the in
      vitro release. The pharmacokinetics of Lido-HCl implants in the thigh muscle of
      rats was evaluated, and the AUC0-120 h of the Lido-HCl implant was 11.4 times
      that of Lido-HCl solution, indicating a good sustained release function of the
      implant. The pharmacodynamics of Lido-HCl implants was measured by the hot plate
      test. The Lido-HCl solution blocked the sciatic nerve of rats for less than 4 h,
      while the Lido-HCl implant efficiently blocked the nerve for approximately 120 h.
      CONCLUSION: These results demonstrated that the PLGA-based injectable implant is
      a suitable carrier for postoperative pain control.

PMID- 30207230
TI  - The Role of Lipids and Membranes in the Pathogenesis of Alzheimer's Disease: A
      Comprehensive View.
AB  - Lipids participate in Amyloid Precursor Protein (APP) trafficking and processing 
      important factors in the initiation of Alzheimer's disease (AD) pathogenesis and
      influence the formation of neurotoxic beta-amyloid (Abeta) peptides. An important
      risk factor, the presence of ApoE4 protein in AD brain cells binds the lipids to
      AD. In addition, lipid signaling pathways have a crucial role in the cellular
      homeostasis and depend on specific protein-lipid interactions. The current review
      focuses on pathological alterations of membrane lipids (cholesterol,
      glycerophospholipids, sphingolipids) and lipid metabolism in AD and provides
      insight in the current understanding of biological membranes, their lipid
      structures and functions, as well as their role as potential therapeutic targets.
      Novel methods for studying the membrane structure and lipid composition will be
      reviewed in a broad sense whereas the use of lipid biomarkers for early diagnosis
      of AD will be shortly summarized. Interactions of Abeta peptides with the cell
      membrane and different subcellular organelles are reviewed. Next, the details of
      the most important lipid signaling pathways, including the role of the plasma
      membrane as stress sensor and its therapeutic applications are given. 4-hydroxy-2
      nonenal may play a special role in the initiation of the pathogenesis of AD and
      thus the "calpain-cathepsin hypothesis" of AD is highlighted. Finally, the most
      important lipid dietary factors and their possible use and efficacy in the
      prevention of AD are discussed.

PMID- 30207231
TI  - Event-related Potentials Improve the Efficiency of Cerebrospinal Fluid Biomarkers
      for Differential Diagnosis of Alzheimer's Disease.
AB  - INTRODUCTION: The pathological process of Alzheimer's disease (AD) in the brain
      likely begins 20-30 years earlier than the emergence of its first clinical
      symptoms and symptoms of AD often overlap with the symptoms of other primary
      causes of dementia. Therefore, it is crucially important to improve early and
      differential diagnosis of the disease. Event-related potentials (ERP) measured
      non-invasively by electroencephalography have shown diagnostic potential in AD.
      AIMS: The aim of this study was to compare the efficiency of P300 and N200
      potentials and reaction time (RT) with commonly used protein biomarkers measured
      in the cerebrospinal fluid (CSF), including amyloid beta peptide (beta1-42),
      total tau (t-tau), tau protein phosphorylated at threonine 181 (p-tau181), tau
      protein phosphorylated at serine 199 (p-tau199), tau protein phosphorylated at
      threonine 231 (p-tau231), and visinin-like protein 1 (VILIP-1) in differential
      diagnosis of AD in mild cognitive impairment (MCI) and AD patients. SUBJECTS: The
      study involved 49 AD patients, 28 patients with MCI, 4 healthy control subjects
      and 16 patients with other primary causes of dementia. RESULTS: ERP (P300RT,
      N200RT, P300 counting and N200 counting) showed a moderate to strong correlation
      with protein CSF biomarkers. We confirmed previous observations of moderate to
      strong correlation between ERP and neuropsychological testing and showed that
      P300 latency and RT are shortened in AD patients on therapy with
      acetylcholinesterase inhibitors. Using ERP and RT, a predictive model for
      determination of AD likelihood in MCI patients was developed, detecting 56.3% of
      MCI patients with high risk for development of AD in our cohort. MCI patients
      with pathological levels of Abeta1-42 had prolonged P300 latency, indicating that
      a combination of ERP and CSF protein biomarkers could improve the differential
      diagnosis of AD in MCI patients. Additionally, the results suggested the
      potential of P300 latency in differentiating AD and FTD patients. CONCLUSION: Our
      data provide possible solutions for improvement of differential diagnosis of AD,
      and reveal that the diagnostic efficiency of CSF protein biomarkers t-tau, p
      tau181, p-tau199, p-tau231 and VILIP-1 could be improved by adding ERP in
      clinical practice.

PMID- 30207232
TI  - A Mesenchymal Stem Cell Line Transplantation Improves Neurological Function and
      Angiogenesis in Intraventricular Amyloid beta-Infused Rats.
AB  - BACKGROUND: Mesenchymal stem cell transplantation is demonstrated to improve
      neurological performance in neurodegenerative diseases including Alzheimer's
      disease. OBJECTIVE: The objective of this study is to understand the underlying
      mechanism of such improvement. METHODS: Amyloid beta (Abeta) peptide was infused
      into the lateral ventricle of adult Wister rats using the osmotic pump. After 15
      days of continuous infusion, a mesenchymal stem cell line (B10) was transplanted
      in the lateral ventricle. Learning-related behavior was evaluated by 2-way
      shuttle avoidance test. Fifteen days after B10 transplantation, pathological and
      expressional changes were evaluated. RESULTS: Compared to sham group, learning
      related behavior was significantly decreased in Abeta-infused non-transplanted
      group, but not in B10-transplanted group. Nissl staining results demonstrated
      that the number of hippocampal pyramidal neurons in CA1 area in B10-transplanted
      group was similar to the sham group, whereas that was decreased in Abeta-infused
      non-transplanted group. Abeta mainly deposited in the vessels of the brains of
      Abeta-infused non-transplanted rats, which was decreased by B10 transplantation.
      Moreover, B10 transplantation increased vessel density as well as endoglin
      positive cells. The number of astrocyte and microglia was decreased in Abeta
      infused non-transplanted group, which was returned to the level of sham animals
      by B10 transplantation. Real-time PCR and immunostaining results showed that B10
      transplantation significantly increased IL-1beta mRNA and protein expression.
      CONCLUSION: Thus, our result showed that MSC transplantation effectively
      decreased Abeta deposition in the cerebral vessel and increased angiogenesis,
      which could be a possible cause of improved neurological performance in Abeta
      infused AD model rats.

PMID- 30207233
TI  - Mapping Exchangeable Protons to Monitor Protein Alterations in the Brain of an
      Alzheimer's Disease Mouse Model by Using MRI.
AB  - OBJECTIVE: The study aimed to investigate exchangeable proton signals of Abeta
      proteins of the brains of Alzheimer's disease (AD) model mice by using a chemical
      exchange-sensitive spin-lock (CESL) MR imaging technique. METHOD: Eight non
      transgenic (Tg) mice (5 young and 3 old) and twelve Tg-APPswe/PSdE9 mice (5 young
      and 7 old) were used in this study. CESL Z-spectra were obtained by using two
      saturation powers, which were omega1 = 25 Hz with TSL = 3.0 s and omega1 = 500 Hz
      with TSL = 150 ms, at 71 offsets with uneven intervals between the offset
      frequencies at Omega = +/-7.0 ppm at a 9.4-T animal MRI system. For Zspectrum
      analyses, regions of interest (ROIs) were drawn in the cortex, hippocampus, and
      thalamus of both hemispheres. Magnetization transfer ratio asymmetry (MTRasym)
      curves were obtained from the Zspectra. The Mann-Whitney test was used to compare
      the MTRasym values between the Tg and non-Tg mice for each offset frequency and
      for each ROI. RESULTS: The water saturation width of the full Z-spectrum was
      narrow with the 25-Hz saturation power, but relatively broad with the 500-Hz
      saturation power. With the 25-Hz CESL saturation power, most of the MTRasym
      values were negative for 3.5-, 3.0-, 2.0-, and 0.9-ppm offset frequencies and the
      MTRasym values were significantly different between the control and Tg groups
      only in the left thalamus region at 3.5 ppm offset (p=0.0487). The MTRasym values
      were -6% to -7% for both 3.5 and 3.0 ppm, but less than -2% for both 2.0 and 0.9
      ppm. With 500-Hz CESL saturation power, all the MTRasym values were positive for
      the 3.5-, 3.0-, 2.0-, and 0.9-ppm offset frequencies and the MTRasym values were
      not significantly different between the control and Tg groups at all ROIs and at
      all offset frequencies. However, a trend towards a significant difference was
      observed between the control and Tg groups in the right cortex at 3.5 ppm
      (p=0.0578). The MTRasym values were 6% to 9% for 3.5, 3.0, and 2.0 ppm, but less
      than 2% for 0.9 ppm. CONCLUSION: In an in-vivo AD model experiment, MTRasym
      values increased with the high saturation power than with the low saturation
      power. The MTRasym values were not significantly different, except in the left
      thalamus region at 3.5 ppm offset. The CESL technique should be further developed
      to enable its application in the brain of patients with neurodegenerative
      diseases.

PMID- 30207234
TI  - Neuroprotective Strategies for Neurological Disorders by Natural Products: An
      update.
AB  - Nature has bestowed mankind with surplus resources (natural products) on land and
      water. Natural products have significant role in prevention of disease and
      boosting of health in humans and animals. These natural products have been
      experimentally documented to possess various biological properties such as
      antioxidant, anti-inflammatory and anti-apoptotic activities. In vitro and in
      vivo studies have further established the usefulness of natural products in
      various preclinical models of neurodegenerative disorders. Natural products
      include phytoconstituents, like polyphenolic antioxidants, found in herbs,
      fruits, nuts, vegetables and also in marine and fresh water flora. These
      phytoconstituents may potentially suppress neurodegeneration and improve memory
      as well as cognitive functions of the brain. Also, they are known to play a
      pivotal role in prevention and cure of different neurodegenerative diseases, such
      as Alzheimer's disease, epilepsy, Parkinson's disease and other neuronal
      disorders. The large scale neuro-pharmacological activities of natural products
      have been documented which is due to be the result of either inhibition of
      inflammatory processes, or the up-regulation of various cell survival proteins or
      combination of both. Due to the scarcity of human studies on neuroprotective
      effects of natural products, this review focuses on the various established
      activities of natural products in in vitro and in vivo preclinical models, and
      their potential neuro-therapeutic applications using the available knowledge in
      the literature.

PMID- 30207235
TI  - Astragaloside IV supplementation promotes a neuroprotective effect in
      experimental models of neurological disorders: a systematic review.
AB  - BACKGROUND: Neurological disorders constitute a growing worldwide concern due to
      the progressive aging of the population and the risky behavior they represent.
      Herbal medicines have scientific relevance in the treatment of these pathologies.
      One of these substances, Astragaloside IV (AS-IV), is the main active compound
      present in the root of Astragalus membranaceus (Fisch.) Bge, a Chinese medicinal
      herb with neuroprotective properties. </p> <p> Objective: In the present study we
      performed a systematic review that sought to comprehend the neuroprotective
      effect presented by AS-IV in experimental models of neurological disorders. </p>
      <p> Method: This study is a systematic review, where an electronic search in
      United States National Library of Medicine (PubMed), Science Direct, Cochrane
      Library, Scientific Electronic Library Online (SciELO), Scopus, Web of Science,
      Medline via Proquest and Periodicos Capes databases covering the years between
      2007 and 2017, using "Astragaloside IV" and "Neurodegenerative diseases";
      "Astragaloside IV" and " Neurological disorders" as reference terms. </p> <p>
      Results: A total of 16 articles were identified, in which the efficacy of AS-IV
      was described in experimental models of Parkinson's disease, Alzheimer's disease,
      cerebral ischemia and autoimmune encephalomyelitis, by improving motor deficits
      and/or neurochemical activity, especially antioxidant systems, reducing
      inflammation and oxidative stress. </p> <p> Conclusion: The findings of the
      present study indicate that the administration of AS-IV can improve behavioral
      and neurochemical deficits largely due to its antioxidant, antiapoptotic and anti
      inflammatory properties, emerging as an alternative therapeutic approach for the
      treatment of neurological disorders.

PMID- 30207236
TI  - Traumatic Brain Injury altered Normal Brain Signaling Pathways: Implications for
      Novel Therapeutics approaches.
AB  - Traumatic brain injury (TBI) is the main reason of lifelong disability and
      casualty worldwide. In the United state alone, 1.7 million traumatic events occur
      yearly, out of which 50,000 results in deaths. Injury to the brain could alter
      various biological signaling pathways such as excitotoxicity, ionic imbalance,
      oxidative stress, inflammation, and apoptosis which can result in various
      neurological disorders such as Psychosis, Depression, Alzheimer disease,
      Parkinson disease, etc. In literature, various reports have indicated the
      alteration of these pathways after traumatic brain injury but the exact mechanism
      is still unclear. Thus, in the first part of this article, we have tried to
      summarize TBI as a modulator of various neuronal signaling pathways. Currently,
      very few drugs are available in the market for the treatment of TBI and these
      drugs only provide the supportive care. Thus, in the second part of the article,
      based on TBI altered signaling pathways, we have tried to find out potential
      targets and promising therapeutic approaches in the treatment of TBI.

PMID- 30207237
TI  - Association of PPARG gene polymorphisms Pro12Ala with type 2 diabetes mellitus: A
      meta-analysis.
AB  - BACKGROUND: Previous studies suggested that the single nucleotide polymorphisms
      of Pro12Ala located within the PPARG gene were significantly associated with the
      T2DM. Recently, the genetic studies on Pro12Ala were conducted in the different
      ethnic groups and the results of each study were shown to be inconsistent.
      Moreover, the systematic review has not been updated since 2000. OBJECTIVE: To
      further validate the risk of Pro12Ala for T2DM disease based on the genetic data.
      METHODS: The genetic studies on the Pro12Ala in the T2DM were searched in the
      PubMed and PMC database from January 2000 to October 2017. The meta-analysis was
      conducted with the CMA software. RESULTS: The meta-analysis collected 14 studies
      including 20702 cases and 36227 controls. The combined analysis of all studies
      found that Pro12Ala was shown to be significantly associated with T2DM and the
      Ala allele played the increasing risks for the disease. Nevertheless, publication
      bias was detected in the combined analysis. The subgroup analysis indicated that
      Pro12Ala was still shown significant in the Caucasian and Chinese population.
      There was no heterogeneity and publication bias in these two groups, Conclusion:
      The meta-analysis confirmed the evidence that the Pro12Ala was the susceptible
      variant for the decreasing risks for the T2DM.

PMID- 30207238
TI  - Ligand-Based Drug Design: Synthesis and Biological Evaluation of Substituted
      Benzoin Derivatives as Potential Antitumor Agents.
AB  - BACKGROUND: Phosphoinositide 3-kinase alpha (PI3Kalpha) has emerged as a
      promising target for anticancer drug design. OBJECTIVES: Target compounds were
      designed to investigate the effect of the p-OCH3 motifs on ligand/PI3Kalpha
      complex interaction and antiproliferative activity. METHODS: Synthesis of the
      proposed compounds, biological examination tests against human colon
      adenocarcinoma (HCT-116), breast adenocarcinoma (MCF-7), and breast carcinoma
      (T47D) cell lines, along with Glide docking studies. RESULTS: A series of 1,2
      bis(4-methoxyphenyl)-2-oxoethyl benzoates was synthesized and characterized by
      means of FT-IR, 1H and 13C NMR, and by elemental analysis. Biological
      investigation demonstrated that the newly synthesized compounds exhibit
      antiproliferative activity in human colon adenocarcinoma (HCT-116), breast
      adenocarcinoma (MCF-7), and breast carcinoma (T47D) cell lines possibly via
      inhibition of PI3Kalpha and estrogen receptor alpha (ERalpha). Additionally,
      results revealed that these compounds exert selective inhibitory activity, induce
      apoptosis, and suppress VEGF production. Compound 3c exhibited promising
      antiproliferative activity in HCT-116 interrogating that hydrogen bond-acceptor
      mediates ligand/PI3Kalpha complex formation on m- position. Compounds 3e and 3i
      displayed high inhibitory activity in MCF-7 and T47D implying a wide cleft
      discloses the o-attachment. Furthermore, compound 3g exerted selective inhibitory
      activity against T47D. Glide docking studies against PI3Kalpha and ERalpha
      demonstrated that the series accommodate binding to PI3Kalpha and/or ERalpha.
      CONCLUSION: The series exhibited a potential antitumor activity in human
      carcinoma cell lines encoding PI3Kalpha and/or ERalpha.

PMID- 30207239
TI  - ZnO Nanoparticles catalyst in Synthesis of Bioactive Fused Pyrimidines as Anti
      breast Cancer Agents Targeting VEGFR-2.
AB  - BACKGROUND: Pyrimidines emerged as a remarkable class of heterocyclic compounds
      that have reinforced the pharmaceutical chemistry with various bioactive
      antitumor agents. Moreover, pyrimidine scaffold displayed VEGFR-2 inhibitory
      activity. Also, nano-sized catalysts are used in organic reactions in order to
      speed up the catalytic process. OBJECTIVE: we interested herein to synthesize a
      new series of fused pyrimidines using ZnO(NPs) to investigate their antitumor
      efficiency against breast MCF7 cancer and their VEGFR-2 inhibition properties .
      METHOD: A simple and efficient method for the synthesis of fused pyrimidines was
      developed using zinc oxide nanoparticles ZnO(NPs) in refluxing ethanol. RESULTS:
      The purposed structures of all new fused pyrimidines are in agreement with their
      spectral data. Antitumor evaluation of newly fused pyrimidine derivatives against
      breast MCF-7 cancer was performed. It was apparent that the 2-phenylpyrazolo[1,5
      a]pyrimidine derivatives 9a (IC50 = 9.12+/-1.16 ug/ml), 9c (IC50 = 9.10+/-1.07
      ug/ml) and 9d (IC50 = 9.60+/-1.22 ug/ml) exhibited equipotent antitumor activity
      as Tamoxifen (IC50 = 9.11+/-0.90 ug/ml). Also, the inhibitory activity of the
      novel fused pyrimidine derivatives on VEGFR-2 as well as Tamoxifen was determined
      using breast cancer cell line MCF-7. The data was obvious that 2
      phenylpyrazolo[1,5-a]pyrimidine derivatives 9a, 9c and 9d exhibited noticeable
      VEGFR-2 inhibitory effect with % inhibition ranging from 80-84 % versus Tamoxifen
      93.5%. CONCLUSION: We succeeded in this context to synthesize new fused
      pyrimidines using ZnO(NPs) as anti-breast cancer agents targeting VEGFR-2 .

PMID- 30207240
TI  - Synthesis, molecular modeling and biological evaluation of 5-arylidene-N,N
      diethylthiobarbiturates as potential alpha-glucosidase inhibitors.
AB  - BACKGROUND Barbituric acid derivatives are a versatile group of compounds which
      are identified as potential pharmacophores for the treatment of anxiety, epilepsy
      and other psychiatric disorders. They are also used as anesthetics and have sound
      effects on the motor and sensory functions. Barbiturates are malonylurea
      derivatives with a variety of substituents at C-5 position showing resemblance
      with nitrogen and sulfur containing compounds like thiouracil which exhibited
      potent anticancer and antiviral activities. Recently, barbituric acid derivatives
      have also received great interest for applications in nanoscience. OBJECTIVE
      Synthesis of 5-arylidene-N,N-diethylthiobarbiturates, biological evaluation as
      potential alpha-glucosidase inhibitors and molecular modeling. METHODS In the
      present study, N,N-Diethylthiobarbituric acid derivatives were synthesized by
      refluxing of N,N-diethylthiobarbituric acid and different aromatic aldehydes in
      distilled water. In a typical reaction; a mixture of N,N-diethylthiobarbituric
      acid 0.20 g (1 mmol) and 5-bromo-2-hydroxybenzaldehyde 0.199 g (1 mmol) mixed in
      10 mL distilled water and reflux for 30 minutes. After completion of the
      reaction, the corresponding product 1 was filtered and dried and yield
      calculated. It was crystallized from ethanol. The structures of synthesized
      compounds 1-25 were carried out by using 1H, 13C NMR, EI spectroscopy and CHN
      analysis were used for the determination of their structures. The alpha
      glucosidase inhibition assay was performed as given by Chapdelaine et al., with
      slight modifications and optimization. RESULTS Our newly synthesized compounds
      showed a varying degree of alpha-glucosidase inhibition and at least four of them
      were found as potent inhibitors. Compounds 6, 5, 17, 11 exhibited IC50 values
      (Mean+/-SEM) of 0.0006 +/- 0.0002, 18.91 +/- 0.005, 19.18 +/- 0.002, 36.91 +/-
      0.003 &mu;M, respectively, as compared to standard acarbose (IC50, 38.25 +/- 0.12
      &mu;M). CONCLUSION Our present study has shown that Compunds 6, 5, 17, 11
      exhibited IC50 values of 0.0006 +/- 0.0002, 18.91 +/- 0.005, 19.18 +/- 0.002,
      36.91 +/- 0.003 &mu;M, respectively. The studies were supported by in silico data
      analysis.

PMID- 30207241
TI  - Anticancer Activity and Topoisomerase II Inhibition of Naphthalimides with omega
      Hydroxylalkylamine Side-Chains of Different Lengths.
AB  - 1,8-Naphthalimides (benzo[de]isoquinoline-1,3-diones) modified in various
      positions of chromophore, provided an effective method for enhancing their
      anticancer activity and reducing undesirable toxic effects. To accomplish this
      goal, several new 6- and 6,7-substitued 1,8-naphthalimides containing a omega
      hydroxylalkylamine side-chains of different length were obtained and evaluated in
      the report presented. Upon examination, it appeared that the replacement of the
      nitro groups in the chromophore slightly reduce its anticancer activities,
      whereas the presence of both nitro groups and omega-hydroxylalkylamine chain
      resulted in seriously increased anticancer activities. Obtained compounds showed
      Topo II inhibitory activity, moreover, influence of the substitution pattern on
      the ability to inhibit Topo II activity and cancer cells proliferation was
      observed.

PMID- 30207242
TI  - A mini-review: the therapeutic potential of mesenchymal stem cells and relevant
      signaling factors.
AB  - Mesenchymal stem cells (MSCs), with its capacity of multi-directional
      differentiation, low immunogenicity and high portability, which made BMSCs serve
      as ideal "seed cells" in ophthalmological disease therapy. Therefore, in this
      mini-review we examined recent literature concerning the potential application of
      MSCs for the treatment of ophthalmological disease, which including : activity of
      transplanted cells, migration and homing of MSCs, immuno-modulatory and anti
      inflammatory effects of MSCs and signaling involved. Each aspect is complementary
      to the others and together these aspects promoted further understanding for the
      potential use of MSCs in treating ophthalmological diseases.

PMID- 30207243
TI  - CellSaic, a Cell Aggregate-like Technology Using Recombinant Peptide Pieces for
      MSC Transplantation.
AB  - In the field of stem cell therapy, research on the application of mesenchymal
      stem cells (MSCs) has flourished because of the various functions. On the other
      hand, research on the method of cell transplantation has developed from the
      administration of cell suspensions to cell-sheet engineering and 3D technology.
      In the trend, a cell transplantation platform named CellSaic, which is a
      combination of xeno-free recombinant scaffolds in a cell aggregate-like shape,
      was developed. CellSaic is the cell transplantation platform that can prevent the
      central necrosis within cell aggregates by arranging the cells and petaloid
      pieces of recombinant peptide (RCP) in a mosaic. The prevention of central
      necrosis is the most significant advantage over other 3D culture systems. This
      review details the unique characteristics of CellSaic including safety
      examination results and describes its future application for MSC transplantation.
      Particularly, in the application of MSCs, it has been reported that the MSC
      CellSaics increased the effect on improving various symptoms compared with MSCs
      only in the application of the therapy to inflammatory bowel disease (IBD),
      cerebral infarction, bone cartilage regeneration in joints, and islet
      transplantation. In accordance with the "One Health" concept, it is anticipated
      that this technology is expected to contribute to companion animal therapy and
      human therapy in the future.

PMID- 30207244
TI  - Chitosan in Biomedical Engineering: A Critical Review.
AB  - Biomedical engineering seeks to enhance the quality of life by developing
      advanced materials and technologies. Chitosan-based biomaterials have attracted
      significant attention because of having unique chemical structures with desired
      biocompatibility and biodegradability, which play different roles in membranes,
      sponges and scaffolds, along with bring about promising biological properties
      such as biocompatibility, biodegradability and non-toxicity. Therefore, chitosan
      derivatives have been widely used in a vast variety of uses, chiefly
      pharmaceuticals and biomedical engineering. It is attempted here to draw a
      comprehensive overview of chitosan emerging applications in medicine, tissue
      engineering, drug delivery, gene therapy, cancer therapy, ophthalmology,
      dentistry, bio-imaging, bio-sensing and diagnosis. The use of stem cells (SCs)
      has given an interesting feature to the use of chitosan, so that regenerative
      medicine and therapeutic methods have benefited from chitosan-based platforms.
      Plenty of the most recent discussions with stimulating ideas in this field are
      covered that could hopefully serve as hints for more developed works in
      biomedical engineering.

PMID- 30207245
TI  - Mesenchymal stromal cells and natural killer cells: a complex story of love and
      hate.
AB  - Mesenchymal stromal cells (MSCs), characterized by both multidifferentiation
      potential and potent immunomodulatory capacity, represent a promising, safe and
      powerful cell based-therapy for repairing tissue damage and/or treating diseases
      associated with aberrant immune responses. Natural killer (NK) cells are granular
      lymphocytes of the innate immune system that function alone or in combination
      with other immune cells to combat both tumors and virally infected cells. After
      their infusion, MSCs are guided by host inflammatory elements and can interact
      with different immune cells, particularly those of the innate immune system.
      Although some breakthroughs have been achieved in understanding these
      interactions, much remains to be determined. In this review, we discuss the
      complex interactions between NK cells and MSCs, particularly the importance of
      improving the therapeutic value of MSCs.

PMID- 30207246
TI  - A review on the role of VEGF in Tamoxifen resistance.
AB  - Molecular deviations can contribute to the development of breast cancer. For
      instance, estrogen and estrogen receptors play a significant role in inducing
      tumor proliferation. However, the efficacy of endocrine therapy through
      administration of anti-estrogen drugs, such as Tamoxifen, is challenged by
      acquired resistance. Tamoxifen resistance occurs as a consequence of signaling
      pathways over-activated within this intricate network. Since angiogenesis is
      vital to tumor growth due to the essential nutrients it provides, it has been
      shown that microvessel count was greater in Tamoxifen resistant tissues than in
      responsive ones. Analyzing the molecular network involved in Tamoxifen resistance
      in breast cancer patients has depicted that the pathway triggered by vascular
      endothelial growth factor (VEGF) not only can cause angiogenesis, but can also
      facilitate proliferation of cancer cells. In this review, the interaction between
      estrogen, Tamoxifen, VEGF, and VEGFRs in Tamoxifen resistant cells has been
      discussed.

PMID- 30207247
TI  - Computational Studies in Drug Design against Cancer.
AB  - BACKGROUND: The application of in silico tools in the development of anti cancer
      drugs. </p> <p> Objective: The summing of different computer aided drug design
      approaches that have been applied in the development of anti cancer drugs. </p>
      <p> Method: Structure based, ligand based, hybrid protein-ligand pharmacophore
      methods, Homology modeling, molecular docking aids in different steps of drug
      discovery pipeline with considerable saving in time and expenditure. In silico
      tools also finds applications in the domain of cancer drug development. </p> <p>
      Results: Structure-based pharmacophore modeling aided in the identification of
      PUMA inhibitors, structure based approach with high throughput screening for the
      development of Bcl-2 inhibitors, to derive the most relevant protein-protein
      interactions, anti mitotic agents; I-Kappa-B Kinase beta (IKK- beta) inhibitor,
      screening of new class of aromatase inhibitors that can be important targets in
      cancer therapy. </p> <p> Conclusion: Application of computational methods in the
      design of anti cancer drugs was found to be effective.

PMID- 30207248
TI  - Alarming and threatening signals from health centers about multi drug resistance
      Staphylococcus haemolyticus.
AB  - OBJECTIVES: Nowadays, due to the biofilm formation among of coagulase-negative
      staphylococci (CoNS), acquisition of antibiotic resistance and virulence genes
      could be noted. These organisms resembling other staphylococcus have mecA gene
      which encoded methicillin resistance but the diversity of it among CoNS is higher
      than other species. Based on increasing of antibiotic resistance in
      Staphylococcus haemolyticus, analyzing of phenotypic and genotypic biofilm
      formation, antibiotic resistance and genes involved in this process, SCCmec and
      ACME typing were placed as aims of current study. </p> <p> Methods. The number of
      256 clinical CoNS isolates were collected which 49 isolates were identified as S.
      haemolyticus. For evaluation antibiotic resistance disk agar diffusion methods
      was applied, also biofilm assay carried out among methicillin resistance S.
      haemolyticus and SCCmec and ACME typing was performed.</p> <p> Results. The
      results of antibiotic susceptibility indicated that the highest resistance
      belongs to cotrimoxazole and erythromycin (86.6%) and the frequency of blaA
      (96.5%) and msrA (79.3%) genes were much higher than others. Among MRSH isolates
      58.6 % have weak biofilm phenotype and 41.4% showed a moderate biofilm density.
      Also among of biofilm correlated genes, IS 256 (79.31%) was the most frequent.
      The SCCmec typing of MRSH isolates indicated that the type V was dominant.</p>
      <p> Conclusions. Our finding indicated that correlation is between high rates of
      existence Is 256 gene and high prevalence of weak biofilm phenotype among MRSH
      isolates. Current study revealed that the multiple antibiotic resistances among
      clinical S. haemolyticus isolates are increasing and this is a warning to public
      health.

PMID- 30207249
TI  - Nocardiosis in Sudan: Current Situation and Future Perspective.
AB  - BACKGROUND: Infections caused by nocardiae are rare, but misguided to clinicians,
      especially if there is a delay in the diagnosis and/or low response to
      chemotherapy. The incidence of nocardiosis is increasing constantly worldwide,
      and the situation is getting worse if we consider immunocompromised individuals,
      such as HIV positive patients since they are at higher risk. Surgical amputation,
      although not common, but should be considered as a result in some cases that
      cause partial disability. AIMS: To throw light on the situation of nocardiosis in
      Sudan, investigate the possible reasons for the increased prevalence and discuss
      the possible strategies for prevention and control. Data Review: PubMed
      investigations were adopted using terms that included nocardiosis in Sudan as
      well as in other parts of the world. Part of the review has been retrieved from
      main library of the post graduate college, University of Khartoum and University
      of Newcastle upon Tyne. FINDINGS: In Sudan, nocardiosis revealed wide
      geographical distribution; different cases were reported from western, middle as
      well as the northern parts of the country. Moreover, several clinical
      presentations were seen. While pulmonary, coetaneous and subcutaneous infections
      represent the primary types caused by nocardia, disseminated infection in two or
      more organs had also been reported. As in all other infectious diseases,
      opportunistic nocardiosis is more prevalent among HIV patients. Zoonotic
      transmission of the disease was also proved; several cases of bovine and caprine
      mastitis were due to one or another species of nocardia. The effect of ecology on
      the prevalence and pathogenicity of Nocardia is proved by the isolation of
      nocardia and other actinomycetes from Sudanese soil, which represents the most
      probable source of infection. Regarding treatment, effective results are usually
      obtained by the use of sulfonamides and third generation cephalosporins. However,
      surgical interference is also used when necessary, such as in cases of drainage
      of abscesses. CONCLUSION: Since the description of Nocardia by Edmond Nocard in
      1888, it started to be well known worldwide, In Sudan, however, the awareness
      regarding this bacteria is still below the level, and is only due to the end of
      the fifty.

PMID- 30207250
TI  - Sofosbuvir, pegylated interferon and ribavirin in treatment of an Egyptian cohort
      with hepatitis C virus infection in real life clinical practice.
AB  - BACKGROUND & AIMS: Hepatitis C virus infection is a major public health problem
      in Egypt with a risk for morbidity and mortality due to chronic liver disease
      complications. Worldwide, Egypt has the highest prevalence of HCV infection with
      the overall prevalence about 14.7%. The aim of this study was to evaluate the
      antiviral efficacy, safety, and tolerability of sofosbuvir (SOF) plus pegylated
      interferon and ribavirin (RBV) in Egyptian patients with chronic hepatitis C
      virus (HCV) infection. METHODS: This study was carried out on 1200 patients with
      chronic hepatitis C virus infection who were eligible for interferon therapy.
      They were treated with the triple therapy of sofosbuvir 400 mg once daily, Peg
      INF subcutaneous injection weekly for 12 weeks in combination with oral weight
      based ribavirin. The primary outcome measures were the number of patients with
      successful eradication of the virus evidenced by sustained virologic response
      (SVR) at 12 Weeks After discontinuation of Therapy (SVR12) and the secondary
      outcome measures were the incidence of adverse effects associated with the tested
      HCV therapy. RESULTS: The mean age of the patients was 49.32.

PMID- 30207251
TI  - Thyroid Function 'in Egyptian Children with Sickle Cell Anemia in correlation
      with iron' load.
AB  - BACKGROUND: 'Sickle cell disease (SCD) is characterized by defective hemoglobin
      synthesis, hemolytic anemia, frequent thrombosis and chronic organ damage
      including endocrine organs'. AIM OF THE WORK: to assess thyroid function in
      children with SCD in correlation with iron load. PATIENTS AND METHODS: This study
      was conducted on 40 children with SCD with iron overload (serum ferritin more
      than 1000 ng/ml) including 22 males and 18 females with their ages ranging from
      11-14 years and mean age value of 11.63+/-1.36 years and 40 healthy children of
      matched age and sex as a control group. 'For all patients; complete blood count,
      hemoglobin electrophoresis, serum ferritin, serum iron, iron binding capacity'
      and thyroid function including Free Thyroxine (FT4), Free Triiodothyronine (FT3),
      Thyroid stimulating hormone (TSH), Thyroid peroxidase antibody (TPOAb) and
      thyroglobulin antibody (TgAb) were done. RESULTS: Significantly higher serum
      ferritin and iron and significantly lower total iron binding capacity were found
      in patients compared with controls (mean serum ferritin was 1665.2+/-1387.65ng/ml
      in patients versus 192.55+/-107.2 ng/ml in controls with p value of 0. 007, mean
      serum iron was 164+/-83.9 ug/dl in patients versus 89.5+/-4.5ug/dl in controls
      with p value of 0.039, mean TIBC was 238+/-44.5ug/dl in patients versus 308+/-11
      ug/dl in controls with p value of 0.001). 'Significantly higher serum TSH and
      significantly lower Free T3 and Free T4 were found in patients compared with
      controls with no significant correlation between thyroid hormones and serum
      ferritin' (mean serum TSH was 4.61+/-1.2 uIU/mL in patients versus 2.11 +/- 0.54
      uIU /mL in controls with p value of 0. 045, mean serum FT3 was 2.61 +/-1.3 pg/mL
      versus 3.93+/-0.47 pg/mL in controls with p value of 0.027, mean serum FT4 0.91+/
      0.174 ng/dL versus 1.44+/- 0.164 ng/dL in controls with p value of 0.047, r = -
      0. 008 and p value of 0. 973 for correlation between free T4 and serum ferritin,
      r = -0. 028 and p value of 0. 9 for correlation between TSH and serum ferritin
      and r= - 0.259 and p value of 0.27 for correlation between T3 and serum
      ferritin). There were no significant differences between patients and controls
      regarding thyroid peroxidase antibody and thyroglobulin antibody (mean serum
      thyroid peroxidase antibody was 22.45 +/- 4.32 in patients versus 22.45 +/- 3.21
      in controls with p value of 0.98, mean serum thyroglobulin antibody was 12.32 +/-
      2.65 in patients versus 12.99 +/- 2.34 in controls with p value of 0.76.
      CONCLUSION: Thyroid hormones deficiency may occur in some patients with SCD.
      RECOMMENDATIONS: 'Regular assessment of thyroid function in children with SCD may
      be recommended as they are more vulnerable to develop hypothyroidism and may
      require replacement therapy'.

PMID- 30207253
TI  - Anti-Trichomonas vaginalis activity of 1,10-phenanthroline-5,6-dione-based
      metallodrugs and synergistic effect with metronidazole.
AB  - Trichomonas vaginalis is responsible for the most common non-viral, sexually
      transmitted infection, human trichomoniasis, and is associated with an increased
      susceptibility to HIV. An escalation in resistance (2.5-10%) to the clinical
      drug, metronidazole (MTZ), has been detected and this compound also has adverse
      side-effects. Therefore, new treatment options are urgently required. Herein, we
      investigate the possible anti-T. vaginalis activity of 1,10-phenanthroline-5,6
      dione (phendione) and its metal complexes, [Ag(phendione)2]ClO4 and
      [Cu(phendione)3](ClO4)2.4H2O. Minimum inhibitory concentration (MIC) against T.
      vaginalis ATCC 30236 and three fresh clinical isolates and mammalian cells were
      performed using serial dilution generating IC50 and CC50 values. Drugs
      combinations with MTZ were evaluated by chequerboard assay. A strong anti-T.
      vaginalis activity was found for all test compounds. IC50 values obtained for
      [Cu(phendione)3](ClO4)2.4H2O were similar or lower than those obtained for MTZ.
      In vitro assays with normal cells showed low cytotoxicity and
      [Cu(phendione)3](ClO4)2.4H2O presented a high selectivity index (SI) for
      fibroblasts (SI = 11.39) and erythrocytes (SI > 57.47). Chequerboard assay
      demonstrated that the combination of [Cu(phendione)3](ClO4)2.4H2O with MTZ leads
      to synergistic interaction, which suggests distinct mechanisms of action of the
      copper-phendione complex and avoiding the MTZ resistance pathways. Our results
      highlight the importance of phendione-based drugs as potential molecules of
      pharmaceutical interest.

PMID- 30207252
TI  - Differential miRNA Expression Profiles in Cumulus and Mural Granulosa Cells from
      Human Pre-ovulatory Follicles.
AB  - BACKGROUND: Mural Granulosa Cells (MGCs) and Cumulus Cells (CCs) are two
      specialized cell types that differentiate from a common progenitor during
      folliculogenesis. Although these two cell types have specialized functions and
      gene expression profiles, little is known about their microRNA (miRNA) expression
      patterns. OBJECTIVE: To describe the miRNA profile of mural and cumulus granulosa
      cells from human preovulatory follicles. METHODS: Using small RNA sequencing, we
      defined the miRNA expression profiles of human primary MGCs and CCs, isolated
      from healthy women undergoing ovum pick-up for in vitro Fertilization (IVF).
      RESULTS: Small RNA sequencing revealed the expression of several hundreds of
      miRNAs in MGCs and CCs with 53 miRNAs being significantly differentially
      expressed between MGCs and CCs. We validated the differential expression of miR
      146a-5p, miR-149-5p, miR-509-3p and miR-182-5p by RT-qPCR. Analysis of proven
      targets revealed 37 targets for miR-146a-5p, 43 for miR-182-5p, 2 for miR-509-3p
      and 9 for miR-149-5p. Gene Ontology (GO) analysis for these 4 target gene sets
      revealed enrichment of 12 GO terms for miR-146a-5p and 10 for miR-182-5p. The GO
      term ubiquitin-like protein conjugation was enriched within both miRNA target
      gene sets. CONCLUSION: We generated miRNA expression profiles for MGCs and CCs
      and identified several differentially expressed miRNAs.

PMID- 30207254
TI  - Suicidal ideation and other persisting symptoms after CBT or antidepressant
      medication treatment for major depressive disorder.
AB  - BACKGROUND: Persisting symptoms after treatment for major depressive disorder
      (MDD) contribute to ongoing impairment and relapse risk. Whether cognitive
      behavior therapy (CBT) or antidepressant medications result in different profiles
      of residual symptoms after treatment is largely unknown. METHODS: Three hundred
      fifteen adults with MDD randomized to treatment with either CBT or antidepressant
      medication in the Predictors of Remission in Depression to Individual and
      Combined Treatments (PReDICT) study were analyzed for the frequency of residual
      symptoms using the Montgomery Asberg Depression Rating Scale (MADRS) item scores
      at the end of the 12-week treatment period. Separate comparisons were made for
      treatment responders and non-responders. RESULTS: Among treatment completers (n =
      250) who responded to CBT or antidepressant medication, there were no significant
      differences in the persistence of residual MADRS symptoms. However, non
      responders treated with medication were significantly less likely to endorse
      suicidal ideation (SI) at week 12 compared with those treated with CBT (non
      responders to medication: 0/54, 0%, non-responders to CBT: 8/30, 26.7%; p =
      .001). Among patients who terminated the trial early (n = 65), residual MADRS
      item scores did not significantly differ between the CBT- and medication-treated
      groups. CONCLUSIONS: Depressed adults who respond to CBT or antidepressant
      medication have similar residual symptom profiles. Antidepressant medications
      reduce SI, even among patients for whom the medication provides little overall
      benefit.

PMID- 30207255
TI  - The contribution of brain imaging to the understanding of psychopathy.
AB  - Psychopathy is a personality type characterized by both callous emotional
      dysfunction and deviant behavior that affects society in the form of actions that
      harm others. Historically, researchers have been concerned with seeking data and
      arguments to support a neurobiological foundation of psychopathy. In the past few
      years, increasing research has begun to reveal brain alterations putatively
      underlying the enigmatic psychopathic personality. In this review, we describe
      the brain anatomical and functional features that characterize psychopathy from a
      synthesis of available neuroimaging research and discuss how such brain anomalies
      may account for psychopathic behavior. The results are consistent in showing
      anatomical alterations involving primarily a ventral system connecting the
      anterior temporal lobe to anterior and ventral frontal areas, and a dorsal system
      connecting the medial frontal lobe to the posterior cingulate cortex/precuneus
      complex and, in turn, to medial structures of the temporal lobe. Functional
      imaging data indicate that relevant emotional flow breakdown may occur in both
      these brain systems and suggest specific mechanisms via which emotion is
      anomalously integrated into cognition in psychopathic individuals during moral
      challenge. Directions for future research are delineated emphasizing, for
      instance, the relevance of further establishing the contribution of early life
      stress to a learned blockage of emotional self-exposure, and the potential role
      of androgenic hormones in the development of cortical anomalies.

PMID- 30207256
TI  - Microbiota-gut-brain research: a critical analysis.
AB  - Microbiota-gut-brain (MGB) research is a fast-growing field of inquiry with
      important implications for how human brain function and behaviour are understood.
      Researchers manipulate gut microbes ('microbiota') to reveal connections between
      intestinal microbiota and normal brain functions (e.g., cognition, emotion,
      memory) or pathological states (e.g., anxiety and mood disorders, neural
      developmental disorders such as autism). Many claims are made about causal
      relationships between gut microbiota and human behaviour. By uncovering these
      relationships, MGB research aims to offer new explanations of mental health and
      potential avenues of treatment.So far, limited evaluation has been made of MGB's
      methods and its core experimental findings, many of which are extensively
      reiterated in copious reviews of the field. These factors, plus the self-help
      potential of MGB, have combined to encourage uncritical public uptake of MGB
      discoveries. Both social and professional media focus on the potential for
      dietary intervention in mental health, and causal relationships are assumed to be
      established.Our target article has two main aims. One is to examine critically
      the core practices and findings of experimental MGB research, and to raise
      questions about them for brain and behavioural scientists who may not be familiar
      with the field. The other is to challenge the way in which MGB findings are
      presented. Our positive goal is to suggest how current problems and weaknesses
      may be addressed, in order for both scientific and public audiences to gain a
      clearer picture of MGB research and its strengths and limitations.

PMID- 30207257
TI  - An acoustic study of lexical stress contrastivity in children with and without
      autism spectrum disorders.
AB  - In this exploratory study, we examined stress contrastivity within real word
      productions elicited via picture naming in 20 children with autism spectrum
      disorders (ASD) and 20 typical peers group-wise matched on age and vocabulary.
      Targets had a dominant pattern of lexical stress beginning with a strong-weak
      pattern (SW: 'caterpillar', 'butterfly') or a non-dominant pattern of lexical
      stress beginning with a weak-strong pattern (WS: 'tomato', 'potato'). Children
      produced each target twice (n = 320 productions). Acoustic measures were made for
      the duration, fundamental frequency, and intensity of the first two vowels for
      each word production. For vowel duration and fundamental frequency, children with
      ASD and typical peers produced a similar magnitude of stress contrastivity for SW
      and WS words. However, there was a significant group difference in the way
      contrastivity in intensity was realised for WS words whereby children with ASD
      produced less stress contrastivity than typical peers. Bayesian analyses were in
      line with our interpretation of our frequentist analyses.

PMID- 30207258
TI  - Linking genes, circuits, and behavior: network connectivity as a novel
      endophenotype of externalizing.
AB  - BACKGROUND: Externalizing disorders are known to be partly heritable, but the
      biological pathways linking genetic risk to the manifestation of these costly
      behaviors remain under investigation. This study sought to identify neural
      phenotypes associated with genomic vulnerability for externalizing disorders.
      METHODS: One-hundred fifty-five White, non-Hispanic veterans were genotyped using
      a genome-wide array and underwent resting-state functional magnetic resonance
      imaging. Genetic susceptibility was assessed using an independently developed
      polygenic score (PS) for externalizing, and functional neural networks were
      identified using graph theory based network analysis. Tasks of inhibitory control
      and psychiatric diagnosis (alcohol/substance use disorders) were used to measure
      externalizing phenotypes. RESULTS: A polygenic externalizing disorder score (PS)
      predicted connectivity in a brain circuit (10 nodes, nine links) centered on left
      amygdala that included several cortical [bilateral inferior frontal gyrus (IFG)
      pars triangularis, left rostral anterior cingulate cortex (rACC)] and subcortical
      (bilateral amygdala, hippocampus, and striatum) regions. Directional analyses
      revealed that bilateral amygdala influenced left prefrontal cortex (IFG) in
      participants scoring higher on the externalizing PS, whereas the opposite
      direction of influence was observed for those scoring lower on the PS. Polygenic
      variation was also associated with higher Participation Coefficient for bilateral
      amygdala and left rACC, suggesting that genes related to externalizing modulated
      the extent to which these nodes functioned as communication hubs. CONCLUSIONS:
      Findings suggest that externalizing polygenic risk is associated with disrupted
      connectivity in a neural network implicated in emotion regulation, impulse
      control, and reinforcement learning. Results provide evidence that this network
      represents a genetically associated neurobiological vulnerability for
      externalizing disorders.

PMID- 30207259
TI  - New onset of depression in aging women and men: contributions of social,
      psychological, behavioral, and somatic predictors in the community - CORRIGENDUM.

PMID- 30207260
TI  - Affective reactivity to daily racial discrimination as a prospective predictor of
      depressive symptoms in African American graduate and postgraduate students.
AB  - This study examined whether individual differences in affective reactivity,
      defined as changes in positive or negative affect in response to daily racial
      discrimination, predicted subsequent depressive symptoms. Participants were
      African American graduate and postgraduate students (N = 174; M age = 30 years)
      recruited for a measurement-burst study. Data on depressive symptoms were
      gathered at two assessment points 1 year apart. Affective reactivity data was
      obtained from participants via a 14-day diary study of daily racial
      discrimination and affect. Participants who experienced pronounced increases in
      negative affect on days when racial discrimination occurred had elevated
      depressive symptoms 1 year later. Heightened positive affect reactivity was also
      associated with more depressive symptoms at follow-up. The results suggest that
      affective reactivity (either greater increases in negative affect or greater
      decreases in positive affect in the context of racial discrimination) may be an
      underlying psychological mechanism that confers vulnerability to future
      depressive symptoms.

PMID- 30207261
TI  - Reforming care without bureaucracy.
AB  - The Care Programme Approach was a valiant attempt to improve the aftercare of
      people with severe mental illness after discharge from hospital. It was
      introduced as a response to a scandal, not an advance in knowledge, and has
      always suffered by being a reaction to events rather than a trailblazer for the
      future. It may have dragged the worst of care upwards, but at the expense of
      creating a bureaucratic monstrosity that has hindered good practice by excessive
      attention to risk, and vastly increased paperwork with intangible benefit. It
      needs to be simplified to allow practitioners greater scope for collaborative
      solutions, less minatory oversight and better use of strained
      resources.Declaration of interestNone.

PMID- 30207262
TI  - Trends in sweetened beverages consumption among adults in the Brazilian capitals,
      2007-2016.
AB  - OBJECTIVE: To analyse trends in sweetened beverages consumption among adults in
      Brazil between 2007 and 2016. DESIGN: A time-series analysis, with data from the
      Surveillance System of Risk and Protection Factors for Chronic Diseases by
      Telephone Survey (VIGITEL). The prevalence of regular consumption (>=5 d/week),
      the average daily consumption (millilitres) and the prevalence of non-consumption
      of these beverages were analysed. The temporal variations of the indicators were
      calculated by linear regression. The analyses were performed for the complete set
      of the evaluated population and stratified by sociodemographic characteristics.
      SETTING: Brazilian capitals and Federal District. SUBJECTS: Brazilian adults aged
      >=18 years (n 519 641). RESULTS: There was a reduction in both regular and
      average daily consumption of sugar- and artificially sweetened beverages (-1.28
      percentage points (pp)/year, P=0.001 and -9.63 ml/year, P=0.001, respectively).
      The same result regarding regular consumption was found when only sugar-sweetened
      beverages were analysed (-1.11 pp/year, P=0.011). Similar trends were identified
      in the stratified analyses, with a greater magnitude of reduction among males,
      young adults, those with higher schooling and residents of more developed
      regions. Coincidentally, there was an increase in the prevalence of adults who
      did not consume sweetened beverages (1.54 pp/year, P=0.005). CONCLUSIONS: The
      consumption of sweetened beverages decreased during the period. However, a
      significant portion of the population still referred a daily consumption of these
      beverages.

PMID- 30207263
TI  - Recommendations from the Association for European Paediatric and Congenital
      Cardiology for clinical training in paediatric heart failure and transplantation.
AB  - Advanced medical and surgical treatment of heart failure and management of
      patients following heart transplantation is an emerging area. Treatment options
      at various levels are becoming available in an increasing number of countries.
      This rapidly evolving field involves a complex multi-disciplinary approach with a
      number of complementary medical and surgical strategies, including
      pharmacotherapy, structural cardiac interventions, electrophysiological
      optimisation, mechanical circulatory support, and heart transplantation.
      Furthermore, the importance of psycho-social support and care of patients and
      their families cannot be overstated. The aforementioned challenges and dynamics
      of new developments require guidance for core and advanced medical training in
      heart failure and transplantation. The Association for European Paediatric and
      Congenital Cardiology working group "pulmonary hypertension, heart failure and
      transplantation" has produced this document as an expert consensus statement;
      however, all recommendations must be considered and applied in the context of the
      local and national infrastructure and legal regulations.

PMID- 30207264
TI  - Efficiency of different incubation systems for the in vitro production of bovine
      embryos.
AB  - SummaryThis study aimed to compare the efficiency of different incubation systems
      for in vitro embryo production in bovine. Oocytes/embryos were cultured in three
      incubators: conventional - CONV, mini bench - MINI and portable - PORT. After in
      vitro maturation (IVM), oocytes were verified for maturation rate. The remaining
      structures were submitted to in vitro fertilization and culture to verify
      cleavage (day 2) and blastocyst (day 7) rates. Reactive oxygen species (ROS) were
      evaluated in post-IVM oocytes and embryos (days 2 and 7) using arbitrary
      fluorescence units (AFUs). No significant difference (P>0.05) was observed for
      maturation rate. The CONV system (74.0%) produced the highest cleavage rate
      (P0.05) to MINI (65.0%). The same pattern and differences were observed for
      blastocyst rate: CONV (33.3%), MINI (32.3%) and PORT (21.9%). ROS levels were not
      different (P>0.05) in post-IVM oocytes: CONV (35.6+/-4.5), MINI (29.4+/-4.0) and
      PORT (35.6+/-4.5). For day-2 embryos, ROS levels were higher (P0.05) was observed
      in blastocysts. In conclusion, although it produced high ROS levels at day 2 of
      culture, the MINI system was as efficient as the CONV system for blastocyst
      production. This option may be an interesting and economical for the in vitro
      embryo industry.

PMID- 30207265
TI  - Prevalence of Posttraumatic Stress Disorder (PTSD) and Its Correlates Among
      Junior High School Students at 53 Months After Experiencing an Earthquake.
AB  - OBJECTIVE: To identify the prevalence of posttraumatic stress disorder (PTSD) and
      its determinants among adolescents more than 4 years after the 2008 Wenchuan
      earthquake. METHOD: Adolescents (1,125 total) from 2 junior high schools in areas
      affected by the catastrophic earthquake were followed up for 3 years. The self
      rating PTSD scale based on the Manual of Mental Disorders, 4th Edition (DSM-IV)
      and the Chinese Classification and Diagnostic Criteria of Mental Disorders, 2nd
      Edition, Revised (CCMD-2-R) was collected at 53 months, and determinant data were
      collected repeatedly. Logistic regression was used for a determinants analysis.
      RESULTS: The prevalence of overall PTSD was 23.4% among the sample. The risk
      factors for PTSD were older age (OR=1.52, 95% CI: 1.20~1.92), and death or injury
      of a family member in the earthquake (OR=1.61, 95% CI: 1.09~2.37). Adolescents
      who had moderate-to-severe common mental health problems were more likely to have
      PTSD symptoms, with ORs from 3.98 to 17.67 (All P<0.05). Self-esteem remained a
      protective factor for PTSD regardless of age, whereas positive coping was a
      protective factor for PTSD when adolescents were older. CONCLUSION: PTSD symptoms
      among adolescent survivors of a catastrophic earthquake seemed to persist over
      time. Long-term interventions are needed to alleviate PTSD symptoms among
      adolescent survivors. (Disaster Med Public Health Preparedness. 2018;page 1 of
      5).

PMID- 30207266
TI  - Anatomy of posterior cruciate ligament retained in a posterior cruciate ligament
      retaining total knee replacement: a cadaveric study.
AB  - BACKGROUND: Recent evidence has highlighted a risk that the majority of posterior
      cruciate ligament (PCL) is removed while making bone cuts in tibia and femur
      during total knee replacement surgery. Aim of this cadaveric study is to
      calculate how much PCL footprint is retained in a PCL retaining prosthesis after
      routine tibial and femoral cuts are made.  Methods: Twelve paired formalin-fixed
      Indian cadaveric knees were studied. Knees were disarticulated and all soft
      tissues were circumferentially removed from the tibia and femur. Footprints of
      antero-lateral and postero-medial bundles were marked on tibia and femur.
      Proximal tibial and distal femoral cuts were made using standard cutting jigs
      (Zimmer NexGen LPS). Digital photographs were taken with a magnification marker
      attached on the bone before and after making the cuts. Area of PCL insertion
      before and after the bone cuts was measured using software ImageJ (National
      Institute of Health). RESULTS: Footprint on tibial side was reduced by 9.1%, and
      on femoral side by 21.8%. Footprint of AL bundle was reduced by 24.3% on the
      tibial side and by 15.3% on the femoral side. Footprint of PM bundle on tibia was
      not affected by the bone cut but was reduced by 18.5% on the femoral side.
      CONCLUSION: Tibial and femoral insertions of PCL are relatively well preserved
      after bone cuts are made in a posterior cruciate retaining TKR. There is
      differential sectioning of antero-lateral and postero-medial bundles of PCL on
      tibial and femoral sides.

PMID- 30207267
TI  - The description of two new species of Chloromyxum from skates in the Argentine
      Sea reveals that a limited geographic host distribution causes phylogenetic
      lineage separation of myxozoans in Chondrichthyes.
AB  - During a survey on the myxosporean fauna of Rajiformes from the Atlantic coast of
      Argentina, in waters off Buenos Aires Province (34 degrees -42 degrees S; 53
      degrees -62 degrees W), the gall bladders of 217 specimens belonging to seven
      species of skates, representatives of two families, were examined. As a result,
      three species of Chloromyxum Mingazzini, 1890, namely C. atlantoraji n. sp., C.
      zearaji n. sp. and C. riorajum Azevedo, Casal, Garcia, Matos, Teles-Grilo and
      Matos, 2009 were found infecting three endemic host species, the spotback skate
      Atlantoraja castelnaui (Arhynchobatidae), the yellownose skate Zearaja chilensis
      (Rajidae) and the Rio skate Rioraja agassizii (Arhynchobatidae), respectively.
      These species were described based on myxospore morphology and morphometry
      characterization, as well as by providing their small subunit ribosomal DNA (SSU
      rDNA) sequences. The SSU rDNA-based phylogenetic analyses showed that these three
      species constituted a well-established monophyletic subclade within the marine
      Chloromyxum clade, while branches subtending the other Chloromyxum species were
      poorly resolved or unresolved, independently of the host taxonomic identities
      (Carchariniformes, Myliobatiformes, Orectolobiformes, Pristiophoriformes,
      Rajiformes, Squaliformes and Torpediniformes) and/or host geographic distribution
      (Atlantic coast of Portugal, Atlantic coast of the USA, Australian waters or
      Mediterranean Sea). The possible causes of these discrepancies are discussed,
      providing new insights into the phylogeny of the marine Chloromyxum clade.

PMID- 30207269
TI  - Body mass index, waist circumference, body fat mass, and risk of developing
      hypertension in normal-weight children and adolescents.
AB  - BACKGROUND AND AIMS: We prospectively examined the association between three
      adiposity indices, including body mass index (BMI), waist circumference (WC), and
      percentage of body fat (PBF), and risk of hypertension in normal-weight Chinese
      children. METHODS AND RESULTS: The current study included 1526 (713 boys and 813
      girls) normal-weight Chinese children (age 6-14 years old), who were free of
      hypertension at baseline (2014). Heights, body weight, WC, and PBF (estimated by
      bioelectrical impedance analysis) were measured at the baseline. Blood pressure
      was repeatedly measured in 2014, 2015 and 2016. Hypertension was defined as
      either high systolic blood pressure and/or high diastolic blood pressure,
      according to age- and sex-specific 95th percentile for Chinese children. We used
      Cox proportional hazards model to calculate the association between exposures and
      hypertension. We identified 88 incident hypertension cases during two years of
      follow up. High BMI was associated with high risk of developing hypertension
      after adjusting for potential confounders. The adjusted hazard ratio for
      hypertension was 2.88 (95% CI: 1.24, 6.69) comparing two extreme BMI quartiles.
      Each SD increase of BMI (~1.85 kg/m2) was associated with a 32% higher likelihood
      to developing hypertension (Hazard ratio = 1.32; 95% CI: 1.003, 1.73). In
      contrast, we did not find significant associations between WC or PBF and higher
      hypertension risk (p-trend >0.2 for both). CONCLUSION: High BMI, but not WC and
      PBF, was associated with high risk of hypertension in normal-weight Chinese
      children.

PMID- 30207268
TI  - Fermented dairy products, diet quality, and cardio-metabolic profile of a
      Mediterranean cohort at high cardiovascular risk.
AB  - BACKGROUND AND AIMS: Fermented dairy products have been associated with a better
      diet quality and cardio-metabolic profile. However, in Mediterranean populations,
      these associations have not been well characterized. The aim of this study was to
      assess the diet quality and the associations between the consumption of total
      fermented dairy products and their subtypes and the prevalence of Metabolic
      Syndrome (MetS) components in a Mediterranean population at high cardiovascular
      risk. METHODS AND RESULTS: Baseline cross-sectional analyses were conducted on
      6,572 men and women (mean age: 65 years) with overweight or obesity and MetS
      recruited into the PREDIMED-Plus cohort. A 143-item Food Frequency Questionnaire
      (FFQ) was used, and anthropometrical, biochemical, and blood pressure
      measurements were recorded. Multivariate-adjusted Cox regressions were fitted to
      analyze the association between quartiles of consumption of fermented dairy
      products and their subtypes and MetS components to estimate the relative risk
      (RR) and 95% confidence intervals (95% CIs). Participants who were high consumers
      of fermented dairy products reported a higher consumption of fruit, vegetables,
      fish, nuts, and whole bread and a lower consumption of white bread, alcohol, and
      cookies. Participants in the higher quartile showed a lower prevalence of the low
      HDL-cholesterol component of the MetS (RR=0.88; 95% CI: 0.78-0.98) than those in
      the lowest quartile of cheese consumption. Cheese consumption was inversely
      associated with the prevalence of hypertriglyceridemia. Total fermented dairy
      products, yogurt, and its types were not associated with any of the MetS
      components. CONCLUSIONS: Compared to nonconsumers, participants consuming
      fermented dairy products reported a better diet quality and, particularly, cheese
      consumers presented a lower prevalence of hypertriglyceridemia and low HDL
      cholesterol plasma levels, which are MetS components.

PMID- 30207270
TI  - Fruit, vegetable consumption and blood pressure in healthy adolescents: A
      longitudinal analysis from the LabMed study.
AB  - BACKGROUND AND AIMS: The associations between fruit and vegetable consumption and
      high blood pressure among adults are well studied. Nonetheless, data on the
      influence of a low consumption of fruit and vegetables on cardiovascular disease
      risk, particularly blood pressure, among healthy adolescents are scarce.
      Therefore, we aim to analyse the associations between fruit and/or vegetable
      intake and blood pressure over a two-year period in healthy adolescents. METHODS
      AND RESULTS: As part of a cohort, 606 adolescents from the LabMed Physical
      Activity study were evaluated in 2011 (baseline) and 2013 (follow-up). Blood
      pressure was measured according to standardized procedures and fruit and
      vegetable consumption was assessed with a food frequency questionnaire.
      Anthropometric variables, socioeconomic status, pubertal stage and lifestyle
      determinants were gathered and used as confounders. Prospective associations
      between fruit and/or vegetable intake and blood pressure were examined using
      generalized linear models. Girls who consumed more fruit at baseline had a
      significant decrease in diastolic blood pressure at follow-up [unstandardized
      beta: -0.005 mmHg (95%CI: -0.01; -0.0002) (p = 0.038)]. CONCLUSION: In apparently
      healthy adolescents, fruit intake may already start to have an effect in blood
      pressure. Girls who consumed more fruit exhibited lower levels of diastolic blood
      pressure.

PMID- 30207272
TI  - Molecular evidence and diversity of the spotted-fever group Rickettsia spp. in
      small mammals from natural, suburban and urban areas of Eastern Slovakia.
AB  - Rickettsiae of the spotted fever group are considered as emerging pathogens;
      ticks, fleas and mites are known to be their vectors. However, the prevalence and
      species diversity of rickettsiae in small mammals and the role of these hosts in
      the circulation of bacteria are much less studied. During 2014-2016, a total of
      250 small mammals (Apodemus agrarius, Apodemus flavicollis, Apodemus uralensis,
      Myodes glareolus, Crocidura leucodon, Crocidura suaveolens, Micromys minutus,
      Microtus arvalis, Microtus subterraneus, Neomys fodiens and Sorex minutus) were
      captured in natural, suburban and urban habitats of eastern Slovakia. Ear
      biopsies of 245 individuals were examined for the presence of SFG rickettsiae by
      molecular methods. The overall prevalence of Rickettsia spp. in small mammals was
      11%. The predominant species, Rickettsia helvetica was confirmed in the striped
      field mouse (A. agrarius), the yellow-necked mouse (A. flavicollis), the bank
      vole (M. glareolus) and the common vole (M. arvalis) in natural and suburban
      habitats, followed by Rickettsia sp. closely related to R. felis identified in A.
      flavicollis captured in a suburban habitat. Finally, R. slovaca was found in only
      one yellow-necked mouse (A. flavicollis) captured in a natural habitat, with the
      sympatric occurrence of Dermacentor marginatus and Dermacentor reticulatus ticks.
      We assume the presence of R. slovaca especially in sites with the occurrence of
      Dermacentor spp. All small mammals captured in the urban habitat tested were
      negative for the presence of rickettsiae. This study brings the first molecular
      evidence of R. slovaca in a rodent captured in Slovakia. Rickettsia sp. closely
      related to R. felis was first time detected in A. flavicollis in suburban site of
      Slovakia. The highest species diversity of rickettsiae was observed in A.
      flavicollis, and the highest prevalence of bacteria was recorded in M. glareolus.
      The highest occurrence of rickettsiae-positive small mammals was recorded during
      the spring and autumn months, May, June and September, respectively. This may be
      related with the seasonal activity of the tick vectors. This study confirms the
      long-term persistence of Rickettsia spp. in small mammals in natural and suburban
      habitats of Slovakia. Some rodent species that have a wider ecological valency
      may contribute to the maintenance, circulation and dissemination of rickettsiae
      within and out the natural foci more significantly than those species that have
      narrower relation to the certain type of habitat.

PMID- 30207273
TI  - Development of a recombinant TaSP-based Dot-ELISA for detection of Theileria
      annulata infection in cattle.
AB  - The study was conducted to develop and validate Dot-ELISA for the diagnosis of
      Theileria annulata infection in cattle using recombinant Theileria annulata
      surface protein (r-TaSP). The r-TaSP based indirect plate-ELISA was used as a
      reference test to compare the efficacy of the Dot-ELISA. The Dot-ELISA was
      optimized with 500 ng of antigen per dot, 1:150 dilution of serum and 1:1000
      dilution of secondary antibody for positive and negative reaction. A total of 17
      confirmed positive, 25 negative and 129 field sera samples were used to calculate
      the diagnostic accuracy of Dot-ELISA in comparison with indirect plate-ELISA. The
      diagnostic sensitivity and specificity of the Dot-ELISA was 95.8 per cent (95%
      CI, 93.1-97.2) and 80 per cent (95% CI, 48.1-96.2), respectively. The positive
      predictive value (PPV) of Dot-ELISA was 98.2 percent (95% CI, 95.5-99.7) and
      negative predictive value (NPV) was 61.6 percent (95% CI, 37-74). The positive
      and negative likelihood ratios were 4.79 (95% CI, 1.8-25.69) and 0.053 (95% CI
      0.03-1.4), respectively. The Dot-ELISA showed moderate agreement (k value, 0.67,
      95% CI, 0.36- 0.82) with indirect plate-ELISA. The developed Dot-ELISA is less
      expensive and convenient for the diagnosis of T. annulata infection in cattle
      under field conditions.

PMID- 30207271
TI  - Adipose tissue palmitoleic acid is inversely associated with nonfatal acute
      myocardial infarction in Costa Rican adults.
AB  - BACKGROUND AND AIMS: Animal models have shown that adipose-derived palmitoleic
      acid may act as a lipokine by conferring resistance to diet-induced obesity;
      however, human epidemiologic studies investigating this relationship thus far
      have not provided data in support of this hypothesis. Because metabolic syndrome
      and cardiovascular disease are intricately linked with the former being a major
      risk factor for the latter, we hypothesized that adipose-derived palmitoleic acid
      may be inversely associated with myocardial infarction. We examined whether
      adipose tissue palmitoleic acid was associated with nonfatal acute myocardial
      infarction in a representative population of Costa Rican adults. METHODS AND
      RESULTS: Odds ratios of nonfatal acute myocardial infarction by quintiles of
      adipose tissue palmitoleic acid were calculated using conditional logistic
      regression in a case-control study of 1828 cases and 1828 controls matched by
      age, sex, and area of residence. We observed an inverse relationship between
      nonfatal acute myocardial infarction and adipose tissue palmitoleic acid (OR for
      highest quintile compared to lowest quintile of palmitoleic acid: 0.55; 95% CI:
      0.41, 0.75; P for trend: <0.0001). We additionally observed a significant
      positive association between adipose tissue palmitoleic acid and high-density
      lipoprotein cholesterol. CONCLUSION: These data demonstrate an inverse
      association between adipose tissue palmitoleic acid and nonfatal acute myocardial
      infarction; however, further research is required in order to better understand
      the opposing associations between palmitoleic acid and high-density lipoprotein
      cholesterol and systolic blood pressure.

PMID- 30207274
TI  - Assessing the cellular and humoral immune response in Rhipicephalus sanguineus
      sensu lato (Acari: Ixodidae) infected with Leishmania infantum (Nicolle, 1908).
AB  - The aim of this study was to evaluate aspects of the innate cellular and humoral
      immune response by evaluating hemocyte dynamics, phagocytosis, phenoloxidase (PO)
      activity and nitric oxide (NO) production in Rhipicephalus sanguineus sensu lato
      (s.l.) (Acari: Ixodidae) infected with Leishmania infantum and to assess the
      persistence of parasites at time 0 and 1, 2, 5, and 7 days post-infection (dpi).
      The total and differential count of the five types of hemocytes circulating in
      the hemolymph of R. sanguineus s.l. females showed the average total number of
      hemocytes in the group infected with L. infantum to be significantly higher (p <
      0.05) on the 1st and 2nd dpi compared to the control group. The hemocyte
      differential count showed that the average number of plasmatocytes and
      granulocytes increased significantly on the 1st, 2nd, and 5th dpi with L.
      infantum compared to the control group (p < 0.001). Phagocytosis assays revealed
      that plasmatocytes and granulocytes were able to perform phagocytosis of latex
      beads and L. infantum on the 1st and 2nd dpi, respectively. NO production was
      significantly increased (p < 0.001) on the 1st, 2nd, and 5th dpi with L. infantum
      and PO activity increased significantly (p < 0.05) only on the 5th dpi. L.
      infantum DNA was significantly increased (p < 0.001) on the 5th and 7th dpi
      compared to time 0. Although there are no studies describing the response of R.
      sanguineus s.l. to an infection with L. infantum, these results suggest that R.
      sanguineus s.l. activates the cellular and humoral immune response after
      infection with L. infantum. Further studies are however, needed to assess the
      impact of such a response on fighting infection.

PMID- 30207275
TI  - Molecular detection and characterization of tick-borne protozoan and rickettsial
      pathogens isolated from cattle on Pemba Island, Tanzania.
AB  - Tick-borne diseases cause significant losses to livestock production in tropical
      and subtropical regions. In Tanzania, detailed studies on tick-borne pathogens in
      cattle using sensitive molecular detection methods are scarce. In this study, we
      investigated the occurrence of Theileria spp., Babesia spp., Anaplasma spp. and
      Ehrlichia spp. in 245 blood samples collected from cattle on Pemba Island,
      Tanzania. We used polymerase chain reaction (PCR) and gene sequencing to detect
      and identify pathogens. PCR screening revealed overall infection rates of 62.4%
      for Theileria spp., 17.6% for Babesia bigemina, 15.9% for Anaplasma marginale,
      7.4% for Ehrlichia ruminantium and 4.5% for Babesia bovis. Further analysis using
      sequences of Theileria spp. 18S rRNA revealed infection of cattle with Theileria
      mutans (68.6%), Theileria taurotragi (48.4%), Theileria parva (41.2%), and
      Theileria ovis (1.9%). Co-infections of cattle, with up to six tick-borne
      pathogens, were revealed in 46.9% of the samples. Sequence analysis indicated
      that T. parva p104, E. ruminantium pCS20 and A. marginale MSP-5 genes are
      conserved among cattle blood samples in Pemba, with 99.3%-100%, 99.6%-100% and
      100% sequence identity values, respectively. In contrast, the B. bigemina RAP-1a
      and B. bovis SBP-2 gene sequences were relatively diverse with 99.5%-99.9% and
      66.4%-98.7% sequence identity values respectively. The phylogenetic analyses
      revealed that T. parva p104, E. ruminantium pCS20 and A. marginale MSP-5 gene
      sequences clustered in the same clade with other isolates from other countries.
      In contrast, the B. bigemina RAP-1 and B. bovis SBP-2 gene sequences showed
      significant differences in the genotypes, as they appeared in separate clades.
      This study provides important data for understanding the epidemiology of tick
      borne diseases, and is expected to improve the approach for diagnosis and control
      of tick-borne diseases in Tanzania.

PMID- 30207276
TI  - Common occurrence of Theileria annulata and the first report of T. ovis in dairy
      cattle from Southern Xinjiang, China.
AB  - Bovine theileriosis is a common tick-born disease infected by Theileria spp.
      causing loss of beef and dairy cattle worldwide, therefore, the aim of this study
      was to determine the prevalence and genetic diversity of Theileria spp. in
      Southern Xinjiang Uyghur Autonomous Region, China. We screened 493 dairy cattle
      blood samples from Southern Xinjiang to detect Theileria spp. by PCR. The overall
      prevalence of Theileria spp. was 23.5% (116/493). The most frequent Theileria sp.
      was Theileria annulata 22.5% (111/493), followed by T. orientalis (0.6%, 3/493)
      and T. ovis (0.2%, 1/493). Additionally, one sample was co-infected with T.
      annulata and T. orientalis. Phylogenetic analysis showed that the 11 T. annulata
      Tams1 sequences grouped into three sequence clusters that belonged to group 2
      (Asia group) and shared 96.4% to 99.9% identity with to each other. Furthermore,
      our results revealed the presence of several T. orientalis MPSP genotypes (types
      1, 2, and 5) in this region. In this study, T. annulata was found to be the most
      prevalent Theileria species in dairy cattle from Southern Xinjiang. Theileria
      ovis was detected in one DNA sample of a free-grazing dairy cow from China for
      the first time.

PMID- 30207277
TI  - Biogeography of parasite abundance: latitudinal gradient and distance decay of
      similarity in the abundance of fleas and mites, parasitic on small mammals in the
      Palearctic, at three spatial scales.
AB  - We tested whether biogeographic patterns characteristic for biological
      communities can also apply to populations and investigated geographic patterns of
      variation in abundance of ectoparasites (fleas and mites) collected from bodies
      of their small mammalian hosts (rodents and shrews) in the Palearctic at
      continental, regional and local scales. We asked whether (i) there is a
      relationship between latitude and abundance and (ii) similarity in abundance
      follows a distance decay pattern or it is better explained by variation in
      extrinsic biotic and abiotic factors. We analysed the effect of latitude on mean
      intraspecific abundance using general linear models including proportional
      abundance of its principal host as an additional predictor variable. Then, we
      examined the relative effect of geographic distance, biotic and abiotic
      dissimilarities among regions, subregions or localities on the intraspecific
      dissimilarity in abundance among regions, subregions or localities using
      Generalized Dissimilarity Modelling. We found no relationship between latitude
      and intraspecific flea or mite abundance. In both taxa, environmental
      dissimilarity explained the largest part of the deviance of spatial variation in
      abundance, whereas the effect of the dissimilarity in the principal host
      abundance was of secondary importance and the effect of geographic distance was
      minor. These patterns were generally consistent across the three spatial scales,
      although environmental variation and dissimilarity in principal host abundance
      were equally important at the local scale in fleas but not in mites. We conclude
      that biogeographic patterns related to latitude and geographic distance do not
      apply to spatial variation of ectoparasite abundance. Instead, the geographic
      distribution of abundance in arthropod ectoparasites depends on their responses,
      mainly to the off-host environment and to a lesser extent the abundance of their
      principal hosts.

PMID- 30207278
TI  - Photoacoustic Oxygenation Quantification in Patients with Raynaud's: First-in
      Human Results.
AB  - The purpose of this study was to investigate the use of photoacoustic imaging for
      quantifying fingertip oxygenation as an approach to diagnosing and monitoring
      Raynaud's phenomenon. After 30 min of acclimation to room temperature, 22
      patients (7 patients with secondary Raynaud's associated to Scleroderma and 15
      healthy controls) provided informed consent to undergo fingertip Doppler imaging
      and high-frequency photoacoustic imaging before and 5, 15 and 30 min after cold
      stimulus (submerged hand in a 15  degrees C water bath for 1 min). High-frequency
      ultrasound and photoacoustic imaging was performed on the nail bed of each
      patient's second through fifth finger on their dominant hand, using a Vevo 2100
      LAZR system with an LZ-250 probe (Fujifilm VisualSonics, Toronto, ON, Canada) in
      oxy-hemoglobin quantification mode. During each exam, volumetric data across a 3
      mm span of data was acquired to produce a volumetric image of percent oxygenation
      and hemoglobin concentration. Changes in fingertip oxygenation between Raynaud's
      patients and healthy volunteers were compared, using receiver operator
      characteristic (ROC) analysis. Photoacoustic signal was detected in both the nail
      bed and nailfold in all study participants. Doppler ultrasound resulted in poor
      differentiation of Raynaud's patients from healthy volunteers, with an area under
      the ROC curve (Az) of 0.51. Photoacoustic imaging demonstrated improved accuracy
      at baseline (Az = 0.72), which improved when quantifying normalized changes after
      cold stimulus (Az = 0.89 5-min post stimulus, Az = 0.91 15-min post stimulus, and
      Az = 0.85 after stimulus). Oxygenation levels derived using photoacoustic imaging
      are able to identify patients with Raynaud's and safely evaluate their response
      to a cold stimulus over time.

PMID- 30207280
TI  - A pilot study to assess the safety and radiological performance of a new low
      profile locking plate for high tibial osteotomy.
AB  - BACKGROUND: We report the first results of a new low-profile titanium locking
      plate for fixation of opening wedge high tibial osteotomy (OWHTO). Short spacer
      plates have been associated with a high hardware complication rate, whilst fixed
      angle locking plates have been associated with a high incidence of soft tissue
      irritation. This plate aims to achieve stable fixation whilst maintaining a low
      profile, allowing space for combined procedures. METHODS: All patients undergoing
      OWHTO with the Activmotion plate were retrospectively reviewed. Patients were
      allowed to progress to full weight bearing after two weeks. Radiographic
      assessment included the medial proximal tibial angle (MPTA) and posterior tibial
      slope at six weeks and then three monthly until union. All complications were
      recorded. RESULTS: Thirty-seven patients with 40 OWHTOs were included in the
      study. The mean MPTA increased from 85.2 preoperatively to 91.9 postop. Tibial
      slope changed from 5.2 to 4.2 degrees . The correction was sustained until union
      with no loss of correction in the MPTA (median change 0.0, 95% CI for median (
      0.25, 0.4)) or tibial slope (mean increase 0.32, 95% CI (-0.02, 0.67)).
      CONCLUSIONS: In this pilot study the Activmotion plate raised no safety concerns
      with regard to implant related adverse events or loss of initial correction.
      Early rehabilitation with immediate partial weight bearing was possible and all
      cases proceeded to osteotomy union with the exception of one case that needed to
      undergo bone grafting with implant retention. Premature removal of the implant
      was necessary in four cases due to symptomatic hardware irritation.

PMID- 30207279
TI  - Popliteal vessel trauma: Surgical approaches and the vessel-first strategy.
AB  - BACKGROUND: In this study, we analyzed long-term outcomes following treatment of
      traumatic popliteal vascular injuries in an urban level I trauma center, using a
      vessel-first approach in the case of combined vascular and bony/ligamentous
      injuries and discussing the relative merits of the medial and posterior approach
      to popliteal vessels. METHODS: Data including patient demographics, mechanism and
      type of injury, severity of limb ischemia, Injury Severity Score (ISS), limb
      ischemia time, time to revascularization from admission, treatment strategy, type
      of vascular reconstruction, limb salvage and mortality were retrospectively
      collected in patients treated for traumatic popliteal vessel lesions. All
      patients in this study were operatively treated using medial and posterior
      approaches. A vessel-first approach was used where possible. RESULTS: Twenty-four
      patients (13 male) with a median age of 45 years (range 21-88) and popliteal
      vessel injury after traumatic knee dislocation (n = 10, 42%), proximal tibia
      fracture (n = 5, 21%), distal femur fracture (n = 4, 17%), blunt popliteal injury
      (n = 3, 12%) and penetrating trauma (n = 2, 8%) were identified. Twelve (50%)
      patients were treated via a medial approach and 12 (50%) via a posterior
      approach. All had injury of the popliteal artery (15 complete transection, eight
      local intimal disruption and one pseudoaneurysm) with seven having additional
      popliteal vein and five with nerve injury. Nineteen patients (88%) presented with
      limb ischemia Rutherford category >=II. Vessel reconstruction (four direct
      sutures, four patch plasties, 16 venous interposition/bypasses) was performed
      prior to bone/joint stabilization in 22 patients (92%). Thirty-day mortality was
      zero. Two above-knee amputations were performed within 30 days due to severe
      infection. During a median follow-up of 59 (range 12-143) months, there were no
      deaths and no amputations. At the end of follow-up, all patients denied
      claudication. CONCLUSIONS: The vessel-first strategy promises an excellent
      outcome, independent of the surgical approach needed to repair traumatic
      popliteal vessel injuries.

PMID- 30207281
TI  - A pilot study evaluating chemotherapy tolerability for breast cancer patients who
      have received prior treatment and chest radiation for Hodgkin Lymphoma.
AB  - MICROABSTRACT: Women treated with chest radiation for Hodgkin lymphoma (HL) have
      significantly higher risk of developing breast cancer, and little is known about
      how these patients tolerate chemotherapy for breast cancer. This small
      retrospective study identified 15 patients, noting that these patients tolerate
      proposed chemotherapy regimens for breast cancer in rates similar to those
      without prior HL and therapeutic radiation. PURPOSE: Women treated for Hodgkin
      lymphoma (HL) with chest radiation have significantly higher risk of developing
      breast cancer, and little is known about how these patients tolerate chemotherapy
      for breast cancer. METHODS: Women with breast cancer diagnosed from 1986-2015
      after radiation for HL were identified from hospitals and clinics in St. Paul and
      Minneapolis, Minnesota. Patient, tumor and treatment characteristics, and
      clinical outcomes were abstracted from medical records and summarized using
      descriptive statistics. Chemotherapy was defined as tolerated if all scheduled
      doses and cycles were completed without deviation from the initial plan, with
      lack of grade 3 or higher toxicity attributable to chemotherapy in categories
      including blood, cardiac, gastrointestinal, fatigue and pain. RESULTS: Forty-two
      patients with breast cancer and prior radiation for HL were identified, 15 of
      which received chemotherapy for breast cancer. We noted 75% tolerability of
      taxane-based and 100% tolerability of anthracycline-based chemotherapy,
      suggesting that most patients with prior radiation for HL tolerate chemotherapy
      for breast cancer. A subset of patients (N = 7) in this study were also treated
      with chemotherapy for HL prior to breast cancer diagnosis, and 86% (6 of 7) also
      tolerated chemotherapy for breast cancer. CONCLUSIONS: Treatment of breast cancer
      is strongly influenced by prior treatment of HL. Although this study was small
      and did not meet statistical significance, the data suggest that these patients
      tolerate proposed chemotherapy regimens for breast cancer in rates similar to
      those without prior HL and therapeutic radiation. Larger studies comparing
      specific chemotherapy dosing schedules are needed to address this complicated
      population.

PMID- 30207282
TI  - Benefit of crizotinib in a lung cancer patient with discordant ALK testing
      results.
AB  - Crizotinib is a first line treatment for patients with non-small cell lung cancer
      (NSCLC) harboring translocations in anaplastic lymphoma kinase (ALK). The current
      gold standard for determining ALK status is fluorescence in-situ hybridisation
      (FISH), but immunohistochemistry (IHC) is becoming increasingly popular due to
      lower cost. There are currently few reports on clinical outcomes with crizotinib
      therapy in patients who have tested negative by FISH and positive by IHC. A 53
      year old lifelong non-smoking, physically active male with newly diagnosed Stage
      IV NSCLC presented with shortness of breath on exertion one month prior to
      referral. Staging CT scan failed to show a discreet lung lesion, but the left
      lower lobe was collapsed due to pleural effusion. Pleural fluid showed
      adenocarcinoma and IHC was positive for an ALK mutation, while FISH was negative.
      Pre-treatment PET-CT showed hypermetabolic, enlarged lymph nodes in the
      mediastinum and retroperitoneum. Partially due to patient concerns about
      cytotoxic chemotherapy toxicity, crizotinib therapy was instituted. Repeat CT
      conducted two months after crizotinib initiation showed a decrease in
      lymphadenopathy at all sites compared to the PET-CT. Furthermore, the patient
      showed clinical improvement, with less drainage through his PleurX catheter and
      stability of his excellent performance status. After 12 months on crizotinib CT
      showed ongoing improvement in lymphadenopathy. His bloodwork has been stable, and
      he denies significant drug toxicity. This case illustrates a sustained response
      to crizotinib therapy in a patient with an ALK translocation identified by IHC,
      but with negative FISH testing. The literature suggests that the population with
      these discordant results could be up to 19% of ALK positive NSCLC. Patients in
      this subgroup who are receiving crizotinib should be identified and outcome data
      pooled. However, in the interim, oncologists may wish to consider targeted
      therapy for these discordant patients.

PMID- 30207283
TI  - Radiologic and autopsy findings in a case of fatal immune checkpoint inhibitor
      associated pneumonitis.
AB  - Oncologists are increasingly managing drug-induced pneumonitis in lung cancer
      patients treated with PD-1/PD-L1 immune checkpoint inhibitors. To date only few
      studies on the topic have described both radiologic and pathologic findings in
      these patients. Here, we report a fatal case of immune checkpoint inhibitor
      associated pneumonitis initially presenting with an organizing pneumonia, but who
      rapidly developed acute respiratory distress syndrome (confirmed histologically
      at the time of autopsy). As such, this case illustrates the need for clinicians
      to maintain a high index of suspicion for immune checkpoint inhibitor associated
      pneumonitis and have a low threshold to perform CT imaging in any symptomatic
      patient receiving checkpoint inhibition therapy. CLINICAL PRACTICE POINTS.

PMID- 30207284
TI  - Genomic profiling in advanced stage non-small-cell lung cancer patients with
      platinum-based chemotherapy identifies germline variants with prognostic value in
      SMYD2.
AB  - OBJECTIVE: The aim of the study was to investigate the relationship between
      germline variations as a prognosis biomarker in patients with advanced Non-Small
      Cell-Lung-Cancer (NSCLC) subjected to first-line platinum-based treatment.
      MATERIALS AND METHODS: We carried out a two-stage genome-wide-association study
      in non-small-cell lung cancer patients with platinum-based chemotherapy in an
      exploratory sample of 181 NSCLC patients from Caucasian origin, followed by a
      validation on 356 NSCLC patients from the same ancestry (Valencia, Spain).
      RESULTS: We identified germline variants in SMYD2 as a prognostic factor for
      survival in patients with advanced NSCLC receiving chemotherapy. SMYD2 alleles
      are associated to a decreased overall survival and with a reduced Time to
      Progression. In addition, enrichment pathway analysis identified 361 variants in
      40 genes to be involved in poorer outcome in advanced-stage NSCLC patients.
      CONCLUSION: Germline SMYD2 alleles are associated with bad clinical outcome of
      first-line platinum-based treatment in advanced NSCLC patients. This result
      supports the role of SMYD2 in the carcinogenic process, and might be used as
      prognostic signature directing patient stratification and the choice of therapy.
      MICROABSTRACT: A two-Stage Genome wide association study in Caucasian population
      reveals germline genetic variation in SMYD2 associated to progression disease in
      first-line platinum-based treatment in advanced NSCLC patients. SMYD2 profiling
      might have prognostic / predictive value directing choice of therapy and
      enlighten current knowledge on pathways involved in human carcinogenesis as well
      in resistance to chemotherapy.

PMID- 30207285
TI  - A novel algorithm to improve specificity in ovarian cancer detection.
AB  - BACKGROUND: Measurement of autoantibodies (AAbs) to tumor associated antigens has
      been proposed to aid in the early detection of ovarian cancer with high
      specificity. Here we describe a multiplex approach to evaluate selected peptide
      epitopes of p53 protein, and propose a novel approach to increase specificity and
      potentially sensitivity for discrimination between healthy women and women with
      cancerous masses. MATERIALS AND METHODS: 20-mer overlapping peptide epitopes of
      p53, generated by mapping the complete p53 sequence, were evaluated in a
      multiplex immunoassay for their detection of serum AAbs in patients with ovarian
      cancer, using Luminex technology. AAbs to the selected peptides and to p53 full
      length protein were then detected in a multiplex immunoassay evaluating 359 sera
      from healthy women and 285 sera from patients with early and late stage ovarian
      cancer. CA-125 levels were measured in all p53 AAb-positive sera. RESULTS: We
      considered the AAb results together to identify sera where both the full length
      protein and at least one selected peptide epitope were positive and chose cutoffs
      that reduced false positives from these AAbs to 1/359 samples, improving
      specificity. Using this combined approach, we could identify 7 AAb-positive
      patients that were negative for CA-125 (concentrations below 35 IU/mL); this
      represents 26% of the p53 positive patients in the total population. CONCLUSION:
      By detecting p53 AAbs in CA-125-negative sera, we demonstrated that combining
      measurement of AAbs to the full length p53 protein and one or more selected
      epitopes can potentially improve sensitivity and specificity for ovarian cancer
      detection.

PMID- 30207286
TI  - Prognostic value of total lesion glycolysis and metabolic active tumor volume in
      non-small cell lung cancer.
AB  - INTRODUCTION: To predict the outcome of patients with non-small cell lung cancer
      (NSCLC) the currently used prognostic system (TNM) is not accurate enough. The
      prognostic significance of the SUVmax measured by PET remains controversial. This
      study aims to evaluate the prognostic value in overall survival and progression
      free survival of SUVmax, the total lesion glycolysis (TLG) and the mean metabolic
      active volume (MATV) in NSCLC. METHODS: We retrospectively reviewed 105 patients
      (72 males, 33 females) with a new diagnosis of NSCLC (TNM stage I: 27.6%, II:
      10.5%, III: 40.9% and IV: 21.0%) who underwent scanning with a PET/CT. For VOI
      definition a semi-automatic delineation tool was used. On PET images SUVmax,
      SUVmean and MATV of the primary tumor and the whole tumor burden were measured.
      TLG and MATV were measured by using a threshold of 50% of SUVmax. RESULTS: OS and
      PFS are found to be higher in patients with low-SUVTmax and low-TLGT values. OS
      and PFS were significantly higher for low-SUVWTBmax, low-MATVWTB and low-TLGWTB
      values of the whole-tumor burden. Multivariate analysis of the whole-tumor burden
      revealed that the most important prognostic factors for OS are high MATVWTB and
      TLGWTB values, increasing stage and male gender. TLGWTB and stage are also
      independent prognosticators in PFS. CONCLUSION: Only whole-body TLG is of
      prognostic value in NSCLC for both OS and PFS. Stratification of patients by
      TLGWTB might complement outcome prediction but the TNM stage remains the most
      important determinant of prognosis. MICROABSTRACT: In order to predict the
      outcome of patients with non-small cell lung cancer (NSCLC) the currently used
      prognostic system (TNM) is not accurate enough. The prognostic significance of
      the standard uptake value (SUV) measured by PET remains controversial. This study
      aims to evaluate the prognostic value in overall survival (OS) and progression
      free survival (PFS) of the standard uptake value (SUV), the total lesion
      glycolysis (TLG) and the mean metabolic active volume (MATV) in NSCLC. The study
      reveals that TLG of the whole-tumor burden is an independent prognostic factor
      for OS and PFS in patients with NSCLC.

PMID- 30207287
TI  - CGH array for the identification of a compound heterozygous mutation in the
      CYP1B1 gene in a patient with bilateral anterior segment dysgenesis.

PMID- 30207288
TI  - Early disease relapse in a patient with colorectal cancer who harbors genetic
      variants of DPYD, TYMS, MTHFR and DHFR after treatment with 5-fluorouracil-based
      chemotherapy.
AB  - Background Early relapse in colorectal cancer (CRC) after curative resection is
      mainly attributed to the key determinants such as tumor histology, stage,
      lymphovascular invasion, and the response to chemotherapy. Case presentation
      Interindividual variability in the efficacy of adjuvant chemotherapy between
      patients receiving the same treatment may be ascribed to the patients' genetic
      profile. In this report, we highlight a clinical case of a patient with stage II
      CRC who relapsed within a short period after starting adjuvant chemotherapy and
      was later found to have multiple genetic polymorphisms in the DPYD, TYMS, MTHFR,
      and DHFR genes. Conclusions Based on the clinical data of the patient and the key
      role of these genes in 5-fluorouracil pathway, we hypothesize that these variants
      may contribute to the drug response and early relapse in CRC.

PMID- 30207289
TI  - Mirror therapy for phantom limb and stump pain: a randomized controlled clinical
      trial in landmine amputees in Cambodia.
AB  - Background and aims The aim of the study was to examine the effect of mirror and
      tactile therapy on phantom and stump pain in patients with traumatic amputations,
      with particular reference to amputees in low-income communities. Methods The
      study was conducted with an open, randomized, semi-crossover case-control design
      in rural Cambodia. A study sample of 45 landmine victims with trans-tibial
      amputations was allocated to three treatment arms; mirror therapy, tactile
      therapy, and combined mirror-and-tactile therapy. Non-responders from the mono
      therapy interventions were crossed over to the alternative intervention. The
      intervention consisted of 5 min of treatment every morning and evening for 4
      weeks. Endpoint estimates of phantom limb pain (PLP), stump pain, and physical
      function were registered 3 months after the treatment. Results All three
      interventions were associated with more that 50% reduction in visual analogue
      scale (VAS)-rated PLP and stump pain. Combined mirror-tactile treatment had a
      significantly better effect on PLP and stump pain than mirror or tactile therapy
      alone. The difference between the three treatment arms were however slight, and
      hardly of clinical relevance. After treatment, the reduction of pain remained
      unchanged for an observation period of 3 months. Conclusions The study documents
      that a 4-week treatment period with mirror and/or tactile therapy significantly
      reduces PLP and stump pain after trans-tibial amputations. Implications The
      article reports for the first time a randomized controlled trial of mirror
      therapy in a homogenous sample of persons with traumatic amputations. The
      findings are of special relevance to amputees in low-resource communities.

PMID- 30207290
TI  - ZnO-functionalized mesoporous inner-empty nanotheranostic platform: upconversion
      imaging guided chemotherapy with pH-triggered drug delivery.
AB  - Here we report a novel drug delivery system using mesoporous inner-empty
      upconversion microspheres carrying drugs with ZnO quantum dots (UCMPS@ZnO) acting
      as a 'door-keeper' for pH-triggered drug release. Compared to other upconversion
      drug delivery systems, it is smarter, simpler, more efficient and more
      biocompatible. In particular, the UCMPS@ZnO microspheres show low cytotoxicity,
      are simple to produce and have a high drug loading rate (15%). Promisingly, a
      mice treatment experiment demonstrated that the multifunctional nanoparticles
      have efficient inhibition of tumor growth after a 14-day treatment. This makes
      UCMPS@DOX-ZnO microspheres a promising theranostic candidate in cancer treatment
      and clinical trials.

PMID- 30207291
TI  - Self-assembly patterning of ultrafine zirconia nanocrystal films fabricated on
      chemically patterned templates.
AB  - Ultra-thin zirconia (ZrO2) nanocrystal films were fabricated by using a
      controlled dip-coating process. ZrO2 nanocrystals possess a cubic crystalline
      phase and large surface-to-volume area. The film composite with only several
      layers of nanocrystals were obtained by controlling the withdrawal speed and mass
      concentration of the colloidal solution. The optical properties of ZrO2
      nanocrystal films were accessed by UV-vis spectroscopy, which indicated the dense
      and uniform structure of the nanocrystal films. The high reflection index
      suggested that the films could be used in the reflection coating industry.
      Furthermore, a micro-pattern of self-assembled monolayers of silane molecular was
      used as a chemical mold for selective deposition of ZrO2 nanocrystals. As a
      result, a self-assembly patterning of ZrO2 nanocrystals with a neat edge was
      fabricated on silicon substrate. The low-cost fabricating method is compatible
      with conventional very-large-scale integration processes and can be extended to
      other kinds of nanocrystals.

PMID- 30207292
TI  - First-principles study of electronic properties of Cu doped Ag2S.
AB  - Using first-principles calculations based on density functional theory,
      electronic properties of Ag2S and Cu doped Ag2S were investigated. The calculated
      results show that Ag2S crystal is semiconductor with a band gap of 0.92 eV which
      is consistent with previous PBE calculation. Three possible Cu doping
      configurations are investigated: Cu substitution of Ag_I, Cu substitution of
      Ag_II, and interstitial Cu. It is found that interstitial Cu doping reduces the
      band gap as the Cu concentration increases, while for Ag_I and Ag_II substitution
      doping the band gap is not sensitive to the impurity concentration. The band gap
      reduction can mainly be attributed to the downward shift of the bottom of
      conduction band upon Cu interstitial doping. The reduction of the band gap for
      Ag2S with interstitial Cu doping is consistent with experimental absorption and
      fluorescence spectra, where a significant red-shift after Cu doping in Ag2S
      crystal is observed.

PMID- 30207293
TI  - EEG-based auditory attention detection: boundary conditions for background noise
      and speaker positions.
AB  - OBJECTIVE: A listener's neural responses can be decoded to identify the speaker
      the person is attending to in a cocktail party environment. Such auditory
      attention detection methods have the potential to provide noise suppression
      algorithms in hearing devices with information about the listener's attention. A
      challenge is the effect of noise and other acoustic conditions that can reduce
      the attention detection accuracy. Specifically, noise can impact the ability of
      the person to segregate the sound sources and perform selective attention, as
      well as the external signal processing necessary to decode the attention
      effectively. The aim of this work is to systematically analyze the effect of
      noise level and speaker position on attention decoding accuracy. APPROACH: 28
      subjects participated in the experiment. Auditory stimuli consisted of stories
      narrated by different speakers from two different locations, along with
      surrounding multi-talker background babble. EEG signals of the subjects were
      recorded while they focused on one story and ignored the other. The strength of
      the babble noise as well as the spatial separation between the two speakers were
      varied between presentations. Spatio-temporal decoders were trained for each
      subject, and applied to decode attention of the subjects from every 30 s segment
      of data. Behavioral speech recognition thresholds were obtained for the different
      speaker separations. MAIN RESULTS: Both the background noise level and the
      angular separation between speakers affected attention decoding accuracy.
      Remarkably, attention decoding performance was seen to increase with the
      inclusion of moderate background noise (versus no noise), while across the
      different noise conditions performance dropped significantly with increasing
      noise level. We also observed that decoding accuracy improved with increasing
      speaker separation, exhibiting the advantage of spatial release from masking.
      Furthermore, the effect of speaker separation on the decoding accuracy became
      stronger when the background noise level increased. A significant correlation
      between speech intelligibility and attention decoding accuracy was found across
      conditions. SIGNIFICANCE: This work shows how the background noise level and
      relative positions of competing talkers impact attention decoding accuracy. It
      indicates in which circumstances a neuro-steered noise suppression system may
      need to operate, in function of acoustic conditions. It also indicates the
      boundary conditions for the operation of EEG-based attention detection systems in
      neuro-steered hearing prostheses.

PMID- 30207294
TI  - Electronic structure and migration of interstitial hydrogen in the rutile phase
      of TiO2.
AB  - The formation and migration energies of interstitial hydrogen in rutile TiO2 are
      obtained from first principles calculations. The computational approach was based
      on density functional theory with a semilocal generalised-gradient approximation
      functional, supplemented with an on-site Hubbard term to account for correlation
      among the Ti 3d electrons. Charge-transition levels are calculated and compared
      to previous theoretical studies. The donor character of hydrogen is examined in
      depth, focusing in particular on the tendency to form polaron-like configurations
      with the unpaired electron trapped at nearby titanium ions. Distinct minimum
      energy paths of hydrogen migration and associated energy barriers were determined
      by the nudged elastic-band method. The present findings show clearly the strong
      anisotropy in the energy barriers for migration within the open c channels as
      opposed to migration crossing adjacent channels of the rutile lattice. For the
      rate-limiting step which leads to macroscopic diffusion along the c axis the
      corresponding rate and diffusion coefficient were also determined from transition
      state theory. The results are discussed in connection to existing measurements of
      hydrogen diffusion and recent findings from electron paramagnetic resonance,
      electron-nuclear double resonance and muonium spectroscopies that probed the
      spatial localization of the electron spin.

PMID- 30207295
TI  - Substrate elasticity dependent colony formation and cardiac differentiation of
      human induced pluripotent stem cells.
AB  - Substrate elasticity regulates cell functions including cell aggregation and stem
      cell differentiation. The ability to manufacture substrates of desired elasticity
      over a broad range is therefore crucial for both fundamental research and
      advanced applications. In this work, we developed a method to fabricate dense
      elastomer pillars of different heights on a rigid substrate, providing an
      effective elasticity ranging from 3 to 168 kPa. Assisted with an elastomer
      stencil of honeycomb pattern for cell seeding, we obtained uniform colonies of
      human induced pluripotent stem cells (hiPSCs) and differentiated cardiomyocytes
      on the pillar substrates of different modulus. Our results showed that the
      elasticity of substrates significantly affected the cell colony formation via
      governing the colony edge propagation. More importantly, the results demonstrated
      that an intermediate substrate elasticity of about 9 kPa is preferable to reach
      an embryoid-like aggregation and optimal for cardiac differentiation of hiPSCs.
      Overall, this work sheds new insights on the importance of substrate modulus on
      cell aggregation and stem cell differentiation as well as the manufacturing of
      culture substrates with desired elasticity.

PMID- 30207296
TI  - Balanced carrier injection of quantum dots light-emitting diodes: the case of
      interface barrier of bilayer ZnO electron transport layer.
AB  - Unbalanced carrier injection is one of the most important reasons for the
      efficiency roll-off in quantum dot light-emitting diodes. Reducing the electron
      injection can effectively balance the carrier transport and improve the
      optoelectronic performance of the device. In this work, a bilayer ZnO electron
      transport layer was fabricated by twice spin-coating and annealing methods. More
      than 60% of electrons are effectively blocked by the ZnO interface barrier
      compared with the standard device, resulting in increasing the maximum luminance
      of the device from 25 390 to 48 220 cd m-2 and the current efficiency from 1.5 to
      3.2 cd A-1.

PMID- 30207297
TI  - Vibrational dynamics within the embedded-atom-method formalism and the
      relationship to Born-von-Karman force constants.
AB  - We derive expressions for the dynamical matrix of a crystalline solid with total
      potential energy described by an embedded-atom-method (EAM) potential. We make no
      assumptions regarding the number of atoms per unit cell. These equations can be
      used for calculating both bulk phonon modes as well the modes of a slab of
      material, which is useful for the study of surface phonons. We further discuss
      simplifications that occur in cubic lattices with one atom per unit cell. The
      relationship of Born-von-Karman (BvK) force constants-which are readily extracted
      from experimental vibrational dispersion curves-to the EAM potential energy is
      discussed. In particular, we derive equations for BvK force constants for bcc and
      fcc lattices in terms of the functions that define an EAM model. The EAM-BvK
      relationship is useful for assessing the suitability of a particular EAM
      potential for describing vibrational spectra, which we illustrate using
      vibrational data from the bcc metals K and Fe and the fcc metal Au.

PMID- 30207298
TI  - The formation and stability of junctions in single-wall carbon nanotubes.
AB  - The structure and stability of molecular junctions, which connect two single-wall
      carbon nanotubes (SWCNTs) of different diameters and chiral angles, (n 1, m 1)-(n
      2, m 2), are systematically investigated by density functional tight binding
      calculations. More than 100 junctions, which connect well-aligned SWCNTs, were
      constructed and calculated. For a highly stable junction between two chiral (n 1,
      m 1) and (n 2, m 2) SWCNTs with opposite handedness, the number of pentagon
      heptagon (5/7) pairs required to build the junction can be denoted as ??n 2 - n
      1? - ?m 2 - m 1??+min{?n 2 - n 1?, ?m 2 - m 1?} with (n 2, m 2) rotating pi/3
      angle or not. While for a junction connected by two zigzag, armchair or two
      chiral SWCNTs with the same handedness, the number of 5/7 pairs is equal to ?n 1 
      n 2? + ?m 1 - m 2?. Similar to the formation energies of grain boundaries in
      graphene, the curve of the formation energies vs. chiral angle difference present
      an 'M' shape indicating the preference of ~30 degree junctions. Moreover, the
      formation energies of the zigzag-type and armchair-type junctions with zero
      misorientation angles are largely sensitive to the diameter difference of two sub
      SWCNTs.

PMID- 30207300
TI  - Coherent transport in Y-junction graphene waveguide.
AB  - We performed a series of theoretical transport studies on Y-branch electron
      waveguides which are embedded in mid-size armchair graphene nanoribbons. Non
      equilibrium Green's function with different approximations of tight-binding
      Hamiltonian has been employed. Using the first nearest hopping approximation, we
      observed very pronounced conductance quantization, the structure of which depends
      on geometrical design and shows a spacing of 4e 2/h, indicating the existence of
      valley degree of freedom. Moreover, by incorporating the third nearest
      approximation, we observed seminal plateaus deviated from multiples of 4e 2/h
      conductance, suggesting the lift of valley degeneracy. Finally, Quasi-one
      dimensional band structure calculations have been performed to study the
      availability of energy channels and the role of the major geometrical parameters
      on the transport.

PMID- 30207299
TI  - Magnetism of Bi2Se3 thin films with Eu-rich flat inclusions.
AB  - We report the results of experimental and theoretical studies of Eu-doped Bi2Se3
      thin films with extremely inhomogeneous distribution of magnetic component. The
      obtained electron microscopy images suggest that Eu atoms are concentrated within
      platelet-like nanoinclusions. The number of inclusions grows with the increase in
      Eu content, x. Moreover, at relatively high x values, the stacks of platelets
      (inclusions located one under another) become rather frequent. A comparative
      analysis of magnetic properties of the films under study reveals no pronounced
      changes of their temperature dependence with the increase in x, which, however,
      leads to the decrease in the average magnetic moment [Formula: see text] per Eu
      atom. A theoretical analysis of different mechanisms contributing to a possible
      magnetic ordering in the Eu-doped films demonstrates that at small distances
      (i.e. within a platelet) a dominant contribution is related to the RKKY
      interaction via electrons in the bulk, while the ordering at inter-platelet
      distances is governed by magnetic dipole-dipole interaction. The latter implies
      the antiferromagnetic ordering within the stacks of platelets explaining a drop
      of [Formula: see text] per Eu atom. We employ the model of a metallic spin glass
      to estimate the transition temperature, characterising the interaction within the
      ensemble of randomly distributed magnetic platelets. This estimate gives
      satisfactory agreement with the experiment, even if we take into account a finite
      film thickness, thus, neglecting the interaction anisotropy and including only
      the antiferromagnetism related to the stacking. While the overall contribution of
      interface Dirac electrons is damped in the systems under study, we argue that the
      obtained results can be used for the investigation of ultrathin films with
      analogous impurity profile, where this contribution should be clearly pronounced.

PMID- 30207301
TI  - Transformation of 2D group-III selenides to ultra-thin nitrides: enabling epitaxy
      on amorphous substrates.
AB  - The experimental realization of two-dimensional (2D) gallium nitride (GaN) has
      enabled the exploration of 2D nitride materials beyond boron nitride. Here we
      demonstrate one possible pathway to realizing ultra-thin nitride layers through a
      two-step process involving the synthesis of naturally layered, group-III
      chalcogenides (GIIIC) and subsequent annealing in ammonia (ammonolysis) that
      leads to an atomic-exchange of the chalcogen and nitrogen species in the 2D
      GIIICs. The effect of nitridation differs for gallium and indium selenide, where
      gallium selenide undergoes structural changes and eventual formation of ultra
      thin GaN, while indium selenide layers are primarily etched rather than
      transformed by nitridation. Further investigation of the resulting GaN films
      indicates that ultra-thin GaN layers grown on silicon dioxide act as effective
      'seed layers' for the growth of 3D GaN on amorphous substrates.

PMID- 30207302
TI  - Variational study of the interacting, spinless Su-Schrieffer-Heeger model.
AB  - We study the phase diagram and the total polarization distribution of the Su
      Schrieffer-Heeger model with nearest neighbor interaction in one dimension at
      half-filling. To obtain the ground state wave-function, we extend the Baeriswyl
      variational wave function to account for alternating hopping parameters. The
      ground state energies of the variational wave functions compare well to exact
      diagonalization results. For the case of uniform hopping for all bonds, where it
      is known that an ideal conductor to insulator transition takes place at finite
      interaction, we also find a transition at an interaction strength somewhat lower
      than the known value. The ideal conductor phase is a Fermi sea. The phase diagram
      in the whole parameter range shows a resemblance to the phase diagram of the Kane
      Mele-Hubbard model. We also calculate the gauge invariant cumulants corresponding
      to the polarization (Zak phase) and use these to reconstruct the distribution of
      the polarization. We calculate the reconstructed polarization distribution along
      a path in parameter space which connects two points with opposite polarization in
      two ways. In one case we cross the metallic phase line, in the other, we go
      through only insulating states. In the former case, the average polarization
      changes discontinuously after passing through the metallic phase line, while in
      the latter the distribution 'walks across' smoothly from one polarization to its
      opposite. This state of affairs suggests that the correlation acts to break the
      chiral symmetry of the Su-Schrieffer-Heeger model, in the same way as it happens
      when a Rice-Mele onsite potential is turned on.

PMID- 30207303
TI  - ZIF-derived carbons as highly efficient and stable ORR catalyst.
AB  - To develop highly efficient none-precious metal catalysts in lieu of Pt/C for
      catalyzing oxygen reduction reaction (ORR), ZIF-67 derived carbons are fabricated
      rationally in combination with reduced graphene oxide (rGO) integration and
      further KOH etching respectively. ZIF-C/rGO presents excellent ORR activity
      especially in alkali media with onset potential, half-wave potential and limited
      current density being 1.00 V, 0.87 V and 5.92 mA cm-2, respectively, which are
      close approaching or superior to those of commercial Pt/C. Although the ORR
      activity in acid media is still a little inferior to that of the Pt/C, the
      durability of ZIF-C/rGO is better in both alkali and acid electrolytes. Further
      KOH etching (ZIF-C/rGO-KOH) reduces active N sites and destroys the micropores
      with resulting in reduced ORR performances, though more mesopore Brunauer-Emmett
      Teller surface and volume are obtained. Through comparable study, huge
      performance enhancements form rGO integration is attributed to the attained
      higher charge transfer channels, more micropores with avoiding great losses of N
      and Co active sites can depress over polarization of electrolyte, aggregation of
      active components and collapsing of mass transport channels, on which the ORR
      activity is boosted to the extreme due to the resulted synergistic effect.

PMID- 30207304
TI  - Various responses of male pituitary-gonadal axis to different intensities of long
      term exercise: Role of expression of KNDYrelated genes.
AB  - The essential role of regular physical activity has been emphasized for
      maintaining a healthy life. However, unfortunately, during the last few decades,
      the lifestyle of people has led to a decrease in physical activity. Research
      studies have shown that exercise of different intensities is applied on
      reproductive performance indices, luteinizing hormone (LH) and testosterone (T),
      with different effects. Nevertheless, the molecular and cellular mechanisms
      underlying its function are not completely understood. Therefore, this study
      aimed to evaluate the role of kisspeptin, neurokinin-B and pro-dynorphin (KNDY)
      gene-expression changes located in the upstream of GnRH neurons in transferring
      the effects of different long-term exercise intensities on male reproductive
      axis. Twenty-one adult Wistar rats were randomly divided into control, 6-month
      regular moderate exercise (RME-6) and 6-month regular intensive exercise (RIE-6).
      In moderate and intensive exercise groups, rats were treated 5 days a week for 60
      min, at 22 and 35 m/min, respectively. Finally, the hypothalamic arcuate nucleus
      was isolated and the relative gene expression of kisspeptin (Kiss1), neurokinin-B
      (Nkb), pro-dynorphin (Pdyn) and gonadotropin-releasing hormone (Gnrh) genes were
      measured by realtime polymerase chain reaction method. The results showed that
      RIE-6 treatment decreased Gnrh and increased Pdyn mRNA levels in the arcuate
      nucleus. Furthermore, although RME-6 treatment decreased Nkb and increased Pdyn
      mRNA levels, the Gnrh mRNAwas not affected. Regarding the Gnrh mRNA levels and
      serum concentrations of reproductive indices (LH and T), moderate exercise did
      not impose harmful effects on the hypothalamic-pituitary-gonadal axis than
      intensive exercise. The different impacts of diverse long-term exercise
      intensities on the male pituitary-gonadal axis maybe relay by the various changes
      in hypothalamic Nkb and Pdyn gene expressions.

PMID- 30207305
TI  - Complex interplay of lesion-specific DNA repair enzyme on bistranded clustered
      DNA damage harboring Tg:G mismatch in nucleosome core particles.
AB  - 5,6-Dihydroxy-5,6-dihydrothymine (thymine glycol) and 7,8-dihydro-8-oxo-20
      deoxyguanosine (8-oxodG) are major DNA damage lesions produced by endogenous
      oxidative stress, as well as inflicted by carcinogens and ionizing radiation. The
      processing of Tg:G mismatch and 8-oxodG in close proximity of each other in a
      bistranded clustered environment in DNA oligomer duplexes as well as in a
      nucleosome core particle (NCP) model are reported here. The processing of the
      lesions was evaluated by purified enzyme cocktails of hNTH1 and hOGG1 as well as
      with a HeLa cell extract. Interestingly, the yield of double-strand breaks (DSBs)
      resulting from the processing of the bistranded lesions are appreciably lower
      when the DNA is treated with the HeLa cell extract compared with the relevant
      purified enzyme cocktail in both models. Clustered bistranded lesions become more
      repair refractive when reconstituted as an NCP. This indicates a complex
      interplay between the repair enzymes that influence the processing of the
      bistranded cluster damage positively to avoid the formation of DSBs under
      cellular conditions. In addition to position and orientation of the lesions, the
      type of the lesions in the cluster environment in DNA along with the relative
      abundance of the lesion-specific enzymes in the cells strongly prevents the
      processing of the oxidized nucleobases.

PMID- 30207306
TI  - Evaluation of metabolic changes induced by polyphenols in the crayfish Astacus
      leptodactylus by metabolomics using Fourier transformed infrared spectroscopy.
AB  - In the present study, the effects of polyphenols on the chemical composition of
      the hepatopancreas of the Astacus leptodactylus, a highly sought farmed crayfish,
      have been investigated by attenuated total reflectance-Fourier transform infrared
      (ATR-FTIR) spectroscopy. The hepatopancreas spectrum was quite complex and
      contained several peaks arising from the contribution of different functional
      groups belonging to protein, lipids and carbohydrates. The PCA statistical
      analysis revealed that there were significant differences between crayfish fed a
      diet without polyphenols and crayfish fed a diet containing polyphenols. Such
      differences indicated an increase in lipids and proteins in the hepatopancreas of
      polyphenol-fed crayfish. In conclusion, the analysis of the infrared spectral
      profile of the hepatopancreas of Astacus leptodactylus, allowed us to elucidate
      the changes in different biomolecules in response to polyphenol treatment, and
      confirms the suitability of ATR-FTIR spectral data to analyze diet-induced
      metabolic effects. These considerations, coupled with the small amount of sample
      and no preparation needed, make ATR-FTIR a useful tool for routine analyses where
      the metabolic impact of substances is investigated, especially with a large
      number of samples.

PMID- 30207307
TI  - PE-only/PE_PGRS proteins of Mycobacterium tuberculosis contain a conserved tetra
      peptide sequence DEVS/DXXS that is a potential caspase-3 cleavage motif.
AB  - Mycobacterium tuberculosis H37Rv is an intracellular pathogen responsible for
      causing tuberculosis in humans. The M. tuberculosis genome has been shown to
      contain a very large and unique family of PE proteins made of two sub-families:
      PE-only and PE_PGRS proteins. These two subtypes of proteins play a crucial role
      in the pathogenesis of the microbe. However, despite numerous investigations, the
      role of these proteins in disease development remains obscure. In this study,
      sequence analysis with a search for short conserved motifs revealed a conserved
      tetra-peptide motif DEVS/DXXS at the PE domain of almost every PE-only and
      PE_PGRS protein. The motif was found at a distance of 43-46 amino acids from the
      N-terminal of PE_PGRS proteins, and at a distance of between 35 and 82 amino
      acids of the PE-only proteins. As phosphorylation of the serine residue of this
      tetra-peptide could yield a motif similar to the caspase-3 binding recognition
      sequence DEVD/E, the region from a representative PE_PGRS protein (PE_PGRS45) was
      docked to human caspase-3. Strong interactions of only the protein containing the
      phosphorylated motif (DEVpS/DXXpS) to caspase-3 were observed. This suggested
      that the conserved DEVS/DXXS motif could have evolved for phosphorylation and
      subsequent recognition by caspase-3. These findings have important implications
      in unravelling the role of these PE proteins in mycobacterial infection.

PMID- 30207308
TI  - Functional characterisation of romeharsha and clint1 reaffirms the link between
      plasma membrane homeostasis, cell size maintenance and tissue homeostasis in
      developing zebrafish epidermis.
AB  - In vertebrates, early developing epidermis is a bilayered epithelium consisting
      of an outer periderm and the underlying basal epidermis. It eventually develops
      into a multi-layered epithelium. The mechanisms that control the architecture and
      homeostasis of early developing bilayered epidermis have remained poorly
      understood. Recently, we have shown that the function of Myosin Vb, an actin
      based molecular motor, is essential in peridermal cells for maintenance of plasma
      membrane homeostasis. Furthermore, our analyses of the goosepimples/myosin Vb
      mutant unravelled a direct link between plasma membrane homeostasis, cell size
      maintenance and tissue homeostasis in the developing epidermis. However, it
      remained unclear whether this link is specific to myosin Vb mutant or this is a
      general principle. Here we have identified two more genetic conditions,
      romeharsha mutant and clint1 knockdown, in which membrane homeostasis is
      perturbed, as evident by increased endocytosis and accumulation of lysosomes. As
      a consequence, peridermal cells exhibit smaller size and increased proliferation.
      We further show that decreasing endocytosis in romeharsha mutant and clint1
      morphants rescues or mitigates the effect on cell size, cell proliferation and
      morphological phenotype. Our data confirms generality of the principle by
      reaffirming the causal link between plasma membrane homeostasis, cell size
      maintenance and tissue homeostasis.

PMID- 30207309
TI  - Little imaginal discs, a Trithorax group member, is a constituent of nuclear
      matrix of Drosophila melanogaster embryos.
AB  - Nuclear Matrix (NuMat) is the structural and functional framework of the nucleus.
      It has been shown that attachment of chromatin to NuMat brings significant
      regulation of the transcriptional activity of particular genes; however, key
      components of NuMat involved in this process remain elusive. We have identified
      Lid (Little imaginal discs) as one of the components of NuMat. It belongs to the
      TrxG group of proteins involved in activation of important developmental genes.
      However, unlike other activator proteins of TrxG, Lid is a Jumonji protein
      involved in H3K4me3 demethylation. Here, we report the association of Lid and its
      various domains with NuMat which implicates its structural role in chromatin
      organization and epigenetic basis of cellular memory. We have found that both N
      and C terminal regions of this protein are capable of associating with NuMat. We
      have further mapped the association of individual domains and found that, PHD,
      ARID and JmjC domains can associate with NuMat individually. Moreover, deletion
      of N-terminal PHD finger does not alter Lid's NuMat association implying that
      although it is sufficient, yet, it is not necessary for Lid's structural role in
      NuMat. Based on our findings, we hypothesize that C terminal region of Lid which
      contains PHD fingers might be responsible for its NuMat association via protein
      DNA interactions. However, for the N terminal region harboring both a PHD and an
      ARID finger, Lid anchors to the NuMat via both protein-protein and protein-DNA
      interactions. The association of JmjC domain with NuMat is the first report of
      the association of a demethylase domain with NuMat suggesting that Lid, a
      demethylase, being part of NuMat might be involved in regulating the chromatin
      dynamics via its NuMat association.

PMID- 30207310
TI  - An exploration of microbial and associated functional diversity in the OMZ and
      non-OMZ areas in the Bay of Bengal.
AB  - Depletion of oxygen in certain marine areas creates oxygen minimum zones (OMZs),
      which can alter the species composition and abundance. We have carried out high
      throughput 16S rRNA gene amplicon profiling from the Bay of Bengal (BOB) OMZ and
      non-OMZ areas. Typically, a total of 35 families of micro-organisms were
      identified as biomarkers for OMZ and non-OMZ regions in the BOB. Our analysis has
      identified families Pseudoalteromonadaceae, OM60 and Synechococcaceae to be
      abundant in oxygenated water, whereas organisms belonging to families
      Pelagibacteraceae and Caulobacteraceae, which are involved in sulphur and
      nitrogen metabolism, were prominent in the OMZ areas. Predictive functional
      analysis for these identified bacteria clearly that suggested an abundance of
      microbes with assimilatory sulphurreducing genes (cysl and csH) in the non-OMZ,
      while bacteria involved in dissimilatory sulphate reduction (known to carry aprA
      and aprB genes) were enriched in the OMZ areas. Comparative analysis with OMZ
      areas from Peru and Chile revealed that OMZ areas in the BOB are characterized by
      specific and distinctive bacterial diversity. Overall, the current analysis
      provides valuable documentation about the bacterial populations and their
      characteristics, which can generate pointers for their functional significance in
      the BOB.

PMID- 30207311
TI  - In vitro preconditioning of insulin-producing cells with growth factors improves
      their survival and ability to release insulin.
AB  - Glucose-induced oxidative stress in the diabetic pancreas directly affects
      viability and the consequent therapeutic outcome of transplanted stem cells.
      Pretreatment of stem cells with growth factors induces tolerance in them against
      various stresses (hypoxia, thermal or hyperglycaemic). This study investigated
      the effect of pretreatment on insulin-producing cells (IPCs) differentiated from
      adipose-derived mesenchymal stem cells (ADMSCs), with a combination of stromal
      cell-derived factor 1 alpha (SDF1 alpha) and basic fibroblast growth factor
      (bFGF) against hyperglycaemic stress (17 or 33 mM glucose). The results showed
      that IPCs pretreated with a combination of SDF1alpha and bFGF exhibited maximally
      alleviated apoptosis, senescence and cell damage with a concomitantly increased
      release of insulin, enhanced cell proliferation and greater upregulation of
      Insulin 1, Insulin 2, Ngn3, Pdx1 and Nkx6.2 when stressed with 33 mM glucose.
      These findings may offer an improved therapeutic outcome for the treatment of
      diabetes.

PMID- 30207312
TI  - Construction, expression and functional analysis of anti-B7-H4- scFv-CH3
      recombinant antibody.
AB  - The B7-H4 molecule, a unique negative regulator of T lymphocytes which is
      overexpressed on the surface of various tumor cells, is a particularly important
      target candidate for tumor therapy because it can be blocked with anti-B7-H4
      antibodies to inhibit the B7-H4 signaling pathway. Our previous work established
      an anti-B7-H4 single-chain variable fragment (scFv) library, so we have now
      amplified the genes encoding anti-B7-H4-scFv and human IgG1 CH3 and ligated them
      by overlap extension PCR to obtain a recombinant gene. After sequencing, the gene
      was cloned into the expression vector pET43.1a and expression was induced in E.
      coli BL21 (DE3) by isopropyl-beta-D-1-thiogalactopyranoside (IPTG). The protein
      was purified on a nickel-nitrilotriacetic acid (Ni-NTA) resin column and its
      antigen specificity and affinity were examined by ELISA and western blotting. We
      also established a Lewis lung cancer model in C57BL/6 mice to further identify
      the biological function of the scFv protein in vivo. The results showed that
      tumor volume, body weight and necrotic tissues in the control group were
      significantly greater than in the experimental group, indicating that selected
      scFvs had good biological activity and could inhibit tumor growth in tumor
      bearing mice. Our work thus offers a new approach for the development of cancer
      targeted therapy.

PMID- 30207313
TI  - Fine nanostructural variation in the wing pattern of a moth Chiasmia eleonora
      Cramer (1780).
AB  - Butterflies and moths possess diverse patterns on their wings. Butterflies employ
      miscellaneous colour in the wings whereas moths use a combination of dull colours
      like white, grey, brown and black for the patterning of their wings. The
      exception is some of the toxic diurnal moths which possess bright wing
      colouration. Moths possess an obscure pattern in the dorsal part of the wings
      which may be a line, zigzag or swirl. Such patterns help in camouflage during
      resting period. Thus, the dorsal wing pattern of the moth is used for both intra-
      as well as inter-specific signal communication. Chiasmia eleonora is a nocturnal
      moth of greyish black colouration. The dorsal hindwing possesses yellow and black
      colour patches. A whitecoloured oblique line crosses both left and right fore-
      and hindwings to form a V-shaped pattern across the dorsal wing. This V-shaped
      pattern possesses a UV signal. Closer to the body, the colour appears darker,
      which fades towards the margin. The fine nanostructural variation is observed
      throughout the wings. This study elucidates the wing pattern of the geometrid
      moth C. eleonora using high-resolution microscopy techniques that has not been
      described in previous studies.

PMID- 30207314
TI  - Posttranscriptional regulation of cyclin D1 by ARE-binding proteins AUF1 and HuR
      in cycling myoblasts.
AB  - RNA binding proteins (RBPs) can regulate the stability and/or translatability of
      messengerRNAs (mRNAs) through interactions with their 30-untranslated regions.
      However, individual mRNAs may be regulated simultaneously or successively by more
      than one RBP, as well as by Argonaute (AGO)-bound miRNAs; the coordination of
      these various influences on an individual mRNA is therefore complex and not well
      studied. In this report we examine the roles of two RBPs that bind to AU-rich
      elements (ARE) - AUF1 and HuR - in the stability and translation of cyclin D1
      (Ccnd1) mRNA in rat myoblasts transiting the G phase of the cell cycle, and their
      interactions with miRNAs. Knockdown (KD) of AUF1 resulted in (1) transient
      upregulation of the mRNA level as well as an advancement of translation onset
      time (TOT) from 6 to 5 h post-serum addition, (2) loss of miRNA loading on AGO1
      and AGO2 and (3) reduction in the level of AGO-1 and AGO-2 bound mRNA. In
      contrast, KD of HuR had no effect on the mRNA level, or on the AGO-mRNA
      complexes, but delayed TOT by 1 h independent of miRNA let-7. Thus the dynamics
      of RBP-mRNA binding and -RBP-AGO-miRNA interactions are coordinated to fine tune
      the expression of Ccnd1 in the G1 phase.

PMID- 30207316
TI  - Antibacterial properties of human beta defensin-3 derivative: CHRG01.
AB  - Antibiotic resistance in bacteria is a major health concern. Antimicrobial
      peptides (AMPs) are a class of peptides that are efficient in killing most
      microbes yet development of resistance to AMPs is rare. However, complex
      secondary and tertiary structures and difficulties in isolating AMPs have limited
      their use as antibiotics. It has been demonstrated earlier that small peptides
      derived from human beta defensin-3 (HBD-3) also show antibacterial activity.
      Here, we perform a detailed characterization of the antibacterial activity of one
      such derivative: CHRG01. While HBD-3 has 45 amino acids with three disulphide
      bonds and a beta-sheet folded structure, CHRG01 has only 14 amino acids with the
      cysteine residues replaced by serine. The antibacterial nature of CHRG01 was
      studied using scanning electron microscopy (SEM), confocal microscopy, circular
      dichroism (CD) and small-angle X-ray scattering (SAXS). CD data show that CHRG01
      is random coiled in solution. SEM and confocal studies show that the mode of
      action of CHRG01 is pore forming. SAXS studies show that CHRG01 induces a
      negative Gaussian curvature, the type of curvature needed for pore formation. The
      above results show that CHRG01, a small peptide without any complex structure, is
      capable of killing bacteria by permeabilizing their outer membranes.

PMID- 30207315
TI  - A putative NEM1 homologue regulates lipid droplet biogenesis via PAH1 in
      Tetrahymena thermophila.
AB  - Nuclear envelope morphology protein 1 (NEM1) along with a phosphatidate
      phosphatase (PAH1) regulates lipid homeostasis and membrane biogenesis in yeast
      and mammals. We investigated four putative NEM1 homologues (TtNEM1A, TtNEM1B,
      TtNEM1C and TtNEM1D) in the Tetrahymena thermophila genome. Disruption of
      TtNEM1B, TtNEM1C or TtNEM1D did not compromise normal cell growth. In contrast,
      we were unable to generate knockout strain of TtNEM1A under the same conditions,
      indicating that TtNEM1A is essential for Tetrahymena growth. Interestingly, loss
      of TtNEM1B but not TtNEM1C or TtNEM1D caused a reduction in lipid droplet number.
      Similar to yeast and mammals, TtNem1B of Tetrahymena exerts its function via
      Pah1, since we found that PAH1 overexpression rescued loss of Nem1 function.
      However, unlike NEM1 in other organisms, TtNEM1B does not regulate ER/nuclear
      morphology. Similarly, neither TtNEM1C nor TtNEM1D is required to maintain normal
      ER morphology. While Tetrahymena PAH1 was shown to functionally replace yeast
      PAH1 earlier, we observed that Tetrahymena NEM1 homologues did not functionally
      replace yeast NEM1. Overall, our results suggest the presence of a conserved
      cascade for regulation of lipid homeostasis and membrane biogenesis in
      Tetrahymena. Our results also suggest a Nem1-independent function of Pah1 in the
      regulation of ER morphology in Tetrahymena.

PMID- 30207317
TI  - Fast Fourier infrared spectroscopy to characterize the biochemical composition in
      diatoms.
AB  - Diatoms are photosynthetic unicellular microalgae and are nature's hidden source
      of several biosynthetic metabolites with their use in biofuel, food and drug
      industries. They mainly contain various lipids, sterols, isoprenoids and toxins
      with their use in apoptotic, fertility controlling and cancer drugs. Chemical
      studies on diatoms are limited due to various limitations such as variation of
      nutrients, contaminants and change in seasonal factors in the environment. To
      overcome these limitations, we obtained axenic cultures of 12 fresh-water diatom
      strains on the 22nd day of inoculation having a dry weight of 1 mg each and
      performed their Fourier transform infrared (FTIR) study for the detection of
      functional groups responsible for their chemical moiety. The spectral mapping
      showed a varied level of polyunsaturated fatty acids, amides, amines, ketone
      bodies and esters for their applications in various pharmacological, food and
      biofuel industries in the exponential phase of their growth in f/2 media. The
      FTIR study of the 12 diatom strains showed various similarities in the form of
      some common peak patterns ranging from 3000 to 3600 cm-1 for vO-H absorption. The
      symmetric stretching vibration frequency of Diadesmis confervaceae (V2) type
      species showed different behaviour than others in the spectral region starting
      from 1600 to 1700 cm-1. The absorption between 1500 and 1575 cm-1 reflects the
      presence of the -N-H group. Infrared (IR) absorptions falling between 1600 and
      1700 cm-1 reflect the presence of amide's vC=O in all species. Placoneis
      elginensis (V8) type species showed an additional absorption band which is
      centred around 1735-1750 cm-1 which perhaps reflects the presence of ester's
      vC=O. Diadesmis confervaceae (V2), Nitzschia palea (V4), Placoneis elginensis
      (V8), Nitzschia palea var. debilis (V6), Nitzschia inconspicua (V10), Gomphonema
      parvulum (V11) and Sellaphora (V12) showed distinct structural features with
      important key functionalities that can make them essential drug markers in the
      pharmaceutical industry.

PMID- 30207318
TI  - Ambient ionization mass spectrometry imaging for disease diagnosis: Excitements
      and challenges.
AB  - Tissue analysis in histology is extremely important and also considered to be a
      gold standard to diagnose and prognosticate several diseases including cancer.
      Intraoperative evaluation of surgical margin of tumor also relies on frozen
      section histopathology, which is time consuming, challenging and often
      subjective. Recent development in the ambient ionization mass spectrometry
      imaging (MSI) technique has enabled us to simultaneously visualize hundreds to
      thousands of molecules (ion images) in the biopsy specimen, which are strikingly
      different and more powerful than the single optical tissue image analysis in
      conventional histopathology. This paper will highlight the emergence of the
      desorption electrospray ionization MSI (DESI-MSI) technique, which is label-free,
      requires minimal or no sample preparation and operates under ambient conditions.
      DESI-MSI can record ion images of lipid/metabolite distributions on biopsy
      specimens, providing a wealth of diagnostic information based on differential
      distributions of these molecular species in healthy and unhealthy tissues.
      Remarkable success of this technology in rapidly evaluating the cancer margin
      intraoperatively with very high accuracy also promises to bring this imaging
      technique from bench to bedside.

PMID- 30207319
TI  - Role of miRNAs in hypoxia-related disorders.
AB  - Hypoxia is a complex pathophysiological condition. The physiological and
      molecular responses to this stress have been extensively studied. However, the
      management of its ill effects still poses a challenge to clinicians. MicroRNAs
      (miRNAs) are short non-coding RNA molecules that control post-transcriptional
      gene expression. The regulatory role of miRNAs in hypoxic environments has been
      studied in many hypoxia-related disorders, however a comprehensive compilation
      and analysis of all data and the significance of miRNAs in hypoxia adaption is
      still lacking. This review summarizes the miRNAs related to various hypoxia
      related disorders and highlights the computational approaches to study them. This
      would help in designing novel strategies toward efficient management of hypoxia
      related disorders.

PMID- 30207320
TI  - Significance of avian linker histone (H1) polymorphic variation.
AB  - Most of avian histone H1 non-allelic subtypes, i.e. eight out of nine, show
      polymorphic heterogeneity manifested by the presence of two or three allelic
      variants formed as a result of amino acid deletion and substitution. In addition,
      some of histone H1 non-allelic subtypes exhibit various allelic complements in
      different bird species leading to the widening of a whole pool of histone H1
      polymorphic variation. A wide range of histone H1 heterogeneity may indicate that
      the polymorphic variants can individually modulate some histone H1-dependent
      cellular processes by showing allele-specific influence on chromatin organization
      and function. Although, the exact way of avian histone H1 allelic variants'
      activity is not known, their structural separateness inferred from biochemical
      experiments and relationship with some characteristics of organism functioning
      disclosed in the genetic studies seem to confirm their importance. The aim of
      this review is to characterize the molecular origin of histone H1 polymorphisms
      and draw attention to the link between the histone H1 polymorphic variants and
      avian organismal features related to the physiological effects of bird
      individuals' living in the natural and breeding populations.

PMID- 30207321
TI  - Role of green fluorescent proteins and their variants in development of FRET
      based sensors.
AB  - Since the last decade, a lot of advancement has been made to understand
      biological processes involving complex intracellular pathways. The major
      challenge faced was monitoring and trafficking of metabolites in real time.
      Although a range of quantitative and imaging techniques have been developed so
      far, the discovery of green fluorescent proteins (GFPs) has revolutionized the
      advancement in the field of metabolomics. GFPs and their variants have enabled
      researchers to 'paint' a wide range of biological molecules. Fluorescence
      resonance energy transfer (FRET)-based genetically encoded sensors is a promising
      technology to decipher the real-time monitoring of the cellular events inside
      living cells. GFPs and their variants, due to their intrinsic fluorescence
      properties, are extensively being used nowadays in cell-based assays. This review
      focuses on structure and function of GFP and its derivatives, mechanism emission
      and their use in the development of FRET-based sensors for metabolites.

PMID- 30207324
TI  - Correction to: Interdependence of laforin and malin proteins for their stability
      and functions could underlie the molecular basis of locus heterogeneity in Lafora
      disease.
AB  - Correction to: J. Biosci. 40(5), December 2015, 863-871
      https://doi.org/10.1007/s12038-015-9570-0 The image of anti-Myc blot of figure 2C
      (third panel; Malin-Myc [C26S]) was inadvertently used once again for the c
      tubulin loading control of figure 2B. The revised figure 2B with the correct
      image of the c-tubulin loading control is given below. The interpretation and
      conclusion provided in the article do not change because of the correction.

PMID- 30207322
TI  - HTLV-1: A real pathogen or a runaway guest of a diseased cell?
AB  - The human T-cell lymphotropic virus type 1 (HTLV-1) is a deltaretrovirus claimed
      to be aetiologically linked to the adult T-cell leukaemia/lymphoma (ATLL) and
      associated myelopathy/tropical spastic paraparesis (HAM/TSP) besides other minor
      pathologies. HTLV-1 infection is worldwide distributed, despite its heterogeneous
      prevalence. Environmental factors and host-genetic background are very likely to
      determine the epidemiological profile of HTLV-1 prevalence and related disease
      confinement in distinct human ethnic populations and geographical coordinates,
      which raises the question if the virus is a real pathogen or a runaway well
      organized packed genome of a burden host cell near death process. New
      methodological approaches need to be proposed and applied in order to prove or
      discard the hypotheses emerged in the present review.

PMID- 30207325
TI  - Plasmacytoma of the mesentery.
AB  - Extramedullary plasmacytoma represents 3%-5% of all plasma cell neoplasms.
      Plasmacytomas of the mesentery are extremely rare. We report the case of a 56
      year-old man who presented with an abdominal mass and was diagnosed to have
      plasmacytoma of the mesentery. A literature review was also conducted on
      publications pertaining to solitary mesenteric plasmacytomas. These patients
      present late by which time the abdominal mass has reached a significant size.
      Radiation as a modality for local control has a limited role in treating
      mesenteric plasmacytomas. Surgery is the preferred modality for local control.
      Patients must be kept on a regular follow-up as there is a risk of transformation
      to multiple myeloma.

PMID- 30207323
TI  - Recent developments in nucleobase cation symporter-1 (NCS1) family transport
      proteins from bacteria, archaea, fungi and plants.
AB  - The nucleobase cation symporter-1 (NCS1) family of secondary active transport
      proteins comprises over 2500 sequenced members from bacteria, archaea, fungi and
      plants. NCS1 proteins use a proton or sodium gradient to drive inward cellular
      transport of purine and pyrimidine nucleobases and nucleosides, hydantoins and
      related compounds. The structural organization, substrate binding residues and
      molecular mechanism of NCS1 proteins are defined by crystal structures of sodium
      coupled hydantoin transporter, Mhp1. Plant proteins are most closely related to
      bacterial/archaeal proteins and the distinct Fur-type and Fcy-type fungal
      proteins and plant proteins originated through independent horizontal transfers
      from prokaryotes. Analyses of 25 experimentally characterized proteins reveal
      high substrate specificity in bacterial proteins, distinct non-overlapping
      specificities in Fur-type and Fcy-type fungal proteins and broad specificity in
      plant proteins. Possible structural explanations are identified for differences
      in substrate specificity between bacterial proteins, whilst specificities of
      other proteins cannot be predicted by simple sequence comparisons. Specificity
      appears to be species specific and determined by combinations of effects dictated
      by multiple residues in the major substrate binding site and gating domains. This
      is an exploratory research review of evolutionary relationships, function and
      structural organization, molecular mechanism and origins of substrate specificity
      in NCS1 proteins and avenues of future direction.

PMID- 30207326
TI  - Prevention of Strongyloides stercoralis hyperinfection in leprosy patients on
      long-term steroid therapy.

PMID- 30207327
TI  - Rational use of laboratory test.

PMID- 30207328
TI  - Real-World Study of the Incidence, Risk Factors, and Prognostic Factors
      Associated with Bone Metastases in Women with Uterine Cervical Cancer Using
      Surveillance, Epidemiology, and End Results (SEER) Data Analysis.
AB  - BACKGROUND The aims of this study were to investigate the incidence and risk
      factors for the development of bone metastases and prognosis in women with cancer
      of the uterine cervix using database analysis. MATERIAL AND METHODS The National
      Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER)
      database was analyzed for the incidence and survival rates of women diagnosed
      with uterine cervical cancer in the United States between 2010-2015. Multivariate
      logistic regression analysis identified risk factors for bone metastases. Kaplan
      Meier analysis estimated the overall survival. Proportional hazard regression
      analysis estimated prognostic factors associated with bone metastases. RESULTS
      There were 19,363 women with uterine cervical cancer, and 469 women were
      diagnosed with bone metastases on initial diagnosis (2.42%). Increased T-stage, N
      stage, non-squamous and non-adenocarcinoma histology, high-grade tumors, and the
      presence of lung, liver, and brain metastases were all significantly associated
      with early bone metastases. There were 364 patients with cervical cancer and bone
      metastases on initial diagnosis who were followed-up for at least one year.
      Multivariate Cox regression analysis showed that unmarried status and lung,
      liver, and brain metastases were significantly associated with reduced overall
      survival. No other significant risk or prognostic associations were found.
      CONCLUSIONS SEER data analysis showed that women with uterine cervical cancer had
      some standard risk factors associated with bone metastases, and with prognosis,
      but a heterogeneous group of risk factors was also present. The findings of this
      study may have clinical application in screening for bone metastases in women
      with cervical cancer.

PMID- 30207329
TI  - Design of a simple paper-based colorimetric biosensor using polydiacetylene
      liposomes for neomycin detection.
AB  - We developed a paper-based analytical device (MUPAD) combined with self-signaling
      polydiacetylene (PDA) liposomes for convenient visual neomycin detection. The
      simple dot array type of MUPAD was fabricated by the wax printing technique, and
      the PDA liposomes in the aqueous solution were facilely immobilized onto the
      hydrophilic dot region of the paper substrate. We found that, when the PDA
      liposomes were inserted to the paper matrix, the stability of the PDA liposomes
      can be significantly enhanced by adding a hydrophilic reagent such as polyvinyl
      alcohol and glycerol to the liposome solution. In particular, polyvinyl alcohol
      (PVA) provides the best stabilization among the various hydrophilic reagents
      tested in this contribution, and the enhanced stability sharply increased the
      sensitivity of the PDA liposomes in the paper matrix. Based on the above results,
      we successfully detected neomycin through both naked-eye observation and
      fluorescence measurement of PDA signals. The detection limit was 1 ppm and was
      selective to non-aminoglycoside antibiotics.

PMID- 30207330
TI  - Direct, uncorrected, molecule-free analysis of 236U from uranium-bearing
      particles with NAUTILUS: a new kind of mass spectrometer.
AB  - We demonstrate use of the Naval Ultra-Trace Isotope Laboratory's Universal
      Spectrometer (NAUTILUS) at the U.S. Naval Research Laboratory (NRL) to measure
      236U directly from uranium-bearing particles free from molecular isobaric
      interferences. Particles with 235U enrichments in the range of 0.32% to 3.28% and
      236U enrichments from no enrichment to 0.015% provided by the International
      Atomic Energy Agency (IAEA) were analyzed directly using the NAUTILUS. We report
      the experimental data here without correcting for molecular hydrides and/or
      applying any other background subtractions. The results from all samples agreed
      with the certified values within standard error save for the 236U composition of
      the IRMM 023, which suffered from a combination of insufficient particle sizes
      and sub-MUmol mol-1 236U concentrations. We were able, however, to directly
      measure as low as three MUmol mol-1 of 236U in individual particles regardless of
      the 235U concentration. Our results are comparable with Large Geometry Secondary
      Ion Mass Spectrometry (LG-SIMS) and serve as baseline for a more comprehensive
      comparison between LG-SIMS and the NAUTILUS in the future. Moreover, we
      demonstrate the ability of the NAUTILUS to generate raster ion images with the
      same ease as traditional LG-SIMS instruments. By combining our ability to measure
      236U directly with raster ion imaging, we were able to detect a low intensity,
      small uranium-bearing particle in the presence of high molecular backgrounds for
      a non-ideal sample. This discovery could lead to more targeted and, therefore,
      less time intensive particle screening methodologies.

PMID- 30207331
TI  - Electrochemical detection of Alzheimer's disease related substances in biofluids
      by silica nanochannel membrane modified glassy carbon electrodes.
AB  - Alzheimer's disease (AD) affects middle- and old-age populations, and causes loss
      of brain weight, degradation of brain functions and memory loss. So the fast and
      accurate detection of AD related markers is highly important in diagnosis. We
      report in this work the detection of Cu2+ and dopamine (DA), which are markers
      related to AD, by direct electrochemistry (DEC) and electrochemiluminescence
      (ECL) using a silica nanochannel membrane modified glassy carbon electrode
      (SNM/GCE). By DEC, the detection of both Cu2+ and DA in buffer solutions was
      achieved with a wide linear range and a low limit of detection (LOD). The
      determination of DA was also achieved in terms of its quenching effect on the ECL
      of the tris(2,2'-bipyridyl)ruthenium(ii)/tri-n-propylamine co-reactant system in
      both intensity and image modes, yielding a particularly high sensitivity in the
      former case. In comparison with a bare GCE, the analytical sensitivity and
      selectivity of the SNM/GCE were superior, most likely due to the analyte pre
      concentration and permselective effects of the SNM. Moreover, given that the SNM
      consists of perpendicular channels with a negatively charged surface, high
      channel density (ca. 7.5 * 1012 cm-2) and uniform size (ca. 2.3 nm in diameter),
      it displays a high molecular permeability and meanwhile a high selectivity in
      terms of molecular size and charge. So the SNM/GCE exhibited an excellent anti
      fouling ability in biofluids, such as human blood and artificial cerebrospinal
      fluid, suppressing effectively the interference of coexisting substances (such as
      cells, proteins, and other big and small molecules) and providing excellent
      signal stability.

PMID- 30207332
TI  - "Fix and assay": separating in-cellulo sphingolipid reactions from analytical
      assay in time and space using an aldehyde-based fixative.
AB  - Chemical cytometry using capillary electrophoresis (CE) is a powerful tool for
      measuring single-cell enzyme activity. However, these measurements are often
      confounding as dynamic processes within cells rapidly change depending on
      environment, meaning that cell handling, transport, and storage can affect
      signaling pathways and alter results. To meet these challenges, we describe a
      method utilizing aldehyde fixation to simultaneously terminate cellular reactions
      across a population, freezing reaction results in time prior to analytical
      analysis. Fluorescent sphingosine was loaded into cells of different lineages
      (leukemia and lymphoma cell lines and primary leukemia cells) and allowed to
      react before fixing. The remaining sphingosine and any products formed were then
      quantified with chemical cytometry utilizing CE. When cells were loaded with
      sphingosine followed by glyoxal fixation and immediate analysis, 55 +/- 5% of
      lipid was recoverable compared to an unfixed control. Storage of fixed cells for
      24 h showed no statistical differences in total amount of recoverable
      sphingolipid compared to samples analyzed immediately after fixation-though there
      was a difference in recovery of low-abundance products. Sphingosine kinase
      activity decreased in response to inhibitor treatment compared to treatment with
      a DMSO vehicle (21 +/- 3% product formed in inhibitor-treated cells vs. 57 +/- 2%
      in control cells), which was mirrored in single-cell measurements. This "fix and
      assay" strategy enables measurement of sphingosine kinase activity in single
      cells followed by subsequent analytical assay separated in space and time from
      reaction initiation, enabling greater temporal control over intracellular
      reactions and improving future compatibility with clinical workflow.

PMID- 30207333
TI  - Raman spectroscopy as a tool for tracking cyclopropane fatty acids in genetically
      engineered Saccharomyces cerevisiae.
AB  - Cyclopropane fatty acids (CFAs) are a group of lipids with unique physical and
      chemical properties between those of saturated and monounsaturated fatty acids.
      The distinctive physicochemical characteristics of CFAs (e.g. oxidative
      stability, self-polymerization at high temperatures, etc.) results from the
      presence of a cyclopropane ring within their structure making them highly useful
      in industrial applications. CFAs are present in several species of plants and
      bacteria and are typically detected with standard lipid profiling techniques,
      such as gas or liquid chromatography. In this work we investigated several
      strains of S. cerevisiae, genetically modified to introduce the production of
      CFAs, in comparison to control strain using confocal Raman spectroscopy (CRS).
      The aim of our work was to demonstrate the potential of CRS not only to detect
      changes introduced due to the CFAs presence, but also to track CFAs within the
      cells. We present for the first time Raman and IR spectra of CFA standard (cis
      9,10-methyleneoctadecanoic acid), completed with quantum chemical calculations
      and band assignment. We identified marker bands of CFA (e.g. 2992, 1222, 942 cm
      1) attributed to the vibrations of the cyclopropyl ring. Furthermore, we analysed
      lipid bodies (LBs) from modified and control yeast using CRS imaging and
      identified multiple changes in size, number and composition of LBs from
      engineered strains. We observed a significant reduction in the degree of
      unsaturation of LBs using the ratio of bands located at 1660 cm-1 (nu(C[double
      bond, length as m-dash]C)) and 1448 cm-1 (delta(CH2)) in the modified cell lines.
      In addition, we were able to detect the presence of CFAs in LBs, using the
      established marker bands. CRS shows tremendous potential as technique to identify
      CFAs in lipid bodies providing a new way to track lipid production in genetically
      modified single yeast cells.

PMID- 30207334
TI  - A new approach to find biomarkers in chronic fatigue syndrome/myalgic
      encephalomyelitis (CFS/ME) by single-cell Raman micro-spectroscopy.
AB  - Chronic fatigue syndrome (CFS), also called myalgic encephalomyelitis (ME), is a
      debilitating disorder characterized by physical and mental exhaustion.
      Mitochondrial and energetic dysfunction has been investigated in CFS patients due
      to a hallmark relationship with fatigue; however, no consistent conclusion has
      yet been achieved. Single-cell Raman spectra (SCRS) are label-free biochemical
      profiles, indicating phenotypic fingerprints of single cells. In this study, we
      applied a new approach using single-cell Raman microspectroscopy (SCRM) to
      examine rho0 cells that lack mitochondrial DNA (mtDNA), and peripheral blood
      mononuclear cells (PBMCs) from CFS patients and healthy controls. The
      experimental results show that Raman bands associated with phenylalanine in rho0
      cells and CFS patient PBMCs were significantly higher than those of the wild-type
      model and healthy controls. As similar changes were observed in the rho0 cell
      model with a known deficiency in the mitochondrial respiratory chain as well as
      in CFS patients, our results suggest that the increase in cellular phenylalanine
      may be related to mitochondrial/energetic dysfunction in both systems.
      Interestingly, phenylalanine can be used as a potential biomarker for the
      diagnosis of CFS by SCRM. A machine learning classification model achieved an
      accuracy rate of 98% correctly assigning Raman spectra to either the CFS group or
      the control group. SCRM combined with a machine learning algorithm therefore has
      the potential to become a diagnostic tool for CFS.

PMID- 30207335
TI  - Electronic structure, optical and photocatalytic performance of SiC-MX2 (M = Mo,
      W and X = S, Se) van der Waals heterostructures.
AB  - The stacking of monolayers in the form of van der Waals heterostructures is a
      useful strategy for band gap engineering and the control of dynamics of excitons
      for potential nano-electronic devices. We performed first-principles calculations
      to investigate the structural, electronic, optical and photocatalytic properties
      of the SiC-MX2 (M = Mo, W and X = S, Se) van der Waals heterostructures. The
      stability of most favorable stacking is confirmed by calculating the binding
      energy and phonon spectrum. SiC-MoS2 is found to be a direct band gap type-II
      semiconducting heterostructure. Moderate in-plane tensile strain is used to
      achieve a direct band gap with type-II alignment in the SiC-WS2, SiC-MoSe2 and
      SiC-WSe2 heterostructures. A difference in the ionization potential of the
      corresponding monolayers and interlayer charge transfer further confirmed the
      type-II band alignment in these heterostructures. Furthermore, the optical
      behaviour is investigated by calculation of the absorption spectra in terms of
      epsilon2(omega) of the heterostructures and the corresponding monolayers. The
      photocatalytic response shows that the SiC-Mo(W)S2 heterostructures can oxidize
      H2O to O2. An enhanced photocatalytic performance with respect to the parent
      monolayers makes the SiC-Mo(W)Se2 heterostructures promising candidates for water
      splitting.

PMID- 30207336
TI  - The H2 sensing properties of facets-dependent Pd nanoparticles-supported ZnO
      nanorods.
AB  - The loading of noble-metal nanoparticles (NPs) is an effective approach for the
      enhancement of H2 sensing performances, although there have been rare reports
      focused on the effect of the facets of noble-metal nanoparticles in the H2
      sensing performance. The catalytic and adsorption performance of noble-metal
      nanocrystals is mainly determined by their exposed facets, while the gas sensing
      performance of sensors is strongly correlated to the adsorption and reaction
      between the gases and sensor materials. Hence, it is very important to study the
      gas sensing performance of the different facets-exposed noble-metal
      nanoparticles. In this study, a set of shape-controlled Pd NPs have been prepared
      and loaded onto the ZnO nanorods, and the gas sensing performance of the Pd
      nanoparticle-loaded ZnO to 250 ppm of H2 has been detected. The results indicate
      that the cubic Pd NPs-loaded ZnO shows higher and faster sensing response to H2
      than the octahedral and spherical Pd-loaded ZnO owing to the stronger adsorption
      of the H2 by cubic Pd NPs enclosed by (100) facets than the octahedral NPs
      enclosed by (111) facets. The cubic Pd NPs-loaded ZnO also exhibits better
      sensing selectivity and repeatability towards H2.

PMID- 30207339
TI  - Synthesis of new allyl palladium complexes bearing purine-based NHC ligands with
      antiproliferative and proapoptotic activities on human ovarian cancer cell lines.
AB  - A series of new palladium allyl complexes bearing purine-based carbenes derived
      from caffeine, theophylline and theobromine have been prepared and characterized
      by NMR spectroscopy, and elemental analysis and in two cases by single crystal X
      ray diffraction. The cytotoxic and proapoptotic activities of compounds have been
      determined in vitro on human ovarian cancer A2780 and SKOV-3 cell lines. These
      experiments have shown that the palladium-allyl fragment induces a general
      cytotoxicity, but the choice of the supporting ligands is of paramount importance
      for achieving the best results. In particular complexes 4c, 4d and 5d exhibit a
      higher antiproliferative effect (IC50: 0.09, 0.81 and 0.85 MUM respectively) than
      cisplatin (IC50: 1.5 MUM) on A2780 cells, and 4d (IC50: 1.7 MUM vs. 5.94 MUM) on
      SKOV-3 cell line. Moreover in many cases it has been proved that the cytotoxicity
      of our complexes is associated with the induction of apoptosis.

PMID- 30207340
TI  - Correction: Surface induced smectic order in ionic liquids - an X-ray
      reflectivity study of [C22C1im]+[NTf2]<sup/>.
AB  - Correction for 'Surface induced smectic order in ionic liquids - an X-ray
      reflectivity study of [C22C1im]+[NTf2]-' by Julian Mars et al., Phys. Chem. Chem.
      Phys., 2017, 19, 26651-26661.

PMID- 30207344
TI  - Ambipolar remote graphene doping by low-energy electron beam irradiation.
AB  - We employ low-energy electron beam irradiation to induce both n- and p-doping in
      a graphene layer. Depending on the applied gate voltage during the irradiation,
      either n- or p-doping can be achieved, and by setting an appropriate irradiation
      protocol, any desired doping levels can be achieved.

PMID- 30207342
TI  - Synthesis, structure and magnetic investigations of dinuclear lanthanide
      complexes based on 2-ethoxycinnamate.
AB  - A series of dinuclear lanthanide complexes incorporating the 2-ethoxycinnamate
      ligand have been synthesized and characterized using elemental analyses, infra
      red spectroscopy, X-ray diffraction and magnetic measurements. Depending on the
      nature of the lanthanide ion, three different isostructural series of respective
      formulas, [Ln(L)3(DMSO)(H2O)]2 (Ln = Ce (1), Nd (2)), [Ln(L)3(DMSO)x(DMF)y(H2O)]2
      (Ln = Gd (3), Dy (5) and Er (6)) and [Tb(L)3(DMF)(H2O)]2 (4) have been obtained.
      Investigations of their magnetic properties reveal a genuine single-molecule
      magnet behaviour observed for the dysprosium based compound 5, while a field
      induced slow relaxation of the magnetization is found for compounds 1, 2 and 3.

PMID- 30207346
TI  - Mg-Al hydrotalcite-supported Pd catalyst for low-temperature CO oxidation: effect
      of Pdn+ species and surface hydroxyl groups.
AB  - Hydrotalcite-like compounds (HTlcs) are promising supports or catalyst precursors
      for heterogeneous catalysts. Herein, MgAl-HTlcs-supported Pd catalyst was
      fabricated, and two Pd catalysts supported on Mg(OH)2 and Al(OH)3 were prepared
      for comparison. The presence of hydroxyl groups (OH-) in the support is important
      for obtaining uniform Pd nanoparticles with small sizes. We found that Pdn+
      species are more active than Pd0 in low temperature CO oxidation due to their
      lower barrier in CO activation. The Pd/MgAl-HT catalyst shows the most stable
      Pdn+ at a temperature lower than 90  degrees C, leading to the highest catalytic
      activity towards CO oxidation. Pdn+ in the Pd/Al(OH)3 catalyst is more stable
      than that in Pd/Mg(OH)2 at low temperature, which is ascribed to its smaller
      temperature hysteresis (Thysteresis) between the oxidation and re-reduction
      cycles. The effect of hydroxyl groups on stabilizing Pd species is related to the
      stability of Pd catalyst in CO oxidation reaction.

PMID- 30207347
TI  - Highly efficient and stable semi-transparent perovskite solar modules with a
      trilayer anode electrode.
AB  - Highly efficient and stable semi-transparent CH3NH3PbI3 perovskite photovoltaic
      cells are realized by using an ITO/MoOx bilayer conductive oxide as the anode
      electrode with a cyclopenta[2,1-b;3,4-b']dithiophene (CT) based hole-transport
      material (HTM), which allows bifacial illumination from both sides of the
      electrodes. The wide bandgap MoOx thin film is not only to be an electron
      blocking layer, but also to be a passivation layer which can withstand the
      excessive energy bombardment during the magnetron sputtering process for the
      deposition of a high-quality ITO thin film. Atomic-force microscopy images,
      transmittance spectra and water-droplet contact angle images show that the
      interfacial contact between MoOx and hole transport layer (HTL) strongly
      influences the short-circuit current density (JSC) and fill factor (FF). The
      highest power conversion efficiency (PCE) values for the bifacial perovskite
      solar cells (0.16 cm2) and modules (11.7 cm2) are 16.38% and 14.96%,
      respectively. In addition, the PCE of the ITO/MoOx/CT-HTM based perovskite solar
      module decreases slowly toward a stable value (~11%) for more than 700 h under
      wet environment conditions (70 +/- 5 RH%).

PMID- 30207348
TI  - Flexible multi-wavelength photodetector based on porous silicon nanowires.
AB  - Porous silicon nanowires (PSi NWs) responding to red, green and blue lights
      simultaneously are reported in this study. NWs with a diameter of 120 nm were
      prepared from p-type Si wafer by metal-catalyst-assisted etching. The NWs
      produced in this manner had an outer porous region consisting of Si nanocrystals
      small enough to ensure the quantum confinement effect. Hydrazine treatment
      passivated the porous region by reduction of the surface oxides and the formation
      of Si-H bonds. The energy band structure of the porous region was a direct
      transition type, while the emission/absorption energies corresponded to red (1.94
      eV), green (2.24 and 2.44 eV) and blue (2.98 eV) light photons. A device
      structure prepared by suspending 10 PSi NWs between two Al electrodes by
      dielectrophoresis generated photocurrents upon exposure to red, green and blue
      lights. The rising and decay times were both 30 MUs and the ratio of photocurrent
      to dark current was 92.0, 59.8 and 24.4 for the blue, green and red lights,
      respectively. The device could be bent down to the bending radius of 5 mm without
      any significant deterioration of the photoresponse performances. Further, the
      device survived repeated bending and unbending over 10 000 cycles with this
      bending radius, demonstrating its application potential as a flexible device with
      multiple-wavelength photosensing capabilities.

PMID- 30207349
TI  - Evaluating the consumption of chemical products and articles as proxies for
      diffuse emissions to the environment.
AB  - In this study we have evaluated the use of consumption of manufactured products
      (chemical products and articles) in the EU as proxies for diffuse emissions of
      chemicals to the environment. The content of chemical products is relatively well
      known. However, the content of articles (products defined by their shape rather
      than their composition) is less known and currently has to be estimated from
      chemicals that are known to occur in a small set of materials, such as plastics,
      that are part of the articles. Using trade and production data from Eurostat in
      combination with product composition data from a database on chemical content in
      materials (the Commodity Guide), we were able to calculate trends in the apparent
      consumption and in-use stocks for 768 chemicals in the EU for the period 2003
      2016. The results showed that changes in the apparent consumption of these
      chemicals over time are smaller than in the consumption of corresponding products
      in which the chemicals are present. In general, our results suggest that little
      change in chemical consumption has occurred over the timespan studied, partly due
      to the financial crisis in 2008 which led to a sudden drop in the consumption,
      and partly due to the fact that each of the chemicals studied is present in a
      wide variety of products. Estimated in-use stocks of chemicals show an increasing
      trend over time, indicating that the mass of chemicals in articles in the EU,
      that could potentially be released to the environment, is increasing. The
      quantitative results from this study are associated with large uncertainties due
      to limitations of the available data. These limitations are highlighted in this
      study and further underline the current lack of transparency on chemicals in
      articles. Recommendations on how to address these limitations are also discussed.

PMID- 30207350
TI  - A non-innocent pincer H3LONS ligand and its corresponding octahedral low-spin
      Fe(iii) complex formation via ligand-centric homolytic S-S bond scission.
AB  - In the presence of FeCl3 and Et3N, a ligand H4Ldtda(AP) underwent S-S bond
      cleavage and generated a pincer non-innocent H3LONS ligand, which formed a
      homoleptic, six-coordinate, low-spin Fe(iii) complex (1). The complex comprised
      two 2-iminobenzosemiquinone (1-) pi-radicals and one thiyl pi-radical.

PMID- 30207351
TI  - Influence of extruded lentil containing high chromium nutritional yeast on the
      main physiological factors associated with metabolic syndrome in rodent models.
AB  - Insulin resistance, obesity and dyslipidemia are the main physiological factors
      associated with metabolic syndrome. The objectives of this study were to
      understand the effects of diets containing extruded lentil fortified with high
      chromium nutritional yeast (YCr) or chromium picolinate on glucose tolerance,
      clearance and fasting blood glucose concentrations in Normal and Obese (Ob/Ob)
      mice and to determine the effects of the diets on the mice plasma lipid profiles.
      Diets A, B and C contained YCr in different doses and concentrations, as follows:
      Diet A = 15.7 g and 16 ppm, B = 157.1 g and 16 ppm, and C = 299.3 g and 27 ppm,
      respectively. Diet D contained chromium picolinate at a dose and concentration of
      15.7 g and 16 ppm, respectively. Intraperitoneal glucose tolerance tests and
      intraperitoneal insulin tolerance tests were conducted at 4-weeks and 8-weeks
      post diet initiation, in addition to, plasma lipoprotein profiles and organ
      weights. Normal mice showed only slight variability with respect to the studied
      biological parameters compared to the Ob/Ob mice group. Results indicated that
      following 4-weeks of diet supplementation, Ob/Ob mice fed diets A, C and D had
      significantly (p < 0.05) lower fasting blood glucose (FBG) than Ob/Ob mice fed
      Diet B. However, after 8-weeks Ob/Ob mice fed Diet C, containing YCr, had a
      significantly (p < 0.05) lower FBG than mice supplemented with Diet D, containing
      chromium picolinate. Therefore, based on these findings, it was concluded that
      YCr at the highest concentration and dose was more effective than chromium
      picolinate. These results indicate that ready-to-eat snacks and breakfast cereal
      type products supplemented with chromium in the form of YCr could be used as
      vehicles for the amelioration of main physiological factors associated with
      metabolic syndrome.

PMID- 30207352
TI  - Regioselective B-H/C-H activation and metal-metal bond formation induced by half
      sandwich metals complexes at hydroxy-substituted o-carboranes.
AB  - A binuclear iridium complex, (Cp2*Ir2(CH2O)C2B10H8) (6), with a unique metal
      metal bond has been synthesized and fully characterized. Importantly, this
      complex is constructed via selective C-H and B(3)-H bond activation on the
      carborane precursor. Additionally, when the proligand (2-pyridine)(o
      carboranyl)methanol ligand was combined with a half-sandwich iridium complex,
      selective B(6)-H bond activation or metal-carbon bond formation can be induced by
      the use of different bases. And the rhodium complex constructed from (2
      pyridine)(o-carboranyl)methanol ligand containing a metal-carbon bond has been
      obtained and fully characterized.

PMID- 30207353
TI  - A novel mesoionic carbene based highly fluorescent Pd(ii) complex as an
      endoplasmic reticulum tracker in live cells.
AB  - A recent study advocates that endoplasmic reticulum (ER) dysfunction may be
      linked to critical neurotrauma and advanced tauopathy. In this regard, targeting
      the ER warrants urgent attention towards the therapeutic treatment of neurotrauma
      related neurodegeneration. Herein, we report the synthesis of a new N
      heterocyclic mesoionic carbene based highly fluorescent square-planar Pd(ii)
      complex 1, with a high quantum yield (0.737). Probe 1 is a non-toxic probe for
      selectively labeling the endoplasmic reticulum in live cells.

PMID- 30207354
TI  - Effect of an alkyl substituent and spacer length in benzene-centered tripodal
      diglycolamides on the sequestration of minor actinides.
AB  - Three benzene-centered tripodal diglycolamide (Bz-T-DGA) ligands, where
      diglycolamide (DGA) moieties are tethered to the central benzene ring through a
      methylene spacer and having either a hydrogen atom (LI) or an isopentyl group
      (LII) attached to the N-atom, and DGA moieties attached via an ethylene spacer
      and having an isopentyl group attached to the N-atom (LIII), were studied for
      their complexation and extraction abilities towards trivalent actinides and
      lanthanides. The distribution ratio of Am(iii) and Eu(iii) with 1 mmol L-1 ligand
      in 5% iso-decanol/n-dodecane followed the order: LII > LIII > LI. The
      substitution of the H atom with the isopentyl group on the N-atom of the DGA
      moieties resulted in two orders of magnitude enhancement in the extraction
      ability of the ligand. On the other hand, increase in the spacer length between
      the benzene ring and the DGA moieties resulted in several fold reduction in the
      extraction ability of the ligand. Spectroscopic studies with Eu3+ ions in
      acetonitrile also confirmed the metal/ligand complex formation constant in the
      order: LII > LIII > LI. Luminescence decay lifetimes of Eu3+/ligand complexes
      confirmed the absence of water molecules and that all the primary coordination
      sites of the metal ion are occupied by the ligands.

PMID- 30207356
TI  - Current advances in the catalytic conversion of carbon dioxide by molecular
      catalysts: an update.
AB  - Due to the high emissions of CO2 and the related environmental impact, the
      chemical transformation of CO2 to useful industrially relevant products or their
      precursor is of significant interest. Recycling CO2 as a building block for the
      synthesis of chemicals may not only reduce further emission by at least replacing
      oil-derived feedstocks, but also provide the advantages of CO2 as an inexpensive,
      non-toxic and easily available substrate. The catalytic conversion of CO2 into
      small, useful molecules such as carbonates, methyl amines, methanol, formic acid,
      etc. by molecular catalysts is an interesting topic that has strongly developed
      in recent years. This review provides an overview of current scientific progress
      in the activation and conversion of carbon dioxide with industrially and
      scientifically relevant substrates using molecular catalysts. Metal-based
      catalysts are presented in the first part of the review whereas metal-free
      systems are described in the second part.

PMID- 30207357
TI  - Two luminescent lanthanide(iii) metal-organic frameworks as chemosensors for high
      efficiency recognition of Cr(vi) anions in aqueous solution.
AB  - Two new lanthanide(iii) metal-organic frameworks (MOFs)
      {[(CH3)2NH2]2[Ln4(FDA)7(DMF)2].0.5DMF}n [Ln = Eu (1), and Tb (2)] based on furan
      2,5-dicarboxylic acid (H2FDA) have been successfully assembled and well
      characterized in detail. These MOFs are isostructural and demonstrate 12
      connected sqc15 topologies, which are rarely observed in MOF chemistry,
      especially in lanthanide(iii) MOFs. Moreover, these two MOFs could show a
      tolerance towards moisture and organic solvents and satisfactory chemical
      stabilities. More importantly, they exhibit sensitive and selective luminescence
      quenching response towards Cr2O72- and CrO42- anions in aqueous solution with the
      average quenching Ksv values of 1.25 * 104 L mol-1 (Cr2O72-) and 3.56 * 103 L mol
      1 (CrO42-) for 1 and 1.46 * 104 L mol-1 (Cr2O72-) and 4.35 * 103 L mol-1 (CrO42-)
      for 2 and the detection limits of 1.14 * 10-4 mol L-1 (Cr2O72-) and 1.12 * 10-4
      mol L-1 (CrO42-) for 1 and 7.42 * 10-5 mol L-1 (Cr2O72-) and 1.27 * 10-4 mol L-1
      (CrO42-) for 2. The high quenching Ksv values and low detection limits make them
      more feasible in sensing Cr(vi) anions in aqueous solution. The possible
      detection mechanism has been discussed in detail.

PMID- 30207358
TI  - The many faces and important roles of protein-protein interactions during non
      ribosomal peptide synthesis.
AB  - Covering: up to July 2018 Non-ribosomal peptide synthetase (NRPS) machineries are
      complex, multi-domain proteins that are responsible for the biosynthesis of many
      important, peptide-derived compounds. By decoupling peptide synthesis from the
      ribosome, NRPS assembly lines are able to access a significant pool of amino acid
      monomers for peptide synthesis. This is combined with a modular protein
      architecture that allows for great variation in stereochemistry, peptide length,
      cyclisation state and further modifications. The architecture of NRPS assembly
      lines relies upon a repetitive set of catalytic domains, which are organised into
      modules responsible for amino acid incorporation. Central to NRPS-mediated
      biosynthesis is the carrier protein (CP) domain, to which all intermediates
      following initial monomer activation are bound during peptide synthesis up until
      the final handover to the thioesterase domain that cleaves the mature peptide
      from the NRPS. This mechanism makes understanding the protein-protein
      interactions that occur between different NRPS domains during peptide
      biosynthesis of crucial importance to understanding overall NRPS function. This
      endeavour is also highly challenging due to the inherent flexibility and dynamics
      of NRPS systems. In this review, we present the current state of understanding of
      the protein-protein interactions that govern NRPS-mediated biosynthesis, with a
      focus on insights gained from structural studies relating to CP domain
      interactions within these impressive peptide assembly lines.

PMID- 30207359
TI  - SiO2 aerogel monolith allows ultralow amounts of TiO2 for the fast and efficient
      removal of gaseous pollutants.
AB  - Coupled adsorption and photocatalytic oxidation brings high expectations
      regarding the fast and efficient removal of gaseous pollutants in air. However,
      to fabricate an adsorbent-photocatalyst composite, coating of a photocatalyst on
      adsorbent support inevitably results in loss of adsorption and light blocking on
      interior surfaces. In this work, we attempt to develop an adsorbent-photocatalyst
      monolith composite, which not only perfectly retains original high adsorption
      capacity, but also allows complete penetration of UV light through the whole
      monolith. We employ a SiO2 aerogel monolith with a diameter of 2.5 cm and
      thickness of 0.7 cm as adsorbent and support. After atomic layer deposition (ALD)
      followed by calcination, 0.32-1.25 wt% TiO2 is dispersed on the skeleton of the
      SiO2 aerogel. In spite of such a low level of loading, the monolith composites
      exhibit fast and efficient removal of gaseous acetaldehyde and NO. Therein, the
      best performance is achieved at a loading of 0.6 wt% TiO2. By dark adsorption,
      the acetaldehyde pollutant with initial concentration of 200 ppm can be adsorbed
      by 54% within 10 min. Moreover, the light transmittance at 387 nm can be retained
      as high as 6% after penetrating through the whole monolith, confirming that all
      loaded TiO2 nanoparticles can participate in the photocatalytic oxidation of
      acetaldehyde. Under UV irradiation with intensity close to natural sunlight, the
      preadsorbed acetaldehyde can be completely mineralized into CO2 by photocatalytic
      oxidation in another 60 min, benefiting from the ultradispersion of TiO2
      nanoparticles inside the SiO2 aerogel. The study provides a novel three
      dimensional model of an adsorbent-photocatalyst composite for the fast and
      efficient removal of gaseous pollutants.

PMID- 30207360
TI  - Crystal structural design of exposed planes: express channels, high-rate
      capability cathodes for lithium-ion batteries.
AB  - Developing high-performance lithium ion batteries (LIBs) requires optimization of
      every battery component. Currently, the main problems lie in the mismatch of
      electrode capacities, especially the excessively low capacity of cathodes
      compared with that of anodes. Due to the anisotropy of the crystal structure,
      different crystal planes play different roles in the transmission of lithium
      ions. Among these, the {010} facets of layered-structure materials, the (110)
      planes of spinel cathodes and the (010) planes of olivine cathodes can provide
      open surface structures, which furnish express channels for the rapid and
      efficient transmission of lithium ions, leading to enhanced rate performance.
      However, due to the high-energy surfaces of these crystal planes, they tend to
      disappear in the synthetic process, forming thermodynamic equilibrium products
      dominated by low-energy and electrochemically-inactive planes. From the structure
      design of the material itself, preparing functional materials with specific
      morphologies and crystal structures is considered to be the most effective way to
      improve the cyclability and rate performance of LIB cathodes. In this review, we
      highlight the latest developments in selectively exposing the crystal planes of
      LIB cathode materials. The synthetic method, the corresponding electrochemical
      performance, especially the rate capability, and the growth mechanism have been
      systematically summarized for layered-structure cathodes of LiCoO2, LiNixCoyMn1-x
      yO2 and Li2MnO3.LiMO2, spinel cathodes of LiMn2O4 and LiNi0.5Mn1.5O4, and olivine
      cathodes of LiFePO4. This in-depth discussion and understanding is beneficial for
      the rational design of well-performing LIB cathodes and can provide direction and
      perspectives for future work.

PMID- 30207361
TI  - Lipid profiling in serum from apolipoprotein E-knock out mice fed with different
      diets and its application to the study of the regulatory effect on lipid
      metabolism.
AB  - Atherosclerosis is a chronic disease associated with oxidative stress and
      inflammatory activation and is the main underlying trigger for cardiovascular
      disease. There are many cardiovascular health products in the market; in order to
      evaluate the effect of these products, in this paper, a novel lipid profiling
      platform was established using the shot-gun mass spectrum method for the analysis
      of free fatty acid and phospholipids, and the high performance liquid
      chromatography coupled with mass spectroscopy method for the analysis of lipid
      mediators and triacylglycerol, respectively, in serum from male apolipoprotein E
      knock out mice after different diet interventions. Changes in the four lipids
      above, and pathways and regulation of lipid metabolism in mice from different
      groups were further investigated. The result showed that all cardiovascular
      health products showed some certain potential to alleviate atherogenesis and
      ameliorate inflammation; among them, lemon apple cider vinegar drink and seal oil
      could significantly decrease triacylglycerol in mouse serum. The establishment of
      this lipidome profiling platform helps to better understand the metabolism
      regulation and intervention mechanism of different cardiovascular health products
      in chronic diseases, such as atherogenesis. This platform could be applied to
      other cardiovascular health products and provide reliable lipid profiling data
      for their potential effect.

PMID- 30207362
TI  - Ginsenoside Rg5 induces apoptosis and autophagy via the inhibition of the
      PI3K/Akt pathway against breast cancer in a mouse model.
AB  - Breast cancer is the most frequently diagnosed cancer and has become the main
      cause of cancer-related death among women worldwide. Traditional chemotherapy for
      breast cancer has serious side effects for patients, such as the first-line drug
      docetaxel. Ginsenoside Rg5, a rare ginsenoside and the main ingredient extracted
      from fine black ginseng, has been proved to have anti-breast cancer efficacy in
      vitro. Here, the in vivo anti-breast cancer efficacy, side effects and potential
      molecular mechanisms of Rg5 were investigated on a BALB/c nude mouse model of
      human breast cancer. The tumor growth inhibition rate of high dose Rg5 (20 mg kg
      1) was 71.4 +/- 9.4%, similar to that of the positive control docetaxel (72.0 +/-
      9.1%). Compared to docetaxel, Rg5 showed fewer side effects in the treatment of
      breast cancer. Treatment with Rg5 induced apoptosis and autophagy in breast
      cancer tissues. Rg5 was proved to induce caspase-dependent apoptosis via the
      activation of the extrinsic death receptor and intrinsic mitochondrial signaling
      pathways. The autophagy induction was related to the formation of an
      autophagosome and accumulation of LC3BII, P62 and critical Atg proteins. Further
      studies showed that Rg5 in a dose-dependent manner induced apoptosis and
      autophagy through the inhibition of the PI3K/Akt signaling pathway as indicated
      by the reduced phosphorylation level of PI3K and Akt. Taken together, Rg5 could
      be a novel and promising clinical antitumor drug targeting breast cancer.

PMID- 30207363
TI  - Amino-nitramino functionalized triazolotriazines: a good balance between high
      energy and low sensitivity.
AB  - Using a simple and efficient approach, a series of fused triazolo-triazine
      compounds, namely, 2,5-dinitramide-7-amino-[1,2,4]triazolo[1,5-a][1,3,5]triazine
      (2) and its energetic salts (4-9, 11-13), were prepared by nitration of 2,5,7
      triamine [1,2,4]triazolo[1,5-a][1,3,5]triazine (1) with 100% nitric acid,
      followed by reacting with the corresponding bases. All new compounds were
      comprehensively characterized. Structures of 2 and 4 were further confirmed by
      single crystal X-ray diffraction. Based on the measured densities and calculated
      heats of formation (Gaussian 09), detonation pressures and velocities were
      evaluated by EXPLO5, falling in the range of 21.5-34.2 GPa and 7823-9313 m s-1,
      respectively. Notably, impact and friction tests show that these compounds are
      very insensitive (IS > 40 J; FS > 360 N). Moreover, two representative compounds
      5 and 6 with high decomposition temperature (5: 194  degrees C; 6: 199  degrees
      C), excellent detonation properties (vD = 9313, 9088 m s-1; P = 33.9, 34.1 GPa)
      as well as rarely low sensitivities (IS > 40 J; FS > 360 N) are promising
      candidates as high-energy and insensitive explosives.

PMID- 30207364
TI  - Liensinine perchlorate inhibits colorectal cancer tumorigenesis by inducing
      mitochondrial dysfunction and apoptosis.
AB  - SCOPE: Colorectal cancer (CRC) is one of the most common cancers worldwide with
      poor survival and limited therapeutic options, and there is an urgent need to
      develop novel therapeutic agents with good treatment efficiency and low toxicity.
      This study aims to examine the anticancer bioactivity of liensinine, a
      constituent of Nelumbo nucifera Gaertn, in CRC and investigate the action
      mechanisms involved. METHODS AND RESULTS: Liensinine was found to induce
      apoptosis and exert a significant inhibitory effect on the proliferation and
      colony-forming ability of CRC cells in a dose-dependent manner without any
      observed cytotoxicity on normal colorectal epithelial cells. Mechanistically, our
      data from quantitative proteomics, western blot analysis and flow cytometry
      analyses demonstrated that exposure of CRC cells to liensinine caused cell cycle
      arrest, mitochondrial dysfunction and apoptosis, accompanied by the activation of
      the JNK signaling pathway. Furthermore, animal experiments showed that liensinine
      markedly suppressed the growth of CRC tumor xenografts in nude mice by reducing
      the Ki-67 proliferation index, but did not damage the vital organs of the
      animals. CONCLUSION: This study demonstrated for the first time that liensinine,
      a food-source natural product, could be a novel therapeutic strategy for treating
      CRC without obvious side effects.

PMID- 30207365
TI  - Diffusion-reaction kinetics of microfluidic amperometric biosensors.
AB  - Amperometric biosensors are widely applied for rapid biomarker detection in
      physiological and environmental samples. The dynamics and linearity of the
      current signal, however, are only partially understood. This study investigates
      the diffusion-reaction kinetics of amperometric biosensing using a self-assembled
      monolayer (SAM) based biosensor for bacterial 16S rRNA. A numerical model is
      developed to optimize the chamber dimensions and elucidate the concentration
      dependences of the biosensor. The results revealed that depletion of substrates
      associated with the chamber dimension can limit the current signal in a target
      concentration dependent manner. This study provides practical guidelines in the
      design and interpretation of microfluidic amperometric biosensors for biochemical
      applications.

PMID- 30207366
TI  - Tin(ii) oxide carbodiimide and its relationship to SnO.
AB  - The compound Sn2O(CN2) was obtained as a brick-red crystalline powder from a
      solid-state reaction of equimolar amounts of SnCl2, SnO and Li2(CN2). Thermal
      analysis of the reaction indicates the formation of two intermediate compounds
      until Sn2O(CN2) is formed at 400  degrees C. The crystal structure of Sn2O(CN2)
      was determined in the space group Pccn (a = 13.3949(7) A, b = 5.2954(3) A, c =
      5.5369(2) A, Z = 4) from single-crystal X-ray diffraction data. The structure
      contains a Sn2+ ion with a 5s2 lone pair, situated in a fourfold, mixed O-/N
      coordination environment. The crystal structure of Sn2O(CN2) is analyzed and
      discussed in relation to that of SnO, namely by electronic-structure calculations
      and a COHP bonding analysis of Sn2O(CN2).

PMID- 30207367
TI  - Protonation and water exchange kinetics in sandwich polyoxometalates.
AB  - Density functional theory is used to explore the locus and consequences of
      protonation in [Zn4(HO)2(PW9O34)2]10-. The results are used to explain recent
      observations regarding the contrasting pH effects on the water-ligand exchange in
      [Mn4(H2O)2(P2W15O56)2]16- and [Co4(H2O)2(P2W15O56)2]16-, and the general effect
      of protonation on solvent exchange in metal oxides is discussed.

PMID- 30207369
TI  - Platinum-based metallomesogens bearing a Pt(4,6-dfppy)(acac) skeleton: synthesis,
      photophysical properties and polarised phosphorescence application.
AB  - Polarised phosphorescence has a bright future in backlighting for conventional
      liquid crystal displays due to its theoretical 100% internal quantum efficiency
      and low cost. However, there are scarce reports on polarised phosphorescence from
      metallomesogens. In this contribution, a platinum-based metallomesogen containing
      a mesogenic biphenyl (Pt1) was prepared and characterised. To further explore the
      effect of the substituent on mesophase and emission properties, a related complex
      Pt2 containing a tetraphenylethene (TPE) moiety was also synthesised. Both
      complexes melt at elevated temperatures but thereafter do not appear to
      crystallise on cooling. Complex Pt1 shows an enantiotropic nematic phase from
      which a broad emission can be seen when spread as a film; in solution, an
      intense, sky-blue emission is observed. For Pt2, which shows a monotropic SmA
      phase, the emission in the condensed phase is suppressed and there is only weak
      emission in solution. Polarisation-dependent photoluminescence with a polarised
      ratio of 5.4 was obtained for the aligned film of a Pt1:polyimide mixture. Using
      Pt1 as an emissive layer, non-doped, polarised organic light-emitting diodes
      presented a broad emission spectrum in the range of 450-900 nm with a polarised
      ratio of 1.33 and the highest external quantum efficiency of 1.1%. This research
      has an important significance for achieving broad-based polarised phosphorescence
      from platinum complex-based metallomesogens.

PMID- 30207370
TI  - Realizing uniform dispersion of MnO2 with the post-synthetic modification of
      metal-organic frameworks (MOFs) for advanced lithium ion battery anodes.
AB  - MnO2 nanoparticles were uniformly loaded on the surface of zeolitic imidazolate
      frameworks (ZIF-67 and ZIF-8) with ligand modification via a facile method with
      no other impurities introduced, with an average diameter of less than 10 nm. The
      MnO2/ZIF-COOH composites with stable structures can effectively alleviate
      expansion tension and provide a fast ion transport channel during electrochemical
      performance tests. The introduction of carboxyl (-COOH) increases the specific
      capacity due to Li insertion, enhances the conductivity with ionization, and
      improves stability through the formation of H-bonds. When used as an anode for
      lithium ion batteries, the MnO2/ZIF-67-COOH composite exhibits an excellent rate
      performance (1208 mA h g-1 at 50 mA g-1, 931 mA h g-1 at 100 mA g-1, 828 mA h g-1
      at 200 mA g-1, 684 mA h g-1 at 500 mA g-1, 566 mA h g-1 at 1000 mA g-1, 431 mA h
      g-1 at 2000 mA g-1, and 242 mA h g-1 at 5000 mA g-1) and high cycle stability
      even at high rates (a high capacity of 664 mA h g-1 is achieved at 1000 mA g-1
      and is maintained at approximately 100% after 100 cycles).

PMID- 30207371
TI  - The detailed acoustic signature of a micro-confined cavitation bubble.
AB  - Numerous scenarios exist for a cavitation bubble growing in a liquid. We focus
      here on cavitation phenomena within water under static tension in a confined
      environment. Drawing inspiration from the natural materials in plants, we design
      a novel experimental setup where a micrometric volume of water is confined by a
      hydrogel-based material. We show that, submerging the sample in a hypertonic
      solution, the water within the cavity is placed under tension and the acoustic
      emission produced by the resulting bubble nucleation is precisely detected. This
      new experimental procedure is able to strongly reduce the acoustic reflections
      occurring at the hydrogel/air interface with more classical techniques. We also
      propose a mathematical model to characterise the pressure wave emitted in order
      to correctly take into account the dissipation effect induced by the visco
      elastic behaviour of the confining hydrogel. Both bubble resonant frequency and
      damping are captured by the model and quantitatively match the values found in
      the experiments.

PMID- 30207373
TI  - Thiolation in arsenic metabolism: a chemical perspective.
AB  - In recent years, methylated thioarsenicals have been widely detected in various
      biological and environmental matrices, suggesting their broad involvement and
      biological importance in arsenic metabolism. However, very little is known about
      the formation mechanism of methylated thioarsenicals and the relation between
      arsenic methylation and thiolation processes. It is timely and necessary to
      summarize and synthesize the reported information on thiolated arsenicals for an
      improved understanding of arsenic thiolation. To this end, we examined the
      proposed formation pathways of methylated oxoarsenicals and thioarsenicals from a
      chemical perspective and proposed a novel arsenic metabolic scheme, in which
      arsenic thiolation is integrated with methylation (instead of being separated
      from methylation as currently reported). We suggest in the new scheme that
      protein-bound pentavalent arsenicals are critical intermediates that connect
      methylation and thiolation, with protein binding of pentavalent methylated
      thioarsenical being a key step for arsenic thiolation. This informative review on
      arsenic thiolation from the chemical perspective will be helpful to better
      understand the arsenic metabolism at the molecular level and the toxicological
      effects of arsenic species.

PMID- 30207374
TI  - Salvage of thrombosed arteriovenous fistulae of patients on hemodialysis: report
      on the experience of a Brazilian center.
AB  - INTRODUCTION: Hemodialysis vascular access thrombosis is an acute event that can
      interrupt the dialytic treatment. A timely management can restore access patency,
      avoiding the use of central venous catheters and their complications. OBJECTIVE:
      To present the experience from a Brazilian Interventional Nephrology Center (INC)
      in the salvage of arteriovenous fistula (AVF) and grafts for hemodialysis.
      METHODS: A retrospective study was performed to evaluate the primary and
      secondary patencies of 41 hemodialysis accesses with thrombosis confirmed by
      ultrasound and submitted to endovascular salvage procedures. We considered
      clinical success the use of the access for at least 3 subsequent hemodialysis
      sessions. The procedures were done in an outpatient center by interventional
      nephrologists. Patients were followed for up to 18 months with Doppler every 3
      months. RESULTS: Forty-five salvage procedures were performed in 41 accesses of
      40 hemodialysis patients with native AVF or grafts. Of these, 90% were AVF,
      mostly upper arm, and 10% were grafts. Clinical success rate was 60% (27
      procedures). Primary patency at 12 months was 39% and secondary was 52%. Gender
      of the patient, diabetes, and location of the access did not correlate
      statistically with outcomes. There were 3 major complications (anastomosis
      rupture, grade 3 hematoma, and anaphylactic shock). CONCLUSION: The majority of
      thrombosed accesses can be successfully treated, maintaining its long-term
      patency. The need of repeated intervention is frequent.

PMID- 30207375
TI  - Double immunofluorescence labeling for CD31 and CD105 as a marker for polyether
      polyurethane-induced angiogenesis in mice.
AB  - A crucial component of the integration between foreign implants and the host is
      angiogenesis. However, to date, none of the available techniques and/or
      endothelial markers employed to assess angiogenesis in the implant/host interface
      seems to be able to highlight vascular structures convincingly. In the present
      study we investigated and compared the expression of two endothelial cell
      markers: platelet endothelial cell adhesion molecule (PECAM-1) (CD31) and
      endoglin (CD105) using immunohistochemistry (IHC) and immunofluorescence (IF) to
      identify and quantify newly formed blood vessels in subcutaneous implants of
      polyether-polyurethane sponge of formalin-fixed paraffin-embedded tissue. At day
      14 post implantation the discs of the synthetic matrix were removed and processed
      for histological and morphometric analysis. In IHC staining for CD31 antibody the
      number of vessels was 2.27+/-0.69 and 5.25+/-0.46 for CD105. In IF for CD31 the
      number of vessels was 15.36+/-1.295 and 10.54+/-0.8213 for CD105. The level of
      cross-reaction was lesser in IF images compared with IHC images. Co-localization
      of CD31/CD105 using confocal images showed positive correlation (Pearson's co
      relation and Manders' equation). The double labeling for blood vessels using the
      IF technique for CD31/CD105 may be an important tool for evaluation of
      angiogenesis in biomaterial/host integration.

PMID- 30207376
TI  - Phospholipase D: A new mediator during high phosphate-induced vascular
      calcification associated with chronic kidney disease.
AB  - Vascular calcification (VC) is the pathological accumulation of calcium phosphate
      crystals in one of the layers of blood vessels, leading to loss of elasticity and
      causing severe calcification in vessels. Medial calcification is mostly seen in
      patients with chronic kidney disease (CKD) and diabetes. Identification of key
      enzymes and their actions during calcification will contribute to understand the
      onset of pathological calcification. Phospholipase D (PLD1, PLD2) is active at
      the earlier steps of mineralization in osteoblasts and chondrocytes. In this
      study, we aimed to determine their effects during high-phosphate treatment in
      mouse vascular smooth muscle cell line MOVAS, in the ex vivo model of the rat
      aorta, and in the in vivo model of adenine-induced CKD. We observed an early
      increase in PLD1 gene and protein expression along with the increase in the PLD
      activity in vascular muscle cell line, during calcification induced by ascorbic
      acid and beta-glycerophosphate. Inhibition of PLD1 by the selective inhibitor
      VU0155069, or the pan-PLD inhibitor, halopemide, prevented calcification. The
      mechanism of PLD activation is likely to be protein kinase C (PKC)-independent
      since bisindolylmaleimide X hydrochloride, a pan-PKC inhibitor, did not affect
      the PLD activity. In agreement, we found an increase in Pld1 gene expression and
      PLD activity in aortic explant cultures treated with high phosphate, whereas PLD
      inhibition by halopemide decreased calcification. Finally, an increase in both
      Pld1 and Pld2 expression occurred simultaneously with the appearance of VC in a
      rat model of CKD. Thus, PLD, especially PLD1, promotes VC in the context of CKD
      and could be an important target for preventing onset or progression of VC.

PMID- 30207377
TI  - Probing the interaction of a quercetin bioconjugate with Bcl-2 in living human
      cancer cells with in-cell NMR spectroscopy.
AB  - In-cell NMR spectroscopy has emerged as a powerful technique for monitoring
      biomolecular interactions at an atomic level inside intact cells. However,
      current methodologies are inadequate at charting intracellular interactions of
      nonlabeled proteins and require their prior isotopic labeling. Herein, we
      describe for the first time the monitoring of the quercetin-alanine bioconjugate
      interaction with the nonlabeled antiapoptotic protein Bcl-2 inside living human
      cancer cells. STD and Tr-NOESY in-cell NMR methodologies were successfully
      applied in the investigation of the binding, which was further validated in
      vitro. In-cell NMR proved a very promising strategy for the real-time probing of
      the interaction profile of potential drugs with their therapeutic targets in
      native cellular environments and could, thus, open a new avenue in drug
      discovery.

PMID- 30207378
TI  - A kinase-dead version of FERONIA receptor-like kinase has dose-dependent impacts
      on rosette morphology and RALF1-mediated stomatal movements.
AB  - The receptor-like kinase FERONIA (FER) pleiotropically affects plant
      reproduction, development, and stress tolerance. We recently showed that the FER
      ligand RALF1 promotes stomatal closure and inhibits stomatal opening in a G
      protein-dependent manner. FER responses have been designated as kinase-dependent
      or kinase-independent, based largely on fer complementation assays employing a
      kinase-dead FERK565R. Our quantification of FERK565R-GFP transcript and FERK565R
      GFP protein in fer complementation lines reveal that, even within individual
      complementation lines, different levels of FERK565R expression prevail. FERK565R
      GFP expression comparable to that of FER in Col-0 plants fail to elicit
      complementation of either fer rosette phenotypes or RALF1-elicited stomatal
      movements, whereas overexpression levels of FERK565R-GFP result in
      complementation. These results suggest possible alternative interpretations of
      previous conclusions regarding kinase-independent FER signaling.

PMID- 30207379
TI  - Effect of an equal-access military health system on racial disparities in
      colorectal cancer screening.
AB  - BACKGROUND: Racial disparities in colorectal cancer (CRC) screening are
      frequently attributed to variations in insurance status. The objective of this
      study was to ascertain whether universal insurance would lead to more equitable
      utilization of CRC screening for black patients in comparison with white
      patients. METHODS: Claims data from TRICARE (insurance coverage for active,
      reserve, and retired members of the US Armed Services and their dependents) for
      2007-2010 were queried for adults aged 50 years in 2007, and they were followed
      forward in time for 4 years (ages, 50-53 years) to identify their first lower
      endoscopy and/or fecal occult blood test (FOBT). Variations in CRC screening were
      compared with descriptive statistics and multivariate logistic regression.
      RESULTS: Among the 24,944 patients studied, 69.2% were white, 20.3% were black,
      4.9% were Asian, and 5.6% were other. Overall, 54.0% received any screening:
      83.7% received endoscopy, and 16.3% received FOBT alone. Compared with whites,
      black patients had higher screening rates (56.5%) and had 20% higher risk
      adjusted odds of being screened (95% confidence interval [CI], 1.11-1.29). Asian
      patients had a likelihood of screening similar to that of white patients (odds
      ratio [OR], 1.06; 95% CI, 0.92-1.23). Females (OR, 1.20; 95% CI, 1.10-1.33),
      active-duty personnel (OR, 1.15; 95% CI, 1.06-1.25), and officers (OR, 1.28; 95%
      CI, 1.18-1.37) were also more likely to be screened. CONCLUSION: Within an equal
      access, universal health care system, black patients had higher rates of CRC
      screening in comparison with prior reports and even in comparison with white
      patients within the population. These findings highlight the need to understand
      and develop meaningful approaches for promoting more equitable access to
      preventative care. Moreover, equal-access, universal health insurance for both
      the military and civilian populations can be presumed to improve access for
      underserved minorities.

PMID- 30207381
TI  - Partial nephrectomy for T1b and T2 renal masses: A subtle paradigm shift and a
      new synthesis.

PMID- 30207380
TI  - Partial nephrectomy is not associated with an overall survival advantage over
      radical nephrectomy in elderly patients with stage Ib-II renal masses: An
      analysis of the national cancer data base.
AB  - BACKGROUND: Partial nephrectomy (PN) is recommended for localized T1a (<=4 cm)
      renal masses and is preferred over radical nephrectomy (RN) for amenable T1b/T2
      (>4 cm) tumors. The objective of the current study was to assess overall survival
      (OS) differences between PN and RN in patients with T1 and T2 renal cell
      carcinoma (RCC). METHODS: The National Cancer Data Base was queried for patients
      with T1 and T2 RCC who underwent PN or RN from 2004 to 2014. Trends in surgery
      were evaluated using Cochran-Armitage tests. Differences in OS were assessed
      using adjusted Kaplan-Meier methods. The effects of procedure on OS were analyzed
      using propensity score-based, weighted Cox proportional hazards models. RESULTS:
      In total, 212,016 patients with T1 and T2 RCC who underwent either RN (59.7%) or
      PN (40.3%) were included. The use of PN rose from 2004 to 2014 (T1a: from 40.6%
      to 71.4%; T1b/T2: from 8.4% to 26.5%; P < .01). Adjusted 5-year OS was longer for
      patients who underwent PN in both subsets, although effect magnitude was reduced
      in the T1b/T2 cohort (T1a: 89.6% vs 85.1%; hazard ratio [HR], 0.73; 95%
      confidence interval [CI], 0.70-0.75; P < .01; T1b/T2: 82.5% vs 80.8%; HR, 0.88;
      95% CI, 0.83-0.94; P = .01). The benefit of PN on OS diminished as age and time
      from diagnosis increased; no OS improvement was observed in patients age >=75
      years who had T1b/T2 tumors (HR, 0.89; 95% CI, 0.76-1.06). CONCLUSIONS: Receipt
      of PN is associated with improved OS in patients with T1a RCC. No procedure
      related differences in OS were observed for patients age >=75 years who had
      tumors measuring >4 cm. Decisions to undergo PN for T1b/T2 tumors should be based
      on individualized risk assessment.

PMID- 30207382
TI  - The Effects of Multiple Dimensions of Risk and Protective Factors on Depressive
      Symptoms Among Nonresident African American Fathers.
AB  - Compared to other groups, African American men experience proportionately greater
      adverse social and economic circumstances, which have been linked to poor mental
      health. A growing body of literature has begun to examine depressive symptoms
      among African American men; however, limited literature has examined the
      concurrent contributions of risk and protective factors among nonresident African
      American fathers. This study examined the relative contribution of perceived
      financial strain, perceived neighborhood characteristics, and interpersonal
      stress on depressive symptoms among 347 nonresident African American fathers.
      Social support was examined as a protective factor for depressive symptoms.
      Results from hierarchical regression analyses indicated interpersonal stress was
      associated with depressive symptoms even after controlling for perceived
      financial strain, perceived neighborhood characteristics, and specific
      sociodemographic factors. Additionally, among fathers with high interpersonal
      stress, having more social support buffered the negative effect of interpersonal
      stress on depressive symptoms. Findings suggest experiencing strain from multiple
      dimensions can increase the risk of depressive symptoms among nonresident African
      American fathers. We also found that interpersonal stress was especially harmful
      for mental health. Family service providers and mental health professionals
      should incorporate stress management techniques to reduce stressful interpersonal
      relationships as a way to lower depressive symptoms among nonresident African
      American fathers.

PMID- 30207383
TI  - Multiple roles for O-glycans in Notch signalling.
AB  - Notch signalling regulates a plethora of developmental processes and is also
      essential for the maintenance of tissue homeostasis in adults. Therefore, fine
      tuning of Notch signalling strength needs to be tightly regulated. Of key
      importance for the regulation of Notch signalling are O-fucose, O-GlcNAc and O
      glucose glycans attached to the extracellular domain of Notch receptors. The EGF
      repeats of the Notch receptor extracellular domain harbour consensus sites for
      addition of the different types of O-glycan to Ser or Thr, which takes place in
      the endoplasmic reticulum. Studies from Drosophila to mammals have demonstrated
      the multifaceted roles of O-glycosylation in regulating Notch signalling. O
      glycosylation modulates different aspects of Notch signalling including
      recognition by Notch ligands, the strength of ligand binding, Notch receptor
      trafficking, stability and activation at the cell surface. Defects in O
      glycosylation of Notch receptors give rise to pathologies in humans. This Review
      summarizes the nature of the O-glycans on Notch receptors and their differential
      effects on Notch signalling.

PMID- 30207384
TI  - American Headache Society Survey About Urgent and Emergency Management of
      Headache Patients.
AB  - BACKGROUND: Emergency department (ED) visits for migraine are burdensome to
      patients and to the larger healthcare system and society. Thus, it is important
      to determine strategies used to prevent ED visits and the common communication
      patterns between headache specialists and the ED team. OBJECTIVE: We sought to
      understand: (1) Whether headache specialists use headache management protocols.
      (2) The strategies they use to try and reduce the number of ED visits for
      headache. (3) Whether protocols are used in the EDs with which they are
      affiliated. (4) The level of satisfaction with the coordination of care between
      headache physicians and the ED. METHODS: We surveyed via SurveyMonkey members of
      the American Headache Society Emergency Department/Refractory/Inpatient (EDRI)
      Section to understand their practice regarding patients who call their office to
      be seen urgently, and to understand their communication with their local EDs.
      RESULTS: There were 96 eligible AHS members, 50 of whom responded to
      questionnaires either by email or in person (52%). Of these, 59% of respondents
      reported giving rescue treatment to their patients to manage acute attacks. Fifty
      four percent reported using standard protocols for outpatients not responding to
      usual acute treatments. In the event of a request for urgent care, 12% of
      specialists reported bringing patients into the office most or all of the time,
      and 20% reported sending patients to the ED some or most of the time for headache
      management. Thirty-six percent reported prescribing a new medicine and 30%
      reported providing telephone counseling some/most/all of the time. Sixty percent
      reported that their ED has a protocol for migraine management. Overall, 38% were
      usually or very satisfied with the headache care in the ED. CONCLUSIONS: A
      substantial number of headache specialists are dissatisfied with the care their
      patients receive in the ED. More standardized protocols for ED visits by patients
      with known headache disorders, and clear guidelines for communication between ED
      providers and treating physicians, along with better methods for follow-up
      following discharge from the ED, might appear to improve this issue.

PMID- 30207385
TI  - Effect of natural antioxidants on the physicochemical properties and stability of
      freeze-dried microencapsulated chia seed oil.
AB  - BACKGROUND: Chia oil possesses a very high content of polyunsaturated fatty
      acids, mainly alpha-linolenic acid. This characteristic makes this oil possess
      beneficial properties to health but gives it a high susceptibility to the
      oxidation process. Microencapsulation and the addition of natural antioxidants
      are alternatives to protect chia oil against oxidative deterioration. The aim of
      this study was to investigate the physicochemical characteristics and the
      oxidative stability of chia seed oil microencapsulated with different natural
      antioxidants (Guardian Chelox, which is a commercial blend of extracts from
      chamomile and rosemary, and essential oils from Origanum vulgare, Origanum x
      majoricum, and Mentha spicata) by freeze-drying using sodium caseinate and
      lactose as wall materials. RESULTS: The main physicochemical properties of the
      microencapsulated chia oil were similar regardless of the presence of
      antioxidant. The moisture content was 38.1 +/- 4.0 g kg-1 ; the
      microencapsulation efficiency was higher than 85% in all cases. The freeze-drying
      microencapsulation significantly enhanced (P <= 0.05) the oxidative stability of
      the chia oil. The addition of natural antioxidants conferred chia oil additional
      protection against lipid oxidation, depending on the type and concentration (500
      or 1000 mg kg-1 of the emulsion previous to freeze-drying) of the antioxidant.
      Among them, Guardian Chelox (1000 mg kg-1 ), presented the highest induction time
      obtained by the Rancimat accelerated oxidative stability test and the lowest
      peroxide values after 90 days of storage (33% relative humidity, 25 +/- 2 
      degrees C). Overall, the microparticles with antioxidants presented a lower
      degree of yellowing during storage than the control system. CONCLUSION: The use
      of different natural antioxidants confers freeze-dried microencapsulated chia
      seed oil additional protection against lipid oxidation. This information is
      relevant for the application of this oil, which is a rich source of omega-3 fatty
      acids, in the food industry. (c) 2018 Society of Chemical Industry.

PMID- 30207386
TI  - Economic Evaluation of Nutrition Support in the Prevention and Treatment of
      Pressure Ulcers in Acute and Chronic Care Settings: A Systematic Review.
AB  - BACKGROUND: Recent developments in nutrition intervention indicated clinical
      effectiveness for pressure ulcer (PU) prevention and treatment, but it is
      important to assess whether they are cost-effective. The aims of this systematic
      review are to determine the cost-effectiveness and clinical outcomes of nutrition
      support in PU prevention and treatment. METHODS: A systematic search of
      randomized controlled trials, observational studies, and statistical models that
      investigated cost-effectiveness and economic outcomes for prevention and/or
      treatment of PUs were performed using standard literature and electronic
      databases. RESULTS: Fourteen studies met the inclusion criteria, which included 3
      randomized controlled trials with their companion economic evaluations, 4 model
      based, 2 cohort, 1 pre and post, and 1 prospective controlled trial. Risk of bias
      assessment for all of the uncontrolled or observational trials revealed high or
      serious risk of bias. Interventions that incorporated specialized nursing care
      appeared to be more effective in prevention and treatment of PUs, compared with
      single intervention studies. There is a trend of improved PU healing when
      additional energy/protein are provided. PU prevention ($250-$9,800) was less
      expensive than treatment ($2,500-$16,000). Nutrition intervention for PU
      prevention was cost-effective in 87.0%-99.99% of the simulation models.
      CONCLUSIONS: There is potential cost-saving and/or cost-effectiveness of
      nutrition support in the long term, as predicted by the model-based PU prevention
      studies in the review. Prevention of PU also appears to be more cost-effective
      than treatment. A multidisciplinary approach to managing PU is more likely to be
      cost-effective.

PMID- 30207387
TI  - The effect of liraglutide on the proliferation, migration, and osteogenic
      differentiation of human periodontal ligament cells.
AB  - OBJECTIVE: Liraglutide (LIRA) is a novel antidiabetic therapy that may have anti
      inflammatory and bone protective effects. Thus, we studied the potential
      therapeutic effect of LIRA on periodontitis by assessing the effects of LIRA on
      the proliferation, migration, inflammation, and osteogenic differentiation of
      human periodontal ligament cells (hPDLCs) after LPS stimulation. MATERIAL AND
      METHODS: The expression of glucagon like-peptide 1 receptor (GLP-1R) was measured
      using qRT-PCR. HPDLCs proliferation after LIRA were analyzed using MTT assays.
      Cell migration was quantified using a wound-healing assay. The expression of
      inflammatory (IL-6 and TNF-alpha) was measured by qRT-PCR and ELISA in hPDLCs.
      The effect of LIRA on the mineralization potential of hPDLCs was assessed by
      alizarin red S staining. Furthermore, the expression of Runx2 and ALP was
      measured by qRT-PCR and Western blot in hPDLCs. RESULTS: GLP-1R mRNA was present
      on hPDLCs, and LIRA increased the expression of GLP-1R mRNA. When cultured with
      25, 50, 75, 100 and 125 nM LIRA for 24 h, hPDLCs proliferation was enhanced in a
      dose-dependent manner (P < 0.05), and 100 nM was optimal. LIRA promoted hPDLCs
      migration in a time-dependent manner. LPS significantly increased the expression
      of IL-6 and TNF-alpha (P < 0.01), decreased the formation of mineralization nodes
      (P < 0.01), and inhibited the expression of ALP and Runx2 (P < 0.05). LIRA
      treatment blocked the expression of IL-6 and TNF-alpha (P < 0.01), increased the
      formation of mineralization nodes (P < 0.01), and enhanced the expression of ALP
      and Runx2 (P < 0.05). CONCLUSION: LIRA can enhance the proliferation, migration,
      and osteogenic differentiation of hPDLCs and inhibit the inflammatory response.
      Thus, LIRA may have potential therapeutic use as an adjuvant treatment for human
      periodontitis, and this effect is independent of hypoglycemic activity.

PMID- 30207388
TI  - Periodontal condition and levels of bacteria associated with periodontitis in
      individuals with bipolar affective disorders: A case-control study.
AB  - OBJECTIVE: To evaluate the epidemiological and microbiological aspects of the
      potential association between bipolar affective disorder (BAPD) and
      periodontitis. METHODOLOGY: The present case-control study comprised 176
      individuals with BAPD and 176 controls. All individuals underwent a complete full
      mouth periodontal examination and microbiological sampling. Data on bleeding on
      probing, probing depth, and clinical attachment level in all present teeth were
      recorded. Quantification of total bacterial load and Aggregatibacter
      actinomycetemcomitans, Treponema denticola, and Porphyromonas gingivalis counts
      were performed through qPCR. Data were analyzed using univariate analysis,
      Spearman correlation and multivariate logistic regression. RESULTS: The
      prevalence of periodontitis was 39.7% among controls and 58.5% among individuals
      with BAPD (OR = 2.13; 95% CI 1.39-3.27). A. actinomycetemcomitans and P.
      gingivalis counts were significantly higher in individuals with BPAD and
      periodontitis. The final multivariate logistic regression revealed that
      periodontitis was strongly associated with the total bacterial load (OR = 1.91;
      95% IC = 1.0-1.99; P < 0.001) and the depressive phase of BPAD (OR = 28.94; 95%
      IC = 4.44-177.27; P < 0.001). CONCLUSION: BAPD was associated with increased risk
      for periodontitis. Individuals with BPAD presented higher levels of A.
      actinomycetemcomitans and P. gingivalis, suggesting that periodontitis could be a
      co-morbidity frequently found in individuals with BAPD.

PMID- 30207390
TI  - Closing Information Gaps in Kakuma Refugee Camp: A Youth Participatory Action
      Research Study.
AB  - This study explores the role of academic and social support on young people's
      educational pursuits in Kenya's Kakuma Refugee Camp. Pairing ethnographic methods
      with youth participatory action research, we find that support often manifests as
      abstract, decontextualized encouragement with little grounding in the educational
      opportunity structure. We argue that this motivational discourse generates
      information gaps, fueling aspirations that neither prepare youth for
      understanding, nor navigating the constraints they will encounter. In response,
      we designed a social media platform orienting Kakuma youth to the opportunity
      structure, while encouraging them to set realistic goals and plan accordingly.
      Designing a resource by, for, and with Kakuma youth, we illustrate that refugees
      have the rights and means to access information on which their everyday well
      being and futures depend. This study illustrates that critical understanding of
      local and global opportunities can empower, rather than demoralize, young people
      as they shape their futures in exile.

PMID- 30207389
TI  - Urine biochemistry to predict long-term outcomes in fetuses with posterior
      urethral valves.
AB  - OBJECTIVE: Because the literature on the predictive value of fetal urinalysis is
      controversial in fetuses with lower urinary tract obstruction, we determined the
      best model of fetal urine biochemical markers correlated with long-term postnatal
      renal function based on glomerular filtration rate (GFR). METHOD: This
      retrospective study concerned 89 fetuses with lower urinary tract obstruction and
      their renal function after 10 years of age. We correlated fetal urine biochemical
      markers (total protein, beta2-microglobulin, sodium, chloride, glucose, calcium,
      and phosphorus) with GFR at 10 to 30 years of age in 89 patients with posterior
      urethral valves. We defined five stages of chronic kidney disease (CKD). RESULTS:
      Of the 89 patients, 18 (20%) are 20 years old or over. Postnatal renal function
      was good in 67.4% (GFR > 60 mL/min/1.73 m2 ) and poor in 17% (GFR < 30
      mL/min/1.73 m2 ). All fetal urine markers differed between CKD stage 1 + 2 and
      CKD stage 4 + 5 (P < 0.001). beta2-microblobulin showed an 87% sensitivity for a
      72% specificity. A combination of beta2-microglobulin and chloride gave the best
      results (93% sensitivity and 71% specificity) versus amniotic fluid volume (80%
      sensitivity and 73% specificity). CONCLUSION: Fetal urine biochemistry predicts
      long-term (10-30 years) postnatal renal function.

PMID- 30207391
TI  - Intact and Damaged Wheat Starch and Amylase Functionality During Multilayered
      Fermented Pastry Making.
AB  - : The roles of native and damaged starch (DS) during fermented pastry making were
      examined by increasing the level of DS in wheat flour by ball-milling and/or by
      including amylase in the recipe. Increased DS levels increase laminated dough
      strength presumably by making less water available for the gluten. This effect
      was partly overcome by amylase use. During baking, a reduced resistance of the
      dough to gas cell expansion, as a result of enzymatic starch hydrolysis, seems
      responsible for increased pastry lift and improved crumb structure.
      Gelatinization of intact starch limits dough lift and expansion. Even at high
      amylase dosages structural collapse was limited, which suggests a significant
      role for gluten in pastry product structure formation. Differential scanning
      calorimetry and low-resolution 1 H nuclear magnetic resonance experiments
      indicated that increased levels of starch damage and amylase use impact the
      amylose network in the product and respectively increase and decrease the extent
      to which amylopectin retrogrades during storage. PRACTICAL APPLICATION: This
      research article evaluates the role of intact and damaged wheat starch during the
      production of fermented pastry products. An expanded knowledge on starch
      functionality during the different pastry production steps allows for a targeted
      selection of additives to improve product quality and production efficiency. The
      results obtained in this study can contribute to the realization of industrially
      feasible solutions for the production of quality pastry products.

PMID- 30207392
TI  - Adolescent self-harm with and without suicidality: cross-sectional and
      longitudinal analyses of a Swedish regional register.
AB  - BACKGROUND: Self-harm is common and there is a need for studies that investigate
      the relevance of this behavior in clinical samples to inform risk assessment and
      treatment. The objectives in the current studies were to compare clinical and
      psychosocial correlates and subsequent adverse outcomes in youth who present to
      child and adolescent mental health services (CAMHS) with self-harm only (SH),
      self-harm with suicidality (SH+SU), with those without any indication of SH or
      SH+SU. METHODS: We conducted a case-control study and a longitudinal cohort study
      using data from a regional clinical care register, and Swedish national
      registers. The case-control study included all patients (5-17 years) between 2011
      and 2015 (N = 25,161). SH and SH+SU cases were compared with controls (patients
      without SH) regarding a range of correlates. The longitudinal study included
      former CAMHS patients (N = 6,120) who were followed for a median time of 2.8
      years after termination of CAMHS contact regarding outcomes such as clinical care
      consumption, social welfare recipiency, and crime conviction. RESULTS: In the
      case-control study, both the SH and SH+SU groups received more clinical care, had
      lower global functioning, and higher odds of having mental disorders compared to
      controls. In most comparisons, the SH+SU group had more problems than the SH
      group. In the longitudinal study, the same pattern emerged for most outcomes; for
      example, the adjusted hazard ratio for recurrent care due to self-harm was 23.1
      (95% confidence interval [CI], 17.0-31.4) in the SH+SU group compared to 3.9 (95%
      CI, 2.3-6.7) in the SH group. CONCLUSIONS: Adolescent patients presenting with
      self-harm have higher risks for adverse outcomes than patients without self-harm.
      Suicidality in addition to self-harm is associated with more severe outcomes,
      importantly recurrent episodes of care for self-harm.

PMID- 30207393
TI  - Refractance window drying of fruits and vegetables: a review.
AB  - Fruit and vegetable drying to make leather, pestil or powder products is a
      challenging task. Traditional drying adversely affects the taste, colour,
      nutritional qualities and preservation of bioactive compounds due to high
      temperature exposure of the product. The substitute for traditional drying
      processes is consequently necessary to impart superior quality and preserve
      greater nutritional value in processed foods. Refractance window (RW) drying is a
      thin film drying system having high heat and mass transfer rates that speeds up
      the rate of drying. Polyester (Mylar), an infrared transparent plastic sheet
      transmits radiative heat to food during the RW drying process with higher drying
      rate, more retention of nutrients and low aroma and flavour loss. RW drying is
      reported to be affected by the thickness of puree or slices and temperature of
      drying, as thick samples need longer drying time, generate higher water activity,
      bring changes in colour parameters, experience higher effective diffusion
      coefficient (Deff ) and result in lower solubility of powder. RW drying was
      compared with different drying processes and was observed to have more retention
      of nutrients and be more economical. RW dried samples were better in terms of
      colour and textural quality when compared with other traditional drying methods.
      (c) 2018 Society of Chemical Industry.

PMID- 30207395
TI  - Developmental pathways of periodontal tissue regeneration: Developmental
      diversities of tooth morphogenesis do also map capacity of periodontal tissue
      regeneration?
AB  - Nothing is known on the impact of developmental divergence on periodontal tissue
      regeneration in vertebrate animals. Molecularly, the induction of tooth
      morphogenesis is highly conserved deploying across animal phyla a constant and
      reproducible set of gene pathways, which result in morphogenesis of multiple
      odontode forms and shapes. Genetic mutations positively affect animal speciation
      via evolving biting and masticatory forces as well as dietary habits selectively
      imprinted in animal phyla during evolutionary speciation. The geometry of the
      attachment apparatus of a tooth is important for the interpretation of the
      induction of cementogenesis with de novo Sharpey's fibres as in thecodonty, ie, a
      tripartite attachment of alveolar bone, periodontal ligament and cementum. This
      review addresses the tooth implantation in different animal clades from the
      fibrous attachment of the Elasmobranch Carcharinus obscurus dusky shark,
      reviewing the evolution and functional significance of cementum with functionally
      inserted Sharpey's fibres. In sharks there is a continuous tooth replacement
      mechanistically supported by the continuously erupting dental lamina. We show
      that the arching of the continuously erupting dental lamina, a critical step for
      the selachians' tooth differentiation, is prominently characterized by
      transforming growth factor-beta3 (TGF-beta3 ) expression not only within the
      dental lamina but also in cellular condensations in the mesenchymal tissues of
      the erupting tooth. Such findings indicate the pleiotropic multifaceted activity
      of a highly conserved mammalian gene across genera, masterminding tooth
      morphogenesis in both selachians and mammals as well as periodontal tissue
      induction in the non-human primate Papio ursinus. In P. ursinus, the induction of
      cementogenesis entails the expression of TGF-beta3 and osteocalcin with fine
      tuning and regulation of bone morphogenetic proteins BMP-2 and BMP-7, and
      upregulation of TGF-beta3 . TGF-beta3 autoinduction and upregulation during the
      induction of cementogenesis and osteogenesis in P. ursinus provide novel insights
      into the induction of cementogenesis. It is hypothesized that the evolutionary
      expression and upregulation of the TGF-beta3 gene may provide the mechanistic
      insights into the induction of extensive cementogenesis as seen in stem mammals
      and the induction of trabecular-like cementum formation in mosasaurs' tooth
      attachment. Aspidin, the precursor of cementum, was reported to appear 310-330
      million years ago (Ma) in Odontostraci armoured fish. Studies showed that the
      differentiation of cementum with inserted Sharpey's fibres is also present in
      lower amniotes such as Diatectomorpha or Diadectidae, the first herbivorous
      tetrapods, 323 Ma. In mosasaurs, 168-165 Ma, there is the induction of extensive
      trabeculation of cementum though nothing is known on the phylogenetic temporo
      spatial evolution of cementum before Diadectidae and stem mammals. The large
      trabeculations of cementum as seen in the attachment of extinct mosasaurs
      invocates a pleiotropic capacity of cemental growth previously unknown. The
      appearance of cementum facing a vascularized and innervated periodontal ligament
      space with Sharpey's fibres inserting on to mineralized cementum provides a
      multiform pleiotropic masticatory apparatus adapted to multiple biting and
      lacerating forces as well as finely tuned and controlled forces beyond
      mastication and deglutition. The remarkable cementogenesis as seen in stem
      mammals but particularly in mosasaurs with cemental trabeculations across the
      ligament space invocates the developmental capacity of cementum. The large
      cemental trabeculations as seen in mosasaurs and the cemental growth in stem
      mammals, together with regenerating scenarios in P. ursinus with large seams of
      cellular cementum and cementoid populated by contiguous cementoblasts indicate
      the continuous molecular cross-talk between cementum, newly formed cementoid
      matrix, cementoblasts and extracellular matrix soluble molecular signals. This
      molecular cross-talk may control the biomolecular homeostasis of both cementum
      and periodontal ligament, including angiogenesis. A further molecular scenario is
      invocated by the tight and exquisite anatomical relationships between the
      cementoid surfaces and the newly formed capillaries. The primitiveness of the
      craniate masticatory mineralized craniofacial apparatus has been controlled by
      several yet ancestral common genes not lastly the TGF-beta3 gene. The TGF-beta3
      might have been responsible for the induction of cementogenesis not only in
      extant P. ursinus but also in Diatectomorpha and mosasaurs, thus providing
      continuous evolutionary mechanisms for the induction of tissue morphogenesis
      across animal phyla for almost a billion years of evolution, epitomizing Nature's
      parsimony in controlling tissue induction and morphogenesis. TGF-beta receptor II
      regulates osterix expression via Smad-dependent pathways indicating that TGF-beta
      signalling acts as an upstream regulator of osterix during cementoblast
      differentiation. The presence of morphogenetic signals within the cemental matrix
      capable of inducing bone formation needs now to be assigned: bone induction
      initiated by extracted and partially purified cemental matrices may be the result
      of a slow release of embryonic remnants of osteogenic signals required and
      deployed during cementogenesis. The cementum may thus rule the periodontal
      ligament space homeostasis, remodelling and repair by releasing sequestered
      morphogenetic signals that were deployed during embryogenesis.

PMID- 30207394
TI  - Strontium enhances proliferation and osteogenic behavior of periodontal ligament
      cells in vitro.
AB  - BACKGROUND AND OBJECTIVE: Strontium (Sr) enhances osteogenic differentiation of
      certain multipotent cells. Periodontal ligament cells (PDLCs) are known to be
      multipotent, and Sr might be useful in periodontal bone tissue engineering. This
      study investigates the effect of high concentration of Sr on the proliferation
      and osteogenic behavior of PDLCs in vitro. MATERIAL AND METHODS: Primary human
      PDLCs were cultured in MEM + 10% FBS without (Ctrl) or with Sr in four diverse
      concentrations: Sr1, 11.3 * 10-3  mg/L, human serum physiological level; Sr2, 13
      mg/L, typical human serum level after strontium ranelate treatment; Sr3, 130
      mg/L, and Sr4, 360 mg/L. The spreading area (2, 4, 6, 24 hours), proliferation
      rate (1, 3, 7 days), osteogenic behavior (alkaline phosphatase - ALP activity, 7
      and 14 days; expression of osteogenic genes, ALP, Runt-related transcription
      factor 2 - RUNX2, osteopontin - OPN, osteocalcin - OCN, and osteoprotegerin -OPG,
      1, 3, 7, 14, 21 days), and formation of mineralized nodules (14 and 21 days) of
      the PDLCs were assessed. Data were compared group- and period-wise using ANOVA
      tests. RESULTS: Periodontal ligament cells cultured with Sr4 showed increased
      spreading area (after 4 hours), proliferation rate (from 3 days), and OCN and OPN
      (from 7 days) gene expression as compared to Ctrl, Sr1, Sr2, and Sr3. Sr4 also
      led to lower ALP activity (from 7 days), ALP (from 3 days), and RUNX2 (at 7 and
      14 days) gene expression, together with more evident formation of mineralized
      nodules, compared to Ctrl, Sr1, Sr2, and Sr3. CONCLUSION: Periodontal ligament
      cells responded to Sr4 with increased cellular proliferation and osteogenic
      behavior in vitro.

PMID- 30207396
TI  - Nickel and arsenite-induced differential oxidative stress and antioxidant
      responses in two Anabaena species.
AB  - In recent years, release of chemical pollutants has increased due to
      anthropogenic activities. Heterocystous filamentous cyanobacteria constitute
      dominant paddy microflora and are excellent biofertilizers augmenting rice
      productivity. Cyanobacteria are frequently exposed to toxic metals, nickel and
      arsenic are one of the major toxicants present. We exposed two species of
      diazotrophic cyanobacteria Anabaena sp. PCC 7120 and Anabaena doliolum, to sub
      lethal concentrations (15.0 and 9.0 MUM) of Ni2+ and (17.0 and 11 mM) of arsenite
      (AsIII) and analyzed at different days of treatments (0, 1, 7, and 15 days) for
      oxidative damage and antioxidative biomarkers. Lipid peroxidation was enhanced
      (1.5- to 2.5-fold increase in MDA content), indicating damaging effects of Ni2+
      and As(III) on membrane. Although Ni2+ and As(III), both induced oxidative stress
      in both species, Anabaena PCC 7120 experienced less stress than A. doliolum. This
      could be explained by a higher activity of antioxidant enzymes catalase (CAT),
      ascorbate peroxidase (APX), glutathione reductase (GR) in Anabaena PCC 7120 (4.6
      , 2.0- and 1.4-fold [Ni2+ ] 3.2-, 2.5-, and 2.08-fold [As]) compared to A.
      doliolum (4.2-, 2.5-, and 1.3-fold [Ni2+ ] and 3.2-, 3.33-, and 1.8-fold [As]).
      Moreover, superoxide dismutase registered less inhibition in Anabaena sp. PCC
      7120 (1.5 and 1.8) compared to A. doliolum (1.8 and 2.3) under Ni2+ and As(III)
      stress. In addition to, IBR revealed that As(III) imposes severe impact on both
      strain, however, A. doliolum suffers most. Therefore, the study demonstrates
      interspecies variation in survival strategy of two Anabaena species and
      difference in potential of two different toxicants to produce oxidative stress.

PMID- 30207397
TI  - Electrochemical Alkynyl/Alkenyl Migration for the Radical Difunctionalization of
      Alkenes.
AB  - An efficient electrochemical 1,2-sulfonylation/alkynylation of alkenes via
      radical 1,4-alkynyl migration of alkynyl-substituted tertiary alcohols is
      described, which used sodium sulfinates as sulfonyl sources affording the
      corresponding alpha-sulfonyl-beta-alkynylated products in moderate to excellent
      yields. This electrochemical reaction proceeds smoothly without the use of any
      metal catalyst, additive and oxidant and thus represents a new and eco-friendly
      strategy for the difunctionalization of unactive olefins, and also the first
      example of the electrochemical distal radical migration reaction.

PMID- 30207398
TI  - Oral features of Griscelli syndrome type II: A rare case report.
AB  - Griscelli syndrome (GS) is an autosomal-recessive disorder of the vesicle
      transport and membrane trafficking system first identified by Griscelli et al in
      1978. The three types of GS have specific genetic defects and systemic
      manifestations apart from classic partial pigmentary dilution, resulting in
      hypopigmentation of skin and silvery hair. GS-II occurs due to a defect in the
      Rab27a gene and is characterized by primary immune deficiency along with
      accelerated phases of a hemophagocytic lymphohistiocytosis (HLH) crisis. This
      rare disorder has been widely studied for dermatological, hematological, and
      neurological manifestations; however, the oral features and presentations have
      not been elucidated in detail. This report presents a case of a 4-year-old male
      with known mutation c.550C > T or p.R184X mutation (ENST00000396307) in Rab27a
      with oral features.

PMID- 30207399
TI  - Oral manifestations of Langerhans cell histiocytosis: A case series.
AB  - AIM: Langerhans cell histiocytosis (LCH) is an unusual proliferative disorder of
      bone marrow-derived histiocytes (Langerhans cells) that can produce focal or
      systemic manifestations. Oral manifestations of LCH can present as single or
      multiple lesions and can be a challenge in clinical practice. The aim of this
      paper is to present the clinicopathological features of a series of nine patients
      with oral involvement. METHODS AND RESULTS: The patient's age ranged from 2 to 63
      years being five males and four females. The most common oral site involvement
      was the hard-palate mucosa. Ulceration was the main clinical feature. Only two
      patients showed clearly jawbone involvement. In eight out of nine patients, the
      diagnosis of LCH was established because of the oral manifestations. CONCLUSION:
      The recognition of the clinical features of LCH oral manifestation is important
      to avoid misdiagnosis and to the establishment of the correct treatment. Thus,
      dentists can play a vital role in the diagnosis of LCH since oral lesions may be
      the earliest manifestation and sometimes the only sign of the disease.
      Furthermore, oral lesions may be the early signs of disease reactivation or a
      multisystem disease indication.

PMID- 30207400
TI  - Unexpected sequel to silver fluoride followed by stannous fluoride treatment of
      root stumps supporting an overlay denture in an aged-care patient.
AB  - An institutionalized high care dementia patient, who is unable to maintain his
      own oral health, presented with five lower anterior carious root stumps
      supporting a lower overlay denture. Due to limited cooperation, his root stumps
      were treated with only silver fluoride followed by stannous fluoride applied
      topically on a 4-monthly cycle. Almost one and a half years after his initial
      application, there were unexpected calculus formations on the root stumps
      accompanied by marked gingival inflammation and gingival hyperplasia. At this
      point prognosis was considered very poor. Because the patient's cooperation was
      so poor, no attempt was made to remove the calculus deposits. Following continued
      topical applications directly to the area, there was evidence of a marked and
      unexpected improvement in gingival health. Some 4 years and 4 months after the
      initial application, the root stumps demonstrated a hard glossy surface
      surrounded by healthy gingival tissue. There had been no change in the patient's
      oral care, minor changes to medications and there had been no operative or
      periodontal interventions.

PMID- 30207401
TI  - Approach to the Investigation of Nucleosome Structure by Using the Highly
      Emissive Nucleobase th dG-tC FRET Pair.
AB  - A distance- and orientation-factor-dependent FRET system is a useful and
      attractive approach to the investigation of the conformational dynamics of
      nucleosomes. In this study, the application of the highly emissive nucleobase th
      dG-tC FRET pair to 601 nucleosomes is reported. It was found that the th dG-tC
      FRET pair was successfully incorporated to 145 bp 601 sequences, and different
      FRET efficiencies were obtained for the designated donor and acceptor positions
      in the nucleosome.

PMID- 30207402
TI  - The human body is the magazine of inventions.

PMID- 30207403
TI  - Discovery of Small Molecule WWP2 Ubiquitin Ligase Inhibitors.
AB  - We have screened small molecule libraries specifically for inhibitors that target
      WWP2, an E3 ubiquitin ligase associated with tumour outgrowth and spread.
      Selected hits demonstrated dose-dependent WWP2 inhibition, low micromolar IC50
      values, and inhibition of PTEN substrate-specific ubiquitination. Binding to WWP2
      was confirmed by ligand-based NMR spectroscopy. Furthermore, we used a
      combination of STD NMR, the recently developed DEEP-STD NMR approach, and docking
      calculations, to propose for the first time an NMR-validated 3D molecular model
      of a WWP2-inhibitor complex. These first generation WWP2 inhibitors provide a
      molecular framework for informing organic synthetic approaches to improve
      activity and selectivity.

PMID- 30207404
TI  - Patient- and Nutrition-Derived Outcome Risk Assessment Score as a Predictor of
      Mortality in Critically Ill Surgical Patients: A Retrospective, Single-Center
      Observational Study.
AB  - BACKGROUND: The Patient- And Nutrition-Derived Outcome Risk Assessment (PANDORA)
      was recently validated for predicting mortality in hospitalized patients;
      however, its utility in the intensive care unit (ICU) remains unknown. METHODS:
      We investigated whether PANDORA is associated with 30, 90, and 180 day mortality
      in critically ill surgical patients by performing logistic regressions,
      controlling for age, sex, race, body mass index, macronutrient deficit, and
      length of stay. The area under the receiver operating characteristic curves (AUC)
      of PANDORA vs Acute Physiology and Chronic Health Evaluation (APACHE) II scores
      for mortality at each time point were also compared. RESULTS: 312 patients
      comprised the analytic cohort. PANDORA was associated with mortality at 30 (OR
      1.08; 95% CI 1.04-1.13; P < .001), 90 (OR 1.09; 95% CI 1.03-1.12; P < .001), and
      180 days (OR 1.10; 95% CI 1.06-1.15; P < .001). PANDORA and APACHE II were
      comparable for mortality prediction at 30 (AUC: 0.69, 95% CI 0.62-0.76 vs 0.74,
      95% CI 0.67-0.81; P = .29), 90 (AUC: 0.71, 95% CI 0.63-0.77 vs 0.74, 95% CI 0.67
      0.80; P = .52), and 180 days (AUC: 0.73, 95% CI 0.67-0.79 vs 0.75, 95% CI 0.69
      0.81; P = .66). CONCLUSION: In surgical ICU patients, PANDORA was associated with
      mortality and was comparable with APACHE II for mortality prediction at 30, 90,
      and 180 days after initiation of care. Prospective studies are needed to assess
      whether nutrition support, stratified by PANDORA scores, can improve outcomes in
      surgical ICU patients.

PMID- 30207405
TI  - The meanings of the unlicensed assistive personnel role in nursing homes: A
      triadic job analysis perspective.
AB  - AIM: This study described and analyzed how older residents, professional nurses
      and unlicensed assistive personnel (UAP) perceive the meaning and content of the
      job carried out by UAP in nursing homes (NHs), as a basis for job analysis.
      BACKGROUND: Increasing numbers of NH beds and financial restraints have led UAP
      to become a significant part of the long-term care service system, yet in
      numerous contexts, the UAP job remains misunderstood and underexplored. METHOD:
      The research employed a qualitative phenomenological methodology. Data were
      collected from 50 semi-structured in-depth interviews with 18 UAP, 15 certified
      nurses and 17 older NH residents. RESULTS: We identified six content dimensions
      in the participants' descriptions regarding the meanings of the roles and duties
      of the UAP: (a) care for the physical environment, (b) bodily-physical care, (c)
      psycho-social interpersonal care, (d) professional hierarchy and boundaries, (e)
      UAP personal traits and (f) UAP skills, or the need for training and professional
      education. CONCLUSIONS: Future job definition and formal regulation of UAP should
      place more focus on the personal characteristics of UAP, as a prerequisite to
      enter the job. IMPLICATIONS FOR NURSING MANAGEMENT: The study takes a step
      forward toward better defining the professional boundaries delineating the
      meaning of the UAP position.

PMID- 30207406
TI  - Does level of minority presence and hospital reimbursement policy influence
      hospital referral region health rankings in the United States.
AB  - The shift from a fee-for-service payment to a value-based payment scheme, sparked
      by the Patient Protection and Affordable Care Act, introduced pay-for-performance
      programs such Hospital Value Based Purchasing. Previous inquiry has not
      considered how local community factors may affect hospital system performance.
      This study investigated the association between local health performance and
      minority population in a hospital referral region (HRR). The primary objective
      was to ascertain whether community diversity levels are significantly associated
      to local health performance guided by the ecological model. Secondary data
      analysis collected from the 2016 American Hospital Association, Area Health
      Resource File, Commonwealth Fund Scorecard on Local Health System Performance,
      and the Dartmouth Atlas HRR dataset was used. Our primary findings show that the
      more diverse a HRR is, the more likely it is to be associated with lower ranking
      for access and affordability prevention and treatment avoidable hospital use and
      cost as well as healthy lives. Total performance score was significantly related
      to a better health ranking on prevention and treatment, hospital use, and cost,
      as well as healthy lives. This research supports the assertion that communities,
      particularly minorities in those communities, affect local health care
      performance in a variety of ways.

PMID- 30207407
TI  - Combining multiple imputation and bootstrap in the analysis of cost-effectiveness
      trial data.
AB  - In healthcare cost-effectiveness analysis, probability distributions are
      typically skewed and missing data are frequent. Bootstrap and multiple imputation
      are well-established resampling methods for handling skewed and missing data.
      However, it is not clear how these techniques should be combined. This paper
      addresses combining multiple imputation and bootstrap to obtain confidence
      intervals of the mean difference in outcome for two independent treatment groups.
      We assessed statistical validity and efficiency of 10 candidate methods and
      applied these methods to a clinical data set. Single imputation nested in the
      bootstrap percentile method (with added noise to reflect the uncertainty of the
      imputation) emerged as the method with the best statistical properties. However,
      this method can require extensive computation times and the lack of standard
      software makes this method not accessible for a larger group of researchers.
      Using a standard unpaired t-test with standard multiple imputation without
      bootstrap appears to be a robust alternative with acceptable statistical
      performance for which standard multiple imputation software is available.

PMID- 30207408
TI  - Pseudo-tetrahedral Rhodium and Iridium Complexes: Catalytic Synthesis of E
      Enynes.
AB  - The reactions of the rhodium(I) and iridium(I) complexes [M(PhBP3 )(C2 H4
      )(NCMe)] (PhBP3 =PhB(CH2 PPh2 )3 - ) with alkynes have resulted in the synthesis
      of a new family of pseudo-tetrahedral complexes, [M(PhBP3 )(RC=CR')] (M=Rh, Ir),
      which contain the alkyne as a four-electron donor. The reactions of these unusual
      compounds with two-electron donors (L=PMe3 , CNtBu) produced a change in the
      "donicity" of the alkyne from a 4e- to a 2e- donor to give five-coordinate
      complexes. These were the final products with the iridium complexes, whereas
      further reactions took place with the rhodium complexes. In particular, C(sp)-H
      bond activation of the alkyne occurred leading to hydrido alkynyl complexes. This
      process is essential for the further reactivity of the alkynes, and if the alkyne
      itself was used as reagent, E-enyne complexes were obtained. As a consequence of
      this chemistry, we show that the complex [Rh(PhBP3 )(C2 H4 )(NCMe)] is a very
      efficient pre-catalyst for the regioselective di- and trimerization of terminal
      alkynes to E-enynes and benzene derivatives, respectively. Interestingly,
      acetonitrile significantly enhanced the catalytic activity by facilitating the
      C(sp)-H bond activation step. A hydrometalation mechanism to account for these
      experimental observations is proposed.

PMID- 30207409
TI  - The impact of health transformation plan on hospitalization rates in Iran: An
      interrupted time series.
AB  - OBJECTIVE: The study aims to assess the impact of health transformation plan
      (HTP) as a major health system reform on hospitalization rate in Iran. Health
      transformation plan adopted different measures to increase the coverage of basic
      health insurance, increase the quality of outpatient visit care, improve and
      expand the family physician program, expand health services to suburban areas,
      reduce out-of-pocket (OOP) payments for inpatient services, and update tariffs to
      more realistic ones. METHODS: We selected Kurdistan province, a province that was
      not a patient referral hub, for the collection of monthly hospitalization data
      over a period of 50 months. Interrupted time series (ITS) analysis was carried
      out, and segmented regression analysis was employed to assess the abrupt (or
      short-term) and gradual (or long-term) effects of HTP on hospitalization rate.
      RESULTS: Although before the intervention, there was no significant increase or
      decline in hospitalization rate in the Kurdistan province, after the
      implementation of HTP, a significant increase in the intercept and slope of
      hospitalization rate was observed (P < 0.001). CONCLUSION: Health transformation
      plan has improved the utilization of hospitalization care services in a province
      that historically had been suffering from underutilized hospital services.

PMID- 30207410
TI  - Reactions of Fluoroalkanes with Mg-Mg Bonds: Scope, sp3 C-F/sp2 C-F Coupling and
      Mechanism.
AB  - sp3 C-F Bonds of fluoroalkanes (7 examples; 1 degrees , 2 degrees  and 3 degrees
      ) undergo addition to a low-valent Mg-Mg species generating reactive
      organomagnesium reagents. Further reactions with a series of electrophiles
      results in a net C-F to C-B, C-Si, C-Sn or C-C bond transformation (11 examples,
      diversity). The new reactivity has been exploited in an unprecedented one-pot
      magnesium-mediated coupling of sp3 C-F and sp2 C-F bonds. Calculations suggest
      that the sp3 C-F bond activation step occurs by frontside nucleophilic attack of
      the Mg-Mg reagent on the fluoroalkane.

PMID- 30207411
TI  - Use of Intradialytic Parenteral Nutrition in Patients Undergoing Hemodialysis.
AB  - Intradialytic parenteral nutrition (IDPN) is a form of supplemental nutrition
      used to treat patients with malnutrition who receive hemodialysis. Once the
      diagnosis of malnutrition is made in such patients, encouragement of oral intake
      is the first-line treatment. If this fails, then enteral or parenteral nutrition
      may be needed. This review examines the literature on the use of IDPN and
      summarizes the current recommendations. There is considerable controversy over
      indications and benefits of IDPN, and well-controlled, long-term studies are
      needed to help tease out these issues. In the interim, clinical judgment should
      be used when considering IDPN for individual patients.

PMID- 30207412
TI  - Histone deacetylase 2 is essential for LPS-induced inflammatory responses in
      macrophages.
AB  - The role of specific histone deacetylase (HDAC) proteins in regulating the
      lipopolysaccharide (LPS)-induced inflammatory response and its underlying
      mechanisms are unclear. Here, HDAC2, a class I HDAC family protein, is essential
      for the LPS-triggered inflammatory response in macrophages. LPS stimulation
      increases HDAC2 expression in macrophages. Knockdown of HDAC2 decreases the
      expression of proinflammatory genes, such as IL-12, TNF-alpha and iNOS following
      stimulation with LPS. The adoptive transfer of HDAC2 knockdown macrophages
      attenuates the LPS-triggered innate inflammatory response in vivo, and these mice
      are less sensitive to endotoxin shock and Escherichia coli-induced sepsis.
      Mechanistically, the c-Jun protein is the main target of HDAC2-mediated LPS
      induced production of proinflammatory cytokines. Moreover, HDAC2 knockdown
      increases the expression of c-Jun, which directly binds the promoters of
      proinflammatory genes and forms nuclear receptor corepressor complexes to inhibit
      the transcription of proinflammatory genes in macrophages. These effects are
      rescued by c-Jun expression. According to the chromatin immunoprecipitation
      analysis, HDAC2 also selectively suppresses c-Jun expression by directly binding
      to its promoter and modifying histone acetylation after LPS stimulation. Our
      findings define a new function and mechanism of the HDAC2/c-Jun signaling network
      that regulates the LPS-induced immune response in macrophages.

PMID- 30207413
TI  - Fertility Awareness Methods.

PMID- 30207414
TI  - The Borole Route to Reactive Pentafluorophenyl-Substituted Diboranes(4).
AB  - The beta-borylborole 3 adds phenylacetylene in a [4+2]-cycloaddition to give the
      boryl-substituted 7-boranorbornadiene derivative 4 b. Thermolysis (60  degrees C)
      results in a rearrangement with B-B coupling to give the tetraaryldiborane(4) 6
      b. It splits dihydrogen with cleavage of the B-B bond. With the terminal
      acetylene 1-pentyne the diborane(4) compound 6 b undergoes a rare 1,1-diboration
      reaction to yield the respective geminal diborylalkene product 14.

PMID- 30207415
TI  - Developmental processes regulate craniofacial variation in disease and evolution.
AB  - Variation in development mediates phenotypic differences observed in evolution
      and disease. Although the mechanisms underlying phenotypic variation are still
      largely unknown, recent research suggests that variation in developmental
      processes may play a key role. Developmental processes mediate genotype-phenotype
      relationships and consequently play an important role regulating phenotypes. In
      this review, we provide an example of how shared and interacting developmental
      processes may explain convergence of phenotypes in spliceosomopathies and
      ribosomopathies. These data also suggest a shared pathway to disease treatment.
      We then discuss three major mechanisms that contribute to variation in
      developmental processes: genetic background (gene-gene interactions), gene
      environment interactions, and developmental stochasticity. Finally, we comment on
      evolutionary alterations to developmental processes, and the evolution of disease
      buffering mechanisms.

PMID- 30207416
TI  - Development of School and Sport Burnout in Adolescent Student-Athletes: A
      Longitudinal Mixed-Methods Study.
AB  - We investigated the development of school and sport burnout in adolescent student
      athletes (N Time 1 = 391, N Time 2 = 373) during their first year in upper
      secondary school using an embedded mixed-methods design. The questionnaire-based
      data were analyzed with growth mixture modeling and four burnout profiles were
      identified among student-athletes. From the found burnout profiles, two were
      typical for the interviewed subsample of elite athletes (n = 17), that is,
      burnout risk and non risk profiles. We generated rich descriptions of well-being
      and ill-being, showing that elite athletes in two burnout profiles differed in
      their experienced demands and resources related to individual and environmental
      factors. The results can be used to generate practical tools for burnout
      detection in student-athletes' educational path.

PMID- 30207417
TI  - Improved exposure of the hypoglossal branches during hypoglossal nerve stimulator
      implantation: Clinical outcomes of twenty patients at a single institution.

PMID- 30207418
TI  - Effect of urbanization on soil methane and nitrous oxide fluxes in subtropical
      Australia.
AB  - Increasing population densities and urban sprawl are causing rapid land use
      change from natural and agricultural ecosystems into smaller, urban residential
      properties. However, there is still great uncertainty about the effect that
      urbanization will have on biogeochemical C and N cycles and associated greenhouse
      gas (GHG) budgets. We aimed to evaluate how typical urbanization related land use
      change in subtropical Australia affects soil GHG exchange (N2 O and CH4 ) and the
      associated global warming potential (GWP). Fluxes were measured from three land
      uses: native forest, a long-term pasture, and a turf grass lawn continuously over
      two years using a high-resolution automated chamber system. The fertilized turf
      grass had the highest N2 O emissions, dominated by high fluxes >100 g N2 O-N day
      1 immediately following establishment though decreased to just 0.6 kg N2 O-N ha-1
      in the second year. Only minor fluxes occurred in the forest and pasture, with
      the high aeration of the sandy topsoil limiting N2 O emissions while promoting
      substantial CH4 uptake. Native forest was consistently the strongest CH4 sink (
      2.9 kg CH4 -C ha-1  year-1 ), while the pasture became a short-term CH4 source
      after heavy rainfall when the soil reached saturation. On a two-year average,
      land use change from native forest to turf grass increased the non-CO2 GWP from a
      net annual GHG sink of -83 CO2 -e ha-1  year-1 to a source of 245 kg CO2 -e ha-1 
      year-1 . This study highlights that urbanization can substantially alter soil GHG
      exchange by altering plant soil water use and by increasing bulk density and
      inorganic N availability. However, on well-drained subtropical soils, the impact
      of urbanization on inter-annual non-CO2 GWP of turf grass was low compared to
      urbanized ecosystems in temperate climates.

PMID- 30207420
TI  - Substitution of artificial colloids for fresh frozen plasma in pediatric
      cardiopulmonary bypass surgery.
AB  - BACKGROUND: In many centers, fresh frozen plasma is generally used as the main
      component of pump prime in pediatric cardiopulmonary bypass. However, many
      factors have resulted in stringent control of plasma transfusion and prompted the
      study of safe and efficient substitutes. AIMS: The aim of this study was to
      investigate the feasibility of a priming strategy with gelatin during
      cardiopulmonary bypass in pediatric patients undergoing cardiac surgery and
      identify the factors associated with postoperative chest-tube drainage. METHODS:
      We reviewed 1164 pediatric patients who underwent cardiac surgery with
      cardiopulmonary bypass between January 2012 and April 2013 in Fuwai hospital.
      Infants and children were primed with different types of solution: plasma or
      gelatin. Clinical data included postoperative coagulation function
      (pharmacological agents, chest-tube drainage, and transfusion requirements),
      recovery indicators (mechanical ventilator time, ICU stay and hospital stay),
      incidence of in-hospital mortality, and morbidity. Multivariate linear regression
      analysis was used to identify factors correlated with postoperative chest-tube
      drainage. RESULTS: No difference in mortality or morbidity was found between the
      plasma and gelatin groups. In infants, increased chest-tube drainage
      (postoperation 12 hours, median difference -0.046 ml/kg/hr, 95%CI: -0.105 to 
      0.007, P = 0.001; postoperation 24 hours, median difference -0.047 ml/kg/hr,
      95%CI: -0.081 to -0.025, P < 0.001), and decreased transfusion (red blood cell,
      median difference 0.00 ml/kg/hr, 95%CI: 0.000-100, P < 0.001; fresh frozen
      plasma, median difference 5.556 ml/kg/hr, 95%CI: 2.30-8.333, P = 0.001), and
      recovery time (mechanical ventilator time, median difference 3.00 hours, 95%CI:
      1.00-5.500, P < 0.001; ICU stay, median difference 17.00 hours, 95%CI: 1.00
      22.000, P = 0.001; hospital stay, median difference 1.00 day, 95%CI: 0.00-2.000,
      P = 0.038) were demonstrated in the gelatin group. In children, the transfusion
      requirements (red blood cell, median difference 100 ml, P < 0.001;fresh frozen
      plasma, median difference 1.11 ml/kg, 95%CI: 0.000-2.42, P = 0.001) were
      decreased in the gelatin group. Multivariate linear regression analysis revealed
      that the type of priming solution (beta = 1.940,95%CI: 1.057-2.823,P < 0.001),
      bypass time (beta = 0.024, 95%CI: 0.013-0.036, P < 0.001), and age (beta = 
      0.257, 95%CI: -0.422 to -0.09, P = 0.002) were independent variables correlating
      with chest-tube drainage in infants. CONCLUSION: In the general pediatric
      patients undergoing elective cardiac surgery, substitution of gelatin for fresh
      frozen plasma in cardiopulmonary bypass is feasible.

PMID- 30207421
TI  - De Novo Malignancies Screening After Liver Transplantation for Alcoholic Liver
      Disease: A Comparative Opportunistic Study.
AB  - Patients having received a liver transplantation (LT) for alcoholic liver disease
      (ALD) have a high risk of de novo malignancies, especially in the upper
      aerodigestive tract and lungs due to their smoking and alcohol history. The aim
      of this retrospective study was to compare a group of patients transplanted for
      ALD who continue to smoke and who were included in an intensive screening program
      for tobacco-related cancers implemented at the Grenoble University Hospital and a
      group of similar patients followed according to usual practice (chest computed
      tomography [CT] scan every 5 years) at the Edouard Herriot Hospital in Lyon. The
      intensive screening program consisted of an annual checkup, including a clinical
      examination by an otorhinolaryngologist, a chest CT scan, and an upper digestive
      endoscopy. A total of 147 patients were included: 71 patients in Grenoble and 76
      patients in Lyon. The cumulative incidence of a first tobacco-related cancer was
      12.3% at 3 years, 20.6% at 5 years, 42.6% at 10 years, and 64.0% at 15 years. A
      curative treatment was possible in 80.0% of the patients in Grenoble versus 57.9%
      in Lyon (P = 0.068). The rates of curative treatment were 63.6% versus 26.3% (P =
      0.062) for lung cancers, 100.0% versus 87.5% (P = 0.498) for lip-mouth-pharynx
      and larynx cancers, and 66.7% versus 100.0% (P = 1) for esophageal cancers,
      respectively. In addition, for lung cancers, regardless of study group, 68.7%
      received a curative treatment when the diagnosis was made by CT scan screening
      versus 14.3% when it was made because of symptoms (P = 0.008). In conclusion, our
      study strongly confirms the high rate of tobacco-related de novo malignancies in
      LT patients for ALD and suggests that the screening of lung cancer by annual
      chest CT scan could significantly increase the rate of curative treatment.

PMID- 30207419
TI  - Psychosocial impact of BRCA testing in young Black breast cancer survivors.
AB  - OBJECTIVE: Prior studies demonstrating minimal psychological consequences for
      women receiving genetic counseling/genetic testing (GC/GT) for hereditary breast
      and ovarian cancer rely on predominantly Caucasian women. We conducted a
      prospective follow-up of a subset of participants from a population-based study
      of Black breast cancer (BC) survivors receiving GC/GT for BRCA1 and BRCA2
      mutations. METHODS: Black women with invasive BC at age <= 50 years diagnosed
      between 2009 and 2012 were recruited through the Florida Cancer Registry.
      Participants (n = 215, age M = 44.7, SD = 6.2) were offered telephone pre- and
      post-test GC, a subset completed questionnaires assessing sociodemographic,
      clinical, and psychosocial variables. RESULTS: There were no baseline differences
      in cancer-related distress, psychological distress, or quality of life between
      test result groups. Social well-being improved in women receiving negative
      results (P = .01), but no other outcomes demonstrated significant changes over
      time between groups. CONCLUSIONS: Our study is among the first to demonstrate
      minimal negative psychosocial outcomes following GC/GT among young Black BC
      survivors, irrespective of test results.

PMID- 30207422
TI  - Changes in Cerebral Hemodynamics in Patients With Cirrhosis After Liver
      Transplantation.
AB  - Improvement in cognitive function after orthotopic liver transplantation (LT) has
      been demonstrated in the acute setting immediately after LT and in acute liver
      failure. However, the longterm changes in cerebral hemodynamics after LT remain
      unexplored. Therefore, we aimed to evaluate the longterm changes in cerebral
      hemodynamics of patients with cirrhosis after LT. In this prospective cohort
      study, we performed transcranial Doppler ultrasonography (TCD) measuring the
      pulsatility index (PI), resistance index (RI), and breath-holding index (BHI) to
      evaluate cerebrovascular structural integrity and reactivity, respectively, in
      both middle cerebral arteries before and after LT. Neuropsychometric tests and
      West-Haven criteria were used for hepatic encephalopathy (HE) characterization.
      Interleukin 6 and tumor necrosis factor alpha plasma levels were measured.
      Descriptive statistics and Wilcoxon's test were used. There were 27 patients who
      were included. Median follow-up after LT was 6 months, mean age before LT was
      46.3 +/- 10.3 years, the main etiology was hepatitis C virus (59%), and most of
      the patients were Child-Pugh B (15/27). Model for End-Stage Liver Disease (MELD)
      score was 16 +/- 7.5, MELD-Na was 19.3 +/- 7.1, Psychometric Hepatic
      Encephalopathy Score was -3.48 +/- 3.66, and critical flicker fusion (CFF) was
      40.28 +/- 5.70 Hz. Before LT, 17/27 patients had HE and 11/27 ascites. A decrease
      of 20.8% and 13.5% in PI and RI was observed after LT (P < 0.001, both), together
      with an increase in BHI (32.4%, P = 0.122). These changes in cerebral
      hemodynamics paralleled those in systemic inflammation. Clinical improvement in
      cognition was observed in all patients with overt HE after LT. In conclusion,
      these results show a significant improvement in cerebral hemodynamics after LT,
      obtained through TCD, indicating less arterial cerebral vasoconstriction together
      with a decrease in systemic inflammation. Changes in cerebral vasoconstriction
      can be the basis for the improvement in cognitive function after LT in the long
      term.

PMID- 30207423
TI  - A behaviour change intervention with lipid-based nutrient supplements had little
      impact on young child feeding indicators in rural Kenya.
AB  - Poor infant and young child feeding (IYCF) practices are associated with linear
      growth faltering. Our objective was to evaluate the impact of a nutrition and
      water and sanitation for health intervention on three IYCF indicators-minimum
      dietary diversity (MDD), minimum meal frequency (MMF), and minimum acceptable
      diet (MAD) in Kenyan children. Households were randomized into one of eight
      groups: (a) active control; (b) passive control; (c) water quality (W); (d)
      sanitation (S); (e) handwashing (H); (f) combined Water, Sanitation, and
      Handwashing; (g) nutrition (N); and (h) combined WSH + N. In the N and WSH + N
      arms, community-based promoters counselled households on optimal IYCF practices,
      and small-quantity lipid-based nutrient supplements (SQ-LNS) were provided to
      children 6-24 months of age. Twelve months (Year 1) and 24 months (Year 2) after
      interventions began, enumerators surveyed mothers to ascertain IYCF practices. We
      made pairwise comparisons of each intervention arm versus the active control arm
      using log binomial models. In total, 3,652 caretakers were surveyed at Year 1 and
      4,987 caretakers at Year 2. Compared with the active control, there were no
      differences in any of the arms in MDD, MMF, or MAD, aside from an increase in MDD
      at Year 1 in the nutrition only arm but not in the combined WSH + N arm (N: 68%;
      WSH + N: 61%; C: 61%; N arm prevalence ratio: 1.13 95% CI [1.01, 1.25]). In this
      setting, a nutrition behaviour change communication intervention had little
      impact on IYCF indicators. The provision of SQ-LNS was not detrimental to current
      IYCF indicators in the community.

PMID- 30207424
TI  - Determining the extent of the dural sac for the performance of caudal epidural
      blocks in newborns.
AB  - BACKGROUND: Information regarding the position and relationship of vital
      structures within the caudal canal is important for anesthesiologists who perform
      a caudal block. This information can be acquired by anatomical dissection, with
      ultrasound technology, or radiological studies. AIMS: The aim of this study was
      to determine the position of the dural sac in neonates by measuring the distance
      of the termination of the dural sac from the apex of the sacral hiatus in
      neonatal cadavers. METHODS: After careful dissection, the distance from the apex
      of the sacral hiatus to the dural sac was measured in a sample of neonatal
      cadavers. RESULTS: In 39 neonatal cadavers, the mean distance from the apex of
      the sacral hiatus to the dural sac was 10.45 mm. The range of this distance was
      between 4.94 and 26.28 mm. The mean distance for females was 9.64 mm (range from
      6.66 to 15.09); that for males was 10.90 mm (range between 4.94 and 26.28).
      Linear regression with the log of this distance as the outcome variable gave an
      estimated 3.3% increase in the distance for each 1 cm increase in the length of
      the neonate (95% CI for this proportion was 1.91-4.71). CONCLUSION:
      Anesthesiologists should be aware of the short distance between the sacral hiatus
      and the dural sac when performing caudal blocks, the shortest distance was 4.94
      mm. Armed with this knowledge, caudal techniques should be modified to improve
      the safety and reduce the risk of complications, such as dural puncture.

PMID- 30207425
TI  - Intergenerational influences on childhood anaemia.
AB  - Prior research on assessing intergenerational influences on child anaemia has
      largely approached it from purely maternal perspective. Although there is much
      merit to focus on that, it is an extremely limited/reductionist view of
      understanding intergenerational influences. We expanded the intergenerational
      influences to include the fathers and overall of intergenerational household
      transfers. We analysed a sample of 19,619 mother-father-offspring trios from the
      2015-2016 Indian National Fertility and Health Survey with available data on
      haemoglobin (Hb). Multinomial logistic regression models were used to establish
      associations between parent anaemia, household characteristics, and categories of
      offspring anaemia. Maternal and paternal Hb was measured as in children using a
      finger prick blood sample. The primary outcome was child's Hb level (in g/dl) and
      grades of anaemia defined as mild (10-10.9 g/dl), moderate (7-9.9 g/dl), and
      severe (<7 g/dl). Mean Hb was 10.1 g/dl for children, 14.2 g/dl among fathers,
      and 11.4 g/dl among mothers. Hb correlation was 0.1 between fathers and offspring
      and 0.2 between mothers and offspring (P < 0.001 for all correlations). Maternal
      paternal Hb correlations were consistent across quintiles of wealth index.
      Maternal anaemia was associated with odds ratio of 1.3 (95% CI [1.1, 1.4]) and
      1.6 (95% CI [1.4, 1.7]) for childhood mild and moderate/severe anaemia,
      respectively. Paternal mild anaemia was associated with an odds ratio of 1.1 (95%
      CI [0.9, 1.4]) and 1.4 (95% CI [1.2, 1.7]) for child moderate/severe anaemia. The
      clustering of poor circumstances suggests that public health strategies target
      social deprivation at the household level. A comprehensive perspective will
      provide holistic interventions to control childhood anaemia.

PMID- 30207426
TI  - Development, validation and application to real samples of a liquid
      chromatography with tandem mass spectrometry method for the determination of
      tetracyclines in beeswax.
AB  - Beeswax is a valuable honeybee product, which finds applications in the food and
      pharmaceutical industries, as well as in cosmetic production. However, some
      substances used in apiculture, like tetracyclines, can be delivered to hives
      where they cause contamination of honeybee products such as beeswax.
      Tetracyclines are commonly used for the treatment of American and European
      foulbrood diseases, but in the European Union their usage by beekeepers is
      forbidden. Thus, a sensitive method for the analysis of tetracyclines in beeswax
      is an important analytical tool. A new liquid chromatography with tandem mass
      spectrometry method for the analysis of tetracyclines including oxytetracycline,
      4-epioxytetracycline, tetracycline, 4-epitetracycline, chlorotetracycline, 4
      epichlorotetracycline, and doxycycline in beeswax was developed. The method
      involved dilution of beeswax in n-hexane after a melting step, liquid-liquid
      extraction with oxalic acid and clean-up using a weak cation exchange phase.
      Satisfactory separation was performed on an octadecyl column with 0.1% formic
      acid and acetonitrile in a total run time of 5 min. The application of this
      method was evaluated by the analysis of real beeswax samples. The presence of
      oxytetracycline was confirmed in 5 out of 48 tested beeswax samples, which shows
      the method can be successfully used to determine the tetracyclines in beeswax.

PMID- 30207427
TI  - Application of a micro plasma collection card for the detection of homocysteine
      by liquid chromatography with tandem mass spectrometry.
AB  - Generally, it is recommended that blood samples for homocysteine detection should
      be centrifuged immediately to separate plasma in order to avoid continuous
      synthesis by blood cells. The use of a micro plasma collection card may improve
      sample stability and result accuracy by offering automatic and instant plasma
      separation. We compare a micro plasma collection method with routine wet plasma
      to explore applications of the dried plasma spots for homocysteine determination
      by using liquid chromatography with tandem mass spectrometry. The method was
      validated for both dried plasma spots and wet plasma. The assay was linear from
      0.5-45 MUmol/L with good precisions and accuracies. The extraction recovery and
      matrix effect for dried plasma spots were >97% and 0.98 after internal standard
      normalization, respectively. It was reproducible for retaining homocysteine in
      dried plasma spots and kept stable for 30 days. The plasma conversion factor was
      7.77 +/- 0.7% by calculating the ratio of homocysteine concentration between
      dried plasma spots and wet plasma (n = 165). Neither hematocrit nor homocysteine
      concentration affected the plasma conversion factor as long as the hematocrit was
      within the normal range. The results support the clinical usefulness of the dried
      plasma spots as a convenient and stable biological matrix for testing
      homocysteine.

PMID- 30207430
TI  - Bronchoscopic and histologic findings during lymphatic intervention for plastic
      bronchitis.
AB  - BACKGROUND: Percutaneous lymphatic intervention (PCL) is a promising new therapy
      for plastic bronchitis (PB). We characterized bronchoalveolar lavage (BAL) and
      cast morphology in surgically repaired congenital heart disease (CHD) patients
      with PB during PCL. We quantified respiratory and bronchoscopic characteristics
      and correlated them with post-intervention respiratory outcomes. METHODS: We
      retrospectively reviewed patients with PB and surgically repaired CHD undergoing
      PCL and bronchoscopy at our institution. Pre-intervention characteristics,
      bronchoscopy notes, BAL cell counts, virology, and cultures were collected. A
      pathologist blinded to clinical data reviewed cast specimens. Respiratory
      outcomes were evaluated through standardized telephone questionnaire. RESULTS:
      Sixty-two patients were included with a median follow-up of 20 months. No
      patients experienced airway bleeding, obstruction, or prolonged intubation
      related to bronchoscopy. Of BAL infectious studies, the positive results were 4
      (8%) fungal, 6 (11%) bacterial, and 6 (14%) viral. Median BAL count per 100 cells
      for neutrophils, lymphocytes, and eosinophils were 13, 10, and 0, respectively.
      Of 23 bronchial casts analyzed, all contained lymphocytes, and 19 (83%) were
      proteinaceous, with 14 containing neutrophils and/or eosinophils. Median BAL
      neutrophil count was greater in patients with proteinaceous neutrophilic or
      eosinophilic casts compared to casts without neutrophils or lymphocytes (P =
      0.030). Post-intervention, there was a significant reduction in respiratory
      medications and support and casting frequency. CONCLUSIONS: The predominance of
      neutrophilic proteinaceous casts and high percentage of positive BAL infectious
      studies support short-term fibrinolytic and anti-infective therapies in PB in
      select patients. Flexible bronchoscopy enables safe assessment of cast burden.
      PCL effectively treats PB and reduces respiratory therapies.

PMID- 30207429
TI  - Quantitative Systems Pharmacology Model for Alzheimer Disease Indicates Targeting
      Sphingolipid Dysregulation as Potential Treatment Option.
AB  - Alzheimer disease (AD) is a devastating neurodegenerative disorder with high
      unmet medical need. Drug development is hampered by limited understanding of the
      disease and its driving factors. Quantitative Systems Pharmacology (QSP) modeling
      provides a comprehensive quantitative framework to evaluate the relevance of
      biological mechanisms in the context of disease and to predict the efficacy of
      novel treatments. Here, we report a QSP model for AD with a particular focus on
      investigating the relevance of dysregulation of cholesterol and sphingolipids. We
      show that our model captures the modulation of several biomarkers in subjects
      with AD, as well as the response to pharmacological interventions. We evaluate
      the impact of targeting the sphingosine-1-phosphate 5 receptor (S1PR5) as a
      potential novel treatment option for AD, and model predictions increase our
      confidence in this novel disease pathway. Future applications for the QSP model
      are in validation of further targets and identification of potential treatment
      response biomarkers.

PMID- 30207431
TI  - Fabrication of a Mo-Doped Strontium Cobaltite Perovskite Hybrid Supercapacitor
      Cell with High Energy Density and Excellent Cycling Life.
AB  - Enriched with oxygen vacancies, Mo-doped strontium cobaltite (SrCo0.9 Mo0.1 O3
      delta , SCM) is synthesized as an oxygen anion-intercalated charge-storage
      material through the sol-gel method. The supplemented oxygen vacancies, good
      electrical conductivity, and high ion diffusion coefficient bestow the SCM
      electrode with excellent specific capacitance (1223.34 F g-1 ) and specific
      capacity (168.88 mAh g-1 ) at 1 A g-1 . The decisive constant (b-value) deduced
      for the charge storage mechanism (low scan-rate region) is nearly 0.8, indicating
      a highly capacitive process. In the high scan-rate region, however, the b-value
      is almost 0.5, and a linear pattern of charge (q) versus the inverse of the
      square root of the scan rate (v-1/2 ) is obtained. The results reveal O2-
      diffusion as the rate-limiting factor for charge storage. Furthermore, a hybrid
      cell (SCM?LRGONR) is fabricated by using lacey, reduced graphene oxide nanoribbon
      (LRGONR) as the negative electrode, which exhibits a high energy density (74.8 Wh
      kg-1 at a power density of 734.5 W kg-1 ). With a charging time of only 20.7 s,
      the cell sustains a very high energy density (33 Wh kg-1 ) with a high power
      delivery rate (6600 W kg-1 ). The excellent cycling stability (165.1 % activated
      specific capacitance retention and 97.6 % of the maximum value attained) after 10
      000 charge-discharge cycles, demonstrates SCM is a potential electrode material
      for supercapacitors.

PMID- 30207432
TI  - A systematic review of structural equation modelling in nursing research.
AB  - BACKGROUND: A growing number of nursing studies have used structural equation
      modelling (SEM) analysis. However, there is little research assessing the use of
      SEM analysis in nursing research. AIM: To present a systematic review of nursing
      research that uses SEM. DISCUSSION: The review revealed poor reporting of
      information about the determination of sample size, missing data, normality and
      outliers. Most studies neither computed composite reliability nor assessed
      convergent and discriminant validity. There was a lack of consistency in
      performing the analysis. Some of the studies conducted exploratory factor
      analysis before performing confirmatory factor analysis, without discussing its
      necessity. Although most studies declared the estimation method and software
      used, there were many that did not. CONCLUSION: Little information about the
      different steps of conducting SEM analysis was provided in the studies.
      Weaknesses and areas of improvement for future empirical SEM studies were
      identified. IMPLICATIONS FOR PRACTICE: When conducting SEM, there are many issues
      that should be addressed. Overlooking these issues may invalidate findings. The
      results of this review provide nurse researchers with best practice guidelines
      for conducting SEM and pave the way for researchers to adopt this method in their
      studies.

PMID- 30207433
TI  - Minimally invasive approaches to aneurysms of the anterior circulation: selection
      criteria and clinical outcomes.
AB  - Over the last few decades, cerebrovascular surgery has gravitated towards a
      minimally invasive philosophy without compromising the foundational principles of
      patient safety and surgical efficacy. Enhanced radiosurveillance modalities and
      increased average life expectancy have resulted in an increased reported
      incidence of intracranial aneurysms. Although endovascular therapies have gained
      popularity in the recent years, microsurgical clipping continues to be of value
      in the management of these aneurysms owing to its superior occlusion rates,
      applicability to complex aneurysms and reduced retreatment rates. The concept of
      keyhole transcranial procedures has advanced the field significantly leading to
      decreased post-operative neurological morbidity and quicker recovery. The main
      keyhole neurosurgical approaches include the supraorbital craniotomy (SOC),
      lateral supraorbital craniotomy (LSOC), mini-pterional craniotomy (MPTC), mini
      orbitozygomatic craniotomy and the mini anterior interhemispheric approach
      (MAIA). As these minimally invasive approaches can have an inherent limitation of
      a narrow viewing angle and low regional illumination, the use of endoscopic
      assistance in such procedures is being popularized. Neuroendoscopy can aid in the
      visualization of hidden neurovascular structures and inspection of the parent
      arterial segment without undue retraction of the lesion. This review focuses on
      the historical progression of the surgical management of intracranial aneurysms,
      the technical details of various minimally invasive approaches, patient selection
      and clinical outcomes of the anterior circulation aneurysms and useful tenets to
      avoid complications during these procedures. Meticulous preoperative planning to
      understand the patient's vascular anatomy, the orientation and relationship of
      the aneurysm to adjacent structures, use of neuronavigation guidance and
      endoscopic assistance if needed can lead to an optimal surgical outcome while
      minimizing neurological morbidity and mortality.

PMID- 30207434
TI  - Endophytic Yeasts in Malus domestica and Pyrus communis Fruits under
      Anthropogenic Impact.
AB  - Yeast abundance and species diversity on the surface and in inner tissues of
      Malus domestica andPyrus communis fruits under high anthropogenic impact in the
      city of Moscow (Russia) were studied. Resultsdemonstrated that abundance of
      epiphytic yeasts on the fruits increased gradually, reaching the maximum of3.2 *
      104 CFU/g on mature fruits. During summer, abundance of endophytes did not change
      significantly(variation near 2.5 * 103 CFU/g) until complete maturation, while in
      September their numbers increased to104 CFU/g. Basidiomycetous yeasts
      (Filobasidium wieringae, F. magnum, Rhodotorula glutinis, and
      Rhodosporidioboluscolostri) predominated on the fruit surface. Ascomycetous
      species were the most diverse groupinside the fruits, which quantitatively
      increased through maturation. It was found that the share of opportunisticspecies
      Candida parapsilosis in internal tissues was significant during the entire period
      of fruit formationand development under anthropogenic impact in the city.
      Specific properties of epiphytic and endophyticyeast communities developing in
      natural ecological niches under synanthropic conditions and anthropogenicimpact
      are discussed.

PMID- 30207435
TI  - Analysis of chitinase diversity in the Baltic Sea bottom sediments.

PMID- 30207436
TI  - Cause analysis of dizziness in community population and research on coping
      strategies.

PMID- 30207437
TI  - Periodontitis and the microbiome: a systematic review and meta-analysis.
AB  - INTRODUCTION: The association between the oral microbiome and periodontal
      diseases is still unclear. We performed a systematic review and meta-analysis to
      quantify the association between the specific pathogens and periodontitis.
      EVIDENCE ACQUISITION: A computerized medical search was performed using MEDLINE
      and SCOPUS database between 1950 and May 2017 to identify all case-control
      studies that evaluated the association between specific pathogens and
      periodontitis. The pooled Odds Ratio with relative 95% confidence interval (95%
      CI) was calculated and plotted in the forest plot. EVIDENCE SYNTHESIS: Eleven
      RCTs involving 2111 patients were included. The retrieved case-control studies
      evaluated the presence or absence of different targeted pathogens. Among the
      microrganisms evaluated Porphyromonas gengivalis (OR [95% CI] 2.93 [0.98,8.87];
      P<0.0001) and Streptococcus mutans (OR [95% CI] 1.77 [0.89-3.54]; P=0.03) were
      found to be risk factors for the development of periodontitis, while
      Aggregatibacter actinomycetemcomitans (OR [95% CI] 0.52 [0.33-0.83]) played a
      protective role for periodontitis. CONCLUSIONS: It seems that changes in the
      taxonomic composition of the microbiome rather than single targeted pathogens is
      the key determinant of periodontitis.

PMID- 30207438
TI  - Clinical and confocal evaluation of avenanthramides-based daily cleansing and
      emollient cream in pediatric population affected by atopic dermatitis and
      xerosis.
AB  - BACKGROUND: Xerosis and atopic dermatitis (AD ) are chronic skin conditions that
      occur in children and adults which can result in scaling, flaking and itching.
      Risk factors for xerosis include sunlight, friction, low humidity and use of
      soaps. Xerosis is also a symptom of cutaneous conditions such as psoriasis,
      dermatitis and ichthyosis. AD has a complex pathogenesis but there is increased
      evidence that a genetically-impaired skin barrier plays a primary role in its
      development. METHODS: The aim of this study is to evaluate the efficacy of the
      combination of a product for topical application to be used for daily cleansing
      and an emollient cream with colloidal oatmeal, avenanthramides, shea butter and
      oat oil in patients with xerosis and AD . Indeed, emollients play a key role in
      the treatment of xerosis and of mild to moderate AD because help to restore and
      maintain the skin barrier function. Topical emollients are considered first-line
      treatment in those conditions. Outcomes included Investigators' Global Assessment
      (IGA) (0=clear, 5=very severe), Eczema Area and Severity Index (EASI) composite
      score, Itch severity (0=none, 4=severe), and Infant's Dermatitis Quality of Life
      Index (IDQOL). The evaluation of the response to treatment was also measured
      through the use of photographic documentation and examination by Reflectance
      Confocal Microscopy (RCM) performed at baseline and after therapy. RESULTS: The
      evaluation of the response to treatment was also measured through the use of
      photographic documentation and examination by reflectance confocal microscopy
      (RCM) performed at baseline and after therapy. Our results showed improvement in
      epidermal thickness, skin dryness, itching and cracking after one month of use of
      the oat cleanser and lotion. CONCLUSIONS: Colloidal oatmeal has been shown to
      safely reduce itching and irritation associated with AD and the severity of dry
      skin. These benefits, mediated by colloidal oatmeal's natural components, help to
      restore and maintain skin barrier function. This compound is safe, well
      tolerated, and can be effective as adjuvant treatment in AD . Moisturizers can
      reduce the dependency on topical corticosteroids and their potential adverse
      effects.

PMID- 30207439
TI  - Functioning and Disability in Leprosy.
AB  - This study has been carried out to investigate the frequency of musculoskeletal
      symptoms in people affected by leprosy and correlate this to their functional
      capacity to perform daily living and working activities and to their degree of
      disability. This cross-sectional study was performed on 100 clients who answered
      a questionnaire on personal and clinical data, the Nordic Musculoskeletal (QNSO),
      and the shoulder, arm andhand dysfunction (DASH) questionnaires. The mean age was
      53.63 years and there was a predominance of men (67%), low education (53%), and
      multibacillary disease (84%). Physical impairment affected 95% of respondents and
      92% indicated pain and/or paresthesia in the arms that interfered in functional
      capacity.Respondents with musculoskeletal symptoms have more difficulty to
      perform daily living and working activities compared to those without
      musculoskeletal symptoms (p-value<0.05). The presence of physical disabilities
      was not associated with difficulties to perform daily living (p-value=0.29) and
      labor activities (p-value=0.87). The majority of patients experienced pain and/or
      paresthesia of the arms, and this wasassociated with difficulties to perform
      daily living and working activities. However, the presence of physical disability
      does not seem to cause major impediments or limitations to perform these
      activities.

PMID- 30207440
TI  - Evaluation of anti-bacterial activity of Rifapentine, Clarithromycin,
      Minocycline, Moxifloxacin, Ofloxacin and their combinations in Murine Model of
      Rifampicin Resistant Leprosy.
AB  - Leprosy, a debilitating disease of the skin and peripheral nerves is caused by
      Mycobacterium leprae (M. leprae) and is treated by multidrug therapy (MDT)
      comprising of Dapsone, Rifampicin and Clofazimine. Resistance to any of these
      drugs poses a threat to the current disease control strategies. With the
      emergence of Rifampicin resistance in leprosy, it is important that alternative
      drugs need to be tested to develop a treatment strategy to combat drug resistant
      leprosy. In the current study, we have investigated WHO MDT, Rifapentine,
      Clarithromycin, Minocycline, Moxifloxacin, Ofloxacin and their combinations in
      intermittent and daily dose regimens in rifampicin resistant strains of M. leprae
      through mouse foot pad experiments in order to determine the loss in viability of
      M. leprae in response to these drugs and their combinations. Our findings suggest
      that WHO MDT is still the best combination in Rifampicin resistance cases.
      Combination of Moxifloxacin with Minocycline and Clarithromycin may also be taken
      up for clinical trials in cases with Rifampicin resistant leprosy. Rifapentine
      and Moxifloxacin can be effective alternative drugs to replace Rifampicin where
      required either in daily dose shorter duration regimens or intermittent dose
      longer regimen to treat resistant strains.

PMID- 30207441
TI  - Evaluation of New Antibacterial Drugs and their Combinations in a Murine Model to
      Identify Short Duration Alternative Chemotherapy for Leprosy.
AB  - The objective of the research is to test the efficacy of new drugs and drug
      combinations in mice infected with Mycobacterium leprae (M. leprae) as
      alternative to current WHO MDT. Individual drugs tested were Rifampicin (RMP),
      Rifapentine (RPT) and Moxifloxacin (MOXI). Drug combinations were RMP,
      Clarithromycin (CLARI), Minocycline (MINO) and RMP, MINO and Ofloxacin (OFLO).
      RPT drug combinations were RPT, CLARI,MINO and RPT, OFLO, MINO. Both the drugs
      and drug combinations were used as daily regimen and intermittent regimen. WHO MB
      MDT served as a positive control. Mice pre-inoculated with M. leprae were
      allotted to daily and intermittent groups and administered selected drugs and
      drug combinations. At the end of 12 months post sub-inoculation, mice were
      sacrificed and the proportion % of viable bacilli were counted using Spearman and
      Karber method. It was noted that RMP, RPT and Moxifloxacin indicated a range of
      89.99% to 99.99% bactericidal effect when used in daily or intermittent doses in
      both normal and TR mice. Drug combinations showed bactericidal effect comparable
      to that of WHO MDT. From the study it was concluded that if the present duration
      of MDT has to be shortened then daily dose regimen with RMP/MINO/OFLO or
      RPT/CLARI/MINO are recommended for a clinical trial.

PMID- 30207442
TI  - Cutaneous Sarcoidosis Misdiagnosed as Leprosy. Report of Two Cases and Review of
      Literature.
AB  - Cutaneous sarcoidosis may occasionally be mistaken and treated for leprosy. We
      present two cases of sarcoidosis of the skin which were initially treated as
      leprosy based on the histopathological features. Histological study in one
      patient showed perineural and perivascular granuloma adding on to the diagnostic
      confusion. It is very important for the clinicians to consider sarcoidosis as a
      possible diagnosis in a patient with clinical features that are not typical of
      leprosy. Histopathology along with appropriate in -situ techniques can help in
      arriving at an appropriate diagnosis.

PMID- 30207443
TI  - Pityriasis Rosea Localized to the Skin Patches of Leprosy. A Wolf's Isotopic
      Response?
AB  - Pityriasis rosea is one of the commonly encountered papulo squamous disease in
      dermatology outpatient department. Its clinical presentations are varied, and it
      also has many atypical forms. We report a case of a male patient with classical
      Pityriasis rosea lesions limited to the patches of Hansen's disease. This is
      probably being reported for the first time in literature.

PMID- 30207444
TI  - Theoretical Overview of Methane Hydroxylation by Copper-Oxygen Species in
      Enzymatic and Zeolitic Catalysts.
AB  - As fossil-based energy sources become more depleted and with renewable-energy
      technologies still in a very early stage of development, the utilization of
      highly abundant methane as a transitional solution for current energy demands is
      highly important despite difficulties in transport and storage. Technologies
      enabling the conversion of methane to liquid/condensable energy carriers that can
      be easily transported and integrated into the existing chemical infrastructures
      are therefore essential. Although there commercially exists a two-step gas-to
      liquid process involving syngas production, a novel route of methane conversion
      that can circumvent the high-cost production of syngas should be developed. Among
      all of the conceptually possible methods for converting methane to methanol,
      methane hydroxylation (CH4 + 1/2O2 -> CH3OH) at low temperature seems to be the
      most viable since it provides a direct route of conversion and allows a much
      lower operational cost. However, it is hampered by the fact that the complete
      oxidation to CO2 is thermodynamically more favored. To overcome this, an
      effective catalyst that is able to "mildly" oxidize methane and stabilize the
      resultant methyl radical toward methanol formation is required. Particulate
      methane monooxygenase (pMMO) and copper-exchanged zeolites are two catalysts
      known to hydroxylate methane into methanol at low temperature with high
      selectivity. Having been studied for more than 30 years, these copper-cored
      catalysts are still relevant topics of discussion since the actual structure of
      the active sites has not been agreed upon, and thus, the reaction mechanism and
      factors influencing their reactivity and productivity are yet to be understood.
      Density functional theory (DFT) has provided us with a powerful computational
      tool for accomplishing these tasks. This Account presents an overview of the
      recent progress in the computational elucidation of the catalytic mechanism of
      methane hydroxylation by mono-, di-, and trinuclear copper sites in pMMO and Cu
      exchanged zeolites as well as its correlations to the influencing factors that
      must be controlled to achieve higher reactivity. First, we briefly introduce the
      catalytic mechanism of a bare CuO+ cation as the simplest copper-oxo system in
      methane hydroxylation. The system is then extended to the copper-oxo species in
      pMMO and zeolites, and the radical and nonradical mechanisms are examined.
      Investigations of the reactivities of mononuclear and dinuclear copper-oxo
      species in the pMMO active site suggest that the bis(MU-oxo)CuIICuIII, (MU
      oxo)(MU-hydroxo)CuIICuIII, and CuIIIO species are important for the catalytic
      activity of pMMO. In the case of Cu-exchanged zeolites, as the mono(MU
      oxo)CuIICuII and tris(MU-oxo)CuIICuIIICuIII active sites have been fully
      characterized in experiments, here we discuss the effects of zeolite structures
      on the geometry and reactivity of the active sites.

PMID- 30207445
TI  - Multistage Chemical Heating for Instrument-Free Biosensing.
AB  - Improving the portability of diagnostic medicine is crucial for alleviating
      global access-to-care deficiencies. This requires not only designing devices that
      are small and lightweight, but also autonomous and independent of electricity.
      Here, we present a strategy for conducting automated multistep diagnostic assays
      using chemically generated, passively regulated heat. Ligation and polymerization
      reagents for rolling circle amplification of nucleic acids are separated by
      meltable phase-change partitions, thus replacing precise manual reagent additions
      with automated partition melting. To actuate these barriers and individually
      initiate the various steps of the reaction, field ration heaters exothermically
      generate heat in a thermos, whereas fatty acids embedded in a carbonaceous matrix
      passively buffer the temperature around their melting points. Achieving
      multistage temperature profiles extend the capability of instrument-free
      diagnostic devices and improve the portability of reaction automation systems
      built around phase-change partitions.

PMID- 30207446
TI  - Sensitive and Robust Ultraviolet Photodetector Array Based on Self-Assembled
      Graphene/C60 Hybrid Films.
AB  - Graphene has been widely investigated for use in high-performance photodetectors
      due to its broad absorption band and high carrier mobility. While exhibiting
      remarkably strong absorption in the ultraviolet range, the fabrication of a large
      scale integrable, graphene-based ultraviolet photodetector with long-term
      stability has proven to be a challenge. Here, using graphene as a template for
      C60 assembly, we synthesized a large-scale all-carbon hybrid film with inherently
      strong and tunable UV aborption. Efficient exciton dissociation at the
      heterointerface and enhanced optical absorption enables extremely high
      photoconductive gain, resulting in UV photoresponsivity of ~107 A/W.
      Interestingly, due to the electron-hole recombination process at the
      heterointerface, the response time can be modulated by the gate voltage. More
      importantly, the use of all-carbon hybrid materials ensures robust operation and
      further allows the demonstration of an exemplary 5 * 5 (2-dimensional)
      photodetector array. The devices exhibit negligible degradation in figures of
      merit even after 2 month of operation, indicating excellent environmental
      robustness. The combination of high responsivity, reliability, and scalable
      processability makes this new all-carbon film a promising candidate for future
      integrable optoelectronics.

PMID- 30207447
TI  - Ultrarapid and Deep Debromination of Tetrabromodiphenyl Ether over Noble-Metal
      Free Cu/TiO2 Nanocomposites under Mild Conditions.
AB  - Fast and deep debromination of polybrominated diphenyl ethers (PBDEs) under mild
      conditions is a challenge in the field of pollution control. A strategy was
      developed to achieve it by exploiting Cu/TiO2 composites as a noble-metal-free
      catalyst. Toward the debromination of 2,2',4,4'-tetrabromodiphenyl ether (BDE47)
      as a typical PBDE, the use of Cu/TiO2 as a catalyst and hydrazine hydrate
      (N2H4.H2O) as a reducing agent yielded a degradation removal of 100% and a
      debromination efficiency of 87.7% in 3 s. A complete debromination of BDE47 at
      1500 mg L-1 was possible by successively adding N2H4.H2O. A debromination pathway
      involving active H atom species was proposed for the catalytic transfer
      hydrogenation (CTH) of PBDEs according to the identified degradation
      intermediates. A mechanism was further clarified by density functional theory
      calculations: electrons are delivered from N2H4.H2O to the metallic Cu atom via a
      coordination of N in N2H4.H2O with Cu atoms. The electron-trapped Cu atom
      interacts with adsorbed BDE47 to form a transition complex, and then the
      debromination of this complex occurs on the surface of Cu nanoparticles due to
      the hydrogen donation of N2H4.H2O through the CTH process. The new method
      provides a highly efficient method to remove brominated pollutants.

PMID- 30207448
TI  - Synthetic Nanomotors: Working Together through Chemistry.
AB  - Active matter, some of whose constituent elements are active agents that can move
      autonomously, behaves very differently from matter without such agents. The
      active agents can self-assemble into structures with a variety of forms and
      dynamical properties. Swarming, where groups of living agents move cooperatively,
      is commonly observed in the biological realm, but it is also seen in the physical
      realm in systems containing small synthetic motors. The existence of diverse
      forms of self-assembled structures has stimulated the search for new applications
      that involve active matter. We consider active systems where the agents are
      synthetic chemically powered motors with various shapes and sizes that operate by
      phoretic mechanisms, especially self-diffusiophoresis. These motors are able to
      move autonomously in solution by consuming fuel from their environment. Chemical
      reactions take place on catalytic portions of the motor surface and give rise to
      concentration gradients that lead to directed motion. They can operate in this
      way only if the chemical composition of the system is maintained in a
      nonequilibrium state since no net fluxes are possible in a system at equilibrium.
      In contrast to many other active systems, chemistry plays an essential part in
      determining the properties of the collective dynamics and self-assembly of these
      chemically powered motor systems. The inhomogeneous concentration fields that
      result from asymmetric motor reactions are felt by other motors in the system and
      strongly influence how they move. This chemical coupling effect often dominates
      other interactions due to fluid flow fields and direct interactions among motors
      and determines the form that the collective dynamics takes. Since we consider
      small motors with micrometer and nanometer sizes, thermal fluctuations are strong
      and cannot be neglected. The media in which the motors operate may not be simple
      and may contain crowding agents or molecular filaments that influence how the
      motors assemble and move. The collective motion is also influenced by the
      chemical gradients that arise from reactions in the surrounding medium. By
      adopting a microscopic perspective, where the motors, fluid environment, and
      crowding elements are treated at the coarse-grained molecular level, all of the
      many-body interactions that give rise to the collective behavior naturally emerge
      from the molecular dynamics. Through simulations and theory, this Account
      describes how active matter made from chemically powered nanomotors moving in
      simple and more complicated media can form different dynamical structures that
      are strongly influenced by interactions arising from cooperative chemical
      reactions on the motor surfaces.

PMID- 30207449
TI  - Chemical Protective Textiles of UiO-66-Integrated PVDF Composite Fibers with
      Rapid Heterogeneous Decontamination of Toxic Organophosphates.
AB  - Metal-organic frameworks (MOFs) are a new and growing area of materials with high
      porosity and customizability. UiO-66, a zirconium-based MOF, has shown much
      interest to the military because of the ability of the MOF to catalytically
      decontaminate chemical warfare agents (CWAs). Unfortunately, the applications for
      MOFs are limited because of their powder form, which is difficult to incorporate
      into protective clothing. As a result, a new area of research has developed to
      functionalize fabrics with MOFs to make a wearable multifunctional fabric that
      retains the desired properties of the MOF. In this work, UiO-66 was incorporated
      into poly(vinylidene) fluoride/Ti(OH)4 composite fabric using electrospinning and
      evaluated for its use in chemical protective clothing. The base triethanolamine
      (TEA) was added to the composite fabric to create a self-buffering system that
      would allow for catalytic decontamination of CWAs without the need for a buffer
      solution. The fabrics were tested against the simulants methyl-paraoxon (dimethyl
      (4-nitrophenyl) phosphate, DMNP), diisopropyl fluorophosphate (DFP), and the
      nerve agent soman (GD). The results show that all of the samples have high
      moisture vapor transport and filtration efficiency, which are desirable for
      protective clothing. The incorporation of TEA decreased air permeation of the
      fabric, but increased the catalytic activity of the composite fabric against DMNP
      and DFP. Samples with and without TEA have rapid half-lives ( t1/2) as short as
      35 min against GD agent. These new catalytically active self-buffering
      multifunctional fabrics have great potential for application in chemical
      protective clothings.

PMID- 30207450
TI  - Nanostructured Li-Rich Fluoride Coated by Ionic Liquid as High Ion-Conductivity
      Solid Electrolyte Additive to Suppress Dendrite Growth at Li Metal Anode.
AB  - Blending additive with electrolyte is a facile and effective method to suppress
      anode dendrite growth in Li metal batteries (LMBs), especially when a LiF-rich
      solid electrolyte interface (SEI) is formed as a consequence of additive
      decomposition or deposition. However LiF still suffers from poor bulk ion
      conductivity as well as the difficult access to tailored nanostructure. Exploring
      new Li fluoride of high Li-ion conductivity as SEI component is still a big
      challenge in view of the lacking of desired structure prototype or mineral phase.
      Here, we propose a Li-rich Li3AlF6 derivative from cryolite phase as solid
      electrolyte additive, which is characterized by textured nanoporous morphology
      and ionic liquid coating. Its room temperature ion conductivity is as high as ~10
      5 S/cm with a low activation energy of 0.29 eV, the best level among fluoride
      based solid electrolytes. These features guarantee a homogenization of Li+
      fluxing through bulk and grain boundary of Li3AlF6-rich SEI and reinforce the
      effect on Li dendrite suppression. Li3AlF6 additive enables a stable cyclability
      of Li?Li symmetric cells for at least 100 cycles even under a high areal capacity
      of 3 mA h/cm2 and a significant improvement on capacity retention for various
      LMBs based on LiFePO4, FeS2, and S cathodes.

PMID- 30207451
TI  - Hydrogenated Na2Ti3O7 Epitaxially Grown on Flexible N-Doped Carbon Sponge for
      Potassium-Ion Batteries.
AB  - With its inherent zig-zag layered structure and open framework, Na2Ti3O7 (NTO) is
      a promising anode material for potassium-ion batteries (KIBs). However, its poor
      electronic conductivity caused by large band gap (~3.7 eV) usually leads to low
      performance KIBs. In this work, we synthesize the fluff-like hydrogenated
      Na2Ti3O7 (HNTO) nanowires grown on N-doped carbon sponge (CS) as a binder-free
      and current-collector-free flexible anode for KIBs (denoted as HNTO/CS). High
      resolution X-ray photoelectron spectroscopy (XPS) and electron spin-resonance
      spectroscopy (ESR) confirm the existence of Ti-OHs and O vacancies in HNTO. The
      first-principles calculation discloses that both Ti-OHs and O vacancies are
      equivalent to n-type doping because they can shift the Fermi level up to the
      conduction band, thus leading to a higher electronic conductivity and better
      performance for KIBs. In addition, the N-doped CS can further reinforce the
      conductivity and avoid the aggregation of HNTO nanowires during cycling. As a
      result, the as-made HNTO/CS can deliver a capacity of 107.8 mAh g-1 at 100 mA g-1
      after 20 cycles, and keep the capacity of 90.9% and 82.5% after 200 and 1555
      cycles, respectively, much better than the samples without hydrogenation
      treatment or N-doped CS and reported KTi xO y-based materials. Our work
      highlights the importance of hydrogenation treatment and N-doped CS in enhancing
      the electrochemical property for KIBs.

PMID- 30207452
TI  - Distinct Mechanosensing of Human Neural Stem Cells on Extremely Limited
      Anisotropic Cellular Contact.
AB  - Human neural stem cells (hNSCs) can alter their fate choice in response to the
      biophysical cues provided during development. In particular, it has been reported
      that the differentiation of neural stem cells (NSCs) is enhanced by anisotropic
      contact, which facilitates focal adhesion (FA) formation and cytoskeletal
      organization. However, a biomolecular mechanism governing how the cells process
      the biophysical cues from these anisotropic geometries to their fate commitment
      is still poorly understood due to the limited availability of geometrical
      diversities (contact width above 50 nm) applicable to cell studies. Here, we
      firstly demonstrate that the biomolecular mechanism for enhanced neurogenesis on
      an anisotropic nanostructure is critically dependent on the resolution of a
      contact feature. We observed a totally different cellular response to anisotropic
      geometries by first utilizing a high-resolution nanogroove (HRN) structure with
      an extremely narrow contact width (15 nm). The width scale is sufficiently low to
      suppress the integrin clustering and enable us to elucidate how the contact area
      influences the neurogenesis of hNSCs at an aligned state. Both the HRN and
      control nanogroove (CN) pattern with a contact width of 1 MUm induced the
      spontaneous topographic alignment of hNSCs. However, intriguingly, the focal
      adhesion (FA) formation and cytoskeletal reorganization were substantially
      limited on the HRN, although the cells on the CN showed enhanced FA formation
      compared with flat surfaces. In particular, the hNSCs on the HRN surface
      exhibited a strikingly lower fraction of nuclear yes-associated protein (YAP)
      than on the CN surface, which was turned out to be regulated by Rho GTPase in the
      same way as the cells sense the mechanical properties of the environment.
      Considering the previously reported role of YAP on neurogenesis, our finding
      newly substantiates that YAP and Rho GTPase also can be transducers of hNSCs to
      process topographical alternation to fate decision. Furthermore, this study with
      the unprecedented high-resolution nanostructure suggests a novel geometry sensing
      model where the functional crosstalk between YAP signaling and Rho GTPase
      integrally regulate the fate commitment of the hNSCs.

PMID- 30207453
TI  - Adsorption of Plasma Proteins on Single-Walled Carbon Nanotubes Reduced
      Cytotoxicity and Modulated Neutrophil Activation.
AB  - Proteins in the bloodstream bind to carbon nanotubes (CNTs) through noncovalent
      interactions to form a protein corona, thereby effectively influencing the
      biological properties and blood biocompatibility of the CNTs. Here, we
      investigated the binding of common plasma proteins (i.e., human immunoglobulin G
      (IgG), human serum albumin (HSA), and fibrinogen (FG)) to carboxylated single
      walled CNTs (SWCNTs), and evaluated the effects of these different protein
      coronas on cytotoxicity to endothelial cells and immune response to neutrophils
      in the bloodstream. Measurements of adsorption parameters revealed tight binding
      of proteins to SWCNTs, and the SWCNTs adsorption capacities followed the order FG
      > HSA > IgG. In addition, the basic residues (Arg, Lys, His) were found to play
      an important role in the formation of protein-SWCNTs corona complexes and
      determine their adsorption capacity. Consistent with the higher protein
      adsorption capacity, FG more significantly reduced the cytotoxicity of CNTs to
      human umbilical vein endothelial cells than the other two proteins. However, only
      treatment of SWCNTs with IgG resulted in the enhancement of CNT-induced
      myeloperoxidase (MPO) release (i.e., neutrophil activation) in neutrophils, while
      MPO-dependent degradation of CNTs induced less cytotoxicity than initial
      nanomaterials. Consistent with these effects of protein coronas, the presence of
      serum attenuated the cytotoxicity of CNTs and CNTs could induce neutrophil
      activation in human blood plasma. Our study demonstrates the ability of adsorbed
      plasma proteins to influence cytotoxicity and neutrophil response caused by CNTs
      in the bloodstream.

PMID- 30207454
TI  - Probing the Growth Kinetics for the Formation of Uniform 1D Block Copolymer
      Nanoparticles by Living Crystallization-Driven Self-Assembly.
AB  - Living crystallization-driven self-assembly (CDSA) is a seeded growth method for
      crystallizable block copolymers (BCPs) and related amphiphiles in solution and
      has recently emerged as a highly promising and versatile route to uniform core
      shell nanoparticles (micelles) with control of dimensions and architecture.
      However, the factors that influence the rate of nanoparticle growth have not been
      systematically studied. Using transmission electron microscopy, small- and wide
      angle X-ray scattering, and super-resolution fluorescence microscopy techniques,
      we have investigated the kinetics of the seeded growth of
      poly(ferrocenyldimethylsilane)- b-(polydimethylsiloxane) (PFS- b-PDMS), as a
      model living CDSA system for those employing, for example, crystallizable
      emissive and biocompatible polymers. By altering various self-assembly parameters
      including concentration, temperature, solvent, and BCP composition our results
      have established that the time taken to prepare fiber-like micelles via the
      living CDSA method can be reduced by decreasing temperature, by employing
      solvents that are poorer for the crystallizable PFS core-forming block, and by
      increasing the length of the PFS core-forming block. These results are of general
      importance for the future optimization of a wide variety of living CDSA systems.
      Our studies also demonstrate that the growth kinetics for living CDSA do not
      exhibit the first-order dependence of growth rate on unimer concentration
      anticipated by analogy with living covalent polymerizations of molecular
      monomers. This difference may be caused by the combined influence of chain
      conformational effects of the BCP on addition to the seed termini and chain
      length dispersity.

PMID- 30207455
TI  - Fluorinated Carbon Nanotube/Nanofibrillated Cellulose Composite Film with
      Enhanced Toughness, Superior Thermal Conductivity, and Electrical Insulation.
AB  - Recently, graphene and carbon nanotubes (CNTs) promise considerable application
      potentials in the highly efficient thermal management of high-power devices
      because of their superb thermal conductivity (TC). However, the high electrical
      conductivity hampers their use in some fields where electrical insulating
      components are always required. Herein, to coordinate the thermal and electrical
      conductivity of CNT, fluorinated CNT (FCNT) was first used as a thermally
      conductive filler to prepare composite film with nanofibrillated celluloses
      (NFCs) via facile vacuum-assisted filtration. The obtained composite film shows a
      well-organized layered structure of the building blocks along the planar
      direction. Moreover, the one-dimensional structure of NFCs and the strong
      interaction of NFCs and FCNTs ensure sufficient connection between FCNT
      themselves and the reduced interfacial thermal resistance of NFCs/FCNTs, so that
      efficient heat transfer pathways can be well reserved, leading to simultaneous
      accessibility of high in-plane TC of 14.1 W m-1 K-1 and favorable electrical
      insulation property at an FCNT content of 35 wt %. Despite such a high FCNT
      loading, the strong interaction between NFCs and FCNTs enables the composite film
      to possess enhanced toughness, reliable mechanical strength, and flexibility.
      Therefore, we think that these outstanding comprehensive properties guarantee
      that the prepared composite film has promising applications in heat dissipation
      of next-generation portable and collapsible electronic devices.

PMID- 30207457
TI  - Multilayered Nanoplasmonic Arrays for Self-Referenced Biosensing.
AB  - Nanostructured sensors based on localized surface plasmon resonance (LSPR) offer
      a number of advantages over other optical sensing technologies, making them
      excellent candidates for miniaturized, label-free chemical and biological
      detection. Highly sensitive to local refractive index changes, the resonance
      peaks of the nanosensors shift by different amounts when subject to different
      biological and chemical environments. Modifications to the nanostructure surface
      allow for the detection of specific molecules and chemicals with shifts so
      sensitive that the presence of single molecules can be detected. However, this
      extreme sensitivity has its drawbacks. Resonance shifts also occur because of
      temperature shifts, light-intensity fluctuations, and other environmental
      factors. To distinguish detection from drift, a secondary sensor region is often
      required. This often doubles the size of the device, requires two light sources
      and detectors (or complex optics), doubles the sample volume required (which may
      be expensive, or may not be possible if the sample quantity is limited), and
      subjects the reference to potential biofouling. Here, we present a new proof-of
      concept multilayered LSPR sensor design that incorporates both a sensing layer
      and an encapsulated reference layer within the same region. By doing so, we are
      able to monitor and correct for sensor drift without the need for a secondary
      reference channel. We demonstrate the suitability of this sensor for sucrose
      concentration measurements and for the detection of biotin-avidin interactions,
      while also showing that the sensor can self-correct for drift. We believe that
      this multilayer sensor design holds promise for point-of-care diagnostics.

PMID- 30207456
TI  - Synergistic Effect of F- Doping and LiF Coating on Improving the High-Voltage
      Cycling Stability and Rate Capacity of LiNi0.5Co0.2Mn0.3O2 Cathode Materials for
      Lithium-Ion Batteries.
AB  - A commercial LiNi0.5Co0.2Mn0.3O2 (LNCM) cathode material is purposefully modified
      using a small account of LiPF6 as one precursor via a simple means at low
      calcination temperature in air. X-ray diffraction, scanning electron microscopy,
      and transmission electron microscopy images reveal that this modification process
      keeps the layered bulk structure of LNCM even though the surface components have
      obviously been modified. Electron energy loss spectroscopy and X-ray
      photoelectron spectroscopy with different etching depths further prove the
      formation of LiF and F- doping on the LNCM surface, which simultaneously triggers
      partial Ni3+ reduction to Ni2+; and the metal-oxygen bond is partially replaced
      by a higher energy metal-fluorine bond. The modified material (LNCM-2) retains
      93.7% of its initial capacity and delivers 179.4 mAh g-1 at a current density of
      0.5 C after 100 stable cycles at 3.0-4.5 V. Meanwhile, LNCM-2 is able to maintain
      capacity retention up to 81.1% after 300 cycles at 5 C, much better than the
      original LNCM (35.1%) in the commercial electrolyte. Remarkably, 90% of initial
      capacity is retained for LNCM-2 with considerably improved Coulombic efficiency
      (>99.5%) at 5 C after 300 cycles within a voltage range of 3-4.5 V compared with
      the primary LNCM using succinonitrile-based electrolyte. Consequently, these
      results fully demonstrate the advantages of synergistic effect between F- doping
      and LiF coating.

PMID- 30207458
TI  - Bridging the Gap between Reality and Ideal in Chemical Vapor Deposition Growth of
      Graphene.
AB  - Graphene, in its ideal form, is a two-dimensional (2D) material consisting of a
      single layer of carbon atoms arranged in a hexagonal lattice. The richness in
      morphological, physical, mechanical, and optical properties of ideal graphene has
      stimulated enormous scientific and industrial interest, since its first
      exfoliation in 2004. In turn, the production of graphene in a reliable,
      controllable, and scalable manner has become significantly important to bring us
      closer to practical applications of graphene. To this end, chemical vapor
      deposition (CVD) offers tantalizing opportunities for the synthesis of large
      area, uniform, and high-quality graphene films. However, quite different from the
      ideal 2D structure of graphene, in reality, the currently available CVD-grown
      graphene films are still suffering from intrinsic defective grain boundaries,
      surface contaminations, and wrinkles, together with low growth rate and the
      requirement of inevitable transfer. Clearly, a gap still exits between the
      reality of CVD-derived graphene, especially in industrial production, and ideal
      graphene with outstanding properties. This Review will emphasize the recent
      advances and strategies in CVD production of graphene for settling these issues
      to bridge the giant gap. We begin with brief background information about the
      synthesis of nanoscale carbon allotropes, followed by the discussion of
      fundamental growth mechanism and kinetics of CVD growth of graphene. We then
      discuss the strategies for perfecting the quality of CVD-derived graphene with
      regard to domain size, cleanness, flatness, growth rate, scalability, and direct
      growth of graphene on functional substrate. Finally, a perspective on future
      development in the research relevant to scalable growth of high-quality graphene
      is presented.

PMID- 30207459
TI  - Adsorption of Methylmercury onto Geobacter bemidijensis Bem.
AB  - The anaerobic bacterium Geobacter bemidijensis Bem has the unique ability to both
      produce and degrade methylmercury (MeHg). While the adsorption of MeHg onto
      bacterial surfaces can affect the release of MeHg into aquatic environments as
      well as the uptake of MeHg for demethylation, the binding of MeHg to the
      bacterial envelope remains poorly understood. In this study, we quantified the
      adsorption of MeHg onto G. bemidijensis and applied X-ray absorption spectroscopy
      (XAS) to elucidate the mechanism of MeHg binding. The results showed MeHg
      adsorption onto G. bemidijensis cell surfaces was rapid and occurred via
      complexation to sulfhydryl functional groups. Titration experiments yielded cell
      surface sulfhydryl concentrations of 3.8 +/- 0.2 MUmol/g (wet cells). A one-site
      adsorption model with MeHg binding onto sulfhydryl sites provided excellent fits
      to adsorption isotherms conducted at different cell densities. The log K binding
      constant of MeHg onto the sulfhydryl sites was determined to be 10.5 +/- 0.4.
      These findings provide a quantitative framework to describe MeHg binding onto
      bacterial cell surfaces and elucidate the importance of bacterial cells as
      possible carriers of adsorbed MeHg in natural aquatic systems.

PMID- 30207460
TI  - Degradation of PFOA Substitute: GenX (HFPO-DA Ammonium Salt): Oxidation with
      UV/Persulfate or Reduction with UV/Sulfite?
AB  - Hexafluoropropylene oxide dimer acid (HFPO-DA, ammonium salt with trade name:
      GenX) has been recently detected in river water worldwide. There are significant
      concerns about its persistence, and potential adverse effects to the biota. In
      this study, the degradability of GenX by typical advanced redox technologies
      (UV/persulfate and UV/sulfate) is investigated. Results demonstrate that <5% GenX
      is oxidized after 3 h in UV/persulfate system, which is much lower than ~27% for
      PFOA. In comparison, GenX can be readily degraded and defluorinated by hydrated
      electron (eaq-) generated by UV/sulfite system. Specifically, GenX is not
      detectable after 2 h, and >90% of fluoride ion is recovered 6 h later. This is
      attributed to the accumulation and subsequent degradation of CF3CF2COOH and
      CF3COOH, which are stable intermediates of GenX degradation. Mechanistic
      investigations suggest that the etheric bond in the molecule is a favorable
      attack point for the eaq-. Such finding is corroborated by quantum chemical
      calculations. The side CF3- at the alpha-carbon probably acts as an effective
      barrier that prevents GenX from being cleaved by SO4-* or OH* at its most
      sensible point (i.e. the carboxyl group). This study illustrates that reduction
      by UV/sulfite might be a promising technology to remove GenX from contaminated
      water.

PMID- 30207461
TI  - Elucidating the Formation and Transformation Mechanisms of the Switchable Metal
      Organic Framework ELM-11 by Powder and Single-Crystal EPR Study.
AB  - The effect of the synthesis conditions on the structure and guest-responsive
      properties of a "gate pressure" metal-organic framework (MOF) with composition
      [Cu(4,4'-bipy)2(BF4)2] n (4,4'-bipy = 4,4'-bipyridine), also known as ELM-11 (ELM
      = elastic layer material) was investigated. Two different batches of ELM-11,
      synthesized from water-methanol and water-acetonitrile solutions, have been
      entirely characterized by PXRD, nitrogen (77 K) and carbon dioxide (195 K)
      physisorption, elemental analysis, DRIFT, TG, and SEM. Both ELM-11 samples were
      studied by electron paramagnetic resonance (EPR) spectroscopy in order to follow
      the change in the local structure of the copper ion during the activation and
      resolvation. Continuous wave X-band EPR measurements on powder samples provided
      an elongated octahedral coordination symmetry of the cupric ions and revealed
      different axial ligands in the as-synthesized and activated forms in both bulk
      samples of ELM-11. One of the procedures was amended in order to slow down the
      crystallization that allows isolation of single crystals of two polymorphic
      modifications of Cu-4,4'-bipyridine coordination polymers, namely [Cu(4,4'
      bipy)2(CH3CN)2](BF4)2 and [Cu2O(4,4'-bipy)3(CH3CN)4](BF4)2, one of which shows a
      crystal structure similar to that of ELM-11. Further single-crystal EPR
      experiments on the as-synthesized material [Cu(4,4'-bipy)2(CH3CN)2](BF4)2
      revealed the orientation of the g tensor of the cupric ions and proved that
      layers of acetonitrile-synthesized ELM-11 are arranged perpendicularly to the
      crystallographic c axis.

PMID- 30207462
TI  - Relationship between the Crystal Structure and Electrical Properties of Oxide Ion
      Conducting Ba3W1.2Nb0.8O8.6.
AB  - The oxide ionic conductor Ba3W1.2Nb0.8O8.6 has been synthesized as part of an
      investigation into the new class of Ba3M'M''O8.5 (M' = W, Mo; M'' = Nb) oxide-ion
      conducting hexagonal perovskite derivatives. The substitution of W6+ for Nb5+ in
      Ba3W1+ xNb1- xO8.5+ x/2 leads to an increase in the oxygen content, which
      enhances the low-temperature ionic conductivity. However, at 400  degrees C, the
      ionic conductivity of Ba3W1.2Nb0.8O8.6 is still significantly lower than the
      molybdenum compound Ba3MoNbO8.5. Remarkably, at 600  degrees C the bulk oxide
      ionic conductivities of Ba3MoNbO8.5, Ba3WNbO8.5, and Ba3W1.2Nb0.8O8.6 are very
      similar (sigmab = 0.0022, 0.0017, and 0.0016 S cm-1, respectively). The variable
      temperature neutron diffraction results reported here demonstrate that
      Ba3W1.2Nb0.8O8.6 undergoes a similar structural rearrangement to Ba3MoNbO8.5
      above 300  degrees C, but the ratio of (W/Nb)O4 tetrahedra to (W/Nb)O6 octahedra
      rises at a faster rate upon heating between 300 and 600  degrees C. There is a
      clear relationship between the ionic conductivity of Ba3M'1+ xM''1- xO8.5+ x/2
      (M' = W, Mo; M'' = Nb) phases and the number of tetrahedrally coordinated M' and
      M " cations present within the crystal structure.

PMID- 30207463
TI  - Atomic Ordering of Two Neighboring Transition Metals-Cu and Zn from Binary CuZn
      to Ternary Cu3ZnSb.
AB  - A new ternary compound Cu3ZnSb was synthesized by high temperature solid state
      synthesis and characterized by single crystal X-ray diffraction and energy
      dispersive X-ray analysis. The ternary Cu3ZnSb crystallizes in the tetragonal
      crystal system with the space group P4/ nmm (129), and its unit cell contains 10
      atoms which are distributed over 4 independent crystallographic positions. The
      structure is built up with [Cu3Sb] slabs that correspond to the unit cells of
      Cu2Sb and planar 44 nets of Zn atoms. The planar nets of Zn atoms are
      interspersed between two adjacent [Cu3Sb] slabs. The structure can be viewed as
      alternating units of Cu2Sb and CsCl type beta'-brass (CuZn) structures in the
      [001]. An unusual atomic ordering of two neighboring transition metals Cu and Zn
      is observed and is confirmed by first principle calculations. The atomic ordering
      of Cu and Zn is retained from binary beta'-brass structure (CuZn) to ternary
      Cu3ZnSb. Total energy calculations confirmed the experimental model of Cu/Zn
      ordering to be the most stable in the structure of Cu3ZnSb. The calculated
      density of states (DOS) and crystal orbital Hamiltonian population (COHP) explain
      the stability and bonding characteristics in the structure of Cu3ZnSb. The
      implication of the persistent Cu/Zn ordering in ternary phases for materials
      design is emphasized.

PMID- 30207464
TI  - Allosteric Activation of Striatal-Enriched Protein Tyrosine Phosphatase (STEP,
      PTPN5) by a Fragment-like Molecule.
AB  - Protein tyrosine phosphatase non-receptor type 5 (PTPN5, STEP) is a brain
      specific phosphatase that regulates synaptic function and plasticity by
      modulation of N-methyl-d-aspartate receptor (NMDAR) and alpha-amino-3-hydroxy-5
      methyl-4-isoxazolepropionic acid receptor (AMPAR) trafficking. Dysregulation of
      STEP has been linked to neurodegenerative and neuropsychiatric diseases,
      highlighting this enzyme as an attractive therapeutic target for drug discovery.
      Selective targeting of STEP with small molecules has been hampered by high
      conservation of the active site among protein tyrosine phosphatases. We report
      the discovery of the first small molecule allosteric activator for STEP that
      binds to the phosphatase domain. Allosteric binding is confirmed by both X-ray
      and 15N NMR experiments, and specificity has been demonstrated by an enzymatic
      test cascade. Molecular dynamics simulations indicate stimulation of enzymatic
      activity by a long-range allosteric mechanism. To allow the scientific community
      to make use of this tool, we offer to provide the compound in the course of an
      open innovation initiative.

PMID- 30207465
TI  - BACE1 Inhibitory Meroterpenoids from Aspergillus terreus.
AB  - Sixteen 3,5-dimethylorsellinic acid-based (DMOA-based) meroterpenoids, including
      10 new compounds, asperterpenes D-M (1-10), were obtained from Aspergillus
      terreus. The structures and absolute configurations of the new compounds were
      confirmed by extensive spectroscopy, single-crystal X-ray diffraction analysis,
      and experimental electronic circular dichroism (ECD) measurements. Compounds 2,
      3, and 7 are the first 3,5-dimethylorsellinic acid-based meroterpenoids
      possessing a unique cis-fused A/B ring system. These new compounds were evaluated
      for their inhibitory activity against beta-site amyloid precursor protein
      cleaving enzyme 1 (BACE1). Compounds 2, 3, and 7, the first 3,5
      dimethylorsellinic acid-based meroterpenoids possessing cis-fused A/B rings,
      exhibited significant inhibitory activities against BACE1 with IC50 values of
      3.3, 5.9, and 31.7 MUM, respectively.

PMID- 30207466
TI  - Effects of Ancillary Ligands on Redox and Chemical Properties of Ruthenium
      Coordinated Azoaromatic Pincer.
AB  - In this work, the effect of the electronically different ancillary ligands on the
      overall properties of the RuIIL moiety (L = 2,6-bis(phenylazo)pyridine) in
      heteroleptic complexes of general formula [RuLQCl]0/+ was investigated. Four
      different ancillary ligands (Q) with different electronic effects were used to
      prepare the heteroleptic compounds from the precursor complex, [RuL(CH3CN)Cl2]
      (1); Q = pcp: 2-(4-chloro-phenylazo)pyridine (strong pi-acceptor), [2]+; bpy:
      2,2'-bipyridyl (moderate pi-acceptor), [3]+; acac-: acetylacetonate (strong sigma
      donor), 4; and DTBCat2-: 3,5-di- tert-butyl catecholate (strong pi-donor), 5. The
      complexes [2]+, [3]+, 4, and 5 were fully characterized and structurally
      identified. The electronic structures of these complexes along with their redox
      partners were elucidated by using a host of physical measurements: nuclear
      magnetic resonance, cyclic voltammetry, electronic paramagnetic resonance, UV-vis
      NIR spectroscopy, and density functional theory. The studies revealed significant
      effects of the coligands on azo bond lengths of the RuL moiety and their redox
      behavior. Aerobic alcohol oxidation reactions using these Ru complexes as
      catalysts were scrutinized. It was found that the catalytic efficiency is
      primarily controlled by the electronic effect of the coligand. Accordingly, the
      complex [2]+ (containing a strong pi-acceptor coligand, pcp) brings about
      oxidation efficiently, producing 86% of benzaldehyde. In comparison, however, the
      complexes 4 and 5 (containing electron donating coligand) furnished only 15-20%
      of benzaldehyde under identical reaction conditions. Investigations of the
      reaction mechanism suggest that an unstable Ru-H species is formed, which is
      transformed to a Ru-hydrazo intermediate by H-walking as reported by Hall et al.
      ( J. Am. Chem. Soc., 2015, 137, 12330). Aerial O2 regenerates the catalyst via
      oxidation of the hydrazo intermediate.

PMID- 30207467
TI  - Identification of Key Residues Associated with the Interaction between Plutella
      xylostella Sigma-Class Glutathione S-Transferase and the Inhibitor S-Hexyl
      Glutathione.
AB  - Glutathione S-transferases (GSTs) are important detoxification enzymes involved
      in the development of metabolic resistance in Plutella xylostella. Uncovering the
      interactions between representative PxGSTs and the inhibitor S-hexyl glutathione
      (GTX), helps in the development of effective PxGST inhibitors for resistance
      management. As the PxGST most severely inhibited by GTX, PxGSTsigma (sigma-class
      PxGST) adopts the canonical fold of insect GSTs. The formation of the PxGSTsigma
      GTX complex is mainly driven by H-bond and hydrophobic interactions derived from
      the side chains of favorable residues. Of the residues composing the active site
      of PxGSTsigma, Lys43 and Arg99 are two hot spots, first reported in the binding
      of GSH derivatives to GSTs. Such differences indicate the metabolism
      discrimination of different insect GSTs. Unfavorable interactions between the
      PxGSTsigma active site and GTX are depicted as well. The research guides the
      discovery and optimization of PxGSTsigma inhibitors.

PMID- 30207468
TI  - A Thiourea Tether in the Second Coordination Sphere as a Binding Site for CO2 and
      a Proton Donor Promotes the Electrochemical Reduction of CO2 to CO Catalyzed by a
      Rhenium Bipyridine-Type Complex.
AB  - The electrochemical reduction of CO2 has been extensively investigated in recent
      years, with the expectation that a detailed mechanistic understanding could
      achieve the goal of finding a stable catalyst with high turnover frequencies and
      low reduction potentials. In the catalytic cycle of the carbon dioxide
      hydrogenase enzyme, it has been suggested that the reduced metal center reacts
      with CO2 to form a carboxylate intermediate that is stabilized by hydrogen
      bonding using a histidine moiety in the second coordination sphere. Using the
      well-known fac-Re(I)bipyridine(CO)3Cl complex as a starting point, the bipyridine
      ligand was modified in the second coordination sphere with a thiourea tether that
      is known to form hydrogen bonds with carbonyl moieties. The resulting Re(I)
      catalyst was an excellent electrocatalyst for the selective reduction of CO2 to
      CO, with a turnover frequency of 3040 s-1. The binding of CO2 to the thiourea
      tether was observable by 1H NMR, and NOE experiments showed that the hydrogen
      atoms of the thiourea group were labile. Further experiments indicated that the
      thiourea moiety is also a local proton source and addition of an external proton
      source actually inhibits catalysis. The absence of a kinetic isotope effect was
      explained through DFT calculations that showed that the proton invariably jumps
      to the nearest CO2 oxygen atom to form a metal-carboxylic acid without going
      through any minimum or transition state. EPR and NMR spectroscopies were used to
      identify the various reduced intermediates. Thus, the thiourea tether in the
      second coordination sphere can bind CO2, stabilize carboxylic acid reaction
      intermediates, and directly act as a local proton source, leading to a
      significantly more active catalyst.

PMID- 30207469
TI  - One-Dimensional Thiocyanato-Bridged Fe(II) Spin Crossover Cooperative Polymer
      With Unusual FeN5S Coordination Sphere.
AB  - We present here a novel example of spin crossover phenomenon on a Fe(II) one
      dimensional chain with unusual N5S coordination sphere. The [{Fe(tpc-OMe)(NCS)(MU
      NCS)} n] (1) compound was prepared using the tridentate tpc-OMe ligand (tpc-OMe =
      tris(2-pyridyl)methoxymethane), FeCl2.4H2O, and the KSCN salt. Crystallographic
      investigations revealed that the Fe(II) ions are connected by a single bridging
      NCS- ligand (MU-kappaN:kappaS-SCN coordination mode) to afford a zigzag neutral
      chain running along the [010] direction, in which the thiocyanato bridging groups
      adopt a cis head-to-tail configuration. The (N5S) metal environment arises from
      one thiocyanato-kappaS and two thiocyanato-kappaN ligands and from three pyridine
      of the fac-tpc-OMe tripodal ligand. This compound presents a unique extension of
      Fe(II) binuclear complexes into linear chains built on similar tripodal ligands
      and bridging thiocyanate anions. Compound 1 shows a spin crossover (SCO) behavior
      which has been evidenced by magnetic, calorimetric, and structural
      investigations, revealing a sharp cooperative spin transition with a transition
      temperature of ca. 199 K. Temperature scan rate studies revealed a very narrow
      hysteresis loop (~1 K wide). Photoswitching of this compound was also performed,
      evidencing a very fast relaxation process at low temperature. Among other
      factors, the linearity of the N-bound terminal thiocyanato ligand appears as the
      main structural characteristic at the origin of the presence of the SCO
      transition in compound 1 and in the two others Fe(II) previous systems involving
      thiocyanato-bridges and tripodal tris(2-pyridyl)methane ligands.

PMID- 30207470
TI  - Sulfonic Acid-Containing Flavonoids from the Roots of Phyllanthus acidus.
AB  - Six new sulfonic acid-containing flavonoids, acidoflavanone (1), acidoauronol
      (2), 5- O-methylacidoauronol (3), acidoaurone (4), acidoisoflavone (5), and
      acidoflavonol (6), were isolated from the EtOH extract of the roots of
      Phyllanthus acidus. Their structures were unambiguously established by
      interpretation of their HRESIMS and 1D and 2D NMR data, single-crystal X-ray
      diffraction analysis, and comparison to the literature data. These new structures
      represent the first examples of sulfonic acid-containing flavanones, auronols,
      aurones, and isoflavones.

PMID- 30207471
TI  - Formation of Water Molecule Bridges Governs Water Sorption Mechanisms in Soil
      Organic Matter.
AB  - Adsorption is the main mechanism of capturing water in soil organic matter (SOM)
      under arid conditions. This process is governed by hydrophilic sites, which are
      gradually bridged via water molecule bridges (WaMB). Until now, the link between
      WaMB and other types of water molecules occurring in SOM during sorption has not
      been systematically investigated. In this work, we compared the formation and
      stability of WaMB simultaneously with the total water content, strength of water
      binding, and kinetics of water sorption in a vacuum-dried model SOM (sapric
      histosol) exposed to different relative water pressures. The same parameters were
      then determined in SOM exposed to reduced relative pressures. The adsorption
      resulted in an adsorption isotherm with a Langmuir-like part below a relative
      pressure of 0.5 and a Brunauer-Emmett-Teller-like isotherm at higher relative
      pressures. The WaMB formation was observed at a relative pressure of 0.32, which
      represented the pressure at which Langmuir-like part reached a plateau. The
      binding energy showed a linear decrease with an increasing pressure; the slope
      increased at a relative pressure of 0.46. Reduction of relative pressures above
      0.46 showed that the water content remained constant, but the binding energy was
      lowered. In contrast, below a relative pressure of 0.46, the water content
      decreased, but the binding energy was not changed. The results indicate that in
      SOM exposed to different relative pressures, water exists in three types: first,
      it is strongly bound to primary sorption sites (Langmuir-like), second, it occurs
      in the form of WaMB water, which bridges functional groups and where predominates
      water-water interactions, and third, it occurs in the form of phase water, which
      is located in larger pores similar to the pure water phase. The latter either
      surrounds the WaMB and destabilizes it or, for higher water content, links
      individual WaMB and successively reduces their stabilizing effect. Formation of
      phase water leads to swelling processes including plasticizing effects and
      potential volume changes of SOM. Accordingly, the results suggest that at lower
      water relative pressures WaMB stabilizes the SOM structure, whereas at higher
      water relative pressures, it influences the formation of phase water and thereby
      the total water content in SOM.

PMID- 30207472
TI  - A Protocol To Transform Sulfones into Nitrones and Aldehydes.
AB  - A simple method to transform sulfones into nitrones and therefore into the
      corresponding carbonyl derivatives has been developed. Some examples demonstrate
      that it is a new reliable and versatile reaction in the toolbox of sulfones that
      has great synthetic potential. NMR and computational studies were used to
      elucidate the mechanism.

PMID- 30207473
TI  - Leutusome: A Biomimetic Nanoplatform Integrating Plasma Membrane Components of
      Leukocytes and Tumor Cells for Remarkably Enhanced Solid Tumor Homing.
AB  - Cell membrane-camouflaged nanoparticles have appeared as a promising platform to
      develop active tumor targeting nanomedicines. To evade the immune surveillance,
      we designed a composite cell membrane-camouflaged biomimetic nanoplatform,
      namely, leutusome, which is made of liposomal nanoparticles incorporating plasma
      membrane components derived from both leukocytes (murine J774A.1 cells) and tumor
      cells (head and neck tumor cells HN12). Exogenous phospholipids were used as
      building blocks to fuse with two cell membranes to form liposomal nanoparticles.
      Liposomal nanoparticles made of exogenous phospholipids only or in combination
      with one type of cell membrane were fabricated and compared. The anticancer drug
      paclitaxel (PTX) was used to make drug-encapsulating liposomal nanoparticles.
      Leutusome resembling characteristic plasma membrane components of the two cell
      membranes were examined and confirmed in vitro. A xenograft mouse model of head
      and neck cancer was used to profile the blood clearance kinetics,
      biodistribution, and antitumor efficacy of the different liposomal nanoparticles.
      The results demonstrated that leutusome obtained prolonged blood circulation and
      was most efficient accumulating at the tumor site (79.1 +/- 6.6% ID per gram of
      tumor). Similarly, leutusome composed of membrane fractions of B16 melanoma cells
      and leukocytes (J774A.1) showed prominent accumulation within the B16 tumor,
      suggesting the generalization of the approach. Furthermore, PTX-encapsulating
      leutusome was found to most potently inhibit tumor growth while not causing
      systemic adverse effects.

PMID- 30207474
TI  - A Cyclopropenethione-Phosphine Ligation for Rapid Biomolecule Labeling.
AB  - Cyclopropenethiones are reported as new bioorthogonal reagents. These motifs
      react readily with substituted phosphines to provide thiocarbonyl adducts. In
      some cases, the ligations are >300-fold faster than analogous reactions with
      bioorthogonal cyclopropenones. Dialkyl cyclopropenethiones are also stable in
      aqueous buffers and can be used for biomolecule labeling in vitro and in cell
      lysate. The rapid reactivity and biocompatibility of cyclopropenethiones suggest
      that they will be useful probes for cellular studies.

PMID- 30207475
TI  - Omniphobic Metal Surfaces with Low Contact Angle Hysteresis and Tilt Angles.
AB  - Various metal (Al, Ti, Fe, Ni, and Cu) surfaces with native oxide layers were
      rendered "omniphobic" by a simple thermal treatment of neat liquid
      trimethylsiloxy-terminated polymethylhydrosiloxanes (PMHSs) with a range of
      different molecular weights (MWs). Because of this treatment, the PMHS chains
      were covalently attached to the oxidized metal surfaces, giving 2-10 nm thick
      PMHS layers. The resulting surfaces were fairly smooth, liquid-like, and showed
      excellent dynamic omniphobicity with both low contact angle hysteresis (?5
      degrees ) and substrate tilt angles (?8 degrees ) toward small-volume liquid
      drops (5 MUL) with surface tensions ranging from 20.5 to 72.8 mN/m. Droplet
      mobility was improved overall as a result of heating the substrates to 70 
      degrees C. The reaction kinetics and final dynamic dewetting properties were
      found to be not dependent of the types of metals employed or MWs of PMHS, but
      mainly dominated by both reaction temperatures and reaction times.

PMID- 30207476
TI  - Discovery and Validation of Potential Serum Biomarkers for Pediatric Patients
      with Congenital Heart Diseases by Metabolomics.
AB  - To identify and screen serum biomarkers to determine pediatric patients with
      congenital heart diseases (PCH) from healthy control children (NC), a total of
      614 clinically diagnosed subjects from three hospitals, including 491 PCH and 234
      NC, were enrolled for nontargeted proton nuclear magnetic resonance spectroscopy
      (1H NMR)-based and targeted ultra-high-performance liquid chromatography-tandem
      mass spectroscopy (UPLC-MS/MS)-based metabolomics studies. Nineteen serum
      metabolites distinguishing PCH from NC were identified by 1H NMR-based
      metabolomic analysis. The amino acid and choline metabolic pathways were
      considered to be closely related to PCH. The serum levels of 13 metabolites in
      these two pathways were further determined by UPLC-MS/MS and observed to be
      altered significantly in PCH. Taurine, glutamine, and glutamate presented
      considerable diagnostic value for the diagnosis of PCH (AUROC > 0.80). Logistic
      regression analysis showed that a combination of four variables, namely, betaine,
      taurine, glutamine, and phenylalanine, yields a high diagnostic value (AUROC =
      0.949) and prediction accuracy (89.1%) for differentiating PCH from the NC, and
      the sensitivity and specificity were 93.9 and 95.2%, respectively. Further double
      blind sample prediction showed that the accuracy of the model was 83.8% for 80
      unknown samples. Our results showed that the serum amino acid and choline
      metabolite levels in PCH were changed considerably. The combination of four
      metabolites, namely, betaine, taurine, glutamine, and phenylalanine, can be used
      as potential serum biomarkers in PCH diagnosis, which contributes to the early
      PCH screening.

PMID- 30207477
TI  - Expediently Scalable Synthesis and Antifungal Exploration of (+)-Yahazunol and
      Related Meroterpenoids.
AB  - The efficient synthesis and antifungal exploration of (+)-yahazunol and related
      natural products are described. Central to this strategy is the Barton
      decarboxylative coupling, comprising a one-pot radical decarboxylation and
      quinone addition cascade. The scalable synthesis of (+)-yahazunol was
      accomplished in five longest linear sequences (LLS) starting from commercially
      available and inexpensive (-)-sclareol. The divergent translational potential of
      (+)-yahazunol was demonstrated by the expedient preparation of (-)-zonarone, (-)
      isozonarone, (-)-zonarol, (-)-isozonarol, (+)-chromazonarol, and (+)-yahazunone.
      This approach also enables the formal synthesis of puupehenol, puupehedione, and
      hongoquercin A. Antifungal evaluation was performed, and this represents the
      first biological profiles for (+)-yahazunone, (+)-8- O-acetylyahazunone, and (+)
      8- O-acetylyahazunol. (+)-Chromazonarol and (+)-yahazunone are promising
      candidates against Sclerotinia scleotiorum, with EC50 values of 24.1 and 28.7
      MUM, respectively, demonstrating advantages over the original model (DM) and
      synthesized heterocyclic mimic (3a) of meroterpenoids. This will favor the
      establishment of a chemical repertoire in the management of different plant
      diseases.

PMID- 30207478
TI  - Cp*Co(III)-Catalyzed C-H Acylmethylation of Arenes by Employing Sulfoxonium
      Ylides as Carbene Precursors.
AB  - A Cp*Co(III)-catalyzed C-H bond functionalization of a range of arenes by
      employing sulfoxonium ylides as carbene precursors instead of diazo compounds and
      other carbene precursors has been established. This reaction is highly efficient
      without any additive, possesses high step and atom economies, and tolerates a
      range of functional groups.

PMID- 30207479
TI  - As-Heteropentacenes: An Experimental and Computational Study on a Novel Class of
      Heteroacenes.
AB  - Arsenic-containing heteropentacenes were synthesized for the first time;
      bibenzofuran, benzothienyl benzofuran, and bibenzothiophene were bridged by
      arsenic atoms. Their structures and properties were experimentally and
      computationally studied using X-ray crystallography, optical and electronic
      properties, aromaticity, charge carrier mobility, etc. The present findings on
      the novel class of heteroacenes will expand functional organic chemistry.

PMID- 30207480
TI  - Nickel-Catalyzed Highly Enantioselective Hydrogenation of beta-Acetylamino
      Vinylsulfones: Access to Chiral beta-Amido Sulfones.
AB  - The nickel/( S)-Binapine complex was found to be an efficient catalyst for
      asymmetric hydrogenation of beta-acetylamino vinylsulfones to afford chiral beta
      Amido sulfones with excellent yields and enantioselectivities (up to 95% yields
      and >99% ee). This protocol has good compatibility with a series of substituted (
      Z)-beta-acetylamino vinylsulfones or Z/ E isomeric mixtures. A gram-scale
      reaction has also been achieved in the presence of a 0.2 mol % catalyst loading.

PMID- 30207481
TI  - Hyperdioxane A, a Conjugate of Dibenzo-1,4-dioxane and Sesquiterpene from
      Hypericum ascyron.
AB  - Two new dibenzo-1,4-dioxane derivatives, hyperdioxanes A (1) and B (2), were
      isolated from the roots of a Hypericaceous plant, Hypericum ascyron. Hyperdioxane
      A (1) is a conjugate of dibenzo-1,4-dioxane and sesquiterpene with an
      unprecedented heptacyclic ring system. The structures of 1 and 2 were assigned by
      detailed spectroscopic analyses, including application of a modified Mosher's
      method. A possible biogenetic pathway of hyperdioxane A (1) from hyperdioxane B
      (2) and a sesquiterpene, eremophil-9,11(13)-dien-8beta,12-olide (3), is
      presented.

PMID- 30207482
TI  - Abstracts and Case Studies From the College of American Pathologists 2018 Annual
      Meeting (CAP18).
AB  - and case study poster sessions will be conducted during the 2018 College of
      American Pathologists Annual Meeting (CAP18), which is scheduled for October 20
      to 24, 2018. The meeting will take place at the Hyatt Regency, Chicago, Illinois.
      The poster sessions will occur in the CAP18 Exhibit Hall. Specific dates and
      times for each poster session are listed below; "poster focus" times are
      dedicated poster viewing periods. Also shown before each poster session are the
      subject areas that will be presented.

PMID- 30207483
TI  - Abstract/Case Study Review Committee for the College of American Pathologists
      2018 Annual Meeting (CAP18).

PMID- 30207484
TI  - Causes and prevention of postoperative myocardial injury.
AB  - Over the past few years non-cardiac surgery has been recognised as a serious
      circulatory stress test which may trigger cardiovascular events such as
      myocardial infarction, in particular in patients at high risk. Detection of these
      postoperative cardiovascular events is difficult as clinical symptoms often go
      unnoticed. To improve detection, guidelines advise to perform routine
      postoperative assessment of cardiac troponin. Troponin elevation - or
      postoperative myocardial injury - can be caused by myocardial infarction.
      However, also non-coronary causes, such as cardiac arrhythmias, sepsis and
      pulmonary embolism, may play a role in a considerable number of patients with
      postoperative myocardial injury. It is crucial to acquire more knowledge about
      the underlying mechanisms of postoperative myocardial injury because effective
      prevention and treatment options are lacking. Preoperative administration of beta
      blockers, aspirin, statins, clonidine, angiotensin-converting enzyme inhibitors
      and angiotensin receptor blockers, and preoperative revascularisation have all
      been investigated as preventive options. Of these, only statins should be
      considered as the initiation or reload of statins may reduce the risk of
      postoperative myocardial injury. There is also not enough evidence for
      intraoperative measures such blood pressure optimisation or intensified medical
      therapy once patients have developed postoperative myocardial injury. Given the
      impact, better preoperative identification of patients at risk of postoperative
      myocardial injury, for example using preoperatively measured biomarkers, would be
      helpful to improve cardiac optimisation.

PMID- 30207485
TI  - It Does Take Two to Tango: An Applied Conversation Analysis of Interactions
      between a Psychiatrist and Service-Users Discussing Medication.
AB  - Decisions concerning psychiatric medication are complex and often involve a
      protracted process of trial and error. We examine three recorded meetings for
      power-sharing and power-taking discourse strategies employed by both the
      psychiatrist and mental health service-user, when discussing psychiatric
      medication. We identify examples of good practice, as well as missed
      opportunities to engage service-users in co-constructed dialogue, and highlight
      that participation and active involvement in decisions is not best seen as a
      fixed pattern, but is a complex interplay that changes both between and within
      interactions.

PMID- 30207486
TI  - The longevity of casein phosphopeptide-amorphous calcium phosphate fluoride
      varnish's preventative effects: Assessment of white spot lesion formation.
AB  - OBJECTIVES: To test how long casein phosphopeptide-amorphous calcium phosphate
      (CPP-ACP) fluoride varnish prevents enamel demineralization in vitro. MATERIALS
      AND METHODS: Human molars and premolars were sectioned buccolingually and
      randomly assigned to two groups. Standardized pretreatment images of enamel
      surfaces were obtained using FluoreCam. The control group received no treatment,
      and the experimental group received an application of CPP-ACP fluoride varnish.
      Over simulated periods of 2, 4, 8, and 12 weeks, specimens were placed in a
      toothbrushing simulator, thermocycled, subjected to 9 days of pH cycling, and
      imaged with FluoreCam. Samples were sectioned and polished for polarized light
      microscope (PLM) evaluation. RESULTS: There were statistically significant time (
      P < .001) and varnish ( P < .001) effects on area, intensity, and impact of
      enamel demineralization. The control group showed significant and progressive
      demineralization over the 12 weeks ( P < .001). The experimental group revealed
      no significant demineralization during the first 4 weeks ( P > .05) and
      significant ( P < .001) increases thereafter. Experimental demineralization after
      12 weeks was comparable to 2-week demineralization in the controls, with
      significant between-group differences ( P < .001) in enamel demineralization at
      all time points. PLM of the control and experimental groups revealed lesion
      depths of 90 +/- 34 MUm and 37 +/- 9 MUm, respectively. CONCLUSIONS: Within the
      limitations of this in vitro study, CPP-ACP fluoride varnish prevents enamel
      demineralization for at least 4 weeks and limits demineralization up to 12 weeks.

PMID- 30207487
TI  - The National Dental Practice-Based Research Network adult anterior open bite
      study: A description of the practitioners and patients.
AB  - OBJECTIVES:: To describe the demographic and practice characteristics of the
      clinicians enrolled in a large, prospective cohort study examining
      recommendations and treatment for adult anterior open bite (AOB) and the
      relationship between these characteristics and practitioners' self-reported
      treatment preferences. The characteristics of the AOB patients recruited were
      also described. MATERIALS AND METHODS:: Practitioners were recruited from the
      National Dental Practice-Based Research Network. Participants in the study
      consisted of practitioners and their adult AOB patients in active treatment. Upon
      enrollment, practitioners completed questionnaires enquiring about demographics,
      treatment preferences for adult AOB patients, and treatment recommendations for
      each patient. Patients completed questionnaires on demographics and factors
      related to treatment. RESULTS:: Ninety-one practitioners and 347 patients were
      recruited. Demographic characteristics of recruited orthodontists were similar to
      those of American Association of Orthodontists members. The great majority of
      practitioners reported using fixed appliances and elastics frequently for adult
      AOB patients. Only a third of practitioners reported using aligners frequently
      for adult AOB patients, and 10% to 13% frequently recommended temporary anchorage
      devices (TADs) or orthognathic surgery. Seventy-four percent of the patients were
      female, and the mean age was 31.4 years. The mean pretreatment overbite was -2.4
      mm, and the mean mandibular plane angle was 38.8 degrees . Almost 40% of patients
      had undergone orthodontic treatment previously. CONCLUSIONS:: This article
      presents the demographic data for 91 doctors and 347 adult AOB patients, as well
      as the practitioners' self-reported treatment preferences.

PMID- 30207488
TI  - Enzalutamide after chemotherapy in advanced castration-resistant prostate cancer:
      the Italian Named Patient Program.
AB  - AIM: To collect efficacy and safety data of enzalutamide after docetaxel, we
      retrospectively evaluated the Italian Named Patient Program results. PATIENTS &
      METHODS: Two hundred and nine metastatic castration-resistant prostate cancer
      patients were enrolled. Median age was 73 years. Total 42.1% patients had pain,
      14.4% had a performance status of two and 59.8% had a Gleason score >=8. Total
      31.1% had previously received >=2 chemotherapies, 15.3 and 12% had been
      previously treated with abiraterone and cabazitaxel, respectively and 14.8% had
      received both. RESULTS:  Median progression-free survival and overall survival
      were 4.8 and 13.1 months, respectively. A prostate-specific antigen reduction
      >=50% was observed in 49.1%. Total 32.7% abiraterone-pretreated patients achieved
      a biochemical response compared with 56% of abiraterone-naive patients.
      CONCLUSION:  Enzalutamide was safe and well tolerated. Its antitumor activity in
      abiraterone-pretreated patients was limited.

PMID- 30207491
TI  - Switched On: How the Timing of Aversive Content in Traffic Safety Videos Impact
      Psychophysiological Indicators of Message Processing.
AB  - This study investigates how timing of the introduction of unpleasant emotional
      tone in a traffic safety video impacts the intensity of the viewer's emotional
      experience. Traffic safety advertising is a multi-million-dollar business in the
      United States. In many instances, 30-60 s ads are produced to raise awareness of
      the consequences of unsafe behaviors with the expectation that simply providing
      information will motivate safer behaviors. Producing videos intended to generate
      behavior change requires a complex understanding of what motivates behavior.
      Behavior change theory, neuroscience, and psychophysiology all provide guidance
      to improve the persuasive power of traffic safety videos. This study consisted of
      a 3 (message tone) * 3 (video) * 4 (order) repeated measures within subjects
      designed experiment. Participants (N = 75) were 20-30-year-old men who were shown
      nine traffic safety videos. Arousal intensity, attention, and negative emotion
      were tracked with the psychophysiological measures of skin conductance (measuring
      intensity of arousal), heart rate (measuring attention paid during the video),
      and corrugator muscle activation (measuring the negative emotional experience).
      Videos with three different aversive tones were used, low, high, and videos in
      which the tone switched from low to high aversive. Aversive tone is defined as
      stimuli that motivate a desire to escape or avoid something like death or pain.
      All videos were designed to prevent motor vehicle crashes. The results obtained
      from this study indicate that when attempting to persuade males aged 20-30 to
      practice safer driving behaviors, switched message tone appears to be the most
      effective message design in terms the intensity of emotional arousal and
      maintenance of attention.

PMID- 30207489
TI  - The Italian Mastocytosis Registry: 6-year experience from a hospital-based
      registry.
AB  - AIM: We collected 'real-life' data on the management of patients with
      mastocytosis in the Italian Mastocytosis Registry. METHODS: Six hundred patients
      diagnosed with mastocytosis between 1974 and 2014 were included from 19 centers.
      RESULTS: Among adults (n = 401); 156 (38.9%) patients were diagnosed with
      systemic mastocytosis. In 212 adults, no bone marrow studies were performed
      resulting in a provisional diagnosis of mastocytosis of the skin. This diagnosis
      was most frequently established in nonhematologic centers. In total, 182/184
      pediatric patients had cutaneous mastocytosis. We confirmed that in the most
      patients with systemic mastocytosis, serum tryptase levels were >20 ng/ml and KIT
      D816V was detectable. CONCLUSION: The Italian Mastocytosis Registry revealed some
      center-specific approaches for diagnosis and therapy. Epidemiological evidence on
      this condition is provided.

PMID- 30207490
TI  - Triglyceride glucose and haemoglobin glycation index for predicting outcomes in
      diabetes patients with new-onset, stable coronary artery disease: a nested case
      control study.
AB  - AIM: Previous studies have shown that both triglyceride glucose (TyG) and
      haemoglobin glycation indexes (HGI) are predictors of cardiovascular risk.
      However, the prognostic value of TyG index and HGI in patients with type 2
      diabetes mellitus (T2DM) and stable coronary artery disease (CAD) is not
      determined. METHODS: We conducted a nested case-control study among 1282 T2DM
      patients with stable CAD. Patients were followed up for 3846 person-years. A
      total of 160 patients with events (12.5%) were identified and matched
      individually on age, gender, previous use of lipid lowering agents and duration
      of follow-up with 640 controls. RESULTS: In Kaplan-Meier analysis, the upper
      tertiles of TyG index and HGI had a significant lower event-free survival (p =
      .002; p = .036, respectively). Of the note, both TyG index and HGI were
      associated with increased risk of MACCEs after adjusting for confounding risk
      factors [adjusted HR (95% CI): 1.693 (1.238-2.316); 1.215 (1.046-1.411),
      respectively]. Moreover, adding TyG index to the Cox model increased the C
      statistic to 0.638 (95%CI: 0.595-0.683, p = .002) while the C-statistic was not
      statistically improved when HGI was included (p = .240). CONCLUSIONS: Both TyG
      index and HGI could predict cardiovascular outcomes in T2DM patients with new
      onset, stable CAD while TyG index might be better. Key messages Both TyG and HGI
      are predictors of cardiovascular risk. The prognostic value of TyG index and HGI
      in T2DM patients with stable coronary artery disease is not determined. Our study
      firstly indicates that TyG index might have better prognostic value than HGI in
      T2DM patients with new-onset, stable CAD.

PMID- 30207492
TI  - Oral health status of pregnant women in Ilorin, Nigeria.
AB  - Oral diseases have been shown to negatively affect pregnancy outcomes, yet,
      routine oral health care is not a component of the antenatal care package in
      Nigeria. This study was designed to describe the pattern of the oral conditions
      in pregnancy compared to the non-pregnant controls. Two hundred and twenty-five
      pregnant women and 166 non-pregnant controls were studied from two healthcare
      facilities in Ilorin. Oral-related complaints were assessed in the pregnant
      population while both of the groups had an oral cavity examination. The mean age
      of the respondents was 28.24 years +/-4.77 and 80% had at least a secondary
      school level of education. The prevalence of oral complaints among the pregnant
      women was 19.1%. Gingivitis was more common among the pregnant women than the non
      pregnant women, and more demonstrable on examination. Oral healthcare should be a
      component of the antenatal care in our environment. Impact statement What is
      already known on this subject? Women experience oral disorders in pregnancy,
      which may be worsened by the physiological changes in pregnancy. What do the
      results of this study add? This study has demonstrated a higher prevalence of
      gingivitis in the pregnant women than in the non-pregnant women on oral
      examination. The signs of gingivitis were higher than its related complaints.
      What are the implications of these findings for clinical practice and/or further
      research? Therefore, dental care and an examination should be part of a routine
      antenatal care package to prevent the unwanted pregnancy outcomes that are
      related to oral disorders.

PMID- 30207493
TI  - Retroperitoneal hematoma secondary to spontaneous rupture of ovarian artery
      pseudoaneurysms: case report and review of literature.

PMID- 30207494
TI  - Perineal outcome following educational intervention: a retrospective audit of
      primiparous women.
AB  - The management of vaginal delivery appears to offer an opportunity to reduce the
      morbidity of pelvic floor dysfunction (PFD) which is very common in the
      postpartum period. Research by the authors suggests that an episiotomy is
      protective against PFD, in particular urinary incontinence. The aim of this
      subsequent audit was to see if educational intervention can alter the common
      medical practice of episiotomy and in turn reduce postpartum PFD. Nine hundred
      and fifty four primiparous women with a non-instrumental vaginal delivery were
      included, of which 30% had an intact perineum, 51% a spontaneous tear and 19% an
      episiotomy. The intervention was a teaching session by the Head of Urogynaecology
      encompassing the anatomy, the impact of a vaginal delivery on PFD, in addition to
      local and international research. Whilst no significant difference was noted
      overall in the episiotomy rates as a result of the educational intervention (p =
      .17), significant differences were noted with the different accoucheur types.
      Where the accoucheur was an obstetrician or obstetrics registrar, the episiotomy
      rates increased from 56% to 70% (p < .01); where the midwife was the accoucheur
      the episiotomy rate changed minimally (11-18%, respectively; p = .27). This
      demonstrates that feedback about the provider's own practice patterns can change
      the behaviour to conform with the agreed upon standards. Impact Statement What is
      already known on this subject? Pelvic floor dysfunction (PFD) is the most common
      complication of childbirth, affecting approximately 85% of Australian women
      following a vaginal delivery. A link has been made between the perineal outcome
      and PFD, which has a significant impact on the quality of life. Previous research
      suggests that the management of a vaginal delivery offers an opportunity to
      reduce its morbidity, with an episiotomy being protective. However, there is a
      wide variation in the use of episiotomy which ranges from 9% to 100%. What the
      results of this study add? The literature suggests that the strongest factor
      associated with the episiotomy rates arises from differences in the attitude and
      training. Consequently, this study explored whether an educational intervention
      can change the common medical practice of episiotomy and in turn reduce
      postpartum PFD. What are the implications of these findings for clinical practice
      and/or further research? No significant difference was noted overall in the
      episiotomy rates as a result of the educational intervention, however, the
      response to the educational intervention was varied among the different types of
      accoucheurs with the obstetricians, obstetric registrars and student midwives
      significantly increasing their rate of episiotomy, whilst the midwives
      demonstrated no significant change. This suggests that there are contributing
      factors which may include past education and experience; this is an area for
      further research.

PMID- 30207495
TI  - Effects of Watermelon Powder and l-arginine Supplementation on Azoxymethane
      Induced Colon Carcinogenesis in Rats.
AB  - Diets high in fruits and vegetables may help prevent colorectal cancer (CRC).
      Watermelon consumption may reduce CRC risk due to its concentration of l
      citrulline and its role in endothelial nitric oxide (NO) production. Research
      suggests that increased NO levels have tumoricidal effects. The purpose of this
      study was to determine the effects of watermelon powder supplementation on
      aberrant crypt foci (ACF) formation, precancerous lesions, and expression of
      genes associated with colon carcinogenesis. Thirty-two male Sprague-Dawley rats
      were assigned into three groups: control, 0.36% l-arginine, or 0.5% watermelon
      powder and injected with azoxymethane (15 mg/kg body weight). Both l-arginine and
      watermelon powder groups exhibited lower total numbers of ACF and high
      multiplicity ACF (P < 0.01). The watermelon powder group exhibited higher NO
      levels and lower 8-hydroxyguanosine DNA damage (P < 0.05). Watermelon powder and
      l-arginine downregulated 8-oxoguanine DNA glycosylase gene expression and
      upregulated O6-methylguanine DNA methyltransferase gene expression (P < 0.05).
      Cyclooxgenase-2 gene expression was lower for rats fed with watermelon powder (P
      < 0.05). These results suggest that watermelon powder or l-arginine
      supplementation may reduce the risk of colon cancer by suppressing ACF formation
      through lowering oxidative DNA damage and inflammation, modulating DNA repair
      enzyme expression, and/or enhancing NO production.

PMID- 30207497
TI  - Cardioversion for atrial fibrillation - how to prevent thromboembolic
      complications?
AB  - Cardioversion is an essential component of rhythm control strategy for atrial
      fibrillation. The thromboembolic risk of cardioversion is well established and
      the mechanisms behind the phenomenon have been comprehensively described. There
      are several clinical aspects that are important to take into consideration when
      assessing the safety of cardioversion. Before proceeding to cardioversion, the
      probability of early treatment failure and antiarrhythmic treatment options to
      prevent recurrences should be carefully evaluated to avoid the risks of repeated
      futile cardioversions. Effective periprocedural anticoagulation is the mainstay
      in thromboembolic complication prevention and the first week after rhythm
      conversion is the most vulnerable period in this respect. Early timing of
      cardioversion appears to be another important measure to decrease the risk of
      thromboembolic complications. Transoesophageal echocardiography is useful in
      clinical scenarios where early cardioversion is desirable due to debilitating
      clinical symptoms and a short duration of arrhythmia or the adequacy of preceding
      anticoagulation is uncertain. However, it does not lessen the need for effective
      anticoagulation after cardioversion. This review summarizes the recent scientific
      discoveries to improve the safety of cardioversion for atrial fibrillation. Key
      messages Cardioversion for atrial fibrillation entails a significant risk of
      thromboembolic complications, especially during the first week after the
      procedure. The intensity of periprocedural anticoagulation and the timing of
      cardioversion appear to be significant determinants of the risk of
      thromboembolism. Awareness of the clinical aspects influencing cardioversion
      safety should be raised.

PMID- 30207496
TI  - Artificial oocyte activation: physiological, pathophysiological and ethical
      aspects.
AB  - : Infertile couples with low oocyte yield in combination with abnormal semen
      parameters may experience intra-cytoplasmic sperm injection (ICSI) failure. An
      established factor associated with ICSI failure is oocyte activation deficiency
      (AOD). The latter originates from seminal contributors, such as phospholipase C
      zeta (PLCzeta) that is not adequate to produce calcium (Ca2+) oscillations for
      oocyte activation. Apart from this natural activator, other stimulants, such as
      A23187, ionomycin, strontium chloride or even electric pulses, have been used in
      embryological laboratories to overcome AOD and ICSI failure. The aim of the
      present narrative review is to discuss the role of Ca+2 oscillations in oocyte
      activation and summarize the evidence concerning the use of oocyte activators as
      agents for artificial oocyte activation (AOA). Studies in humans and animals have
      emerged many physiological, pathophysiological and ethical aspects of AOA. In
      conclusion, in mammalian eggs, the cytosolic Ca+2 oscillations derive from a
      periodic release of Ca+2 from intracellular pools. PLCzeta, as well as artificial
      stimulants, have been used to produce Ca+2 oscillations for AOA. As the latter
      may increase the risk of epigenetic induced malformations, further studies are
      required to clarify whether AOA constitutes an effective and safe method to
      overcome ICSI failure. ABBREVIATIONS: AOA: artificial oocyte activation; AOD:
      oocyte activation deficiency; Ca+2: Calcium; CAMKII: Ca+2/calmodulin-dependent
      protein kinase II; CICR: calcium-induced calcium-release; DAG: diacylglycerol; GM
      CSF: granulocyte-macrophage colony-stimulating factor; ICSI: intra-cytoplasmic
      sperm injection; InsP3R: inositol-trisphosphate receptor; IP3: inositol 1,4,5
      trisphosphate; IVF: in vitro fertilization; MAP: mitogen-activated protein; MII:
      metaphase II; NADP: nicotinic acid adenine dinucleotide phosphate; NO: nitric
      oxide; PAWP: post-acrosomal WW-binding domain protein; PIP2: phosphatidylinositol
      4,5-bisphosphate; PLC: phospholipase C; PLCzeta: phospholipase C-zeta; SOAFs:
      spermatozoon-released oocyte-activating factors; Sr+2: strontium; TFF: total
      fertilization failure.

PMID- 30207498
TI  - Interprofessional student meetings in municipal health service - Mutual learning
      towards a Community of Practice in patient care.
AB  - Mutual engagement is fundamental in interprofessional collaboration. This paper
      investigated how mutual engagement evolves in interprofessional student meetings
      when medical, nursing, occupational therapy and physiotherapy students shape
      their own collaboration and learning in patient care. We conducted a qualitative
      study with an ethnographic design. The data material consists of 200 hours of
      observations across nine student groups and two informal conversations with each
      student group during a two-week clinical placement in the period of 2014-2015.
      The interprofessional student meetings and the informal conversations were audio
      recorded, and field notes were prepared from our observations of the student
      activities. In the data analysis, we relied on an interpretative thematic
      analysis and used the sociocultural theory of learning as an interpretative
      framework. The analysis showed that mutuality evolved through three types of
      mutual engagement: facilitating interactions, actual interactions and clarifying
      further interactions. In conclusion, complex mutual engagement in patient care
      evolved and was maintained in interprofessional student meetings when the
      students had an explicit opportunity to shape their own interprofessional
      collaboration and learning. The students' opportunity to shape the
      interprofessional collaborative practice in patient care themselves appeared to
      be a criterion for success.

PMID- 30207499
TI  - Self-reported reproductive health experiences in women with von Willebrand
      disease: a qualitative interview-based study.

PMID- 30207500
TI  - Insights into Bacterial Milk Spoilage with Particular Emphasis on the Roles of
      Heat-Stable Enzymes, Biofilms, and Quorum Sensing.
AB  - Milk spoilage caused by psychrotrophic bacteria and their heat-stable enzymes is
      a serious challenge for the dairy industry. In many studies, spoilage has been
      explored based on the simplistic view of undesirable enzymes produced by
      planktonic cells. Recently, biofilms and quorum sensing (QS) have been suggested
      as important factors in the deterioration of milk, which opens new avenues for
      investigation of the processes and challenges. Production and heat stability of
      enzymes are enhanced in biofilms, mainly because of inherent differences in
      physiological states and protective shielding by extracellular polymeric
      substances. QS plays a key role in modulating expression of hydrolytic enzymes
      and biofilm formation. To date, few studies have been conducted to investigate
      the complex interplays of enzyme production, biofilm formation, and QS. This
      review provides novel insights into milk spoilage with particular emphasis on the
      roles of biofilms and QS and summarizes potential effective strategies for
      controlling the spoilage of milk.

PMID- 30207501
TI  - Periumbilical infiltration of lidocaine with epinephrine for postoperative pain
      reduction in single-port laparoscopic adnexal surgery.
AB  - An efficient and simple approach to control postoperative pain in transumbilical
      single-port laparoscopic surgery appears necessary. We conducted a retrospective
      analysis in a study group (80 patients who received periumbilical infiltration of
      lidocaine with epinephrine before their incisional site repair completion) and
      control group (80 patients who received no analgesic at their incisional site
      repair completion) matched for their age, body mass index and their frequency of
      previous abdominal surgery. The pain scores based on the numerical rating scale
      (NRS) and the analgesic use frequency during the postoperative period were
      evaluated. The postoperative pain scores based on the NRS were significantly
      lower in the study group than in the control group immediately after the
      operation and at postoperative 6 hours. The postoperative analgesic use frequency
      during the hospital stay and the pain scores at 24 and 48 hours were not
      significantly different between the two groups. Periumbilical infiltration of
      lidocaine with epinephrine can reduce surgical pain until 6 hours,
      postoperatively. Impact statement What is already known on this subject? No
      consensus on whether single port laparoscopic surgery significantly reduces
      postoperative pain, as compared to conventional laparoscopy exists, and the
      immediate postoperative pain seems to be severe even with the SPL surgery. What
      do the results of this study add? The periumbilical infiltration of lidocaine
      with epinephrine can alleviate surgical pain until 6 hours, postoperatively. What
      are the implications of these findings for clinical practice and/or further
      research? Our result may provide an efficient and simple approach to control
      postoperative pain in a single port laparoscopic surgery.

PMID- 30207502
TI  - Prenatal diagnosis of intracranial malignant mass in a twin pregnancy: a case
      report.

PMID- 30207503
TI  - Preoperative diagnosis of atypical pelvic leiomyoma and sarcoma: the potential
      role of diffusion-weighted imaging.
AB  - The objective of our study was to determine the utility of diffusion-weighted
      magnetic resonance (DWMR) to differentiate the atypical uterine leiomyomas and
      sarcomas, establishing a cut-off value of the apparent diffusion coefficient
      (ADC) to rule out the malignancy. We performed a diagnostic accuracy
      retrospective study including 10 patients with pelvic sarcomas and 17 patients
      with leiomyomas. Atypical morphological features in magnetic resonance (MR)
      studies occurred in 58.8% of the patients, leading to a significant number of
      indeterminate diagnoses. In contrast, ADC values were consistent for leiomyomas,
      sarcomas, primary tumours, recurrences, intrauterine and in the extrauterine
      pelvic locations. The ADC cut-off value was set in 1 (*10-3 mm2/s). Thus, the ADC
      values equal or superior to 1 * 10-3 mm2/s were always associated with a
      leiomyoma. The structural MR accuracy was 66.7%, reaching 100% when using DWMR
      with dichotomised ADC values. Diffusion-weighted imaging with the quantitative
      measurement of ADC may be considered a useful preoperative test for the
      differentiation of atypical leiomyomas from sarcomas. Impact statement What is
      already known on this subject? Papers reporting the utility of a diffusion
      weighted MR for the diagnosis of uterine sarcomas are scarce and consist of a
      small series. However, the published results are consistent with our study, with
      the decreased ADCs in the case of malignancy. What do the results of this study
      add? The main differential characteristic of our study is that we selected only
      the atypical leiomyomas: they share sonographic and MR features with sarcomas,
      which often leads to an inaccurate diagnosis. This is also the first paper
      reporting on the role of DWMR with ADC for these types of tumours in extrauterine
      pelvic locations. We demonstrated a consistent relationship between dichotomised
      ADC values in leiomyomas/sarcomas for these particular cases and in recurrent
      tumours, with no overlap between both the groups, as a difference with the
      previous reports. What are the implications of these findings for clinical
      practice and/or further research? Our study can be considered as a proof of
      concept supporting DWMR with ADC measurement as a useful tool to enhance the
      diagnostic accuracy of MR, highlighting its value to rule out malignancy. Hence,
      DWMR seems to be a potential useful test to include in the preoperative
      evaluation of clinically atypical uterine tumours.

PMID- 30207504
TI  - Clozapine attenuates mitochondrial burdens and abnormal behaviors elicited by
      phencyclidine in mice via inhibition of p47 phox; Possible involvements of
      phosphoinositide 3-kinase/Akt signaling.
AB  - BACKGROUND:: Oxidative stress and mitochondrial dysfunction have been implicated
      in the pathophysiology of schizophrenia. AIMS:: We investigated whether
      antipsychotic clozapine modulates nicotinamide adenine dinucleotide phosphate
      oxidase and mitochondrial burdens induced by phencyclidine in mice. METHODS:: We
      examined the effect of clozapine on nicotinamide adenine dinucleotide phosphate
      oxidase activation, mitochondrial burdens (i.e. oxidative stress and
      mitochondrial dysfunction), and activities of enzymatic antioxidant in the
      prefrontal cortex, and subsequent abnormal behaviors induced by repeated
      treatment with phencyclidine. p47 phox Knockout mice and LY294002, a
      phosphoinositide 3-kinase inhibitor, were employed to elucidate the
      pharmacological mechanism of clozapine. RESULTS:: Phencyclidine treatment
      resulted in an early increase nicotinamide adenine dinucleotide phosphate oxidase
      activity, membrane translocation of p47 phox, interaction between p-Akt and p47
      phox, and mitochondrial burdens in wild-type mice. Although these increases
      returned to near control level four days post-phencyclidine, mitochondrial
      superoxide dismutase and glutathione peroxidase activities were decreased at that
      time. Clozapine, LY294002, or p47 phox knockout significantly ameliorated social
      withdrawal and recognition memory deficits produced by phencyclidine.
      Importantly, LY294002 did not significantly alter the effects of clozapine
      against abnormal behaviors and the interaction between p-Akt and p47 phox induced
      by phencyclidine. Furthermore, neither LY294002 nor clozapine exhibited any
      additive effects to the protection afforded by p47 phox knockout against
      phencyclidine insult. CONCLUSION:: Our results suggest that p47 phox gene
      mediates phencyclidine-induced mitochondrial burdens and abnormal behaviors, and
      that the interactive modulation between p47 phox and phosphoinositide 3
      kinase/Akt is important for the understanding on the pharmacological mechanism of
      clozapine.

PMID- 30207505
TI  - Involvement of the Hypothalamic Glutamatergic System in the Development of
      Radiation-Induced Pica in Rats.
AB  - Since the peripheral serotoninergic pathway is involved in the development of
      radiation-induced nausea and vomiting, referred to as radiation sickness,
      serotonin 5-HT3 receptor antagonists are used as a preventive measure, although
      patients still suffer from these symptoms. Glutamate is known as the excitatory
      neurotransmitter and is involved in various autonomic symptoms. We investigated
      the effect of radiation on glutamate release in rats, as measured by in vivo
      brain microdialysis, and the effects of glutamate receptor antagonists on
      radiation-induced pica, which can be used as a behavioral assessment of radiation
      sickness in rats. A microdialysis probe was inserted into the hypothalamus of
      rats that received 4 Gy total-body irradiation (TBI) with or without pretreatment
      of 5-HT3 receptor antagonist (granisetron, 0.1 mg/kg, i.p.), and dialysates were
      collected for 3 h after TBI and subjected to HPLC assay of glutamate. In
      addition, rats were intracerebroventricularly injected with NMDA receptor
      antagonist (MK-801: 3 MUg/rat) or AMPA receptor antagonist (CNQX: 1 MUg/rat)
      before TBI, and radiation-induced pica was determined. An increase in glutamate
      release was observed within 1 h postirradiation. The increased glutamate release
      was suppressed by granisetron. We also found that CNQX, but not MK-801,
      effectively inhibited radiation-induced pica. These results indicate that the
      hypothalamic glutamatergic system contributes to radiation-induced pica through
      the AMPA receptors.

PMID- 30207506
TI  - The impact of chronic carbohydrate manipulation on mucosal immunity in elite
      endurance athletes.
AB  - Carbohydrate (CHO) availability could alter mucosal immune responses to exercise.
      This study compared the effect of three dietary approaches to CHO availability on
      resting and post-exercise s-IgA levels. Elite race walkers (n = 26) adhered to a
      high CHO diet (HCHO), periodised CHO availability (PCHO) or a low CHO/high fat
      diet (LCHF) for 3 weeks while completing an intensified training program. HCHO
      and PCHO groups consumed 8.0-8.5 g.kg-1 CHO daily, with timing of ingestion
      manipulated to alter CHO availability around key training sessions. The LCHF diet
      comprised 80% fat and restricted CHO to < 50 g.day-1. A race walk test protocol
      (19 km females, 25 km males) was completed at baseline, after adaptation, and
      following CHO restoration. On each occasion, saliva samples were obtained pre-
      and post-exercise to quantify s-IgA levels. Resting s-IgA secretion rate
      substantially increased ~ two-fold post-intervention in all groups (HCHO: 2.2 +/-
      2.2, PCHO: 2.8 +/- 3.2, LCHF: 1.6 +/- 1.6; fold-change+/- 95% confidence limits),
      however, no substantial differences between dietary treatments were evident. Post
      exercise, substantial 20-130% increases in s-IgA concentration and 43-64%
      reductions in flow rate occurred in all dietary treatments, with trivial
      differences evident between groups. It appears that high volume training
      overrides any effect of manipulating CHO availability on mucosal immunity in
      elite athletes.

PMID- 30207507
TI  - Proofs for implementation of higher HE4 and ROMA index cut-off values in ovarian
      cancer preoperative stratification.
AB  - This study aimed to identify and quantify the clinical significance of the HE4
      and ROMA index in patients with an adnexal tumour. We recruited 159 women and the
      HE4 and CA125 were measured with an electrochemiluminescence immunoassay in the
      sera. We used the Kolmogorov-Smirnov test, Mann-Whitney's test and logistic
      regression to interpret the data. In the premenopausal group (n = 57), the ROC
      analysis (with cut-off: 86.1 pmol/L for HE4; 40.7 U/L for CA125 and 21.9% for
      ROMA) demonstrated the superior prognostic potential of those markers when the
      higher cut-offs used are compared to producers. The AUC for HE4/CA125/ROMA were
      0.846/0.867/0.846, respectively. The HE4/ROMA showed 85.7% sensitivity and 94%
      specificity. In the postmenopausal group (n = 102), the ROC analysis cut-off
      values were: 99.8 pmol/L for HE4; 45.8 U/L for CA125 and 38.4% for ROMA. AUC for
      HE4/CA125/ROMA were 0.928/0.899/0.927, respectively. HE4 had an 86.1% sensitivity
      at 92.4% specificity, while ROMA showed an 88.9% sensitivity at a 90.9%
      specificity. Impact Statement What is already known on this subject? The
      incidence of ovarian cancer has been increasing, despite the improvement of
      diagnostic, operative and therapeutic procedures. As a part of the
      multiparametric approach, the HE4 and ROMA index improve the diagnostic
      sensitivity and specificity of CA125 in the detection of ovarian cancer. What the
      results of this study add? The evaluation of HE4 and ROMA efficacy in the
      preoperative stratification was made by logistic regression analysis. The better
      prognostic potential of ROMA index, in patients with present adnexal mass, was
      obtained using our higher cut-offs for the ROMA index (21.9% for premenopausal
      and 38.4% for postmenopausal) in comparison to the producer's (11.7% for
      premenopausal and 29.9% for postmenopausal). The HE4 and ROMA index had 14.29
      +LR, 0.15 -LR, 67% PPV and 97.9% NPV in the premenopausal patients. In the
      postmenopausal group, the HE4 had 11.37 +LR, 0.15 -LR, 75.6% PPV and 92.4% NPV,
      the ROMA showed 9.78 +LR, 0.12 -LR, 91.2% PPV and 95.2% NPV. What the
      implications are of these findings for clinical practice and/or further research?
      Application of a higher cut-off for HE4/CA125/ROMA index can significantly reduce
      the percentage of FP and FN in the preoperative stratification of ovarian cancer
      and justify speculations about this subject in the future.

PMID- 30207509
TI  - Primary omental ectopic pregnancy: a case report.

PMID- 30207508
TI  - Environmental toxicant induced epigenetic transgenerational inheritance of
      ovarian pathology and granulosa cell epigenome and transcriptome alterations:
      ancestral origins of polycystic ovarian syndrome and primary ovarian insufiency.
AB  - Two of the most prevalent ovarian diseases affecting women's fertility and health
      are Primary Ovarian Insufficiency (POI) and Polycystic Ovarian Syndrome (PCOS).
      Previous studies have shown that exposure to a number of environmental toxicants
      can promote the epigenetic transgenerational inheritance of ovarian disease. In
      the current study, transgenerational changes to the transcriptome and epigenome
      of ovarian granulosa cells are characterized in F3 generation rats after
      ancestral vinclozolin or DDT exposures. In purified granulosa cells from 20-day
      old F3 generation females, 164 differentially methylated regions (DMRs) (P < 1 x
      10-6) were found in the F3 generation vinclozolin lineage and 293 DMRs (P < 1 x
      10-6) in the DDT lineage, compared to controls. Long noncoding RNAs (lncRNAs) and
      small noncoding RNAs (sncRNAs) were found to be differentially expressed in both
      the vinclozolin and DDT lineage granulosa cells. There were 492 sncRNAs (P < 1 x
      10-4) in the vinclozolin lineage and 1,085 sncRNAs (P < 1 x 10-4) in the DDT
      lineage. There were 123 lncRNAs and 51 lncRNAs in the vinclozolin and DDT
      lineages, respectively (P < 1 x 10-4). Differentially expressed mRNAs were also
      found in the vinclozolin lineage (174 mRNAs at P < 1 x 10-4) and the DDT lineage
      (212 mRNAs at P < 1 x 10-4) granulosa cells. Comparisons with known ovarian
      disease associated genes were made. These transgenerational epigenetic changes
      appear to contribute to the dysregulation of the ovary and disease susceptibility
      that can occur in later life. Observations suggest that ancestral exposure to
      toxicants is a risk factor that must be considered in the molecular etiology of
      ovarian disease.

PMID- 30207511
TI  - Occurrence of Foliar Pathogens of Watermelon on Commercial Farms in South
      Carolina Estimated with Stratified Cluster Sampling.
AB  - A survey of foliar pathogens of watermelon based on two-stage cluster sampling
      was conducted on commercial farms in South Carolina in spring 2015, spring and
      fall 2016, and fall 2017. In total, 60 fields from 27 different growers in seven
      counties representing the main watermelon-producing areas in the state were
      sampled, using a stratified two-stage cluster sampling approach. In the sampling
      design, counties corresponded to strata, growers to first-stage clusters, and
      fields to second-stage clusters. In each field, 100 symptomatic leaves were
      collected at five equidistant sampling points along four transects encompassing a
      square shape of 2,500 m2. After collection, pathogens were identified based on
      reproductive structures formed on leaves during >12 h incubation. Estimates were
      obtained for the statewide probability of pathogen occurrence and associations
      between pathogen pairs. Six fungal pathogens, Stagonosporopsis spp., Podosphaera
      xanthii, Cercospora citrullina, Colletotrichum orbiculare, Myrothecium sensu lato
      (s.l.), and Corynespora cassiicola; the oomycete Pseudoperonospora cubensis; and
      three viral pathogens were identified on the examined leaves. With the exception
      of fall 2017, Stagonosporopsis spp. was the most prevalent pathogen in every
      season, followed by P. xanthii. The highest occurrence of P. cubensis was in
      spring 2015; it did not occur in 2016. The highest occurrence of C. orbiculare
      was in spring 2016; it did not occur in spring 2015. Myrothecium s.l. was the
      most common pathogen in fall 2017 and the second most common pathogen occurring
      by itself in fall 2016. The third most common pathogen in fall 2017, Corynespora
      cassiicola, was not observed in any other season. Eight of the 80 isolates of
      Stagonosporopsis spp. collected were identified as S. caricae, the rest as S.
      citrulli. All isolates of S. caricae were found in spring 2015 and originated
      from two fields in different counties. A total of three positive and five
      negative associations were found between pathogen pairs co-occurring on the same
      leaf. A positive association between Stagonosporopsis spp. and C. citrullina was
      the only significant association between pathogens found in two seasons, spring
      2015 and spring 2016. Based on estimates of probability of pathogen occurrence
      across seasons, Stagonosporopsis spp. and P. xanthii are the most common
      pathogens on watermelons in South Carolina. This is the first report of C.
      cassiicola, S. caricae, and Myrothecium s.l. on watermelon in South Carolina.

PMID- 30207510
TI  - Prevalence and Genetic Diversity of Grabloviruses in Free-Living Vitis spp.
AB  - The distribution and diversity of grapevine red blotch virus (GRBV) and wild
      Vitis virus 1 (WVV1) (genus Grablovirus; family Geminiviridae) were determined in
      free-living Vitis spp. in northern California and New York from 2013 to 2017.
      Grabloviruses were detected by polymerase chain reaction in 28% (57 of 203) of
      samples from California but in none of the 163 samples from New York. The
      incidence of GRBV in free-living vines was significantly higher in samples from
      California counties with high compared with low grape production (chi2 = 83.09; P
      < 0.001), and in samples near (<5 km) to compared with far (>5 km) from vineyards
      (chi2 = 57.58; P < 0.001). These results suggested a directional spread of GRBV
      inoculum predominantly from vineyards to free-living Vitis spp. WVV1 incidence
      was also significantly higher in areas with higher grape production acreage (chi2
      = 16.02; P < 0.001). However, in contrast to GRBV, no differential distribution
      of WVV1 incidence was observed with regard to distance from vineyards (chi2 =
      0.88; P = 0.3513). Two distinct phylogenetic clades were identified for both GRBV
      and WVV1 isolates from free-living Vitis spp., although the nucleotide sequence
      variability of the genomic diversity fragment was higher for WWV1 (94.3 to 99.8%
      sequence identity within clade 1 isolates and 90.1 to 100% within clade 2
      isolates) than GRBV (98.3% between clade 1 isolates and 96.9 to 100% within clade
      2 isolates). Additionally, evidence for intraspecific recombination events was
      found in WVV1 isolates and confirmed in GRBV isolates. The prevalence of
      grabloviruses in California free-living vines highlights the need for vigilance
      regarding potential grablovirus inoculum sources in order to protect new vineyard
      plantings and foundation stock vineyards in California.

PMID- 30207512
TI  - "Who would want to die like that?" Perspectives on dying alone in a long-term
      care setting.
AB  - The discourse of dying alone is negatively weighted and models of a good death
      identify not dying alone as a key outcome. Understanding why dying alone is
      viewed negatively and its effects on care is a priority. In separate focus groups
      with long-term care residents, family caregivers, and staff, we identified
      evidence for four different perspectives on the importance of presence at the
      time of death. However, while each individual had their own unique perspective on
      dying alone, the predominant view expressed across respondent groups was that
      having human connection near the end of one's life was important.

PMID- 30207513
TI  - A school- and community-based intervention to promote healthy lifestyle and
      prevent type 2 diabetes in vulnerable families across Europe: design and
      implementation of the Feel4Diabetes-study.
AB  - OBJECTIVE: To describe the design of the Feel4Diabetes-intervention and the
      baseline characteristics of the study sample. DESIGN: School- and community-based
      intervention with cluster-randomized design, aiming to promote healthy lifestyle
      and tackle obesity and obesity-related metabolic risk factors for the prevention
      of type 2 diabetes among families from vulnerable population groups. The
      intervention was implemented in 2016-2018 and included: (i) the 'all-families'
      component, provided to all children and their families via a school- and
      community-based intervention; and (ii) an additional component, the 'high-risk
      families' component, provided to high-risk families for diabetes as identified
      with a discrete manner by the FINDRISC questionnaire, which comprised seven
      counselling sessions (2016-2017) and a text-messaging intervention (2017-2018)
      delivered by trained health professionals in out-of-school settings. Although the
      intervention was adjusted to local needs and contextual circumstances,
      standardized protocols and procedures were used across all countries for the
      process, impact, outcome and cost-effectiveness evaluation of the intervention.
      SETTING: Primary schools and municipalities in six European countries. SUBJECTS:
      Families (primary-school children, their parents and grandparents) were recruited
      from the overall population in low/middle-income countries (Bulgaria, Hungary),
      from low socio-economic areas in high-income countries (Belgium, Finland) and
      from countries under austerity measures (Greece, Spain). RESULTS: The
      Feel4Diabetes-intervention reached 30 309 families from 236 primary schools. In
      total, 20 442 families were screened and 12 193 'all families' and 2230 'high
      risk families' were measured at baseline. CONCLUSIONS: The Feel4Diabetes
      intervention is expected to provide evidence-based results and key learnings that
      could guide the design and scaling-up of affordable and potentially cost
      effective population-based interventions for the prevention of type 2 diabetes.

PMID- 30207514
TI  - Comparison of the Cepheid Xpert Xpress Flu/RSV Assay to in-house Flu/RSV triplex
      real-time RT-PCR for rapid molecular detection of Influenza A, Influenza B and
      Respiratory Syncytial Virus in respiratory specimens.
AB  - This study compared the performance of the commercially available Xpert Xpress
      Flu/RSV assay to an in-house FluAB/RSV triplex real-time RT-PCR assay for the
      detection of influenza A/B viruses and respiratory syncitial virus (RSV) from
      both nasopharyngeal aspirate (NPA) and nasopharyngeal flocked swab (NPS). A total
      of 20 external quality assurance (EQA) samples and 172 clinical respiratory
      samples were tested prospectively using both the Xpert Xpress Flu/RSV assay and
      the in-house FluAB/RSV triplex assay. For the EQA samples, concordance rate was
      100 % when tested with both assays. For clinical samples, there was 100 %
      agreement between the two assays for detection of influenza A and influenza B,
      96.7 % agreement for detection of RSV and 99.7 % agreement for negative results.
      With a shortened turnaround time and good diagnostic performance, application of
      the Xpert Xpress Flu/RSV assay can facilitate patient triage for prompt
      implementation of infection control measures and management of high-risk patients
      during influenza epidemics.

PMID- 30207516
TI  - Chitinophaga parva sp. nov., a new member of the family Chitinophagaceae,
      isolated from soil in a chemical factory.
AB  - A Gram-stain-negative bacterium, designated LY-1T, was isolated from the soil
      sample collected from a chemical factory in Fuyang city, Anhui province, China.
      Cells of strain LY-1T were strictly aerobic, non-motile and rod-shaped. Strain LY
      1T grew optimally at pH 7.0 and at 30-35  degrees C. The taxonomic position was
      investigated using a polyphasic approach. Phylogenetic analysis based on 16S rRNA
      gene sequences revealed that strain LY-1T was a member of the genus Chitinophaga
      and showed the highest sequence similarity to Chitinophaga costaii A37T2T (97.5
      %) and lower (<97.0 %) sequence similarity to other known Chitinophaga species.
      Chemotaxonomic analysis revealed that strain LY-1T possessed menaquinone-7 as the
      major isoprenoid quinone; and iso-C15 : 0 (46.4 %), C16 : 1omega5c (27.8 %) and
      iso-C17 : 0 3-OH (9.0 %) were the predominant fatty acids. The polar lipids of
      strain LY-1T consisted of phosphatidylethanolamine, three unidentified
      phosphoaminolipids, one unidentified phospholipid, four unidentified lipids, two
      unidentified aminolipids and two unidentified glycolipids. The genomic DNA G+C
      content of strain LY-1T was 52.4 mol% based on total genome calculations. The
      average nucleotide identity and the digital DNA-DNA hybridization value of the
      draft genomes between strain LY-1T and strain A37T2T were 76.8 and 19.8 %,
      respectively. Based on the phylogenetic and phenotypic characteristics,
      chemotaxonomic data, and DNA-DNA hybridization, strain LY-1T is considered a
      novel species of the genus Chitinophaga, for which the name Chitinophagaparva sp.
      nov. (type strain LY-1T=CCTCC AB 2018018T=KCTC 62444T) is proposed.

PMID- 30207518
TI  - Evaluating the microbial pattern of periprosthetic joint infections of the hip
      and knee.
AB  - PURPOSE: Periprosthetic joint infection (PJI) is a devastating complication that
      leads to enormous economic and health care complaints from affected patients. The
      aim of this study is to identify the causative pathogens responsible for PJI,
      evaluate temporal trends concerning the pathogen pattern and identify potential
      risk factors for PJI. METHODOLOGY: This was a retrospective study analysing a
      total of 937 patients suffering PJI of the hip or knee joint between 2003 and
      2011. RESULTS: In total, 394 patients (42.0 %) with total knee arthroplasty
      (TKA), 477 patients (50.9 %) with total hip arthroplasty (THA) and 64 patients
      (6.8 %) receiving a dual-head prosthesis had to be hospitalised due to PJI. In
      two cases (0.2 %), a simultaneous infection of TKA and THA occurred. The mean age
      of the study cohort was 70.85+/-11.68 years. The mean body mass index (BMI) was
      28.53+/-5.7. According to the Charlson comorbidity index, 2.99 % of the patients
      were classified as severity Grade 1, 13.98 % Grade 2, 40.02 % Grade 3 and 43.0 %
      Grade 4. Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus
      epidermidis (MRSE), methicillin-resistant Staphylococcus aureus (MRSA), coagulase
      negative Staphylococcus (CoNS), Streptococcus, and Enterococcus were the
      pathogens mainly responsible. An increase in high-resistance pathogens, such as
      MRSE, extended-spectrum beta-lactamase bacteria (ESBL), ampicillin-resistant
      Enterococcus, Acinetobacter spp. and vancomycin-resistant Enterococcus (VRE), was
      found during the study period. Only MRSA showed a declining tendency in a
      regression model. CONCLUSION: Patients suffering PJI present a certain risk
      profile with many comorbidities, e.g. high age and obesity. The observed
      microbiological pattern demonstrates the rise of high-resistance pathogens.

PMID- 30207515
TI  - The return of Pfeiffer's bacillus: Rising incidence of ampicillin resistance in
      Haemophilus influenzae.
AB  - Haemophilus influenzae, originally named Pfeiffer's bacillus after its discoverer
      Richard Pfeiffer in 1892, was a major risk for global health at the beginning of
      the 20th century, causing childhood pneumonia and invasive disease as well as
      otitis media and other upper respiratory tract infections. The implementation of
      the Hib vaccine, targeting the major capsule type of H. influenzae, almost
      eradicated the disease in countries that adapted the vaccination scheme. However,
      a rising number of infections are caused by non-typeable H. influenzae (NTHi),
      which has no capsule and against which the vaccine therefore provides no
      protection, as well as other serotypes equally not recognised by the vaccine. The
      first line of treatment is ampicillin, but there is a steady rise in ampicillin
      resistance. This is both through acquired as well as intrinsic mechanisms, and is
      cause for serious concern and the need for more surveillance. There are also
      increasing reports of new modifications of the intrinsic ampicillin-resistance
      mechanism leading to resistance against cephalosporins and carbapenems, the last
      line of well-tolerated drugs, and ampicillin-resistant H. influenzae was included
      in the recently released priority list of antibiotic-resistant bacteria by the
      WHO. This review provides an overview of ampicillin resistance prevalence and
      mechanisms in the context of our current knowledge about population dynamics of
      H. influenzae.

PMID- 30207519
TI  - Conventional culture method and qPCR using 16S rDNA for tissue bank: a comparison
      using a model of cardiac tissue contamination.
AB  - Real-time polymerase chain reaction (qPCR) using 16S rDNA is an alternative to
      conventional culture-based tests. The aim of this study was to compare the
      conventional culture method with qPCR using 16S rDNA in a model of cardiac tissue
      contamination. Samples of cardiac tissue for artificial contamination with
      Escherichia coli and control samples were submitted for DNA extraction, which was
      conducted by selective and alkaline lysis and purification steps. A standard
      curve for 16S rDNA was constructed to determine the efficiency and analytical
      sensitivity of the assay in concentrations from 106 to 102 c.f.u. ml-1 using
      TaqMan Master Mix. 16S rDNA was detected in all contaminated samples; however, it
      was not detected in the the final washing step solution of the sample with a
      bioburden of 102 c.f.u. ml-1. Using qPCR is a potential alternative to
      conventional culture for microbiological safety testing of allograft tissues for
      biobanking, reducing the time and labour input required.

PMID- 30207517
TI  - Bacillus shivajii sp. nov., isolated from a water sample of Sambhar salt lake,
      India.
AB  - A novel Gram-stain-positive, rod-shaped, motile, spore-forming, strictly aerobic,
      alkali- and halo- tolerant bacterium, designated strain AK72T, was isolated from
      a water sample collected from Sambhar salt lake, Rajasthan, India. The colony
      appears circular, shiny, smooth, translucent or slightly pale in colour and
      convex with an entire margin after 48 h incubation at 37  degrees C with pH 9.
      Growth of the bacterium occurred at 10-42  degrees C (optimum, 25-37  degrees C),
      at salinities of 0.5-10 % (w/v) NaCl (optimum 3-5 % NaCl) and pH of 6-10 (optimum
      pH 9). Strain AK72T was positive for oxidase, catalase, nitrate reductase,
      phenylalanine deaminase, ornithine decarboxylase, aesculinase, lipase and urease
      activities. The predominant fatty acids were iso-C15 : 0, anteiso-C15 : 0 and iso
      C16 : 0 and the cell-wall peptidoglycan contained meso-diaminopimelic acid as the
      diagnostic diamino acid. The major polar lipids of the strain were
      diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, an
      unidentified aminophospholipid, three unidentified phospholipids and three
      unidentified lipids. The genomic DNA G+C content of the strain AK72T was 36.8
      mol%. Phylogenetic analysis of the 16S rRNA gene sequence indicated that strain
      AK72T was closely related to Bacillus cellulosilyticus (96.5 %) and Bacillus
      vedderi (96.3 %), but the novel strain AK72T formed a separate clade with
      Bacillus aurantiacus whereas B. cellulosilyticus and B. vedderi were clustered in
      a separate clade. The above data in combination with the phenotypic
      characteristics and phylogenetic data inferred that strain AK72T represents a
      novel species of the genus Bacillus, for which the name Bacillusshivajii sp. nov.
      is proposed. The type strain is AK72T (=MTCC 12636T=KCTC 33981T=JCM 32183T).

PMID- 30207521
TI  - The 1943 Year Book of Dermatology and Syphilology.

PMID- 30207520
TI  - p15 encoded by Garlic virus X is a pathogenicity factor and RNA silencing
      suppressor.
AB  - Garlic virus X (GarVX) encodes a 15 kDa cysteine-rich protein (CRP). To
      investigate the function(s) of p15, its subcellular localization, role as a
      symptom determinant and capacity to act as a viral suppressor of RNA silencing
      (VSR) were analysed. Results showed that GFP-tagged p15 was distributed in the
      cytoplasm, nucleus and nucleolus. Expression of p15 from PVX caused additional
      systemic foliar malformation and led to increased accumulation of PVX, showing
      that p15 is a virulence factor for reconstructed PVX-p15. Moreover, using a
      transient agro-infiltration patch assay and a Turnip crinkle virus (TCV) movement
      complementation assay, it was demonstrated that p15 possesses weak RNA silencing
      suppressor activity. Removal of an amino acid motif resembling a nuclear
      localization signal (NLS) prevented p15 from accumulating in the nucleus but did
      not abolish its silencing suppression activity. This study provides the first
      insights into the multiple functions of the GarVX p15 protein.

PMID- 30207522
TI  - Vaccines Hesitancy and the Dermatologist.
AB  - As primary care providers and experts on diseases affecting the skin, such as
      herpes zoster (shingles) and human papillomavirus-related cancers, dermatologists
      are often asked to make important recommendations on vaccines and vaccinations;
      however, a rise in antivaccine attitudes-sometimes referred to as "vaccine
      hesitancy"-among patient populations, especially in North America and Europe, has
      created new challenges for the practicing dermatologist. Here we provide a brief
      overview of some of the major evidence that refutes commonly held misperceptions
      about vaccines.

PMID- 30207523
TI  - Can Sunscreens Harm Coral Reefs? Addressing Environmental Concerns and Offering
      Practical Recommendations.
AB  - The crucial role sunscreen plays in preventing sunburns, photoaging, and skin
      cancer is unquestionable, and as a result, it is incumbent upon dermatologists to
      influence patients to appropriately use sunscreens. In addition to explaining the
      benefits of sunscreen use and how to properly use sunscreen, dermatologists must
      also address possible barriers or concerns that patients may have regarding
      sunscreen. One concern that has gained increasing media attention in the recent
      years has been the environmental impact of sunscreens, especially the impact on
      coral reefs. There is strong evidence that some sunscreen ingredients, especially
      oxybenzone, are harmful to corals if the concentration in water is high. In some
      situations, primarily related to the number of swimmers and the geography of the
      shoreline, concentrations of oxybenzone far exceed the levels shown to be harmful
      to corals. As advocates for our patients' skin health, we need to be prepared to
      address this issue when asked, so that patients do not forgo sunscreen use in an
      effort to protect corals. This article will review evidence regarding the effects
      of sunscreen ingredients on corals and will provide practical guidance for
      counseling patients on how to select sunscreens that minimize the potential for
      harm to coral reefs.

PMID- 30207524
TI  - Effect of Fluprostenol Isopropyl Ester and 15-Keto Fluprostenol on Eyelash
      Growth: A Clinical and Pharmacologic Study.
AB  - 15-Keto fluprostenol isopropyl ester and 15-keto fluprostenol have demonstrated a
      stimulatory effect on the growth and thickening of the eyelashes without the
      disadvantages of the prostaglandin derivatives of the PGF2alpha group, which have
      a hydroxyl group at position 15 in their structure. The two 15-ketoderivatives
      have the same efficacy as the 15-hydroxyl derivatives in allowing the regrowth,
      lengthening, darkening, or thickening of the eyelashes, but without darkening the
      edge of the eyelid or coloring the iris, even temporarily.

PMID- 30207525
TI  - Nonuremic Calciphylaxis: Four Cases Associated with Autoimmune Diseases.
AB  - Calciphylaxis is a rare and severe syndrome of vascular calcification with
      unclear pathogenesis. This disease mainly affects patients with end-stage renal
      disease; however, it also has been described in nonuremic patients. We report
      four cases of nonuremic calciphylaxis (NUC) with ulcerated lesions associated
      with autoimmune disease. These cases support the literature suggesting that
      bisphosphonates and sodium thiosulfate are effective drugs in the treatment of
      calciphylaxis regardless of renal function.

PMID- 30207526
TI  - Efficacy of Folic Acid and Vitamin B12 Replacement Therapies in the Reduction of
      Adverse Effects of Isotretinoin: A Randomized Controlled Trial.
AB  - Previous studies have reported elevated homocysteine levels and folic acid and/or
      vitamin B12 deficiencies after isotretinoin therapy, which increase the risk of
      cardiovascular and neuropsychiatric disorders. Homocysteine is metabolized in the
      liver, a process requiring folate and vitamin B12. We conducted a randomized
      controlled trial to investigate whether folate and vitamin B12 replacement
      therapy with isotretinoin would be useful for preventing hyperhomocysteinemia. A
      total of 66 patients with acne were randomized into two groups: group A took
      isotretinoin, folic acid, and vitamin B12, whereas group B took isotretinoin
      alone. Treatment was continued for 2 months. Blood homocysteine, folic acid, and
      vitamin B12 levels were measured before and after treatment. In group A, a
      significant decrease in homocysteine level was observed after treatment
      (P=.0004), although it was still within the normal range. Folic acid and vitamin
      B12 levels significantly increased (P=.0026 and P=.0002, respectively). In group
      B, no significant changes were observed in the levels of homocysteine and vitamin
      B12, but folic acid levels decreased significantly (P=.02). We concluded that
      folic acid and vitamin B12 supplementation during isotretinoin therapy could be
      useful for preventing folate deficiency and improving blood homocysteine levels;
      this might as a result reduce the risks for cardiovascular and neuropsychiatric
      disorders in patients taking isotretinoin.

PMID- 30207527
TI  - A Case-Control Study in Primary Care Settings on the Roles of Dermatoscopy in
      Infectious Diseases Affecting the Skin, Part 1: Viral and Bacterial Infections.
AB  - We aimed to investigate roles of dermatoscopy in skin infections, with Part 1 of
      our report covering viral and bacterial infections. A case-control study was
      conducted on the medical records of all patients with skin infections who had had
      dermatoscopy performed over a period of 3 months. Our control participants were
      all patients with skin infections in two 3-month periods, and sex-pair-matched
      patients with the same infections, who had not undergone dermatoscopy. Records of
      523 study subjects were analyzed. Our first new finding was that dermatoscopy
      brought forward the diagnosis of herpes zoster by 1.62 days (95% confidence
      interval [CI] 0.29 to 0.34 days; z-score -2.18). Second, dermatoscopy facilitated
      the diagnosis of genital (P<.01) and small extragenital risk ratio [RR] 1.28, 95%
      CI 1.03 to 1.59) viral warts. Third, patients with genital herpes and/or genital
      warts and/or genital molluscum contagiosum diagnosed by clinical examination and
      dermatoscopy were significantly more willing to pay US$300 to investigate for
      other sexually transmitted infections (STIs) (RR 2.52, 95% CI 1.32 to 3.18), and
      bring partners for investigation (RR 1.32, 95% CI 1.12 to 1.55), compared to
      patients diagnosed by clinical examination alone. We performed dermatoscope
      guided laser ablation on viral warts, and dermatoscopy-guided excisional biopsy
      to confirm molluscum contagiosum. We conclude that dermatoscopy contributes to
      the diagnosis of some viral and bacterial infections. In addition, it may modify
      the help-seeking behaviour of patients with STIs.

PMID- 30207528
TI  - Tinea (Pityriasis) Obscurans: Don't Ignore the Spore!

PMID- 30207529
TI  - The Alphabetization of Lymphomatoid Papulosis: Focus on "F".

PMID- 30207530
TI  - Nigrites Linguae: An Unusual Presentation.

PMID- 30207531
TI  - The Largest Mass Poisoning in History: Arsenic Contamination of Well Water in
      Bangladesh.
AB  - Arsenic is a naturally occurring compound that is widely distributed in trace
      quantities in the environment. Levels toxic to humans have been found
      contaminating certain regions of the world and their groundwater, leading to
      deleterious effects. In fact, an estimated 150 million people are affected by
      arsenic contamination worldwide.1 Arsenic poisoning leads to several adverse
      health effects, including cancer of the lung, bladder, and kidney, neurologic
      disorders, cardiovascular disease, peripheral vascular disease, hypertension,
      pulmonary disease, and diabetes mellitus.2 Skin lesions are a common
      manifestation of arsenic poisoning. Early findings include diffuse or spotted
      melanosis, leukomelanosis, and depigmentation. Years of chronic arsenic poisoning
      can lead to acral keratoses and squamous cell carcinoma of the skin.3.

PMID- 30207532
TI  - Tinea Capitis Masquerading as Basal Cell Carcinoma.
AB  - A 52-year-old white man with alcoholic cirrhosis presented to the Mohs surgery
      clinic with a 1-month history of tender "bumps" located diffusely on his scalp.
      Two biopsies performed at an outside institution were read as "basal cell
      carcinoma" and "actinic keratosis." The patient was scheduled for a large
      excision of the scalp for presumed multiple nodules of basal cell carcinoma and
      desired a second opinion from our Mohs surgery clinic.

PMID- 30207533
TI  - Familial Dyskeratotic Comedones.
AB  - A 21-year-old man presented with extensive asymptomatic comedones and
      inflammatory papulonodules that had been present for the previous 7 years. The
      lesions had first appeared on the upper part of the trunk, subsequently spreading
      to the face, arms, axillae, thighs, groin, and buttocks. Physical examination
      revealed numerous monomorphic discrete black papules with firm central keratotic
      plugs. A few painful, inflamed nodules were present over the back (Figure 1).
      Pocklike scars were located predominantly over the face and back. His general
      health was otherwise normal, and he had not received any prior treatment for this
      condition. His father had similar lesions. Skin biopsy from the hyperkeratotic
      lesions revealed a crater-like invagination filled with lamellar keratinous
      material with foci of dyskeratosis (Figure 2).

PMID- 30207534
TI  - Ripple-Pattern Sebaceous Trichoblastoma.
AB  - A 28-year-old man of Middle-Eastern descent presented with a raised, pearly,
      slightly pigmented lesion on the right nasal ala. The lesion had been present for
      approximately 4 months. An excisional biopsy was taken, and the lesion measured
      1.0 cm * 0.9 cm in dimension. The cut surface revealed a firm, white to tan
      nodule located within the dermis. The patient had no other significant medical
      history. After the initial excision, the lesion did not recur.

PMID- 30207535
TI  - Recurrent Palisaded Neutrophilic and Granulomatous Dermatitis in the Setting of
      Systemic Lupus Erythematosus.
AB  - We present the case of a 66-year-old woman with a history of systemic lupus
      erythematosus, who presented with tender nodules on the forearms. The patient
      reported an 8-year history of pink bumps on the extensor surfaces of the forearms
      bilaterally that would arise episodically for a few weeks and subsequently
      resolve with no intervention. Her systemic lupus erythematosus was under good
      control with oral prednisone 10 mg daily, and the development of these lesions
      was not associated with concomitant flares of the systemic lupus erythematosus.

PMID- 30207536
TI  - Revisiting Flaps.

PMID- 30207537
TI  - Urgent Care Dermatology: Symptom-Based Diagnosis.

PMID- 30207539
TI  - Surface manipulation of a curved polycyclic aromatic hydrocarbon-based nano
      vehicle molecule equipped with triptycene wheels.
AB  - With a central curved chassis, a four-wheeled molecule-vehicle was deposited on a
      Au(111) surface and imaged at low temperature using a scanning tunneling
      microscope. The curved conformation of the chassis and the consequent moderate
      interactions of the four wheels with the surface were observed. The dI/dV
      constant current maps of the tunneling electronic resonances close to the Au(111)
      Fermi level were recorded to identify the potential energy entry port on the
      molecular skeleton to trigger and control the driving of the molecule. A lateral
      pushing mode of molecular manipulation and the consequent recording of the
      manipulation signals confirm how the wheels can step-by-step rotate while passing
      over the Au(111) surface native herringbone reconstructions. Switching a phenyl
      holding a wheel to the chassis was not observed for triggering a lateral
      molecular motion inelastically and without any mechanic push by the tip apex.
      This points out the necessity to encode the sequence of the required wheels
      action on the profile of the potential energy surface of the excited states to be
      able to drive a molecule-vehicle.

PMID- 30207541
TI  - CO-tip manipulation using repulsive interactions.
AB  - Understanding the interactions between a tip apex and a target atom or molecule
      is crucial for the manipulation of individual molecules with precise control by
      using scanning tunnelling microscopy (STM) and atomic force microscopy. Herein,
      we demonstrate the manipulation of target CO molecules on a Cu(111) substrate
      using a CO-functionalized W tip with atomic-scale accuracy. All experiments were
      performed in a home-built ultra-high vacuum STM system at 5 K. The CO-tip was
      fabricated by picking up a single CO molecule from a Cu(111) surface. In contrast
      to a metal tip, repulsive interactions occur between the CO-tip and the target CO
      molecule. This repulsive interaction promises perfect lateral hopping without any
      vertical hopping. Hopping events were directly monitored as sudden current drops
      in the simultaneously measured I-z curves. A larger barrier height between the CO
      tip and the target CO (~9.5 eV) was found from the slope of the I-z curve, which
      decreases the electron tunnelling probability between the tip and sample.
      Therefore, electron-driven manipulation cannot be a major trigger for the CO-CO
      repulsive manipulation. The CO-tip is able to manipulate only the target CO
      molecule, even when another CO molecule was located ~0.5 nm away. Statistical
      measurements revealed that the nearest neighbour atop site is the energetically
      stable position after hopping. However, if the CO target has another CO molecule
      in a neighbouring position (denoted as a 'pair'), the target CO hops more than
      twice as far. This means that the CO-tip experiences a larger repulsive
      interaction from the pair. These observations of CO-tip manipulation are useful
      for the design of two-dimensional artificial molecular networks as well as for
      developing a better understanding of catalytic oxidation processes.

PMID- 30207542
TI  - Prediction of fluid slip in cylindrical nanopores using equilibrium molecular
      simulations.
AB  - We introduce an analytical method to predict the slip length (L s) in cylindrical
      nanopores using equilibrium molecular dynamics (EMD) simulations, following the
      approach proposed by Sokhan and Quirke for planar channels [39]. Using this
      approach, we determined the slip length of water in carbon nanotubes (CNTs) of
      various diameters. The slip length predicted from our method shows excellent
      agreement with the results obtained from nonequilibrium molecular dynamics (NEMD)
      simulations. The data show a monotonically decreasing slip length with an
      increasing nanotube diameter. The proposed EMD method can be used to precisely
      estimate slip length in high slip cylindrical systems, whereas, L s calculated
      from NEMD is highly sensitive to the velocity profile and may cause large
      statistical errors due to large velocity slip at the channel surface. We also
      demonstrated the validity of the EMD method in a BNNT-water system, where the
      slip length is very small compared to that in a CNT pore of similar diameter. The
      developed method enables us to calculate the interfacial friction coefficient
      directly from EMD simulations, while friction can be estimated using NEMD by
      performing simulations at various external driving forces, thereby increasing the
      overall computational time. The EMD analysis revealed a curvature dependence in
      the friction coefficient, which induces the slip length dependency on the tube
      diameter. Conversely, in flat graphene nanopores, both L s and friction
      coefficient show no strong dependency on the channel width.

PMID- 30207540
TI  - Symbolic time series analysis of fNIRS signals in brain development assessment.
AB  - OBJECTIVE: Assessing an infant's brain development remains a challenge for
      neuroscientists and pediatricians despite great technological advances. As a non
      invasive neuroimaging tool, functional near-infrared spectroscopy (fNIRS) has
      great advantages in monitoring an infant's brain activity. To explore the dynamic
      features of hemodynamic changes in infants, in-pattern exponent (IPE), anti
      pattern exponent (APE), as well as permutation cross-mutual information (PCMI)
      based on symbolic dynamics are proposed to measure the phase differences and
      coupling strength in oxyhemoglobin (HbO) and deoxyhemoglobin (Hb) signals from
      fNIRS. APPROACH: First, simulated sinusoidal oscillation signals and four coupled
      nonlinear systems were employed for performance assessments. Hilbert transform
      based measurements of hemoglobin phase oxygenation and deoxygenation (hPod) and
      phase-locking index of hPod (hPodL) were calculated for comparison. Then, the
      IPE, APE and PCMI indices from resting state fNIRS data of preterm, term infants
      and adults were calculated to estimate the phase difference and coupling of HbO
      and Hb. All indices' performance was assessed by the degree of monotonicity
      (DoM). The box plots and coefficients of variation (CV) were employed to assess
      the measurements and robustness in the results. MAIN RESULTS: In the simulation
      analysis, IPE and APE can distinguish the phase difference of two sinusoidal
      oscillation signals. Both hPodL and PCMI can track the strength of two coupled
      nonlinear systems. Compared to hPodL, the PCMI had higher DoM indices in
      measuring the coupling of two nonlinear systems. In the fNIRS data analysis,
      similar to hPod, the IPE and APE can distinguish preterm, term infants, and
      adults in 0.01-0.05 Hz, 0.05-0.1 Hz, and 0.01-0.1 Hz frequency bands,
      respectively. PCMI more effectively distinguished the term and preterm infants
      than hPodL in the 0.05-0.1 Hz frequency band. As symbolic time series measures,
      the IPE and APE were able to detect the brain developmental changes in subjects
      of different ages. PCMI can assess the resting-state HbO and Hb coupling changes
      across different developmental ages, which may reflect the metabolic and
      neurovascular development. SIGNIFICANCE: The symbolic-based methodologies are
      promising measures for fNIRS in estimating the brain development, especially in
      assessing newborns' brain developmental status.

PMID- 30207538
TI  - Remodeling of lumbar motor circuitry remote to a thoracic spinal cord injury
      promotes locomotor recovery.
AB  - Retrogradely-transported neurotrophin signaling plays an important role in
      regulating neural circuit specificity. Here we investigated whether targeted
      delivery of neurotrophin-3 (NT-3) to lumbar motoneurons (MNs) caudal to a
      thoracic (T10) contusive spinal cord injury (SCI) could modulate dendritic
      patterning and synapse formation of the lumbar MNs. In vitro, Adeno-associated
      virus serotype two overexpressing NT-3 (AAV-NT-3) induced NT-3 expression and
      neurite outgrowth in cultured spinal cord neurons. In vivo, targeted delivery of
      AAV-NT-3 into transiently demyelinated adult mouse sciatic nerves led to the
      retrograde transportation of NT-3 to the lumbar MNs, significantly attenuating
      SCI-induced lumbar MN dendritic atrophy. NT-3 enhanced sprouting and synaptic
      formation of descending serotonergic, dopaminergic, and propriospinal axons on
      lumbar MNs, parallel to improved behavioral recovery. Thus, retrogradely
      transported NT-3 stimulated remodeling of lumbar neural circuitry and synaptic
      connectivity remote to a thoracic SCI, supporting a role for retrograde transport
      of NT-3 as a potential therapeutic strategy for SCI.

PMID- 30207543
TI  - On the sintering of solution-based silver nanoparticle thin-films for sprayed and
      flexible antennas.
AB  - In this work, we report on the fabrication and characterization of sub-300 nm
      electrode films based on solution-processed silver nanoparticles (AgNPs).
      Following the deposition of the electrode material using a scalable and
      homogenous spray process, the films are treated with thermal or photonic
      sintering to promote the coalescence of the nanoparticles and in turn decrease
      the resistivity of the films. After sintering, a resistivity of 63 +/- 13 nOmega
      m is achieved for the AgNP films, which is only by a factor of four larger than
      the literature value for bulk silver. Both post-deposition treatments show a
      similar performance with regard to the achieved resistivity. However, photonic
      sintering avoids the need for thermal annealing at substrate temperatures of 150 
      degrees C and above. In addition, the photonic sintering process can easily be
      embedded in a roll-to-roll process and is extremely fast with light exposure
      times below 3 ms. Thus, this manufacturing technique paves the way for the use of
      flexible substrates in electronics. As a simple and practical application, we
      present the use of AgNP films for antennas operating in the 5 GHz band on
      flexible polyethylene terephthalate substrate. An original coplanar design is
      employed for the fabrication of antennas with a single conductive layer that
      exhibit a maximum return loss and radiation of -27 dB and 95%, respectively.

PMID- 30207544
TI  - Synthesis of urchin-like Co3O4 spheres for application in oxygen evolution
      reaction.
AB  - For oxygen evolution electrocatalysis of water splitting, unique urchin-shaped
      Co3O4 spheres were successfully grown on nickel foam by hydrothermal synthesis of
      Co(OH)F precursor and subsequent annealing method. The formation process was
      investigated by the evolution of phase structure and morphology with hydrothermal
      reaction time. And it can be explained by a 'disks-flowers-urchins' mechanism.
      Moreover, the Co3O4 urchins/NF exhibits considerable catalytic properties. It
      shows a low overpotential of 308 mV at a current density of 20 mA cm-2 in
      alkaline solution. In the meantime, such material has a small Tafel slope of 82.1
      mV dec-1, large electrochemical active surface area and good long-term stability.
      The obvious promotion of oxygen evolution reaction performance can be attributed
      to the special morphology and the direct attachment to the substrate, which
      improve the exposed active sites, lower the internal resistance and accelerate
      the charge transport. Thus, the Co3O4 urchins/NF not only has a great potential
      promising behavior, but also provides the basis for subsequent performance
      improvement.

PMID- 30207545
TI  - Correlations among morphology, composition, and photoelectrochemical water
      splitting properties of InGaN nanorods grown by molecular beam epitaxy.
AB  - The mechanism underlying the effect of growth condition on the morphology
      evolution of InGaN nanorods (NRs) has been systematically investigated. The
      increased Ga flux enhances both the axial and the radial growth at the growth
      stage. However, the changed Ga flux influences not only the growth but also the
      nucleation of InGaN NRs. At the nucleation stage, the increased Ga flux shortens
      the delay time for NR formation, and prolongs the growth stage for a fixed total
      growth time. Those two aspects result in the increase of NR diameter and height
      with the supplied Ga flux. In addition, the continuous nucleation is ended much
      earlier due to the accelerated saturation of substrate area with the increased Ga
      flux, resulting in a decreased final NR density. In addition to the morphology
      evolution with the Ga flux, the composition characteristic of InGaN NRs has been
      also studied. The In distribution of InGaN NRs depends critically on the NR
      diameter along the NR growth direction, and the NRs show a morphology-dependent
      In incorporation. Interestingly, the InGaN NRs discussed here show a radial Stark
      effect induced by the pinned Fermi level. The radial Stark effect shifts the
      absorption edge of the InGaN NRs toward longer wavelengths, makes the InGaN NRs
      attractive for photoelectrochemical water splitting applications. The
      photoelectrochemical measurements present a significant increase in the
      photocurrent with the increased total surface area of the InGaN NRs, which is due
      to the enhanced light absorption effects and the enlarged interfacial area of the
      semiconductor/electrolyte.

PMID- 30207546
TI  - Sub-5 nm monolayer black phosphorene tunneling transistors.
AB  - The successful fabrication of sub-5 nm 2D MoS2 field-effect transistors (FETs)
      announces the approaching post-silicon era. It is possible for tunneling field
      effect transistors (TFETs) based on monolayer black phosphorene (ML BP) to work
      well in the sub-5 nm region because of its moderate direct band gap, anisotropic
      electronic properties and high carrier mobility. We simulate the device
      performance limit of the ML BP TFETs at the sub-5 nm scale using ab initio
      quantum transport calculations. We predict that the on-state currents (I on) of
      the sub-5 nm ML BP TFETs will exceed those of the ML WTe2 TFETs, which possess
      the highest I on among the transition-metal dichalcogenide family. In particular,
      the I on of the ML BP TFETs can fulfill the 2028 requirements of the
      international technology roadmap for semiconductors (ITRS) for the high
      performance (HP) devices until the gate length is scaled down to 4 nm, while the
      delay times and power dissipations always surpass the 2028 requirements of the
      ITRS HP devices significantly in the whole sub-5 nm region.

PMID- 30207547
TI  - Tunable high Q-factor terahertz complementary graphene metamaterial.
AB  - Based on the complementary graphene asymmetric double bars patterns, the tunable
      Fano resonances with large Q-factors have been investigated in the terahertz
      regime, including the effects of Fermi levels, structural parameters and
      operation frequency. The results reveal that compared with existed graphene
      tunable devices, the Fano resonant curve is very narrow and indicates a large Q
      factor of about 60. The strong Fano resonant curves can be convenient tailored.
      As Fermi level increases, the amplitude of the Fano dip decreases, and the
      resonant peak position shifts to high frequency. The amplitude modulation depth
      (MD) of the Fano curve is more, about 90%, if the Fermi level changes in the
      scope of 0.2-1.0 eV. With the increase of the sample refractive index, the
      resonant Fano dip shifts low frequency, and the dip amplitude MD can reach more
      than 40%. The results are very helpful to understand the tunable mechanisms of
      graphene based Fano systems and to design high sensitivity functional devices,
      e.g. sensors, modulators, and antenna.

PMID- 30207548
TI  - Controllable epitaxial growth of MoSe2-MoS2 lateral heterostructures with tunable
      electrostatic properties.
AB  - Recently, two-dimensional (2D) transition-metal dichalcogenides (TMDCs) have
      attracted much attention due to their promising applications in the fields of
      electronics and optoelectronics. Controllable growth of TMDC heterostructures
      stimulates new interest by tuning their optical and electronic properties.
      Herein, large-scale lateral MoSe2-MoS2 and MoSe2(1-x)S2x -MoS2 heterostructures
      have been synthesized through one-step epitaxial ambient-pressure chemical vapor
      deposition method and we found that the growth time plays an important role in
      the formation of lateral heterostructures. Lateral MoSe2-MoS2 heterostructures
      have been systematically characterized by using atomic force microscopy, Raman
      spectroscopy and photoluminescence spectroscopy. Corresponding surface potential
      and charge distributions of MoSe2-MoS2 heterostructures have been investigated by
      employing Kelvin probe force microscopy. We found that the electrostatic
      properties of MoSe2-MoS2 heterostructures can be effectively tuned by injecting
      charges through conductive atomic force microscopy. Our results pave a new route
      for constructing 2D lateral heterostructures toward electronic and optoelectronic
      applications.

PMID- 30207549
TI  - Fast long-range charge transfer in quantum dot arrays.
AB  - Charge, spin and quantum states transfer in solid state devices is an important
      issue in quantum information. Adiabatic protocols, such as coherent transfer by
      adiabatic passage have been proposed for direct charge transfer, also denoted as
      long-range transfer, between the outer dots in a QD array without occupying the
      intermediate ones. However adiabatic protocols are prone to decoherence. With the
      aim of achieving direct charge transfer between the outer dots of a QD array with
      high fidelity, we propose a protocol to speed up the adiabatic transfer, in order
      to increase the fidelity of the process. Based on adiabaticity shortcuts, by
      properly engineering the pulses, fast adiabatic-like direct charge transfer
      between the outer dots can be obtained. We also discuss the impact of transfer
      fidelity on the operation time in the presence of dephasing. The proposed
      protocols for accelerating long-range charge and state transfer in a QD array
      offer a robust mechanism for quantum information transfer, by minimizing the
      decoherence and relaxation processes.

PMID- 30207550
TI  - Metabolic acidosis in kidney transplant recipients.
AB  - Introduction Metabolic acidosis (MA) may accelerate the progression of chronic
      kidney disease (CKD) and is an important risk factor for increased mortality in
      CKD patients. The clinical value of MA in kidney transplant (KTx) recipients has
      not been extensively studied so far. Objectives The aim of this clinical single-
      center case--control study was to assess the prevalence of MA in KTx recipients
      in comparison with CKD patients and to identify pathogenic factors for MA in KTx
      recipients. Patients and methods Venous blood concentrations of bicarbonate (HCO3
      ) and blood hemoglobin concentrations were measured in 500 KTx recipients and 500
      CKD patients matched for sex, age, and estimated glomerular filtration rate
      (eGFR). None of these patients received alkali treatment before the study. MA was
      diagnosed in KTx recipients with HCO3- levels lower than 22 mmol/l. Results The
      prevalence of MA was lower in KTx recipients than in CKD patients (12.0% vs
      19.6%; P = 0.001). In both groups, the prevalence increased with progression of
      CKD stages (P <0.001 for trend) and was higher in patients with anemia. In a
      multivariable analysis, hemoglobin concentrations correlated independently with
      eGFR and HCO3- in KTx recipients (beta = 0.314, P <0.001 and beta = 0.274, P
      <0.001, respectively). Similar correlations were observed in CKD patients (beta =
      0.273, P <0.001 and beta = 0.123, P = 0.006, respectively). Conclusions Our study
      revealed that the prevalence of MA is lower in KTx recipients than in CKD
      patients. Moreover, in KTx recipients, blood bicarbonate concentrations are
      related to kidney function and blood hemoglobin concentrations.

PMID- 30207551
TI  - Multivalvular endocarditis.

PMID- 30207552
TI  - Identifying Patients for Nonstatin Therapy.
AB  - Statins are first-line therapy for reducing atherosclerotic cardiovascular
      disease (ASCVD) risk. Some patients remain at high ASCVD risk despite maximizing
      statin therapy. Ezetimibe and proprotein convertase subtilisin/kexin type 9
      (PCSK9) monoclonal antibodies (mAbs) have been shown to reduce ASCVD events in
      randomized trials and may be of benefit in selected high-risk patients with
      cardiovascular disease (CVD) or familial hypercholesterolemia (FH). Number-needed
      to-treat (NNT) to prevent one ASCVD event can help identify groups of patients
      who may gain a net benefit from added nonstatin therapy. Patient groups with NNTs
      <25 (in whom PCSK9 mAbs may approach cost effectiveness with discounting) include
      extremely high-risk patients (those with CVD with FH, polyvascular disease, or
      recurrent ASCVD events) with lowdensity lipoprotein cholesterol (LDL-C) levels
      >=70 mg/dL, very high-risk patients (those with CVD with diabetes [and no
      polyvascular disease], chronic kidney disease, or acute coronary syndromes, or
      CVD or FH with poorly controlled risk factors) with LDL-C levels >=100 mg/dL, and
      high-risk patients (those with CVD or FH with well-controlled risk factors) with
      LDL-C >=130 mg/dL. Ezetimibe, which is generic in the United States, is
      reasonable for patient groups with NNTs <30, the level considered reasonable by
      most patients. This includes extremely high-risk patients with LDL-C levels >=130
      mg/dL, or very high-risk patients with LDL-C >=190 mg/dL. All guidelines
      recommend statin therapy for the prevention of ASCVD.

PMID- 30207553
TI  - Statin Intolerance.
AB  - Statins are critical medications to prevent and treat cardiovascular disease2 and
      they are generally very well tolerated. In some instances, however, statin
      intolerance may limit use of these lifesaving medications. Statin intolerance has
      many definitions but is commonly diagnosed when a patient is unable to continue
      statin therapy due to perceived, or objectively documented, adverse effects. A
      very high rate of discontinuation of statin therapy warrants a closer look at the
      implications from the standpoint of cardiovascular risk in statin-intolerant
      patients, as well as an evaluation of the available options to help patients
      maintain their statin therapy and understand the potential benefits of such
      therapy.

PMID- 30207554
TI  - Can We Cure Atherosclerosis?
AB  - Cardiovascular disease mortality rates have begun to rise in the United States.
      Based on the large body of supportive evidence, we propose a proof-of-concept,
      first-in-human trial to cure atherosclerosis: CURing Early ATHEROsclerosis (CURE
      ATHERO). This trial is based on a model of intensive induction therapy for
      extensive, if not complete, plaque regression, followed by intermittent
      maintenance therapy. An extensive body of evidence has demonstrated the causal
      role of apolipoprotein B lipoproteins in atherosclerosis progression and data
      suggest intensive low-density lipoprotein cholesterol (LDL-C) lowering may have a
      substantial impact on earlier stages of atherosclerosis. Compared with lifetime
      treatment to prevent atherosclerosis progression, this induction-intermittent
      treatment model will minimize costs and maximize adherence and safety.

PMID- 30207555
TI  - Familial Hypercholesterolemia: Although Identification Advances, Appreciation and
      Treatment Lag.
AB  - Familial hypercholesterolemia is one of the most common autosomal dominant
      inherited genetic disorders, yet it is frequently undiagnosed, leading to a
      markedly increased risk for cardiovascular events. Understanding the
      pathophysiology of the disease as well as the importance of cascade screening is
      critical to appropriate treatment of patients. Though the mainstay of therapy for
      heterozygous familial hypercholesterolemia remains statins, many patients require
      additional therapy including ezetimibe and/or proprotein convertase
      subtilisin/kexin type 9 (PCSK9) antibodies to achieve adequate low-density
      lipoprotein cholesterol (LDL-C) lowering. Access to PCSK9 inhibitors remains a
      significant clinical problem.

PMID- 30207557
TI  - Access to PCSK9 Inhibitors.

PMID- 30207556
TI  - PCSK9 Inhibitors: Mechanism of Action, Efficacy, and Safety.
AB  - Low-density lipoprotein (LDL) receptors on the surface of liver hepatocytes are
      the primary way that humans regulate serum LDL cholesterol levels. Proprotein
      convertase subtilisin/kexin type 9 (PCSK9) is a proteolytic enzyme that
      indirectly regulates serum LDL cholesterol (LDL-C) by causing the destruction of
      LDL receptors. Less LDL receptors result in increased LDL-C in the bloodstream
      but inhibiting or binding the circulating PCSK9 results in increased LDL
      receptors with the resultant decrease in serum LDL-C. Two PCSK9 inhibitors are
      currently approved for use: alirocumab and evolocumab. Both are fully human
      monoclonal antibodies that bind free PCSK9. Herein we discuss the mechanism of
      action, efficacy, and safety of PCSK9 inhibitors. clinical problem.

PMID- 30207558
TI  - Clinical Usefulness of Magnetic Resonance Imaging in Four Children With
      Scleroderma.
AB  - Children with localized scleroderma may have more serious sequelae than adults
      with the disease. In this case report, we analyzed four girls with localized
      scleroderma (generalized morphea) to evaluate the clinical usefulness of magnetic
      resonance imaging in facilitating disease control and investigating patient
      responsiveness to various treatments. Two of the children had flexion
      contracture, and two displayed a clear high-intensity area in the bone marrow
      under the sclerotic skin on magnetic resonance imaging. Two girls had different
      bilateral circumferences of the legs or forearms. These abnormalities were
      detected without any obvious changes in blood chemistry. Our results demonstrated
      that magnetic resonance imaging is useful for the evaluation of treatment effects
      for localized scleroderma in children.

PMID- 30207559
TI  - The Assessment of Serum Endocan Levels in Children With Juvenile Idiopathic
      Arthritis.
AB  - Objectives: This study aims to evaluate the levels of serum endocan in children
      with juvenile idiopathic arthritis (JIA). Patients and methods: Sixty-seven
      children with JIA (30 males, 37 females; mean age 10.4+/-4.9 years; range 2 to 18
      years) and a sex- and age- matched healthy control group of 39 children (16
      males, 23 females; mean age 9.3+/-4.1 years; range 1 to 17 years) were recruited.
      Patients with JIA were divided into two groups as the clinically active JIA group
      (n=27) and inactive JIA group (n=40). Results: The median serum endocan level in
      patients with JIA was significantly higher than in the control group (633.75 ng/L
      vs. 379.76 ng/L, p<0.01). Comparison between patients with active JIA and
      inactive JIA was not significant in terms of endocan levels (618.70 ng/L vs.
      687.36 ng/L, p=0.34). There was a weak negative correlation between Childhood
      Health Assessment Questionnaire scores of patients with JIA and serum endocan
      levels. Conclusion: The high level of serum endocan highlighted the endothelial
      damage in patients with JIA.

PMID- 30207560
TI  - Value of Serum Carbohydrate Antigen 19-9 and Carcinoembryonic Antigen in
      Evaluating Severity and Prognosis of Connective Tissue Disease-Associated
      Interstitial Lung Disease.
AB  - Objectives: This study aims to detect serum carcinoembryonic antigen (CEA) and
      carbohydrate antigen 19-9 (CA 19-9) levels in connective tissue disease
      associated interstitial lung disease (CTD-ILD) patients and to demonstrate their
      values in evaluating the severity and prognosis of CTD-ILD. Patients and methods:
      The study included 82 CTD-ILD patients (54 males, 28 females; mean age 67.9
      years; range 29 to 91 years) and 82 controls (54 males, 28 females; mean age 68.1
      years; range 30 to 92 years). Patients were followed-up for 12 months.
      Correlations of serum CEA and CA 19-9 with disease severity parameters (pulmonary
      function, oxygenation index and involvement score on high resolution computed
      tomography) were analyzed. Survival analysis was used to evaluate significance of
      serum CEA and CA 19-9 as prognosis predictors. Results: Serum CEA and CA 19-9
      levels were higher in CTD-ILD patients compared with controls (both p<0.05) and
      correlated with disease severity (p<0.05 for all R2). High levels of serum CEA
      and CA 19-9 were associated with poor survival (both p<0.05). Serum CEA level was
      indicated as a prognostic factor for cumulative survival (hazard ratio=1.685, 95%
      confidence interval: 1.405-2.021, p=0.001). Conclusion: In CTD-ILD patients,
      serum CEA and CA 19-9 are elevated and can be indicators of disease severity.
      Moreover, serum CEA is a significant and independent predictor of survival.

PMID- 30207562
TI  - Tofacitinib Versus Non-Tumor Necrosis Factor Biologics for Patients With Active
      Rheumatoid Arthritis.
AB  - Objectives: This study aims to compare the disease status of patients with active
      rheumatoid arthritis (RA) after treatment with tofacitinib or non- tumor necrosis
      factor (TNF) biologics. Patients and methods: The study included a total of 50 RA
      patients (18 males, 32 females; mean age 68.3+/-1.3 years; range 42 to 92 years).
      We prospectively and randomly enrolled 25 patients for treatment with tofacitinib
      (Tofa group: 10 males, 15 females; mean age 68.3+/-2.0 years; range, 42 to 92
      years) and 25 for treatment with non-TNF biologics (non-TNF group: 8 males, 17
      females; mean age 68.3+/-1.7 years; range 51 to 92 years). Mean disease activity
      score 28 (DAS28), C-reactive protein (CRP), clinical disease activity index
      (CDAI), health assessment questionnaire (HAQ)-disability index (DI), and matrix
      metalloproteinase-3 values were recorded at baseline and at 4, 8, and 12 months.
      Results: There was a significant difference in the percent changes of DAS28, CRP
      and CDAI at every time point versus baseline in both treatment groups. HAQ-DI was
      also significantly different at every time point in both groups except for at
      four months in the non-TNF group. Conclusion: Tofacitinib was well tolerated in
      active RA patients and exerted effects comparable to those of non-TNF biologics.

PMID- 30207561
TI  - Effect of Ozone in Freund's Complete Adjuvant-Induced Arthritis.
AB  - Objectives: This study aims to investigate the effectiveness and reliability of
      ozone (O3) in Freund's complete adjuvant (FCA)-induced arthritis, an animal model
      for rheumatoid arthritis. Patients and methods: Thirty-six four- to five-month
      old male Wistar rats weighing between 274-420 gr were used in this study. Saline
      was injected into the hind paws of half of these rats, and FCA was injected into
      the other half. At the end of two weeks, 40 MUg of O3 was administered to nine
      rats from each group twice a week for seven total doses. The rats were followed
      up in terms of clinical findings. At the sixth week, the rats were sacrificed and
      serum malondialdehyde, glutathione peroxidase, and superoxide dismutase levels
      were measured. In addition, ankle joints were separated for histopathological
      examination. Results: Significant improvement was observed in terms of hind-paw
      diameter, severity of arthritis, and histopathological findings of inflammation
      after O3 treatment in the group with FCA-induced arthritis. Although it was not
      quite significant, an upward trend was detected in oxidative stress markers with
      O3 treatment. Conclusion: This study, the first to investigate the effects of
      systemic O3 on the clinical and histopathological outcomes of rheumatoid
      arthritis, indicates that O3 is a highly effective and reliable treatment method
      in FCA-induced arthritis in animal models.

PMID- 30207563
TI  - Fibromyalgia Syndrome and Vitiligo: A Novel Association.
AB  - Objectives: This study aims to assess the relationship between fibromyalgia
      syndrome (FMS) and vitiligo in Iraqi patients and evaluate the predictors of this
      relationship, if present. Patients and methods: The case-control study included
      100 Iraqi patients (46 males, 54 females; mean age 30.4+/-14 years; range 15 to
      65 years) with vitiligo and 200 age- and sex-matched healthy controls (74 males,
      126 females; mean age 30.3+/-9.4 years; range 15 to 62 years). Baseline
      characteristics of patients and controls were recorded. The 2012 Canadian
      Guidelines criteria were used for the diagnosis of FMS and applied to all
      patients and controls. Results: Prevalence of FMS in vitiligo patients and
      controls was 12% and 7%, respectively (p=0.15, odds ratio=1.8, 95% confidence
      interval=0.8-4.08). FMS symptoms in vitiligo patients were fatigue (46%), diffuse
      body pain (34%), sleep disturbance (33%), cognitive dysfunction (30%), and mood
      disorders (23%), while visceral involvements were central nervous system (52%),
      skin (35%), gastrointestinal tract (32%), cardiovascular system- respiratory
      system (16%), genitourinary tract (8%), and ear nose throat (7%). Of vitiligo
      patients, FMS was significantly more common among females (22.2%) compared to
      none among males (0%) (p<0.05). Prevalence of FMS was restricted to female sex
      only and a significantly higher prevalence rate of FMS was found among female
      vitiligo patients (22.2%) compared to controls (9.5%). Receiving phototherapy
      significantly increased the risk of having FMS by 5 times compared to female
      patients not receiving phototherapy. Use of any steroid reduced the risk of
      having FMS by 2.5 times (inverse of odds ratio=0.4) among females patients
      (p>0/05). No significant association was found between FMS in vitiligo patients
      and age, disease duration, type of vitiligo, use of any immunosuppressant and
      body mass index (p>0.05). Conclusion: Fibromyalgia syndrome was more prevalent in
      vitiligo patients compared to controls, which was clinically important but
      statistically not significant. There was a significant association between FMS in
      vitiligo patients and female sex, severe form of vitiligo, and receiving
      phototherapy. This may suggest that early diagnosis of FMS in vitiligo patients
      may help in early treatment and subsequently improve patients' quality of life.

PMID- 30207565
TI  - Corrigendum.
AB  - [This corrects the article DOI: 10.2217/cnc-2017-0002.].

PMID- 30207564
TI  - Bee Venom and Hesperidin Effectively Mitigate Complete Freund's Adjuvant-Induced
      Arthritis Via Immunomodulation and Enhancement of Antioxidant Defense System.
AB  - Objectives: This study aims to assess the antirheumatic activity of bee venom
      (BV) and/or hesperidin as natural products in complete Freund's adjuvant (CFA)
      induced arthritis in male Wistar rats. Material and methods: Rheumatoid arthritis
      was induced in 30 male Wistar rats (weight 130 g to 150 g; age 10 to 12 weeks) by
      subcutaneous injection of CFA into the right hind paw of the rats. The rats were
      divided into five groups of six rats in each and administered the following
      regimens for 21 days: Normal group (given the equivalent volume of saline and
      carboxymethylcellulose), arthritic group (given the equivalent volume of saline
      and carboxymethylcellulose), arthritic group treated with BV (treated with BV
      along with carboxymethylcellulose), arthritic group treated with hesperidin
      (treated with hesperidin along with saline), and arthritic group treated with BV
      and hesperidin (treated with BV and hesperidin concurrently). Results: Bee venom
      and/or hesperidin successfully reversed the CFA-arthritis-induced increases in
      right hind leg paw swelling, leukocytes' count, liver lipid peroxidation, serum
      inflammatory cytokine interleukin (IL-2 and IL-12) levels and spleen tumor
      necrosis factor-alpha messenger ribonucleic acid expression. Moreover, the CFA
      induced down-regulation in serum IL-10 level and spleen IL-4 messenger
      ribonucleic acid expression as well as the deterioration in the antioxidant
      defense system were significantly improved as a result of BV and hesperidin
      administration. Both treatments also markedly counteracted the severe
      inflammatory changes and leukocytic infiltration in the periarticular tissue of
      the ankle joints. In addition, BV and hesperidin obviously amended the lymphoid
      hyperplasia in white pulps of spleen as well as the widening of the medulla and
      mononuclear cell infiltration found in thymus. Conclusion: Bee venom and
      hesperidin administration produced their ameliorative effects on rheumatoid
      arthritis via their antioxidant, antiinflammatory and immunomodulatory
      potentials. BV plus hesperidin particularly seemed to be the most potent in
      improving rheumatoid arthritis in Wistar rats.

PMID- 30207566
TI  - Systemic Lupus Erythematosus Induced by Autoimmune/ Inflammatory Syndrome Induced
      by Adjuvants. Is it Possible? Long-Term Follow-up and Literature Review.

PMID- 30207567
TI  - Effects of Glycation on Mechanical Properties of Articular Cartilage.

PMID- 30207569
TI  - Evaluation of Ventricular Diastolic Function in Patients With Fibromyalgia
      Syndrome.
AB  - Objectives: This study aims to compare the diastolic functions between
      fibromyalgia (FM) patients and control subjects by using transthoracic
      echocardiography. Patients and methods: This case-control and cross-sectional
      study included 34 female FM patients (mean age 43.6+/-8.2 years; range 28 to 57
      years), who were diagnosed by The American College of Rheumatology 1990 Criteria
      for the Classification of Fibromyalgia and defined as the FM group. A control
      group was defined consisting of 30 healthy females (mean age 41.2+/-9.1 years;
      range 22 to 54 years). Echocardiography findings of the groups were compared.
      Results: The body mass index and mean disease duration of the FM group were
      25.37+/-2.71 kg/m2 and 12.24 months, respectively. The body mass index of the
      control group was 25.58+/-1.49 kg/m2. There was no significant difference between
      the groups in terms of age and body mass index. Isovolumetric relaxation time and
      mitral E-wave deceleration time values were significantly higher in the FM group
      than in the control group (p=0.047, p=0.003, respectively). Conclusion:
      Isovolumetric relaxation time and mitral valve deceleration time are
      significantly prolonged in FM patients compared with healthy subjects. Female
      patients with FM seem to be under risk of impaired relaxation and diastolic
      function of the left ventricle.

PMID- 30207568
TI  - Prevalence of Rheumatoid Arthritis and Spondyloarthritis in Turkey: A Nationwide
      Study.
AB  - Objectives: This study aims to estimate the prevalence of rheumatoid arthritis
      (RA) and spondyloarthritis (SpA) in Turkey using the same telephone questionnaire
      developed for screening RA and SpA in France and used in Serbia and Lithuania.
      Material and methods: The study was performed in two steps. In step I, the French
      questionnaire was translated into Turkish and validated through a group of 200
      patients (80 males, 120 females; mean age 44.0+/-13.1 years; range 19 to 75
      years) followed up at the rheumatology departments of University Hospitals in
      Antalya and Ankara. In step II, the validated Turkish questionnaire was
      administered face-to-face to randomly selected 4,012 subjects (1,670 males, 2,342
      females; mean age 41.5+/-16.8 years; range 16 to 97 years) by trained general
      practitioners across the country, in 25 prov- inces for case detection. The
      subjects who were suspected of having RA or SpA in accordance with the
      questionnaire were invited to the nearest university hospital for rheumatologic
      examination in order to confirm the diagnosis. Results: In step II, a total of 25
      subjects (2 males, 23 females) were diagnosed as RA. The standardized RA
      prevalence for the general population of Turkey was calculated as 0.56% (95%
      confidence interval [CI]; 0.33-0.79), 0.10% (95% CI; -0.05-0.25) for males and
      0.89% (95% CI; 0.51-1.27) for females. A total of 18 subjects (3 males, 15
      females) were diagnosed as SpA. The standardized SpA prevalence for the general
      population of Turkey was 0.46% (95% CI; 0.25-0.67), 0.17% (95% CI; -0.03-0.37)
      for males and 0.65% (95% CI; 0.32-0.98) for females. The prevalence of RA was
      highest in the Northern region (2.00%) and the prevalence of SpA was highest in
      the Central region (1.49%). Conclusion: The prevalences of RA and SpA in Turkey
      are close to each other and there are significant inter-regional variations in
      prevalences of both RA and SpA.

PMID- 30207570
TI  - Multiple Eruptive Dermatofibromas in a Patient With Systemic Lupus Erythematosus
      Treated With Methylprednisolone.

PMID- 30207572
TI  - Successful Treatment of Concurrent Mucormycosis and Diffuse Alveolar Hemorrhage
      in a Patient With Newly Diagnosed Systemic Lupus Erythematosus.

PMID- 30207571
TI  - The Validity and Reliability of Turkish Version of the Jenkins Sleep Evaluation
      Scale in Rheumatoid Arthritis.
AB  - Objectives: This study aims to assess the validity and reliability of the Jenkins
      Sleep Evaluation Scale (JSS) when applied to a Turkish population with rheumatoid
      arthritis. Patients and methods: The Turkish version of JSS (JSS-TR) was obtained
      after translation from English into Turkish, according to standard guidelines.
      The study included 61 patients of rheumatoid arthritis (13 males, 48 females;
      mean age 50.5 years; range 19 to 72 years) as defined by the American College of
      Rheumatology 2010 criteria. The internal consistency (Cronbach's alpha) was
      assessed for reliability. Content and construct validity (convergent and
      divergent validities) were evaluated. The relationships between the JSS-TR and
      the Pittsburgh Sleep Quality Index, the Multidimensional Assessment of Fatigue
      scale, subgroups of the Nottingham Health Profile, and the Stanford Health
      Assessment Questionnaire were assessed for convergent validity. In addition, the
      relationships between the JSS-TR and age, disease duration, visual analog scale
      patient global score, and disease activity score 28 were assessed for divergent
      validity. Results: The Cronbach's alpha of JSS-TR was 0.80. All questions and the
      answer choices for the scale were understood well and related to some dimension
      of sleep demonstrating good content validity. The JSS-TR had good correlations
      with functional parameters (which are convergent), and poor or insignificant
      correlations with non-functional parameters (which are divergent). This implies
      that the JSS-TR had good construct validity in the context of this study.
      Overall, the JSS-TR had the best correlation with the Pittsburgh Sleep Quality
      Index (Spearman's rank correlation coefficient=0.76). Conclusion: The JSS-TR is a
      valid and reliable instrument. It is a simple and effective tool which can be
      used to evaluate sleep disturbances in rheumatoid arthritis patients in both
      daily practice and clinical research.

PMID- 30207573
TI  - Greetings From the Editor.

PMID- 30207574
TI  - Ptosis and Mass Like Lesions in Behcet's Disease: A Rare Presentation.
AB  - In this article, we describe a case of neuro-Behcet's disease presenting with
      unilateral ptosis and facial paresis due to an intracranial mass lesion. A 25
      year-old male patient with a history of Behcet's disease presented with headache,
      vertigo, double vision, ptosis in his right eyelid and slurred speech. Cranial
      magnetic resonance imaging scan revealed a right-sided capsulothalamic lesion,
      which was extending to the right cerebral pedicle, pons and superior cerebellar
      pedicle. This lesion was interpreted as neuro-Behcet's disease involvement of
      central nervous system. Cerebral mass- like lesion is a rare form of neuro
      Behcet's disease. Review of the literature revealed a limited number of cases.
      Ptosis related with Behcet's disease is also a very rare presentation. This case
      shows that this symptom might be a part of the clinical presentation of neuro
      Behcet's disease.

PMID- 30207575
TI  - Passive Smoking is Responsible for Disease Activity in Female Patients With
      Rheumatoid Arthritis.
AB  - Objectives: This study aims to evaluate the effects of passive smoking on disease
      activity in female patients with rheumatoid arthritis (RA). Patients and methods:
      Among a total of 191 female patients with RA (mean age 59.1+/-12.5 years; range
      21 to 87 years) consecutively recruited, 100 female patients (mean age 56.1+/
      13.4 years; range 21 to 87 years) completed the study with mean 17.3 months of
      follow-up. Patients were classified according to smoking status: current, never,
      passive, or ex-smoker. Clinical response between never and passive smokers was
      assessed by disease- activity score 28 (DAS28)-erythrocyte sedimentation rate
      (ESR) and C-reactive protein (CRP) (DAS28-ESR and DAS28-CRP) and by the European
      League Against Rheumatism response criteria. Results: Among the 100 female RA
      patients analyzed, the distribution of smoking status was as follows: current
      (n=3), never (n=55), passive (n=34), and ex-smokers (n=8). There was no
      difference of DAS28-ESR and DAS28-CRP between never and passive smokers at
      baseline. At the time of follow-up, the values of DAS28-ESR and DAS28-CRP in
      never smokers were significantly decreased than those in passive smokers (p=0.019
      and p=0.023, respectively). Patients who never smoked showed a trend to have good
      or moderate European League Against Rheumatism response without statistical
      significance, compared to passive smokers (52.7% vs. 32.4%, respectively;
      p=0.060). Conclusion: This preliminary study implicates that passive smoking
      might be responsible for higher disease activity in female RA patients and never
      smoking might induce good clinical response in RA.

PMID- 30207577
TI  - Association of Anti-Ro/Sjogren's syndrome type A Antibodies and Complete
      Atrioventricular Block in an Adult With Sjogren's Syndrome.
AB  - A 57-year-old female patient with underlying hypertension, dyslipidemia,
      membranous glomerulonephritis, and Sjogren's syndrome presented to our clinic
      with near-syncope and dizziness symptoms. We detected non-conducted sinus beat in
      12-lead electrocardiography. An echocardiography showed that the left ventricular
      systolic function was preserved without a regional wall abnormality. The patient
      did not have symptoms of congestive heart failure or recent myocardial
      infarction. We observed complete atrioventricular block with longest pause of 6.2
      seconds in a 24-hour Holter electrocardiography, and subsequently implanted a
      permanent pacemaker. Anti-Ro/Sjogren's syndrome type A antibodies are commonly
      seen in Sjogren's syndrome and associated with a neonatal complete heart block.
      The pathogenesis of anti-Ro/Sjogren's syndrome type A antibodies in the
      conduction system of an adult heart is still uncertain. In this article, we
      report Sjogren's syndrome in an adult patient with complete atrioventricular
      block and membranous glomerulonephritis, which may be associated with a positive
      titer of anti-Ro/Sjogren's syndrome type A antibodies.

PMID- 30207578
TI  - Evaluation of Impact of Interferon-Induced Helicase C Domain-Containing Protein 1
      Gene in Egyptian Systemic Lupus Erythematosus Patients and its Relationship With
      Vascular Manifestations of the Disease.
AB  - Objectives: This study aims to investigate the impact of interferon-induced
      helicase C domain-containing protein 1 (IFIH1) gene single nucleotide
      polymorphism on interferon pathway signaling in systemic lupus erythematosus
      (SLE) patients specifically with vascular affection. Patients and methods: The
      cross-sectional study included 30 consecutive SLE patients (2 males, 28 females;
      mean age 28+/-3.4 years; range 16 to 40 years) diagnosed according to the
      American College of Rheumatology revised criteria and 10 healthy age- and sex
      matched controls (2 males, 8 females; mean age 27+/-2.5 years; range 22 to 23
      years). SLE patients and controls were compared in terms of quantitative reverse
      transcriptase polymerase chain reaction gene expression of IFIH1 gene, von
      Willebrand factor, carotid intima-media thickness, and ankle brachial index.
      Results: Interferon-induced helicase C domain-containing protein 1 gene
      expression was significantly higher in SLE patients than controls (1.7+/-0.6 and
      0.5+/-0.2, respectively) (p<0.0001). IFIH1 gene expression was highly related to
      vascular complication with a cutoff point at 1.74 and it positively correlated
      with other endothelial dysfunction markers. Conclusion: Interferon-induced
      helicase C domain-containing protein 1 gene (single nucleotide polymorphism
      1990670) is associated with SLE in Egyptian patients. Expression of IFIH1 gene is
      related to disease activity and may serve as a novel predictor of vascular
      affection in SLE.

PMID- 30207579
TI  - A Case of Kawasaki Disease With Severe Lip and Oral Mucosa Involvement
      Complicated With Microstomia and Corrected With Surgery.

PMID- 30207580
TI  - Association of the Commitments and Responsibilities of the Caregiver Within the
      Family to the Disease Activity in Patients With Rheumatoid Arthritis: A Report
      From Turkey.
AB  - Objectives: This study aims to investigate the commitments and responsibilities
      of the family caregiver of rheumatoid arthritis patients and determine the
      association of these to the disease activity. Patients and methods: The study
      included a total of 240 subjects, consisting of 60 rheumatoid arthritis patients
      (8 males, 52 females; mean age 50.4+/-11.1 years; range 25 to 76 years) with
      their respective 60 primary caregivers (42 males, 18 females; mean age 43.1+/
      15.3 years; range 12 to 77 years) and 60 OA patients (7 males, 53 females; mean
      age 62.8+/-9.0 years; range 45 to 85 years) with their respective 60 primary
      caregivers (38 males, 22 females; mean age 47.6+/-13.2 years; range 27 to 87
      years). Disease severity and pain of patients were assessed through visual analog
      scale. Sedimentation and C-reactive protein values were recorded during routine
      visits. Patients were stratified by disease activity that was determined by
      disease activity score-28. Caregivers of patients evaluated disease severity and
      pain by visual analog scale, and completed Caregiver Reaction Assessment (CRA)
      and Caregiver Strain Index questionnaires. For a more objective assessment, tasks
      related to care, household, and assistance and allocated time periods for each
      group of tasks were queried. Results: When CRA and Caregiver Strain Index were
      compared in terms of disease activity, patients significantly differed in impact
      on schedule subscale of CRA (p<0.05). Similarly, disease activity was
      significantly associated with impact on finance subscale of CRA (p<0.05). Impact
      on health subscale of CRA was also correlated with disease activity; i.e., the
      higher the disease activity score-28, the more negative impact on health of the
      caregiver. Conclusion: Patient care is an important part of rheumatoid arthritis
      management. Chronic diseases form commitment on patient's caregiver. That the
      care of the patient may be associated with many factors related to both the
      patient and the caregiver should not be underestimated. We suggest that
      caregiver's strain may be correlated with disease activity.

PMID- 30207586
TI  - Relationship Between Brain Amyloid Deposition and Instrumental Activities of
      Daily Living in Older Adults: A Longitudinal Study from the Multidomain Alzheimer
      Prevention Trial.
AB  - OBJECTIVES: To examine the evolution of instrumental activity of daily living
      (IADL) performance according to the presence of brain amyloid deposition. DESIGN:
      Longitudinal analysis of a randomized controlled trial. SETTING: Neuroimaging
      ancillary study from the Multidomain Alzheimer Prevention Trial (MAPT).
      PARTICIPANTS: Community-dwelling individuals aged 70 and older without dementia
      (N = 269; 60% female, mean age 75+/-4). MEASUREMENTS: Linear mixed models were
      used to assess the 36-month evolution of the performance of an IADL questionnaire
      for primary prevention studies in dementia, the Activity of Daily Living
      Prevention Instrument (ADL-PI), according to the presence of amyloid deposition
      using florbetapir positron emission tomography (PET) (standardized uptake
      value>=1.17). Additional analyses were also conducted to examine the changes in
      specific domains of daily functioning with and without adjustment for age, sex,
      apolipoprotein E, randomization group, and time between baseline and PET
      examination. RESULTS: One hundred two (37.9%) participants were amyloid positive.
      Amyloid-negative participants had statistically significant improvement in ADL-PI
      total score between baseline and 36 months (p=.04). The difference after 3 years
      between amyloid-positive and -negative participants was not significant (beta=
      0.95+/-0.53 at 36 months, p=.08; adjusted models: beta=-1.07+/-0.56, p=.06).
      Amyloid-negative participants also improved in memory-related IADLs (p<.001)
      throughout the study, unlike amyloid-positive participants. CONCLUSION: Amyloid
      positive and -negative older adults are likely to have different trajectories in
      IADL performance. Future research is needed to better understand the relationship
      between amyloid plaques and functional limitations.

PMID- 30207576
TI  - Management of Psoriatic Arthritis: Turkish League Against Rheumatism (TLAR)
      Expert Opinions.
AB  - Objectives: This study aims to establish the first national treatment
      recommendations by the Turkish League Against Rheumatism (TLAR) for psoriatic
      arthritis (PsA) based on the current evidence. Patients and methods: A systematic
      literature review was performed regarding the management of PsA. The TLAR expert
      committee consisted of 13 rheumatologists and 12 physical medicine and
      rehabilitation specialists experienced in the treatment and care of patients with
      PsA from 22 centers. The TLAR recommendations were built on those of European
      League Against Rheumatism (EULAR) 2015. Levels of evidence and agreement were
      determined. Results: Recommendations included five overarching principles and 13
      recommendations covering therapies for PsA, particularly focusing on
      musculoskeletal involvement. Level of agreement was greater than eight for each
      item. Conclusion: This is the first paper that summarizes the recommendations of
      TLAR as regards the treatment of PsA. We believe that this paper provides Turkish
      physicians dealing with PsA patients a practical guide in their routine clinical
      practice.

PMID- 30207587
TI  - Granulocyte-macrophage colony-stimulating factor (GM-CSF) as a therapeutic target
      in psoriasis: randomized, controlled investigation using namilumab, a specific
      human anti-GM-CSF monoclonal antibody.
AB  - BACKGROUND: The relevance of granulocyte-macrophage colony-stimulating factor (GM
      CSF) in the management of psoriasis has not been studied previously. GM-CSF is
      important in the initiation and maintenance of chronic inflammatory processes.
      OBJECTIVES: To investigate the clinical use of GM-CSF neutralization by
      evaluating the efficacy and safety of namilumab (AMG203), a monoclonal antibody
      GM-CSF inhibitor, in patients with moderate-to-severe plaque psoriasis. METHODS:
      A phase II, multicentre, randomized, double-blind, placebo-controlled, parallel
      group, dose-finding, proof-of-concept study (NEPTUNE) was conducted. Four doses
      of namilumab (20, 50, 80 and 150 mg, via subcutaneous injection) were compared
      with placebo. Assessment of the primary end point - the proportion of patients
      achieving >= 75% reduction in Psoriasis Area and Severity Index (PASI 75
      treatment response) - was performed at week 12. Exploratory investigation at the
      tissue level was conducted in a subset of the overall study population. The trial
      was registered with the number NCT02129777. RESULTS: In total, 122 patients were
      enrolled and 106 (86.9%) completed the double-blind treatment; 16 (13.1%)
      prematurely discontinued study medication. Serum concentration-time profiles were
      as expected for subcutaneous delivery of an IgG1 monoclonal antibody, and
      exposure increased proportionally with dose elevation. The number of patients
      showing PASI 75 treatment response at week 12 was low in all groups; no
      significant difference was recorded in this end point between placebo and any
      namilumab group. Similar outcomes were recorded for other clinical study end
      points. Moreover, no significant treatment-related changes from baseline were
      observed in laboratory investigations of cell types or subpopulations, or
      cytokines relevant to inflammatory pathways in psoriasis. CONCLUSIONS: GM-CSF
      blockade is not critical for suppression of key inflammatory pathways underlying
      psoriasis.

PMID- 30207588
TI  - Psychometric validation of the identity abuse scale among LGBTQ individuals.
AB  - Identity abuse (IA) comprises a set of abuse tactics that exploit discriminatory
      systems including homophobia, biphobia, and transphobia (Tesch & Berkerian,
      2015). This study examined the factorial validity of the IA Scale (Woulfe &
      Goodman, 2018) with a large independent sample of lesbian, gay, bisexual,
      transgender, and queer (LGBTQ) individuals. Participants included 1,049 LGBTQ
      identified participants (Mage  = 27.3, 71.9% White, 52.6% cisgender women, and
      18.7% as other nonheterosexual identity in their sexual orientation), recruited
      through listservs. Participants completed an online survey measuring past-year
      and adult exposure to identity, physical, and psychological abuse. Confirmatory
      factor analysis indicated that the measurement model had good fit to the data,
      and strong factor loadings were found across the seven items, confirming a
      unidimensional factor structure. Findings demonstrate the IA Scale's validity and
      reliability, supporting its use to assess the frequency of IA tactics experienced
      within intimate partnerships among LGBTQ individuals.

PMID- 30207589
TI  - Variation in daily ultraviolet radiation exposure and sun protection behaviours
      of melanoma survivors: an observational single-arm pilot study with a wearable
      sensor.

PMID- 30207591
TI  - Children's Experiences of Bullying Victimization and the Influence on Their
      Subjective Well-Being: A Multinational Comparison.
AB  - The study used data from the second wave of the Children's Worlds Survey to
      explore the relation between children's experiences of bullying victimization
      (physical and psychological) and their subjective well-being (SWB) across three
      age groups (8, 10, and 12) and 15 global geographical regions. The sample
      consists of 47,029 children randomly selected from 15 countries. Data were
      analyzed using structural equation modeling and multigroup confirmatory factor
      analysis. The results show appropriate fit structure for the overall model, and
      that the combined influence of physical and psychological bullying made a
      significant contribution to SWB across age groups and geographical regions. The
      findings are interpreted using Cummins's (1995) Homeostasis Theory of SWB.

PMID- 30207590
TI  - Pediatric melanoma in melanoma-prone families.
AB  - BACKGROUND: In the United States, only approximately 0.4% of all melanomas are
      diagnosed in patients aged <20 years. To the authors' knowledge, melanoma in
      pediatric members of melanoma-prone families has not been fully investigated to
      date. The objective of the current study was to evaluate pediatric patients with
      melanoma with extensive follow-up in melanoma-prone families with and without
      cyclin-dependent kinase inhibitor 2A (CDKN2A) mutations. METHODS: For this non
      population-based study, families were followed prospectively for up to 40 years.
      A total of 60 families with >= 3 patients with melanoma were included for
      analysis: 30 CDKN2A mutation-positive (CDKN2A+) and 30 CDKN2A mutation-negative
      (CDKN2A-) families. Age at the time of first melanoma and number of melanomas
      were obtained for each patient and summarized by family or sets (CDKN2A + vs
      CDKN2A-). For set comparisons and categorical variables (occurrence of melanoma
      in pediatric patients, number of melanomas, number of patients with single or
      multiple melanomas), the Pearson chi-square or Fisher exact test was used.
      RESULTS: Regardless of CDKN2A status, melanoma-prone families were found to have
      6-fold to 28-fold higher percentages of patients with pediatric melanoma compared
      with the general population of patients with melanoma in the United States.
      Within CDKN2A + families, pediatric patients with melanoma were significantly
      more likely to have multiple melanomas compared with their relatives who were
      diagnosed at age >20 years (71% vs 38%, respectively; P = .004). CDKN2A +
      families had significantly higher percentages of pediatric patients with melanoma
      compared with CDKN2A- families (11.1% vs 2.5%; P = .004). CONCLUSIONS: These
      observations have implications for the prevention of melanoma as well as clinical
      care for its early detection. Children in melanoma-prone families should have
      careful sun protection from an early age and skin surveillance to reduce their
      risk of melanoma.

PMID- 30207592
TI  - An exploration of posttraumatic growth, loneliness, depression, resilience, and
      social capital among survivors of Hurricane Katrina and the Deepwater Horizon Oil
      Spill.
AB  - The aim of this study was to examine the relationships among posttraumatic growth
      (PTG), loneliness, depression, psychological resilience, and social capital among
      survivors of Hurricane Katrina in 2005 and the Deepwater Horizon oil spill in
      2010. The survey was administered to a spatially stratified, random sample of
      households in the three coastal counties of Mississippi. A total of 216
      participants were included in this study who lived in close proximity to the Gulf
      of Mexico coastline during both disasters. Results from structural equation
      modeling analyses indicated that there was a significant and inverse relationship
      between PTG and loneliness. Conversely, a direct relationship was not found
      between PTG and depressive symptoms; instead, the results revealed an indirect
      relationship between PTG and depressive symptoms through loneliness. Social
      capital was related to loneliness only indirectly through PTG, while
      psychological resilience was related to loneliness both directly and indirectly
      through PTG. Understanding the relationships among these factors, particularly
      the importance of PTG, can provide insight into the long-term adaptation among
      those who have survived multiple disasters. Further, these findings may lead to
      nuanced methods for behavioral health practitioners in assessing and treating
      individuals with symptoms of depression in disaster-prone communities.

PMID- 30207593
TI  - Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality
      worldwide for 36 cancers in 185 countries.
AB  - This article provides a status report on the global burden of cancer worldwide
      using the GLOBOCAN 2018 estimates of cancer incidence and mortality produced by
      the International Agency for Research on Cancer, with a focus on geographic
      variability across 20 world regions. There will be an estimated 18.1 million new
      cancer cases (17.0 million excluding nonmelanoma skin cancer) and 9.6 million
      cancer deaths (9.5 million excluding nonmelanoma skin cancer) in 2018. In both
      sexes combined, lung cancer is the most commonly diagnosed cancer (11.6% of the
      total cases) and the leading cause of cancer death (18.4% of the total cancer
      deaths), closely followed by female breast cancer (11.6%), prostate cancer
      (7.1%), and colorectal cancer (6.1%) for incidence and colorectal cancer (9.2%),
      stomach cancer (8.2%), and liver cancer (8.2%) for mortality. Lung cancer is the
      most frequent cancer and the leading cause of cancer death among males, followed
      by prostate and colorectal cancer (for incidence) and liver and stomach cancer
      (for mortality). Among females, breast cancer is the most commonly diagnosed
      cancer and the leading cause of cancer death, followed by colorectal and lung
      cancer (for incidence), and vice versa (for mortality); cervical cancer ranks
      fourth for both incidence and mortality. The most frequently diagnosed cancer and
      the leading cause of cancer death, however, substantially vary across countries
      and within each country depending on the degree of economic development and
      associated social and life style factors. It is noteworthy that high-quality
      cancer registry data, the basis for planning and implementing evidence-based
      cancer control programs, are not available in most low- and middle-income
      countries. The Global Initiative for Cancer Registry Development is an
      international partnership that supports better estimation, as well as the
      collection and use of local data, to prioritize and evaluate national cancer
      control efforts. CA: A Cancer Journal for Clinicians 2018;0:1-31. (c) 2018
      American Cancer Society.

PMID- 30207594
TI  - Diagnostic accuracy of content-based dermatoscopic image retrieval with deep
      classification features.
AB  - BACKGROUND: Automated classification of medical images through neural networks
      can reach high accuracy rates but lacks interpretability. OBJECTIVES: To compare
      the diagnostic accuracy obtained by using content-based image retrieval (CBIR) to
      retrieve visually similar dermatoscopic images with corresponding disease labels
      against predictions made by a neural network. METHODS: A neural network was
      trained to predict disease classes on dermatoscopic images from three
      retrospectively collected image datasets containing 888, 2750 and 16 691 images,
      respectively. Diagnosis predictions were made based on the most commonly
      occurring diagnosis in visually similar images, or based on the top-1 class
      prediction of the softmax output from the network. Outcome measures were area
      under the receiver operating characteristic curve (AUC) for predicting a
      malignant lesion, multiclass-accuracy and mean average precision (mAP), measured
      on unseen test images of the corresponding dataset. RESULTS: In all three
      datasets the skin cancer predictions from CBIR (evaluating the 16 most similar
      images) showed AUC values similar to softmax predictions (0.842, 0.806 and 0.852
      vs. 0.830, 0.810 and 0.847, respectively; P > 0.99 for all). Similarly, the
      multiclass-accuracy of CBIR was comparable with softmax predictions. Compared
      with softmax predictions, networks trained for detecting only three classes
      performed better on a dataset with eight classes when using CBIR (mAP 0.184 vs.
      0.368 and 0.198 vs. 0.403, respectively). CONCLUSIONS: Presenting visually
      similar images based on features from a neural network shows comparable accuracy
      with the softmax probability-based diagnoses of convolutional neural networks.
      CBIR may be more helpful than a softmax classifier in improving diagnostic
      accuracy of clinicians in a routine clinical setting.

PMID- 30207596
TI  - Older Adults with Cognitive Impairment Have Sex: More Evidence Against the
      Medical Myth of Sexless Aging.

PMID- 30207595
TI  - Proteomic analysis of human T cell-derived exosomes reveals differential RAS/MAPK
      signaling.
AB  - Exosomes are cell-derived vesicles that have been implicated in the pathogenesis
      of many inflammatory diseases. More specifically, it has been shown that T cell
      derived exosomes can induce immunological responses; however, little is known
      about the mechanism and the molecular content of these vesicles. Here, we used a
      proteomic approach to characterize human T cell-derived exosomes. We found that
      specific proteins of the RAS signaling pathway were enriched in exosomes derived
      from activated T cells, and that these vesicles induced ERK phosphorylation in
      recipient immune cells. Our findings support a mechanistic role of exosomes in
      cellular activation, and further studies should consider exosomes as a biomarker
      for inflammatory diseases.

PMID- 30207597
TI  - Geriatrics Literature 2017 Year in Review.
AB  - We present 11 of the most effective articles from 2017 in geriatric medicine.
      Studies address topics including self-driven advance care planning, unnecessary
      emergency department transfers from assisted living, effect of transcatheter
      aortic valve implantation on cognition, a modified Hospital Elder Life Program to
      reduce delirium after surgery, patient experience and provider understanding of
      nursing home placement, patient perspectives on recommendations to stop cancer
      screening, management of subclinical hypothyroidism, reduction of inappropriate
      medications in nursing homes, effect of lorazepam on end-of-life agitated
      delirium, and benefits of a novel exercise program on walking.

PMID- 30207598
TI  - Leaf adaptations and species boundaries in North American Cercis: implications
      for the evolution of dry floras.
AB  - PREMISE OF THE STUDY: The North American Cercis clade spans dry to mesic climates
      and exhibits complex morphological variation. We tested various proposed species
      classifications of this group and whether aspects of leaf morphology,
      particularly the "drip-tip" in some regional populations, are adaptive and/or
      linked with phylogeny. METHODS: We made measurements on over 1100 herbarium
      specimens from throughout North America and analyzed the data with univariate and
      multivariate approaches. We analyzed phylogenetically DNA sequence data from
      nuclear ITS and three plastid regions from 40 samples, and estimated divergence
      times with a relaxed-clock Bayesian analysis. We used climate and geographic
      position data to predict the variation observed in leaf size and shape by using
      stepwise multiple linear regressions. KEY RESULTS: Morphometric analyses yielded
      a pattern of continuous and often clinal character variation across North
      America, without correlated gaps in character states. Conversely, phylogenetic
      and divergence time analyses yielded distinct clades from California, the
      interior west, and eastern North America separated by between ~12 and 16 million
      years. Multiple regressions yielded highly significant correlations between leaf
      apex shape and precipitation of the warmest quarter. CONCLUSIONS: Despite a
      pattern of continuous morphological character variation, the long period of
      geographic and presumably genetic isolation warrants the delimitation of three
      species. Predictive modeling supports the adaptive value of acuminate apices or
      "drip-tips" in mesic habitats. This suggests that Cercis leaves change more
      rapidly than inferred from parsimony reconstruction, which has implications for
      the evolution of the dry floras of North America and Eurasia.

PMID- 30207599
TI  - Sexuality and Cognitive Status: A U.S. Nationally Representative Study of Home
      Dwelling Older Adults.
AB  - OBJECTIVES: To determine patterns and prevalence of sexual behavior, problems,
      and attitudes in individuals with different cognitive status. DESIGN: We used
      data from the National Social Life, Health, and Aging Project to describe the
      relationship between sexual behavior, function, and cognitive status (normal,
      mild cognitive impairment, dementia), classified using an adapted Montreal
      Cognitive Assessment (MoCA) (0-30 points). SETTING: U.S. home-dwelling older
      adults. PARTICIPANTS: Nationally representative probability sample of 3,196
      adults (1,682 women, 1,514 men) aged 62 to 91 (mean 72). MEASUREMENTS: Cognitive
      status and sexual activity, problems, and attitudes. RESULTS: The weighted
      response rate was 74%. Mean MoCA score was 22.7. Of partnered people with
      dementia, 59% of men and 51% of women were sexually active, including 41% of
      those aged 80 to 91; 46% of all men (95% confidence interval (CI)=37.8-53.2%) and
      18% of all women (95% CI=13.6-21.5%) with dementia were sexually active. The rate
      of sexual function problems was high across gender and cognitive groups (77%).
      Having sex primarily out of obligation was similar across cognitive groups for
      women (12%) and higher in men with dementia (17%) than other men (2-5%; P <.001).
      The majority of people were having sex less often than they would like. Few men
      (17%) or women (1%) with dementia talked with a doctor about sex. CONCLUSION:
      Many home-dwelling men and women with dementia are sexually active. Although the
      rate of sexual function problems was uniformly high, people with lower cognitive
      function infrequently discussed sex with a physician.

PMID- 30207600
TI  - Totally Endoscopic Robotic-Assisted Cardiac Surgery in Children.
AB  - Robotic surgery for intracardiac pathologies in children is relatively uncommon.
      This study presents our initial experience with robotic-assisted cardiac surgery
      in children. We also present the feasibility and safety of robotic surgery in
      children. From May 2013 to June 2018, 30 children underwent totally endoscopic
      robotic atrial septal defect closure (n = 22), right-sided (n = 5) or left-sided
      (n = 1) partial anomalous pulmonary venous connection repair, tricuspid valve
      annuloplasty (n = 4), and mitral valve replacement (n = 2, due to Barlow and
      rheumatic diseases). The mean age of the patients was 16.1 +/- 1.1 years (range,
      13-17) and the mean weight was 56.7 +/- 0.1 kg (range, 42-77). Associated
      anomalies included left persistent superior vena cava (n = 2) and the absence of
      innominate vein (n = 1). All procedures were completed uneventfully. Operation
      time was 4.1 +/- 0.6 h. No patient was converted to thoracotomy or sternotomy.
      Cardiopulmonary bypass and aortic clamping times were 90.6 +/- 28.0 (range, 45
      136) and 48.6 +/- 24.9 (range, 15-94) min, respectively. The mean ventilation
      time was 3.7 +/- 1.2 h and hospital stay time was 3.3 +/- 0.7 days. No right
      phrenic nerve injury, hemorrhage, or blood transfusion were noted. One patient
      had postoperative pneumothorax, and 1 had supraventricular arrhythmia. Follow-up
      was a mean of 1.7 years (range, 1-52 months). Patients were healthy and no
      residual intracardiac defect was observed on echocardiography examinations. There
      was no operative or follow-up mortality. Robotically assisted cardiac surgery is
      a feasible and safe approach in selected pediatric patients. In the future, new
      generation robotic devices may offer an alternative surgical approach in cardiac
      surgery for younger children with lower body weight.

PMID- 30207601
TI  - Alcohol Intake Interacts with CDKAL1, HHEX, and OAS3 Genetic Variants, Associated
      with the Risk of Type 2 Diabetes by Lowering Insulin Secretion in Korean Adults.
AB  - BACKGROUND: Since alcohol intake increases the prevalence of type 2 diabetes
      (T2DM) in Koreans, we tested the hypothesis that the interactions of genetic
      variants involved in beta-cell function and mass with alcohol intake increase the
      T2DM risk. METHODS: The single nucleotide polymorphisms (SNPs) were selected by
      genome-wide association study for insulin secretion after adjusting for age,
      gender, area of residence, body mass index, and alcohol intake (p < 1 * 10-4 ) in
      8,842 middle-aged adults in the Ansan/Ansung cohort. Genetic risk scores (GRSs)
      were calculated by summing the risk alleles of 4 selected SNPs, CDKAL1 rs7754840
      and rs9460546, HHEX rs5015480, and OAS3 rs2072134. The GRSs were categorized into
      3 groups by tertiles, and the association between GRS and insulin secretion was
      measured using logistic regression after adjusting for confounding factors in the
      Ansan/Ansung cohort. The results were confirmed by the Rural cohort. RESULTS:
      HOMA-IR was higher and HOMA-B was much lower in the High-GRS than the Low-GRS in
      both cohorts. T2DM risk was higher by approximately 1.5-fold in the High-GRS than
      in the Low-GRS in both cohorts. In the High-GRS group, HOMA-B decreased by 0.89-
      and 0.62-fold in comparison with the Low-GRS in the Ansan/Ansung cohort and Rural
      cohort. The GRS interacted with alcohol intake to increase the risk of developing
      T2DM in the Ansan/Ansung cohort (p = 0.036) and Rural cohort (p = 0.071). The
      risk of T2DM increased in the High-GRS group with high alcohol intake and it was
      associated with decreased HOMA-B. High alcohol intake decreased HOMA-B regardless
      of GRS, and HOMA-B was lower in the descending order of Medium-GRS, Low-GRS, and
      High-GRS. However, HOMA-IR was not altered by alcohol intake, but was elevated in
      the High-GRS more than in the other groups. CONCLUSIONS: Subjects with a High-GRS
      had an elevated risk of T2DM even with moderate alcohol intakes due to lower HOMA
      B. High alcohol intake appears to be a risk factor for all Asians regardless of
      alcohol intake.

PMID- 30207602
TI  - Risk of stillbirth among Zambian women with a prior cesarean delivery.
AB  - OBJECTIVE: Cesarean delivery (CD) may be associated with stillbirth in future
      pregnancies. We investigated prior CD as a risk factor for stillbirth in Lusaka,
      Zambia. METHODS: We conducted a retrospective cohort analysis of women with only
      one prior pregnancy who delivered between February 1, 2006, and May 31, 2013. We
      analysed data from the Zambia Electronic Perinatal System. Maternal and infant
      characteristics were analyzed for association with stillbirth using Pearson's
      chi2 test or the Wilcoxon rank-sum test. We calculated risk ratios for the
      relationship between stillbirth (antepartum vs intrapartum) and prior CD, with a
      log Poisson model to adjust for confounding. RESULTS: Of 57 320 women in our
      cohort, 1933 (3.4%) reported a prior CD. There were 1012 (1.8%) stillbirths in
      the no prior CD group and 81 (4.2%) in the prior CD group (P<0.001). In
      multivariate models adjusting for stillbirth risk factors, prior CD was
      associated with antepartum (adjusted risk ratio 1.56, 95% confidence interval
      1.08-2.24) and intrapartum (adjusted risk ratio 3.26, 95% confidence interval
      2.40-4.42) stillbirth compared with no prior CD. The difference between groups
      was most apparent at 36-37 weeks' gestation (log-rank P<0.001). CONCLUSION: Prior
      CD was associated with increased risk of stillbirth. Improved monitoring during
      labor and safe methods for induction are urgently needed in low-resource
      settings.

PMID- 30207603
TI  - Chronic Kidney Disease and Third-Generation P2Y12 Inhibitors Use in Patients With
      Acute Coronary Syndrome: Impact on the Prognosis at 1 Year.
AB  - Chronic kidney disease (CKD) is associated with worse clinical outcomes in
      patients with acute coronary syndrome. However, they are underrepresented in
      clinical trials. We aimed to investigate differences in prognosis of acute
      coronary syndrome patients with and without CKD, focusing on the use of novel
      P2Y12 receptor inhibitors. This multicenter registry involved patients with acute
      coronary syndrome from 3 tertiary institutions. After excluding anticoagulated
      patients and patients on antiplatelet monotherapy, 1280 patients remained. During
      1 year of follow-up, we recorded all major adverse cardiovascular events
      (composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal
      ischemic stroke), bleeds (Bleeding Academic Research Consortium classification)
      and deaths. Of 1280 patients, 325 (25.4%) had CKD; 55.5% of non-CKD patients and
      22.7% of CKD patients were prescribed novel P2Y12 inhibitors. During follow-up,
      CKD patients under novel P2Y12 inhibitors showed a not statistically significant
      lower mortality and incidence of thrombotic events than clopidogrel-treated ones.
      In contrast, non-CKD patients taking novel P2Y12 inhibitors had better outcomes
      in terms of major adverse cardiovascular events (4.72 vs 9.41; P = .006), all
      cause mortality (1.32 vs 4.24; P = .006), and severe bleeding events (Bleeding
      Academic Research Consortium 3-5) (0.94 vs 2.82; P = .030), without differences
      for any bleeding (8.11 vs 8.47; P = .849). Bleeding risk was not increased by
      using third-generation P2Y12 inhibitors in either group of patients. In
      conclusion, the use of third-generation P2Y12 inhibitors among non-CKD patients
      was associated with better outcomes. CKD patients receiving third-generation
      P2Y12 inhibitors treatment showed no statistically significant lower mortality
      and thrombotic events. Bleeding risk was not increased with the use of third
      generation P2Y12 inhibitors in either group of patients.

PMID- 30207604
TI  - An Integrated Population Pharmacokinetic Analysis to Characterize Levonorgestrel
      Pharmacokinetics After Different Administration Routes.
AB  - To compare the pharmacokinetics (PK) of the progestin levonorgestrel for various
      routes of administration, an integrated population PK analysis was performed.
      This analysis integrated data from 10 clinical pharmacology studies and resulted
      in a single, comprehensive population PK model (and its applications) describing
      the PK of levonorgestrel and its variability for 6 levonorgestrel-containing
      contraceptives: 3 intrauterine systems (IUSs; levonorgestrel [LNG]-IUS 20
      [Mirena(r) ], LNG-IUS 12 [Kyleena(r) ], and LNG-IUS 8 [Jaydess(r) /Skyla(r) ]); 2
      oral contraceptives (the progestin-only pill [Microlut(r) /Norgeston(r) ] and the
      combined oral contraceptive [Miranova(r) ]); and a subdermal implant (Jadelle(r)
      ). The levonorgestrel-containing contraceptives administered orally or as an
      implant act mainly via their systemic (unbound) levonorgestrel exposure, whereas
      levonorgestrel administered via an IUS is released directly into the uterine
      cavity, resulting in lower systemic levonorgestrel concentrations. The integrated
      population PK analysis revealed that the combined oral contraceptive led to the
      highest levonorgestrel exposure, followed by the progestin-only pill and the
      implant, which led to similar levonorgestrel exposure, and the IUSs, which led to
      the lowest levonorgestrel exposure (in decreasing order: LNG-IUS 20, LNG-IUS 12,
      and LNG-IUS 8). The difference was even more distinct at the end of the indicated
      duration of use of 3 years (LNG-IUS 8) and 5 years (LNG-IUS 20 and LNG-IUS 12).
      Comparing the 3 IUSs and the implant, in vivo release rates were highest for the
      implant, followed by LNG-IUS 20, then LNG-IUS 12, and were lowest for LNG-IUS 8.
      This is in line with the comparison of the total levonorgestrel concentrations.

PMID- 30207605
TI  - A fluorescence toolbox: A review of investigation of electrophoretic separations,
      process, and interfaces.
AB  - This review focuses on fluorescence spectroscopy techniques for the investigation
      of electrophoretic separations. Fluorescence has been used as a sensitive
      detector for capillary, gel, and microchip electrophoresis for decades. However,
      advanced fluorescence methods can be used to study transport, interfacial
      phenomena, intermolecular and affinity interactions, and other processes that
      occur during separation. This so-called spectroscopic toolkit can be implemented
      to understand fundamental behavior in electrophoresis and electrokinetic
      chromatography. Techniques such as fluorescence recovery after photobleaching,
      fluorescence correlation spectroscopy, and fluorescence anisotropy are discussed
      in relation to electrophoretic separations. Newer methods such as super
      resolution microscope are also introduced.

PMID- 30207606
TI  - Reference method for digital surface measurement of target lesions in vitiligo: a
      comparative analysis.
AB  - BACKGROUND: Objective measurement of target lesions in vitiligo is important for
      clinical practice and trials, yet no preferred tool has been defined. Reported
      digital tools have shortcomings related to feasibility aspects and often lack
      information on validity, reliability and responsiveness. Moreover, studies are
      not yet based on ultraviolet (UV) photography. OBJECTIVES: To assess the
      reliability, validity and feasibility of two functions in ImageJ for measurement
      of target lesions, based on three different types of images including UV
      pictures. METHODS: Planimetric measurements were performed on photographs with
      and without UV, and lesion contours on transparent sheets of 52 vitiligo lesions
      from 10 patients with vitiligo. The ImageJ functions 'wand' and 'threshold' were
      used by three and four assessors, respectively. Inter- and intrarater
      reliability, hypothesis testing for construct validity, and feasibility were
      evaluated. RESULTS: The inter- and intrarater reliability for the 'wand' and
      'threshold' functions were excellent [intraclass correlation coefficient (ICC) >
      0.9] for measurement on pictures (with or without UV). The highest agreement (ICC
      > 0.95) and lowest variance were obtained for measurements on transparent sheets.
      All four hypotheses for construct validity were confirmed for all measurements.
      Overall, all measurement methods scored satisfactorily for user-friendliness.
      However, measurements on transparent sheets were preferred and the completion
      time was significantly faster. CONCLUSIONS: This study confirmed the reliability,
      validity and feasibility of two functions in ImageJ to measure target lesions in
      vitiligo. Based on the feasibility and included three-dimensional aspects,
      transparent sheets measured with the ImageJ 'wand' function can be proposed for
      future trials as a reference method to investigate the criterion validity of
      other digital instruments.

PMID- 30207608
TI  - Spin State Energetics of VGe n -/0 (n = 5-7) Clusters and New Assignments of the
      Anion Photoelectron Spectra.
AB  - The geometrical structures, electron leading configurations, and relative
      energies of the low-lying states of VGe n -/0 (n = 5-7) clusters have been
      investigated with density functional theory and CASSCF/CASPT2 method. The pure
      GGA BP86 functional gave almost the same relative energy order for the low-lying
      states as the CASPT2 method. At the BP86 and CASPT2 levels, the ground states of
      VGe n -/0 (n = 5-7) clusters were proposed to be the 1 A1 and 2 A1 of A-VGe5 -/0
      , 3 A" and 2 A", 2 A' (2 E2 ) of A-VGe6 -/0 , and 1 A' and 2 A' of A-VGe7 -/0
      isomers. The adiabatic and vertical detachment energies (ADEs and VDEs) of the
      detachments of one electron from several orbitals of the anionic ground states
      were reported at the CASPT2 level. The calculated ADEs and VDEs corresponded well
      with the experimental values as observed in the 266 nm anion photoelectron
      spectra. (c) 2018 Wiley Periodicals, Inc.

PMID- 30207609
TI  - Pharmacological management of X-linked hypophosphataemia.
AB  - The most common heritable disorder of renal phosphate wasting, X-linked
      hypophosphataemia (XLH), was discovered to be caused by inactivating mutations in
      the phosphate regulating gene with homology to endopeptidases on the X-chromosome
      (PHEX) gene in 1995. Although the exact molecular mechanisms by which PHEX
      mutations cause disturbed phosphate handling in XLH remain unknown, focus for
      novel therapies has more recently been based upon the finding that the bone
      produced phosphaturic hormone fibroblast growth factor-23 is elevated in XLH
      patient plasma. Previous treatment strategies for XLH were based upon phosphate
      repletion plus active vitamin D analogues, which are difficult to manage, fail to
      address the primary pathogenesis of the disease, and can have deleterious side
      effects. A novel therapy for XLH directly targeting fibroblast growth factor-23
      via a humanized monoclonal antibody (burosumab-twza/CRYSVITA, henceforth referred
      to just as burosumab) has emerged as an effective, and recently approved,
      pharmacological treatment for both children and adults. This review will provide
      an overview of the clinical manifestations of XLH, the molecular pathophysiology,
      and summarize its current treatment.

PMID- 30207611
TI  - AbmR (Rv1265) is a novel transcription factor of Mycobacterium tuberculosis that
      regulates host cell association and expression of the non-coding small RNA Mcr11.
AB  - Gene regulatory networks used by Mycobacterium tuberculosis (Mtb) during
      infection include many genes of unknown function, confounding efforts to
      determine their roles in Mtb biology. Rv1265 encodes a conserved hypothetical
      protein that is expressed during infection and in response to elevated levels of
      cyclic AMP. Here, we report that Rv1265 is a novel auto-inhibitory ATP-binding
      transcription factor that upregulates expression of the small non-coding RNA
      Mcr11, and propose that Rv1265 be named ATP-binding mcr11 regulator (AbmR). AbmR
      directly and specifically bound DNA, as determined by electrophoretic mobility
      shift assays, and this DNA-binding activity was enhanced by AbmR's interaction
      with ATP. Genetic knockout of abmR in Mtb increased abmR promoter activity and
      eliminated growth phase-dependent increases in mcr11 expression during hypoxia.
      Mutagenesis identified arginine residues in the carboxy terminus that are
      critical for AbmR's DNA-binding activity and gene regulatory function. Limited
      similarity to other DNA- or ATP-binding domains suggests that AbmR belongs to a
      novel class of DNA- and ATP-binding proteins. AbmR was also found to form large
      organized structures in solution and facilitate the serum-dependent association
      of Mtb with human lung epithelial cells. These results indicate a potentially
      complex role for AbmR in Mtb biology.

PMID- 30207610
TI  - Hemostasis management and therapeutic plasma exchange: Results of a practice
      survey.
AB  - BACKGROUND: Patients undergoing therapeutic plasma exchange (TPE) may present
      with risks for hemorrhage or thrombosis. Use of replacement fluids devoid of
      coagulation factors will decrease factor levels and platelet levels. There are no
      established guidelines for hemostasis management in these situations. MATERIALS
      AND METHODS: A survey to evaluate current hemostasis management practice during
      TPE was conducted using online survey software. One response per institution was
      analyzed based on a hierarchical algorithm, excluding membrane filtration users,
      resulting in a maximum of 107 respondents. Descriptive analysis was performed
      with results reported as the number and frequency (%) of respondents to each
      question. RESULTS: Apheresis Medicine physicians, alone (59.4%) or jointly with
      the requesting provider (29.2%), choose the replacement fluid. Based on a
      theoretical patient case receiving five TPEs approximately every other day, the
      percent of respondents who would use albumin with or without normal saline was
      94.7% with no history of a bleeding or clotting disorder, 1.1% with active
      bleeding, and 8.8% with hypofibrinogenemia (<100 mg/dL) due to recent TPE. More
      respondents would use albumin with or without normal saline for replacement fluid
      when a minor invasive procedure (49.5%) vs a major surgery (8.9%) was performed 1
      day before TPE. Replacement fluid selection varied among respondents for several
      other clinical conditions. The most frequent use for cryoprecipitate by
      respondents (14.3%) was hypofibrinogenemia. CONCLUSIONS: These survey results
      demonstrate wide interinstitutional variation in replacement fluid selection to
      manage hemostasis in patients undergoing TPE. Further studies are needed to guide
      optimal hemostasis management with TPE.

PMID- 30207612
TI  - The common meanings and shared practices of sedation assessment in the context of
      managing patients with an opioid: A phenomenological study.
AB  - AIMS AND OBJECTIVES: To examine the common meanings of opioid-induced sedation
      and shared practices in the context of post-operative pain management in expert
      Post-Anesthesia Care Unit nurses during patient's pain management with opioids.
      BACKGROUND: Within the clinical setting, linear pain and sedation scales are not
      enough to support clinical judgement with acute pain management. Because sedation
      measurement rests along a fluctuating continuum, it is possible for a patient to
      be sedated and then shift to increasing alertness, and then to drift back to a
      sedated state. This potential for acute clinical transition can be challenging to
      nurses of all levels, even for expert nurses. DESIGN: Interpretive phenomenology.
      METHODS: Twenty expert Post-Anesthetic Care Unit nurses, with more than 7 years
      of nursing experience, participated in qualitative interviews regarding their
      lived experiences. Interviews were analysed using a modified seven-stage process
      for interpretation by Diekelmann, Allen and Tanner. The manuscript was developed
      utilising the COREQ guidelines for reporting qualitative studies. RESULTS: Four
      themes identified through the participant's stories were recognising every
      patient is different, engaging in iterative knowing, walking a fine line, and
      looking beyond and anticipating. This study identified a constitutive pattern of
      interpreting sedation by integrating practical understanding and anticipating
      beyond. CONCLUSIONS: This study indicates a deeper complexity in the way opioid
      induced sedation is assessed and balanced with pain management by nurses in the
      Post-Anesthetic Care Unit. RELEVANCE TO PRACTICE: Nurses in the study adapted
      their practices around pain management with opioids, in response to their
      patient's level of sedation; incorporating practices such as giving small,
      incremental doses and changing the drug. Nurses valued the importance of having
      "eyeballs on everybody" and being ready to meet the needs of their patient. They
      appreciate the time to watch and wait for their patient to respond, to better
      judge the result of their interventions.

PMID- 30207613
TI  - Searching for meaning: A grounded theory of family resilience in adult ICU.
AB  - AIM: To explore families' experiences of their interactions in an Australian
      adult intensive care unit (ICU) to develop a grounded theory that can be used by
      critical care nurses to improve patient- and family-centred care (PFCC).
      BACKGROUND: Families in ICU play an important role in the patient's recovery and
      outcomes. However, families are at risk of significant psychological morbidity
      due to their experiences in ICU. Although many ICU patients can make their own
      decisions, a large proportion are unconscious or chemically sedated and unable to
      contribute to decisions about their care, leaving the decision-making role to the
      family. Therefore, the families' psychosocial and emotional well-being must be
      supported by implementing evidence-based interventions that align with a PFCC
      approach. This study describes the findings of a grounded theory of family
      resilience in ICU, of which the core category is Regaining control. The focus of
      this paper is on the major category: Searching for meaning. METHODS: We adopted a
      constructivist grounded theory method. Twenty-five adult family members (n = 25)
      of 21 patients admitted unexpectedly to an ICU in metropolitan Australia were
      recruited. In-depth interviews were used to collect the data, and the analytical
      processes of constructivist grounded theory underpinned the development of a core
      category and related subcategories. RESULTS: When adult family members experience
      the unexpected admission of a relative to ICU, they move towards a state of being
      beyond emotional adversity and regaining control when facilitated to search for
      meaning in their situation. When families were able to make sense of their
      situation and find a purpose by contributing to their relative's recovery, it
      encouraged them to cope and be resilient. CONCLUSIONS: Our findings can be used
      to promote PFCC in ICU, which considers a collaborative approach to meet the
      patient's needs while providing emotional and psychosocial support to their
      families.

PMID- 30207614
TI  - Risk of drowning in people with Parkinson's disease.

PMID- 30207616
TI  - The relations among animal abuse, psychological disorders, and crime:
      Implications for forensic assessment.
AB  - The confluence of developments in the assessment of animal abuse, the evolution
      of psychiatric nosology for the diagnosis of conduct disorder, legislative
      changes involving crimes against non-human animals, and the recent inclusion of
      crimes against animals in the FBI's National Incident-Based Reporting System,
      highlights the critical need for examining the forensic dimensions of animal
      abuse cases. We provide an overview of the research literature on these topics in
      the hope that forensic evaluators will have an evidence-based framework for
      assessing cases they encounter that include perpetration of violence against
      animals.

PMID- 30207618
TI  - Tuning of Structural Colors Like a Chameleon Enabled by Shape-Memory Polymers.
AB  - Nature often uses structuring of materials for coloration rather than
      incorporating dye molecules, since single-construction materials are capable of
      producing any vivid visible color in plants and insects. By precisely engineering
      features that diffract or scatter light, more recently, humans have created
      similarly intense non-fading colors. Stretchable polymer opals have emerged as a
      single material which can dynamically shift across the whole visible spectrum
      using structural colors, by temporary stretching or compression. For energy
      efficiency and practical considerations, however, it is necessary to fix semi
      permanently desired colors without continuous stretching or application of other
      stimuli or energy. Here, a polymer opal incorporating a shape-memory polymer
      embedded in its matrix can keep a particular color fixed without the application
      of external forces, yet can be reprogrammed to a different fixed color on demand.
      The influence of the material composition on its optical appearance, shape
      fixity, and shape recovery abilities in controlled stretch experiments is
      quantified. High-speed printing-compatible localized compression pattern
      imprinting is shown to generate stable but easily erasable color patterns. This
      opens up the potential for durable and energy-efficient yet reusable and
      reconfigurable displays, wearables, or packaging and security labeling based on
      such polymeric film materials.

PMID- 30207617
TI  - Association of early pregnancy body mass index and children's birth weight with
      risk of being overweight in childhood.
AB  - OBJECTIVES: To examine the potential effects of mothers' early pregnancy body
      mass index (BMI) and children's birth weight on childhood overweight/obesity at 1
      6 years of age. METHODS: We performed a cohort study in Tianjin, China, using the
      health care records from the Tianjin maternal and child health care system with
      36 719 mother-child pairs from early pregnancy to children at 6 years of age.
      Logistic regression analyses were used to assess the single and joint
      associations of maternal early pregnancy BMI and children's birth weight with the
      risks of children being overweight at 1-6 years of age in multivariable-adjusted
      models. RESULTS: Both maternal early pregnancy BMI and children's birth weight
      were positively associated with the risk of children being overweight at 1-6
      years of age. Compared with children who were born to normal weight mothers and
      had low or normal birth weight (NBW; birth BMI < 85%), higher risks of being
      overweight at 1-6 years were found among children with low or NBW who were born
      to overweight mothers, and children with high NBW (BMI >= 85%) or macrosomia who
      were born to normal weight or overweight mothers. Lower risks of being overweight
      were found among those with low birth weight who were born to normal weight
      mothers. CONCLUSIONS: Maternal early pregnancy BMI may play a more important role
      than children's birth weight in the risk of being overweight from 4 to 6 years of
      age. Children with high or NBW need to be given more attention to prevent
      excessive weight gain.

PMID- 30207619
TI  - Randomized, double-blind, multicenter trial of hydrogen water for Parkinson's
      disease.

PMID- 30207620
TI  - High-Value MRI.

PMID- 30207621
TI  - A Universal Strategy to Design Superior Water-Splitting Electrocatalysts Based on
      Fast In Situ Reconstruction of Amorphous Nanofilm Precursors.
AB  - The development of efficient bifunctional electrodes with extraordinary mass
      activity and robust stability is an eternal yet challenging goal for the water
      splitting process. Surface reconstruction during electrocatalysis can form fresh
      composition electrocatalysts with unusual amorphous phases in situ, which are
      more active but difficult to prepare by conventional methods. Here, a facile
      strategy based on fast reconstruction of amorphous nanofilm precursors is
      proposed for exploring precious-metal-free catalysts with good electronic
      conductivity, ultrahigh activity, and robust stability. As a proof of concept, an
      amorphous SrCo0.85 Fe0.1 P0.05 O3- delta (SCFP) nanofilm precursor with weak
      chemical bonds deposited onto a conductive nickel foam (NF) substrate (SCFP-NF)
      is synthesized by utilizing a high-energy argon plasma to break the strong
      chemical bonds in a crystalline SCFP target. The quickly reconstructed SCFP-NF
      bifunctional catalysts show ultrahigh mass activity of up to 1000 mA mg-1 at an
      overpotential of 550 mV and extremely long operational stability of up to 650 h
      at 10 mA cm-2 , significantly overperforming state-of-the-art precious-metal
      catalysts. Such a strategy is further demonstrated to be a universal method,
      which can be applied to accelerate the reconstruction of other material systems
      to obtain various efficient electrocatalysts.

PMID- 30207622
TI  - Hot off the Press: SGEM #226. I Want a New Drug-One That Doesn't Cause an Adverse
      Drug Event.
AB  - Adverse drug events (ADEs) are a significant cause of emergency department (ED)
      visits in North America and are frequently misdiagnosed. Despite evidence
      supporting improved health care outcomes for ED patients who have a pharmacist
      led medication review, EDs do not have sufficient clinical pharmacists to perform
      medication reviews on all patients. The study reviewed in this article aimed to
      validate clinical decision rules for use by clinical pharmacists and physicians
      to prioritize ED patients with ADEs.

PMID- 30207623
TI  - Microscopic malaria parasitemia diagnosis and grading on benchmark datasets.
AB  - Malaria parasitemia diagnosis and grading is hard and still far from perfection.
      Inaccurate diagnosis and grading has caused tremendous deaths rate particularly
      in young children worldwide. The current research deeply reviews automated
      malaria parasitemia diagnosis and grading in thin blood smear digital images
      through image analysis and computer vision based techniques. Actually, state-of
      the-art reveals that current proposed practices present partially or morphology
      dependent solutions to the problem of computer vision based microscopy diagnosis
      of malaria parasitemia. Accordingly, a deep appraisal of the current practices is
      investigated, compared and analyzed on benchmark datasets. The open gaps are
      highlighted and the future directions are laid down for a complete automated
      microscopy diagnosis for malaria parasitemia based on those factors that have not
      been affected by other diseases. Moreover, a general computer vision framework to
      perform malaria parasitemia estimation/grading is constructed in universal
      directions. Finally, remaining problems are highlighted and possible directions
      are suggested. RESEARCH HIGHLIGHTS: The current research presents a microscopic
      malaria parasitemia diagnosis and grading of malaria in thin blood smear digital
      images through image analysis and computer vision based techniques. The open gaps
      are highlighted and future directions for a complete automated microscopy
      diagnosis of malaria parasitemia mentioned.

PMID- 30207624
TI  - Nanometer-scale Multiplexed Super-Resolution Imaging with an Economic 3D-DNA
      PAINT Microscope.
AB  - Optical super-resolution microscopy is rapidly changing the way imaging studies
      in the biological and biomedical sciences are conducted. Due to the unique
      capability of achieving molecular contrast using fluorescent labels and sub
      diffraction resolution down to a few tens of nanometers, super-resolution is
      developing as an attractive imaging modality. While the increased spatial
      resolution has already enabled structural studies at unprecedented molecular
      detail, the wide-spread use of super-resolution approaches as a standard
      characterization technique in biological laboratories has thus far been prevented
      by mainly two issues: (1) Intricate sample preparation and image acquisition and
      (2) costly and complex instrumentation. We here introduce a combination of the
      recently developed super-resolution technique DNA-PAINT (DNA points accumulation
      for imaging in nanoscale topography) with an easy-to-replicate, custom-built 3D
      single-molecule microscope (termed liteTIRF) that is an order of magnitude more
      economic in cost compared to most commercial systems. We assay the performance of
      our system using synthetic two- and three-dimensional DNA origami structures and
      show the applicability to single- and multiplexed cellular imaging.

PMID- 30207625
TI  - How [Fe]-Hydrogenase from Methanothermobacter is Protected Against Light and
      Oxidative Stress.
AB  - [Fe]-hydrogenase (Hmd) catalyzes the reversible hydrogenation of
      methenyltetrahydromethanopterin (methenyl-H4 MPT+ ) with H2 . Hmd contains the
      iron-guanylylpyridinol (FeGP) cofactor, which is sensitive to light and oxidative
      stress. A natural protection mechanism is reported for Hmd based on structural
      and biophysical data. Hmd from Methanothermobacter marburgensis (mHmd) was found
      in a hexameric state, where an expanded oligomerization loop is detached from the
      dimer core and intrudes into the active site of a neighboring dimer. An aspartic
      acid residue from the loop ligates to FeII of the FeGP cofactor and thus blocks
      the postulated H2 -binding site. In solution, this enzyme is in a hexamer-to
      dimer equilibrium. Lower enzyme concentrations, and the presence of methenyl-H4
      MPT+ , shift the equilibrium toward the active dimer side. At higher enzyme
      concentrations-as present in the cell-the enzyme is predominantly in the inactive
      hexameric state and is thereby protected against light and oxidative stress.

PMID- 30207626
TI  - Metasummary is a useful way of synthesising quantitative and qualitative data.

PMID- 30207627
TI  - Macroautophagy Regulates Nuclear NOTCH1 Activity Through Multiple p62 Binding
      Sites.
AB  - NOTCH1 is the prototype of the NOTCH family of single-pass transmembrane
      receptors and regulates many basic processes during embryonic development and
      human pathogenesis. In core to NOTCH1 activation are proteolytic cleavages that
      release its intracellular domain (NICD1), which in turn translocates to the
      nucleus to regulate gene transcription. Macroautophagy (hereafter autophagy) has
      been shown to promote the degradation of NOTCH1, but the underlying mechanisms
      remain elusive. Here, we show that autophagy promotes the degradation of NOTCH1
      by p62-dependent binding between NICD1 and LC3, a component of the autophagosomes
      that execute autophagy. Strikingly, deleting any of the structural NICD1 domains
      fails to block the degradation of NICD1 by autophagy, and p62 binds to almost all
      these domains independently, indicating that p62 binds to multiple sites on NICD1
      to promote its degradation. Intriguingly, inhibition of autophagy induces the
      accumulation of NICD1 in not only the cytoplasm but also the nucleus and
      increases the transcriptional activity of NICD1, and such regulation of nuclear
      NICD1 by autophagy is unique to NICD1 and not observed for all other NICDs (NICD2
      4). Collectively, our results suggest that autophagy tightly controls nuclear
      NOTCH1 activity through multiple p62 binding sites, and that modulating autophagy
      activity may be useful for treating NOTCH1 related human diseases. (c) 2018 IUBMB
      Life, 70(10):985-994, 2018.

PMID- 30207628
TI  - Risk factors for traumatic dental injuries in the Brazilian population: A
      critical review.
AB  - BACKGROUND/AIMS: Strategies for the prevention of traumatic dental injuries (TDI)
      should consider the risk factors involved for each population studied. The aim of
      this study was to perform a critical review regarding the risk factors for TDI in
      the Brazilian population. MATERIALS AND METHODS: A systematic literature search
      was performed in the MEDLINE, Scopus, Web of Science, Lilacs, and BBO databases
      using MeSH terms, synonyms, and keywords, with no language or date restrictions.
      In the first step, all relevant studies identified, regardless of the type of
      statistical analysis performed, were grouped according to their geographic
      location. In a second step, the studies using Andreasen's criteria to classify
      the injuries and multivariate analysis to identify the risk factors for TDI in
      Brazilian subjects were included for data extraction. RESULTS: The search
      strategy initially identified 3373 articles. However, only 108 articles assessed
      TDI with predisposing factors and were included in the first step. From those, 28
      were deemed eligible for inclusion in the second step. No consensus related to
      the relationship between gender and TDI in the primary dentition was achieved.
      Nonetheless, males were found to be more prone to trauma in the permanent
      dentition. Overjet, inadequate lip sealing and anterior open bite increased the
      risk for TDI, both in primary and permanent dentitions. Social environment was
      related to trauma only in primary dentition. For permanent dentition, dental
      caries, obesity, binge drinking, and drug use were identified as considerable
      risk factors for TDI. CONCLUSION: The risk factors for TDI in the Brazilian
      population are similar to those found worldwide. However, some differences can be
      observed, such as gender and socioeconomic indicators as predisposing factors.

PMID- 30207629
TI  - Periodontal status of anterior teeth following clinical crown lengthening by
      minimally traumatic controlled surgical extrusion.
AB  - BACKGROUND/AIMS: The number of fractured anterior teeth following trauma has been
      increasing while not every patient is able to afford a dental implant instead of
      maintaining the injured tooth. Thus, a tooth conservation solution is required to
      place an aesthetic and functional restoration without biologic width violation.
      The aim of this study was to evaluate the effectiveness of minimally traumatic
      controlled surgical extrusion in fractured anterior teeth crown lengthening by
      assessing the periodontal status through clinical examination and radiographs.
      METHODS: This longitudinal observational study investigated a group of 18
      patients (six males and 12 females) at the Department of Periodontology, National
      Hospital of Odonto-stomatology, Ho Chi Minh City, Vietnam. Following pre-surgery
      procedures and examination, minimally traumatic controlled surgical extrusion was
      carried out using a periotome. Patients were examined at four follow-up
      appointments after 1 week, 1, 3 and 6 months to record the following experimental
      variables: periodontal parameters including the gingival index (GI), pocket depth
      (PD), bleeding on probing (BOP), mobility, marginal gingiva position, alveolar
      ridge resorption, periapical osteogenesis, tooth resorption and ankylosis.
      RESULTS: All periodontal parameters were significantly decreased at 3 and 6
      months post-procedure (P < 0.001). Tooth mobility decreased gradually following
      surgery, and at 6 months, all teeth became normal at level 0. Periapical
      osteogenesis changes were significantly increased at 1, 3 and 6 months in
      comparison with pre-surgery (P < 0.001). Marginal gingiva position and alveolar
      ridge resorption were not significantly different between pre-surgery and 1, 3
      and 6 months post-surgery. No cases of root resorption or ankylosis were observed
      at 6 months post-surgery. CONCLUSION: A minimally traumatic controlled surgical
      extrusion technique for clinical crown lengthening yielded highly successful
      results in both aesthetic and functional aspects, and no cases had unfavourable
      outcomes during the 6-month follow-up period.

PMID- 30207630
TI  - Electrostatic Origins of Linear Scaling Relationships at Bifunctional Metal/Oxide
      Interfaces: A Case Study of Au Nanoparticles on Doped MgO Substrates.
AB  - Linear scaling relationships (SRs), which relate binding energies of adsorbates
      across a space of catalyst surfaces, have been extensively explored for metal and
      oxide surfaces, but little is known about their properties at interfaces between
      metal nanoparticles and oxide supports, which are ubiquitous in heterogeneous
      catalysis. Using periodic DFT calculations, scaling principles are extended to
      bifunctional Au/oxide interfaces. Adopting a Au nanorod on doped MgO (100) as a
      model, SRs for species participating in water gas shift, methanol synthesis, and
      oxidation reactions are reported. SR slopes are not constrained by the bond order
      conservation rule postulated for metals, oxides, and zeolites, potentially
      permitting greater flexibility in catalyst design strategies. The deviation from
      bond counting, along with the physical origin of scaling behavior at interfaces,
      are explored using a conceptual framework involving electrostatic interactions at
      the Au/oxide interface.

PMID- 30207631
TI  - Orexin A Suppresses Oxidized LDL Induced Endothelial Cell Inflammation via MAPK
      p38 and NF-kappaB Signaling Pathway.
AB  - Orexin A is a multifaceted peptide produced in hypothalamus. We examined the
      effect of orexin A on vascular endothelial cells. Our study showed that orexin A
      had a profound inhibitory effect against endothelial inflammation by oxidized low
      density lipoprotein (ox-LDL) in endothelial cells. Orexin A partially suppressed
      ox-LDL-induced monocytes THP-1 cells attachment to endothelial cells by limiting
      expression of vascular molecules including VCAM-1, ICAM-1, and E-selectin.
      Mechanistically, orexin A ameliorated endothelial dysfunction by reducing MAP
      kinase p38 and NF-kappaB activation via its receptor-OX1R. Orexin A suppressed
      phosphorylation of MAP kinase p38 and the NF-kappaB cascade kinases IKKalpha and
      IkappaBalpha, and prevented the shuttle of p65 protein into nuclear.
      Additionally, we reported that OX1R was expressed in HUVECs. Silence of OX1R
      completely abolished the inhibitory function of orexin in attachment of THP-1
      cells. Collectively, our data suggest that orexin A ameliorated endothelial
      dysfunction under inflammatory stimuli. (c) 2018 IUBMB Life, 70(10):961-968,
      2018.

PMID- 30207632
TI  - Biological Evaluation of a New Lignan from the Roots of Rice (Oryza sativa).
AB  - LC/MS-based phytochemical analysis of an EtOH extract of the roots of rice (Oryza
      sativa; Gramineae), which takes a crucial role in the stable crop population in
      Asia, resulted in the isolation of a new lignan, oryzativol C (1), as a minor
      component. The chemical structure of compound 1 was unambiguously confirmed using
      spectroscopic evidence (including 1D- and 2D-NMR data), HR-ESI-MS, and CD data
      analysis. Considering the traditional medicinal efficacy of O. sativa and its
      importance as a food crop, compound 1 was evaluated for effects on breast cancer
      cell lines (MDA-MB-231) and on glucose-stimulated insulin secretion in an INS-1
      pancreatic beta-cell line. Compound 1 showed mild cytotoxicity toward the MDA-MB
      231. Furthermore, compound 1 stimulated insulin secretion in INS-1 pancreatic
      beta-cells without inducing cytotoxicity. These results indicate that compound 1
      is an active ingredient of O. sativa that offers health benefits including
      inhibition of breast cancer cell proliferation and hyperglycemia control.

PMID- 30207634
TI  - Variation in Essential Oil Composition, Bioactive Compounds, Anatomical and
      Antioxidant Activity of Achillea aucheri, an Endemic Species of Iran, at
      Different Phenological Stages.
AB  - In the present research, the essential oil composition, bioactive compounds,
      anatomical and antioxidant activity of Achillea aucheri were investigated at four
      phenological stages. The yield of essential oil ranged from 0.1 % (five leaves
      appearance stage) to 0.7 % (full flowering stage). So, the oils from the plants
      harvested at the full flowering stage provided higher essential oil contents than
      those at other stages. The analysis of the essential oils by GC/MS revealed the
      presence of a large number of components represented mainly by oxygenated
      monoterpenes (24.36-77.81 %). The compounds revealed high variation at different
      phenological stages. The major constituents of A. aucheri were carvacrol (1.07
      19.17 %), camphor (5.44-9.99 %), delta-cadinene (0.20-13.88 %), thymol (2.15-7.80
      %), germacrene D (4.50-7.24 %), 1,8-cineole (1.62-5.54 %) and alpha-terpineol
      (1.71-3.42 %). The total phenolic (51.63 mg tannic acid/g DW) and flavonoid
      (10.88 mg quercetin/g W) contents were more accumulated at the 50 % flowering
      stage than others. The results revealed that the accumulation of essential oil in
      A. aucheri increased as the plant grew from the five leaves appearance stage to
      the 100 % flowering stage with increasing the size and number of secretory
      structures. Finally, the extracts collected at the 50 % flowering stage showed
      the highest antioxidant activity as measured based on FTC and DPPH method with
      the IC50 values ranging from 719.65 MUg/mL to 1039.17 MUg/mL for the samples.

PMID- 30207633
TI  - Utility of a screening tool for haemostatic defects in a multicentre cohort of
      adolescents with heavy menstrual bleeding.
AB  - INTRODUCTION: Heavy menstrual bleeding (HMB) may be expected for many adolescents
      after menarche. Accurate assessment of HMB, a key component in the diagnosis of a
      haemostatic defect (HD), is a well-recognized challenge. AIM: Our objective was
      to determine the diagnostic accuracy of an HMB-specific screening tool for HDs in
      adolescents with HMB, presenting to a secondary care setting. METHODS:
      Adolescents with HMB were evaluated for a HD at 4 US centres. A screening tool,
      the Philipp Tool, developed and validated in adult women with HMB, was
      administered. We modified the tool by assigning a score based on the number of
      affirmative responses. Sensitivity, specificity and likelihood ratios (LRs) of a
      positive tool, modified tool, with a pictorial blood assessment chart (PBAC)
      score >185, and with serum ferritin <=20 ng/mL were calculated for HDs. RESULTS:
      Among 248 adolescents with HMB, 29% were diagnosed with HDs. Sensitivity,
      specificity and LR of a positive screening tool for HDs were 95% (range 88-99),
      14% (9-21) and 1.1 (1-1.2), respectively. A score of >=2, addition of a PBAC
      score >185 and ferritin <=20 ng/mL changed the sensitivity, specificity and LR of
      the tool to 72% (61-81), 94% (83-99), 76% (65-85); 60% (53-68), 24% (16-34) and
      39% (31-47) and 1.8 (1.4-2.2), 1.2 (1.1-1.4) and 1.2 (1-1.4), respectively.
      CONCLUSION: Although sensitive, the discriminative ability of the tool to
      identify adolescents with HDs from those without, who presented with HMB, was
      low. Further research is needed to optimize or develop an adolescent-specific HMB
      tool for secondary care settings.

PMID- 30207635
TI  - Solitary tumor of the forearm.

PMID- 30207636
TI  - Otolaryngological features in a cohort of patients affected with 22q11.2 deletion
      syndrome: A monocentric survey.
AB  - Otorhinolaryngologic manifestations are common in 22q11.2 deletion syndrome
      (22q11.2DS), but poorly described. This study aimed to better define the ear-nose
      throat (ENT) phenotype of 22q11.2DS patients, in the attempt to best detect
      subjects requiring subspecialist intervention. We enrolled 25 patients affected
      with 22q11.2DS. Anatomic and functional ENT findings were investigated using
      clinical, laboratory, and instrumental data. Immunophenotype and frequency of
      infections were evaluated. Univariate and multivariate analyses were performed.
      ENT anomalies were found in 88% of patients, and in 20% congenital palate defects
      required surgery. Adenoid or palatine tonsil hypertrophy was noted in 80% and
      48%. Forty-eight percent of subjects had rhinolalia/phonia, severe in half of
      these. We also found nasal regurgitation or laryngeal penetration/aspiration in
      20% and 16%, respectively. Instrumental exams revealed a mild conductive hearing
      loss in 32% (bilateral in most cases), tympanometric anomalies in 28%, and
      swallowing abnormalities in 16%. Statistical univariate analysis showed a direct
      association between rhinolalia/phonia and episodes of laryngeal aspiration (p =
      .016) and between tympanometric anomalies and increased adenoid volume (p =
      .044). No association between episodes of food aspiration and palatal anomalies
      was found. Moreover, no statistically significant association was observed
      between the number of airway infections and the ENT findings. This study
      contributes to better define the ENT phenotype in patients with 22q11.2DS,
      helpful to prevent potential complications. Furthermore, the identification of a
      subcategory of patients may allow the early adoption of specific speech therapy
      programs to improve the clinical outcome of 22q11.2DS patients.

PMID- 30207637
TI  - Rapid palatal expansion (RPE): Meta-analysis of long-term effects.
AB  - OBJECTS: Rapid palatal expansion (RPE) is a widespread orthopaedic procedure used
      in several clinical situations. The aim of the study was to provide a systematic
      review and meta-analysis of transverse intercanine and intermolar width changes
      after RPE and long-term effects. SETTING AND SAMPLE POPULATION: A systematic
      literature search was conducted until January 2018 on original studies with RPE
      treatment. MATERIAL AND METHODS: Intercanine and intermolar distance were
      measured at the start of RPE (T1, median age 9.2 years) and at the end of
      treatment (T2). The long-term evaluation was conducted on a subset of articles
      with 5-year follow-up (T3). RESULTS: Eighteen studies T1-T2 and 5 studies T3 were
      selected. Regarding the intercanine distance, the RPE resulted in a gain of space
      T1-T2 of 3.73 mm with a significant heterogeneity (P < 0.0001; I2  = 94.21%) and
      a relapse T2-T3 of -0.81 mm with a significant heterogeneity (P < 0.0001; I2  =
      95.8%); the overall gain of space was 2.91 mm. Regarding the intermolar distance,
      the RPE resulted in a gain of space T1-T2 of 4.85 mm with a significant
      heterogeneity (P < 0.0001; I2  = 92.41%) and a relapse T2-T3 of -0.47 mm with a
      significant heterogeneity (P < 0.0001; I2  = 87.5%); the overall gain of space
      was 4.38 mm. Meta-regression analysis showed that at younger age, the amount of
      anterior expansion is similar to posterior. With increasing age, the anterior
      opening diminishes significantly more than the posterior, being half of the
      posterior at 15 years. CONCLUSION: Because long-term results were obtained with
      simultaneously fixed appliances and long upper retention, RPE should be carefully
      considered before using.

PMID- 30207638
TI  - The development of children's preferences for equality and equity across 13
      individualistic and collectivist cultures.
AB  - A concern for fairness is a fundamental and universal element of morality. To
      examine the extent to which cultural norms are integrated into fairness
      cognitions and influence social preferences regarding equality and equity, a
      large sample of children (N 2,163) aged 4-11 were tested in 13 diverse countries.
      Children participated in three versions of a third-party, contextualized
      distributive justice game between two hypothetical recipients differing in terms
      of wealth, merit, and empathy. Social decision-making in these games revealed
      universal age-related shifts from equality-based to equity-based distribution
      motivations across cultures. However, differences in levels of individualism and
      collectivism between the 13 countries predicted the age and extent to which
      children favor equity in each condition. Children from the most individualistic
      cultures endorsed equitable distributions to a greater degree than children from
      more collectivist cultures when recipients differed in regards to wealth and
      merit. However, in an empathy context where recipients differed in injury,
      children from the most collectivist cultures exhibited greater preferences to
      distribute resource equitably compared to children from more individualistic
      cultures. Children from the more individualistic cultures also favored equitable
      distributions at an earlier age than children from more collectivist cultures
      overall. These results demonstrate aspects of both cross-cultural similarity and
      divergence in the development of fairness preferences.

PMID- 30207639
TI  - Single-Site Ruthenium Pincer Complex Knitted into Porous Organic Polymers for
      Dehydrogenation of Formic Acid.
AB  - Owing to its capacity for reversible hydrogen storage, formic acid (FA) holds
      great promise as an alternative energy carrier to conventional fossil fuel
      systems. Whereas the decomposition of FA to hydrogen (H2 ) and carbon dioxide
      (CO2 ) through homogeneous catalysis is well established, the selective and
      efficient dehydrogenation of FA by a robust heterogeneous catalyst remains a
      challenge. A new heterogeneous ruthenium pincer framework with single-atomic
      sites was prepared in one step by the direct knitting of a phosphorus-nitrogen
      PN3 P-pincer ruthenium complex in a porous organic polymer. The heterogeneous
      ruthenium complex efficiently dehydrogenates formic acid in both organic and
      aqueous media with remarkably enhanced stability. Notably, no detectable CO was
      generated and a turnover number (TON) of 145 300 was attained in a continuous
      experiment with no significant decline in catalytic activity (in sharp contrast,
      a total TON of only 5600 was obtained with the homogeneous analog under the same
      conditions). The single-atomic sites in the porous framework combined the
      desirable attributes of high reactivity and selectivity of a homogeneous catalyst
      with the significantly enhanced catalyst stability and reusability benefits of
      heterogeneous catalysis.

PMID- 30207640
TI  - Oxygen Vacancy Engineering in Tin(IV) Oxide Based Anode Materials toward Advanced
      Sodium-Ion Batteries.
AB  - A high theoretical capacity of approximately 1400 mA h g-1 makes SnO2 a promising
      anode material for sodium-ion batteries (SIBs). However, large volume expansion,
      poor intrinsic conductivity, and sluggish reaction kinetics have greatly hindered
      its practical application. The controlled creation of oxygen vacancy (OV) defects
      allows the intrinsic properties of SnO2 to be effectively modulated, but related
      work concerning SIBs is still lacking. In this Minireview, the mechanism of
      failure of SnO2 electrodes is discussed and an overview of recent progress in the
      general synthesis of OV-containing SnO2 materials and the feasible detection of
      OVs in SnO2 is presented. The use of OV-containing SnO2 -based anode materials in
      SIBs is also reviewed. Finally, challenges and future opportunities to engineer
      OVs for semiconductor oxides are examined.

PMID- 30207641
TI  - Longitudinal relationships between speech perception, phonological skills and
      reading in children at high-risk of dyslexia.
AB  - Speech perception deficits are commonly reported in dyslexia but longitudinal
      evidence that poor speech perception compromises learning to read is scant. We
      assessed the hypothesis that phonological skills, specifically phoneme awareness
      and RAN, mediate the relationship between speech perception and reading. We
      assessed longitudinal predictive relationships between categorical speech
      perception, phoneme awareness, RAN, language, attention and reading at ages 51/2
      and 61/2 years in 237 children many of whom were at high risk of reading
      difficulties. Speech perception at 51/2 years correlated with language,
      attention, phoneme awareness and RAN concurrently and was a predictor of reading
      at 61/2 years. There was no significant indirect effect of speech perception on
      reading via phoneme awareness, suggesting that its effects are separable from
      those of phoneme awareness. Children classified with dyslexia at 8 years had
      poorer speech perception than age-controls at 51/2 years and children with
      language disorders (with or without dyslexia) had more severe difficulties with
      both speech perception and attention control. Categorical speech perception tasks
      tap factors extraneous to perception, including decision-making skills. Further
      longitudinal studies are needed to unravel the complex relationships between
      categorical speech perception tasks and measures of reading and language and
      attention.

PMID- 30207642
TI  - Fluctuations in Dissolved Oxygen Concentration During a CHO Cell Culture Process
      Affects Monoclonal Antibody Productivity and the Sulfhydryl-Drug Conjugation
      Process.
AB  - During a CHO cell culture production process, important parameters are generally
      well controlled by a feedback mechanism (PID loop) in order to ensure consistency
      in both productivity and product quality. These parameters typically include pH,
      dissolved oxygen (DO), and temperature. While most of these parameters are very
      well controlled within their specific deadband, stable DO control can be
      challenging. Oscillations in DO concentration are not uncommon and these
      fluctuations can be exacerbated with an efficient mass transfer aeration
      strategy. In this study, where an IgG2 producing cell line was used, we observed
      increased lactate accumulation accompanied by decreased titer production in lots
      with fluctuations in DO concentration (DOF ) when compared with lots with stable
      DO control (DOS ). We demonstrate that DOF had a greater impact on performance
      with respect to titer production and lactate accumulation than DO setpoint.
      Furthermore, we report that estimated specific oxygen uptake rates (qOURs) were
      lower in DOF lots when compared with DOS lots. We also report that purified mAb
      sourced from DOF lots yielded lower drug-to-antibody ratio (DAR) after the
      sulfhydryl-targeted maleimide conjugation process when equivalent reducing agent
      was used. All mAb lots were within the analytical specifications for release,
      though a slight increase in measureable trisulfides were observed in DOF mAb
      lots. DO control aimed to minimize fluctuations around DO setpoint was essential
      for us to produce consistent DAR without adjusting the conjugation process. (c)
      2018 American Institute of Chemical Engineers Biotechnol. Prog., 2018.

PMID- 30207643
TI  - The prevalence and risk factors of venous thromboembolism in hospitalized
      patients with acute exacerbation of chronic obstructive pulmonary disease.
AB  - INTRODUCTION: Venous thromboembolism (VTE) in patients with acute exacerbation of
      chronic obstructive pulmonary disease (AECOPD) is not rare, which would affect
      the patient's prognosis. OBJECTIVES: To examine the prevalence, risk factors and
      clinical characteristics of AECOPD patients with VTE. METHODS: We performed this
      multi-center, prospective, observational study that involved 16 hospitals in
      China. Patients admitted to hospital due to AECOPD were consecutively enrolled.
      Baseline characteristics, VTE risk factors, symptoms, signs and auxiliary
      examination results were collected. Lower limb venous ultrasound and computed
      tomography pulmonary angiography were examined. RESULTS: Between June 2009 and
      October 2010, a total of 1144 AECOPD patients (the average age 72.0 +/- 9.1
      years, 761 males) were enrolled in this study. Seventy-eight (6.8%) were
      diagnosed with VTE, including 24 PE, 64 DVT, 10 combined PE and DVT. VTE patients
      were older than non-VTE patients. History of venous thromboembolism and lower
      extremity varicose vein, and presence of longer immobility (>=3 days), lower
      limbs problems of swelling, pain and walking difficulties, diuretics use, fever,
      syncope, higher d-dimer and lower hemoglobin were more common in VTE patients
      than in non-VTE patients. After adjusting the covariates, venous thrombosis
      history, prolonged immobility (>=3 days), lower limb pain before hospitalization,
      higher d-dimer independently associated with VTE development. Regular
      glucocorticoid use was not associated with increased risk of VTE in this set of
      patients. CONCLUSION: VTE is relatively common among hospitalized AECOPD
      patients. Conventional prophylactic anticoagulant therapy may be considered for
      those hospitalized AECOPD patients with risk factors.

PMID- 30207644
TI  - Unilateral Cauliflower Ear due to Leprosy or Trauma - A Diagnostic Challenge.
AB  - The terminology Cauliflower ear refers to the appearance of external ear,
      sequelae to underlying primary inflammation/infection. Trauma and secondary
      infection or perichondritis being the most common cause of cauliflower ear, this
      article describes a case of unilateral cauliflower ear due to multibacillary
      leprosy. This case shows the importance of skin smears and the histopathological
      identification and classification of leprosypatients with unusual lesions.

PMID- 30207645
TI  - Bezafibrate in Primary Biliary Cholangitis.

PMID- 30207646
TI  - [Contents and the Correlations of the Total Anthocyanins and Saponins of the
      Vegetative Organs of Panax notoginseng with Purple and Green Aerial Stems at
      Different Growth Stages].
AB  - Objective: To study the accumulation characteristics of total anthocyanins and
      saponins in the vegetative organ of Panax notoginseng with purple and green
      aerial stems at different growth stages. Methods: The contents of the total
      anthocyanins and saponins of the leaves, aerial stems, rhizomes and the
      adventitious roots of one-, two- and three-year-old Panax notoginseng with purple
      and green aerial stems were determined by spectrophotometry. Results: From one
      year-old to three-year-old Panax notoginseng, the total anthocyanin contents
      (TACs) of the leaves, aerial stems and all vegetative organs and the percentages
      of the aerial stems TACs to those of all vegetative organs of purple aerial
      stemmed Panax notoginseng plants, the percentages of the total saponin contents
      (TSCs) of the leaves and aerial stems to those of all vegetative organs of the
      purple and green aerial stemmed plants and the percentages of the leaves TACs to
      those of vegetative organs of the green aerial stemmed plants all decreased. The
      TACs of the leaves and all vegetative organs of the green aerial stemmed plants,
      the TACs of the rhizomes and their adventitious roots, the vegetative organ TSCs
      and the percentages of the TSCs of the rhizomes and their adventitious roots to
      those of all vegetative organs of the purple and green aerial stemmed plants, and
      the percentages of the TACs of the rhizomes and their adventitious roots to those
      of all vegetative organs of the purple aerial stemmed plants were increased. The
      increasing rates of the TACs of the aerial stems and all vegetative organs and
      the TSCs of the aerial stems, rhizomes and their adventitious roots and all
      vegetative organs of the purple aerial stemmed plants were always higher than
      those of the green aeria stemmed plants, but the increasing rates of the leaves
      TSCs were lower than those of the green aerial stemmed plants, and the content
      changes of the vegetative organ TACs and TSCs of the purple and green aerial
      stemmed plants exhibited different correlations. Additionally, the three-years
      old plants, the TSCs of the vegetative organs of the purple aerial stemmed plants
      were all higher than those of the green aerial stemmed plants, but the TACs of
      the leaves and rhizomes and their adventitious roots were lower than those of the
      green aerial stemmed plants. Conclusion: The saponin-accumulating capacity of the
      vegetative organs of purple aerial stemmed Panax notoginseng plants is stronger
      than that of green aerial stemmed Panax notoginseng.

PMID- 30207647
TI  - [Cultivation and Standardized Technology Research on A New Astragalus Variety of
      Longqi 4].
AB  - Objective: To breed a new Astragalus variety and to study its standard
      cultivation techniques, which are high yield, good quality, disease resistance,
      anti-reverse with intrinsic quality in line with the standard of the
      Pharmacopoeia of the People' s Republic of China. Methods: By using the method of
      single plant selection,15 excellent individual plants were selected in 2003->seed
      period tested in 2004->strains identification tested from 2005 to 2007 -> new
      strains comparison tested for HQZX04-04-01 in medicine period from2008 to 2010
      >regional tested and production demonstration for HQZX04-04-01 from 2011 to 2014
      >Longqi 4 was named by Crop Variety Approval Committee of Gansu Province in
      April,2015. Results: A new Astragalus variety of Longqi 4( the original code
      HQZX04-04-01) was bred. By 3 n tests in different ecological zones, the average
      yield of fresh Astragalus root was 708. 9 kg /666. 7 m2,and was31. 1% increased
      compared with the control variety; special / first class rate was 21. 5%,30.
      6%,in which were 4. 8,5. 3 percentage points higher than that of the control
      variety, respectively; root rot disease incidence and disease index were 25.
      7%,13. 5%,in which were 2. 75,2. 17 percentage points reduced compared with
      control variety; intrinsic quality were as follows, the total ash was 4. 5%,the
      extract was 41. 0%,the content of calycosin was 0. 10%,and the content of
      astragaloside was 0. 076%,respectively,which superior than the 2010 edition of
      the standard of the Pharmacopoeia of the People' s Republic of China. Conclusion:
      A new Astragalus variety of Longqi 4 is high-yield, good-quality, disease
      resistant, anti-inverse and its intrinsic quality in lines with the standard of
      the Pharmacopoeia of the People's Republic of China. Longqi 4 is suitable for
      application at an altitude of 1 900 ~ 2 400 m, the annual average temperature of
      5 ~ 8 C,semi-arid and cold damp ecological area of annual precipitation of 450 ~
      550 mm.

PMID- 30207648
TI  - [Effect of Different Locations and Genotypes on Yield and Accumulation of
      Bioactive Constituents in Salvia miltiorrhiza].
AB  - Objective: The root yield and active constituent contents were analyzed from four
      Salvia miltiorrhiza cultivars grown at three different locations( Zhuyang,
      Changqing, and Taian, Shandong Province) to determine the influence of
      environmental conditions and cultivars. . Methods: Phenolic acids and tanshinones
      were analyzed by HPLC method. Total phenolic acids content were analyzed by
      FolinCiocalteu method. Klason method was used to determine the content of lignin.
      Results: The root yield and the active constituent contents were significantly
      affected by different environments and cultivars of Salvia miltiorrhiza. The root
      yield was negatively correlated with active constituent contents. Salvia
      miltiorrhiza of Zhuyang location had the highest active constituent content, but
      it had the lowest root yield. Salvia miltiorrhiza of Taian location had the
      lowest active constituent contents, while it had the highest root yield. Salvia
      miltiorrhiza of Changqing location had relatively higher bio-yields of phenolic
      acids and tanshinones, which made it suitable for Salvia miltiorrhiza
      cultivation. Furthermore, compared with three other cultivars,105 cultivar could
      remain the salvianolic acid B stable, which indicating that 105 cultivar was
      possible related to resistances. Conclusion: The research provides a theoretical
      basis for the selecting of the optimal cultivar and the optimal environmental
      condition.

PMID- 30207649
TI  - [Identification of Original Species of Fish Maw by DNA Barcoding].
AB  - Objective: To identify the original species of fish maw sold in Guangzhou market
      by DNA barcoding technology. Methods: Mitochondrial cytochrome C subunit I (CO I)
      gene fragment of eleven fish maw samples were amplified and sequenced with the
      self-designed primers. UPGMA phylogenetic tree were constructed for clustering
      analysis. The species origin of each sample was identified with the
      identification engine provided in the Barcode of Life Data Systems (BOLD).
      Results: The self-designed primers were effective in fish maw CO I amplification
      and sequencing, with success rates both of 100%. BOLD identification and UPGMA
      clustering analysis indicated the fish maw samples were derived from five fish
      species of three families. Conclusion: DNA barcoding combined with BOLD
      identification system can accurately identify the species origin of commercial
      fish maw.

PMID- 30207650
TI  - [Sodium Selenite Regulates Growth and Uptake of Se,As and Heavy Metals of
      Trillium tschonoskii].
AB  - Objective: To study the influence of different concentrations of selenium on the
      growth and absorbing of Se,Cd,Pb,Hg and As in Trillium tschonoskii. Methods:
      Trillium tschonoskii was treated with different concentrations of exogenous
      selenium, arsenic and heavy metals,and then the mass growth, leaf area,root
      number and other indicators reflecting its growth rule were calculated. Atomic
      fluorescence method was used to measure the absorption contents of Se,Cd,Pb,Hg
      and As. Results: The relative mass growth,leaf area and root number of Trillium
      tschonoskii increased at first and then decreased with the increasing of
      exogenous selenium concentrations. When the concentration of selenium was 25 mg /
      kg,the relative mass growth,leaf area and root number of Trillium tschonoskii
      reached a maximum. When selenium concentrations was over than 30 mg / kg,it
      inhibited the growth and development of Trillium tschonoskii. Trillium
      tschonoskii absorbing Cd,Pb,Hg and As had a regular of first decreasing then
      increasing and last decreasing. It reached the lowest when selenium
      concentrations at the range of 10 ~ 15 mg / kg. . Conclusion: Selenium had both
      stimulating effect and inhibiting effect on the growth and development of
      Trillium tschonoskii. Different selenium concentrations have different effects in
      absorbing Cd,Pb,Hg and As of Trillium tschonoskii

PMID- 30207651
TI  - [Metabolism Changes of Main Active Ingredients During Liquid Fermentation of
      Cordyceps militaris].
AB  - Objective: To study the accumulation and changes of main active ingredients
      during liquid fermentation of Cordyceps militaris. Methods: The militaris varity
      GIM5. 270 was selected to extended fermentation time to 20 days on the basic
      fermentation condition. Meanwhile, the accumulation and dynamic changes of
      biomass, polysaccharide, cordycepic acid, adenosine and cordycepin in the
      fermentation system were detected by the analytical method of contents per 24
      hour. Results: The foundation culture medium composed of complex nitrogen sources
      could reach a higher biomass level than single nitrogen sources. In addition,
      with the development of time, the mycelial biomass increased, the contents of
      polysaccharide and cordycepic acid( D-mannitol) increased firstly and then
      decreased, the contents of adenosine decreased gradually and cordycepin( 3-deoxy
      adenosine) increased gradually. Conclusion: The whole system is observed
      autolyzed phenomenon caused by absorbing self-generated nutrients. In this study,
      the dynamic changes of the main active ingredients in the fermentation system are
      researched and the optimum collecting time is determined, which provides evidence
      for reaching a better yield of the active ingredients.

PMID- 30207652
TI  - [Cloning of beta-actin Gene in Psammosilene tunicoides and Its Role as a
      Reference Gene].
AB  - Objective: To establish a real-time quantitative PCR method to detect
      Psammosilene tunicoides beta-actin, and to provide a reference gene for the
      detection of Psammosilene tunicoides genes by q PCR. Methods: Specific primers
      were designed based on the conserved region of the beta-actin gene( Gen Bank) and
      were used to amplify beta-actin by PCR. beta-actin was also used as a reference
      gene in the q PCR analysis of glycosyltransferase gene( UGT) expression in the
      roots,stems,and leaves of Psammosilene tunicoides. Results: The length of the
      beta-actin gene amplicon from Psammosilene tunicoides was 153 bp and shared
      relatively high homology with beta-actin found in Vaccaria segetalis, Myosoton
      aquaticum and Portulaca oleracea. Furthermore, UGT was revealed to be stably
      expressed in different Psammosilene tunicoides tissues when beta-actin was
      employed as the reference gene. Conclusion: beta-actin is a reliable and suitable
      reference gene for studies on the expression of triterpenoid saponin biosynthesis
      related genes in Psammosilene tunicoides.

PMID- 30207653
TI  - [Identification on Five Kinds of Easily Confused Bupleurum Medicinal Materials].
AB  - Objective: Macroscopic identification, thin layer chromatography( TLC)
      identification and molecular identification based on the Chinese Pharmacopoeia
      were established to identify five kinds of Bupleurum medicinal materials such as
      Bupleurum chinense,Bupleurum scorzonerifolium, Bupleurum marginatum, Bupleurum
      marginatum var. stenophyllum and Bupleurum bicaule,which were easily confused.
      Methods: According to the Chinese Pharmacopoeia,macroscopic characters of these
      five kinds of Bupleurum medicinal materials were observed and described; TLC
      identification method with saikosaponin d and control medicinal material of
      Bupleuri Radix as reference substances was established. Furthermore, DNA barcode
      was applied in identification of these confused drugs. Results: Five Bupleurum
      medicinal materials could be easily distinguished by their morphological
      characters. Moreover, TLC of Bupleurum chinense,Bupleurum scorzonerifolium,
      Bupleurum marginatum and Bupleurum marginatum var. stenophyllum were extremely
      similar while being different from that of Bupleurum bicaule. The ITS2 sequences
      could be used to identify the five Bupleurum medicinal materials. Conclusion: The
      established macroscopic identification and TLC for distinguishing of the five
      kinds of Bupleurum medicinal materials are simple and accurate while DNA barcode
      technology being effective and extensive. Besides, this study provides scientific
      basis for the further pharmacodynamic studies on Bupleurum marginatum and
      Bupleurum marginatum var. stenophyllum.

PMID- 30207654
TI  - [Correlation of Agronomic Character of Panax notoginseng in Guangxi with Soil
      Physical and Chemical Properties].
AB  - Objective: To study the effect of physicochemical characteristics of soil on
      Panax notoginseng agronomic character, in order to offer the theory for selecting
      an appropriate soil to cultivate Panax notoginseng, and to build the production
      bases. Methods: To test and analyze Panax notoginseng agronomic character, to
      analyze the form of layered soil particles, p H value and soil fertility. At the
      same time, the analysis of Panax notoginseng plant height, leaf number, the
      length of taproot, the width of taproot, stem diameter, the width of residual
      part of stem, rootlet number, root fresh and dry weight and drying rate were
      carried out. Results: Panax notoginseng agronomic character had a large
      difference. The length of roots, the width of roots and a large number of
      rootlets had a promoting effect on accumulating biological yield. Nevertheless,
      the numbers of branches had no obvious impact on accumulating biological yield.
      Most of soil texture were silty clay or light clay of silty clay. Physical clay
      and coarse silt could promote the growth of Panax notoginseng. Sand grain had
      significant effect on Panax notoginseng growth. A reasonable use of nitrogenous
      fertilizer had a prominent promoting effect on the width of the medicine's root.
      In fact, the use of phosphorus potassium also had a great impact on Panax
      notoginseng growth. Conclusion: Panax notoginseng should be planted on the light
      clay which are loose and can irrigate and drain conveniently and contains many
      silty. The heavy clay soil which are defective aeration and contain cosmid has a
      bad influence of the growth of Panax notoginseng. It will cause a decrease of the
      yield of medicinal materials. Using nitrogenous fertilizer aptly also is an
      effective way to improve the quality and yield of Panax notoginseng.

PMID- 30207655
TI  - [Analysis of Volatile Components and Special Aroma in Fresh Roots of Codonopsis
      Radix].
AB  - Objective: To analyze volatile components and special aroma in fresh roots of
      Codonopsis Radix. Methods: Volatile components in fresh Codonopsis Radix origined
      from three plant sources were analyzed by HS-GC-MS, and n-hexanal, 2-hexenal and
      n-hexanol were quantified by HS-GC. Results: 64 constituents have been identified
      in Codonopsis Radix,which containing ten alcohol,20 aldehyde,14 terpene, three
      ketone, four ester, four furan, three acid, one olefin, one alkane, two sulfide
      and two other compounds. The total percentage of n-hexanal,2-hexenal and n
      hexanol was large, which were the main volatile compounds in Codonopsis Radix.
      The content of n-hexanal in Lu Dangshen, Baitiao Dangshen, Wen Dangshen, Feng
      Dangshen and Banqiao Dangshen were 54. 89%,59. 01%,55. 07%,42. 42% and 56.
      74%,which were the major volatile component contributing to special aroma in
      Codonopsis Radix. 61 compounds have been identified in Lu Dangshen including 8
      specific compounds. An external calibration method was established for
      simultaneous determination of n-hexanal,2-hexenal and hexanol in Codonopsis
      Radix. The results showed that all calibration curve three volatile components
      exhibited good linearity at a range of concentrations( R2>=0. 9995). The
      recoveries of n-hexanal, 2-hexenal and hexanol were 100. 1%,94. 8% and 112.
      6%,and the RSD were 4. 4%,8. 7% and 8. 1%,respectively. The analysis suggested
      that the content of n-hexanal in Lu Dangshen was 200. 41 MUg / g and
      significantly higher than that in Banqiao Dangshen, Wen Dangshen and Feng
      Dangshen while similar to Baitiao Dangshen. The content of hexanol in three-year
      old Lu Dangshen was significantly higher than that in twoyear-old Lu Dangshen.
      Conclusion: The present research indicates that special aroma is an important
      feature of authentic Dangshen.

PMID- 30207657
TI  - [Chemical Constituents from Przewalskia tangutica].
AB  - Objective: To study the Chemical constituents from Przewalskia tangutica.
      Methods: The compounds were isolated and identified from n-butanol extract of
      Przewalskia tangutica by various chromatographic and spectral techniques.
      Results: Twelve polar compounds were isolated and identified as scopolin(
      1),fabiatrin( 2),rutin( 3),queroetin-3-O-rutinoside-7-O-beta-D-glucopyranoside(
      4),protocatechuate( 5),vanillic acid( 6),thymine( 7),uracil( 8),cytosine(
      9),adenine( 10),uridine( 11) and adenosine( 12). Conclusion: Compounds 3 ~ 5,8 ~
      12 are obtained from Przewalskia tangutica for the first time.

PMID- 30207658
TI  - [Chemical Constituents from Eucommia ulmoides].
AB  - Objective: To investigate the chemical constituents from the barks of Eucommia
      ulmoides. Methods: After the reflux extraction of the barks of Eucommia ulmoides
      with 95% ethanol, and the ethyl acetate part was separated and purified by
      chromatographic methods, such as silica gel, Sephadex LH-20, and ODS C18. The
      structures of isolated compounds were elucidated with modern spectral methods.
      Results: Five lignanoids and three phenylpropanoids were isolated from Eucommia
      ulmoieds, which were confirmed as cycloolivil (1), (7R, 8S, 8'R)-4, 9, 4', 8'
      tetrahydroxy-3, 3'-dimethyoxyl-7, 9'-monoepoxy lignan (2), erythro-guaiacyl
      glycerol-beta-coniferyl aldehyde ether (3), pinonesinol (4), 8-hydroxypinoresinol
      (5), C-veratroylglycol (6), beta-hydroxyl-3-methoxyl-4-hydroxyacetophenone (7)
      and 3-hydroxy-4-methoxycinnamaladehyde (8). Conclusion: Compounds 5-8 are
      isolated from this plant for the first time.

PMID- 30207659
TI  - Safe Footwear Improves Worker Outcomes: OSHA- and ASTM-compliant footwear
      prevents workplace injuries.

PMID- 30207660
TI  - Buying Fall Protection Equipment in 2017.

PMID- 30207661
TI  - Suspension Trauma:Those writing fall protection plans must understand the hazards
      of harness hang syndrome in fall protection.

PMID- 30207662
TI  - Too Little Focus on ROI: The Society for Incentive Travel Excellence's SITE Index
      2017 sheds light on incentive users' tracking of return on investment (ROI)-or
      their lack of tracking.

PMID- 30207663
TI  - Summing Up 2016: The Zika virus was a concern throughout 2016, and November
      voting showed a clear trend toward broad legalization of marijuana in the United
      States.

PMID- 30207664
TI  - Cost-effectiveness of new and emerging treatment options for the treatment of
      metastatic colorectal cancer.
AB  - Cancer of the colon and rectum is now the third most common form of cancer in the
      United States in both women and men. Approximately 21% of patients with
      colorectal cancer (CRC) are diagnosed with metastatic spread upon initial
      presentation, and 50% to 60% of all patients with earlier stage CRC will
      eventually develop metastases. Advances in systemic therapies have improved
      overall survival for patients with metastatic CRC (mCRC), but with an increasing
      cost burden on the healthcare system. Patterns of treatment choice and resulting
      medical care usage and costs can differ depending on patient-specific
      characteristics, impacting overall patient care and healthcare usage. The
      economic burden associated with CRC and its management is affected by several
      factors, including stage of disease at diagnosis, patient age, time period
      studied, oncologic therapy choice, and point of view. Available data assessing
      cost impact have recently been emerging; however, they are complex to interpret
      given the substantial heterogeneity among study population and the types and
      duration of analyses.

PMID- 30207665
TI  - The evolution of biomarkers to guide the treatment of metastatic colorectal
      cancer.
AB  - In the United States, colon cancer is one of the leading causes of death and
      cancer-related death. There is a critical need to improve clinical outcomes in
      patients with metastatic colorectal cancer (mCRC), as current survival rates are
      unsatisfactory. There have been significant advances in the treatment of mCRC
      over the past decade. Molecular characteristics of mCRC and identification of
      mutations can serve predictive and prognostic indicators of disease response to
      treatment. These biomarkers can be incorporated into clinical decision making
      when developing an individualized treatment plan. Targeted therapies have
      improved the survival of patients with mCRC. As we learn about the various
      molecular alterations in this disease, additional emerging therapies can be
      developed to improve clinical outcomes in patients with mCRC.

PMID- 30207667
TI  - Data: Transforming Your Work Site: The benefits of leveraging data for on-site
      workers' protection, as well as a company's operations, must be realized.

PMID- 30207668
TI  - The Significance of API RP 2219 Recommendations in the BLSR Accident, Part 1:
      Employers and workers need to pay special attention to minimum recommended safety
      requirements of approved standards and safe working procedures.

PMID- 30207670
TI  - Amyotrophic lateral sclerosis: disease state overview.
AB  - Amyotrophic lateral sclerosis (ALS) is a disease that results in the progressive
      deterioration and loss of function of the motor neurons in the brain and spinal
      cord, leading to paralysis. ALS affects approximately 16,000 individuals, with a
      prognosis for survival of 2 to 5 years. There are 2 types of ALS differentiated
      by genetics: familial and sporadic (idiopathic). Diagnosis is determined by
      excluding other conditions and utilizing clinical examinations, laboratory tests,
      and nerve conduction/electromyography studies. Due to the collection of
      information from the participation of patients with ALS in registries, biomarkers
      and genes associated with ALS have been discovered. The best practices for the
      management of ALS include an interdisciplinary approach aimed at addressing the
      physical and psychological needs and desires of patients and their families and
      caregivers.

PMID- 30207669
TI  - Emergency Response is a Matter of Time: The best time to prepare a facility's
      immediate and effective response to hazardous chemical exposure is before it ever
      happens.

PMID- 30207671
TI  - Disease-modifying treatment of amyotrophic lateral sclerosis.
AB  - Currently, there is no cure for amyotrophic lateral sclerosis (ALS) and the
      foundation of ALS management revolves around symptomatic and palliative care.
      Early diagnosis offers the best prognosis for a longer, quality life while living
      with the disease. Many medications are used to relieve symptoms but there are
      only 2 pharmacologic agents indicated for the management of ALS. For 2 decades,
      riluzole had been the mainstay of disease-modifying therapy, but in 2017,
      edaravone became the second agent approved in the management of patients with
      ALS. The mechanism of either agent is not well known. Riluzole is thought to
      reduce damage to motor neurons through an inhibitory effect on glutamate release,
      while edaravone is thought to act as a neuroprotective agent that prevents
      oxidative stress damage as a free radical scavenger. With the lack of treatment
      options, it is imperative for healthcare professionals to understand the nuances
      of using these 2 agents to optimize therapy and quality of life for patients with
      ALS.

PMID- 30207672
TI  - ALS managed care considerations.
AB  - As a chronic neurological disorder characterized by the progressive deterioration
      of neuromuscular function, amyotrophic lateral sclerosis (ALS) renders
      significant physical, psychological, and emotional tolls on patients, their
      families, and caregivers. Coupled with and contributing to the severe impact on
      quality of life are the substantial economic costs, which can be direct and
      indirect, and personal as well as societal. Understanding the magnitude and
      specifics of the costs accompanying ALS will provide useful perspectives to
      pharmacists who treat patients with ALS.

PMID- 30207673
TI  - Hazard Communication Program - Training is the Key: Employees are to be trained
      when they are initially assigned to work with a hazardous chemical. Additional
      training is to be done whenever a new health or physical hazard is introduced
      into the work area.

PMID- 30207674
TI  - Seeing Safety Differently: Remote operated cameras aid in mitigating risk in
      construction work.

PMID- 30207675
TI  - Using State-of-the-Art Technology: Without mass notification systems, the silence
      can be deafening and fatal.

PMID- 30207676
TI  - Oxygen Vacancy Defects Boosted High Performance p-Type Delafossite CuCrO2 Gas
      Sensors.
AB  - p-type ternary oxides can be extensively explored as alternative sensing channels
      to binary oxides with diverse structural and compositional versatilities. Seeking
      a novel approach to magnify their sensitivities toward gas molecules, e.g.,
      volatile organic compounds (VOCs), will definitely expand their applications in
      the frontier area of healthcare and air-quality monitoring. In this work,
      delafossite CuCrO2 (CCO) nanoparticles with different grain sizes have been
      utilized as p-type ternary oxide sensors. It was found that singly ionized oxygen
      vacancies (Vo*) defects, compared with the grain size of CCO nanoparticles, play
      an important role in enhancing the charge exchange at the VOCs molecules/CCO
      interface. In addition to suppressing the hole concentration of the sensor
      channel, the unpaired electron trapped in Vo* provides an active site for
      chemisorptions of environmental oxygen and VOCs molecules. The synergetic effect
      is responsible for the observed increase of sensitivity. Furthermore, the
      sensitive (Vo* defect-rich) CCO sensor exhibits good reproducibility and
      stability under a moderate operation temperature (<325  degrees C). Our work
      highlights that Vo* defects, created via either in situ synthesis or
      postannealing treatment, could be explored to rationally boost the performance of
      p-type ternary oxide sensors.

PMID- 30207677
TI  - Self-Powered and Highly Efficient Production of H2O2 through a Zn-Air Battery
      with Oxygenated Carbon Electrocatalyst.
AB  - Industrially producing H2O2 consumes lots of energy and generates byproducts. For
      the first time, we demonstrate the non-energy-consuming, self-powered production
      of H2O2 based on a Zn-air battery with oxygenated carbon electrocatalyst. The
      battery with power density of 360 W mgeo-2 at a operating voltage of 0.8 V
      exhibited high H2O2 production rate of 5.93 mol mgeo-2 h-1. By tuning the ratio
      of the oxygen-containg groups, the origin of the high activity was investigated.
      Combining the DFT calculations, we found that C-O-C and -CHO contribute more to
      the H2O2 production compared to other functional groups.

PMID- 30207678
TI  - Polymeric Micelles Based on Light-Responsive Block Copolymers for the
      Phototunable Detection of Mercury(II) Ions Modulated by Morphological Changes.
AB  - Polymeric micelles based on light-responsive block copolymers were prepared and
      used for the phototunable detection of mercury(II) ions. 2-Nitrobenzyl acrylate
      (NBA) and ( E)-2-((4-((4-formylphenyl)diazenyl)phenyl)(methyl)amino) ethyl
      acrylate (FPDEA) were copolymerized from a poly(ethylene oxide) (PEO)
      macroinitiator via atom transfer radical polymerization (ATRP), leading to a well
      defined block copolymer of PEO113- b-[p(NBA10- co-FPDEA3)] with a low
      polydispersity index (PDI = 1.16). After polymerization, the aldehyde groups of
      PEO- b-[p(NBA- co-FPDEA)] were converted to aldoxime groups by reacting with
      hydroxylamine, leading to the formation of a final oxime-containing polymeric
      probe, PEO- b-[p(NBA- co-HPDEA)], P1. The resulting block copolymer, P1, was self
      assembled in water to yield spherical micelles that consist of a PEO block
      forming a hydrophilic shell and a copolymer of light-responsive NBA and a
      mercury(II) ion-detecting HPDEA block forming a hydrophobic core. Upon the
      addition of mercury(II) ions to this micellar solution, no detection was observed
      since water-soluble mercury(II) ions have limited accessability to the oxime
      units of P1, which are located in the hydrophobic core. After UV light
      irradiation, however, the photolabile 2-nitrobenzyl moieties were cleaved, and
      hydrophobic PNBA was transformed to hydrophilic poly(acrylic acid) (PAA), leading
      to the photoinduced dissociation of micelles to unimers. As a result, the oxime
      units of P1 were exposed to a hydrophilic environment and could react with
      mercury(II) ions to form nitrile groups, resulting in the turn-on detection of
      mercury(II) ions by UV light irradiation.

PMID- 30207679
TI  - Boosting Transport Distances for Molecular Excitons within Photoexcited Metal
      Organic Framework Films.
AB  - Herein, we describe the fabrication of porphyrin-containing metal-organic
      framework thin films with 1,4-diazabicyclo[2.2.2]octane (DABCO) pillaring linkers
      and investigate exciton transport within the films. Steady-state emission
      spectroscopy indicates that the exciton can traverse up to 26 porphyrin layers
      when DABCO is used as a pillaring linker, whereas on average only 9-11 layers can
      be traversed when either 4,4'-bipyridine (a pillaring linker) or pyridine (a
      nonpillaring, layer-interdigitating ligand) is used. These results can be
      understood by taking into account the decreased separation distances between
      transition dipoles associated with chromophores (porphyrins) sited in adjacent
      layers. Shorter distances translate into faster Forster-type exciton hopping and,
      therefore, more hops within the few nanosecond lifetime of the porphyrin's
      singlet excited-state. The findings have favorable implications for the
      development of MOF-based photoelectrodes and photoelectrochemical energy
      conversion devices.

PMID- 30207680
TI  - Multifunctional Nanoparticles Enable Efficient Oral Delivery of Biomacromolecules
      via Improving Payload Stability and Regulating the Transcytosis Pathway.
AB  - In oral delivery of biomacromolecules, ligand-modified nanoparticles (NPs) have
      emerged as a promising tool to improve the epithelial uptake of the loaded
      protein/peptide. Unfortunately, the stability and the transport mechanisms of the
      biotherapeutics during the intracellular transportation still remained unclear,
      leading to the poor transepithelial efficiency. Additionally, developing novel
      approaches to simultaneously monitor the payload bioactivity during the transport
      processes is veritably benefit for keeping their bioactivity. In the present
      study, EGP peptide (KRKKKGKGLGKKRDPCLRKYK), a ligand with high affinity to
      heparan sulfate proteoglycans (HSPGs), was found remarkably increasing the
      cellular uptake (4.5-fold) and also surprisingly achieving high transcytosis
      efficiency (4.2-fold) of poly(lactide- co-glycolide) NPs on Caco-2 cell
      monolayer. Compared with unmodified NPs (C NPs), EGP modified NPs (EGP NPs)
      exhibited more desirable colloidal stability within epithelia. In the subsequent
      study, the bioactivity of encapsulated insulin during the cellular transportation
      was innovatively monitored by a glucose consumption assay. Inspiringly, EGP NPs
      could mostly retain the bioactivity of loaded insulin whereas insulin from INS-C
      NPs was significantly degraded. Then the detailed mechanism study revealed that
      the binding of EGP to HSPGs played a vital role on NP transportation. Unlike C
      NPs being delivered in the endo/lysosomal pathway, EGP NPs were involved in
      caveolae-mediated transport, which contributes to the efficient avoidance of the
      lysosomal entrapment and sequentially facilitates the direct apical-to
      basolateral transcytosis. The enhanced absorption of EGP NPs was confirmed in in
      situ intestinal loop models. Most importantly, oral administrated INS-EGP NPs
      generated a strong hypoglycemic response on diabetic rats with 10.2-fold and 2.6
      fold increase in bioavailability compared with free insulin and INS-C NPs,
      respectively. The work provided an innovative strategy to monitor the payload
      bioactivity during the transport processes and proposed a novel aspect to
      increase oral bioavailability of biomacromolecules via improving payload
      stability and regulating the transcytosis pathway of nanocarriers.

PMID- 30207681
TI  - Three-Dimensional Interconnected Network Architecture with Homogeneously
      Dispersed Carbon Nanotubes and Layered MoS2 as a Highly Efficient Cathode
      Catalyst for Lithium-Oxygen Battery.
AB  - The structure and catalytic activity of the oxygen electrode determine the
      overall electrochemical performance of lithium-oxygen (Li-O2) batteries. Here, a
      three-dimensional (3D) porous interconnected network structure combined with
      ultrathin MoS2 nanosheets with homogeneously dispersed CNTs (MoS2/CNTs) was
      synthesized via a one-step hydrothermal reaction. The 3D interconnected
      architecture can efficiently promote the diffusion of O2 and Li ions as well as
      impregnation of electrolyte and provide more abundant storage space for the
      accommodation of discharge products, while the incorporation of uniformly
      dispersed CNTs improves the electronic conductivity and maintains the integrity
      of the cathode structure. Therefore, the Li-O2 battery based on MoS2/CNTs
      achieves improved performance with the low overpotentials (discharge/charge
      overpotentials of approximately 0.29 and 1.05 V), a high discharge specific
      capacity of 6904 mA h g-1 at a rate of 200 mA g-1, and excellent cycling
      stability (132 cycles). Experimental studies reveal that the improved
      electrochemical performance can be ascribed to the synergistic advantages of
      electronic conductive CNTs and excellent catalytic activity of the MoS2
      nanosheets. Moreover, the unique 3D interconnected network structure can
      effectively facilitate fast charge transfer kinetics and a facile mass transport
      pathway. These encouraging performances demonstrate the metal sulfide catalyst as
      a promising catalytic material of oxygen electrodes for Li-O2 batteries.

PMID- 30207682
TI  - Preparation of Methyl Viologen-Kaolinite Intercalation Compound: Controlled
      Release and Electrochemical Applications.
AB  - This work reports the preparation of novel kaolinite nanohybrid material obtained
      by intercalation of methyl viologen (MV) in the interlayer space of kaolinite,
      using methoxykaolinite (K-M) as starting material. Characterization of the
      resulting material (K-MV) confirmed the presence of MV units in the interlayer
      space of K-M with lateral orientation, associated with a high amount of water
      molecules due to the hydrophilic nature of MV. The resulting structural formula
      of this organoclay based on thermogravimetric analysis was
      Si2Al2O5(OH)3.72(OCH3)0.28(MV)0.17(H2O)0.82. The release of MV from the K-MV
      composite was studied in order to evaluate the advantages of using this material
      for pesticide formulation with MV as active ingredient. The localization of MV in
      the interlayer space of K-M significantly slows its release in water. However,
      the interactions that retain MV in the interlayer space remain sufficiently less
      intense to ensure a complete release of MV in a relatively short time (2 h). On
      the basis of the interactions that ensure MV intercalation in methoxykaolinite, K
      M was used as electrode modifier and applied for the electrochemical
      determination of MV. The electrochemical signal of MV on the K-M modified
      electrode was 2 times more intense compared to the pristine kaolinite modified
      electrode. After optimization of experimental parameters, a sensitivity of 3.91
      MUA M-1 and a detection limit of 0.14 nM were obtained at the K-M modified
      electrode. This performance represents one of the most important reported so far
      in the literature during the electrochemical determination of MV. The sensor was
      also found very efficient for MV determination in real water systems (well,
      spring, and tap water) despite the decrease of sensitivity due to the presence of
      interfering species.

PMID- 30207683
TI  - Spectral Sensor Inspired by Cone Photoreceptors and Ion Channels without External
      Power.
AB  - In this study, we focused the mimicking of the cone photoreceptor along with ion
      channel system, which is similar to real optical system. By realizing the ion
      channel and photoreceptor based on photoresponsive material and photoelectric
      film, we achieved the wavelength-selective sensor with self-power ability. For
      the first time, we combined the photoreceptor and ion channel system without
      external power. For this, we used the channel membrane with pores coated with
      light-responsive material. We measured the sensing signals without any external
      power, because photoelectric film assists the sensitive operation of the ion
      channel system. As a result, we demonstrated a spectral ion channel sensor
      triggered by the photoelectric effect. Mimicking the slow and fast responses
      typically found in cone photoreceptor, when induced light causes photovoltaic
      effect from the pyrrole-coated polyvinylidene fluoride film, this helps to
      normally operate the ion channel system with slow and fast responses to the light
      wavelengths. Consequently, this research opens the new scientific fields to
      realize the photosensor very similar to the real vision sensory organ.

PMID- 30207684
TI  - Developing Antibacterial Nanocrystalline Cellulose Using Natural Antibacterial
      Agents.
AB  - We used hairy nanocrystalline cellulose functionalized with aldehyde groups,
      otherwise known as sterically stabilized nanocrystalline cellulose (SNCC), to
      facilitate the attachment of the antibacterial agents lysozyme and nisin.
      Immobilization was achieved using a simple, green process that does not require
      any linker or activator. X-ray photoelectron spectroscopy and Fourier transform
      infrared spectroscopy analyses showed successful attachment of both nisin and
      lysozyme onto the SNCC. The efficacy of the conjugated nanocellulose against the
      model bacteria Bacillus subtilis and Staphylococcus aureus was tested in terms of
      bacterial growth, cell viability, and biofilm formation/removal. The results show
      that the minimum inhibitory concentration of the conjugated nanocellulose is
      higher than that of lysozyme and nisin in free form, which was expected given
      that immobilization reduces the possible spatial orientations of these proteins.
      We observed that free nisin is not active against S. aureus after 24 h of
      exposure due to either deactivation of free nisin or development of resistance in
      S. aureus against free nisin. Interestingly, we did not observe this phenomenon
      when the bacteria were exposed to antibacterials immobilized on nanocellulose,
      suggesting that immobilization of antibacterial agents onto SNCC effectively
      retains their activity over long time periods. We suggest that antibacterial SNCC
      is a promising candidate for the development of antibacterial wound dressings.

PMID- 30207685
TI  - Patterning Porosity in Hydrogels by Arresting Phase Separation.
AB  - Independent control over phase separation and photo-cross-linking allows the
      structure and porosity of hydrogels to be patterned in a single photolithographic
      step. This observation is based upon a temperature-triggered spinodal
      decomposition of a ternary mixture of water, salt, and polymer into a salt-rich
      aqueous phase and a polymer-rich phase. Importantly, subsequent exposure to light
      arrests the phase separation, allowing the porosity state to be frozen in a cross
      linked hydrogel network. Tuning the delay between the application of heat and
      illumination allows the pore size to be tuned between 400 nm and 4 MUm. By
      utilizing gray-scale photomasks, a single process can be used to define regions
      of pure hydrogel, porous hydrogel with a programmed average pore size, and blank
      substrate with no hydrogel. In addition to representing a combination of top-down
      and bottom-up processes that enables the realization of complex samples, the
      simplicity of this process and the versatility of the resultant patterns could
      provide a useful capability for the definition of hydrogel samples for the
      development of advanced biomaterials.

PMID- 30207686
TI  - All Carbon Dual Ion Batteries.
AB  - Dual ion batteries based on Na+ and PF6- received considerable attention due to
      their high operating voltage and the abundant Na resources. Here, cheap and
      easily obtained graphite that served as a cathode material for dual ion battery
      delivered a very high average discharge platform (4.52 V vs Na+/Na) by using
      sodium hexafluorophosphate in propylene carbonate as electrolyte. Moreover, the
      all-carbon dual ion batteries with graphite as cathode and hard carbon as anode
      exhibited an ultrahigh discharge voltage of 4.3 V, and a reversible capacity of
      62 mAh.g-1 at 40 mA.g-1. Phase changes have been investigated in detail through
      in situ X-ray diffraction and in situ Raman characterizations. The stable
      structure provides long life cycling performance, and the pseudocapacitance
      behavior also demonstrates its benefits to the rate capability. Thus, dual ion
      batteries based on sodium chemistry are very promising to find their applications
      in future.

PMID- 30207687
TI  - Inflammatory Role of Cancer-Associated Fibroblasts in Invasive Breast Tumors
      Revealed Using a Fibrous Polymer Scaffold.
AB  - Inflammation in cancer fuels metastasis and worsens prognosis. Cancer-associated
      fibroblasts (CAFs) present in the tumor stroma play a vital role in mediating the
      cascade of cancer inflammation that drives metastasis by enhancing angiogenesis,
      tissue remodeling, and invasion. In vitro models that faithfully recapitulate CAF
      mediated inflammation independent of coculturing with cancer cells are
      nonexistent. We have engineered fibrous matrices of poly(epsilon-caprolactone)
      (PCL) that can maintain the manifold tumor-promoting properties of patient
      derived CAFs, which would otherwise require repetitive isolation and complex
      coculturing with cancer cells. On these fibrous matrices, CAFs proliferated and
      remodeled the extracellular matrix (ECM) in a parallel-patterned manner mimicking
      the ECM of high-grade breast tumors and induced stemness in breast cancer cells.
      The response of the fibroblasts was observed to be sensitive to the scaffold
      architecture and not the polymer composition. The CAFs cultured on fibrous
      matrices exhibited increased activation of the NF-kappaB pathway and downstream
      proinflammatory gene expression compared to CAFs cultured on conventional two
      dimensional (2D) dishes and secreted higher levels of proinflammatory cytokines
      such as IL-6, GM-CSF, and MIP-3alpha. Consistent with this, we observed increased
      infiltration of inflammatory cells to the tumor site and enhanced invasiveness of
      the tumor in vivo when tumor cells were injected admixed with CAFs grown on
      fibrous matrices. These data suggest that CAFs better retain their tumor
      promoting proinflammatory properties on fibrous polymeric matrices, which could
      serve as a unique model to investigate the mechanisms of stroma-induced
      inflammation in cancer progression.

PMID- 30207688
TI  - Functional Capsules via Subcomponent Self-Assembly.
AB  - Coordination-driven self-assembly can produce large, symmetrical, hollow cages
      that are synthetically easy to access. The functions provided by these
      aesthetically attractive structures provide a driving force for their
      development, enabling practical applications. For instance, cages have provided
      new methods of molecular recognition, chirality sensing, separations,
      stabilization of reactive species, and catalysis. We have fruitfully employed
      subcomponent self-assembly to prepare metal-organic capsules from simple building
      blocks via the simultaneous formation of dynamic coordinative (N->metal) and
      covalent (N?C) bonds. Design strategies employ multidentate pyridyl-imine ligands
      to define either the edges or the faces of polyhedral structures. Octahedral
      metal ions, such as FeII, CoII, NiII, ZnII, and CdII, constitute the vertices.
      The generality of this technique has enabled the preparation of capsules with
      diverse three-dimensional structures. This Account highlights how fundamental
      investigations into the host-guest chemistry of capsules prepared through
      subcomponent self-assembly have led to the design of useful functions and new
      applications. We start by discussing simple host-guest systems involving a single
      capsule and continue to systems that include multiple capsules and guests, whose
      interactions give rise to complex functional behavior. Many of the capsules
      presented herein bind varied neutral guests, including aromatic or aliphatic
      molecules, biomolecules, and fullerenes. Binding selectivity is influenced by
      solvent effects, weak non-covalent interactions between hosts and guests, and the
      size, shape, flexibility, and degree of surface enclosure of the inner spaces of
      the capsules. Some hosts are able to adaptively rearrange structurally or express
      a different ratio of cage diastereomers to optimize the guest binding ability of
      the system. In other cases the bound guest can be either protected from
      degradation or catalytically transformed through encapsulation. Other capsules
      bind anions, most often in organic solvents and occasionally in water.
      Complexation is usually driven by a combination of electrostatic interactions,
      hydrogen bonding, and coordination to additional metal centers. Anion binding can
      also induce cage diastereomeric reconfiguration in a similar manner to some
      neutral guests, illustrating the general ability of subcomponent self-assembled
      capsules to respond to stimuli due to their dynamic nature. Capsules have been
      developed as supramolecular extractants for the selective removal of anions from
      water and as channels for transporting anions through planar lipid bilayers and
      into vesicles. Different capsules may work together, allowing for functions more
      complex than those achievable within single host-guest systems. Incorporation of
      stimuli-responsive capsules into multicage systems allows individual capsules
      within the network to be addressed and may allow signals to be passed between
      network members. We first present strategies to achieve selective guest binding
      and controlled guest release using mixtures of capsules with varied affinities
      for guests and different stabilities toward external stimuli. We then discuss
      strategies to separate capsules with encapsulated cargos via selective phase
      transfer, where the solvent affinities of capsules change as a result of anion
      exchange or post-assembly modification. The knowledge gained from these multicage
      systems may lead to the design of synthetic systems that can perform complex
      tasks in biomimetic fashion, paving the way for new supramolecular technologies
      to address practical problems.

PMID- 30207689
TI  - Cascaded Aptamers-Governed Multistage Drug-Delivery System Based on Biodegradable
      Envelope-Type Nanovehicle for Targeted Therapy of HER2-Overexpressing Breast
      Cancer.
AB  - Tumor-specific therapeutic platforms with improved targeting efficacy and
      minimized side effect are crucial in cancer therapy. Capitalizing on the
      recognition capability and biocompatibility of aptamers, we herein designed a
      multistage targeted drug-delivery system using multiple biodegradable molecules
      enveloped nanovehicle that can be employed to efficiently treat human epithelial
      growth factor receptor (HER2)-overexpressing breast cancer. In this nanovehicle,
      two aptamers respectively specific to HER2 and ATP were organized in a
      hierarchical manner. The outmost HER2 aptamer (HB5) governs the recognition to
      HER2 protein overexpressed in SK-BR-3 cell lines, while the ATP aptamer
      incorporated with anticancer drug (-)-epigallocatechin gallate (EGCG) and
      protamine sulfate in the inner core functions as a switch of drug release in
      response to abundant intracellular ATP. The targeting and drug locker aptamers
      were cascaded for active targeting effect and stimuli responsiveness,
      guaranteeing the site-specific drug transportation and endogenous species
      triggered drug release inside the tumor cells. Moreover, nanostructured lipid
      carriers (NLCs) were constructed to wrap and stabilize the loosely bounded
      ternary complex, minimizing premature drug leakage potentially encountered by the
      biomolecule assembled nanocarriers. This multiple biomolecules-enveloped
      nanovehicle demonstrated improved inhibitory actions on tumor growth and minimum
      side effect to normal organs and tissues both in vitro and in vivo. The presented
      nanovehicle built from recognition and therapeutic components in a nontoxic
      framework offered a promising drug-delivery platform with transport precision and
      biological safety.

PMID- 30207690
TI  - Two-Dimensional Ti3C2 MXene for High-Resolution Neural Interfaces.
AB  - High-resolution neural interfaces are essential tools for studying and modulating
      neural circuits underlying brain function and disease. Because electrodes are
      miniaturized to achieve higher spatial resolution and channel count, maintaining
      low impedance and high signal quality becomes a significant challenge.
      Nanostructured materials can address this challenge because they combine high
      electrical conductivity with mechanical flexibility and can interact with
      biological systems on a molecular scale. Unfortunately, fabricating high
      resolution neural interfaces from nanostructured materials is typically expensive
      and time-consuming and does not scale, which precludes translation beyond the
      benchtop. Two-dimensional (2D) Ti3C2 MXene possesses a combination of remarkably
      high volumetric capacitance, electrical conductivity, surface functionality, and
      processability in aqueous dispersions distinct among carbon-based nanomaterials.
      Here, we present a high-throughput microfabrication process for constructing
      Ti3C2 neuroelectronic devices and demonstrate their superior impedance and in
      vivo neural recording performance in comparison with standard metal
      microelectrodes. Specifically, when compared to gold microelectrodes of the same
      size, Ti3C2 electrodes exhibit a 4-fold reduction in interface impedance.
      Furthermore, intraoperative in vivo recordings from the brains of anesthetized
      rats at multiple spatial and temporal scales demonstrate that Ti3C2 electrodes
      exhibit lower baseline noise, higher signal-to-noise ratio, and reduced
      susceptibility to 60 Hz interference than gold electrodes. Finally, in neuronal
      biocompatibility studies, neurons cultured on Ti3C2 are as viable as those in
      control cultures, and they can adhere, grow axonal processes, and form functional
      networks. Overall, our results indicate that Ti3C2 MXene microelectrodes have the
      potential to become a powerful platform technology for high-resolution biological
      interfaces.

PMID- 30207691
TI  - Honeycomb-Satellite Structured pH/H2O2-Responsive Degradable Nanoplatform for
      Efficient Photodynamic Therapy and Multimodal Imaging.
AB  - The oxygen-deprived environment of a solid tumor is still great restriction in
      achieving an efficient photodynamic therapy (PDT). In this work, we developed a
      smart pH-controllable and H2O2-responsive nanoplatform with degradable property,
      which was based on honeycomb manganese oxide (hMnO2) nanospheres loaded with Ce6
      sensitized core-shell-shell structured up-conversion nanoparticles
      (NaGdF4:Yb/Er,Tm@NaGdF4:Yb@NaNdF4:Yb) (abbreviated as hMUC). In the system, the
      speedy breakup of the as-prepared hMnO2 nanostructures results in release of
      loaded Ce6-sensitized UCNPs under the condition of H2O2 in acid solution. When
      exposed to tissue-penetrable 808 nm laser, up-conversion nanoparticles (UCNPs)
      emit higher-energy visible photons which would be absorbed by Ce6 to yield
      cytotoxic reactive oxygen species (ROS), thus triggering PDT treatment naturally.
      Moreover, the in vitro and in vivo experiments demonstrate that hMUC sample with
      the honeycomb-satellite structure can serve as multimodal bioimaging contrast
      agent for self-enhanced upconversion luminescence (UCL), magnetic resonance
      imaging (MRI) and computed tomography (CT) imaging, indicating that the as
      prepared hMUC could be used in imaging-guided diagnosis and treatment, which has
      a potential application in the PDT treatment of tumor.

PMID- 30207692
TI  - One-Pot Preparation of Mechanically Robust, Transparent, Highly Conductive, and
      Memristive Metal-Organic Ultrathin Film.
AB  - The future of 2D flexible electronics relies on the preparation of conducting
      ultrathin films of materials with mechanical robustness and flexibility in a
      simple but controlled manner. In this respect, metal-organic compounds present
      advantages over inorganic laminar crystals owing to their structural, chemical,
      and functional diversity. While most metal-organic compounds are usually prepared
      in bulk, recent work has shown that some of them are processable down to low
      dimensional forms. Here we report the one-pot preparation, carried out at the
      water-air interface, of ultrathin (down to 4 nm) films of the metal-organic
      compound [Cu2I2(TAA)] n (TAA= thioacetamide). The films are shown to be
      homogeneous over mm2 areas, smooth, highly transparent, mechanically robust, and
      good electrical conductors with memristive behavior at low frequencies. This
      combination of properties, as well as the industrial availability of the two
      building blocks required for the preparation, demonstrates their wide range
      potential in future flexible and transparent electronics.

PMID- 30207694
TI  - Chemical Dopant Engineering in Hole Transport Layers for Efficient Perovskite
      Solar Cells: Insight into the Interfacial Recombination.
AB  - Chemical doping of organic semiconductors has been recognized as an effective way
      to enhance the electrical conductivity. In perovskite solar cells (PSCs), various
      types of dopants have been developed for organic hole transport materials (HTMs);
      however, the knowledge of the basic requirements for being efficient dopants as
      well as the comprehensive roles of the dopants in PSCs has not been clearly
      revealed. Here, three copper-based complexes with controlled redox activities are
      applied as dopants in PSCs, and it is found that the oxidative reactivity of
      dopants presents substantial impacts on conductivity, charge dynamics, and solar
      cell performance. A significant improvement of open-circuit voltage ( Voc) by
      more than 100 mV and an increase of power conversion efficiency from 13.2 to
      19.3% have been achieved by tuning the doping level of the HTM. The observed
      large variation of Voc for three dopants reveals their different recombination
      kinetics at the perovskite/HTM interfaces and suggests a model of an interfacial
      recombination mechanism. We also suggest that the dopants in HTMs can also affect
      the charge recombination kinetics as well as the solar cell performance. Based on
      these findings, a strategy is proposed to physically passivate the electron-hole
      recombination by inserting an ultrathin Al2O3 insulating layer between the
      perovskite and the HTM. This strategy contributes a significant enhancement of
      the power conversion efficiency and environmental stability, indicating that
      dopant engineering is one crucial way to further improve the performance of PSCs.

PMID- 30207693
TI  - Reconstitution of Mammalian Enzymatic Deacylation Reactions in Live Bacteria
      Using Native Acylated Substrates.
AB  - Lysine deacetylases (KDACs) are enzymes that catalyze the hydrolysis of acyl
      groups from acyl-lysine residues. The recent identification of thousands of
      putative acylation sites, including specific acetylation sites, created an urgent
      need for biochemical methodologies aimed at better characterizing KDAC-substrate
      specificity and evaluating KDACs activity. To address this need, we utilized
      genetic code expansion technology to coexpress site-specifically acylated
      substrates with mammalian KDACs, and study substrate recognition and deacylase
      activity in live Escherichia coli. In this system the bacterial cell serves as a
      "biological test tube" in which the incubation of a single mammalian KDAC and a
      potential peptide or full-length acylated substrate transpires. We report novel
      deacetylation activities of Zn2+-dependent deacetylases and sirtuins in bacteria.
      We also measure the deacylation of propionyl-, butyryl-, and crotonyl-lysine, as
      well as novel deacetylation of Lys310-acetylated RelA by SIRT3, SIRT5, SIRT6, and
      HDAC8. This study highlights the importance of native interactions to KDAC
      substrate recognition and deacylase activity.

PMID- 30207695
TI  - Ion-Induced Localized Nanoscale Polymer Reflow for Three-Dimensional Self
      Assembly.
AB  - Thermal reflow of polymers is a well-established phenomenon that has been used in
      various microfabrication processes. However, present techniques have critical
      limitations in controlling the various attributes of polymer reflow, such as the
      position and extent of reflow, especially at the nanoscale. These challenges
      primarily result from the reflow heat source supplying heat energy to the entire
      substrate rather than a specific area. In this work, a focused ion beam (FIB)
      microscope is used to achieve controllable localized heat generation, leading to
      precise control over the nanoscale polymer reflow. Through the use of the
      patterning capability of FIB microscopy, dramatically different reflow
      performances within nanoscale distances of each other are demonstrated in both
      discrete periodic and continuous polymer structures. Further, we utilize a self
      assembly process induced by nanoscale polymer reflow to realize 3D optical
      devices, specifically, vertically aligned nanoresonators and graphene-based
      nanocubes. HFSS and Comsol simulations have been carried out to analyze the
      advantages of the polymer-based 3D metamaterials as opposed to those fabricated
      with a metallic hinge. The simulation results clearly demonstrate that the
      polymer hinges have a dual advantage; first, the removal of any interference from
      the transmission spectrum leading to strong and distinct resonance peaks and,
      second, the elimination of parasitic leeching of the enhanced field by the
      metallic hinge resulting in stronger volumetric enhancement. Thus, the 2-fold
      advantages existing in 3D polymer-hinge optical metamaterials can open pathways
      for applications in 3D optoelectronic devices and sensors, vibrational molecular
      spectroscopy, and other nanoscale 3D plasmonic devices.

PMID- 30207696
TI  - Production of Ready-To-Use Functionalized Sup35 Nanofibrils Secreted by
      Komagataella pastoris.
AB  - Amyloid nanofibrils are excellent scaffolds for designable materials that can be
      endowed with biotechnologically relevant functions. However, most of all
      excellent ideas and concepts that have been reported in the literature might
      never see real-world implementation in biotechnological applications. One
      bottleneck is the large-scale production of these materials. In this paper, we
      present an attempt to create a generic and scalable platform for producing ready
      to-use functionalized nanofibrils directly from a eukaryotic organism. As a model
      material, we assembled Sup35(1-61) amyloid nanofibrils from Saccharomyces
      cerevisiae decorated with the Z-domain dimer, which has a high affinity toward
      antibody molecules. To this end, Komagataella pastoris was engineered by
      inserting gene copies of Sup35(1-61) and the protein chimera Sup35(1-61)-ZZ into
      the genome. This strain has the capability to constantly secrete amyloidogenic
      proteins into the extracellular medium, where the mature functionalized fibrils
      form, with a production yield of 35 mg/L culture. Another striking feature of
      this strategy is that the separation of the fibril material from the cells
      requires only centrifugation and resuspension in saline water. The fast
      production rates, minimal hands-on time, and high stability of the assembled
      material are some highlights that make the direct assembly of functionalized
      fibrils in the extracellular medium an alternative to production methods that are
      not suitable for large-scale production of designed amyloids.

PMID- 30207697
TI  - Interaction of Uranium(VI) with alpha-Amylase and Its Implication for Enzyme
      Activity.
AB  - Because of its chemo- and radiotoxicity, the incorporation of uranium into human
      body via ingestion potentially poses a serious health risk. When ingested, the
      gastrointestinal fluids are the primary media to interact with uranium,
      eventually influencing and even determining its biochemical behavior in the
      gastrointestinal tract and thereafter. The chemical interactions between uranium
      and the components of gastrointestinal fluids are, however, poorly understood to
      date. In this study, the complexation of uranium(VI) (as the uranyl ion, UO22+)
      with the protein alpha-amylase, one of the major enzymes in saliva and pancreatic
      juices, was investigated over a wide range of pH or uranium/alpha-amylase
      concentrations covering physiological conditions. Macroscopic sorption
      experiments suggested a strong and fast complexation of UO22+ to alpha-amylase
      between pH 5 and 7. Potentiometric titration was employed to determine the
      complex stability constants for the relevant UO22+ alpha-amylase complexes, which
      is crucial for reliable thermochemical modeling to assess the potential health
      risk of uranium. Extended X-ray absorption fine structure (EXAFS) spectroscopy
      revealed that alpha-amylase is interacting with UO22+ primarily via its
      carboxylate groups presumably from the aspartic acid and glutamic acid side
      chains. The effect of UO22+ on the enzyme activity was also investigated to
      understand the potential implication of uranium for the in vivo functions of the
      digestive fluids, indicating that the presence of uranium inhibits the enzyme
      activity. This inhibitory effect can be, however, suppressed by an excess of
      calcium.

PMID- 30207698
TI  - Correction to Measurement of Mobile-Phase Volume in Reversed-Phase Liquid
      Chromatography and Evaluation of the Composition of Liquid Layer Formed by
      Solvation of Packing Materials.

PMID- 30207699
TI  - Structure and Reaction Mechanism of the LigJ Hydratase: An Enzyme Critical for
      the Bacterial Degradation of Lignin in the Protocatechuate 4,5-Cleavage Pathway.
AB  - LigJ from the soil bacterium Sphingobium sp. SYK-6 catalyzes the reversible
      hydration of (3 Z)-2-keto-4-carboxy-3-hexenedioate (KCH) to 4-carboxy-4-hydroxy-2
      oxoadipate (CHA) in the degradation of lignin in the protocatechuate 4,5-cleavage
      pathway. LigJ is a member of the amidohydrolase superfamily and an enzyme in
      cog2159. The three-dimensional crystal structure of wild-type LigJ was determined
      in the presence [Protein Data Bank (PDB) entry 6DXQ ] and absence of the product
      CHA (PDB entry 6DWV ). The protein folds as a distorted (beta/alpha)8-barrel, and
      a single zinc ion is bound in the active site at the C-terminal end of the
      central beta-barrel. The product CHA is ligated to the zinc ion in the active
      site via the displacement of a single water molecule from the coordination shell
      of the metal center in LigJ. The product-bound structure reveals that the enzyme
      catalyzes the hydration of KCH with the formation of a chiral center at C4 with S
      stereochemistry. The E284Q mutant was unable to catalyze the hydration of KCH to
      CHA, and the structure of this mutant was determined in the presence of the
      substrate KCH (PDB entry 6DXS ). On the basis of the structure of LigJ in the
      presence of KCH and CHA, it is proposed that the side chain carboxylate of Glu
      284 functions as a general base in the abstraction of a proton from a bound water
      molecule for nucleophilic attack at C4 of the substrate. The reaction is
      facilitated by the delocalization of the negative charge to the metal center via
      the carbonyl group at C2 of the substrate. C3 of the substrate is subsequently
      protonated by Glu-284 functioning as a general acid. The overall reaction occurs
      by the syn addition of water to the double bond between C4 and C3 of the
      substrate KCH. The kinetic constants for the hydration of KCH to CHA by LigJ at
      pH 8.0 are 25 s-1 ( kcat) and 2.6 * 106 M-1 s-1 ( kcat/ Km).

PMID- 30207700
TI  - The Optoelectronic Nose: Colorimetric and Fluorometric Sensor Arrays.
AB  - A comprehensive review on the development and state of the art of colorimetric
      and fluorometric sensor arrays is presented. Chemical sensing aims to detect
      subtle changes in the chemical environment by transforming relevant chemical or
      physical properties of molecular or ionic species (i.e., analytes) into an
      analytically useful output. Optical arrays based on chemoresponsive colorants
      (dyes and nanoporous pigments) probe the chemical reactivity of analytes, rather
      than their physical properties (e.g., mass). The chemical specificity of the
      olfactory system does not come from specific receptors for specific analytes
      (e.g., the traditional lock-and-key model of substrate-enzyme interactions), but
      rather olfaction makes use of pattern recognition of the combined response of
      several hundred olfactory receptors. In a similar fashion, arrays of
      chemoresponsive colorants provide high-dimensional data from the color or
      fluorescence changes of the dyes in these arrays as they are exposed to analytes.
      This provides chemical sensing with high sensitivity (often down to parts per
      billion levels), impressive discrimination among very similar analytes, and
      exquisite fingerprinting of extremely similar mixtures over a wide range of
      analyte types, in both the gas and liquid phases. Design of both sensor arrays
      and instrumentation for their analysis are discussed. In addition, the various
      chemometric and statistical analyses of high-dimensional data (including
      hierarchical cluster analysis (HCA), principal component analysis (PCA), linear
      discriminant analysis (LDA), support vector machines (SVMs), and artificial
      neural networks (ANNs)) are presented and critiqued in reference to their use in
      chemical sensing. A variety of applications are also discussed, including
      personal dosimetry of toxic industrial chemical, detection of explosives or
      accelerants, quality control of foods and beverages, biosensing intracellularly,
      identification of bacteria and fungi, and detection of cancer and disease
      biomarkers.

PMID- 30207701
TI  - Characterization of Catalytic Activities and Heme Coordination Structures of Heme
      DNA Complexes Composed of Some Chemically Modified Hemes and an All Parallel
      Stranded Tetrameric G-Quadruplex DNA Formed from d(TTAGGG).
AB  - Heme binds selectively to the 3'-terminal G-quartet (G6 G-quartet) of an all
      parallel-stranded tetrameric G-quadruplex DNA, [d(TTAGGG)]4, to form a heme-DNA
      complex. Complexes between [d(TTAGGG)]4 and a series of chemically modified hemes
      possessing a heme Fe atom with a variety of electron densities were characterized
      in terms of their peroxidase activities to evaluate the effect of a change in the
      electron density of the heme Fe atom (rhoFe) on their activities. The peroxidase
      activity of a complex decreased with a decreasing rhoFe, supporting the idea that
      the activity of the complex is elicited through a reaction mechanism similar to
      that of a peroxidase. In the ferrous heme-DNA complex, carbon monoxide (CO) can
      bind to the heme Fe atom on the side of the heme opposite the G6 G-quartet, and a
      water molecule (H2O) is coordinated to the Fe atom as another axial ligand, trans
      to the CO. The stretching frequencies of Fe-bound CO (nuCO) and the Fe-C bond
      (nuFe-C) of CO adducts of the heme-DNA complexes were determined to investigate
      the structural and electronic natures of the axial ligands coordinated to the
      heme Fe atom. Comparison of the nuCO and nuFe-C values of the heme-DNA complexes
      with those of myoglobin (Mb) revealed that the donor strength of the axial
      ligation trans to the CO in a complex is considerably weaker than that of the
      proximal histidine in Mb, as expected from the coordination of H2O trans to the
      CO in the complex.

PMID- 30207702
TI  - Doubling Sensitivity in Multicollector ICPMS Using High-Efficiency, Rapid
      Response Laser Ablation Technology.
AB  - The introduction of rapid response laser ablation cells and sample transport
      technologies to laser ablation inductively coupled plasma mass spectrometry (LA
      ICPMS) has enabled signal pulse durations for a single laser ablation shot of
      less than 10 ms. These developments have resulted in marked improvements in
      analytical throughput, resolution, and sensitivity vital for the generation of
      large, highly spatially resolved elemental maps. The focus on mapping,
      particularly bioimaging, has obscured the possibility of applying the sensitivity
      advantage of rapid response technologies to other LA-ICPMS applications, such as
      high-precision isotope ratio analysis on multicollector (MC) ICPMS. In this work
      a commercially available rapid response sample transport system and a
      conventional configuration were compared for LA-MC-ICPMS analysis. Ablation of
      known reference materials demonstrated "sensitivity" or sample ion yield of 7-9%
      using the rapid response sample transport system, more than double that for the
      conventional setup. This increase in efficiency was demonstrated to improve
      precision for the Pb isotope ratio analysis of the MPI-DING reference glasses and
      improve the spatial resolution of Hf isotope ratio analysis of reference zircons.

PMID- 30207703
TI  - Fabrication of Tris(bipyridine)ruthenium(II)-Functionalized Metal-Organic
      Framework Thin Films by Electrochemically Assisted Self-Assembly Technique for
      Electrochemiluminescent Immunoassay.
AB  - A simple strategy for one-step fabrication of tris(bipyridine)ruthenium(II)
      (Ru(bpy)32+)-functionalized metal-organic framework (Ru-MOF) thin films using a
      self-assembly approach assisted by an electrochemical way was introduced. In this
      protocol, the electrochemically driven cooperative reaction of Ru(bpy)32+ as an
      electrochemiluminescent (ECL) probe and a structure-directing agent, trimesic
      acid (H3btc) as a ligand, and Zn(NO3)2 as the Zn2+ source leads to an one-step
      and simultaneous synthesis and deposition of the MOF onto the electrode surface.
      Characterization of the Ru-MOF thin films was performed with scanning electron
      microscopy, Fourier transform infrared, and X-ray photoelectron spectroscopy.
      Scanning ion conductance microscopy was specially applied in situ to image the
      topography and thickness of the Ru-MOF thin films. The Ru-MOF thin films as a
      sensing platform show excellent ECL behavior because of plenty of Ru(bpy)32+
      molecules encapsulated in the frameworks. On the basis of the Ru-MOF modified
      electrodes, an ultrasensitive label-free ECL immunosensing method for the human
      heart-type fatty-acid-binding protein has been developed with a wide linear
      response range (150 fg mL-1-150 ng mL-1) and a very low limit of detection (2.6
      fg mL-1). The prepared immunosensor also displayed excellent stability and good
      specificity in the test of practical samples.

PMID- 30207704
TI  - High-Generation Amphiphilic Janus-Dendrimers as Stabilizing Agents for Drug
      Suspensions.
AB  - Pharmaceutical nanosuspensions are formed when drug crystals are suspended in
      aqueous media in the presence of stabilizers. This technology offers a convenient
      way to enhance the dissolution of poorly water-soluble drug compounds. The
      stabilizers exert their action through electrostatic or steric interactions,
      however, the molecular requirements of stabilizing agents have not been studied
      extensively. Here, four structurally related amphiphilic Janus-dendrimers were
      synthesized and screened to determine the roles of different macromolecular
      domains on the stabilization of drug crystals. Physical interaction and
      nanomilling experiments have substantiated that Janus-dendrimers with fourth
      generation hydrophilic dendrons were superior to third generation analogues and
      Poloxamer 188 in stabilizing indomethacin suspensions. Contact angle and surface
      plasmon resonance measurements support the hypothesis that Janus-dendrimers bind
      to indomethacin surfaces via hydrophobic interactions and that the number of
      hydrophobic alkyl tails determines the adsorption kinetics of the Janus
      dendrimers. The results showed that amphiphilic Janus-dendrimers adsorb onto drug
      particles and thus can be used to provide steric stabilization against
      aggregation and recrystallization. The modular synthetic route for new
      amphiphilic Janus-dendrimers offers, thus, for the first time a versatile
      platform for stable general-use stabilizing agents of drug suspensions.

PMID- 30207705
TI  - Unveiling the Role and Mechanism of Mechanochemical Activation on Lithium Cobalt
      Oxide Powders from Spent Lithium-Ion Batteries.
AB  - This research presented the impacts of mechanochemical activation (MCA) on the
      physiochemical properties of lithium cobalt oxide (LiCoO2) powders of cathode
      materials from spent lithium-ion batteries, and analyzed the relevant effects of
      these changes on the leaching efficiency of lithium and cobalt and the leaching
      kinetics of LiCoO2 powders. The results revealed the superiority of MCA in the
      following levels of changes in the LiCoO2 powders: first, the physical properties
      included a decrease in the average particle size, an increase in the specific
      surface area, and the appearance of a mesoporous structure change; second,
      changes in crystal-phase structures were reflected in the grain refinement of
      LiCoO2 powders, lattice distortions, lattice dislocations, and storage and
      increment of internal energy; third, the surface characteristics included a
      chemical shift of lithium element electrons, a reduction in Co3+ concentration,
      and an increment in the surface hydroxyl oxygen concentration. These changes in
      physiochemical properties and structures enhanced the hydrophilicity and
      interface reactivity of the activated LiCoO2 powders and significantly improved
      the leaching efficiencies of Li and Co in organic acid solutions. The rate
      limiting step of metal leaching was also altered from a surface chemical reaction
      controlled one before MCA to an ash layer diffusion-controlled one after MCA.

PMID- 30207706
TI  - Enhancement of PM2.5 Cyclone Separation by Droplet Capture and Particle Sorting.
AB  - Fine particulate matter (PM2.5) is one of the most serious environmental
      pollutants worldwide, and efficient separation technologies are crucial to the
      control of PM2.5 emission from industrial sources. We developed a novel method to
      enhance PM2.5 cyclone separation by droplet capture and particle sorting using a
      vertical reverse rotation cyclone (VRR-C, inlet particle-sorting cyclone). The
      separation performances of common cyclone (CM-C) without droplets, CM-C with
      droplets, and VRR-C with droplets were compared in terms of energy consumption,
      overall separation efficiency, particle grade efficiency, outlet particle
      concentration, and outlet particle size distribution. The results show that the
      highest overall separation efficiencies were 51.7%, 89.9%, and 94.5% for CM-C
      without droplets, CM-C with droplets, and VRR-C with droplets, respectively, when
      the mean diameter of the inlet particles was 3.2 MUm and the inlet particle
      concentration was 500 mg/m3. The PM2.5 grade efficiency of VRR-C with droplets
      was as high as 89.8%, which was 6.2% and 49.9% higher than those of CM-C with
      droplets and CM-C without droplets, respectively. This novel method was first
      successfully applied to the deep purification of product gas in the methanol-to
      olefin (MTO) industry, for which the separation efficiency of fine catalyst
      particles was considerably improved.

PMID- 30207707
TI  - Is Sulfate Radical Really Generated from Peroxydisulfate Activated by Iron(II)
      for Environmental Decontamination?
AB  - It is well documented that the traditional Fenton reagent (i.e., the combination
      of Fe(II) and H2O2) produces hydroxyl radical (*OH) under acidic conditions,
      while at near-neutral pH the reactive intermediate converts to ferryl ion
      (Fe(IV)) that can oxidize sulfoxides to produce corresponding sulfones, markedly
      differing from their *OH-induced products. However, it remains unclear whether
      Fe(IV) is generated in the Fe(II) activated peroxydisulfate (PDS) process, where
      sulfate radical (SO4*-) is long recognized as the dominant intermediate in
      literature. Here we demonstrated that SO4*- oxidized methyl phenyl sulfoxide
      (PMSO, a model sulfoxide) to produce biphenyl compounds rather than methyl phenyl
      sulfone (PMSO2). Interestingly, the formation of PMSO2 was observed when PMSO was
      treated by the Fe(II)/PDS system over a wide pH range, and the yields of PMSO2
      were quantified to be ~100% at acidic pH 3-5. The identification of Fe(IV) in the
      Fe(II)/PDS system could also reasonably explain the literature results on alcohol
      scavenging effect and ESR spectra analysis. Further, a Fe(IV)-based kinetic model
      was shown to accurately simulate the experimental data. This work urges re
      evaluation of the Fe(II)/PDS system for environmental decontamination, given that
      Fe(IV) would have different reactivity toward environmental contaminants compared
      with SO4*- and/or *OH.

PMID- 30207708
TI  - Hydrothermal Stability of CeO2-WO3-ZrO2 Mixed Oxides for Selective Catalytic
      Reduction of NOx by NH3.
AB  - CeO2-WO3-ZrO2 mixed oxides were prepared by the homogeneous precipitation method
      for the selective catalytic reduction of NOx with NH3 (NH3-SCR). The effects of
      hydrothermal aging on the catalytic performances of CeO2-WO3-ZrO2 were
      investigated. The results showed that CeO2-WO3-ZrO2 catalyst exhibited excellent
      NH3-SCR activity for removal of NOx and hydrothermal stability. After
      hydrothermal aging at 850  degrees C for 16 h, the optimum CeO2-WO3-ZrO2 catalyst
      could still realize 80% NOx conversion at 300-500  degrees C even under a high
      gas hourly space velocity of 250 000 h-1. The structural properties, redox
      ability, surface species, and acidity of fresh and hydrothermally aged CeO2-WO3
      ZrO2 catalysts were characterized by N2-physisorption, XRD, Raman, H2-TPR, XPS,
      NH3-TPD, and in situ DRIFTS. The characterization results showed that decreases
      of 89% of the surface area and 71% of the NH3 storage capacity as well as new
      phase formation occurred for the CeO2-WO3-ZrO2 sample after hydrothermal aging at
      850  degrees C for 16 h. The activity of hydrothermally aged CeO2-WO3-ZrO2 was
      mainly attributed to the retention of redox-acid sites and their interaction due
      to the formation of Ce-Zr solid solutions and Ce4W9O33.

PMID- 30207709
TI  - Kinetics of Limonene Secondary Organic Aerosol Oxidation in the Aqueous Phase.
AB  - Twenty semivolatile organic compounds that contribute to limonene secondary
      organic aerosol (SOA) were synthesized in the flow-tube reactor. Kinetics of the
      aqueous-phase oxidation of the synthesized compounds by hydroxyl radicals (OH)
      and ozone (O3) were investigated at 298 +/- 2 K using the relative rate method.
      Oxidized organic compounds identified as the major components of limonene SOA
      were quantified with liquid chromatography coupled to the electrospray ionization
      and quadrupole tandem mass spectrometry (LC-ESI/MS/MS). The bimolecular rate
      coefficients measured for the oxidation products of limonene are kOH = 2-5 * 109
      M-1 s-1 for saturated and kOH = 1-2 * 1010 M-1 s-1 for unsaturated compounds.
      Ozonolysis reaction bimolecular rate coefficients obtained for the unsaturated
      compounds in the aqueous phase are between 2 and 6 * 104 M-1 s-1. The results
      obtained in this work also indicate that oxidation of limonene carboxylic acids
      by OH was about a factor of 2 slower for the carboxylate ions than for the
      protonated acids while the opposite was true for the ozonolysis. The data
      acquired provided new insights into kinetics of the limonene SOA processing in
      the aqueous phase. Ozonolysis of limonene SOA also increased the concentration of
      dimers, most likely due to reactions of the stabilized Criegee intermediates with
      the other, stable products. These results indicate that aqueous-phase oxidation
      of limonene SOA by OH and O3 will be relevant in clouds, fogs, and wet aerosols.

PMID- 30207710
TI  - Formation of Whey Protein Isolate (WPI)-Maltodextrin Conjugates in Fibers
      Produced by Needleless Electrospinning.
AB  - Glycation of proteins via the first stage of the Maillard reaction is capable of
      improving their stability but not economically feasible yet. This work reports
      the glycation of whey protein isolate (WPI) with maltodextrin at a high yield
      after heating electrospun fibers made from the reactants. Glycoconjugates were
      characterized by Fourier transform infrared spectroscopy (FTIR) and SDS-PAGE. The
      binding ratio between WPI and maltodextrin was assessed via the free amino
      groups. The molecular weight of the conjugates and the reaction yield were
      studied by size exclusion chromatography. The impact of different mass ratios
      between WPI and maltodextrin in the fibers (5:95, 10:90, 20:80, and 25:75 w/w)
      was investigated. With increasing WPI content, the binding ratio of maltodextrin
      decreased from ~2.1 to ~1.2. Preferably small polysaccharides (2-13 kDa) from the
      maltodextrin reacted. Protein specific reaction yields of up to 44.52 +/- 7.46%
      w/w were demonstrated in all WPI-maltodextrin fibers after heating.

PMID- 30207711
TI  - Fine-Tunable Self-Activated Luminescence in Apatite-Type (Ba,Sr)5(PO4)3Br and the
      Defect Process.
AB  - Intrinsic defect-related luminescence has recently been attracting more research
      interest for the modification of phosphors. However, the connection between
      defect formation and crystal structure has never been considered. In this work,
      we report that in the absence of an impurity activator, under a reducing
      atmosphere, apatite-type compound M5(PO4)3X (M = Ca, Sr, or Ba; X = F, Cl, or Br)
      can emit tunable colors ranging from blue to orange depending on the content of M
      and X. To better understand the cause, Ba5- mSr m(PO4)3Br (BSPOB; m = 0-5) solid
      solutions were analyzed in detail. The dependency of self-activated luminescence
      on atmospheric conditions and solid solution compositions was investigated by
      combining experimental characterizations and theoretical calculations using
      density functional theory. Crystal structures of these solid solutions were
      verified by X-ray diffraction patterns as well as Rietveld refinements. With the
      defect formation energy and electron paramagnetic resonance measurement, we
      propose that an oxygen vacancy (VO) should be mainly responsible for the peculiar
      super wide band emission. Moreover, the enhanced distortion of solid solution
      crystal structures augments VO concentrations and leads to luminescence
      intensities in solid solutions that are higher than that in end point compounds.
      Variations of the electronic structure of BSPOB matrices with gradual tuning of
      the Sr/Ba ratio were also investigated. As a result, the introduction of VO
      defect levels within the band gap leads to the formation of donors and acceptors,
      allowing for a modulation of the photoluminescence throughout the visible part of
      the spectrum. As the first report in the literature to demonstrate fine-tunable
      emissions over a wide wavelength range as a consequence of native defective
      levels in a series of continuous apatite-type solid solutions, our results
      illustrate the feasibility of defect-meditated systems by carefully tailoring
      defect chemistry and nonstoichiometric chemical composition under controlled
      conditions to engineer phosphor properties.

PMID- 30207712
TI  - Switching Harmful Algal Blooms to Submerged Macrophytes in Shallow Waters Using
      Geo-engineering Methods: Evidence from a 15N Tracing Study.
AB  - Switching the dominance from algae to macrophytes is crucial for lake management
      of human-induced eutrophication. Nutrients from algal sources can be utilized in
      the process of transition from algal blooms to macrophytes, thereby mitigating
      eutrophication. However, this process rarely occurs in algal bloom dominated
      waters. Here, we examined the hypothesis that the transition of algal blooms to
      macrophytes and the transfer of nutrients from algae at different temperatures (8
      and 25  degrees C) can be facilitated by using a geo-engineering method. The
      results showed that the combination of flocculation and capping treatment could
      not only remove Microcystis aeruginosa blooms from eutrophic waters but also
      facilitate algal decomposition and incorporation into a submerged macrophyte (
      Potamogeton crispus) biomass. The flocculation-capping treatment could trigger
      algal cell lysis. As compared with the control groups, the photosynthesis and
      respiration rate of algae were inhibited and chlorophyll-a (Chl- a)
      concentrations were significantly reduced in the flocculation-capping treatment
      groups. The 15N tracing study revealed that 3.3% and 34.8% of algae-derived
      nitrogen could be assimilated by Potamogeton crispus at 8 and 25  degrees C,
      respectively. The study demonstrated that the flocculation-capping method can
      facilitate the switchover from algae- to the macrophyte-dominated state, which is
      crucial for restoring the aquatic ecosystem.

PMID- 30207713
TI  - Unveiling the Intercalation Mechanism in Fe2(MoO4)3 as an Electrode Material for
      Na-Ion Batteries by Structural Determination.
AB  - Monoclinic Fe2(MoO4)3 (FMO) shows distinct structural and electrochemical
      differences in the intercalation mechanism, depending on the guest ion. (1,2) FMO
      undergoes a single-phase reaction in a Na-ion cell, but a two-phase reaction in a
      Li-ion cell. Attempts to understand the difference in the mechanisms have been
      hindered by a lack of structural information on the fully sodiated phase
      Na2Fe2(MoO4)3 due to its structural complexity and the unavailability of a single
      crystal. In this work, we have solved and refined the crystal structure of
      Na2Fe2(MoO4)3 for the first time, using the technique of ab initio structure
      determination from powder diffraction data. Along with electrochemical and
      structural characterization, 3D bond valence sum difference map calculations
      enabled us to ascertain the decisive factors that determine such differences, in
      terms of the interatomic distance and coordination environment of a guest ion. In
      the case of Na insertion, only a slight expansion of the structure makes the
      cavity sites of FMO suitable for Na ions, with adequate distances and
      coordination with surrounding oxygen atoms, resulting in a solid-solution-type
      single-phase reaction. In the case of Li insertion, the cavity sites are so large
      for a Li ion that a significant structural change involving tilting of the FeO6
      and MoO4 polyhedra is required to accommodate the Li ion in a suitable local
      environment, which does not allow a continuous structural change but results in a
      two-phase reaction.

PMID- 30207714
TI  - Bioavailability of Quercetin from Onion Extracts after Intraruminal Application
      in Cows.
AB  - The aim of the present study was to investigate the bioavailability of quercetin
      from onion bulb (OB) and onion skin (OS) extracts in ruminants. Three non
      lactating cows equipped with a permanent rumen fistula intraruminally received
      equimolar amounts of quercetin as either aglycone, rutin, or OB or OS extract,
      respectively, at a dose of 50 mg of quercetin equivalents/kg of body weight.
      Blood samples were drawn before and frequently within the 24 h period after
      application of the respective substance. Quercetin and quercetin metabolites with
      an intact flavonol structure (kaempferol, isorhamnetin, and tamarixetin) were
      analyzed in plasma samples by high-performance liquid chromatography with
      fluorescence detection. All quercetin sources administered resulted in a fast
      increase of the plasma concentrations of quercetin and total flavonols (sum of
      quercetin and its metabolites), followed by a rapid decline, whereby significant
      higher concentrations occurred with OB extract and rutin compared to quercetin
      aglycone and OS extract, respectively. The results clearly demonstrate a higher
      systemic availability of quercetin from OB extract and rutin. Taken together, OB
      extract with a high content of quercetin glucosides is an interesting source for
      the application of quercetin to ruminants.

PMID- 30207716
TI  - Nighttime Light Images Reveal Spatial-Temporal Dynamics of Global Anthropogenic
      Resources Accumulation above Ground.
AB  - Urbanization and industrialization represent largely a process of transforming
      materials from biosphere and lithosphere to anthroposphere. Understanding the
      patterns of such anthropogenic material stock accumulation is thus a fundamental
      prerequisite to assess and sustain how humans alter the biophysical movements of
      resources around Earth. Previous studies on these anthropogenic stocks, however,
      are often limited to the global and national scales, due to data gaps at higher
      spatial resolutions. Here, based on a new set of national materials stock data
      and nighttime light images, we developed a regression model to map the global
      anthropogenic stocks of three fundamental construction materials (steel,
      concrete, and aluminum) at a 1 * 1 km level from 1992 to 2008. We revealed an
      unevenly distributed pattern, with over 40% found in three belts: from England
      across the Channel to Western Europe; from eastern coast China to South Korea and
      Japan; and from Great Lakes along eastern coast of United States to Florida. The
      spatial-temporal dynamics of global anthropogenic stocks at smaller spatial
      scales reflect a combined effect of physical geography, architectural and
      construction specifications, and socioeconomic development. Our results provide
      useful data that can potentially support policy-makers and industry on resource
      efficiency, waste management, urban mining, spatial planning, and environmental
      sustainability at regional and urban scales.

PMID- 30207715
TI  - Switchable Spin-Crossover Hofmann-Type 3D Coordination Polymers Based on Tri- and
      Tetratopic Ligands.
AB  - FeII spin-crossover (SCO) coordination polymers of the Hofmann type have become
      an archetypal class of responsive materials. Almost invariably, the construction
      of their architectures has been based on the use of monotopic and linear ditopic
      pyridine-like ligands. In the search for new Hofmann-type architectures with SCO
      properties, here we analyze the possibilities of bridging ligands with higher
      connectivity degree. More precisely, the synthesis and structure of
      {FeII(LN3)[MI(CN)2]2}.(Guest) (Guest = nitrobenzene, benzonitrile, o
      dichlorobenzene; MI = Ag, Au) and {FeII(LN4)[Ag2(CN)3][Ag(CN)2]}.H2O are
      described, where LN3 and LN4 are the tritopic and tetratopic ligands 1,3,5
      tris(pyridin-4-ylethynyl)benzene and 1,2,4,5-tetrakis(pyridin-4
      ylethynyl)benzene. This new series of Hofmann clathrates displays thermo- and
      photoinduced SCO behaviors.

PMID- 30207717
TI  - Evaluation of Variability in Greenhouse Gas Intensity of Canadian Oil Sands
      Surface Mining and Upgrading Operations.
AB  - We present a statistically enhanced version of the GreenHouse gas emissions of
      current Oil Sands Technologies model that facilitates characterization of
      variability of greenhouse gas (GHG) emissions associated with mining and
      upgrading of bitumen from Canadian oil sands. Over 30 years of publicly available
      project-specific operating data are employed as inputs, enabling Monte Carlo
      simulation of individual projects and the entire industry, for individual years
      and project life cycles. We estimate that median lifetime GHG intensities range
      from 89 to 137 kg CO2eq/bbl synthetic crude oil (SCO) for projects that employ
      upgrading. The only project producing dilbit that goes directly to a refinery has
      a median lifetime GHG intensity of 51 kg CO2eq/bbl dilbit. As SCO and dilbit are
      distinct products with different downstream processing energy requirements, a
      life cycle assessment ("well to wheel") is needed to properly compare them.
      Projects do not reach steady-state in terms of median GHG intensity. Projects
      with broader distributions of annual GHG intensities and higher median values are
      linked to specific events (e.g., project expansions). An implication for
      policymakers is that no specific technology or operating factor can be directly
      linked to GHG intensity and no particular project or year of operation can be
      seen as representative of the industry or production technology.

PMID- 30207718
TI  - Polymer Identification of Plastic Debris Ingested by Pelagic-Phase Sea Turtles in
      the Central Pacific.
AB  - Pelagic Pacific sea turtles eat relatively large quantities of plastic (median 5
      g in gut). Using Fourier transform infrared spectroscopy, we identified the
      polymers ingested by 37 olive ridley, 9 green, and 4 loggerhead turtles caught as
      bycatch in Hawaii- and American Samoa-based longline fisheries. Unidentifiable
      samples were analyzed using high-temperature size exclusion chromatography with
      multiple detectors and/or X-ray photoelectron spectroscopy. Regardless of species
      differences in dive depths and foraging strategies, ingested plastics were
      primarily low-density, floating polymers (51% low-density polyethylene (LDPE),
      26% polypropylene (PP), 10% unknown polyethylene (PE), and 5% high-density PE
      collectively). Albeit not statistically significant, deeper diving and deeper
      captured olive ridley turtles ate proportionally more plastics expected to sink
      (3.9%) than intermediate-diving green (1.2%) and shallow-diving loggerhead (0.3%)
      turtles. Spatial, but no sex, size, year, or hook depth differences were observed
      in polymer composition. LDPE and PP, some of the most produced and least recycled
      polymers worldwide, account for the largest percentage of plastic eaten by sea
      turtles in this region. These novel data inform managers about the threat of
      plastic ingestion to sea turtles and may motivate development of more
      environmentally friendly practices for plastic production, use, and waste
      management.

PMID- 30207719
TI  - Effect of Ribose Conformation on RNA Cleavage via Internal Transesterification.
AB  - RNA cleavage via internal transesterification is a fundamental reaction involved
      in RNA processing and metabolism, and the regulation thereof. Herein, the
      influence of ribose conformation on this reaction was investigated with
      conformationally constrained ribonucleotides. RNA cleavage rates were found to
      decrease in the order South-constrained ribonucleotide > native ribonucleotide ?
      North-constrained counterpart, indicating that the ribose conformation plays an
      important role in modulating RNA cleavage via internal transesterification.

PMID- 30207720
TI  - Dihydrochalcone Glucosides from the Subaerial Parts of Thonningia sanguinea and
      Their in Vitro PTP1B Inhibitory Activities.
AB  - Six new and four known dihydrochalcone glucoside derivatives (1-10), the
      phenylpropanoid coniferin (11), and the lignans (+)-pinoresinol (12) and
      lariciresinol (13) were isolated from the subaerial plant parts of Thonningia
      sanguinea in the course of a screening campaign for new antidiabetic lead
      compounds. The structures of the new substances were elucidated by HRESIMS, NMR,
      GC-MS, and ECD data evaluation. 2'- O-(3-Galloyl-4,6- O- Sa-hexahydroxydiphenoyl
      beta-d-glucopyranosyl)-3-hydroxyphloretin (4), 2'- O-(4,6- O- Sa
      hexahydroxydiphenoyl-beta-d-glucopyranosyl)phloretin (5), 2'- O-(3- O-galloyl-4,6
      O- Sa-hexahydroxydiphenoyl-beta-d-glucopyranosyl)phloretin (6), and
      thonningianin B (9) showed moderate protein tyrosine phosphatase-1B inhibition in
      an enzyme assay (IC50 values ranging from 19 to 25 MUM), whereas thonningianin A
      (10) was identified as a more potent inhibitor (IC50 = 4.4 MUM). The observed
      activity differences could be explained by molecular docking experiments. The
      activity of 10 could further be confirmed in HEPG2 liver carcinoma cells, where
      the compound was able to increase the level of phosphorylated insulin receptors
      in a concentration-dependent manner.

PMID- 30207721
TI  - A Molecular Hybridization Approach for the Design of Potent, Highly Selective,
      and Brain-Penetrant N-Myristoyltransferase Inhibitors.
AB  - Crystallography has guided the hybridization of two series of Trypanosoma brucei
      N-myristoyltransferase (NMT) inhibitors, leading to a novel highly selective
      series. The effect of combining the selectivity enhancing elements from two
      pharmacophores is shown to be additive and has led to compounds that have greater
      than 1000-fold selectivity for TbNMT vs HsNMT. Further optimization of the hybrid
      series has identified compounds with significant trypanocidal activity capable of
      crossing the blood-brain barrier. By using CF-1 mdr1a deficient mice, we were
      able to demonstrate full cures in vivo in a mouse model of stage 2 African
      sleeping sickness. This and previous work provides very strong validation for NMT
      as a drug target for human African trypanosomiasis in both the peripheral and
      central nervous system stages of disease.

PMID- 30207722
TI  - Aturanosides A and B, Glycosylated Anthraquinones with Antiangiogenic Activity
      from a Soil-Derived Streptomyces Species.
AB  - A chemical investigation of a culture extract from a soil-derived Streptomyces
      sp. RK88-1441 led to the isolation and characterization of two new glycosylated
      anthraquinones, aturanosides A (1) and B (2), and a new anthraquinone derivative,
      aturanocin (3). The structures of these compounds were elucidated by detailed NMR
      and MS spectroscopic analyses. The absolute configurations of the sugar units,
      based on the magnitudes of the coupling constants, ROESY correlations, and
      chemical derivatization, from 1 and 2 are 6- O-[ N-acetyl-alpha-d-glucosamino-(1
      >2)-alpha-l-rhamnoside] and 6- O-alpha-l-rhamnoside, respectively. Compounds 1
      and 2 showed no cytotoxicity against human umbilical vein endothelial cells
      (HUVECs), but significantly suppressed vascular endothelial growth factor (VEGF)
      induced tube formation and invasion of HUVECs. The down-regulation of both the
      phosphorylation of VEGF receptor 2 and the expression of vascular endothelial
      cadherin at the protein level were also observed.

PMID- 30207724
TI  - Decomposition of Moller-Plesset Energies within the Quantum Theory of Atoms-in
      Molecules.
AB  - We discuss two main approaches to decompose the Moller-Plesset perturbation
      theory molecular energies into atomic contributions within the interacting
      quantum atoms (IQA) formalism, as implemented in the programs Morphy and AIMAll.
      For this purpose, the so-called intraatomic energies (also known as self
      energies) of a representative set of 55 small molecules are compared with each
      other. The origin of the possible discrepancies between both approaches is
      analyzed, and linear models linking the two approaches are proposed for each atom
      type.

PMID- 30207723
TI  - Determination of Five Sex Hormones in Urine Samples for Early Evaluation of Male
      Reproductive Toxicity Induced by Phthalate Esters in Rats.
AB  - In this work, male rats were exposed to multiple phthalate esters (MIXPs) in a
      long-term low-dose model for the early evaluation of reproductive toxicity. An
      ananlysis method with better sensitivity, accuracy and precision was established
      to determine the five sex hormones (androstenedione, testosterone,
      dehydroepiandrosterone, dihydrotestosterone, and estrone) in collected urine
      samples. The results showed that all the analytes in the MIXPs treated group
      changed in a time-dependent manner. Specifically, estrone significantly decreased
      from the 30th day and the other four changed from the 30th day and then
      significantly increased on the 60th day, while no obvious changes were found in
      the control group. Therefore, a possible way was provided for the early
      evaluation of male reproductive toxicity induced by Phthalate esters (PEs) . The
      reliability of judgment was improved by observing the changes of five target
      hormones simultaneously. Furthermore, good compliance was predicted for the
      practical application due to the noninvasive and convenient urine sample
      collection.

PMID- 30207725
TI  - Thermally Induced S-Sublattice Transition of Li3PS4 for Fast Lithium-Ion
      Conduction.
AB  - The ion-transport phenomenon, determined by the interaction of strain and
      electrostatic energy, is one of the most important examples that confirms the
      effects of the polymorphism and atomic morphology. We investigated the
      correlation between the structural morphology and Li-ion conduction
      characteristics in alpha-Li3PS4, a high-temperature phase of the Li3PS4, using ab
      initio molecular dynamics (AIMD) calculations. We successfully reproduced the
      thermal disorder and partial occupancy observed at high temperatures by AIMD and
      confirmed the Li-ion sites and its migration pathways. The activation energy and
      Li-ion conductivity of alpha-Li3PS4 at room temperature were predicted to be
      about 0.18 eV and 80 mS cm-1, respectively, indicating that alpha-Li3PS4 is one
      of the fastest Li-ion conductors known so far. The fast Li-ion conduction in
      alpha-Li3PS4 is mainly caused by the BCC S-sublattice and tetrahedron-tetrahedron
      pathway with fully occupied Li-ion sites. Therefore, alpha-Li3PS4 having a BCC S
      sublattice offers a promising structural morphology for effective Li-ion
      conduction.

PMID- 30207726
TI  - Thermal Decomposition Mechanism of Aqueous Hydroxylammonium Nitrate (HAN):
      Molecular Simulation and Kinetic Modeling.
AB  - A detailed mechanism has been developed for thermal decomposition of
      hydroxylammonium nitrate (HAN) solutions, based on quantum mechanical
      calculations using the SMD-omegaB97X-D method. The mechanism describes multiple
      kinetic processes, including nitration and nitrosation of hydroxylamine, HNO
      dimerization, and HONO-regeneration pathways involving H-abstraction reactions.
      Rate constants of elementary reactions were estimated using transition state
      theory with consideration of species' diffusion effect. Kinetic modeling was
      performed to predict species' evolutions in 0.1 m HAN in the temperature range of
      463-523 K, and results show reasonable agreement with the experimental data from
      flow reactor studies. For more concentrated solutions, strong autocatalytic
      behaviors were predicted with the late emergence of NO2 and HONO, whose
      regeneration was previously considered as the major autocatalytic pathway.
      Sensitivity analysis results suggest an acid-catalyzed nitration-nitrosation
      pathway, based on which the autocatalysis should be caused by the rise of
      solution acidity. A linear correlation can be observed in the previously reported
      apparent Arrhenius parameters, which may be reconciled via a kinetic compensation
      effect.

PMID- 30207727
TI  - Asymmetric Synthesis of Chiral Spiroketal Bisphosphine Ligands and Their
      Application in Enantioselective Olefin Hydrogenation.
AB  - A series of chiral spiroketal bisphosphine ligands containing 1,1'-spirobi(3 H,3'
      H)isobenzofuran backbones was accessed through asymmetric synthesis and
      subsequently tested in enantioselective Rh-catalyzed hydrogenation of alpha
      dehydroamino acid esters. The ligand providing the highest enantioselectivity (up
      to 99.5%) was obtained in seven steps in an overall 38% yield. The synthesis
      could be performed on a gram scale, and no kinetic resolution of enantiomers is
      required. Overall, the developed ligand provides an easily accessible alternative
      to SDP ligands as well as other chiral bisphosphine ligands.

PMID- 30207728
TI  - Photodriven Deprotonation of Alcohols by a Quinoline Photobase.
AB  - Control of proton transfer is relevant to many areas in chemistry, particularly
      in catalysis where the kinetics of (de)protonation reactions are often rate
      limiting. Photobases, which are molecules with enhanced basicity in the excited
      state, allow for control of proton transfer with light and have the potential to
      be used as functional units in catalytic systems. Alcohols are the feedstock in
      many catalytic reactions, where their deprotonation or dehydrogenation is often
      important. We report that the photobase 5-methoxyquinoline can deprotonate a
      series of alcohols upon excitation by light. We measure both the thermodynamic
      limits and the relevant kinetics of this process. A series of alcohols and water
      spanning the p Ka range of 12.5-16.5 were used as the proton donors. First, we
      show evidence from absorption and emission spectroscopy that photoexcited 5
      methoxyquinoline deprotonates all donors more acidic than methanol and fails to
      deprotonate donors that are more basic. Interestingly, in methanol a quasi
      equilibrium between the protonated and unprotonated forms of the photobase is
      established in the excited state, suggesting that the excited state p Ka of the
      photobase is near the p Ka of methanol (15.5). Second, using ultrafast transient
      absorption spectroscopy, we find that the time constants for excited state proton
      transfer range from a few picoseconds to tens of picoseconds, with faster speeds
      for the more acidic donors. Such a correlation between the thermodynamic drive
      and kinetics suggests that the same mechanism is responsible for proton transfer
      throughout the series. These results are necessary fundamental steps for applying
      photobases in potential applications such as deprotonation of alcohols for
      catalytic and synthetic purposes, optical regulation of pH, and transfer of
      protons in redox reactions.

PMID- 30207729
TI  - Pressure-Induced Variations of Aggregation Structures in Colorless and
      Transparent Polyimide Films Analyzed by Optical Microscopy, UV-Vis Absorption,
      and Fluorescence Spectroscopy.
AB  - Pressure-induced variations in the main chain and aggregation structures of
      colorless and transparent semialiphatic polyimide (PI) films were investigated by
      optical microscopy, UV-vis absorption, and fluorescence spectroscopy up to 8 GPa.
      Upon application of pressures up to 2 GPa, a gradual volumetric compression was
      clearly observed by microscopy, and definite bathochromic shifts of locally
      excited (LE) absorption bands were detected, which was attributed to the
      compression of interchain free volume and enhanced intermolecular interactions.
      In addition, a significant reduction in fluorescence intensity was observed for
      PIs with quasilinear structures below 2 GPa due to enhanced energy transfer in
      the excited states caused by the densification of PI chain packing. In contrast,
      the volumetric compression of the PI films and bathochromic shifts of the LE
      absorption bands were gradually reduced at pressures above 2 GPa. The former is
      closely correlated with the bulkiness and flexibility of the alicyclic diamine
      structure. The latter reflects the intense compression stress generated around
      the dianhydride moiety, associated with the deformability and in-plane
      orientation of the main PI chains. High-pressure experiments on PI films are
      beneficial to investigate variations in aggregation structures and local
      electronic structures of PI chains induced by dense molecular packing and
      enhanced intermolecular interactions.

PMID- 30207730
TI  - Electronically Mismatched Cycloaddition Reactions via First-Row Transition Metal,
      Iron(III)-Polypyridyl Complex.
AB  - The iron(III)-polypyridyl complex and its derivatives showed sufficient oxidizing
      potential to act as a one-electron oxidant, producing radical cations from
      olefins and promoting the efficient radical cation [2 + 2] and [2 + 4]
      cycloaddition reactions. Subsequent chain propagation afforded trisubstituted
      cyclobutane or cyclohexene derivatives, and this facile route enables the
      replacement of rare metals with sustainable, green, and inexpensive iron in
      radical cation cycloadditions.

PMID- 30207731
TI  - Total Synthesis of Chaetoglobin A via Catalytic, Atroposelective Oxidative Phenol
      Coupling.
AB  - The first total synthesis of chaetoglobin A (1), which features a chiral axis
      between two identical highly oxygenated bicyclic cores, was successfully
      completed in 12 steps from 2,6-dimethoxytoluene. Vanadium-catalyzed oxidative
      phenol coupling, as a key step, enabled generation of the axial chirality.

PMID- 30207732
TI  - Synergetic and Antagonistic Molecular Effects Mediated by the Feedback Loop of
      p53 and JNK between Saikosaponin D and SP600125 on Lung Cancer A549 Cells.
AB  - We jointly analyzed the changes in cell cycle arrest and distribution, the
      accumulation of subphase cells, apoptosis, and proliferation in A549 cells
      treated with Saikosaponin D (Ssd) and JNK inhibitor SP600125 alone or in
      combination. Our results indicated that cell cycle arrest at G0/G1, S, and G2/M
      phases was coupled with the accumulation of subG1, subS, and subG2 cells,
      corresponding to early apoptosis, DNA endoreplication, and later inhibitory
      proliferation, respectively. Analyzing the expression of 18 cell cycle regulatory
      genes and JNK and phosphorylated JNK (pJNK) levels revealed an enhancement in
      these factors by Ssd. Additional SP600125 weakened or eliminated the Ssd-induced
      increase of these factors except that p53/p21 and Rassfia levels were further
      improved. Ingenuity Pathway Analysis (IPA) of the interactions of these factors
      revealed a negative synergistic effect on apoptosis while a positive synergistic
      effect on proliferative inhibition of the two drugs: (1) Ssd induced apoptosis
      via the activation of two axes, TGFalpha-JNK-p53 and TGFalpha-Rassfia-Mst1. By
      eliminating the Ssd-induced increase of JNK/pJNK, additional SP600125 weakened
      the Ssd-induced apoptotic axis of TGFalpha-JNK-p53 and simultaneously abolished
      Ssd-induced apoptosis; (2) Ssd inhibited proliferation by the activation of two
      axes, TGFbeta-p53/p21/p27/p15/p16 and TGFalpha-Rassfia-cyclin D1. By improving
      the Ssd-induced increase of p53/p21 and Rassfia, additional SP600125 enhanced the
      two axes of Ssd-induced inhibitory proliferation. Analyzing JNK/pJNK, p53,
      phospho-p53, and TNF-alpha levels revealed an opposite association of JNK/pJNK
      with p53 while consistent with phospho-p53 and TNF-alpha, which supported the
      proposals that JNK/pJNK negatively regulated p53 level, while it mediated p53
      phosphorylation to transcriptionally activate TNF-alpha expression of apoptotic
      gene and trigger apoptosis. With the multiple roles, JNK/pJNK forms a synergetic
      and antagonistic feedback loop with phospho-p53/p53. Within the feedback loop,
      (1) Ssd-induced apoptosis depended on JNK/pJNK activities mediating phospho-p53
      that activated TNF-alpha expression; (2) by weakening the negative regulation of
      JNK/pJNK in p53, SP600125 enhanced p53 level and the Ssd-induced inhibitory
      proliferation axes of TGFbeta-p53/p21/p27/p15/p16. The results indicated the
      central coordinating roles of the feedback loop in the synergistic and
      antagonistic effects of the two drugs in A549 cells and provided a rationale for
      the combination of Ssd with SP600125 in the treatment of lung cancer.

PMID- 30207733
TI  - One-Dimensional Atomic Segregation at Semiconductor-Metal Interfaces of
      Polymorphic Transition Metal Dichalcogenide Monolayers.
AB  - Interface segregation is a powerful approach to tailor properties of bulk
      materials by interface engineering. Nevertheless, little is known about the
      chemical inhomogeneity at interfaces of polymorphic two-dimensional transition
      metal dichalcogenides (TMDs) and its influence on the properties of the 2D
      materials. Here we report one-dimensional monatomic segregation at coherent
      semiconductor-metal 1H/1T interfaces of Mo-doped WS2 monolayers. The monatomic
      interface segregation takes place at an intact transition metal plane and is
      associated with the topological defects caused by reflection symmetry breaking at
      the 1T/1H interfaces and the weak difference in bonding strength between Mo-S and
      W-S. This finding enriches our understanding of the interaction between
      topological defects and impurities in 2D crystals and enlightens a potential
      approach to manipulate the properties of 2D TMDs by local chemical modification
      and interface engineering for applications in 2D TMD electronic devices.

PMID- 30207734
TI  - Toward the Design of Molecular Chameleons: Flexible Shielding of an Amide Bond
      Enhances Macrocycle Cell Permeability.
AB  - A series of macrocycles inspired by natural products were synthesized to
      investigate how side-chains may shield amide bonds and influence cell
      permeability. NMR spectroscopy and X-ray crystallography revealed that the phenyl
      group of phenylalanine, but not the side-chains of homologous or aliphatic amino
      acids, shields the adjacent amide bond through an intramolecular NH-pi
      interaction. This resulted in increased cell permeability, suggesting that NH-pi
      interactions may be used in the design of molecular chameleons.

PMID- 30207735
TI  - Generative Model for the Inverse Design of Metasurfaces.
AB  - The advent of metasurfaces in recent years has ushered in a revolutionary means
      to manipulate the behavior of light on the nanoscale. The design of such
      structures, to date, has relied on the expertise of an optical scientist to guide
      a progression of electromagnetic simulations that iteratively solve Maxwell's
      equations until a locally optimized solution can be attained. In this work, we
      identify a solution to circumvent this conventional design procedure by means of
      a deep learning architecture. When fed an input set of customer-defined optical
      spectra, the constructed generative network generates candidate patterns that
      match the on-demand spectra with high fidelity. This approach reveals an
      opportunity to expedite the discovery and design of metasurfaces for tailored
      optical responses in a systematic, inverse-design manner.

PMID- 30207736
TI  - Large Carrier Mobilities in ErMnO3 Conducting Domain Walls Revealed by
      Quantitative Hall-Effect Measurements.
AB  - Kelvin probe force microscopy (KPFM) has been used to directly and quantitatively
      measure Hall voltages, developed at conducting tail-to-tail domain walls in
      ErMnO3 single crystals, when current is driven in the presence of an
      approximately perpendicular magnetic field. Measurements across a number of
      walls, taken using two different atomic force microscope platforms, consistently
      suggest that the active p-type carriers have unusually large room temperature
      mobilities of the order of hundreds of square centimeters per volt second.
      Associated carrier densities were estimated to be of the order of 1013 cm-3. Such
      mobilities, at room temperature, are high in comparison with both bulk oxide
      conductors and LaAlO3-SrTiO3 sheet conductors. High carrier mobilities are
      encouraging for the future of domain-wall nanoelectronics and, significantly,
      also suggest the feasibility of meaningful investigations into dimensional
      confinement effects in these novel domain-wall systems.

PMID- 30207737
TI  - Paramedic and physician perspectives on the potential use of remotely supported
      prehospital ultrasound.
AB  - INTRODUCTION: During remotely supported prehospital ultrasound (RSPU), an
      ultrasound operator performs a scan and sends images to a remote expert for
      interpretation. This novel technology has been undergoing investigation in the
      randomised controlled SatCare trial, which seeks to assess the capability of RSPU
      to improve patient outcomes and standard of prehospital care in the Highlands of
      Scotland. This study aimed to explore the views of emergency medicine physicians
      and paramedics prior to starting the trial. METHODS: An interview schedule was
      prepared a priori and was based upon normalisation process theory (NPT), which
      can be used to assess ways in which practitioners work to embed novel
      technologies in clinical practice. Semi-structured interviews were conducted with
      four consultant physicians and eight paramedics, who were recruited using
      purposive sampling until theoretical saturation. Analysis used open and
      hierarchical axial coding, and NPT as a framework to assist in the management and
      analysis of codes. RESULTS: The prospect of RSPU evoked significantly different
      responses from emergency care physicians and paramedics. Paramedics thought of
      RSPU as a logical progression of prehospital care, which addresses core
      prehospital challenges such as lack of decision-making support and a limited
      ability to identify life-threatening occult conditions. Paramedics saw RSPU as
      part of a trend to increase their skills and responsibilities, and viewed
      ultrasound as a validated tool within emergency medicine. Paramedics felt that
      ultrasound was simple to learn and would be practical for use within the
      prehospital arena. In contrast, physicians expressed a greater spectrum of views;
      most saw limited value to prehospital diagnosis and were concerned that RSPU
      would distract both paramedics and physicians from their existing roles
      (particularly in the context of the increasing demand and workload within
      Scotland's publicly funded National Health Service). Physicians were also
      concerned that ultrasound skills were poorly incorporated into training and
      practice in the British emergency medicine system. Furthermore, they believed
      that ultrasound was difficult to learn, prone to misinterpretation and easy to
      become deskilled in. Both sets of participants believed that the relational
      skills required between the two groups and the practical complexities of RSPU may
      pose challenges in its implementation. In particular, concerns were raised
      regarding the time that would be required to conduct the ultrasound scans and
      difficulties with transmission and communication in the Highlands. Both groups
      questioned the likelihood of measurable benefits from RSPU for patients.
      Furthermore, both groups were unsure how the technology would benefit those
      patients in urban areas close to the emergency department or whether RSPU would
      be effectively utilised in rural areas where serious emergencies are infrequent.
      CONCLUSION: There are substantial differences in emergency physician and
      paramedic perspectives on RSPU; however, both parties were willing to engage with
      the research process. Both groups have reservations, especially the emergency
      physicians who perceive significant barriers to the acquisition of skills, as
      well as the relational and contextual integration of RSPU. This study
      demonstrates the importance of conversations with physicians and paramedics
      throughout the research process, particularly as the role of prehospital care
      remains controversial.

PMID- 30207738
TI  - Endobronchial Ultrasound Elastography Helps Identify Fibrotic Lymph Nodes in
      Sarcoidosis.

PMID- 30207740
TI  - Naturopathic Approaches to Irritable Bowel Syndrome-A Delphi Study.
AB  - INTRODUCTION: Irritable bowel syndrome (IBS) affects 11% of the population, and
      up to 50% of patients report using complementary and alternative medicines (CAM)
      for it. To date, there is no research describing how providers of naturopathic
      medicine in North America, a well-defined CAM profession, approach IBS. METHODS:
      A Delphi study was conducted over a 17-month period in 4 rounds with 15 North
      American naturopathic medicine experts in IBS. Consensus was defined as a median
      value of 75% or greater agreement with the relevant statement. RESULTS: Consensus
      was met with 45 statements describing a "reasonable naturopathic approach" to
      IBS. These statements covered the domains of general, office visits, tracking
      progress, testing, interventions, and resources. CONCLUSION: These results
      represent the beginning of an evidence base depicting naturopathic interventions
      for IBS and should inform future randomized controlled clinical trials in this
      area. Future research should look to reflect on and revise these guidance
      consensus statements particularly extending to other stakeholders as well as
      geographic and regulatory jurisdictions in the naturopathic profession.

PMID- 30207739
TI  - Field and laboratory findings following the large-scale use of intermediate type
      infectious bursal disease vaccines in Denmark.
AB  - Following a period of clinical outbreaks of very virulent infectious bursal
      disease virus (vvIBDV) in Denmark, the histological bursal lesion score (HBLS)
      was used on a national scale to screen broiler flocks vaccinated with
      intermediate IBD vaccines for lesions indicative of IBDV challenge. High lesion
      scores were detected in a high percentage of healthy and well performing flocks
      despite the lack of other indications of the presence of vvIBDV. RT-PCR and
      subsequent sequencing showed the frequent presence of H253Q and H253N IBDV
      strains that were genetically close to the sequence of the intermediate vaccines
      with a relative risk ratio of 13.0 (P < 0.0001) in intermediate vaccine A or B
      vaccinated flocks compared to unvaccinated flocks. The relevance of these H253Q
      and H253N strains was tested under experimental conditions using a protocol
      derived from the European Pharmacopoeia for safety of live IBD vaccines. The
      results confirmed the higher pathogenicity for the bursa of these strains
      compared to intermediate vaccines as well as the negative effect on antibody
      response to a Newcastle disease (ND) vaccination performed at the peak of the
      bursa damage. The efficacy of the ND vaccination was still 100% showing that the
      H253N and H253Q IBDV strains would be considered as safe vaccine viruses. In
      conclusion, the use of the HBLS to screen commercial broiler flocks vaccinated
      with intermediate IBD vaccines for the presence of vvIBDV does not seem to be a
      reliable method due to the frequent occurrence of H253N and H253Q strains in
      those flocks. For screening of IBD vaccinated flocks for the presence of vvIBDV
      or other field strains, the RT-PCR with subsequent sequencing seems to be most
      suitable.

PMID- 30207741
TI  - Clinical and Radiological Long-term Results After Implant-Free, Autologous, Iliac
      Crest Bone Graft Procedure for the Treatment of Anterior Shoulder Instability.
AB  - BACKGROUND: The implant-free, autologous, iliac crest bone graft procedure (J
      bone graft) for the treatment of anterior shoulder instability shows low rates of
      recurrent dislocations and moderate progression of instability arthropathy in the
      midterm follow-up. PURPOSE: To analyze the clinical and radiological long-term
      results of the J-bone graft procedure. STUDY DESIGN: Case series; Level of
      evidence, 4. METHODS: A total of 46 patients (47 shoulders) with anterior
      shoulder instability and a relevant bony glenoid defect who received a J-bone
      graft between 1993 and 2000 and who were previously subjected to a midterm follow
      up (mean, 8 years) were included. In total, 34 patients and 35 shoulders (74%)
      were clinically and radiologically assessed after a mean follow-up of 18 years
      (range, 15-23 years). Patients were assessed in terms of pain, bilateral active
      range of motion, and strength; in addition, the Western Ontario Shoulder
      Instability Index (WOSI), the Rowe Score, and the Subjective Shoulder Value (SSV)
      were obtained. Both an apprehension test and a relocation test were performed.
      Radiological imaging included bilateral radiographs (true anteroposterior and
      axillary view) to determine the grade of instability arthropathy. RESULTS: At
      final follow-up, a mean WOSI score of 295 (range, 0-1765), Rowe Score of 94
      (range, 55-100), SSV of 90% (range, 20%-100%), and pain level of 0.5 (range, 0-4)
      were noted. Slight differences were detected in active range of motion between
      the affected and the contralateral side: flexion 178 degrees  vs 179 degrees  ( P
      = .325), abduction 177 degrees  vs 179 degrees  ( P = .225), external rotation 63
      degrees  vs 67 degrees  ( P = .048), high external rotation 77 degrees  vs 82
      degrees  ( P = .007), internal rotation 8.8 vs 9.4 points ( P = .017), and high
      internal rotation 70 degrees  vs 74 degrees  ( P = .026). No significant strength
      deficit of the affected side was noticed. In 1 patient, a traumatic redislocation
      with fracture of the bone graft was observed 6 weeks after index surgery. No
      further recurrences were found during the follow-up period. Negative apprehension
      and relocation tests were confirmed in 77% of the shoulders, while 23% were
      positive. At final follow-up, 9 shoulders showed no signs of instability
      arthropathy (26%), mild arthropathy was revealed in 22 shoulders (63%), moderate
      arthropathy was noted in 3 shoulders (9%), and signs of severe arthropathy were
      found in 1 shoulder (3%) (collective instability arthropathy score, 0.9). The
      collective instability arthropathy score on the contralateral side was 0.4 +/-
      0.8 with no instability arthropathy in 24 shoulders (69%), mild arthropathy in 8
      shoulders (23%), moderate signs of arthropathy in 2 shoulders (6%), and severe
      arthropathy in 1 shoulder (3%) at the time of follow-up examination (collective
      instability arthropathy score, 0.4). The overall difference between affected
      shoulders and contralateral shoulders was significant ( P = .005). CONCLUSION:
      The J-bone graft procedure for the treatment of recurrent anterior shoulder
      instability shows excellent results regarding stability and function after a mean
      follow-up period of 18 years. However, the development of instability arthropathy
      of the affected shoulder is not prevented by this procedure.

PMID- 30207742
TI  - Development of nanoparticulate systems with action in breast and ovarian cancer:
      nanotheragnostics.
AB  - The use of nanoparticulate systems with action in breast and ovarian cancer has
      been highlighted in recent years as an alternative to increasing the therapeutic
      index of conventional anticancer drugs. Thus, nanoparticles have advantageous
      characteristics in the treatment of cancer. Several nanocarriers of drugs and
      nanoparticles are described in the literature. The pharmacokinetics of the drugs
      can be modified by the use of nanocarriers, which in turn facilitate the specific
      delivery of the drug to the tumour cell. Therefore, the present work is a review
      that examines some nanosystems with nanoparticles for action in the treatment of
      breast cancer and ovarian cancer.

PMID- 30207743
TI  - The roles and mechanisms of G3BP1 in tumour promotion.
AB  - Ras-GTPase-activating protein SH3 domain-binding protein 1 (G3BP1) is a SH3
      domain-binding protein that is overexpressed in a variety of tumour tissues and
      cancers, such as head and neck cancer, lung cancer, prostate cancer, colon cancer
      and breast cancer. G3BP1 promotes tumour cell proliferation and metastasis and
      inhibits apoptosis by regulating the Ras, TGF-beta/Smad, Src/FAK and p53
      signalling pathways. At present, polypeptides targeting G3BP1 have shown anti
      tumour activity and G3BP1 also involved in anti-cancer effects of some
      polyphenolic compounds (resveratrol and EGCG). Therefore G3BP1 may be a potential
      target for tumour treatment.

PMID- 30207744
TI  - Xenogeneic bone matrix immune risk assessment using GGTA1 knockout mice.
AB  - Homeotransplantation of bones for replacement therapy have been demonstrated
      reliably in clinical data. However, human donor bones applicable for
      homeotransplantation are in short supply, which facilitates the search for
      suitable alternatives, such as xenografts grafts. The alpha-Gal antigen-related
      immune risk of xenografts directly affects the safety and effectiveness of the
      biomaterials and limits their applications in the clinic. The immune risk can be
      prevented by depletion or breaking anti-Gal antibody prior to transplant.
      Therefore, how to assess the immune risk of the bone substitutes and select the
      reliable animal research model become extremely important. In this study, we
      prepared lyophilized bone substitutes (T1) and Guanghao Biotech bone substitutes
      (T2, animal-derived biomaterials with alpha-Gal antigen decreased), aimed to
      assess the immune risk of xenografts bone substitutes on GGTA1 knockout mice. The
      alpha-Gal antigen contents of T1 and T2 were firstly detected by ELISA method in
      vitro. The bone substitutes were then implanted subcutaneously into GGTA1
      knockout mice for 2, 4 and 12 weeks, respectively. The total serum antibody
      levels, anti-alpha-Gal antibody levels, inflammatory cytokine and splenic
      lymphocyte surface molecules were detected and histology analysis of skin and
      thymus were performed to systematically evaluate the immune response caused by
      the T1 and T2 bone substitutes in mice. In vitro results showed that the amount
      of alpha-Gal epitopes in T1 bone substitutes was significantly higher than T2
      bone substitutes, and the clearance rate of alpha-Gal antigen in T2 bone
      substitutes achieved about 55.6%. Results of antibody level in vivo showed that
      the T1 bone substitutes group possessed significantly higher total IgG, IgM, IgA
      and anti-alpha-Gal IgG levels than T2 and control group, while T2 group showed no
      significant changes of these indexes compared with control. In terms of
      inflammatory cytokines, T1 bone substitutes showed evidently higher levels of IL
      4, IL-12P70 and IL-10 than T2 and control, while T2 group was comparable to
      control. No changes in the levels of splenic lymphocyte surface molecules were
      found in the three groups (T1, T2 and control group) during the experimental
      periods. The pathological results demonstrated that the inflammatory response in
      T2 group was lighter than the T1 group, which was in accordance with the
      inflammatory cytokines levels. The above results indicated that the process of
      antigen removal effectively reduced the alpha-Gal antigens content in T2 bone
      substitutes, which caused little immune response in vivo and could be used as
      bone healing materials. This study also demonstrated that GGTA1 knockout mice can
      be used as a routine tool to assess the immune risk of animal-derived
      biomaterials.

PMID- 30207745
TI  - Alive attenuated Salmonella as a cargo shuttle for smart carrying of gold
      nanoparticles to tumour hypoxic regions.
AB  - In the present study, alive attenuated Salmonella typhi Ty21a was introduced as a
      vehicle for smart delivery of gold nanoparticles to the tumours' hypoxic regions.
      At the first step, the uptakes of gold nanoparticles with seven different
      decorations by S. typhi Ty21a was investigated using flow cytometry and
      inductively coupled plasma optical emission spectroscopy. The analyses
      demonstrated that folic acid functionalised gold nanoparticles (FA-GNPs) are the
      best candidates for producing the Golden Bacteria (GB). Subsequently, the GB and
      FA-GNPs efficacies for tumour targeting were investigated after intravenous
      injection to CT-26 tumour-bearing mice. The GB exhibited more GNPs delivery to
      the tumour in comparison with FA-GNPs. Moreover, GB injection causes more
      delivery of GNPs to the tumours' central regions in comparison with tumours'
      periphery. This trend is completely in reverse for FA-GNPs injected group. The
      ratios of peripheral to central regions' gold concentration of the tumours were
      1.95 +/- 0.13 and 0.61 +/- 0.10 for FA-GNPs and GB groups, respectively. This
      observation demonstrates higher accumulation of gold nanoparticles in the centre
      of the tumour due to their active delivery by the S. typhi Ty21a to the deeps of
      tumours.

PMID- 30207746
TI  - Domestic canaries (Serinus canaria forma domestica) are susceptible to low
      pathogenic avian influenza virus infections.
AB  - Avian influenza viruses have been isolated from many bird species; however,
      little is known about the susceptibility of pet birds to low pathogenic avian
      influenza (LPAI) viruses. To address this research gap, domestic canaries
      (Serinus canaria forma domestica) were experimentally infected with H5 and H7
      LPAI viruses to determine susceptibility and to evaluate samples for diagnostic
      purposes. Clinical evidence of infection (e.g. ruffled plumage and apathy) and
      mortality were noted for the canaries inoculated with chicken-adapted LPAI
      viruses. Real-time reverse transcription-polymerase chain reaction (RRT-PCR)
      demonstrated higher viral RNA levels in buccal compared to faecal samples. No
      clinical signs or mortality were observed in canaries inoculated with LPAI virus
      originating from wild birds; however, the canaries in this group did have
      evidence of viral RNA in buccal and faecal samples. Overall, this study showed
      that domestic canaries are susceptible to LPAI virus infections and that they can
      shed large amounts of viral RNA, primarily through the respiratory route. Thus,
      buccal swabs might be better samples than faeces for efficient detection of some
      LPAI virus infections in these birds. Although canaries have not been identified
      as a significant reservoir for LPAI viruses, they may be infected by LPAI
      viruses. Thus, the importance of the control of domestic canaries for detection
      of LPAI viruses should not be underestimated, especially in the contexts of
      international commercial exchange and outbreaks. RESEARCH HIGHLIGHTS Canaries are
      susceptible to infection with H5/H7 LPAI viruses. Canaries inoculated with LPAI
      viruses excrete large amounts of viral RNA. Buccal swabs may be appropriate
      specimens for AI virus detection in canaries. The control of canaries for LPAI
      virus detection should not be overlooked.

PMID- 30207747
TI  - A Novel Variant of Desmoplakin Is Potentially Associated with Silicosis Risk.
AB  - Two genome-wide association studies and one sequencing study have coincidently
      reported significant associations of single nucleotide polymorphisms (SNPs) in
      the desmoplakin (DSP) gene with the risk of pulmonary fibrosis (mainly idiopathic
      pulmonary fibrosis). However, these findings have not been well generalized to
      occupational pulmonary fibrosis (e.g., silica-related silicosis). We
      systematically genotyped 8 potentially functional SNPs and the previously
      reported rs2076295 and rs2744371 in DSP gene region and evaluated the
      associations between these 10 SNPs and silicosis risk in a case-control study
      that included 177 silicosis cases and 204 controls with similar numbers of silica
      dust exposure years as the cases from a Chinese population. Genotyping was
      performed using the improved multiligase detection reaction multiplex SNP
      genotyping system. The variant A allele of rs2076304 exhibited significant
      association with the risk of silicosis (odds ratio = 1.53, 95% confidence
      interval = 1.03-2.29, p = 0.036). Moreover, significant association was observed
      between different genotypes of rs2076304 and DSP expression (p = 1.1 * 10-7) in
      383 normal lung tissues. Further functional annotation indicated that the
      rs2076304 might influence the binding of RHOXF1. The rs2076304 in DSP gene is
      associated with a significantly increased risk of silicosis in a Han Chinese
      population. Further studies are warranted to validate and extend our findings,
      especially the biological mechanisms of rs2076304 in silicosis susceptibility.

PMID- 30207748
TI  - Improved Postprandial Glucose with Inhaled Technosphere Insulin Compared with
      Insulin Aspart in Patients with Type 1 Diabetes on Multiple Daily Injections: The
      STAT Study.
AB  - BACKGROUND: The majority of therapies have generally targeted fasting glucose
      control, and current mealtime insulin therapies have longer time action profiles
      than that of endogenously secreted insulin. The primary purpose of this study was
      to assess both glucose time-in-range (TIR: 70-180 mg/dL) and postprandial glucose
      excursions (PPGE) in 1-4 h using a real-time continuous glucose monitor (CGM)
      with Technosphere insulin (TI) versus insulin aspart in patients with type 1
      diabetes (T1DM) on multiple daily injections (MDI). RESEARCH DESIGN AND METHODS:
      This pilot, investigator-led, collaborative, open-label, multicenter, clinical
      research trial enrolled 60 patients with T1DM with HbA1c levels >=6.5% and <=10%.
      Individuals were randomized to treatment with titrated TI (n = 26) or titrated
      insulin aspart (n = 34), stratified by baseline HbA1c levels (<=8% or >8%). All
      were required to wear a real-time CGM throughout the trial. All patients in the
      TI group were advised to take supplemental inhalations at 1 and 2 h after meals
      if indicated based on postprandial glucose (PPG) values. The coprimary outcomes
      were assessed both in the full intent-to-treat population and in those
      individuals randomized to TI who were compliant with supplemental doses >=90% of
      the time (n = 15). The CGM data were analyzed using linear regression models.
      RESULTS: Overall, those treated with TI versus aspart achieved comparable TIR,
      but less time spent in hypoglycemia (<60 and <50 mg/dL, both P < 0.05). In the TI
      compliant group (n = 15), TIR was significantly greater (62.5% +/- 2.6% vs. 53.8%
      +/- 1.7%, P = 0.009) and time in hyperglycemia >180 mg/dL was lower (34.2% +/-
      2.7% vs. 41.0% +/- 1.7%, P = 0.045) as compared with the aspart group. PPG was
      also significantly lower in the TI cohort at 60 and 90 min postmeal, and PPGE
      were lower in the TI-compliant group as compared with the aspart group over 1-4-h
      postmeal (P < 0.05). In addition, there was weight gain in the aspart group
      compared with weight loss in the TI group (P = 0.006) despite higher prandial TI
      insulin dose. CONCLUSIONS: We conclude that using TI appropriately at mealtimes
      with supplemental dosing improves prandial glucose (TIR and 1-4 h) control
      without any increase in time in hypoglycemia or weight gain in patients with T1DM
      on MDI. The study results support a larger study using a treat-to-target design
      to confirm these findings. Clinical trial reg. no. NCT03143816,
      clinicaltrials.gov .

PMID- 30207749
TI  - Realisation of grammatical morphemes by children with phonological impairment.
AB  - The aim of this research was to explore how preschool-aged children with
      phonological impairment (PI) realise grammatical morphemes across different
      phonological contexts (i.e. singleton consonant, consonant cluster, syllable),
      conditions of finiteness and individual morpheme types. Factors accounting for
      children's realisation of grammatical morphemes were also examined. Eighty-seven
      Australian English-speaking preschoolers (aged 4-5 years) with PI completed the
      Children's Assessment of Morphophonology (CHAMP)-an elicited response task-in
      addition to standardised tests of speech and receptive language. The most
      challenging grammatical morphemes were finite morphemes (particularly past tense)
      and grammatical morphemes realised in consonant clusters. The ability to produce
      consonant clusters in single words significantly accounted for children's ability
      to realise grammatical morphemes, regardless of whether grammatical morphemes
      were realised in singleton, consonant cluster or syllable contexts. Realisation
      of grammatical morphemes by preschoolers with PI is influenced by phonological
      and morphological factors. The findings have implications regarding the
      assessment and differential diagnosis of preschoolers with concomitant
      phonological and language difficulties.

PMID- 30207750
TI  - Effect of Ramadan fasting on feelings, dietary intake, rating of perceived
      exertion and repeated high intensity short-term maximal performance.
AB  - : The present study was designed to investigate the effect of Ramadan fasting on
      feelings, dietary intake, rating of perceived exertion (RPE) and repeated high
      intensity short-term maximal performance. Thirteen physically active men (age:
      21.2 +/- 2.9 years, height: 175.6 +/- 5.6 cm, body-mass: 72.4 +/- 8.6 kg)
      performed a 5-m shuttle run test (6 * 30-s + 35-s of recovery in-between) during
      five experimental periods: fifteen days before Ramadan (BR), the first ten days
      of Ramadan (FR), the last ten days of Ramadan (ER), ten days after Ramadan (AR10)
      and 20 days after Ramadan (AR20). The study was carried out in Tunisia during the
      2016 Ramadan month. During the 5-m shuttle run test, higher distance (HD), total
      distance (TD) and fatigue index (FI) were recorded. RPE was determined after a 5
      min warm-up and after each repetition of the 5-m shuttle run test (the mean RPE
      score during the test was calculated). Moreover, a feelings scale (FS) was used
      after the warm-up and after the end of the 5-m shuttle run test. During the five
      experimental periods, dietary intake was assessed. The results showed that HD, TD
      and FI during the 5-m shuttle run test were not affected by Ramadan observance (p
      > 0.05). Likewise, FS scores recorded after the warm-up and the 5-m shuttle run
      test were not affected by Ramadan fasting (p > 0.05). However, mean RPE scores
      during the 5-m shuttle run test were significantly lower at ER (4.06 UA), AR10
      (3.86 UA) and AR20 (3.71 UA) in comparison to BR (4.51 UA) (p < 0.05). The
      results showed also that Ramadan fasting has no adverse effect on energy intake,
      protein (g and %), fat (g and %) and carbohydrate (g). However, the fractional
      contribution of carbohydrate was significantly higher AR10 than FR (53.1% vs.
      45.8%) and ER (53.1% vs. 46.5%) and AR20 than FR (5.92% vs. 45.8%) (p < 0.05). In
      conclusion, Ramadan fasting has no adverse effect on feelings, dietary intake,
      and short-term maximal performance. However, the RPE during repeated high
      intensity short-term maximal exercise was reduced AR20 in comparison to ER.
      ABBREVIATIONS: AR: After Ramadan; AR10: Ten days after Ramadan; AR20: Twenty days
      after Ramadan; BR: Fifteen days before Ramadan; ER: Last ten days of Ramadan; FI:
      Fatigue index; FR: First ten days of Ramadan; FS: Feelings scale; HD: Higher
      distance; PSQI: The Pittsburgh Sleep Quality Index; RPE: Rating of Perceived
      Exertion Scale; TD: Total distance.

PMID- 30207751
TI  - Age at death in cohorts of middle-aged men followed-up until nearly extinction:
      the European areas of the Seven Countries Study.
AB  - OBJECTIVES: To describe age at death (AD) in ten cohorts of middle-aged men
      followed-up until nearly extinction as a function of personal characteristics
      measured at baseline. MATERIAL AND METHODS: Cohorts of men aged 40-59 years in
      five European countries (Finland, the Netherlands, Italy, Serbia, Greece) were
      examined and then followed-up for mortality during 45 (3 cohorts) or 50 years (7
      cohorts). Multiple linear regression (MLR) models were computed with AD as
      dependent variable and 35 personal characteristics as independent variables.
      RESULTS: Out of 7047 men, 6798 (96.5%) died in 45-50 years. Average AD was 74.4
      (median 75) years. Only five variables were significant in all the five countries
      when tested by MLR. By pooling together all countries and selecting variables by
      a stepwise technique, 20 were significant (p < .05): age at entry examination,
      being married, being a never smoker or an ex-smoker (versus current smokers),
      forced expiratory volume, high socio-economic status, arm circumference,
      subscapular skinfold, having moderate or vigorous physical activity (all with a
      positive relationship with AD); father early mortality, laterality/linearity
      index, high systolic blood pressure, high serum cholesterol, having a major
      cardiovascular disease, diabetes or chronic bronchitis (these with a negative
      relationship), while body mass index, subdivided into four classes, showed a
      parabolic relationship (versus a reference class). Each factor was associated
      with a difference of months or a few years to AD, while their combinations were
      associated with several years of greater or smaller AD. CONCLUSIONS: The
      availability of a relatively small number of risk factors measured in middle-aged
      men allows making rough estimates of AD as related to all-cause mortality during
      a follow-up of 50 years. AD is also a valuable metrics to describe past health in
      nearly extinct populations. Key messages We aimed at studying the age at death
      (AD) of middle-aged men of the European cohorts of the Seven Countries Study,
      followed-up 45-50 years until nearly extinction, as a function of personal
      characteristics measured at baseline. Multiple linear regression (MLR) models
      were computed with AD as dependent variable and 35 personal characteristics or
      risk factors as independent variables and only five were significant in all
      individual countries, whereas pooling together all countries, 20 variables were
      significant as selected by stepwise MLR. Each factor was associated with
      differences of months or a few years to AD, while their combinations were
      associated with several years of greater or smaller AD. AD is a valuable metrics
      to describe past health in nearly extinct populations: it might also be used to
      communicate years of life gained by preventive measures on modifiable variables.

PMID- 30207752
TI  - Systemic arterial hypertension but not IGF-1 treatment stimulates cardiomyocyte
      enlargement in neonatal lambs.
AB  - Although cardiomyocyte terminal differentiation is nearly complete at birth in
      sheep, very limited postnatal expansion of myocyte number may occur. The capacity
      of newborn cardiomyocytes to respond to growth stimulation by proliferation is
      poorly understood. Our objective was to test this growth response in newborn
      lambs using two different stimuli shown to induce strong responses in fetuses and
      adults: increased systolic load (Load) and insulin-like growth factor I (IGF-1).
      METHODS Vascular catheters and an inflatable aortic occluder were implanted in
      lambs. Hearts were collected for analysis at 18 days of age after a 7-day
      experiment, and compared to Control hearts. RESULTS Load hearts, but not IGF-1
      hearts, were heavier (P=0.001) due to increased mass of the LV, septum and left
      atrium (40-50%, P=0.004). Terminal differentiation and cell cycle activity were
      not different between groups. Myocyte length was 7% greater in Load lamb hearts
      (P<0.05), and binucleated myocytes, which comprise ~90% of LV cells, were 25%
      larger in volume (P=0.03). Myocyte number per gram of myocardium was decreased in
      all ventricles of Load lambs (P=0.01). Cells from the IGF-1 group were not found
      to be different by any comparison. CONCLUSIONS These results suggest that the
      newborn sheep LV responds to systolic stress with cardiomyocyte hypertrophy, not
      proliferation. Further, IGF-1 is ineffective at stimulating cardiomyocyte
      proliferation at this age (despite effectiveness prior to birth). Thus to expand
      cardiomyocyte number in the newborn heart, therapies other than systolic pressure
      load and IGF-1 treatment need to be developed.

PMID- 30207753
TI  - Editorial: New Investigator Review Awardees 2018.

PMID- 30207754
TI  - Placental insufficiency contributes to fatty acid metabolism alterations in aged
      female mouse offspring.
AB  - Intrauterine growth restriction (IUGR) is an accepted risk factor for metabolic
      disorders in later life, including obesity and type 2 diabetes. The level of
      metabolic dysregulation can vary between subjects and is dependent on the
      severity and the type of IUGR insult. Classical IUGR animal models involve
      nutritional deprivation of the mother or uterine artery ligation. The latter aims
      to mimic a placental insufficiency, which is the most frequent cause of IUGR. In
      this study, we investigated whether IUGR due to placental insufficiency impacts
      the glucose and lipid homeostasis at advanced age. Placental insufficiency was
      achieved by deletion of the transcription factor AP-2y (Tfap2c), which serves as
      one of the major trophoblast differentiation regulators. TdelT-IUGR mice were
      obtained by crossing mice with a floxed Tfap2c allele and mice with Cre
      recombinase under the control of the Tpbpa promoter. In advanced adulthood (9-12
      months) female and male IUGR mice are respectively 20% and 12% leaner compared to
      controls. At this age, IUGR mice have unaffected glucose clearance and lipid
      parameters (cholesterol, triglycerides and phospholipids) in the liver. However,
      female IUGR mice have increased plasma free fatty acids (FFAs) (+87%) compared to
      controls. This is accompanied by increased mRNA levels of fatty acid synthase and
      endoplasmic reticulum stress markers in white adipose tissue. Taken together, our
      results suggest that IUGR by placental insufficiency may lead to higher
      lipogenesis in female mice in advanced adulthood, at least indicated by greater
      Fasn expression. This effect was sex-specific for the aged IUGR females.

PMID- 30207755
TI  - Intracranial pressure influences the level of sympathetic tone.
AB  - Sympathetic overdrive is associated with many diseases, but its origin remains an
      enigma. An emerging hypothesis in the development of cardiovascular disease is
      that the brain puts the utmost priority on maintaining its own blood supply; even
      if this comes at the "cost" of high blood pressure to the rest of the body. A
      critical step in making a causative link between reduced brain blood flow and
      cardiovascular disease is how changes in cerebral perfusion affect the
      sympathetic nervous system. A direct link between decreases in cerebral perfusion
      pressure and sympathetic tone generation in a conscious large animal has not been
      shown. We hypothesized that there is a novel control pathway between
      physiological levels of intracranial pressure (ICP) and blood pressure via the
      sympathetic nervous system. Intracerebroventricular infusion of saline produced a
      ramped increase in ICP of up to 20 mmHg over a 30-minute infusion period
      (baseline 4.0+/-1.1 mmHg). The ICP increase was matched by an increase mean
      arterial pressure such that cerebral perfusion pressure remained constant. Direct
      recordings of renal sympathetic nerve activity indicated that sympathetic drive
      increased with increasing ICP. Ganglionic blockade, by hexamethonium, preventing
      sympathetic transmission, abolished the increase in arterial pressure in response
      to increased ICP and was associated with a significant decrease in cerebral
      perfusion pressure. This is the first study to show that physiological elevations
      in intracranial pressure regulate renal sympathetic activity in conscious
      animals. We have demonstrated a novel physiological mechanism linking ICP levels
      with sympathetic discharge via a possible novel intracranial baroreflex.

PMID- 30207757
TI  - Ebola Virus Disease Preparations Do Not Protect the United States Against Other
      Infectious Outbreaks.

PMID- 30207758
TI  - Population Health Science as the Basic Science of Public Health: A Public Health
      of Consequence, October 2018.

PMID- 30207759
TI  - News From The Nation's Health.

PMID- 30207760
TI  - Public Health 3.0: Supporting Local Public Health in Addressing Behavioral
      Health.

PMID- 30207761
TI  - Work-Related Lung Cancer: The Practitioner's Perspective.

PMID- 30207762
TI  - Health Communication Trolls and Bots Versus Public Health Agencies' Trusted
      Voices.

PMID- 30207763
TI  - The Pregnancy Risk Assessment Monitoring System (PRAMS): Current Strengths and
      Opportunities for Growth.

PMID- 30207764
TI  - The Future of Maternal and Child Health Data in the United States.

PMID- 30207765
TI  - China's New Road for Tobacco Control: Tobacco Crop Substitution.

PMID- 30207766
TI  - Pregnancy Risk Assessment Monitoring System for Dads: Public Health Surveillance
      of New Fathers in the Perinatal Period.

PMID- 30207767
TI  - AJPH Global News.

PMID- 30207769
TI  - The First Comprehensive Program for Opioid Use Disorder in a US Statewide
      Correctional System.

PMID- 30207768
TI  - Differential Media Reporting of Unintentional Child Deaths in Chicago, 2011-2015.

PMID- 30207770
TI  - Paying the Hidden Bill: How Public Health Can Support Older Adults and Informal
      Caregivers.

PMID- 30207771
TI  - The Fateful Cohorts.

PMID- 30207772
TI  - Li et al. Respond.

PMID- 30207773
TI  - Is a Reduction in Access to Prescription Opioids the Cure for the Current Opioid
      Crisis?

PMID- 30207775
TI  - Decreased Food and Water Intake Attributable to Failing Sanitation in the United
      States.

PMID- 30207774
TI  - The Occupational Dimension of Lung Cancer Screening.

PMID- 30207776
TI  - Expedited Partner Therapy: Combating Record High Sexually Transmitted Infection
      Rates.

PMID- 30207778
TI  - We Cannot Treat the Dead.

PMID- 30207777
TI  - Interpreting Gaps Along the Preexposure Prophylaxis Cascade and Addressing
      Vulnerabilities to Stigma.

PMID- 30207779
TI  - Lung Cancer Screening: A Cost-Effective Public Health Imperative.

PMID- 30207780
TI  - Predictable, Preventable, and Deadly: Epidemic Carbon Monoxide Poisoning After
      Storms.

PMID- 30207781
TI  - One Screening for Ischemic Heart Disease, Lung Cancer, and Chronic Obstructive
      Pulmonary Disease: A Systems Biology Bridge for Tobacco and Radiation Exposure.

PMID- 30207782
TI  - Activation of TRPV1 channels leads to stimulation of NKCC1 cotransport in the
      lens.
AB  - Lens ion homeostasis is crucial in maintaining water content and, in turn,
      refractive index and transparency of the multicellular syncytium-like structure.
      New information is emerging on the regulation of ion transport in the lens by
      mechanisms that rely on Transient Receptor Potential Vanilloid (TRPV) ion
      channels. We found recently that TRPV1 activation leads to Ca2+/PKC-dependent
      ERK1/2 signaling. Here we show that the TRPV1 agonist capsaicin (100 nM) and
      hyperosmotic solution (350 vs 300 mOsm) similarly cause an increase of bumetanide
      inhibitable Rb uptake by intact porcine lenses and NKCC1 phosphorylation in the
      lens epithelium. The TRPV1 antagonist A889425 (1 uM) abolished the increases of
      Rb uptake and NKCC1 phosphorylation in response to hyperosmotic solution.
      Exposing lenses to hyperosmotic solution in the presence of MEK/ERK inhibitor
      U0126 (10 uM) or the WNK kinase inhibitor WNK463 (1 uM) also prevented NKCC1
      phosphorylation and the Rb uptake responses to hyperosmotic solution. WNK463 did
      not prevent the increase in ERK1/2 phosphorylation that occurs in response to
      capsaicin or hyperosmotic solution, suggesting ERK1/2 activation occurs prior to
      WNK activation in the sequence of signaling events. Taken together, the evidence
      indicates that activation of TRPV1 is a critical early step in a signaling
      mechanism that responds to a hyperosmotic stimulus, possibly lens shrinkage. By
      activating ERK1/2 and WNK, TRPV1 activation leads to NKCC1 phosphorylation and
      stimulation of NKCC1-mediated ion transport.

PMID- 30207783
TI  - Neurovascular unit transport responses to ischemia and common coexisting
      conditions: smoking and diabetes.
AB  - Transporters at the neurovascular unit (NVU) are vital for the regulation of
      normal brain physiology via ion, water, and nutrients movement. In ischemic
      stroke, the reduction of cerebral blood flow causes several complex
      pathophysiological changes in the brain one of which include alterations of the
      NVU transporters which can exacerbate stroke outcome by increased brain edema (by
      altering ion, water, and glutamate transporters), altered energy metabolism (by
      altering glucose transporters), and enhanced drug toxicity (by altering efflux
      transporters). Smoking and diabetes are common risk factors as well as coexisting
      conditions in ischemic stroke which are also reported to change the expression
      and function of NVU transporters. Coexistence of these conditions could cause an
      additive effect in terms of the alterations of brain transporters which might
      lead to worsened ischemic stroke prognosis and recovery. In this review, we have
      discussed the effects of ischemic stroke, smoking and diabetes on some essential
      NVU transporters and how the simultaneous presence of these conditions can affect
      the clinical outcome after an ischemic episode. Further scientific investigations
      are required to elucidate changes in NVU transport in cerebral ischemia which can
      lead to better, personalized therapeutic interventions tailor-made for these
      comorbid conditions.

PMID- 30207785
TI  - MicroRNA-488 inhibits progression of colorectal cancer via inhibition of mitogen
      activated protein kinase pathway by targeting claudin-2.
AB  - Colorectal cancer (CRC) affects people globally and lymph node metastasis (LNM)
      is an important indicator of poor clinical outcome in CRC. The current study aims
      to evaluate the role of microRNA-448 (miR-488) and claudin-2 (CLDN2) in
      epithelial-mesenchymal transition (EMT) and LNM of CRC through the MAPK signaling
      pathway. Firstly, microarray analysis indicated that MiR-488 was poorly expressed
      in CRC, whereas CLDN2 was highly expressed. Additionally, the bioinformatics
      website MicroRNA.org, and the dual luciferase reporter gene assay found that
      CLDN2 was a target gene of miR-488. Next, the results for the correlations
      between expression of miR-488 and clinicopathological characteristics of CRC
      indicated that the expression of miR-488 was closely associated with
      differentiation degree, LNM, and Dukes stages in CRC patients. Moreover, over
      expression of miR-488 inhibited the activation of the MAPK signal transduction
      pathway. Notably, loss- and gain- of-function experiments demonstrated that up
      regulation of miR-488 suppressed SW480 cell viability, invasion, and migration,
      and promoted apoptosis in SW480 cells. Finally, over-expression of miR-488
      inhibited LNM, MLVD, and tumor growth in nude mice. We conclude that over
      expression of miR-488 could suppress the cell proliferation, EMT, and LNM of CRC
      cells via inhibition of CLDN2-mediated MAPK signaling pathway, which could be a
      new molecular therapy target for CRC.

PMID- 30207786
TI  - Pembrolizumab for the first-line treatment of non-small cell lung cancer.
AB  - INTRODUCTION: Platinum-based chemotherapy had long played a role as standard
      therapy for the first-line treatment of advanced or recurrent non-small cell lung
      cancer (NSCLC). However, immune checkpoint inhibitors such as pembrolizumab, a
      monoclonal antibody that prevents programmed death protein 1 (PD-1) receptor,
      have brought a paradigm shift in this field. Areas covered: In this article, we
      review the relevant literatures and ongoing trials on the first-line treatment of
      pembrolizumab. Especially, in two pivotal phase III trials, KEYNOTE-024 and -189,
      both pembrolizumab monotherapy and combined pembrolizumab plus chemotherapy
      significantly prolonged overall survival (OS) compared to the existing platinum
      based chemotherapy. Currently, multiple trials with combination therapy of
      pembrolizumab and other agents have been conducted, and further evidences are
      expected to be created. Expert opinion: Immune checkpoint inhibitors that block
      the PD-1/PD-L1 pathway are essential drugs for advanced or recurrent NSCLC, among
      which pembrolizumab becomes one of the standards of care in the first-line of
      NSCLC. For further improvement in efficacy of pembrolizumab, it is necessary to
      clarify the identification of biomarkers exclusive to PD-L1 expression,
      predictive factors for patients who benefit most from the agent.

PMID- 30207784
TI  - SKELETAL MUSCLE ATROPHY AND DYSFUNCTION IN BREAST CANCER PATIENTS: ROLE FOR
      CHEMOTHERAPY-DERIVED OXIDANT STRESS.
AB  - How breast cancer and its treatments affect skeletal muscle is not well defined.
      To address this question, we assessed skeletal muscle structure and protein
      expression in 13 women diagnosed with breast cancer, who were receiving adjuvant
      chemotherapy following tumor resection, and 12 non-diseased controls. Breast
      cancer patients showed reduced single muscle fiber cross-sectional area (CSA) and
      fractional content of both sub-sarcolemmal and intermyofibrillar mitochondria.
      Drugs commonly used in breast cancer patients (doxorubicin and paclitaxel) caused
      reductions in myosin expression, mitochondrial loss and increased reactive oxygen
      species (ROS) production in C2C12 muscle myotube cell cultures, supporting a role
      for chemotherapeutics in the atrophic and mitochondrial phenotypes. Additionally,
      concurrent treatment of myotubes with mitochondrial-targeted antioxidant (MitoQ)
      prevented chemotherapy-induced myosin depletion, mitochondrial loss and ROS
      production. In patients, reduced mitochondrial content and size, and increased
      expression and oxidation of peroxiredoxin 3, a mitochondrial peroxidase, were
      associated with reduced muscle fiber CSA. Our results suggest that
      chemotherapeutics may adversely affect skeletal muscle in patients and that these
      effects may be driven through effects of these drugs on mitochondrial content
      and/or ROS production.

PMID- 30207787
TI  - Do Mound Height and Pitching Distance Affect Youth Baseball Pitching
      Biomechanics?
AB  - BACKGROUND: Pitching injuries continue to be a serious problem, with adolescents
      now representing the group with the most injuries. Some have proposed that
      lowering or eliminating the pitching mound in youth baseball may reduce joint
      stress and subsequent injuries. Another potential risk factor is advancing from
      youth to adult pitching distance without an intermediate distance. HYPOTHESES: It
      was hypothesized that for a group of young pitchers, pitching kinetics and
      kinematics would change with mound height. It was also hypothesized that pitching
      kinetics and kinematics would change with pitching distance. STUDY DESIGN:
      Controlled laboratory study. METHODS: Twenty-one young (12.6 +/- 0.5 years)
      baseball pitchers pitched 5 full-effort fastballs each from 5 different
      conditions, in random order: 14.02-, 16.46-, and 18.44-m distances from a 25 cm
      high mound, 16.46-m distance from a 15 cm-high mound, and 16.46-m distance from
      flat ground. Pitching biomechanical values were collected with a 12-camera
      automated motion capture system. Ball velocity and 31 other parameters were
      computed for each pitch. Data were compared between the 3 mound heights at 16.46
      m by use of repeated-measures analysis of variance and paired post hoc t tests (
      P < .05). Similarly, data were compared between the 3 distances from the 25-cm
      mound via repeated-measures analysis of variance and paired post hoc t tests ( P
      < .05). RESULTS: No differences were found in ball velocity, shoulder kinetics,
      or elbow kinetics associated with mound height. Ten kinematic parameters differed
      with mound height, including 8 parameters at lead foot contact. Maximum shoulder
      horizontal adduction torque and maximum shoulder anterior force increased with
      pitching distance. Only 3 kinematic parameters showed significant differences
      with pitching distance. CONCLUSION: The hypothesis that shoulder and elbow
      kinetics would change with mound height was not supported by the data. Several
      kinematic differences were found, but the majority were at lead foot contact
      before the rapid, dynamic phases of pitching. Change in pitching distance was
      associated with slight increase in shoulder kinetics as well as a few kinematic
      differences. CLINICAL RELEVANCE: Lowering or eliminating pitching mounds in youth
      baseball would not significantly decrease joint stress and injury risk to young
      pitchers. However, when available, transition from 14.02-m to 16.46-m to 18.44-m
      pitching distance may reduce stress on the young throwing shoulder.

PMID- 30207788
TI  - Implementation of a Peer Learning Program Replacing Score-Based Peer Review in a
      Multispecialty Integrated Practice.
AB  - OBJECTIVE: The aim of this study was to compare the efficacy of a peer learning
      program to score-based peer review in a radiology department. MATERIALS AND
      METHODS: Our score-based peer review program was transitioned to an open,
      inclusive, education- and improvement-oriented peer learning program. Program
      performance was evaluated by learning opportunity submissions, program
      participation, number of learning opportunity distributions to radiologists,
      number of practice improvement projects resulting from program, and radiologist
      survey results before and after interventions. RESULTS: Outcomes for the score
      based peer review program compared with those of the peer learning program were
      as follows. The mean number of radiologists participating monthly increased from
      5.0 to 35.2 (p < 0.01); submissions increased from 3.0 discrepancies per month to
      36.0 learning opportunities per month (p < 0.01); the mean monthly learning
      opportunity distributions to radiologists increased from 18 to 352 (p < 0.01);
      improvement projects performed during the study periods increased from 5 to 61 (p
      < 0.01); and mean monthly continuing medical education credits earned by
      radiologists increased from 7.7 to 50.6 (p < 0.01). Radiologists felt peer
      learning accomplished goals better than did score-based peer review. CONCLUSION:
      In transitioning our score-based peer review program to a peer learning program,
      our radiologists identified, discussed, and converted more learning opportunities
      into practice improvement and perceived peer learning to be of higher value than
      score-based peer review.

PMID- 30207789
TI  - Utility of Breast MRI for Further Evaluation of Equivocal Findings on Digital
      Breast Tomosynthesis.
AB  - OBJECTIVE: The purpose of this study is to evaluate the utility of MRI as a
      problem-solving tool for equivocal findings on diagnostic digital mammography
      (DM) and digital breast tomosynthesis (DBT). MATERIALS AND METHODS: Breast MRI
      examinations performed from March 2011 to November 2014 were retrospectively
      reviewed to identify those examinations that were performed to further assess
      equivocal findings on combined DM and DBT (DM/DBT) examinations. All patients
      underwent diagnostic ultrasound in conjunction with their DM/DBT examination.
      Imaging reports were retrospectively reviewed for BI-RADS findings and
      assessments of diagnostic DM/DBT and diagnostic MRI examinations. A review of the
      electronic medical records provided information on demographic data, cancer
      diagnoses, and pathologic findings. Differences in the positive predictive values
      and negative predictive values of DM/DBT and MRI were compared using a
      generalized estimating equation for correlated binary data. RESULTS: Of 5330 MRI
      examinations performed during the study, 67 (1%) were performed for evaluation of
      an equivocal finding, including 27 asymmetries (40%), 16 focal asymmetries (24%),
      five masses (7%), and 19 architectural distortion (28%). MRI correlates were
      identified in 22 of 67 examinations (33%). Biopsies yielded a cancer diagnosis
      for five of 67 patients (7%). For MRI, the positive predictive value and negative
      predictive value were 19% and 98%, respectively, whereas for DM/DBT they were 6%
      and 90%, respectively (p = 0.009 and p = 0.059, respectively). The frequency of
      recommendations for breast MRI to evaluate equivocal findings decreased
      exponentially in the 3 years after DBT implementation. CONCLUSION: As clinical
      implementation of DBT becomes increasingly widespread, breast radiologists need
      an algorithm for addressing the small number of inconclusive findings that remain
      equivocal despite thorough DM/DBT and ultrasound examinations. Breast MRI is a
      useful adjunctive tool for these selected cases.

PMID- 30207790
TI  - Prognostic Value of Volume-Based Metabolic Parameters of 18F-FDG PET/CT in
      Uterine Cervical Cancer: A Systematic Review and Meta-Analysis.
AB  - OBJECTIVE: The purpose of this study is to perform a systematic review and meta
      analysis of volume-based 18F-FDG PET/CT parameters regarding the prognostic value
      of metabolic tumor volume (MTV) and total lesion glycolysis (TLG) in patients
      with uterine cervical cancer. MATERIALS AND METHODS: The PubMed and EMBASE
      databases were systematically searched until January 19, 2018. We included
      studies that evaluated pretreatment MTV or TLG as a prognostic factor in uterine
      cervical cancer with event-free (EFS) and overall survival (OS) as the endpoints.
      Effect sizes of the prognostic value of MTV and TLG were measured in terms of
      hazard ratio (HR) and were meta-analytically pooled. Multiple subgroup analyses
      stratified to clinicopathologic and PET/CT variables were performed to explore
      heterogeneity. RESULTS: Twelve studies including 660 patients were included.
      Prognoses were worse in patients with high MTV and TLG, with pooled HRs of 5.89
      (95% CI, 3.85-9.01; p < 0.00001) and 5.82 (95% CI, 3.62-9.35; p < 0.00001),
      respectively, for EFS and 6.62 (95% CI, 3.44-12.73; p < 0.00001) and 7.75 (95%
      CI, 3.48-17.27; p < 0.00001), respectively, for OS. At multiple subgroups
      analyses, the prognostic values of MTV and TLG for EFS were consistently
      significant, with pooled HRs of 5.08-7.30 and 4.80-15.83, respectively.
      CONCLUSION: Volume-based FDG PET/CT parameters were significant prognostic
      factors in patients with uterine cervical cancer. In spite of clinical and
      methodologic differences across the studies, patients with high MTV or TLG had a
      higher risk of adverse events or death.

PMID- 30207791
TI  - Radiation Exposure to the Sacroiliac Joint From Low-Dose CT Compared With
      Radiography.
AB  - OBJECTIVE: The primary objective of this study was to estimate the effective dose
      delivered to the sacroiliac joint (SIJ) from low-dose (LD) CT compared with that
      from radiography. Secondary objectives included evaluation of diagnostic quality
      of LD CT of the SIJ and development of a clinical protocol for LD CT of the SIJ.
      MATERIALS AND METHODS: Data from 36 patients (19 women, 17 men) undergoing LD CT
      for suspected renal colic were analyzed. Two effective dose estimates were
      calculated: one for the SIJ and another for an extended region from the iliac
      crest to 1 cm below the SIJ. Thirty-six anteroposterior pelvic and 36 SIJ view
      radiographs were age-, sex-, and body width-matched to CT scans. Effective dose
      from radiography was estimated using the method described in International
      Commission on Radiologic Protection Publication 60. RESULTS: Maximum effective
      dose to the SIJ from LD CT was less than 1 mSv in all cases, with a mean +/- SD
      of 0.42 +/- 0.18 mSv (range, 0.14-0.83 mSv), whereas mean dose to the extended
      region was 0.57 +/- 0.24 mSv (range, 0.19-1.11 mSv). Mean dose from SIJ
      radiographs was 0.15 +/- 0.10 mSv (range, 0.07-1.38 mSv), and mean dose from a
      single pelvic radiograph was 0.09 +/- 0.06 mSv (range, 0.04-0.37 mSv). All CT
      studies were of diagnostic quality for assessment of the SIJ. CONCLUSION: LD CT
      of the SIJ can be consistently performed with an effective radiation dose of less
      than 1 mSv. Because reliability and sensitivity of radiography for sacroiliitis
      is poor, we recommend that LD CT replace radiography for dedicated evaluation of
      the SIJ.

PMID- 30207792
TI  - Removal of T-Fasteners Immediately After Percutaneous Gastrostomy Tube Placement:
      Experience in 488 Patients.
AB  - OBJECTIVE: The purpose of this article is to evaluate the safety of T-fastener
      removal immediately after percutaneous gastrostomy tube placement by assessing
      difference in complication rates between early and delayed gastropexy removal.
      MATERIALS AND METHODS: A retrospective review was performed of the electronic
      medical records of all patients who underwent percutaneous gastrostomy at our
      institution from January 2015 to June 2017. A total of 722 patients successfully
      underwent gastrostomy tube insertion during this period. Two hundred twenty-two
      patients were excluded from analysis on the basis of our exclusion criteria.
      Twelve patients were lost to follow-up. The remaining patients were divided into
      two groups: group 1 included 350 patients who had their T-fasteners released
      immediately after gastrostomy, and group 2 included 138 patients whose T
      fasteners were left in place for 2 weeks. Electronic medical records were
      reviewed for postprocedure complications for up to 1 month. Complications were
      classified according to Society of Interventional Radiology classification.
      Statistical analysis was performed using a logistic regression model with
      calculation of odds ratios, power, p values, and 95% CIs. RESULTS: Seven (2.0%)
      major and 24 (6.8%) minor complications occurred in group 1. Two (1.4%) major and
      11 (7.9%) minor complications occurred in group 2. There was no statistically
      significant difference in complication rates between immediate and delayed
      gastropexy removal. CONCLUSION: In our study, immediate removal of T-fasteners
      was not associated with a higher complication rate.

PMID- 30207793
TI  - Thoracic Diseases With Musculoskeletal Manifestations and Vice Versa: A Review.
AB  - OBJECTIVE: The purpose of this article is to review several thoracic conditions
      that are associated with certain musculoskeletal radiological abnormalities using
      imaging of patients with concomitant chest and musculoskeletal manifestations as
      illustrative examples. CONCLUSION: Radiologic findings of many thoracic diseases
      are often nonspecific. When standing alone, their interpretation commonly results
      in long differential diagnosis. However, in certain instances, a reasonably
      accurate diagnosis can be made based on imaging findings alone.

PMID- 30207794
TI  - Can Adrenal Adenomas Be Differentiated From Adrenal Metastases at Single-Phase
      Contrast-Enhanced CT?
AB  - OBJECTIVE: The purpose of this study is to evaluate whether adrenal metastases
      can be reliably differentiated from adenomas at single-phase contrast-enhanced
      CT. MATERIALS AND METHODS: Sixty-one consecutive patients from a single
      institution lung cancer registry (40 metastases and 36 adenomas) who underwent
      single-phase contrast-enhanced CT at baseline diagnosis were retrospectively
      studied by two radiologists (blinded to the diagnoses) who independently
      evaluated four features previously described in adenomas: smooth margin, rim
      enhancement, central vein sign (preserved adrenal vein), and homogeneity (using a
      5-point Likert scale). A third radiologist measured size and attenuation and
      performed quantitative texture analysis. Comparisons were performed using chi
      square, logistic regression, and ROC analysis. RESULTS: Metastases were larger
      than adenomas (mean [+/- SD] 24 +/- 11 mm [range, 11-66 mm] vs 19 +/- 5 mm
      [range, 11-34 mm]; p = 0.012), with overlap between groups. Attenuation of
      metastases and adenomas did not differ significantly (58.2 +/- 21.0 HU [range,
      21.0-108.0] vs 55.5 +/- 21.5 HU [range, 14.0-105.0]; p = 0.582). Skewness and
      kurtosis did not differ between groups (p = 0.612 and 0.978, respectively),
      whereas entropy was higher in metastases (p = 0.013). The AUC for entropy to
      diagnose metastases was 0.65 (95% CI, 0.52-0.77). Tumor margin, rim enhancement,
      and the central vein sign did not differ between groups (p > 0.05). Metastases
      were considered more heterogeneous by both radiologists (p = 0.001 and 0.011,
      respectively), and agreement was satisfactory (kappa = 0.51). Likert scores of 4
      or 5 (mostly or completely heterogeneous) yielded sensitivity and specificity for
      diagnosis of metastases of 32.5% and 97.2%, respectively, for radiologist 1 and
      22.5% and 97.2%, respectively, for radiologist 2. CONCLUSION: Adrenal metastases
      cannot be reliably differentiated from adenomas at single-phase contrast-enhanced
      CT. Increased tumor size and heterogeneity were specific findings but showed
      unacceptably low sensitivity.

PMID- 30207795
TI  - Generation of Functional Myocytes from Equine Induced Pluripotent Stem Cells.
AB  - Induced pluripotent stem cells (iPSCs) have revolutionized human biomedicine
      through their use in disease modeling and therapy. In comparison, little progress
      has been made toward the application of iPSCs in veterinary species. In that
      regard, skeletal myocytes from iPSCs would have great potential for understanding
      muscle function and disease in the equine athlete. In this study, we generated
      skeletal myotubes by transducing equine iPSC-derived mesenchymal derivatives with
      an inducible lentiviral vector coding for the human sequence of the myogenic
      factor, MyoD. Myosin heavy chain-positive myotubes generated from two different
      iPSC lines were compared to myotubes from adult equine skeletal muscle progenitor
      cells (MPCs). iPSC myotubes had a smaller mean area than MPC myotubes (<=2-fold).
      In addition, quantitative polymerase chain reaction analyses showed that iPSC
      myotubes expressed MYH2 and MYH3 isoforms (at similar or lower levels than MPC
      myotubes), but they did not express the mature muscle isoform, MYH1. Compared to
      MPC myotubes, iPSC myotubes expressed reduced levels of the myogenic factors,
      MYOD1 and MYF6, but did not express MYF5. Finally, iPSC myotubes responded to KCl
      induced membrane depolarization by releasing calcium and did so in a manner
      similar to MPC myotubes. In conclusion, this is the first study to report the
      generation of functional myocytes from equine iPSCs.

PMID- 30207796
TI  - Serotonin 3 receptor signaling regulates 5-fluorouracil-mediated apoptosis
      indirectly via TNF-alpha production by enhancing serotonin release from
      enterochromaffin cells.
AB  - Antagonists of the 5-hydroxytryptamine (serotonin) 3 receptor (5-HT3R) have anti
      inflammatory and anti-apoptotic activities, but the detailed, underlying
      mechanisms are not well understood. We focused on anti-apoptotic activities via 5
      HT3R signaling to clarify the underlying mechanisms. Mice were administered 5
      fluorouracil (5-FU), which induced apoptosis in intestinal epithelial cells.
      Coadministration with 5-HT3R antagonists or agonists tended to decrease or
      increase the number of apoptotic cells, respectively. In serotonin 3A receptor (5
      HT3AR) null (HTR3A-/-) mice, the number of apoptotic cells induced by 5-FU was
      decreased compared with that in wild-type (WT) mice. Bone marrow (BM)
      transplantation was performed to determine if BM-derived immune cells regulated 5
      FU-induced apoptosis, but they were found to be unrelated to this process. Data
      from 5-HT3AR/enhanced green fluorescent protein reporter mice revealed that 50%
      of enterochromaffin (EC) cells expressed 5-HT3AR, but the number of apoptotic
      cells induced by 5-FU in the intestinal crypt organoids of HTR3A-/- mice was not
      altered compared with WT mice. In contrast, plasma 5-HT concentrations in WT mice
      but not in HTR3A-/- mice administered 5-FU were increased significantly. In
      conclusion, 5-HT3R signaling may enhance 5-HT release, possibly from EC cells
      intravascularly, or paracrine, resulting in increases in plasma 5-HT
      concentration, which in turn, enhances apoptotic activities induced by 5-FU.
      Mikawa, S., Kondo, M., Kaji, N., Mihara, T., Yoshitake, R., Nakagawa, T.,
      Takamoto, M., Nishimura, R., Shimada, S., Ozaki, H., Hori, M. Serotonin 3
      receptor signaling regulates 5-fluorouracil-mediated apoptosis indirectly via TNF
      alpha production by enhancing serotonin release from enterochromaffin cells.

PMID- 30207797
TI  - CD36-triggered cell invasion and persistent tissue colonization by tumor
      microvesicles during metastasis.
AB  - Tumor microvesicles are a peculiar type of extracellular vesicles that circulate
      in the blood of patients with metastatic cancer. The itineraries and immune cell
      interactions of tumor microvesicles during the intravascular and extravascular
      stages of metastasis are largely unknown. We found that the lipid receptor CD36
      is a major mediator of the engulfment of pancreatic tumor microvesicles by
      myeloid immune cells in vitro and critically samples circulating tumor
      microvesicles by resident liver macrophages in mice in vivo. Direct nanoscopic
      imaging of individual tumor microvesicles shows that the microvesicles rapidly
      decay during engulfment whereby their cargo is targeted concomitantly to the
      plasma membrane and the cytoplasm excluding lysosomal compartments. CD36 also
      promotes internalization of blood cell (nontumor) microvesicles, which involves
      endolysosomal pathways. A portion of tumor microvesicles circulating in the liver
      microcirculation traverses the vessel wall in a CD36-dependent way. Extravasated
      microvesicles colonize distinct perivascular Ly6C- macrophages for at least 2 wk.
      Thus, the microvesicles are increasingly integrated into CD36-induced
      premetastatic cell clusters and enhance development of liver metastasis. Hence,
      promotion of metastasis by pancreatic tumor microvesicles is associated with CD36
      regulated immune cell invasion and extravasation of microvesicles and persistent
      infiltration of specific tissue macrophages by microvesicle cargo.-Pfeiler, S.,
      Thakur, M., Grunauer, P., Megens, R. T. A., Joshi, U., Coletti, R., Samara, V.,
      Muller-Stoy, G., Ishikawa-Ankerhold, H., Stark, K., Klingl, A., Frohlich, T.,
      Arnold, G. J., Wormann, S., Bruns, C. J., Algul, H., Weber, C., Massberg, S.,
      Engelmann, B. CD36-triggered cell invasion and persistent tissue colonization by
      tumor microvesicles during metastasis.

PMID- 30207798
TI  - Iron overload by transferrin receptor protein 1 regulation plays an important
      role in palmitate-induced insulin resistance in human skeletal muscle cells.
AB  - Free fatty acid is considered to be one of the major pathogenic factors of
      inducing insulin resistance. The association between iron disturbances and
      insulin resistance has recently begun to receive a lot of attention. Although
      skeletal muscles are a major tissue for iron utilization and storage, the role of
      iron in palmitate (PA)-induced insulin resistance is unknown. We investigated the
      molecular mechanism underlying iron dysregulation in PA-induced insulin
      resistance. Interestingly, we found that PA simultaneously increased
      intracellular iron and induced insulin resistance. The iron chelator deferoxamine
      dramatically inhibited PA-induced insulin resistance, and iron donors impaired
      insulin sensitivity by activating JNK. PA up-regulated transferrin receptor 1
      (tfR1), an iron uptake protein, which was modulated by iron-responsive element
      binding proteins 2. Knock down of tfR1 and iron-responsive element-binding
      proteins 2 prevented PA-induced iron uptake and insulin resistance. PA also
      translocated the tfR1 by stimulating calcium influx, but the calcium chelator,
      BAPTA-AM, dramatically reduced iron overload by inhibiting tfR1 translocation and
      ultimately increased insulin sensitivity. Iron overload may play a critical role
      in PA-induced insulin resistance. Blocking iron overload may thus be a useful
      strategy for preventing insulin resistance and diabetes.-Cui, R., Choi, S.-E.,
      Kim, T. H., Lee, H. J., Lee, S. J., Kang, Y., Jeon, J. Y., Kim, H. J., Lee, K.-W.
      Iron overload by transferrin receptor protein 1 regulation plays an important
      role in palmitate-induced insulin resistance in human skeletal muscle cells.

PMID- 30207799
TI  - Substrate-induced conformational change in cytochrome P450 OleP.
AB  - The regulation of cytochrome P450 activity is often achieved by structural
      transitions induced by substrate binding. We describe the conformational
      transition experienced upon binding by the P450 OleP, an epoxygenase involved in
      oleandomycin biosynthesis. OleP bound to the substrate analog 6DEB crystallized
      in 2 forms: one with an ensemble of open and closed conformations in the
      asymmetric unit and another with only the closed conformation. Characterization
      of OleP-6DEB binding kinetics, also using the P450 inhibitor clotrimazole,
      unveiled a complex binding mechanism that involves slow conformational
      rearrangement with the accumulation of a spectroscopically detectable
      intermediate where 6DEB is bound to open OleP. Data reported herein provide
      structural snapshots of key precatalytic steps in the OleP reaction and explain
      how structural rearrangements induced by substrate binding regulate activity.
      Parisi, G., Montemiglio, L. C., Giuffre, A., Macone, A., Scaglione, A., Cerutti,
      G., Exertier, C., Savino, C., Vallone, B. Substrate-induced conformational change
      in cytochrome P450 OleP.

PMID- 30207800
TI  - Pharmacological management of depression in patients with multiple sclerosis.
AB  - INTRODUCTION: The pharmacotherapeutic management of depression in patients with
      multiple sclerosis (MS) is a matter of debate that cannot be decided from the
      evidence available in the current literature. Therefore, its management
      essentially relies on the clinical experience of the prescribing clinician rather
      than on evidence-based approaches. Areas covered: This review provides a
      clinically oriented critical perspective on the connection between MS and major
      depressive disorder (MDD) or depression associated with bipolar disorder (BD),
      focusing on its optimal pharmacotherapy. Both clinical and pharmacological
      considerations are accounted in order to promote rational pharmacotherapy, both
      in terms of efficacy and tolerability. Expert opinion: Despite its clinical
      burden and relatively frequent occurrence, the interplay of MS and depression
      still requires further controlled trials to better clarify the appropriate
      pharmacotherapy across varying 'diseases categories' of MS itself, as well as
      discriminating between depressive symptoms that do not necessarily reach the
      threshold of either MDD or BD. Additional insight into new mood-tolerated
      neurological pharmacotherapy for MS is likewise warranted toward a more
      effective, immune- and patient-tailored pharmacotherapy, while promoting
      innovation in drug design, with the ultimate goal of enhancing the overall
      quality life of the affected individual, his/her caregivers, and to reduce the
      associated economic and social burden.

PMID- 30207801
TI  - Primary central nervous system lymphoma with no enhancement initially and no
      significant progression over a long term: a case report and review of the
      literature.
AB  - Primary central nervous system lymphoma, a rare primary intracranial tumor, is
      highly malignant and usually associated with poor prognosis. Recent years, owing
      to the remarkable progress in intervention techniques, survival time reported has
      been significantly prolonged. Strategies targeting alleviation and remission are
      primarily depended on the early diagnosis. However, due to the heterogeneity of
      the clinical symptoms and imaging features, the disease is frequently
      misdiagnosed especially in the early phase, rendering a delay of optimal
      treatment. Herein, we reported the case of a 61-year-old man who was initially
      misdiagnosed as demyelinating encephalopathy. MRI images showed multifocal
      lesions across the cerebral cortex and deep white matter, which are not
      strengthened on contrast enhancements. In respect of clinical symptoms, no
      significant progress was observed over about 11 months. Finally, the diagnosis
      was revealed by brain biopsy. After reviewing all the images of the patient, we
      found that the corpus callosum was involved early in the course of the disease.
      Therefore, for multifocal intracranial lesions involving the corpus callosum, we
      should always be vigilant about the possibility of primary central nervous system
      lymphoma. Histopathological examination of brain biopsy is helpful for early
      definitive diagnosis.

PMID- 30207803
TI  - ILCA(r) News Brief: Working With International Collaborators to Change Our
      Communities and the World.

PMID- 30207802
TI  - Examination of the uses, needs, and preferences for health technology use in
      adolescents with asthma.
AB  - OBJECTIVE: To examine the health technology uses and preferences of adolescents
      with asthma using a qualitative descriptive individual interview approach.
      METHODS: Twenty adolescents were recruited from regularly scheduled asthma clinic
      appointments from February to July 2016. Patients were interviewed about their
      technology use and ways in which health technology could improve their asthma
      management using an open-ended semi-structured interview format. Interviews were
      audio recorded, transcribed, and coded into themes. RESULTS: Social media (e.g.
      Snapchat, Instagram) and general communication (e.g. messaging) were the most
      common uses of technology while medical reminders (e.g. appointment, refill,
      medication) were the most common use of health technology. Adolescents identified
      ways in which health technology could improve their asthma management including
      (1) tracking symptoms and medication, (2) medical reminders, and (3) asthma and
      self-management knowledge specifically related to medications and individual
      action plans. Other themes that emerged included a desire to customize health
      technology to fit with individual schedules and medical routines and use of
      health technology data with medical providers. CONCLUSIONS: Adolescents and
      parents experience a number of challenges related to managing asthma, and health
      technology interventions should focus on ways to improve adherence and self
      management. Future research considerations and potential interventions including
      ways to integrate adolescent preferences with evidence-based interventions are
      discussed.

PMID- 30207804
TI  - Ultra-Wide Field Imaging Characteristics of Primary Retinal Vasculitis: Risk
      Factors for Retinal Neovascularization.
AB  - AIM: To evaluate patterns of retinal vasculitis with ultra-wide field imaging
      (UWF) and ascertain the risk factors for retinal neovascularization. METHODS:
      Consecutive patients of retinal vasculitis were included prospectively. Patients
      with retinal vasculitis secondary to uveitis were excluded. UWF was done for all
      the patients. Retinal involvement was classified into three zones and area of
      capillary non-perfusion was stratified into clock hours. RESULTS: Two hundred
      patients were included, 85% (n = 170) were male. Mean age was 28.99 +/- 10.56
      years. Clinical examination revealed 65% cases (n = 130) to be bilateral, while
      UWF angiography detected 72.5% (n = 145) to have bilateral involvement. Retinal
      neovascularization was present in 47% (n = 188).Presence of posterior disease had
      very high odds ratio for development of retinal neovascularization as compared to
      cases restricted to retinal periphery (OR = 45.03, CI = 6.10-332.30, p = <
      0.001). CONCLUSION: UWF imaging is useful in detecting retinal vasculitis, which
      is otherwise obscure to clinical examination and assessing risk factors for
      retinal neovascularization.

PMID- 30207805
TI  - Fetal and Placental Pathology in Congenital Syphilis: A Comprehensive Study in
      Perinatal Autopsy.
AB  - INTRODUCTION: At autopsy, without available serologic information, diagnosing
      congenital syphilis (CS) relies on identification of Treponema pallidum in
      tissues. Recognition of clues leading to detection of the organism is important.
      MATERIALS AND METHODS: Autopsy cases with CS were studied for fetal and placental
      abnormalities. RESULTS: Twenty-one cases were recruited: 12/21 with identifiable
      T. pallidum and 9/21 with positive serology and characteristics of CS. 20/21
      (95%) demonstrated >=1 fetal abnormalities. Chronic stress involution of thymus
      was most common. Hydrops and hepatosplenomegaly were found in >50%. Metaphyseal
      abnormalities and organ inflammation were found in <30%. Mucocutaneous lesions
      were lacking. Placental abnormalities were identified in 20/21 (95%).
      Placentomegaly was most common. Amniotic fluid infection (AFI) was noted in >50%.
      CONCLUSION: Common findings in CS at autopsy include chronic stress involution of
      thymus, hydrops, and hepatosplenomegaly. Mucocutaneous lesions are uncommon.
      Common placental findings in fetal deaths due to CS include placentomegaly and
      AFI.

PMID- 30207806
TI  - Application of a new fractional radiofrequency device in the treatment of
      photoaging skin in Chinese patients.
AB  - BACKGROUND AND OBJECTIVES: Fractional radiofrequency (FRF) has been used in the
      treatment of photoaged skin for a long time. This study was intended to examine
      the efficacy and safety of electrode pin FRF in the treatment of photoaged skin
      in Chinese patients. MATERIALS AND METHODS: Twenty healthy Chinese subjects with
      facial photoaged skin were enrolled in this study. Each subject received three
      FRF treatments at 4-week intervals. Changes of photoaging were analyzed by a
      global evaluation, subjective Assessment, a Mexameter, and VISIA. RESULTS: In
      total, 12 of 18 patients (66.7%) and 11 of 18 patients (61.1%) had good or
      excellent improvement respectively according to investigator A and investigator
      B. Also, 13 of 18 patients (72.2%) rated their satisfaction of the overall
      improvement as satisfied or very satisfied. Mean melanin index and erythema index
      values significantly decreased between baseline and 12-week follow up (P < 0.05).
      The average wrinkle percentile was increased at 12-week follow-up (79.0 +/- 8.4)
      compared to baseline (58.8 +/- 10.2). Adverse effects were limited to erythema,
      tiny scabs and mild pain. CONCLUSIONS: FRF is a safe and effective method for
      photoaging skin in Chinese patients.

PMID- 30207807
TI  - A phase 2, multicenter, double-blind, randomized, vehicle-controlled clinical
      study to compare the safety and efficacy of a halobetasol propionate 0.01% lotion
      and halobetasol propionate 0.05% cream in the treatment of plaque psoriasis.
AB  - BACKGROUND: Halobetasol propionate (HP) 0.05% is a highly effective short-term
      treatment for plaque psoriasis. OBJECTIVE: Compare efficacy and safety of once
      daily HP 0.01% lotion and 0.05% cream (Ultravate(r)) in moderate-to-severe
      psoriasis. METHODS: Multicenter, randomized, double-blind, vehicle-controlled
      Phase 2 study (N = 150). Patients randomized to HP 0.01% lotion, HP 0.05% cream,
      or vehicle, once-daily for 2 weeks. Efficacy assessments included treatment
      success; impact on erythema, plaque elevation, and scaling; and improvement in
      body surface area (BSA). Safety and treatment-emergent adverse events (TEAEs)
      were evaluated throughout. RESULTS: 30.0% and 31.6% of patients were treatment
      successes with HP 0.01% lotion and HP 0.05% cream (p = .854). A 2-grade
      improvement in erythema, plaque elevation and scaling was achieved in 38.3%,
      40.0%, and 43.3% of patients, compared with 31.6% (p = .446), 36.8% (p = .727),
      and 47.4% (p = .663) on HP 0.05% cream. BSA improved by 22.3% with HP 0.01%
      lotion compared with 20.9% (p = .787). There was one treatment-related
      application-site reaction with HP 0.01% lotion, and no AE reports of skin
      atrophy, striae, telangiectasia, or folliculitis. CONCLUSIONS: Halobetasol
      propionate 0.01% lotion was comparable to the higher concentration halobetasol
      propionate 0.05% cream; achieving treatment success, reducing psoriasis signs at
      the target lesion, and improving BSA following two weeks' daily-treatment. Both
      treatments were well-tolerated. CLINICAL TRIALS REGISTRATION: clinicaltrials.gov
      NCT02785185.

PMID- 30207808
TI  - A survey on teamwork status in caring for patients with heart failure: A cross
      sectional study.
AB  - As a result of the complex nature of chronic heart failure (HF), these patients
      require an interprofessional team approach for care and treatment. This is
      because an interprofessional approach can manage resources more effectively and
      improve treatment efficacy. This research was done to evaluate the status of
      teamwork in caring for HF patients. In this cross-sectional study, the views of
      308 members of the care team were collected through the use of Team Assessment
      Questionnaire (TAQ). The mean and standard deviation of teamwork was 2.4 +/- 0.3.
      There was a significant difference between the teamwork status (total TAQ score)
      and age, gender and job experience (p < 0.05). The highest mean was for the team
      leadership dimension of the questionnaire (2.5 +/- 0.5) while the lowest was for
      team foundation (2.4 +/- 0.3). Results indicated that the status of teamwork is
      almost moderate. Teamwork in caring for HF patients was influenced by many
      factors, including age, gender, and job experience. Teamwork can be enhanced by
      establishing the equality of women and men's rights, continuous training and
      attention to proportional age and gender combinations.

PMID- 30207809
TI  - LA phonospirometry technique compared to pediatric respiratory assessment measure
      and peak expiratory flow measurement as a novel technique to assess the severity
      of an asthma exacerbation.
AB  - OBJECTIVE: Asthma is a common chronic disease treated in emergency departments.
      The measurements of Peak Expiratory Flow (PEF) and Pediatric Respiratory
      Assessment Measure (PRAM) scores have been recommended as objective techniques in
      the assessment of acute asthma exacerbations, but have multiple barriers limiting
      their use. The Los Angeles phonospirometry technique is an easier, trans-cultural
      technique. The technique assesses dyspnea by measuring how many seconds a child
      is able to chant "LA LA LA" in a single breath. The objective of this study is to
      determine the correlation of this technique with PEF measurements and PRAM scores
      in children with acute asthma exacerbations, both before and after nebulized
      bronchodilator treatment. METHODS: A convenient sample of children aged 5-17
      years being treated for asthma in the ED was enrolled. Phonospirometry, PRAM, and
      PEF measurements were obtained through pre and post inhaled bronchodilator
      treatments. The highest values from each measurement were correlated using
      Spearman's correlation coefficient. RESULTS: A total of 91 children were
      enrolled. The correlations at pre-treatment, after first, second, and third
      treatments between phonospirometry and PEF were 0.38 (p < 0.001), 0.60 (p <
      0.001), 0.54 (p < 0.001), 0.52 (p < 0.01), respectively; between phonospirometry
      and PRAM were -0.37 (p < 0.001), -0.42 (p < 0.001), -0.26 (p < 0.05), and -0.06
      (p > 0.05), respectively; and between PEF and PRAM were -0.6 (p < 0.01), -0.54 (p
      < 0.001), -0.38 (p < 0.01), and -0.36 (p - 0.05), respectively. CONCLUSIONS: This
      novel technique correlates mild to moderately with PEF, and shows promising aide
      in the assessment of children with acute asthma exacerbations.

PMID- 30207810
TI  - Outcomes of "Early" Withdrawal of Corticosteroid Sparing Immunomodulatory Therapy
      for Birdshot Retinochoroidopathy.
AB  - PURPOSE: To review early withdrawal of immunomodulatory therapy (IMT) for
      birdshot retinochoroidopathy (BSRC). DESIGN: Retrospective case-series of sixteen
      patients with Human-leukocyte-antigen-A29-positive BSRC treated with IMT >= 1
      year and discontinued prior to achieving durable remission, observed >= 6 months
      off IMT. RESULTS: Mean duration on IMT was 42.4 months. At discontinuation,
      quiescence was achieved in 75.0% of eyes. Subjects off IMT for 6 months, 1 year,
      and 3 years showed quiescence in 75.0%, 77.8%, and 80.0% of eyes. No
      significantly decreased vision was found 6 or 12 months after discontinuation.
      One eye experienced significantly decreased vision following 3 years without IMT.
      Significantly decreased amplitude on electroretinography and worse deviation
      parameters in perimetry were found in patients 3 years after withdrawal that
      experienced early discontinuation when compared with those achieving durable
      remission on IMT > 2 years (p < 0.05). CONCLUSION: The possibility of
      electroretinography and perimetry results worsening after early IMT
      discontinuation remained if the patients couldn't achieve remission.

PMID- 30207811
TI  - Analysis of 130 Cases of Sympathetic Ophthalmia - A Retrospective Multicenter
      Case Series.
AB  - OBJECTIVE: To analyze the demographic profile, treatment, and visual outcome of
      the patients with sympathetic ophthalmia (SO) in a multicenter collaborative
      retrospective cohort study. METHODS: Medical records of the patients with SO from
      UK, Singapore, India were reviewed for history of ocular trauma or surgery and
      subsequent development of uveitis consistent with SO, presenting symptoms,
      treatment, and visual outcomes. RESULTS: A total of 130 patients were diagnosed
      with SO during the study period. Eighty-one (62.3%) patients were men. The mean
      age was 48.4 +/- 15.5 years. The most common presenting symptom was blurring of
      vision (89.2%), followed by pain (29.2%) and floaters (23.8%). Ninety-two (70.7%)
      required additional immunosuppressive therapy. Thirty-six (27.9%) patients
      underwent enucleation of the inciting eye. CONCLUSIONS: SO is a potentially sight
      threatening disease with high rates of visual loss. It warrants prompt evaluation
      and treatment. With the advances and availability in immunotherapy, the visual
      prognosis is relatively good.

PMID- 30207812
TI  - Functional strength measurement in cerebral palsy: feasibility, test-retest
      reliability, and construct validity.
AB  - PURPOSE:  No instrument exists that measures functional strength in both lower
      and upper extremities in children with cerebral palsy (CP). Therefore, the
      functional strength measurement (FSM) was tested for feasibility, test-retest
      reliability and validity in CP. METHODS:  Thirty-seven children with CP (aged 4
      10 years, Gross Motor Function Classification System I and II) participated. The
      most common compensations for CP were described; new item descriptions were
      standardized, and one item was removed. Test-retest reliability was examined. To
      measure convergent validity, correlations between the FSM-CP and isometric muscle
      strength measured with the handheld dynamometer (HHD) were determined. RESULTS: 
      Test-retest reliability was considered high for all items (intra-class
      correlation coefficient 0.79-0.95). Significant correlations between the HHD and
      FSM-CP ranged from r = 0.36 to 0.75. CONCLUSION:  The FSM-CP is feasible,
      reliable, and valid to use in children with CP. The FSM-CP can be considered as a
      helpful tool in clinical practice of physical examination of children with CP.

PMID- 30207813
TI  - Evolution and species-specific conservation of toll-like receptors in terrestrial
      vertebrates.
AB  - Toll-like receptors (TLRs) are known for their essential roles in promotion of
      innate immunity and induction of adaptive immunity through recognition of
      pathogen-associated molecular patterns (PAMPs) or danger associated molecular
      patterns (DAMPs). TLR genes are excellent models for the study of the selective
      pressure enforced by microorganisms on the host genome. Phylogenetic analyses
      have shown that interactions between pathogens and immune systems have changed
      during evolution. Selective pressure for maintenance of specific pathogen
      recognition has led to evolution of TLRs under both positive and purifying
      selection. However, intracellular and cell-surface TLRs have been affected
      differently due to their variation in conservational constraints. In this review,
      we summarize some of the main studies on the influence of selection on shaping
      the evolution of several TLR gene families in different terrestrial vertebrate
      species. We also describe the effect of evolution on the function of different
      TLRs and their specific conservations in these species and show similarities and
      differences in evolutionary patterns of TLR orthologs among species as well as
      among TLR gene families.

PMID- 30207814
TI  - Perilla Oil Decreases Aortic and Hepatic Lipid Accumulation by Modulating
      Lipogenesis and Lipolysis in High-Fat Diet-Fed Mice.
AB  - Perilla oil has been shown to be beneficial for ameliorating metabolic disorders,
      but its protective effect is still controversial. We investigated the effect of
      perilla oil on obesity-induced hepatic and vascular changes in high-fat diet
      (HFD)-fed mice and provided underlying mechanisms for potential therapeutic
      applications. Tomato and paprika extract was added to prevent the oxidation
      during storage of perilla oil. HFD-fed mice were orally administered palm or
      perilla oil for 90 days. Food intake, body and liver weight, and serum
      cholesterol levels were measured. Arterial and hepatic lipid accumulation was
      determined by histological staining. Hepatic triglyceride levels and the
      expression of proteins regulating lipid metabolism were analyzed. Food intake and
      body weight were not different between palm oil-treated and perilla oil-treated
      mice. Serum cholesterol level was significantly lower in perilla oil-treated mice
      compared with palm oil-treated mice. HFD-induced lipid accumulation was also
      lower in thoracic aorta and liver by perilla oil compared with palm oil. Perilla
      oil also decreased hepatic triglyceride level without changing the liver weight.
      Perilla oil treatment increased the AMP-activated protein kinase and acetyl-CoA
      carboxylase phosphorylation and the lipolytic protein levels, whereas it
      decreased the lipogenic protein levels in the liver. In conclusion, perilla oil
      reduced serum cholesterol and arterial and hepatic lipid accumulation in HFD-fed
      mice. The data suggest that perilla oil improves the balance of lipogenic and
      lipolytic protein expression, and ameliorates obesity-induced metabolic disorders
      and cardiovascular diseases.

PMID- 30207815
TI  - Multidrug-resistant Klebsiella pneumoniae: challenges for treatment, prevention
      and infection control.
AB  - INTRODUCTION: Management of antimicrobial resistance in multi-drug-resistant
      Klebsiella pneumoniae (MDR-KP) is a major challenge for clinicians. The optimal
      treatment option for MDR-KP infections is still not well established. Combination
      therapies including high-dose meropenem, colistin, fosfomycin, tigecycline, and
      aminoglycosides are widely used, with suboptimal results. New antimicrobials
      targeting MDR-KP have been developed during the last decades and are now at
      various stages of clinical research. Areas covered: The PubMed database was
      searched to review the most significant literature on the topic, with a special
      consideration for articles coming from endemic countries. Expert commentary: We
      reviewed the currently available treatment options, discussing the
      characteristics of new antibiotics with activity against MDR Gram-negative
      bacteria and the strategies for preventing the spread of MDR-KP. While we wait
      for real-world data from novel compounds, coordinated strategies and common
      efforts in infection control and stewardship programs remain the cornerstone for
      limiting, or potentially reversing, conditions that favor the spread of MDR-KP.

PMID- 30207816
TI  - An evaluation of voclosporin for the treatment of lupus nephritis.
AB  - INTRODUCTION: Lupus nephritis (LN) is associated with significant morbidity and
      mortality. Current treatment outcomes remain suboptimal. No disease modifying
      medications are licensed for the treatment of LN. Voclosporin, a novel
      calcineurin inhibitor, has been investigated as induction therapy in LN in
      combination with myocophenolate mofetil (MMF) and a glucocorticoid (GC). Two
      phase II trials of voclosporin were the first trials of a potential treatment of
      active LN that met their primary endpoints. Areas covered: This article reviews
      the pharmacology of voclosporin and the efficacy and safety data from the two
      existing phase II trials. In the phase IIb randomized controlled trial AURA-LV,
      voclosporin was shown to be superior to placebo, when used in combination with
      MMF (1-2 g/day) and GC, in achieving remission in active LN. Expert opinion:
      While the positive outcome of existing trials is promising, further data
      confirming its efficacy and evaluating its safety are required. A phase III trial
      is currently recruiting. Importantly, the positive results were achieved despite
      a novel and rapid GC taper regime, suggesting that rapid taper of GC may be a
      viable treatment option in active LN which merits further investigation.

PMID- 30207817
TI  - Tokyo-1 Mutation: Hereditary Spherocytosis in a Hispanic Newborn Presenting as
      Early Onset Severe Hyperbilirubinemia.
AB  - BACKGROUND: Hereditary spherocytosis in the Hispanic population does not often
      present with severe hyperbilirubinemia. Spectrin and band 3 mutations are most
      frequent in this population. CASE REPORT: We present a Hispanic full-term female
      newborn with early onset significant hyperbilirubinemia without a history of
      familial hemolytic disorders. She was diagnosed with hereditary spherocytosis
      based on laboratory findings, including presence of spherocytes on a peripheral
      smear, and was later found by next-generation sequencing to have Tokyo-1
      mutation, an ANK1 gene mutation, that was previously only reported in Japanese
      population. CONCLUSION: Our report adds to the currently limited literature of
      the genetic spectrum and characteristics of hereditary spherocytosis in the
      Hispanic population. The absence of a positive family history does not preclude
      hereditary spherocytosis as a differential for pathologic neonatal
      hyperbilirubinemia.

PMID- 30207818
TI  - The association of environmental, meteorological, and pollen count variables with
      asthma-related emergency department visits and hospitalizations in the Bronx.
AB  - OBJECTIVE: To better understand how meteorological variables, air quality
      variables, and pollen counts collectively contribute to asthma-related emergency
      department visits (AREDV) and asthma-related hospitalizations (ARH) among
      pediatric and adult patients in the New York City borough of the Bronx. METHODS:
      The numbers of daily adult and pediatric AREDV and ARH from 2001 to 2008 were
      obtained from three Bronx hospitals. After removing outliers, interpolating
      missing data, and standardizing variable values by scaling the data using z
      scores, data were analyzed using Spearman rank tests and linear regression models
      for the full year and each season. RESULTS: There were a total of 42,065 AREDV
      and 1,664 ARH at both Bronx hospitals. With the exception of a spring peak in
      AREDVs, AREDVs and ARHs follow a cyclical pattern, climbing in the fall,
      plateauing in the winter, dropping in the spring, and reaching a low in the
      summer. Among the 11 air quality, meteorological, and pollen count variables,
      temperature and tree pollen made the greatest contribution to AREDV with scaled
      coefficients of -0.337 and 0.311 respectively; equating to an additional AREDV
      for every 5.0-unit decrease in temperature and an additional AREDV for every
      186.0-unit increase in tree pollen. These two variables were confirmed to have
      independent associations with AREDV prior to the data interpolation. Grass pollen
      was also found to have a relatively large contribution to AREDV during the summer
      with a scaled coefficient of 0.314, equating to an additional AREDV for every 2.3
      unit increase in grass pollen. CONCLUSION: There are distinct peaks of increased
      AREDVs that are closely associated with increased tree pollen counts in the
      spring and decreasing temperatures in the fall. Early anticipation of these air
      quality, meteorological, and pollen factor changes based on ongoing surveillance
      could potentially guide clinical practice and minimize AREDVs in the Bronx.

PMID- 30207819
TI  - Influence of Maternity Leave on Exclusive Breastfeeding: Analysis from Two
      Surveys Conducted in the Federal District of Brazil.
AB  - BACKGROUND: Since the 1980s, Brazil has implemented several initiatives to
      support breastfeeding. Maternity leave, paid in full for 16 weeks, has been
      available since 1988. However, few studies in Brazil have analyzed the impacts of
      maternity leave on breastfeeding using population-based indicators. Research aim:
      The aim was to analyze the association between maternity leave and exclusive
      breastfeeding interruption in children younger than 4 months residing in the
      Federal District of Brazil, in 2008 and 2014. METHODS: Data from two surveys were
      used: the 2008 Second National Survey on Prevalence of Breastfeeding and the 2014
      Monitoring of Infant Feeding Practices. The sample included 1,742 mothers with
      children younger than 4 months residing in the Federal District and using the
      Public Unified Health System. The main independent variable was the mother being
      on maternity leave and the outcome was interruption of exclusive breastfeeding.
      Multiple analyses were performed to test the association between maternity leave
      and the risk of interrupting exclusive breastfeeding, adjusting for
      socioeconomic, demographic, and biomedical characteristics. RESULTS: In 2008 and
      2014, the prevalence of exclusive breastfeeding was 60% and 71.4% and prevalence
      of maternity leave was 27% and 41%, respectively. The lack of maternity leave was
      strongly associated with interruption of exclusive breastfeeding in 2008
      (prevalence ratio [PR] = 1.78, 95% confidence interval [CI] [1.12, 2.82]) and in
      2014 (PR = 3.95, 95% CI [1.88, 8.31]) after adjusting for confounding variables.
      CONCLUSION: Not being on maternity leave was strongly associated with the
      interruption of exclusive breastfeeding among employed women residing in the
      Federal District.

PMID- 30207820
TI  - LEAARC News Brief.

PMID- 30207821
TI  - Improving efficiency of pediatric emergency asthma treatment by using metered
      dose inhaler.
AB  - OBJECTIVE: Evidence suggests using metered dose inhaler (MDI) to treat acute
      asthma in the Emergency Department reduces length of stay, though methods of
      implementation are lacking. We modified a treatment pathway to recommend use of
      MDI for mild-moderate asthma in a pediatric ED. METHODS: A baseline review
      assessed discharged patients >2 years with an asthma diagnosis and non-emergent
      Emergency Severity Index triage assessment (3/4). Our multi-disciplinary team
      developed an intervention to increase MDI use instead of continuous albuterol
      (CA) using the following: (1) Redesign the asthma pathway and order set
      recommending MDI for ESI 3/4 patients. (2) Adding a conditional order for
      Respiratory Therapists to reassess and repeat MDI until patient reached mild
      assessment. The primary outcome was the percentage discharged within 3 hours,
      with a goal of a 10% increase compared to pre-intervention. Balancing measures
      included admission and revisit rates. RESULTS: 7635 patients met eligibility
      before pathway change; 12,673 were seen in the subsequent 18 months. For target
      patients, the percentage discharged in <3 hours increased from 39% to 49%;
      reduction in median length of stay was 33 minutes. We identified special cause
      variation for reduction in CA use from 43% to 25%; Revisit rate and length of
      stay for higher-acuity patients did not change; overall asthma admissions
      decreased by 8%. Changes were sustained for 18 months. CONCLUSION: A change to an
      ED asthma pathway recommending MDI for mild-moderate asthma led to a rapid and
      sustained decrease in continuous albuterol use, length of stay, and admission
      rate.

PMID- 30207822
TI  - Are interprofessional healthcare teams meeting patient expectations? An
      exploration of the perceptions of patients and informal caregivers.
AB  - Poor teamwork skills in healthcare have been found to be a contributing cause of
      negative incidents in patient care, whilst effective teamwork has been linked to
      more positive patient outcomes. The aim of this research is to explore views of
      patients and informal caregivers on the key characteristics of effective
      healthcare teams and their experiences of healthcare teams using a qualitative
      approach. A focus group schedule was developed from existing literature to
      explore this. Topics included the purpose and value of teams in patient care, key
      attributes and their impact on patient care. Patients and informal caregivers
      were recruited via convenience sampling. Three focus groups were conducted.
      Thematic analysis identified a number of themes associated with effective teams.
      These themes included the perceived purpose of teams, perceptions about the
      structure of a team, team-based communication, the role of patients, delivery of
      care. Research participants noted the importance of key characteristics in
      effective teams, but felt that these were not always consistently present.
      Communication was considered to be the most important attribute in team working
      and also appeared to be the area in which the patient experience can be
      significantly improved. It is clear from the findings of this research that
      further improvements in teamwork skills in healthcare are needed to achieve
      effective collaborative practice, sustainable service delivery models and optimal
      patient care.

PMID- 30207823
TI  - Postpartum Depression Risk in Husbands of Women Who Had Caesarean Section
      Deliveries in Turkey.
AB  - This study was conducted to determine the risk of postpartum depression in
      husbands of women who had a caesarean section and the factors affecting this
      risk. The study sample included husbands of 298 women who gave birth for the
      first time and via caesarean in Zonguldak Maternity and Child Health Hospital in
      Turkey. Data were collected using a data collection form and the Edinburgh
      Postnatal Depression Scale. This study revealed that more than one-third of the
      fathers had a risk of postpartum depression. It also revealed that postpartum
      depression risk was high in fathers who had girl babies and whose wives had
      postpartum depression risk.

PMID- 30207824
TI  - Crunch Time: The Transformational Universal Health Coverage Agenda for Zambia.
AB  - There is a realization worldwide that health expenditure can be catastrophic,
      exacerbate inequalities between poor and rich households, and drive people into
      poverty. As such, a number of countries seek to provide universal health coverage
      (UHC) to all of their citizens in order for everyone to access quality health
      care without financial adversity. However, attaining UHC is difficult. It has
      also been recognized that there is no universal formula for attaining UHC and
      that each country must create its own. This article describes Zambia's trajectory
      to achieving UHC from the 1990s to date. The article highlights some of the past
      institutional and financing reforms, achievements made, and gaps and challenges
      that the government is determined to address through an explicit transformational
      agenda that was launched in 2011. This agenda is being pursued with renewed vigor
      given that Zambia's economy and population are growing rapidly, the time to
      transition from external support is fast approaching, and the disease profile is
      changing.

PMID- 30207825
TI  - Time's Up for Medicine? Only Time Will Tell.

PMID- 30207826
TI  - Rise of Clinical Microbial Proteogenomics: A Multiomics Approach to
      Nontuberculous Mycobacterium-The Case of Mycobacterium abscessus UC22.
AB  - Nontuberculous mycobacterial (NTM) species present a major challenge for global
      health with serious clinical manifestations ranging from pulmonary to skin
      infections. Multiomics research and its applications toward clinical microbial
      proteogenomics offer veritable potentials in this context. For example, the
      Mycobacterium abscessus, a highly pathogenic NTM, causes bronchopulmonary
      infection and chronic pulmonary disease. The rough variant of the M. abscessus
      UC22 strain is extremely virulent and causes lung upper lobe fibrocavitary
      disease. Although several whole-genome next-generation sequencing studies have
      characterized the genes in the smooth variant of M. abscessus, a reference genome
      sequence for the rough variant was generated only recently and calls for further
      clinical applications. We carried out whole-genome sequencing and proteomic
      analysis for a clinical isolate of M. abscessus UC22 strain obtained from a
      pulmonary tuberculosis patient. We identified 5506 single-nucleotide variations
      (SNVs), 63 insertions, and 76 deletions compared with the reference genome. Using
      a high-resolution LC-MS/MS-based approach (liquid chromatography tandem mass
      spectrometry), we obtained protein coding evidence for 3601 proteins,
      representing 71% of the total predicted genes in this genome. Application of
      proteogenomic approach further revealed seven novel protein-coding genes and
      enabled refinement of six computationally derived gene models. We also identified
      30 variant peptides corresponding to 16 SNVs known to be associated with drug
      resistance. These new observations offer promise for clinical applications of
      microbial proteogenomics and next-generation sequencing, and provide a resource
      for future global health applications for NTM species.

PMID- 30207827
TI  - Geometric partitioning of cohesin and condensin is a consequence of chromatin
      loops.
AB  - SMC (structural maintenance of chromosomes) complexes condensin and cohesin are
      crucial for proper chromosome organization. Condensin has been reported to be a
      mechanochemical motor capable of forming chromatin loops, while cohesin passively
      diffuses along chromatin to tether sister chromatids. In budding yeast, the
      pericentric region is enriched in both condensin and cohesin. As in higher
      eukaryotic chromosomes, condensin is localized to the axial chromatin of the
      pericentric region, while cohesin is enriched in the radial chromatin. Thus, the
      pericentric region serves as an ideal model for deducing the role of SMC
      complexes in chromosome organization. We find condensin-mediated chromatin loops
      establish a robust chromatin organization, while cohesin limits the area that
      chromatin loops can explore. Upon biorientation, extensional force from the
      mitotic spindle aggregates condensin-bound chromatin from its equilibrium
      position to the axial core of pericentric chromatin, resulting in amplified axial
      tension. The axial localization of condensin depends on condensin's ability to
      bind to chromatin to form loops, while the radial localization of cohesin depends
      on cohesin's ability to diffuse along chromatin. The different chromatin
      tethering modalities of condensin and cohesin result in their geometric
      partitioning in the presence of an extensional force on chromatin.

PMID- 30207828
TI  - Layers of regulation of cell-cycle gene expression in the budding yeast
      Saccharomyces cerevisiae.
AB  - In the budding yeast Saccharomyces cerevisiae, transcription factors (TFs)
      regulate the periodic expression of many genes during the cell cycle, including
      gene products required for progression through cell-cycle events. Experimental
      evidence coupled with quantitative models suggests that a network of
      interconnected TFs is capable of regulating periodic genes over the cell cycle.
      Importantly, these dynamical models were built on transcriptomics data and
      assumed that TF protein levels and activity are directly correlated with mRNA
      abundance. To ask whether TF transcripts match protein expression levels as cells
      progress through the cell cycle, we applied a multiplexed targeted mass
      spectrometry approach (parallel reaction monitoring) to synchronized populations
      of cells. We found that protein expression of many TFs and cell-cycle regulators
      closely followed their respective mRNA transcript dynamics in cycling wild-type
      cells. Discordant mRNA/protein expression dynamics was also observed for a subset
      of cell-cycle TFs and for proteins targeted for degradation by E3 ubiquitin
      ligase complexes such as SCF (Skp1/Cul1/F-box) and APC/C (anaphase-promoting
      complex/cyclosome). We further profiled mutant cells lacking B-type cyclin/CDK
      activity ( clb1-6) where oscillations in ubiquitin ligase activity, cyclin/CDKs,
      and cell-cycle progression are halted. We found that a number of proteins were no
      longer periodically degraded in clb1-6 mutants compared with wild type,
      highlighting the importance of posttranscriptional regulation. Finally, the TF
      complexes responsible for activating G1/S transcription (SBF and MBF) were more
      constitutively expressed at the protein level than at periodic mRNA expression
      levels in both wild-type and mutant cells. This comprehensive investigation of
      cell-cycle regulators reveals that multiple layers of regulation (transcription,
      protein stability, and proteasome targeting) affect protein expression dynamics
      during the cell cycle.

PMID- 30207831
TI  - Ending Sexual Harassment in Academic Medicine.

PMID- 30207829
TI  - Tracking yeast pheromone receptor Ste2 endocytosis using fluorogen-activating
      protein tagging.
AB  - To observe internalization of the yeast pheromone receptor Ste2 by fluorescence
      microscopy in live cells in real time, we visualized only those molecules present
      at the cell surface at the time of agonist engagement (rather than the total
      cellular pool) by tagging this receptor at its N-terminus with an exocellular
      fluorogen-activating protein (FAP). A FAP is a single-chain antibody engineered
      to bind tightly a nonfluorescent, cell-impermeable dye (fluorogen), thereby
      generating a fluorescent complex. The utility of FAP tagging to study trafficking
      of integral membrane proteins in yeast, which possesses a cell wall, had not been
      examined previously. A diverse set of signal peptides and propeptide sequences
      were explored to maximize expression. Maintenance of the optimal FAP-Ste2 chimera
      intact required deletion of two, paralogous, glycosylphosphatidylinositol (GPI)
      anchored extracellular aspartyl proteases (Yps1 and Mkc7). FAP-Ste2 exhibited a
      much brighter and distinct plasma membrane signal than Ste2-GFP or Ste2-mCherry
      yet behaved quite similarly. Using FAP-Ste2, new information was obtained about
      the mechanism of its internalization, including novel insights about the roles of
      the cargo-selective endocytic adaptors Ldb19/Art1, Rod1/Art4, and Rog3/Art7.

PMID- 30207830
TI  - A balance of deubiquitinating enzymes controls cell cycle entry.
AB  - Protein degradation during the cell cycle is controlled by the opposing
      activities of ubiquitin ligases and deubiquitinating enzymes (DUBs). Although the
      functions of ubiquitin ligases in the cell cycle have been studied extensively,
      the roles of DUBs in this process are less well understood. Here, we used an
      overexpression screen to examine the specificities of each of the 21 DUBs in
      budding yeast for 37 cell cycle-regulated proteins. We find that DUBs up-regulate
      specific subsets of proteins, with five DUBs regulating the greatest number of
      targets. Overexpression of Ubp10 had the largest effect, stabilizing 15 targets
      and delaying cells in mitosis. Importantly, UBP10 deletion decreased the
      stability of the cell cycle regulator Dbf4, delayed the G1/S transition, and
      slowed proliferation. Remarkably, deletion of UBP10 together with deletion of
      four additional DUBs restored proliferation to near-wild-type levels. Among this
      group, deletion of the proteasome-associated DUB Ubp6 alone reversed the G1/S
      delay and restored the stability of Ubp10 targets in ubp10Delta cells. Similarly,
      deletion of UBP14, another DUB that promotes proteasomal activity, rescued the
      proliferation defect in ubp10Delta cells. Our results suggest that DUBs function
      through a complex genetic network in which their activities are coordinated to
      facilitate accurate cell cycle progression.

PMID- 30207832
TI  - Impact of Immigrant Status on Aggressive Medical Care Counter to Patients' Values
      Near Death among Advanced Cancer Patients.
AB  - BACKGROUND: Little is known about disparities in end-of-life (EoL) care between
      U.S. immigrants and nonimmigrants. OBJECTIVE: To determine immigrant/nonimmigrant
      advanced cancer patient differences in receipt of values-inconsistent aggressive
      medical care near the EoL. DESIGN: Analysis of data from Coping with Cancer, a
      federally funded, prospective, multi-institutional cohort study of advanced
      cancer patients with limited life expectancies recruited from 2002 to 2008.
      SETTING/SUBJECTS: U.S. academic medical center and community-based clinics. Self
      reported immigrant (n = 41) and nonimmigrant (n = 261) advanced cancer patients
      with poor prognoses who died within the study observation period. MEASUREMENTS:
      The primary independent/predictor variable was patient immigrant status. Primary
      outcome variables: (1) aggressive medical care near death, operationalized as the
      use of mechanical ventilation, resuscitation, feeding tube, and/or antibiotics in
      the last week of life and (2) receipt of values inconsistent aggressive care,
      operationalized as receiving aggressive care inconsistent with stated preferences
      for comfort-focused EoL care. RESULTS: In a propensity-weighted sample (N = 302),
      in which immigrant and nonimmigrant groups were weighted to be demographically
      similar, immigrants were significantly more likely than nonimmigrants to receive
      aggressive medical care [OR 1.9; 95% CI (1.0-3.6); p = 0.042] and values
      inconsistent aggressive medical care [OR 2.1; 95% CI (1.1-4.2); p = 0.032] near
      death. CONCLUSIONS: Immigrant, as compared with nonimmigrant, advanced cancer
      patients are not only more likely to receive aggressive EoL care, but also more
      likely to receive care counter to their wishes. These findings indicate potential
      disparities in, rather than differences in preference for, aggressive care and a
      need for further investigation into potential causes of these disparities.

PMID- 30207834
TI  - TLK2 enhances aggressive phenotypes of glioblastoma cells through the activation
      of SRC signaling pathway.
AB  - Glioblastoma are among the most common forms of cancer affecting the central
      nervous system, and yet there is currently no effective means of treating them.
      In the current study, we reported that tousled-like kinase 2 (TLK2) is a key
      factor in glioblastoma that modulates SRC signaling, thereby driving tumor
      malignancy. TLK2 is commonly upregulated in glioblastoma, and such upregulation
      was associated with poor patient outcomes. TLK2 overexpression induced cell
      growth, migration, invasion, and epithelial-mesenchymal transition, and cell
      cycle arrest, while TLK2 knockdown had the opposite effect. SRC pathway
      inhibition by Saracatinib resulted in reduced TLK2-mediated glioblastoma
      migration, invasion, confirming a key role for SRC signaling in regulating the
      functions of TLK2. Together, our findings demonstrate that glioblastoma TLK2
      overexpression acts as a key driver of tumor malignancy via SRC signaling
      pathway.

PMID- 30207835
TI  - Circular RNA ciRS-7 triggers the migration and invasion of esophageal squamous
      cell carcinoma via miR-7/KLF4 and NF-kappaB signals.
AB  - Esophageal squamous cell carcinoma (ESCC) is one of the most prevalent and deadly
      cancers worldwide, especially in Eastern Asia. It has been indicated that
      circular RNAs (circRNA) are the key regulators in the development and progression
      of human cancers. We therefore evaluated the expression and regulation effects of
      ciRS-7 on the progression of ESCC, which is a recently identified circRNA and
      acts as a natural competing endogenous RNA. The expression of ciRS-7 was
      significantly increased in the ESCC tissues and cells as compared with their
      corresponding controls. In vitro study showed that ciRS-7 can promote the
      migration and invasion of ESCC cells. Over expression of miR-7, one of well-known
      targets of ciRS-7, can attenuate ciRS-7 induced invasion of ESCC cells and over
      expression of matrix metalloproteinase 2 (MMP2). The expression of stem cell
      marker Kruppel-like factor-4 (KLF-4), which has been reported as the target of
      miR7, increased significantly in ciRS-7 transfected ESCC cells. Knockdown of KLF
      4 also attenuated over expression of ciRS-7 induced cell invasion. In addition,
      BAY 11-7082, the inhibitor of NF-kappaB, partially reversed ciRS-7 induced cell
      invasion. Mechanically studies indicated that ciRS-7 increased the expression of
      p65 via increasing the phosphorylation of IKK-alpha. Collectively, our present
      study revealed that ciRS-7 can trigger the migration and invasion of ESCC cells
      via miR-7/KLF4 and NF-kappaB signals. Targeted inhibition of ciRS-7 might be a
      potential approach for ESCC treatment.

PMID- 30207833
TI  - Inferring Whether Officials Are Corruptible From Looking at Their Faces.
AB  - While inferences of traits from unfamiliar faces prominently reveal stereotypes,
      some facial inferences also correlate with real-world outcomes. We investigated
      whether facial inferences are associated with an important real-world outcome
      closely linked to the face bearer's behavior: political corruption. In four
      preregistered studies ( N = 325), participants made trait judgments of unfamiliar
      government officials on the basis of their photos. Relative to peers with clean
      records, federal and state officials convicted of political corruption (Study 1)
      and local officials who violated campaign finance laws (Study 2) were perceived
      as more corruptible, dishonest, selfish, and aggressive but similarly competent,
      ambitious, and masculine (Study 3). Mediation analyses and experiments in which
      the photos were digitally manipulated showed that participants' judgments of how
      corruptible an official looked were causally influenced by the face width of the
      stimuli (Study 4). The findings shed new light on the complex causal mechanisms
      linking facial appearances with social behavior.

PMID- 30207836
TI  - A Simplified Method for Three-Dimensional Optical Imaging and Measurement of
      Patients with Chest Wall Deformities.
AB  - BACKGROUND: Pectus excavatum and carinatum are two of the most commonly observed
      chest wall deformities in pediatrics. The standard diagnostic evaluation for
      these conditions includes either chest radiograph (CXR) or computed tomography
      (CT). Our research aims to develop a novel and reliable way of quantifying chest
      wall deformities in the clinic setting without radiation exposure. METHODS: Using
      a handheld structured light scanner, we created three-dimensional (3D) models of
      patients with chest wall deformities through an IRB-approved protocol. Raters
      from a variety of backgrounds were then asked to take measurements based on the
      3D model utilizing commercially available 3D graphical software. The standard
      deviation of the measurements and intraclass correlation coefficient (ICC) were
      then calculated to quantify inter-rater reliability. RESULTS: Sixty patients with
      pectus excavatum (Haller index range 2.0-6.38) and pectus carinatum were enrolled
      and imaged in our outpatient clinic using a structured light scanner. Five
      patients were used to verify interuser reliability. The standard deviation of all
      the measurements was 2.2 mm. The ICC for absolute agreement was 0.99139, with 1.0
      being perfect correlation. CONCLUSION: Structured light scanners provide an
      alternative approach to quantifying chest wall deformities in pediatric patients
      without radiation exposure. Our method is highly reliable, even among users with
      minimal image processing or 3D modeling experience. Our protocol can potentially
      be used to track treatment progress in children with chest wall deformities.

PMID- 30207837
TI  - Force localization modes in dynamic epithelial colonies.
AB  - Collective cell behaviors, including tissue remodeling, morphogenesis, and cancer
      metastasis, rely on dynamics among cells, their neighbors, and the extracellular
      matrix. The lack of quantitative models precludes understanding of how cell-cell
      and cell-matrix interactions regulate tissue-scale force transmission to guide
      morphogenic processes. We integrate biophysical measurements on model epithelial
      tissues and computational modeling to explore how cell-level dynamics alter
      mechanical stress organization at multicellular scales. We show that traction
      stress distribution in epithelial colonies can vary widely for identical
      geometries. For colonies with peripheral localization of traction stresses, we
      recapitulate previously described mechanical behavior of cohesive tissues with a
      continuum model. By contrast, highly motile cells within colonies produce
      traction stresses that fluctuate in space and time. To predict the traction force
      dynamics, we introduce an active adherent vertex model (AAVM) for epithelial
      monolayers. AAVM predicts that increased cellular motility and reduced
      intercellular mechanical coupling localize traction stresses in the colony
      interior, in agreement with our experimental data. Furthermore, the model
      captures a wide spectrum of localized stress production modes that arise from
      individual cell activities including cell division, rotation, and polarized
      migration. This approach provides a robust quantitative framework to study how
      cell-scale dynamics influence force transmission in epithelial tissues.

PMID- 30207838
TI  - The rumen microbiome: a crucial consideration when optimising milk and meat
      production and nitrogen utilisation efficiency.
AB  - Methane is generated in the foregut of all ruminant animals by the microorganisms
      present. Dietary manipulation is regarded as the most effective and most
      convenient way to reduce methane emissions (and in turn energy loss in the
      animal) and increase nitrogen utilization efficiency. This review examines the
      impact of diet on bovine rumen function and outlines what is known about the
      rumen microbiome. Our understanding of this area has increased significantly in
      recent years due to the application of omics technologies to determine microbial
      composition and functionality patterns in the rumen. This information can be
      combined with data on nutrition, rumen physiology, nitrogen excretion and/or
      methane emission to provide comprehensive insights into the relationship between
      rumen microbial activity, nitrogen utilisation efficiency and methane emission,
      with an ultimate view to the development of new and improved intervention
      strategies.

PMID- 30207839
TI  - Skeletal muscle regeneration by extracellular matrix biological scaffold: a case
      report.
AB  - A case report of a 17-year-old female with a complex, non-healing, two-month-old
      wound, wherein exposed fibula was evident. On assessment, the wound measured 35cm
      in length, 3cm in width, and was 1cm deep, along the lateral aspect of the left
      lower leg. A rim of granulation tissue was visible along the wound edge. The
      exposed bone measured 20cm in length, and was 3cm wide. Porcine-derived,
      extracellular matrix (ECM) biological scaffold was placed on the wound bed to
      facilitate regeneration of the patient's skeletal muscle. The patient healed
      without incident postoperatively and was able to regain her ambulatory ability.
      This technique has, in the authors' experience, proved successful and without
      complication in complex non-healing wound cases, particularly in patients who
      have lost a large volume of skeletal muscle. The authors believe that patients
      and surgeons would benefit from early consideration of ECM biological scaffolds
      in similar types of large, open, and complex wounds.

PMID- 30207840
TI  - Use of local intrinsic muscle flaps for diabetic foot and ankle reconstruction: a
      systematic review.
AB  - OBJECTIVE: To assess the outcomes of local intrinsic muscle flaps specifically in
      the surgical reconstruction of foot and ankle wounds in patients with diabetes.
      METHOD: A systematic review of the literature was conducted by three independent
      reviewers using several databases and search engines. The following search terms
      were used: foot, ankle, diabetes mellitus, peripheral neuropathy, Charcot
      neuroarthropathy, ulceration, wound, muscle, flap, surgical offloading, diabetic
      reconstruction, local intrinsic, abductor digiti minimi, abductor hallucis,
      extensor digitorum brevis, flexor digitorum brevis, flexor digiti minimi. Studies
      meeting the following criteria were included: English language studies, studies
      published from 1997 to 2017 (inclusive of the last 20 years), patients with
      diabetes treated for foot and/or ankle wounds, use of local intrinsic muscle
      flaps, follow-up period of six months or more postoperatively, documentation of
      healing rates, complications, and need for revisional surgery. Studies that were
      entirely literature reviews, descriptions of only surgical technique and/or
      cadaveric studies and patients without diabetes were excluded. RESULTS: A total
      of 13 selected studies met the above inclusion criteria and were used for data
      extraction from a total of 113 patients in which 92 local intrinsic muscle flaps
      were performed for diabetic foot and/or ankle reconstruction, of which 80 (87%)
      muscle flaps demonstrated success, while 12 (13%) flaps encountered
      complications. CONCLUSION: Although local intrinsic muscle flaps demonstrated a
      relatively high success rate when used for the definitive closure of certain
      diabetic foot and ankle wounds based on existing evidence, our systematic review
      emphasises the need for more high-quality, larger comparative studies to
      investigate their efficacy and failure rates in diabetic foot and/or ankle
      reconstruction.

PMID- 30207841
TI  - French Canadian translation and the validity and inter-rater reliability of the
      ISTAP Skin Tear Classification System.
AB  - OBJECTIVE: To adapt the International Skin Tear Advisory Panel (ISTAP) skin tear
      classification system into French Canadian, and to test the content validity and
      inter-rater reliability of the translated version. METHOD: Phase one included the
      translation of the ISTAP skin tear classification system into French Canadian,
      using a forward-back translation method. Following this the translated version
      was tested for content validity and inter-rater reliability with registered
      nurses from a French acute care hospital in Ottawa, Canada. RESULTS: The French
      Canadian translation of the ISTAP skin tear classification system was evaluated
      by 92 nurses without in-depth wound care training. The adapted version obtained a
      substantial level of agreement between users, (Fleiss' Kappa = 0.69). CONCLUSION:
      The study tested the content validity and inter-rater reliability of the French
      Canadian version of the ISTAP skin tear classification system. The results
      support previous studies and further validate the classification system as a
      reliable method for classifying skin tears. The study supports ISTAP's goal of
      establishing a global language for describing and documenting skin tears.

PMID- 30207842
TI  - Wound Healer to the rescue.

PMID- 30207843
TI  - Medical applications of cold atmospheric plasma: state of the science.
AB  - Cold atmospheric plasmas (CAP) have been used in multiple medical fields and have
      become a promising medical technology. CAP-generating devices are safe and easy
      to operate and can now be manufactured at a low cost due to advancements in
      electronics and microchips. A primary application of CAP is as a broad-spectrum
      antimicrobial technology. With the high incidence of infections caused by drug
      resistant microorganisms, a non-antibiotic based treatment modality such as CAP
      holds great therapeutic promise, particularly in the wound care field. In
      addition to its antimicrobial properties, CAP treatment enhances wound healing by
      increasing cutaneous microcirculation, monocyte stimulation, and keratinocyte
      proliferation. CAP has been used by dentists for disinfection of teeth, enhancing
      gingival fibroblast activity, and even teeth whitening. CAP can combat tumour
      growth by increasing the efficacy of antitumour therapeutic agents, reactivating
      apoptotic pathways, or down-regulating growth-related gene sites. Most of the
      health-care related research on CAP has occurred in the past 15 years; the field
      is relatively young and needs additional research, as well as confirmation of the
      existing supporting literature. The purpose of this report is to provide the
      reader with an overview of the therapeutic application of the cold plasma
      technology.

PMID- 30207845
TI  - Bond and heal: from Asia with love.

PMID- 30207844
TI  - Continuous diffusion of oxygen improves diabetic foot ulcer healing when compared
      with a placebo control: a randomised, double-blind, multicentre study.
AB  - OBJECTIVE: The aim of this study was to assess whether continuous diffusion of
      oxygen improves healing in people receiving treatment for diabetic foot ulcers
      (DFU). METHOD: A double-blind, placebo control randomised study to receive either
      active continuous diffusion of oxygen (CDO) therapy using an active CDO device,
      or a fully operational placebo device without delivering oxygen. Patients were
      followed until closure or 12 weeks. Patients, caretakers, treating physicians and
      independent evaluators were blinded to the study arm. All patients received
      identical offloading, debridement, dressings and follow-up. RESULTS: We enrolled
      146 people with DFUs (77% male, aged 56.3+/-12.4 years). A significantly higher
      proportion (195%) of DFUs healed in the CDO arm compared with placebo (32.4%
      versus 16.7%, p=0.033). The time to 50% DFU closure was significantly shorter in
      patients that received CDO therapy (mean 18.4 versus 28.9 days, p=0.001). There
      were no differences in overall adverse events (p=0.66) or ulcer-related adverse
      events (p=0.30) in the active and placebo treatment groups. The relative
      performance of active CDO over placebo became greater when used in larger wounds
      (273%), in more chronic wounds (334%) and in weight bearing wounds (465%).
      CONCLUSION: The results of this study demonstrate that CDO leads to higher
      proportion of healed DFUs (p=0.033) and a faster time to closure compared with
      placebo in people with DFUs (p=0.015). Relative performance did not vary
      significantly with wound size (p=0.80), but revealed better relative performance
      in more chronic wounds (p=0.008) and in weight-bearing wounds (p=0.003).

PMID- 30207846
TI  - Reconstruction of infected trunk wounds with pedicled rectus abdominis
      musculocutaneous flaps: a retrospective case series.
AB  - OBJECTIVE: To completely treat and cover extensively infected trunk defects,
      reconstruction should be performed using a sufficiently vascularised flap, such
      as a muscle or musculocutaneous flap after perfect debridement. These
      reconstructive surgeries are challenging in patients with severe comorbidities.
      In this case series, we describe extensively infected trunk defect
      reconstruction, in patients with severe comorbidities, using a pedicled rectus
      abdominis musculocutaneous flap and suggest an algorithm for reconstruction.
      METHOD: Between March 2011 and March 2015, participating patients underwent
      reconstruction of extensively infected trunk defects using a pedicled rectus
      abdominis musculocutaneous flap. All patients had diabetes and hypertension, and
      several patients had severe comorbidities, including heart and renal failure.
      Bacterial cultures revealed that meticillin-resistant Staphylococcus aureus
      (MRSA) was present in seven patients (with concurrent Pseudomonas aeruginosa in
      two patients), multidrug-resistant Acinetobacter baumannii in one patient and
      Mycobacterium tuberculosis in two patients. RESULTS: A total of 10 patients
      underwent the procedure. The pedicled rectus abdominis musculocutaneous flaps
      survived completely in all 10 patients. There were no complications related to
      the flaps, although two patients developed minor wound dehiscence, which may be
      due to their comorbidities. There were no signs of recurrent infection during the
      follow-up period in each case. CONCLUSION: Reconstruction using the pedicled
      rectus abdominis musculocutaneous flap is a good treatment option for extensively
      infected three-dimensional trunk defects, even for patients with severe
      comorbidities.

PMID- 30207847
TI  - Knee reconstruction using a distally based anterolateral thigh flap: an
      anatomical cadaveric study.
AB  - OBJECTIVE: To study the vascular territory of the descending branch of the
      lateral circumflex femoral artery and its anastomosis around the knee and to
      identify the cutaneous perforator supply to the distally-based or reverse flow
      anterolateral thigh (dbALT) flap. In particular, the distance of the first
      perforator branch arising from the knee and above region, as well as the number
      of branches and position of each perforator, beneficial for effective flap
      design, are also examined. METHOD: Fresh cadaveric lower limbs were dissected and
      the distance of the first perforator branch arising from the knee and above
      regions, which are vascular supplies for flaps, as well as the number of branches
      and position of each perforator are described. RESULTS: A total of 54 thigh
      cadavers had at least two cutaneous perforator branches above the knee 10cm from
      the superior border of the lateral patella. The mean (+/- standard deviation) of
      the first perforator distance was 2.57+/-0.93cm above the superior-lateral border
      of the patella. All perforating branches were 4+/-2cm, 93% were 10+/-2cm from the
      superior lateral border of patella, and 100% were at 20+/-3cm (mid-thigh length)
      which were the traditional anterolateral thigh flap. CONCLUSION: The dbALT flap
      technique resulted in constant and reliable references about perforator sites.
      Thus, this type of flap is a viable option in patients who present with soft
      tissue defects around the knee and upper third of the leg.

PMID- 30207849
TI  - Increasing productivity with smartphone digital imagery wound measurements and
      analysis.
AB  - OBJECTIVE: The primary aim was to determine the productivity increase using
      digital imagery for better documentation and analysis. A case series was done in
      a specialised care centre with patients managed with advanced dressings and using
      state-of-the-art smartphone technology for documentation to save costs and time.
      METHOD: Wounds were cleansed and debrided before using the application to
      photograph, document, measure and analyse the wounds. The smartphone app was
      oriented parallel to the plane of the wound, where possible, to obtain accurate
      measurements. A longitudinal study report was generated for each wound and showed
      the progress of the wound healing until the wound was closed. RESULTS: A sample
      size of 60 patients consisting of wounds from different locations, and a total of
      203 measurements and analyses were conducted over a period of seven months. The
      wound monitoring app proved to be effective for wound monitoring and required
      less than two hours' training. A report summary of wounds recorded could also be
      generated automatically through the dashboard. All 60 patients' cases were
      automatically recorded, measured and presented into reports for use in clinical
      analysis. There was a significant time savings (27 hours per day for a
      specialised care centre with 10 nurses) increase over manual wound documentation
      and measuring methods. CONCLUSION: The app provided a non-contact, easy to use,
      reliable and accurate smart wound management solution for clinicians and
      physicians to track wound healing in patients. The app could also be used by
      patients and caregivers for home monitoring of their wounds.

PMID- 30207848
TI  - Venous leg ulcers managed using polyurethane foam with a micropore dressing: two
      case reports.
AB  - BACKGROUND: Cases of venous leg ulcers (VLU) are expected to rise due to the
      rapidly ageing population in Malaysia. Central to the management of these wounds
      is compression therapy together with an appropriate wound dressing. Pain and
      discomfort during dressing changes are common in these patients. Polyurethane
      foam dressings with SMARTPORE technology (micropore dressing; Mundipharma)
      facilitate vertical absorption of exudate to reduce risks of wound and periwound
      area maceration. They support easy dressing removal with less pain and trauma to
      the wound bed. Thus, the micropore dressing was chosen as a viable treatment
      option in these cases. CASES: Case 1, a 74-year-old diabetic female was treated
      for bilateral VLUs with micropore dressing for several months, which she noted to
      be painless and convenient. Case 2, a 49-year-old housewife with a solitary VLU
      was treated with micropore dressing, leading to good treatment results and high
      satisfaction. CONCLUSION: VLUs managed by the micropore dressing resulted in
      reduced pain and ease of use during dressing changes, as well as noticeable
      reduction in wound and periwound area maceration. The use of this type of
      dressing in these cases shows encouraging results and provides a desirable
      management option. More robust clinical studies are necessary to establish this.

PMID- 30207850
TI  - Nano-colloidal silver and chitosan bioactive wound dressings in managing diabetic
      foot ulcers: case series.
AB  - OBJECTIVE: To study the effectiveness of nano-colloidal silver and chitosan
      bioactive wound dressings in the treatment of diabetic foot ulcers (DFU). METHOD:
      Patients with DFUs were selected randomly. Wound size, appearance and presence of
      infection were recorded at each dressing change. RESULTS: We assessed five
      patients in this case series. The use of both nano-colloidal silver and chitosan
      biopolymer dressings aided wound healing. The patients did not require surgical
      debridement or amputation. All five cases in this study had a slow healing rate
      at presentation. CONCLUSION: Applications of nano-colloidal silver in conjunction
      with chitosan bioactive as primary dressings in managing DFUs cases are safe and
      help increase wound healing rates, thus, leading to significant cost savings in
      the hospital setting.

PMID- 30207851
TI  - Managing necrotising fasciitis to reduce mortality and increase limb salvage.
AB  - OBJECTIVE: Necrotising fasciitis is a rare soft-tissue infection with a high
      mortality rate. In this paper we describe our management protocol for necrotising
      fasciitis, focused on surgical approaches, which increased patients' survival
      rate. METHOD: Between March 2009 and December 2014, patients suspected of having
      necrotising fasciitis (based on laboratory and MRI examinations), underwent
      management for the infection. A patient suspected of having necrotising fasciitis
      had surgical exploration performed within eight hours. Patients underwent serial
      debridement every 24-72 hours until infection had been fully eradicated, after
      which reconstructive surgery was considered. RESULTS: A total of 34 patients
      underwent management for necrotising fasciitis, 31 of which had the infection
      confirmed. From this group, the 18 patients who underwent free flap
      reconstructive surgery were included in the study, nine of which were female with
      a mean age of 54.3 (range: 28-77) years. The patients underwent 2-5 repeat
      debridements (mean: 3.5). Reconstructive procedures were latissimus dorsi (LD)
      myocutaneous flap in 11 patients, and latissimus dorsi chimeric flap in six
      patients; the remaining patient received an latissimus dorsi myocutaneous flap,
      an latissimus dorsi perforator flap and an anterolateral thigh flap
      simultaneously. Patients were discharged from hospital and returned to daily life
      three weeks after the final procedure. The mean length of follow-up was 34.8
      months (range: 12-60 months). All 18 patients survived. CONCLUSION: With
      multidisciplinary management, the challenge of necrotising fasciitis can be
      overcome without risk of mortality risk.

PMID- 30207853
TI  - Use of Patient-Reported Outcome Measures in Quality Oncology Practice Initiative
      Registered Practices: Results of a National Survey.
AB  - PURPOSE:: Measuring patient-reported outcomes (PROs) in clinical practice has
      been associated with improved survival and quality of life for patients with
      cancer. However, this application of PROs is relatively new, and little is known
      about how practices collect PROs, which PROs are measured, and what challenges
      are met in implementation. METHODS:: We surveyed Quality Oncology Practice
      Initiative-registered practices in December 2015 to understand the current state
      of PROs use and identify areas where implementation support may be needed. PRO
      collectors were asked to describe their views, practices, and challenges with
      implementation; noncollectors were asked about their interest in and perceived
      barriers to collection. RESULTS:: Eighty-nine practices (38% of those that viewed
      the participation request) completed >= 50% of the survey and comprised the
      analytic sample. Most (79%) responders noted that collecting PROs was a high
      priority; slightly fewer actually collected PROs (69%). Most collectors (79%)
      were affiliated with hospitals or medical centers, and nearly all (94%) had
      electronic health records (EHRs). Collectors saw more patients per week than
      noncollectors ( P < .01). The PROs used by collectors addressed several topics,
      including patient distress (78%), symptoms (76%), and experience or satisfaction
      (70%). Perceived implementation challenges were similar for collectors and
      noncollectors: patient unwillingness to complete questionnaires and insufficient
      staff support; noncollectors additionally cited lack of PRO integration in the
      electronic health records. CONCLUSION:: Widespread agreement that PRO collection
      is important has led to early adoption among a sizable minority of Quality
      Oncology Practice Initiative practices. Reaching consensus regarding which PROs
      are meaningful and developing and sharing best-practices that overcome
      implementation barriers could facilitate implementation and maximize PRO utility.

PMID- 30207852
TI  - Comorbidity Assessment in the National Cancer Database for Patients With
      Surgically Resected Breast, Colorectal, or Lung Cancer (AFT-01, -02, -03).
AB  - PURPOSE:: Accurate comorbidity measurement is critical for cancer research. We
      evaluated comorbidity assessment in the National Cancer Database (NCDB), which
      uses a code-based Charlson-Deyo Comorbidity Index (CCI), and compared its
      prognostic performance with a chart-based CCI and individual comorbidities in a
      national sample of patients with breast, colorectal, or lung cancer. PATIENTS AND
      METHODS:: Through an NCDB Special Study, cancer registrars re-abstracted
      perioperative comorbidities for 11,243 patients with stage II to III breast
      cancer, 10,880 with stage I to III colorectal cancer, and 9,640 with stage I to
      III lung cancer treated with definitive surgical resection in 2006-2007. For each
      cancer type, we compared the prognostic performance of the NCDB code-based CCI
      (categorical: 0 or missing data, 1, 2+), Special Study chart-based CCI
      (continuous), and 18 individual comorbidities in three separate Cox proportional
      hazards models for postoperative 5-year overall survival. RESULTS:: Comorbidity
      was highest among patients with lung cancer (13.2% NCDB CCI 2+) and lowest among
      patients with breast cancer (2.8% NCDB CCI 2+). Agreement between the NCDB and
      Special Study CCI was highest for breast cancer (rank correlation, 0.50) and
      lowest for lung cancer (rank correlation, 0.40). The NCDB CCI underestimated
      comorbidity for 19.1%, 29.3%, and 36.2% of patients with breast, colorectal, and
      lung cancer, respectively. Within each cancer type, the prognostic performance of
      the NCDB CCI, Special Study CCI, and individual comorbidities to predict
      postoperative 5-year overall survival was similar. CONCLUSION:: The NCDB
      underestimated comorbidity in patients with surgically resected breast,
      colorectal, or lung cancer, partly because the NCDB codes missing data as CCI 0.
      However, despite underestimation of comorbidity, the NCDB CCI was similar to the
      more complete measures of comorbidity in the Special Study in predicting overall
      survival.

PMID- 30207854
TI  - Times to Diagnosis and Treatment of Lung Cancer in New South Wales, Australia: A
      Multicenter, Medicare Data Linkage Study.
AB  - INTRODUCTION:: Earlier access to lung cancer specialist (LCS) care improves
      survival. We examined times to diagnosis and treatment of patients with lung
      cancer in rural and metropolitan New South Wales (NSW) Australia, benchmarked
      against recent timeframe recommendations. MATERIALS AND METHODS:: Semistructured
      interviews of recently diagnosed patients with lung cancer from five NSW cancer
      centers were used to determine standardized time intervals to diagnosis and
      treatment, triangulated with Medicare data linkage and medical records. We used
      descriptive statistics to evaluate the primary end points of median time
      intervals from general practitioner (GP) referral to first LCS visit (GP-LCS
      interval) and to treatment start (Secondary Care interval). Univariable and
      multivariable analyses were used to study associations with delays in end points.
      Post hoc survival analyses were performed. RESULTS:: Data linkage was performed
      for 125 patients (68% stage IV; 69% metropolitan), with 108 interviewed. The
      median GP-LCS interval was 4 days, with 83% of patients seeing an LCS within the
      recommended 14 days. The median Secondary Care interval was 42 days (52% within
      42 days). There were no significant differences between time intervals faced by
      rural and metropolitan patients overall, although metropolitan patients took 18
      days less than rural counterparts to commence radiation/chemoradiation (95% CI, 
      33.2 to -2.54; P = .02). One third of patients perceived delays. Delays did not
      affect survival. CONCLUSION:: Rural and metropolitan NSW patients face comparable
      time lines to diagnosis and treatment of lung cancer. Most patients are seen by
      an LCS within recommended timeframes, but transition through Secondary Care and
      addressing patient expectations could be improved.

PMID- 30207855
TI  - Clinical Challenges and Opportunities With Current Electronic Health Records:
      Practicing Oncologists' Perspective.

PMID- 30207856
TI  - Predictors of Failed Transcystic Laparoscopic Common Bile Duct Exploration:
      Analysis of Multicenter Integrated Health System Database.
AB  - BACKGROUND: The aim of this study is to report our experience with laparoscopic
      common bile duct exploration (LCBDE) and validate the experts' opinion about
      anatomical predictors of failed transcystic LCBDE (TLCBDE) approach. METHODS:
      Patients undergoing LCBDE at Kaiser Permanente Southern California hospitals
      (2005-2015) were included. Predictors of failed TLCBDE were identified using
      bivariate analysis. RESULTS: Of 115 LCBDE, 89.6% were TLCBDE and 10.4% through
      choledochotomy. Success rate, morbidity, and length of hospital stay were 83.5%,
      6.1%, and 3.8 days respectively. Only stone size:cystic duct ratio >1 (35% versus
      63%, P = .044) was associated with failure of TLCBDE. In accordance with experts'
      opinion, there was a suggestive association of stone size >=6 mm, cystic duct <=4
      mm, multiple stones, and proximal stone location with failure; however, these did
      not reach statistical significance. CONCLUSION: LCBDE is an effective and safe
      mean of clearing common bile duct stones at community hospitals of an integrated
      health system. Previously cited contraindications for TLCBDE are not absolute,
      but rather predictors of failure.

PMID- 30207857
TI  - Experience-related reductions of myelin and axon diameter in adulthood.
AB  - The production of new myelin has been highlighted as an underappreciated
      mechanism of brain plasticity, but whether plastic decreases in myelin also
      happen in the adult brain has been largely unexplored. Recently, Sinclair et al.
      (Sinclair JS, Fischl MJ, Alexandrova O, Hebeta M, Grothe B, Leibold C, and Kopp
      Scheinpflug C. J Neurosci 37: 8239-8255, 2017) have shown that auditory
      deprivation can lead to decrease in myelination and axon caliber even in healthy
      adulthood. These findings show that activity-regulated myelination is more
      complex than previously thought and expand our knowledge of how adult brain
      plasticity could operate on a cellular level.

PMID- 30207858
TI  - Cortico-cerebellar network involved in saccade adaptation.
AB  - Saccade adaptation is the learning process that ensures that vision and saccades
      remain calibrated. The central nervous system network involved in these adaptive
      processes remains unclear, due to difficulties isolating the learning process
      from the correlated visual and motor processes. Here, we imaged the human brain
      during a novel saccade adaptation paradigm that allowed us to isolate neural
      signals involved in learning independent of the changes in the amplitude of
      corrective saccades usually correlated with adaptation. We show that the changes
      in activation in the ipsiversive cerebellar vermis that track adaptation are not
      driven by the changes in corrective saccades, and thus provide critical
      supporting evidence for previous findings. Similarly, we find that activation in
      the dorsomedial wall of the contraversive precuneus mirrors the pattern found in
      the cerebellum. Finally, we identify dorsolateral and dorsomedial cortical areas
      in the frontal and parietal lobes that encode the retinal errors following
      inaccurate saccades used to drive recalibration. Together, these data identify a
      distributed network of cerebellar and cortical areas and their specific roles in
      oculomotor learning.

PMID- 30207859
TI  - Predicting responses to inhibitory synaptic input in substantia nigra pars
      reticulata neurons.
AB  - The changes in firing probability produced by a synaptic input are usually
      visualized using the post-stimulus time histogram (PSTH). It would be useful if
      postsynaptic firing patterns could be predicted from patterns of afferent
      synaptic activation, but attempts to predict the PSTH from synaptic potential
      waveforms using reasoning based on voltage trajectory and spike threshold have
      not been successful, especially for inhibitory inputs. We measured PSTHs for
      substantia nigra pars reticulata (SNr) neurons inhibited by optogenetic
      stimulation of striato-nigral inputs, or by matching artificial inhibitory
      conductances applied by dynamic clamp. The PSTH was predicted by a model based on
      each SNr cell's phase resetting curve (PRC). Optogenetic activation of striato
      nigral input or artificial synaptic inhibition produced a PSTH consisting of an
      initial depression of firing followed by oscillatory increases and decreases
      repeating at the SNr cell's baseline firing rate. The phase resetting model
      produced PSTHs closely resembling the cell data, including the primary pause in
      firing and the oscillation. Key features of the PSTH, including the onset rate
      and duration of the initial inhibitory phase, and the subsequent increase in
      firing probability could be explained from the characteristic shape of the SNr
      cell's PRC. The rate of damping of the late oscillation was explained by the
      influence of asynchronous phase perturbations producing firing rate jitter and
      wander. Our results demonstrate the utility of phase resetting models as a
      general method for predicting firing in spontaneously active neurons, and their
      value in interpretation of the striato-nigral PSTH.

PMID- 30207860
TI  - Motor imagery in multiple sclerosis: exploring applications in therapeutic
      treatment.
AB  - Motor imagery (MI) is a promising rehabilitation technique that has received
      significant interest for use in persons with multiple sclerosis (MS). Through
      alterations in neural networks, MI has the potential to improve measures of
      walking speed, walking distance, and fatigue in people with MS. Further research
      is required to assess the validity of MI in conjunction with other therapeutic MS
      treatments and provide objective outcome measures of motor improvements.

PMID- 30207861
TI  - Visual Information Processing in Older Adults: Reaction Time and Motor Unit Pool
      Modulation.
AB  - Currently, there is no evidence that magnification of visual feedback has motor
      implications beyond impairments in force control during a visuomotor task. We
      hypothesized that magnification of visual feedback would increase visual
      information processing, alter the muscle activation, and exacerbate the response
      time in older adults. To test this hypothesis, we examined whether magnification
      of visual feedback during a reaction time task alters the pre-motor time and the
      motor unit pool activation of older adults. Participants responded as fast as
      possible to a visual stimulus while they maintained a steady ankle dorsiflexion
      force (15% maximum) either with low-gain or high-gain visual feedback of force.
      We quantified the following: 1) response time and its components (pre-motor and
      motor time); 2) force variability; 3) motor unit pool activity of the tibialis
      anterior muscle. Older adults exhibited longer pre-motor time and greater force
      variability than young adults. Only in older adults, magnification of visual
      feedback lengthened the pre-motor time and exacerbated force variability. The
      slower pre-motor time in older adults with high-gain visual feedback was
      associated with increased force variability and an altered modulation of the
      motor unit pool. In conclusion, our findings provide novel evidence that
      magnification of visual feedback also exacerbates pre-motor time during a
      reaction time task in older adults, which is correlated with force variability
      and an altered modulation of motor unit pool. Thus, these findings suggest that
      visual information processing deficiencies in older adults could result in force
      control and reaction time impairments.

PMID- 30207862
TI  - Vestibular and corticospinal control of human body orientation in the
      gravitational field.
AB  - Body orientation with respect to the direction of gravity changes when we lean
      forward from upright standing. We tested the hypothesis that during upright
      standing, the nervous system specifies the referent body orientation that defines
      spatial thresholds for activation of multiple muscles across the body. To
      intentionally lean the body forward, the system is postulated to transfer balance
      and stability to the leaned position by monotonically tilting the referent
      orientation, thus increasing the activation thresholds of ankle extensors and
      decreasing their activity. Consequently, the unbalanced gravitational torque
      would start to lean the body forward. With re-stretching, ankle extensors would
      be re-activated and generate increasing EMG activity until the enhanced
      gravitational torque would be balanced at a new posture. As predicted, vestibular
      influences on motoneurons of ankle extensors evaluated by galvanic vestibular
      stimulation were smaller in the leaned compared to the upright position, despite
      higher tonic EMG activity. De-facilitation of vestibular influences was also
      observed during forward leaning when the EMG levels in the upright and leaned
      position were equalized by compensating the gravitational torque with a load. The
      vestibular system is involved in the active control of body orientation without
      directly specifying the motor outcome. Corticospinal influences originating from
      the primary motor cortex evaluated by transcranial magnetic stimulation remained
      similar at the two body postures. Thus, in contrast to the vestibular system, the
      corticospinal system maintains a similar descending facilitation of motoneurons
      of leg muscles at different body orientations. The study advances the
      understanding of how body orientation is controlled.

PMID- 30207863
TI  - Operant conditioning of the tibialis anterior motor evoked potential in people
      with and without chronic incomplete spinal cord injury.
AB  - The activity of corticospinal pathways is important in movement control and its
      plasticity is essential for motor skill learning and re-learning after CNS
      injuries. Thus, enhancing the corticospinal function may improve motor function
      recovery after CNS injuries. Operant conditioning of stimulus-induced muscle
      responses (e.g., reflexes) is known to induce the targeted plasticity in a
      targeted pathway. Thus, an operant conditioning protocol to target the
      corticospinal pathways may be able to enhance the corticospinal function. To test
      this possibility, we investigated whether operant conditioning of the tibialis
      anterior (TA) motor evoked potential (MEP) to transcranial magnetic stimulation
      can enhance corticospinal excitability in people with and without chronic
      incomplete SCI. The protocol consisted of 6 baseline and 24 up
      conditioning/control sessions over 10 weeks. In all sessions, TA MEPs were
      elicited at 10% above active MEP threshold while the sitting participant provided
      a fixed preset level of TA background EMG. During baseline sessions, MEPs were
      simply measured. During conditioning trials of the conditioning sessions, the
      participant was encouraged to increase MEP, and was given immediate feedback
      indicating whether MEP size was above a criterion. In 5/8 participants without
      SCI and 9/10 with SCI, over 24 up-conditioning sessions, MEP size increased
      significantly to ~150% of the baseline value, while the silent period duration
      decreased by ~20%. In a control group of participants without SCI, neither MEP
      nor SP changed. These results indicate that MEP up-conditioning can facilitate
      corticospinal excitation, which is essential for enhancing motor function
      recovery after SCI.

PMID- 30207864
TI  - Automatic Spike Sorting Algorithm for High-Density Microelectrode Arrays.
AB  - High-density microelectrode arrays (HD-MEAs) can be used to record extracellular
      action potentials from hundreds to thousands of neurons simultaneously. Efficient
      spike-sorters have to be developed to cope with such large data volumes. Most
      existing spike sorting methods for single electrodes or small multi-electrodes,
      however, suffer from the "curse of dimensionality", and cannot be directly
      applied to recordings with hundreds of electrodes. This holds particularly true
      for the standard reference spike sorting algorithm, principal-component-analysis
      based feature extraction, followed by k-means or expectation maximization
      clustering, against which most spike-sorters are evaluated. We present a spike
      sorting algorithm that circumvents the dimensionality problem by sorting local
      groups of electrodes independently using classical spike sorting approaches. It
      is scalable to any number of recording electrodes and well suited for parallel
      computing. The combination of data pre-whitening before the principal-component
      analysis-based extraction and a parameter-free clustering algorithm obviated the
      need for parameter adjustments. We evaluated its performance using surrogate data
      in which we systematically varied spike amplitudes and spike rates and which were
      generated by inserting template spikes into the voltage traces of real
      recordings. In a direct comparison, our algorithm could compete with existing
      state-of-the-art spike sorters in terms of sensitivity and precision, while
      parameter adjustment or manual cluster curation were not required.

PMID- 30207865
TI  - Relative sensitivity of explicit re-aiming and implicit motor adaptation.
AB  - It has become increasingly clear that learning in visuomotor rotation tasks,
      which induce an angular mismatch between movements of the hand and visual
      feedback, largely results from the combined effort of two distinct processes:
      implicit motor adaptation and explicit re-aiming. However, it remains unclear how
      these two processes work together to produce trial-by-trial learning. Previous
      work has found that implicit motor adaptation operates automatically, regardless
      of task relevancy, and saturates for large errors. In contrast, little is known
      about the automaticity of explicit re-aiming and its sensitivity to error
      magnitude. Here we sought to characterize the automaticity and sensitivity
      function of these two processes to determine how they work together to facilitate
      performance in a visuomotor rotation task. We found that implicit adaptation
      scales relative to the visual error, but only for small perturbations -
      replicating prior work. In contrast, explicit re-aiming scales linearly for all
      tested perturbation sizes. Furthermore, the consistency of the perturbation
      appears to diminish both implicit adaptation and explicit re-aiming, but to
      different degrees. Whereas implicit adaptation always displayed a response to the
      error, explicit re-aiming was only engaged when errors displayed a minimal degree
      of consistency. This comports with the idea that implicit adaptation is
      obligatory and less flexible, while explicit re-aiming is volitional and
      flexible.

PMID- 30207866
TI  - Dynamic population coding and its relationship to working memory.
AB  - For over 45 years, neuroscientists have conducted experiments aimed at
      understanding the neural basis of working memory. Early results examining
      individual neurons highlighted that information is stored in working memory in
      persistent sustained activity where neurons maintained elevated firing rates over
      extended periods of time. However, more recent work has emphasized that
      information is often stored in working memory in dynamic population codes, where
      different neurons contain information at different periods in time. In this paper
      we review findings that show that both sustained activity as well as dynamic
      codes are present in the prefrontal cortex and other regions during memory delay
      periods. We also review work showing that dynamic codes are capable of supporting
      working memory, and that such dynamic codes could easily be 'readout' by
      downstream regions. Finally, we discuss why dynamic codes could be useful for
      enabling animals to solve tasks that involve working memory. While additional
      work is still needed to definitively know whether dynamic coding is critical for
      working memory, the findings reviewed here give insight into how different codes
      could contribute to working memory, which should be useful for guiding future
      research.

PMID- 30207867
TI  - The Effect of Cervico-lumbar Coupling on Spinal Reflexes during Cycling after
      Incomplete Spinal Cord Injury.
AB  - Spinal networks in the cervical and lumbar cord are actively coupled during
      locomotion to coordinate arm and leg activity. The goals of this project were to
      investigate the intersegmental cervico-lumbar connectivity during cycling after
      incomplete spinal cord injury (iSCI), and assess the effect of rehabilitation
      training on improving reflex modulation mediated by cervico-lumbar pathways. Two
      studies were conducted. In the first, 22 neurologically intact (NI) people and 10
      people with chronic iSCI were recruited. The change in H-reflex amplitude in
      flexor carpi radialis (FCR) during leg cycling and H-reflex amplitude in soleus
      (SOL) during arm cycling were investigated. In the second study, two groups of
      participants with chronic iSCI underwent 12 weeks of cycling training: one
      performed combined arm and leg cycling (A&L) and the other legs only cycling
      (Leg). The effect of training paradigm on the amplitude of the SOL H-reflex was
      assessed. Significant reduction in the amplitude of both FCR and SOL H-reflexes
      during dynamic cycling of the opposite limbs was found in NI participants, but
      not in participants with iSCI. Nonetheless, there was a significant reduction in
      the SOL H-reflex during dynamic arm cycling in iSCI participants after training.
      Substantial improvements in SOL H-reflex properties were found in the A&L group
      after training. The results demonstrate that cervico-lumbar modulation during
      rhythmic movements is disrupted in people with chronic iSCI; however, this
      modulation is restored after cycling training. Furthermore, involvement of the
      arms simultaneously with the legs during training may better regulate the leg
      spinal reflexes.

PMID- 30207868
TI  - Context-dependent tactile texture-sensitivity in monkey M1 and S1 cortex.
AB  - Caudal primary motor cortex (M1, area 4) is sensitive to cutaneous inputs but the
      extent to which the physical details of complex stimuli are encoded is not known.
      We investigated the sensitivity of M1 neurones (4 Macaca mulatta monkeys) to
      textured stimuli (smooth/rough or rough/rougher) during the performance of a
      texture discrimination task and, for some cells, during a No task condition (same
      surfaces; no response). The recordings were made from the hemisphere
      contralateral to the stimulated digits; the motor response (sensory decision) was
      made with the non stimulated arm. Most M1 cells were modulated during surface
      scanning in the Task, 88%, but few of these were texture-related, 24%. In
      contrast, 44% of M1 neurones were texture-related in the No task condition.
      Recordings from the neighbouring primary somatosensory cortex (S1), the potential
      source of texture-related signals to M1, showed that S1 neurones were
      significantly more likely to be texture-related during the Task, 57 vs 24%, than
      M1. No difference was observed in the No task condition (52 vs 44%). In these
      recordings, the details about surface texture were relevant for S1 but not for
      M1. We suggest that tactile inputs to M1 were selectively suppressed when the
      animals were engaged in the Task. S1 was spared these controls as the same inputs
      were task-relevant. Taken together we suggest that the suppressive effects are
      most likely exerted directly at the level of M1, possibly through the activation
      of a top-down gating mechanism specific to motor set/intention.

PMID- 30207869
TI  - Emerging roles of circRNA_NEK6 targeting miR-370-3p in the proliferation and
      invasion of thyroid cancer via Wnt signaling pathway.
AB  - OBJECTIVE: To identify the significantly altered circRNAs and mRNAs in thyroid
      cancer, investigate their target miRNAs and determine their biological functions.
      METHODS: The differentially expressed circRNAs, mRNAs and pathways in thyroid
      cancer were identified by microarray analysis and gene set enrichment analysis
      (GSEA). The correlative circRNAs and mRNAs were found out through Pearson
      correlative analysis. The common target miRNAs of circNEK6 and FZD8 related to
      thyroid cancer was screened out through Targetscan, miRanda and HMDD analysis.
      The mRNA and protein expressions in thyroid cancer tissues and cells were
      detected by qRT-PCR and western blot. CircRNA was confirmed by the RNase R
      digestion and nucleic acid electrophoresis. The target relationships were
      verified by the dual luciferase reporter assay. Cell viability, invasion and
      apoptosis were determined by MTT assay, Transwell assay and flow cytometry,
      respectively. RESULTS: CircNEK6 and FZD8 were significantly up-regulated in
      thyroid cancer, with strong correlations. The Wnt signaling pathway was activated
      in thyroid cancer. MiR-370-3p was the common target miRNA of circNEK6 and FZD8,
      and it was down-regulated in thyroid cancer. Overexpression of circNEK6 and FZD8
      could promote the growth and invasion of thyroid cancer cells, while up
      regulation of miR-370-3p could suppress thyroid cancer progression and inhibit
      the Wnt signaling pathway. MiR-370-3p's effect on thyroid cancer cells could be
      rescued by circNEK6 or FZD8. CONCLUSION: CircNEK6 promoted the progression of
      thyroid cancer through up-regulating FZD8 and activating Wnt signaling pathway by
      targeting miR-370-3p.

PMID- 30207870
TI  - Treatment of spinal cord compression caused by C2 osteochondroma with
      reconstruction and fusion after total resection: Case report and literature
      review.
AB  - CONTEXT: Osteochondroma is the most common benign tumor of the bone, but spinal
      osteochondroma is rare. We report a case of cervical osteochondroma in multiple
      exostoses arising from the lamina of the C2 vertebra, presenting with features of
      compressive myelopathy in a 22-year-old male. Total resection of the tumor and
      atlantoaxial fixation and fusion after reconstruction of the C1 posterior arch
      were performed. FINDINGS: The patient recovered significantly. He was
      asymptomatic and no sign of recurrence was observed after one-year follow-up.
      CONCLUSIONS: Osteochondroma should be considered as a rare cause of spinal cord
      compression. Entire removal of the tumor will result in complete decompression
      and can reduce the risk of recurrence. We provide a new approach to reconstruct
      after resection.

PMID- 30207871
TI  - Human-Biting Ixodes Ticks and Pathogen Prevalence from California, Oregon, and
      Washington.
AB  - From July 2006 through August 2017, a passive surveillance study of Ixodes ticks
      submitted from California, Oregon, and Washington was conducted by the TickReport
      program at the University of Massachusetts, Amherst. In total, 549 human-biting
      Ixodes ticks were submitted comprising both endemic and nonendemic species. We
      found that 430 endemic ticks were from 3 Ixodes species: Ixodes pacificus, Ixodes
      spinipalpis, and Ixodes angustus, whereas Ixodes scapularis (n = 111) was the
      most common species among the 119 nonendemic ticks. The submission peak for
      nymphal I. pacificus and I. spinipalpis was June, while submission peak for adult
      I. pacificus and nymphal I. angustus was April and September, respectively.
      Endemic ticks commonly attached to the lower extremities of their victims, and
      individuals younger than 9 years old were frequently bitten. The infection
      prevalence of Borrelia burgdorferi sensu lato, Borrelia miyamotoi, and Anaplasma
      phagocytophilum in I. pacificus ticks was 1.31%, 1.05%, and 0.52%, respectively,
      and the prevalence of B. burgdorferi s. l. and A. phagocytophilum in I.
      spinipalpis ticks was 14.29% and 10.71%, respectively. Furthermore, two species
      within the B. burgdorferi s. l. complex were detected in West Coast ticks: B.
      burgdorferi sensu stricto and Borrelia lanei. I. spinipalpis had the highest
      Borrelia prevalence among endemic ticks, and it was caused exclusively by B.
      lanei. Borrelia mayonii, Babesia microti, and Ehrlichia muris-like agent were not
      detected in these endemic ticks. In this study, we show that many nonendemic
      Ixodes ticks (119/549) are most likely acquired from travel to a different
      geographic region. We report cases of conventionally recognized nonhuman feeders
      (I. spinipalpis and I. angustus) parasitizing humans. The highest pathogen
      prevalence in I. spinipalpis may indicate a larger public health threat than
      previously thought, and the enzootic life cycle and pathogenicity of B. lanei
      warrant further study.

PMID- 30207872
TI  - Four new Tuber species added to the Rufum group from China based on morphological
      and molecular evidence.
AB  - Four new species, Tuber crassitunicatum, T. lishanense, T. piceatum, and T.
      wanglangense, are described and illustrated based on both morphological and
      molecular data. Morphologically, T. crassitunicatum is diagnosed by its brown
      ascomata and ellipsoidal ascospores ornamented by crowded spiny reticulum with
      more than 10 meshes across the spore width. Tuber lishanense can be recognized by
      its whitish to pale brown ascomata with a basal cavity, and very broadly
      ellipsoidal to subglobose ascospores ornamented by densely isolated spines. Tuber
      piceatum differs in its pale white ascomata and ellipsoidal ascospores with
      isolated spines, whereas T. wanglangense is characterized by its broad
      ellipsoidal ascospores with short spines that are connected by lower ridges when
      examined under scanning electron microscope (SEM). Phylogenetic analyses inferred
      the four new species in the Rufum group. Each species had less than 96%
      similarity in the internal transcribed spacer (ITS1-5.8S-ITS2) nuc rDNA ITS
      sequence to other Tuber species and represented a unique terminal clade in the
      phylogenetic tree. Our research did not confirm the occurrence in China of the
      European T. rufum and T. nitidum and the North American T. lyonii, although they
      are often reported in the literature on Chinese Tuber species.

PMID- 30207873
TI  - Association between incongruence about survivor function and outcomes among
      stroke survivors and family caregivers.
AB  - BACKGROUND: Stroke survivors and family caregivers often have incongruent
      appraisals of survivor cognitive, physical, and psychosocial function. Partner
      incongruence contributes to poor outcomes for survivors and caregivers.
      OBJECTIVES: This study explored whether partner incongruence: (1) differs by
      function domain; (2) increases or decreases over time, and; (3) is associated
      with self-rated health, distress, stress, and depressive symptoms. METHODS:
      Structured surveys were administered to 32 survivors and caregivers at
      approximately 3 (enrollment) and 7 months (follow-up) post-stroke. Paired t-tests
      were used to examine partners' ratings of survivor function at enrollment and
      follow-up, and changes in incongruence over time. Partial correlations were used
      to examine the association between incongruence at enrollment and outcomes at
      follow-up. RESULTS: Survivors consistently rated their own memory and thinking as
      significantly better than caregivers rated their memory and thinking. At follow
      up, survivors rated their own communication as significantly better than
      caregivers rated their communication. Incongruence about survivor memory and
      thinking was associated with survivor distress, as well as caregiver distress,
      stress, and depressive symptoms. Incongruence about survivor ADLs was associated
      with caregiver stress and depressive symptoms. Incongruence about survivor social
      participation was associated with caregiver distress. CONCLUSIONS: Findings from
      this study suggest that survivors and caregivers often have incongruent
      appraisals of survivor function, that incongruence does not improve naturally
      over time, and that incongruence may be detrimental for survivor and caregiver
      outcomes. Further research should be directed at the mitigation of incongruence
      and strategies to improve outcomes for both survivors and family caregivers.

PMID- 30207874
TI  - Use of ventilation bag for the respiratory support during magnetic resonance
      imaging in Arnold-Chiari ventilated patients, a case report.
AB  - CONTEXT: Magnetic Resonance Imaging (MRI) is an essential diagnostic tool for
      neuroimaging tissues such as the spinal cord. Unfortunately, the use of MRI may
      be limited in ventilated patients, who cannot maintain the supine position in
      spontaneous breathing for the whole duration of the exam (i.e. neuro-muscular
      patients with diaphragm involvement). The use of MRI-compatible ventilator during
      MRI could be a solution but they are not universally available. Furthermore,
      their performances are not up to those of the conventional ones and they are not
      always compatible with Non Invasive Ventilation (NIV). FINDINGS: This case report
      describes an easy and low-cost solution to ventilate a patient non-invasively
      during the MRI procedure. The patient in this case was a 45-yr-old man,
      wheelchair-dependent and chronically ventilated in NIV with a forced vital
      capacity in supine position of 370 ml (10% of predicted normal), affected by
      Arnold-Chiari Syndrome, and in need of a MRI diagnostic control. CONCLUSION: The
      technique proposed, that does not affect the MRI images quality, consists in
      ventilating the patient using a simple nonmetallic Ventilation Bag, operated by a
      Respiratory Therapist. This has been proven a useful and economical solution for
      ventilatory support during MRI for a respiratory-dependent patient with Arnold
      Chiari Syndrome.

PMID- 30207875
TI  - Prognostic validity of a clinical trunk control test for independence and walking
      in individuals with spinal cord injury.
AB  - OBJECTIVE: The objective of the present work was to determine the prognostic
      validity of the trunk control test for walking and independence in individuals
      with SCI. DESIGN: A cohort, prospective study was carried out in all individuals
      with sub-acute SCI. SETTING: All inpatients at the Mexico City based National
      Rehabilitation Institute (INR). PARTICIPANTS: Ninety individuals with a clinical
      diagnosis of sub-acute SCI, American Spinal Injury Association Impairment Scale
      (AIS) A-D, and that have not participated in a rehabilitation program were
      included. Thirty-five individuals had good initial trunk control and the
      remaining 55 had poor trunk control. All individuals participated in a standard
      rehabilitation program subsequently. INTERVENTIONS: N/A Outcome Measures: The
      trunk control test was performed at baseline. At 1, 3, 6, 9 and 12 months after
      the first evaluation, walking and independence were assessed. RESULTS: Survival
      Analysis revealed that 62.5% and 100% individuals with good trunk control at
      baseline assessment were respectively walking and independent in ADL at 12 months
      and 14% and 48% individuals with poor trunk control were walking and independent
      in ADL. Cox regression analysis revealed that individuals with good trunk control
      were 4.6 times more likely to walk independently at 12 months and 2.9 times more
      likely to be independent in activities of daily living. CONCLUSION: The present
      study revealed that the trunk control test is useful for providing a prognosis of
      independence and walking at 1 year in individuals with SCI, independently of the
      neurologic level and the severity of the injury.

PMID- 30207876
TI  - Changing Geographic Distribution of Japanese Encephalitis Virus Genotypes, 1935
      2017.
AB  - Japanese encephalitis virus (JEV) is a representative virus of the JEV serogroup
      in genus Flavivirus, family Flaviviridae. JEV is a mosquito-borne virus that
      causes Japanese encephalitis (JE), one of the most severe viral encephalitis
      diseases in the world. JEV is divided into five genotypes (G1-G5), and each
      genotype has its own distribution pattern. However, the distribution of different
      JEV genotypes has changed markedly in recent years. JEV G1 has replaced G3 as the
      dominant genotype in the traditional epidemic areas in Asia, while G3 has spread
      from Asia to Europe and Africa and caused domestic JE cases in Africa. G2 and G5,
      which were endemic in Malaysia, exhibited great geographical changes as well. G2
      migrated southward and led to prevalence of JE in Australia, while G5 emerged in
      China and South Korea after decades of silence. Along with these changes, JE
      occurred in some non-traditional epidemic regions as an emerging infectious
      disease. The regional changes in JEV pose a great threat to human health, leading
      to huge disease burdens. Therefore, it is of great importance to strengthen the
      monitoring of JEV as well as virus genotypes, especially in non-traditional
      epidemic areas.

PMID- 30207877
TI  - Emotional security theory: An application to sibling bereavement.
AB  - There is a need for guiding theory to understand the experiences and outcomes of
      bereaved siblings, particularly from a family systems framework. The present
      study investigated the relevance of emotional security theory in a sample of 72
      young adults who experienced sibling bereavement. We investigated (1) whether
      perceptions of prolonged parental grief predicted key aspects of emotional
      security (disengagement, preoccupation, and security), and (2) whether emotional
      security mediated a relation between perceptions of prolonged parental grief and
      young adult emotional functioning. Results supported the potential utility of
      emotional security theory as a theoretical framework for understanding sibling
      bereavement.

PMID- 30207878
TI  - Implementation Science and the Leading Edge.

PMID- 30207879
TI  - The Nurse as Researcher.

PMID- 30207880
TI  - Whose Job Is It? Planning for Clinical Palliative Care in a Typical Health System
      in the United States.

PMID- 30207882
TI  - Tattooed and Told: Stories on Skin.

PMID- 30207881
TI  - Conservative Treatment of Ruptured Thoracoabdominal Aortic Aneurysm in
      Hemodialysis Patient.

PMID- 30207883
TI  - Complexity Science and Palliative Care: Drawing from Complex Adaptive Systems
      Theories to Guide Our Successes.

PMID- 30207884
TI  - Palliative Care Issues for Transfusion-Dependent Patients #359.

PMID- 30207885
TI  - T-Shirt Days.

PMID- 30207886
TI  - Mindful Movement: Tai Chi, Gentle Yoga, and Qi Gong for Hospitalized Pediatric
      Palliative Care Patients and Family Members.

PMID- 30207888
TI  - Recent Literature.

PMID- 30207887
TI  - Nonoral Routes of Methadone for Analgesia in Palliative Care #358.

PMID- 30207889
TI  - Chaplaincy in Hospice and Palliative Care.

PMID- 30207890
TI  - Time Travel.

PMID- 30207891
TI  - Evaluation of Bacteriophage Anti-Biofilm Activity for Potential Control of
      Orthopedic Implant-Related Infections Caused by Staphylococcus Aureus.
AB  - BACKGROUND: Despite significant advancements in surgical protocols and
      biomaterials for orthopedics, peri-prosthetic joint infection (PJI) remains a
      leading cause of implant failure. Staphylococcus aureus nasal colonization is an
      established risk factor for PJI, with methicillin-sensitive S. aureus a leading
      cause of orthopedic implant-related infections. The purpose of these in vitro
      studies was to investigate the antibacterial activity of a tailored bacteriophage
      cocktail against planktonic and biofilm-associated S. aureus. METHODS: The S.
      aureus strains (n = 30) were screened for their susceptibility to a library of S.
      aureus-specific bacteriophage (n = 31). Five bacteriophage preparations that
      demonstrated bactericidal activity against >90% of S. aureus strains tested were
      combined as a StaPhage cocktail and assessed for their antibacterial activity
      toward planktonic and biofilm-associated S. aureus, with biofilms established on
      three-dimensional-printed porous titanium scaffolds. RESULTS: StaPhage treatment
      immediately after bacterial inoculation inhibited growth of S. aureus by >98% in
      eight hour cultures when multiplicity of infection of phages to bacteria was
      greater than 1:1 (p < 0.01). Viable bacterial numbers within biofilms on titanium
      surfaces were significantly reduced (6.8 log10 to 6.2 log10 colony forming units
      [CFU]; p < 0.01) after exposure to the StaPhage cocktail, in vitro. No
      significant reduction was observed in biofilms exposed to 100 times the minimal
      inhibitory concentration of cefazolin (log10 6.81 CFU). CONCLUSIONS: Combined,
      these data demonstrate the in vitro efficacy of S. aureus-specific bacteriophage
      cocktails against S. aureus growing on porous titanium and warrant further in
      vivo studies in a clinically relevant animal model to evaluate the potential
      application of bacteriophage in the management of PJI caused by S. aureus.

PMID- 30207892
TI  - Social prescribing: an essential but neglected component of the undergraduate
      medical curriculum.

PMID- 30207893
TI  - Leprosy Diagnosed Via Teledermatology in a U. S. Urban Academic Health Center
      Highlights Potential Benefits and a Pitfall of Existing Telemedicine Services.
AB  - PURPOSE: Teledermatology has emerged as an important tool to extend the reach of
      dermatologists. As utilization of teledermatology services increases, careful
      attention should be given to the design of the system for consulting
      dermatologists. METHODOLOGY: In this case study, we report how access to a
      patient's entire medical history in a teledermatology consultation was vital for
      an accurate diagnosis. RESULTS: This case emphasizes the importance of full
      access to patients' medical records for improving diagnostic accuracy. We believe
      that full-access systems will lower the risk of misdiagnosis and will help to
      maximize the potential of teledermatology.

PMID- 30207894
TI  - Moderate-to-vigorous physical activity and the risk of stroke recurrence in
      patients with a history of minor ischemic stroke in Japan: a retrospective
      analysis.
AB  - BACKGROUND: Physical activity (PA) is beneficial for stroke prevention; in
      particular, moderate-to-vigorous physical activity (MVPA). However, few studies
      have investigated its relationship with recurrent ischemic stroke (RIS).
      OBJECTIVES: To clarify the relationship between MVPA and RIS and the burden of
      risk factors after a first-ever ischemic stroke. METHODS: A total of 45
      outpatients (mean age 67.1 +/- 10.2 years) who had previously experienced a
      transient ischemic attack or a minor non-cardioembolic ischemic stroke at a
      single hospital in Japan (mean 6.4 +/- 4.2 years previously), were enrolled
      between March and June 2016. All patients wore an accelerometer around their hips
      for 10 days, and their percentage body fat (%BF) and visceral fat level (VFL)
      were measured by bioelectrical impedance. Retrospective information about the
      history of RIS and risk factors (blood pressure, lipoprotein cholesterol and
      estimated glomerular filtration rate) were extracted from the clinical records.
      Binary logistic regression models were used to estimate the relevance of the RIS
      history to MVPA and potential risk factors such as sociodemographic and clinical
      variables (obesity, smoking and hypertension). RESULTS: RIS occurred in 9
      patients; they had significantly higher VFL (p = 0.007) and %BF (p = 0.007)
      values and lower MVPA (p = 0.011) values than patients without recurrence. A
      multivariate analysis of these factors indicated that age, VFL and MVPA were
      significant independent predictors of RIS. CONCLUSIONS: Patients with a history
      of mild ischemic stroke had low MVPA and high VFL values, which together may be a
      risk factor for RIS.

PMID- 30207895
TI  - Core food model of the Taiwan food supply for total diet study.
AB  - Following the core food (CF) models of the USA and France reported in the 2000s,
      this study presents the first oriental CF model, for total diet studies in
      Taiwan. First, we combined the four latest national dietary recall surveys from
      2005 to 2012, data sets from the Nutrition and Health Survey in Taiwan (NAHSIT)
      covering all ages (1 to 65+ years old). In total, 3,098 NAHSIT food codes from
      349,497 records of responses from 7,580 individuals were aggregated within a
      three-tiered scheme into 237 CFs in 54 subcategories and 16 categories. As with
      Western foods, Taiwanese foods were mainly aggregated by food type and major
      ingredient, processing method, cooking method or serving habit. In addition, we
      propose several categories typical to Taiwanese foods: (1) processed foods (e.g.
      rice paste, rice noodle, bean curd); (2) mixed foods (e.g. tomato fried with egg,
      Guangdong porridge) and stuffed staple foods (e.g. rice cake, zongzi); (3)
      Chinese Dim Sum (e.g. dumpling, salted bun); and (4) animal offal (e.g. pig
      liver, chicken kidney) and by-products (e.g. chicken head, pig foot). Systematic
      nomenclature and coding methods are also proposed. A computerised web model was
      developed using a graphical user interface (GUI) for automatic CF aggregation and
      inquiry of various consumption estimates according to the residing area, age
      group, and gender of consumers. Point estimates of weighted means were calculated
      for consumption rates (CR) based on the whole group (WG) or consumers only (CO).
      The CR and body weight (BW) of each individual were matched to calculate mean
      intake per unit body weight (g/kg bw/day). A general sample design procedure with
      the CF model is suggested for a total diet study (TDS) on target hazards.
      Strategies are also discussed for improving the quality of food matching in
      sample designs.

PMID- 30207896
TI  - Nutrition Risk Measured Online in Community-Living Older Australians.
AB  - Many community-living older adults experience the condition of malnutrition and
      the causes are complex and multi-factorial. This study examined nutrition risk in
      a sample of community-living older Australians (n = 77, age >=65 years) using an
      online, self-administered survey consisting of two validated questionnaires
      (SCREEN II and SF-12). We found a significant relationship between health status
      and nutrition risk; those with higher self-rated health status had lower
      nutrition risk. Forty percent of the participants were categorized at high
      nutritional risk, 26% at moderate nutritional risk and 34% not at nutritional
      risk. The most common nutrition risk factors were: (i) weight perception
      (perceiving weight to be more than it should); (ii) food avoidance; (iii) low
      intake of milk, milk products and alternatives; and (iv) finding meal preparation
      a chore. Many nutrition-risk factors were consistent with population survey data
      highlighting the need for greater awareness of nutritional requirements for
      healthy ageing.

PMID- 30207898
TI  - New Sources of Adult Plant and Seedling Resistance to Puccinia coronata f. sp.
      avenae Identified among Avena sativa Accessions From the National Small Grains
      Collection.
AB  - Accessions of cultivated oat (Avena sativa L.) from the United States Department
      of Agriculture-Agricultural Research Service Small Grains Collection in Aberdeen,
      ID were characterized for adult plant resistance (APR) and seedling resistance to
      crown rust, caused by Puccinia coronata f. sp. avenae. Initially, 607 oat
      accessions with diverse geographic origins were evaluated in field tests in Baton
      Rouge, LA. Of those, 97 accessions were not fully susceptible and were tested in
      the field in St. Paul, MN against a diverse P. coronata f. sp. avenae population.
      Thirty-six accessions that had some level of resistance in both field tests and
      mean coefficients of infection of <=20 were further evaluated for APR and
      seedling resistance. Among these, four accessions (PI 193040, PI 194201, PI
      237090, and PI 247930) were resistant to eight P. coronata f. sp. avenae races as
      seedlings. Twenty-nine accessions had resistance to at least one of the P.
      coronata f. sp. avenae races. Three accessions (CIav 2272, CIav 3390, and PI
      285583) were fully susceptible to all eight P. coronata f. sp. avenae races as
      seedlings. Further evaluation of the three seedling-susceptible accessions at the
      flag leaf stage in a growth chamber resulted in moderately susceptible to
      moderately resistant responses. The resistance sources presented here may contain
      genes not deployed in elite oat varieties, and may be useful for future crown
      rust resistance breeding. The adult and seedling resistance found in accessions
      of the cultivated oat species is especially valuable because it avoids problems
      associated with the transfer of genes from wild species to cultivated oat.

PMID- 30207897
TI  - Educational training requirements for general practice/family medicine specialty
      training: recommendations for trainees, trainers and training institutions.
AB  - High-quality training is a prerequisite to teaching future general practitioners.
      To inspire and guide all countries to implement General Practice (GP) specialist
      education and training and bring it to the highest standards, we aimed, within
      the European context, to produce a collaborative document entitled 'Educational
      Requirements for GP Specialty Training'. Through an iterative process existing
      documents from the European Academy of Teachers in GP and Family Medicine
      (EURACT) and the World Organization of Family Medicine Doctors (WONCA) were
      collated. Other reports, grey literature about specialty GP training and
      requirements for trainees, trainers and training institutions were included.
      State-of-the-art GP specialty training 'core' competences, characteristics and
      essential features of GP are described. General principles and specified tools
      for training and assessment are summarised. Recommendations on the duration and
      place(s) of training and selection of trainees are provided. Trainers should be
      accredited teachers and quality training institutions are essential. New
      insights, existing gaps and issues for debate have highlighted areas for further
      research. This document was produced in the specific context of Europe but its
      general principles are relevant to GP training in all countries.

PMID- 30207899
TI  - Viral Metagenomic-Based Screening of Sugarcane from Florida Reveals Occurrence of
      Six Sugarcane-Infecting Viruses and High Prevalence of Sugarcane yellow leaf
      virus.
AB  - A viral metagenomics study of the sugarcane virome in Florida was carried out in
      2013 to 2014 to analyze occurrence of known and potentially new viruses. In
      total, 214 sugarcane leaf samples were collected from different commercial
      sugarcane (Saccharum interspecific hybrids) fields in Florida and from other
      Saccharum and related species taken from two local germplasm collections. Virion
      associated nucleic acids (VANA) metagenomics was used for detection and
      identification of viruses present within the collected leaf samples. VANA
      sequence reads were obtained for 204 leaf samples and all four previously
      reported sugarcane viruses occurring in Florida were detected: Sugarcane yellow
      leaf virus (SCYLV, 150 infected samples out of 204), Sugarcane mosaic virus (1 of
      204), Sugarcane mild mosaic virus (13 of 204), and Sugarcane bacilliform virus
      (54 of 204). High prevalence of SCYLV in Florida commercial fields and germplasm
      collections was confirmed by reverse-transcription polymerase chain reaction.
      Sequence analyses revealed the presence of SCYLV isolates belonging to two
      different phylogenetic clades (I and II), including a new genotype of this virus.
      This viral metagenomics approach also resulted in the detection of a new
      sugarcane-infecting mastrevirus (recently described and named Sugarcane striate
      virus), and two potential new viruses in the genera Chrysovirus and Umbravirus.

PMID- 30207900
TI  - Plant Volatiles Reduce the Viability of the Root-Knot Nematode Meloidogyne
      incognita Either Directly or When Retained in Water.
AB  - Volatile organic compounds (VOC) produced by green residues for the management of
      plant-parasitic nematodes are poorly studied for oilseed plants and some Brassica
      spp. To investigate the activity of VOC in vitro and as biofumigants, dry and
      aqueous macerates of broccoli (Brassica oleracea var. italica) shoots and
      sunflower (Helianthus annuus) seed were used against the root-knot nematode
      Meloidogyne incognita. VOC produced by sunflower seed caused higher mortality of
      M. incognita second-stage juveniles (J2) than VOC produced by broccoli shoots but
      both plant species were equally effective in decreasing the infectivity and
      reproduction of this nematode. The number of galls and eggs produced by the
      nematode in tomato roots was reduced by 89 and 95%, respectively, on average, at
      the highest concentrations of broccoli and sunflower seed macerates tested as
      biofumigants. When nematodes were placed in water exposed to broccoli VOC, J2
      immobility increased and the number of galls and eggs produced by the nematode in
      tomato roots decreased 80 and 96%, respectively. Water exposed to sunflower seed
      VOC had no effect on the viability of the nematode. Gas chromatography was used
      to identify five and six chemical groups in broccoli and in sunflower seed
      macerates, respectively, but only alcohols, sulfurated VOC, and terpenes were
      detected in the water exposed to these plant macerates. Sulfurated VOC from the
      water exposed to broccoli macerates were found to be involved in its activity
      against M. incognita. The purified VOC dimethyl disulfide (DMDS) and 3-pentanol
      were tested directly against J2 and showed a lethal concentration of 176 and 918
      ug/ml (ppm), respectively, whereas dimethyl sulfide had no effect against M.
      incognita. Furthermore, DMDS and 3-pentanol retained in water killed J2 and
      reduced gall formation and the number of eggs of M. incognita on tomato roots.
      Both these plant species produced toxic VOC to M. incognita, whereas only VOC
      retained in water exposed to broccoli had activity against M. incognita.

PMID- 30207901
TI  - Mexico's Seguro Popular: Achievements and Challenges.
AB  - In Mexico, Seguro Popular is a landmark government program aimed to guarantee
      universal access to health services, especially for the most vulnerable
      populations. Since its adoption in 2004, important changes have been made to
      improve the performance of Seguro Popular. In this article, we present the main
      changes that have been implemented in Seguro Popular during the current
      administration (2012-2018) and propose a series of considerations to improve its
      performance in the immediate future and thus contribute to achieving the goal of
      universal health coverage in Mexico.

PMID- 30207902
TI  - Can Ethiopia Finance the Continued Development of Its Primary Health Care System
      If External Resources Decline?
AB  - Ethiopia's recent improvements in health outcomes benefited from the large
      increase in development assistance for health received in recent years, most of
      which supported its primary care system. Increased domestic resource mobilization
      for health will be needed to sustain progress given recent and likely future
      declines in external support. We estimate a projection model of Ethiopian
      government domestic resource mobilization potential compared with future health
      care delivery costs in order to assess Ethiopia's ability to finance its planned
      primary health care system. For the period of Ethiopia's current five-year health
      sector plan (2016-2020), the projection model indicates that if real external
      resources remain at the levels of 2011, domestic resource mobilization may only
      provide half of the estimated funds needed. Including out-of-pocket spending
      currently captured as retained user fees, Ethiopia is more likely to successfully
      finance continued delivery of primary care. Over 20 years, 2016-2035, the future
      sustainability of primary care services without increasing contributions from
      households will depend largely on significant economic growth and more government
      funding for primary care. Our modeling suggests that Ethiopia can substantially
      support further development of primary care services, even in the face of
      declining external support. However, it is unlikely to achieve its goals solely
      through "business as usual." Ethiopia is already moving forward with timely
      adoption of sound strategies to maintain progress. External partners should
      support these trends to enable transition plans to greater domestic funding with
      minimal disruption to positive progress that has been and is being made.

PMID- 30207903
TI  - Introduction to Health Systems & Reform 4(3).

PMID- 30207904
TI  - The Core Roles of Transparency and Accountability in the Governance of Global
      Health Public-Private Partnerships.
AB  - This article introduces a simplified model for assessing and designing the
      governance of global health public-private partnerships (PPPs) based on the two
      concepts of transparency and accountability. The article reviews the literature
      on partnership governance, which shows many frameworks and recommendations but
      limited implementation of the proposals. The article proposes a matrix to provide
      a high-level analytical and planning tool applicable to different types of PPPs
      in global health. The matrix arranges transparency and accountability as two
      orthogonal and separate governance dimensions. In the literature, transparency
      and accountability are two of the most commonly discussed dimensions of
      governance but they have not been used in this manner to create a model of
      governance. Transparency is important on its own because it allows learning,
      contributes to accountability, and shapes organizational performance.
      Accountability provides a tool to assure that a PPP is achieving its public
      interest goals and also contributes to improved organizational performance. Both
      contribute to democracy and public perception. The matrix analyzes transparency
      and accountability according to three dimensions (relationships, contents, and
      mechanisms) and assesses the level of each dimension. Using a hypothetical PPP
      example, the article illustrates how the matrix could be used in practice. The
      matrix provides a method to assess the levels of transparency and accountability
      but does not indicate how much of either is good or desirable. The matrix is
      proposed to improve conceptual clarity and help identify concrete options for
      action in planning, assessing, and adjusting PPP governance.

PMID- 30207905
TI  - The Dark Side of Cuba's Health System: Free Speech, Rights of Patients and Labor
      Rights of Physicians.
AB  - This essay questions the achievements and assessments of the Cuban health system.
      It argues that health policies in Cuba in the past half century have been
      implemented with limited concern for civil liberties and certain human rights
      which are considered a core component of a responsive, transparent, and
      accountable health system. Three cases are discussed in support of this
      assessment: 1) the persecution of Cuban analysts who questioned the official
      version of the socio-economic situation of pre-revolutionary Cuba, including the
      health state of affairs; 2) the harassment and segregation of gays and people
      living with HIV; and 3) the violation of labor rights of Cuban physicians working
      in international missions.

PMID- 30207906
TI  - Disseminated Actinomycosis.

PMID- 30207907
TI  - Primary Hyperparathyroidism.

PMID- 30207908
TI  - To Be Guided by Instinct.

PMID- 30207909
TI  - Dry Eye.

PMID- 30207910
TI  - Limiting State Flexibility in Drug Pricing.

PMID- 30207911
TI  - The Tobacco Master Settlement Agreement - Strategic Lessons for Addressing Public
      Health Problems.

PMID- 30207913
TI  - ECMO for Severe Acute Respiratory Distress Syndrome.

PMID- 30207912
TI  - Essential Role of BRCA2 in Ovarian Development and Function.
AB  - The causes of ovarian dysgenesis remain incompletely understood. Two sisters with
      XX ovarian dysgenesis carried compound heterozygous truncating mutations in the
      BRCA2 gene that led to reduced BRCA2 protein levels and an impaired response to
      DNA damage, which resulted in chromosomal breakage and the failure of RAD51 to be
      recruited to double-stranded DNA breaks. The sisters also had microcephaly, and
      one sister was in long-term remission from leukemia, which had been diagnosed
      when she was 5 years old. Drosophila mutants that were null for an orthologue of
      BRCA2 were sterile, and gonadal dysgenesis was present in both sexes. These
      results revealed a new role for BRCA2 and highlight the importance to ovarian
      development of genes that are critical for recombination during meiosis. (Funded
      by the Israel Science Foundation and others.).

PMID- 30207914
TI  - Cyclin-Dependent Kinase 12, Immunity, and Prostate Cancer.

PMID- 30207915
TI  - Lung Cancer with a High Tumor Mutational Burden.

PMID- 30207917
TI  - Pembrolizumab plus Chemotherapy in Lung Cancer.

PMID- 30207918
TI  - Squamous-Cell Carcinoma of the Lung.

PMID- 30207916
TI  - Mutation Clearance after Transplantation for Myelodysplastic Syndrome.
AB  - BACKGROUND: Allogeneic hematopoietic stem-cell transplantation is the only
      curative treatment for patients with myelodysplastic syndrome (MDS). The
      molecular predictors of disease progression after transplantation are unclear.
      METHODS: We sequenced bone marrow and skin samples from 90 adults with MDS who
      underwent allogeneic hematopoietic stem-cell transplantation after a
      myeloablative or reduced-intensity conditioning regimen. We detected mutations
      before transplantation using enhanced exome sequencing, and we evaluated mutation
      clearance by using error-corrected sequencing to genotype mutations in bone
      marrow samples obtained 30 days after transplantation. In this exploratory study,
      we evaluated the association of a mutation detected after transplantation with
      disease progression and survival. RESULTS: Sequencing identified at least one
      validated somatic mutation before transplantation in 86 of 90 patients (96%); 32
      of these patients (37%) had at least one mutation with a maximum variant allele
      frequency of at least 0.5% (equivalent to 1 heterozygous mutant cell in 100
      cells) 30 days after transplantation. Patients with disease progression had
      mutations with a higher maximum variant allele frequency at 30 days than those
      who did not (median maximum variant allele frequency, 0.9% vs. 0%; P<0.001). The
      presence of at least one mutation with a variant allele frequency of at least
      0.5% at day 30 was associated with a higher risk of progression (53.1% vs. 13.0%;
      conditioning regimen-adjusted hazard ratio, 3.86; 95% confidence interval [CI],
      1.96 to 7.62; P<0.001) and a lower 1-year rate of progression-free survival than
      the absence of such a mutation (31.3% vs. 59.3%; conditioning regimen-adjusted
      hazard ratio for progression or death, 2.22; 95% CI, 1.32 to 3.73; P=0.005). The
      rate of progression-free survival was lower among patients who had received a
      reduced-intensity conditioning regimen and had at least one persistent mutation
      with a variant allele frequency of at least 0.5% at day 30 than among patients
      with other combinations of conditioning regimen and mutation status (P<=0.001).
      Multivariate analysis confirmed that patients who had a mutation with a variant
      allele frequency of at least 0.5% detected at day 30 had a higher risk of
      progression (hazard ratio, 4.48; 95% CI, 2.21 to 9.08; P<0.001) and a lower 1
      year rate of progression-free survival than those who did not (hazard ratio for
      progression or death, 2.39; 95% CI, 1.40 to 4.09; P=0.002). CONCLUSIONS: The risk
      of disease progression was higher among patients with MDS in whom persistent
      disease-associated mutations were detected in the bone marrow 30 days after
      transplantation than among those in whom these mutations were not detected.
      (Funded by the Leukemia and Lymphoma Society and others.).

PMID- 30207919
TI  - Aspirin-Exacerbated Respiratory Disease.

PMID- 30207921
TI  - Case 28-2018: A 39-Year-Old Man with Epistaxis, Pain and Erythema of the Forearm,
      and Pancytopenia.

PMID- 30207922
TI  - Therapy in Multiple Sclerosis - Coming of Age.

PMID- 30207923
TI  - Success of Bolus Gastric Feeding After Fundoplication Among Children Who Require
      Preoperative Jejunal Feeding.
AB  - PURPOSE: Management of complicated reflux in infants and children is
      controversial. Jejunal feedings are used when reflux complications occur with
      gastric feeds. We sought to determine how successful fundoplication is to allow
      for return of physiologic gastric feeds in patients requiring jejunal feeds
      preoperatively. METHODS: A retrospective review of patients requiring jejunal
      feeds before fundoplication between 2010 and 2015 was conducted. RESULTS: Two
      hundred thirteen children underwent fundoplication during the study period. One
      hundred fourteen (49%) children required preoperative jejunal feeds. Median
      preoperative jejunal feeding trial was 15 days (interquartile range [IQR] 8-36).
      After fundoplication, gastric feeds were attempted in all patients. Ninety-one
      (80%) patients tolerated feeds postoperatively without return of preoperative
      symptoms. Twenty-one (18%) children developed gastric feeding intolerance and
      were treated with jejunal feeds at a mean of 8 months postoperatively (range 3
      17). Ten (9%) children eventually tolerated intragastric bolus feeds, requiring
      jejunal feeds for a median duration of 2.3 months (IQR 1-5). There were no
      differences seen in those who were able to tolerate gastric early after the
      operation and those who did not. Of the patients who were unable to tolerate
      bolus gastric feeds during the study, a higher proportion had neurologic
      impairment and were on jejunal feeds for a longer period of time before
      fundoplication. CONCLUSION: In the majority of patients requiring continuous
      jejunal feeds to manage complications of reflux, fundoplication allows for
      transition to gastric bolus feeding.

PMID- 30207924
TI  - Developing your communication skills in social work.

PMID- 30207925
TI  - Exploring the use of humour in medical education in the GP small group setting.
AB  - This report summaries work from a dissertation project which critically examines
      the uses of humour in the GP small group learning environment, via a qualitative
      enquiry approach. Humour is widely used in medical education, though conclusions
      from literature are ambiguous and rarely field-focused. The aims of my enquiry
      were to observe the types of humour used and explore the impact these have, with
      a focus on the 'curriculum in action'. I used two data collection methods
      including a group observation as a non-participant and a focus group discussion
      with trainees. Findings support the use of appropriate humour by trainees and
      facilitator to promote learning, including self-depreciating and dark humour. I
      propose that educators should be confident in using humour and brave in exploring
      new humour approaches and modalities, such as medical improvisation and the
      humanities.

PMID- 30207920
TI  - Trial of Fingolimod versus Interferon Beta-1a in Pediatric Multiple Sclerosis.
AB  - BACKGROUND: Treatment of patients younger than 18 years of age with multiple
      sclerosis has not been adequately examined in randomized trials. We compared
      fingolimod with interferon beta-1a in this population. METHODS: In this phase 3
      trial, we randomly assigned patients 10 to 17 years of age with relapsing
      multiple sclerosis in a 1:1 ratio to receive oral fingolimod at a dose of 0.5 mg
      per day (0.25 mg per day for patients with a body weight of <=40 kg) or
      intramuscular interferon beta-1a at a dose of 30 MUg per week for up to 2 years.
      The primary end point was the annualized relapse rate. RESULTS: Of a total of 215
      patients, 107 were assigned to fingolimod and 108 to interferon beta-1a. The mean
      age of the patients was 15.3 years. Among all patients, there was a mean of 2.4
      relapses during the preceding 2 years. The adjusted annualized relapse rate was
      0.12 with fingolimod and 0.67 with interferon beta-1a (absolute difference, 0.55
      relapses; relative difference, 82%; P<0.001). The key secondary end point of the
      annualized rate of new or newly enlarged lesions on T2-weighted magnetic
      resonance imaging (MRI) was 4.39 with fingolimod and 9.27 with interferon beta-1a
      (absolute difference, 4.88 lesions; relative difference, 53%; P<0.001). Adverse
      events, excluding relapses of multiple sclerosis, occurred in 88.8% of patients
      who received fingolimod and 95.3% of those who received interferon beta-1a.
      Serious adverse events occurred in 18 patients (16.8%) in the fingolimod group
      and included seizures (in 4 patients), infection (in 4 patients), and leukopenia
      (in 2 patients). Serious adverse events occurred in 7 patients (6.5%) in the
      interferon beta-1a group and included infection (in 2 patients) and
      supraventricular tachycardia (in 1 patient). CONCLUSIONS: Among pediatric
      patients with relapsing multiple sclerosis, fingolimod was associated with a
      lower rate of relapse and less accumulation of lesions on MRI over a 2-year
      period than interferon beta-1a but was associated with a higher rate of serious
      adverse events. Longer studies are required to determine the durability and
      safety of fingolimod in pediatric multiple sclerosis. (Funded by Novartis Pharma;
      PARADIGMS ClinicalTrials.gov number, NCT01892722 .).

PMID- 30207926
TI  - Case Report of Transmissible Gastroenteritis Coronavirus Infection Associated
      with Small Intestine and Brain Lesions in Piglets.
AB  - This case study report describes a transmissible gastroenteritis coronavirus
      (TGEV) infection presented in a commercial pig herd. The clinical signs of
      infection appeared in newborn piglets, including medium morbidity and low
      mortality rates. Rectal swabs were collected from five different affected litters
      for laboratory examinations. Samples from two dead piglets and two euthanized
      affected piglets were collected for gross and histopathological examinations. All
      fecal samples were tested TGEV positive by real-time polymerase chain reaction
      (RT-PCR). Necropsy revealed nonspecific gross lesions. The histopathological
      examinations revealed villi fused with denuded tips and severe villus atrophy,
      leading to extensive epithelial flattening in middle and lower small intestine.
      The architecture pattern of villi presented columnar and cuboidal poorly
      differentiated enterocytes with mild subepithelial edema. In some enterocytes,
      pycnotic nuclei were detected. Microscopic examination of brain tissue revealed
      diffuse gliosis in the area of pia matter with mild congestion of the meningeal
      and parenchymal vessels and neuronal degeneration. In conclusion, this case study
      reported an epidemic TGEV infection in piglets, characterized by low mortality
      and medium morbidity rates accompanied by typical histopathological lesions in
      small intestine, as well as by coexisting brain lesions, that are described for
      the first time.

PMID- 30207927
TI  - Development and Evaluation of a User-Centered Mobile Telestroke Platform.
AB  - BACKGROUND: Reperfusion is the most effective acute treatment for ischemic stroke
      within a narrow therapeutic time window. Ambulance-based telestroke is a novel
      way to improve stroke diagnosis and timeliness of treatment. This study aims to
      (1) assess the usability of our ambulance-based telestroke platform and (2)
      identify strengths and limitations of the system from the user's perspective.
      MATERIALS AND METHODS: An ambulance was equipped with a mobile telemedicine
      system to perform remote stroke assessments. Scripted scenarios were performed by
      actors during transport and evaluated by physicians using the National Institutes
      of Health Stroke Scale (NIHSS). Scores obtained during transport were compared
      with original scripted NIHSS scores. Participants completed the System Usability
      Scale (SUS), NASA Task Load Index (NASA TLX), audio/video quality scale, and a
      modified Acceptability of Technology survey to assess perceptions and usability.
      In addition, interviews were conducted to evaluate user's experience. Descriptive
      analysis was used for all surveys. Weighted kappa statistics was used to compare
      the agreement in NIHSS scores. RESULTS: Ninety-one percent (59/65) of mobile
      scenarios were completed. Median completion time was 9 min (range 4-17 min).
      There was moderate inter-rater agreement (weighted kappa = 0.46 [95% confidence
      interval 0.33-0.60, p = 0.0018]) among mobile and original scripted scenarios.
      The mean SUS score was 68.8 (standard deviation = 15.9). There was variability
      between usability score and formative feedback among all end-users in the areas
      of usability issues (i.e., audibility and equipment stability) and safety.
      CONCLUSION: Before implementation of a mobile prehospital telestroke program, the
      use of combined clinical simulation and Plan-Do-Study-Act methodology can improve
      the quality and optimization of the telemedicine system.

PMID- 30207929
TI  - Development of a new method for biomonitoring of multiple metals in occupational
      exposure.
AB  - The assessment of co-exposure to several types of metal contamination poses a
      hurdle for occupational monitoring. Determination of elements in biological
      samples is an important way to evaluate occupational exposure. However, optimized
      methods for the extraction of multiple metals from biological samples have not
      been reported in recent studies. Therefore, solid-phase extraction (SPE) based on
      the functionalized Nano-zeolite Y was suggested for the biomonitoring of metal co
      exposure. SPE was conducted with ammonium pyrrolidine dithiocarbamate (APDC)
      surrounded by Triton X-100 micelles, which were loaded into the pores of Nano
      zeolite Y. In this study, SPE was optimized for pre-concentration of trace
      amounts of chromium (Cr), cadmium (Cd), and lead (Pb) in urine samples with
      respect to the pH, APDC concentration, elution condition, amount of
      functionalized Nano-zeolite Y, and sample volume. This method has been
      successfully optimized for the extraction of the mentioned multiple metals with
      >97% efficiency and an acceptable reproducibility with a coefficient variation of
      <10%. This method could be used in the extraction of multiple metals in
      environmental and occupational exposure conditions. In this study, urine samples
      of welding workers were evaluated following this optimized method.

PMID- 30207930
TI  - The relationship between brain microbleeds and homeostatic markers in the
      treatment of ischemic stroke.
AB  - OBJECTIVES: There is no definitive data regarding the usefulness of Brain
      microbleeds (BMBs) as an imaging marker with homeostatic markers to predict
      intracerebral hemorrhage (ICH) and ischemic stroke risk to personalize decisions
      on anticoagulation in AF. In this study, we prospectively evaluated clinical,
      radiological homeostatic biomarkers and their association with stroke outcomes in
      73 AF-related ischemic stroke patients. METHODS: All BMBs were measured manually
      on Susceptibility-Weighted Imaging (SWI). The levels of NT-pro-BNP, hs-CRP, FVII,
      FVIII and vWF were studied as homeostatic markers. For all patients, we
      calculated CHADS2, CHA2DS2-VASc, HAS-BLED scores and modified Rankin Scale (mRS)
      scores. Functional independence and good clinical outcome were defined as a mRS
      score of 0-2. RESULTS: The mean age of the study population was 69.74 +/- 9.79
      years, and 36 patients were female. The leading vascular risk factor was
      hypertension (61%). BMBs were determined in 20 patients (27.4%) on SWI, 12
      patients had less than five lesions. Presence of BMBs lesions on SWI was
      significantly associated with age and hypertension (p = .020) and congestive
      heart failure (p = .011). The median CHA2DS2-VASc score in patients was 4.96 +/-
      1.54. CHA2DS2-VASc score (p = .042), CHADS2 score (p = .037) and HAS- BLED score
      (p = .033) were significantly related with the presence of BMBs in the study
      patients. Among homeostatic markers, the levels of NT-pro-BNP, hs-CRP, and vWF
      were significantly associated with the presence of microbleeds (p = .013, p =
      .029, p = .020, respectively). CONCLUSION: Pathogenesis of AF is involved
      abnormal changes of hemostasis, endothelial dysfunction, antithrombotic state and
      inflammation. The homeostatic markers, which play role in these pathways, and the
      presence of BMBs could use to form a prognostic clinic assessment tool to predict
      bleeding risk.

PMID- 30207931
TI  - CT Findings of Acute Small-Bowel Entities.
AB  - Although a broad spectrum of entities can induce acute pathologic changes in the
      small bowel, there are relatively few imaging features that are characteristic of
      a specific diagnosis on the basis of CT findings. Specific clinical information,
      including time course and onset of disease, patient risk factors, and any recent
      pharmacologic or radiation therapy, is often instrumental in refining the
      differential diagnosis. A wide spectrum of disorders is reviewed in this article;
      however, given the breadth of disorders associated with the small bowel,
      neoplastic and infectious conditions affecting the small bowel that can manifest
      acutely are not specifically discussed. Vascular diseases that can affect the
      small bowel regionally or diffusely, including thromboembolic and hypoperfusion
      phenomena, as well as a spectrum of vasculitides, are reviewed. Iatrogenic causes
      of small bowel disorders are discussed, including angiotensin-converting enzyme
      inhibitor-induced angioedema, and chemotherapy- and radiation therapy-associated
      patterns of disease. Autoimmune and hereditary conditions that can affect the
      small bowel, including systemic lupus erythematosus and genetic C1 esterase
      inhibitor deficiency, respectively, are reviewed. (c)RSNA, 2018.

PMID- 30207932
TI  - Imaging and Surgical Management of Anorectal Vaginal Fistulas.
AB  - Anorectal vaginal fistulas (ARVFs) can result in substantial morbidity and
      potentially embarrassing symptoms in adult women of all ages. Despite having what
      may be obvious clinical manifestations, the fistulas themselves can be difficult
      to identify with imaging. MRI is the modality of choice for the diagnosis and
      characterization of ARVFs. A dedicated protocol involving the use of vaginal gel
      and optimized imaging planes with respect to the vagina, as well as an
      understanding of the MRI pelvic floor anatomy, is crucial for reporting
      surgically relevant details. Ancillary findings such as postsurgical changes,
      inflammation, abscess, sphincter destruction, and neoplasm are well evaluated.
      Vaginography, contrast enema, endoscopic US, and CT can be highly useful
      complementary diagnostic examinations. The entities that result in ARVFs may be
      obstetric, inflammatory (eg, Crohn disease and diverticulitis), neoplastic,
      iatrogenic, and/or radiation induced. Surgical management is heavily dependent on
      the cause and complexity of the fistulizing disease, which are related to the
      location of the fistula in the vagina, the type and extent of fistula branching,
      the number of fistulas, sphincter tears, inflammation, and abscess. (c)RSNA,
      2018.

PMID- 30207934
TI  - Congratulations to the 2018 Editorial Fellows.

PMID- 30207933
TI  - MR Neurographic Evaluation of Facial and Neck Pain: Normal and Abnormal
      Craniospinal Nerves below the Skull Base.
AB  - Cranial nerve disease outside the skull base is a common cause of facial and/or
      neck pain, which causes significant disability for patients and frustration for
      clinicians. Neuropathy in this region can be traumatic, idiopathic, or iatrogenic
      secondary to dental and surgical procedures. MR neurography is a modification of
      conventional MRI techniques dedicated to evaluation of peripheral nerves and is
      being increasingly used for imaging of peripheral neuropathies at various sites
      in the body. MR neurography facilitates assessment of different causes of
      craniofacial pain and cranial nerves and allows elegant depiction of a multitude
      of regional neuropathies. This article discusses the anatomy, pathologic
      conditions, and imaging findings of the commonly implicated but difficult to
      image infratentorial nerves, such as the peripheral trigeminal nerve and its
      branches, facial nerve, glossopharyngeal nerve, vagus nerve, hypoglossal nerve,
      and greater and lesser occipital nerves. (c)RSNA, 2018.

PMID- 30207935
TI  - Updated Fleischner Society Guidelines for Managing Incidental Pulmonary Nodules:
      Common Questions and Challenging Scenarios.
AB  - The new guidelines for managing incidental pulmonary nodules published by the
      Fleischner Society in 2017 reflect an improved understanding of the risk factors
      and biologic features of lung cancer. Specific topics emphasized in the updated
      guidelines include a new threshold size for follow-up, the importance of the
      morphologic features of nodules, accurate nodule measurements, recognition of
      subsolid components, understanding interval growth or change in nodule
      morphology, and knowledge of patient risk factors. The updated guidelines enable
      greater personal flexibility in the decision-making process and encourage
      individualized management of pulmonary nodules. These factors may introduce new
      challenges for radiologists, who previously used solely nodule size to make
      management recommendations. The authors describe eight scenarios that illustrate
      the challenges potentially encountered when applying the new guidelines to
      pulmonary nodule management. (c)RSNA, 2018.

PMID- 30207936
TI  - Retroperitoneal Leiomyosarcoma From the Radiologic Pathology Archives.
AB  - Leiomyosarcoma is a malignant neoplasm that shows smooth muscle differentiation.
      It is the second most common sarcoma to affect the retroperitoneum.
      Retroperitoneal leiomyosarcomas may grow to large sizes before detection and may
      be an incidental finding at imaging. When symptomatic, retroperitoneal
      leiomyosarcoma may cause compressive symptoms, including pain. Retroperitoneal
      leiomyosarcoma most commonly manifests as a large soft-tissue mass, with areas of
      necrosis. The most frequent pattern of growth is an entirely extravascular mass.
      Less commonly, leiomyosarcoma may demonstrate both extravascular and
      intravascular components. Rarely, retroperitoneal leiomyosarcomas are completely
      intravascular, typically arising from the inferior vena cava. Given its variable
      imaging features, a large variety of neoplastic and nonneoplastic conditions are
      included in the differential diagnosis of retroperitoneal leiomyosarcoma. In this
      review, the authors discuss retroperitoneal leiomyosarcoma, with emphasis on the
      pathologic basis of disease, and illustrate the multimodality imaging appearances
      of retroperitoneal leiomyosarcoma using cases from the Radiologic Pathology
      Archives of the American Institute for Radiologic Pathology. The authors review
      important differential considerations of retroperitoneal leiomyosarcoma, focusing
      on the extravascular pattern of growth, and emphasize clinical and imaging
      features that help radiologists differentiate leiomyosarcoma from the most
      frequent mimics. The information presented in this review will aid radiologists
      in fulfilling their key roles in the diagnosis, operative planning, and follow-up
      of patients with retroperitoneal leiomyosarcoma.

PMID- 30207937
TI  - Spinal Hematomas: What a Radiologist Needs to Know.
AB  - Spinal hematomas are a frequent indication for radiologic evaluation and can be a
      diagnostic dilemma for many radiologists and surgeons. There are four types of
      spinal hematomas: epidural, subdural, subarachnoid, and intramedullary (spinal
      cord) hematomas. Because they differ by their location in relationship to the
      meningeal membranes and spinal cord, unique radiologic appearances can be
      recognized to distinguish these types of spinal hemorrhage. Anatomic knowledge of
      the spinal compartments is essential to the radiologist for confident imaging
      diagnosis of spinal hematomas and to specify correct locations. MRI is the
      modality of choice to diagnose the location of the hematoma, characterize
      important features such as age of the hemorrhage, and detect associated injury or
      disease. Each type of spinal hematoma has imaging patterns and characteristics
      that distinguish it from the others, as these specific spinal compartments
      displace and affect the adjacent anatomic structures. Early detection and
      accurate localization of spinal hematomas is critical for the surgeon to address
      the proper treatment and surgical decompression, when necessary, as neurologic
      deficits may otherwise become permanent. Online supplemental material is
      available for this article. (c)RSNA, 2018.

PMID- 30207938
TI  - Growth Patterns of Retroperitoneal Leiomyosarcomas.

PMID- 30207939
TI  - Invited Commentary on "MR Neurographic Evaluation of Facial and Neck Pain".

PMID- 30207940
TI  - Mechanisms of Uptake of Common Radiopharmaceuticals RadioGraphics Fundamentals |
      Online Presentation.

PMID- 30207941
TI  - Invited Commentary on "Radiation Dose Reduction in Pediatric CT," with Response
      from Dr Nagayama et al.

PMID- 30207942
TI  - Invited Commentary on "Updated Fleischner Society Guidelines for Managing
      Incidental Pulmonary Nodules".

PMID- 30207944
TI  - Radiographic Review of Avulsion Fractures RadioGraphics Fundamentals | Online
      Presentation.

PMID- 30207943
TI  - Radiation Dose Reduction at Pediatric CT: Use of Low Tube Voltage and Iterative
      Reconstruction.
AB  - Given the growing awareness of and concern for potential carcinogenic effects of
      exposure of children to ionizing radiation at CT, optimizing acquisition
      parameters is crucial to achieve diagnostically acceptable image quality at the
      lowest possible radiation dose. Among currently available dose reduction
      techniques, recent technical innovations have allowed the implementation of low
      tube voltage scans and iterative reconstruction (IR) techniques into daily
      clinical practice for pediatric CT. The benefits of lowering tube voltage include
      a considerable reduction in radiation dose and improved contrast on images,
      especially when an iodinated contrast medium is used. The increase in noise,
      which is attributed to decreased photon penetration, is a major drawback but is
      not as severe as that at adult CT because of the small body size of children. In
      addition, use of IR algorithms can suppress increased noise, yielding wider
      applicability for low tube voltage scans. However, a careful implementation
      strategy and methodologic approach are necessary to maximize the potential for
      dose reduction while preserving diagnostic image quality under each clinical
      condition. The potential pitfalls of and topics related to these techniques
      include (a) the effect of tube voltage on the surface radiation dose, (b) the
      effect of window settings, (c) accentuation of metallic artifacts, (d)
      deterioration of low contrast detectability at low-dose settings, (e)
      interscanner variation of x-ray spectra, and (f) a comparison with the use of a
      spectral shaping technique. Appropriate use of low tube voltage and IR techniques
      is helpful for radiation dose reduction in most applications of pediatric CT.
      Online DICOM image stacks are available for this article . (c)RSNA, 2018.

PMID- 30207945
TI  - Adenomyosis: A Sonographic Diagnosis.
AB  - Adenomyosis is a common benign uterine condition and a frequent cause of pelvic
      pain in premenopausal women. Transvaginal US is now considered the primary
      imaging modality for the diagnosis of adenomyosis, and thus radiologists should
      be familiar with its sonographic appearance. US findings can be divided into
      three categories, which parallel the histology of adenomyosis: (a) ectopic
      endometrial glands and stroma, (b) muscular hyperplasia/hypertrophy, and (c)
      increased vascularity. Ectopic endometrial glands manifest as echogenic nodules
      and striations, radiating from the endometrium into the myometrium. When the
      glands contain fluid, myometrial cysts and fluid-filled striations may be visible
      at US. Muscular hyperplasia and hypertrophy cause focal or diffuse myometrial
      thickening and globular uterine enlargement, often with thin "venetian blind"
      shadows. The combination of these findings results in a heterogeneous myometrium,
      with blurring of the endometrial border. Adenomyosis increases uterine
      vascularity, depicted as a pattern of penetrating vessels at color Doppler US.
      Other US techniques that are helpful in the diagnosis of adenomyosis include
      obtaining cine clips and coronal reformatted images, both of which can survey the
      entire endometrial-myometrial border, and performing saline-infusion
      sonohysterography, during which ectopic glands frequently fill with either air or
      fluid. While most cases of adenomyosis develop spontaneously, there are specific
      inciting causes that include tamoxifen use, postendometrial ablation syndrome,
      and deep-infiltrating endometriosis. Mimics of adenomyosis include leiomyomas,
      uterine contractions, neoplasms, and vascular malformations. This article reviews
      the pathophysiology of adenomyosis and correlates it with the US findings,
      highlights specific causes of adenomyosis, and describes how to distinguish this
      common diagnosis from a variety of mimics. Online supplemental material is
      available for this article. (c)RSNA, 2018.

PMID- 30207946
TI  - Suture Breakage Warning System for Robotic Surgery.
AB  - As robotic surgery has increased in popularity, the lack of haptic feedback has
      become a growing issue due to the application of excessive forces that may lead
      to clinical problems such as intraoperative and postoperative suture breakage.
      Previous suture breakage warning systems have largely depended on visual and/or
      auditory feedback modalities, which have been shown to increase cognitive load
      and reduce operator performance. This work catalogues a new sensing technology
      and haptic feedback system (HFS) that can reduce instances of suture failure
      without negatively impacting performance outcomes including knot quality. Suture
      breakage is common in knot-tying as the pulling motion introduces prominent shear
      forces. A shear sensor mountable on the da Vinci robotic surgical system's
      Cadiere grasper detects forces that correlate to the suture's internal tension.
      HFS then provides vibration feedback to the operator as forces near a particular
      material's failure load. To validate the system, subjects tightened a total of
      four knots, two with the Haptic Feedback System (HFS) and two without feedback.
      The number of suture breakages were recorded and knot fidelity was evaluated by
      measuring knot slippage. Results showed that instances of suture failure were
      significantly reduced when HFS was enabled (p = 0.0078). Notably, knots tied with
      HFS also showed improved quality compared to those tied without feedback (p =
      0.010). The results highlight the value of HFS in improving robotic procedure
      outcomes by reducing instances of suture failures, producing better knots, and
      reducing the need for corrective measures.

PMID- 30207947
TI  - Fusion of Medical Sensors Using Adaptive Cloud Model in Local Laplacian Pyramid
      Domain.
AB  - Detail information on objects of interest plays a vital role in current medical
      diagnosis. However, the existing multimodal sensor fusion methods cause problems
      of low contrast and color distortion during the process of integration.
      Therefore, the preservation of detail information in high contrast is worthy of
      investment in the field of medical image fusion. This paper presents a new
      multiscale fusion-based framework using the local Laplacian pyramid transform
      (LLP) and adaptive cloud model (ACM). The proposed framework, LLP+ACM, includes
      three key modules. First, the input images are decomposed into detailenhanced
      approximate and residual images using LLP. Second, ACMis adopted to fuse the
      approximate images. A salience match tool is used to fuse the residual images.
      Third, the fused image is reconstructed using the inversed LLP. Experiments show
      that the proposed LLP+ACM significantly improves detail information with high
      contrast and reduces the color distortion of the fused images in both subjective
      and objective evaluations.

PMID- 30207948
TI  - Anthropomorphic features for On-line Signatures.
AB  - Many features have been proposed in on-line signature verification. Generally,
      these features rely on the position of the on-line signature samples and their
      dynamic properties, as recorded by a tablet. This paper proposes a novel feature
      space to describe efficiently on-line signatures. Since producing a signature
      requires a skeletal arm system and its associated muscles, the new feature space
      is based on characterizing the movement of the shoulder, the elbow and the wrist
      joints when signing. As this motion is not directly obtained from a digital
      tablet, the new features are calculated by means of a virtual skeletal arm (VSA)
      model, which simulates the architecture of a real arm and forearm. Specifically,
      the VSA motion is described by its 3D joint position and its joint angles. These
      anthropomorphic features are worked out from both pen position and orientation
      through the VSA forward and direct kinematic model. The anthropomorphic features'
      robustness is proved by achieving state-of-the-art performance with several
      verifiers and multiple benchmarks on third party signature databases, which were
      collected with different devices and in different languages and scripts.

PMID- 30207949
TI  - Estimating the Number of Correct Matches Using Only Spatial Order.
AB  - Correctly matching feature points in a pair of images is an important
      preprocessing step for many computer vision applications. In this paper we
      propose an efficient method for estimating the number of correct matches without
      explicitly computing them. To this end, we propose to analyze the set of matches
      using the spatial order of the features, as projected to the x-axis of the image.
      The set of features in each image is thus represented by a sequence, and analyzed
      using the Kendall and Spearman Footrule distance metrics between permutations.
      This result is interesting in its own right. Moreover, we demonstrate three
      useful applications of our method: (i) a new halting condition for RANSAC based
      epipolar geometry estimation methods, (ii) discarding spatially unrelated image
      pairs in the Structure-from-Motion pipeline, and (iii) computing the probability
      that a given match is correct based on the rank of the features within the
      sequences. Our experiments on a large number of synthetic and real data
      demonstrate the effectiveness of our method. For example, the running time of the
      image matching stage in the Structure-from-Motion pipeline may be reduced by
      about 90% while preserving about 85% of the image pairs with spatial overlap.

PMID- 30207950
TI  - Multivariate mixture model for myocardial segmentation combining multi-source
      images.
AB  - The author proposes a method for simultaneous registration and segmentation of
      multi-source images, using the multivariate mixture model (MvMM) and maximum of
      log-likelihood (LL) framework. Specifically, the method is applied to the
      myocardial segmentation combining the complementary information from multi
      sequence (MS) cardiac magnetic resonance (CMR) images. For the image misalignment
      and incongruent data, the MvMM is formulated with transformations and is further
      generalized for dealing with the hetero-coverage multi-modality images (HC-MMIs).
      The segmentation of MvMM is performed in a virtual common space, to which all the
      images and misaligned slices are simultaneously registered. Furthermore, this
      common space can be divided into a number of sub-regions, each of which contains
      congruent data, thus the HC-MMIs can be modeled using a set of conventional
      MvMMs. Results show that MvMM obtained significantly better performance compared
      to the conventional approaches and demonstrated good potential for scar
      quantification as well as myocardial segmentation. The generalized MvMM has also
      demonstrated better robustness in the incongruent data, where some images may not
      fully cover the region of interest, and the full coverage can only be
      reconstructed combining the images from multiple sources.

PMID- 30207951
TI  - Improved photoacoustic-based oxygen saturation estimation with SNR-regularized
      local fluence correction.
AB  - As photoacoustic (PA) imaging makes its way into the clinic, accuracy of PA-based
      metrics becomes increasingly important. To address this need, a method combining
      finite-element-based local fluence correction (LFC) with signal-to-noise-ratio
      (SNR) regularization was developed and validated to accurately estimate oxygen
      saturation (SO2) in tissue. With data from a Vevo LAZR system, performance of our
      LFC approach was assessed in ex vivo blood targets (37.6% - 99.6% SO2) and in
      vivo rat arteries. Estimation error of absolute SO2 and change in SO2 reduced
      from 10.1% and 6.4%, respectively, without LFC to 2.8% and 2.0%, respectively,
      with LFC, while accuracy of the LFC method was correlated with the number of
      wavelengths acquired. This work demonstrates the need for SNR-regularized LFC to
      accurately quantify SO2 with PA imaging.

PMID- 30207952
TI  - Ultimate limits of differential resonant MEMS sensors based on two coupled linear
      resonators.
AB  - In this paper, we investigate how additive noise, e.g. thermomechanical noise,
      impacts the resolution of mode-localized resonant sensing architectures based on
      two passively-coupled linear resonators. Existing work suggests that the ultimate
      resolution of these sensors can be improved by decreasing the coupling
      coefficient of the resonators. The present work gives an analytical proof that
      this result does not hold, and that the resolution of such sensors is actually
      independent of the coupling strength. These results are established for different
      output metrics and operating points, in closed-loop and in open-loop, and
      compared to those obtained with other approaches based on actively-coupled
      resonators.

PMID- 30207953
TI  - Real-Time High-Frame-Rate Cardiac B-Mode and Tissue Doppler Imaging Based on
      Multiline Transmission and Multiline Acquisition.
AB  - Cardiovascular diseases, the leading cause of death in the world, are often
      associated with the dysfunction of the left ventricle. Even if, in clinical
      practice, the myocardial function is often assessed through visual wall motion
      scoring on B-mode images, quantitative techniques have been introduced, e.g.,
      ultrasound tissue Doppler imaging (TDI). However, this technique suffers from the
      limited frame rate of currently available imaging techniques that needs to be
      balanced with the field of view. High-frame-rate (HFR) cardiac imaging has been
      recently tested off-line by simultaneously transmitting multiple focused beams
      into different directions and acquiring raw channel data into a PC. Several image
      lines were then reconstructed from the echoes of each transmission (TX) event.
      The same approach has been used to increase the TDI frame rate without
      restricting the field of view. This paper demonstrates the real-time feasibility
      of multiline TX and acquisition methods for both HFR cardiac B-mode and TDI.
      These approaches have been implemented on the ULA-OP 256 research scanner, by
      taking care that the related resources were optimally exploited for these new
      applications. The obtainable performance in terms of image quality and frame rate
      has also been investigated. Experiments performed with a 128-element phased array
      probe show, for the first time, that real-time B-mode imaging is feasible at up
      to 1150 Hz without significant reduction in image quality or field of view. The
      implementation of a real-time TDI algorithm allowed obtaining TDI images with a
      frame rate of 288 Hz for a 90 degrees -wide field of view. Finally, in vivo
      examples demonstrate the feasibility and the suitability of the method in
      clinical studies.

PMID- 30207954
TI  - Persistence Atlas for Critical Point Variability in Ensembles.
AB  - This paper presents a new approach for the visualization and analysis of the
      spatial variability of features of interest represented by critical points in
      ensemble data. Our framework, called Persistence Atlas, enables the visualization
      of the dominant spatial patterns of critical points, along with statistics
      regarding their occurrence in the ensemble. The persistence atlas represents in
      the geometrical domain each dominant pattern in the form of a confidence map for
      the appearance of critical points. As a by-product, our method also provides 2
      dimensional layouts of the entire ensemble, highlighting the main trends at a
      global level. Our approach is based on the new notion of Persistence Map, a
      measure of the geometrical density in critical points which leverages the
      robustness to noise of topological persistence to better emphasize salient
      features. We show how to leverage spectral embedding to represent the ensemble
      members as points in a low-dimensional Euclidean space, where distances between
      points measure the dissimilarities between critical point layouts and where
      statistical tasks, such as clustering, can be easily carried out. Further, we
      show how the notion of mandatory critical point can be leveraged to evaluate for
      each cluster confidence regions for the appearance of critical points. Most of
      the steps of this framework can be trivially parallelized and we show how to
      efficiently implement them. Extensive experiments demonstrate the relevance of
      our approach. The accuracy of the confidence regions provided by the persistence
      atlas is quantitatively evaluated and compared to a baseline strategy using an
      off-the-shelf clustering approach. We illustrate the importance of the
      persistence atlas in a variety of real-life datasets, where clear trends in
      feature layouts are identified and analyzed. We provide a lightweight VTK-based
      C++ implementation of our approach that can be used for reproduction purposes.

PMID- 30207955
TI  - Visualization of Large Molecular Trajectories.
AB  - The analysis of protein-ligand interactions is a time-intensive task. Researchers
      have to analyze multiple physico-chemical properties of the protein at once and
      combine them to derive conclusions about the protein-ligand interplay. Typically,
      several charts are inspected, and 3D animations can be played side-by-side to
      obtain a deeper understanding of the data. With the advances in simulation
      techniques, larger and larger datasets are available, with up to hundreds of
      thousands of steps. Unfortunately, such large trajectories are very difficult to
      investigate with traditional approaches. Therefore, the need for special tools
      that facilitate inspection of these large trajectories becomes substantial. In
      this paper, we present a novel system for visual exploration of very large
      trajectories in an interactive and user-friendly way. Several visualization
      motifs are automatically derived from the data to give the user the information
      about interactions between protein and ligand. Our system offers specialized
      widgets to ease and accelerate data inspection and navigation to interesting
      parts of the simulation. The system is suitable also for simulations where
      multiple ligands are involved. We have tested the usefulness of our tool on a set
      of datasets obtained from protein engineers, and we describe the expert feedback.

PMID- 30207956
TI  - In Pursuit of Error: A Survey of Uncertainty Visualization Evaluation.
AB  - Understanding and accounting for uncertainty is critical to effectively reasoning
      about visualized data. However, evaluating the impact of an uncertainty
      visualization is complex due to the difficulties that people have interpreting
      uncertainty and the challenge of defining correct behavior with uncertainty
      information. Currently, evaluators of uncertainty visualization must rely on
      general purpose visualization evaluation frameworks which can be ill-equipped to
      provide guidance with the unique difficulties of assessing judgments under
      uncertainty. To help evaluators navigate these complexities, we present a
      taxonomy for characterizing decisions made in designing an evaluation of an
      uncertainty visualization. Our taxonomy differentiates six levels of decisions
      that comprise an uncertainty visualization evaluation: the behavioral targets of
      the study, expected effects from an uncertainty visualization, evaluation goals,
      measures, elicitation techniques, and analysis approaches. Applying our taxonomy
      to 86 user studies of uncertainty visualizations, we find that existing
      evaluation practice, particularly in visualization research, focuses on
      Performance and Satisfaction-based measures that assume more predictable and
      statistically-driven judgment behavior than is suggested by research on human
      judgment and decision making. We reflect on common themes in evaluation practice
      concerning the interpretation and semantics of uncertainty, the use of confidence
      reporting, and a bias toward evaluating performance as accuracy rather than
      decision quality. We conclude with a concrete set of recommendations for
      evaluators designed to reduce the mismatch between the conceptualization of
      uncertainty in visualization versus other fields.

PMID- 30207957
TI  - Towards Fully Mobile 3D Face, Body, and Environment Capture Using Only Head-worn
      Cameras.
AB  - We propose a new approach for 3D reconstruction of dynamic indoor and outdoor
      scenes in everyday environments, leveraging only cameras worn by a user. This
      approach allows 3D reconstruction of experiences at any location and virtual
      tours from anywhere. The key innovation of the proposed ego-centric
      reconstruction system is to capture the wearer's body pose and facial expression
      from near-body views, e.g. cameras on the user's glasses, and to capture the
      surrounding environment using outward-facing views. The main challenge of the ego
      centric reconstruction, however, is the poor coverage of the near-body views -
      that is, the user's body and face are observed from vantage points that are
      convenient for wear but inconvenient for capture. To overcome these challenges,
      we propose a parametric-model-based approach to user motion estimation. This
      approach utilizes convolutional neural networks (CNNs) for near-view body pose
      estimation, and we introduce a CNN-based approach for facial expression
      estimation that combines audio and video. For each time-point during capture, the
      intermediate model-based reconstructions from these systems are used to re-target
      a high-fidelity pre-scanned model of the user. We demonstrate that the proposed
      self-sufficient, head-worn capture system is capable of reconstructing the
      wearer's movements and their surrounding environment in both indoor and outdoor
      situations without any additional views. As a proof of concept, we show how the
      resulting 3D-plus-time reconstruction can be immersively experienced within a
      virtual reality system (e.g., the HTC Vive). We expect that the size of the
      proposed egocentric capture-and-reconstruction system will eventually be reduced
      to fit within future AR glasses, and will be widely useful for immersive 3D
      telepresence, virtual tours, and general use-anywhere 3D content creation.

PMID- 30207958
TI  - FocusAR: Auto-focus Augmented Reality Eyeglasses for both Real World and Virtual
      Imagery.
AB  - We describe a system which corrects dynamically for the focus of the real world
      surrounding the near-eye display of the user and simultaneously the internal
      display for augmented synthetic imagery, with an aim of completely replacing the
      user prescription eyeglasses. The ability to adjust focus for both real and
      virtual stimuli will be useful for a wide variety of users, but especially for
      users over 40 years of age who have limited accommodation range. Our proposed
      solution employs a tunable-focus lens for dynamic prescription vision correction,
      and a varifocal internal display for setting the virtual imagery at appropriate
      spatially registered depths. We also demonstrate a proof of concept prototype to
      verify our design and discuss the challenges to building an auto-focus augmented
      reality eyeglasses for both real and virtual.

PMID- 30207959
TI  - ARbis Pictus: A Study of Vocabulary Learning with Augmented Reality.
AB  - We conducted a fundamental user study to assess potential benefits of AR
      technology for immersive vocabulary learning. With the idea that AR systems will
      soon be able to label real-world objects in any language in real time, our within
      subjects lab-based study explores the effect of such an AR vocabulary prompter on
      participants learning nouns in an unfamiliar foreign language, compared to a
      traditional flashcard-based learning approach. Our results show that the
      immersive AR experience of learning with virtual labels on real-world objects is
      both more effective and more enjoyable for the majority of participants, compared
      to flashcards. Specifically, when participants learned through augmented reality,
      they scored significantly better on both same-day and 4-day delayed productive
      recall tests than when they learned using the flashcard method. We believe this
      result is an indication of the strong potential for language learning in
      augmented reality, particularly because of the improvement shown in sustained
      recall compared to the traditional approach.

PMID- 30207960
TI  - An Extended Depth-at-Field Volumetric Near-Eye Augmented Reality Display.
AB  - We introduce an optical design and a rendering pipeline for a full-color
      volumetric near-eye display which simultaneously presents imagery with near
      accurate per-pixel focus across an extended volume ranging from 15cm (6.7
      diopters) to 4M (0.25 diopters), allowing the viewer to accommodate freely across
      this entire depth range. This is achieved using a focus-tunable lens that
      continuously sweeps a sequence of 280 synchronized binary images from a high
      speed, Digital Micromirror Device (DMD) projector and a high-speed, high dynamic
      range (HDR) light source that illuminates the DMD images with a distinct color
      and brightness at each binary frame. Our rendering pipeline converts 3-D scene
      information into a 2-D surface of color voxels, which are decomposed into 280
      binary images in a voxel-oriented manner, such that 280 distinct depth positions
      for full-color voxels can be displayed.

PMID- 30207961
TI  - Intrinsic Image Decomposition with Step and Drift Shading Separation.
AB  - Decomposing an image into the shading and reflectance layers remains challenging
      due to its severely under-constrained nature. We present an approach based on
      illumination decomposition that recovers the intrinsic images without additional
      information, e.g., depth or user interaction. Our approach is based on the
      rationale that the shading component contains the step and drift channels
      simultaneously. We decompose the illumination into two channels: the step
      shading, corresponding to the sharp shading changes due to cast shadow or abrupt
      shape changes; the drift shading, accounting for the smooth shading variations
      due to gradual illumination changes or slow shape changes. Due to such
      transformation of turning the conventional assumption that shading has smoothness
      as reasonable prior, our model has the advantages in handling real images,
      especially with the cast shadows or strong shape edges. We also apply a much
      stricter edge classifier along with a reinforcement process to enhance our
      method. We formulate the problem using a two-parameter energy function and split
      it into two energy functions corresponding to the reflectance and step shading.
      Experiments on the MIT dataset, the IIW dataset and the MPI Sintel dataset have
      shown the success of our approach over the state-of-the-art methods.

PMID- 30207962
TI  - Counteracting the Slowdown of Reaction Times in a Vigilance Experiment With 40-Hz
      Transcranial Alternating Current Stimulation.
AB  - Indicators for a decrement in vigilance are a slowdown in reaction times and an
      increase in alpha power in the electroencephalogram in posterior regions of the
      brain. Transcranial alternating current stimulation (tACS) is a
      neuropsychological technique that has been found to interact with intrinsic brain
      oscillations and is able to enhance cognitive and behavioral performance. Recent
      studies show that tACS in the gamma frequency range (30-80 Hz) is able to
      downregulate amplitudes in the alpha frequency range (8-12 Hz), in accordance to
      the effect referred to as cross-frequency coupling, where intrinsic alpha and
      gamma waves modulate each other. We applied 40 Hz gamma-tACS to the visual cortex
      during a vigilance experiment and investigated if stimulation improves reaction
      times and error rates with time-on-task. In our sham controlled experiment,
      participants completed two blocks of 30 minutes duration while performing the
      same visual two-choice task. The first block was used as BASELINE. A statistical
      analysis with a linear mixed model revealed a significantly lower increase of
      modeled reaction times over time in the INTERVENTION-block of the tACS-group as
      compared with their BASELINE-block whereas there was no significant change
      between the BASELINE- and INTERVENTION-block for the SHAM-group. Error rates did
      not differ between groups. This paper indicates that gamma-tACS can enhance
      performance in vigilance tasks as it significantly decreased the slowdown of
      reaction times in our study.

PMID- 30207963
TI  - Bayesian Data Fusion of Gene Expression and Histone Modification Profiles for
      Inference of Gene Regulatory Network.
AB  - Accurately reconstructing gene regulatory networks (GRNs) from high-throughput
      gene expression data has been a major challenge in systems biology for decades.
      Many approaches have been proposed to solve this problem. However, there is still
      much room for the improvement of GRN inference. Integrating data from different
      sources is a promising strategy. Epigenetic modifications have a close
      relationship with gene regulation. Hence, epigenetic data such as histone
      modification profiles can provide useful information for uncovering regulatory
      interactions between genes. In this paper, we propose a method to integrate
      epigenetic data into the inference of GRNs. In particular, a dynamic Bayesian
      network (DBN) is employed to infer gene regulations from time-series gene
      expression data. Epigenetic data (histone modification profiles here) are
      integrated into the prior probability distribution of the Bayesian model. Our
      method has been validated on both synthetic and real datasets. Experimental
      results show that the integration of epigenetic data can significantly improve
      the performance of GRN inference. As more epigenetic datasets become available,
      our method would be useful for elucidating the gene regulatory mechanisms driving
      various cellular activities. The source code and testing datasets are available
      at https://github.com/Zheng-Lab/MetaGRN/tree/master/histonePrior.

PMID- 30207964
TI  - Digital Multiplierless Realization of Coupled Wilson Neuron Model.
AB  - The human brain is composed of 1011 neurons with a switching speed of about 1 ms.
      Studying spiking neural networks, including modeling, simulation and
      implementation of biological neuron models help to learn about the brain and
      related diseases or to design more efficient bio-mimic processors and smarter
      robots. Such applications have made this part of neuromorphic researches very
      popular. In this paper, Wilson neuron model has been implemented as an
      approximation of Hodgkin-Huxley biological model that is adjusted for efficient
      digital realization on the platforms. Results show that the proposed model can
      adequately reproduce neuron dynamical behaviors. Hardware implementation on FPGA
      shows that our modifications on Wilson original model imitate the biological
      behavior of neurons, besides using feasibility, targeting a low-cost and high
      efficiency. The modifications raised a 15% speed-up compared with the original
      model. The mean NRMSE, RMSE and the MAE parameters are 6.43, 0.44 and 0.31,
      respectively.

PMID- 30207965
TI  - Universal Approximation Capability of Broad Learning System and Its Structural
      Variations.
AB  - After a very fast and efficient discriminative broad learning system (BLS) that
      takes advantage of flatted structure and incremental learning has been developed,
      here, a mathematical proof of the universal approximation property of BLS is
      provided. In addition, the framework of several BLS variants with their
      mathematical modeling is given. The variations include cascade, recurrent, and
      broad-deep combination structures. From the experimental results, the BLS and its
      variations outperform several exist learning algorithms on regression performance
      over function approximation, time series prediction, and face recognition
      databases. In addition, experiments on the extremely challenging data set, such
      as MS-Celeb-1M, are given. Compared with other convolutional networks, the
      effectiveness and efficiency of the variants of BLS are demonstrated.

PMID- 30207966
TI  - Multimodal Medical Image Fusion Based on Fuzzy Discrimination with Structural
      Patch Decomposition.
AB  - Multimodal medical image fusion, emerging as a hot topic, aims to fuse images
      with complementary multi-source information. In this paper, we propose a novel
      multimodal medical image fusion method based on structural patch decomposition
      (SPD) and fuzzy logic technology. First, the SPD method is employed to extract
      two salient features for fusion discrimination. Next, two novel fusion decision
      maps called an incomplete fusion map and supplemental fusion map are constructed
      from salient features. In this step, the supplemental map is constructed by our
      defined two different fuzzy logic systems. The supplemental and incomplete maps
      are then combined to construct an initial fusion map. The final fusion map is
      obtained by processing the initial fusion map with a Gaussian filter. Finally, a
      weighted average approach is adopted to create the final fused image.
      Additionally, an effective color medical image fusion scheme that can effectively
      prevent color distortion and obtain superior diagnostic effects is also proposed
      to enhance fused images. Experimental results clearly demonstrate that the
      proposed method outperforms state-of-the-art methods in terms of subjective
      visual and quantitative evaluations.

PMID- 30207967
TI  - Glycemic Control of People with Type 1 Diabetes based on Probabilistic
      Constraints.
AB  - The objective of the paper is to develop an open loop insulin infusion profile
      which is capable of controlling the blood glucose level of people with Type 1
      diabetes in the presence of broad uncertainties such as inter-patient variability
      and unknown meal quantity. For illustrative purposes, the Bergman model in
      conjunction with a gut-dynamics model is chosen to represent the human glucose
      insulin dynamics. A recently developed sampling based uncertainty quantification
      approach is used to determine the statistics (mean and variance) of the evolving
      states in the model. These statistics are utilized to define chance constraints
      in an optimization framework. The solution obtained shows that under the
      assumptions made on the distribution of the model parameters, all possible
      glucose trajectories over time satisfy the desired glycemic control goals. The
      solution is also validated on the FDA approved Type 1 Diabetes Metabolic
      Simulator (T1DMS) suggesting that the proposed algorithm is highly suitable for
      human subjects.

PMID- 30207968
TI  - OpenCLIPER: an OpenCL-based C++ Framework for Overhead-Reduced Medical Image
      Processing and Reconstruction on Heterogeneous Devices.
AB  - Medical image processing is often limited by the computational cost of the
      involved algorithms. Whereas dedicated computing devices (GPUs in particular)
      exist and do provide significant efficiency boosts, they have an extra cost of
      use in terms of housekeeping tasks (device selection and initialization, data
      streaming, synchronization with the CPU and others), which may hinder developers
      from using them. This paper describes an OpenCL-based framework that is capable
      of handling dedicated computing devices seamlessly and that allows the developer
      to concentrate on image processing tasks. The framework handles automatically
      device discovery and initialization, data transfers to and from the device and
      the file system and kernel loading and compiling. Data structures need to be
      defined only once independently of the computing device; code is unique,
      consequently, for every device, including the host CPU. Pinned memory/buffer
      mapping is used to achieve maximum performance in data transfers. Code fragments
      included in the paper show how the computing device is almost immediately and
      effortlessly available to the users algorithms, so they can focus on productive
      work. Code required for device selection and initialization, data loading and
      streaming and kernel compilation is minimal and systematic. Algorithms can be
      thought of as mathematical operators (called processes), with input, output and
      parameters, and they may be chained one after another easily and efficiently.
      Also for efficiency, processes can have their initialization work split from
      their core workload, so process chains and loops do not incur in performance
      penalties. Algorithm code is independent of the device type targeted.

PMID- 30207969
TI  - Weakly-Supervised Learning of Metric Aggregations for Deformable Image
      Registration.
AB  - Deformable registration has been one of the pillars of biomedical image
      computing. Conventional approaches refer to the definition of a similarity
      criterion that, once endowed with a deformation model and a smoothness
      constraint, determines the optimal transformation to align two given images. The
      definition of this metric function is among the most critical aspects of the
      registration process. We argue that incorporating semantic information (in the
      form of anatomical segmentation maps) into the registration process will further
      improve the accuracy of the results. In this paper, we propose a novel weakly
      supervised approach to learn domain specific aggregations of conventional metrics
      using anatomical segmentations. This combination is learned using latent
      structured support vector machines (LSSVM). The learned matching criterion is
      integrated within a metric free optimization framework based on graphical models,
      resulting in a multi-metric algorithm endowed with a spatially varying similarity
      metric function conditioned on the anatomical structures. We provide extensive
      evaluation on three different datasets of CT and MRI images, showing that learned
      multi-metric registration outperforms single-metric approaches based on
      conventional similarity measures.

PMID- 30207970
TI  - Finite-Horizon Optimal Consensus Control for Unknown Multiagent State-Delay
      Systems.
AB  - This paper investigates finite-horizon optimal consensus control problem for
      unknown multiagent systems with state delays. It is well known that optimal
      consensus control is the solutions to the coupled Hamilton-Jacobi-Bellman (HJB)
      equations. An off-policy reinforcement learning (RL) algorithm is developed to
      learn the two-stage optimal consensus solutions to the coupled time-varying HJB
      equations using the measurable state data instead of the knowledge of the state
      delayed system dynamics. Subsequently, for each agent, a single critic neural
      network (NN) is utilized to approximate the time-varying cost function and help
      to calculate optimal consensus control policy. Based on the method of weighted
      residuals, adaptive weight update laws for the critic NNs are proposed. Finally,
      the simulation results are provided to illustrate the effectiveness of the
      proposed off-policy RL method.

PMID- 30207971
TI  - Edge Convergence Problems on Signed Networks.
AB  - This paper focuses on characterizing edge dynamics of signed networks subject to
      both cooperative and antagonistic interactions and copes with the state
      convergence problems of the resulting edge systems. To represent the two
      competitive classes of interactions that emerge in signed networks, signed
      digraphs are adopted and the relevant edge Laplacian matrices are introduced,
      with which an edge-based distributed protocol is presented. The relation between
      the edge Laplacian matrix and the structural balance (or unbalance) of a signed
      digraph is disclosed by taking advantage of properties of undirected cycles.
      Further, it is shown that for a signed network, the state of its edge system
      converges to a constant vector, regardless of whether its associated signed
      digraph is structurally balanced or unbalanced. This result does not need to
      impose the assumption upon the digon sign-symmetry of the signed digraph that is
      generally required by the node-based distributed protocols. In particular, the
      state convergence results of edges can be exploited to handle traditional
      bipartite consensus problems for the nodes of signed networks. Simulation
      examples are given to illustrate the effectiveness of the edge-based analysis
      method proposed for signed networks.

PMID- 30207972
TI  - Output Containment Control for Heterogeneous Linear Multiagent Systems With Fixed
      and Switching Topologies.
AB  - In this paper, we investigate the output containment control problem for a
      network of heterogeneous linear multiagent systems. The control target is to
      drive the outputs of the followers into the convex hull spanned by the leaders.
      To this end, we first derive a necessary condition imposed on both system
      dynamics and network topology from the viewpoint of internal model principle.
      Then, based on the necessary condition, we utilize a dynamic controller to drive
      the outputs of the leaders and followers to track the reference trajectories to
      achieve containment exponentially. We consider a general network topology which
      only contains a united spanning tree. Both fixed and dynamic network topologies
      are taken into consideration. Then, the optimal control problem for containment
      is further studied. An optimal control law is constructed from an algebraic
      Riccati equation, which is proved to be a stabilizing one as well. Finally, a
      reinforcement learning algorithm is introduced to solve the optimal control
      problem on line without the knowledge the system dynamics. Simulations are given
      at last to validate our theoretical findings.

PMID- 30207973
TI  - Evolutionary Many-Objective Algorithm Using Decomposition-Based Dominance
      Relationship.
AB  - Decomposition-based evolutionary algorithms have shown great potential in many
      objective optimization. However, the lack of theoretical studies on decomposition
      methods has hindered their further development and application. In this paper, we
      first theoretically prove that weight sum, Tchebycheff, and penalty boundary
      intersection decomposition methods are essentially interconnected. Inspired by
      this, we further show that highly customized dominance relationship can be
      derived from decomposition for any given decomposition vector. A new evolutionary
      algorithm is then proposed by applying the customized dominance relationship with
      adaptive strategy to each subpopulation of multiobjective to multiobjective
      framework. Experiments are conducted to compare the proposed algorithm with five
      state-of-the-art decomposition-based evolutionary algorithms on a set of well
      known scaled many-objective test problems with 5 to 15 objectives. Simulation
      results have shown that the proposed algorithm can make better use of the
      decomposition vectors to achieve better performance. Further investigations on
      unscaled many-objective test problems verify the robust and generality of the
      proposed algorithm.

PMID- 30207974
TI  - Adaptive Event-Triggered Transmission Scheme and Hinfinity Filtering Co-Design
      Over a Filtering Network With Switching Topology.
AB  - This paper addresses the distributed adaptive event-triggered Hinfinity filtering
      problem for a class of sector-bounded nonlinear system over a filtering network
      with time-varying and switching topology. Both topology switching and adaptive
      event-triggered mechanisms (AETMs) between filters are simultaneously considered
      in the filtering network design. The communication topology evolves over time,
      which is assumed to be subject to a nonhomogeneous Markov chain. In consideration
      of the limited network bandwidth, AETMs have been used in the information
      transmission from the sensor to the filter as well as the information exchange
      among filters. The proposed AETM is characterized by introducing the dynamic
      threshold parameter, which provides benefits in data scheduling. Moreover, the
      gain of the correction term in the adaptive rule varies directly with the
      estimation error and inversely with the transmission error. The switching
      filtering network is modeled by a Markov jump nonlinear system. The stochastic
      Markov stability theory and linear matrix inequality techniques are exploited to
      establish the existence of the filtering network and further derive the filter
      parameters. A co-design algorithm for determining Hinfinity filters and the event
      parameters is developed. Finally, some simulation results on a continuous stirred
      tank reactor and a numerical example are presented to show the applicability of
      the obtained results.

PMID- 30207975
TI  - Delay-Distribution-Dependent Hinfinity State Estimation for Discrete-Time
      Memristive Neural Networks With Mixed Time-Delays and Fading Measurements.
AB  - This paper addresses the Hinfinity state estimation issue for a sort of
      memristive neural networks in the discrete-time setting under randomly occurring
      mixed time-delays and fading measurements. The main purpose of the addressed
      issue is to propose a state estimator design algorithm that ensures the error
      dynamics of the state estimation to be stochastically stable with a prespecified
      Hinfinity disturbance attenuation index. We put forward certain switching
      functions to account for the discrete-time yet state-dependent characteristics of
      the memristive connection weights. By resorting to the robust analysis theory and
      the Lyapunov-functional analysis theory, we derive some sufficient conditions to
      guarantee the desired estimation performance. The derived sufficient conditions
      rely not only on the size of discrete time-delays and the probability
      distribution law of the distributed time-delays but also on the statistics
      information of the coefficients of the adopted Rice fading model. Based on the
      established existence conditions, the gain matrices of the desired estimator are
      obtained by means of the feasibility of a set of matrix inequalities that can be
      checked efficiently via available software packages. Finally, the numerical
      simulation results are provided to show the validity of the main results.

PMID- 30207976
TI  - Recurrent Broad Learning Systems for Time Series Prediction.
AB  - The broad learning system (BLS) is an emerging approach for effective and
      efficient modeling of complex systems. The inputs are transferred and placed in
      the feature nodes, and then sent into the enhancement nodes for nonlinear
      transformation. The structure of a BLS can be extended in a wide sense.
      Incremental learning algorithms are designed for fast learning in broad
      expansion. Based on the typical BLSs, a novel recurrent BLS (RBLS) is proposed in
      this paper. The nodes in the enhancement units of the BLS are recurrently
      connected, for the purpose of capturing the dynamic characteristics of a time
      series. A sparse autoencoder is used to extract the features from the input
      instead of the randomly initialized weights. In this way, the RBLS retains the
      merit of fast computing and fits for processing sequential data. Motivated by the
      idea of ''fine-tuning'' in deep learning, the weights in the RBLS can be updated
      by conjugate gradient methods if the prediction errors are large. We exhibit the
      merits of our proposed model on several chaotic time series. Experimental results
      substantiate the effectiveness of the RBLS. For chaotic benchmark datasets, the
      RBLS achieves very small errors, and for the real-world dataset, the performance
      is satisfactory.

PMID- 30207977
TI  - Observer-Based Consensus Control for Discrete-Time Multiagent Systems With Coding
      Decoding Communication Protocol.
AB  - In this paper, the consensus control problem is investigated for a class of
      discrete-time networked multiagent systems (MASs) with the coding-decoding
      communication protocol (CDCP). Under a directed communication topology, an
      observer-based control scheme is proposed for each agent by utilizing the
      relative measurement outputs between the agent itself and its neighboring ones.
      The signal delivery is in a digital manner, which means that only the sequence of
      finite coded signals is sent from the observer to the controller. To be specific,
      the observed data is encoded to certain codewords by a designed coder via the
      CDCP, and the received codewords are then decoded by the corresponding decoder at
      the controller side. The purpose of the addressed problem is to design an
      observer-based controller such that the close-loop MAS achieves the expected
      consensus performance. First, with the help of the input-to-state stability
      theory, a theoretical framework for the detectability is established for
      analyzing and designing the CDCP. Then, under such a communication protocol, some
      sufficient conditions for the existence of the proposed observer-based controller
      are derived to guarantee the asymptotic consensus of the MASs. In addition, the
      controller parameter is explicitly determined in terms of the solution to certain
      matrix inequalities associated with the information of the communication
      topology. Finally, a simulation example is given to demonstrate the effectiveness
      of the developed control strategy.

PMID- 30207978
TI  - Automatic Leader-Follower Persistent Formation Generation With Minimum Agent
      Movement in Various Switching Topologies.
AB  - This paper presents the generation strategy, motion planning, and switching
      topologies of a distance-based leader-follower relation-invariable persistent
      formation (RIPF) of multiagent systems (MASs). An efficient algorithm is designed
      to find out if a persistent formation can be generated from a rigid graph.
      Derived from the properties of a rigid graph, the algorithm to generate RIPF from
      any initial location is presented. In order to generate different RIPFs in the
      switching topology, state and transition matrices are introduced. To achieve the
      minimum agent-movement among RIPFs, a downward-tree combinatorial optimization
      algorithm is presented. In the end, with the selected minimum agent-movement
      RIPF, a control law is designed to drive initial RIPF to desired RIPF with given
      distances among agents. Simulation results show the proposed generation method,
      control law, and downward-tree are effective to realize the desired formation.

PMID- 30207979
TI  - Can naloxone prescription and overdose training for opioid users work in family
      practice? Perspectives of family physicians.
AB  - OBJECTIVE: To explore family physicians' attitudes toward prescribing naloxone to
      at-risk opioid users, as well as to determine the opportunities and challenges
      for expanding naloxone access to patients in family practice settings. DESIGN:
      One-hour focus group session and SWOT (strengths, weaknesses, opportunities, and
      threats) analysis. SETTING: Workshop held at the 2012 Family Medicine Forum in
      Toronto, Ont. PARTICIPANTS: Seventeen conference attendees from 3 Canadian cities
      who practised in various family practice settings and who agreed to participate
      in the workshop. METHODS: The workshop included an overview of information about
      naloxone distribution and overdose education programs, followed by group
      discussion in smaller focus groups. Participants were instructed to focus their
      discussion on the question, "Could this [overdose education and naloxone
      prescription] work in your practice?" and to record notes using a standardized
      discussion guide based on a SWOT analysis. Two investigators reviewed the forms,
      extracting themes using an open coding process. MAIN FINDINGS: Some participants
      believed that naloxone could be used safely among family practice patients, that
      the intervention fit well with their clinical practice settings, and that its use
      in family practice could enhance engagement with at-risk individuals and create
      an opportunity to educate patients, providers, and the public about overdose.
      Participants also indicated that the current guidelines and support systems for
      prescribing or administering naloxone were inadequate, that medicolegal
      uncertainties existed for those who prescribed or administered naloxone, and that
      high-quality evidence about the intervention's effectiveness in family practice
      was lacking. CONCLUSION: Family physicians believe that overdose education and
      naloxone prescription might provide patients at risk of opioid overdose in their
      practices with broad access to a potentially lifesaving intervention. However,
      they explain that there are key barriers currently limiting widespread
      implementation of naloxone use in family practice settings.

PMID- 30207980
TI  - Reply to comment on 'origins of the changing detector response in small
      megavoltage photon radiation fields'.
AB  - Andreo and Benmakhlouf (2017 Phys. Med. Biol. 62 1518-32) have disputed a finding
      of Scott et al (2012 Phys. Med. Biol. 57 4461-76) that the variation with field
      size of the response of small ion chambers and solid-state dosimeters in small
      megavoltage photon radiation fields can largely be attributed to density. Further
      evidence for this finding was provided by Fenwick et al (2018 Phys. Med. Biol. 63
      125003), but Andreo and Benmakhlouf (2018 Phys. Med. Biol. 63 125003) have now
      challenged the methodology used in that study. Specifically, Andreo and
      Benmakhlouf suggest that mass stopping-powers of fictitious materials used in
      Monte Carlo radiation transport calculations should be adjusted with material
      density according to the polarization effect, as if the materials were real and
      created by compressing other real materials. In this reply, we observe that
      fictitious materials are not real, and therefore their densities, mass stopping
      powers and microscopic radiation interaction cross-sections can be freely and
      independently chosen to provide the clearest answers to the questions being
      studied. And we note that the key role played by density in small field detector
      response was further confirmed by our group back in 2013, using fictitious
      materials in which mass stopping-powers were adjusted with density, as preferred
      by Andreo and Benmakhlouf, as well as being held fixed, with very similar results
      being obtained in both circumstances (Underwood et al 2013a Med. Phys. 40
      082102).

PMID- 30207981
TI  - Machine learning for intraoperative prediction of viability in ischemic small
      intestine.
AB  - OBJECTIVE: Evaluation of intestinal viability is essential in surgical decision
      making in patients with acute intestinal ischemia. There has been no substantial
      change in the mortality rate (30%-93%) of patients with acute mesenteric ischemia
      (AMI) since the 1980s. As the accuracy from the first laparotomy alone is 50%,
      the gold standard is a second-look laparotomy, increasing the accuracy to 87%
      89%. This study investigates the use of machine learning to classify intestinal
      viability and histological grading in pig jejunum, based on multivariate time
      series of bioimpedance sensor data. APPROACH: We have previously used a
      bioimpedance sensor system to acquire electrical parameters from perfused,
      ischemic and reperfused pig jejunum (7  +  15 pigs) over 1-16 h of ischemia and 1
      8 h of reperfusion following selected durations of ischemia. In this study we
      compare the accuracy of using end-point bioimpedance measurements with a
      feedforward neural network (FNN), versus the accuracy when using a recurrent
      neural network with long short-term memory units (LSTM-RNN) with bioimpedance
      data history over different periods of time. MAIN RESULTS: Accuracies in the
      range of what has been reported clinically can be achieved using FNN's on a
      single bioimpedance measurement, and higher accuracies can be achieved when
      employing LSTM-RNN on a sequence of data history. SIGNIFICANCE: Intraoperative
      bioimpedance measurements on intestine of suspect viability combined with machine
      learning can increase the accuracy of intraoperative assessment of intestinal
      viability. Increased accuracy in intraoperative assessment of intestinal
      viability has the potential to reduce the high mortality and morbidity rate of
      the patients.

PMID- 30207982
TI  - Comment on 'Collimated proton pencil-beam scanning for superficial targets:
      impact of the order of range shifter and aperture'.
AB  - We read with interest the study by Baumer et al (2018 Phys. Med. Biol. 63
      085020), in particular that their conclusions are in contrast to those of our
      earlier paper (Winterhalter et al 2018 Phys. Med. Biol. 63 025022), namely that
      positioning the collimating aperture downstream of the range shifter leads to a
      superior penumbra. In contrast, we found sharper penumbras for the PSI scanning
      Gantry when the aperture is positioned upstream of the range shifter. We have run
      additional Monte Carlo simulations with components derived from the paper of
      Baumer et al (2018 Phys. Med. Biol. 63 085020), but without modifying the beam
      description. As such, we obtain a relative penumbra reduction of 13% if the
      aperture is positioned downstream of the ranges shifter, which lies well within
      the measured/calculated penumbra reductions of Baumer et al (2018 Phys. Med.
      Biol. 63 085020) of 17%/11%. The conclusions of Baumer et al (2018 Phys. Med.
      Biol. 63 085020) and our previous work are therefore complementary, given the
      differences in the thicknesses of the beam modifying devices used in the two
      works. In addition, our analysis implies that initial beam characteristics are
      less important in determining the best order of components.

PMID- 30207983
TI  - Threshold-based fall detection using a hybrid of tri-axial accelerometer and
      gyroscope.
AB  - OBJECTIVE: Falling is an important health maintenance issue for the elderly and
      people with movement disorders, strokes and multiple sclerosis. With the
      development of light, low-cost wearable technology, inertia-based fall detection
      has gained much attention. However, some large movements, such as jumping and
      postural changes, are frequently confounded with falls. For example, commonly
      used fall detection methods based on acceleration amplitude produce a large
      number of false alerts unless they are combined with post-fall posture
      identification. In this paper, we propose two new inertial parameters to improve
      the selectivity of threshold-based fall detection methods, and evaluate
      strategies to distinguish falls from other activities of daily life (ADLs).
      APPROACH: We define two new inertial parameters, acceleration cubic-product-root
      magnitude (ACM) and angular velocity cubic-product-root magnitude (AVCM). Along
      with acceleration magnitude (AM), we test threshold-based fall detection methods
      based on single parameters and combinations. We collected inertial data on four
      types of simulated falls and eight types of ADLs from a study with 15
      participants wearing a chest-mounted sensor with accelerometer and gyroscope. Two
      public datasets, UMAFall and Cognent Labs, were also included to evaluate fall
      detection methods. MAIN RESULTS: We chose the detection threshold with 99%
      sensitivity and the best possible specificity. The hybrid of AM, ACM and AVCM
      method had a lower rate of misclassification than single-parameter methods. Leave
      one-out cross-validation shows that the hybrid fall detection method can achieve
      both high specificity and high sensitivity. SIGNIFICANCE: Using multiple inertial
      parameters improves the specificity of fall detection.

PMID- 30207984
TI  - Comment on 'Origins of the changing detector response in small megavoltage photon
      radiation fields'.
AB  - A clarification is made with regard to the erroneous statement that assigns an
      incorrect conclusion to a paper by Andreo and Benmakhlouf (2017 Phys. Med. Biol.
      62 1518-32) and in relation to other comments on that work. It is also argued
      that the Monte Carlo calculations made by the authors are based on physically
      incorrect input data for the fictitious materials used in their simulations, as
      density-effect corrections and stopping powers must correspond to the specific
      properties assigned to the fictitious material. Hence, their conclusions remain
      to be demonstrated using reliable input datasets.

PMID- 30207985
TI  - Intercomparison of methods for measurement of dielectric properties of biological
      tissues with a coaxial sensor at millimeter-wave frequencies.
AB  - Coaxial sensors are effective for measurement of dielectric properties of
      biological tissues. Several measurement methods used to derive dielectric
      properties have been investigated for the measurement with a coaxial sensor at
      microwave frequencies. While the measurement accuracy depends on the method used,
      there has been insufficient intercomparison of these methods and their model
      approximation errors. On the other hand, we have developed a coaxial sensor for
      the measurement of complex permittivity at millimeter-wave (MMW) frequencies of
      up to 100 GHz. However, the scarcity of reference data at MMW frequencies makes
      the validation of the measurement system difficult. Thus, it is essential to
      clarify the model approximation error of the method used in the measurement
      system, particularly at MMW frequencies. This study aims to clarify the model
      approximation errors of methods for dielectric property measurement using a
      coaxial sensor at MMW frequencies. The model approximation errors were assessed
      by comparing results obtained by the methods with those based on the theoretical
      formula of the full-wave modal expression of Maxwell's equations. The measurement
      uncertainty for the theoretical formula was estimated for a standard liquid
      sample to clarify the contribution of the model approximation errors to the
      uncertainty. Furthermore, the methods were applied to the measurement of porcine
      tissues at body temperature, and the measurement accuracy and usability for
      measurement at MMW frequencies are discussed.

PMID- 30207986
TI  - Comparison between probabilistic and Wiener-Granger causality in assessing
      modifications of the cardiac baroreflex control with age.
AB  - BACKGROUND: Probabilistic causality (PC) is a framework for checking that the
      occurrence of a cause raises the probability of the effect by comparing the
      probability of the effect conditioned and unconditioned to the cause. Even though
      it is less frequently utilized with respect to the more traditional model-based
      Wiener-Granger causality (WGC) that is based on the predictability improvement of
      an effect resulting from the inclusion of the presumed cause in the multivariate
      linear regression model, PC has the advantage of being model-free. OBJECTIVE: The
      aim of the study is to apply the PC framework to assess the evolution of cardiac
      baroreflex control with age from spontaneous fluctuations of heart period (HP)
      and systolic arterial pressure (SAP) and to compare it to the more common WGC
      approach. APPROACH: We studied 100 healthy humans (54 males, age: 21-70 years, 20
      subjects for each 10 years bin). HP and SAP were extracted on a beat-to-beat
      basis from 5 min recordings of electrocardiogram and plethysmographic arterial
      pressure at rest in supine position (REST) and during active standing (STAND)
      under spontaneous breathing. The WGC ratio (WGCR) was computed as the log ratio
      of the prediction error variance of the autoregressive model on HP to that on HP
      with exogenous SAP. The PC ratio (PCR) was computed as the probability of
      observing an HP ramp given an associated parallel SAP variation divided by the
      probability of observing an HP ramp. MAIN RESULTS: The WGCR and PCR suggested the
      gradual impairment of cardiac baroreflex with age, especially during STAND.
      Moreover, they were significantly associated both at REST and during STAND but
      the degree of the PCR-WGCR association was weak. SIGNIFICANCE: PC can be
      effectively exploited to assess modification of the cardiovascular control during
      senescence even though a limited agreement was observed with WGC.

PMID- 30207987
TI  - Monte Carlo determination of k Q and k Qmsr values for the exradin A26 ionisation
      chamber for the Varian TrueBeam.
AB  - We have calculated conversion factors, k Q for the A26 micro ionisation chamber
      along with machine specific reference beam quality factors, k Qmsr, for a number
      of field sizes and beam qualities for the Varian TrueBeam accelerator. The A12
      ionisation chamber was simulated alongside the A26, so as to validate against
      known literature values. Both ionisation chambers were modelled from manufacturer
      data sheets and schematics. The egs_chamber Monte Carlo user code was used to
      simulate each absorbed dose relevant to the beam quality conversion factors k Q
      and k Qmsr. Tabulated spectra for beam energies of 4 through 25 MV were used in
      the k Q calculations for both investigated chambers. Varian TrueBeam phase space
      files for 6 MV flattened as well as 6 and 10 MV unflattened beams were used in
      the simulations of the A26 chamber in field sizes from 2  *  2 cm square to 20  *
      20 cm square in order to determine k Qmsr values. The PDD(10)x  values of the
      tabulated spectra were found to be within variation between studies, with an
      average deviance of 0.4% from one prior study. The simulated A12 k Q values
      matched the accepted literature values with an average variation of  <0.1%. The
      A26 k Q values match the manufacturer provided values to within 0.5%. For all
      investigated field sizes the k Qmsr values are within 0.006 of unity. There is no
      published data for this chamber for a direct comparison, but there is similarity
      between these results and results from other chambers regularly used in similar
      circumstances. Furthermore, the agreement of the simulated k Q values to knowns,
      and the agreement of the PDD(10)x  factors would suggest the correctness and
      accuracy of the study.

PMID- 30207988
TI  - Forward osmosis treatment of effluents from dairy and automobile industry -
      results from short-term experiments to show general applicability.
AB  - Forward osmosis (FO) is a potential membrane technology to treat wastewater
      energy efficiently with low fouling. In laboratory-scale experiments, six
      effluents from a dairy and an automobile production plant were tested to find out
      if FO is an applicable treatment technology. Permeate flux and reverse salt flux
      were determined in nine test series with three subsequent 5 h experiments each.
      In between, the membrane was cleaned with deionized water. Membrane performance
      tests before each experiment were used to monitor membrane performance and
      fouling. Samples were analysed and the T/M-value was introduced to indicate which
      substances caused fouling. Dairy cheese brine was a suitable DS. Here, permeate
      fluxes were 21.0 and 15.1 L/(m2.h). Automobile cooling tower water and wastewater
      from cathodic dip painting were also used as DS. However, permeate fluxes were
      below 1.1 L/(m2.h). The tested FS, reverse osmosis concentrate from dairy
      wastewater treatment, rinsing water and wastewater from automobile cathodic dip
      painting, as well as wastewater from automobile paint shop pre-treatment, showed
      good performance regarding the permeate flux of between 7.9 and 19.4 L/(m2.h).
      Membrane performance test showed that some of the effluents lead to permeate flux
      reduction due to fouling. Different cleaning-in-place methods were examined.
      Eventually, permeate flux was restored.

PMID- 30207989
TI  - Enhanced biosorption of Cr(VI) using cotton fibers coated with chitosan - role of
      ester bonds.
AB  - We report on the role of ester bonds in the enhanced removal of hexavalent
      chromium from water using cotton fibers coated with chitosan. Adsorption
      capacities up to five times higher than those of the unmodified fibers were
      observed when the cotton fibers were exposed to an NaOH, followed by citric acid
      (0.97 M), and a chitosan solution (2%). We found that the use of NaOH favors the
      formation of ester bonds over amide bonds on the surface of the cotton fibers.
      This increase in the surface density of ester bonds generates an increase in the
      amount of exposed amino groups from the chitosan, hence increasing the removal
      capacity of the modified fibers. Experimental results also reveal that the
      adsorption is induced by the electrostatic attraction between the protonated
      amino groups on the surface and the negatively charged chromium ions in the
      water. Adsorption isotherms and kinetic studies indicated that the adsorption
      process fits the Langmuir and the Freundlich isotherm models as well as the
      pseudo-first and pseudo-second order kinetic models. These results can open a new
      avenue for the manufacturing of fibers with enhanced removal capacities for
      hexavalent chromium.

PMID- 30207990
TI  - Fabrication of Zr-doped TiO2/chitosan composite catalysts with enhanced visible
      light-mediated photoactivity for the degradation of Orange II dye.
AB  - Zirconium/titanium/chitosan (Zr/Ti/CHT) composite catalysts were synthesized by
      sol-gel method using different chitosan amounts (5-20 wt.%) and their activity in
      the photocatalytic degradation of Orange II dye was evaluated for the first time.
      The results were compared with Zr/Ti, Zr/CHT and Ti/CHT catalysts. The composite
      catalysts were characterized by X-ray diffraction (XRD), Fourier transform
      infrared spectroscopy, scanning electron microscopy and X-ray photoelectron
      spectroscopy analysis. XRD analysis revealed that the Zr/Ti/CHT composite
      catalyst showed high crystallinity of anatase TiO2 phase. Photocatalytic
      experiments showed that adding CHT into the catalyst structure increased the
      photocatalytic degradation under visible light irradiation. Also, the first-order
      reaction rate constant, kapp, was calculated using the Langmuir-Hinshelwood (L-H)
      equation. The kapp values were found to be 0.009, 0.0013, 0.012 and 0.014 min-1
      for Zr/Ti, Zr/CHT, Ti/CHT and Zr/Ti/CHT, respectively. According to stability
      tests, after the first cycle Orange II dye degradation was found to be 95%, while
      it was 37% after the fifth cycle. The results showed that the composite catalyst
      could be used several times for Orange II dye degradation.

PMID- 30207991
TI  - Effect of inorganic salt ions on the adsorption of quinoline using coal powder.
AB  - In this study, coal powder was used as the adsorbent for quinoline. The effect of
      inorganic salt ions on the adsorption was explored, and the results suggest that
      the addition of inorganic salt ions can enhance both the removal rate and the
      amount of quinoline adsorbed. The removal rate and adsorbed amount of quinoline
      were 83.87% and 1.26 mg/g without inorganic salt ions. Under the same adsorption
      conditions, the removal rate and adsorbed amount of quinoline could reach 90.21%
      and 1.35 mg/g when Na+ was present in the solution, and 94.47% and 1.42 mg/g with
      the presence of Ca2+. In addition, the adsorption of quinoline using coal fitted
      the Freundlich isothermal adsorption model. Changes in the Gibbs free energy,
      entropy and heat of adsorption were all negative, indicating that the adsorption
      was spontaneous and exothermic. The changes in the absolute value of Gibbs free
      energy under both Na+ and Ca2+ were higher than that in the blank(without
      inorganic salt ions). The pseudo-second-order kinetic model was found to fit the
      adsorption kinetic data well, and the activation energy of adsorption under Na+
      and Ca2+ were lower than that in the blank. These indicate that the addition of
      inorganic salt ions was beneficial to the adsorption process.

PMID- 30207992
TI  - Improved adsorption of Congo red by nanostructured flower-like Fe(II)-Fe(III)
      hydroxy complex.
AB  - Amorphous Fe(II)-Fe(III) hydroxy complex with flower-like nanostructure was
      synthesized by ferric reduction using a microwave-assisted ethylene glycol
      approach. Here we investigated the correlation between its chemical composition
      and the removal rate for Congo red (CR) dye. The results showed that the
      amorphous complex had similar reduction and anion exchange capacities to the
      green rust. Due to the synergistic effect of attractive electrostatic
      interaction, anion exchange, ferrous redox and hydrogen bonding, the Fe(II)
      Fe(III) hydroxy complex exhibited strong adsorption of CR with an estimated
      adsorption capacity up to 513 mg g-1. In contrast, the Fe(III) hydroxy complex
      had an adsorption capacity of 296 mg g-1 because of the predominant mechanism
      based on the electrostatic interaction. The present study provides a facile
      synthesis of nanostructured iron hydroxy complex, with superior performance in
      adsorbing CR.

PMID- 30207993
TI  - Performance and microbial community of the completely autotrophic nitrogen
      removal over nitrite process with a submerged aerated biological filter.
AB  - Stable performance is a technical problem in the completely autotrophic nitrogen
      removal over nitrite (CANON) process with one single stage, which needs to be
      addressed. In the current work, a laboratory-scale submerged aerated biological
      filter (SABF) with a 3-L working volume was introduced into the CANON process to
      enhance its stable performance for 290 days under the following conditions:
      temperature of 30 +/- 1  degrees C and dissolved oxygen (DO) level of 0.2-0.8
      mg.L-1. The results showed that the average ammonium nitrogen removal
      efficiencies (ANRE) and total nitrogen removal efficiencies (TNRE) were 97.4% and
      75.7%, respectively. A 16S rRNA gene high-throughput sequencing technology
      confirmed the phyla Proteobacteria and Planctomycetes as the ammonium oxidizing
      bacteria (AOB) and anaerobic ammonia-oxidizing bacteria (AnAOB) of this CANON
      process with SABF, respectively. The major contributor to nitrogen removal was
      the genus Candidatus Brocadia, in Brocadiae. The aim is to present an effective
      strategy as a reference for the design of full-scale plant for the CANON process.

PMID- 30207994
TI  - Start-up performance of anaerobic/aerobic/anoxic-sequencing batch reactor (SBR)
      augmented with denitrifying polyphosphate-accumulating organism (DPAO) and their
      gene analysis.
AB  - This paper was aimed at investigating the bio-augmentation performance of
      anaerobic/aerobic/anoxic-type sequencing batch reactor (SBR) during its start-up
      period by introducing a strain of denitrifying polyphosphate-accumulating
      organism (DPAO). Two SBR reactors were inoculated to study the start-up
      performance, with one for DPAO introduction and the other as the control
      specimen. A comparison, of microbial community diversity based on the reactor
      which obtained a better performance, was made between polymerase chain reaction
      denaturing gradient gel electrophoresis (PCR-DGGE) analyses encoded by 16S rRNA
      and functional genes (nirS, nirK). The results indicated that the introduction of
      DPAO had a positive effect on the biological system, including a reduction of the
      start-up period, the improvement of sludge characteristics and the removal
      efficiency of nutrients, especially for phosphorus. By comparing the phylogenetic
      relationship of 16S rRNA and functional genes (nirS, nirK) of the reactor
      augmented with DPAO, it could be found that the phylogenetic relationship of
      these genes were remarkably inconsistent with each other. Therefore, 16SrRNA
      should not be used to determine the microbial community diversity of functional
      bacteria which could accomplish denitrification, and gene nirK should not be
      neglected when determining functional bacteria.

PMID- 30207995
TI  - Removal of organic matter from wastewater using M/Al-pillared clays (M = Fe or
      Mn) as coagulants.
AB  - This work is about organic matter removal from Sidi Bel Abbes wastewater plant
      (Algeria) by coagulation on pillared clays (PILCs) under pH and PZC (point of
      zero charge), conditions. Two pillared clays, M/Al-PILCs (M = Fe or Mn), were
      synthesized, characterized, and studied as coagulants. Results showed that Fe/Al
      pillared clay exhibits superior efficiency, with 18% higher removal rate than the
      common coagulants alum (AS) and ferric chloride (FCl), and that sedimentation
      time has positive effect on turbidity removal, with 95.85% removal rate during 30
      min. Moreover PILCs will not cause pH go down too low, which is an advantage for
      achieving the best overall treatment. The IR and UV bands' reduction reveals the
      breakdown fragmentation of high molecular weight organic substances into smaller
      units. The highest total organic carbon (supercritical water oxidation analysis)
      and chemical oxygen demand adsorption capacities (48.52% and 61.85% respectively)
      obtained for Fe/Al-PILC can be related to increased basal spacing between
      adjacent layers, creating favorable adsorption sites in the microporous system.
      The suggested adsorption mechanism involves strong interactions between
      pollutants and PILCs leading to PILC-pollutant complex formation.

PMID- 30207996
TI  - Purification efficiency of zeolite and two planted grasses on sewage and
      relationship with carbon-nitrogen-phosphorus ratios in simulated constructed
      wetland system.
AB  - For achieving the economical and efficient configuration of constructed wetlands
      (CWs), a simulated device of vertical flow CWs was used to investigate the
      effects of different volume ratios of substrates to two cold-resistant plants on
      pollutant concentrations as well as their ratios in effluent under different
      inflow domestic sewage concentrations. The average removal rates (ARRs) of
      ammonia nitrogen, total nitrogen (TN) and total phosphorus were 82.7%, 84.9% and
      80.6% respectively in the treatments with zeolite but no plants, which increased
      by 22.6%, 20.8% and 14.9% compared with those without zeolite and plants.
      However, in the treatments with zeolite and planted grasses, the ARRs of the
      three pollutants were over 90%, and those of chemical oxygen demand were lower.
      The removal rates of ammonia nitrogen, TN and total phosphorus had negative
      correlations with C:N and N:P ratios and positive correlations with the C:P
      ratios. Increasing the ratio of zeolite to soil from 1:1 to 2:1 had no
      significant effects in the removal efficiency. It was suggested that planting
      Lolium perenne or Poa annua on the substrate with a zeolite to soil volume ratio
      of 1:1 could be considered as the optimum combination to purify the domestic
      sewage in north rural areas of China.

PMID- 30207997
TI  - Removal of methylene blue from aqueous solution using sediment obtained from a
      canal in an industrial park.
AB  - Drainage canal sediments in an industrial park are generally dredged to landfill
      in Taiwan. The objective of this study was to evaluate feasibility employing the
      sediment as an adsorbent for removal of dye. The sediment contained approximately
      10% of organic matter and little heavy metals. Infrared (IR) analysis revealed
      that carboxyl was the most important functional group for methylene blue (MB)
      sorption. Canal sediment could remove the most MB from water at pH 8.0 and this
      removal increased with increasing temperature. The MB sorption was well described
      by the Langmuir, Dubinin-Radushkevich, and Temkin sorption isotherms at 10
      degrees C, but it showed good compliance with Freundlich isotherm at 25 degrees C
      and 40 degrees C. The MB adsorption was a spontaneous and endothermic reaction;
      its maximum calculated adsorption capacity (Qm) was 56.0 mg g-1 at 10 degrees C
      by the Langmuir isotherm. The calculated values of enthalpy (DeltaH degrees ) and
      entropy (DeltaS degrees ) are 14.6 kJ mol-1 and 149.2 kJ mol-1, respectively.
      Only pseudo-second-order adsorption kinetic model successfully described the
      kinetics of MB onto the sediment at different operation parameters. Activation
      energy of MB adsorption calculated from Arrhenius equation was 16.434 kJ mol-1,
      indicating the binding between canal sediment and MB was a physical adsorption.

PMID- 30207998
TI  - Effect of kaolin on floc properties for reactive orange removal in continuous
      coagulation process.
AB  - Magnesium hydroxide was used as a coagulant for treating reactive orange
      wastewater in a real continuous process. Effects of kaolin on coagulation
      performance and floc properties were investigated with controlled experiments
      through floc size distribution, zeta potential, scanning electron microscopy and
      Fourier transform infrared spectroscopy. Kaolin had significant influence on
      magnesium hydroxide-reactive orange floc formation and growth. The results showed
      that average floc size reached 16.31, 12.88 and 20.50 MUm, respectively, in the
      rapid mixer, flocculation basin and sedimentation tank when kaolin concentration
      was 10 mg/L and reactive orange initial concentration was 0.25 g/L. The floc size
      tended to increase with the increase of kaolin suspension to 10 mg/L. All of the
      flocs under investigation showed that floc breakage led to decreased average floc
      size and remained stable in the flocculation basin. Reactive orange and kaolin
      could be removed effectively in the continuous coagulation process. Reactive
      orange was adsorbed in the surface of magnesium hydroxide through charge
      neutralization and adsorption.

PMID- 30207999
TI  - An assessment of geo-morphology and hydro-biological factors of major wetlands of
      Bangladesh.
AB  - The present study investigates the geo-morphological features, hydro-biological
      profiles and resource characteristics of some selected wetlands in Brahmanbaria
      district, Bangladesh. Two categories of wetland have been classified on the basis
      of area such as the small category (40-100 ha), which belongs to 11 wetlands and
      the large category (100-200 ha) to nine wetlands. The mean depth of all the
      surveyed wetland does not exceed 3.29 +/- 0.83 m. The mean value of organic
      matter was measured as 7.5 +/- 6.34%. The maximum organic matter was recorded at
      Gagotia beel (24.60%) and the minimum organic matter was recorded at Kajolia beel
      (2.06%). The mean value of organic carbon was measured as 3.93 +/- 3.33%. The
      highest amount of organic carbon was found at Gagotia beel (12.95%) while the
      lowest amount of organic carbon was observed at kajolia beel (1.08%). Soil
      texture indicates the percentage composition of sand, silt and clay in sediment.
      The average concentration of sand, silt and clay was recorded to be 53.31 +/-
      15.32, 17.61 +/- 9.56 and 29.08 +/- 12.87%, respectively. Among the 20 selected
      wetlands examined, 13 were found to be perennial wetlands where water is
      available throughout the year. There was significant difference among different
      wetlands in terms of organic carbon, organic matter, sand, silt and clay (P <
      0.05) as analyzed by One Way Analysis of Variance (SPSS v.22). The sampling
      stations were presented as a map created by GIS (ArcMap v.10.1). This qualitative
      and quantitative assessment will not only provide new information about the geo
      morphological and hydro-biological insights into the wetland but also will
      facilitate the development, management, and conservation of aquatic biodiversity
      in a significant and worthwhile manner.

PMID- 30208000
TI  - Detoxification potential and rehabilitation of activated sludge after shock
      loading of Sofia's wastewater treatment plant 'Kubratovo' with mazut.
AB  - The shock loading of wastewater treatment plants (WWTPs) with toxic pollutants
      remains a critical problem with crucial significance for the technologies. On 5
      November 2014, 30 tons of mazut were emitted in Sofia's WWTP 'Kubratovo', passing
      through equipment and damaging the functioning of the technological modules. The
      rehabilitation of activated sludge (AS) after shock loading as well as the
      development of detoxification activity were investigated. The hydrocarbon index
      of petroleum products, filamentous index (FI), sludge biotic index, sludge volume
      index (SVI), chemical oxygen demand (COD), biochemical oxygen demand (BOD5),
      oxygenases and succinate dehydrogenase activities were analyzed for a period of
      two weeks. The results show that independently from prolonged rehabilitation
      period, AS remained with filamentous bulking (SVI over 200 ml/g and FI over 1.107
      MUm/mg). At the same time, the detoxification potential of the AS was developed.
      Although the morphological and functional structure was still not fully
      recovered, the AS developed two adaptive mechanisms. First, activation of
      shorter, more effective ways for benzene ring cleavage, operated by catechol 2,3
      dioxygenase; second, strong increase of succinate dehydrogenase activity, which
      is consistent with the activation of the degradation of trivial substrates for
      energy generating to overcome the intoxication and synthesis of oxygenases.

PMID- 30208001
TI  - pH-sensitive microfiltration membrane prepared from polyethersulfone grafted with
      poly(itaconic acid) synthesized by simultaneous irradiation in homogeneous phase.
AB  - Poly(itaconic acid) (PIA) was grafted onto polyethersulfone (PES) by
      homogeneously phased gamma-ray irradiation. Kinetic polymerization observed was
      studied by analyzing the effect of irradiation dosages and monomer
      concentrations. Then, a pH-sensitive microfiltration (MF) membrane was prepared
      from these PES-g-PIA polymers with different degrees of grafting under phase
      inversion method. Finally, the contact angles, morphologies, pore sizes,
      deionized water permeability and filtration performance for aqueous polyethylene
      glycols solution of the MF membranes were studied. The results show that grafting
      PIA groups onto PES molecular chains endowed the MF membranes with effective pH
      sensitive properties.

PMID- 30208002
TI  - Process and influencing factors of N removal in grassed paving system by 15N
      tracing analysis.
AB  - The effects of nitrogen (N) transformation and transportation processes under
      different soil pH, plant species and rainfall intervals were studied by using a
      15N isotope tracing technique in a simulated grassed paving system. The results
      showed that the grassed paving systems with three plants including Zoysia
      matrella (Z), Eleusine indica (E) and Liriope graminifolia (L), were effective at
      removing NH4+-N, NO3--N, total nitrogen (TN), and chemical oxygen demand (COD)
      from rainfall runoff. However, there was no significant difference of TN removal
      among these three-plant species and a certain soil pH. The experiment showed that
      when the rainfall interval was 5 days, the grassed paving system could remove
      65.8-76.8% of runoff TN in 17 detention days. The N conversion was dominated by
      soil adsorption, plant uptake, microbial assimilation, and nitrification during 0
      5 d. While the main N reactions were through denitrification and dissimilatory
      nitrate reduction to ammonium during 5-14 d.

PMID- 30208003
TI  - Dynamics simulation of ammonia nitrogen absorption in a rural-urban canal on the
      Northeast China Plain.
AB  - To study dynamic laws of ammonia nitrogen retention in a typical rural-urban
      fringe canal, NaBr was selected as a conservative tracer agent, and NH4Cl as an
      additive nutritive salt to conduct an instantaneously added tracer experiment
      outdoors. On this basis, tracer additions for spiralling curve characterisation
      (TASCC) method and nutritive spiral indexes were used for the quantitative
      depiction of retention dynamics of NH4+-N. The Michaelis-Menten (M-M) model was
      used to simulate absorption dynamic characteristics of NH4+-N. Results showed
      that the variation range of absorption length of NH4+-N under background
      concentration was 93.94-295.54 m with an average value of 177.41 m, the variation
      range of mass transfer coefficient was 0.16-0.38 mm/s with an average value of
      0.26 mm/s, and the variation range of absorption rate was 0.16-0.38 mg/(m2?s)
      with an average value of 0.26 mg/(m2?s). The maximum absorption rate of NH4+-N
      obtained via M-M equation simulation was 0.59-1.38 mg/(m2?s), and the
      subsaturation constant was 1.10-5.03 mg/L. The variability of the dynamic
      absorption length, overall dynamic absorption rate, and overall dynamic mass
      transfer coefficient shown by NH4+-N within the range from background
      concentration to saturation concentration certified that TASCC could analyse the
      dynamic process of NH4+-N retention and absorption by the canal.

PMID- 30208004
TI  - The influence of dissolved oxygen on partial nitritation/anammox performance and
      microbial community of the 200,000 m3/d activated sludge process at the Changi
      water reclamation plant (2011 to 2016).
AB  - Mainstream partial nitritation/anammox (PN/A), coupled with excess biological
      phosphorus removal, in a 200,000 m3/d step-feed activated sludge process (Train
      2) in the Changi Water Reclamation Plant (WRP), Singapore, has been studied and
      reported. This paper presents an overview of process performance and the
      microbial community during the period from 2011 to 2016. The site data showed
      that, along with the reduction of dissolved oxygen (DO) from 1.7 to 1.0 mg O2/L
      in the aeration zones, the concentrations of ammonium and nitrate of the final
      effluent increased, while nitrite decreased, resulting in an increase of 2.4 mg
      N/L of total inorganic nitrogen. Autotrophic nitrogen removal was higher than
      heterotrophic biological nitrogen removal under higher DO concentration
      conditions, but decreased under low DO operating condition. These macro-scale
      changes were caused by shifts of the nitrogen-converting microbial community. The
      ammonia oxidizing bacteria (AOB) population abundance was reduced by 30 times,
      while the nitrite oxidizing bacteria (NOB) population abundance and specific
      activity increased significantly with a shift of dominant genus from Nitrobacter
      to Nitrospira. The ratio of AOB and NOB specific activities were reduced from
      12.8 to 1.6, and the ex situ nitrite accumulation ratio reduced from 76% to 29%.
      Changes in the microbial community and overall process performance illustrated
      that, compared to the excellent NOB suppression under high DO conditions, NOB
      were more active after the DO concentration reduction despite still being partly
      suppressed. This case study demonstrated, for the first time, the influence of DO
      reduction on the nitrogen conversion microbial community and PN/A process
      performance for a suspended growth system. Its relevance to biofilm and hybrid
      PN/A processes is also discussed.

PMID- 30208005
TI  - Microalgae as biological treatment for municipal wastewater - effects on the
      sludge handling in a treatment plant.
AB  - A mix of microalgae and bacteria was cultivated on pre-sedimented municipal
      wastewater in a continuous operated microalgae-activated sludge process. The
      excess material from the process was co-digested with primary sludge in
      mesophilic and thermophilic conditions in semi-continuous mode (5 L digesters).
      Two reference digesters (5 L digesters) fed with waste-activated sludge (WAS) and
      primary sludge were operated in parallel. The methane yield was slightly reduced
      (~10%) when the microalgal-bacterial substrate was used in place of the WAS in
      thermophilic conditions, but remained approximately similar in mesophilic
      conditions. The uptake of heavy metals was higher with the microalgal-bacterial
      substrate in comparison to the WAS, which resulted in higher levels of heavy
      metals in the digestates. The addition of microalgal-bacterial substrate enhanced
      the dewaterability in thermophilic conditions. Finally, excess heat can be
      recovered in both mesophilic and thermophilic conditions.

PMID- 30208006
TI  - Revisiting conceptual stormwater quality models by reconstructing virtual state
      variables.
AB  - This work proposes a Bayesian non-informative reconstruction of virtual state
      variables in the representation of stormwater total suspended solids
      pollutographs by the traditional wash-off models, based on 255 rainfall events
      measured in a 185 ha French urban catchment. Results from event-based analyses
      revealed the missing representation of an essential process in the traditional
      rating curve (RC) model (simplest wash-off model) for 56% of the rainfall events.
      The unsatisfactory performances of the RC model are found to be not necessarily
      linked to antecedent dry weather conditions, as assumed by a great number of
      accumulation/wash-off models. Statistical tests suggest that non-representable
      rainfall events by the RC model are randomly distributed in time. The proposed
      Bayesian reconstructions of a potential process missed by the RC model exhibit a
      suitable identifiability at an intra-event scale. However, these reconstructions
      are not interpretable from the traditional accumulation/wash-off notions, i.e. in
      terms of a unique state of virtual available mass over the catchment that is
      decreasing over time, due to their high unrepeatability regarding their shape and
      their low prediction capacity for other rainfall events.

PMID- 30208007
TI  - Stormwater management in nutrient-sensitive watersheds: a case study
      investigating impervious cover limits and pollutant-load regulations.
AB  - The objective of this research project was to compare two stormwater management
      strategies within a nutrient-sensitive watershed: impervious cover limits versus
      pollutant-load regulations. A case study was conducted in the nutrient-sensitive
      Falls Lake watershed in North Carolina, USA, where a commercial fitness complex
      was constructed in a zone previously restricted to low-density housing. The Falls
      Lake watershed has a stormwater regulation that limits total nitrogen and total
      phosphorus export loads to 2.47 kg/ha/yr and 0.37 kg/ha/yr, respectively.
      Hydrology and water quality were monitored pre- and post-development to quantify
      changes to stormwater volumes, pollutant concentrations, and annual export
      loading rates. On-site stormwater control measures (SCMs) reduced nutrient export
      loading rates below the regulatory standard. However, increased stormwater
      volumes and nutrient export loading rates were observed from pervious surfaces
      that were disturbed during construction (total nitrogen increased from 2.06 to
      4.24 kg/ha/yr, total phosphorus increased from 0.41 to 0.73 kg/ha/yr). Results
      from this case study suggest that (1) impervious cover limits do not adequately
      account for a parcel's nutrient export loads and (2) SCMs that reduce volume and
      treat pollutants can reduce nutrient export loads below regulatory levels in the
      Falls Lake watershed.

PMID- 30208008
TI  - Arsenate removal from aqueous solution using chitosan-coated bentonite, chitosan
      coated kaolinite and chitosan-coated sand: parametric, isotherm and thermodynamic
      studies.
AB  - In the present work, the removal efficiency of As(V) from aqueous solution using
      chitosan-coated bentonite (CCB), chitosan-coated kaolinite (CCK) and chitosan
      coated sand (CCS) was evaluated. The chitosan-based adsorbents were characterized
      using scanning electron microscopy, Fourier-transform infrared spectroscopy, the
      Brunauer-Emmett-Teller method and thermogravimetric analysis. Kinetic studies
      revealed that As(V) uptake using CCB, CCK and CCS fitted well with the pseudo
      second order equation (R2 >= 0.9847; RMSE <= 9.1833). Equilibrium data show good
      correlation with the Langmuir model (R2 >= 0.9753; RMSE <= 8.5123; SSE <=
      16.2651) for all adsorbents, which implies monolayer coverage onto homogenous
      energy sites. The Langmuir adsorption capacity for As(V) at pH 7.0 was determined
      to be 67.11, 64.85, and 16.78 mg/g for CCB, CCK and CCS, respectively.
      Thermodynamic studies show that As(V) uptake is exothermic in nature using CCK
      and endothermic using CCB and CCS. Moreover, adsorption of As(V) was feasible and
      spontaneous for CCB and CCS at 298 to 328 K. Results show that CCB is the most
      effective adsorbent in the removal of As(V) from water due to its high surface
      area and large pore diameter.

PMID- 30208009
TI  - Comprehensive assessment of system performance in a full-scale wastewater
      treatment plant with an anaerobic/anoxic/aerobic membrane bioreactor combined
      with the ozonation process.
AB  - The system performance, economic cost and environmental impact of a full-scale
      anaerobic/anoxic/aerobic/membrane bioreactor (3AMBR) combined with the ozonation
      process were evaluated. The 3AMBR/ozonation process removed biochemical oxygen
      demand (BOD), chemical oxygen demand (COD), suspended solids, NH4-N and total
      phosphorus efficiently, with removal percentages above 94%, while the total
      nitrogen removal percentage was only 70%. The multiple linear regression analysis
      showed that hydraulic retention time (HRT) had a significant effect on nitrogen
      removal. A low HRT benefited nitrogen removal. Ferrous sulfate dosage close to
      the optimal value and a high mixed liquid suspended solid could enhance the
      phosphorus removal. The electricity cost accounted for 88% of the total economic
      costs. Greenhouse gas (GHG) emissions from the BOD oxidation and endogenous decay
      accounted for more than 50% of total emissions. The second largest GHG emission
      source was electricity consumption, accounting for 41%. The key to reduce the
      eutrophication was to enhance nitrogen removal. The composite cost of the
      3AMBR/ozonation process was 251 CNY/t CODeq removed, among which economic cost
      accounted for 82.5%, while environmental impact cost accounted for a small
      proportion.

PMID- 30208010
TI  - Evaluation of two statistical approaches for estimating pollutant loads at
      adjacent combined sewer overflow structures.
AB  - Quantifying pollutant loads from combined sewer overflows (CSOs) is necessary for
      assessing impacts of urban drainage on receiving water bodies. Based on data
      obtained at three adjacent CSO structures in the Louis Fargue catchment in
      Bordeaux, France, this study implements multiple linear regression (MLR) and
      random forest regression (RFR) approaches to develop statistical models for
      estimating emitted loads of total suspended solids (TSS). Comparison between
      hierarchical clustering selection and random selection of CSO events for model
      calibration is included in model development. The results indicate that selection
      of the model's explanatory variables depends on both the type of approach and the
      CSO structure. By using the cluster technique to select representative events for
      model calibration, model predictability is generally improved. For the available
      dataset, MLR may have advantages over RFR in terms of verification performance
      and lower range of error due to splitting events for calibration and
      verification. But RFR model uncertainty bands are considerably narrower than the
      MLR ones.

PMID- 30208011
TI  - Preparation and characterization of chitosan/Fe2O3 nano composite for the
      adsorption of thorium (IV) ion from aqueous solution.
AB  - In this study, novel chitosan/Fe2O3nano composite Ch/Fe-Onc was synthesized and
      evaluated as an adsorbent for removing thorium (IV) (Th4+) ion from aqueous
      solution. The Ch/Fe-Onc was characterized by X-ray diffraction (XRD), Brunauer
      Emmett-Teller (BET), Fourier transform infrared (FTIR) and scanning electron
      microscopy (SEM). Response surface methodology (RSM) was used in the optimization
      of Th4+ adsorption for parameters such as pH, the initial metal ion concentration
      (Th4+ concentration) and contact time. The statistical measures (i.e. analysis of
      variance, R2, the lack of fit test and the P value) specify that the developed
      model is proper. Furthermore, the adsorption kinetics was well defined by the
      pseudo-second-order equation, while the adsorption isotherms were better fitted
      by the Langmuir model. The adsorption capacity of Ch/Fe-Onc was 430 mg Th4+g-1
      composite which leads to 99% removal at 25  degrees C. Moreover, thermodynamic
      parameters which state the natural and endothermic nature of the reactions were
      determined. The loaded Th4+ can be easily regenerated with HNO3 and the Ch/Fe-Onc
      can be used repeatedly without any significant reduction in its adsorption
      capacity. The desorption level of Th4+ from the Ch/Fe-Onc by using 0.1 M HNO3,
      was more than 95%.

PMID- 30208012
TI  - A t(3;8)(q26.2;q24) involving the EVI1 (MECOM) Gene.
AB  - OBJECTIVES: Polycythemia vera (PV) is a Philadelphia chromosome-negative
      myeloproliferative neoplasm (MPN) primarily characterized by increased red blood
      cell production. We report a case of a 68-year-old male with a history of PV.
      About four years later, the patient developed myelofibrosis. A bone marrow biopsy
      confirmed the presence of myelofibrosis confirmed by a hypercellular bone marrow
      (80%) with increased reticulin fibrosis (MF2-3), 5% blasts, and a normal 46,XY
      karyotype. A follow-up bone marrow biopsy documented acute myeloid leukemia (post
      polycythemic myelofibrosis with acute leukemic transformation) with 20-30% blasts
      in the bone marrow. Chromosome analysis revealed an abnormal male karyotype with
      a t(3;8)(q26.2;q23) involving MECOM (EVI1) on 11q23 and confirmed by FISH and no
      PVTI rearrangement. To the best of our knowledge, this translocation has not been
      reported in acute myeloid leukemia (AML), de novo or therapy related
      myelodysplastic syndrome (MDS), or MDS or myeloproliferative disorder progressing
      to AML. However, further studies need to be conducted to elucidate and identify
      the roles of genes other than MECOM involved in this peculiar translocation with
      such a poor prognosis.

PMID- 30208013
TI  - Mistaken identity: A Case for Karyotype Analysis Work-up of Soft Tissue Tumors.
AB  - OBJECTIVES: Soft tissue pathology encompasses a diverse range of benign and
      malignant soft tissue tumors. Definitive diagnosis is challenging due to the vast
      number of histologic subtypes (>100) and the potential for overlapping clinical,
      radiographic, histologic, and/or immunohistochemical features. Many institutions
      have moved away from cytogenetic analysis in the workup of soft tissue tumors;
      however, specific non-random cytogenetic abnormalities are characteristic of
      various tumor types and can reveal or confirm the diagnosis in challenging cases.
      We present a diagnostically challenging case of myxoid liposarcoma initially
      considered to be reactive in nature and only correctly diagnosed when karyotype
      analysis revealed the characteristic t(12;16)(q13;p11.2), thus altering patient
      care and management.

PMID- 30208014
TI  - The Role of miR-15a and miR-16-1 in the Pathogenesis of Chronic Lymphocytic
      Leukemia, and the Importance of microRNAs in Targeted Therapies.
AB  - OBJECTIVES: Chronic lymphocytic leukemia (CLL) is the most common type of
      hematological cancer diagnosed in human adults; however, it has been linked with
      a series of chromosomal abnormalities, the most common being deletion of 13q14.
      This chromosomal alteration leads to the deletion of the miR-15/16 cluster, as
      well as downregulation of DLEU7. Deletion of miR-15a and miR-16-1 causes
      overexpression of BCL2, an apoptosis suppressing protein, while the deletion of
      DLEU7 activates the NF-kB pathway. Both lead to the development of a pro
      proliferative phenotype, an inhibition of apoptosis and prolonged cell life. This
      is the basis of the pathogenesis of indolent CLL where these pathways present
      themselves as essential targets for pharmacological therapy. Since BCL2 is,
      arguably, the most important factor in the pathogenesis of CLL, BCL2 inhibitors
      are beginning to acquire more relevance regarding targeted therapies for patients
      with CLL. Here we review the role of miR-15a and miR-16-1 in the pathogenesis of
      chronic lymphocytic leukemia, and the importance of microRNAs in targeted
      therapies.

PMID- 30208016
TI  - Outcomes of early NIH-funded investigators: Experience of the National Institute
      of Allergy and Infectious Diseases.
AB  - Survival of junior scientists in academic biomedical research is difficult in
      today's highly competitive funding climate. National Institute of Health (NIH)
      data on first-time R01 grantees indicate the rate at which early investigators
      drop out from a NIH-supported research career is most rapid 4 to 5 years from the
      first R01 award. The factors associated with a high risk of dropping out, and
      whether these factors impact all junior investigators equally, are unclear. We
      identified a cohort of 1,496 investigators who received their first R01
      equivalent (R01-e) awards from the National Institute of Allergy and Infectious
      Diseases between 2003 and 2010, and studied all their subsequent NIH grant
      applications through 2016. Ultimately, 57% of the cohort were successful in
      obtaining new R01-e funding, despite highly competitive conditions. Among those
      investigators who failed to compete successfully for new funding (43%), the
      average time to dropping out was 5 years. Investigators who successfully obtained
      new grants showed remarkable within-person consistency across multiple grant
      submission behaviors, including submitting more applications per year, more
      renewal applications, and more applications to multiple NIH Institutes. Funded
      investigators appeared to have two advantages over their unfunded peers at the
      outset: they had better scores on their first R01-e grants and they demonstrated
      an early ability to write applications that would be scored, not triaged. The
      cohort rapidly segregated into two very different groups on the basis of PI
      consistency in the quality and frequency of applications submitted after their
      first R01-e award. Lastly, we identified a number of specific demographic
      factors, intitutional characteristics, and grant submission behaviors that were
      associated with successful outcomes, and assessed their predictive value and
      relative importance for the likelihood of obtaining additional NIH funding.

PMID- 30208015
TI  - Anterior Cervical Corpectomy and Fusion and Anterior Cervical Discectomy and
      Fusion Using Titanium Mesh Cages for Treatment of Degenerative Cervical
      Pathologies: A Literature Review.
AB  - Anterior cervical corpectomy and fusion (ACCF) and anterior cervical discectomy
      and fusion (ACDF) are 2 effective and safe surgical treatments of degenerative
      cervical pathologies and are associated with a high percentage of excellent
      clinical outcomes when a graft or device must be used during the surgery, such as
      an allograft, autograft, nano-hydroxyapatite/polyamide cages, poly-ether-ether
      ketone (PEEK) cages, and titanium mesh cages (TMCs). Although TMCs have been used
      in cervical surgeries for almost 2 decades, no specific reviews have been
      performed introducing the state of this material. Thus, in the present review, we
      discuss the status of using TMCs in anterior cervical surgeries. Studies that
      tested the usage of TMCs in treating degenerative cervical pathologies were
      included in this review. The development and progress of TMCs, the biomechanical
      analysis of TMCs, the radiological and clinical assessment of TMCs, the
      advantages and disadvantages of using TMCs, and their prospects for future
      applications as a device of ACCF and ACDF in treating degenerative cervical
      pathologies are discussed. Studies included in this review showed that TMCs can
      provide sufficient biomechanical stability. Furthermore, the TMCs used in
      anterior cervical fusion avoid the donor-site morbidity and achieve a solid bony
      fusion. However, there are some shortcomings. The structural characteristics and
      the design of TMCs cause the TMC subsidence rate to remain high, thus resulting
      in multiple related complications. We believe that due to the virtues of TMCs,
      they are worthy of application and promotion. However, the structure of TMCs
      should be further optimized to reduce the TMC subsidence rate and subsidence
      related complications, ultimately achieving excellent clinical results.

PMID- 30208018
TI  - A cautionary note for claims about the microbiome's impact on the "self".

PMID- 30208017
TI  - Distribution and breeding sites of Aedes aegypti and Aedes albopictus in 32
      urban/peri-urban districts of Mozambique: implication for assessing the risk of
      arbovirus outbreaks.
AB  - BACKGROUND: Aedes-borne arboviruses have emerged as an important public health
      problem worldwide and, in Mozambique, the number of cases and its geographical
      spread have been growing. However, information on the occurrence, distribution
      and ecology of Aedes aegypti and Ae. albopictus mosquitoes remain poorly known in
      the country. METHODS: Between March and April 2016, a cross-sectional study was
      conducted in 32 districts in Mozambique to determine the distribution and
      breeding sites of Ae. aegypti and Ae. albopictus. Larvae and pupae were collected
      from a total of 2,807 water-holding containers using pipette, dipper, funnel and
      sweeping procedures, depending on the container type and location. Both outdoor
      and indoor water-holding containers were inspected. The immature forms were
      reared to adults and the identifications of the mosquito species was carried out
      with a stereomicroscope using a taxonomic key. RESULTS: Aedes aegypti was found
      in every district sampled, while Ae. albopictus was only found in Moatize
      district, situated in Tete Province in the central part of the country. Six
      hundred and twenty-eight of 2,807 (22.4%) containers were positive for Ae.
      aegypti but only one (0.03%) was positive for Ae. albopictus. The Container Index
      (CI) of Aedes was highest in densely populated suburban areas of the central
      region (260/604; 43.0%), followed by suburban areas in northern areas (228/617;
      36.9%) whilst the lowest proportion was found in urbanized southern areas
      (140/1586; 8.8%). The highest CI of Aedes was found in used tires (448/1268;
      35.3%), cement tanks (20/62; 32.3%) and drums (21/95; 22.1%). CONCLUSION: Data
      from our study showed that Ae. aegypti is present nation-wide, since it occurred
      in every sampled district, whilst Ae. albopictus had a limited distribution.
      Therefore, the risk of transmission of dengue and chikungunya is likely to have
      been underestimated in Mozambique. This study highlights the need for the
      establishment of a national entomological surveillance program for Aedes spp. in
      Mozambique in order to gain a better understanding about vector bionomics and to
      support the development of informed effective vector control strategies.

PMID- 30208019
TI  - Social acceptance and perceived ecosystem services of urban agriculture in
      Southern Europe: The case of Bologna, Italy.
AB  - Urban agriculture has become a common form of urban land use in European cities
      linked to multiple environmental, social and economic benefits, as well as to
      diversified forms (from self-production allotments to high-tech companies).
      Social acceptance will determine the development of urban agriculture and
      specific knowledge on citizens' perception is required in order to set the basis
      for policy-making and planning. The ecosystem services provided by urban
      agriculture can be determinant in this process. The goal of this paper is to
      evaluate the social acceptance and the perceived ecosystem services of urban
      agriculture in the city of Bologna (Italy), as an example of a Southern European
      city. In particular, we evaluated the preferences for urban land uses, for
      different typologies of urban agriculture and for the resulting products, the
      perceived provision of ecosystem services and the willingness to engage in new
      initiatives. A survey that investigated these topics (including open questions,
      closed questions and Likert-scale evaluation) was performed on the citizens of
      Bologna (n = 380) between October and November 2016. Results showed that urban
      agriculture is widely accepted by the inhabitants of Bologna, particularly
      regarding vegetable production. Although intensive farming systems were the least
      preferred forms to be implemented in Bologna, citizens highly accepted a large
      variety of urban agriculture goods, with preference for those obtained from
      plants as compared to animal products. The willingness-to-pay for urban food
      products was mostly the same as for conventional ones, although the participants
      recognised the social values, proximity and quality of the former. Socio-cultural
      ecosystem services were perceived as more valuable than environmental ones.
      Policy-making recommendations can be extracted from the results to facilitate the
      development of urban agriculture plans and policies.

PMID- 30208020
TI  - Hybridization in bottlenose dolphins-A case study of Tursiops aduncus * T.
      truncatus hybrids and successful backcross hybridization events.
AB  - The bottlenose dolphin, genus Tursiops is one of the best studied of all the
      Cetacea with a minimum of two species widely recognised. Common bottlenose
      dolphins (T. truncatus), are the cetacean species most frequently held in
      captivity and are known to hybridize with species from at least 6 different
      genera. In this study, we document several intra-generic hybridization events
      between T. truncatus and T. aduncus held in captivity. We demonstrate that the F1
      hybrids are fertile and can backcross producing apparently healthy offspring,
      thereby showing introgressive inter-specific hybridization within the genus. We
      document that female F1 hybrids can reach sexual maturity at 4 yr and 3 mo of
      age, and can become pregnant and give birth before being fully weaned. The
      information presented has implications for understanding hybrid reticulation
      among cetacean species and practical implications for captive facilities housing
      either Tursiops species or hybrids thereof.

PMID- 30208021
TI  - Transcription factor CBF-1 is critical for circadian gene expression by
      modulating WHITE COLLAR complex recruitment to the frq locus.
AB  - Transcription of the Neurospora crassa circadian clock gene frequency (frq) is an
      essential process in the negative feedback loop that controls circadian rhythms.
      WHITE COLLAR 1 (WC-1) and WHITE COLLAR 2 (WC-2) forms the WC complex (WCC) that
      is the main activator of frq transcription by binding to its promoter. Here, we
      show that Centromere Binding Factor 1 (CBF-1) is a critical component of the N.
      crassa circadian clock by regulating frq transcription. Deletion of cbf-1
      resulted in long period and low amplitude rhythms, whereas overexpression of CBF
      1 abolished the circadian rhythms. Loss of CBF-1 resulted in WC-independent FRQ
      expression and suppression of WCC activity. As WCC, CBF-1 also binds to the C-box
      at the frq promoter. Overexpression of CBF-1 impaired WCC binding to the C-box to
      suppress frq transcription. Together, our results suggest that the proper level
      of CBF-1 is critical for circadian clock function by suppressing WC-independent
      FRQ expression and by regulating WCC binding to the frq promoter.

PMID- 30208023
TI  - Stereotyping across intersections of race and age: Racial stereotyping among
      White adults working with children.
AB  - This study examined the prevalence of racial/ethnic stereotypes among White
      adults who work or volunteer with children, and whether stereotyping of
      racial/ethnic groups varied towards different age groups. Participants were 1022
      White adults who volunteer and/or work with children in the United States who
      completed a cross-sectional, online survey. Results indicate high proportions of
      adults who work or volunteer with children endorsed negative stereotypes towards
      Blacks and other ethnic minorities. Respondents were most likely to endorse
      negative stereotypes towards Blacks, and least likely towards Asians (relative to
      Whites). Moreover, endorsement of negative stereotypes by race was moderated by
      target age. Stereotypes were often lower towards young children but higher
      towards teens.

PMID- 30208025
TI  - The microbiome and the human: A reply to Parke and colleagues.

PMID- 30208022
TI  - Protein kinase A negatively regulates Ca2+ signalling in Toxoplasma gondii.
AB  - The phylum Apicomplexa comprises a group of obligate intracellular parasites that
      alternate between intracellular replicating stages and actively motile
      extracellular forms that move through tissue. Parasite cytosolic Ca2+ signalling
      activates motility, but how this is switched off after invasion is complete to
      allow for replication to begin is not understood. Here, we show that the cyclic
      adenosine monophosphate (cAMP)-dependent protein kinase A catalytic subunit 1
      (PKAc1) of Toxoplasma is responsible for suppression of Ca2+ signalling upon host
      cell invasion. We demonstrate that PKAc1 is sequestered to the parasite periphery
      by dual acylation of PKA regulatory subunit 1 (PKAr1). Upon genetic depletion of
      PKAc1 we show that newly invaded parasites exit host cells shortly thereafter, in
      a perforin-like protein 1 (PLP-1)-dependent fashion. Furthermore, we demonstrate
      that loss of PKAc1 prevents rapid down-regulation of cytosolic [Ca2+] levels
      shortly after invasion. We also provide evidence that loss of PKAc1 sensitises
      parasites to cyclic GMP (cGMP)-induced Ca2+ signalling, thus demonstrating a
      functional link between cAMP and these other signalling modalities. Together,
      this work provides a new paradigm in understanding how Toxoplasma and related
      apicomplexan parasites regulate infectivity.

PMID- 30208024
TI  - A comparative analysis of label-free liquid chromatography-mass spectrometry
      liver proteomic profiles highlights metabolic differences between pig breeds.
AB  - The liver is a complex organ governing several physiological processes that
      define biological mechanisms affecting growth, feed efficiency and performance
      traits in all livestock species, including pig. Proteomics may contribute to a
      better understanding of the relationship between liver functions and complex
      production traits in pigs and to characterize this species as biomedical model.
      This study applied, for the first time, a label-free liquid chromatography-mass
      spectrometry (LC-MS) proteomic approach to compare the liver proteome profiles of
      two important heavy pig breeds, Italian Duroc and Italian Large White. Liver
      specimens were collected (after slaughtering) from performance tested pigs of
      these two breeds, raised in standard conditions. The label-free LC-MS method
      captured a total of 501 proteins of which 200 were subsequently considered in the
      between breeds comparison. A statistical pipeline based on the sparse Partial
      Least Squares Discriminant Analysis (sPLS-DA), coupled with stability and
      significance tests, was applied for the identification of up or down regulated
      proteins between breeds. This analysis revealed a total of 25 proteins clearly
      separating Italian Duroc and Italian Large White pigs. Among the top proteins
      differentiating the two breeds, 3-ketoacyl-CoA thiolase, mitochondrial (ACAA2)
      and histone H2B type 2-F (HIST2H2BF) were up-regulated in Italian Duroc pigs and
      carboxylesterase 3 (CES3) and ketohexokinase (KHK) were up-regulated in Italian
      Large White pigs. Fatty acid synthase (FASN), involved in fatty acid metabolism
      and encoded by a gene located in a QTL region for fatty acid composition, was up
      regulated in Italian Large White pigs. The in silico protein interaction analysis
      showed that 16 of these proteins were connected in one big module. Bioinformatic
      functional analysis indicated that differentially expressed proteins were
      involved in several biological processes related to the metabolism of lipids,
      amino-acids, carbohydrates, cofactors and antibiotics/drugs, suggesting that
      these functions might distinguish Italian Duroc and Italian Large White pigs.
      This pilot comparative proteomic analysis of the porcine liver highlighted
      several biological factors that could determine the peculiar production
      potentials of these two heavy pig breeds, derived by their different genetic
      backgrounds.

PMID- 30208026
TI  - Lso2 is a conserved ribosome-bound protein required for translational recovery in
      yeast.
AB  - Ribosome-binding proteins function broadly in protein synthesis, gene regulation,
      and cellular homeostasis, but the complete complement of functional ribosome
      bound proteins remains unknown. Using quantitative mass spectrometry, we
      identified late-annotated short open reading frame 2 (Lso2) as a ribosome
      associated protein that is broadly conserved in eukaryotes. Genome-wide
      crosslinking and immunoprecipitation of Lso2 and its human ortholog coiled-coil
      domain containing 124 (CCDC124) recovered 25S ribosomal RNA in a region near the
      A site that overlaps the GTPase activation center. Consistent with this location,
      Lso2 also crosslinked to most tRNAs. Ribosome profiling of yeast lacking LSO2
      (lso2Delta) revealed global translation defects during recovery from stationary
      phase with translation of most genes reduced more than 4-fold. Ribosomes
      accumulated at start codons, were depleted from stop codons, and showed codon
      specific changes in occupancy in lso2Delta. These defects, and the conservation
      of the specific ribosome-binding activity of Lso2/CCDC124, indicate broadly
      important functions in translation and physiology.

PMID- 30208027
TI  - Selective ion permeation involves complexation with carboxylates and lysine in a
      model human sodium channel.
AB  - Bacterial and human voltage-gated sodium channels (Navs) exhibit similar cation
      selectivity, despite their distinct EEEE and DEKA selectivity filter signature
      sequences. Recent high-resolution structures for bacterial Navs have allowed us
      to learn about ion conduction mechanisms in these simpler homo-tetrameric
      channels, but our understanding of the function of their mammalian counterparts
      remains limited. To probe these conduction mechanisms, a model of the human
      Nav1.2 channel has been constructed by grafting residues of its selectivity
      filter and external vestibular region onto the bacterial NavRh channel with
      atomic-resolution structure. Multi-MUs fully atomistic simulations capture long
      time-scale ion and protein movements associated with the permeation of Na+ and K+
      ions, and their differences. We observe a Na+ ion knock-on conduction mechanism
      facilitated by low energy multi-carboxylate/multi-Na+ complexes, akin to the
      bacterial channels. These complexes involve both the DEKA and vestibular EEDD
      rings, acting to draw multiple Na+ into the selectivity filter and promote
      permeation. When the DEKA ring lysine is protonated, we observe that its ammonium
      group is actively participating in Na+ permeation, presuming the role of another
      ion. It participates in the formation of a stable complex involving carboxylates
      that collectively bind both Na+ and the Lys ammonium group in a high-field
      strength site, permitting pass-by translocation of Na+. In contrast, multiple K+
      ion complexes with the DEKA and EEDD rings are disfavored by up to 8.3 kcal/mol,
      with the K+-lysine-carboxylate complex non-existent. As a result, lysine acts as
      an electrostatic plug that partially blocks the flow of K+ ions, which must
      instead wait for isomerization of lysine downward to clear the path for K+
      passage. These distinct mechanisms give us insight into the nature of ion
      conduction and selectivity in human Nav channels, while uncovering high field
      strength carboxylate binding complexes that define the more general phenomenon of
      Na+-selective ion transport in nature.

PMID- 30208028
TI  - Vocal practice regulates singing activity-dependent genes underlying age
      independent vocal learning in songbirds.
AB  - The development of highly complex vocal skill, like human language and bird
      songs, is underlain by learning. Vocal learning, even when occurring in
      adulthood, is thought to largely depend on a sensitive/critical period during
      postnatal development, and learned vocal patterns emerge gradually as the long
      term consequence of vocal practice during this critical period. In this scenario,
      it is presumed that the effect of vocal practice is thus mainly limited by the
      intrinsic timing of age-dependent maturation factors that close the critical
      period and reduce neural plasticity. However, an alternative, as-yet untested
      hypothesis is that vocal practice itself, independently of age, regulates vocal
      learning plasticity. Here, we explicitly discriminate between the influences of
      age and vocal practice using a songbird model system. We prevented zebra finches
      from singing during the critical period of sensorimotor learning by reversible
      postural manipulation. This enabled to us to separate lifelong vocal experience
      from the effects of age. The singing-prevented birds produced juvenile-like
      immature song and retained sufficient ability to acquire a tutored song even at
      adulthood when allowed to sing freely. Genome-wide gene expression network
      analysis revealed that this adult vocal plasticity was accompanied by an intense
      induction of singing activity-dependent genes, similar to that observed in
      juvenile birds, rather than of age-dependent genes. The transcriptional changes
      of activity-dependent genes occurred in the vocal motor robust nucleus of the
      arcopallium (RA) projection neurons that play a critical role in the production
      of song phonology. These gene expression changes were accompanied by
      neuroanatomical changes: dendritic spine pruning in RA projection neurons. These
      results show that self-motivated practice itself changes the expression dynamics
      of activity-dependent genes associated with vocal learning plasticity and that
      this process is not tightly linked to age-dependent maturational factors.

PMID- 30208029
TI  - Genetic ablation of interacting with Spt6 (Iws1) causes early embryonic
      lethality.
AB  - IWS1 is an RNA-polymerase II (RNAPII)-associated transcription elongation factor
      whose biological functions are poorly characterized. To shed some light on the
      function of this protein at the organismal level, we performed a systematic
      tissue analysis of its expression and generated Iws1-deficient mice. A thorough
      immunohistochemical characterization shows that IWS1 protein is present in the
      nucleus of all cells in most of the examined tissues, with few notable
      exceptions. We also report that ablation of Iws1 consistently causes lethality at
      the pre-implantation stage with high expression of the gene in fertilized
      oocytes. In summary, we are providing evidence that Iws1 is expressed in all
      adult organs and it is an essential gene for mouse embryonic development.

PMID- 30208030
TI  - The impact of marine recreational fishing on key fish stocks in European waters.
AB  - Marine recreational fishing (MRF) has been shown to substantially contribute to
      fishing mortality of marine fish. However, European MRF catches are only
      quantified for a small number of stocks, so it is unclear whether a significant
      part of fishing mortality is excluded from stock assessments. This study
      estimated: (i) European MRF removals, which were defined as landings plus dead
      releases; and (ii) impact at stock level by comparing the percentage contribution
      to total removal by MRF and commercial fishing. As MRF data were limited for some
      European countries, catches were reconstructed using a mixture of average release
      proportions, average fish weights, and extrapolation using the catch per fisher
      of the nearest country providing catch estimates. Where catch reconstructions
      exceeded 50%, data were excluded from further analysis. Furthermore, as MRF
      survey methodology can be variable, semi-quantitative estimates of bias and error
      were calculated for each stock. Only 10 of the 20 stocks assessed in this study
      had sufficient MRF data for full reliable estimates. Percentage contribution to
      total removals (MRF + commercial removals) by MRF ranged between 2% for Atlantic
      mackerel in the North Sea and Skagerrak and 43% for Atlantic pollack in the
      Celtic Seas and English Channel. The biomass removed ranged between 297 (+/- 116)
      tonnes (Atlantic cod in the western English Channel and southern Celtic seas) and
      4820 (+/- 1889) tonnes (Atlantic mackerel in the North Sea and Skagerrak), but
      the errors were substantial. Additionally, the bias in the estimated removals was
      low for most stocks, with some positive biases found. The present study indicates
      that removals by MRF can represent a high proportion of the total removals for
      some European marine fish stocks, so inclusion in stock assessments should be
      routine. To achieve this, regular surveys of MRF are required to collect data
      essential for stock assessments.

PMID- 30208031
TI  - Simulating impacts of rapid forest loss on population size, connectivity and
      genetic diversity of Sunda clouded leopards (Neofelis diardi) in Borneo.
AB  - Habitat loss is the greatest threat to biodiversity in Borneo, and to anticipate
      and combat its effects it is important to predict the pattern of loss and its
      consequences. Borneo is a region of extremely high biodiversity from which forest
      is being lost faster than in any other. The little-known Sunda clouded leopard
      (Neofelis diardi) is the top predator in Borneo and is likely to depend
      critically on habitat connectivity that is currently being rapidly lost to
      deforestation. We modeled the effects of landscape fragmentation on population
      size, genetic diversity and population connectivity for the Sunda clouded leopard
      across the entirety of Borneo. We modelled the impacts of land use change between
      the years 2000, 2010 and projected forwards to 2020. We found substantial
      reductions across all metrics between 2000 and 2010: the proportion of landscape
      connected by dispersal fell by approximately 12.5% and the largest patch size
      declined by around 15.1%, leading to a predicted 11.4% decline in clouded leopard
      numbers. We also predict that these trends will accelerate greatly towards 2020,
      with the percentage of the landscape being connected by dispersal falling by
      about 57.8%, the largest patch size falling by around 62.8% and the predicted
      clouded leopard population falling by 62.5% between 2010 and 2020. We predicted
      that these large declines in clouded leopard population size and connectivity
      will also substantially reduce the genetic diversity of the remaining clouded
      leopard population.

PMID- 30208032
TI  - Contact tracing performance during the Ebola epidemic in Liberia, 2014-2015.
AB  - BACKGROUND: During the Ebola virus disease (EVD) epidemic in Liberia, contact
      tracing was implemented to rapidly detect new cases and prevent further
      transmission. We describe the scope and characteristics of contact tracing in
      Liberia and assess its performance during the 2014-2015 EVD epidemic.
      METHODOLOGY/PRINCIPAL FINDINGS: We performed a retrospective descriptive analysis
      of data collection forms for contact tracing conducted in six counties during
      June 2014-July 2015. EVD case counts from situation reports in the same counties
      were used to assess contact tracing coverage and sensitivity. Contacts who
      presented with symptoms and/or died, and monitoring was stopped, were classified
      as "potential cases". Positive predictive value (PPV) was defined as the
      proportion of traced contacts who were identified as potential cases. Bivariate
      and multivariate logistic regression models were used to identify characteristics
      among potential cases. We analyzed 25,830 contact tracing records for contacts
      who had monitoring initiated or were last exposed between June 4, 2014 and July
      13, 2015. Contact tracing was initiated for 26.7% of total EVD cases and detected
      3.6% of all new cases during this period. Eighty-eight percent of contacts
      completed monitoring, and 334 contacts were identified as potential cases (PPV =
      1.4%). Potential cases were more likely to be detected early in the outbreak;
      hail from rural areas; report multiple exposures and symptoms; have household
      contact or direct bodily or fluid contact; and report nausea, fever, or weakness
      compared to contacts who completed monitoring. CONCLUSIONS/SIGNIFICANCE: Contact
      tracing was a critical intervention in Liberia and represented one of the largest
      contact tracing efforts during an epidemic in history. While there were notable
      improvements in implementation over time, these data suggest there were
      limitations to its performance-particularly in urban districts and during peak
      transmission. Recommendations for improving performance include integrated
      surveillance, decentralized management of multidisciplinary teams, comprehensive
      protocols, and community-led strategies.

PMID- 30208033
TI  - Emergent conservation conflicts in the Galapagos Islands: Human-giant tortoise
      interactions in the rural area of Santa Cruz Island.
AB  - The conservation of biodiverse areas around the world has contributed to the
      protection and recovery of endangered species. This has been the case for 11
      species of Galapagos giant tortoises (Chelonoidis spp.) that today are
      successfully maintained over six islands: Espanola, Santiago, Pinzon, Isabela,
      San Cristobal and Santa Cruz. A favourable state of conservation will depend
      however on future development in the islands. In Santa Cruz Island the
      development of the agricultural areas has encroached on the migratory routes of
      the southwestern species C. porteri and may be an emergent conflict for tortoise
      conservation. We investigated the social and ecological inter-linkages using two
      methods framed under a participatory rural appraisal (PRA) approach: semi
      structured interviews and questionnaires to study farmers' perceptions and
      attitudinal factors regarding giant tortoises; as well as the associated socio
      economic impacts of the conflict. Moreover, we coupled the PRA approach with an
      ecological assessment of giant tortoises' population density by performing
      transect counts during the two yearly phases of giant tortoises' migration to the
      lowlands (January to June) and back to the highlands (July to December). Our
      results indicate that farmers reporting damage and cultivating crops have higher
      odds of taking actions (fencing and physical actions) towards giant tortoises;
      regardless of having (or not) a negative perception towards the species. The
      economic losses for crops and fences averaged 2.8 USD/m2 and 13USD/m,
      respectively, and provide an initial step to further analyse and characterise the
      direct and indirect damage costs. Finally, we estimated a density of 76 and 185
      individuals of giant tortoises per km2 in the rural area for the lowland and
      highland migratory phases, respectively. Our approach provides grounded
      scientific social and ecological information to effectively inform and aid
      managers, policy and decision makers in the selection of adequate social and
      ecological criteria to implement the best available options in the resolution of
      this emergent conservation conflict.

PMID- 30208034
TI  - Isometamidium chloride and homidium chloride fail to cure mice infected with
      Ethiopian Trypanosoma evansi type A and B.
AB  - BACKGROUND: Trypanosoma evansi is mechanically transmitted by biting flies and
      affects camels, equines, and other domestic and wild animals in which it causes a
      disease called surra. At least two types of Trypanosoma evansi circulate in
      Ethiopia: type A, which is present in Africa, Latin America and Asia, and type B,
      which is prevalent in Eastern Africa. Currently, no information is available
      about the drug sensitivity of any Ethiopian T. evansi type. METHODOLOGY/PRINCIPAL
      FINDINGS: This study was conducted with the objective of determining the in vivo
      drug sensitivity of two T. evansi type A and two type B stocks that were isolated
      from camels from the Tigray and Afar regions of Northern Ethiopia. We
      investigated the efficacy of four trypanocidal drugs to cure T. evansi infected
      mice: melarsamine hydrochloride (Cymelarsan), diminazene diaceturate (Veriben and
      Sequzene), isometamidium chloride (Veridium) and homidium chloride (Bovidium).
      Per experimental group, 6 mice were inoculated intraperitoneally with
      trypanosomes, treated at first peak parasitemia by daily drug injections for 4
      consecutive days and followed-up for 60 days. Cymelarsan at 2 mg/kg and Veriben
      at 20 mg/kg cured all mice infected with any T. evansi stock, while Sequzene at
      20 mg/kg caused relapses in all T. evansi stocks. In contrast, Veridium and
      Bovidium at 1 mg/kg failed to cure any T. evansi infection in mice.
      CONCLUSIONS/SIGNIFICANCE: We conclude that mice infected with Ethiopian T. evansi
      can be cured with Cymelarsan and Veriben regardless of T. evansi type. In
      contrast, Veridium and Bovidium are not efficacious to cure any T. evansi type.
      Although innate resistance to phenanthridines was previously described for T.
      evansi type A, this report is the first study to show that this phenomenom also
      occurs in T. evansi type B infections.

PMID- 30208035
TI  - The respiratory physiome: Clustering based on a comprehensive lung function
      assessment in patients with COPD.
AB  - BACKGROUND: While spirometry and particularly airflow limitation is still
      considered as an important tool in therapeutic decision making, it poorly
      reflects the heterogeneity of respiratory impairment in chronic obstructive
      pulmonary disease (COPD). The aims of this study were to identify
      pathophysiological clusters in COPD based on an integrated set of standard lung
      function attributes and to investigate whether these clusters can predict patient
      related outcomes and differ in clinical characteristics. METHODS: Clinically
      stable COPD patients referred for pulmonary rehabilitation underwent an
      integrated assessment including clinical characteristics, dyspnea score, exercise
      performance, mood and health status, and lung function measurements (post
      bronchodilator spirometry, body plethysmography, diffusing capacity, mouth
      pressures and arterial blood gases). Self-organizing maps were used to generate
      lung function based clusters. RESULTS: Clustering of lung function attributes of
      518 patients with mild to very severe COPD identified seven different lung
      function clusters. Cluster 1 includes patients with better lung function
      attributes compared to the other clusters. Airflow limitation is attenuated in
      clusters 1 to 4 but more pronounced in clusters 5 to 7. Static hyperinflation is
      more dominant in clusters 5 to 7. A different pattern occurs for carbon monoxide
      diffusing capacity, mouth pressures and for arterial blood gases. Related to the
      different lung function profiles, clusters 1 and 4 demonstrate the best
      functional performance and health status while this is worst for clusters 6 and
      7. All clusters show differences in dyspnea score, proportion of men/women, age,
      number of exacerbations and hospitalizations, proportion of patients using long
      term oxygen and number of comorbidities. CONCLUSION: Based on an integrated
      assessment of lung function variables, seven pathophysiological clusters can be
      identified in COPD patients. These clusters poorly predict functional performance
      and health status.

PMID- 30208036
TI  - Nutrient evaluation of a pork by-product and its use as environmental enrichment
      for managed large exotic cats.
AB  - North American zoological institutions typically feed ground raw meat diets to
      large exotic cats. These diets typically are nutritionally complete, but lack
      physical properties characteristic of whole prey. Lack of mastication and prey
      manipulation may contribute to behavioral and health challenges. Pork by-products
      may provide environmental enrichment to mitigate these challenges. The objectives
      of this study were to evaluate a pig head for nutritional composition and to
      determine if a pig head was biologically relevant environmental enrichment for
      managed large exotic cats. Pig heads consisted of: DM: 48.5%; OM: 60.7%; CP:
      38.4%; fat: 22.0%; CF: 13.5%; TDF: 3.4%; GE: 4.1 kcal/g DM. Five individually
      housed exotic cats (Panthera tigris tigris, Panthera tigris altaica (n = 2),
      Panthera tigris jacksoni, Panthera leo) were observed in 2-h blocks, 24-h before
      pig head introduction (Baseline), at time of pig head introduction (Enrichment)
      and immediately after the pig head was removed (Post Enrichment) via
      instantaneous scan sampling for 4 consecutive weeks. Active behaviors were 55.7%
      higher on Enrichment compared to Baseline days, and 26.4% higher compared to Post
      Enrichment days (p<0.0001). Active behaviors were 39.8% higher on Post Enrichment
      compared to Baseline days (p<0.0001). Total active behaviors were highest
      (p<0.0001) in week 3 and lowest (p<0.0001) in week 4 with differences as high as
      64.5% seen among weeks. In conclusion, pig heads have potential to provide
      nutrient dense enrichment to large exotic cats, and employing a pig head as
      environmental enrichment increased active behaviors and did not lose novelty.

PMID- 30208037
TI  - Implementing active community-based surveillance-response system for Buruli ulcer
      early case detection and management in Ghana.
AB  - BACKGROUND: Buruli Ulcer (BU) is one of the most neglected debilitating tropical
      diseases caused by Mycobacterium ulcerans, which causes considerable morbidity
      and disability. Building on earlier findings that community-based interventions
      could enhance case detection and reduce treatment dropout and defaulter rates, we
      established an active surveillance-response system in an endemic sub-district in
      the Ga West municipality of Ghana to enhance early case detection, diagnosis and
      treatment to reduce or eliminate severe ulcers and its related disabilities.
      METHODS: We established surveillance response system, implemented in
      collaboration with the sub-district disease control officers, selected clinical
      staff and trained community-based volunteers. The active community-based
      surveillance- response system was implemented for 12 months. Also, pre and post
      intervention surveys were conducted to document any change in perceptions on BU
      in the study population over the period. The baseline and endline surveys were
      conducted in August 2016 and August 2017 respectively. RESULTS: On average, each
      person was seen 11 times in 12 months. In all 75 skin lesions were detected
      during surveillance rounds, out of which 17 were suspected to be BU and 12 out of
      the 17 were confirmed as BU using Polymerase chain reaction (PCR). Out of the 12,
      five, three and four were categories I, II and III lesions respectively. Physical
      examination was done on 94% of the people seen during the surveillance rounds.
      Knowledge on BU has also increased in the communities at the end of the study.
      CONCLUSION: The findings from this study have demonstrated that it is possible to
      establish surveillance-response system for BU and by extension, other neglected
      tropical diseases to enhance control and elimination efforts through the use of
      community-based volunteers.

PMID- 30208038
TI  - Lipid production via simultaneous conversion of glucose and xylose by a novel
      yeast, Cystobasidium iriomotense.
AB  - The yeast strains IPM32-16, ISM28-8sT, and IPM46-17, isolated from plant and soil
      samples from Iriomote Island, Japan, were explored in terms of lipid production
      during growth in a mixture of glucose and xylose. Phylogenetically, the strains
      were most closely related to Cystobasidium slooffiae, based on the sequences of
      the ITS regions and the D1/D2 domain of the LSU rRNA gene. The strains were
      oleaginous, accumulating lipids to levels > 20% dry cell weight. Moreover,
      kinetic analysis of the sugar-to-lipid conversion of a 1:1 glucose/xylose mixture
      showed that the strains consumed the two sugars simultaneously. IPM46-17 attained
      the highest lipid content (33%), mostly C16 and C18 fatty acids. Thus, the yeasts
      efficiently converted lignocellulosic sugars to lipids, aiding in biofuel
      production (which benefits the environment, promotes rural jobs, and strengthens
      fuel security). The strains constituted a novel species of Cystobasidium, for
      which we propose the name Cystobasidium iriomotense (type strain ISM28-8sT = JCM
      24594T = CBS 15015T).

PMID- 30208039
TI  - Assessment of problem solving ability in novice programmers.
AB  - Problem Solving (PS) skills allow students to handle problems within an
      educational context. PS is a core competence of Computer Science education and
      affects programming success. In this vein, this paper aims to investigate PS
      ability performance in primary school pupils of a computer course, implemented
      according to the Neo-Piagetian theory of cognitive development. The study
      included 945 Slovenian pupils, ranging from fourth to sixth grade. The effects of
      gender, age and consecutive years of attending the course were examined on
      pupils' PS ability at the pre-operational and concrete operational stages. Pupils
      completed a survey questionnaire with four types of tasks (a series of
      statements, if-statements, loops and variables) at both stages. The analysis
      revealed three findings: the performance of PS ability in all tasks was, at the
      pre-operational stage, associated positively with performance at the concrete
      operational stage; there were no gender differences in PS performance at both
      stages, and both the grade and consecutive year of taking the computer course had
      an effect on PS ability performance at both stages. Those in the lowest grade and
      those taking the course for the first year reported lower performances than their
      older counterparts. These findings may help curriculum designers across the world
      develop efficient approaches to teaching computer courses.

PMID- 30208040
TI  - Mechanical and dynamic characterization of prosthetic feet for high activity
      users during weighted and unweighted walking.
AB  - Many Service members and Veterans with lower-limb amputations have the potential
      for high function and the desire to resume physically demanding occupations that
      require them to carry heavy loads (e.g., military service, firefighters, farmers,
      ranchers, construction workers). However, it is currently unclear which
      prosthetic feet best accommodate heavy load carriage while also providing good
      overall function and mobility during unweighted activities. The main objective of
      this study was to investigate the ability of currently available prosthetic ankle
      foot systems to accommodate weighted walking by examining the mechanical
      characteristics (i.e., forefoot stiffness) and dynamic function (i.e., rocker
      radius, effective foot length ratio, and late-stance energy return) of prosthetic
      feet designed for high activity users. Load versus deflection curves were
      obtained for nine prosthetic ankle-foot systems using a servohydraulic test frame
      and load cell. Effective roll-over shape characteristics and late-stance energy
      return measures were then obtained using quantitative gait analysis for three
      users with unilateral, transtibial amputation. Results from mechanical and
      dynamic testing showed that although forefoot stiffness varied across the nine
      feet investigated in this study, changes measured in roll-over shape radius and
      effective foot length ratio were relatively small in response to weighted
      walking. At the same time, prosthetic feet with more compliant forefoot keel
      structures appeared to provide more late-stance energy return compared to feet
      with stiffer forefoot keel structures. These results suggest that prosthetic
      ankle-foot systems with compliant forefoot keel structures may better accommodate
      weighted walking by reducing the metabolic cost of physically demanding
      activities. However, to more fully understand the biomechanical and functional
      implications of these results, other factors, such as the residual-limb strength
      of the user and the overall stiffness profile of the prosthetic foot, should also
      be considered.

PMID- 30208041
TI  - Use of reproducible research practices in public health: A survey of public
      health analysts.
AB  - OBJECTIVE: Use of reproducible research practices improves the quality of science
      and the speed of scientific development. We sought to understand use of
      reproducible research practices in public health and associated barriers and
      facilitators. METHODS: In late 2017, we surveyed members of the American Public
      Health Association Applied Public Health Statistics section and others; 247 of
      278 who screened eligible answered the survey, and 209 answered every applicable
      question. The survey included questions about file management, code annotation
      and documentation, reproducibility of analyses, and facilitators and barriers of
      using reproducible practices. RESULTS: Just 14.4% of participants had shared
      code, data, or both. Many participants reported their data (33%) and code (43.2%)
      would be difficult for colleagues to find if they left their institution. Top
      reported barriers to using reproducible practices were data privacy (49.8%) and
      lack of time (41.7%). Participants suggested training (50.9%) and requirements by
      journals (44.4%) and funders (40.2%) to increase use of reproducible research
      practices. CONCLUSIONS: Increasing use of reproducible research practices is
      important for public health and requires action from researchers, training
      programs, funders, and journals.

PMID- 30208043
TI  - Administration of mycophenolic acid is not associated with malformations in
      descendants from kidney transplanted males.
AB  - BACKGROUND: In pregnant women, the use of Mycophenolic acid (MPA) is associated
      with teratogenicity. Recently, the European Medicines Agency (EMEA) and the
      Spanish Agency of Medicine and Sanitary Products (AEMPS) warned about the
      potential teratogenic effects of MPA. These adverse events may occur even in
      children from males on treatment with MPA. However, evidence of malformations in
      offsprings of male kidney transplanted patients (KT) exposed to MPA is limited.
      Thus, the present study aimed to evaluate the incidence of offspring
      malformations in children of renal transplanted males under MPA. MATERIALS AND
      METHODS: We conducted a retrospective study in which we evaluated the incidence
      of malformations in descendants from male recipients that were exposed or not to
      MPA before and at the time of conception. Two groups of patients were evaluated.
      Those exposed to MPA (MPA group, n = 20) and the non-MPA group (n = 13) that
      included patients that did not receive AZA (n = 5) and eight that did receive AZA
      (n = 8) at the time of conception. RESULTS: A total of forty-nine post-transplant
      conceptions were identified from 33 different renal transplanted males. MPA was
      used as the immunosuppressant in 28 of the conceptions. Males from the non-MPA
      group fathered the other 21 children. Median time from grafting to conception was
      6.1 (IQR 2.4-11.1) years, and it was similar between groups. There were eight
      miscarriage episodes, 2 in the non-MPA group and 6 in the MPA group although
      differences were not reached. After that, all patients had children without
      problems. No malformations were detected in any of the 49 regardless whether they
      were exposed or not to MPA. CONCLUSIONS: No evidence of MPA-associated
      malformations was observed in descendants of kidney transplanted males on
      treatment with MPA. Further research is warranted to confirm our findings to
      properly advice transplanted males keen to procreate.

PMID- 30208042
TI  - Pedigree data indicate rapid inbreeding and loss of genetic diversity within
      populations of native, traditional dog breeds of conservation concern.
AB  - Increasing concern is directed towards genetic diversity of domestic animal
      populations because strong selective breeding can rapidly deplete genetic
      diversity of socio-economically valuable animals. International conservation
      policy identifies minimizing genetic erosion of domesticated animals as a key
      biodiversity target. We used breeding records to assess potential indications of
      inbreeding and loss of founder allelic diversity in 12 native Swedish dog breeds,
      traditional to the country, ten of which have been identified by authorities as
      of conservation concern. The pedigrees dated back to the mid-1900, comprising 5
      11 generations and 350-66,500 individuals per pedigree. We assessed rates of
      inbreeding and potential indications of loss of genetic variation by measuring
      inbreeding coefficients and remaining number of founder alleles at five points in
      time during 1980-2012. We found average inbreeding coefficients among breeds to
      double-from an average of 0.03 in 1980 to 0.07 in 2012 -in spite of the majority
      of breeds being numerically large with pedigrees comprising thousands of
      individuals indicating that such rapid increase of inbreeding should have been
      possible to avoid. We also found indications of extensive loss of intra-breed
      variation; on average 70 percent of founder alleles are lost during 1980-2012.
      Explicit conservation goals for these breeds were not reflected in pedigree based
      conservation genetic measures; breeding needs to focus more on retaining genetic
      variation, and supplementary genomic analyses of these breeds are highly
      warranted in order to find out the extent to which the trends indicated here are
      reflected over the genomes of these breeds.

PMID- 30208044
TI  - Improving wellbeing and reducing future world population.
AB  - Almost 80% of the 4 billion projected increase in world population by 2100 comes
      from 37 Mid-African Countries (MACs), caused mostly by slow declines in Total
      Fertility Rate (TFR). Historically, TFR has declined in response to increases in
      wellbeing associated with economic development. We show that, when Infant
      Survival Rate (ISR, a proxy for wellbeing) has increased, MAC fertility has
      declined at the same rate, in relation to ISR, as it did in 61 comparable Other
      Developing Countries (ODCs) whose average fertility is close to replacement
      level. If MAC ISR were to increase at the historic rate of these ODCs, and TFR
      declined correspondingly, then the projected world population in 2100 would be
      decreasing and 1.1 billion lower than currently projected. Such rates of ISR
      increase, and TFR decrease, are quite feasible and have occurred in comparable
      ODCs. Increased efforts to improve the wellbeing of poor MAC populations are key.

PMID- 30208045
TI  - Welfare-Adjusted Life Years (WALY): A novel metric of animal welfare that
      combines the impacts of impaired welfare and abbreviated lifespan.
AB  - Currently, separate measures are used to estimate the impact of animal diseases
      on mortality and animal welfare. This article introduces a novel metric, the
      Welfare-Adjusted Life Year (WALY), to estimate disease impact by combining
      welfare compromise and premature death components. Adapting the Disability
      Adjusted Life Year approach used in human health audits, we propose WALY as the
      sum of a) the years lived with impaired welfare due to a particular cause and b)
      the years of life lost due to the premature death from the same cause. The years
      lived with impaired welfare are the product of the average duration of each
      welfare impediment, reflecting the actual condition that compromises animal
      welfare, the probability of an incident case developing and impaired welfare
      weights, representing the degree of impaired welfare. The years of life lost are
      calculated using the standard expected lifespan at the time of premature death.
      To demonstrate the concept, we estimated WALYs for 10 common canine diseases,
      namely mitral valve disease, dilated cardiomyopathy, chronic kidney disease,
      diabetes mellitus, atopic dermatitis, splenic haemangiosarcoma, appendicular
      osteosarcoma, cranial cruciate ligament disease, thoracolumbar intervertebral
      disc disease and cervical spondylomyelopathy. A survey of veterinarians (n = 61)
      was conducted to elicit impaired welfare weights for 35 welfare impediments.
      Paired comparison was the primary method to elicit weights, whereas visual
      analogue scale and time trade-off approaches rescaled these weights onto the
      desired scale, from 0 (the optimal welfare imaginable) to 1 (the worst welfare
      imaginable). WALYs for the 10 diseases were then estimated using the impaired
      welfare weights and published epidemiological data on disease impacts. Welfare
      impediment "amputation: one limb" and "respiratory distress" had the lowest and
      highest impaired welfare weights at 0.134 and 0.796, rescaled with a visual
      analogue scale, and 0.117 and 0.857, rescaled with time trade-off. Among the 10
      diseases, thoracolumbar intervertebral disc disease and atopic dermatitis had the
      smallest and greatest adverse impact on dogs with WALYs at 2.83 (95% UI: 1.54
      3.94) and 9.73 (95% uncertainty interval [UI]: 7.17-11.8), respectively. This
      study developed the WALY metric and demonstrated that it summarises welfare
      compromise as perceived by humans and total impact of diseases in individual
      animals. The WALY can potentially be used for prioritisation of disease
      eradication and control programs, quantification of population welfare and
      longitudinal surveillance of animal welfare in companion animals and may possibly
      be extended to production animals.

PMID- 30208046
TI  - Phenological responses of 215 moth species to interannual climate variation in
      the Pacific Northwest from 1895 through 2013.
AB  - Climate change has caused shifts in the phenology and distributions of many
      species but comparing responses across species is challenged by inconsistencies
      in the methodology and taxonomic and temporal scope of individual studies.
      Natural history collections offer a rich source of data for examining
      phenological shifts for a large number of species. We paired specimen records
      from Pacific Northwest insect collections to climate data to analyze the
      responses of 215 moth species to interannual climate variation over a period of
      119 years (1895-2013) during which average annual temperatures have increased in
      the region. We quantified the effects of late winter/early spring temperatures,
      averaged annually across the region, on dates of occurrence of adults, taking
      into account the effects of elevation, latitude, and longitude. We assessed
      whether species-specific phenological responses varied with adult flight season
      and larval diet breadth. Collection dates were significantly earlier in warmer
      years for 36.3% of moth species, and later for 3.7%. Species exhibited an average
      phenological advance of 1.9 days/ degrees C, but species-specific shifts ranged
      from an advance of 10.3 days/ degrees C to a delay of 10.6 days/ degrees C. More
      spring-flying species shifted their phenology than summer- or fall-flying
      species. These responses did not vary among groups defined by larval diet
      breadth. The highly variable phenological responses to climate change in Pacific
      Northwest moths agree with other studies on Lepidoptera and suggest that it will
      remain difficult to accurately forecast which species and ecological interactions
      are most likely to be affected by climate change. Our results also underscore the
      value of natural history collections as windows into long-term ecological trends.

PMID- 30208047
TI  - Different ommochrome pigment mixtures enable sexually dimorphic Batesian mimicry
      in disjunct populations of the common palmfly butterfly, Elymnias hypermnestra.
AB  - With varied, brightly patterned wings, butterflies have been the focus of much
      work on the evolution and development of phenotypic novelty. However, the
      chemical structures of wing pigments from few butterfly species have been
      identified. We characterized the orange wing pigments of female Elymnias
      hypermnestra butterflies (Lepidoptera: Nymphalidae: Satyrinae) from two Southeast
      Asian populations. This species is a sexually dimorphic Batesian mimic of several
      model species. Females are polymorphic: in some populations, females are dark,
      resemble conspecific males, and mimic Euploea spp. In other populations, females
      differ from males and mimic orange Danaus spp. Using LC-MS/MS, we identified nine
      ommochrome pigments: six from a population in Chiang Mai, Thailand, and five
      compounds from a population in Bali, Indonesia. Two ommochromes were found in
      both populations, and only two of the nine compounds have been previously
      reported. The sexually dimorphic Thai and Balinese populations are separated
      spatially by monomorphic populations in peninsular Malaysia, Singapore, and
      Sumatra, suggesting independent evolution of mimetic female wing pigments in
      these disjunct populations. These results indicate that other butterfly wing
      pigments remain to be discovered.

PMID- 30208049
TI  - Evidence-based pregnancy testing in clinical trials: Recommendations from a multi
      stakeholder development process.
AB  - Most clinical trials exclude pregnant women in order to avoid the possibility of
      adverse embryonic and/or fetal effects. Currently, there are no evidence-based
      guidelines regarding appropriate methods for identifying early pregnancy among
      research subjects. This lack of guidance results in wide variation in pregnancy
      testing plans, leading to the potential for inadequate protection against
      embryonic or fetal exposure in some cases and unnecessary burdens on research
      participants in others, as well as inefficiencies caused by disagreements among
      sponsors, investigators, and regulators. To address this issue, the Clinical
      Trials Transformation Initiative convened content experts and stakeholders to
      develop recommendations for pregnancy testing in clinical research based on
      currently available evidence. Recommendations included: 1) the study protocol
      should clearly state the rationale for pregnancy testing and the plan for
      handling positive and indeterminate tests; 2) protocols should include an
      assessment of the pregnancy testing plan advantages (reduced risk of embryo/fetal
      exposure) versus the burdens (participant burden, study team workload, costs); 3)
      protocols should assess the participant burdens regarding the likelihood of false
      negative and false positive results; 4) participant administered home pregnancy
      testing should be avoided in clinical trials; and 5) the consent process should
      describe the extent of knowledge about the study intervention's potential risk to
      the embryo/fetus and the limitations and consequences of pregnancy testing. CTTI
      has also developed an online tool to help implement these recommendations.

PMID- 30208048
TI  - Market share and recent hiring trends in anthropology faculty positions.
AB  - Between 1985 and 2014, the number of US doctoral graduates in Anthropology
      increased from about 350 to 530 graduates per year. This rise in doctorates
      entering the work force along with an overall decrease in the numbers of tenure
      track academic positions has resulted in highly competitive academic job market.
      We estimate that approximately79% of US anthropology doctorates do not obtain
      tenure-track positions at BA/BS, MA/MS, and PhD institutions in the US. Here, we
      examine where US anthropology faculty obtained their degrees and where they
      ultimately end up teaching as tenure-track faculty. Using data derived from the
      2014-2015 AnthroGuide and anthropology departmental web pages, we identify and
      rank PhD programs in terms of numbers of graduates who have obtained tenure-track
      academic jobs; examine long-term and ongoing trends in the programs producing
      doctorates for the discipline as a whole, as well as for the subfields of
      archaeology, bioanthropology, and sociocultural anthropology; and discuss gender
      inequity in academic anthropology within the US.

PMID- 30208050
TI  - Rapid bioerosion in a tropical upwelling coral reef.
AB  - Coral reefs persist in an accretion-erosion balance, which is critical for
      understanding the natural variability of sediment production, reef accretion, and
      their effects on the carbonate budget. Bioerosion (i.e. biodegradation of
      substrate) and encrustation (i.e. calcified overgrowth on substrate) influence
      the carbonate budget and the ecological functions of coral reefs, by substrate
      formation/consolidation/erosion, food availability and nutrient cycling. This
      study investigates settlement succession and carbonate budget change by
      bioeroding and encrusting calcifying organisms on experimentally deployed coral
      substrates (skeletal fragments of Stylophora pistillata branches). The substrates
      were deployed in a marginal coral reef located in the Gulf of Papagayo (Costa
      Rica, Eastern Tropical Pacific) for four months during the northern winter
      upwelling period (December 2013 to March 2014), and consecutively sampled after
      each month. Due to the upwelling environmental conditions within the Eastern
      Tropical Pacific, this region serves as a natural laboratory to study ecological
      processes such as bioerosion, which may reflect climate change scenarios. Time
      series analyses showed a rapid settlement of bioeroders, particularly of
      lithophagine bivalves of the genus Lithophaga/Leiosolenus (Dillwyn, 1817), within
      the first two months of exposure. The observed enhanced calcium carbonate loss of
      coral substrate (>30%) may influence seawater carbon chemistry. This is evident
      by measurements of an elevated seawater pH (>8.2) and aragonite saturation state
      (Omegaarag >3) at Matapalo Reef during the upwelling period, when compared to a
      previous upwelling event observed at a nearby site in distance to a coral reef
      (Marina Papagayo). Due to the resulting local carbonate buffer effect of the
      seawater, an influx of atmospheric CO2 into reef waters was observed. Substrates
      showed no secondary cements in thin-section analyses, despite constant seawater
      carbonate oversaturation (Omegaarag >2.8) during the field experiment. Micro
      Computerized Tomography (MUCT) scans and microcast-embeddings of the substrates
      revealed that the carbonate loss was primarily due to internal macrobioerosion
      and an increase in microbioerosion. This study emphasizes the interconnected
      effects of upwelling and carbonate bioerosion on the reef carbonate budget and
      the ecological turnovers of carbonate producers in tropical coral reefs under
      environmental change.

PMID- 30208052
TI  - The cultural origin of saving behavior.
AB  - Traditional economic interpretations have not been successful in explaining
      differences in saving rates across countries. One hypothesis is that savings
      respond to cultural specific social norms. The accepted view in economics so far
      is that culture does not have any effect on savings. We revisit this evidence
      using a novel dataset, which allows us to study the saving behavior of up to
      three generations of immigrants in the United Kingdom. Against the backdrop of
      existing evidence, we find that cultural preferences are an important explanation
      for cross-country differences in saving behavior, and their relevance persists up
      to three generations.

PMID- 30208051
TI  - Genetic analysis of a major international collection of cultivated apple
      varieties reveals previously unknown historic heteroploid and inbred
      relationships.
AB  - Domesticated apple (Malus x domestica Borkh.) is a major global crop and the
      genetic diversity held within the pool of cultivated varieties is important for
      the development of future cultivars. The aim of this study was to investigate the
      diversity held within the domesticated form, through the analysis of a major
      international germplasm collection of cultivated varieties, the UK National Fruit
      Collection, consisting of over 2,000 selections of named cultivars and seedling
      varieties. We utilised Diversity Array Technology (DArT) markers to assess the
      genetic diversity within the collection. Clustering attempts, using the software
      STRUCTURE revealed that the accessions formed a complex and historically admixed
      group for which clear clustering was challenging. Comparison of accessions using
      the Jaccard similarity coefficient allowed us to identify clonal and duplicate
      material as well as revealing pairs and groups that appeared more closely related
      than a standard parent-offspring or full-sibling relations. From further
      investigation, we were able to propose a number of new pedigrees, which revealed
      that some historically important cultivars were more closely related than
      previously documented and that some of them were partially inbred. We were also
      able to elucidate a number of parent-offspring relationships that had resulted in
      a number of important polyploid cultivars. This included reuniting polyploid
      cultivars that in some cases dated as far back as the 18th century, with diploid
      parents that potentially date back as far as the 13th century.

PMID- 30208053
TI  - Jaguar and puma captivity and trade among the Maya: Stable isotope data from
      Copan, Honduras.
AB  - From Moctezuma's zoo to animals kept in captivity at Teotihuacan, there is
      increasing evidence that Mesoamericans managed wild animals for a myriad of
      purposes. The present study situates ritualized animal management of highly
      symbolic fauna in the broader context of Classic Mesoamerica by examining another
      core site, the Maya center of Copan, Honduras (A.D. 426-822). In this study, we
      identify two animal populations among the faunal remains from public and private
      rituals spanning the Copan dynasty. One population, with diets heavily composed
      of atypically sourced C4 inputs indicative of artificial feeding, corresponds
      with the felids interred in Altar Q and Motmot caches. The second population is
      composed of felids and felid products bearing a predominance of C3 signatures
      indicative of a more natural dietary regime. As with Copan deer, species-specific
      delta18O variations within these felid populations further substantiates the
      postulation that an expansive faunal trade network operated throughout the
      greater Copan Valley and beyond. Animals routed from sites of capture into the
      mesh of this network would have been processed into pelts, venison and other
      secondary goods or delivered alive to centers of state power for ritual usage and
      display. Our data reveal that at Copan, wild animals were routinely brought into
      intimate contact with human settlements to be managed and physically manipulated
      in a variety of ways in order to fulfill ritual and symbolic purposes.

PMID- 30208055
TI  - Impacts of rainforest fragmentation on the composition of ground-active
      vertebrate communities and their patterns of seed consumption.
AB  - Post-dispersal seed consumption by rainforest vertebrates on the forest floor can
      substantially influence the community dynamics of rainforest trees. Studies of
      rainforest vertebrate seed predators at a community level, however, are lacking.
      Furthermore, there is very limited understanding of the effects of forest
      fragmentation on seed predators and their feeding behaviour. Here, we test
      whether communities of vertebrate seed predators, and their patterns of feeding
      on rainforest tree seeds, are altered when clearing creates forest fragments in
      an agricultural matrix. Using infra-red trail cameras deployed at stations with
      and without seeds of 20 local tree species, we identified four mammal and three
      bird species (from 18 recorded vertebrate taxa at mainly species level) as common
      post-dispersal seed predators in subtropical rainforest of eastern Australia.
      Statistical comparisons of species-specific frequencies between six sites in
      continuous forest and six in small rainforest fragments (4-21 ha) showed that
      habitat fragmentation substantially altered species composition of seed predator
      communities. Two species, both small rodents, had lower abundances in fragments
      than in continuous forest, while higher abundances were observed in fragments for
      a further four species: two small birds, a medium-sized marsupial and the small
      non-native rodent Rattus rattus. The abundance of one larger bird species did not
      change. Predatory interest in seeds was also significantly affected by habitat
      fragmentation and generally increased in each species' habitat of greater
      abundance. Collectively, seed predators showed behaviours associated with
      potential or actual seed consumption on an average of 43% of camera days with
      seeds, with about 50% of seeds physically removed or damaged after five days'
      exposure. Camera data have revealed community-level changes in seed predator
      abundance and feeding that are likely to cause altered patterns of plant
      recruitment following rainforest fragmentation, but these will be complex in
      nature.

PMID- 30208054
TI  - The Trim family of genes and the retina: Expression and functional
      characterization.
AB  - To better understand the mechanisms that govern the development of retinal
      neurons, it is critical to gain additional insight into the specific intrinsic
      factors that control cell fate decisions and neuronal maturation. In the
      developing mouse retina, Atoh7, a highly conserved transcription factor, is
      essential for retinal ganglion cell development. Moreover, Atoh7 expression in
      the developing retina occurs during a critical time period when progenitor cells
      are in the process of making cell fate decisions. We performed transcriptome
      profiling of Atoh7+ individual cells isolated from mouse retina. One of the genes
      that we found significantly correlated with Atoh7 in our transcriptomic data was
      the E3 ubiquitin ligase, Trim9. The correlation between Trim9 and Atoh7 coupled
      with the expression of Trim9 in the early mouse retina led us to hypothesize that
      this gene may play a role in the process of cell fate determination. To address
      the role of Trim9 in retinal development, we performed a functional analysis of
      Trim9 in the mouse and did not detect any morphological changes in the retina in
      the absence of Trim9. Thus, Trim9 alone does not appear to be involved in cell
      fate determination or early ganglion cell development in the mouse retina. We
      further hypothesize that the reason for this lack of phenotype may be
      compensation by one of the many additional TRIM family members we find expressed
      in the developing retina.

PMID- 30208057
TI  - Effect of seawater temperature, pH, and nutrients on the distribution and
      character of low abundance shallow water benthic foraminifera in the Galapagos.
AB  - In order to help predict the effects of anthropogenic stressors on shallow water
      carbonate environments, it is important to focus research on regions containing
      natural oceanographic gradients, particularly with respect to interactions
      between oceanography and ecologically sensitive carbonate producers. The
      Galapagos Archipelago, an island chain in the eastern equatorial Pacific, spans a
      natural nutrient, pH, and temperature gradient due to the interaction of several
      major ocean currents. Further, the region is heavily impacted by the El Nino
      Southern Oscillation (ENSO) and the Galapagos exhibited widespread coral
      bleaching and degradation following the strong ENSO events of 1982-1983 and 1997
      1998. These findings are coupled with reports of unusually low abundances of time
      averaged benthic foraminiferal assemblages throughout the region. Foraminifera,
      shelled single-celled protists, are sensitive to environmental change and rapidly
      respond to alterations to their surrounding environment, making them ideal
      indicator species for the study of reef water quality and health. Here,
      statistical models and analyses were used to compare modern shallow water benthic
      foraminiferal assemblages from 19 samples spanning the Galapagos Archipelago to
      predominant oceanographic parameters at each collection site. Fisher alpha
      diversity indices, Ternary diagrams, Canonical Correspondence Analysis,
      regression tree analysis and FORAM-Index (FI; a single metric index for
      evaluating water quality associated with reef development) implied a combined
      impact from ENSO and upwelling from Equatorial Undercurrent (EUC) waters to
      primarily impact foraminiferal abundances and drive assemblage patterns
      throughout the archipelago. For instance, repeated ENSO temperature anomalies
      might be responsible for low foraminiferal density, while chronically high
      nutrients and low aragonite saturation and low pH-induced by EUC upwelling and La
      Nina anomalies-likely inhibited post-ENSO recovery, and caused foraminiferal
      assemblages to exhibit a heterotrophic dominance in the southern archipelago.
      What resulted are low FI values in the southern collection sites, indicating
      environments not conducive to endosymbiont development and/or recovery.

PMID- 30208058
TI  - Determinants of caesarean section in Bangladesh: Cross-sectional analysis of
      Bangladesh Demographic and Health Survey 2014 Data.
AB  - BACKGROUND: Caesarean section (CS) has been on the rise worldwide and Bangladesh
      is no exception. In Bangladesh, the CS rate, which includes both institutional
      and community-based deliveries, has increased from about 3% in 2000 to about 24%
      in 2014. This study examines the association of reported complications around
      delivery and socio-demographic, healthcare and spatial characteristics of mothers
      with CS, using data from the latest Bangladesh Demographic and Health Survey
      (BDHS). METHODS: The study is based on data from the 2014 BDHS. BDHS is a
      nationally representative survey which is conducted periodically and 2014 is the
      latest of the BDHS conducted. Data collected from 4,627 mothers who gave birth in
      health care institutions in three years preceding the survey were used in this
      study. RESULTS: Average age of the mothers was 24.6 years, while their average
      years of schooling were 3.2. Factors like mother being older, obese, residing in
      urban areas, first birth, maternal perception of large newborn size, husband
      being a professional, had higher number of antenatal care (ANC) visits, seeking
      ANC from private providers, and delivering in a private facility were
      statistically associated with higher rates of CS. CONCLUSIONS: Bangladesh health
      system urgently needs policy guideline with monitoring of clinical indications of
      CS deliveries to avoid unnecessary CS. Strict adherence to this guideline, along
      with enhance knowledge on the unsafe nature of the unnecessary CS can achieve
      increased institutional normal delivery in future; otherwise, an emergency
      procedure may end up being a lucrative practice.

PMID- 30208056
TI  - Repurposing antimalarial aminoquinolines and related compounds for treatment of
      retinal neovascularization.
AB  - Neovascularization is the pathological driver of blinding eye diseases such as
      retinopathy of prematurity, proliferative diabetic retinopathy, and wet age
      related macular degeneration. The loss of vision resulting from these diseases
      significantly impacts the productivity and quality of life of patients, and
      represents a substantial burden on the health care system. Current standard of
      care includes biologics that target vascular endothelial growth factor (VEGF), a
      key mediator of neovascularization. While anti-VGEF therapies have been
      successful, up to 30% of patients are non-responsive. Therefore, there is a need
      for new therapeutic targets, and small molecule inhibitors of angiogenesis to
      complement existing treatments. Apelin and its receptor have recently been shown
      to play a key role in both developmental and pathological angiogenesis in the
      eye. Through a cell-based high-throughput screen, we identified 4-aminoquinoline
      antimalarial drugs as potent selective antagonists of APJ. The prototypical 4
      aminoquinoline, amodiaquine was found to be a selective, non-competitive APJ
      antagonist that inhibited apelin signaling in a concentration-dependent manner.
      Additionally, amodiaquine suppressed both apelin-and VGEF-induced endothelial
      tube formation. Intravitreal amodaiquine significantly reduced choroidal
      neovascularization (CNV) lesion volume in the laser-induced CNV mouse model, and
      showed no signs of ocular toxicity at the highest doses tested. This work firmly
      establishes APJ as a novel, chemically tractable therapeutic target for the
      treatment of ocular neovascularization, and that amodiaquine is a potential
      candidate for repurposing and further toxicological, and pharmacokinetic
      evaluation in the clinic.

PMID- 30208059
TI  - Correlation between posterior tibial slope and sagittal alignment under weight
      bearing conditions in osteoarthritic knees.
AB  - INTRODUCTION: Posterior tibial slope (PTS) and sagittal alignment are important
      factors in the etiology of knee osteoarthritis and knee surgery. Clinically,
      sagittal alignment, which indicates flexion contracture of the knee, contributes
      to knee function in weight-bearing (WB) conditions. PTS and sagittal alignment
      under WB conditions in varus osteoarthritic knees are presumed to affect each
      other, but their association remains unclear. In this study, we aimed to clarify
      the association. MATERIAL AND METHODS: In total, 140 osteoarthritic varus knees
      were investigated. Under WB conditions, a three-dimensional (3D) alignment
      assessment system was applied via biplanar long-leg X-rays, using 3D-to-2D image
      registration technique. The evaluation parameters were as follows: 1) 3D
      mechanical flexion angle (3DMFA) in regards to sagittal alignment, 2) passing
      point in the WB line (PP), and 3) medial and lateral PTS. RESULTS: The medial and
      lateral PTS showed a positive correlation with 3DMFA and PP, respectively (medial
      PTS-3DMFA, p = 0.001; medial PTS-PP, p < 0.0001; lateral PTS-3DMFA, p < 0.0001;
      lateral PTS-PP, p = 0.002). The flexion contracture group with 3DMFA >5 degrees 
      demonstrated greater PTS than non-flexion contracture group (medial PTS, p =
      0.006; lateral PTS, p = 0.006). CONCLUSIONS: Both medial and lateral PTS were
      correlated with sagittal alignment under WB conditions and were larger in the
      flexion contracture group. This finding can explain the function to take the load
      articular surface parallel to the ground for holding the balance in WB conditions
      in the sagittal plane for osteoarthritic knees. Moreover, surgeons may be
      required to decrease the PTS during knee arthroplasty to restore full extension
      in knees of patients with fixed flexion contracture.

PMID- 30208060
TI  - Simple changes of individual studies can improve the reproducibility of the
      biomedical scientific process as a whole.
AB  - We developed a new probabilistic model to assess the impact of recommendations
      rectifying the reproducibility crisis (by publishing both positive and 'negative'
      results and increasing statistical power) on competing objectives, such as
      discovering causal relationships, avoiding publishing false positive results, and
      reducing resource consumption. In contrast to recent publications our model
      quantifies the impact of each single suggestion not only for an individual study
      but especially their relation and consequences for the overall scientific
      process. We can prove that higher-powered experiments can save resources in the
      overall research process without generating excess false positives. The better
      the quality of the pre-study information and its exploitation, the more likely
      this beneficial effect is to occur. Additionally, we quantify the adverse effects
      of both neglecting good practices in the design and conduct of hypotheses-based
      research, and the omission of the publication of 'negative' findings. Our
      contribution is a plea for adherence to or reinforcement of the good scientific
      practice and publication of 'negative' findings.

PMID- 30208061
TI  - Robust activation of microhomology-mediated end joining for precision gene
      editing applications.
AB  - One key problem in precision genome editing is the unpredictable plurality of
      sequence outcomes at the site of targeted DNA double stranded breaks (DSBs). This
      is due to the typical activation of the versatile Non-homologous End Joining
      (NHEJ) pathway. Such unpredictability limits the utility of somatic gene editing
      for applications including gene therapy and functional genomics. For germline
      editing work, the accurate reproduction of the identical alleles using NHEJ is a
      labor intensive process. In this study, we propose Microhomology-mediated End
      Joining (MMEJ) as a viable solution for improving somatic sequence homogeneity in
      vivo, capable of generating a single predictable allele at high rates (56% ~ 86%
      of the entire mutant allele pool). Using a combined dataset from zebrafish (Danio
      rerio) in vivo and human HeLa cell in vitro, we identified specific contextual
      sequence determinants surrounding genomic DSBs for robust MMEJ pathway
      activation. We then applied our observation to prospectively design MMEJ-inducing
      sgRNAs against a variety of proof-of-principle genes and demonstrated high levels
      of mutant allele homogeneity. MMEJ-based DNA repair at these target loci
      successfully generated F0 mutant zebrafish embryos and larvae that faithfully
      recapitulated previously reported, recessive, loss-of-function phenotypes. We
      also tested the generalizability of our approach in cultured human cells.
      Finally, we provide a novel algorithm, MENTHU (http://genesculpt.org/menthu/),
      for improved and facile prediction of candidate MMEJ loci. We believe that this
      MMEJ-centric approach will have a broader impact on genome engineering and its
      applications. For example, whereas somatic mosaicism hinders efficient recreation
      of knockout mutant allele at base pair resolution via the standard NHEJ-based
      approach, we demonstrate that F0 founders transmitted the identical MMEJ allele
      of interest at high rates. Most importantly, the ability to directly dictate the
      reading frame of an endogenous target will have important implications for gene
      therapy applications in human genetic diseases.

PMID- 30208063
TI  - Linkages between straw decomposition rate and the change in microbial fractions
      and extracellular enzyme activities in soils under different long-term
      fertilization treatments.
AB  - In order to study the linkages between straw decomposition rate and the change in
      soil biological properties after straw addition to different fertilized soils, we
      collected soils from three long-term fertilization treatments (no-fertilizer, CK;
      nitrogen, phosphorus, and potassium fertilizers, NPK; NPK plus straw (S), NPKS),
      and incubated maize straw with these soils at 25 degrees C for 75 days. The
      average straw carbon dioxide (CO2) emission rate in the CK+straw (S), NPK+S, and
      NPKS+S treatments was 0.58+/-0.51, 0.66+/-0.53, and 0.74+/-0.58 MUg C g-1soil h
      1, respectively. The average increase in the contents of fungi, bacteria, and
      Actinomycetes under straw addition treatments than the control soils (CK, NPK,
      and NPKS, respectively) changed in the order of CK+S<=NPK+S <NPKS+S, while
      bacteria and Actinomycetes peaked later in the CK+SthanNPK+S and NPKS+S
      treatments. Bacterial abundance unchanged, Actinomycetes abundance decreased, but
      fungal abundance significantly increased in soils after straw addition. The
      average increase in the activities of beta-glucosidase (BG), beta-D
      cellobiosidase (CB), and beta-xylosidase (XYL) differed as: CK+S<NPK+S <= NPKS+S,
      and the highest activities and increments of them occurred later in the CK+S than
      NPK+S and NPKS+S treatments. Straw CO2 emission rate was poorly correlated with
      changes in the contents of microbial fractions across all straw addition
      treatments, but it was significant positively correlated with the increased
      activities of BG, CB, and XYL under the NPK+S and NPKS+S treatments. Our results
      indicated that chemical fertilization and straw return soils differently
      increased straw decomposition because of the different increases in microbial
      fractions and soil enzyme activities when compared to the no-fertilizer soil, and
      the decomposition process was more closely correlated with C-obtaining enzymes
      than microbial fractions.

PMID- 30208062
TI  - Contraceptive, condom and dual method use at last coitus among perinatally and
      horizontally HIV-infected young women in Atlanta, Georgia.
AB  - OBJECTIVE: To evaluate factors within the social-ecological framework associated
      with most or moderately effective contraception, condom and dual method use at
      last coitus among young, HIV-infected women in Atlanta. METHODS: This is a cross
      sectional study conducted from November, 2013 until August, 2015 at the Grady
      Infectious Disease Clinic in Atlanta, Georgia. We recruited perinatally and
      horizontally HIV-infected women of ages 14-30 years to complete an audio computer
      assisted self-interview. We evaluated factors within a social-ecological
      framework associated with most or moderately effective contraceptive use
      (hormonal contraception or an IUD), condom use, and dual method use (use of
      condom and most or moderately effective contraceptive) at last coitus. RESULTS:
      Of 103 women enrolled, 74 reported a history of sexual activity. The average age
      was 22.1; 89% were African American, 52% were perinatally infected, 89% received
      combination antiretroviral therapy, and 63% had undetectable viral loads. At last
      coitus, 46% reported most or moderately effective contraception, 62% reported
      condom use and 27% reporting dual-method use. The odds of most or moderately
      effective contraceptive use was significantly reduced among those with detectable
      viral loads (versus undetectable viral loads; aOR 0.13 [0.04, 0.38]). Older age
      (aOR 0.85 [0.74, 0.98] and more frequent coitus (>once/week versus < = once/week;
      aOR 0.24 [0.08, 0.72]) was significantly associated with reduced condom use.
      Having a detectable viral load (versus undetectable viral loads; aOR 0.13 [0.03,
      0.69]) and more frequent coitus (>once/week versus < = once/week; aOR 0.14
      [0.03,0.82]), was associated with reduced dual method use, while being enrolled
      in school (aOR 5.63 [1.53, 20.71]) was significantly associated with increased
      dual method use. CONCLUSIONS: Most or moderately effective contraception, condom
      and dual method use remained inadequate in this cohort of young HIV-infected
      women. Individual-level interventions are needed to increase the uptake of dual
      methods with user-independent contraceptives.

PMID- 30208064
TI  - Zebrafish snai2 mutants fail to phenocopy morphant phenotypes.
AB  - Snail2 is a zinc-finger transcription factor best known to repress expression of
      genes encoding cell adherence proteins to facilitate induction of the epithelial
      to-mesenchymal transition. While this role has been best documented in the
      developmental migration of the neural crest and mesoderm, here we expand on
      previously reported preliminary findings that morpholino knock-down of snai2
      impairs the generation of hematopoietic stem cells (HSCs) during zebrafish
      development. We demonstrate that snai2 morphants fail to initiate HSC
      specification and show defects in the somitic niche of migrating HSC precursors.
      These defects include a reduction in sclerotome markers as well as in the Notch
      ligands dlc and dld, which are known to be essential components of HSC
      specification. Accordingly, enforced expression of the Notch1-intracellular
      domain was capable of rescuing HSC specification in snai2 morphants. To parallel
      our approach, we obtained two mutant alleles of snai2. In contrast to the
      morphants, homozygous mutant embryos displayed no defects in HSC specification or
      in sclerotome development, and mutant fish survive into adulthood. However, when
      these homozygous mutants were injected with snai2 morpholino, HSCs were
      improperly specified. In summary, our morpholino data support a role for Snai2 in
      HSC development, whereas our mutant data suggest that Snai2 is dispensable for
      this process. Together, these findings further support the need for careful
      consideration of both morpholino and mutant phenotypes in studies of gene
      function.

PMID- 30208065
TI  - Differential changes in the onset of spring across US National Wildlife Refuges
      and North American migratory bird flyways.
AB  - Warming temperatures associated with climate change can have indirect effects on
      migratory birds that rely on seasonally available food resources and habitats
      that vary across spatial and temporal scales. We used two heat-based indices of
      spring onset, the First Leaf Index (FLI) and the First Bloom Index (FBI), as
      proxies of habitat change for the period 1901 to 2012 at three spatial scales:
      the US National Wildlife Refuge System; the four major bird migratory flyways in
      North America; and the seasonal ranges (i.e., breeding and non-breeding grounds)
      of two migratory bird species, Blue-winged Warbler (Vermivora cyanoptera) and
      Whooping Crane (Grus americana). Our results show that relative to the historical
      range of variability, the onset of spring is now earlier in 76% of all wildlife
      refuges and extremely early (i.e., exceeding 95% of historical conditions) in 49%
      of refuges. In all flyways but the Pacific, the rate of spring advance is
      generally greater at higher latitudes than at lower latitudes. This differential
      rate of advance in spring onset is most pronounced in the Atlantic flyway,
      presumably because of a "warming hole" in the southeastern US. Both FLI and FBI
      have advanced markedly in the breeding ranges-but not the non-breeding ranges-of
      the two selected bird species, albeit with considerable intra-range variation.
      Differences among species in terms of migratory patterns and the location and
      extent of seasonal habitats, as well as shifts in habitat conditions over time,
      may complicate predictions of the vulnerability of migratory birds to climate
      change effects. This study provides insight into how differential shifts in the
      phenology of disparate but linked habitats could inform local- to landscape-scale
      management strategies for the conservation of migratory bird populations.

PMID- 30208066
TI  - Relationships between physical qualities and key performance indicators during
      match-play in senior international rugby union players.
AB  - The use of physical tests to profile physical capabilities, and provide training
      direction to athletes is common practice. Likewise, in professional team sports,
      notational analysis codes the key contributions of each player during
      competition. Limited studies have however investigated relationships between
      physical capabilities and key performance indicators (KPIs) of rugby union match
      play. Elite professional players, categorised as forwards (n = 15) or backs (n =
      14), from an international rugby union squad (n = 29) undertook assessments of
      isometric mid-thigh pull (IMTP), bilateral and unilateral countermovement jumps
      (CMJ) and drop jumps (DJ; from 40 and 20 cm, respectively), and assessment of
      acceleration (10 m), a 5 m weighted sled drive, and a Yo-Yo intermittent recovery
      test level 1 (Yo-Yo IRTL1). Game statistics of the same players from 92 matches
      (~23 matches per player) during the 2014-15 season were analysed for effort and
      performance-based metrics. For forwards, Yo-Yo IRTL1 correlated significantly
      with; number of tackles made (r = 0.717), first three players at a ruck in both
      attack (r = 0.568) and defence (r = 0.581), number of effective rucks (r =
      0.630), total possessions (r = 0.522), passes made (r = 0.651), percentage of
      carries over the gainline (r = 0.610), effective ruck success (r = 0.600), tackle
      success (r = 0.540), and the number of turnovers made (r = 0.518). Drop jump
      performance in forwards was associated with; the number of clean breaks (r =
      0.558), dominant collisions (r = 0.589), and offloads (r = 0.594). For backs, the
      sled-drive test correlated with; number of carries (r = -0.751), first three
      players at an attacking ruck (r = -0.613), effective attacking rucks (r = 
      0.584), number of dominant collisions (r = -0.792) and offloads (r = -0.814).
      Likewise, for backs, IMTP peak force was related to; the number of possessions (r
      = 0.793), passes made (r = 0.792), effective attacking ruck percentage (r =
      0.628), and the number of offloads (r = 0.621) whilst relative peak force
      correlated with; the percentage of carries over the gainline (r = 0.533), percent
      tackle success (r = 0.603) and effective attacking ruck percentage (r = 0.584).
      Regression analyses highlighted that only a small number of variables (i.e.,
      carries, tackles, attacking and defensive first three at ruck) returned
      practically achievable changes (<20%) in physical qualities. In spite of this,
      and while leaving scope identification of further physical and/or performance
      predictors, greater strength, power and intermittent running performance were
      positively related to match-derived KPIs during competition. This may provide a
      basis for better integrating the strategies used by physical and technical
      performance-focused coaching staff to improve key performance indicators, and
      thus match performance, of rugby union players.

PMID- 30208067
TI  - Effect of climate change on distribution of species of common horned frogs in
      South America.
AB  - Our main objectives were to verify the effect of climate change on distribution
      of frogs of the family Ceratophryidae and if the legal protection areas in South
      America will be effective or ineffective in ensuring the preservation of the
      toads this family in coming decades. The results showed that in the last 140,000
      years, species of the family Ceratophryidae expanded and contracted their
      distribution areas, which naturally reflected the climate and vegetation changes
      in the Quaternary of South America. The maps of projections showed that changes
      in temperature determined the area of habitat suitability of 63.7% of the species
      of ceratophrids both during the last interglacial period and nowadays, and it
      seems that this will also be the case for the next 62 years. Given the current
      concerns about future extinctions in the tropics, it is prudent to examine, with
      special attention, the effects of climate fluctuations on the diversity and
      distribution of species, because the current estimates of reduction in
      biodiversity caused by habitat destruction and emission of greenhouse gases are
      comparable to estimated reductions during glacial intervals.

PMID- 30208068
TI  - Increased H. pylori stool shedding and EPIYA-D cagA alleles are associated with
      gastric cancer in an East Asian hospital.
AB  - BACKGROUND: Helicobacter pylori infection increases risk for gastric cancer.
      Geographic variation in gastric cancer risk has been attributed to variation in
      carriage and type of the H. pylori oncogene cagA. Colonization density may also
      influence disease and cagA has been associated with higher shedding in stool.
      However, the relationship between H. pylori load in the stool and in the stomach
      is not clear. METHODS: To investigate possible differences in H. pylori load in
      the stomach and shedding in stool, H. pylori load and cagA genotype were assessed
      using droplet digital PCR assays on gastric mucosa and stool samples from 49 urea
      breath test-positive individuals, including 25 gastric cancer and 24 non-cancer
      subjects at Henan Cancer Hospital, Henan, China. RESULTS: Quantitation of H.
      pylori DNA indicated similar gastric loads among cancer and non-cancer cases, but
      the gastric cancer group had a median H. pylori load in the stool that was six
      times higher than that of the non-cancer subjects. While the cagA gene was
      uniformly present among study subjects, only 70% had the East Asian cagA allele,
      which was significantly associated with gastric cancer (Fisher's Exact Test, p =
      0.03). CONCLUSION: H. pylori persists in a subset of gastric cancer cases and
      thus may contribute to cancer progression. In this East Asian population with a
      high prevalence of the cagA gene, the East Asian allele could still provide a
      marker for gastric cancer risk. IMPACT: This study contributes to our
      understanding of H. pylori dynamics in the context of pathological changes.

PMID- 30208069
TI  - Metabarcoding by capture using a single COI probe (MCSP) to identify and quantify
      fish species in ichthyoplankton swarms.
AB  - The ability to determine the composition and relative frequencies of fish species
      in large ichthyoplankton swarms could have extremely important ecological
      applications However, this task is currently hampered by methodological
      limitations. We proposed a new method for Amazonian species based on
      hybridization capture of the COI gene DNA from a distant species (Danio rerio),
      absent from our study area (the Amazon basin). The COI sequence of this species
      is approximately equidistant from all COI of Amazonian species available. By
      using this sequence as probe we successfully facilitated the simultaneous
      identification of fish larvae belonging to the order Siluriformes and to the
      Characiformes represented in our ichthyoplankton samples. Species relative
      frequencies, estimated by the number of reads, showed almost perfect correlations
      with true frequencies estimated by a Sanger approach, allowing the development of
      a quantitative approach. We also proposed a further improvement to a previous
      protocol, which enables lowering the sequencing effort by 40 times. This new
      Metabarcoding by Capture using a Single Probe (MCSP) methodology could have
      important implications for ecology, fisheries management and conservation in fish
      biodiversity hotspots worldwide. Our approach could easily be extended to other
      plant and animal taxa.

PMID- 30208070
TI  - The Nordic Maintenance Care program: Effectiveness of chiropractic maintenance
      care versus symptom-guided treatment for recurrent and persistent low back pain-A
      pragmatic randomized controlled trial.
AB  - BACKGROUND: For individuals with recurrent or persistent non-specific low back
      pain (LBP), exercise and exercise combined with education have been shown to be
      effective in preventing new episodes or in reducing the impact of the condition.
      Chiropractors have traditionally used Maintenance Care (MC), as secondary and
      tertiary prevention strategies. The aim of this trial was to investigate the
      effectiveness of MC on pain trajectories for patients with recurrent or
      persistent LBP. METHOD: This pragmatic, investigator-blinded, two arm randomized
      controlled trial included consecutive patients (18-65 years old) with non
      specific LBP, who had an early favorable response to chiropractic care. After an
      initial course of treatment, eligible subjects were randomized to either MC or
      control (symptom-guided treatment). The primary outcome was total number of days
      with bothersome LBP during 52 weeks collected weekly with text-messages (SMS) and
      estimated by a GEE model. RESULTS: Three hundred and twenty-eight subjects were
      randomly allocated to one of the two treatment groups. MC resulted in a reduction
      in the total number of days per week with bothersome LBP compared with symptom
      guided treatment. During the 12 month study period, the MC group (n = 163, 3
      dropouts) reported 12.8 (95% CI = 10.1, 15.5; p = <0.001) fewer days in total
      with bothersome LBP compared to the control group (n = 158, 4 dropouts) and
      received 1.7 (95% CI = 1.8, 2.1; p = <0.001) more treatments. Numbers presented
      are means. No serious adverse events were recorded. CONCLUSION: MC was more
      effective than symptom-guided treatment in reducing the total number of days over
      52 weeks with bothersome non-specific LBP but it resulted in a higher number of
      treatments. For selected patients with recurrent or persistent non-specific LBP
      who respond well to an initial course of chiropractic care, MC should be
      considered an option for tertiary prevention.

PMID- 30208072
TI  - Characterization of a novel member of the family Caulimoviridae infecting
      Dioscorea nummularia in the Pacific, which may represent a new genus of dsDNA
      plant viruses.
AB  - We have characterized the complete genome of a novel circular double-stranded DNA
      virus, tentatively named Dioscorea nummularia-associated virus (DNUaV), infecting
      Dioscorea nummularia originating from Samoa. The genome of DNUaV comprised 8139
      bp and contained four putative open reading frames (ORFs). ORFs 1 and 2 had no
      identifiable conserved domains, while ORF 3 had conserved motifs typical of
      viruses within the family Caulimoviridae including coat protein, movement
      protein, aspartic protease, reverse transcriptase and ribonuclease H. A
      transactivator domain, similar to that present in members of several
      caulimoviridae genera, was also identified in the putative ORF 4. The genome
      size, organization, and presence of conserved amino acid domains are similar to
      other viruses in the family Caulimoviridae. However, based on nucleotide sequence
      similarity and phylogenetic analysis, DNUaV appears to be a distinct novel member
      of the family and may represent a new genus.

PMID- 30208071
TI  - Spray-dried plasma attenuates inflammation and lethargic behaviors of pregnant
      mice caused by lipopolysaccharide.
AB  - This study evaluated whether dietary spray-dried plasma (SDP) can ameliorate
      inflammation, lethargic behaviors, and impairment of reproduction caused by
      lipopolysaccharide (LPS) challenge during late pregnancy. Two experiments were
      conducted with 125 mated female mice (C57BL/6 strain) in each experiment. All
      mice were shipped from a vendor on the gestation day (GD) 1 and arrived at the
      laboratory on GD 3. Mice were randomly assigned to dietary treatments with or
      without 8% SDP in the diet. On GD 17, mice determined pregnant by BW and abdomen
      shape were randomly assigned to intraperitoneal injections with or without 2 MUg
      LPS. In experiment 1, 17 mice (26.7 +/- 1.7 g BW) were identified pregnant and
      euthanized 6 h after the LPS challenge to measure inflammatory responses in
      uterus and placenta. In experiment 2, 44 mice (26.0 +/- 1.6 g BW) were identified
      pregnant and euthanized 24 h after the LPS challenge to assess behavior and late
      term pregnancy loss. Growth performance and reproductive responses, such as loss
      of pregnancy, percentage of fetal death, and etc., were measured in all pregnant
      mice. The LPS challenge increased (P < 0.05) uterine and placental tumor necrosis
      factor-alpha and interferon-gamma, late-term pregnancy loss, and lethargy score,
      and decreased (P < 0.05) uterine transforming growth factor-beta1, moving time
      and number of rearing, and growth and feed intake. The SDP decreased (P < 0.05)
      concentrations of both pro-inflammatory and anti-inflammatory cytokines in one or
      both tissues, and the lethargy score, and increased (P < 0.05) moving time and
      number of rearing, growth of pregnant mice, and fetal weight. However, the SDP
      did not affect late-term pregnancy loss caused by the LPS challenge.
      Consequently, dietary SDP attenuated acute inflammation and lethargic behaviors
      of pregnant mice caused by the LPS challenge, but did not affect late-term
      pregnancy loss after the acute inflammation.

PMID- 30208074
TI  - Microalgal cultivation for biofertilization in rice plants using a vertical semi
      closed airlift photobioreactor.
AB  - Nitrogen (N) is one of the most important limiting factors in conventional rice
      (Oryza sativa) production, which heavily relies on synthetic fertilizers. In this
      study, we researched on the development and use of a vertical semi-closed airlift
      photobioreactor (PBR) for microalgal cultivation and subsequently determined the
      efficacy of microalgae-based fertilizers to rice plant growth. The PBR system was
      developed to produce two strains of N2-fixing cyanobacteria (Anabaena sp. UTEX
      2576, Nostoc muscorum UTEX 2209S), and a polyculture of Chlorella vulgaris (UTEX
      2714) and Scenedesmus dimorphus (UTEX 1237). When these biofertilizers were
      evaluated for rice under the greenhouse conditions, results showed that the rice
      plant heights treated with polyculture-based microalgal biomass were similar to
      or better than the urea treatment. The effects of the inoculation of the N2
      fixing cyanobacterial inoculation on seedling growth was not statistically
      significant. In conclusion, the vertical semi-closed system PBR cultivation
      method developed in this study proved to be a simple and effective method for
      cultivating microalgae. Demonstration of the reliable production system for N2
      fixing cyanobacteria and chlorophytes at a medium scale could potentially open
      the future application of microalgal biofertilizers in rice production.

PMID- 30208073
TI  - The relationship between greenspace and the mental wellbeing of adults: A
      systematic review.
AB  - INTRODUCTION: The view that interacting with nature enhances mental wellbeing is
      commonplace, despite a dearth of evidence or even agreed definitions of 'nature'.
      The aim of this review was to systematically appraise the evidence for
      associations between greenspace and mental wellbeing, stratified by the different
      ways in which greenspace has been conceptualised in quantitative research.
      METHODS: We undertook a comprehensive database search and thorough screening of
      articles which included a measure of greenspace and validated mental wellbeing
      tool, to capture aspects of hedonic and/or eudaimonic wellbeing. Quality and risk
      of bias in research were assessed to create grades of evidence. We undertook
      detailed narrative synthesis of the 50 studies which met the review inclusion
      criteria, as methodological heterogeneity precluded meta-analysis. RESULTS:
      Results of a quality assessment and narrative synthesis suggest associations
      between different greenspace characteristics and mental wellbeing. We identified
      six ways in which greenspace was conceptualised and measured: (i) amount of local
      area greenspace; (ii) greenspace type; (iii) visits to greenspace; (iv) views of
      greenspace; (v) greenspace accessibility; and (vi) self-reported connection to
      nature. There was adequate evidence for associations between the amount of local
      area greenspace and life satisfaction (hedonic wellbeing), but not personal
      flourishing (eudaimonic wellbeing). Evidence for associations between mental
      wellbeing and visits to greenspace, accessibility, and types of greenspace was
      limited. There was inadequate evidence for associations with views of greenspace
      and connectedness to nature. Several studies reported variation in associations
      between greenspace and wellbeing by life course stage, gender, levels of
      physically activity or attitudes to nature. CONCLUSIONS: Greenspace has positive
      associations with mental wellbeing (particularly hedonic wellbeing), but the
      evidence is not currently sufficient or specific enough to guide planning
      decisions. Further studies are needed, based on dynamic measures of greenspace,
      reflecting access and uses of greenspace, and measures of both eudaimonic and
      hedonic mental wellbeing.

PMID- 30208075
TI  - Malaria intensity in Colombia by regions and populations.
AB  - Determining the distribution of disease prevalence among heterogeneous
      populations at the national scale is fundamental for epidemiology and public
      health. Here, we use a combination of methods (spatial scan statistic,
      topological data analysis and epidemic profile) to study measurable differences
      in malaria intensity by regions and populations of Colombia. This study explores
      three main questions: What are the regions of Colombia where malaria is epidemic?
      What are the regions and populations in Colombia where malaria is endemic? What
      associations exist between epidemic outbreaks between regions in Colombia?
      Plasmodium falciparum is most prevalent in the Pacific Coast, some regions of the
      Amazon Basin, and some regions of the Magdalena Basin. Plasmodium vivax is the
      most prevalent parasite in Colombia, particularly in the Northern Amazon Basin,
      the Caribbean, and municipalities of Sucre, Antioquia and Cordoba. We find an
      acute peak of malarial infection at 25 years of age. Indigenous and Afrocolombian
      populations experience endemic malaria (with household transmission). We find
      that Plasmodium vivax decreased in the most important hotspots, often with
      moderate urbanization rate, and was re-introduced to locations with moderate but
      sustained deforestation. Infection by Plasmodium falciparum, on the other hand,
      steadily increased in incidence in locations where it was introduced in the 2009
      2010 generalized epidemic. Our findings suggest that Colombia is entering an
      unstable transmission state, where rapid decreases in one location of the country
      are interconnected with rapid increases in other parts of the country.

PMID- 30208076
TI  - Computational prediction of changes in brain metabolic fluxes during Parkinson's
      disease from mRNA expression.
AB  - BACKGROUND: Parkinson's disease is a widespread neurodegenerative disorder which
      affects brain metabolism. Although changes in gene expression during disease are
      often measured, it is difficult to predict metabolic fluxes from gene expression
      data. Here we explore the hypothesis that changes in gene expression for enzymes
      tend to parallel flux changes in biochemical reaction pathways in the brain
      metabolic network. This hypothesis is the basis of a computational method to
      predict metabolic flux changes from post-mortem gene expression measurements in
      Parkinson's disease (PD) brain. RESULTS: We use a network model of central
      metabolism and optimize the correspondence between relative changes in fluxes and
      in gene expression. To this end we apply the Least-squares with Equalities and
      Inequalities algorithm integrated with Flux Balance Analysis (Lsei-FBA). We
      predict for PD (1) decreases in glycolytic rate and oxygen consumption and an
      increase in lactate production in brain cortex that correspond with measurements
      (2) relative flux decreases in ATP synthesis, in the malate-aspartate shuttle and
      midway in the TCA cycle that are substantially larger than relative changes in
      glucose uptake in the substantia nigra, dopaminergic neurons and most other brain
      regions (3) shifts in redox shuttles between cytosol and mitochondria (4) in
      contrast to Alzheimer's disease: little activation of the gamma-aminobutyric acid
      shunt pathway in compensation for decreased alpha-ketoglutarate dehydrogenase
      activity (5) in the globus pallidus internus, metabolic fluxes are increased,
      reflecting increased functional activity. CONCLUSION: Our method predicts
      metabolic changes from gene expression data that correspond in direction and
      order of magnitude with presently available experimental observations during
      Parkinson's disease, indicating that the hypothesis may be useful for some
      biochemical pathways. Lsei-FBA generates predictions of flux distributions in
      neurons and small brain regions for which accurate metabolic flux measurements
      are not yet possible.

PMID- 30208079
TI  - Improving quantitative writing one sentence at a time.
AB  - Scientific writing, particularly quantitative writing, is difficult to master. To
      help undergraduate students write more clearly about data, we sought to
      deconstruct writing into discrete, specific elements. We focused on statements
      typically used to describe data found in the results sections of research
      articles (quantitative comparative statements, QC). In this paper, we define the
      essential components of a QC statement and the rules that govern those
      components. Clearly defined rules allowed us to quantify writing quality of QC
      statements (4C scoring). Using 4C scoring, we measured student writing gains in a
      post-test at the end of the term compared to a pre-test (37% improvement). In
      addition to overall score, 4C scoring provided insight into common writing
      mistakes by measuring presence/absence of each essential component. Student
      writing quality in lab reports improved when they practiced writing isolated QC
      statements. Although we observed a significant increase in writing quality in lab
      reports describing a simple experiment, we noted a decrease in writing quality
      when the complexity of the experimental system increased. Our data suggest a
      negative correlation of writing quality with complexity. We discuss how our data
      aligns with existing cognitive theories of writing and how science instructors
      might improve the scientific writing of their students.

PMID- 30208077
TI  - Neighbourhood child population density as a proxy measure for exposure to
      respiratory infections in the first year of life: A validation study.
AB  - BACKGROUND: Assessing exposure to infections in early childhood is of interest in
      many epidemiological investigations. Because exposure to infections is difficult
      to measure directly, epidemiological studies have used surrogate measures
      available from routine data such as birth order and population density. However,
      the association between population density and exposure to infections is unclear.
      We assessed whether neighbourhood child population density is associated with
      respiratory infections in infants. METHODS: With the Basel-Bern lung infant
      development study (BILD), a prospective Swiss cohort study of healthy neonates,
      respiratory symptoms and infections were assessed by weekly telephone interviews
      with the mother throughout the first year of life. Using population census data,
      we calculated neighbourhood child density as the number of children < 16 years of
      age living within a 250 m radius around the residence of each child. We used
      negative binomial regression models to assess associations between neighbourhood
      child density and the number of weeks with respiratory infections and adjusted
      for potential confounders including the number of older siblings, day-care
      attendance and duration of breastfeeding. We investigated possible interactions
      between neighbourhood child population density and older siblings assuming that
      older siblings mix with other children in the neighbourhood. RESULTS: The
      analyses included 487 infants. We found no evidence of an association between
      quintiles of neighbourhood child density and number of respiratory symptoms (p =
      0.59, incidence rate ratios comparing highest to lowest quintile: 1.15, 95%
      confidence interval: 0.90-1.47). There was no evidence of interaction with older
      siblings (p = 0.44). Results were similar in crude and in fully adjusted models.
      CONCLUSIONS: Our study suggests that in Switzerland neighbourhood child density
      is a poor proxy for exposure to infections in infancy.

PMID- 30208078
TI  - Predictive value of a diagnostic block in focal nerve injury with neuropathic
      pain when surgery is considered.
AB  - OBJECT: In patients with focal nerve injury and neuropathic pain cutting the
      nerve to obtain permanent pain reduction can be considered. Surgery is indicated
      only if a diagnostic nerve block provides temporary pain relief. We evaluated the
      predictive value of a block on the outcome of surgery. METHODS: In total, three
      blocks were performed at two week intervals. Patients were blinded to injections
      containing lidocaine 1% and a placebo was included. Surgery was offered
      regardless of the effect of the blocks. Twenty-four patients received 72 blocks.
      Sixteen patients opted for surgery, 5 patients refrained from surgery, and in 3
      the blocks provided permanent pain relief. The predictive ability of the block on
      the outcome of surgery was assessed by calculating the area under a Receiver
      Operating Characteristic curve (AUC). RESULTS: The AUC of the first lidocaine
      block was 0.35 with a 95% confidence interval from 0.077 to 0.62. At 95%
      confidence (two-sided), the AUC is less than 0.62, and hence the predictive
      ability of the block was poor. The outcome of the second lidocaine block and
      saline block did not change the conclusion of the first block. CONCLUSIONS: We
      conclude that the use of blocks to select patients for surgery should be
      critically appraised. PERSPECTIVE: A pain relieving response to one open block is
      currently considered mandatory before patients with focal nerve injury and
      neuropathic pain are offered surgery. Blinded blocks including a placebo show
      that responses for selection should be carefully interpreted because they may not
      be as predictive as generally presumed.

PMID- 30208080
TI  - Visual evoked potentials in offspring born to mothers with overweight, obesity
      and gestational diabetes.
AB  - BACKGROUND: Overweight, obesity, and gestational diabetes (GD) during pregnancy
      may negatively affect neurodevelopment in the offspring. However, the mechanisms
      are unclear and objective measures of neurodevelopment in infancy are scarce. We
      hypothesized that these maternal metabolic pathologies impair cortical visual
      evoked potentials (cVEPs), a proxy for visual and neuronal maturity. DESIGN: The
      PREOBE study included 331 pregnant women stratified into four groups; normal
      weight (controls), overweight, obesity, and GD (the latter including mothers with
      normal weight, overweight and obesity). In a subsample of the offspring at 3
      months (n = 157) and at 18 months (n = 136), we assessed the latencies and
      amplitudes of the P100 wave from cVEPs and calculated visual acuity. RESULTS: At
      3 months of age, visual acuity was significantly poorer in offspring born to GD
      mothers. At 18 months of age, there were no differences in visual acuity but
      infants born to GD mothers had significantly longer latencies of cVEPs when
      measured at 15', and 30' of arc. The group differences at 30' remained
      significant after confounder adjustment (mean [SD] 121.0 [16.0] vs. 112.6 [7.6]
      ms in controls, p = 0.007) and the most prolonged latencies were observed in
      offspring to GD mothers with concurrent overweight (128.9 [26.9] ms, p = 0.002)
      and obesity (118.5 [5.1] ms, p = 0.020). CONCLUSIONS: Infants born to mothers
      with GD, particularly those with concurrent overweight or obesity, have prolonged
      latencies of visual evoked potentials at 18 months of age, suggesting that this
      maternal metabolic profile have a long lasting, non-optimal, effect on infants'
      brain development.

PMID- 30208081
TI  - Early breeders choose differently - Refining measures of habitat quality for the
      yellow-bellied sapsucker (Sphyrapicus varius), a keystone species in the
      mixedwood boreal forest.
AB  - Despite the prevalent use of nest-site selection studies to define habitat
      quality for birds, many studies relying on use-availability analysis have found
      poor correlations between selected vegetation and reproductive success. Using 3
      years of data from northeastern British Columbia (2007-2009), we determined
      timing of breeding from hatching dates and contrasted the nest-site selection of
      earlier (n = 22) with later-nesting pairs (n = 36) of yellow-bellied sapsuckers
      (Sphyrapicus varius), because early breeders were expected to be more
      reproductively successful. We then compared these choices with those identified
      from use-availability analysis, and determined whether reproductive performance
      (fledgling production) was related to selected vegetation. None of the vegetation
      characteristics selected for nest sites from available vegetation predicted
      reproductive performance. Earlier-nesting pairs fledged more young on average
      than later breeders (4.41, SE = 0.18 versus 3.92, SE = 0.16), and chose less
      decayed aspen trees for nesting, that were surrounded on average by 3 times the
      number of food trees (paper birch, Betula papyrifera). Potential preference for
      birch trees was masked in the use-availability analysis, because the selection
      rate was dominated by the choices of the larger number of later-nesting pairs.
      Similarly, the majority (69%) of nest cavity entrances faced south, but earlier
      breeding pairs excavated northward-oriented cavities more frequently than did
      later breeding pairs, which strongly predicted their higher fledgling production.
      To our knowledge, our study is the first to compare the choices of early versus
      later breeders to test the efficacy of use-availability studies in defining
      habitat quality. We found that use-availability analysis was inadequate for
      determining vegetation characteristics related to reproductive performance. In
      contrast, measuring the distinct preferences of earlier breeders resulted in an
      improved ability to measure habitat quality and explain the spatial distribution
      of yellow-bellied sapsuckers, a keystone species of the mixedwood boreal forest.

PMID- 30208082
TI  - Quantifying the excess risk of infant mortality based on race/ethnicity at the
      county level to inform Michigan's home visiting outreach plans.
AB  - OBJECTIVE: Michigan's infant mortality rate is consistently higher than the
      national rate, with persistent and significant racial/ethnic disparities. In
      Michigan, nine counties account for more than 80% of all infant deaths. A home
      visiting program serving low-income, first-time mothers in high-risk communities
      is one strategy to reduce infant mortality. The objective of this study was to
      quantify the risk of infant mortality based on race/ethnicity within Michigan's
      highest-risk counties to guide outreach for home visiting services in these
      counties. METHODS: To maximize the efficiency of limited resources and to
      identify women at highest risk, we used decomposition to develop risk-based,
      county-specific estimates of excess infant deaths in nine Michigan counties using
      data from the 2007 to 2009 Michigan resident infant death file linked to the live
      birth/file. RESULTS: The sample size for these counties was 200,610 live births
      and 1,836 infant deaths and for the reference population it was 195,180 live
      births and 1,133 infant deaths The study found that excess mortality varies among
      populations at the county level when compared to the reference population of
      infants born to Michigan mothers who attained more than a high school education
      and were at least 20 years of age at the infant's birth. The excess risk of
      mortality was highest for African American infants in seven of the nine counties
      (56.5% to 132.8%) and for Hispanic infants (86.6%) and white infants (48.2%) in
      one county each. CONCLUSION: Even with a longstanding commitment and legal
      mandate to reduce disparities and with efforts to improve outreach into high-risk
      areas, disparities persist. An improved understanding of the racial/ethnic
      disparities within communities was useful to focus outreach efforts on reaching
      women at highest risk as part of subsequent program enrollment.

PMID- 30208083
TI  - Health status, difficulties, and desired health information and services for
      veterans with traumatic brain injuries and their caregivers: A qualitative
      investigation.
AB  - Traumatic brain injury (TBI) is considered the signature injury among military
      service member and Veterans who served in Operation Iraqi Freedom and Operation
      Enduring Freedom with over 360,000 individuals sustaining a first-time TBI in the
      military. These service members and Veterans, and their caregiver(s), must
      navigate multiple health systems and find experts across many fields of expertise
      to recover and optimize functionality. Twenty-two individuals, 10 caregivers of
      Veterans with TBI, 12 Veterans with TBI, participated in semi-structured
      interviews. Responses were coded using NVivo. Participants from both groups
      reported difficulties finding community supportive services (support groups) in
      local communities. Most participants identified the need for an advocate or point
      person to help guide them to needed services and provide ongoing support in the
      post-acute health care recovery phase. Caregivers and Veterans desired a more
      personalized recovery plan from their medical professionals. When describing
      their ideal health information and services model most identified interactivity
      and twenty-four-hour availability as essential components. To provide Veterans
      and caregivers with optimal support and resources to navigate a complicated
      health services system, advocates and personalized care plans are needed. Future
      research should examine the feasibility and cost-effectiveness of these services.

PMID- 30208085
TI  - Effectiveness of a learning support program for respiratory physical assessment:
      A quasi-experimental study.
AB  - BACKGROUND: Although the need for physical assessment in home nursing care has
      been shown, little research has examined the development of visiting nurses'
      physical assessment capabilities. OBJECTIVES: This study aimed to evaluate the
      effectiveness of a learning support program to help working visiting nurses
      utilize their respiratory physical assessment skills. DESIGN: This study used a
      quasi-experimental design of two groups with pre-test, post-test measurements of
      training and follow-up test 8 weeks practice in their work place after the
      training. METHODS: 57 currently working visiting nurses were assigned to 1 of 2
      groups: a control group in which nurses would not receive any special support
      after respiratory physical assessment training, and an experimental group in
      which nurses would receive support to utilize the knowledge and skills they had
      learned during the training. RESULTS: The average practical examination score was
      significantly higher after the training. In the experimental group, the average
      score 8 weeks after training was not significantly higher than that obtained just
      after training. Further, after 8 weeks, the experimental group's average score
      was not significantly higher than that of the control group. Practice evaluation
      scores obtained by an investigation of daily clinical practice were not
      significantly higher seventh weeks compared to third weeks after training for
      either the experimental or control groups. Seventh weeks after training, the
      average practice evaluation score of the experimental group was significantly
      higher than that of control groups. The mean learning support program
      satisfaction score was higher among the experimental group than the control
      group. CONCLUSIONS: The results suggested that support from others was effective
      in maintaining motivation for learning and making use in the regular practice of
      the knowledge and skills acquired in the respiratory physical assessment
      training.

PMID- 30208084
TI  - Aetiology of viral hepatitis among jaundiced patients presenting to a tertiary
      hospital in Ghana.
AB  - BACKGROUND: Viral hepatitis continues to play significant role in causing
      morbidity and mortality in sub-Saharan Africa. Apart from the few population
      based studies available, not many have investigated the burden of these viruses
      in jaundiced patients. Among the few studies, hepatitis E is the least studied
      among jaundiced patients. This study was aimed at describing the frequency,
      distribution and risk of the different hepatitis viruses among jaundiced patients
      reporting to the second largest teaching hospital in Ghana. METHODS: From
      November, 2015 to April, 2016, a cross-sectional study was conducted among
      jaundiced patients attending the Komfo Anokye Teaching Hospital. Between 3-5 ml
      of blood was collected from each patient and screened for viral hepatitis agents
      using both serologic and molecular-based assays. RESULTS: In the 155 patients
      recruited, hepatitis B was the most prevalent [54.2% (95% CI = 46.0%-62.2%)]
      followed by hepatitis E [32.9% (95% CI = 25.6-40.9%)]. Most cases of hepatitis E
      occurred as co-infections with hepatitis B (18%), with the predominant clinical
      feature being hepatocellular carcinoma. Risk factor variable analysis showed
      middle and older aged individuals were more at risk of hepatitis B exposure
      whereas younger age groups (<18 years) were more at risk of hepatitis E virus
      infection. CONCLUSION: Hepatitis viruses are still important in the viral
      aetiology of jaundice in Ghana. Hepatitis B and hepatitis E co-infections could
      play significant roles in causing severe disease. A more aggressive approach
      needs to be adopted in order to reduce the morbidity and mortality associated
      with hepatitis causing viruses in Ghana and other developing countries.

PMID- 30208086
TI  - Prevalence and factors associated with self-reported kidney disease among Serbian
      adults: Results of 2013 National Health Survey.
AB  - BACKGROUND: Data from developing countries on the rates of kidney disease are
      scarce. The study aimed to estimate population-based prevalence of self-reported
      kidney disease (SRKD) in Serbia, describe co-occurrence of chronic
      diseases/conditions/functional limitations in respondents with SRKD and explore
      association between SRKD and possible risk factors. METHODS: We performed a
      secondary analysis of 2013 National Health Survey data. Data on a total of 14,587
      respondents aged 15 years or older were analyzed using means of descriptive
      statistics, principal component analysis and logistic regression analysis.
      RESULTS: Out of all study respondents, 5.6% (95%CI 5.2-6.0) reported presence of
      kidney disease. Prevalence of all analyzed morbidities and functional limitations
      was higher in respondents with SRKD, and they had 8 times higher likelihood of
      being diagnosed with cirrhosis, 6.3 times higher likelihood of being diagnosed
      with urinary incontinence, more than 3 times higher likelihood of being diagnosed
      with degenerative disorder of bone and joint system. For cardiovascular diseases
      we obtained odds ratios (ORs) from 2.27 (95%CI 2.32-3.44) for heart attack to
      2.95 (95%CI 2.43-3.57) for coronary heart disease. Number of co-occurrence
      patterns of kidney and other chronic diseases/conditions varied depending on
      inclusion of obesity in models. Logistic regression analysis showed that age
      explained most part of variability in the prevalence of SRKD and in the
      prevalence of two morbidities in respondents with SRKD, whereas the presence of
      three or more morbidities were associated with female gender, aging and low
      education level. CONCLUSIONS: Our study provided evidence that the presence of
      kidney disease was significantly associated with socio-demographic, lifestyle
      characteristics and a number of morbidities in Serbia. There is a need for
      integrated care and public health interventions, tackling management of NCDs and
      their risk factors. Detailed well-designed studies, as part of cost-effective
      preventive approach, are needed for chronic kidney disease screening.

PMID- 30208088
TI  - The effect of exposure to high altitude and low oxygen on intestinal microbial
      communities in mice.
AB  - This experiment was conducted to investigate the effect of exposure to high
      altitude and low oxygen on intestinal microbial communities using mice as an
      animal model. Fecal microbiota from mice housed in a control environment
      representing 2,200 meters (NC group) above sea level with 16% Oxygen and mice
      that were placed in a hypobaric chamber representing 5000 meters (HC group) above
      sea level with 11% Oxygen for 30 days, were analyzed by the HiSeq Illumina
      sequencing platform. The results showed a significant difference in beta
      diversity observed between the two groups, while no significant difference was
      observed in alpha diversity. Compared with the NC group, the relative abundance
      of class Epsilonproteobacteria, phlym Actinobacteria, class Erysipelotrichia and
      genus Helicobacter were significantly lower (P<0.05), while the relative
      abundance of genus Alistipes was increased in the HC group; Phenotypic analysis
      showed no significant difference in aerobic, anaerobic, facultatively anaerobic,
      potentially pathogenic, stress tolerant, mobile element, biofilms formation, gram
      negative and gram positive between HC group and NC group; Functional analysis
      results showed significant differences in 34 gene functional metabolic pathways
      (carbohydrate digestion and absorption, energy metabolism, arachidonic acid
      metabolism, flavonoid biosynthesis, RIG-I-like receptor signaling pathway, etc)
      between HC group and NC group. Together, these findings suggest that exposure to
      high altitude and low oxygen had the potential to change the intestinal microbial
      communities, which potentially may modulate metabolic processes in mice.

PMID- 30208087
TI  - Which obesity phenotypes predict poor health-related quality of life in adult men
      and women? Tehran Lipid and Glucose Study.
AB  - PURPOSE: This study aimed to explore the association between different obesity
      phenotypes and health-related quality of life (HRQoL) among Tehranian men and
      women. METHODS: The participants of this study were 2880 healthy adults (aged>19
      years) who participated in Tehran Lipid and Glucose Study (TLGS). To obtain socio
      demographic and HRQoL information, participants were interviewed by trained
      interviewers and were stratified by body mass index categories and metabolic
      status. Dysmetabolic status was defined as having either metabolic syndrome or
      diabetes according to the Joint Interim Statement definition and American
      Diabetes Association. Poor HRQoL was defined as the first quartile of HRQoL
      scores and logistic regression analysis was used to compare sex-specific odds
      ratios. RESULTS: Mean age of participants was 47.7+/-15.6 and 47.8+/-14.2 years
      in men and women respectively. The most and the least common obesity phenotypes
      were overweight-normal metabolic status and normal weight-dysmetabolic status,
      respectively. Only mean scores for physical HRQoL were significantly different
      among obesity phenotypes in both men and women (p<0.05). In addition, after
      adjusting for age, marital status, level of education, job status and physical
      activity, the odds of reporting poor physical HRQoL was significantly higher in
      men (OR: 1.960, 95% CI: 1.037-3.704; p<0.05) and women (OR: 2.887, 95% CI: 1.674
      4.977; p<0.001) with obese-dysmetabolic status, compared to their counterparts
      with normal weight-normal metabolic status. However, except for overweight-normal
      metabolic women, who were less likely to report poor mental HRQoL (OR: 0.638, 95%
      CI: 0.415-0.981; p<0.05), none of the phenotypes were associated with poor mental
      HRQoL in either gender. CONCLUSIONS: Compared to those with normal weight normal
      metabolic status, only obese dysmetabolic individuals were more likely to report
      poor physical HRQoL in both genders.

PMID- 30208089
TI  - Pollen trapping and sugar syrup feeding of honey bee (Hymenoptera: Apidae)
      enhance pollen collection of less preferred flowers.
AB  - Pear (Pyrus bretschneideri) is characterized by being self-incompatible and
      dependent on cross-pollination to set fruit. Honeybee (Apis mellifera) is
      considered the most important pollinator of pear. Nevertheless, limited pollen
      transfer has been cited as the main cause of poor fruit set in many pear
      orchards. Here, we tested the following hypotheses: (i) colony manipulations
      increase the pollen collection tendency of honeybees and (ii) the proportion of
      pollen loads being returned to the hive is from the target plant. The technique
      reliably and rapidly estimates the pollination of honeybees tested under
      different colony manipulations: (1) using pollen trapping (PT); (2) PT with sugar
      syrup feeding (SS) (PTSS); (3) SS alone and (4) control without PT and SS. The
      results clearly show that the pollen collection of honeybees during the
      experiment was significantly affected (P < 0.05) by colony manipulations. The
      mean amount of pollen harvested daily was higher for PTSS (19.4 g) and PT (16.4
      g) than for SS (12.85 g) and control (8.7 g) colonies. Therefore, PTSS was the
      most effective treatment for increasing pear pollen collection; other treatments
      such as PT and SS could also be useful. This study was important for determining
      how the behavior of honeybee colonies is shaped through colony manipulation to
      enhance pollen collection of less preferred pear flowers, which is critical when
      pollination is required.

PMID- 30208090
TI  - Insights into the life strategy of the common marine diatom Chaetoceros
      peruvianus Brightwell.
AB  - Chaetoceros peruvianus is a marine diatom species with circumglobal distribution.
      While frequently observed, it appears never to dominate the marine phytoplankton
      community hence it can be characterized as a rather opportunistic, generalistic
      species. Here we present ecological interpretations from a long-term data set on
      marine microphytoplankton in the northern Adriatic Sea, where the abundancies and
      relative contributions of C. peruvianus were observed along a set of steep
      ecological gradients. Limited supply of dissolved inorganic phosphate was
      identified as the driving ecological factor for this ecosystem. In parallel C.
      peruvianus was cultivated in monoclonal cultures and its morphological and
      physiological reaction to replete and phosphorus depleted medium was analysed. C.
      peruvianus reacted to phosphorus depletion by an increase in cell height and
      length as well as thickness and length of setae. This morphological reaction
      included an increase in cellular volume and calculated carbon content.
      Additionally, it represents the transition between two described morphological
      varieties, C. peruvianus and C. peruvianus var. robusta. C. peruvianus showed a
      significant induction of extracellular alkaline phosphatase activity if grown in
      phosphate depleted medium. Microscopical analysis demonstrated this activity to
      be located exclusively on the setae of the cells.

PMID- 30208091
TI  - Transfer of Cry1F from Bt maize to eggs of resistant Spodoptera frugiperda.
AB  - The intergenerational transfer of plant defense compounds by aposematic insects
      is well documented, and since 2006, has been shown for Cry toxins. Cry toxins are
      proteins naturally produced by the soil bacterium Bacillus thuringiensis (Bt) and
      its genes have been expressed in plants to confer insect pest resistance. In this
      work we tested if non-aposematic larvae of a major maize pest, Spodoptera
      frugiperda, with resistance to Cry1F, could transfer Cry1F from a genetically
      engineered maize variety to their offspring. Resistant 10-day-old larvae that fed
      on Cry1F Bt maize until pupation were sexed and pair-mated to produce eggs. Using
      ELISA we found that Cry1F was transferred to offspring (1.47-4.42 ng Cry1F/10
      eggs), a toxin concentration about 28-83 times less than that detected in Cry1F
      Bt maize leaves. This occurred when only one or both sexes were exposed, and more
      was transferred when both parents were exposed, with transitory detection in the
      first five egg masses. This work is an unprecedented demonstration that a non
      aposematic, but resistant, species can transfer Cry1F to their offspring when
      exposed to Bt host plant leaves as immatures.

PMID- 30208092
TI  - Item response theory evaluation of the biomedical scale of the Pain Attitudes and
      Beliefs Scale.
AB  - OBJECTIVES: The assessment of health care professionals' attitudes and beliefs
      towards musculoskeletal pain is essential because they are key determinants of
      their clinical practice behaviour. The Pain Attitudes and Beliefs Scale (PABS)
      biomedical scale evaluates the degree of health professionals' biomedical
      orientation towards musculoskeletal pain and was never assessed using item
      response theory (IRT). This study aimed at assessing the psychometric performance
      of the 10-item biomedical scale of the PABS scale using IRT. METHODS: Two cross
      sectional samples (BeBack, n = 1016; DABS; n = 958) of health care professionals
      working in the UK were analysed. Mokken scale analysis (nonparametric IRT) and
      common factor analysis were used to assess dimensionality of the instrument.
      Parametric IRT was used to assess model fit, item parameters, and local
      reliability (measurement precision). RESULTS: Results were largely similar in the
      two samples and the scale was found to be unidimensional. The graded response
      model showed adequate fit, covering a broad range of the measured construct in
      terms of item difficulty. Item 3 showed some misfit but only in the DABS sample.
      Some items (i.e. 7, 8 and 9) displayed remarkably higher discrimination
      parameters than others (4, 5 and 10). The scale showed satisfactory measurement
      precision (reliability > 0.70) between theta values -2 and +3. DISCUSSION: The 10
      item biomedical scale of the PABS displayed adequate psychometric performance in
      two large samples of health care professionals, and it is suggested to assess
      group-level professionals degree of biomedical orientation towards
      musculoskeletal pain.

PMID- 30208093
TI  - Effect of sowing date and water availability on growth of plants of chia (Salvia
      hispanica L) established in Chile.
AB  - From 2010 to 2014 two trials were performed to assess the effect of sowing date
      (SD1, SD2) and irrigation treatments (IT1, IT2) on the growth of chia in central
      Chile, measuring leaf area (LA) and dry matter (DM) as primary parameters and
      relative growth rate (RGR), net assimilation rate (NAR), leaf weight ratio (LWR),
      crop growth rate (CGR) and specific leaf weight (SLW) as secondary parameters.
      Both LA and DM reached maximum values between 640 and 1150 accumulated degree
      days (ADD). However, LA and DM were 25% greater for sowing dates than for
      available water. Flowering date was also not affected by sowing date or water
      availability; plants flowered at 1140 and 942 ADD in SD1 and SD2 respectively,
      and at 499 ADD in the water availability trial. Sowing date had a significant
      effect on RGR 0.15 g g-1 d-1 for SD1 and 0.12 g g-1 d-1 for SD2 at 410 ADD.
      Greater water availability increased RGR by 60% compared to stressed plants,
      however NAR was similar between sowing dates with a tendency to greater values in
      SD2 plants; maximum values were recorded at 514 ADD in IT1 and IT2, with a
      tendency toward higher values in IT1. Thus, the primary growth variables LA, DM
      and flowering are genetically determined. However, the derived growth variables
      RGR, LWR, NAR, CGR and SLW were affected by sowing date and water availability,
      with significant differences at p<= 0.05. The results showed that the sowing date
      and water availability influence significantly the growth parameters. The
      physiological component (NAR) show a strong influence on the growth rate of the
      chia (RGR), above the morphological component (SLW and LAR).

PMID- 30208094
TI  - Molecular strain typing of the yaws pathogen, Treponema pallidum subspecies
      pertenue.
AB  - Yaws is a neglected tropical disease caused by the bacterium Treponema pallidum
      subspecies pertenue. The disease primarily affects children under 15 years of age
      living in low socioeconomic conditions in tropical areas. As a result of a
      renewed focus on the disease owing to a recent eradication effort initiated by
      the World Health Organization, we have evaluated a typing method, adapted from
      and based on the enhanced Centers for Disease Control and Prevention typing
      method for T. pallidum subsp. pallidum, for possible use in epidemiological
      studies. Thirty DNA samples from yaws cases in Vanuatu and Ghana, 11 DNA samples
      extracted from laboratory strains, and 3 published genomic sequences were fully
      typed by PCR/RFLP analysis of the tpr E, G, and J genes and by determining the
      number of 60-bp repeats within the arp gene. Subtyping was performed by
      sequencing a homonucleotide "G" tandem repeat immediately upstream of the rpsA
      gene and an 84-bp region of tp0548. A total of 22 complete strain types were
      identified; two strain types in clinical samples from Vanuatu (5q11/ak and
      5q12/ak), nine strain types in clinical samples from Ghana (3q12/ah, 4r12/ah,
      4q10/j, 4q11/ah, 4q12/ah, 4q12/v, 4q13/ah, 6q10/aj, and 9q10/ai), and twelve
      strain types in laboratory strains and published genomes (2q11/ae, 3r12/ad,
      4q11/ad, 4q12/ad, 4q12/ag, 4q12/v, 5r12/ad, 6r12/x, 6q11/af, 10q9/r, 10q12/r, and
      12r12/w). The tpr RFLP patterns and arp repeat sizes were subsequently verified
      by sequencing analysis of the respective PCR amplicons. This study demonstrates
      that the typing method for subsp. pallidum can be applied to subsp. pertenue
      strains and should prove useful for molecular epidemiological studies on yaws.

PMID- 30208095
TI  - Self-perceived competence in early diagnosis of cervical cancer among recently
      graduated physicians from Lima, Peru.
AB  - OBJECTIVE: To assess the prevalence of recently graduated physicians who
      perceived themselves as adequately competent to perform Papanicolaou (PAP),
      Visual Inspection with Acetic Acid (VIA), and Visual Inspection with Lugol's
      Iodine (VILI); and study its associated factors, in Lima, Peru. METHODS: This
      cross-sectional study evaluated recently graduated physicians from Lima, Peru.
      Physicians were considered to perceive themselves as adequately competent if they
      had answered, "agree" or "strongly agree" when asked if they were competent
      enough to perform these screening tests. To evaluate the associated factors,
      prevalence ratios (PR) were calculated using Poisson regressions with robust
      variance. RESULTS: Only 367/432 (86.2%) physicians perceived themselves as
      adequately competent to perform PAP, 257 (60.5%) to perform VIA, and 247 (58.1%)
      to perform VILI. Physicians who performed their gynecology/obstetric clerkship at
      hospitals from the police or armed forces had a higher proportion of perceiving
      themselves as adequately competent to perform VIA and VILI. CONCLUSIONS: Nine out
      of ten physicians perceived themselves as adequately competent to perform PAP,
      while six out of ten to perform VIA or VILI. The health care system in which the
      physicians performed their clerkship was associated with the prevalence of
      adequate self-perceived competence for performing VIA and VILI.

PMID- 30208096
TI  - A Hybrid Geometric Spatial Image Representation for scene classification.
AB  - The recent development in the technology has increased the complexity of image
      contents and demand for image classification becomes more imperative. Digital
      images play a vital role in many applied domains such as remote sensing, scene
      analysis, medical care, textile industry and crime investigation. Feature
      extraction and image representation is considered as an important step in scene
      analysis as it affects the image classification performance. Automatic
      classification of images is an open research problem for image analysis and
      pattern recognition applications. The Bag-of-Features (BoF) model is commonly
      used to solve image classification, object recognition and other computer vision
      based problems. In BoF model, the final feature vector representation of an image
      contains no information about the co-occurrence of features in the 2D image
      space. This is considered as a limitation, as the spatial arrangement among
      visual words in image space contains the information that is beneficial for image
      representation and learning of classification model. To deal with this,
      researchers have proposed different image representations. Among these, the
      division of image-space into different geometric sub-regions for the extraction
      of histogram for BoF model is considered as a notable contribution for the
      extraction of spatial clues. Keeping this in view, we aim to explore a Hybrid
      Geometric Spatial Image Representation (HGSIR) that is based on the combination
      of histograms computed over the rectangular, triangular and circular regions of
      the image. Five standard image datasets are used to evaluate the performance of
      the proposed research. The quantitative analysis demonstrates that the proposed
      research outperforms the state-of-art research in terms of classification
      accuracy.

PMID- 30208098
TI  - Clinical value of delayed 18F-FDG PET/CT for predicting nipple-areolar complex
      involvement in breast cancer: A comparison with clinical symptoms and breast MRI.
AB  - OBJECTIVE: We aimed to evaluate the predictive value of delayed 18F-FDG PET/CT
      for identifying malignancies involved in the nipple-areolar complex (NAC) in
      comparison with clinical symptoms and breast MRI. METHODS: We enrolled 90
      patients who underwent preoperative delayed 18F-FDG PET/CT and MRI between
      October 2015 and May 2017. We calculated the NAC-Standardized uptake value ratio
      (SUVR) using the following formula: maximum SUV (SUVmax) of the NAC in the
      malignant breast /SUVmax of the NAC in the contralateral normal breast on early
      (NAC-SUVRearly) and delayed (NAC-SUVRdelay) phase images. MRI was used to measure
      the distance between the tumor and NAC and to analyze NAC enhancement patterns.
      Univariate and multivariate analyses were performed to identify significant
      predictive factors for NAC involvement. RESULTS: Seventeen patients were
      confirmed to have pathologic NAC involvement. NAC symptoms (p = 0.009), tumor
      multiplicity (p = 0.006), NAC-SUVRdelay (> 1.23, p = 0.007), and MRI-based tumor
      to-NAC distance (<= 22.0 mm, p = 0.003) were independent predictive factors for
      NAC involvement. Ten of 76 patients with no clinical NAC symptoms had NAC
      malignancy. Tumor multiplicity (p = 0.009), tumor-to-NAC distance (<= 20.0 mm, p
      = 0.014)), and NAC-SUVRdelay (> 1.23, p = 0.018) had independent predictive value
      for NAC involvement. CONCLUSIONS: Delayed 18F-FDG PET/CT is a useful modality for
      predicting NAC involvement in breast cancer patients whether or not NAC symptoms
      are present.

PMID- 30208097
TI  - The HIV patient profile in 2013 and 2003: Results from the Greek AMACS cohort.
AB  - Combined Antiretroviral therapy (cART) has improved life-expectancy of people
      living with HIV (PLHIV) but as they age, prevalence of chronic non-AIDS related
      comorbidities may increase. We study the evolution of HIV-disease markers and
      comorbidities' prevalence in PLHIV in Greece. Two cross-sectional analyses (2003
      and 2013) on data from the AMACS cohort were performed. Comparisons were based on
      population average models and were repeated for subjects under follow-up at both
      2003 and 2013. 2,403 PLHIV were identified in 2003 and 4,910 in 2013 (1,730
      contributing for both cross-sections). Individuals in 2013 were on average older,
      diagnosed/treated for HIV for longer, more likely to be on cART, virologically
      suppressed, and with higher CD4 counts. Chronic kidney disease, dyslipidemia and
      hypertension prevalence increased over time. There was an increase in
      prescription of lipid-lowering treatment (3.5% in 2003 vs. 7.7% 2013, p<0.001).
      Among 220 and 879 individuals eligible for Framingham 10-year Event Risk
      calculation, the proportion of patients in the high-risk group (>20%) increased
      from 18.2% to 22.2% (p = 0.002). Increase in the prevalence of comorbidities was
      more pronounced in the subset of patients who were followed in both 2003 and
      2013. The increased availability and uptake of cART led to significant
      improvements in the immuno-virological status of PLHIV in Greece, but they aged
      alongside an increase in prevalence of non-AIDS related comorbidities. These
      results highlight the need for appropriate monitoring, optimal cART selection and
      long-term management and prevention strategies for such comorbidities.

PMID- 30208099
TI  - Sinus node dysfunction after surgical atrial fibrillation ablation with
      concomitant mitral valve surgery: Determinants and clinical outcomes.
AB  - OBJECTIVE: We sought to investigate determinants and prognosis of sinus node
      dysfunction (SND) after surgical ablation of atrial fibrillation (AF) with
      concomitant mitral valve (MV) surgery. A total of 202 patients who underwent
      surgical AF ablation with concomitant MV surgery were studied. STUDY DESIGN AND
      SETTING: SND was defined as electrocardiographic manifestations, such as
      junctional bradycardia, symptomatic sick sinus syndrome, or symptomatic sinus
      bradycardia, 7 days after surgery. Baseline clinical and echocardiographic
      characteristics, rhythm outcomes [AF recurrence or permanent pacemaker (PM)
      implantation] at 6 and 12 months, and clinical outcomes were compared between
      patients without SND (n = 165) and those with SND (n = 37) after surgery.
      RESULTS: Patients with SND showed a significantly larger left atrial volume index
      (LAVI) and a higher right ventricular systolic pressure than those without SND.
      In addition, there was a higher likelihood for AF recurrence and PM implantation
      in patients with SND than in those without SND. Although clinical outcomes did
      not differ between the two groups, patients with SND had a significantly longer
      length of hospital stay (p<0.001). In a multivariate analysis, preoperative LAVI
      was a structural risk factor for SND [hazard ratio (HR): 1.126 per 10 mL/m2; 95%
      confidence interval (CI): 1.0206-1.236; p = 0.001]. An LAVI cut-off value of 105
      mL/m2 showed significant predictive power for SND [sensitivity: 62%; specificity:
      64%; area under the curve (AUC): 0.678; p = 0.002]. CONCLUSIONS: In conclusion,
      preoperative LA size was a structural risk factor for SND after surgical AF
      ablation during MV surgery. SND was associated with an increased risk for AF
      recurrence and implantation of permanent PM in patients undergoing concomitant
      surgical ablation of AF with MV surgery.

PMID- 30208100
TI  - Keratinocyte stem cells are more resistant to UVA radiation than their direct
      progeny.
AB  - The epidermis undergoes constant renewal during its lifetime. This is possible
      due to a special population of keratinocyte stem cells (KSCs) located at the
      basal layer. These cells are surrounded by their direct progeny, keratinocyte
      progenitors or transient amplifying cells (TAs), which arise from cell division.
      Skin is exposed every day to sun radiation; in particular, UVA radiation
      penetrates through the epidermis and induces damage to KSCs and TAs. Although
      keratinocytes in the basal layer are the most likely skin carcinomas and/or
      photoaging cells of origin, surprisingly few studies have addressed the specific
      responses of these cells to UV radiation. In this study, we showed for the first
      time that keratinocyte stem cells were more resistant to UVA irradiation than
      their direct progeny, transient amplifying cells. Using both the MTT assay and
      clonogenic assay, we found that KSCs were more photo-resistant compared to TAs
      after exposure to different doses of UVA (from 0 to 50 J/cm2). Moreover, KSCs had
      a greater ability to reconstruct human epidermis (RHE) after UVA exposure
      compared with TAs. Finally, investigations of DNA repair using the comet assay
      showed that DNA single-strand breaks and thymine dimers were repaired quicker and
      more efficiently in KSCs compared with TAs. In a previous work, we showed that
      the same stem cell population was more resistant to ionizing radiation, another
      carcinogenic agent. Collectively, our results combined with other observations
      demonstrate that keratinocyte stem cells, which are responsible for epidermal
      renewal throughout life, are equipped with an efficient arsenal against several
      genotoxic agents. Our future work will try to identify the factors or signaling
      pathways that are responsible for this differential photo-sensitivity and DNA
      repair capacity between KSCs and TAs.

PMID- 30208101
TI  - A novel method of using Deep Belief Networks and genetic perturbation data to
      search for yeast signaling pathways.
AB  - Perturbing a signaling system with a serial of single gene deletions and then
      observing corresponding expression changes in model organisms, such as yeast, is
      an important and widely used experimental technique for studying signaling
      pathways. People have developed different computational methods to analyze the
      perturbation data from gene deletion experiments for exploring the signaling
      pathways. The most popular methods/techniques include K-means clustering and
      hierarchical clustering techniques, or combining the expression data with
      knowledge, such as protein-protein interactions (PPIs) or gene ontology (GO), to
      search for new pathways. However, these methods neither consider nor fully
      utilize the intrinsic relation between the perturbation of a pathway and
      expression changes of genes regulated by the pathway, which served as the main
      motivation for developing a new computational method in this study. In our new
      model, we first find gene transcriptomic modules such that genes in each module
      are highly likely to be regulated by a common signal. We then use the expression
      status of those modules as readouts of pathway perturbations to search for up
      stream pathways. Systematic evaluation, such as through gene ontology enrichment
      analysis, has provided evidence that genes in each transcriptomic module are
      highly likely to be regulated by a common signal. The PPI density analysis and
      literature search revealed that our new perturbation modules are functionally
      coherent. For example, the literature search revealed that 9 genes in one of our
      perturbation module are related to cell cycle and all 10 genes in another
      perturbation module are related by DNA damage, with much evidence from the
      literature coming from in vitro or/and in vivo verifications. Hence, utilizing
      the intrinsic relation between the perturbation of a pathway and the expression
      changes of genes regulated by the pathway is a useful method of searching for
      signaling pathways using genetic perturbation data. This model would also be
      suitable for analyzing drug experiment data, such as the CMap data, for finding
      drugs that perturb the same pathways.

PMID- 30208102
TI  - Correction: Predictors of death including quality of positive pressure
      ventilation during newborn resuscitation and the relationship to outcome at seven
      days in a rural Tanzanian hospital.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0202641.].

PMID- 30208104
TI  - Correction: Monitoring for myelopathic progression with multiparametric
      quantitative MRI.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0195733.].

PMID- 30208103
TI  - Para-cresol production by Clostridium difficile affects microbial diversity and
      membrane integrity of Gram-negative bacteria.
AB  - Clostridium difficile is a Gram-positive spore-forming anaerobe and a major cause
      of antibiotic-associated diarrhoea. Disruption of the commensal microbiota, such
      as through treatment with broad-spectrum antibiotics, is a critical precursor for
      colonisation by C. difficile and subsequent disease. Furthermore, failure of the
      gut microbiota to recover colonisation resistance can result in recurrence of
      infection. An unusual characteristic of C. difficile among gut bacteria is its
      ability to produce the bacteriostatic compound para-cresol (p-cresol) through
      fermentation of tyrosine. Here, we demonstrate that the ability of C. difficile
      to produce p-cresol in vitro provides a competitive advantage over gut bacteria
      including Escherichia coli, Klebsiella oxytoca and Bacteroides thetaiotaomicron.
      Metabolic profiling of competitive co-cultures revealed that acetate, alanine,
      butyrate, isobutyrate, p-cresol and p-hydroxyphenylacetate were the main
      metabolites responsible for differentiating the parent strain C. difficile
      (630Deltaerm) from a defined mutant deficient in p-cresol production. Moreover,
      we show that the p-cresol mutant displays a fitness defect in a mouse relapse
      model of C. difficile infection (CDI). Analysis of the microbiome from this mouse
      model of CDI demonstrates that colonisation by the p-cresol mutant results in a
      distinctly altered intestinal microbiota, and metabolic profile, with a greater
      representation of Gammaproteobacteria, including the Pseudomonales and
      Enterobacteriales. We demonstrate that Gammaproteobacteria are susceptible to
      exogenous p-cresol in vitro and that there is a clear divide between bacterial
      Phyla and their susceptibility to p-cresol. In general, Gram-negative species
      were relatively sensitive to p-cresol, whereas Gram-positive species were more
      tolerant. This study demonstrates that production of p-cresol by C. difficile has
      an effect on the viability of intestinal bacteria as well as the major
      metabolites produced in vitro. These observations are upheld in a mouse model of
      CDI, in which p-cresol production affects the biodiversity of gut microbiota and
      faecal metabolite profiles, suggesting that p-cresol production contributes to C.
      difficile survival and pathogenesis.

PMID- 30208105
TI  - A longitudinal evaluation of psychosocial changes throughout orthognathic
      surgery.
AB  - BACKGROUND: Jaw correction surgery can cause significant psychosocial impacts on
      patients. This prospective study investigated the longitudinal changes of
      psychosocial characteristics of patients with dentofacial deformities after jaw
      correction surgery and the factors that predict the psychological resilience in
      Hong Kong Chinese undergoing jaw correction surgery. METHODS: A longitudinal
      cohort study was conducted on 92 Hong Kong Chinese patients (32 males, 60
      females; mean age = 24.75 +/- 5.65 years), who had jaw correction surgery as
      treatment for their dentofacial deformities, from 1st June 2011 to 30th June
      2015. Self-completed psychological inventories including Brief Symptom Inventory,
      Life Orientation Test, and the Adult Trait Hope Scale were used to measure
      distress, optimism, and hope levels respectively. Patients completed the
      inventories in five time points: the surgical consent signing day (usually two to
      three months before the surgery) (T1); one day before operation (T2), first to
      second post-operative week (T3), third post-operative month (T4) and sixth post
      operative month (T5). RESULTS: Latent class growth analysis revealed two outcome
      trajectory classes: a resilience trajectory (n = 45, 48.9%) and a chronic
      dysfunction trajectory (n = 14, 15.2%). Another 33 (35.9%) showed erratic
      trajectory patterns that would not be classified into any categories. The
      psychological distress levels of patients in the resilience trajectory group, on
      average, were below the clinical threshold of the Brief Symptom Inventory at all
      time points. However, the opposite result was obtained for patients in the
      chronic dysfunctional group. Patients exhibiting a resilience trajectory pattern,
      when compared to those showing a chronic dysfunction pattern, had higher optimism
      (t(57) = 3.69, p < .0001) and hope (t(57) = 2.46, p < .05) levels at T1. Logistic
      regression analyses were conducted to compare the relative power of optimism and
      hope levels at T1 to predict resilience or chronic dysfunctional group
      membership. A test of the full model against a constant only model was
      statistically significant (chi2(2) = 24.096, p < .01). Preoperative baseline
      optimism (B = -.276, p < .05) but not hope (B = -.25, ns) was a significant
      variable to classify the outcome trajectories for psychological distress.
      CONCLUSIONS: Most patients were resilient to dentofacial deformities jaw
      correction surgery. About 15% exhibited a chronic distress pattern. An optimistic
      view about the surgery may enhance resilience. Pre-surgical counselling or
      educational sessions to facilitate a realistic positive outlook about the
      operation would be beneficial.

PMID- 30208106
TI  - Absence of spatial genetic structure in common dentex (Dentex dentex Linnaeus,
      1758) in the Mediterranean Sea as evidenced by nuclear and mitochondrial
      molecular markers.
AB  - The common dentex, Dentex dentex, is a fish species which inhabits marine
      environments in the Mediterranean and Northeast Atlantic regions. This is an
      important species from an ecological, economic and conservation perspective,
      however critical information on its population genetic structure is lacking. Most
      samples were obtained from the Mediterranean Sea (17 sites) with an emphasis
      around Corsica (5 sites), plus one Atlantic Ocean site. This provided an
      opportunity to examine genetic structuring at local and broader scales to provide
      science based data for the management of fishing stocks in the region. Two
      mitochondrial regions were examined (D-loop and COI) along with eight
      microsatellite loci. The COI data was combined with publicly available sequences
      and demonstrated past misidentification of common dentex. All markers indicated
      the absence of population genetic structure from the Bay of Biscay to the eastern
      Mediterranean Sea. Bayesian approaches, as well as the statistical tests
      performed on the allelic frequencies from microsatellite loci, indicated low
      differentiation between samples; there was only a slight (p = 0.05) indication of
      isolation by distance. Common dentex is a marine fish species with a unique
      panmictic population in the Mediterranean and likely in the Atlantic Ocean as
      well.

PMID- 30208107
TI  - Dimerization misalignment in human glutamate-oxaloacetate transaminase variants
      is the primary factor for PLP release.
AB  - The active form of vitamin B6, pyridoxal 5'-phosphate (PLP), plays an essential
      role in the catalytic mechanism of various proteins, including human glutamate
      oxaloacetate transaminase (hGOT1), an important enzyme in amino acid metabolism.
      A recent molecular and genetic study showed that the E266K, R267H, and P300L
      substitutions in aspartate aminotransferase, the Arabidopsis analog of hGOT1,
      genetically suppress a developmentally arrested Arabidopsis RUS mutant.
      Furthermore, CD analyses suggested that the variants exist as apo proteins and
      implicated a possible role of PLP in the regulation of PLP homeostasis and
      metabolic pathways. In this work, we assessed the stability of PLP bound to hGOT1
      for the three variant and wildtype (WT) proteins using a combined 6 MUs of
      molecular dynamics (MD) simulation. For the variants and WT in the holo form, the
      MD simulations reproduced the "closed-open" transition needed for substrate
      binding. This conformational transition was associated with the rearrangement of
      the P15-R32 small domain loop providing substrate access to the R387/R293 binding
      motif. We also showed that formation of the dimer interface is essential for PLP
      affinity to the active site. The position of PLP in the WT binding site was
      stabilized by a unique hydrogen bond network of the phosphate binding cup, which
      placed the cofactor for formation of the covalent Schiff base linkage with K259
      for catalysis. The amino acid substitutions at positions 266, 267, and 300
      reduced the structural correlation between PLP and the protein active site and/or
      integrity of the dimer interface. Principal component analysis and energy
      decomposition clearly suggested dimer misalignment and dissociation for the three
      variants tested in our work. The low affinity of PLP in the hGOT1 variants
      observed in our computational work provided structural rationale for the possible
      role of vitamin B6 in regulating metabolic pathways.

PMID- 30208108
TI  - Antigenic evolution of viruses in host populations.
AB  - To escape immune recognition in previously infected hosts, viruses evolve
      genetically in immunologically important regions. The host's immune system
      responds by generating new memory cells recognizing the mutated viral strains.
      Despite recent advances in data collection and analysis, it remains conceptually
      unclear how epidemiology, immune response, and evolutionary factors interact to
      produce the observed speed of evolution and the incidence of infection. Here we
      establish a general and simple relationship between long-term cross-immunity,
      genetic diversity, speed of evolution, and incidence. We develop an analytic
      method fusing the standard epidemiological susceptible-infected-recovered
      approach and the modern virus evolution theory. The model includes the factors of
      strain selection due to immune memory cells, random genetic drift, and clonal
      interference effects. We predict that the distribution of recovered individuals
      in memory serotypes creates a moving fitness landscape for the circulating
      strains which drives antigenic escape. The fitness slope (effective selection
      coefficient) is proportional to the reproductive number in the absence of
      immunity R0 and inversely proportional to the cross-immunity distance a, defined
      as the genetic distance of a virus strain from a previously infecting strain
      conferring 50% decrease in infection probability. Analysis predicts that the
      evolution rate increases linearly with the fitness slope and logarithmically with
      the genomic mutation rate and the host population size. Fitting our analytic
      model to data obtained for influenza A H3N2 and H1N1, we predict the annual
      infection incidence within a previously estimated range, (4-7)%, and the
      antigenic mutation rate of Ub = (5 - 8) ? 10-4 per transmission event per genome.
      Our prediction of the cross-immunity distance of a = (14 - 15) aminoacid
      substitutions agrees with independent data for equine influenza.

PMID- 30208109
TI  - Functional estimation of bony segment lengths using magneto-inertial sensing:
      Application to the humerus.
AB  - Inertial sensor technology has assumed an increasingly important role in the
      field of human motion analysis. However, the reliability of the kinematic
      estimates could still be critical for specific applications in the field of
      functional evaluation and motor rehabilitation. Within this context, the
      definition of subject-specific multi-body kinematic models is crucial since it
      affects the accuracy and repeatability of movement reconstruction. A key step for
      kinematic model calibration is the determination of bony segment lengths. This
      study proposes a functional approach for the in vivo estimation of the humerus
      length using a single magneto-inertial measurement unit (MIMU) positioned on the
      right distal posterior forearm. The humerus length was estimated as the distance
      between the shoulder elevation axis and the elbow flexion-extension axis. The
      calibration exercise involved five shoulder elevations in the sagittal plane with
      the elbow completely extended and five elbow flexion-extensions with the upper
      arm rigidly aligned to the trunk. Validation of the method was conducted on five
      healthy subjects using the humerus length computed from magnetic resonance
      imaging as the gold standard. The method showed mean absolute errors of 12 +/- 9
      mm, which were in the estimate of the humerus length. When using magneto-inertial
      technology, the proposed functional method represents a promising alternative to
      the regressive methods or manual measurements for performing kinematic model
      calibrations. Although the proposed methodology was validated for the estimation
      of the humerus length, the same approach can be potentially extended to other
      body segments.

PMID- 30208110
TI  - Association between proton pump inhibitor use and the risk of pancreatic cancer:
      A Korean nationwide cohort study.
AB  - PURPOSE: Proton pump inhibitor (PPI) therapy causes hypergastrinemia, which could
      promote the development and progression of pancreatic cancer. Accordingly, this
      study aimed to investigate the association between PPI exposure and the risk of
      pancreatic cancer. METHODS: We conducted a twelve-year longitudinal population
      based study (2002-2013) using the Korean National Health Insurance Corporation
      claims database merged with national health examination data. The study cohort
      included 453,655 cancer-free individuals in January 2007 (index date). Incident
      pancreatic cancer was assessed throughout follow up until December 2013. The
      exposure to PPIs before the index date was assessed using a standardized Defined
      Daily Dose (DDD) system. We calculated the hazard ratios (HRs) and their 95%
      confidence intervals (CIs) for pancreatic cancer risk associated with cumulative
      PPI use using Cox proportional hazard regression models. RESULTS: There were
      3,086 cases of pancreatic cancer during the period of 2,920,000 person-years. PPI
      users exceeding 60 DDDs were at a higher risk of pancreatic cancer compared with
      non-users (HR, 1.34; 95% CI, 1.04-1.72). Subgroup analyses revealed that a
      significant association existed between PPI use and pancreatic cancer in low risk
      groups including individuals who were female, engaged in healthy lifestyle
      habits, and had no history of diabetes or chronic pancreatitis. CONCLUSION:
      Exposure to PPI appears to increase the risk of pancreatic cancer, independent of
      conventional risk factors.

PMID- 30208111
TI  - Association between the detection of alcohol, illicit drugs and/or psychotropic
      medications/opioids in patients admitted due to trauma and trauma recidivism: A
      cohort study.
AB  - OBJECTIVE: To quantify the association between the presence and type of drug
      detected and trauma recidivism in a cohort of patients admitted due to trauma.
      METHOD: A cohort study was conducted based on data from a project where the
      presence of alcohol and other drugs (cannabis, cocaine, amphetamines,
      methamphetamines, tricyclic antidepressants, barbiturates, opiates and
      benzodiazepines) was analysed in 1,187 patients aged 16 to 70 years admitted due
      to trauma. The patients were followed for a period of between 10 to 52 months
      until June 2016. For this study, the recurrence of injuries from a sample of 929
      patients from this cohort was analysed according to their consumption profile.
      Survival curves were estimated and adjusted Hazard Rate Ratios (aHRR) and
      adjusted incidence rate ratios (aIRR) were calculated. RESULTS: The incidence
      rate of TR was 10.94 cases per 100 patient-years in the group of patients
      negative for substances and 27.99 per 100 patient-years in positive patients. The
      survival curves show very significant differences in cumulative recurrence-free
      survival between the groups (Log Rank: p<0.001). Both the aHRR and the aIRR
      estimates show an increased risk of re-injury due to alcohol consumption (aIRR:
      2.33 (1.72-3.15), p<0.001), cannabis use (aIRR: 1.87 (1.09-3.20), p = 0.022) and
      polydrug use (aIRR: 2.34 (1.80-3.04), p<0.001). CONCLUSIONS: The presence of
      alcohol and/or illicit drugs in these patients doubles the risk of trauma
      recidivism.

PMID- 30208112
TI  - Insights on a putative aminoacyl-tRNA-protein transferase of Leishmania major.
AB  - The N-end rule pathway leads to regulated proteolysis as an adaptive response to
      external stress and is ubiquitous from bacteria to mammals. In this study, we
      investigated a gene coding for a putative core enzyme of this post-translational
      regulatory pathway in Leishmania major, which may be crucial during
      cytodifferentiation and the environment adaptive responses of the parasite.
      Leucyl, phenylalanyl-tRNA protein transferase and arginyl-tRNA protein
      transferase are key components of this pathway in E. coli and eukaryotes,
      respectively. They catalyze the specific conjugation of leucine, phenylalanine or
      arginine to proteins containing exposed N-terminal amino acid residues, which are
      recognized by the machinery for the targeted proteolysis. Here, we characterized
      a conserved hypothetical protein coded by the LmjF.21.0725 gene in L. major. In
      silico analysis suggests that the LmjF.21.0725 protein is highly conserved among
      species of Leishmania and might belong to the Acyl CoA-N-acyltransferases (NAT)
      superfamily of proteins. Immunofluorescence cell imaging indicates that the
      cytosolic localization of the studied protein and the endogenous levels of the
      protein in promastigotes are barely detectable by western blotting assay. The
      knockout of the two alleles of LmjF.21.0725 by homologous recombination was only
      possible in the heterozygous transfectant expressing LmjF.21.0725 as a transgene
      from a plasmid. Moreover, the kinetics of loss of the plasmid in the absence of
      drug pressure suggests that maintenance of the gene is essential for promastigote
      survival. Here, evidence is provided that this putative aminoacyl tRNA-protein
      transferase is essential for parasite survival. The enzyme activity and
      corresponding post-translational regulatory pathway are yet to be investigated.

PMID- 30208114
TI  - Cardio-respiratory autonomic responses to nociceptive stimuli in patients with
      disorders of consciousness.
AB  - The autonomic response to pain might discriminate among consciousness disorders.
      Therefore, aim of this study was to describe differences between minimally
      conscious state (MCS) and unresponsive wakefulness syndrome (UWS) patients in
      their autonomic response to a nociceptive stimulus. ECG, respiration, finger
      blood pressure (BP) and total peripheral resistances (TPR) were continuously
      recorded before, during and after a standardized noxious stimulus in 20 adult
      brain-injured patients, 14 in UWS and 6 in MCS. Occurrence of fast autonomic
      responses synchronous with the stimulus was detected by visual inspection of the
      tracings; short-term (<20 s) and long-term (between 20s and 50 s from the
      stimulus) responses were evaluated by beat-by-beat quantitative analysis. The
      noxious stimulus elicited fast responses in both groups, but only MCS patients
      showed a significant short-term response in TPR and long-term response in HR.
      Thus, short- and long-term cardiovascular responses to pain might integrate neuro
      behavioural assessments to discriminate between MCS and UWS.

PMID- 30208115
TI  - Correction: Essential role of Plasmodium perforin-like protein 4 in ookinete
      midgut passage.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0201651.].

PMID- 30208113
TI  - Prolonging culture of primary human keratinocytes isolated from suction blisters
      with the Rho kinase inhibitor Y-27632.
AB  - Keratinocytes are the most abundant cell type in the epidermis. They prevent
      desiccation and provide immunological and barrier defense against potential
      pathogens such as Staphylococcus aureus and Candida albicans. The study of this
      first line of immune defense may be hindered by invasive isolation methods and/or
      improper culture conditions to support stem cell maintenance and other potential
      mechanisms contributing to long-term subcultivation in vitro. Primary
      keratinocytes have been successfully isolated from blister roofs induced by
      negative pressure, which separates the epidermis from the dermis in vivo in human
      subjects. This method allows collection of pure epidermal cells without dermal
      contamination in a minimally invasive manner. However, the isolated keratinocytes
      differentiate and senesce when cultured in vitro beyond five passages. Here, we
      present evidence that the Rho kinase (ROCK) inhibitor Y-27632 can be used to
      effectively increase the proliferative capabilities of keratinocytes isolated
      using the suction blister method, similar to what has been previously reported
      for primary keratinocytes isolated using alternative methods. We show that the
      increase in passage number is directly correlated to delayed differentiation, and
      that cells passaged long term with the inhibitor retain their ability to stratify
      in organotypic raft cultures and respond to cytokine treatment; additionally, the
      late passage cells have a heterogeneous mix of differentiated and non
      differentiated cells which may be predicted by a ratio of select differentiation
      markers. The described method presents a minimally invasive procedure for
      keratinocyte isolation and prolonged culture that allows analysis of keratinocyte
      function in both healthy volunteers and patients with dermatologic diseases.

PMID- 30208116
TI  - Effect of joint mimicking loading system on zonal organization into tissue
      engineered cartilage.
AB  - Cartilage tissue engineering typically involves the combination of a
      biodegradable polymeric support material with chondrocytes. The culture
      environment in which cell-material constructs are created and stored is an
      important factor. The aim of the present study was to investigate the effects of
      combined stimuli on cartilage zonal organization which is important to maintain
      cartilage functions such as lubrication and cushion. For that purpose, we
      developed a joint mimicking loading system which was composed of compression and
      shear stress. To mimic the joint loading condition, we manufactured a stimuli
      system that has a device similar to the shape of a femoral condyle in human knee.
      The fibrin/hyaluronic acid mixture with chondrocytes were dropped into support
      made of silicon, and placed under the device. The cartilage explants were
      stimulated with the joint mimicking loading system for 1 hour per day over the
      course of 4 weeks. The amounts of GAG and collagen in the stimulated tissue were
      more than that of the static cultured tissue. Cells and collagen were arranged
      horizontally paralleled to the surface by stimuli, while it did not happen in the
      control group. The results of this study suggests that mechanical load exerting
      in the joint play a crucial role in stimulation of extracellular matrix (ECM)
      production as well as its functional rearrangement.

PMID- 30208117
TI  - Adding insult to injury: Ship groundings are associated with coral disease in a
      pristine reef.
AB  - In 2013, the remote Tubbataha Reef UNESCO World Heritage Site, in the western
      Philippines, experienced two ship groundings within four months: the USS Guardian
      (USSG), a US military vessel, and the Min Ping Yu (MPY), an illegal Chinese
      fishing vessel. Here, we present the results of coral disease assessments
      completed two years post-grounding and recovery patterns monitored annually
      within these grounding sites. Site assessments were undertaken in three distinct
      zones: 'ground zero', where reef was scoured to its limestone base by direct ship
      impact; the 'impact border', containing surviving upright but damaged, abraded
      and fragmented colonies injured during ship movement; and undamaged 'control'
      sites, remote from the ship groundings but located on the same atoll. Coral
      diseases were dominated by white syndromes, and prevalence was an order of
      magnitude higher within the impact border zones than within the other zones two
      years after the events. Hard coral cover has steadily increased at a mean rate of
      3% per year within the scoured USSG site at a rate comparable to control sites.
      In contrast, recovery has been negligible within the rubble-dominated MPY site,
      suggesting that substrate quality strongly influenced recovery processes such as
      recruitment, as larvae do not survive well on unstable substrates. Long-term
      recovery trajectories from these two grounding events appeared strongly
      influenced by movement of the ship during and after each event, and site-specific
      wave-influenced persistence of rubble and debris. High prevalence of coral
      disease among damaged but surviving colonies two years post-grounding suggested
      long-term impacts which may be slowing recovery and creating localized pockets of
      higher persistent disease prevalence than that of the surrounding population.

PMID- 30208118
TI  - Consideration of future consequences (CFC) serves as a buffer against aggression
      related to psychopathy.
AB  - Psychopathy is the most notorious trait in the Dark Triad, and it is strongly
      linked to many kinds of aggressive behaviors. However, not every individual who
      is characterized by psychopathy engages in aggression, which suggests that
      certain factors may attenuate the intensity of the relations between psychopathy
      and aggression. The purpose of the current study was to explore the protective
      roles of the consideration of future consequences (CFC) (high CFC-Future and low
      CFC- Immediate) in attenuating aggression related to psychopathy using proactive
      aggression (Study 1) and cyber-aggression (Study 2) behavior indexes. College
      students (Study 1; N = 1,058) and adults (Study 2; N = 350) voluntarily
      participated in this study. The results demonstrated that the relationship
      between psychopathy and aggressive behaviors was moderated by CFC-Future and CFC
      Immediate. Individuals with high psychopathy scores who also had high CFC-Future
      scores or low CFC-Immediate scores exhibited less proactive aggression (Study 1)
      and left fewer aggressive online comments on news websites (Study 2). The results
      of the present study suggested that CFC serves as a buffer against aggression
      related to psychopathy and may extend the knowledge of the relationship between
      psychopathy and aggression.

PMID- 30208119
TI  - Identification of MMP28 as a biomarker for the differential diagnosis of
      idiopathic pulmonary fibrosis.
AB  - BACKGROUND AND OBJECTIVE: Idiopathic Pulmonary Fibrosis (IPF) is a progressive
      disease of unknown etiology. The diagnosis is based on the identification of a
      pattern of usual interstitial pneumonia either by high resolution computed
      tomography and/or histology. However, a similar pattern can be observed in other
      fibrotic lung disorders, and precise diagnosis remains challenging. Studies on
      biomarkers contributing to the differential diagnosis are scanty, and still in an
      exploratory phase. Our aim was to evaluate matrix metalloproteinase (MMP)-28,
      which has been implicated in abnormal wound healing, as a biomarker for
      distinguishing IPF from fibrotic non-IPF patients. METHODS: The cell localization
      of MMP28 in lungs was examined by immunohistochemistry and its serum
      concentration was measured by ELISA in two different populations. The derivation
      cohort included 82 IPF and 69 fibrotic non-IPF patients. The validation cohort
      involved 42 IPF and 41 fibrotic non-IPF patients. RESULTS: MMP28 was detected
      mainly in IPF lungs and localized in epithelial cells. In both cohorts, serum
      concentrations of MMP28 were significantly higher in IPF versus non-IPF (mostly
      with lung fibrosis associated to autoimmune diseases and chronic hypersensitivity
      pneumonitis) and healthy controls (ANOVA, p<0.0001). The AUC of the derivation
      cohort was 0.718 (95%CI, 0.635-0.800). With a cutoff point of 4.5 ng/mL, OR was
      5.32 (95%CI, 2.55-11.46), and sensitivity and specificity of 70.9% and 69%
      respectively. The AUC of the validation cohort was 0.690 (95%CI, 0.581-0.798), OR
      4.57 (95%CI, 1.76-12.04), and sensitivity and specificity of 69.6% and 66.7%.
      Interestingly, we found that IPF patients with definite UIP pattern on HRCT
      showed higher serum concentrations of MMP28 than non-IPF patients with the same
      pattern (7.8+/-4.4 versus 4.9+/-4.4; p = 0.04). By contrast, no differences were
      observed when IPF with possible UIP-pattern were compared (4.7+/-3.2 versus 3.9+/
      3.0; p = 0.43). CONCLUSION: These findings indicate that MMP28 might be a useful
      biomarker to improve the diagnostic certainty of IPF.

PMID- 30208124
TI  - Gastrointestinal and ectoparasites of plumbeous rail, Pardirallus sanguinolentus
      (Aves: Rallidae) in Central Chile.
AB  - With the aim to identify the parasite fauna of plumbeous rail, Pardirallus
      sanguinolentus (Aves: Rallidae) in Chile, 26 carcasses were parasitologically
      necropsied. The present study revealed the presence of 14 species of parasites
      (inverse Simpson index = 4.64; evenness = 0.332), including ectoparasites:
      feather mites: Analloptes megnini , Grallobia sp., Grallolichus sp., Megniniella
      sp., and Metanalges sp.; the feather lice Pseudomenopon meinertzhageni, Rallicola
      andinus, and Fulicoffula sp.; and six species of gastrointestinal helminths:
      Heterakis psophiae, Porrocaecum ardeae, Tetrameres sp., Capillaria sp., Diorchis
      sp., and Plagiorhynchus sp. The relatively high parasite richness that was found
      could be attributed to the highly favorable conditions of wetlands for parasite
      development. All parasites found, except feather lice, are new records for
      plumbeous rail. A checklist of parasites for plumbeous rail is presented.

PMID- 30208125
TI  - Toxoplasma gondii: infection among shelter and stray cats in Rio de Janeiro,
      Brazil.
AB  - The aim of this study was to identify possible infection of Toxoplasma gondii
      among cats in a shelter and a set of condominiums in the city of Rio de Janeiro,
      through changes to the cats' serological status between two different times in
      2014 and 2015. One group was made up of captive cats at the municipal shelter and
      the other comprised stray cats that circulated in condominiums in the city. On
      the first occasion, cats were caught and tagged through application of
      microchips; in this manner, blood samples were obtained from 261 captive cats and
      172 stray cats. On the second occasion, blood samples were obtained from 94
      captive cats and 56 recaptured stray cats. The serological diagnosis was made by
      means of the indirect hemagglutination assay (IHA) and indirect
      immunofluorescence reaction (IFAT) (cutoff >= 64). The frequency of T. gondii
      infection among the captive cats was 24.5% and among the stray cats, 18%. With
      the second analysis, it was possible to verify modifications to the serological
      status of anti-T. gondii antibodies, in 18% of both populations of animals. The
      presence of seroconversion shows that infection was possibly occurring in the
      region at the time of the study.

PMID- 30208126
TI  - Fashion braces: an alarming trend.

PMID- 30208127
TI  - Morphological and immunohistochemical analysis of proteins CASPASE 3 and XIAP in
      rats subjected to cerebral ischemia and chronic alcoholism.
AB  - PURPOSE: To evaluate histopathological and ultrastructural changes and expression
      of proteins related to apoptosis CASPASE 3 and XIAP after experimental induction
      of temporary focal cerebral ischemia (90 minutes) due to obstruction of the
      middle cerebral artery in alcoholism model. METHODS: Forty adult Wistar rats were
      used, subdivided into 5 experimental groups: control group (C); Sham group (S);
      Ischemic group (I); Alcoholic group (A); and Ischemic and Alcoholized group
      (I+A): animals submitted to the same treatment of group A and after four weeks
      were submitted to focal cerebral ischemia during 90 minutes, followed by
      reperfusion of 48 hours. Were processed for histopathological analysis and
      immunohistochemistry (for the protein expression of CASPASE -3 and XIAP).
      RESULTS: Greater histopathological changes were observed in the animals of groups
      I and I+A in the three areas analyzed. The neuronal loss was higher in the medial
      striatum region of the animals of groups I and I + A. The protein expression of
      CASPASE -3 was higher than that of XIAP in the groups I and I + A for both
      proteins. CONCLUSION: The expression of XIAP was slightly higher where the
      histopathological changes and expression of CASPASE -3 was less evident.

PMID- 30208128
TI  - Correlations of inhaled NO with the cTnI levels and the plasma clotting factor in
      rabbits with acute massive pulmonary embolism.
AB  - PURPOSE: To investigate the correlation of inhaled nitric oxide (NO) on plasma
      levels of cardiac troponin I (cTnI) and von Willebrand factor (vWF), glycoprotein
      (GP) IIb/IIIa, granule membrane protein 140 (GMP-140) in rabbits with acute
      massive pulmonary embolism (PE). METHODS: Thirty apanese white rabbits were
      divided into 3 groups, thrombus were injected in model group (n = 10), NO were
      inhalated for 24 h after massive PE in NO group (n = 10), saline were injected in
      control group (n = 10). The concentrations of vWF, GP IIb/IIIa, GMP-140 and cTnI
      were tested at 4, 8, 12, 16, 20, and 24 h, Correlation analyses were conducted
      between cTnI and vWF, GP IIb/IIIa, and GMP-140 by Pearson's correlation. RESULTS:
      The concentration of cTnI and vWF, GP IIb/IIIa, and GMP-140 was increased in the
      model group, compared to control group. In the inhaled group, the concentrations
      of cTnI, vWF, GP IIb/IIIa, and GMP-140 were reduced compared to model group.
      There was a positive correlation between cTnI and vWF, GP IIb/IIIa, and GMP-140.
      CONCLUSION: Inhaled nitric oxide can lead to a decrease in levels of cardiac
      troponin I, von Willebrand factor, glycoprotein, and granule membrane protein
      140, after an established myocardial damage, provoked by acute massive pulmonary
      embolism.

PMID- 30208129
TI  - Bacterial cellulose to reinforce urethrovesical anastomosis. A translational
      study.
AB  - PURPOSE: To evaluate the efficacy of the cellulosic exopolysaccharide membrane
      (CEM) as a urethral reinforcement for urethrovesical anastomosis. METHODS: Twenty
      eight rabbits were submitted to urethrovesical anastomosis with or without CEM
      reinforcement. The animals were divided into 4 groups: C7, CEM7, C14 and CEM14:
      (C= only anastomosis or CEM = anastomosis + CEM), evaluated after 7 weeks, and 14
      weeks. The biointegration and biocompatibility of CEM were evaluated according to
      stenosis, fistula, urethral wall thickness, urethral epithelium, rate of
      inflammation and vascularization. RESULTS: Between the two experimental groups,
      the difference in the number of stenosis or urinary fistula was not statistically
      significant. The morphometric analysis revealed preservation of urethral lumen,
      well adhered CEM without extrusion, a controlled inflammatory process and implant
      vascularization. The urothelium height remained constant over time after CEM
      reinforcement and the membrane wall was thicker, statistically, after 14 weeks.
      CONCLUSION: The absence of extrusion, stenosis or urinary fistula after 14 weeks
      of urethrovesical anastomosis demonstrates cellulosic exopolysaccharide membrane
      biocompatibility and biointegration with tendency to a thicker wall.

PMID- 30208130
TI  - Prospective clinical assessment of tibial tuberosity advancement for the
      treatment of cranial cruciate ligament rupture in dogs.
AB  - PURPOSE: To evaluate clinically dogs that underwent tibial tuberosity advancement
      (TTA) six months previously. METHODS: Dogs of various breeds, gender, weight, and
      age that had CCL rupture and underwent TTA for treatment were included in this
      study. Parapatellar arthrotomy was performed in all patients to assess the joint
      for a ruptured ligament and meniscal injury before the TTA. The appropriate cage
      for the TTA was chosen with planning surgery. The surgical procedure was
      performed according to the literature, using a modified Maquet technique. Six
      months after surgery, lameness during walking; muscular atrophy; crepitation,
      cranial drawer and tibial compression tests and quality of life based on owner's
      evaluation were assessed. RESULTS: Postoperative complications were observed in
      only one knee (4.76%), with a surgical site seroma. The mean lameness score at
      walking was 0.29 (+/- 0.64). The mean score regarding muscular atrophy was 0.95
      (+/- 1.56). The mean score of the cranial drawer test, in a range from 0 to 5,
      was 1.52 (+/- 1.54). The owners rated the dog's quality of life as excellent in
      44%, good in 30%, and moderate in 17%. CONCLUSION: This clinical study supports
      the affirmation that patients who undergo TTA for treatment of CCL rupture have
      an acceptable response.

PMID- 30208131
TI  - Comparative safety assessments of the biosimilar APZ001 and Erbitux in pre
      clinical animal models.
AB  - PURPOSE: To evaluate the toxicity of Erbitux as well as its biosimilar APZ001
      antibody (APZ001) in pre-clinical animal models including mice, rabbits and
      cynomolgus monkeys. METHODS: We performed analysis of normal behavior activity,
      autonomic and non-autonomic nervous functions, nervous-muscle functions, nervous
      excitability and sensorimotor functions on CD-1 mice. Subsequently, we studied
      that effects of APZ001 and Erbitux on respiratory system, cardiovascular system
      and kidney in Cynomolgus monkey models and performed local tolerance experiments
      on New Zealand rabbits. RESULTS: The comparisons between APZ001 and Erbitux
      showed no significant differences in mice autonomic nervous system, nervous
      muscle functions, non-autonomic nervous functions, nervous excitability and
      sensorimotor functions between treated and untreated group (p>0.05). APZ001 and
      Erbitux showed negative effect on CD-1 mice in the present of pentobarbital
      sodium anesthesia (p>0.05). Single administrations of high, medium or low doses
      of APZ001 did not lead to monkey urine volume alterations (p>0.05). In human
      tissues, APZ001 and Erbitux showed positive signals in endocardium, lung type II
      alveolar epithelial cell and surrounding vessels, but showed negative results in
      kidney and liver tissues. No hemolysis phenomenon and serious side-effects in
      vessels and muscles were observed in rabbits when administrated with APZ001 and
      Erbitux respectively. CONCLUSION: The safety comparisons between APZ001 antibody
      and Erbitux showed that these two antibodies showed highly similarities in mice,
      rabbits and cynomolgus monkey animal models in consideration of pharmaceutical
      effects, indicating APZ001 might be a suitable substitute for Erbitux.

PMID- 30208132
TI  - The role of vitamin C in the gene expression of oxidative stress markers in
      fibroblasts from burn patients.
AB  - PURPOSE: To assess the action of vitamin C on the expression of 84 oxidative
      stress related-genes in cultured skin fibroblasts from burn patients. METHODS:
      Skin samples were obtained from ten burn patients. Human primary fibroblasts were
      isolated and cultured to be distributed into 2 groups: TF (n = 10, fibroblasts
      treated with vitamin C) and UF (n = 10, untreated fibroblasts). Gene expression
      analysis using quantitative polymerase chain reaction array was performed for
      comparisons between groups. RESULTS: The comparison revealed 10 upregulated genes
      as follows: arachidonate 12-lipoxygenase (ALOX12), 24-dehydrocholesterol
      reductase (DHCR24), dual oxidase 1 (DUOX1), glutathione peroxidase 2 (GPX2),
      glutathione peroxidase 5 (GPX5), microsomal glutathione S-transferase 3 (MGST3),
      peroxiredoxin 4 (PRDX4), phosphatidylinositol-3,4,5-trisphosphate dependent Rac
      exchange factor 1 (P-REX1), prostaglandin-endoperoxide synthase 1 (PTGS1), and
      ring finger protein 7 (RNF7). CONCLUSION: Cultured fibroblasts obtained from burn
      patients and treated with vitamin C resulted in 10 differentially expressed
      genes, all overexpressed, with DUOX1, GPX5, GPX2 and PTGS1 being of most
      interest.

PMID- 30208133
TI  - Simulated training of a laparoscopic vesicourethral anastomosis.
AB  - PURPOSE: To develop a model and curriculum for simulated training of an effective
      and well accepted laparoscopic vesicourethral anastomosis (VUA). METHODS:
      Experimental longitudinal study of quantitative character. The sample consisted
      of 12 general surgery residents and 6 urology residents (R3). The training
      consisted of making twelve VUAs on synthetic organs. The training was divided
      into four sessions and accompanied by an instructor who performed positive
      feedback. The evaluation of the anastomoses considered the time and the analysis
      of the operative technique through the global evaluation scale Objective
      Structured Assessment of Technical Skills (OSATS). RESULTS: Residents showed a
      reduction in operative time and evolution in the surgical technique statistically
      significant (p<0.01). The best-rated items were the facilitator positive feedback
      and the fact that the training was carried out at the teaching hospital premises.
      CONCLUSIONS: The proposed training model was well accepted and proved to be
      effective in reducing operative time and improving laparoscopic skills. The
      training should be fractionated (4 sessions in 3 weeks), repetitive (12
      anastomoses) and have positive feedback.

PMID- 30208134
TI  - Liver ischemia and reperfusion injury. Pathophysiology and new horizons in
      preconditioning and therapy.
AB  - It is well known that during hepatic operative procedures, it is often critical
      that the irrigation is interrupted to avoid possible bleeding, blood
      transfusions, variable intensities, and their short and long-term consequences.
      It was believed in the past that the flow interruption should not exceed 20
      minutes, which limited the use of this maneuver. However, it has been postulated
      that ischemia could be maintained for more than 60 minutes in healthy livers. The
      present paper review includes: 1) A brief introduction to justify the rationale
      of the review design; 2) Aspects of the pathophysiology of the three stages of
      the liver ischemia-reperfusion injury; 3) The innate and acquired immunity; 4)
      Oxidative stress; 5) Apoptosis and autophagy, Some essential biomarkers (Tumor
      Necrosis Factor-alpha, nitric oxide, metalloproteinases); and, finally; 6)
      Preventive ("cheating") strategies, non-pharmacological and pharmacological
      options to treat the liver IR injury.

PMID- 30208135
TI  - The number of citations in a scientific journal does not increase through an
      administrative act.

PMID- 30208136
TI  - The effect of smoking cessation on posterior ocular structures.
AB  - PURPOSE: This study evaluated changes in cho-roidal and macular thickness in
      healthy volunteers and chronic smokers. METHODS: Thirty-three eyes of 33 chronic
      smokers (study group) and 33 eyes of 33 healthy controls who had never smoked
      were prospectively evaluated. Comprehensive ophthalmic assessment included slit
      lamp biomicroscopy, stereoscopic fundus examination, and intraocular pressure
      measurement. Spectral domain optical coherence tomography was used to measure
      choroidal and macular thickness 1 month before smoking cessation (smoking period)
      and after 3 months of smoking cessation (nonsmoking period). RESULTS: The mean
      age of the participants was 41.88 +/- 6.52 years (range, 26-52), and the average
      smoking duration was 8.6 +/- 2.5 years (range, 5-16). The thickness of the
      paracentral choroid (nasal: 1,500 mm, p=0.001 and temporal: 1,500 mm, p=0.001)
      had significantly decreased after 3 months of smoking cessation. The thicknesses
      of the subfoveal choroid in the smoking and nonsmoking periods were not
      significantly different (p=0.194). The mean central macular thickness was 267.21
      +/- 18.42 mm in the smoking period and 268.42 +/- 18.28 mm in the nonsmoking
      period (p=0.022). CONCLUSIONS: Smoking was associated with statistically
      significant changes in paracentral choroidal and central macular thickness in
      healthy volunteers. Pathological studies should be performed to evaluate the
      effects of smoking on posterior ocular structures.

PMID- 30208137
TI  - Dermis-fat graft for anophthalmic socket reconstruction: indications and
      outcomes.
AB  - PURPOSE: To evaluate the outcomes of dermis-fat graft procedure for orbital
      volume replacement in anophthalmic socket. METHODS: A retrospective chart review
      was performed studying all dermis-fat graft surgeries done at King Khlaed Eye
      Specialist Hospital in the last 10-year period. Sixty-two anophthalmic socket
      carriers underwent dermis-fat graft during the study period. Data were collected
      on characteristics of the patients, postoperative complications, cosmesis, and
      functional results such as the ability to hold an external prosthesis. RESULTS:
      Mean age of the patients included in the study was 34.2 +/- 9.7 years. There were
      38.7% of patients with grade 3 anophthalmic socket, 64.5% of patients had an
      acquired anophthalmic socket, and dermis-fat graft was performed as a secondary
      procedure in 61.3% of patients. Postoperative complications included
      lagophthalmos (22.6%), graft necrosis (17.7%), pyogenic granuloma (12.9%),
      decreased graft size (12.9%), malpositioned lids (3.2%), and volume deficiency
      (3.2%). The prosthesis was held in place in 49 patients (79%) preoperatively and
      in 55 patients (88.7%) postoperatively. CONCLUSION: Dermis-fat graft is an
      excellent option for congenital or acquired as well as primary or secondary
      anophthalmic sockets, with or without contraction. The outcomes are favorable,
      and complications are rare.

PMID- 30208138
TI  - Microbiological analysis of contact lens cases: impact of the hospital
      environment.
AB  - PURPOSE: The aim of this study was to analyze the bacterial and fungal microbiota
      found in contact lens cases among two groups of patients to correlate the data on
      the habits of contact lens users and to evaluate whether there is a difference in
      the culture results between users of ridged and nonridged contact lens cases.
      METHODS: Two groups (35 patients per group) were included, consisting of hospital
      workers and those who had not visited a hospital in the past 30 days, and a
      questionnaire regarding epidemiological data and habits related to contact lens
      and lens case use was administered. In addition, 140 samples collected from the
      right and left compartments of each lens case by swabbing the bottom of the wells
      were tested using bacterioscopy as well as fungal and bacterial cultures via
      computerized identification of the species. RESULTS: No fungal growth was
      identified in any of the 70 contact lens cases; however, bacteria were found in
      39 cases, and there was no statistical difference between the groups. Most
      bacteria (>85%) were gram-negative bacilli. Contamination inone compartment of
      the contact lens case elevated the risk of contamination of the other side
      (>80%). Moreover, contamination was statistically higher in the ridged cases than
      in nonridged cases (p=0.0149). CONCLUSION: The types of bacteria contaminating
      the cases are generally not seen in eye diseases associated with contact lens
      use, suggesting that other decisive variables are involved in eye infection from
      a contaminated lens or case. Fungal contamination of contact lens cases appears
      to be an exception. Ridged cases are commonly used by contact lens wearers and
      present a potential risk to eye health. In addition, the results of bacterial
      tests between hospital workers and those who did not visit a hospital were not
      significantly different.

PMID- 30208139
TI  - Induction of pluripotent stem cells by reprogramming human ocular fibroblasts
      under xeno-free conditions.
AB  - PURPOSES: To develop an efficient and xeno-free standard eye-derived induced
      pluripotent stem cell reprogramming protocol for use during induced pluripotent
      stem cell-based cell therapies in treating retinal degenerative diseases and to
      compare the relative effectiveness of both animal- and non-animal-derived culture
      systems in the generation of induced pluripotent stem cells. METHODS: Primary
      cultured human pterygium fibroblasts and human Tenon's capsule fibroblasts were
      induced to induced pluripotent stem cells using a non-in-tegrated virus under two
      xeno-free systems; as part of this study, a traditional non-xeno-free
      reprogramming system was also assessed. Induced pluripotent stem cell clones were
      selected and counted by live staining. Reprogramming efficiencies were evaluated
      between the fibroblasts and among different culture systems. In a series of
      experiments, such as PCR and immunofluorescence staining, the induced pluripotent
      stem cells were characterized. RESULTS: Human pterygium fibroblast- and human
      Tenon's capsule fibroblast-derived induced pluripotent stem cells were
      successfully established using different reprogramming systems, under which they
      exhibited properties of induced pluripotent stem cells. Reprogramming
      efficiencies of induced pluripotent stem cells using the cell therapy system, the
      traditional system, and the E6/E8 system were 0.014%, 0.028%, and 0.001%,
      respectively, and those of human pterygium fibroblast- and human Tenon's capsule
      fibroblast-derived induced pluripotent stem cells-using the aforementioned
      systems-were 0.018% and 0.017%, respectively. CONCLUSIONS: Sendai virus
      facilitates induced pluripotent stem cell reprogramming of ocular fibroblasts
      both human pterygium and human Tenon's capsule fibroblasts being safe and
      efficient for induced pluripotent stem cell reprogramming. Although the
      reprogramming efficiencies of ocular-derived induced pluripotent stem cells under
      xeno-free conditions were not superior to those observed using the traditional
      reprogramming system, the cell therapy system reprogramming system is a good
      option when induced pluripotent stem cells are to be induced under xeno-free
      conditions.

PMID- 30208140
TI  - Clinical features and corneal optical anisotropies in a rabbit model of limbal
      stem cell deficiency.
AB  - PURPOSES: To investigate the intra-laboratory reproducibility of clinical
      features and to evaluate corneal optical anisotropies in a rabbit model of limbal
      stem cell deficiency. METHODS: Limbal injury was induced in the right eye of 23
      adult New Zealand White rabbits using a highly aggressive protocol that combined
      360 degrees limbal peritomy, keratolimbectomy, alkaline chemical burn, and
      mechanical removal of the epithelium. Clinical evaluation of the injured eyes was
      performed for 28 days and included corneal impression cytology. Corneas with a
      severe clinical outcome set typical of limbal stem cell deficiency were then
      collected, subjected to a histopathological examination, and examined for optical
      anisotropies. Corneas from healthy rabbit eyes were used as controls. Differences
      in optical path due to stromal collagen birefringence, as well as linear
      dichroism related to the expression and spatial orientation of glycosaminoglycan
      chains from proteoglycans, were measured from cross-sections under a quantitative
      polarized light microscope. RESULTS: One eye showed signs of hypopyon and was
      excluded. Signs of ocular inflammation were observed in all eyes studied (n=22).
      Corneal impression cytology did not detect goblet cells. Twelve of the 22 corneas
      presented a clinical outcome set typical of limbal stem cell deficiency, which is
      characterized by the presence of epithelial defects, inflammatory cells, moderate
      to-severe opacity, and neovascularization. Microscopic studies under polarized
      light revealed that relative to controls, limbal stem cell deficiency caused a
      24.4% increase in corneal optical path differences. Further, corneas with limbal
      stem cell deficiency were less dichroic than controls. CONCLUSIONS: These results
      suggest that rabbit models of limbal stem cell deficiency must be rigorously
      screened for use in preclinical studies to ensure experimental homogeneity
      because protocols used to create limbal stem cell deficiency could be not
      associated with good intra-laboratory reproducibility of clinical features.
      Limbal stem cell deficiency, as induced herein, altered the optical anisotropic
      properties of the corneal stroma. Such alterations are indicative of changes in
      collagen packing and the spatial orientation of glycosaminoglycan chains from
      proteoglycans. Knowledge of these changes is important to potentiate strategies
      aimed at restoring the morphofunctional integrity of the corneal stroma affected
      by limbal stem cell deficiency.

PMID- 30208141
TI  - Thickness and immunohistochemistry of LASIK flaps created by different
      femtosecond lasers in eye-bank corneas.
AB  - PURPOSE: The aim of this study was to compare the corneal cell viability and
      thickness of LASIK flaps created by 3 femtosecond lasers in eye-bank human
      corneas. METHODS: Forty-five eye-bank human sclerocorneal buttons (15 corneas in
      each group) were examined after the creation of 120 mm-thick laser-assisted
      keratomileusis (LASIK) flaps with 150kHz iFS In-traLaseTM (IL), Z6 Femto LDVTM
      (LDV), or 200kHz WavelightTM FS200 (FS200). The thickness of the flaps was
      measured using anterior segment optical coherence tomography (AS-OCT; VisanteTM).
      Cell viability was blindly evaluated with immunohistochemistry for keratocyte
      apoptosis using anti-caspase 3 antibodies. RESULTS: The standard deviation from
      the intended flap thickness was less than 10 mm in all the groups. There was a
      statistically significant difference in corneas treated with LDV and IL with
      regard to the flap thickness horizontally at +3.00 mm (p=0.0124), -0.5 mm
      (p=0.0082), and -1.00 mm (p=0.0425) from the corneal vertex and +0.5 mm from the
      flap edge (p=0.0240), and those treated with LDV and FS200 with regard to the
      flap thickness horizontally at -0.5 mm from the corneal vertex (p=0.0082). The
      mean keratocyte apoptosis numbers were 13.09 +/- 1.10, 15.59 +/- 3.28, and 17.72
      +/- 1.49 in corneas treated with IL, FS200, and LDV, respectively (p<0.001).
      CONCLUSION: All 3 assessed femtosecond lasers provided predictable LASIK flap
      thickness. The mean stromal keratocyte apoptosis number was low in all groups.

PMID- 30208142
TI  - Eccentric fixation patterns, clinical findings, and reading speed in patients
      with bilateral toxoplasmic macular retinochoroiditis.
AB  - PURPOSE: To study visual acuity, refractive errors, eccentric fixation, and
      reading performance in patients with toxoplasmic macular retinochoroiditis.
      METHODS: Twenty-three participants with bilateral toxoplasmic macular
      retinochoroiditis and 4 with toxoplasmic macular retinocho-roiditis in their
      unique eye were evaluated. Participants reported their eye dominance, confirmed
      by the Portus and Miles test. Best corrected visual acuity, spherical equivalent
      refraction, magnification need, and reading speed were measured. Microperimetry
      (MAIA, Centervue - Padova, Italy) recorded the preferred retinal locus and
      fixation stability by means of the bivariate contour ellipse area. Fourteen eyes
      from 14 normally sighted subjects served as controls. RESULTS: Mean +/- SD best
      corrected visual acuity was better in the dominant eye than in the nondominant
      eye: 0.9 +/- 0.2 (logMAR 0.5 to 1.4) vs. 1.2 +/- 0.3 (logMAR 0.6 to 1.7)
      (p<0.0001, paired t-test). Spherical equivalent myopia of -4.00 or higher was
      present in 42% of the eyes. Microperimetry was performed in 42 eyes. Eccentric
      fixation was observed in all examined eyes. In 14 eyes (33%), the preferred
      retinal locus was placed (in the retina) superior temporal to the macular lesion,
      in 10 (24%) superior nasal, in 6 (14%) inferior temporal, and in 12 (28%)
      inferior nasal. There was no significant difference in the distribution of the
      preferred retinal locus position between dominant and nondominant eyes (p=0.85,
      Pearson test). There was no correlation between reading speed and the distance
      between the preferred retinal locus and the estimated original foveal position
      (r=-0.09; p=0.73), the bivariate contour ellipse area (r=-0.19; p=0.44), or best
      corrected visual acuity (r=0.024; p=0.92). CONCLUSIONS: Myopia is more prevalent
      in patients with toxoplasmic macular retinochoroiditis. Reading speed is not
      dependent on preferred retinal locus position, stability, or visual acuity.
      Nevertheless, documentation of fixation provides new data on the impact of visual
      impairment in these patients and may be useful for rehabilitation efforts.

PMID- 30208143
TI  - Retinal changes in rabbit after intravitreal injection of sunitinib encapsulated
      into solid lipid nanoparticles and polymeric nanocapsules.
AB  - PURPOSE: We aimed to evaluate the safety of single intravitreal injection of each
      of two concentrations of 0.1 ml of sunitinib (1 and 10 mg/ml), 0.1 ml of a drug
      free dispersion containing solid lipid nanoparticles, and 0.1 ml of a drug-free
      dispersion containing polymeric nanocapsules for analyzing the possible toxic
      effects using electrophysiology and histology in albino rabbit retina. METHODS:
      We conducted an experimental controlled study of 20 eyes of albino rabbits.
      Intravitreal injections of each specific agent were applied to one eye per rabbit
      in each 5-rabbit group, while the contralateral eyes received no treatment and
      were used as controls. RESULTS: We noted no electroretinographic changes in the
      sunitinib (1 and 10 mg/ml) or in solid lipid nanoparticles groups. However, we
      observed significant abnormalities in ocular morphology and in the
      electroretinogram in the nanocapsules group. At the histological level, only the
      nanocapsules group demonstrated abnormal changes, including severe edema and
      cytoplasmic vacuole formation. CONCLUSIONS: While nanocapsules intravitreal
      injections indicated retinal toxic effects, sunitinib and solid lipid
      nanoparticles intravitreal injections were not toxic to the retina. Our results
      suggest that a sunitinib preparation with solid lipid nanoparticles for
      controlled release may offer a significant therapeutic approach for
      vasoproliferative ocular disease.

PMID- 30208144
TI  - Magnitude of visual impairment, blindness and causes in the southwest region of
      Sao Paulo state, Brazil.
AB  - PURPOSES: The purpose of this study was to evaluate the magnitude and
      determinants of bilateral blindness and visual impairment (VI) in the southwest
      region of Sao Paulo State, Brazil. METHODS: This cross-sectional study conducted
      during 2013 and 2014 targeted people of all ages in 10 districts in the southwest
      region of Sao Paulo State, Brazil. Ophthalmologists in a mobile unit measured
      visual acuity and examined eyes. Visual acuity was categorized according to the
      World Health Organization sex-adjusted rates with 95% confidence intervals (CI)
      were calculated. Number of blindness and visually impaired was projected for the
      entire study area. RESULTS: We examined 2,306 participants. The age- and sex
      adjusted frequency of bilateral blindness was 0.26% (95% CI: 0.1-0.4). Females
      (0.35%) and patients 350 years old (0.58%) had higher rate of blindness compared
      with males and younger individuals. The rate of severe VI was 9.1% (95% CI: 8.8
      10.6) and was higher among males (11.6%) and those 350 years (12.3%). There could
      be 880 people with bilateral SVI in the study area. Bilateral severe VI was
      attributed to cataracts in 63% and was attributed to refractive error in 18%.
      CONCLUSION: Visual impairment and blindness in the study population was low and
      mainly due to cataract and refractive errors. Initiatives should be addressed by
      health care services to further reduce avoidable blindness in the region.

PMID- 30208145
TI  - Oral omega 3 in different proportions of EPA, DHA, and antioxidants as adjuvant
      in treatment of keratoconjunctivitis sicca in dogs.
AB  - PURPOSE: To compare the efficacy of 0.03% to-pical tacrolimus in combination with
      oral omega (omega) 3 with different ratios of eicosapentaenoic acid (EPA),
      docosahexaenoic acid (DHA), and antioxidants as adjuvant in the treatment of
      keratoconjunctivitis sicca (KCS) in dogs. METHODS: Forty-five dogs with KCS were
      evaluated monthly for 6 months. Evaluations included performance of the Schirmer
      tear, fluorescein, and lissamine green tests. Tear film break-up time (TBUT) was
      assessed. Conjunctival cytology was evaluated at the beginning, middle, and end
      of the study. Conjunctiva was biopsied at the beginning and end of the study.
      Dogs were randomly assigned to one of the three groups (n=15): Group T (topical
      tacrolimus 0.03%), Group TO (topical tacrolimus + omega-1.5 EPA: 1 DHA), or Group
      TOA (topical tacrolimus + omega-1 EPA:4.5 DHA + antioxidants). RESULTS: There was
      a significant improvement in clinical signs in all groups. TBUT increased
      throughout treatment in all groups; this effect was most pronounced in Group TO.
      Cytological analysis performed at the end of the study period, showed decreased
      levels of lymphocytes, neutrophils, and metaplastic and squamous cells in Groups
      T, TO, and TOA. Histological analysis performed at the end of the study period
      showed decreased levels of lymphocytes and neutrophils and increased levels of
      goblet cells. These effects were most pronounced in Group TO. CONCLUSION: Oral
      treatment with omega-3 containing a higher proportion of EPA than DHA increased
      the effectiveness of topical tacrolimus 0.03% in the treatment of
      keratoconjunctivitis sicca in dogs.

PMID- 30208146
TI  - Cilioretinal artery branch avulsion secondary to surgical embolectomy: management
      and outcome. Case report.
AB  - We report the trans-operative approach and short-term outcome for a patient who
      suffered a traumatic avulsion of the cilioretinal artery branch during the
      surgical management of a cilioretinal arterial branch occlusion with intraocular
      embolectomy. The patient underwent a pars plana vitrectomy with in situ
      embolectomy. The blocked artery was incised using 25 Ga vertical scissors, and
      embolus manipulation was performed using microsurgical forceps. During embolus
      extraction, the occluded cilioretinal artery and its branch were inadvertently
      avulsed and torn with subsequent intense bleeding. Laser and endodiathermy were
      used for acute hemostasis. The maneuvers created an unintended retinochoroidal
      anastomosis. Visual-field improvement was noted three months after the surgery.
      In the event of a complicated surgical embolectomy with the avulsion of the
      artery, the formation of a retinochoroidal anastomosis and reperfusion of the
      occluded artery may occur along with the improvement of the visual field in some
      cases.

PMID- 30208148
TI  - Exfoliation syndrome associated with LOXL1 gene polymorphisms in a Black patient
      from Latin America: a case report.
AB  - A 89-year-old Black female with a 6-year history of advanced open-angle glaucoma
      was referred to the Glaucoma Service of the Ophthalmology Department - Federal
      University of Sao Paulo (UNIFESP). Best-corrected visual acuity was 20/400 in the
      right eye and 20/60 in the left eye. Pseudoexfoliation material was observed at
      the iris border, angle, and the anterior lens surface. Anterior biomicroscopy
      revealed exfoliation material forming an evident peripheral zone and a central
      disc separated by a clear intermediate zone on the anterior lens surface OU.
      Gonioscopy showed an open-angle Sampaolesis's line and whitish material deposits
      OU. Fundus examination revealed a cup-to-disc ratio of 1.0 OU with peripapillary
      atrophy. Genetic analysis for single nucleo-tide polymorphisms of the lysyl
      oxidase-like 1 gene linked to exfoliation syndrome identified two such single
      nucleotide polymorphisms, rs1048661 and rs216524.

PMID- 30208147
TI  - The role of a femtosecond laser in congenital cataract associated with aniridia.
AB  - A patient with bilateral aniridia and progressive congenital cataract was treated
      at the age of 7 years through phacoaspiration with femtosecond laser capsulotomy,
      in-the-bag intraocular lens implantation, and pars plana vitrectomy (combined
      with posterior capsulotomy). The diameter of the planned anterior capsulotomy was
      4.7 mm; however, due to elevated tension in the young capsular bag, the
      capsulotomy diameter increased (to around 6 mm) shortly after release of the
      tension by the laser. In addition, the patient had a very flat and small cornea,
      causing the formation of air bubbles in the curved laser interface. This was
      addressed by filling the gap by using a viscoelastic. A very similar situation
      was observed in both eyes. Use of the femtosecond laser facilitated a successful
      outcome in a complex congenital cataract case with a safe capsulotomy that
      ensured in-the-bag intraocular lens placement.

PMID- 30208149
TI  - Ophthalmological findings in ectodermal dysplasia, ectrodactyly, and macular
      dystrophy syndrome: a case report.
AB  - We report on a case of two sisters, daughters of consanguineous parents,
      presenting with a similar condition of low visual acuity associated with retinal
      dystrophy in both eyes associated with alopecia and bone alterations or
      syndactyly.

PMID- 30208151
TI  - Intracameral moxifloxacin after cataract surgery: a prospective studyResponse:
      Intracameral moxifloxacin after cataract surgery: a prospective studyLong-term
      safety of intracameral moxifloxacin after cataract surgeryIntracameral
      antibiotics during cataract surgery: evidence and barriers.

PMID- 30208150
TI  - Nature as a source of drugs for ophthalmology.
AB  - Nature has always provided an unlimited source of biologically-active compounds.
      Since the beginning of mankind, humans have sought resources in fauna and flora
      to treat eye diseases. However, it was only after the Industrial Revolution that
      extracts of plants and substances of animal origin could be used safely, as has
      been determined by controlled interventional studies. Two major challenges faced
      by ocular pharmacology are the following: developing drugs that are able to
      reduce blindness due to glaucoma; and controlling the pain associated with eye
      surgery. The search for a drug that effectively lowers intraocular pressure and
      controls the progression of glaucoma has led to the development of various ocular
      hypotensive agents, such as physostigmine from the Physostigma venenosum plant.
      The anesthetic properties of cocaine, extracted from Erythroxylon coca, finally
      enabled surgical procedures in the eye. Several new natural compounds have been
      investigated in an attempt to identify substances with the potential to provide
      additional benefits to eye tissue and vision. Emerging evidence of anti
      inflammatory, wound-healing, antimicrobial, antioxidant, antitumor, and
      antiangiogenic properties attributed to plant extracts and animal tissues has
      encouraged more investment in research in this area. Despite technological
      advances in synthesizing drugs, the pharmaceutical industry still seeks new
      active compounds from natural sources as well as from revisiting already
      established naturally derived compounds. Although a large number of naturally
      occurring compounds is known, this review article focuses on the bioactive
      substances with scientifically-proven benefits for ocular tissues.

PMID- 30208152
TI  - Fracture risk assessment in home care patients using the FRAX(r) tool.
AB  - OBJECTIVE: To assess the ten-year risk of hip and osteoporotic fracture in home
      care patients using the FRAX(r) tool. METHODS: A retrospective, cross-sectional
      observational study including patients aged >= 40 and <= 90 years and receiving
      home care from a private provider. The risk of fracture was calculated using an
      online calculator. High risk was defined as risk of hip fracture greater than 3%
      or risk of osteoporotic fracture greater than 20%. Data were expressed as
      absolute number (n), relative frequency (%), mean, standard deviation (+/-) and
      probability value (p). RESULTS: Eighty-three (37.7%) out of 222 patients were at
      high risk of fracture. Of these, 81 (36.7%) were at high risk of hip fracture, as
      follows: 18 patients aged 70-80 years (17 female) and 63 patients aged 80-90
      years (51 female). High risk of osteoporotic fracture was limited to two female
      patients (0.1%) aged over 80 years. CONCLUSION: FRAX(r) analysis revealed similar
      fracture risks in the sample and the older adult population overall. Prospective
      investigation of fracture rates in home care patients, identification of true
      risk factors and construction of a home care patient-specific clinical score are
      warranted.

PMID- 30208153
TI  - Trends in surgical treatment of femoral neck fractures in the elderly.
AB  - OBJECTIVE: To analyze recent demographic and medical billing trends in treatment
      of femoral neck fracture of American elderly patients. METHODS: The American
      College of Surgeons National Surgical Quality Improvement Program database was
      analyzed from 2006 to 2015, for patients aged 65 years and older, using the
      Current Procedural Terminology codes 27130, 27125, 27235, and 27236. Patient
      demographics, postoperative complications, and frequency of codes were compared
      and analyzed over time. Our sample had 17,122 elderly patients, in that, 70% were
      female, mean age of 80.1 years (standard deviation+/-6.6 years). RESULTS: The
      number of cases increased, but age, gender, body mass index, rates of diabetes
      and smoking did not change over time. Open reduction internal fixation was the
      most commonly billed code, with 9,169 patients (53.6%), followed by
      hemiarthroplasty with 5,861 (34.2%) patients. Combined estimated probability of
      morbidity was 9.8% (standard deviation+/-5.2%), and did not change significantly
      over time. Postoperative complication rates were similar between treatments.
      CONCLUSION: Demographics and morbidity rates in femoral neck fractures of elderly
      patients did not change significantly from 2006 to 2015. Open reduction internal
      fixation was the most common treatment followed by hemiarthroplasty.

PMID- 30208155
TI  - Organizational commitment, psychometric qualities and invariance of the Meyer and
      Allen Questionnaire for Portuguese Nurses1.
AB  - OBJECTIVE: to evaluate the psychometric qualities of the Portuguese version of
      the Organizational Commitment Questionnaire for the nursing context, through
      confirmatory analysis and invariance, aiming to evaluate the reliability,
      internal consistency, construct validity and external validity of the instrument.
      METHOD: confirmatory factor analysis of the Portuguese version of the
      questionnaire was carried out with a sample of 850 nurses, in hospital context.
      The analysis was complemented using specification search. Goodness of fit was
      evaluated through different indices. Reliability, internal consistency and
      construct validity were estimated. The invariance of the model was evaluated in
      two subsamples of the same sample, in order to confirm the external validity of
      the factorial solution. RESULTS: the refined model demonstrated good overall fit
      (chi2/df=6.37; CFI=0.91; GFI=0.92; RMSEA=0.08; MECVI=0.62). The factorial
      structure was stable (lambda:Deltachi2(14)=18.31; p=0;193; Intercepts:
      Deltachi2(14)=22.29; p=0.073; Covariance: Deltachi2(3)=6.01; p=0.111; Residuals:
      Deltachi2(15)=22.44; p=0.097). CONCLUSION: the simplified model of the
      questionnaire demonstrated adequate goodness of fit, representing a stable
      factorial solution. The instrument was fit to monitor and evaluate the
      organizational commitment of Portuguese nurses.

PMID- 30208154
TI  - Temporomandibular joint disorders as the only manifestation of juvenile
      idiopathic arthritis: a case report.
AB  - Juvenile idiopathic arthritis is a term used to include all chronic childhood
      arthritis of unknown etiology. It is characterized by chronic inflammation
      persisting for at least 6 weeks, beginning before 16 years of age. The
      characteristics present are chronic synovitis, arthralgia, impaired joint
      mobility in at least one joint, and erosion with destruction of cartilage and
      subchondral bone, that could be associated or not with systemic involvement,
      according to each subtype of the disease. During the pathologic process, the
      temporomandibular joint can be involved by the juvenile idiopathic arthritis,
      resulting in severe mandibular dysfunction, with higher frequency in female
      patients. Initially, these lesions can show minor alterations like flattening of
      the condyle, erosions, and evolve to severe lesions, like destruction of the head
      of the condyle. We report a case of male patient who had destruction of both
      condyles, as a result from juvenile idiopathic arthritis. Proposed mechanisms to
      explain the juvenile idiopathic arthritis was reviewed. In this report the
      patient did not have pain or inflammatory process, and the temporomandibular
      diseases was the only manifestation.

PMID- 30208156
TI  - Physical frailty prediction model for the oldest old1.
AB  - OBJECTIVE: to present a physical frailty prediction model for oldest old users of
      primary health care, according to clinical variables. METHOD: cross-sectional
      study with proportional stratified sample of 243 oldest old subjects. Data were
      collected through a structured clinical questionnaire, handgrip strength test,
      walking speed, weight loss, fatigue/exhaustion, and physical activity level. For
      the analysis of the data, univariate and multivariate analysis by logistic
      regression were used (p<0.05), which resulted in prediction models. The odds
      ratios (95% Confidence Interval) of the models were calculated. Each model was
      evaluated by deviance analysis, likelihood ratios, specificity and sensitivity,
      considering the most adequate. All ethical and legal precepts were followed.
      RESULTS: the prediction model elected was composed of metabolic diseases,
      dyslipidemias and hospitalization in the last 12 months. CONCLUSION: clinical
      variables interfere in the development of the physical frailty syndrome in oldest
      old users of basic health unit. The choice of a physical frailty regression model
      is the first step in the elaboration of clinical methods to evaluate the oldest
      old in primary care.

PMID- 30208157
TI  - Effectiveness of auriculotherapy on anxiety during labor: a randomized clinical
      trial1.
AB  - OBJECTIVE: to evaluate the effectiveness of auriculotherapy on the anxiety of
      women during labor. METHOD: this is a randomized, parallel, triple-blind clinical
      trial. 102 parturients with gestational age >= 37 weeks, cervical dilatation >= 4
      cm and two or more contractions in 10 min were selected and randomly assigned
      into three groups to receive auriculotherapy, placebo or control (routine care).
      Auriculotherapy was applied with crystal microspheres to the shenmen, uterus,
      neurasthenia area and endocrine points, and anxiety was assessed by the Hamilton
      Anxiety Rating Scale (HAM-A). Analyzes were performed using the Kruskal-Wallis,
      Generalized estimating equations, Chi-square and Fisher's exact tests. RESULTS:
      the groups showed no significant difference at baseline according to the HAM-A.
      After the intervention there was a significant increase in HAM-A scores at 120
      min in the placebo versus auriculotherapy group (mean difference (MD) 3.62,
      confidence interval (CI) 0.42-6.81, p=0.0265) and control versus auriculotherapy
      group (MD 4.88, CI 1.87-7.88, p=0.0015). CONCLUSION: the parturients with
      auriculotherapy presented lower levels of anxiety according to the HAM-A score
      after the treatment when compared to the women from the other groups; this can
      represent alternative care in obstetric practice. Registration: n. RBR-47hhbj.

PMID- 30208158
TI  - Breastfeeding self-efficacy and postpartum depression: a cohort study.
AB  - OBJECTIVE: to evaluate breastfeeding self-efficacy, the presence of postpartum
      depression symptons and the association between breastfeeding self-efficacy and
      postpartum depression with cessation of exclusive breastfeeding. METHOD: cohort
      study with 83 women. The instruments used were the Breastfeeding Self-Efficacy
      Scale and the Edinburgh Postnatal Depression Scale. Statistical analysis was
      conducted using the log-rank tests, analysis of variance and the Cox survival
      model. RESULTS: breastfeeding self-efficacy (p = 0.315) and postpartum depression
      (p = 0.0879) did not show any statistical difference over time. The chances of
      cessation of exclusive breastfeeding decreased by 48% when self-efficacy changed
      from low to medium and by 80% when it changed from medium to high. Postpartum
      women who scored >=10 on the Edinburgh Postnatal Depression Scale interrupt
      exclusive breastfeeding, on average, 10 days earlier than those with a score <=9,
      whose median breastfeeding duration was 38 days postpartum. CONCLUSION:
      breastfeeding self-efficacy was proved to be a protective factor for exclusive
      breastfeeding, while postpartum depression is a risk factor.

PMID- 30208159
TI  - Validity and reliability of the Clinical Learning Environment, Supervision and
      Nurse Teacher (CLES+T), Turkish version1.
AB  - OBJECTIVE: A methodological type of study was conducted for the purpose of
      investigating the validity and reliability of the Turkish version of the Clinical
      Learning Environment, Supervision and Nurse Teacher (CLES+T) evaluation scale of
      the clinical learning environment of students, clinical nurses, and educators.
      METHODS: Sample was comprised of 602 Turkish nursing students with clinical
      practice experience at the hospital. The CLES+T, developed by Saarikoski, was
      used for data collection. Language equivalency, internal consistency, item-total
      correlation, and structure validity were conducted within the scope of the
      validity and reliability study on the CLES +T scale. RESULTS: It was determined
      that item-total correlations of four items were lower than 0.30, and those items
      were removed from the scale as a result of item analysis. The Cronbach's alpha
      value of the scale was 0.93-0.99; item total point correlations of the scale
      varied between 0.45 and 0.66; six factors were identified in the CLES+T factor
      analysis study, with a total variance explained by these six factors of 64%.
      CONCLUSION: According to the findings of the research, the CLES+T Turkish version
      was found to be a valid and reliable scale, which can be used to evaluate
      satisfaction of nursing students with their clinical education in Turkey.

PMID- 30208160
TI  - Non-technical skills assessment scale in nursing: construction, development and
      validation1.
AB  - OBJECTIVES: The introduction of non-technical skills during nursing education is
      crucial to prepare nurses for the clinical context and increase patient safety.
      We found no instrument developed for this purpose. to construct, develop and
      validate a non-technical skills assessment scale in nursing. METHOD:
      methodological research. Based on the literature review and experience of
      researchers on non-technical skills in healthcare and the knowledge of the
      principles of crisis resource management, a list of 63 items with a five-point
      Likert scale was constructed. The scale was applied to 177 nursing undergraduate
      students. Descriptive statistics, correlations, internal consistency analysis and
      exploratory factor analysis were performed to evaluate the psychometric
      properties of the scale. RESULTS: scale items presented similar values for mean
      and median. The maximum and the minimum values presented a good distribution
      amongst all response options. Most items presented a significant and positive
      relationship. Cronbach alpha presented a good value (0.94), and most correlations
      were significant and positive. Exploratory factor analysis using the Kaiser-Meyer
      Olkin test showed a value of 0.849, and the Bartlett's test showed adequate
      sphericity values (chi2=6483.998; p=0.000). One-factor model explained 26% of the
      total variance. CONCLUSION: non-technical skills training and its measurement
      could be included in undergraduate or postgraduate courses in healthcare
      professions, or even be used to ascertain needs and improvements in healthcare
      contexts.

PMID- 30208161
TI  - Emergency nurses' attitudes towards the concept of witnessed resuscitation.
AB  - OBJECTIVE: to review the most relevant evidence on the nurses' attitudes towards
      witnessed resuscitation, in the inpatient and out-of-hospital spheres. METHOD:
      integrative literature review, covering the period from 2008 till 2015, using the
      databases PubMed, Lilacs and SciELO; in Spanish, English and Portuguese. The
      pediatric context was excluded from the study. RESULTS: the synthesis of the data
      resulted in the inclusion of 10 articles, categorized as: positive attitudes and
      negative attitudes. CONCLUSIONS: discrepancies exist among the nurses from
      different contexts and geographical regions towards the concept; protocols need
      to be established for this situation, in view of the advantages evidenced in the
      literature, for the nursing professionals as well as the relatives. Witnessed
      resuscitation can represent an opportunity to understand and cope with the
      rational and irrational in the situation in a shared manner, as well as mitigate
      or dignify the mourning.

PMID- 30208163
TI  - Revisiting the roles of VHR/DUSP3 phosphatase in human diseases.
AB  - Protein tyrosine phosphatases have long been considered key regulators of
      biological processes and are therefore implicated in the origins of various human
      diseases. Heterozygosity, mutations, deletions, and the complete loss of some of
      these enzymes have been reported to cause neurodegenerative diseases, autoimmune
      syndromes, genetic disorders, metabolic diseases, cancers, and many other
      physiological imbalances. Vaccinia H1-related phosphatase, also known as dual
      specificity phosphatase 3, is a protein tyrosine phosphatase enzyme that
      regulates the phosphorylation of the mitogen-activated protein kinase signaling
      pathway, a central mediator of a diversity of biological responses. It has been
      suggested that vaccinia H1-related phosphatase can act as a tumor suppressor or
      tumor-promoting phosphatase in different cancers. Furthermore, emerging evidence
      suggests that this enzyme has many other biological functions, such as roles in
      immune responses, thrombosis, hemostasis, angiogenesis, and genomic stability,
      and this broad spectrum of vaccinia H1-related phosphatase activity is likely the
      result of its diversity of substrates. Hence, fully identifying and
      characterizing these substrate-phosphatase interactions will facilitate the
      identification of pharmacological inhibitors of vaccinia H1-related phosphatase
      that can be evaluated in clinical trials. In this review, we describe the
      biological processes mediated by vaccinia H1-related phosphatase, especially
      those related to genomic stability. We also focus on validated substrates and
      signaling circuitry with clinical relevance in human diseases, particularly
      oncogenesis.

PMID- 30208162
TI  - Metformin and blood cancers.
AB  - Type 2 diabetes mellitus and cancer are correlated with changes in insulin
      signaling, a pathway that is frequently upregulated in neoplastic tissue but
      impaired in tissues that are classically targeted by insulin in type 2 diabetes
      mellitus. Many antidiabetes treatments, particularly metformin, enhance insulin
      signaling, but this pathway can be inhibited by specific cancer treatments. The
      modulation of cancer growth by metformin and of insulin sensitivity by anticancer
      drugs is so common that this phenomenon is being studied in hundreds of clinical
      trials on cancer. Many meta-analyses have consistently shown a moderate but
      direct effect of body mass index on the incidence of multiple myeloma and
      lymphoma and the elevated risk of leukemia in adults. Moreover, new
      epidemiological and preclinical studies indicate metformin as a therapeutic agent
      in patients with leukemia, lymphomas, and multiple myeloma. In this article, we
      review current findings on the anticancer activities of metformin and the
      underlying mechanisms from preclinical and ongoing studies in hematologic
      malignancies.

PMID- 30208167
TI  - Interdisciplinary interventions in the perioperative rehabilitation of total
      laryngectomy: an integrative review.
AB  - The aim of this study was to use the scientific literature to identify
      interdisciplinary interventions for rehabilitation during the perioperative
      period for cancer patients who underwent total laryngectomy. We systematically
      researched controlled descriptors: laryngectomy, patient care team/education,
      patient care team/manpower, patient care team/methods, patient care
      team/utilization and rehabilitation. We performed a qualitative narrative
      synthesis and identified 549 articles. Of these, 113 were duplicates, 398 were
      excluded during the analysis of the title and abstract, 1 was excluded for
      unfeasibility of access, and 4 were excluded after reading the article in full,
      resulting in 33 included articles. The articles addressed different types of
      interdisciplinary actions, such as vocal, olfactory, pulmonary and alimentary
      rehabilitation; comparisons of prosthetic devices; and descriptions of practices
      for total laryngectomized patient rehabilitation. Although the interventions
      found in the literature were effective in the rehabilitation of the total
      laryngectomized patient, their interdisciplinarity was not evidenced but was
      highlighted in these studies as a factor for improvement in terms of practical
      assistance and quality of life.

PMID- 30208166
TI  - Perspectives for cancer immunotherapy mediated by p19Arf plus interferon-beta
      gene transfer.
AB  - While cancer immunotherapy has gained much deserved attention in recent years,
      many areas regarding the optimization of such modalities remain unexplored,
      including the development of novel approaches and the strategic combination of
      therapies that target multiple aspects of the cancer-immunity cycle. Our own work
      involves the use of gene transfer technology to promote cell death and immune
      stimulation. Such immunogenic cell death, mediated by the combined transfer of
      the alternate reading frame (p14ARF in humans and p19Arf in mice) and the
      interferon-beta cDNA in our case, was shown to promote an antitumor immune
      response in mouse models of melanoma and lung carcinoma. With these encouraging
      results, we are now setting out on the road toward translational and preclinical
      development of our novel immunotherapeutic approach. Here, we outline the
      perspectives and challenges that we face, including the use of human tumor and
      immune cells to verify the response seen in mouse models and the incorporation of
      clinically relevant models, such as patient-derived xenografts and spontaneous
      tumors in animals. In addition, we seek to combine our immunotherapeutic approach
      with other treatments, such as chemotherapy or checkpoint blockade, with the goal
      of reducing dosage and increasing efficacy. The success of any translational
      research requires the cooperation of a multidisciplinary team of professionals
      involved in laboratory and clinical research, a relationship that is fostered at
      the Cancer Institute of Sao Paulo.

PMID- 30208165
TI  - DNA repair pathways and cisplatin resistance: an intimate relationship.
AB  - The main goal of chemotherapeutic drugs is to induce massive cell death in
      tumors. Cisplatin is an antitumor drug widely used to treat several types of
      cancer. Despite its remarkable efficiency, most tumors show intrinsic or acquired
      drug resistance. The primary biological target of cisplatin is genomic DNA, and
      it causes a plethora of DNA lesions that block transcription and replication.
      These cisplatin-induced DNA lesions strongly induce cell death if they are not
      properly repaired or processed. To counteract cisplatin-induced DNA damage, cells
      use an intricate network of mechanisms, including DNA damage repair and
      translesion synthesis. In this review, we describe how cisplatin-induced DNA
      lesions are repaired or tolerated by cells and focus on the pivotal role of DNA
      repair and tolerance mechanisms in tumor resistance to cisplatin. In fact,
      several recent clinical findings have correlated the tumor cell status of DNA
      repair/translesion synthesis with patient response to cisplatin treatment.
      Furthermore, these mechanisms provide interesting targets for pharmacological
      modulation that can increase the efficiency of cisplatin chemotherapy.

PMID- 30208164
TI  - The human adrenal cortex: growth control and disorders.
AB  - This review summarizes key knowledge regarding the development, growth, and
      growth disorders of the adrenal cortex from a molecular perspective. The adrenal
      gland consists of two distinct regions: the cortex and the medulla. During
      embryological development and transition to the adult adrenal gland, the adrenal
      cortex acquires three different structural and functional zones. Significant
      progress has been made in understanding the signaling and molecules involved
      during adrenal cortex zonation. Equally significant is the knowledge obtained
      regarding the action of peptide factors involved in the maintenance of zonation
      of the adrenal cortex, such as peptides derived from proopiomelanocortin
      processing, adrenocorticotropin and N-terminal proopiomelanocortin. Findings
      regarding the development, maintenance and growth of the adrenal cortex and the
      molecular factors involved has improved the scientific understanding of disorders
      that affect adrenal cortex growth. Hypoplasia, hyperplasia and adrenocortical
      tumors, including adult and pediatric adrenocortical adenomas and carcinomas, are
      described together with findings regarding molecular and pathway alterations.
      Comprehensive genomic analyses of adrenocortical tumors have shown gene
      expression profiles associated with malignancy as well as methylation alterations
      and the involvement of miRNAs. These findings provide a new perspective on the
      diagnosis, therapeutic possibilities and prognosis of adrenocortical disorders.

PMID- 30208170
TI  - [Dialogues on the work process in oral health in Brazil: an analysis based on the
      PMAQ-AB survey].
AB  - The study aimed to: (1) describe the work process in Brazil's oral health teams,
      based on the essential attributes of primary health care, according to geographic
      region, type of team, and the municipality's socioeconomic characteristics and
      (2) verify whether the data in the work process of the oral health teams in the
      Brazilian National Program to Improve Access and Quality in primary health (PMAQ
      AB) were capable of measuring such attributes. This was a nationwide ecological
      study with data from cycle I of PMAQ-AB. The study included descriptive,
      exploratory factor, and confirmatory factor analyses (alpha = 5%). Constructs
      were analyzed in light of the essential attributes of primary health care (first
      contact, coordination of care, comprehensiveness, and continuity). The first
      three constructs and a fourth factor were formed, called dental prosthesis
      actions. However, the continuity attribute was not formed. The models' goodness
      of-fit measures were satisfactory. Factor loads were greater than 0.5, except for
      the two variables in factor 3. The actions most frequently performed by the oral
      health teams (> 60%) were in first contact, and the least frequent were those in
      comprehensiveness, highlighting referrals to specialties (7.6%). There were
      differences in the work process in oral health teams between regions of the
      country, type of team, and certification strata (p < 0.05). In conclusion, data
      on the work process in oral health teams from cycle primary health care in the
      services' work routine. Further research is recommended on continuity of care. In
      addition, the oral health teams participating in cycle I of PMAQ-AB should make
      further progress in actions related to comprehensiveness and coordination of
      care.

PMID- 30208172
TI  - Diabetes research in Mexico: a map of 13 years of public funding.
AB  - In Mexico, diabetes represents a serious public health problem and a high-cost
      disease for the health system. Health research is essential for generating new
      knowledge to combat such a serious issue, however, there is not enough
      information on how to generate and use it. This paper examines the public funding
      of 303 diabetes research projects, granted by the National Council of Science and
      Technology in Mexico between 2002 and 2014. The projects were systematized and
      classified according to their type of research, discipline or subject, and aim of
      knowledge. Considering these information, an econometric model that links the
      funding with the characteristics of the projects was prepared. The results show
      that the funding is focused on the basic and biomedical areas, particularly on
      genetic research, and also that diabetes research resources have increased over
      time, not steadily, but rather cyclically. In diabetes research projects there is
      a high level of concentration at several dimensions: research areas, topics,
      objects, institutions conducting research, and regions. The analysis of the
      resource allocation suggests that Mexico needs a stronger and oriented diabetes
      research agenda, including in its bases discussions about balance between basic
      and applied research, and about oriented research towards practical
      implementations. The importance of promoting health systems research to improve
      diabetes care is also discussed, as well as implementing mechanisms to assess the
      impact of diabetes research in short, medium and long term, as part of Mexico's
      science and technology policy.

PMID- 30208171
TI  - Triggers for active surveillance of adverse drug events in newborns.
AB  - The study aimed to verify the application and performance of triggers for adverse
      drug events in hospitalized newborns. This prospective cohort study was conducted
      in the neonatal care units of a university hospital from March to September 2015.
      A list of triggers was developed for the identification of adverse drug events in
      this population. The list included antidote, clinical, and laboratory triggers. A
      total of 125 newborns who had received drugs during the hospitalization were
      included. Neonatal patient charts were screened to detect triggers. When a
      trigger was found, the patient chart was reviewed to identify possible adverse
      drug events. Each trigger's yield in the identification of adverse drug events
      was calculated and then classified according to its performance. Nine hundred and
      twenty-five triggers identified 208 suspected adverse drug events. The triggers'
      overall yield was 22.5%. The most frequently identified triggers were: drop in
      oxygen saturation, increased frequency of bowel movements, medications stop, and
      vomiting. The triggers with the best performance in the identification of adverse
      drug events were: increased creatinine, increased urea, necrotizing
      enterocolitis, prescription of flumazenil, hypercalcemia, hyperkalemia,
      hypernatremia, and oversedation. The triggers identified in this study can be
      used to track adverse drug events in similar neonatal care services, focusing on
      the triggers with the best performance and the lowest workload in the
      identification.

PMID- 30208169
TI  - Alterations in the expression and activity of extracellular matrix components in
      HPV-associated infections and diseases.
AB  - Infection with human papillomaviruses is associated with a series of benign and
      malignant hyperproliferative diseases that impose a heavy burden on human
      populations. A subgroup of mucosal human papillomavirus types are associated with
      the majority of cervical cancers and a relevant fraction of vulvar, vaginal,
      anal, penile and head and neck carcinomas. Human papillomaviruses mediate cell
      transformation by the expression of two pleiotropic oncoproteins that alter major
      cellular regulatory pathways. However, these viruses are not complete
      carcinogens, and further alterations within the infected cells and in their
      microenvironment are necessary for tumor establishment and progression.
      Alterations in components of the extracellular matrix for instance, matrix
      metalloproteinases and some of their regulators such as tissue inhibitors of
      metalloproteinases, have been consistently reported in human papillomaviruses
      associated diseases. Matrix metalloproteinases function by remodeling the
      extracellular matrix and alterations in their expression levels and/or activity
      are associated with pathological processes and clinical variables including local
      tumor invasion, metastasis, tumor relapse and overall patient prognosis and
      survival. In this review we present a summarized discussion on the current data
      concerning the impact of human papillomavirus infection on the activity and
      expression of extracellular matrix components. We further comment on the
      possibility of targeting extracellular matrix molecules in experimental treatment
      protocols.

PMID- 30208168
TI  - Human papillomavirus and genome instability: from productive infection to cancer.
AB  - Infection with high oncogenic risk human papillomavirus types is the etiological
      factor of cervical cancer and a major cause of other epithelial malignancies,
      including vulvar, vaginal, anal, penile and head and neck carcinomas. These
      agents affect epithelial homeostasis through the expression of specific proteins
      that deregulate important cellular signaling pathways to achieve efficient viral
      replication. Among the major targets of viral proteins are components of the DNA
      damage detection and repair machinery. The activation of many of these cellular
      factors is critical to process viral genome replication intermediates and,
      consequently, to sustain faithful viral progeny production. In addition to the
      important role of cellular DNA repair machinery in the infective human
      papillomavirus cycle, alterations in the expression and activity of many of its
      components are observed in human papillomavirus-related tumors. Several studies
      from different laboratories have reported the impact of the expression of human
      papillomavirus oncogenes, mainly E6 and E7, on proteins in almost all the main
      cellular DNA repair mechanisms. This has direct consequences on cellular
      transformation since it causes the accumulation of point mutations, insertions
      and deletions of short nucleotide stretches, as well as numerical and structural
      chromosomal alterations characteristic of tumor cells. On the other hand, it is
      clear that human papillomavirus-transformed cells depend on the preservation of a
      basal cellular DNA repair activity level to maintain tumor cell viability. In
      this review, we summarize the data concerning the effect of human papillomavirus
      infection on DNA repair mechanisms. In addition, we discuss the potential of
      exploiting human papillomavirus-transformed cell dependency on DNA repair
      pathways as effective antitumoral therapies.

PMID- 30208173
TI  - Comprehensiveness of practices by Cuban physicians in the More Doctors Program in
      Rio de Janeiro, Brazil.
AB  - The shortage of physicians in remote and underprivileged areas poses an obstacle
      to universal access and quality of health care. Through the More Doctors Program
      (PMM), as of 2015, 18 thousand physicians had been incorporated into Brazil's
      Unified National Health System (SUS) to work in basic care, 79% of whom were
      Cubans. This article analyzed the comprehensiveness of practices by Cuban
      physicians in the PMM using a qualitative study in the city of Rio de Janeiro,
      Brazil, based on interviews with Cuban physicians (24) and a focus group with
      supervisors of the PMM (4). Comprehensiveness was analyzed in two dimensions: the
      community-oriented biopsychosocial approach to care and the range of activities
      in health promotion, prevention, and care. The work by Cuban physicians presents
      elements that are consistent with the comprehensiveness of practices in primary
      care, providing a wide range of care and services, in keeping with the health
      problems' complexity and the plurality of settings. These health workers show
      outstanding capacity for community interaction, a preventive focus, planning of
      activities, and positive interpersonal team relations. The study identified
      attitudes and techniques of solidarity, physician-patient bonding, and community
      accountability. Challenges were identified in the promotion of participatory
      practices with communities, the expansion of users' autonomy in clinical
      decisions, management of psychological problems, systematization of approach
      tools, and performance of invasive procedures. The study furnishes strong
      evidence that the PMM, in addition to medical consultations, provides
      comprehensive health care and contributes to strengthening basic care in Brazil.

PMID- 30208174
TI  - Waist circumference percentile curves as a screening tool to predict
      cardiovascular risk factors and metabolic syndrome risk in Brazilian children.
AB  - The goals of this study were to develop reference values for waist circumference
      (WC) in Brazilian children between 6-10 years old and to evaluate the WC
      performance in predicting cardiovascular risk factors and metabolic syndrome
      (MetS) in children. This is a population-based epidemiological cross-sectional
      study, in which 1,397 children participated, with a 6-10 years old probability
      sampling and from public and private schools in the city of Uberaba, Minas Gerais
      State, Brazil. WC was measured at the waist narrowest point (WC1) and at the
      umbilicus level (WC2). Blood samples and blood pressure were collected to
      determine the MetS diagnosis. There was a significant effect of age (p = 0.001),
      anatomical point (WC1 vs. WC2, p = 0.001) and sex-anatomical point interaction (p
      = 0.016) for WC. Smoothed sex- and age-specific 5th, 10th, 25th, 50th, 75th, 90th
      and 95th percentile curves of WC1 and WC2 were designed by the LMS method. WC was
      accurate to predict MetS, for all ages [area under the ROC curve (AUC) > 0.79 and
      p < 0.05], regardless of sex. This study presented percentile curves for WC at
      two anatomical points in a representative sample of Brazilian children.
      Furthermore, WC was shown to be a strong predictor of cardiovascular risk factors
      and MetS in children.

PMID- 30208175
TI  - [Intraurban differentials in congenital syphilis: a predictive analysis by
      neighborhood in the city of Rio de Janeiro, Brazil].
AB  - The study aimed to characterize notified cases of congenital syphilis from 2011
      to 2014 in the city of Rio de Janeiro and to analyze possible associations
      between congenital syphilis and living conditions in the city's neighborhoods.
      Cases of congenital syphilis were characterized according to biological and
      socioeconomic variables and health services use. At the aggregate level,
      regression tree technique was used for the data analysis, with mean incidence
      rate (2011-2014) of congenital syphilis as the dependent variable and housing
      quality, schooling, income, teenage pregnancy, poverty density, access to
      prenatal care, and skin color as independent variables. The dependent variable
      was mapped to identify spatial patterns. The SINAN, SINASC, and IBGE databases
      were used for notifiable diseases, live births, and census data, respectively. A
      total of 6,274 cases of congenital syphilis were reported, which represents an
      incidence rate of 17.3 cases/1,000 live births. Cases were distributed in the
      central, northern peripheral, and western zones of the city, with a high
      proportion of cases in infants of black mothers with low schooling. There was
      also a high proportion of pregnant women with late diagnosis of syphilis and
      inadequate treatment. At the aggregate level, the most relevant variable for
      explaining the problem was the low proportion of pregnant women with at least 7
      prenatal visits. The analysis allowed the identification of marginalized
      population segments and can help direct public health resources more effectively.

PMID- 30208176
TI  - Iron salts and vitamins: use, purchase and sources of obtainment among children
      in Brazil.
AB  - To verify the prevalence of use, purchase and sources of iron salts and vitamins
      by children aged from 0 to 12 years in Brazil. Population-based transversal study
      (Brazilian National Survey on Access, Utilization, and Promotion of Rational Use
      of Medicines - PNAUM), including 7,528 children up to 12 years of age.
      Information was obtained through questionnaires answered by the children's
      tutors, about the use of iron salts and vitamins 15 days before the interview;
      forms of financing, and sources of obtainment, sociodemographic characteristics,
      and presence of chronic disease. Descriptive and bivariate analyses were
      performed and the main variables were expressed by relative frequencies and 95%
      confidence intervals (95%CI). The prevalence of use of iron salts was 1.6%
      (95%CI: 1.2-2.1), with higher prevalence among children under 1 year old (8.5%;
      95%CI: 6.3-11.5) and residents of the southeastern region (2.3%; 95%CI: 1.5-3.4).
      Prevalence of use of vitamins was 4.8% (95%CI: 4.2-5.6), with higher prevalence
      among children under 1 year old (24.3%; 95%CI: 20.3-28.7) and residents of the
      northern region (8.6%; 95%CI: 6.2-11.7). Purchase occurred by direct
      reimbursement for 41.6% (95%CI: 27.9-56.7) of the iron salts, and for 82.4%
      (95%CI: 76.3-87.2) of the vitamins. The iron salts were predominantly obtained
      from SUS pharmacies (51.5%; 95%CI: 36.4-66.4), and the vitamins from commercial
      pharmacies (80.6%; 95%CI: 77.4-85.6). The results suggested the use of iron salts
      in the Brazilian pediatric population was low, with reduction in use as age
      increased, regional differences and free-of-charge obtainment, predominantly from
      SUS.

PMID- 30208177
TI  - [Biopolitics for breastfeeding: an analysis of the global and local movements and
      their links to social development discourses].
AB  - This study aimed to analyze the links between the production of biopolitics for
      breastfeeding and social development discourses after the post-war period, with a
      view towards problematizing the nature/culture dichotomy by which breastfeeding
      is often operationalized. The study adopts an anthropological perspective to
      compare biopolitics for breastfeeding with the changes in developmentalist
      discourses. The analysis of global movements by these biopolitics helped explain
      how a network of distinct entities (e.g., government agencies, multilateral
      bodies, international development agencies, and nongovernmental organizations)
      have shaped breastfeeding over time in keeping with the prevailing
      developmentalist discourses and practices. Initially, the developmentalist
      discourse focused on industrialization and modernization, and breastfeeding was
      not the focus of public policies. In the 1970s and 1980s, when the
      developmentalist discourse shifted the focus to child malnutrition and infant
      mortality, the first global biopolitics for breastfeeding were launched, and
      breastfeeding practice began to be operationalized as a means to fight these
      health problems. Meanwhile, the contemporary social development discourse also
      evokes a process of individual development. Simultaneously, biopolitics for
      breastfeeding rely on various technologies for this purpose. The conclusion is
      that developmentalist discourses act as a sociocultural reference by which
      breastfeeding is operationalized, and thus that breastfeeding is not only a
      natural process, but also a political, economic, and social one.

PMID- 30208178
TI  - The main challenge for science publishing.

PMID- 30208179
TI  - [Early neonatal near miss identified through health information systems].
AB  - The aim of this study was to validate a definition to identify cases of early
      neonatal near miss using data from health information systems (SIS in
      Portuguese). This was a concurrent validation study focusing on three definitions
      for identification of cases of early neonatal near miss among live births in a
      university hospital in 2012. Three different definitions were applied to this
      live birth cohort using the criteria birth weight, gestational age, 5-minute
      Apgar score, admission to the neonatal intensive care unit, mechanical
      ventilation, and congenital malformations, in different combinations, considering
      the proposals in two Brazilian articles (Silva et al.; Pillegi-Castro et al.) and
      a third (SIS definition) with available data from health information systems.
      Cases were defined as infants that had survived the risk conditions as of the 7th
      day of life. For concurrent validation, the study adopted early neonatal deaths
      as the reference. Of the 2,097 live births studied, 33 died in the early neonatal
      period, and the number of cases of early neonatal near miss varied according to
      the definition used: 153 (Silva definition), 194 (Pileggi-Castro definition), and
      304 (SIS definition). Sensitivity and specificity were 97% and 92.6%,
      respectively, according to the Silva definition, 90.9% and 90.6% according to the
      Pileggi-Castro definition, and 93.9% and 85.3% according to the SIS definition.
      The results show that the SIS definition has sensitivity and specificity close to
      the other definitions and suggest that it is possible to monitor early neonatal
      near miss using only data that are available in official health information
      systems.

PMID- 30208180
TI  - [Food environment: validation of a method for measurement and characterization in
      the territory with the Health Academy Program].
AB  - The study aimed to verify the validity of secondary data in the investigation of
      the food environment and to analyze the characteristics of the community
      environment and consumers in territories covered by a health promotion service.
      This was an ecological study in 18 units of the Health Academy Program in Belo
      Horizonte, Minas Gerais, Brazil, selected by simple cluster sampling. Validation
      of the establishments marketing fruits and vegetables, obtained from public
      databases, was done via telephone contact, Google Street View, and on-site audit.
      The following variables were investigated in the community food environment: type
      and location of the establishment; consumer's environment: availability, variety,
      price, and advertising of fruits and vegetables; availability and variety of
      ultra-processed foods; and hygienic and sanitary conditions. The access to
      healthy foods index was used to measure access to these foods. The on-site audit
      revealed weak concordance (45.7%) with the secondary databases. Of the 298
      establishments, the majority were bulk grocery stores and open-air markets
      (61.3%), which showed the highest availability of healthy foods, but also
      marketed large amounts of ultra-processed foods (60.7%). One-third of the
      establishments showed substandard hygienic and sanitary conditions. The secondary
      databases showed low validity, emphasizing the need to audit the establishments.
      The establishments also showed a striking presence of ultra-processed foods and
      poor hygiene and sanitation.

PMID- 30208181
TI  - Congenital Zika virus syndrome in infants: repercussions for the promotion of
      families' mental health.
AB  - This article aims to discuss the impacts of the promotion of families' mental
      health following the diagnosis of Zika virus infection in the pregnant woman
      and/or congenital Zika virus syndrome (CZVS) in the infant. The study also aims
      to foster reflection on mother-infant bonding in this context. The study is
      relevant not only because there is still so much to learn about CZVS, with its
      enormous capacity for dispersion and many doubts as to the physical consequences
      and psychological impacts, but also due to the urgent need to provide families
      and/or caregivers with guidelines for care and alternatives for dealing with the
      illness. The study was conducted in an outpatient clinic specifically providing
      care to children with CZVS at the Unit for Infectious Diseases in Pediatrics in a
      tertiary hospital of the Brazilian Unified National Health System (SUS) in Rio de
      Janeiro, Brazil. The team is multidisciplinary, and each member conducts an
      assessment based on their specific field of knowledge. This qualitative study
      drew on participant observation, and the data analysis showed that the use of
      virtual social networks, which function (independently of the medicine
      approaches) as channels for communication and collective discussion of the
      different experiences, in order to share strategies to overcome the diagnosed
      impossibilities.

PMID- 30208182
TI  - [Assessment of vaccination coverage of children in a medium-sized Brazilian city
      using electronic immunization registry].
AB  - Administrative data show high vaccination coverage rates in Brazil, but there is
      no assessment of the validity and timeliness of dose administration, or whether
      the vaccination schedule is complete. This study assessed timely and updated
      coverage rates in children 12 to 24 months of age. This was a longitudinal
      population-based study in Araraquara, Sao Paulo State, a predominantly urban
      medium-sized municipality, using the Juarez System, an electronic immunization
      registry (EIR). Coverage rates were assessed in 49,741 children born from 1998 to
      2013, a period in which five different vaccination schedules were used. Trends
      were estimated with the Prais-Winsten linear regression method. Updated coverage
      of the complete schedule varied from 79.5% to 91.3% at 12 months and from 75.8%
      to 86.9%, at 24 months. Timely coverage (all doses applied at the recommended
      ages, with no delays) ranged from 53.3% to 74% at 12 months and from 36.7% to
      53.8% at 24 months. There was an upward trend in updated coverage at 24 months.
      The delays in relation to recommended age increased starting at six months and
      appeared to relate more to age than to the number of doses in the schedule. The
      proportion of invalid and late doses was lower than in other studies. Despite the
      increase in the number of doses in the vaccination schedule, the study showed
      high updated coverage rates and higher timely coverage than reported in the
      national and international literature; however, more effort is needed to increase
      timeliness. EIR proved relevant for assessing and monitoring vaccination coverage
      with more accurate analyses.

PMID- 30208183
TI  - Understanding fatness in the public sphere of young students: social
      representations and emotional response.
AB  - This study examines how youth collectively represent fatness and determines the
      emotions it arouses. Understanding how fatness is socially constructed by young
      people is crucial to create programs that better deal with it. A free association
      exercise elicited by the word "fatness" was answered by 200 people of the
      Autonomous Community of the Basque Country (Spain), and the content was analyzed
      by its lexicon using Alceste software. The results showed that health-related
      representation of fatness was mostly descriptive, and it was not connected to
      risky or any emotional response. But fatness was also completely represented as a
      social pressure issue related to stigmatization and highly correlated with
      negative emotions, such as sadness, insecurity, embarrassment, anguish,
      lonesomeness, pity or anger. That is, risky and negative emotions were linked to
      social non-acceptance, and not with health problems. Thus, the conclusion is that
      fatness is transmitted from fear and not from a positive construction of the
      health.

PMID- 30208184
TI  - [Internalizing and externalizing behavior problems and substance use in
      adolescence].
AB  - This study investigated the relationship between externalizing behavior problems
      (EBP), internalizing behavior problems (IBP), and combined
      externalizing/internalizing behavior problems (EIBP) in early adolescence (11
      years) and substance use (alcohol, tobacco, and illegal drugs) at 15 years, using
      data from the 1993 Pelotas (Brazil) birth cohort. Behavior problems were assessed
      with the Strengths and Difficulties Questionnaire (SDQ), applied to mothers when
      their children were 15 years old. Substance use was assessed with a self-applied
      confidential questionnaire for the adolescent. The association between behavior
      problems and substance use was analyzed with Poisson regression with robust
      adjustment of variance. After adjusting for confounding, adolescents with EBP
      showed higher risk of alcohol abuse (RR = 1.74, 95%CI: 1.21; 2.50) and
      experimentation (RR = 1.78, 95%CI: 1.42; 2,23) and tobacco use in the previous 30
      days (RR = 2.38, 95%CI: 1.64; 3.45). Adolescents with IBP showed greater risk of
      having tried tobacco (RR = 1.54, 95%CI: 1.22; 1.93) and of having used tobacco
      products in the previous 30 days (RR = 1.92, 95%CI: 1.31; 2.83). Adolescents with
      EIBP showed greater risk of trying (RR = 2.24, 95%CI: 1.57; 3.21) and consuming
      tobacco products in the previous days (RR = 3.01, 95%CI: 1.63; 5.56), and lower
      risk of having tried alcohol at 15 years of age (RR = 0.72, 95%CI: 0.55; 0.94).
      Public health measures aimed at reducing behavior problems in early adolescence
      can help reduce tobacco and alcohol consumption at 15 years.

PMID- 30208185
TI  - [Racial disparity in 10-year breast cancer survival: a mediation analysis using
      potential responses approach].
AB  - The study's objectives were to investigate the association between race/color and
      10-year survival in women with breast cancer and the role of staging as mediator.
      This was a hospital cohort with 481 women with invasive breast cancer diagnosed
      from 2003 to 2005. Comparisons were made between white and black women as to
      sociodemographic characteristics and staging, using the chi-square test, and 10
      year survival, using Kaplan-Meier and Cox regression methods. For the race/color
      variable, direct and indirect effects were estimated, mediated by staging, with
      adjustment for the socioeconomic status of the woman's area of residence and age,
      using the potential responses (counterfactual) model and Cox multiple regression.
      Black women living in low-income census tracts were more likely to use the public
      health care system and to be diagnosed at more advanced stages. Breast cancer
      specific 10-year survival was 64.3% (95%CI: 60.0; 68.9), with a significant
      difference between whites (69.5%; 95%CI: 64.8; 74.6) and blacks (44; 95%CI:
      35.2%; 55.1). In the multivariate models adjusted for income and age, black women
      had worse prognosis (HR = 2.09; 95%CI: 1.76; 2.51), and the proportion mediated
      by staging was 40% (95%CI: 37; 42). There is racial disparity in 10-year breast
      cancer survival in Brazilian women, mediated mainly by more advanced staging at
      diagnosis in black women. This highlights the need to expand both the coverage
      and the quality of breast cancer screening and to facilitate access to early
      diagnosis and treatment in order to reduce racial inequality.

PMID- 30208186
TI  - [Borning in Brazil, an interview with Maria do Carmo Leal].

PMID- 30208187
TI  - Barriers and facilitators to dental care during pregnancy: a systematic review
      and meta-synthesis of qualitative studies.
AB  - Some barriers to dental treatment during pregnancy are poorly understood,
      especially those related to psychosocial factors, which are better explored in
      qualitative studies. The aim of this systematic review was to explore the
      barriers and facilitators to dental care during pregnancy through a thematic
      synthesis of qualitative studies. Qualitative or mixed-methods studies published
      in English, Portuguese, Spanish and French, from 2000 to 2016, were included. The
      search strategies were conducted in PubMed, Scopus, Web of Science, LILACS, BBO
      and CINAHL. To evaluate the quality of the studies, we used the Critical
      Appraisal Skills Programme tool. Thematic synthesis was performed in order to
      interpret and summarize the results. From 2,581 screened studies, ten were
      included in the synthesis. We found 14 analytical themes related to barriers and
      facilitators to dental care during pregnancy that interacted in complex ways:
      physiological conditions, low importance of oral health, negative stigma
      regarding dentistry, fear of/anxiety toward dental treatment, mobility and
      safety, financial barriers, employment, time constraints, social support, lack of
      information, health professionals' barriers, family and friends' advice, beliefs
      and myths about the safety of dental treatment. Myths and beliefs about oral
      health and dental treatment during pregnancy appear to be the most frequent
      barriers, both to pregnant women and to dentists or other health professionals.
      The findings of this review may support new studies, especially to test
      intervention protocols and to guide effective public policies for the promotion
      of oral health during pregnancy.

PMID- 30208188
TI  - Evidence-Based Practice Guideline: Secondary Prevention of Late-Life Suicide.
AB  - Suicide is a tragic, traumatic loss, and one of the most emotionally devastating
      events families, friends, and communities experience. Suicide claims more than
      800,000 lives every year, and some of the highest rates of suicide in the United
      States and globally are among older adults. The purpose of this evidence-based
      guideline is to help health care providers recognize those at risk for suicide
      and recommend appropriate and effective secondary suicide prevention
      interventions. The information in this guideline is intended for health care
      providers who work in a variety of settings, including hospitals, nursing homes,
      rehabilitation centers, out-patient clinics, mental health clinics, home health
      care, and other long-term care facilities. Assessment and preventive treatment
      strategies were derived by exhaustive literature review and synthesis of the
      current evidence on secondary prevention of late-life suicide across practice
      settings. [Journal of Gerontological Nursing, 44(11), 20-32.].

PMID- 30208189
TI  - Motivational Interviewing and Fat Consumption in Older Adults: A Meta-Analysis.
AB  - Diets high in fat increase the risks for obesity and chronic diseases, even for
      older adults, the largest growing population in the United States. In the current
      study, a meta-analysis was performed to examine the effects of motivational
      interviewing (MI) dietary interventions on fat consumption in older adults.
      Electronic databases, journals, and unpublished literature were searched. Six
      primary studies were retrieved, providing seven comparisons between intervention
      and control groups and a total of 1,351 participants. MI had a moderate effect on
      fat intake in older adults (effect size = 0.354, p < 0.01). Studies with
      indicators of higher design quality showed greater MI effects. Nurses and
      providers can incorporate MI into health education and counseling to improve
      older adults' dietary health behaviors. [Journal of Gerontological Nursing,
      44(11), 33-43.].

PMID- 30208191
TI  - Measles in Children.
AB  - Measles, which until recently had been a rare disease in the United States, is re
      emerging in our communities due to a combination of increased global mobility and
      decreased vaccinations across the country. As providers, we need to reacquaint
      ourselves with this disease so that we may diagnose it as well as educate our
      patients on how to prevent it. With public resistance to vaccinations on the
      rise, it is also important to be prepared to answer questions about the measles
      vaccine, its efficacy, and its side effects. By being educated ourselves, we will
      be able to educate our communities and help keep illnesses like measles at bay.
      [Pediatr Ann. 2018;47(9):e340-e344.].

PMID- 30208192
TI  - Infectious Disease Update.

PMID- 30208193
TI  - Evaluation of Prolonged and Recurrent Unexplained Fevers.
AB  - Fever is a common symptom in children. Some children may present to their primary
      care physician with undifferentiated fever; that is, fever for which there is no
      obvious source from the history or physical examination. Undifferentiated fevers
      may be prolonged or recurrent. Distinguishing between the two is helpful for
      narrowing the differential diagnosis, which can be broad and include infections
      and inflammatory diseases and, rarely, malignancies and autoinflammatory
      disorders. The evaluation of such children requires a step-wise approach. Taking
      a detailed history, performing a thorough physical examination, and reviewing a
      fever and symptom diary is crucial in recognizing clues that may ultimately lead
      to a diagnosis. Some children who look good and whose fever disappears may never
      have a diagnosis, whereas referral to a specialist may be prudent for others.
      [Pediatr Ann. 2018;47(9):e347-e353.].

PMID- 30208194
TI  - Antibiotic-Resistant Bacteria and the Use of Novel Antibiotics in Children.
AB  - Infections due to antibiotic-resistant bacteria in children are on the rise
      worldwide. Treating these infections is a challenge for pediatric caregivers. In
      this arms race, the armamentarium of antibiotics is quickly being depleted. This
      article reviews the problems facing clinicians caring for children with resistant
      bacterial infections, examines some of the newer antibiotics, and discusses other
      methods for pediatric caregivers to combat these infections. Only through an
      informed and concerted effort will we be able to address this growing problem in
      children. [Pediatr Ann. 2018;47(9):e354-e358.].

PMID- 30208195
TI  - Clostridium difficile Infection in Children.
AB  - Clostridium difficile is an important cause of health care associated infections.
      The epidemiology of C. difficile infection (CDI) in children has changed over the
      past few decades. There is now a higher incidence in hospitalized children, and
      there has been an emergence of community-onset infection. A hypervirulent strain,
      North American pulse type 1, has also developed. Neonates and young infants have
      high rates of colonization but rarely have symptoms. The well-known risk factor
      for CDI in children age 2 years or older is antibiotic use. Inflammatory bowel
      disease and cancer are associated with increased incidence and severity of CDI.
      Nucleic acid amplification tests are now widely used for diagnosis given their
      rapid turnover and higher sensitivity and specificity. The treatment for an
      initial episode and first recurrence is oral metronidazole. Oral vancomycin is
      reserved for second recurrence or severe cases. A new treatment option, fecal
      bowel transplant, has been reported to be safe and effective in adults, and
      studies are now being conducted in children. [Pediatr Ann. 2018;47(9):e359
      e365.].

PMID- 30208196
TI  - Addressing Vaccine Hesitancy in Clinical Practice.
AB  - Vaccines have had a profound impact on public health; however, parents are
      increasingly refusing or delaying vaccines for their children. Population-based
      studies have demonstrated the safety and efficacy of vaccines. Pediatricians
      should be well informed about vaccine development, safety, and efficacy to
      inspire parental confidence in vaccines. Systemic challenges in discussing and
      providing immunizations exist. Discussions about immunizations may be lengthy and
      time spent discussing immunizations is not routinely reimbursed. Adolescents may
      be inadequately immunized because they do not routinely present for preventive
      health visits. Routine immunizations should be offered and discussed at sick
      visits, particularly for adolescents. Improving immunization rates requires a
      multifaceted approach. [Pediatr Ann. 2018;47(9):e366-e370.].

PMID- 30208197
TI  - Preventing Pediatric Respiratory Syncytial Virus Infection.
AB  - Respiratory syncytial virus (RSV) infection in infants is a major cause of
      morbidity and mortality worldwide. Despite intense research efforts, safe and
      effective vaccines have remained elusive. Risk factors for the development of
      severe disease are well known, and those infants at highest risk are identified
      to receive RSV prophylaxis in the form of anti-RSV monoclonal antibody. Still,
      many other infant groups remain at risk and could benefit from an effective RSV
      prevention program. An explosion of clinic research activity is bringing
      unprecedented progress. Several of the most promising approaches currently being
      evaluated in clinical trials are reviewed. [Pediatr Ann. 2018;47(9):e371-e376.].

PMID- 30208198
TI  - Slipped Capital Femoral Epiphysis: A Review for Pediatricians.
AB  - Slipped capital femoral epiphysis (SCFE) is one of the most common hip
      pathologies that occurs during adolescence, and its incidence has been increasing
      over the past decades. For this reason, pediatricians should be aware of this
      entity to ensure an early diagnosis and intervene in a timely manner. The typical
      patient with SCFE is an adolescent who is obese presenting with hip pain, but it
      can also occur in children who are not obese; therefore, SCFE should be part of
      the differential diagnosis in any skeletally immature patient presenting with hip
      or knee pain. This article provides an overview for the clinician of relevant
      aspects of this disease that can lead to serious long-term consequences if not
      diagnosed and treated appropriately. [Pediatr Ann. 2018;47(9):e377-e380.].

PMID- 30208199
TI  - Influence of preoperative voice assessment on treatment plan prior to airway
      surgery.
AB  - OBJECTIVES/HYPOTHESIS: Voice quality has emerged as an additional long-term
      outcome measure for patients with a history of airway surgery. The goal of this
      study was to evaluate the impact of preoperative voice assessment on the surgical
      management of patients who required complex airway surgery. STUDY DESIGN:
      Retrospective case series. METHODS: We analyzed clinical data for all patients
      who underwent an airway reconstruction procedure from September 1, 2012 to
      September 1, 2017 and had a voice clinic evaluation prior to surgery at a
      tertiary-care pediatric hospital. Each participant underwent a full clinical
      voice evaluation that yielded acoustic, imaging, perceptual, and handicapping
      index data. RESULTS: Six hundred forty-three patients underwent 831 airway
      surgeries (laryngotracheoplasty, cricotracheal resection, slide tracheoplasty,
      laryngeal cleft repair). Ninety-one (14.2%) of the 643 patients underwent a
      formal voice clinic evaluation prior to airway surgery; 39/91 (42.9%) were
      female. The mean age was 10.4 years (95% confidence interval [CI]: 9.2-11.6) with
      31/91 (32.9%) participants demonstrating vocal fold immobility and 33/91 (36.3%)
      vocal fold hypomobility. A voice clinic evaluation provided new information for
      62/91 (68.1%) patients, mainly for laryngeal dynamic components (vocal fold
      motion, source of phonation, arytenoid prolapse) and confirmed suspected
      disorders for the remaining patients. The average baseline Pediatric Voice
      Handicap Index overall score was 38.9 (95% CI: 33.3-44.5), and the average
      overall severity rating of the Consensus Auditory-Perceptual Evaluation of Voice
      was 54 (95% CI: 45.2-62.8). A voice clinic evaluation influenced management of
      56/91 (61.5%) patients either by modification of the surgical plan (26/56, 46%)
      and/or adjusting voice therapy (21/56, 37.5%). CONCLUSIONS: Voice evaluation
      prior to airway reconstruction provided key information that influenced the
      management for most of the patients. Formal voice evaluation should be considered
      prior to complex airway surgery. LEVEL OF EVIDENCE: 4 Laryngoscope, 2018.

PMID- 30208201
TI  - Longitudinal Pure-Tone Threshold Changes in the Same Subjects: Analysis of
      Factors Affecting Hearing.
AB  - OBJECTIVES: To investigate the change of hearing threshold over time and analyze
      factors that could affect hearing, this longitudinal study of pure-tone threshold
      changes in the same subjects at a 9-year interval was performed. STUDY DESIGN:
      Retrospective longitudinal study in a single center (n = 1,978). METHODS: A total
      of 1,978 subjects were included; they received pure-tone audiometry at a 9-year
      interval. The degree of the threshold changes was examined and compared between
      age groups. The subjects' data, such as the level of cholesterol, were analyzed
      to find risk factors on hearing. RESULTS: The average of the threshold changes
      was 3.35 dB in the 20s to 30s; 4.38 dB in the 30s to 40s; 5.75 dB in the 40s to
      50s; 7.21 dB in the 50s to 60s; and 10.00 dB in the 60s to 70s (all P < 0.05). If
      the low-density lipoprotein cholesterol (LDL-C) was maintained below 100 mg/dl,
      the difference in the weighted four-frequency average was 5.45 dB, whereas it was
      6.15 dB in the subjects whose LDL-C was over 100 mg/dl (P = 0.032, age-adjusted).
      In current smokers, the thresholds increased more than in never- or ex-smokers (P
      = 0.026 in the weighted four-frequency average and P = 0.011 at 8,000 Hz, age
      adjusted). CONCLUSION: The degree of the threshold changes exhibited an
      exponential increase with age. Cessation of smoking is advisable to prevent
      increased aggravation of hearing. Strict management of the low-density
      lipoprotein cholesterol may have a positive effect on hearing. LEVEL OF EVIDENCE:
      3. Laryngoscope, 2018.

PMID- 30208200
TI  - Endoscopic Posterior Cricoid Split With Graft in an Adult With Posterior Cricoid
      Fracture.
AB  - A 45-year-old man presented with bilateral vocal fold immobility (BVFI) following
      a remote history of assault. He was found to have a comminuted, telescoped, and
      ossified posterior cricoid fracture on imaging. Electromyography revealed normal
      cricothyroid and thyroarytenoid muscle function, but moderate chronic denervation
      of bilateral posterior cricoarytenoid muscles. The patient underwent endoscopic
      posterior cricoid split with rib graft (EPCS/RG), and he regained moderate vocal
      abduction and full vocal adduction, resolution of dysphonia, and was
      decannulated. This report describes the only case of an adult with BVFI due to a
      posterior cricoid fracture that was successfully treated with EPCS/RG.

PMID- 30208203
TI  - Sudden hearing loss after cialis (tadalafil) use: A unique case of cochlear
      hydrops.
AB  - We discuss a unique case of sudden sensorineural hearing loss after Cialis
      (tadalafil) use, a phosphodiesterase 5 (PDE5) inhibitor, and the implication of
      ipsilateral cochlear hydrops seen on magnetic resonance imaging (MRI). We report
      a case of a 53-year-old male with unilateral low-frequency sudden sensorineural
      hearing loss (SSNHL) after ingestion of tadalafil. The SSNHL occurred 1 day after
      ingestion and was associated with aural fullness and tinnitus. There were no
      symptoms of vertigo. He received oral prednisone immediately after the onset of
      hearing loss without improvement. Delayed intravenous contrast-enhanced three
      dimensional Fluid-attenuated inversion recovery MRI revealed ipsilateral dilation
      of the cochlear duct without any hydronic change in the vestibular system.
      Acetazolamide therapy was initiated, and his symptoms improved. A posttreatment
      audiogram revealed an increase in threshold of 15 dB. To the best of our
      knowledge, this is the first case of cochlear hydrops visualized on imaging after
      a PDE5 inhibitor induced SSNHL. Tadalafil and other PDE5 inhibitors have a known
      association with SSNHL. Despite several proposed mechanisms, there is
      inconclusive evidence of a causal relationship. Our presented case suggests that
      cochlear hydrops may be one possible mechanism of PDE5 inhibitor-associated
      SSNHL. MRI should be considered in the evaluation of such patients who do not
      respond to oral steroids as initial treatment. Laryngoscope, 2615-2618, 2018.

PMID- 30208202
TI  - Histone Variants as Stem Cell Biomarkers for Long-Term Injection Medialization
      Laryngoplasty.
AB  - OBJECTIVES/HYPOTHESIS: Vocal fold (VF) paralysis by sectioning the recurrent
      laryngeal nerve dramatically impacts the life of thyroidectomy patients. Volume
      expanding materials can temporarily restore VF medialization. To prolong this
      benefit, adipose mesenchymal stem cells (ADSCs) and micronized acellular dermis
      (MACD) were co-injected in a rabbit model of injection medialization
      laryngoplasty. Biomarkers of in situ proliferation were identified by mass
      spectrometry proteomics and pathway analysis to guide future efforts to increase
      the length of benefit. METHODS: ADSCs were expanded and/or differentiated into
      chondrocytes (CHON) as collagen microspheres. After VF paralysis rabbits received
      MACD, MACD + undifferentiated ADSC, or MACD+CHON, ADSCs differentiated into
      chondrocytes. After 12 weeks, animals were sacrificed and 5-um paraffin-embedded
      cryosections were prepared from larynges for hematoxylin and eosin visualization
      and nanoflow liquid chromatography electrospray-ionization tandem-mass
      spectrometry analysis of tissue collections. Validated proteins were processed by
      Venn subtraction and gene ontology (GO) overrepresentation analysis to identify
      unique pathways and biomarkers. RESULTS: Confirmed proteins numbered 147 (MACD),
      1,243 (MACD+ADSC), and 1,033 (MACD+CHON). Totally, 333 proteins were uniquely
      found in the MACD+ADSC group, including mesenchymal surface markers CD9, CD44,
      fibronectin, and vimentin. Over 70% of proteins belonged to catalytic activity
      and binding GO categories, with the histone (H) family being overrepresented (P <
      0.05). Histone variants H3.3, H2A.V, and H2A.Z (associated with open chromatin
      states) were overrepresented in the MACD+ADSC group, whereas structural histones
      H2A, H2B, and H4 were not. CONCLUSION: Biomarkers, including atypical histones,
      are associated with in vivo proliferation of ADSCs and an expanded VF
      medialization volume. LEVEL OF EVIDENCE: NA.

PMID- 30208204
TI  - Validity and completeness of the Scandinavian Sarcoma Group Central Register by
      comparison with a nationwide cohort of patients with osteosarcoma in Norway.

PMID- 30208205
TI  - Validity and completeness of the Scandinavian Sarcoma Group Central Register by
      comparison with a nationwide cohort of patients with osteosarcoma in Norway.

PMID- 30208206
TI  - The role of oral oil administration in displaying the chylous tubes and
      preventing chylous leakage in laparoscopic para-aortic lymphadenectomy.
AB  - BACKGROUND AND OBJECTIVES: This study is aimed to investigate the possibility of
      preoperative oral oil administration in displaying the chylous tubes and
      preventing chylous leakage in laparoscopic para-aortic lymphadenectomy. MATERIALS
      AND METHODS: In this retrospective nonrandomized study, of the 30 patients with
      gynecological malignancies who had indications for laparoscopic para-aortic
      lymphadenectomy up to renal vessels, 15 were administered preoperative oral oil
      (oil a administration) (control group) at our hospital between September 2017 and
      June 2018. The chylous tube displaying rates, incidences of chylous leakage, and
      other perioperative data of the two groups were compared. RESULTS: Successful
      display of chylous tubes was observed in 93.3% (14/15) patients in the oil
      administration group. The chylous leakage was zero in the oil administration
      group, and 33.3% (5/15) in the control group. The postoperative drainage duration
      (4.1 +/- 1.0 days vs 7.6 +/- 1.4 days, P = 0.000), somatostatin application time
      (0 day vs 5.9 +/- 0.8 days), and postoperative hospital stay (6.0 +/- 2.3 days vs
      9.1 +/- 2.1 days, P = 0.001) were significantly shorter in the oil administration
      group. The total cost is lower in the oil administration group (4972.52 +/- 80.54
      dollars vs 6260.80 +/- 484.47 dollars, P = 0.000). CONCLUSIONS: Preoperative oil
      administration is a feasible and effective method to display the chylous tubes
      and to prevent the chylous leakage in para-aortic lymphadenectomy.

PMID- 30208207
TI  - The Otolaryngology Match: A Bibliometric Analysis of 222 First-Year Residents.
AB  - OBJECTIVE/HYPOTHESIS: Research has long been acknowledged as important to
      successfully matriculate into an otolaryngology residency position. The objective
      of this study is to perform a bibliometric analysis to quantify the importance of
      scholarly productivity in the otolaryngology match process. STUDY DESIGN:
      Retrospective database review. METHODS: A list of all Accreditation Council for
      Graduate Medical Education-accredited otolaryngology residency programs were
      identified. Websites of programs were reviewed to identify first-year
      otolaryngology residents for the 2016 to 2017 academic year and compared to two
      previous academic years. Research output measures were collected. Residencies
      were tiered 1 to 5 by departmental research output. RESULTS: Two hundred twenty
      two records of first-year otolaryngology residents starting residency in 2016
      were identified. After adjusting for number of total publications, number of
      original research articles, number of review articles, number of case reports,
      number of first author publications, number of otolaryngology-related
      publications, highest journal impact factor, average journal impact factor, and
      years since publication, h-index and number of total publications were associated
      with increasing tier of matriculation based on research output (P < .0001). Only
      number of publications correlated with increasing h-index (B = 1.11). With regard
      to applicant trends, there has been an increase in scholarly productivity as
      measured across all research parameters in the past 3 years. CONCLUSIONS:
      Research is an important component of successfully matriculating into an
      otolaryngology residency program. The h-index is a reliable tool to quantify
      research output and predict the tier of matriculation with regard to
      institutional research output. There has been a steadily increasing level of
      scholarly output among applicants in the past 3 years. LEVEL OF EVIDENCE: NA
      Laryngoscope, 2018.

PMID- 30208208
TI  - Does Delaying Endoscopic Sinus Surgery Adversely Impact Quality-of-Life Outcomes?
AB  - OBJECTIVES: There is little consensus regarding the prognostic value of symptom
      duration in predicting clinical disease severity or quality-of-life (QOL)
      outcomes in patients with chronic rhinosinusitis (CRS). Our objectives were to:
      1) determine if patients with longer symptom duration have worse preoperative
      disease severity and/or QOL, and 2) determine if delayed surgical intervention
      influences outcomes of endoscopic sinus surgery (ESS). METHODS: Patients
      diagnosed with CRS were prospectively enrolled into a multicenter cohort study
      and observed 14.7 (standard deviaton {SD} +/- 4.8) months on average following
      primary ESS. Preoperative symptom duration was stratified into short-term (< 12
      months), middle-term (12-60 months), and long-term (> 60 months). Disease
      severity was assessed using endoscopy and computed tomography. Disease-specific
      QOL was measured with the 22-item Sinonasal Outcome Test (SNOT-22) and
      Rhinosinusitis Disability Index. Adjusted bivariate and multivariate associations
      between symptom duration, disease severity, and QOL scores were evaluated.
      RESULTS: One hundred and thirteen patients met inclusion criteria with 35
      patients lost to postoperative follow-up. No significant differences in
      preoperative disease severity or QOL scores were reported between symptom
      duration subgroups. Participants in the long-term symptom subgroup reported
      significantly greater mean postoperative improvement on SNOT-22 total scores (n =
      28; -36.3[+/- 22.2]) compared to both short-term (n = 27; -23.4[SD +/- 11.3]; P =
      0.039) and middle-term (n = 23; -23.5[SD +/- 20.1]; P = 0.050) subgroups.
      Postoperative QOL improvements in the long-term symptom subgroup remained
      significantly greater (P <= 0.036) after multivariate adjustment. CONCLUSIONS:
      Symptom duration was not associated with mean preoperative disease severity or
      QOL. Patients with long-term symptom duration reported the greatest mean
      postoperative QOL improvement, suggesting that delayed surgical intervention may
      not reduce QOL improvements following ESS. LEVEL OF EVIDENCE: 2c. Laryngoscope,
      2018.

PMID- 30208209
TI  - Does Medical Therapy Improve SinoNasal Outcomes Test-22 Domain Scores? An
      Analysis of Clinically Important Differences.
AB  - OBJECTIVES/HYPOTHESIS: Minimum clinically important differences (MCIDs) for the
      22-item SinoNasal Outcomes Test (SNOT-22) in patients with chronic rhinosinusitis
      (CRS) electing endoscopic sinus surgery (ESS) are well described. However,
      similar estimations for the MCID have not been investigated for patients electing
      continued appropriate medical therapy (CAMT). We sought to determine MCID values
      for a medically treated CRS cohort and compare them to historical MCIDs
      associated with ESS. STUDY DESIGN: Prospective observational cohort study.
      METHODS: One hundred twenty patients with refractory CRS electing CAMT were
      prospectively enrolled from academic referral clinics into an observational
      cohort study. Baseline and posttreatment SNOT-22 survey responses were collected.
      Four distribution-based methods for calculating MCIDs (e.g., half-standard
      deviation, Cohen's d, standard error of measurement, and minimum detectable
      change) were used to identify a range of MCID values for SNOT-22 total and domain
      scores. RESULTS: The average MCID value for SNOT-22 total scores was 8.0, whereas
      mean MCID values for rhinologic, extranasal rhinologic, ear/facial,
      psychological, and sleep symptom domain scores were 3.9, 2.5, 3.3, 3.4, and 2.9,
      respectively, comparable to previously reported values for patients electing ESS.
      Although change in SNOT-22 total scores following CAMT exceeded the MCID, none of
      the average SNOT-22 domain score improvements surpassed their respective MCID
      thresholds. CONCLUSIONS: MCID values for SNOT-22 total and domain scores in
      patients electing CAMT are similar to previously published MCID values associated
      with ESS, indicating that MCID values are independent of treatment modality
      selection. Therefore, despite evidence of statistical significance, CAMT for CRS
      may not be associated with clinically discernable improvements in average SNOT-22
      domain scores. LEVEL OF EVIDENCE: 2c Laryngoscope, 2018.

PMID- 30208210
TI  - Radiation and Second Primary Thyroid Cancer Following Index Head and Neck Cancer.
AB  - OBJECTIVES/HYPOTHESIS: Radiation is thought to increase risk of developing second
      primary thyroid cancer (SPTC). This study estimated the rate of SPTC following
      index head and neck cancer (HNC) and determined whether radiation treatment among
      HNC survivors increased SPTC risk. STUDY DESIGN: Retrospective data analysis.
      METHOD: The Surveillance, Epidemiology, and End Results database (1975-2014) was
      queried for cases of index HNC (N = 127,563) that developed SPTC. Adjusted
      multivariable competing risk proportional hazards model tested risk of developing
      a SPTC following index HNC. Sensitivity analyses using proportional hazards
      models were also performed restricting data to patients who 1) received both
      radiation and chemotherapy and 2) radiation alone. RESULTS: Only 0.2% of index
      HNC survivors (n = 229) developed SPTC, yielding a rate of 26.1 per 100,000
      person-years. For every increasing year of age at diagnosis, patients were 3%
      less likely to develop an SPTC (adjusted hazard ratio [aHR] = 0.97, 95% CI: 0.96
      0.98). Males were also less likely to develop an SPTC (aHR = 0.73, 95% CI: 0.55
      0.96). Radiation (aHR = 0.92, 95% CI: 0.68-1.25), surgery (aHR = 0.79, 95% CI:
      0.56-1.11), and chemotherapy (aHR = 1.13, 95% CI: 0.76-1.69) were not
      significantly associated with developing SPTC. The sensitivity models also did
      not find an association between treatment and risk of SPTC. CONCLUSIONS: Rate of
      developing SPTC following index HNC was very low, and previous exposure to
      radiation did not significantly increase risk in our study population. More
      studies are needed to understand the increasing incidence of thyroid cancer
      across the United States. LEVEL OF EVIDENCE: NA Laryngoscope, 2018.

PMID- 30208211
TI  - Laser Soldering of Cartilage Graft Interposed Into a Tracheal Incision in a
      Porcine Model.
AB  - OBJECTIVES/HYPOTHESIS: Investigate the feasibility of soldering a free cartilage
      graft into a tracheal defect by laser heating and assessing the resulting burst
      pressure and thermal damage to the cartilage. STUDY DESIGN: Animal study.
      METHODS: A 20 * 8 mm defect was created in fresh cadaveric pig tracheas, a
      cartilage graft of the same size was harvested from the thyroid ala cartilage,
      and the graft was fitted into the defect. The soldering process involved covering
      the edges with liquid albumin and using a fiber-laser system for heating the
      edges to temperature T under temperature control. This was done for groups of
      grafts at various temperatures T = 60 degrees C to 90 degrees C. The tracheas
      were sealed, for each group the burst pressure was measured, and a histologic
      examination of the soldered incisions was performed. RESULTS: The burst pressures
      were in the range of 66 to 409 mm Hg. The median burst pressure was 78, 157, 231,
      and 146 mm Hg, respectively, for T = 60 degrees C, 70 degrees C, 80 degrees C,
      and 90 degrees C. Statistical analysis revealed significant differences in burst
      pressures between the T = 60 degrees C group and the T = 80 degrees C and T = 90
      degrees C groups (P < .05). The highest burst pressure was measured in the T = 80
      degrees C group. Histologic examination revealed no thermal damage to the
      cartilage at this temperature. CONCLUSIONS: Performing a sutureless laser
      soldering of a free cartilage graft to a tracheal defect, achieving an immediate
      watertight bond, is feasible. At T = 80 degrees C the highest burst pressures
      were achieved. No histologic damage was observed. In vivo studies are needed
      before implementation of this technique in laryngotracheopasty. LEVEL OF
      EVIDENCE: NA Laryngoscope, 2018.

PMID- 30208212
TI  - Development of a survival animal model for subglottic stenosis.
AB  - OBJECTIVE: To develop a reproducible survival animal model for subglottic
      stenosis. STUDY DESIGN: Prospective study. METHODS: We evaluated five methods of
      inducing airway injury in 30 New Zealand white rabbits to produce a subglottic
      stenosis model. Experimental groups comprised: group 1 (n = 5), which underwent 4
      hour intubation; group 2 (n = 5), which underwent induced subglottic injury with
      a nylon brush; group 3 (n = 10), which underwent subglottic injury with a nylon
      brush, followed by 4-hour intubation; group 4 (n = 5), which underwent subglottic
      injury with Bugbee cautery in 50% of the subglottic circumference, followed by 4
      hour intubation; and group 5 (n = 5), which underwent subglottic injury with
      Bugbee cautery in 75% of the subglottic circumference, followed by 4-hour
      intubation. Five animals were used as controls. Endoscopy of the airway and
      sacrifice of animals were planned at an interval of 14 days postinjury.
      Histologic measurements were analyzed. RESULTS: No animals in groups 1 or 2
      developed stenosis. In group 3, 50% of animals developed symptomatic grade 3
      subglottic and tracheal stenosis, necessitating early endoscopy and sacrifice in
      three animals. Four animals in group 4 developed grade 1 subglottic stenosis, and
      four in group 5 developed grade 2 subglottic stenosis. Histologic measurements of
      lumen areas within each of these two groups were similar; all animals survived
      the follow-up period. CONCLUSION: We successfully developed a reproducible
      survival model for induced subglottic stenosis using a combination of cautery
      induced subglottic injury followed by 4-hour intubation. This model lays the
      foundation for future studies that evaluate endoscopic interventions for the
      management of subglottic stenosis. LEVEL OF EVIDENCE: NA. Laryngoscope, 2018.

PMID- 30208213
TI  - Anatomical Course of the Thyroarytenoid Branch of the Recurrent Laryngeal Nerve.
AB  - OBJECTIVES/HYPOTHESIS: To determine the position and anatomic variability of the
      thyroarytenoid (TA) branch of the recurrent laryngeal nerve (RLN) in an Indian
      population. This study is specifically targeted to aid in identifying the nerve
      for reinnervation procedures for unilateral and bilateral vocal fold paralysis,
      as well as denervation surgeries such as TA myoneurectomy and Selective Laryngeal
      Adductor Denervation and Reinnervation (SLAD-R) for adductor spasmodic dysphonia.
      METHODS: We dissected 46 fresh-frozen adult larynges (92 sides) without
      pathology. A window was created in the thyroid cartilage lamina. The
      intralaryngeal part of the dissection was done using magnification with an ocular
      loupe. The position and direction of the nerve and branching within the cartilage
      window were noted. RESULTS: The TA nerve was found to emerge from the
      posteroinferior quadrant of the cartilage window, irrespective of the dissected
      side (right/left) and gender in all of the 46 larynges. The nerve traveled in an
      oblique direction in 29 specimens (63.04%) and in a vertical direction in 17
      specimens (36.96%). The orientation of the nerve was the same on the two sides of
      the larynx in all of the specimens. Branching was seen within the cartilage
      window in eight larynges (17.39%). CONCLUSIONS: Knowledge of the possible
      variabilities in the course of the TA nerve aids in its localization while
      avoiding trauma to the posterior branch of the RLN that innervates the posterior
      cricoarytenoid and is responsible for vocal fold abduction. LEVEL OF EVIDENCE: NA
      Laryngoscope, 2018.

PMID- 30208214
TI  - Comparing Upper Airway Stimulation to Transoral Robotic Base of Tongue Resection
      for Treatment of Obstructive Sleep Apnea.
AB  - OBJECTIVES: Transoral robotic surgery (TORS) and upper airway stimulation (UAS)
      are modalities for treating tongue base obstruction contributing to obstructive
      sleep apnea (OSA). We aim to compare patients with OSA undergoing TORS to those
      undergoing UAS. METHODS: We retrospectively reviewed patients treated with TORS
      and UAS using the senior authors' surgical database. We evaluated demographic,
      preoperative polysomnography (PSG), postoperative PSG, complication, hospital
      length of stay, and hospital readmission data to compare the two cohorts.
      RESULTS: Seventy-six patients underwent UAS. This included 50 men and 26 women.
      The mean age and body mass index were 61.92 and 29.38. The mean pre- versus
      postoperative apnea hypopnea index (AHI) and O2 nadir were 36.64 versus 7.20 and
      80.27% versus 88.77%, respectfully. The rate of surgical success and
      postoperative AHI less than 15 and 5 were 86.84%, 89.47%, and 59.21. All patients
      underwent ambulatory surgery, and no one was readmitted. Twenty-four patients
      underwent TORS. This included 20 men and four women with a mean age and body mass
      index BMI of 46.42 and 29.63. The mean pre- versus postoperative AHI and O2 nadir
      were 35.70 versus 20.05 and 80.50% versus 84.10%, respectfully. The rate of
      surgical success and postoperative AHI less than 15 and 5 were 54.17%, 50.00%,
      and 20.83%. The mean length of stay was 1.33 days, and four patients were
      readmitted. We found significant differences in age, postoperative AHI and O2
      nadir, surgical success and postoperative AHI less than 15 and 5, length of stay,
      and rate of readmission. CONCLUSIONS: UAS is successful in treating OSA showing
      improved outcomes, length of stay, and readmission compared to TORS. LEVEL OF
      EVIDENCE: 3. Laryngoscope, 2018.

PMID- 30208215
TI  - Facial Palsy-Specific Quality of Life in 920 Patients: Correlation With Clinician
      Graded Severity and Predicting Factors.
AB  - OBJECTIVES: To investigate the correlation between facial palsy severity and
      quality of life in a broad cohort of facial palsy patients and to elucidate
      factors that influence this relationship. STUDY DESIGN: Retrospective study.
      METHODS: Records of patients presenting with a clinician-graded facial function
      (eFACE) and facial palsy-specific quality-of-life patient-reported outcome
      measure (FaCE) scale from the same moment were reviewed. Multiple linear
      regression was performed to study the effect of various variables on FaCE total
      score. RESULTS: A total of 920 of 1,304 patients were included, 59.9% female with
      a mean (standard deviation) age of 48.6 (16.7) years and a median (interquartile
      range palsy duration of 9.6 [2.2; 42.2] months. A multiple linear regression
      model predicting FaCE total score was established, finding 10 significant
      variables: eFACE; viral, malignant, and congenital etiologies; overweight status;
      anxiety; chronic pain; previous treatment; radiotherapy; and duration of palsy
      (R2  = 0.261, P < 0.001). Gender, age, laterality, surgical etiology, depression,
      and timing of evaluation (at initial intake or at follow up) were not found to
      predict FaCE total scores. CONCLUSION: A correlation between facial palsy
      severity and quality of life was found in a large cohort of patients comprising
      various etiologies. Additionally, novel factors that predict quality of life in
      facial palsy were revealed. This information may help specialists to predict
      which facial palsy patients are at higher risk of a poorer quality of life,
      regardless of severity. LEVEL OF EVIDENCE: 4. Laryngoscope, 2018.

PMID- 30208216
TI  - Narrow Band Imaging Endoscopy of the Nasopharynx for Malignancy: An Inter- and
      Intraobserver Study.
AB  - OBJECTIVE: To assess interobserver agreement and intraobserver reproducibility
      when assessing the nasopharynx for malignancy under white light and narrow band
      imaging endoscopy because the decision to biopsy hinges on the examiner's
      perceived chance of malignancy. METHODS: An interobserver and intraobserver
      agreement study utilizing white light and narrow band endoscopic images of the
      nasopharynx. The setting was an academic referral hospital. Participants were 156
      adults with suspected nasopharyngeal carcinoma who underwent white light and
      narrow band imaging endoscopy and biopsy. Images of the nasopharynges were
      subsequently scored for malignancy by four otolaryngologists. The nasopharynx was
      scored on 4-point scales under white light and narrow band imaging endoscopy for
      the likelihood of malignancy or abnormality, respectively. RESULTS: Intraclass
      correlation coefficients for intraobserver agreement for nasopharyngeal
      malignancy for four observers under white light were 0.86, 0.89, 0.79 and 0.88
      (mean 0.855), respectively; and under narrow band imaging they were 0.64, 0.68,
      0.64, and 0.66 (mean 0.655), respectively (all P values < 0.001). The coefficient
      for interobserver reliability under white light was 0.79 (95% confidence interval
      [CI] 0.76-0.82; P < 0.001), which indicated strong agreement. The coefficient for
      interobserver reliability under narrow band imaging was 0.56 (95% CI 0.50-0.61; P
      < 0.001), which indicated moderate agreement. CONCLUSIONS: Intraobserver and
      interobserver agreement for nasopharyngeal malignancy was strong on white light
      endoscopy but only moderate on narrow band imaging endoscopy. Agreement may be
      improved by adopting a standard set of assessment guidelines, including an
      objective detailed morphological analysis under white light and vasculature
      analysis under narrow band imaging. LEVEL OF EVIDENCE: 2a. Laryngoscope, 2018.

PMID- 30208217
TI  - Effect of a Thin Fluid Layer on Surface Wave Speed Measurements: A Lung Phantom
      Study.
AB  - Lung ultrasound (US) surface wave elastography (SWE) is a novel technique that
      measures superficial lung tissue elastic properties. A thin pleural fluid layer
      covers a lung, but its effect on lung measurements in SWE is unknown. We modeled
      a lung and pleural fluid with sponges and a thin layer of US transmission gel.
      Sponge surface wave speeds measured from SWE were compared for sponges without
      and with the thin US gel layer at 3 wave excitation frequencies. The comparison
      showed that the sponge surface wave speed measurements were not affected by the
      thin gel layer.

PMID- 30208218
TI  - Ultrasound Guidance for Implantation of Hypoglossal Nerve Stimulator in a Breast
      Implant Patient.
AB  - The hypoglossal nerve stimulator (HGNS) is an effective treatment for obstructive
      sleep apnea in qualified patients. The implantation is typically performed
      without direct visualization or image guidance. A surgical approach utilizing
      ultrasound guidance has proved useful for patients with silicone breast implants,
      which may be at risk of rupture during insertion of the device. This surgical
      modification expands the population that can benefit from HGNS to now include
      patients with breast implants. Laryngoscope, 2651-2653, 2018.

PMID- 30208219
TI  - Granulomas of the membranous vocal fold after intubation and other airway
      instrumentation.
AB  - OBJECTIVES/HYPOTHESIS: We describe the clinical features of granulomas of the
      membranous vocal fold secondary to endotracheal intubation, bronchoscopy or
      esophagogastroduodenoscopy. STUDY DESIGN: Retrospective case series. METHODS:
      Review of cases at a single tertiary institution with evaluation of patient
      demographic characteristics, time to presentation, time to treatment, and
      clinical outcomes. RESULTS: Thirteen adult patients were identified with
      postintervention granuloma of the membranous vocal fold. All patients were
      female, with a mean age of 60 years (range, 28-81 years). None noted hoarseness
      prior to the intervention, and all noted significant hoarseness postoperatively.
      Conservative treatment with proton pump inhibitors and vocal rest was initially
      implemented in all patients. Four cases resolved without further intervention.
      Nine underwent surgical management because of airway symptoms, failure to
      improve, or patient request. One patient had injury to the contralateral vocal
      fold upon intubation. None experienced recurrence. Five had complete recovery of
      voice postoperatively, four did not. CONCLUSION: Iatrogenic granulomas of the
      membranous vocal fold after intubation or other upper airway instrumentation are
      rare complications presenting in the early postprocedure period with worsening
      hoarseness. Initial conservative treatment may be sufficient to yield resolution,
      and surgical treatment is effective for those failing medical management.
      Permanent voice damage may result from the original injury. LEVEL OF EVIDENCE: 4
      Laryngoscope, 2018.

PMID- 30208220
TI  - ADAMTS13: origins, applications, and prospects.
AB  - ADAMTS13 is an enzyme that acts by cleaving prothrombotic von Willebrand factor
      (VWF) multimers from the vasculature in a highly regulated manner. In pathologic
      states such as thrombotic thrombocytopenic purpura (TTP) and other thrombotic
      microangiopathies (TMAs), VWF can bind to the endothelium and form large
      multimers. As the anchored VWF chains grow, they provide a greater surface area
      to bind circulating platelets (PLTs), generating unique thrombi that characterize
      TTP. This results in microvasculature thrombosis, obstruction of blood flow, and
      ultimately end-organ damage. Initial presentations of TTP usually occur in an
      acute manner, typically developing due to an autoimmune response toward, or less
      commonly a congenital deficiency of, ADAMTS13. Triggers for TMAs that can be
      associated with ADAMTS13 deficiency, including TTP, have been linked to events
      that place a burden on hemostatic regulation, such as major trauma and pregnancy.
      The treatment plan for cases of suspected TTP consists of emergent therapeutic
      plasma exchange that is continued on a daily basis until normalization of PLT
      counts. However, a subset of these patients does not respond favorably to
      standard therapies. These patients necessitate a better understanding of their
      diseases for the advancement of future therapeutic options. Given ADAMTS13's key
      role in the cleavage of VWF and the prevention of PLT-rich thrombi within the
      microvasculature, future treatments may include anti-VWF therapeutics,
      recombinant ADAMTS13 infusions, and ADAMTS13 expression via gene therapy.

PMID- 30208221
TI  - Ultrasound Characteristics of Foot and Ankle Structures in Healthy, Coper, and
      Chronically Unstable Ankles.
AB  - OBJECTIVE: Ankle sprains constitute approximately 85% of all ankle injuries, and
      up to 70% of people experience residual symptoms. While the injury to ligaments
      is well understood, the potential role of other foot and ankle structures has not
      been explored. The objective was to characterize and compare selected ankle
      structures in participants with and without a history of lateral ankle sprain.
      METHODS: A total of 71 participants were divided into 31 healthy, 20 coper, and
      20 chronic ankle instability groups. Ultrasound images of the anterior
      talofibular and calcaneofibular ligaments, fibularis tendons and muscles,
      tibialis posterior, and Achilles tendon were obtained. Thickness, length, and
      cross-sectional areas were measured and compared among groups. RESULTS: When
      under tension, the anterior talofibular ligament (ATFL) was longer in copers and
      chronic ankle instability groups compared to healthy participants (P < .001 and P
      = .001, respectively). The chronic ankle instability group had the thickest ATFL
      and calcaneofibular ligament among the 3 groups (p < 0.001). No significant
      differences (P > .05) in tendons and muscles were observed among the 3 groups.
      CONCLUSIONS: The ultrasound protocol proved reliable and was used to evaluate the
      length, thickness, and cross-sectional areas of selected ankle structures. The
      length of the ATFL and the thickness of the ATFL and calcaneofibular ligament
      were longer and thicker in injured groups compared to healthy.

PMID- 30208222
TI  - Analysis of red blood cell use in elective surgeries over 12 years in Korea.
AB  - BACKGROUND: Red blood cell (RBC) transfusion is a lifesaving process for patients
      with perioperative bleeding, but transfusion can cause adverse events. Effective
      utilization and management of blood products as a limited resource is essential
      when considering cost-efficiency and patient safety. STUDY DESIGN AND METHODS: We
      analyzed the number of RBC units used during the hospitalization of patients who
      had undergone surgical procedures from 2002 to 2013 using National Health
      Insurance Service-National Sample Cohort data, which include a total of 487,238
      cases for 206 selected operations. RESULTS: RBC units were used in 39,637 (8.1%)
      cases. A total of 60,815 RBC units were transfused with a mean of 0.13 units per
      patient overall and a mean of 1.53 units per case receiving RBC transfusion. In
      addition, 56.7% of the RBC units were transfused for females, and 60.1% of RBC
      units were transfused into patients aged 60 or older. RBC units were used most
      often in orthopedic surgeries (33.8%), followed by general surgeries (12.0%) and
      vascular surgeries (11.8%). The number of operations performed in the cohort
      increased from 27,690 in 2002 to 49,473 in 2013, and the mean number of RBC units
      used per operation also increased from 0.08 units in 2002 to 0.15 units in 2013.
      CONCLUSION: Continuous management for blood preparation and transfusion is needed
      for efficient utilization of blood. Periodic investigation on the use of blood
      products through nationwide studies could suggest data applicable to blood
      product preparation for various elective surgical operations.

PMID- 30208224
TI  - Endoscopic Resection Followed by Proton Therapy With Pencil Beam Scanning for
      Skull Base Tumors.
AB  - For patients who require postoperative radiotherapy after endoscopic resection of
      skull base tumors, proton therapy with pencil beam scanning (PBS) may allow
      sparing of normal tissue compared to intensity-modulated photon radiation (IMRT).
      We compared PBS and IMRT radiation plans in the preoperative and postoperative
      settings for two patients with advanced skull base tumors following endoscopic
      resection. The benefits of PBS over IMRT appear greater in the postoperative
      setting following endoscopic resection with improved sparing of critical organs
      at risk. The multidisciplinary approach of endoscopic resection followed by PBS
      represents a treatment paradigm with potential for improvements in toxicity
      reduction.

PMID- 30208223
TI  - Contribution of Fetal Cardiac Axis and V Sign Angle in First-Trimester Screening
      for Major Cardiac Defects.
AB  - OBJECTIVE: To estimate the potential value of fetal assessment for the cardiac
      axis (CAx) and V sign angle (VSA) in the first trimester in the prediction of
      fetal major cardiac defects. METHODS: A cohort study was conducted from December
      2015 to June 2016. Patients with singleton pregnancies and crown rump length from
      45 mm to 84 mm were recruited to undergo nuchal translucency sonography. The CAx
      on the 4-chamber view and the VSA on the 3 vessels and trachea view with Doppler
      mapping were measured. The estimated performance of different combinations of
      increased fetal nuchal translucency, CAx, and VSA in screening for major cardiac
      defects was examined. RESULTS: The study population of fetuses included 30
      fetuses with major cardiac defects and 1538 normal fetuses. The CAx and VSA were
      30 degrees  to 60 degrees  and 30 degrees  to 40 degrees , respectively,
      according to the 2.5th and 97.5th percentiles in normal fetuses. When cases of
      isolated septal wall defects and isolated right aortic arch were excluded, nuchal
      translucency above the 95th percentile, abnormal CAx, or VSA was observed in
      63.3% (19 of 30), 63.3% (19 of 30), 66.7% (20 of 30) of fetuses with major
      cardiac defects, respectively, and in 4.6% (71 of 1538), 2.0% (30 of 1538), and
      5.6% (86 of 1538) of those without cardiac defects. Either abnormal CAx or VSA
      was found in 93.3% (28 of 30) of the fetuses with cardiac defects and in 7.3%
      (113 of 1538) of those without cardiac defects. CONCLUSION: Assessment of CAx and
      VSA is helpful in defining a population at risk for major cardiac defects in the
      first trimester.

PMID- 30208225
TI  - Transoral robotic surgery versus upper airway stimulation in select obstructive
      sleep apnea patients.
AB  - OBJECTIVES: Transoral robotic surgery (TORS) has been used to treat obstructive
      sleep apnea (OSA) since 2009, with recent meta-analysis showing an average
      reduction of apnea-hypopnea index (AHI) from 44.3 to 17.0. In 2014, upper airway
      stimulation surgery (UAS) was approved for OSA treatment, with results showing an
      average AHI reduction from 32.0 to 15.3. Given there was a period when TORS was
      available and UAS was not, we looked at a subset of patients treated with TORS
      but who could have qualified for UAS and compared their outcomes to patients who
      received UAS. METHODS: This is a retrospective chart review comparing TORS to UAS
      in treatment of OSA performed by a single surgeon between 2011 and 2016.
      Inclusion criteria were a body mass index less than 35 and AHI between 20 and 65
      consistent with criteria for UAS implantation. Patients who received TORS and met
      the inclusion criteria had their preoperative drug-induced sleep endoscopy
      recordings re-evaluated. Patients with anteroposterior retropalatal collapse that
      would have qualified them for UAS had their outcomes compared to patients who
      received UAS. RESULTS: Results between TORS and UAS showed an average AHI
      reduction of 12.7 and 33.3, respectively. Overall cure rate, defined as AHI < 5,
      was 10.0% and 70.3%, respectively. CONCLUSION: Results of this study indicate
      that, when met with criteria for both TORS and UAS, patients receiving UAS had
      greater improvement in several objective measures of OSA. Studies like this may
      help direct future treatment algorithms for surgical management of OSA. LEVEL OF
      EVIDENCE: 4. Laryngoscope, 2018.

PMID- 30208226
TI  - Congenital Lobar Overinflation: A Rare Enigmatic Lung Lesion on Prenatal
      Ultrasound and Magnetic Resonance Imaging.
AB  - OBJECTIVES: To report the ultrasound (US) features in prenatal cases of suspected
      congenital pulmonary airway malformation or unspecified lung lesions with a final
      surgical pathologic diagnosis of congenital lobar overinflation (CLO). METHODS:
      Institutional Review Board-approved radiology and clinical database searches from
      2001 to 2017 were performed for prenatally diagnosed lung lesions with a final
      diagnosis of CLO. All patients had detailed US examinations in addition to
      magnetic resonance imaging (MRI). Size, echotexture, and vascularity were
      assessed with US, and the signal and vascularity were assessed with MRI. Follow
      up prenatal US scans, postnatal imaging, and postnatal outcomes were reviewed.
      RESULTS: The study population consisted of 12 patients. The median gestational
      age was 23.3 weeks. The median congenital pulmonary airway malformation volume-to
      head circumference ratio was 0.66. Lesion locations were 6 in the lower lobes (4
      right and 2 left), 5 in the upper lobes (3 left and 2 right), and 1 in the right
      middle lobe. The texture was homogeneously echogenic relative to the normal lung
      in 100% with no visualized macrocysts. Hypervascularity by color Doppler US was
      observed in 5 cases (41.7%). A T2 hyperintense lung lesion was identified by MRI
      in 12 of 12 cases (100%), with elongated vessels identified in 11 of 12 cases
      (91.7%). All 12 cases had pathologically proven CLO. CONCLUSIONS: Congenital
      lobar overinflation should be considered in cases of prenatal echogenic lung
      lesions without macrocysts or classic findings of bronchial atresia.
      Hypervascularity may be an important imaging feature of a subset of CLO. Most
      cases become less conspicuous, decrease in size without overt hydrops, and are
      asymptomatic postnatally.

PMID- 30208227
TI  - Angioleiomyoma of the Extremities: Findings on Ultrasonography and Magnetic
      Resonance Imaging.
AB  - OBJECTIVES: The purpose of this study was to describe the features of
      angioleiomyomas of the extremities on ultrasonography (US) and magnetic resonance
      imaging (MRI). METHODS: We retrospectively reviewed the US and MRI findings of 29
      pathologically confirmed cases of angioleiomyomas of the extremities in 29
      patients. Twenty patients underwent only US; 7 patients underwent only MRI; and 2
      patients underwent US and MRI. Clinical data and histopathologic specimens were
      reviewed. RESULTS: There were 19 women and 10 men. The mean patient age was 48.9
      years (range, 23-80 years). On US, angioleiomyomas were located primarily in the
      subcutaneous fat layer (n = 20 [91%]), were oval (n = 17 [77%]), had well
      circumscribed margins (n = 22 [100%]), had hypoechoic protrusions on one or both
      ends (n = 9 [41%]), had a homogeneous echo texture (n = 17 [ 77%]), had posterior
      acoustic enhancement (n = 20 [91%]), and had color Doppler flow (n = 20 [91%]).
      On MRI, the masses showed heterogeneous enhancement (n = 7 [88%]) and enhancing
      structures on one or both ends (n = 4 [50%]) on contrast-enhanced T1-weighted
      images. CONCLUSIONS: Angioleiomyoma of the extremities is usually a well
      circumscribed oval mass with a homogeneous echo texture and occasionally
      hypoechoic protrusions on US and shows heterogeneous enhancement with
      occasionally enhancing structures on one or both ends of the mass on MRI.
      Therefore, it should be included in the differential diagnosis of a soft tissue
      mass that has protruding structures from one or both ends.

PMID- 30208229
TI  - What Is the Utility of Fine-Needle Aspiration in Parotid Gland Neoplasms?

PMID- 30208228
TI  - Shear Wave Elastography on the Uterine Cervix: Technical Development for the
      Transvaginal Approach.
AB  - OBJECTIVES: This research aimed to identify biological and technical confounders
      in the nonpregnant cervix when applying shear wave elastography with an
      endovaginal transducer. METHODS: Cervical speed measurements were obtained at the
      internal and external os in the anterior and posterior portions of the cervix
      using a transvaginal approach in 69 nongravid patients. RESULTS: Reliable
      measurements were obtained at the external os and internal os, anteriorly and
      posteriorly, in 63, 55, 55, and 26 patients, respectively. The mean speed
      obtained at the external os, anteriorly and posteriorly, was 2.52 +/- 0.49 m/s
      and 2.87 +/- 0.63 m/s, respectively, and at the internal os, anteriorly and
      posteriorly, 3.29 +/- 0.79 m/s and 4.10 +/- 1.11 m/s, respectively. The
      difference in speed between all regions was statistically significant (P < .05).
      CONCLUSION: Ultrasound-induced artifacts appear to affect the transmission of the
      elastographic main pulse, with cervical position contributing to suboptimal shear
      wave production in the posterior cervix. Reliable shear wave propagation can be
      achieved in the anterior cervix in most patients.

PMID- 30208230
TI  - Early Predictors of the Long-term Response to Therapy in Patients With Crohn
      Disease Derived From a Time-Intensity Curve Analysis After Microbubble Contrast
      Agent Injection.
AB  - OBJECTIVES: The aim of this study was to identify early predictors of the long
      term response to therapy in patients with Crohn disease (CD) from time-intensity
      curves obtained after microbubble injection. METHODS: One hundred fifteen
      consecutive patients with a proven diagnosis of CD involving the terminal ileal
      loop who were scheduled to begin pharmacologic therapy with biologics (infliximab
      or adalimumab) were scanned after sulfur hexafluoride-filled microbubble
      injection before the beginning and at the end of the sixth week of treatment. The
      absolute value and percentage change of each semiquantitative kinetic parameter
      (peak enhancement, time to peak enhancement, rise time, mean transit time, wash
      in and wash-out rates, area under the curve [AUC] for the whole time-intensity
      curve, AUC during wash-in, AUC during wash-out, and wash-in perfusion index) as
      measured on the terminal ileal tract and adjacent reactive mesenteric fat were
      calculated from time-intensity curves. Patients were followed for at least 24
      months with redetermination of the Crohn Disease Activity Index and with at least
      1 endoscopy within 18 weeks after the beginning of pharmacologic treatment. The
      absolute values and percentage changes of kinetic parameters were assessed as
      potential predictors of the therapeutic outcome by a logistic regression
      analysis. RESULTS: The study group included 66 male and 49 female patients (mean
      age +/- SD, 45.76 +/- 11 years). The pretreatment values and percentage changes
      of the peak enhancement, AUC, AUC during wash-in, and AUC during wash-out were
      found to be predictors (P < .05) of the long-term therapeutic outcome.
      CONCLUSIONS: The analysis of time-intensity curves obtained after microbubble
      contrast agent injection provides early predictors of the long-term therapeutic
      outcome in patients with CD.

PMID- 30208231
TI  - Cerebral and Extracerebral Vasoreactivity in Patients With Different Clinical
      Manifestations of Cerebral Small-Vessel Disease: Data From the Significance of
      Hemodynamic and Hemostatic Factors in the Course of Different Manifestations of
      Cerebral Small-Vessel Disease Study.
AB  - OBJECTIVES: Endothelial dysfunction has been implicated in the pathogenesis of
      cerebral small-vessel disease (SVD). Little is known about the relationship
      between SVD and measures of endothelium-dependent vasodilatation and cerebral
      vasomotor reactivity. The aim of this study was to evaluate cerebral and
      extracerebral endothelial dysfunction in patients with different manifestations
      of SVD and to assess the relationship between endothelial dysfunction and
      radiologic markers of SVD. METHODS: The vasomotor reactivity reserve (VMRr),
      breath-holding index (BHI) of the middle cerebral arteries, and brachial artery
      flow-mediated dilatation (FMD) were measured with ultrasound techniques in 90
      patients (30 in each group) older than 60 years with extensive white matter
      lesions (Fazekas grade >= 2) with a history of lacunar stroke, vascular dementia,
      or parkinsonism and 30 individuals with normal magnetic resonance imaging
      findings (control group). All groups were matched for age, sex, hypertension, and
      diabetes. RESULTS: The mean age +/- SD (71.8 +/- 3.4 versus 71.7 +/- 3.4 years),
      sex distribution, and prevalence of the main vascular risk factors were similar
      in the SVD and control groups. The VMRr (56.6% +/- 18.3% versus 77.1% +/- 16.9%),
      BHI (0.8 +/- 0.3 versus 1.1 +/- 0.4), and FMD (5.8% +/- 4 versus 12.1% +/- 5.2%)
      were severely impaired in the SVD groups compared to the control group (P < .01).
      The vascular responses to all tests was similar in the SVD groups, but they were
      significantly decreased in patients with severe white matter lesions, marked
      brain atrophy, and enlarged perivascular spaces. CONCLUSIONS: This study was the
      first that simultaneously evaluated cerebral and extracerebral vasodilator
      responses in a well-phenotyped cohort of patients with lacunar stroke, vascular
      dementia, or parkinsonism. The VMRr, BHI, and FMD were more severely impaired in
      patients with SVD, regardless of its clinical manifestation, than in control
      participants. All measures were significantly lower in patients with severe white
      matter lesions, brain atrophy, or enlarged perivascular spaces.

PMID- 30208232
TI  - Ultrasonography Technique in Abdominal Subcutaneous Adipose Tissue Measurement: A
      Systematic Review.
AB  - There are currently several reported techniques of sonographic subcutaneous
      adipose tissue (SAT) measurement described in the literature. This systematic
      review aims to report techniques of SAT measurement using ultrasonography. A
      systematic literature search was performed and identified 39 relevant articles
      using ultrasonography to quantify abdominal SAT. The following parameters were
      collected: type of measurement, ultrasound machine make/model, transducer
      frequency, external/internal landmarks, pressure applied on probe, special
      techniques and inter-/intraobserver reliability. Literature findings related to
      the above parameters were summarized. A summary of the most common techniques and
      parameters is provided, serving as a reference for a necessary standardized
      approach.

PMID- 30208233
TI  - Z Score Reference Ranges of Fetal Cardiothoracic Diameter Ratio.
AB  - OBJECTIVE: This study aims to establish the z score reference ranges of
      cardiothoracic diameter ratio (CTR) of normal fetuses from 14 to 40 weeks'
      gestation. METHOD: A cross-sectional study was conducted on low-risk singleton
      pregnancies with healthy fetuses. The CTR was performed using simple 2
      dimensional sonography on the typical fetal 4-chamber view. The reference ranges
      were constructed according to gestational age (GA), biparietal diameter (BPD),
      and head circumference (HC) as independent variables based on the best-fit
      models, both mean and standard deviation (SD). RESULTS: A total of 683 fetuses
      were measured for CTR. The best-fit equations for the mean and SD as a function
      of GA, BPD, and HC are as follows: (1) CTR = 0.365 + 0.004 * GA in weeks (SD =
      0.031 + 0.001 * GA); (2) CTR = 0.373 + 0.014 * BPD in cm (SD = 0.034 + 0.004 *
      BPD); and (3) CTR = 0.373 + 0.004 * HC in cm (SD = 0.032 + 0.001 * HC). The CTR
      was slightly increased with advanced GA, BPD, and HC. CONCLUSION: Complete
      nomograms with z score reference ranges of CTR were established throughout
      pregnancy. These nomograms may be useful to detect cardiac abnormalities.

PMID- 30208235
TI  - Can Constrictive Pericarditis Be Life-Saving?

PMID- 30208236
TI  - The Reliability of Suprapatellar Transverse Sonographic Assessment of Femoral
      Trochlear Cartilage Thickness in Healthy Adults.
AB  - OBJECTIVES: To determine the intrasession reliability of femoral cartilage
      thickness measurements using sonography and extend the pool of normative data for
      cartilage thickness measurements assessed by sonography. METHODS: A total of 77
      healthy participants (55 men, 22 women), with an average age of 43 +/- 18 (mean
      +/- standard deviation) years, volunteered. Resting suprapatellar sonography was
      used to image trochlear cartilage thickness on 2 separate occasions a maximum of
      7 days apart. Reliability was evaluated with intraclass correlation coefficients,
      Bland-Altman analysis, standard error of measurement, and the smallest real
      difference. Normative data was assessed using linear, multiple regression models
      and independent group t tests. RESULTS: The test-retest level of agreement at all
      locations was high (intraclass correlation coefficient, 0.779-0.843), which
      increased to high-very high in young adults (intraclass correlation coefficient,
      0.884-0.920). The standard error of measurement was 8.2% to 8.3% at all locations
      and reduced further to 5.4% to 6.3% in younger adults. The smallest real
      difference was between 22.8% and 23.1% for the full sample and 14.9% and 17.5% in
      young adults only. Multiple regression analyses demonstrated that age, weight,
      female sex, and a high physical activity frequency could significantly predict
      cartilage thickness at all locations (P < .05); however, female sex was the only
      significant independent predictor in all models (all P < .01). Females also had
      thinner cartilage at all locations (P < .01). CONCLUSION: Suprapatellar
      sonography demonstrates high intratester reliability and measurement precision
      and is a promising method to assess trochlear cartilage thickness. Being female
      may impact femoral cartilage thickness more than other potential risk factors for
      knee osteoarthritis such as age, weight, and high physical activity frequency.

PMID- 30208234
TI  - A Multicenter Large-Sample Shear Wave Ultrasound Elastographic Study of the
      Achilles Tendon in Chinese Adults.
AB  - OBJECTIVES: The changes in the viscoelasticity of the Achilles tendon are related
      to tendinopathy. Therefore, constructing a data model in the healthy population
      is essential to understanding the key factors affecting the viscoelasticity of
      the Achilles tendon. The purpose of our research was to obtain large sample data,
      construct a data model, and determine parameters that affect the elastic modulus
      of the Achilles tendon in healthy Chinese adults. METHODS: We designed a
      prospective multicenter clinical trial to evaluate the viscoelasticity of the
      Achilles tendon by using shear wave elastography. A total of 1165 healthy adult
      participants from 17 Chinese hospitals were recruited for the assessment. The
      necessary parameters (age, height, weight, and body mass index) were recorded.
      The elastic modulus (Young modulus) was obtained from the middle of the Achilles
      tendon and calculated with feet in naturally relaxed, dorsal, and plantar
      positions. The thickness and perimeter of the Achilles tendon were measured via
      cross section on the same site. A multiple linear regression was performed to
      find the key factors affecting the Young modulus of the Achilles tendon. RESULTS:
      The Young modulus of the left Achilles tendon in the natural relaxed position
      followed a normal distribution (P > .05) with a mean +/- SD of 374.24 +/- 106.12
      kPa. The regression equations showed a positive correlation between the Young
      modulus and weight and a negative correlation between the Young modulus and the
      circumference or thickness of the left Achilles tendon (P < .05). CONCLUSIONS:
      The Young modulus of the Achilles tendon as measured by shear wave elastography
      is related to body weight as well as the perimeter or thickness of the tendon.

PMID- 30208237
TI  - Endoscopic resection of a chorda tympani schwannoma: A novel approach for an
      exceedingly rare entity.
AB  - We present a novel approach for a rare chorda tympani schwannoma. A case report
      as well as special considerations in all phases of care are reviewed.
      Laryngoscope, 2018.

PMID- 30208238
TI  - Speckle Tracking of the Basal Lateral and Septal Wall Annular Plane Systolic
      Excursion of the Right and Left Ventricles of the Fetal Heart.
AB  - OBJECTIVE: Annular plane systolic excursion (APSE) has been evaluated for the
      right (RV) and left (LV) ventricles using M-mode echocardiography. This study
      examined APSE using 2-dimensional speckle tracking (2DST) of the lateral and
      septal annuli of the RV and LV in normal fetuses. METHODS: Two hundred normal
      fetuses were prospectively examined between 20 and 40 weeks' gestation, in which
      the end-diastolic and end-systolic lengths were measured from the apex to the
      insertion of the annuli into the lateral and septal walls of the RV and LV using
      2DST. Subtracting the end-systolic from the end-diastolic length resulted in the
      APSE measurement. The APSE values from the ventricular and septal locations were
      regressed against biometric and gestational age independent variables, and the
      mean and standard deviation computed using fractional polynomial analysis. Within
      subject repeated measures of variance were used to compare results within and
      between the right ventricular and left ventricular basal APSE values. RESULTS:
      When regressed against the independent variables the R2 for the APSE of the right
      ventricular lateral wall ranged from 0.39 to 0.40, the left ventricular lateral
      wall 0.29 to 0.31, the right ventricular septal wall 0.22 to 0.40, and the left
      ventricular septal wall 0.05 to 0.07. There was a significant difference (P <
      .001) for APSE between the right ventricular and left ventricular lateral wall
      and their respective septal annuli, the left ventricular and right ventricular
      lateral wall annuli, and the left ventricular and right ventricular septal
      annuli. CONCLUSIONS: The right ventricular and left ventricular lateral and
      septal wall APSE can be computed using 2DST and are associated with changing
      fetal biometric and age measurements.

PMID- 30208239
TI  - Trends in Medical Claims and Utilization of Limited Ultrasonography Among
      Emergency Physicians and Radiologists Within a Large Health Plan Provider.
AB  - OBJECTIVES: The goal of this study was to evaluate trends in medical claim
      submissions for limited ultrasound studies performed (1) during emergency
      department (ED) encounters and (2) by ED providers compared to radiologists.
      METHODS: We conducted a retrospective, descriptive study using medical claims
      data from Medica Health Plans from January 1, 2011 to December 31, 2015. Current
      procedural terminology codes were abstracted for limited ultrasound applications
      performed during an ED visit and further stratified by studies performed by ED
      providers compared with radiologists. We excluded claims for which we could not
      determine provider specialty. RESULTS: We identified 42,576 encounters with
      limited US claims, of which, 32,666 were submitted by ED providers (N = 9649) or
      radiologists (N = 23,017). Among ED providers, there was a significant linear
      increase in the annual number of claims for retroperitoneal (P < .001) and
      nonlinear increases for thoracic, soft tissue, cardiac, transvaginal
      genitourinary (GU) and transabdominal GU claims (all P < .001). Compared with
      radiologists, there was a linear increase in the annual proportion of claims
      submitted for retroperitoneal (P = .023), transabdominal GU (P = .003), and
      transvaginal GU (P < .001) studies by ED providers. There was a nonlinear
      decrease in the annual proportion of limited abdomen claims (P < .001) submitted
      by ED providers compared with radiologists. CONCLUSIONS: Using data from a large
      health plan provider, we show that medical claims for many limited ultrasound
      studies are increasing among ED providers. Compared with radiologists, ED
      providers are increasingly submitting claims for retroperitoneal, soft tissue,
      and transabdominal GU studies.

PMID- 30208241
TI  - Optimal Timing of Spinal Ultrasound Evaluations for Sacral Dimples in Neonates:
      Earlier May Not Be Better.
AB  - OBJECTIVES: A spinal ultrasound (US) evaluation during the immediate postnatal
      period may have limited ability in evaluating filum thickness because of the
      spinal cord pulsation caused by a crowded subarachnoid space and the
      cerebrospinal fluid deficiency during this period. This study aimed to determine
      the optimal timing of spinal US to evaluate sacral dimples in neonates. METHODS:
      This study included 585 neonates who had a clinically suspicious sacral dimple
      and underwent spinal US examinations between January 2015 and August 2017.
      Patients were classified into 1 of 2 groups based on whether measurements of all
      parameters were possible (group A) or not (group B). Neonatal and maternal
      clinical factors, including the antenatal history and US parameters, were
      compared between groups. RESULTS: Group A included 443 patients, and group B
      included 82. Patients in group B were significantly younger (6.2 versus 31.0
      days), had a younger corrective age (38.9 versus 42.5 weeks), and had a smaller
      body weight (3.1 versus 4.6 kg) than those in group A (all P < .005). However, no
      statistically significant differences were found in other patient or maternal
      factors (P > .05 for all). The pulsation of the conus medullaris and nerve roots
      of the cauda equina (14.6% versus 100%), thickening and echogenicity of the filum
      terminale (2.4% versus 100%), and the presence of a normal subarachnoid space
      (18.3% versus 100%) were significantly more difficult to detect in group B than
      in group A (all P < .001). CONCLUSIONS: For an accurate evaluation, which can
      reduce unnecessary confusion and costs, spinal US can be delayed until neonates
      grow beyond 31 days, with a corrected age of older than 42.5 weeks and body
      weight of greater than 4.6 kg.

PMID- 30208240
TI  - Diagnostic Value of Arrival Time Parametric Imaging Using Contrast-Enhanced
      Ultrasonography in Superficial Enlarged Lymph Nodes.
AB  - OBJECTIVE: The aim of this study was to evaluate the value of arrival-time
      parametric imaging for differential diagnosis of superficial enlarged lymph
      nodes. METHODS: Patients with lymphadenopathy who received contrast-enhanced
      ultrasonography (CEUS) and biopsy were included in this study. Following CEUS, a
      prototype software of the arrival-time parametric imaging system was used to
      analyze the video footage. Arrival-time patterns during the arterial phase were
      evaluated. The quantitative parameters including arrival time of periphery,
      arrival time of center, and the travel time (?T) were calculated. RESULTS: A
      total of 145 lymph nodes were analyzed. Arrival-time parametric imaging showed
      that 80.3% of metastatic lymph nodes and 68.4% of lymphoid tuberculosis presented
      a centripetal perfusion pattern, 76.5% of lymphoma showed complete homogeneous
      enhancement, and 81.2% of reactive lymph nodes had centrifugal patterns. The
      arrival time of periphery (sec) of metastatic lymph nodes was substantially
      earlier than that of lymphoma (11.0 +/- 3.1 versus 12.6 +/- 3.6; P < .05). The
      arrival time of center (sec) of metastatic lymph nodes was obviously later than
      that of lymphoma and reactive lymph nodes (13.4 +/- 3.3 versus 10.5 +/- 2.9 and
      10.6 +/- 1.5; P < .05). The travel time (?T) (sec) in metastatic lymph nodes was
      substantially longer than in reactive lymph nodes and lymphoma (4.2 +/- 2.1
      versus 2.3 +/- 1.6 and 2.9 +/- 2.5; P < .05). At a ?T cutoff value of 2.75
      seconds (using the receiver operating characteristic curve), the sensitivity and
      specificity in differentiating metastatic lymph nodes from benign lymph nodes
      (lymphoid tuberculosis and reactive lymph nodes) were 78.9% and 64.7%,
      respectively. CONCLUSIONS: Enhanced patterns and parameters of arrival-time
      parametric imaging during CEUS could provide more information for the
      differential diagnosis of enlarged superficial lymph nodes.

PMID- 30208242
TI  - A Novel Ultrasound-Guided Technique for Hysteroscopic Adhesiolysis in High-Risk
      Patients.
AB  - Hysteroscopy is a common gynecologic surgical procedure. Certain diagnoses,
      notably intrauterine adhesions and cervical stenosis, make hysteroscopy more
      complicated because of an increased likelihood of complications. Three patients,
      1 with cervical stenosis and 2 with Asherman syndrome, underwent ultrasound (US)
      guided adhesiolysis. Access to the uterine cavity was obtained by either direct
      balloon-aided dilation or the US-guided Seldinger technique, followed by balloon
      aided dilation to enter the endometrial cavity and disrupt
      intrauterine/intracervical adhesions. In this case series, we describe a novel
      approach of using US-guided balloon dilation to safely and effectively treat
      intrauterine adhesions and to decrease the risk of perforation.

PMID- 30208243
TI  - The Use of Ultrasound Simulators to Strengthen Scanning Skills in Medical
      Students: A Randomized Controlled Trial.
AB  - OBJECTIVES: This study evaluates the use of ultrasound simulators for retaining
      and improving ultrasound skills acquired in undergraduate ultrasound training.
      METHODS: Fourth-year medical students (n = 19) with prior training in point-of
      care sonography for shock assessment were recruited for this study. Students were
      randomly assigned to a study group (n = 10) that followed an undergraduate
      ultrasound training curriculum, then used a simulator to complete 2 self-directed
      practice ultrasound sessions over 4 weeks. The control group (n = 9) followed the
      same undergraduate ultrasound training curriculum and received no additional
      access to a simulator or ultrasound training. A blinded assessment of the
      students was performed before and after the 4-week study period to evaluate their
      image acquisition skills on standardized patients (practical examination). To
      evaluate the student's clinical understanding of pathological ultrasound images,
      students watched short videos of prerecorded ultrasound scans and were asked to
      complete a 22-point questionnaire to identify their findings (visual
      examination). RESULTS: All results were adjusted to pretest performance. The
      students in the study group performed better than those in the control group on
      the visual examination (80.1% versus 58.9%; P = .003) and on the practical
      examination (77.7% versus 57.0%; P = .105) after the 4-week study period. The
      score difference on the postintervention practical examinations was significantly
      better for the study group compared to the control group (11.6% versus -9.9%; P =
      .0007). CONCLUSION: The use of ultrasound simulators may be a useful tool to help
      previously trained medical students retain and improve point-of-care ultrasound
      skills and knowledge.

PMID- 30208244
TI  - Accessible Personal Ultrasound Training Simulator.
AB  - OBJECTIVES: Ultrasound simulators are increasingly used for teaching and training
      purposes, but development has been limited by the need for dedicated and often
      expensive hardware. The objective of this study was to develop and deploy an
      accessible and very low-cost personal ultrasound training simulator and obtain
      trainee feedback. METHODS: An ultrasound simulator software program that uses a
      smartphone as a "mock-probe" and a laptop computer as a "mock ultrasound machine"
      was created. Spatial positional data is acquired from the smartphone's inbuilt
      accelerometer and gyroscope and transmitted to the laptop computer for processing
      and display of simulated ultrasound images in real time by the software program.
      After obtaining institutional review board approval and informed consent, all
      first-year radiology residents at our institution were provided access to the
      simulator program during the "bootcamp" introductory conference series, and a
      written survey was conducted to obtain feedback. RESULTS: A personal ultrasound
      training simulator software program (Persimus) that reliably performs motion
      sensing along 2 axes and displays simulated ultrasound images was developed. Nine
      of 12 (75%) first-year residents at our institution participated in the written
      survey. Residents' scored values were 8.44 +/- 1.33 and 8.44 +/- 1.33 (mean +
      standard deviation) for perceived utility and overall impression and
      satisfaction, respectively, of the simulator on the Likert scale (1-10, with 10
      being the highest score). CONCLUSION: Personal ultrasound simulators are
      technically feasible. These are well received by first-year radiology residents
      and perceived as useful to their education.

PMID- 30208246
TI  - Calcaneal Broadband Ultrasound Attenuation and Speed of Sound Measurements in a
      Population of Nigerian Children: Reference Data and the Influence of
      Sociodemographic Variables.
AB  - OBJECTIVES: The aim of our study was to establish a reference database of
      calcaneal broadband ultrasound attenuation (BUA) and the speed of sound (SOS) in
      a healthy Nigerian population of children aged 6 to 14 years and also to
      investigate the influence of sociodemographic and anthropometric variables on
      them. METHODS: The BUA and SOS of 1016 healthy children were measured by
      quantitative ultrasound densitometry. Height and weight were measured with a
      stadiometer and weighing balance, respectively, whereas the sociodemographic
      parameters of the participants were collected on a semistructured questionnaire.
      A multiple regression model using stepwise selection and Pearson correlation
      coefficients were used to examine the relationship between the ultrasound
      parameters and sociodemographic and anthropometric parameters. Comparisons
      between various age groups were made by analysis of variance. RESULTS: The mean
      BUA and SOS +/- SD of the participants were 60.57 +/- 16.21 dB/MHz and 1563.48 +/
      21.74 m/s, respectively, for boys and 58.18 +/- 15.16 dB/MHz and 1560.03 +/-
      22.32 m/s for girls. The BUA in both sexes was positively influenced by age and
      weight (P < .05), whereas only the father's educational status was its predictor
      (P < .05) in the boys. For the girls, the family size and mother's educational
      status were predictors of the BUA (P < .05). The SOS was marginally influenced by
      age and family size in the boys (P < .05), whereas the father's educational
      status was the predictor in the girls. CONCLUSIONS: The established BUA and SOS
      values in this study are baseline values, and further study, which would also
      involve data from a large number of Nigerian children, would be needed to support
      their effectiveness as reference values.

PMID- 30208245
TI  - Variability in radiation dose and image quality: A comparison across fluoroscopy
      system vendors, generations of equipment and institutions.
AB  - OBJECTIVES: To evaluate differences in radiation dose and image quality across
      institutions, fluoroscope vendors and generations of fluoroscopes for pediatric
      cardiac catheterization. BACKGROUND: Increased recognition of the potentially
      harmful effects of ionizing radiation has spurred technological advances in
      fluoroscopes, as well as increased focus on optimizing fluoroscope performance.
      There is currently little understanding of variability in the dose-image quality
      relationship across institutions, fluoroscope vendor and/or generation of
      equipment. METHODS: We evaluated latest generation fluoroscopes from Phillips,
      Siemens, GE, and Toshiba, and an older generation Phillips fluoroscope (release
      date 2003) at three different institutions. Radiation dose was measured using an
      anthropomorphic dose-assessment phantom with effective dose in mSv estimated from
      Monte Carlo simulations. Image quality phantom images were scored on a 12-point
      scale by three blinded reviewers. RESULTS: Fluoroscope effective doses ranged
      from 0.04 to 0.14 mSv/1,000 pulses for fluoroscopy with associated composite
      image quality scores ranging from 8.0 +/- 0.6 to 10.4 +/- 1.3. For
      cineangiography, effective doses ranged from 0.17 to 0.57 mSv/1,000 frames with
      image quality scores ranging from 10.1 +/- 0.3 to 11.1 +/- 0.3. There was modest
      correlation between effective dose and image quality (r = 0.67, P = 0.006). The
      older generation fluoroscope delivered consistently higher doses than the newer
      generation systems (2.3- to 3.5-fold higher for fluoroscopy; 1.1- to 3.4-fold
      higher for cineangiography) without appreciable differences in image quality.
      CONCLUSION: Technological advances have markedly improved fluoroscope
      performance. Comparing latest generation systems across vendors and institutions,
      we found variability in the dose-IQ relationship and speculate that this reflects
      both equipment and institutional optimization practices.

PMID- 30208248
TI  - New Method for Assessment of Levator Avulsion Injury: A Comparative Elastography
      Study.
AB  - OBJECTIVE: The aim of this study was to introduce elastography as a new method
      for sonographic assessment of postpartum pelvic floor trauma. METHODS: We
      examined 86 postpartum primiparous women, of whom 43 had undergone primary
      caesarean section (group_CS) and 43 vaginal delivery (group_VD). In a puborectal
      symphysis plane, B-mode and elastographic ultrasonography were used to evaluate
      pelvic floor trauma. The strain value of left and right puborectal muscle was
      assessed close to the symphysis (Trauma_Elastography). The strain ratio maximum
      of this measurement was stored (Trauma_Index). RESULTS: The elastographic
      evaluation revealed more trauma-suspicious lesions than the B-mode investigation
      (60.5% versus 39.5%; P < .001). The median Trauma_Index was higher in group_VD
      compared to group_CS (1.63 versus 1.18; P < .001). CONCLUSION: Sonographic
      elastography assessment in a new examination plane shows postpartum trauma of the
      pelvic floor in women after vaginal delivery. This new method may help to
      identify women with a higher risk of postpartum pelvic floor disorders.

PMID- 30208247
TI  - Cryptotanshinone (Dsh-003) from Salvia miltiorrhiza Bunge inhibits prostaglandin
      E2-induced survival and invasion effects in HA22T hepatocellular carcinoma cells.
AB  - Human hepatocellular carcinoma (HCC) is currently the second most common cancer
      and one of the leading causes of cancer-related mortality in Taiwan. Previous
      reports show that the expression of (E-type prostaglandin 2) EP2 and (E-type
      prostaglandin 4) EP4 are elevated in HCC and further demonstrate that
      Prostaglandin E2 (PGE2) induces HA22T cell proliferation and metastasis through
      EP2 and EP4 receptor. Danshen (root of Salvia miltiorrhiza Bunge) is a very
      important and popular traditional Chinese herbal medicine which is widely and
      successfully used against breast cancer, leukemia, pancreatic cancer, and head
      and neck squamous carcinoma cells. In this study, we used Cryptotansinone (Dsh
      003) (MW 269.14) from Danshen to investigate their effect and corresponding
      mechanism of action in PGE2-treated HA22T cells. Dsh-003 inhibited HA22T cell
      viability and further induced cell apoptosis in PGE2-treated HA22T cells.
      Furthermore, Dsh-003 inhibited EP2, EP4, and their downstream effector such as p
      PI3K and p-Akt expression in HA22T hepatocellular carcinoma cells. We also
      observed that Dsh-003 blocked PGE2-induced cell migration by down-regulating PGE2
      induced beta-catenin expression and by up-regulating E-cadherin and GSK3-beta
      expression. All these findings suggest that Dsh-003 inhibit human HCC cell lines
      and could potentially be used as a novel drug for HCC treatment.

PMID- 30208249
TI  - Off-label use of duct occluder devices to close hemodynamically significant
      perimembranous ventricular septal defects: A multicenter experience.
AB  - OBJECTIVE: We sought to evaluate the feasibility, technical aspects, and outcome
      of transcatheter perimembranous ventricular septal defect (pmVSD) closure using
      duct occluder devices with a single retention disc. BACKGROUND: Use of duct
      occluder devices to close pmVSD seems a promising alternative therapy. However,
      limited data exist on this technique. METHODS: From 2010 to 2016, 222 patients
      (female 47.7%) were identified from databases of five participating institutions
      in whom pmVSD closure was attempted using an Amplatzer Duct Occluder I or
      Lifetech duct occluder device. RESULTS: Patients ranged in age from 0.7 to 52
      years (median, 7.0 years) and in weight from 4.0 to 70 kg (median, 18.0 kg). The
      mean size of the VSD was 6.8 +/- 2.2 mm. A large defect (> 6 mm) was present in
      137 patients (61.7%). Device closure was successful in 218 patients (98.2%). The
      10/8 mm device was used in most patients (n = 85, 38.3%), and the vascular
      approach was from the femoral vein in 169 patients (76.1%). There were 18 early
      complications in 17/218 patients (7.8%). Three patients (1.4%) developed complete
      heart block (transient n = 2; requiring permanent pacing n = 1). Median follow-up
      was 6 months (6 months-6 years). A mild residual shunt was seen in 10 patients at
      6 months follow-up. CONCLUSIONS: The immediate results of transcatheter pmVSD
      closure using a duct occluder device with a single retention disc are promising.
      It is an effective technique with a lower rate of complications than for other
      currently available devices.

PMID- 30208250
TI  - Acute myocardial infarction secondary to blunt chest trauma in motorcycle
      accident: A rare combination where percutaneous coronary intervention and
      intravascular imaging optimization are needed.
AB  - Blunt chest trauma is a common occurrence in vehicle accident. Cardiac injuries
      following nonpenetrating thoracic trauma have been reported. ST-elevation
      myocardial infarction (STEMI) due to coronary artery involvement is a rare but
      extremely serious condition for the high risk of undetected diagnosis. Blunt
      thoracic trauma may obscure typical chest pain associated with cardiac ischemia
      especially in patients with high tolerance of pain or secondary administration of
      analgesic drugs. We report two consecutive cases of young adults admitted to our
      emergency department after motorcycle accident and concomitant anterior STEMI due
      to occlusion of left anterior descending artery. In both cases primary
      percutaneous coronary intervention with a second generation drug eluting stent
      implantation was successfully performed. Imaging with intravascular ultrasound
      and optical coherence tomography showed the mechanisms of coronary occlusion,
      allowing an optimal stent implantation and avoiding procedural complications in
      this complex setting.

PMID- 30208251
TI  - Breakdown of Curly Arrow Rules in Anthraquinone.
AB  - Understanding and controlling quantum interference (QI) in single molecules is
      fundamental to the development of QI-based single-molecule electronics. Simple
      rules such as counting rules, curly arrow rules (CARs), circuit rules, and more
      recently magic ratio rules have been developed to predict QI patterns in
      polycyclic aromatic hydrocarbons. CARs are widely used to predict destructive QI.
      Here we examine the validity of CARs in fully conjugated anthracene and
      dihydroxyanthracene, cross-conjugated anthraquinone, and broken conjugated
      dihydroanthracene attached to either graphene or gold electrodes through pi-pi
      stacking or thiol and Au-C anchors. For the first time, we demonstrate that CARs
      break down in molecular junctions formed by cross-conjugated anthraquinone. In
      contrast with the destructive QI predicted by CARs for a meta-connected
      anthraquinone core, we demonstrate that QI is constructive. This behavior is
      independent of the choice of electrode material or anchor groups. This is
      significant, because by changing the redox state of meta-connected
      dihydroxyanthracene to form meta-connected anthraquinone, the conductance of the
      junction increases by a couple of orders of magnitude due to the crossover from
      constructive to destructive QI. This opens new avenues for realization of QI
      based single-molecule switches.

PMID- 30208252
TI  - The TAM receptor TYRO3 is a critical regulator of myelin thickness in the central
      nervous system.
AB  - Multiple sclerosis (MS) is an autoimmune, demyelinating disease of the central
      nervous system (CNS). Major deficits arise in MS patients due to an inability to
      repair damaged myelin sheaths following CNS insult, resulting in prolonged axonal
      exposure and neurodegeneration. The TAM receptors (Tyro3, Axl, and Mertk) have
      been implicated in MS susceptibility, demyelination and remyelination.
      Previously, we have shown that Tyro3 regulates developmental myelination and
      myelin thickness within the optic nerve and rostral region of the corpus callosum
      (CC) of adult mice. In this study we have verified and extended our previous
      findings via a comprehensive analysis of axonal ensheathment and myelin thickness
      in the CC of unchallenged mice, following demyelination and during myelin repair.
      We show that the loss of the Tyro3 receptor correlates with significantly thinner
      myelin sheaths in both unchallenged mice and during remyelination, particularly
      in larger caliber axons. The hypomyelinated phenotype observed in the absence of
      Tyro3 occurs independently of any influence upon oligodendrocyte precursor cell
      (OPC) maturation, or density of oligodendrocytes (OLs) or microglia. Rather, the
      primary effect of Tyro3 is upon the radial expansion of myelin. The loss of Tyro3
      leads to a reduction in the number of myelin lamellae on axons, and is therefore
      most likely a key component of the regulatory mechanism by which oligodendrocytes
      match myelin production to axonal diameter.

PMID- 30208253
TI  - NBCe1 mediates the regulation of the NADH/NAD+ redox state in cortical astrocytes
      by neuronal signals.
AB  - Astrocytes are a glial cell type, which is indispensable for brain energy
      metabolism. Within cells, the NADH/NAD+ redox state is a crucial node in
      metabolism connecting catabolic pathways to oxidative phosphorylation and ATP
      production in mitochondria. To characterize the dynamics of the intracellular
      NADH/NAD+ redox state in cortical astrocytes Peredox, a genetically encoded
      sensor for the NADH/NAD+ redox state, was expressed in cultured cortical
      astrocytes as well as in cortical astrocytes in acutely isolated brain slices.
      Calibration of the sensor in cultured astrocytes revealed a mean basal cytosolic
      NADH/NAD+ redox ratio of about 0.01; however, with a broad distribution and
      heterogeneity in the cell population, which was mirrored by a heterogeneous basal
      cellular concentration of lactate. Inhibition of glucose uptake decreased the
      NADH/NAD+ redox state while inhibition of lactate dehydrogenase or of lactate
      release resulted in an increase in the NADH/NAD+ redox ratio. Furthermore, the
      NADH/NAD+ redox state was regulated by the extracellular concentration of K+ ,
      and application of the neurotransmitters ATP or glutamate increased the NADH/NAD+
      redox state dependent on purinergic receptors and glutamate uptake, respectively.
      This regulation by K+ , ATP, and glutamate involved NBCe1 mediated sodium
      bicarbonate transport. These results demonstrate that the NADH/NAD+ redox state
      in astrocytes is a metabolic node regulated by neuronal signals reflecting
      physiological activity, most likely contributing to adjust astrocytic metabolism
      to energy demand of the brain.

PMID- 30208254
TI  - Prognostic impact of baseline and residual SYNTAX scores in cardiogenic shock.
AB  - OBJECTIVES: The aim was to assess the extent of coronary artery disease and
      revascularization using baseline SYNTAX Score (bSS) and residual SYNTAX Score
      (rSS) in patients with cardiogenic shock (CS) secondary to ST-segment elevation
      myocardial infarction (STEMI). The prognostic impact of SYNTAX Score (SS) was
      evaluated and assessed for additive value over clinical risk scores. BACKGROUND:
      bSS and rSS have been proven to be useful in risk stratification in stable
      coronary artery disease as well as in acute coronary syndromes, but they have not
      been studied in STEMI related CS. METHODS: Patients from a multinational
      prospective study of CS were analyzed. The study population was divided into
      tertiles according to bSS. The Cox regression and receiver operating
      characteristic (ROC) curves were used to assess the predictive power of SS.
      RESULTS: Of the 61 studied patients, 85% were male and the mean age was 67 years.
      Median bSS was 22 (15-32) and rSS 7 (0-13). Ninety-day mortality was 43%. bSS had
      negative prognostic value in multivariable analysis (HR 1.06, 95% CI 1.01-1.10).
      However, additive value over clinical risk scores was limited. rSS was not
      associated with mortality, whereas post-percutaneous coronary intervention (PCI)
      TIMI flow 3 of infarct-related artery (IRA) predicted better survival.
      CONCLUSIONS: In STEMI related CS, the added value of bSS and rSS over clinical
      assessment and risk scores is limited. Our results suggest that while immediate
      PCI in order to restore blood flow to the IRA is essential, deferring the
      treatment of residual lesions does not seem to be associated with worse
      prognosis.

PMID- 30208255
TI  - Collagen organization deposited by fibroblasts encapsulated in pH responsive
      methacrylated alginate hydrogels.
AB  - The pH of dermal wounds shifts from neutral during the inflammatory phase to
      slightly basic in the tissue remodeling phase. Stage specific wound treatment can
      be developed using environmentally responsive alginate hydrogels. The chemistry
      of these networks dictates swelling behavior. Here, we fabricated alginate
      hydrogels using chain growth, step growth, and combined mixed mode gelation
      methods to crosslink methacrylated alginate (ALGMA) and gain control over
      swelling responses. Methacrylation of the alginate network was confirmed through
      NMR spectroscopy. Strontium cations were introduced to fabricate stiffer, dually
      crosslinked hydrogels. Dual crosslinking significantly decreased the swelling
      response over the pH range of 3-9 for step growth and chain growth hydrogels,
      with no impact on mixed mode hydrogels. The extent of crosslinking altered the
      hydrogel degradation profiles under accelerated degradation conditions.
      Encapsulated NIH/3T3 fibroblasts in the different ALGMA hydrogels remained viable
      with greater cell proliferation in the stiffer gels. Collagen organization
      deposited by the NIH/3T3 fibroblasts was monitored using second harmonic
      generation (SHG) microscopy and was influenced by the crosslinking mechanism.
      Ionic chain growth and ionic mixed mode crosslinked ALGMA hydrogels caused
      relatively isotropic collagen organization, particularly 10 days post-cell
      encapsulation. Principal component analysis (PCA) was employed to uncover
      correlations between the observed properties. The ability of these
      environmentally responsive gels to induce isotropic collagen and respond to pH
      changes means they hold promise as phase specific wound dressings. (c) 2018 Wiley
      Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2934-2943, 2018.

PMID- 30208257
TI  - Bioactive composites based on double network approach with tailored mechanical,
      physico-chemical, and biological features.
AB  - Hyaluronic acid (HA)-based hydrogels are one of the most promising naturally
      derived biomaterials for tissue engineering applications, as they can play an
      important role in many key cellular processes. In this study, HA was chemically
      functionalized with photo-cross-linkable motifs by reacting with methacrylic
      anhydride (MA) to obtain methacrylated hyaluronic acid (MeHA). A range of MA/HA
      molar ratios was used to obtain different degrees of substitution (DS) ranging
      from 3.5% to 74.5%, as showed by nuclear magnetic resonance and attenuated total
      reflection spectroscopy. By fine tuning the DS, the chemical reaction parameters,
      and the polymer concentration, it was demonstrated the possibility to tailor
      their mechanical features. Double network (DN) hydrogels were prepared through
      the synergic use of MeHA and polyethylene glycole diacrylate (PEGDA). To improve
      the biological properties of DN hydrogels, bioactive solid signals such as
      hydroxyapatite nanoparticles (HAp) prepared by sol-gel approach were used in
      combination with DN hydrogels to obtain an advanced composite material with dual
      function in terms of mechanical and biological support for soft/hard tissue
      formation. The results highlighted that composite-DN hydrogels showed a 10-time
      increase of the storage modulus, if compared to neat MeHA, and an early alkaline
      phosphatase expression from human mesenchymal stem cells in basal medium. This
      work can be considered a first systematic approach for the designing of photo
      cross-linkable hydrogels, based on a combination of natural/synthetic polymers
      and HAp, that could be applied in three-dimensional additive manufacturing
      techniques such as stereolithography. (c) 2018 Wiley Periodicals, Inc. J Biomed
      Mater Res Part A: 106A: 3079-3089, 2018.

PMID- 30208258
TI  - Retrograde percutaneous coronary intervention for acute myocardial infarction
      following blunt chest trauma.
AB  - A 78-year-old man was admitted to the emergency department because of chest pain
      following blunt chest trauma. Chest X-ray revealed multiple rib fractures.
      However, electrocardiogram showed ST elevation in inferior leads suggesting acute
      myocardial infarction (AMI). Emergency coronary angiography revealed normal left
      coronary artery and occluded proximal right coronary artery. Thus, percutaneous
      coronary intervention (PCI) was performed immediately. Antegrade PCI was
      unsuccessful due to a very large false lumen, which was caused by a blunt trauma.
      However, retrograde guidewire (GW) manipulation was relatively easy to negotiate
      the occluded lesion. After GW externalization, we deployed two drug eluting
      stents for this lesion. To our knowledge, this is the first case of retrograde
      PCI that led to a successful reperfusion therapy for AMI following blunt chest
      trauma.

PMID- 30208256
TI  - Decreased BOLD fluctuations in lateral temporal cortices of premature born
      adults.
AB  - Lasting volume reductions in subcortical and temporal-insular cortices after
      premature birth suggest altered ongoing activity in these areas. We hypothesized
      altered fluctuations in ongoing neural excitability and activity, as measured by
      slowly fluctuating blood oxygenation of resting-state functional MRI (rs-fMRI),
      in premature born adults, with altered fluctuations being linked with underlying
      brain volume reductions. To investigate this hypothesis, 94 very preterm/very low
      birth weight (VP/VLBW) and 92 full-term born young adults underwent structural
      and rs-fMRI data acquisition with voxel-based morphometry and amplitude of low
      frequency fluctuations (ALFF) as main outcome measure. In VP/VLBW adults, ALFF
      was reduced in lateral temporal cortices, and this reduction was positively
      associated with lower birth weight. Regions of reduced ALFF overlapped with
      reduced brain volume. On the one hand, ALFF reduction remained after controlling
      for volume loss, supporting the functional nature of ALFF reductions. On the
      other hand, ALFF decreases were positively associated with underlying brain
      volume loss, indicating a relation between structural and functional changes.
      Furthermore, within the VP/VLBW group, reduced ALFF was associated with reduced
      IQ, indicating the behavioral relevance of ALFF decreases in temporal cortices.
      These results demonstrate long-term impact of premature birth on ongoing BOLD
      fluctuations in lateral temporal cortices, which are linked with brain volume
      reductions. Data suggest permanently reduced fluctuations in ongoing neural
      excitability and activity in structurally altered lateral temporal cortices after
      premature birth.

PMID- 30208259
TI  - Biomarkers of disseminated intravascular coagulation in pediatric intensive care
      unit in Thailand.
AB  - INTRODUCTION: Disseminated intravascular coagulation (DIC) is a systemic
      activation of hemostatic system caused by several causes. Biomarkers including
      antithrombin (AT), protein C (PC), and thrombomodulin (TM) were reported as the
      additional markers for DIC in adults. This study aimed to determine the
      association between biomarkers among patients with overt DIC (ODIC) and nonovert
      DIC (NDIC) in children in PICU. METHODS: We enrolled 103 subjects, aged 1 month
      18 years, who were admitted to PICU at Chiang Mai University (CMU) Hospital >24
      hours with underlying conditions predisposing to DIC were enrolled. Biomarkers
      were tested after 24 hours of admission. Subject who had NDIC on the 1st
      investigations would have other tests on days 3-5 of admission. RESULTS: The
      incidence of ODIC by the International Society on Thrombosis and Hemostasis
      (ISTH) DIC score was found 24%. The bleeding, thrombosis, and death were
      significantly higher in ODIC group (P < 0.05). Mean levels of AT and PC in ODIC
      group were significantly different from NDIC one (66.9% vs 79.9%, P < 0.001 and
      46.1% vs 59.2%, P = 0.004, respectively) while mean level of TM was not different
      between two groups. Adding AT to DIC score was better than the original score for
      predict mortality [area under curve (AUC) = 0.662 vs AUC = 0.65] and bleeding
      (AUC = 0.751 vs AUC = 0.732). CONCLUSIONS: ODIC is prevalent among critically ill
      children. Adverse outcomes were more commonly found in children with ODIC. AT and
      PC levels after 24 hours of PICU admission seem to be the useful biomarkers for
      ODIC in PICU.

PMID- 30208260
TI  - A 3D in vitro model of the dermoepidermal junction amenable to mechanical
      testing.
AB  - Recessive dystrophic Epidermolysis Bullosa (RDEB) is caused by mutations in
      collagen-type VII gene critical for the dermoepidermal junction (DEJ) formation.
      Neither tissues of animal models nor currently available in vitro models are
      amenable to the quantitative assessment of mechanical adhesion between dermal and
      epidermal layers. Here, we created a 3D in vitro DEJ model using extracellular
      matrix (ECM) proteins of the DEJ anchored to a poly(ethylene glycol)-based slab
      (termed ECM composites) and seeded with human keratinocytes and dermal
      fibroblasts. Keratinocytes and fibroblasts of healthy individuals were well
      maintained in the ECM composite and showed the expression of collagen type VII
      over a 2-week period. The ECM composites with healthy keratinocytes and
      fibroblasts exhibited yield stress associated with the separation of the model
      DEJ at 0.268 +/- 0.057 kPa. When we benchmarked this measure of adhesive strength
      with that of the model DEJ fabricated with cells of individuals with RDEB, the
      yield stress was significantly lower (0.153 +/- 0.064 kPa) consistent with our
      current mechanistic understanding of RDEB. In summary, a 3D in vitro model DEJ
      was developed for quantification of mechanical adhesion between epidermal- and
      dermal-mimicking layers, which can be utilized for assessment of mechanical
      adhesion of the model DEJ applicable for Epidermolysis Bullosa-associated
      therapeutics. (c) 2018 The Authors. Journal Of Biomedical Materials Research Part
      A Published By Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 3231
      3238, 2018.

PMID- 30208261
TI  - Cardiac structure and function before and after bariatric surgery: a clinical
      overview.
AB  - Obesity, defined as a body mass index of >=30 kg/m2 , is the most common chronic
      metabolic disease worldwide and its prevalence has been strongly increasing.
      Obesity has deleterious effects on cardiac function. The purpose of this review
      is to evaluate the effects of obesity and excessive weight loss due to bariatric
      surgery on cardiac function, structural changes and haemodynamic responses of
      both the left and right ventricle.

PMID- 30208262
TI  - Unusual BK polyomavirus-associated urologic malignancies in renal transplant
      recipients: Report of two cases and review of the literature.
AB  - Renal transplant recipients are at increased risk of developing urologic
      malignancies, some of which are associated with prolonged BK virus infection. We
      report two cases of BK virus-associated carcinoma with variant morphological
      patterns (clear cell adenocarcinoma of the bladder and micropapillary urothelial
      carcinoma of the pelvicaliceal system) arising in the urinary tract of renal
      transplant recipients. In both cases, the diagnosis was initially established on
      cytologic specimens: on urine cytology in one patient and on fine needle
      aspiration of an inguinal lymph node in the other patient. The unusual cytologic
      features of both cases (multiple morphologies in one patient and micropapillary
      pattern in the other), co-occurrence of decoy cells in the urine of one patient
      and the occurrence of these tumors in renal transplant recipients raised the
      possibility of BK polyomavirus-associated malignancy and led to confirmatory SV40
      immunostains that were positive. These cases expand the morphologic variants of
      BK virus-associated urologic malignancies diagnosed in solid organ transplant
      patients. While differentiating BK virus-infected cells from malignant cells in
      urine cytology specimens is a diagnostic challenge, greater awareness of their
      possible co-existence is vital, as this could be the only chance for an early
      diagnosis.

PMID- 30208263
TI  - CT determined psoas muscle area predicts mortality in women undergoing
      transcatheter aortic valve implantation.
AB  - OBJECTIVES: The aim of this study was to assess the predictive value of PMA
      measurement for mortality. BACKGROUND: Current surgical risk stratification have
      limited predictive value in the transcatheter aortic valve implantation (TAVI)
      population. In TAVI workup, a CT scan is routinely performed but body composition
      is not analyzed. Psoas muscle area (PMA) reflects a patient's global muscle mass
      and accordingly PMA might serve as a quantifiable frailty measure. METHODS: Multi
      slice computed tomography scans (between 2010 and 2016) of 583 consecutive TAVI
      patients were reviewed. Patients were divided into equal sex-specific tertiles
      (low, mid, and high) according to an indexed PMA. Hazard ratios (HR) and their
      confidence intervals (CI) were determined for cardiac and all-cause mortality
      after TAVI. RESULTS: Low iPMA was associated with cardiac and all-cause mortality
      in females. One-year adjusted cardiac mortality HR in females for mid-iPMA and
      high-iPMA were 0.14 [95%CI, 0.05-0.45] and 0.40 [95%CI, 0.15-0.97], respectively.
      Similar effects were observed for 30-day and 2-years cardiac and all-cause
      mortality. In females, adding iPMA to surgical risk scores improved the
      predictive value for 1-year mortality. C-statistics changed from 0.63 [CI = 0.54
      0.73] to 0.67 [CI: 0.58-0.75] for EuroSCORE II and from 0.67 [CI: 0.59-0.77] to
      0.72 [CI: 0.63-0.80] for STS-PROM. CONCLUSIONS: Particularly in females, low iPMA
      is independently associated with an higher all-cause and cardiac mortality.
      Prospective studies should confirm whether PMA or other body composition
      parameters should be extracted automatically from CT-scans to include in clinical
      decision making and outcome prediction for TAVI.

PMID- 30208264
TI  - A Call to Action for Optimizing the Electronic Health Record in the Parenteral
      Nutrition Workflow: Executive Summary.
AB  - Parenteral nutrition (PN) is a complex therapeutic modality provided to neonates,
      children, and adults for various indications. Surveys have shown that current
      electronic health record (EHR) systems are in need of functionality enhancement
      for safe and optimal delivery of PN. This is a consensus statement from the
      American Society for Parenteral and Enteral Nutrition, the Academy of Nutrition
      and Dietetics, and the American Society of Health-System Pharmacists outlining
      some of the key challenges to prescribing, order review/verification,
      compounding, and administration of PN using EHRs today and is a call to action
      for clinicians and vendors to optimize their EHRs regarding the PN build and
      workflow.

PMID- 30208265
TI  - Editor's Note.

PMID- 30208266
TI  - A review of systematic reviews on the effects of patient-reported outcome
      monitoring with clinical feedback systems on health-related quality of life
      implications for a novel technology in obesity treatment.
AB  - Patient-reported outcome monitoring with clinical feedback systems (PRO/CFS) has
      been employed in many disease states to measure and improve health-related
      quality of life (HRQOL). Exploring the role of PRO/CFS in treatment for obesity
      may prove valuable. Systematic reviews were summarized to determine the
      effectiveness of PRO/CFS on HRQOL in any disease area. Primary studies evaluating
      the effect of PRO/CFS on HRQOL in treatment for obesity were also considered for
      inclusion. Systematic searches were performed in The Cochrane Library, PROSPERO,
      Epistemonikos, HTA, DARE, CINAHL, Medline, Embase, PsycINFO, BMJ Clinical
      Evidence, PDQ-Evidence and PubPsych. Two reviewers independently screened
      references until final inclusion and critically appraised included reviews using
      PRISMA checklist. Five systematic reviews and no primary studies met inclusion
      criteria. Although results were inconsistent, effectiveness of PRO/CFS on HRQOL
      was demonstrated in some diseases/treatments (e.g. psychiatric treatment; symptom
      burden in cancer treatment). No trials using PRO/CFS in treatment for obesity
      were identified. In some trials, PRO/CFS was not fully integrated into
      consultations, thereby PRO/CFS was not extensively studied. General effectiveness
      of PRO/CFS on HRQOL is inconclusive due to heterogeneous and statistically
      insignificant findings, and lack of stringency in conceptualization and execution
      of PRO/CFS. There are no data relevant to treatment for obesity. Future studies
      should use rigorous methodology to examine the effectiveness of PRO/CFS in
      treatment for obesity.

PMID- 30208267
TI  - Protocol for Chromatin Immunoprecipitation of Meiotic-Stage-Specific Tomato
      Anthers.
AB  - Interactions occurring between DNA and proteins across the nuclear genome
      regulate numerous processes, including meiosis. Meiosis ensures genetic variation
      and balanced segregation of homologous chromosomes. It involves complex DNA
      protein interactions across the entire genome to regulate a broad range of
      processes, including formation and repair of double-strand DNA breaks (DSBs),
      chromosome compaction, homolog pairing, synapsis, and homologous recombination.
      The latter meiotic event, meiotic recombination, often occurs at discrete
      locations in a genome, within a tight time window. The identification of genomic
      binding sites of meiotic proteins is a major step toward understanding the
      molecular mechanisms underlying meiotic recombination and provides important
      information for plant breeding. Collecting meiotic cells from plants is
      challenging, tedious, and time consuming, since the meiocyte-producing organs,
      the anthers, are generally small and limited to certain developmental stages of
      plants. Here we provide a protocol to isolate meiotic-stage-specific anthers and
      perform ChIP on this material. We have developed a ChIP protocol specifically
      suited to (1) small amounts of input material and (2) proteins that bind
      transiently to chromatin and at very low frequency. (c) 2018 by John Wiley &
      Sons, Inc.

PMID- 30208268
TI  - Five Types of People in Organizational Change: Experience shows that change,
      especially culture change, happens best from within.

PMID- 30208269
TI  - 25 Indicators of Ergonomic Progress: Tangible and sustaining improvements are
      built in three stages.

PMID- 30208270
TI  - Oxidation of the Cyanobactin Precursor Peptide Is Independent of the Leader
      Peptide and Operates in a Defined Order.
AB  - The five-membered nitrogen plus heteroatom rings known as azolines or in their
      oxidized form as azoles are very common in natural products and drugs. The
      oxidation of thiazoline to thiazole in the cyanobactin class of natural products
      is one of the several important transformations that are known to alter the
      biological properties of the compound. The ordering of the various chemical
      reactions that occur during cyanobactin biosynthesis is not fully understood. The
      structure of the flavin-dependent enzyme responsible for the oxidation of
      multiple thiazolines reveals it contains an additional domain that in other
      enzymes recognizes linear peptides. We characterize the activity of the enzyme on
      two substrates: one with a peptide leader and one without. Kinetics and
      biophysics reveal that the leader on the substrate is not recognized by the
      enzyme. The enzyme is faster on either substrate than the macrocyclase or
      protease in vitro. The enzyme has a preferred order of oxidation of multiple
      thiazolines in the same linear peptide.

PMID- 30208271
TI  - The Zinc Linchpin Motif in the DNA Repair Glycosylase MUTYH: Identifying the Zn2+
      Ligands and Roles in Damage Recognition and Repair.
AB  - The DNA base excision repair (BER) glycosylase MUTYH prevents DNA mutations by
      catalyzing adenine (A) excision from inappropriately formed 8-oxoguanine (8
      oxoG):A mismatches. The importance of this mutation suppression activity in tumor
      suppressor genes is underscored by the association of inherited variants of MUTYH
      with colorectal polyposis in a hereditary colorectal cancer syndrome known as
      MUTYH-associated polyposis, or MAP. Many of the MAP variants encompass amino acid
      changes that occur at positions surrounding the two-metal cofactor-binding sites
      of MUTYH. One of these cofactors, found in nearly all MUTYH orthologs, is a [4Fe
      4S]2+ cluster coordinated by four Cys residues located in the N-terminal
      catalytic domain. We recently uncovered a second functionally relevant metal
      cofactor site present only in higher eukaryotic MUTYH orthologs: a Zn2+ ion
      coordinated by three Cys residues located within the extended interdomain
      connector (IDC) region of MUTYH that connects the N-terminal adenine excision and
      C-terminal 8-oxoG recognition domains. In this work, we identified a candidate
      for the fourth Zn2+ coordinating ligand using a combination of bioinformatics and
      computational modeling. In addition, using in vitro enzyme activity assays,
      fluorescence polarization DNA binding assays, circular dichroism spectroscopy,
      and cell-based rifampicin resistance assays, the functional impact of reduced
      Zn2+ chelation was evaluated. Taken together, these results illustrate the
      critical role that the "Zn2+ linchpin motif" plays in MUTYH repair activity by
      providing for proper engagement of the functional domains on the 8-oxoG:A
      mismatch required for base excision catalysis. The functional importance of the
      Zn2+ linchpin also suggests that adjacent MAP variants or exposure to
      environmental chemicals may compromise Zn2+ coordination, and ability of MUTYH to
      prevent disease.

PMID- 30208272
TI  - Chemical Proteomics and Super-resolution Imaging Reveal That Chloroquine
      Interacts with Plasmodium falciparum Multidrug Resistance-Associated Protein and
      Lipids.
AB  - It is well established that chloroquine, a quinoline antimalarial, inhibits
      hemozoin formation in the malaria parasite. Counterintuitively, this archetypal
      antimalarial is also used in the treatment of diseases in which hemozoin
      biocrystallization does not play a role. Hence, we decided to investigate whether
      chloroquine possesses binding targets other than Fe(III) protoporphyrin IX in
      blood stage Plasmodium falciparum parasites and whether these are related to
      sites of accumulation within the parasite other than the digestive vacuole. A 7
      nitrobenz-2-oxa-1,3-diazole (NBD)-labeled fluorescent derivative of chloroquine,
      especially sensitive to regions outside the digestive vacuole and retaining the
      antiplasmodial pharmacophore, was synthesized to investigate subcellular
      localization in the parasite. Super-resolution microscopy revealed association
      with membranes including the parasite plasma membrane, the endoplasmic reticulum,
      and possibly also the mitochondrion. A drug-labeled affinity matrix was then
      prepared to capture protein binding targets of chloroquine. SDS-PAGE revealed a
      single prominent band between 200 and 250 kDa from the membrane-associated
      fraction. Subsequent proteomic analysis revealed that this band corresponded to
      P. falciparum multidrug resistance-associated protein (PfMRP1). Intrigued by this
      finding, we demonstrated pull-down of PfMRP1 by matrices labeled with Cinchona
      alkaloids quinine and quinidine. While PfMRP1 has been implicated in resistance
      to quinolines and other antimalarials, this is the first time that these drugs
      have been found to bind directly to this protein. Based on previous reports,
      PfMRP1, the only prominent protein found to bind to quinolines in this work, is
      likely to modulate the activity of these antimalarials in P. falciparum rather
      than act as a drug target.

PMID- 30208273
TI  - Perspectives of Informed Citizen Panel on Low-Carbon Electricity Portfolios in
      Switzerland and Longer-Term Evaluation of Informational Materials.
AB  - Low-carbon transition is gaining momentum, but relatively little is known about
      the public preferences for low- and zero-carbon electricity portfolios given
      their environmental, health, and economic impacts. Decision science literature
      argues that conventional opinion surveys are limited for making strategic
      decisions because the elicited opinions may be distorted by misconceptions and
      awareness gaps that prevail in the public. We created an informed citizen panel (
      N = 46) in Switzerland using technology factsheets, interactive web-tool
      Riskmeter, and group discussions. We measured the evolution of the panel's
      knowledge and preferences from initial (uninformed) to informed and longer-term
      views 4 weeks after. In terms of energy transition, our elicited technology and
      portfolio preferences show strong support for the low-carbon electricity sector
      transition, especially relying on hydropower, solar power, electricity savings
      and efficiency, and other renewable sources. Since these informed preferences are
      structurally different from the futures considered by many energy experts, we
      argue that these preferences should also inform the Swiss Energy Strategy 2050s
      implementation. In terms of methodologies in decision science, our factsheets,
      Riskmeter, and group discussions all proved effective in forming the preferences
      and improving knowledge. But we also intriguingly found that in a longer run the
      participants tended to revert back to their initial opinions. The latter finding
      opens up multiple new research questions on the longer-term effectiveness of
      informational tools and stability of informed preferences.

PMID- 30208274
TI  - Vibrational Control of Covalency Effects Related to the Active Sites of
      Molybdenum Enzymes.
AB  - A multitechnique spectroscopic and theoretical study of the
      Cp2M(benzenedithiolato) (M = Ti, V, Mo; Cp = eta5-C5H5) series provides deep
      insight into dithiolene electronic structure contributions to electron transfer
      reactivity and reduction potential modulation in pyranopterin molybdenum enzymes.
      This work explains the magnitude of the dithiolene folding distortion and the
      concomitant changes in metal-ligand covalency that are sensitive to electronic
      structure changes as a function of d-electron occupancy in the redox orbital. It
      is shown that the large fold angle differences correlate with covalency, and the
      fold angle distortion is due to a pseudo-Jahn-Teller (PJT) effect. The PJT effect
      in these and related transition metal dithiolene systems arises from the small
      energy differences between metal and sulfur valence molecular orbitals, which
      uniquely poise these systems for dramatic geometric and electronic structure
      changes as the oxidation state changes. Herein, we have used a combination of
      resonance Raman, magnetic circular dichroism, electron paramagnetic resonance,
      and UV photoelectron spectroscopies to explore the electronic states involved in
      the vibronic coupling mechanism. Comparison between the UV photoelectron
      spectroscopy (UPS) of the d2 M = Mo complex and the resonance Raman spectra of
      the d1 M = V complex reveals the power of this combined spectroscopic approach.
      Here, we observe that the UPS spectrum of Cp2Mo(bdt) contains an intriguing
      vibronic progession that is dominated by a "missing-mode" that is composed of PJT
      active distortions. We discuss the relationship of the PJT distortions to facile
      electron transfer in molybdenum enzymes.

PMID- 30208275
TI  - Bacterial Cellulose as a Supersoft Neural Interfacing Substrate.
AB  - Biocompatible neural interfaces hold great promise for treating neurological
      disorders and enhancing the mental and physical ability of human beings. Most of
      the currently available neural interfaces are made from rigid, dense inorganic
      materials that cause tissue damage. We present supersoft multichannel electrodes
      by depositing gold layers on thin bacterial cellulose (BC) (Au-BC electrodes).
      The Young's modulus of BC ( EBC = 120 kPa) is between those of the brain tissue (
      Ebrain = 2.7-3.1 kPa) and the peripheral neural tissues ( Eperipheral nerve = 580
      840 kPa). The bending stiffness of the Au-BC electrodes corresponds to 1/5200 of
      Au-polyimide electrodes with the same layout. Furthermore, the Au-BC electrodes
      are highly durable (conductivity >95% after 100 cycles of 180 degrees  bending).
      In vivo recording of brain electric activity demonstrates the great potential of
      the Au-BC electrodes for neural interfacing applications.

PMID- 30208277
TI  - Synthesis of Diketones, Ketoesters, and Tetraketones by Electrochemical Oxidative
      Decarboxylation of Malonic Acid Derivatives: Application to the Synthesis of cis
      Jasmone.
AB  - Disubstituted malonic acid derivatives are smoothly converted into diketones and
      ketoesters in good to excellent yield (68% to 91%) under electrochemical
      conditions. The scope can be extended to transform trisubstituted bis-malonic
      acids into tetraketones in 77% to 86% yield. The new method was applied to the
      total synthesis of cis-jasmone.

PMID- 30208276
TI  - Highly Sensitive Quantification Method for Amine Submetabolome Based on AQC
      Labeled-LC-Tandem-MS and Multiple Statistical Data Mining: A Potential Cancer
      Screening Approach.
AB  - The relationship between amine submetabolome and cancer has been increasingly
      investigated. However, no study was performed to evaluate the current methods of
      amine submetabolomics comprehensively, or to use such quantification results to
      provide an applicable approach for cancer screening. In this study, a highly
      sensitive and practical workflow for quantifying amine submetabolome, which was
      based on 6-aminoquinolyl- N-hydroxysuccinimidyl carbamate (AQC)-labeled-HPLC
      MS/MS analysis combined with multiple statistical data processing approach, was
      established and optimized. Comparison and optimization of two analytical
      approaches, HILIC separation and precolumn derivatization, and three types of
      surrogate matrices of plasma were performed systematically. The detection
      sensitivities of AQC-labeled amines were increased by 50-1000-fold compared with
      the underivatization-HILIC method. Surrogate matrix was also used to verify the
      method after a large dilution factor was employed. In data analysis, the specific
      amino-index for each cancer sample was identified and validated by univariate
      receiver operating characteristic (ROC) curve analysis, partial least-squares
      discrimination analysis (PLS-DA), and multivariate ROC curve analysis. These
      amino indexes were innovatively quantified by multiplying the raised markers and
      dividing the reduced markers. As a result, the numerical intervals of amino
      indexes for healthy volunteers and cancer patients were provided, and their
      clinical value was also improved. Finally, the integrated workflow successfully
      differentiated the value of the amino index for plasma of lung, breast,
      colorectal, and gastric cancer samples from controls and among different types of
      cancer. Furthermore, it was also used to evaluate therapeutic effects. Taken
      together, the developed methodology, which was characterized by high sensitivity,
      high throughput, and high practicality, is suitable for amine submetabolomics in
      studying cancer biomarkers and could also be applied in many other clinical and
      epidemiological research.

PMID- 30208279
TI  - Improving hepatic mitochondrial biogenesis as a postulated mechanism for the
      antidiabetic effect of Spirulina platensis in comparison with metformin.
AB  - Various nutritional and medicinal potencies have been accredited to metabolites
      from the cyanobacteria, Spirulina platensis (Arthrospira platensis) sp. Hence,
      our study was designed to examine whether the Spirulina supplementation would
      possess beneficial effects in type 2 diabetes mellitus (T2DM), in comparison with
      metformin. High fat diet/low dose streptozotocin (HFD/STZ) model was adopted and
      the diabetic rats were orally treated with metformin (200 mg/kg) or Spirulina
      (250 or 500 or 750 mg/kg) for 30 days. Spirulina ameliorated the HFD/STZ-induced
      elevation of fasting blood glucose, insulin and hepatic enzymes. Moreover,
      Spirulina successfully rectified disrupted serum lipid profile and exhibited an
      anti-inflammatory effect via tumor necrosis factor-alpha and adiponectin
      modulation. On the molecular level, Spirulina reduced the expression of hepatic
      sterol regulatory element binding protein-1c (SREBP-1c), confirming its
      lipotropic effect. Furthermore, Spirulina amended compromised hepatic
      mitochondrial biogenesis signaling by significantly increasing peroxisome
      proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha),
      mitochondrial transcription factor A (Tfam) and mitochondrial DNA (mtDNA) copy
      number. On almost all parameters, the highest dose of Spirulina showed the best
      effects; which were comparable to that of metformin. To our knowledge, our study
      is the first to attribute the various aspects of the effect of Spirulina to the
      SREBP-1c and PGC-1alpha/Tfam/mtDNA pathways in liver. The present results clearly
      proved that Spirulina modulated glucose/lipid profile and exhibited prominent
      anti-inflammatory properties through SREBP-1c inhibition and hepatic
      mitochondrial biogenesis enhancement. Thus, Spirulina can be considered as an add
      on to conventional antidiabetic agents and might influence the whole dynamics of
      the therapeutic approaches in T2DM.

PMID- 30208280
TI  - Renal collecting duct physiology and pathophysiology.
AB  - In the kidney, the collecting duct (CD) is composed of at least four cell types:
      principal, type-A intercalated cells (IC), type-B IC, and non-A and non-B IC.
      Although this heterogeneous composition has been recognized since the end of the
      nineteenth century, the physiological role of the various cell types in the CD
      continues to be deciphered as of today. Principal and ICs are essential in ion
      water balance and acid-base homeostasis, respectively. However, recent research
      has revealed a striking interplay and overlap between the specific functions of
      these cell types. This review summarizes the recent findings on CD cells and
      their role in multiple pathophysiologies.

PMID- 30208281
TI  - Nuclear Receptors as Therapeutic Targets for Neurodegenerative Diseases: Lost in
      Translation.
AB  - Neurodegenerative diseases are characterized by a progressive loss of neurons
      that leads to a broad range of disabilities, including severe cognitive decline
      and motor impairment, for which there are no effective therapies. Several lines
      of evidence support a putative therapeutic role of nuclear receptors (NRs) in
      these types of disorders. NRs are ligand-activated transcription factors that
      regulate the expression of a wide range of genes linked to metabolism and
      inflammation. Although the activation of NRs in animal models of
      neurodegenerative disease exhibits promising results, the translation of this
      strategy to clinical practice has been unsuccessful. In this review we discuss
      the role of NRs in neurodegenerative diseases in light of preclinical and
      clinical studies, as well as new findings derived from the analysis of
      transcriptomic databases from humans and animal models. We discuss the failure in
      the translation of NR-based therapeutic approaches and consider alternative and
      novel research avenues in the development of effective therapies for
      neurodegenerative diseases. Expected final online publication date for the Annual
      Review of Pharmacology and Toxicology Volume 59 is January 6, 2019. Please see
      http://www.annualreviews.org/page/journal/pubdates for revised estimates.

PMID- 30208282
TI  - Surviving in the Valley of Death: Opportunities and Challenges in Translating
      Academic Drug Discoveries.
AB  - With pharmaceutical companies shrinking their research departments and exiting
      out of efforts related to unprofitable diseases, society has become increasingly
      dependent on academic institutions to perform drug discovery and early-stage
      translational research. Academic drug discovery and translational research
      programs assist in shepherding promising therapeutic opportunities through the so
      called valley of death in the hope that a successful new drug will result in
      saved lives, improved health, economic growth, and financial return. We have
      interviewed directors of 16 such academic programs in the United States and found
      that these programs and the projects therein face numerous challenges in reaching
      the clinic, including limited funding, lack of know-how, and lack of a regional
      drug development ecosystem. If these issues can be addressed through novel
      industry partnerships, the revision of government policies, and expanded programs
      in translational education, more effective new therapies are more likely to reach
      patients in need. Expected final online publication date for the Annual Review of
      Pharmacology and Toxicology Volume 59 is January 6, 2019. Please see
      http://www.annualreviews.org/page/journal/pubdates for revised estimates.

PMID- 30208284
TI  - Bepotastine besilate for the treatment of perennial allergic rhinitis.
AB  - INTRODUCTION: Bepotastine besilate (BB) is a second-generation H1-antihistamine
      that, as an ophthalmic solution, is approved in the United States by the Food and
      Drug Administration (FDA) for the treatment of allergic conjunctivitis. In other
      countries, the oral presentation of BB is widely used for the improvement of
      symptoms of allergic rhinitis (AR) as well as urticaria and chronic pruritus with
      results similar to those by other drugs of the same class. Areas covered: This
      article was created from a comprehensive literature search with information taken
      from clinical trials. The articles that have been selected evaluate the clinical
      and non-clinical pharmacology of BB as well as its use in AR and its efficiency
      in the improvement of symptoms, its safety, common adverse effects, and overall
      experiences of its use. Expert opinion: BB is effective and well-tolerated in the
      treatment of allergic rhinitis. Side effects are infrequent in patients with AR
      who do not have kidney or liver disease. Clinical trial experience with oral
      bepotastine outside the United States has confirmed its safety. BB can be useful
      as a therapeutic option in patients with AR who would like to explore an
      alternative to the currently available once-daily oral H1-antihistamines.

PMID- 30208283
TI  - BANFF: bending of bilayer membranes by amphiphilic alpha-helices is necessary for
      form and function of organelles.
AB  - By binding to and inserting into the lipid bilayer, amphiphilic alpha-helices of
      proteins are involved in the curvature of biological membranes in all organisms.
      In particular, they are involved in establishing the complex membrane
      architecture of intracellular organelles like the endoplasmatic reticulum, Golgi
      apparatus, mitochondria, and chloroplasts. Thus, amphiphilic alpha-helices are
      essential for maintenance of cellular metabolism and fitness of organisms. Here
      we focus on the structure and function of membrane-intrinsic proteins, which are
      involved in membrane curvature by amphiphilic alpha-helices, in mitochondria and
      chloroplasts of the eukaryotic model organisms yeast and Arabidopsis thaliana.
      Further, we propose a model for transport of fatty acids and lipid compounds
      across the envelope of chloroplasts in which amphiphilic alpha-helices might play
      a role.

PMID- 30208285
TI  - Commentary on Measurement in Lactation and Breastfeeding.

PMID- 30208286
TI  - HISPIDORHYNCHUS STYRACURAE N. SP. (TRYPANORHYNCHA: EUTETRARHYNCHIDAE) FROM THE
      CHUPARE STINGRAY, STYRACURA SCHMARDAE (WERNER), FROM THE CARIBBEAN SEA, INCLUDING
      NEW RECORDS OF ONCOMEGAS WAGENERI (LINTON, 1890).
AB  - Species of the eutetrarhynchid genus Hispidorhynchus Schaeffner and Beveridge,
      2012 possess an uncinate macrohook on the bothrial surface of the basal swelling
      of each tentacle. This unique feature of the oncotaxy is only shared with the
      closely-related genus Oncomegas Dollfus, 1929. A new species of Hispidorhynchus
      is described from specimens infecting Styracura schmardae (Werner, 1904)
      (Potamotrygonidae) from the western Caribbean Sea off the coast of Belize and
      Panama. Hispidorhynchus styracurae n. sp. differs from its 3 congeners in the
      possession of smaller and narrower bulbs, fewer principle hooks in the metabasal
      armature, size of the macrohook and different scolex proportions. Scanning
      electron microscopy reveals new information on the microthrix morphology of the
      genus. A diagnostic key for the differentiation of species of Hispidorhynchus is
      provided. In addition, new host and locality records are reported for Oncomegas
      wageneri (Linton, 1890) Dollfus, 1929 collected from Hypanus guttatus (Bloch and
      Schneider, 1801) (Dasyatidae) off the coast of Maceio, Alagoas (Brazil). This
      considerably expands the geographical distribution of this species in the western
      Atlantic Ocean.

PMID- 30208287
TI  - Phage-Encoded Anti-CRISPR Defenses.
AB  - The battle for survival between bacteria and bacteriophages (phages) is an arms
      race where bacteria develop defenses to protect themselves from phages and phages
      evolve counterstrategies to bypass these defenses. CRISPR-Cas adaptive immune
      systems represent a widespread mechanism by which bacteria protect themselves
      from phage infection. In response to CRISPR-Cas, phages have evolved protein
      inhibitors known as anti-CRISPRs. Here, we describe the discovery and mechanisms
      of action of anti-CRISPR proteins. We discuss the potential impact of anti
      CRISPRs on bacterial evolution, speculate on their evolutionary origins, and
      contemplate the possible next steps in the CRISPR-Cas evolutionary arms race. We
      also touch on the impact of anti-CRISPRs on the development of CRISPR-Cas-based
      biotechnological tools.

PMID- 30208288
TI  - Calcium Channelopathies: Structural Insights into Disorders of the Muscle
      Excitation-Contraction Complex.
AB  - Ion channels are membrane proteins responsible for the passage of ions down their
      electrochemical gradients and across biological membranes. In this, they generate
      and shape action potentials and provide secondary messengers for various
      signaling pathways. They are often part of larger complexes containing auxiliary
      subunits and regulatory proteins. Channelopathies arise from mutations in the
      genes encoding ion channels or their associated proteins. Recent advances in cryo
      electron microscopy have resulted in an explosion of ion channel structures in
      multiple states, generating a wealth of new information on channelopathies.
      Disease-associated mutations fall into different categories, interfering with ion
      permeation, protein folding, voltage sensing, ligand and protein binding, and
      allosteric modulation of channel gating. Prime examples of these are Ca2+
      selective channels expressed in myocytes, for which multiple structures in
      distinct conformational states have recently been uncovered. We discuss the
      latest insights into these calcium channelopathies from a structural viewpoint.

PMID- 30208289
TI  - Unique Archaeal Small RNAs.
AB  - Advances in genome-wide sequence technologies allow for detailed insights into
      the complexity of RNA landscapes of organisms from all three domains of life.
      Recent analyses of archaeal transcriptomes identified interaction and regulation
      networks of noncoding RNAs in this understudied domain. Here, we review current
      knowledge of small, noncoding RNAs with important functions for the archaeal
      lifestyle, which often requires adaptation to extreme environments. One focus is
      RNA metabolism at elevated temperatures in hyperthermophilic archaea, which
      reveals elevated amounts of RNA-guided RNA modification and virus defense
      strategies. Genome rearrangement events result in unique fragmentation patterns
      of noncoding RNA genes that require elaborate maturation pathways to yield
      functional transcripts. RNA-binding proteins, e.g., L7Ae and LSm, are important
      for many posttranscriptional control functions of RNA molecules in archaeal
      cells. We also discuss recent insights into the regulatory potential of their
      noncoding RNA partners.

PMID- 30208290
TI  - Chromosome Dynamics in Response to DNA Damage.
AB  - Recent advances in both the technologies used to measure chromatin movement and
      the biophysical analysis used to model them have yielded a fuller understanding
      of chromatin dynamics and the polymer structure that underlies it. Changes in
      nucleosome packing, checkpoint kinase activation, the cell cycle, chromosomal
      tethers, and external forces acting on nuclei in response to external and
      internal stimuli can alter the basal mobility of DNA in interphase nuclei of
      yeast or mammalian cells. Although chromatin movement is assumed to be necessary
      for many DNA-based processes, including gene activation by distal enhancer
      promoter interaction or sequence-based homology searches during double-strand
      break repair, experimental evidence supporting an essential role in these
      activities is sparse. Nonetheless, high-resolution tracking of chromatin dynamics
      has led to instructive models of the higher-order folding and flexibility of the
      chromatin polymer. Key regulators of chromatin motion in physiological conditions
      or after damage induction are reviewed here.

PMID- 30208292
TI  - Shelterin-Mediated Telomere Protection.
AB  - For more than a decade, it has been known that mammalian cells use shelterin to
      protect chromosome ends. Much progress has been made on the mechanism by which
      shelterin prevents telomeres from inadvertently activating DNA damage signaling
      and double-strand break (DSB) repair pathways. Shelterin averts activation of
      three DNA damage response enzymes [the ataxia-telangiectasia-mutated (ATM) and
      ataxia telangiectasia and Rad3-related (ATR) kinases and poly(ADP-ribose)
      polymerase 1 (PARP1)], blocks three DSB repair pathways [classical nonhomologous
      end joining (c-NHEJ), alternative (alt)-NHEJ, and homology-directed repair
      (HDR)], and prevents hyper-resection at telomeres. For several of these
      functions, mechanistic insights have emerged. In addition, much has been learned
      about how shelterin maintains the telomeric 3' overhang, forms and protects the t
      loop structure, and promotes replication through telomeres. These studies
      revealed that shelterin is compartmentalized, with individual subunits dedicated
      to distinct aspects of the end-protection problem. This review focuses on the
      current knowledge of shelterin-mediated telomere protection, highlights
      differences between human and mouse shelterin, and discusses some of the
      questions that remain.

PMID- 30208291
TI  - Aging in a Dish: iPSC-Derived and Directly Induced Neurons for Studying Brain
      Aging and Age-Related Neurodegenerative Diseases.
AB  - Age-associated neurological diseases represent a profound challenge in biomedical
      research as we are still struggling to understand the interface between the aging
      process and the manifestation of disease. Various pathologies in the elderly do
      not directly result from genetic mutations, toxins, or infectious agents but are
      primarily driven by the many manifestations of biological aging. Therefore, the
      generation of appropriate model systems to study human aging in the nervous
      system demands new concepts that lie beyond transgenic and drug-induced models.
      Although access to viable human brain specimens is limited and induced
      pluripotent stem cell models face limitations due to reprogramming-associated
      cellular rejuvenation, the direct conversion of somatic cells into induced
      neurons allows for the generation of human neurons that capture many aspects of
      aging. Here, we review advances in exploring age-associated neurodegenerative
      diseases using human cell reprogramming models, and we discuss general concepts,
      promises, and limitations of the field.

PMID- 30208293
TI  - Understanding the Genetic Basis of C4 Kranz Anatomy with a View to Engineering C3
      Crops.
AB  - One of the most remarkable examples of convergent evolution is the transition
      from C3 to C4 photosynthesis, an event that occurred on over 60 independent
      occasions. The evolution of C4 is particularly noteworthy because of the
      complexity of the developmental and metabolic changes that took place. In most
      cases, compartmentalized metabolic reactions were facilitated by the development
      of a distinct leaf anatomy known as Kranz. C4 Kranz anatomy differs from
      ancestral C3 anatomy with respect to vein spacing patterns across the leaf, cell
      type specification around veins, and cell-specific organelle function. Here we
      review our current understanding of how Kranz anatomy evolved and how it
      develops, with a focus on studies that are dissecting the underlying genetic
      mechanisms. This research field has gained prominence in recent years because
      understanding the genetic regulation of Kranz may enable the C3-to-C4 transition
      to be engineered, an endeavor that would significantly enhance crop productivity.

PMID- 30208294
TI  - Recent Advances in Behavioral (Epi)Genetics in Eusocial Insects.
AB  - Eusocial insects live in societies in which distinct family members serve
      specific roles in maintaining the colony and advancing the reproductive ability
      of a few select individuals. Given the genetic similarity of all colony members,
      the diversity of morphologies and behaviors is surprising. Social communication
      relies on pheromones and olfaction, as shown by mutants of orco, the universal
      odorant receptor coreceptor, and through electrophysiological analysis of
      neuronal responses to pheromones. Additionally, neurohormonal factors and
      epigenetic regulators play a key role in caste-specific behavior, such as
      foraging and caste switching. These studies start to allow an understanding of
      the molecular mechanisms underlying social behavior and provide a technological
      foundation for future studies of eusocial insects. In this review, we highlight
      recent findings in eusocial insects that advance our understanding of genetic and
      epigenetic regulations of social behavior and provide perspectives on future
      studies using cutting-edge technologies.

PMID- 30208295
TI  - Motor deficits in 16-month-old male and female 3xTg-AD mice.
AB  - Motor deficits are some of the most prevalent non-cognitive symptoms of
      Alzheimer's disease (AD) with patients showing impairments in speech, gait and
      fine motor skills. We investigated motor behaviour in 16-month-old male and
      female 3xTg-AD mice and their B6129SF2 wildtype (WT) controls. The 3xTg-AD mice
      develop extracellular Abeta plaques and tau tangles in the hippocampus and motor
      cortex between 6 and 9 months of age. Previously we showed that at 6 months of
      age, 3xTg-AD mice performed better on tests of motor coordination and motor
      learning than WT mice. The aim of our experiment was to use a battery of motor
      behaviour tests to determine if this superior motor performance was present in
      older mice. On the Rotarod, the aged 3xTg-AD mice showed better motor
      coordination and learning than WT mice. Although females performed better than
      males, this sex difference was confounded by body weight as females weighed less
      than males. There were no significant genotype or sex differences on the wire
      hang or grid suspension tasks, nor in stride length or stride width, but 3xTg-AD
      mice performed worse than WT mice on the balance beam. In comparison to the 6
      month-old mice, an age-related decline in most aspects of motor behaviour was
      apparent. These results indicate that different sub-domains of motor function are
      affected differently in the 3xTg-AD mice and that aging does not have the same
      effect on all motor behaviours.

PMID- 30208296
TI  - A ReliefF-SVM-based method for marking dopamine-based disease characteristics: A
      study on SWEDD and Parkinson's disease.
AB  - Parkinson's disease (PD) and scans without evidence of dopaminergic deficit
      (SWEDD) are two distinct neurological disorders that require different
      therapeutic approaches; therefore it's critical to classify the two disorders.
      The neuroimaging technology based on dMRI provided connectivity information and
      voxel features that can make it possible for researchers to analyze SWEDD and PD
      differences. In this work, a novel method of ReliefF-SVM-based dMRI analysis was
      presented to study the potential relations between PD and SWEDD. Some
      sensorimotor connections were found group-wise differences, and SVM was suggested
      to successfully classify PD and SWEDD. These results indicate that our method
      using connectivity information and voxel features may provide a new strategy for
      disease analysis with small sample data.

PMID- 30208297
TI  - A review of infrared thermography as applied to human sexual psychophysiology.
AB  - Infrared thermography (IRT) is a non-contact technique that permits mapping and
      analysis of the temperature of the body's skin surface. This method has been
      applied to sexual psychophysiology since the 1980s and its use has been expanding
      ever since, mainly because it provides several advantages over existing genital
      response measures. This article presents a review of experimental studies
      employing IRT to investigate human sexual arousal, with the aim of summarizing
      the available procedures and evidence so far and to identify important caveats in
      the literature. The studies reviewed support the feasibility and validity of IRT
      as a real-time physiological measure of sexual arousal but varied substantially
      regarding methodology and procedures. The results of this review underscore the
      value and validity of IRT in sexual psychophysiology and point at the critical
      need for the standardization of IRT protocols to accommodate the specific needs
      of applying this methodology to sexual physiology.

PMID- 30208298
TI  - Haploids, polymorphisms and fluctuating selection.
AB  - I analyze the joint impact of directional and fluctuating selection with
      reversible mutation in finite bi-allelic haploid populations using diffusion
      approximations of the Moran and chemostat models. Results differ dramatically
      from those of the classic Wright-Fisher diffusion. There, a strong dispersive
      effect attributable to fluctuating selection dissipates nascent polymorphisms
      promoted by a relatively weak emergent frequency dependent selective effect. The
      dispersive effect in the Moran diffusion with fluctuations every birth-death
      event is trivial. The same frequency dependent selective effect now dominates and
      polymorphism is promoted. The dispersive effect in the chemostat diffusion with
      fluctuations every generation is identical to that in the Wright-Fisher
      diffusion. Nevertheless, polymorphism is again promoted because the emergent
      frequency dependent effect is doubled, an effect attributable to geometric
      reproduction within generations. Fluctuating selection in the Moran and chemostat
      diffusions can also promote bi-allelic polymorphisms when one allele confers a
      net benefit. Rapid fluctuations within generations are highly effective at
      promoting polymorphism in large populations. The bi-allelic distribution is
      approximately Gaussian but becomes uniform and then U-shaped as the frequency of
      environmental fluctuations decreases to once a generation and then once every
      multiple generations. Trade-offs (negative correlations in fitness) help promote
      polymorphisms but are not essential. In all three models the frequency dependent
      effect raises the probability of ultimate fixation of new alleles, but less
      effectively in the Wright-Fisher diffusion. Individual-based forward simulations
      confirm the calculations.

PMID- 30208299
TI  - Insulin-loaded hydroxypropyl methyl cellulose-co-polyacrylamide-co-methacrylic
      acid hydrogels used as rectal suppositories to regulate the blood glucose of
      diabetic rats.
AB  - The purpose of this study was developing a novel hydroxypropyl methyl cellulose
      co-polyacrylamide-co-methacrylic acid (HPMC-co-PAM-co-PMAA) hydrogel, which was
      used as rectal suppository to regulate the blood glucose of diabetes. HPMC-co-PAM
      co-PMAA hydrogel was fabricated via free-radical polymerization. Fourier
      transform infrared spectroscopy (FTIR) and Raman spectra were used to confirm the
      fabrication of HPMC-co-PAM-co-PMAA hydrogel. Their inner morphology was observed
      with scanning electron microscope (SEM). The extracts of hydrogel were applied to
      study their cell viability. The hypoglycemic effects of insulin (INS)-loaded HPMC
      co-PAM-co-PMAA hydrogels were investigated by rectal administration. FTIR and
      Raman spectra confirmed the obtaining of HPMC-co-PAM-co-PMAA hydrogels. Many
      micro-pores were found in the SEM photograph of HPMC-co-PAM-co-PMAA hydrogels.
      Cell experiments indicated that HPMC-co-PAM-co-PMAA hydrogel was out of
      cytotoxicity. In vitro release profiles showed that INS-loaded hydrogel could
      release INS at a continuous manner in pH 7.4 buffer (rectal conditions). Animal
      experiments suggested that INS-loaded hydrogel had an obvious hypoglycemic
      effect. Therefore, as a convenient and economic method of administration, INS
      loaded HPMC-co-PAM-co-PMAA hydrogels could be used as rectal suppositories to
      regulate blood glucose.

PMID- 30208300
TI  - A review on processing techniques of bast fibers nanocellulose and its polylactic
      acid (PLA) nanocomposites.
AB  - The utilization of nanocellulose has increasingly gained attentions from various
      research fields, especially the field of polymer nanocomposites owing to the
      growing environmental hazardous of petroleum based fiber products. Meanwhile, the
      searching of alternative cellulose sources from different plants has become the
      interests for producing nanocellulose with varying characterizations that
      expectedly suit in specific field of applications. In this content the long and
      strong bast fibers from plant species was gradually getting its remarkable
      position in the field of nanocellulose extraction and nanocomposites
      fabrications. This review article intended to present an overview of the chemical
      structure of cellulose, different types of nanocellulose, bast fibers
      compositions, structure, polylactic acid (PLA) and the most probable processing
      techniques on the developments of nanocellulose from different bast fibers
      especially jute, kenaf, hemp, flax, ramie and roselle and its nanocomposites.
      This article however more focused on the fabrication of PLA based nanocomposites
      due to its high firmness, biodegradability and sustainability properties in
      developed products towards the environment. Along with this it also explored a
      couple of issues to improve the processing techniques of bast fibers
      nanocellulose and its reinforcement in the PLA biopolymer as final products.

PMID- 30208301
TI  - Trigonelline prevents high cholesterol and high fat diet induced hepatic lipid
      accumulation and lipo-toxicity in C57BL/6J mice, via restoration of hepatic
      autophagy.
AB  - Non-alcoholic fatty liver disease (NAFLD) is often linked with impaired hepatic
      autophagy. Here, we studied the alterations in hepatocellular autophagy by high
      cholesterol and high-fat diet (HC-HF) diet in C57BL/6J mice, and by palmitic acid
      (PA), in AML-12 and HepG2 cells. Further, we analysed role of Trigonelline (TG),
      a plant alkaloid, in preventing NAFLD, by modulating autophagy. For this,
      C57BL/6J mice were fed with Standard Chow (SC) or HC-HF diet, with and without TG
      for 16 weeks. In-vitro; AML-12 cells and HepG2 cells, were exposed to PA with and
      without TG, for 24 h. Cellular events related to autophagy, lipogenesis, and lipo
      toxicity were studied. The HC-HF diet fed mice showed hepatic autophagy blockade,
      increased triglycerides and steatosis. PA exposure to AML-12 cells and HepG2
      cells induced impaired autophagy, ER stress, resulting in lipotoxicity. TG
      treatment in HC-HF fed mice, restored hepatic autophagy, and prevented steatosis.
      TG treated AML-12, and HepG2 cells exposed to PA showed autophagy restoration,
      and reduced lipotoxicity, however, these effects were diminished in Atg7-/- HepG2
      cells, and in the presence of chloroquine. This study shows that HC-HF diet
      induced impaired autophagy, and steatosis is prevented by TG, which attributes to
      its novel mechanism in treating NAFLD.

PMID- 30208302
TI  - Biomarker correlates of psychotherapy outcomes in borderline personality
      disorder: A systematic review.
AB  - Studies of neurobiological mechanisms in borderline personality disorder (BPD)
      have increased our understanding of the pathophysiology of its development and
      course. Less is known about how psychotherapy may influence these neurobiological
      factors, and also whether biomarkers may predict psychotherapy outcomes. We
      conducted a systematic review using PRISMA guidelines. Fourteen studies providing
      data from 467 participants diagnosed with BPD met inclusion criteria to: (a)
      investigate biomarkers predicting response to psychotherapy for BPD; or (b)
      examine neurobiological factors altered by psychotherapy. Neuroimaging studies (n
      = 11) used mostly functional magnetic resonance imaging methods to scope brain
      regions related to emotion regulation and cognitive control. Three studies
      examined genetic or neuroendocrine markers. The evidence suggests that
      psychotherapy alters neural activation and connectivity of regions subserving
      executive control and emotion regulation. Additionally, hypoactivation in
      prefrontal and cingulate regions predicted treatment response. Further work in
      this area may inform personalised treatment approaches in clinical practice for
      BPD through elucidating neural mechanisms of evidence-based psychotherapy.

PMID- 30208303
TI  - Women in Stem Cell Science: Part I.
AB  - Female scientists play important leadership roles in the field and with the
      International Society for Stem Cell Research. We asked a number of these top
      researchers to share their personal stories and reflect on their career paths.
      Part II of this series will run in the October 2018 issue of Stem Cell Reports.

PMID- 30208305
TI  - Respect and admiration differentially activate the anterior temporal lobe.
AB  - Admiration and respect are positive social emotions often experienced when
      recognizing excellent behavior in another person. Although both strongly rely on
      appraisal of behavior, admiration focuses on the admirable behavior of a person,
      while respect focuses on the person as a whole. The evaluation and interpretation
      of the social behavior of another person are dependent on semantic memory. Social
      semantic knowledge is represented in the anterior temporal lobe (ATL), and ATL
      activity is modulated by conceptual details of semantic knowledge. As respect
      requires evaluation of not only excellent behavior but also of the person as a
      whole, we hypothesized that the ATL is differentially activated by admiration and
      respect. To test our hypothesis, we conducted functional magnetic resonance
      imaging experiments. We presented participants with vignettes describing
      admirable behavior of fictitious characters and asked them to imagine and report
      how they would normally feel when encountering the situation described in the
      vignettes, i.e., admiration or respect and its intensity. A part of the left ATL
      was more strongly modulated by the intensity of respect than of admiration.
      Although admiration and respect are often considered to be closely related, our
      results indicate that the neural substrates underlying these emotions are
      different.

PMID- 30208304
TI  - Analysis of Runx1 Using Induced Gene Ablation Reveals Its Essential Role in Pre
      liver HSC Development and Limitations of an In Vivo Approach.
AB  - Hematopoietic stem cells (HSCs) develop in the embryonic aorta-gonad-mesonephros
      (AGM) region and subsequently relocate to fetal liver. Runx1 transcription factor
      is essential for HSC development, but is largely dispensable for adult HSCs.
      Here, we studied tamoxifen-inducible Runx1 inactivation in vivo. Induction at pre
      liver stages (up to embryonic day 10.5) reduced erythromyeloid progenitor
      numbers, but surprisingly did not block the appearance of Runx1-null HSCs in
      liver. By contrast, ex vivo analysis showed an absolute Runx1 dependency of HSC
      development in the AGM region. We found that, contrary to current beliefs,
      significant Cre-inducing tamoxifen activity persists in mouse blood for at least
      72 hr after injection. This deferred recombination can hit healthy HSCs, which
      escaped early Runx1 ablation and result in appearance of Runx1-null HSCs in
      liver. Such extended recombination activity in vivo is a potential source of
      misinterpretation, particularly in analysis of dynamic developmental processes
      during embryogenesis.

PMID- 30208306
TI  - Peeking into the sleeping brain: Using in vivo imaging in rodents to understand
      the relationship between sleep and cognition.
AB  - Sleep is well known to benefit cognitive function. In particular, sleep has been
      shown to enhance learning and memory in both humans and animals. While the
      underlying mechanisms are not fully understood, it has been suggested that brain
      activity during sleep modulates neuronal communication through synaptic
      plasticity. These insights were mostly gained using electrophysiology to monitor
      ongoing large scale and single cell activity. While these efforts were
      instrumental in the characterisation of important network and cellular activity
      during sleep, several aspects underlying cognition are beyond the reach of this
      technology. Neuronal circuit activity is dynamically regulated via the precise
      interaction of different neuronal and non-neuronal cell types and relies on
      subtle modifications of individual synapses. In contrast to established
      electrophysiological approaches, recent advances in imaging techniques, mainly
      applied in rodents, provide unprecedented access to these aspects of neuronal
      function in vivo. In this review, we describe various techniques currently
      available for in vivo brain imaging, from single synapse to large scale network
      activity. We discuss the advantages and limitations of these approaches in the
      context of sleep research and describe which particular aspects related to
      cognition lend themselves to this kind of investigation. Finally, we review the
      few studies that used in vivo imaging in rodents to investigate the sleeping
      brain and discuss how the results have already significantly contributed to a
      better understanding on the complex relation between sleep and plasticity across
      development and adulthood.

PMID- 30208307
TI  - Layer 2/3 Pyramidal Neurons Control the Gain of Cortical Output.
AB  - Initial anatomical and physiological studies suggested that sensory information
      relayed from the periphery by the thalamus is serially processed in primary
      sensory cortical areas. It is thought to propagate from layer 4 (L4) up to L2/3
      and down to L5, which constitutes the main output of the cortex. However, more
      recent experiments point toward the existence of a direct processing of thalamic
      input by L5 neurons. Therefore, the role of L2/3 neurons in the sensory
      processing operated by L5 neurons is now highly debated. Using cell type-specific
      and reversible optogenetic manipulations in the somatosensory cortex of both
      anesthetized and awake mice, we demonstrate that L2/3 pyramidal neurons play a
      major role in amplifying sensory-evoked responses in L5 neurons. The
      amplification effect scales with the velocity of the sensory stimulus, indicating
      that L2/3 pyramidal neurons implement gain control in deep-layer neurons.

PMID- 30208308
TI  - The LKB1-SIK Pathway Controls Dendrite Self-Avoidance in Purkinje Cells.
AB  - Strictly controlled dendrite patterning underlies precise neural connection.
      Dendrite self-avoidance is a crucial system preventing self-crossing and clumping
      of dendrites. Although many cell-surface molecules that regulate self-avoidance
      have been identified, the signaling pathway that orchestrates it remains poorly
      understood, particularly in mammals. Here, we demonstrate that the LKB1-SIK
      kinase pathway plays a pivotal role in the self-avoidance of Purkinje cell (PC)
      dendrites by ensuring dendritic localization of Robo2, a regulator of self
      avoidance. LKB1 is activated in developing PCs, and PC-specific deletion of LKB1
      severely disrupts the self-avoidance of PC dendrites without affecting gross
      morphology. SIK1 and SIK2, downstream kinases of LKB1, mediate LKB1-dependent
      dendrite self-avoidance. Furthermore, loss of LKB1 leads to significantly
      decreased Robo2 levels in the dendrite but not in the cell body. Finally,
      restoration of dendritic Robo2 level via overexpression largely rescues the self
      avoidance defect in LKB1-deficient PCs. These findings reveal an LKB1-pathway
      mediated developmental program that establishes dendrite self-avoidance.

PMID- 30208309
TI  - Local Integrin Activation in Pancreatic beta Cells Targets Insulin Secretion to
      the Vasculature.
AB  - The extracellular matrix (ECM) critically affects beta cell functions via
      integrin activation. But whether these ECM actions drive the spatial organization
      of beta cells, as they do in epithelial cells, is unknown. Here, we show that
      within islets of Langerhans, focal adhesion activation in beta cells occurs
      exclusively where they contact the capillary ECM (vascular face). In cultured
      beta cells, 3D mapping shows enriched insulin granule fusion where the cells
      contact ECM-coated coverslips, which depends on beta1 integrin receptor
      activation. Culture on micro-contact printed stripes of E-cadherin and
      fibronectin shows that beta cell contact at the fibronectin stripe selectively
      activates focal adhesions and enriches exocytic machinery and insulin granule
      fusion. Culture of cells in high glucose, as a model of glucotoxicity, abolishes
      granule targeting. We conclude that local integrin activation targets insulin
      secretion to the islet capillaries. This mechanism might be important for islet
      function and may change in disease.

PMID- 30208310
TI  - Gamma-Aminobutyric Acid Signaling in Brown Adipose Tissue Promotes Systemic
      Metabolic Derangement in Obesity.
AB  - Brown adipose tissue (BAT) is a metabolically active organ that contributes to
      the maintenance of systemic metabolism. The sympathetic nervous system plays
      important roles in the homeostasis of BAT and promotes its browning and
      activation. However, the role of other neurotransmitters in BAT homeostasis
      remains largely unknown. Our metabolomic analyses reveal that gamma-aminobutyric
      acid (GABA) levels are increased in the interscapular BAT of mice with dietary
      obesity. We also found a significant increase in GABA-type B receptor subunit 1
      (GABA-BR1) in the cell membranes of brown adipocytes of dietary obese mice. When
      administered to obese mice, GABA induces BAT dysfunction together with systemic
      metabolic disorder. Conversely, the genetic inactivation or inhibition of GABA
      BR1 leads to the re-browning of BAT under conditions of metabolic stress and
      ameliorated systemic glucose intolerance. These results indicate that the
      constitutive activation of GABA/GABA-BR1 signaling in obesity promotes BAT
      dysfunction and systemic metabolic derangement.

PMID- 30208312
TI  - Interrogating the ccm-3 Gene Network.
AB  - Cerebral cavernous malformations (CCMs) are neurovascular lesions caused by
      mutations in one of three genes (CCM1-3). Loss of CCM3 causes the poorest
      prognosis, and little is known about how it regulates vascular integrity. The C.
      elegans ccm-3 gene regulates the development of biological tubes that resemble
      mammalian vasculature, and in a genome-wide reverse genetic screen, we identified
      more than 500 possible CCM-3 pathway genes. With a phenolog-like approach, we
      generated a human CCM signaling network and identified 29 genes in common, of
      which 14 are required for excretory canal extension and membrane integrity,
      similar to ccm-3. Notably, depletion of the MO25 ortholog mop-25.2 causes severe
      defects in tube integrity by preventing CCM-3 localization to apical membranes.
      Furthermore, loss of MO25 phenocopies CCM3 ablation by causing stress fiber
      formation in endothelial cells. This work deepens our understanding of how CCM3
      regulates vascular integrity and may help identify therapeutic targets for
      treating CCM3 patients.

PMID- 30208313
TI  - Activation of Ras in the Vascular Endothelium Induces Brain Vascular
      Malformations and Hemorrhagic Stroke.
AB  - Cerebrovascular malformations (CVMs) affect approximately 3% of the population,
      risking hemorrhagic stroke, seizures, and neurological deficits. Recently Ras
      mutations have been identified in a majority of brain arterio-venous
      malformations. We generated an endothelial-specific, inducible HRASV12 mouse
      model, which results in dilated, proliferative blood vessels in the brain, blood
      brain barrier breakdown, intracerebral hemorrhage, and rapid lethality. Organoid
      morphogenesis models revealed abnormal cessation of proliferation, abnormalities
      in expression of tip and stalk genes, and a failure to properly form elongating
      tubes. These defects were influenced by both hyperactive PI-3' kinase signaling
      and altered TGF-beta signaling. Several phenotypic changes predicted by the in
      vitro morphogenesis analysis were validated in the mouse model. These data
      provide a model of brain vascular malformations induced by mutant Ras and reveal
      insights into intersecting molecular mechanisms in the pathogenesis of brain
      vascular malformations.

PMID- 30208315
TI  - The Atypical Kinesin KIF26A Facilitates Termination of Nociceptive Responses by
      Sequestering Focal Adhesion Kinase.
AB  - Kinesin superfamily proteins (KIFs) are molecular motors that typically alter the
      subcellular localization of their cargos. However, the atypical kinesin KIF26A
      does not serve as a motor but can bind microtubules and affect cellular signaling
      cascades. Here, we show that KIF26A maintains intracellular calcium homeostasis
      and negatively regulates nociceptive sensation. Kif26a-/- mice exhibit intense
      and prolonged nociceptive responses. In their primary sensory neurons, excessive
      inhibitory phosphorylation of plasma membrane Ca2+ ATPase (PMCA) mediated by
      focal adhesion kinase (FAK) rendered the Ca transients resistant to termination,
      and the peripheral axonal outgrowth was significantly enhanced. Upstream, KIF26A
      is directly associated with a FERM domain of FAK and antagonizes FAK function in
      integrin-Src family kinase (SFK)-FAK signaling, possibly through steric hindrance
      and localization to cytoplasmic microtubules.

PMID- 30208314
TI  - Dual Dopaminergic Regulation of Corticostriatal Plasticity by Cholinergic
      Interneurons and Indirect Pathway Medium Spiny Neurons.
AB  - Endocannabinoid (eCB)-mediated long-term depression (LTD) requires dopamine (DA)
      D2 receptors (D2Rs) for eCB mobilization. The cellular locus of the D2Rs involved
      in LTD induction remains highly debated. We directly examined the role in LTD
      induction of D2Rs expressed by striatal cholinergic interneurons (Chls) and
      indirect pathway medium spiny neurons (iMSNs) using neuron-specific targeted
      deletion of D2Rs. Deletion of Chl-D2Rs (Chl-Drd2KO) impaired LTD induction in
      both subtypes of MSNs. LTD induction was restored in the Chl-Drd2KO mice by an M1
      selective muscarinic acetylcholine receptor antagonist. In contrast, after the
      deletion of iMSN-D2Rs (iMSN-Drd2KO), LTD induction was intact in MSNs. Separate
      interrogation of direct pathway and iMSNs revealed a deficit in LTD induction
      only at synapses onto iMSNs that lack D2Rs. LTD induction in iMSNs was restored
      by D2R agonist application. Our findings suggest that Chl D2Rs strongly modulate
      LTD induction in MSNs, with iMSN-D2Rs having a weaker, iMSN-specific, modulatory
      effect.

PMID- 30208317
TI  - Sarcolipin Signaling Promotes Mitochondrial Biogenesis and Oxidative Metabolism
      in Skeletal Muscle.
AB  - The major objective of this study was to understand the molecular basis of how
      sarcolipin uncoupling of SERCA regulates muscle oxidative metabolism. Using
      genetically engineered sarcolipin (SLN) mouse models and primary muscle cells, we
      demonstrate that SLN plays a crucial role in mitochondrial biogenesis and
      oxidative metabolism in muscle. Loss of SLN severely compromised muscle oxidative
      capacity without affecting fiber-type composition. Mice overexpressing SLN in
      fast-twitch glycolytic muscle reprogrammed mitochondrial phenotype, increasing
      fat utilization and protecting against high-fat diet-induced lipotoxicity. We
      show that SLN affects cytosolic Ca2+ transients and activates the Ca2+/calmodulin
      dependent protein kinase II (CamKII) and PGC1alpha axis to increase mitochondrial
      biogenesis and oxidative metabolism. These studies provide a fundamental
      framework for understanding the role of sarcoplasmic reticulum (SR)-Ca2+ cycling
      as an important factor in mitochondrial health and muscle metabolism. We propose
      that SLN can be targeted to enhance energy expenditure in muscle and prevent
      metabolic disease.

PMID- 30208311
TI  - Comparative Analyses of Copy-Number Variation in Autism Spectrum Disorder and
      Schizophrenia Reveal Etiological Overlap and Biological Insights.
AB  - Compelling evidence in Caucasian populations suggests a role for copy-number
      variations (CNVs) in autism spectrum disorder (ASD) and schizophrenia (SCZ). We
      analyzed 1,108 ASD cases, 2,458 SCZ cases, and 2,095 controls in a Japanese
      population and confirmed an increased burden of rare exonic CNVs in both
      disorders. Clinically significant (or pathogenic) CNVs, including those at 29
      loci common to both disorders, were found in about 8% of ASD and SCZ cases, which
      was significantly higher than in controls. Phenotypic analysis revealed an
      association between clinically significant CNVs and intellectual disability. Gene
      set analysis showed significant overlap of biological pathways in both disorders
      including oxidative stress response, lipid metabolism/modification, and genomic
      integrity. Finally, based on bioinformatics analysis, we identified multiple
      disease-relevant genes in eight well-known ASD/SCZ-associated CNV loci (e.g.,
      22q11.2, 3q29). Our findings suggest an etiological overlap of ASD and SCZ and
      provide biological insights into these disorders.

PMID- 30208316
TI  - Mechanisms Underlying the Dual Effect of Polyunsaturated Fatty Acid Analogs on
      Kv7.1.
AB  - Polyunsaturated fatty acid (PUFA) analogs represent a new class of potential anti
      arrhythmic KV7.1 and KV7.1+KCNE1 channel activators. In this study, we describe
      dual independent activating effects of negatively charged PUFA analogs on KV7.1
      and KV7.1+KCNE1 that are dependent on discrete channel motifs. PUFA analogs are
      critically dependent on K326 in S6 of KV7.1 to increase the maximum conductance
      and critically dependent on specific S4 arginines in KV7.1 to shift the voltage
      dependence of channel opening toward negative voltages. Our findings provide
      insights into how KV7.1+KCNE1 activators may interact electrostatically both with
      the pore domain and the voltage-sensing domain to augment channel activity. We
      believe that the molecular understanding of how PUFA analogs induce dual
      independent activating effects is an important step toward the development of
      effective anti-arrhythmic drugs that target KV7.1 channels.

PMID- 30208319
TI  - Disease-Linked Glutarylation Impairs Function and Interactions of Mitochondrial
      Proteins and Contributes to Mitochondrial Heterogeneity.
AB  - Lysine glutarylation (Kglu) of mitochondrial proteins is associated with glutaryl
      CoA dehydrogenase (GCDH) deficiency, which impairs lysine/tryptophan degradation
      and causes destruction of striatal neurons during catabolic crisis with
      subsequent movement disability. By investigating the role of Kglu modifications
      in this disease, we compared the brain and liver glutarylomes of Gcdh-deficient
      mice. In the brain, we identified 73 Kglu sites on 37 mitochondrial proteins
      involved in various metabolic degradation pathways. Ultrastructural immunogold
      studies indicated that glutarylated proteins are heterogeneously distributed in
      mitochondria, which are exclusively localized in glial cells. In liver cells, all
      mitochondria contain Kglu-modified proteins. Glutarylation reduces the catalytic
      activities of the most abundant glutamate dehydrogenase (GDH) and the brain
      specific carbonic anhydrase 5b and interferes with GDH-protein interactions. We
      propose that Kglu contributes to the functional heterogeneity of mitochondria and
      may metabolically adapt glial cells to the activity and metabolic demands of
      neighboring GCDH-deficient neurons.

PMID- 30208318
TI  - Sphingosine Kinase Activates the Mitochondrial Unfolded Protein Response and Is
      Targeted to Mitochondria by Stress.
AB  - The mitochondrial unfolded protein response (UPRmt) is critical for maintaining
      mitochondrial protein homeostasis in response to mitochondrial stress, but early
      steps in UPRmt activation are not well understood. Here, we report a function for
      SPHK-1 sphingosine kinase in activating the UPRmt in C. elegans. Genetic
      deficiency of sphk-1 in the intestine inhibits UPRmt activation, whereas
      selective SPHK-1 intestinal overexpression is sufficient to activate the UPRmt.
      Acute mitochondrial stress leads to rapid, reversible localization of SPHK-1::GFP
      fusion proteins with mitochondrial membranes before UPRmt activation. SPHK-1
      variants lacking kinase activity or mitochondrial targeting fail to rescue the
      stress-induced UPRmt activation defects of sphk-1 mutants. Activation of the
      UPRmt by the nervous system requires sphk-1 and elicits SPHK-1 mitochondrial
      association in the intestine. We propose that stress-regulated mitochondrial
      recruitment of SPHK-1 and subsequent S1P production are critical early events for
      both cell autonomous and cell non-autonomous UPRmt activation.

PMID- 30208321
TI  - MRT, Functioning with NURF Complex, Regulates Lipid Droplet Size.
AB  - Lipid droplets (LDs) are highly dynamic organelles that store neutral lipids.
      Through a gene overexpression screen in the Drosophila larval fat body, we have
      identified that MRT, an Myb/switching-defective protein 3 (Swi3), Adaptor 2
      (Ada2), Nuclear receptor co-repressor (N-CoR), Transcription factor (TF)IIIB
      (SANT)-like DNA-binding domain-containing protein, regulates LD size and lipid
      storage. MRT directly interacts with, and is functionally dependent on, the PZG
      and NURF chromatin-remodeling complex components. MRT binds to the promoter of
      plin1, the gene encoding the LD-resident protein perilipin, and inhibits the
      transcription of plin1. In vitro LD coalescence assays suggest that mrt
      overexpression or loss of plin1 function facilitates LD coalescence. Our findings
      suggest that MRT functions together with chromatin-remodeling factors to regulate
      LD size, likely through the transcriptional repression of plin1.

PMID- 30208322
TI  - FXR Inhibits Endoplasmic Reticulum Stress-Induced NLRP3 Inflammasome in
      Hepatocytes and Ameliorates Liver Injury.
AB  - Endoplasmic reticulum (ER) stress is associated with liver injury and fibrosis,
      and yet the hepatic factors that regulate ER stress-mediated inflammasome
      activation remain unknown. Here, we report that farnesoid X receptor (FXR)
      activation inhibits ER stress-induced NACHT, LRR, and PYD domains-containing
      protein 3 (NLRP3) inflammasome in hepatocytes. In patients with hepatitis B virus
      (HBV)-associated hepatic failure or non-alcoholic fatty liver disease, and in
      mice with liver injury, FXR levels in the liver inversely correlated with the
      extent of NLRP3 inflammasome activation. Fxr deficiency in mice augmented the
      ability of ER stress to induce NLRP3 and thioredoxin-interacting protein (TXNIP),
      whereas FXR ligand activation prevented it, ameliorating liver injury. FXR
      attenuates CCAAT-enhancer-binding protein homologous protein (CHOP)-dependent
      NLRP3 overexpression by inhibiting ER stress-mediated protein kinase RNA-like
      endoplasmic reticulum kinase (PERK) activation. Our findings implicate miR-186
      and its target, non-catalytic region of tyrosine kinase adaptor protein 1 (NCK1),
      in mediating the inhibition of ER stress by FXR. This study provides the insights
      on how FXR regulation of ER stress ameliorates hepatocyte death and liver injury
      and on the molecular basis of NLRP3 inflammasome activation.

PMID- 30208320
TI  - GPS2 Deficiency Triggers Maladaptive White Adipose Tissue Expansion in Obesity
      via HIF1A Activation.
AB  - Hypertrophic white adipose tissue (WAT) represents a maladaptive mechanism linked
      to the risk for developing type 2 diabetes in humans. However, the molecular
      events that predispose WAT to hypertrophy are poorly defined. Here, we
      demonstrate that adipocyte hypertrophy is triggered by loss of the corepressor
      GPS2 during obesity. Adipocyte-specific GPS2 deficiency in mice (GPS2 AKO) causes
      adipocyte hypertrophy, inflammation, and mitochondrial dysfunction during surplus
      energy. This phenotype is driven by HIF1A activation that orchestrates inadequate
      WAT remodeling and disrupts mitochondrial activity, which can be reversed by
      pharmacological or genetic HIF1A inhibition. Correlation analysis of gene
      expression in human adipose tissue reveals a negative relationship between GPS2
      and HIF1A, adipocyte hypertrophy, and insulin resistance. We propose therefore
      that the obesity-associated loss of GPS2 in adipocytes predisposes for a
      maladaptive WAT expansion and a pro-diabetic status in mice and humans.

PMID- 30208323
TI  - Regional Differences in Airway Epithelial Cells Reveal Tradeoff between Defense
      against Oxidative Stress and Defense against Rhinovirus.
AB  - Rhinovirus is a leading cause of acute respiratory infections and asthma attacks,
      but infections are also frequently cleared from the nasal mucosa without causing
      symptoms. We sought to better understand host defense against rhinovirus by
      investigating antiviral defense in primary human nasal and bronchial airway
      epithelial cells cultured ex vivo. Surprisingly, upon rhinovirus infection or RIG
      I stimulation, nasal-derived epithelial cells exhibited much more robust
      antiviral responses than bronchial-derived cells. Conversely, RIG-I stimulation
      triggered more robust activation of the NRF2-dependent oxidative stress response
      in bronchial cells compared to nasal cells. NRF2 activation dampened epithelial
      antiviral responses, whereas NRF2 knockdown enhanced antiviral responses and was
      protective during rhinovirus infection. These findings demonstrate a tradeoff in
      epithelial defense against distinct types of airway damage, namely, viral versus
      oxidative, and reveal differential calibration of defense responses in cells
      derived from different airway microenvironments.

PMID- 30208324
TI  - Single-Cell Acoustic Force Spectroscopy: Resolving Kinetics and Strength of T
      Cell Adhesion to Fibronectin.
AB  - Assessing the strength and kinetics of molecular interactions of cells with the
      extracellular matrix is fundamental to understand cell adhesion processes. Given
      the relevance of these processes, there is a strong need for physical methods to
      quantitatively assess the mechanism of cell adhesion at the single-cell level,
      allowing discrimination of cells with different behaviors. Here we introduce
      single-cell acoustic force spectroscopy (scAFS), an approach that makes use of
      acoustic waves to exert controlled forces, up to 1 nN, to hundreds of individual
      cells in parallel. We demonstrate the potential of scAFS by measuring adhesion
      forces and kinetics of CD4+ T lymphocytes (CD4) to fibronectin. We determined
      that CD4 adhesion is accelerated by interleukin-7, their main regulatory
      cytokine, whereas CD4 binding strength remains the same. Activation of these
      cells likely increases their chance to bind to the vessel wall in the blood flow
      to infiltrate inflamed tissues and locally coordinate the immune response.

PMID- 30208325
TI  - Granule-Dependent NK Cell Killing of Cryptococcus Requires Kinesin to Reposition
      the Cytolytic Machinery for Directed Cytotoxicity.
AB  - Cryptococcus is the most important cause of fungal meningitis in
      immunocompromised individuals. Host defense against Cryptococcus involves direct
      killing by NK cells. That NK cells from HIV-infected patients fail to polarize
      perforin to the microbial synapse and kill C. neoformans led us to explore the
      mechanisms used to reposition and polarize the cytolytic granules to the synapse.
      Using live-cell imaging, we observed microtubule and granule movements in
      response to Cryptococcus that revealed a kinesin-dependent event. Eg5-kinesin
      bound to perforin-containing granules and was required for association with the
      microtubules. Inhibition of Eg5-kinesin abrogated dynein-dependent granule
      convergence to the MTOC and granule and MTOC polarization to the synapse and
      suppressed NK cell killing of Cryptococcus. In contrast, Eg5-kinesin was
      dispensable for tumor killing. This reveals an alternative mechanism of MTOC
      repositioning and granule polarization, not used in tumor cytotoxicity, in which
      Eg5-kinesin is required to initiate granule movement, leading to microbial
      killing.

PMID- 30208326
TI  - TLR Crosstalk Activates LRP1 to Recruit Rab8a and PI3Kgamma for Suppression of
      Inflammatory Responses.
AB  - The multi-ligand endocytic receptor, low-density lipoprotein-receptor-related
      protein 1 (LRP1), has anti-inflammatory roles in disease. Here, we reveal that
      pathogen-activated Toll-like receptors (TLRs) activate LRP1 in human and mouse
      primary macrophages, resulting in phosphorylation of LRP1 at Y4507. In turn, this
      allows LRP1 to activate and recruit the guanosine triphosphatase (GTPase), Rab8a,
      with p110gamma/p101 as its phosphatidylinositol 3-kinase (PI3K) effector complex.
      PI3Kgamma is a known regulator of TLR signaling and macrophage reprogramming.
      LRP1 coincides with Rab8a at signaling sites on macropinosomal membranes. In LRP1
      deficient cells, TLR-induced Rab8 activation is abolished. CRISPR-mediated
      knockout of LRP1 in macrophages alters Akt/mTOR signaling and produces a pro
      inflammatory bias in cytokine outputs, mimicking the Rab8a knockout and PI3Kgamma
      null phenotype. Thus, TLR-LRP1 crosstalk activates the Rab8a/PI3Kgamma complex
      for reprogramming macrophages, revealing this as a key mechanism through which
      LRP1 helps to suppress inflammation.

PMID- 30208329
TI  - Decoding the Regulatory Logic of the Drosophila Male Stem Cell System.
AB  - The niche critically controls stem cell behavior, but its regulatory input at the
      whole-genome level is poorly understood. We elucidated transcriptional programs
      of the somatic and germline lineages in the Drosophila testis and genome-wide
      binding profiles of Zfh-1 and Abd-A expressed in somatic support cells and
      crucial for fate acquisition of both cell lineages. We identified key roles of
      nucleoporins and V-ATPase proton pumps and demonstrate their importance in
      controlling germline development from the support side. To make our dataset
      publicly available, we generated an interactive analysis tool, which uncovered
      conserved core genes of adult stem cells across species boundaries. We tested the
      functional relevance of these genes in the Drosophila testis and intestine and
      found a high frequency of stem cell defects. In summary, our dataset and
      interactive platform represent versatile tools for identifying gene networks
      active in diverse stem cell types.

PMID- 30208327
TI  - STIM1 and STIM2 Mediate Cancer-Induced Inflammation in T Cell Acute Lymphoblastic
      Leukemia.
AB  - T cell acute lymphoblastic leukemia (T-ALL) is commonly associated with
      activating mutations in the NOTCH1 pathway. Recent reports have shown a link
      between NOTCH1 signaling and intracellular Ca2+ homeostasis in T-ALL. Here, we
      investigate the role of store-operated Ca2+ entry (SOCE) mediated by the Ca2+
      channel ORAI1 and its activators STIM1 and STIM2 in T-ALL. Deletion of STIM1 and
      STIM2 in leukemic cells abolishes SOCE and significantly prolongs the survival of
      mice in a NOTCH1-dependent model of T-ALL. The survival advantage is unrelated to
      the leukemic cell burden but is associated with the SOCE-dependent ability of
      malignant T lymphoblasts to cause inflammation in leukemia-infiltrated organs.
      Mice with STIM1/STIM2-deficient T-ALL show a markedly reduced necroinflammatory
      response in leukemia-infiltrated organs and downregulation of signaling pathways
      previously linked to cancer-induced inflammation. Our study shows that leukemic T
      lymphoblasts cause inflammation of leukemia-infiltrated organs that is dependent
      on SOCE.

PMID- 30208328
TI  - Overcoming the Cost of Positive Autoregulation by Accelerating the Response with
      a Coupled Negative Feedback.
AB  - A fundamental trade-off between rapid response and optimal expression of genes
      below cytotoxic levels exists for many signaling circuits, particularly for
      positively autoregulated systems with an inherent response delay. Here, we
      describe a regulatory scheme in the E. coli PhoB-PhoR two-component system, which
      overcomes the cost of positive feedback and achieves both fast and optimal steady
      state response for maximal fitness across different environments. Quantitation of
      the cellular activities enables accurate modeling of the response dynamics to
      describe how requirements for optimal protein concentrations place limits on
      response speed. An observed fast response that exceeds the limit led to the
      prediction and discovery of a coupled negative autoregulation, which allows fast
      gene expression without increasing steady-state levels. We demonstrate the
      fitness advantages for the coupled feedbacks in both dynamic and stable
      environments. Such regulatory schemes offer great flexibility for accurate
      control of gene expression levels and dynamics upon environmental changes.

PMID- 30208330
TI  - Upregulated microRNA-146a expression induced by granulocyte colony-stimulating
      factor enhanced low-dosage chemotherapy response in aged acute myeloid leukemia
      patients.
AB  - The selection of chemotherapy regimen for elderly patients with acute myeloid
      leukemia (AML) remains challenging. Here, we report that granulocyte colony
      stimulating factor (G-CSF) upregulates the expression of microRNA (miR)-146a in a
      nuclear factor kappaB-dependent manner, leading to direct decreases in the
      expression of the target proteins CXCR4 and Smad4 in AML cells in vitro. The
      reduction in CXCR4 expression suppressed the migration abilities of leukemia
      cells. Downregulation of Smad4 promoted cell cycle entry in leukemia cells.
      Furthermore, an increase in apoptosis was observed when leukemia cells were
      treated sequentially with G-CSF and cytosine arabinoside in vitro. These findings
      suggest that G-CSF treatment may disrupt the protection of bone marrow niches
      from leukemia cells. In a review of data from 78 cases of primary AML, we found
      that a high miR-146a expression and/or upregulation of this miRNA during G-CSF
      priming chemotherapy was predictive of better clinical outcomes. Our findings
      suggest that miR-146a may be a novel biomarker for evaluating the clinical
      prognosis and treatment effects of a G-CSF priming protocol in elderly patients
      with AML.

PMID- 30208331
TI  - Heterologous expression of a broad-spectrum chimeric antimicrobial peptide in
      Lactococcus lactis: Its safety and molecular modeling evaluation.
AB  - Over the last decade, global increase in antibiotic consumption is a major
      concern in the word. Antimicrobial peptides (AMPs) known as potential alternative
      and were considered as a safe antimicrobial agent. However, current approaches
      for production and purification of AMPs are costly and time-consuming. Here we
      show that heterologous expression of a chimeric peptide was successfully
      developed in Lactococcus lactis as a safe and cost-effective recombinant protein
      expression platform. Minimum inhibitory concentrations (MICs) of His-tag purified
      peptide was determined against a broad spectrum of human pathogenic bacteria
      consistence of Gram-positive, Gram-negative and resistance strains in deferent
      range from 7.24 +/- 0.4 to 156.24 +/- 3.0 MUg/mL. Furthermore, our results showed
      that the peptide was not toxic to HEK and HeLa cells and even at concentrations
      as high as 250 MUg/mL exhibited minimal hemolysis against RBCs. Additional
      characteristics such as thermal, protease and 50% human plasma stability were
      determined for cLFchimera. Molecular modeling analysis demonstrated that fusion
      of His-tag to the C-terminal of chimeric peptide increased peptide stability
      during 10 ns simulation in water. Overall, the chimeric peptide has a
      considerable antibacterial activity with low hemolysis, low or none in toxicity
      and good temperature resistance and also high stability in serum. We anticipate
      the established expression system could be developed and used more effectively in
      probiotic strains in future studies.

PMID- 30208332
TI  - Regional mechanical and biochemical properties of the porcine cortical meninges.
AB  - The meninges are pivotal in protecting the brain against traumatic brain injury
      (TBI), an ongoing issue in most mainstream sports. Improved understanding of TBI
      biomechanics and pathophysiology is desirable to improve preventative measures,
      such as protective helmets, and advance our TBI diagnostic/prognostic
      capabilities. This study mechanically characterised the porcine meninges by
      performing uniaxial tensile testing on the dura mater (DM) tissue adjacent to the
      frontal, parietal, temporal, and occipital lobes of the cerebellum and superior
      sagittal sinus region of the DM. Mechanical characterisation revealed a
      significantly higher elastic modulus for the superior sagittal sinus region when
      compared to other regions in the DM. The superior sagittal sinus and parietal
      regions of the DM also displayed local mechanical anisotropy. Further, fatigue
      was noted in the DM following ten preconditioning cycles, which could have
      important implications in the context of repetitive TBI. To further understand
      differences in regional mechanical properties, regional variations in protein
      content (collagen I, collagen III, fibronectin and elastin) were examined by
      immunoblot analysis. The superior sagittal sinus was found to have significantly
      higher collagen I, elastin, and fibronectin content. The frontal region was also
      identified to have significantly higher collagen I and fibronectin content while
      the temporal region had increased elastin and fibronectin content. Regional
      differences in the mechanical and biochemical properties along with regional
      tissue thickness differences within the DM reveal that the tissue is a non
      homogeneous structure. In particular, the potentially influential role of the
      superior sagittal sinus in TBI biomechanics warrants further investigation.
      STATEMENT OF SIGNIFICANCE: This study addresses the lack of regional mechanical
      analysis of the cortical meninges, particularly the dura mater (DM), with
      accompanying biochemical analysis. To mechanically characterise the stiffness of
      the DM by region, uniaxial tensile testing was carried out on the DM tissue
      adjacent to the frontal, parietal, temporal and occipital lobes along with the DM
      tissue associated with the superior sagittal sinus. To the best of the authors'
      knowledge, the work presented here identifies, for the first time, the
      heterogeneous nature of the DM's mechanical stiffness by region. In particular,
      this study identifies the significant difference in the stiffness of the DM
      tissue associated with the superior sagittal sinus when compared to the other DM
      regions. Constitutive modelling was carried out on the regional mechanical
      testing data for implementation in Finite Element models with improved
      biofidelity. This work also presents the first biochemical analysis of the
      collagen I and III, elastin, and fibronectin content within DM tissue by region,
      providing useful insights into the accompanying macro-scale biomechanical data.

PMID- 30208333
TI  - Generation of Fcabs targeting human and murine LAG-3 as building blocks for novel
      bispecific antibody therapeutics.
AB  - The immunoglobulin superfamily protein lymphocyte-activation gene 3 (LAG-3)
      participates in immune suppression and has been identified as a suitable target
      for cancer therapies. In order to generate bispecific antibodies targeting LAG-3,
      Fcabs (Fc-region with antigen binding) targeting human and murine LAG-3 were
      generated from phage libraries. These Fcabs bind to LAG-3, inhibiting its
      interaction with MHC class II, and induce IL-2 production in a T cell assay.
      Bispecific antibodies, known as mAb2, were produced by replacing the Fc region of
      a monoclonal antibody with Fcab sequences in the CH3 domain. mAb2 containing anti
      LAG-3 Fcabs have mAb-like biophysical characteristics and retain LAG-3 binding
      and functional activity. mAb2 can thus be generated using multiple Fabs to
      investigate bispecific parings and develop novel therapeutics.

PMID- 30208334
TI  - Evolutionary history of Mo25 gene in plants, a component of RAM/MOR signaling
      network.
AB  - Change in cell morphogenesis is an important feature for proper development of
      eukaryotes. It is necessary for cell polarity and asymmetry and is essential for
      asymmetric cell division. RAM/MOR is a conserved signaling network that
      coordinates cell polarity determinants important for asymmetric cell division and
      cell polarity establishment. Mo25 is a scaffold protein that acts as a master
      regulator of the germinal center kinase (GCK) which triggers the downstream
      signaling of this network. Little is known about RAM/MOR network or Mo25 protein
      homologs in plants. Here, we provide a glimpse of the evolutionary gene history
      of Mo25 in green plants. Our data showed that a duplication of Mo25 occurred at
      the basis of land plants (Embryophyta), forming the groups Mo25A and Mo25B.
      Further duplication events occurred in other plant lineages and one subgroup of
      sequences seemed to be rapidly diverging. This subgroup contained an A. thaliana
      paralog (AtMo25-1) which lacks intron and is expressed in a similar fashion of
      retrogenes (i.e. low expression levels and narrow expression breadth), suggesting
      that this paralog was duplicated by retroposition. We also showed that all AtMo25
      proteins are structurally similar to each other and to the human homolog,
      although differences in residues in the interface between human Mo25 and MST3 are
      observed in the A. thaliana homologs. Expression profile of AtMo25 homologs
      suggest that they are required at different developmental contexts, possibly
      interacting with different partners. Finally, we discuss whether Mo25 duplication
      in Embryophyta could be an evolutionary novelty important for the terrestrial
      environment conquest and whether the duplicated paralogs are undergoing neo- or
      subfunctionalization.

PMID- 30208336
TI  - Dynamic Top-down Configuration by the Core Control System During Working Memory.
AB  - The central executive system (CES) may be the most fundamental yet least
      understood component of working memory. There is an ongoing debate about which
      brain regions underlie the top-down regulation of CES during working memory
      tasks. The neural substrates and regulatory mechanisms of CES remain
      controversial partly because few previous studies have been focused on
      comprehensive activation and deactivation joint analysis on all systems involved
      in all working memory stages, which have shown increasing importance in depicting
      the neural configuration of working memory. To address these questions, we
      conducted a functional magnetic resonance imaging study using a comprehensive
      activation-deactivation-behavior joint analysis to examine the dynamics of a set
      of cortical systems in healthy subjects performing a modified Sternberg working
      memory task which was designed to push the subjects to their limit in working
      memory and to introduce strong demands for regulation by CES. We assessed brain
      activity during various working memory stages using general linear model and
      single trial-stage estimation, and examined the relationship between the single
      trial-stage activity and behavioral performance. We identified constant
      activation in the dorsal anterior cingulate cortexand anterior insula in all
      working memory stages and its relationship with performance, which indicate the
      CES's neural basis. We also identified dynamic configuration of multiple
      downstream systems in different working memory stages, which indicates the
      regulation mechanism of CES.

PMID- 30208335
TI  - Phthalate exposure and odds of bacterial vaginosis among U.S. reproductive-aged
      women, NHANES 2001-2004.
AB  - Endocrine-disrupting chemicals, such as phthalates, are an unexamined potential
      risk factor for bacterial vaginosis (BV) and warrant investigation because
      hormones affect BV. We examined the association between phthalate exposure and BV
      in the National Health and Nutrition Examination Survey, 2001-2004. BV outcomes
      were defined as intermediate (Nugent score of 4-6) and positive (7-10). Phthalate
      metabolites, including monoethyl phthalate (MEP), mono-n-butyl phthalate (MnBP),
      and di(2-ethylhexyl) phthalate (DEHP) metabolites, were measured in urine. Among
      854 women with complete data, multinomial logistic regression revealed that
      concentrations of MnBP (Q4 vs. Q1 OR = 3.01, 95% CI 1.76-5.15, p-trend <0.001)
      and SigmaDEHP metabolites (Q4 OR = 2.55, 95% CI 1.45-4.47, p-trend = 0.03) were
      associated with Nugent-score BV, although only MnBP was significant after
      adjustment for confounders. Associations were null after adjustment for urinary
      creatinine (MnBP Q4 OR = 1.11, 95% CI 0.63-1.96; SigmaDEHP Q4 OR = 0.72, 95% CI
      0.37-1.39). Future work should further examine these relationships using direct
      measurements of intravaginal phthalates exposures.

PMID- 30208337
TI  - Blocking of Dendrodendritic Inhibition Unleashes Widely Spread Lateral
      Propagation of Odor-evoked Activity in the Mouse Olfactory Bulb.
AB  - The olfactory circuitry in mice involves a well-characterized, vertical receptor
      type-specific organization, but the localized inhibitory effect from granule
      cells on action potentials that propagate laterally in secondary dendrites of
      mitral cell remains open to debate. To understand the functional dynamics of the
      lateral (horizontal) circuits, we analyzed odor-induced signaling using
      transgenic mice expressing a genetically encoded Ca2+ indicator specifically in
      mitral/tufted and some juxtaglomerular cells. Optical imaging of the dorsal
      olfactory bulb (dOB) revealed specific patterns of glomerular activation in
      response to odor presentation or direct electric stimulation of the olfactory
      nerve (ON). Application of a mixture of ionotropic and metabotropic glutamate
      receptor antagonists onto the exposed dOB completely abolished the responses to
      direct stimulation of the ON as well as discrete odor-evoked glomerular responses
      patterns, while a spatially more widespread response component increased and
      expanded into previously nonresponsive regions. To test whether the widespread
      odor response component represented signal propagation along mitral cell
      secondary dendrites, an NMDA receptor antagonist alone was applied to the dOB and
      was found to also increase and expand odor-evoked response patterns. Finally,
      with dOB excitatory synaptic transmission completely blocked, application of 1 mM
      muscimol (a GABAA receptor agonist) to a circumscribed volume in the deep
      external plexiform layer (EPL) induced an odor non-responsive area. These results
      indicate that odor stimulation can activate olfactory reciprocal synapses and
      control lateral interactions among olfactory glomerular modules along a wide
      range of mitral cell secondary dendrites by modulating the inhibitory effect from
      granule cells.

PMID- 30208338
TI  - Serotonin contribution to cardiac valve degeneration: new insights for novel
      therapies?
AB  - Heart valve disease (HVD) is a complex entity made by different pathological
      processes that ultimately lead to the abnormal structure and disorganization of
      extracellular matrix proteins resulting to dysfunction of the leaflets. At its
      final evolutionary step, treatments are limited to the percutaneous or surgical
      valve replacement, whatever the original cause of the degeneration. Understanding
      early molecular mechanisms that regulate valve interstitial cells remodeling and
      disease progression is challenging and could pave the way for future drugs aiming
      to prevent and/or reverse the process. Some valve degenerative processes such as
      the carcinoid heart disease, drug-induced valvulopathy and degenerative mitral
      valve disease in small-breed dogs are clearly linked to serotonin. The carcinoid
      heart is typically characterized by a right-sided valve dysfunction, observed in
      patients with carcinoid tumors developed from serotonin-producing gut
      enterochromaffin cells. Fenfluramine or ergot derivatives were linked to mitral
      and aortic valve dysfunction and share in common the pharmacological property of
      being 5-HT2B receptor agonists. Finally, some small-breed dogs, such as the
      Cavalier King Charles Spaniel are highly prone to degenerative mitral valve
      disease with a prevalence of 40% at 4 years-old, 70% at 7 years-old and 100% in
      10-year-old animals. This degeneration has been linked to high serum serotonin, 5
      HT2B receptor overexpression and SERT downregulation. Through the comprehension
      of serotonergic mechanisms involved into these specific situations, new
      therapeutic approaches could be extended to HVD in general. More recently, a
      serotonin dependent/ receptor independent mechanism has been suggested in
      congenital mitral valve prolapse through the filamin-A serotonylation. This
      review summarizes clinical and molecular mechanisms linking the serotonergic
      system and heart valve disease, opening the way for future pharmacological
      research in the field.

PMID- 30208339
TI  - Immediate stimulus repetition abolishes stimulus expectation and surprise effects
      in fast periodic visual oddball designs.
AB  - Oddball designs are widely used to investigate the sensitivity of the visual
      system to statistical regularities in sensory environments. However, the
      underlying mechanisms that give rise to visual mismatch responses remain unknown.
      Much research has focused on identifying separable, additive effects of stimulus
      repetition and stimulus appearance probability (expectation/surprise) but
      findings from non-oddball designs indicate that these effects also interact. We
      adapted the fast periodic visual stimulation (FPVS) unfamiliar face identity
      oddball design (Liu-Shuang et al., 2014) to test for both additive and
      interactive effects of stimulus repetition and stimulus expectation. In two
      experiments, a given face identity was presented at a 6 Hz periodic rate; a
      different identity face (the oddball) appeared as every 7th image in the sequence
      (i.e., at 0.857 Hz). Electroencephalographic (EEG) activity was recorded during
      these stimulation sequences. In Experiment 1, we tested for surprise responses
      evoked by unexpected face image repetitions by replacing 10% of the commonly
      presented oddball faces with exact repetitions of the base rate face identity
      image. In Experiment 2, immediately repeated or unrepeated face identity oddballs
      were presented in high and low presentation probability contexts (i.e., expected
      or surprising contexts), allowing assessment of expectation effects on responses
      to both repeated and unrepeated stimuli. Across both experiments objective (i.e.,
      frequency-locked) visual mismatch responses driven by stimulus expectation were
      only found for oddball faces of a different identity to base rate faces (i.e.,
      unrepeated identity oddballs). Our results show that immediate stimulus
      repetition (i.e., repetition suppression) can reduce or abolish expectation
      effects as indexed by EEG responses in visual oddball designs.

PMID- 30208340
TI  - CCGD-ESCC: A Comprehensive Database for Genetic Variants Associated with
      Esophageal Squamous Cell Carcinoma in Chinese Population.
AB  - Esophageal squamous-cell carcinoma (ESCC) is one of the most lethal malignancies
      in the world and occurs at particularly higher frequency in China. While several
      genome-wide association studies (GWAS) of germline variants and whole-genome or
      whole-exome sequencing studies of somatic mutations in ESCC have been published,
      there is no comprehensive database publically available for this cancer. Here, we
      developed the Chinese Cancer Genomic Database-Esophageal Squamous Cell Carcinoma
      (CCGD-ESCC) database, which contains the associations of 69,593 single nucleotide
      polymorphisms (SNPs) with ESCC risk in 2022 cases and 2039 controls, survival
      time of 1006 ESCC patients (survival GWAS) and gene expression (expression
      quantitative trait loci, eQTL) in 94 ESCC patients. Moreover, this database also
      provides the associations between 8833 somatic mutations and survival time in 675
      ESCC patients. Our user-friendly database is a resource useful for biologists and
      oncologists not only in identifying the associations of genetic variants or
      somatic mutations with the development and progression of ESCC but also in
      studying the underlying mechanisms for tumorigenesis of the cancer. CCGD-ESCC is
      freely accessible at http://db.cbi.pku.edu.cn/ccgd/ESCCdb.

PMID- 30208341
TI  - An epigenetic perspective on tumorigenesis: Loss of cell identity, enhancer
      switching, and NamiRNA network.
AB  - Various tumorigenic theories have been proposed in the past century, which
      contribute to the prevention and treatment of cancer clinically. However, the
      underlying mechanisms of the initiation of cancer, drug resistance, neoplasm
      relapse, and metastasis are still challenging to be panoramically addressed.
      Based on the abundant evidence provided by others and us, we postulate that Tumor
      Initiated by Loss of Cell Identity (LOCI), which is an inevitable initiating
      event of tumorigenesis. As a result, normal cells are transformed into the
      cancerous cell. In this process, epigenetic regulatory program, especially
      NamiRNA (Nuclear activating miRNA)-enhancer-gene activation network, is vital for
      the cell identity. The disorganization of NamiRNA-enhancer-gene activation
      network is a causal predisposition to the cell identity loss, and the altered
      cell identity is stabilized by genetic variations of the NamiRNA-enhancer-gene
      activation network. Furthermore, the additional genetic or epigenetic abnormities
      confer those cells to carcinogenic characteristics, such as growth advantage over
      normal cells, and finally yield cancer. In this review, we literally explain our
      tumor imitation hypothesis based on the corresponding evidence, which will not
      only help to refresh our understanding of tumorigenesis but also bring benefits
      to developing "cell identity reversing" based therapies.

PMID- 30208342
TI  - The sole and combined effect of simvastatin and platelet rich fibrin as a filling
      material in induced bone defect in tibia of albino rats.
AB  - Statins like simvastatin (SIM) have demonstrated to have pleiotropic actions
      other than their conventional use as antilipidemic drugs. Also, nowadays natural
      scaffolds like platelets rich fibrin (PRF) showed promising results on bone
      regeneration. Aim This study compare the regenerative power of SIM and PRF added
      locally each as a sole filling material on induced bone defect and evaluate the
      combined effect using PRF loaded with SIM. MATERIALS AND METHODS: A critical size
      bone defect was induced in 48 male albino rats of average weight 150-200 g and
      were divided into 4 groups according to the filling material. Control, PRF, SIM,
      and SIM/PRF group. Each group was subdivided according to the sacrificing period
      into two subgroups (one and two-months postoperatively). Tibial specimens were
      evaluated histologically using masson trichrome (MT) special stain to detect
      areas of new bone formation, immunohistochemically using anti- BMP2 and anti
      VEGF, serum levels of Osteoprotegerin (OPG), RANKL, osteocalcin and alkaline
      phosphatase enzyme (ALP) were measured one and two months postoperatively using
      ELISA, Finally bone mineral density (BMD) at the bone defect area was analyzed
      using digital X-ray one and two-months postoperatively. RESULTS: The percentage
      of newly formed bone increased significantly in the three groups vs the control
      group with the highest significant increase (p < 0.001) in the SIM/PRF group one
      month postoperatively. Also, SIM/PRF group was the only group which showed
      significant bone maturation two-months postoperatively compared to the other
      groups. Immunohistochemical analysis showed significant increase in positively
      stained BMP-2 and VEGF expression (p < 0.001) in the three groups vs the control
      group with the highest significant increase (p < 0.001) in the SIM/PRF group.
      Serum bone anabolic markers increased significantly in the SIM and SIM/PRF
      groups. In contrast, RANKL serum level decreased significantly in the SIM and
      SIM/PRF group one month postoperatively with no significant decrease in the PRF
      group vs the control group. Digital X-ray results revealed the highest BMD
      percent change was found in the SIM/PRF group and showed complete bone healing
      two-months postoperatively.

PMID- 30208344
TI  - Improving the cardiometabolic health of people with psychosis: A protocol for a
      randomised controlled trial of the Physical Health Nurse Consultant service.
AB  - BACKGROUND: Over 690,000 Australians experience psychosis annually, significantly
      impacting cardiometabolic illness and healthcare costs. Current models of care
      are fragmented and a critical implementation gap exists regarding the delivery of
      coordinated physical healthcare for Australians with psychosis. OBJECTIVES: To
      describe a trial implementing a Physical Health Nurse Consultant (PHNC) role to
      coordinate physical health care in a community mental health setting.
      DESIGN/METHODS: In this 24-month, 2-group randomised controlled trial, 160 adults
      with psychosis will be randomised to usual care, or to the PHNC in addition to
      usual care. Using the Positive Cardiometabolic Health treatment framework and
      working in collaborative partnerships with consumers (consumer-led co-design),
      the PHNC will provide care coordination including referral to appropriate
      programmes or services based on the treatment framework, with the consumer.
      Burden of Disease risk factors will be collected according to Australian Bureau
      of Statistics' National Health Survey guidelines. Consumer experience will be
      assessed using the 'Access', 'Acceptability' and 'Shared Decision Making'
      dimensions of the Patient Experiences in Primary Healthcare Survey. Cost
      effectiveness will be modelled from Burden of Disease data using the Assessing
      Cost Effectiveness Prevention methodology. RESULTS: Data collection of two years
      duration will commence in late 2018. Preliminary findings are expected in
      December 2019. Primary outcomes will be the effect of the PHNC role on physical
      healthcare in community-based adults with psychosis. CONCLUSIONS: The PHNC is an
      innovative approach to physical health care for adults with psychosis which aims
      to meet the physical health needs of consumers by addressing barriers to physical
      health care.

PMID- 30208345
TI  - Phthalate exposure and childhood overweight and obesity: Urinary metabolomic
      evidence.
AB  - OBJECTIVE: Metabolomics may unravel global metabolic changes in response to
      environmental exposures and identify important biological pathways involved in
      the pathophysiology of childhood obesity. Phthalate has been considered an
      obesogen and contributing to overweight and obesity in children. The purpose of
      this study is to evaluate changes in urine metabolites in response to the
      environmental phthalate exposure among overweight or obese children, and to
      investigate the metabolic mechanisms involved in the obesogenic effect of
      phthalate on children at puberty. METHODS: Within the national Puberty Timing and
      Health Effects in Chinese Children (PTHEC) study, 69 overweight/obese children
      and 80 normal weight children were selected into the current study according to
      their puberty timing and WGOC (The Working Group for obesity in China)
      references. Urinary concentrations of six phthalate monoesters (MMP, MEP, MnBP,
      MEHP, MEOHP and MEHHP) were measured using API 2000 electrospray triple
      quadrupole mass spectrometer (ESIMS/MS). Metabolomic profiling of spot urine was
      performed using gas chromatography-mass spectrometry. Differentially expressed
      urinary metabolites associated with phthalate monoesters exposure were examined
      using orthogonal partial least square-discriminant analysis and multiple linear
      regression models. In addition, the candidate metabolites were regressed to
      obesity indices with multiple linear regression models and logistic regression
      models in all subjects. RESULTS: Compared with normal weight children, higher
      levels of MnBP were detected in urinary samples of children with overweight and
      obesity. After adjusting for confounders including chronological age, gender,
      puberty onset, daily energy intake and physical activity and socio-economic
      level, positive association remained between urinary MnBP concentration and
      childhood overweight/obesity [OR = 1.586, 95% CI:1.043,2.412]. We observed
      elevated MnBP concentration was significantly correlated with increased levels of
      monostearin, 1-monopalmitin, stearic acid, itaconic acid, glycerol 3-phosphate, 5
      methoxytryptamine, kyotorphin, 1-methylhydantoin, d-alanyl-d-alanine, pyrrole-2
      carboxylic acid, 3,4-Dihydroxyphenylglycol, and butyraldehyde. Meanwhile,
      increased MnBP concentration was also significantly correlated with decreased
      levels of lactate, glucose 6-phosphate, d-fructose 6-phosphate, palmitic acid, 4
      acetamidobutyric acid, l-glutamic acid, n-acetyl-l-phenylalanine, iminodiacetic
      acid, hydroxyproline, pipecolinic acid, l-ornithine, n-acetyl-l-glutamic acid,
      guanosine, cytosin, and (s)-mandelic acid in the normal weight subjects. The
      observations indicated that MnBP exposure was related to global urine metabolic
      abnormalities characterized by disrupting arginine and proline metabolism and
      increasing oxidative stress and fatty acid reesterification. Among the metabolic
      markers related to MnBP exposure, 1-methylhydantoin, pyrrole-2-carboxylic acid
      and monostearin were found to be positively correlated with obesity indices,
      while hydroxyproline, l-ornithine, and lactate were negatively associated with
      overweight/obesity in children. CONCLUSIONS: Our results suggested that the
      disrupted arginine and proline metabolism associated with phthalate exposure
      might contribute to the development of overweight and obesity in school-age
      children, providing insights into the pathophysiological changes and molecular
      mechanisms involved in childhood obesity.

PMID- 30208346
TI  - Nitrogen release and its influence on anammox bacteria during the decay of
      Potamogeton crispus with different values of initial debris biomass.
AB  - Aquatic macrophytes play a significant role in the nutrient cycle of freshwater
      ecosystems. However, nutrients from plant debris release into both sediments and
      overlying water if not timely harvested. To date, minimal information is
      available regarding nutrient release and its subsequent influences on bacterial
      communities with decaying debris. In this study, Potamogeton crispus was used as
      a model plant. Debris biomass levels of 0 g (control, J-CK), 10 g dry weight (DW)
      (100 g DW/m2, J-10 g), 40 g DW (400 g DW/m2, J-40 g) and 80 g DW (800 g DW/m2, J
      80 g) were used to simulate the different biomass densities of P. crispus in
      field. The physicochemical parameters of overlying water and sediment samples
      were analysed. The community composition of anammox bacteria in the sediment was
      also analysed using 16S rRNA genes as markers. The results showed that dissolved
      oxygen and pH dramatically decreased, whereas total nitrogen (TN) and NH4+-N
      concentrations increased in the overlying water in the initial stage of P.
      crispus decomposition. However, NO3--N concentration changes in the overlying
      water were more complicated. The concentrations of organic matter, TN and NH4+-N
      in the sediment all increased, but the rate of increase varied among the groups
      with different initial biomass levels, indicating that these physicochemical
      properties in sediment are significantly affected by debris biomass level and
      decay time. In addition, the order of anammox bacteria abundance was J-40 g > J
      CK > J-80 g > J-10 g. Moreover, the community structure of anammox bacteria were
      simpler compared to that of J-CK as debris biomass level increased. The results
      demonstrate that P. crispus debris decomposition could affect the ecological
      distribution of anammox bacteria. Such influence clearly varies with varying
      amounts of P. crispus biomass debris. This information could be useful for the
      management of aquatic macrophytes in freshwater ecosystems.

PMID- 30208343
TI  - Rationale and design of technology assisted stepped collaborative care
      intervention to improve patient-centered outcomes in hemodialysis patients
      (TACcare trial).
AB  - Most hemodialysis (HD) patients experience symptoms of depression, pain and
      fatigue that impair their health-related quality of life (HRQOL) significantly.
      These symptoms are associated with increased hospitalization and mortality,
      mediated by behavioral factors (e.g. non-adherence to medication and dialysis)
      and biological factors (e.g. inflammatory cytokines). Prior interventions to
      alleviate symptoms and improve HRQOL showed limited effectiveness in HD patients
      and their effect on bio-behavioral mediators is lacking evidence. It is
      imperative to improve patient-centered dialysis care and to address call from
      Kidney Disease Improving Global Outcomes (KDIGO) guidelines for integration of
      symptom assessment and management in routine HD-care. Technology-Assisted stepped
      Collaborative Care (TACcare) is a multi-center randomized controlled trial (RCT)
      of 150 diverse HD patients from Pennsylvania and New Mexico, designed to compare
      the effectiveness of a 12-week stepped collaborative care intervention (cognitive
      behavioral therapy, CBT) with an attention control arm of technology-delivered
      health education. Collaborative care provides an integrated multi-disciplinary
      structured management plan. Furthermore, a stepped approach to pharmacotherapy
      and/or CBT allows for individualization of treatment according to patients'
      clinical status, preferences and treatment response. To simplify the delivery of
      CBT and to minimize patient and provider burden, we will use live video
      conferencing with patients in dialysis units. We will examine the effect of these
      interventions on patient symptoms, HRQOL, treatment adherence and inflammatory
      biomarkers. This RCT tests a readily implementable intervention that can be
      integrated in routine HD-care and will generate novel and meaningful insights on
      strategies to alleviate common symptoms and improve HRQOL in HD.

PMID- 30208347
TI  - Characteristics of indoor air pollution and estimation of respiratory dosage
      under varied fuel-type and kitchen-type in the rural areas of Telangana state in
      India.
AB  - Indoor Air Pollution (IAP) is one of the top environmental risks in developing
      countries including India, with more than a million deaths annually,
      predominantly through Particulate Matter (PM) exposure. The current study deals
      with the measurement of PM concentrations in rural households under varied fuel
      and kitchen-types, evaluation of the indoor air pollution (IAP) characteristics
      and estimation of respiratory dosage for the different subjects (women, young
      children and the elderly). Monitoring of particulate matter (PM) was carried out
      during summer, monsoon and winter season with biomass, LPG and combine of biomass
      and LPG being used as fuel for cooking. Furthermore, different types of indoor
      kitchens (with partition and without partition) and outdoor kitchens (separate
      enclose kitchen and open kitchen) were also considered as kitchen type along with
      fuel are two crucial factors contributing to IAP. Deposition fractions were
      calculated using Multiple Particle Path Dosimetry (MPPD) to study the deposition
      patterns in different parts of the human respiratory tract (HRT) - head,
      tracheobronchial and pulmonary for women, young children and the elderly people.
      Dosage of particulate matter was calculated by inputting the recorded PM
      measurements, a comparison made for biomass-LPG and dosage intensification due to
      the kitchen-type presented. While the biomass households exhibited high levels of
      dosage (1181.4 to 5891.7 MUg) against the LPG households (89.9 to 811.2 MUg), the
      indoor kitchen types exhibited a maximum intensification of 10.6 times than
      outdoor kitchens with the same fuel. This study not only establishes the IAP
      characteristics but also quantifies the role of fuel-type and kitchen-type in
      IAP. The study also indicates various measures that could be deployed to reduce
      dosage and thus minimize the health risks.

PMID- 30208348
TI  - Changes in nitrogen related functional genes along soil pH, C and nutrient
      gradients in the charosphere.
AB  - The interface between biochar and soil differs from both the bulk soil and the
      biochar itself, and has been termed the "charosphere". However, a complete
      definition of the charosphere, including aspects of size, properties, functional
      reach and effects on soil processes, is still required. In this study, the
      distributions of functional genes related to the soil N cycle within the
      charosphere were investigated over a multi-sectional gradient. We found that
      concentrations of dissolved organic carbon (DOC), available phosphorus and
      exchangeable cations (Ca2+, Mg2+, K+) increased with proximity to the biochar
      surface (termed the 'near charosphere'). Similarly, the abundance of bacterial
      amoA was greater in the near charosphere, while archaeal amoA abundance was
      relatively homogenous. This taxonomic asymmetry resulted in a shift in the
      predominant ammonia-oxidizers from ammonia-oxidizing bacteria (AOB) to ammonia
      oxidizing archaea (AOA) in the far charosphere. This was associated with other
      factors such as decreasing pH and carbon availability with increasing distance
      from the biochar. Moreover, the ratio of nosZ/(nirS + nirK) genes also showed
      functionally asymmetry in the charosphere: increasing with increasing distance
      from the biochar. This is the first study to map spatial distributions of a set
      functional genes related to soil N cycling in the soil around biochar. This
      exploration into the underlying heterogeneity of biochar-affected mechanisms of N
      transformation provides new insight into the functional geometry of the
      charosphere.

PMID- 30208350
TI  - Cognitive predictors of reactive and proactive aggression in a forensic sample: A
      comparison with a non-clinical sample.
AB  - This study aimed at examining cognitive predictors of reactive and proactive
      aggression in a forensic-psychiatric (n = 80) and a non-clinical sample (n = 98;
      Brugman et al., 2015). Three different cognitive predictors were incorporated:
      (1) attentional bias towards aggressive stimuli (measured with Emotional Stroop
      task) and towards angry faces (measured with a visual search task); (2)
      interpretation biases (measured with Aggressive Interpretative Bias Task (AIBT)
      and a vignette task), and (3) implicit self-aggression association (measured with
      a Single-Target Implicit Association Task). To measure aggression, the Reactive
      Proactive Aggression Questionnaire (RPQ) and the Taylor Aggression Paradigm (TAP)
      were used. An automatic self-aggression association positively predicted
      proactive aggressive behavior on the TAP in both samples. Furthermore, this self
      aggression association predicted, increased self-reported proactive aggression
      (RPQ) in the forensic sample only. Pain, injury, and danger interpretations
      reported on the vignettes, negatively predicted self-reported proactive
      aggression in both samples. A stronger aggressive interpretation bias on the AIBT
      predicted more reactive aggressive behavior (TAP) in the non-clinical sample
      only. Taken together, findings show both common and distinct mechanisms in
      reactively vs. proactively driven aggressive behavior.

PMID- 30208349
TI  - Stigma, gender dysphoria, and nonsuicidal self-injury in a community sample of
      transgender individuals.
AB  - We investigated rates of nonsuicidal self-injury (NSSI) and correlates of past
      year NSSI among transgender people to better understand factors contributing to
      this health disparity. A community-based sample of 332 transgender people
      participated in quantitative in-person interviews. The mean age of participants
      was 34.56 years (SD = 13.78, range = 16-87). The sample was evenly divided
      between transfeminine spectrum (50.3%) and transmasculine spectrum identities
      (49.7%) and was diverse in race/ethnicity. We evaluated associations between
      sociodemographic characteristics, stigma, hypothesized resilience factors, and
      identity variables with past-year NSSI. 53.3% of participants reported ever
      having self-injured in their lifetime. Past-year NSSI was reported by 22.3% of
      the sample and did not significantly differ based on gender identity. In logistic
      regression models, past-year NSSI was associated with younger age and felt stigma
      (perceived or anticipated rejection), but not enacted stigma (actual experiences
      of discrimination), and with gender dysphoria. Efforts to address the high rates
      of NSSI among transgender people should aim to reduce felt stigma and gender
      dysphoria, and promote transgender congruence. Future research using a
      developmental approach to assess variations in NSSI across the life course and in
      relation to transgender identity development may illuminate additional processes
      that affect NSSI in this population.

PMID- 30208351
TI  - Epigenetic age analysis of brain in major depressive disorder.
AB  - A large body of evidence indicates major depressive disorder (MDD) associated
      with biological aging acceleration. In this study, we aim to assess epigenetic
      aging in different prefrontal sub-regions and cell types from postmortem tissues
      in MDD by using two public methylation datasets (subjects are 40 and 58
      respectively). Results showed that brain epigenetic age has a strong correlation
      with chronological age in both datasets. However, there are no significant
      differences in epigenetic aging acceleration between MDD and controls in all
      prefrontal sub-regions and cell types. In conclusion, this study provides
      evidence against epigenetic aging acceleration in the brain in MDD.

PMID- 30208352
TI  - Empathy and altruistic behavior in antisocial violent offenders with psychopathic
      traits.
AB  - Deficiencies in empathic functioning are considered a core characteristic of
      violent behavior. Enhancing empathy in aggressive populations may thus represent
      a promising intervention target. Hence, the aims of the present work were two
      fold: First, we wanted to thoroughly assess empathic competencies and second, we
      aimed to investigate effects of an empathy induction on experienced empathy
      levels and prosocial behavior in a sample of violent offenders relative to
      matched controls. Empathy was assessed using both self-report as well as
      objective measures. For the empathy induction, participants were presented with
      empathy inducing and control videos. To assess the effects of the empathy
      induction on behavior, participants played a dictator game indicative of
      prosocial behavior after every video. Violent offenders showed no systematic
      impairment in empathy measures. Despite lower shares in the dictator game across
      conditions, the empathy induction led to a substantial increase in prosocial
      behavior in both groups. Importantly, high psychopathy scores were distinctively
      associated with lower self-reported empathy levels, an attenuated affective
      responsiveness to the empathy induction, and less altruistic behavior. Treatment
      programs aiming to improve empathy should take individual characteristics into
      account and may be applied to distinctive subgroups rather than to violent
      offenders per se.

PMID- 30208353
TI  - Critical Role of Estrogen Receptor Alpha O-Glycosylation by N
      Acetylgalactosaminyltransferase 6 (GALNT6) in Its Nuclear Localization in Breast
      Cancer Cells.
AB  - Alteration of protein O-glycosylation in various human cancers including breast
      cancer is well known, but molecular roles of their aberrant glycosylations on
      cancer have not been fully understood. We previously reported critical roles of
      polypeptide N-acetylgalactosaminyltransferase 6 (GALNT6 or GalNAc-T6) that was
      upregulated in a great majority of breast cancer tissues. Here we further report
      O-glycosylation of estrogen receptor alpha (ER-alpha) by GALNT6 and the
      significant role of its nuclear localization in breast cancer cells. Knockdown of
      GALNT6 expression in two breast cancer cell lines, T47D and MCF7, in which both
      ER-alpha and GALNT6 were highly expressed, by small interfering RNA could
      significantly attenuate expression of ER-alpha. Immunocytochemical analysis
      clearly demonstrated the drastic decrease of ER-alpha protein in the nucleus of
      these cancer cells. Accordingly, the downstream genes of the ER-alpha pathway
      such as MYC, CCND1, and CTSD were significantly downregulated. We confirmed
      GALNT6-dependent ER-alpha O-glycosylation and identified O-glycosylation of S573
      in an F domain of ER-alpha by GALNT6 through LC-MS/MS analysis. We also obtained
      evidences showing that the glycosylation of ER-alpha at S573 by GALNT6 is
      essential for protein stability and nuclear localization of ER-alpha in breast
      cancer cells. Furthermore, we designed cell membrane-permeable peptides including
      the O-glycosylation site and found a significant decrease of the cell viability
      of breast cancer cells by treatment of these peptides in a GALNT6 expression
      dependent manner. Our study suggests that targeting the GALNT6 enzymatic activity
      as well as the GALNT6/ER-alpha interaction could be a promising therapeutic
      approach to ER-alpha-positive breast cancer patients.

PMID- 30208354
TI  - Cell competition in development: information from flies and vertebrates.
AB  - Cell competition is a biological mechanism conserved from Drosophila to
      vertebrates wherein neighboring cells compare their relative fitness status
      resulting in the elimination of less fit cells by those with higher fitness. This
      is an active process that is essential for embryonic and organ development,
      tissue homeostasis, delay of ageing and in various disease models such as cancer.
      Recent research is beginning to unravel the various mechanisms of cell
      competition and the sensing of fitness status. Fitness fingerprints, death
      receptors, mechanical cell competition and a set of unknown genetic or signaling
      pathways are emerging as important pathways governing the mechanisms for cell to
      compare their relative fitness levels. In this review we are providing an account
      of recent advances which help summarize the mechanisms of operation and growing
      role of cell competition in regulation of oncogenesis in vertebrates.

PMID- 30208355
TI  - Algorithms for left atrial wall segmentation and thickness - Evaluation on an
      open-source CT and MRI image database.
AB  - Structural changes to the wall of the left atrium are known to occur with
      conditions that predispose to Atrial fibrillation. Imaging studies have
      demonstrated that these changes may be detected non-invasively. An important
      indicator of this structural change is the wall's thickness. Present studies have
      commonly measured the wall thickness at few discrete locations. Dense
      measurements with computer algorithms may be possible on cardiac scans of
      Computed Tomography (CT) and Magnetic Resonance Imaging (MRI). The task is
      challenging as the atrial wall is a thin tissue and the imaging resolution is a
      limiting factor. It is unclear how accurate algorithms may get and how they
      compare in this new emerging area. We approached this problem of comparability
      with the Segmentation of Left Atrial Wall for Thickness (SLAWT) challenge
      organised in conjunction with MICCAI 2016 conference. This manuscript presents
      the algorithms that had participated and evaluation strategies for comparing them
      on the challenge image database that is now open-source. The image database
      consisted of cardiac CT (n=10) and MRI (n=10) of healthy and diseased subjects. A
      total of 6 algorithms were evaluated with different metrics, with 3 algorithms in
      each modality. Segmentation of the wall with algorithms was found to be feasible
      in both modalities. There was generally a lack of accuracy in the algorithms and
      inter-rater differences showed that algorithms could do better. Benchmarks were
      determined and algorithms were ranked to allow future algorithms to be ranked
      alongside the state-of-the-art techniques presented in this work. A mean atlas
      was also constructed from both modalities to illustrate the variation in
      thickness within this small cohort.

PMID- 30208356
TI  - Automatic segmentation variability estimation with segmentation priors.
AB  - PURPOSE: Segmentations produced manually by experts or by algorithms are subject
      to variability, as they depend on many factors, e.g., the structure of interest,
      the resolution, contrast and quality of the images, and the expert experience or
      the algorithmic method. To properly assess the quality of these segmentations, it
      is thus essential to quantify their variability. However, obtaining reference
      variability ground truth requires several observers to manually delineate
      structures, which is time-consuming and impractical. METHODS: We describe a new
      comprehensive formal framework for segmentation evaluation and variability
      estimation without ground truth and a generic method for automatic segmentation
      variability estimation based on segmentation priors and multivariate sensitivity
      analysis. The method inputs the image scan and a user-validated segmentation of
      the structure of interest and uses predefined segmentation priors to compute a
      variability estimation around the given segmentation. The segmentation priors are
      combined with an integrator function whose sensitivity around the given
      segmentation is the segmentation variability. RESULTS: We validate our methods
      with two studies. The first study establishes the reference manual delineation
      variability. Eleven radiologists with varying levels of expertise manually
      delineated the contours of liver tumors, lung tumors, kidneys, and brain
      hematomas on 2,835 delineations from 18 CT scans. The relative delineation volume
      variability ranges are 51 [-24,+27]% for liver tumors, 56 [-25,+31]% for lung
      tumors, 25 [-12,+13]% for kidney contours, and 53 [-24,+29]% brain hematomas. The
      second study compares the estimated segmentation variability results to this
      reference data. The mean volume variability difference of the delineation is <6%,
      with a Dice similarity coefficient of >70% with respect to the mean manual
      delineation variability data. CONCLUSIONS: Reliable segmentation variability
      estimation with no ground truth enables the establishment of a proper observer
      variability reference. The segmentation variability should be taken into account
      when setting reference standards for clinical decisions based on volumetric
      measurements and when evaluating segmentation algorithms.

PMID- 30208357
TI  - Mass cultivation of Dunaliella salina in a flat plate photobioreactor and its
      effective harvesting.
AB  - Mass cultivation of Dunaliella salina was standardized in a flat plate
      photobioreactor followed by a vertical flat plate photobioreactor. Maximum
      biomass productivity (14.95 +/- 0.43 mgL-1d-1 dry cell weight) was achieved in
      the latter at inoculum concentration of OD680nm = 0.1, 100 umolm-2s-1 light
      illumination and 1.0 L min-1 aeration. Semicontinuous operation with varying KNO3
      and NaHCO3 concentrations resulted highest biomass productivity (17.85 +/- 0.55
      mgL-1d-1) at 0.50 mM NaHCO3 and 15 mM KNO3. However, maximum lipid (16.36 +/-
      1.18% dry cell weight) was achieved at 0.75 mM NaHCO3 and 10 mM KNO3.
      Flocculation studies employing potash alum, FeCl3.6H2O or pH showed harvesting
      efficiencies exceeding 90% in 0.75 mM potash alum or FeCl3.6H2O or pH 11, but
      they yielded low concentration factor (<5) and were detrimental (Fv/Fm < 0.50). A
      combination of 0.50 mM FeCl3.6H2O and pH 9 was found as most suitable
      flocculating strategy with maximum concentration factor (>14) and least damaging
      (Fv/Fm > 0.54).

PMID- 30208358
TI  - Assessing the feasibility of intranasal radiotracer administration for in brain
      PET imaging.
AB  - INTRODUCTION: The development of clinically useful tracers for PET imaging is
      enormously challenging and expensive. The intranasal (IN) route of administration
      is purported to be a viable route for delivering drugs to the brain but has, as
      yet, not been investigated for the delivery of PET tracers. If the intranasal
      (IN) pathway presents a viable option, it extends the PET imaging field by
      increasing the number of tracers available for human use. Here we report the
      results of a rodent study testing the feasibility of the IN route to administer
      radiotracers for brain PET imaging. METHODS: We used two different, well
      characterised, brain penetrant radiotracers, [18F]fluorodeoxyglucose ([18F]FDG)
      and [18F]fallypride, and aimed to evaluate the pharmacokinetics after
      administration of the tracers via the intranasal route, and contrast this to
      intravenous administration. Image acquisition was carried out after tracer
      administration and arterial blood samples were collected at different time
      intervals, centrifuged to extract plasma and gamma counted. We hypothesised that
      [brain region]:[plasma] ratios would be higher via the intranasal route as there
      are two inputs, one directly from the nose to the brain, and another from the
      peripheral circulation. To assess the feasibility of using this approach
      clinically, we used these data to estimate radiation dosimetry in humans.
      RESULTS: Contrary to our hypothesis, in case of both radiotracers, we did not see
      a higher ratio in the expected brain regions, except in the olfactory bulb, that
      is closest to the nose. It appears that the radiotracers move into the olfactory
      bulb region, but then do not progress further into other brain regions. Moreover,
      as the nasal cavity has a small surface area, the extrapolated dosimetry
      estimations for intranasal human imaging showed an unacceptably high level (15
      mSv/MBq) of cumulative skin radiation exposure. CONCLUSIONS: Therefore, although
      an attractive route for brain permeation, we conclude that the intranasal route
      would present difficulties due to non-specific signal and radiation dosimetry
      considerations for brain PET imaging.

PMID- 30208360
TI  - Heartbeat: Focus on hypertrophic cardiomyopathy.

PMID- 30208359
TI  - Androgen receptor expression inversely correlates with immune cell infiltration
      in human epidermal growth factor receptor 2-positive breast cancer.
AB  - INTRODUCTION: Although targeting human epidermal growth factor receptor 2 (HER2)
      is a meaningful treatment in HER2-positive breast cancer, ultimately resistance
      develops. Androgen receptor (AR) expression and immune cell infiltration are
      thought to be involved in trastuzumab response and may, therefore, be of interest
      as additional targets for therapy in HER2-positive breast cancer. AIM: To improve
      insights into the presence among AR expression, immune cell infiltration and
      HER2, we analysed HER2-positive breast tumours. METHODS: Primary tumours of 221
      patients treated with trastuzumab for metastatic disease were selected. HER2
      status was centrally confirmed. AR, T-cells (CD3 and CD8), programmed cell death
      protein 1 (PD-1) and PD-1 ligand 1 immunohistochemical staining and M2 tumour
      associated macrophages (TAMs; CD68 and CD163) immunofluorescence were performed.
      Tumour-infiltrating lymphocytes were evaluated by haematoxylin and eosin
      staining. RESULTS: Sufficient tumour material was available for 150 patients.
      Oestrogen receptor was expressed in 51.3% of the tumours and AR in 81.3% of the
      tumours. AR expression was inversely correlated with M2 TAM (Pearson's r = 
      0.361, P < 0.001), CD3+ (r = -0.199, P < 0.030) and CD8+ (r = -0.212, P < 0.021)
      T-cell infiltration. Clustering analysis showed high immune cell infiltration in
      AR low-expressing tumours, and low immune cell infiltration in AR-high expressing
      tumours. CONCLUSION: AR expression inversely correlates with immune cell
      infiltration in HER2-positive breast cancer.

PMID- 30208361
TI  - Hypertrophic cardiomyopathy and the potential influence of etomidate on
      postoperative outcomes.

PMID- 30208362
TI  - Hypertrophic cardiomyopathy and the potential influence of etomidate on
      postoperative outcomes.

PMID- 30208363
TI  - Classic Spotlight: Bacteroids-Views of an Enigmatic Bacterial State in Root
      Nodule Symbiosis through the Centuries.

PMID- 30208365
TI  - BASHH Doctors in Training.

PMID- 30208366
TI  - HIV care for Latin American patients in London: recognising the diversity and
      complex needs of this minority ethnic group: a service evaluation.

PMID- 30208367
TI  - Chlamydia retest: how should we remind you?

PMID- 30208368
TI  - Linkage to care after routine HIV, hepatitis B & C testing in the emergency
      department: the 'Going Viral' campaign.

PMID- 30208369
TI  - Clinical round-up.

PMID- 30208370
TI  - Adolescent inhalant abuse results in adrenal dysfunction and a hypermetabolic
      phenotype with persistent growth impairments.
AB  - : <br>Background/aims: Abuse of toluene products (e.g. glue-sniffing) primarily
      occurs during adolescence and has been associated with appetite suppression and
      weight impairments. However, the metabolic phenotype arising from adolescent
      inhalant abuse has never been fully characterised, and its persistence during
      abstinence and underlying mechanisms remain unknown. METHODS: Adolescent male
      Wistar rats (PND 27) were exposed to inhaled toluene (10,000ppm) (n=32) or air
      (n=48) for 1 hour/day, 3 days/week for 4 weeks, followed by 4 weeks abstinence.
      Twenty air-rats were pair-fed to the toluene group, to differentiate the direct
      effects of toluene from under-nutrition. Food intake, weight and growth were
      monitored. Metabolic hormones were measured after exposure and abstinence
      periods. Energy expenditure was measured using indirect calorimetry. Adrenal
      function was assessed using adrenal histology and hormone testing. RESULTS:
      Inhalant abuse suppressed appetite and increased energy expenditure. Reduced
      weight gain and growth were observed in both toluene and pair-fed groups.
      Compared to the pair-fed group, and despite normalisation of food intake, the
      suppression of weight and growth for toluene-exposed rats persisted during
      abstinence. After exposure, toluene rats had low fasting blood glucose and
      insulin compared to air and pair-fed groups. Consistent with adrenal
      insufficiency, adrenal hypertrophy and increased basal adrenocorticotropic
      hormone was observed in toluene-exposed rats, despite normal basal corticosterone
      levels. CONCLUSIONS: Inhalant abuse results in negative energy balance,
      persistent growth impairment, and endocrine changes suggestive of adrenal
      insufficiency. We conclude that adrenal insufficiency contributes to the negative
      energy balance phenotype, potentially presenting a significant additional health
      risk for inhalant users. <br>.

PMID- 30208372
TI  - Targeting Withdrawal Symptoms in Men Addicted to Methamphetamine With
      Transcranial Magnetic Stimulation: A Randomized Clinical Trial.

PMID- 30208371
TI  - Anti-Tumor Effects of Paeoniflorin on Epithelial-To-Mesenchymal Transition in
      Human Colorectal Cancer Cells.
AB  - BACKGROUND Colorectal cancer is one of the leading causes of death in China, and
      the development of effective drugs is urgently needed. Here, we report on
      Paeoniflorin (PF), a product isolated from the roots of the peony plant, as a
      possible candidate because of its anti-tumor effects on epithelial-to-mesenchymal
      transition (EMT) of PF in human colorectal cancer (CRC). MATERIAL AND METHODS
      Cell proliferation, wound healing, and Transwell assays were used to analyze the
      effects of PF on in vitro cell migration and invasion of HCT116 and SW480, 2
      colorectal cancer cell lines. The tumor xenograft model was used to verify the
      anti-metastasis effects of PF in vivo. The RNA and protein levels of epithelia
      cadherin (E-cadherin), Vimentin, and histone deacetylase2 (HDAC2) were measured
      by qPCR and Western blot analysis to explore the mechanism involved. RESULTS Our
      results showed that PF inhibited colorectal cancer cell migration and invasion
      and suppressed the metastatic potential of the cancer cells in vivo. Moreover, PF
      significantly decreased the expression of HDAC2 and Vimentin, while increasing
      the expression of E-cadherin. CONCLUSIONS These results suggest that PF inhibits
      colorectal cancer cell migration and invasion ability and reverses the EMT
      process, through inhibiting the expression of HDAC2, and then affects the
      expression level of E-cadherin and Vimentin at the cell level. Our results were
      also verified in the tumor xenograft model. This indicates that PF may be a
      candidate for colorectal cancer treatment.

PMID- 30208373
TI  - Association of Depression With Risk of Incident Systemic Lupus Erythematosus in
      Women Assessed Across 2 Decades.
AB  - Importance: It has long been hypothesized that depression may increase the risk
      of developing autoimmune disease; however, rigorous empirical evidence is sparse.
      Objective: To evaluate whether an association exists between depression and risk
      of incident systemic lupus erythematosus (SLE), a paradigmatic, systemic
      autoimmune disease. Design, Setting, and Participants: This 20-year prospective,
      longitudinal cohort study evaluated data collected from 2 cohorts of women
      participating in the Nurses' Health Study (1996-2012) and the Nurses' Health
      Study II (1993-2013). Data analyses were conducted from August 2017 to May 2018.
      Main Outcomes and Measures: Incident SLE with 4 or more American College of
      Rheumatology criteria was ascertained by self-report and confirmed by medical
      record review. Depression was assessed repeatedly throughout follow-up according
      to whether women reported having received a clinician's diagnosis of depression,
      regular antidepressant use, or a score of less than 60 on the 5-item Mental
      Health Inventory (MHI-5). Whether longitudinally assessed health risk factors
      (eg, cigarette smoking, body mass index, oral contraceptive use, menopause or
      postmenopausal hormone use, alcohol use, exercise, or diet) accounted for
      increased SLE risk among women with vs without depression was examined. Cox
      proportional hazards regression models were used to estimate risk of SLE. In
      addition, the association of depression lagged by 4 years, and depression status
      at baseline with incident SLE throughout follow-up was assessed. Results: Data
      from 194 483 women (28-93 years of age; 93% white) were included. During 20 years
      of follow-up, 145 cases of SLE occurred. Compared with women with no depression,
      women with a history of depression had a subsequent increased risk of SLE (HR,
      2.67; 95% CI, 1.91-3.75; P < .001). Adjustment for body mass index, cigarette
      smoking, and oral contraception and postmenopausal hormone use slightly
      attenuated associations (adjusted HR, 2.45; 95% CI, 1.74-3.45; P < .001). The SLE
      risk was elevated with each of the 3 following depression indicators modeled
      separately: clinician's diagnosis of depression (HR, 2.19; 95% CI, 1.29-3.71),
      antidepressant use (HR, 2.80; 95% CI, 1.94-4.05), and MHI-5 scores indicating
      depressed mood (HR, 1.70; 95% CI, 1.18-2.44). Associations remained strong when
      depression status was lagged by 4 years with respect to the outcome (HR, 1.99;
      95% CI, 1.32-3.00) and when depression status at baseline was used as the
      exposure (HR, 2.28; 95% CI, 1.54-3.37). Conclusions and Relevance: This study
      contributes to increasing evidence that depression may be associated with
      increased risk of SLE and suggests that the association is not fully explained by
      measured health factors or behaviors.

PMID- 30208374
TI  - Neurothekeomas: Multiple Symmetric Tumors in Both Hands.

PMID- 30208375
TI  - Urbanicity and Psychosis.

PMID- 30208376
TI  - Urbanicity and Psychosis-Reply.

PMID- 30208378
TI  - Unique Gadolinium Enhancement Pattern in Spinal Dural Arteriovenous Fistulas.
AB  - Importance: Spinal dural arteriovenous fistula (sDAVF) is often misdiagnosed as
      an inflammatory or a neoplastic myelopathy, often because of intraparenchymal
      gadolinium enhancement on magnetic resonance imaging (MRI); proper early
      diagnosis is important because deficits are reversible and a delay in treatment
      is associated with permanent morbidity. Tortuous flow voids on MRI are not
      universally present; thus, recognition of a unique gadolinium enhancement pattern
      may also aid in the early recognition and treatment of sDAVF. Objective: To
      describe a unique pattern of spinal cord gadolinium enhancement on MRI in sDAVF.
      Design, Setting, and Participants: This retrospective evaluation included
      pretreatment MRIs from 80 patients referred to the Mayo Clinic, Rochester,
      Minnesota, from January 1, 1997, through December 31, 2017, with a confirmed
      diagnosis of sDAVF and a control group of 144 patients with alternative confirmed
      myelopathy diagnoses. All participants underwent a neurologic evaluation at the
      Mayo Clinic. Main Outcomes and Measures: Evidence of at least 1 focal geographic
      nonenhancing area within a long segment of intense holocord gadolinium
      enhancement (termed the missing-piece sign) on MRI. Results: Of 51 patients with
      an sDAVF and a pretreatment MRI with gadolinium enhancement, 44 (86%) had
      intraparenchymal contrast enhancement, and 19 of these patients (43%) displayed
      the characteristic missing-piece sign. Of these 19 patients, symptom onset
      occurred at a median age of 67 years (range, 27-80 years); 15 patients were men.
      Progressive myelopathy features affecting the lower extremities occurred during a
      median of 33 months (range, 1-84 months). Eleven patients (58%) received an
      alternative diagnosis before confirmation of sDAVF. Tortuous flow voids were
      present on T2-weighted MRI in 13 of 19 patients. More than 1 digital subtraction
      angiogram was required for 5 patients to confirm the diagnosis. The missing-piece
      sign was not seen in any patients from the control group. Conclusions and
      Relevance: This unique gadolinium enhancement pattern in sDAVF was not found in a
      large control group of patients with other myelopathy. Identifying the missing
      piece sign on MRI could potentially result in earlier time to angiography with
      improved outcomes for patients with an sDAVF.

PMID- 30208377
TI  - The Latent Structure of Negative Symptoms in Schizophrenia.
AB  - Importance: Negative symptoms are associated with a range of poor clinical
      outcomes, and currently available treatments generally do not produce a
      clinically meaningful response. Limited treatment progress may be owing in part
      to poor clarity regarding latent structure. Prior studies have inferred latent
      structure using exploratory factor analysis, which has led to the conclusion that
      there are 2 dimensions reflecting motivation and pleasure (MAP) and diminished
      expressivity (EXP) factors. However, whether these conclusions are statistically
      justified remains unclear because exploratory factor analysis does not test
      latent structure. Confirmatory factor analysis (CFA) is needed to test competing
      models regarding the latent structure of a construct. Objective: To evaluate the
      fit of 4 models of the latent structure of negative symptoms in schizophrenia
      using CFA. Design, Setting, and Participants: Three cross-sectional studies were
      conducted on outpatients with schizophrenia who were rated on the 3 most
      conceptually contemporary measures: Scale for the Assessment of Negative Symptoms
      (SANS), Brief Negative Symptom Scale (BNSS), and Clinical Assessment Interview
      for Negative Symptoms (CAINS). Confirmatory factor analysis evaluated the
      following 4 models: (1) a 1-factor model; (2) a 2-factor model with EXP and MAP
      factors; (3) a 5-factor model with separate factors for the 5 domains of the
      National Institute of Mental Health consensus development conference (blunted
      affect, alogia, anhedonia, avolition, and asociality); and (4) a hierarchical
      model with 2 second-order factors reflecting EXP and MAP and 5 first-order
      factors reflecting the 5 consensus domains. Main Outcomes and Measures: Outcomes
      included CFA model fit statistics derived from symptom severity scores on the
      SANS, BNSS, and CAINS. Results: The study population included 860 outpatients
      with schizophrenia (68.0% male; mean [SD] age, 43.0 [11.4] years). Confirmatory
      factor analysis was conducted on each scale, including 268 patients for the SANS,
      192 for the BNSS, and 400 for the CAINS. The 1- and 2-factor models provided poor
      fit for the SANS, BNSS, and CAINS as indicated by comparative fit indexes (CFIs)
      and Tucker Lewis indexes (TLIs) less than 0.950, RMSEAs that exceeded the 0.080
      threshold, and WRMRs greater than 1.00. The 5-factor and hierarchical models
      provided excellent fit, with the 5-factor model being more parsimonious. The CFIs
      and TLIs met the 0.95 threshold and the 1.00 threshold for both factor models
      with all 3 measures. Interestingly, the RMSEAs for the 5-factor model and the
      hierarchical model fell under the 0.08 threshold for the BNSS and the CAINS but
      not the SANS. Conclusions and Relevance: These findings suggest that the recent
      trend toward conceptualizing the latent structure of negative symptoms as 2
      distinct dimensions does not adequately capture the complexity of the construct.
      The latent structure of negative symptoms is best conceptualized in relation to
      the 5 consensus domains. Implications for identifying pathophysiological
      mechanisms and targeted treatments are discussed.

PMID- 30208379
TI  - Development of a New Classification System for Idiopathic Inflammatory Myopathies
      Based on Clinical Manifestations and Myositis-Specific Autoantibodies.
AB  - Importance: Idiopathic inflammatory myopathies are heterogeneous in their
      pathophysiologic features and prognosis. The emergence of myositis-specific
      autoantibodies suggests that subgroups of patients exist. Objective: To develop a
      new classification scheme for idiopathic inflammatory myopathies based on
      phenotypic, biological, and immunologic criteria. Design, Setting, and
      Participants: An observational, retrospective cohort study was performed using a
      database of the French myositis network. Patients identified from referral
      centers for neuromuscular diseases were included from January 1, 2003, to
      February 1, 2016. Of 445 initial patients, 185 patients were excluded and 260
      adult patients with myositis who had complete data and defined historical
      classifications for polymyositis, dermatomyositis, and inclusion body myositis
      were enrolled. All patients were tested for anti-histidyl-ARN-t- synthetase
      (Jo1), anti-threonine-ARN-t-synthetase (PL7), anti-alanine-ARN-t-synthetase
      (PL12), anti-complex nucleosome remodeling histone deacetylase (Mi2), anti-Ku,
      anti-polymyositis/systemic scleroderma (PMScl), anti-topoisomerase 1 (Scl70), and
      anti-signal recognition particle (SRP) antibodies. A total of 708 variables were
      collected per patient (eg, cancer, lung involvement, and myositis-specific
      antibodies). Main Outcomes and Measures: Unsupervised multiple correspondence
      analysis and hierarchical clustering analysis to aggregate patients in subgroups.
      Results: Among 260 participants (163 [62.7%] women; mean age, 59.7 years; median
      age [range], 61.5 years [48-71 years]), 4 clusters of patients emerged. Cluster 1
      (n = 77) included patients who were male, white, and older than 60 years and had
      finger flexor and quadriceps weakness and findings of vacuolated fibers and
      mitochondrial abnormalities. Cluster 1 regrouped patients who had inclusion body
      myositis (72 of 77 patients [93.5%]; 95% CI, 85.5%-97.8%; P < .001). Cluster 2 (n
      = 91) regrouped patients who were women and had high creatine phosphokinase
      levels, necrosis without inflammation, and anti-SRP or anti-3-hydroxy-3
      methylglutaryl-coenzyme A reductase (HMGCR) antibodies corresponding to immune
      mediated necrotizing myopathy (53 of 91 [58.2%]; 95% CI, 47.4%-68.5%; P < .001).
      Cluster 3 (n = 52) regrouped patients who had dermatomyositis rash and anti-Mi2,
      anti-melanoma differentiation-associated protein 5 (MDA5), or anti-transcription
      intermediary factor-1gamma (TIF1gamma) antibodies, mainly corresponding with
      patients who had dermatomyositis (43 of 52 [82.7%]; 95% CI, 69.7%-91.8%; P <
      .001). Cluster 4 (n = 40) was defined by the presence of anti-Jo1 or anti-PL7
      antibodies corresponding to antisynthetase syndrome (36 of 40 [90.0%]; 95% CI,
      76.3%-97.2%; P < .001). The classification of an independent cohort (n = 50)
      confirmed the 4 clusters (Cohen kappa light, 0.8; 95% CI, 0.6-0.9). Conclusions
      and Relevance: These findings suggest a classification of idiopathic inflammatory
      myopathies with 4 subgroups: dermatomyositis, inclusion body myositis, immune
      mediated necrotizing myopathy, and antisynthetase syndrome. This classification
      system suggests that a targeted clinical-serologic approach for identifying
      idiopathic inflammatory myopathies may be warranted.

PMID- 30208380
TI  - Preventing Cognitive Decline in Black Individuals With Mild Cognitive Impairment:
      A Randomized Clinical Trial.
AB  - Importance: Mild cognitive impairment (MCI) is a transition state between normal
      cognitive aging and dementia that increases the risk for progressive cognitive
      decline. Preventing cognitive decline is a public health priority. Objective: To
      determine whether behavioral activation prevents cognitive and functional decline
      over 2 years in black individuals with MCI. Design, Setting, and Participants:
      Single-center, single-masked, attention-controlled randomized clinical trial.
      Participants were enrolled from June 21, 2011, to October 3, 2014, and follow-up
      ended December 13, 2016. Community-based recruitment and treatment of black
      individuals older than 65 years with amnestic MCI. Volunteer sample of 1390
      persons with memory complaints were screened. Overall, 536 individuals had
      baseline assessment, and 315 (58.8%) were ineligible, most often owing to normal
      cognition (205 of 315 [65%]) or dementia (59 of 315 [18.7%]); 221 fully eligible
      participants were randomized. Analyses were intention to treat. Interventions:
      Participants were randomized to behavioral activation, which aimed to increase
      cognitive, physical, and social activity (111 [50.2%]), or supportive therapy, an
      attention control treatment (110 [49.8%]). Main Outcomes and Measures: The
      prespecified primary outcome was a decline of 6 or more recalled words on the
      total recall score of the Hopkins Verbal Learning Test-Revised assessed at 6, 12,
      18, and 24 months. The secondary outcome was functional decline. Results: Of 221
      randomized participants (mean [SD] age, 75.8 [7.0] years, 175 women [79%]), 77
      behavioral activation participants (69.4%) and 87 supportive therapy participants
      (79.1%) had 2-year outcome assessments. After baseline, behavioral activation
      participants engaged in significantly more cognitive activities than supportive
      therapy participants. The 2-year incidence of memory decline was 1.2% (95% CI,
      0.2-6.4) for behavioral activation vs 9.3% (95% CI, 5.30-16.4) for supportive
      therapy (relative risk, 0.12; 95% CI, 0.02-0.74; P = .02). Behavioral activation
      was associated with stable everyday function, whereas supportive therapy was
      associated with decline (difference in slopes, 2.71; 95% CI, 0.12-5.30; P = .04).
      Rates of serious adverse events for behavioral activation and supportive therapy,
      respectively, were: falls (14 [13%] vs 28 [25%]), emergency department visits (24
      [22%] vs 24 [22%]), hospitalizations (36 [32%] vs 31 [28%]), and deaths (7 [5%]
      vs 3 [4%]). Conclusions and Relevance: Behavioral activation prevented cognitive
      and functional decline, but this finding requires further investigation. Black
      individuals have almost twice the rate of dementia as white individuals;
      behavioral activation may reduce this health disparity. Trial Registration:
      ClinicalTrials.gov Identifier: NCT01299766.

PMID- 30208381
TI  - Biliary-Enteric Drainage vs Primary Liver Transplant as Initial Treatment for
      Children With Biliary Atresia.
AB  - Importance: Some infants with biliary atresia are treated with primary liver
      transplant (pLT), but most are initially treated with biliary-enteric drainage
      (BED) with a subsequent salvage liver transplant. Given the improvements in liver
      transplant outcomes, it is important to determine whether BED treatment remains
      the optimal surgical algorithm for patients with biliary atresia. Objective: To
      compare the survival of patients with biliary atresia initially treated with BED
      with patients who underwent pLT. Design, Setting, and Participants: This cohort
      study used deidentified records from the California Office of Statewide Health
      Planning and Development database to identify patients with biliary atresia (n =
      1252) between January 1, 1990, through December 31, 2015. Patients were
      categorized into 1 of 2 cohorts: those who received BED treatment and those who
      underwent pLT. Excluded from the study were those born before January 1, 1995,
      and those without any documented operative intervention by age 5 years. Data
      analysis was performed from January 1, 1990, to December 31, 2015. Main Outcomes
      and Measures: Overall survival was compared between the BED and pLT cohorts using
      the Kaplan-Meier method. The treatment's association with treatment era was
      examined by comparing survival before 2002 and on or after January 1, 2002.
      Results: In total, 1252 patients with biliary atresia were identified. After
      exclusions, 626 remained; of these patients, 351 (56.1%) were female and 275
      (43.9%) were male with a median (interquartile range) age at intervention for
      initial BED treatment of 65 (48-81) days. Among the 626 patients studied, initial
      BED treatment was performed in 313 patients (50.0%), and pLT was performed in 313
      patients (50.0%). Although patients who underwent pLT had a higher mortality rate
      within the first 3 months after the procedure, they had a reduced risk of long
      term mortality compared with patients initially managed with BED treatment
      (hazard ratio [HR] >=6 months after the initial procedure, 0.19; 95% CI, 0.08
      0.42; P = .01). Patients requiring salvage liver transplant had a substantially
      higher risk of mortality than patients who received pLT (HR, 0.43; 95% CI 0.25
      0.76; P = .003). Those who underwent pLT had superior survival compared with BED
      treatment recipients on or after 2002 (HR, 0.16; 95% CI, 0.05-0.54; P < .001),
      and that persisted when censoring patients who underwent salvage liver transplant
      (HR, 0.23; 95% CI, 0.07-0.82; P = .01). Conclusions and Relevance: Patients who
      underwent pLT experienced superior long-term survival compared with patients who
      underwent BED treatment. Multi-institutional trials are needed to determine which
      initial treatment is most advantageous to patients with biliary atresia.

PMID- 30208382
TI  - Analysis of Work Requirement Exemptions and Medicaid Spending.

PMID- 30208383
TI  - Eosinopenia and Adverse Outcomes After Clostridium Difficile Infections: Of Mice
      and Men.

PMID- 30208384
TI  - Factors Associated With Long-term Benzodiazepine Use Among Older Adults.

PMID- 30208385
TI  - Medicaid Work Requirements-English Poor Law Revisited.

PMID- 30208386
TI  - Development and Validation of a Prediction Model for Mortality and Adverse
      Outcomes Among Patients With Peripheral Eosinopenia on Admission for Clostridium
      difficile Infection.
AB  - Importance: Recent evidence from an animal model suggests that peripheral loss of
      eosinophils in Clostridium difficile infection (CDI) is associated with severe
      disease. The ability to identify high-risk patients with CDI as early as the time
      of admission could improve outcomes by guiding management decisions. Objective:
      To construct a model using clinical indices readily available at the time of
      hospital admission, including peripheral eosinophil counts, to predict inpatient
      mortality in patients with CDI. Design, Setting, and Participants: In a cohort
      study, a total of 2065 patients admitted for CDI through the emergency department
      of 2 tertiary referral centers from January 1, 2005, to December 31, 2015, formed
      a training and a validation cohort. The sample was stratified by admission
      eosinophil count (0.0 cells/MUL or >0.0 cells/MUL), and multivariable logistic
      regression was used to construct a predictive model for inpatient mortality as
      well as other disease-related outcomes. Main Outcomes and Measures: Inpatient
      mortality was the primary outcome. Secondary outcomes included the need for a
      monitored care setting, need for vasopressors, and rates of inpatient colectomy.
      Results: Of the 2065 patients in the study, 1092 (52.9%) were women and patients
      had a mean (SD) age of 63.4 (18.4) years. Those with an undetectable eosinophil
      count at admission had increased in-hospital mortality in both the training (odds
      ratio [OR], 2.01; 95% CI, 1.08-3.73; P = .03) and validation (OR, 2.26; 95% CI,
      1.33-3.83; P = .002) cohorts in both univariable and multivariable analysis.
      Undetectable eosinophil counts were also associated with indicators of severe
      sepsis, such as admission to monitored care settings (OR, 1.40; 95% CI, 1.06
      1.86), the need for vasopressors (OR, 2.08; 95% CI, 1.32-3.28), and emergency
      total colectomy (OR, 2.56; 95% CI, 1.12-5.87). Other significant predictors of
      mortality at admission included increasing comorbidity burden (for each 1-unit
      increase: OR, 1.13; 95% CI, 1.05-1.22) and lower systolic blood pressures (for
      each 1-mm Hg increase: OR, 0.99; 95% CI, 0.98-1.00). In a subgroup analysis of
      patients presenting without initial tachycardia or hypotension, only patients
      with undetectable admission eosinophil counts, but not those with an elevated
      white blood cell count, had significantly increased odds of inpatient mortality
      (OR, 5.76; 95% CI, 1.99-16.64). Conclusions and Relevance: This study describes a
      simple, widely available, inexpensive model predicting CDI severity and mortality
      to identify at-risk patients at the time of admission.

PMID- 30208387
TI  - BRAF V600E Mutation as a Negative Prognostic Determinant in Resected Colorectal
      Liver Metastases-Reply.

PMID- 30208388
TI  - BRAF V600E Mutation as a Negative Prognostic Determinant in Resected Colorectal
      Liver Metastases.

PMID- 30208390
TI  - Patient With Unexplained Weight Loss, Anorexia, and Back Pain.

PMID- 30208391
TI  - A 71-Year-Old Man With Inferior ST-Segment Elevation.

PMID- 30208389
TI  - Postmortem Incidence of Acute Surgical- and Trauma-Associated Pathologic
      Conditons in Prison Inmates in Miami Dade County, Florida.

PMID- 30208392
TI  - Genetics, Biochemistry, and "Simple" Organisms Converge to Unlock Secrets in
      Histone Biology: The 2018 Albert Lasker Basic Medical Research Award.

PMID- 30208393
TI  - The Impact of Exposure With No Training: Implications for Future Partner Training
      Research.
AB  - Purpose: This research note reports on an unexpected negative finding related to
      behavior change in a controlled trial designed to test whether partner training
      improves the conversational skills of volunteers. Method: The clinical trial
      involving training in "Supported Conversation for Adults with Aphasia" utilized a
      single-blind, randomized, controlled, pre-post design. Eighty participants making
      up 40 dyads of a volunteer conversation partner and an adult with aphasia were
      randomly allocated to either an experimental or control group of 20 dyads each.
      Descriptive statistics including exact 95% confidence intervals were calculated
      for the percentage of control group participants who got worse after exposure to
      individuals with aphasia. Results: Positive outcomes of training in Supported
      Conversation for Adults with Aphasia for both the trained volunteers and their
      partners with aphasia were reported by Kagan, Black, Felson Duchan, Simmons
      Mackie, and Square in 2001. However, post hoc data analysis revealed that almost
      one third of untrained control participants had a negative outcome rather than
      the anticipated neutral or slightly positive outcome. Conclusions: If the results
      of this small study are in any way representative of what happens in real life,
      communication partner training in aphasia becomes even more important than
      indicated from the positive results of training studies. That is, it is possible
      that mere exposure to a communication disability such as aphasia could have
      negative impacts on communication and social interaction. This may be akin to
      what is known as a "nocebo" effect-something for partner training studies in
      aphasia to take into account.

PMID- 30208394
TI  - Effect of Portable Air Filtration Systems on Personal Exposure to Fine
      Particulate Matter and Blood Pressure Among Residents in a Low-Income Senior
      Facility: A Randomized Clinical Trial.
AB  - Importance: Fine particulate matter (smaller than 2.5 MUm) (PM2.5) air pollution
      is a major global risk factor for cardiovascular (CV) morbidity and mortality.
      Few studies have tested the benefits of portable air filtration systems in urban
      settings in the United States. Objective: To investigate the effectiveness of air
      filtration at reducing personal exposures to PM2.5 and mitigating related CV
      health effects among older adults in a typical US urban location. Design,
      Setting, and Participants: This randomized, double-blind crossover intervention
      study was conducted from October 21, 2014, through November 4, 2016, in a low
      income senior residential building in Detroit, Michigan. Forty nonsmoking older
      adults were enrolled, with daily CV health outcome and PM2.5 exposure
      measurements. Interventions: Participants were exposed to the following three 3
      day scenarios separated by 1-week washout periods: unfiltered air (sham
      filtration), low-efficiency (LE) high-efficiency particulate arrestance (HEPA)
      type filtered air, and high-efficiency (HE) true-HEPA filtered air using
      filtration systems in their bedroom and living room. Main Outcomes and Measures:
      The primary outcome was brachial blood pressure (BP). Secondary outcomes included
      aortic hemodynamics, pulse-wave velocity, and heart rate variability. Exposures
      to PM2.5 were measured in the participants' residences and by personal
      monitoring. Results: The 40 participants had a mean (SD) age of 67 (8) years (62%
      men). Personal PM2.5 exposures were significantly reduced by air filtration from
      a mean (SD) of 15.5 (10.9) MUg/m3 with sham filtration to 10.9 (7.4) MUg/m3 with
      LE fitration and 7.4 (3.3) MUg/m3 with HE filtration. Compared with sham
      filtration, any filtration for 3 days decreased brachial systolic and diastolic
      BP by 3.2 mm Hg (95% CI, -6.1 to -0.2 mm Hg) and 1.5 mm Hg (95% CI, -3.3 to 0.2
      mm Hg), respectively. A continuous decrease occurred in systolic and diastolic BP
      during the 3-day period of LE filtration, with a mean of 3.4 mm Hg (95% CI, -6.8
      to -0.1 mm Hg) and 2.2 mm Hg (95% CI, -4.2 to -0.3 mm Hg), respectively. For HE
      filtration, systolic and diastolic BP decreased by 2.9 mm Hg (95% CI, -6.2 to 0.5
      mm Hg) and 0.8 mm Hg (95% CI, -2.8 to 1.2 mm Hg), respectively. Most secondary
      outcomes were not significantly improved. Conclusions and Relevance: Results of
      this study showed that short-term use of portable air filtration systems reduced
      personal PM2.5 exposures and systolic BP among older adults living in a typical
      US urban location. The use of these relatively inexpensive systems is potentially
      cardioprotective against PM2.5 exposures and warrants further research. Trial
      Registration: ClinicalTrials.gov identifier: NCT03334565.

PMID- 30208395
TI  - Inappropriate Behavior by Patients and Their Families-Call It Out.

PMID- 30208397
TI  - I Have Insomnia-What Should I Do?

PMID- 30208396
TI  - Effectiveness of a Therapeutic Tai Ji Quan Intervention vs a Multimodal Exercise
      Intervention to Prevent Falls Among Older Adults at High Risk of Falling: A
      Randomized Clinical Trial.
AB  - Importance: Falls in older adults are a serious public health problem associated
      with irreversible health consequences and responsible for a substantial economic
      burden on health care systems. However, identifying optimal choices from among
      evidence-based fall prevention interventions is challenging as few comparative
      data for effectiveness are available. Objective: To determine the effectiveness
      of a therapeutically tailored tai ji quan intervention, Tai Ji Quan: Moving for
      Better Balance (TJQMBB), developed on the classic concept of tai ji (also known
      as tai chi), and a multimodal exercise (MME) program relative to stretching
      exercise in reducing falls among older adults at high risk of falling. Design,
      Setting, and Participants: A single-blind, 3-arm, parallel design, randomized
      clinical trial (February 20, 2015, to January 30, 2018), in 7 urban and suburban
      cities in Oregon. From 1147 community-dwelling adults 70 years or older screened
      for eligibility, 670 who had fallen in the preceding year or had impaired
      mobility consented and were enrolled. All analyses used intention-to-treat
      assignment. Interventions: One of 3 exercise interventions: two 60-minute classes
      weekly for 24 weeks of TJQMBB, entailing modified forms and therapeutic movement
      exercises; MME, integrating balance, aerobics, strength, and flexibility
      activities; or stretching exercises. Main Outcomes and Measures: The primary
      measure at 6 months was incidence of falls. Results: Among 670 participants
      randomized, mean (SD) age was 77.7 (5.6) years, 436 (65%) were women, 617 (92.1%)
      were white, 31 (4.6%) were African American. During the trial, there were 152
      falls (85 individuals) in the TJQMBB group, 218 (112 individuals) in the MME
      group, and 363 (127 individuals) in the stretching exercise group. At 6 months,
      the incidence rate ratio (IRR) was significantly lower in the TJQMBB (IRR, 0.42;
      95% CI, 0.31-0.56; P < .001) and MME groups (IRR, 0.60; 95% CI, 0.45-0.80; P =
      .001) compared with the stretching group. Falls were reduced by 31% for the
      TJQMBB group compared with the MME group (IRR, 0.69; 95% CI, 0.52-0.94; P = .01).
      Conclusions and Relevance: Among community-dwelling older adults at high risk for
      falls, a therapeutically tailored tai ji quan balance training intervention was
      more effective than conventional exercise approaches for reducing the incidence
      of falls. Trial Registration: ClinicalTrials.gov identifier: NCT02287740.

PMID- 30208399
TI  - The Discovery and Development of Propofol Anesthesia: The 2018 Lasker-DeBakey
      Clinical Medical Research Award.

PMID- 30208400
TI  - Documented Pain Diagnoses in Adults Prescribed Opioids: Results From the National
      Ambulatory Medical Care Survey, 2006-2015.

PMID- 30208398
TI  - Patient-Reported Experiences of Dialysis Care Within a National Pay-for
      Performance System.
AB  - Importance: Medicare's End-Stage Renal Disease Quality Incentive Program
      incorporates measures of perceived value into reimbursement calculations. In
      2016, patient experience became a clinical measure in the Quality Incentive
      Program scoring system. Dialysis facility performance in patient experience
      measures has not been studied at the national level to date. Objective: To
      examine associations among dialysis facility performance with patient experience
      measures and patient, facility, and geographic characteristics. Design: In this
      cross-sectional analysis, patients from a national end-stage renal disease
      registry receiving in-center hemodialysis in the United States on December 31,
      2014, were linked with dialysis facility scores on the In-Center Hemodialysis
      Consumer Assessment of Healthcare Providers and Systems (ICH-CAHPS) survey. Of
      4977 US dialysis facilities, 2939 (59.1%) reported ICH-CAHPS scores from April 8,
      2015, through January 11, 2016. Multivariable linear regression models with
      geographic random effects were used to examine associations of facility ICH-CAHPS
      scores with patient, dialysis facility, and geographic characteristics and to
      identify the amount of total between-facility variation in patient experience
      scores explained by these categories. Data were analyzed from September 15, 2017,
      through June 1, 2018. Exposures: Dialysis facility, geographic characteristic,
      and 10% change in patient characteristics. Main Outcomes and Measures: Dialysis
      facility ICH-CAHPS scores and the total between-facility variation explained by
      different categories of characteristics. Results: Of the 2939 facilities included
      in the analysis, adjusted mean ICH-CAHPS scores were 2.6 percentage points (95%
      CI, 1.5-3.7) lower in for-profit facilities, 1.6 percentage points (95% CI, 0.9
      2.2) lower in facilities owned by large dialysis organizations, and 2.3
      percentage points (95% CI, 0.5-4.2) lower in free-standing facilities compared
      with their counterparts. More nurses per patient was associated with 0.2
      percentage points (95% CI, 0.03-0.3) higher scores; a privately insured patient
      population was associated with 1.2 percentage points (95% CI, 0.2-2.2) higher
      scores. Facilities with higher proportions of black patients had 0.95 percentage
      points (95% CI, 0.78-1.12) lower scores; more Native American patients, 1.00
      percentage point (95% CI, 0.39-1.60) lower facility scores. Geographic location
      and dialysis facility characteristics explained larger proportions of the overall
      between-facility variation in ICH-CAHPS scores than did patient characteristics.
      Conclusions and Relevance: This study suggests that for-profit operation, free
      standing status, and large dialysis organization designation were associated with
      less favorable patient-reported experiences of care. Patient experience scores
      varied geographically, and black and Native American populations reported less
      favorable experiences. The study findings suggest that perceived quality of care
      delivered in these settings are of concern, and that there may be opportunities
      for improved implementation of patient experience surveys as is highlighted.

PMID- 30208401
TI  - Inflammation, Superadded Inflammation, and Out-of-Proportion Inflammation in
      Atherosclerosis.

PMID- 30208402
TI  - A Student Reflection on Doctoring With Confidence: Mind the Gap.

PMID- 30208404
TI  - Annals Understanding Clinical Research: Interpreting Results With Large P Values.

PMID- 30208403
TI  - Reliability of Measures of N1 Peak Amplitude of the Compound Action Potential in
      Younger and Older Adults.
AB  - Purpose: Human auditory nerve (AN) activity estimated from the amplitude of the
      first prominent negative peak (N1) of the compound action potential (CAP) is
      typically quantified using either a peak-to-peak measurement or a baseline
      corrected measurement. However, the reliability of these 2 common measurement
      techniques has not been evaluated but is often assumed to be relatively poor,
      especially for older adults. To address this question, the current study (a)
      compared test-retest reliability of these 2 methods and (b) tested the extent to
      which measurement type affected the relationship between N1 amplitude and
      experimental factors related to the stimulus (higher and lower intensity levels)
      and participants (younger and older adults). Method: Click-evoked CAPs were
      recorded in 24 younger (aged 18-30 years) and 20 older (aged 55-85 years) adults
      with clinically normal audiograms up to 3000 Hz. N1 peak amplitudes were
      estimated from peak-to-peak measurements (from N1 to P1) and baseline-corrected
      measurements for 2 stimulus levels (80 and 110 dB pSPL). Baseline-corrected
      measurements were made with 4 baseline windows. Each stimulus level was presented
      twice, and test-retest reliability of these 2 measures was assessed using the
      intraclass correlation coefficient. Linear mixed models were used to evaluate the
      extent to which age group and click level uniquely predicted N1 amplitude and
      whether the predictive relationships differed between N1 measurement techniques.
      Results: Both peak-to-peak and baseline-corrected measurements of N1 amplitude
      were found to have good-to-excellent reliability, with intraclass correlation
      coefficient values > 0.60. As expected, N1 amplitudes were significantly larger
      for younger participants compared with older participants for both measurement
      types and were significantly larger in response to clicks presented at 110 dB
      pSPL than at 80 dB pSPL for both measurement types. Furthermore, the choice of
      baseline window had no significant effect on N1 amplitudes using the baseline
      corrected method. Conclusions: Our results suggest that measurements of AN
      activity can be robustly and reliably recorded in both younger and older adults
      using either peak-to-peak or baseline-corrected measurements of the N1 of the
      CAP. Peak-to-peak measurements yield larger N1 response amplitudes and are the
      default measurement type for many clinical systems, whereas baseline-corrected
      measurements are computationally simpler. Furthermore, the relationships between
      AN activity and stimulus- and participant-related variables were not affected by
      measurement technique, which suggests that these relationships can be compared
      across studies using different techniques for measuring the CAP N1.

PMID- 30208405
TI  - Chronic Pain Among Suicide Decedents, 2003 to 2014: Findings From the National
      Violent Death Reporting System.
AB  - Background: More than 25 million adults in the United States have chronic pain.
      Chronic pain has been associated with suicidality, but previous studies primarily
      examined nonfatal suicidal behaviors rather than suicide deaths associated with
      chronic pain or the characteristics of such deaths. Objective: To estimate the
      prevalence of chronic pain among suicide decedents in a large multistate sample
      and to characterize suicide decedents with and without chronic pain. Design:
      Retrospective analysis of National Violent Death Reporting System (NVDRS) data.
      The NVDRS links death certificate, coroner or medical examiner, and law
      enforcement data collected by investigators, who often interview informants who
      knew the decedent to gather information on precipitating circumstances
      surrounding the suicide. Information is abstracted by using standard coding
      guidance developed by the Centers for Disease Control and Prevention. Setting: 18
      states participating in the NVDRS. Participants: Suicide decedents with and
      without chronic pain who died during 1 January 2003 to 31 December 2014.
      Measurements: Demographic characteristics, mechanism of death, toxicology
      results, precipitating circumstances (mental health, substance use, interpersonal
      problems, life stressors), and suicide planning and intent. Results: Of 123 181
      suicide decedents included in the study, 10 789 (8.8%) had evidence of chronic
      pain, and the percentage increased from 7.4% in 2003 to 10.2% in 2014. More than
      half (53.6%) of suicide decedents with chronic pain died of firearm-related
      injuries and 16.2% by opioid overdose. Limitation: The results probably
      underrepresent the true percentage of suicide decedents who had chronic pain,
      given the nature of the data and how they were captured. Conclusion: Chronic pain
      may be an important contributor to suicide. Access to quality, comprehensive pain
      care and adherence to clinical guidelines may help improve pain management and
      patient safety. Primary Funding Source: None.

PMID- 30208406
TI  - Pain, Opioids, and Suicide Mortality in the United States.

PMID- 30208407
TI  - Association Between Aortic Vascular Inflammation and Coronary Artery Plaque
      Characteristics in Psoriasis.
AB  - Importance: Inflammation is critical to atherosclerosis. Psoriasis, a chronic
      inflammatory disease associated with early cardiovascular events and increased
      aortic vascular inflammation (VI), provides a model to study the process of early
      atherogenesis. Fludeoxyglucose F 18 positron emission tomography/computed
      tomography (18F-FDG PET/CT) helps quantify aortic VI, and coronary computed
      tomography angiography provides coronary artery disease (CAD) assessment through
      evaluation of total plaque burden (TB) and noncalcified coronary plaque burden
      (NCB), luminal stenosis, and high-risk plaques (HRP). To our knowledge,
      association between aortic VI and broad CAD indices has not yet been assessed in
      a chronic inflammatory disease state. Such a study may provide information
      regarding the utility of aortic VI in capturing early CAD. Objective: To assess
      the association between aortic VI and CAD indices, including TB, NCB, luminal
      stenosis, and HRP prevalence, in psoriasis. Design, Setting, and Participants: In
      a cross-sectional cohort study at the National Institutes of Health, 215
      consecutive patients with psoriasis were recruited from surrounding outpatient
      dermatology practices. All patients underwent 18F-FDG PET/CT for aortic VI
      assessment, and 190 of 215 patients underwent coronary computed tomography
      angiography to characterize CAD. The study was conducted between January 1, 2013,
      and May 31, 2017. Data were analyzed in March 2018. Exposures: Aortic VI assessed
      by 18F-FDG PET/CT. Main Outcomes and Measures: Primary outcome: TB and NCB.
      Secondary outcomes: luminal stenosis and HRP. Results: Among 215 patients with
      psoriasis (mean [SD] age, 50.4 [12.6] years; 126 men [59%]), patients with
      increased aortic VI had increased TB (standardized beta = 0.48; P < .001), and
      higher prevalence of luminal stenosis (OR, 3.63; 95% CI, 1.71-7.70; P = .001) and
      HRP (OR, 3.05; 95% CI, 1.42-6.47; P = .004). The aortic VI and TB association was
      primarily driven by NCB (beta = 0.49; P < .001), whereas the aortic VI and HRP
      association was driven by low-attenuation plaque (OR, 5.63; 95% CI, 1.96-16.19; P
      = .001). All associations of aortic VI remained significant after adjustment for
      cardiovascular risk factors: aortic VI and TB (beta = 0.23; P < .001), NCB (beta
      = 0.24; P < .001), luminal stenosis (OR, 3.40; 95% CI, 1.40-8.24; P = .007), and
      HRP (OR, 2.72; 95% CI, 1.08-6.83; P = .03). No association was found between
      aortic VI and dense-calcified coronary plaque burden. Conclusions and Relevance:
      Aortic VI is associated with broad CAD indices, suggesting that aortic VI may be
      a surrogate for early CAD. Larger prospective studies need to assess these
      associations longitudinally and examine treatment effects on these outcomes.

PMID- 30208408
TI  - A Phonetic Complexity-Based Approach for Intelligibility and Articulatory
      Precision Testing: A Preliminary Study on Talkers With Amyotrophic Lateral
      Sclerosis.
AB  - Purpose: This study describes a phonetic complexity-based approach for speech
      intelligibility and articulatory precision testing using preliminary data from
      talkers with amyotrophic lateral sclerosis. Method: Eight talkers with
      amyotrophic lateral sclerosis and 8 healthy controls produced a list of 16 low
      and high complexity words. Sixty-four listeners judged the samples for
      intelligibility, and 2 trained listeners completed phoneme-level analysis to
      determine articulatory precision. To estimate percent intelligibility, listeners
      orthographically transcribed each word, and the transcriptions were scored as
      being either accurate or inaccurate. Percent articulatory precision was
      calculated based on the experienced listeners' judgments of phoneme distortions,
      deletions, additions, and/or substitutions for each word. Articulation errors
      were weighted based on the perceived impact on intelligibility to determine word
      level precision. Results: Between-groups differences in word intelligibility and
      articulatory precision were significant at lower levels of phonetic complexity as
      dysarthria severity increased. Specifically, more severely impaired talkers
      showed significant reductions in word intelligibility and precision at both
      complexity levels, whereas those with milder speech impairments displayed
      intelligibility reductions only for more complex words. Articulatory precision
      was less sensitive to mild dysarthria compared to speech intelligibility for the
      proposed complexity-based approach. Conclusions: Considering phonetic complexity
      for dysarthria tests could result in more sensitive assessments for detecting and
      monitoring dysarthria progression.

PMID- 30208409
TI  - State-Level Population Estimates of Individuals Subject to and Not Meeting
      Proposed Medicaid Work Requirements.

PMID- 30208413
TI  - Speed-Accuracy Trade-Offs and Adaptation Deficits in Aphasia: Finding the "Sweet
      Spot" Between Overly Cautious and Incautious Responding.
AB  - Purpose: After stroke, how well do people with aphasia (PWA) adapt to the altered
      functioning of their language system? When completing a language-dependent task,
      how well do PWA balance speed and accuracy when the goal is to respond both as
      quickly and accurately as possible? The current work investigates adaptation
      theory (Kolk & Heeschen, 1990) in the context of speed-accuracy trade-offs in a
      lexical decision task. PWA were predicted to set less beneficial speed-accuracy
      trade-offs than matched controls, and at least some PWA were predicted to present
      with adaptation deficits, with impaired accuracy or response times attributable
      to speed-accuracy trade-offs. Method: The study used the diffusion model
      (Ratcliff, 1978), a computational model of response time for simple 2-choice
      tasks. Parameters of the model can be used to distinguish basic processing
      efficiency from the overall level of caution in setting response thresholds and
      were used here to characterize speed-accuracy trade-offs in 20 PWA and matched
      controls during a lexical decision task. Results: Models showed that PWA and
      matched control groups did not differ overall in how they set response thresholds
      for speed-accuracy trade-offs. However, case series analyses showed that 40% of
      the PWA group displayed the predicted adaptation deficits, with impaired accuracy
      or response time performance directly attributable to overly cautious or overly
      incautious response thresholds. Conclusions: Maladaptive speed-accuracy trade
      offs appear to be present in some PWA during lexical decision, leading to
      adaptation deficits in performance. These adaptation deficits are potentially
      treatable, and clinical implications and next steps for translational research
      are discussed.

PMID- 30208410
TI  - An Acute Injury Model for the Phenotypic Characteristics of Geographic Atrophy.
AB  - Purpose: Geographic atrophy (GA) is the late stage of non-neovascular age-related
      macular degeneration. A lack of animal models for GA has hampered treatment
      efforts. Presented herein is a rat model for GA using subretinal injection of
      sodium iodate (NaIO3). Methods: Rats were given subretinal injections of NaIO3 (5
      MUg/MUL) using a pico-injector. Fundus photographs and spectral domain optical
      coherent tomography scans were collected at 1, 3, 7, 14, and 28 days after
      injection, at which time rats were euthanized and eyes were enucleated. Eyes were
      either cryopreserved or dissected into retinal and choroidal flatmounts.
      Fluorescence immunohistochemistry was performed for retinal glial fibrillary
      acidic protein (activated Muller cells and astrocytes) and vimentin (Muller
      cells), as well as peanut agglutin lectin (photoreceptors) labeling. RPE/choroids
      were labeled for RPE65 and CD34. Images were collected on Zeiss confocal
      microscopes. Results: Fundus photos, spectral domain optical coherent tomography,
      and RPE65 staining revealed well-demarcated areas with focal loss of RPE and
      photoreceptors in NaIO3-treated rats. At 1 day after injection, RPE cells
      appeared normal. By 3 days, there was patchy RPE and photoreceptor loss in the
      injected area. RPE and photoreceptors were completely degenerated in the injected
      area by 7 days. A large subretinal glial membrane occupied the degenerated area.
      Choriocapillaris was highly attenuated in the injected area at 14 and 28 days.
      Conclusions: The rat model reported herein mimics the photoreceptor cell loss,
      RPE atrophy, glial membrane formation, and choriocapillaris degeneration seen in
      GA. This model will be valuable for developing and testing drugs and progenitor
      cell regenerative therapies for GA.

PMID- 30208414
TI  - Evaluating Hearing Aid Management: Development of the Hearing Aid Skills and
      Knowledge Inventory (HASKI).
AB  - Purpose: Although hearing health care clinicians provide training on hearing aid
      handling and management as part of the rehabilitation program, clinical studies
      suggest that the level of management skill demonstrated by hearing aid owners is
      low. In the absence of a comprehensive clinical survey to identify these
      shortfalls in clinical training, the objective of this study was to develop and
      report the psychometric properties of the Hearing Aid Skills and Knowledge
      Inventory (HASKI: a self-administered version and a clinician-administered
      version). The HASKI evaluates the knowledge and skills required for hearing aid
      management. A secondary aim was to report the prevalence of hearing aid
      management difficulties in an Australian population. Method: The development of
      the HASKI and the investigation of its psychometric properties in a prospective
      convenience cohort of 518 adult hearing aid owners, ranging in age from 18 to 97
      years (M = 71 years, SD = 14), 60% male, 38% female, and 2% undisclosed,
      recruited from 7 hearing clinics across Australia, were used. Results: The HASKI
      (both the self-administered and clinician administered) demonstrated high
      internal consistency, interdimensional relationships, construct validity, test
      retest reliability, interobserver reliability, and criterion validity. A range of
      aptitudes were observed from low to full competency, with 99% of participants
      indicating difficulty with at least 1 item on the survey. Conclusions: The
      Hearing Aid Skills and Knowledge Inventories are valid and reliable measures of
      hearing aid handling and management skills with good potential for use in
      clinical settings. Hearing aid management is an area of difficulty for the
      majority of hearing aid owners, indicating the need for clinicians to improve the
      efficacy of hearing aid management training delivered.

PMID- 30208415
TI  - Acquisition and Generalization Responses in Aphasia Naming Treatment: A Meta
      Analysis of Semantic Feature Analysis Outcomes.
AB  - Purpose: This meta-analysis synthesizes results from published studies that used
      semantic feature analysis (SFA) treatment to improve naming for people with
      aphasia. It examines how both person- and treatment-related variables affected
      the likelihood of correct naming responses in individual probe sessions for both
      acquisition (treated) and generalization (untreated) stimuli. Method: The meta
      analysis compiled data from 12 studies analyzing a total of 35 participants with
      aphasia. It used mixed-effects models as a novel statistical tool to examine the
      effects of 2 sets of variables on naming performance: treatment-related
      variables, including treatment phase (baseline vs. treatment), dosage (number of
      treatment sessions), and stimulus type (treated vs. untreated, semantically
      related vs. unrelated items), and person-specific variables, including degree of
      language impairment and demographic variables (age, time poststroke). Results:
      Results of the meta-analysis revealed that SFA intervention promoted increased
      naming accuracy during naming probes when comparing baseline and treatment
      phases. In addition, increased dosages of SFA were associated with increased
      naming accuracy, and treatment-related gains were larger for acquisition
      (treated) than generalization (untreated) stimuli, likewise for related versus
      unrelated generalization stimuli. Furthermore, a subset of person-specific
      variables was predictive of SFA-related gains: Language impairment variables were
      related to treatment-related changes in naming performance, but demographic
      variables were not. Conclusion: These results provide group-level evidence for
      the efficacy of SFA as well as preliminary estimates of how much naming
      performance benefit is engendered by varying dosages of SFA. The results also
      provide promising and previously unobserved evidence of potential person-level
      predictors of SFA treatment response.

PMID- 30208417
TI  - IOP, IOP Transient Impulse, Ocular Perfusion Pressure, and Mean Arterial Pressure
      Relationships in Nonhuman Primates Instrumented With Telemetry.
AB  - Purpose: To characterize relationships between intraocular pressure (IOP), mean
      arterial pressure (MAP), ocular perfusion pressure (OPP), IOP transient impulse,
      and IOP baseline impulse using continuous telemetry in nonhuman primates.
      Methods: We used our validated implantable telemetry system to wirelessly record
      bilateral IOP and arterial BP at 500 Hz in 7 eyes of 4 male rhesus macaques, aged
      4 to 5 years. IOP, MAP, OPP, IOP transient impulse, and IOP baseline impulse were
      averaged into 1-hour periods over 20 days for each NHP. IOP transient impulse was
      defined as the portion of total IOP due to transient IOP fluctuations <0.5
      seconds duration alone and IOP baseline impulse as the remaining area under the
      IOP versus time curve. OPP was defined as arterial BP-IOP (calculated
      continuously), and MAP was the hourly average of the continuous BP curve.
      Relationships between the variables were analyzed for each 24-hour period using
      either multivariate linear regression or Spearman Correlation Coefficients as
      appropriate. Results: Over twenty 24-hour periods, IOP transient impulse and OPP
      showed significant positive relationship in all eyes, which was driven largely by
      the data during waking hours. There was no significant relationship between IOP
      and MAP, IOP transient impulse and MAP, or IOP baseline impulse and IOP transient
      impulse. Conclusions: There are significant positive relationships between the
      frequency and/or size of transient IOP fluctuations (IOP transient impulse) and
      OPP. A possible explanation of this finding is that higher OPP, as well as a
      greater number of blinks and saccades (the primary sources of IOP transients),
      are associated with increased activity.

PMID- 30208418
TI  - Visual Search in Amblyopia: Abnormal Fixational Eye Movements and Suboptimal
      Sampling Strategies.
AB  - Purpose: Microsaccades shift the image on the fovea and counteract visual fading.
      They are also thought to serve as an optimal sampling strategy while viewing
      complex visual scenes. The goal of our study was to assess visual search in
      amblyopic children. Methods: Twenty-one amblyopic children with varying severity
      of amblyopia and 10 healthy controls were recruited. Eye movements were recorded
      using infrared video-oculography during amblyopic and fellow eye viewing while
      the subjects performed (1) visual fixation, (2) exploration of a blank scene, and
      (3) visual search task (spot the difference between two images). The number of
      correctly identified picture differences and reaction time were recorded.
      Microsaccade, saccades, and intersaccadic drifts were analyzed in patients
      without latent nystagmus (LN). Slow phase velocities were computed for patients
      with LN. Results: Both patients with and without LN were able to spot the same
      number of differences but took longer during fellow eye viewing compared to
      controls. The ability to identify differences was diminished during amblyopic eye
      viewing particularly those with LN and severe amblyopia. We found reduced
      frequencies of microsaccades and saccades in both amblyopic and fellow eyes
      during fixation and visual search but not during exploration of blank scene.
      Across all tasks, amblyopes with LN had increased intersaccadic drifts.
      Conclusions: Our findings suggest that deficient microsaccade and saccadic
      activity contributes to poorer sampling strategy in amblyopia, which is seen in
      both amblyopic and fellow eye. These deficits are more notable among subjects who
      experienced binocular decorrelation earlier in life, with subsequent development
      of LN.

PMID- 30208416
TI  - A Potential Bias in Subjective Ratings of Mental Effort.
AB  - Purpose: Subjective reports of listening effort are frequently inconsistent with
      behavioral and physiological findings. A potential explanation is that
      participants unwittingly substitute an easier question when faced with a judgment
      that requires computationally expensive analysis (i.e., heuristic response
      strategies). The purpose of this study was to investigate whether participants
      substitute the question "How did I perform?" when asked "How much effort did that
      take?". Method: Participants completed 2 sets of online surveys containing a text
      based, multiple-choice synonym task. Expected performance and mental effort were
      manipulated across sets in 4 experiments, using a visual masking technique shown
      to correlate with speech-reception-testing in noise. Experiment 1 was designed to
      yield stable accuracy and differing effort across sets. Experiment 2 elicited
      differing accuracy and stable effort. Experiments 3 and 4 manipulated accuracy
      and performance in opposite directions. Participants included 273 adults (aged 19
      68 years, M = 38.4 years). Results: Experiment 1 revealed no influence of
      perceived performance on ratings of effort when accuracy was stable. Experiment 2
      showed that ratings of effort differed inversely with ratings of performance
      (lower performance and increased effort). Experiments 3 and 4 also demonstrated
      that participants rated effort in a manner inversely related to performance,
      regardless of the effort inherent in the condition. Conclusions: Participants
      likely substitute an easier question when asked to rate the multidimensional
      construct of mental effort. The results presented here suggest that perceived
      performance can serve as a ready heuristic and may explain the dissociation
      between subjective measures of listening effort and behavioral and physiological
      measures.

PMID- 30208420
TI  - Characteristics of the Corneal Endothelium Across the Primary Angle Closure
      Disease Spectrum.
AB  - Purpose: To evaluate the corneal endothelial characteristics across the primary
      angle closure (PAC) disease spectrum amongst patients diagnosed as PAC suspects
      (PACS), PAC, PAC glaucoma (PACG), and previous acute PAC (APAC). Methods: We
      analyzed a total of 529 subjects (51 PACS, 170 PAC, 234 PACG, and 74 with
      previous APAC). All subjects had undergone laser peripheral iridotomy prior to
      study recruitment. Corneal endothelial parameters were measured using a
      noncontact specular microscope and the following parameters were obtained: mean
      central endothelial cell density (ECD; cells/mm2), coefficient of variation (CV)
      in cell area, and percentage of hexagonal cells. Results: The mean age of the
      subjects was 65.1 +/- 8.2 years, and 55.2% were females. The mean central ECD was
      2582.0 +/- 472.8 cells/mm2 in PACS, 2566.0 +/- 408.3 cells/mm2 in PAC, 2523.8 +/-
      406.8 cells/mm2 in PACG, and 2504.0 +/- 558.1 cells/mm2 in APAC, with no
      significant differences in ECD across the subgroups (P = 0.61). The CV was lowest
      in PACS (34.38 +/- 6.05 MUm2/cell), and highest in APAC (37.61 +/- 7.98
      MUm2/cell), but the differences were not significant (P = 0.07). Likewise, the
      percentage of hexagonality was not significantly different between the groups. A
      subgroup analysis on the eyes with previous APAC with their fellow eye also
      showed no significant differences in the corneal endothelial characteristics.
      Conclusions: The corneal ECD and morphological characteristics such as CV and
      hexagonality are not significantly different across the PAC disease spectrum.
      This may reflect the lack of a sustained and/or dramatic IOP insult and/or an
      insignificant deleterious effect from medications, age, and chronicity on corneal
      endothelial parameters.

PMID- 30208421
TI  - Low-Level Nighttime Light Therapy for Age-Related Macular Degeneration: A
      Randomized Clinical Trial.
AB  - Purpose: To investigate the safety, acceptability, and effectiveness of light
      therapy on the progression of AMD over 12 months. Methods: This was a phase
      I/IIa, prospective, proof-of-concept, single-center, unmasked randomized
      controlled trial. Sixty participants (55 to 88 years) with early AMD in the study
      eye and neovascular AMD (nAMD) in the fellow eye were recruited from a hospital
      nAMD clinic. Eligible participants were randomized (ratio 1:1) to receive light
      therapy or to an untreated control group. Light therapy was delivered via a light
      emitting mask (peak 505 nm, 23 scotopic Td), which was worn each night for 12
      months. Co-primary outcome measures were disease progression (onset of nAMD or
      increased drusen volume beyond test-retest limits) and change in time constant of
      cone dark adaptation. Other main outcomes included adverse events, compliance,
      and subjective sleep quality data. Results: Disease progression over 12 months
      was seen in 38.1% (18.1%-61.6% confidence interval [CI]) of intervention
      participants and 48.3% (29.4%-67.5% CI) of controls (Mantel-Haenszel test, common
      odds ratio = 0.763, P = 0.495). A significantly larger delay in cone adaptation
      was observed in the intervention group (1.66 +/- 0.61 minutes) than in the
      control group (0.66 +/- 0.49 minutes) over the follow-up period. No reported
      adverse events were deemed to be associated with the intervention. Conclusions:
      Although acceptable to the patients, light therapy did not have a substantial
      effect on the progression of early AMD over 12 months. Further investigation is
      necessary to discover the permanency and cause of the adverse effect of light
      therapy on dark adaptation.

PMID- 30208419
TI  - Refraction and Change in Refraction Over a 20-Year Period in the Beaver Dam Eye
      Study.
AB  - Purpose: Hyperopic shifts in refraction have been consistently reported in adults
      over 40, followed by myopic shifts after age 70. Although potential factors
      underlying these changes in refraction in older adults have been investigated
      previously, the studies were restricted by the limited longitudinal data
      available. The authors of this study sought to better characterize the long-term
      trajectory of refraction in older adults using 20 years of prospective data.
      Methods: The impact of cohort effects on refraction over 20 years was examined.
      Generalized estimating equations were used to evaluate the etiologic factors
      underlying refraction and changes in refraction measured over a 20-year period
      (1988-2010) among adults over age 40 from the Beaver Dam Eye Study. Results: Only
      individuals with nuclear cataract experienced a myopic shift in refraction,
      showing a 0.25 diopter (D) decrease (95% confidence interval [CI]: -0.44 D to 
      0.07 D) over a five-year period. Individuals with mild and moderate nuclear
      sclerosis showed varying degrees of hyperopic shifts over five years (0.22 D: 95%
      CI: 0.20 D-0.25 D; 0.23 D: 95% CI: 0.20 D-0.27 D, respectively). Conclusions:
      Nuclear cataract is the primary contributor to the myopic shift among older
      individuals. Birth cohort effects on baseline refraction but not change in
      refraction were observed.

PMID- 30208422
TI  - Effect of Resveratrol on Sirtuins, OPA1, and Fis1 Expression in Adult Zebrafish
      Retina.
AB  - Purpose: We determined whether sirtuins (SIRT1-SIRT7) are expressed in the
      zebrafish retina, evaluated the modulatory effect of resveratrol in the normal
      retina, and examined N-Methyl-D-aspartic acid (NMDA)-induced zebrafish retinal
      damage associated with mitochondrial sirtuins and mitochondrial fusion and
      fission mediators, OPA1 and Fis1. Methods: Sirtuins, OPA1, and Fis1 mRNA
      expression was analyzed by RT-PCR and quantitative real time PCR (qPCR) in adult
      zebrafish (AB type) retina and liver. qPCR showed an effect of resveratrol on
      SIRTs (SIRT1, 3, 4, 5) and OPA1 and Fis1 in low and high concentrations (5 and 50
      mg/L) at different time points (0, 1, 24, and 48 hours) in the retina. Western
      blots were performed to examine the expression of SIRTs and OPA1 proteins under
      high concentrations of resveratrol for 24 hours. Hematoxylin and eosin staining,
      qPCR and mitochondrial copy number, and DNA damage assays then were used to
      confirm the protective effects of resveratrol on NMDA-induced retinal damage.
      Results: The seven sirtuins and OPA1 were highly expressed in zebrafish retina
      compared to the liver. Treatment with resveratrol promoted SIRT1, mitochondrial
      sirtuins, and OPA1 gene and protein expression, and improved mitochondrial DNA
      repair in adult zebrafish retina. Interestingly, the effect of resveratrol on
      SIRT4 gene and protein expression was significantly higher in the zebrafish
      retina. Importantly, resveratrol offered protection against NMDA-induced retinal
      damage by activating the SIRT1 gene and subsequent protein expression.
      Mitochondrial sirtuins and OPA1 genes likely had a role in regulating
      mitochondrial dynamics. Conclusions: To our knowledge, our study is the first
      composite analysis of sirtuins in adult zebrafish retina and provides sufficient
      evidence that resveratrol, as an activator of SIRT1, protects NMDA-induced
      zebrafish retinal damage by potentially mediating mitochondrial sirtuins and OPA1
      genes.

PMID- 30208424
TI  - Progression in X-linked Retinitis Pigmentosa Due to ORF15-RPGR Mutations:
      Assessment of Localized Vision Changes Over 2 Years.
AB  - Purpose: To determine the progression rate and the variability of rod and cone
      sensitivities in patients with X-linked retinitis pigmentosa (XLRP) caused by
      mutations in ORF15-RPGR. Methods: ORF15-RPGR-XLRP patients (n = 15) were studied
      prospectively over 2 years with static perimetry sampling the visual field under
      dark-adapted and light-adapted conditions on a 12 degrees  square grid covering
      168 degrees  width and 84 degrees  height. Natural history of rod and cone
      sensitivity loss and test-retest variability were estimated. Data were analyzed
      pointwise as well as averaged across small regions of neighboring loci of
      approximately 80 mm2 (900 deg2) in size representing the likely extent of
      localized gene therapy injections. Results: Retinal loci with mild to moderate
      loss of sensitivity tended to be in the mid- to far-peripheral retina in most
      patients. When averaged across small regions, dark-adapted rod vision progressed
      at an average of 2 dB per year with a coefficient of repeatability (CR) of 6.3
      dB, and light-adapted cone vision with white stimulus progressed at an average of
      0.9 dB per year with a CR of 3.8 dB. For an average patient enrolled in an early
      phase clinical trial, significant (alpha = 0.05) progression would be predicted
      to occur with 80% power in 4.5 years for rod vision and 6.1 years for cone
      vision. Localization of regions in the temporal hemifield and grouping of results
      from multiple patients would permit trial designs of shorter duration.
      Conclusions: Measurement of rod sensitivity under dark-adapted conditions
      averaged across a small region showed the greatest potential for detectability of
      progression in the shortest period.

PMID- 30208423
TI  - Confirmation of the Role of DHX38 in the Etiology of Early-Onset Retinitis
      Pigmentosa.
AB  - Purpose: Retinitis pigmentosa (RP) is a genetically heterogeneous trait with
      autosomal-recessive (ar) inheritance underlying 50% of genetic disease cases.
      Sixty-one arRP genes have been identified, and recently, DHX38 has been reported
      as a potential candidate gene for arRP with only a single family reported with a
      variant of unknown significance. We identified a missense variant in DHX38 that
      co-segregates with the arRP phenotype in two Pakistani families confirming the
      involvement of DHX38 in the etiology of early-onset RP. Methods: Exome sequencing
      was performed using two DNA samples from affected members of Pakistani families
      (MA88 and MA157) with early onset arRP. Sanger sequencing of DNA samples from all
      family members confirmed the segregation of candidate variant within both
      families. Results: A novel missense DHX38 variant c.971G>A; p.(Arg324Gln) was
      identified which segregates with the arRP phenotype and yielded a logarithm of
      the odds (LOD) score of 5.0 and 4.3 for families MA88 and MA157, respectively.
      This variant is predicted to be conserved and deleterious by several
      bioinformatics tools. Conclusions: We identified a second deleterious DHX38
      variant that segregates with arRP in two families, providing additional evidence
      that DHX38 is involved in RP etiology. DHX38 encodes for pre-mRNA splicing factor
      PRP16, which is important in catalyzing pre-mRNA splicing.

PMID- 30208425
TI  - Tracking the recognition of static and dynamic facial expressions of emotion
      across the life span.
AB  - The effective transmission and decoding of dynamic facial expressions of emotion
      is omnipresent and critical for adapted social interactions in everyday life.
      Thus, common intuition would suggest an advantage for dynamic facial expression
      recognition (FER) over the static snapshots routinely used in most experiments.
      However, although many studies reported an advantage in the recognition of
      dynamic over static expressions in clinical populations, results obtained from
      healthy participants are contrasted. To clarify this issue, we conducted a large
      cross-sectional study to investigate FER across the life span in order to
      determine if age is a critical factor to account for such discrepancies. More
      than 400 observers (age range 5-96) performed recognition tasks of the six basic
      expressions in static, dynamic, and shuffled (temporally randomized frames)
      conditions, normalized for the amount of energy sampled over time. We applied a
      Bayesian hierarchical step-linear model to capture the nonlinear relationship
      between age and FER for the different viewing conditions. Although replicating
      the typical accuracy profiles of FER, we determined the age at which peak
      efficiency was reached for each expression and found greater accuracy for most
      dynamic expressions across the life span. This advantage in the elderly
      population was driven by a significant decrease in performance for static images,
      which was twice as large as for the young adults. Our data posit the use of
      dynamic stimuli as being critical in the assessment of FER in the elderly
      population, inviting caution when drawing conclusions from the sole use of static
      face images to this aim.

PMID- 30208427
TI  - Experience-dependent long-term facilitation of skew adaptation.
AB  - Adaptation to changes in the environment allows the visual system to achieve
      optimal perception in a continuously changing visual world. One particular
      example regarding recurrently encountered changes in everyday vision is
      geometrical distortions of the environment when wearing spectacles for vision
      correction, e.g., image shear by skew geometric distortions in progressive
      additional lenses. For optimal visual performance, it would be beneficial if the
      visual system uses previous history of recurrent distortions and learns to adapt
      fast when they are reapplied, yet this has not been systematically shown. The
      present study evaluates experience-dependent long-term facilitation of fast
      adaptation to image skew, i.e., a shear from the x- and y- axis, using ecological
      stimuli. Immediate and long-term facilitation of fast adaptation induced by
      minutes time scales of extended skew exposures was tested. Fast adaptation was
      quantified via the magnitude of perceptual bias after a brief exposure to image
      skew in a constant stimulus procedure. Immediate facilitation was tested by
      comparing the magnitudes of fast adaptation that are measured on the same day
      before, i.e., baseline, and after extended skew exposure. The retention of the
      facilitation was evaluated by comparing the fast adaptation measured after, on
      average, 57 days of the previous extended skew exposure with the baseline. After
      one hour of skew exposure, the amount of fast adaptation significantly increased
      from the baseline measurement indicating immediate facilitation of the fast
      adaptation. This facilitation was retained at, on average, 57 days after the
      extended exposure. Thus, the results depicted experience dependent long-term
      facilitation of skew adaptation that potentially explains visual habituation to
      distortions of spectacles.

PMID- 30208426
TI  - Bayesian adaptive assessment of the reading function for vision: The qReading
      method.
AB  - Reading is a fundamental skill that can be significantly affected by visual
      disabilities. Reading performance, which typically is measured as reading speed
      with a reading chart, is a key endpoint for quantifying normal or abnormal
      vision. Despite its importance for clinical vision, existing reading tests for
      vision are time consuming and difficult to administer. Here, we propose a
      Bayesian adaptive method, the qReading method, for automated assessment of the
      reading speed versus print size function. We implemented the qReading method with
      a word/nonword lexical decision task and validated the method with computer
      simulations and a psychophysical experiment. Computer simulations showed that
      both the interrun standard deviation and intrarun half width of the 68.2%
      credible interval of the estimated reading speeds from the qReading method were
      less than 0.1 log10 units after 150 trials, with a bias of 0.05 log10 units. In
      the psychophysical experiment, reading functions measured by the qReading and Psi
      methods (Kontsevich & Tyler, 1999) in a word/nonword lexical decision task were
      compared. The estimated reading functions obtained with the qReading and Psi
      methods were highly correlated (r = 0.966 +/- 0.004, p < 0.01). The precision of
      the qReading method with 225 trials was comparable to that of the Psi method with
      450 trials. We conclude that the qReading method can precisely and accurately
      assess the reading function in much reduced time, with great promise in both
      basic research and clinical applications.

PMID- 30208428
TI  - Evidence for chromatic edge detectors in human vision using classification
      images.
AB  - Edge detection plays an important role in human vision, and although it is clear
      that there are luminance edge detectors, it is not known whether there are
      chromatic edge detectors as well. We showed observers a horizontal edge blurred
      by a Gaussian filter (with widths of sigma = 0.1125, 0.225, or 0.45 degrees )
      embedded in blurred Brown noise. Observers had to choose which of two stimuli
      contained the edge. Brown noise was used in preference to white noise to reveal
      localized edge detectors. Edges and noise were defined by either luminance or
      chromatic contrast (isoluminant L/M and S-cone opponent). Classification image
      analysis was applied to observer responses. In this analysis, the random
      components of the stimulus are correlated with observer responses to reveal a
      template that shows how observers weighted different parts of the stimulus to
      arrive at their decision. We found classification images for both luminance and
      isoluminant chromatic stimuli that had shapes very similar to derivatives of
      Gaussian filters. The widths of these classification images tracked the widths of
      the edges, but the chromatic edge classification images were wider than the
      luminance ones. These results are consistent with edge detection filters
      sensitive to luminance contrast and isoluminant chromatic contrast.

PMID- 30208431
TI  - Bidirectional aftereffects in perceived contrast.
AB  - It is well known that prolonged observation of a high-contrast stimulus alters
      the perception of a subsequent test stimulus. Previous studies of perceived
      contrast shifts only reported perceived contrast reductions. Here, we used
      successive presentations of test and reference stimuli and found that perceived
      contrast was reduced if tests had a lower contrast than adaptors but was
      significantly enhanced when tests had a higher contrast than adaptors. Such
      bidirectional contrast aftereffects were not observed for single adaptor flashes
      but became increasingly pronounced for repeated adaptor presentations, thereby
      suggesting that the aftereffect is a consequence of adaptation rather than of
      attentional cuing or temporal repulsion. In addition, perceived contrast
      reduction weakened as we increasingly jittered the spatial position of the
      adaptor, but perceived contrast enhancement was observed for large spatial range
      of jittered adaptor positions. We conclude that aftereffects involve adaptation
      in distinct mechanisms with narrow and broad spatial tunings. Results suggest
      that the visual system not only possesses low-level contrast encoding units,
      which monotonically increase their responses as physical contrast increases, but
      is also equipped with high-level channels selectively tuned for particular
      contrast ranges.

PMID- 30208429
TI  - Transmitting and decoding facial expressions of emotion during healthy aging:
      More similarities than differences.
AB  - Older adults tend to perform more poorly than younger adults on emotional
      expression identification tasks. The goal of the present study was to test a
      processing mechanism that might explain these differences in emotion recognition
      specifically, age-related variation in the utilization of specific visual cues.
      Seventeen younger and 17 older adults completed a reverse-correlation emotion
      categorization task (Bubbles paradigm), consisting of a large number of trials in
      each of which only part of the visual information used to convey an emotional
      facial expression was revealed to participants. The task allowed us to pinpoint
      the visual features each group used systematically to correctly recognize the
      emotional expressions shown. To address the possibility that faces of different
      age groups are differently processed by younger and older adults, we included
      younger, middle-aged, and older adult face models displaying happy, fearful,
      angry, disgusted, and sad facial expressions. Our results reveal strong
      similarity in the utilization of visual information by younger and older adult
      participants in decoding the emotional expressions from faces across ages
      particularly for happy and fear emotions. These findings suggest that age-related
      differences in strategic information use are unlikely to contribute to the
      decline of facial expression recognition skills observed in later life.

PMID- 30208430
TI  - Lateral visual occlusion does not change walking trajectories.
AB  - Difficulties with walking are often reported following brain damage that causes a
      lateralized loss of awareness on one side. Whether lateralized loss of awareness
      has a direct causal impact on walking is unknown. A review of the literature on
      visually guided walking suggests several reasons why a lateralized loss of visual
      awareness might be expected to lead to difficulties walking. Here, we isolated
      and examined the effect of lateralized vision loss on walking behavior in real
      and virtual environments. Healthy young participants walked to a target placed
      within a real room, in a virtual corridor, or on a virtual ground plane. In the
      ground-plane condition, the scene either was empty or contained three obstacles.
      We reduced vision on one side by occluding one eye (Experiment 1 and 2) or
      removing one hemifield, defined relative to either the head or trunk (Experiment
      2), through use of eye patching (Experiment 1) and a virtual-reality system
      (Experiment 2). Visual-field restrictions did not induce significant deviations
      in walking paths in any of the occlusion conditions or any of the environments.
      The results provide further insight into the visual information that guides
      walking in humans, and suggest that lateralized vision loss on its own is not the
      primary cause of walking difficulties.

PMID- 30208432
TI  - A nonvisual eye tracker calibration method for video-based tracking.
AB  - Video-based eye trackers have enabled major advancements in our understanding of
      eye movements through their ease of use and their non-invasiveness. One necessity
      to obtain accurate eye recordings using video-based trackers is calibration. The
      aim of the current study was to determine the feasibility and reliability of
      alternative calibration methods for scenarios in which the standard visual
      calibration is not possible. Fourteen participants were tested using the EyeLink
      1000 Plus video-based eye tracker, and each completed the following 5-point
      calibration methods: 1) standard visual-target calibration, 2) described
      calibration where participants were provided with verbal instructions about where
      to direct their eyes (without vision of the screen), 3) proprioceptive
      calibration where participants were asked to look at their hidden finger, 4)
      replacement calibration, where the visual calibration was performed by 3
      different people; the calibrators were temporary substitutes for the
      participants. Following calibration, participants performed a simple visually
      guided saccade task to 16 randomly presented targets on a grid. We found that
      precision errors were comparable across the alternative calibration methods. In
      terms of accuracy, compared to the standard calibration, non-visual calibration
      methods (described and proprioception) led to significantly larger errors, whilst
      the replacement calibration method had much smaller errors. In conditions where
      calibration is not possible, for example when testing blind or visually impaired
      people who are unable to foveate the calibration targets, we suggest that using a
      single stand-in to perform the calibration is a simple and easy alternative
      calibration method, which should only cause a minimal decrease in accuracy.

PMID- 30208434
TI  - Graduate Medical Education, 2017-2018.

PMID- 30208433
TI  - Eccentricity scale independence for scene perception in the first tens of
      milliseconds.
AB  - Visual processing of scenes in the first tens of milliseconds relies on global
      image summary statistics rather than localized processing. Although natural
      scenes typically involve our entire visual field, scenes are usually presented
      experimentally at limited eccentricity. Receptive-field size increases with
      foveal eccentricity while increasingly pooling activity from local receptive
      fields. Here, we asked to what extent an observer's performance on a scene-gist
      perception task depends on the contents of the scene as well as on the
      eccentricity of the scene. We manipulated the scene content by applying window
      and scotoma masks. In addition, we changed presentation eccentricity independent
      of image content by upscaling and downscaling the scenes. We find that
      discrimination is strongly affected when the scene is presented with a window of
      5 degrees , showing only the central part rather than the whole scene.
      Performance is, however, eccentricity scale independent provided that the same
      scene content is presented and a comparable area of the surface of primary visual
      cortex is activated. We furthermore show that this eccentricity scale
      independence holds for shorter presentation times, down to 17 ms in some scene
      discrimination tasks, but not for the naturalness-discrimination task.

PMID- 30208435
TI  - Medical Schools in the United States, 2017-2018.

PMID- 30208436
TI  - HIV Preexposure Prophylaxis "Smart Pill" in Early Testing.

PMID- 30208437
TI  - Heat-Activation Concentrates Chemotherapy in Liver Tumors.

PMID- 30208438
TI  - Promising Results in 18-Month Analysis of Alzheimer Drug Candidate.

PMID- 30208439
TI  - Carbapenem-Sparing Therapy for Extended-Spectrum beta-Lactamase-Producing E coli
      and Klebsiella pneumoniae Bloodstream Infection: The Search Continues.

PMID- 30208442
TI  - Forced Separation of Children From Parents: Another Consideration.

PMID- 30208440
TI  - The US Training System for Physicians-Need for Deeper Analysis.

PMID- 30208443
TI  - Biological Problems of Death.

PMID- 30208444
TI  - Lethality of Civilian Active Shooter Incidents With and Without Semiautomatic
      Rifles in the United States.

PMID- 30208445
TI  - Generational Differences in Mentoring Relationships.

PMID- 30208446
TI  - Generational Differences in Mentoring Relationships.

PMID- 30208447
TI  - Cold Agglutinins in Mycoplasma Infection.

PMID- 30208448
TI  - Antiplatelet Therapy After Coronary Artery Bypass Grafting.

PMID- 30208449
TI  - Antiplatelet Therapy After Coronary Artery Bypass Grafting.

PMID- 30208450
TI  - Generational Differences in Mentoring Relationships-Reply.

PMID- 30208451
TI  - Cold Agglutinins in Mycoplasma Infection-Reply.

PMID- 30208452
TI  - Antiplatelet Therapy After Coronary Artery Bypass Grafting-Reply.

PMID- 30208453
TI  - Association of Gestational Diabetes With Maternal Disorders of Glucose Metabolism
      and Childhood Adiposity.
AB  - Importance: The sequelae of gestational diabetes (GD) by contemporary criteria
      that diagnose approximately twice as many women as previously used criteria are
      unclear. Objective: To examine associations of GD with maternal glucose
      metabolism and childhood adiposity 10 to 14 years' postpartum. Design, Setting,
      and Participants: The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study
      established associations of glucose levels during pregnancy with perinatal
      outcomes and the follow-up study evaluated the long-term outcomes (4697 mothers
      and 4832 children; study visits occurred between February 13, 2013, and December
      13, 2016). Exposures: Gestational diabetes was defined post hoc using criteria
      from the International Association of Diabetes and Pregnancy Study Groups
      consisting of 1 or more of the following 75-g oral glucose tolerance test results
      (fasting plasma glucose >=92 mg/dL; 1-hour plasma glucose level >=180 mg/dL; 2
      hour plasma glucose level >=153 mg/dL). Main Outcomes and Measures: Primary
      maternal outcome: a disorder of glucose metabolism (composite of type 2 diabetes
      or prediabetes). Primary outcome for children: being overweight or obese;
      secondary outcomes: obesity, body fat percentage, waist circumference, and sum of
      skinfolds (>85th percentile for latter 3 outcomes). Results: The analytic cohort
      included 4697 mothers (mean [SD] age, 41.7 [5.7] years) and 4832 children (mean
      [SD] age, 11.4 [1.2] years; 51.0% male). The median duration of follow-up was
      11.4 years. The criteria for GD were met by 14.3% (672/4697) of mothers overall
      and by 14.1% (683/4832) of mothers of participating children. Among mothers with
      GD, 52.2% (346/663) developed a disorder of glucose metabolism vs 20.1%
      (791/3946) of mothers without GD (odds ratio [OR], 3.44 [95% CI, 2.85 to 4.14];
      risk difference [RD], 25.7% [95% CI, 21.7% to 29.7%]). Among children of mothers
      with GD, 39.5% (269/681) were overweight or obese and 19.1% (130/681) were obese
      vs 28.6% (1172/4094) and 9.9% (405/4094), respectively, for children of mothers
      without GD. Adjusted for maternal body mass index during pregnancy, the OR was
      1.21 (95% CI, 1.00 to 1.46) for children who were overweight or obese and the RD
      was 3.7% (95% CI, -0.16% to 7.5%); the OR was 1.58 (95% CI, 1.24 to 2.01) for
      children who were obese and the RD was 5.0% (95% CI, 2.0% to 8.0%); the OR was
      1.35 (95% CI, 1.08 to 1.68) for body fat percentage and the RD was 4.2% (95% CI,
      0.9% to 7.4%); the OR was 1.34 (95% CI, 1.08 to 1.67) for waist circumference and
      the RD was 4.1% (95% CI, 0.8% to 7.3%); and the OR was 1.57 (95% CI, 1.27 to
      1.95) for sum of skinfolds and the RD was 6.5% (95% CI, 3.1% to 9.9%).
      Conclusions and Relevance: Among women with GD identified by contemporary
      criteria compared with those without it, GD was significantly associated with a
      higher maternal risk for a disorder of glucose metabolism during long-term follow
      up after pregnancy. Among children of mothers with GD vs those without it, the
      difference in childhood overweight or obesity defined by body mass index cutoffs
      was not statistically significant; however, additional measures of childhood
      adiposity may be relevant in interpreting the study findings.

PMID- 30208457
TI  - Types of Hospitals in the United States.

PMID- 30208456
TI  - Effect of Levofloxacin Prophylaxis on Bacteremia in Children With Acute Leukemia
      or Undergoing Hematopoietic Stem Cell Transplantation: A Randomized Clinical
      Trial.
AB  - Importance: Bacteremia causes considerable morbidity among children with acute
      leukemia and those undergoing hematopoietic stem cell transplantation (HSCT).
      There are limited data on the effect of antibiotic prophylaxis in children.
      Objective: To determine the efficacy and risks of levofloxacin prophylaxis in
      children receiving intensive chemotherapy for acute leukemia or undergoing HSCT.
      Design, Setting, and Participants: In this multicenter, open-label, randomized
      trial, patients (6 months-21 years) receiving intensive chemotherapy were
      enrolled (September 2011-April 2016) in 2 separate groups-acute leukemia,
      consisting of acute myeloid leukemia or relapsed acute lymphoblastic leukemia,
      and HSCT recipients-at 76 centers in the United States and Canada, with follow-up
      completed September 2017. Interventions: Patients with acute leukemia were
      randomized to receive levofloxacin prophylaxis for 2 consecutive cycles of
      chemotherapy (n = 100) or no prophylaxis (n = 100). Those undergoing HSCT were
      randomized to receive levofloxacin prophylaxis during 1 HSCT procedure (n = 210)
      or no prophylaxis (n = 214). Main Outcomes and Measures: The primary outcome was
      the occurrence of bacteremia during 2 chemotherapy cycles (acute leukemia) or 1
      transplant procedure (HSCT). Secondary outcomes included fever and neutropenia,
      severe infection, invasive fungal disease, Clostridium difficile-associated
      diarrhea, and musculoskeletal toxic effects. Results: A total of 624 patients,
      200 with acute leukemia (median [interquartile range {IQR}] age, 11 years [6-15
      years]; 46% female) and 424 undergoing HSCT (median [IQR] age, 7 years [3-14];
      38% female), were enrolled. Among 195 patients with acute leukemia, the
      likelihood of bacteremia was significantly lower in the levofloxacin prophylaxis
      group than in the control group (21.9% vs 43.4%; risk difference, 21.6%; 95% CI,
      8.8%-34.4%, P = .001), whereas among 418 patients undergoing HSCT, the risk of
      bacteremia was not significantly lower in the levofloxacin prophylaxis group
      (11.0% vs 17.3%; risk difference, 6.3%; 95% CI, 0.3%-13.0%; P = .06). Fever and
      neutropenia were less common in the levofloxacin group (71.2% vs 82.1%; risk
      difference, 10.8%; 95% CI, 4.2%-17.5%; P = .002). There were no significant
      differences in severe infection (3.6% vs 5.9%; risk difference, 2.3%; 95% CI, 
      1.1% to 5.6%; P = .20), invasive fungal disease (2.9% vs 2.0%; risk difference, 
      1.0%; 95% CI, -3.4% to 1.5%, P = .41), C difficile-associated diarrhea (2.3% vs
      5.2%; risk difference, 2.9%; 95% CI, -0.1% to 5.9%; P = .07), or musculoskeletal
      toxic effects at 2 months (11.4% vs 16.3%; risk difference, 4.8%; 95% CI, -1.6%
      to 11.2%; P = .15) or at 12 months (10.1% vs 14.4%; risk difference, 4.3%; 95%
      CI, -3.4% to 12.0%; P = .28) between the levofloxacin and control groups.
      Conclusions and Relevance: Among children with acute leukemia receiving intensive
      chemotherapy, receipt of levofloxacin prophylaxis compared with no prophylaxis
      resulted in a significant reduction in bacteremia. However, there was no
      significant reduction in bacteremia for levofloxacin prophylaxis among children
      undergoing HSCT.

PMID- 30208461
TI  - Mumps Outbreak Preparedness.

PMID- 30208462
TI  - Gaps in HIV Testing for Black Men.

PMID- 30208459
TI  - Pumped.

PMID- 30208465
TI  - Dismissal Policies for Vaccine Refusal.

PMID- 30208466
TI  - Protecting Infants From Pertussis Disease.

PMID- 30208455
TI  - Association of Clinical, Imaging, and Thrombus Characteristics With
      Recanalization of Visible Intracranial Occlusion in Patients With Acute Ischemic
      Stroke.
AB  - Importance: Recanalization of intracranial thrombus is associated with improved
      clinical outcome in patients with acute ischemic stroke. The association of
      intravenous alteplase treatment and thrombus characteristics with recanalization
      over time is important for stroke triage and future trial design. Objective: To
      examine recanalization over time across a range of intracranial thrombus
      occlusion sites and clinical and imaging characteristics in patients with
      ischemic stroke treated with intravenous alteplase or not treated with alteplase.
      Design, Setting, and Participants: Multicenter prospective cohort study of 575
      patients from 12 centers (in Canada, Spain, South Korea, the Czech Republic, and
      Turkey) with acute ischemic stroke and intracranial arterial occlusion
      demonstrated on computed tomographic angiography (CTA). Exposures: Demographics,
      clinical characteristics, time from alteplase to recanalization, and intracranial
      thrombus characteristics (location and permeability) defined on CTA. Main
      Outcomes and Measures: Recanalization on repeat CTA or on first angiographic
      acquisition of affected intracranial circulation obtained within 6 hours of
      baseline CTA, defined using the revised arterial occlusion scale (rAOL) (scores
      from 0 [primary occlusive lesion remains the same] to 3 [complete
      revascularization of primary occlusion]). Results: Among 575 patients (median
      age, 72 years [IQR, 63-80]; 51.5% men; median time from patient last known well
      to baseline CTA of 114 minutes [IQR, 74-180]), 275 patients (47.8%) received
      intravenous alteplase only, 195 (33.9%) received intravenous alteplase plus
      endovascular thrombectomy, 48 (8.3%) received endovascular thrombectomy alone,
      and 57 (9.9%) received conservative treatment. Median time from baseline CTA to
      recanalization assessment was 158 minutes (IQR, 79-268); median time from
      intravenous alteplase start to recanalization assessment was 132.5 minutes (IQR,
      62-238). Successful recanalization occurred at an unadjusted rate of 27.3%
      (157/575) overall, including in 30.4% (143/470) of patients who received
      intravenous alteplase and 13.3% (14/105) who did not (difference, 17.1% [95% CI,
      10.2%-25.8%]). Among patients receiving alteplase, the following factors were
      associated with recanalization: time from treatment start to recanalization
      assessment (OR, 1.28 for every 30-minute increase in time [95% CI, 1.18-1.38]),
      more distal thrombus location, eg, distal M1 middle cerebral artery (39/84
      [46.4%]) vs internal carotid artery (10/92 [10.9%]) (OR, 5.61 [95% CI, 2.38
      13.26]), and higher residual flow (thrombus permeability) grade, eg, hairline
      streak (30/45 [66.7%]) vs none (91/377 [24.1%]) (OR, 7.03 [95% CI, 3.32-14.87]).
      Conclusions and Relevance: In patients with acute ischemic stroke, more distal
      thrombus location, greater thrombus permeability, and longer time to
      recanalization assessment were associated with recanalization of arterial
      occlusion after administration of intravenous alteplase; among patients who did
      not receive alteplase, rates of arterial recanalization were low. These findings
      may help inform treatment and triage decisions in patients with acute ischemic
      stroke.

PMID- 30208454
TI  - Effect of Piperacillin-Tazobactam vs Meropenem on 30-Day Mortality for Patients
      With E coli or Klebsiella pneumoniae Bloodstream Infection and Ceftriaxone
      Resistance: A Randomized Clinical Trial.
AB  - Importance: Extended-spectrum beta-lactamases mediate resistance to third
      generation cephalosporins (eg, ceftriaxone) in Escherichia coli and Klebsiella
      pneumoniae. Significant infections caused by these strains are usually treated
      with carbapenems, potentially selecting for carbapenem resistance. Piperacillin
      tazobactam may be an effective "carbapenem-sparing" option to treat extended
      spectrum beta-lactamase producers. Objectives: To determine whether definitive
      therapy with piperacillin-tazobactam is noninferior to meropenem (a carbapenem)
      in patients with bloodstream infection caused by ceftriaxone-nonsusceptible E
      coli or K pneumoniae. Design, Setting, and Participants: Noninferiority, parallel
      group, randomized clinical trial included hospitalized patients enrolled from 26
      sites in 9 countries from February 2014 to July 2017. Adult patients were
      eligible if they had at least 1 positive blood culture with E coli or Klebsiella
      spp testing nonsusceptible to ceftriaxone but susceptible to piperacillin
      tazobactam. Of 1646 patients screened, 391 were included in the study.
      Interventions: Patients were randomly assigned 1:1 to intravenous piperacillin
      tazobactam, 4.5 g, every 6 hours (n = 188 participants) or meropenem, 1 g, every
      8 hours (n = 191 participants) for a minimum of 4 days, up to a maximum of 14
      days, with the total duration determined by the treating clinician. Main Outcomes
      and Measures: The primary outcome was all-cause mortality at 30 days after
      randomization. A noninferiority margin of 5% was used. Results: Among 379
      patients (mean age, 66.5 years; 47.8% women) who were randomized appropriately,
      received at least 1 dose of study drug, and were included in the primary analysis
      population, 378 (99.7%) completed the trial and were assessed for the primary
      outcome. A total of 23 of 187 patients (12.3%) randomized to piperacillin
      tazobactam met the primary outcome of mortality at 30 days compared with 7 of 191
      (3.7%) randomized to meropenem (risk difference, 8.6% [1-sided 97.5% CI, 
      infinity to 14.5%]; P = .90 for noninferiority). Effects were consistent in an
      analysis of the per-protocol population. Nonfatal serious adverse events occurred
      in 5 of 188 patients (2.7%) in the piperacillin-tazobactam group and 3 of 191
      (1.6%) in the meropenem group. Conclusions and relevance: Among patients with E
      coli or K pneumoniae bloodstream infection and ceftriaxone resistance, definitive
      treatment with piperacillin-tazobactam compared with meropenem did not result in
      a noninferior 30-day mortality. These findings do not support use of piperacillin
      tazobactam in this setting. Trial Registration: anzctr.org.au Identifiers:
      ACTRN12613000532707 and ACTRN12615000403538 and ClinicalTrials.gov Identifier:
      NCT02176122.

PMID- 30208468
TI  - Dismissal Policies for Vaccine Refusal-Reply.

PMID- 30208469
TI  - Child Sexual Orientation and Gender Identity in the Adolescent Brain Cognitive
      Development Cohort Study.

PMID- 30208467
TI  - Association of Race/Ethnicity With Very Preterm Neonatal Morbidities.
AB  - Importance: Severe morbidity in very preterm infants is associated with profound
      clinical implications on development and life-course health. However, studies of
      racial/ethnic disparities in severe neonatal morbidities are scant and suggest
      that these disparities are modest or null, which may be an underestimation
      resulting from the analytic approach used. Objective: To estimate racial/ethnic
      differences in severe morbidities among very preterm infants. Design, Setting,
      and Participants: This population-based retrospective cohort study was conducted
      in New York City, New York, using linked birth certificate, mortality data, and
      hospital discharge data from January 1, 2010, through December 31, 2014. Infants
      born before 24 weeks' gestation, with congenital anomalies, and with missing data
      were excluded. Racial/ethnic disparities in very preterm birth morbidities were
      estimated through 2 approaches, conventional analysis and fetuses-at-risk
      analysis. The conventional analysis used log-binomial regression to estimate the
      relative risk of 4 severe neonatal morbidities for the racial/ethnic groups. For
      the fetuses-at-risk analysis, Cox proportional hazards regression with death as
      competing risk was used to estimate subhazard ratios associating race/ethnicity
      with each outcome. Estimates were adjusted for sociodemographic factors and
      maternal morbidities. Data were analyzed from September 5, 2017, to May 21, 2018.
      Main Outcomes and Measures: Four morbidity outcomes were defined using
      International Classification of Diseases, Ninth Revision, diagnosis and procedure
      codes: necrotizing enterocolitis, intraventricular hemorrhage, bronchopulmonary
      dysplasia, and retinopathy of prematurity. Results: In total, 582 297 infants
      were included in this study. Of these infants, 285 006 were female (48.9%) and
      297 291 were male (51.0%). Using the conventional approach in the very preterm
      birth subcohort, black compared with white infants had an increased risk of only
      bronchopulmonary dysplasia (adjusted risk ratio [aRR], 1.34; 95% CI, 1.09-1.64)
      and a borderline increased risk of necrotizing enterocolitis (aRR, 1.39; 95% CI,
      1.00-1.93). Hispanic infants had a borderline increased risk of necrotizing
      enterocolitis (aRR, 1.39; 95% CI, 0.98-1.96), and Asian infants had an increased
      risk of retinopathy of prematurity (aRR, 1.85; 95% CI, 1.15-2.97). In the fetuses
      at-risk analysis, black infants had a 4.40 times higher rate of necrotizing
      enterocolitis (95% CI, 2.98-6.51), a 2.73 times higher rate of intraventricular
      hemorrhage (95% CI, 1.63-4.57), a 4.43 times higher rate of bronchopulmonary
      dysplasia (95% CI, 2.88-6.81), and a 2.98 times higher rate of retinopathy of
      prematurity (95% CI, 2.01-4.40). Hispanic infants had an approximately 2 times
      higher rate for all outcomes, and Asian infants had increased risk only for
      retinopathy of prematurity (adjusted hazard ratio, 2.43; 95% CI, 1.43-4.11).
      Conclusions and Relevance: In this study, racial/ethnic disparities in neonatal
      morbidities among very preterm infants appear to be sizable, but may have been
      underestimated in previous studies, and may have implications for the future.
      Understanding these racial/ethnic disparities is important, as they may
      contribute to inequalities in health and development later in the child's life.

PMID- 30208472
TI  - The Affordable Care Act, Breastfeeding, and Breast Pump Health Insurance
      Coverage.

PMID- 30208470
TI  - Receipt of Timely Addiction Treatment and Association of Early Medication
      Treatment With Retention in Care Among Youths With Opioid Use Disorder.
AB  - Importance: Retention in addiction treatment is associated with reduced mortality
      for individuals with opioid use disorder (OUD). Although clinical trials support
      use of OUD medications among youths (adolescents and young adults), data on
      timely receipt of buprenorphine hydrochloride, naltrexone hydrochloride, and
      methadone hydrochloride and its association with retention in care in real-world
      treatment settings are lacking. Objectives: To identify the proportion of youths
      who received treatment for addiction after diagnosis and to determine whether
      timely receipt of OUD medications is associated with retention in care. Design,
      Setting, and Participants: This retrospective cohort study used enrollment data
      and complete health insurance claims of 2.4 million youths aged 13 to 22 years
      from 11 states enrolled in Medicaid from January 1, 2014, to December 31, 2015.
      Data analysis was performed from August 1, 2017, to March 15, 2018. Exposures:
      Receipt of OUD medication (buprenorphine, naltrexone, or methadone) within 3
      months of diagnosis of OUD compared with receipt of behavioral health services
      alone. Main Outcomes and Measures: Retention in care, with attrition defined as
      60 days or more without any treatment-related claims. Results: Among 4837 youths
      diagnosed with OUD, 2752 (56.9%) were female and 3677 (76.0%) were non-Hispanic
      white. Median age was 20 years (interquartile range [IQR], 19-21 years). Overall,
      3654 youths (75.5%) received any treatment within 3 months of diagnosis of OUD.
      Most youths received only behavioral health services (2515 [52.0%]), with fewer
      receiving OUD medications (1139 [23.5%]). Only 34 of 728 adolescents younger than
      18 years (4.7%; 95% CI, 3.1%-6.2%) and 1105 of 4109 young adults age 18 years or
      older (26.9%; 95% CI, 25.5%-28.2%) received timely OUD medications. Median
      retention in care among youths who received timely buprenorphine was 123 days
      (IQR, 33-434 days); naltrexone, 150 days (IQR, 50-670 days); and methadone, 324
      days (IQR, 115-670 days) compared with 67 days (IQR, 14-206 days) among youths
      who received only behavioral health services. Timely receipt of buprenorphine
      (adjusted hazard ratio, 0.58; 95% CI, 0.52-0.64), naltrexone (adjusted hazard
      ratio, 0.54; 95% CI, 0.43-0.69), and methadone (adjusted hazard ratio, 0.32; 95%
      CI, 0.22-0.47) were each independently associated with lower attrition from
      treatment compared with receipt of behavioral health services alone. Conclusions
      and Relevance: Timely receipt of buprenorphine, naltrexone, or methadone was
      associated with greater retention in care among youths with OUD compared with
      behavioral treatment only. Strategies to address the underuse of evidence-based
      medications for youths with OUD are urgently needed.

PMID- 30208473
TI  - Picosecond Laser Treatment for Acquired Bilateral Nevus of Ota-like Macules.

PMID- 30208471
TI  - Trajectories of Nevus Development From Age 3 to 16 Years in the Colorado Kids Sun
      Care Program Cohort.
AB  - Importance: Nevi are a risk factor for melanoma and other forms of skin cancer,
      and many of the same factors confer risk for both. Understanding childhood nevus
      development may provide clues to possible causes and prevention of melanoma.
      Objectives: To describe nevus acquisition from the ages of 3 to 16 years among
      white youths and evaluate variation by sex, Hispanic ethnicity, and body sites
      that are chronically vs intermittently exposed to the sun. Design, Setting, and
      Participants: This annual longitudinal observational cohort study of nevus
      development was conducted between June 1, 2001, and October 31, 2014, among 1085
      Colorado youths. Data analysis was conducted between February 1, 2015, and August
      31, 2017. Main Outcomes and Measures: Total nevus counts on all body sites and on
      sites chronically and intermittently exposed to the sun separately. Results: A
      total of 557 girls and 528 boys (150 [13.8%] Hispanic participants) born in 1998
      were included in this study. Median total body nevus counts increased linearly
      among non-Hispanic white boys and girls between the age of 3 years (boys, 6.31;
      95% CI, 5.66-7.03; and girls, 6.61; 95% CI, 5.96-7.33) and the age of 16 years
      (boys, 81.30; 95% CI, 75.95-87.03; and girls, 77.58; 95% CI, 72.68-82.81). Median
      total body nevus counts were lower among Hispanic white children (boys aged 16
      years, 51.45; 95% CI, 44.01-60.15; and girls aged 16 years, 53.75; 95% CI, 45.40
      63.62) compared with non-Hispanic white children, but they followed a largely
      linear trend that varied by sex. Nevus counts on body sites chronically exposed
      to the sun increased over time but leveled off by the age of 16 years. Nevus
      counts on sites intermittently exposed to the sun followed a strong linear
      pattern through the age of 16 years. Hispanic white boys and girls had similar
      nevus counts on sites intermittently exposed to the sun through the age of 10
      years, but increases thereafter were steeper for girls, with nevus counts
      surpassing those of boys aged 11 to 16 years. Conclusions and Relevance: Youths
      are at risk for nevus development beginning in early childhood and continuing
      through midadolescence. Patterns of nevus acquisition differ between boys and
      girls, Hispanic and non-Hispanic white youths, and body sites that are
      chronically exposed to the sun and body sites that are intermittently exposed to
      the sun. Exposure to UV light during this period should be reduced, particularly
      on body sites intermittently exposed to the sun, where nevi accumulate through
      midadolescence in all children. Increased attention to sun protection appears to
      be merited for boys, in general, because they accumulated more nevi overall, and
      for girls, specifically, during the adolescent years.

PMID- 30208474
TI  - Management of Flat Pigmented Spitz and Reed Nevi in Children.

PMID- 30208475
TI  - Immunogenicity and Safety of Monovalent Acellular Pertussis Vaccine at Birth: A
      Randomized Clinical Trial.
AB  - Importance: An alternative option to maternal vaccination to prevent severe
      pertussis in infants is vaccination at birth. Data are needed on the
      immunogenicity and safety of a birth dose of monovalent acellular pertussis (aP)
      vaccine. Objective: To compare IgG antibody responses to vaccine antigens at 6,
      10, 24, and 32 weeks of age between newborn infants receiving the aP vaccine and
      hepatitis B vaccine (HBV) or HBV alone. Design, Setting, and Participants: A
      randomized clinical trial was conducted at 4 sites in Australia (Sydney,
      Melbourne, Adelaide, and Perth) between June 11, 2010, and March 14, 2013, among
      440 healthy term (>36 weeks' gestation) infants aged less than 5 days at
      recruitment. Statistical analysis was performed from March 1, 2015, to June 2,
      2016. Intervention: Newborns received HBV and, after stratification by maternal
      receipt of adult-formulated aP-containing vaccine (tetanus toxoid, reduced
      diphtheria toxoid, and pertussis antigen content [Tdap]) prior to pregnancy, were
      block randomized to receive the aP vaccine (without diphtheria or tetanus) within
      5 days of birth or not. At 6, 16, and 24 weeks, infants received a hexavalent
      vaccine with pediatric-formulated diphtheria, tetanus and pertussis antigens
      (DTaP), Haemophilus influenzae type b (Hib), HBV, and polio vaccine, as well as
      the 10-valent pneumococcal conjugate vaccine. Main Outcomes and Measures:
      Detectable (>5 enzyme-linked immunosorbent assay units per milliliter) and
      geometric mean concentrations of IgG antibody to pertussis toxin (PT), pertactin,
      and filamentous hemagglutinin at 6, 10, and 24 weeks stratified by maternal Tdap
      history, and antibody at 32 weeks to HBV, Hib, polio, diphtheria, tetanus, and
      pneumococcal serotypes. The primary outcome was detectable IgG to both PT and
      pertactin at 10 weeks. Results: A total of 440 infants (207 girls and 233 boys;
      median gestation, 39.2 weeks) were randomized to receive the aP vaccine plus HBV
      (n = 221) or HBV only (control group; n = 219). At 10 weeks, 192 of 206 infants
      who received the aP vaccine (93.2%) had detectable antibodies to both PT and
      pertactin vs 98 of 193 infants in the control group (50.8%) (P < .001), with the
      geometric mean concentration for PT IgG 4-fold higher among the group that
      received the aP vaccine. At age 32 weeks, all infants (n = 181 with sera
      available for testing) who received the aP vaccine at birth had detectable PT IgG
      and significantly lower IgG geometric mean concentrations for Hib, hepatitis B,
      diphtheria, and tetanus antibodies. Local and systemic adverse events were
      similar between both groups at all time points. Conclusions and Relevance: The
      monovalent aP vaccine is immunogenic and safe in neonates and, if licensed and
      available, would be valuable for newborns whose mothers did not receive the Tdap
      vaccine during pregnancy. Trial Registration: http://anzctr.org.au Identifier:
      ACTRN12609000905268.

PMID- 30208476
TI  - Improving Pediatric Electronic Health Record Usability and Safety Through
      Certification: Seize the Day.

PMID- 30208477
TI  - Use of Topical Glycolic Acid Plus a Lovastatin-Cholesterol Combination Cream for
      the Treatment of Autosomal Recessive Congenital Ichthyoses.
AB  - Importance: Autosomal recessive congenital ichthyosis (ARCI) is a heterogeneous
      group of disorders caused by defects in signaling pathways involved in epidermal
      proliferation and differentiation, leading to a wide range of skin
      manifestations. Therapeutic options are limited and often unsatisfactory. Topical
      cholesterol and statin as a combined formulation has proven successful in the
      treatment of patients with CHILD syndrome (congenital hemidysplasia ichthyosis
      and limb defects). Objective: To assess change in disease severity score after a
      3-month therapeutic regimen consisting of a glycolic acid, 10% to 20%, cream and
      a combination cream of lovastatin, 2%, with cholesterol, 2%, in the treatment of
      ARCI. Design, Setting, and Participants: This case series of 15 patients with
      ARCI was conducted at the American University of Beirut, a referral center in the
      Middle East region for genodermatoses, between May 2017 and January 2018. No age
      groups were excluded; all patients were from the Middle East area; and all were
      initially not responsive to treatment with hydrating creams in combination with
      urea creams, 30% to 40%, or glycolic acid, 10% to 20%. Excluded were patients who
      had been taking systemic retinoids within 3 months before the start of the study.
      Interventions: A 3-month therapeutic regimen of glycolic acid, 10% to 20%, cream
      and a combination of lovastatin, 2%, with cholesterol, 2%, cream. Main Outcomes
      and Measures: Percentage change in disease severity scores following 2 and 3
      months of study treatment. Results: Of the 15 patients included in the study, 10
      were male (mean age, 11.2 years; age range, 2-38 years). The average percentage
      reduction in the disease severity score was 33.7% at 2 months (from 60.8 to 40.2)
      and 57.5% at 3 months (from 60.8 to 21.9). Adverse effects were mild and
      consisted mainly of irritation and burning. Conclusions and Relevance: These
      findings suggest a benefit from a treatment regimen consisting of glycolic acid,
      10% to 20%, and a combination of lovastatin, 2%, with cholesterol, 2%, in the
      treatment of ARCI. This combination of creams might also prove to be beneficial
      in other types of ichthyoses and other dermatological diseases with a defective
      skin barrier.

PMID- 30208479
TI  - Variability in Interpreting "Educational Performance" for Children With Speech
      Sound Disorders.
AB  - Purpose: Speech sound disorders (SSDs) can have a negative impact on literacy
      development, social-emotional well-being, and participation across the life span.
      Despite this, many public schools do not provide appropriate or timely services
      to this population of children. In large part, this is a result of variation in
      how state and local agencies interpret "educational performance" as outlined
      within the Individuals With Disabilities Education Act. The purpose of this study
      was to explore which educational performance factors speech-language pathologists
      (SLPs) consider when determining eligibility for children with SSDs. Method: This
      study surveyed public school SLPs to investigate how educational performance is
      interpreted for children with SSDs. Data from 575 SLPs across the United States
      are included. Results: Results supported variability in interpretation of
      educational performance within a nationwide sample of SLPs. Specifically, SLPs
      appear to consider educational performance as multidimensional. We also found
      within-state and between-states variability, indicating ambiguity in interpreting
      federal mandates. Finally, caseload size and number of years of experience were
      significantly related to which educational performance factors SLPs chose.
      Conclusion: There is significant variability across the United States with
      respect to factors considered part of educational performance for children with
      SSD. This variability reflects the general quality and specificity of guidelines
      and/or special education code published by individual states. Clinical and
      legislative recommendations are included.

PMID- 30208478
TI  - Facing the Challenges of Primary Progressive Aphasia: The Spousal Perspective.
AB  - Purpose: Primary progressive aphasia (PPA) is a cognitive-neurodegenerative
      disorder. Little is known about the personal impact PPA has on those living with
      this condition, particularly from a spousal perspective. The aim of this
      qualitative study was to gain an understanding of the personal experiences of
      spouses living with a partner diagnosed with variant forms of PPA. Method:
      Thirteen spouses whose partners were diagnosed with PPA participated in 1:1
      semistructured, in-depth interviews to explore their lived experiences of this
      illness. Using a constructivist grounded theory approach, analysis moved through
      a process of data-driven open and focused coding for the identification of
      emergent categories, themes, and subthemes that captured the challenges faced by
      spouses while supporting their partners. Results: A constructivist grounded
      theory analysis of the interview data revealed an overarching theme of "facing
      the challenges of PPA" that captured the experience spouses encountered when
      living with a partner diagnosed with PPA. Four interdependent and overlapping
      themes that sat within this overarching theme included acknowledging disconnect
      in the spousal relationship, living the decline, readjusting sense of self, and
      getting on with living. Each of these core themes revealed how spouses dealt with
      the ongoing and evolving challenges of PPA, particularly concerning changing
      relational dynamics with their partner and adjusting their own self
      conceptualization. Conclusions: Greater understanding of the spousal experiences
      of PPA is crucial to the development of intervention to help sustain spouses'
      emotional and relational connections with their partner.

PMID- 30208480
TI  - Corrected Data for Survey Results in Viewpoint.

PMID- 30208481
TI  - Diagnosing Middle Ear Pathology in 6- to 9-Month-Old Infants Using Wideband
      Absorbance: A Risk Prediction Model.
AB  - Purpose: The aim of this study was to develop a risk prediction model for
      detecting middle ear pathology in 6- to 9-month-old infants using wideband
      absorbance measures. Method: Two hundred forty-nine infants aged 23-39 weeks (Mdn
      = 28 weeks) participated in the study. Distortion product otoacoustic emissions
      and high-frequency tympanometry were tested in both ears of each infant to assess
      middle ear function. Wideband absorbance was measured at ambient pressure in each
      participant from 226 to 8000 Hz. Absorbance results from 1 ear of each infant
      were used to predict middle ear dysfunction, using logistic regression. To
      develop a model likely to generalize to new infants, the number of variables was
      reduced using principal component analysis, and a penalty was applied when
      fitting the model. The model was validated using the opposite ears and with
      bootstrap resampling. Model performance was evaluated through measures of
      discrimination and calibration. Discrimination was assessed with the area under
      the receiver operating characteristic curve (AUC); and calibration, with
      calibration curves, which plotted actual against predicted probabilities.
      Results: AUC of the fitted model was 0.887. The model validated adequately when
      applied to the opposite ears (AUC = 0.852) and with bootstrap resampling (AUC =
      0.874). Calibration was satisfactory, with high agreement between predictions and
      observed results. Conclusions: The risk prediction model had accurate
      discrimination and satisfactory calibration. Validation results indicate that it
      may generalize well to new infants. The model could potentially be used in
      diagnostic and screening settings. In the context of screening, probabilities
      provide an intuitive and flexible mechanism for setting the referral threshold
      that is sensitive to the costs associated with true and false-positive outcomes.
      In a diagnostic setting, predictions could be used to supplement visual
      inspection of absorbance for individualized diagnoses. Further research assessing
      the performance and impact of the model in these contexts is warranted.

PMID- 30208482
TI  - Information Content and Efficiency in the Spoken Discourse of Individuals With
      Parkinson's Disease.
AB  - Purpose: This study compared the information content and information efficiency
      of spoken language in individuals with Parkinson's disease (PD) to a healthy
      comparator group. Method: Nineteen participants with PD and 19 healthy older
      adults completed the prospective, cross-sectional study. In the primary analysis,
      2 language samples elicited by standardized protocols were analyzed for group
      differences using standard discourse informativeness measures including main
      events (MEs; Wright, Capilouto, Wagovich, Cranfill, & Davis, 2005) analyzed as
      %MEs and correct information units (CIUs; Nicholas & Brookshire, 1993) analyzed
      as %CIUs and CIUs/min. In exploratory analyses, the following were examined: (a)
      associations among conceptual (%MEs) and lexical (%CIUs and CIUs/min) measures
      and (b) associations among informativeness measures and age, education, disease
      severity/duration, global cognition, speech intelligibility, and a verb
      confrontation naming measure. Results: In the primary analysis, the PD group
      differed significantly from the control group on conceptual (%MEs) and lexical
      measures of content (%CIUs) and efficiency (CIUs/min). In exploratory analyses,
      for the control group %MEs were significantly correlated with CIUs/min.
      Significant associations among conceptual and lexical measures of informativeness
      were not found in the PD group. For controls, there were no significant
      correlations between informativeness measures and any of the demographic or
      speech/cognitive/language variables. In the PD group, there was a significant and
      positive association between CIUs/min and Dementia Rating Scale-Second Edition
      scores (Mattis, 2001). A significant but negative correlation was found between
      CIUs/min and motor severity scores. However, %MEs and verb naming were
      significantly and positively correlated. Conclusions: Individuals with PD without
      dementia demonstrated reduced discourse informativeness that reflects disruptions
      to both conceptual and lexical discourse processes. In exploratory analyses,
      reduced efficiency of information content was associated with global cognition
      and motor severity. Clinical and research implications are discussed within a
      Cognitivist framework of discourse production (Sheratt, 2007).

PMID- 30208483
TI  - Acquired Velopharyngeal Dysfunction: Survey, Literature Review, and Clinical
      Recommendations.
AB  - Purpose: The aim of this study was to describe the clinical assessment
      recommendations for acquired velopharyngeal dysfunction (AVPD) and, through a
      literature review and online survey, summarize current practice patterns for
      evaluation and treatment pathway determination for this target population.
      Method: An online survey to query current assessment procedures and treatment
      pathway recommendations for AVPD was developed. Following survey results, a
      literature review was completed to determine evidence-based recommendations for
      assessment procedures and intervention recommendations based on assessment
      findings. Literature search terms included the following: acquired velopharyngeal
      dysfunction, hypernasality, non-cleft velopharyngeal dysfunction, velopharyngeal
      dysfunction, velopharyngeal dysfunction AND iatrogenic, velopharyngeal
      dysfunction AND neurogenic, velopharyngeal dysfunction AND assessment OR
      evaluation, velopharyngeal dysfunction AND treatment OR intervention,
      velopharyngeal dysfunction AND practice patterns OR clinical guidelines,
      velopharyngeal insufficiency. Inclusion criteria were limited to practice
      patterns/recommendations for assessment and/or treatment recommendations for
      AVPD, English language articles published between 2000 and 2017, and peer
      reviewed journals. Studies regarding solely congenital or cleft palate
      velopharyngeal dysfunction and intervention outcome studies were excluded. Forty
      articles met inclusionary criteria. Results: The online survey results indicated
      lack of consensus for AVPD assessment and treatment recommendation protocols,
      with 93% of respondents indicating the need for a clinical guide for developing
      treatment recommendations. The majority of recommendations were filtered into an
      algorithm for clinical decision making. Conclusions: Clinical uncertainty among
      speech-language pathologists surveyed and the paucity of published clinical
      guidelines for assessing individuals with AVPD indicate the need for additional
      clinical research for this disorder, one that is heterogeneous and distinct from
      those with congenital velopharyngeal dysfunction. The proposed evidence-based
      clinical worksheet may assist in determining management for patients with AVPD
      and may serve as a starting place for validation of a clinical guideline.

PMID- 30208484
TI  - Reducing Maternal Mortality in the United States.

PMID- 30208485
TI  - Morphosyntax Production of Preschool Children With Hearing Loss: An Evaluation of
      the Extended Optional Infinitive and Surface Accounts.
AB  - Purpose: The first aim of this study was to explore differences in profiles of
      morphosyntax production of preschool children with hearing loss (CHL) relative to
      age- and language-matched comparison groups. The second aim was to explore the
      potential of extending 2 long-standing theoretical accounts of morphosyntax
      weakness in children with specific language impairment to preschool CHL. Method:
      This study examined conversational language samples to describe the accuracy and
      type of inaccurate productions of Brown's grammatical morphemes in 18 preschool
      CHL as compared with an age-matched group (+/-3 months, n = 18) and a language
      matched group (+/-1 raw score point on an expressive language subtest, n = 18).
      Age ranged from 45 to 62 months. Performance across groups was compared. In
      addition, production accuracy of CHL on morphemes that varied by tense and
      duration was compared to assess the validity of extending theoretical accounts of
      children with specific language impairment to CHL. Results: CHL exhibited
      particular difficulty with morphosyntax relative to other aspects of language. In
      addition, differences across groups on accuracy and type of inaccurate
      productions were observed. Finally, a unified approach to explaining morphosyntax
      weakness in CHL was more appropriate than a linguistic- or perceptual-only
      approach. Conclusions: Taken together, the findings of this study support a
      unified theoretical account of morphosyntax weakness in CHL in which both tense
      and duration of morphemes play a role in morphosyntax production accuracy, with a
      more robust role for tense than duration.

PMID- 30208486
TI  - The Acute Stroke Care Revolution: Enhancing Access to Therapeutic Advances.

PMID- 30208487
TI  - Communicative Accessibility in Aphasia: An Investigation of the Interactional
      Context of Long-Term Care Facilities.
AB  - Purpose: The purpose of this study was to examine the ability of persons with
      aphasia to access interaction and be included in social encounters in long-term
      care facilities (LTCFs). Method: Four persons with aphasia were the focus of this
      investigation. A qualitative research approach using ethnographic methods was
      used to conduct participant observation, semistructured interviews, and artifact
      analysis. Expanded field notes from observations, transcribed interviews, and
      artifacts were then coded to identify patterns in the data. Results: The
      interactional context of LTCFs negatively influenced the ability of persons with
      aphasia to communicate with others and develop meaningful relationships. Three
      major themes emerged from the data detailing the contextual elements leading to
      communication accessibility and inclusion: (a) lack of support, (b) social
      hierarchy, and (c) focus on performance. Conclusions: Findings highlighted
      several barriers in LTCFs that worked to discourage persons with aphasia from
      living social and expressive lives. Specific obstacles included a
      misunderstanding of aphasia and its influence on communicative exchanges and
      performance-oriented environment that overlooked psychosocial needs. Speech
      language pathologists have an important role for advocacy in LTCFs. Clinical
      implications for assessment and treatment in institutions are discussed.

PMID- 30208488
TI  - Read, Understand, Learn, & Excel (RULE): Development and Feasibility of a Reading
      Comprehension Measure for Postsecondary Learners.
AB  - Purpose: There is a lack of quick, reliable, and valid standardized reading
      comprehension assessments appropriate for postsecondary readers. We attempted to
      address this gap by designing Read, Understand, Learn, & Excel (RULE), a reading
      comprehension measure that employs sentence verification and recall tasks to
      assess reading comprehension. This article describes the exploratory study
      undertaken to construct RULE and then examines the preliminary concurrent
      validity and alternate form reliability of this measure. Method: The RULE measure
      was first developed by designing reading stimuli, test items for the sentence
      verification task, and directions for the recall test for 2 forms based on
      previous work (Griffiths, Sohlberg, Kirk, Fickas, & Biancarosa, 2016). Thirty
      undergraduate students who identified themselves as typical readers were
      administered the RULE measure as well as the Nelson-Denny Reading Test (Brown,
      Fishco, & Hanna, 1993). Students also completed questionnaires and participated
      in informal interviews to provide information regarding study and learning habits
      and academic background. Results: There was preliminary evidence of alternate
      form reliability between the sentence verification task sets of 2 chapters of
      RULE (r = .38, p < .05). Preliminary evidence for concurrent validity between
      RULE and the Nelson-Denny Reading Test was provided by correlation coefficients
      in the low to moderate range (.03-.38). Conclusion: RULE design and preliminary
      findings of concurrent validity and alternate form reliability provide "proof of
      concept" for an ecologically valid testing format that assesses comprehension
      skills appropriate for the postsecondary level. Suggestions for strengthening
      validity and reliability of the tool are provided, and clinical contributions of
      RULE are discussed. Supplemental Material: https://doi.org/10.23641/asha.6987371.

PMID- 30208490
TI  - Cardiologist Trades Stem Cells for Cell-Based Meat.

PMID- 30208489
TI  - Gadolinium Retention After Contrast-Enhanced MRI.

PMID- 30208491
TI  - Therapeutic Alternatives in the Management of Late Complications of Surgery for
      Isolated Coarctation of the Aorta.
AB  - Despite initial technical success in the treatment of coarctation of aorta, late
      recurrence and/or development of aneurysms and pseudoaneurysms frequently prompt
      reintervention. The authors hereby present such a patient whose management
      required more than a single intervention to treat his complex anatomy, and they
      discuss the therapeutic alternatives under similar circumstances.

PMID- 30208492
TI  - Aortic Dysfunction in Mitral Regurgitation Due to Floppy Mitral Valve/Mitral
      Valve Prolapse.
AB  - BACKGROUND:  Floppy mitral valve/mitral valve prolapse (FMV/MVP), a heritable
      disorder of connective tissue, often leads to mitral regurgitation (MR) and is
      the most common cause for mitral valve surgery in developed countries. Connective
      tissue disorders may affect aortic function, and a stiff aorta may increase the
      severity of MR. Aortic function, however, has not been studied in FMV/MVP with
      MR. METHODS:  A total of 17 patients (11 men, 6 women) with FMV/MVP and
      significant MR were compared with 20 controls matched for age and gender. Aortic
      diameters (AoD) were measured from left ventriculogram at 2 and 4 cm above the
      aortic valve. Aortic pressures were measured directly using fluid-filled
      catheters. Aortic distensibility was calculated using the formula: 2(systolic AoD
      diastolic AoD)/(diastolic AoD x pulse pressure). RESULTS:  Aortic distensibility
      was significantly lower in FMV/MVP compared with control at 2 cm above the aortic
      valve (1.00 +/- 0.19 versus 3.78 +/- 1.10 10-3 mm Hg-1, respectively; p = 0.027)
      and 4 cm above the aortic valve (0.89 +/- 0.16 versus 3.22 +/- 0.19 10-3 mm Hg-1,
      respectively; p = 0.007). FMV/MVP patients had greater left ventricular (LV) end
      systolic (88 +/- 72 mL versus 35 +/- 15 mL, p = 0.002) and end-diastolic (165 +/-
      89 mL versus 100 +/- 41 mL, p = 0.005) volumes, and lower LV ejection fraction,
      compared with control (50 +/- 12% versus 57 +/- 6%, p = 0.034). CONCLUSION: 
      Aortic distensibility is decreased (consistent with a stiff aorta) in patients
      with FMV/MVP and MR. A stiff aorta may increase the severity of MR. Thus,
      abnormal aortic function, which also deteriorates with age, may play an important
      role in the natural history of MR due to FMV/MVP.

PMID- 30208493
TI  - Homeopathy Seen as Personalised Nanomedicine.
AB  - Among all the discoveries of Hahnemann, potentisation was the most important,
      though controversial. The curative effect of individualised homeopathic potencies
      is empirical but inexplicable by the conventional principles of science. This
      paradox is a highly contentious topic of debate between rationalists and
      homeopaths. Recent discoveries relating to the nano-particulate nature of
      homeopathic ultra-high potencies and their potential effect on individual gene
      expression give new insights into this complex issue. It is concluded that
      homeopathy may be viewed as 'personalised nanomedicine'.

PMID- 30208494
TI  - Correction: Outcomes after endoscopic resection of large laterally spreading
      lesions of the papilla and conventional ampullary adenomas are equivalent.

PMID- 30208495
TI  - Modulation of Oxidative Stress and Hyperglycemia by Rheum spiciformis in Alloxan
      Induced Diabetic Rats and Characterization of Isolated Compound.
AB  - This study evaluates the ameliorative potential of Rheum spiciformis methanolic
      (RS-MeOH) extract in reducing oxidative stress and hyperglycemia in albino rats
      along with characterization of possible therapeutic compound(s). Groups treated
      with 50 and 100 mg/kg bw plant extract (RS-MeOH ) decrease blood glucose levels
      from 359.9+/-8.2 to 209.5+/-8.5 mg/dl (50 mg/kg bw) and 354.7+/-13.3 to 162.5+/
      7.4 mg/dl (100 mg/kg bw) on the 0th and 14th day (P<0.001) respectively. This
      reduction in blood glucose was significant as compared to glibenclamide (20
      mg/dl) which reduced glucose levels from 297.7+/-11.39 to 132.9+/-8.74 mg/dl on
      0th and 14th day respectively. Biochemical parameters triglycerdies, cholesterol,
      low density lipoprotein (LDL) and creatinine were also reduced in a dose
      dependent manner. Liver marker enzymes were positively modulated by
      administration of RS-MeOH (P<0.001). Antioxidant enzyme profile showed an
      enhanced/better pattern after the administration of RS-MeOH extracts for reduced
      glutathione, reduced glutathione (GR), glutathione peroxidase (GPx), glutathione
      S-transferase (GST) and superoxide dismutase (SOD) in both liver and pancreas.
      Moreover pancreatic histopathology reports revealed beta-cell restorative effects
      with RS-MeOH, thereby potentiating its role in improving blood glucose levels. RS
      MeOH purification and isolation studies involving GC-MS and NMR techniques
      revealed presence of emodin type compounds in RS-MeOH. Overall Rheum spiciformis
      showed ameliorative action on oxidative stress and hyperglycemia, however further
      studies to explore the mechanism of action of possible therapeutic compound in
      invivo clinical trials will prove beneficial for the advancement of new oral
      antidiabetic drug.

PMID- 30208496
TI  - A Heuristic Evaluation to Assess Use of After Visit Summaries for Supporting
      Continuity of Care.
AB  - BACKGROUND:  Outpatient providers often do not receive discharge summaries from
      acute care providers prior to follow-up visits. These outpatient providers may
      use the after-visit summaries (AVS) that are given to patients to obtain clinical
      information. It is unclear how effectively AVS support care coordination between
      clinicians. OBJECTIVES:  Goals for this effort include: (1) developing usability
      heuristics that may be applied both for assessment and to guide generation of
      medical documents in general, (2) conducting a heuristic evaluation to assess the
      use of AVS for communication between clinicians, and (3) providing
      recommendations for generating AVS that effectively support both
      patient/caregiver use and care coordination. METHODS:  We created a 17-item
      heuristic evaluation instrument for assessing usability of medical documents.
      Eight experts used the instrument to assess each of four simulated AVS. The
      simulations were created using examples from two hospitals and two pediatric
      patient cases developed by the National Institute of Standards and Technology.
      RESULTS:  Experts identified 224 unique usability problems ranging in severity
      from mild to catastrophic. Content issues (e.g., missing medical history, marital
      status of a 2-year-old) were rated as most severe, but widespread formatting and
      structural problems (e.g., inconsistent indentation, fonts, and headings;
      confusing ordering of information) were so distracting that they significantly
      reduced readers' ability to efficiently use the documents. Overall, issues in the
      AVS from Hospital 2 were more severe than those in the AVS from Hospital 1.
      CONCLUSION:  The new instrument allowed for quick, inexpensive evaluations of
      AVS. Usability issues such as unnecessary information, poor organization, missing
      information, and inconsistent formatting make it hard for patients, caregivers,
      and clinicians to use the AVS. The heuristics in the new instrument may be used
      as guidance to adapt electronic health record systems so that they generate more
      useful and usable medical documents.

PMID- 30208497
TI  - Emergency Physicians' Perceived Influence of EHR Use on Clinical Workflow and
      Performance Metrics.
AB  - OBJECTIVE:  Over the last decade, electronic health records (EHRs) have shaped
      clinical practice. In this article, we investigated the perceived effects of EHR
      use on clinical workflow and meaningful use (MU) performance metrics. MATERIALS
      AND METHODS:  Semistructured interviews were conducted with 20 (n = 20)
      physicians at two urban emergency departments. Interview questions focused on
      time spent on EHR use, changes in clinical practices with EHR use, and the effect
      of MU performance metrics on clinical workflow. Qualitative coding using grounded
      theory and descriptive analyses were performed to provide descriptive insights.
      RESULTS:  Physicians reported that EHRs improved their clinical workflow,
      especially on MU-related activities including door-to-doctor time and admit
      decision time. EHR use also affected physicians work efficiency, quality of care
      provided, and overall patient safety. CONCLUSION:  Physicians' perception of EHRs
      is likely to influence their practices. With negative perceptions of EHR
      usability problems, positive aspects of EHR use, including the influence on MU
      performance metrics, may be overridden.

PMID- 30208498
TI  - Apgar Scores at 10 Minutes and Outcomes in Term and Late Preterm Neonates with
      Hypoxic-Ischemic Encephalopathy in the Cooling Era.
AB  - OBJECTIVE:  To determine the short-term outcomes (abnormal brain magnetic
      resonance imaging [MRI]/death) in infants born with a 10-minute Apgar score of 0
      who received therapeutic hypothermia and compare them with infants with higher
      scores. STUDY DESIGN:  This is a retrospective review of 293 neonates
      (gestational age >= 35 weeks) born between November 2006 and October 2015
      admitted with hypoxic-ischemic encephalopathy who received therapeutic
      hypothermia. Results of brain MRIs were assessed by the basal ganglia/watershed
      scoring system. Short-term outcomes were compared between infants with Apgar
      scores of 0, 1 to 4, and >=5 at 10 minutes. RESULTS:  Eight of 17 infants (47%)
      with an Apgar of 0 at 10 minutes survived, having 4 (24%) without abnormalities
      on the brain MRI and 7 (41%) without severe abnormalities. There was no
      significant difference in the combined outcomes of "death/abnormal MRI" and
      "death/severe abnormalities on the MRI" between infants with Apgar scores of 0
      and 1 to 4. Follow-up data were available for six of eight surviving infants, and
      none had moderate or severe neurodevelopmental impairment. CONCLUSION:  In the
      cooling era, 47% of infants with no audible heart rate at 10 minutes and who were
      admitted to the neonatal intensive care unit survived; 24% without abnormalities
      on the brain MRI and 41% without severe abnormalities.

PMID- 30208500
TI  - Identification of a Pivotal Period in the Oral Feeding Progression of Preterm
      Infants.
AB  - OBJECTIVE:  Preterm infants are at risk of encountering oral feeding difficulties
      which impede on the transition to independent oral feeds. The objective of this
      study was to identify a pivotal period where regressions are most likely to occur
      during their oral feeding progression. STUDY DESIGN:  This is a retrospective
      study on 101 infants born <35 weeks' gestation. The sample was separated into two
      groups, infants who experienced a regression during their oral feeding
      progression and those who did not. A pivotal period was defined as a time frame
      where setbacks (a decrease in oral feed attempts by one) are most likely to occur
      at the start (1-2 oral feed attempts per day), middle (3-5 oral feed attempts per
      day), or end (6-8 oral feed attempts per day) of the oral feeding progression.
      RESULT:  Eight-two percent of infants experienced setbacks; 45% of all setbacks
      occurred at the middle time frame (p = 0.03). Infants' degree of maturity and
      enteral tube feeding intolerances were associated with increased occurrence of
      setbacks (p = 0.04). CONCLUSION:  The midpoint in the oral feeding progression is
      a pivotal period where setbacks are most likely to occur. This time frame can be
      used by clinicians to evaluate oral-motor skills for earlier provision of
      interventions to reduce the occurrence of oral feeding difficulties in this high
      risk population.

PMID- 30208499
TI  - Stillbirth and Live Birth at Periviable Gestational Age: A Comparison of
      Prevalence and Risk Factors.
AB  - OBJECTIVE:  We compared the prevalence of and risk factors for stillbirth and
      live birth at periviable gestational age (20-25 weeks). STUDY DESIGN:  This is a
      cohort study of 2.5 million singleton births in California from 2007 to 2011. We
      estimated racial-ethnic prevalence ratios and used multivariable logistic
      regression for risk factor comparisons. RESULTS:  In this study, 42% of
      deliveries at 20 to 25 weeks' gestation were stillbirths, and 22% were live
      births who died within 24 hours. The prevalence of delivery at periviable
      gestation was 3.4 per 1,000 deliveries among whites, 10.9 for blacks, 3.5 for
      Asians, and 4.4 for Hispanics. Nonwhite race-ethnicity, lower education,
      uninsured status, being U.S. born, older age, obesity, smoking, pre-pregnancy
      hypertension, nulliparity, interpregnancy interval, and prior preterm birth or
      stillbirth were all associated with increased risk of both stillbirth and live
      birth at 20 to 25 weeks' gestation, compared with delivery of a live birth at 37
      to 41 weeks. CONCLUSION:  Inclusion of stillbirths and live births in studies of
      deliveries at periviable gestations is important.

PMID- 30208501
TI  - Relocation of Maternal-Fetal Medicine Specialists in the United States.
AB  - OBJECTIVE:  To examine patterns in relocation of maternal-fetal medicine (MFM)
      specialists during the recent 10 years. STUDY DESIGN:  This descriptive study
      analyzed the migration of MFM specialists between 2006 and 2016 based on county
      locations. Year-to-year comparisons of physicians in active clinical practice
      were performed. Demographic and county characteristics were gathered from three
      data resources. A multivariable logistic regression model was used to identify
      factors associated with relocation. RESULTS:  An average of 7.4% (5.5-10.8%) of
      all 1,104 (1,103-1,115) MFM specialists moved per year. Approximately one in
      three (36%) relocated during the 10 years, usually once or twice. The likelihood
      of relocation was higher if the physician was younger, especially under 40 years
      compared with those aged 60 years and older (odds ratio [OR] = 2.08; 95%
      confidence interval [CI]: 1.36-3.19). No differences were noted based on gender
      and race/ethnicity. Physicians in independent group practices were more inclined
      to relocate, especially when compared with those in a solo or two-physician
      practice (OR = 0.38; 95% CI: 0.27-0.54). Relocations were primarily between urban
      counties (95.9%) and showed a significant regional pattern. CONCLUSION: 
      Approximately one in three MFM specialists relocated in the past 10 years, mostly
      between urban counties and especially in independent group practices.

PMID- 30208502
TI  - Diagnosis Discordance and Neonatal Transport: A Single-Center Retrospective Chart
      Review.
AB  - INTRODUCTION:  In Canada, more than 4,000 critically ill newborns per year
      require transfer. Transports are initially managed based on information conveyed
      by referral practitioners. OBJECTIVES:  To identify the frequency of diagnostic
      discordance between the referring facility, transport team, and tertiary care
      center in our outborn neonatal population and to verify the association between
      discordance events (DEs), prolonged transport stabilization times, and potential
      risk factors to further inform and facilitate the development of future outreach
      education initiatives. METHODS:  In this retrospective chart review, we
      identified and categorized DEs for patients transported by our service in a 1
      year period. Associations between DE, transport stabilization times, and patient
      variables were studied using univariate and multivariable approaches. RESULTS: 
      From 233 eligible patients, 10.7% of patients had referral to discharge
      discordance events. No significant association was identified between
      stabilization time and DE. Birth weight and presence of a neurologic diagnosis
      were associated with DE. CONCLUSION:  Diagnostic discordance was identified in 1
      of every 10 neonates transported and found to be associated with patients with
      higher birth weight and the presence of neurologic diagnoses. Outreach
      initiatives will be developed and adapted accordingly, with a focus on this
      population.

PMID- 30208503
TI  - Antibiotic Use in Pregnancy, Abnormal Fetal Growth, and Development of
      Gestational Diabetes Mellitus.
AB  - OBJECTIVE:  Antibiotics are commonly used in pregnancy. Prior studies have
      indicated that antibiotic use in pregnancy may affect birth weight, whereas data
      in nonpregnant individuals suggest that antibiotic exposure may increase diabetes
      risk. We evaluated the impact of antibiotic prescriptions during pregnancy on the
      prevalence of small for gestational age (SGA) and large for gestational age (LGA)
      birth weight and gestational diabetes mellitus (GDM). STUDY DESIGN:  This
      retrospective cohort study of 12,551 women who delivered at a large academic
      medical center between 2012 and 2014 assessed the number and type of antibiotic
      prescriptions prior to GDM testing using the electronic medical record. SGA and
      LGA birth weight and GDM rates were compared among women who were or were not
      prescribed antibiotics. RESULTS:  Overall, 3,991 (31.8%) of 12,551 patients
      received at least one antibiotic prescription. After covariate adjustment, no
      differences existed in risk of SGA (adjusted odds ratio [aOR]: 1; 95% confidence
      interval [CI]: 0.88-1.15; p = 0.94), LGA (aOR: 1; 95% CI: 0.86-1.17; p = 0.97),
      or GDM (aOR: 0.90; 95% CI: 0.72-1.13; p = 0.36) between women who were or were
      not prescribed antibiotics. CONCLUSION:  Antibiotic use does not affect the risk
      of SGA or LGA birth weight or GDM in pregnant women. These results provide
      reassurance regarding the use of antibiotics when clinically indicated in
      pregnancy.

PMID- 30208504
TI  - Implementation and Outcomes of Universal Delayed Umbilical Cord Clamping at Term.
AB  - OBJECTIVE:  To evaluate the implementation of an institutional protocol for
      universal delayed umbilical cord clamping (DCC) at term on maternal, neonatal,
      and umbilical cord blood gas outcomes. STUDY DESIGN:  This is a retrospective
      cohort study of singleton term gestations from April through July 2017. On June
      1, 2017, a protocol was implemented for DCC in all deliveries. Outcomes were
      compared between patients delivered prior to and those delivered after
      implementation. The primary outcome was postpartum hemorrhage (PPH). Secondary
      outcomes were additional adverse maternal, neonatal, and umbilical cord blood gas
      outcomes. Multivariable logistic regression was used to adjust for potential
      confounders. RESULTS:  Of 682 patients, 341 were delivered preprotocol and 341
      were delivered postprotocol. After implementation, there was 91.8% adherence to
      the protocol. Overall, there was no significant difference in PPH between
      patients delivered preprotocol and those delivered postprotocol (8.2 vs. 13.2%;
      adjusted relative risk [aRR]: 1.26, 95% confidence interval [CI]: 0.98-1.51).
      There was a significant decrease in the ability to obtain paired arterial and
      venous umbilical cord blood gases from preprotocol to postprotocol (83 vs. 63.6%;
      aRR: 0.62 [95% CI: 0.50-0.76]). There were no significant differences in abnormal
      umbilical cord blood gases or neonatal outcomes. CONCLUSION:  We did not find an
      increased risk of adverse outcomes associated with the widespread use of DCC.

PMID- 30208505
TI  - Beaded appendix.

PMID- 30208506
TI  - Migrating faecolith: an unusual case of small bowel obstruction.

PMID- 30208507
TI  - Malignant phyllodes: excellent response to neoadjuvant radiotherapy.

PMID- 30208509
TI  - Surprising image of an enterovesical fistula resulting from a perforated Meckel's
      diverticulitis.

PMID- 30208508
TI  - Immunoglobulin A anti-phospholipid antibodies in Swedish cases of systemic lupus
      erythematosus: associations with disease phenotypes, vascular events and damage
      accrual.
AB  - Immunoglobulin (Ig) G- and IgM-class anti-cardiolipin antibodies (aCL) and lupus
      anti-coagulant (LA) are included in the 1997 update of the American College of
      Rheumatology (ACR-97) systemic lupus erythematosus (SLE) criteria. Despite
      limited evidence, IgA-aCL and IgA anti-beta2 -glycoprotein-I (anti-beta2 GPI)
      were included in the 2012 Systemic Lupus International Collaborating Clinics
      criteria. The present study aimed to evaluate IgG-/IgA-/IgM-aCL and anti-beta2
      GPI occurrence in relation to disease phenotype, smoking habits, pharmacotherapy,
      anti-phospholipid syndrome (APS) and organ damage among 526 Swedish SLE patients
      meeting ACR-97. Patients with rheumatoid arthritis (n = 100), primary Sjogren's
      syndrome (n = 50) and blood donors (n = 507) served as controls. Anti
      phospholipid antibodies (aPL) were analysed by fluoroenzyme-immunoassays
      detecting aCL/anti-beta2 GPI. Seventy-six (14%) SLE cases fulfilled the Sydney
      APS-criteria, and >= 1 aCL/anti-beta2 GPI isotype (IgG/IgA/IgM) occurred in 138
      SLE patients (26%). Forty-five (9%) of the SLE cases had IgA-aCL, 20 of whom (4%)
      lacked IgG-/IgM-aCL. Seventy-four (14%) tested positive for IgA anti-beta2 GPI,
      34 (6%) being seronegative regarding IgG/IgM anti-beta2 GPI. Six (1%) had APS
      manifestations but were seropositive regarding IgA-aCL and/or IgA anti-beta2 GPI
      in the absence of IgG/IgM-aPL and LA. Positive LA and IgG-aPL tests were
      associated with most APS-related events and organ damage. Exclusive IgA anti
      beta2 GPI occurrence associated inversely with Caucasian ethnicity [odds ratio
      (OR) = 0.21, 95% confidence interval (CI) = 0.06-0.72) and photosensitivity (OR =
      0.19, 95% CI = 0.05-0.72). Nephritis, smoking, LA-positivity and
      statin/corticosteroid-medication associated strongly with organ damage, whereas
      hydroxychloroquine-medication was protective. In conclusion, IgA-aPL is not rare
      in SLE (16%) and IgA-aPL analysis may have additional value among SLE cases with
      suspected APS testing negative for other isotypes of aPL and LA.

PMID- 30208510
TI  - Human factor-designed multimodal intervention reduces the rate of unused
      peripheral intravenous cannula insertion.
AB  - OBJECTIVE: Our objective was to examine the impact of a human factor-designed
      multimodal intervention on the proportion of unused peripheral i.v. cannula
      (PIVC) insertion in our ED. METHODS: A pre- and post-multimodal intervention
      retrospective cohort study was conducted using a structured electronic medical
      record review within a single adult tertiary ED in Australia. Pre-intervention
      data was collected 30 days prior to the multimodal intervention, with 30 day post
      intervention data collected 3 months after the intervention commenced. The rates
      of PIVC inserted, the unused rate and the unused but appropriately inserted
      cannulas were the main outcome measures. RESULTS: Intravenous cannula insertion
      rates decreased by 12.9% (95% confidence interval [CI] 12.19-13.61) between the
      pre-intervention (1413/4167 [33.9%]; 95% CI 32.5-35.4) and post-intervention
      cohort (928/4421 [21.0%]; 95% CI 19.8-22.2). An analysis of 754 cases (376 pre
      intervention and 378 post-intervention) showed that 139 of 376 (37.0%; 95% CI
      32.1-42.1) i.v. cannulas were unused pre-intervention, while 73 of 378 (19.3%;
      95% CI 15.4-23.7) was unused post-intervention; an absolute reduction of 17.7%
      (95% CI 14.98-20.42). The relative risk of an unused i.v. cannula was 0.52 (95%
      CI 0.41-0.67). The proportion of unused but appropriately inserted i.v. cannulas
      remained unchanged in both cohorts, with a relative risk of 0.91 (95% CI 0.58
      1.42). CONCLUSION: Our multimodal intervention successfully reduced the number of
      unused PIVCs inserted in the ED, with a reduction in overall and unused PIVC
      insertions without any change in appropriate insertions.

PMID- 30208512
TI  - Alteration of the nucleus basalis of Meynert afferents to vibrissae-related
      sensory cortex in de-whiskered adolescent congenital hypothyroid rats.
AB  - INTRODUCTION: Thyroid hypofunction during early development results in anatomical
      alterations in the cerebellum, cerebrum, hippocampus and other brain structures.
      The plastic organization of the nucleus basalis of Meynert (nBM) projections to
      the whiskers-related somatosensory (wS1) cortex in adolescent pups with maternal
      thyroid hypofunction and sensory deprivation was assessed through retrograde WGA
      HRP labeling. METHODS: Congenital hypothyroidism induced by adding PTU (25 ppm)
      to the drinking water from embryonic day 16 to postnatal day (PND) 60. Pregnant
      rats were divided to intact and congenital hypothyroid groups. In each group, the
      total whiskers of pups (4 of 8) were trimmed continuously from PND 0 to PND 60.
      RESULTS: Following separately WGA-HRP injections into wS1, retrogradely labeled
      neurons were observed in nBM. The number of labeled neurons in nBM were higher in
      the congenital hypothyroid and whisker deprived groups compared to their controls
      (P < 0.05). CONCLUSION: Based on our results both congenital hypothyroidism and
      sensory deprivation may disturb normal development of cortical circuits in of nBM
      afferents to the wS1 cortex.

PMID- 30208511
TI  - Corrigendum to "Protection against lethal challenge by Ebola virus-like particles
      produced in insect cells" [Virology 383 (2009) 12-21].

PMID- 30208513
TI  - Preparation of cupric sulfate-based self-emulsifiable nanocomposites and their
      application to the photothermal therapy of colon adenocarcinoma.
AB  - Nanocomposites (NCs) of cupric sulfate monohydrate (CuSO4) were fabricated by hot
      melt extrusion (HME) system equipped with twin screws. Micron-sized bulk powder
      of CuSO4 was dispersed in the mixture of surfactants (Span 80 and Tween 80) and
      hydrophilic polymer (polyethylene glycol (PEG) 6000) by HME process. Reduction of
      surface tension by surfactants and homogeneous dispersion in hydrophilic polymer
      along with HME technique were introduced to prepare CuSO4 NCs. Dispersion of
      CuSO4 NCs exhibited approximately 204 nm hydrodynamic size, unimodal size
      distribution, and positive zeta potential values. Encapsulation of CuSO4 in CuSO4
      NCs and the physicochemical interactions between CuSO4 and pharmaceutical
      excipients were investigated by solid-state studies. Of note, CuSO4 NCs group
      exhibited higher antiproliferation efficacies, compared with bulk CuSO4, in Caco
      2 (human adenocarcinoma) cells at 75 and 100 MUg/mL CuSO4 concentrations (p <
      0.05). Also, near-infrared laser irradiation to CuSO4 NCs group elevated the
      antiproliferation efficacies, compared with non-irradiation group, in Caco-2
      cells. After intravenous injection in mice, CuSO4 NCs did not show severe in vivo
      toxicities. Developed CuSO4 NCs can be one of promising candidates of
      photothermal therapeutic agents for colon cancers.

PMID- 30208514
TI  - E3 ubiquitin ligase HECW2 mediates the proteasomal degradation of HP1 isoforms.
AB  - Heterochromatin protein 1 (HP1) isoforms are conserved non-histone chromatin
      binding proteins that play an important role in packaging of heterochromatin and
      gene regulation. The functions of HP1 isoforms alpha and beta are influenced by
      the nuclear lamins. Cells expressing disease-causing lamin A rod domain mutants
      show depletion of HP1alpha and beta and E3 ubiquitin ligase HECW2 is upregulated
      in these cells. However, the role of HECW2 in the turnover of HP1 proteins has
      been hitherto unexplored. Here, we show that HECW2 interacts with HP1 isoforms
      alpha and beta but not HP1gamma. Ectopic expression of HECW2 causes the
      ubiquitination of HP1alpha and beta, thereby targeting them for proteasomal
      degradation. Downregulation of HECW2 increases their steady-state levels
      indicating its role in their homeostatic regulation. Our results give important
      insights into the mechanism of proteasomal degradation of HP1 proteins in
      laminopathic cells.

PMID- 30208515
TI  - IGF-1 resist oxidative damage to HaCaT and depigmentation in mice treated with
      H2O2.
AB  - Vitiligo, an acquired pigmentary disorder of the skin, is characterized by a
      chronic and progressive loss of melanocyte from the epidermis and follicular
      reservoir. Growth factor of surrounding cells impacted on melanocytes survival.
      In this study, lower level of IGF-1 in the lesion was found than that in the
      donor area of vitiligo patients. IGF-1 improved activation of Nrf2, and inhibited
      ROS generation and endoplasmic reticulum dilation in HaCaT. C57BL/6 mice were
      treated with 5% H2O2, and combined with 50 MUg/kg of IGF-1 pre-treatment or not
      once every day for 50 consecutive days. After 50 days, IGF-1 obviously
      ameliorated depigmentation of mice skin and reduced hair follicle length, skin
      thickness and Tyrosinase induced by H2O2. Moreover, IGF-1 significantly
      suppressed CD8+ T cells infiltration in mice skin, inhibited the production of IL
      2 and IFN-gamma, and decreased the expression of CXCL10 and CXCR3. Thus, the
      results indicated that IGF-1 could resist oxidative damage to HaCaT, suppress
      CD8+ T cells infiltration and pro-inflammatory cytokines secretion, and
      suppresses the thinning of epidermal layer in vivo. It suggests that IGF-1
      inhibits oxidative damage to HaCaT and immunosuppressive effects on CD8+ T cells
      proliferation and activation to resist depigmentation induced by H2O2. This
      disclosed its multiple roles in the vitiligo, and shed a light on developing the
      application potential for IGF-1 in vitiligo.

PMID- 30208516
TI  - Excessive irisin increases oxidative stress and apoptosis in murine heart.
AB  - Irisin is an exercise-related myokine. The abundance of irisin is associated with
      many diseases, such as myocardial infarction, chronic kidney disease, metabolic
      syndrome, obesity, and diabetes mellitus. In cardiomyocytes, irisin modulates the
      mitochondrial thermogenesis, regulates ischemic responses, and affects calcium
      signaling. Previous studies suggested that irisin increases cardiomyoblast
      mitochondrial functions and protects ischemic and reperfusion injury in ex vivo
      murine heart. In human, clinical studies have shown that acute myocardial
      infarction patients with more elevated serum irisin abundances are associated
      with increased major adverse cardiovascular events. However, the mechanisms
      responsible for this discrepancy between in myocardial infarction patients and ex
      vivo murine heart is unclear. Based on the clinical observations, we hypothesized
      that excessive irisin might lead to mitochondrial dysfunctions and cardiomyocyte
      damages. Our data showed that overexpression of irisin in mice with the
      adenovirus resulted in enhanced mitochondrial respiration with a higher oxygen
      consumption rate. Enhanced irisin expression in heart and irisin treatment in
      cardiomyocytes increased reactive oxygen species production. Furthermore, irisin
      treatment in cardiomyocytes enhanced the apoptosis and the cleaved caspase 9
      levels in hypoxic condition. Pathway analysis in the murine heart with the
      overexpression of irisin showed that angiopoietin-Tie2, IL-8, IL-13, TGF-beta,
      and thrombopoietin signaling were affected by irisin. Collectively, these results
      supported that excessive irisin causes mitochondrial overdrive with a higher
      reactive oxygen species production, which results in increased apoptosis of
      cardiomyocytes in a hypoxic environment.

PMID- 30208517
TI  - Cyclic hydrostatic pressure promotes uroplakin expression in human urothelial
      cells through activation of ERK1/2 signaling.
AB  - OBJECTIVES: To investigate the effect of cyclic hydrostatic pressure on the
      expression of uroplakins and the role of extracellular regulated protein kinases
      1/2 (ERK1/2) in the hydrostatic pressure-induced uroplakin expression of human
      urothelial cells (UCs). METHODS: Human UCs were seeded into a cell culture flask
      and subjected to cyclic hydrodynamic pressures for 24 h. Pressure parameters were
      set as follows: static, 100 cm H2O, 200 cm H2O and 300 cm H2O pressure. Real-time
      polymerase chain reaction (RT-PCR) and western blot were used to detect the
      expression of uroplakins. The role of the ERK1/2 was investigated using ERK1/2
      inhibitor. RESULTS: Compared with the 0 cm H2O control group, 200 cm H2O
      hydrostatic pressure significantly increased the expression of uroplakins,
      however, 100 cm and 300 cm pressures could not promote uroplakin expression.
      Hence, ERK1/2 expression was also detected under 200 cm H2O hydrostatic pressure.
      Western blot showed that 200 cm H2O pressure promoted the expression of ERK1/2.
      ERK1/2 inhibitor decreased the pressure-induced ERK1/2 activivation and uroplakin
      expression. CONCLUSIONS: Cyclic hydrostatic pressure increases the expression of
      uroplakins via activating ERK1/2 signaling pathway in human UCs, and 200 cm H2O
      pressure may be an optimal stress parameter to promote the uroplakin expression.

PMID- 30208518
TI  - Layer-by-layer assembled PEI-based vector with the upconversion luminescence
      marker for gene delivery.
AB  - The upconversion luminescence (UCL) marker based on upconversion nanoparticles
      (UCNPs) shows unique advantages over traditional fluorescence markers, such as
      enhanced tissue penetration, better photostability, and less autofluorescence.
      Herein, we constructed a new UCL gene-delivery nonviral vector via layer-by-layer
      self-assembly of poly(ethylene imine) (PEI) with UCNPs. To reduce the
      cytotoxicity of PEI, citric acid (CA) was introduced for aqueous modification,
      and PEI assembly was introduced on the UCNP surface. Our data show that the
      nonviral vector for UCL gene-delivery demonstrates excellent photostability, low
      toxicity, and good stability under physiological or serum conditions and can
      strongly bind to DNA. Moreover, this UCL PEI-based vector could serve as a
      promising fluorescent gene-delivery carrier for theranostic applications.

PMID- 30208520
TI  - Pharmacological inhibition of Rac1 exerts a protective role in
      ischemia/reperfusion-induced renal fibrosis.
AB  - Acute kidney injury induced by renal ischemia-reperfusion (IR) is a prominent
      risk factor in the development towards renal fibrosis. Ras-related C3 botulinum
      toxin substrate 1(Rac1) has been involved in the pathophysiology of fibrotic
      disorders. But the role of Rac1 in the pathogenesis of IR-induced renal fibrosis
      is still unknown. Here, we examined the effects of NSC23766, an inhibitor of
      Rac1, on the progression of renal fibrosis after IR injury. In mice, IR induced
      Rac1 activation in kidneys. Rac1 inhibition alleviated renal damage and
      dysfunction. Mice treated with NSC23766 displayed diminished collagen area in the
      kidneys compared with IR controls, which was associated with reduction of
      extracellular matrix (ECM) proteins and alpha-SMA. Furthermore, Rac1 inhibition
      reduced profibrotic molecules levels in the kidneys of mice with IR. Finally,
      Rac1 inhibition impaired the accumulation of bone marrow-derived M2 macrophages
      and the transition of M2 macrophages to myofibroblasts. In cultured mouse
      monocytes, IL-4 treatment activated Rac1, which was abrogated by NSC23766.
      Moreover, application with IL-4 induced polarization of monocytes to M2 phenotype
      and increased the levels of ECM proteins and alpha-SMA, which was abolished by
      NSC23766. In summary, Rac1 plays a crucial role in the pathogenesis of renal
      fibrosis after IR via regulation of expressions of profibrotic molecules, bone
      marrow derived M2 macrophages recruitment, and M2 macrophages-myofibroblasts
      transition.

PMID- 30208519
TI  - Engineering of a tumor cell-specific, cytosol-penetrating antibody with high
      endosomal escape efficacy.
AB  - The main obstacles for practical uses of cytosol-penetrating peptides and
      proteins include their lack of cell- or tissue-specific targeting and limited
      cytosolic access owing to the poor endosomal escape ability. We have previously
      reported a cytosol-penetrating, human IgG1 antibody TMab4-WYW, generally referred
      to as a cytotransmab (CT), which reaches the cytosol of living cells but
      nonspecifically because it is endocytosed via a ubiquitously expressed receptor
      called heparan sulfate proteoglycan (HSPG). Here, our aim was to construct a next
      generation CT with tumor cell specificity and improved endosomal escape
      efficiency. We first substantially reduced the HSPG-binding activity of TMab4-WYW
      and then fused a cyclic peptide specifically recognizing tumor-associated
      epithelial cell adhesion molecule (EpCAM) to the N terminus of the light chain
      for EpCAM-mediated endocytosis, while maintaining the endosomal escape ability in
      the light chain variable domain (VL), thus generating epCT05. Then, we separately
      engineered another CT, dubbed epCT65-AAA, with an endosomal escape ability only
      in the heavy chain variable domain (VH) but not in VL, by functional grafting of
      the endosomal escape motif of epCT05 VL to the VH. We finally combined the heavy
      chain of epCT65-AAA and the light chain of epCT05 to create epCT65 with endosomal
      escape capacity in both the VH and VL. epCT65 effectively localized to the
      cytosol of only EpCAM-expressing tumor cells and showed approximately twofold
      improved endosomal escape efficiency, as compared with CTs with endosomal escape
      motifs in either VH or VL. The full-IgG format CT, epCT65, with a tumor cell
      specific cytosol-penetrating activity, has a great potential for practical
      medical applications, e.g., as a carrier for cytosolic delivery of payloads.

PMID- 30208521
TI  - Dual regulation of hEAG1 channels by phosphatidylinositol 4,5-bisphosphate.
AB  - The ether-a-go-go1 (EAG1, Kv10.1) K+ channel is a member of the voltage-gated K+
      channel family mainly expressed in the central nervous system and cancer cells.
      Membrane lipids regulate several voltage-gated K+ channels but their influence on
      EAG1 channels has been poorly explored. Here we have studied the regulation of
      hEAG1 channels by phosphatidylinositol 4,5-bisfofate (PIP2) by using different
      strategies to manipulate the levels of this lipid, and the patch clamp technique.
      We found that depletion of endogenous PIP2 by activation of the voltage-sensing
      phosphatase from Danio rerio (Dr-VSP) or the human muscarinic type-1 receptor
      (hM1R) inhibits hEAG1 currents; however, the application of exogenous PIP2 to
      increase the level of this lipid on the plasma membrane, also induced an
      inhibition of hEAG1. In summary, our results indicate that PIP2 have dual effects
      on hEAG1 channels and its action as activator or inhibitor depends on its initial
      level on the plasma membrane.

PMID- 30208522
TI  - Silencing of PMEL attenuates melanization via activating lysosomes and
      degradation of tyrosinase by lysosomes.
AB  - The functionally specialized melanosome is a membrane-enclosed lysosome-related
      organelle, which coexists with lysosomes in melanocytes. Pre-melanosomal protein
      (PMEL) initiates pre-melanosome morphogenesis and is the only cell-specific
      pigment protein required for the formation of fibrils on which melanin is
      deposited in melanosomes. But the effects of PMEL on melanin synthesis and
      lysosome activity remain unclear. In the study, PMEL was silenced in human
      epidermal melanocytes by siRNA transfection. Compared to the non-treated group,
      melanin content in the transfected cells was greatly reduced. Real-time qPCR,
      Western blotting and immunofluorescence analyses all showed that PMEL-siRNA
      transfection reduced protein level of tyrosinase, a key enzyme in melanogenesis,
      but it does not affect tyrosinase gene expression. Moreover, in the absence of
      PMEL, lysosomal activation was manifested by an increase in the number of
      lysosomes and activity of hydrolysis enzymes. The lysosome inhibitors restored
      tyrosinase expression after PMEL silencing, indicating that tyrosinase was
      degradated by lysosomes. The data collectively showed that silencing of PMEL
      suppressed melanization through activating lysosomes and degradation of
      tyrosinase by lysosomes. Our findings provide novel insight into the interaction
      between the melanosome and its related organelle, the lysosome, supplying a new
      idea for the pathogenesis and clinical treatment of pigmented diseases.

PMID- 30208523
TI  - The protective effects of estrogen on hepatic ischemia-reperfusion injury in rats
      by downregulating the Ang II/AT1R pathway.
AB  - BACKGROUND: Hepatic ischemia/reperfusion (I/R) injury continued to be a
      significant clinical problem. The aim of this study was to examine whether the
      protective effects of 17-estradiol (E2) on hepatic ischemia/reperfusion (I/R)
      injury was associated with the downregulation of the angiotensin II (Ang II)/AT1R
      pathway. METHODS: Forty male Sprague Dawley rats were randomized into five
      groups: Sham operation, ischemia/reperfusion (I/R), I/R + E2, I/R + E2+estrogen
      receptor antagonist ICI 182,780 (ICI), and I/R + E2+ Ang II subtype I receptor
      (AT1R) antagonist losartan (LOS) groups. A model of total hepatic I/R was
      established by portal pedicle clamping for 60 min followed by reperfusion. At
      onset of ischemia, rats were treated with vehicle, E2, or LOS. ICI was given 30
      min before E2 administration. At 24 h after reperfusion, blood samples and liver
      tissues were collected and subjected to histological examination, biochemical
      assays, and Western blot assays. RESULTS: Compared with I/R group, the degree of
      hepatocyte damage, serum ALT and TNF-alpha levels, hepatic MDA level and MPO
      activity were decreased in I/R + E2 group (all p < 0.05). Moreover, the serum and
      liver Ang II levels and hepatic AT1R protein level in I/R + E2 group were also
      significantly reduced compared with I/R group (all p < 0.05). However, the
      protective effect of E2 could be abolished by ICI administration. In contrast,
      administration of LOS conferred similar, but not as effective as E2, protective
      effects on hepatic I/R injury, without affecting Ang II and AT1R levels.
      CONCLUSIONS: The salutary effects of E2 on hepatic I/R injury are mediated in
      part by downregulating the Ang II/AT1R pathway.

PMID- 30208524
TI  - Chronic brain toxicity response of juvenile Chinese rare minnows (Gobiocypris
      rarus) to the neonicotinoid insecticides imidacloprid and nitenpyram.
AB  - Imidacloprid and nitenpyram are widely used neonicotinoid pesticides worldwide
      and were observed to adversely affect non-target aquatic organisms. In this
      study, the toxic effect of imidacloprid and nitenpyram on the brain of juvenile
      Chinese rare minnows (Gobiocypris rarus) was investigated by determining the
      oxidative stress, 8-hydroxy-2-deoxyguanosine (8-OHdG) content and
      acetylcholinesterase (AChE) activity. The superoxide dismutase (SOD) activities
      did not significantly change after long-term exposure to imidacloprid and
      nitenpyram. A noticeable increase of catalase (CAT) activities was observed on
      the brain tissues under 0.1 mg/L imidacloprid and under all nitenpyram treatments
      (p < 0.05). The malondialdehyde (MDA) content increased markedly under 2.0 mg/L
      imidacloprid and 0.1 mg/L nitenpyram treatments (p < 0.05). The glutathione (GSH)
      content in the brain significantly increased under 0.5 and 2.0 mg/L imidacloprid
      (p < 0.05). A significant decrease was observed in the mRNA levels of Cu/Zn-sod
      under 2.0 mg/L imidacloprid and those of cat under 0.1 and 0.5 mg/L nitenpyram (p
      < 0.05). The mRNA levels of gpx1 clearly decreased under 2.0 mg/L imidacloprid
      and under 0.1 mg/L nitenpyram (p < 0.05). The treatments of 0.1 and 0.5 mg/L
      nitenpyram decreased cat expression levels markedly (p < 0.05). 2.0 mg/L
      imidacloprid raised the 8-OHdG content. The AChE activities increased markedly
      under 0.5 and 2.0 mg/L imidacloprid while clearly decreasing under 2.0 mg/L
      nitenpyram (p < 0.05). Therefore, our results indicate that imidacloprid and
      nitenpyram might cause adverse effects on juvenile Chinese rare minnows brain.
      Notably, imidacloprid had greater impacts on juvenile rare minnows compared to
      nitenpyram.

PMID- 30208525
TI  - Turn bane into a boon: Application of invasive plant species to remedy soil
      cadmium contamination.
AB  - Cadmium (Cd) is one of the mostly hazardous soil pollutants and has threatened
      human health by accumulating in grains of crops. Phytoremediation is a promising
      technique to remedy soil Cd contamination, but reported Cd hyperaccumulators
      remain limited. In this study, we explored potential applicability of three
      invasive plant species (Chromolaena odorata, Bidens pilosa and Praxelis
      clematidea) to remove soil Cd using greenhouse experiment. Results showed that
      the three species grew well with Cd treatments compared to the controlled
      individuals, suggesting that the species had high Cd tolerance by physiological
      adjustments such as up-regulating the antioxidant enzyme activities. The only
      exception was that the height of P. clematidea in the 60 mg kg-1 Cd treatment was
      less than that in the control. Within the tested Cd concentration range, the C.
      odorata exhibited high bioaccumulation characteristics that meet the recommended
      standards to identify as a hyperaccumulator (shoot Cd concentration > 100 mg kg-1
      with bioconcentration and transfer factors > 1). The other two species had also
      the shoot bioconcentration factor and transfer factor greater than one, while the
      shoot Cd concentration was relatively lower. Our results highlight a potential
      applicability of the invasive species used in this study for remediation of the
      soil Cd contamination, which turns bane into a boon.

PMID- 30208526
TI  - Safety and quality of the green tide algal species Ulva prolifera for option of
      human consumption: A nutrition and contamination study.
AB  - This study sampled U. prolifera and surface seawater from the same locations
      where green tide broke out in the southern Yellow Sea, in both the year 2016 and
      2017. The revealed nutritive components of U. prolifera samples characterized U.
      prolifera as a high-protein, high-Fe, high ratio of unsaturated lipid acids and
      low-fat seaweed food, with an ideal ratio of essential and nonessential amino
      acids. The concentrations and health risk assessment of major micropollutants
      (heavy metals, pesticides and polycyclic aromatic hydrocarbon (PAHs)) in U.
      prolifera were also analyzed, respectively. The results showed that the Target
      Hazard Quotient values of five heavy metals (<1.0 * 10-1) and the total hazard
      index of 13 pesticides (<1.5 * 10-8) were lower than the unity, respectively, and
      the incremental lifetime cancer risk values of PAHs (<7.4 * 10-7) were lower than
      the USEPA limit (1.0 * 10-6). It suggested that consuming U. prolifera is safe as
      a food-source option, with PAHs causing relatively higher risks. PAHs from the
      sites closer to the shore were also found more originated from pyrolysis. We
      further confirmed the PAH congeners were partly in equilibrium between seawater
      and U. prolifera. It suggested the possibility that the food safety-risk turned
      to be above the USEPA limit was not high regardless of the sample collecting
      time. However, the sources of PAHs and their contributions to the accumulation in
      U. prolifera need further investigation. This study favored that U. prolifera of
      the green tide from the southern Yellow Sea has a potential for a nutritious-food
      production.

PMID- 30208527
TI  - Heavy metals accumulation in soil after 4 years of continuous land application of
      swine manure: A field-scale monitoring and modeling estimation.
AB  - Land application of animal manure has been encouraged widely in China. This
      presents a risk of heavy metals (HMs) accumulation in the soil due to their high
      contents in the feeds and additives. A 4-year field-scale study was conducted to
      monitor and estimate HMs accumulation in the soil with land application of swine
      manure. The results show a clear tendency for As, Hg, Cr, Cu, Zn and Mn to
      increase gradually with the application duration, yielding an average annual
      increase of 0.57, 0.011, 6.20, 5.64, 22.58, and 23.45 mg kg-1, respectively, at
      the annual application rate of about 250 t ha-1 of swine manure. The estimation
      from the mass balance modeling indicates the environmental risk of Cd, Cu and Zn
      will exceed the threshold levels for agricultural soils in China in the next 10
      50 years. Determination of a suitable application rate of animal manure would be
      the first consideration for mitigating the environmental risk of HMs currently.

PMID- 30208528
TI  - Urinary vanadium concentration in relation to premature rupture of membranes: A
      birth cohort study.
AB  - Heavy metal exposure has been indicated to be linked with reproductive and
      developmental toxicity. However, human studies on the association between heavy
      metal exposure and premature rupture of membranes (PROM) are limited. Thus, we
      aimed to evaluate the associations between urinary metal concentrations in
      pregnant women and the risk of PROM. The study was conducted among 7290 pregnant
      women from an ongoing cohort study in China. Levels of urinary metals were
      determined using an inductively coupled plasma-mass spectrometry and adjusted by
      creatinine concentration (MUg/g creatinine). Adjusted odds ratios (OR) and 95%
      confidence intervals (CI) for PROM and preterm PROM were estimated using logistic
      regression models. Among 12 urinary metals detected, vanadium (V) have shown
      stable positive associations with PROM and preterm PROM. With one unit increase
      in natural logarithmically transformed urinary V concentration, adjusted OR of
      1.57 (95% CI: 1.47, 1.66) for PROM was observed. Compared with the lowest tertile
      of urinary V, we also observed positive associations between V levels and PROM
      (for the medium tertile, adjusted OR = 1.66, 95% CI: 1.34, 2.05; for the highest
      tertile, adjusted OR = 3.75, 95% CI: 3.09, 4.54). In addition, higher adjusted
      ORs for preterm PROM were observed (for the highest tertile, adjusted OR = 8.14,
      95% CI: 4.55, 14.55). Further stratified analysis suggested the associations were
      more pronounced among women delivering male infants than those with female
      infants. Our present epidemiological study indicated that pregnant women exposure
      to higher level of V might lead to an increased risk of PROM.

PMID- 30208529
TI  - Species-dependent toxicity, accumulation, and subcellular partitioning of cadmium
      in combination with tetrabromobisphenol A in earthworms.
AB  - Cadmium (Cd) and tetrabromobisphenol A (TBBPA) are two ubiquitous pollutants in
      soils and are often found together at electronic waste recycling sites. In this
      study, their toxicity as well as the accumulation and subcellular partitioning of
      Cd were determined in two ecologically different earthworms Eisenia fetida and
      Metaphire guillelmi exposed for 14 days to Cd (1 mg kg-1) and TBBPA (10, 50, 100,
      and 500 mg kg-1) alone and in combination. In general, Cd-TBBPA co-exposure
      resulted in synergistic effects in terms of acute toxicity, growth inhibition,
      histopathological changes in body walls, and oxidative stress responses to
      earthworms, moreover, M. guillelmi showed higher sensitivity than E. fetida.
      Principal component analysis showed that the two earthworm species differed in
      their biomarker expression patterns. In addition, Cd accumulation was
      significantly (P < 0.01) reduced in E. fetida co-exposed to TBBPA but
      significantly (P < 0.05 and 0.01) enhanced in M. guillelmi. The difference in
      bioaccumulation between the two earthworm species may be made by their different
      exposure routes despite the decrease of Cd bioavailability (assessed by the
      diffusive gradients in thin films technique) in the soils. High doses of TBBPA
      also altered the subcellular distribution of Cd in the earthworms. These findings
      demonstrate the need to include more ecologically relevant earthworm species,
      represented in this study by M. guillelmi, in soil risk assessments of Cd and
      TBBPA co-exposure.

PMID- 30208530
TI  - Performances and structures of functional microbial communities in the mono azo
      dye decolorization and mineralization stages.
AB  - Removal of azo dye from wastewater with biological method is a complicated
      process, including decolorization and mineralization. However, there is little
      understanding of the functional microbial community involved in the whole dye
      degradation process. In this study, a simplified model using anaerobic3-oxic2
      sedimentaion reactor was proposed. Acid Orange and Methyl Orange were treated as
      model azo dyes. In each compartment, the degradation intermediates of azo dyes
      were identified with UV-Vis, FTIR, HPLC-MS and GC-MS, and the corresponding
      microorganisms were determined with 16S rDNA high throughput Miseq sequencing.
      Decolorization happened in anaerobic compartments, while mineralization of the
      resulted aromatic amines mainly occurred under aerobic circumstance. LEfSe
      analysis demonstrated that the microbial community compositions were
      significantly influenced by the chemical structures of substrates. With t-value
      biplot, the relationship between azo dye degradation and microbial community
      structure was proposed statistically. It was found that the functional microbial
      communities varied with the change of azo dye degradation intermediates. Besides,
      cleavage of benzene ring also happened under anaerobic circumstance. This may be
      due to the genera of Parabacteroides and Bacteroides, which exhibited
      significantly positive relationships with 1,4-Benzenediol. With the new model,
      the performances and structures of functional microbial communities for NN-
      reduction and aromatic amines mineralization were characterized and the reaction
      mechanism was explored.

PMID- 30208531
TI  - Multi-walled carbon nanotube/amino-functionalized MIL-53(Fe) composites:
      Remarkable adsorptive removal of antibiotics from aqueous solutions.
AB  - A novel adsorbent composite was synthesized by combining amino-functionalized MIL
      53(Fe) with multi-walled carbon nanotubes (MWCNT), and used to adsorb
      tetracycline hydrochloride (TCN) and chlortetracycline hydrochloride (CTC). The
      maximum adsorption capacities of TCN and CTC over MWCNT/NH2-MIL-53(Fe) at 25 
      degrees C were 368.49 and 254.04 mg g-1, which are, respectively, 1.79 and 8.37
      times higher than that of chaff biochar. Interestingly, the mesoporosity of
      MWCNT/NH2-MIL-53(Fe) significantly increased through introduction of MWCNT into
      NH2-MIL-53(Fe), which proved to be favorable for the production of active
      adsorption sites. Besides, the remarkably increased adsorption capacity can be
      ascribed to the hydrogen bonding between amino functional groups on MWCNT/NH2-MIL
      53(Fe) and hydroxyl functional groups on TCN or CTC. Moreover, the pi-pi
      interaction between adsorbate and adsorbent was considered the main reason for
      the adsorption of TCN and CTC. The great adsorption capacity, as well as
      excellent reusability, demonstrated the potential application of MWCNT/NH2-MIL
      53(Fe) in the removal of TCN and CTC from aqueous solutions.

PMID- 30208532
TI  - Human activities altered water N:P ratios in the populated regions of China.
AB  - Being able to quantify nutrient stoichiometry in the waterbodies is especially
      important given its strong effects on a variety of ecological processes. China
      has made huge progress in the improvement of surface water quality, but the
      accompanying changes to water nutrient stoichiometry and implications are not
      well understood yet. Our results have shown that the water nutrient cycles have
      been decoupled in China's populated regions, and population density and GDP
      values in the same catchment are useful in explaining the variances of lake N:P
      stoichiometry in East China Lake Region. In other regions, water N and P tend to
      respond to the selected parameters in a similar way, leading to the poor
      prediction of N:P stoichiometry. With the progress of water management in China,
      a similar change of water nutrients and their stoichiometry as the developed
      countries is occurring, i.e., faster decrease of TP concentrations than TN, and
      continuing increase of N:P ratios. It is necessary for the managers to be aware
      of the quick and large-scale changes of nutrient stoichiometry in the water,
      since the ecological risk caused by the changes to the aquatic systems is still
      not well known.

PMID- 30208533
TI  - Immune and xenobiotic response crosstalk to chemical exposure by PA01 infection
      in the nematode Caenorhabditis elegans.
AB  - Most organisms simultaneously face various chemical and biological stresses in
      the environment. Herein, we investigated how pathogen infection modifies an
      organism's response to chemical exposure. To explore this phenomenon, we
      conducted a toxicity study combined with pathogen infection by using the nematode
      Caenorhabditis elegans, the pathogen Pseudomonas aeruginosa, and various
      environmental chemicals. C. elegans preinfected with PA01, when subsequently
      exposed to chemicals, became sensitized to the toxicity of nonylphenol (NP) and
      cadmium (Cd), whereas they became tolerant to the toxicity of silver
      nanoparticles (AgNPs); this led us to conduct a mechanistic study focusing on
      AgNP exposure. A gene expression profiling study revealed that most of the immune
      response genes activated by PA01 infection remained activated after subsequent
      exposure to AgNPs, thereby suggesting that the acquired tolerance of C. elegans
      to AgNP exposure may be due to boosted immunity resulting from PA01 preinfection.
      Further, a functional genetic analysis revealed that the immune response pathway
      (i.e., PMK-1/p38 MAPK) was involved in defense against AgNP exposure in PA01
      preinfected C. elegans, thus suggesting immune and stress response crosstalk to
      xenobiotic exposure. This study will aid in the elucidation of how pathogen
      infection impacts the way the defense system responds to subsequent xenobiotic
      exposure.

PMID- 30208534
TI  - Trace elements in atmospheric wet precipitation in Detroit metropolitan area:
      Levels and possible sources.
AB  - Rain and snow samples were collected in the Detroit metropolitan area and
      analyzed by inductively coupled plasma-mass spectrometry (ICP-MS). Twenty-two
      elements were detected in a concentration range from ~0.03 to ~1.8 * 103 MUg/kg.
      An enrichment factor (EF), defined as, EF=(X/Al)sample(X/Al)crust , was estimated
      for each element (X) detected, and used to determine possible origins of the
      element. Based on the hypothesis that crustal material is the only source of
      aluminum (Al) found in the atmospheric environment, an EF value near unity for an
      element suggests that crustal material is a major source of this element. If
      EF>10, an element is enriched in the atmosphere relative to its concentration in
      the earth's crust, implying a source other than the crust. Alkali, alkaline earth
      and lanthanide metals detected in the samples exhibit low EF values, indicating
      mainly a crustal source. Six elements (As, Cd, Cu, P, Pb and Zn) were
      significantly enriched in the samples as their EF values were greater than 10,
      thus originated likely from anthropogenic emissions. The relative order of the
      significantly enriched elements is estimated as follows: Cd > Pb > Zn > As > Cu >
      P. A high enrichment (EF~100) for phosphorus was observed and caused plausibly by
      extensive usage of phosphorus-containing fertilizers and pesticides.

PMID- 30208535
TI  - Rapid removal of sulfamethoxazole from simulated water matrix by visible-light
      responsive iodine and potassium co-doped graphitic carbon nitride photocatalysts.
AB  - An environment-friendly iodine and potassium co-doped g-C3N4 (IKC3N4)
      photocatalyst was synthesized via the co-pyrolysis of urea and potassium iodate.
      Various characterization techniques were employed to evaluate the physical,
      thermal and chemical characteristics of the as-synthesized photocatalyst.
      Sulfamethoxazole (SMX) was used as a representative antibiotic pollutant. SMX
      removal by IK-C3N4 photocatalysts exceeded 99% (~23 times higher than that of
      pure g-C3N4) within 45 min of visible light irradiation. The kinetics of SMX
      removal was analyzed with respect to solution pH, photocatalyst dosage and
      initial SMX concentration. Experimental data was found to fit the pseudo-first
      order kinetics and the Langmuir-Hinshelwood kinetics. The reuse of the
      photocatalyst up to 3 consecutive photodegradation cycles gave a minimal decline
      in SMX removal while the structure and the crystallinity of the nanomaterials
      remained unchanged. Overall, morphology engineering of conventional bulk
      graphitic carbon nitride can produce highly efficient photocatalysts for the
      decontamination of antibiotics in the aqueous environment.

PMID- 30208536
TI  - Uptake, distribution and elimination of chemicals in fish - Which physiological
      parameters are the most relevant for toxicokinetics?
AB  - Bioconcentration and toxicity studies are regularly conducted for the risk
      assessment of chemicals. If such tests yield different results for different fish
      species, this can either be due to differences in toxicokinetics or to
      differences in toxicodynamics. Here we investigate which physiological parameters
      could cause major differences in the toxicokinetics in fish. To this end it is
      important to distinguish physiological parameters that affect the sorption
      capacity of the fish from those that affect kinetic processes. Variability in the
      lipid content of a fish is the most influential parameter for the sorption
      capacity of fish and therefore most relevant for the total concentration in fish
      under steady-state conditions when metabolism is not relevant. In terms of
      kinetics, ventilation rate, uptake efficiency from food and metabolism are the
      most influential factors. While ventilation rate can roughly be estimated from
      allometric scaling equations, little general information is available on the
      uptake efficiency from food. The metabolism rate constant appears to be the
      single most influential toxicokinetic factor. This information cannot be
      estimated but must be determined experimentally, preferably from in vitro
      experiments.

PMID- 30208537
TI  - The accelerated biodegradation and mineralization of acetaminophen in the H2O2
      stimulated upflow fixed-bed bioreactor (UFBR).
AB  - The biodegradation and mineralization of acetaminophen (ACT) was evaluated in the
      upflow fixed-bed bioreactor (UFBR) inoculated with a biomass containing mixture
      of Pseudomonas spp. and Bacillus spp. as the dominant bacteria under H2O2
      stimulation. The effect of various main operational variables was evaluated on
      the performance of the UFBR for ACT removal. The maximum ACT removal was obtained
      at the H2O2:ACT molar ratio of 14. H2O2 induced the bacteria in biofilm for the
      in-situ generation of peroxidase resulted in the acceleration of ACT
      decomposition into more biodegradable intermediates. Over 99% of ACT and 72% of
      its TOC at initial ACT concentrations up to 300 mg/L could be eliminated under
      optimum H2O2:ACT molar ratio in the batch UFBR within 12 h recirculation time.
      The specific biodegradation rate of ACT increased from 1.0 to 4.1 mg
      ACT/gbiomass.h when the inlet loading rate was increased from 8.3 to 41.7 g
      ACT/m3.h. In addition, the complete biodegradation and TOC removal of ACT was
      observed in the continuous UFBR at the hydraulic retention time of 6 h and the
      presence of 1-20 g/L salinity without inhibition. The presence of H2O2 could
      efficiently stimulate the production of bacterial peroxidase, which in turn
      resulted in the acceleration of ACT biodegradation and mineralization. Therefore,
      the H2O2-stimulated UFBR is an efficient and viable technique for in-situ
      production of peroxidase used for acceleration of ACT biodegradation.

PMID- 30208538
TI  - Critical review of major sources of human exposure to N-nitrosamines.
AB  - More than 24 N-nitrosamine compounds contribute to the total N-nitrosamine (TNA)
      burden monitored routinely to assess human exposure to this important group of
      known and suspected human carcinogens. A literature review (n = 122) identified
      multiple sources of human exposure to TNAs, including waters (40 +/- 10.5 ng/L;
      average +/- standard deviation), food and beverages (6.7 +/- 0.8 ng/g), tobacco
      (16,100 +/- 3650 ng/g) and personal care products (1500 +/- 750 ng/g). Due to
      source control interventions, levels of TNAs in beer have dropped by about 96%
      between 1980 and 1990, whereas N-nitrosamine levels in other known sources have
      shown little to no change. Maximum daily TNA exposure in the U.S. in units of
      ng/d is estimated at 25,000 +/- 4,950, driven by consumption of tobacco products
      (22,000 +/- 4350), food (1900 +/- 380), alcohol (1000 +/- 200), and drinking
      water (120 +/- 24). Behavioral choices of individuals in non-occupational
      settings were calculated to result in a spectrum of exposure values ranging from
      a lower bound of 1900 +/- 380 ng/d to a higher bound of 25,000 +/- 4950 ng/d,
      indicating opportunities for a possible 12-fold reduction in TNA exposure to 8%
      of the above maximum through deliberate choices in diet and lifestyle.

PMID- 30208539
TI  - Total mineralization of mixtures of Tartrazine, Ponceau SS and Direct Blue 71 azo
      dyes by solar photoelectro-Fenton in pre-pilot plant.
AB  - Mixtures of monoazo Tartrazine, diazo Ponceau SS and triazo Direct Blue 71 dyes
      with 105 mg L-1 of total organic carbon (TOC) in 0.050 M Na2SO4 at pH 3.0 have
      been treated by solar photoelectro-Fenton (SPEF). Experiments were carried out in
      a 2.5 L pre-pilot plant with a Pt/air-diffusion cell coupled to a solar planar
      photoreactor. Comparative trials were made by anodic oxidation with
      electrogenerated H2O2 (AO-H2O2) and electro-Fenton (EF) to better understand the
      role of oxidizing agents. AO-H2O2 gave poor degradation due to the low oxidation
      ability of OH formed at the Pt anode and H2O2 produced at the cathode. Similar
      color removal was achieved in EF and SPEF because the main oxidant was OH formed
      in the bulk from Fenton's reaction. EF yielded partial mineralization by
      formation of molecules with high stability against OH. In contrast, these by
      products were rapidly photolyzed under sunlight irradiation in SPEF, which was
      the most powerful treatment. Up to 8 linear final carboxylic acids were detected,
      along with the release of sulfate and ammonium ions. The effect of Fe2+ and azo
      dye concentrations, and current density over the SPEF performance was assessed.
      Total mineralization of azo dyes mixtures occurred when operating up to 105 mg L
      1 TOC with 0.50 mM Fe2+ at 100 mA cm-2.

PMID- 30208540
TI  - Performance and toxicity assessment of nanoscale zero valent iron particles in
      the remediation of contaminated soil: A review.
AB  - Nanoscale zero valent iron (nZVI) particles have been studied in recent years as
      a promising technology for the remediation of contaminated soil. Although the
      potential benefits of nZVI are considerable, there is a distinct need to identify
      possible risks after environmental exposure to nZVI. This work firstly introduced
      the remediation of nZVI for heavy metals and chlorinated organic compounds in
      contaminated soil. And the corresponding stabilization mechanisms were discussed.
      We also highlighted the factors affecting nZVI reactivity, including nZVI surface
      area, nZVI stabilizers, soil pH, soil organic matter and soil types. In addition,
      this review shows a critical overview of the current understanding of toxicity of
      nZVI particles to soil bacteria and fungi. The toxicity mechanisms, cellular
      defenses behaviors and the factors affecting the toxicity of nZVI were
      summarized. Finally, the remaining barriers to be overcome in materials
      development for environment application are also discussed.

PMID- 30208541
TI  - Remediation of hexavalent chromium in contaminated soil by Fe(II)-Al layered
      double hydroxide.
AB  - In this study, high-efficiency and low-cost Fe(II) and Al(III) layered double
      hydroxide (Fe-Al-LDH) was synthesized and used for the remediation of Cr(VI)
      contaminated soil. The Fe-Al-LDH characteristics were analyzed with different
      techniques. The results of X-ray diffraction (XRD) and transmission electron
      microscopy (TEM) analyses revealed its highly crystalline structure with sheet
      morphology, and a Brunauer-Emmett-Teller (BET) surface area of 46.85 m2/g. In
      addition, the remediation tests indicated that adding 1 g/L of Fe-Al-LDH to a
      solution of Cr(VI)-contaminated soil, at a soil to solution ratio of 1 g: 5 mL,
      completely immobilized the pre-adsorbed Cr(VI) in the soil (2079.84 mg/kg).
      Additionally, the Fe-Al-LDH could be used in a wide range of pH conditions and no
      Cr(VI) was detected in the leaching solution. Based on the characterization of X
      Ray Diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy,
      inductively coupled plasma mass spectrometry (ICP-MS), and X-ray photoelectron
      spectroscopy (XPS) analysis, it is proposed that adsorption and reduction may be
      involved in the mechanism of Cr(VI) immobilization by Fe-Al-LDH. At the beginning
      of the reaction, Cr(VI) entered the layer structure of the LDH or was adsorbed on
      the surface of the LDH. Then, Fe(II) was involved in reducing the Cr(VI) to
      Cr(III) and was oxidized to Fe(III). Part of the Cr(VI) and Cr(III) were co
      precipitated with Fe(III) and Al (III) during the formation of iron oxide or
      hydroxide.

PMID- 30208543
TI  - Spatiotemporal trends in PM2.5 levels from 2013 to 2017 and regional demarcations
      for joint prevention and control of atmospheric pollution in China.
AB  - The promulgation and implementation of the Air Pollution Prevention and Control
      Action Plan (APPCAP) have greatly accelerated air quality improvements in China.
      In this study, these improvements were assessed and analyzed using arithmetic
      mean and percentile methods. Air quality status and trends were illustrated
      meticulously. Air pollution risks remaining since the implementation of the
      APPCAP were also identified. In addition, a complex network correlation model was
      created and used to demarcate highly inter-correlated regions within China, which
      were identified using long-term PM2.5 concentration data. The results indicate
      that the annual mean PM2.5 concentration decreased by more than 30% throughout
      the country since the implementation of the APPCAP. However, more than 1 billion
      people were still exposed to polluted air containing PM2.5 concentrations
      exceeding the WHO Interim Target-1 (WHO IT-1). Cities with populations of more
      than 10 million were generally among the most polluted regions in China, while
      PM2.5 concentrations in locations with populations of less than 1 million met WHO
      IT-1 standards. Moreover, PM2.5 network correlation analysis defined 7 key Joint
      Prevention and Control of Atmospheric Pollution (JPCAP) regions with strong
      synchronicity in PM2.5 mass concentrations; these results suggest that JPCAP
      could be implemented separately with in each of these demarcated regions. The
      atmospheric pollution control concepts and methods proposed herein are also
      broadly applicable for the implementation of JPCAP policies in other regions
      worldwide.

PMID- 30208542
TI  - Distribution and predictors of 20 toxic and essential metals in the umbilical
      cord blood of Chinese newborns.
AB  - Early-life exposure to heavy metals and/or trace metal imbalances can have
      negative developmental effects. Here we sought to characterize exposure profiles
      for 20 heavy metals and trace elements in umbilical cord blood plasma and
      identify demographic predictors of exposure. Twenty metals were measured in cord
      plasma from 357 Chinese infants using ICP-MS. Relationships between demographic
      variables and metals were analyzed using generalized linear models and logistic
      regression. Ten metals (antimony [Sb], cobalt [Co], cesium [Cs], copper [Cu],
      lead [Pb], molybdenum [Mo], rubidium [Rb], selenium [Se], strontium [Sr],
      titanium [Ti], zinc [Zn]) were detected in all samples. Season of birth was the
      strongest predictor of metals in cord blood across analyses. Infants born in the
      spring had 0.1-0.2 MUg L-1 higher logAs and logCo in their cord blood (beta
      [95%CI] = 0.22 [0.01,0.42], p = 0.04; 0.11 [0.01,0.22], p = 0.04), while infants
      born in the summer had higher Sb, logB, logHg, and logZn (beta [95%CI] = 0.74
      [0.24,1.24], p = 0.004; 0.11 [0.00,0.21], p = 0.04; 0.29 [0.08,0.49], p = 0.007;
      0.18 [0.06,0.31], p = 0.005), compared to those born in fall/winter. Prenatal
      heavy metal exposure and/or trace metal deficiencies are global concerns because
      of increasing awareness of downstream developmental effects.

PMID- 30208544
TI  - Performance of the nitrogen removal, bioactivity and microbial community
      responded to elevated norfloxacin antibiotic in an Anammox biofilm system.
AB  - Antibiotic pollution in nitrogen contained wastewater is an urgent issue. In this
      study, the nitrogen removal, biofilm property and microbial community of Anammox
      system were investigated with elevated norfloxacin (NOR) feeding. Batch
      experiments were carried out to detect the specific anammox activity (SAA) in
      each phase. Anammox system could resist NOR in 0.001-50 mg L-1, in which the
      nitrogen removal was firstly limited to 0.220 from the initial 0.345 by NOR
      suppression and then regained to 0.354 kg m-3 d-1 after acclimatization. SAA
      decreased to 7.56 from the initial 10.84 and then climbed up to 11.01 mg g-1 SS,
      while the relative abundance of Candidatus Kuenenia decreased to 11.33% and then
      picked up to 25.28% from the initial 20.74%. The suppression threshold on Anammox
      was calculated as 50-100 mg L-1 NOR, the NRR, SAA and Candidatus Kuenenia
      abundance all recovered to almost the initial level when NOR feeding was
      terminated.

PMID- 30208545
TI  - A Bayesian assessment of polychlorinated biphenyl contamination of fish
      communities in the Laurentian Great Lakes.
AB  - Polychlorinated biphenyl (PCB) contamination has historically posed constraints
      on the recreational and commercial fishing industry in the Great Lakes. Empirical
      evidence suggests that PCB contamination represents a greater health risk from
      fish consumption than other legacy contaminants. The present study attempts a
      rigorous assessment of the spatio-temporal PCB trends in multiple species across
      the Canadian waters of the Great Lakes. We applied a Bayesian modelling
      framework, whereby we initially used dynamic linear models to delineate PCB
      levels and rates of change, while accounting for the role of fish length and
      lipid content as covariates. We then implemented Bayesian hierarchical modelling
      to evaluate the temporal PCB trends during the dreissenid pre- and post-invasion
      periods, as well as the variability among and within the water bodies of the
      Great Lakes system. Our analysis indicates that Lake Ontario is characterized by
      the highest PCB levels among nearly all of the fish species examined.
      Historically contaminated local areas, designated as Areas of Concern, and
      embayments receiving riverine inputs displayed higher concentrations within each
      of the water bodies examined. The general temporal trend across the Great Lakes
      was that the high PCB concentrations during the early 1970s followed a declining
      trajectory throughout the late 1980s/early 1990s, likely as a result of the
      reductions in industrial emissions and other management actions. Nonetheless,
      after the late 1990s/early 2000s, our analysis provided evidence of a decline in
      the rate at which PCB concentrations in fish were dropping, accompanied by a
      gradual establishment of species-specific, steady-state concentrations, around
      which there is considerable year-to-year variability. The overall trends indicate
      that reduced contaminant emissions have brought about distinct beneficial changes
      in fish PCB concentrations, but past historical contamination along with other
      external or internal stressors (e.g., invasive species, climate change) continue
      to modulate the current levels, thereby posing potential risks to humans through
      fish consumption.

PMID- 30208546
TI  - Fractionating magnesium ion from seawater for struvite recovery using
      electrodialysis with monovalent selective membranes.
AB  - As the consumption of global phosphorus reserves accelerates, recovering
      phosphorus as struvite (MgNH4PO4.6H2O) from wastewater is an important option for
      phosphorus recycling. However, magnesium source is one of the major limiting
      factors for struvite recovery. In this work, different from previous studies
      where seawater was used directly as magnesium source in struvite precipitation,
      an electrodialysis stack equipped with monovalent selective cation-exchange
      membranes was designed to fractionate Mg2+ from seawater for struvite recovery.
      Results revealed that Mg2+ fractionation was achieved effectively. The comparison
      on applying the driving force for ionic transport showed that constant voltage
      was more preferable than constant current due to its higher Mg2+ separation
      efficiency, current efficiency and lower energy consumption. Increasing voltage
      from 7 V to 13 V would improve Mg2+ permeation ratio from 72.9% to 80.5% into the
      product stream but simultaneously increased the energy consumption from 5.40
      (kWh/kg MgCl2) to 11.69 (kWh/kg MgCl2). In addition, the investigation on the
      influence of Ca2+ co-existence and further struvite recovery experiments revealed
      that the variation of Ca2+ concentrations in seawater did not influence Mg2+
      fractionation significantly, nevertheless it might reduce struvite recovery
      efficiency through forming calcium phosphate.

PMID- 30208547
TI  - Co3O4 nanocrystals/3D nitrogen-doped graphene aerogel: A synergistic hybrid for
      peroxymonosulfate activation toward the degradation of organic pollutants.
AB  - 3D porous Co3O4/nitrogen-doped graphene aerogel (NGA) hybrid for heterogeneous
      activation of peroxymonosulfate (PMS) was prepared by feasible hydrothermal and
      freeze-drying methods. The morphology, crystal structure and chemical composition
      of the catalyst were investigated by scanning electron microscopy, X-ray
      diffractometer, X-ray photoelectron spectroscopy, Raman spectra and Fourier
      transform infrared spectroscopy. Co3O4/NGA at a high N doping level of 7.6% (in
      atomic percentage) exhibited excellent catalytic performance for acid orange 7
      (AO7) degradation, with almost complete removal within 30 min. Moderate PMS
      content, higher temperature and lower solution pH conditions would facilitate the
      decomposition of AO7. The catalyst possesses excellent long-term stability and
      recycling performance with simple separation and post-treatment approaches.
      Kinetic model was developed to simulate the transformation of main active radical
      species and the AO7 oxidation profiles, considering effects of coexisting ions
      (Cl- and HCO3-). Based on results of electron spin resonance, typical quenching
      tests and kinetic calculation, sulfate radicals play dominate role in AO7
      degradation. Co3O4 nanocrystals and the new active sites created by nitrogen
      doping into graphene honeycomb network should synergistically contribute to the
      high degradation efficiency. This work has expanded the possibility of recyclable
      catalysts design for heterogeneous activation of PMS, with a dual catalytically
      active center and desirable stability.

PMID- 30208548
TI  - Effects of acetamiprid on life cycle development of predatory mite Amblyseius
      cucumeris (Acari: Phytoseiidae) after contact exposure.
AB  - Amblyseius cucumeris (Oudemans) is a beneficial non-target arthropod (NTA) and a
      key predator of pest mites in integrated pest management (IPM) programs across
      china. The toxic effects of insecticides have been extensively reported on
      predatory mites, but few studies devoted to the toxicity of compounds to A.
      cucumeris. In this study, the effects of a single application of acetamiprid
      against the A. cucumeris were investigated in a 48-h acute and a 30-d chronic
      test. In both tests the insecticide acetamiprid was applied once. In the acute
      test, the "open glass plate method" was used, with a 48-h LC50 value of 223.6
      (149.8-336.9) mg a. i. L-1 for adult female. The LC50 was 1.49-fold the Maximum
      field recommended concentration. In the chronic test, exposure concentrations
      (1.12, 2.24, 4.47, 8.94, and 22.4 mg a. i. L-1) were designed based on a
      preliminary 48-h LC50 value for adult female. Above treatment levels of 2.24-4.47
      mg a. i. L-1 reduce the total development time, survival rates and food
      consumption of A. cucumeris in different development stages. In addition, at
      acetamiprid concentrations higher than 2.24 mg a. i. L-1 serious effect on the
      capacity of oviposition of female adults were observed. However, even the highest
      treatment level of 22.4 mg a. i. L-1 did not affect egg hatching rates of exposed
      eggs. Acetamiprid had significant adverse effects on different development life
      stages of A. cucumeris. The results provide informative data for implementing
      biological and chemical control strategies in integrated pest management of
      spider mites.

PMID- 30208549
TI  - Assessment of the oxidative and genotoxic effects of the glyphosate-based
      herbicide roundup on the freshwater shrimp, Macrobrachium nipponensis.
AB  - In the present study, an acute toxic test was performed to assess the oxidative
      stress and genotoxic effects of the herbicide on the freshwater shrimp
      Macrobrachium nipponensis. The results showed that the 48-h and 96-h LC50 values
      of Roundup to M. nipponensis were 57.684 mg/L and 11.237 mg/L, respectively. For
      further investigation, the shrimps were exposed to sublethal concentrations of
      0.35, 0.70, 1.40, 2.80 and 5.60 mg/L for 96 h. A significant decrease in total
      haemocytes count (THC) was observed at concentration of 5.60 mg/L throughout the
      experiment. The level of superoxide dismutase (SOD), catalase (CAT) and total
      antioxidant capacity (T-AOC) in all the treatments decreased in a dose- and time
      dependent manner except for the concentration group of 0.35 mg/L. The
      malondialdehyde (MDA), hydrogen peroxide (H2O2) and protein carbonyl in serum
      increased significantly at concentrations of 2.80 mg/L and 5.60 mg/L. A
      significant decrease in acetylcholinesterase (AChE) activity was observed at each
      concentration (P<0.05). In addition, the micronucleus (MN) frequency of
      haemocytes significantly increased (P<0.05) at concentrations of 1.40, 2.80 and
      5.60 mg/L, whereas the comet ratio and %DNA in the tails exhibited a clear time-
      and dose-dependent response during the exposure. The analysis of the integrated
      biomarker response (IBR) showed the induction of oxidative stress biomarkers and
      the inhibition of antioxidants, and this dose-dependent relation suggests the
      sensitivity and availability of all the biomarkers. These results revealed that
      Roundup had a prominent toxic effect on M. nipponensis based on the antioxidative
      response inhibition and genotoxicity.

PMID- 30208551
TI  - Effects of the insecticide chlorpyrifos, on hatching, mortality and morphology of
      Duttaphrynus melanostictus embryos.
AB  - In an attempt to assess the effects of chlorpyrifos [O,O-diethyl O-(3,5,6
      trichloropyridin-2-yl) phosphorothioate], the second largest selling insecticide
      in India, studies were made with reference to some non-target organisms. The
      present study was undertaken to evaluate the effects in the embryos of
      Duttaphrynus melanostictus caused by the commercial formulations of chlorpyrifos
      (Tricel, chlorpyrifos, 20% EC). The LC50 value for Duttaphrynus melanostictus
      embryos after 48 h (h) of treatment with chlorpyrifos was found to be 57.525 ppm.
      The mortality of the embryo was significantly affected by different
      concentrations of chlorpyrifos when compared with the control groups. An increase
      in concentration of chlorpyrifos resulted in the simultaneous decrease of the
      hatching percentage and an increase in the morphological abnormalities such as
      compression of the embryo, reduced body size and curling of tail.

PMID- 30208552
TI  - Effects of rhamnolipids on the removal of 2,4,2,4-tetrabrominated biphenyl ether
      (BDE-47) by Phanerochaete chrysosporium analyzed with a combined approach of
      experiments and molecular docking.
AB  - Effects of rhamnolipids on the removal of 2,4,2,4-tetrabrominated biphenyl ether
      (BDE-47) by Phanerochaete chrysosporium (P. chrysosporium) had been investigated,
      as well as the influence of carbon source (i.e. glucose). The results showed that
      the removal efficiency was over 90% in all treatments in 7 d. Rhamnolipids at low
      concentrations (0.05 and 0.1 CMC (critical micelle concentration)) could promote
      the removal of BDE-47, however, the inhibition effects occurred at high
      concentrations (0.5 and 1.0 CMC). The further study indicated that rhamnolipids
      at low concentrations not only promote the growth of mycelium, but also had
      obvious promotion on ligninolytic enzymes activity (i.e. manganese peroxidase
      (MnP), lignin peroxidase (LiP) and laccase (Lac)), especially for MnP and Lac.
      However, the opposite effect was generated at high rhamnolipids concentrations.
      Meanwhile, glucose played an active role for BDE-47 removal. For better
      understanding the degradation mechanism, the degradation product analysis and
      molecular docking had been introduced to this study. The degradation product
      analysis indicated that OH-PBDEs were the major degradation products and
      hydroxylation should be the important degradation pathway. The docking results
      showed that the ideal binding conformation occurred between ligninolytic enzymes
      and BDE-47, and hydrophobic interactions were the main interaction. Moreover,
      hydrogen bonds and hydrophobic interactions both existed in ligninolytic enzymes
      and rhamnolipids interaction. That might be the reason that rhamnolipids affected
      enzymes activity. These results indicated that P. chrysosporium might be a type
      of ideal microorganisms in the removal of BDE-47 pollution, and rhamnolipids
      could be a type of additives for better removal efficiency.

PMID- 30208550
TI  - ZrO2 nanoparticles confined in metal organic frameworks for highly effective
      adsorption of phosphate.
AB  - Highly dispersed ZrO2 particles confined in the MIL-101 (denoted as MIL
      101@Zr(DS)) with varied ZrO2 loading amounts were prepared by the double solvents
      method. For comparison, ZrO2 loaded MIL-101 samples were synthesized by the
      conventional impregnation method (denoted as MIL-101@Zr(I)) and the deposition
      method (denoted as MIL-101@Zr(D)). The characterization results indicated that
      for MIL-101@Zr(DS), ZrO2 particles were dominantly confined in MIL-101 with a
      much higher dispersion as compared with MIL-101@Zr(I) and MIL-101@Zr(D). The
      maximum phosphate adsorption capacity and ZrO2 content normalized phosphate
      adsorption capacity of the MIL-101@Zr(DS) were 21.28 mg P.g-1 and 1120.0 mg P.g
      1, respectively. Additionally, the ZrO2 content normalized phosphate adsorption
      capacity was significantly larger than that for MIL-101@Zr(I) and MIL-101@Zr(D)
      as well as the reported values for other Zr-based adsorbents. The effects of
      solution chemistry on phosphate adsorption to MIL-101@Zr(DS), MIL-101@Zr(I) and
      MIL-101@Zr(D) were also examined. Compared with MIL-101@Zr(I) and MIL-101@Zr(D),
      the adsorption of phosphate on MIL-101@Zr(DS) was less affected by the
      coexistence of anions and dissolved humic acid. Increasing pH from 3 to 12 led to
      decreased phosphate adsorption capacity of MIL-101@Zr(DS) from 10.38 mg P.g-1 to
      2.03 mg P.g-1. Accordingly, used MIL-101@Zr(DS) could be effectively regenerated
      under alkaline conditions and exhibited stable adsorption-desorption performance.

PMID- 30208553
TI  - Optimization of sensing performance in an integrated dual sensors system
      combining microbial fuel cells and upflow anaerobic sludge bed reactor.
AB  - Two bio-cathode microbial fuel cells (MFCs) with Upflow anaerobic sludge blanket
      (UASB) are integrated to construct a UASB-MFC dual sensors system, developed to
      solve the problems of low accuracy and less information about the single sensor
      system. The bio-cathode MFC is developed as the biosensor for UASB operation
      performance and online monitoring. Owing to the biosorption of anaerobic
      microbes, the MFC in the suspended layer is more suitable for effluent chemical
      oxygen demand (COD) real-time monitoring, and the MFC in the sludge layer is more
      suitable for total volatile fatty acid (TVFA) real-time monitoring.
      Electrochemical analysis discovers that the lower electron transfer resistance
      determines the higher sensitivity of MFC in the suspended layer. The difference
      in species abundance indicates that TVFA has a stronger inhibitory effect on MFC
      in the sludge layer. The novel UASB-MFC dual sensors system shows promising
      potential for COD and TVFA simultaneous online monitoring, which can enhance the
      reliability of anaerobic reaction.

PMID- 30208554
TI  - Comparative evaluation of influence of aging, soil properties and structural
      characteristics on bioaccessibility of polychlorinated biphenyls in soil.
AB  - Though bioaccessibility commonly recognized as a guideline for risk assessment is
      closely related with pollution occurrence and chemical species of compounds, the
      mechanistic links are barely evaluated particularly for widespread
      polychlorinated biphenyls (PCBs) in soil. With the biomimetic extraction of
      hydroxypropyl-beta-cyclodextrin (beta-HPCD), the temporal and spatial influences
      of soil properties, aging and structural characteristics, e.g. polarity of PCB
      congeners on bioaccessibility were investigated for PCBs. Sensitive variation of
      bioaccessibility with aging, soil organic matter (SOM), particle size and soil
      moisture were clearly evidenced for different PCB congeners. Due to aging, the
      bioaccessibility decreased in the long term after stabilization for 36 h. In
      concert with the first-order kinetics, the decay rates of bioaccessibility were
      shown with congener-specificity and were well correlated with dipoles of PCBs.
      The increment of SOM diminished the bioaccessibility for the strengthened
      adsorption while the increased particle size and soil moisture elevated it
      possibly due to the less adsorption on soil particles and more accommodation of
      PCBs in soil pore water. Except the positive correlations with particle size,
      soil moisture and dipole moment, the greater dependency on aging and SOM was
      highlighted for bioaccessibility by partial least squares (PLS) analysis. The
      mutual relationship with influential factors was quantitatively formulated for
      accelerative prediction of bioaccessibility, and the comparative evaluation and
      detailed insights into the mechanistic links would thus help enhance the precise
      determination of bioaccessibility and risk assessment of PCBs in soil.

PMID- 30208555
TI  - Life-cycle exposure to cadmium induced compensatory responses towards oxidative
      stress in the liver of female zebrafish.
AB  - The current study examined effects of waterborne cadmium (Cd) at environmental
      relevant concentrations (0, 2.5 and 5 MUg/L) on growth, survival, histology,
      ultrastructure, metal homeostasis, and antioxidant responses in female zebrafish
      from embryos to sexually maturity for 15 weeks. Growth and survival rate were not
      significantly affected by Cd exposure. There were no significant changes in
      ultrastructure of cellular organelles, reactive oxygen species (ROS) levels,
      lipid peroxidation (LPO) in liver. However, Cd exposure increased Cd and lipid
      accumulation, reduced contents of zinc, copper and reduced glutathione (GSH), and
      down-regulated activity of copper/zinc-superoxide dismutase (Cu/Zn-SOD) in liver
      of zebrafish. Contrarily, the mRNA and activity levels of catalase (CAT), the
      mRNA levels of Cu/Zn-SOD, and the mRNA and protein levels of metallothioneins
      (MTs) were up-regulated. The transcriptional regulation of Cu and Zn transporters
      might be a vital mechanism by which fish slow the Zn and Cu uptake. Taken
      together, our data demonstrated that long-term and low-dose Cd induced adaptive
      responses with interlinked compensatory mechanism, which may protect fish against
      oxidative stress.

PMID- 30208556
TI  - The pyrethroid lambda-cyhalothrin induces biochemical, genotoxic, and
      physiological alterations in the teleost Prochilodus lineatus.
AB  - The lambda-cyhalothrin (CL) is a globally used pyrethroid insecticide that has
      been detected in different water bodies worldwide. However, studies on the
      effects of CL on freshwater fishes are still incipient. In this context, we
      evaluated the acute effects of a commercial formulation containing CL (Karate
      Zeon(r) CS 50) in juveniles of the teleost Prochilodus lineatus exposed for 96 h
      to four concentrations of the active ingredient (5, 50, 250 and 500 ng.L-1).
      Biochemical, physiological, and genotoxic biomarkers were evaluated in different
      organs of the fish. Exposure to CL induced significant changes in the enzymatic
      profiles of P. lineatus, with specific alterations in biotransformation enzymes
      and antioxidant defence in different tissues. Lipid peroxidation was observed in
      fish gills and kidney. Increases in esterases were observed in the liver of fish
      exposed to all CL concentrations evaluated, whereas acetylcholinesterase activity
      decreased in the muscles of fish at all concentrations. CL also promoted
      osmoregulatory disorders, with decreases in calcium and magnesium gill ATPases,
      with consequent hypocalcaemia, in addition an increase in sodium-potassium ATPase
      activity was observed in the gills of fish exposed to the highest CL
      concentration, probably in order to compensate a reduction in plasma sodium.
      Besides, increases in DNA damage were observed in the erythrocytes of fish
      exposed to all CL concentrations. Thus, despite the low CL concentrations and the
      short exposure time, this pyrethroid caused hematological adjustments, oxidative
      stress, osmoregulatory disorders, and DNA damage in P. lineatus, showing that the
      species is highly sensitive to the deleterious effects of CL.

PMID- 30208557
TI  - In situ phytoremediation of dyes from textile wastewater using garden ornamental
      plants, effect on soil quality and plant growth.
AB  - In situ phytoremediation of dyes from textile wastewater was carried out in a
      high rate transpiration system ridges (91.4 m * 1.0 m) cultivated independently
      with Tagetes patula, Aster amellus, Portulaca grandiflora and Gaillardia
      grandiflora which reduced American Dye Manufacturers Institute color value by 59,
      50, 46 and 73%, respectively within 30 d compared to dye accumulated in unplanted
      ridges. Significant increase in microbial count and electric conductivity of soil
      was observed during phytoremediation. Reduction in the contents of macro (N, P, K
      and C), micro (B, Cu, Fe and Mn) elements and heavy metals (Cd, As, Pb and Cr)
      was observed in the soil from planted ridges due to phyto-treatment. Root tissues
      of these plants showed significant increase in the specific activities of oxido
      reductive enzymes such as lignin peroxidase, laccase, veratryl alcohol oxidase,
      tyrosinase and azo reductase during decolorization of textile dyes from soil.
      Anatomical studies of plants roots revealed the occurrence of textile dyes in
      tissues and subsequent degradation. A minor decrease in plant growth was also
      observed. Overall surveillance suggests that the use of garden ornamental plants
      on the ridges of constructed wetland for the treatment of dyes from wastewater
      along with the consortia of soil microbial flora is a wise and aesthetically
      pleasant strategy.

PMID- 30208558
TI  - Enhanced remedial reagents delivery in unsaturated anisotropic soils using
      surfactant foam.
AB  - Homogeneous delivery of solution of oxidant in unsaturated soils is limited by
      soil anisotropy and gravity. An innovative injection strategy using foam was
      developed to improve in situ delivery. Primary foam injection before oxidant
      solution enhanced both the lateral and uniform delivery of reactant in isotropic
      and anisotropic (permeability, contamination) soils. The oxidant spread
      isotropically through the foam water network. This sequential injection heavily
      improved the delivery radius of influence (ROI), while limiting contact between
      surfactant and solution of oxidant in order to preserve the selective oxidation
      of petroleum hydrocarbons contaminant (TPH). Prior foam injection allowed uniform
      delivery of the solution of oxidant across the region occupied by the foam,
      regardless of the soil permeability contrast (1:18), whereas poor ROI were
      observed for the direct injection of oxidant. Experiments in contamination
      contrasted soils showed that foam was able to propagate in highly TPH
      contaminated soils (max 60% velocity reduction for 22 g.kgdry soil-1). As for
      permeability contrast, foam is expected to enhance reagents delivery in such
      contexts. This novel strategy was proven to be efficient, even for complex
      anisotropic conditions, and should allow to cut field costs and uncertainties
      associated to poor reagents delivery.

PMID- 30208559
TI  - Arsenic accumulation in paddy plants at different phases of pre-monsoon
      cultivation.
AB  - Geogenic arsenic (As) contamination in Bengal Delta Plain is a growing
      environmental and research concern. Cultivation of staple crops like paddy on
      these contaminated fields is one of the major routes for human dietary exposure.
      The present study investigates changes of arsenic concentrations in paddy plant
      parts, root soil and surface soil throughout the various phases of pre-monsoon
      (boro) cultivation. Arsenic uptake property of paddy plants collected from 10
      fields was found to be dependent on the variety of paddy plant (like Minikit,
      Jaya) rather than arsenic levels in groundwater (0.074-0.301 mg/l) or soil (25.3
      60 mg/kg). Arsenic is translocated from root to aerial parts in descending order.
      Leaf, stem, root, root soil and surface soil showed a similar trend in their
      change of arsenic concentration throughout the cultivation period. Arsenic
      concentration was highest in vegetative phase; sharply declined in reproductive
      phase; followed by moderate increase in ripening phase. The young root tissues in
      vegetative (primary) phase could uptake arsenic at a much faster rate than the
      older tissues in later phases. With the growth of the plant, higher
      concentrations of iron in root soil in the reproductive phase confirmed the
      formation of iron plaques on the surface of the root, which sequester arsenic and
      prevented its uptake by plants. Finally, co-precipitation of arsenic with iron
      released from crystallized iron plaques results in loosening of the iron plaques
      from root surface. Thus, soil arsenic concentration increases in the final phase
      of cultivation which in turn contributes to increased concentration in plant
      parts.

PMID- 30208560
TI  - Impaired lipid and glucose homeostasis in male mice offspring after combined
      exposure to low-dose bisphenol A and arsenic during the second half of gestation.
AB  - In this study, we used a 1H NMR based metabolomics strategy combined with gene
      expression analysis to determine the combined effects of gestational exposure of
      mice to BPA (10 MUg/kg body weight by subcutaneous injection) and arsenic (10 ppb
      sodium arsenite in drinking water). Results showed that exposure to either BPA
      or, arsenic or their combination induced age-dependent metabolic disruptions in
      male mice offspring, and the combined exposure could exacerbate the metabolic
      changes induced by either BPA or arsenic alone. Moreover, this combined exposure
      influenced both glucose tolerance and insulin tolerance in mice, along with
      changing the expression of genes involved in lipid and glucose homeostasis.
      Specifically, the combined exposure to BPA and arsenic promoted the uptake of
      glucose and fatty acid from serum to liver, and genes involved in glycogenesis,
      glucogenesis, and fatty acid oxidation were activated in the liver in the
      combined exposure group. Taken together, these experimental results highlight the
      importance of considering the combined toxicity of environmental pollutants at
      levels relevant to human exposure, especially during the early life stages of
      mammals.

PMID- 30208561
TI  - FK506 Attenuates the MRP1-Mediated Chemoresistant Phenotype in Glioblastoma Stem
      Like Cells.
AB  - Poor response to current treatments for glioblastoma has been attributed to the
      presence of glioblastoma stem-like cells (GSCs). GSCs are able to expel antitumor
      drugs to the extracellular medium using the multidrug resistance-associated
      protein 1 (MRP1) transporter. Tacrolimus (FK506) has been identified as an MRP1
      regulator in differentiated glioblastoma (GBM) cells (non-GSCs); however, the
      effect of FK506 on GSCs is currently unknown. The objective of the following
      research is to evaluate the effect of FK506 on the MRP1-related chemo-resistant
      phenotype of GSCs. For this, U87MG and C6 glioma cell lines were used to generate
      non-GSCs and GSCs. mRNA and MRP1-positive cells were evaluated by RT-qPCR and
      flow cytometry, respectively. A Carboxyfluorescein Diacetate (CFDA)-retention
      assay was performed to evaluate the MRP1 activity. Apoptosis and MTT assays were
      employed to evaluate the cytotoxic effects of FK506 plus Vincristine (MRP1
      substrate). GSC-derived subcutaneous tumors were generated to evaluate the in
      vivo effect of FK506/Vincristine treatment. No differences in transcript levels
      and positive cells for MRP1 were observed in FK506-treated cells. Lesser cell
      viability, increased apoptosis, and CFDA-retention in the FK506/Vincristine
      treated cells were observed. In vivo, the FK506/Vincristine treatment decreased
      the tumor size as well as ki67, Glial Fibrillary Acidic Protein (GFAP), and
      nestin expression. We conclude that FK506 confers a chemo-sensitive phenotype to
      MRP1-drug substrate in GSCs.

PMID- 30208563
TI  - Comparison of Physicochemical Properties of Starches from Flesh and Peel of Green
      Banana Fruit.
AB  - Green banana fruit is an important starch resource that consists of flesh and
      peel. The physicochemical properties of flesh starch have been widely studied;
      however, those of peel starch have hardly been studied, leading to the waste of
      peel. In this study, the physicochemical properties of the starches from the
      flesh and peel of green banana fruit were investigated and compared. The dry
      flesh and peel had 69.5% and 22.6% starch content, respectively. The starch had
      oval and irregular granules with eccentric hila. Their starches had similar
      bimodal size distribution; the volume-weighted mean diameter was approximate 17
      MUm, and the peel starch had a slightly smaller granule size than the flesh
      starch. The maximum absorption wavelength was higher in peel starch than in flesh
      starch. The apparent amylose content of flesh and peel starch was 21.3% and
      25.7%, respectively. The flesh and peel starches both exhibited B-type
      crystalline structures and had similar relative crystallinity, short-range
      ordered degrees, and lamellar structures. The swelling power was similar between
      flesh and peel starches, but the water solubility was higher in peel starch than
      in flesh starch at 95  degrees C. The peel starch had a higher gelatinization
      temperature than flesh starch, but their gelatinization temperature range and
      enthalpy were similar. Both flesh and peel starches showed a diphasic hydrolysis
      dynamic, but peel starch had higher resistance to porcine pancreatic alpha
      amylase hydrolysis than flesh starch. The contents of rapidly digestible starch,
      slowly digestible starch, and the resistant starch of flesh and peel were 1.7%,
      4.3%, 94.1% and 1.4%, 3.4%, 95.2%, respectively, for native starch, and 73.0%,
      5.1%, 21.9%, and 72.3%, 4.5%, 23.2%, respectively, for gelatinized starch.

PMID- 30208564
TI  - Fibrosis Staging Using Direct Serum Biomarkers is Influenced by Hepatitis
      Activity Grading in Hepatitis C Virus Infection.
AB  - BACKGROUND: Chronic liver diseases (CLDs) generally progress from inflammation to
      fibrosis and finally to carcinogenesis. Staging of liver fibrosis progression is
      inevitable for the management of CLD patients. The purpose of this study was to
      compare the diagnostic abilities of Wisteria floribunda agglutinin-positive Mac-2
      binding protein (WFA-M2BP), Enhanced liver fibrosis (ELF) score, Fibrosis-4
      index, and AST to platelet ratio index (APRI) based on histopathological analysis
      of liver biopsy samples, from patients with positive Hepatitis C Virus (HCV)
      infection. METHODS: Japanese patients with HCV infection who underwent liver
      biopsy examinations were enrolled in this study. WFA-M2BP levels and ELF scores
      were calculated using preserved serum samples. The fibrosis staging and activity
      grading were assessed using a modified METAVIR score. RESULTS: A total of 122
      patients were enrolled; the cohort included 27 patients with stage 1, 66 with
      stage 2, 20 with stage 3, and nine with stage 4 fibrosis. All four biomarkers
      distinguished stage 3 and stage 2 fibrosis. ROC curves revealed that all four
      fibrosis biomarkers presented AUC values greater than 0.8. Each of the four
      biomarkers in stage 2 was significantly different between the activity grade 1
      and 2 groups. CONCLUSION: Fib-4 index and APRI were comparable with WFA-M2BP and
      ELF score in the diagnosis of advanced liver fibrosis in Japanese patients with
      HCV infection. All four biomarkers of liver fibrosis were influenced by
      histopathological activity grading, which implies that liver biopsy should be the
      gold standard to evaluate liver fibrosis staging even though several noninvasive
      biomarkers have been investigated well.

PMID- 30208565
TI  - Risk Assessment of Two Insecticides on Encarsia formosa, Parasitoid of Whitefly
      Bemisia tabaci.
AB  - The assessment of acute toxicity to insect natural enemies is very important for
      insecticide selection used within integrated pest management (IPM). The acute
      toxicity of abamectin and imidacloprid against Encarsia formosa, a parasitoid of
      Bemisia tabaci, was investigated. Abamectin had a high toxicity risk to E.
      formosa, while imidacloprid showed a medium toxicity risk. When treated with the
      lethal concentration 30 (LC30) of abamectin, the dwelling time of E. formosa in
      B. tabaci infested-plant-area (IPA) was significantly lower than in non-infested
      plant areas (non-IPA). In addition, the frequency of E. formosa entering into the
      two areas was not significantly different in the LC10 and LC30 treatments. Within
      the IPA, LC10, and LC30 treatments decreased the dwelling time and entering
      frequency of parasitoid significantly. For imidacloprid treatments, E. formosa
      stayed a longer time in the non-IPA than in the IPA when treated with LC30. The
      frequency of E. formosa entering into the two areas was only slightly different
      in the LC1, LC10, and LC30 treatments. Within the IPA, LC10 and LC30 treatments
      were significantly decreased in the dwelling time and the entering frequency of
      E. formosa. The results indicate that abamectin and imidacloprid have high or
      medium acute toxicity against E. formosa and a negative sublethal effect on its
      searching behaviour.

PMID- 30208562
TI  - Application of Plant Viruses as a Biotemplate for Nanomaterial Fabrication.
AB  - Viruses are widely used to fabricate nanomaterials in the field of
      nanotechnology. Plant viruses are of great interest to the nanotechnology field
      because of their symmetry, polyvalency, homogeneous size distribution, and
      ability to self-assemble. This homogeneity can be used to obtain the high
      uniformity of the templated material and its related properties. In this paper,
      the variety of nanomaterials generated in rod-like and spherical plant viruses is
      highlighted for the cowpea chlorotic mottle virus (CCMV), cowpea mosaic virus
      (CPMV), brome mosaic virus (BMV), and tobacco mosaic virus (TMV). Their recent
      studies on developing nanomaterials in a wide range of applications from
      biomedicine and catalysts to biosensors are reviewed.

PMID- 30208566
TI  - CaSK23, a Putative GSK3/SHAGGY-Like Kinase of Capsicum annuum, Acts as a Negative
      Regulator of Pepper's Response to Ralstonia solanacearum Attack.
AB  - GSK3-like kinases have been mainly implicated in the brassinosteroids (BR)
      pathway and, therefore, in plant growth, development, and responses to abiotic
      stresses; however, their roles in plant immunity remain poorly understood.
      Herein, we present evidence that CaSK23, a putative GSK3/SHAGGY-like kinase in
      pepper, acts as a negative regulator in pepper's response to Ralstonia
      solanacearum (R. solanacearum) inoculation (RSI). Data from quantitative RT-PCR
      (qRT-PCR) showed that the constitutively-expressed CaSK23 in pepper leaves was
      down-regulated by RSI, as well as by exogenously-applied salicylic acid (SA) or
      methyl jasomonate (MeJA). Silencing of CaSK23 by virus-induced gene silencing
      (VIGS) decreased the susceptibility of pepper plants to RSI, coupled with up
      regulation of the tested genes encoding SA-, JA-, and ethylene (ET)-dependent
      pathogenesis-related (PR) proteins. In contrast, ectopic overexpression (OE) of
      CaSK23 conferred a compromised resistance of tobacco plants to RSI, accompanied
      by down-regulation of the tested immunity-associated SA-, JA-, and ET-dependent
      PR genes. In addition, transient overexpression of CaSK23 in pepper plants
      consistently led to down-regulation of the tested SA-, JA-, and ET-dependent PR
      genes. We speculate that CaSK23 acts as a negative regulator in pepper immunity
      and its constitutive expression represses pepper immunity in the absence of
      pathogens. On the other hand, its decreased expression derepresses immunity when
      pepper plants are attacked by pathogens.

PMID- 30208567
TI  - Application and Validation of Activity Monitors' Epoch Lengths and Placement
      Sites for Physical Activity Assessment in Exergaming.
AB  - We assessed the agreement of two ActiGraph activity monitors (wGT3X vs. GT9X)
      placed at the hip and the wrist and determined an appropriate epoch length for
      physical activity levels in an exergaming setting. Forty-seven young adults
      played a 30-min exergame while wearing wGT3X and GT9X on both hip and wrist
      placement sites and a heart rate sensor below the chest. Intraclass correlation
      coefficient indicated that intermonitor agreement in steps and activity counts
      was excellent on the hip and good on the wrist. Bland-Altman plots indicated good
      intermonitor agreement in the steps and activity counts on both placement sites
      but a significant intermonitor difference was detected in steps on the wrist.
      Time spent in sedentary and physical activity intensity levels varied across six
      epoch lengths and depended on the placement sites, whereas time spent from a 1-s
      epoch of the hip-worn monitors most accurately matched the relative exercise
      intensity by heart rate. Hip placement site was associated with better step
      counting accuracy for both activity monitors and more valid estimation of
      physical activity levels. A 1-s epoch was the most appropriate epoch length to
      detect short bursts of intense physical activity and may be the best choice for
      data processing and analysis in exergaming studies examining intermittent
      physical activities.

PMID- 30208568
TI  - Weight Loss Maintenance: Have We Missed the Brain?
AB  - Even though obese individuals often succeed with weight loss, long-term weight
      loss maintenance remains elusive. Dietary, lifestyle and psychosocial correlates
      of weight loss maintenance have been researched, yet the nature of maintenance is
      still poorly understood. Studying the neural processing of weight loss
      maintainers may provide a much-needed insight towards sustained obesity
      management. In this narrative review, we evaluate and critically discuss
      available evidence regarding the food-related neural responses of weight loss
      maintainers, as opposed to those of obese or lean persons. While research is
      still ongoing, available data indicate that following weight loss, maintainers
      exhibit persistent reward related feeling over food, similar to that of obese
      persons. However, unlike in obese persons, in maintainers, reward-related brain
      activity appears to be counteracted by subsequently heightened inhibition. These
      findings suggest that post-dieting, maintainers acquire a certain level of
      cognitive control which possibly protects them from weight regaining. The
      prefrontal cortex, as well as the limbic system, encompass key regions of
      interest for weight loss maintenance, and their contributions to long term
      successful weight loss should be further explored. Future possibilities and
      supportive theories are discussed.

PMID- 30208571
TI  - Carbon Nanomaterials Based Smart Fabrics with Selectable Characteristics for In
      Line Monitoring of High-Performance Composites.
AB  - Carbon nanomaterials have gradually demonstrated their superiority for in-line
      process monitoring of high-performance composites. To explore the advantages of
      structures, properties, as well as sensing mechanisms, three types of carbon
      nanomaterials-based fiber sensors, namely, carbon nanotube-coated fibers, reduced
      graphene oxide-coated fibers, and carbon fibers, were produced and used as key
      sensing elements embedded in fabrics for monitoring the manufacturing process of
      fiber-reinforced polymeric composites. Detailed microstructural characterizations
      were performed through SEM and Raman analyses. The resistance change of the smart
      fabric was monitored in the real-time process of composite manufacturing. By
      systematically analyzing the piezoresistive performance, a three-stage sensing
      behavior has been achieved for registering resin infiltration, gelation, cross
      linking, and post-curing. In the first stage, the incorporation of resin expands
      the packing structure of various sensing media and introduces different levels of
      increases in the resistance. In the second stage, the concomitant resin shrinkage
      dominates the resistance attenuation after reaching the maximum level. In the
      last stage, the diminished shrinkage effect competes with the disruption of the
      conducting network, resulting in continuous rising or depressing of the
      resistance.

PMID- 30208570
TI  - Risk and Predisposing Factors for Suicide Attempts in Patients with Migraine and
      Status Migrainosus: A Nationwide Population-Based Study.
AB  - OBJECTIVE: To investigate the risk and risk factors for suicide attempt by
      patients with regular migraines (RM) and status migrainosus (SM) in Taiwan.
      METHODS: We analyzed a subset of the National Health Insurance Research Database
      of Taiwan and enrolled patients (>=20 years old) who had ever received a
      diagnosis of RM or SM between 2000 and 2012 in the RM and SM cohort. The SM
      cohort included 13,605 patients, the RM cohort had 21,485 patients, and the
      comparison cohort contained approximately four times that many patients. We
      calculated the adjusted hazard ratios and 95% confidence intervals (CI) for
      suicide attempts after adjusting for age, sex, monthly income, urbanization
      level, occupation, and comorbidities. RESULTS: The SM cohort had a 1.81-fold risk
      of attempting suicide (95% CI = 1.14-2.89) compared to the comparison cohort.
      Other factors that predispose patients with SM to attempt suicide include the
      following: female sex, relatively young age (<50 years old), and low monthly
      income (<15,000 New Taiwan Dollars, approximately equivalent to 495 US Dollars).
      Additionally, the risk of attempting suicide only increased in patients who had
      been diagnosed with SM for longer than five years. CONCLUSION: SM is associated
      with a higher risk for suicide attempt in migraineurs in Taiwan. This finding is
      important to clinicians and government officials seeking to prevent patients from
      attempting suicide in Taiwan and other similar East Asian countries.

PMID- 30208569
TI  - The Cutaneous Microbiome and Wounds: New Molecular Targets to Promote Wound
      Healing.
AB  - The ecological community of microorganisms in/on humans, termed the microbiome,
      is vital for sustaining homeostasis. While culture-independent techniques have
      revealed the role of the gut microbiome in human health and disease, the role of
      the cutaneous microbiome in wound healing is less defined. Skin commensals are
      essential in the maintenance of the epithelial barrier function, regulation of
      the host immune system, and protection from invading pathogenic microorganisms.
      In this review, we summarize the literature derived from pre-clinical and
      clinical studies on how changes in the microbiome of various acute and chronic
      skin wounds impact wound healing tissue regeneration. Furthermore, we review the
      mechanistic insights garnered from model wound healing systems. Finally, in the
      face of growing concern about antibiotic-resistance, we will discuss alternative
      strategies for the treatment of infected wounds to improve wound healing and
      outcomes. Taken together, it has become apparent that commensals, symbionts, and
      pathogens on human skin have an intimate role in the inflammatory response that
      highlights several potential strategies to treat infected, non-healing wounds.
      Despite these promising results, there are some contradictory and controversial
      findings from existing studies and more research is needed to define the role of
      the human skin microbiome in acute and chronic wound healing.

PMID- 30208573
TI  - Fringing Electric Field Sensors for Anti-Attack at System-Level Protection.
AB  - Information system security has been in the spotlight of individuals and
      governments in recent years. Integrated Circuits (ICs) function as the basic
      element of communication and information spreading, therefore they have become an
      important target for attackers. From this perspective, system-level protection to
      keep chips from being attacked is of vital importance. This paper proposes a
      novel method based on a fringing electric field (FEF) sensor to detect whether
      chips are dismantled from a printed circuit board (PCB) as system-level
      protection. The proposed method overcomes the shortcomings of existing techniques
      that can be only used in specific fields. After detecting a chip being dismantled
      from PCB, some protective measures like deleting key data can be implemented to
      be against attacking. Fringing electric field sensors are analyzed through
      simulation. By optimizing sensor's patterns, areas and geometrical parameters,
      the methods that maximize sensitivity of fringing electric field sensors are put
      forward and illustrated. The simulation is also reproduced by an experiment to
      ensure that the method is feasible and reliable. The results of experiments are
      inspiring in that they prove that the sensor can work well for protection of
      chips and has the advantage of universal applicability, low cost and high
      reliability.

PMID- 30208572
TI  - Microbial Degradation of Pesticide Residues and an Emphasis on the Degradation of
      Cypermethrin and 3-phenoxy Benzoic Acid: A Review.
AB  - Nowadays, pesticides are widely used in preventing and controlling the diseases
      and pests of crop, but at the same time pesticide residues have brought serious
      harm to human's health and the environment. It is an important subject to study
      microbial degradation of pesticides in soil environment in the field of
      internationally environmental restoration science and technology. This paper
      summarized the microbial species in the environment, the study of herbicide and
      pesticides degrading bacteria and the mechanism and application of pesticide
      microbial degrading bacteria. Cypermethrin and other pyrethroid pesticides were
      used widely currently, while they were difficult to be degraded in the natural
      conditions, and an intermediate metabolite, 3-phenoxy benzoic acid would be
      produced in the degradation process, causing the secondary pollution of
      agricultural products and a series of problems. Taking it above as an example,
      the paper paid attention to the degradation process of microorganism under
      natural conditions and factors affecting the microbial degradation of pesticide.
      In addition, the developed trend of the research on microbial degradation of
      pesticide and some obvious problems that need further solution were put forward.

PMID- 30208575
TI  - Association between Subjective Indicators of Recovery Status and Heart Rate
      Variability among Divison-1 Sprint-Swimmers.
AB  - Heart rate variability (HRV) is a physiological marker of training adaptation
      among athletes. However, HRV interpretation is challenging when assessed in
      isolation due to its sensitivity to various training and non-training-related
      factors. The purpose of this study was to determine the association between
      athlete-self report measures of recovery (ASRM) and HRV throughout a preparatory
      training period. Ultra-short natural logarithm of the root mean square of
      successive differences (LnRMSSD) and subjective ratings of sleep quality,
      fatigue, muscle soreness, stress and mood were acquired daily for 4 weeks among
      Division-1 sprint-swimmers (n = 17 males). ASRM were converted to z-scores and
      classified as average (z-score -0.5-0.5), better than average (z-score > 0.5) or
      worse than average (z-score < -0.5). Linear mixed models were used to evaluate
      differences in LnRMSSD based on ASRM classifications. LnRMSSD was higher (p <
      0.05) when perceived sleep quality, fatigue, stress and mood were better than
      average versus worse than average. Within-subject correlations revealed that 15
      of 17 subjects demonstrated at least one relationship (p < 0.05) between LnRMSSD
      and ASRM variables. Changes in HRV may be the result of non-training related
      factors and thus practitioners are encouraged to include subjective measures to
      facilitate targeted interventions to support training adaptations.

PMID- 30208574
TI  - Aflibercept Nanoformulation Inhibits VEGF Expression in Ocular In Vitro Model: A
      Preliminary Report.
AB  - Age-related macular degeneration (AMD) is one of the leading causes of blindness
      in the United States, affecting approximately 11 million patients. AMD is caused
      primarily by an upregulation of vascular endothelial growth factor (VEGF). In
      recent years, aflibercept injections have been used to combat VEGF. However, this
      treatment requires frequent intravitreal injections, leading to low patient
      compliance and several adverse side effects including scarring, increased
      intraocular pressure, and retinal detachment. Polymeric nanoparticles have
      demonstrated the ability to deliver a sustained release of drug, thereby reducing
      the necessary injection frequency. Aflibercept (AFL) was encapsulated in poly
      lactic-co-glycolic acid (PLGA) nanoparticles (NPs) via double emulsion diffusion.
      Scanning electron microscopy showed the NPs were spherical and dynamic light
      scattering demonstrated that they were uniformly distributed (PDI < 1). The
      encapsulation efficiency and drug loading were 75.76% and 7.76% respectively. In
      vitro release studies showed a sustained release of drug; 75% of drug was
      released by the NPs in seven days compared to the full payload released in 24 h
      by the AFL solution. Future ocular in vivo studies are needed to confirm the
      biological effects of the NPs. Preliminary studies of the proposed aflibercept
      NPs demonstrated high encapsulation efficiency, a sustained drug release profile,
      and ideal physical characteristics for AMD treatment. This drug delivery system
      is an excellent candidate for further characterization using an ocular
      neovascularization in vivo model.

PMID- 30208577
TI  - Bacillamidins A-G from a Marine-Derived Bacillus pumilus.
AB  - Seven long-chain amides, including five previously undescribed bacillamidins A-E
      (1-5) and two previously reported synthetic analogs, bacillamidins F (6) and G
      (7), were isolated from extracts of the marine-derived Bacillus pumilus strain
      RJA1515. The structures of the new compounds were established by extensive
      analysis of 1D and 2D nuclear magnetic resonance (NMR) data as well as high
      resolution mass spectrometry (HRMS), and the absolute configurations of the
      stereogenic carbons of 1-4 were established by comparison of the calculated and
      the experimental electronic circular dichroism (ECD) spectra. The cytotoxic and
      antimicrobial activities of 1-7 were evaluated.

PMID- 30208576
TI  - Inhibition of Prostate Cancer DU-145 Cells Proliferation by Anthopleura anjunae
      Oligopeptide (YVPGP) via PI3K/AKT/mTOR Signaling Pathway.
AB  - We investigated the antitumor mechanism of Anthopleura anjunae oligopeptide (AAP
      H, YVPGP) in prostate cancer DU-145 cells in vitro and in vivo. Results indicated
      that AAP-H was nontoxic and exhibited antitumor activities. Cell cycle analysis
      indicated that AAP-H may arrest DU-145 cells in the S phase. The role of the
      phosphatidylinositol 3-kinase/protein kinase B/mammalian rapamycin target protein
      (PI3K/AKT/mTOR) signaling pathway in the antitumor mechanism of APP-H was
      investigated. Results showed that AAP-H treatment led to dose-dependent reduction
      in the levels of p-AKT (Ser473), p-PI3K (p85), and p-mTOR (Ser2448), whereas t
      AKT and t-PI3K levels remained unaltered compared to the untreated DU-145 cells.
      Inhibition of PI3K/AKT/mTOR signaling pathway in the DU-145 cells by employing
      inhibitor LY294002 (10 MUM) or rapamycin (20 nM) effectively attenuated AAP-H
      induced phosphorylation of AKT and mTOR. At the same time, inhibitor addition
      further elevated AAP-H-induced cleaved-caspase-3 levels. Furthermore, the effect
      of AAP-H on tumor growth and the role of the PI3K/AKT/mTOR signaling pathway in
      nude mouse model were also investigated. Immunohistochemical analysis showed that
      activated AKT, PI3K, and mTOR levels were reduced in DU-145 xenografts. Western
      blotting showed that AAP-H treatment resulted in dose-dependent reduction in p
      AKT (Ser473), p-PI3K (p85), and p-mTOR (Ser2448) levels, whereas t-AKT and t-PI3K
      levels remained unaltered. Similarly, Bcl-xL levels decreased, whereas that of
      Bax increased after AAP-H treatment. AAP-H also increased initiator (caspase 8
      and 9) and executor caspase (caspase 3 and 7) levels. Therefore, the antitumor
      mechanism of APP-H on DU-145 cells may involve regulation of the PI3K/AKT/mTOR
      signaling pathway, which eventually promotes apoptosis via mitochondrial and
      death receptor pathways. Thus, the hydrophobic oligopeptide (YVPGP) can be
      developed as an adjuvant for the prevention or treatment of prostate cancer in
      the future.

PMID- 30208578
TI  - A Brief Questionnaire to Assess Post-Exertional Malaise.
AB  - Post-exertional malaise (PEM) is a key symptom of myalgic encephalomyelitis (ME)
      and chronic fatigue syndrome (CFS). Currently, five PEM-items from the DePaul
      Symptom Questionnaire (DSQ) were recommended as a first step in measuring this
      symptom for patients with ME and CFS by the National Institutes of Health/Centers
      for Disease Control and Prevention (NIH/CDC) Common Data Elements' (CDE) working
      group. The second step in this process, as recommended by the NIH/CDC CDE working
      group, involves assembling information from various sources to confirm the
      presence of PEM. There have not been any efforts, to date, to standardize this
      second-step process in the assessment of PEM. The current study examined whether
      five supplementary items on the DSQ could be used to operationalize the second
      step of the recommendations made by the NIH/CDC CDE working group. The five
      supplementary DSQ PEM duration items correctly categorized patients with ME or
      CFS 81.7% of the time, while incorrectly categorizing multiple sclerosis (MS) and
      post-polio syndrome (PPS) as ME or CFS only 16.6% of the time. The findings
      suggested that a PEM second-step process could be operationalized using
      supplementary DSQ items.

PMID- 30208579
TI  - Body Fatness and Cardiovascular Health in Newborn Infants.
AB  - Birth weight is associated with cardiovascular disease, with those at both ends
      of the spectrum at increased risk. However, birth weight is a crude surrogate of
      fetal growth. Measures of body composition may more accurately identify high risk
      infants. We aimed to determine whether aortic wall thickening, cardiac autonomic
      control, and cardiac structure/function differ in newborns with high or low body
      fatness compared to those with average body fatness. 189 healthy singleton term
      born neonates were recruited and stratified by body fat percentiles (sex and
      gestation-specific). Infants with low body fat had higher aortic intima-media
      thickness (43 um (95% confidence interval (CI) 7, 78), p = 0.02), lower heart
      rate variability (log total power, -0.5 (95% CI -0.8, -0.1), p = 0.008), and
      thicker ventricular walls (posterior wall thickness, 3.1 mm (95% CI 1.6, 4.6), p
      < 0.001) compared to infants with average body fatness. Infants with high body
      fat showed no differences in aortic intima-media thickness (-2 um (95% CI -37,
      33), p = 0.91) or cardiac structure compared to average body fatness, although
      stroke volume (-0.3 mL/kg (95% CI -0.6, -0.0), p = 0.003) and heart rate
      variability were lower (log total power, -0.8 (95% CI -1.1, -0.5), p < 0.001).
      The non-linear association of body fatness with heart rate variability was
      independent of birth weight. Infants born with low or high body fat have altered
      markers of cardiovascular health. Assessment of body fatness alongside birth
      weight may assist in identifying high risk individuals.

PMID- 30208580
TI  - Release of Major Peanut Allergens from Their Matrix under Various pH and
      Simulated Saliva Conditions-Ara h2 and Ara h6 Are Readily Bio-Accessible.
AB  - The oral mucosa is the first immune tissue that encounters allergens upon
      ingestion of food. We hypothesized that the bio-accessibility of allergens at
      this stage may be a key determinant for sensitization. Light roasted peanut flour
      was suspended at various pH in buffers mimicking saliva. Protein concentrations
      and allergens profiles were determined in the supernatants. Peanut protein
      solubility was poor in the pH range between 3 and 6, while at a low pH (1.5) and
      at moderately high pHs (>8), it increased. In the pH range of saliva, between 6.5
      and 8.5, the allergens Ara h2 and Ara h6 were readily released, whereas Ara h1
      and Ara h3 were poorly released. Increasing the pH from 6.5 to 8.5 slightly
      increased the release of Ara h1 and Ara h3, but the recovery remained low
      (approximately 20%) compared to that of Ara h2 and Ara h6 (approximately 100% and
      65%, respectively). This remarkable difference in the extraction kinetics
      suggests that Ara h2 and Ara h6 are the first allergens an individual is exposed
      to upon ingestion of peanut-containing food. We conclude that the peanut
      allergens Ara h2 and Ara h6 are quickly bio-accessible in the mouth, potentially
      explaining their extraordinary allergenicity.

PMID- 30208581
TI  - Seroprevalence of Immunoglobulin E Antibodies against Japanese Cedar Pollen
      Allergens Cry j 1 and Cry j 2 in Dogs Bred in Japan.
AB  - Levels of Japanese cedar pollen (Cryptomeria japonica) have increased in Japan
      and cedar pollinosis caused by Japanese cedar pollen has been reported in dogs.
      Serum levels of immunoglobulin E (IgE) against Cry j 1 and Cry j 2 in dogs raised
      in institutes and treated at veterinary hospitals in Japan were thus
      investigated. A total of 71 sera obtained from two institutes and 87 sera
      obtained from veterinary hospitals in the Hyogo and Kanagawa Prefectures were
      analyzed in this study. Serum levels of IgE were measured using the enzyme-linked
      immunosorbent assay with commercial purified Cry j 1 and Cry j 2. IgE against Cry
      j 1 and Cry j 2 in sera obtained from the two institutes were detected, despite
      the dogs being bred in enclosed areas. Moreover, significant differences were
      noted in the serum levels of IgE against Cry j 1 and Cry j 2 between the two
      institutes. The number of samples showing Cry j 1 or Cry j 2 levels above the cut
      off values was greater in the Kanagawa Prefecture than in the Hyogo Prefecture.
      In total, 14 dogs showed Cry j 1 and Cry j 2 levels greater than the cut-off
      values in the Hyogo Prefecture, and only three such dogs were seen in the
      Kanagawa Prefecture. A significant correlation between serum levels against both
      allergens was observed (r2 = 0.6931, p < 0.0001).

PMID- 30208583
TI  - The Effects of a Health Promotion Program Using Urban Forests and Nursing Student
      Mentors on the Perceived and Psychological Health of Elementary School Children
      in Vulnerable Populations.
AB  - As problems relating to children's health increase, forest therapy has been
      proposed as an alternative. This study examined the effects of a combined health
      promotion program, using urban forests and nursing student mentors, on the
      perceived and psychosocial health of upper-grade elementary students. The quasi
      experimental study ran from June to August 2017, with 52 upper-grade elementary
      students from five community after-school centers. With a purposive sampling,
      they were assigned to either an experimental group (n = 24), who received a 10
      session health promotion program, or to a control group (n = 28). Seven
      undergraduate nursing students participated as mentors. Running over 10 weeks,
      each weekly session consisted of 30 min of health education and 60 min of urban
      forest activities. Data were analyzed by independent t-test, Mann-Whitney U-test,
      paired t-test, or Wilcoxon signed rank test. General characteristics and outcome
      variables of both groups were homogeneous. The experimental group showed
      significant improvement in self-esteem (p = 0.030) and a significant decrease in
      depressive symptoms (p = 0.020) after the intervention, compared to the control
      group. These results suggest that forest healing programs may contribute to the
      spread of health promotion programs that make use of nature.

PMID- 30208584
TI  - Microstructure and Properties of Mg-Zn-Y Alloy Powder Compacted by Equal Channel
      Angular Pressing.
AB  - Mg97Zn1Y2 (at %) alloy with a long period stacking ordered (LPSO) phase has
      attracted a great deal of attention due to its excellent mechanical properties.
      It has been reported that this alloy could be fabricated by warm extrusion of
      rapid solidified alloy powders. In this study, an alternative route combining
      mechanical milling and equal channel angular pressing (ECAP) was selected to
      produce the bulk Mg97Zn1Y2 alloy. Microstructural characterization, mechanical
      properties and corrosion behavior of the ECAP-compacted alloys were studied. The
      as-cast alloy contained alpha-Mg and LPSO-Mg12Zn1Y1 phase. In the as-milled
      powder, the LPSO phase decomposed and formed Mg24Y5 phase. The ECAP-compacted
      alloy had identical phases to those of the as-milled sample. The compacted alloy
      exhibited a hardness of 120 HV and a compressive yield strength of 308 MPa, which
      were higher than those of the as-cast counterpart. The compacted alloy had better
      corrosion resistance, which was attributed to the reduced volume fraction of the
      secondary phase resulting in lower microgalvanic corrosion in the compacted
      alloy. The increase in Y content in the alpha-Mg matrix also contributed to the
      improvement of corrosion resistance.

PMID- 30208582
TI  - Detection and Characterization of Distinct Alphacoronaviruses in Five Different
      Bat Species in Denmark.
AB  - Bat populations harbour a multitude of viruses; some of these are pathogenic or
      potentially pathogenic in other animals or humans. Therefore, it is important to
      monitor the populations and characterize these viruses. In this study, the
      presence of coronaviruses (CoVs) in different species of Danish bats was
      investigated using active surveillance at different geographical locations in
      Denmark. Faecal samples were screened for the presence of CoVs using pan-CoV real
      time RT-PCR assays. The amplicons, obtained from five different species of bats,
      were sequenced. Phylogenetic analysis revealed a species-specific clustering with
      the samples from Myotis daubentonii, showing a close resemblance to coronavirus
      sequences obtained from the same species of bat in Germany and the United
      Kingdom. Our results show, for the first time, that multiple, distinct
      alphacoronaviruses are present in the Danish bat populations.

PMID- 30208586
TI  - Can Plasma Rich in Growth Factors Be Safe for Parental Use? A Safety Study in the
      Canine Model.
AB  - Low invasiveness is the main goal of modern surgery. The use of platelet-rich
      plasma (PRP) is known to be effective in a variety of applications, such as oral,
      maxillofacial, orthopedic, dermatologic and cosmetic surgeries. However, a
      potential ergogenic and carcinogenic effect of PRP derivatives by means of the
      insulin-like growth factor-1 (IGF-1) pathway has been suggested. Because of this
      notion, the purpose of this study is to assess the effect of a commercially
      available PRP-derivative intramuscular injection in the lumbar muscular tissue
      (local effect) and to determine the IGF-1 blood concentration (systemic effect)
      on healthy beagle dogs. Local effect was evaluated by computed tomography (CT)
      scan and echography, and systemic effect was calculated by blood testing on days
      0, 14, 28, 42 and 56. No statistically significant changes were observed; thus,
      PRGF could be considered safe when using therapeutic doses.

PMID- 30208585
TI  - Challenges in Fabrication of Tissue-Engineered Cartilage with Correct Cellular
      Colonization and Extracellular Matrix Assembly.
AB  - A correct articular cartilage ultrastructure regarding its structural components
      and cellularity is important for appropriate performance of tissue-engineered
      articular cartilage. Various scaffold-based, as well as scaffold-free, culture
      models have been under development to manufacture functional cartilage tissue.
      Even decellularized tissues have been considered as a potential choice for
      cellular seeding and tissue fabrication. Pore size, interconnectivity, and
      functionalization of the scaffold architecture can be varied. Increased
      mechanical function requires a dense scaffold, which also easily restricts
      cellular access within the scaffold at seeding. High pore size enhances nutrient
      transport, while small pore size improves cellular interactions and scaffold
      resorption. In scaffold-free cultures, the cells assemble the tissue completely
      by themselves; in optimized cultures, they should be able to fabricate native
      like tissue. Decellularized cartilage has a native ultrastructure, although it is
      a challenge to obtain proper cellular colonization during cell seeding.
      Bioprinting can, in principle, provide the tissue with correct cellularity and
      extracellular matrix content, although it is still an open question as to how the
      correct molecular interaction and structure of extracellular matrix could be
      achieved. These are challenges facing the ongoing efforts to manufacture optimal
      articular cartilage.

PMID- 30208587
TI  - Hair-Growth Potential of Ginseng and Its Major Metabolites: A Review on Its
      Molecular Mechanisms.
AB  - The functional aspect of scalp hair is not only to protect from solar radiation
      and heat/cold exposure but also to contribute to one's appearance and
      personality. Progressive hair loss has a cosmetic and social impact. Hair
      undergoes three stages of hair cycle: the anagen, catagen, and telogen phases.
      Through cyclical loss and new-hair growth, the number of hairs remains relatively
      constant. A variety of factors, such as hormones, nutritional status, and
      exposure to radiations, environmental toxicants, and medications, may affect hair
      growth. Androgens are the most important of these factors that cause androgenic
      alopecia. Other forms of hair loss include immunogenic hair loss, that is,
      alopecia areata. Although a number of therapies, such as finasteride and
      minoxidil, are approved medications, and a few others (e.g., tofacitinib) are in
      progress, a wide variety of structurally diverse classes of phytochemicals,
      including those present in ginseng, have demonstrated hair growth-promoting
      effects in a large number of preclinical studies. The purpose of this review is
      to focus on the potential of ginseng and its metabolites on the prevention of
      hair loss and its underlying mechanisms.

PMID- 30208588
TI  - Characterization and Functional Analysis of FaHsfC1b from Festuca arundinacea
      Conferring Heat Tolerance in Arabidopsis.
AB  - Heat transcription factors (Hsfs) belong to a large gene family classified into
      A, B, and C groups, with classes A and B Hsfs being well-characterized and known
      for their roles in plant tolerance to abiotic stresses. The functions and roles
      of Class C Hsfs are not well-documented. The objectives of this study were to
      characterize a class C Hsf gene (FaHsfC1b) cloned from tall fescue (Festuca
      arundinacea), a perennial grass species, and to determine the physiological
      functions of FaHsfC1b in regulating heat tolerance by overexpressing FaHsfC1b in
      Arabidopsis thaliana. Full length cDNA of FaHsfC1b was cloned and the sequence
      alignment showed that it had high similarity to OsHsfC1b with typical DNA binding
      domain, hydrophobic oligomerization domain, and a nucleus localization signal.
      Transient expression with FaHsfC1b-eGFP in protoplasts of Arabidopsis leaves
      indicated its nucleus localization. qRT-PCR analysis showed that FaHsfC1b
      responded to heat, osmotic, salt, and cold stress in leaves and roots during 48-h
      treatment. Physiological analysis showed that FaHsfC1b overexpression enhanced
      plant survival rate, chlorophyll content, and photochemical efficiency, while it
      resulted in decreases in electrolyte leakage, H2O2 and O2- content under heat
      stress. qRT-PCR showed that endogenous HsfC1 was induced in transgenic plants and
      the expression levels of heat protection protein genes, including several HSPs,
      AtGalSyn1, AtRof1, and AtHSA32, as well as ABA-synthesizing gene (NCED3) were
      significantly upregulated in transgenic plants overexpressing FaHsfC1b under heat
      stress. Our results first demonstrate that HsfC1b plays positive roles in plant
      tolerance to heat stress in association with the induction and upregulation of
      heat-protective genes. HsfC1b may be used as a candidate gene for genetic
      modification of cool-season plant species for improving heat tolerance.

PMID- 30208590
TI  - Fish Oil Supplementation Reduces Inflammation but Does Not Restore Renal Function
      and Klotho Expression in an Adenine-Induced CKD Model.
AB  - BACKGROUND: Chronic kidney disease and inflammation promote loss of Klotho
      expression. Given the well-established anti-inflammatory effects of omega-3 fatty
      acids, we aimed to investigate the effect of fish oil supplementation in a model
      of CKD. METHODS: Male C57BL/6 mice received supplementation with an adenine
      enriched diet (AD, n = 5) or standard diet (CTL, n = 5) for 10 days. Two other
      experimental groups were kept under the adenine diet for 10 days. Following
      adenine withdrawal on the 11th day, the animals returned to a standard diet
      supplemented with fish oil (Post AD-Fish oil, n = 9) or not (Post AD-CTL, n = 9)
      for an additional period of 7 days. RESULTS: Adenine mice exhibited significantly
      higher mean serum urea, creatinine, and renal expression of the pro-inflammatory
      markers Interleukin-6 (IL-6), C-X-C motif chemokine 10 (CXCL10), and Interleukin
      1beta (IL-1beta), in addition to prominent renal fibrosis and reduced renal
      Klotho gene expression compared to the control. Post AD-Fish oil animals
      demonstrated a significant reduction of IL-6, C-X-C motif chemokine 9 (CXCL9),
      and IL-1beta compared to Post AD-CTL animals. However, serum creatinine, renal
      fibrosis, and Klotho were not significantly different in the fish oil-treated
      group. Furthermore, renal histomorphological changes such as tubular dilatation
      and interstitial infiltration persisted despite treatment. CONCLUSIONS: Fish oil
      supplementation reduced renal pro-inflammatory markers but was not able to
      restore renal function nor Klotho expression in an adenine-induced CKD model.

PMID- 30208592
TI  - 3D-Printed PCL/PLA Composite Stents: Towards a New Solution to Cardiovascular
      Problems.
AB  - Biodegradable stents (BRS) offer enormous potential but first they must meet five
      specific requirements: (i) their manufacturing process must be precise; (ii)
      degradation should have minimal toxicity; (iii) the rate of degradation should
      match the recovery rate of vascular tissue; (iv) ideally, they should induce
      rapid endothelialization to restore the functions of vascular tissue, but at the
      same time reduce the risk of restenosis; and (v) their mechanical behavior should
      comply with medical requirements, namely, the flexibility required to facilitate
      placement but also sufficient radial rigidity to support the vessel. Although the
      first three requirements have been comprehensively studied, the last two have
      been overlooked. One possible way of addressing these issues would be to
      fabricate composite stents using materials that have different mechanical,
      biological, or medical properties, for instance, Polylactide Acid (PLA) or
      Polycaprolactone (PCL). However, fashioning such stents using the traditional
      stent manufacturing process known as laser cutting would be impossible. Our work,
      therefore, aims to produce PCL/PLA composite stents using a novel 3D tubular
      printer based on Fused Deposition Modelling (FDM). The cell geometry (shape and
      area) and the materials (PCL and PLA) of the stents were analyzed and correlated
      with 3T3 cell proliferation, degradation rates, dynamic mechanical and radial
      expansion tests to determine the best parameters for a stent that will satisfy
      the five strict BRS requirements. Results proved that the 3D-printing process was
      highly suitable for producing composite stents (approximately 85-95% accuracy).
      Both PCL and PLA demonstrated their biocompatibility with PCL stents presenting
      an average cell proliferation of 12.46% and PLA 8.28% after only 3 days.
      Furthermore, the PCL/PLA composite stents demonstrated their potential in
      degradation, dynamic mechanical and expansion tests. Moreover, and regardless of
      the order of the layers, the composite stents showed (virtually) medium levels of
      degradation rates and mechanical modulus. Radially, they exhibited the virtues of
      PCL in the expansion step (elasticity) and those of PLA in the recoil step
      (rigidity). Results have clearly demonstrated that composite PCL/PLA stents are a
      highly promising solution to fulfilling the rigorous BRS requirements.

PMID- 30208589
TI  - Preconception Micronutrient Supplementation Reduced Circulating Branched Chain
      Amino Acids at 12 Weeks Gestation in an Open Trial of Guatemalan Women Who Are
      Overweight or Obese.
AB  - Elevated branched chain amino acids (BCAAs: valine, leucine, and isoleucine) are
      well-established biomarkers of obesity-associated insulin resistance (IR).
      Mounting evidence suggests that low- and middle-income countries are suffering
      from a "double burden" of both undernutrition (growth stunting) and overnutrition
      (obesity) as these countries undergo a "nutrition transition". The purpose of
      this study was to examine if pre-pregnancy body mass index (BMI, kg/m2) and a
      daily lipid-based micronutrient supplement (LNS, Nutriset) would lead to cross
      sectional differences in circulating levels of branched chain amino acids (BCAAs)
      in Guatemalan women experiencing short stature during early pregnancy. Using data
      from an ongoing randomized controlled trial, Women First, we studied women who
      were normal weight (NW, BMI range for this cohort = 20.1-24.1 kg/m2) or
      overweight/obese (OW/OB, BMI range for this cohort = 25.6-31.9 kg/m2), and
      divided into two groups: those who received daily LNS >= 3 months prior to
      conception through 12 weeks gestation (+LNS), or no LNS (-LNS) (n = 9-10/group).
      BCAAs levels were obtained from dried blood spot card samples (DBS) assessed at
      12 weeks gestation. DBS cards provide a stable, efficient, and reliable means of
      collecting, transporting, and storing blood samples in low resource or field
      settings. Circulating maternal leptin, adiponectin, and insulin were determined
      by immunoassays from serum samples collected at 12 weeks gestation. We found
      maternal pre-pregnancy body mass index (ppBMI) was associated with higher
      circulating BCAAs (r2 = 0.433, p = 0.002) and higher leptin/adiponectin ratio (r
      = 0.466, p = 0.044) in -LNS mothers at 12 weeks gestation. +LNS mothers
      demonstrated no correlations between BCAAs or leptin/adiponectin ratio across
      ppBMI suggesting LNS may be effective at improving metabolic status in OW/OB
      mothers during early pregnancy.

PMID- 30208591
TI  - Correlates of Non-Medical Prescription Drug Misuse Among a Treatment-Seeking
      Population: A Comparison with Illicit Drug Users.
AB  - Prescription drugs (PD) undoubtedly help people with various physical or
      psychiatric ailments. Nevertheless, they are often diverted and misused (use
      without prescription or for purposes/in ways not intended by the prescriber).
      This study compared the sociodemographic and clinical correlates of those who
      misused PDs, used illegal drugs and co-ingested both, to identify those who were
      at a high risk of misusing these drugs. Retrospective analysis of the treatment
      outcome monitoring (TOM) data for the period of 2013-2017 identified 1369
      subjects for the study; 295 patients presented with PD use disorder (PDUD alone),
      811 with illegal drug use disorder (IDUD alone), and 263 had both PDUD and IDUD.
      The study sample included treatment seeking population (Singaporeans and
      permanent residents). TOM data included data collected through direct interviews
      (addiction severity, quality of life) and from the clinical case notes
      (diagnosis, co-morbidities, socio demographic information, etc.). The most
      commonly misused prescription and illegal drugs were benzodiazepines (63.1%) and
      heroin (63.4%), respectively. Those who co-ingested both PD and illegal drugs
      (PDUD+IDUD) had a significantly higher addiction severity score, lower quality of
      life and higher psychiatric co-morbidities than that of IDUD alone at baseline.
      When compared to Chinese patients, Malay and Indian patients had lower odds (p <
      0.05) of PDUD alone and PDUD+IDUD than Chinese patients; divorcees had higher
      odds of PDUD+IDUD than those who were married. Those with primary and secondary
      qualifications had higher odds (2.1 and 2.9 times, respectively) of PDUD+IDUD
      than those with tertiary qualification and those in managerial or professional
      roles had higher odds of PDUD alone than those who were unemployed. Gender,
      ethnicity, marital status, education and occupational classes were associated
      with PDUD and IDUD. These characteristics can be helpful to identify those who
      are at the risk of PDUD and incorporate strict prescription monitoring to their
      care.

PMID- 30208593
TI  - CAR-T Cells Based on Novel BCMA Monoclonal Antibody Block Multiple Myeloma Cell
      Growth.
AB  - The cell-surface protein B cell maturation antigen (BCMA, CD269) has emerged as a
      promising target for CAR-T cell therapy for multiple myeloma. In order to create
      a novel BCMA CAR, we generated a new BCMA monoclonal antibody, clone 4C8A. This
      antibody exhibited strong and selective binding to human BCMA. BCMA CAR-T cells
      containing the 4C8A scFv were readily detected with recombinant BCMA protein by
      flow cytometry. The cells were cytolytic for RPMI8226, H929, and MM1S multiple
      myeloma cells and secreted high levels of IFN-gamma in vitro. BCMA-dependent
      cytotoxicity and IFN-gamma secretion were also observed in response to CHO
      (Chinese Hamster Ovary)-BCMA cells but not to parental CHO cells. In a mouse
      subcutaneous tumor model, BCMA CAR-T cells significantly blocked RPMI8226 tumor
      formation. When BCMA CAR-T cells were given to mice with established RPMI8226
      tumors, the tumors experienced significant shrinkage due to CAR-T cell activity
      and tumor cell apoptosis. The same effect was observed with 3 humanized BCMA-CAR
      T cells in vivo. These data indicate that novel CAR-T cells utilizing the BCMA
      4C8A scFv are effective against multiple myeloma and warrant future clinical
      development.

PMID- 30208595
TI  - Glycosaminoglycan-Protein Interactions by Nuclear Magnetic Resonance (NMR)
      Spectroscopy.
AB  - Nuclear magnetic resonance (NMR) spectroscopy is one of the most utilized and
      informative analytical techniques for investigating glycosaminoglycan (GAG)
      protein complexes. NMR methods that are commonly applied to GAG-protein systems
      include chemical shift perturbation, saturation transfer difference, and
      transferred nuclear Overhauser effect. Although these NMR methods have revealed
      valuable insight into the protein-GAG complexes, elucidating high-resolution
      structural and dynamic information of these often transient interactions remains
      challenging. In addition, preparation of structurally homogeneous and
      isotopically enriched GAG ligands for structural investigations continues to be
      laborious. As a result, understanding of the structure-activity relationship of
      GAGs is still primitive. To overcome these deficiencies, several innovative NMR
      techniques have been developed lately. Here, we review some of the commonly used
      techniques along with more novel methods such as waterLOGSY and experiments to
      examine structure and dynamic of lysine and arginine side chains to identify GAG
      binding sites. We will also present the latest technology that is used to produce
      isotopically enriched as well as paramagnetically tagged GAG ligands. Recent
      results that were obtained from solid-state NMR of amyloid's interaction with GAG
      are also presented together with a brief discussion on computer assisted modeling
      of GAG-protein complexes using sparse experimental data.

PMID- 30208594
TI  - Impacts of Indoxyl Sulfate and p-Cresol Sulfate on Chronic Kidney Disease and
      Mitigating Effects of AST-120.
AB  - Uremic toxins, such as indoxyl sulfate (IS) and p-cresol, or p-cresyl sulfate
      (PCS), are markedly accumulated in the organs of chronic kidney disease (CKD)
      patients. These toxins can induce inflammatory reactions and enhance oxidative
      stress, prompting glomerular sclerosis and interstitial fibrosis, to aggravate
      the decline of renal function. Consequently, uremic toxins play an important role
      in the worsening of renal and cardiovascular functions. Furthermore, they destroy
      the quantity and quality of bone. Oral sorbent AST-120 reduces serum levels of
      uremic toxins in CKD patients by adsorbing the precursors of IS and PCS generated
      by amino acid metabolism in the intestine. Accordingly, AST-120 decreases the
      serum IS levels and reduces the production of reactive oxygen species by
      endothelial cells, to impede the subsequent oxidative stress. This slows the
      progression of cardiovascular and renal diseases and improves bone metabolism in
      CKD patients. Although large-scale studies showed no obvious benefits from adding
      AST-120 to the standard therapy for CKD patients, subsequent sporadic studies may
      support its use. This article summarizes the mechanisms of the uremic toxins, IS,
      and PCS, and discusses the multiple effects of AST-120 in CKD patients.

PMID- 30208596
TI  - Repeated Intrastriatal Botulinum Neurotoxin-A Injection in Hemiparkinsonian Rats
      Increased the Beneficial Effect on Rotational Behavior.
AB  - Injection of botulinum neurotoxin-A (BoNT-A) into the striatum of
      hemiparkinsonian (hemi-PD) rats reduced apomorphine-induced rotation behavior
      significantly, for at least 3 months. Thereafter, rotation behavior increased
      again. We injected hemi-PD rats with 1 ng BoNT-A twice, the second injection
      following 6 months after the first one and tested the rats for apomorphine
      induced rotations and spontaneous motor behaviors, i.e., corridor task and
      stepping test. To test the hypothesis that BoNT-A reduced striatal hypercholinism
      in hemi-PD rats, the acetylcholinesterase inhibitor donepezil was injected prior
      to separate apomorphine-induced rotation tests. In hemi-PD rats, the first BoNT-A
      injection led to a clear reduction of the apomorphine-induced rotations, and the
      second BoNT-A injection to a more massive and prolonged reaction. In hemi-PD rats
      whose apomorphine-induced rotation behavior was strongly reduced by an
      intrastriatal BoNT-A, subsequent donepezil injections led to significant
      increases of the rotation rate. Concerning corridor task and stepping test,
      neither first nor second BoNT-A injections changed hemi-PD rats' behavior
      significantly. The data give evidence for the possibility of repeated
      intrastriatal administrations of BoNT-A, for treatment of motor symptoms in
      experimental hemi-PD over a longer time.

PMID- 30208598
TI  - Novel Porous Phosphorus-Calcium-Magnesium Coatings on Titanium with Copper or
      Zinc Obtained by DC Plasma Electrolytic Oxidation: Fabrication and
      Characterization.
AB  - In this paper, the characteristics of new porous coatings fabricated at three
      voltages in electrolytes based on H3PO4 with calcium nitrate tetrahydrate,
      magnesium nitrate hexahydrate, and copper(II) nitrate trihydrate are presented.
      The SEM, energy dispersive spectroscopy (EDS), glow discharge optical emission
      spectroscopy (GDOES), X-ray photoelectron spectroscopy (XPS), and XRD techniques
      for coating identification were used. It was found that the higher the plasma
      electrolytic oxidation (PEO) (micro arc oxidation (MAO)) voltage, the thicker the
      porous coating with higher amounts of built-in elements coming from the
      electrolyte and more amorphous phase with signals from crystalline Ca(H2PO4)2?H2O
      and/or Ti(HPO4)2?H2O. Additionally, the external parts of the obtained porous
      coatings formed on titanium consisted mainly of Ti4+, Ca2+, Mg2+ and PO43-, HPO42
      , H2PO4-, P2O74- as well as Zn2+ or copper Cu+/Cu2+. The surface should be
      characterized by high biocompatibility, due to the presence of structures based
      on calcium and phosphates, and have bactericidal properties, due to the presence
      of zinc and copper ions. Furthermore, the addition of magnesium ions should
      accelerate the healing of postoperative wounds, which could lead to faster
      patient recovery.

PMID- 30208597
TI  - Clinical Evaluation of INNO-LiPA HPV Genotyping EXTRA II Assay Using the VALGENT
      Framework.
AB  - In this diagnostic test validation study, we assessed the clinical accuracy and
      HPV genotyping performance of the INNO-LiPA HPV Genotyping Extra II (INNO-LiPA)
      within the VALGENT-3 framework. VALGENT is designed to assess the analytical and
      clinical performance of HPV tests with genotyping capacity. The VALGENT-3 panel
      comprised 1300 consecutive cervical cell specimens enriched with 300 samples with
      abnormal cytology obtained from women attending the Slovenian cervical cancer
      screening programme. The INNO-LiPA allows type-specific detection of 32 HPV
      types; however, for the clinical accuracy assessment, we considered it as high
      risk (hr)HPV positive when at least one of the following HPV types was present:
      HPV16, HPV18, HPV31, HPV33, HPV35, HPV39, HPV45, HPV51, HPV52, HPV56, HPV58,
      HPV59, and HPV68. Clinical accuracy for detection of cervical intraepithelial
      neoplasia grade 2 or worse (CIN2+) was compared between INNO-LiPA and Hybrid
      Capture 2 (HC2), which is a standard comparator test for HPV tests used in
      cervical cancer screening. In addition, hrHPV and type-specific detection HPV
      types were compared between INNO-LiPA and Linear Array HPV Genotyping Test
      (Linear Array). The prevalence of hrHPV determined by INNO-LiPA was 17.1% (95%
      CI, 15.0-19.2%) in the screening population. HrHPV testing with INNO-LiPA had a
      sensitivity for CIN2+ of 96.9% (95% CI, 92.1-99.1%) which was non-inferior to HC2
      (relative sensitivity of 1.01; 95% CI, 0.97-1.04; pn.inf = 0.0002) and a
      specificity for <=CIN1 of 85.3% (95% CI, 83.2-87.3%) which was inferior to HC2
      (relative specificity of 0.95; 95% CI, 0.93-0.97; pn.inf = 0.9998). Genotyping
      agreement between INNO-LiPA and Linear Array was excellent for hrHPV, HPV16,
      HPV18, HPV35, HPV45, HPV58 and HPV59, but good or fair for other HPV types. To
      conclude, INNO-LiPA demonstrated non-inferior clinical sensitivity but lower
      specificity compared to HC2 in addition to excellent concordance compared to
      Linear Array for hrHPV and some genotypes.

PMID- 30208599
TI  - Recent Advances in Mitochondria-Targeted Gene Delivery.
AB  - Mitochondria are the energy-producing organelles of cells. Mitochondrial
      dysfunctions link to various syndromes and diseases including myoclonic epilepsy
      and ragged-red fiber disease (MERRF), Leigh syndrome (LS), and Leber hereditary
      optic neuropathy (LHON). Primary mitochondrial diseases often result from
      mutations of mitochondrial genomes and nuclear genes that encode the
      mitochondrial components. However, complete intracellular correction of the
      mutated genetic parts relevant to mitochondrial structures and functions is
      technically challenging. Instead, there have been diverse attempts to provide
      corrected genetic materials with cells. In this review, we discuss recent novel
      physical, chemical and biological strategies, and methods to introduce genetic
      cargos into mitochondria of eukaryotic cells. Effective mitochondria-targeting
      gene delivery systems can reverse multiple mitochondrial disorders by enabling
      cells to produce functional mitochondrial components.

PMID- 30208600
TI  - Malting of Fusarium Head Blight-Infected Rye (Secale cereale): Growth of Fusarium
      graminearum, Trichothecene Production, and the Impact on Malt Quality.
AB  - This project was initiated with the goal of investigating the malt quality of
      winter rye cultivars and hybrids grown in the United States in 2014 and 2015, but
      high levels of deoxynivalenol (DON) were subsequently found in many of the malt
      samples. DON levels in 75% of the investigated rye samples (n = 117) were
      actually below 1.0 mg/kg, as quantified by a gas chromatography combined with
      electron capture detector (GC-ECD). However, 83% of the samples had DON in excess
      of 1.0 mg/kg following malting, and the average DON level in malted rye was 10.6
      mg/kg. In addition, relatively high levels of 3-acetate DON (3-ADON), 15-acetate
      DON (15-ADON), nivalenol (NIV), and DON-3-glucoside (D3G) were observed in some
      rye malts. Our results show that rye grain DON is likely a poor predicator of
      type B trichothecenes in malt in practice, because high levels of malt DON, 15
      ADONm and D3G were produced, even when the rye samples with DON levels below 0.50
      mg/kg were processed. Fusarium Tri5 DNA content in rye was highly associated with
      malt DON levels (r = 0.83) in a small subset of samples (n = 55). The impact of
      Fusarium infection on malt quality was demonstrated by the significant
      correlations between malt DON levels and wort viscosity, beta-glucan content,
      wort color, wort p-coumaric acid content, and total phenolic content. Additional
      correlations of rye Fusarium Tri5 DNA contents with malt diastatic power (DP),
      wort free amino nitrogen (FAN) content, and arabinoxylan content were observed.

PMID- 30208601
TI  - Diuretics, Ca-Antagonists, and Angiotensin-Converting Enzyme Inhibitors Affect
      Zinc Status in Hypertensive Patients on Monotherapy: A Randomized Trial.
AB  - BACKGROUND: Antihypertensive drugs affect mineral metabolism, inflammation, and
      the oxidative state. The aim of this study was to evaluate the effects of
      antihypertensive monopharmacotherapy with diuretics, beta-blockers, calcium
      antagonists (Ca-antagonists), angiotensin-converting enzyme inhibitors (ACE-I),
      and angiotensin II receptor antagonists (ARBs) on zinc (Zn), iron (Fe), and
      copper (Cu) status, parameters of oxidative and inflammatory states, and glucose
      and lipid metabolism in patients with newly diagnosed primary arterial
      hypertension (AH). METHODS: Ninety-eight hypertensive subjects received
      diuretics, beta-blockers, Ca-antagonists, ACE-I, or ARB for three months. Zn, Fe,
      and Cu concentrations were determined in blood, urine, and hair. RESULTS: A
      decrease in zinc serum and erythrocyte concentration and an increase in zinc
      urine concentration were registered after diuretic administration. Ca-antagonists
      led to a decrease in erythrocyte zinc concentration. A decrease in serum zinc
      concentration was observed after ACE-I. A decrease in triglyceride serum
      concentration was noted after ACE-I therapy, and a decrease in tumor necrosis
      factor-alpha serum concentration was seen following administration of Ca
      antagonists. Hypotensive drugs led to decreases in catalase and superoxide
      dismutase serum concentrations. CONCLUSIONS: Three-months of monotherapy with
      diuretics, Ca-antagonists, or ACE-I impairs zinc status in patients with newly
      diagnosed primary AH. Antihypertensive monopharmacotherapy and zinc metabolism
      alterations affect lipid metabolism, the oxidative state, and the inflammatory
      state.

PMID- 30208603
TI  - Ascovirus P64 Homologs: A Novel Family of Large Cationic Proteins That Condense
      Viral Genomic DNA for Encapsidation.
AB  - Eukaryotic dsDNA viruses use small basic protamine-like proteins or histones,
      typically <15 kDa, to condense and encapsidate their genomic (g)DNAs during
      virogenesis. Ascoviruses are large dsDNA (~100-200 kbp) viruses that are
      pathogenic to lepidopteran larvae. Little is known about the molecular basis for
      condensation and encapsidation of their gDNAs. Previous proteomic analysis showed
      that Spodoptera frugiperda ascovirus (SfAV-1a) virions contain a large unique DNA
      binding protein (P64; 64 kDa, pI = 12.2) with a novel architecture proposed to
      condense its gDNA. Here we used physical, biochemical, and transmission electron
      microscopy techniques to demonstrate that P64's basic C-terminal domain condenses
      SfAV-1a gDNA. Moreover, we demonstrate that only P64 homologs in other ascovirus
      virions are unique in stably binding DNA. As similar protein families or
      subfamilies were not identified in extensive database searches, our collective
      data suggest that ascovirus P64 homologs comprise a novel family of atypical
      large viral gDNA condensing proteins.

PMID- 30208602
TI  - Neurocognitive and Psychosocial Outcomes in Pediatric Brain Tumor Survivors.
AB  - The late neurocognitive and psychosocial effects of treatment for pediatric brain
      tumor (PBT) represent important areas of clinical focus and ongoing research.
      Neurocognitive sequelae and associated problems with learning and socioemotional
      development negatively impact PBT survivors' overall health-related quality of
      life, educational attainment and employment rates. Multiple factors including
      tumor features and associated complications, treatment methods, individual
      protective and vulnerability factors and accessibility of environmental supports
      contribute to the neurocognitive and psychosocial outcomes in PBT survivors.
      Declines in overall measured intelligence are common and may persist years after
      treatment. Core deficits in attention, processing speed and working memory are
      postulated to underlie problems with overall intellectual development, academic
      achievement and career attainment. Additionally, psychological problems after PBT
      can include depression, anxiety and psychosocial adjustment issues. Several
      intervention paradigms are briefly described, though to date research on
      innovative, specific and effective interventions for neurocognitive late effects
      is still in its early stages. This article reviews the existing research for
      understanding PBT late effects and highlights the need for innovative research to
      enhance neurocognitive and psychosocial outcomes in PBT survivors.

PMID- 30208605
TI  - Shall We Focus on the Eosinophil to Guide Treatment with Systemic Corticosteroids
      during Acute Exacerbations of COPD?: PRO.
AB  - In an era of precision medicine, it seems regressive that we do not use
      stratified approaches to direct treatment of oral corticosteroids during an
      exacerbation of chronic obstructive pulmonary disease (COPD). This is despite
      evidence suggesting that 40% of COPD patients have eosinophilic inflammation and
      this is an indicator of corticosteroid response. Treatments with oral
      corticosteroids are not always effective and not without harm, with significant
      and increased risk of hyperglycemia, sepsis, and fractures. Eosinophils are
      innate immune cells with an incompletely understood role in the pathology of
      airway disease. They are detected at increased levels in some patients and can be
      measured using non-invasive methods during states of exacerbation and stable
      periods. Despite the eosinophil having an unknown mechanism in COPD, it has been
      shown to be a marker of length of stay in severe hospitalized exacerbations, a
      predictor of risk of future exacerbation and exacerbation type. Although limited,
      promising data has come from one prospective clinical trial investigating the
      eosinophil as a biomarker to direct systemic corticosteroid treatment. This
      identified that there were statistically significant and clinically worsened
      symptoms in patients with low eosinophil levels who were prescribed prednisolone,
      demonstrating the potential utility of the eosinophil. In an era of precision
      medicine our patients' needs are best served by accurate diagnosis, correct
      identification of maximal treatment response and the abolition of harm. The
      peripheral blood eosinophil count could be used towards reaching these aims.

PMID- 30208604
TI  - Hexanoic, Octanoic and Decanoic Acids Promote Basal and Insulin-Induced
      Phosphorylation of the Akt-mTOR Axis and a Balanced Lipid Metabolism in the HepG2
      Hepatoma Cell Line.
AB  - Metabolic illnesses such as non-alcoholic fatty liver disease (NAFLD) are in
      constant increase worldwide. Highly consumed long chain fatty acids (LCFA) are
      among the most obesogenic and steatogenic nutrients. Hepatic steatosis is
      associated with several complications such as insulin resistance. Growing
      evidence points to medium chain fatty acids (MCFA), more efficiently oxidized
      than LCFA, as a promising dietary alternative against NAFLD. However, reports on
      the hepatic effects of MCFA are sometimes conflicting. In this study we exposed
      HepG2 cells, a human hepatocellular model, to 0.25 mM of hexanoic (C6), or
      octanoic (C8), and decanoic (C10) acids separately or in a C8 + C10 equimolar mix
      reflecting commercially available MCFA-rich oils. We found that C6, a poorly
      studied MCFA, as well as C8 and C10 did not provoke the deleterious lipid
      anabolism runaway typically induced by LCFA palmitate. MCFA tended, instead, to
      promote a balanced metabolic profile and were generally non-cytotoxic.
      Accordingly, mitochondrial integrity was mostly preserved following MCFA
      treatment. However, treatments with C8 induced a mitochondrial membrane potential
      decrease, suggesting prolonged exposure to this lipid could be problematic.
      Finally, MCFA treatments maintained optimal insulin sensitivity and even fostered
      basal and insulin-dependent phosphorylation of the Akt-mTOR pathway. Overall,
      MCFA could constitute an effective nutritional tool to manage liver steatosis and
      hepatic insulin resistance.

PMID- 30208606
TI  - Integration of miRNA and mRNA Co-Expression Reveals Potential Regulatory Roles of
      miRNAs in Developmental and Immunological Processes in Calf Ileum during Early
      Growth.
AB  - This study aimed to investigate the potential regulatory roles of miRNAs in calf
      ileum developmental transition from the pre- to the post-weaning period. For this
      purpose, ileum tissues were collected from eight calves at the pre-weaning period
      and another eight calves at the post-weaning period and miRNA expression
      characterized by miRNA sequencing, followed by functional analyses. A total of
      388 miRNAs, including 81 novel miRNAs, were identified. A total of 220 miRNAs
      were differentially expressed (DE) between the two periods. The potential
      functions of DE miRNAs in ileum development were supported by significant
      enrichment of their target genes in gene ontology terms related to metabolic
      processes and transcription factor activities or pathways related to metabolism
      (peroxisomes), vitamin digestion and absorption, lipid and protein metabolism, as
      well as intracellular signaling. Integration of DE miRNAs and DE mRNAs revealed
      several DE miRNA-mRNA pairs with crucial roles in ileum development (bta-miR-374a
      FBXO18, bta-miR-374a-GTPBP3, bta-miR-374a-GNB2) and immune function (bta-miR-15b
      IKBKB). This is the first integrated miRNA-mRNA analysis exploring the potential
      roles of miRNAs in calf ileum growth and development during early life.

PMID- 30208608
TI  - Life Cycle and Genetic Diversity of Symplocarpus nipponicus (Araceae), an
      Endangered Species in Japan.
AB  - Symplocarpus nipponicus, a member of the Araceae family, is an endangered plant
      in several prefectures in Japan. For the conservation of this wild species, we
      investigated the morphology, life cycle, and genetic diversity of three wild
      populations. By fixed-point observation over several years, we found that it
      takes at least four years for the plant to set the inflorescences consisting of
      spadices and spathes, and another two years for it to set mature seeds. To
      examine the genetic diversity in the wild population, we developed 11 novel
      microsatellite markers and investigated the genetic variation in three
      populations in Kyoto Prefecture: Ayabe, Hanase, and Momoi. The Ayabe population
      carried less genetic variation than the other two areas, suggesting the isolation
      of the habitat and thus a higher risk of extinction. Our results provide basic
      knowledge of the ecological aspects of S. nipponicus, as well as molecular
      techniques for the assessment of its genetic diversity, and thus are useful for
      the conservation of this endangered species.

PMID- 30208609
TI  - Designing Efficient Low-Cost Paper-Based Sensing Plasmonic Nanoplatforms.
AB  - Paper-based platforms can be a promising choice as portable sensors due to their
      low-cost and facile fabrication, ease of use, high sensitivity, specificity and
      flexibility. By combining the qualities of these 3D platforms with the optical
      properties of gold nanoparticles, it is possible to create efficient nanodevices
      with desired biosensing functionalities. In this work, we propose a new plasmonic
      paper-based dual localized surface plasmon resonance-surface-enhanced Raman
      scattering (LSPR-SERS) nanoplatform with improved detection abilities in terms of
      high sensitivity, uniformity and reproducibility. Specifically, colloidal gold
      nanorods (GNRs) with a well-controlled plasmonic response were firstly
      synthesized and validated as efficient dual LSPR-SERS nanosensors in solution
      using the p-aminothiophenol (p-ATP) analyte. GNRs were then efficiently
      immobilized onto the paper via the immersion approach, thus obtaining plasmonic
      nanoplatforms with a modulated LSPR response. The successful deposition of the
      nanoparticles onto the cellulose fibers was confirmed by LSPR measurements, which
      demonstrate the preserved plasmonic response after immobilization, as well as by
      dark-field microscopy and scanning electron microscopy investigations, which
      confirm their uniform distribution. Finally, a limit of detection for p-ATP as
      low as 10-12 M has been achieved by our developed SERS-based paper nanoplatform,
      proving that our optimized plasmonic paper-based biosensing design could be
      further considered as an excellent candidate for miniaturized biomedical
      applications.

PMID- 30208611
TI  - Gloeothece sp. as a Nutraceutical Source-An Improved Method of Extraction of
      Carotenoids and Fatty Acids.
AB  - The nutraceutical potential of microalgae boomed with the exploitation of new
      species and sustainable extraction systems of bioactive compounds. Thus, a
      laboratory-made continuous pressurized solvent extraction system (CPSE) was built
      to optimize the extraction of antioxidant compounds, such as carotenoids and
      PUFA, from a scarcely studied prokaryotic microalga, Gloeothece sp. Following
      "green chemical principles" and using a GRAS solvent (ethanol), biomass amount,
      solvent flow-rate/pressure, temperature and solvent volume-including solvent
      recirculation-were sequentially optimized, with the carotenoids and PUFA content
      and antioxidant capacity being the objective functions. Gloeothece sp. bioactive
      compounds were best extracted at 60  degrees C and 180 bar. Recirculation of
      solvent in several cycles (C) led to an 11-fold extraction increase of beta
      carotene (3C) and 7.4-fold extraction of C18:2 n6 t (5C) when compared to
      operation in open systems. To fully validate results CPSE, this system was
      compared to a conventional extraction method, ultrasound assisted extraction
      (UAE). CPSE proved superior in extraction yield, increasing total carotenoids
      extraction up 3-fold and total PUFA extraction by ca. 1.5-fold, with particular
      extraction increase of 18:3 n3 by 9.6-fold. Thus, CPSE proved to be an efficient
      and greener extraction method to obtain bioactive extract from Gloeothece sp. for
      nutraceutical purposes-with low levels of resources spent, while lowering costs
      of production and environmental impacts.

PMID- 30208610
TI  - Prevalence of Sexual Violence in Migrants, Applicants for International
      Protection, and Refugees in Europe: A Critical Interpretive Synthesis of the
      Evidence.
AB  - (1) Background: Sexual violence (SV) is a major public health problem, with
      negative socio-economic, physical, mental, sexual, and reproductive health
      consequences. Migrants, applicants for international protection, and refugees
      (MARs) are vulnerable to SV. Since many European countries are seeing high
      migratory pressure, the development of prevention strategies and care paths
      focusing on victimised MARs is highly needed. To this end, this study reviews
      evidence on the prevalence of SV among MAR groups in Europe and the challenges
      encountered in research on this topic. (2) Methods: A critical interpretive
      synthesis of 25 peer-reviewed academic studies and 22 relevant grey literature
      documents was conducted based on a socio-ecological model. (3) Results: Evidence
      shows that SV is highly frequent in MARs in Europe, yet comparison with other
      groups is still difficult. Methodologically and ethically sound representative
      studies comparing between populations are still lacking. Challenges in
      researching SV in MARs are located at the intrapersonal, interpersonal,
      community, societal, and policy levels. (4) Conclusions: Future research should
      start with a clear definition of the concerned population and acts of SV to
      generate comparable data. Participatory qualitative research approaches could be
      applied to better grasp the complexity of interplaying determinants of SV in
      MARs.

PMID- 30208607
TI  - Aptamers as Diagnostic Tools in Cancer.
AB  - Cancer is the second leading cause of death worldwide. Researchers have been
      working hard on investigating not only improved therapeutics but also on early
      detection methods, both critical to increasing treatment efficacy, and developing
      methods for disease prevention. The use of nucleic acids, or aptamers, has
      emerged as more specific and accurate cancer diagnostic and therapeutic tools.
      Aptamers are single-stranded DNA or RNA molecules that recognize specific targets
      based on unique three-dimensional conformations. Despite the fact aptamer
      development has been mainly restricted to laboratory settings, the unique
      attributes of these molecules suggest their high potential for clinical advances
      in cancer detection. Aptamers can be selected for a wide range of targets, and
      also linked with an extensive variety of diagnostic agents, via physical or
      chemical conjugation, to improve previously-established detection methods or to
      be used as novel biosensors for cancer diagnosis. Consequently, herein we review
      the principal considerations and recent updates in cancer detection and imaging
      through aptamer-based molecules.

PMID- 30208612
TI  - Characterization of the XTH Gene Family: New Insight to the Roles in Soybean
      Flooding Tolerance.
AB  - Xyloglucan endotransglycosylases/hydrolases (XTHs) are a class of enzymes
      involved in the construction and remodeling of cellulose/xyloglucan crosslinks
      and play an important role in regulating cell wall extensibility. However, little
      is known about this class of enzymes in soybean. Here, 61 soybean XTH genes
      (GmXTHs) were identified and classified into three subgroups through comparative
      phylogenetic analysis. Genome duplication greatly contributed to the expansion of
      GmXTH genes in soybean. A conserved amino acid motif responsible for the
      catalytic activity was identified in all GmXTHs. Further expression analysis
      revealed that most GmXTHs exhibited a distinct organ-specific expression pattern,
      and the expression level of many GmXTH genes was significantly associated with
      ethylene and flooding stress. To illustrate a possible role of XTH genes in
      regulating stress responses, the ArabidopsisAtXTH31 gene was overexpressed in
      soybean. The generated transgenic plants exhibited improved tolerance to flooding
      stress, with a higher germination rate and longer roots/hypocotyls during the
      seedling stage and vegetative growth stages. In summary, our combined
      bioinformatics and gene expression pattern analyses suggest that GmXTH genes play
      a role in regulating soybean stress responses. The enhanced soybean flooding
      tolerance resulting from the expression of an Arabidopsis XTH also supports the
      role of XTH genes in regulating plant flooding stress responses.

PMID- 30208613
TI  - Impact of the Regional Network for AMI in the Management of STEMI on Care
      Processes, Outcomes and Health Inequities in the Veneto Region, Italy.
AB  - Cardiovascular diseases are a leading cause of death in Europe. Outcomes in terms
      of mortality and health equity in the management of patients with ST-Elevation
      Myocardial Infarction (STEMI) are influenced by health care service organization.
      The main aim of the present study was to examine the impact of the new
      organizational model of the Veneto Region's network for Acute Myocardial
      Infarction (AMI) to facilitate primary percutaneous coronary intervention (PCI)
      on STEMI, and its efficacy in reducing health inequities. A retrospective cohort
      study was conducted on HDRs in the Veneto Region for the period 2007-2016,
      analyzing 65,261 hospitalizations for AMI. The proportion of patients with STEMI
      treated with PCI within 24 h increased significantly for men and women, and was
      statistically much higher for patients over 75 years of age (APC, 75-84: 9.8;
      >85: 12.5) than for younger patients (APC, <45: 3.3; 45-64: 4.9), with no
      difference relating to citizenship. The reduction in in-hospital, STEMI-related
      mortality was only statistically significant for patients aged 75-84 (APC: -3.0 [
      4.5;-1.6]), and for Italians (APC: -1.9 [-3.2;-0.6]). Multivariate analyses
      confirmed a reduction in the disparities between socio-demographic categories.
      Although the new network improved the care process and reduced health care
      disparities in all subgroups, these efforts did not result in the expected
      survival benefit in all patient subgroups.

PMID- 30208614
TI  - Pyropia yezoensis Protein Supplementation Prevents Dexamethasone-Induced Muscle
      Atrophy in C57BL/6 Mice.
AB  - We investigated the protective effects of Pyropia yezoensis crude protein (PYCP)
      against dexamethasone (DEX)-induced myotube atrophy and its underlying
      mechanisms. DEX (3 mg/kg body weight, intraperitoneal injection) and PYCP (150
      and 300 mg/kg body weight, oral) were administrated to mice for 18 days, and the
      effects of PYCP on DEX-induced muscle atrophy were evaluated. Body weight, calf
      thickness, and gastrocnemius and tibialis anterior muscle weight were
      significantly decreased by DEX administration (p < 0.05), while PYCP
      supplementation effectively prevented the DEX-induced decrease in body weight,
      calf thickness, and muscle weight. PYCP supplementation also attenuated the DEX
      induced increase in serum glucose, creatine kinase, and lactate dehydrogenase
      levels. Additionally, PYCP supplementation reversed DEX-induced muscle atrophy
      via the regulation of the insulin-like growth factor-I/protein kinase B/rapamycin
      sensitive mTOR complex I/forkhead box O signaling pathway. The mechanistic
      investigation revealed that PYCP inhibited the ubiquitin-proteasome and autophagy
      lysosome pathways in DEX-administrated C57BL/6 mice. These findings demonstrated
      that PYCP increased protein synthesis and decreased protein breakdown to prevent
      muscle atrophy. Therefore, PYCP supplementation appears to be useful for
      preventing muscle atrophy.

PMID- 30208615
TI  - Highly Substituted Benzophenone Aldehydes and Eremophilane Derivatives from the
      Deep-Sea Derived Fungus Phomopsis lithocarpus FS508.
AB  - Five new benzophenone derivatives named tenellones D-H (1-5), sharing a rare
      naturally occurring aldehyde functionality in this family, and a new eremophilane
      derivative named lithocarin A (7), together with two known compounds (6 and 8),
      were isolated from the deep marine sediment-derived fungus Phomopsis lithocarpus
      FS508. All of the structures for these new compounds were fully characterized and
      established on the basis of extensive spectroscopic interpretation and X-ray
      crystallographic analysis. Compound 5 exhibited cytotoxic activity against HepG-2
      and A549 cell lines with IC50 values of 16.0 and 17.6 MUM, respectively.

PMID- 30208616
TI  - Improvement of Left Ventricular Ejection Time Measurement in the Impedance
      Cardiography Combined with the Reflection Photoplethysmography.
AB  - Cardiac stroke volume (SV) is an essential hemodynamic indicator that can be used
      to assess whether the pump function of the heart is normal. Non-invasive SV
      measurement is currently performed using the impedance cardiography (ICG). In
      this technology, left ventricular ejection time (LVET) is an important parameter
      which can be determined from the ICG signals. However, the ICG signals are
      inherently susceptible to artificial noise interference, which leads to an
      inaccurate LVET measurement and then yields an error in the calculation of SV.
      Therefore, the goal of the study was to measure LVETs using both the transmission
      and reflection photoplethysmography (PPG), and to assess whether the measured
      LVET was more accurate by the PPG signal than the ICG signal. The LVET measured
      by the phonocardiography (PCG) was used as the standard for comparing with those
      by the ICG and PPG. The study recruited ten subjects whose LVETs were
      simultaneously measured by the ICG using four electrodes, the reflection PPG
      using neck sensors (PPGneck) and the transmission PPG using finger sensors
      (PPGfinger). In each subject, ten LVETs were obtained from ten heartbeats
      selected properly from one-minute recording. The differences of the measured
      LVETs between the PCG and one of the ICG, PPGneck and PPGfinger were -68.2 +/-
      148.6 ms, 4.8 +/- 86.5 ms and -7.0 +/- 107.5 ms, respectively. As compared with
      the PCG, both the ICG and PPGfinger underestimated but the PPGneck overestimated
      the LVETs. Furthermore, the measured LVET by the PPGneck was the closest to that
      by the PCG. Therefore, the PPGneck may be employed to improve the LVET
      measurement in applying the ICG for continuous monitoring of SV in clinical
      settings.

PMID- 30208618
TI  - A Comparative Study on the Mechanical Properties of a Polymer-Infiltrated Ceramic
      Network Material Used for the Fabrication of Hybrid Abutment.
AB  - Polymer-infiltrated ceramic-network (PICN) material is a new type of material
      used for the hybrid abutments of dental implants. This study aimed to compare
      flexural strength, bond strengths, and fracture-resistance values of PICN with
      lithium disilicate ceramic (LDS) and to evaluate the effect of thermocycling on
      the tested parameters. Twenty specimens were fabricated using computer-aided
      design and manufacturing (CAD-CAM) technology for each material according to
      three-point bending (n = 10), microshear bond strength (uSBS), and a fracture
      resistance test (hybrid abutment, n = 10). All specimens of each test group were
      divided into two subgroups, thermocycled or nonthermocycled. Hybrid abutments
      were cemented on titanium insert bases and then fixed on implants to compare
      fracture resistance. Failure loads were recorded for each test and data were
      statistically analyzed. Thermocycling decreased bond strength to the resin luting
      agent and the fracture-resistance values of both materials (p < 0.001), whereas
      flexural-strength values were not affected. LDS ceramic showed significantly
      higher flexural strength, bond strength, and fracture-resistance values than PICN
      material (p < 0.001). Within the limitations of this study, LDS may be a
      preferable hybrid-abutment material to PICN in terms of mechanical and bonding
      properties.

PMID- 30208619
TI  - Health-Related Quality of Life after Pediatric Severe Sepsis.
AB  - BACKGROUND: Pediatric severe sepsis is a public health problem with significant
      morbidities in those who survive. In this article, we aim to present an overview
      of the important studies highlighting the limited data available pertaining to
      long-term outcomes of survivors of pediatric severe sepsis. MATERIALS AND
      METHODS: A review of literature available was conducted using PUBMED/Medline on
      pediatric severe sepsis outcomes. Long-term outcomes and health-related quality
      of life (HRQL) following severe sepsis was defined as any outcome occurring after
      discharge from the hospital following an episode of severe sepsis which affected
      either the survivor or the survivor's family members. RESULTS: Many children are
      discharged with worse clinical and functional outcomes, depending on their
      diagnosis, treatments received, psychological effects, and the impact of their
      illness on their parents. Additionally, they utilize healthcare services more
      than their peers and are often readmitted soon after discharge. However,
      pediatric HRQL studies with worthwhile outcome measures are limited and the
      current data on pediatric sepsis is mainly retrospective. CONCLUSIONS: There is
      significant and longstanding morbidity seen in children and their families
      following a severe sepsis illness. Further prospective data are required to study
      the long-term outcomes of sepsis in the pediatric population.

PMID- 30208617
TI  - Viruses of Eukaryotic Algae: Diversity, Methods for Detection, and Future
      Directions.
AB  - The scope for ecological studies of eukaryotic algal viruses has greatly improved
      with the development of molecular and bioinformatic approaches that do not
      require algal cultures. Here, we review the history and perceived future
      opportunities for research on eukaryotic algal viruses. We begin with a summary
      of the 65 eukaryotic algal viruses that are presently in culture collections,
      with emphasis on shared evolutionary traits (e.g., conserved core genes) of each
      known viral type. We then describe how core genes have been used to enable
      molecular detection of viruses in the environment, ranging from PCR-based
      amplification to community scale "-omics" approaches. Special attention is given
      to recent studies that have employed network-analyses of -omics data to predict
      virus-host relationships, from which a general bioinformatics pipeline is
      described for this type of approach. Finally, we conclude with acknowledgement of
      how the field of aquatic virology is adapting to these advances, and highlight
      the need to properly characterize new virus-host systems that may be isolated
      using preliminary molecular surveys. Researchers can approach this work using
      lessons learned from the Chlorella virus system, which is not only the best
      characterized algal-virus system, but is also responsible for much of the
      foundation in the field of aquatic virology.

PMID- 30208620
TI  - Cellular Sources and Regional Variations in the Expression of the
      Neuroinflammatory Marker Translocator Protein (TSPO) in the Normal Brain.
AB  - The inducible expression of the mitochondrial translocator protein 18 kDa (TSPO)
      by activated microglia is a prominent, regular feature of acute and chronic
      progressive brain pathology. This expression is also the rationale for the
      continual development of new TSPO binding molecules for the diagnosis of
      "neuroinflammation" by molecular imaging. However, there is in the normal brain
      an ill-defined, low-level constitutive expression of TSPO. Taking advantage of
      healthy TSPO knockout mouse brain tissue to validate TSPO antibody specificity,
      this study uses immunohistochemistry to determine the regional distribution and
      cellular sources of TSPO in the normal mouse brain. Fluorescence microscopy
      revealed punctate TSPO immunostaining in vascular endothelial cells throughout
      the brain. In the olfactory nerve layers and glomeruli of the olfactory bulb,
      choroid plexus and ependymal layers, we confirm constitutive TSPO expression
      levels similar to peripheral organs, while some low TSPO expression is present in
      regions of known neurogenesis, as well as cerebellar Purkinje cells. The
      distributed-sparse expression of TSPO in endothelial mitochondria throughout the
      normal brain can be expected to give rise to a low baseline signal in TSPO
      molecular imaging studies. Finally, our study emphasises the need for valid and
      methodologically robust verification of the selectivity of TSPO ligands through
      the use of TSPO knockout tissues.

PMID- 30208621
TI  - Chiral Diol-Based Organocatalysts in Enantioselective Reactions.
AB  - Organocatalysis has emerged as a powerful synthetic tool in organic chemistry in
      the last few decades. Among various classes of organocatalysis, chiral diol-based
      scaffolds, such as BINOLs, VANOLs, and tartaric acid derivatives, have been
      widely used to induce enantioselectivity due to the ability of the hydroxyls to
      coordinate with the Lewis acidic sites of reagents or substrates and create a
      chiral environment for the transformation. In this review, we will discuss the
      applications of these diol-based catalysts in different types of reactions,
      including the scopes of reactions and the modes of catalyst activation. In
      general, the axially chiral aryl diol BINOL and VANOL derivatives serve as the
      most competent catalyst for most examples, but examples of exclusive success
      using other scaffolds, herein, suggests that they should not be overlooked.
      Lastly, the examples, to date, are mainly from tartrate and biaryl diol
      catalysts, suggesting that innovation may be available from new diol scaffolds.

PMID- 30208622
TI  - Lipoic Acid Prevents High-Fat Diet-Induced Hepatic Steatosis in Goto Kakizaki
      Rats by Reducing Oxidative Stress Through Nrf2 Activation.
AB  - Prevention of hepatic fat accumulation may be an important approach for liver
      diseases due to the increased relevance of hepatic steatosis in this field. This
      study was conducted to investigate the effects of the antioxidant alpha-lipoic
      acid (alpha-LA) on hepatic steatosis, hepatocellular function, and oxidative
      stress in a model of type 2 diabetes fed with a high fat diet (HFD). Goto
      Kakizaki rats were randomly divided into four groups. The first group received
      only a standard rat diet (control GK) including groups 2 (HFD), 3 (vehicle
      group), and 4 (alpha-LA group), which were given HFD, ad libitum during three
      months. Wistar rats are the non-diabetic control group. Carbohydrate and lipid
      metabolism, liver function, plasma and liver tissue malondialdehyde (MDA), liver
      GSH, tumor necrosis factor-alpha (TNF-alpha) and nuclear factor E2 (erythroid
      derived 2)-related factor-2 (Nrf2) levels were assessed in the different groups.
      Liver function was assessed using quantitative hepatobiliary scintigraphy, serum
      aspartate, and alanine aminotransferases (AST, ALT), alkaline phosphatase, gamma
      glutamyltranspeptidase, and bilirubin levels. Histopathologically steatosis and
      fibrosis were evaluated. Type 2 diabetic animals fed with HFD showed a marked
      hepatic steatosis and a diminished hepatic extraction fraction and both were
      fully prevented with alpha-LA. Plasma and liver tissue MDA and hepatic TNF-alpha
      levels were significantly higher in the HFD group when compared with the control
      group and significantly lower in the alpha-LA group. Systemic and hepatic
      cholesterol, triglycerides, and serum uric acid levels were higher in
      hyperlipidemic GK rats and fully prevented with alpha-LA. In addition, nuclear
      Nrf2 activity was significantly diminished in GK rats and significantly augmented
      after alpha-LA treatment. In conclusion, alpha-LA strikingly ameliorates
      steatosis in this animal model of diabetes fed with HFD by decrementing the
      inflammatory marker TNF-alpha and reducing oxidative stress. alpha-LA might be
      considered a useful therapeutic tool to prevent hepatic steatosis by incrementing
      antioxidant defense systems through Nrf2 and consequently decreasing oxidative
      stress and inflammation in type 2 diabetes.

PMID- 30208625
TI  - Novel Titania Nanocoatings Produced by Anodic Oxidation with the Use of
      Cyclically Changing Potential: Their Photocatalytic Activity and
      Biocompatibility.
AB  - The anodic oxidation of Ti6Al4V substrate surfaces with the use of cyclically
      changing potential enabled the production of novel titania nanocoatings.
      Morphologically different coatings were prepared in the ethylene glycol-based
      electrolyte with diluted HF and various amounts of water. The structure of the
      produced surface materials was characterized by X-ray diffraction, Raman
      spectroscopy, and diffuse reflectance infrared Fourier transform spectroscopy.
      Their morphology was visualized by scanning electron microscopy. The
      photocatalytic efficiency of produced materials was studied by the observation of
      methylene blue degradation under UV irradiation. Their biointegration properties
      were established on the basis of immunological assays, which checked murine
      fibroblasts adhesion and proliferation on novel coatings. The obtained results
      pointed out to both high biocompatibility, as well as the photoactivity of one of
      the obtained nanocoatings, allowing trusting in the applicative nature of this
      material.

PMID- 30208624
TI  - Discovery of lahS as a Global Regulator of Environmental Adaptation and Virulence
      in Aeromonas hydrophila.
AB  - Aeromonas hydrophila is an important aquatic microorganism that can cause fish
      hemorrhagic septicemia. In this study, we identified a novel LysR family
      transcriptional regulator (LahS) in the A. hydrophila Chinese epidemic strain NJ
      35 from a library of 947 mutant strains. The deletion of lahS caused bacteria to
      exhibit significantly decreased hemolytic activity, motility, biofilm formation,
      protease production, and anti-bacterial competition ability when compared to the
      wild-type strain. In addition, the determination of the fifty percent lethal dose
      (LD50) in zebrafish demonstrated that the lahS deletion mutant (DeltalahS) was
      highly attenuated in virulence, with an approximately 200-fold increase in LD50
      observed as compared with that of the wild-type strain. However, the DeltalahS
      strain exhibited significantly increased antioxidant activity (six-fold). Label
      free quantitative proteome analysis resulted in the identification of 34
      differentially expressed proteins in the DeltalahS strain. The differentially
      expressed proteins were involved in flagellum assembly, metabolism, redox
      reactions, and cell density induction. The data indicated that LahS might act as
      a global regulator to directly or indirectly regulate various biological
      processes in A. hydrophila NJ-35, contributing to a greater understanding the
      pathogenic mechanisms of A. hydrophila.

PMID- 30208627
TI  - Functional Scanning of Apple Geminivirus Proteins as Symptom Determinants and
      Suppressors of Posttranscriptional Gene Silencing.
AB  - Apple geminivirus (AGV) is a recently identified geminivirus which is isolated
      from the apple tree in China. We carried out functional scanning of apple
      geminivirus proteins as symptom determinants and suppressors of
      posttranscriptional gene silencing (PTGS). Our results indicated that AGV V2 is
      an important virulence factor localized to the nucleus and cytoplasm that
      suppresses PTGS and induces severe symptoms of crinkling and necrosis. AGV C1 is
      also a virulence determinant which elicits systemic necrosis when expressed from
      a PVX-based vector. The AGV C4 is targeted to cytoplasm, plasma membrane,
      nucleus, and chloroplasts. The inoculation of PVX-C4 on N. benthamiana induced
      severe upward leaf curling, which implied that AGV C4 also functions as a symptom
      determinant, and mutation analyses suggested that the acylated residues on Gly2
      and Cys8 play important roles in its subcellular localization and symptom
      development.

PMID- 30208623
TI  - Protein Tyrosine Phosphatases as Potential Regulators of STAT3 Signaling.
AB  - The signal transducer and activator of transcription 3 (STAT3) protein is a major
      transcription factor involved in many cellular processes, such as cell growth and
      proliferation, differentiation, migration, and cell death or cell apoptosis. It
      is activated in response to a variety of extracellular stimuli including
      cytokines and growth factors. The aberrant activation of STAT3 contributes to
      several human diseases, particularly cancer. Consequently, STAT3-mediated
      signaling continues to be extensively studied in order to identify potential
      targets for the development of new and more effective clinical therapeutics.
      STAT3 activation can be regulated, either positively or negatively, by different
      posttranslational mechanisms including serine or tyrosine
      phosphorylation/dephosphorylation, acetylation, or demethylation. One of the
      major mechanisms that negatively regulates STAT3 activation is dephosphorylation
      of the tyrosine residue essential for its activation by protein tyrosine
      phosphatases (PTPs). There are seven PTPs that have been shown to dephosphorylate
      STAT3 and, thereby, regulate STAT3 signaling: PTP receptor-type D (PTPRD), PTP
      receptor-type T (PTPRT), PTP receptor-type K (PTPRK), Src homology region 2 (SH
      2) domain-containing phosphatase 1(SHP1), SH-2 domain-containing phosphatase 2
      (SHP2), MEG2/PTP non-receptor type 9 (PTPN9), and T-cell PTP (TC-PTP)/PTP non
      receptor type 2 (PTPN2). These regulators have great potential as targets for the
      development of more effective therapies against human disease, including cancer.

PMID- 30208626
TI  - Nematobacterial Complexes and Insect Hosts: Different Weapons for the Same War.
AB  - Entomopathogenic nematodes (EPNs) are widely used as biological control agents
      against insect pests, the efficacy of these organisms strongly depends on the
      balance between the parasitic strategies and the immune response of the host.
      This review summarizes roles and relationships between insect hosts and two well
      known EPN species, Steinernema feltiae and Steinernema carpocapsae and outlines
      the main mechanisms of immune recognition and defense of insects. Analyzing
      information and findings about these EPNs, it is clear that these two species use
      shared immunosuppression strategies, mainly mediated by their symbiotic bacteria,
      but there are differences in both the mechanism of evasion and interference of
      the two nematodes with the insect host immune pathways. Based on published data,
      S. feltiae takes advantage of the cross reaction between its body surface and
      some host functional proteins, to inhibit defensive processes; otherwise,
      secretion/excretion products from S. carpocapsae seem to be the main nematode
      components responsible for the host immunosuppression.

PMID- 30208628
TI  - Exposure to Secondhand Smoke and Risk of Cancer in Never Smokers: A Meta-Analysis
      of Epidemiologic Studies.
AB  - This is first meta-analysis to evaluate cancer risk associated with secondhand
      smoking across all cancers. A literature search was conducted for articles
      published before June 2014 on Pubmed, SCOPUS, Cochrane library, and CINAHL, and
      40 articles on secondhand smoke and the prevalence of cancer among never smokers
      were selected for final analysis as per the inclusion criteria. Of the 40
      articles, 27 were case-control studies and 13 were prospective cohort studies.
      With respect to overall cancer risk, odds ratio (OR) involving never smokers with
      significant exposure to secondhand smoke compared to never smokers without such
      exposure was 1.163 (95%CI 1.058-1.279). Subgroup meta-analyses by study design
      showed significant positive associations for both case-control studies and
      prospective cohort studies (OR 1.165, 95%CI 1.029-1.320; and OR 1.160, 95%CI
      1.002-1.343, respectively). The association was stronger in the case of females
      (OR 1.253, 95%CI 1.142-1.374), lung cancer (OR 1.245, 95%CI 1.026-1.511), and
      breast cancer (OR 1.235, 95%CI 1.102-1.385). Secondhand smoking may increase the
      overall risk of cancer for never smokers, particularly lung and breast cancer,
      and especially in women. Strict implementation of smoking cessation programs
      should be encouraged, not only to reduce active smoking but also to limit
      exposure to secondhand smoke.

PMID- 30208631
TI  - Use of Linagliptin for the Management of Medicine Department Inpatients with Type
      2 Diabetes in Real-World Clinical Practice (Lina-Real-World Study).
AB  - The use of noninsulin antihyperglycaemic drugs in the hospital setting has not
      yet been fully described. This observational study compared the efficacy and
      safety of the standard basal-bolus insulin regimen versus a dipeptidyl peptidase
      4 inhibitor (linagliptin) plus basal insulin in medicine department inpatients in
      real-world clinical practice. We retrospectively enrolled non-critically ill
      patients with type 2 diabetes with mild to moderate hyperglycaemia and no
      injectable treatments at home who were treated with a hospital antihyperglycaemic
      regimen (basal-bolus insulin, or linagliptin-basal insulin) between January 2016
      and December 2017. Propensity score was used to match patients in both treatment
      groups and a comparative analysis was conducted to test the significance of
      differences between groups. After matched-pair analysis, 227 patients were
      included per group. No differences were shown between basal-bolus versus
      linagliptin-basal regimens for the mean daily blood glucose concentration after
      admission (standardized difference = 0.011), number of blood glucose readings
      between 100-140 mg/dL (standardized difference = 0.017) and >200 mg/dL
      (standardized difference = 0.021), or treatment failures (standardized difference
      = 0.011). Patients on basal-bolus insulin received higher total insulin doses and
      a higher daily number of injections (standardized differences = 0.298 and 0.301,
      respectively). Basal and supplemental rapid-acting insulin doses were similar
      (standardized differences = 0.003 and 0.012, respectively). There were no
      differences in hospital stay length (standardized difference = 0.003),
      hypoglycaemic events (standardized difference = 0.018), or hospital complications
      (standardized difference = 0.010) between groups. This study shows that in real
      world clinical practice, the linagliptin-basal insulin regimen was as effective
      and safe as the standard basal-bolus regimen in non-critical patients with type 2
      diabetes with mild to moderate hyperglycaemia treated at home without injectable
      therapies.

PMID- 30208630
TI  - Leukocyte Immunoglobulin-Like Receptors A2 and A6 are Expressed in Avian
      Macrophages and Modulate Cytokine Production by Activating Multiple Signaling
      Pathways.
AB  - The activating leukocyte immunoglobulin-like receptors (LILRAs) play an important
      role in innate immunity. However, most of the LILRA members have not been
      characterized in avian species including chickens. The present study is the first
      attempt at cloning, structural analysis and functional characterization of two
      LILRAs (LILRA2 and LILRA6) in chickens. Multiple sequence alignments and
      construction of a phylogenetic tree of chicken LILRA2 and LILRA6 with mammalian
      proteins revealed high conservation between chicken LILRA2 and LILRA6 and a close
      relationship between the chicken and mammalian proteins. The mRNA expression of
      LILRA2 and LILRA6 was high in chicken HD11 macrophages and the small intestine
      compared to that in several other tissues and cells tested. To examine the
      function of LILRA2 and LILRA6 in chicken immunity, LILRA2 and LILRA6 were
      transfected into HD11 cells. Our findings indicated that LILRA2 and LILRA6 are
      associated with the phosphorylation of Src kinases and SHP2, which play a
      regulatory role in immune functions. Moreover, LILRA6 associated with and
      activated MHC class I, beta2-microglobulin and induced the expression of
      transporters associated with antigen processing but LILRA2 did not. Furthermore,
      both LILRA2 and LILRA6 activated JAK-STAT, NF-kappaB, PI3K/AKT and ERK1/2 MAPK
      signaling pathways and induced Th1-, Th2- and Th17-type cytokines and Toll-like
      receptors. Collectively, this study indicates that LILRA2 and LILRA6 are
      essential for macrophage-mediated immune responses and they have the potential to
      complement the innate and adaptive immune system against pathogens.

PMID- 30208632
TI  - Aerobic Capacity Is Not Associated with Most Cognitive Domains in Patients with
      Multiple Sclerosis-A Cross-Sectional Investigation.
AB  - (1) Background: Cognitive impairment is highly prevalent in multiple sclerosis
      (MS). Staying physically fit may be associated with preservation of cognitive
      performance in persons with MS (pwMS); (2) Objective: To investigate the
      association between aerobic capacity and the cognitive domains of information
      processing, learning and memory, and verbal fluency as well as single and
      composite z-scores of the Brief Repeatable Battery of Neuropsychological tests
      (BRBNT) in pwMS; (3) Methods: All subjects first performed the BRBNT and then a
      maximal oxygen consumption (VO2-max) test on a bicycle ergometer as a measure of
      aerobic capacity. Simple and multiple (adjusting for age, sex, and education
      level) regression analyses were performed to evaluate the relationship between
      aerobic capacity and cognitive performance in different domains. Published
      international norms were used to compute z-scores for each individual and
      composite BRBNT score. Furthermore, cognitive impairment was defined as one or
      more z-scores <=-1.5 standard deviation (SD) of healthy controls; (4) Results:
      Eighty-four subjects were included (44.9 +/- 9 years, 16.3 +/- 2 education years,
      Expanded Disability Status Scale (EDSS): 2.6 +/- 1.4, MS-type (relapsing
      remitting, primary progressive, or secondary progressive): 73/6/5, disease
      duration: 9.9 +/- 7 years, VO2-max: 28.4 +/- 7.0 mL O2/min/kg). No significant
      associations between aerobic capacity and cognitive performance in the individual
      BRBNT tests were found, except that a weak relationship was found between aerobic
      capacity and the composite processing speed z-score (R2 = 0.06, p = 0.02). The
      average global BRBNT z-score (-0.2 +/- 0.66) was not associated with aerobic
      capacity. Comparison of the cognitively impaired group (34.5%) with the
      nonimpaired group (65.5%) showed lower aerobic capacity in the impaired group
      (25.9 +/- 1 vs. 29.7 +/- 1 mLO2/min/kg, p = 0.02); (5) Conclusions: Limited
      support was found for an association between performance in most cognitive
      domains and aerobic capacity in the present MS group with a third of patients
      showing signs of cognitive impairments.

PMID- 30208634
TI  - Experimental Study on Shear Behavior of Steel Fiber Reinforced Concrete Beams
      with High-Strength Reinforcement.
AB  - Many researchers have performed experimental and theoretical studies on the shear
      behavior of steel fiber reinforced concrete (SFRC) beams with conventional
      reinforcement; few studies involve the shear behavior of SFRC beams with high
      strength reinforcement. In this paper, the shear test of eleven beams with high
      strength reinforcement was carried out, including eight SFRC beams and three
      reinforced concrete (RC) beams. The load-deflection curve, concrete strain,
      stirrup strain, diagonal crack width, failure mode and shear bearing capacity of
      the beams were investigated. The test results show that steel fiber increases the
      stiffness, ultimate load and failure deformation of the beams, but the increase
      effect of steel fiber decreases with the increase of stirrup ratio. After the
      diagonal crack appears, steel fiber reduces the concrete strains of the diagonal
      section, stirrup strains and diagonal crack width. In addition, steel fiber
      reduces crack height and increases crack number. Finally, the experimental values
      of the shear capacities were compared with the values calculated by CECS38:2004
      and ACI544.4R, and the equation of shear capacity in CECS38:2004 was modified to
      effectively predict the shear capacities of SFRC beams with high-strength
      reinforcement.

PMID- 30208633
TI  - Long Non-Coding RNAs as New Master Regulators of Resistance to Systemic
      Treatments in Breast Cancer.
AB  - Predicting response to systemic treatments in breast cancer (BC) patients is an
      urgent, yet still unattained health aim. Easily detectable molecules such as long
      non-coding RNAs (lncRNAs) are the ideal biomarkers when they act as master
      regulators of many resistance mechanisms, or of mechanisms that are common to
      more than one treatment. These kinds of markers are pivotal in quasi-personalized
      treatment selection, and consequently, in improvement of outcome prediction. In
      order to provide a better approach to understanding development of disease and
      resistance to treatments, we reviewed current literature searching for lncRNA
      associated systemic BC treatments including endocrine therapies, aromatase
      inhibitors, selective estrogen receptor modulators (SERMs), trastuzumab,
      paclitaxel, docetaxel, 5-fluorouracil (5-FU), anthracyclines, and cisplatin. We
      found that the engagement of lncRNAs in resistance is well described, and that
      lncRNAs such as urotelial carcinoma-associated 1 (UCA1) and regulator of
      reprogramming (ROR) are indeed involved in multiple resistance mechanisms, which
      offers tantalizing perspectives for wide usage of lncRNAs as treatment resistance
      biomarkers. Thus, we propose this work as the foundation for a wide landscape of
      functions and mechanisms that link more lncRNAs to resistance to current and new
      treatments in years of research to come.

PMID- 30208629
TI  - Amino Acids in the Development of Prodrugs.
AB  - Although drugs currently used for the various types of diseases (e.g.,
      antiparasitic, antiviral, antibacterial, etc.) are effective, they present
      several undesirable pharmacological and pharmaceutical properties. Most of the
      drugs have low bioavailability, lack of sensitivity, and do not target only the
      damaged cells, thus also affecting normal cells. Moreover, there is the risk of
      developing resistance against drugs upon chronic treatment. Consequently, their
      potential clinical applications might be limited and therefore, it is mandatory
      to find strategies that improve those properties of therapeutic agents. The
      development of prodrugs using amino acids as moieties has resulted in
      improvements in several properties, namely increased bioavailability, decreased
      toxicity of the parent drug, accurate delivery to target tissues or organs, and
      prevention of fast metabolism. Herein, we provide an overview of models currently
      in use of prodrug design with amino acids. Furthermore, we review the challenges
      related to the permeability of poorly absorbed drugs and transport and deliver on
      target organs.

PMID- 30208636
TI  - Extract of the Blood Circulation-Promoting Recipe-84 Can Protect Rat Retinas by
      Inhibiting the beta-Catenin Signaling Pathway.
AB  - Extract of the Blood Circulation-Promoting Recipe (EBR-84) from the Chinese
      Herbal medicine "Blood Circulation Promoting Recipe" could retard retinopathy
      development. This study investigated whether EBR-84 protects retinas by
      inhibiting the beta-catenin pathway using a rat model of retinopathy and a
      retinal ganglion cell 5 (RGC-5) cell death model. RGC death was induced by either
      N-methyl-d-aspartic acid (NMDA) or TWS119 (an activator of the beta-catenin
      pathway). After the corresponding treatment with EBR-84, RGC death and the
      protein expression levels of beta-catenin, cyclooxygenase-2 (COX-2), and vascular
      endothelial growth factor (VEGF) in rat retinas were examined. beta-Catenin
      accumulated in the retinal ganglion cell layer (GCL) of NMDA-treated rats. EBR-84
      (3.9, 7.8, and 15.6 g/kg) significantly attenuated the NMDA-induced RGC loss
      accompanying the reduction of beta-catenin expression. Moreover, the expression
      levels of COX-2 and VEGF were decreased by EBR-84 in a dose-dependent manner. For
      the TWS119-treated rats, EBR-84 also ameliorated RGC loss and lowered the
      expression levels of beta-catenin, COX-2, and VEGF. In vitro, EBR-84 increased
      the viability of NMDA-treated RGC-5 while decreased beta-catenin expression. In
      conclusion, EBR-84 retarded ratretinopathy, and the beta-catenin signaling
      pathway played an important role during this protective process.

PMID- 30208637
TI  - Amorphous Nanoparticulate Formulation of Sirolimus and Its Tablets.
AB  - Nanocrystallization and amorphization have proven to be two effective strategies
      to improve the bioavailability of water-insoluble drugs. The purpose of our work
      was to develop a nano-formulated tablet of sirolimus (SRL) for enhanced
      dissolution. Amorphous SRL nanocomposites were prepared using anti-solvent
      precipitation via a high-gravity rotating packed bed. Various factors that affect
      particle size and size distribution, such as excipients, rotating speed,
      antisolvent/solvent flow rate, were investigated. Structure, stability and in
      vitro dissolution of the as-prepared SRL were evaluated. Furthermore, the
      nanoparticulated SRL tablet formula was screened to control drug release.
      Importantly, SRL tablets exhibit different dissolution profile by adjusting HPMC
      (hydroxypropyl methyl cellulose) content, which makes them more suitable for
      various formulation developments.

PMID- 30208635
TI  - The Loss of alpha- and beta-Tubulin Proteins Are a Pathological Hallmark of
      Chronic Alcohol Consumption and Natural Brain Ageing.
AB  - Repetitive excessive alcohol intoxication leads to neuronal damage and brain
      shrinkage. We examined cytoskeletal protein expression in human post-mortem
      tissue from Brodmann's area 9 of the prefrontal cortex (PFC). Brain samples from
      44 individuals were divided into equal groups of 11 control, 11 alcoholic, 11 non
      alcoholic suicides, and 11 suicide alcoholics matched for age, sex, and post
      mortem delay. Tissue from alcoholic cohorts displayed significantly reduced
      expression of alpha- and beta-tubulins, and increased levels of acetylated alpha
      tubulin. Protein levels of histone deacetylase-6 (HDAC6), and the microtubule
      associated proteins MAP-2 and MAP-tau were reduced in alcoholic cohorts, although
      for MAPs this was not significant. Tubulin gene expressions increased in
      alcoholic cohorts but not significantly. Brains from rats administered alcohol
      for 4 weeks also displayed significantly reduced tubulin protein levels and
      increased alpha-tubulin acetylation. PFC tissue from control subjects had reduced
      tubulin protein expression that was most notable from the sixth to the eighth
      decade of life. Collectively, loss of neuronal tubulin proteins are a hallmark of
      both chronic alcohol consumption and natural brain ageing. The reduction of
      cytosolic tubulin proteins could contribute to the brain volumetric losses
      reported for alcoholic patients and the elderly.

PMID- 30208638
TI  - Optimization and Application of Electrochemical Transducer for Detection of
      Specific Oligonucleotide Sequence for Mycobacterium tuberculosis.
AB  - In this study, the electropolymerization of 4-hydroxyphenylacetic acid (4-HPA)
      over graphite electrodes (GE) was optimized, aiming its application as a
      functionalized electrochemical platform for oligonucleotides immobilization. It
      was investigated for the number of potential cycles and the scan rate influence
      on the monomer electropolymerization by using cyclic voltammetry technique. It
      was observed that the polymeric film showed a redox response in the region of
      +0.53/+0.38 V and the increase in the number of cycles produces more
      electroactive platforms because of the better electrode coverage. On the other
      hand, the decrease of scan rate produces more electroactive platforms because of
      the occurrence of more organized coupling. Scanning electron microscopy (SEM)
      images showed that the number of potential cycles influences the coverage and
      morphology of the electrodeposited polymeric film. However, the images also
      showed that at different scan rates a more organized material was produced. The
      influence of these optimized polymerization parameters was evaluated both in the
      immobilization of specific oligonucleotides and in the detection of hybridization
      with complementary target. Poly(4-HPA)/GE platform has shown efficient and
      sensitive for oligonucleotides immobilization, as well as for a hybridization
      event with the complementary oligonucleotide in all investigated cases. The
      electrode was modified with 100 cycles at 75 mV/s presented the best responses in
      function of the amplitude at the monitored peak current values for the Methylene
      Blue and Ethidium Bromide intercalators. The construction of the genosensor to
      detect a specific oligonucleotide sequence for the Mycobacterium tuberculosis
      bacillus confirmed the results regarding the poly(4-HPA)/GE platform efficiency
      since it showed excellent sensitivity. The limit of detection and the limit of
      quantification was found to be 0.56 (+/-0.05) MUM and 8.6 (+/-0.7) MUM,
      respectively operating with very low solution volumes (15 uL of probe and 10 uL
      target). The biosensor development was possible with optimization of the probe
      adsorption parameters and target hybridization, which led to an improvement in
      the decrease of the Methylene Blue (MB) reduction signal from 14% to 34%. In
      addition, interference studies showed that the genosensor has satisfactory
      selectivity since the hybridization with a non-specific probe resulted in a
      signal decrease (46% lower) when compared to the specific target.

PMID- 30208639
TI  - Research Progress in Organic Photomultiplication Photodetectors.
AB  - Organic photomultiplication photodetectors have attracted considerable research
      interest due to their extremely high external quantum efficiency and
      corresponding high detectivity. Significant progress has been made in the aspects
      of their structural design and performance improvement in the past few years.
      There are two types of organic photomultiplication photodetectors, which are made
      of organic small molecular compounds and polymers. In this paper, the research
      progress in each type of organic photomultiplication photodetectors based on the
      trap assisted carrier tunneling effect is reviewed in detail. In addition, other
      mechanisms for the photomultiplication processes in organic devices are
      introduced. Finally, the paper is summarized and the prospects of future research
      into organic photomultiplication photodetectors are discussed.

PMID- 30208641
TI  - A Short Review on the Microstructure, Transformation Behavior and Functional
      Properties of NiTi Shape Memory Alloys Fabricated by Selective Laser Melting.
AB  - Due to unique functional and mechanical properties, NiTi shape memory alloys are
      one of the most promising metallic functional materials. However, the poor
      workability limits the extensive utilization of NiTi alloys as components of
      complex shapes. The emerging additive manufacturing techniques provide high
      degrees of freedom to fabricate complex structures. A freeform fabrication of
      complex structures by additive manufacturing combined with the unique functional
      properties (e.g., shape memory effect and superelasticity) provide great
      potential for material and structure design, and thus should lead to numerous
      applications. In this review, the unique microstructure that is generated by
      selective laser melting (SLM) is discussed first. Afterwards, the previously
      reported transformation behavior and mechanical properties of NiTi alloys
      produced under various SLM conditions are summarized.

PMID- 30208642
TI  - Identification of Antiglycative Compounds in Japanese Red Water Pepper (Red Leaf
      Variant of the Persicaria hydropiper Sprout).
AB  - Glycation, the nonenzymatic reaction between proteins and excess blood sugar, is
      implicated in multiple disorders and occurs via the formation and accumulation of
      advanced glycation end products (AGEs). In our previous studies, we demonstrated
      that the red-leaf variant of the Persicaria hydropiper sprout (Japanese red water
      pepper, Benitade) is one of the potent plants that inhibit formation of AGEs. In
      this study, we aimed to identify antiglycative compounds in Benitade. Benitade
      extracts were prepared with hot water, then fractionated by using high
      performance liquid chromatography (HPLC). The antiglycative efficacy of each
      fraction was evaluated by measuring the formation of fluorescent AGEs (Ex 370
      nm/Em 440 nm). Two fractions, which contained peaks at 26.4 min and 31.8 min,
      showed potent antiglycative efficacy. When we hydrolyzed these peaks, they
      shifted to 32.5 and 41.4 min, which are the same retention times as cyanidin and
      quercetin, respectively. Based on thin-layer chromatography, both compounds
      contained galactose. Finally, ultrahigh-performance liquid
      chromatography/quadrupole-time of flight mass spectrometry (UHPLC-QqTOF-MS)
      analyses were performed to determine the structure of those compounds. Overall,
      we identified two glycosides, cyanidin 3-O-galactoside (idaein) and quercetin 3-O
      galactoside (hyperin), as representative antiglycative compounds in Benitade.

PMID- 30208640
TI  - Peptides as Therapeutic Agents for Inflammatory-Related Diseases.
AB  - Inflammation is a physiological mechanism used by organisms to defend themselves
      against infection, restoring homeostasis in damaged tissues. It represents the
      starting point of several chronic diseases such as asthma, skin disorders,
      cancer, cardiovascular syndrome, arthritis, and neurological diseases. An
      increasing number of studies highlight the over-expression of inflammatory
      molecules such as oxidants, cytokines, chemokines, matrix metalloproteinases, and
      transcription factors into damaged tissues. The treatment of inflammatory
      disorders is usually linked to the use of unspecific small molecule drugs that
      can cause undesired side effects. Recently, many efforts are directed to develop
      alternative and more selective anti-inflammatory therapies, several of them imply
      the use of peptides. Indeed, peptides demonstrated as elected lead compounds
      toward several targets for their high specificity as well as recent and
      innovative synthetic strategies. Several endogenous peptides identified during
      inflammatory responses showed anti-inflammatory activities by inhibiting,
      reducing, and/or modulating the expression and activity of mediators. This review
      aims to discuss the potentialities and therapeutic use of peptides as anti
      inflammatory agents in the treatment of different inflammation-related diseases
      and to explore the importance of peptide-based therapies.

PMID- 30208643
TI  - Fecal Volatile Organic Compounds in Preterm Infants Are Influenced by Enteral
      Feeding Composition.
AB  - Fecal volatile organic compound (VOC) analysis has shown great potential as a
      noninvasive diagnostic biomarker for a variety of diseases. Before clinical
      implementation, the factors influencing the outcome of VOC analysis need to be
      assessed. Recent studies found that the sampling conditions can influence the
      outcome of VOC analysis. However, the dietary influences remains unknown,
      especially in (preterm) infants. Therefore, we assessed the effects of feeding
      composition on fecal VOC patterns of preterm infants (born at <30 weeks
      gestation). Two subgroups were defined: (1) daily intake >75% breastmilk (BM)
      feeding and (2) daily intake >75% formula milk (FM) feeding. Fecal samples, which
      were collected at 7, 14 and 21 days postnatally, were analyzed by an electronic
      nose device (Cyranose 320(r)). In total, 30 preterm infants were included (15 FM,
      15 BM). No differences in the fecal VOC patterns were observed at the three
      predefined time-points. Combining the fecal VOC profiles of these time-points
      resulted in a statistically significant difference between the two subgroups
      although this discriminative accuracy was only modest (AUC [95% CI]; p-value;
      sensitivity; and specificity of 0.64 [0.51-0.77]; 0.04; 68%; and 51%,
      respectively). Our results suggest that the influence of enteral feeding on the
      outcome of fecal VOC analysis cannot be ignored in this population. Furthermore,
      in both subgroups, the fecal VOC patterns showed a stable longitudinal course
      within the first month of life.

PMID- 30208646
TI  - A Lightweight Convolutional Neural Network Based on Visual Attention for SAR
      Image Target Classification.
AB  - With the continuous development of the convolutional neural network (CNN) concept
      and other deep learning technologies, target recognition in Synthetic Aperture
      Radar (SAR) images has entered a new stage. At present, shallow CNNs with simple
      structure are mostly applied in SAR image target recognition, even though their
      feature extraction ability is limited to a large extent. What's more, research on
      improving SAR image target recognition efficiency and imbalanced data processing
      is relatively scarce. Thus, a lightweight CNN model for target recognition in SAR
      image is designed in this paper. First, based on visual attention mechanism, the
      channel attention by-pass and spatial attention by-pass are introduced to the
      network to enhance the feature extraction ability. Then, the depthwise separable
      convolution is used to replace the standard convolution to reduce the computation
      cost and heighten the recognition efficiency. Finally, a new weighted distance
      measure loss function is introduced to weaken the adverse effect of data
      imbalance on the recognition accuracy of minority class. A series of recognition
      experiments based on two open data sets of MSTAR and OpenSARShip are implemented.
      Experimental results show that compared with four advanced networks recently
      proposed, our network can greatly diminish the model size and iteration time
      while guaranteeing the recognition accuracy, and it can effectively alleviate the
      adverse effects of data imbalance on recognition results.

PMID- 30208644
TI  - Genetic Imbalances in Argentinean Patients with Congenital Conotruncal Heart
      Defects.
AB  - Congenital conotruncal heart defects (CCHD) are a subset of serious congenital
      heart defects (CHD) of the cardiac outflow tracts or great arteries. Its
      frequency is estimated in 1/1000 live births, accounting for approximately 10-30%
      of all CHD cases. Chromosomal abnormalities and copy number variants (CNVs)
      contribute to the disease risk in patients with syndromic and/or non-syndromic
      forms. Although largely studied in several populations, their frequencies are
      barely reported for Latin American countries. The aim of this study was to
      analyze chromosomal abnormalities, 22q11 deletions, and other genomic imbalances
      in a group of Argentinean patients with CCHD of unknown etiology. A cohort of 219
      patients with isolated CCHD or associated with other major anomalies were
      referred from different provinces of Argentina. Cytogenetic studies, Multiplex
      Ligation-Probe-Amplification (MLPA) and fluorescent in situ hybridization (FISH)
      analysis were performed. No cytogenetic abnormalities were found. 22q11 deletion
      was found in 23.5% of the patients from our cohort, 66% only had CHD with no
      other major anomalies. None of the patients with transposition of the great
      vessels (TGV) carried the 22q11 deletion. Other 4 clinically relevant CNVs were
      also observed: a distal low copy repeat (LCR)D-E 22q11 duplication, and 17p13.3,
      4q35 and TBX1 deletions. In summary, 25.8% of CCHD patients presented imbalances
      associated with the disease.

PMID- 30208647
TI  - Avoiding Void Holes and Collisions with Reliable and Interference-Aware Routing
      in Underwater WSNs.
AB  - Sparse node deployment and dynamic network topology in underwater wireless sensor
      networks (UWSNs) result in void hole problem. In this paper, we present two
      interference-aware routing protocols for UWSNs (Intar: interference-aware
      routing; and Re-Intar: reliable and interference-aware routing). In proposed
      protocols, we use sender based approach to avoid the void hole. The beauty of the
      proposed schemes is that they not only avoid void hole but also reduce the
      probability of collision. The proposed Re-Intar also uses one-hop backward
      transmission at the source node to further improve the packet delivery ratio of
      the network. Simulation results verify the effectiveness of the proposed schemes
      in terms of end-to-end delay, packet delivery ratio and energy consumption.

PMID- 30208645
TI  - Mixed Peptide-Conjugated Chitosan Matrices as Multi-Receptor Targeted Cell
      Adhesive Scaffolds.
AB  - Biomaterials are important for cell and tissue engineering. Chitosan is widely
      used as a scaffold because it is easily modified using its amino groups, can
      easily form a matrix, is stable under physiological conditions, and is inactive
      for cell adhesion. Chitosan is an excellent platform for peptide ligands,
      especially cell adhesive peptides derived from extracellular matrix (ECM)
      proteins. ECM proteins, such as collagen, fibronectin, and laminin, are
      multifunctional and have diverse cell attachment sites. Various cell adhesive
      peptides have been identified from the ECM proteins, and these are useful to
      design functional biomaterials. The cell attachment activity of peptides is
      influenced by the solubility, conformation, and coating efficiency to solid
      materials, whereas immobilization of peptides to a polysaccharide such as
      chitosan avoids these problems. Peptide-chitosan matrices promote various
      biological activities depending on the peptide. When the peptides are immobilized
      to chitosan, the activity of the peptides is significantly enhanced. Further,
      mixed peptide-chitosan matrices, conjugated with more than one peptide on a
      chitosan matrix, interact with multiple cellular receptors and promote specific
      biological responses via receptor cross-talk. Receptor cross-talk is important
      for mimicking the biological activity of ECM and the proteins. The mixed peptide
      chitosan matrix approach is useful to develop biomaterials as a synthetic ECM for
      cell and tissue engineering.

PMID- 30208648
TI  - CNN-Based Multimodal Human Recognition in Surveillance Environments.
AB  - In the current field of human recognition, most of the research being performed
      currently is focused on re-identification of different body images taken by
      several cameras in an outdoor environment. On the other hand, there is almost no
      research being performed on indoor human recognition. Previous research on indoor
      recognition has mainly focused on face recognition because the camera is usually
      closer to a person in an indoor environment than an outdoor environment. However,
      due to the nature of indoor surveillance cameras, which are installed near the
      ceiling and capture images from above in a downward direction, people do not look
      directly at the cameras in most cases. Thus, it is often difficult to capture
      front face images, and when this is the case, facial recognition accuracy is
      greatly reduced. To overcome this problem, we can consider using the face and
      body for human recognition. However, when images are captured by indoor cameras
      rather than outdoor cameras, in many cases only part of the target body is
      included in the camera viewing angle and only part of the body is captured, which
      reduces the accuracy of human recognition. To address all of these problems, this
      paper proposes a multimodal human recognition method that uses both the face and
      body and is based on a deep convolutional neural network (CNN). Specifically, to
      solve the problem of not capturing part of the body, the results of recognizing
      the face and body through separate CNNs of VGG Face-16 and ResNet-50 are combined
      based on the score-level fusion by Weighted Sum rule to improve recognition
      performance. The results of experiments conducted using the custom-made Dongguk
      face and body database (DFB-DB1) and the open ChokePoint database demonstrate
      that the method proposed in this study achieves high recognition accuracy (the
      equal error rates of 1.52% and 0.58%, respectively) in comparison to face or body
      single modality-based recognition and other methods used in previous studies.

PMID- 30208649
TI  - Bidisperse Magnetic Particles Coated with Gelatin and Graphite Oxide:
      Magnetorheology, Dispersion Stability, and the Nanoparticle-Enhancing Effect.
AB  - The magnetorheology and dispersion stability of bidisperse magnetic particles
      (BMP)-based magnetorheological (MR) fluids were improved by applying a novel
      functional coating composed of gelatin and graphite oxide (GO) to the surfaces of
      the micron-sized carbonyl iron (CI) and nanoparticles Fe3O4. Gelatin acted as a
      grafting agent to reduce the aggregation and sedimentation of CI particles and
      prevent nanoparticles Fe3O4 from oxidation. In addition, a dense GO network on
      the surface of gelatin-coated BMP was synthesized by self-assembly to possess a
      better MR performance and redispersibility. The rheological properties of MR
      fluids containing dual-coated BMP were measured by a rotational rheometer under
      the presence of magnetic field and their dispersion stability was examined
      through sedimentation tests. The results showed that CI@Fe3O4@Gelatin@GO
      (CI@Fe3O4@G@GO) particles possessed enhanced MR properties and dispersion
      stability. In addition, the nanoparticle-enhancing effects on the dispersion
      stability of BMP-based MR fluids were investigated using Monte Carlo simulations.

PMID- 30208651
TI  - Effect of Central Longitudinal Dipole Interactions on Chiral Liquid-Crystal
      Phases.
AB  - Monte Carlo simulations of chiral liquid-crystals, represented by a simple coarse
      grained chiral Gay-Berne model, were performed to investigate the effect of
      central longitudinal dipole interactions on phase behavior. A systematic analysis
      of the structural properties and phase behavior of both achiral and chiral
      systems, with dipole interactions, reveals differing effects; strong dipole
      interactions enhance the formation of layered structures; however, chiral
      interactions may prevent the formation of such phases under certain conditions.
      We also observed a short-ranged smectic structure within the cholesteric phases
      with strong dipole interactions. This constitutes possible evidence of presmectic
      ordering and/or the existence of chiral line liquid phases, which have previously
      been observed in X-ray experiments to occur between the smectic twisted grain
      boundary and cholesteric phases. These results provide a systematic understanding
      of how the phase behavior of chiral liquid-crystals changes when alterations are
      made to the strength of dipole interactions.

PMID- 30208650
TI  - The Presence of Cu Facilitates Adsorption of Tetracycline (TC) onto Water
      Hyacinth Roots.
AB  - Batch experiments were conducted to investigate the adsorption characteristics of
      tetracycline (TC), and the interactive effects of copper (Cu) on the adsorption
      of TC onto water hyacinth roots. TC removal efficiency by water hyacinth roots
      was ranging from 58.9% to 84.6%, for virgin TC, 1:1 TC-Cu and 1:2 TC-Cu. The
      Freundlich isotherm model and the pseudo-second-order kinetic model fitted the
      adsorption data well. Thermodynamics parameters DeltaG0 for TC were more negative
      in the TC plus Cu than the TC-only treatments, indicating the spontaneity of TC
      adsorption increased with increasing of Cu concentrations. An elevated
      temperature was associated with increasing adsorption of TC by water hyacinth
      roots. The additions of Cu(II) significantly increased TC adsorption onto water
      hyacinth roots within the pH range 4 to 6, because copper formed a strong metal
      bridge between root surface and TC molecule, facilitating the adsorption of TC by
      roots. However, Cu(II) hindered TC adsorption onto water hyacinth roots on the
      whole at pH range from 6-10, since the stronger electrostatic repulsion and
      formation of CuOH+ and Cu(OH)2. Therefore, the interaction between Cu(II) and TC
      under different environmental conditions should be taken into account to
      understand the environmental behavior, fate, and ecotoxicity of TC.

PMID- 30208653
TI  - Interlaminar Shear Behavior of Laminated Carbon Fiber Reinforced Plastic from
      Microscale Strain Distributions Measured by Sampling Moire Technique.
AB  - In this article, the interlaminar shear behavior of a [+/-45 degrees ]4s
      laminated carbon fiber reinforced plastic (CFRP) specimen is investigated, by
      utilizing microscale strain mapping in a wide field of view. A three-point
      bending device is developed under a laser scanning microscope, and the full-field
      strain distributions, including normal, shear and principal strains on the cross
      section of CFRP, in a three-point bending test, are measured using a developed
      sampling Moire technique. The microscale shear strain concentrations at
      interfaces between each two adjacent layers were successfully detected and found
      to be positive-negative alternately distributed before damage occurrence. The 45
      degrees  layers slipped to the right relative to the -45 degrees  layers,
      visualized from the revised Moire phases, and shear strain distributions of the
      angle-ply CFRP under different loads. The absolute values of the shear strain at
      interfaces gradually rose with the increase of the bending load, and the sudden
      decrease of the shear strain peak value implied the occurrence of interlaminar
      damage. The evolution of the shear strain concentrations is useful in the
      quantitative evaluation of the potential interlaminar shear failure.

PMID- 30208652
TI  - The Role of Heavy Metals in Plant Response to Biotic Stress.
AB  - The present review discusses the impact of heavy metals on the growth of plants
      at different concentrations, paying particular attention to the hormesis effect.
      Within the past decade, study of the hormesis phenomenon has generated
      considerable interest because it was considered not only in the framework of
      plant growth stimulation but also as an adaptive response of plants to a low
      level of stress which in turn can play an important role in their responses to
      other stress factors. In this review, we focused on the defence mechanisms of
      plants as a response to different metal ion doses and during the crosstalk
      between metal ions and biotic stressors such as insects and pathogenic fungi.
      Issues relating to metal ion acquisition and ion homeostasis that may be
      essential for the survival of plants, pathogens and herbivores competing in the
      same environment were highlighted. Besides, the influence of heavy metals on
      insects, especially aphids and pathogenic fungi, was shown. Our intention was
      also to shed light on the relationship between heavy metals deposition in the
      environment and ecological communities formed under a strong selective pressure.

PMID- 30208655
TI  - Multi-Body Interactions in Molecular Docking Program Devised with Key Water
      Molecules in Protein Binding Sites.
AB  - Water molecules play an important role in modeling protein-ligand interactions.
      However, traditional molecular docking methods often ignore the impact of the
      water molecules by removing them without any analysis or keeping them as a static
      part of the proteins or the ligands. Hence, the accuracy of the docking
      simulations will inevitably be damaged. Here, we introduce a multi-body docking
      program which incorporates the fixed or the variable number of the key water
      molecules in protein-ligand docking simulations. The program employed NSGA II, a
      multi-objective optimization algorithm, to identify the binding poses of the
      ligand and the key water molecules for a protein. To this end, a force-field
      based hydration-specific scoring function was designed to favor estimate the
      binding affinity considering the key water molecules. The program was evaluated
      in aspects of the docking accuracy, cross-docking accuracy, and screening
      efficiency. When the numbers of the key water molecules were treated as fixed
      length optimization variables, the docking accuracy of the multi-body docking
      program achieved a success rate of 80.58% for the best RMSD values for the
      recruit of the ligands smaller than 2.0 A. The cross-docking accuracy was
      investigated on the presence and absence of the key water molecules by four
      protein targets. The screening efficiency was assessed against those protein
      targets. Results indicated that the proposed multi-body docking program was with
      good performance compared with the other programs. On the other side, when the
      numbers of the key water molecules were treated as variable-length optimization
      variables, the program obtained comparative performance under the same three
      evaluation criterions. These results indicated that the multi-body docking with
      the variable numbers of the water molecules was also efficient. Above all, the
      multi-body docking program developed in this study was capable of dealing with
      the problem of the water molecules that explicitly participating in protein
      ligand binding.

PMID- 30208654
TI  - Correction of a Splicing Mutation Affecting an Unverricht-Lundborg Disease
      Patient by Antisense Therapy.
AB  - Unverricht-Lundborg disease (ULD) is a common form of progressive myoclonic
      epilepsy caused by mutations in the cystatin B gene (CSTB) that encodes an
      inhibitor of several lysosomal cathepsins. Presently, only pharmacological
      treatment and psychosocial support are available for ULD patients. To overcome
      the pathogenic effect of the ULD splicing mutation c.66G>A (exon 1), we
      investigated whether an antisense oligonucleotide therapeutic strategy could
      correct the defect in patient cells. A specific locked nucleic acid (LNA)
      antisense oligonucleotide was designed to block a cryptic 5'ss in intron 1.
      Overall, this approach allowed the restoration of the normal splicing pattern.
      Furthermore, the recovery was both sequence and dose-specific. In general, this
      work provides a proof of principle on the correction of a CSTB gene defect
      causing ULD through a mutation-specific antisense therapy. It adds evidence to
      the feasibility of this approach, joining the many studies that are paving the
      way for translating antisense technology into the clinical practice. The insights
      detailed herein make mutation-based therapy a clear candidate for personalized
      treatment of ULD patients, encouraging similar investigations into other genetic
      diseases.

PMID- 30208656
TI  - CRISPR/Cas9-Mediated Multiplex Genome Editing of the BnWRKY11 and BnWRKY70 Genes
      in Brassica napus L.
AB  - Targeted genome editing is a desirable means of basic science and crop
      improvement. The clustered, regularly interspaced, palindromic repeat
      (CRISPR)/Cas9 (CRISPR-associated 9) system is currently the simplest and most
      commonly used system in targeted genomic editing in plants. Single and multiplex
      genome editing in plants can be achieved under this system. In Arabidopsis,
      AtWRKY11 and AtWRKY70 genes were involved in JA- and SA-induced resistance to
      pathogens, in rapeseed (Brassica napus L.), BnWRKY11 and BnWRKY70 genes were
      found to be differently expressed after inoculated with the pathogenic fungus,
      Sclerotinia sclerotiorum (Lib.) de Bary. In this study, two Cas9/sgRNA constructs
      targeting two copies of BnWRKY11 and four copies of BnWRKY70 were designed to
      generate BnWRKY11 and BnWRKY70 mutants respectively. As a result, twenty-two
      BnWRKY11 and eight BnWRKY70 independent transformants (T0) were obtained, with
      the mutation ratios of 54.5% (12/22) and 50% (4/8) in BnWRKY11 and BnWRKY70
      transformants respectively. Eight and two plants with two copies of mutated
      BnWRKY11 and BnWRKY70 were obtained respectively. In T1 generation of each plant
      examined, new mutations on target genes were detected with high efficiency. The
      vast majority of BnWRKY70 mutants showed editing in three copies of BnWRKY70 in
      examined T1 plants. BnWRKY70 mutants exhibited enhanced resistance to
      Sclerotinia, while BnWRKY11 mutants showed no significant difference in
      Sclerotinia resistance when compared to non-transgenic plants. In addition,
      plants that overexpressed BnWRKY70 showed increased sensitivity when compared to
      non-transgenic plants. Altogether, our results demonstrated that BnWRKY70 may
      function as a regulating factor to negatively control the Sclerotinia resistance
      and CRISPR/Cas9 system could be used to generate germplasm in B. napus with high
      resistance against Sclerotinia.

PMID- 30208657
TI  - Impact of X-ray Exposure on the Proliferation and Differentiation of Human Pre
      Adipocytes.
AB  - Radiotherapy is a widely used treatment option for cancer patients as well as for
      patients with musculoskeletal disorders. Adipocytes, the dominant cell type of
      adipose tissue, are known to constitute an active part of the tumor
      microenvironment. Moreover, adipocytes support inflammatory processes and
      cartilage degradation in chronic inflammatory diseases, i.e., rheumatoid and
      osteoarthritis. Since the production of inflammatory factors is linked to their
      differentiation stages, we set out to explore the radiation response of pre
      adipocytes that may influence their inflammatory potential and differentiation
      capacity. This is the first study investigating the effects of X-ray irradiation
      on the proliferation and differentiation capacity of human primary pre
      adipocytes, in comparison to Simpson-Golabi-Behmel Syndrome (SGBS) pre
      adipocytes, an often-used in vitro model of human primary pre-adipocytes. Our
      results demonstrate a dose-dependent reduction of the proliferation capacity for
      both cell strains, whereas the potential for differentiation was mostly
      unaffected by irradiation. The expression of markers of adipogenic development,
      such as transcription factors (PPARgamma, C/EBPalpha and C/EBPbeta), as well as
      the release of adipokines (visfatin, adiponectin and leptin) were not
      significantly changed upon irradiation. However, after irradiation with high X
      ray doses, an increased lipid accumulation was observed, which suggests a
      radiation-induced response of adipocytes related to inflammation. Our results
      indicate that pre-adipocytes are radio-resistant, and it remains to be elucidated
      whether this holds true for the overall inflammatory response of adipocytes upon
      irradiation.

PMID- 30208659
TI  - Effect on Nail Structure and Transungual Permeability of the Ethanol and
      Poloxamer Ratio from Cyclodextrin-Soluble Polypseudorotaxanes Based Nail Lacquer.
AB  - Aqueous-based nail lacquers have shown potential in promoting the diffusion of
      drugs into the nail. In our laboratory, we have recently developed a transungual
      delivery system based on an aqueous dispersion of cyclodextrin-poloxamer soluble
      polypseudorotaxanes, supramolecular host-guest assemblies that improves the drug
      permeation into the nail. However, the high-water content and the rheological and
      adhesive properties of this lacquer negatively affect properties that play a
      fundamental role in the patients' acceptance such as stickiness, nail film
      formation or drying rate, properties. In this work, we have optimized the
      composition of these lacquers to improve these properties whilst maintaining good
      drug permeation profiles. Incorporating ethanol into the vehicle and reducing the
      proportion of Poloxamer 407 (PL), provided a good strategy. The use of hydro
      ethanolic mixtures (>50% ethanol) and the reduction of the poloxamer
      concentration significantly improved the lacquer drying speed by reducing the
      stickiness and promoting film formation on the nail surface. Additionally, in a
      surprising way, the use of hydro-ethanolic vehicles further enhanced the
      permeation of ciclopirox olamine and clobetasol propionate, used for the
      treatment of onychomycosis and nail psoriasis respectively, into the nail and
      hooves.

PMID- 30208658
TI  - Sintering Pmperature-Dependence on Radiopacity of Bi(2-x) ZrxO(3+x/2) Powders
      Prepared by Sol-Gel Process.
AB  - Bismuth oxide (Bi2O3) is an effective additive used to enhance radiography
      resolution for dental materials. However, there are potential concerns regarding
      its biocompatibility and connection to tissue discoloration. In the present
      study, we modified the radiopacity properties of Bi2O3 with zirconium oxide
      (ZrO2) using a sol-gel process and investigated the composition, as well as the
      effects of heat treatment temperature using Thermogravimetry analysis (TGA),
      differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy
      (FT-IR), transmission electron microscopy (TEM), and X-ray diffraction (XRD). The
      harvested Bi2-xZrxO3+x/2 particles showed that the dominant phase transferred
      from alpha-Bi2O3 to beta-Bi7.38Zr0.62O12.31 after a heat treatment of over 750 
      degrees C for 2 h. As the x values of Bi2-xZrxO3+x/2 increased from 0.2 to 1.0,
      more zirconium oxide precipitated onto the particle surface, thus enhancing the
      surface roughness of particles. For sol-gel Bi1.8Zr0.2O3.1 powders (x = 0.2), the
      radiopacity values became 4.90 +/- 0.23 and 5.83 +/- 0.22 mmAl after a heat
      treatment of 500  degrees C and 750  degrees C, respectively.

PMID- 30208660
TI  - Statistic Experience Based Adaptive One-Shot Detector (EAO) for Camera Sensing
      System.
AB  - Object detection in a camera sensing system has been addressed by researchers in
      the field of image processing. Highly-developed techniques provide researchers
      with great opportunities to recognize objects by applying different algorithms.
      This paper proposes an object recognition model, named Statistic Experience-based
      Adaptive One-shot Detector (EAO), based on convolutional neural network. The
      proposed model makes use of spectral clustering to make detection dataset,
      generates prior boxes for object bounding and assigns prior boxes based on multi
      resolution. The model is constructed and trained for improving the detection
      precision and the processing speed. Experiments are conducted on classical images
      datasets while the results demonstrate the superiority of EAO in terms of
      effectiveness and efficiency. Working performance of the EAO is verified by
      comparing it to several state-of-the-art approaches, which makes it a promising
      method for the development of the camera sensing technique.

PMID- 30208661
TI  - Heat-Induced Discoloration of Chromophore Structures in Eucalyptus Lignin.
AB  - The color changes corresponding to chromophore structures in lignin caused by
      exposure of Eucalyptus (Eucalyptus grandis and E. urophylla) to heat were
      investigated. Eucalyptus wood powders were heat treated under saturated steam
      atmospheres for 10 h at 110  degrees C, 130  degrees C and 150  degrees C. The
      lignin was isolated before and after heat treatment. The physicochemical
      properties of the lignin and changes in chromophore structures during heat
      treatment was evaluated through wet chemical analysis, Fourier transform infrared
      spectroscopy (FTIR), diffuse reflectance ultraviolet-visible spectroscopy (DRUV
      Vis), gel permeation chromatography (GPC), X-ray photoelectron spectroscopy (XPS)
      and 13C Cross polarization magic angle spinning nuclear magnetic resonance (13C
      CPMAS NMR). Wood color darkened and reddened with the increase in pressure and
      temperature. Depolymerization and dehydration reactions occurred via
      demethoxylation with heat treatment in saturated steam at 110  degrees C or 130 
      degrees C. Lignin condensed to form insoluble compounds after heat treatment in
      saturated steam at 150  degrees C. G units increased and S units decreased
      through demethylation during heat treatment, as revealed by FTIR and 13C-NMR
      analysis.

PMID- 30208662
TI  - Multi-Index Evaluation for Flood Disaster from Sustainable Perspective: A Case
      Study of Xinjiang in China.
AB  - The floods have undermined the sustainable construction of cities because of
      their sudden and destruction. To reduce the losses caused by floods, it is
      necessary to make a reasonable evaluation for historical floods and provide
      scientific guidance for future precaution. Previous research mainly used
      subjective/objective weights or barely made static analysis without considering
      the uncertainty and ambiguity of floods. Therefore, this study proposed a
      variable fuzzy recognition model, based on combined weights, to evaluate floods,
      including the determination of index weights and the choice of evaluation model.
      To make the index weights reflect both subjective experience and objective data,
      the combined weights were proposed and calculated based on the principle of
      minimum identification information. Then, the relative membership degree matrix
      and evaluation results can be worked out by the variable fuzzy recognition model.
      Conclusions indicated that the combined weights were more convincing than simply
      subjective or objective weights. Moreover, the variable fuzzy recognition model,
      by changing model parameters, got stable evaluation results of the sample data.
      Therefore, the model can improve the credibility of evaluation and the
      conclusions can provide reasonable suggestions for management departments.

PMID- 30208665
TI  - Pixel-Wise Crack Detection Using Deep Local Pattern Predictor for Robot
      Application.
AB  - Robotic vision-based crack detection in concrete bridges is an essential task to
      preserve these assets and their safety. The conventional human visual inspection
      method is time consuming and cost inefficient. In this paper, we propose a robust
      algorithm to detect cracks in a pixel-wise manner from real concrete surface
      images. In practice, crack detection remains challenging in the following
      aspects: (1) detection performance is disturbed by noises and clutters of
      environment; and (2) the requirement of high pixel-wise accuracy is difficult to
      obtain. To address these limitations, three steps are considered in the proposed
      scheme. First, a local pattern predictor (LPP) is constructed using convolutional
      neural networks (CNN), which can extract discriminative features of images.
      Second, each pixel is efficiently classified into crack categories or non-crack
      categories by LPP, using as context a patch centered on the pixel. Lastly, the
      output of CNN-i.e., confidence map-is post-processed to obtain the crack areas.
      We evaluate the proposed algorithm on samples captured from several concrete
      bridges. The experimental results demonstrate the good performance of the
      proposed method.

PMID- 30208663
TI  - Comparison of Cytomorphometry and Early Cell Response of Human Gingival
      Fibroblast (HGFs) between Zirconium and New Zirconia-Reinforced Lithium Silicate
      Ceramics (ZLS).
AB  - New zirconia-reinforced lithium silicate ceramics (ZLS) could be a viable
      alternative to zirconium (Y-TZP) in the manufacture of implantological abutments
      especially in aesthetic cases-due to its good mechanical, optical, and
      biocompatibility properties. Although there are several studies on the ZLS
      mechanical properties, there are no studies regarding proliferation, spreading,
      or cytomorphometry. We designed the present study which compares the surface,
      cellular proliferation, and cellular morphology between Y-TZP (Vita YZ(r) T [Vita
      Zahnfabrik (Postfach, Germany)]) and ZLS (Celtra(r) Duo [Degudent (Hanau
      Wolfgang, Germany)]). The surface characterization was performed with energy
      dispersive spectroscopy (EDS), scanning electron microscopy (SEM), and optical
      profilometry. Human gingival fibroblasts (HGFs) were subsequently cultured on
      both materials and early cellular response and cell morphology were compared
      through nuclear and cytoskeletal measurement parameters using confocal
      microscopy. The results showed greater proliferation and spreading on the surface
      of Y-TZP. This could indicate that Y-TZP continues to be a gold standard in terms
      of transgingival implant material: Nevertheless, more in vitro and in vivo
      research is necessary to confirm the results obtained in this study.

PMID- 30208667
TI  - Thai Fermented Foods as a Versatile Source of Bioactive Microorganisms-A
      Comprehensive Review.
AB  - Fermented foods are known for several health benefits, and they are generally
      used among the Asian people. Microorganisms involved in the fermentation process
      are most responsible for the final quality of the food. Traditional fermented
      (spontaneous fermentation) foods are a versatile source of bioactive molecules
      and bioactive microbes. Several reports are available regarding the isolation and
      characterization of potent strains from traditional fermented foods. A collection
      of information for easy literature analysis of bioactive microbes derived from
      Thai fermented food is not yet available. The current manuscript compiled
      information on bioactive (antimicrobial- and enzyme-producing probiotic) microbes
      isolated from naturally fermented Thai foods.

PMID- 30208668
TI  - The development of amphids and amphidial glands in adult Syngamus trachea
      (Nematoda: Syngamidae).
AB  - Nematode amphids are a pair of lateral cephalic sense organs, each comprising a
      group of sensory endings terminating in a cuticle-lined pit. In Syngamus trachea,
      a parasite of birds, each amphid is surrounded by two non-nervous supporting
      elements, a large gland cell basally and a smaller supporting cell anteriorly.
      The amphidial glands display high levels of secretory activity from five to six
      days postinfection. Secretory material is discharged through the lumen of the
      sense organ onto host tissue. The ultrastructure of amphids and amphidial glands
      has been investigated in newly moulted, immature and mature adults to trace the
      development of glandular activity and its effect on amphid-amphidial gland
      relationships. In newly moulted adults, the glands have very low levels of
      secretory activity and appear to act only as supporting cells to the amphids. As
      secretory activity increases, the gland cell membrane surrounding the sensory
      endings is elaborated into a reticulum which probably forms the secretory
      surface. In mature adults the amphid pit is swollen and filled with secretion;
      the sensory endings are relegated to the periphery of the lumen. It is suggested
      that amphidial glands develop from typical supporting cells, but acquire a new
      role possibly associated with parasite attachment.

PMID- 30208669
TI  - The structure of the canary's incubation patch.
AB  - The gross morphology, histology and ultrastructure of the canary's incubation
      patch and the ventral apterium from which it arises are described. The apterium
      is vascularized by pectoral, external mammary, incubation, and prepubic arteries.
      It is innervated by cutaneous branches of spinal nerves. It has a surface area of
      6 cm2 . Its epidermis is a stratified squamous epithelium with basal,
      intermediate, transitional and cornified layers. Cells in the stratum
      germinativum contain a normal array of organelles, but are characterized by
      tonofilaments, desmosomes and interdigitating surfaces. Cellular organelles
      disappear in the stratum transitivum and are replaced by large vacuoles and
      keratohyalin bands. Nonmyelinated nerve fibers are abundant in the stratum
      germinativum. The dermis consists of (1) an avascular layer of dense collagen
      subjacent to the epidermis and containing many nonmyelinated nerves, and (2) an
      underlying layer of areolar connective tissue containing blood vessels, lamellar
      corpuscles and nerves. A layer of coarse elastic fibers, reinforced by collagen
      and smooth muscle, separates the dermis from subcutaneous tissue. In contrast to
      the ventral apterium, the incubation patch is featherless and visibly
      hypervascular and edematous. Its epidermis is both hypertrophic and hyperplastic.
      Large spaces separate cells in the stratum germinativum. The visible
      hypervascularity is due to hyperemia and increased number and size of blood
      vessels in the dermis. Visible edema is due to the accumulation of fluid
      interstitially. Although no histological differences exist among various regions
      of the ventral apterium, such differences are present in the incubation patch.

PMID- 30208666
TI  - The Change of Self-Rated Health According to Working Hours for Two Years by
      Gender.
AB  - OBJECTIVE: The aim of this study was to confirm the association between working
      hours and self-rated health, and to find the degree of changes in health level by
      working hours according to gender. METHODS: This study was based on the 929
      workers (571 men and 358 women) from the Korean Labor and Income Panel Study
      during 2004-2006. To minimize the healthy worker effects, the study subjects
      included only those who did not have any chronic diseases, and who answered their
      health status as "moderate" or above in the baseline. Logistic regression
      analysis was used to confirm the associations between working hours and self
      rated health. RESULTS: In men, working hours per week of 47-52 h, 53-68 h, and
      >68 h were associated with 1.2, 1.3, and 1.1 times increases, respectively, in
      the odds ratio on worsened self-rated health, compared with the reference group
      (40-46 h). On the other hand, the risks were 1.0, 2.2, and 2.6 times increases in
      women. However, the results were different according to gender in the group with
      less than 40 h. The men with less than 40 h had a 0.9 times odds ratio on
      worsened self-rated health. For the women with less than 40 h, the odds ratio on
      self-rated health was 5.4 times higher than the reference group. CONCLUSIONS:
      Working more than 52 h per week had a negative effect on health, regardless of
      gender. However, in the group with less than 40 h, the negative association
      between working hours and self-rated health were shown only in women. Health
      outcomes due to working hours may differ by gender. Therefore, further studies
      are needed to explore the causes of these results.

PMID- 30208670
TI  - The mouthparts of female Corethrella brakeleyi and C. wirthi (Diptera:
      Chaoboridae).
AB  - The mouthparts of female Corethrella brakeleyi and C. wirthi were studied using
      light and electron microscopy. Mandibles, hypopharynx and labium are highly
      sclerotized and are modified for obtaining blood meals. All structures were
      larger in C. brakeleyi than in C. wirthi except mandibular and hypopharyngeal
      teeth; these were smaller and more numerous in C. brakeleyi. The labium of both
      species terminates in peg-like structures which are similar to those reported
      from several genera of mosquitoes. Sensillae on the second segment of the
      maxillary palps appear to be identical to those described in both biting and
      nonbiting male and female blackflies.

PMID- 30208671
TI  - The fine structure of blood follicles in the earthworm genera Amynthas and
      Lumbricus (Annelida: Oligochaeta).
AB  - Blood follicles of the earthworm Amynthas are hemoglobin-containing, sac-like
      dilatations of blood vessels which connect to the general circulation. Grape-like
      clusters of follicles are found posterior to the pharynx, among tufts of
      micronephridia, and single follicles are located among cells of the pharyngeal
      gland. In Lumbricus, follicles take the form of simple swellings and irregular
      shaped diverticula of nephridial capillaries. The fundamental structure of the
      wall of follicles and of vessels in both genera is the same and consists of two
      layers: an extracellular vascular lamina and an outer (coelomic) covering of
      smooth muscle-like myoperithelial cells. Hemocytes may be free and circulating or
      they may facultatively attach to the vascular lamina as littoral cells,
      constituting an incomplete endothelium-like surface. Hemocytes that appear to be
      in the process of attaching or detaching are rounded, while adherent cells are
      flattened and elongate. Free and littoral hemocytes actively endocytose packets
      of circulating extracellular hemoglobin. Hemocytes within follicles possess
      radiating cell processes which also endocytose hemoglobin. Although these cells
      were presumed to secrete hemoglobin, staining with 3,3'-diaminobenzidine confirms
      the presence of hemoglobin only within pinosomes and not within protein
      synthesizing or packaging organelles. The presence of hemosiderin-like bodies
      suggests that follicular hemocytes catabolize hemoglobin. Blood follicles
      apparently provide a means of significantly increasing cell-surface area for
      hemoglobin processing, without substantially increasing the volume and pumping
      load of the circulatory system.

PMID- 30208672
TI  - The morphology of the central nervous system of the barnacle, Semibalanus
      cariosus (Pallas).
AB  - The central nervous system of the sessile barnacle, Semibalanus cariosus
      (Pallas), has been studied with the particular aim of determining the locations
      of neuron somata in relation to peripheral nerves. This was accomplished by
      tracing peripheral nerves using dissection and methylene blue staining
      techniques, histological methods, and by permitting cobaltous chloride to diffuse
      via axons into ganglia ("backfilling"). The neuron maps resulting from the study
      reveal some well-defined sub-systems, a considerable degree of functional
      clumping of neuron somata, and some unexpected projections of neurons in the CNS.
      Neurophysiological studies based on these findings are in progress.

PMID- 30208664
TI  - Phenolic Compounds in Honey and Their Associated Health Benefits: A Review.
AB  - Honey is a natural substance appreciated for its therapeutic abilities since
      ancient times. Its content in flavonoids and phenolic acids plays a key role on
      human health, thanks to the high antioxidant and anti-inflammatory properties
      that they exert. Honey possesses antimicrobial capacity and anticancer activity
      against different types of tumors, acting on different molecular pathways that
      are involved on cellular proliferation. In addition, an antidiabetic activity has
      also been highlighted, with the reduction of glucose, fructosamine, and
      glycosylated hemoglobin serum concentration. Honey exerts also a protective
      effect in the cardiovascular system, where it mainly prevents the oxidation of
      low-density lipoproteins, in the nervous system, in the respiratory system
      against asthma and bacterial infections, and in the gastrointestinal system. A
      beneficial effect of honey can also be demonstrated in athletes. The purpose of
      this review is to summarize and update the current information regarding the role
      of honey in health and diseases.

PMID- 30208673
TI  - The telotrophic-meroistic ovary of megaloptera. I. The ontogenetic development.
AB  - Sialis flavilatera L. (Sialidae, Megaloptera) has telotrophic-meroistic
      ovarioles. The germ cells of the tropharium are organized into two distinct
      tissues, the central syncytium and the germ cell tapetum. The central syncytium
      consists of nurse cell nuclei embedded in a common cytoplasm which is rich in
      ribosomes and mitochondria. Cell membranes are totally absent. The germ cell
      tapetum surrounds the syncytium and consists of a monolayer of cells, each of
      which is connected with the central syncytium by an intercellular bridge. The
      oocytes differentiate from basal tapetum cells by previtellogenic growth. Their
      nutritive cords remain connected to the central syncytium by the intercellular
      bridge. Ovariole development starts soon after hatching with the immigration of
      germ cells into the ovariole-anlagen and is finished during pupal stages 23
      months later. In apical regions of each tropharium, mitoses occur throughout
      larval life. The descendants enter the prophase of meiosis which lasts until pre
      vitellogenesis; thus, a differential gradient of position and time is
      established. About 12 months after hatching, the central syncytium arises at the
      base of the tropharium from a membrane labyrinth in which intercellular bridges
      are entangled. Evidence is presented that endopolyploidization does not occur
      during germ cell differentiation. Finally, the results are compared with those
      found in Hemiptera and polyphage Coleoptera. The great diversities are
      interpreted as an indication for a polyphyletic origin of the telotrophic ovary.

PMID- 30208674
TI  - The intranuclear helices of Euplotes: Their substructure, localization, and
      apparent migration to the cytoplasm.
AB  - Study of the fine structure of the macronucleus in Euplotes eurystomus, a ciliate
      protozoon, during various stages of the cell division cycle has yielded new
      information about intranuclear helices. They are frequently observed at the
      periphery of chromatin bodies or next to the nuclear envelope, and they appear to
      be a constituent of nucleoli. The fibril that forms a helix is about 11-15 nm
      thick, and torus profiles of helices cut in cross section are about 35 nm in
      diameter. In substructure the helix is composed of a thin strand 3-5 nm thick
      which is coiled to form the 11-15 nm fibril; so the helix is a super-coiled
      structure. The intranuclear helices are present in the macronucleus throughout
      the cell cycle. They do not show obvious changes of relative abundance nor
      changes of relative localization in the nucleus, with one exception: they were
      never observed in the diffuse zone of replication bands. Evidence is presented
      indicating that nuclear helices migrate to the cytoplasm through nuclear pores.
      Although the chemical composition of the Euplotes intranuclear helices is
      unknown, information in the literature on similar helices in Amoeba indicates
      that they contain RNA and not DNA. The observations on Euplotes helices are
      consistent with a concept of "packaged" RNA for transport to the cytoplasm.

PMID- 30208675
TI  - The structure and distribution of external sense organs in newly hatched and
      mature earthworms.
AB  - Fully mature adult Eisenia foetida sensory buds are abundant on the prostomium
      and the first segment. In subsequent segments they are restricted to the anterior
      half where they form a single row aligned with the setae and encircling the worm.
      In the more posterior regions of the worm the buds are widely separated and
      fewer. The surface of each bud is a raised circular or oval area from which 15 to
      100 so-called sensory hairs arise, being cylindrical and apparently flexible. The
      number of these projections decreases toward the posterior end of the worm. In
      worms newly emerged from egg cocoons, the general pattern of distribution and
      external form of sensory buds resembles that of adults, but the buds are much
      fewer and smaller than in adults. Although these worms emerge with their
      definitive adult number of segments, new buds and additional sensory projections
      are formed during post hatching development.

PMID- 30208676
TI  - The morphology of the sex pheromone gland in Drosophila grimshawi.
AB  - The morphology of a sex pheromone-producing gland found in the abdomen of
      Drosophila grimshawi males was studied by light and electron microscopy. This
      gland, consisting of two intra-anal lobes, contains cells that resemble those of
      other insect pheromone glands. However, in contrast to many other insect
      pheromone glands that release pheromone through the cuticle, cells of the intra
      anal lobes secrete into a canaliculi-duct system that empties into the anal
      region. The liquid secretory product flows along the surface of the intra-anal
      lobes and is brushed onto the substrate by fingerlike projections on the lobes'
      surfaces.

PMID- 30208677
TI  - The extensor assembly in two species of opossum, Philander opossum and Didelphis
      marsupialis.
AB  - In considering primate and hominoid phylogeny, the fundamental position assigned
      to opossums is explained partially by the characteristic morphology of their
      hands and feet. One of the main functional features of the human hand is the
      ability to make a stabilized arch of the finger. Because the extensor assembly
      plays a key role in establishing an arched finger, the extensor systems of the
      digits of both the hands and feet were studied in two species of opossum,
      Philander opossum and Didelphis marsupialis. In the foot, two extensor tendons
      join in each toe to form one tendinous plate, which inserts onto the base of the
      second phalanx. Lumbricals join this plate along the tibial side, and interosseus
      insertions are found, although a true interosseus wing is lacking. At the
      proximal interphalangeal level, a terminal tendon takes its origin from this
      tendinous plate. This terminal tendon is oval in cross-section and contains
      elastic structures. Oblique bands arise from this terminal tendon and run
      proximally along the proximal interphalangeal joint inserting onto the base of
      the first phalanx. There are elastic structures in the flexor tendon on the
      dorsal side near its site of insertion. In the hand, the main extensor tendons
      are arranged differently and the interossei contribute substantially to the
      extensor assembly. Otherwise, the extensor assembly of the hands and feet are
      quite similar. The function of the so-called paratendinous intravaginal flexors
      is discussed as are evolutionary aspects of the extensor assembly.

PMID- 30208678
TI  - Complete Mesocolic Excision With Central Vascular Ligation for the Treatment of
      Patients With Colon Cancer.

PMID- 30208680
TI  - Obstructive Ileocolitis in Patients With Obstructed Colorectal Cancer - A Matched
      Case Control Study.
AB  - PURPOSE: Obstructive ileocolitis is an ulcero-inflammatory condition which
      typically occurs in the ileum or colon proximal to an obstructing colorectal
      lesion. If left unresolved, it often leads to intestinal perforation. We present
      a matched case control study of patients with obstructive ileocolitis caused by
      colorectal cancer to determine if any factors can predict this condition.
      METHODS: This is a retrospective review of 21 patients with obstructive
      colorectal cancer and histologically proven obstructive ileocolitis from 2005 to
      2015 matched for age and sex with 21 controls with obstructing colorectal cancer
      without obstructive ileocolitis. RESULTS: The 21 patients with obstructive
      ileocolitis had a median age of 71 years (range, 52-86 years). The most common
      presenting symptom was abdominal pain (n = 16, 76.2%), followed by
      vomiting/nausea (n = 14, 66.7%) and abdominal distension (n = 12, 57.1%).
      Interestingly, the radiological feature of pneumatosis intestinalis was noted in
      only 1 case. No significant differences were observed in baseline comorbidities,
      clinical presentations, or tumor characteristics between the 2 groups. Patients
      with obstructive ileocolitis were found to have a significantly higher total
      leucocyte count (17.1 +/- 9.4*109/L vs. 12.0 +/- 6.8*109/L, P = 0.016), lower
      pCO2 (32.3 +/- 8.2 mmHg vs. 34.8 +/- 4.9 mmHg, P = 0.013), lower HCO3 (18.8 +/-
      4.5 mmol/L vs. 23.6 +/- 2.7 mmol/L, P < 0.001), lower base excess (-6.53 +/- 5.32
      mmol/L vs. -0.57 +/- 2.99 mmol/L, P < 0.001) and higher serum lactate levels
      (3.14 +/- 2.19 mmol/L vs. 1.19 +/- 0.91 mmol/L, P = 0.007) compared to controls.
      No radiological features were predictive of obstructive ileocolitis. CONCLUSION:
      Patients with obstructive ileocolitis tend to present with metabolic acidosis
      with respiratory compensation, raised lactate, and worse leucocytosis.
      Radiological features are not useful for predicting this condition.

PMID- 30208679
TI  - Intersphincteric Resection for Patients With Low-Lying Rectal Cancer: Oncological
      and Functional Outcomes.
AB  - The aim of this review is to evaluate the outcomes after an intersphincteric
      resection (ISR) for patients with low-lying rectal cancer. Reports published in
      the literature regarding surgical, oncological, and functional outcomes of an ISR
      were reviewed. The morbidity after an ISR was 7.7%-32%, and anastomotic leakage
      was the most common adverse event. Local recurrence rates ranged from 0% to 12%,
      5-year overall survival rates ranged from 62% to 92%, and rates of major
      incontinence ranged from 0% to 25.8% after an ISR. An ISR is a safe procedure for
      sphincter-saving rectal surgery in patients with very low rectal cancer; it does
      not compromise the oncological outcomes of the resection and is a valuable
      alternative to an abdominoperineal resection. While the functional outcomes after
      an ISR were found to be acceptable, the long-term functional outcome and quality
      of life still require careful investigation. ISRs have been performed with
      surgical and oncologic safety on patients with low-lying rectal cancer. However,
      patients must be selected very carefully for an ISR, considering the associated
      functional derangement and the limited extent of the resection.

PMID- 30208681
TI  - Complete Mesocolic Excision With Central Vascular Ligation in Comparison With
      Conventional Surgery for Patients With Colon Cancer - The Experiences at Two
      Centers.
AB  - PURPOSE: Revolutions have occurred over the last 3 decades in the management of
      patients with colorectal cancer. Most advances were in rectal cancer surgery,
      especially after the introduction of the total mesorectal excision (TME) by
      Heald. However, no parallel advances regarding colon cancer surgeries have
      occurred. In 2009, Hohenberger introduced a new concept trying to translate the
      survival advantages of TME to patients with colon cancer. This relatively new
      concept of a complete mesocolic excision (CME) with central vascular ligation
      (CVL) in the management of patients with colon cancer represents an evolution in
      operative technique. We performed a comparative study between CME with CVL and
      conventional surgery for patients with colon cancer at Italian and Egyptian
      cancer centers, considering surgical quality and clinical outcome. METHODS:
      Seventy-nine Egyptian patients underwent conventional surgery (non-CME group)
      while 52 Italian patients underwent CME with sharp dissection between the
      embryological planes and CVL of the supplying vessels (CME group). RESULTS:
      Significantly better results were observed in terms of lymph node yield (CME
      group: 22.5 vs. non-CME group: 12; P < 0.0001) and lymph node ratio (CME group:
      0.03 vs. non-CME group: 0.22; P < 0.0001). Regarding surgical morbidity, no
      significant difference was noted (CME group: 2 vs. non-CME group: 5; P < 0.702).
      CONCLUSION: CME appears to be a safe procedure when performed by experienced
      hands through proper embryological planes. It also provides a superior specimen,
      with a higher lymph node yield, which consequently affects the lymph node ratio.
      Eventually, CME with CVL should be increasingly adopted and studied more deeply.

PMID- 30208682
TI  - Gland Attenuation, a Novel Morphological Feature of Colorectal Cancer: Evidence
      for an Epithelial-Mesenchymal Transition.
AB  - PURPOSE: Along the invasive margin, colorectal cancer may show distinctive
      morphologic changes characterized by an asymmetrically attenuating tumor gland
      with loss of polarity. The author coined the term 'gland attenuation (GA)' for
      these peculiar changes. The aims of this study were to compare the
      immunoreactivity of the epithelial-mesenchymal transition (EMT) markers E
      cadherin and beta-catenin and thus determine whether EMTs occurs at tumor budding
      (TB) or GA sites and to assess the association of TB and/or GA levels with
      clinicopathological parameters and prognosis. METHODS: Expression patterns of E
      cadherin and beta-catenin in the tumor centers at GA and TB sites were examined
      in 101 patients with well or moderately differentiated CRCs, and the prognostic
      significance of TB and/or GA was statistically evaluated. RESULTS: GA foci, as
      well as TB foci, revealed loss of membranous and cytoplasmic E-cadherin
      expressions and aberrant beta-catenin expression with reduced membranous
      expression and increased localization to the nucleus, suggesting that EMTs occur
      in GA as well as in TB. The high-TB and the TB-dominant groups were significantly
      correlated with advanced invasion depth, presence of lymph node metastasis,
      advanced pathologic staging and presence of lymphovascular invasion. The high-TB
      and the TB-dominant groups showed poor overall survival (OS) and recurrence-free
      survival (RFS), and high TB was an independent prognostic factor in the
      multivariate analyses for OS and RFS. CONCLUSION: This study showed evidence that
      EMTs occurs at GA sites as well as TB foci. TB is a strong and independent
      prognostic factor, and TB-dominance may be an indicator of adverse clinical
      outcome.

PMID- 30208684
TI  - Characteristics and Survival of Korean Patients With Colorectal Cancer Based on
      Data From the Korea Central Cancer Registry Data.
AB  - PURPOSE: The incidence of colorectal cancer (CRC) in Korea has increased
      remarkably during the past few decades. The present study investigated the
      characteristics and survival of patients with CRC in Korea as a function of time,
      tumor distribution, stage, sex, and age. METHODS: We retrieved clinical data on
      326,712 CRC patients diagnosed between 1996 and 2015 from the Korea Central
      Cancer Registry. The incidence and the 5-year relative survival rates were
      compared across time period, tumor distribution, stage, sex, and age group.
      RESULTS: The percentage of patients with colon cancer increased from 49.5% in
      1996-2000 to 66.4% in 2011-2015 while the percentage of patients with rectal
      cancer decreased from 50.5% to 33.6%. The 5-year relative survival rates for all
      CRCs improved from 58.7% in 1996-2000 to 75.0% in 2011-2015. For 1996-2000,
      survival rates were highest for patients with left-sided colon cancers, followed
      by those with right-sided, transverse, rectal, rectosigmoid cancers. For 2011
      2015, the survival rates for patients with left-sided cancers were highest,
      followed by those with rectosigmoid, rectal, transverse, and right-sided colon
      cancers. Patients with local and regional, but not distant, SEER (Surveillance,
      Epidemiology, and End Results) stage tumors experienced significantly increased
      survival rates for 2006-2010 and 2011-2015. The proportion of CRC patients by age
      decreased in the order >=70, 60-69, 50-59, 40-49, <=39 years whereas survival
      rates decreased in the order 50-59, 60-69, 40-49, <=39, >=70 years. CONCLUSION:
      Korean CRC has some distinct characteristics and survival patterns in terms of
      tumor distribution, stage, sex, and age. With time, survival outcomes have
      improved for both local and regional, but not distant, stage tumors.

PMID- 30208683
TI  - Lifestyle Factors and Bowel Preparation for Screening Colonoscopy.
AB  - PURPOSE: The quality of bowel preparation is a major determinant of the quality
      of colonoscopy. This study evaluated lifestyle factors, including usual dietary
      style, associated with bowel preparation. METHODS: This retrospective study
      evaluated 1,079 consecutive subjects who underwent complete colonoscopy from
      December 2012 to April 2014 at National Cancer Center of Korea. Questionnaires on
      bowel preparation were completed by the subjects, with the quality of bowel
      preparation categorized as optimal (excellent or good) or suboptimal (fair, poor
      or inadequate). Lifestyle factors associated with bowel preparation were
      analyzed. RESULTS: The 1,079 subjects included 680 male (63.0%) and 399 female
      patietns (37.0%), with a mean age of 49.6 +/- 8.32 years. Bowel preparation was
      categorized as optimal in 657 subjects (60.9%) and as suboptimal in 422 (39.1%).
      Univariate analyses showed no differences between groups in lifestyle factors,
      such as regular exercise, alcohol intake, smoking, and dietary factor. Body mass
      index (BMI) > 25 kg/m2 was the only factor associated with suboptimal bowel
      preparation on both the univariate (P = 0.007) and the multivariate (odds ratio,
      1.437; 95% confidence interval, 1.104-1.871; P = 0.007) analyses. CONCLUSION:
      Most lifestyle factors, including dietary patterns, exercise, alcohol intake and
      smoking, were not associated with suboptimal bowel preparation in Koreans.
      However, BMI > 25 kg/m2 was independently associated with suboptimal bowel
      preparation. More intense preparation regimens before colonoscopy can be helpful
      in subjects with BMI > 25 kg/m2.

PMID- 30208685
TI  - Effects of dietary humic acid and enzymes on meat quality and fatty acid profiles
      of broiler chickens fed canola-based diets.
AB  - Objective: This study was conducted to assess the effect of potassium humate and
      enzymes (Xylanase + Amylase + Protease) inclusions in diets on carcass
      characteristics, meat quality and fatty acid profiles of broilers fed canola
      based diets. Methods: Two hundred and twenty broilers randomly allotted to 5
      dietary treatments: the control (commercial broiler diet); CM (17.5 % canola meal
      inclusion); CMEnz (17.5% CM inclusion + 0.3 g/kg Axtra XAP); CMPh (17.5% CM
      inclusion + 1.5% Potassium Humate, PH) and CMEnzPh (17.5% CM inclusion + 1.5% PH
      + 0.3 g/kg Axtra XAP) were slaughtered at day 42 for assessment of carcass and
      meat quality parameters. Results: Diet had no effect on carcass traits apart from
      breast muscle weight and breast muscle index. The highest breast muscle weight
      was observed in broilers fed CMEnz (487.6 +/- 17.5 g) followed by those fed the
      control diet (474.37 +/- 17.5 g). Diet also had no significant dietary effect on
      pH, temperature, drip loss and shear force values of the breast muscle. However,
      diet significantly affected meat colour and water-holding capacity (WHC).
      Broilers in the control and CMPh groups (52.94 +/- 0.67 and 52.91+/- 0.67) had
      the highest (P <0.05) values for lightness (L*), whilst those fed CMEnzPh had the
      lowest value (47.94 +/- 0.67). In contrast, CM group had the lowest (P <0.05)
      value for redness (a*) with CMEnzPh group having the highest values. The
      proportion of PUFAs, n-6 and n-3 fatty acids and the PUFA/SFA ratio were
      increased in CM-based diets containing enzymes and humic acid. Conclusion: It
      can, therefore, be concluded that CM can be included in broiler diets in the
      presence of enzymes and humic acid with positive effects on meat quality and
      important fatty acids that are beneficial to the health of consumers.

PMID- 30208686
TI  - Effects of exercise on myokine gene expression in horse skeletal muscles.
AB  - Objective: To examine the regulatory effects of exercise on myokine expression in
      horse skeletal muscle cells, we compared the expression of several myokine genes
      (interleukin 6 (IL-6), interleukin 8 (IL-8), chemokine (C-X-C motif) ligand 2
      (CXCL2), and chemokine (C-C motif) ligand 4 (CCL4)) after a single bout of
      exercise in horses. Furthermore, to establish in vitro systems for the validation
      of exercise effects, we cultured horse skeletal muscle cells and confirmed the
      expression of these genes after treatment with hydrogen peroxide. Methods: The
      mRNA expression of IL-6, IL-8, CXCL2, and CCL4 after exercise in skeletal muscle
      tissue was confirmed using quantitative-reverse transcriptase polymerase chain
      reactions (qRT-PCR). We then extracted horse muscle cells from the skeletal
      muscle tissue of a neonatal Thoroughbredhorses. Myokine expression after hydrogen
      peroxide treatments was confirmed using qRT-PCR in horse skeletal muscle cells.
      Results: IL-6, IL-8, CXCL2, and CCL4 expression in Thoroughbred and Jeju horse
      skeletal muscles significantly increased after exercise. We stably maintained
      horse skeletal muscle cells in culture and confirmed the expression of the
      myogenic marker, myoblast determination protein (MyoD). Moreover, myokine
      expression was validated using hydrogen peroxide (H2O2)-treated horse skeletal
      muscle cells. The patterns of myokine expression in muscle cells were found to be
      similar to those observed in skeletal muscle tissue. Conclusion: We confirmed
      that several myokines involved in inflammation were induced by exercise in horse
      skeletal muscle tissue. In addition, we successfully cultured horse skeletal
      muscle cells and established an in vitro system to validate associated gene
      expression and function. This study will provide a valuable system used to study
      the function of exercise-related genes in the future.

PMID- 30208688
TI  - Effects of short-term fasting on in vivo rumen microbiota and in vitro rumen
      fermentation characteristics.
AB  - Objective: Fasting may lead to changes in the microbiota and activity in the
      rumen. The objective of the present study was to evaluate the effects of fasting
      on rumen microbiota and the impact of fasting on in vitro rumen fermentation
      using molecular culture-independent methods. Methods: Three ruminally cannulated
      Holstein steers were fed rice straw and concentrates. The ruminal fluids were
      obtained from the same steers 2 h after the morning feeding (control) and 24 h
      after fasting (fasting). The ruminal fluid was filtrated through four layers of
      muslin, collected for a culture-independent microbial analysis, and used to
      determine the in vitro rumen fermentation characteristics. Total DNA was
      extracted from both control and fasting ruminal fluids. The rumen microbiota was
      assessed using denaturing gradient gel electrophoresis (DGGE) and quantitavtive
      PCR. Microbial activity was evaluated in control and fasting steers at various
      intervals using in vitro batch culture with rice straw and concentrate at a ratio
      of 60:40. Results: Fasting for 24 h slightly affected the microbiota structure in
      the rumen as determined by DGGE. Additionally, several microorganisms, including
      Anaerovibrio lipolytica, Eubacterium ruminantium, Prevotella albensis, Prevotella
      ruminicola, and Ruminobacter amylophilus, decreased in number after fasting. In
      addition, using the ruminal fluid as the inoculum after 24 h of fasting, the
      fermentation characteristics differed from those obtained using non-fasted
      ruminal fluid. Compared with the control, the fasting showed lower total gas
      production, ammonia, and microbial protein production (p < 0.05). No significant
      differences, however, was observed in pH and dry matter digestibility.
      Conclusion: When in vitro techniques are used to evaluate feed, the use of the
      ruminal fluid from fasted animals should be used with caution.

PMID- 30208687
TI  - Hair follicle development and related gene and protein expression of skins in Rex
      rabbits during the first 8 weeks of life.
AB  - Objective: We aimed to observe hair follicle (HF) development in the dorsal skin
      and elucidate the expression patterns of genes and proteins related to skin and
      HF development in Rex rabbits from birth to 8 weeks of age. Methods: Whole-skin
      samples were obtained from the backs of Rex rabbits at 0, 2, 4, 6 and 8 weeks of
      age, the morphological development of primary and secondary HFs was observed, and
      the gene transcript levels of insulin-like growth factor-I (IGF-I), epidermal
      growth factor (EGF), bone morphogenetic protein 2 (BMP2), transforming growth
      factor beta-1, 2 and 3 (TGFbeta-1, TGFbeta-2 and TGFbeta-3) were examined using
      quantitative real-time PCR. Additionally, Wnt10b and beta-Catenin gene and
      protein expression were examined by quantitative real-time PCR and western blot,
      respectively. Results: The results showed significant changes in the
      differentiation of primary and secondary HFs in Rex rabbits during their first 8
      weeks of life. The IGF-I, EGF, TGFbeta-2 and TGFbeta-3 transcript levels in the
      rabbits were significantly lower at 2 weeks of age than at birth and gradually
      increased thereafter, while the BMP2 and TGFbeta-1 transcript levels at 2 weeks
      of age were significantly higher than those at birth and gradually decreased
      thereafter. beta-Catenin gene expression was also significantly affected by age,
      while the Wnt10b transcript level was not. However, the Wnt10b and beta-catenin
      protein expression levels were the lowest at 2 and 4 weeks of age. Conclusion:
      Our data showed that a series of changes in HFs in dorsal skin occurred during
      the first 8 weeks. Many genes, such as IGF-I, EGF, BMP2, TGFbeta-1, TGFbeta-2,
      TGFbeta-3 and beta-Catenin, participated in this process, and the related
      proteins Wnt10b and beta-Catenin in skin were also affected by age.

PMID- 30208689
TI  - Method development to reduce the fiber content of wheat bran and rice bran
      through anaerobic fermentation with rumen liquor for use in poultry feed.
AB  - Objective: Wheat bran (WB) and rice bran (RB) are the agricultural by-products
      used as poultry feed in many developing countries. However, their use for poultry
      feed is limited due to high fiber and the presence of anti-nutritional substances
      (e.g. beta-glucans). The objective of this study was to develop a method to
      improve the quality of those brans by reducing the fiber content. Methods: A two
      step fermentation method was developed where the second fermentation of first
      fermented dry bran was carried out. Fermentation was performed at a controlled
      environment for 3h and 6h (n=6). The composition of brans, buffer solution and
      rumen liquor was maintained in a ratio of 1:2:3, respectively. Brans were
      analyzed for dry matter (DM), crude fiber (CF), acid detergent fiber (ADF),
      neutral detergent fiber (NDF) and acid detergent lignin (ADL) content. Celluloses
      and hemicelluloses were calculated from the difference of ADF-ADL and NDF-ADF,
      respectively. Samples were compared by two-factor ANOVA followed by Tukey's
      multiple comparison tests (p < 0.05). Results: CF % ADF % and cellulose tended to
      decrease and NDF % and hemicellulose content was reduced significantly (p <
      0.05). After the 1st fermentation step, NDF decreased 10.7+/-0.55 % after 3h
      versus 17.0+/-0.78 % after 6h in case of WB. Whereas, these values were 2.3 +/-
      0.30 % (3h) and 7.5+/-0.69 % (6h) in case of RB. However, after the 2nd
      fermentation step, the decrease in the NDF content amounted to 9.1+/-0.72 % (3h),
      17.4+/-1.13 % (6h) and 9.3+/-0.46 % (3h), 10.0+/-0.68 % (6h) in WB and RB,
      respectively. Cellulose and hemicellulose content was reduced up to 15.6+/-0.85 %
      (WB), 15.8+/-2.20 % (RB) and 36.6+/-2.42 % (WB), 15.9+/-3.53 % (RB), respectively
      after 2nd fermentation of 6h. Conclusion: Two-step fermentation process improved
      the quality of the brans for their use in poultry feed.

PMID- 30208690
TI  - Potential to mitigate ammonia emission from slurry by increasing dietary
      fermentable fiber through inclusion of tropical byproducts in practical diets for
      growing pigs.
AB  - Objective: Research was conducted to test the effect of including fiber-rich
      feedstuffs in practical pig diets on nutrient digestibility, nitrogen balance and
      ammonia emissions from slurry. Methods: Three Vietnamese fibre sources were
      screened, namely cassava leaf meal (CL), cassava root residue (CR) and tofu by
      product (TF). Accordingly, a control diet (Con) with 10% of dietary non-starch
      polysaccharides (NSP) and three test diets including one of the three fiber-rich
      feedstuffs to reach 15% of NSP were formulated. All formulated diets had the same
      level of crude protein, in vitro ileal protein digestible and metabolisable
      energy, whereas the in vitro hindgut VFA production of the test diets was 12 to
      20% higher than the control diet. Forty growing barrows with initial body weight
      at 28.6 +/- 1.93 kg (M+/-SD) were allocated to the four treatments. When pigs
      reached about 50 kg of body weight, four pigs from each treatment were used for a
      nitrogen balance trial and ammonia emission assessment, the remaining six pigs
      continued the second period of the feeding trial. Results: The TF treatment
      increased faecal VFA by 33% as compared with the control treatment (P = 0.07),
      suggesting stimulation of the hindgut fermentation. However, urinary N was not
      significantly reduced or shifted to faecal N, nor was slurry pH decreased.
      Accordingly, ammonia emissions were not mitigated. CR and CL treatments failed to
      enhance in vivo hindgut fermentation, as assessed by faecal VFA and purine bases.
      On the contrary, the reduction of CP digestibility in the CL treatment enhanced
      (P = 0.051) ammonia emissions from slurry. Conclusion: Modest dietary inclusion
      of tropical byproducts to increase fermentable fiber might stimulate faecal VFA
      excretion but this does not guarantee a reduction in ammonia emissions from
      slurry, while its interaction with protein digestibility even might increase the
      risk of enhanced ammonia emissions.

PMID- 30208691
TI  - The alternative approach of low temperature-long time cooking on bovine
      semitendinosus meat quality.
AB  - Objective: This study aimed to elucidate whether innovative sous vide treatment
      have a significant influence on the beef semitendinosus muscle as compared to
      common sous vide treatment and traditional cooking. Methods: The innovative sous
      vide treatments were cooked at 45 and 65  degrees C for 6 h (SV45-65), common
      sous vide treatment at 45 and 65  degrees C for 3 h (SV45 and SV65) and
      traditional cooking at 75  degrees C for 30 min (CON75). Water loss and cooking
      loss, as well as the physical properties (color and shear force) and chemical
      properties (protein and collagen solubility) of the treated meat, were
      investigated. Results: The results obtained indicated that the innovative sous
      vide with double thermal treatment (SV45-65) and cooked with air presence (CON75)
      resulted to lower a* and higher b* values, respectively. The water loss and
      cooking loss increased when temperature increased from 45 to 65  degrees C, and
      lower water loss was recorded in SV45 and CON75. These samples presented higher
      water content and revealed strong correlation to protein solubility. Warner
      Bratzler shear force analysis (SF) showed the marked interaction between cooking
      temperature and time. Sample cooked at a high temperature (CON75) and a long
      period (SV45-65) showed a significantly lower value of SF than sample SV65 (p <
      0.05). Interestingly, there was no difference in SF values between SV45-65 and
      CON75. Conclusion: The innovative sous vide treatment with double thermal effect
      appears an attractive cooking method as compared to common sous vide and
      traditional cooking method, as it has a potential for improving tenderness values
      of cooked beef semitendinosus muscle.

PMID- 30208692
TI  - Hepatic miRNAome Reveals Potential miRNA-mRNA Pairs Associated with Lipid
      Metabolism in Pigs.
AB  - Objective: As one of the most important metabolic organs, the liver plays vital
      roles in modulating the lipid metabolism. This study was to compare miRNA
      expression profiles of the Large White liver between two different developmental
      periods and to identify candidate miRNAs for lipid metabolism. Methods: Eight
      liver samples were collected from White Large of 70-day fetus (P70) and of 70-day
      piglets (D70) (with 4 biologocal repeats at each development period) to construct
      sRNA libraries. Then the eight prepared sRNA libraries were sequenced using
      Illumina next-generation sequencing techonogy on HiSeq 2500 platform. Results: As
      a result, we obtained 346 known and 187 novel miRNAs. Compared with the D70, 55
      down- and 61 up-regulated miRNAs were shown to be significantly differentially
      expressed (DE). GO and KEGG enrichment analysis indicated that these DE miRNAs
      were mainly involved in growth, development and diverse metabolic processes. They
      were predicted to regulate lipid metabolism through Adipocytokine signaling
      pathway, MAPK, AMPK, cAMP, PI3K-AKT, and Notch signaling pathway. miR-122, miR
      26a and miR-30a-5p, which play important roles in lipid metabolism, were the most
      abundantly expressed (miR-122 only in P70). Integration analysis (details of
      mRNAs sequencing data were shown in another unpublished paper) revealed that many
      target genes of the DE miRNAs (miR-181b, miR-145-5p, miR-199a-5p and miR-98)
      might be critical regulators in lipid metabolic process, including ACSL4, ABCA4
      and SCD. Thus, these miRNAs were considered to be the promising candidates for
      lipid metabolism. Conclusion: Our study provides the main differences in the
      Large White at miRNA level between two different developmental stages. It
      supplies a valuable database for the further function and mechanism elucidation
      of miRNAs in porcine liver development and lipid metabolism.

PMID- 30208693
TI  - Effects of a tunnel ventilation system within the tie-stall barn environment upon
      the productivity of dairy cattle during the winter season.
AB  - Objective: The objective of this study was to examine the effect of using a
      tunnel ventilation system within the dairy barn environment upon the productivity
      of dairy cows during the winter season. Methods: The study was performed at the
      University Farm, Faculty of Agriculture, Utsunomiya University. Twenty-one
      Holstein dairy cows (5 heifers and 16 multiparous) were enclosed in a stall barn.
      Unventilated (UV) and tunnel-ventilated (TV) was operated by turns every one
      week, and a number of key parameters were measured in the barn, including tunnel
      ventilation output, temperature, relative humidity, gas concentrations (oxygen
      [O2], carbon dioxide [CO2] and ammonia [NH3]). Also ten cows were used to measure
      the skin and rectal temperature, respiratory rate, blood gas concentrations, and
      bacterial count from nipple attachments. The amount of fodder left uneaten, and
      general components and somatic cell count (SCC) of the milk were measured.
      Results: As for our dairy barn environment, air temperature dropped significantly
      with the passage of time with TV. Humidity was significantly higher with TV at
      0600 h compared to UV, while CO2 and NH3 concentrations with UV were
      significantly higher than with TV at 0000 h and 0600 h. Skin temperature was
      significantly lower with TV compared to UV at 0000 h and 0600 h. Respiratory rate
      was also significantly lower at 0600 h with TV than with UV. Bacterial count for
      the nipple attachments was significantly lower with TV than with UV at 0600 h.
      The amount of leftover fodder was significantly less with TV in comparison with
      UV. Conclusion: Our results suggest that a TV system in the winter barn results
      in environmental improvements, such as reductions in unfavorable gas
      concentrations and bacterial growth. Consequently, it is expected that barns
      utilizing a TV system will be beneficial for both animal health and production.

PMID- 30208694
TI  - Enteric methane emissions, energy partitioning, and energetic efficiency of zebu
      beef cattle fed total mixed ration silage.
AB  - Objective: The main objective of this study was to evaluate the effect of
      different feeding levels of a total mixed ration silage-based diet on feed
      intake, total tract digestion, enteric methane emissions, and energy partitioning
      in two beef cattle genotypes. Methods: Six mature bulls (three Thai natives, and
      three Thai natives - Charolais crossbreeds) were assigned in a replicated 3 * 3
      Latin square design, with cattle breed genotype in separate squares, three
      periods of 21 days, and three energy feeding above maintenance levels (1.1, 1.5,
      and 2.0 MEm, where MEm is metabolizable energy requirement for maintenance).
      Bulls were placed in a metabolic cage equipped with a ventilated head box
      respiration system to evaluate digestibility, record respiration gases, and
      determine energy balance. Results: Increasing the feeding level had no
      significant effect on digestibility but drastically reduced the enteric methane
      emission rate (p<0.05). Increasing the feeding level also significantly increased
      the energy retention and utilization efficiency (p<0.01). The Thai native cattle
      had greater enteric methane emission rate, digestibility, and energy utilization
      efficiency than the Charolais crossbred cattle (p<0.05). The daily metabolizable
      energy requirement for maintenance in Thai native cattle (388 kJ/kg BW0.75, where
      BW0.75 is metabolic body weight) was 15% less than that in Charolais crossbred
      cattle (444 kJ/kg BW0.75). Conclusion: Our results suggested that the greater
      feeding level in zebu beef cattle fed above maintenance levels resulted in
      improved energy retention and utilization efficiency because of the reduction in
      enteric methane energy loss. The results also indicated higher efficiency of
      metabolisable energy utilization for growth and a lower energy requirement for
      maintenance in B. indicus than in B. taurus.

PMID- 30208695
TI  - Changes in expression of the autophagy-related genes MAP1LC3B and ATG7 in
      skeletal muscle of fattening Japanese Black cattle: a pilot study.
AB  - Objective: Autophagy is a bulk degradation system for intracellular proteins
      which contributes to skeletal muscle homeostasis, according to previous studies
      in humans and rodents. However, there is a lack of information on the
      physiological role of autophagy in the skeletal muscle of meat animals. This
      study was planned as a pilot study to investigate changes in expression of two
      major autophagy-related genes, microtubule-associated protein 1 light chain 3beta
      (MAP1LC3B) and autophagy related 7 (ATG7) in fattening beef cattle, and to
      compare them with skeletal muscle growth. Methods: Six castrated Japanese Black
      cattle (initial body weight: 503 +/- 20 kg) were enrolled in this study, and
      fattened for 7 months. Three skeletal muscles, M. longissimus, M. gluteus medius
      and M. semimembranosus, were collected by needle biopsy three times during the
      observation period, and mRNA levels of MAP1LC3B and ATG7 were determined by qRT
      PCR. The expression levels of genes associated with the ubiquitin-proteasome
      system, another proteolytic mechanism, were also analyzed for comparison with
      autophagy-related genes. In addition, ultrasonic scanning was repeatedly
      performed to measure M. longissimus area as an index of muscle growth. Results:
      Our results showed that both MAP1LC3B and ATG7 expression increased over the
      observation period in all three skeletal muscles. Interestingly, the increase in
      expression of these two genes in M. longissimus was highly correlated with
      ultrasonic M. longissimus area and body weight. On the other hand, the expression
      of genes associated with the ubiquitin-proteasome system was unchanged during the
      same period. Conclusion: These findings suggest that autophagy plays an important
      role in the growth of skeletal muscle of fattening beef cattle, and imply that
      autophagic activity affects meat productivity.

PMID- 30208696
TI  - Risk factors limiting first service conception rate in dairy cows, and their
      economic impact.
AB  - Objective: We determined the risk factors limiting first service conception (FSC)
      rate in dairy cows and their economic impact. Methods: Data were collected from
      790 lactations regarding cow parity, peri- and postpartum disorders, body
      condition score (BCS), reproductive performance, and expenses associated with
      reproductive management (treatment, culling, and others). Initially, we
      identified the risk factors limiting FSC rate in dairy cows. Various biological
      and environmental factors, such as herd, cow parity, BCS at 1 month postpartum
      and first artificial insemination (AI), resumption of cyclicity within 1 month of
      calving, year, AI season, insemination at detected estrus or timed AI, peri- and
      postpartum disorders, and calving to first AI interval, were evaluated. Next, we
      evaluated the economic impact of the success or failure of FSC by comparing the
      expense associated with reproductive management until conception between cows
      that did or did not conceive at their first service. Results: Cows with BCS < 3.0
      had a lower probability of conceiving at first insemination (odds ratio [OR] =
      0.64, p < 0.05) than cows with BCS >= 3.0. Cows inseminated during summer were
      less likely to conceive (OR = 0.44, p < 0.001) than cows inseminated during
      spring. Cows with peri- or postpartum disorders were less likely to conceive (OR
      = 0.55, p < 0.001) than cows without disorders. Survival curves generated using
      MedCalc showed an 81 day extension in the mean interval between calving and
      conception in cows that failed to conceive over those that did conceive at first
      insemination. Cows failing conceive required additional expenditure on
      reproductive treatment ($55.40) and other management ($567.00) than cows that
      conceived at first insemination. Conclusion: Lower BCS, hot weather at first
      insemination, and peri- and postpartum disorders are risk factors limiting FSC,
      which result in an economic loss of $622.40 per dairy cow.

PMID- 30208697
TI  - Soybean meal substitution by dehulled lupine (Lupinus angustifolius) with enzymes
      in broiler diets.
AB  - Objective: Evaluate the effects of 1) dehulling of lupine seed on chemical
      composition and apparent metabolizable energy (AME) and 2) soybean meal
      substitution by dehulled lupine seed in broiler diets with enzymes on productive
      performance, size of digestive organs and welfare-related variables. Methods:
      Experiment 1. Chemical composition and AME were determined in whole and dehulled
      lupine seed. Experiment 2. Two hundred eighty-eight one-day-old male Ross 308
      broilers were used. The experimental diets were maize-soybean meal (MS), MS with
      enzymes (MSE) and maize-dehulled lupine seed with enzymes (MLE). Diets were
      assigned to the experimental units under a completely randomized design (eight
      replicates per diet). The BW gain, feed intake, feed conversion, digestive organ
      weights, gait score, latency to lie down and valgus/varus angulation were
      evaluated. Results: The dehulling process increased protein (25.0 to 31.1%), AME
      (5.9 to 8.8 MJ/kg) and amino acid contents. The BW gain of broilers fed the MLE
      diet was similar (P > 0.05) to that of those fed the MS diet, but lower than that
      of those fed the MSE diet. Feed intake of broilers fed the MLE diet was higher (P
      < 0.05) than that of those fed the MS diet and similar (P > 0.05) to those fed
      the MSE diet. Feed conversion of broilers fed the MLE diet was 8.0 and 8.7%
      higher (P < 0.05) than that of those fed the MS and MSE diets, respectively.
      Broilers fed the MLE diet had the highest (P < 0.05) relative proventriculus and
      gizzard weights, but had poor welfare-related variables. Conclusion: It is
      possible to substitute soybean meal by dehulled lupine seed with enzymes in
      broiler diets, obtaining similar BW gains in broilers fed the MLE and MS diets;
      however, a higher feed intake is required. Additionally, the MLE diet reduced
      welfare-related variables.

PMID- 30208698
TI  - Comparative study of thermal gelation properties and molecular forces of
      actomyosin extracted from normal and pale, soft and exudative (PSE)-like chicken
      breast meat.
AB  - Objective: The objectives of this study were to investigate the thermal gelation
      properties and molecular forces of actomyosin extracted from two classes of
      chicken breast meat qualities (normal and PSE-like) during heating process to
      further improve the understanding of the variations of functional properties
      between normal and PSE-like chicken breast meat. Methods: Actomyosin were
      extracted from normal and PSE-like chicken breast meat and the gel strength,
      water-holding capacity (WHC), protein loss, particle size and distribution,
      dynamic rheology and protein thermal stability were determined, then turbidity,
      active sulfhydryl group contents, hydrophobicity and molecular forces during
      thermal-induced gelling formation were comparatively studied. Results: SDS-PAGE
      showed that protein profiles of actomyosin extracted from normal and PSE-like
      meat were not significantly different (P>0.05). Compared with normal actomyosin,
      PSE-like actomyosin had lower gel strength, WHC, particle size, less protein
      content involved in thermal gelation forming (P<0.05), and reduced onset
      temperature (To), thermal transition temperature (Td), storage modulus (G') and
      loss modulus (G"). The turbidity, reactive sulfhydryl group of PSE-like
      actomyosin were higher when heated from 40 degrees C to 60 degrees C. Further
      heating to 80 degrees C had lower transition from reactive sulfhydryl group into
      a disulfide bond and surface hydrophobicity. Molecular forces showed that
      hydrophobic interaction was the main force for heat-induced gel formation while
      both ionic and hydrogen bonds were different significantly between normal and PSE
      like actomyosin (P<0.05). Conclusion: These changes in chemical groups and inter
      molecular bonds affected protein-protein interaction and protein-water
      interaction and contributed to the inferior thermal gelation properties of PSE
      like meat.

PMID- 30208699
TI  - Carcass characteristics and meat quality of purebred Pakchong 5 and crossbred
      pigs sired by Pakchong 5 or Duroc boar.
AB  - Objective: This study investigated carcass characteristics and meat quality of
      purebred Pakchong 5, crossbred pigs sired by Pakchong 5, and crossbred pigs sired
      by Duroc. Methods: Forty-eight pigs (average body weight, BW of 22.25 kg) were
      composed of three groups as purebred Pakchong 5 (PP), Large White x Landrace pigs
      sired by Pakchong 5 (LWLRP), and Large White x Landrace pigs sired by Duroc
      (LWLRD). Each group consisted of eight gilts and eight barrows. At 109-day
      raising period, pigs were slaughtered and carcass characteristics were evaluated.
      Longissimus thoracis (LT) muscles from left side of carcasses were evaluated for
      meat quality and chemical composition. Data were analyzed using GLM procedure,
      where group, sex, and their interaction are included in the model. Results: PP
      had greater carcass, total lean, and ham percentages than crossbred pigs (p <
      0.05). LWLRP had thicker backfat and more carcass fat percentage than LWLRD (p <
      0.05). There were no differences (p > 0.05) on cutting percentages from tender
      loin, loin, boston butt, and picnic shoulder among groups. PP and LWLRP had
      larger loin eye area (LEA) than LWLRD (p < 0.05). Gilts had more loin percentage
      and lower L* value than barrows (p < 0.05). No meat color parameters (L*, a* and
      b*) were affected by groups (p > 0.05). PP and LWLRP had larger muscle fiber
      diameters than LWLRD (p < 0.05). However, water holding capacity, Warner-Bratzler
      shear force values, and chemical composition of LT were not affected by group or
      sex (p > 0.05). Conclusion: Pakchong 5 purebred has good carcass and lean
      percentages. Compared to Duroc crossbred pigs, Pakchong 5 crossbreds have similar
      carcass and lean percentages, larger LEA, and slightly more carcass fat, with
      comparable meat quality and chemical composition. Pakchong 5 boars are more
      affordable for very small- to medium-scale pig producers.

PMID- 30208702
TI  - An Innovative Portable Biosensor System for the Rapid Detection of Freshwater
      Cyanobacterial Algal Bloom Toxins.
AB  - Harmful algal blooms in freshwater systems are increasingly common and present
      threats to drinking water systems, recreational waters, and ecosystems. A highly
      innovative simple to use, portable biosensor system (MBio) for the rapid and
      simultaneous detection of multiple cyanobacterial toxins in freshwater is
      demonstrated. The system utilizes a novel planar waveguide optical sensor that
      delivers quantitative fluorescent competitive immunoassay results in a disposable
      cartridge. Data are presented for the world's first duplex microcystin
      (MC)/cylindrospermopsin (CYN) assay cartridge using a combination of fluorophore
      conjugated monoclonal antibodies as detector molecules. The on-cartridge
      detection limits of 20% inhibitory concentration (IC20) was 0.4 MUg/L for MC and
      0.7 MUg/L for CYN. MC assay coverage of eight important MC congeners was
      demonstrated. Validation using 45 natural lake water samples from Colorado and
      Lake Erie showed quantitative correlation with commercially available laboratory
      based enzyme linked immunosorbent assays. A novel cell lysis module was
      demonstrated using cyanobacteria cultures. Results show equivalent or better
      performance than the gold-standard but more tedious 3* freeze-thaw method, with
      >90% cell lysis for laboratory cultures. The MBio system holds promise as a
      versatile tool for multiplexed field-based cyanotoxin detection, with future
      analyte expansion including saxitoxin, anatoxin-a, and marine biotoxins.

PMID- 30208701
TI  - Trends in Micropollutant Biotransformation along a Solids Retention Time
      Gradient.
AB  - For many polar organic micropollutants, biotransformation by activated sludge
      microorganisms is a major removal process during wastewater treatment. However,
      our current understanding of how wastewater treatment operations influence
      microbial communities and their micropollutant biotransformation potential is
      limited, leaving major parts of observed variability in biotransformation rates
      across treatment facilities unexplained. Here, we present biotransformation rate
      constants for 42 micropollutants belonging to different chemical classes along a
      gradient of solids retention time (SRT). The geometric mean of biomass-normalized
      first-order rate constants shows a clear increase between 3 and 15 d SRT by 160%
      and 87%, respectively, in two experiments. However, individual micropollutants
      show a variety of trends. Rate constants of oxidative biotransformation reactions
      mostly increased with SRT. Yet, nitrifying activity could be excluded as primary
      driver. For substances undergoing other than oxidative reactions, i.e., mostly
      substitution-type reactions, more diverse dependencies on SRT were observed. Most
      remarkably, characteristic trends were observed for groups of substances
      undergoing similar types of initial transformation reaction, suggesting that
      shared enzymes or enzyme systems that are conjointly regulated catalyze
      biotransformation reactions within such groups. These findings open up
      opportunities for correlating rate constants with measures of enzyme abundance
      such as genes or gene products, which in turn should help to identify enzymes
      associated with the respective biotransformation reactions.

PMID- 30208700
TI  - Eriodictyol Attenuates LPS-Induced Neuroinflammation, Amyloidogenesis, and
      Cognitive Impairments via the Inhibition of NF-kappaB in Male C57BL/6J Mice and
      BV2 Microglial Cells.
AB  - Eriodictyol, a natural flavonoid mainly distributed in citrus fruits and peanut,
      has been well-documented with possession of excellent anti-inflammatory,
      antioxidant, and anticancer bioactivities. This work focus on the protective
      effects of eriodictyol on LPS-induced neuroinflammation, amyloidogenesis,
      cognitive impairment, and the potential mechanisms involved. Behavioral tests and
      histological examinations showed that eriodictyol significantly prevented the
      memory and neuronal damage triggered by LPS. Consistently, eriodictyol (100
      mg/kg) reduced the formation of Abeta1-42 by 28.37 +/- 16.71 pg/mL compared to
      the LPS group. In addition, high dose eriodictyol (100 mg/kg) also equilibrated
      the cholinergic system via suppressing AChE activity (0.1996 +/- 0.0831 U/mgprot)
      and elevating ChAT activity (41.81 +/- 24.72 U/g) as well as ACh level (5.093 +/-
      3.531 MUg/mgprot) compared to the LPS group. Western blot results indicated that
      compared to the LPS group, eriodictyol suppressed LPS-induced glial
      overactivation (84.29% +/- 27.21%) and regulated inflammatory mediators and
      cytokines by inhibiting the NF-kappaB and MAPK pathways. These results indicated
      that eriodictyol alleviated amyloidogenesis and memory impairment triggered by
      LPS via inhibiting TLR4, MAPKs, and PI3K/Akt, and activating Sirt1 pathways and
      thus blocking downstream translocation of NF-kappaB, which offers a potential
      nutritional preventive strategy for neuroinflammation diseases such as
      Alzheimer's disease (AD).

PMID- 30208703
TI  - An Aminoimidazole Radical Intermediate in the Anaerobic Biosynthesis of the 5,6
      Dimethylbenzimidazole Ligand to Vitamin B12.
AB  - Organisms that perform the de novo biosynthesis of cobalamin (vitamin B12) do so
      via unique pathways depending on the presence of oxygen in the environment. The
      anaerobic biosynthesis pathway of 5,6-dimethylbenzimidazole, the so-called "lower
      ligand" to the cobalt center, has been recently identified. This process begins
      with the conversion of 5-aminoimidazole ribotide (AIR) to 5-hydroxybenzimidazole
      (HBI) by the radical S-adenosyl-l-methionine (SAM) enzyme BzaF, also known as HBI
      synthase. In this work we report the characterization of a radical intermediate
      in the reaction of BzaF using electron paramagnetic resonance spectroscopy. Using
      various isotopologues of AIR, we extracted hyperfine parameters for a number of
      nuclei, allowing us to propose plausible chemical compositions and structures for
      this intermediate. Specifically, we find that an aminoimidazole radical is formed
      in close proximity to a fragment of the ribose ring. These findings induce the
      revision of past proposed mechanisms and illustrate the ability of radical SAM
      enzymes to tightly control the radical chemistry that they engender.

PMID- 30208704
TI  - Breakthroughs in the Health Effects of Plant Food Bioactives: A Perspective on
      Microbiomics, Nutri(epi)genomics, and Metabolomics.
AB  - Plant bioactive compounds consumed as part of our diet are able to influence
      human health. They include secondary metabolites like (poly)phenols, carotenoids,
      glucosinolates, alkaloids, and terpenes. Although much knowledge has been gained,
      there is still need for studies unravelling the effects of plant bioactives on
      cardiometabolic health at the individual level, using cutting-edge high
      resolution and data-rich holistic approaches. The aim of this Perspective is to
      review the prospects of microbiomics, nutrigenomics and nutriepigenomics, and
      metabolomics to assess the response to plant bioactive consumption while
      considering interindividual variability. Insights for future research in the
      field toward personalized nutrition are discussed.

PMID- 30208705
TI  - Comparative Transcriptome Analysis Revealed the Tissue-Specific Accumulations of
      Taxanes among Three Experimental Lines of Taxus yunnanensis.
AB  - Taxus yunnanensis (Yew) is known for natural anticancer metabolite paclitaxel
      (Taxol) and its biosynthesis pathway in yew species still needs to be completely
      elucidated. In the current study, productions of paclitaxel and 10-DAB III from
      three different tissues (needle, branch, and root) of T. yunnanensis wild type
      (WT) and two new cultivars Zhongda-1 (Zd1) and Zhongda-2 (Zd2) were determined,
      and significant tissue differences in contents of the taxanes were observed among
      the three experimental lines. The much higher 10-DAB III and lower paclitaxel
      contents in needle of Zd2 when compared with that of Zd1 indicated the low
      conversion from 10-DAB III to paclitaxel in the needle of Zd2. In order to
      uncover the mechanisms of the tissue-specific biosynthesis of the taxanes,
      transcriptome analysis of cultivar Zd2 was conducted, and the previously reported
      transcriptome data of Zd1 and WT were used to perform a comparison. The
      enhancement of TDAT and T10betaH side biosynthetic pathway in roots of Zd2 in
      early taxane synthesis might lead to the biosynthesis of other toxoids, while the
      preference of T13alphaH route in the needle and branch of Zd2 was mainly
      responsible for the tissue-specific reinforced biosynthesis of 10-DAB III and
      paclitaxel in Zd2. Different from Zd1, the tissue-specific pattern of paclitaxel
      biosynthesis genes in Zd2 was similar to WT. However, the lower transcript
      abundance of final steps genes (TBT, DBAT, BAPT, and DBTNBT) of the paclitaxel
      biosynthesis pathway in Zd2 than in Zd1 might further promote 10-DAB III
      accumulation in Zd2.

PMID- 30208706
TI  - Modulation of Enhanced Antioxidant Activity by Hydrogen Sulfide Antagonization of
      Ethylene in Tomato Fruit Ripening.
AB  - Ethylene (C2H4) and hydrogen sulfide (H2S) play important physiological roles in
      regulating fruit ripening and senescence. The mechanism of H2S in ethylene
      induced tomato fruit ripening and senescence is still unknown. Here, we show that
      exogenous H2S reduced the production of superoxide anion (.O2-), malondialdehyde
      (MDA), and H2O2 in tomato fruit. Further, additional H2S was found to induce the
      activities of guaiacol peroxidase, catalase, ascorbate peroxidase, and superoxide
      dismutase compared with C2H4 treatment alone, whereas the activities of
      lipoxygenase, polyphenol oxidase, and phenylalanine ammonia lyase were adversely
      affected. Moreover, the expression of the antioxidant-encoding genes SlAPX2,
      SlCAT1, SlPOD12, and SlCuZnSOD was generally up-regulated with C2H4-H2S
      cotreatment, compared with their expression after ethylene treatment. Thus, the
      present results suggest that exogenous H2S acts as a fruit-ripening regulator by
      antagonizing the effect of ethylene, thereby providing a potential application
      for H2S in the postharvest storage of fruit.

PMID- 30208707
TI  - Identification of Peptide Biomarkers for Discrimination of Shrimp Species through
      SWATH-MS-Based Proteomics and Chemometrics.
AB  - Incorrect labeling and adulteration of shrimp occurs due to interspecies
      similarities and carapace removal during processing. This study attempted to
      identify three related commercial shrimp species of the order Decapoda:
      Marsupenaeus japonicus, Fenneropenaeus chinensis, and Litopenaeus vannamei. All
      measurable trypsin-digested peptides in the individual shrimp were detected using
      ultrahigh-performance liquid chromatography quadrupole time-of-flight (UPLC-Q
      TOF) mass spectrometry with sequential window acquisition of all theoretical
      fragment ion spectra (SWATH) data-independent acquisition. Further analysis of
      peptide biomarkers was carried out with an orthogonal partial least-squares
      discriminant analysis (OPLS-DA) model. BLAST was used for species-specific
      analysis. Subsequently, multiple reaction monitoring (MRM) methods were developed
      for sensitivity and selectivity screening of the selected peptides, and 27 were
      identified as biomarkers allowing rapid and accurate discrimination of shrimp
      species without high-resolution mass spectrometry or statistical model building.
      These strategies could be applied in authentication of other products containing
      highly homologous proteomes.

PMID- 30208708
TI  - A Multiscale Simulation Approach to Modeling Drug-Protein Binding Kinetics.
AB  - Drug-target binding kinetics has recently emerged as a sometimes critical
      determinant of in vivo efficacy and toxicity. Its rational optimization to
      improve potency or reduce side effects of drugs is, however, extremely difficult.
      Molecular simulations can play a crucial role in identifying features and
      properties of small ligands and their protein targets affecting the binding
      kinetics, but significant challenges include the long time scales involved in
      (un)binding events and the limited accuracy of empirical atomistic force fields
      (lacking, e.g., changes in electronic polarization). In an effort to overcome
      these hurdles, we propose a method that combines state-of-the-art enhanced
      sampling simulations and quantum mechanics/molecular mechanics (QM/MM)
      calculations at the BLYP/VDZ level to compute association free energy profiles
      and characterize the binding kinetics in terms of structure and dynamics of the
      transition state ensemble. We test our combined approach on the binding of the
      anticancer drug Imatinib to Src kinase, a well-characterized target for cancer
      therapy with a complex binding mechanism involving significant conformational
      changes. The results indicate significant changes in polarization along the
      binding pathways, which affect the predicted binding kinetics. This is likely to
      be of widespread importance in binding of ligands to protein targets.

PMID- 30208709
TI  - Vibrational Predissociation Spectroscopy of Cold Protonated Tryptophan with
      Different Messenger Tags.
AB  - Vibrational spectra of protonated tryptophan were recorded by predissociation of
      H2 messenger tags using cryogenic ion traps. We explore the issue of messenger
      induced spectral changes by solvating TrpH+(H2) n with n = 1-5 to obtain single
      photon vibrational spectra of TrpH+ and of its partly deuterated isotopomer in
      the spectral region of 800-4400 cm-1. Depending on the number of messenger
      molecules, the spectra of several conformational isomers associated with multiple
      H2 binding locations along with two natural conformations of TrpH+ were found
      using the two photon MS3IR2 conformational hole burning method. Most probable
      messenger positions were established by comparison with predictions from DFT
      calculations on various candidate structures. Mechanical anharmonicity effects
      associated with the charged amino group were modeled by Born-Oppenheimer ab
      initio molecular dynamics. The spectra of TrpH+(H2O) m=1,2, recorded by infrared
      multiphoton dissociation (IRMPD), reveal broad features in the NH stretching
      region of the NH3+ group, indicating strong hydrogen bonding in acceptor-donor
      configuration with the benzene ring for the first water molecule, while the
      second water appears to attach to a less strongly perturbing site, yielding
      unique transitions associated with the free OH stretching fundamentals. We
      discuss the structural deformations induced by the water molecules and compare
      our results to recent experiments on similar hydrated cationic systems.

PMID- 30208710
TI  - Electronic Resonant Stimulated Raman Scattering Micro-Spectroscopy.
AB  - Recently we have reported electronic pre-resonance stimulated Raman scattering
      (epr-SRS) microscopy as a powerful technique for super-multiplex imaging ( Wei,
      L. ; Nature 2017 , 544 , 465 - 470 ). However, under rigorous electronic
      resonance, background signal, which mainly originates from pump-probe process,
      overwhelms the desired vibrational signature of the chromophores. Here we
      demonstrate electronic resonant stimulated Raman scattering (er-SRS)
      microspectroscopy and imaging through suppression of electronic background and
      subsequent retrieval of vibrational peaks. We observed a change of the
      vibrational band shapes from normal Lorentzian, through dispersive shapes, to
      inverted Lorentzian as the electronic resonance was approached, in agreement with
      theoretical prediction. In addition, resonant Raman cross sections have been
      determined after power-dependence study as well as Raman excitation profile
      calculation. As large as 10-23 cm2 of resonance Raman cross section is estimated
      in er-SRS, which is about 100 times higher than previously reported in epr-SRS.
      These results of er-SRS microspectroscopy pave the way for the single-molecule
      Raman detection and ultrasensitive biological imaging.

PMID- 30208711
TI  - Performance Comparison of Three Chemical Vapor Deposited Aminosilanes in Peptide
      Synthesis: Effects of Silane on Peptide Stability and Purity.
AB  - Silicon oxide substrates underwent gas-phase functionalization with various
      aminosilanes, and the resulting surfaces were evaluated for their suitability as
      a solid support for solid phase peptide synthesis (SPPS). APTES (3
      aminopropyltriethoxysilane), APDEMS (3-aminopropyldiethoxymethylsilane), and
      APDIPES (3-aminopropyldiisopropylethoxysilane) were individually applied to
      thermal oxide-terminated silicon substrates via gas-phase deposition. Coated
      surfaces were characterized by spectroscopic ellipsometry (SE), contact angle
      goniometry, X-ray photoelectron spectroscopy (XPS), atomic force microscopy
      (AFM), and spectrophotometry. Model oligopeptides with 16 residues were
      synthesized on the amino surfaces, and the chemical stabilities of the resulting
      surfaces were evaluated against a stringent side chain deprotection (SCD) step,
      which contained trifluoroacetic acid (TFA) and trifluoromethanesulfonic acid
      (TFMSA). Functionalized surface thickness loss during SCD was most acute for
      APDIPES and the observed relative stability order was APTES > APDEMS > APDIPES.
      Amino surfaces were evaluated for compatibility with stepwise peptide synthesis
      where complete deprotection and coupling cycles are paramount. Model trimer
      syntheses indicated that routine capping of unreacted amines with acetic
      anhydride significantly increased purity as measured by MALDI-MS. An inverse
      correlation between the amine loading density and peptide purity was observed. In
      general, peptide purity was highest for the lowest amine density APDIPES surface.

PMID- 30208712
TI  - Covalent Cross-Linking of Diketopyrrolopyrrole-Based Organogels with
      Polydiacetylenes.
AB  - A new strategy toward functional materials with novel properties and well-defined
      structures has been developed through the topochemical polymerization of
      diacetylene-containing diketopyrrolopyrrole (DPP) derivatives. In order to enable
      the efficient photopolymerization and cross-linking of the materials, a rational
      design of DPP-based derivatives has been performed to incorporate amide moieties,
      thus enabling the formation of intermolecular hydrogen bonds and the formation of
      an organogel. The new materials showed good gelation properties in aromatic
      solvents, resulting in the formation of a dense fibrous network in the gel state.
      Upon UV irradiation, the supramolecular self-assemblies obtained were shown to be
      efficiently cross-linked through the conversion of diacetylene into
      polydiacetylene. A detailed investigation of new resulting materials was
      performed by a combination of morphological characterization tools, including X
      ray diffraction, Raman spectroscopy, and atomic force microscopy. Our results
      demonstrate that the topochemical polymerization of diacetylene-containing DPP
      based compounds is a promising strategy toward new electroactive and well-defined
      materials, without the use of catalysts or additives, thus creating new
      opportunities for the preparation and processing of pi-conjugated materials.

PMID- 30208714
TI  - Guest Editorial.

PMID- 30208713
TI  - He's here and he's gone; he's here and he's gone ... The experiences of new
      mothers in rural Newfoundland and Labrador, Canada, whose partners work away from
      home.
AB  - : Introduction Employment-related mobility (ERM) is a complex phenomenon that
      impacts family life. New mothers who have partners working away from home for
      intermittent and extended periods of time are particularly affected. As these
      families transition to parenting roles they are further challenged with the
      expectation that the mother manages sole responsibility for family and home life
      while her partner works away. METHODS: A hermeneutic phenomenology approach was
      used to explore the experiences of new mothers on the island portion of rural
      Newfoundland and Labrador, Canada, whose partners participated in ERM.
      Participants were recruited through community health nurses and family resource
      center staff. Semi-structured interviews were conducted, audio-recorded,
      transcribed and analyzed following Ricoeur's approach. RESULTS: The essence of
      the experience of these 19 women was apparent in their stories of adjustment to
      periods of transition when their partner was working away from home. Five themes
      were generated from interpretation of the experiences of the participants: 'he's
      here and he's gone again', 'one-woman show', 'putting myself on the back burner',
      'the routine goes out the window' and 'making it work'. CONCLUSIONS: While many
      women felt overwhelmed with the responsibilities of balancing family life, and
      often experienced loneliness, others described a smoother adaptation to an ERM
      lifestyle. The experiences of the mothers warrant consideration to inform health
      care providers, policymakers and community leaders to be more responsive to the
      emerging needs of families in these situations.

PMID- 30208720
TI  - Infrared Spectral Emissivity Property of Pure Titanium in the 473-1035 K
      Temperature Range.
AB  - The normal infrared (IR) spectral emissivity of pure titanium TA1 is
      experimentally investigated using a self-designed emissivity measurement
      apparatus. The apparatus and the measurement method are described in detail.
      Seven samples are treated with abrasive paper to obtain the roughness needed. The
      emissivity of one sample is obtained between 473 and 1035 K with wavelength range
      of 3-27 um in an argon environment. The other six samples are oxidized at a high
      temperature (873 K) for various times. The surface roughness and composition of
      the samples are analyzed using roughness tester and X-ray diffraction before and
      after the emissivity measurement. The results show that the spectral emissivity
      of titanium sample increases with the increase of temperature and decreases with
      the increase of wavelength from 3 to 27 um. For the oxidized samples, the
      spectral emissivity increases with increasing oxidization time, and after being
      heated for 12 h, the emissivity values increase slightly. The influence of the
      oxide film thickness on the spectral emissivity is discussed based on
      interference theory, and the thickness of oxide film with different oxidation
      time is accurately measured using scanning electron microscope.

PMID- 30208721
TI  - A Simple Route to Synthesize Cu@Ag Core-Shell Bimetallic Nanoparticles and Their
      Surface-Enhanced Raman Scattering Properties.
AB  - Water-dispersed Cu@Ag core-shell nanoparticles (NPs) with 15 nm-diameter Cu core
      and 5 nm-thick Ag shell can be synthesized by a facile one-step chemical
      reduction at room temperature without any protective atmosphere. To obtain a
      homogeneous Ag coating on Cu, the influence of [Cu/Ag] molar ratio was
      investigated. Transmission electron microscopy (TEM) and X-ray diffraction (XRD)
      confirmed that Ag formed a dense coating on the surface of Cu, and that phase
      pure spherical Cu@Ag core-shell bimetallic NPs were prepared when the [Cu/Ag]
      molar ratio was between 1/0.5 and 1/0.75. The time dependence of ultraviolet
      visible (UV-Vis) spectra and XRD patterns of six-month stored Cu@Ag NPs showed
      that the as-prepared Cu@Ag NPs have a long-term antioxidant activity. Also, the
      surface-enhanced Raman scattering (SERS) signals had a high stability and
      reproducibility for the substrates. Hence, the as-prepared Cu@Ag nanostructures
      can be used as an efficient substrate for SERS signals.

PMID- 30208726
TI  - Primary cardiac natural killer/T-cell lymphoma, a very rare form of lymphoma.
AB  - Extranodal natural killer/T-cell lymphoma is a rare non-Hodgkin lymphoma that is
      divided into nasal, non-nasal, and aggressive/leukemia subtypes, according to
      anatomic origin and clinical manifestations, with each subtype carrying a
      different prognosis. We present a case of primary cardiac natural killer/T-cell
      lymphoma with extension to other organs in a 38-year-old man, to highlight the
      role of imaging in categorizing nasal versus non-nasal types. This distinction
      has relevant implications for patient care because the non-nasal type has a much
      lower survival rate.

PMID- 30208725
TI  - "It's a disease of families": Neurologists' insights on how to improve
      communication and quality of life for families of Parkinson's disease patients.
AB  - Objectives Parkinson's disease presents an evolving challenge for patients and
      families due to an unpredictable disease trajectory and symptoms that complicate
      social interactions. In this study, we explore neurologists' perspectives on the
      challenges Parkinson's disease presents for families and the strategies they use
      to improve communication and quality of life. Methods We conducted hour-long semi
      structured interviews with 16 neurologists at 4 care delivery institutions in the
      San Francisco Bay Area, focusing on techniques neurologists use to support
      families through the Parkinson's disease journey. Results Neurologists identified
      strategies for addressing caregiver-patient disagreements around symptom accuracy
      and negotiating driving safety. Family education is needed to contextualize
      patient symptoms and to identify psychosocial support resources. Unmet caregiver
      needs remain, particularly in the form of psychosocial support, respite care and
      support for unequal gender dynamics in the Parkinson's disease caregiving
      experience. Discussion Family members of Parkinson's disease patients face unique
      caregiving and interpersonal challenges due to the nature of the disease.
      Targeted education and structural support are needed to alleviate current burdens
      and allow for improved patient- and family-centered care.

PMID- 30208727
TI  - Improved Analysis of Manganese in Steel Samples Using Collinear Long-Short Double
      Pulse Laser-Induced Breakdown Spectroscopy (LIBS).
AB  - A long-short double pulse laser-induced breakdown spectroscopy (long-short DP
      LIBS) method was employed to improve the analytical performance of LIBS for the
      measurement of manganese in steel samples. The long pulse with a duration of 60
      MUs was generated using a neodymium-doped yttrium aluminum garnet (Nd:YAG) laser
      which was operated at free-running (FR) mode. To investigate the detection
      ability without sample preparation, the steel washers were tested using single
      pulse LIBS (SP-LIBS) and long-short DP-LIBS, respectively. The measurement
      results show that long-short DP-LIBS was able to record clear spectra from the
      steel washers with a surface layer. Through the observation on the laser craters
      with a scanning electron microscope (SEM), the results suggest that the
      improvement in detection ability can be attributed to the pre-irradiation effect
      of long-pulse laser beam. Next, the analytical performance for quantitative
      measurement of manganese was evaluated employing ten standard steel samples. The
      results show that the linearity fit (R2) of the calibration curve is 0.988 for
      long-short DP-LIBS, whereas, R2 is only 0.810 for SP-LIBS under the same
      measurement conditions. The repeated measurement results show that the average
      relative standard deviation (RSD) of the tested samples is 29.3% for SP-LIBS and
      is 10.5% for long-short DP-LIBS. The prediction results also show that the
      average relative error of prediction (REP) is 94.9% for SP-LIBS and is 4.9% for
      long-short DP-LIBS.

PMID- 30208729
TI  - In vivo genotoxicity assessment of sunset yellow and sodium benzoate in female
      rats.
AB  - The use of additives in different food products is growing up. It has attracted
      the attention towards the relation between the mutagenic potential of human
      diseases and food additives. Sunset yellow (SY) and sodium benzoate (NaB) are
      used as colorant and food additives worldwide. In the present study, genotoxic
      effects of different combinations of SY and NaB were assessed in vivo in female
      rats. Different combinations of SY and NaB were dissolved in water and
      administered daily to six animals groups for 12 weeks. Group 1 (control) received
      water, Group 2 received 5 mg/kg body weight (bw) SY plus 10 mg/kg bw NaB, group 3
      received 5 mg/kg SY plus 100 mg/kg NaB, group 4 received 50 mg SY plus 100 mg/kg
      NaB, group 5 received 50 mg/kg SY plus 10 mg/kg NaB, group 6 received 200 mg/kg
      SY plus 750 mg/kg NaB, and group 7 received 20 mg/kg SY plus 75 mg/kg NaB.
      Genotoxicity investigations (Chromosomal aberration of bone marrow cells, Comet
      assay and DNA profile of liver cells) were carried out at the end of the
      experiment. Administration of 200 mg/kg SY plus 750 mg/kg NaB (group 6) induced
      the highest abnormalities percentage (1.5%) and showed structural abnormalities
      including end-to-end association, fragmentation, chromatid break, ring
      chromosome, and centric fusion break of chromosomes. Different combinations of SY
      and NaB induced an increase in the frequency of tailed nuclei (DNA damage) in
      liver cells. A concentration-dependent distinct DNA smear pattern was observed in
      the DNA isolated from liver cells of animals administered SY and NaB. In
      addition, administration of SY plus NaB resulted in an abnormal distribution of
      serum proteins. The results showed that the SY plus NaB could have genotoxic
      potential. With the increase applications of food additives, this study reported
      important data about screening the potential impacts.

PMID- 30208728
TI  - Functional modulation of caecal fermentation and microbiota in rat by feeding
      bean husk as a dietary fibre supplement.
AB  - A feeding study using rats was conducted to evaluate the utility of lablab bean
      husk and soya bean husk as sources of potential prebiotic fibre. Twenty 5-week
      old Sprague Dawley rats were divided into 4 groups and fed one of the following
      diets for 3 weeks: purified diet (AIN93 G) containing 5% cellulose (CEL), or the
      same diet in which cellulose was replaced by corn starch (STA), lablab bean husk
      (LBH), or soya bean husk (SBH). Rats were sacrificed at 8 weeks of age and caecal
      digesta were collected. Feed intake, body weight, anatomical parameters, and
      caecal ammonia level did not differ significantly among diets. Rats on LBH and
      SBH showed higher concentrations of caecal short-chain fatty acid and lactate
      than those on CEL. Rats on CEL, SBH, and LBH exhibited lower caecal indole and
      skatole levels. LBH yielded increased caecal abundance of Akkermansia muciniphila
      and Oscillibacter relatives, as demonstrated by either qPCR, MiSeq, or clone
      library analysis. SBH favoured the growth of lactobacilli as assessed by both
      qPCR and MiSeq, and favoured the growth of bifidobacteria as assessed by MiSeq.
      In comparison with STA, LBH and SBH yielded lower caecal abundance of bacteria
      related to Dorea massiliensis, as demonstrated by qPCR, MiSeq, and clone library
      analysis. Both types of bean husk were found to contain oligosaccharides that
      might selectively stimulate the growth of beneficial bacteria. Based on these
      results, the two species of bean husk tested are considered potentially
      functional for promoting the gut health of monogastric animals.

PMID- 30208730
TI  - Language, disfigurement, stigma and clothing.

PMID- 30208731
TI  - Announcing the Primer in Genetics and Genomics Series.

PMID- 30208732
TI  - A Viewpoint on the Leaky Gut Syndrome to Treat Allergic Asthma: A Novel Opinion.
AB  - Asthma is a common respiratory disease characterized by airway inflammation,
      airway hyperreactivity, and reversible airflow obstruction. Despite current
      treatments, the prevalence of asthma has increased markedly over decades.
      According to the theories proposed to explain the pathophysiology of autoimmune
      diseases in integrative medicine, leaky gut syndrome is a phenomenon of increased
      intestinal permeability due to the disruption of tight junctions and is thought
      to be related to many chronic diseases, such as food intolerance, inflammatory
      bowel disease, rheumatoid arthritis, asthma, and other autoimmune disease. One of
      the classical approaches used by integrative physicians to treat leaky gut
      syndrome is to repair intestinal permeability to prevent allergic cascade. Due to
      several mechanisms that have been mentioned in the protective effects of plant
      gums and plantain family seeds on the intestinal epithelium, we can propose an
      effective management for leaky gut syndrome to treat asthma.

PMID- 30208733
TI  - Cancer and Cancer-Related Fatigue and the Interrelationships With Depression,
      Stress, and Inflammation.
AB  - Cancer-related fatigue (CRF) is a common symptom experienced in cancer patients.
      Depression, anxiety, and stress are associated with cancer. Depression and
      anxiety are also associated with CRF. At the cellular level, much is known about
      the impact of stress on the body generally, and its potential role in cancer.
      Stress, anxiety, and depression have been found to depress the immune system.
      Depression and stress have also been found to create inflammatory changes in the
      body and there is emerging evidence that inflammation is involved in cancer
      pathogenesis and in CRF. This article examines the relationships between stress,
      anxiety, depression, and cancer; relationships between anxiety and depression and
      CRF; and what happens at the cellular level, including impact on the immune
      system and emerging evidence of the role of inflammation in CRF. It also reports
      on research in relation to some Chinese herbal medicines that may be used to
      treat CRF.

PMID- 30208734
TI  - Dietary Recommendations in Fracture Healing in Traditional Persian Medicine: A
      Historical Review of Literature.
AB  - BACKGROUND: Fracture repair is a complex process. An inappropriate diet is a
      contributing risk factor for fracture nonunion. The aim of this study was to
      extract dietary recommendations for fracture healing according to traditional
      Persian medicine (TPM) literature. METHOD: The contents relevant to diets in
      fracture healing were selected from main textbooks in TPM like Al Qanon fi Al-teb
      ( The Canon). Other reference textbooks in traditional medicine were also used
      for a comprehensive study in this respect. Finally content analysis was used for
      summarizing and describing the results. FINDINGS: Food stuffs are classified in
      TPM according to their nutritive value, their assimilability, and the quality of
      achieved chyme. Some light meals like chicken soup are recommended for the early
      days of fracture and high-nutrient and dense foods such as goat's or sheep's head
      and nuts are advised in following days for fracture healing acceleration and
      callus formation. Several recommendations are also provided for pacing the
      healing process. CONCLUSION: A comparison of Avicenna and other Persian sage's
      recommended regimens with the recent evidence revealed the potential positive
      effects of their regimen for bone healing acceleration. It can shed light on a
      part of history of orthopedics and add to current knowledge about bone fracture
      and its management.

PMID- 30208736
TI  - A Mindfulness-Based Intervention Pilot Feasibility Study for Elementary School
      Students With Severe Learning Difficulties: Effects on Internalized and
      Externalized Symptoms From an Emotional Regulation Perspective.
AB  - OBJECTIVE: Students with severe learning disabilities often show signs of
      anxiety, depression, and problem behaviors such as inattention and conduct
      problems. Mindfulness-based interventions (MBIs) in school settings constitute a
      promising option to alleviate these co-occurring symptoms. This pilot study aimed
      to evaluate the impact of an MBI on symptoms and behaviors of elementary school
      students with severe learning disabilities. METHOD: A one-group pretest-posttest
      design was used. The sample comprised 14 students aged 9 to 12 years with special
      education needs. Both student-report and teacher-report of the Behavior
      Assessment System for Children, Second Edition were used. RESULTS: Repeated
      measures analyses of variance revealed a significant impact of the MBI on
      symptoms and behaviors such as anxiety, depression, inattention, aggression, and
      conduct problems. Effect sizes for all variables were considered large (partial
      eta2 = .31-.61). CONCLUSION: These preliminary results indicate that MBIs can
      reduce the frequency of symptoms and problem behaviors often found in children
      with learning disabilities in elementary schools. Further multiple baseline
      experimental trials with a long-term follow-up are warranted to establish more
      robustly the effect of MBIs for children with learning disabilities.

PMID- 30208735
TI  - A Qualitative Study of Mindfulness Among Veterans With Posttraumatic Stress
      Disorder: Practices Differentially Affect Symptoms, Aspects of Well-Being, and
      Potential Mechanisms of Action.
AB  - This qualitative study explored and compared the subjective experiences of 102
      veterans with posttraumatic stress disorder (PTSD) who were randomly assigned to
      1 of 4 arms: ( a) body scan, ( b) mindful breathing, ( c) slow breathing, or ( d)
      sitting quietly. Qualitative data were obtained via semistructured interviews
      following the intervention and analyzed using conventional content analysis. The
      percentage of participants within each intervention who endorsed a specific theme
      was calculated. Two-proportion z tests were then calculated to determine if the
      differences among themes endorsed in specific groups were statistically
      significant. Six core themes emerged from analysis of participant responses
      across the 4 groups: ( a) enhanced present moment awareness, ( b) increased
      nonreactivity, ( c) increased nonjudgmental acceptance, ( d) decreased
      physiological arousal and stress reactivity, ( e) increased active coping skills,
      and ( f) greater relaxation. More participants in the mindfulness intervention
      groups reported improvement in PTSD symptoms when compared to participants in non
      mindfulness groups. Different types of intervention targeted different symptoms
      and aspects of well-being. Furthermore, type of intervention may have also
      differentially targeted potential mechanisms of action. This article highlights
      the importance of employing both quantitative and qualitative research methods
      when investigating the dynamic process of mindfulness and may inform how
      practices can be tailored to the needs of the veteran with PTSD.

PMID- 30208737
TI  - The Role of Phlebotomy ( Fasd) and Wet Cupping ( Hijamat) to Manage Dizziness and
      Vertigo From the Viewpoint of Persian Medicine.
AB  - Dizziness and vertigo are the most common complaints of patients that has a high
      economic burden on the health system. In modern medicine, treatment for dizziness
      and vertigo consists of chemical pharmacological therapy. Although these drugs
      are useful in controlling the disease, their side effects and inefficiency in
      full control of the disease require the use of complementary medicine in this
      field. Persian medicine consists of valuable experiences of Persian medicine
      scholars based on the theory of humors and temperaments. In Persian medicine, 2
      types of disease are presented: dizziness ( sadar) and vertigo ( dovar). Persian
      medicine physicians expressed a different mechanism of action than modern
      medicine for these diseases. They believed that accumulation of abnormal humors,
      reeh (normal bloating) or causative pathologic substances, is the basic cause of
      sadar and dovar and that the most important treatment is cleansing the body,
      particularly the head from accumulated substances by bloodletting methods.

PMID- 30208738
TI  - Design and synthesis of novel organometallic complexes using boronated
      phenylalanine derivatives as potential anticancer agents.
AB  - Drug design and discovery studies are important because of the prevalence of
      diseases without available medical cures. New anticancer agents are particularly
      urgent because of the high mortality rate associated with cancer. A series of
      mononuclear gold (III) and platinum (II) complexes based on boronated
      phenylalanine (BPA) were designed and synthesized using 4,4'-dimethyl-2,2'
      dipyridyl (L1) or 1,10-phenanthroline-5,6-dion (L2) ligands to obtain promising
      anticancer drug candidates. Proton nuclear magnetic resonance, infrared, mass
      spectrometry, and elemental analyses were utilized for chemical
      characterizations. Cell viability, cancer cell colony formation, endothelial tube
      formation, and cytoskeleton staining assays were performed using A549 lung
      adenocarcinoma and human umbilical vein endothelial cells (HUVECs) to investigate
      preliminary pharmacological activities. L1-based platinum (II) complex (BPA-L1
      Pt) was the most promising complex, and has similar activity with the approved
      chemotherapy drug cis-platinum. Half maximal inhibitory concentration values for
      BPA-L1-Pt were 9.15 uM on A549s and 16.61 uM on HUVECs; the values for cis
      platinum were 5.24 uM on A549s and 23.14 uM on HUVECs. Consequently, further
      synthesis studies should be performed to boost the cancer cell selectivity
      feature of BPA by varying metal and ligand types.

PMID- 30208739
TI  - Roles of miR-200 family members in lung cancer: more than tumor suppressors.
AB  - miRNAs are a class of single-stranded noncoding RNAs, which have no coding
      potential, but modulate many molecular mechanisms including cancer pathogenesis.
      miRNAs participate in cell proliferation, differentiation, apoptosis, as well as
      carcinogenesis or cancer progression, and their involvement in lung cancer has
      been recently shown. They are suggested to have bidirectional functions on
      important cancer-related genes so as to enhance or attenuate tumor genesis.
      Epithelial-mesenchymal transition (EMT) is a fundamental process which
      contributes to integrity of organogenesis and tissue differentiation as well as
      tissue repair, organ fibrosis and the progression of carcinoma, and several
      miRNAs were suggested to form the network regulating EMT in lung cancer, among
      which, miR-200 family members (miR-200a, miR-200b, miR-200c, miR-429 and miR-141)
      play crucial roles in the suppression of EMT.

PMID- 30208740
TI  - Long intergenic noncoding RNA 299 methylation in peripheral blood is a biomarker
      for triple-negative breast cancer.
AB  - AIM: To identify DNA methylation biomarkers in peripheral blood samples from
      triple-negative breast cancer (TNBC) patients. MATERIALS & METHODS: We conducted
      an epigenome-wide association study (EWAS): the most promising markers were
      identified in 233 TNBC case-control pairs (discovery set) and subsequently
      validated in an independent validation set (57 TNBC patients and 124 controls).
      RESULTS: cg06588802 (LINC00299/ID2) showed a higher methylation in TNBC patients
      compared with controls (discovery set: 3% increase, p-value = 0.0009; validation
      set: 2% increase, p-value = 0.01). Consistent results at four neighboring
      methylation probes and the strong negative correlation (rho = -0.93) with
      LINC00299 expression add plausibility to this result. CONCLUSION:
      Hypermethylation of LINC00299 in peripheral blood may constitute a useful
      circulating biomarker for TNBC.

PMID- 30208741
TI  - Special Issue Editor's Overview Essay.

PMID- 30208742
TI  - Involvement of metallothionein, homocysteine and B-vitamins in the attenuation of
      arsenic-induced uterine disorders in response to the oral application of hydro
      ethanolic extract of Moringa oleifera seed: a preliminary study.
AB  - The painful invasive chelation therapy makes it challenging to continue the
      prolonged treatment against arsenic toxicity. Hence, the significance of the
      present preliminary investigation was to explore a noninvasive treatment strategy
      against sodium arsenite (As3+) by the use of a hydroethanolic extract of Moringa
      oleifera (MO) seed. Arsenic treatment (10 mg/kg body-weight) in animals showed
      significant level of oxidative stress as evidenced by increased serum levels of
      malondialdehyde (MDA), conjugated dienes (CD) and reduced level of non-protein
      thiol (NPSH). A significant diminution in the activities of enzymatic
      antioxidants was noted in As3+-treated rats. As3+ treatment showed a lengthy
      phase of metestrous in animals followed by significantly diminished ovarian
      steroidogenesis, increased ovarian follicular degeneration and distortion of
      uterine tissue histomorphology. In addition, there was a significant depletion of
      Vitamin-B9 (folate) and B12 following As3+ ingestion. The levels of circulating
      TNF-alpha, homocysteine (Hcy), uterine-IL-6, and liver metallothionein (MT-1)
      were significantly elevated in arsenic treated rats. MO at a dose of 100 mg/kg
      body-weight could successfully mitigate the uterine ROS generation by maintaining
      the uterine antioxidant status in As3+- treated rats. This seed extract prevented
      the deterioration of As3+-mediated ovarian-steroidogenesis and ovarian and
      uterine histoarchitecture significantly. B9 and B12 levels were also improved
      following the ingestion of the MO extract in arsenicated animals. Elevation of
      Hcy, TNF-alpha and IL-6 was also prevented by this MO seed extract in As3+
      treated rats. A further increase of MT-1 level was achieved after MO ingestion in
      As3+-treated rats. Here, the alleviation of arsenic toxicity might involve via
      the regulation of the components of S-adenosine methionine (SAM) pool and MT-1.

PMID- 30208743
TI  - Hair straightening products and the risk of occupational formaldehyde exposure in
      hairstylists.
AB  - Hair straitening products are widely used by hairstylists. Many keratin-based
      hair smoothing products contain formaldehyde. This study aimed to investigate
      occupational formaldehyde exposure among hairstylists dealing with hair
      straightening products and the relation between genotoxicity biomarkers and the
      short-term formaldehyde exposure concentrations and the working years. The study
      was carried out in Cairo, Egypt on 60 hairstylists use hair straightening
      products divided into two groups according to the working years. All hairstylists
      were subjected to micronucleus (MN) frequencies in both epithelial buccal cells
      (EBC) and peripheral blood lymphocytes (PBL). Fifteen-minute (min) formaldehyde
      exposure concentrations were measured at workplace during hair straightening
      procedure. Fifteen-minute formaldehyde concentrations in both groups exceeded the
      National Institute for Occupational Safety and Health and the American Conference
      of Governmental Industrial Hygienist thresholds levels. The MN frequencies in EBC
      and PBL showed a significant increase in group II in comparison to control and
      group I, which in turn showed a significant increase in MN frequency in PBL and a
      nonsignificant increase in the MN frequency in EBC when compared to control. A
      positive correlation was found between genotoxicity biomarkers and working years.
      Occupational exposures to hair straightening products in the studied hairstylist
      were found to expose them to formaldehyde concentrations that exceeded the
      standard limits. All selected genotoxicity biomarkers showed a significant
      increase in exposed workers and were positively correlated to the duration of
      exposure.

PMID- 30208744
TI  - Assessment of complex genomic alterations induced by AZT, 3TC, and the
      combination AZT +3TC.
AB  - Highly active antiretroviral therapy (HAART) regimens are based on the use of
      nucleoside reverse transcriptase inhibitors (NRTIs), which are the main drugs
      used by patients infected with the human immunodeficiency virus (HIV). The use of
      NRTIs combinations has afforded clear clinical benefits to patients undergoing
      HAART. However, the combination of two NRTIs may increase the risk of genomic
      instability in comparison with the drugs administered individually. We analyzed
      the ability of zidovudine (AZT) and lamivudine (3TC), and the combination AZT
      +3TC to induce complex genomic alterations using the cytokinesis-block
      micronucleus (CBMN) assay in Chinese hamster ovary (CHO)-K1 cells. The 24-h cell
      treatment with individual NRTIs showed that AZT increased micronucleus
      frequencies and nucleoplasmic bridges (NPBs). No significant differences were
      observed for any parameters investigated after exposure of CHO-K1 cells to 3TC.
      The combination AZT +3TC significantly increased micronucleus frequencies.
      Analysis of interaction between these drugs suggested that antagonism occurs in
      all AZT +3TC concentrations. These results highlight the importance to
      investigate the genotoxic profile of NRTIs to develop safer intervention
      strategies in antiretroviral treatment protocols.

PMID- 30208746
TI  - Comparison of ultrasound-guided high-intensity focused ultrasound ablation and
      surgery for abdominal wall endometriosis.
AB  - BACKGROUND: Surgery constitutes the standard approach for abdominal wall
      endometriosis (AWE), but is invasive. High-intensity focused ultrasound (HIFU)
      ablation is effective and safe for the treatment of AWE, but no study has
      compared HIFU and surgery. OBJECTIVE: To report our experience about the benefits
      and adverse events of surgery compared to HIFU for the treatment of AWE. METHODS:
      This was a retrospective study of 54 consecutive Chinese women with AWE after
      cesarean section treated at the First Affiliated Hospital of Chongqing Medical
      University (China) between January 2012 and December 2014. The patients underwent
      surgery (n = 29) or HIFU (n = 25). The technical success rate, adverse events,
      and recurrence were assessed. RESULTS: The technical success rate was 100% in
      both groups. The complete remission rate was 92.0% (23/25) in the HIFU group, and
      100% (29/29) in the surgery group. Numeric rating scale (NRS) scores after HIFU
      were significantly improved from 6.9 to 0.3.During the median follow-up period of
      32 months (range, 19-46 months), the durations of pain relief were 29.7 +/- 12.6
      months and 25.0 +/- 13.5 months in the surgery and HIFU groups, respectively (p =
      .337). Three patients (10.7%) experienced pain recurrence in the surgery group,
      and two (8.0%) in the HIFU group. Major adverse events occurred in four (13.8%)
      and one (4.0%) patients in the surgery and HIFU groups, respectively (p > .05).
      CONCLUSIONS: HIFU appears to be beneficial for the treatment of AWE, and may
      reduce adverse events. Compared with surgery, HIFU does not induce blood loss or
      tissue defects.

PMID- 30208747
TI  - Targetability of osteoid osteomas and bone metastases by MR-guided high intensity
      focused ultrasound (MRgHIFU).
AB  - PURPOSE: To retrospectively evaluate the suitability of MRgHIFU for osteoid
      osteomas (OOs) and bone metastases in patients who underwent minimally-invasive
      percutaneous thermal ablation. MATERIALS AND METHODS: One hundred and sixty-seven
      lesions (115 metastases and 52 OOs) treated percutaneously between October 2014
      and June 2017 were retrospectively analyzed. Tumors were located in the spine or
      sacrum (54), pelvis (43), limbs (50), ribs (17) and sternum (3). Tumor volume,
      matrix, anatomical environment and need for protection of surrounding structures
      or consolidation were assessed. Cases were classified into three categories: (a)
      lesions suitable for MRgHIFU therapy alone; (b) lesions suitable for MRgHIFU if
      protection of surrounding structures and/or bone consolidation is performed; (c)
      lesions not suitable for MRgHIFU. RESULTS: Twenty-six (50%) of OOs were
      classified as suitable for MRgHIFU alone and 17 (32.7%) as suitable for MRgHIFU
      with hydro-dissection. Matrix of treatable OOs was sclerotic (19), lytic (15) or
      mixed (9), with mean volume 0.56 cm3. Forty-one (35.7%) of metastases were
      classified as suitable for MRgHIFU alone and 43 (37.4%) as suitable with hydro
      dissection and/or consolidation. Matrix of metastases was sclerotic (13), lytic
      (37) or mixed (34), with mean volume 71.9 cm3. Mean depth of targetable lesions
      was 50.9 +/- 28.4 mm. 97.7% of pelvic lesions and 94% of peripheral bone lesions
      were targetable by HIFU. 66.6% of spinal or sacral lesions were considered
      untreatable. CONCLUSION: MRgHIFU cannot be systematically performed non
      invasively on bone tumors. Combination with minimally-invasive thermo-protective
      techniques may increase the number of eligible cases.

PMID- 30208748
TI  - Positive correlation between cognitive impairment and renal microangiopathy in
      patients with type 2 diabetic nephropathy: a multicenter retrospective study.
AB  - Objective This study was performed to explore the correlation between cognitive
      impairment and renal microangiopathy in patients with type 2 diabetic nephropathy
      (T2DN) by detecting changes in cognitive function and cerebral metabolism in
      these patients with different stages of T2DN. Methods Prospectively maintained
      databases were reviewed from 2006 to 2017. Blood biochemical indexes and the
      urinary albumin excretion rate (UAER) were measured in all participants.
      Cognitive function was assessed by the Mini-Mental State Examination (MMSE) and
      Montreal Cognitive Assessment Scale (MoCA). Cognitive impairment was the primary
      endpoint. Renal microangiopathy was the secondary endpoint. Pearson correlation
      analysis was used to assess correlations. Results Two hundred sixteen patients
      with type 2 diabetes mellitus (T2DM) were divided into three groups according to
      their UAER: T2DM without nephropathy (n=72), early T2DM with nephropathy (n=74),
      and the clinical stage of early T2DM with nephropathy (n=70). Healthy
      participants were selected as the normal control group (n=70). Pearson
      correlation analysis demonstrated that the total MMSE and MoCA score was
      negatively correlated with the UAER (r=-0.327) and positively correlated with the
      estimated glomerular filtration rate (r=0.428) in patients with T2DN. Conclusions
      The present study showed a positive correlation between cognitive impairment and
      renal microangiopathy in patients with T2DN.

PMID- 30208745
TI  - Synthesis and biological evaluation of dithiocarbamate esters of parthenolide as
      potential anti-acute myelogenous leukaemia agents.
AB  - A series of dithiocarbamate esters of parthenolide (PTL) was designed,
      synthesised, and evaluated for their anti- acute myelogenous leukaemia (AML)
      activities. The most promising compound 7l showed greatly improved potency
      against AML progenitor cell line KG1a with IC50 value of 0.7 MUM, and the
      efficacy was 8.7-folds comparing to that of PTL (IC50 = 6.1 MUM). Compound 7l
      induced apoptosis of total primary human AML cells and leukaemia stem cell (LSCs)
      of primary AML cells while sparing normal cells. Furthermore, 7l suppressed the
      colony formation of primary human leukaemia cells. Moreover, compound 12, the
      salt form of 7l, prolonged the lifespan of mice in two patient-derived xenograft
      models and had no observable toxicity. The preliminary molecular mechanism study
      revealed that 7l-mediated apoptosis is associated with mitogen-activated protein
      kinase signal pathway. On the basis of these investigations, we propose that 12
      might be a promising drug candidate for ultimate discovery of anti-LSCs drug.

PMID- 30208750
TI  - Pepper and cinnamon improve cold induced cognitive impairment via increasing non
      shivering thermogenesis; a study.
AB  - Despite an understanding that a major effect of cold exposure is a fall in core
      body temperature which is responsible for the observed decrements in the
      performance, it is surprising that thermogenic supplements are seldom evaluated
      to verify if they can aid in improving the performance during cold exposure.
      Following evidence from our previous study indicating the ability of pepper and
      cinnamon to improve cold endurance, we investigated further here if the improved
      endurance had advantages in real time where they could positively affect
      cognitive performance (assessed by Novel object test) when exposed to cold in
      albino wistar rats. In order to delineate if the observed improvement if any, was
      due to their cognitive enhancing ability or thermogenic potential, distinctive
      room temperature (RT) and cold temperature (CT) groups were used. Cold exposure
      impaired cognitive performance which improved following treatment with both the
      spices. We noted an increased rate of cold adaptive thermogenesis in CT treated
      group as evidenced by an elevated norepinephrine, free fatty acid levels in
      blood, increased expression of UCP1 in brown adipose tissue, the net effect being
      a decreased fall in the core body temperature. Absence of any notable effect in
      these parameters in the RT treated group ascertained that at least in the current
      experimental set up the observed improvement in performance in CT treated group
      is due to the thermogenic potential of the spices alone. In conclusion, our
      results demonstrate that the cognitive impairment caused by exposure to cold can
      be effectively countered by agents with thermogenic potential.

PMID- 30208749
TI  - Histone methyl-transferases and demethylases in the autophagy regulatory network:
      the emerging role of KDM1A/LSD1 demethylase.
AB  - Macroautophagy/autophagy is a physiological mechanism that is essential for the
      maintenance of cellular homeostasis and stress adaptation. Defective autophagy is
      associated with many human diseases, including cancer and neurodegenerative
      disorders. The emerging implication of epigenetic events in the control of the
      autophagic process opens new avenues of investigation and offers the opportunity
      to develop novel therapeutic strategies in diseases associated with dysfunctional
      autophagy-lysosomal pathways. Accumulating evidence reveals that several
      methyltransferases and demethylases are essential regulators of autophagy, and
      recent studies have led to the identification of the lysine demethylase
      KDM1A/LSD1 as a promising drug target. KDM1A/LSD1 modulates autophagy at multiple
      levels, participating in the transcriptional control of several downstream
      effectors. This review summarizes our current understanding of the role of
      KDM1A/LSD1 in the autophagy regulatory network.

PMID- 30208751
TI  - Telemedicine in long-term care of glaucoma patients.
AB  - Introduction This manuscript describes data from an original study, simulating a
      tele-glaucoma programme in an established clinic practice with an
      interdisciplinary team. This is a 'real life' trial of a telemedicine approach to
      see a follow-up patient. The goal is to evaluate the accuracy of such a programme
      to detect worsening and/or unstable disease. Such a programme is attractive since
      in-clinic time could be reduced for both the patient and provider. This study
      evaluates agreement between in-person and remote assessment of glaucoma
      progression. Methods A total of 200 adult glaucoma patients were enrolled at a
      single institution. The in-person assessment by an optometrist or glaucoma
      specialist at time of enrolment was used as the gold standard for defining
      progression. Collated clinical data were then reviewed by four masked providers
      who classified glaucoma as progression or non-progression in each eye by
      comparing data from enrolment visit to data from the visit immediately prior to
      enrolment. Agreement of glaucoma progression between the masked observer and the
      in-person assessment was determined using Kappa statistics. Intra-observer
      agreement was calculated using Kappa to compare in-person to remote assessment
      when both assessments were performed by the same provider ( n = 279 eyes).
      Results A total of 399 eyes in 200 subjects were analysed. Agreement between in
      person versus remote assessment for the determination of glaucoma progression was
      63%, 62%, 69% and 68% for each reader 1-4 (kappa values = 0.19, 0.20, 0.35 and
      0.33, respectively). For intra-observer agreement, reader 1 agreed with their own
      in-person assessment for 65% of visits (kappa = 0.18). Discussion Intra-observer
      agreement was similar to the agreement for each provider who did not see the
      patient in person. This similarity suggests that telemedicine may be equally
      effective at identifying glaucomatous disease progression, regardless of whether
      the same provider performed both in-clinic and remote assessments. However, fair
      agreement levels highlight a limitation of using only telemedicine data to
      determine progression compared with clinical detail available during in-patient
      assessment.

PMID- 30208752
TI  - Macrodactyly: decision-making and surgery timing.
AB  - Macrodactyly is a rare condition in which fingers, hands or limb growth is
      unregulated, resulting in overgrowth of tissues in the affected extremities. It
      is critical to properly assess these extremities for signalling pathway,
      psychological impact and potential surgical intervention, to achieve the best
      possible outcome for each patient. Treatment approaches can vary, and patient and
      family expectations weigh heavily on care complexity. Common surgical procedures
      may include epiphysiodeses, osteotomies, debulking procedures, carpal tunnel
      releases, toe transfers and amputations. The selection and timing of these
      surgeries is a vital component of the approach, as delayed healing and excessive
      scarring may occur. The purpose of this review is to assist in the navigation of
      decision-making and surgical timing for patients presenting with overgrowth
      manifesting itself as macrodactyly.

PMID- 30208753
TI  - Priapism induced by various Psychotropics: A Case Series.
AB  - Priapism is a rare adverse effect of several psychotropics. Both, typical and
      atypical antipsychotics, as well as trazodone are known to cause priapism. The
      mechanism is still not fully understood, however, the most common assumption is
      that priapism occurs due to the alpha-adrenergic blocking effects of the drugs.
      Here we present from the AMSP database 19 cases of priapism being likely caused
      by a variety of psychotropics. We further reviewed case reports in order to find
      similaritie and to identify risk factors. Several patterns emerged: Common was
      the introduction of a specific drug to a patient resulting into the immediate
      development of priapism, as well as a change in drug plasma concentration due to
      a change of drug dosage or due to comedication with certain SSRIs. However,
      priapism can occur at nearly any age and with any dose. Clinicians must be aware
      of the risk and reports of early signs, such as prolonged erections, should be
      taken seriously.

PMID- 30208754
TI  - Predictive value of fasting blood glucose for serious coronary atherosclerosis in
      non-diabetic patients.
AB  - Objective To determine if high fasting blood glucose (FBG) level is an
      independent predictor of serious coronary lesions in patients with coronary
      artery disease (CAD). Methods We enrolled 64 patients who had symptoms of chest
      discomfort and who underwent coronary angiography. FBG was determined from blood
      samples and the extent of coronary artery lesions was analyzed according to
      Gensini score. We examined the relationships among diabetes, FBG, and coronary
      artery severity. Results Diabetes and FBG were significantly and positively
      related to Gensini score. Diabetes, but not FBG, was independently correlated
      with the occurrence of a Gensini score >41. However, FBG was significantly
      associated with Gensini score >41 in non-diabetic patients. Conclusion
      Hyperglycemia is an independent predictor of severe CAD in non-diabetic patients.
      Clinicians should be aware of this and should carry out appropriate early
      interventions.

PMID- 30208755
TI  - ClosureFast endovenous radiofrequency ablation for great saphenous vein and small
      saphenous vein incompetence. Efficacy and anatomical failure patterns.
AB  - Background Recurrence rates and patterns after endovenous radiofrequency ablation
      (ERFA) are poorly documented. Objective To assess the incidence and anatomical
      recurrence patterns of saphenous vein reflux after ERFA. Method Two hundred
      patients previously treated with ERFA were recalled for clinical assessment and
      venous-duplex ultrasound at three years post-treatment. Results A total of 106
      patients (68F, 38M) with a mean age of 49.4 years (SD +11.5y) were assessed. Mean
      follow-up was 42.1 months (SD + 20.1m). Further varicose veins were identified in
      31 patients (29.2%). Recanalization/recurrence/failure was diagnosed in 16
      patients (15.1%), including 18 trunks (8.7%), 13 great saphenous vein (6.3%) and
      5 small saphenous vein (2.4%). Twenty-seven patients (25%) developed neo
      incompetence in 31 trunks and 12 non-saphenous veins. All patients with truncal
      recanalization had a body mass index > 29 (range 29-42). Conclusion Disease
      progression was twice as high as the recanalization rate at three years post
      treatment using ERFA in this study. Raised body mass index may be a contributing
      factor; however, further longitudinal studies are required. Patient self
      selection bias may have also influenced our results.

PMID- 30208756
TI  - No Vertical Visual Field Asymmetry in Online Control: Evidence from Reaching in
      Depth.
AB  - We sought to determine whether a putative lower-visual field (loVF) advantage for
      projections to the visuomotor networks of the dorsal visual pathway influences
      online reaching control. Participants reached to 3-dimensional depth targets
      presented in the loVF and upper-visual field (upVF) in binocular and monocular
      visual conditions, and when online vision was available (i.e., closed-loop) or
      unavailable (i.e., open-loop). To examine the degree to which responses were
      controlled online we computed the proportion of variance (R2) explained by the
      spatial position of the limb at distinct stages in the reaching trajectory
      relative to a response's ultimate movement endpoint. Results showed that
      binocular and closed-loop reaches exhibited shorter movement times and more
      online corrections (i.e., smaller R2 values) than their monocular and open-loop
      counterparts. Notably, however, loVF and upper-visual field reaches exhibited
      equivalent performance metrics across all experimental conditions. Accordingly,
      results provide no evidence of a loVF advantage for online reaching control to 3
      dimensional targets.

PMID- 30208757
TI  - Autophagy regulates glucose-mediated root meristem activity by modulating ROS
      production in Arabidopsis.
AB  - Glucose produced from photosynthesis is a key nutrient signal regulating root
      meristem activity in plants; however, the underlying mechanisms remain poorly
      understood. Here, we show that, by modulating reactive oxygen species (ROS)
      levels, the conserved macroautophagy/autophagy degradation pathway contributes to
      glucose-regulated root meristem maintenance. In Arabidopsis thaliana roots, a
      short exposure to elevated glucose temporarily suppresses constitutive
      autophagosome formation. The autophagy-defective autophagy-related gene (atg)
      mutants have enhanced tolerance to glucose, established downstream of the glucose
      sensors, and accumulate less glucose-induced ROS in the root tips. Moreover, the
      enhanced root meristem activities in the atg mutants are associated with improved
      auxin gradients and auxin responses. By acting with AT4G39850/ABCD1 (ATP-binding
      cassette D1; Formerly PXA1/peroxisomal ABC transporter 1), autophagy plays an
      indispensable role in the glucose-promoted degradation of root peroxisomes, and
      the atg mutant phenotype is partially rescued by the overexpression of ABCD1.
      Together, our findings suggest that autophagy is an essential mechanism for
      glucose-mediated maintenance of the root meristem. Abbreviation: ABA: abscisic
      acid; ABCD1: ATP-binding cassette D1; ABO: ABA overly sensitive; AsA: ascorbic
      acid; ATG: autophagy related; CFP: cyan fluorescent protein; Co-IP: co
      immunoprecipitation; DAB: 3',3'-diaininobenzidine; DCFH-DA: 2',7'
      dichlorodihydrofluorescin diacetate; DR5: a synthetic auxin response element
      consists of tandem direct repeats of 11 bp that included the auxin-responsive
      TGTCTC element; DZ: differentiation zone; EZ, elongation zone; GFP, green
      fluorescent protein; GSH, glutathione; GUS: beta-glucuronidase; HXK1: hexokinase
      1; H2O2: hydrogen peroxide; IAA: indole-3-acetic acid; IBA: indole-3-butyric
      acid; KIN10/11: SNF1 kinase homolog 10/11; MDC: monodansylcadaverine; MS:
      Murashige and Skoog; MZ: meristem zone; NBT: nitroblue tetrazolium; NPA: 1-N
      naphtylphthalamic acid; OxIAA: 2-oxindole-3-acetic acid; PIN: PIN-FORMED; PLT:
      PLETHORA; QC: quiescent center; RGS1: Regulator of G-protein signaling 1; ROS:
      reactive oxygen species; SCR: SCARECROW; SHR, SHORT-ROOT; SKL: Ser-Lys-Leu;
      SnRK1: SNF1-related kinase 1; TOR: target of rapamycin; UPB1: UPBEAT1; WOX5:
      WUSCHEL related homeobox 5; Y2H: yeast two-hybrid; YFP: yellow fluorescent
      protein.

PMID- 30208758
TI  - Placental Histology After Minor Trauma in Pregnancy: A Pilot Study.
AB  - Objective Trauma in pregnancy may cause placental abruption. Consequences of
      moderate placental injury on neurodevelopment are unknown. The aim was to
      evaluate placental histology after maternal trauma. Methods A prospective study
      was conducted at 2 tertiary medical centers in the Netherlands. Placentas from
      women exposed to maternal trauma >= 20 weeks' gestational age were histologically
      examined. Neurological follow-up of the infants was performed at 1 year of age by
      means of Alberta Infant Motor Scale. Histological findings were compared to
      placentas from pregnancies without trauma. Principal Results Thirteen placentas
      were investigated in the trauma group. The control group consisted of 15
      placentas. Placental pathology was seen more often in the trauma cases (11 of the
      13) than in the controls (6 of the 15), P = .024. Neurological follow-up was
      normal. Conclusions In this small population, majority of the placentas showed
      pathology after minor trauma in pregnancy without consequences for
      neurodevelopment at 1 year.

PMID- 30208759
TI  - How does estrogen work on autophagy?
AB  - : Macroautophagy/autophagy is vital for intracellular quality control and
      homeostasis. Therefore, careful regulation of autophagy is very important. In the
      past 10 years, a number of studies have reported that estrogenic effectors affect
      autophagy. However, some results, especially those regarding the modulatory
      effect of 17beta-estradiol (E2) on autophagy seem inconsistent. Moreover, several
      clinical trials are already in place combining both autophagy inducers and
      autophagy inhibitors with endocrine therapies for breast cancer. Not all patients
      experience benefit, which further confuses and complicates our understanding of
      the main effects of autophagy in estrogen-related cancer. In view of the
      importance of the crosstalk between estrogen signaling and autophagy, this review
      summarizes the estrogenic effectors reported to affect autophagy, subcellular
      distribution and translocation of estrogen receptors, autophagy-targeted
      transcription factors (TFs), miRNAs, and histone modifications regulated by E2.
      Upon stimulation with estrogen, there will always be opposing functional actions,
      which might occur between different receptors, receptors on TFs, TFs on autophagy
      genes, or even histone modifications on transcription. The huge signaling network
      downstream of estrogen can promote autophagy and reduce overstimulated autophagy
      at the same time, which allows autophagy to be regulated by estrogen in a
      restricted range. To help understand how the estrogenic regulation of autophagy
      affects cell fate, a hypothetical model is presented here. Finally, we discuss
      some exciting new directions in the field. We hope this might help to better
      understand the multiple associations between estrogen and autophagy, the
      pathogenic mechanisms of many estrogen-related diseases, and to design novel and
      efficacious therapeutics. ABBREVIATIONS: AP-1, activator protein-1; HATs, histone
      acetyltransferases; HDAC, histone deacetylases; HOTAIR, HOX transcript antisense
      RNA.

PMID- 30208760
TI  - Mir223 restrains autophagy and promotes CNS inflammation by targeting ATG16L1.
AB  - : Microglia are innate immune cells in the central nervous system (CNS), that
      supplies neurons with key factors for executing autophagosomal/lysosomal
      functions. Macroautophagy/autophagy is a cellular catabolic process that
      maintains cell balance in response to stress-related stimulation. Abnormal
      autophagy occurs with many pathologies, such as cancer, and autoimmune and
      neurodegenerative diseases. Hence, clarification of the mechanisms of autophagy
      regulation is of utmost importance. Recently, researchers presented microRNAs
      (miRNAs) as novel and potent modulators of autophagic activity. Here, we found
      that Mir223 deficiency significantly ameliorated CNS inflammation, demyelination
      and the clinical symptoms of experimental autoimmune encephalomyelitis (EAE) and
      increased resting microglia and autophagy in brain microglial cells. In contrast,
      the autophagy inhibitor 3-methylademine (3-MA) aggravated the clinical symptoms
      of EAE in wild-type (WT) and Mir223-deficienct mice. Furthermore, it was
      confirmed that Mir223 deficiency in mice increased the protein expression of
      ATG16L1 (autophagy related 16-like 1 [S. cerevisiae]) and LC3-II in bone marrow
      derived macrophage cells compared with cells from WT mice. Indeed, the cellular
      level of Atg16l1 was decreased in BV2 cells upon Mir223 overexpression and
      increased following the introduction of antagomirs. We also showed that the 3'
      UTR of Atg16l1 contained functional Mir223-responsive sequences and that
      overexpression of ATG16L1 returned autophagy to normal levels even in the
      presence of Mir223 mimics. Collectively, these data indicate that Mir223 is a
      novel and important regulator of autophagy and that Atg16l1 is a Mir223 target in
      this process, which may have implications for improving our understanding of the
      neuroinflammatory process of EAE. ABBREVIATIONS: 3-MA: 3-methylademine; ACTB/beta
      actin: actin, beta; ATG: autophagy related; ATG16L1: autophagy related 16-like 1
      (S. cerevisiae); BECN1: beclin 1, autophagy related; CNR2: cannabinoid receptor 2
      (macrophage); CNS: central nervous system; CQ: chloroquine; EAE: experimental
      autoimmune encephalomyelitis; FOXO3: forkhead box O3; GAPDH: glyceraldehyde-3
      phosphate dehydrogenase; H&E: hematoxylin and eosin; ITGAM: integrin alpha M;
      LPS: lipoplysaccharide; MAP1LC3/LC3: microtubule-associated protein 1 light chain
      3; miRNAs: microRNAs; MS: multiple sclerosis; PPARG: peroxisome proliferator
      activated receptor gamma; PTPRC: protein tyrosine phosphatase, receptor type, C;
      RA: rheumatoid arthritis; SQSTM1: sequestosome 1; TB: tuberculosis; TIMM23:
      translocase of inner mitochondrial membrane 23; TLR: toll-like receptor.

PMID- 30208762
TI  - NHS Scotland's community GP fellowship - a qualitative study of the first year.
AB  - NHS Scotland faces the challenges of an ageing population and a GP recruitment
      problem. Research has shown that hospital admissions can be reduced if community
      services can offer enhanced support, in keeping with the Scottish Government's
      2020 Vision for healthcare. This study presents the findings of an evaluation of
      the first year of a three-year community GP fellowship which included working in
      primary care and secondary care and an educational programme. A grounded theory
      approach was adopted with data collected from GP fellows and key stakeholders
      using focus groups and individual interviews. A total of 12 fellows were
      interviewed at various times in the first year and 22 key stakeholders were
      interviewed once. The main themes were: aspirations for the fellowship, career
      choices of recently-qualified GPs, perceptions of primary care and secondary care
      components, planning and preparation of educational events, the creation of
      community hubs and identity and status of fellows. The fellowship showed
      potential for a change in practice and was a good foundation for further
      collaboration between health care sectors. Physical hubs need to be constructed
      and resourced to allow fellows to demonstrate a reduction in hospital admissions.
      More research is needed throughout the lifetime of the fellowship.

PMID- 30208761
TI  - Feasibility and Preliminary Efficacy of a Teacher-Facilitated High-Intensity
      Interval Training Intervention for Older Adolescents.
AB  - PURPOSE: This study was designed to assess the feasibility and preliminary
      efficacy of a teacher-facilitated high-intensity interval training intervention
      for older adolescents (ie, 16-18 y). METHODS: Two secondary schools from New
      South Wales, Australia were recruited, and participants (ie, grade 11 students;
      16.2 [0.4] y) were randomized at the school level to the Burn 2 Learn
      intervention (n = 38), or a wait-list control group (n = 30). Teachers were
      trained to facilitate the delivery of the novel high-intensity interval training
      program, which involved 3 sessions per week (~12-20 min) for 14 weeks. A range of
      process measures were used to assess intervention feasibility (ie, recruitment,
      retention, attendance, and program satisfaction). Primary (cardiorespiratory
      fitness, determined using the progressive aerobic cardiovascular endurance run
      shuttle run test) and secondary outcomes were assessed at baseline and posttest
      (14-wk). RESULTS: Sixty-eight grade 11 students were recruited at baseline (85%
      of target sample), 61 participants completed posttest assessments (90% retention)
      and on average, participants performed 1.9 sessions per week. Overall, teachers
      (4.0/5) and students (4.0/5) were satisfied with the Burn 2 Learn program. Group
      by time effects were observed for cardioresp8iratory fitness (8.9 laps; 95%
      confidence intervals, 1.7-16.2) and a selection of secondary outcomes.
      CONCLUSION: This study provides evidence for the feasibility and preliminary
      efficacy of a teacher-facilitated high-intensity interval training intervention
      for older adolescents.

PMID- 30208764
TI  - Effectiveness of D-mannose, Hibiscus sabdariffa and Lactobacillus plantarum
      therapy in prevention of infectious events following urodynamic study.
AB  - INTRODUCTION AND AIM: The urodynamic study is an invasive examination that allows
      a thorough evaluation of the functional activity of the lower urinary tract
      (bladder, urethra). The execution of urodynamic study exposes the patient to the
      risk of contracting infections of the lower urinary tract. Prevention of urinary
      tract infections consists in the avoidance of risk factors and prophylaxis with
      antimicrobial and non-antimicrobial measures. In this article, we aimed to
      evaluate the effectiveness of a phytotherapeutic product composed of D-mannose,
      Hibiscus sabdariffa, and Lactobacillus plantarum in the prevention of infectious
      events following invasive urodynamic examination. MATERIALS AND METHODS: We
      selected 100 female consecutive patients (age 19-87 years) that underwent
      urodynamic invasive procedure. We prescribed 14-day therapy with D-mannose, H.
      sabdariffa, and L. plantarum to these 100 patients after urodynamic invasive
      test. After that, we have examined urine cultures and urinary symptoms through
      telephone interviews and hospital outpatient visits to evaluate the possible
      presence of urinary tract infections. RESULTS: Urinary tract infections were
      observed through urine culture in 13% of the selected patients; of the 13 urinary
      tract infections, 9 were observed in patients with urinary tract recurrent
      infections in the last year and the other 4 cases were associated with patients
      with no urinary infection in the last year. Three women reported some urinary
      symptoms and underwent antibiotic therapy. The other 10 cases were classified as
      asymptomatic bacteriuria. Three cases were related to patients presenting with
      pelvic organ prolapse. Eight cases were instead related to significant post
      voiding residue (>100). Six patients with urinary tract infection reported
      constipation in the last year. All patients completed the prescribed therapy due
      to the affordable price of the product and no side effects have been reported.
      CONCLUSION: Our study about the administration of D-mannose, H. sabdariffa, and
      L. plantarum after invasive urodynamic examination underlined how this
      phytotherapeutic product can reduce the risk of bacteriuria and urinary tract
      infection in women.

PMID- 30208765
TI  - Nutrition Label Use in a Latin American Middle-Income Country: Guatemala.
AB  - BACKGROUND: Obesity has become a major public health issue in Latin America.
      Nutrition labels have been proposed as 1 strategy to address the obesity epidemic
      as they may encourage consumers to reassess their choices at point-of-purchase.
      OBJECTIVE: We sought to determine the knowledge and stated use of the nutrition
      label in Guatemala. METHODS: Caregivers were randomly selected from public and
      private schools in Guatemala City. Caregivers were interviewed to assess
      knowledge and behaviors related to nutrition label use. Anthropometric
      measurements were measured using standardized procedures. Descriptive statistics
      and chi2 test were used to determine the differences between school types.
      RESULTS: Higher-income caregivers (88%) were more likely to be aware of nutrition
      labels, compared to those from low-income families (51%; P < .05). Furthermore,
      they were more likely to use it more frequently (42.2%) than their counterparts
      (18.3%; P = .03). Less than 50% of caregivers used nutrition labels for
      determining the amount of calories or nutritional content in a food portion, to
      compare nutrient content for different brands of the same food or to select
      products low in sugar, fat, and/or sodium. CONCLUSIONS: Our results provide
      evidence of the need to further explore nutritional label use and design that can
      better inform caregivers in Guatemala and other middle-income countries.
      Furthermore, given that the nutrition labels were for the most part rarely used
      by the participants in our study and that there are low literacy rates, other
      straightforward, easy-to-use strategies to communicate nutrition information at
      the point-of-sale could be useful to explore.

PMID- 30208763
TI  - The Application of Pupillometry in Hearing Science to Assess Listening Effort.
AB  - In recent years, the fields of Audiology and Cognitive Sciences have seen a
      burgeoning of research focusing on the assessment of the effort required during
      listening. Among approaches to this question, the pupil dilation response has
      shown to be an informative nonvolitional indicator of cognitive processing during
      listening. Currently, pupillometry is applied in laboratories throughout the
      world to assess how listening effort is influenced by various relevant factors,
      such as hearing loss, signal processing algorithms, cochlear implant
      rehabilitation, cognitive abilities, language competency, and daily-life hearing
      disability. The aim of this special issue is to provide an overview of the state
      of the art in research applying pupillometry, guidance for those considering
      embarking on pupillometry studies, and to illustrate the diverse ways in which it
      can be used to answer-and raise-pertinent research questions.

PMID- 30208767
TI  - Was It You . . . That You Left Behind?

PMID- 30208766
TI  - Commonly Consumed Foods: Nutritional Quality and Contributions to Recommended
      Nutrient Intakes of Schoolchildren in Rural Southeastern Nigeria.
AB  - BACKGROUND: Commonly consumed foods may be nutritionally inadequate.
      Schoolchildren may be at risk of undernutrition as a result of this. OBJECTIVE:
      To assess the nutrient and energy values of commonly consumed foods and determine
      their contributions to the recommended nutrient intakes (RNIs) of schoolchildren
      (6-15 years). METHODS: List of commonly consumed foods was obtained through focus
      group discussions with parents of schoolchildren. Ninety randomly selected
      schoolchildren were visited at home on 3 consecutive days (2 weekdays and 1
      weekend day) during which their portion sizes of these foods were obtained.
      Aliquots of these foods were collected, wrapped in polyethylene bags, and kept
      frozen until analysis. The samples were analyzed using standard methods.
      Percentage contributions of the nutrients to RNI were calculated. Data were
      analyzed by descriptive statistics. RESULTS: Results per 100 g showed that
      Pentaclethra macrophylla ( akpaka) sauce had the highest moisture (76.91%), ash
      (6.9%), iron (13.51%), and vitamin A (44.0 retinol equivalent [RE]). Steamed
      bambara groundnut pudding ( okpa) had the highest protein (15.08%). Maize +
      pigeon pea ( ayaraya oka) had the highest fat (15.76%). Tomato stew proved
      superior in carbohydrate (28.15%) and energy (194.6 kcal). Pterocarpus soyauxii (
      oha) soup contained the highest fiber (4.13%). Yam + pigeon pea ( ayaraya ji) had
      the highest zinc (4.97 mg). Contributions to RNI were protein (5.0%-134.0%),
      carbohydrate (0.6%-9.9%), energy (4.9%-38.8%), iron (1.5%-168.8%), vitamin A
      (0.0%-18.7%), and zinc (1.2%-166.0%). CONCLUSION: Most foods did not meet one
      third of the schoolchildren's RNI for vitamin A, zinc, iron, protein,
      carbohydrate, and energy. Nutrition education on nutrient adequacy is
      recommended.

PMID- 30208768
TI  - 2016-2017 Conferences.

PMID- 30208769
TI  - Addition of cyclosporine/tacrolimus for pediatric relapsed lupus nephritis during
      mycophenolate mofetil maintenance therapy.
AB  - Objective We aimed to evaluate the efficacy of low-dose cyclosporine (CsA) or
      tacrolimus (Tac) in children with proliferative lupus nephritis (PLN) during
      maintenance therapy. Methods A low dose of CsA or Tac was added to 11 children
      who relapsed during mycophenolate mofetil (MMF) maintenance therapy. Renal
      remission was analyzed at 3 and 6 months, and at 1, 2, and 3 years after CsA/Tac
      addition. Adverse effects were recorded. Results The clinical response rates were
      81.9%, 100%, 90.0%, 100%, and 100% at 3 months, 6 months, 1 year, 2 years, and 3
      years after CsA/Tac addition, respectively. Complete renal remission rates were
      45.5%, 45.5%, 40.0%, 44.4%, and 71.4% at 3 months, 6 months, 1 year, 2 years, and
      3 years after CsA/Tac addition, respectively. None of the patients had severe
      adverse events. Conclusion Low-dose CsA/Tac combined with MMF shows a promising
      effect in renal remission with acceptable safety in children with PLN. Therefore,
      this combination would be a good choice for children with lupus nephritis who
      relapse or have suboptimal MMF maintenance therapy.

PMID- 30208770
TI  - Conjugation of vitamin E-TPGS and guar gum to carry borneol for enhancing blood
      brain barrier permeability.
AB  - Herb borneol is usually used in clinics for the treatment of central nervous
      system illness, for its ability of blood-brain barrier permeability, although its
      poor water solubility and poor bioavailability limit its clinical application to
      some degree. In this study, we developed a novel nanoparticle combining the
      benefits of vitamin E d-alpha-tocopheryl poly(ethylene glycol) succinate (E-TPGS)
      (or TPGS) and guar gum to get TPGS-g-guar gum as a drug delivery system to carry
      borneol, which could improve the solubility of borneol and increase the drug
      loading capacity efficiently. The results showed that TPGS-g-guar gum
      nanoparticles delivery system was suitable to carry borneol and release the drug
      effectively, and TPGS-g-guar gum/borneol nanoparticles would be a potential
      platform for improving the treatment of central nervous system illness and
      cerebrovascular disease.

PMID- 30208772
TI  - Big Data: Data Science in Nursing.

PMID- 30208771
TI  - Big Data Cohort Extraction to Facilitate Machine Learning to Improve Statin
      Treatment.
AB  - Health care Big Data studies hold substantial promise for improving clinical
      practice. Among analytic tools, machine learning (ML) is an important approach
      that has been widely used by many industries for data-driven decision support. In
      Big Data, thousands of variables and millions of patient records are commonly
      encountered, but most data elements cannot be directly used to support decision
      making. Although many feature-selection tools can help identify relevant data,
      these tools are typically insufficient to determine a patient data cohort to
      support learning. Therefore, domain experts with nursing or clinic knowledge play
      critical roles in determining value criteria or the type of variables that should
      be included in the patient cohort to maximize project success. We demonstrate
      this process by extracting a patient cohort (37,506 individuals) to support our
      ML work (i.e., the production of a proactive strategy to prevent statin adverse
      events) from 130 million de-identified lives in the OptumLabsTM Data Warehouse.

PMID- 30208773
TI  - Midwest Nursing Research Society News.

PMID- 30208775
TI  - Transformational Leadership: A Model for Advanced Practice Holistic Nurses.

PMID- 30208776
TI  - Turning Words Into Action: Advancing the Role of Advanced Holistic Nurses.

PMID- 30208774
TI  - Discovering Public Health Nurse-Specific Family Home Visiting Intervention
      Patterns Using Visualization Techniques.
AB  - Visualization is a Big Data method for detecting and validating previously
      unknown and hidden patterns within large data sets. This study used visualization
      techniques to discover and test novel patterns in public health nurse (PHN)
      client-risk-intervention-outcome relationships. To understand the mechanism
      underlying risk reduction among high risk mothers, data representing complex
      social interventions were visualized in a series of three steps, and analyzed
      with other important contextual factors using standard descriptive and
      inferential statistics. Overall, client risk decreased after clients received
      personally tailored PHN services. Clinically important and unique PHN-client-risk
      intervention-outcome patterns were discovered through pattern detection using
      streamgraphs, heat maps, and parallel coordinates techniques. Statistical
      evaluation validated that PHN intervention tailoring leads to improved client
      outcomes. The study demonstrates the importance of exploring data to discover
      ways to improve care quality and client outcomes. Further research is needed to
      examine additional factors that may influence PHN-client-risk-intervention
      outcome patterns, and to test these methods with other data sets.

PMID- 30208777
TI  - Transformational Leadership: A Model for Advanced Practice Holistic Nurses.
AB  - Advanced Practice Holistic Nurse (APHN) leaders could provide a model of
      leadership to advance value based health care systems in the United States. The
      American Nurses Association has recognized Holistic Nursing as a specialty
      because of the emphasis placed on patient-centered care, the development of
      therapeutic relationships, interconnection, and holism. Transformational
      leadership is a framework that uses vision, inspiration and intellectual
      stimulation to motivate people toward needed change. The APHN is well positioned
      to use transformational leadership methods to lead teams placing the patient at
      the center of health care decision making and bring the essence of holism to the
      forefront of health care. Highlighted are methods for positive communication,
      inspiration, negotiation, and conflict resolution as tools the APHN could use to
      become a transformational leader. The purpose of this article is to discuss a
      framework for transformational leadership development and implementation to
      establish the holistic ideals of APHNs in the health care system.

PMID- 30208778
TI  - Guided Imagery for Pain Management in Postoperative Orthopedic Patients: An
      Integrative Literature Review.
AB  - BACKGROUND: Pain following orthopedic surgery can be intense due to the nature of
      the surgical procedure. Pain is a multilevel phenomenon that includes
      physiological and psychosocial components. Interventions that address body, mind,
      and spirit are needed to provide holistic management of pain. Guided imagery is a
      mind-body intervention that can address all aspects of the patient's pain
      experience. PURPOSE: This integrative review, informed by Watson's theory of
      human caring, identifies evidence that either supports or refutes the use of
      guided imagery as a supplement to pharmaceutical pain management for
      postoperative orthopedic patients. METHOD: An integrative literature search was
      conducted. Twenty-two studies were identified as potentially relevant to this
      study. Nine of the articles met all inclusion criteria and were included in this
      study. RESULTS AND CONCLUSIONS: Based on the evidence reviewed, it is recommended
      that guided imagery be used as an adjunct for pain management in patients
      undergoing orthopedic surgery. However, additional research in this area is
      needed. Future research: Two topics for further research were identified. The
      first is a need to identify an optimal frequency of use of guided imagery. The
      second is to identify how to ensure patients are using the intervention as
      recommended.

PMID- 30208780
TI  - Assessing Standing Long Jump Developmental Levels Using an Inertial Measurement
      Unit.
AB  - This study tested the feasibility of using an inertial measurement unit to
      discriminate different developmental levels of children performing the standing
      long jump (SLJ). Sixty-four children (54.6% boys, 46.4% girls) aged 8 to 11 years
      old ( M = 9.17, SD = 0.97) performed the SLJ three times and were classified by
      rater observations into three developmental levels. Concurrently, they wore an
      inertial measurement unit from which a set of temporal and kinematic parameters
      for the quantitative assessment of their jumps. A multivariate analysis of
      variance revealed that variability among the developmental groups was identified
      by the overall set of parameters, while discriminant function analysis verified
      that these parameters discriminated among developmental levels. Primary
      predictors for developmental group discrimination were maximum peak acceleration
      in the vertical and anteroposterior directions, respectively, and normalized
      preparation time. These outcomes represent significant steps toward improving the
      assessment of SLJ rate of development in childhood and supporting physical
      education.

PMID- 30208779
TI  - Effect of Gum Chewing Frequency on Oxygenation of the Prefrontal Cortex.
AB  - Since increased cerebral oxygenation reflects cerebral activation, this study
      investigated the effect of mastication frequency on prefrontal cortex
      oxygenation. Eleven young volunteers (nine women, two men; M age = 20.9 years, SD
      = 0.9) carried out three trials in which they were asked to chew a tasteless gum
      for 3 min at varying (rates of mastication frequency: 30, 70, and 110). Breaks of
      2 min each were interleaved between trials. The oxygenation of the left
      prefrontal cortex was monitored by near-infrared spectroscopy. We found a
      significant increase in cortical oxygenation during gum chewing in all three
      conditions ( p < .05), compared with a resting level; we also found a significant
      difference between the Fast and Slow chewing conditions, and between the Fast and
      Normal (70 rpm) conditions, both findings seemingly related to activation of a
      motor command in frontal brain regions. To our knowledge, this is the first
      report on the effect of mastication frequency on cerebral oxygenation. Possible
      implications of this finding are discussed.

PMID- 30208781
TI  - Human-Human Handover Tasks and How Distance and Object Mass Matter.
AB  - We investigated the coordination between two individuals during object handovers.
      Ten participants (eight males, two females; 26.0 +/- 5.0 years, 72.7 +/- 13.5 kg,
      1.73 +/- 0.8 m) arranged in pairs (a giver and a receiver), passed an object from
      the giver to the receiver at a self-selected speed. A motion capture system
      quantified the giver and the receiver's motion simultaneously. Three
      interpersonal distances and three object masses were chosen to study the
      handover. We hypothesized that (a) the handover occurs at half of the
      interpersonal distance between the giver and receiver and (b) the handover height
      depends on the objects' mass. Taken together, our results show that the handover
      strongly depends on the interpersonal distance between the giver and receiver,
      while object mass related only to handover duration.

PMID- 30208783
TI  - Organizational Identity Safety Cue Transfers.
AB  - Traditionally, researchers have focused on identity-congruent safety cues such as
      the effect of gender diversity awards on women's sense of inclusion in
      organizations. The present studies investigate, for the first time, whether
      identity safety cues (e.g., organizational diversity structures) aimed at one
      stigmatized group transfer via perceptions of the organization's ideology (social
      dominance orientation), resulting in identity safety for individuals with
      stigmatized identities incongruent with the cue. Across four studies, we
      demonstrate that White women experience identity safety from organizational
      diversity structures aimed at racial minorities (Studies 1 and 2), and men of
      color experience identity safety from organizational diversity structures aimed
      at women (Study 3). Furthermore, while White men similarly perceive the
      organization's ideology, this does not promote identity safety (Study 4). Thus,
      we argue that individuals view organizations commended for diversity as promoting
      more egalitarian attitudes broadly, resulting in the transference of identity
      safety cues for stigmatized individuals.

PMID- 30208782
TI  - The synthetic glycolipid-based TLR4 antagonist FP7 negatively regulates in vitro
      and in vivo haematopoietic and non-haematopoietic vascular TLR4 signalling.
AB  - TLRs, including TLR4, have been shown to play a crucial role in cardiovascular
      inflammatory-based diseases. The main goal of this study was to determine the
      potential of FP7, a synthetic glycolipid active as a TLR4 antagonist, to modulate
      haematopoietic and non-haematopoietic vascular TLR4 pro-inflammatory signalling.
      HUVEC, human THP-1 monocytes, THP-1-derived macrophages, mouse RAW-264.7
      macrophages and Angiotensin II-infused apolipoprotein E-deficient mice were in
      vitro and in vivo models, respectively. Western blotting, Ab array and ELISA
      approaches were used to explore the effect of FP7 on TLR4 functional activity in
      response to bacterial LPS ( in vitro) and endogenous ligands of sterile
      inflammation ( in vitro and in vivo). Following activation of TLR4, in vitro and
      in vivo data revealed that FP7 inhibited p38 MAPK and p65 NF-kB phosphorylation
      associated with down-regulation of a number of TLR4-dependent pro-inflammatory
      proteins. In addition to inhibition of LPS-induced TLR4 signalling, FP7
      negatively regulated TLR4 activation in response to ligands of sterile
      inflammation (hydroperoxide-rich oxidised LDL, in vitro and Angiotensin II
      infusion, in vivo). These results demonstrate the ability of FP7 to negatively
      regulate in vitro and in vivo haematopoietic and non-haematopoietic vascular TLR4
      signalling both in humans and mice, suggesting the potential therapeutic use of
      this TLR4 antagonist for pharmacological intervention of vascular inflammatory
      diseases.

PMID- 30208784
TI  - Midwest Nursing Research Society News.

PMID- 30208787
TI  - Perspectives on Neuroscience and Behavior.

PMID- 30208785
TI  - To Submit, or Resubmit, That Is the Question.

PMID- 30208790
TI  - Requiring Authorship Competence Among PhD Students.

PMID- 30208791
TI  - Midwest Nursing Research Society News.

PMID- 30208788
TI  - Neuroanatomical Substrates for Risk Behavior.
AB  - Individuals vary substantially in their tendency to take risks. In the past two
      decades, a large number of neuroimaging studies in humans have explored the
      neural mechanisms of several cognitive processes that contribute to risk taking.
      In this article, I focus on functional and structural MRI studies that
      investigated uncertainty processing, one of the main features of risk behavior.
      Using decision-making and learning paradigms, these studies implicated a network
      of brain areas, including posterior parietal cortex, anterior insula, anterior
      cingulate cortex, and ventrolateral prefrontal cortex, in various aspects of
      uncertainty processing. Individual differences in behavior under uncertainty are
      reflected in the function and structure of some of these areas and are integrated
      into value representations in ventromedial prefrontal cortex and ventral
      striatum, reinforcing the potential contribution of all of these brain structures
      to individual tendencies to take risks.

PMID- 30208792
TI  - Recent Advances in Pancreatic Surgery.

PMID- 30208793
TI  - Persistent Pain After Wrist or Hand Fracture: Development and Validation of a
      Prognostic Model.
AB  - Study Design Secondary analysis of a prospective cohort study. Background
      Worldwide, the incidence of wrist fracture is increasing. There are currently no
      externally validated prognostic models to inform early decision making for these
      patients. Objectives To develop and validate a prognostic model from a
      comprehensive range of candidate prognostic factors that can identify patients at
      risk of developing persistent pain following wrist or hand fracture. Methods We
      developed and validated a prognostic model using secondary data derived from a
      prospective cohort study (n=715) with recruitment sites in three metropolitan
      hospitals in Sydney, Australia. The primary outcome was persistent pain four
      months following the injury. We used a backwards stepwise regression analysis to
      develop the model in two hospitals (n=408) and externally validate it in a third
      hospital (n=307). To determine the accuracy of the model we assessed calibration
      and discrimination in accordance with the PROGRESS framework. Results Complete
      data were available for 95% of the cohort. Out of 14 candidate variables, the
      final model contained two prognostic factors: patient age and pain intensity
      reported at initial presentation. The area under the receiver operating curve
      statistic was 0.63 (95% CI 0.56 - 0.69) in the development sample, and 0.61 (95%
      CI 0.51 - 0.70) in the validation sample. The model systematically overestimated
      risk (intercept = -1.13, slope = 0.73). Conclusion We developed and externally
      validated a prognostic model to predict persistent pain four months after a wrist
      or hand fracture. Future studies are needed to assess whether the accuracy of
      this model can be improved by updating and validating it in local settings. Level
      of Evidence Prognosis, level 1b. J Orthop Sports Phys Ther, Epub 12 Sep 2018.
      doi:10.2519/jospt.2019.8342.

PMID- 30208794
TI  - Blood Flow Restricted Resistance Exercise as a Post-Orthopedic Surgery
      Rehabilitation Modality: A Review of Venous Thromboembolism Risk.
AB  - Synopsis Restoration of skeletal muscle mass and strength are critical to
      successful outcomes following orthopedic surgery. Blood flow restricted
      resistance exercise (BFR) has emerged as an attractive candidate to augment
      traditional low intensity physical rehabilitation exercise, and has yielded
      successful outcomes over a wide variety of applications. BFR is well tolerated
      and safe for the majority of individuals, though the post-surgical orthopedic
      patient has additional considerations due to their heightened risk for venous
      thromboembolism (VTE). While the pathogenesis of VTE is multifactorial and
      individual specific, it is commonly described as a combination of blood stasis,
      endothelial injury, and alterations in the constituents of the blood leading to
      hypercoagulability. The collective literature suggests that, given the pathogenic
      mechanisms of VTE, the finite use of a wide, partially occluding cuff during
      resistance exercise should be low risk and that the likelihood of BFR directly
      causing a VTE event is remote. Alternatively, it is plausible that BFR may
      enhance blood flow and promote fibrinolysis. Of greater concern would be the
      individual with preexisting asymptomatic VTE, which could be dislodged during
      BFR. Though, it is unknown if the direct risk associated with BFR is greater than
      the risk associated with traditional exercise alone. Presently, there are no
      universally agreed upon standards indicating which post-surgical orthopedic
      patients may perform BFR safely. While excluding all post-surgical orthopedic
      patients from performing BFR may be overly precautious, clinicians need to
      thoroughly screen for VTE signs and symptoms, be cognizant of each patient's risk
      factors, and use proper equipment and prescriptions methods prior to initiating
      BFR. J Orthop Sports Phys Ther, Epub 12 Sep 2018. doi:10.2519/jospt.2019.8375.

PMID- 30208795
TI  - Exploratory Study of 6-month Pain Trajectories in Individuals With Predominant
      Patellofemoral Osteoarthritis: A Cohort Study.
AB  - Study Design Prospective longitudinal cohort study. Background Knowledge of
      patellofemoral (PF) osteoarthritis (OA) pain trajectories is vital for clinicians
      and patients to make disease-specific decisions regarding treatment options and
      tailor coping strategies. Objectives To describe pain trajectories of people
      living with PF OA presenting to a chronic care management program. Second, to
      explore baseline characteristics associated with different trajectories. Methods
      Eighty-eight participants presenting to a chronic care management program
      reported their worst pain over the previous week at baseline, 6, 12, 18 and 26
      weeks using a 10-cm visual analogue scale. Trajectories (classes) were identified
      using latent class growth analysis. Demographics, pain, physical performance,
      strength, quality of life, mental health and lower limb/foot structural measures
      obtained at baseline were assessed for association with trajectory class
      membership. Results Class 1 (28%) exhibiting high persistent pain from baseline
      (6.8cm +/- 1.7cm), and persisting through time (p=0.52). Class 2 (57%) exhibited
      moderate baseline pain (4.8cm +/- 1.7cm), which also remained persistent
      (p=0.97). Individuals in class 3 (15%) exhibited low improving pain (baseline
      pain: 2.6cm +/- 1.2cm) through time (p=0.017). Baseline measures of poor Knee
      injury and Osteoarthritis Outcome Scores, local and proximal sensitivity to
      pressure and weaker knee extensors were associated with increased odds (range:
      1.03 (1.0, 1.07) to 16.24 (2.53, 104.34)) of following the high pain trajectory.
      Conclusion In people with PF OA presenting to a chronic care management program,
      distinct pain trajectories appear to exist. Baseline variables may be useful for
      identifying individuals at risk of poorer prognosis. Larger studies are needed to
      confirm such utility. Level of Evidence Prognosis, Level 2b. J Orthop Sports Phys
      Ther, Epub 12 Sep 2018. doi:10.2519/jospt.2019.8354.

PMID- 30208797
TI  - Association of serum gamma-glutamyltransferase with chronic kidney disease risk:
      a meta-analysis.
AB  - Studies on the association between gamma-glutamyltransferase (GGT) and chronic
      kidney disease (CKD) have produced conflicting results. This study aimed to
      investigate the association of elevated GGT with the risk of CKD in the adult
      general population by performing a meta-analysis of relevant articles. We
      searched PubMed, Web of Science, and Embase databases from their inception to
      October 2017 to identify observational studies regarding the association between
      serum GGT level and CKD. Pooled risk ratio (RR) and 95% confidence intervals (CI)
      was calculated as the effective measures. Eight studies with 116 011 individuals
      were included in this meta-analysis. Overall, individuals with the highest versus
      the lowest GGT level were not associated with an increased risk of CKD (RR 1.14;
      95% CI 0.99-1.31). Subgroup analysis showed that the pooled RR for the highest
      versus the lowest GGT category was 1.31 (95% CI 1.06-1.60) for the Asian
      countries and 1.04 (95% CI 0.88-1.23) for the Western countries. In the sex
      stratified analysis, no significant associations of elevated GGT with risk of CKD
      were found for both women (RR 0.95; 95% CI 0.84-1.07) and men (RR 1.08; 95% CI
      0.86-1.36). This meta-analysis demonstrates no significant association between
      elevated serum GGT and risk of CKD in the adult general population. However,
      future well-designed studies are needed to evaluate the impact of geographical
      region on the association.

PMID- 30208796
TI  - Non-Radiographic Measurement of Hallux Valgus Angle Using Self-Photography.
AB  - Background The reference standard of hallux valgus angle measurement is to use
      radiographs of the feet. However, its availability is constrained due to cost and
      radiation exposure. Less invasive non-radiographic assessments have been
      proposed. However, a measurement using self-photography has not been reported.
      Objectives To determine 1) the reliability of hallux valgus angle measurement
      using the same photographs of the feet (pHVA), 2) the reliability of repeated
      self-photography trials, and 3) the measurement error when the radiographic
      hallux valgus ankle (rHVA) was estimated using pHVA. Methods Participants took
      photographs of their own feet using a digital camera. The intra- and interrater
      reliability of pHVA measurements was assessed using intraclass correlation
      coefficient (ICC) and 95% minimum detectable change (MDC). The participants took
      photographs twice, and the reliability of repeated self-photography trials was
      examined. Participants also received radiographs of their feet from which the
      rHVA was measured. The measurement error was assessed using the mean difference
      and 95% limits of agreement. Results The intra- and interrater ICC of pHVA
      measurement was 0.98, with the MDCs less than 2 degrees . The ICC of pHVA
      measurement for repeated self-photography was 0.96, and the MDC was 6.9 degrees .
      pHVA was systematically lower than the rHVA by 5.3 degrees . Conclusion
      Measurement of pHVA using self-photography was reproducible, although pHVA
      underestimated rHVA. pHVA can be a useful non-radiographic method to quantify
      hallux valgus deformity. J Orthop Sports Phys Ther, Epub 12 Sep 2018.
      doi:10.2519/jospt.2019.8280.

PMID- 30208798
TI  - Melatonin protects against myocardial ischemia-reperfusion injury by elevating
      Sirtuin3 expression and manganese superoxide dismutase activity.
AB  - Myocardial ischemia-reperfusion (MI/R) injury is a crucial cause for mortality
      throughout the world. Recent studies indicated that melatonin might exert
      profound cardio-protective effect in MI/R injury. However, the underlying
      mechanisms are not completely understood. In the current study, we aimed to
      explore the potential effect of melatonin in the pathological process of MI/R.
      Both in vivo MI/R model and in vitro H9c2 cell line simulated I/R (SIR) model
      were applied with or without melatonin supplementation. We found that Sirtuin3
      (Sirt3) expression and activity were markedly decreased under MI/R and SIR
      conditions. Melatonin treatment significantly increased myocardial Sirt3
      expression, and alleviated MI/R-induced cardiac morphology changes and cardiac
      dysfunction, as well as myocardial apoptosis level. In addition, DHE and JC-1
      staining results demonstrated that melatonin reduced mitochondrial reactive
      oxygen species (ROS) generation and restored ATP production after SIR injury via
      elevating Sirt3 expression. By using siRNA targeting Sirt3, we confirmed that the
      beneficial effects of melatonin were dependent on Sirt3, which in turn
      deacetylated and activated manganese superoxide dismutase (MnSOD). Collectively,
      the current study demonstrated the protective effect of melatonin against MI/R
      injury via alleviating myocardial oxidative stress. Moreover, these beneficial
      effects were associated with the deacetylation modification of Sirt3 on MnSOD.

PMID- 30208801
TI  - Corrigendum.

PMID- 30208799
TI  - Effect of treatment with oral Ca boluses following calving on concentrations of
      Ca in serum in pasture-based dairy cows.
AB  - AIMS To assess the effect of the administration of two oral Ca boluses on
      concentrations of total Ca, beta-hydoxybutyrate (BHB) and non-esterified fatty
      acids (NEFA) in serum, and urine pH, in recently calved pasture-fed dairy cows.
      METHODS Friesian or Friesian cross Jersey cows from one dairy farm were blocked
      by age and randomly assigned to no treatment (control; n=14), or treatment (n=13)
      with two oral Ca boluses administered approximately 12 hours apart, with the
      first bolus being given within 14 hours of calving. Each bolus weighed 198 g and
      contained 43 g of Ca; 31 g of Ca from calcium chloride and 12 g of Ca from
      calcium sulfate. Cows were enrolled over three calendar days, and all cows were
      managed in one group during the 24-hour study period. Blood samples were
      collected at 0, 1, 2, 4, 8, 12, 13, 14, 16, 20 and 24 hours after the initial
      treatment. Serum from each time point was analysed for concentrations of total
      Ca, and from 0, 12, and 24 hours for NEFA and BHB. Urine was collected at 0, 12
      and 24 hours for pH measurement and pH was categorised as <7 or >=7. The effect
      of treatment on percentage change in concentrations of Ca in serum relative to 0
      hours, and concentrations of NEFA, BHB and urine pH, was examined using
      multivariable repeated measures mixed models with cow as a random effect. RESULTS
      In the final multivariable model for percentage change in concentrations of Ca,
      there was an interaction between time and treatment (p=0.004), with the
      percentage increase being higher in treatment than control cows at 1, 2, 4, 8 and
      13 hours. At 12 hours, 5/13 (41%) treated cows had a urine pH <7compared to 0/12
      (0%) control cows (p<0.001), and at 24 hours 13/13 (100%) treated cows had urine
      pH <7 compared to 0/12 (0%) control cows (p<0.001). Over the 24-hour period, mean
      concentrations of NEFA or BHB in serum were similar in treated and control cows
      (p>0.3). CONCLUSIONS AND CLINICAL RELEVANCE Oral treatment with two Ca boluses
      increased concentrations of total Ca in serum and decreased urine pH in pasture
      fed cows. This bolus has the potential to reduce the prevalence and duration of
      subclinical hypocalcaemia in recently calved cows.

PMID- 30208802
TI  - Comparing Different Methods to Create a Linear Model for Uncontrolled Manifold
      Analysis.
AB  - An essential step in uncontrolled manifold analysis is creating a linear model
      that relates changes in elemental variables to changes in performance variables.
      Such linear models are usually created by means of an analytical method. However,
      a multiple regression analysis is also suggested. Whereas the analytical method
      includes only averages of joint angles, the regression method uses the
      distribution of all joint angles. We examined whether the latter model is more
      suitable to describe manual reaching movements. The relation between estimated
      and measured fingertip-position deviations from the mean of individual trials,
      the relation between fingertip variability and nongoal-equivalent variability,
      goal-equivalent variability, and nongoal-equivalent variability indicated that
      the linear model created with the regression method gives a more accurate
      description of the reaching data. Therefore, we suggest the usage of the
      regression method to create the linear model for uncontrolled manifold analysis
      in tasks that require the approximation of the linear model.

PMID- 30208803
TI  - New insight in the biological integration of polytetrafluoroethylene from an
      explant used for diaphragm repair.
AB  - Congenital diaphragmatic hernia is a severe disease requiring diaphragm
      replacement mostly with expanded polytetrafluoroethylene. Unfortunately, the
      recurrence rate is high due to prosthesis failure with significant morbidity for
      the child. To provide a better understanding of the integration and possible
      failure processes of the biomaterial implanted in humans, we conducted electron
      microscopical and mechanical assessments on a prosthesis explant from a child
      with congenital diaphragmatic hernia presenting a recurrence. Our findings show a
      major penetration of connective tissue into the expanded polytetrafluoroethylene
      on the rough side, whereas the smooth side presents few tissue colonization. This
      penetration is more important in the central area (area A) with large collagen
      bundles and layers, in comparison to the peripheral areas without prosthesis
      failure (area B), where few extracellular matrix is produced. The connective
      tissue penetrates the prosthesis in depth. In contrast, the peripheral areas with
      prosthesis failure (area C) show very few cells and extracellular matrix, with an
      oriented organization in comparison to areas A and B. Obviously, the forces
      applied on the implanted material modulate the cellular behavior of the newly
      developed tissues. Atomic force microscopic measurements of the biomaterials'
      surfaces may explain some cellular behaviors according to areas with or without
      failure.

PMID- 30208805
TI  - Understanding drug release from PCL/gelatin electrospun blends.
AB  - Electrospinning is one of the efficient processes to fabricate polymeric fibrous
      scaffolds for several biomedical applications. Several studies have published to
      demonstrate drug release from electrospun scaffolds. Blends of natural and
      synthetic electrospun fibers provide excellent platform to combine mechanical and
      bioactive properties. Drug release from polymer blends is a complex process. Drug
      release from polymer can be dominated by one or more of following mechanisms:
      polymer erosion, relaxation, and degradation. In this study, electrospun
      polycaprolactone (PCL)-gelatin blends are investigated to understand release
      mechanism of Rhodamine B dye. Also, this article summarizes the effect of high
      pressure carbon dioxide on drug loading and release from PCL-gelatin fibers.
      Results indicate that release media diffusion is a dominant mechanism for PCL
      gelatin electrospun fibers. Thickness of electrospun mat becomes critical for
      blends with gelatin. As gelatin is highly soluble in water and has tendency of
      gelation, it affects diffusion of release media in and out of scaffold. This
      article is a key step forward in understanding release from electrospun blends.

PMID- 30208804
TI  - The effect of REDV/TiO2 coating coronary stents on in-stent restenosis and re
      endothelialization.
AB  - The coronary artery stent has been widely used in clinic. In-stent restenosis was
      mainly caused by the excessive proliferation of smooth muscle cell and the
      inflammation due to the metal ion released from stent scaffold of the drug
      eluting stent. Thus, to reduce the in-stent restenosis and promote the vascular
      endothelialization have become a hot research point in this area. In this paper,
      a nano-TiO2 ceramic coating was deposited on 316L stainless steel to reduce the
      metal ion release and to inhibit the inflammation reaction. An endothelia cell
      selective adhesion peptide Arg-Glu-Asp-Val (REDV) coating was prepared on the
      ceramic coating by a polydopamine technology to promote the endothelialization.
      The corrosion test indicated that nano-TiO2 ceramic film could effectively
      decrease the nickel ion released from 316L stainless steel. REDV/TiO2 coating
      could promote the endothelial cell adhesion and proliferation, meanwhile
      REDV/TiO2 coating could also increase the nitric oxide concentration. Bare metal
      stent, TiO2-coated stent and REDV/TiO2-coated stent were implanted in the iliac
      arteries of rabbit model. In-stent restenosis and re-endothelialization were
      evaluated at 28 days post-implantation of the stents. The results showed that
      REDV/TiO2-coated stents could effectively reduce in-stent restenosis and promote
      re-endothelialization in comparison with TiO2-coated drug-eluting stent and bare
      metal stent. These results suggest that REDV/TiO2-coated drug-eluting stent maybe
      a good choice of the application for coronary artery disease.

PMID- 30208806
TI  - Osteoinduction of stem cells by collagen peptide-immobilized hydrolyzed
      poly(butylene succinate)/beta-tricalcium phosphate scaffold for bone tissue
      engineering.
AB  - Bone substitute is a therapeutic approach to treat bone abnormalities. A scaffold
      serves mainly as osteoconductive elements. To facilitate a better biological
      performance, short collagen peptide was immobilized onto hydrolyzed poly(butylene
      succinate)/beta-tricalcium phosphate (HPBSu/TCP) scaffolds. PBSu/TCP (80:20)
      scaffolds were fabricated by a supercritical CO2 technique, hydrolyzed with 0.6 M
      NaOH and conjugated with short collagen peptide tagged with or without red
      fluorescence. The surface morphology and porous structure of scaffolds were
      characterized by scanning electron microscopy and micro-computed tomography.
      Human mesenchymal stem cells were cultured onto the scaffolds and examined for
      osteogenic differentiation and biomineralization in vitro by means of alkaline
      phosphatase activity, alizarin red staining, and reverse transcription-polymerase
      chain reaction. The PBSu/TCP and HPBSu/TCP scaffolds were successfully prepared.
      Scanning electron microscopy and micro-computed tomography results showed that
      the porosity was distributed throughout the scaffolds with the pore sizes in the
      range of 250-900 um. Fluorescence microscopy demonstrated retention of tagged
      short collagen peptide on the scaffold. Mesenchymal stem cells adhered and grew
      well on the material. Under osteogenic induction, cells cultured on the short
      collagen peptide -immobilized scaffold significantly produced a greater amount of
      alkaline phosphatase activity and positive mineralization than those cultured on
      the control scaffold. The present results have shown that the short collagen
      peptide-immobilized HPBSu/TCP scaffold enhanced osteoinduction and
      biomineralization of stem cell-derived osteoblasts, possibly via stimulation of
      alkaline phosphatase activity. This suggests the potential use of osteogenic
      peptide-immobilized material in bone tissue engineering for correcting bone
      defects.

PMID- 30208807
TI  - Fabrication of Zn-Sr-doped laser-spinning glass nanofibers with antibacterial
      properties.
AB  - The morphology and dimensions of bioactive materials are essential attributes to
      promote tissue culture. Bioactive materials with nanofibrous structure have
      excellent potential to be used as bone-defect fillers, since they mimic the
      collagen in the extracellular matrix. On the other hand, bioactive glasses with
      applications in regenerative medicine may present antibacterial properties, which
      depend on glass composition, concentration and the microorganisms tested.
      Likewise, their morphology may influence their antibacterial activity too. In the
      present work, the laser-spinning technique was used to produce bioactive glass
      nanofibers of two different compositions: 45S5 Bioglass(r) and ICIE16M, bioactive
      glass doped with zinc and strontium. Their antibacterial activity against
      Staphylococcus aureus was tested by culturing them in dynamic conditions.
      Bacterial growth index profiles during the first days of experiment can be
      explained by the variations in the pH values of the media. The bactericidal
      effect of the doped nanofibers at longer times is justified by the release of
      zinc and strontium ions. Cytotoxicity was analyzed by means of cell viability
      tests performed with BALB/3T3 cell line.

PMID- 30208808
TI  - President's Message.

PMID- 30208809
TI  - A Year in Review.

PMID- 30208810
TI  - Offering Hope to Caregivers is a Transcultural Nursing Opportunity.

PMID- 30208813
TI  - Kidney donation and transplantation in Australia: more than a supply and demand
      equation.

PMID- 30208814
TI  - Automatic reporting of estimated glomerular filtration rate in Australia turns
      13: re-examining the impact.

PMID- 30208815
TI  - Massive oxidative haemolysis and renal failure caused by high dose vitamin C.

PMID- 30208816
TI  - Accreditation as a quality improvement tool: is it still relevant?

PMID- 30208817
TI  - Protecting our children from obesity: challenges and opportunities.

PMID- 30208818
TI  - Disparity of access to kidney transplantation by Indigenous and non-Indigenous
      Australians.
AB  - OBJECTIVE: To compare the likelihood of Indigenous and non-Indigenous Australians
      being placed on the waiting list for transplantation of a kidney from a deceased
      donor; to compare the subsequent likelihood of transplantation. DESIGN, SETTING
      AND PARTICIPANTS: Observational cohort study; analysis of data from the Australia
      and New Zealand Dialysis and Transplant (ANZDATA) Registry for patients aged 18
      60 years at the start of renal replacement therapy, who commenced renal
      replacement therapy in Australia between 28 June 2006 and 31 December 2016. MAIN
      OUTCOME MEASURES: Time to wait-listing; time to kidney transplantation after wait
      listing. RESULTS: 10 839 patients met the inclusion criteria, of whom 2039 (19%)
      were Indigenous Australians; 217 Indigenous and 3829 non-Indigenous patients were
      active on the waiting list at least once during the study period. The hazard
      ratio (HR) for wait-listing (Indigenous v non-Indigenous patients, adjusted for
      patient- and disease-related factors) in the first year of renal replacement
      therapy varied with age and remoteness (range, 0.11 [95% CI, 0.07-0.15] to 0.36
      [95% CI, 0.16-0.56]); in subsequent years the adjusted HR was 0.90 (95% CI, 0.50
      1.6). The adjusted HR for transplantation during the first year of wait-listing
      did not differ significantly from 1.0; for subsequent years of wait-listing,
      however, the adjusted HR was 0.40 (95% CI, 0.29-0.55). CONCLUSION: Disparities
      between Indigenous and non-Indigenous patients with end-stage kidney disease in
      access to kidney transplantation are not explained by patient- or disease-related
      factors. Changes in policy and practice are needed to reduce these differences.

PMID- 30208819
TI  - Contemporary approaches to the prevention and management of paediatric obesity:
      an Australian focus.
AB  - Of the 34 member countries of the Organisation for Economic Co-operation and
      Development, obesity prevalence is highest in the United States, with Australia
      ranking fifth for girls and eighth for boys. Curbing the problem is achievable
      and can be realised through a combination of smart governance across many
      sectors, community initiatives, the support of individual efforts, and clinical
      leadership. At 5 years of age, one in five Australian children are already
      affected by overweight or obesity; obesity prevention strategies must therefore
      start before this age. There is strong evidence that reducing screen time and
      promoting breastfeeding in 0-2-year-olds are effective interventions in the early
      years. The main behavioural risk factors for obesity are overconsumption of
      energy-dense, nutrient-poor foods and a lack of physical activity. Emerging
      evidence suggests poor sleep quality and duration and high amounts of sedentary
      time also play a role. Systems-based policy actions may change long term obesity
      prevalence in children by targeting the food environment through nutrition
      labelling, healthy foods in schools, restricted unhealthy food marketing to
      children, and fiscal policies to reduce consumption of harmful foods and sugar
      sweetened beverages. Macro-environmental factors influence obesity risk. Public
      transport policy and the built environment (proximity to parks, bike paths, green
      space, schools and shops) influence play time spent outdoors, walking and
      cycling. Greater access to parks and playgrounds and active commuting are
      associated with lower body mass index. Australian interventions have largely
      employed individual level approaches. These are important, but of limited
      effectiveness unless priority is also given to policies that reduce obesity
      conducive environments. Clinicians can provide anticipatory guidance to support
      healthy weight and weight-related behaviours, including weight monitoring, early
      feeding and children's diets, physical activity opportunities, and limited
      sedentary and screen time. Investigations in children with obesity usually
      include liver function tests and measuring fasting glucose, lipid and possibly
      insulin levels. As obesity can be associated with micronutrient deficiencies, it
      may be prudent to check full blood count and iron, vitamin B12 and vitamin D
      levels. Endocrinological assessment is usually not needed. Second line
      investigations may include liver ultrasound, oral glucose tolerance testing and
      sleep study. Traditional treatment of child and adolescent obesity has focused on
      family-based, multicomponent (diet, physical activity and behaviour change)
      interventions, although these lead to small and often short term weight
      reductions (mean, - 1.45 kg; 95% CI, 1.88 to - 1.02). Nevertheless, these
      principles remain core interventions in children and adolescents with obesity. A
      very low energy diet should be considered in adolescents with severe obesity or
      obesity-related comorbidities, and for adolescents who have not achieved weight
      loss following a more conventional dietary approach. Pharmacotherapy confers only
      small reductions in weight; for example, effect size for metformin is - 3.90 kg
      (95% CI, - 5.86 to - 1.94). Bariatric surgery should be considered in adolescents
      over 15 years of age with severe obesity (body mass index > 40 kg/m<sup>2</sup>,
      or > 35 kg/m<sup>2</sup> in the presence of severe complications).

PMID- 30208820
TI  - When to initiate dialysis for end-stage kidney disease: evidence and challenges.
AB  - The decision about when to start dialysis for end-stage kidney disease (ESKD) is
      complex and is influenced by many factors. ESKD-related symptoms and signs are
      the most common indications for dialysis initiation. Creatinine-based formulae to
      estimate glomerular filtration rate (GFR) are inaccurate in patients with ESKD
      and, thus, the decision to start dialysis should not be based solely on estimated
      GFR (eGFR). Early dialysis initiation (ie, at an eGFR > 10 mL/min/1.73
      m<sup>2</sup>) is not associated with a morbidity and mortality benefit, as shown
      in the Initiating Dialysis Early and Late (IDEAL) study. This observation has
      been incorporated into the latest guidelines, which place greater emphasis on the
      assessment of patients' symptoms and signs rather than eGFR. It is suggested that
      in asymptomatic patients with stage 5 chronic kidney disease, dialysis may be
      safely delayed until the eGFR is at least as low as 5-7 mL/min/1.73 m<sup>2</sup>
      if there is careful clinical follow-up and adequate patient education. The
      decision on when to start dialysis is even more challenging in older patients.
      Due to their comorbidities and frailty, dialysis initiation may be associated
      with worse outcomes and quality of life. Therefore, the decision to start
      dialysis in these patients should be carefully weighed against its risks, and
      conservative care should be considered in appropriate cases. To optimise the
      decision-making process for dialysis initiation, patients need to be referred to
      a nephrologist in a timely fashion to allow adequate pre-dialysis care and
      planning. Dialysis initiation and its timing should be a shared decision between
      physician, patients and family members, and should be tailored to the individual
      patient's needs.

PMID- 30208821
TI  - Voluntary assisted dying: time to consider the details.

PMID- 30208823
TI  - "Accidental" GP helping the homeless.

PMID- 30208822
TI  - Adverse effects of modified release oxycodone/naloxone in patients with moderate
      to severe liver impairment.

PMID- 30208824
TI  - Around the universities and research institutes.

PMID- 30208826
TI  - Translation Factor eIF5A, Modification with Hypusine and Role in Regulation of
      Gene Expression. eIF5A as a Target for Pharmacological Interventions.
AB  - Translation factor eIF5A participates in protein synthesis at the stage of
      polypeptide chain elongation. Two eIF5A isoforms are known that are encoded by
      related genes whose expression varies significantly in different tissues. The
      eIF5A1 isoform is a constitutively and ubiquitously expressed gene, while the
      eIF5A2 isoform is expressed in few normal tissues and is an oncogene by a number
      of parameters. Unique feature of eIF5A isoforms is that they are the only two
      proteins that contain amino acid hypusine. Modification with hypusine is critical
      requirement for eIF5A activity. Another distinctive feature of eIF5A is its
      involvement in the translation of only a subset of the total population of cell
      mRNAs. The genes for which mRNAs translation requires eIF5A are the members of
      certain functional groups and are involved in cell proliferation, apoptosis,
      inflammatory processes, and regulation of transcription and RNA metabolism. The
      involvement of eIF5A is necessary for the translation of proteins containing
      oligoproline fragments and some other structures. Modification of eIF5A by
      hypusine is implemented by two highly specialized enzymes, deoxyhypusine synthase
      (DHS) and deoxyhypusine hydroxylase (DOHH), which are not involved in other
      biochemical reactions. Intracellular activity of these enzymes is closely
      associated with systems of protein acetylation, polyamine metabolism and other
      biochemical processes. Inhibition of DHS and DOHH activity provides the
      possibility of pharmacological control of eIF5A activity and expression of eIF5A
      dependent genes.

PMID- 30208827
TI  - Immunotropic Effects and Proposed Mechanism of Action for 3-Hydroxy-3
      methylglutaryl-coenzyme A Reductase Inhibitors (Statins).
AB  - Inhibitors of HMG-CoA reductase (statins) are the major group of lipid-lowering
      drugs. Along with hypocholesterolemic activity, statins exhibit anti-inflammatory
      and immunomodulatory properties that expand their clinical use, particularly, in
      the treatment of chronic inflammatory and autoimmune disorders. In this review,
      we critically analyze the data of statin effects on immune cells (e.g., monocytes
      and T cells) involved in the development of atherosclerosis and other chronic
      inflammatory diseases. We (i) discuss the properties of statins and routes of
      cell entry, as well as their major intracellular targets; (ii) evaluate the data
      on the effects of statins on the subset composition of circulatory monocytes,
      ability of monocytes to migrate to the site of inflammation (cell motility and
      expression of adhesion molecules and chemokine receptors), production of
      cytokines, matrix metalloproteinases, and reactive oxygen species by
      monocytes/macrophages, and antigen-presenting activity in peripheral blood
      monocyte-derived dendritic cells; and (iii) summarize the data on the regulation
      of proliferation and differentiation of various CD4+ T cell subsets (type 1/2/17
      helper T cells and regulatory T cells) by statins.

PMID- 30208828
TI  - Biochemistry of Direct Cell-Cell Interactions. Signaling Factors Regulating
      Orchestration of Cell Populations.
AB  - Biochemical mechanisms for the orchestration of cell populations are discussed in
      view of direct cell-cell interactions and composition of the intercellular
      medium. In our works of the last 20 years, we used circahoralian (ultradian)
      rhythm of protein synthesis as a marker of cell interactions. Experiments in cell
      cultures are described; some influences on the organism native medium were
      performed. Information is presented on the signaling membrane factors that
      trigger a cascade of processes in the cytoplasm and lead to the orchestration of
      cell activity in vitro and in vivo. Among these factors are blood serum
      neurotransmitters, gangliosides, and some hormones. Studying protein synthesis
      kinetics allowed us to understand the importance of maintaining the constant
      levels of signaling factors in mammalian blood. The literature on protein
      phosphorylation as a key process of cell organization is reviewed. The
      persistence of the organizing signal for several days is described as a type of
      cell "memory". It seems promising to extend the area for application of direct
      cell-cell interactions (respiration of cells, proliferation, etc.) to study
      possibilities of epigenetic regulation. It is important to continue the studies
      on the mechanisms of biochemical action of the known drugs as signaling factors.

PMID- 30208829
TI  - Structure and Function of Multidrug Resistance Protein 1.
AB  - This review considers one of the most clinically relevant representatives of the
      ABC transporters - multidrug resistance protein 1 (P-glycoprotein 1 or Pgp). Data
      on the primary, secondary, and tertiary structure of the protein, its synthesis
      and degradation, and roles of its fragments in transporter activity are
      presented. Particular attention is given to the mechanism of functioning of Pgp.
      In view of the absence of a generally recognized mechanism of action of Pgp,
      several existing models of the protein transport cycle are discussed. Epigenetic
      regulation of the ABCB1 gene and modulation of Pgp expression by microRNAs are
      discussed.

PMID- 30208830
TI  - Structural Alterations in Human Fibroblast Growth Factor Receptors in
      Carcinogenesis.
AB  - Fibroblast growth factor (FGF) plays an important role in human embryogenesis,
      angiogenesis, cell proliferation, and differentiation. Carcinogenesis is
      accompanied by aberrant constitutive activation of FGF receptors (FGFRs)
      resulting from missense mutation in the FGFR1-4 genes, generation of chimeric
      oncogenes, FGFR1-4 gene amplification, alternative splicing shift toward
      formation of mesenchymal FGFR isoforms, and FGFR overexpression. Altogether,
      these alterations contribute to auto- and paracrine stimulation of cancer cells
      and neoangiogenesis. Certain missense mutations are found at a high rate in
      urinary bladder cancer and can be used for non-invasive cancer recurrence
      diagnostics by analyzing urine cell pellet DNA. Chimeric FGFR1/3 and amplified
      FGFR1/2 genes can predict cell response to the targeted therapy in various
      oncological diseases. In recent years, high-throughput sequencing has been used
      to analyze exomes of virtually all human tumors, which allowed to construct
      phylogenetic trees of clonal cancer evolution with special emphasis on driver
      mutations in FGFR1-4 genes. At present, FGFR blockers, such as multi-kinase
      inhibitors, specific FGFR inhibitors, and FGF ligand traps are being tested in
      clinical trials. In this review, we discuss current data on the functioning of
      the FGFR family proteins in both normal and cancer cells, mutations in the FGFR1
      4 genes, and mechanisms underlying their oncogenic potential, which might be
      interesting to a broad range of scientists searching for specific tumor markers
      and targeted anti-cancer drugs.

PMID- 30208832
TI  - Inorganic Polyphosphate and Cancer.
AB  - This review presents data on the relationship between inorganic polyphosphate
      metabolism and carcinogenesis including participation of polyphosphates in the
      regulation of activity of mTOR and other proteins involved in carcinogenesis, the
      role of h-prune protein (human polyphosphatase) in cell migration and metastasis
      formation, the prospects for using polyphosphates and inhibitors of polyphosphate
      metabolism enzymes as agents for controlling cell proliferation and migration.

PMID- 30208831
TI  - Essential Light Chains of Myosin and Their Role in Functioning of the Myosin
      Motor.
AB  - This review summarizes current data on the structure and functions of myosin
      essential light chains (ELCs) and on their role in functioning of the myosin head
      as a molecular motor. The data on structural and functional features of the N
      terminal extension of myosin ELC from skeletal and cardiac muscles are analyzed;
      the role of this extension in the ATP-dependent interaction of myosin heads with
      actin in the molecular mechanism of muscle contraction is discussed. The data on
      possible interactions of the ELC N-terminal extension with the myosin head motor
      domain in the myosin ATPase cycle are presented, including the results of the
      authors' studies that are in favor of such interactions.

PMID- 30208834
TI  - Amphipathic CRAC-Containing Peptides Derived from the Influenza Virus A M1
      Protein Modulate Cholesterol-Dependent Activity of Cultured IC-21 Macrophages.
AB  - Entry of many viral and bacterial pathogens into host cells depends on
      cholesterol and/or cholesterol-enriched domains (lipid rafts) in the cell
      membrane. Earlier, we showed that influenza virus A matrix protein M1 contains
      amphipathic alpha-helices with exposed cholesterol-recognizing amino acid
      consensus (CRAC) motifs. In order to test possible functional activity of these
      motifs, we studied the effects of three synthetic peptides corresponding to the
      CRAC-containing alpha-helices of the viral M1 protein on the phagocytic activity
      of cultured mouse IC-21 macrophages. The following peptides were used:
      LEVLMEWLKTR (M1 alpha-helix 3, a.a. 39-49; further referred to as peptide 1),
      NNMDKAVKLYRKLK (M1 alpha-helix 6, a.a. 91-105; peptide 2), and GLKNDLLENLQAYQKR
      (M1 alpha-helix 13, a.a. 228-243; peptide 3). We found that all three peptides
      modulated interactions of IC-21 macrophages with non-opsonized 2-um target
      particles. The greatest effect was demonstrated by peptide 2: in the presence of
      35 MUM peptide 2, the phagocytic index of IC-21 macrophages exceeded the control
      value by 60%; 10-11 mM methyl-beta-cyclodextrin abolished this effect. Peptides 1
      and 3 exerted weak inhibitory effect in a narrow concentration range of 5-10 MUM.
      The dose-response curves could be approximated by a sum of two (stimulatory and
      inhibitory) components with different Hill coefficients, suggesting existence of
      at least two peptide-binding sites with different affinities on the cell surface.
      CD spectroscopy confirmed that the peptides exhibit structural flexibility in
      solutions. Altogether, our data indicate that amphipathic CRAC-containing
      peptides derived from the viral M1 protein modulate lipid raft-dependent
      processes in IC-21 macrophages.

PMID- 30208833
TI  - Glutathionylation of Na,K-ATPase Alpha-Subunit Alters Enzyme Conformation and
      Sensitivity to Trypsinolysis.
AB  - We found earlier that Na,K-ATPase is purified from duck salt glands in partially
      glutathionylated state (up to 13 of the 23 cysteine residues of the Na,K-ATPase
      catalytic alpha-subunit can be S-glutathionylated). To determine the effect of
      glutathionylation on the enzyme conformation, we have analyzed the products of
      trypsinolysis of Na,K-ATPase alpha-subunit in different conformations with
      different extent of glutathionylation. Incubation of the protein in the E1
      conformation with trypsin produced a large fragment with a molecular mass (MM) of
      80 kDa with the following formation of smaller fragments with MM 40, 35.5, and 23
      kDa. Tryptic digestion of Na,K-ATPase in the E2 conformation also resulted in the
      generation of the fragments with MM 40, 35.5, and 23 kDa. Deglutathionylation of
      Na,K-ATPase alpha-subunit increases the rate of proteolysis of the enzyme in both
      E1 and E2 conformations. The pattern of tryptic digestion of the alpha-subunit in
      E2 conformation additionally glutathionylated with oxidized glutathione is
      similar to that of partially deglutathionylated Na,K-ATPase. The pattern of
      tryptic digestion of the additionally glutathionylated alpha-subunit in E1
      conformation is similar to that of the native enzyme. The highest rate of
      trypsinolysis was observed for the alpha-subunit in complex with ouabain (E2-OBN
      conformation). Additional glutathionylation increased the content of high
      molecular-weight fragments among the digestion products, as compared to the
      native and deglutathionylated enzymes. The data obtained were confirmed using
      molecular modeling that revealed that number of sites accessible for
      trypsinolysis is higher in the E2P-OBN conformation than in the E1- and E2
      conformations and that glutathionylation decreases the number of sites accessible
      for trypsin. Therefore, glutathionylation affects enzyme conformation and its
      sensitivity to trypsinolysis. The mechanisms responsible for the changes in the
      Na,K-ATPase sensitivity to trypsinolysis depending on the level of enzyme
      glutathionylation and increase in the enzyme sensitivity to proteolysis upon its
      binding to ouabain, as well as physiological role of these phenomena are
      discussed.

PMID- 30208835
TI  - Laccase-Catalyzed Heterocoupling of Dihydroquercetin and p-Aminobenzoic Acid:
      Effect of the Reaction Product on Cultured Cells.
AB  - Derivatization of the natural flavonoid dihydroquercetin with p-aminobenzoic acid
      was carried out in an ethyl acetate/citric buffer biphasic system using laccase
      from the fungus Trametes hirsuta. The main reaction product yield was ~68 mol %.
      The product was characterized by 1H NMR, 13C NMR, and liquid chromatography-mass
      spectroscopy, and its structure was elucidated. The reaction product affected
      viability of cultured human rhabdomyosarcoma cells (RD cell line) in a dose
      dependent manner and, therefore, can be of interest to pharmaceutical industry.

PMID- 30208836
TI  - Effects of the Linear Fragments of Beta-(1->3)-Glucans on Cytokine Production in
      vitro.
AB  - Beta-glucans, homopolysaccharides composed of 3,6-branching beta-(1->3)-D-glucan
      chains, attract great interest as inducers of cytokine synthesis. In this work,
      we studied the ability of linear fragments of beta-glucan chains to activate
      cytokine synthesis. Synthetic nona-beta-(1->3)-D-glucoside (SO) representing a
      linear fragment of beta-glucan chain, endotoxin (ED), and natural beta-(1->3)-D
      glucan (GL) were tested for their role as inducers of cytokines in whole
      peripheral blood cultures collected from 17 individuals. The concentrations of IL
      12p70, IFN-gamma, IL-2, IL-10, IL-8, IL-6, IL-4, IL-5, IL-1beta, TNF-alpha, and
      TNF-beta were measured in the supernatants after 2, 24, and 48 h of cell
      culturing. SO, ED, and GL stimulated production of pro-inflammatory IFN-gamma, IL
      1beta, IL-2, IL-6, IL-8, TNF-alpha and anti-inflammatory IL-10. The highest
      levels of biosynthesis after stimulation with SO were registered for IL-6, IL-8,
      and TNF-alpha. SO stimulated production of all cytokines (except IFN-gamma) to a
      lesser extent than ED and GL. The IFN-gamma/IL-10 (Th1/Th2) ratios after 24 and
      48 h of culturing were 3.1 and 7.5 for SO; 0.03 and 0.1 for GL; and 0.06 and 0.2
      for ED, respectively. The results indicate that linear fragments of beta-glucans
      cause a more pronounced shift of immune response towards the pro-inflammatory
      (Th1) type than beta-glucan itself.

PMID- 30208838
TI  - GeFaST: An improved method for OTU assignment by generalising Swarm's fastidious
      clustering approach.
AB  - BACKGROUND: Massive genomic data sets from high-throughput sequencing allow for
      new insights into complex biological systems such as microbial communities.
      Analyses of their diversity and structure are typically preceded by clustering
      millions of 16S rRNA gene sequences into OTUs. Swarm introduced a new clustering
      strategy which addresses important conceptual and performance issues of the
      popular de novo clustering approach. However, some parts of the new strategy,
      e.g. the fastidious option for increased clustering quality, come with their own
      restrictions. RESULTS: In this paper, we present the new exact, alignment-based
      de novo clustering tool GeFaST, which implements a generalisation of Swarm's
      fastidious clustering. Our tool extends the fastidious option to arbitrary
      clustering thresholds and allows to adjust its greediness. GeFaST was evaluated
      on mock-community and natural data and achieved higher clustering quality and
      performance for small to medium clustering thresholds compared to Swarm and other
      de novo tools. Clustering with GeFaST was between 6 and 197 times as fast as with
      Swarm, while the latter required up to 38% less memory for non-fastidious
      clustering but at least three times as much memory for fastidious clustering.
      CONCLUSIONS: GeFaST extends the scope of Swarm's clustering strategy by
      generalising its fastidious option, thereby allowing for gains in clustering
      quality, and by increasing its performance (especially in the fastidious case).
      Our evaluations showed that GeFaST has the potential to leverage the use of the
      (fastidious) clustering strategy for higher thresholds and on larger data sets.

PMID- 30208837
TI  - Genomic insights into host adaptation between the wheat stripe rust pathogen
      (Puccinia striiformis f. sp. tritici) and the barley stripe rust pathogen
      (Puccinia striiformis f. sp. hordei).
AB  - BACKGROUND: Plant fungal pathogens can rapidly evolve and adapt to new
      environmental conditions in response to sudden changes of host populations in
      agro-ecosystems. However, the genomic basis of their host adaptation, especially
      at the forma specialis level, remains unclear. RESULTS: We sequenced two isolates
      each representing Puccinia striiformis f. sp. tritici (Pst) and P. striiformis f.
      sp. hordei (Psh), different formae speciales of the stripe rust fungus P.
      striiformis highly adapted to wheat and barley, respectively. The divergence of
      Pst and Psh, estimated to start 8.12 million years ago, has been driven by high
      nucleotide mutation rates. The high genomic variation within dikaryotic
      urediniospores of P. striiformis has provided raw genetic materials for genome
      evolution. No specific gene families have enriched in either isolate, but
      extensive gene loss events have occurred in both Pst and Psh after the divergence
      from their most recent common ancestor. A large number of isolate-specific genes
      were identified, with unique genomic features compared to the conserved genes,
      including 1) significantly shorter in length; 2) significantly less expressed; 3)
      significantly closer to transposable elements; and 4) redundant in pathways. The
      presence of specific genes in one isolate (or forma specialis) was resulted from
      the loss of the homologues in the other isolate (or forma specialis) by the
      replacements of transposable elements or losses of genomic fragments. In
      addition, different patterns and numbers of telomeric repeats were observed
      between the isolates. CONCLUSIONS: Host adaptation of P. striiformis at the forma
      specialis level is a complex pathogenic trait, involving not only virulence
      related genes but also other genes. Gene loss, which might be adaptive and driven
      by transposable element activities, provides genomic basis for host adaptation of
      different formae speciales of P. striiformis.

PMID- 30208839
TI  - Genome-wide markers reveal a complex evolutionary history involving divergence
      and introgression in the Abert's squirrel (Sciurus aberti) species group.
AB  - BACKGROUND: Genetic introgression between divergent lineages is now considered
      more common than previously appreciated, with potentially important consequences
      for adaptation and speciation. Introgression is often asymmetric between
      populations and patterns can vary for different types of loci (nuclear vs.
      organellar), complicating phylogeographic reconstruction. The taxonomy of the
      ecologically specialized Abert's squirrel species group has been controversial,
      and previous studies based on mitochondrial data have not fully resolved the
      evolutionary relationships among populations. Moreover, while these studies
      identified potential areas of secondary contact between divergent lineages, the
      possibility for introgression has not been tested. RESULTS: We used RAD-seq to
      unravel the complex evolutionary history of the Abert's squirrel species group.
      Although some of our findings reinforce inferences based on mitochondrial data,
      we also find significant areas of discordance. Discordant signals generally arise
      from previously undetected introgression between divergent populations that
      differentially affected variation at mitochondrial and nuclear loci. Most
      notably, our results support earlier claims (disputed by mitochondrial data) that
      S. aberti kaibabensis, found only on the north rim of the Grand Canyon, is highly
      divergent from other populations. However, we also detected introgression of S.
      aberti kaibabensis DNA into other S. aberti populations, which likely accounts
      for the previously inferred close genetic relationship between this population
      and those south of the Grand Canyon. CONCLUSIONS: Overall, the evolutionary
      history of Abert's squirrels appears to be shaped largely by divergence during
      periods of habitat isolation. However, we also found evidence for interbreeding
      during periods of secondary contact resulting in introgression, with variable
      effects on mitochondrial and nuclear markers. Our results support the emerging
      view that populations often diversify under scenarios involving both divergence
      in isolation and gene flow during secondary contact, and highlight the value of
      genome-wide datasets for resolving such complex evolutionary histories.

PMID- 30208840
TI  - The caseinolytic protease complex component CLPC1 in Arabidopsis maintains
      proteome and RNA homeostasis in chloroplasts.
AB  - BACKGROUND: Homeostasis of the proteome is critical to the development of
      chloroplasts and also affects the expression of certain nuclear genes. CLPC1
      facilitates the translocation of chloroplast pre-proteins and mediates protein
      degradation. RESULTS: We found that proteins involved in photosynthesis are
      dramatically decreased in their abundance in the clpc1 mutant, whereas many
      proteins involved in chloroplast transcription and translation were increased in
      the mutant. Expression of the full-length CLPC1 protein, but not of the N
      terminus-deleted CLPC1 (DeltaN), in the clpc1 mutant background restored the
      normal levels of most of these proteins. Interestingly, the DeltaN
      complementation line could also restore some proteins affected by the mutation to
      normal levels. We also found that that the clpc1 mutation profoundly affects
      transcript levels of chloroplast genes. Sense transcripts of many chloroplast
      genes are up-regulated in the clpc1 mutant. The level of SVR7, a PPR protein, was
      affected by the clpc1 mutation. We showed that SVR7 might be a target of CLPC1 as
      CLPC1-SVR7 interaction was detected through co-immunoprecipitation. CONCLUSION:
      Our study indicates that in addition to its role in maintaining proteome
      homeostasis, CLPC1 and likely the CLP proteasome complex also play a role in
      transcriptome homeostasis through its functions in maintaining proteome
      homeostasis.

PMID- 30208841
TI  - Comparative transcriptome analysis reveals that tricarboxylic acid cycle-related
      genes are associated with maize CMS-C fertility restoration.
AB  - BACKGROUND: C-type cytoplasmic male sterility (CMS-C) is one of the three major
      types of cytoplasmic male sterility (CMS) in maize. Rf4 is a dominant restorer
      gene for CMS-C and has great value in hybrid maize breeding, but little
      information concerning its functional mechanism is known. RESULTS: To reveal the
      functional mechanism of Rf4, we developed a pair of maize near-isogenic lines
      (NILs) for the Rf4 locus, which included a NIL_rf4 male-sterile line and a
      NIL_Rf4 male fertility-restored line. Genetic analysis and molecular marker
      detection indicated that the male fertility of NIL_Rf4 was controlled by Rf4.
      Whole-genome sequencing demonstrated genomic differences between the two NILs was
      clustered in the Rf4 mapping region. Unmapped reads of NILs were further
      assembled to uncover Rf4 candidates. RNA-Seq was then performed for the
      developing anthers of the NILs to identify critical genes and pathways associated
      with fertility restoration. A total of 7125 differentially expressed genes (DEGs)
      were identified. These DEGs were significantly enriched in 242 Gene Ontology (GO)
      categories, wherein 100 DEGs were involved in pollen tube development, pollen
      tube growth, pollen development, and gametophyte development. Homology analysis
      revealed 198 male fertility-related DEGs, and pathway enrichment analysis
      revealed that 58 DEGs were enriched in cell energy metabolism processes involved
      in glycolysis, the pentose phosphate pathway, and pyruvate metabolism. By
      querying the Plant Reactome Pathway database, we found that 14 of the DEGs were
      involved in the mitochondrial tricarboxylic acid (TCA) cycle and that most of
      them belonged to the isocitrate dehydrogenase (IDH) and oxoglutarate
      dehydrogenase (OGDH) enzyme complexes. Transcriptome sequencing and real-time
      quantitative PCR (qPCR) showed that all the above TCA cycle-related genes were up
      regulated in NIL_Rf4. The results of our subsequent enzyme-linked immunosorbent
      assay (ELISA) experiments pointed out that the contents of both the IDH and OGDH
      enzymes accumulated more in the spikelets of NIL_Rf4 than in those of NIL_rf4.
      CONCLUSION: The present research provides valuable genomic resources for deep
      insight into the molecular mechanism underlying CMS-C male fertility restoration.
      Importantly, our results indicated that genes involved in energy metabolism,
      especially some mitochondrial TCA cycle-related genes, were associated with maize
      CMS-C male fertility restoration.

PMID- 30208843
TI  - A genome wide survey reveals multiple nematocyst-specific genes in Myxozoa.
AB  - BACKGROUND: Myxozoa represents a diverse group of microscopic endoparasites whose
      life cycle involves two hosts: a vertebrate (usually a fish) and an invertebrate
      (usually an annelid worm). Despite lacking nearly all distinguishing animal
      characteristics, given that each life cycle stage consists of no more than a few
      cells, molecular phylogenetic studies have revealed that myxozoans belong to the
      phylum Cnidaria, which includes corals, sea anemones, and jellyfish. Myxozoa,
      however, do possess a polar capsule; an organelle that is homologous to the
      stinging structure unique to Cnidaria: the nematocyst. Previous studies have
      identified in Myxozoa a number of protein-coding genes that are specific to
      nematocytes (the cells producing nematocysts) and thus restricted to Cnidaria.
      Determining which other genes are also homologous with the myxozoan polar capsule
      genes could provide insight into both the conservation and changes that occurred
      during nematocyst evolution in the transition to endoparasitism. RESULTS:
      Previous studies have examined the phylogeny of two cnidarian-restricted gene
      families: minicollagens and nematogalectins. Here we identify and characterize
      seven additional cnidarian-restricted genes in myxozoan genomes using a
      phylogenetic approach. Four of the seven had never previously been identified as
      cnidarian-specific and none have been studied in a phylogenetic context. A
      majority of the proteins appear to be involved in the structure of the nematocyst
      capsule and tubule. No venom proteins were identified among the cnidarian
      restricted genes shared by myxozoans. CONCLUSIONS: Given the highly divergent
      forms that comprise Cnidaria, obtaining insight into the processes underlying
      their ancient diversification remains challenging. In their evolutionary
      transition to microscopic endoparasites, myxozoans lost nearly all traces of
      their cnidarian ancestry, with the one prominent exception being their
      nematocysts (or polar capsules). Thus nematocysts, and the genes that code for
      their structure, serve as rich sources of information to support the cnidarian
      origin of Myxozoa.

PMID- 30208844
TI  - Web of microbes (WoM): a curated microbial exometabolomics database for linking
      chemistry and microbes.
AB  - BACKGROUND: As microbiome research becomes increasingly prevalent in the fields
      of human health, agriculture and biotechnology, there exists a need for a
      resource to better link organisms and environmental chemistries. Exometabolomics
      experiments now provide assertions of the metabolites present within specific
      environments and how the production and depletion of metabolites is linked to
      specific microbes. This information could be broadly useful, from comparing
      metabolites across environments, to predicting competition and exchange of
      metabolites between microbes, and to designing stable microbial consortia. Here,
      we introduce Web of Microbes (WoM; freely available at: http://webofmicrobes.org
      ), the first exometabolomics data repository and visualization tool. DESCRIPTION:
      WoM provides manually curated, direct biochemical observations on the changes to
      metabolites in an environment after exposure to microorganisms. The web interface
      displays a number of key features: (1) the metabolites present in a control
      environment prior to inoculation or microbial activation, (2) heatmap-like
      displays showing metabolite increases or decreases resulting from microbial
      activities, (3) a metabolic web displaying the actions of multiple organisms on a
      specified metabolite pool, (4) metabolite interaction scores indicating an
      organism's interaction level with its environment, potential for metabolite
      exchange with other organisms and potential for competition with other organisms,
      and (5) downloadable datasets for integration with other types of -omics
      datasets. CONCLUSION: We anticipate that Web of Microbes will be a useful tool
      for the greater research community by making available manually curated
      exometabolomics results that can be used to improve genome annotations and aid in
      the interpretation and construction of microbial communities.

PMID- 30208842
TI  - Comparative proteomic analysis of maize (Zea mays L.) seedlings under rice black
      streaked dwarf virus infection.
AB  - BACKGROUND: Maize rough dwarf disease (MRDD) is a severe disease that has been
      occurring frequently in southern China and many other Asian countries. MRDD is
      caused by the infection of Rice black streaked dwarf virus (RBSDV) and leads to
      significant economic losses in maize production. To well understand the
      destructive effects of RBSDV infection on maize growth, comparative proteomic
      analyses of maize seedlings under RBSDV infection was performed using an
      integrated approach involving LC-MS/MS and Tandem Mass Tag (TMT) labeling.
      RESULTS: In total, 7615 maize proteins, 6319 of which were quantified. A total of
      116 differentially accumulated proteins (DAPs) were identified, including 35 up-
      and 81 down-regulated proteins under the RBSDV infection. Enrichment analysis
      showed that the DAPs were most strongly associated with cyanoamino acid
      metabolism, protein processing in ER, and ribosome-related pathways. Two sulfur
      metabolism-related proteins were significantly reduced, indicating that sulfur
      may participate in the resistance against RBSDV infection. Furthermore, 15 DAPs
      involved in six metabolic pathways were identified in maize under the RBSDV
      infection. CONCLUSIONS: Our data revealed that the responses of maize to RBSDV
      infection were controlled by various metabolic pathways.

PMID- 30208845
TI  - Hemophagocytic lymphohistiocytosis and congenital factor VII deficiency: a case
      report.
AB  - BACKGROUND: Hemophagocytic lymfohistiocytosis (HLH) is a rare, life-threatening
      hyperinflammation, characterized by immune system over-activation resulting in
      hemophagocytosis. HLH could appear as a primary disease caused by mutations of
      immune-regulatory genes, or develop as a result of viral or bacterial infections,
      or malignancy. Congenital factor VII (FVII) deficiency is a rare autosomal
      recessive disorder characterized by prolonged prothrombin time (PT) and low FVII,
      which may increase bleeding risk. CASE PRESENTATION: A 50-year-old woman was
      admitted for a fever persisted for 20 days, presenting with cytopenia, high
      hyperferritinemia, low activity of NK cells. Bone marrow aspiration showed
      hemophagocytosis. CT scanning found pulmonary infection. EBV and CMV were not
      detected. Genetic scanning did not find pathogenic mutation of a HLH NGS panel
      including 26 genes. This patient was treated as recommended by the HLH 2004
      Guidelines. Coagulation tests identified FVII deficiency. Genetic analysis of F7
      gene in the patient and her family members identified recurrent compound
      heterozygous F7 c.64 + 5G > A and c.1224 T > G (p.His408Gln) mutations in this
      patient and her brother who showed postoperative hemorrhage after surgical
      resection of renal cell carcinoma. Heterozygotes in this family were
      asymptomatic. CONCLUSIONS: To our knowledge, this is the first report of HLH in
      combination with congenital FVII deficiency in Chinese population.

PMID- 30208847
TI  - Association of different iron deficiency cutoffs with adverse outcomes in chronic
      kidney disease.
AB  - BACKGROUND: Iron deficiency is highly prevalent in chronic kidney disease (CKD)
      patients. In clinical practice, iron deficiency is defined based on a combination
      of two commonly used markers, ferritin and transferrin saturation (TSAT).
      However, no consensus has been reached which cutoffs of these parameters should
      be applied to define iron deficiency. Hence, we aimed to assess prospectively
      which cutoffs of ferritin and TSAT performed optimally for outcomes in CKD
      patients. METHODS: We meticulously analyzed 975 CKD community dwelling patients
      of the Prevention of Renal and Vascular Endstage Disease prospective study based
      on an estimated glomerular filtration rate < 60 ml/min/1.73m2, albuminuria > 30
      mg/24 h, or albumin-to-creatinine ratio >= 30 mg/g. Cox proportional hazard
      regression analyses using different sets and combinations of cutoffs of ferritin
      and TSAT were performed to assess prospective associations with all-cause
      mortality, cardiovascular mortality, and development of anemia. RESULTS: Of the
      included 975 CKD patients (62 +/- 12 years, 64% male with an estimated glomerular
      filtration rate of 77 +/- 23 ml/min/1.73m2), 173 CKD patients died during a
      median follow-up of 8.0 (interquartile range 7.5-8.7) years of which 70 from a
      cardiovascular cause. Furthermore, 164 CKD patients developed anemia. The highest
      risk for all-cause mortality (hazard ratio, 2.83; 95% confidence interval, 1.53
      5.24), cardiovascular mortality (4.15; 1.78-9.66), and developing anemia (3.07;
      1.69-5.57) was uniformly observed for a TSAT< 10%, independent of serum ferritin
      level. CONCLUSION: In this study, we have shown that of the traditionally used
      markers of iron status, reduced TSAT, especially TSAT< 10%, is most strongly
      associated with the risk of adverse outcomes in CKD patients irrespective of
      serum ferritin level, suggesting that clinicians should focus more on TSAT rather
      than ferritin in this patient setting. Specific attention to iron levels below
      this cutoff seems warranted in CKD patients.

PMID- 30208846
TI  - Genomic, expressional, protein-protein interactional analysis of Trihelix
      transcription factor genes in Setaria italia and inference of their evolutionary
      trajectory.
AB  - BACKGROUND: Trihelix transcription factors (TTF) play important roles in plant
      growth and response to adversity stress. Until now, genome-wide identification
      and analysis of this gene family in foxtail millet has not been available. Here,
      we identified TTF genes in the foxtail millet and its grass relatives, and
      characterized their functional domains. RESULTS: As to sequence divergence, TTF
      genes were previously divided into five subfamilies, I-V. We found that Trihelix
      family members in foxtail millet and other grasses mostly preserved their
      ancestral chromosomal locations during millions of years' evolution. Six amino
      acid sites of the SIP1 subfamily possibly were likely subjected to significant
      positive selection. Highest expression level was observed in the spica, with the
      SIP1 subfamily having highest expression level. As to the origination and
      expansion of the gene family, notably we showed that a subgroup of subfamily IV
      was the oldest, and therefore was separated to define a new subfamily O.
      Overtime, starting from the subfamily O, certain genes evolved to form
      subfamilies III and I, and later from subfamily I to develop subfamilies II and
      V. The oldest gene, Si1g016284, has the most structural changes, and a high
      expression in different tissues. What's more interesting is that it may have
      bridge the interaction with different proteins. CONCLUSIONS: By performing
      phylogenetic analysis using non-plant species, notably we showed that a subgroup
      of subfamily IV was the oldest, and therefore was separated to define a new
      subfamily O. Starting from the subfamily O, certain genes evolved to form other
      subfamilies. Our work will contribute to understanding the structural and
      functional innovation of Trihelix transcription factor, and the evolutionary
      trajectory.

PMID- 30208848
TI  - Comparative analysis of circular RNAs between soybean cytoplasmic male-sterile
      line NJCMS1A and its maintainer NJCMS1B by high-throughput sequencing.
AB  - BACKGROUND: Cytoplasmic male sterility (CMS) is a natural phenomenon of pollen
      abortion caused by the interaction between cytoplasmic genes and nuclear genes.
      CMS is a simple and effective pollination control system, and plays an important
      role in crop heterosis utilization. Circular RNAs (circRNAs) are a vital type of
      non-coding RNAs, which play crucial roles in microRNAs (miRNAs) function and post
      transcription control. To explore the expression profile and possible functions
      of circRNAs in the soybean CMS line NJCMS1A and its maintainer NJCMS1B, high
      throughput deep sequencing coupled with RNase R enrichment strategy was
      conducted. RESULTS: CircRNA libraries were constructed from flower buds of
      NJCMS1A and its maintainer NJCMS1B with three biological replicates. A total of
      2867 circRNAs were identified, with 1009 circRNAs differentially expressed
      between NJCMS1A and NJCMS1B based on analysis of high-throughput sequencing. Of
      the 12 randomly selected circRNAs with different expression levels, 10 showed
      consistent expression patterns based on high-throughput sequencing and
      quantitative real-time PCR analyses. Tissue specific expression patterns were
      also verified with two circRNAs by quantitative real-time PCR. Most parental
      genes of differentially expressed circRNAs were mainly involved in biological
      processes such as metabolic process, biological regulation, and reproductive
      process. Moreover, 83 miRNAs were predicted from the differentially expressed
      circRNAs, some of which were strongly related to pollen development and male
      fertility; The functions of miRNA targets were analyzed using Gene Ontology (GO)
      and Kyoto Encyclopedia of Genes and Genomes (KEGG), and the target mRNAs were
      significantly enriched in signal transduction and programmed cell death.
      Furthermore, a total of 165 soybean circRNAs were predicted to contain at least
      one internal ribosome entry site (IRES) element and an open reading frame,
      indicating their potential to encode polypeptides or proteins. CONCLUSIONS: Our
      study indicated that the circRNAs might participate in the regulation of flower
      and pollen development, which could provide a new insight into the molecular
      mechanisms of CMS in soybean.

PMID- 30208850
TI  - Evaluation of the CPR video decision aid with patients with end stage renal
      disease.
AB  - BACKGROUND: People with end stage renal disease (ESRD) face important health
      related decisions concerning end-of-life care and the use of life-support
      technologies. While people often want to be involved in making decisions about
      their health, there are many challenges. People with advanced illness may have
      limited or wavering ability to participate fully in decision-making conversations
      - or lack decisional capacity for making decisions. Additionally, they may have a
      limited understanding of CPR and tend to receive inconsistent information on the
      process and outcome of CPR. Unfortunately, these discussions are often avoided.
      Shared decision-making approaches are an approach to overcoming these challenges.
      The objectives of this research was to design, test, and analyze a novel CPR
      video decision aid (VDA) with nephrology patients and their families in a
      clinical setting. METHODS: The Interprofessional Shared Decision-making Model was
      used as a framework to guide the research. A prospective quasi-experimental
      design included pre/posttest measures of knowledge and confidence in decision
      making, and posttest only measure of uncertainty about the decision. RESULTS:
      Participant knowledge about CPR increased from a mean score of 4.8/9 (standard
      deviation [SD] = 1.65) before viewing the video to 7.5/9 (SD = 1.40) (p = 0.000)
      after viewing the video. Decisional self-efficacy improved slightly from 84% pre
      intervention (SD 17.04, range 20-100) to 86% after the intervention (SD 14.13,
      range 39-100) (p = 0.005) for patient participants. Before the intervention, most
      patients (43/49; 86%) had an order to have CPR in the physician orders and very
      few (7/49; 14%) had an order not to have CPR. Immediately after viewing the CPR
      VDA and completing the values clarification worksheet, fewer 28/49 (57%) chose to
      have CPR, 13 (27%) chose not to have CPR and 8 (16%) were unsure. CONCLUSIONS:
      The CPR-VDA was feasible and acceptable to patients with ESRD, their families and
      the healthcare team. The CPR-VDA positively affected decision-making: improving
      patient and family knowledge about CPR, clarity of values, patients' decisional
      self-efficacy, the congruence between documented physician's orders and patient
      choice, quality of communication about CPR, while reducing decisional conflict
      (uncertainty) amongst patients, families, and physicians.

PMID- 30208851
TI  - Why are hospitalisations too long? A simple checklist for identifying the main
      social barriers to hospital discharge from a nephrology ward.
AB  - The present increase in life span has been accompanied by an even higher increase
      in the burden of comorbidity. The challenges to healthcare systems are enormous
      and performance measures have been introduced to make the provision of healthcare
      more cost-efficient. Performance of hospitalisation is basically defined by the
      relationship between hospital stay, use of hospital resources, and main
      diagnosis/diagnoses and complication(s), adjusted for case mix. These factors,
      combined in different indexes, are compared with the performance of similar
      hospitals in the same and other countries. The reasons why an approach like this
      is being employed are clear.Cutting costs cannot be the only criteria, in
      particular in elderly, high-comorbidity patients: in this population, although
      social issues are important determinants of hospital stay, they are rarely taken
      into account or quantified in evaluations. Quantifying the impact of the "social
      barriers" to care can serve as a marker of the overall quality of treatment a
      network provides, and point to specific out-of-hospital needs, necessary to
      improve in-hospital performance. We therefore propose a simple, empiric medico
      social checklist that can be used in nephrology wards to assess the presence of
      social barriers to hospital discharge and quantify their weight.Using the
      checklist should allow: identifying patients with social frailty that could
      complicate hospitalisation and/or discharge; evaluating the social needs of
      patient and entourage at the beginning of hospitalisation, adopting timely
      procedures, within the partnership with out-of-hospital teams; facilitating
      prioritization of interventions by social workers.The following ten items were
      empirically identified: reason for hospitalisation; hospitalisation in relation
      to the caregiver's problems; recurrent unplanned hospitalisations or early re
      hospitalisation; social/family isolation; presence of a dependent relative in the
      patient's household; lack of housing or unsuitable housing/accommodation; loss of
      autonomy; lack of economic resources; lack of a safe environment; evidence of
      physical or psychological abuse.The simple tool here described needs validation;
      the present proposal is aimed at raising attention on the importance of non
      medical issues in medical organisation in our specialty, and is open to
      discussion, to allow its refinement.

PMID- 30208849
TI  - Searching for 3D structural models from a library of biological shapes using a
      few 2D experimental images.
AB  - BACKGROUND: Advancements in biophysical experimental techniques have pushed the
      limits in terms of the types of phenomena that can be characterized, the amount
      of data that can be produced and the resolution at which we can visualize them.
      Single particle techniques such as Electron Microscopy (EM) and X-ray free
      electron laser (XFEL) scattering require a large number of 2D images collected to
      resolve three-dimensional (3D) structures. In this study, we propose a quick
      strategy to retrieve potential 3D shapes, as low-resolution models, from a few 2D
      experimental images by searching a library of 2D projection images generated from
      existing 3D structures. RESULTS: We developed the protocol to assemble a non
      redundant set of 3D shapes for generating the 2D image library, and to retrieve
      potential match 3D shapes for query images, using EM data as a test. In our
      strategy, we disregard differences in volume size, giving previously unknown
      structures and conformations a greater number of 3D biological shapes as possible
      matches. We tested the strategy using images from three EM models as query images
      for searches against a library of 22750 2D projection images generated from 250
      random EM models. We found that our ability to identify 3D shapes that match the
      query images depends on how complex the outline of the 2D shapes are and whether
      they are represented in the search image library. CONCLUSIONS: Through our
      computational method, we are able to quickly retrieve a 3D shape from a few 2D
      projection images. Our approach has the potential for exploring other types of 2D
      single particle structural data such as from XFEL scattering experiments, for
      providing a tool to interpret low-resolution data that may be insufficient for 3D
      reconstruction, and for estimating the mixing of states or conformations that
      could exist in such experimental data.

PMID- 30208852
TI  - The alternative sigma factor RpoQ regulates colony morphology, biofilm formation
      and motility in the fish pathogen Aliivibrio salmonicida.
AB  - BACKGROUND: Quorum sensing (QS) is a cell-to cell communication system that
      bacteria use to synchronize activities as a group. LitR, the master regulator of
      QS in Aliivibrio salmonicida, was recently shown to regulate activities such as
      motility, rugosity and biofilm formation in a temperature dependent manner. LitR
      was also found to be a positive regulator of rpoQ. RpoQ is an alternative sigma
      factor belonging to the sigma -70 family. Alternative sigma factors direct gene
      transcription in response to environmental signals. In this work we have studied
      the role of RpoQ in biofilm formation, colony morphology and motility of A.
      salmonicida LFI1238. RESULTS: The rpoQ gene in A. salmonicida LFI1238 was deleted
      using allelic exchange. We found that RpoQ is a strong repressor of rugose colony
      morphology and biofilm formation, and that it controls motility of the bacteria.
      We also show that overexpression of rpoQ in a DeltalitR mutant of A. salmonicida
      disrupts the biofilm produced by the DeltalitR mutant and decreases its motility,
      whereas rpoQ overexpression in the wild-type completely eliminates the motility.
      CONCLUSION: The present work demonstrates that the RpoQ sigma factor is a novel
      regulatory component involved in modulating motility, colony morphology and
      biofilm formation in the fish pathogen A. salmonicida. The findings also confirm
      that RpoQ functions downstream of the QS master regulator LitR. However further
      studies are needed to elucidate how LitR and RpoQ work together in controlling
      phenotypes related to QS in A. salmonicida.

PMID- 30208853
TI  - Low pH-responsive proteins revealed by a 2-DE based MS approach and related
      physiological responses in Citrus leaves.
AB  - BACKGROUND: Rare data are available on the molecular responses of higher plants
      to low pH. Seedlings of 'Sour pummelo' (Citrus grandis) and 'Xuegan' (Citrus
      sinensis) were treated daily with nutrient solution at a pH of 2.5, 3, or 6
      (control) for nine months. Thereafter, we first used 2-dimensional
      electrophoresis (2-DE) to investigate low pH-responsive proteins in Citrus
      leaves. Meanwhile, we examined low pH-effects on leaf gas exchange,
      carbohydrates, ascorbate, dehydroascorbate and malondialdehyde. The objectives
      were to understand the adaptive mechanisms of Citrus to low pH and to identify
      the possible candidate proteins for low pH-tolerance. RESULTS: Our results
      demonstrated that Citrus were tolerant to low pH, with a slightly higher low pH
      tolerance in the C. sinensis than in the C. grandis. Using 2-DE, we identified
      more pH 2.5-responsive proteins than pH 3-responsive proteins in leaves. This
      paper discussed mainly on the pH 2.5-responsive proteins. pH 2.5 decreased the
      abundances of proteins involved in ribulose bisphosphate carboxylase/oxygenase
      activation, Calvin cycle, carbon fixation, chlorophyll biosynthesis and electron
      transport, hence lowering chlorophyll level, electron transport rate and
      photosynthesis. The higher oxidative damage in the pH 2.5-treated C. grandis
      leaves might be due to a combination of factors including higher production of
      reactive oxygen species, more proteins decreased in abundance involved in
      antioxidation and detoxification, and lower ascorbate level. Protein and amino
      acid metabolisms were less affected in the C. sinensis leaves than those in the
      C. grandis leaves when exposed to pH 2.5. The abundances of proteins related to
      jasmonic acid biosynthesis and signal transduction were increased and decreased
      in the pH 2.5-treated C. sinensis and C. grandis leaves, respectively.
      CONCLUSIONS: This is the first report on low pH-responsive proteins in higher
      plants. Thus, our results provide some novel information on low pH-toxicity and 
      tolerance in higher plants.

PMID- 30208855
TI  - Priority-Lasso: a simple hierarchical approach to the prediction of clinical
      outcome using multi-omics data.
AB  - BACKGROUND: The inclusion of high-dimensional omics data in prediction models has
      become a well-studied topic in the last decades. Although most of these methods
      do not account for possibly different types of variables in the set of covariates
      available in the same dataset, there are many such scenarios where the variables
      can be structured in blocks of different types, e.g., clinical, transcriptomic,
      and methylation data. To date, there exist a few computationally intensive
      approaches that make use of block structures of this kind. RESULTS: In this paper
      we present priority-Lasso, an intuitive and practical analysis strategy for
      building prediction models based on Lasso that takes such block structures into
      account. It requires the definition of a priority order of blocks of data. Lasso
      models are calculated successively for every block and the fitted values of every
      step are included as an offset in the fit of the next step. We apply priority
      Lasso in different settings on an acute myeloid leukemia (AML) dataset consisting
      of clinical variables, cytogenetics, gene mutations and expression variables, and
      compare its performance on an independent validation dataset to the performance
      of standard Lasso models. CONCLUSION: The results show that priority-Lasso is
      able to keep pace with Lasso in terms of prediction accuracy. Variables of blocks
      with higher priorities are favored over variables of blocks with lower priority,
      which results in easily usable and transportable models for clinical practice.

PMID- 30208854
TI  - Physical activity promotion for patients transitioning to dialysis using the
      "Exercise is Medicine" framework: a multi-center randomized pragmatic trial (EIM
      CKD trial) protocol.
AB  - BACKGROUND: Patients on dialysis are physically inactive, with most reporting
      activity levels below the fifth percentile of healthy age-matched groups. Several
      small studies have reported efficacy of diverse exercise interventions among
      persons with CKD and those on dialysis. However, no single intervention has been
      widely adopted in real-world practice, despite a clear need in this vulnerable
      population with high rates of mortality, frailty, and skilled nursing
      hospitalizations. METHODS/DESIGN: We describe a pragmatic clinical trial for an
      exercise intervention among patients transitioning to dialysis. We will use an
      existing framework - Exercise is Medicine (EIM) - developed by the American
      College of Sports Medicine. After undertaking formative qualitative research to
      tailor the EIM framework to the advanced CKD population (eGFR < 30
      ml/min/1.73m2), we will randomize 96 patients from two regions-Atlanta and Bay
      Area-in two intervention arms with incremental levels of clinical-community
      integration: physical activity assessment during Nephrology clinical visit, brief
      counseling at pre-dialysis education, and physical activity wearable (group 1)
      versus group 1 intervention components plus a referral to a free, EIM
      practitioner-led group exercise program over 16 weeks (group 2; 8 week core
      intervention; 8-week follow up). We will assess efficacy by comparing between
      group differences in minutes/week of objectively measured moderate intensity
      physical activity. To evaluate implementation, we will use questionnaires for
      assessing barriers to referral, participation and retention along the path of the
      intervention. Further we will have a plan for dissemination of the intervention
      by partnering with relevant stakeholders. DISCUSSION: The overall goal is to
      inform the development of a practical, cost-conscious intervention "package" that
      addresses barriers and challenges to physical activity commonly faced by patients
      with advanced CKD and can be disseminated amongst interested practices. TRIAL
      REGISTRATION: ClinicalTrials.gov identifier (Dated:10/17/2017): NCT03311763 .

PMID- 30208856
TI  - Crescentic glomerulonephritis with anti-GBM antibody but no glomerular
      deposition.
AB  - BACKGROUND: Anti-glomerular basement membrane (GBM) antibodies are highly
      specific for Goodpasture's or anti-GBM disease, in which they are generally
      directed against the non-collagenous (NC1) domain of the alpha 3 chain of type IV
      collagen(alpha3(IV)), and less commonly, toward the alpha 4(IV) or alpha 5(IV)
      chains, which form a triple helical structure in GBM and alveolar basement
      membrane (ABM). Alterations in the hexameric structure of the NC1 (alpha3 (IV)),
      allows novel epitopes to be exposed and an immune response to develop, with
      subsequent linear antibody deposition along the GBM, leading to a crescentic
      glomerulonephritis. Positive anti-GBM antibodies are assumed to be pathogenic and
      capable of binding GBM in vivo, especially in the context of rapidly progressive
      glomerulonephritis. We have investigated patients with circulating anti-GBM
      antibodies, reactive to alpha3 (IV) and human GBM by immunoassays and Western
      blotting respectively, with focal necrotising crescentic glomerulonephritis but
      no linear GBM antibody deposition on immunohistochemistry. Three out of four were
      also ANCA positive. Despite not binding native GBM, patients' sera showed linear
      binding to primate glomeruli by indirect immunofluorescence, in the 2 cases
      tested. Following treatment, significant improvements in kidney function were
      found in 3/4 patients. CASE PRESENTATION: We present four patients with
      crescentic glomerulonephritis and circulating anti-GBM antibodies, but no
      glomerular binding. CONCLUSIONS: These novel findings, demonstrate that in some
      patients anti-GBM antibodies may not bind their own GBM. This has important
      implications for clinical diagnosis, suggesting that histological confirmation of
      kidney injury by anti-GBM antibodies should be obtained, as non-binding GBM
      antibodies may be associated with significant renal recovery.

PMID- 30208858
TI  - Estimation of an inter-rater intra-class correlation coefficient that overcomes
      common assumption violations in the assessment of health measurement scales.
AB  - BACKGROUND: Intraclass correlation coefficients (ICC) are recommended for the
      assessment of the reliability of measurement scales. However, the ICC is subject
      to a variety of statistical assumptions such as normality and stable variance,
      which are rarely considered in health applications. METHODS: A Bayesian approach
      using hierarchical regression and variance-function modeling is proposed to
      estimate the ICC with emphasis on accounting for heterogeneous variances across a
      measurement scale. As an application, we review the implementation of using an
      ICC to evaluate the reliability of Observer OPTION5, an instrument which used
      trained raters to evaluate the level of Shared Decision Making between clinicians
      and patients. The study used two raters to evaluate recordings of 311 clinical
      encounters across three studies to evaluate the impact of using a Personal
      Decision Aid over usual care. We particularly focus on deriving an estimate for
      the ICC when multiple studies are being considered as part of the data. RESULTS:
      The results demonstrate that ICC varies substantially across studies and patient
      physician encounters within studies. Using the new framework we developed, the
      study-specific ICCs were estimated to be 0.821, 0.295, and 0.644. If the within-
      and between-encounter variances were assumed to be the same across studies, the
      estimated within-study ICC was 0.609. If heteroscedasticity is not properly
      adjusted for, the within-study ICC estimate was inflated to be as high as 0.640.
      Finally, if the data were pooled across studies without accounting for the
      variability between studies then ICC estimates were further inflated by
      approximately 0.02 while formerly allowing for between study variation in the ICC
      inflated its estimated value by approximately 0.066 to 0.072 depending on the
      model. CONCLUSION: We demonstrated that misuse of the ICC statistics under common
      assumption violations leads to misleading and likely inflated estimates of
      interrater reliability. A statistical analysis that overcomes these violations by
      expanding the standard statistical model to account for them leads to estimates
      that are a better reflection of a measurement scale's reliability while
      maintaining ease of interpretation. Bayesian methods are particularly well suited
      to estimating the expanded statistical model.

PMID- 30208857
TI  - Effects of whole-body electromyostimulation combined with individualized
      nutritional support on body composition in patients with advanced cancer: a
      controlled pilot trial.
AB  - BACKGROUND: Physical exercise and nutritional treatment are promising measures to
      prevent muscle wasting that is frequently observed in advanced-stage cancer
      patients. However, conventional exercise is not always suitable for these
      patients due to physical weakness and therapeutic side effects. In this pilot
      study, we examined the effect of a combined approach of the novel training method
      whole-body electromyostimulation (WB-EMS) and individualized nutritional support
      on body composition with primary focus on skeletal muscle mass in advanced cancer
      patients under oncological treatment. METHODS: In a non-randomized controlled
      trial design patients (56.5% male; 59.9 +/- 12.7 years) with advanced solid
      tumors (UICC III/IV, N = 131) undergoing anti-cancer therapy were allocated to a
      usual care control group (n = 35) receiving individualized nutritional support or
      to an intervention group (n = 96) that additionally performed a supervised
      physical exercise program in form of 20 min WB-EMS sessions (bipolar, 85 Hz)
      2*/week for 12 weeks. The primary outcome of skeletal muscle mass and secondary
      outcomes of body composition, body weight and hand grip strength were measured at
      baseline, in weeks 4, 8 and 12 by bioelectrical impedance analysis and hand
      dynamometer. Effects of WB-EMS were estimated by linear mixed models. Secondary
      outcomes of physical function, hematological and blood chemistry parameters,
      quality of life and fatigue were assessed at baseline and week 12. Changes were
      analyzed by t-tests, Wilcoxon signed-rank or Mann-Whitney-U-tests. RESULTS:
      Twenty-four patients of the control and 58 of the WB-EMS group completed the 12
      week trial. Patients of the WB-EMS group had a significantly higher skeletal
      muscle mass (0.53 kg [0.08, 0.98]; p = 0.022) and body weight (1.02 kg [0.05,
      1.98]; p = 0.039) compared to controls at the end of intervention. WB-EMS also
      significantly improved physical function and performance status (p < 0.05). No
      significant differences of changes in quality of life, fatigue and blood
      parameters were detected between the study groups after 12 weeks. CONCLUSIONS:
      Supervised WB-EMS training is a safe strength training method and combined with
      nutritional support it shows promising effects against muscle wasting and on
      physical function in advanced-stage cancer patients undergoing treatment. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT02293239 (Date: November 18, 2014).

PMID- 30208859
TI  - Three cases of multicentric carpotarsal osteolysis syndrome: a case series.
AB  - BACKGROUND: Multicentric carpotarsal osteolysis syndrome (MCTO) is characterized
      by progressive destruction and disappearance of the carpal and tarsal bones
      associated with nephropathy. MCTO is caused by loss-of-function mutations in the
      MAF bZIP transcription factor B (MAFB) gene. CASE PRESENTATION: This report
      describes three unrelated patients with MAFB mutations, including two male and
      one female patient. Osteolytic lesions in the carpal and tarsal bones were
      detected at 2 years, 12 years, and 14 months of age, respectively. Associated
      proteinuria was noted at 4 years, 12 years, and 3 months of age, respectively.
      Kidney biopsy was performed in two of them and revealed focal segmental
      glomerulosclerosis (FSGS). One patient showed progression to end-stage renal
      disease, that is by 1 year after the detection of proteinuria. The second patient
      had persistent proteinuria but maintained normal renal function. In the third
      patient, who did not undergo a kidney biopsy, the proteinuria disappeared
      spontaneously. The bony lesions worsened progressively in all three patients.
      Mutational study of MAFB revealed three different mutations, two novel mutations
      [c.183C > A (p.Ser61Arg) and c.211C > G (p.Pro71Ala)] and one known mutation
      [c.212C > T (p.Pro71Leu)]. CONCLUSION: We report three cases with MCTO and two
      novel MAFB mutations. The renal phenotypes were different among the three
      patients, whereas progressive worsening of the bony lesions was common in all
      patients. We also confirmed FSGS to be an early renal pathologic finding in two
      cases. A diagnosis of MCTO should be considered in patients with progressive bone
      loss concentrated primarily in the carpal and tarsal bones and kidney
      involvement, such as proteinuria.

PMID- 30208860
TI  - Predictors of breastfeeding duration in a predominantly Maori population in New
      Zealand.
AB  - BACKGROUND: Although breastfeeding duration in New Zealand's indigenous Maori is
      shorter than in non-Maori, we know little about barriers or motivators of
      breastfeeding in this community. The aim of this analysis was to identify
      predictors for extended duration of breastfeeding amongst participants drawn from
      predominantly Maori communities in regional Hawke's Bay. METHODS: Mother/baby
      dyads were recruited from two midwifery practices serving predominantly Maori
      women in mostly deprived areas, for a randomised controlled trial comparing the
      risks and benefits of an indigenous sleeping device (wahakura) and a bassinet.
      Questionnaires were administered at baseline (pregnancy) and at one, three and
      six months postnatal. Several questions relating to breastfeeding and factors
      associated with breastfeeding were included. The data from both groups were
      pooled to examine predictors of breastfeeding duration. RESULTS: Maori comprised
      70.5% of the 197 participants recruited. The median time infants were fully
      breastfed was eight weeks and Maori women were more likely to breastfeed for a
      shorter duration than New Zealand European women with an odds-ratio (OR) of 0.45
      (95% CI 0.24, 0.85). The key predictors for extended duration of breastfeeding
      were the strong support of the mother's partner (OR = 3.64, 95% CI 1.76, 7.55) or
      her mother for breastfeeding (OR = 2.47, 95% CI 1.27, 4.82), longer intended
      duration of maternal breastfeeding (OR = 1.02, 95% CI 1.00, 1.03) and being an
      older mother (OR = 1.07, 95% CI 1.02, 1.12). The key predictors for shorter
      duration of breastfeeding were pacifier use (OR = 0.28, 95% CI 0.17, 0.46), daily
      cigarette smoking (OR = 0.51, 95% CI 0.37, 0.69), alcohol use (OR = 0.54, 95% CI
      0.31, 0.93) and living in a more deprived area (OR 0.40, 95% CI 0.22, 0.72).
      CONCLUSIONS: Breastfeeding duration in this group of mainly Maori women was
      shorter than the national average. Increasing the duration of breastfeeding by
      these mothers could be further facilitated by ante and postnatal education
      involving their own mothers and their partners in the support of breastfeeding
      and by addressing pacifier use, smoking and alcohol use.

PMID- 30208861
TI  - A systematic review of cardiac time intervals utilising non-invasive fetal
      electrocardiogram in normal fetuses.
AB  - BACKGROUND: Non-invasive fetal electrocardiogram (NIFECG) is an evolving
      technology in fetal surveillance which is attracting increasing research
      interest. There is however, only limited data outlining the reference ranges for
      normal cardiac time intervals (CTIs). The objective of our group was to carry out
      a systematic review to outline normal fetal CTIs using NIFECG. METHODS: A
      systematic review of peer reviewed literature was performed, searching
      PUBMED,Ovid MEDLINE and EMBASE. The outcomes of interest included fetal CTIs (P
      wave duration, PR interval, QRS duration and QT interval) and a descriptive
      summary of relevant studies as well. The outcomes were grouped as early pre-term
      (<= 32 weeks), moderate to late pre-term (32-37 weeks) and term (37-41 weeks).
      RESULTS: 8 studies were identified as suitable for inclusion. Reference ranges of
      CTIs were generated. Both PR interval and QRS duration demonstrated a linear
      correlation with advancing gestation. Several studies also demonstrated a
      reduction in signal acquisition between 27 and 32 weeks due to the attenuation by
      vernix caseosa. In this group, both the P wave and T waves were difficult to
      detect due to signal strength and interference. CONCLUSION: NIFECG demonstrates
      utility to quantify CTIs in the fetus, particularly at advanced gestations.
      Larger prospective studies should be directed towards establishing reliable CTIs
      across various gestations.

PMID- 30208862
TI  - Pattern dystrophies in patients treated with deferoxamine: report of two cases
      and review of the literature.
AB  - BACKGROUND: Deferoxamine (DFO) is one of the most commonly used chelation
      treatments for transfusional hemosiderosis. Pattern dystrophies constitute a
      distinct entity of retinal disorders that has been occasionally identified in
      association with deferoxamine. CASE PRESENTATION: We report two cases of
      bilateral macular pattern dystrophy in transfusion dependent patients undergoing
      chronic chelation therapy with deferoxamine due to thalassemias. Our patients
      were evaluated with multimodal imaging and the results are presented. Both
      patients had normal cone and rod responses in the full-field electroretinogram
      and continued the prescribed chelation therapy, after hematology consult. The
      patients were followed up every 3 months for 2 and 4 years respectively for
      possible deterioration. Their best corrected visual acuity remained stable with
      no anatomic change on Optical Coherence Tomography findings. CONCLUSION:
      Multimodal imaging of our patients allowed a better evaluation and possibly
      earlier detection of the DFO-related changes. Screening and close follow up of
      patients under chronic chelating therapy is important in order to promptly
      diagnose and manage possible toxicity either with discontinuation of the
      offending agent or dose modification.

PMID- 30208863
TI  - Clinical benefit and radiological response with BRAF inhibitor in a patient with
      recurrent ameloblastoma harboring V600E mutation.
AB  - BACKGROUND: Ameloblastoma is a slow-growing neoplasm of the jaw, for which the
      standard treatment is surgical removal of the lesion with high recurrence rates
      and elevated morbidity. Systemic therapy is not established in the literature.
      CASE PRESENTATION: We present a case of a 29-year-old woman diagnosed with an
      ameloblastoma of the left mandible who had been subjected to several surgical
      procedures over twenty years due to multiple local recurrences. Molecular testing
      revealed a BRAF V600E mutation, and vemurafenib was started. She experienced
      complete resolution of symptoms related to the disease, and image scans evidenced
      continuous shrinkage of the neoplastic lesion after eleven months of therapy.
      CONCLUSION: This is the first report showing clinical benefit and radiological
      response with vemrafenib for recurrent ameloblastoma. Targeted therapy addressing
      BRAF V600E mutation has the potential to change clinical practice of this rare
      disease.

PMID- 30208864
TI  - Risk factors for multidrug-resistant tuberculosis among tuberculosis patients in
      Serbia: a case-control study.
AB  - BACKGROUND: Multidrug resistant (MDR) tuberculosis (TB) represents TB which is
      simultaneous resistant to at least rifampicin (R) and isoniazid (H). Identifying
      inadequate therapy as the main cause of this form of the disease and explaining
      the factors leading to its occurrence, numerous social determinants that affect
      the risk of developing resistance are highlighted. The objectives of the study
      was to identify independent factors of MDR-TB among tuberculosis patients.
      METHODS: Case-control study was conducted from 1st September 2009 to 1st June
      2014 in 31 healthcare institutions in Serbia where MDR-TB and TB patients were
      treated. TB patients infected with MDR- M. tuberculosis and non MDR- M.
      tuberculosis strain were considered as cases and controls, respectively. Cases
      and controls were matched by the date of hospitalization. The data was collected
      using structured questionnaire with face to face interview. Bivariate and
      multivariable logistic regression analysis (MLRA) were used to identify
      determinants associated with MDR-TB. RESULTS: A total of 124 respondents, 31
      cases and 93 controls were participated in the study. MLRA identified six
      significant independent risk factors for the occurrence of MDR-TB as follows:
      monthly income of the family (Odds ratio (OR) = 3.71; 95% Confidence Interval
      (CI) = 1.22-11.28), defaulting from treatment (OR = 3.33; 95% CI = 1.14-9.09),
      stigma associated with TB (OR = 2.97; 95% CI = 1.18-7.45), subjective feeling of
      sadness (OR = 4.05; 95% CI = 1.69-9.70), use of sedatives (OR = 2.79; 95% CI =
      1.02-7.65) and chronic obstructive pulmonary disease (OR = 4.51; 95% CI = 1.07
      18.96). CONCLUSION: In order to reduce burden of drug resistance, strategies of
      controlling MDR-TB in Serbia should emphasize multi-sectorial actions, addressing
      health care and social needs of TB patients.

PMID- 30208865
TI  - Effect of mildly elevated thyroid-stimulating hormone during the first trimester
      on adverse pregnancy outcomes.
AB  - BACKGROUND: To investigate the effect of a mildly elevated thyroid-stimulating
      hormone (TSH) concentration between 2.5 and 4.0 mIU/L during the first trimester
      on pregnancy outcomes in thyroid peroxydase antibody (TPOAb)-negative pregnant
      women. METHODS: A total of 1858 pregnant women who were TPOAb-negative before 13+
      6 gestational weeks, received regular prenatal services, and delivered in the
      third affiliated hospital of Sun Yat-Sen University were recruited from June 2016
      to June 2017. Measurements of thyroid function (TSH, free T4 [FT4] and TPOAb) and
      adverse pregnancy outcomes were assessed and recorded. RESULTS: Among the 1858
      study participants, the 97.5th percentile for TSH was 3.76 mIU/L, and 142 women
      (7.6%) had mildly elevated TSH levels between 2.5 and 4.0 mIU/L. No differences
      in the incidence of adverse pregnancy outcomes were observed between patients
      with a mildly elevated TSH level and those with a normal TSH level (< 2.5 mIU/L).
      CONCLUSION: A mildly elevated TSH concentration (2.5-4.0 mIU/L) during the first
      trimester of pregnancy in TPOAb-negative women was not associated with adverse
      pregnancy outcomes in our study population. Accordingly, it may be possible to
      raise the upper limit of the healthy TSH reference range for pregnant women.

PMID- 30208867
TI  - Genomic profiles of primary and metastatic esophageal adenocarcinoma identified
      via digital sorting of pure cell populations: results from a case report.
AB  - BACKGROUND: We report on a female patient who underwent primary radical resection
      for a stage 2B Her-2-positive Barrett's-type esophageal adenocarcinoma (EAC).
      Despite Her-2 targeted therapy, her disease recurred and required repeated
      metastectomies. CASE PRESENTATION: Digital cell sorting and targeted sequencing
      of cancer sub-clones from EAC and metastases revealed a completely mutated TP53,
      whereas the sorted stromal cells were wild-type. Her-2 amplification was
      significantly lower in the metastases when the patient became therapy-resistant.
      CONCLUSIONS: The mechanism of therapy resistance illustrated by this case could
      only be detected through accurate analysis of tumor sub-populations.
      Investigating tumor sub-populations of recurrent disease is important for
      adjusting therapy in recurrent EAC.

PMID- 30208866
TI  - 'DURVIT': a phase-I trial of single low-dose durvalumab (Medi4736)
      IntraTumourally injected in cervical cancer: safety, toxicity and effect on the
      primary tumour- and lymph node microenvironment.
AB  - BACKGROUND: Treatment with programmed cell death receptor (PD-1) and programmed
      cell death ligand 1 (PD-L1) inhibitors is a promising strategy to lift tumour
      induced immune response suppression. However, the current systemic treatment
      often causes autoimmune side effects. In more than 50% of squamous cell cervical
      cancer, PD-L1 expression is detected. Moreover, we observed high and interrelated
      rates of PD-L1 positive macrophages and regulatory T cells in metastatic lymph
      nodes of cervical cancer patients. As cervical cancer in general initially
      metastasizes to regional lymph nodes, local administration of durvalumab (a PD-L1
      checkpoint inhibitor) at an early stage will deliver these antibodies exactly
      where they are needed, facilitating immune protection. This may result in a
      clinical benefit while reducing undesirable side effects. METHODS: DURVIT is a
      non-randomized, single-arm, open-label, phase I study. Three escalating dose
      levels of intratumourally (i.t.) injected durvalumab will be tested, i.e. 5, 10
      and 20 mg (three patients per dose level, with an additional three at the highest
      tolerated dose). The primary endpoint of this phase-I study is safety. Immune
      monitoring will consist of flow cytometric, immunohistochemical and functional T
      cell reactivity testing. The first patient has been included in this trial in
      November 2017. DISCUSSION: Evidence of safety and biological efficacy of this
      locally administered checkpoint blockade may expand adjuvant therapy options for
      cervical cancer patients. Early metastatic spread of cervical cancer cells may
      thus be controlled in the draining lymph node basin, and beyond, and hopefully
      delay or even prevent the onset of disease recurrence. TRIAL REGISTRATION:
      NTR6119 , 1-nov-2016.

PMID- 30208869
TI  - Assessing quality of life using WHOQOL-BREF: a cross-sectional study on the
      association between quality of life and neighborhood environmental satisfaction,
      and the mediating effect of health-related behaviors.
AB  - BACKGROUND: Quality of life (QOL) is an important component in assessing people's
      health. Environmental quality can influence people's QOL in the physical health,
      psychological, social relationships and environment domains. QOL in the four
      domains, overall QOL and general heath of residents living in the Kowloon
      Peninsula of Hong Kong were assessed. The association between satisfaction with
      the neighborhood environment and QOL, and health-related behaviors which mediated
      the effect were investigated. METHODS: A sample of 317 residents completed a
      questionnaire which comprised the WHOQOL-BREF (Hong Kong version) to assess QOL,
      the International Physical Activity Questionnaire (IPAQ) to study physical
      activities, and questions on satisfaction with the neighborhood environment,
      health-related behaviors and socio-demographics. One-way ANOVA and linear
      regression were used to study the associations between environmental satisfaction
      and QOL in the four domains, overall QOL and general health, followed by
      assessing the relationships between environmental satisfaction and the potential
      health-related behavior mediators with regression tests. Mediation analysis was
      conducted using multiple linear regressions to study the effects of environmental
      satisfaction on QOL in the four domains, overall QOL and general health, as well
      as the potential mediating roles played by various health-related behaviors. A P
      value of < 0.05 was considered as statistically significant. RESULTS: The
      residents had a relatively higher physical health mean score of 70.83 +/- 12.69,
      and a lower environmental mean score of 61.98 +/- 13.76. Moderate satisfaction
      with the neighborhood environment had a significant relationship with QOL in the
      psychological domain (beta = 0.170, P = 0.006), however, this effect was
      partially mediated by the non-smoking behavior of the residents (beta = 0.143, P
      = 0.022). CONCLUSIONS: Our residents had lower QOL in the physical health and
      psychological domains but similar QOL in the social relationships and
      environmental domains compared to other countries. Only QOL in the psychological
      domain could be predicted by the satisfaction with the neighborhood environment,
      and non-smoking status was a partial mediator of the effect of moderate
      environmental satisfaction on QOL in the psychological domain. Refrain from
      smoking seems to be able to lower the influence of neighborhood environment on
      people's QOL in the psychological domain to a certain extent.

PMID- 30208868
TI  - What makes the pregnant women revisit public hospitals for research? Participant
      engagement and retention trial in a public hospital (PERTH): an RCT protocol.
AB  - BACKGROUND: Cohort studies have public health importance as they effectively
      provide evidence on determinants of health from a life course perspective.
      Researchers often confront the poor follow-up rates as a major challenge in the
      successful conduct of cohort studies. We are currently recruiting in a birth
      cohort study, titled as "Maternal Antecedents of Adiposity and Studying the
      Transgenerational role of Hyperglycemia and Insulin" (MAASTHI) in a public
      hospital; with the aim of assessing maternal glycemic levels on the risk of
      adverse fetal outcomes. Nested within the ongoing cohort, the proposed trial aims
      to evaluate the effectiveness of two interventions in improving the follow-up in
      the cohort study in a public hospital. METHODS: A randomized trial of 795
      pregnant women, with 265 women each in three arms observed through pregnancy,
      until their baby is 14 weeks old. The comparator group receives a standard
      leaflet, with details on the importance of glucose testing and regular follow up
      in pregnancy. Intervention arm-1 will receive the standard leaflet plus
      individualized messages, through an Interactive Voice Response (IVR) system; a
      type of computer-linked telephone intervention system to remind the participants
      about the lab test and follow-up dates. Intervention arm- 2 will have the
      opportunity to attend Mother and Baby Affairs (MBA) workshops, which will provide
      information on Gestational Diabetes Mellitus (GDM) screening and management to
      pregnant women and personalized counselling services. The outcome of interest is
      the difference in the proportion of participants completing follow-up at
      different points in time, among three arms. DISCUSSION: Between the two
      interventions (IVR and MBA), the study results would uncover the contextually
      specific, timely intervention, which can increase the proportion of pregnant
      women followed up in public hospitals. If effective, this study will provide
      information on an effective intervention, useful in ensuring the success of
      longitudinal follow-up in the public hospitals. TRIAL REGISTRATION: NCT03088501 ,
      Date Registered: 16/03/2017.

PMID- 30208870
TI  - Essential Care for Every Baby: improving compliance with newborn care practices
      in rural Nicaragua.
AB  - BACKGROUND: Neonatal mortality comprises an increasing proportion of childhood
      deaths in the developing world. Essential newborn care practices as recommended
      by the WHO may improve neonatal outcomes in resource limited settings. Our
      objective was to pilot a Helping Babies Breathe and Essential Care for Every Baby
      (HBB and ECEB) implementation package using HBB-ECEB training combined with
      supportive supervision in rural Nicaragua. METHODS: We employed an HBB-ECEB
      implementation package in El Ayote and Santo Domingo, two rural municipalities in
      Nicaragua and used a pre- and post- data collection design for comparison.
      Following a period of pre-intervention data collection (June-August 2015), care
      providers were trained in HBB and ECEB using a train-the- trainer model. An
      external supportive supervisor monitored processes of care and collected data.
      Data on newborn care processes and short-term outcomes such as hypothermia were
      collected from facility medical records and analyzed using standard run charts.
      Home visits were used to determine breastfeeding rates at 7, 30 and 60 days.
      RESULTS: There were 480 institutional births during the study period (June 2015
      June 2016). Following the HBB-ECEB implementation package, cord care improved
      (pre-intervention median 66%; post-intervention shift to >=85%) and early skin-to
      skin care improved (pre-intervention median 0%; post-intervention shift to >=56%,
      with a high of 92% in June 2016). Rates of administration of ophthalmic ointment
      and vitamin K were high pre-intervention (median 97%) and remained high. Early
      initiation of breastfeeding increased with a pre-intervention median of 25% and
      post-intervention shift to >=28%, with a peak of 81% in June 2016. Exclusive
      breastfeeding rates increased short-term but were not significantly different by
      60-days of life (9% pre-intervention versus 21% post-intervention). CONCLUSIONS:
      The implementation of the HBB-ECEB programs combined with supportive supervision
      improved the quality of care for newborns in terms of cord care, early skin-to
      skin care and early initiation of breastfeeding. The rates of administration of
      ophthalmic ointment and vitamin K were high pre- intervention and remained high
      afterwards. These findings show that HBB-ECEB programs implemented with
      supportive supervision can improve quality of care for newborns.

PMID- 30208871
TI  - Study protocol: HepaT1ca - an observational clinical cohort study to quantify
      liver health in surgical candidates for liver malignancies.
AB  - BACKGROUND: Accurate assessment of liver health prior to undertaking resectional
      liver surgery or chemoembolisation for primary and secondary cancers is essential
      for patient safety and optimal outcomes. LiverMultiScanTM, an MRI-based
      technology, non-invasively quantifies hepatic fibroinflammatory disease,
      steatosis and iron content. We hypothesise that LiverMultiScanTMcan quantify
      liver health prior to surgery and inform the risk assessment for patients
      considering liver surgery or chemoembolization and seek to evaluate this
      technology in an operational environment. METHODS/DESIGN: HepaT1ca is an
      observational cohort study in two tertiary-referral liver surgery centres in the
      United Kingdom. The primary outcome is correlation between the pre-operative
      liver health assessment score (Hepatica score - calculated by weighting future
      remnant liver volume by liver inflammation and fibrosis (LIF) score) and the post
      operative liver function composite integer-based risk (Hyder-Pawlik) score. With
      ethical approval and fully-informed consent, individuals considering liver
      surgery for primary or secondary cancer will undergo clinical assessment, blood
      sampling, and LiverMultiScanTMmultiparametric MRI before and after surgical liver
      resection or TACE. In nested cohorts of individuals undergoing chemotherapy prior
      to surgery, or those undergoing portal vein embolization (PVE) as an adjunct to
      surgery, an additional testing session prior to commencement of treatment will
      occur. Tissue will be examined histologically and by immunohistochemistry. Pre
      operative liver health assessment scores and the post-operative risk scores will
      be correlated to define the ability of LiverMultiScanTMto predict the risk of
      post-operative morbidity and mortality. Because technology performance in this
      setting is unknown, a pragmatic sample size will be used. For the primary
      outcome, n = 200 for the main cohort will allow detection of a minimum
      correlation coefficient of 0.2 with 5% significance and power of 80%. DISCUSSION:
      This study will refine the technology and clinical application of multiparametric
      MRI (including LiverMultiScanTM), to quantify pre-existing liver health and
      predict post-intervention outcomes following liver resection. If successful, this
      study will advance the technology and support the use of multiparametric MRI as
      part of an enhanced pre-operative assessment to improve patient safety and to
      personalise operative risk assessment of liver surgery/non-surgical intervention.
      TRIAL REGISTRATION: This study is registered on ClinicalTrials.gov Identifier:
      NCT03213314 .

PMID- 30208872
TI  - Perceived barriers and facilitators in providing palliative care for people with
      severe dementia: the healthcare professionals' experiences.
AB  - BACKGROUND: Dementia has become a major public health issue worldwide due to its
      rapidly increasing prevalence and an increasing number of dementia-related deaths
      in long-term care facilities. The aim of this study was to examine health
      professionals' experiences of potential barriers and facilitators in providing
      palliative care for people with severe dementia in long-term care facilities.
      METHODS: This was a qualitative descriptive study. The data were collected from
      four focus groups and 20 individual in-depth interviews with healthcare
      professionals from four Norwegian nursing homes. The data were analysed by
      thematic text analysis, as described by Braun and Clarke. RESULTS: The major
      findings indicate that healthcare professionals experience a lack of continuity
      as the main barrier to facilitating palliative care. Time pressure and increased
      efficiency requirements especially affect the weakest and bedridden residents
      with dementia. The healthcare professionals feel conflicted between wanting to
      spend more time caring for each individual resident and feeling pressure to help
      everyone. Although resources are scarce, dying residents are always given
      priority by healthcare professionals, either by the hiring of extra personnel or
      the reorganization of tasks in a way that facilitates someone staying with the
      terminal resident. Advanced care planning was highlighted as a facilitator in
      providing palliative care, but the extensive use of temporary staff among nurses
      and doctors and the relocation between the sheltered and long-term wards threaten
      the continuity in planning and providing palliative care. CONCLUSIONS: The
      findings indicate that healthcare professionals experienced several structural
      barriers that prevented the provision of palliative care to people with severe
      dementia in long-term care facilities. Increasing demands for economic
      rationality lead to a lack of continuity of care. Organizational changes, such as
      measures to increase the competence and the proportion of permanent employees and
      the prevention of burdensome end-of-life transitions, should be implemented to
      improve continuity and quality of care.

PMID- 30208874
TI  - A qualitative study to explore the attitudes of women and obstetricians towards
      caesarean delivery in rural Bangladesh.
AB  - BACKGROUND: Caesarean section is a lifesaving surgical intervention for women and
      their newborns, though overutilization is a public health concern. The caesarean
      rate in Bangladesh is approximately 23% overall, and in private facilities it is
      over 70%. It is essential to know both the supply side (obstetricians) and demand
      side (parturient women) views on caesarean birth in order to formulate specific
      interventions to address the escalating rate of caesareans. METHODS: This
      qualitative study took place in Matlab, a rural sub-district in Bangladesh. We
      interviewed women attending their 3rd antenatal visit, those with recent
      caesareans, and obstetricians from both public and private health facilities. In
      total there were twenty in-depth interviews and four focus group discussions.
      Study participants were asked about their preferences on birthing mode and
      knowledge of the caesarean section process. Thematic data analysis was done
      following a deductive approach. RESULTS: Women from this rural community had a
      strong preference for normal vaginal birth. However, they were willing to accept
      the attending health care provider's decision for caesarean birth. Antenatal care
      sessions did not provide information on the medical indications for caesarean
      section. Furthermore, some women had the misconception that episiotomy itself is
      a 'small caesarean.' Primary health care providers and clinic agents (brokers)
      had a strong influence on women's decision to choose a health facility for giving
      birth. However, obstetricians, having a preference for caesarean section, were
      receiving more patients from these brokers which may be an important reason for
      the high rate of clinically non-indicated caesareans at private hospitals in
      Bangladesh. Improper labour monitoring and inadequate staffing at health
      facilities were additional influences on the preference for caesarean section.
      However, critical knowledge gaps were also observed among study obstetricians,
      particularly with regards to the indications for and timing of elective caesarean
      sections. CONCLUSION: There is a need to educate women about the advantages and
      disadvantages of different birthing modes to ensure their active participation in
      the decision making process. Strong policy regulations are needed to ensure
      legitimate decision making by obstetricians regarding mode of birthing.

PMID- 30208873
TI  - Transcreation: an implementation science framework for community-engaged
      behavioral interventions to reduce health disparities.
AB  - BACKGROUND: Methods for translating evidence-based behavioral interventions into
      real-world settings seldom account for the special issues in reaching health
      disparity populations. MAIN TEXT: The objective of this article is to describe an
      innovative "transcreational" framework for designing and delivering interventions
      in communities to reduce health disparities. We define transcreation as the
      process of planning, delivering, and evaluating interventions so that they
      resonate with the community experiencing health disparities, while achieving
      intended health outcomes. The Transcreation Framework for Community-engaged
      Behavioral Interventions to Reduce Health Disparities comprises seven steps: 1)
      identify community infrastructure and engage partners; 2) specify theory; 3)
      identify multiple inputs for new program; 4) design intervention prototype; 5)
      design study, methods, and measures for community setting; 6) build community
      capacity for delivery; and 7) deliver transcreated intervention and evaluate
      implementation processes. Communities are engaged from the start and
      interventions are delivered by community-based interventionists and tested in
      community settings. The framework applies rigorous scientific methods for
      evaluating program effectiveness and implementation processes. It incorporates
      training and ongoing technical assistance to assure treatment fidelity and build
      community capacity. CONCLUSIONS: This framework expands the types of scientific
      evidence used and balances fidelity to evidence and fit to the community setting.
      It can guide researchers and communities in developing and testing behavioral
      interventions to reduce health disparities that are likely to be sustained
      because infrastructure development is embedded in the research.

PMID- 30208875
TI  - A metagenome-wide association study of gut microbiota in asthma in UK adults.
AB  - BACKGROUND: Asthma, one of the most common chronic respiratory disorders, is
      associated with the hyper-activation of the T-cell subset of adaptive immunity.
      The gut microbiota may be involved in the development of asthma through the
      production of short-chain fatty acids (SCFAs), exhibiting modulatory effects on
      Th. So, we performed a metagenome-wide association study (MWAS) of the fecal
      microbiota from individuals with asthma and healthy controls. And that was the
      first case to resolve the relationship between asthma and microbiome among UK
      adults. RESULTS: The microbiota of the individuals with asthma consisted of fewer
      microbial entities than the microbiota of healthy individuals. Faecalibacterium
      prausnitzii, Sutterella wadsworthensis and Bacteroides stercoris were depleted in
      cases, whereas Clostridiums with Eggerthella lenta were over-represented in
      individuals with asthma. Functional analysis shows that the SCFAs might be
      altered in the microbiota of asthma patients. CONCLUSION: In all, the adult human
      gut microbiome of asthma patients is clearly different from healthy controls. The
      functional and taxa results showed that the change of asthma patients might
      related to SCFAs.

PMID- 30208877
TI  - Global Abortion Policies Database: a new approach to strengthening knowledge on
      laws, policies, and human rights standards.
AB  - BACKGROUND: The Global Abortion Policies Database (GAPD), launched in June 2017,
      provides a verifiable, comprehensive, nuanced approach to information and data
      sources on abortion law and policy. Abortion laws, policies, and guidelines from
      United Nations (UN) and World Health Organization (WHO) Member States are
      juxtaposed to information and recommendations from WHO safe abortion guidance,
      national sexual and reproductive health indicators, and relevant UN human rights
      bodies' concluding observations to countries. MAIN BODY: The Global Abortion
      Policies Database aims to increase transparency of information and accountability
      of states for the protection of individuals' health and human rights. The
      database presents current information on abortion laws and policies that goes
      beyond categories of lawful abortion to include information on additional access
      requirements, service provision, conscientious objection, and penalties. Wide
      ranging variations among countries' legal requirements and criminal penalties
      raise questions about the evidentiary and human rights basis for abortion laws
      and policies. Source documents found in the database highlight that in many
      jurisdictions legal and policy guidance is either non-existent, not clear, or
      conflicting. By juxtaposing a jurisdiction's abortion laws and policies to
      relevant WHO guidance and by facilitating comparisons of countries' sexual and
      reproductive health indicators, the database can enable deep policy analysis of
      states' obligations to meet the health needs and human rights of individuals in
      the context of abortion. Policy analysis in the context of authoritative guidance
      on human rights standards can enable health and rights advocates to hold
      governments accountable for respecting, protecting, and fulfilling individuals'
      human rights. CONCLUSION: The GAPD is a comprehensive tool that can be used to
      strengthen knowledge, inform law and policy research to generate evidence on the
      impact of laws and policies in practice, and facilitate greater awareness of the
      many challenges to creating enabling policy environments for safe abortion.

PMID- 30208876
TI  - Mapping the impact of the expanded Mexico City Policy for HIV/ family planning
      service integration in PEPFAR-supported countries: a risk index.
AB  - BACKGROUND: The previously-named Mexico City Policy (MCP) - which prohibited non
      U.S.-based non-governmental organizations (NGOs) from receiving U.S. family
      planning (FP) funding if they advocated, provided, counseled, or referred clients
      for abortions, even with non-U.S. funds - was reinstated and expanded in 2017.
      For the first time, the expanded MCP (EMCP) applies to HIV funding through the
      President's Emergency Plan for AIDS Relief (PEPFAR) in addition to FP funding.
      Previous, and more limited, iterations of the policy forced clinic closures and
      decreased contraceptive access, prompting the need to examine where and how the
      EMCP may impact FP/HIV service integration. METHODS: The likelihood of FP/HIV
      service de-integration under the EMCP was quantified using a composite risk index
      for 31 PEPFAR-funded countries. The index combines six standardized indicators
      from publically available sources organized into three sub-indexes: 1) The
      importance of PEPFAR for in-country service delivery of HIV and FP services; 2)
      The susceptibility of implementing partners to the EMCP; and 3) The integration
      of FP/HIV funds and programming through PEPFAR and USAID. RESULTS: Countries with
      the highest overall risk scores included Zambia (3.3) Cambodia (3.2), Uganda
      (3.1), South Africa (2.9), Haiti (2.8), Lesotho (2.8), Swaziland (2.1), and
      Burundi (1.5). Zambia's risk score is driven by sub-index 1, having a high
      proportion of country HIV expenditures provided by PEPFAR (86.3%). Cambodia and
      Uganda's scores are driven sub-index 3, with both countries reporting 100% of
      PEPFAR supported HIV delivery sites were providing integrated FP services in
      2017. South Africa's risk score is driven by sub-index 2, where roughly 60% of
      PEPFAR funding is to non U.S.-based NGOs. Of the countries with the highest risk
      scores, Swaziland, Lesotho, and South Africa, are also in the top quartile of
      PEPFAR countries for HIV prevalence and unintended pregnancies among young women.
      CONCLUSION: This analysis highlights where and why the EMCP may have the greatest
      impact on FP/HIV service integration. The possible disruption of service
      integration in countries with generalized HIV epidemics highlights significant
      risks. Researchers, national governments, and non-U.S. funders can consider these
      risk factors to help target their responses to the EMCP and mitigate potential
      harms of the policy.

PMID- 30208878
TI  - GNPTAB c.2404C > T nonsense mutation in a patient with mucolipidosis III
      alpha/beta: a case report.
AB  - BACKGROUND: Mucolipidosis alpha/beta is an inborn error of metabolism
      characterized by deficiency of GlcNAc-1-phosphotransferase, in which essential
      alpha/beta subunits are encoded by the GNPTAB gene. The autosomal recessive
      condition is due to disruptions of hydrolase mannose 6-phosphate marker
      generation, defective lysosomal targeting and subsequent intracellular
      accumulation of non-degraded material. Clinical severity depends on residual
      GlcNAc-1-phosphotransferase activity, which distinguishes between the milder type
      III disease and the severe, neonatal onset type II disease. CASE PRESENTATION: We
      report the clinical, biochemical and genetic diagnosis of mucolipidosis III
      alpha/beta in a two-year-old Chinese boy who initially presented with poor weight
      gain, microcephaly and increased tone. He was confirmed to harbor the common
      splice site mutation c.2715 + 1G > A and the nonsense variant c.2404C > T
      (p.Q802*). Clinically, the patient had multiple phenotypic features typical of
      mucopolysaccharidosis including joint contractures, coarse facial features, kypho
      lordosis, pectus carinatum and umbilical hernia. However, the relatively mild
      developmental delay compared to severe type I and type II mucopolysaccharidosis
      and the absence of macrocephaly raised the possibility of the less commonly
      diagnosed mucolipidosis alpha/beta. Critical roles of lysosomal enzyme activity
      assay, which showed elevated alpha-iduronidase, iduronate sulfatase, galactose-6
      sulphate sulphatase, arylsulfatase B and alpha-hexosaminidase activities; and
      genetic study, which confirmed the parental origin of both mutations, were
      highlighted. CONCLUSIONS: The recently reported nonsense variant c.2404C > T in
      the GNPTAB gene is further recognized and this contributes to the genotype
      phenotype spectrum of mucolipidosis alpha/beta.

PMID- 30208879
TI  - Expression of alternatively spliced variants of the Dclk1 gene is regulated by
      psychotropic drugs.
AB  - BACKGROUND: The long-term effects of psychotropic drugs are associated with the
      reversal of disease-related alterations through the reorganization and
      normalization of neuronal connections. Molecular factors that trigger drug
      induced brain plasticity remain only partly understood. Doublecortin-like kinase
      1 (Dclk1) possesses microtubule-polymerizing activity during synaptic plasticity
      and neurogenesis. However, the Dclk1 gene shows a complex profile of
      transcriptional regulation, with two alternative promoters and exon splicing
      patterns that suggest the expression of multiple isoforms with different kinase
      activities. RESULTS: Here, we applied next-generation sequencing to analyze
      changes in the expression of Dclk1 gene isoforms in the brain in response to
      several psychoactive drugs with diverse pharmacological mechanisms of action. We
      used bioinformatics tools to define the range and levels of Dclk1 transcriptional
      regulation in the mouse nucleus accumbens and prefrontal cortex. We also sought
      to investigate the presence of DCLK1-derived peptides using mass spectrometry. We
      detected 15 transcripts expressed from the Dclk1 locus (FPKM > 1), including 2
      drug-regulated variants (fold change > 2). Drugs that act on serotonin receptors
      (5-HT2A/C) regulate a subset of Dclk1 isoforms in a brain-region-specific manner.
      The strongest influence was observed for the mianserin-induced expression of an
      isoform with intron retention. The drug-activated expression of novel alternative
      Dclk1 isoforms was validated using qPCR. The drug-regulated isoform contains
      genetic variants of DCLK1 that have been previously associated with schizophrenia
      and hyperactivity disorder in humans. We identified a short peptide that might
      originate from the novel DCLK1 protein product. Moreover, protein domains encoded
      by the regulated variant indicate their potential involvement in the negative
      regulation of the canonical DCLK1 protein. CONCLUSIONS: In summary, we identified
      novel isoforms of the neuroplasticity-related gene Dclk1 that are expressed in
      the brain in response to psychotropic drug treatments.

PMID- 30208880
TI  - Cross-contamination in canine and feline dietetic limited-antigen wet diets.
AB  - BACKGROUND: Adverse food reactions (AFRs) are defined as abnormal responses to an
      ingested food or food additive. Diagnosis and treatment of AFRs consist of the
      complete elimination of these ingredients in the dietary trial. Previous studies
      have demonstrated the presence of undeclared ingredients in commercial limited
      antigen dry food diets that can compromise the results and efficacy of dietary
      elimination trails. The aim of this study was to assess a selection of commercial
      canine and feline dietetic limited-antigen wet foods for the potential cross
      contamination of animal proteins from origins not mentioned on the label.
      RESULTS: Eleven canine and feline dietetic limited-antigen wet foods (9 novel
      animal protein foods, 1 vegetarian and 1 hydrolyzed) were analyzed by polymerase
      chain reaction (PCR) to detect the presence DNA of animal and vegetal origins.
      PCR analysis confirmed the contamination of 6 of the 11 (54.5%) limited-antigen
      wet diets with undeclared animal protein. One of these 6 diets was solely
      composed of animal protein sources completely unrelated to those declared on the
      label. None of the foods containing horse meat or fish were contaminated, and
      neither were the vegetarian or the hydrolyzed food products. Moreover, the
      results show that had zoological class primers only been used to check for cross
      class contaminations, as are generally used in the pet food industry for in-house
      checks, the apparent contamination rate would have been significantly
      underestimated: less than 20% (3/11), instead of the actual rate of 54.7% using
      species-specific primers. CONCLUSION: This study reveals a high rate of cross
      contamination in dietetic limited-antigen wet canine and feline foods, as
      previously described for dietetic dry limited-antigen foods (reported to be more
      than 80%). These results add new fuel to the discussion about the potential
      causes underlying the failure of elimination diets, since animal protein
      contaminants may actually be present in the commercial dietetic limited-antigen
      diets. AFRs may therefore occur as a result of inadequate practices in the pet
      food industry.

PMID- 30208881
TI  - A large, international study on post-transplant glomerular diseases: the TANGO
      project.
AB  - BACKGROUND: Long-term outcomes in kidney transplantation (KT) have not
      significantly improved during the past twenty years. Despite being a leading
      cause of graft failure, glomerular disease (GD) recurrence remains poorly
      understood, due to heterogeneity in disease pathogenesis and clinical
      presentation, reliance on histopathology to confirm disease recurrence, and the
      low incidence of individual GD subtypes. Large, international cohorts of patients
      with GD are urgently needed to better understand the disease pathophysiology,
      predictors of recurrence, and response to therapy. METHODS: The Post-TrANsplant
      GlOmerular Disease (TANGO) study is an observational, multicenter cohort study
      initiated in January 2017 that aims to: 1) characterize the natural history of GD
      after KT, 2) create a biorepository of saliva, blood, urine, stools and kidney
      tissue samples, and 3) establish a network of patients and centers to support
      novel therapeutic trials. The study includes 15 centers in America and Europe.
      Enrollment is open to patients with biopsy-proven GD prior to transplantation,
      including IgA nephropathy, membranous nephropathy, focal and segmental
      glomerulosclerosis, atypical hemolytic uremic syndrome, dense-deposit disease, C3
      glomerulopathy, complement- and IgG-positive membranoproliferative
      glomerulonephritis or membranoproliferative glomerulonephritis type I-III (old
      classification). During phase 1, patient data will be collected in an online
      database. The biorepository (phase 2) will involve collection of samples from
      patients for identification of predictors of recurrence, biomarkers of disease
      activity or response to therapy, and novel pathogenic mechanisms. Finally,
      through phase 3, we will use our multicenter network of patients and centers to
      launch interventional studies. DISCUSSION: Most prior studies of post-transplant
      GD recurrence are single-center and retrospective, or rely upon registry data
      that frequently misclassify the cause of kidney disease. Systematically
      determining GD recurrence rates and predictors of clinical outcomes is essential
      to improving post-transplant outcomes. Furthermore, accurate molecular
      phenotyping and biomarker development will allow better understanding of
      individual GD pathogenesis, and potentially identify novel drug targets for GD in
      both native and transplanted kidneys. The TANGO study has the potential to tackle
      GD recurrence through a multicenter design and a comprehensive biorepository.

PMID- 30208882
TI  - Genetically determined high activities of the TNF-alpha, IL23/IL17, and NFkB
      pathways were associated with increased risk of ankylosing spondylitis.
AB  - BACKGROUND: Ankylosing spondylitis (AS) results from the combined effects of
      susceptibility genes and environmental factors. Polymorphisms in genes regulating
      inflammation may explain part of the heritability of AS. METHODS: Using a
      candidate gene approach in this case-control study, 51 mainly functional single
      nucleotide polymorphisms (SNPs) in genes regulating inflammation were assessed in
      709 patients with AS and 795 controls. Data on the patients with AS were obtained
      from the DANBIO registry where patients from all of Denmark are monitored in
      routine care during treatment with conventional and biologic disease modifying
      anti-rheumatic drugs (bDMARDs). The results were analyzed using logistic
      regression (adjusted for age and sex). RESULTS: Nine polymorphisms were
      associated with risk of AS (p < 0.05). The polymorphisms were in genes regulating
      a: the TNF-alpha pathway (TNF -308 G > A (rs1800629), and - 238 G > A (rs361525);
      TNFRSF1A -609 G > T (rs4149570), and PTPN22 1858 G > A (rs2476601)), b: the
      IL23/IL17 pathway (IL23R G > A (rs11209026), and IL18-137 G > C (rs187238)), or
      c: the NFkB pathway (TLR1 743 T > C (rs4833095), TLR4 T > C (rs1554973), and LY96
      1625 C > G (rs11465996)). After Bonferroni correction the homozygous variant
      genotype of TLR1 743 T > C (rs4833095) (odds ratios (OR): 2.59, 95% confidence
      interval (CI): 1.48-4.51, p = 0.04), and TNFRSF1A -609 G > T (rs4149570) (OR:
      1.79, 95% CI: 1.31-2.41, p = 0.01) were associated with increased risk of AS and
      the combined homozygous and heterozygous variant genotypes of TNF -308 G > A
      (rs1800629) (OR: 0.56, 95% CI: 0.44-0.72, p = 0.0002) were associated with
      reduced risk of AS. CONCLUSION: We replicated associations between AS and the
      polymorphisms in TNF (rs1800629), TNFRSF1A (rs4149570), and IL23R (rs11209026).
      Furthermore, we identified novel risk loci in TNF (rs361525), IL18 (rs187238),
      TLR1 (rs4833095), TLR4 (rs1554973), and LY96 (rs11465996) that need validation in
      independent cohorts. The results suggest that genetically determined high
      activity of the TNF-alpha, IL23/IL17, and NFkB pathways increase risk of AS.

PMID- 30208884
TI  - Variation in the health outcomes associated with frailty among home care clients:
      relevance of caregiver distress and client sex.
AB  - BACKGROUND: The identification of contextual factors that modify associations
      between client frailty and their health and service use outcomes is essential for
      informed home health care and policy planning. Our objective was to examine
      variation in the associations between frailty and select 1-year health outcomes
      by caregiver distress and client sex among community-residing older care
      recipients. METHODS: We conducted a retrospective cohort study using linked
      population-based clinical and health administrative databases for all long-stay
      home care clients (n = 234,552) aged 66+ years assessed during April 2010-2013 in
      Ontario, Canada. Frailty was assessed using a previously validated 72-item
      frailty index (FI). Presence of caregiver distress was derived from clinical
      assessment items administered by trained home care assessors. Multivariable log
      binomial regression models were used to examine variations in the associations
      between frailty and outcomes of interest (mortality, nursing home [NH] placement,
      all-cause and prolonged hospitalization) by caregiver distress, with further
      model stratification by client sex. RESULTS: Frailty prevalence varied little by
      sex (19.3% women, 19.9% men) despite significant sex-differences in clients'
      sociodemographic and health characteristics. In both sexes, frailty was
      significantly associated with all outcomes, particularly NH placement (RR = 3.84,
      95%CI 3.75-3.93) and death (RR = 2.32, 95%CI 2.27-2.37), though risk ratios were
      greater for women. Caregiver distress was more common with increasing frailty and
      for male clients, and a significant independent predictor of NH placement and
      prolonged hospitalization in both sexes. The association between frailty and NH
      placement (but not other outcomes) varied by caregiver distress for both men and
      women (p < 0.001 interaction terms), showing a greater magnitude of association
      among clients without (vs. with) a distressed caregiver. CONCLUSIONS: As
      caregiver distress varies by client sex, represents a key driver of NH placement
      (even among relatively robust clients), and modifies the impact of other risk
      factors such as frailty, it should be routinely assessed. Further, sex
      differences should be considered when developing and evaluating community-based
      services for older adults and their caregivers.

PMID- 30208883
TI  - Novel insights into the host immune response of chicken Harderian gland tissue
      during Newcastle disease virus infection and heat treatment.
AB  - BACKGROUND: Newcastle disease virus, in its most pathogenic form, threatens the
      livelihood of rural poultry farmers where there is a limited infrastructure and
      service for vaccinations to prevent outbreaks of the virus. Previously reported
      studies on the host response to Newcastle disease in chickens have not examined
      the disease under abiotic stressors, such as heat, which commonly experienced by
      chickens in regions such as Africa. The objective of this study was to elucidate
      the underlying biological mechanisms that contribute to disease resistance in
      chickens to the Newcastle disease virus while under the effects of heat stress.
      RESULTS: Differential gene expression analysis identified genes differentially
      expressed between treated and non-treated birds across three time points (2, 6,
      and 10 days post-infection) in Fayoumi and Leghorn birds. Across the three time
      points, Fayoumi had very few genes differentially expressed between treated and
      non-treated groups at 2 and 6 days post-infection. However, 202 genes were
      differentially expressed at 10 days post-infection. Alternatively, Leghorn had
      very few genes differentially expressed at 2 and 10 days post-infection but had
      167 differentially expressed genes at 6 days post-infection. Very few
      differentially expressed genes were shared between the two genetic lines, and
      pathway analysis found unique signaling pathways specific to each genetic line.
      Fayoumi had significantly lower viral load, higher viral clearance, higher anti
      NDV antibody levels, and fewer viral transcripts detected compared to Leghorns.
      Fayoumis activated immune related pathways including SAPK/JNK and p38 MAPK
      signaling pathways at earlier time points, while Leghorn would activate these
      same pathways at a later time. Further analysis revealed activation of the GP6
      signaling pathway that may be responsible for the susceptible Leghorn response.
      CONCLUSIONS: The findings in this study confirmed our hypothesis that the Fayoumi
      line was more resistant to Newcastle disease virus infection compared to the
      Leghorn line. Within line and interaction analysis demonstrated substantial
      differences in response patterns between the two genetic lines that was not
      observed from the within line contrasts. This study has provided novel insights
      into the transcriptome response of the Harderian gland tissue during Newcastle
      disease virus infection while under heat stress utilizing a unique resistant and
      susceptible model.

PMID- 30208885
TI  - Establishment of fluoroscopy views and standardized procedure of percutaneous
      magic screw insertion for acetabulum fractures.
AB  - BACKGROUND: To place the magic screw more simply, we established a set of
      reproducible fluoroscopic views and a standardized procedure of magic screw
      insertion. MATERIALS AND METHODS: This study on the magic screw tunnel uses a
      three-dimensional reconstruction model and a skeleton projection. The 3D model of
      the pelvis was made to be transparent and it was rotated to the place where the
      ischial spine was just sheltered by the posterior wall of the acetabulum. The
      angles of this view projection were recorded in the transverse plane and coronal
      plane. Six cadaveric pelvises (three males, three female) were used to validate
      the proper projection angle of the C-arm fluoroscopy. The skeleton specimens were
      all positioned latericumbent on a radiolucent table. RESULT: In all pelvis 3D
      models, all magic cylinders with a 7.3 mm diameter were successfully inserted
      along the bone structure tunnel in 30 3D pelvic models. The average angle of the
      transverse view rotated by the C-arm fluoroscopy was 162 degrees  in males and
      157 degrees  in females, the angle of the coronal plane was 22 degrees  in males
      and 24 degrees  in females. The average distance between the front wheel of the C
      arm machine and the middle axial line of the radiolucent bed was 43 cm in males
      and 43 cm in females. In skeleton pelvis research, all the screws were safely
      inserted using this method. CONCLUSION: The magic screw technique could be a good
      choice for the treatment of acetabular fractures, especially quadrilateral plate
      fractures. If the proper fluoroscopy view technique is used properly, the magic
      screw can be inserted rapidly and safely.

PMID- 30208887
TI  - Validation of the Jefferson Scale of Physician Empathy in Spanish medical
      students who participated in an Early Clerkship Immersion programme.
AB  - BACKGROUND: The Jefferson Scale of Physician Empathy is the most widely used
      instrument to measure empathy in the doctor-patient relationship. This work
      pursued cultural adaptation and validation of the original scale, in its health
      professions version (JSE-HP), for medical students who participate in an Early
      Clerkship Immersion Programme of a Spanish university. METHODS: The questionnaire
      was replied by 506 1st, 2nd, 3rd and 5th year medical students from Universidad
      Francisco de Vitoria, Madrid, in 2014 and 2016. Internal consistency was analysed
      by means of Cronbach's alpha, and reliability by means of test-retest using the
      intraclass correlation coefficient and the Bland-Altman method. The construct
      validity was checked by means of confirmatory factor analysis and association
      with other empathy-related variables. Criterion validity was compared using
      Davis' Interpersonal Reactivity Index. RESULTS: Cronbach's alpha was 0.82 (range
      0.80-0.85). Item-total score correlations were positive and significant (median
      0.45, p <  0.01). The test-retest intraclass correlation coefficient was 0.68
      (0.42-0.82). The factor analysis confirmed the three original factors:
      "perspective taking", "compassionate care" and "standing in the patient's shoes".
      Women and students who preferred specialities focused on persons obtained the
      best scores. The JSE-HP scores were positively correlated with Interpersonal
      Reactivity Index, personality traits were associated with empathy, clinical
      interview skills and Objective Structured Clinical Examinations. CONCLUSION: The
      results support the validity and reliability of JSE-HP applied to Spanish medical
      students.

PMID- 30208886
TI  - Smoking is associated with quantifiable differences in the human lung DNA virome
      and metabolome.
AB  - BACKGROUND: The role of commensal viruses in humans is poorly understood, and the
      impact of the virome on lung health and smoking-related disease is particularly
      understudied. METHODS: Genetic material from acellular bronchoalveolar lavage
      fluid was sequenced to identify and quantify viral members of the lower
      respiratory tract which were compared against concurrent bronchoalveolar lavage
      bacterial, metabolite, cytokine and cellular profiles, and clinical data. Twenty
      smoker and 10 nonsmoker participants with no significant comorbidities were
      studied. RESULTS: Viruses that infect bacteria (phages) represented the vast
      majority of viruses in the lung. Though bacterial communities were statistically
      indistinguishable across smokers and nonsmokers as observed in previous studies,
      lung viromes and metabolic profiles were significantly different between groups.
      Statistical analyses revealed that changes in viral communities correlate most
      with changes in levels of arachidonic acid and IL-8, both potentially relevant
      for chronic obstructive pulmonary disease (COPD) pathogenesis based on prior
      studies. CONCLUSIONS: Our assessment of human lung DNA viral communities reveals
      that commensal viruses are present in the lower respiratory tract and differ
      between smokers and nonsmokers. The associations between viral populations and
      local immune and metabolic tone suggest a significant role for virome-host
      interaction in smoking related lung disease.

PMID- 30208889
TI  - DEDICATE: proposal for a conceptual framework to develop dementia-friendly
      integrated eCare support.
AB  - BACKGROUND: Evidence shows that the implementation of information and
      communication technologies (ICT) enabled services supporting integrated dementia
      care represents an opportunity that faces multi-pronged challenges. First, the
      provision of dementia support is fragmented and often inappropriate. Second,
      available ICT solutions in this field do not address the full spectrum of support
      needs arising across an individual's whole dementia journey. Current solutions
      fail to harness the potential of available validated e-health services, such as
      telehealth and telecare, for the purposes of dementia care. Third, there is a
      lack of understanding of how viable business models in this field can operate.
      The field comprises both professional and non-professional players that interact
      and have roles to play in ensuring that useful technologies are developed,
      implemented and used. METHODS: Starting from a literature review, including
      relevant pilot projects for ICT-based dementia care, we define the major
      requirements of a system able to overcome the limitations evidenced in the
      literature, and how this system should be integrated in the socio-technical
      ecosystem characterizing this disease. From here, we define the DEDICATE
      architecture of such a system, and the conceptual framework mapping the
      architecture over the requirements. RESULTS: We identified three macro
      requirements, namely the need to overcome: deficient technology innovation,
      deficient service process innovation, and deficient business models innovation.
      The proposed architecture is a three level architecture in which the center (data
      layer) includes patients' and informal caregivers' preferences, memories, and
      other personal data relevant to sustain the dementia journey, is connected
      through a middleware (service layer), which guarantees core IT services and
      integration, to dedicated applications (application layer) to sustain dementia
      care (formal support services, FSS), and to existing formal care infrastructures,
      in order to guarantee care coordination (care coordination services, CCS).
      CONCLUSIONS: The proposed DEDICATE architecture and framework envisages a
      feasible means to overcome the present barriers by: (1) developing and
      integrating technologies that can follow the patient and the caregivers
      throughout the development of the condition, since the early stages in which the
      patient is able to build up preferences and memories will be used in the later
      stages to maximise personalization and thereby improve efficacy and usability
      (technology innovation); (2) guaranteeing the care coordination between formal
      and informal caregivers, and giving an active yet supported role to the latter
      (service innovation); and (3) integrating existing infrastructures and care
      models to decrease the cost of the overall care pathway, by improving system
      interoperability (business model innovation).

PMID- 30208888
TI  - The association between total bilirubin and serum triglyceride in both sexes in
      Chinese.
AB  - OBJECTIVE: Dyslipidemia can cause some chronic diseases. Bilirubin is reported to
      have anti-inflammatory and anti-oxidant properties. We aimed to explore the
      relationship between triglyceride and total bilirubin (TB) in a large Chinese
      cohort. METHODS: A total of 80,298 healthy Chinese (48,971 male, 31,327 female)
      enrolled in this cross-sectional study. Clinical data were collected from
      participants. Database was divided according to sex and age. The relationship
      between triglyceride and TB was analyzed by quartiles of TB. Levels of
      triglyceride were compared in different TB subgroups by one-way analysis of
      variance and independent sample's t-test. Crude and adjusted odds ratios of
      triglyceride for TB with 95% confidence intervals were analyzed by binary
      logistic regression models. RESULTS: Overall, men showed higher levels of TB and
      triglyceride than women. In people older than 60 years, women had higher
      triglyceride levels than men. Linear logistic regression analyses showed a
      negative relationship between triglyceride and TB in both genders. Men showed
      significantly higher overall incidence of high triglyceride than women. Men less
      than 60 years old showed a higher incidence of high triglyceride. For women older
      than 60 years, the incidence of high triglyceride was higher. However, high TB
      showed no protective effects on both genders from high TG in the binary logistic
      regression models. TB showed a detrimental effect on high TG in model 2 which
      included TB as a covariate. But that effect disappeared after other confounding
      factors were included. CONCLUSIONS: Our findings showed no association between TB
      and triglyceride in Chinese.

PMID- 30208890
TI  - Equity and efficiency of primary health care resource allocation in mainland
      China.
AB  - BACKGROUND: China had proposed the unification of equity and efficiency since the
      launch of the new round of health system reform in 2009. And the central
      government gave priority to the development of primary health care (PHC) whilst
      ensuring its availability and improving its efficiency. This study aimed to
      evaluate the changes of equity and efficiency in PHC resource allocation (PHCRA)
      and explored ways to improve the current situation. METHODS: The data of this
      study came from the China Health Statistical Yearbook (2013-2017) and China
      Statistical Yearbook (2017). Three and five indicators were used to measure
      equity and efficiency, respectively. The Lorenz curve, Gini coefficient (G),
      Theil index (T) and health resource density index (HRDI) were used to assess
      equity in demographic and geographical dimensions. Data envelopment analysis
      (DEA) and the Malmquist productivity index (MPI) were chosen to measure the
      efficiency and productivity of PHCRA. RESULTS: From 2012 to 2016, the total
      amount of PHCR had increased year by year. The Gs by population size were below
      0.2 and that by geographical area were between 0.6 and 0.7. T had the same trend
      with G, and intra-regional contribution rates were higher than inter-regional
      contribution rates, which were all beyond 60%. From 2012 to 2016, the numbers of
      provinces that achieved an effective DEA were 4, 3, 4, 5 and 5, respectively. The
      mean of the total factor productivity index was 0.994. CONCLUSION: The equity of
      PHCRA in terms of population size is superior in the geographical area. Intra
      regional differences are the main source of inequality. The eastern region has
      the highest density of PHCR, whereas the western region has the lowest. In
      addition, PHC institutions in more than 80% of the provinces are inefficient, and
      the productivity of the institutions decline by 0.6% from 2012 to 2016 because of
      technological retrogression.

PMID- 30208893
TI  - Haemodynamic changes during propofol induction in dogs: new findings and approach
      of monitoring.
AB  - BACKGROUND: Propofol is one of the most widely used injectable anaesthetic agents
      in veterinary practice. Cardiovascular effects related to propofol use in dogs
      remain less well defined. The main objective of this study was to evaluate the
      haemodynamic changes during induction of general anaesthesia with propofol in
      healthy dogs, by a beat-to-beat continuous monitoring. All dogs were premedicated
      with intramuscular acepromazine (0.015 mg/kg) and methadone (0.15 mg/kg).
      Transthoracic echocardiography was used to measure the velocity time integral
      (VTI) of the left ventricular outflow tract. A syringe driver, programmed to
      deliver propofol 5 mg/kg over 30 s followed by a continuous infusion of 25
      mg/kg/h, was used to induce and maintain anaesthesia. From the initiation of
      propofol administration, heart rate (HR) and mean invasive arterial blood
      pressure (MAP) were recorded every 5 s for 300 s, while aortic blood flow was
      continuously recorded and stored for 300 S. maximum cardiovascular depression was
      defined the lowest MAP (MAP_Tpeak) recorded during the monitored interval. VTI
      and VTI*HR were calculated at 0, 30, 90, 120, 150 and 300 s post administration
      of propofol, and at MAP_Tpeak. Haemodynamic effects of propofol in relation to
      plasma and biophase concentrations were also evaluated by pharmacokinetics
      simulation. RESULTS: The median (range) HR was significantly higher (p = 0.006)
      at the moment of maximum hemodynamic depression (Tpeak) [105(70-148) bpm]
      compared with pre-induction values (T0) [65(50-120) bpm]. The median (range) MAP
      was significantly lower (p < 0.001) at Tpeak [61(51-69) mmHg] compared with T0
      [88(72-97) mmHg]. The median (range) VTI and VTI*HR were similar at the two time
      points [11.9(8.1-17.3) vs 13,3(9,4-16,5) cm, and 1172(806-1554) vs 1002(630-1159)
      cm*bpm, respectively]. CONCLUSIONS: Induction of anaesthesia with propofol causes
      a drop of arterial pressure in healthy dogs, however cardiac output is well
      maintained by compensatory chronotropic response. The magnitude of MAP_Tpeak may
      be strictly related with propofol plasma concentration.

PMID- 30208892
TI  - Ocular surface health in Shanghai University students: a cross-sectional study.
AB  - BACKGROUND: Our study aimed to investigate the ocular surface health of Shanghai
      University students. METHODS: This is a cross-sectional study carried out among
      freshmen and sophomores on the main campus of Shanghai University. Questionnaires
      including the widely-used ocular surface disease index (OSDI) and the Zung Self
      rating Anxiety Scale (SAS) were completed first, and then ocular examinations
      were conducted regarding height & weight, blood pressure and heart rate,
      optometry, intraocular pressure exam, vision and subjective refraction, Aladdin,
      Macular pigment density measurement, tear test, anterior segment examination,
      fundus photography, ophthalmologist check, TOPCON OCT check, and Collin's fundus
      blood test. RESULTS: Totally 901 students were involved in our five-day study.
      The prevalence of myopia was 92% (the spherical equivalent refraction (SER) < -
      0.50 D), and that of high myopia was 23% (SER < - 6.0D). The prevalence of dry
      eye disease (DED) was 10%. The corneal epithelial loss rate (corneal fluorescein
      staining > 1) was 10%, and corneal sensation decline rate (<= 30 mm) was 12%.
      4.5% of subjects (n = 40) had moderate or severe anxiety, 78% were mild and a
      small portion (17.5%) didn't have anxiety at all. No statistical significant
      association was found between anxiety with DED, fluorescein staining or with
      corneal sensation (all p > 0.05). However, subjects with DED had more symptoms of
      anxiety. Results also showed that students who kept eye strain for a long time
      were more inclined to have DED (12.5%: 6.9%, p = 0.0407, 95% CI); those who
      watched mobile phones and/or computers for over eight hours daily were more
      vulnerable to DED and fluorescein staining than others (14.1%: 8.6%, p = 0.0129;
      13.0%: 8.3%, p = 0.0233, 95% CI). CONCLUSIONS: Keeping eye strain or near work
      for a long time is associated with DED, while students with DED tend to encounter
      anxiety symptoms. The prevalence of myopia in Chinese university students is
      still high. We consider it necessary to provide education to university students
      about the good eye-using habits, and to diagnose anxiety for student patients
      with DED.

PMID- 30208891
TI  - Expression of selected genes isolated from whole blood, liver and obex in lambs
      with experimental classical scrapie and healthy controls, showing a systemic
      innate immune response at the clinical end-stage.
AB  - BACKGROUND: Incubation period, disease progression, pathology and clinical
      presentation of classical scrapie in sheep are highly dependent on PRNP genotype,
      time and route of inoculation and prion strain. Our experimental model with pre
      colostrum inoculation of homozygous VRQ lambs has shown to be an effective model
      with extensive PrPSc dissemination in lymphatic tissue and a short incubation
      period with severe clinical disease. Serum protein analysis has shown an
      elevation of acute phase proteins in the clinical stages of this experimental
      model, and here, we investigate changes in gene expression in whole blood, liver
      and brain. RESULTS: The animals in the scrapie group showed severe signs of
      illness 22 weeks post inoculation necessitating euthanasia at 23 weeks post
      inoculation. This severe clinical presentation was accompanied by changes in
      expression of several genes. The following genes were differentially expressed in
      whole blood: TLR2, TLR4, C3, IL1B, LF and SAA, in liver tissue, the following
      genes differentially expressed: TNF-alpha, SAA, HP, CP, AAT, TTR and TF, and in
      the brain tissue, the following genes were differentially expressed: HP, CP, ALB
      and TTR. CONCLUSIONS: We report a strong and evident transcriptional innate
      immune response in the terminal stage of classical scrapie in these animals. The
      PRNP genotype and time of inoculation are believed to contribute to the clinical
      presentation, including the extensive dissemination of PrPSc throughout the
      lymphatic tissue.

PMID- 30208894
TI  - Comparison of left ventricular strains and torsion derived from feature tracking
      and DENSE CMR.
AB  - BACKGROUND: Cardiovascular magnetic resonance (CMR) feature tracking is
      increasingly used to quantify cardiac mechanics from cine CMR imaging, although
      validation against reference standard techniques has been limited. Furthermore,
      studies have suggested that commonly-derived metrics, such as peak global strain
      (reported in 63% of feature tracking studies), can be quantified using contours
      from just two frames - end-diastole (ED) and end-systole (ES) - without requiring
      tracking software. We hypothesized that mechanics derived from feature tracking
      would not agree with those derived from a reference standard (displacement
      encoding with stimulated echoes (DENSE) imaging), and that peak strain from
      feature tracking would agree with that derived using simple processing of only ED
      and ES contours. METHODS: We retrospectively identified 88 participants with 186
      pairs of DENSE and balanced steady state free precession (bSSFP) image slices
      acquired at the same locations across two institutions. Left ventricular (LV)
      strains, torsion, and dyssynchrony were quantified from both feature tracking
      (TomTec Imaging Systems, Circle Cardiovascular Imaging) and DENSE. Contour-based
      strains from bSSFP images were derived from ED and ES contours. Agreement was
      assessed with Bland-Altman analyses and coefficients of variation (CoV). All
      biases are reported in absolute percentage. RESULTS: Comparison results were
      similar for both vendor packages (TomTec and Circle), and thus only TomTec
      Imaging System data are reported in the abstract for simplicity. Compared to
      DENSE, mid-ventricular circumferential strain (Ecc) from feature tracking had
      acceptable agreement (bias: - 0.4%, p = 0.36, CoV: 11%). However, feature
      tracking significantly overestimated the magnitude of Ecc at the base (bias: -
      4.0% absolute, p < 0.001, CoV: 18%) and apex (bias: - 2.4% absolute, p = 0.01,
      CoV: 15%), underestimated torsion (bias: - 1.4 deg/cm, p < 0.001, CoV: 41%), and
      overestimated dyssynchrony (bias: 26 ms, p < 0.001, CoV: 76%). Longitudinal
      strain (Ell) had borderline-acceptable agreement (bias: - 0.2%, p = 0.77, CoV:
      19%). Contour-based strains had excellent agreement with feature tracking
      (biases: - 1.3-0.2%, CoVs: 3-7%). CONCLUSION: Compared to DENSE as a reference
      standard, feature tracking was inaccurate for quantification of apical and basal
      LV circumferential strains, longitudinal strain, torsion, and dyssynchrony.
      Feature tracking was only accurate for quantification of mid LV circumferential
      strain. Moreover, feature tracking is unnecessary for quantification of whole
      slice strains (e.g. base, apex), since simplified processing of only ED and ES
      contours yields very similar results to those derived from feature tracking.
      Current feature tracking technology therefore has limited utility for
      quantification of cardiac mechanics.

PMID- 30208895
TI  - Prevalence of asymptomatic Plasmodium infections with sub-microscopic parasite
      densities in the northwestern border of Thailand: a potential threat to malaria
      elimination.
AB  - BACKGROUND: Asymptomatic infections with sub-microscopic Plasmodium serve as a
      silent reservoir of disease, critical to sustaining a low level of remanent
      malaria in the population. These infections must be effectively identified and
      targeted for elimination. The sensitivity of light microscopy, the traditional
      method used for diagnosing Plasmodium infections, is frequently insufficient for
      detecting asymptomatic infections due to the low density of parasitaemia. The
      objective of this study was to explore the current prevalence of asymptomatic sub
      microscopic Plasmodium carriages to evaluate the parasite reservoir amongst
      residents from 7 hamlets in Tak Province in northwestern Thailand using a highly
      sensitive molecular method. METHODS: Malaria infection was screened in a real
      world setting from 3650 finger-prick blood specimens collected in a mass cross
      sectional survey using light microscopy and loop-mediated isothermal
      amplification (LAMP). LAMP results were later confirmed in a laboratory setting
      in Bangkok using nested PCR, restriction enzyme digestion and DNA sequencing. The
      association of malaria infection with demographic factors was explored. RESULTS:
      Parasite prevalence was 0.27% (10/3650) as determined by microscopy. Sub
      microscopic infection prevalence was 2.33% (85/3650) by LAMP. Of these, 30.6%
      (26/85) were infected with Plasmodium falciparum, 52.9% (45/85) with Plasmodium
      vivax, 2.4% (2/85) with Plasmodium malariae, 4.7% (4/85) with mixed P. falciparum
      and P. vivax, and 9.4% (8/85) had parasite densities too low for species
      identification. Asymptomatic carriages (T < 37.5  degrees C) accounted for 95%
      (76/80) of all sub-microscopic cases with the highest prevalence occurring in the
      subjects 31-45 years of age (p <= 0.035). Participants working on plantations or
      as merchants had an increased infection risk. Evaluation by microscopy identified
      10.53% (10/95) of all Plasmodium infected participants. CONCLUSION: Participants
      carrying asymptomatic Plasmodium infections with sub-microscopic parasite
      densities are considerable in this area. These findings provide the true disease
      burden and risk factors in this region. This information helps to direct policy
      makers towards better schemes and delivery of targeted interventions. Moreover,
      this is the first study to use LAMP in mass screening for sub-clinical and sub
      microscopic infections in a field setting in Thailand. LAMP proves to be a
      sensitive and field-deployable assay suitable for national malaria control
      screening campaigns.

PMID- 30208896
TI  - 'I am always crying on the inside': a qualitative study on the implications of
      infertility on women's lives in urban Gambia.
AB  - BACKGROUND: There is an increasing awareness that infertility in Sub-Saharan
      Africa constitutes a severe social and public health problem. Few of the existing
      studies on infertility explicitly take into account the differences between
      women. However, how women experience infertility is formed by their various
      social positions. This research explores the implications of infertility on
      women's lives in urban Gambia and aims to provide an in-depth understanding of
      how this relates to gender and cultural norms as well as different social
      positions. METHODS: Qualitative data were collected through interviews (33),
      group discussions (13), participatory observations (14) and informal
      conversations (31). Purposive and snowball sampling techniques were used to
      identify participants. The data was analysed thematically using NVivo 11.
      RESULTS: Results showed that there was strong social pressure on urban women in
      The Gambia to procreate. Unable to conform to their gender role, women with
      infertility were confronted with financial problems, social stigma, as well as
      emotional and physical violence in their marriage. All women expressed feelings
      of trauma, stress and sadness. The intersectional approach used in this study
      highlighted how different positions influenced women's experiences of
      infertility. Urban women with a high socio-economic status had a more powerful
      position within their marriages and the broader community, due to their financial
      position, professional career and, sometimes, their educational background. In
      contrast, women from a lower socio-economic background were more likely to be
      harshly confronted with the social stigma of infertility. CONCLUSION: The lives
      of most women with infertility in The Gambia are characterized by social
      suffering resulting from gender and pro-natal norms, cultural beliefs and moral
      concerns, cultural practices and limited access to health care. An intersectional
      approach is an effective tool to inform public health and social policy since it
      highlights how, in specific situations, certain groups are more vulnerable than
      others.

PMID- 30208898
TI  - Environmental footprints of food consumption and dietary patterns among Lebanese
      adults: a cross-sectional study.
AB  - BACKGROUND: Following the release of the Sustainable Development Goals, dietary
      patterns and guidelines are being revised for their effect on the environment in
      addition to their health implications. The objective of this study was to
      evaluate and compare the Environmental Footprints (EFPs) of food consumption
      patterns among Lebanese adults. METHODS: For this study, data for adults aged >
      18 years (n = 337) were drawn from a previous national survey conducted in
      Lebanon (2008-2009), where dietary intake was assessed using a 61-item Food
      Frequency Questionnaire. Dietary patterns previously derived in the study sample
      included: Western, Lebanese-Mediterranean and High-Protein. In this study, food
      consumption and dietary patterns were examined for their EFPs including water
      use, energy use, and greenhouse gas (GHG) emissions, using review of life cycle
      analyses. RESULTS: In the study population, the EFPs of food consumption were:
      water use: 2571.62 +/- 1259.45 L/day; energy use: 37.34 +/- 19.98 MJ/day and
      GHGs: 4.06 +/- 1.93 kg CO2 eq / day. Among the three dietary patterns prevalent
      in the study population, the Lebanese-Mediterranean diet had the lowest water use
      and GHG per 1000 Kcal (Water (L/Kg): 443.61 +/- 197.15, 243.35 +/- 112.0, 264.72
      +/- 161.67; GHG (KG CO2 eq/day) 0.58 +/- 0.32, 0.38 +/- 0.24, 0.57 +/- 0.37, for
      the Western, Lebanese-Mediterranean and High- Protein, respectively). The scores
      of the High-Protein dietary pattern were associated with higher odds of the three
      EFPs, whereas the Lebanese-Mediterranean dietary pattern was associated with
      lower odds of energy use. Furthermore, scores of the Western pattern were
      associated with higher water use. CONCLUSIONS: The findings of this study showed
      that, among Lebanese adults, the Western and High-Protein dietary patterns had
      high EFPs, whereas the Lebanese-Mediterranean dietary pattern had lower water use
      and GHG emissions. Coupled to our earlier findings of the Lebanese-Mediterranean
      pattern's beneficial effects on health, the findings of this study lend evidence
      for the notion that what is healthy for people may also be healthy for ecosystems
      and highlight the need for nutrition recommendations to take into consideration
      the nexus of water, food, energy, in addition to health.

PMID- 30208897
TI  - "You can tell by the way I use my walk." Predicting the presence of cognitive
      load with gait measurements.
AB  - BACKGROUND: There is considerable evidence that a person's gait is affected by
      cognitive load. Research in this field has implications for understanding the
      relationship between motor control and neurological conditions in aging and
      clinical populations. Accordingly, this pilot study evaluates the cognitive load
      based on gait accelerometry measurements of the walking patterns of ten healthy
      individuals (18-35 years old). METHODS: Data points were collected using six
      triaxial accelerometer sensors and treadmill pressure reports. Stride and window
      extraction methods were used to process these data points and separate into
      statistical features. A binary classification was created by using logistic
      regression, support vector machine, random forest, and learning vector
      quantization to classify cognitive load vs. no cognitive load. RESULTS: Within
      and between subjects, a cognitive load was predicted with accuracy values ranged
      of 0.93-1 by all four models. Various feature selection methods demonstrated that
      only 2-20 variables could be used to achieve similar levels of accuracies.
      CONCLUSION: Coupling sensors with machine learning algorithms to detect the most
      minute changes in gait patterns, most of which are too subtle to identify with
      the human eye, may have a remarkable impact on the potential to detect potential
      neuromotor illnesses and fall risks. In doing so, we can open a new window to
      human health and safety prevention.

PMID- 30208900
TI  - The role of physical activity in the development of first cardiovascular disease
      event: a tree-structured survival analysis of the Danish ADDITION-PRO cohort.
AB  - BACKGROUND: Ambiguity exists in relation to the role of physical activity (PA)
      for cardiovascular disease (CVD) risk reduction. We examined the interplay
      between PA dimensions and more conventional CVD risk factors to assess which PA
      dimensions were associated with the first CVD event and whether subgroup
      differences exist. METHODS: A total of 1449 individuals [median age 65.8 (IQR:
      61.2, 70.7) years] with low to high risk of type 2 diabetes and free from CVD
      from the Danish ADDITION-PRO study were included for survival analysis. PA was
      measured by individually calibrated heart rate and movement sensing for 7
      consecutive days. The associations of different PA dimensions (PA energy
      expenditure, time spent in light-, moderate- and vigorous intensity PA),
      sedentary time and other conventional CVD risk factors with the first CVD event
      were examined by tree-structured survival analysis. Baseline information was
      linked to data on the first CVD event (ischemic heart disease, ischemic stroke,
      heart failure, atrial flutter/fibrillation and atherosclerotic disease) and
      mortality obtained from Danish registers. RESULTS: During a median follow-up time
      of 5.5 (IQR: 5.1-6.1) years, a total of 201 individuals (13.9%) developed CVD.
      Overall CVD incidence rate was 2.6/100 person-years. PA energy expenditure above
      43 kJ/kg/day was associated with lower rates of CVD events among participants <=
      70 years and with HbA1c <= 5.7% (39 mmol/mol), systolic blood pressure <= 156
      mmHg and albumin creatinine ratio <= 70 (incidence rates 0.0-0.8/100 person
      years). CONCLUSIONS: Any type of PA resulting in increased PA energy expenditure
      may over time be the best prevention strategy to uphold reduced risk of CVD.

PMID- 30208899
TI  - Systematic review of health state utility values in metastatic non-small cell
      lung cancer with a focus on previously treated patients.
AB  - BACKGROUND: Health state utility values (HSUVs) are an important input to
      economic evaluations and the choice of HSUV can affect the estimate of relative
      cost-effectiveness between interventions. This systematic review identified
      utility scores for patients with metastatic non-small cell lung cancer (mNSCLC),
      as well as disutilities or utility decrements relevant to the experience of
      patients with mNSCLC, by treatment line and health state. METHODS: The
      MEDLINE(r), Embase and Cochrane Library databases were systematically searched
      (September 2016) for publications describing HSUVs in mNSCLC in any treatment
      line. The EQ-5D website, the School of Health and Related Research Health
      Utilities Database (ScHARRHUD) and major pharmacoeconomic and clinical
      conferences in 2015-2016 were also queried. Studies in adults with previously
      treated mNSCLC were selected for further analysis. The information extracted
      included study design, description of treatment and health state, respondent
      details, instrument and tariff, HSUV or (dis) utility decrement estimates,
      quality of study, and appropriateness for use in economic evaluations. RESULTS:
      Of 1883 references identified, 36 publications of 34 studies were included: 19
      reported EQ-5D scores; eight reported HSUVs from valuations of vignettes made by
      members of the public using standard gamble (SG) or time trade-off (TTO); two
      reported SG or TTO directly elicited from patients; two reported EQ-5D visual
      analogue scale scores only; one reported Assessment of Quality of Life instrument
      scores; one reported HSUVs for caregivers to patients with mNSCLC using the 12
      item Short-Form Health Survey; and one estimated HSUVs based on expert opinion.
      The range of HSUVs identified for comparable health states showed how differences
      in study type, tariff, health state and the measures used can drive variation in
      HSUV estimates. CONCLUSIONS: This systematic review provides a set of published
      HSUVs that are relevant to the experience of adult patients previously treated
      for mNSCLC. Our review begins to address the challenge of identifying reliable
      estimates of utility values in mNSCLC that are suitable for use in economic
      evaluations, and also highlights how varying estimates result from differences in
      methodology.

PMID- 30208901
TI  - Increased serum concentration of ceramides in obese children with nonalcoholic
      fatty liver disease.
AB  - BACKGROUND: Hepatic lipid accumulation is closely related to the development of
      insulin resistance, which is regarded as one of the most significant risk factors
      of nonalcoholic fatty liver disease (NAFLD). Although the exact molecular pathway
      leading to impaired insulin signaling has not been definitively established,
      ceramides are suspected mediators of lipid induced hepatic insulin resistance.
      Therefore, the aim of the study was to evaluate the serum ceramides concentration
      in obese children with NAFLD. METHODS: The prospective study included 80 obese
      children (aged 7-17 years, median 12 years) admitted to our Department to
      diagnose initially suspected liver disease. Patients with viral hepatitis (HCV,
      HBV, CMV), autoimmune (AIH), toxic and metabolic (Wilson's disease, alfa-1
      antitrypsin deficiency) liver diseases and celiac disease were excluded. NAFLD
      was diagnosed based on pediatric diagnostic criteria in obese children with liver
      steatosis in ultrasound (US) as well as elevated alanine transaminase (ALT) serum
      activity after exclusion of other major liver diseases listed before.
      Ultrasonography was used as a screening method and for qualitative assessment of
      the steatosis degree (graded according to Saverymuttu scale). Advanced steatosis
      was defined as a score > 1. The total intrahepatic lipid content (TILC) was
      assessed by magnetic resonance proton spectroscopy (1HMRS) which is the most
      accurate technique for assessment of ectopic fat accumulation. Fasting serum
      concentration of ceramides was measured in 62 children. RESULTS: NAFLD was
      diagnosed in 31 children. Significant, positive correlation was found between
      total serum concentration of ceramides and insulin (r = 0.3, p = 0.02) and HOMA
      IR (r = 0.28, p = 0.03). Total ceramide concentration as well as specific fatty
      acid-ceramides (FA-ceramides) concentrations, namely: myristic, palmitic,
      palmitoleic, stearic, oleic, behenic and lignoceric were significantly higher (p
      = 0.004, p = 0.003, p = 0.007, p < 0.001, p = 0.035, p = 0.008, p = 0.003, p =
      0.006, respectively) in children with NAFLD compared to controls (n = 14).
      Moreover, children with NAFLD had significantly higher activity of ALT (p <
      0.001) and GGT (p < 0.001), HOMA-IR (p = 0.04), BMI (p = 0.046), waist
      circumference (p = 0.01) steatosis grade in ultrasound (p < 0.001) and TILC in
      1HMRS (p < 0.001) compared to children without NAFLD. We did not find significant
      differences in total and FA-ceramide species concentrations between children with
      mild (grade 1) and advanced liver steatosis in ultrasonography (grade 2-3).
      CONCLUSION: Elevated ceramide concentrations in obese patients together with
      their significant correlation with insulin resistance parameters suggest their
      association with molecular pathways involved in insulin signaling impairment
      known to be strongly linked to pathogenesis of non-alcoholic fatty liver disease.

PMID- 30208903
TI  - A huge lacrimal gland ductule dacryolith with a hairy nucleus: a case report.
AB  - BACKGROUND: Dacryoliths in lacrimal gland ductule are a rare condition and an
      unusual cause of conjunctivitis. Here we report a case with a large lacrimal
      gland ductule stone with an unique hairy nucleus. CASE PRESENTATION: A 38-year
      old female presented with a red left eye for one month. Physical examination
      revealed an inflammatory granuloma in the lateral canthus and a fistula with
      purulent secretion. Antibiotics did not ameliorate the symptoms. After we incised
      the fistula, a huge dacryolith (10 mm * 5 mm * 3 mm) was identified at the end of
      the dilated lacrimal gland ductule and was removed surgically. Histopathologic
      examination showed a hairy nucleus surrounded by lamellar structure. The symptoms
      were resolved in 2 weeks after dacryolith extraction. The formation of the hair
      centered dacryolith might be associated with the patient's personal history of
      being a rabbit raiser for years. CONCLUSION: We should be aware of lacrimal gland
      ductule dacryolith as a rare cause of conjunctivitis. The relationship between
      dacryolithiasis and fur-bearing animal raising warrants further investigation.

PMID- 30208904
TI  - Introducing novel and comprehensive models for predicting recurrence in breast
      cancer using the group LASSO approach: are estimates of early and late recurrence
      different?
AB  - BACKGROUND: In here, we constructed personalized models for predicting breast
      cancer (BC) recurrence according to timing of recurrence (as early and late
      recurrence). METHODS: An efficient algorithm called group LASSO was used for
      simultaneous variable selection and risk factor prediction in a logistic
      regression model. RESULTS: For recurrence < 5 years, age (OR 0.96, 95% CI = 0.95
      0.97), number of pregnancies (OR 0.94, 95% CI = 0.89-0.99), family history of
      other cancers (OR 0.73, 95% CI = 0.60-0.89), hormone therapy (OR 0.76, 95% CI =
      0.61-0.96), dissected lymph nodes (OR 0.98, 95% CI = 0.97-0.99), right-sided BC
      (OR 0.87, 95% CI = 0.77-0.99), diabetes (OR 0.77, 95% CI = 0.60-0.98), history of
      breast operations (OR 0.38, 95% CI = 0.17-0.88), smoking (OR 5.72, 95% CI = 2.11
      15.55), history of breast disease (OR 3.32, 95% CI = 1.92-5.76), in situ
      component (OR 1.58, 95% CI = 1.35-1.84), tumor necrosis (OR 1.87, 95% CI = 1.57
      2.22), sentinel lymph node biopsy (SLNB) (OR 2.90, 95% CI = 2.05-4.11) and
      SLNB+axillary node dissection (OR 3.50, 95% CI = 2.26-5.42), grade 3 (OR 1.79,
      95% CI = 1.46-2.21), stage 2 (OR 2.71, 95% CI = 2.18-3.35), stages 3 and 4 (OR
      5.01, 95% CI = 3.52-7.13), and mastectomy+radiotherapy (OR 2.97, 95% CI = 2.39
      3.68) were predictors of recurrence < 5 years. Moreover, relative to mastectomy
      without radiotherapy (as reference for comparison), quadrantectomy without
      radiotherapy had a noticeably higher odds ratio compared to quadranectomy with
      radiotherapy for recurrence < 5 years. (OR 17.58, 95% CI = 6.70-46.10 vs. OR:
      2.50, 95% CI = 2-3.12). Accuracy, sensitivity, and specificity of the model were
      82%, 75.6%, and 74.9%, respectively. For recurrence > 5 years, stage 2 cancer (OR
      1.67, 95% CI = 1.31-2.14) and radiotherapy+mastectomy (OR 2.45, 95% CI = 1.81
      3.32) were significant predictors; furthermore, relative to mastectomy without
      radiotherapy (as reference for comparison), quadranectomy without radiotherapy
      had a noticeably higher odds ratio compared to quadranectomy with radiotherapy
      for recurrence > 5 years (OR 7.62, 95% CI = 1.52-38.15 vs. OR 1.75, 95% CI = 1.32
      2.32). Accuracy, sensitivity, and specificity of the model were 71%, 78.8%, and
      55.8%, respectively. CONCLUSION: For the first time, we constructed models for
      estimating recurrence based on timing of recurrence which are among the most
      applicable models with excellent accuracy (> 80%).

PMID- 30208902
TI  - Exploring the vagueness of Religion & Spirituality in complex pediatric decision
      making: a qualitative study.
AB  - BACKGROUND: Medical advances have led to new challenges in decision-making for
      parents of seriously ill children. Many parents say religion and spirituality
      (R&S) influence their decisions, but the mechanism and outcomes of this influence
      are unknown. Health care providers (HCPs) often feel unprepared to discuss R&S
      with parents or address conflicts between R&S beliefs and clinical
      recommendations. Our study sought to illuminate the influence of R&S on parental
      decision-making and explore how HCPs interact with parents for whom R&S are
      important. METHODS: A longitudinal, qualitative, descriptive design was used to
      (1) identify R&S factors affecting parental decision-making, (2) observe changes
      in R&S themes over time, and (3) learn about HCP perspectives on parental R&S.
      The study sample included 16 cases featuring children with complex life
      threatening conditions. The length of study for each case varied, ranging in
      duration from 8 to 531 days (median = 380, mean = 324, SD = 174). Data from each
      case included medical records and sets of interviews conducted at least monthly
      with mothers (n = 16), fathers (n = 12), and HCPs (n = 108). Thematic analysis
      was performed on 363 narrative interviews to identify R&S themes and content
      related to decision-making. RESULTS: Parents from 13 cases reported R&S directly
      influenced decision-making. Most HCPs were unaware of this influence. Fifteen R&S
      themes appeared in parent and HCP transcripts. Themes most often associated with
      decision-making were Hope & Faith, God is in Control, Miracles, and Prayer.
      Despite instability in the child's condition, these themes remained consistently
      relevant across the trajectory of illness. R&S influenced decisions about
      treatment initiation, procedures, and life-sustaining therapy, but the variance
      in effect of R&S on parents' choices ultimately depended upon other medical & non
      medical factors. CONCLUSIONS: Parents consider R&S fundamental to decision
      making, but apply R&S concepts in vague ways, suggesting R&S impact how decisions
      are made more than what decisions are made. Lack of clarity in parental
      expressions of R&S does not necessarily indicate insincerity or underestimation
      of the seriousness of the child's prognosis; R&S can be applied to decision
      making in both functional and dysfunctional ways. We present three models of how
      religious and spiritual vagueness functions in parental decision-making and
      suggest clinical applications.

PMID- 30208905
TI  - Trauma and perceived social rejection among Yazidi women and girls who survived
      enslavement and genocide.
AB  - BACKGROUND: In August 2014, the Islamic State of Iraq and Syria (ISIS), a
      terrorist organization, attacked the Yazidi's ancestral homeland in northwestern
      Iraq. Among other atrocities, they abducted thousands of women and girls and
      traded many of them into sexual slavery. The aim of this study is to determine
      the mental health of women and girl survivors of these events in relation to
      enslavement and experiences with genocide-related events, as well as perceived
      social rejection in their community. METHODS: Between February and July 2017,
      trained local assessors interviewed a sample of 416 Yazidi women and girls (65 of
      whom had survived sexual enslavement), aged between 17 and 75 years, and living
      in internally displaced person camps in the Kurdistan Region of Iraq. Post
      traumatic stress disorder (PTSD) and depression symptoms were assessed using
      validated Kurdish versions of standard instruments. Scales for trauma exposure
      and perceived rejection were developed for the purpose of this study. RESULTS:
      Participants reported a high number of traumatic events. More than 80% of girls
      and women, and almost all participants who were formerly enslaved, met criteria
      for a probable DSM-5 PTSD diagnosis. Trauma exposure and enslavement predicted
      poor mental health. In addition, among formerly enslaved girls and women,
      perceived social rejection in their community mediated the relationship between
      traumatic enslavement events and depression symptoms. CONCLUSIONS: In a context
      of maximum adversity, enslavement and war-related events contribute to high
      levels of PTSD and depression. Perceived social rejection seems to play a role in
      the relationship between trauma exposure and mental health among abducted
      genocide survivors. Providing psychosocial support and treatment for Yazidi
      people is essential and urgently required.

PMID- 30208906
TI  - "Babies born early?" - silences about prematurity and their consequences.
AB  - BACKGROUND: The principal aim of this study was to understand how communication
      between parents and health professionals concerning prematurity occurs, from
      delivery to admission to the neonatal Intensive Care Unit. METHODS: This is an
      exploratory, descriptive study with a qualitative methodology. Data were
      collected using tape-recorded and Focal Groups technique interview with mothers
      of premature newborns and health professionals involved in caring for preterm
      infants, at southeast Brazil. RESULTS: The word "premature" was not said or heard
      during prenatal care. From the narratives, it was observed that there was a lack
      of information available to pregnant women about preterm birth, failure in
      medical care regarding signs and symptoms reported by pregnant women, and lack of
      communication between the medical teams, mothers and family during delivery and
      Neonatal Intensive Care Unit (NICU) admission. CONCLUSION: There is a fine line
      between born too soon and die too soon, that increases stress, fear and distance
      impacting negatively over communication between mothers and health professionals
      during antenatal care, childbirth and NICU admission.

PMID- 30208907
TI  - Retraction Note: Downregulated poly-C binding protein-1 is a novel predictor
      associated with poor prognosis in acute myeloid leukemia.
AB  - This article [1] is retracted at request of the Editor.

PMID- 30208909
TI  - Overweight, obesity, and food consumption in Galapagos, Ecuador: a window on the
      world.
AB  - BACKGROUND: In order to understand why rates of overweight and obesity are so
      high in the Ecuadorian province of Galapagos, this study analyzes changes in
      household food expenditures and perceptions and practices related to food
      consumption patterns. Galapagos is understood as an unusual but not unique case
      because conditions there graphically illustrate trends observed in communities
      and countries worldwide. A mixed methods approach was employed: a quantitative
      component was based on expenditures for foods classified according to the NOVA
      system, and a qualitative component utilized focus group discussions, key
      informant interviews, and structured observations. RESULTS: Galapagos residents
      increased consumption of processed and ultra-processed foods and decreased
      consumption of unprocessed and minimally processed foods. Perceived barriers to
      healthy diets include price, availability, and quality of fresh produce, as well
      as easy access to industrialized processed and ultra-processed foods.
      CONCLUSIONS: Changes in consumption patterns represent both local conditions and
      global trends; in that sense, the factors that affect Galapagos residents are not
      unique. Hence, these findings help elucidate processes observed in communities
      around the world.

PMID- 30208908
TI  - Assessment of acute, 14-day, and 13-week repeated oral dose toxicity of Tiglium
      seed extract in rats.
AB  - BACKGROUND: Seed of mature Croton tiglium Linne, also known as Tiglium seed (TS),
      has been widely used as a natural product due to its several health beneficial
      properties including anti-tumor and antifungal activities. Despite its
      ethnomedicinal beneficial properties, toxicological information regarding TS
      extract, especially its long-term toxicity, is currently limited. Therefore, the
      objective of the present study was to evaluate acute and subchronic toxicity of
      TS extract in rats after oral administration following test guidelines of the
      Organization for Economic Cooperation and Development (OECD). METHODS:
      Toxicological properties of TS extract were evaluated by toxicity assays to
      determine its single-dose acute toxicity (125, 250, 500, 1000, or 2000 mg/kg), 14
      day repeated-dose toxicity (125, 250, 500, 1000, or 2000 mg/kg) and 13-week
      repeated-dose toxicity (31.25, 62.5, 125, 250, and 500 mg/kg) in Sprague-Dawley
      rats and F344 rats. Hematological, serum biochemical, and histopathological
      parameters were analyzed to determine its median lethal dose (LD50) and no
      observed-adverse-effect-level (NOAEL). RESULTS: Oral single dose up to 2000 mg/kg
      of TS extract resulted in no mortalities or abnormal clinical signs. In 13-week
      toxicity study, TS extract exhibited no dose-related changes (mortality, body
      weight, food/water consumption, hematology, clinical biochemistry, organ weight,
      or histopathology) at dose up to 500 mg/kg, the highest dosage level suggested
      based on 14-day repeat-dose oral toxicity study. CONCLUSION: Acute oral LD50 of
      TS extract in rats was estimated to be greater than 2000 mg/kg. NOAEL of TS
      extract administered orally was determined to be 500 mg/kg/day in both male and
      female rats. Results from these acute and subchronic toxicity assessments of TS
      extract under Good Laboratory Practice regulations indicate that TS extract
      appears to be safe for human consumption.

PMID- 30208910
TI  - Bone shape mediates the relationship between sex and incident knee
      osteoarthritis.
AB  - BACKGROUND: Knee bone shape differs between men and women and the incidence of
      knee osteoarthritis (OA) is higher in women than in men. Therefore, the purpose
      of the present study was to determine whether the observed difference in the
      incidence of knee radiographic OA (ROA) between men and women is mediated by bone
      shape. METHODS: We randomly sampled 304 knees from the OAI with incident ROA
      (i.e., development of Kellgren/Lawrence grade >= 2 by month 48) and 304 knees
      without incident ROA. We characterized distal femur and proximal tibia shape on
      baseline radiographs using Statistical Shape Modeling. If a specific bone shape
      was associated with the risk of incident ROA, marginal structural models were
      generated to assess the mediation effect of that bone shape on the relation of
      sex and risk of incident knee ROA adjusting for baseline covariates. RESULTS:
      Case and control participants were similar by age, sex and race, but case knees
      were from higher body mass index (BMI) participants (29.4 vs. 27.0; p < 0.001).
      Women had 49% increased odds of incident knee ROA compared with men (adjusted
      odds ratio (OR) = 1.49, 95% Confidence Interval (C.I.): 1.04, 2.12). There was an
      inconsistent mediation effect for tibial mode 2 between sex and incident knee
      ROA, with an indirect effect OR of 0.96 (95% C.I.: 0.91-1.00) and a direct effect
      OR of 1.56 (95% C.I.: 1.08-2.27), suggesting a protective effect for this mode.
      Similar findings were also observed for the mediation effect of tibia mode 10 and
      femur mode 4. These shape modes primarily involved differences in the angular
      relation of the heads to the shafts of the femur and tibia. CONCLUSIONS: Distal
      femur and proximal tibia bone shapes partially and inconsistently mediated the
      relationship between sex and incident knee OA. Women had a higher risk of
      incident ROA, and specific bone shapes modestly protected them from even higher
      risk of ROA. The clinical significance of these findings warrant further
      investigation.

PMID- 30208912
TI  - Impairment of respiratory muscle strength in Berardinelli-Seip congenital
      lipodystrophy subjects.
AB  - BACKGROUND: Berardinelli-Seip Congenital Generalized Lipodystrophy (BSCL) is an
      ultra-rare metabolic disease characterized by hypertriglyceridemia,
      hyperinsulinemia, hyperglycemia, hypoleptinemia, and diabetes mellitus. Although
      cardiovascular disturbances have been observed in BSCL patients, there are no
      studies regarding the Respiratory Muscle Strength (RMS) in this type of
      lipodystrophy. This study aimed to evaluate RMS in BSCL subjects compared with
      healthy subjects. METHODS: Eleven individuals with BSCL and 11 healthy subjects
      matched for age and gender were included in this study. The Maximum Inspiratory
      Pressure (MIP), Maximum Expiratory Pressure (MEP), and Peripheral Muscle Strength
      (PMS) were measured for three consecutive years. BSCL subjects were compared to
      healthy individuals for MIP, MEP, and PMS. Correlations between PMS and MIP were
      also analyzed. The genetic diagnosis was performed, and sociodemographic and
      anthropometric data were also collected. RESULTS: BSCL subjects showed
      significantly lower values for MIP and MEP (p <  0.0001 and p = 0.0002,
      respectively) in comparison to healthy subjects, but no changes in handgrip
      strength (p = 0.15). Additionally, we did not observe changes in MIP, MEP, and
      PMS two years after the first analysis, showing maintenance of respiratory
      dysfunction in BSCL subjects (p = 0.05; p = 0.45; p = 0.99). PMS and MIP were not
      correlated in these subjects (r = 0.56; p = 0.18). CONCLUSION: BSCL subjects
      showed lower respiratory muscle strength when compared with healthy subjects;
      however, PMS was not altered. These findings were maintained at similar levels
      during the two years of evaluation. Our data reveal the first association of BSCL
      with the development of respiratory muscle weakness.

PMID- 30208911
TI  - Sex-specific associations between telomere length and candidate miRNA expression
      in placenta.
AB  - BACKGROUND: In the early-life environment, proper development of the placenta is
      essential for both fetal and maternal health. Telomere length at birth has been
      related to life expectancy. MicroRNAs (miRNAs) as potential epigenetic
      determinants of telomere length at birth have not been identified. In this study,
      we investigate whether placental miRNA expression is associated with placental
      telomere length at birth. METHODS: We measured the expression of seven candidate
      miRNAs (miR-16-5p, -20a-5p, -21-5p, -34a-5p, 146a-5p, -210-3p and -222-3p) in
      placental tissue at birth in 203 mother-newborn (51.7% girls) pairs from the
      ENVIRONAGE birth cohort. We selected miRNAs known to be involved in crucial
      cellular processes such as inflammation, oxidative stress, cellular senescence
      related to aging. Placental miRNA expression and relative average placental
      telomere length were measured using RT-qPCR. RESULTS: Both before and after
      adjustment for potential covariates including newborn's ethnicity, gestational
      age, paternal age, maternal smoking status, maternal educational status, parity,
      date of delivery and outdoor temperature during the 3rd trimester of pregnancy,
      placental miR-34a, miR-146a, miR-210 and miR-222 expression were significantly (p
      <= 0.03) and positively associated with placental relative telomere length in
      newborn girls. In newborn boys, only higher expression of placental miR-21 was
      weakly (p = 0.08) associated with shorter placental telomere length. Significant
      miRNAs explain around 6-8% of the telomere length variance at birth. CONCLUSIONS:
      Placental miR-21, miR-34a, miR-146a, miR-210 and miR-222 exhibit sex-specific
      associations with telomere length in placenta. Our results indicate miRNA
      expression in placental tissue could be an important determinant in the process
      of aging starting from early life onwards.

PMID- 30208914
TI  - Single fraction of accelerated partial breast irradiation in the elderly: early
      clinical outcome.
AB  - BACKGROUND: To analyze the clinical outcome of elderly women with early breast
      cancer who underwent accelerated partial breast irradiation (APBI) based on a
      post-operative single fraction of multicatheter interstitial high dose-rate
      brachytherapy (MIB). METHODS: A single institution retrospective cohort study was
      performed focusing on elderly patients (>= 65 years old) presenting a low-risk
      breast carcinoma treated by lumpectomy plus axillary evaluation followed by MIB.
      A single fraction of 16 Gy was prescribed on the 100% isodose. Clinical outcome
      at 3 years was reported based on local relapse free survival (3-y LRFS), specific
      survival (SS) and overall survival (OS). Acute (< 180 days after APBI) and late
      toxicity were evaluated. Cosmetic results were clinically evaluated by the
      physician. RESULTS: Between January 2012 and August 2015, 48 women (51 lesions)
      were treated. Median age was 77.7 years (range: 65-92) with a median tumor size
      of 12 mm (range: 3-32). Five patients (pts) presented an axillary lymph node
      involvement (4 Nmic, 1 N1). Invasive ductal carcinoma was the most frequent
      histology type (86.3%). With a median follow-up of 40 months (range: 36-42), no
      local relapse occurred while 1 pt. developed axillary relapse (2.1%). The 3-y
      LRFS, SS and OS rates were 100%, 100% and 93.1% respectively. Forty-five acute
      events were remained. The most frequent acute toxicity was grade (G) 1
      hyperpigmentation (26.7%), 3 pts. (6.3%) presented G3 acute toxicity (2 breast
      hematomas, 1 breast abscess). No >= G3 late toxicity was observed while 15 late
      toxicities occurred (G1: 13 events - 86.7%) mainly breast fibrosis). The rate of
      excellent cosmetic outcome was 76.4%. CONCLUSION: We reported promising and
      encouraging clinical outcome of a post-operative single fraction of MIB ABPI in
      the elderly. This approach leads to consider a sfAPBI as an attractive
      alternative to intra-operative radiation therapy while all the patients will be
      good candidates for APBI in regards to the post-operative pathological report.
      More mature results (number of patients and follow-up) are needed.

PMID- 30208913
TI  - Client and provider factors associated with integration of family planning
      services among maternal and reproductive health clients in Kigoma Region,
      Tanzania: a cross-sectional study, April-July 2016.
AB  - BACKGROUND: Integration of family planning (FP) services into non-FP care visits
      is an essential strategy for reducing maternal and neonatal mortality through
      reduction of short birth intervals and unplanned pregnancies. METHODS: Cross
      sectional surveys were conducted across 61 facilities in Kigoma Region, Tanzania,
      April-July 2016. Multilevel, mixed effects logistic regression analyses were
      conducted on matched data from providers (n = 330) and clients seeking delivery
      (n = 935), well-baby (n = 272), pregnancy loss (PL; n = 229), and other routine
      (postnatal, HIV/STI, other; n = 69) services. Outcomes of interest included
      receipt of FP information and a modern FP method (significance level p < 0.05).
      RESULTS: Clients had significantly greater odds of receiving FP information if
      the primary reason for seeking care was for PL versus (vs) any other types of
      care (aOR 1.97), had four or more pregnancies vs fewer (aOR 1.78), and had had a
      FP discussion with their partner vs no FP discussion (aOR 1.73). Clients had
      lower odds of receiving FP information if they were aged 40-49 vs 15-19 (aOR
      0.50) and reported attending religious services at least weekly vs less
      frequently (aOR 0.61). Clients of providers who perceived that in-service
      training had helped vs had not helped job performance (aOR 2.27), and clients of
      providers having high vs low recent FP training index scores (aOR 1.58) had
      greater odds of receiving FP information. Clients had greater odds of receiving a
      modern method when they received information on two or more vs fewer methods (aOR
      7.13), had had a FP discussion with their partner vs no discussion (aOR 5.87), if
      the primary reason for seeking care was for PL vs any other types of care (aOR
      4.08), had zero vs one or more live births (aOR 3.92), made their own FP
      decisions vs not made own FP decisions (aOR 3.17), received FP information from
      two or more vs fewer sources (aOR 3.12), and were in the middle or high vs the
      low wealth tercile (aOR 1.99 and 2.30, respectively). Well-baby care clients,
      Other routine services clients, and married clients had significantly lower odds
      of receiving a method (aOR 0.14; aOR 0.08; and aOR 0.41, respectively) compared
      to their counterparts. CONCLUSIONS: Strategies that better integrate FP into
      routine care visits, encourage women to have FP discussions with their partners
      and providers, increase FP training among providers, and expand FP options and
      sources of information may help reduce the unmet need for FP, and ultimately
      lower maternal and neonatal mortality.

PMID- 30208915
TI  - A continuous repetitive task to detect fatigability in spinal muscular atrophy.
AB  - BACKGROUND: To determine the value of a continuous repetitive task to detect and
      quantify fatigability as additional dimension of impaired motor function in
      patients with hereditary proximal spinal muscular atrophy (SMA). RESULTS: In this
      repeated measure case-control study 52 patients with SMA types 2-4, 17 healthy
      and 29 disease controls performed five consecutive rounds of the Nine-Hole Peg
      test to determine the presence of fatigability. We analysed differences in test
      performance and associations with disease characteristics. Five patients with SMA
      type 2 (22%) and 1 disease control (3%) could not finish five rounds due to
      fatigue (p = 0.01). Patients with SMA type 2 performed the test significantly
      more slowly than all other groups (p < 0.005) and disease controls were slower
      than healthy controls (p < 0.05). Patients with SMA type 2 performed round five
      27% slower than round one, while healthy controls performed round five 14% faster
      than round one (p = 0.005). There was no difference between SMA type 3a, type
      3b/4 or disease controls and healthy controls (p > 0.4). Time needed to complete
      each round during the five-round task increased in 15 patients with SMA type 2
      (65%), 4 with type 3a (36%), 4 with type 3b/4 (22%), 9 disease controls (31%) and
      1 healthy control (6%). There was no effect of age at disease onset or disease
      duration in SMA type 2 (p = 0.39). Test-retest reliability was high. CONCLUSION:
      Fatigability of remaining arm function is a feature of SMA type 2 and can be
      determined with continuous repetitive tasks.

PMID- 30208916
TI  - The "hot potato" topic: challenges and facilitators to promoting respectful
      maternal care within a broader health intervention in Tanzania.
AB  - In recent years, mistreatment during childbirth has captured the public health
      and maternal health consciousness as not only an affront to women's rights but
      also a formidable deterrent to the uptake of facility-based childbirth - and thus
      to reductions in maternal mortality. The challenge ahead is to determine what can
      be done to address this public health problem. A modest but growing body of
      research has demonstrated that interventions to foster Respectful Maternity Care
      (RMC) can enact change, albeit in the relatively controlled context of a trial or
      study. Herein we describe our experiences in weaving elements of RMC across tiers
      of an existing maternal and newborn health program. As a commentary, this
      document does not outline program results, but instead highlights challenges and
      facilitators to promoting RMC within a large-scale, multi-district health
      platform. We conclude with lessons learned during the process and urge that
      others share their program learning experiences in an effort to strengthen the
      knowledge base on what works and what does not work in terms of addressing this
      complex, context-sensitive issue.

PMID- 30208918
TI  - Time-course mass spectrometry data of adipose mesenchymal stem cells acquiring
      chondrogenic phenotype.
AB  - OBJECTIVES: Rabbit adipose mesenchymal stem cells were used for the purpose of
      studying acquisition of the chondrogenic phenotype over time at 1, 14 and 28 days
      after in vitro incubation with differentiation media, using nano-liquid
      chromatography electrospray ionization tandem mass spectrometry analysis. This
      was part of a preliminary study of the behavior of differentiated adipose stem
      cells for use in a rabbit model of laryngoplasty. DATA DESCRIPTION: The data
      comprise .MGF, .RAW, .MZID, and .XLSX, lists of peaks, peptides and proteins
      identified by nano-flow liquid chromatography electrospray ionization tandem mass
      spectrometry analysis upon incubation with non-differentiating (ND) or
      chondrogenic differentiating (CHD) media (ProteomeXchange ID PXD010236). XLSX
      files contain the following information: day 1 CT (control, N = 3499 proteins),
      day 14 ND (N = 3106 proteins), day 28 ND (N = 3116 proteins), day 14 CHD (N =
      2901 proteins), and day 28 CHD (N = 2876 proteins). Proteins are characterized
      with respect to their - 10lgP value, percent coverage, number of total as well as
      unique peptides after trypsin digestion, derivatization method
      (carbamidomethylation, oxidation, or combined carbamidomethylation + oxidation),
      average mass, and include a full description.

PMID- 30208917
TI  - Mucosal associated invariant T cells from human breast ducts mediate a Th17
      skewed response to bacterially exposed breast carcinoma cells.
AB  - BACKGROUND: Antimicrobial T cells play key roles in the disease progression of
      cancers arising in mucosal epithelial tissues, such as the colon. However, little
      is known about microbe-reactive T cells within human breast ducts and whether
      these impact breast carcinogenesis. METHODS: Epithelial ducts were isolated from
      primary human breast tissue samples, and the associated T lymphocytes were
      characterized using flow cytometric analysis. Functional assays were performed to
      determine T-cell cytokine secretion in response to bacterially treated human
      breast carcinoma cells. RESULTS: We show that human breast epithelial ducts
      contain mucosal associated invariant T (MAIT) cells, an innate T-cell population
      that recognizes specific bacterial metabolites presented by nonclassical MR1
      antigen-presenting molecules. The MAIT cell population from breast ducts
      resembled that of peripheral blood in its innate lymphocyte phenotype (i.e.,
      CD161, PLZF, and interleukin [IL]-18 receptor coexpression), but the breast duct
      MAIT cell population had a distinct T-cell receptor Vbeta use profile and was
      markedly enriched for IL-17-producing cells compared with blood MAIT cells.
      Breast carcinoma cells that had been exposed to Escherichia coli activated MAIT
      cells in an MR1-dependent manner. However, whereas phorbol 12-myristate 13
      acetate/ionomycin stimulation induced the production of both interferon-gamma and
      IL-17 by breast duct MAIT cells, bacterially exposed breast carcinoma cells
      elicited a strongly IL-17-biased response. Breast carcinoma cells also showed
      upregulated expression of natural killer group 2 member D (NKG2D) ligands
      compared with primary breast epithelial cells, and the NKG2D receptor contributed
      to MAIT cell activation by the carcinoma cells. CONCLUSIONS: These results
      demonstrate that MAIT cells from human breast ducts mediate a selective T-helper
      17 cell response to human breast carcinoma cells that were exposed to E. coli.
      Thus, cues from the breast microbiome and the expression of stress-associated
      ligands by neoplastic breast duct epithelial cells may shape MAIT cell responses
      during breast carcinogenesis.

PMID- 30208919
TI  - Association between SMAD3 gene polymorphisms and osteoarthritis risk: a
      systematic review and meta-analysis.
AB  - OBJECTIVE: Several studies have been performed to investigate the association
      between SMAD3 gene polymorphism and osteoarthritis (OA), but the results were
      inconclusive. This study aims to determine whether SMAD3 polymorphism is
      associated with risk of OA. METHOD: A comprehensive literature search in PubMed,
      Embase, and ISI Web of Science for relevant studies was performed. After
      extracting data from eligible studies, we chose the fixed or random effect model
      according to the heterogeneity test. Estimation of publication bias and
      sensitivity analysis were conducted to confirm the stability of this meta
      analysis. RESULTS: In total, 10 studies from 6 articles with 5093 OA patients and
      5699 controls were enrolled in this meta-analysis. The combined results revealed
      significant association between SMAD3 rs12901499 polymorphism and the risk of OA
      (allele model: OR 1.21, 95% CI 1.07-1.38). Subgroup analysis revealed that G
      allele increased the risk of OA in Caucasians, but not in Asians (allele model:
      Caucasians: OR 1.31, 95% CI 1.18-1.44; Asians: OR 1.24, 95% CI 0.95-1.61). And
      the pooled results revealed significant association between SMAD3 rs12901499
      polymorphism and both knee and hip OA (knee OA: OR 1.18, 95% CI 1.04-1.34; hip
      OA: OR 1.31, 95% CI 1.18-1.44). CONCLUSION: The current meta-analysis revealed
      that the G variant of SMAD3 rs12901499 polymorphism increased the risk of OA in
      Caucasians. Further well-designed studies with larger sample size in different
      ethnic populations are required to confirm these results.

PMID- 30208920
TI  - Remnant preservation technique versus standard technique for anterior cruciate
      ligament reconstruction: a meta-analysis of randomized controlled trials.
AB  - BACKGROUND: This meta-analysis was performed to compare the clinical outcomes of
      primary anterior cruciate ligament (ACL) reconstruction using the ACL remnant
      preservation technique versus the standard technique. METHODS: PubMed, Embase,
      and the Cochrane Library were searched through December 24, 2017, to identify
      randomized controlled studies that compared the use of the ACL remnant
      preservation technique versus the standard technique for primary ACL
      reconstruction. Statistical heterogeneity among the trials was evaluated with chi
      square and I-square tests. A sensitivity analysis was conducted to explore
      sources of heterogeneity. Subgroup analysis was performed to identify potential
      differences according to type of ACL remnant tissue (remnant bundle or remnant
      fibers). RESULTS: Seven studies with a combined 412 patients (208 in the remnant
      preservation technique group and 204 in the standard technique group) were
      included in the meta-analysis. There was a significant difference between the
      groups in Lysholm score (mean difference (MD), 2.20; 95% confidence interval
      (CI), 0.95-3.45; P = 0.0006) and side-to-side difference (MD, - 0.71; 95% CI, -
      0.87 to - 0.55; P < 0.01). There was no significant difference between the groups
      in subjective International Knee Documentation Committee (IKDC) score,
      complications, pivot shift test, Lachman test, or overall IKDC score. Subgroup
      analysis demonstrated that for primary ACL reconstruction with preservation of
      remnant fibers, the remnant preservation technique was superior to the standard
      technique based on Lysholm scores (P < 0.01) and side-to-side difference (P <
      0.01). CONCLUSIONS: Based on the current literature, using the remnant
      preservation technique showed a better clinical outcome than using the standard
      technique for patients undergoing primary ACL reconstruction with respect to
      Lysholm score and side-to-side difference. However, it remains unclear that there
      is a definite advantage to use the remnant preservation technique compared with
      the standard technique.

PMID- 30208922
TI  - Retraction Note: HMGB1: a novel protein that induced platelets active and
      aggregation via Toll-like receptor-4, NF-kappaB and cGMP dependent mechanisms.
AB  - This article [1] is retracted at request of the Editor.

PMID- 30208921
TI  - An evaluation of health systems equity in Indonesia: study protocol.
AB  - BACKGROUND: Many low and middle income countries are implementing reforms to
      support Universal Health Coverage (UHC). Perhaps one of the most ambitious
      examples of this is Indonesia's national health scheme known as the JKN which is
      designed to make health care available to its entire population of 255 million by
      end of 2019. If successful, the JKN will be the biggest single payer system in
      the world. While Indonesia has made steady progress, around a third of its
      population remains without cover and out of pocket payments for health are
      widespread even among JKN members. To help close these gaps, especially among the
      poor, the Indonesian government is currently implementing a set of UHC policy
      reforms that include the integration of remaining government insurance schemes
      into the JKN, expansion of provider networks, restructuring of provider payments
      systems, accreditation of all contracted health facilities and a range of demand
      side initiatives to increase insurance uptake, especially in the informal sector.
      This study evaluates the equity impact of this latest set of UHC reforms.
      METHODS: Using a before and after design, we will evaluate the combined effects
      of the national UHC reforms at baseline (early 2018) and target of JKN full
      implementation (end 2019) on: progressivity of the health care financing system;
      pro-poorness of the health care delivery system; levels of catastrophic and
      impoverishing health expenditure; and self-reported health outcomes. In-depth
      interviews with stakeholders to document the context and the process of
      implementing these reforms, will also be undertaken. DISCUSSION: As countries
      like Indonesia focus on increasing coverage, it is critically important to ensure
      that the poor and vulnerable - who are often the most difficult to reach - are
      not excluded. The results of this study will not only help track Indonesia's
      progress to universalism but also reveal what the UHC-reforms mean to the poor.

PMID- 30208923
TI  - Determination of the expression of three fimbrial subunit proteins in cultured
      Trueperella pyogenes.
AB  - BACKGROUND: Trueperella pyogenes is a commensal and a significant opportunistic
      pathogen in animals. A variety of identified or putative virulence factors are
      considered to significantly contribute to the occurrence of T. pyogenes infection
      in different species. However, these virulence factors are not fully understood.
      RESULTS: In the current study, the genes encoding putative fimbrial proteins,
      i.e. Fim A, Fim C, and Fim E, were cloned. Recombinant Fim A (rFim A), Fim C
      (rFim C), and Fim E (rFim E) were prepared and used to generate rabbit anti-rFim
      A, anti-rFim C, and anti-rFim E serum, respectively. Using these sera, we found
      that only Fim E was constitutively expressed in T. pyogenes. The expression level
      of Fim E in T. pyogenes peaked within 6-10 h of culture period in pH 7.5. Fim E
      protein expression was unaffected by anaerobic condition, but was inhibited by
      the microaerophilic condition. Tube agglutination tests indicated that Fim E was
      exhibited on the surface of T. pyogenes cells because anti-rFim E serum caused
      strong agglutination. Additionally, the blots for Fim A detection showed
      nonspecific reactions. Furthermore, the tube agglutination tests showed that anti
      Fim A serum failed to cause agglutination of T. pyogenes cells, which indicated
      that Fim A was not, or poorly, expressed in cultured T. pyogenes. Anti-rFim C
      serum caused strong agglutination. However, the blots for Fim C detection showed
      a strong nonspecific reaction. Thus, the expression of Fim C was difficult to be
      determined using the current method. CONCLUSIONS: Fim E was expressed in cultured
      T. pyogenes. However, Fim A was either not or poorly expressed in cultured T.
      pyogenes. Moreover, Fim C expression was not determined using the current
      strategy.

PMID- 30208924
TI  - LGR5, a novel functional glioma stem cell marker, promotes EMT by activating the
      Wnt/beta-catenin pathway and predicts poor survival of glioma patients.
AB  - BACKGROUND: Tumor recurrence, the chief reason for poor prognosis of glioma, is
      largely attributed to glioma stem cells (GSCs) and epithelial-mesenchymal
      transition (EMT). However, the mechanisms among them remain unknown. Here, we
      determined whether leucine-rich repeat-containing G protein-coupled receptor 5
      (LGR5), known as a stem cell marker for colon cancer and gastric cancer, can
      serve as a novel GSC marker involved in EMT and a therapeutic target in glioma.
      METHODS: Stemness properties were examined in FACS-isolated LGR5+/LGR5- cells.
      Reported stem cell markers, EMT and the Wnt/beta-catenin pathway were examined in
      stable LGR5 knockdown or overexpressed GSCs by Western Blot. The treatment
      experiment was performed in an intracranial orthotopic xenograft model by
      knockdown of LGR5 or by using the Wnt/beta-catenin pathway inhibitor Wnt-C59.
      LGR5 expression was determined in 268 glioma specimens by immunohistochemistry.
      RESULTS: LGR5+ cells possessed stronger stemness properties compared to LGR5-
      cells. The expression of SOX2, Nanog, CD133, CD44, CD24 and EpCAM was modulated
      by LGR5. Both LGR5 knockdown and Wnt-C59 reduced tumor invasion and migration and
      blocked EMT by inhibiting the Wnt/beta-catenin pathway in vitro and suppressed
      the intracranial orthotopic xenograft growth and prolonged the survival of
      xenograft mice in vivo. Moreover, LGR5 was positively correlated with Ki67, N
      cadherin and WHO grade and negatively correlated with IDH1. Glioma patients with
      high expression of LGR5 showed significantly poorer prognosis. CONCLUSIONS: LGR5
      is a new functional GSC marker and prognostic indicator that can promote EMT by
      activating the Wnt/beta-catenin pathway and would thus be a novel therapeutic
      target for glioma.

PMID- 30208925
TI  - Vitamin D and the promoter methylation of its metabolic pathway genes in
      association with the risk and prognosis of tuberculosis.
AB  - BACKGROUND: A variety of abnormalities in vitamin D metabolism have been reported
      in patients with active tuberculosis. However, intervention trials have produced
      inconsistent results. We hypothesized that genetic and epigenetic changes in the
      key genes of the vitamin D metabolic pathway may partly explain the differences
      between studies. METHODS: We performed a case-control study followed by a
      prospective cohort study. We recruited 122 patients with pulmonary tuberculosis
      and 118 healthy controls. The serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin
      D levels were measured. The methylation of the promoter regions of key genes in
      the vitamin D metabolic pathway (CYP24A1, CYP27A1, CYP27B1, CYP2R1, and VDR) was
      detected using the Illumina MiSeq platform. The specific methylation profiles
      were examined as epigenetic biomarkers. The sensitivity, specificity, and
      receiver operating characteristic (ROC) curves were used to estimate the
      predictive value of the biomarkers. RESULTS: The baseline serum 25-hydroxyvitamin
      D and 1,25-dihydroxyvitamin D concentrations in the cases were significantly
      lower than those in the controls (51.60 +/- 27.25 nmol/L vs. 117.50 +/- 75.50
      nmol/L, Z = - 8.515, P < 0.001; 82.63 +/- 51.43 pmol/L vs. 94.02 +/- 49.26
      pmol/L, Z = - 2.165, P = 0.03). We sequenced 310 CpG sites in five candidate
      genes. After Bonferroni correction, there were 55 differentially methylated CpG
      sites between cases and controls; 41.5% were in the CYP27B1 gene, 31.7% were in
      the CYP24A1 gene, 14.7% were in the VDR gene, and 12.3% were in the CYP27A1 gene.
      When we designated the CpG sites that remained significant after the Bonferroni
      correction as the biomarkers, the area under the curve (AUC) for the cumulative
      methylation was 0.810 (95% CI 0.754-0.866). There was an interaction between
      CYP27A1 methylation level and 1,25-dihydroxyvitamin D concentration associated
      with the risk of TB (ORinteraction = 4.11, 95% CI 1.26-13.36, P = 0.019). The
      serum 1,25-dihydroxyvitamin D concentration at the end of the intensive treatment
      stage was related to a patient's prognosis (P = 0.008). There were 23 CpG sites
      that were individually related to the treatment outcomes, but the relationships
      were not significant after the Bonferroni correction. CONCLUSION: Both serum
      vitamin D concentrations and the methylation levels of key genes in the vitamin D
      metabolic pathway are related to the risk and prognosis of tuberculosis.

PMID- 30208926
TI  - Environmental enrichment reduces adolescent anxiety- and depression-like
      behaviors of rats subjected to infant nerve injury.
AB  - BACKGROUND: Infant nerve injury causes delayed adolescent neuropathic pain, but
      whether it also leads to psychiatric illness is unknown. Environmental enrichment
      (EE) increases social communication and activity. Thus, our goal was to test
      anxiety- and depression-like behaviors after infant peripheral nerve injury and
      evaluate the effect of environmental enrichment on these models of affective
      disorders. METHODS: Open field, elevated plus maze, sucrose preference, and pain
      behaviors (paw withdrawal threshold, spontaneous guarding score, and cold
      response to acetone) were measured in rats that received infant spared nerve
      injury (SNI). Enzyme-linked immune absorbent assay of cytokines was performed to
      evaluate the inflammatory response in the brain. Then, the ability of
      intracerebroventricular (ICV) injection of a microglia inhibitor, minocycline
      (MIN), and EE (a free-running wheel, a staircase, a plastic tunnel, a raised
      platform, and various colored balls) to reverse the infant SNI effects on
      behaviors and cytokines was examined. RESULTS: Infant nerve injury resulted in
      adolescent anxiety- and depression-like behaviors. The medial prefrontal cortex,
      basolateral amygdala, and ventral hippocampus were skewed to a pro-inflammatory
      profile. ICV injection of MIN reduced anxiety- and depression-like behaviors
      without affecting pain behaviors. In addition, ICV MIN skewed the brain towards
      an anti-inflammatory profile. Finally, environmental enrichment improved anxiety-
      and depression-like behaviors, as well as pain behaviors. EE increased brain IL
      10 and decreased IL-1beta and TNF-alpha. CONCLUSIONS: Infant nerve injury induces
      adolescent anxiety- and depression-like behaviors and central nervous
      inflammation. Environmental enrichment reduces these behaviors by normalizing the
      inflammation balance in the brain.

PMID- 30208927
TI  - Combined detection of COMP and CS846 biomarkers in experimental rat
      osteoarthritis: a potential approach for assessment and diagnosis of
      osteoarthritis.
AB  - BACKGROUND: To comprehensively evaluate the diagnostic value of serum cartilage
      oligomeric matrix protein (COMP) and chondroitin sulfate 846 epitope (CS846)
      biomarkers in osteoarthritis (OA), longitudinal and combined measurement of serum
      COMP and CS846 were performed at different stages in the pathological process of
      OA in a rat model of anterior cruciate ligament transection (ACLT). METHODS:
      Sixty male Sprague-Dawley rats were randomly divided into two groups, including a
      model group (n = 30) and a control group (n = 30). Rat models were established by
      ACLT surgery, and sham operations were performed on rats in the control group.
      Prior to surgery and at 2, 4, 6, 8, and 10 weeks after ACLT surgery, serum levels
      of COMP and CS846 biomarkers were determined using an enzyme-linked immunosorbent
      assay approach. Five rats per group were euthanized at 2, 4, 6, 8, and 10 weeks
      after surgery, after which tibial plateau specimens were collected. Macroscopic
      observation and histological examination were employed for rat tibial plateau.
      Histological changes in articular cartilage were evaluated according to
      Osteoarthritis Research Society International (OARSI) scoring criteria. The area
      under the curve (AUC) of COMP, CS846, and combined biomarkers was compared using
      receiver operating characteristic (ROC) curve. RESULTS: Within 10 weeks after
      surgery, serum levels of COMP and CS846 in the model group were significantly
      higher when compared to those in the control group. Moreover, a significant
      correlation was observed between changes in COMP and CS846 levels. At each time
      point, macroscopic observations and OARSI scores were significantly increased in
      the development of OA. The AUC of combined biomarkers was higher compared to that
      of COMP and CS846 alone. Finally, a positive relationship was found between
      levels of COMP and CS846 and the OARSI score. CONCLUSIONS: In this study, we
      found that combined detection of serum CS846 and COMP levels can be used for
      diagnosis and monitoring of OA progression.

PMID- 30208928
TI  - Sex-specific differences in organic anion transporting polypeptide 1a4 (Oatp1a4)
      functional expression at the blood-brain barrier in Sprague-Dawley rats.
AB  - BACKGROUND: Targeting endogenous blood-brain barrier (BBB) transporters such as
      organic anion transporting polypeptide 1a4 (Oatp1a4) can facilitate drug delivery
      for treatment of neurological diseases. Advancement of Oatp targeting for
      optimization of CNS drug delivery requires characterization of sex-specific
      differences in BBB expression and/or activity of this transporter. METHODS: In
      this study, we investigated sex differences in Oatp1a4 functional expression at
      the BBB in adult and prepubertal (i.e., 6-week-old) Sprague-Dawley rats. We also
      performed castration or ovariectomy surgeries to assess the role of gonadal
      hormones on Oatp1a4 protein expression and transport activity at the BBB. Slco1a4
      (i.e., the gene encoding Oatp1a4) mRNA expression and Oatp1a4 protein expression
      in brain microvessels was determined using quantitative real-time PCR and western
      blot analysis, respectively. Oatp transport function at the BBB was determined
      via in situ brain perfusion using [3H]taurocholate and [3H]atorvastatin as probe
      substrates. Data were expressed as mean +/- SD and analyzed via one-way ANOVA
      followed by the post hoc Bonferroni t-test. RESULTS: Our results showed increased
      brain microvascular Slco1a4 mRNA and Oatp1a4 protein expression as well as
      increased brain uptake of [3H]taurocholate and [3H]atorvastatin in female rats as
      compared to males. Oatp1a4 expression at the BBB was enhanced in castrated male
      animals but was not affected by ovariectomy in female animals. In prepubertal
      rats, no sex-specific differences in brain microvascular Oatp1a4 expression were
      observed. Brain accumulation of [3H]taurocholate in male rats was increased
      following castration as compared to controls. In contrast, there was no
      difference in [3H]taurocholate brain uptake between ovariectomized and control
      female rats. CONCLUSIONS: These novel data confirm sex-specific differences in
      BBB Oatp1a4 functional expression, findings that have profound implications for
      treatment of CNS diseases. Studies are ongoing to fully characterize molecular
      pathways that regulate sex differences in Oatp1a4 expression and activity.

PMID- 30208929
TI  - PLD3 epigenetic changes in the hippocampus of Alzheimer's disease.
AB  - BACKGROUND: Whole-exome sequencing has revealed a rare missense variant in PLD3
      gene (rs145999145) to be associated with late onset Alzheimer's disease (AD).
      Nevertheless, the association remains controversial and little is known about the
      role of PLD3 in AD. Interestingly, PLD3 encodes a phospholipase that may be
      involved in amyloid precursor protein (APP) processing. Our aim was to gain
      insight into the epigenetic mechanisms regulating PLD3 gene expression in the
      human hippocampus affected by AD. RESULTS: We assessed PLD3 mRNA expression by
      qPCR and protein levels by Western blot in frozen hippocampal samples from a
      cohort of neuropathologically confirmed pure AD cases and controls. Next, we
      profiled DNA methylation at cytosine-phosphate-guanine dinucleotide (CpG) site
      resolution by pyrosequencing and further validated results by bisulfite cloning
      sequencing in two promoter regions of the PLD3 gene. A 1.67-fold decrease in PLD3
      mRNA levels (p value < 0.001) was observed in the hippocampus of AD cases
      compared to controls, and a slight decrease was also found by Western blot at
      protein level. Moreover, PLD3 mRNA levels inversely correlated with the average
      area of beta-amyloid burden (tau-b = - 0,331; p value < 0.01) in the hippocampus.
      A differentially methylated region was identified within the alternative promoter
      of PLD3 gene showing higher DNA methylation levels in the AD hippocampus compared
      to controls (21.7 +/- 4.7% vs. 18.3 +/- 4.8%; p value < 0.05). CONCLUSIONS: PLD3
      gene is downregulated in the human hippocampus in AD cases compared to controls.
      Altered epigenetic mechanisms, such as differential DNA methylation within an
      alternative promoter of PLD3 gene, may be involved in the pathological processes
      of AD. Moreover, PLD3 mRNA expression inversely correlates with hippocampal beta
      amyloid burden, which adds evidence to the hypothesis that PLD3 protein may
      contribute to AD development by modifying APP processing.

PMID- 30208930
TI  - Transient severe distributive shock due to early dumping syndrome: a case report.
AB  - BACKGROUND: Early dumping syndrome characterized by palpitation, dizziness, cold
      sweat, feebleness, and abdominal symptoms, occurs within 30 minutes after meals
      in patients who have undergone gastrectomy. This case report describes the case
      of a patient who presented with severe distributive shock due to early dumping
      syndrome; he recovered within a few hours after massive fluid infusion and
      vasopressor administration. CASE PRESENTATION: Our patient was a 68-year-old
      Japanese man who underwent total gastrectomy for gastric cancer and was diagnosed
      as having late dumping syndrome. On admission, he developed severe shock and was
      treated with massive fluid administration. Based on the history of the present
      illness, past medical history, normal findings of blood chemistry test, transient
      course, and Sigtad score, which helps diagnose dumping syndrome, early dumping
      syndrome was considered the cause of severe distributive shock. CONCLUSIONS:
      Early dumping syndrome can cause severe shock requiring massive fluid infusion
      and vasopressor administration. It should be considered a cause of severe
      distributive shock in patients who have undergone gastrectomy.

PMID- 30208931
TI  - HDAC4 in ischemic stroke: mechanisms and therapeutic potential.
AB  - Stroke is one of the leading causes of death and disability worldwide, and the
      majority of the cases are ischemic stroke. However, it still lacks effective
      treatment except for thrombolytic therapy in an extremely narrow time window.
      Increased evidence suggests that histone deacetylase 4 (HDAC4) was dysregulated
      in ischemic stroke, which plays a key role in the pathogenesis of ischemic stroke
      and post-stroke recovery by affecting neuronal death, angiogenesis, and
      neurogenesis. Therefore, we aim to review the dysregulation of HDAC4 in ischemic
      stroke and the role of dysregulated HDAC4 in the pathogenesis of ischemic stroke.
      Furthermore, the therapeutic potential of modulating HDAC4 in ischemic stroke is
      discussed.

PMID- 30208933
TI  - Stabilizing HIV-1 envelope glycoprotein trimers to induce neutralizing
      antibodies.
AB  - An effective HIV-1 vaccine probably will need to be able to induce broadly
      neutralizing HIV-1 antibodies (bNAbs) in order to be efficacious. The many bNAbs
      that have been isolated from HIV-1 infected patients illustrate that the human
      immune system is able to elicit this type of antibodies. The elucidation of the
      structure of the HIV-1 envelope glycoprotein (Env) trimer has further fueled the
      search for Env immunogens that induce bNAbs, but while native Env trimer mimetics
      are often capable of inducing strain-specific neutralizing antibodies (NAbs)
      against the parental virus, they have not yet induced potent bNAb responses. To
      improve the performance of Env trimer immunogens, researchers have studied the
      immune responses that Env trimers have induced in animals; they have evaluated
      how to best use Env trimers in various immunization regimens; and they have
      engineered increasingly stabilized Env trimer variants. Here, we review the
      different approaches that have been used to increase the stability of HIV-1 Env
      trimer immunogens with the aim of improving the induction of NAbs. In particular,
      we draw parallels between the various approaches to stabilize Env trimers and
      ones that have been used by nature in extremophile microorganisms in order to
      survive in extreme environmental conditions.

PMID- 30208932
TI  - Nogo-B receptor increases the resistance to tamoxifen in estrogen receptor
      positive breast cancer cells.
AB  - BACKGROUNDS: Tamoxifen is typically used to treat patients with estrogen receptor
      alpha (ERalpha)-positive breast cancer. However, 30% of these patients gain
      acquired resistance to tamoxifen during or after tamoxifen treatment. As a Ras
      modulator, Nogo-B receptor (NgBR) is required for tumorigenesis through the
      signaling crosstalk with epidermal growth factor (EGF) receptor (EGFR)-mediated
      pathways. NgBR is highly expressed in many types of cancer cells and regulates
      the sensitivity of hepatocellular carcinoma to chemotherapy. In this study, we
      found the expression of NgBR is increased in tamoxifen-resistant ERalpha-positive
      breast cancer cells. METHODS: Tamoxifen-resistant ERalpha-positive MCF-7 and T47D
      breast cancer cell lines were established by culturing with gradually increased
      concentration of 4-hydroxytamoxifen (4-OHT). The effects of NgBR on tamoxifen
      resistance was determined by depleting NgBR in these cell lines using previously
      validated small interfering RNA (siRNA). The effects of 4-OHT on cell viability
      and apoptosis were determined using well-accepted methods such as clonogenic
      survival assay and Annexin V/propidium iodide staining. The alteration of EGF
      stimulated signaling and gene expression was determined by western blot analysis
      and real-time PCR, respectively. RESULTS: NgBR knockdown with siRNA attenuates
      EGF-induced phosphorylation of ERalpha and restores the sensitivity to tamoxifen
      in ERalpha-positive breast cancer cells. Mechanistically, our data demonstrated
      that NgBR knockdown increases the protein levels of p53 and decreases survivin,
      which is an apoptosis inhibitor. CONCLUSIONS: These results suggested that NgBR
      is a potential therapeutic target for increasing the sensitivity of ERalpha
      positive breast cancer to tamoxifen.

PMID- 30208935
TI  - Retraction Note: Protective role of silymarin in a mouse model of renal Ischemia
      Reperfusion injury.
AB  - This article [1] is retracted at request of the Editor. After publication of this
      article [1] concerns were raised regarding aspects of the methodology, including
      the choice of stains being inappropriate or inadequate to answer the research
      question. A discrepancy was also noted between the number of groups described in
      the methods and the number of groups presented in some of the figures.
      Furthermore the western blot images did not entirely correspond with the
      information reported in the results. For these reasons the conclusions of the
      study cannot be considered to be supported by the data. All authors agree to this
      retraction.

PMID- 30208934
TI  - Emerging themes in food security: environmental justice, extended families and
      the multiple roles of grandmothers.
AB  - BACKGROUND: Pre- and perinatal nutritional status defines the development of
      adult metabolism and energy balance in humans. Young children in poor households
      are disproportionately more vulnerable to food insecurity given the cumulative
      impact of chronic stress on susceptibility to chronic diseases as an adult.
      Qualitative studies focusing on the experience of food insecurity in Latin
      America are scarce. In Argentina, although socioeconomic indicators improved in
      the aftermath of the 2001ecomomic crisis, the disadvantaged provinces in the
      north continue to bear the burden of historical inequities. The study was
      conducted among Primary Health Care patients in the city of San Salvador de
      Jujuy, Argentina. It analyzes environmental and household level stressors through
      the narratives of mothers with young children living with food insecurity, from
      the perspectives of eco-developmental conceptual frameworks. METHODS: We
      conducted 11 semi-structured interviews with mothers of children < 1 to 6 years
      of age who participated in maternal-child health programs in Primary Health Care
      clinics and lived in food insecure households. Interviews focused on the
      environmental context and the resources and processes for obtaining and preparing
      daily meals. RESULTS: The Eco-bio-developmental (EBD) framework and the
      vulnerability-assets approach, provided a basis for conceptualizing the
      significance of findings. Our results indicated the need to understand pathways
      in the association of stressors, vulnerability and ill health, as well as the
      mitigating role of social relationships. For example, understanding the link
      between the stress of being exposed to environmental contaminants and the
      capacity to overcome food insecurity, or developing strategies to integrate the
      support provided by kinship networks like extended families into food security
      programs. The results also indicate the importance of developing support
      mechanisms for vulnerable family members like grandmothers in food insecure
      households who play instrumental roles as providers and caretakers of younger
      relatives. CONCLUSION: The empirical evidence generated by this study may inform
      community based strategies and public health policies to address food insecurity
      in vulnerable population groups who face health effects from multiple stressors.

PMID- 30208936
TI  - Abdominal organ position variation in children during image-guided radiotherapy.
AB  - BACKGROUND: Interfractional organ position variation might differ for abdominal
      organs and this could have consequences for defining safety margins. Therefore,
      the purpose of this study is to quantify interfractional position variations of
      abdominal organs in children in order to investigate possible correlations
      between abdominal organs and determine whether position variation is location
      dependent. METHODS: For 20 children (2.2-17.8 years), we retrospectively analyzed
      113 CBCTs acquired during the treatment course, which were registered to the
      reference CT to assess interfractional position variation of the liver, spleen,
      kidneys, and both diaphragm domes. Organ position variation was assessed in three
      orthogonal directions and relative to the bony anatomy. Diaphragm dome position
      variation was assessed in the cranial-caudal (CC) direction only. We investigated
      possible correlations between position variations of the organs (Spearman's
      correlation test, rho), and tested if organ position variations in the CC
      direction are related to the diaphragm dome position variations (linear
      regression analysis, R2) (both tests: significance level p < 0.05). Differences
      of variations of systematic (?) and random errors (sigma) between organs were
      tested (Bonferroni significance level p < 0.004). RESULTS: In all directions,
      correlations between liver and spleen position variations, and between right and
      left kidney position variations were weak (rho <= 0.43). In the CC direction, the
      position variations of the right and left diaphragm domes were significantly, and
      stronger, correlated with position variations of the liver (R2 = 0.55) and spleen
      (R2 = 0.63), respectively, compared to the right (R2 = 0.00) and left kidney (R2
      = 0.25). Differences in ? and sigma between all organs were small and
      insignificant. CONCLUSIONS: No (strong) correlations between interfractional
      position variations of abdominal organs in children were observed. From present
      results, we concluded that diaphragm dome position variations could be more
      representative for superiorly located abdominal (liver, spleen) organ position
      variations than for inferiorly located (kidneys) organ position variations.
      Differences of systematic and random errors between abdominal organs were small,
      suggesting that for margin definitions, there was insufficient evidence of a
      dependence of organ position variation on anatomical location.

PMID- 30208937
TI  - Small-scale field testing of alpha-cypermethrin water-dispersible granules in
      comparison with the recommended wettable powder formulation for indoor residual
      spraying against malaria vectors in Benin.
AB  - BACKGROUND: Pyrethroids are the most common class of insecticide used worldwide
      for indoor residual spraying (IRS) against malaria vectors. Water-dispersible
      granules (WG) are a pyrethroid formulation to be applied after disintegration and
      dispersion in water with less risks of inhalation than using the usual wettable
      powder (WP) formulation. The objective of this small-scale field study was to
      evaluate efficacy and duration of insecticidal action of a new alpha-cypermethrin
      WG (250 g a.i./kg) against susceptible Anopheles gambiae in comparison with the
      WHO reference product (alpha-cypermethrin WP, 50 g a.i./kg) on the most common
      indoor surfaces in Benin. METHODS: Both formulations were applied at two target
      dose concentrations in houses made of mud and cement in the Tokoli village in
      southern Benin. We measured the applied dose of insecticide by chemical analysis
      of filter paper samples collected from the sprayed inner walls. We recorded An.
      gambiae mortality and knock-down rates every 15 days during 6 months using
      standard WHO bioassays. RESULTS: The alpha-cypermethrin WG formulation did not
      last as long as the WP formulation on both surfaces. The difference is higher
      with the 30 mg/m2 concentration for which the WP formulation reached the 80%
      mortality threshold during 2 months on the mud-plastered walls (3 months on
      cement) whereas the WG formulation last only one month (2 months on cement).
      CONCLUSIONS: The new WG formulation has a shorter efficacy than the WHO
      recommended WP formulation. In this trial, both the WG and WP formulations had
      low durations of efficacy that would need at least two rounds of spray to cover
      the entire transmission season.

PMID- 30208939
TI  - The effect of intensive exercise program and kinesiotaping following total knee
      arthroplasty on functional recovery of patients.
AB  - BACKGROUND: Total knee arthroplasty (TKA) is a gold standard for terminal term
      gonarthrosis patients in order to diminish pain, correct deformities, and regain
      stability. Postoperative functional recovery of patients depends on the current
      postoperative rehabilitation program to an important extent. The purpose of our
      study is to compare midterm functional level of gonarthrosis patients who were
      included in physiotherapy rehabilitation program following TKA with people in
      similar ages without any surgical indication nor intervention. We have aimed also
      to compare functionality of people who had additional kinesiotaping (KT)
      treatment with people who had conservative treatment only after knee
      arthroplasty. METHODS: Functional level and knee functionality of people in study
      were evaluated at the end of postoperative first month by 6-min walk test and
      Lysholm knee score respectively. RESULTS: There was no statistical difference
      between groups with and without TKA in terms of height, weight, body mass index,
      Lysholm score, and 6-min walk test score (p > 0.05). In patient group with TKA,
      people with postoperative KT treatment had greater 6-min walk test score for
      postoperative first month (p = 0.005). CONCLUSION: TKA is considered a gold
      standard procedure in order to increase the quality of life and improve
      functionality of terminal term gonarthrosis patients. It is necessary to
      immediately control pain and edema of knee and apply intensive rehabilitation
      program aimed at muscle strengthening around hip and knee in order to increase
      the success of operation.

PMID- 30208938
TI  - Potential adverse effects of botanical supplementation in high-fat-fed female
      mice.
AB  - BACKGROUND: Insulin resistance underlies metabolic syndrome and is associated
      with excess adiposity and visceral fat accumulation, which is more frequently
      observed in males than females. However, in young females, the prevalence of
      metabolic syndrome is rising, mainly driven by accumulation of abdominal visceral
      fat. The degree to which sex-related differences could influence the development
      of insulin resistance remains unclear, and studies of potential therapeutic
      strategies to combat metabolic syndrome using rodent models have focused
      predominantly on males. We therefore evaluated the effects of two nutritional
      supplements derived from botanical sources, an extract of Artemisia dracunculus
      L. (termed PMI5011) and Momordica charantia (commonly known as bitter melon), on
      female mice challenged with a high-fat diet in order to determine if dietary
      intake of these supplements could ameliorate obesity-induced insulin resistance
      and metabolic inflexibility in skeletal muscle. METHODS: Body composition,
      physical activity and energy expenditure, fatty acid oxidation, insulin
      signaling, and gene and protein expression of factors controlling lipid
      metabolism and ectopic lipid accumulation were evaluated in female mice fed a
      high-fat diet supplemented with either PMI5011 or bitter melon. Statistical
      significance was assessed by unpaired two-tailed t test and repeated measures
      ANOVA. RESULTS: PMI5011 supplementation resulted in increased body weight and
      adiposity, while bitter melon did not induce changes in these parameters.
      Pyruvate tolerance testing indicated that both supplements increased hepatic
      glucose production. Both supplements induced a significant suppression in fatty
      acid oxidation in skeletal muscle homogenates treated with pyruvate, indicating
      enhanced metabolic flexibility. PMI5011 reduced lipid accumulation in skeletal
      muscle, while bitter melon induced a downward trend in lipid accumulation in the
      skeletal muscle and liver. This was accompanied by transcriptional regulation of
      autophagic genes by bitter melon in the liver. CONCLUSIONS: Data from the current
      study indicates that dietary supplementation with PMI5011 and bitter melon evokes
      a divergent, and generally less favorable, set of metabolic responses in female
      mice compared to effects previously observed in males. Our findings underscore
      the importance of considering sex-related variations in responses to dietary
      supplementation aimed at combating metabolic syndrome.

PMID- 30208940
TI  - Increased circulating endothelial progenitor cells and improved short-term
      outcomes in acute non-cardioembolic stroke after hyperbaric oxygen therapy.
AB  - BACKGROUND: Acute ischemic stroke is a leading cause of mortality and long-term
      disability, and profiles of endothelial progenitor cells (EPCs) reflect the
      degree of endothelial impairment. This study tested the hypothesis that
      hyperbaric oxygen therapy (HBOT) both improves the clinical short-term outcomes
      and increases the number of circulating EPCs and antioxidant capacity. METHODS:
      The numbers of circulating EPCs [CD133+/CD34+ (%), KDR+/CD34+ (%)], biomarkers
      for oxidative stress (thiols and thiobarbituric acid-reactive substances), and
      clinical scores (National Institutes of Health Stroke Scale [NIHSS], Barthel
      index [BI], and modified Rankin Scale [MRS]) were prospectively evaluated in 25
      patients with acute non-cardioembolic stroke under HBOT at two time points (pre-
      and post-HBOT). The biomarkers and clinical scores were compared with those of 25
      age- and sex-matched disease controls. RESULTS: The numbers of KDR+/CD34+ (%) in
      the HBOT group following HBOT increased significantly, whereas the numbers of
      CD133+/CD34+ (%) also showed a tendency to increase without statistical
      significance. The mean high-sensitivity C-reactive protein levels showed
      significant decrease post-HBOT follow-up in the HBOT group. The changes in
      KDR+/CD34+EPC (%) numbers were positively correlated with changes in clinical
      outcomes scores (BI, NIHSS, and MRS) in the HBOT group. CONCLUSIONS: Based on the
      results of our study, HBOT can both improve short-term clinical outcomes and
      increase the number of circulating EPCs in patients with acute non-cardioembolic
      stroke.

PMID- 30208941
TI  - Molecular surveillance and phylogenetic traits of Babesia bigemina and Babesia
      bovis in cattle (Bos taurus) and water buffaloes (Bubalus bubalis) from Colombia.
AB  - BACKGROUND: Babesia bigemina and B. bovis are two economically important
      hemoparasites affecting both cattle and buffaloes involved in dairy and beef
      production. In Colombia, although some parasitological and serological studies
      suggest an endemicity of these pathogens in areas under 1000 m, little is known
      about its molecular prevalence in different host. The objective of this study was
      to estimate the prevalence and molecular traits of these parasites in cattle and
      buffaloes from two Colombian regions. METHODS: Between 2014 and 2016, a three
      point longitudinal survey was designed in farms from Caribbean and Orinoquia
      regions to evaluate the molecular prevalence of B. bigemina and B. bovis using a
      nested PCR (n-PCR) targeting hypothetical protein (hyp) and rhoptry-associated
      protein (RAP-1) genes, respectively. A total of 1432 cattle, 152 buffalo and 1439
      Rhipicephalus microplus samples were analyzed. Moreover, phylogenetic
      relationship of isolates was analyzed using the 18S rRNA gene. RESULTS: A
      molecular prevalence of 31.6% (24.2% for B. bigemina and 14.4% for B. bovis),
      23.6% (6.5% for B. bigemina and 17.7% for B. bovis) and 4.3% (3.5% for B.
      bigemina and 1.0% for B. bovis) was observed in cattle, buffaloes and
      Rhipicephalus microplus, respectively. Higher values of infection were observed
      during the wet season and late wet season; nevertheless, other variables such as
      age, production type, sex, breed and babesiosis control were also significantly
      associated with infection. Prevalence analysis showed that B. bovis infection was
      higher in cattle that coexist with buffaloes, when compared to those which did
      not. For each species, phylogenetic analyses revealed a high genetic diversity of
      isolates without clusters related to the isolation source. CONCLUSIONS: To our
      knowledge, this is the first longitudinal survey that evaluates through molecular
      methods, the infection of B. bigemina and B. bovis in two important livestock
      regions from Colombia. This study reveals that the prevalence of infection by
      Babesia spp., in cattle and buffaloes are modulated by seasonal variations, host
      factors and vector traits. Our results provide new insights on the
      epidemiological aspects of infection of Babesia spp., in cattle and buffaloes,
      which must be taken into consideration when babesiosis control programs are
      implemented in the study area.

PMID- 30208942
TI  - Modifiable and emerging risk factors for type 2 diabetes in Africa: a systematic
      review and meta-analysis protocol.
AB  - BACKGROUND: Type 2 diabetes mellitus (T2DM) remains a public health problem in
      low-income countries, including African countries. Risk factors of this disease
      in Africa are still unclear. This study will examine the modifiable and emerging
      risk factors associated with T2DM in Africa. METHODOLOGY: The study will include
      a systematic review and meta-analysis of published and unpublished empirical
      studies, reporting quantitative data only. We will conduct a search on scientific
      databases (e.g. Global Health), general online search engines (e.g. Google
      Scholar) and key websites for grey literature using a combination of key
      countries/geographic terms, risk factors (e.g. overweight/obesity) and T2DM
      (including a manual search of the included reference lists). We will use the
      Comprehensive Meta-Analysis Software (CMA) version 2.0 for data management and
      analysis. This protocol follows the Preferred Reporting Items for Systematic
      Review and Meta-Analysis Protocols (PRISMA-P). DISCUSSION: The systematic review
      and meta-analysis will provide a robust and reliable evidence base for policy
      makers and future research. This may help with identifying and implementing more
      cost-effective diabetes prevention strategies and improved resource allocation.
      SYSTEMATIC REVIEW REGISTRATION: This protocol has been registered with the
      PROSPERO international prospective register of systematic reviews. The reference
      number is CRD42016043027 .

PMID- 30208943
TI  - Local angiotensin II contributes to tumor resistance to checkpoint immunotherapy.
AB  - BACKGROUND: Current checkpoint immunotherapy has shown potential to control
      cancer by restoring or activating the immune system. Nevertheless, multiple
      mechanisms are involved in immunotherapy resistance which limits the clinical
      benefit of checkpoint inhibitors. An immunosuppressive microenvironment is an
      important factor mediating the original resistance of tumors to immunotherapy. A
      previous report by our group has demonstrated that local angiotensin II (AngII)
      predominantly exists in a tumor hypoxic microenvironment where hypoxic tumour
      cells produced AngII by a hypoxia-lactate-chymase-dependent mechanism. RESULTS:
      Here, using 4T1 and CT26 syngeneic mouse tumor models, we found that local AngII
      in the tumor microenvironment was involved in immune escape of tumour cells and
      an AngII signaling blockage sensitized tumours to checkpoint immunotherapy.
      Furthermore, an AngII signaling blockage reversed the tumor immunosuppressive
      microenvironment, and inhibition of angiotensinogen (AGT, a precursor of AngII)
      expression strongly triggered an immune-activating cytokine profile in hypoxic
      mouse cancer cells. More importantly, AGT silencing combined with a checkpoint
      blockage generated an abscopal effect in resistant tumors. CONCLUSION: Our study
      demonstrated an important role of local AngII in the formation of a tumor
      immunosuppressive microenvironment and its blockage may enhance tumor sensitivity
      to checkpoint immunotherapy. The combination of an AngII signaling blocker and an
      immune-checkpoint blockage could be a promising strategy to improve tumors
      responses to current checkpoint immunotherapy.

PMID- 30208945
TI  - 3D imaging of PSD-95 in the mouse brain using the advanced CUBIC method.
AB  - AIMS: Postsynaptic density - 95 kDa protein (PSD95) is an important molecule on
      the postsynaptic membrane. It interacts with many other proteins and plays a
      pivotal role in learning and memory formation. Its distribution in the brain has
      been studied previously using in situ hybridization as well as
      immunohistochemistry. However, these studies are based on 2 dimensional (2D)
      sections and results are presented with a few sections. The present study aims to
      show PSD-95 distribution in 3 dimensions (3D) without slicing the brain tissue of
      C57BL/6 mice into sections using the advanced CUBIC technique. METHODS:
      Immunofluorescent staining using a PSD-95 antibody was performed on a half of the
      mouse brain after clarifying it using the advanced CUBIC protocol. The brain
      tissue was imaged using a Zeiss Z1 light sheet microscope and 3D reconstruction
      was completed using the Arivis Vision 4 dimensional (4D) software. RESULTS: The
      majority of brain nuclei have similar distribution pattern to what has been
      reported from in situ hybridization and immunohistochemical studies in the mouse.
      The signal can be easily followed in the 3D and their spatial relationship with
      adjacent structures clearly demarcated. In the present study, some fiber bundles
      also showed strong PSD-95 signal, which is different from what was shown in
      previous studies and need to be confirmed in future studies.

PMID- 30208944
TI  - Functional study of CHS gene family members in citrus revealed a novel CHS gene
      affecting the production of flavonoids.
AB  - BACKGROUND: Citrus flavonoids are considered as the important secondary
      metabolites because of their biological and pharmacological activities. Chalcone
      synthase (CHS) is a key enzyme that catalyses the first committed step in the
      flavonoid biosynthetic pathway. CHS genes have been isolated and characterized in
      many plants. Previous studies indicated that CHS is a gene superfamily. In
      citrus, the number of CHS members and their contribution to the production of
      flavonoids remains a mystery. In our previous study, the copies of CitCHS2 gene
      were found in different citrus species and the sequences are highly conserved,
      but the flavonoid content varied significantly among those species. RESULTS: From
      seventy-seven CHS and CHS-like gene sequences, ten CHS members were selected as
      candidates according to the features of their sequences. Among these candidates,
      expression was detected from only three genes. A predicted CHS sequence was
      identified as a novel CHS gene. The structure analysis showed that the gene
      structure of this novel CHS is very similar to other CHS genes. All three CHS
      genes were highly conserved and had a basic structure that included one intron
      and two exons, although they had different expression patterns in different
      tissues and developmental stages. These genes also presented different
      sensitivities to methyl jasmonate (MeJA) treatment. In transgenic plants, the
      expression of CHS genes was significantly correlated with the production of
      flavonoids. The three CHS genes contributed differently to the production of
      flavonoids. CONCLUSION: Our study indicated that CitCHS is a gene superfamily
      including at least three functional members. The expression levels of the CHS
      genes are highly correlated to the biosynthesis of flavonoids. The CHS enzyme is
      dynamically produced from several CHS genes, and the production of total
      flavonoids is regulated by the overall expression of CHS family genes.

PMID- 30208946
TI  - Research ethics consultation: an attempt and 5-year experience in a Japanese
      University Hospital.
AB  - OBJECTIVE: Research ethics consultation is an advisory activity that differs from
      ethics committees, and its role is not yet widely known in Japan. Research ethics
      consultations were started in 2012 by members of the Clinical Trial Center of
      Tokushima University Hospital, a support section for clinical trials. We analyzed
      the research ethics consultation records from Tokushima University Hospital
      during the 5-year period of 2012-2016 to examine the Japanese context of research
      ethics consultation. RESULTS: During the study period, 125 research ethics
      consultations were carried out, 115 (91%) before starting studies. All but one
      request were from investigators at Tokushima University. The main issue was
      compatibility with guidance and regulations (n = 74, 67.2%), such as ethical
      handling of human biological specimens and information utilized in research; only
      6 (4.8%) requests involved research ethics issues that investigators face in
      their research. Therefore, it is necessary to expand the consultation function,
      with a nationwide system of consultant education and data sharing. Moreover,
      standardization of consultation should be considered.

PMID- 30208947
TI  - Alpha-fetoprotein (AFP) as tumor marker in a patient with urothelial cancer with
      exceptional response to anti-PD-1 therapy and an escape lesion mimic.
AB  - The development of a new lesion in a patient with a complete remission to anti-PD
      1 therapy is highly concerning for a drug resistant escape lesion. Here, we
      present a case of a 62-year-old patient with chemotherapy-resistant metastatic
      urothelial cancer who had a complete remission to pembrolizumab. The patient's
      disease burden tracked closely to serum levels of alpha-fetoprotein (AFP)
      expressed by the tumor and served as an accurate tumor marker. Surveillance
      imaging revealed a solitary growing pulmonary nodule mimicking an escape lesion
      in the absence of an increase in AFP levels. Biopsy of this lesion revealed a
      benign intraparenchymal lymph node with no evidence of metastatic carcinoma. This
      case indicates that in some patients, biomarkers aberrantly expressed by their
      tumors, such as AFP in this patient, may be used as a tumor marker for response
      to anti-PD-1 therapy and emphasizes the importance of confirming potential escape
      lesions by pathologic examination.

PMID- 30208948
TI  - Core-rod myopathy due to a novel mutation in BTB/POZ domain of KBTBD13
      manifesting as late onset LGMD.

PMID- 30208950
TI  - Dichotomous development of the gut microbiome in preterm infants.
AB  - BACKGROUND: Preterm infants are at risk of developing intestinal dysbiosis with
      an increased proportion of Gammaproteobacteria. In this study, we sought the
      clinical determinants of the relative abundance of feces-associated
      Gammaproteobacteria in very low birth weight (VLBW) infants. Fecal microbiome was
      characterized at <= 2 weeks and during the 3rd and 4th weeks after birth, by 16S
      rRNA amplicon sequencing. Maternal and infant clinical characteristics were
      extracted from electronic medical records. Data were analyzed by linear mixed
      modeling and linear regression. RESULTS: Clinical data and fecal microbiome
      profiles of 45 VLBW infants (gestational age 27.9 +/- 2.2 weeks; birth weight
      1126 +/- 208 g) were studied. Three stool samples were analyzed for each infant
      at mean postnatal ages of 9.9 +/- 3, 20.7 +/- 4.1, and 29.4 +/- 4.9 days. The
      average relative abundance of Gammaproteobacteria was 42.5% (0-90%) at <= 2
      weeks, 69.7% (29.9-86.9%) in the 3rd, and 75.5% (54.5-86%) in the 4th week (p <
      0.001). Hierarchical and K-means clustering identified two distinct subgroups:
      cluster 1 started with comparatively low abundance that increased with time,
      whereas cluster 2 began with a greater abundance at <= 2 weeks (p < 0.001) that
      decreased over time. Both groups resembled each other by the 3rd week. Single
      variants of Klebsiella and Staphylococcus described variance in community
      structure between clusters and were shared between all infants, suggesting a
      common, hospital-derived source. Fecal Gammaproteobacteria was positively
      associated with vaginal delivery and antenatal steroids. CONCLUSIONS: We detected
      a dichotomy in gut microbiome assembly in preterm infants: some preterm infants
      started with low relative gammaproteobacterial abundance in stool that increased
      as a function of postnatal age, whereas others began with and maintained high
      abundance. Vaginal birth and antenatal steroids were identified as predictors of
      Gammaproteobacteria abundance in the early (<= 2 weeks) and later (3rd and 4th
      weeks) stool samples, respectively. These findings are important in understanding
      the development of the gut microbiome in premature infants.

PMID- 30208949
TI  - The complement system in glioblastoma multiforme.
AB  - The human complement system is represents the main effector arm of innate
      immunity and its ambivalent function in cancer has been subject of ongoing
      dispute. Glioma stem-like cells (GSC) residing in specific niches within
      glioblastomas (GBM) are capable of self-renewal and tumor proliferation. Recent
      data are indicative of the influence of the complement system on the maintenance
      of these cells. It appears that the role of the complement system in glial
      tumorigenesis, particularly its influence on GSC niches and GSC maintenance, is
      significant and warrants further exploration for therapeutic interventions.

PMID- 30208951
TI  - Identification and assessment of virulence of a natural reassortant of infectious
      bursal disease virus.
AB  - Infectious bursal disease virus (IBDV) is one of the most important
      immunosuppressive viral agents in poultry production. Prophylactic vaccinations
      of chicken flocks are the primary tool for disease control. Widely used
      immunoprophylaxis can, however, provide high pressure which contributes to the
      genetic diversification of circulating viruses, e.g. through reassortment of
      genome segments. We report the genetic and phenotypic characterization of a field
      reassortant IBDV (designated as Bpop/03) that acquired segment A from very
      virulent IBDV and segment B from classical attenuated D78-like IBDV. Despite the
      mosaic genetic make-up, the virus caused high mortality (80%) in experimentally
      infected SPF chickens and induced lesions typical of the acute form of IBD. The
      in vivo study results are in contrast with the foregoing experimental
      investigations in which the natural reassortants exhibited an intermediate
      pathotype, and underline the complex nature of IBDV virulence.

PMID- 30208953
TI  - One-minute through test to distinguish lower respiratory infection by analysis of
      sputum; exploring the mechanisms.
AB  - OBJECTIVE: Cough and fever are the initial symptoms of lower respiratory
      infection. Severe cases might be fatal. Therefore, particularly in the non
      equipped centers, the lack of diagnostic methods to identify the severe cases has
      resulted in overconsumption of antibiotics. On the basis of the knowledge about
      non-specific immune response at the site of injury, we developed a colorimetric
      dip-test that shows abrupt, sensitive and quite specific color change upon
      contact with sputum in the cases of lower respiratory infection. We further
      explored the mechanism of the test. RESULTS: We detected deoxyribonucleic acid
      (DNA) and hepatocyte growth factor in the sputum of patients that suffered from
      respiratory infection (n = 18). The results differed significantly (P < 0.0001)
      from age-matched patients (n = 18) with other respiratory disorders and highly
      correlated with the index-test results (Spearman Rank test = 0.84). DNA with a
      concentration more than 0.03 mg/ml induced a visible and stable color change on
      index-test within 1 min. The test recognized all of the cases with respiratory
      infection and the specificity was 72%. With a high negative predictive value. The
      index test detects, inter alia, cell-free DNA in sputum and might safely rule-out
      respiratory infection in 2/3 of cases that present symptoms of acute respiratory
      infection.

PMID- 30208952
TI  - Emerging of antimicrobial resistance in staphylococci isolated from clinical and
      food samples in Algeria.
AB  - OBJECTIVE: The antimicrobial resistance of staphylococci rose worldwide. In
      total, 96 Staphylococcus isolates from food and clinical samples were collected
      from two provinces in Algeria. The antimicrobial susceptibility testing was
      performed and resistance-associated genes were detected. RESULTS: Fifty-one
      strains were isolated from food samples and differentiated into 33 Staphylococcus
      aureus and 18 coagulase-negative staphylococci. Forty-five staphylococci were
      collected from hospital and community-acquired infection cases. All S. aureus
      isolated from food were resistant to penicillin and 45.5% were resistant to
      tetracycline. The resistance rates of 45 clinical Staphylococcus isolates were
      86.7%, 48.9%, 37.8% and 20.0% to penicillin, tetracycline, erythromycin and
      kanamycin, respectively. Nine isolates were confirmed as MRSA from food and
      clinical isolates. One S. aureus originated from food was confirmed as vancomycin
      resistant. Multidrug-resistance was observed among 25.5% and 53.3% of food and
      clinical staphylococci, respectively. The tetM/K, blaZ, aacA-aphD, ermC and mecA
      genes were detected in food and clinical isolates. ermA gene was not found. This
      study provided insight into the status of antimicrobial resistance of
      staphylococci isolated from food and clinical samples in Algeria. Further
      investigations and surveillance programmes are mandatory.

PMID- 30208955
TI  - Some DNM2 mutations cause extremely severe congenital myopathy and phenocopy
      myotubular myopathy.

PMID- 30208954
TI  - Ethical aspects of sudden cardiac arrest research using observational data: a
      narrative review.
AB  - Sudden cardiac arrest (SCA) accounts for half of all cardiac deaths in Europe. In
      recent years, large-scale SCA registries have been set up to enable observational
      studies into risk factors and the effect of treatment approaches. The increasing
      scale and variety of data sources, coupled with the implementation of a new
      European data protection legal framework, causes researchers to struggle with how
      to handle these 'big data'. Data protection in the SCA setting is especially
      complex since patients become at least temporarily incapacitated, and are thus
      unable to provide prospective informed consent, and because the majority of
      patients do not survive. A narrative review employing a systematic literature
      search was conducted to thematically analyse ethical aspects of non
      interventional emergency medicine and critical care research. Although the
      identified issues may apply to a wider patient population, we describe them
      within the context of SCA research. Potential harms were found to include:
      privacy breaches, genetic discrimination and issues associated with the
      disclosure of individual findings, study design and application of research
      results. Measures proposed to mitigate harms were: alternative informed consent
      models including deferred or waived consent and data governance approaches
      promoting data security, responsible sharing and public engagement. The themes
      identified in this study may serve as a basis for a much-needed ethical framework
      regarding research with data from patients with acute and critical illness such
      as SCA.

PMID- 30208956
TI  - Effectiveness of the settings-based intervention Shaping the Social on preventing
      dropout from vocational education: a Danish non-randomized controlled trial.
AB  - BACKGROUND: Lack of formal education is an important social determinant of health
      inequality and represents a public health problem. School dropout is particularly
      common in vocational education; however few prevention programs targeting dropout
      in the vocational school setting have been evaluated. The purpose of the present
      study was to test the effect on school dropout of a settings-based intervention
      program (named Shaping the Social) that targeted the school organization in order
      to create social and supportive learning environments. METHODS: A non-randomized
      controlled design including four large intervention schools and six matched
      control schools was used. The target population was students in technical and
      agricultural vocational education, which is provided to students from age 16.
      Students were enrolled at school start. Register-based data (n = 10,190) was used
      to assess the effect on school dropout during a 2-year period. Odds ratios (OR)
      and 95% confidence intervals (CI) were calculated in logistic regression models,
      adjusting for age, sex, ethnicity, parental income, prior school dropout and type
      of basic course. Student survey (n = 2396) at 10-week follow-up was used to
      examine wellbeing at school (four subscales: school connectedness, student
      support, teacher relatedness, and valuing the profession) which was the
      hypothesized proximal intervention effect. As a secondary aim, we examined how
      the student wellbeing factors were associated with school dropout, independently
      of the intervention, and we explored whether the student wellbeing factors were
      potential mediators. RESULTS: The present study showed an intervention effect on
      school dropout with dropout rates lower in intervention schools (36%) than
      control schools (40%) (OR = 0.86, 95% CI: 0.74, 0.99). We had no attrition on the
      dropout outcome. School connectedness mediated the intervention effect; no
      significant mediation effects were found for student support, teacher
      relatedness, and valuing the profession. Independently of the intervention, each
      student wellbeing factor prevented dropout. CONCLUSIONS: Findings from this study
      suggest that a comprehensive, multicomponent school-based intervention could
      prevent dropout from vocational education by promoting school connectedness;
      nevertheless, the dropout rate remained high. Our results point to the need to
      explore how to further improve the wellbeing at school among young people in
      vocational education. TRIALS REGISTRATION: ISRCTN, ISRCTN57822968 . Registered 16
      January 2013 (retrospective registered).

PMID- 30208957
TI  - Comparative proteomic analysis reveals different responses in porcine lymph nodes
      to virulent and attenuated homologous African swine fever virus strains.
AB  - African swine fever (ASF) is a pathology of pigs against which there is no
      treatment or vaccine. Understanding the equilibrium between innate and adaptive
      protective responses and immune pathology might contribute to the development of
      strategies against ASFV. Here we compare, using a proteomic approach, the course
      of the in vivo infection caused by two homologous strains: the virulent E75 and
      the attenuated E75CV1. Our results show a progressive loss of proteins by day 7
      post-infection (pi) with E75, reflecting tissue destruction. Many signal pathways
      were affected by both infections but in different ways and extensions.
      Cytoskeletal remodelling and clathrin-endocytosis were affected by both isolates,
      while a greater number of proteins involved on inflammatory and immunological
      pathways were altered by E75CV1. 14-3-3 mediated signalling, related to immunity
      and apoptosis, was inhibited by both isolates. The implication of the Rho GTPases
      by E75CV1 throughout infection is also evident. Early events reflected the lack
      of E75 recognition by the immune system, an evasion strategy acquired by the
      virulent strains, and significant changes at 7 days post-infection (dpi),
      coinciding with the peak of infection and the time of death. The protein
      signature at day 31 pi with E75CV1 seems to reflect events observed at 1 dpi,
      including the upregulation of proteosomal subunits and molecules described as
      autoantigens (vimentin, HSPB1, enolase and lymphocyte cytosolic protein 1), which
      allow the speculation that auto-antibodies could contribute to chronic ASFV
      infections. Therefore, the use of proteomics could help understand ASFV
      pathogenesis and immune protection, opening new avenues for future research.

PMID- 30208958
TI  - Modulation of mitochondrial DNA copy number in a model of glioblastoma induces
      changes to DNA methylation and gene expression of the nuclear genome in tumours.
AB  - BACKGROUND: There are multiple copies of mitochondrial DNA (mtDNA) present in
      each cell type, and they are strictly regulated in a cell-specific manner by a
      group of nuclear-encoded mtDNA-specific replication factors. This strict
      regulation of mtDNA copy number is mediated by cell-specific DNA methylation of
      these replication factors. Glioblastoma multiforme, HSR-GBM1, cells are hyper
      methylated and maintain low mtDNA copy number to support their tumorigenic
      status. We have previously shown that when HSR-GBM1 cells with 50% of their
      original mtDNA content were inoculated into mice, tumours grew more aggressively
      than non-depleted cells. However, when the cells possessed only 3% and 0.2% of
      their original mtDNA content, tumour formation was less frequent and the
      initiation of tumorigenesis was significantly delayed. Importantly, the process
      of tumorigenesis was dependent on mtDNA copy number being restored to pre
      depletion levels. RESULTS: By performing whole genome MeDIP-Seq and RNA-Seq on
      tumours generated from cells possessing 100%, 50%, 0.3% and 0.2% of their
      original mtDNA content, we determined that restoration of mtDNA copy number
      caused significant changes to both the nuclear methylome and its transcriptome
      for each tumour type. The affected genes were specifically associated with gene
      networks and pathways involving behaviour, nervous system development, cell
      differentiation and regulation of transcription and cellular processes. The mtDNA
      specific replication factors were also modulated. CONCLUSIONS: Our results
      highlight the bidirectional control of the nuclear and mitochondrial genomes
      through modulation of DNA methylation to control mtDNA copy number, which, in
      turn, modulates nuclear gene expression during tumorigenesis.

PMID- 30208959
TI  - Demographic, clinical, and pathological features of early onset pancreatic cancer
      patients.
AB  - BACKGROUND: Early onset pancreatic cancer (EOPC), i.e. pancreatic ductal
      adenocarcinoma (PDAC) occurring in patients below 50 years of age, is rare and
      there is limited information regarding risk factors, molecular basis and outcome.
      This study aimed to determine the demographic and clinicopathological features
      and survival figures for EOPC. METHODS: A retrospective analysis of patients
      treated at the Royal London Hospital for PDAC between September 2004 and
      September 2015 was performed. Data on demographics, risk factors, presentation,
      pathological features, treatment and survival outcome were compared in EOPC and
      older PDAC patients. RESULTS: Of 369 PDAC cases identified, 35 (9.5%) were EOPC.
      Compared to older patients, EOPC patients were more frequently male (71% vs 54%,
      p = 0.043) and less commonly of British origin (37% vs 70%, p = 0.002). There was
      no significant difference regarding the prevalence of any of the risk factors
      known to be associated with older PDAC patients. Fewer EOPC patients presented
      with resectable disease (23% vs 44%, p = 0.015) and more received adjuvant
      chemo/radiotherapy (60% vs 46%, p = 0.008). The overall median survival and stage
      specific survival did not differ significantly between the two groups, although a
      longer survival for localized disease was seen in EOPC patients (25 months (12.9
      37, 95%CI) vs 13 months (10.5-15.5 95%CI) for older PDAC patients). CONCLUSIONS:
      The EOPC patients had different demographics and were more likely than their
      older PDAC counterparts to be male. Typically they presented with more advanced
      disease, received more aggressive treatment, and had on overall similar survival
      outcome.

PMID- 30208960
TI  - Combat lifesaver-trained, first-responder application of junctional tourniquets:
      a prospective, randomized, crossover trial.
AB  - BACKGROUND: Junctional hemorrhage surpassed extremity hemorrhage as the leading
      cause of preventable death after the resurgence of limb tourniquets during the
      recent conflicts in Afghanistan and Iraq. Junctional tourniquets (JTQs) were
      developed in response to this injury pattern. Published data for JTQ efficacy are
      limited and do not incorporate nonmedical, military first responders. We compared
      the time for effective placement and scores for device satisfaction between two
      different JTQs, stratified by combat lifesaver (CLS) and combat medics. METHODS:
      We performed a prospective, randomized, crossover trial utilizing the SAM(r)
      Medical Junctional Tourniquet (SJT) and Junctional Emergency Treatment Tool
      (JETTTM). Investigators simple randomized CLS and combat medics to SJT or JETT
      for their first JTQ application on mannequins with penetrating inguinal injuries.
      Then, participants immediately placed the other JTQ on another casualty with the
      same injury. The primary outcome measured was time of successful application.
      Success was defined as proper JTQ placement and a pressure reading of at least
      180 mmHg. We compared outcomes between CLS and combat medics. Unsuccessful JTQ
      applications were excluded from the comparative analysis. RESULTS: From June 2015
      to August 2015, a total of 227 personnel (133 CLS and 94 combat medics) at Fort
      Hood, Texas, USA volunteered to participate in the study. Twenty-eight percent
      (38 of 133) of CLS and 40% (38 of 94) of combat medics placed both JTQs
      successfully, for a total of 152 applications (76 SJTs and 76 JETTs). We found a
      significant difference between applications of the JETT between the CLS and
      combat medics (92.0 +/- 37.7 s versus 70.5 +/- 20.5 s, P = 0.004). No other
      subgroup analyses, whether by device or user, demonstrated a significant
      difference in application time. Both groups preferred the SJT over the JETT. CLS
      disagreed with combat medics that the JETT could be easily applied by one person
      (median 3.0 [2.0, 4.0] versus median 4.0 [3.0, 5.0]; P = 0.006). CONCLUSION:
      Overall, success rates for both the SJT and JETT were low. Improved training is
      needed to increase successful application of junctional tourniquets before
      widespread implementation. Combat lifesavers and combat medics prefer the SJT
      over the JETT.

PMID- 30208961
TI  - Sex ratio in dementia with Lewy bodies balanced between Alzheimer's disease and
      Parkinson's disease dementia: a cross-sectional study.
AB  - BACKGROUND: Gender distribution varies across neurodegenerative disorders, with,
      traditionally, a higher female frequency reported in Alzheimer's disease (AD) and
      a higher male frequency in Parkinson's disease (PD). Conflicting results on
      gender distribution are reported concerning dementia with Lewy bodies (DLB),
      usually considered as an intermediate disease between AD and PD. The aim of the
      present study was to investigate gender differences in DLB in French specialized
      memory settings using data from the French national database spanning from 2010
      to 2015 and to compare sex ratio in DLB with that in AD, Parkinson's disease
      dementia (PDD), and PD. Our hypothesis was that there is a balanced sex ratio in
      DLB, different from that found in AD and PD. METHODS: We conducted a repeated
      cross-sectional study. The study population comprised individuals with a DLB, AD,
      PDD, or PD diagnosis according to the International Classification of Diseases,
      Tenth Revision, in the French National Alzheimer Database between 2010 and 2015.
      Sex ratio and demographic data were compared using multinomial logistic
      regression and a Bayesian statistical model. RESULTS: From 2010 to 2015 in French
      specialized memory settings, sex ratios (female percent/male percent) were found
      as follows: 1.21 (54.7%/45.3%) for DLB (n = 10,309), 2.34 (70.1%/29.9%) for AD (n
      = 135,664), 0.76 (43.1%/56.9%) for PD (n = 8744), and 0.83 (45.4%/54.6%) for PDD
      (n = 3198). Significant differences were found between each group, but not
      between PDD and PD, which had a similar sex ratio. CONCLUSIONS: This large-sample
      prevalence study confirms the balanced gender distribution in the DLB population
      compared with AD and PD-PDD. Gender distribution and general demographic
      characteristics differed between DLB and PDD. This is consistent with the
      hypothesis that DLB is a distinct disease with characteristics intermediate
      between AD and PD, as well as with the hypothesis that DLB could have at least
      partially distinct neuropathological correlates.

PMID- 30208962
TI  - Root exudates drive the soil-borne legacy of aboveground pathogen infection.
AB  - BACKGROUND: Plants are capable of building up beneficial rhizosphere communities
      as is evidenced by disease-suppressive soils. However, it is not known how and
      why soil bacterial communities are impacted by plant exposure to foliar pathogens
      and if such responses might improve plant performance in the presence of the
      pathogen. Here, we conditioned soil by growing multiple generations (five) of
      Arabidopsis thaliana inoculated aboveground with Pseudomonas syringae pv tomato
      (Pst) in the same soil. We then examined rhizosphere communities and plant
      performance in a subsequent generation (sixth) grown in pathogen-conditioned
      versus control-conditioned soil. Moreover, we assessed the role of altered root
      exudation profiles in shaping the root microbiome of infected plants. RESULTS:
      Plants grown in conditioned soil showed increased levels of jasmonic acid and
      improved disease resistance. Illumina Miseq 16S rRNA gene tag sequencing revealed
      that both rhizosphere and bulk soil bacterial communities were altered by Pst
      infection. Infected plants exhibited significantly higher exudation of amino
      acids, nucleotides, and long-chain organic acids (LCOAs) (C > 6) and lower
      exudation levels for sugars, alcohols, and short-chain organic acids (SCOAs) (C
      <= 6). Interestingly, addition of exogenous amino acids and LCOA also elicited a
      disease-suppressive response. CONCLUSION: Collectively, our data suggest that
      plants can recruit beneficial rhizosphere communities via modification of plant
      exudation patterns in response to exposure to aboveground pathogens to the
      benefit of subsequent plant generations.

PMID- 30208964
TI  - Patient preference survey: are patients willing to delay surgery if obstructive
      sleep apnea is suspected?
AB  - BACKGROUND: Screening and optimizing patients for OSA in the perioperative period
      may reduce postoperative complications. However, sleep studies can be difficult
      to obtain before surgery. Previous surveys reported that the majority of sleep
      physicians would delay surgery to diagnose and manage OSA, but most
      anesthesiologists would not. While disagreements exist, the importance of shared
      decision making and patient preferences have never been studied on this topic. It
      is unknown whether patients with suspected OSA, when given information about OSA,
      would be willing to delay surgery to diagnose and manage their condition
      preoperatively. METHODS: This study consisted of a self-administered
      questionnaire that surveyed patients, patient relatives, or any accompanying
      members. The survey was conducted in the preoperative clinic or in the
      perioperative patient and family waiting area at two hospitals in Canada and in
      the United States. A hypothetical scenario was used: participants were given
      information about OSA, and asked about their preferences regarding preoperative
      management should they be at risk for OSA in the setting of pending elective
      surgery. The objective of this study was to determine whether respondents
      preferred to 1) proceed with surgery as planned, 2) delay surgery to ensure the
      medical condition of OSA is diagnosed and optimized, or 3) let his/her physician
      decide. RESULTS: The final survey contained 19 questions and the survey was
      conducted from June 2016 to September 2016. Four hundred and seventy-three
      surveys were collected. Forty-four percent of respondents, when given information
      about OSA, preferred to delay surgery pending a sleep study and treatment. Forty
      percent of respondents who preferred to delay surgery would tolerate delaying up
      to two months. CONCLUSION: Increasing emphasis and significant value has been
      placed on shared-decision making between patients and physicians. Educating
      patients about the risks of OSA and incorporating patient preferences into the
      perioperative management of OSA may be warranted.

PMID- 30208963
TI  - Oral immunization with a novel attenuated Salmonella Gallinarum encoding
      infectious bronchitis virus spike protein induces protective immune responses
      against fowl typhoid and infectious bronchitis in chickens.
AB  - Fowl typhoid (FT), a septicemic disease caused by Salmonella Gallinarum (SG), and
      infectious bronchitis (IB) are two economically important avian diseases that
      affect poultry industry worldwide. Herein, we exploited a live attenuated SG
      mutant, JOL967, to deliver spike (S) protein 1 of IB virus (V) to elicit
      protective immunity against both FT and IB in chickens. The codon optimized S1
      nucleotide sequence was cloned in-frame into a prokaryotic constitutive
      expression vector, pJHL65. Subsequently, empty pJHL65 or recombinant pJHL65-S1
      plasmid was electroporated into JOL967 and the resultant clones were designated
      as JOL2068 and JOL2077, respectively. Our results demonstrated that the chickens
      vaccinated once orally with JOL2077 elicited significantly (p < 0.05) higher IBV
      specific humoral and cell-mediated immunity compared to JOL2068 and PBS control
      groups. Consequently, on challenge with the virulent IBV strain at 28th day post
      vaccination, JOL2077 vaccinated birds displayed significantly (p < 0.05) lower
      inflammatory lesions in virus-targeted tissues compared to control groups.
      Furthermore, 33.3% (2 of 6) of birds vaccinated with JOL2077 vaccine had shown
      virus recovery from tracheal tissues compared to 100% (6 of 6) recovery obtained
      in both the control groups. Against wild-type SG lethal challenge, both JOL2077
      and JOL2068 vaccinated groups exhibited only 10% mortality compared to 80%
      mortality observed in PBS control group. In conclusion, we show that JOL2077 can
      induce efficient IBV- and carrier-specific protective immunity and can act as a
      bivalent vaccine against FT and IB. Further studies are warranted to investigate
      the potential of JOL2077 vaccine in broiler and young layer birds.

PMID- 30208965
TI  - Fidelity assessment of the suicide reporting guidelines in Korean newspapers.
AB  - BACKGROUND: With the dishonor of being the highest suicide rated country in
      Organisation for Economic Co-operation and Development, South Korea should take
      more initiatives in suicide prevention. Although the role of the media and its
      relation to actual suicide attempts has been tested and supported by many
      studies, the suicide reporting guidelines are not well followed. The purpose of
      this study is to examine how well Korean newspapers adhere to existing guidelines
      and to suggest limitation and improvements for the current guidelines. METHODS:
      Five mainstream newspapers in South Korea, namely, Kyunghyang Shinmun, Hankyoreh,
      Chosun Ilbo, JoongAng Daily, and Dong-A Ilbo, were chosen for the analysis. Using
      the Naver news search engine, articles dated from January 1, 2014, to December
      31, 2017, were selected with the keyword "suicide" and advanced option "printed
      newspaper." However, articles, columns, opinions, and reviews that utilized the
      word "suicide" in a general context were excluded from the final analysis.
      Finally, the number of cases was narrowed down to 368. Each article was analyzed
      using the guideline framework consisting of 13 items: sensational coverage,
      overstatement, direct wording, method used, details about site/location,
      photographs, suicide note, generalization, speculation, romanticization,
      interviews with the bereaved, help-seeking information, and public education.
      RESULTS: More than 60% of the articles included direct wording (63.9%), mentioned
      the method used (68.2%), and provided details about the site or location (74.5%).
      Nearly half of the articles revealed the contents of the suicide note (44.6%).
      Less than 3% of the suicide reports had information about hotline logo or phone
      numbers (1.4%) and facts regarding suicide and suicide prevention (2.2%).
      CONCLUSIONS: Our study revealed that the guidelines were ineffective in their
      monitoring role and that most of the newspapers were incompliant with many
      significant guideline items in South Korea. Our findings not only explore the
      limitations of the current guidelines but also provide an important rationale as
      to why there should be stronger suicide monitoring regulation or an agency with
      sufficient authority to prevent suicide in a nation-wide scale.

PMID- 30208966
TI  - Preserving prion strain identity upon replication of prions in vitro using
      recombinant prion protein.
AB  - Last decade witnessed an enormous progress in generating authentic infectious
      prions or PrPSc in vitro using recombinant prion protein (rPrP). Previous work
      established that rPrP that lacks posttranslational modification is able to
      support replication of highly infectious PrPSc with assistance of cofactors of
      polyanionic nature and/or lipids. Unexpectedly, previous studies also revealed
      that seeding of rPrP by brain-derived PrPSc gave rise to new prion strains with
      new disease phenotypes documenting loss of a strain identity upon replication in
      rPrP substrate. Up to now, it remains unclear whether prion strain identity can
      be preserved upon replication in rPrP. The current study reports that faithful
      replication of hamster strain SSLOW could be achieved in vitro using rPrP as a
      substrate. We found that a mixture of phosphatidylethanolamine (PE) and synthetic
      nucleic acid polyA was sufficient for stable replication of hamster brain-derived
      SSLOW PrPSc in serial Protein Misfolding Cyclic Amplification (sPMCA) that uses
      hamster rPrP as a substrate. The disease phenotype generated in hamsters upon
      transmission of recombinant PrPSc produced in vitro was strikingly similar to the
      original SSLOW diseases phenotype with respect to the incubation time to disease,
      as well as clinical, neuropathological and biochemical features. Infrared
      microspectroscopy (IR-MSP) indicated that PrPSc produced in animals upon
      transmission of recombinant PrPSc is structurally similar if not identical to the
      original SSLOW PrPSc. The current study is the first to demonstrate that rPrP can
      support replication of brain-derived PrPSc while preserving its strain identity.
      In addition, the current work is the first to document that successful
      propagation of a hamster strain could be achieved in vitro using hamster rPrP.

PMID- 30208967
TI  - Validation of the Polish version of the Western Ontario Rotator Cuff Index in
      patients following arthroscopic rotator cuff repair.
AB  - BACKGROUND: The Western Ontario Rotator Cuff Index (WORC) is a joint specific
      outcome tool that assesses the quality of life in patients with various rotator
      cuff problems. Our purpose was to evaluate selected psychometric characteristics
      (internal consistency, validity, reliability and agreement) of the Polish version
      of WORC in patients undergoing rotator cuff repair. METHODS: Sixty-nine subjects
      took part in the study with a mean age 55.5 (range 40-65). All had undergone
      arthroscopic rotator cuff repair in 2015-2016. Data from 57 patients in whom
      symptoms in the shoulder joint had not changed within 10-14 days were analyzed in
      a WORC test-retest using the Intraclass Correlation Coefficient (ICC), Standard
      Error of Measurement (SEM) and Minimal Detectable Change (MDC). WORC was compared
      to the short version of the Disabilities of Arm, Shoulder and Hand Questionnaire
      (QuickDash) and the Short Form-36 v. 2.0 (SF-36). RESULTS: High internal
      consistency of 0.94 was found using Cronbach's alpha coefficient. Reliability of
      the WORC resulted in ICC = 0.99, agreement assessed with SEM and MDC amounted to
      1.62 and 4.48 respectively. The validity analysis of WORC showed strong
      correlations with QuickDash and SF-36 PCS (Physical Component Summary), while
      moderate with SF-36 MCS (Mental Component Summary). WORC had no floor or ceiling
      effect. CONCLUSIONS: The Polish version of the WORC is a reliable and valid tool
      with high internal consistency for assessing the quality of life in patients
      undergoing arthroscopic rotator cuff repair.

PMID- 30208968
TI  - The association of socioeconomic and clinical characteristics with health-related
      quality of life in patients with psoriasis: a cross-sectional study.
AB  - BACKGROUND: This study aimed to determine the socioeconomic and clinical
      characteristics affecting health-related quality of life (HRQoL) in patients with
      psoriasis. METHODS: A cross-sectional study was conducted between March and June
      2015 using data obtained via an Internet-based survey completed by a psoriasis
      patient group in Korea. The survey included items regarding demographic,
      socioeconomic, and clinical characteristics and HRQoL. Patients' HRQoL impairment
      was classified as severe if their Dermatology Life Quality Index Scores were >=
      11. Factors influencing HRQoL impairment were identified using multivariate
      logistic regression analysis. RESULTS: Of the 299 respondents, 161 (53.8%)
      exhibited severe HRQoL impairment. The Dermatology Life Quality Index scores were
      significantly associated with gender, annual income, neck psoriasis, psoriasis
      related resignation from work, and use of oral and herbal medications. The
      severity of HRQoL impairment in women was twice that observed in men (odds ratio
      [OR] = 2.00, 95% confidence interval (CI): 1.05-3.80). Patients with psoriasis on
      the neck exhibited significantly greater HRQoL impairment than those with
      psoriasis on other areas of their bodies (OR = 2.30, 95% CI: 1.20-4.43). With
      respect to the socioeconomic status, patients who earned > 40 million KRW
      (approximately 34,000 USD; high-income group) showed less HRQoL impairment
      compared with those who had lower incomes (OR = 0.47, 95% CI: 0.28-0.80).
      Patients with severe HRQoL impairment used oral (OR = 2.04, 95% CI: 1.20-3.44)
      and herbal (OR = 1.86, 95% CI: 1.04-3.34) medications more often relative to
      patients with less severe HRQoL impairment. CONCLUSIONS: HRQoL in patients with
      psoriasis was significantly associated with their demographic and socioeconomic
      characteristics and employment status. The presence of psoriasis on exposed areas
      of the body was significantly associated with patients' HRQoL and employment
      status. Further research is required to evaluate the impact of psoriasis on
      patients' productivity.

PMID- 30208969
TI  - Change in the prevalence asthma, rhinitis and respiratory symptom over a 20 year
      period: associations to year of birth, life style and sleep related symptoms.
AB  - BACKGROUND: The aim of this investigation was to study change in adults over a 20
      year period in the prevalence of respiratory symptoms and disorders and its
      association to year of birth, life style and sleep related variables. METHOD:
      Adults 20-44 years of age, 6085 women and 5184 men, were randomly selected from
      seven centres in Northern Europe and followed for 20 years. The number of
      participants in the first survey was 21,595 and 11,269 participated in all three
      surveys. The participants were divided into three birth cohorts: 1944-1955, 1956
      1965 and 1966-1975. RESULTS: During the 20 year period the prevalence of wheeze
      decreased (- 2%) and the prevalence of asthma (+ 4%) and allergic rhinitis (+ 5%)
      increased, whereas the prevalence of nocturnal respiratory symptoms was
      relatively unchanged. The increase in allergic rhinitis was largest in those born
      1966 to 1975 except in Estonia. There was large decrease in smoking (- 20%),
      increase in obesity (+ 7%) and snoring (+ 6%) during the study period. Smoking,
      obesity, snoring and nocturnal gastroesophageal reflux (nGER) were related to a
      higher risk of all symptoms. Obesity, snoring and nGER were also independently
      related to asthma. CONCLUSION: We conclude that as our participants got older
      there was a decrease in wheeze, no change in nocturnal symptoms and an increase
      in reported asthma and allergic rhinitis. These changes in prevalence are
      probably related to a decrease in smoking being counteracted by an increase in
      allergy, obesity and sleep related disorders.

PMID- 30208970
TI  - Differential responses of MET activations to MET kinase inhibitor and
      neutralizing antibody.
AB  - BACKGROUND: Aberrant MET tyrosine kinase signaling is known to cause cancer
      initiation and progression. While MET inhibitors are in clinical trials against
      several cancer types, the clinical efficacies are controversial and the molecular
      mechanisms toward sensitivity remain elusive. METHODS: With the goal to
      investigate the molecular basis of MET amplification (METamp) and hepatocyte
      growth factor (HGF) autocrine-driven tumors in response to MET tyrosine kinase
      inhibitors (TKI) and neutralizing antibodies, we compared cancer cells harboring
      METamp (MKN45 and MHCCH97H) or HGF-autocrine (JHH5 and U87) for their sensitivity
      and downstream biological responses to a MET-TKI (INC280) and an anti-MET
      monoclonal antibody (MetMab) in vitro, and for tumor inhibition in vivo. RESULTS:
      We find that cancer cells driven by METamp are more sensitive to INC280 than are
      those driven by HGF-autocrine activation. In METamp cells, INC280 induced a DNA
      damage response with activation of repair through the p53BP1/ATM signaling
      pathway. Although MetMab failed to inhibit METamp cell proliferation and tumor
      growth, both INC280 and MetMab reduced HGF-autocrine tumor growth. In addition,
      we also show that HGF stimulation promoted human HUVEC cell tube formation via
      the Src pathway, which was inhibited by either INC280 or MetMab. These
      observations suggest that in HGF-autocrine tumors, the endothelial cells are the
      secondary targets MET inhibitors. CONCLUSIONS: Our results demonstrate that
      METamp and HGF-autocrine activation favor different molecular mechanisms. While
      combining MET TKIs and ATM inhibitors may enhance the efficacy for treating
      tumors harboring METamp, a combined inhibition of MET and angiogenesis pathways
      may improve the therapeutic efficacy against HGF-autocrine tumors.

PMID- 30208971
TI  - Effect of action-based cognitive remediation on cognition and neural activity in
      bipolar disorder: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Cognitive impairment is present in bipolar disorder (BD) during the
      acute and remitted phases and hampers functional recovery. However, there is
      currently no clinically available treatment with direct and lasting effects on
      cognitive impairment in BD. We will examine the effect of a novel form of
      cognitive remediation, action-based cognitive remediation (ABCR), on cognitive
      impairment in patients with BD, and explore the neural substrates of potential
      treatment efficacy on cognition. METHODS/DESIGN: The trial has a randomized,
      controlled, parallel-group design. In total, 58 patients with BD in full or
      partial remission aged 18-55 years with objective cognitive impairment will be
      recruited. Participants are randomized to 10 weeks of ABCR or a control group.
      Assessments encompassing neuropsychological testing and mood ratings, and
      questionnaires on subjective cognitive complaints, psychosocial functioning, and
      quality of life are carried out at baseline, after 2 weeks of treatment, after
      the end of treatment, and at a six-month-follow-up after treatment completion.
      Functional magnetic resonance imaging scans are performed at baseline and 2 weeks
      into treatment. The primary outcome is a cognitive composite score spanning
      verbal memory, attention, and executive function. Two complete data sets for 52
      patients will provide a power of 80% to detect a clinically relevant between
      group difference on the primary outcome. Behavioral data will be analyzed using
      mixed models in SPSS while MRI data will be analyzed with the FMRIB Expert
      Analysis Tool (FEAT). Early treatment-related changes in neural activity from
      baseline to week 2 will be investigated for the dorsal prefrontal cortex and
      hippocampus as the regions of interest and with an exploratory whole-brain
      analysis. DISCUSSION: The results will provide insight into whether ABCR has
      beneficial effects on cognition and functioning in remitted patients with BD. The
      results will also provide insight into early changes in neural activity
      associated with improvement of cognition, which can aid future treatment
      development. TRIAL REGISTRATION: Clinicaltrials.gov , NCT03295305 . Registered on
      26 September 2017.

PMID- 30208975
TI  - Volumetric analysis of vocal fold atrophy via magnetic resonance imaging.
AB  - OBJECTIVE: To quantitatively test the hypothesis that older patients have
      increased thyroarytenoid muscle atrophy by comparing thyroarytenoid muscle
      volumes across different age groups. METHODS: A retrospective chart review was
      conducted. The study included 111 patients with no history of laryngeal
      pathology. Two investigators reviewed magnetic resonance imaging studies of these
      patients and manually traced the thyroarytenoid muscles on multiple slices
      bilaterally. Thyroarytenoid muscle volumes were then computed using imaging
      analysis software. Patients were stratified into three age groups (18-50 years,
      51-64 years, and 65 years or older) for comparison. RESULTS: Intra- and inter
      rater reliabilities were excellent for all measurements (intraclass correlation
      co-efficient > 0.90). There was no statistically significant difference in the
      mean volumes of left and right thyroarytenoid muscles in all age and gender
      groups. CONCLUSION: Given the lack of statistically significant difference in
      thyroarytenoid muscle volume between age groups on magnetic resonance imaging,
      the prevailing assumption that age-related thyroarytenoid muscle atrophy
      contributes to presbyphonia should be re-examined.

PMID- 30208976
TI  - Consistency and replicability of a pharmacist-led intervention for asthma
      patients: Italian Medicines Use Review (I-MUR).
AB  - : AimThis study aimed to assess the consistency and replicability of these
      process measures during provision of the Italian Medicines Use Review (I-MUR).
      BACKGROUND: Medication review is a common intervention provided by community
      pharmacists in many countries, but with little evidence of consistency and
      replicability. The I-MUR utilised a standardised question template in two
      separate large-scale studies. The template facilitated pharmacists in recording
      medicines and problems reported by patients, the pharmaceutical care issues
      (PCIs) they found and actions they took to improve medicines use. METHODS:
      Community pharmacists from four cities and across 15 regions were involved in the
      two studies. Patients included were adults with asthma. Medicines use, adherence,
      asthma problems, PCIs and actions taken by pharmacists were compared across
      studies to assess consistency and replicability of I-MUR.FindingsThe total number
      of pharmacists and patients completing the studies was 275 and 1711,
      respectively. No statistically significant differences were found between the
      studies in the following domains: patients' demographic, patients' perceived
      problems, adherence, asthma medicines used and healthy living advice provided by
      pharmacists. The proportion of patients in which pharmacists identified PCIs was
      similar across both studies. There were differences only in the incidence of non
      steroidal anti-inflammatory drug use, the frequency of potential drug-disease
      interactions and in the types of advice given to patients and GPs. CONCLUSIONS:
      The use of a standardised template for the I-MUR may have contributed to a degree
      of consistency in the issues found, which suggests this intervention could have
      good replicability.

PMID- 30208973
TI  - Cycles of gene expression and genome response during mammalian tissue
      regeneration.
AB  - BACKGROUND: Compensatory liver hyperplasia-or regeneration-induced by two-thirds
      partial hepatectomy (PH) permits the study of synchronized activation of
      mammalian gene expression, particularly in relation to cell proliferation. Here,
      we measured genomic transcriptional responses and mRNA accumulation changes after
      PH and sham surgeries. RESULTS: During the first 10-20 h, the PH- and sham
      surgery responses were very similar, including parallel early activation of cell
      division-cycle genes. After 20 h, however, whereas post-PH livers continued with
      a robust and coordinate cell-division-cycle gene-expression response before
      returning to the resting state by 1 week, sham-surgery livers returned directly
      to a resting gene-expression state. Localization of RNA polymerase II (Pol II),
      and trimethylated histone H3 lysine 4 (H3K4me3) and 36 (H3K36me3) on genes
      dormant in the resting liver and activated during the PH response revealed a
      general de novo promoter Pol II recruitment and H3K4me3 increase during the early
      10-20 h phase followed by Pol II elongation and H3K36me3 accumulation in gene
      bodies during the later proliferation phase. H3K36me3, generally appearing at the
      first internal exon, was preceded 5' by H3K36me2; 3' of the first internal exon,
      in about half of genes H3K36me3 predominated and in the other half H3K36me2 and
      H3K36me3 co-existed. Further, we observed some unusual gene profiles with
      abundant Pol II but little evident H3K4me3 or H3K36me3 modification, indicating
      that these modifications are neither universal nor essential partners to Pol II
      transcription. CONCLUSIONS: PH and sham surgical procedures on mice reveal
      striking early post-operatory gene expression similarities followed by
      synchronized mRNA accumulation and epigenetic histone mark changes specific to
      PH.

PMID- 30208977
TI  - Analysis of smoking behaviour in patients with peritonsillar abscess: a
      prospective, matched case-control study.
AB  - OBJECTIVE: Smoking is purported to increase the risk of peritonsillar abscess
      formation, but prospective data are needed to confirm this hypothesis. This
      prospective study aimed to identify this correlation. METHODS: Fifty-four
      patients with peritonsillar abscess were prospectively asked about their smoking
      behaviour using a questionnaire that was designed and approved by the Robert Koch
      Institute (Berlin, Germany) to analyse smoking behaviour in epidemiological
      studies. Afterwards, a consecutive control group (without peritonsillar abscess),
      matched in terms of age and gender, was surveyed using the same questionnaire. A
      classification of smoker, former smoker and non-smoker was made, and the numbers
      of pack-years were calculated and compared. RESULTS: Statistical analysis of both
      groups revealed a significant correlation between peritonsillar abscess and
      smoking experience (p = 0.025). Moreover, there were significantly fewer non
      smokers in the non-peritonsillar abscess group (p = 0.04). The number of pack
      years was higher in the peritonsillar abscess group (p = 0.037). CONCLUSION:
      There is a statistically significant association between peritonsillar abscess
      and smoking.

PMID- 30208972
TI  - Regulation of the master regulator FOXM1 in cancer.
AB  - FOXM1 (forkhead box protein M1) is a critical proliferation-associated
      transcription factor that is widely spatiotemporally expressed during the cell
      cycle. It is closely involved with the processes of cell proliferation, self
      renewal, and tumorigenesis. In most human cancers, FOXM1 is overexpressed, and
      this indicates a poor prognosis for cancer patients. FOXM1 maintains cancer
      hallmarks by regulating the expression of target genes at the transcriptional
      level. Due to its potential role as molecular target in cancer therapy, FOXM1 was
      named the Molecule of the Year in 2010. However, the mechanism of FOXM1
      dysregulation remains indistinct. A comprehensive understanding of FOXM1
      regulation will provide novel insight for cancer and other diseases in which
      FOXM1 plays a major role. Here, we summarize the transcriptional regulation, post
      transcriptional regulation and post-translational modifications of FOXM1, which
      will provide extremely important implications for novel strategies targeting
      FOXM1.

PMID- 30208974
TI  - Potential of Aedes aegypti populations in Madeira Island to transmit dengue and
      chikungunya viruses.
AB  - BACKGROUND: Aedes spp. mosquitoes mainly transmit the arboviruses dengue virus
      (DENV) and chikungunya virus (CHIKV) in urban areas, causing a severe public
      health problem. In 2012-2013, a major dengue outbreak occurred on Madeira Island
      where the mosquito Aedes aegypti was the only vector. Up to now, the competence
      of Ae. aegypti populations from Madeira to transmit DENV or CHIKV remains
      unknown. This study aimed to assess experimentally the ability of Ae. aegypti
      populations from Madeira to transmit these viruses. RESULTS: By orally exposing
      mosquitoes to CHIKV (NC/2011-568) and DENV-2 (Bangkok), the vector competence of
      two field-collected Ae. aegypti populations, i.e. Funchal and Paul do Mar, was
      evaluated. We found that both populations were similarly infected and ensured the
      dissemination and transmission of CHIKV at the same rates. With DENV-2, viral
      dissemination was significantly higher in the Funchal population compared to Paul
      do Mar. We found no significant differences in transmission rates between
      populations. CONCLUSIONS: To our knowledge, this study has demonstrated for the
      first time the ability of temperate European Ae. aegypti populations from Madeira
      to transmit DENV and CHIKV. As our results suggest, there is a potential risk for
      the local transmission of DENV and CHIKV if introduced to Madeira or continental
      Europe where Aedes albopictus is present. Our results highlight the need for
      continuing vector surveillance and control on Madeira Island to future-proof the
      Island against mosquito-borne epidemics.

PMID- 30208978
TI  - Temporal relationship between occurrences of hand, foot and mouth disease,
      respiratory virus detection and febrile seizures in children in tropical
      Singapore: a time-series analysis.
AB  - Febrile seizure (FS) in children is a common complication of infections with
      respiratory viruses and hand, foot and mouth disease (HFMD). We conducted a
      retrospective ecological time-series analysis to determine the temporal
      relationship between hospital attendances for FS and HFMD or respiratory virus
      infections. Epilepsy attendance was used as a control. Data from 2004 to 2012 FS
      and epilepsy hospital attendance, HFMD notifications to the Ministry of Health
      and from laboratory-confirmed viral respiratory infections among KK Women's and
      Children's Hospital inpatients were used. A multivariate linear regression
      analysis was conducted to evaluate the relationship between FS and the virus time
      series. Relative risks of FS by age were calculated using Bayesian statistical
      methods. Paediatric accident and emergency (A&E) attendances for FS were found to
      be associated with influenza A (extra 0.47 FS per influenza A case), B (extra
      0.32 per influenza B case) and parainfluenza 3 (extra 0.35 per parainfluenza type
      3 case). However, other viruses were not significantly associated with FS. None
      of the viruses were associated with epileptic seizure attendance. Influenza A, B
      and parainfluenza 3 viruses contributed to the burden of FS resulting in A&E
      attendance. Children at risk of FS should be advised to receive seasonal
      influenza vaccination.

PMID- 30208979
TI  - Multiple nutritional factors and thyroid disease, with particular reference to
      autoimmune thyroid disease.
AB  - Hashimoto's thyroiditis (HT) and Graves' disease (GD) are examples of autoimmune
      thyroid disease (AITD), the commonest autoimmune condition. Antibodies to thyroid
      peroxidase (TPO), the enzyme that catalyses thyroid-hormone production and
      antibodies to the receptor for the thyroid-stimulating hormone, are
      characteristic of HT and GD, respectively. It is presently accepted that genetic
      susceptibility, environmental factors, including nutritional factors and immune
      disorders contribute to the development of AITD. Aiming to investigate the effect
      of iodine, iron and selenium in the risk, pathogenesis and treatment of thyroid
      disease, PubMed and the Cochrane Library were searched for relevant publications
      to provide a narrative review. Iodine: chronic exposure to excess iodine intake
      induces autoimmune thyroiditis, partly because highly-iodinated thyroglobulin
      (Tg) is more immunogenic. The recent introduction of universal salt iodisation
      can have a similar, although transient, effect. Iron: iron deficiency impairs
      thyroid metabolism. TPO is a haem enzyme that becomes active only after binding
      haem. AITD patients are frequently iron-deficient since autoimmune gastritis,
      which reduces iron absorption and coeliac disease which causes iron loss, are
      frequent co-morbidities. In two-thirds of women with persistent symptoms of
      hypothyroidism despite appropriate levothyroxine therapy, restoration of serum
      ferritin above 100 ug/l ameliorated symptoms. Selenium: selenoproteins are
      essential to thyroid action. In particular, the glutathione peroxidases remove
      excessive hydrogen peroxide produced there for the iodination of Tg to form
      thyroid hormones. There is evidence from observational studies and randomised
      controlled trials that selenium, probably as selenoproteins, can reduce TPO
      antibody concentration, hypothyroidism and postpartum thyroiditis. Appropriate
      status of iodine, iron and selenium is crucial to thyroid health.

PMID- 30208980
TI  - Psychoses sans Frontieres: towards an interdisciplinary understanding of
      psychosis risk amongst migrants and their descendants.
AB  - Understanding the excess risk of psychotic disorders in migrant and ethnic
      minority groups has long been an important research focus in psychiatric
      epidemiology and public mental health. Heterogeneity between migrant groups based
      on the region of origin, minority status and other socioeconomic factors may
      provide clues as to the underlying aetiological mechanisms explaining this risk,
      as well as informing our general understanding of psychotic disorders.
      Nonetheless, disentangling the mechanisms underlying this association has been
      the focus of more speculation and theory to date than empirical research. Now
      more than ever, we need to move beyond studies which demonstrate excess rates in
      migrant and ethnic minority groups to novel population-based studies which
      identify the determinants and mechanisms through which this risk is shaped. In
      this paper, we review the main hypotheses proposed to explain these disparities
      and the current level of support for them. We then highlight recent evidence from
      epidemiology and neuroscience which provides important new clues in our
      understanding of the aetiology of psychotic disorders. We concluded with
      suggestions for future interdisciplinary research to prevent this public mental
      health inequality within a generation.

PMID- 30208981
TI  - The neural basis of hostility-related dimensions in schizophrenia.
AB  - Hostility and related dimensions like anger, urgency, impulsivity and
      aggressiveness have been described in non-clinical populations and various
      serious mental illnesses including schizophrenia. Although representing a mental
      healthcare challenge, the investigation of such constructs is often limited by
      the presence of complex and multi-factorial causes and lack of agreement in their
      conceptualisation and measurement. In this review, we aim to clarify the
      anatomical basis of hostility-related dimensions in schizophrenia. Imaging
      studies suggest malfunctioning of a neural circuitry including amygdala,
      striatum, prefrontal cortex, anterior cingulate cortex, insula and hippocampus to
      modulate hostile thoughts and behaviours, at least in the subgroup of patients
      with schizophrenia who exhibit high levels of urgency, impulsivity and
      aggressiveness.

PMID- 30208982
TI  - Sex differences in relation patterns between health-related quality of life of
      older adults and its correlates: a population-based cross-sectional study in
      Madeira, Portugal.
AB  - A population-based cross-sectional study aimed to examine sex differences in
      health-related quality of life (HRQoL) of older adults, and investigate whether
      the relation patterns between HRQoL and its correlates differed between sexes. A
      stratified proportional and representative sample included 802 volunteers, aged
      60-79. HRQoL (36-item Short Form Health Survey), functional fitness (Senior
      Fitness Test), physical activity (PA) (Baecke questionnaire), demographic
      information and health features (questionnaires) were assessed. Men showed
      significantly higher HRQoL (P<0.001). Body mass index, body strength, aerobic
      endurance, PA, depressive symptoms, falls, and living alone were significantly
      related to HRQoL. With sex as moderator, these relations were not significant,
      except for PA (beta=0.12, P=0.004). A significant interaction of sex with PA on
      HRQoL (beta=0.08, P=0.037) was found, indicating that this relation was higher in
      men. A similar relation pattern was found for HRQoL physical component. HRQoL and
      its correlates differed between sexes, demanding a sex specific approach to
      promote HRQoL.

PMID- 30208983
TI  - Streamlining grommet pathways for otitis media with effusion and hearing loss in
      children: our experience.
AB  - BACKGROUND: Grommet insertion is a common surgical procedure in children. Long
      waiting times for grommet insertion are not unusual. This project aimed to
      streamline the process by introducing a pathway for audiologists to directly
      schedule children meeting National Institute for Health and Care Excellence
      Clinical Guideline 60 ('CG60') for grommet insertion.Method and resultsA period
      from June to November 2014 was retrospectively audited. Mean duration between the
      first audiology appointment and grommet insertion was 294.5 days (median = 310
      days). Implementing the direct-listing pathway reduced the duration between first
      audiology appointment and grommet insertion (mean = 232 days; median = 231 days).
      There has been a reduction in the time between the first audiology appointment
      and surgery (mean difference of 62.5 days; p = 0.024), and a reduction in the
      time between second audiology appointment and surgery (28 days; p = 0.009).
      CONCLUSION: Direct-listing pathways for grommet insertion can reduce waiting
      times and expedite surgery. Implementation involves a simple alteration of
      current practice, adhering to National Institute for Health and Care Excellence
      Clinical Guideline 60. The ultimate decision regarding surgery still rests with
      ENT specialists.

PMID- 30208984
TI  - Impact of Patients Presenting with Alcohol and/or Drug Intoxication on In-Event
      Health Care Services at Mass-Gathering Events: An Integrative Literature Review.
AB  - BACKGROUND: There is a growing body of literature relating to mass-gathering
      events. A common thread amongst this literature, particularly the literature
      relating to music festivals, is the incidence of patients presenting with
      substance and/or alcohol intoxication. However, the impact of alcohol and/or
      drugs on the provision of in-event health care services has not been explored in
      detail.AimThe goal of this review was to develop an understanding of the impact
      of alcohol and/or drugs on in-event health care services at mass-gathering
      events. METHOD: This paper used integrative review as a methodology. The articles
      included in this literature review were sourced by searching databases inclusive
      of Medline (Ovid; US National Library of Medicine, National Institutes of Health;
      Bethesda, Maryland USA), Scopus (Elsevier; Amsterdam, Netherlands), PsycINFO
      (Ovid; American Psychological Association; Washington DC, USA), and Pub Med
      (National Center for Biotechnology Information, National Institutes of Health;
      Bethesda, Maryland USA). Identified manuscripts that met the inclusion criteria
      were thematically analyzed. RESULTS: In total, 12 manuscripts met the inclusion
      criteria for this review. A thematic analysis of these manuscripts identified
      three main themes: (i) predictive factors, (ii) patient presentation rates, and
      (iii) levels of care. CONCLUSION: Substance use and/or intoxication can place a
      strain on in-event medical services at mass-gathering events. Of the various
      types of mass-gathering events, music festivals appear to be the most affected by
      substance use and intoxication. BullockM, RanseJ, HuttonA. Impact of patients
      presenting with alcohol and/or drug intoxication on in-event health care services
      at mass-gathering events: an integrative literature review. Prehosp Disaster Med.
      2018;33(5):539-542.

PMID- 30208985
TI  - A systematic review of effectiveness and cost-effectiveness of school-based
      identification of children and young people at risk of, or currently experiencing
      mental health difficulties.
AB  - BACKGROUND: Although school-based programmes for the identification of children
      and young people (CYP) with mental health difficulties (MHD) have the potential
      to improve short- and long-term outcomes across a range of mental disorders, the
      evidence-base on the effectiveness of these programmes is underdeveloped. In this
      systematic review, we sought to identify and synthesise evidence on the
      effectiveness and cost-effectiveness of school-based methods to identify students
      experiencing MHD, as measured by accurate identification, referral rates, and
      service uptake. METHOD: Electronic bibliographic databases: MEDLINE, Embase,
      PsycINFO, ERIC, British Education Index and ASSIA were searched. Comparative
      studies were included if they assessed the effectiveness or cost-effectiveness of
      strategies to identify students in formal education aged 3-18 years with MHD,
      presenting symptoms of mental ill health, or exposed to psychosocial risks that
      increase the likelihood of developing a MHD. RESULTS: We identified 27 studies
      describing 44 unique identification programmes. Only one study was a randomised
      controlled trial. Most studies evaluated the utility of universal screening
      programmes; where comparison of identification rates was made, the comparator
      test varied across studies. The heterogeneity of studies, the absence of
      randomised studies and poor outcome reporting make for a weak evidence-base that
      only generate tentative conclusions about the effectiveness of school-based
      identification programmes. CONCLUSIONS: Well-designed pragmatic trials that
      include the evaluation of cost-effectiveness and detailed process evaluations are
      necessary to establish the accuracy of different identification models, as well
      as their effectiveness in connecting students to appropriate support in real
      world settings.

PMID- 30208986
TI  - Physiologic Aspects of Pig Kidney Transplantation in Nonhuman Primates.
AB  - Xenotransplantation can provide a solution to the current shortage of human
      organs for patients with terminal renal failure. The increasing availability of
      genetically engineered pigs, effective immunosuppressive therapy, and
      antiinflammatory therapy help to protect pig tissues from the primate immune
      response and can correct molecular incompatibilities. Life-supporting pig kidney
      xenografts have survived in NHP for more than 6 mo in the absence of markers of
      consumptive coagulopathy. However, few reports have focused on the physiologic
      aspects of life-supporting pig kidney xenografts. We have reviewed the literature
      regarding pig kidney xenotransplantation in NHP. The available data indicate (1)
      normal serum creatinine, (2) normal serum electrolytes, except for a trend toward
      increased calcium levels and a transient rise in phosphate followed by a fall to
      slightly subnormal values, (3) minimal or modest proteinuria without
      hypoalbuminemia (suggesting that previous reports of proteinuria likely were due
      to a low-grade immune response rather than physiologic incompatibilities), (4)
      possible discrepancies between pig erythropoietin and the primate erythropoietin
      receptor, and (5) significant early increase in kidney graft size, which might
      result from persistent effects of pig growth hormone. Further study is required
      regarding identification and investigation of physiologic incompatibilities.
      However, current evidence suggests that, in the absence of an immune response, a
      transplanted pig kidney likely would satisfactorily support a human patient.

PMID- 30208987
TI  - Characterization of a Swine (Sus scrofa) Model of Oral Potassium Cyanide
      Intoxication.
AB  - Cyanide is a readily available and potentially lethal substance. Oral exposure
      can result in larger doses, compared with other routes. Currently, there are no
      antidotes specific for use in the treatment of oral cyanide poisoning, and
      studies cannot be done in humans. We report on a new large animal model of oral
      cyanide toxicity to evaluate potential antidotes. Six female swine (Sus scrofa;
      weight, 45 to 55 kg) were anesthetized, intubated, and instrumented. Animals
      received a KCN bolus of either 5 or 8 mg/kg delivered via orogastric tube. Time
      to apnea was recorded; parameters monitored included heart rate, respiratory
      rate, blood pressure, pulse oximetry, end-tidal CO2, arterial blood gasses, and
      lactate concentrations. The Welch t test was used to calculate confidence
      intervals, mean, and standard deviation, and a Kaplan-Meier survival curve was
      used to compare survival between the 2 groups. At baseline, all animals in both
      groups were similar. Animals in the 5-mg/kg group had a more rapid time to apnea
      (5.1 +/- 2.1 min), longer time to death (48.5 +/- 38.1 min), and a greater rate
      of survival than the 8-mg/kg group (apnea, 10.6 +/- 10.7 min; death, 26.1 +/- 5.8
      min). All animals displayed signs of toxicity (acidemia, hyperlactatemia,
      hypotension, apnea). We here report a large animal (swine) model of oral cyanide
      poisoning with dose-dependent effects in regard to time to death and survival
      rate. This model likely will be valuable for the development of medical
      countermeasures for oral cyanide poisoning.

PMID- 30208988
TI  - Outbreak of Opportunistic Ascending Pyelonephritis with Numerous Yeast after
      Experimental Humanization Surgery in NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ and NOD.Cg
      Rag1tm1Mom Il2rgtm1Wjl/SzJ Immunodeficient Mice.
AB  - Unexpected mortality occurred in a group of 12 NOD.Cg-NOD.Cg
      PrkdcscidIl2rgtm1Wjl/SzJ (NSG) and 12 NOD.Cg-Rag1tm1Mom Il2rgtm1Wjl/SzJ (NRG)
      immunodeficient mice. At 10 d after routine bone marrow-liver-thymus humanization
      surgery, 9 mice were found dead without observation of initiating clinical signs;
      1 d later (day 11), 3 additional mice showed signs of morbidity, including severe
      hunching, lateral recumbency, slow movement, shallow respiration, and decreased
      response to external stimulus. All remaining mice rapidly decompensated and were
      found dead or were euthanized within 4 d after the first death. Histopathology
      revealed severe ascending pyelonephritis with numerous yeast. Cultures in some
      mice were positive for Enterococcus faecalis or Staphylococcus xylosus, 2
      bacteria considered commensals in rodents. In addition, Candida albicans was
      cultured from some animals. Further investigation revealed that a restraining
      device used for tail vein injections was the likely fomite harboring Candida
      organisms. These findings indicate that ascending pyelonephritis, with Candida as
      the etiologic agent, can cause significant mortality in NSG and NRG
      immunodeficient mice.

PMID- 30208989
TI  - Evaluation of Infrared Thermography for Temperature Measurement in Adult Male
      NMRI Nude Mice.
AB  - Temperature monitoring during critical care provides important data required to
      guide treatment delivery. Body temperatureis an easily quantified clinical
      parameter that can yield much information concerning the health of an animal. In
      researchsettings, temperature has been adopted as a means to judge humane
      endpoints. Therefore, reliable, noninvasive, and inexpensivemethods for
      temperature monitoring are becoming a necessity in research laboratories. This
      study aimed to determinethe accuracy and agreement of using an infrared camera as
      an alternative method of temperature measurement in mice andto compare the
      accuracy of this noninvasive method with established subcutaneous,
      intraperitoneal, and rectal techniques.Measurement of body-surface temperature by
      using an infrared camera was compared with these 3 established methods inmale
      NMRI nude mice (n = 10; age, 10 mo); data were obtained 3 times daily over 14 d.
      Subcutaneous temperatures weremeasured remotely by using a previously implanted
      subcutaneous temperature transponder, after which temperature wasmeasured by
      using noncontact infrared thermometry and a rectal probe. Measurements from
      intraperitoneal data loggers wereobtained retrospectively. The data show that
      using an infrared camera provides a simple, reliable method for measuring
      bodytemperature in male NMRI nu/nu mice that minimizes handling and is minimally
      invasive. Whether infrared thermometry is a useful method for measuring body
      temperature in furred mice warrants further investigation.

PMID- 30208990
TI  - Effects of Laboratory Animal Science Training on Scientists' Attitudes and
      Practice in Egypt.
AB  - The implementation of principles and guidelines that govern the various areas of
      research in an educational institution isone of the key factors in international
      recognition of its research integrity and value. The privilege of conducting
      research using animal subjects requires adherence to international regulations
      and standards governing the humane care and use of laboratory animals. The IACUC
      at our university deemed it critical to have an animal care and use training
      program to raise researchers' understanding and knowledge. Our IACUC recently
      designed a training program in the principles of laboratory animal science and
      the ethical issues involved in animal use. The present study aimed to measure the
      effect of such training on scientists' attitudes and practice. During 4
      successive training courses, the participants (n = 100; 72% women and 28%
      men)were surveyed twice through self-administered questionnaire-before starting
      and after completing the course. Questions focused on ethical consideration for
      care and use of animals in research, ethical committees, international guidelines
      for humane care of animals, and 3Rs concepts and their interpretation. The
      results revealed that the scientists' knowledge and awareness increased
      effectively after the completion of the training courses. They understood the 3Rs
      concepts of replacement,reduction, and refinement; recognized the importance of
      standardization of animal handling on scientific results; and were able to
      distinguish between different ethical committees and their roles. Overall,
      training leads to standardization of animal care and use practices that are vital
      for the reproducibility of results fundamental to quality scientific research.

PMID- 30208991
TI  - Reference Intervals for Plasma Biochemical Variables by Point-of-Care Testing in
      Captive Black-tailed Prairie Dogs (Cynomys ludovicianus).
AB  - Black-tailed prairie dogs (Cynomys ludovicianus) are kept in zoological
      collections, maintained as companion pets, and aretested in field and laboratory
      settings. Biochemical analysis for routine health and research purposes can be
      performed byusing point-of-care (POC) testing; however, analyzer- and species
      specific reference intervals need to be determined. In this prospective study, 50
      captive-raised sexually intact prairie dogs (16 females, 34 males) underwent
      plasma biochemical analysisby using a veterinary POC biochemical analyzer. We
      used a manufacturer-predetermined profile of 14 analytes: albumin, ALP,ALT,
      amylase, BUN, calcium, creatinine, glucose, potassium, sodium, phosphorus, total
      bilirubin, total protein and globulin.A subset of 17 samples was tested
      concurrently for the same 14 analytes by using a reference laboratory analyzer,
      and wedetermined RI for the POC analyzer for these 14 biochemical analytes. Sex
      had a significant effect on albumin and creatininevalues, which were higher in
      females than males, and on ALT, which was lower in females. In addition, age had
      an effect on9 plasma analytes: juvenile animals had higher plasma concentrations
      of albumin, ALP, ALT, BUN, and glucose than adultanimals, whereas adults had
      higher concentrations of creatinine, sodium, total protein, and globulins. Only
      calcium and BUNhad acceptable analytical agreement between the POC and reference
      analyzers. The reference intervals determined in this study can aid clinicians
      and researchers performing POC plasma biochemical analysis in prairie dogs,
      providing that they consider potential analyzer-, sex-, and age-related effects.

PMID- 30208993
TI  - Notification that new names of prokaryotes, new combinations, and new taxonomic
      opinions have appeared in volume 68, part 6, of the IJSEM.

PMID- 30208992
TI  - Supernumerary Incisors in CB6F1 Mice Conditioned with Chemotherapy and Total Body
      Irradiation before Bone Marrow Transplantation.
AB  - Multiple adult female CB6F1 mice presented with supernumerary incisors after
      preconditioning with chemotherapy and total body irradiation for bone marrow
      transplantation (BMT). Mice received nonmyeloablative total body irradiation (3
      Gy) and either cyclophosphamide or bendamustine, followed by BMT and
      posttransplantation cyclophosphamide or bendamustine. Here we describe the
      clinical presentation, MUCT findings, and histopathologic evaluation of the
      affected mice. These analyses confirmed the gross diagnosis and revealed details
      of the abnormal tooth morphology. We surmise that the combination of total body
      irradiation and chemotherapy resulted in the abnormal formation of supernumerary
      incisors. Supernumerary teeth should be considered as a potential confounding
      factor in tracking weight loss after BMT. These conditions can be managed to
      allow animals to reach their intended scientific endpoint.

PMID- 30208994
TI  - A Comparison of Heterogeneous/Homogeneous Crystallization for Phosphate Recovery
      from Biosolids.
AB  - In this study, a fluidized bed reactor was used to compare heterogeneous and
      homogeneous crystallization for recovering magnesium ammonia phosphate (MAP) from
      the dewatering filtrate at a municipal water resource recovery facility.
      Investigating the factors affecting crystallization revealed that pH exerted a
      greater effect than the Mg/P molar ratio. The results of a heterogeneous
      crystallization experiment showed that removal efficiency of phosphate (RP%) and
      crystal efficiency of phosphate (CP%) were 68% and 66%, respectively, at a PO4-P
      concentration of 200 mg/L, pH of 8.0, and Mg/P molar ratio of 1.0 for 3 h. The
      reaction rate of heterogeneous crystallization was markedly higher than that of
      homogeneous crystallization. Those pellets produced through the heterogeneous
      crystallization exhibited a dense surface (particle size 0.5-1.0 mm; water
      content 8.7%). Through scanning electron microscopy (SEM), energy dispersive x
      ray spectroscopy (EDS), and X-ray diffraction (XRD) examination, the crystallized
      patterns of the needle-shaped pellets were identified as MgNH4PO4.6H2O.

PMID- 30208995
TI  - LED-Based Ultraviolet Oxidation of Pharmaceuticals: Effects of Wavelength and
      Intensity, pH, and TiO2 Loading.
AB  - The presence of pharmaceuticals in water resources has alarmed water and health
      authorities. This study evaluated ultraviolet-based oxidation as a means to
      decompose sulfamethoxazole, ibuprofen, and triclosan. In particular, the study
      evaluated using light emitting diodes (LEDs), the so-called ultraviolet LEDs (UV
      LEDs), as an alternative ultraviolet source to the problematic mercury lamps that
      are conventionally used in the decomposition of pharmaceuticals in water. The
      study explored various conditions of varying ultraviolet wavelength, irradiation
      intensity, reaction pH, and TiO2 loading. It compared the photolytic
      decomposition of the pharmaceuticals with their photocatalytic decomposition. The
      photolytic decomposition of the pharmaceuticals was solely determined by the
      relation between their ultraviolet absorption characteristics and the ultraviolet
      emission spectra of the LEDs. Reaction pH greatly affected both photolytic
      decomposition and photocatalytic decomposition. The presence of TiO2 in cases
      where significant photolysis was present inhibited the overall decomposition
      process. However, in all cases, photocatalysis showed better mineralization than
      photolysis.

PMID- 30208996
TI  - Nitrogen Removal and N2O Emission in Biochar-Sludge Subsurface Wastewater
      Infiltration Systems.
AB  - Nitrogen removal and N2O emission of biochar-sludge amended subsurface
      wastewater infiltration systems (SWISs) with/without intermittent aeration under
      different organic surface loading rates (OSLRs) were investigated. Under OSLR,
      between 8.5 and 54.6 g COD/(m2 d), average chemical oxygen demand (COD), <inline
      graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="00800
      ilm01.gif"/>, and total nitrogen (TN) removal rates decreased with OSLR
      increasing in non-aerated SWISs amended with/without biochar-sludge; increasing
      OSLR hardly affected COD and <inline-graphic
      xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="00800-ilm12.gif"/> removal
      in biochar-sludge amended SWIS with intermittent aeration; N2O emission rate
      decreased with influent OSLR increasing in the SWISs. Biochar-sludge amended SWIS
      with intermittent aeration obtained higher removal rates for COD (94.9 to 95.5%),
      <inline-graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="00800
      ilm23.gif"/> (90.5 to 93.7%), TN (86.5 to 89.9%) and lower N2O emission rates
      [13.4 to 14.7 mg/(m2 d)] under high influent OSLR of 36.2 and 54.6 g COD/(m2 d)
      were compared with non-aerated SWISs with/without biochar-sludge. Furthermore,
      the abundances of amoA, nxrA, napA, narG, nirS, nirK, qnorB, and nosZ genes
      involved in nitrogen removal were enhanced under high influent OSLR in biochar
      sludge amended SWIS with intermittent aeration.

PMID- 30208997
TI  - Photocatalytic Degradation of Methylene Blue Dye Using Silica Oxide Nanoparticles
      as a Catalyst.
AB  - The present research deals with the development a fast and low-cost method for
      removing color dye from water using nanosized semiconductors SiO2 as
      photocatalyst. The studies of kinetic photocatalytic degradation were carried out
      on an aqueous solution of soluble methylene blue dye, which contained SiO2
      nanoparticles and under an ultraviolet light source. Different parameters
      affecting the process have been studied: catalyst concentration, dye
      concentration, temperature, and pH of solution. The color variation was detected
      at three absorption bands (662, 293, and 243 nm). It was found that the dye
      completely degraded in 90 s, using 10 g/L SiO2 nanoparticles at 25  degrees C and
      pH 1.5 and 11.0. The adsorption of the dye well-fitted pseudo-second-order
      kinetic models. The Langmuir-Hinshelwood model was acquired to analyze the
      photocatalytic degradation process. A possible molecular mechanism for
      photocatalytic degradation of the dye by SiO2 nanoparticles is also given.

PMID- 30208998
TI  - Estimation of the Unbiodegradable Fraction of Thickened Waste Activated Sludge.
AB  - The study investigated the unbiodegradable fraction of particulate chemical
      oxygen demand (PCOD) in thickened waste activated sludge (TWAS) using
      semicontinuous-flow completely-mixed anaerobic digesters. A laboratory-scale
      semicontinuous stirred tank reactor was used to investigate TWAS anaerobic
      biodegradability at hydraulic retention time of 16.7 d to 33.3 d and organic
      loading rate (OLR) of 1.21 kg COD/m3*d to 3.47 kg COD/m3*d. The COD and volatile
      suspended solids (VSS) removal for TWAS were 37% to 44% and 39% to 42% at an OLR
      of 1.27 and 3.47 kg COD/m3*d, respectively. Using a biomass yield (<inline
      graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="00819
      ilm01.gif"/>) of 0.29 g COD biomass/g COD substrate, decay rate (<inline-graphic
      xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="00819-ilm02.gif"/>of 0.015
      d-1; and a solids retention time (SRT) of 16.7 d; two linear fits correlating the
      difference between effluent biomass; and effluent particulate COD with influent
      total COD, the unbiodegradable fractions of PCOD and VSS were estimated from the
      slopes of the linear fits to be in the range of 0.26 to 0.28.

PMID- 30208999
TI  - Phosphorus Recovery by Methods Beyond Struvite Precipitation.
AB  - Unintentional phosphate precipitation at water resource recovery facilities
      (WRRFs) causes operation and maintenance challenges. With global phosphorus (P)
      scarcity looming and receiving water eutrophication caused by excess discharges
      of P, intentional P recovery at WRRFs has been gaining traction. To date,
      struvite recovery as slow release fertilizer has been the focus of P recovery.
      However, struvite recovery is not always the most cost-effective approach,
      especially when phosphate fertilizers cost considerably less than the cost to
      recover struvite as fertilizer. The aim of this state-of-an-art review paper is
      to discuss P recovery as calcium phosphate, which could be a fertilizer feedstock
      and incurs less chemical costs to produce. Calcium phosphate also offers broader
      applications for other industrial uses beyond fertilizers since the composition
      is close to mined phosphate rock. A strategic approach for a regional reclaimed
      phosphate reserve is proposed to secure the most economical future supply of P.

PMID- 30209001
TI  - List of new names and new combinations previously effectively, but not validly,
      published.

PMID- 30209000
TI  - Characterization of Wastewater in Two U.S. Cattle Slaughterhouses.
AB  - Recent changes related to antimicrobial intervention technologies and reduction
      in product loss have affected cattle slaughterhouse wastewater streams. In this
      study, wastewater samples were collected from two cattle slaughterhouses located
      in the Midwest of the United States, focusing on the overall wastewater,
      antimicrobial interventions, and viscera and offal processing. The wastewater
      concentrations were affected by the water use, dilution, processes, and
      wastewater pretreatment that occurs within the slaughterhouse. Even though there
      were differences in the wastewater concentrations, the overall wastewater loads
      for both slaughterhouses were similar. The overall mean total solids (TS),
      volatile solids (VS), 5-day biological chemical demand (BOD5), and chemical
      oxygen demand (COD) wastewater loads for the two slaughterhouses were 16.8, 10.0,
      4.7, and 12.5 kg/1000 kg live weight killed, respectively. Wastewater streams
      from antimicrobial interventions have low pH and are potential sources of shock
      loadings. Wastewater from viscera and offal processing has high nutrient
      concentration; therefore, any improvement in this process could enhance the
      sustainability the industry.

PMID- 30209003
TI  - Aggregation recovers developmental plasticity in mouse polyploid embryos.
AB  - Tetraploid embryos normally develop into blastocysts and embryonic stem cells can
      be established from tetraploid blastocysts in mice. Thus, polyploidisation does
      not seem to be so harmful during preimplantation development. However, the
      mechanisms by which early mammalian development accepts polyploidisation are
      poorly understood. In this study, we aimed to elucidate the effect of
      polyploidisation on early mammalian development and to further comprehend its
      tolerance using hyperpolyploid embryos produced by repetitive whole genome
      duplication. We successfully established several types of polyploid embryos
      (tetraploid, octaploid and hexadecaploid) and studied their developmental
      potential in vitro. We demonstrated that all types of these polyploid embryos
      maintained the ability to develop to the blastocyst stage, which implies that
      mammalian cells might have basic cellular functions in implanted embryos, despite
      polyploidisation. However, the inner cell mass was absent in hexadecaploid
      blastocysts. To complement the total number of cells in blastocysts, a fused
      hexadecaploid embryo was produced by aggregating several hexadecaploid embryos.
      The results indicated that the fused hexadecaploid embryo finally recovered
      pluripotent cells in the blastocyst. Thus, our findings suggest that early
      mammalian embryos may have the tolerance and higher plasticity to adapt to
      hyperpolyploidisation for blastocyst formation, despite intense alteration of the
      genome volume.

PMID- 30209002
TI  - Everolimus, lutetium-177 DOTATATE and sunitinib for advanced, unresectable or
      metastatic neuroendocrine tumours with disease progression: a systematic review
      and cost-effectiveness analysis.
AB  - BACKGROUND: Neuroendocrine tumours (NETs) are a group of heterogeneous cancers
      that develop in cells in the diffuse neuroendocrine system. OBJECTIVES: To
      estimate the clinical effectiveness of three interventions [everolimus
      (Afinitor(r); Novartis International AG, Basel, Switzerland), lutetium-177
      DOTATATE (177Lu-DOTATATE) (Lutathera(r); Imaging Equipment Ltd, Radstock, UK) and
      sunitinib (Sutent(r); Pfizer Inc., New York, NY, USA)] for treating unresectable
      or metastatic NETs with disease progression and establish the cost-effectiveness
      of these interventions. DATA SOURCES: The following databases were searched from
      inception to May 2016: MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations,
      MEDLINE Daily, Epub Ahead of Print, EMBASE, Cochrane Central Register of
      Controlled Trials and Web of Science. REVIEW METHODS: We systematically reviewed
      the clinical effectiveness and cost-effectiveness literature on everolimus, 177Lu
      DOTATATE and sunitinib for treating advanced, unresectable or metastatic
      progressive NETs. The following NET locations were considered separately:
      pancreas, gastrointestinal (GI) tract and lung, and GI tract (midgut only). We
      wrote a survival partition cohort-based economic evaluation in Microsoft Excel(r)
      2013 (Microsoft Corporation, Redmond, WA, USA) from the UK NHS and Personal
      Social Services perspective. This comprised three health states: (1) progression
      free survival (PFS), (2) progressed disease and (3) death. RESULTS: Three
      randomised controlled trials (RCTs), RADIANT-3 [RAD001 in Advanced Neuroendocrine
      Tumors, Third Trial; pancreatic NETs (pNETs): everolimus vs. best supportive care
      (BSC)], A6181111 (pNETs: sunitinib vs. BSC) and RADIANT-4 (RAD001 in Advanced
      Neuroendocrine Tumors, Fourth Trial; GI and lung NETs: everolimus vs. BSC), met
      the inclusion criteria for the clinical effectiveness systematic review. The risk
      of bias was low. Although the NETTER-1 (Neuroendocrine Tumors Therapy) RCT, of
      177Lu-DOTATATE plus 30 mg of octreotide (Sandostatin(r), Novartis) compared with
      60 mg of octreotide, was excluded from the review, we nonetheless present the
      results of this trial, as it informs our estimate of the cost-effectiveness of
      177Lu-DOTATATE. The pNETs trials consistently found that the interventions
      improved PFS and overall survival (OS) compared with BSC. Our indirect comparison
      found no significant difference in PFS between everolimus and sunitinib.
      Estimates of OS gain were confounded because of high rates of treatment
      switching. After adjustment, our indirect comparison suggested a lower, but non
      significant, hazard of death for sunitinib compared with everolimus. In GI and
      lung NETs, everolimus significantly improved PFS compared with BSC and showed a
      non-significant trend towards improved OS compared with BSC. Adverse events were
      more commonly reported following treatment with targeted interventions than after
      treatment with BSC. In the base case for pNETs, assuming list prices, we
      estimated incremental cost-effectiveness ratios (ICERs) for everolimus compared
      with BSC of L45,493 per quality-adjusted life-year (QALY) and for sunitinib
      compared with BSC of L20,717 per QALY. These ICERs increased substantially
      without the adjustment for treatment switching. For GI and lung NETs, we
      estimated an ICER for everolimus compared with BSC of L44,557 per QALY. For GI
      (midgut) NETs, the ICERs were L199,233 per QALY for everolimus compared with BSC
      and L62,158 per QALY for a scenario analysis comparing 177Lu-DOTATATE with BSC.
      We judge that no treatment meets the National Institute for Health and Care
      Excellence's (NICE) end-of-life criteria, although we cannot rule out that
      sunitinib in the A6181111 trial does. LIMITATIONS: A RCT with included
      comparators was not identified for 177Lu-DOTATATE. The indirect treatment
      comparison that our economic analysis was based on was of a simple Bucher type,
      unadjusted for any differences in the baseline characteristics across the two
      trials. CONCLUSIONS: Given NICE's current stated range of L20,000-30,000 per QALY
      for the cost-effectiveness threshold, based on list prices, only sunitinib might
      be considered good value for money in England and Wales. FUTURE WORK: Further
      analysis of individual patient data from RADIANT-3 would allow assessment of the
      robustness of our findings. The data were not made available to us by the company
      sponsoring the trial. STUDY REGISTRATION: This study is registered as PROSPERO
      CRD42016041303. FUNDING: The National Institute for Health Research Health
      Technology Assessment programme.

PMID- 30209004
TI  - Melatonin reduces cAMP-stimulated capacitation of ram spermatozoa.
AB  - The presence of melatonin receptors on the surface of ram spermatozoa has led to
      speculation about melatonin having a role in sperm functionality. The aim of this
      study was to elucidate the mechanism through which melatonin regulates ram sperm
      capacitation induced by a cocktail containing cAMP-elevating agents. Cocktail
      samples capacitated in the presence of 1 uM melatonin showed lower percentages of
      capacitated spermatozoa (chlortetracycline staining; P < 0.001) together with a
      decrease in protein tyrosine phosphorylation (P < 0.01) and lower levels of
      reactive oxygen species (ROS) and cAMP (P < 0.05) compared with cocktail samples
      without the hormone. Determination of kinematic parameters, together with
      principal component and cluster analyses, allowed us to define four sperm
      subpopulations (SP). After 3 h of incubation with cAMP-elevating agents, the
      percentages of spermatozoa belonging to SP1 (high straightness) and SP4 (less
      vigorous spermatozoa with non-linear motility) increased while SP2 and SP3 (rapid
      spermatozoa starting hyperactivation or already hyperactivated) decreased
      compared with the control sample. The presence of melatonin at 100 pM and 10 nM
      restored these subpopulations to values closer to those found in the control
      sample. These results indicate that melatonin at micromolar concentrations
      modulates ram sperm capacitation induced by cAMP-elevating agents, reducing ROS
      and cAMP levels, whereas at lower concentrations melatonin modifies motile sperm
      subpopulations. These findings warrant further studies on the potential use of
      melatonin for controlling capacitation in artificial insemination procedures.

PMID- 30209005
TI  - Daunorubicin, a topoisomerase II poison, suppresses viral production of hepatitis
      B virus by inducing cGAS-dependent innate immune response.
AB  - Hepatitis B virus (HBV) causes hepatic diseases such as chronic hepatitis, liver
      cirrhosis, and hepatocellular carcinoma. These diseases are closely associated
      with persistent HBV infection. To prevent the progression of hepatic diseases, it
      is thus important to suppress persistent HBV infection. Daunorubicin (DNR), a
      topoisomerase II (Top II) poison, is a clinically used anticancer agent with a
      wide spectrum of activity against malignancies. DNR was recently reported to
      cause DNA damage-dependent interferon (IFN)-beta induction through exogenous
      cyclic GMP-AMP synthetase (cGAS) and subsequently to suppress Ebola virus
      replication. In the present study, we demonstrated that DNR caused the inhibition
      of cell proliferation, but not cell death, through the DNA damage response in
      immortalized human hepatocyte NKNT-3/NTCP cells. Interestingly, DNR triggered the
      endogenous cGAS-dependent innate immune response and subsequently suppressed
      viral production of HBV in NKNT-3/NTCP cells. Top II poisons may be anti-HBV drug
      candidates.

PMID- 30209006
TI  - Diagnostic accuracy of a rapid telemedicine encounter in the Emergency
      Department.
AB  - OBJECTIVES: Emergency Department crowding is an increasing problem, leading to
      treatment delays and higher risk of mortality. Our institution recently
      implemented a telemedicine physician intake ("tele-intake") process as a
      mitigating front-end strategy. Previous studies have focused on ED throughput
      metrics such as door to disposition; our work aimed to specifically assess the
      tele-intake model for clinical accuracy. METHODS: We retrospectively reviewed ED
      visits at a high acuity, tertiary care academic hospital before and after tele
      intake implementation. We defined the primary outcome as the degree of additional
      laboratory, imaging, and medication orders placed by the subsequent ED provider.
      Our secondary outcomes were the cancellation rate of intake orders and the
      percentage of encounters where no additional second provider orders were
      necessary. RESULTS: For in-person and tele-intake physician encounters between
      September 2015 and February 2017, most labs and diagnostic radiology studies, and
      approximately half of CT, ultrasound, and pharmacy orders were initiated by the
      intake physician. We found no significant difference for our primary outcome (p =
      0.2449). For both tele-intake and in-person encounters, <1% of orders were
      cancelled by the second provider. Additionally, 30.8% of in-person and 31.5% of
      telemedicine patient encounters required no additional orders to make a
      disposition decision. DISCUSSION: This novel analysis of an innovative patient
      care model suggests that the benefits of tele-intake as a replacement for in
      person physician directed intake are not at the cost of over or under utilization
      of diagnostic testing or interventions.

PMID- 30209007
TI  - Pharmacist impact on sepsis bundle compliance through participation on an
      emergency department sepsis alert team.

PMID- 30209009
TI  - The Road Map for Proton Therapy.

PMID- 30209008
TI  - Liver Ultrasound Elastography: An Update to the World Federation for Ultrasound
      in Medicine and Biology Guidelines and Recommendations.
AB  - The World Federation for Ultrasound in Medicine and Biology has produced these
      guidelines for the use of elastography techniques in liver diseases. For each
      available technique, the reproducibility, results and limitations are analyzed,
      and recommendations are given. This set of guidelines updates the first version,
      published in 2015. Since the prior guidelines, there have been several advances
      in technology. The recommendations are based on the international published
      literature, and the strength of each recommendation is judged according to the
      Oxford Centre for Evidence-Based Medicine. The document has a clinical
      perspective and is aimed at assessing the usefulness of elastography in the
      management of liver diseases.

PMID- 30209010
TI  - The Potential Value of MRI in External-Beam Radiotherapy for Cervical Cancer.
AB  - The reference standard treatment for cervical cancer is concurrent
      chemoradiotherapy followed by magnetic resonance imaging (MRI)-guided
      brachytherapy. Improvements in brachytherapy have increased local control rates,
      but late toxicity remains high with rates of 11% grade >=3. The primary clinical
      target volume (CTV) for external-beam radiotherapy includes the cervix and
      uterus, which can show significant inter-fraction motion. This means that
      generous margins are required to cover the primary CTV, increasing the radiation
      dose to organs at risk and, therefore, toxicity. A number of image-guided
      radiotherapy techniques (IGRT) have been developed, but motion can be random and
      difficult to predict prior to treatment. In light of the development of
      integrated MRI linear accelerators, this review discusses the potential value of
      MRI in external-beam radiotherapy. Current solutions for managing pelvic organ
      motion are reviewed, including the potential for online adaptive radiotherapy.
      The impacts of the use of MRI in tumour delineation and in the delivery of
      stereotactic ablative body radiotherapy (SABR) are highlighted. The potential
      role and challenges of using multi parametric MRI to guide radiotherapy are also
      discussed.

PMID- 30209012
TI  - Optimizing use of existing prenatal genetic tests: Screening and diagnostic
      testing for aneuploidy.
AB  - Screening and diagnostic testing for detection of fetal aneuploidy has been an
      integral part of prenatal care for over three decades. The recent introduction of
      new technologies, such as cell free DNA (cfDNA) screening and preimplantation
      genetic screening, has created increased complexity for obstetrical care
      providers. Inconsistencies among the professional society recommendations have
      caused confusion and disparities in practice. As we work to responsibly
      incorporate new technologies, clear guidelines with consensus among relevant
      professional societies are needed. In January of 2017, a workshop was convened
      during the Society for Maternal-Fetal Medicine Pregnancy Meeting. Representatives
      from many stakeholder groups were present with the goal to develop a framework
      for introduction of new genetic tests into clinical practice. This paper provides
      consensus recommendations from this workshop on the use of existing prenatal
      screening and diagnostic testing for aneuploidy.

PMID- 30209011
TI  - Macroecology to Unite All Life, Large and Small.
AB  - Macroecology is the study of the mechanisms underlying general patterns of
      ecology across scales. Research in microbial ecology and macroecology have long
      been detached. Here, we argue that it is time to bridge the gap, as they share a
      common currency of species and individuals, and a common goal of understanding
      the causes and consequences of changes in biodiversity. Microbial ecology and
      macroecology will mutually benefit from a unified research agenda and shared
      datasets that span the entirety of the biodiversity of life and the geographic
      expanse of the Earth.

PMID- 30209013
TI  - The cerebellar "tilted telephone receiver sign" enables prenatal diagnosis of
      PHACES syndrome.
AB  - OBJECTIVES: To describe a unique posterior fossa neuroimaging characteristic of
      prenatal PHACES syndrome (PS): unilateral cerebellar hypoplasia (UCH) and
      ipsilateral posterior fossa (PF) cyst communicating with an asymmetrically
      distended 4th ventricle. METHODS: The registries of seven prenatal diagnosis
      centers were searched for cases with PF findings and a postnatal diagnosis of PS.
      All records were evaluated for ultrasound and MRI findings and the postnatal
      outcome. PS was diagnosed after birth according to the consensus statement on
      diagnostic criteria for PS from 2009. The imaging findings of the PS fetuses were
      compared to a group of consecutive cases with fetal UCH, whose postnatal
      diagnosis was not PS. RESULTS: The PS group included 10 fetuses. All were
      referred due to UCH accompanied by an ipsilateral retrocerebellar cyst. All
      pregnancies resulted in livebirths, all newborns had a large segmental facial
      hemangioma. In all PS fetuses the affected cerebellar hemisphere was upwardly
      displaced by an ipsilateral PF cyst communicating with an asymmetrically
      distended 4th ventricle. An upwardly rotated and deviated vermis merged with the
      contralateral cerebellar peduncles forming an elongated oblique connection
      between the cerebellar hemispheres, resulting in a unique cerebellar shape, "a
      tilted telephone receiver sign" (TTRS), on the coronal plane through the upper
      vermis.The non-PS group included 11 fetuses with UCH: clastic cerebellar lesions
      (8) and a unilateral PF arachnoid cyst (3). The TTRS was not depicted in any of
      them (p < 0.0005). CONCLUSIONS: The cerebellar TTRS is a specific fetal imaging
      feature of PHACES syndrome enabling its prenatal diagnosis.

PMID- 30209014
TI  - No differences in patient-reported outcomes between medial pivot insert and
      symmetrical insert in total knee arthroplasty: A randomized analysis.
AB  - BACKGROUND: Although total knee arthroplasty (TKA) using a medial pivot insert
      reportedly improves kinematics compared with a symmetrical insert, improvements
      in patient-reported outcomes have not yet been reported. The aim of this study
      was to determine whether insert designs influenced patient-reported outcomes.
      METHODS: Seventy TKAs for osteoarthritis were randomly allocated to a symmetrical
      dish insert (SD group: 35 knees) or medial pivot insert (MP group: 35 knees).
      Thirty-two of the SD group (74.4 +/- 6.6 years old) and 33 of the MP group (73.8
      +/- 6.0 years old) completed the two-year follow-up. The knee range of motion
      (ROM) and 2011 Knee Society score (2011KSS) were analyzed pre-operatively and
      postoperatively. RESULTS: There was no difference in pre-operative ROM or 2011KSS
      (Symptom: 7.3 +/- 5.9 in SD group, 8.4 +/- 5.4 in MP group, P = 0.432;
      Satisfaction: 12.6 +/- 6.9 in SD group, 11.8 +/- 5.9 in MP group, P = 0.581;
      Activity: 35.8 +/- 18.1 in SD group, 35.2 +/- 18.6 in MP group, P = 0.883). At
      two years, although both group showed good improvement, there were no differences
      in ROM or 2011KSS (Symptom: 19.3 +/- 5.0 in SD group, 18.3 +/- 4.1 in MP group, P
      = 0.351; Satisfaction: 24.0 +/- 7.6 in SD group, 22.9 +/- 7.9 in MP group, P =
      0.548; Activity: 60.3 +/- 14.8 in SD group, 54.3 +/- 17.3 in MP group, P =
      0.137). CONCLUSIONS: The medial pivot insert was not superior to the symmetrical
      insert in patient-reported outcomes at two years after TKA.

PMID- 30209016
TI  - Issues in preclinical radiopharmaceutical research: Significance, relevance and
      reproducibility.

PMID- 30209017
TI  - Risk-stratified outcomes with initial combination therapy in pulmonary arterial
      hypertension: Application of the REVEAL risk score.
AB  - BACKGROUND: The multinational AMBITION study demonstrated a 50% risk reduction in
      time to first clinical failure event (TtCF, a composite of death, hospitalization
      for worsening pulmonary arterial hypertension [PAH], disease progression, or
      unsatisfactory long-term clinical response) in treatment-naive Functional Class
      II and III PAH patients initiated on combination therapy (ambrisentan and
      tadalafil) vs monotherapy. A post-hoc analysis of AMBITION data by risk
      stratification, as determined by baseline REVEAL risk score, was undertaken to
      better assess the impact of combination therapy. METHODS: Patients were
      randomized 2:1:1 to initial combination therapy with ambrisentan 10 mg plus
      tadalafil 40 mg vs either drug plus placebo, respectively. Baseline REVEAL risk
      scores in the 605 patients were grouped by low, intermediate, or high risk.
      Adjudicated outcomes (TtCF and post-hoc composite end-point of time to first PAH
      hospitalization or death) were assessed by risk group and treatment assignment.
      RESULTS: At baseline, risk groups were similarly represented across treatment
      assignments as low (16%), intermediate (46%), and high (38%) risk. Greater risk
      was associated with worse outcome. At each level of risk, patients on combination
      therapy had significantly fewer TtCF or PAH hospitalization/death events relative
      to those on monotherapy, and discontinuations due to adverse events were not
      higher on combination therapy. CONCLUSIONS: This post-hoc analysis comparing
      outcomes by REVEAL risk group has shown that, at all levels of risk, patients
      enrolled in AMBITION receiving initial combination therapy have superior outcomes
      and, even in those assessed as low risk, initial combination therapy was
      clinically beneficial.

PMID- 30209015
TI  - 19q12 amplified and non-amplified subsets of high grade serous ovarian cancer
      with overexpression of cyclin E1 differ in their molecular drivers and clinical
      outcomes.
AB  - OBJECTIVES: Readily apparent cyclin E1 expression occurs in 50% of HGSOC, but
      only half are linked to 19q12 locus amplification. The amplified/cyclin E1hi
      subset has intact BRCA1/2, unfavorable outcome, and is potentially
      therapeutically targetable. We studied whether non-amplified/cyclin E1hi HGSOC
      has similar characteristics. We also assessed the expression of cyclin E1
      degradation-associated proteins, FBXW7 and USP28, as potential drivers of high
      cyclin E1 expression in both subsets. METHODS: 262 HGSOC cases were analyzed by
      in situ hybridization for 19q12 locus amplification and immunohistochemistry for
      cyclin E1, URI1 (another protein encoded by the 19q12 locus), FBXW7 and USP28
      expression. Tumors were classified by 19q12 amplification status and correlated
      to cyclin E1 and URI1 expression, BRCA1/2 germline mutation, FBXW7 and USP28
      expression, and clinical outcomes. Additionally, we assessed the relative genomic
      instability of amplified/cyclin E1hi and non-amplified/cyclin E1hi groups of
      HGSOC datasets from The Cancer Genome Atlas. RESULTS: Of the 82 cyclin E1hi
      cases, 43 (52%) were amplified and 39 (48%) were non-amplified. Unlike amplified
      tumors, non-amplified/cyclin E1hi tumor status was not mutually exclusive with
      gBRCA1/2 mutation. The non-amplified/cyclin E1hi group had significantly
      increased USP28, while the amplified/cyclin E1hi cancers had significantly lower
      FBXW7 expression consistent with a role for both in stabilizing cyclin E1.
      Notably, only the amplified/cyclin E1hi subset was associated with genomic
      instability and had a worse outcome than non-amplified/cyclin E1hi group.
      CONCLUSIONS: Amplified/cyclin E1hi and non-amplified/cyclin E1hi tumors have
      different pathological and biological characteristics and clinical outcomes
      indicating that they are separate subsets of cyclin E1hi HGSOC.

PMID- 30209018
TI  - tRNA-halves are prognostic biomarkers for patients with prostate cancer.
AB  - OBJECTIVE: Noncoding RNAs play an important role in carcinogenesis; a number of
      tRNA-halves are expressed in response to androgen stimulation and are involved in
      prostate cancer (CaP) initiation and progression. In this study, we evaluated the
      expression profile of androgen-dependent tRNA-halves in CaP. MATERIALS AND
      METHODS: Total RNA was isolated from formalin-fixed paraffin-embedded 58 CaP, and
      25 benign prostate hyperplasia tissues. We also studied the expression in serum
      from 49 localized and 21 metastatic castration-resistant CaP samples. The
      ligation of a RNA adaptor molecule to the tRNA-halves allowed the specific
      amplification of 3'/5'-tRNA-halves using quantitative TaqMan reverse
      transcription polymerase chain reaction. The expression levels were correlated
      with clinicopathological parameters as well as prostate-specific antigen
      recurrence free survival. RESULTS: 5'-tRNA-Asp-GUC-half and 3'-tRNA-Asp-GUC-half
      were up-regulated in CaP tissues compared with benign prostate hyperplasia
      tissues. An increased expression level of all the 5 candidate tRNA-halves was
      associated with adverse clinicopathological parameters (pT-stage, pN-stage,
      prostate-specific antigen, International Society of Urological Pathology /ISUP
      grade) and a shorter time to biochemical relapse. In serum, 5'-tRNA-Glu-CUC-half
      was circulating at a higher level in metastatic castration-resistant CaP patients
      compared to patients with localized CaP. CONCLUSIONS: The androgen-dependent tRNA
      halves can potentially act as biomarkers to monitor and predict the progression
      of CaP.

PMID- 30209020
TI  - When is "brainstem death" brain death? The case for ancillary testing in primary
      infratentorial brain lesion.
AB  - The widely accepted concept of brain death (BD) comprises the demonstration of
      irreversible coma in combination with the loss of brainstem reflexes and
      irreversible apnea. In some countries the combined clinical finding of coma,
      apnea, and loss of all tested brainstem reflexes ("brainstem death") is
      sufficient for diagnosing BD irrespective of the primary location of brain
      lesion. The present article aims to substantiate the need for ancillary testing
      in patients with primary infratentorial brain lesions. Anatomically, the
      "brainstem-death" syndrome can theoretically occur without relevant lesion of the
      mesopontine tegmental reticular formation (MPT-RF). Thus, a brainstem lesion may
      cause an apneic total locked-in syndrome, a rare syndrome with preserved
      capability for consciousness, mimicking "brainstem death". Findings in animals
      and humans have shown that alpha- or alpha/theta- EEG patterns in case of
      isolated brainstem lesion indicate intactness of relevant parts of the MPT-RF. In
      such patients the presence of irreversible coma has to be doubted, and the
      potential capacity for some degree of consciousness cannot be excluded as long as
      the EEG activity persists. Consequently the demonstration of either ancillary
      finding, electro-cortical inactivity or, preferably, cerebral circulatory arrest,
      is mandatory for diagnosing BD in patients with a primary infratentorial brain
      lesion.

PMID- 30209019
TI  - Inflammation, adiposity, and progression of arterial stiffness in adolescents
      with type 1 diabetes: The SEARCH CVD Study.
AB  - AIMS: We examined the association between inflammation and progression of
      arterial stiffness in a population of youth with type 1 diabetes (T1D). METHODS:
      A total of 287 youth with T1D (median age 13 years) from SEARCH CVD, an ancillary
      study to the SEARCH for Diabetes in Youth, were included. Markers of inflammation
      (CRP, IL-6, fibrinogen, leptin, and adiponectin) and measures of pulse wave
      velocity (PWV) of the arm (PWV-R), trunk (PWV-T), and lower extremity (PWV-LE)
      were measured at baseline. Measures of PWV were repeated approximately five years
      later. RESULTS: PWV-R (0.50 m/s), PWV-T (0.65 m/s), and PWV-LE (1.0 m/s)
      significantly increased over the follow-up (p < 0.001 for each). A significant
      interaction was found between waist circumference and fibrinogen (p = 0.036) on
      the progression of PWV-T, suggesting that fibrinogen is more strongly associated
      with PWV progression in lean participants. CONCLUSIONS: Improved understanding of
      adiposity, inflammation, and functional changes in the vascular system in
      patients with T1D is crucial.

PMID- 30209021
TI  - Identification of generator criticality and transient instability by supervising
      real-time rotor angle trajectories employing RBFNN.
AB  - Identification of transient stability state in real-time and maintaining
      stability through preventive control technology are challenging tasks for a large
      power system while integrating deregulation constraints. Widely employment of the
      phasor measurement units (PMUs) in a power system and development of wide area
      management systems (WAMS) give relaxation to monitoring, measurement and control
      hurdles. This paper focuses on two research objectives; the first is transient
      stability assessment (TSA) and second is selection of the appropriate member for
      the control operation in unstable operating scenario. A model based on the
      artificial machine learning and PMU data is constructed for achieving both the
      objectives. This model works through prompt TSA status with radial basis function
      neural network (RBFNN) and validates it with PMU data to determine the
      criticality level of the generators. To reduce the complexity of the model a
      transient stability index (TSI) is proposed in this paper. A RBFNN is used to
      determine the transient stability aspects like stability status of system,
      coherent group and criticality rank of generator and preventive control action,
      following a large perturbation. PMUs measure post-fault rotor angle values and
      these are used as input for training RBFNN. The proposed approach is demonstrated
      on the IEEE 10-generator 39-bus, 16-generator 68-bus and 50-generator 145-bus
      test power systems successfully and the effectiveness of the approaches is
      discussed.

PMID- 30209022
TI  - Pulmonary function in repaired congenital heart disease: Our attention must reach
      beyond the mended heart.

PMID- 30209023
TI  - A Wood Biology Agenda to Support Global Vegetation Modelling.
AB  - Realistic forecasting of forest responses to climate change critically depends on
      key advancements in global vegetation modelling. Compared with traditional 'big
      leaf' models that simulate forest stands, 'next-generation' vegetation models aim
      to track carbon-, light-, water-, and nutrient-limited growth of individual
      trees. Wood biology can play an important role in delivering the required
      knowledge at tissue-to-individual levels, at minute-to-century scales and for
      model parameterization and benchmarking. We propose a wood biology research
      agenda that contributes to filling six knowledge gaps: sink versus source
      limitation, drivers of intra-annual growth, drought impacts, functional wood
      traits, dynamic biomass allocation, and nutrient cycling. Executing this agenda
      will expedite model development and increase the ability of models to forecast
      global change impact on forest dynamics.

PMID- 30209024
TI  - Efficacy of liposomal amphotericin B against four species of Candida biofilms in
      an experimental mouse model of intravascular catheter infection.
AB  - The formation of Candida biofilms on implanted medical devices is crucial to the
      development of infections and an important clinical problem because of elevated
      resistance to antifungals. The aim of this study was to compare the in vitro
      activity of liposomal amphotericin B (L-AMB) and micafungin (MCFG) against four
      species of Candida biofilms, and the efficacy of systemic plus lock therapy with
      L-AMB and MCFG in a Candida biofilm-associated catheter infection model. An XTT
      reduction assay was used to measure the metabolic activity of the biofilms to
      evaluation of in vitro antibiofilm activity. MCFG had better in vitro activity
      than L-AMB against Candida glabrata biofilms, whereas L-AMB had better activity
      than MCFG against Candida albicans and Candida tropicalis biofilms. L-AMB and
      MCFG had comparable efficacy against Candida parapsilosis biofilms. In an in
      vitro lock therapy model, 2 mg/ml L-AMB, unlike 2 mg/ml MCFG, significantly
      reduced the metabolic activity of all the strains of biofilms by >96%. Systemic
      and intraluminal lock treatment with L-AMB for 3-days resulted in more than about
      2 log10 reduction of Candida compared with that of systemic treatment and the
      control group in the C. albicans SP-20012, C. glabrata SP-20040, C. glabrata SP
      20131, C. parapsilosis SP-20137, and C. tropicalis SP-20047 infection models. L
      AMB was more effective at eradicating Candida biofilms in 3-day course of
      systemic and lock therapy than MCFG. L-AMB may be useful for the treatment of
      catheter-related Candida biofilm infections, but this finding will need to be
      confirmed by further studies including a long treatment duration.

PMID- 30209025
TI  - Added Value of Dedicated Spine CT to Detect Fracture in Patients with CT Chest,
      Abdomen, and Pelvis in the Trauma Setting.
AB  - PURPOSE: Fractures of the thoracolumbar spine account for up to 90% of spinal
      fractures, and are associated with significant disability. The advantage of
      acquiring dedicated spine CT imaging in addition to visceral CT studies of the
      chest, abdomen and pelvis for detection of spinal fractures has not been
      definitively established. This retrospective study seeks to determine the
      contribution of dedicated spine CT in the acute clinical setting. METHODS:
      Patients who were diagnosed with fractures of the thoracic or lumbar spine at our
      institution between January 1, 2010 and June 30, 2014 were identified. Additional
      inclusion criteria included having a CT of the chest and/or abdomen and pelvis
      followed by a dedicated thoracic or lumbar spine CT within 30 days. Reports were
      reviewed for accuracy of fracture detection, and missed fractures were
      retrospectively analyzed on images for detectability. RESULTS: A total of 102
      patients met our inclusion criteria for a total of 312 fractures. Of the 312
      fractures, 31 (10%) were missed on the initial visceral CT in 18 of the 102
      patients. In all but two cases, at least one fracture was identified on the
      visceral spine CT. There were no cases in which the newly identified fractures
      changed patient management. CONCLUSION: All fractures requiring surgical
      intervention were identified on the visceral CT. A dedicated spine CT does detect
      additional spine fractures but does not clearly alter patient management.

PMID- 30209028
TI  - Overcoming barriers to vaginal hysterectomy: an analysis of perioperative
      outcomes.
AB  - OBJECTIVES: To determine perioperative outcome differences in patients undergoing
      vaginal hysterectomy based on uterine weight, vaginal delivery and menopausal
      state. METHODS: Retrospective chart review of 452 patients who underwent vaginal
      hysterectomy performed by a single surgeon. Patients' age, vaginal delivery,
      uterine weight, previous pelvic surgery, previous cesarean delivery, removal of
      ovaries were compared, as well as estimated blood loss (EBL), operating room time
      (ORT), length of stay (LOS), intraoperative complications and postoperative
      complications. Multivariable logistic regression was used, and all data were
      analyzed at the level of p<.05 statistical significance using SAS system software
      (SAS Institute Inc., Cary, NC), version 9.3. RESULTS: The mean age was 57.13 +/-
      11.52 years and median vaginal delivery was 2. The uterine weight range was
      16.6gm to 1174.5gm (mean 169.79 +/- 183.94gm). The incidences of blood
      transfusion and bladder injury were 3.03% and 0.66% respectively. Factors shown
      to be associated with longer ORT included greater uterine weight, removal of
      ovaries, posterior repair, TVT sling, prolapse and EBL > 500mL (p<.0001). The
      factors associated with EBL >500mL were greater uterine weight (p=.001), uterine
      myomas (p=.016) and premenopausal state (p=.014). The factors associated with
      conversion to laparotomy were greater uterine weight (p=<0.0001) and
      premenopausal state (p=<0.0017). CONCLUSIONS: Vaginal hysterectomy is a safe and
      feasible approach for patients desiring hysterectomy regardless of uterine weight
      and vaginal delivery.

PMID- 30209026
TI  - Artificial nutrition in patients with cancer has no impact on tumour glucose
      metabolism: Results of the PETANC Study.
AB  - BACKGROUND & AIMS: Nutrition support is recommended in cachexic patients with
      cancer. However, there is no clear evidence about its impact on tumour growth.
      Glycolysis, which is usually higher in cancer than normal cells, can be monitored
      by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F
      FDG PET/CT) imaging that is widely used for cancer staging and therapy efficacy
      assessment. Here, we used 18F-FDG PET/CT imaging to investigate whether
      artificial nutrition has an impact on tumour glucose metabolism in patients with
      cancer and cachexia. METHODS: This prospective study included ten patients with
      histologically proven head and neck or oesophageal cancer. All patients underwent
      18F-FDG PET/CT imaging at baseline and after (parenteral and/or enteral)
      nutrition support on average for 7 days. Tumour glucose metabolism changes were
      evaluated using static (SUVmax, SUVmean and SULpeak) and dynamic (glucose
      metabolic rate and transport constant rates, k) parameters computed from the 18F
      FDG PET/CT data. RESULTS: Artificial nutrition (median energy intake of 21.83
      kcal/kg/day [13.16-45.90], protein intake of 0.84 g/kg/day [0.56-1.64]) was
      administered. Eight patients (80%) received enteral nutrition and two patients
      (20%) parenteral support. Comparison of 18F-FDG PET/CT parameters did not
      highlight any significant difference in tumour glucose metabolism before and
      after the period of nutrition support. CONCLUSIONS: In cachexic patients with
      head and neck or oesophageal cancer, nutrition support administered according to
      the current guidelines shows no impact on tumour glucose metabolism, assessed by
      18F-FDG PET/CT.

PMID- 30209029
TI  - Audio-/Videorecording Clinic Visits for Patient's Personal Use in the United
      States: Cross-Sectional Survey.
AB  - BACKGROUND: Few clinics in the United States routinely offer patients audio or
      video recordings of their clinic visits. While interest in this practice has
      increased, to date, there are no data on the prevalence of recording clinic
      visits in the United States. OBJECTIVE: Our objectives were to (1) determine the
      prevalence of audiorecording clinic visits for patients' personal use in the
      United States, (2) assess the attitudes of clinicians and public toward
      recording, and (3) identify whether policies exist to guide recording practices
      in 49 of the largest health systems in the United States. METHODS: We
      administered 2 parallel cross-sectional surveys in July 2017 to the internet
      panels of US-based clinicians (SERMO Panel) and the US public (Qualtrics Panel).
      To ensure a diverse range of perspectives, we set quotas to capture clinicians
      from 8 specialties. Quotas were also applied to the public survey based on US
      census data (gender, race, ethnicity, and language other than English spoken at
      home) to approximate the US adult population. We contacted 49 of the largest
      health systems (by clinician number) in the United States by email and telephone
      to determine the existence, or absence, of policies to guide audiorecordings of
      clinic visits for patients' personal use. Multiple logistic regression models
      were used to determine factors associated with recording. RESULTS: In total, 456
      clinicians and 524 public respondents completed the surveys. More than one
      quarter of clinicians (129/456, 28.3%) reported that they had recorded a clinic
      visit for patients' personal use, while 18.7% (98/524) of the public reported
      doing so, including 2.7% (14/524) who recorded visits without the clinician's
      permission. Amongst clinicians who had not recorded a clinic visit, 49.5%
      (162/327) would be willing to do so in the future, while 66.0% (346/524) of the
      public would be willing to record in the future. Clinician specialty was
      associated with prior recording: specifically oncology (odds ratio [OR] 5.1, 95%
      CI 1.9-14.9; P=.002) and physical rehabilitation (OR 3.9, 95% CI 1.4-11.6;
      P=.01). Public respondents who were male (OR 2.11, 95% CI 1.26-3.61; P=.005),
      younger (OR 0.73 for a 10-year increase in age, 95% CI 0.60-0.89; P=.002), or
      spoke a language other than English at home (OR 1.99; 95% CI 1.09-3.59; P=.02)
      were more likely to have recorded a clinic visit. None of the large health
      systems we contacted reported a dedicated policy; however, 2 of the 49 health
      systems did report an existing policy that would cover the recording of clinic
      visits for patient use. The perceived benefits of recording included improved
      patient understanding and recall. Privacy and medicolegal concerns were raised.
      CONCLUSIONS: Policy guidance from health systems and further examination of the
      impact of recordings-positive or negative-on care delivery, clinician-related
      outcomes, and patients' behavioral and health-related outcomes is urgently
      required.

PMID- 30209031
TI  - Increased autophagy is cytoprotective against podocyte injury induced by antibody
      and interferon-alpha in lupus nephritis.
AB  - OBJECTIVE: More recent studies suggested that defects in autophagy contribute to
      the pathogenesis of SLE, especially in adaptive immunity. Occurrence and
      progression of lupus nephritis (LN) is the end result of complex interactions
      between regulation of immune responses and pathological process by renal resident
      cells, but there is still a lot of missing information for an establishment on
      the role of autophagy in pathogenesis of LN and as a therapy target. METHODS:
      Systemic and organ-specific aetiologies of autophagy were first evaluated by
      autophagy protein quantification in tissue homogenates in MRL lpr/lpr lupus prone
      and female C57BL mice. Analysis of gene expression was also adopted in human
      blood and urine sediments. Then, some key mediators of the disease, including
      complement inactivated serum, IgG from patients with LN (IgG-LN) and interferon
      (IFN)-alpha were chosen to induce podocyte autophagy. Podocyte injuries including
      apoptosis, podocin derangement, albumin filtration and wound healing were
      monitored simultaneously with autophagy steady-state and flux. RESULTS: Elevated
      LC3B in kidney homogenates and increased autophagosomes in podocyte from MRL
      lpr/lpr were observed. In humans, mRNA levels of some key autophagy genes were
      increased in blood and urinary sediments, and podocyte autophagosomes were
      observed in renal biopsies from patients with LN. Complement inactivated serum,
      IgG-LN and IFN-alpha could induce podocyte autophagy in a time-dependent and
      dosage-dependent manner, and by reactive oxygen species production and mTORC1
      inhibition, respectively. Autophagy inhibition aggravated podocyte damage whereas
      its inducer relieved the injury. CONCLUSION: Podocyte autophagy is activated in
      lupus-prone mice and patients with lupus nephritis. Increased autophagy is
      cytoprotective against antibody and interferon-alpha induced podocyte injury.

PMID- 30209032
TI  - Influence of Molecular Testing on Influenza Diagnosis.

PMID- 30209030
TI  - An e-Prehabilitation System of Care for Teenagers and Young Adults Diagnosed With
      Cancer: Protocol for a Qualitative Co-Design Study.
AB  - BACKGROUND: A diagnosis of cancer in young adulthood can pose many different and
      unique challenges for individuals. The provision of adequate and appropriate
      information as well as care and support for teenagers and young adults at the
      time of diagnosis is central to their health care experience going forward.
      Moreover, appropriate and accessible information provision is critical to ensure
      that young individuals with cancer feel equipped and empowered to make decisions
      about, and be involved in, their treatment and recovery throughout their
      experience; this is a concept known as prehabilitation. As digital interventions
      and resources that support teenagers and young adults with cancer are an
      increasingly desirable part of health care provision, this study will focus on
      the development of an age- and population-appropriate electronic prehabilitation
      (e-Prehabilitation) system of care. OBJECTIVE: We will conduct an exploratory, co
      design research project that will inform the development of an e-Prehabilitation
      system of care to support teenagers and young adults diagnosed with cancer. A
      collaborative approach to data collection and prototype design will ensure that a
      patient-centered approach is embedded throughout. METHODS: A qualitative, co
      design study utilizing surveys, interviews, and focus group discussions is being
      conducted with teenagers and young adults, health care professionals, and
      technologists. RESULTS: This research study is in progress; recruitment and data
      collection activities have commenced and findings are expected in early 2019.
      CONCLUSIONS: The findings of this study will have important implications for
      informing the future development and evaluation of an e-Prehabilitation system of
      care to support teenagers and young adults diagnosed with cancer. REGISTERED
      REPORT IDENTIFIER: RR1-10.2196/10287.

PMID- 30209033
TI  - Correction: Prevalence, incidence and progression of hand osteoarthritis in the
      general population: the Framingham Osteoarthritis Study.

PMID- 30209036
TI  - Local cyclical compression modulates macrophage function in situ and alleviates
      immobilization-induced muscle atrophy.
AB  - Physical inactivity gives rise to numerous diseases and organismal dysfunctions,
      particularly those related to aging. Musculoskeletal disorders including muscle
      atrophy, which can result from a sedentary lifestyle, aggravate locomotive
      malfunction and evoke a vicious circle leading to severe functional disruptions
      of vital organs such as the brain and cardiovascular system. Although the
      significance of physical activity is evident, molecular mechanisms behind its
      beneficial effects are poorly understood. Here, we show that massage-like
      mechanical interventions modulate immobilization-induced pro-inflammatory
      responses of macrophages in situ and alleviate muscle atrophy. Local cyclical
      compression (LCC) on mouse calves, which generates intramuscular pressure waves
      with amplitude of 50 mmHg, partially restores the myofiber thickness and
      contracting forces of calf muscles that are decreased by hindlimb immobilization.
      LCC tempers the increase in the number of cells expressing pro-inflammatory
      proteins, tumor necrosis factor-alpha and monocyte chemoattractant protein-1 (MCP
      1), including macrophages in situ The reversing effect of LCC on immobilization
      induced thinning of myofibers is almost completely nullified when macrophages
      recruited from circulating blood are depleted by administration of clodronate
      liposomes. Furthermore, application of pulsatile fluid shear stress, but not
      hydrostatic pressure, reduces the expression of MCP-1 in macrophages in vitro
      Together with the LCC-induced movement of intramuscular interstitial fluid
      detected by uCT analysis, these results suggest that mechanical modulation of
      macrophage function is involved in physical inactivity-induced muscle atrophy and
      inflammation. Our findings uncover the implication of mechanosensory function of
      macrophages in disuse muscle atrophy, thereby opening a new path to develop a
      novel therapeutic strategy utilizing mechanical interventions.

PMID- 30209037
TI  - Metabolism of c-Met Kinase Inhibitors Containing Quinoline by Aldehyde Oxidase,
      Electron Donating, and Steric Hindrance Effect.
AB  - Some quinoline-containing c-Met kinase inhibitors are aldehyde oxidase (AO)
      substrates. 3-Substituted quinoline triazolopyridine analogs were synthesized to
      understand the electron-donating and steric hindrance effects on AO-mediated
      metabolism. Metabolic stability studies for these quinoline analogs were carried
      out in liver cytosol from mice, rats, cynomolgus monkeys, and humans. Several 3-N
      substituted analogs were found to be unstable in monkey liver cytosolic
      incubations (half-life, <10 minutes), and five of them (63, 53, 51, 11, and 71)
      were chosen for additional mechanistic studies. Mono-oxygenation on the quinoline
      ring was identified by liquid chromatography tandem mass spectrometry. Metabolite
      formation was inhibited by the AO inhibitors menadione and raloxifene, but not by
      the xanthine oxidase inhibitor allopurinol. It was found that small electron
      donating groups at the 3-quinoline moiety made the analogs more susceptible to AO
      metabolism, whereas large 3-substituents could reverse the trend. Although
      species differences were observed, this trend was applicable to all species
      tested. Small electron-donating substituents at the 3-quinoline moiety increased
      both affinity (decreased Michaelis constant) and V max maximum velocity toward AO
      in kinetic studies, whereas large substituents decreased both parameters probably
      as a result of steric hindrance. Based on our analysis, a common structural
      feature with high AO liability was proposed. Our finding could provide useful
      information for chemists to minimize potential AO liability when designing
      quinoline analogs.

PMID- 30209040
TI  - Energetic increases lead to niche packing in deep-sea wood falls.
AB  - Mechanisms leading to variation in diversity over energetic gradients continue to
      challenge ecologists. Changes in diversity may reflect the environmental capacity
      to support species' coexistence through increased niche packing or niche space
      expansion. Current ecological theory predicts that increases in energy may lead
      to both scenarios but not their relative strengths. We use experimental deep-sea,
      wood-fall communities, where energy supply can be controlled, to test for the
      importance of niche expansion and packing in functional space over an energetic
      gradient. Invertebrate communities were identified and counted from 16 Acacia sp.
      logs ranging in size from 0.6 to 20.6 kg in mass (corresponding to energy
      availability) deployed at 3203 m in the Pacific Ocean for 5 years. We use four
      fundamental energetic species-level functional traits-food source, trophic
      category, motility and tiering-to characterize species niches. Increases in
      energy on wood falls lead to increases in species richness. This higher species
      richness resulted from a substantial increase in mean niche overlap, suggesting
      that increases in energy may afford reduced competition.

PMID- 30209038
TI  - Periodontal cell mechanotransduction.
AB  - The periodontium is a structurally and functionally complex tissue that
      facilitates the anchorage of teeth in jaws. The periodontium consists of various
      cell types including stem cells, fibroblasts and epithelial cells. Cells of the
      periodontium are constantly exposed to mechanical stresses generated by
      biological processes such as the chewing motions of teeth, by flows generated by
      tongue motions and by forces generated by implants. Mechanical stresses modulate
      the function of cells in the periodontium, and may play a significant role in the
      development of periodontal disease. Here, we review the literature on the effect
      of mechanical forces on periodontal cells in health and disease with an emphasis
      on molecular and cellular mechanisms.

PMID- 30209041
TI  - The dynamic role of the ilio-sacral joint in jumping frogs.
AB  - A striking feature among jumping frogs is a sharp pelvic bend about the ilio
      sacral (IS) joint, unique to anurans. Although this sagittal plane hinge has been
      interpreted as crucial for the evolution of jumping, its mechanical contribution
      has not been quantified. Using a model based on Kassina maculata and animated
      with kinematics from prior experiments, we solved the ground contact dynamics in
      MuJoCo enabling inverse dynamics without force plate measurements. We altered the
      magnitude, speed and direction of IS extension (leaving remaining kinematics
      unaltered) to determine its role in jumping. Ground reaction forces (GRFs)
      matched recorded data. Prior work postulated that IS rotation facilitates jumping
      by aligning the torso with the GRF. However, our simulations revealed that static
      torso orientation has little effect on GRF due to the close proximity of the IS
      joint with the COM, failing to support the 'torso alignment' hypothesis. Rather
      than a postural role, IS rotation has a dynamic function whereby angular
      acceleration (i) influences GRF direction to modulate jump direction and (ii)
      increases joint loading, particularly at the ankle and knee, perhaps increasing
      tendon elastic energy storage early in jumps. Findings suggest that the pelvic
      hinge mechanism is not obligatory for jumping, but rather crucial for the fine
      tuning of jump trajectory, particularly in complex habitats.

PMID- 30209035
TI  - Treatment of Toxoplasmosis: Historical Perspective, Animal Models, and Current
      Clinical Practice.
AB  - SUMMARYPrimary Toxoplasma gondii infection is usually subclinical, but cervical
      lymphadenopathy or ocular disease can be present in some patients. Active
      infection is characterized by tachyzoites, while tissue cysts characterize latent
      disease. Infection in the fetus and in immunocompromised patients can cause
      devastating disease. The combination of pyrimethamine and sulfadiazine (pyr
      sulf), targeting the active stage of the infection, is the current gold standard
      for treating toxoplasmosis, but failure rates remain significant. Although other
      regimens are available, including pyrimethamine in combination with clindamycin,
      atovaquone, clarithromycin, or azithromycin or monotherapy with trimethoprim
      sulfamethoxazole (TMP-SMX) or atovaquone, none have been found to be superior to
      pyr-sulf, and no regimen is active against the latent stage of the infection.
      Furthermore, the efficacy of these regimens against ocular disease remains
      uncertain. In multiple studies, systematic screening for Toxoplasma infection
      during gestation, followed by treatment with spiramycin for acute maternal
      infections and with pyr-sulf for those with established fetal infection, has been
      shown to be effective at preventing vertical transmission and minimizing the
      severity of congenital toxoplasmosis (CT). Despite significant progress in
      treating human disease, there is a strong impetus to develop novel therapeutics
      for both the acute and latent forms of the infection. Here we present an overview
      of toxoplasmosis treatment in humans and in animal models. Additional research is
      needed to identify novel drugs by use of innovative high-throughput screening
      technologies and to improve experimental models to reflect human disease. Such
      advances will pave the way for lead candidates to be tested in thoroughly
      designed clinical trials in defined patient populations.

PMID- 30209042
TI  - Latent power of basking sharks revealed by exceptional breaching events.
AB  - The fast swimming and associated breaching behaviour of endothermic mackerel
      sharks is well suited to the capture of agile prey. In contrast, the observed but
      rarely documented breaching capability of basking sharks is incongruous to their
      famously languid lifestyle as filter-feeding planktivores. Indeed, by analysing
      video footage and an animal-instrumented data logger, we found that basking
      sharks exhibit the same vertical velocity (approx. 5 m s-1) during breach events
      as the famously powerful predatory great white shark. We estimate that an 8-m,
      2700-kg basking shark, recorded breaching at 5 m s-1 and accelerating at 0.4 m s
      2, expended mechanical energy at a rate of 5.5 W kg-1; a mass-specific energetic
      cost comparable to that of the great white shark. The energy cost of such a
      breach is equivalent to around 1/17th of the daily standard metabolic cost for a
      basking shark, while the ratio is about half this for a great white shark. While
      breaches by basking sharks must serve a different function to white shark
      breaches, their similar breaching speeds questions our perception of the
      physiology of large filter-feeding fish.

PMID- 30209039
TI  - Tales from the crypt: intestinal niche signals in tissue renewal, plasticity and
      cancer.
AB  - Rapidly renewing tissues such as the intestinal epithelium critically depend on
      the activity of small-sized stem cell populations that continuously generate new
      progeny to replace lost and damaged cells. The complex and tightly regulated
      process of intestinal homeostasis is governed by a variety of signalling pathways
      that balance cell proliferation and differentiation. Accumulating evidence
      suggests that stem cell control and daughter cell fate determination is largely
      dictated by the microenvironment. Here, we review recent developments in the
      understanding of intestinal stem cell dynamics, focusing on the roles, mechanisms
      and interconnectivity of prime signalling pathways that regulate stem cell
      behaviour in intestinal homeostasis. Furthermore, we discuss how mutational
      activation of these signalling pathways endows colorectal cancer cells with niche
      independent growth advantages during carcinogenesis.

PMID- 30209043
TI  - Integrated human-virus metabolic stoichiometric modelling predicts host-based
      antiviral targets against Chikungunya, Dengue and Zika viruses.
AB  - Current and reoccurring viral epidemic outbreaks such as those caused by the Zika
      virus illustrate the need for rapid development of antivirals. Such development
      would be facilitated by computational approaches that can provide experimentally
      testable predictions for possible antiviral strategies. To this end, we focus
      here on the fact that viruses are directly dependent on their host metabolism for
      reproduction. We develop a stoichiometric, genome-scale metabolic model that
      integrates human macrophage cell metabolism with the biochemical demands arising
      from virus production and use it to determine the virus impact on host metabolism
      and vice versa. While this approach applies to any host-virus pair, we first
      apply it to currently epidemic viruses Chikungunya, Dengue and Zika in this
      study. We find that each of these viruses causes specific alterations in the host
      metabolic flux towards fulfilling their biochemical demands as predicted by their
      genome and capsid structure. Subsequent analysis of this integrated model allows
      us to predict a set of host reactions, which, when constrained, inhibit virus
      production. We show that this prediction recovers known targets of existing
      antiviral drugs, specifically those targeting nucleotide production, while
      highlighting a set of hitherto unexplored reactions involving both amino acid and
      nucleotide metabolic pathways, with either broad or virus-specific antiviral
      potential. Thus, this computational approach allows rapid generation of
      experimentally testable hypotheses for novel antiviral targets within a host.

PMID- 30209047
TI  - Managing blood pressure medication at discharge.

PMID- 30209044
TI  - Epidemic dynamics, interactions and predictability of enteroviruses associated
      with hand, foot and mouth disease in Japan.
AB  - Outbreaks of hand, foot and mouth disease have been documented in Japan since
      1963. This disease is primarily caused by the two closely related serotypes of
      Enterovirus A71 (EV-A71) and Coxsackievirus A16 (CV-A16). Here, we analyse
      Japanese virologic and syndromic surveillance time-series data from 1982 to 2015.
      As in some other countries in the Asia Pacific region, EV-A71 in Japan has a 3
      year cyclical component, whereas CV-A16 is predominantly annual. We observe
      empirical signatures of an inhibitory interaction between the serotypes;
      virologic lines of evidence suggest they may indeed interact immunologically. We
      fit the time series to mechanistic epidemiological models: as a first-order
      effect, we find the data consistent with single-serotype susceptible-infected
      recovered dynamics. We then extend the modelling to incorporate an inhibitory
      interaction between serotypes. Our results suggest the existence of a transient
      cross-protection and possible asymmetry in its strength such that CV-A16 serves
      as a stronger forcing on EV-A71. Allowing for asymmetry yields accurate out-of
      sample predictions and the directionality of this effect is consistent with the
      virologic literature. Confirmation of these hypothesized interactions would have
      important implications for understanding enterovirus epidemiology and informing
      vaccine development. Our results highlight the general implication that even
      subtle interactions could have qualitative impacts on epidemic dynamics and
      predictability.

PMID- 30209048
TI  - Going paper free: five minutes with Martin Kelsall.

PMID- 30209046
TI  - Strategic decision making about travel during disease outbreaks: a game
      theoretical approach.
AB  - Visitors can play an important role in the spread of infections. Here, we
      incorporate an epidemic model into a game theoretical framework to investigate
      the effects of travel strategies on infection control. Potential visitors must
      decide whether to travel to a destination that is at risk of infectious disease
      outbreaks. We compare the individually optimal (Nash equilibrium) strategy to the
      group optimal strategy that maximizes the overall population utility. Economic
      epidemiological models often find that individual and group optimal strategies
      are very different. By contrast, we find perfect agreement between individual and
      group optimal strategies across a wide parameter regime. For more limited regimes
      where disagreement does occur, the disagreement is (i) generally very extreme;
      (ii) highly sensitive to small changes in infection transmissibility and visitor
      costs/benefits; and (iii) can manifest either in a higher travel volume for
      individual optimal than group optimal strategies, or vice versa. The simulations
      show qualitative agreement with the 2003 severe acute respiratory syndrome (SARS)
      outbreak in Beijing, China. We conclude that a conflict between individual and
      group optimal visitor travel strategies during outbreaks may not generally be a
      problem, although extreme differences could emerge suddenly under certain changes
      in economic and epidemiological conditions.

PMID- 30209049
TI  - Global hunger grows amid conflict and climate change.

PMID- 30209045
TI  - Multiplex core-periphery organization of the human connectome.
AB  - What is the core of the human brain is a fundamental question that has been
      mainly addressed by studying the anatomical connections between differently
      specialized areas, thus neglecting the possible contributions from their
      functional interactions. While many methods are available to identify the core of
      a network when connections between nodes are all of the same type, a principled
      approach to define the core when multiple types of connectivity are allowed is
      still lacking. Here, we introduce a general framework to define and extract the
      core-periphery structure of multi-layer networks by explicitly taking into
      account the connectivity patterns at each layer. We first validate our algorithm
      on synthetic networks of different size and density, and with tunable overlap
      between the cores at different layers. We then use our method to merge
      information from structural and functional brain networks, obtaining in this way
      an integrated description of the core of the human connectome. Results confirm
      the role of the main known cortical and subcortical hubs, but also suggest the
      presence of new areas in the sensori-motor cortex that are crucial for intrinsic
      brain functioning. Taken together these findings provide fresh evidence on a
      fundamental question in modern neuroscience and offer new opportunities to
      explore the mesoscale properties of multimodal brain networks.

PMID- 30209051
TI  - Regulatory response to contaminated valsartan.

PMID- 30209053
TI  - Dubhfeasa Slattery: Professional professionalist.

PMID- 30209050
TI  - Effect of high dose folic acid supplementation in pregnancy on pre-eclampsia
      (FACT): double blind, phase III, randomised controlled, international,
      multicentre trial.
AB  - OBJECTIVE: To determine the efficacy of high dose folic acid supplementation for
      prevention of pre-eclampsia in women with at least one risk factor: pre-existing
      hypertension, prepregnancy diabetes (type 1 or 2), twin pregnancy, pre-eclampsia
      in a previous pregnancy, or body mass index >=35. DESIGN: Randomised, phase III,
      double blinded international, multicentre clinical trial. SETTING: 70 obstetrical
      centres in five countries (Argentina, Australia, Canada, Jamaica, and UK).
      PARTICIPANTS: 2464 pregnant women with at least one high risk factor for pre
      eclampsia were randomised between 2011 and 2015 (1144 to the folic acid group and
      1157 to the placebo group); 2301 were included in the intention to treat
      analyses. INTERVENTION: Eligible women were randomised to receive either daily
      high dose folic acid (four 1.0 mg oral tablets) or placebo from eight weeks of
      gestation to the end of week 16 of gestation until delivery. Clinicians,
      participants, adjudicators, and study staff were masked to study treatment
      allocation. MAIN OUTCOME MEASURE: The primary outcome was pre-eclampsia, defined
      as hypertension presenting after 20 weeks' gestation with major proteinuria or
      HELLP syndrome (haemolysis, elevated liver enzymes, low platelets). RESULTS: Pre
      eclampsia occurred in 169/1144 (14.8%) women in the folic acid group and 156/1157
      (13.5%) in the placebo group (relative risk 1.10, 95% confidence interval 0.90 to
      1.34; P=0.37). There was no evidence of differences between the groups for any
      other adverse maternal or neonatal outcomes. CONCLUSION: Supplementation with 4.0
      mg/day folic acid beyond the first trimester does not prevent pre-eclampsia in
      women at high risk for this condition. TRIAL REGISTRATION: Current Controlled
      Trials ISRCTN23781770 and ClinicalTrials.gov NCT01355159.

PMID- 30209052
TI  - Intensification of older adults' outpatient blood pressure treatment at hospital
      discharge: national retrospective cohort study.
AB  - OBJECTIVES: To assess how often older adults admitted to hospital for common non
      cardiac conditions were discharged with intensified antihypertensive treatment,
      and to identify markers of appropriateness for these intensifications. DESIGN:
      Retrospective cohort study. SETTING: US Veterans Administration Health System.
      PARTICIPANTS: Patients aged 65 years or over with hypertension admitted to
      hospital with non-cardiac conditions between 2011 and 2013. MAIN OUTCOME
      MEASURES: Intensification of antihypertensive treatment, defined as receiving a
      new or higher dose antihypertensive agent at discharge compared with drugs used
      before admission. Hierarchical logistic regression analyses were used to control
      for characteristics of patients and hospitals. RESULTS: Among 14 915 older adults
      (median age 76, interquartile range 69-84), 9636 (65%) had well controlled
      outpatient blood pressure before hospital admission. Overall, 2074 (14%) patients
      were discharged with intensified antihypertensive treatment, more than half of
      whom (1082) had well controlled blood pressure before admission. After adjustment
      for potential confounders, elevated inpatient blood pressure was strongly
      associated with being discharged on intensified antihypertensive regimens. Among
      patients with previously well controlled outpatient blood pressure, 8% (95%
      confidence interval 7% to 9%) of patients without elevated inpatient blood
      pressure, 24% (21% to 26%) of patients with moderately elevated inpatient blood
      pressure, and 40% (34% to 46%) of patients with severely elevated inpatient blood
      pressure were discharged with intensified antihypertensive regimens. No
      differences were seen in rates of intensification among patients least likely to
      benefit from tight blood pressure control (limited life expectancy, dementia, or
      metastatic malignancy), nor in those most likely to benefit (history of
      myocardial infarction, cerebrovascular disease, or renal disease). CONCLUSIONS:
      One in seven older adults admitted to hospital for common non-cardiac conditions
      were discharged with intensified antihypertensive treatment. More than half of
      intensifications occurred in patients with previously well controlled outpatient
      blood pressure. More attention is needed to reduce potentially harmful
      overtreatment of blood pressure as older adults transition from hospital to home.

PMID- 30209054
TI  - Sixty seconds on . . . neonatal herpes.

PMID- 30209055
TI  - Is cancer fundraising fuelling quackery?

PMID- 30209056
TI  - Doctors' personal reflections should not include case details, says new guidance.

PMID- 30209057
TI  - Use of N-nitrosodimethylamine (NDMA) contaminated valsartan products and risk of
      cancer: Danish nationwide cohort study.
AB  - OBJECTIVE: To perform an expedited assessment of cancer risk associated with
      exposure to N-nitrosodimethylamine (NDMA) through contaminated valsartan
      products. DESIGN: Nationwide cohort study. SETTING: Danish health registries on
      individual level prescription drug use, cancer occurrence, and hospital
      diagnoses. PARTICIPANTS: 5150 Danish patients with no history of cancer, aged 40
      years or older, and using valsartan at 1 January 2012 or initiating use between 1
      January 2012 and 30 June 2017. Participants were followed from one year after
      cohort entry (lag time period) until experiencing a cancer outcome, death,
      migration, or end of study period (30 June 2018). Each participant's exposure to
      NDMA (ever exposure and predefined categories of cumulative valsartan exposure)
      was mapped out as a time varying variable while also applying a one year lag.
      MAIN OUTCOME MEASURES: Association between NDMA exposure and a primary composite
      endpoint comprising all cancers except non-melanoma skin cancer, estimated using
      Cox regression. In supplementary analyses, the risk of individual cancers was
      determined. RESULTS: The final cohort comprised 5150 people followed for a median
      of 4.6 years. In total, 3625 cohort participants contributed 7344 person years
      classified as unexposed to NDMA, and 3450 participants contributed 11 920 person
      years classified as ever exposed to NDMA. With 104 cancer outcomes among NDMA
      unexposed participants and 198 among exposed participants, the adjusted hazard
      ratio for overall cancer was 1.09 (95% confidence interval 0.85 to 1.41), with no
      evidence of a dose-response relation (P=0.70). For single cancer outcomes,
      increases in risk were observed for colorectal cancer (hazard ratio 1.46, 95%
      confidence interval 0.79 to 2.73) and for uterine cancer (1.81, 0.55 to 5.90),
      although with wide confidence intervals that included the null. CONCLUSIONS: The
      results do not imply a markedly increased short term overall risk of cancer in
      users of valsartan contaminated with NDMA. However, uncertainty persists about
      single cancer outcomes, and studies with longer follow-up are needed to assess
      long term cancer risk.

PMID- 30209059
TI  - Half of all European clinical trials break rules on reporting results within a
      year.

PMID- 30209060
TI  - Tackling burnout in UK trainee doctors is vital for a sustainable, safe, high
      quality NHS.

PMID- 30209058
TI  - Compliance with requirement to report results on the EU Clinical Trials Register:
      cohort study and web resource.
AB  - OBJECTIVES: To ascertain compliance rates with the European Commission's
      requirement that all trials on the EU Clinical Trials Register (EUCTR) post
      results to the registry within 12 months of completion (final compliance date 21
      December 2016); to identify features associated with non-compliance; to rank
      sponsors by compliance; and to build a tool for live ongoing audit of compliance.
      DESIGN: Retrospective cohort study. SETTING: EUCTR. PARTICIPANTS: 7274 of 11 531
      trials listed as completed on EUCTR and where results could be established as
      due. MAIN OUTCOME MEASURE: Publication of results on EUCTR. RESULTS: Of 7274
      trials where results were due, 49.5% (95% confidence interval 48.4% to 50.7%)
      reported results. Trials with a commercial sponsor were substantially more likely
      to post results than those with a non-commercial sponsor (68.1% v 11.0%, adjusted
      odds ratio 23.2, 95% confidence interval 19.2 to 28.2); as were trials by a
      sponsor who conducted a large number of trials (77.9% v 18.4%, adjusted odds
      ratio 18.4, 15.3 to 22.1). More recent trials were more likely to report results
      (per year odds ratio 1.05, 95% confidence interval 1.03 to 1.07). Extensive
      evidence was found of errors, omissions, and contradictory entries in EUCTR data
      that prevented ascertainment of compliance for some trials. CONCLUSIONS:
      Compliance with the European Commission requirement for all trials to post
      results on to the EUCTR within 12 months of completion has been poor, with half
      of all trials non-compliant. EU registry data commonly contain inconsistencies
      that might prevent even regulators assessing compliance. Accessible and timely
      information on the compliance status of each individual trial and sponsor may
      help to improve reporting rates.

PMID- 30209061
TI  - Antibody-Neutralized Reovirus Is Effective in Oncolytic Virotherapy.
AB  - Immunotherapy is showing promise for otherwise incurable cancers. Oncolytic
      viruses (OVs), developed as direct cytotoxic agents, mediate their antitumor
      effects via activation of the immune system. However, OVs also stimulate
      antiviral immune responses, including the induction of OV-neutralizing
      antibodies. Current dogma suggests that the presence of preexisting antiviral
      neutralizing antibodies in patients, or their development during viral therapy,
      is a barrier to systemic OV delivery, rendering repeat systemic treatments
      ineffective. However, we have found that human monocytes loaded with preformed
      reovirus-antibody complexes, in which the reovirus is fully neutralized, deliver
      functional replicative reovirus to tumor cells, resulting in tumor cell infection
      and lysis. This delivery mechanism is mediated, at least in part, by antibody
      receptors (in particular FcgammaRIII) that mediate uptake and internalization of
      the reovirus/antibody complexes by the monocytes. This finding has implications
      for oncolytic virotherapy and for the design of clinical OV treatment strategies.
      Cancer Immunol Res; 6(10); 1161-73. (c)2018 AACR.

PMID- 30209063
TI  - Leading hospital suspends complex heart surgery to maintain patient safety.

PMID- 30209064
TI  - Yet another risk score-will it really help decision making?

PMID- 30209062
TI  - Stromal Fibroblasts Mediate Anti-PD-1 Resistance via MMP-9 and Dictate TGFbeta
      Inhibitor Sequencing in Melanoma.
AB  - Although anti-PD-1 therapy has improved clinical outcomes for select patients
      with advanced cancer, many patients exhibit either primary or adaptive resistance
      to checkpoint inhibitor immunotherapy. The role of the tumor stroma in the
      development of these mechanisms of resistance to checkpoint inhibitors remains
      unclear. We demonstrated that pharmacologic inhibition of the TGFbeta signaling
      pathway synergistically enhanced the efficacy of anti-CTLA-4 immunotherapy but
      failed to augment anti-PD-1/PD-L1 responses in an autochthonous model of
      BRAFV600E melanoma. Additional mechanistic studies revealed that TGFbeta pathway
      inhibition promoted the proliferative expansion of stromal fibroblasts, thereby
      facilitating MMP-9-dependent cleavage of PD-L1 surface expression, leading to
      anti-PD-1 resistance in this model. Further work demonstrated that melanomas
      escaping anti-PD-1 therapy exhibited a mesenchymal phenotype associated with
      enhanced TGFbeta signaling activity. Delayed TGFbeta inhibitor therapy, following
      anti-PD-1 escape, better served to control further disease progression and was
      superior to a continuous combination of anti-PD-1 and TGFbeta inhibition. This
      work illustrates that formulating immunotherapy combination regimens to enhance
      the efficacy of checkpoint blockade requires an in-depth understanding of the
      impact of these agents on the tumor microenvironment. These data indicated that
      stromal fibroblast MMP-9 may desensitize tumors to anti-PD-1 and suggests that
      TGFbeta inhibition may generate greater immunologic efficacy when administered
      following the development of acquired anti-PD-1 resistance.See related Spotlight
      on p. 1444.

PMID- 30209065
TI  - Why is the search for pre-eclampsia prevention so elusive?

PMID- 30209066
TI  - The TLR7/8/9 Antagonist IMO-8503 Inhibits Cancer-Induced Cachexia.
AB  - : Muscle wasting is a feature of the cachexia syndrome, which contributes
      significantly to the mortality of patients with cancer. We have previously
      demonstrated that miR-21 is secreted through extracellular vesicles (EV) by lung
      and pancreatic cancer cells and promotes JNK-dependent cell death through its
      binding to the TLR7 receptor in murine myoblasts. Here, we evaluate the ability
      of IMO-8503, a TLR7, 8, and 9 antagonist, to inhibit cancer-induced cachexia.
      Using EVs isolated from lung and pancreatic cancer cells and from patient plasma
      samples, we demonstrate that IMO-8503 inhibits cell death induced by circulating
      miRNAs with no significant toxicity. Intraperitoneal administration of the
      antagonist in a murine model for Lewis lung carcinoma (LLC-induced cachexia)
      strongly impaired several cachexia-related features, such as the expression of
      Pax7 as well as caspase-3 and PARP cleavage in skeletal muscles, and
      significantly prevented the loss of lean mass in tumor-bearing mice. IMO-8503
      also impaired circulating miRNA-induced cell death in human primary myoblasts.
      Taken together, our findings strongly indicate that IMO-8503 serves as a
      potential therapy for the treatment of cancer cachexia. SIGNIFICANCE: Cancer
      associated cachexia is a significant problem for patients with cancer that remain
      poorly understood, understudied, and inadequately treated; these findings report
      a potential new therapeutic for the treatment of TLR7-mediated cancer cachexia.

PMID- 30209034
TI  - Methicillin-Resistant Staphylococcus aureus: Molecular Characterization,
      Evolution, and Epidemiology.
AB  - SUMMARYStaphylococcus aureus, a major human pathogen, has a collection of
      virulence factors and the ability to acquire resistance to most antibiotics. This
      ability is further augmented by constant emergence of new clones, making S.
      aureus a "superbug." Clinical use of methicillin has led to the appearance of
      methicillin-resistant S. aureus (MRSA). The past few decades have witnessed the
      existence of new MRSA clones. Unlike traditional MRSA residing in hospitals, the
      new clones can invade community settings and infect people without predisposing
      risk factors. This evolution continues with the buildup of the MRSA reservoir in
      companion and food animals. This review focuses on imparting a better
      understanding of MRSA evolution and its molecular characterization and
      epidemiology. We first describe the origin of MRSA, with emphasis on the diverse
      nature of staphylococcal cassette chromosome mec (SCCmec). mecA and its new
      homologues (mecB, mecC, and mecD), SCCmec types (13 SCCmec types have been
      discovered to date), and their classification criteria are discussed. The review
      then describes various typing methods applied to study the molecular epidemiology
      and evolutionary nature of MRSA. Starting with the historical methods and
      continuing to the advanced whole-genome approaches, typing of collections of MRSA
      has shed light on the origin, spread, and evolutionary pathways of MRSA clones.

PMID- 30209067
TI  - Zebrafish blastomere screen identifies retinoic acid suppression of MYB in
      adenoid cystic carcinoma.
AB  - Pluripotent cells have been used to probe developmental pathways that are
      involved in genetic diseases and oncogenic events. To find new therapies that
      would target MYB-driven tumors, we developed a pluripotent zebrafish blastomere
      culture system. We performed a chemical genetic screen and identified retinoic
      acid agonists as suppressors of c-myb expression. Retinoic acid treatment also
      decreased c-myb gene expression in human leukemia cells. Translocations that
      drive overexpression of the oncogenic transcription factor MYB are molecular
      hallmarks of adenoid cystic carcinoma (ACC), a malignant salivary gland tumor
      with no effective therapy. Retinoic acid agonists inhibited tumor growth in vivo
      in ACC patient-derived xenograft models and decreased MYB binding at translocated
      enhancers, thereby potentially diminishing the MYB positive feedback loop driving
      ACC. Our findings establish the zebrafish pluripotent cell culture system as a
      method to identify modulators of tumor formation, particularly establishing
      retinoic acid as a potential new effective therapy for ACC.

PMID- 30209070
TI  - Cytosolic Recognition of Microbes and Pathogens: Inflammasomes in Action.
AB  - Infection is a dynamic biological process underpinned by a complex interplay
      between the pathogen and the host. Microbes from all domains of life, including
      bacteria, viruses, fungi, and protozoan parasites, have the capacity to cause
      infection. Infection is sensed by the host, which often leads to activation of
      the inflammasome, a cytosolic macromolecular signaling platform that mediates the
      release of the proinflammatory cytokines interleukin-1beta (IL-1beta) and IL-18
      and cleavage of the pore-forming protein gasdermin D, leading to pyroptosis. Host
      mediated sensing of the infection occurs when pathogens inject or carry pathogen
      associated molecular patterns (PAMPs) into the cytoplasm or induce damage that
      causes cytosolic liberation of danger-associated molecular patterns (DAMPs) in
      the host cell. Recognition of PAMPs and DAMPs by inflammasome sensors, including
      NLRP1, NLRP3, NLRC4, NAIP, AIM2, and Pyrin, initiates a cascade of events that
      culminate in inflammation and cell death. However, pathogens can deploy virulence
      factors capable of minimizing or evading host detection. This review presents a
      comprehensive overview of the mechanisms of microbe-induced activation of the
      inflammasome and the functional consequences of inflammasome activation in
      infectious diseases. We also explore the microbial strategies used in the evasion
      of inflammasome sensing at the host-microbe interaction interface.

PMID- 30209068
TI  - Xrp1 genetically interacts with the ALS-associated FUS orthologue caz and
      mediates its toxicity.
AB  - Cabeza (caz) is the single Drosophila melanogaster orthologue of the human FET
      proteins FUS, TAF15, and EWSR1, which have been implicated in amyotrophic lateral
      sclerosis (ALS) and frontotemporal dementia. In this study, we identified Xrp1, a
      nuclear chromatin-binding protein, as a key modifier of caz mutant phenotypes.
      Xrp1 expression was strongly up-regulated in caz mutants, and Xrp1 heterozygosity
      rescued their motor defects and life span. Interestingly, selective neuronal Xrp1
      knockdown was sufficient to rescue, and neuronal Xrp1 overexpression phenocopied
      caz mutant phenotypes. The caz/Xrp1 genetic interaction depended on the
      functionality of the AT-hook DNA-binding domain in Xrp1, and the majority of Xrp1
      interacting proteins are involved in gene expression regulation. Consistently,
      caz mutants displayed gene expression dysregulation, which was mitigated by Xrp1
      heterozygosity. Finally, Xrp1 knockdown substantially rescued the motor deficits
      and life span of flies expressing ALS mutant FUS in motor neurons, implicating
      gene expression dysregulation in ALS-FUS pathogenesis.

PMID- 30209069
TI  - The kinetoplastid kinetochore protein KKT4 is an unconventional microtubule tip
      coupling protein.
AB  - Kinetochores are multiprotein machines that drive chromosome segregation by
      maintaining persistent, load-bearing linkages between chromosomes and dynamic
      microtubule tips. Kinetochores in commonly studied eukaryotes bind microtubules
      through widely conserved components like the Ndc80 complex. However, in
      evolutionarily divergent kinetoplastid species such as Trypanosoma brucei, which
      causes sleeping sickness, the kinetochores assemble from a unique set of proteins
      lacking homology to any known microtubule-binding domains. Here, we show that the
      T. brucei kinetochore protein KKT4 binds directly to microtubules and maintains
      load-bearing attachments to both growing and shortening microtubule tips. The
      protein localizes both to kinetochores and to spindle microtubules in vivo, and
      its depletion causes defects in chromosome segregation. We define a microtubule
      binding domain within KKT4 and identify several charged residues important for
      its microtubule-binding activity. Thus, despite its lack of significant
      similarity to other known microtubule-binding proteins, KKT4 has key functions
      required for driving chromosome segregation. We propose that it represents a
      primary element of the kinetochore-microtubule interface in kinetoplastids.

PMID- 30209071
TI  - Interplay between Peptidoglycan Biology and Virulence in Gram-Negative Pathogens.
AB  - The clinical and epidemiological threat of the growing antimicrobial resistance
      in Gram-negative pathogens, particularly for beta-lactams, the most frequently
      used and relevant antibiotics, urges research to find new therapeutic weapons to
      combat the infections caused by these microorganisms. An essential previous step
      in the development of these therapeutic solutions is to identify their potential
      targets in the biology of the pathogen. This is precisely what we sought to do in
      this review specifically regarding the barely exploited field analyzing the
      interplay among the biology of the peptidoglycan and related processes, such as
      beta-lactamase regulation and virulence. Hence, here we gather, analyze, and
      integrate the knowledge derived from published works that provide information on
      the topic, starting with those dealing with the historically neglected essential
      role of the Gram-negative peptidoglycan in virulence, including structural,
      biogenesis, remodeling, and recycling aspects, in addition to proinflammatory and
      other interactions with the host. We also review the complex link between
      intrinsic beta-lactamase production and peptidoglycan metabolism, as well as the
      biological costs potentially associated with the expression of horizontally
      acquired beta-lactamases. Finally, we analyze the existing evidence from multiple
      perspectives to provide useful clues for identifying targets enabling the future
      development of therapeutic options attacking the peptidoglycan-virulence
      interconnection as a key weak point of the Gram-negative pathogens to be used, if
      not to kill the bacteria, to mitigate their capacity to produce severe
      infections.

PMID- 30209072
TI  - The genomes uncoupled Mutants Are More Sensitive to Norflurazon Than Wild Type.

PMID- 30209074
TI  - Nijmegen Breakage Syndrome Complicated With Primary Pulmonary Granulomas.
AB  - Nijmegen breakage syndrome (NBS) is a rare autosomal recessive disease
      characterized by microcephaly, growth retardation, severe immunodeficiency, and
      predisposition to lymphoid malignancy. In this report, we describe a case of a 9
      year-old boy, previously diagnosed with NBS and symptoms of dyspnea, dry cough,
      and fever. Despite initial recognition of pneumonia, there was no response to
      broad spectrum antimicrobial treatment, negative results from microbiological
      tests, and unclear changes in lung imaging were observed. Therefore, further
      diagnostics were focused on suspected lymphoid malignancy and involved lung
      biopsy. Unexpectedly, histopathological examination revealed noncaseating
      granulomas. The introduction of systemic steroids resulted in significant
      improvement of the patient's clinical condition. This is the first description of
      primary pulmonary noncaseating granulomas without nodular involvement in a child
      with NBS.

PMID- 30209073
TI  - Use of scratchcards for allocation concealment in a prehospital randomised
      controlled trial.
AB  - BACKGROUND: Rapid Analgesia for Prehospital Hip Disruption was a small study
      designed to determine the feasibility of undertaking a randomised controlled
      trial (RCT) to test the clinical and cost-effectiveness of paramedics
      administering Fascia Iliaca Compartment Block as early prehospital pain relief to
      patients with a fractured hip. The objective was to devise a simple and effective
      method of random allocation concealment suitable for use by paramedics while in
      the emergency prehospital setting. METHODS: Scratchcards were produced using
      scratch-off silver stickers which concealed the trial arm allocation. Paramedics
      were each allocated a unique range of consecutive numbers, used as both the
      scratchcard number and the patient's study ID. The cards were designed to allow
      the paramedic to write on the incident number, date and signature. A small
      envelope holding the cards was prepared for each paramedic. The study took place
      between 28 June 2016 and 31 July 2017 in the Swansea area. RESULTS: Nineteen
      trial paramedics used 71 scratchcards throughout the study and reported no
      problems randomly allocating patients using the scratchcards. Five protocol
      deviations were reported in relation to scratchcard use. On auditing the
      scratchcards, all unused cards were located, and no evidence of tampering with
      the silver panel was found. CONCLUSION: Paramedics can use scratchcards as a
      method of randomly allocating patients in trials in prehospital care. In the
      future, a method that allows only the top card to be selected and a more
      protective method of storing the cards should be used. Scratchcards can be
      considered for wider use in RCTs in the emergency prehospital setting. TRIAL
      REGISTRATION NUMBER: ISRCTN60065373; Post-results.

PMID- 30209075
TI  - Hyperbilirubinemia, Phototherapy, and Childhood Asthma.
AB  - OBJECTIVES: Our aim was to quantify the associations of both hyperbilirubinemia
      and phototherapy with childhood asthma using a population-based cohort with total
      serum bilirubin (TSB) levels. METHODS: Retrospective cohort study of infants born
      at >=35 weeks' gestation in the Kaiser Permanente Northern California health
      system (n = 109 212) from 2010 to 2014. Cox models were used to estimate hazard
      ratios (HRs) for a diagnosis of asthma. RESULTS: In the study, 16.7% of infants
      had a maximum TSB level of >=15 mg/dL, 4.5% of infants had a maximum TSB level of
      >=18 mg/dL, and 11.5% of infants received phototherapy. Compared with children
      with a maximum TSB level of 3 to 5.9 mg/L, children with a TSB level of 9 to 11.9
      mg/dL, 12 to 14.9 mg/dL, and 15 to 17.9 mg/dL were at an increased risk for
      asthma (HR: 1.22 [95% confidence interval (CI): 1.11-1.3], HR: 1.18 [95% CI: 1.08
      1.29], and HR: 1.30 [95% CI: 1.18-1.43], respectively). Children with a TSB level
      of >=18 mg/dL were not at an increased risk for asthma (HR: 1.04; 95% CI: 0.90
      1.20). In propensity-adjusted analyses, phototherapy was not associated with
      asthma (HR: 1.07; 95% CI: 0.96-1.20). CONCLUSIONS: Modest levels of
      hyperbilirubinemia were associated with an increased risk of asthma, but an
      association was not seen at higher levels. No dose-response relationship was
      seen. Using phototherapy to prevent infants from reaching these modest TSB levels
      is unlikely to be protective against asthma.

PMID- 30209077
TI  - Are Cyst-Associated Macrophages in Polycystic Kidney Disease the Equivalent to
      TAMs in Cancer?

PMID- 30209076
TI  - Enzymatic synthesis and chemical inversion provide both enantiomers of bioactive
      epoxydocosapentaenoic acids.
AB  - Epoxy PUFAs are endogenous cytochrome P450 (P450) metabolites of dietary PUFAs.
      Although these metabolites exert numerous biological effects, attempts to study
      their complex biology have been hampered by difficulty in obtaining the epoxides
      as pure regioisomers and enantiomers. To remedy this, we synthesized 19,20- and
      16,17-epoxydocosapentaenoic acids (EDPs) (the two most abundant EDPs in vivo) by
      epoxidation of DHA with WT and the mutant (F87V) P450 enzyme BM3 from Bacillus
      megaterium WT epoxidation yielded a 4:1 mixture of 19,20:16,17-EDP exclusively as
      (S,R) enantiomers. Epoxidation with the mutant (F87V) yielded a 1.6:1 mixture of
      19,20:16,17-EDP; the 19,20-EDP fraction was ~9:1 (S,R):(R,S), but the 16,17-EDP
      was exclusively the (S,R) enantiomer. To access the (R,S) enantiomers of these
      EDPs, we used a short (four-step) chemical inversion sequence, which utilizes 2
      (phenylthio)ethanol as the epoxide-opening nucleophile, followed by mesylation of
      the resulting alcohol, oxidation of the thioether moiety, and base-catalyzed
      elimination. This short synthesis cleanly converts the (S,R)-epoxide to the (R,S)
      epoxide without loss of enantiopurity. This method, also applicable to
      eicosapentaenoic acid and arachidonic acid, provides a simple, cost-effective
      procedure for accessing larger amounts of these metabolites.

PMID- 30209079
TI  - Accuracy and precision of transcutaneous carbon dioxide monitoring: a systematic
      review and meta-analysis.
AB  - BACKGROUND: Transcutaneous carbon dioxide (TcCO2) monitoring is a non-invasive
      alternative to arterial blood sampling. The aim of this review was to determine
      the accuracy and precision of TcCO2 measurements. METHODS: Medline and EMBASE
      (2000-2016) were searched for studies that reported on a measurement of PaCO2
      that coincided with a measurement of TcCO2. Study selection and quality
      assessment (using the revised Quality Assessment of Diagnostic Accuracy Studies
      tool (QUADAS-2)) were performed independently. The Grading Quality of Evidence
      and Strength of Recommendation approach was used to summarise the strength of the
      body of evidence. Pooled estimates of the mean bias between TcCO2 and PaCO2 and
      limits of agreement with outer 95% CIs (termed population limits of agreement)
      were calculated. RESULTS: The mean bias was -0.1 mm Hg and the population limits
      of agreement were -15 to 15 mm Hg for 7021 paired measurements taken from 2817
      participants in 73 studies, which was outside of the clinically acceptable range
      (7.5 mm Hg). The lowest PaCO2 reported in the studies was 18 mm Hg and the
      highest was 103 mm Hg. The major sources of inconsistency were sensor location
      and temperature. The population limits of agreement were within the clinically
      acceptable range across 3974 paired measurements from 1786 participants in 44
      studies that applied the sensor to the earlobe using the TOSCA and Sentec devices
      (-6 to 6 mm Hg). CONCLUSION: There are substantial differences between TcCO2 and
      PaCO2 depending on the context in which this technology is used. TcCO2 sensors
      should preferentially be applied to the earlobe and users should consider setting
      the temperature of the sensor higher than 42 degrees C when monitoring at other
      sites. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO; CRD42017057450.

PMID- 30209078
TI  - Mcp1 Promotes Macrophage-Dependent Cyst Expansion in Autosomal Dominant
      Polycystic Kidney Disease.
AB  - BACKGROUND: In patients with autosomal dominant polycystic kidney disease
      (ADPKD), most of whom have a mutation in PKD1 or PKD2, abnormally large numbers
      of macrophages accumulate around kidney cysts and promote their growth. Research
      by us and others has suggested that monocyte chemoattractant protein-1 (Mcp1) may
      be a signal for macrophage-mediated cyst growth. METHODS: To define the role of
      Mcp1 and macrophages in promoting cyst growth, we used mice with inducible
      knockout of Pkd1 alone (single knockout) or knockout of both Pkd1 and Mcp1
      (double knockout) in the murine renal tubule. Levels of Mcp1 RNA expression were
      measured in single-knockout mice and controls. RESULTS: In single-knockout mice,
      upregulation of Mcp1 precedes macrophage infiltration. Macrophages accumulating
      around nascent cysts (0-2 weeks after induction) are initially proinflammatory
      and induce tubular cell injury with morphologic flattening, oxidative DNA damage,
      and proliferation-independent cystic dilation. At 2-6 weeks after induction,
      macrophages switch to an alternative activation phenotype and promote further
      cyst growth because of an additional three-fold increase in tubular cell
      proliferative rates. In double-knockout mice, there is a marked reduction in Mcp1
      expression and macrophage numbers, resulting in less initial tubular cell injury,
      slower cyst growth, and improved renal function. Treatment of single-knockout
      mice with an inhibitor to the Mcp1 receptor Ccr2 partially reproduced the
      morphologic and functional improvement seen with Mcp1 knockout. CONCLUSIONS: Mcp1
      is upregulated after knockout of Pkd1 and promotes macrophage accumulation and
      cyst growth via both proliferation-independent and proliferation-dependent
      mechanisms in this orthologous mouse model of ADPKD.

PMID- 30209080
TI  - Combined Analysis of Antigen Presentation and T-cell Recognition Reveals
      Restricted Immune Responses in Melanoma.
AB  - The quest for tumor-associated antigens (TAA) and neoantigens is a major focus of
      cancer immunotherapy. Here, we combine a neoantigen prediction pipeline and human
      leukocyte antigen (HLA) peptidomics to identify TAAs and neoantigens in 16 tumors
      derived from seven patients with melanoma and characterize their interactions
      with their tumor-infiltrating lymphocytes (TIL). Our investigation of the
      antigenic and T-cell landscapes encompassing the TAA and neoantigen signatures,
      their immune reactivity, and their corresponding T-cell identities provides the
      first comprehensive analysis of cancer cell T-cell cosignatures, allowing us to
      discover remarkable antigenic and TIL similarities between metastases from the
      same patient. Furthermore, we reveal that two neoantigen-specific clonotypes
      killed 90% of autologous melanoma cells, both in vitro and in vivo, showing that
      a limited set of neoantigen-specific T cells may play a central role in melanoma
      tumor rejection. Our findings indicate that combining HLA peptidomics with
      neoantigen predictions allows robust identification of targetable neoantigens,
      which could successfully guide personalized cancer immunotherapies.Significance:
      As neoantigen targeting is becoming more established as a powerful therapeutic
      approach, investigating these molecules has taken center stage. Here, we show
      that a limited set of neoantigen-specific T cells mediates tumor rejection,
      suggesting that identifying just a few antigens and their corresponding T-cell
      clones could guide personalized immunotherapy. Cancer Discov; 8(11); 1366-75.
      (c)2018 AACR. This article is highlighted in the In This Issue feature, p. 1333.

PMID- 30209081
TI  - Multiple Routes to Oncogenesis Are Promoted by the Human Papillomavirus-Host
      Protein Network.
AB  - We have mapped a global network of virus-host protein interactions by
      purification of the complete set of human papillomavirus (HPV) proteins in
      multiple cell lines followed by mass spectrometry analysis. Integration of this
      map with tumor genome atlases shows that the virus targets human proteins
      frequently mutated in HPV- but not HPV+ cancers, providing a unique opportunity
      to identify novel oncogenic events phenocopied by HPV infection. For example, we
      find that the NRF2 transcriptional pathway, which protects against oxidative
      stress, is activated by interaction of the NRF2 regulator KEAP1 with the viral
      protein E1. We also demonstrate that the L2 HPV protein physically interacts with
      the RNF20/40 histone ubiquitination complex and promotes tumor cell invasion in
      an RNF20/40-dependent manner. This combined proteomic and genetic approach
      provides a systematic means to study the cellular mechanisms hijacked by virally
      induced cancers.Significance: In this study, we created a protein-protein
      interaction network between HPV and human proteins. An integrative analysis of
      this network and 800 tumor mutation profiles identifies multiple oncogenesis
      pathways promoted by HPV interactions that phenocopy recurrent mutations in
      cancer, yielding an expanded definition of HPV oncogenic roles. Cancer Discov;
      8(11); 1474-89. (c)2018 AACR. This article is highlighted in the In This Issue
      feature, p. 1333.

PMID- 30209082
TI  - Prevalence and causes of vision loss in North Africa and Middle East in 2015:
      magnitude, temporal trends and projections.
AB  - BACKGROUND: To assess the prevalence and causes of vision impairment in North
      Africa and the Middle East (NAME) from 1990 to 2015 and to forecast projections
      for 2020. METHODS: Based on a systematic review of medical literature, the
      prevalence of blindness (presenting visual acuity (PVA) <3/60 in the better eye),
      moderate and severe vision impairment (MSVI; PVA <6/18 but >=3/60) and mild
      vision impairment (PVA <6/12 but >=6/18) was estimated for 2015 and 2020.
      RESULTS: The age-standardised prevalence of blindness and MSVI for all ages and
      genders decreased from 1990 to 2015, from 1.72 (0.53-3.13) to 0.95% (0.32%
      1.71%), and from 6.66 (3.09-10.69) to 4.62% (2.21%-7.33%), respectively, with
      slightly higher figures for women than men. Cataract was the most common cause of
      blindness in 1990 and 2015, followed by uncorrected refractive error. Uncorrected
      refractive error was the leading cause of MSVI in the NAME region in 1990 and
      2015, followed by cataract. A reduction in the proportions of blindness and MSVI
      due to cataract, corneal opacity and trachoma is predicted by 2020. Conversely,
      an increase in the proportion of blindness attributable to uncorrected refractive
      error, glaucoma, age-related macular degeneration and diabetic retinopathy is
      expected. CONCLUSIONS: In 2015 cataract and uncorrected refractive error were the
      major causes of vision loss in the NAME region. Proportions of vision impairment
      from cataract, corneal opacity and trachoma are expected to decrease by 2020, and
      those from uncorrected refractive error, glaucoma, diabetic retinopathy and age
      related macular degeneration are predicted to increase by 2020.

PMID- 30209085
TI  - Euthanasia and suicide.

PMID- 30209086
TI  - ?

PMID- 30209084
TI  - Prevalence and causes of vision loss in South-east Asia and Oceania in 2015:
      magnitude, temporal trends and projections.
AB  - BACKGROUND: To assess prevalence and causes of vision impairment in South-east
      Asia and Oceania regions from 1990 to 2015 and to forecast the figures for 2020.
      METHODS: Based on a systematic review of medical literature, prevalence of
      blindness (presenting visual acuity (PVA) <3/60 in the better eye), moderate and
      severe vision impairment (MSVI; PVA <6/18 but >=3/60), mild vision impairment
      (PVA <6/12 but >=6/18) and near vision impairment (>N5 or N8 in the presence of
      normal vision) were estimated for 1990, 2010, 2015 and 2020. RESULTS: The age
      standardised prevalence of blindness for all ages and both genders was higher in
      the Oceania region but lower for MSVI when comparing the subregions. The
      prevalence of near vision impairment in people>=50 years was 41% (uncertainty
      interval (UI) 18.8 to 65.9). Comparison of the data for 2015 with 2020 predicts a
      small increase in the numbers of people affected by blindness, MSVI and mild VI
      in both subregions. The numbers predicted for near VI in South-east Asia are from
      90.68 million in 2015 to 102.88 million in 2020. The main causes of blindness and
      MSVI in both subregions in 2015 were cataract, uncorrected refractive error,
      glaucoma, corneal disease and age-related macular degeneration. There was no
      trachoma in Oceania from 1990 and decreasing prevalence in South-east Asia with
      elimination predicted by 2020. CONCLUSIONS: In both regions, the main challenges
      for eye care come from cataract which remains the main cause of blindness with
      uncorrected refractive error the main cause of MSVI. The trend between 1990 and
      2015 is for a lower prevalence of blindness and MSVI in both regions.

PMID- 30209087
TI  - Radon gas.

PMID- 30209083
TI  - Prevalence and causes of vision loss in Latin America and the Caribbean in 2015:
      magnitude, temporal trends and projections.
AB  - OBJECTIVE: To estimate the prevalence and causes of blindness and vision
      impairment for distance and near in Latin America and the Caribbean (LAC) in 2015
      and to forecast trends to 2020. METHODS: A meta-analysis from a global systematic
      review of 283 cross-sectional, population-representative studies from published
      and unpublished sources from 1980 to 2014 in the Global Vision Database included
      17 published and 6 unpublished studies from LAC. RESULTS: In 2015, across LAC,
      age-standardised prevalence was 0.38% in all ages and 1.56% in those over age 50
      for blindness; 2.06% in all ages and 7.86% in those over age 50 for moderate and
      severe vision impairment (MSVI); 1.89% in all ages and 6.93% in those over age 50
      for mild vision impairment and 39.59% in all ages and 45.27% in those over 50 for
      near vision impairment (NVI). In 2015, 117.86 million persons were vision
      impaired; of those 2.34 million blind, 12.46 million with MSVI, 11.34 million
      mildly impaired and 91.72 million had NVI. Cataract is the most common cause of
      blindness. Undercorrected refractive-error is the most common cause of vision
      impairment. CONCLUSIONS: These prevalence estimates indicate that one in five
      persons across LAC had some degree of vision loss in 2015. We predict that from
      2015 to 2020, the absolute numbers of persons with vision loss will increase by
      12% to 132.33 million, while the all-age age-standardised prevalence will
      decrease for blindness by 15% and for other distance vision impairment by 8%. All
      countries need epidemiologic research to establish accurate national estimates
      and trends. Universal eye health services must be included in universal health
      coverage reforms to address disparities, fragmentation and segmentation of
      healthcare.

PMID- 30209088
TI  - Not my quality.

PMID- 30209089
TI  - Nortriptyline safer than amitriptyline?

PMID- 30209091
TI  - Reflections from a provider of medical assistance in dying.

PMID- 30209090
TI  - Kratom case report.

PMID- 30209092
TI  - Time to clarify Canada's medical assistance in dying law.

PMID- 30209093
TI  - ?

PMID- 30209095
TI  - Overdiagnosis: causes and consequences in primary health care.

PMID- 30209097
TI  - ?

PMID- 30209096
TI  - Second-generation antipsychotics in children: Risks and monitoring needs.
AB  - Question A 10-year-old male patient presented to my clinic with irritability
      associated with autism spectrum disorder, and previous therapeutic efforts had
      not been successful. Treatment with quetiapine has considerably reduced
      irritability and improved his quality of life; however, the patient's mother has
      stated that her child's clothes are no longer fitting because his waist size has
      increased substantially, and that he has gained 5 kg since treatment initiation 8
      weeks ago. Should second-generation antipsychotic (SGA) treatment be stopped or
      continued, and how can these side effects be best mitigated in a family practice
      setting?Answer Use of SGAs in pediatric patients has increased in recent years,
      which has brought to light a number of worrisome metabolic side effects that
      occur in children. Owing to the efficacy of treatment, SGAs must often be
      continued despite side effects. Even if the drug has been prescribed elsewhere,
      family physicians should closely monitor these patients following the Canadian
      Alliance for Monitoring Effectiveness and Safety of Antipsychotics in Children
      guidelines. When starting an SGA, patients and their families should be educated
      on the importance of healthy eating and physical activity to preemptively
      mitigate potential side effects. Recent studies have also shown adjunctive
      metformin to have a potential role in reducing weight gain.

PMID- 30209098
TI  - Dying alone: An Indigenous man's journey at the end of life.

PMID- 30209094
TI  - Optimizing medications in older adults with cognitive impairment: Considerations
      for primary care clinicians.
AB  - OBJECTIVE: To provide primary care physicians with an approach to medication
      optimization in older adults with cognitive impairment. SOURCES OF INFORMATION:
      The approach is based on an accredited memory clinic training program developed
      by the Centre for Family Medicine Primary Care Collaborative Memory Clinic. MAIN
      MESSAGE: Dementia increases the risk of medication-related adverse events and
      adds to the complexity and challenge of providing optimal care for these older
      adults. Considerations include medication adherence, appropriate therapeutic
      targets for comorbid conditions, minimized use of medications with potentially
      adverse cognitive effects, and rational use and monitoring of cognition-enhancing
      drugs. Medication management plans must be individualized and based on goals of
      care. CONCLUSION: Primary care physicians must consider many factors in
      optimizing medications for those with cognitive impairment.

PMID- 30209099
TI  - Do PCSK9 inhibitors reduce cardiovascular events?

PMID- 30209100
TI  - Below-knee cast: Casting Immobilization Series for Primary Care.

PMID- 30209101
TI  - Reasons for requesting medical assistance in dying.
AB  - OBJECTIVE: To review the charts of people who requested medical assistance in
      dying (MAID) to examine their reasons for the request. DESIGN: Retrospective
      chart survey. SETTING: British Columbia. PARTICIPANTS: Patients who requested an
      assisted death and were assessed by 1 of 6 physicians in British Columbia during
      2016. MAIN OUTCOME MEASURES: Patients' diagnoses and reasons for requesting MAID.
      RESULTS: Data were collected from 250 assessments for MAID: 112 of the patients
      had assisted deaths, 11 had natural deaths, 35 were assessed as not eligible for
      MAID, and most of the rest were not ready. For people who had assisted deaths,
      disease-related symptoms were given as the first or second most important reason
      for requesting assisted death by 67 people (59.8%), while 59 (52.7%) gave loss of
      autonomy, 55 (49.1%) gave loss of ability to enjoy activities, and 27 (24.1%)
      gave fear of future suffering. People who were assessed as eligible but who had
      not received assisted deaths were more likely to list fear of future suffering
      (33.7% vs 7.1%) and less likely to list disease-related symptoms (17.4% vs 40.2%)
      than those who received MAID were. There was a difference in reasons for MAID
      given by people with different diagnoses; disease-related symptoms were given as
      the most important reason by 39.0% of patients with malignancies, 6.8% of
      patients with neurological diseases, and 28.9% of patients with end-organ
      failure. Loss of autonomy was given as the most important reason by 16.0% of
      patients with malignancies, 36.4% of patients with neurological diseases, and
      23.7% of patients with end-organ failure. CONCLUSION: This study shows that the
      reasons patients give for requesting an assisted death are similar to those
      reported in other jurisdictions with similar laws, but in different proportions.
      Loss of autonomy and loss of ability to enjoy activities were less common reasons
      among patients in this study compared with other jurisdictions. This might be
      related to the method of data collection, as in this study, the patients' reasons
      were recorded by physicians.

PMID- 30209102
TI  - ?

PMID- 30209103
TI  - Questionnaire instrument development in primary health care research: A plea for
      the use of Bayesian inference.

PMID- 30209106
TI  - ?

PMID- 30209105
TI  - ?

PMID- 30209104
TI  - Patient's Medical Home update.

PMID- 30209107
TI  - Celebrating all the family medicine teachers.

PMID- 30209108
TI  - ?

PMID- 30209110
TI  - ?

PMID- 30209109
TI  - ?

PMID- 30209111
TI  - Experiences and perspectives of people who pursued medical assistance in dying:
      Qualitative study in Vancouver, BC.
AB  - OBJECTIVE: To explore the experiences, wishes, fears, and beliefs of people who
      requested and were eligible for medical assistance in dying (MAID) in Canada in
      the first year after legalization. DESIGN: Qualitative study using semistructured
      interviews. SETTING: A clinic in Vancouver, BC, that provides MAID. PARTICIPANTS:
      People requesting and eligible for MAID between February 6 and December 17, 2016.
      Family and friends who were identified as the patients' primary support people
      were also interviewed. METHODS: Semistructured interviews were conducted over the
      telephone, by e-mail, or in person. The interviews were audiorecorded and
      transcribed and then analyzed using thematic qualitative analysis. The
      investigators read the transcripts and created a coding scheme to identify themes
      in the patients' experiences. The identified themes were compiled and evaluated
      in the context of what is already known based on current literature. Basic
      demographic characteristics were recorded for context. MAIN FINDINGS: Of the 23
      patients whose experiences were explored, most had a malignancy, a neurologic
      disorder, or organ failure. A main theme was that patients thought it was
      important to have autonomy and control over their own end-of-life decisions. Main
      reasons for requesting MAID were a self-perceived unacceptable quality of life,
      most commonly owing to loss of independence, mobility, ability to communicate, a
      sense of purpose, and participation in meaningful activity. Some people expressed
      fear of future suffering and future disability. Pain was seldom mentioned as a
      cause of suffering. Some participants believed they could discuss their decision
      with the people in their lives while others chose to keep it a private matter.
      Most people were not religious. CONCLUSION: The participants' reasons for
      choosing to pursue MAID were consistent with those of people in other
      jurisdictions that have been studied. They felt confident in their decision to
      pursue MAID and did not have fears about the process.

PMID- 30209112
TI  - Exploring the experience of supporting a loved one through a medically assisted
      death in Canada.
AB  - OBJECTIVE: To explore the experience of family and close friends of patients
      seeking medical assistance in dying (MAID) in Canada. DESIGN: Qualitative study
      using semistructured interviews. SETTING: A clinic in Vancouver, BC, that
      provides MAID services. PARTICIPANTS: Eighteen support people for patients
      seeking MAID. METHODS: Clinic patients seeking MAID identified their primary
      support people during consultations for an assisted death evaluation. Identified
      support people were invited to participate in the study, and those who were
      interested were asked to contact the interviewers. Semistructured interviews were
      conducted, transcribed, coded, and subjected to content analysis to elucidate
      common themes. MAIN FINDINGS: All participants were supportive of their loved
      one's wish for assisted death and they provided emotional and practical support
      in preparation for MAID. Support persons talked about the journey they went
      through from their loved one's diagnosis to the MAID request to the actual death.
      Some were initially opposed but changed their minds after seeing the suffering
      their loved ones endured. The time before the assisted death involved saying
      goodbye and, for some, ceremonial rituals (celebration of life, poems, singing,
      etc). Those interviewed after their loved one's assisted death found the death
      peaceful and reported that it offered advantages compared with natural death in
      their loved one's individual circumstances. CONCLUSION: This study provides
      insight into experiences of support people coping with a loved one who is seeking
      or has sought MAID in the context of a country unfamiliar with the legal process
      of a planned and hastened death. Participants were supportive of their loved
      one's wishes for assistance in death to end suffering and found the process to be
      peaceful overall.

PMID- 30209113
TI  - Providing medical assistance in dying: Practice perspectives.
AB  - OBJECTIVE: To explore the experiences of the first cohort of physicians to offer
      medical assistance in dying (MAID) in British Columbia. DESIGN: Qualitative study
      using semistructured, one-on-one interviews. SETTING: British Columbia.
      PARTICIPANTS: Eight physicians who offered MAID in British Columbia in 2016.
      METHODS: The physicians were interviewed by telephone or by e-mail between 4 and
      6 months after MAID was made legal in Canada, with follow-up in January 2017.
      Interviews were audiorecorded, transcribed, and analyzed through qualitative
      thematic analysis. MAIN FINDINGS: Participants believed that MAID was rewarding
      and satisfying work. They explained that some of the structural and emotional
      challenges related to providing MAID included the following: the refusal of faith
      based institutions to provide information about MAID to patients, as well as
      their refusal to allow assessments or deaths to occur on site; having to deny
      MAID to patients who did not qualify for it; disagreements with colleagues who
      did not support the provision of MAID; dealing with the grief of family and
      friends who were present at the death; and feeling like they were always on call.
      While a few participants thought that the legislative restrictions of Bill C-14
      were appropriate in the beginning when MAID was first available in Canada, most
      would like to see changes to the legislation to make it more aligned with the
      intent of the Carter decision, including broadening the eligibility criteria to
      include mature minors and people with advanced psychiatric diagnoses, having the
      ability to honour advance directives, and removing the requirement of death being
      in the reasonably foreseeable future for patients with grievous and irremediable
      conditions. CONCLUSION: Physicians in this study explained that providing MAID is
      rewarding work; however, there are many challenges that complicate their ability
      to offer MAID to patients. The current MAID legislation in Canada should be
      updated to better serve the needs of patients.

PMID- 30209114
TI  - Exploring family medicine preceptor and resident perceptions of medical
      assistance in dying and desires for education.
AB  - OBJECTIVE: To examine the perspectives of family medicine preceptors and
      residents, including their interest and intent to participate in and their
      knowledge and willingness to teach or learn about medical assistance in dying
      (MAID). DESIGN: Two anonymous surveys were distributed via e-mail using a Dillman
      approach to residents and preceptors. Responses were collected between August 23
      and November 29, 2016. Data were analyzed using descriptive and inferential
      statistics. SETTING: The large, 4-site Queen's University family medicine
      residency program in southeastern Ontario. PARTICIPANTS: A total of 71 preceptors
      and 62 residents. MAIN OUTCOME MEASURES: Physician and resident knowledge of and
      experience, comfort, and confidence with MAID; willingness to participate in
      MAID; perspectives on the effect of MAID on team relationships; and the
      importance, desired content, and delivery of MAID education. RESULTS: Overall,
      45.2% of preceptors and 33.3% of residents responded. A low proportion of both
      preceptors and residents felt competent or comfortable discussing and exploring
      MAID with a patient, with preceptors feeling significantly more competent and
      comfortable than residents (P < .001 and P < .01, respectively). Paradoxically,
      significantly more residents than preceptors were willing to be part of a
      clinical team providing MAID through oral or intravenous routes (P < .001). In
      spite of this willingness to be involved, significantly fewer residents felt safe
      discussing personal perspectives on MAID in various clinical environments (P <
      .001). Most participants from both groups believed it was important to include
      MAID in the core family medicine residency curriculum and identified specific
      curriculum content and delivery strategies. CONCLUSION: Family medicine
      preceptors and residents are willing and want to learn about MAID. Our research
      demonstrates a need to integrate MAID into the family medicine residency
      curriculum, with faculty development and continuing professional development for
      preceptors.

PMID- 30209116
TI  - Leopold and his request for medical assistance in dying.

PMID- 30209115
TI  - Snapshot of the primary care waiting room: Informing practice redesign to align
      with the Patient's Medical Home model.
AB  - OBJECTIVE: To describe the demographic characteristics, health, and health care
      experiences of adult patients in primary care waiting rooms in Quebec, and to
      determine which pillars of the Patient's Medical Home (PMH) are a priority to
      align primary care practices with the PMH model. DESIGN: Baseline survey of a
      prospective cohort study using self-administered on-site and mailed
      questionnaires. SETTING: Twelve primary care clinics within the geographic
      boundaries of 4 local health care networks in metropolitan, urban, rural, and
      remote settings in Quebec. PARTICIPANTS: A total of 1029 adult patients aged
      between 25 and 75 who were selected during a 1-week period in the 12 primary care
      clinics; 789 returned questionnaires. MAIN OUTCOME MEASURES: Patients' health
      profiles, health behaviour patterns, reasons for the visit, and health care
      experiences. RESULTS: In this 2010 snapshot, 66.8% of patients waited longer than
      2 weeks for their appointment, 71.0% of visits were for routine or follow-up
      care, and longer wait times and patient multimorbidity correlated with more
      reasons for the visit. After the visit, most patients reported being able to
      express their most important needs and that the doctor listened well; however,
      only 28.1% reported that the doctor had explored whether the recommendations
      would be realistic for them, and only 18.0% indicated that the doctor had
      explored the personal or family dimensions that affected their health. Among all
      patients, 56.9% reported having at least 3 chronic conditions (multimorbidity),
      and 30.3% reported having high or moderate levels of psychological distress. When
      describing their financial status, 30.7% of patients indicated it was "poor to
      squeezed or tight." Slightly more than half of patients did not have
      complementary private health insurance to cover costs of psychological services.
      CONCLUSION: In this study, the 4 priority pillars for practices to align with the
      PMH were timely access, team-based care, comprehensive care, and a patient
      centred approach. Widespread implementation of advanced access is an urgent
      priority in light of persisting difficulties in timely access. Team-based and
      comprehensive care are needed to address the high prevalence of multimorbidity
      and psychological distress and to support health behaviour change. Finally, the
      patient-centred approach needs to underpin every care encounter.

PMID- 30209118
TI  - Transferrin receptor 2 is a potential novel therapeutic target for beta
      thalassemia: evidence from a murine model.
AB  - beta-thalassemias are genetic disorders characterized by anemia, ineffective
      erythropoiesis, and iron overload. Current treatment of severe cases is based on
      blood transfusion and iron chelation or allogeneic bone marrow (BM)
      transplantation. Novel approaches are explored for nontransfusion-dependent
      patients (thalassemia intermedia) who develop anemia and iron overload. Here, we
      investigated the erythropoietin (EPO) receptor partner, transferrin receptor 2
      (TFR2), as a novel potential therapeutic target. We generated a murine model of
      thalassemia intermedia specifically lacking BM Tfr2: because their erythroid
      cells are more susceptible to EPO stimulation, mice show improved erythropoiesis
      and red blood cell morphology as well as partial correction of anemia and iron
      overload. The beneficial effects become attenuated over time, possibly due to
      insufficient iron availability to sustain the enhanced erythropoiesis. Germ line
      deletion of Tfr2, including haploinsufficiency, had a similar effect in the
      thalassemic model. Because targeting TFR2 enhances EPO-mediated effects
      exclusively in cells expressing both receptors, this approach may have advantages
      over erythropoiesis-stimulating agents in the treatment of other anemias.

PMID- 30209119
TI  - How I treat breast implant-associated anaplastic large cell lymphoma.
AB  - Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a recently
      described form of T-cell non-Hodgkin lymphoma now formally recognized by the
      World Health Organization classification of lymphoid neoplasms. The disease most
      often presents with a delayed seroma around the breast implant, almost
      exclusively with a textured surface, and manifests with breast pain, swelling or
      asymmetry, capsular contracture, but can also present with a breast mass, and
      lymph node involvement. The prognosis of BIA-ALCL is favorable compared with many
      other subtypes of systemic T-cell lymphoma; however, unlike other non-Hodgkin
      lymphomas, complete surgical excision for localized disease is an important part
      of the management of these patients. In this paper, we share our recommendations
      for a multidisciplinary team approach to the diagnosis, workup, and treatment of
      BIA-ALCL in line with consensus guidelines by the National Comprehensive Cancer
      Network.

PMID- 30209117
TI  - Effects of Supplemental Calcium and Vitamin D on Expression of Toll-Like
      Receptors and Phospho-IKKalpha/beta in the Normal Rectal Mucosa of Colorectal
      Adenoma Patients.
AB  - Chronic inflammation in the colorectum, a significant contributor to colorectal
      carcinogenesis, can be triggered by the activation of proinflammatory signaling
      pathways such as those initiated by Toll-like receptors (TLR) and nuclear factor
      kappaB (NF-kappaB). Although experimental evidence supports calcium and vitamin D
      potentially modifying these proinflammatory pathways in the colorectum, human
      data in these regards are scarce. We investigated supplemental calcium (1,200 mg
      daily) and/or vitamin D3 (1,000 IU daily) effects on inflammatory signaling
      pathway-related biomarkers in a subset of 105 participants from a colorectal
      adenoma recurrence chemoprevention clinical trial. We assessed expression of TLR4
      and TLR5, which recognize the bacterial components lipopolysaccharides and
      flagellin, respectively, and phospho-IKKalpha/beta (pIKKalpha/beta), a biomarker
      of inflammation, in the normal-appearing rectal crypt epithelium and stroma using
      standardized, automated immunohistochemistry and quantitative image analysis.
      Following 1 year of treatment, TLR4, TLR5, and pIKKalpha/beta expression in the
      rectal mucosa did not statistically significantly change with vitamin D or
      calcium supplementation, taken alone or in combination. Several baseline
      participant characteristics, including body mass index, history of sessile
      serrated adenomas, high red/processed meat intake, and high levels of rectal
      epithelial cell proliferation (as measured by MIB-1/Ki-67), were associated with
      higher baseline expression of TLRs or pIKKalpha/beta. Our findings suggest that
      vitamin D and calcium may have no substantial effect on the investigated
      biomarkers. However, several modifiable lifestyle factors may be associated with
      TLRs and pIKKalpha/beta expression in the normal rectal mucosa, supporting their
      future investigation as potentially treatable, preneoplastic risk factors for
      colorectal neoplasms. Cancer Prev Res; 11(11); 707-16. (c)2018 AACR.

PMID- 30209120
TI  - Murine pre-B-cell ALL induces T-cell dysfunction not fully reversed by
      introduction of a chimeric antigen receptor.
AB  - Adoptive transfer of patient-derived T cells modified to express chimeric antigen
      receptors (CARTs) has demonstrated dramatic success in relapsed/refractory pre-B
      cell acute lymphoblastic leukemia (ALL), but response and durability of remission
      requires exponential CART expansion and persistence. Tumors are known to affect T
      cell function, but this has not been well studied in ALL and in the context of
      chimeric antigen receptor (CAR) expression. Using TCF3/PBX1 and MLL-AF4-driven
      murine ALL models, we assessed the impact of progressive ALL on T-cell function
      in vivo. Vaccines protect against TCF3/PBX1.3 but were ineffective when
      administered after leukemia injection, suggesting immunosuppression induced early
      during ALL progression. T cells from leukemia-bearing mice exhibited increased
      expression of inhibitory receptors, including PD1, Tim3, and LAG3, and were
      dysfunctional following adoptive transfer in a model of T-cell receptor (TCR)
      dependent leukemia clearance. Although expression of inhibitory receptors has
      been linked to TCR signaling, pre-B-cell ALL induced inhibitory receptor
      expression, at least in part, in a TCR-independent manner. Finally, introduction
      of a CAR into T cells generated from leukemia-bearing mice failed to fully
      reverse poor in vivo function.

PMID- 30209121
TI  - B-cell receptor-mediated NFATc1 activation induces IL-10/STAT3/PD-L1 signaling in
      diffuse large B-cell lymphoma.
AB  - Knowledge of programmed death ligand 1 (PD-L1) expression and its regulation in B
      cell lymphoma cells is limited. Investigating mechanisms that control PD-L1
      expression in B-cell lymphoma cells might identify biomarkers that predict the
      efficacy of immunotherapy with anti-programmed death-1/PD-L1 antibodies. In
      addition, identification of mechanisms that regulate PD-L1 may identify molecules
      that can be targeted to improve the clinical efficacy of immune checkpoint
      inhibitors. In this study, we used proteomic approaches and patient-derived B
      cell lymphoma cell lines to investigate mechanisms that regulate PD-L1
      expression. We found that PD-L1 expression, particularly in nongerminal center B
      cell-derived diffuse large B-cell lymphoma (DLBCL), is controlled and regulated
      by several interactive signaling pathways, including the B-cell receptor (BCR)
      and JAK2/STAT3 signaling pathways. We found that that BCR-mediated NFATc1
      activation upregulates IL-10 chemokine expression in PD-L1+ B-cell lymphoma
      cells. Released IL-10 activates the JAK2/STAT3 pathway, leading to STAT3-induced
      PD-L1 expression. IL-10 antagonist antibody abrogates IL-10/STAT3 signaling and
      PD-L1 protein expression. We also found that BCR pathway inhibition by BTK
      inhibitors (ibrutinib, acalabrutinib, and BGB-3111) blocks NFATc1 and STAT3
      activation, thereby inhibiting IL-10 and PD-L1 expression. Finally, we validated
      the PD-L1 signaling network in 2 primary DLBCL cohorts consisting of 428 and 350
      cases and showed significant correlations among IL-10, STAT3, and PD-L1. Thus,
      our findings reveal a complex signaling network regulating PD-L1 expression in B
      cell lymphoma cells and suggest that PD-L1 expression can be modulated by small
      molecule inhibitors to potentiate immunotherapies.

PMID- 30209122
TI  - Cardiovascular risk model performance in women with and without hypertensive
      disorders of pregnancy.
AB  - OBJECTIVES: Compare the predictive performance of Framingham Risk Score (FRS),
      Pooled Cohort Equations (PCEs) and Systematic COronary Risk Evaluation (SCORE)
      model between women with and without a history of hypertensive disorders of
      pregnancy (hHDP) and determine the effects of recalibration and refitting on
      predictive performance. METHODS: We included 29 751 women, 6302 with hHDP and 17
      369 without. We assessed whether models accurately predicted observed 10-year
      cardiovascular disease (CVD) risk (calibration) and whether they accurately
      distinguished between women developing CVD during follow-up and not
      (discrimination), separately for women with and without hHDP. We also
      recalibrated (updating intercept and slope) and refitted (recalculating
      coefficients) the models. RESULTS: Original FRS and PCEs overpredicted 10-year
      CVD risks, with expected:observed (E:O) ratios ranging from 1.51 (for FRS in
      women with hHDP) to 2.29 (for PCEs in women without hHDP), while E:O ratios were
      close to 1 for SCORE. Overprediction attenuated slightly after recalibration for
      FRS and PCEs in both hHDP groups. Discrimination was reasonable for all models,
      with C-statistics ranging from 0.70-0.81 (women with hHDP) and 0.72-0.74 (women
      without hHDP). C-statistics improved slightly after refitting 0.71-0.83 (with
      hHDP) and 0.73-0.80 (without hHDP). The E:O ratio of the original PCE model was
      statistically significantly better in women with hHDP compared with women without
      hHDP. CONCLUSIONS: SCORE performed best in terms of both calibration and
      discrimination, while FRS and PCEs overpredicted risk in women with and without
      hHDP, but improved after recalibrating and refitting the models. No separate
      model for women with hHDP seems necessary, despite their higher baseline risk.

PMID- 30209124
TI  - Coronary artery bypass graft versus percutaneous coronary intervention in acute
      heart failure.
AB  - OBJECTIVE: Myocardial ischaemia is a leading cause of acute heart failure (AHF).
      However, optimal revascularisation strategies in AHF are unclear. We aimed to
      compare two revascularisation strategies, coronary artery bypass graft (CABG) and
      percutaneous coronary intervention (PCI), in patients with AHF. METHODS: Among
      5625 consecutive patients enrolled prospectively in the Korean Acute Heart
      Failure registry from March 2011 to February 2014, 717 patients who received CABG
      or PCI during the index hospitalisation for AHF were included in this analysis.
      We compared adverse outcomes (death, rehospitalisation for HF aggravation or
      cardiovascular causes, ischaemic stroke and a composite outcome of death and
      rehospitalisation for HF aggravation or cardiovascular causes) with the use of
      propensity score matching. RESULTS: For the propensity score-matched cohort with
      190 patients, CABG had a lower risk of all-cause mortality than PCI (83 vs 147
      deaths per 1000 patient-years; HR 0.57, 95% CI 0.34 to 0.96, p=0.033) during the
      median follow-up of 4 years. There was also a trend towards lower rates of
      rehospitalisation due to cardiovascular events or HF aggravation. Subgroup
      analysis revealed that the adverse outcomes were significantly lower in the CABG
      group than in PCI group, especially in patients with old age, three-vessel
      diseases, significant proximal left anterior descending artery disease and those
      without left main vessel disease or chronic total occlusion. CONCLUSIONS:
      Compared with PCI, CABG is associated with significant lower all-cause mortality
      in patients with AHF. Further studies should evaluate proper revascularisation
      strategies in AHF. CLINICAL TRIAL REGISTRATION: NCT01389843; Results.

PMID- 30209123
TI  - Digoxin and clinical outcomes in the Global Rheumatic Heart Disease Registry.
AB  - OBJECTIVE: Digoxin is widely used in patients with rheumatic heart disease (RHD)
      despite a lack of data on its impact on clinical outcomes. We aimed to determine
      the association of digoxin use on clinical outcomes in patients with RHD.
      METHODS: We performed a retrospective analysis of the association of digoxin use
      with mortality at 2 years in a large RHD registry. Secondary outcomes were
      recurrent heart failure (HF) and hospitalisation for any cause. We assessed
      associations using multivariable logistic regression in the entire cohort and in
      subgroups of patients with atrial fibrillation (AF) and HF. We also estimated
      average treatment effects from propensity-adjusted analyses using inverse
      probability treatment weighting. RESULTS: Information on digoxin use at baseline
      was available for 98.7% (3298/3343) of patients. In the overall population,
      digoxin was significantly associated with mortality (OR 1.63, 95% CI 1.30 to
      2.04, p<0.0001) and recurrent HF (OR 1.48, 95% CI 1.07 to 2.04, p=0.019). On
      propensity-weighted analyses, this effect was markedly attenuated (OR 1.05, 95%
      CI 1.01 to 1.09, p=0.005). Patients in sinus rhythm without HF had a higher
      propensity-adjusted odds of death with digoxin use (OR 1.06, 95% CI 1.01 to 1.12,
      p=0.015), but those with both AF and HF had lower mortality (OR 0.88, 95% CI 0.80
      to 0.98, p=0.019). CONCLUSION: Digoxin use is associated with higher mortality in
      patients with RHD, but this is greatly attenuated on propensity adjustment,
      indicating the presence of substantial treatment bias. The adjusted estimates may
      therefore not be reliable, and large randomised trials are needed to determine
      the true effect of digoxin in patients with RHD.

PMID- 30209125
TI  - Discharge against medical advice after hospitalisation for acute myocardial
      infarction.
AB  - BACKGROUND: Discharge against medical advice (AMA) occurs infrequently but is
      associated with poor outcomes. There are limited descriptions of discharges AMA
      in national cohorts of patients with acute myocardial infarction (AMI). This
      study aims to evaluate discharge AMA in AMI and how it affects readmissions.
      METHODS: We conducted a cohort study of patients with AMI in USA in the
      Nationwide Readmission Database who were admitted between the years 2010 and
      2014. Descriptive statistics were presented for variables according to discharge
      home or AMA. The primary end point was all-cause 30-day unplanned readmissions
      and their causes. RESULTS: 2663 019 patients were admitted with AMI of which
      10.3% (n=162 070) of 1569 325 patients had an unplanned readmission within 30
      days. The crude rate of discharge AMA remained stable between 2010 and 2014 at
      1.5%. Discharge AMA was an independent predictor of unplanned all-cause
      readmissions (OR 2.27 95% CI 2.14 to 2.40); patients who discharged AMA had
      >twofold increased crude rate of readmission for AMI (30.4% vs 13.4%) and higher
      crude rate of admissions for neuropsychiatric reasons (3.2% vs 1.3%). After
      adjustment, discharge AMA was associated with increased odds of readmissions for
      AMI (OR 3.65 95% CI 3.31 to 4.03, p<0.001). We estimate that there are 1420
      excess cases of AMI among patients who discharged AMA. CONCLUSIONS: Discharge AMA
      occurs in 1.5% of the population with AMI and these patients are at higher risk
      of early readmissions for re-infarction. Interventions should be developed to
      reduce discharge AMA in high-risk groups and initiate interventions to avoid
      adverse outcomes and readmission.

PMID- 30209126
TI  - Effect of apixaban compared with warfarin on coagulation markers in atrial
      fibrillation.
AB  - OBJECTIVES: Compare the effect of apixaban and warfarin on coagulation and
      primary haemostasis biomarkers in atrial fibrillation (AF). METHODS: The
      biomarker substudy from the Apixaban for Reduction in Stroke and Other
      Thromboembolic Events in Atrial Fibrillation trial included 4850 patients with AF
      randomised to treatment with apixaban or warfarin. Sixty per cent of patients
      used vitamin K antagonist (VKA) within 7 days before randomisation. Prothrombin
      fragment 1+2 (F1+2), D-dimer, soluble CD40 ligand (sCD40L) and von Willebrand
      factor (vWF) antigen were analysed at randomisation and after 2 months of study
      treatment. RESULTS: In patients not on VKA treatment at randomisation, F1+2 and D
      dimer levels were decreased by 25% and 23%, respectively, with apixaban, and by
      59% and 38%, respectively, with warfarin (p<0.0001 for treatment differences for
      both). In patients on VKA at randomisation, F1+2 and D-dimer levels increased by
      41% and 10%, respectively, with apixaban and decreased by 37% and 11%,
      respectively, with warfarin (p<0.0001 for treatment differences for both). sCD40L
      levels were slightly increased at 2 months, regardless of VKA or randomised
      treatment. Apixaban and warfarin also both reduced vWF antigen regardless of VKA
      treatment. The efficacy (stroke) and safety (bleeding) of apixaban compared with
      warfarin was similar irrespectively of biomarker levels at 2 months. CONCLUSIONS:
      Treatment with apixaban compared with warfarin for stroke prevention in patients
      with AF was associated with less reduction in thrombin generation and fibrin
      turnover. This effect of apixaban could contribute to the clinical results where
      apixaban was superior to warfarin both in stroke prevention and in reducing
      bleeding risk. TRIAL REGISTRATION NUMBER: NCT00412984.

PMID- 30209127
TI  - Cardiac transplantation: indications, eligibility and current outcomes.

PMID- 30209129
TI  - Development and Use of an Endpoint Titration Assay To Characterize Mumps IgG
      Avidity following Measles, Mumps, and Rubella Vaccination and Wild-Type Mumps
      Infection.
AB  - Waning mumps IgG antibody and incomplete IgG avidity maturation may increase
      susceptibility to mumps virus infection in some vaccinees. To measure mumps IgG
      avidity, serum specimens serially diluted to the endpoint were incubated on a
      commercial mumps-specific IgG enzyme immunoassay and treated with the protein
      denaturant diethylamine (60 mM, pH 10). End titer avidity indices (etAIs [percent
      ratio of detected diethylamine-resistant IgG at endpoint]) were calculated.
      Unpaired serum specimens (n = 108) from 15-month-old children living in a low
      incidence setting were collected 1 month and 2 years after the first measles,
      mumps, and rubella vaccine dose (MMR1) and tested for mumps avidity. Per the
      receiver operating characteristic curve, the avidity assay is accurate (area
      under the curve, 0.994; 95% confidence interval [CI], 0.956 to 1.000), 96.5%
      sensitive (95% CI, 87.9 to 99.6%), and 92.2% specific (95% CI, 81.1 to 97.8%) at
      an etAI of 30%. When 9 sets of paired serum specimens collected 1 to 60 months
      post-MMR1 were tested for mumps and measles IgG avidity using comparable methods,
      the mumps etAI increased from 11% to 40 to 60% in 6 months. From 6 to 60 months,
      avidity was sustained at a mean etAI of 50% (95% CI, 46 to 54%), significantly
      lower (P  < 0.0001) than the mean measles etAI of 80% (95% CI, 74 to 86%). Mean
      etAIs in children 2 years post-MMR1 (n = 51), unvaccinated adults with distant
      mumps disease (n = 29), and confirmed mumps cases (n = 23) were 54, 62, and 57%,
      respectively. A mumps-specific endpoint avidity assay was developed and
      validated, and mumps avidity was determined to be generally sustained at etAIs of
      40 to 60%, reaching etAIs of >80% in some individuals.IMPORTANCE Numerous
      outbreaks of mumps have occurred in the United States among two-dose measles
      mumps-rubella (MMR)-vaccinated populations since 2006. The avidity of mumps
      specific IgG antibodies may affect susceptibility to mumps virus infection in
      some vaccinated individuals. To accurately measure mumps avidity, we developed
      and validated a mumps-specific IgG avidity assay that determines avidity at the
      endpoint titer of serially diluted serum specimens, providing results that are
      independent of IgG concentration. At low antibody titers, endpoint methods are
      considered more accurate than methods that determine avidity at a single
      dilution. We determined that 6 months after the first MMR dose, mumps IgG avidity
      is high and generally sustained at avidity indices of 40 to 60%, reaching values
      of >80% in some individuals. Additionally, 4% (4/103) of individuals had avidity
      indices of <=30% (low avidity) 2 years after vaccination. Inadequate mumps
      avidity maturation may be one factor influencing susceptibility to mumps virus
      infection among previously vaccinated or naturally infected individuals.

PMID- 30209128
TI  - Transient Nutrient Deprivation Promotes Macropinocytosis-Dependent Intracellular
      Bacterial Community Development.
AB  - Nutrient limitation restricts bacterial growth in privileged sites such as the
      middle ear. Transient heme-iron restriction of nontypeable Haemophilus influenzae
      (NTHI), the major causative agent of chronic and recurrent otitis media (OM),
      promotes new and diverse phenotypes that can influence planktonic, biofilm, and
      intracellular lifestyles of NTHI. However, the bacterial responses to nutrient
      restriction that impact intracellular fate and survival of NTHI are unknown. In
      this work, we provide evidence for the role of transient heme-iron restriction in
      promoting the formation of intracellular bacterial communities (IBCs) of NTHI
      both in vitro and in vivo in a preclinical model of OM. We show that transient
      heme-iron restriction of NTHI results in significantly increased invasion and
      intracellular populations that escape or evade the endolysosomal pathway for
      increased intracellular survival. In contrast, NTHI continuously exposed to heme
      iron traffics through the endolysosomal pathway for degradation. The use of
      pharmacological inhibitors revealed that prior heme-iron status does not appear
      to influence NTHI internalization through endocytic pathways. However, inhibition
      of macropinocytosis altered the intracellular fate of transiently restricted NTHI
      for degradation in the endolysosomal pathway. Furthermore, prevention of
      macropinocytosis significantly reduced the number of IBCs in cultured middle ear
      epithelial cells, providing evidence for the feasibility of this approach to
      reduce OM persistence. These results reveal that microenvironmental cues can
      influence the intracellular fate of NTHI, leading to new mechanisms for survival
      during disease progression.IMPORTANCE Otitis media is the most common bacterial
      infection in childhood. Current therapies are limited in the prevention of
      chronic or recurrent otitis media which leads to increased antibiotic exposure
      and represents a significant socioeconomic burden. In this study, we delineate
      the effect of nutritional limitation on the intracellular trafficking pathways
      used by nontypeable Haemophilus influenzae (NTHI). Moreover, transient limitation
      of heme-iron led to the development of intracellular bacterial communities that
      are known to contribute to persistence and recurrence in other diseases. New
      approaches for therapeutic interventions that reduce the production of
      intracellular bacterial communities and promote trafficking through the
      endolysosomal pathway were revealed through the use of pharmacological inhibition
      of macropinocytosis. This work demonstrates the importance of an intracellular
      niche for NTHI and provides new approaches for intervention for acute, chronic,
      and recurring episodes of otitis media.

PMID- 30209131
TI  - A cation-pi interaction in a transmembrane helix of vacuolar ATPase retains the
      proton transporting arginine in a hydrophobic environment.
AB  - Vacuolar ATPases are multisubunit protein complexes that are indispensable for
      acidification and pH homeostasis in a variety of physiological processes in all
      eukaryotic cells. An arginine residue (Arg-735) in transmembrane helix 7 (TM7) of
      subunit a of the yeast ATPase is known to be essential for proton translocation.
      However, the specific mechanism of its involvement in proton transport remains to
      be determined. Arginine residues are usually assumed to "snorkel" toward the
      protein surface when exposed to a hydrophobic environment. Here, using solution
      NMR spectroscopy, molecular dynamics simulations and in vivo yeast assays, we
      obtained evidence for the formation of a transient, membrane-embedded cation-pi
      interaction in TM7 between Arg-735 and two highly conserved nearby aromatic
      residues, Tyr-733 and Trp-737. We propose a mechanism by which the transient,
      membrane-embedded cation-pi complex provides the necessary energy to keep the
      charged side chain of Arg-735 within the hydrophobic membrane. Such cation-pi
      interactions may define a general mechanism to retain charged amino acids in a
      hydrophobic membrane environment.

PMID- 30209130
TI  - Transmission of Foot-and-Mouth Disease from Persistently Infected Carrier Cattle
      to Naive Cattle via Transfer of Oropharyngeal Fluid.
AB  - Control and eradication of foot-and-mouth disease (FMD) are impeded by the
      existence of a persistent, subclinical phase of infection in ruminants; animals
      with this status are referred to as carriers. However, the epidemiological
      significance of these FMD virus (FMDV) carriers is uncertain. In the current
      investigation, the contagion associated with FMDV carrier cattle was investigated
      by exposure of susceptible cattle and pigs to oropharyngeal fluid (OPF) samples
      or tissues harvested from persistently infected cattle. Naive cattle were
      inoculated through intranasopharyngeal deposition of unprocessed OPF samples that
      had been collected from FMDV carriers at 30 days postinfection. These inoculated
      cattle developed clinical FMD, and the severity of disease they developed was
      similar to that of animals that had been infected with a high-titer inoculum. In
      contrast, pigs exposed via intraoropharyngeal inoculation of the same OPF samples
      or via ingestion of nasopharyngeal tissues harvested from the same cohort of
      persistently infected cattle did not develop FMD. These findings indicate that
      there is demonstrable contagion associated with FMDV carrier cattle despite the
      lack of evidence for transmission by direct contact. The findings presented
      herein provide novel information that should be considered for FMD risk
      mitigation strategies.IMPORTANCE Foot-and-mouth disease (FMD) is a viral disease
      of livestock with substantial impact on agricultural production and subsistence
      farming on a global scale. Control of FMD is impeded by the existence of a
      prolonged asymptomatic carrier phase during which infected cattle shed low
      quantities of infectious virus in oropharyngeal fluid (OPF) for months to years
      after infection. The epidemiological significance of FMD virus (FMDV) carriers is
      unresolved. However, the existence of the FMDV carrier state has substantial
      impact on international trade in animal products. The current investigation
      demonstrated that transfer of OPF from persistently infected FMDV carrier cattle
      to naive cattle led to fulminant clinical FMD. It was thus demonstrated that,
      although the risk for disease transmission under natural conditions is considered
      to be low, there is detectable contagion associated with FMDV carrier cattle.
      This finding is important for optimization of FMD risk mitigation strategies.

PMID- 30209134
TI  - Rab11a-Rab8a cascade regulates the formation of tunneling nanotubes through
      vesicle recycling.
AB  - Tunneling nanotubes (TNTs) are actin-enriched membranous channels enabling cells
      to communicate over long distances. TNT-like structures form between various cell
      types and mediate the exchange of different cargos, such as ions, vesicles,
      organelles and pathogens; thus, they may play a role in physiological conditions
      and diseases (e.g. cancer and infection). TNTs also allow the intercellular
      passage of protein aggregates related to neurodegenerative diseases, thus
      propagating protein misfolding. Understanding the mechanism of TNT formation is
      mandatory in order to reveal the mechanism of disease propagation and to uncover
      their physiological function. Vesicular transport controlled by the small GTPases
      Rab11a and Rab8a can promote the formation of different plasma membrane
      protrusions (filopodia, cilia and neurites). Here, we report that inhibiting
      membrane recycling reduces the number of TNT-connected cells and that
      overexpression of Rab11a and Rab8a increases the number of TNT-connected cells
      and the propagation of vesicles between cells in co-culture. We demonstrate that
      these two Rab GTPases act in a cascade in which Rab11a activation of Rab8a is
      independent of Rabin8. We also show that VAMP3 acts downstream of Rab8a to
      regulate TNT formation.

PMID- 30209133
TI  - The CDK9-cyclin T1 complex mediates saturated fatty acid-induced vascular
      calcification by inducing expression of the transcription factor CHOP.
AB  - Vascular calcification (or mineralization) is a common complication of chronic
      kidney disease (CKD) and is closely associated with increased mortality and
      morbidity rates. We recently reported that activation of the activating
      transcription factor 4 (ATF4) pathway through the saturated fatty acid (SFA)
      induced endoplasmic reticulum (ER) stress response plays a causative role in CKD
      associated vascular calcification. Here, using mouse models of CKD, we 1) studied
      the contribution of the proapoptotic transcription factor CCAAT enhancer-binding
      protein homologous protein (CHOP) to CKD-dependent medial calcification, and 2)
      we identified an additional regulator of ER stress-mediated CHOP expression.
      Transgenic mice having smooth muscle cell (SMC)-specific CHOP expression
      developed severe vascular apoptosis and medial calcification under CKD. Screening
      of a protein kinase inhibitor library identified 16 compounds, including seven
      cyclin-dependent kinase (CDK) inhibitors, that significantly suppressed CHOP
      induction during ER stress. Moreover, selective CDK9 inhibitors and CRISPR/Cas9
      mediated CDK9 reduction blocked SFA-mediated induction of CHOP expression,
      whereas inhibitors of other CDK isoforms did not. Cyclin T1 knockout inhibited
      SFA-mediated induction of CHOP and mineralization, whereas deletion of cyclin T2
      and cyclin K promoted CHOP expression levels and mineralization. Of note, the
      CDK9-cyclin T1 complex directly phosphorylated and activated ATF4. These results
      demonstrate that the CDK9-cyclin T1 and CDK9-cyclin T2/K complexes have opposing
      roles in CHOP expression and CKD-induced vascular calcification. They further
      reveal that the CDK9-cyclin T1 complex mediates vascular calcification through
      CHOP induction and phosphorylation-mediated ATF4 activation.

PMID- 30209132
TI  - The TEA domain family transcription factor TEAD4 represses murine adipogenesis by
      recruiting the cofactors VGLL4 and CtBP2 into a transcriptional complex.
AB  - The Hippo signaling pathway is known to play an important role in multiple
      physiological processes, including adipogenesis. However, whether the downstream
      components of the Hippo pathway are involved in adipogenesis remains unknown.
      Here we demonstrate that the TEA domain family (TEAD) transcription factors are
      essential for adipogenesis in murine 3T3-L1 preadipocytes. Knockdown of TEAD1-4
      stimulated adipogenesis and increased the expression of adipocyte markers in
      these cells. Interestingly, we found that the TEAD4 knockdown-mediated
      adipogenesis proceeded in a Yes-associated protein (YAP)/TAZ (Wwtr1)-independent
      manner and that adipogenesis suppression in WT cells involved formation of a
      ternary complex comprising TEAD4 and the transcriptional cofactors C-terminal
      binding protein 2 (CtBP2) and vestigial-like family member 4 (VGLL4). VGLL4 acted
      as an adaptor protein that enhanced the interaction between TEAD4 and CtBP2, and
      this TEAD4-VGLL4-CtBP2 ternary complex dynamically existed at the early stage of
      adipogenesis. Finally, we verified that TEAD4 directly targets the promoters of
      major adipogenesis transcription factors such as peroxisome proliferator
      activated receptor gamma (PPARgamma) and adiponectin, C1Q, and collagen domain
      containing (Adipoq) during adipogenesis. These findings reveal critical insights
      into the role of the TEAD4-VGLL4-CtBP2 transcriptional repressor complex in
      suppression of adipogenesis in murine preadipocytes.

PMID- 30209135
TI  - Co-expression of sperm membrane proteins CMTM2A and CMTM2B is essential for ADAM3
      localization and male fertility in mice.
AB  - Chemokines are signaling proteins that are secreted to induce chemotaxis during
      an immunological response. However, the functions of transmembrane-type chemokine
      like factor (CKLF) and the CMTM (CKLF-like MARVEL transmembrane domain
      containing) protein family remain to be determined. In this study, we focused on
      the testis-specific mouse CMTM gene cluster (Cmtm1, Cmtm2a and Cmtm2b) and
      generated CRISPR/Cas9-mediated mutant mice to examine their physiological
      functions. Although Cmtm1 mutant mice were fertile, Cmtm2a and Cmtm2b double
      mutant mice had defects in male fertility due to impaired sperm function. We
      found that co-expression of sperm membrane proteins CMTM2A and CMTM2B is required
      for male fertility and affects the localization of the sperm membrane protein
      ADAM3 in regulating sperm fertilizing ability.

PMID- 30209136
TI  - Claudin-4 reconstituted in unilamellar vesicles is sufficient to form tight
      interfaces that partition membrane proteins.
AB  - Tight junctions have been hypothesized to act as molecular fences in the plasma
      membrane of epithelial cells, helping to form differentiated apical and
      basolateral domains. While this fence function is believed to arise from the
      interaction of four-pass transmembrane claudins, the complexity of tight
      junctions has made direct evidence of their role as a putative diffusion barrier
      difficult to obtain. Here, we address this challenge by reconstituting claudin-4
      into giant unilamellar vesicles using microfluidic jetting. We find that
      reconstituted claudin-4 alone can form adhesive membrane interfaces without the
      accessory proteins that are present in vivo By controlling the molecular
      composition of the inner and outer leaflets of jetted vesicle membranes, we show
      that claudin-4-mediated interfaces can drive partitioning of extracellular
      membrane proteins with ectodomains as small as 5 nm but not of inner or outer
      leaflet lipids. Our findings indicate that homotypic interactions of claudins and
      their small size can contribute to the polarization of epithelial cells.

PMID- 30209137
TI  - Reconstitution of immune cell interactions in free-standing membranes.
AB  - The spatiotemporal regulation of signalling proteins at the contacts formed
      between immune cells and their targets determines how and when immune responses
      begin and end. Therapeutic control of immune responses therefore relies on
      thorough elucidation of the molecular processes occurring at these interfaces.
      However, the detailed investigation of each component's contribution to the
      formation and regulation of the contact is hampered by the complexities of cell
      composition and architecture. Moreover, the transient nature of these
      interactions creates additional challenges, especially in the use of advanced
      imaging technology. One approach that circumvents these problems is to establish
      in vitro systems that faithfully mimic immune cell interactions, but allow
      complexity to be 'dialled-in' as needed. Here, we present an in vitro system that
      makes use of synthetic vesicles that mimic important aspects of immune cell
      surfaces. Using this system, we began to explore the spatial distribution of
      signalling molecules (receptors, kinases and phosphatases) and how this changes
      during the initiation of signalling. The GUV/cell system presented here is
      expected to be widely applicable.

PMID- 30209138
TI  - Calcium influx mediates the chemoattractant-induced translocation of the arrestin
      related protein AdcC in Dictyostelium.
AB  - Arrestins are key adaptor proteins that control the fate of cell-surface membrane
      proteins and modulate downstream signaling cascades. The Dictyostelium discoideum
      genome encodes six arrestin-related proteins, harboring additional modules
      besides the arrestin domain. Here, we studied AdcB and AdcC, two homologs that
      contain C2 and SAM domains. We showed that AdcC - in contrast to AdcB - responds
      to various stimuli (such as the chemoattractants cAMP and folate) known to induce
      an increase in cytosolic calcium by transiently translocating to the plasma
      membrane, and that calcium is a direct regulator of AdcC localization. This
      response requires the calcium-dependent membrane-targeting C2 domain and the
      double SAM domain involved in AdcC oligomerization, revealing a mode of membrane
      targeting and regulation unique among members of the arrestin clan. AdcB shares
      several biochemical properties with AdcC, including in vitro binding to anionic
      lipids in a calcium-dependent manner and auto-assembly as large homo-oligomers.
      AdcB can interact with AdcC; however, its intracellular localization is
      insensitive to calcium. Therefore, despite their high degree of homology and
      common characteristics, AdcB and AdcC are likely to fulfill distinct functions in
      amoebae.

PMID- 30209139
TI  - Severe disease due to CCDC40 gene variants and the perils of late diagnosis in
      primary ciliary dyskinesia.
AB  - Primary ciliary dyskinesia (PCD) can manifest in the neonatal period with severe
      respiratory distress. We describe a child with PCD who presented at term with
      severe neonatal respiratory distress, persistent right upper lobe collapse and
      failure to thrive who underwent lobectomy prior to the diagnosis of PCD at the
      age of 3 years. This case report illustrates the severe spectrum of lung disease
      associated with coiled-coil domain containing protein 40 (CCDC40) gene variants
      in patients with PCD.

PMID- 30209140
TI  - Acute gastric volvulus presenting as a pseudo cardiac tamponade.

PMID- 30209141
TI  - Anaplastic large cell lymphoma in a pregnant Filipino woman successfully treated
      with prepartum and postpartum chemotherapy.
AB  - Diagnosis of a malignancy during pregnancy presents a dilemma regarding the work
      up and treatment of the patient. This report presents a 42-year-old woman on her
      23rd week of pregnancy with multiple enlarging fungating violaceous skin masses.
      Biopsy of the dominant mass revealed anaplastic large cell lymphoma. Due to the
      progressive enlargement and increase in number of the masses, the patient was
      given two cycles of chemotherapy (doxorubicin, vincristine, cyclophosphamide and
      prednisone) before delivering a live baby boy via spontaneous vaginal delivery,
      Apgar 9.9, at 37 4/7 weeks. After delivery, she completed four more cycles of
      treatment. A full-body positron emission tomography scan done 2 months after the
      last chemotherapy showed no evidence of disease. The patient is doing well with
      no evidence of disease 9 months after treatment. Her baby is thriving and has no
      gross deformities and no developmental delays.

PMID- 30209142
TI  - Invasive mediastinal aspergillosis presenting as superior vena cava syndrome in
      an immunocompetent patient.
AB  - Invasive aspergillosis (IA) is a disease of the immunocompromised with a
      predilection for the lungs, although dissemination to all organs is possible. Its
      diagnosis remains a challenge due to the absence of specific clinical
      manifestations and laboratory findings. In most cases, diagnosis is eventually
      made via invasive methods. It carries with it a high mortality due to late
      diagnosis and delayed treatment. Here, we report a fascinating case of a young,
      otherwise healthy, immunocompetent patient that presented to us with superior
      vena cava syndrome and a mediastinal mass. It was anticipated that a malignancy
      would be found on further workup but, in fact, what was eventually discovered was
      a case of IA. Our report accentuates the significance of including IA as a
      differential while diagnosing a mediastinal mass in an immunocompetent host as
      patient outcome is determined by timely diagnosis and treatment.

PMID- 30209143
TI  - Hit by the wave: a case of painful Horner's and intramural haematoma of the
      carotid.
AB  - Carotid artery dissection from rupture of the vasa vasorum is under-recognised.
      We report the case of a 60-year-old woman presenting to our hospital with a 2
      week history of right-sided headache, neck pain, unequal pupils and ptosis after
      being hit by a wave on the beach. She was diagnosed with painful Horner's
      syndrome. MR angiogram revealed dissection of the right internal carotid artery
      with an intramural haematoma without an intimal flap. A diagnosis of carotid
      artery dissection from rupture of the vasa vasorum was made. Initial
      antithrombotic (aspirin and clexane) were stopped as she was deemed a low stroke
      risk with no signs of ischaemia on MR brain. Her clinical course was uneventful
      with resolution of the intramural haematoma seen on repeat MR angiogram.

PMID- 30209144
TI  - Bladder calculi causing irreducible urogenital prolapse.
AB  - Over 200 000 surgeries for vaginal prolapse are done annually, and these are
      rarely urgent. However, when the rare event of bladder stones causes incarcerated
      procidentia, surgical intervention should not be delayed, due to unrelenting pain
      and end-organs effects. We present such a case below. A 71-year-old woman
      presents to our department with massive uterovaginal and rectal procidentia. This
      massive prolapse was found to be irreducible due to numerous dahllite stones in
      the bladder, and was causing obstructive uropathy with left-sided hydronephrosis.
      A multidisciplinary approach was necessary to surgically correct the prolapse and
      implement complete removal of all the stones. The simultaneous occurrence of
      uterovaginal prolapse, rectal prolapse and urolithiasis is uncommon. Stone
      formation is a result of chronically infected urine presenting a nidus for stone
      formation. This presentation has occurred very rarely over the last 70 years of
      the world's literature. Surgical cures can be achieved by either the vaginal or
      abdominal routes but should be treated emergently to alleviate pain, prevent
      renal impairment from obstructive uropathy and decrease infectious morbidity.

PMID- 30209146
TI  - Emphysematous pyelonephritis: outcomes of conservative management and literature
      review.
AB  - Emphysematous pyelonephritis (EPN) is a rare, necrotising infection of the renal
      parenchyma, predominantly associated with Escherichia coli infection and unless
      promptly recognised and dealt with, it carries a poor prognosis. The current
      treatment is one of antimicrobial therapies together with nephrectomy in a
      majority of patients. We report an elderly man with multiple comorbidities with a
      diagnosis of EPN whose condition improved with antimicrobial and supportive
      therapy, and no surgical intervention was required.

PMID- 30209145
TI  - Atypical case of mucous membrane pemphigoid in a 26-year-old man.
AB  - A 26-year-old Caucasian man with no previous history of chemical injury
      presenting with an inability to open his right eye was investigated for mucous
      membrane pemphigoid and treated. Examination was notable for symblepharon of the
      right eye and impetigo-like lesions on the face and neck. A biopsy with
      immunohistochemical analysis was significant for linear deposits of C3 and
      immunoglobulin G at the level of the epithelial basement membrane, confirming the
      diagnosis of mucous membrane pemphigoid. Although mucous membrane pemphigoid
      classically presents bilaterally in women in the sixth and seventh decades of
      life, our patient was a young man with unilateral cicatrising conjunctivitis who
      may have been easily misdiagnosed without a high index of suspicion. A biopsy is
      required in cases of cicatrising conjunctivitis so that even atypical cases such
      as the one presented herein can be appropriately managed.

PMID- 30209147
TI  - Enterolithiasis in posterior urethral diverticulum: an uncommon complication
      following surgery for anorectal malformation.

PMID- 30209148
TI  - Severe subcutaneous emphysema in a term neonate.

PMID- 30209149
TI  - Status dystonicus: a diagnosis delayed.
AB  - Status dystonicus, also known as the dystonic storm or dystonic crisis, is rare
      but may prove fatal due to respiratory and bulbar complications. In adults, the
      condition is rare and possibly under-reported. The lack of awareness of this
      condition among emergency and acute physicians may lead to an incorrect or
      delayed diagnosis, which should be avoided. We report a case of a 23-year-old man
      with athetoid cerebral palsy who presented to a district general hospital with
      uncontrolled dystonic movements, which were diagnosed as status dystonicus. This
      was successfully treated with intravenous clonidine, with full recovery returning
      to baseline functional state.

PMID- 30209150
TI  - When duality of renal duplexity and duplicity coexists.

PMID- 30209151
TI  - Editors' response to concerns over the publication of the Cochrane HPV vaccine
      review was incomplete and ignored important evidence of bias.

PMID- 30209152
TI  - Oral cannabinoid-rich THC/CBD cannabis extract for secondary prevention of
      chemotherapy-induced nausea and vomiting: a study protocol for a pilot and
      definitive randomised double-blind placebo-controlled trial (CannabisCINV).
AB  - INTRODUCTION: Chemotherapy-induced nausea and vomiting (CINV) remains an
      important issue for patients receiving chemotherapy despite guideline-consistent
      antiemetic therapy. Trials using delta-9-tetrahydrocannabinol-rich (THC) products
      demonstrate limited antiemetic effect, significant adverse events and flawed
      study design. Trials using cannabidiol-rich (CBD) products demonstrate improved
      efficacy and psychological adverse event profile. No definitive trials have been
      conducted to support the use of cannabinoids for this indication, nor has the
      potential economic impact of incorporating such regimens into the Australian
      healthcare system been established. CannabisCINV aims to assess the efficacy,
      safety and cost-effectiveness of adding TN-TC11M, an oral THC/CBD extract to
      guideline-consistent antiemetics in the secondary prevention of CINV. METHODS AND
      ANALYSIS: The current multicentre, 1:1 randomised cross-over, placebo-controlled
      pilot study will recruit 80 adult patients with any malignancy, experiencing CINV
      during moderate to highly emetogenic chemotherapy despite guideline-consistent
      antiemetics. Patients receive oral TN-TC11M (THC 2.5mg/CBD 2.5 mg) capsules or
      placebo capsules three times a day on day -1 to day 5 of cycle A of chemotherapy,
      followed by the alternative drug regimen during cycle B of chemotherapy and the
      preferred drug regimen during cycle C. The primary endpoint is the proportion of
      subjects attaining a complete response to CINV. Secondary and tertiary endpoints
      include regimen tolerability, impact on quality of life and health system
      resource use. The primary assessment tool is patient diaries, which are filled
      from day -1 to day 5. A subsequent randomised placebo-controlled parallel phase
      III trial will recruit a further 250 patients. ETHICS AND DISSEMINATION: The
      protocol was approved by ethics review committees for all participating sites.
      Results will be disseminated in peer-reviewed journals and at scientific
      conferences. DRUG SUPPLY: Tilray. PROTOCOL VERSION: 2.0, 9 June 2017. TRIAL
      REGISTRATION NUMBER: ANZCTR12616001036404; Pre-results.

PMID- 30209153
TI  - Relationships among perceived quality of healthcare services, satisfaction and
      behavioural intentions of international students in Kuala Lumpur, Malaysia: a
      cross-sectional study.
AB  - OBJECTIVE: The current study aimed to investigate the relationships among the
      perceived quality of healthcare services, satisfaction and behavioural intentions
      among international students in Kuala Lumpur, Malaysia. SETTING: A cross
      sectional study on public universities in Kuala Lumpur, Malaysia. PARTICIPANTS:
      All participants in this study were international students joining public
      universities in Kuala Lumpur, Malaysia. PRIMARY INDEPENDENT VARIABLE: Perceived
      quality of healthcare services measured on a SERVQUAL scale. PRIMARY DEPENDENT
      VARIABLE: Participants' satisfaction of healthcare services assessed using five
      items. SECONDARY DEPENDENT VARIABLE: Behavioural intentions measured on six
      items. RESULTS: Of the 556 international students, 500 (90%) completed the
      survey. The study used structural equation modelling (SEM) through the AMOS
      (Analysis of Moment Structures) software to analyse the data. SEM analyses showed
      that the perceived quality of healthcare services significantly and directly
      affected satisfaction, with a value of 89% and an effect size of 0.78. It also
      had a significant indirect impact on the behavioural intentions (0.78) of
      international students. The results indicated that participants' satisfaction had
      a statistically significant impact on their behavioural intentions (0.77).
      CONCLUSION: Perceived quality of care is an important driver of international
      students' satisfaction and their behavioural intention with healthcare services.
      Such relations of effects among the three investigated factors were also positive
      and significant.

PMID- 30209154
TI  - Handover training for medical students: a controlled educational trial of a pilot
      curriculum in Germany.
AB  - OBJECTIVE: The aim of this study was to implement and evaluate a newly developed
      standardised handover curriculum for medical students. We sought to assess its
      effect on students' awareness, confidence and knowledge regarding handover.
      DESIGN: A controlled educational research study. SETTING: The pilot handover
      training curriculum was integrated into a curriculum led by the Departments of
      Anesthesiology and Intensive Care (AI) at the University Hospital. It consisted
      of three modules integrated into a 4-week course of AI. Multiple types of
      handover settings namely end-of-shift, operating room/postanaesthesia recovery
      unit, intensive care unit, telephone and discharge were addressed. PARTICIPANTS:
      A total of n=147 fourth-year medical students participated in this study, who
      received either the current standard existing curriculum (no teaching of
      handover, n=78) or the curriculum that incorporated the pilot handover training
      (n=69). OUTCOME MEASURES: Paper-based questionnaires regarding attitude,
      confidence and knowledge towards handover and patient safety were used for pre
      assessment and post-assessment. RESULTS: Students showed a significant increase
      in knowledge (p<0.01) and self-confidence for the use of standardised handover
      tools (p<0.01) as well as accurate handover performance (p<0.01) among the pilot
      group. CONCLUSION: We implemented and evaluated a pilot curriculum for
      undergraduate handover training. Students displayed a significant increase in
      knowledge and self-confidence for the use of standardised handover tools and
      accuracy in handover performance. Further studies should evaluate whether the
      observed effect is sustained across time and is associated with patient benefit.

PMID- 30209155
TI  - What are the requirements for developing a successful national registry of
      auditory implants? A qualitative study.
AB  - OBJECTIVES: Hearing loss is an area of unmet need, and industry is targeting this
      field with a growing range of surgically implanted hearing devices. Currently,
      there is no comprehensive UK registry capturing data on these devices; in its
      absence, it is difficult to monitor clinical and cost-effectiveness and develop
      national policy. Recognising that developing such a registry faces considerable
      challenges, it is important to gather opinions from stakeholders and patients.
      This paper builds on our systematic review on surgical registry development and
      aims to identify the specific requirements for developing a successful national
      registry of auditory implants. DESIGN: Qualitative study. PARTICIPANTS: Data were
      collected in two ways: (1) semistructured interviews with UK professional
      stakeholders; and (2) focus groups with patients with hearing loss. The interview
      and focus group schedules were informed by our systematic review on registry
      development. Data were analysed using directed content analysis. Judges mapped
      the themes obtained against a conceptual framework developed from our systematic
      review on registry development. The conceptual framework consisted of five
      categories for successful registry development: (1) planning, (2) registry
      governance, (3) registry dataset, (4) anticipating challenges, (5) implementing
      solutions. RESULTS: Twenty-seven themes emerged from 40 semistructured interviews
      with professional stakeholders and 18 themes emerged from three patient focus
      groups. The most important factor for registry success was high rates of data
      completion. Benefits of developing a successful registry of auditory implants
      include: strengthening the evidence base and regulation of auditory implants,
      driving quality and safety improvements, increased transparency, facilitating
      patient decision-making and informing policy and guidelines development.
      CONCLUSIONS: This study identifies the requirements for developing a successful
      national registry of auditory implants, benefiting from the involvement of
      numerous professional stakeholder groups and patients with hearing loss. Our
      approach may be used internationally to inform successful registry development.

PMID- 30209156
TI  - Impact of body mass index on survival of medical patients with sepsis: a
      prospective cohort study in a university hospital in China.
AB  - OBJECTIVE: To evaluate the impact of body mass index (BMI) on survival of a
      Chinese cohort of medical patients with sepsis. DESIGN: A single-centre
      prospective cohort study conducted from May 2015 to April 2017. SETTING: A
      tertiary care university hospital in China. PARTICIPANTS: A total of 178 patients
      with sepsis admitted to the medical intensive care unit (ICU) were included. MAIN
      OUTCOME MEASURES: The primary outcome was 90-day mortality while the secondary
      outcomes were in-hospital mortality, length of ICU stay and length of hospital
      stay. RESULTS: The median age (IQR) was 78 (66-84) years old, and 77.0% patients
      were older than 65 years. The 90-day mortality was 47.2%. The in-hospital
      mortality was 41.6%, and the length of ICU stay and hospital stay were 12 (5-22)
      and 15 (9-28) days, respectively. Cox proportional hazard regression analysis
      identified that Sequential Organ Failure Assessment score (HR=1.229, p<0.001),
      Acute Physiology and Chronic Health Evaluation II score (HR=1.050, p<0.001) and
      BMI (HR=0.940, p=0.029) were all independently associated with the 90-day
      mortality. Patients were divided into four groups based on BMI (underweight 33
      (18.5%), normal 98 (55.1%), overweight 36 (20.2%) and obese 11 (6.2%)). The 90
      day mortality (66.7%, 48.0%, 36.1% and 18.2%, p=0.015) and in-hospital mortality
      (60.6%, 41.8%, 30.6% and 18.2%, p=0.027) were statistically different among the
      four groups. Differences in survival among the four groups were demonstrated by
      Kaplan-Meier survival analysis (p=0.008), with the underweight patients showing a
      lower survival rate. CONCLUSIONS: BMI was an independent factor associated with
      90-day survival in a Chinese cohort of medical patients with sepsis, with
      patients having a lower BMI at a higher risk of death.

PMID- 30209157
TI  - Screening and prevention for latent tuberculosis in immunosuppressed patients at
      risk for tuberculosis: a systematic review of clinical practice guidelines.
AB  - OBJECTIVE: Immunosuppressed individuals are at a high risk of latent tuberculosis
      infection (LTBI) and clinical practice guidelines for the screening and
      management of LTBI in at-risk patients have been developed. We assessed the
      scope, quality and consistency of clinical practice guidelines on screening for
      LTBI and the prevention of tuberculosis infection (TB) in high-risk patient
      populations. DESIGN: We conducted a systematic review of clinical practice
      guidelines. Methodological quality of these guidelines was assessed using the
      Appraisal of Guidelines for Research and Education (AGREE) II instrument. Textual
      synthesis was used to summarise and compare the recommendations. DATA SOURCES:
      Electronic databases (MEDLINE, EMBASE, PsycINFO) and guideline registries were
      searched from inception to December 2017. RESULTS: Thirty-eight guidelines were
      included. Nineteen focused on patients receiving medical immunosuppression, seven
      on transplantation, three on patients with HIV and nine were generalised across
      all at risk populations. Most guidelines (n=32, 84%) used a systematic approach
      to identify and appraise the evidence. The methodological quality of the
      guidelines varied with the overall mean AGREE II scores ranging from 35% to 80%.
      Guidelines performed poorly in terms of editorial independence (average score
      35%, range 0%-92%); however, most were robust in defining their scope and purpose
      (average score 80%, range 56%-100%). Guidelines recommended either or both the
      tuberculin skin test and the interferon gamma release assay for screening.
      Treatment of LTBI with isoniazid was consistently recommended. CONCLUSION:
      Clinical practice guidelines on LTBI vary in quality and scope. The
      recommendations for screening varied across guidelines, while recommendations for
      treatment were largely consistent. Improving the consistency and quality of
      guidelines may help to optimise the screening and management of LTBI for improved
      patient outcomes.

PMID- 30209158
TI  - Improving access to healthcare for women in Tanzania by addressing socioeconomic
      determinants and health insurance: a population-based cross-sectional survey.
AB  - OBJECTIVE: This study was performed to explore the factors associated with
      accumulation of multiple problems in accessing healthcare among women in Tanzania
      as an example of a low-income country. DESIGN: Population-based cross-sectional
      survey. SETTING: Nationwide representative data for women of reproductive age
      obtained from the 2015-2016 Tanzania Demographic and Health Survey were analysed.
      PRIMARY OUTCOME MEASURES: A composite variable, 'problems in accessing
      healthcare', with five (1-5) categories was created based on the number of
      problems reported: obtaining permission to go to the doctor, obtaining money to
      pay for advice or treatment, distance to a health facility and not wanting to go
      alone. Respondents who reported fewer or more problems placed in lower and higher
      categories, respectively. RESULTS: A total of 13 266 women aged 15-49 years, with
      a median age (IQR) of 27 (20-36) years were interviewed and included in the
      analysis. About two-thirds (65.53%) of the respondents reported at least one of
      the four major problems in accessing healthcare. Furthermore, after controlling
      for other variables included in the final model, women without any type of health
      insurance, those belonging to the poorest class according to the wealth index,
      those who had not attended any type of formal education, those who were not
      employed for cash, each year of increasing age and those who were divorced,
      separated or widowed were associated with greater problems in accessing
      healthcare. CONCLUSION: This study indicated the additive effects of barriers to
      healthcare in low-income countries such as Tanzania. Based on these results,
      improving uptake of health insurance and addressing social determinants of health
      are the first steps towards reducing women's problems associated with accessing
      healthcare.

PMID- 30209160
TI  - AACR Cancer Progress Report 2018: Harnessing Research Discoveries for Patient
      Benefit.

PMID- 30209159
TI  - Explaining variations in test ordering in primary care: protocol for a realist
      review.
AB  - INTRODUCTION: Studies have demonstrated the existence of significant variation in
      test-ordering patterns in both primary and secondary care, for a wide variety of
      tests and across many health systems. Inconsistent practice could be explained by
      differing degrees of underuse and overuse of tests for diagnosis or monitoring.
      Underuse of appropriate tests may result in delayed or missed diagnoses; overuse
      may be an early step that can trigger a cascade of unnecessary intervention, as
      well as being a source of harm in itself. METHODS AND ANALYSIS: This realist
      review will seek to improve our understanding of how and why variation in
      laboratory test ordering comes about. A realist review is a theory-driven
      systematic review informed by a realist philosophy of science, seeking to produce
      useful theory that explains observed outcomes, in terms of relationships between
      important contexts and generative mechanisms.An initial explanatory theory will
      be developed in consultation with a stakeholder group and this 'programme theory'
      will be tested and refined against available secondary evidence, gathered via an
      iterative and purposive search process. This data will be analysed and
      synthesised according to realist principles, to produce a refined 'programme
      theory', explaining the contexts in which primary care doctors fail to order
      'necessary' tests and/or order 'unnecessary' tests, and the mechanisms underlying
      these decisions. ETHICS AND DISSEMINATION: Ethical approval is not required for
      this review. A complete and transparent report will be produced in line with the
      RAMESES standards. The theory developed will be used to inform recommendations
      for the development of interventions designed to minimise 'inappropriate'
      testing. Our dissemination strategy will be informed by our stakeholders. A
      variety of outputs will be tailored to ensure relevance to policy-makers, primary
      care and pathology practitioners, and patients. PROSPERO REGISTRATION NUMBER:
      CRD42018091986.

PMID- 30209162
TI  - Heartbeat: Social isolation is associated with increased mortality after acute
      myocardial infarction or stroke.

PMID- 30209163
TI  - Conclusions are inappropriate due to the big discrepancies between groups.

PMID- 30209164
TI  - Challenging decompensated aortic valve stenosis.

PMID- 30209161
TI  - TP53 outperforms other androgen receptor biomarkers to predict abiraterone or
      enzalutamide outcome in metastatic castration-resistant prostate cancer.
AB  - PURPOSE: To infer the prognostic value of simultaneous androgen receptor (AR) and
      TP53 profiling in liquid biopsies from metastatic castration-resistant prostate
      cancer (mCRPC) patients starting a new line of AR signalling inhibitors (ARSi).
      EXPERIMENTAL DESIGN: Between March 2014 and April 2017, we recruited mCRPC
      patients (n=168) prior to ARSi in a cohort study encompassing 10 European
      centres. Blood samples were collected for comprehensive profiling of CellSearch
      enriched circulating tumour cells (CTCs) and circulating tumour DNA (ctDNA).
      Targeted CTC RNA-seq allowed the detection of eight AR splice variants (ARVs).
      Low-pass whole-genome and targeted gene-body sequencing of AR and TP53 was
      applied to identify amplifications, loss-of-heterozygosity, mutations and
      structural rearrangements in ctDNA. Clinical or radiological progression-free
      survival (PFS) was estimated by Kaplan-Meier analysis, and independent
      associations were determined using multivariable Cox-regression models. RESULTS:
      Overall, no single AR perturbation remained associated with adverse prognosis
      after multivariable analysis. Instead, tumour burden estimates (CTC counts, ctDNA
      fraction, and visceral metastases) were significantly associated with PFS. TP53
      inactivation harbored independent prognostic value (HR 1.88, 95%CI 1.18-3.00, p =
      0.008), and outperformed ARV expression and detection of genomic AR alterations.
      Using Cox coefficient analysis of clinical parameters and TP53 status, we
      identified three prognostic groups with differing PFS estimates (median, 14.7 vs
      7.51 vs 2.62 months, p < 0.0001), which was validated in an independent mCRPC
      cohort (n=202) starting first-line ARSi (median, 14.3 vs 6.39 vs 2.23 months, p <
      0.0001). CONCLUSIONS: In an all-comer cohort, tumour burden estimates and TP53
      outperform any AR perturbation to infer prognosis.

PMID- 30209165
TI  - Modulation of Vaccine-Induced CD4 T Cell Functional Profiles by Changes in
      Components of HIV Vaccine Regimens in Humans.
AB  - To date, six vaccine strategies have been evaluated in clinical trials for their
      efficacy at inducing protective immune responses against HIV infection. However,
      only the ALVAC-HIV/AIDSVAX B/E vaccine (RV144 trial) has demonstrated protection,
      albeit modestly (31%; P = 0.03). One potential correlate of protection was a low
      frequency HIV-specific CD4 T cell population with diverse functionality. Although
      CD4 T cells, particularly T follicular helper (Tfh) cells, are critical for
      effective antibody responses, most studies involving HIV vaccines have focused on
      humoral immunity or CD8 T cell effector responses, and little is known about the
      functionality and frequency of vaccine-induced CD4 T cells. We therefore assessed
      responses from several phase I/II clinical trials and compared them to responses
      to natural HIV-1 infection. We found that all vaccines induced a lower magnitude
      of HIV-specific CD4 T cell responses than that observed for chronic infection.
      Responses differed in functionality, with a CD40 ligand (CD40L)-dominated
      response and more Tfh cells after vaccination, whereas chronic HIV infection
      provoked tumor necrosis factor alpha (TNF-alpha)-dominated responses. The vaccine
      delivery route further impacted CD4 T cells, showing a stronger Th1 polarization
      after dendritic cell delivery than after intramuscular vaccination. In
      prime/boost regimens, the choice of prime and boost influenced the functional
      profile of CD4 T cells to induce more or less polyfunctionality. In summary,
      vaccine-induced CD4 T cell responses differ remarkably between vaccination
      strategies, modes of delivery, and boosts and do not resemble those induced by
      chronic HIV infection. Understanding the functional profiles of CD4 T cells that
      best facilitate protective antibody responses will be critical if CD4 T cell
      responses are to be considered a clinical trial go/no-go criterion.IMPORTANCE
      Only one HIV-1 candidate vaccine strategy has shown protection, albeit marginally
      (31%), against HIV-1 acquisition, and correlates of protection suggested that a
      multifunctional CD4 T cell immune response may be important for this protective
      effect. Therefore, the functional phenotypes of HIV-specific CD4 T cell responses
      induced by different phase I and phase II clinical trials were assessed to better
      show how different vaccine strategies influence the phenotype and function of HIV
      specific CD4 T cell immune responses. The significance of this research lies in
      our comprehensive comparison of the compositions of the T cell immune responses
      to different HIV vaccine modalities. Specifically, our work allows for the
      evaluation of vaccination strategies in terms of their success at inducing Tfh
      cell populations.

PMID- 30209166
TI  - Global Analysis of Baculovirus Autographa californica Multiple
      Nucleopolyhedrovirus Gene Expression in the Midgut of the Lepidopteran Host
      Trichoplusia ni.
AB  - The baculovirus Autographa californica multiple nucleopolyhedrovirus (AcMNPV) is
      a large double-stranded DNA (dsDNA) virus that encodes approximately 156 genes
      and is highly pathogenic to a variety of larval lepidopteran insects in nature.
      Oral infection of larval midgut cells is initiated by the occlusion-derived virus
      (ODV), while secondary infection of other tissues is mediated by the budded virus
      (BV). Global viral gene expression has been studied in detail in BV-infected cell
      cultures, but studies of ODV infection in the larval midgut are limited. In this
      study, we examined expression of the ~156 AcMNPV genes in Trichoplusia ni midgut
      tissue using a transcriptomic approach. We analyzed expression profiles of viral
      genes in the midgut and compared them with profiles from a T. ni cell line
      (Tnms42). Several viral genes (p6.9, orf76, orf75, pp31, Ac-bro, odv-e25, and odv
      ec27) had high expression levels in the midgut throughout the infection. Also,
      the expression of genes associated with occlusion bodies (polh and p10) appeared
      to be delayed in the midgut in comparison with the cell line. Comparisons of
      viral gene expression profiles revealed remarkable similarities between the
      midgut and cell line for most genes, although substantial differences were
      observed for some viral genes. These included genes associated with high level BV
      production (fp-25k), acceleration of systemic infection (v-fgf), and enhancement
      of viral movement (arif-1/orf20). These differential expression patterns appear
      to represent specific adaptations for virus infection and transmission through
      the polarized cells of the lepidopteran midgut.IMPORTANCE Baculoviruses such as
      AcMNPV are pathogens that are natural regulators of certain insect populations.
      Baculovirus infections are biphasic, with a primary phase initiated by oral
      infection of midgut epithelial cells by occlusion-derived virus (ODV) virions and
      a secondary phase in which other tissues are infected by budded-virus (BV)
      virions. While AcMNPV infections in cultured cells have been studied extensively,
      comparatively little is known regarding primary infection in the midgut. In these
      studies, we identified gene expression patterns associated with ODV-mediated
      infection of the midgut in Trichoplusia ni and compared those results with prior
      results from BV-infected cultured cells, which simulate secondary infection.
      These studies provide a detailed analysis of viral gene expression patterns in
      the midgut, which likely represent specific viral strategies to (i) overcome or
      avoid host defenses in the gut and (ii) rapidly move infection from the midgut,
      into the hemocoel to facilitate systemic infection.

PMID- 30209167
TI  - The Human Cytomegalovirus US27 Gene Product Constitutively Activates Antioxidant
      Response Element-Mediated Transcription through Gbetagamma, Phosphoinositide 3
      Kinase, and Nuclear Respiratory Factor 1.
AB  - Human cytomegalovirus (HCMV) is a widespread pathogen that modulates host
      chemokine signaling during persistent infection in the host. HCMV encodes four
      proteins with homology to the chemokine receptor family of G protein-coupled
      receptors (GPCRs): US27, US28, UL33, and UL78. Each of the four receptors
      modulates host CXCR4 signaling. US28, UL33, and UL78 impair CXCR4 signaling
      outcomes, while US27 enhances signaling, as evidenced by increased calcium
      mobilization and cell migration to CXCL12. To investigate the effects of US27 on
      CXCR4 during virus infection, fibroblasts were infected with bacterial artificial
      chromosome-derived clinical strain HCMV TB40/E-mCherry (wild type [WT]), mutants
      lacking US27 (TB40/E-mCherry-US27Delta [US27Delta]) or all four GPCRs (TB40 E
      mCherry-allDelta), or mutants expressing only US27 but not US28, UL33, or UL78
      (TB40/E-mCherry-US27wt [US27wt]). CXCR4 gene expression was significantly higher
      in WT- and US27wt-infected fibroblasts. This effect was evident at 3 h
      postinfection, suggesting that US27 derived from the parental virion enhanced
      CXCR4 expression. Reporter gene assays demonstrated that US27 increased
      transcriptional activity regulated by the antioxidant response element (ARE), and
      small interfering RNA treatment indicated that this effect was mediated by NRF-1,
      the primary transcription factor for CXCR4. Increased translocation of NRF-1 into
      the nucleus of WT-infected cells compared to mock- or US27Delta-infected cells
      was confirmed by immunofluorescence microscopy. Chemical inhibitors targeting
      Gbetagamma and phosphoinositide 3-kinase (PI3K) ablated the increase in ARE
      driven transcription, implicating these proteins as mediators of US27-stimulated
      gene transcription. This work identifies the first signaling pathway activated by
      HCMV US27 and may reveal a novel regulatory function for this orphan viral
      receptor in stimulating stress response genes during infection.IMPORTANCE Human
      cytomegalovirus (HCMV) is the most common congenital infection worldwide, causing
      deafness, blindness, and other serious birth defects. CXCR4 is a human chemokine
      receptor that is crucial for both fetal development and immune responses. We
      found that the HCMV protein US27 stimulates increased expression of CXCR4 through
      activation of the transcription factor nuclear respiratory factor 1 (NRF-1). NRF
      1 regulates stress response genes that contain the antioxidant response element
      (ARE), and HCMV infection is associated with increased expression of many stress
      response genes when US27 is present. Our results show that the US27 protein
      activates the NRF-1/ARE pathway, stimulating higher expression of CXCR4 and other
      stress response genes, which is likely to be beneficial for virus replication
      and/or immune evasion.

PMID- 30209168
TI  - Interplay between the Poly(A) Tail, Poly(A)-Binding Protein, and Coronavirus
      Nucleocapsid Protein Regulates Gene Expression of Coronavirus and the Host Cell.
AB  - In the present study, we investigated the roles of interactions among the poly(A)
      tail, coronavirus nucleocapsid (N) protein, and poly(A)-binding protein (PABP) in
      the regulation of coronavirus gene expression. Through dissociation constant (Kd
      ) comparison, we found that the coronavirus N protein can bind to the poly(A)
      tail with high affinity, establishing N protein as a PABP. A subsequent analysis
      with UV cross-linking and immunoprecipitation revealed that the N protein is able
      to bind to the poly(A) tail in infected cells. Further examination demonstrated
      that poly(A) tail binding by the N protein negatively regulates translation of
      coronaviral RNA and host mRNA both in vitro and in cells. Although the N protein
      can interact with PABP and eukaryotic initiation factor 4G (eIF4G), the poor
      interaction efficiency between the poly(A)-bound N protein and eIF4E may explain
      the observed decreased translation efficiency. In addition to interaction with
      translation factor eIF4G, the N protein is able to interact with coronavirus
      nonstructural protein 9 (nsp9), a replicase protein required for replication. The
      study demonstrates interactions among the poly(A) tail, N protein, and PABP both
      in vitro and in infected cells. Of the interactions, binding of the poly(A) tail
      to N protein decreases the interaction efficiency between the poly(A) tail and
      eIF4E, leading to translation inhibition. The poly(A)-dependent translation
      inhibition by N protein has not been previously demonstrated and thus extends our
      understanding of coronavirus gene expression.IMPORTANCE Gene expression in
      coronavirus is a complicated and dynamic process. In this study, we demonstrated
      that coronavirus N protein is able to bind to the poly(A) tail with high
      affinity, establishing N protein as a PABP. We also show how the interplay
      between coronavirus 3' poly(A) tail, PABP, and N protein regulates gene
      expression of the coronavirus and host cell. Of the interactions, poly(A) tail
      binding by the N protein negatively regulates translation, and to our knowledge,
      this inhibition of translation by binding of the N protein to poly(A) tail has
      not been previously studied. Accordingly, the study provides fundamental
      molecular details regarding coronavirus infection and expands our knowledge of
      coronavirus gene expression.

PMID- 30209169
TI  - Reovirus Neurotropism and Virulence Are Dictated by Sequences in the Head Domain
      of the Viral Attachment Protein.
AB  - Viral capsid components that bind cellular receptors mediate critical functions
      in viral tropism and disease pathogenesis. Mammalian orthoreoviruses (reoviruses)
      spread systemically in newborn mice to cause serotype-specific disease in the
      central nervous system (CNS). Serotype 1 (T1) reovirus infects ependymal cells to
      cause nonlethal hydrocephalus, whereas serotype 3 (T3) reovirus infects neurons
      to cause fulminant and lethal encephalitis. This serotype-dependent difference in
      tropism and concomitant disease is attributed to the sigma1 viral attachment
      protein, which is composed of head, body, and tail domains. To identify sigma1
      sequences that contribute to tropism for specific cell types in the CNS, we
      engineered a panel of viruses expressing chimeric sigma1 proteins in which
      discrete sigma1 domains have been reciprocally exchanged. Parental and chimeric
      sigma1 viruses were compared for replication, tropism, and disease induction
      following intracranial inoculation of newborn mice. Viruses expressing T1 sigma1
      head sequences infect the ependyma, produce relatively lower titers in the brain,
      and do not cause significant disease. In contrast, viruses expressing T3 sigma1
      head sequences efficiently infect neurons, replicate to relatively higher titers
      in the brain, and cause a lethal encephalitis. Additionally, T3 sigma1 head
      expressing viruses display enhanced infectivity of cultured primary cortical
      neurons compared with T1 sigma1 head-expressing viruses. These results indicate
      that T3 sigma1 head domain sequences promote infection of neurons, likely by
      interaction with a neuron-specific receptor, and dictate tropism in the CNS and
      induction of encephalitis.IMPORTANCE Viral encephalitis is a serious and often
      life-threatening inflammation of the brain. Mammalian orthoreoviruses are
      promising oncolytic therapeutics for humans but establish virulent, serotype
      dependent disease in the central nervous system (CNS) of many young mammals.
      Serotype 1 reoviruses infect ependymal cells and produce hydrocephalus, whereas
      serotype 3 reoviruses infect neurons and cause encephalitis. Reovirus
      neurotropism is hypothesized to be dictated by the filamentous sigma1 viral
      attachment protein. However, it is not apparent how this protein mediates
      disease. We discovered that sequences forming the most virion-distal domain of T1
      and T3 sigma1 coordinate infection of either ependyma or neurons, respectively,
      leading to mutually exclusive patterns of tropism and disease in the CNS. These
      studies contribute new knowledge about how reoviruses target cells for infection
      in the brain and inform the rational design of improved oncolytic therapies to
      mitigate difficult-to-treat tumors of the CNS.

PMID- 30209170
TI  - Epstein-Barr Virus MicroRNA miR-BART5-3p Inhibits p53 Expression.
AB  - Epstein-Barr virus (EBV) is the first human virus found to encode many microRNAs.
      It is etiologically linked to nasopharyngeal carcinoma and EBV-associated gastric
      carcinoma. During the latent infection period, there are only a few EBV proteins
      expressed, whereas EBV microRNAs, such as the BamHI-A region rightward transcript
      (BART) microRNAs, are highly expressed. However, how these BART miRNAs precisely
      regulate the tumor growth in nasopharyngeal carcinoma and gastric carcinoma
      remains obscure. Here, we report that upregulation of EBV-miR-BART5-3p promotes
      the growth of nasopharyngeal carcinoma and gastric carcinoma cells. BART5-3p
      directly targets the tumor suppressor gene TP53 on its 3'-untranslated region (3'
      UTR) and consequently downregulates CDKN1A, BAX, and FAS expression, leading to
      acceleration of the cell cycle progress and inhibition of cell apoptosis. BART5
      3p contributes to the resistance to chemotherapeutic drugs and ionizing
      irradiation-induced p53 increase. Moreover, BART5-3p also facilitates degradation
      of p53 proteins. BART5-3p is the first EBV-microRNA to be identified as
      inhibiting p53 expression and function, which suggests a novel mechanism
      underlying the strategies employed by EBV to maintain latent infection and
      promote the development of EBV-associated carcinomas.IMPORTANCE EBV encodes 44
      mature microRNAs, which have been proven to promote EBV-associated diseases by
      targeting host genes and self-viral genes. In EBV-associated carcinomas, the
      expression of viral protein is limited but the expression of BART microRNAs is
      extremely high, suggesting that they could be major factors in the contribution
      of EBV-associated tumorigenesis. p53 is a critical tumor suppressor. Unlike in
      most human solid tumors, TP53 mutations are rare in nasopharyngeal carcinoma and
      EBV-associated gastric carcinoma tissues, suggesting a possibility that some EBV
      encoded products suppress the functions of p53. This study provides the first
      evidence that a BART microRNA can suppress p53 expression by directly targeting
      its 3'-UTR. This study implies that EBV can use its BART microRNAs to modulate
      the expression of p53, thus maintaining its latency and contributing to
      tumorigenesis.

PMID- 30209171
TI  - A Single Point Mutation in the Rhinovirus 2B Protein Reduces the Requirement for
      Phosphatidylinositol 4-Kinase Class III Beta in Viral Replication.
AB  - Rhinoviruses (RVs) replicate on cytoplasmic membranes derived from the Golgi
      apparatus. They encode membrane-targeted proteins 2B, 2C, and 3A, which control
      trafficking and lipid composition of the replication membrane. The virus recruits
      host factors for replication, such as phosphatidylinositol 4 (PI4)-kinase 3beta
      (PI4K3b), which boosts PI4-phosphate (PI4P) levels and drives lipid
      countercurrent exchange of PI4P against cholesterol at endoplasmic reticulum
      Golgi membrane contact sites through the lipid shuttling protein oxysterol
      binding protein 1 (OSBP1). We identified a PI4K3b inhibitor-resistant RV-A16
      variant with a single point mutation in the conserved 2B protein near the
      cytosolic carboxy terminus, isoleucine 92 to threonine (termed 2B[I92T]). The
      mutation did not confer resistance to cholesterol-sequestering compounds or OSBP1
      inhibition, suggesting invariant dependency on the PI4P/cholesterol lipid
      countercurrents. In the presence of PI4K3b inhibitor, Golgi reorganization and
      PI4P lipid induction occurred in RV-A16 2B[I92] but not in wild-type infection.
      The knockout of PI4K3b abolished the replication of both the 2B[I92T] mutant and
      the wild type. Doxycycline-inducible expression of PI4K3b in PI4K3b knockout
      cells efficiently rescued the 2B[I92T] mutant and, less effectively, wild-type
      virus infection. Ectopic expression of 2B[I92T] or 2B was less efficient than
      that of 3A in recruiting PI4K3b to perinuclear membranes, suggesting a supportive
      rather than decisive role of 2B in recruiting PI4K3b. The data suggest that 2B
      tunes the recruitment of PI4K3b to the replication membrane and allows the virus
      to adapt to cells with low levels of PI4K3b while still maintaining the
      PI4P/cholesterol countercurrent for establishing Golgi-derived RV replication
      membranes.IMPORTANCE Human rhinoviruses (RVs) are the major cause of the common
      cold worldwide. They cause asthmatic exacerbations and chronic obstructive
      pulmonary disease. Despite recent advances, the development of antivirals and
      vaccines has proven difficult due to the high number and variability of RV types.
      The identification of critical host factors and their interactions with viral
      proteins and membrane lipids for the establishment of viral replication is a
      basis for drug development strategies. Our findings here shed new light on the
      interactions between nonstructural viral membrane proteins and class III
      phosphatidylinositol 4 kinases from the host and highlight the importance of
      phosphatidylinositol 4 phosphate for RV replication.

PMID- 30209172
TI  - The nucleolar protein LYAR facilitates ribonucleoprotein assembly of influenza A
      virus.
AB  - Influenza A viral ribonucleoprotein (vRNP) is responsible for transcription and
      replication of the viral genome in infected cells and depend on host factors for
      its functions. Identification of the host factors interacting with vRNP not only
      improves understanding of virus-host interactions, but also provides insights
      into novel mechanisms of viral pathogenicity and the development of new antiviral
      strategies. Here, we have identified eighty host factors that co-purified with
      vRNP using affinity purification followed by mass spectrometry. LYAR, a cell
      growth-regulating nucleolar protein, has been shown to be important for influenza
      A virus replication. During influenza A virus infection, LYAR expression is
      increased and it partly translocates from the nucleolus to nucleoplasm and
      cytoplasm. Furthermore, LYAR interacts with RNP subunits, resulting in enhancing
      viral RNP assembly, thereby facilitating viral RNA synthesis. Taken together, our
      studies identify a novel vRNP binding host partner important for influenza A
      virus replication, and further reveal the mechanism of LYAR regulating influenza
      A viral RNA synthesis by facilitating viral RNP assembly.IMPORTANCE Influenza A
      virus (IAV) must utilize the host cell machinery to replicate, but many of the
      mechanisms of the IAV-host interaction remain poorly understood. Improved
      understanding of interactions between host factors and vRNP not only increases
      our basic knowledge of the molecular mechanisms of virus replication and
      pathogenicity, but also provides insights into possible novel antiviral targets
      that are necessary due to the widespread emergence of drug-resistant IAV strains.
      Herein, we have identified LYAR, a cell growth-regulating nucleolar protein,
      which interacts with viral RNP components and is important for efficient
      replication of IAVs, and whose role in the IAV life cycle has never been
      reported. In addition, we further reveal the role of LYAR in viral RNA synthesis.
      Our results extend and improve the current knowledge on the mechanisms of IAV
      transcription and replication.

PMID- 30209173
TI  - Susceptibility to Neutralization by Broadly Neutralizing Antibodies Generally
      Correlates with Infected Cell Binding for a Panel of Clade B HIV Reactivated from
      Latent Reservoirs.
AB  - Efforts to cure human immunodeficiency virus (HIV) infection are obstructed by
      reservoirs of latently infected CD4+ T cells that can reestablish viremia. HIV
      specific broadly neutralizing antibodies (bNAbs), defined by unusually wide
      neutralization breadths against globally diverse viruses, may contribute to the
      elimination of these reservoirs by binding to reactivated cells, thus targeting
      them for immune clearance. However, the relationship between neutralization of
      reservoir isolates and binding to corresponding infected primary CD4+ T cells has
      not been determined. Thus, the extent to which neutralization breadths and
      potencies can be used to infer the corresponding parameters of infected cell
      binding is currently unknown. We assessed the breadths and potencies of bNAbs
      against 36 viruses reactivated from peripheral blood CD4+ T cells from
      antiretroviral (ARV)-treated HIV-infected individuals by using paired
      neutralization and infected cell binding assays. Single-antibody breadths ranged
      from 0 to 64% for neutralization (80% inhibitory concentration [IC80] of <=10
      MUg/ml) and from 0 to 89% for binding, with two-antibody combinations (results
      for antibody combinations are theoretical/predicted) reaching levels of 0 to 83%
      and 50 to 100%, respectively. Infected cell binding correlated with virus
      neutralization for 10 of 14 antibodies (e.g., for 3BNC117, r = 0.82 and P <
      0.0001). Heterogeneity was observed, however, with a lack of significant
      correlation for 2G12, CAP256.VRC26.25, 2F5, and 4E10. Our results provide
      guidance on the selection of bNAbs for interventional cure studies, both by
      providing a direct assessment of intra- and interindividual variabilities in
      neutralization and infected cell binding in a novel cohort and by defining the
      relationships between these parameters for a panel of bNAbs.IMPORTANCE Although
      antiretroviral therapies have improved the lives of people who are living with
      HIV, they do not cure infection. Efforts are being directed towards harnessing
      the immune system to eliminate the virus that persists, potentially resulting in
      virus-free remission without medication. HIV-specific antibodies hold promise for
      such therapies owing to their ability to both prevent the infection of new cells
      (neutralization) and direct the killing of infected cells. We isolated 36 HIV
      strains from individuals whose virus was suppressed by medication and tested 14
      different antibodies for neutralization of these viruses and for binding to cells
      infected with the same viruses (critical for engaging natural killer cells). For
      both neutralization and infected cell binding, we observed variation both between
      individuals and amongst different viruses within an individual. For most
      antibodies, neutralization activity correlated with infected cell binding. These
      data provide guidance on the selection of antibodies for clinical trials.

PMID- 30209174
TI  - Human Host Range Restriction of the Vaccinia Virus C7/K1 Double Deletion Mutant
      Is Mediated by an Atypical Mode of Translation Inhibition.
AB  - Replication of vaccinia virus in human cells depends on the viral C7 or K1
      protein. A previous human genome-wide short interfering RNA (siRNA) screen with a
      C7/K1 double deletion mutant revealed SAMD9 as a principal host range restriction
      factor along with additional candidates, including WDR6 and FTSJ1. To compare
      their abilities to restrict replication, the cellular genes were individually
      inactivated by CRISPR/Cas9 mutagenesis. The C7/K1 deletion mutant exhibited
      enhanced replication in each knockout (KO) cell line but reached wild-type levels
      only in SAMD9 KO cells. SAMD9 was not depleted in either WDR6 or FTSJ1 KO cells,
      suggesting less efficient alternative rescue mechanisms. Using the SAMD9 KO cells
      as controls, we verified a specific block in host and viral intermediate and late
      protein synthesis in HeLa cells and demonstrated that the inhibition could be
      triggered by events preceding viral DNA replication. Inhibition of cap-dependent
      and -independent protein synthesis occurred primarily at the translational level,
      as supported by DNA and mRNA transfection experiments. Concurrent with collapse
      of polyribosomes, viral mRNA was predominantly in 80S and lighter
      ribonucleoprotein fractions. We confirmed the accumulation of cytoplasmic
      granules in HeLa cells infected with the C7/K1 deletion mutant and further showed
      that viral mRNA was sequestered with SAMD9. RNA granules were still detected in
      G3BP KO U2OS cells, which remained nonpermissive for the C7/K1 deletion mutant.
      Inhibition of cap-dependent and internal ribosome entry site-mediated
      translation, sequestration of viral mRNA, and failure of PKR, RNase L, or G3BP KO
      cells to restore protein synthesis support an unusual mechanism of host
      restriction.IMPORTANCE A dynamic relationship exists between viruses and their
      hosts in which each ostensibly attempts to exploit the other's vulnerabilities. A
      window is opened into the established condition, which evolved over millennia, if
      loss-of-function mutations occur in either the virus or host. Thus, the inability
      of viral host range mutants to replicate in specific cells can be overcome by
      identifying and inactivating the opposing cellular gene. Here, we investigated a
      C7/K1 host range mutant of vaccinia virus in which the cellular gene SAMD9 serves
      as the principal host restriction factor. Host restriction was triggered early in
      infection and manifested as a block in translation of viral mRNAs. Features of
      the block include inhibition of cap-dependent and internal ribosome entry site
      mediated translation, sequestration of viral RNA, and inability to overcome the
      inhibition by inactivation of protein kinase R, ribonuclease L, or G3 binding
      proteins, suggesting a novel mechanism of host restriction.

PMID- 30209175
TI  - Distribution, Diversity, and Evolution of Endogenous Retroviruses in
      Perissodactyl Genomes.
AB  - The evolution of mammalian genomes has been shaped by interactions with
      endogenous retroviruses (ERVs). In this study, we investigated the distribution
      and diversity of ERVs in the mammalian order Perissodactyla, with a view to
      understanding their impact on the evolution of modern equids (family Equidae). We
      characterize the major ERV lineages in the horse genome in terms of their genomic
      distribution, ancestral genome organization, and time of activity. Our results
      show that subsequent to their ancestral divergence from rhinoceroses and tapirs,
      equids acquired four novel ERV lineages. We show that two of these ERV lineages
      proliferated extensively in the lineage leading to modern horses, and one
      contains loci that are actively transcribed in specific tissues. In addition, we
      show that the white rhinoceros has resisted germ line colonization by
      retroviruses for more than 54 million years-longer than any other extant
      mammalian species. The map of equine ERVs that we provide here will be of great
      utility to future studies aiming to investigate the potential functional roles of
      equine ERVs and their impact on equine evolution.IMPORTANCE ERVs in the host
      genome are highly informative about the long-term interactions of retroviruses
      and hosts. They are also interesting because they have influenced the evolution
      of mammalian genomes in various ways. In this study, we derive a calibrated
      timeline describing the process through which ERV diversity has been generated in
      the equine germ line. We determined the distribution and diversity of
      perissodactyl ERV lineages and inferred their retrotranspositional activity
      during evolution, thereby gaining insight into the long-term coevolutionary
      history of retroviruses and mammals. Our study provides a platform for future
      investigations to identify equine ERV loci involved in physiological processes
      and/or pathological conditions.

PMID- 30209176
TI  - HOIL1 Is Essential for the Induction of Type I and III Interferons by MDA5 and
      Regulates Persistent Murine Norovirus Infection.
AB  - The linear ubiquitin chain assembly complex (LUBAC), composed of heme-oxidized
      IRP2 ubiquitin ligase 1 (HOIL1), HOIL1-interacting protein (HOIP), and SHANK
      associated RH domain-interacting protein (SHARPIN), is a crucial regulator of
      multiple immune signaling pathways. In humans, HOIL1 or HOIP deficiency is
      associated with an immune disorder involving autoinflammation, immunodeficiency,
      and inflammatory bowel disease (IBD)-like symptoms. During viral infection, LUBAC
      is reported to inhibit the induction of interferon (IFN) by the cytosolic RNA
      sensor retinoic acid-inducible gene I (RIG-I). Surprisingly, we found that HOIL1
      is essential for the induction of both type I and type III IFNs, as well as the
      phosphorylation of IFN regulatory factor 3 (IRF3), during murine norovirus (MNoV)
      infection in cultured dendritic cells. The RIG-I-like receptor, melanoma
      differentiation-associated protein 5 (MDA5), is also required for IFN induction
      and IRF3 phosphorylation during MNoV infection. Furthermore, HOIL1 and MDA5 were
      required for IFN induction after Theiler's murine encephalomyelitis virus
      infection and poly(I.C) transfection, but not Sendai virus or vesicular
      stomatitis virus infection, indicating that HOIL1 and LUBAC are required
      selectively for MDA5 signaling. Moreover, Hoil1 - / - mice exhibited defective
      control of acute and persistent murine norovirus infection and defective
      regulation of MNoV persistence by the microbiome as also observed previously for
      mice deficient in interferon lambda (IFN-lambda) receptor, signal transducer and
      activator of transcription factor 1 (STAT1), and IRF3. These data indicate that
      LUBAC plays a critical role in IFN induction to control RNA viruses sensed by
      MDA5.IMPORTANCE Human noroviruses are a leading cause of gastroenteritis
      throughout the world but are challenging to study in vivo and in vitro Murine
      norovirus (MNoV) provides a tractable genetic and small-animal model to study
      norovirus biology and immune responses. Interferons are critical mediators of
      antiviral immunity, but excessive expression can dysregulate the immune system.
      IFN-lambda plays an important role at mucosal surfaces, including the
      gastrointestinal tract, and both IFN-lambda and commensal enteric bacteria are
      important modulators of persistent MNoV infection. LUBAC, of which HOIL1 is a
      component, is reported to inhibit type I IFN induction after RIG-I stimulation.
      We show, in contrast, that HOIL1 is critical for type I and III IFN induction
      during infection with MNoV, a virus that preferentially activates MDA5. Moreover,
      HOIL1 regulates MNoV infection in vivo These data reveal distinct functions for
      LUBAC in these closely related signaling pathways and in modulation of IFN
      expression.

PMID- 30209177
TI  - Recombinant Infectious Bronchitis Viruses Expressing Chimeric Spike Glycoproteins
      Induce Partial Protective Immunity against Homologous Challenge despite Limited
      Replication In Vivo.
AB  - Vaccination regimes against Infectious bronchitis virus (IBV), which are based on
      a single virus serotype, often induce insufficient levels of cross-protection
      against serotypes and two or more antigenically diverse vaccines are used in
      attempt to provide broader protection. Amino acid differences in the surface
      protein, spike (S), in particular the S1 subunit, are associated with poor cross
      protection. Here, homologous vaccination trials with recombinant IBVs (rIBVs),
      based on the apathogenic strain, BeauR, were conducted to elucidate the role of
      S1 in protection. A single vaccination of specific-pathogen-free chickens with
      rIBV expressing S1 of virulent strains M41 or QX, BeauR-M41(S1) and BeauR-QX(S1),
      gave incomplete protection against homologous challenge, based on ciliary
      activity and clinical signs. There could be conformational issues with the spike
      if heterologous S1 and S2 are linked, suggesting a homologous S2 might be
      essential. To address this, a homologous vaccination-challenge trial
      incorporating rIBVs expressing full spike from M41, BeauR-M41(S), and S2 subunit
      from M41, BeauR-M41(S2) was conducted. All chimeric viruses grew to similar
      titers in vitro, induced virus-specific partial protective immunity, evident by
      cellular infiltrations, reductions in viral RNA load in the trachea and
      conjunctiva and higher serum anti-IBV titers. Collectively, these findings show
      that vaccination with rIBVs primed the birds for challenge but the viruses were
      cleared rapidly from the mucosal tissues in the head. Chimeric S1 and S2 viruses
      did not protect as effectively as BeauR-M41(S) based on ciliary activity and
      clinical signs. Booster vaccinations and an rIBV with improved in vivo
      replication may improve the levels of protection.IMPORTANCE Infectious bronchitis
      virus causes an acute, highly contagious respiratory disease, responsible for
      significant economic losses to the poultry industry. Amino acid differences in
      the surface protein, spike (S), in particular the S1 subunit, have been
      associated with poor cross-protection. Available vaccines give poor cross
      protection and rationally designed live attenuated vaccines, based on apathogenic
      BeauR, could address these. Here, to determine the role of S1 in protection, a
      series of homologous vaccination trials with rIBVs were conducted. Single
      vaccinations with chimeric rIBVs induced virus-specific partial protective
      immunity, characterized by reduction in viral load and serum antibody titers.
      However, BeauR-M41(S) was the only vaccination to improve the level of protection
      against clinical signs and the loss of tracheal ciliary activity. Growth
      characteristics show that all of the rIBVs replicated in vitro to similar levels.
      Booster vaccinations and an rIBV with improved in vivo replication may improve
      the levels of protection.

PMID- 30209180
TI  - Learning curves in surgery: variables, analysis and applications.
AB  - Learning curves graphically represent the relationship between learning effort
      and learning outcome. Learning curves are increasingly used in research, the
      design of randomised controlled trials, the assessment of competency, healthcare
      education and training programme design. In this review we have outlined the
      principles behind plotting learning curves, described the common methods used to
      analyse learning curves, how to interpret learning curves, the multitude of
      learning models, their applications and potential pitfalls, and the importance of
      a mathematically rigorous approach to learning curve analytics.

PMID- 30209179
TI  - Hepatitis B Spliced Protein (HBSP) Suppresses Fas-Mediated Hepatocyte Apoptosis
      via Activation of PI3K/Akt Signaling.
AB  - Hepatitis B spliced protein (HBSP) is known to associate with viral persistence
      and pathogenesis; however, its biological and clinical significance remains
      poorly defined. Acquired resistance to Fas-mediated apoptosis is thought to be
      one of the major promotors for hepatitis B virus (HBV) chronicity and malignancy.
      The purpose of this study was to investigate whether HBSP could protect
      hepatocytes against Fas-initiated apoptosis. We showed here that HBSP mediated
      resistance of hepatoma cells or primary human hepatocytes (PHH) to agonistic anti
      Fas antibody (CH11)- or FasL-induced apoptosis. Under Fas signaling stimulation,
      expression of HBSP inhibited Fas aggregation and prevented recruitment of the
      adaptor molecule Fas-associated death domain (FADD) and procaspase-8 (or FADD
      like interleukin-1beta-converting enzyme [FLICE]) into the death-inducing
      signaling complex (DISC) while increasing recruitment of cellular FLICE
      inhibitory protein L (FLIPL) into the DISC. Those effects may be mediated through
      activation of the phosphoinositide 3-kinase (PI3K)/Akt pathway as evidenced by
      increased cellular phosphatidylinositol (3,4,5)-trisphosphate (PIP3) content and
      PI3K activity and enhanced phosphorylation of mTORC2 and PDPK1 as well as Akt
      itself. Confirmedly, inhibition of PI3K by LY294002 reversed the effect of HBSP
      on Fas aggregation, FLIPL expression, and cellular apoptosis. These results
      indicate that HBSP functions to prevent hepatocytes from Fas-induced apoptosis by
      enhancing PI3K/Akt activity, which may contribute to the survival and persistence
      of infected hepatocytes during chronic infection.IMPORTANCE Our study revealed a
      previously unappreciated role of HBSP in Fas-mediated apoptosis. The
      antiapoptotic activity of HBSP is important for understanding hepatitis B virus
      pathogenesis. In particular, HBV variants associated with hepatoma carcinoma may
      downregulate apoptosis of hepatocytes through enhanced HBSP expression. Our study
      also found that Akt is centrally involved in Fas-induced hepatocyte apoptosis and
      revealed that interventions directed at inhibiting the activation or functional
      activity of Akt may be of therapeutic value in this process.

PMID- 30209178
TI  - Type I Interferon Signaling Prevents Hepatitis B Virus-Specific T Cell Responses
      by Reducing Antigen Expression.
AB  - Robust virus-specific CD8+ T cell responses are required for the clearance of
      hepatitis B virus (HBV). However, the factors that determine the magnitude of HBV
      specific CD8+ T cell responses are poorly understood. To examine the impact of
      genetic variations of HBV on HBV-specific CD8+ T cell responses, we introduced
      three HBV clones (Aa_IND [Aa], C_JPN22 [C22], and D_IND60 [D60]) that express
      various amounts of HBV antigens into the livers of C57BL/6 (B6) (H-2b) mice and
      B10.D2 (H-2d) mice. In B6 mice, clone C22 barely induced HBV-specific CD8+ T cell
      responses and persisted the longest, while clone D60 elicited strong HBV-specific
      CD8+ T cell responses and was rapidly cleared. These differences between HBV
      clones largely diminished in H-2d mice. Interestingly, the magnitude of HBV
      specific CD8+ T cell responses in B6 mice was associated with the HB core antigen
      expression level during the early phase of HBV transduction. Surprisingly, robust
      HBV-specific CD8+ T cell responses to clone C22 were induced in interferon
      alpha/beta receptor-deficient (IFN-alphabetaR-/-) (H-2b) mice. The induction of
      HBV-specific CD8+ T cell responses to C22 in IFN-alphabetaR-/- mice reflects
      enhanced HBV antigen expression because the suppression of antigen expression by
      HBV-specific small interfering RNA (siRNA) attenuated HBV-specific T cell
      responses in IFN-alphabetaR-/- mice and prolonged HBV expression. Collectively,
      these results suggest that HBV genetic variation and type I interferon signaling
      determine the magnitude of HBV-specific CD8+ T cell responses by regulating the
      initial antigen expression levels.IMPORTANCE Hepatitis B virus (HBV) causes acute
      and chronic infection, and approximately 240 million people are chronically
      infected with HBV worldwide. It is generally believed that virus-specific CD8+ T
      cell responses are required for the clearance of HBV. However, the relative
      contributions of genetic variation and innate immune responses to the induction
      of HBV-specific CD8+ T cell responses are not fully understood. In this study, we
      discovered that different clearance rates between HBV clones after hydrodynamic
      transduction were associated with the magnitude of HBV-specific CD8+ T cell
      responses and initial HB core antigen expression. Surprisingly, type I interferon
      signaling negatively regulated HBV-specific CD8+ T cell responses by reducing
      early HBV antigen expression. These results show that the magnitude of the HBV
      specific CD8+ T cell response is regulated primarily by the initial antigen
      expression level.

PMID- 30209182
TI  - Proficiency of WHO Global Foodborne Infections Network External Quality Assurance
      System Participants in Identification and Susceptibility Testing of
      Thermotolerant Campylobacter spp. from 2003 to 2012.
AB  - Campylobacter spp. are foodborne and waterborne pathogens. While rather accurate
      estimates for these pathogens are available in industrialized countries, a lack
      of diagnostic capacity in developing countries limits accurate assessments of
      prevalence in many regions. Proficiency in the identification and susceptibility
      testing of these organisms is critical for surveillance and control efforts. The
      aim of the study was to assess performance for identification and susceptibility
      testing of thermotolerant Campylobacter spp. among laboratories participating in
      the World Health Organization (WHO) Global Foodborne Infections Network (GFN)
      External Quality Assurance System (EQAS) over a 9-year period. Participants
      (primarily national-level laboratories) were encouraged to self-evaluate their
      performance as part of continuous quality improvement. The ability to correctly
      identify Campylobacter spp. varied by year and ranged from 61.9% (2008) to 90.7%
      (2012), and the ability to correctly perform antimicrobial susceptibility testing
      (AST) for Campylobacter spp. appeared to steadily increase from 91.4% to 93.6% in
      the test period (2009 to 2012). The poorest performance (60.0% correct
      identification and 86.8% correct AST results) was observed in African
      laboratories. Overall, approximately 10% of laboratories reported either an
      incorrect identification or antibiogram. As most participants were supranational
      reference laboratories, these data raise significant concerns regarding capacity
      and proficiency at the local clinical level. Addressing these diagnostic
      challenges is critical for both patient-level management and broader surveillance
      and control efforts.

PMID- 30209183
TI  - Identifying Mixed Mycobacterium tuberculosis Infection and Laboratory Cross
      Contamination during Mycobacterial Sequencing Programs.
AB  - The detection of laboratory cross-contamination and mixed tuberculosis infections
      is an important goal of clinical mycobacteriology laboratories. The objective of
      this study was to develop a method to detect mixtures of different Mycobacterium
      tuberculosis lineages in laboratories performing mycobacterial next-generation
      sequencing (NGS). The setting was the Public Health England National
      Mycobacteriology Laboratory Birmingham, which performs Illumina sequencing on DNA
      extracted from positive mycobacterial growth indicator tubes. We analyzed 4,156
      samples yielding M. tuberculosis from 663 MiSeq runs, which were obtained during
      development and production use of a diagnostic process using NGS. The counts of
      the most common (major) variant and all other variants (nonmajor variants) were
      determined from reads mapping to positions defining M. tuberculosis lineages.
      Expected variation was estimated during process development. For each sample, we
      determined the nonmajor variant proportions at 55 sets of lineage-defining
      positions. The nonmajor variant proportion in the two most mixed lineage-defining
      sets (F2 metric) was compared with that of the 47 least-mixed lineage-defining
      sets (F47 metric). The following three patterns were observed: (i) not mixed by
      either metric; (ii) high F47 metric, suggesting mixtures of multiple lineages;
      and (iii) samples compatible with mixtures of two lineages, detected by
      differential F2 metric elevations relative to F47. Pattern ii was observed in
      batches, with similar patterns in the M. tuberculosis H37Rv control present in
      each run, and is likely to reflect cross-contamination. During production, the
      proportions of samples in the patterns were 97%, 2.8%, and 0.001%, respectively.
      The F2 and F47 metrics described could be used for laboratory process control in
      laboratories sequencing M. tuberculosis genomes.

PMID- 30209181
TI  - The Psychopharmacology of Effort-Related Decision Making: Dopamine, Adenosine,
      and Insights into the Neurochemistry of Motivation.
AB  - Effort-based decision making is studied using tasks that offer choices between
      high-effort options leading to more highly valued reinforcers versus low
      effort/low-reward options. These tasks have been used to study the involvement of
      neural systems, including mesolimbic dopamine and related circuits, in effort
      related aspects of motivation. Moreover, such tasks are useful as animal models
      of some of the motivational symptoms that are seen in people with depression,
      schizophrenia, Parkinson's disease, and other disorders. The present review will
      discuss the pharmacology of effort-related decision making and will focus on the
      use of these tasks for the development of drug treatments for motivational
      dysfunction. Research has identified pharmacological conditions that can alter
      effort-based choice and serve as models for depression-related symptoms (e.g.,
      the vesicular monoamine transport-2 inhibitor tetrabenazine and proinflammatory
      cytokines). Furthermore, tests of effort-based choice have identified compounds
      that are particularly useful for stimulating high-effort work output and
      reversing the deficits induced by tetrabenazine and cytokines. These studies
      indicate that drugs that act by facilitating dopamine transmission, as well as
      adenosine A2A antagonists, are relatively effective at reversing effort-related
      impairments. Studies of effort-based choice may lead to the identification of
      drug targets that could be useful for treating motivational treatments that are
      resistant to commonly used antidepressants such as serotonin transport
      inhibitors.

PMID- 30209184
TI  - Clinical and Analytical Evaluation of the Anyplex II HPV HR Detection Assay
      within the VALGENT-3 Framework.
AB  - In 2012, VALidation of human papillomavirus (HPV) GENotyping Tests (VALGENT) was
      initiated to provide a formalized and uniform study framework for comparison and
      validation of HPV assays with genotyping capability. In VALGENT-3, the clinical
      and analytical performance of Anyplex II HPV HR detection (Anyplex) was compared
      to that of the Hybrid Capture 2 HPV DNA test (hc2) and the cobas 4800 HPV test
      (cobas). The panel comprises 1,300 stored samples that were obtained from women
      25 to 64 years old who participated in the Slovenian cancer screening program,
      enriched with 300 samples from women with abnormal cervical cytology. The
      sensitivity and specificity of Anyplex were noninferior to those of hc2, with a
      relative sensitivity of 1.01 (95% confidence interval [CI], 0.97 to 1.04) for
      cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and 1.01 (95% CI,
      0.97 to 1.06) for CIN3+ and relative specificity of 1.02 (95% CI, 1.00 to 1.03)
      for a CIN grade of <=1. The clinical sensitivity of Anyplex for CIN2+ and CIN3+
      was comparable to that of hc2 (P values for McNemar test [p McN] of 0.655 and
      0.564, respectively), but its specificity was significantly higher (p McN =
      0.008). The sensitivity and specificity of Anyplex were also noninferior to those
      of cobas, with relative sensitivity of 1.01 (95% CI, 0.98 to 1.04) for CIN2+ and
      1.01 (95% CI, 0.99 to 1.04) for CIN3+ and relative specificity of 1.00 (95% CI,
      0.99 to 1.01) (p McN value of >0.05 in all cases). Regardless of the clinical
      outcome (CIN2+ or CIN3+), age restriction (women >=30 years old), or comparator
      test used, Anyplex consistently showed excellent clinical performance and can be
      considered validated for primary cervical cancer screening.

PMID- 30209185
TI  - Sonication versus Tissue Sampling for Diagnosis of Prosthetic Joint and Other
      Orthopedic Device-Related Infections.
AB  - Current guidelines recommend collection of multiple tissue samples for diagnosis
      of prosthetic joint infections (PJI). Sonication of explanted devices has been
      proposed as a potentially simpler alternative; however, reported microbiological
      yield varies. We evaluated sonication for diagnosis of PJI and other orthopedic
      device-related infections (DRI) at the Oxford Bone Infection Unit between October
      2012 and August 2016. We compared the performance of paired tissue and sonication
      cultures against a "gold standard" of published clinical and composite clinical
      and microbiological definitions of infection. We analyzed explanted devices and a
      median of five tissue specimens from 505 procedures. Among clinically infected
      cases the sensitivity of tissue and sonication culture was 69% (95% confidence
      interval, 63 to 75) and 57% (50 to 63), respectively (P < 0.0001). Tissue culture
      was more sensitive than sonication for both PJI and other DRI, irrespective of
      the infection definition used. Tissue culture yield was higher for all subgroups
      except less virulent infections, among which tissue and sonication culture yield
      were similar. The combined sensitivity of tissue and sonication culture was 76%
      (70 to 81) and increased with the number of tissue specimens obtained. Tissue
      culture specificity was 97% (94 to 99), compared with 94% (90 to 97) for
      sonication (P = 0.052) and 93% (89 to 96) for the two methods combined. Tissue
      culture is more sensitive and may be more specific than sonication for diagnosis
      of orthopedic DRI in our setting. Variable methodology and case mix may explain
      reported differences between centers in the relative yield of tissue and
      sonication culture. Culture yield was highest for both methods combined.

PMID- 30209186
TI  - Diagnostic Accuracy of BD Phoenix CPO Detect for Carbapenemase Production in 190
      Enterobacteriaceae Isolates.
AB  - The rapid and accurate detection of carbapenemase-producing Enterobacteriaceae
      (CPE) is necessary for patient management and infection control measures. We
      compared the performance of the BD Phoenix CPO Detect with that of a homemade
      Carba NP assay and a modified carbapenem inactivation method (mCIM) by
      challenging all 3 assays with 190 isolates of Enterobacteriaceae with meropenem
      MICs of >0.125 mg/liter. A total of 160 isolates produced KPC-, IMI-1-, NDM-, IMP
      , and OXA-type carbapenemases, while 30 isolates were negative for carbapenemase
      production. The sensitivity and specificity were 90.6% (95% confidence interval
      [CI], 85.0% to 94.7%) and 100.0% (95% CI, 88.4% to 100.0%), respectively, for the
      Carba NP; 100.0% (95% CI, 97.7% to 100.0%) and 96.7% (95% CI, 82.7% to 99.9%),
      respectively, for the mCIM; and 89.4% (95% CI, 83.5% to 93.7%) and 66.7% (95% CI,
      47.2% to 82.7%), respectively, for the BD Phoenix CPO Detect. In particular, the
      BD CPO Detect failed to detect a significant number of CPE with IMI-1. While the
      BD Phoenix CPO Detect is able to classify carbapenemases and is built into
      routine susceptibility testing with the potential to reduce the time to CPE
      detection, its low specificity means that a positive result will need
      confirmatory testing by another method.

PMID- 30209187
TI  - Baculovirus-Induced Fast-Acting Innate Immunity Kills Liver-Stage Plasmodium.
AB  - Baculovirus (BV), an enveloped insect virus with a circular dsDNA genome,
      possesses unique characteristics that induce strong innate immune responses in
      mammalian cells. In this study, we show that BV administration in BALB/c mice not
      only provides complete protection against a subsequent Plasmodium berghei
      sporozoite infection for up to 7 d after the injection but also eliminates
      existing liver-stage parasites completely. The elimination of sporozoites by BV
      was superior to that by primaquine, and this effect occurred in a TLR9
      independent manner. At 6 h after BV administration, IFN-alpha and IFN-gamma were
      robustly produced in the serum, and RNA transcripts of IFN-stimulated genes were
      markedly upregulated in the liver compared with control mice. The in vivo passive
      transfer of serum after BV administration effectively eliminated liver-stage
      parasites, and IFN-alpha neutralization abolished this effect, indicating that
      the BV liver-stage parasite-killing mechanism is downstream of the type I IFN
      signaling pathway. These findings provide evidence that BV-induced, fast-acting
      innate immunity completely kills liver-stage parasites and, thus, may lead to new
      malaria drug and vaccine strategies.

PMID- 30209188
TI  - Bmi1 Regulates IkappaBalpha Degradation via Association with the SCF Complex.
AB  - Bmi1 is a polycomb group protein and regulator that stabilizes the ubiquitination
      complex PRC1 in the nucleus with no evidently direct link to the NF-kappaB
      pathway. In this study, we report a novel function of Bmi1: its regulation of
      IkappaBalpha ubiquitination in the cytoplasm. A deficiency of Bmi1 inhibited NF
      kappaB-mediated gene expression in vitro and a NF-kappaB-mediated mouse model of
      arthritis in vivo. Mechanistic analysis showed that Bmi1 associated with the SCF
      ubiquitination complex via its N terminus and with phosphorylation by an
      IKKalpha/beta-dependent pathway, leading to the ubiquitination of IkappaBalpha.
      These effects on NF-kappaB-related inflammation suggest Bmi1 in the SCF complex
      is a potential therapeutic target for various diseases and disorders, including
      autoimmune diseases.

PMID- 30209190
TI  - Cutting Edge: TGF-beta and Phosphatidylinositol 3-Kinase Signals Modulate
      Distinct Metabolism of Regulatory T Cell Subsets.
AB  - Murine Foxp3+ regulatory T cells (Tregs) differentiated in vitro (induced Tregs
      [iTregs]) in the presence of anti-inflammatory cytokine TGF-beta rely
      predominantly upon lipid oxidation to fuel mitochondrial oxidative
      phosphorylation. Foxp3 expression underlies this metabolic preference, as it
      suppresses glycolysis and drives oxidative phosphorylation. In this study, we
      show that in contrast to iTregs, thymic-derived Tregs (tTregs), engage in
      glycolysis and glutaminolysis at levels comparable to effector T cells despite
      maintained Foxp3 expression. Interestingly, exposure of tTregs to the anti
      inflammatory cytokine TGF-beta represses PI3K-mediated mTOR signaling, inhibits
      glucose transporter and Hk2 expression, and reprograms their metabolism to favor
      oxidative phosphorylation. Conversely, replicating the effects of inflammation
      via elevation of PI3K signaling has minimal effects on tTregs but dramatically
      enhances the glycolysis of normally oxidative iTregs, resulting in reduction of
      Foxp3 expression. Collectively, these findings suggest both extrinsic and
      intrinsic factors govern the unique metabolic signature of Treg subsets.

PMID- 30209191
TI  - Cutting Edge: The Heat Shock Protein gp96 Activates Inflammasome-Signaling
      Platforms in APCs.
AB  - Several heat shock proteins (HSPs) prime immune responses, which are, in part, a
      result of activation of APCs. APCs respond to these immunogenic HSPs by
      upregulating costimulatory molecules and secreting cytokines, including IL-1beta.
      These HSP-mediated responses are central mediators in pathological conditions
      ranging from cancer, sterile inflammation associated with trauma, and rheumatoid
      arthritis. We tested in this study the requirement of inflammasomes in the
      release of IL-1beta by one immunogenic HSP, gp96. Our results show that murine
      APCs activate NLRP3 inflammasomes in response to gp96 by K+ efflux. This is shown
      to initiate inflammatory conditions in vivo in the absence of additional known
      inflammasome activators or infection. These results document a novel mechanism by
      which proteins of endogenous origin, the HSPs, can modulate an inflammatory
      response following their release from aberrant cells.

PMID- 30209189
TI  - Influenza A Virus Infection Causes Chronic Lung Disease Linked to Sites of Active
      Viral RNA Remnants.
AB  - Clinical and experimental observations suggest that chronic lung disease is
      linked to respiratory viral infection. However, the long-term aspect of this
      relationship is not yet defined using a virus that replicates at properly high
      levels in humans and a corresponding animal model. In this study, we show that
      influenza A virus infection achieves 1 * 106-fold increases in viral load in the
      lung and dose-dependent severity of acute illness in mice. Moreover, these events
      are followed by persistence of negative- and positive-strand viral RNA remnants
      for 15 wk and chronic lung disease for at least 26 wk postinfection. The disease
      is manifested by focal areas of bronchiolization and mucus production that
      contain increased levels of viral RNA remnants along with mucin Muc5ac and Il13
      mRNA compared with uninvolved areas of the lung. Excess mucus production and
      associated airway hyperreactivity (but not fibrosis or emphysema) are partially
      attenuated with loss of IL-13 production or signaling (using mice with IL-13 or
      STAT6 deficiency). These deficiencies cause reciprocal increases in l17a mRNA and
      neutrophils in the lung; however, none of these disease endpoints are changed
      with IL-13/IL-17a compared with IL-13 deficiency or STAT6/IL-17a compared with
      STAT6 deficiency. The results establish the capacity of a potent human
      respiratory virus to produce chronic lung disease focally at sites of active
      viral RNA remnants, likely reflecting locations of viral replication that
      reprogram the region. Viral dose dependency of disease also implicates high-level
      viral replication and severity of acute infection as determinants of chronic lung
      diseases such as asthma and COPD with IL-13-dependent and IL-13/IL-17-independent
      mechanisms.

PMID- 30209192
TI  - Chemotherapy Combines Effectively with Anti-PD-L1 Treatment and Can Augment
      Antitumor Responses.
AB  - Immunotherapy with checkpoint inhibitors has proved to be highly effective, with
      durable responses in a subset of patients. Given their encouraging clinical
      activity, checkpoint inhibitors are increasingly being tested in clinical trials
      in combination with chemotherapy. In many instances, there is little
      understanding of how chemotherapy might influence the quality of the immune
      response generated by checkpoint inhibitors. In this study, we evaluated the
      impact of chemotherapy alone or in combination with anti-PD-L1 in a responsive
      syngeneic tumor model. Although multiple classes of chemotherapy treatment
      reduced immune cell numbers and activity in peripheral tissues, chemotherapy did
      not antagonize but in many cases augmented the antitumor activity mediated by
      anti-PD-L1. This dichotomy between the detrimental effects in peripheral tissues
      and enhanced antitumor activity was largely explained by the reduced dependence
      on incoming cells for antitumor efficacy in already established tumors. The
      effects of the various chemotherapies were also agent specific, and synergy with
      anti-PD-L1 was achieved by different mechanisms that ultimately helped establish
      a new threshold for response. These results rationalize the combination of
      chemotherapy with immunotherapy and suggest that, despite the negative systemic
      effects of chemotherapy, effective combinations can be obtained through distinct
      mechanisms acting within the tumor.

PMID- 30209193
TI  - Cardiotrophin-like Cytokine Increases Macrophage-Foam Cell Transition.
AB  - CLCF1 is a neurotrophic and B cell-stimulating factor belonging to the IL-6
      family. Mutations in the gene coding for CLCF1 or its secretion partner CRLF1
      lead to the development of severe phenotypes, suggesting important nonredundant
      roles in development, metabolism, and immunity. Although CLCF1 was shown to
      promote the proliferation of the myeloid cell line M1, its roles on myeloid
      activation remain underinvestigated. We characterized the effects of CLCF1 on
      myeloid cells with a focus on monocyte-macrophage and macrophage-foam cell
      differentiations. CLCF1 injections in mice resulted in a significant increase in
      CD11b+ circulating cells, including proinflammatory monocytes. Furthermore, CLCF1
      activated STAT3 phosphorylation in bone marrow CD11b+ cells and in bone marrow
      derived macrophages (BMDM). BMDM stimulated with CLCF1 produced a large array of
      proinflammatory factors comprising IL-6, IL-9, G-CSF, GM-CSF, IL-1beta, IL-12,
      CCL5, and CX3CL1. The pattern of cytokines and chemokines released by CLCF1
      treated BMDM led us to investigate the role of CLCF1 in foam cell formation. When
      pretreated with CLCF1, BMDM presented a marked SR-A1 upregulation, an increase in
      acetylated-low-density lipoprotein uptake, and an elevated triglyceride
      accumulation. CLCF1-induced SR-A1 upregulation, triglyceride accumulation, and
      acetylated-low-density lipoprotein uptake could be prevented using ruxolitinib, a
      JAK inhibitor, indicating that the effects of the cytokine on myeloid cells
      result from activation of the canonical JAK/STAT signaling pathway. Our data
      reveal novel biological roles for CLCF1 in the control of myeloid function and
      identify this cytokine as a strong inducer of macrophage-foam cell transition,
      thus bringing forward a new potential therapeutic target for atherosclerosis.

PMID- 30209195
TI  - Inhaled corticosteroid containing combinations and mortality in COPD.

PMID- 30209197
TI  - Systemic oxidative stress in congenital central hypoventilation syndrome.

PMID- 30209196
TI  - Haemodynamics and serial risk assessment in systemic sclerosis associated
      pulmonary arterial hypertension.
AB  - The prognostic importance of follow-up haemodynamics and the validity of
      multidimensional risk assessment are not well established for systemic sclerosis
      (SSc)-associated pulmonary arterial hypertension (PAH).We assessed incident SSc
      PAH patients to determine the association between clinical and haemodynamic
      variables at baseline and first follow-up right heart catheterisation (RHC) with
      transplant-free survival. RHC variables included cardiac index, stroke volume
      index (SVI), pulmonary arterial compliance and pulmonary vascular resistance.
      Risk assessment was performed according to the number of low-risk criteria:
      functional class I or II, 6-min walking distance (6MWD) >440 m, right atrial
      pressure <8 mmHg and cardiac index >=2.5 L.min-1.m-2Transplant-free survival from
      diagnosis (n=513) was 87%, 55% and 35% at 1, 3 and 5 years, respectively. At
      baseline, 6MWD was the only independent predictor. A follow-up RHC was available
      for 353 patients (median interval 4.6 months, interquartile range 3.9-6.4
      months). The 6MWD, functional class, cardiac index, SVI, pulmonary arterial
      compliance and pulmonary vascular resistance were independently associated with
      transplant-free survival at follow-up, with SVI performing better than other
      haemodynamic variables. 1-year outcomes were better with increasing number of low
      risk criteria at baseline (area under the curve (AUC) 0.63, 95% CI 0.56-0.69) and
      at first follow-up (AUC 0.71, 95% CI 0.64-0.78).Follow-up haemodynamics and
      multidimensional risk assessment had greater prognostic significance than at
      baseline in SSc-PAH.

PMID- 30209198
TI  - Whole genome sequencing of Mycobacterium tuberculosis.

PMID- 30209194
TI  - Does early onset asthma increase childhood obesity risk? A pooled analysis of 16
      European cohorts.
AB  - The parallel epidemics of childhood asthma and obesity over the past few decades
      have spurred research into obesity as a risk factor for asthma. However, little
      is known regarding the role of asthma in obesity incidence. We examined whether
      early-onset asthma and related phenotypes are associated with the risk of
      developing obesity in childhood.This study includes 21 130 children born from
      1990 to 2008 in Denmark, France, Germany, Greece, Italy, The Netherlands, Spain,
      Sweden and the UK. We followed non-obese children at 3-4 years of age for
      incident obesity up to 8 years of age. Physician-diagnosed asthma, wheezing and
      allergic rhinitis were assessed up to 3-4 years of age.Children with physician
      diagnosed asthma had a higher risk for incident obesity than those without asthma
      (adjusted hazard ratio (aHR) 1.66, 95% CI 1.18-2.33). Children with active asthma
      (wheeze in the last 12 months and physician-diagnosed asthma) exhibited a higher
      risk for obesity (aHR 1.98, 95% CI 1.31-3.00) than those without wheeze and
      asthma. Persistent wheezing was associated with increased risk for incident
      obesity compared to never wheezers (aHR 1.51, 95% CI 1.08-2.09).Early-onset
      asthma and wheezing may contribute to an increased risk of developing obesity in
      later childhood.

PMID- 30209199
TI  - The Mechanical Ventilation-Respiratory Distress Observation Scale as a surrogate
      of self-reported dyspnoea in intubated patients.

PMID- 30209200
TI  - European Union standard for tuberculosis care on treatment of multidrug-resistant
      tuberculosis following new World Health Organization recommendations.

PMID- 30209201
TI  - Peer Review Week 2018: Diversity in Peer Review.

PMID- 30209202
TI  - Neural Mechanisms Underlying Schemas and Inferences.

PMID- 30209203
TI  - Cereblon Regulates BK Channel Expression at Presynaptic and Postsynaptic Sites in
      Excitatory Synapses.

PMID- 30209205
TI  - Drosophila Exo70 Is Essential for Neurite Extension and Survival under Thermal
      Stress.
AB  - The octomeric exocyst complex governs the final step of exocytosis in both plants
      and animals. Its roles, however, extend beyond exocytosis and include organelle
      biogenesis, ciliogenesis, cell migration, and cell growth. Exo70 is a conserved
      component of the exocyst whose function in Drosophila is unclear. In this study,
      we characterized two mutant alleles of Drosophila exo70. exo70 mutants exhibit
      reduced synaptic growth, locomotor activity, glutamate receptor density, and
      mEPSP amplitude. We found that presynaptic Exo70 is necessary for normal synaptic
      growth at the neuromuscular junction (NMJ). At the neuromuscular junction, exo70
      genetically interacts with the small GTPase ralA to regulate synaptic growth.
      Loss of Exo70 leads to the blockage of JNK signaling-, activity-, and temperature
      induced synaptic outgrowths. We showed that this phenotype is associated with an
      impairment of integral membrane protein transport to the cell surface at synaptic
      terminals. In octopaminergic motor neurons, Exo70 is detected in synaptic
      varicosities, as well as the regions of membrane extensions in response to
      activity stimulation. Strikingly, mild thermal stress causes severe neurite
      outgrowth defects and pharate adult lethality in exo70 mutants. exo70 mutants
      also display defective locomotor activity in response to starvation stress. These
      results demonstrated that Exo70 is an important regulator of induced synaptic
      growth and is crucial for an organism's adaptation to environmental
      changes.SIGNIFICANCE STATEMENT The exocyst complex is a conserved protein complex
      directing secretory vesicles to the site of membrane fusion during exocytosis,
      which is essential for transporting proteins and membranes to the cell surface.
      Exo70 is a subunit of the exocyst complex whose roles in neurons remain elusive,
      and its function in Drosophila is unclear. In Drosophila, Exo70 is expressed in
      both glutamatergic and octopaminergic neurons, and presynaptic Exo70 regulates
      synaptic outgrowth. Moreover, exo70 mutants have impaired integral membrane
      transport to the cell surface at synaptic terminals and block several kinds of
      induced synaptic growth. Remarkably, elevated temperature causes severe
      arborization defects and lethality in exo70 mutants, thus underpinning the
      importance of Exo70 functions in development and adaptation to the environment.

PMID- 30209206
TI  - CRISPR-Cas immunity, DNA repair and genome stability.
AB  - Co-opting of CRISPR-Cas 'Interference' reactions for editing the genomes of
      eukaryotic and prokaryotic cells has highlighted crucial support roles for DNA
      repair systems that strive to maintain genome stability. As front-runners in
      genome editing that targets DNA, the class 2 CRISPR-Cas enzymes Cas9 and Cas12a
      rely on repair of DNA double-strand breaks (DDSBs) by host DNA repair enzymes,
      using mechanisms that vary in how well they are understood. Data are emerging
      about the identities of DNA repair enzymes that support genome editing in human
      cells. At the same time, it is becoming apparent that CRISPR-Cas systems
      functioning in their native environment, bacteria or archaea, also need DNA
      repair enzymes. In this short review, we survey how DNA repair and CRISPR-Cas
      systems are intertwined. We consider how understanding DNA repair and CRISPR-Cas
      interference reactions in nature might help improve the efficacy of genome
      editing procedures that utilise homologous or analogous systems in human and
      other cells.

PMID- 30209207
TI  - Heated tobacco products: another tobacco industry global strategy to slow
      progress in tobacco control.
AB  - There has been a global decline in tobacco consumption that, if continued, will
      negatively impact the tobacco industry's profits. This decline led the industry
      to invent and market new products, including heated tobacco products (HTP). HTP
      are an extension of the industry's strategies to undermine government's tobacco
      regulatory efforts as they are being promoted as part of the solution for the
      tobacco epidemic. Under the moniker of 'harm reduction', the tobacco companies
      are attempting to rehabilitate their reputation so they can more effectively
      influence governments to roll back existing tobacco control policies or create
      exemptions for their HTP. Rolling back tobacco control policies will make it
      easier for the companies to renormalise tobacco use to increase social
      acceptability for all their products. When regulations are absent or when
      loopholes exist in classifying HTP as a tobacco product (thus subject to all
      tobacco control regulations), the industry's marketing of HTP is making these
      products more visible to the public and more accessible. Governments need to
      ensure that HTP are regulated as tobacco products or drugs and reject
      partnerships with the tobacco companies to promote 'harm reduction'. The tobacco
      companies remain the vector of the tobacco-caused epidemic and cannot be part of
      the global tobacco control solution.

PMID- 30209204
TI  - Memory-Related Synaptic Plasticity Is Sexually Dimorphic in Rodent Hippocampus.
AB  - Men are generally superior to women in remembering spatial relationships, whereas
      the reverse holds for semantic information, but the neurobiological bases for
      these differences are not understood. Here we describe striking sexual dimorphism
      in synaptic mechanisms of memory encoding in hippocampal field CA1, a region
      critical for spatial learning. Studies of acute hippocampal slices from adult
      rats and mice show that for excitatory Schaffer-commissural projections, the
      memory-related long-term potentiation (LTP) effect depends upon endogenous
      estrogen and membrane estrogen receptor alpha (ERalpha) in females but not in
      males; there was no evident involvement of nuclear ERalpha in females, or of
      ERbeta or GPER1 (G-protein-coupled estrogen receptor 1) in either sex.
      Quantitative immunofluorescence showed that stimulation-induced activation of two
      LTP-related kinases (Src, ERK1/2), and of postsynaptic TrkB, required ERalpha in
      females only, and that postsynaptic ERalpha levels are higher in females than in
      males. Several downstream signaling events involved in LTP were comparable
      between the sexes. In contrast to endogenous estrogen effects, infused estradiol
      facilitated LTP and synaptic signaling in females via both ERalpha and ERbeta.
      The estrogen dependence of LTP in females was associated with a higher threshold
      for both inducing potentiation and acquiring spatial information. These results
      indicate that the observed sexual dimorphism in hippocampal LTP reflects
      differences in synaptic kinase activation, including both a weaker association
      with NMDA receptors and a greater ERalpha-mediated kinase activation in response
      to locally produced estrogen in females. We propose that male/female differences
      in mechanisms and threshold for field CA1 LTP contribute to differences in
      encoding specific types of memories.SIGNIFICANCE STATEMENT There is good evidence
      for male/female differences in memory-related cognitive function, but the
      neurobiological basis for this sexual dimorphism is not understood. Here we
      describe sex differences in synaptic function in a brain area that is critical
      for learning spatial cues. Our results show that female rodents have higher
      synaptic levels of estrogen receptor alpha (ERalpha) and, in contrast to males,
      require membrane ERalpha for the activation of signaling kinases that support
      long-term potentiation (LTP), a form of synaptic plasticity thought to underlie
      learning. The additional requirement of estrogen signaling in females resulted in
      a higher threshold for both LTP and hippocampal field CA1-dependent spatial
      learning. These results describe a synaptic basis for sexual dimorphism in
      encoding spatial information.

PMID- 30209208
TI  - Light and mild redux: heated tobacco products' reduced exposure claims are likely
      to be misunderstood as reduced risk claims.
AB  - INTRODUCTION: Heated tobacco products (HTPs) are being marketed in several
      countries around the world with claims that they are less harmful than combusted
      cigarettes, based on assertions that they expose users to lower levels of
      toxicants. In the USA, Philip Morris International (PMI) has submitted an
      application to the Food and Drug Administration (FDA) in 2016 seeking
      authorisation to market its HTPs, IQOS, with reduced risk and reduced exposure
      claims. METHODS: We examined the PMI's Perception and Behavior Assessment Studies
      evaluating perceptions of reduced risk claims that were submitted to the FDA and
      made publicly available. RESULTS: Qualitative and quantitative studies conducted
      by PMI demonstrate that adult consumers in the USA perceive reduced exposure
      claims as reduced risk claims. CONCLUSION: The data in the PMI modified risk
      tobacco product IQOS application do not support reduced risk claims and the
      reduced exposure claims are perceived as reduced risk claims, which is explicitly
      prohibited by the FDA. Allowing PMI to promote IQOS as reduced exposure would
      amount to a legally sanctioned repeat of the 'light' and 'mild' fraud which, for
      conventional cigarettes, is prohibited by the US law and the WHO Framework
      Convention on Tobacco Control.

PMID- 30209210
TI  - Response to: 'The epidemiology of malignant mesothelioma in women: gender
      differences and modalities of asbestos exposure' by Marinaccio et al.

PMID- 30209209
TI  - Letter concerning: 'Response to: 'The epidemiology of malignant mesothelioma in
      women: gender differences and modalities of asbestos exposure' by Marinaccio et
      al'.

PMID- 30209211
TI  - Cell-to-cell bacterial interactions promoted by drier conditions on soil
      surfaces.
AB  - Bacterial cell-to-cell interactions are in the core of evolutionary and
      ecological processes in soil and other environments. Under most conditions,
      natural soils are unsaturated where the fragmented aqueous habitats and thin
      liquid films confine bacterial cells within small volumes and close proximity for
      prolonged periods. We report effects of a range of hydration conditions on
      bacterial cell-level interactions that are marked by plasmid transfer between
      donor and recipient cells within populations of the soil bacterium Pseudomonas
      putida Using hydration-controlled sand microcosms, we demonstrate that the
      frequency of cell-to-cell contacts under prescribed hydration increases with
      lowering water potential values (i.e., under drier conditions where the aqueous
      phase shrinks and fragments). These observations were supported using a
      mechanistic individual-based model for linking macroscopic soil water potential
      to microscopic distribution of liquid phase and explicit bacterial cell
      interactions in a simplified porous medium. Model results are in good agreement
      with observations and inspire confidence in the underlying mechanisms. The study
      highlights important physical factors that control short-range bacterial cell
      interactions in soil and on surfaces, specifically, the central role of the
      aqueous phase in mediating bacterial interactions and conditions that promote
      genetic information transfer in support of soil microbial diversity.

PMID- 30209213
TI  - Genetic divergence and the number of hybridizing species affect the path to
      homoploid hybrid speciation.
AB  - Hybridization is often maladaptive and in some instances has led to the loss of
      biodiversity. However, hybridization can also promote speciation, such as during
      homoploid hybrid speciation, thereby generating biodiversity. Despite examples of
      homoploid hybrid species, the importance of hybridization as a speciation
      mechanism is still widely debated, and we lack a general understanding of the
      conditions most likely to generate homoploid hybrid species. Here we show that
      the level of genetic divergence between hybridizing species has a large effect on
      the probability that their hybrids evolve reproductive isolation. We find that
      populations of hybrids formed by parental species with intermediate levels of
      divergence were more likely to mate assortatively, and discriminate against their
      parental species, than those generated from weakly or strongly diverged parental
      species. Reproductive isolation was also found between hybrid populations,
      suggesting differential sorting of parental traits across populations. Finally,
      hybrid populations derived from three species were more likely to evolve
      reproductive isolation than those derived from two species, supporting arguments
      that hybridization-supplied genetic diversity can lead to the evolution of novel
      "adaptive systems" and promote speciation. Our results illustrate when we expect
      hybridization and admixture to promote hybrid speciation. Whether homoploid
      hybrid speciation is a common speciation mechanism in general remains an
      outstanding empirical question.

PMID- 30209212
TI  - Elevated A20 promotes TNF-induced and RIPK1-dependent intestinal epithelial cell
      death.
AB  - Intestinal epithelial cell (IEC) death is a common feature of inflammatory bowel
      disease (IBD) that triggers inflammation by compromising barrier integrity. In
      many patients with IBD, epithelial damage and inflammation are TNF-dependent.
      Elevated TNF production in IBD is accompanied by increased expression of the
      TNFAIP3 gene, which encodes A20, a negative feedback regulator of NF-kappaB. A20
      in intestinal epithelium from patients with IBD coincided with the presence of
      cleaved caspase-3, and A20 transgenic (Tg) mice, in which A20 is expressed from
      an IEC-specific promoter, were highly susceptible to TNF-induced IEC death,
      intestinal damage, and shock. A20-expressing intestinal organoids were also
      susceptible to TNF-induced death, demonstrating that enhanced TNF-induced
      apoptosis was a cell-autonomous property of A20. This effect was dependent on
      Receptor Interacting Protein Kinase 1 (RIPK1) activity, and A20 was found to
      associate with the Ripoptosome complex, potentiating its ability to activate
      caspase-8. A20-potentiated RIPK1-dependent apoptosis did not require the A20
      deubiquitinase (DUB) domain and zinc finger 4 (ZnF4), which mediate NF-kappaB
      inhibition in fibroblasts, but was strictly dependent on ZnF7 and A20
      dimerization. We suggest that A20 dimers bind linear ubiquitin to stabilize the
      Ripoptosome and potentiate its apoptosis-inducing activity.

PMID- 30209214
TI  - Cortical circuit activity underlying sleep slow oscillations and spindles.
AB  - Slow oscillations and sleep spindles are hallmarks of the EEG during slow-wave
      sleep (SWS). Both oscillatory events, especially when co-occurring in the
      constellation of spindles nesting in the slow oscillation upstate, are considered
      to support memory formation and underlying synaptic plasticity. The regulatory
      mechanisms of this function at the circuit level are poorly understood. Here,
      using two-photon imaging in mice, we relate EEG-recorded slow oscillations and
      spindles to calcium signals recorded from the soma of cortical putative pyramidal
      like (Pyr) cells and neighboring parvalbumin-positive interneurons (PV-Ins) or
      somatostatin-positive interneurons (SOM-Ins). Pyr calcium activity was increased
      more than threefold when spindles co-occurred with slow oscillation upstates
      compared with slow oscillations or spindles occurring in isolation. Independent
      of whether or not a spindle was nested in the slow oscillation upstate, the slow
      oscillation downstate was preceded by enhanced calcium signal in SOM-Ins that
      vanished during the upstate, whereas spindles were associated with strongly
      increased PV-In calcium activity. Additional wide-field calcium imaging of Pyr
      cells confirmed the enhanced calcium activity and its widespread topography
      associated with spindles nested in slow oscillation upstates. In conclusion, when
      spindles are nested in slow oscillation upstates, maximum Pyr activity appears to
      concur with strong perisomatic inhibition of Pyr cells via PV-Ins and low
      dendritic inhibition via SOM-Ins (i.e., conditions that might optimize synaptic
      plasticity within local cortical circuits).

PMID- 30209215
TI  - Autonomous conformational regulation of beta3 integrin and the conformation
      dependent property of HPA-1a alloantibodies.
AB  - Integrin alpha/beta heterodimer adopts a compact bent conformation in the resting
      state, and upon activation undergoes a large-scale conformational rearrangement.
      During the inside-out activation, signals impinging on the cytoplasmic tail of
      beta subunit induce the alpha/beta separation at the transmembrane and
      cytoplasmic domains, leading to the extended conformation of the ectodomain with
      the separated leg and the opening headpiece that is required for the high
      affinity ligand binding. It remains enigmatic which integrin subunit drives the
      bent-to-extended conformational rearrangement in the inside-out activation. The
      beta3 integrins, including alphaIIbbeta3 and alphaVbeta3, are the prototypes for
      understanding integrin structural regulation. The Leu33Pro polymorphism located
      at the beta3 PSI domain defines the human platelet-specific alloantigen (HPA)
      1a/b, which provokes the alloimmune response leading to clinically important
      bleeding disorders. Some, but not all, anti-HPA-1a alloantibodies can distinguish
      the alphaIIbbeta3 from alphaVbeta3 and affect their functions with unknown
      mechanisms. Here we designed a single-chain beta3 subunit that mimics a
      separation of alpha/beta heterodimer on inside-out activation. Our
      crystallographic and functional studies show that the single-chain beta3 integrin
      folds into a bent conformation in solution but spontaneously extends on the cell
      surface. This demonstrates that the beta3 subunit autonomously drives the
      membrane-dependent conformational rearrangement during integrin activation. Using
      the single-chain beta3 integrin, we identified the conformation-dependent
      property of anti-HPA-1a alloantibodies, which enables them to differently
      recognize the beta3 in the bent state vs. the extended state and in the complex
      with alphaIIb vs. alphaV This study provides deeper understandings of integrin
      conformational activation on the cell surface.

PMID- 30209216
TI  - AP2 transcription factor CBX1 with a specific function in symbiotic exchange of
      nutrients in mycorrhizal Lotus japonicus.
AB  - The arbuscular mycorrhizal (AM) symbiosis, a widespread mutualistic association
      between land plants and fungi, depends on reciprocal exchange of phosphorus
      driven by proton-coupled phosphate uptake into host plants and carbon supplied to
      AM fungi by host-dependent sugar and lipid biosynthesis. The molecular mechanisms
      and cis-regulatory modules underlying the control of phosphate uptake and de novo
      fatty acid synthesis in AM symbiosis are poorly understood. Here, we show that
      the AP2 family transcription factor CTTC MOTIF-BINDING TRANSCRIPTION FACTOR1
      (CBX1), a WRINKLED1 (WRI1) homolog, directly binds the evolutionary conserved
      CTTC motif that is enriched in mycorrhiza-regulated genes and activates Lotus
      japonicus phosphate transporter 4 (LjPT4) in vivo and in vitro. Moreover, the
      mycorrhiza-inducible gene encoding H+-ATPase (LjHA1), implicated in energizing
      nutrient uptake at the symbiotic interface across the periarbuscular membrane, is
      coregulated with LjPT4 by CBX1. Accordingly, CBX1-defective mutants show reduced
      mycorrhizal colonization. Furthermore, genome-wide-binding profiles, DNA-binding
      studies, and heterologous expression reveal additional binding of CBX1 to AW box,
      the consensus DNA-binding motif for WRI1, that is enriched in promoters of
      glycolysis and fatty acid biosynthesis genes. We show that CBX1 activates
      expression of lipid metabolic genes including glycerol-3-phosphate
      acyltransferase RAM2 implicated in acylglycerol biosynthesis. Our finding defines
      the role of CBX1 as a regulator of host genes involved in phosphate uptake and
      lipid synthesis through binding to the CTTC/AW molecular module, and supports a
      model underlying bidirectional exchange of phosphorus and carbon, a fundamental
      trait in the mutualistic AM symbiosis.

PMID- 30209217
TI  - TRIM21 mediates antibody inhibition of adenovirus-based gene delivery and
      vaccination.
AB  - Adenovirus has enormous potential as a gene-therapy vector, but preexisting
      immunity limits its widespread application. What is responsible for this immune
      block is unclear because antibodies potently inhibit transgene expression without
      impeding gene transfer into target cells. Here we show that antibody prevention
      of adenoviral gene delivery in vivo is mediated by the cytosolic antibody
      receptor TRIM21. Genetic KO of TRIM21 or a single-antibody point mutation is
      sufficient to restore transgene expression to near-naive immune levels. TRIM21 is
      also responsible for blocking cytotoxic T cell induction by vaccine vectors,
      preventing a protective response against subsequent influenza infection and an
      engrafted tumor. Furthermore, adenoviral preexisting immunity can lead to an
      augmented immune response upon i.v. administration of the vector. Transcriptomic
      analysis of vector-transduced tissue reveals that TRIM21 is responsible for the
      specific up-regulation of hundreds of immune genes, the majority of which are
      components of the intrinsic or innate response. Together, these data define a
      major mechanism underlying the preimmune block to adenovirus gene therapy and
      demonstrate that TRIM21 efficiently blocks gene delivery in vivo while
      simultaneously inducing a rapid program of immune transcription.

PMID- 30209218
TI  - Cellular hysteresis as a principle to maximize the efficacy of antibiotic
      therapy.
AB  - Antibiotic resistance has become one of the most dramatic threats to global
      health. While novel treatment options are urgently required, most attempts focus
      on finding new antibiotic substances. However, their development is costly, and
      their efficacy is often compromised within short time periods due to the enormous
      potential of microorganisms for rapid adaptation. Here, we developed a strategy
      that uses the currently available antibiotics. Our strategy exploits cellular
      hysteresis, which is the long-lasting, transgenerational change in cellular
      physiology that is induced by one antibiotic and sensitizes bacteria to another
      subsequently administered antibiotic. Using evolution experiments, mathematical
      modeling, genomics, and functional genetic analysis, we demonstrate that
      sequential treatment protocols with high levels of cellular hysteresis constrain
      the evolving bacteria by (i) increasing extinction frequencies, (ii) reducing
      adaptation rates, and (iii) limiting emergence of multidrug resistance. Cellular
      hysteresis is most effective in fast sequential protocols, in which antibiotics
      are changed within 12 h or 24 h, in contrast to the less frequent changes in
      cycling protocols commonly implemented in hospitals. We found that cellular
      hysteresis imposes specific selective pressure on the bacteria that disfavors
      resistance mutations. Instead, if bacterial populations survive, hysteresis is
      countered in two distinct ways, either through a process related to antibiotic
      tolerance or a mechanism controlled by the previously uncharacterized two
      component regulator CpxS. We conclude that cellular hysteresis can be harnessed
      to optimize antibiotic therapy, to achieve both enhanced bacterial elimination
      and reduced resistance evolution.

PMID- 30209219
TI  - Homologous recombination is an intrinsic defense against antiviral RNA
      interference.
AB  - RNA interference (RNAi) is the major antiviral defense mechanism of plants and
      invertebrates, rendering the capacity to evade it a defining factor in shaping
      the viral landscape. Here we sought to determine whether different virus
      replication strategies provided any inherent capacity to evade RNAi in the
      absence of an antagonist. Through the exploitation of host microRNAs, we
      recreated an RNAi-like environment in vertebrates and directly compared the
      capacity of positive- and negative-stranded RNA viruses to cope with this
      selective pressure. Applying this defense against four distinct viral families
      revealed that the capacity to undergo homologous recombination was the defining
      attribute that enabled evasion of this defense. Independent of gene expression
      strategy, positive-stranded RNA viruses that could undergo strand switching
      rapidly excised genomic material, while negative-stranded viruses were
      effectively targeted and cleared upon RNAi-based selection. These data suggest a
      dynamic relationship between host antiviral defenses and the biology of virus
      replication in shaping pathogen prevalence.

PMID- 30209220
TI  - LRRK2 and its substrate Rab GTPases are sequentially targeted onto stressed
      lysosomes and maintain their homeostasis.
AB  - Leucine-rich repeat kinase 2 (LRRK2) has been associated with a variety of human
      diseases, including Parkinson's disease and Crohn's disease, whereas LRRK2
      deficiency leads to accumulation of abnormal lysosomes in aged animals. However,
      the cellular roles and mechanisms of LRRK2-mediated lysosomal regulation have
      remained elusive. Here, we reveal a mechanism of stress-induced lysosomal
      response by LRRK2 and its target Rab GTPases. Lysosomal overload stress induced
      the recruitment of endogenous LRRK2 onto lysosomal membranes and activated LRRK2.
      An upstream adaptor Rab7L1 (Rab29) promoted the lysosomal recruitment of LRRK2.
      Subsequent family-wide screening of Rab GTPases that may act downstream of LRRK2
      translocation revealed that Rab8a and Rab10 were specifically accumulated on
      overloaded lysosomes dependent on their phosphorylation by LRRK2. Rab7L1-mediated
      lysosomal targeting of LRRK2 attenuated the stress-induced lysosomal enlargement
      and promoted lysosomal secretion, whereas Rab8 stabilized by LRRK2 on stressed
      lysosomes suppressed lysosomal enlargement and Rab10 promoted lysosomal
      secretion, respectively. These effects were mediated by the recruitment of
      Rab8/10 effectors EHBP1 and EHBP1L1. LRRK2 deficiency augmented the chloroquine
      induced lysosomal vacuolation of renal tubules in vivo. These results implicate
      the stress-responsive machinery composed of Rab7L1, LRRK2, phosphorylated
      Rab8/10, and their downstream effectors in the maintenance of lysosomal
      homeostasis.

PMID- 30209222
TI  - Local root growth and death are mediated by contrasts in nutrient availability
      and root quantity between soil patches.
AB  - Plants are thought to be able to regulate local root growth according to its
      overall nutrient status as well as nutrient contents in a local substrate patch.
      Therefore, root plastic responses to environmental changes are probably co
      determined by local responses of root modules and systematic control of the whole
      plant. Recent studies showed that the contrast in nutrient availability between
      different patches could significantly influence the growth and death of local
      roots. In this study, we further explored, beside nutrient contrast, whether root
      growth and death in a local patch are also affected by relative root quantity in
      the patch. We conducted a split-root experiment with different splitting ratios
      of roots of Canada goldenrod (Solidago canadensis) individuals, as well as high-
      (5* Hoagland solution versus water) or low- (1* Hoagland solution versus water)
      contrast nutrient conditions for the split roots. The results showed that root
      growth decreased in nutrient-rich patches but increased in nutrient-poor patches
      when more roots co-occurred in the same patches, irrespective of nutrient
      contrast condition. Root mortality depended on contrasts in both root quantity
      and nutrients: in the high-nutrient-contrast condition, it increased in nutrient
      rich patches but decreased in nutrient-poor patches with increasing root
      proportion; while in the low-nutrient-contrast condition, it showed the opposite
      trend. These results demonstrated that root growth and death dynamics were
      affected by the contrast in both nutrient availability and root quantity between
      patches. Our study provided ecological evidence that local root growth and death
      are mediated by both the responses of root modules to a nutrient patch and the
      whole-plant nutrient status, suggesting that future work investigating root
      production and turnover should take into account the degree of heterogeneity in
      nutrient and root distribution.

PMID- 30209221
TI  - Bighead is a Wnt antagonist secreted by the Xenopus Spemann organizer that
      promotes Lrp6 endocytosis.
AB  - The Xenopus laevis embryo has been subjected to almost saturating screens for
      molecules specifically expressed in dorsal Spemann organizer tissue. In this
      study, we performed high-throughput RNA sequencing of ectodermal explants, called
      animal caps, which normally give rise to epidermis. We analyzed dissociated
      animal cap cells that, through sustained activation of MAPK, differentiate into
      neural tissue. We also microinjected mRNAs for Cerberus, Chordin, FGF8, BMP4,
      Wnt8, and Xnr2, which induce neural or other germ layer differentiations. The
      searchable database provided here represents a valuable resource for the early
      vertebrate cell differentiation. These analyses resulted in the identification of
      a gene present in frog and fish, which we call Bighead. Surprisingly, at
      gastrula, it was expressed in the Spemann organizer and endoderm, rather than in
      ectoderm as we expected. Despite the plethora of genes already mined from Spemann
      organizer tissue, Bighead encodes a secreted protein that proved to be a potent
      inhibitor of Wnt signaling in a number of embryological and cultured cell
      signaling assays. Overexpression of Bighead resulted in large head structures
      very similar to those of the well-known Wnt antagonists Dkk1 and Frzb-1.
      Knockdown of Bighead with specific antisense morpholinos resulted in embryos with
      reduced head structures, due to increased Wnt signaling. Bighead protein bound
      specifically to the Wnt coreceptor lipoprotein receptor-related protein 6 (Lrp6),
      leading to its removal from the cell surface. Bighead joins two other Wnt
      antagonists, Dkk1 and Angptl4, which function as Lrp6 endocytosis regulators.
      These results suggest that endocytosis plays a crucial role in Wnt signaling.

PMID- 30209223
TI  - Nonlinear averaging of thermal experience predicts population growth rates in a
      thermally variable environment.
AB  - As thermal regimes change worldwide, projections of future population and species
      persistence often require estimates of how population growth rates depend on
      temperature. These projections rarely account for how temporal variation in
      temperature can systematically modify growth rates relative to projections based
      on constant temperatures. Here, we tested the hypothesis that time-averaged
      population growth rates in fluctuating thermal environments differ from growth
      rates in constant conditions as a consequence of Jensen's inequality, and that
      the thermal performance curves (TPCs) describing population growth in fluctuating
      environments can be predicted quantitatively based on TPCs generated in constant
      laboratory conditions. With experimental populations of the green alga
      Tetraselmis tetrahele, we show that nonlinear averaging techniques accurately
      predicted increased as well as decreased population growth rates in fluctuating
      thermal regimes relative to constant thermal regimes. We extrapolate from these
      results to project critical temperatures for population growth and persistence of
      89 phytoplankton species in naturally variable thermal environments. These
      results advance our ability to predict population dynamics in the context of
      global change.

PMID- 30209224
TI  - Ecological specialization is associated with genetic structure in the ant
      associated butterfly family Lycaenidae.
AB  - The role of specialization in diversification can be explored along two
      geological axes in the butterfly family Lycaenidae. In addition to variation in
      host-plant specialization normally exhibited by butterflies, the caterpillars of
      most Lycaenidae have symbioses with ants ranging from no interactions through to
      obligate and specific associations, increasing niche dimensionality in ant
      associated taxa. Based on mitochondrial sequences from 8282 specimens from 967
      species and 249 genera, we show that the degree of ecological specialization of
      lycaenid species is positively correlated with genetic divergence, haplotype
      diversity and an increase in isolation by distance. Nucleotide substitution rate
      is higher in carnivorous than phytophagous lycaenids. The effects documented here
      for both micro- and macroevolutionary processes could result from increased
      spatial segregation as a consequence of reduced connectivity in specialists,
      niche-based divergence or a combination of both. They could also provide an
      explanation for the extraordinary diversity of the Lycaenidae and, more
      generally, for diversity in groups of organisms with similar multi-dimensional
      ecological specialization.

PMID- 30209225
TI  - Stratigraphic signatures of mass extinctions: ecological and sedimentary
      determinants.
AB  - Stratigraphic patterns of last occurrences (LOs) of fossil taxa potentially
      fingerprint mass extinctions and delineate rates and geometries of those events.
      Although empirical studies of mass extinctions recognize that random sampling
      causes LOs to occur earlier than the time of extinction (Signor-Lipps effect),
      sequence stratigraphic controls on the position of LOs are rarely considered. By
      tracing stratigraphic ranges of extant mollusc species preserved in the Holocene
      succession of the Po coastal plain (Italy), we demonstrated that, if mass
      extinction took place today, complex but entirely false extinction patterns would
      be recorded regionally due to shifts in local community composition and non
      random variation in the abundance of skeletal remains, both controlled by
      relative sea-level changes. Consequently, rather than following an apparent
      gradual pattern expected from the Signor-Lipps effect, LOs concentrated within
      intervals of stratigraphic condensation and strong facies shifts mimicking sudden
      extinction pulses. Methods assuming uniform recovery potential of fossils falsely
      supported stepwise extinction patterns among studied species and systematically
      underestimated their stratigraphic ranges. Such effects of stratigraphic
      architecture, co-produced by ecological, sedimentary and taphonomic processes,
      can easily confound interpretations of the timing, duration and selectivity of
      mass extinction events. Our results highlight the necessity of accounting for
      palaeoenvironmental and sequence stratigraphic context when inferring extinction
      dynamics from the fossil record.

PMID- 30209226
TI  - Parent-offspring facial resemblance increases with age in rhesus macaques.
AB  - Kin recognition is a key ability which facilitates the acquisition of inclusive
      fitness benefits and enables optimal outbreeding. In primates, phenotype matching
      is considered particularly important for the recognition of patrilineal
      relatives, as information on paternity is unlikely to be available via social
      familiarity. Phenotypic cues to both paternal and maternal relatedness exist in
      the facial features of humans and other primates. However, theoretical models
      suggest that in systems with uncertainty parentage it may be adaptive for
      offspring to conceal such cues when young, in order to avoid potential costs of
      being discriminated against by unrelated adults. Using experienced human raters,
      we demonstrate in a computer-based task that detection of parent-offspring
      resemblances in the faces of rhesus macaques (Macaca mulatta) increases
      significantly with offspring age. Moreover, this effect is specific to
      information about kinship, as raters were extremely successful at discriminating
      individuals even among the youngest animals. To our knowledge, this is the first
      evidence in non-humans for the age-dependent expression of visual cues used in
      kin recognition.

PMID- 30209227
TI  - How does parental environment influence the potential for adaptation to global
      change?
AB  - Parental environments are regularly shown to alter the mean fitness of offspring,
      but their impacts on the genetic variation for fitness, which predicts adaptive
      capacity and is also measured on offspring, are unclear. Consequently, how
      parental environments mediate adaptation to environmental stressors, like those
      accompanying global change, is largely unknown. Here, using an ecologically
      important marine tubeworm in a quantitative-genetic breeding design, we tested
      how parental exposure to projected ocean warming alters the mean survival, and
      genetic variation for survival, of offspring during their most vulnerable life
      stage under current and projected temperatures. Offspring survival was higher
      when parent and offspring temperatures matched. Across offspring temperatures,
      parental exposure to warming altered the distribution of additive genetic
      variance for survival, making it covary across current and projected temperatures
      in a way that may aid adaptation to future warming. Parental exposure to warming
      also amplified nonadditive genetic variance for survival, suggesting that
      compatibilities between parental genomes may grow increasingly important under
      future warming. Our study shows that parental environments potentially have
      broader-ranging effects on adaptive capacity than currently appreciated, not only
      mitigating the negative impacts of global change but also reshaping the raw fuel
      for evolutionary responses to it.

PMID- 30209228
TI  - Maternal reproductive senescence shapes the fitness consequences of the parental
      age difference in ruffed lemurs.
AB  - In humans, pronounced age differences between parents have deleterious fitness
      consequences. In particular, the number of children is lower when mothers are
      much older than fathers. However, previous analyses failed to disentangle the
      influence of differential parental age per se from a direct age effect of each
      parent. In this study, we analyse the fitness consequences of both parental age
      and parental age differences on litter size and offspring survival in two closely
      related species of lemurs living in captivity. As captive lemurs do not choose
      their reproductive partner, we were able to measure litter size and offspring
      survival across breeding pairs showing a wide range of parental age differences.
      However, we demonstrated that the effect of the parental age difference on litter
      size was fully accounted for by female reproductive senescence because females
      mating with much younger males were old females. On the other hand, both parental
      age difference and female reproductive senescence influenced offspring survival.
      Our results emphasize the importance of teasing apart the effect of parental
      reproductive senescence when investigating the health and fitness consequences of
      parental age differences and also provide new insights for conservation
      programmes of endangered species.

PMID- 30209229
TI  - The scent of attractiveness: levels of reproductive hormones explain individual
      differences in women's body odour.
AB  - Individuals are thought to have their own distinctive body odour which reportedly
      plays an important role in mate choice. In the present study we investigated
      individual differences in body odours of women and examined whether some women
      generally smell more attractive than others or whether odour preferences are a
      matter of individual taste. We then explored whether levels of reproductive
      hormones explain women's body odour attractiveness, to test the idea that body
      odour attractiveness may act as a chemosensory marker of reproductive fitness.
      Fifty-seven men rated body odours of 28 healthy, naturally cycling women of
      reproductive age. We collected all odours at peak fertility to control for
      menstrual cycle effects on body odour attractiveness. Women's salivary
      oestradiol, progesterone, testosterone and cortisol levels were assessed at the
      time of odour collection to test whether hormone levels explain body odour
      attractiveness. We found that the men highly agreed on how attractive they found
      women's body odours. Interestingly, women's body odour attractiveness was
      predicted by their oestradiol and progesterone levels: the higher a woman's
      levels of oestradiol and the lower her levels of progesterone, the more
      attractive her body odour was rated. In showing that women's body odour
      attractiveness is explained by levels of female reproductive hormones, but not by
      levels of cortisol or testosterone, we provide evidence that body odour acts as a
      valid cue to potential fertility.

PMID- 30209231
TI  - Divergence in sex peptide-mediated female post-mating responses in Drosophila
      melanogaster.
AB  - Transfer and receipt of seminal fluid proteins crucially affect reproductive
      processes in animals. Evolution in these male ejaculatory proteins is explained
      with post-mating sexual selection, but we lack a good understanding of the
      evolution of female post-mating responses (PMRs) to these proteins. Some of these
      proteins are expected to mediate sexually antagonistic coevolution generating the
      expectation that females evolve resistance. One candidate in Drosophila
      melanogaster is the sex peptide (SP) which confers cost of mating in females. In
      this paper, we compared female SP-induced PMRs across three D. melanogaster wild
      type populations after mating with SP-lacking versus control males including
      fitness measures. Surprisingly, we did not find any evidence for SP-mediated
      fitness costs in any of the populations. However, female lifetime reproductive
      success and lifespan were differently affected by SP receipt indicating that
      female PMRs diverged among populations. Injection of synthetic SP into virgin
      females further supported these findings and suggests that females from different
      populations require different amounts of SP to effectively initiate PMRs.
      Molecular analyses of the SP receptor suggest that genetic differences might
      explain the observed phenotypical divergence. We discuss the evolutionary
      processes that might have caused this divergence in female PMRs.

PMID- 30209233
TI  - It's time to stop saying "the mind is unaffected" in ALS.

PMID- 30209230
TI  - Bonobos voluntarily hand food to others but not toys or tools.
AB  - A key feature of human prosociality is direct transfers, the most active form of
      sharing in which donors voluntarily hand over resources in their possession
      Direct transfers buffer hunter-gatherers against foraging shortfalls. The
      emergence and elaboration of this behaviour thus likely played a key role in
      human evolution by promoting cooperative interdependence and ensuring that
      humans' growing energetic needs (e.g. for increasing brain size) were more
      reliably met. According to the strong prosociality hypothesis, among great apes
      only humans exhibit sufficiently strong prosocial motivations to directly
      transfer food. The versatile prosociality hypothesis suggests instead that while
      other apes may make transfers in constrained settings, only humans share flexibly
      across food and non-food contexts. In controlled experiments, chimpanzees
      typically transfer objects but not food, supporting both hypotheses. In this
      paper, we show in two experiments that bonobos directly transfer food but not non
      food items. These findings show that, in some contexts, bonobos exhibit a human
      like motivation for direct food transfer. However, humans share across a far
      wider range of contexts, lending support to the versatile prosociality
      hypothesis. Our species' unusual prosocial flexibility is likely built on a
      prosocial foundation we share through common descent with the other apes.

PMID- 30209232
TI  - Human-like Cmah inactivation in mice increases running endurance and decreases
      muscle fatigability: implications for human evolution.
AB  - Compared to other primates, humans are exceptional long-distance runners, a
      feature that emerged in genus Homo approximately 2 Ma and is classically
      attributed to anatomical and physiological adaptations such as an enlarged
      gluteus maximus and improved heat dissipation. However, no underlying genetic
      changes have currently been defined. Two to three million years ago, an exon
      deletion in the CMP-Neu5Ac hydroxylase (CMAH) gene also became fixed in our
      ancestral lineage. Cmah loss in mice exacerbates disease severity in multiple
      mouse models for muscular dystrophy, a finding only partially attributed to
      differences in immune reactivity. We evaluated the exercise capacity of Cmah-/-
      mice and observed an increased performance during forced treadmill testing and
      after 15 days of voluntary wheel running. Cmah-/- hindlimb muscle exhibited more
      capillaries and a greater fatigue resistance in situ Maximal coupled respiration
      was also higher in Cmah null mice ex vivo and relevant differences in metabolic
      pathways were also noted. Taken together, these data suggest that CMAH loss
      contributes to an improved skeletal muscle capacity for oxygen use. If
      translatable to humans, CMAH loss could have provided a selective advantage for
      ancestral Homo during the transition from forest dwelling to increased resource
      exploration and hunter/gatherer behaviour in the open savannah.

PMID- 30209234
TI  - Glial fibrillary acidic protein elevations relate to neuroimaging abnormalities
      after mild TBI.
AB  - OBJECTIVES: To determine whether a panel of blood-based biomarkers can
      discriminate between patients with suspected mild traumatic brain injury (mTBI)
      with and without neuroimaging findings (CT and MRI). METHODS: Study participants
      presented to the emergency department with suspected mTBI (n = 277) with a CT and
      MRI scan and healthy controls (n = 49). Plasma concentrations of tau, glial
      fibrillary acidic protein (GFAP), ubiquitin carboxyl-terminal hydrolase L1, and
      neurofilament light chain (NFL) were measured using the single-molecule array
      technology. RESULTS: Concentrations of GFAP, tau, and NFL were higher in patients
      with mTBI, compared with those of controls (p's < 0.01). GFAP yielded an area
      under the curve (AUC) of 0.93 (95% confidence interval [CI] 0.90-0.96),
      confirming its discriminatory power for distinguishing mTBI from controls. Levels
      of GFAP, tau, and NFL were higher in patients with trauma-related intracranial
      findings on CT compared with those with normal CT, with the only significant
      predictor being GFAP (AUC 0.77, 95% CI 0.70-0.84). Among patients with mTBI, tau,
      NFL, and GFAP differentiated subjects with and without MRI abnormalities with an
      AUC of 0.83, with GFAP being the strongest predictor. Combining tau, NFL, and
      GFAP showed a good discriminatory power (AUC 0.80, 95% CI 0.69-0.90) for
      detecting MRI abnormalities, even in patients with mTBI with a normal CT.
      CONCLUSION: Our study confirms GFAP as a promising marker of brain injury in
      patients with acute mTBI. A combination of various biomarkers linked to different
      pathophysiologic mechanisms increases diagnostic subgroup accuracy. This
      multimarker strategy may guide medical decision making, facilitate the use of MRI
      scanning, and prove valuable in the stratification of patients with brain
      injuries in future clinical trials. CLASSIFICATION OF EVIDENCE: Class I evidence
      that blood concentrations of GFAP, tau, and NFL discriminate patients with mTBI
      with and without neuroimaging findings.

PMID- 30209237
TI  - Immediate vs delayed treatment of first unprovoked seizure: To treat, or not to
      treat?

PMID- 30209235
TI  - Serum neurofilament light chain in behavioral variant frontotemporal dementia.
AB  - OBJECTIVE: To determine the association of serum neurofilament light chain (NfL)
      with functional deterioration and brain atrophy during follow-up of patients with
      behavioral variant frontotemporal dementia (bvFTD). METHODS: Blood NfL levels
      from 74 patients with bvFTD, 26 with Alzheimer disease (AD), 17 with mild
      cognitive impairment (MCI), and 15 healthy controls (Con) at baseline and follow
      up were determined and analyzed for the diagnostic potential in relation to
      functional assessment (Clinical Dementia Rating Scale Sum of Boxes [CDR-SOB],
      frontotemporal lobar degeneration-related CDR-SOB, Mini-Mental State Examination
      [MMSE]) and brain volumetry. RESULTS: At baseline, serum NfL level correlated
      with CSF NfL (bvFTD r = 0.706, p < 0.0001; AD/MCI r = 0.666, p = 0.0003). Highest
      serum levels were observed in bvFTD (p <0 0.0001 vs Con and MCI, p = 0.0078 vs
      AD, respectively). Discrimination of bvFTD from Con/MCI/AD was possible with
      91%/74%/74% sensitivity and 79%/74%/58% specificity. At follow-up, serum NfL
      increased in bvFTD and AD (p = 0.0039 and p = 0.0006, respectively). At baseline
      and follow-up, NfL correlated with functional scores of patients with bvFTD
      (e.g., CDR-SOB [baseline] r = 0.4157, p = 0.0006; [follow-up] r = 0.5629, p <
      0.0001) and with atrophy in the gray and white matter of many brain regions
      including frontal and subcortical areas (e.g., frontal lobe: r = -0.5857, p <
      0.0001; 95% confidence interval -0.7415 to -0.3701). For patients with AD/MCI,
      NfL correlated with the functional performance as well (e.g., CDR-SOB [baseline]
      r = 0.6624, p < 0.0001; [follow-up] r = 0.5659, p = 0.0003) but not with regional
      brain volumes. CONCLUSIONS: As serum NfL correlates with functional impairment
      and brain atrophy in bvFTD at different disease stages, we propose it as marker
      of disease severity, paving the way for its future use as outcome measure for
      clinical trials. CLASSIFICATION OF EVIDENCE: This study provides Class III
      evidence that for patients with cognitive problems, serum NfL concentration
      discriminates bvFTD from other forms of dementia.

PMID- 30209236
TI  - ALS-specific cognitive and behavior changes associated with advancing disease
      stage in ALS.
AB  - OBJECTIVE: To elucidate the relationship between disease stage in amyotrophic
      lateral sclerosis (ALS), as measured with the King's Clinical Staging System, and
      cognitive and behavioral change, measured with the Edinburgh Cognitive and
      Behavioural ALS Screen (ECAS). METHODS: A large multicenter observational cohort
      of 161 cross-sectional patients with ALS and 80 healthy matched controls were
      recruited across 3 research sites (Dublin, Edinburgh, and London). Participants
      were administered the ECAS and categorized into independent groups based on their
      King's clinical disease stage at time of testing. RESULTS: Significant
      differences were observed between patients and controls on all subtests of the
      ECAS except for visuospatial functioning. A significant cross-sectional effect
      was observed across disease stages for ALS-specific functions (executive,
      language, letter fluency) and ECAS total score but not for ALS-nonspecific
      functions (memory, visuospatial). Rates of ALS-specific impairment and behavioral
      change were also related to disease stage. The relationship between cognitive
      function and disease stage may be due to letter fluency impairment, whereas
      higher rates of all behavioral domains were seen in later King's stage. The
      presence of bulbar signs, but not site of onset, was significantly related to ALS
      specific, ECAS total, and behavioral scores. CONCLUSION: ALS-specific cognitive
      deficits and behavioral impairment are more frequent with more severe disease
      stage. By end-stage disease, only a small percentage of patients are free of
      neuropsychological impairment. The presence of bulbar symptoms exaggerates the
      differences observed between disease stages. These findings suggest that
      cognitive and behavioral change should be incorporated into ALS diagnostic
      criteria and should be included in future staging systems.

PMID- 30209238
TI  - Enzyme replacement therapy and white matter hyperintensity progression in Fabry
      disease.
AB  - OBJECTIVE: To explore the association between enzyme replacement therapy (ERT),
      clinical characteristics, and the rate of progression of white matter
      hyperintensities (WMH) in patients with Fabry disease (FD). METHODS: Patients
      with a confirmed diagnosis of FD, aged 18 years or older, participating in an
      existing FD observational study (NCT00196742), with at least 2 serial MRI brain
      scans at least 2 years apart for the period between December 2006 and August 2016
      were included in this cohort study. Total WMH volume was estimated for each image
      using a semiautomated procedure. We performed linear regression to calculate the
      primary outcome measure of WMH change rate for each participant. Associations
      between ERT, clinical characteristics, and the primary outcome were explored
      using multiple linear regression. RESULTS: Eight hundred sixty-three MRI time
      points were analyzed for the 149 included participants. Age (p < 0.0005;
      increasing age associated with faster WMH progression), total cholesterol (p =
      0.03; increasing total cholesterol associated with slower WMH progression), and a
      history of peripheral pain (p = 0.02; peripheral pain associated with faster WMH
      progression) were independently associated with WMH change rate in the primary
      analysis. We did not find an association between "ERT at any point between
      baseline and final MRI" and WMH change rate (p = 0.22). CONCLUSION: In a large
      cohort of patients with FD, we did not find an association between ERT and WMH
      progression, while higher total cholesterol was associated with slower WMH
      progression. Further research is needed into the pathogenesis and treatment of
      cerebrovascular disease in this rare condition.

PMID- 30209239
TI  - Antiepileptic drug treatment after an unprovoked first seizure: A decision
      analysis.
AB  - OBJECTIVE: To compare the expected quality-adjusted life-years (QALYs) in adult
      patients undergoing immediate vs deferred antiepileptic drug (AED) treatment
      after a first unprovoked seizure. METHODS: We constructed a simulated clinical
      trial (Markov decision model) to compare immediate vs deferred AED treatment
      after a first unprovoked seizure in adults. Three base cases were considered,
      representing patients with varying degrees of seizure recurrence risk and effect
      of seizures on quality of life (QOL). Cohort simulation was performed to
      determine which treatment strategy would maximize the patient's expected QALYs.
      Sensitivity analyses were guided by clinical data to define decision thresholds
      across plausible measurement ranges, including seizure recurrence rate, effect of
      seizure recurrence on QOL, and efficacy of AEDs. RESULTS: For patients with a
      moderate risk of recurrent seizures (52.0% over 10 years after first seizure),
      immediate AED treatment maximized QALYs compared to deferred treatment.
      Sensitivity analyses showed that for the preferred choice to change to deferred
      AED treatment, key clinical measures needed to reach implausible values were 10
      year seizure recurrence rate <=38.0%, QOL reduction with recurrent seizures
      <=0.06, and efficacy of AEDs on lowering seizure recurrence rate <=16.3%.
      CONCLUSION: Our model determined that immediate AED treatment is preferable to
      deferred treatment in adult first-seizure patients over a wide and clinically
      relevant range of variables. Furthermore, our analysis suggests that the 10-year
      seizure recurrence rate that justifies AED treatment (38.0%) is substantially
      lower than the 60% threshold used in the current definition of epilepsy.

PMID- 30209241
TI  - Targeting the Warburg effect via LDHA inhibition engages ATF4 signaling for
      cancer cell survival.
AB  - Nutrient restriction reprograms cellular signaling and metabolic network to shape
      cancer phenotype. Lactate dehydrogenase A (LDHA) has a key role in aerobic
      glycolysis (the Warburg effect) through regeneration of the electron acceptor
      NAD+ and is widely regarded as a desirable target for cancer therapeutics.
      However, the mechanisms of cellular response and adaptation to LDHA inhibition
      remain largely unknown. Here, we show that LDHA activity supports serine and
      aspartate biosynthesis. Surprisingly, however, LDHA inhibition fails to impact
      human melanoma cell proliferation, survival, or tumor growth. Reduced
      intracellular serine and aspartate following LDHA inhibition engage GCN2-ATF4
      signaling to initiate an expansive pro-survival response. This includes the
      upregulation of glutamine transporter SLC1A5 and glutamine uptake, with
      concomitant build-up of essential amino acids, and mTORC1 activation, to
      ameliorate the effects of LDHA inhibition. Tumors with low LDHA expression and
      melanoma patients acquiring resistance to MAPK signaling inhibitors, which target
      the Warburg effect, exhibit altered metabolic gene expression reminiscent of the
      ATF4-mediated survival signaling. ATF4-controlled survival mechanisms conferring
      synthetic vulnerability to the approaches targeting the Warburg effect offer
      efficacious therapeutic strategies.

PMID- 30209243
TI  - Evaluation of mutant huntingtin and neurofilament proteins as potential markers
      in Huntington's disease.
AB  - Huntington's disease (HD) is a genetic progressive neurodegenerative disorder,
      caused by a mutation in the HTT gene, for which there is currently no cure. The
      identification of sensitive indicators of disease progression and therapeutic
      outcome could help the development of effective strategies for treating HD. We
      assessed mutant huntingtin (mHTT) and neurofilament light (NfL) protein
      concentrations in cerebrospinal fluid (CSF) and blood in parallel with clinical
      evaluation and magnetic resonance imaging in premanifest and manifest HD mutation
      carriers. Among HD mutation carriers, NfL concentrations in plasma and CSF
      correlated with all nonbiofluid measures more closely than did CSF mHTT
      concentration. Longitudinal analysis over 4 to 8 weeks showed that CSF mHTT, CSF
      NfL, and plasma NfL concentrations were highly stable within individuals. In our
      cohort, concentration of CSF mHTT accurately distinguished between controls and
      HD mutation carriers, whereas NfL concentration, in both CSF and plasma, was able
      to segregate premanifest from manifest HD. In silico modeling indicated that mHTT
      and NfL concentrations in biofluids might be among the earliest detectable
      alterations in HD, and sample size prediction suggested that low participant
      numbers would be needed to incorporate these measures into clinical trials. These
      findings provide evidence that biofluid concentrations of mHTT and NfL have
      potential for early and sensitive detection of alterations in HD and could be
      integrated into both clinical trials and the clinic.

PMID- 30209242
TI  - Sarcoplasmic reticulum calcium leak contributes to arrhythmia but not to heart
      failure progression.
AB  - Increased sarcoplasmic reticulum (SR) Ca2+ leak via the cardiac ryanodine
      receptor (RyR2) has been suggested to play a mechanistic role in the development
      of heart failure (HF) and cardiac arrhythmia. Mice treated with a selective RyR2
      stabilizer, rycal S36, showed normalization of SR Ca2+ leak and improved survival
      in pressure overload (PO) and myocardial infarction (MI) models. The development
      of HF, measured by echocardiography and molecular markers, showed no difference
      in rycal S36- versus placebo-treated mice. Reduction of SR Ca2+ leak in the PO
      model by the rycal-unrelated RyR2 stabilizer dantrolene did not mitigate HF
      progression. Development of HF was not aggravated by increased SR Ca2+ leak due
      to RyR2 mutation (R2474S) in volume overload, an SR Ca2+ leak-independent HF
      model. Arrhythmia episodes were reduced by rycal S36 treatment in PO and MI mice
      in vivo and ex vivo in Langendorff-perfused hearts. Isolated cardiomyocytes from
      murine failing hearts and human ventricular failing and atrial nonfailing
      myocardium showed reductions in delayed afterdepolarizations, in spontaneous and
      induced Ca2+ waves, and in triggered activity in rycal S36 versus placebo cells,
      whereas the Ca2+ transient, SR Ca2+ load, SR Ca2+ adenosine triphosphatase
      function, and action potential duration were not affected. Rycal S36 treatment of
      human induced pluripotent stem cells isolated from a patient with
      catecholaminergic polymorphic ventricular tachycardia could rescue the leaky RyR2
      receptor. These results suggest that SR Ca2+ leak does not primarily influence
      contractile HF progression, whereas rycal S36 treatment markedly reduces
      ventricular arrhythmias, thereby improving survival in mice.

PMID- 30209244
TI  - ANP32A regulates ATM expression and prevents oxidative stress in cartilage,
      brain, and bone.
AB  - Osteoarthritis is the most common joint disorder with increasing global
      prevalence due to aging of the population. Current therapy is limited to symptom
      relief, yet there is no cure. Its multifactorial etiology includes oxidative
      stress and overproduction of reactive oxygen species, but the regulation of these
      processes in the joint is insufficiently understood. We report that ANP32A
      protects the cartilage against oxidative stress, preventing osteoarthritis
      development and disease progression. ANP32A is down-regulated in human and mouse
      osteoarthritic cartilage. Microarray profiling revealed that ANP32A protects the
      joint by promoting the expression of ATM, a key regulator of the cellular
      oxidative defense. Antioxidant treatment reduced the severity of osteoarthritis,
      osteopenia, and cerebellar ataxia features in Anp32a-deficient mice, revealing
      that the ANP32A/ATM axis discovered in cartilage is also present in brain and
      bone. Our findings indicate that modulating ANP32A signaling could help manage
      oxidative stress in cartilage, brain, and bone with therapeutic implications for
      osteoarthritis, neurological disease, and osteoporosis.

PMID- 30209240
TI  - Hypothalamic CNTF volume transmission shapes cortical noradrenergic excitability
      upon acute stress.
AB  - Stress-induced cortical alertness is maintained by a heightened excitability of
      noradrenergic neurons innervating, notably, the prefrontal cortex. However,
      neither the signaling axis linking hypothalamic activation to delayed and lasting
      noradrenergic excitability nor the molecular cascade gating noradrenaline
      synthesis is defined. Here, we show that hypothalamic corticotropin-releasing
      hormone-releasing neurons innervate ependymal cells of the 3rd ventricle to
      induce ciliary neurotrophic factor (CNTF) release for transport through the
      brain's aqueductal system. CNTF binding to its cognate receptors on
      norepinephrinergic neurons in the locus coeruleus then initiates sequential
      phosphorylation of extracellular signal-regulated kinase 1 and tyrosine
      hydroxylase with the Ca2+-sensor secretagogin ensuring activity dependence in
      both rodent and human brains. Both CNTF and secretagogin ablation occlude stress
      induced cortical norepinephrine synthesis, ensuing neuronal excitation and
      behavioral stereotypes. Cumulatively, we identify a multimodal pathway that is
      rate-limited by CNTF volume transmission and poised to directly convert
      hypothalamic activation into long-lasting cortical excitability following acute
      stress.

PMID- 30209245
TI  - A database of tissue-specific rhythmically expressed human genes has potential
      applications in circadian medicine.
AB  - The discovery that half of the mammalian protein-coding genome is regulated by
      the circadian clock has clear implications for medicine. Recent studies
      demonstrated that the circadian clock influences therapeutic outcomes in human
      heart disease and cancer. However, biological time is rarely given clinical
      consideration. A key barrier is the absence of information on tissue-specific
      molecular rhythms in the human body. We have applied the cyclic ordering by
      periodic structure (CYCLOPS) algorithm, designed to reconstruct sample temporal
      order in the absence of time-of-day information, to the gene expression
      collection of 13 tissues from 632 human donors. We identified rhythms in gene
      expression across the body; nearly half of protein-coding genes were shown to be
      cycling in at least 1 of the 13 tissues analyzed. One thousand of these cycling
      genes encode proteins that either transport or metabolize drugs or are themselves
      drug targets. These results provide a useful resource for studying the role of
      circadian rhythms in medicine and support the idea that biological time might
      play a role in determining drug response.

PMID- 30209246
TI  - Thrombopoietin receptor-independent stimulation of hematopoietic stem cells by
      eltrombopag.
AB  - Eltrombopag (EP), a small-molecule thrombopoietin receptor (TPO-R) agonist and
      potent intracellular iron chelator, has shown remarkable efficacy in stimulating
      sustained multilineage hematopoiesis in patients with bone marrow failure
      syndromes, suggesting an effect at the most immature hematopoietic stem and
      multipotent progenitor level. Although the functional and molecular effects of EP
      on megakaryopoiesis have been studied in the past, mechanistic insights into its
      effects on the earliest stages of hematopoiesis have been limited. We
      investigated the effects of EP treatment on hematopoietic stem cell (HSC)
      function using purified primary HSCs in separation-of-function mouse models,
      including a TPO-R-deficient strain, and stem cells isolated from patients
      undergoing TPO-R agonist treatment. Our mechanistic studies showed a stimulatory
      effect on stem cell self-renewal independently of TPO-R. Human and mouse HSCs
      responded to acute EP treatment with metabolic and gene expression alterations
      consistent with a reduction of intracellular labile iron pools that are essential
      for stem cell maintenance. Iron preloading prevented the stem cell stimulatory
      effects of EP. Moreover, comparative analysis of stem cells in the bone marrow of
      patients receiving EP showed a marked increase in the number of functional stem
      cells compared to patients undergoing therapy with romiplostim, another TPO-R
      agonist lacking an iron-chelating ability. Together, our study demonstrates that
      EP stimulates hematopoiesis at the stem cell level through iron chelation
      mediated molecular reprogramming and indicates that labile iron pool-regulated
      pathways can modulate HSC function.

PMID- 30209247
TI  - Use of Pamidronate to Treat Hypercalcemia in an Oncology Dialysis Patient: A Case
      Report.
AB  - BACKGROUND Hypercalcemia is a common complication in the intensive care unit
      (ICU). It can be a result of diverse etiologies, such as malignancy. In this
      case, bisphosphonates can serve as an effective therapeutic option. However,
      bisphosphonates are not safe to use in patients with end stage renal disease.
      CASE REPORT We report a case of severe hypercalcemia possibly secondary to bone
      metastasis. The patient is known to have end-stage renal disease (ESRD) and
      undergoing dialysis 3 times a week. She had severe persistent hypercalcemia which
      did not resolve with regular measures or calcitonin. The literature was searched
      for the possibility of administering bisphosphonate as a treatment option. It was
      found that pamidronate pharmacokinetics can be safe and effective in end-stage
      renal disease patients. Therefore, Pamidronate was administered, showing
      effective results with regards to the level of calcium and no observed adverse
      effects. Re-dosing was required at an 8-week interval, with no adverse effects.
      CONCLUSIONS Pamidronate is a safe option to use in treating hypercalcemia in end
      stage renal disease patients on dialysis. This can be especially beneficial in
      patients with sustained hypercalcemia secondary to malignancy.

PMID- 30209248
TI  - Clinicopathological and Prognostic Significance of Expression of B-Cell-Specific
      Moloney Murine Leukemia Virus Insertion Site 1 (BMI-1) Gene and Protein in
      Gastrointestinal Stromal Tumors.
AB  - BACKGROUND Gastrointestinal stromal tumor (GIST) is an uncommon visceral sarcoma
      that arises predominantly in the gastrointestinal tract. Since GISTs are
      encountered infrequently and inflexible to traditional therapy, the aim of the
      present study was to explore the correlation of B-cell-specific Moloney murine
      leukemia virus insertion site 1 (BMI-1) mRNA and BMI-1 protein levels with the
      clinicopathological characteristics and prognosis significance of GISTs. MATERIAL
      AND METHODS GIST tissues and normal tissues were collected from 156 patients who
      had undergone surgical treatment. RT-qPCR and immunohistochemistry were used to
      measure the BMI-1 mRNA and protein levels in GIST tissues and normal tissues.
      Univariate survival analysis was used for determination of the factors that
      affect prognosis of GIST patients. Cox proportional hazards model was plotted to
      determine the independent risk factors for prognosis of GIST patients. RESULTS
      The BMI-1 mRNA and protein levels in GIST tissues were higher than those in
      normal tissues. BMI-1 mRNA and positive protein levels were correlated with the
      National Institutes of Health (NIH) risk grade, tumor diameter and infiltration,
      and metastasis. There was a short survival period for the patients with a
      positive protein level and a high mRNA level of BMI-1. The site of primary tumor,
      tumor diameter, NIH risk grade, infiltration, and metastasis, as well as BMI-1
      mRNA and protein levels were independent risk factors for prognosis of GIST
      patients. CONCLUSIONS Taken together, these findings suggest there might be a
      relationship between BMI-1 mRNA and protein levels, and clinicopathological
      characteristics, including NIH risk grade, tumor size as well as infiltration and
      metastasis, of GIST patients. In addition, BMI-1 mRNA and protein levels were
      identified as independent risk factors for prognosis of GIST patients.

PMID- 30209249
TI  - Neuronal heterogeneity and stereotyped connectivity in the auditory afferent
      system.
AB  - Spiral ganglion (SG) neurons of the cochlea convey all auditory inputs to the
      brain, yet the cellular and molecular complexity necessary to decode the various
      acoustic features in the SG has remained unresolved. Using single-cell RNA
      sequencing, we identify four types of SG neurons, including three novel
      subclasses of type I neurons and the type II neurons, and provide a comprehensive
      genetic framework that define their potential synaptic communication patterns.
      The connectivity patterns of the three subclasses of type I neurons with inner
      hair cells and their electrophysiological profiles suggest that they represent
      the intensity-coding properties of auditory afferents. Moreover, neuron type
      specification is already established at birth, indicating a neuronal
      diversification process independent of neuronal activity. Thus, this work
      provides a transcriptional catalog of neuron types in the cochlea, which serves
      as a valuable resource for dissecting cell-type-specific functions of dedicated
      afferents in auditory perception and in hearing disorders.

PMID- 30209250
TI  - Recurrent circuits within medial entorhinal cortex superficial layers support
      grid cell firing.
AB  - Specialized cells in the medial entorhinal cortex (mEC), such as speed cells,
      head direction (HD) cells, and grid cells, are thought to support spatial
      navigation. To determine whether these computations are dependent on local
      circuits, we record neuronal activity in mEC layers II and III and
      optogenetically perturb locally projecting layer II pyramidal cells. We find that
      sharply tuned HD cells are only weakly responsive while speed, broadly tuned HD
      cells, and grid cells show pronounced transient excitatory and inhibitory
      responses. During the brief period of feedback inhibition, there is a reduction
      in specifically grid accuracy, which is corrected as firing rates return to
      baseline. These results suggest that sharp HD cells are embedded in a separate
      mEC sub-network from broad HD cells, speed cells, and grid cells. Furthermore,
      grid tuning is not only dependent on local processing but also rapidly updated by
      HD, speed, or other afferent inputs to mEC.

PMID- 30209251
TI  - Evolution of the quantum Hall bulk spectrum into chiral edge states.
AB  - One of the most intriguing and fundamental properties of topological systems is
      the correspondence between the conducting edge states and the gapped bulk
      spectrum. Here, we use a GaAs cleaved edge quantum wire to perform momentum
      resolved spectroscopy of the quantum Hall edge states in a tunnel-coupled 2D
      electron gas. This reveals the momentum and position of the edge states with
      unprecedented precision and shows the evolution from very low magnetic fields all
      the way to high fields where depopulation occurs. We present consistent
      analytical and numerical models, inferring the edge states from the well-known
      bulk spectrum, finding excellent agreement with the experiment-thus providing
      direct evidence for the bulk to edge correspondence. In addition, we observe
      various features beyond the single-particle picture, such as Fermi level pinning,
      exchange-enhanced spin splitting and signatures of edge-state reconstruction.

PMID- 30209253
TI  - Histone H4K20 methylation mediated chromatin compaction threshold ensures genome
      integrity by limiting DNA replication licensing.
AB  - The decompaction and re-establishment of chromatin organization immediately after
      mitosis is essential for genome regulation. Mechanisms underlying chromatin
      structure control in daughter cells are not fully understood. Here we show that a
      chromatin compaction threshold in cells exiting mitosis ensures genome integrity
      by limiting replication licensing in G1 phase. Upon mitotic exit, chromatin
      relaxation is controlled by SET8-dependent methylation of histone H4 on lysine
      20. In the absence of either SET8 or H4K20 residue, substantial genome-wide
      chromatin decompaction occurs allowing excessive loading of the origin
      recognition complex (ORC) in the daughter cells. ORC overloading stimulates
      aberrant recruitment of the MCM2-7 complex that promotes single-stranded DNA
      formation and DNA damage. Restoring chromatin compaction restrains excess
      replication licensing and loss of genome integrity. Our findings identify a cell
      cycle-specific mechanism whereby fine-tuned chromatin relaxation suppresses
      excessive detrimental replication licensing and maintains genome integrity at the
      cellular transition from mitosis to G1 phase.

PMID- 30209252
TI  - Dendritic defect-rich palladium-copper-cobalt nanoalloys as robust
      multifunctional non-platinum electrocatalysts for fuel cells.
AB  - Recently, the development of high-performance non-platinum electrocatalysts for
      fuel cell applications has been gaining attention. Palladium-based nanoalloys are
      considered as promising candidates to substitute platinum catalysts for cathodic
      and anodic reactions in fuel cells. Here, we develop a facile route to synthesize
      dendritic palladium-copper-cobalt trimetallic nanoalloys as robust
      multifunctional electrocatalysts for oxygen reduction and formic acid oxidation.
      To the best of our knowledge, the mass activities of the dendritic Pd59Cu30Co11
      nanoalloy toward oxygen reduction and formic acid oxidation are higher than those
      previously reported for non-platinum metal nanocatalysts. The Pd59Cu30Co11
      nanoalloys also exhibit superior durability for oxygen reduction and formic acid
      oxidation as well as good antimethanol/ethanol interference ability compared to a
      commercial platinum/carbon catalyst. The high performance of the dendritic
      Pd59Cu30Co11 nanoalloys is attributed to a combination of effects, including
      defects, a synergistic effect, change of d-band center of palladium, and surface
      strain.

PMID- 30209255
TI  - In vitro studies on space-conforming self-assembling silk hydrogels as a
      mesenchymal stem cell-support matrix suitable for minimally invasive brain
      application.
AB  - Advanced cell therapies require robust delivery materials and silk is a promising
      contender with a long clinical track record. Our aim was to optimise self
      assembling silk hydrogels as a mesenchymal stem cell (MSC)-support matrix that
      would allow future minimally invasive brain application. We used sonication
      energy to programme the transition of silk (1-5% w/v) secondary structure from a
      random coil to a stable beta-sheet configuration. This allowed fine tuning of
      self-assembling silk hydrogels to achieve space conformity in the absence of any
      silk hydrogel swelling and to support uniform cell distribution as well as cell
      viability. Embedded cells underwent significant proliferation over 14 days in
      vitro, with the best proliferation achieved with 2% w/v hydrogels. Embedded MSCs
      showed significantly better viability in vitro after injection through a 30G
      needle when the gels were in the pre-gelled versus post-gelled state. Silk
      hydrogels (4% w/v) with physical characteristics matching brain tissue were
      visualised in preliminary in vivo experiments to exhibit good space conformity in
      an ischemic cavity (intraluminal thread middle cerebral artery occlusion model)
      in adult male Sprague-Dawley rats (n = 3). This study informs on optimal MSC
      hydrogel matrix conditions for minimally invasive application as a platform for
      future experiments targeting brain repair.

PMID- 30209254
TI  - Chimeric O1K foot-and-mouth disease virus with SAT2 outer capsid as an FMD
      vaccine candidate.
AB  - Foot-and-mouth disease virus (FMDV) is highly contagious and infects cloven
      hoofed domestic livestock leading to foot-and-mouth disease (FMD). FMD outbreaks
      have severe economic impact due to production losses and associated control
      measures. FMDV is found as seven distinct serotypes, but there are numerous
      subtypes within each serotype, and effective vaccines must match the subtypes
      circulating in the field. In addition, the O and Southern African Territories
      (SAT) serotypes, are relatively more thermolabile and their viral capsids readily
      dissociate into non-immunogenic pentameric subunits, which can compromise the
      effectiveness of FMD vaccines. Here we report the construction of a chimeric
      clone between the SAT2 and O serotypes, designed to have SAT2 antigenicity.
      Characterisation of the chimeric virus showed growth kinetics equal to that of
      the wild type SAT2 virus with better thermostability, attributable to changes in
      the VP4 structural protein. Sequence and structural analyses confirmed that no
      changes from SAT2 were present elsewhere in the capsid as a consequence of the
      VP4 changes. Following exposure to an elevated temperature the thermostable SAT2
      O1K chimera induced higher neutralizing-antibody titres in comparison to wild
      type SAT2 virus.

PMID- 30209256
TI  - Thermoresponsive gels containing gold nanoparticles as smart antibacterial and
      wound healing agents.
AB  - Thermoresponsive gels containing gold nanoparticles (AuNPs) were prepared using
      Pluronic(r)127 alone (F1) and with hydroxypropyl methylcellulose (F2) at ratios
      of 15% w/w and 15:1% w/w, respectively. AuNPs were evaluated for particle size,
      zeta-potential, polydispersity index (PDI), morphology and XRD pattern. AuNP
      containing thermoresponsive gels were investigated for their gelation
      temperature, gel strength, bio-adhesive force, viscosity, drug content, in vitro
      release and ex-vivo permeation, in addition to in vitro antibacterial activity
      against bacteria found in burn infections, Staphylococcus aureus. In vivo burn
      healing and antibacterial activities were also investigated and compared with
      those of a commercial product using burn-induced infected wounds in mice.
      Spherical AuNPs sized 28.9-37.65 nm displayed a surface plasmon resonance band at
      522 nm, a PDI of 0.461, and a zeta potential of 34.8 mV with a negative surface
      charge. F1 and F2 showed gelation temperatures of 37.2  degrees C and 32.3 
      degrees C, bio-adhesive forces of 2.45 +/- 0.52 and 4.76 +/- 0.84 dyne/cm2,
      viscosities of 10,165 +/- 1.54 and 14,213 +/- 2.31 cP, and gel strengths between
      7.4 and 10.3 sec, respectively. The in vitro release values of F1 and F2 were
      100% and 98.03% after 6 h, with permeation flux values of (J1) 0.2974 +/- 2.85
      and (J2) 0.2649 +/- 1.43 (ug/cm2.h), respectively. The formulations showed
      antibacterial activity with the highest values for wound healing properties, as
      shown in vivo and by histopathological studies. This study demonstrates that a
      smart AuNPs thermoresponsive gel was successful as an antibacterial and wound
      healing transdermal drug delivery system.

PMID- 30209258
TI  - Improved fragment-based protein structure prediction by redesign of search
      heuristics.
AB  - Difficulty in sampling large and complex conformational spaces remains a key
      limitation in fragment-based de novo prediction of protein structure. Our
      previous work has shown that even for small-to-medium-sized proteins, some
      current methods inadequately sample alternative structures. We have developed two
      new conformational sampling techniques, one employing a bilevel optimisation
      framework and the other employing iterated local search. We combine strategies of
      forced structural perturbation (where some fragment insertions are accepted
      regardless of their impact on scores) and greedy local optimisation, allowing
      greater exploration of the available conformational space. Comparisons against
      the Rosetta Abinitio method indicate that our protocols more frequently generate
      native-like predictions for many targets, even following the low-resolution
      phase, using a given set of fragment libraries. By contrasting results across two
      different fragment sets, we show that our methods are able to better take
      advantage of high-quality fragments. These improvements can also translate into
      more reliable identification of near-native structures in a simple clustering
      based model selection procedure. We show that when fragment libraries are
      sufficiently well-constructed, improved breadth of exploration within runs
      improves prediction accuracy. Our results also suggest that in benchmarking
      scenarios, a total exclusion of fragments drawn from homologous templates can
      make performance differences between methods appear less pronounced.

PMID- 30209257
TI  - MIgGGly (mouse IgG glycosylation analysis) - a high-throughput method for
      studying Fc-linked IgG N-glycosylation in mice with nanoUPLC-ESI-MS.
AB  - Immunoglobulin G (IgG) N-glycosylation is crucial for its effector functions. It
      is a complex trait, and large sample sets are needed to discover multiple genetic
      factors that underlie it. While in humans such high-throughput studies of IgG N
      glycans became usual, only one has been carried out in mice. Here we describe and
      validate a method for the relative quantification of IgG Fc-linked N-glycans in a
      subclass-specific manner using nano-reverse phase liquid chromatography coupled
      with mass-spectrometry (nanoRP-LC-MS) applied to murine IgG. High-throughput data
      processing is ensured by the LaCyTools software. We have shown that IgG isolation
      procedure is the main source of technical variation in the current protocol. The
      major glycoforms were quantified reliably with coefficients of variation below 6%
      for all the analytes with relative abundances above 5%. We have applied our
      method to a sample set of 3 inbred strains: BALB/c, C57BL/6 and C3H and observed
      differences in subclass-specific and strain-specific N-glycosylation of IgG,
      suggesting a significant genetic component in the regulation of Fc-linked IgG N
      glycosylation.

PMID- 30209259
TI  - Increased Phosphaturia Accelerates The Decline in Renal Function: A Search for
      Mechanisms.
AB  - In chronic kidney disease (CKD), high serum phosphate concentration is associated
      with cardiovascular disease and deterioration in renal function. In early CKD,
      the serum phosphate concentration is normal due to increased fractional excretion
      of phosphate. Our premise was that high phosphate intake even in patients with
      early CKD would result in an excessive load of phosphate causing tubular injury
      and accelerating renal function deterioration. In CKD 2-3 patients, we evaluated
      whether increased phosphaturia accelerates CKD progression. To have a uniform
      group of patients with early CKD, 95 patients with metabolic syndrome without
      overt proteinuria were followed for 2.7 +/- 1.6 years. The median decline in eGFR
      was 0.50 ml/min/1.73 m2/year. Patients with a more rapid decrease in eGFR had
      greater phosphaturia. Moreover, the rate of decrease in eGFR inversely correlated
      with the degree of phosphaturia. Additionally, phosphaturia independently
      predicted renal function deterioration. In heminephrectomized rats, a high
      phosphate diet increased phosphaturia resulting in renal tubular damage
      associated with inflammation, oxidative stress and low klotho expression.
      Moreover, in rats with hyperphosphatemia and metabolic syndrome antioxidant
      treatment resulted in attenuation of renal lesions. In HEK-293 cells, high
      phosphate promoted oxidative stress while melatonin administration reduced ROS
      generation. Our findings suggest that phosphate loading in early CKD, results in
      renal damage and a more rapid decrease in renal function due to renal tubular
      injury.

PMID- 30209260
TI  - DaReUS-Loop: accurate loop modeling using fragments from remote or unrelated
      proteins.
AB  - Despite efforts during the past decades, loop modeling remains a difficult part
      of protein structure modeling. Several approaches have been developed in the
      framework of crystal structures. However, for homology models, the modeling of
      loops is still far from being solved. We propose DaReUS-Loop, a data-based
      approach that identifies loop candidates mining the complete set of experimental
      structures available in the Protein Data Bank. Candidate filtering relies on
      local conformation profile-profile comparison, together with physico-chemical
      scoring. Applied to three different template-based test sets, DaReUS-Loop shows
      significant increase in the number of high-accuracy loops, and significant
      enhancement for modeling long loops. A special advantage is that our method
      proposes a prediction confidence score that correlates well with the expected
      accuracy of the loops. Strikingly, over 50% of successful loop models are derived
      from unrelated proteins, indicating that fragments under similar constraints tend
      to adopt similar structure, beyond mere homology.

PMID- 30209262
TI  - Strike-slip 23 January 2018 MW 7.9 Gulf of Alaska rare intraplate earthquake:
      Complex rupture of a fracture zone system.
AB  - Large intraplate earthquakes in oceanic lithosphere are rare and usually related
      to regions of diffuse deformation within the oceanic plate. The 23 January 2018
      MW 7.9 strike-slip Gulf of Alaska earthquake ruptured an oceanic fracture zone
      system offshore Kodiak Island. Bathymetric compilations show a muted topographic
      expression of the fracture zone due to the thick sediment that covers oceanic
      basement but the fracture zone system can be identified by offset N-S magnetic
      anomalies and E-W linear zones in the vertical gravity gradient. Back-projection
      from global seismic stations reveals that the initial rupture at first propagated
      from the epicenter to the north, likely rupturing along a weak zone parallel to
      the ocean crustal fabric. The rupture then changed direction to eastward directed
      with most energy emitted on Aka fracture zone resulting in an unusual multi-fault
      earthquake. Similarly, the aftershocks show complex behavior and are related to
      two different tectonic structures: (1) events along N-S trending oceanic fabric,
      which ruptured mainly strike-slip and additionally, in normal and oblique slip
      mechanisms and (2) strike-slip events along E-W oriented fracture zones. To
      explain the complex faulting behavior we adopt the classical stress and strain
      partitioning concept and propose a generalized model for large intra-oceanic
      strike-slip earthquakes of trench-oblique oriented fracture zones/ocean plate
      fabric near subduction zones. Taking the Kodiak asperity position of 1964 maximum
      afterslip and outer-rise Coulomb stress distribution into account, we propose
      that the unusual 2018 Gulf of Alaska moment release was stress transferred to the
      incoming oceanic plate from co- and post-processes of the nearby great 1964 MW
      9.2 megathrust earthquake.

PMID- 30209261
TI  - Affective computing in virtual reality: emotion recognition from brain and
      heartbeat dynamics using wearable sensors.
AB  - Affective Computing has emerged as an important field of study that aims to
      develop systems that can automatically recognize emotions. Up to the present,
      elicitation has been carried out with non-immersive stimuli. This study, on the
      other hand, aims to develop an emotion recognition system for affective states
      evoked through Immersive Virtual Environments. Four alternative virtual rooms
      were designed to elicit four possible arousal-valence combinations, as described
      in each quadrant of the Circumplex Model of Affects. An experiment involving the
      recording of the electroencephalography (EEG) and electrocardiography (ECG) of
      sixty participants was carried out. A set of features was extracted from these
      signals using various state-of-the-art metrics that quantify brain and
      cardiovascular linear and nonlinear dynamics, which were input into a Support
      Vector Machine classifier to predict the subject's arousal and valence
      perception. The model's accuracy was 75.00% along the arousal dimension and
      71.21% along the valence dimension. Our findings validate the use of Immersive
      Virtual Environments to elicit and automatically recognize different emotional
      states from neural and cardiac dynamics; this development could have novel
      applications in fields as diverse as Architecture, Health, Education and
      Videogames.

PMID- 30209263
TI  - Both trait-neutrality and filtering effects are validated by the vegetation
      patterns detected in the functional recovery of sand grasslands.
AB  - Neutral theory of species assembly means that species assembly is governed by
      stochastic dispersal processes and fluctuations in established populations. An
      alternative theory suggests that assembly is strongly determined by functional
      trait filtering governed by abiotic and biotic filtering selecting species from
      the local species pool. To test these assumptions, in the current paper we
      analysed vegetation changes in the first 12 years of succession after heavy goose
      grazing on acidic sand. With trait-based analyses using permanent plots we
      addressed the following hypotheses: (i) High fluctuations in the trait values are
      typical in the first years; later a temporally divergent change in the trait
      patterns of sites with different vertical position became characteristic. (ii) In
      the functional diversity of regenerative and vegetative traits we expected
      different temporal patterns. We confirmed the first hypothesis, as in the first
      few years most traits displayed high fluctuations with no clear patterns. Our
      findings weakly supported the second hypothesis; while there were distinct
      patterns detected in the functional richness of traits, functional divergence and
      evenness displayed no clear distinctive patterns. We can conclude that both trait
      neutrality and filtering effects operate in the vegetation changes of the first
      period of secondary succession.

PMID- 30209266
TI  - A new knotless technique for combined transscleral fixation of artificial iris,
      posterior chamber intraocular lens, and penetrating keratoplasty.
AB  - PURPOSE: To present a new surgical technique for treating corneal opacity and
      aniridia with aphakia and the results in a small consecutive case series.
      METHODS: A three-piece acrylic intraocular lens (IOL) was attached to a
      customized silicone iris prosthesis and fixed with three 10-0 polypropylene
      sutures in a knotless technique using Z-sutures after trephination of the
      recipient cornea. The medical records of all consecutive patients who had
      received a keratoplasty and an implantation of an artificial iris and IOL were
      reviewed. RESULTS: Five eyes of five patients were included in the analysis. The
      mean age of the patients was 46.2 years and the mean follow-up was 24.6 months.
      The mean best-corrected visual acuity improved from 1.36 logMAR before surgery to
      0.78 logMAR after surgery during the follow-up. At the last follow-up visit, the
      artificial iris-IOL complex was well centered with good positioning in all cases.
      CONCLUSIONS: Management of post-traumatic aniridia combined with aphakia and
      corneal scars or graft failure by haptic fixation of a foldable IOL on an
      artificial iris combined with a simultaneous keratoplasty appears to be a
      promising approach, which allows to correct a complex lesion with a less
      traumatic and faster procedure.

PMID- 30209265
TI  - Glucose-regulated protein 78 binds to and regulates the melanocortin-4 receptor.
AB  - The melanocortin-4 receptor (MC4R) belongs to the G protein-coupled receptor
      (GPCR) family and plays an essential role in the control of energy homeostasis.
      Here, we identified a novel MC4R-interacting protein, glucose-regulated protein
      78 (GRP78), from a pulldown assay using hypothalamic protein extracts and the
      third intracellular loop of MC4R. We found that MC4R interacted with GRP78 in
      both the cytosol and at the cell surface and that this interaction increased when
      MC4R was internalized in the presence of the agonist melanotan-II (MTII).
      Downregulation of GRP78 using a short interfering RNA approach attenuated MTII
      mediated receptor internalization. Reduction in GRP78 expression during
      tunicamycin-induced endoplasmic reticulum stress also suppressed MTII-mediated
      internalization of MC4R and cAMP-mediated transcriptional activity. Furthermore,
      lentiviral-mediated short hairpin RNA knockdown of endogenous GRP78 in the
      paraventricular nucleus (PVN) of the hypothalamus resulted in an increase in body
      weight in mice fed a high-fat diet. These results suggest that GRP78 in the PVN
      binds to MC4R and may have a chaperone-like role in the regulation of MC4R
      trafficking and signaling.

PMID- 30209267
TI  - Simultaneous assessment of aberrant retinal vascularization, thickness, and
      function in an in vivo mouse oxygen-induced retinopathy model.
AB  - BACKGROUND: Retinopathy of prematurity is a condition of abnormal retinal
      vascularization in premature infants. The effect of abnormal vascularization on
      retinal structure and function is unclear. In vivo studies of retinal
      vascularization, thickness, and function were performed in mice with oxygen
      induced retinopathy (OIR mice). METHODS: Eighteen mice were exposed to hyperoxia
      at postnatal day (P) 7, whereas 18 mice were raised in room air (RA). At P20 and
      40, electroretinogram was performed for a-wave and b-wave amplitudes and peak
      times, followed by simultaneous fluorescein angiography for retinal avascular
      area, arterial tortuosity, and vein dilation assessments, and spectral domain
      optical coherence tomography for retinal thickness. RESULTS: Capillary density
      appeared sparser in OIR mice, but retinal avascular area similar to RA mice.
      Retinal artery tortuosity was higher at P20 and P40 (P = 0.0001) in OIR than RA
      mice. OIR mice had dilated retinal veins at P20 and thinner inner retinas at P40.
      Retinal vein width positively correlated with inner retinal thickness (P =
      0.008). b-wave amplitude was decreased in avascular retinal areas, and correlated
      with inner retinal thinning. b-wave peak time was prolonged in adult OIR mice at
      high intensities (P = 0.03). CONCLUSIONS: Focal variations in retinal
      vascularization of OIR mice correlate with thickness and function. Adult OIR mice
      had increased retinal artery tortuosity, prolonged b-wave peak time, and
      decreased retinal vein width with inner retina attrition. These suggest
      abnormalities in inner retinal morphology or post-receptor signaling. Studying
      interactions between retinal vascular, structural, and functional changes could
      enhance knowledge of OIR pathogenesis and potential therapies.

PMID- 30209264
TI  - Factors of the bone marrow microniche that support human plasma cell survival and
      immunoglobulin secretion.
AB  - Human antibody-secreting cells (ASC) in peripheral blood are found after
      vaccination or infection but rapidly apoptose unless they migrate to the bone
      marrow (BM). Yet, elements of the BM microenvironment required to sustain long
      lived plasma cells (LLPC) remain elusive. Here, we identify BM factors that
      maintain human ASC > 50 days in vitro. The critical components of the cell-free
      in vitro BM mimic consist of products from primary BM mesenchymal stromal cells
      (MSC), a proliferation-inducing ligand (APRIL), and hypoxic conditions.
      Comparative analysis of protein-protein interactions between BM-MSC proteomics
      with differential RNA transcriptomics of blood ASC and BM LLPC identify two major
      survival factors, fibronectin and YWHAZ. The MSC secretome proteins and hypoxic
      conditions play a role in LLPC survival utilizing mechanisms that downregulate
      mTORC1 signaling and upregulate hypoxia signatures. In summary, we identify
      elements of the BM survival niche critical for maturation of blood ASC to BM
      LLPC.

PMID- 30209268
TI  - Speed dependent descending control of freezing behavior in Drosophila
      melanogaster.
AB  - The most fundamental choice an animal has to make when it detects a threat is
      whether to freeze, reducing its chances of being noticed, or to flee to safety.
      Here we show that Drosophila melanogaster exposed to looming stimuli in a
      confined arena either freeze or flee. The probability of freezing versus fleeing
      is modulated by the fly's walking speed at the time of threat, demonstrating that
      freeze/flee decisions depend on behavioral state. We describe a pair of
      descending neurons crucially implicated in freezing. Genetic silencing of DNp09
      descending neurons disrupts freezing yet does not prevent fleeing. Optogenetic
      activation of both DNp09 neurons induces running and freezing in a state
      dependent manner. Our findings establish walking speed as a key factor in
      defensive response choices and reveal a pair of descending neurons as a critical
      component in the circuitry mediating selection and execution of freezing or
      fleeing behaviors.

PMID- 30209269
TI  - Genomic characterization and infectivity of a novel SARS-like coronavirus in
      Chinese bats.
AB  - SARS coronavirus (SARS-CoV), the causative agent of the large SARS outbreak in
      2003, originated in bats. Many SARS-like coronaviruses (SL-CoVs) have been
      detected in bats, particularly those that reside in China, Europe, and Africa. To
      further understand the evolutionary relationship between SARS-CoV and its
      reservoirs, 334 bats were collected from Zhoushan city, Zhejiang province, China,
      between 2015 and 2017. PCR amplification of the conserved coronaviral protein
      RdRp detected coronaviruses in 26.65% of bats belonging to this region, and this
      number was influenced by seasonal changes. Full genomic analyses of the two new
      SL-CoVs from Zhoushan (ZXC21 and ZC45) showed that their genomes were 29,732
      nucleotides (nt) and 29,802 nt in length, respectively, with 13 open reading
      frames (ORFs). These results revealed 81% shared nucleotide identity with
      human/civet SARS CoVs, which was more distant than that observed previously for
      bat SL-CoVs in China. Importantly, using pathogenic tests, we found that the
      virus can reproduce and cause disease in suckling rats, and further studies
      showed that the virus-like particles can be observed in the brains of suckling
      rats by electron microscopy. Thus, this study increased our understanding of the
      genetic diversity of the SL-CoVs carried by bats and also provided a new
      perspective to study the possibility of cross-species transmission of SL-CoVs
      using suckling rats as an animal model.

PMID- 30209270
TI  - Superconducting metamaterials for waveguide quantum electrodynamics.
AB  - Embedding tunable quantum emitters in a photonic bandgap structure enables
      control of dissipative and dispersive interactions between emitters and their
      photonic bath. Operation in the transmission band, outside the gap, allows for
      studying waveguide quantum electrodynamics in the slow-light regime.
      Alternatively, tuning the emitter into the bandgap results in finite-range
      emitter-emitter interactions via bound photonic states. Here, we couple a
      transmon qubit to a superconducting metamaterial with a deep sub-wavelength
      lattice constant (lambda/60). The metamaterial is formed by periodically loading
      a transmission line with compact, low-loss, low-disorder lumped-element microwave
      resonators. Tuning the qubit frequency in the vicinity of a band-edge with a
      group index of ng = 450, we observe an anomalous Lamb shift of -28 MHz
      accompanied by a 24-fold enhancement in the qubit lifetime. In addition, we
      demonstrate selective enhancement and inhibition of spontaneous emission of
      different transmon transitions, which provide simultaneous access to short-lived
      radiatively damped and long-lived metastable qubit states.

PMID- 30209273
TI  - Combining newborn metabolic and DNA analysis for second-tier testing of
      methylmalonic acidemia.
AB  - PURPOSE: Improved second-tier tools are needed to reduce false-positive outcomes
      in newborn screening (NBS) for inborn metabolic disorders on the Recommended
      Universal Screening Panel (RUSP). METHODS: We designed an assay for multiplex
      sequencing of 72 metabolic genes (RUSPseq) from newborn dried blood spots.
      Analytical and clinical performance was evaluated in 60 screen-positive newborns
      for methylmalonic acidemia (MMA) reported by the California Department of Public
      Health NBS program. Additionally, we trained a Random Forest machine learning
      classifier on NBS data to improve prediction of true and false-positive MMA
      cases. RESULTS: Of 28 MMA patients sequenced, we found two pathogenic or likely
      pathogenic (P/LP) variants in a MMA-related gene in 24 patients, and one
      pathogenic variant and a variant of unknown significance (VUS) in 1 patient. No
      such variant combinations were detected in MMA false positives and healthy
      controls. Random Forest-based analysis of the entire NBS metabolic profile
      correctly identified the MMA patients and reduced MMA false-positive cases by
      51%. MMA screen-positive newborns were more likely of Hispanic ethnicity.
      CONCLUSION: Our two-pronged approach reduced false positives by half and provided
      a reportable molecular finding for 89% of MMA patients. Challenges remain in
      newborn metabolic screening and DNA variant interpretation in diverse multiethnic
      populations.

PMID- 30209272
TI  - Correction: Effectiveness of plasma lyso-Gb3 as a biomarker for selecting high
      risk patients with Fabry disease from multispecialty clinics for genetic
      analysis.
AB  - The PDF and HTML versions of the article have been updated to include the
      Creative Commons Attribution 4.0 International License information.

PMID- 30209271
TI  - Parental interest in genomic sequencing of newborns: enrollment experience from
      the BabySeq Project.
AB  - PURPOSE: Newborn genomic sequencing (nGS) has great potential to improve
      pediatric care. Parental interest and concerns about genomics are relatively
      unexplored. Understanding why parents decline research consent for nGS may reveal
      implementation barriers. METHODS: We evaluated parental interest in a randomized
      trial of nGS in well-baby and intensive care unit nursery settings. Interested
      families attended an informational enrollment session (ES) with a genetic
      counselor prior to consenting. Reason(s) for declining participation and
      sociodemographic associations were analyzed. RESULTS: Of 3860 eligible approached
      families, 10% attended ES, 67% of whom enrolled. Of 1760 families queried for
      decline reasons, 58% were uninterested in research. Among 499 families
      considering research, principal reasons for decline prior to ES included
      burdensome study logistics (48%), feeling overwhelmed postpartum (17%), and lack
      of interest/discomfort with genetic testing (17%). Decliners after ES more often
      cited concerns about privacy/insurability (41%) and uncertain/unfavorable results
      (23%). CONCLUSION: Low interest in research and study logistics were major
      initial barriers to postpartum enrollment and are likely generic to many
      postpartum research efforts. Concerns over privacy and result implications were
      most commonly cited in decliners after ES. Understanding parental concerns around
      research nGS may inform future integration of nGS into newborn screening,
      predictive testing, and pediatric diagnostics.

PMID- 30209274
TI  - Prospective motor control obeys to idiosyncratic strategies in autism.
AB  - Disturbance of primary prospective motor control has been proposed to contribute
      to faults in higher mind functions of individuals with autism spectrum disorder,
      but little research has been conducted to characterize prospective control
      strategies in autism. In the current study, we applied pattern-classification
      analyses to kinematic features to verify whether children with autism spectrum
      disorder (ASD) and typically developing (TD) children altered their initial grasp
      in anticipation of self- and other-actions. Results indicate that children with
      autism adjusted their behavior to accommodate onward actions. The way they did
      so, however, varied idiosyncratically from one individual to another, which
      suggests that previous characterizations of general lack of prospective control
      strategies may be overly simplistic. These findings link abnormalities in
      anticipatory control with increased variability and offer insights into the
      difficulties that individuals with ASD may experience in social interaction.

PMID- 30209276
TI  - Singlet oxygen imaging using fluorescent probe Singlet Oxygen Sensor Green in
      photosynthetic organisms.
AB  - Formation of singlet oxygen (1O2) was reported to accompany light stress in
      plants, contributing to cell signaling or oxidative damage. So far, Singlet
      Oxygen Sensor Green (SOSG) has been the only commercialized fluorescent probe for
      1O2 imaging though it suffers from several limitations (unequal penetration and
      photosensitization) that need to be carefully considered to avoid
      misinterpretation of the analysed data. Herein, we present results of a
      comprehensive study focused on the appropriateness of SOSG for 1O2 imaging in
      three model photosynthetic organisms, unicellular cyanobacteria Synechocystis sp.
      PCC 6803, unicellular green alga Chlamydomonas reinhardtii and higher plant
      Arabidopsis thaliana. Penetration of SOSG differs in both unicellular organisms;
      while it is rather convenient for Chlamydomonas it is restricted by the presence
      of mucoid sheath of Synechocystis, which penetrability might be improved by mild
      heating. In Arabidopsis, SOSG penetration is limited due to tissue complexity
      which can be increased by pressure infiltration using a shut syringe.
      Photosensitization of SOSG and SOSG endoperoxide formed by its interaction with
      1O2 might be prevented by illumination of samples by a red light. When measured
      under controlled conditions given above, SOSG might serve as specific probe for
      detection of intracellular 1O2 formation in photosynthetic organisms.

PMID- 30209277
TI  - Implantable Photothermal Agents based on Gold Nanorods-Encapsulated Microcube.
AB  - Gold nanorods (GNRs) are of great interest in cancer therapy given their ability
      to ablate tumor cells using deep tissue-penetrating near-infrared light. GNRs
      coated with tumor-specific moieties have the potential to target tumor tissue to
      minimize damage to normal tissue. However, perfect targeting is difficult to
      achieve given that nanoparticles could be broadly dispersed inside the body.
      Moreover, interaction between targeting groups and biological molecules could
      lower targeting abilities, resulting in off-target accumulation which might
      produce nanotoxicity. Here we introduce GNR-encapsulated microcubes (GNR@MCs)
      that can be utilized as implantable photothermal agents. GNR@MCs are created by
      encapsulating GNRs in polymeric networks via stop flow lithography (SFL), a one
      phase synthesis technique which allows for creation of surfactant-free, uniform
      particles, and injection of GNR@MCs into the body after a simple rinse step. GNRs
      are highly packed and firmly encapsulated inside MCs, and entrapped GNRs exhibit
      optical properties comparable to that of unbound GNRs and photothermal efficiency
      (58%) in line with that of nano-sized agents (51-95%). Photothermal ablation in
      murine models is achieved using GNR@MCs stably implanted into the tumor tissue,
      which suggests that GNR@MCs can be a safe and effective platform for cancer
      therapy.

PMID- 30209278
TI  - Seismic imaging and petrology explain highly explosive eruptions of Merapi
      Volcano, Indonesia.
AB  - Our seismic tomographic images characterize, for the first time, spatial and
      volumetric details of the subvertical magma plumbing system of Merapi Volcano. We
      present P- and S-wave arrival time data, which were collected in a dense seismic
      network, known as DOMERAPI, installed around the volcano for 18 months. The P-
      and S-wave arrival time data with similar path coverage reveal a high Vp/Vs
      structure extending from a depth of >=20 km below mean sea level (MSL) up to the
      summit of the volcano. Combined with results of petrological studies, our seismic
      tomography data allow us to propose: (1) the existence of a shallow zone of
      intense fluid percolation, directly below the summit of the volcano; (2) a main,
      pre-eruptive magma reservoir at >= 10 to 20 km below MSL that is orders of
      magnitude larger than erupted magma volumes; (3) a deep magma reservoir at MOHO
      depth which supplies the main reservoir; and (4) an extensive, subvertical fluid
      magma-transfer zone from the mantle to the surface. Such high-resolution spatial
      constraints on the volcano plumbing system as shown are an important advance in
      our ability to forecast and to mitigate the hazard potential of Merapi's future
      eruptions.

PMID- 30209275
TI  - Birth weight and catch up growth are associated with childhood impulsivity in two
      independent cohorts.
AB  - Individuals born after intrauterine growth restriction (IUGR) are more impulsive
      towards palatable foods, but it is not clear 1) if IUGR-related impulsivity is
      specific for foods and solely based on response inhibition and 2) if the
      development of impulsivity is due to being born IUGR per se or to growing up fast
      in the first few years of life (catch up growth). Children were classified in the
      IUGR group if the birth weight ratio was below 0.85. Delta z score for BMI was
      used as a measure of catch up growth. In MAVAN (N = 274), impulsivity was
      measured by the Information Sampling Task from the Cambridge Neuropsychological
      Test Automated Battery (IST - CANTAB), and in GUSTO using the Sticker Delay Task
      (N = 327). There is a significant effect of interaction between being born IUGR
      and the magnitude of catch up growth on the reflection impulsivity from IST
      CANTAB at 60 months, in which greater catch up growth associates with greater
      impulsivity in the IST fixed condition in IUGR children. The finding was
      reproduced in children from the GUSTO cohort using the Sticker Delay Task. We
      confirmed that catch up growth interacts with IUGR, having a major role in the
      development of impulsivity in the first years of life and influencing inhibitory
      control and decision making processes.

PMID- 30209279
TI  - A comparison of the effectiveness of cyclophosphamide, leflunomide,
      corticosteroids, or conservative management alone in patients with IgA
      nephropathy: a retrospective observational study.
AB  - To compare the long-term efficacy of corticosteroids (P) alone or in combination
      with cyclophosphamide (CTX), leflunomide (LEF), or Angiotensin-convertase
      inhibitors or angiotensin II receptor blockers (ACEI/ARB) in treatment for IgA
      nephropathy (IgAN), 311 patients with IgAN were identified. Therapeutic
      effectiveness (including progression, partial remission, complete remission) and
      combined renal endpoint (defined as 30% reduction in eGFR or ESRD) were compared
      based on different therapies. After immunosuppressive and ACEI/ARB treatment, the
      levels of eGFR, proteinuria and albumin were significantly improved at the last
      follow-up, the extent of improvement of eGFR, proteinuria, and albumin was more
      notable in P + CTX group and P + LEF group. 41%, 52.2%, 55.3% and 55.2% in P +
      CTX, P + LEF, P and ACEI/ARB group achieved complete remission, respectively.
      Multivariate regression analysis indicated that only proteinuria (Relative risk
      (RR) 0.82(0.72-0.94), P = 0.004) and tubular atrophy/interstitial fibrosis (RR
      0.26(0.13-0.57), P = 0.001) were predictors for complete remission. The optimal
      cutoffs of eGFR was 47.085 ml/min/1.73 m2 predicting renal function recovery in P
      + CTX therapy. In conclusion, tubular atrophy/interstitial fibrosis and massive
      proteinuria were poor predictors for complete remission in IgAN, it appears as
      though patients may have benefited from immunosuppressive treatment but that
      comparison to a well-matched contemporary control group or, ideally, a randomized
      controlled clinical trial, would be required to show this.

PMID- 30209280
TI  - Prenatal testosterone does not explain sex differences in spatial ability.
AB  - The most consistent sex differences in cognition are found for spatial ability,
      in which males, on average, outperform females. Utilizing a twin design, two
      studies have shown that females with male co-twins perform better than females
      with female co-twins on a mental rotation task. According to the Twin
      Testosterone Transfer hypothesis (TTT) this advantage is due to in-uterine
      transmission of testosterone from males to females. The present study tested the
      TTT across 14 different spatial ability measures, including mental rotation
      tasks, in a large sample of 19-21-year-old twins. Males performed significantly
      better than females on all spatial tasks, with effect sizes ranging from eta2 =
      0.02 to eta2 = 0.16. Females with a male co-twin outperformed females with a
      female co-twin in two of the tasks. The effect sizes for both differences were
      negligible (eta2 < 0.02). Contrary to the previous studies, our results gave no
      indication that prenatally transferred testosterone, from a male to a female
      twin, influences sex differences in spatial ability.

PMID- 30209282
TI  - PDE3A gene screening improves diagnostics for patients with Bilginturan syndrome
      (hypertension and brachydactyly syndrome).
AB  - Autosomal-dominant hypertension and brachydactyly syndrome (HTNB; Bilginturan
      syndrome) is known to cause stroke before age 50 when untreated. We report a
      novel PDE3A gene mutation in a mother and daughter affected with dominant
      brachydactyly of the hands and feet, a short stature, and hypertension. The
      hypertension was medically responsive to anti-hypertensive treatment. The 3-bp
      deletion in the PDE3A gene presented de novo in the mother. Here, we expand the
      list of PDE3A mutations identified in Bilginturan syndrome and emphasize the
      importance of standardized genetic testing of HTNB patients to improve
      diagnostics at an early age. We recommend extended phenotyping in patients with
      brachydactyly, a short stature or hypertension in clinical practice.

PMID- 30209283
TI  - Azilsartan attenuates cardiac damage caused by high salt intake through the
      downregulation of the cardiac (pro)renin receptor and its downstream signals in
      spontaneously hypertensive rats.
AB  - We examined whether the stimulation of the angiotensin II AT1 receptor increases
      the expression of the cardiac (pro)renin receptor ((P)RR) and its downstream
      signals and whether the blockade of the angiotensin II AT1 receptor by azilsartan
      decreases the expression of the cardiac (P)RR and its signaling in spontaneously
      hypertensive rats (SHRs) with a high-salt intake. Rats received normal-salt
      (0.9%) chow, high-salt (8.9%) chow, normal-salt chow with 1 mg/day of azilsartan,
      and high-salt chow with 1 mg/day of azilsartan from 6 to 12 weeks of age. Rats
      with normal-salt chow were administered 100 ng/kg/min of angiotensin II by
      osmotic minipump from 6 to 12 weeks of age. A high-salt diet and angiotensin II
      significantly increased the systolic blood pressure; overexpressed cardiac (P)RR,
      phosphorylated (p)-ERK1/2, p-p38MAPK, p-HSP27, and TGF-beta1; enhanced cardiac
      interstitial and perivascular fibrosis, cardiomyocyte size, interventricular
      septum (IVS) thickness, and left ventricular (LV) end-diastolic dimension; and
      decreased LV fractional shortening. Azilsartan decreased systolic blood pressure,
      cardiac expressions of (P)RR, p-ERK1/2, p-p38MAPK, p-HSP27, and TGF-beta1,
      cardiac interstitial and perivascular fibrosis, cardiomyocyte size, and LV
      diastolic dimension, and improved LV fractional shortening. In conclusion,
      azilsartan attenuates cardiac damage caused by high salt intake through the
      downregulation of the cardiac (pro)renin receptor and its downstream signals in
      SHRs.

PMID- 30209281
TI  - 3D Shape Modeling for Cell Nuclear Morphological Analysis and Classification.
AB  - Quantitative analysis of morphological changes in a cell nucleus is important for
      the understanding of nuclear architecture and its relationship with pathological
      conditions such as cancer. However, dimensionality of imaging data, together with
      a great variability of nuclear shapes, presents challenges for 3D morphological
      analysis. Thus, there is a compelling need for robust 3D nuclear morphometric
      techniques to carry out population-wide analysis. We propose a new approach that
      combines modeling, analysis, and interpretation of morphometric characteristics
      of cell nuclei and nucleoli in 3D. We used robust surface reconstruction that
      allows accurate approximation of 3D object boundary. Then, we computed geometric
      morphological measures characterizing the form of cell nuclei and nucleoli. Using
      these features, we compared over 450 nuclei with about 1,000 nucleoli of
      epithelial and mesenchymal prostate cancer cells, as well as 1,000 nuclei with
      over 2,000 nucleoli from serum-starved and proliferating fibroblast cells.
      Classification of sets of 9 and 15 cells achieved accuracy of 95.4% and 98%,
      respectively, for prostate cancer cells, and 95% and 98% for fibroblast cells. To
      our knowledge, this is the first attempt to combine these methods for 3D nuclear
      shape modeling and morphometry into a highly parallel pipeline workflow for
      morphometric analysis of thousands of nuclei and nucleoli in 3D.

PMID- 30209284
TI  - Urinary sodium-to-potassium ratio and serum asymmetric dimethylarginine levels in
      patients with type 2 diabetes.
AB  - Obesity modifies the association between sodium and potassium intake and blood
      pressure. However, the impact of obesity on the relationship between the sodium
      potassium balance and cardiovascular risk in type 2 diabetes (T2DM) patients
      remains unclear. We investigated the relationship between the 24-h urinary sodium
      to-potassium ratio and serum asymmetric dimethylarginine (ADMA) level, which is a
      cardiovascular risk factor, in Japanese T2D patients with or without obesity.
      This cross-sectional study included 243 patients with T2DM who were hospitalized
      for diabetes education. Urinary sodium-to-potassium ratios were calculated from
      24-h urine collection. The subjects were divided into two groups according to
      their BMIs (<25 and >=25). The serum ADMA levels positively correlated with the
      urinary sodium-to-potassium ratios in non-obese patients, but not in obese
      patients. Multivariate linear regression analyses showed that the serum ADMA
      levels positively correlated with the urinary sodium-to-potassium ratios after
      adjustment for other confounders in non-obese patients. This correlation was
      observed in non-obese patients with hypertension, but not in those without
      hypertension. Measurement of the pulse wave velocity and intima-media thickness
      revealed that elevation of the serum ADMA levels was significantly associated
      with an increase in the degree of atherosclerotic progression in subjects with
      T2DM. Additionally, an assessment of dietary intake showed that the consumption
      of dairy products as well as of green and yellow vegetables was negatively
      associated with urinary sodium-to-potassium ratios in patients with T2DM. In
      conclusion, elevation of serum ADMA may be positively associated with the urinary
      sodium-to-potassium ratio in Japanese non-obese patients with T2DM.

PMID- 30209285
TI  - Characterization and targeting of malignant stem cells in patients with advanced
      myelodysplastic syndromes.
AB  - Myelodysplastic syndrome (MDS) is a chronic hematologic disorder that frequently
      evolves to more aggressive stages and in some cases leads to acute myeloid
      leukemia (AML). MDS arises from mutations in hematopoietic stem cells (HSCs).
      Thus, to define optimal therapies, it is essential to understand molecular events
      driving HSC pathogenesis. In this study, we report that during evolution of MDS,
      malignant HSCs activate distinct cellular programs that render such cells
      susceptible to therapeutic intervention. Specifically, metabolic analyses of the
      MDS stem cell compartment show a profound activation of protein synthesis
      machinery and increased oxidative phosphorylation. Pharmacological targeting of
      protein synthesis and oxidative phosphorylation demonstrated potent and selective
      eradication of MDS stem cells in primary human patient specimens. Taken together,
      our findings indicate that MDS stem cells are reliant on specific metabolic
      events and that such properties can be targeted prior to the onset of clinically
      significant AML, during antecedent MDS.

PMID- 30209286
TI  - Brain and psychological determinants of placebo pill response in chronic pain
      patients.
AB  - The placebo response is universally observed in clinical trials of pain
      treatments, yet the individual characteristics rendering a patient a 'placebo
      responder' remain unclear. Here, in chronic back pain patients, we demonstrate
      using MRI and fMRI that the response to placebo 'analgesic' pills depends on
      brain structure and function. Subcortical limbic volume asymmetry, sensorimotor
      cortical thickness, and functional coupling of prefrontal regions, anterior
      cingulate, and periaqueductal gray were predictive of response. These neural
      traits were present before exposure to the pill and most remained stable across
      treatment and washout periods. Further, psychological traits, including
      interoceptive awareness and openness, were also predictive of the magnitude of
      response. These results shed light on psychological, neuroanatomical, and
      neurophysiological principles determining placebo response in RCTs in chronic
      pain patients, and they suggest that the long-term beneficial effects of placebo,
      as observed in clinical settings, are partially predictable.

PMID- 30209288
TI  - "Green" Aqueous Synthesis and Advanced Spectral Characterization of Size-Selected
      Cu2ZnSnS4 Nanocrystal Inks.
AB  - Structure, composition, and optical properties of colloidal mercaptoacetate
      stabilized Cu2ZnSnS4 (CZTS) nanocrystal inks produced by a "green" method
      directly in aqueous solutions were characterized. A size-selective precipitation
      procedure using 2-propanol as a non-solvent allows separating a series of
      fractions of CZTS nanocrystals with an average size (bandgap) varying from 3 nm
      (1.72 eV) to 2 nm (2.04 eV). The size-selected CZTS nanocrystals revealed also
      phonon confinement, with the main phonon mode frequency varying by about 4 cm-1
      between 2 nm and 3 nm NCs.

PMID- 30209287
TI  - First evidence of octacalcium phosphate@osteocalcin nanocomplex as skeletal bone
      component directing collagen triple-helix nanofibril mineralization.
AB  - Tibia trabeculae and vertebrae of rats as well as human femur were investigated
      by high-resolution TEM at the atomic scale in order to reveal snapshots of the
      morphogenetic processes of local bone ultrastructure formation. By taking into
      account reflections of hydroxyapatite for Fourier filtering the appearance of
      individual alpha-chains within the triple-helix clearly shows that bone bears the
      feature of an intergrowth composite structure extending from the atomic to the
      nanoscale, thus representing a molecular composite of collagen and apatite.
      Careful Fourier analysis reveals that the non-collagenous protein osteocalcin is
      present directly combined with octacalcium phosphate. Besides single spherical
      specimen of about 2 nm in diameter, osteocalcin is spread between and over
      collagen fibrils and is often observed as pearl necklace strings. In high
      resolution TEM, the three binding sites of the gamma-carboxylated glutamic acid
      groups of the mineralized osteocalcin were successfully imaged, which provide the
      chemical binding to octacalcium phosphate. Osteocalcin is attached to the
      collagen structure and interacts with the Ca-sites on the (100) dominated
      hydroxyapatite platelets with Ca-Ca distances of about 9.5 A. Thus, osteocalcin
      takes on the functions of Ca-ion transport and suppression of hydroxyapatite
      expansion.

PMID- 30209289
TI  - Monolayer-graphene-based broadband and wide-angle perfect absorption structures
      in the near infrared.
AB  - Broadband optical absorption structures in the near infrared by coupling
      monolayer-graphene with periodical metal structures are proposed and demonstrated
      numerically. Optical absorption of graphene with over-50%-absorption bandwidth up
      to hundreds of nanometer caused by magnetic dipole resonances and magnetic
      coupling effect are investigated in detail, and the demonstrated bandwidths are
      one order higher than those caused by dielectric guiding mode resonances. In
      addition, the influences of geometrical parameters of structures are fully
      analyzed and these demonstrated structures show angular-insensitive absorption
      for oblique incidence in a large angular range. The demonstrated absorption
      structures in this work provide new design ideas in the realization of advanced
      graphene-based optoelectronic devices.

PMID- 30209290
TI  - A microfluidic device for isolating intact chromosomes from single mammalian
      cells and probing their folding stability by controlling solution conditions.
AB  - Chromatin folding shows spatio-temporal fluctuations in living undifferentiated
      cells, but fixed spatial heterogeneity in differentiated cells. However, little
      is known about variation in folding stability along the chromatin fibres during
      differentiation. In addition, effective methods to investigate folding stability
      at the single cell level are lacking. In the present study, we developed a
      microfluidic device that enables non-destructive isolation of chromosomes from
      single mammalian cells as well as real-time microscopic monitoring of the partial
      unfolding and stretching of individual chromosomes with increasing salt
      concentrations under a gentle flow. Using this device, we compared the folding
      stability of chromosomes between non-differentiated and differentiated cells and
      found that the salt concentration which induces the chromosome unfolding was
      lower (<=500 mM NaCl) for chromosomes derived from undifferentiated cells,
      suggesting that the chromatin folding stability of these cells is lower than that
      of differentiated cells. In addition, individual unfolded chromosomes, i.e.,
      chromatin fibres, were stretched to 150-800 um non-destructively under 750 mM
      NaCl and showed distributions of highly/less folded regions along the fibres.
      Thus, our technique can provide insights into the aspects of chromatin folding
      that influence the epigenetic control of cell differentiation.

PMID- 30209291
TI  - Genomic comparisons reveal biogeographic and anthropogenic impacts in the koala
      (Phascolarctos cinereus): a dietary-specialist species distributed across
      heterogeneous environments.
AB  - The Australian koala is an iconic marsupial with highly specific dietary
      requirements distributed across heterogeneous environments, over a large
      geographic range. The distribution and genetic structure of koala populations has
      been heavily influenced by human actions, specifically habitat modification,
      hunting and translocation of koalas. There is currently limited information on
      population diversity and gene flow at a species-wide scale, or with consideration
      to the potential impacts of local adaptation. Using species-wide sampling across
      heterogeneous environments, and high-density genome-wide markers (SNPs and PAVs),
      we show that most koala populations display levels of diversity comparable to
      other outbred species, except for those populations impacted by population
      reductions. Genetic clustering analysis and phylogenetic reconstruction reveals a
      lack of support for current taxonomic classification of three koala subspecies,
      with only a single evolutionary significant unit supported. Furthermore, ~70% of
      genetic variance is accounted for at the individual level. The Sydney Basin
      region is highlighted as a unique reservoir of genetic diversity, having higher
      diversity levels (i.e., Blue Mountains region; AvHecorr=0.20, PL% = 68.6). Broad
      scale population differentiation is primarily driven by an isolation by distance
      genetic structure model (49% of genetic variance), with clinal local adaptation
      corresponding to habitat bioregions. Signatures of selection were detected
      between bioregions, with no single region returning evidence of strong selection.
      The results of this study show that although the koala is widely considered to be
      a dietary-specialist species, this apparent specialisation has not limited the
      koala's ability to maintain gene flow and adapt across divergent environments as
      long as the required food source is available.

PMID- 30209292
TI  - Epistasis regulates the developmental stability of the mouse craniofacial shape.
AB  - Fluctuating asymmetry is a classic concept linked to organismal development. It
      has traditionally been used as a measure of developmental instability, which is
      the inability of an organism to buffer environmental fluctuations during
      development. Developmental stability has a genetic component that influences the
      final phenotype of the organism and can lead to congenital disorders. According
      to alternative hypotheses, this genetic component might be either the result of
      additive genetic effects or a by-product of developmental gene networks. Here we
      present a genome-wide association study of the genetic architecture of
      fluctuating asymmetry of the skull shape in mice. Geometric morphometric methods
      were applied to quantify fluctuating asymmetry: we estimated fluctuating
      asymmetry as Mahalanobis distances to the mean asymmetry, correcting first for
      genetic directional asymmetry. We applied the marginal epistasis test to study
      epistasis among genomic regions. Results showed no evidence of additive effects
      but several interacting regions significantly associated with fluctuating
      asymmetry. Among the candidate genes overlapping these interacting regions we
      found an over-representation of genes involved in craniofacial development. A
      gene network is likely to be associated with skull developmental stability, and
      genes originally described as buffering genes (e.g., Hspa2) might occupy central
      positions within these networks, where regulatory elements may also play an
      important role. Our results constitute an important step in the exploration of
      the molecular roots of developmental stability and the first empirical evidence
      about its genetic architecture.

PMID- 30209293
TI  - Critical roles of serotonin-oxytocin interaction during the neonatal period in
      social behavior in 15q dup mice with autistic traits.
AB  - Disturbance of neurotransmitters and neuromodulators is thought to underlie the
      pathophysiology of autism spectrum disorder (ASD). Studies of 15q dup mouse
      models of ASD with human 15q11-13 duplication have revealed that restoring
      serotonin (5-HT) levels can partially reverse ASD-related symptoms in adults.
      However, it remains unclear how serotonin contributes to the behavioral symptoms
      of ASD. In contrast, oxytocin (OXT) has been found to involve social and
      affiliative behaviors. In this study, we examined whether serotonin-OXT
      interaction during the early postnatal period plays a critical role in the
      restoration of social abnormality in 15q dup mice. OXT or the 5-HT1A receptor
      agonist 8OH-DPAT treatment from postnatal day 7 (PD7) to PD21 ameliorated social
      abnormality in the three-chamber social interaction test in adult 15q dup mice.
      The effect of 8OH-DPAT was inhibited by blockade of OXT receptors in 15q dup
      mice. Thus, serotonin-OXT interaction via 5-HT1A receptors plays a critical role
      in the normal development of social behavior in 15q dup mice. Therefore,
      targeting serotonin-OXT interaction may provide a novel therapeutic strategy for
      treatment of ASD.

PMID- 30209294
TI  - IL-27 amplifies cytokine responses to Gram-negative bacterial products and
      Salmonella typhimurium infection.
AB  - Cytokine responses from monocytes and macrophages exposed to bacteria are of
      particular importance in innate immunity. Focusing on the impact of the
      immunoregulatory cytokine interleukin (IL)-27 on control of innate immune system
      responses, we examined human immune responses to bacterial products and bacterial
      infection by E. coli and S. typhimurium. Since the effect of IL-27 treatment in
      human myeloid cells infected with bacteria is understudied, we treated human
      monocytes and macrophages with IL-27 and either LPS, flagellin, or bacteria, to
      investigate the effect on inflammatory signaling and cytokine responses. We
      determined that simultaneous stimulation with IL-27 and LPS derived from E. coli
      or S. typhimurium resulted in enhanced IL-12p40, TNF-alpha, and IL-6 expression
      compared to that by LPS alone. To elucidate if IL-27 manipulated the cellular
      response to infection with bacteria, we infected IL-27 treated human macrophages
      with S. typhimurium. While IL-27 did not affect susceptibility to S. typhimurium
      infection or S. typhimurium-induced cell death, IL-27 significantly enhanced
      proinflammatory cytokine production in infected cells. Taken together, we
      highlight a role for IL-27 in modulating innate immune responses to bacterial
      infection.

PMID- 30209295
TI  - Atomistic Peptide Folding Simulations Reveal Interplay of Entropy and Long-Range
      Interactions in Folding Cooperativity.
AB  - Understanding how proteins fold has remained a problem of great interest in
      biophysical research. Atomistic computer simulations using physics-based force
      fields can provide important insights on the interplay of different interactions
      and energetics and their roles in governing the folding thermodynamics and
      mechanism. In particular, generalized Born (GB)-based implicit solvent force
      fields can be optimized to provide an appropriate balance between solvation and
      intramolecular interactions and successfully recapitulate experimental
      conformational equilibria for a set of helical and beta-hairpin peptides. Here,
      we further demonstrate that key thermodynamic properties and their temperature
      dependence obtained from replica exchange molecular dynamics simulations of these
      peptides are in quantitative agreement with experimental results. Useful lessons
      can be learned on how the interplay of entropy and sequentially long-range
      interactions governs the mechanism and cooperativity of folding. These results
      highlight the great potential of high-quality implicit solvent force fields for
      studying protein folding and large-scale conformational transitions.

PMID- 30209298
TI  - Author Correction: TRPS1 shapes YAP/TEAD-dependent transcription in breast cancer
      cells.
AB  - In the original version of this Article, financial support was not fully
      acknowledged. The PDF and HTML versions of the Article have now been corrected to
      include the following: "This work was supported by the Francis Crick Institute,
      which receives its core funding from Cancer Research UK (FC001144), the UK
      Medical Research Council (FC001144), and the Wellcome Trust (FC001144)."
      https://doi.org/10.1038/s41467-018-05370-7 .

PMID- 30209296
TI  - Inactivation of Stat3 and crosstalk of miRNA155-5p and FOXO3a contribute to the
      induction of IGFBP1 expression by beta-elemene in human lung cancer.
AB  - beta-Elemene, an active component of natural plants, has been shown to exhibit
      anticancer properties. However, the detailed mechanism underlying these effects
      has yet to be determined. In this study, we show that beta-elemene inhibits the
      growth of lung cancer cells. Mechanistically, we found that beta-elemene
      decreased the phosphorylation of signal transducer and activator of transcription
      3 (Stat3) and miRNA155-5p mRNA but induced the protein expression of human
      forkhead box class O (FOXO)3a; the latter two were abrogated in cells with
      overexpressed Stat3. Notably, miRNA155-5p mimics reduced FOXO3a luciferase
      reporter activity in the 3-UTR region and protein expression, whereas
      overexpressed FOXO3a countered the reduction of the miRNA155-5p levels by beta
      elemene. Moreover, beta-elemene increased the mRNA and protein expression levels
      as well as promoter activity of insulin-like growth factor-binding protein 1
      (IGFBP1); this finding was not observed in cells with a silenced FOXO3a gene and
      miRNA155-5p mimics. Finally, silencing of IGFBP1 blocked beta-elemene-inhibited
      cell growth. Similar findings were observed in vivo. In summary, our results
      indicate that beta-elemene increases IGFBP1 gene expression via inactivation of
      Stat3 followed by a reciprocal interaction between miRNA155-5p and FOXO3a. This
      effect leads to inhibition of human lung cancer cell growth. These findings
      reveal a novel molecular mechanism underlying the inhibitory effects of beta
      elemene on lung cancer cells.

PMID- 30209297
TI  - PARP-1-dependent RND1 transcription induced by topoisomerase I cleavage complexes
      confers cellular resistance to camptothecin.
AB  - RHO GTPases regulate essential functions such as the organization of the actin
      cytoskeleton. The classic members cycle between an active GTP-bound and an
      inactive GDP-bound conformation whereas atypical members are predominantly GTP
      bound. Besides their well-established role, the classic RHO GTPases RHOB and
      RAC1, are rapidly induced and/or activated by genotoxic stress and contribute to
      the DNA damage response. Here we used camptothecin, a selective topoisomerase I
      (TOP1) inhibitor that stabilizes TOP1 cleavage complexes (TOP1cc), to search for
      other potential early DNA damage-inducible RHO GTPase genes. We identified that
      an atypical RHO GTPase, RND1, is rapidly induced by camptothecin. RND1 induction
      is closely associated with the presence of TOP1cc induced by camptothecin or by
      DNA lesions that elevate TOP1cc levels such as UV and hydrogen peroxide. We
      further demonstrated that camptothecin increases RND1 gene transcription and mRNA
      stability. Camptothecin also increases poly(ADP-ribose) polymerase 1 (PARP-1)
      activity, whose inhibition reduces RND1 transcription. In addition,
      overexpression of RND1 increases PARP-1, suggesting a cross-talk between PARP-1
      and RND1. Finally, RND1 protects cells against camptothecin-induced apoptosis,
      and hence favors cellular resistance to camptothecin. Together, these findings
      highlight RND1 as an atypical RHO GTPase early induced by TOP1cc, and show that
      the TOP1cc-PARP-1-RND1 pathway protects cells against apoptosis induced by
      camptothecin.

PMID- 30209299
TI  - Publisher Correction: Quantum coherence of multiple excitons governs absorption
      cross-sections of PbS/CdS core/shell nanocrystals.
AB  - The original version of this Article contained an error in the seventh sentence
      of the second paragraph of the 'TA amplitudes for double pump-pulse excitation"
      section of the Results, which incorrectly read 'The absorption cross-sections of
      the transitions from the single exciton state to the biexciton and triexciton
      states are denoted by sigma' and sigma'', respectively.' The correct version
      states 'sigma''' in place of 'sigma'''.The ninth and tenth sentences of the same
      paragraph originally incorrectly read 'The most important issue of this work is
      to clarify whether the multiple exciton absorption cross-sections sigma' and
      sigma'' are equal to sigma or not. The black dotted curves in Fig. 3b, c show the
      predicted results of the TA amplitudes by assuming identical cross-sections,
      i.e., sigma = sigma ' = sigma'' = .' The correct version states 'sigma' and
      sigma'' are equal" instead of 'sigma' and sigma'' are equal' and 'sigma = sigma'
      = sigma''' in place of 'sigma = sigma ' = sigma'' = '.This has been corrected in
      both the PDF and HTML versions of the Article.

PMID- 30209301
TI  - Reproducibility: let's get it right from the start.

PMID- 30209300
TI  - Histone acetylation as a new mechanism for bilirubin-induced encephalopathy in
      the Gunn rat.
AB  - Bilirubin neurotoxicity has been studied for decades and has been shown to affect
      various mechanisms via significant modulation of gene expression. This suggests
      that vital regulatory mechanisms of gene expression, such as epigenetic
      mechanisms, could play a role in bilirubin neurotoxicity. Histone acetylation has
      recently received attention in the CNS due to its role in gene modulation for
      numerous biological processes, such as synaptic plasticity, learning, memory,
      development and differentiation. Aberrant epigenetic regulation of gene
      expression in psychiatric and neurodegenerative disorders has also been
      described. In this work, we followed the levels of histone 3 lysine 14
      acetylation (H3K14Ac) in the cerebellum (Cll) of the developing (2, 9, 17 days
      after the birth) and adult Gunn rat, the natural model for neonatal
      hyperbilirubinemia and kernicterus. We observed an age-specific alteration of the
      H3K14Ac in the hyperbilirubinemic animals. The GeneOntology analysis of the
      H3K14Ac linked chromatin revealed that almost 45% of H3K14Ac ChiP-Seq TSS
      promoter genes were involved in CNS development including maturation and
      differentiation, morphogenesis, dendritogenesis, and migration. These data
      suggest that the hallmark Cll hypoplasia in the Gunn rat occurs also via
      epigenetically controlled mechanisms during the maturation of this brain
      structure, unraveling a novel aspect of the bilirubin-induced neurotoxicity.

PMID- 30209302
TI  - Caveolin-1 impairs PKA-DRP1-mediated remodelling of ER-mitochondria communication
      during the early phase of ER stress.
AB  - Close contacts between endoplasmic reticulum and mitochondria enable reciprocal
      Ca2+ exchange, a key mechanism in the regulation of mitochondrial bioenergetics.
      During the early phase of endoplasmic reticulum stress, this inter-organellar
      communication increases as an adaptive mechanism to ensure cell survival. The
      signalling pathways governing this response, however, have not been
      characterized. Here we show that caveolin-1 localizes to the endoplasmic
      reticulum-mitochondria interface, where it impairs the remodelling of endoplasmic
      reticulum-mitochondria contacts, quenching Ca2+ transfer and rendering
      mitochondrial bioenergetics unresponsive to endoplasmic reticulum stress. Protein
      kinase A, in contrast, promotes endoplasmic reticulum and mitochondria
      remodelling and communication during endoplasmic reticulum stress to promote
      organelle dynamics and Ca2+ transfer as well as enhance mitochondrial
      bioenergetics during the adaptive response. Importantly, caveolin-1 expression
      reduces protein kinase A signalling, as evidenced by impaired phosphorylation and
      alterations in organelle distribution of the GTPase dynamin-related protein 1,
      thereby enhancing cell death in response to endoplasmic reticulum stress. In
      conclusion, caveolin-1 precludes stress-induced protein kinase A-dependent
      remodelling of endoplasmic reticulum-mitochondria communication.

PMID- 30209304
TI  - Achromatic linear polarization rotators by tandem twisted nematic liquid crystal
      cells.
AB  - An achromatic linear polarization rotator based on a tandem-2phi-twisted nematic
      liquid crystal cell (tandem-2phi-TNLC cell, where 2phi represents the total
      twisted angle) is theoretically analyzed and experimentally demonstrated. The
      tandem-2phi-TNLC cell comprises two conventional phi-TNLC cells with the required
      arrangement that the LC director close to the last layer of the first phi-TNLC
      cell should be perpendicular to that close to the first layer of the second phi
      TNLC cell. With such a simple combination, the TNLC performances are considerably
      improved. According to the experimental results and theoretical analyses by Jones
      Calculus, the tandem-2phi-TNLC polarization rotator with suitable parameters is
      achromatic and insensitive to the polarization plane of incident light. Such
      properties provide these polarization rotators with potential for practical
      applications.

PMID- 30209303
TI  - Augmentation of vaccine-induced humoral and cellular immunity by a physical
      radiofrequency adjuvant.
AB  - Protein/subunit vaccines often require external adjuvants to induce protective
      immunity. Due to the safety concern of chemical adjuvants, physical adjuvants
      were recently explored to boost vaccination. Physical adjuvants use physical
      energies rather than chemicals to stimulate tissue stress and endogenous danger
      signal release to boost vaccination. Here we present the safety and potency of
      non-invasive radiofrequency treatment to boost intradermal vaccination in murine
      models. We show non-invasive radiofrequency can increase protein antigen-induced
      humoral and cellular immune responses with adjuvant effects comparable to widely
      used chemical adjuvants. Radiofrequency adjuvant can also safely boost pandemic
      2009 H1N1 influenza vaccination with adjuvant effects comparable to MF59-like
      AddaVax adjuvant. We find radiofrequency adjuvant induces heat shock protein 70
      (HSP70) release and activates MyD88 to mediate the adjuvant effects. Physical
      radiofrequency can potentially be a safe and potent adjuvant to augment
      protein/subunit vaccine-induced humoral and cellular immune responses.

PMID- 30209305
TI  - Association of body mass index and uncontrolled blood pressure with
      cardiovascular mortality in peritoneal dialysis patients.
AB  - The association of body mass index (BMI) and blood pressure (BP) control and
      their interaction with cardiovascular (CV) mortality in continuous ambulatory
      peritoneal dialysis (CAPD) patients is unclear. We retrospectively analyzed a
      consecutive series of 1595 incident CAPD patients with hypertension from 2006 to
      2013, and followed up through December 2015. The BMI was categorized according to
      the World Health Organization classification for Asian population. Binary
      logistic regression was used to assess the relationship between BMI and BP
      control. Cox's proportional hazards models and competing risk analyses were
      performed to examine the nassociation of BMI and BP control with CV mortality. In
      the entire cohort, obesity was unlikely related to increased risk of uncontrolled
      BP. However, the adjusted hazard ratio (AHR) of CV mortality was increased in
      individuals with obesity when compared to those with normal weight (AHR 1.56; 95%
      confidence interval (CI) 1.04-2.34) and in individuals with uncontrolled BP when
      compared to those with controlled BP (AHR 1.39; (1.02-1.89)). Subgroup analyses
      showed that the combination of obesity and uncontrolled BP was associated with an
      increased risk for CV death, when compared to normal weight subjects with
      uncontrolled BP (AHR 2.35; (1.43-3.86)). Further, subjects with obesity and
      uncontrolled BP had a nearly threefold increase in risk (AHR 2.57; (1.57-4.20))
      for CV death compared to subjects with neither risk factor. These associations
      persisted in competing risk analyses. In conclusion, the association of obesity
      with CV mortality was likely to vary with hypertension status among CAPD
      patients.

PMID- 30209306
TI  - Peridialysis BP levels and risk of all-cause mortality: a dose-response meta
      analysis.
AB  - Blood pressure (BP) management posed great challenge in hemodialysis (HD)
      population. We conducted a dose-response meta-analysis to investigate the
      quantitative features and the potential threshold effect of the associations
      between peridialysis BP levels and all-cause mortality risk in HD population. We
      searched all of the prospective cohort studies (published before 18 March 2017)
      on the associations between peridialysis BP levels and all-cause mortality risk.
      A total of 229,688 prevalent HD patients from 8 studies were included.
      Significant non-linear associations were noted between peridialytic BP levels and
      all-cause mortality risk. Significant increased risk of death was found in four
      peridialysis BP ranges, that is, low levels of predialysis SBP (<135 mmHg, 140
      mmHg as the reference), two extremes of predialysis DBP (<55 and >95 mmHg, 90
      mmHg as the reference), high levels of postdialysis SBP (>180 mmHg, 130 mmHg as
      the reference), and low levels of postdialysis DBP (<75 mmHg, 80 mmHg as the
      reference). Threshold effect was determined in the associations between
      peridialysis BP and all-cause mortality risk, and potential BP thresholds were
      identified (149 mmHg for predialysis SBP, 79 mmHg for predialysis DBP, 147 mmHg
      for postdialysis SBP and 76 mmHg for postdialysis DBP). In conclusion, the
      proposed peridialysis BP ranges and the threshold values could help clinicians
      identify high risk HD patients. The interpretation of the peridialysis BP
      mortality associations should be based on the features of HD population
      (especially the cardiovascular conditions, volume status and the dialysis
      vintage).

PMID- 30209308
TI  - Changing mutational patterns.

PMID- 30209307
TI  - Publisher Correction: The molecular landscape of head and neck cancer.
AB  - The article as originally published contained errors in Figure 3. The direction
      of the arrows associated with the labels for p53 and RB were incorrect. This has
      now been corrected in all versions of the article.

PMID- 30209310
TI  - Disordered interactions.

PMID- 30209311
TI  - Comparison of frequency and strain-rate domain mechanical characterization.
AB  - Indentation is becoming increasingly popular to test soft tissues and
      (bio)materials. Each material exhibits an unknown intrinsic "mechanical
      behaviour". However, limited consensus on its "mechanical properties" (i.e.
      quantitative descriptors of mechanical behaviour) is generally present in the
      literature due to a number of factors, which include sample preparation, testing
      method and analysis model chosen. Viscoelastic characterisation - critical in
      applications subjected to dynamic loading conditions - can be performed in either
      the time- or frequency-domain. It is thus important to selectively investigate
      whether the testing domain affects the mechanical results or not. We recently
      presented an optomechanical indentation tool which enables both strain-rate (nano
      [Formula: see text]) and frequency domain (DMA) measurements while keeping the
      sample under the same physical conditions and eliminating any other variability
      factor. In this study, a poly(dimethylsiloxane) sample was characterised with our
      system. The DMA data were inverted to the time-domain through integral
      transformations and then directly related to nano-[Formula: see text] strain-rate
      dependent results, showing that, even though the data do not perfectly overlap,
      there is an excellent correlation between them. This approach indicates that one
      can convert an oscillatory measurement into a strain-rate one and still capture
      the trend of the "mechanical behaviour" of the sample investigated.

PMID- 30209309
TI  - Structural basis for importin alpha 3 specificity of W proteins in Hendra and
      Nipah viruses.
AB  - Seven human isoforms of importin alpha mediate nuclear import of cargo in a
      tissue- and isoform-specific manner. How nuclear import adaptors differentially
      interact with cargo harbouring the same nuclear localisation signal (NLS) remains
      poorly understood, as the NLS recognition region is highly conserved. Here, we
      provide a structural basis for the nuclear import specificity of W proteins in
      Hendra and Nipah viruses. We determine the structural interfaces of these cargo
      bound to importin alpha1 and alpha3, identifying a 2.4-fold more extensive
      interface and > 50-fold higher binding affinity for importin alpha3. Through the
      design of importin alpha1 and alpha3 chimeric and mutant proteins, together with
      structures of cargo-free importin alpha1 and alpha3 isoforms, we establish that
      the molecular basis of specificity resides in the differential positioning of the
      armadillo repeats 7 and 8. Overall, our study provides mechanistic insights into
      a range of important nucleocytoplasmic transport processes reliant on isoform
      adaptor specificity.

PMID- 30209312
TI  - Bioinspired 3D structures with programmable morphologies and motions.
AB  - Living organisms use spatially controlled expansion and contraction of soft
      tissues to achieve complex three-dimensional (3D) morphologies and movements and
      thereby functions. However, replicating such features in man-made materials
      remains a challenge. Here we report an approach that encodes 2D hydrogels with
      spatially and temporally controlled growth (expansion and contraction) to create
      3D structures with programmed morphologies and motions. This approach uses
      temperature-responsive hydrogels with locally programmable degrees and rates of
      swelling and shrinking. This method simultaneously prints multiple 3D structures
      with custom design from a single precursor in a one-step process within 60 s. We
      suggest simple yet versatile design rules for creating complex 3D structures and
      a theoretical model for predicting their motions. We reveal that the spatially
      nonuniform rates of swelling and shrinking of growth-induced 3D structures
      determine their dynamic shape changes. We demonstrate shape-morphing 3D
      structures with diverse morphologies, including bioinspired structures with
      programmed sequential motions.

PMID- 30209314
TI  - Patterns of posterior ocular complications in myopic eyes of Indian population.
AB  - This is a retrospective study aimed to investigate the patterns of myopic fundus
      complications in Indian children and young adults. Electronic medical records of
      29,592 patients, aged 10-40 years, who visited L V Prasad Eye Institute between
      1st January to 31st December 2016 were analysed in the study. Data such as age,
      gender, refractive error and various pathologic lesions of posterior globe were
      considered for analysis. Among all the patients with different types of
      refractive errors, myopia was found in 47.4%, high myopia in 6.8% and pathologic
      myopia in 2.2%. There was no trend of the increased prevalence of pathologic
      myopia with increasing age, except for a significant difference between the
      children aged 10-15 years (2.7%) and those aged more than 15 years (>4%). .
      Although, the overall pattern of pathologic lesions was similar across different
      grades of myopia (2.5% in low myopes vs. 2.2% in severe myopes), lesions like
      staphyloma and retinal detachment increased with increasing degree of myopia. The
      proportion of pathologic lesions across different grades of myopia suggests the
      necessity for careful peripheral fundus examinations irrespective of the degree
      of myopia for better management and prognostic purposes.

PMID- 30209313
TI  - Differential processing of HIV envelope glycans on the virus and soluble
      recombinant trimer.
AB  - As the sole target of broadly neutralizing antibodies (bnAbs) to HIV, the
      envelope glycoprotein (Env) trimer is the focus of vaccination strategies
      designed to elicit protective bnAbs in humans. Because HIV Env is densely
      glycosylated with 75-90 N-glycans per trimer, most bnAbs use or accommodate them
      in their binding epitope, making the glycosylation of recombinant Env a key
      aspect of HIV vaccine design. Upon analysis of three HIV strains, we here find
      that site-specific glycosylation of Env from infectious virus closely matches
      Envs from corresponding recombinant membrane-bound trimers. However, viral Envs
      differ significantly from recombinant soluble, cleaved (SOSIP) Env trimers,
      strongly impacting antigenicity. These results provide a benchmark for virus Env
      glycosylation needed for the design of soluble Env trimers as part of an overall
      HIV vaccine strategy.

PMID- 30209316
TI  - Nitrogen and phosphorus stoichiometry of Schima superba under nitrogen
      deposition.
AB  - In this study, leaf nitrogen (N) and phosphorus (P) stoichiometry were used as
      indicators of nitrogen saturation and to assess ecosystem nutrient limitations.
      Schima superba, a representative and widely distributed dominant evergreen
      broadleaf tree species of the subtropical forests in southern China, was used for
      this purpose. A nutrient-addition experiment and a field survey were conducted to
      test the responses of trees from different provenances to N deposition. The
      relationships between leaf N and P stoichiometry and biomass, nutrient
      limitation, and soil N:P were analyzed. There was a relationship between leaf N,
      P, N:P, soil N:P and plant dry biomass. A threshold leaf N:P ratio (16.3) divided
      the five provenances into different nutrient-limitation classes that were related
      to the soil N:P ratio or N deposition. The leaf N:P ratio provided an indication
      of P limitation. A higher soil P level reduced the N deposition effect on plant
      growth. The leaf N:P ratio of individuals from different provenances can be used
      as a predictor of nutrient limitation, and this was related to the soil N:P
      ratio.

PMID- 30209315
TI  - Novel digital signatures of tissue phenotypes for predicting distant metastasis
      in colorectal cancer.
AB  - Distant metastasis is the major cause of death in colorectal cancer (CRC).
      Patients at high risk of developing distant metastasis could benefit from
      appropriate adjuvant and follow-up treatments if stratified accurately at an
      early stage of the disease. Studies have increasingly recognized the role of
      diverse cellular components within the tumor microenvironment in the development
      and progression of CRC tumors. In this paper, we show that automated analysis of
      digitized images from locally advanced colorectal cancer tissue slides can
      provide estimate of risk of distant metastasis on the basis of novel tissue
      phenotypic signatures of the tumor microenvironment. Specifically, we determine
      what cell types are found in the vicinity of other cell types, and in what
      numbers, rather than concentrating exclusively on the cancerous cells. We then
      extract novel tissue phenotypic signatures using statistical measurements about
      tissue composition. Such signatures can underpin clinical decisions about the
      advisability of various types of adjuvant therapy.

PMID- 30209317
TI  - Author Correction: Post-treatment with PT302, a long-acting Exendin-4 sustained
      release formulation, reduces dopaminergic neurodegeneration in a 6
      Hydroxydopamine rat model of Parkinson's disease.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 30209318
TI  - Structural insights into antigen recognition of an anti-beta-(1,6)-beta-(1,3)-D
      glucan antibody.
AB  - Schizophyllan (SCH) is a high molecular weight homopolysaccharide composed of a
      beta-(1,3)-D-glucan main chain with branching beta-(1,6)-bound D-glucose
      residues. It forms triple helices that are highly stable towards heat and extreme
      pH, which provides SCH with interesting properties for industrial and medical
      applications. The recombinant anti-SCH antibody JoJ48C11 recognizes SCH and
      related beta-(1,6)-branched beta-(1,3)-D-glucans, but details governing its
      specificity are not known. Here, we fill this gap by determining crystal
      structures of the antigen binding fragment (Fab) of JoJ48C11 in the apo form and
      in complex with the unbranched beta-(1,3)-D-glucose hexamer laminarihexaose 3.0
      and 2.4 A resolution, respectively. Together with docking studies, this allowed
      construction of a JoJ48C11/triple-helical SCH complex, leading to the
      identification of eight amino acid residues of JoJ48C11 (Tyr27H, His35H, Trp47H,
      Trp100H, Asp105H; Asp49L, Lys52L, Trp90L) that contribute to the recognition of
      glucose units from all three chains of the SCH triple helix. The importance of
      these amino acids was confirmed by mutagenesis and ELISA-based analysis. Our work
      provides an explanation for the specific recognition of triple-helical beta-(1,6)
      branched beta-(1,3)-D-glucans by JoJ48C11 and provides another structure example
      for anti-carbohydrate antibodies.

PMID- 30209319
TI  - Mercury and arsenic attenuate canonical and non-canonical NLRP3 inflammasome
      activation.
AB  - Exposure to heavy metals can cause several diseases associated with the immune
      system. Although the effects of heavy metals on production of inflammatory
      cytokines have been previously studied, the role of heavy metals in inflammasome
      activation remains poorly studied. The inflammasome is an intracellular multi
      protein complex that detects intracellular danger signals, resulting in
      inflammatory responses such as cytokine maturation and pyroptosis. In this study,
      we elucidated the effects of four heavy metals, including cadmium (Cd), mercury
      (Hg), arsenic (As), and lead (Pb), on the activation of NLRP3, NLRC4, and AIM2
      inflammasomes. In our results, mercury and arsenic inhibited interleukin (IL)
      1beta and IL-18 secretion resulting from canonical and non-canonical NLRP3
      inflammasome activation in macrophages and attenuated elevation of serum IL-1beta
      in response to LPS treatment in mice. In the mechanical studies, mercury
      interrupted production of mitochondrial reactive oxygen species, release of
      mitochondrial DNA, and activity of recombinant caspase-1, whereas arsenic down
      regulated expression of promyelocytic leukemia protein. Both mercury and arsenic
      inhibited Asc pyroptosome formation and gasdermin D cleavage. Thus, we suggest
      that exposure to mercury and/or arsenic could disrupt inflammasome-mediated
      inflammatory responses, which might cause unexpected side effects.

PMID- 30209321
TI  - A photonic frequency discriminator based on a two wavelength delayed self
      heterodyne interferometer for low phase noise tunable micro/mm wave synthesis.
AB  - Low phase noise frequency synthesizers are of paramount interest in many areas of
      micro-mm wave technology, encompassing for example advanced wireless
      communication, radar, radio-astronomy, and precision instrumentation. Although
      this broad research field is not bereft of methods for the generation of either
      low phase noise micro- or mm waves, no universal system applicable to low phase
      noise generation for micro and mm waves has yet been demonstrated. Here we
      propose a new photonic frequency discriminator based on a two wavelength delayed
      self-heterodyne interferometer which is compatible with such an objective. The
      photonic frequency discriminator can be a reference both for micro and mm waves
      to lower their phase noise. As a proof-of-concept, we demonstrate a low phase
      noise tunable OEO (6-18 GHz) and locking of a heterodyne beat between two cw
      lasers (10-400 GHz) with low relative phase noise. The required components for
      the photonic frequency discriminator are off-the-shelf and can be readily
      assembled. We believe this new type of photonic frequency discriminator will
      enable a new generation of universal precision tunable sources for the X, K, V, W
      and mm-bands and beyond.

PMID- 30209322
TI  - Complexity, rate, and scale in sliding friction dynamics between a finger and
      textured surface.
AB  - Sliding friction between the skin and a touched surface is highly complex, but
      lies at the heart of our ability to discriminate surface texture through touch.
      Prior research has elucidated neural mechanisms of tactile texture perception,
      but our understanding of the nonlinear dynamics of frictional sliding between the
      finger and textured surfaces, with which the neural signals that encode texture
      originate, is incomplete. To address this, we compared measurements from human
      fingertips sliding against textured counter surfaces with predictions of
      numerical simulations of a model finger that resembled a real finger, with
      similar geometry, tissue heterogeneity, hyperelasticity, and interfacial
      adhesion. Modeled and measured forces exhibited similar complex, nonlinear
      sliding friction dynamics, force fluctuations, and prominent regularities related
      to the surface geometry. We comparatively analysed measured and simulated forces
      patterns in matched conditions using linear and nonlinear methods, including
      recurrence analysis. The model had greatest predictive power for faster sliding
      and for surface textures with length scales greater than about one millimeter.
      This could be attributed to the the tendency of sliding at slower speeds, or on
      finer surfaces, to complexly engage fine features of skin or surface, such as
      fingerprints or surface asperities. The results elucidate the dynamical forces
      felt during tactile exploration and highlight the challenges involved in the
      biological perception of surface texture via touch.

PMID- 30209320
TI  - Draft genome sequence of first monocot-halophytic species Oryza coarctata reveals
      stress-specific genes.
AB  - Oryza coarctata (KKLL; 2n = 4x = 48, 665 Mb) also known as Porteresia coarctata
      is an extreme halophyte species of genus Oryza. Using Illumina and Nanopore
      reads, we achieved the assembled genome size of 569.9 Mb, accounting 85.69% of
      the estimated genome size with N50 of 1.85 Mb and 19.89% repetitive region. We
      also found 230,968 simple sequence repeats (SSRs) and 5,512 non-coding RNAs
      (ncRNAs). The functional annotation of predicted 33,627 protein-coding genes and
      4,916 transcription factors revealed that high salinity adaptation of this
      species is due to the exclusive or excessive presence of stress-specific genes as
      compared to rice. We have identified 8 homologs to salt-tolerant SOS1 genes, one
      of the three main components of salt overly sensitive (SOS) signal pathway. On
      the other hand, the phylogenetic analysis of the assembled chloroplast (134.75
      kb) and mitochondrial genome (491.06 kb) favours the conservative nature of these
      organelle genomes within Oryza taxon.

PMID- 30209323
TI  - Polymer-Silica Hybrid On-Chip Amplifier with Vertical Pumping Method.
AB  - This article demonstrates a multilayer polymer-silica hybrid on-chip amplifier
      combining mode division multiplexing method. The multilayer amplifier consists of
      a pumping silica waveguide and an amplifying polymer waveguide. The pumping
      waveguide possesses the stability and the high damage threshold. The amplifying
      waveguide takes the advantages of the high compatibility and the high doping
      rate. The vertical pump of mode division multiplexing method can introduce the
      pumping light into the amplifying waveguide at any desired position of the chip.
      By the isolation method between signal and pumping light, the pumping light can
      be coupled into the amplifying waveguide, while the signal light cannot be
      coupled into the pumping waveguide. The parameters of doping rates, waveguide
      lengths, overlap factors, coupling parameters are calculated to optimize the gain
      characteristics of the amplifier. The amplifier with three position-optimized
      pumping light was designed achieving a maximum gain of 33.89 dB/cm with a
      waveguide length of 6 cm, a signal power of 0.1 mW and a pumping power of 300 mW.
      This polymer-silica hybrid amplifier is promising for the on-chip loss
      compensation of the 3D photonic integrated circuits and all optical transistors.

PMID- 30209325
TI  - Receptor replacement.

PMID- 30209324
TI  - Systems pharmacology-based exploration reveals mechanisms of anti-steatotic
      effects of Jiang Zhi Granule on non-alcoholic fatty liver disease.
AB  - Non-alcoholic fatty liver disease (NAFLD), which is in parallel with the obesity
      epidemic, accounts for a large amount of all chronic liver disease. Jiang Zhi
      Granule (JZG), a clinically used herbal formula, is developed in accordance with
      traditional Chinese medicine (TCM) pathogenesis for treating patients with NAFLD.
      In previous studies, the anti-steatotic effects of JZG against NAFLD have been
      demonstrated, and in this study, a systems pharmacology approach was used to
      explore the pharmacological mechanisms of JZG by predicting the active compounds
      within the herbal formula and their corresponding therapeutic targets. Its
      therapeutic efficacy was confirmed in the beginning of this study, and JZG was
      shown to significantly improve hepatic dysfunction and lipid droplet accumulation
      in PA-treated hepatocytes. Systems pharmacology was then performed to identify
      the active compounds in as well as to predict the therapeutic targets of this
      Chinese herbal prescription. Enrichment analyses indicated that the mechanisms of
      the anti-steatotic effects of JZG against NAFLD might be associated with lipid
      droplet degradation via autophagy, and a series of in vitro and in vivo
      validation experiments was subsequently performed to confirm that JZG could
      activate autophagy though the mTOR signalling to improve NAFLD.

PMID- 30209327
TI  - Mindful breath awareness meditation facilitates efficiency gains in brain
      networks: A steady-state visually evoked potentials study.
AB  - The beneficial effects of mindfulness-based therapeutic interventions have
      stimulated a rapidly growing body of scientific research into underlying
      psychological processes. Resulting evidence indicates that engaging with
      mindfulness meditation is associated with increased performance on a range of
      cognitive tasks. However, the mechanisms promoting these improvements require
      further investigation. We studied changes in behavioural performance of 34
      participants during a multiple object tracking (MOT) task that taps core
      cognitive processes, namely sustained selective visual attention and spatial
      working memory. Concurrently, we recorded the steady-state visually evoked
      potential (SSVEP), an EEG signal elicited by the continuously flickering moving
      objects, and indicator of attentional engagement. Participants were tested before
      and after practicing eight weeks of mindful breath awareness meditation or
      progressive muscle relaxation as active control condition. The meditation group
      improved their MOT-performance and exhibited a reduction of SSVEP amplitudes,
      whereas no such changes were observed in the relaxation group. Neither group
      changed in self-reported positive affect and mindfulness, while a marginal
      increase in negative affect was observed in the mindfulness group. This novel way
      of combining MOT and SSVEP provides the important insight that mindful breath
      awareness meditation may lead to refinements of attention networks, enabling more
      efficient use of attentional resources.

PMID- 30209326
TI  - Gene expression analysis of Atlantic salmon gills reveals mucin 5 and interleukin
      4/13 as key molecules during amoebic gill disease.
AB  - Amoebic gill disease (AGD) is one of the main diseases affecting Atlantic salmon
      (Salmo salar L.) mariculture. Hallmarks of AGD are hyperplasia of the lamellar
      epithelium and increased production of gill mucus. This study investigated the
      expression of genes involved in mucus secretion, cell cycle regulation, immunity
      and oxidative stress in gills using a targeted 21-gene PCR array. Gill samples
      were obtained from experimental and natural Neoparamoeba perurans infections, and
      sampling points included progressive infection stages and post-freshwater
      treatment. Up-regulation of genes related to mucin secretion and cell
      proliferation, and down-regulation of pro-inflammatory and pro-apoptotic genes
      were associated with AGD severity, while partial restoration of the gill
      homeostasis was detected post-treatment. Mucins and Th2 cytokines accoun ted for
      most of the variability observed between groups highlighting their key role in
      AGD. Two mucins (muc5, muc18) showed differential regulation upon disease.
      Substantial up-regulation of the secreted muc5 was detected in clinical AGD, and
      the membrane bound muc18 showed an opposite pattern. Th2 cytokines, il4/13a and
      il4/13b2, were significantly up-regulated from 2 days post-infection onwards, and
      changes were lesion-specific. Despite the differences between experimental and
      natural infections, both yielded comparable results that underline the importance
      of the studied genes in the respiratory organs of fish, and during AGD
      progression.

PMID- 30209328
TI  - A power-free, parallel loading microfluidic reactor array for biochemical
      screening.
AB  - This paper presents a power-free, self-contained microfluidic device in which a
      number of nanoliter-sized droplets can be parallelly and accurately metered and
      mixed for high-throughput analysis and/or portable systems. In this system, the
      absorption of air by pre-degassed PDMS and the change of capillary force due to
      sudden narrowing of the channel cross-section provide the mechanism for
      actuating, metering and mixing the flow of fluid in the microfluidic channels and
      chambers. With an array of channels and capillary valves combined with an array
      of pre-degassed PDMS pump chambers, the device can perform multiple liquid
      dispensing and mixing in parallel, and its performance and reproducibility are
      also evaluated. As a practical application, the proposed device is used to screen
      crystallization conditions of lysozyme. This device needs neither external power
      nor complex instruments for fluid handling. Thus, it offers an easy-to-use,
      inexpensive and power-free way to perform multiple nanoliter-volume distinct
      reactions in parallel format and should be ideally suitable for individual
      laboratories for various applications such as enzyme assay, protein
      crystallization, drug discovery, and combinatorial chemistry.

PMID- 30209329
TI  - Surface Proximity Effect, Imprint Memory of Ferroelectric Twins, and Tweed in the
      Paraelectric Phase of BaTiO3.
AB  - We have used energy-filtered photoemission electron microscopy (PEEM) at the
      photoemission threshold to carry out a microscopic scale characterization of the
      surface charge and domain structure of the (001) surface in BaTiO3. Signatures of
      ferroelectric and ferroelastic domains, and tweed, dominate the surface structure
      of BaTiO3 at room temperature. The surface ferroic signatures are maintained on
      heating to temperature (~550 K), well above the transition temperature (393 K).
      This surface proximity effect provides the mechanism for memory of the bulk
      ferroelectric domain arrangement up to 150 K above TC and thus can be considered
      as a robust fingerprint of the ferroelectric state near the surface. Self
      reversal of polarization is observed for the tweed below TC and for the surface
      domains above TC. Annealing at higher temperature triggers the dynamic tweed
      which in turn allows a full reorganization of the ferroic domain configuration.

PMID- 30209330
TI  - Origin of relationship between ferromagnetic response and damage in stretched
      systems.
AB  - This article presents a study whose purpose is to elucidate the damage effects in
      thin films on their magnetic response. Co40Fe40B20 and Ni80Fe20 films of
      different nanometric thicknesses were stretched by more than 10% and in situ
      probed by atomic force microscopy measurements to determine their irreversible
      mechanical behavior (multi-cracking, buckling). Once these phenomena have been
      well identified, magnetic behavior of these stretched systems has been studied by
      ferromagnetic resonance to measure resulting magnetic anisotropy and damping
      evolutions. All of these experimental studies show that the magnetic properties
      are mainly affected by the stresses generated during the damage but not by the
      local discontinuities induced by the numerous cracks and buckles. This is in
      particular confirmed by the almost zero sensitivity to the damage of the magnetic
      properties of Ni80Fe20 alloy which is known for its vanishing magnetostriction.

PMID- 30209332
TI  - The lineage-specific, intrinsically disordered N-terminal extension of monothiol
      glutaredoxin 1 from trypanosomes contains a regulatory region.
AB  - Glutaredoxins (Grx) are small proteins conserved throughout all the kingdoms of
      life that are engaged in a wide variety of biological processes and share a
      common thioredoxin-fold. Among them, class II Grx are redox-inactive proteins
      involved in iron-sulfur (FeS) metabolism. They contain a single thiol group in
      their active site and use low molecular mass thiols such as glutathione as ligand
      for binding FeS-clusters. In this study, we investigated molecular aspects of
      1CGrx1 from the pathogenic parasite Trypanosoma brucei brucei, a mitochondrial
      class II Grx that fulfills an indispensable role in vivo. Mitochondrial 1CGrx1
      from trypanosomes differs from orthologues in several features including the
      presence of a parasite-specific N-terminal extension (NTE) whose role has yet to
      be elucidated. Previously we have solved the structure of a truncated form of
      1CGrx1 containing only the conserved glutaredoxin domain but lacking the NTE. Our
      aim here is to investigate the effect of the NTE on the conformation of the
      protein. We therefore solved the NMR structure of the full-length protein, which
      reveals subtle but significant differences with the structure of the NTE-less
      form. By means of different experimental approaches, the NTE proved to be
      intrinsically disordered and not involved in the non-redox dependent protein
      dimerization, as previously suggested. Interestingly, the portion comprising
      residues 65-76 of the NTE modulates the conformational dynamics of the
      glutathione-binding pocket, which may play a role in iron-sulfur cluster assembly
      and delivery. Furthermore, we disclosed that the class II-strictly conserved loop
      that precedes the active site is critical for stabilizing the protein structure.
      So far, this represents the first communication of a Grx containing an
      intrinsically disordered region that defines a new protein subgroup within class
      II Grx.

PMID- 30209333
TI  - Long-reach 60-GHz MMWoF link with free-running laser diodes beating.
AB  - With the remote beating of two mutually incoherent laser carriers, the local
      oscillator-free long-reach millimeter-wave over fiber (MMWoF) link at 60-GHz band
      is demonstrated. The unique schemes of the proposed MMWoF are the wavelength
      locked colorless laser diode (CLD) modulator, the mutually incoherent optical
      carrier for heterodyne MMW generation, and the square-law power envelope
      detection at receiving end. By directly encoding the single-mode with the CLD
      modulator, the single-carrier modulated QAM-OFDM data is achieved to release the
      RF power fading after fiber transmission. The mutually incoherent laser beating
      enables the optical heterodyne MMW generation with two independent optical
      carriers, which provides the advantages of local-oscillator-free operation and
      rules out the requirement of dual-mode optical carrier delivery from central
      office. At the wireless receiving end, the received QAM-OFDM data is self-down
      converted to the baseband by employing the square-law power envelope detection.
      This eliminates the requirement of local oscillator and rules out the influence
      of the MMW carrier frequency fluctuation between two mutually incoherent lasers
      (used at central office and remote node), which effectively provides the MMW
      carrier immunity against the down-conversion instability caused by clock jitter
      or carrier incoherence. This architecture ensures the transmission of 16.5-Gbit/s
      32-QAM OFDM data over 50 km in SMF and 3 m in free-space with the FEC
      certificated error vector magnitude of 12%, signal-to-noise ratio (SNR) of 18.4
      dB, and bit error rate of 3.8 * 10-3. For multi-channel DWDM-PON applications,
      the proposed local-oscillator-free MMWoF link can successfully perform 11 DWDM
      channels of 32-QAM OFDM data access at 16.5 Gbit/s per channel via the wavelength
      controlling of the CLD modulation stage and the detuning of the beating carrier
      at remote node.

PMID- 30209331
TI  - Genome-wide association meta-analysis of coronary artery disease and
      periodontitis reveals a novel shared risk locus.
AB  - Evidence for a shared genetic basis of association between coronary artery
      disease (CAD) and periodontitis (PD) exists. To explore the joint genetic basis,
      we performed a GWAS meta-analysis. In the discovery stage, we used a German
      aggressive periodontitis sample (AgP-Ger; 680 cases vs 3,973 controls) and the
      CARDIoGRAMplusC4D CAD meta-analysis dataset (60,801 cases vs 123,504 controls).
      Two SNPs at the known CAD risk loci ADAMTS7 (rs11634042) and VAMP8 (rs1561198)
      passed the pre-assigned selection criteria (PAgP-Ger < 0.05; PCAD < 5 * 10-8;
      concordant effect direction) and were replicated in an independent GWAS meta
      analysis dataset of PD (4,415 cases vs 5,935 controls). SNP rs1561198 showed
      significant association (PD[Replication]: P = 0.008 OR = 1.09, 95% CI = [1.02
      1.16]; PD [Discovery + Replication]: P = 0.0002, OR = 1.11, 95% CI = [1.05
      1.17]). For the associated haplotype block, allele specific cis-effects on VAMP8
      expression were reported. Our data adds to the shared genetic basis of CAD and PD
      and indicate that the observed association of the two disease conditions cannot
      be solely explained by shared environmental risk factors. We conclude that the
      molecular pathway shared by CAD and PD involves VAMP8 function, which has a role
      in membrane vesicular trafficking, and is manipulated by pathogens to corrupt
      host immune defense.

PMID- 30209334
TI  - Interleukin-17D and Nrf2 mediate initial innate immune cell recruitment and
      restrict MCMV infection.
AB  - Innate immune cells quickly infiltrate the site of pathogen entry and not only
      stave off infection but also initiate antigen presentation and promote adaptive
      immunity. The recruitment of innate leukocytes has been well studied in the
      context of extracellular bacterial and fungal infection but less during viral
      infections. We have recently shown that the understudied cytokine Interleukin
      (IL)-17D can mediate neutrophil, natural killer (NK) cell and monocyte
      infiltration in sterile inflammation and cancer. Herein, we show that early
      immune cell accumulation at the peritoneal site of infection by mouse
      cytomegalovirus (MCMV) is mediated by IL-17D. Mice deficient in IL-17D or the
      transcription factor Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), an
      inducer of IL-17D, featured an early decreased number of innate immune cells at
      the point of viral entry and were more susceptible to MCMV infection.
      Interestingly, we were able to artificially induce innate leukocyte infiltration
      by applying the Nrf2 activator tert-butylhydroquinone (tBHQ), which rendered mice
      less susceptible to MCMV infection. Our results implicate the Nrf2/IL-17D axis as
      a sensor of viral infection and suggest therapeutic benefit in boosting this
      pathway to promote innate antiviral responses.

PMID- 30209336
TI  - Differential Effect of HCV Eradication and Fibrosis Grade on Hepatocellular
      Carcinoma and All-cause Mortality.
AB  - Whether a sustained virological response (SVR) improves long-term outcomes in
      chronic hepatitis C patients with earlier-stage fibrosis has not been
      established. We investigated the differential effect of SVR on the risk of
      outcomes according to hepatic fibrosis grade. Fibrosis grade was categorised
      using FIB-4: <1.45, low-probability of significant fibrosis; 1.45-3.25,
      intermediate-probability; and >=3.25, high-probability. Primary and secondary
      endpoints were hepatocellular carcinoma (HCC) occurrence and death, respectively.
      Among 1,373 included chronic hepatitis C patients, 744 patients were treated with
      interferon-based or -free regimens and 622 (83.6%) achieved SVR. SVR was
      independently associated with lower risk of HCC (vs. untreated: adjusted hazard
      ratio [aHR], 0.165; 95% confidence interval [CI], 0.077-0.350; P < 0.001) and
      overall death (vs. untreated; aHR, 0.146; 95% CI, 0.050-0.424; P < 0.001) during
      the median observation of 3.5 (interquartile range, 1.9-6.6) years. The SVR group
      had significantly lower risk of HCC than the untreated group among patients with
      intermediate-probability (n = 492: aHR, 0.171; 95% CI, 0.051-0.578; P = 0.004)
      and high-probability (n = 446: aHR, 0.243; 95% CI, 0.107-0.551; P < 0.001) of
      significant fibrosis. HRs were maintained after balancing with inverse
      probability weighting. SVR was associated with reduced risk of HCC development
      and all-cause mortality in patients with chronic hepatitis C.

PMID- 30209335
TI  - Task-evoked pupil responses reflect internal belief states.
AB  - Perceptual decisions about the state of the environment are often made in the
      face of uncertain evidence. Internal uncertainty signals are considered important
      regulators of learning and decision-making. A growing body of work has implicated
      the brain's arousal systems in uncertainty signaling. Here, we found that two
      specific computational variables, postulated by recent theoretical work, evoke
      boosts of arousal at different times during a perceptual decision: decision
      confidence (the observer's internally estimated probability that a choice was
      correct given the evidence) before feedback, and prediction errors (deviations
      from expected reward) after feedback. We monitored pupil diameter, a peripheral
      marker of central arousal state, while subjects performed a challenging
      perceptual choice task with a delayed monetary reward. We quantified evoked pupil
      responses during decision formation and after reward-linked feedback. During both
      intervals, decision difficulty and accuracy had interacting effects on pupil
      responses. Pupil responses negatively scaled with decision confidence prior to
      feedback and scaled with uncertainty-dependent prediction errors after feedback.
      This pattern of pupil responses during both intervals was in line with a model
      using the observer's graded belief about choice accuracy to anticipate rewards
      and compute prediction errors. We conclude that pupil-linked arousal systems are
      modulated by internal belief states.

PMID- 30209337
TI  - Hypofractionated Stereotactic Radiotherapy for Patients with Intracranial
      Meningiomas: impact of radiotherapy regimen on local control.
AB  - We evaluated efficacy and tolerance of hypofractionated stereotactic radiation
      treatment (hFSRT) in the management of intracranial meningiomas. Between December
      2008 and June 2016, 126 patients with 136 intracranial meningiomas were treated
      with robotic hFSRT. hFSRT was performed as primary irradiation and as a salvage
      option for the local recurrence after prior radiotherapy. The median prescription
      dose was 25 Gy (12-40) with a median number of fractions of 5 (3-10). After a
      median follow-up of 20.3 months (range 1-77 months), the 24-months local control
      (LC) rate was 81% in the primary hFSRT group and 39% after hFSRT in the re
      irradiation group (p=0.002). The clinical control rate of symptoms in the overall
      population was 95% (95% CI: 89-98%). Progression-free survival (PFS) in the
      overall population at 24 months was 70% (95% CI: 60%-79%). In the primary hFSRT
      group, PFS was significantly lower with the most hypofractionated schedules of 21
      23 Gy in 3 fractions vs. 25-40 Gy in 5-10 fractions: 62% vs. 92% (p = 0.0006).
      The incidence of radionecrosis at 24 months was significantly lower in the
      primary hFSRT group, at 2% vs. 20% in the re-irradiation hFSRT group (p = 0.002).

PMID- 30209338
TI  - Differential HDAC1/2 network analysis reveals a role for prefoldin/CCT in HDAC1/2
      complex assembly.
AB  - HDAC1 and HDAC2 are components of several corepressor complexes (NuRD, Sin3,
      CoREST and MiDAC) that regulate transcription by deacetylating histones resulting
      in a more compact chromatin environment. This limits access of transcriptional
      machinery to genes and silences transcription. While using an AP-MS approach to
      map HDAC1/2 protein interaction networks, we noticed that N-terminally tagged
      versions of HDAC1 and HDAC2 did not assemble into HDAC corepressor complexes as
      expected, but instead appeared to be stalled with components of the prefoldin-CCT
      chaperonin pathway. These N-terminally tagged HDACs were also catalytically
      inactive. In contrast to the N-terminally tagged HDACs, C-terminally tagged HDAC1
      and HDAC2 captured complete histone deacetylase complexes and the purified
      proteins had deacetylation activity that could be inhibited by SAHA (Vorinostat),
      a Class I/II HDAC inhibitor. This tag-mediated reprogramming of the HDAC1/2
      protein interaction network suggests a mechanism whereby HDAC1 is first loaded
      into the CCT complex by prefoldin to complete folding, and then assembled into
      active, functional HDAC complexes. Imaging revealed that the prefoldin subunit
      VBP1 colocalises with nuclear HDAC1, suggesting that delivery of HDAC1 to the CCT
      complex happens in the nucleus.

PMID- 30209339
TI  - Antimicrobial promotion of pig growth is associated with tissue-specific
      remodeling of bile acid signature and signaling.
AB  - The spread of bacterial resistance to antimicrobials (AMA) have intensified
      efforts to discontinue the non-therapeutic use of AMA in animal production.
      Finding alternatives to AMA, however, is currently encumbered by the obscure
      mechanism that underlies their growth-promoting action. In this report, we
      demonstrate that combinations of antibiotics and zinc oxide at doses commonly
      used for stimulating growth or preventing post-weaning enteritis in pigs converge
      in promoting microbial production of bile acids (BA) in the intestine. This leads
      to tissue-specific modifications in the proportion of BA, thereby amplifying BA
      signaling in intestine, liver, and white adipose tissue (WAT). Activation of BA
      regulated pathways ultimately reinforces the intestinal protection against
      bacterial infection and pathological secretion of fluids and electrolytes,
      attenuates inflammation in colon and WAT, alters protein and lipid metabolism in
      liver, and increases the circulating levels of the hormone FGF19. Conceivably,
      these alterations could spare nutrients for growth and improve the metabolic
      efficiency of AMA-treated animals. This work provides evidence that BA act as
      signaling molecules that mediate host physiological, metabolic, and immune
      responses to the AMA-induced alterations in gut microbial metabolism, eventually
      permitting the growth-promoting action of AMA. Consequently, BA emerge as a
      promising target for developing efficacious alternatives to AMA.

PMID- 30209340
TI  - The SCO1731 methyltransferase modulates actinorhodin production and morphological
      differentiation of Streptomyces coelicolor A3(2).
AB  - Streptomyces coelicolor is a Gram-positive microorganism often used as a model of
      physiological and morphological differentiation in streptomycetes, prolific
      producers of secondary metabolites with important biological activities. In the
      present study, we analysed Streptomyces coelicolor growth and differentiation in
      the presence of the hypo-methylating agent 5'-aza-2'-deoxycytidine (5-aza-dC) in
      order to investigate whether cytosine methylation has a role in differentiation.
      We found that cytosine demethylation caused a delay in spore germination, aerial
      mycelium development, sporulation, as well as a massive impairment of
      actinorhodin production. Thus, we searched for putative DNA methyltransferase
      genes in the genome and constructed a mutant of the SCO1731 gene. The analysis of
      the SCO1731::Tn5062 mutant strain demonstrated that inactivation of SCO1731 leads
      to a strong decrease of cytosine methylation and almost to the same phenotype
      obtained after 5-aza-dC treatment. Altogether, our data demonstrate that cytosine
      methylation influences morphological differentiation and actinorhodin production
      in S. coelicolor and expand our knowledge on this model bacterial system.

PMID- 30209344
TI  - Temporal dynamics of bacteria-plasmid coevolution under antibiotic selection.
AB  - Horizontally acquired genes can be costly to express even if they encode useful
      traits, such as antibiotic resistance. We previously showed that when selected
      with tetracycline, Escherichia coli carrying the tetracycline-resistance plasmid
      RK2 evolved mutations on both replicons that together provided increased
      tetracycline resistance at reduced cost. Here we investigate the temporal
      dynamics of this intragenomic coevolution. Using genome sequencing we show that
      the order of adaptive mutations was highly repeatable across three independently
      evolving populations. Each population first gained a chromosomal mutation in ompF
      which shortened lag phase and increased tetracycline resistance. This was
      followed by mutations impairing the plasmid-encoded tetracycline efflux pump, and
      finally, additional resistance-associated chromosomal mutations. Thus, reducing
      the cost of the horizontally acquired tetracycline resistance was contingent on
      first evolving a degree of chromosomally encoded resistance. We conclude
      therefore that the trajectory of bacteria-plasmid coevolution was constrained to
      a single repeatable path.

PMID- 30209343
TI  - Stabilization of HIF-2alpha impacts pancreas growth.
AB  - Hypoxia inducible factors (HIFs) are critical regulators of the response to
      oxygen deficiency by activating target genes involved in a variety of biological
      functions. HIFs have been implicated in the pathophysiology of numerous
      pathologies including cancer. Patients with mutations in the von Hippel-Lindau
      (VHL) gene, an essential regulator of HIF activity, develop tumors in several
      organs including the pancreas. Previous functional studies of HIF activation in
      the pancreas have used Vhlh (the murine homolog of VHL) deficient mice. However,
      the role of each specific HIF transcription factors in the pancreas has not been
      thoroughly examined. We derived mice that constitutively express a normoxia
      stable form of HIF2alpha in the pancreas. Activation of HIF2alpha in the pancreas
      severely impairs postnatal exocrine pancreas. Mice with pancreas-specific
      activation of HIF2alpha develop histological features reminiscent of pancreatitis
      including loss of acinar cells, ductal dilation and fibrosis. Moreover, we
      provide evidence that signaling pathways important for acinar cell homeostasis
      are altered in HIF2alpha-overexpressing pancreata.

PMID- 30209342
TI  - Intra-auditory integration between pitch and loudness in humans: Evidence of
      super-optimal integration at moderate uncertainty in auditory signals.
AB  - When a person plays a musical instrument, sound is produced and the integrated
      frequency and intensity produced are perceived aurally. The central nervous
      system (CNS) receives defective afferent signals from auditory systems and
      delivers imperfect efferent signals to the motor system due to the noise in both
      systems. However, it is still little known about auditory-motor interactions for
      successful performance. Here, we investigated auditory-motor interactions as
      multi-sensory input and multi-motor output system. Subjects performed a constant
      force production task using four fingers in three different auditory feedback
      conditions, where either the frequency (F), intensity (I), or both frequency and
      intensity (FI) of an auditory tone changed with sum of finger forces. Four levels
      of uncertainty (high, moderate-high, moderate-low, and low) were conditioned by
      manipulating the feedback gain of the produced force. We observed performance
      enhancement under the FI condition compared to either F or I alone at moderate
      high uncertainty. Interestingly, the performance enhancement was greater than the
      prediction of the Bayesian model, suggesting super-optimality. We also observed
      deteriorated synergistic multi-finger interactions as the level of uncertainty
      increased, suggesting that the CNS responded to increased uncertainty by changing
      control strategy of multi-finger actions.

PMID- 30209341
TI  - The acetylation of cyclin-dependent kinase 5 at lysine 33 regulates kinase
      activity and neurite length in hippocampal neurons.
AB  - Cyclin-dependent kinase 5 (CDK5) plays a pivotal role in neural development and
      neurodegeneration. CDK5 activity can be regulated by posttranslational
      modifications, including phosphorylation and S-nitrosylation. In this study, we
      demonstrate a novel mechanism by which the acetylation of CDK5 at K33 (Ac-CDK5)
      results in the loss of ATP binding and impaired kinase activity. We identify GCN5
      and SIRT1 as critical factor controlling Ac-CDK5 levels. Ac-CDK5 achieved its
      lowest levels in rat fetal brains but was dramatically increased during postnatal
      periods. Intriguingly, nuclear Ac-CDK5 levels negatively correlated with neurite
      length in embryonic hippocampal neurons. Either treatment with the SIRT1
      activator SRT1720 or overexpression of SIRT1 leads to increases in neurite
      length, whereas SIRT1 inhibitor EX527 or ectopic expression of acetyl-mimetic
      (K33Q) CDK5 induced the opposite effect. Furthermore, the expression of nuclear
      targeted CDK5 K33Q abolished the SRT1720-induced neurite outgrowth, showing that
      SIRT1 positively regulates neurite outgrowth via deacetylation of nuclear CDK5.
      The CDK5 activity-dependent increase of neurite length was mediated by enhanced
      transcriptional regulation of BDNF via unknown mechanism(s). Our findings
      identify a novel mechanism by which acetylation-mediated regulation of nuclear
      CDK5 activity plays a critical role in determining neurite length in embryonic
      neurons.

PMID- 30209347
TI  - Natural killer cells and other innate lymphoid cells in cancer.
AB  - Immuno-oncology is an emerging field that has revolutionized cancer treatment.
      Most immunomodulatory strategies focus on enhancing T cell responses, but there
      has been a recent surge of interest in harnessing the relatively underexplored
      natural killer (NK) cell compartment for therapeutic interventions. NK cells show
      cytotoxic activity against diverse tumour cell types, and some of the clinical
      approaches originally developed to increase T cell cytotoxicity may also activate
      NK cells. Moreover, increasing numbers of studies have identified novel methods
      for increasing NK cell antitumour immunity and expanding NK cell populations ex
      vivo, thereby paving the way for a new generation of anticancer immunotherapies.
      The role of other innate lymphoid cells (group 1 innate lymphoid cell (ILC1),
      ILC2 and ILC3 subsets) in tumours is also being actively explored. This Review
      provides an overview of the field and summarizes current immunotherapeutic
      approaches for solid tumours and haematological malignancies.

PMID- 30209346
TI  - Genome-wide DNA methylation analysis of human peripheral blood reveals
      susceptibility loci of diabetes-related hearing loss.
AB  - Diabetes-related hearing loss (DRHL) is a complication of diabetes mellitus that
      is drawing more attention currently. DNA methylation has a critical role in the
      pathogenesis of type 2 diabetes mellitus (T2DM) and its complications. Therefore,
      we investigated the genome-wide DNA methylation of peripheral blood of T2DM
      patients with/without hearing loss in order to explore the susceptibility loci of
      DRHL. Between DRHL group and control group, 113 gene sites were identified to be
      differentially methylated regions (DMRs). Among 38 DMRs with whole samples, the
      classification accuracy is up to 90%. With alignment to T2DM susceptibility genes
      and deafness genes published, KCNJ11 was found to be the only overlapped gene.
      The DNA methylation level of KCNJ11 was associated with stroke (t = 2.595, p <
      0.05), but not with diabetic nephropathy and diabetic retinopathy. The detective
      rate of distortion product otoacoustic emissions (DPOAE) from low to high
      frequencies (0.7-6 kHz) on the right ear was significantly correlated with the
      methylation level of KCNJ11. The auditory brainstem response (ABR) threshold on
      the right ear was also correlated (r = 0.678, p < 0.05). This DNA methylation
      profile indicates the susceptibility loci of DRHL. The potassium metabolism may
      have a critical role in the hearing loss caused by hyperglycemia.

PMID- 30209348
TI  - Making new memories.

PMID- 30209345
TI  - Objective Evaluation of Multiple Sclerosis Lesion Segmentation using a Data
      Management and Processing Infrastructure.
AB  - We present a study of multiple sclerosis segmentation algorithms conducted at the
      international MICCAI 2016 challenge. This challenge was operated using a new open
      science computing infrastructure. This allowed for the automatic and independent
      evaluation of a large range of algorithms in a fair and completely automatic
      manner. This computing infrastructure was used to evaluate thirteen methods of MS
      lesions segmentation, exploring a broad range of state-of-theart algorithms,
      against a high-quality database of 53 MS cases coming from four centers following
      a common definition of the acquisition protocol. Each case was annotated manually
      by an unprecedented number of seven different experts. Results of the challenge
      highlighted that automatic algorithms, including the recent machine learning
      methods (random forests, deep learning, ...), are still trailing human expertise
      on both detection and delineation criteria. In addition, we demonstrate that
      computing a statistically robust consensus of the algorithms performs closer to
      human expertise on one score (segmentation) although still trailing on detection
      scores.

PMID- 30209350
TI  - The girl with Neanderthal and Denisovan parents.

PMID- 30209349
TI  - Generic sofosbuvir-based interferon-free direct acting antiviral agents for
      patients with chronic hepatitis C virus infection: a real-world multicenter
      observational study.
AB  - Real-world data regarding the effectiveness and safety of generic sofosbuvir
      (SOF)-based interferon-free direct acting antiviral agents (DAAs) for patients
      with chronic hepatitis C virus (HCV) infection remain limited. A total of 517
      chronic HCV-infected patients receiving 12 or 24 weeks of SOF-based therapies
      were retrospectively enrolled in 4 academic centers in Taiwan. The rate of
      sustained virologic response at week 12 off-therapy (SVR12) and that of treatment
      completion were assessed. The baseline characteristics and on-treatment HCV viral
      kinetics to predict SVR12 were analyzed. By evaluable population (EP) analysis,
      the SVR12 rate was 95.4% (95% confidence interval [CI]: 93.2-96.9%). The SVR12
      was achieved in 29 of 34 patients (85.3%, 95% CI: 69.6-93.6%), 130 of 139
      patients (93.5%, 95% CI: 88.2-96.6%), 119 of 124 patients (96.0%, 95% CI: 90.9
      98.3%) and 215 of 220 patients (97.7%, 95% CI: 94.8-99.0%) who received SOF in
      combination with ribavirin (RBV), ledipasvir (LDV), daclatasvir (DCV) and
      velpatasvir (VEL), respectively. Of 517 patients, 514 (99.4%) completed the
      scheduled treatment. All 15 patients with true virologic failures were relapsers.
      Two decompensated cirrhotic patients had on-treatment deaths which were not
      related to DAAs. All 7 patients who were lost to follow-up had undetectable HCV
      RNA level at the last visit. The SVR12 rates were comparable in terms of baseline
      patient characteristics and viral decline at week 4 of treatment. In conclusion,
      generic SOF-based regimens are well tolerated and provide high SVR12 rates in
      patients with chronic HCV infection.

PMID- 30209351
TI  - Urinary tract infection is common in VLBW infants.
AB  - OBJECTIVE: Determine the significance of urinary tract infection (UTI) as a cause
      of late onset sepsis (LOS) in very low birth weight (VLBW) infants in the
      Neonatal Intensive Care Unit (NICU). STUDY DESIGN: Analysis of blood,
      cerebrospinal fluid and urine culture results in VLBW infants >72-h old, admitted
      to the Georgetown University Hospital NICU between 2005 and 2015. RESULT: Of 527
      VLBW infants, 297 (56.4%) underwent 911 evaluations for LOS; only one-third
      included urine cultures. UTI was diagnosed in 8.5% of VLBW infants (range 2
      15.9%) and in 13.8% of infants weighing < 1000 g at birth. Gram-negative
      infections predominated. Concomitant blood cultures were negative in 96% of
      infants. UTI was more common than bloodstream infection by 2015. CONCLUSION: UTI
      is a significant cause of infection in VLBW infants. Urine culture should be
      included in all LOS evaluations in order to facilitate accurate diagnosis and
      appropriate antibiotic therapy.

PMID- 30209353
TI  - Curcumin alleviates postprandial glycaemic response in healthy subjects: A cross
      over, randomized controlled study.
AB  - In the current study, we aimed to evaluate the effects of a single dose of
      curcumin and/or fish oil on postprandial glycaemic parameters in healthy
      individuals. This was a randomised, placebo-controlled and crossover study.
      Sixteen (n = 16) volunteers were randomised to receive placebo, curcumin (180 mg)
      tablets, fish oil (1.2 g long chain omega-3 polyunsaturated fatty acids) capsules
      and curcumin + fish oil prior to a standard meal on 4 test days separated by a
      week. Blood glucose, serum insulin and triglycerides were measured at intervals
      between 0-120 min. Difference between the treatments was measured using two-way
      repeated measures analysis of variance and pair-wise comparisons using Wilcoxon
      signed-rank or paired t-test as appropriate. Postprandial glucose concentrations
      were significantly lower in the curcumin (60.6%, P = 0.0007) and curcumin +
      fishoil group (51%, P = 0.002) groups at 60 min from baseline. Compared with
      placebo, area under the curve (AUC) for change in blood glucose concentration was
      reduced by curcumin (36%, P = 0.003) and curcumin + fishoil (30%, 0.004), but not
      fish oil alone (p = 0.105). Both curcumin (P = 0.01) and curcumin + fishoil (P =
      0.03) treatments significantly lowered postprandial insulin (AUC) by 26% in
      comparison with placebo. Curcumin, but not fish oil, reduces postprandial
      glycaemic response and insulin demand for glucose control.

PMID- 30209352
TI  - A post-ingestive amino acid sensor promotes food consumption in Drosophila.
AB  - Adequate protein intake is crucial for the survival and well-being of animals.
      How animals assess prospective protein sources and ensure dietary amino acid
      intake plays a critical role in protein homeostasis. By using a quantitative
      feeding assay, we show that three amino acids, L-glutamate (L-Glu), L-alanine (L
      Ala) and L-aspartate (L-Asp), but not their D-enantiomers or the other 17 natural
      L-amino acids combined, rapidly promote food consumption in the fruit fly
      Drosophila melanogaster. This feeding-promoting effect of dietary amino acids is
      independent of mating experience and internal nutritional status. In vivo and ex
      vivo calcium imagings show that six brain neurons expressing diuretic hormone 44
      (DH44) can be rapidly and directly activated by these amino acids, suggesting
      that these neurons are an amino acid sensor. Genetic inactivation of DH44+
      neurons abolishes the increase in food consumption induced by dietary amino
      acids, whereas genetic activation of these neurons is sufficient to promote
      feeding, suggesting that DH44+ neurons mediate the effect of dietary amino acids
      to promote food consumption. Single-cell transcriptome analysis and
      immunostaining reveal that a putative amino acid transporter, CG13248, is
      enriched in DH44+ neurons. Knocking down CG13248 expression in DH44+ neurons
      blocks the increase in food consumption and eliminates calcium responses induced
      by dietary amino acids. Therefore, these data identify DH44+ neuron as a key
      sensor to detect amino acids and to enhance food intake via a putative
      transporter CG13248. These results shed critical light on the regulation of
      protein homeostasis at organismal levels by the nervous system.

PMID- 30209355
TI  - Nanoimmunotherapy to treat ischaemic heart disease.
AB  - Atherosclerosis is a chronic disease of the large arteries and the underlying
      cause of myocardial infarction and stroke. Atherosclerosis is driven by
      cholesterol accumulation and subsequent inflammation in the vessel wall. Despite
      the clinical successes of lipid-lowering treatments, atherosclerosis remains one
      of the major threats to human health worldwide. Over the past 20 years, insights
      into cardiovascular immunopathology have provided a plethora of new potential
      therapeutic targets to reduce the risk of atherosclerosis and have shifted the
      therapeutic focus from lipids to inflammation. In 2017, the CANTOS trial
      demonstrated for the first time the beneficial effects of targeting inflammation
      to treat cardiovascular disease by showing that IL-1beta inhibition can reduce
      the recurrence rate of cardiovascular events in a large cohort of patients. At
      the same time, preclinical studies have highlighted nanotechnology approaches
      that facilitate the specific targeting of innate immune cells, which could
      potentially generate more effective immunomodulatory treatments to induce disease
      regression and prevent the recurrence of cardiovascular events. The clinical
      translation of such nanoimmunotherapies and their application to treat patients
      with ischaemic heart disease are challenges that lie ahead.

PMID- 30209354
TI  - Using reconditioned pacemakers to treat bradycardia in Africa.

PMID- 30209356
TI  - Alterations of blood pulsations parameters in carotid basin due to body position
      change.
AB  - The velocity of the pulse wave (PWV) propagating through the vascular tree is an
      essential parameter for diagnostic the state of the cardiovascular system
      especially when it is measured in the pool of carotid arteries. In this research,
      we showed for the first time that the time of the blood-pressure-wave propagation
      from the heart to the face is a function of the body position. Significant
      asymmetry and asynchronicity of blood pulsations in the facial area were found in
      a recumbent position. Parameters of blood pulsations were measured by an advanced
      camera-based photoplethysmography system in 73 apparently healthy subjects. Most
      likely, observed changes of the blood-pulsation parameters are caused by
      variations of the arterial blood pressure due to hydrostatic pressure changes,
      and secondary reaction of blood vessels in response to these variations.
      Demonstrated feasibility of PWV measurements in the pool of carotid arteries
      provides considerable advantages over other technologies. Moreover, possibilities
      of the method to estimate physiological regulation of the peripheral blood flow
      (particularly, as a response to the gravitational changes) have been
      demonstrated. The proposed concept allows development of non-invasive medical
      equipment capable of solving a wide range of scientific and practical problems
      related to vascular physiology.

PMID- 30209358
TI  - Sweet success for ccRCC isotope tracing.

PMID- 30209359
TI  - Targeting methylation.

PMID- 30209357
TI  - Actinobacteria associated with Glycyrrhiza inflata Bat. are diverse and have
      plant growth promoting and antimicrobial activity.
AB  - Many of the plant associated microbes may directly and indirectly contribute to
      plant growth and stress resistance. Our aim was to assess the plant growth
      promoting and antimicrobial activities of actinobacteria isolated from
      Glycyrrhiza inflata Bat. plants to find strains that could be applied in
      agricultural industry, for example in reclaiming saline soils. We isolated 36 and
      52 strains that showed morphological characteristics of actinobacteria from one
      year old and three year old G. inflata plants, respectively. Based on 16S rRNA
      gene sequence analysis, the strains represented ten actinobacterial genera. Most
      of the strains had plant growth promoting characteristics in vitro, tolerated 200
      mM NaCl and inhibited the growth of at least one indicator organism. The eight
      selected Streptomyces strains increased the germination rate of G. inflata seeds
      under salt stress. In addition, the four best seed germination promoters promoted
      the growth of G. inflata in vivo. The best promoters of G. inflata growth,
      strains SCAU5283 and SCAU5215, inhibited a wide range of indicator organisms, and
      may thus be considered as promising candidates to be applied in inoculating G.
      inflata.

PMID- 30209360
TI  - A child's walk through nature inspires a research career.

PMID- 30209361
TI  - Europe's renewable energy directive poised to harm global forests.
AB  - This comment raises concerns regarding the way in which a new European directive,
      aimed at reaching higher renewable energy targets, treats wood harvested directly
      for bioenergy use as a carbon-free fuel. The result could consume quantities of
      wood equal to all Europe's wood harvests, greatly increase carbon in the air for
      decades, and set a dangerous global example.

PMID- 30209362
TI  - OCT4B mediates hypoxia-induced cancer dissemination.
AB  - Hypoxia, the reduction of oxygen levels in cells or tissues, elicits a set of
      genes to adjust physiological and pathological demands during normal development
      and cancer progression. OCT4, a homeobox transcription factor, is essential for
      self-renewal of embryonic stem cells, but little is known about the role of OCT4
      in non-germ-cell tumorigenesis. Here, we report that hypoxia stimulates a short
      isoform of OCT4, called OCT4B, via a HIF2alpha-dependent pathway to induce the
      epithelial-mesenchymal transition (EMT) and facilitate cancer dissemination.
      OCT4B overexpression decreased epithelial barrier properties, which led to an
      increase in cell migration and invasion in lung cancer cells. OCT4B knockdown
      attenuated HIF2alpha-induced EMT and inhibited cancer dissemination in cell-line
      and animal models. We observed that OCT4B bound the SLUG promoter and enhanced
      its expression, and SLUG silencing inhibited OCT4B-mediated EMT, accompanied with
      decreased cell migration and invasion. Correlation analysis revealed that OCT4B
      expression was significantly associated with the SLUG level in lung tumors. These
      results provide novel insights into OCT4B-mediated oncogenesis in cancer
      dissemination.

PMID- 30209363
TI  - Phosphodiesterase 7B/microRNA-200c relationship regulates triple-negative breast
      cancer cell growth.
AB  - Members of microRNA-200 (miRNA-200) family have a regulatory role in epithelial
      to mesenchymal transition (EMT) by suppressing Zeb1 and Zeb2 expression.
      Consistent with its role in suppressing EMT, Hsa-miR-200c-3p (miR-200c), a member
      of miR-200 family is poorly expressed in mesenchymal-like triple-negative breast
      cancer (TNBC) cells and ectopic miR-200c expression suppresses cell migration. In
      this study, we demonstrated that miR-200c potently inhibited TNBC cell growth and
      tumor development in a mechanism distinct from its ability to downregulate Zeb1
      and Zeb2 expression, because silencing them only marginally affected TNBC cell
      growth. We identified phosphodiesterase 7B (PDE7B) as a bona fide miR-200c
      target. Importantly, miR-200c-led inhibition in cell growth and tumor development
      was prevented by forcing PDE7B transgene expression, while knockdown of PDE7B
      effectively inhibited cell growth. These results suggest that miR-200c inhibits
      cell growth by targeting PDE7B mRNA. To elucidate mechanism underlying miR
      200c/PDE7B regulation of TNBC cell growth, we showed that cAMP concentration was
      lower in TNBC cells compared with estrogen receptor-positive (ER + ) cells, and
      that both miR-200c and PDE7B siRNAs were able to increase cAMP concentration in
      TNBC cells. High level of cellular cAMP has been shown to induce cell cycle
      arrest and apoptosis in TNBC cells. Our observation that ectopic expression of
      miR-200c triggered apoptosis indicates that it does so by elevating level of
      cellular cAMP. Analysis of breast tumor gene expression datasets revealed an
      inverse association between miR-200c and PDE7B expression. Especially, both low
      miR-200c and high PDE7B expression were correlated with poor survival of breast
      cancer patients. Our study supports a critical role of miR-200c/PDE7B
      relationship in TNBC tumorigenesis.

PMID- 30209364
TI  - Does the galaxy NGC1052-DF2 falsify Milgromian dynamics?

PMID- 30209365
TI  - Sensing with tools extends somatosensory processing beyond the body.
AB  - The ability to extend sensory information processing beyond the nervous system1
      has been observed throughout the animal kingdom; for example, when rodents
      palpate objects using whiskers2 and spiders localize prey using webs3. We
      investigated whether the ability to sense objects with tools4-9 represents an
      analogous information processing scheme in humans. Here we provide evidence from
      behavioural psychophysics, structural mechanics and neuronal modelling, which
      shows that tools are treated by the nervous system as sensory extensions of the
      body rather than as simple distal links between the hand and the
      environment10,11. We first demonstrate that tool users can accurately sense where
      an object contacts a wooden rod, just as is possible on the skin. We next
      demonstrate that the impact location is encoded by the modal response of the tool
      upon impact, reflecting a pre-neuronal stage of mechanical information processing
      akin to sensing with whiskers2 and webs3. Lastly, we use a computational model of
      tactile afferents12 to demonstrate that impact location can be rapidly re-encoded
      into a temporally precise spiking code. This code predicts the behaviour of human
      participants, providing evidence that the information encoded in motifs shapes
      localization. Thus, we show that this sensory capability emerges from the
      functional coupling between the material, biomechanical and neural levels of
      information processing13,14.

PMID- 30209366
TI  - GAPDH inhibits intracellular pathways during starvation for cellular energy
      homeostasis.
AB  - Starvation poses a fundamental challenge to cell survival. Whereas the role of
      autophagy in promoting energy homeostasis in this setting has been extensively
      characterized1, other mechanisms are less well understood. Here we reveal that
      glyceraldehyde 3-phosphate dehydrogenase (GAPDH) inhibits coat protein I (COPI)
      transport by targeting a GTPase-activating protein (GAP) towards ADP-ribosylation
      factor 1 (ARF1) to suppress COPI vesicle fission. GAPDH inhibits multiple other
      transport pathways, also by targeting ARF GAPs. Further characterization suggests
      that this broad inhibition is activated by the cell during starvation to reduce
      energy consumption. These findings reveal a remarkable level of coordination
      among the intracellular transport pathways that underlies a critical mechanism of
      cellular energy homeostasis.

PMID- 30209367
TI  - Optimized arylomycins are a new class of Gram-negative antibiotics.
AB  - Multidrug-resistant bacteria are spreading at alarming rates, and despite
      extensive efforts no new class of antibiotic with activity against Gram-negative
      bacteria has been approved in over fifty years. Natural products and their
      derivatives have a key role in combating Gram-negative pathogens. Here we report
      chemical optimization of the arylomycins-a class of natural products with weak
      activity and limited spectrum-to obtain G0775, a molecule with potent, broad
      spectrum activity against Gram-negative bacteria. G0775 inhibits the essential
      bacterial type I signal peptidase, a new antibiotic target, through an
      unprecedented molecular mechanism. It circumvents existing antibiotic resistance
      mechanisms and retains activity against contemporary multidrug-resistant Gram
      negative clinical isolates in vitro and in several in vivo infection models.
      These findings demonstrate that optimized arylomycin analogues such as G0775
      could translate into new therapies to address the growing threat of multidrug
      resistant Gram-negative infections.

PMID- 30209368
TI  - Future response of global coastal wetlands to sea-level rise.
AB  - The response of coastal wetlands to sea-level rise during the twenty-first
      century remains uncertain. Global-scale projections suggest that between 20 and
      90 per cent (for low and high sea-level rise scenarios, respectively) of the
      present-day coastal wetland area will be lost, which will in turn result in the
      loss of biodiversity and highly valued ecosystem services1-3. These projections
      do not necessarily take into account all essential geomorphological4-7 and socio
      economic system feedbacks8. Here we present an integrated global modelling
      approach that considers both the ability of coastal wetlands to build up
      vertically by sediment accretion, and the accommodation space, namely, the
      vertical and lateral space available for fine sediments to accumulate and be
      colonized by wetland vegetation. We use this approach to assess global-scale
      changes in coastal wetland area in response to global sea-level rise and
      anthropogenic coastal occupation during the twenty-first century. On the basis of
      our simulations, we find that, globally, rather than losses, wetland gains of up
      to 60 per cent of the current area are possible, if more than 37 per cent (our
      upper estimate for current accommodation space) of coastal wetlands have
      sufficient accommodation space, and sediment supply remains at present levels. In
      contrast to previous studies1-3, we project that until 2100, the loss of global
      coastal wetland area will range between 0 and 30 per cent, assuming no further
      accommodation space in addition to current levels. Our simulations suggest that
      the resilience of global wetlands is primarily driven by the availability of
      accommodation space, which is strongly influenced by the building of
      anthropogenic infrastructure in the coastal zone and such infrastructure is
      expected to change over the twenty-first century. Rather than being an inevitable
      consequence of global sea-level rise, our findings indicate that large-scale loss
      of coastal wetlands might be avoidable, if sufficient additional accommodation
      space can be created through careful nature-based adaptation solutions to coastal
      management.

PMID- 30209369
TI  - Autogenous and efficient acceleration of energetic ions upstream of Earth's bow
      shock.
AB  - Earth and its magnetosphere are immersed in the supersonic flow of the solar-wind
      plasma that fills interplanetary space. As the solar wind slows and deflects to
      flow around Earth, or any other obstacle, a 'bow shock' forms within the flow.
      Under almost all solar-wind conditions, planetary bow shocks such as Earth's are
      collisionless, supercritical shocks, meaning that they reflect and accelerate a
      fraction of the incident solar-wind ions as an energy dissipation mechanism1,2,
      which results in the formation of a region called the ion foreshock3. In the
      foreshock, large-scale, transient phenomena can develop, such as 'hot flow
      anomalies'4-9, which are concentrations of shock-reflected, suprathermal ions
      that are channelled and accumulated along certain structures in the upstream
      magnetic field. Hot flow anomalies evolve explosively, often resulting in the
      formation of new shocks along their upstream edges5,10, and potentially
      contribute to particle acceleration11-13, but there have hitherto been no
      observations to constrain this acceleration or to confirm the underlying
      mechanism. Here we report observations of a hot flow anomaly accelerating solar
      wind ions from roughly 1-10 kiloelectronvolts up to almost 1,000
      kiloelectronvolts. The acceleration mechanism depends on the mass and charge
      state of the ions and is consistent with first-order Fermi acceleration14,15. The
      acceleration that we observe results from only the interaction of Earth's bow
      shock with the solar wind, but produces a much, much larger number of energetic
      particles compared to what would typically be produced in the foreshock from
      acceleration at the bow shock. Such autogenous and efficient acceleration at
      quasi-parallel bow shocks (the normal direction of which are within about 45
      degrees of the interplanetary magnetic field direction) provides a potential
      solution to Fermi's 'injection problem', which requires an as-yet-unexplained
      seed population of energetic particles, and implies that foreshock transients may
      be important in the generation of cosmic rays at astrophysical shocks throughout
      the cosmos.

PMID- 30209371
TI  - Three-dimensional printing of hierarchical liquid-crystal-polymer structures.
AB  - Fibre-reinforced polymer structures are often used when stiff lightweight
      materials are required, such as in aircraft, vehicles and biomedical implants.
      Despite their very high stiffness and strength1, such lightweight materials
      require energy- and labour-intensive fabrication processes2, exhibit typically
      brittle fracture and are difficult to shape and recycle3,4. This is in stark
      contrast to lightweight biological materials such as bone, silk and wood, which
      form by directed self-assembly into complex, hierarchically structured shapes
      with outstanding mechanical properties5-11, and are circularly integrated into
      the environment. Here we demonstrate a three-dimensional (3D) printing approach
      to generate recyclable lightweight structures with hierarchical architectures,
      complex geometries and unprecedented stiffness and toughness. Their features
      arise from the self-assembly of liquid-crystal polymer molecules into highly
      oriented domains during extrusion of the molten feedstock material. By orienting
      the molecular domains with the print path, we are able to reinforce the polymer
      structure according to the expected mechanical stresses, leading to stiffness,
      strength and toughness that outperform state-of-the-art 3D-printed polymers by an
      order of magnitude and are comparable with the highest-performance lightweight
      composites1,12. The ability to combine the top-down shaping freedom of 3D
      printing with bottom-up molecular control over polymer orientation opens up the
      possibility to freely design and realize structures without the typical
      restrictions of current manufacturing processes.

PMID- 30209373
TI  - The self-made women who created the Myers-Briggs.

PMID- 30209370
TI  - Tunable long-distance spin transport in a crystalline antiferromagnetic iron
      oxide.
AB  - Spintronics relies on the transport of spins, the intrinsic angular momentum of
      electrons, as an alternative to the transport of electron charge as in
      conventional electronics. The long-term goal of spintronics research is to
      develop spin-based, low-dissipation computing-technology devices. Recently, long
      distance transport of a spin current was demonstrated across ferromagnetic
      insulators1. However, antiferromagnetically ordered materials, the most common
      class of magnetic materials, have several crucial advantages over ferromagnetic
      systems for spintronics applications2: antiferromagnets have no net magnetic
      moment, making them stable and impervious to external fields, and can be operated
      at terahertz-scale frequencies3. Although the properties of antiferromagnets are
      desirable for spin transport4-7, indirect observations of such transport indicate
      that spin transmission through antiferromagnets is limited to only a few
      nanometres8-10. Here we demonstrate long-distance propagation of spin currents
      through a single crystal of the antiferromagnetic insulator haematite (alpha
      Fe2O3)11, the most common antiferromagnetic iron oxide, by exploiting the spin
      Hall effect for spin injection. We control the flow of spin current across a
      haematite-platinum interface-at which spins accumulate, generating the spin
      current-by tuning the antiferromagnetic resonance frequency using an external
      magnetic field12. We find that this simple antiferromagnetic insulator conveys
      spin information parallel to the antiferromagnetic Neel order over distances of
      more than tens of micrometres. This mechanism transports spins as efficiently as
      the most promising complex ferromagnets1. Our results pave the way to
      electrically tunable, ultrafast, low-power, antiferromagnetic-insulator-based
      spin-logic devices6,13 that operate without magnetic fields at room temperature.

PMID- 30209374
TI  - Why you need an agenda for meetings with your principal investigator.

PMID- 30209375
TI  - Future of tidal wetlands depends on coastal management.

PMID- 30209377
TI  - Spins travel far in an antiferromagnet.

PMID- 30209376
TI  - Help graduate students to become good peer reviewers.

PMID- 30209378
TI  - Calling time on New Zealand's oldest tree species.

PMID- 30209379
TI  - Pedagogy helps to prepare undergraduates for the research lab.

PMID- 30209380
TI  - Attributing extreme weather to climate change is not a done deal.

PMID- 30209381
TI  - How Earth-observation scientists are weathering budget cuts and political
      scepticism.

PMID- 30209382
TI  - Celebrate the mathematics of Emmy Noether.

PMID- 30209383
TI  - How to stop data centres from gobbling up the world's electricity.

PMID- 30209384
TI  - Thousands of scientists publish a paper every five days.

PMID- 30209385
TI  - The earliest known drawing in history sends a message through 73,000 years.

PMID- 30209386
TI  - Election security, CRISPR patents and Australia's drought.

PMID- 30209388
TI  - Commentary: Bench to bedside-one step closer?

PMID- 30209387
TI  - Comprehensive state-of-the-art overview of neonatologist performed
      echocardiography: Steps towards standardization of the use of echocardiography in
      neonatal intensive care.

PMID- 30209389
TI  - STAT3-coordinated migration facilitates the dissemination of diffuse large B-cell
      lymphomas.
AB  - The motile characteristics and mechanisms that drive the dissemination of diffuse
      large B-cell lymphoma (DLBCL) are elusive. Here, we show that DLBCL initiates
      dissemination through activating STAT3-mediated amoeboid migration.
      Mechanistically, STAT3 activates RHOH transcription, which competes with the
      RhoGDP dissociation inhibitor RhoGDIgamma to activate RhoA. In addition,
      activated STAT3 regulates microtubule dynamics and releases ARHGEF2 to activate
      RhoA. Both the JAK inhibitor ruxolitinib and the microtubule stabilizer Taxol
      suppress DLBCL cell dissemination in vivo. A clinical DLBCL sample analysis shows
      that STAT3-driven amoeboid movement is particularly important for the transition
      from stage I to stage II. This study elucidates the mechanism of DLBCL
      dissemination and progression and highlights the potential of combating advanced
      DLBCL with a JAK/STAT inhibitor or microtubule stabilizer to reduce DLBCL
      motility; these findings may have a great impact on the development of patient
      tailored treatments for DLBCL.

PMID- 30209390
TI  - In vivo CRISPR editing with no detectable genome-wide off-target mutations.
AB  - CRISPR-Cas genome-editing nucleases hold substantial promise for developing human
      therapeutic applications1-6 but identifying unwanted off-target mutations is
      important for clinical translation7. A well-validated method that can reliably
      identify off-targets in vivo has not been described to date, which means it is
      currently unclear whether and how frequently these mutations occur. Here we
      describe 'verification of in vivo off-targets' (VIVO), a highly sensitive
      strategy that can robustly identify the genome-wide off-target effects of CRISPR
      Cas nucleases in vivo. We use VIVO and a guide RNA deliberately designed to be
      promiscuous to show that CRISPR-Cas nucleases can induce substantial off-target
      mutations in mouse livers in vivo. More importantly, we also use VIVO to show
      that appropriately designed guide RNAs can direct efficient in vivo editing in
      mouse livers with no detectable off-target mutations. VIVO provides a general
      strategy for defining and quantifying the off-target effects of gene-editing
      nucleases in whole organisms, thereby providing a blueprint to foster the
      development of therapeutic strategies that use in vivo gene editing.

PMID- 30209391
TI  - A flavin-based extracellular electron transfer mechanism in diverse Gram-positive
      bacteria.
AB  - Extracellular electron transfer (EET) describes microbial bioelectrochemical
      processes in which electrons are transferred from the cytosol to the exterior of
      the cell1. Mineral-respiring bacteria use elaborate haem-based electron transfer
      mechanisms2-4 but the existence and mechanistic basis of other EETs remain
      largely unknown. Here we show that the food-borne pathogen Listeria monocytogenes
      uses a distinctive flavin-based EET mechanism to deliver electrons to iron or an
      electrode. By performing a forward genetic screen to identify L. monocytogenes
      mutants with diminished extracellular ferric iron reductase activity, we
      identified an eight-gene locus that is responsible for EET. This locus encodes a
      specialized NADH dehydrogenase that segregates EET from aerobic respiration by
      channelling electrons to a discrete membrane-localized quinone pool. Other
      proteins facilitate the assembly of an abundant extracellular flavoprotein that,
      in conjunction with free-molecule flavin shuttles, mediates electron transfer to
      extracellular acceptors. This system thus establishes a simple electron conduit
      that is compatible with the single-membrane structure of the Gram-positive cell.
      Activation of EET supports growth on non-fermentable carbon sources, and an EET
      mutant exhibited a competitive defect within the mouse gastrointestinal tract.
      Orthologues of the genes responsible for EET are present in hundreds of species
      across the Firmicutes phylum, including multiple pathogens and commensal members
      of the intestinal microbiota, and correlate with EET activity in assayed strains.
      These findings suggest a greater prevalence of EET-based growth capabilities and
      establish a previously underappreciated relevance for electrogenic bacteria
      across diverse environments, including host-associated microbial communities and
      infectious disease.

PMID- 30209394
TI  - An abstract drawing from the 73,000-year-old levels at Blombos Cave, South
      Africa.
AB  - Depictive and abstract representations produced by drawing-known from Europe,
      Africa and Southeast Asia after 40,000 years ago-are a prime indicator of modern
      cognition and behaviour1. Here we report a cross-hatched pattern drawn with an
      ochre crayon on a ground silcrete flake recovered from approximately 73,000-year
      old Middle Stone Age levels at Blombos Cave, South Africa. Our microscopic and
      chemical analyses of the pattern confirm that red ochre pigment was intentionally
      applied to the flake with an ochre crayon. The object comes from a level
      associated with stone tools of the Still Bay techno-complex that has previously
      yielded shell beads, cross-hatched engravings on ochre pieces and a variety of
      innovative technologies2-5. This notable discovery pre-dates the earliest
      previously known abstract and figurative drawings by at least 30,000 years. This
      drawing demonstrates the ability of early Homo sapiens in southern Africa to
      produce graphic designs on various media using different techniques.

PMID- 30209393
TI  - De novo design of a fluorescence-activating beta-barrel.
AB  - The regular arrangements of beta-strands around a central axis in beta-barrels
      and of alpha-helices in coiled coils contrast with the irregular tertiary
      structures of most globular proteins, and have fascinated structural biologists
      since they were first discovered. Simple parametric models have been used to
      design a wide range of alpha-helical coiled-coil structures, but to date there
      has been no success with beta-barrels. Here we show that accurate de novo design
      of beta-barrels requires considerable symmetry-breaking to achieve continuous
      hydrogen-bond connectivity and eliminate backbone strain. We then build ensembles
      of beta-barrel backbone models with cavity shapes that match the fluorogenic
      compound DFHBI, and use a hierarchical grid-based search method to simultaneously
      optimize the rigid-body placement of DFHBI in these cavities and the identities
      of the surrounding amino acids to achieve high shape and chemical
      complementarity. The designs have high structural accuracy and bind and
      fluorescently activate DFHBI in vitro and in Escherichia coli, yeast and
      mammalian cells. This de novo design of small-molecule binding activity, using
      backbones custom-built to bind the ligand, should enable the design of
      increasingly sophisticated ligand-binding proteins, sensors and catalysts that
      are not limited by the backbone geometries available in known protein structures.

PMID- 30209392
TI  - The genetic basis and cell of origin of mixed phenotype acute leukaemia.
AB  - Mixed phenotype acute leukaemia (MPAL) is a high-risk subtype of leukaemia with
      myeloid and lymphoid features, limited genetic characterization, and a lack of
      consensus regarding appropriate therapy. Here we show that the two principal
      subtypes of MPAL, T/myeloid (T/M) and B/myeloid (B/M), are genetically distinct.
      Rearrangement of ZNF384 is common in B/M MPAL, and biallelic WT1 alterations are
      common in T/M MPAL, which shares genomic features with early T-cell precursor
      acute lymphoblastic leukaemia. We show that the intratumoral immunophenotypic
      heterogeneity characteristic of MPAL is independent of somatic genetic variation,
      that founding lesions arise in primitive haematopoietic progenitors, and that
      individual phenotypic subpopulations can reconstitute the immunophenotypic
      diversity in vivo. These findings indicate that the cell of origin and founding
      lesions, rather than an accumulation of distinct genomic alterations, prime
      tumour cells for lineage promiscuity. Moreover, these findings position MPAL in
      the spectrum of immature leukaemias and provide a genetically informed framework
      for future clinical trials of potential treatments for MPAL.

PMID- 30209395
TI  - Touch and tactile neuropathic pain sensitivity are set by corticospinal
      projections.
AB  - Current models of somatosensory perception emphasize transmission from primary
      sensory neurons to the spinal cord and on to the brain1-4. Mental influence on
      perception is largely assumed to occur locally within the brain. Here we
      investigate whether sensory inflow through the spinal cord undergoes direct top
      down control by the cortex. Although the corticospinal tract (CST) is
      traditionally viewed as a primary motor pathway5, a subset of corticospinal
      neurons (CSNs) originating in the primary and secondary somatosensory cortex
      directly innervate the spinal dorsal horn via CST axons. Either reduction in
      somatosensory CSN activity or transection of the CST in mice selectively impairs
      behavioural responses to light touch without altering responses to noxious
      stimuli. Moreover, such CSN manipulation greatly attenuates tactile allodynia in
      a model of peripheral neuropathic pain. Tactile stimulation activates
      somatosensory CSNs, and their corticospinal projections facilitate light-touch
      evoked activity of cholecystokinin interneurons in the deep dorsal horn. This
      touch-driven feed-forward spinal-cortical-spinal sensitization loop is important
      for the recruitment of spinal nociceptive neurons under tactile allodynia. These
      results reveal direct cortical modulation of normal and pathological tactile
      sensory processing in the spinal cord and open up opportunities for new
      treatments for neuropathic pain.

PMID- 30209396
TI  - A cortical filter that learns to suppress the acoustic consequences of movement.
AB  - Sounds can arise from the environment and also predictably from many of our own
      movements, such as vocalizing, walking, or playing music. The capacity to
      anticipate these movement-related (reafferent) sounds and distinguish them from
      environmental sounds is essential for normal hearing1,2, but the neural circuits
      that learn to anticipate the often arbitrary and changeable sounds that result
      from our movements remain largely unknown. Here we developed an acoustic virtual
      reality (aVR) system in which a mouse learned to associate a novel sound with its
      locomotor movements, allowing us to identify the neural circuit mechanisms that
      learn to suppress reafferent sounds and to probe the behavioural consequences of
      this predictable sensorimotor experience. We found that aVR experience gradually
      and selectively suppressed auditory cortical responses to the reafferent
      frequency, in part by strengthening motor cortical activation of auditory
      cortical inhibitory neurons that respond to the reafferent tone. This plasticity
      is behaviourally adaptive, as aVR-experienced mice showed an enhanced ability to
      detect non-reafferent tones during movement. Together, these findings describe a
      dynamic sensory filter that involves motor cortical inputs to the auditory cortex
      that can be shaped by experience to selectively suppress the predictable acoustic
      consequences of movement.

PMID- 30209397
TI  - Necroptosis microenvironment directs lineage commitment in liver cancer.
AB  - Primary liver cancer represents a major health problem. It comprises
      hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), which
      differ markedly with regards to their morphology, metastatic potential and
      responses to therapy. However, the regulatory molecules and tissue context that
      commit transformed hepatic cells towards HCC or ICC are largely unknown. Here we
      show that the hepatic microenvironment epigenetically shapes lineage commitment
      in mosaic mouse models of liver tumorigenesis. Whereas a necroptosis-associated
      hepatic cytokine microenvironment determines ICC outgrowth from oncogenically
      transformed hepatocytes, hepatocytes containing identical oncogenic drivers give
      rise to HCC if they are surrounded by apoptotic hepatocytes. Epigenome and
      transcriptome profiling of mouse HCC and ICC singled out Tbx3 and Prdm5 as major
      microenvironment-dependent and epigenetically regulated lineage-commitment
      factors, a function that is conserved in humans. Together, our results provide
      insight into lineage commitment in liver tumorigenesis, and explain molecularly
      why common liver-damaging risk factors can lead to either HCC or ICC.

PMID- 30209398
TI  - Giant and anisotropic many-body spin-orbit tunability in a strongly correlated
      kagome magnet.
AB  - Owing to the unusual geometry of kagome lattices-lattices made of corner-sharing
      triangles-their electrons are useful for studying the physics of frustrated,
      correlated and topological quantum electronic states1-9. In the presence of
      strong spin-orbit coupling, the magnetic and electronic structures of kagome
      lattices are further entangled, which can lead to hitherto unknown spin-orbit
      phenomena. Here we use a combination of vector-magnetic-field capability and
      scanning tunnelling microscopy to elucidate the spin-orbit nature of the kagome
      ferromagnet Fe3Sn2 and explore the associated exotic correlated phenomena. We
      discover that a many-body electronic state from the kagome lattice couples
      strongly to the vector field with three-dimensional anisotropy, exhibiting a
      magnetization-driven giant nematic (two-fold-symmetric) energy shift. Probing the
      fermionic quasi-particle interference reveals consistent spontaneous nematicity-a
      clear indication of electron correlation-and vector magnetization is capable of
      altering this state, thus controlling the many-body electronic symmetry. These
      spin-driven giant electronic responses go well beyond Zeeman physics and point to
      the realization of an underlying correlated magnetic topological phase. The
      tunability of this kagome magnet reveals a strong interplay between an externally
      applied field, electronic excitations and nematicity, providing new ways of
      controlling spin-orbit properties and exploring emergent phenomena in topological
      or quantum materials10-12.

PMID- 30209399
TI  - Accurate classification of BRCA1 variants with saturation genome editing.
AB  - Variants of uncertain significance fundamentally limit the clinical utility of
      genetic information. The challenge they pose is epitomized by BRCA1, a tumour
      suppressor gene in which germline loss-of-function variants predispose women to
      breast and ovarian cancer. Although BRCA1 has been sequenced in millions of
      women, the risk associated with most newly observed variants cannot be
      definitively assigned. Here we use saturation genome editing to assay 96.5% of
      all possible single-nucleotide variants (SNVs) in 13 exons that encode
      functionally critical domains of BRCA1. Functional effects for nearly 4,000 SNVs
      are bimodally distributed and almost perfectly concordant with established
      assessments of pathogenicity. Over 400 non-functional missense SNVs are
      identified, as well as around 300 SNVs that disrupt expression. We predict that
      these results will be immediately useful for the clinical interpretation of BRCA1
      variants, and that this approach can be extended to overcome the challenge of
      variants of uncertain significance in additional clinically actionable genes.

PMID- 30209401
TI  - Author Correction: Enhancer decommissioning by LSD1 during embryonic stem cell
      differentiation.
AB  - In this Letter, the western blot for LSD1 in the right panel of Fig. 2b ('TCP +')
      was inadvertently duplicated from the tubulin blot immediately below. The actual
      tubulin western blot shows the same result, with no significant change to the
      levels of tubulin (see Fig. 1 of this Amendment). In addition, the western blots
      for LSD1 and HDAC1 of Fig. 3b and c have been corrected to include vertical black
      lines to delineate the juxtaposition of lanes that were non-adjacent in the
      original blotting experiment (see Fig. 2 of this Amendment). Supplementary Figs.
      4a, 6b and 9b have also been corrected to delineate non-adjacent lanes with
      vertical black lines (see Supplementary Information of this Amendment). The
      complete raw data images from these western blotting experiments can also be
      found in the Supplementary Information of this Amendment. The original Letter has
      not been corrected.

PMID- 30209400
TI  - Cryo-EM structure of the active, Gs-protein complexed, human CGRP receptor.
AB  - Calcitonin gene-related peptide (CGRP) is a widely expressed neuropeptide that
      has a major role in sensory neurotransmission. The CGRP receptor is a heterodimer
      of the calcitonin receptor-like receptor (CLR) class B G-protein-coupled receptor
      and a type 1 transmembrane domain protein, receptor activity-modifying protein 1
      (RAMP1). Here we report the structure of the human CGRP receptor in complex with
      CGRP and the Gs-protein heterotrimer at 3.3 A global resolution, determined by
      Volta phase-plate cryo-electron microscopy. The receptor activity-modifying
      protein transmembrane domain sits at the interface between transmembrane domains
      3, 4 and 5 of CLR, and stabilizes CLR extracellular loop 2. RAMP1 makes only
      limited direct contact with CGRP, consistent with its function in allosteric
      modulation of CLR. Molecular dynamics simulations indicate that RAMP1 provides
      stability to the receptor complex, particularly in the positioning of the
      extracellular domain of CLR. This work provides insights into the control of G
      protein-coupled receptor function.

PMID- 30209402
TI  - CLL cells cumulate genetic aberrations prior to the first therapy even in
      outwardly inactive disease phase.

PMID- 30209403
TI  - Molecular pathogenesis of disease progression in MLL-rearranged AML.
AB  - Leukemic relapse is frequently accompanied by progressively aggressive clinical
      course. To understand the molecular mechanism of leukemic relapse, MLL/AF9
      transformed mouse leukemia cells were serially transplanted in C57BL/6 mice (N =
      96) by mimicking repeated recurrences, where mutations were monitored by exome
      sequencing (N = 42). The onset of leukemia was progressively promoted with
      advanced transplants, during which increasing numbers of somatic mutations were
      acquired (P < 0.005). Among these, mutations in Ptpn11 (p.G60R) and Braf
      (p.V637E) corresponded to those identified in human MLL-AML, while recurrent
      mutations affecting Msn (p.R295C) were observed only in mouse but not in human
      MLL-AML. Another mutated gene of interest was Gnb2 which was reported to be
      recurrently mutated in various hematological neoplasms. Gnb2 mutations (p.G77R)
      were significantly increased in clone size (P = 0.007) and associated with
      earlier leukemia onset (P = 0.011). GNB2 transcripts were significantly
      upregulated in human MLL-AML compared to MLL-negative AML (P < 0.05), which was
      supported by significantly increased Gnb2 transcript induced by MLL/AF9
      overexpression (P < 0.001). In in vivo model, both mutation and overexpression of
      GNB2 caused leukemogenesis, and downregulation of GNB2 expression reduced
      proliferative potential and survival benefit, suggesting a driver role of GNB2.
      In conclusion, alterations of driver genes over time may play an important role
      in the progression of MLL-AML.

PMID- 30209404
TI  - MARCKS regulates tonic and chronic active B cell receptor signaling.
AB  - Tonic or chronic active B-cell receptor (BCR) signaling is essential for the
      survival of normal or some malignant B cells, respectively. However, the
      molecular mechanism regulating the strength of these two types of BCR signaling
      remains unknown. Here, using high-speed high-resolution single-molecule tracking
      in live cells, we identified that PKCbeta, STIM1, and IP3R1/2/3 molecules
      affected the lateral Brownian mobile behavior of BCRs on the plasma membrane of
      quiescent B cells, which was correlated to the strength of BCR signaling. Further
      mechanistic studies revealed that these three molecules influenced BCR mobility
      by regulating the membrane tethering of MARCKS to the inner leaflet of the plasma
      membrane. Indeed, membrane-untethered or deficiency of MARCKS significantly
      decreased, while membrane-tethered or overexpression of MARCKS drastically
      increased the lateral mobility of BCRs. Functional experiments indicated that the
      membrane-tethered MARCKS suppressed the survival and/or proliferation in both B
      cell tumor cells and mouse primary splenic B cells in vitro and in vivo.
      Mechanistically, we found that membrane-tethered MARCKS increased BCR lateral
      mobility, and thus decreased BCR nanoclustering by disturbing the interaction
      between cortical F-actin and the inner leaflet of the plasma membrane, resulting
      in the suppression of the strength of both tonic and chronic active BCR
      signaling. Conclusively, MARCKS is a newly identified molecule regulating the
      strength of BCR signaling by modulating cytoskeleton and plasma membrane
      interactions, both in the physiological and pathological conditions, suggesting
      that MARCKS is a putative target for drug design.

PMID- 30209405
TI  - Doxorubicin induces an extensive transcriptional and metabolic rewiring in yeast
      cells.
AB  - Doxorubicin is one of the most effective chemotherapy drugs used against solid
      tumors in the treatment of several cancer types. Two different mechanisms, (i)
      intercalation of doxorubicin into DNA and inhibition of topoisomerase II leading
      to changes in chromatin structure, (ii) generation of free radicals and oxidative
      damage to biomolecules, have been proposed to explain the mode of action of this
      drug in cancer cells. A genome-wide integrative systems biology approach used in
      the present study to investigate the long-term effect of doxorubicin in
      Saccharomyces cerevisiae cells indicated the up-regulation of genes involved in
      response to oxidative stress as well as in Rad53 checkpoint sensing and signaling
      pathway. Modular analysis of the active sub-network has also revealed the
      induction of the genes significantly associated with nucleosome
      assembly/disassembly and DNA repair in response to doxorubicin. Furthermore, an
      extensive re-wiring of the metabolism was observed. In addition to glycolysis,
      and sulfate assimilation, several pathways related to ribosome
      biogenesis/translation, amino acid biosynthesis, nucleotide biosynthesis, de novo
      IMP biosynthesis and one-carbon metabolism were significantly repressed. Pentose
      phosphate pathway, MAPK signaling pathway biological processes associated with
      meiosis and sporulation were found to be induced in response to long-term
      exposure to doxorubicin in yeast cells.

PMID- 30209406
TI  - Redox control and autoxidation of class 1, 2 and 3 phytoglobins from Arabidopsis
      thaliana.
AB  - Despite a recent increase in interest towards phytoglobins and their importance
      in plants, much is still unknown regarding their biochemical/biophysical
      properties and physiological roles. The present study presents data on three
      recombinant Arabidopsis phytoglobins in terms of their UV-vis and Raman
      spectroscopic characteristics, redox state control, redox potentials and
      autoxidation rates. The latter are strongly influenced by pH for all three
      hemoglobins - (with a fundamental involvement of the distal histidine), as well
      as by added anion concentrations - suggesting either a process dominated by
      nucleophilic displacement of superoxide for AtHb2 or an inhibitory effect for
      AtHb1 and AtHb3. Reducing agents, such as ascorbate and glutathione, are found to
      either enhance- (presumably via direct electron transfer or via allosteric
      regulation) or prevent autoxidation. HbFe3+ reduction was possible in the
      presence of high (presumably not physiologically relevant) concentrations of
      NADH, glutathione and ascorbate, with differing behaviors for the three globins.
      The iron coordination sphere is found to affect the autoxidation, redox state
      interconversion and redox potentials in these three phytoglobins.

PMID- 30209408
TI  - TAK-137, an AMPA-R potentiator with little agonistic effect, has a wide
      therapeutic window.
AB  - Activation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor
      (AMPA-R) is a promising strategy to treat psychiatric and neurological diseases
      if issues of bell-shaped response and narrow safety margin against seizure can be
      overcome. Here, we show that structural interference at Ser743 in AMPA-R is a key
      to lower the agonistic effect of AMPA-R potentiators containing
      dihydropyridothiadiazine 2,2-dioxides skeleton. With this structural insight, TAK
      137, 9-(4-phenoxyphenyl)-3,4-dihydropyrido[2,1-c][1,2,4]thiadiazine 2,2-dioxide,
      was discovered as a novel AMPA-R potentiator with a lower agonistic effect than
      an AMPA-R potentiator LY451646 ((R)-N-(2-(4'-cyanobiphenyl-4-yl)propyl)propane-2
      sulfonamide) in rat primary neurons. TAK-137 induced brain-derived neurotrophic
      factor in neurons in rodents and potently improved cognition in both rats and
      monkeys. Compared to LY451646, TAK-137 had a wider safety margin against seizure
      in rats. TAK-137 enhanced neural progenitor proliferation over a broader range of
      doses in rodents. Thus, TAK-137 is a promising AMPA-R potentiator with potent
      procognitive effects and lower risks of bell-shaped response and seizure. These
      data may open the door for the development of AMPA-R potentiators as therapeutic
      drugs for psychiatric and neurological diseases.

PMID- 30209407
TI  - Increased risk of diseases of the basal ganglia and cerebellum in patients with a
      history of attention-deficit/hyperactivity disorder.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is marked by an ongoing pattern
      of inattention and/or hyperactivity and involves dysregulated dopaminergic
      pathways. Dopaminergic agents (i.e., amphetamine and methylphenidate) are thus
      prescribed to treat ADHD. As little is known regarding long-term consequences of
      either ADHD or its treatment, the objective of this study was to determine if
      either alters the risk of diseases of the basal ganglia and cerebellum, including
      Parkinson's disease. Statewide medical records from 1996 to 2016 were retrieved
      from the Utah Population Database to conduct a retrospective cohort study.
      Participants included ADHD patients (International Classification of Diseases,
      9th revision (ICD-9) diagnosis codes 314.0-314.2, 314.8, 314.9) and 5:1 random
      sex-matched and age-matched subjects with no ADHD diagnosis history. Both
      patients and non-ADHD subjects met the following eligibility criteria: (1) no
      prior diagnosis of Parkinson's disease, secondary parkinsonism, basal ganglia
      disease, or essential tremor (ICD-9 codes 332.0, 332.1, 333.0, 333.1), (2) born
      in 1950 or later and age >=20 years at last follow-up, and (3) no history of
      substance abuse (illicit drugs or alcohol). Outcomes were measured as time to
      diagnosis of diseases of the basal ganglia and cerebellum, death, or study-end. A
      Cox model incorporating a competing risk of death was used to provide hazard
      ratio estimates. Patients with ADHD (N = 31,769) had a 2.4-fold increased risk of
      basal ganglia and cerebellum diseases (95% confidence interval (CI): 2.0-3.0; P <
      0.0001) compared with 158,790 non-ADHD persons, after controlling for sex and age
      and adjusting for tobacco use and psychotic conditions. In 4960 ADHD patients
      prescribed psychostimulants, risk of basal ganglia and cerebellum diseases
      between ages 21 and 49 years was especially pronounced, at 8.6-fold (95% CI: 4.8
      15.6; P < 0001). The association of ADHD patients prescribed psychostimulants
      with higher risk of diseases of the basal ganglia and cerebellum may reflect a
      more severe ADHD phenotype rather than a direct association between prescribed
      stimulant use and basal ganglia or cerebellum disorders. Future studies to assess
      and stratify patient risk so as to inform treatment are warranted.

PMID- 30209411
TI  - New advice to give patients a helping hand.

PMID- 30209412
TI  - Distinguishing NET subtypes.

PMID- 30209410
TI  - The induced by an electromagnetic field coexistence of types I and II spectra in
      Weyl semimetals.
AB  - Due to their unique properties, Weyl semimetals (WSMs) are promising materials
      for the future electronics. Currently, the two types (I and II) of WSMs are
      discovered experimentally. These types of WSMs differ from each other in their
      topological properties. In this paper we showed that a coexistence of types I and
      II Weyls spectra is possible in some WSMs under crossed magnetic and electric
      fields. This is possible in systems with non-equivalent Weyl points (WPs). In
      particular, it is possible in strained WSMs. Such phase, controlled by
      electromagnetic field, is principally new for topological matter physics. It is
      obvious, that in this regime new features of electron transport will appear. We
      showed that this effect can also be considered as a mechanism of strain induced
      type-I-type-II transition.

PMID- 30209409
TI  - The serine/threonine kinase Stk and the phosphatase Stp regulate cell wall
      synthesis in Staphylococcus aureus.
AB  - The cell wall synthesis pathway producing peptidoglycan is a highly coordinated
      and tightly regulated process. Although the major components of bacterial cell
      walls have been known for decades, the complex regulatory network controlling
      peptidoglycan synthesis and many details of the cell division machinery are not
      well understood. The eukaryotic-like serine/threonine kinase Stk and the cognate
      phosphatase Stp play an important role in cell wall biosynthesis and drug
      resistance in S. aureus. We show that stp deletion has a pronounced impact on
      cell wall synthesis. Deletion of stp leads to a thicker cell wall and decreases
      susceptibility to lysostaphin. Stationary phase Deltastp cells accumulate
      peptidoglycan precursors and incorporate higher amounts of incomplete
      muropeptides with non-glycine, monoglycine and monoalanine interpeptide bridges
      into the cell wall. In line with this cell wall phenotype, we demonstrate that
      the lipid II:glycine glycyltransferase FemX can be phosphorylated by the Ser/Thr
      kinase Stk in vitro. Mass spectrometric analyses identify Thr32, Thr36 and Ser415
      as phosphoacceptors. The cognate phosphatase Stp dephosphorylates these
      phosphorylation sites. Moreover, Stk interacts with FemA and FemB, but is unable
      to phosphorylate them. Our data indicate that Stk and Stp modulate cell wall
      synthesis and cell division at several levels.

PMID- 30209413
TI  - Modern-day environmental factors in the pathogenesis of osteoarthritis.
AB  - The prevalence of osteoarthritis (OA) is rising for reasons that are not fully
      understood. In this Opinion article, we review the possibility that OA is an
      evolutionary mismatch disease, which is a disease more common today than in the
      past because genes inherited from previous generations are inadequately or
      imperfectly adapted to modern environmental conditions. We focus on four major
      environmental factors in OA pathogenesis that have become ubiquitous within the
      past half-century: obesity, metabolic syndrome, dietary changes and physical
      inactivity. Because a cure for OA does not yet exist, prevention strategies that
      target these modifiable environmental factors are needed to curb further
      increases in OA prevalence.

PMID- 30209415
TI  - The contribution of dogs and other animals to social inclusion programmes.
AB  - Animal-assisted interventions refer to any intervention that intentionally
      includes or incorporates animals as part of a therapeutic, palliative,
      educational, psychoeducational or recreational process or milieu. The Faculty of
      Veterinary Science of the University of Buenos Aires began work on this issue in
      1996 and gradually incorporated outreach, research and teaching projects,
      undertaking several stages of institutionalisation and reconceptionalisation that
      led, in 2014, to the creation of an open chair in animal-assisted interventions.
      This article aims to introduce the discipline, with special emphasis on its
      potential as a means of promoting inclusion, and to present a specific case of
      work with dogs, which began in 2009 with the non-profit organisation Senderos del
      Sembrador (Trails of the Sower) for people with an intellectual disability who
      are in great need of support. This article describes how the contact with dogs
      was systematised, along with outcomes, challenges and difficulties, and how
      leisure came to be used as a means of promoting inclusion and altering the
      preconceptions of people without disabilities. Finally, in reflecting on
      practices, the project evolved from a treatment plan for rehabilitating people
      with disabilities into a space for effective social inclusion that gradually
      changed the perceptions and practices of all participants.

PMID- 30209414
TI  - Mixed-species grazing management to improve sustainability and biodiversity.
AB  - Mixed-grazing systems occur when two or more large herbivores graze together.
      Body size and anatomical differences between animal species are reflected in
      differences in their selected diet and foraging behaviour, which can bring about
      opportunities for complementary pasture use. The extent to which niche separation
      occurs within farming systems depends on the degree of sward heterogeneity and
      the scale of the resource available, with cultivated swards generally offering
      comparatively little occasion for selective grazing, in comparison to native
      pastures. However, even then there are opportunities for mixed grazing to benefit
      productivity. A range of studies have shown that if sheep are grazed together
      with cattle on simple grass/white clover swards, the performance of the sheep is
      improved in comparison to sheep-only grazing, leading to a higher total output
      per unit area. Semi-natural vegetation communities offer much more opportunity
      for selective grazing as they are generally more botanically and structurally
      diverse. Examples are given of the impact of losing large and small grazers from
      grazed ecosystems in marginal areas. Loss of cattle grazing from the uplands of
      Wales has been instrumental in the spread of invasive hill grass species linked
      to the loss of heathland habitats of international conservation importance.
      Conversely, the loss of sheep and goats from common lands in the Cantabrian
      Mountains has led to the progressive expansion of woody vegetation, again at the
      expense of heathlands. Such examples highlight the role that mixed grazing can
      play in promoting economic and environmental sustainability, particularly in
      marginal areas.

PMID- 30209416
TI  - Facing disasters together: how keeping animals safe benefits humans before,
      during and after natural disasters.
AB  - More than half of the world's households are thought to contain at least one
      companion animal. Animals can affect how humans are impacted by natural
      disasters, how they respond to such events and how well they can recover from
      them. For this reason alone, there is a real need to keep animals safe before,
      during and after natural disasters, and to do so in ways that contribute to,
      rather than compromise, human safety. This paper outlines the negative
      implications of failing to account for animals in disaster plans and/or to
      accommodate them in shelters. It also outlines how including animals in disaster
      response can provide benefits for the physical and mental health and well-being
      of humans that extend well beyond the disaster event. These implications are
      discussed in broad terms for the guardians of small and large companion animals,
      livestock producers and emergency responders with examples drawn from a variety
      of natural and human-made hazards. Finally, this paper suggests that research on
      people who do not attempt to save, rescue or evacuate with animals could provide
      important insights into natural disaster behaviour and human-animal relations.

PMID- 30209417
TI  - The contribution of rescue dogs during natural disasters.
AB  - As a species, dogs are particularly suited to working with as well as working for
      humankind on a variety of tasks, including searching for victims of natural
      disasters. Their abilities are deeply seated within their genetic make-up and
      their domestication over thousands of years. Dogs display not only a natural
      ability to find people, but also to aid and protect them. Military organisations
      throughout the ages have recognised these traits and shaped canine behaviour to
      help them in their endeavours on and off the battlefield. Scientific discovery,
      genetics and breeding, as well as advances in positive training methods, combine
      to create a unique and unsurpassed search team - canine and handler. Nature and
      nurture have created more than a living mechanism for rescue workers, however.
      The emotional benefits and support provided by dogs for responders and victims
      alike are a profound adjunct to their work as search dogs.

PMID- 30209418
TI  - Operational impact of canine teams in the fight against drug trafficking in
      Colombia: review of their contribution, strategies and recent trends.
AB  - As part of national and international cooperation to fight the drug-trafficking
      system, the Colombian National Police (PNC) has created institutional operational
      synergy to combat organised armed groups. To this end, it uses police service dog
      and handler teams which are distributed across Colombia in 75 canine units and
      which are specialised in different policing tasks. The focus of canine teams is
      to counter actions that undermine peaceful co-existence and citizen security by
      checking for explosive substances around coca, marijuana and poppy fields. In
      2016, these teams discovered 16% of the 12,500 kg of improvised explosive
      devices, anti-personnel mines and unexploded ordnance (conventional guns and
      grenades) that were seized by the PNC. In addition, dogs have detected 19% of all
      controlled substances (cocaine, marijuana, heroin, coca paste and synthetic
      drugs) seized at ports, airports, land terminals and highways, striking a blow at
      drug-trafficking structures at all stages, from the illicit cultivation of drugs,
      through to their production, distribution, sale and use, countering small-scale
      dealing and the factors associated with drug-related social disorder. It is the
      responsibility of the PNC Police Service Dog and Handler Training School (ESGAC)
      to provide a framework for academic endeavour and technological advances aimed at
      achieving defined strategic roles for dog and handler teams. This involves the
      genetic selection and breeding of candidate detection dogs, assessment, training,
      operant conditioning, odour-discrimination during searches, certification, dog/
      handler relationship, the dogs' living environment, and animal health, production
      and welfare management. All of the above is designed to achieve real, effective
      and successful outcomes when policing with dogs, enshrined within the national
      government's Vision 2030 project for safe and peaceful communities.

PMID- 30209420
TI  - A veterinary perspective on preventing injuries and other problems that shorten
      the life of working dogs.
AB  - Domesticated dogs are widely used for farm work, law enforcement, military
      service and in assistance roles. Farm dogs assist farmers by guarding or moving
      stock, reducing the requirement for human workers and enabling steep terrain to
      be productive. Working and service dogs are subject to illness and injury,
      depending on their breed characteristics, activities and the environment in which
      they work. There are limited data in the veterinary literature on the causes of
      loss and early retirement of working dogs, and targeted research is required to
      better determine factors that affect their incidence. Many breeds of working dog
      suffer from inherited forms of musculoskeletal disease; most importantly, elbow
      and hip dysplasia. The effectiveness of traditional radiographic (phenotypic)
      scoring schemes at reducing the prevalence of hip and elbow dysplasia has been
      variable. The selection of breeding stock should preferably be based on estimated
      breeding values, rather than on an individual phenotypic score/grade. Nutrition
      can affect physical and mental performance, disease risk and susceptibility, and
      recovery from injury, age-associated decline and longevity. The dietary
      proportions of fat, protein and carbohydrate influence fuel selection during
      exercise. A common concern among farmers is the difficulty of maintaining body
      condition in their dogs during periods of heavy work with current feeding
      practices. Additionally, maintaining a positive calcium balance is necessary for
      adaptive remodelling in response to exercise. Research strategies should include
      improved treatment options, the development of more specific means of genetic
      selection for inherited diseases, investigation into specific nutritional
      requirements and the dissemination of this knowledge.

PMID- 30209419
TI  - Prisoner rehabilitation through animal-assisted activities in Argentina: the
      Huellas de Esperanza Prison Dog Programme.
AB  - One of the most traumatic events that a person can ever experience in their
      lifetime is being detained. The prison dog programmes are the most successful
      prison rehabilitation programmes in the United States of America and consist of
      detainees training service dogs for other people to assist with different types
      of disability. It is a typical win-win system: inmates win as they connect with
      their deepest feelings of affection and solidarity while acquiring a concrete
      skill for their future release; people with disabilities win because they receive
      a dog to support their day-to-day activities; the dogs win (especially adopted
      street dogs) because their lot in life is improved; institutions win because they
      are enabled to meet their objective more fully; and society wins because they
      gain a concrete tool to aid the social rehabilitation of detainees. This article
      describes the operation and achievements of Huellas de Esperanza (Traces of
      Hope), the Argentine prison dog programme, which has been implemented by the
      Federal Penitentiary Service since 2010 using State resources. A total of 85
      inmates have participated in the programme, which has delivered more than a dozen
      assistance dogs to people with disabilities and many more dogs to elderly people
      to provide them with affection and companionship. The article also describes the
      programme methodology and the way it has decreased prison unrest and led to a low
      reoffending rate among programme participants.

PMID- 30209421
TI  - Preventing skeletal and neurological problems in guide dogs for the blind and
      other working dogs.
AB  - Skeletal and neurological problems consistently rank among the top health
      conditions necessitating the withdrawal or retirement of guide dogs and other
      working dogs from their service roles. Management practices such as weight
      management and physical conditioning may help to reduce the incidence of such
      conditions. However, where there is at least partial genetic aetiology, selective
      breeding strategies are the only way to produce a lasting reduction in their
      incidence in future generations. The management of single gene disorders is
      relatively simple through the judicious use of DNA test results. Breeding
      strategies to tackle complex diseases, into which category many skeletal and
      neurological diseases fall, are more challenging but can be successful through
      the use of data collected through screening schemes and, most efficiently,
      through the use of estimated breeding values.

PMID- 30209422
TI  - The role of therapy and service animals in the lives of persons with
      disabilities.
AB  - Over the past 20 years, a great deal of attention has been paid to the
      psychological and physiological impact that animals have on the lives of people
      with disabilities. The focus of this paper is to demystify the mechanisms that
      are affected as a consequence of these interactions as well as to describe the
      value of various types of therapeutic working animals. For human-animal
      interactions to become more legitimised, more rigorous empirical research needs
      to be undertaken to demonstrate the value of such interactions as well as the
      need for changes in the public policy impacting them.

PMID- 30209423
TI  - Production of pharmaceutical proteins by transgenic animals.
AB  - Proteins are involved in a majority of the biochemical events that take place in
      all living organisms. Protein synthesis is directed by genes. All genes contain
      two major DNA regions. The region containing the genetic message proper (the
      'coding region') is preceded by a regulatory region ('the promoter'), which
      determines when and in which organs a given gene must produce the corresponding
      protein. The techniques of genetic engineering allow the association of the
      coding region from one gene with the regulatory region from another gene. The
      expression of these recombinant genes may be achieved in cultured cells, in
      transgenic animals or in plants. This leads to the production of the
      corresponding proteins, including pharmaceutical proteins. Milk from transgenic
      animals is one potential source of pharmaceutical proteins. To achieve this, the
      promoters from milk protein genes are bound to DNA fragments containing the
      coding region of the genes of interest. The desired proteins are then taken from
      the milk and purified. Two human pharmaceutical proteins are on the market and
      about 20 projects are in development. One of the proteins produced in milk,
      antithrombin III, is an anticoagulant and the other, human C1-esterase inhibitor,
      is an anti-inflammatory. Several human proteins have been produced in the egg
      white of transgenic chickens and one has been approved by the United States
      Federal Drug Administration. This process has also been used to modify antibodies
      in cows. The genes that code for antibodies in the cow were deleted and replaced
      by human antibody genes. These cows, immunised by various antigens, then secreted
      purely human antibodies in their blood. Antibodies from such cows were able to
      attenuate the effects of Ebola virus in human patients.

PMID- 30209424
TI  - Ethical issues surrounding the transplantation of organs from animals into
      humans.
AB  - In this paper, the authors provide an analysis of the ethical issues surrounding
      the transplantation of organs from animals into humans. The main objections to
      xenotransplantation relate to safety concerns for the recipient; public health
      concerns about new viruses spreading from animals to humans; the possibility of
      animals developing human features; concerns about human dignity; and the fact
      that animals must be sacrificed so humans can benefit from their organs. Despite
      these objections, the urgency of the organ shortage situation is such that
      xenotransplantation may be justified, if further advances make it a realistic
      possibility.

PMID- 30209425
TI  - Cellular xenotransplantation of animal cells into people: benefits and risk.
AB  - The main benefit of xenotransplantation is its potential to overcome the
      worldwide organ shortage experienced in allotransplantation. Allogeneic
      transplantation is the only successful therapy for several life-threatening
      diseases, with cell, tissue or organ donation only partially meeting the demand
      and many patients dying while waiting for treatment. With supply falling short of
      demand, it is foreseen that the use of porcine material may at some stage
      overcome the existing gap between organ availability and clinical need. Recently,
      pig islet cells have been utilised in clinical trials, with safety being
      demonstrated. Indeed, pig-derived cells present several advantages: i) porcine
      cells have a stable function and differentiation pattern and are not tumorigenic;
      ii) pig cells have been shown to meet the physiological needs in large animal
      models; iii) the source of pig cells can be scaled up to meet demands in a highly
      standardised manner, and with respect to animal welfare regulations; iv)
      'designated-pathogen-free' (DPF) pig lines can be produced, which could result in
      a higher safety profile than allotransplantation itself; v) the risk of zoonosis,
      which was raised years ago as the major hurdle, has been recently circumvented
      and is actually viewed as a controlled risk; and vi) immune risks are being
      circumvented via the use of genetically modified donor animals and encapsulation
      of porcine cells, particularly for the treatment of diabetes. Overall, the
      benefit appears to outweigh potential risks with respect to cellular
      xenotransplantation and this is discussed further in this review.

PMID- 30209426
TI  - The contribution of transgenic and genome-edited animals to agricultural and
      industrial applications.
AB  - For centuries, animal breeders have intentionally selected the parents of the
      next generation based on their concept of the 'ideal' animal. The dramatic
      differences seen in the appearance and productivity of different breeds show the
      power of such selection on DNA sequence variations. Unfortunately, the global
      furore over the use of modern biotechnologies to introduce desired genetic
      variations into animal breeding programmes, and the regulatory uncertainty
      associated with these recombinant DNA techniques, has effectively precluded the
      use of these technologies in food animal breeding programmes. Ironically, many of
      these early transgenic animal applications targeted traits that favoured
      sustainability, such as disease resistance and decreased environmental impact. As
      a consequence, transgenic animals have had little opportunity to affect global
      agriculture, and only a handful of pharmaceutical applications have been
      successfully commercialised. New developments in genome editing hold considerable
      promise for targeting traits that improve both animal health and welfare, and
      frequently involve no introduction of DNA sequences from other species.
      Nonetheless, future global regulation and public acceptance of such methods
      remain uncertain. Proposals to regulate genome-edited animals based solely on the
      process used to influence DNA sequence variations (i.e. intentional genome
      editing) and any potential attendant risks, with no counterbalancing
      consideration of the ensuing benefits or risks associated with conventional
      selection programmes, will potentially forestall the use of genome editing in
      animal breeding programmes. No activity can survive a risk-only evaluation, and
      there are considerable opportunity costs associated with preventing breeders'
      access to safe technologies in order to achieve genetic improvements in livestock
      populations.

PMID- 30209427
TI  - How farm animals are improving human health and welfare.
AB  - The contribution of farm animals to human health and welfare cannot be properly
      addressed without reflecting on the impact that animal domestication has had upon
      human civilisation. About 14,000 years ago, the Neolithic revolution started with
      the domestication of animals and plants, resulting in the emergence of the main
      agricultural breeds of livestock and crops. In contrast, the breeding of new
      animal species for biomedical research, such as small rodents and other model
      species, is a relatively recent activity. The cellular and molecular mechanisms
      of inheritance have only been understood over the past few decades and translated
      into approaches to improve breeding success. In recent years, seminal discoveries
      in the fields of cellular reprogramming, genetic engineering, and whole-genome
      sequencing have accelerated this development. The first therapeutic proteins
      produced by biopharming in livestock have been approved to treat human patients.
      The suitability of pluripotent stem cells as a source for cell replacement
      therapies is currently being investigated, using farm animals as informative
      preclinical models. Disease modelling in farm animals allows systematic testing
      of effective treatments. Within the context of these developments, this concise
      review will focus on the contribution of farm animals to human health and
      welfare.

PMID- 30209428
TI  - Companion animals and human health: benefits, challenges, and the road ahead for
      human-animal interaction.
AB  - There is ample evidence that human-animal interaction (HAI) is associated with
      health. Studies encompass three general categories: those that compare companion
      animal owners with individuals who do not own companion animals, those examining
      brief, 'one-off' contacts with animals, and those that review animal-assisted
      interventions. The health benefits demonstrated typically include reductions in
      depression and loneliness, while enhancing social interaction or social skills,
      and decreasing anxiety and arousal. Other health benefits associated with
      companion animals include the promotion of exercise or physical activity. The
      types of human-animal contact that have been evaluated include visual contact,
      physical contact, and looking at images of animals. The species used in
      interventions include dogs, cats, horses, rabbits, goats, hamsters and crickets.
      Despite these benefits, HAIs are also associated with problems, including
      allergies, asthma, zoonoses, animal bites and scratches, and human falls. Other
      problems include grief and negative emotions when a companion animal is injured
      or dies. Companion animal ownership is also expensive. Inconsistent policies
      concerning keeping animals in housing and enabling service animals to access
      public places make it difficult to live with companion animals or keep service
      animals in some circumstances. Additional research is needed to provide an
      evidence base to evaluate the efficacy of particular types of HAI using a given
      type of animal. This will document specific outcomes for an individual with
      certain characteristics and assist in promoting the future use of HAI to enhance
      human and animal health and well-being.

PMID- 30209429
TI  - Increasing omega-3 levels in meat from ruminants under pasture-based systems.
AB  - This review discusses the importance of red meat from ruminants as a source of
      omega-3 (n-3) fatty acids (FAs) for human life in the context of the contribution
      of animals to human welfare. Red meat is a valuable food commodity for human life
      because it is naturally rich in key nutrients such as protein, trace elements,
      vitamins and essential FAs. In developed countries and high socio-economic groups
      from developing countries, red meat intake is greater than that of oily fish,
      owing to availability, preference and affordability. Omega-3 FA concentration is
      higher in red meat (beef, lamb and mutton) than in white meat (pork, poultry and
      turkey), due to the fibre types present in muscle tissues and the specialised
      digestive systems of ruminants. There is mounting evidence that regular
      consumption of n-3 FAs is beneficial for growth and development as well as the
      health and welfare of humans of all ages. The dietary background of ruminants
      significantly influences the concentration of n-3 FAs in red meat. Meat from
      forage- or grassfed ruminants has a greater concentration of n-3 FAs than that
      from their feedlot or grain-fed counterparts and can also offer a favourable n
      6:n-3 ratio in the meat. Scientific literature shows that the advantages of
      consuming n-3 FAs enriched meat (foods) outweigh the disadvantages.

PMID- 30209430
TI  - The effects of meat consumption on global health.
AB  - Meat represents an important source of high-quality dietary protein for a large
      proportion of the global population. In addition, red meat, in particular,
      significantly contributes to the intake of a wide range of micronutrients,
      including iron, zinc, selenium, vitamin D and vitamin B12. While these nutrients
      can be supplied in sufficient amounts by consumption of a range of fruit and
      vegetables, in many developing countries, where the availability of such foods
      may be limited, access to meat often protects against malnutrition and improves
      child cognitive development. Excessive consumption of meat and meat products is
      often associated with overconsumption of energy and fat, resulting in excess
      weight, obesity and an increased risk of chronic diseases, such as cardiovascular
      disease and type 2 diabetes. In addition, certain components of fresh and
      processed red meat may further increase the risk of these diseases and predispose
      the consumer to cancer, particularly colorectal cancer. In the face of population
      growth and global warming, there is increasing concern about the sustainability
      of farm animal production. Thus, while a modest intake of meat represents an
      important strategy to avoid essential nutrient deficiencies, limiting its intake
      can reduce the development of a range of chronic diseases and could have
      significant beneficial effects on global food security.

PMID- 30209431
TI  - The benefits of animal products for child nutrition in developing countries.
AB  - One in five children across the globe experience stunted growth and
      underdevelopment due to malnutrition. Animal-source foods (ASFs) offer the
      opportunity to address this problem and make significant progress towards
      achieving the World Health Assembly nutrition targets. Eggs and milk are among
      nature's first foods, providing holistic packages of nutrients and bioactive
      factors to support healthy growth. They are also affordable and accessible to
      lowresource, vulnerable populations. Biological and evolutionary rationale argues
      for the use of ASFs during the complementary feeding period when children are
      most at risk from infectious diseases and malnutrition. Dietary patterns in the
      evolutionary history of hominids point to the importance of ASFs for increased
      brain size and function. Studies also demonstrate high bioavailability of
      limiting nutrients, such as vitamin A, iron, zinc and fatty acids in the ASF
      matrix, ensuring efficient absorption and metabolism. The empirical evidence for
      intervention using eggs, milk and fish, however, remains somewhat limited. One
      recent trial in Ecuador, the Lulun Project, demonstrated that one egg per day for
      six months, beginning early in complementary feeding, produced a large effect on
      linear growth and reduced stunting risk by 47%. To sustainably build systems that
      support equitable and adequate ASFs in the diets of all children globally,
      consideration should be given to microeconomic and macroeconomic factors, 'One
      Health', and maintaining balance in the ecosystem. Important contributions may
      then be achieved through ASFs for the well-being of populations worldwide.

PMID- 30209432
TI  - Introduction: The contribution of animals to human welfare.
AB  - Animals contribute to the lives of humans in developed and developing countries
      in numerous ways. Here, the focus is on how grazing animals can contribute to
      human lives and on the many ways in which dogs are of benefit to humans. Grazing
      is a sustainable practice which allows uncultivable land to be used for the
      production of food, prevents the degradation of land, and does not lead to the
      depletion of groundwater, thus contributing to food security. Dogs provide help
      during rescues, companionship, and support for livelihoods. It is vital to ensure
      the welfare of the farm animals that provide us with so much, and the author
      discusses outcome-based welfare indicators, such as lameness, sickness and
      lesions, that can be used in both developed and developing countries to prevent
      suffering. In recent times, animal welfare science has begun to look at the
      emotional state of animals, but it is important to recognise that in developing
      countries, where finding enough food is the biggest concern, the animal's
      positive emotions cannot be a top priority. The paper ends by emphasising the
      importance of local solutions for improving the health and welfare of both
      animals and humans. There is a need for successful local programmes to be rolled
      out on a wider basis. To encourage the spread of effective programmes, people
      need to write about them.

PMID- 30209433
TI  - Preface: The contribution of animals to human welfare.

PMID- 30209434
TI  - Conservation of rare and local breeds of livestock.
AB  - The genetic diversity of domesticated species is contained within breeds, with
      the result that conserving breeds conserves this diversity. Breeds are
      predictable genetic resources that allow a match of animals with different
      environments and production goals. Breeds were developed through a process
      involving foundation, isolation and selection. Breed types that qualify as
      genetic resources include 'landraces' (local breeds), standardised breeds,
      commercial production breeds and feral livestock that have returned to a free
      living state. Currently, breeds of all classes are threatened with extinction.
      The reasons for breed conservation include maintaining breed diversity for future
      needs, cultural connections between people and breeds, and material for
      scientific investigation. Several breeds have undergone genetic adaptations that
      make them uniquely suited to specific challenging environments. Conservation
      depends upon discovering these genetic resources, securing them with a good
      genetic structure, and subsequently sustaining them for long-term survival with
      demand for the breed and its products.

PMID- 30209435
TI  - Apparent foreign-body-like structure detected in the left atrium after catheter
      ablation for persistent atrial fibrillation.
AB  - BACKGROUND: A foreign body left in left atrium after catheter ablation of atrial
      fibrillation is a very rare complication. Nevertheless, there are no reports so
      far about a large newly emerged structure only giving the impression of being a
      foreign body left in the heart after catheter ablation. CASE REPORT: This report
      presents a case of a patient after catheter ablation for persistent atrial
      fibrillation. Because of atrial tachycardia during follow-up, patient was
      indicated for reablation. Imaging methods including intracardiac echocardiography
      showed a straw-like foreign body with the character of a transseptal sheath in
      left atrium. A cardiac surgery was performed with extraction of the foreign body.
      We found a fibrous chord-like material in the left atrium, microscopy showed
      myocardial tissue with continuous transition to fibrinous elastic vessel. No
      signs of foreign material were found. CONCLUSION: We have found a newly emerged
      body giving the impression of being of foreign origin in left atrium after
      catheter ablation of atrial fibrillation. Microscopy of the extracted material
      showed myocardial tissue with continuous transition to fibrinous elastic vessel
      and a fibrinous tissue with focal dystrophic calcification. Its origin remains
      unknown.

PMID- 30209436
TI  - Abdominal wall allotransplantation.
AB  - Allotransplantation of vascularized composite tissue is a new field of
      transplantation surgery. One application of this technique is abdominal wall
      transplantation used as a supplementary procedure to the transplantation of
      visceral organs in patients with abdominal compartment deficits. As abdominal
      wall closure problems are experienced in around 30-40% of such patients, peer
      reviewed conclusions on the viability of various options, are important for an
      informed choice of possible procedures. This review focuses on the abdominal wall
      allotransplantion procedure. Our search provided 35 appropriate references which
      we used to support our findings as follows: abdominal wall transplantation was
      performed in 33 patients at seven centres. Of these, 30 had a full thickness
      abdominal wall transplanted from the same donor, 3 from a second donor. Three had
      visceral organ transplants and in addition, the posterior sheet of the rectus
      muscle fascia. In summary, our findings were that abdominal wall
      allotransplantation does not jeopardize the outcome of visceral organs
      transplantation. There is no higher risk of complications or rejection of the
      visceral organs. There have been no fatalities as a direct result of
      complications due to abdominal wall transplantation. Finally, the transplanted
      abdominal wall may provide an early warning of rejection before diagnostic tests
      on the bowel are symptomatic.

PMID- 30209437
TI  - Intestinal dysbiosis and hormonal neuroendocrine secretion in the fibromyalgic
      patient: Relationship and correlations.
AB  - Fibromyalgia is a rheumatic syndrome and its pathogenesis is controversial. The
      recent literature has placed considerable attention on the link between
      alteration of the intestinal microbiota and fibromyalgia, emphasizing the close
      connection between the neuroenteric system and the CNS. This study aims to
      evaluate the probable relationship between intestinal dysbiosis and altered
      secretion of hormones and vitamins such as cortisol, serotonin, Vitamin D and
      thyroid hormones in a patient with fibromyalgia.

PMID- 30209438
TI  - Association of serum adipocyte fatty acid-binding protein and apolipoprotein B
      /apolipoprotein A1 ratio with intima media thickness of common carotid artery in
      dyslipidemic patients.
AB  - BACKGROUND: Diseases caused by atherosclerosis play the most important role in
      mortality and morbidity worldwide. Serum adipocyte fatty acid binding protein (A
      FABP) seems to be a new promising marker to determine the risk of
      atherosclerosis. OBJECTIVE: The aim of this study was to evaluate relationships
      between serum A-FABP levels in studied individuals and to assess the possibility
      of modeling the intima media thickness of the common carotid artery (C-IMT) using
      A-FABP levels and other observed characteristics. METHODS: Seventy two Caucasian
      individuals were enrolled and divided into 3 groups: dyslipidemic patients with
      or without metabolic syndrome (MetS+, n=17; MetS-, n= 34) and controls (n=21).
      RESULTS: There was confirmed the well-established risk profile of individuals
      with MetS (unfavorable lipid and lipoprotein profile, as well as increased
      parameters of insulin resistence and C-IMT). A-FABP concentrations in this group
      were significantly higher in comparison with both MetS- and controls. CONCLUSION:
      Using multiple linear regression models of C-IMT values for all individual data,
      healthy controls and dyslipidemic patients without metabolic syndrome (MetS-) A
      FABP levels were not revealed as an important predictor of C-IMT in our model. In
      contrast, age, gender, waist circumference, nonHDL cholesterol levels and
      ApoB/ApoA1 ratio were important repressors of C- IMT in study individuals. This
      finding may be attributed to the overwhelming effect of other more robust risk
      factors for atherosclerosis in these individuals.

PMID- 30209439
TI  - Normotensive glaucoma.
AB  - This article provides an updated overview of the structural and functional
      changes in normotensive glaucoma and its variations from hypertensive glaucoma.
      The authors point out the less familiar facts in which both diagnostic groups
      differ.

PMID- 30209440
TI  - An update of lanreotide acetate for treatment of adults with carcinoid syndrome.
AB  - Carcinoid tumors are rare and usually slow-growing. Some patients with advanced
      metastatic disease however can develop symptoms of carcinoid syndrome, which
      results in debilitating diarrhea and flushing. Many treatments including
      chemotherapy were tried unsuccessfully in the past to treat this syndrome. The
      symptoms of carcinoid syndrome are thought to be related to the ability of the
      tumors to produce serotonin. The discovery that the production of this hormone
      can be inhibited by somatostatin led to the development of somatostatin analogues
      octreotide and lanreotide, which differ from native somatostatin in that they
      have a longer half-life. These compounds have shown dramatic responses in symptom
      control and reduction of serotonin metabolites including urinary 5
      hydroxyindoleacetic acid (5-HIAA) levels. This review researches the origins of
      carcinoid tumors, the development of lanreotide as a treatment and future
      directions for the treatment of carcinoid syndrome.

PMID- 30209441
TI  - Netarsudil ophthalmic solution 0.02% for the treatment of patients with open
      angle glaucoma or ocular hypertension.
AB  - Once-daily (p.m.) netarsudil ophthalmic solution 0.02% (Rhopressa) is approved in
      the United States for lowering elevated intraocular pressure (IOP) in patients
      with open-angle glaucoma or ocular hypertension. Netarsudil, a Rho kinase (ROCK)
      inhibitor that lowers IOP primarily by increasing trabecular outflow, produces
      statistically and clinically significant reductions in mean IOP from baseline,
      with comparable effects on nocturnal and diurnal IOP. In three phase III trials
      of patients with elevated IOP, the ocular hypotensive efficacy of once-daily
      netarsudil 0.02% met the criteria for noninferiority to twice-daily timolol 0.5%
      at all time points over 3 months in patients with baseline IOP less than 25 mmHg.
      The most frequent adverse event (AE) was generally mild conjunctival hyperemia,
      the severity of which did not increase with continued dosing. Netarsudil was
      associated with minimal treatment-related serious or systemic AEs, likely due to
      the lack of systemic exposure. This report summarizes the available preclinical
      and clinical data on netarsudil.

PMID- 30209442
TI  - Targeted agents in the management of small cell lung cancer - present and future.
AB  - Lung cancer is the leading cause of cancer-related mortality worldwide and is the
      second most common cancer in both sexes. The small cell lung cancer (SCLC)
      subtype constitutes about 13% to 15% of all diagnosed lung cancers with an
      expected 5-year mortality of about 90%. In the past decades, various strategies
      used to treat newly diagnosed, relapsed or refractory SCLC have shown no
      significant improvement in clinical outcomes. In the genomic era of oncology,
      with a better understanding of tumor biology and pathway specific investigations,
      multiple investigational agents have been studied with the aim to improve
      clinical outcomes. Some of them include epidermal growth factor receptor tyrosine
      kinase inhibitors (EGFR-TKIs), BCR-ABL TKIs, mammalian target of rapamycin (mTOR)
      inhibitors, vascular endothelial growth factor (VEGF) inhibitors, etc. All of
      them have been unsuccessful in adding any survival advantage. DNA repair
      inhibitors, immunotherapies and anti-delta-like protein 3 (DLL3) antibody-drug
      conjugates have also been tested so far. This article aims to review the current
      literature and investigational approaches to improving clinical outcomes of SCLC.

PMID- 30209443
TI  - Deprescribing medications in older people: a narrative review.
AB  - In the aging population, the process of medication prescribing and management is
      likely to be complex and challenging. Polypharmacy and inappropriate medication
      use are more prevalent among older people and are associated with geriatric
      syndromes, reduced cognitive and functional outcomes, and increased mortality.
      Deprescribing is the process of planned and supervised tapering or safe
      withdrawal of potentially inappropriate medication that can cause harm, or is no
      longer indicated or beneficial to the current therapy. The purpose of
      deprescribing is to reduce inappropriate polypharmacy, medication burden and
      harm, and to improve patient health-related outcomes. Deprescribing is best
      performed by reducing medicines one at a time, and the whole process requires
      careful assessment, effort, commitment and time. Deprescribing should be
      considered after careful assessment of the patient's overall health, therapeutic
      goals, medication adherence to current treatment regimen and willingness to
      deprescribe the medicine. Many medications can be safely removed; to successfully
      achieve this, the process of deprescribing should follow an evidence-based,
      patient-centered and team-based approach involving both the healthcare
      professionals and the patient/caregivers to effectively reduce inappropriate
      medication use.

PMID- 30209444
TI  - Joint 24th Medicines for Europe and 21st International Generic and Biosimilars
      Association (IGBA) Annual Conference (June 13-15, 2018 - Budapest, Hungary).
AB  - The joint 24th Medicines for Europe and 21st International Generic and
      Biosimilars Association (IGBA) Annual Conference brought together key industry
      leaders and more than 200 participants in Budapest, Hungary, to discuss both
      challenges and opportunities for the global generic, biosimilar and value added
      medicines industries. Challenges relating to sustainability were debated with key
      experts, who shared perspectives on topics such as medicines shortages, use of
      data, Brexit, international regulatory cooperation, the E.U. Falsified Medicines
      Directive (FMD) and the potential impact of antimicrobial resistance. European
      industry leaders outlined the period of intense preparations needed to ensure
      compliance by the early 2019 milestones for the FMD and Brexit. The conference
      also anticipated exciting opportunities for the industry and broadly welcomed the
      European Commission's legislative proposal for a (long-awaited and much
      discussed) E.U. Supplementary Protection Certificate manufacturing waiver.
      Medicines for Europe and IGBA are committed to supporting and strengthening such
      policy initiatives aimed at boosting European competitiveness, increasing
      investments in R+D for biosimilar medicines, and most importantly, delivering
      faster access to medicines for patients. The importance of not forgetting that
      the ultimate aim of the industry was to facilitate patient access to necessary
      medicines was stressed throughout the conference. As the conference took place in
      Hungary, Laszlo Gyorgy (State Secretary for Economic Strategy and Regulation at
      the Ministry of Innovation and Technology) spoke about the role of technology
      innovation and access to medicines in the country and the role of his ministry.
      He indicated that the primary goal of the newly established ministry was to
      maintain and improve decent living conditions in the light of aging populations
      and enhance the competitiveness of the pharmaceutical industry, "which plays a
      decisive role in the Hungarian economy."

PMID- 30209445
TI  - Rational design of multi-stimuli-responsive gold nanorod-curcumin conjugates for
      chemo-photothermal synergistic cancer therapy.
AB  - In recent decades, the development of novel photorelated nanomedicines as precise
      cancer nanotheranostics has received extensive attention. However, strategies
      aimed at integrating various stimuli-responsive multimodal therapies are needed.
      Herein, we developed a novel system for combined plasmonic photothermal therapy
      (PPTT) and chemotherapy using the tumor microenvironment and near-infrared (NIR)
      responsive gold nanorod-drug conjugates (Au NR@Curcumin). To synthesize this
      conjugate, the alkanethiol aliphatic acid (11-mercaptoundecanoic acid, MUA) group
      was covalently linked to curcumin via an ester bond. MUA-curcumin conjugates and
      thiol-end-functionalized PEG were used to replace cetyltrimethylammonium bromide
      (CTAB) while modifying the surface of the Au NRs. The size, zeta potential and
      shape were measured to characterize Au NR@Curcumin. The release of curcumin from
      Au NR@Curcumin was achieved by the cleavage of the esterase-labile ester bond in
      the tumor microenvironment which was enriched in esterase. Under NIR irradiation,
      the release of curcumin from Au NR@Curcumin was accelerated, caused by the
      excellent photothermal effect of the Au NRs. The antitumor effects of Au
      NR@Curcumin were tested on A549 human lung cancer cells, KB human oral epidermoid
      carcinoma cells and HepG2 human liver carcinoma cells. The ability of the
      nanosystem to efficiently control the drug release responding to NIR laser
      irradiation and act as an outstanding hyperthermia agent was demonstrated. The
      systematic mechanistic elucidation of the tumor cell killing effect is achieved
      by inducing apoptosis and the arrest of the cell cycle in the treated cells. The
      combination of photothermal therapy and chemotherapy using the compact Au
      NR@Curcumin system showed a strong in vivo anticancer effect superior to that of
      either of the two treatments alone due to a synergistic effect. These results
      suggest that Au NR@Curcumin is a novel and promising photoablation agent that may
      be used for cancer nanotheranostics.

PMID- 30209446
TI  - Opening two benzene rings on trichalcogenasumanenes toward high performance
      organic optical-limiting materials.
AB  - Two flanking benzene rings on trichalcogenasumanenes (1a/1b) were opened upon
      oxidation, and the successive ring reconstruction afforded donor-acceptor type
      polycycles containing diimide units (3a/3b). 3a and 3b show excellent optical
      limiting properties superior to C60.

PMID- 30209448
TI  - Metallaaromatic biaryl atropisomers.
AB  - Synthesis of stable irida-binaphthyl and -phenanthryl complexes, the first
      examples of metallaaromatic biaryl atropisomers, has been achieved. The
      combination of experimental and theoretical studies revealed that the nature of
      these systems is comparable to that of well-known 1,1'-binaphthalene both in
      terms of aromaticity and atropisomerism.

PMID- 30209447
TI  - Temperature-programmed desorption studies of NH3 and H2O on the RuO2(110)
      surface: effects of adsorbate diffusion.
AB  - Temperature-programmed desorption (TPD) is one of the most straightforward
      surface science experiments for the determination of the thermodynamic and
      kinetic parameters of a reaction. In our previous study (J. Phys. Chem. C, 2013,
      117, 6136-6142), we proposed a model combining DFT methods with microkinetics to
      investigate the TPD spectra of NH3 and H2O on the RuO2(110) surface. Although our
      model predicted both the physisorption and chemisorption peaks of both adsorbates
      in agreement with the experimental TPD spectra, it failed to explain the region
      between the physisorption and chemisorption areas and underestimated the
      intensity of the adsorbate in these areas. Hence, to improve our model, in this
      study, we considered the diffusion of adsorbates from the sub-monolayer to the
      second layer. Accordingly, we simulated the TPD spectra of both NH3 and H2O on
      the RuO2(110) surface using condensation approximation. Our results indicate that
      the diffusion barriers of the adsorbates at high coverage are smaller than their
      direct desorption energies. Hence, the diffusion of the adsorbates to the second
      layer from the sub-monolayer at higher coverage is kinetically favorable, which
      then desorb directly even at low temperatures. Furthermore, the simulated TPD
      spectra clearly depict the previous experimental results of both adsorbates after
      considering the diffusion.

PMID- 30209449
TI  - Aligning self-assembled perylene bisimides in a magnetic field.
AB  - Photoconductive self-assembled 1D structures can be formed by perylene bisimides.
      These structures are generally randomly orientated, limiting their applications
      as conductive wires. Here, we show that magnetic fields can be used to create
      highly aligned, directionally-dependent thin films. This approach leads to well
      aligned structures over large areas.

PMID- 30209450
TI  - Strong electron-phonon interaction retarding phonon transport in superconducting
      hydrogen sulfide at high pressures.
AB  - Realistic representation of quantum interactions between electrons and phonons is
      crucial to uncovering the fundamental origin of superconductivity and predicting
      superconductors with a high transition temperature (Tc). We study the influence
      of the intrinsic electron-phonon interaction (EPI) on the phonon transport of
      superconducting hydrogen sulfide at high pressures, and its variation under an
      external magnetic field using all-electron first-principles calculations. High
      pressure greatly shortens interatomic distances, modifies the Fermi surface with
      sharp variation around sulfide atoms and leads to a strong EPI. Such a strong EPI
      substantially broadens the linewidths of major heat-carrying phonons and induces
      discontinuity, the so-called Kohn anomalies, in the phonon dispersions. In the
      superconducting state, the strong EPI competes with the weakened phonon-phonon
      interactions and induces a local peak in lattice thermal conductivity well below
      Tc. Under an external magnetic field, the reduced electron density around the
      Fermi surface leads to a slightly decreased EPI and Tc, which is consistent with
      previous experimental observation. The results gained from this work help us to
      understand the quantum behaviors of electrons and phonons and the influence of
      their interaction on the phonon transport of high-Tc superconductors.

PMID- 30209451
TI  - Boron triel bonding: a weak electrostatic interaction lacking electron-density
      descriptors.
AB  - In an effort to describe pi-hole interactions, we undertook accurate high
      resolution X-ray diffraction analyses of single crystals of 1,4-dinitrobenzene, a
      co-crystal of cis-tartaric acid and bis-pyridine N-oxide and the hydrochloride of
      B-4-pyridinylboronic acid. We selected these three compounds owing to the pi-hole
      accessibility features that the sp2 hybridized B, C and N atoms provide, thus
      allowing us to compare the fundamental characteristics of pi-hole interactions
      using Bader's Atom in Molecules (AIM) theory. This particular study required
      extremely accurate experimental diffraction data, because the interaction of
      interest is weak. As shown by the experimental charge density maps of the -YO2 (Y
      = B, C, N) units, we assign the depletion of electron-density present in the
      central boron, carbon and nitrogen atoms (electrophilic pi-holes) as the main
      origin for the establishment of intermolecular Lewis acid-Lewis base attractive
      interaction with complementary electron-rich regions. Unexpectedly, the Bader's
      analyses of both experimentally and theoretically calculated charge distribution
      maps for the solid involving the - BO2H2 group do not show the presence of bond
      paths, neither of the bond critical points, between the interacting electron rich
      sites and the boron or carbon atoms featuring the electron hole. In contrast,
      these topological descriptors of chemical interactions for the AIM theory were
      easily located in the solid-state structures of the compounds involving the
      carboxylic and the nitro groups.

PMID- 30209453
TI  - Probing charge transfer dynamics in a single iron tetraphenylporphyrin dyad
      adsorbed on an insulating surface.
AB  - Although the dynamics of charge transfer (CT) processes can be probed with
      ultimate lifetime resolution, the inability to control CT at the nanoscale is one
      of the most important roadblocks to revealing some of its deep fundamental
      aspects. In this work, we present an investigation of CT dynamics in a single
      iron tetraphenylporphyrin (Fe-TPP) donor/acceptor dyad adsorbed on a CaF2/Si(100)
      insulating surface. The tip of a scanning tunneling microscope (STM) is used to
      create local ionic states in one fragment of the dyad. The CT process is
      monitored by imaging subsequent changes in the neighbor acceptor molecule and its
      efficiency is mapped, revealing the influence of the initial excited state in the
      donor molecule. In the validation of the experiments, simulations based on
      density functional theory show that holes have a higher donor-acceptor CT rate
      compared to electrons and highlight a noticeable initial state dependence on the
      CT process. We leverage the unprecedented spatial resolution achieved in our
      experiments to show that the CT process in the dyad is governed via molecule
      molecule coherent tunneling with negligible surface-mediated character.

PMID- 30209452
TI  - A DNA-nanoparticle actuator enabling optical monitoring of nanoscale movements
      induced by an electric field.
AB  - Merging biological and non-biological matter to fabricate nanoscale assemblies
      with controllable motion and function is of great interest due to its potential
      application, for example, in diagnostics and biosensing. Here, we have
      constructed a DNA-based bionanoactuator that interfaces with biological and non
      biological matter via an electric field in a reversibly controllable fashion. The
      read-out of the actuator is based on motion-induced changes in the plasmon
      resonance of a gold nanoparticle immobilized to a gold surface by single stranded
      DNA. The motion of the gold nanoparticle and thus the conformational changes of
      the DNA under varying electric field were analyzed by dark field spectroscopy.
      After this basic characterization, another actuator was built utilizing hairpin
      DNA coated gold nanoparticles, where the hairpin-DNA induced discrete transitions
      between two specific open-loop and folded-loop states. These two states and the
      transition dynamics between them were clearly visible in the actuator behavior.
      The demonstrated nanoactuator concept could be readily extended to inspection of
      conformational changes of other biomolecules as well. Besides, this concept
      enables other possibilities in applications like surface-enhanced Raman
      spectroscopy and fluorescence enhancement, since the specific wavelength of the
      plasmon resonance of the actuator can be tuned by the external voltage.

PMID- 30209455
TI  - Recent developments and applications of cyanamides in electrophilic cyanation.
AB  - Nitriles are widely present in various natural products, pharmaceuticals,
      agrochemicals and dyes. In addition, nitriles are an essential building unit in
      organic synthesis, which can be readily converted into numerous functional
      groups. Consequently, the development of new methods for the synthesis of
      nitriles has gained significant attention in organic synthesis. Over the past few
      decades, particularly, aryl nitriles were obtained by the cyanation of aryl
      halides employing metallic/nucleophilic cyano group sources. However, these
      methods suffer from high catalyst loading and toxic cyano sources. To overcome
      these problems, various organic cyano group sources have been explored in recent
      years for the synthesis of nitriles. Among them, cyanamides have attracted
      significant attention due to their ready availability, ease of handling, and
      nontoxic and inexpensive nature. In this review, we have summarized the recent
      developments and applications of cyanamides in the electrophilic cyanation of
      various nucleophiles.

PMID- 30209454
TI  - A fast and powerful swimming microrobot with a serrated tail enhanced propulsion
      interface.
AB  - We demonstrate the use of a swimming microrobot with a serrated tail in the
      propulsion region to enhance reaction interfaces. A 3D printed tail with multiple
      catalytic channels and nanointerfaces could reinforce the microrobot, allowing it
      to reach swimming speeds of ~1 mm s-1 and enabling it to transport objects with a
      weight 6500 times that of itself. This research represents a new concept in
      swimming microrobot design and is expected to benefit a wide range of engineering
      fields.

PMID- 30209456
TI  - Catalyst-free synthesis of alpha-thioacrylic acids via cascade thiolation and 1,4
      aryl migration of aryl alkynoates at room temperature.
AB  - A simple and facile catalyst-free method for the construction of alpha
      thioacrylic acids has been developed from readily-available aryl alkynoates and
      thiols at room temperature. Various alpha-thioacrylic acids could be conveniently
      and efficiently obtained in moderate to good yields via cascade thiolation and
      1,4-aryl migration of aryl alkynoates in the absence of any catalyst and
      additive.

PMID- 30209457
TI  - Hydrogen evolution reaction (HER) on Au@Ag ultrananoclusters as electro
      catalysts.
AB  - We propose and investigate computationally Ag-Au subnanometer clusters as
      catalysts for the hydrogen evolution reaction (HER). Focusing on Ag12Au, we
      conduct a complete first-principles study of the HER process on this Au@Ag
      ultrananocatalyst. After determining the hydrogen-saturated resting state under
      standard conditions as Ag12AuH11, HER reaction energies and barriers are
      predicted also including solvent effects using both implicit and explicit models.
      We find that Ag12Au is a good candidate as a HER catalyst, with good stability
      and an overall reaction energy barrier of 0.89 eV as an upper bound. We also draw
      indications for the design of HER subnanometer catalysts.

PMID- 30209458
TI  - Low-temperature wafer-scale synthesis of two-dimensional SnS2.
AB  - Research on two-dimensional (2D) metal dichalcogenides is rapidly expanding owing
      to their unique characteristics that do not exist in bulk materials. The
      industrially compatible development of these emerging materials is indispensable
      to facilitate the transition of 2D metal dichalcogenides from the research stage
      to the practical industrial application stage. However, an industrially relevant
      method, i.e., the low-temperature synthesis of wafer-scale, continuous, and
      orientation-controlled 2D metal dichalcogenides, still remains a significant
      challenge. Here, we report the low-temperature (<=350  degrees C) synthesis of
      uniform and continuous n-type SnS2 thin films via the combination of atomic layer
      deposition (ALD) of tin oxides and subsequent sulfurization. Well-crystallized
      and aligned SnS2 layers parallel to the substrate are demonstrated through the
      phase engineering of the ALD-grown tin oxide and the substrate surface. The
      additional H2S plasma treatment at 300  degrees C leads to the formation of
      stoichiometric SnS2. The formation of conformal SnS2 layers over a three
      dimensional undulating hole structure is confirmed, which reveals the potential
      for applications beyond the planar structured architecture. The present results
      could be a step toward the realization of 2D metal dichalcogenides in industry.

PMID- 30209459
TI  - Electrochemical sensors based on molecularly imprinted polymers on Fe3O4/graphene
      modified by gold nanoparticles for highly selective and sensitive detection of
      trace ractopamine in water.
AB  - A novel molecular imprinting polymer (MIP)-based electrochemical senor,
      consisting of Fe3O4 nanobeads and gold nanoparticles on a reduced graphene oxide
      (RGO) substrate, was fabricated to detect ractopamine (RAC) in water using the
      reversible addition fragmentation chain transfer (RAFT) polymerization technique.
      The Au nanoparticles widely dispersed on RGO can significantly increase the
      response current for RAC detection in water, which is confirmed by cyclic
      voltammetry (CV), electrochemical impedance spectroscopy (EIS) and theoretical
      calculations. By means of the differential pulse voltammetry technique, the as
      prepared MIP-based electrode shows a dynamic linear range of 0.002 to 0.1 MUM
      with a correlation coefficient of 0.992 and a remarkably low detection limit of
      0.02 nM (S/N = 3). Additionally, the sensor exhibits high binding affinity and
      selectivity towards RAC with excellent reproducibility. Our study demonstrates
      the potential for the proposed electrochemical sensors in monitoring organic
      pollutants in water.

PMID- 30209460
TI  - Phase separation strategy to facilely form fluorescent [Ag2]2+/[Agm]n+ quantum
      clusters in boro-alumino-silicate multiphase glasses.
AB  - By adjusting the content of ZnF2-SrF2/ZnO-SrO, a series of SiO2-Al2O3-B2O3-Na2O
      ZnO/ZnF2-SrO/SrF2-Ag multiphase glasses was designed and prepared via a melt
      quenching method. Under a phase separation strategy, negatively charged
      tetrahedrons ([BO4]-, [ZnO4]2-, and [AlO4]-) can be generated to stabilize
      different silver species (Ag+ ions; [Ag2]2+ pairs; [Agm]n+ quantum clusters
      ([Agm]n+ QCs)) in B2O3-rich and ZnO-Al2O3 rich sub-phases. The B2O3-rich sub
      phase has a high solubility for Ag+ ions and [Agm]n+ QCs. The fluoride-rich phase
      shows a good ability to extract Na+ from the B2O3-rich sub-phase, significantly
      affects the solubility of Ag+ in the B2O3-rich sub-phase, and eventually
      determines the aggregation from Ag+ ions and Ag0 atom to [Agm]n+ QCs. The ZnO
      Al2O3-rich or ZnO-SiO2-rich (i.e. SiO2-rich in GZnOSrO) phase has a relatively
      high solubility for [Ag2]2+ pairs. The Ag+/[Ag2]2+/[Agm]n+ QC fluorescent centers
      were identified by spectroscopic analysis, where the fluorescence bands are
      located in the ultraviolet, green-white and orange spectral regions,
      respectively. The fluorescent quantum yield (QY) of the [Agm]n+ QCs can be
      improved to 55.7%, and the combination of these three luminescent centers can
      achieve white light emission.

PMID- 30209461
TI  - Mobilising ion mobility mass spectrometry for metabolomics.
AB  - Chromatography-based mass spectrometry approaches (xC-MS) are commonly used in
      untargeted metabolomics, providing retention time, m/z values and metabolite
      specific fragments, all of which are used to identify and validate an unknown
      analyte. Ion mobility-mass spectrometry (IM-MS) is emerging as an enhancement to
      classic xC-MS strategies, by offering additional ion separation as well as
      collision cross section (CCS) determination. In order to apply such an approach
      to a metabolomics workflow, verified data from metabolite standards is necessary.
      In this work we present experimental DTCCSN2 values for a range of metabolites in
      positive and negative ionisation modes using drift tube-ion mobility-mass
      spectrometry (DT-IM-MS) with nitrogen as the buffer gas. The value of DTCCSN2
      measurements for application in metabolite identification relies on a robust
      technique that acquires measurements of high reproducibility. We report that the
      CCS values found for 86% of metabolites measured in replicate have a relative
      standard deviation lower than 0.2%. Examples of metabolites with near identical
      mass are demonstrated to be separated by ion mobility with over 4% difference in
      DTCCSN2 values. We conclude that the integration of ion mobility into current LC
      MS workflows can aid in small molecule identification for both targeted and
      untargeted metabolite screening.

PMID- 30209462
TI  - Ruthenium-catalyzed tandem annulation/arylation for the synthesis of
      unsymmetrical bis(heteroaryl)methanes.
AB  - A new Ru-catalyzed tandem furan annulation/arylation strategy has been developed
      to afford unsymmetrical bis(heteroaryl)methanes by a reaction between propargyl
      amines and indoles. A series of bis(heteroaryl)methanes containing furan and
      indole as well as indole and imidazopyridine moieties have been synthesized in
      high yields. The reaction possibly proceeds through furan annulation followed by
      nucleophilic addition of indole.

PMID- 30209463
TI  - Effects of gamma radiation on the bioactivity of medicinal and aromatic plants:
      Mentha * piperita L., Thymus vulgaris L. and Aloysia citrodora Palau as case
      studies.
AB  - Irradiation is a feasible and safe decontamination technique, being applied to
      several types of foods including edible and medicinal plants. The aim of this
      study was to evaluate the effects of different gamma radiation doses (1, 5 and 10
      kGy) on the individual profile of phenolic compounds determined by HPLC-DAD
      ESI/MS, and the bioactive potential (cytotoxic, virucidal, and antimicrobial
      activities) of Aloysia citrodora Palau (lemon verbena), Mentha * piperita L.
      (peppermint) and Thymus vulgaris L. (thyme). The observed cytotoxic activity
      varied with the plant and with the applied dose, being higher in Thymus vulgaris
      irradiated with 10 kGy. The virucidal activity was also dependent on the
      radiation dose, but was preserved with irradiation treatment. Gamma rays had no
      effect on the antimicrobial activity of the studied plants. Otherwise, the
      effects of gamma radiation on the phenolic profile were heterogeneous, with an
      increase in some compounds and decrease in others, depending on the species and
      on the radiation dose.

PMID- 30209464
TI  - Structural characterization of self-assemblies of new omega-3 lipids:
      docosahexaenoic acid and docosapentaenoic acid monoglycerides.
AB  - The attractiveness of new omega-3 (omega-3) polyunsaturated fatty acid (PUFA)
      monoglycerides (MAGs) lies in the amphiphilic nature and the beneficial health
      effects as PUFA precursors in various disorders including cancer, pulmonary
      hypertension, and inflammatory diseases. For exploring the potential therapeutic
      applications of these new amphiphilic lipids, particularly as main lipid
      constituents in the development of nanocarriers for delivery of drugs and PUFAs,
      it is of paramount importance to gain insight into their self-assembly behavior
      on exposure to excess water. This work describes the structural characteristics
      of self-assemblies based on two newly synthesized MAGs, namely docosahexaenoic
      acid (MAG-DHA) and docosapentaenoic acid (MAG-DPA) monoglycerides, on exposure to
      excess water. We found that both lipids tend to form a dominant inverse hexagonal
      (H2) phase in excess water at 25  degrees C and a temperature-triggered
      structural transition to an inverse micellar solution (L2 phase) is detected
      similar to that recently reported (A. Yaghmur et al., Langmuir, 2017, 33, 14045
      14057) for eicosapentaenoic acid monoglyceride (MAG-EPA). An experimental SAXS
      structural evaluation study on the temperature-dependent behavior of these new
      monoglycerides is provided, and the effects of unsaturation degree and fatty acyl
      chain length on the self-assembled structural features in excess water and on the
      H2-L2 phase transition temperature are discussed. In addition, hexosomes
      stabilized by using the triblock copolymer F127 and the food-grade emulsifier
      citrem were investigated to gain insights into the effects of stabilizer and
      temperature on the internal nanostructure. These nanoparticles are attractive for
      use in the development of nanocarriers for delivering drugs and/or nutritional
      compounds as the beneficial health effects of omega-3 PUFA monoglycerides can be
      combined with those of loaded therapeutic agents or nutraceuticals.

PMID- 30209465
TI  - New gold pincer-type complexes: synthesis, characterization, DNA binding studies
      and cytotoxicity.
AB  - With the aim of assessing whether Au(iii) compounds with pincer type ligands
      might be utilized as potential antitumor agents, three new monofunctional Au(iii)
      complexes of the general formula [Au(N-N'-N)Cl]Cl2, where N-N'-N = 2,6-bis(5-tert
      butyl-1H-pyrazol-3-yl)pyridine (H2LtBu, 1), 2,6-bis(5-tert-butyl-1-methyl-1H
      pyrazol-3-yl)pyridine (Me2LtBu, 2) or 2,6-bis((4S,7R)-1,7,8,8-tetramethyl-4,5,6,7
      tetrahydro-1H-4,7-methanoindazol-3-yl)pyridine (Me2*L, 3) were synthesized. All
      complexes were characterized by elemental analysis, spectroscopic techniques (IR,
      UV-Vis, 1D and 2D NMR) and mass spectrometry (MALDI TOF MS). The chemical
      behavior of the complexes under physiological conditions was studied by UV-Vis
      spectroscopy, which showed that all compounds were remarkably stable and that the
      gold center remained in the 3+ oxidation state. The kinetics and the mechanism of
      the reaction of complexes 1-3 with guanine derivatives (i.e. guanosine (Guo) and
      guanosine-5'-monophosphate (5'-GMP)) and calf thymus DNA (CT DNA) were studied by
      stopped-flow spectroscopy. The three complexes displayed moderately different
      rate constants in their reactions with Guo, 5'-GMP and CT DNA, which can be
      explained by the steric hindrance and sigma-donicity of the methyl substituent on
      the bis-pyrazolylpyridine fragment in complexes 2 and 3. The measured enthalpies
      and entropies of activation (DeltaH? > 0, DeltaS? < 0) supported an associative
      mechanism for the substitution process. The interaction of the newly synthesized
      complexes 1-3 with CT DNA was investigated by UV-Vis and fluorescence
      spectroscopy, and also by viscosity measurements, which all indicated that
      complexes 1-3 bound to CT DNA with moderate binding affinity (Kb = 1.6-5.7 * 103
      M-1) and stabilized the duplex of CT DNA. Molecular docking indicated that
      complexes 1-3 interacted with DNA via intercalation. Complex 1 reduced the cell
      survival of all the investigated cell lines (A549, A375, and LS-174) with IC50
      values being up to 20 MUM. We have shown that 1 induced perturbations of the cell
      cycle and led to apoptosis in human melanoma A375 cells. Complex 1 also affected
      the level of reactive oxygen species (ROS) in the same cells. However, pre
      treatment of A375 cells with NAC (ROS scavenger) reversed the effect of 1 on
      their survival.

PMID- 30209466
TI  - Multimodal character of shear viscosity response in hydrogen bonded liquids.
AB  - The impact of supramolecular aggregate formation on the shear viscosity response
      of hydrogen bonded liquids was investigated. In particular, we study the shear
      mechanical response of several monoalcohols showing exponential and non
      exponential shape dielectric Debye-like relaxation. In addition to the structural
      relaxation, distinctive of the glass transition, and the terminal crossover to
      pure viscous flow, characteristic of simple liquid flow, systematic analysis of
      complex viscosity curves evidences the presence of an additional intermediate
      process between those two. While the recovery of pure viscous flow would reflect
      the complete relaxation of the hydrogen bonded aggregates the intermediate
      process correlates with the rotational dynamics of hydroxyl groups, potentially
      caused by the breaking of individual hydrogen bonds.

PMID- 30209467
TI  - A label-free and ultrasensitive electrochemical aptasensor for lead(ii) using a
      N,P dual-doped carbon dot-chitosan composite as a signal-enhancing platform and
      thionine as a signaling molecule.
AB  - Herein, a label-free and ultrasensitive electrochemical aptasensor for the
      determination of lead(ii) (Pb2+) was described. It was based on the application
      of a N,P dual-doped carbon dot-chitosan (N,P-CD-CS) composite as the signal
      molecule carrier and an aptamer (APT) as the specific binding probe for Pb2+ that
      were self-assembled on the surface of a gold electrode (GE). 6-Mercapto-1-hexanol
      (MCH) was used to block the nonspecific binding sites, and the electro-active
      molecule thionine (THi) was used as the signaling probe. The differential pulse
      voltammetry (DPV) response of THi at a rather low working potential of -0.17 V
      (vs. Ag/AgCl) was used to detect Pb2+. The electrochemical performances of the
      resulting modified electrode were investigated by cyclic voltammetry and
      electrochemical impedance spectroscopy. Under optimal experimental conditions,
      the modified electrode exhibited excellent DPV response depending on the
      concentration of Pb2+ in the 0.01 nM to 10 nM range. The limit of detection was
      3.8 pM (at S/N = 3). The modified electrode displayed good reproducibility and
      excellent stability. It was successfully applied for the determination of Pb2+ in
      real water samples.

PMID- 30209468
TI  - Correlation of drug-induced and drug-related ultra-high performance liquid
      chromatography-mass spectrometry serum metabolomic profiles yields discovery of
      effective constituents of Sini decoction against myocardial ischemia in rats.
AB  - Screening active constituents of traditional Chinese medicines (TCMs) is vital
      for lead compound discovery. Sini decoction (SND) is a well-known TCM formula for
      relieving myocardial ischemia (MI) in clinic. Due to complex nature, the
      effective compounds of SND are still unknown. In this study, a novel "system to
      system" strategy based on the correlation of drug-related and drug-induced ultra
      high performance liquid chromatography coupled with quadrupole-time-of-flight
      mass spectrometry (UHPLC-Q-TOFMS) serum metabolomic profiles was developed to
      discover bioactive compounds of SND against isoproterenol-induced MI. Thirteen
      SND-induced metabolites and 19 SND-related metabolites were identified by UHPLC-Q
      TOFMS coupled with S-plot and SUS-plot of orthogonal projection to latent
      structure-discriminant analysis (OPLS-DA) models, respectively. Canonical
      correlation analysis between the SND-induced and SND-related metabolites revealed
      that 12 compounds had strongly correlated relationship with the protective effect
      of SND on MI, and these compounds include isotalatizidine, songorine, fuziline,
      neoline, talatizamine, 14-acetyltalatizamine, liquiritigenin,
      benzoylmesaconitine, isoliquiritin, benzoylaconitne, benzoylhypaconitine and 6
      gingerol. Combination functional enrichment analysis and network topology
      analysis revealed that the targeted metabolic pathways of these correlated
      compounds were involved in valine, leucine and isoleucine biosyntheses,
      tryptophan metabolism, glycerophospholipid metabolism and sphingolipid
      metabolism. The results demonstrated that the "system to system" strategy may be
      a high-throughput method to discover potentially effective compounds from TCMs.

PMID- 30209469
TI  - Modeling of solid-liquid interfaces using scaled charges: rutile (110) surfaces.
AB  - Electronic continuum correction (ECC) has been proven to bring significant
      improvement in the modeling of interactions of ions (especially multivalent) in
      aqueous solutions. We present a generalization and the first application of this
      approach to modeling solid-liquid interfaces, which are omnipresent in physical
      chemistry, geochemistry, and biophysics. Scaling charges of the top layer of
      surface atoms makes the existing solid models compatible with the ECC models of
      ions and molecules, allowing the use of modified force fields for a more accurate
      investigation of interactions of various metal and metal-oxide surfaces with
      aqueous solutions, including complex biomolecules and multivalent ions. We have
      reparametrized rutile (110) models with different surface charge densities (from
      0 to -0.416 C m-2) and adopted/developed scaled charge force fields for ions,
      namely Na+, Rb+, Sr2+, and Cl-. A good agreement of the obtained molecular
      dynamics (MD) data with X-ray experiments and previously reported MD results was
      observed, but changes in the occupancy of various adsorption sites were observed
      and discussed in detail.

PMID- 30209470
TI  - The double exciton state of conjugated chromophores with strong diradical
      character: insights from TDDFT calculations.
AB  - A peculiar characteristic of open-shell singlet diradical molecules is the
      presence of a double exciton state (H,H -> L,L) among low lying excited states.
      Recent high-level quantum-chemical investigations including a static and dynamic
      electron correlation have demonstrated that this state can become the lowest
      singlet excited state, a diagnostic fingerprint of the diradical system. Here we
      investigate the performance of less computationally demanding TDDFT calculations
      by employing two approaches: the spin-flip TDDFT scheme and TD calculations based
      on unrestricted broken symmetry antiparallel-spin reference configuration
      (TDUDFT). The calculations are tested on a number of recently synthesized, large
      conjugated systems displaying from moderate to large diradical character and
      showing experimental trace of the double exciton state. We show that spin-flip
      (SF) TDB3LYP calculations in the collinear approximation generally underestimate
      the excitation energy of the double exciton state. When the molecule displays a
      strong diradical character, the unrestricted antiparallel-spin reference
      configuration of TDUDFT calculations is characterized by strongly localized
      frontier molecular orbitals. We show that under these conditions the double
      exciton state is captured by TDUB3LYP calculations since it is described by
      singly excited configurations and its excitation energy can be accurately
      predicted. Owing to the improved description of the ground state, also the
      excitation energy of the single exciton H -> L state generally improves at the
      TDUB3LYP level. With regard to the double exciton state, SF TDB3LYP performs
      slightly better for small to medium diradical character while a large diradical
      character (and strong orbital localization) is a prerequisite for the success of
      TDUB3LYP calculations whose quality otherwise deteriorates.

PMID- 30209471
TI  - Toward the total synthesis of patellazole B: synthesis of an advanced C1-C25
      fragment corresponding to the macrocyclic skeleton.
AB  - The patellazoles are a family of complex marine macrolides that exhibit potent
      cytotoxicity against cancer cell lines. However, despite extensive
      characterisation efforts, their full stereochemical assignment has remained
      elusive. We report our approach towards the synthesis-enabled structural
      elucidation of patellazole B (4), a 24-membered macrolide with 16 stereocentres
      and a signature thiazole-containing side chain. Our plan hinges upon isolating
      the unknown stereocentres into a single C20-C25 fragment to facilitate the
      flexible assembly of various possible diastereomers of an advanced C1-C25
      fragment. Towards this end, a highly convergent and modular synthesis of one
      candidate diastereomer 37, corresponding to the patellazole B macrocyclic
      skeleton, has been achieved based on the strategic application of
      stereocontrolled aldol methodology, combined with Suzuki and Heck cross-coupling
      reactions.

PMID- 30209472
TI  - Short-term urea cycle inhibition in rat liver cells induced by polyethylene
      glycol.
AB  - Polyethylene glycol (PEG) is widely used in the biomedical field due to its
      outstanding properties. There are plenty of reports on the safety of PEG, but
      they are mostly restricted to its pharmacokinetic behaviour and pathological
      effect in vivo, and fail to elucidate its biological effects on cells at the
      molecular level. Consequently, here we illuminate the biological effect of PEG on
      a specific cellular pathway. We found that PEG could induce short-term urea cycle
      inhibition in rat liver cells in vitro without damaging the mitochondria and
      cells, which was proven to be an adaptive and reversible response to PEG at the
      molecular level. PEG could also induce a transient hepatic stress response in
      vivo, which was closely related with the urea cycle disorder. As a mechanistic
      study on the interactions between a synthetic biomedical polymer and cells at the
      molecular level, our work provides novel insights into the biological effects of
      polymers on a cellular system and is fundamental to the development of biomedical
      polymers.

PMID- 30209473
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
      huperphlegmine A from Huperzia phlegmaria.

PMID- 30209474
TI  - Current reversals of active particles in time-oscillating potentials.
AB  - Rectification of interacting active particles is numerically investigated in a
      two-dimensional time-oscillating potential. It is found that the oscillation of
      the potential and the self-propulsion of active particles are two different types
      of nonequilibrium driving, which can induce net currents with opposite
      directions. For a given asymmetry of the potential, the direction of the
      transport is determined by the competition of the self-propulsion and the
      oscillation of the potential. There exists an optimal oscillating angular
      frequency (or self-propulsion speed) at which the average velocity takes its
      maximal positive or negative value. Remarkably, when the oscillation of the
      potential competes with the self-propulsion, the average velocity can change
      direction several times due to the change in the oscillating frequency.
      Especially, particles with different self-propulsion velocities will move in
      opposite directions and can be separated. Our results provide a novel and
      convenient method for controlling and manipulating the transport (or separation)
      of active particles.

PMID- 30209475
TI  - Genomics-driven discovery of a linear lipopeptide promoting host colonization by
      endofungal bacteria.
AB  - The rice seedling blight fungus Rhizopus microsporus weakens or kills plants by
      means of a potent toxin produced by endobacteria (Burkholderia rhizoxinica) that
      live within the fungal hyphae. The success of the highly attuned microbial
      interaction is partly based on the bacteria's ability to roam and re-colonize the
      fungal host. Yet, apart from the toxin, chemical mediators of the symbiosis have
      remained elusive. By genome mining and comparison we identified a cryptic NRPS
      gene cluster that is conserved among all sequenced Rhizopus endosymbionts.
      Metabolic profiling and targeted gene inactivation led to the discovery of a
      novel linear lipopeptide, holrhizin A, which was fully characterized. Through in
      vitro and in vivo assays we found that holrhizin acts (A) as a biosurfactant to
      reduce surface tension, (B) influences the formation of mature biofilms and thus
      cell motility behavior that ultimately supports the bacterial cells to (C)
      colonize and invade the fungal host, consequently supporting the re-establishment
      of the exceptional Burkholderia-Rhizopus symbiosis. We not only unveil structure
      and function of an linear lipopeptide from endofungal bacteria but also provide a
      functional link between the symbiont's orphan NRPS genes and a chemical mediator
      that promotes bacterial invasion into the fungal host.

PMID- 30209476
TI  - Molecules mimicking atoms: monomers and dimers of alkali metal solvated electron
      precursors.
AB  - Tetra-amino lithium and sodium complexes M(NH3) (M = Li, Na) have one or two
      electrons that occupy diffuse orbitals distributed chiefly outside the M(NH3)
      core. The lowest-energy 1s, 1p, and 1d orbitals follow Aufbau principles found
      earlier for beryllium tetra-ammonia complexes. Two ground state M(NH3)4 complexes
      can bind covalently by coupling their 1s1 electrons into a sigma-type molecular
      orbital. The lowest excited states of the [M(NH3)4]2 species are obtained by
      promoting one or two electrons from this sigma to other bonding or anti-bonding
      sigma and pi-type molecular orbitals. The electronic structure of solvated
      electron precursors provides insights into chemical bonding between super-atomic
      species that are present in concentrated alkali-metal-ammonia solutions.

PMID- 30209477
TI  - Recent advances in beta-lactam synthesis.
AB  - During the past century, beta-lactams have been identified as the core of
      penicillin and since then several strategies have been developed for their
      synthesis. Traditional methods for beta-lactam synthesis usually involved amide
      bond formation and the Staudinger reaction. In recent years, by the advancement
      of photo- and transition metal-catalysis, several new methods have been reported
      for beta-lactam synthesis. For instance: ligand assisted metal catalyzed C-H
      activation/intermolecular oxidative amidation draws attention for beta-lactam
      synthesis. In this review we introduce methods for beta-lactam synthesis and
      present newly developed reactions. We approach the synthesis of beta-lactams
      according to different retro synthesis strategies.

PMID- 30209478
TI  - Direct C-4 alkylation of quinazoline N-oxides with ethers via an oxidative cross
      coupling reaction under metal-free conditions.
AB  - A novel and efficient protocol for the direct C-4 alkylation of quinazoline-3
      oxides via radical oxidative coupling between quinazoline 3-oxides and ethers in
      the presence of TBHP was developed. The reaction proceeded smoothly under metal
      free conditions, which provided quinazoline-containing heterocyclic molecules in
      moderate to good yields.

PMID- 30209479
TI  - Breakdown of Hooke's law at the nanoscale - 2D material-based nanosprings.
AB  - A helical spring is one of the fundamental mechanical elements commonly used
      throughout human history, whose deformation characteristic is well described by
      Hooke's law. Based on in silico studies, this work reported a novel structural
      transition from a homogeneous morphology to an inhomogeneous configuration in the
      normal helical nanospring (NS) for the first time, which provides rigorous proof
      for the "breakdown of Hooke's law" at the nanoscale. Theoretical analyses and
      numerical results show that the transition is expected to occur in a wide range
      of two-dimensional (2D) material based normal helical NSs, and the driving
      mechanism is the interlayer van der Waals (vdW) interactions. A series spring
      model is established to describe this transition phenomenon by considering the
      elastic deformation energy and interlayer interactions, which explicitly
      illustrates the competition between the surface energy and the elastic constant
      in controlling such a structural transition. It is expected that the structural
      transition is strictly limited to the nanoscale system, where the interlayer
      interactions exert significant influence on its mechanical properties. This study
      provides a comprehensive understanding of the non-Hookean behavior of NSs, and
      sheds light on their applications in micro- and nanomachines or mechanical
      systems, such as nanoelectromechanical systems, nanorobots or soft machines.

PMID- 30209480
TI  - Mutated variants of squalene-hopene cyclase: enzymatic syntheses of triterpenes
      bearing oxygen-bridged monocycles and a new 6,6,6,6,6-fusded pentacyclic
      scaffold, named neogammacerane, from 2,3-oxidosqualene.
AB  - Squalene-hopene cyclase (SHC) catalyzes the conversion of acyclic squalene
      molecule into a 6,6,6,6,5-fused pentacyclic hopene and hopanol. SHC is also able
      to convert (3S)-2,3-oxidosqualene into 3beta-hydroxyhopene and 3beta
      hydroxyhopanol and can generate 3alpha-hydroxyhopene and 3alpha-hydroxyhopanol
      from (3R)-2,3-oxidosqualene. Functional analyses of active site residues toward
      the squalene cyclization reaction have been extensively reported, but
      investigations of the cyclization reactions of (3R,S)-oxidosqualene by SHC have
      rarely been reported. The cyclization reactions of oxidosqualene with W169X,
      G600F/F601G and F601G/P602F were examined. The variants of the W169L generated
      new triterpene skeletons possessing a 7-oxabicyclo[2.2.1]heptane moiety (oxygen
      bridged monocycle) with (1S,2S,4R)- and (1R,2S,4S)-stereochemistry, which were
      produced from (3R)- and (3S)-oxidosqualenes, respectively. The F601G/P602F double
      mutant also furnished a novel triterpene, named neogammacer-21(22)-en-3beta-ol,
      consisting of a 6,6,6,6,6-fused pentacyclic system, in which Me-29 at C-22 of the
      gammacerane skeleton migrated to C-21. We propose to name this novel scaffold
      neogammacerane. The formation mechanisms of the enzymatic products from 2,3
      oxidosqualene are discussed.

PMID- 30209481
TI  - n- and p-type ohmic contacts at monolayer gallium nitride-metal interfaces.
AB  - Recently, two-dimensional (2D) gallium nitride (GaN) was experimentally
      fabricated, and has promising applications in next-generation electronic and
      optoelectronic devices. A direct contact with metals to inject the carrier is
      often required for potential 2D GaN devices. Herein, the first systematic study
      on the interface properties of monolayer (ML) planar and buckled GaN with
      different metal electrodes (Al, Ti, Ag, Au, Sc, and Pt) in a field-effect
      transistor framework is presented using first-principles energy band calculations
      and quantum transport simulations. Because of moderate Fermi level pinning
      (electron pinning factor S = 0.63), ML planar GaN and the Ag electrode form an n
      type lateral Schottky contact, while ML planar GaN and Ti, Al, and Au electrodes
      form a p-type lateral Schottky contact. The ML buckled GaN, Ag, Al, Ti, and Sc
      electrodes form a p-type lateral Schottky contact as a result of Fermi level
      pinning with a hole pinning factor of S = 0.75. Notably, a highly desirable n
      type/p-type lateral ohmic contact is formed at the lateral interface of the ML
      planar GaN and Sc/Pt electrodes, and a p-type lateral ohmic contact is formed at
      the lateral interface of the ML buckled GaN and Pt/Au electrodes. Therefore, a
      low resistance contact can be realized in ML planar and buckled GaN devices.

PMID- 30209482
TI  - tert-Butyl nitrite mediated nitrogen transfer reactions: synthesis of
      benzotriazoles and azides at room temperature.
AB  - A conversion of o-phenylenediamines into benzotriazoles was achieved at room
      temperature using tert-butyl nitrite. The optimized conditions are also well
      suited for the transformation of sulfonyl and acyl hydrazines into corresponding
      azides. This protocol does not require any catalyst or acidic medium. The desired
      products were obtained in excellent yields in a short span of time.

PMID- 30209483
TI  - Simple and rational design of a polymer nano-platform for high performance of HCV
      related miR-122 reduction in the liver.
AB  - microRNA-122 (miR-122) is a kind of non-coding RNA expressed specifically in the
      liver and accumulating evidence elucidates its relationship with HCV virus
      replication. The utilization of anti-miRNA oligonucleotide (antimiR) offers
      tremendous potential for future HCV infection therapy. However, multiple existing
      problems, such as targeting and stability, impede in vivo application of antimiR.
      To overcome them, we synthesized monomethoxy (polyethylene glycol)-poly (d,l
      lactide-co-glycolide)-poly (l-lysine) (mPEG-b-PLGA-b-PLL) materials to deliver
      miR-122 antagomir (AN), and formed stable and well-distributed AN-loaded mPEG-b
      PLGA-b-PLL nanoparticles (NP-AN). NP-AN showed a high degree of miR-122
      inhibition after 72 h in vitro. In vivo results showed an NP-AN "leak" through a
      hepatic sinusoid to reach hepatocytes and over 90% reduction of miR-122 after
      being injected with NP-AN for 72 h. Besides, the inhibition of miR-122 lasted for
      28 days with limited dosage in vivo. This study strongly suggests that the
      silencing of miR-122 was enhanced and the reduction of miR-122 expression could
      be extended by utilizing an mPEG-b-PLGA-b-PLL nano-platform, which potentially
      facilitate further studies on miRNA function loss and related RNAi therapy for
      HCV infection.

PMID- 30209484
TI  - Novel self-adaptive boat-shaped complexes with a tetraphosphine ligand.
AB  - A series of novel boat-shaped host-guest complexes were designed and synthesized
      by the combination of a new calixarene fragment-based tetraphosphine ligand L
      with group 11 metal salts Cu(MeCN)4ClO4 and AgNO3 in a self-assembly process, and
      by the following anion exchange reactions of complex 1 with sodium p
      toluenesulfonate, AcONa, PhCO2Na and sodium 9-anthrylcarboxylate. The host with a
      novel boat-shaped cavity is capable of self-adaptive encapsulation of various
      anions of different sizes through M(i)-O coordinations and CHpi interactions
      between the host and guest anion. The DFT calculations confirmed that the CHpi
      interaction played a vital role in the self-adaptive phenomenon in complexes 4-6.

PMID- 30209491
TI  - The adsorption of alcohols on strained Pt3Ni(111) substrates: a density
      functional investigation within the D3 van der Waals correction.
AB  - Experimental and theoretical studies have suggested the use of strain effects to
      design efficient catalysts for direct alcohol fuel cells. However, our atomistic
      understanding of the adsorption of alcohols on strained transition-metal (TM)
      catalysts is still far from satisfactory. Here, we report an ab initio
      investigation based on density functional theory within the van der Waals D3
      correction to explore the adsorption properties of methanol, ethanol and glycerol
      on Pt3Ni(111) alloys under different conditions. For that, we selected five TM
      substrates, namely, (i) Ni(111), (ii) Pt12Ni4/Pt12Ni4/Ni(111) (compressive
      strain), (iii) Pt16/Pt8Ni8/Pt3Ni(111) (without strain), (iv) Pt16/Pt8Ni8/Pt(111)
      (tensile strain) and (v) Pt(111). As expected, the physical and chemical
      properties of the Pt3Ni thin-layers are affected by the strain induced by the
      underlayer TM substrate, and hence, we can tune the adsorption properties of
      alcohols. In general, the magnitude of the alcohol adsorption energy increases in
      the following order Pt16/Pt8Ni8/Pt3Ni(111) < Pt16/Pt8Ni8/Pt(111) <
      Pt12Ni4/Pt12Ni4/Ni(111), which correlates with the d-band center and the
      effective charge on the adsorption sites, i.e., the coulombic contribution plays
      an important role in the adsorption. Structural and electronic density analyses
      indicate that, upon adsorption, the O-H and C-H bonds weaken and their breaking
      should be the first steps in the decomposition of alcohols. From the Bader charge
      analysis, we found that the TM atom directly below the bonding O loses charge to
      neighboring atoms, which polarizes the surface and changes the substrate work
      function. Although a significant enhancement of energetic and structural
      properties was found, the addition of the D3 correction does not change our
      qualitative results except for improving the dependence of the adsorption energy
      with the alcohol size.

PMID- 30209490
TI  - Quantum dot-sensitized solar cells.
AB  - Quantum dot-sensitized solar cells (QDSCs) have emerged as a promising candidate
      for next-generation solar cells due to the distinct optoelectronic features of
      quantum dot (QD) light-harvesting materials, such as high light, thermal, and
      moisture stability, facilely tunable absorption range, high absorption
      coefficient, multiple exciton generation possibility, and solution processability
      as well as their facile fabrication and low-cost availability. In recent years,
      we have witnessed a dramatic boost in the power conversion efficiency (PCE) of
      QDSCs from 5% to nearly 13%, which is comparable to other kinds of emerging solar
      cells. Both the exploration of new QD light-harvesting materials and interface
      engineering have contributed to this fantastically fast improvement. The
      outstanding development trend of QDSCs indicates their great potential as a
      promising candidate for next-generation photovoltaic cells. In this review
      article, we present a comprehensive overview of the development of QDSCs,
      including: (1) the fundamental principles, (2) a history of the brief evolution
      of QDSCs, (3) the key materials in QDSCs, (4) recombination control, and (5)
      stability issues. Finally, some directions that can further promote the
      development of QDSCs in the future are proposed to help readers grasp the
      challenges and opportunities for obtaining high-efficiency QDSCs.

PMID- 30209492
TI  - Solvent engineering for high conversion yields of layered raw materials into
      large-scale freestanding hybrid perovskite nanowires.
AB  - Hybrid organic-inorganic perovskite nanowires have received considerable
      attention for applications in optoelectronic fields; however, practical
      implementation of perovskite nanowires into optoelectronic devices is often
      hindered by low product yields, scaled-up synthesis, or overall lack of synthetic
      control. Herein, we report novel insights into large-scale freestanding lead
      halide perovskite nanowires using a series of solvent effects. A facile pathway
      for converting layered raw materials to nanowires with high conversion yields can
      facilitate the large-scale applications of nanowires, which could help us
      understand the unique aspects of the formation chemistry of the materials. We
      introduced a two-step process to obtain perovskite nanowires without an impurity
      phase that first involves the formation of Pb-containing nanowires with the poor
      solvent drip method. Subsequently, the as-prepared Pb-containing precursors can
      be used as morphology templates for converting completely into perovskite
      nanowires with high conversion yields of 83% through a series of solvent effects,
      such as solvent-driven, solvent-removing, solvent-exchange and solvent-growth.
      The synthetic strategy was demonstrated to be applicable for other perovskite
      based materials, which can offer a comprehensive understanding of the formation
      mechanism of perovskite-based materials.

PMID- 30209493
TI  - The coordination chemistry of phosphinidene sulfides. Synthesis and catalytic
      properties of Pd4 and Pt4 clusters.
AB  - 7-Phosphanorbornene sulfides were used as [RP = S] precursors. The reaction of
      these precursors with [M(PPh3)4] (M = Pd, Pt) yields star-like M4 clusters in
      which the central core is coated by three RP = S units acting as 4-electron MU2
      P, eta2-P = S ligands. The Pd cluster displays both stability and catalytic
      activity in the Suzuki-Miyaura reaction. DFT analysis suggests that a mononuclear
      [eta2-RP = S]Pd(PPh3) complex is involved in the formation of the Pd4 clusters.

PMID- 30209495
TI  - Highly regioselective alpha-alkylation of alpha,beta,gamma,delta-unsaturated
      aldehydes.
AB  - The first alpha-alkylation of alpha,beta,gamma,delta-unsaturated aldehydes is
      achieved under mild reaction conditions. Several alpha,beta,gamma,delta
      unsaturated aldehydes and diarylcarbinols are successfully tested for the
      synthesis of MBH-type alpha-alkylated products with an excellent
      regioselectivity. Simple pyrrolidine is efficiently used as a catalyst to achieve
      a perfect E/Z selectivity of the alpha-alkylated products.

PMID- 30209494
TI  - Discontinuous growth of DNA plectonemes due to atomic scale friction.
AB  - We develop a model to explain discontinuities in the increase of the length of a
      DNA plectoneme when the DNA filament is continuously twisted under tension. We
      account for DNA elasticity, electrostatic interactions and entropic effects due
      to thermal fluctuation. We postulate that a corrugated energy landscape that
      contains energy barriers is the cause of jumps in the length of the plectoneme as
      the number of turns is increased. Thus, our model is similar to the Prandtl
      Tomlinson model of atomic scale friction. The existence of a corrugated energy
      landscape can be justified due to the close proximity of the neighboring pieces
      of DNA in a plectoneme. We assume the corrugated energy landscape to be
      sinusoidal since the plectoneme has a periodic helical structure and rotation of
      the bead is a form of periodic motion. We perform calculations with different
      tensile forces and ionic concentrations, and show that rotation-extension curves
      manifest stair-step shapes under relatively high ionic concentrations and high
      forces. We show that the jump in the plectonemic growth is caused by the
      flattening of the energy barrier in the corrugated landscape.

PMID- 30209496
TI  - Relativistic corrections to the ground states of HD and D2 calculated without
      using the Born-Oppenheimer approximation.
AB  - The Schrodinger equation for the ground states of the hydrogen molecules HD and
      D2 is solved variationally by treating the constituent particles of HD or D2 on
      the same footing without assuming the Born-Oppenheimer approximation. The
      variational basis sets are constructed using Hylleraas coordinates that are
      traditionally adopted for few-electron atomic systems. The nonrelativistic energy
      eigenvalues are converged to the level of 10-6 cm-1. The leading-order
      relativistic corrections, including relativistic recoil terms, are calculated
      rigorously. Together with the higher-order relativistic and quantum
      electrodynamic corrections obtained by the Pachucki's group [Phys. Rev. A., 2017,
      95, 052506; Phys. Rev. Lett., 2018, 120, 153001], we determine the dissociation
      energy of D2 to be 36748.36240(28) cm-1, which agrees with the recent
      experimental result of Liu et al. [J. Chem. Phys., 2010, 132, 154301]
      36748.36286(68) cm-1. For HD, the dissociation energy determined by us is
      36405.78252(27) cm-1, which deviates from the most accurate experimental result
      of Sprecher et al. [J. Chem. Phys., 2010, 133, 111102] 36405.78366(36) cm-1 by
      about 2sigma.

PMID- 30209497
TI  - Mesoporous silica nanoparticles functionalised with a photoactive ruthenium(ii)
      complex: exploring the formulation of a metal-based photodynamic therapy
      photosensitiser.
AB  - A series of nanomaterials based on mesoporous silica have been synthesised and
      functionalised with a photoactive polypyridyl ruthenium(ii) complex, namely
      [Ru(bipy)2-dppz-7-hydroxymethyl][PF6]2 (bipy = 2,2'-bipyridine, dppz =
      dipyrido[3,2-a:2',3'-c]phenazine), by various methods. The functionalisation
      reactions were based on the covalent binding to different ligands attached to the
      pores of the mesoporous nanoparticles and a simple physisorption using polyamino
      functionalised mesoporous silica nanoparticles. The resulting nanostructured
      systems have been characterised by XRD, XRF, BET, SEM and TEM, observing the
      incorporation of the metallodrug onto the nanostructured silica in a different
      way depending on the synthetic method used in the loading reactions. In our
      studies, we have also observed that functionalisation with the metallodrug causes
      changes in the structural and textural features of the materials. The
      phototherapeutic activity of the ruthenium-functionalised materials in HeLa
      cervical cancer cells has been tested and the preliminary results are presented
      herein.

PMID- 30209498
TI  - Correction: Modelling of thermal transport through a nanocellular polymer foam:
      toward the generation of a new superinsulating material.
AB  - Correction for 'Modelling of thermal transport through a nanocellular polymer
      foam: toward the generation of a new superinsulating material' by Guilong Wang et
      al., Nanoscale, 2017, 9, 5996-6009.

PMID- 30209500
TI  - Q-model of electrode reactions: altering force constants of intramolecular
      vibrations.
AB  - A theory of redox reactions involving electron transfer between a metal electrode
      and a molecule in solution is formulated in terms of two types of nuclear
      coordinates of the thermal bath: electrostatic polarization of the medium and
      local low-frequency vibrations. The polarization fluctuations follow Gaussian
      statistics. In contrast, the vibrational coordinate is allowed to change its
      force constant between two oxidation states of the reactant, which is projected
      onto non-Gaussian fluctuations of the reactant's electronic states. A closed-form
      analytical theory for the electrode redox reactions is formulated in terms of
      three reorganization energies: the reorganization energy for the electrostatic
      polarization of the medium and two internal (vibrational) reorganization energies
      for the reduced and oxidized states of the reactant. The theory predicts
      asymmetry between the cathodic and anodic branches of the electrode current
      driven by the corresponding difference in the vibrational force constants.

PMID- 30209499
TI  - A robust core-shell nanostructured nickel-iron alloy@nitrogen-containing carbon
      catalyst for the highly efficient hydrogenation of nitroarenes.
AB  - Currently, the catalytic selective hydrogenation of nitroarenes to produce
      aromatic amines is one of the most important key reactions in many fine chemical
      processes. In particular, non-noble-metal-catalyzed hydrogenation of nitroarenes
      represents more sustainable chemical processes. Here, we report a new robust and
      recyclable core-shell nanostructured nickel-iron alloy@nitrogen-containing carbon
      (NiFe@NC) catalyst and the beneficial effect of alloying Ni with Fe for the above
      reaction. The key to this synthetic strategy was thermally transforming the Ni-Fe
      layered double hydroxide (NiFe-LDH)/melamine mixture to form a fixed NiFe@NC
      nanostructure. A series of characterization results revealed the formation of
      NiFe alloy nanoparticles (NPs) coated with the NC overlayer. The as-fabricated
      NiFe@NC catalyst with a Ni/Fe atomic ratio of 3.0 exhibited superior activity for
      the reduction of the nitro group in o-chloronitrobenzene, with a 99.5% yield of o
      chloroaniline under mild reaction conditions. The initial reaction rate over the
      catalyst was nearly three times that over the monometallic Ni@NC counterpart, and
      even one-order magnitude higher than that over pristine NiFe-LDH-derived NiFe
      alloy NPs. The extraordinary activity of NiFe@NC was reasonably attributed to the
      unique core-shell nanostructure, where both the NiFe alloy core and the NC
      overlayer shell could construct a significant promotional effect, being
      beneficial for the selective cleavage of the N-O bond. Recycling experiments
      indicated that the catalyst could be easily separated and recovered under an
      external magnetic field and experienced excellent recyclability during seventeen
      cycles without an obvious loss of catalytic activity. Furthermore, the present
      catalyst was also highly active for the chemoselective hydrogenation of other
      substituted nitroarenes bearing different functional groups to the corresponding
      anilines.

PMID- 30209501
TI  - Scandium alkyl and hydride complexes supported by a pentadentate diborate ligand:
      reactions with CO2 and N2O.
AB  - Alkyl and hydrido scandium complexes of the dianionic pentadentate ligand B2Pz4Py
      are reported. The key starting material (B2Pz4Py)ScCl is readily prepared and
      alkylated with organolithium reagents RLi (R = CH3, CH2SiMe3, CH2SiMe2Ph,
      CH2CH2CH3 and CH2CHMe2) to form alkyl derivatives in 61-93% yields. These
      compounds are very thermally stable and do not undergo sigma bond metathesis
      reactions with dihydrogen. The hydrido complex was prepared from (B2Pz4Py)ScCl
      and NaHBEt3 in 80% yield and was found to be more stable by 28 kcal mol-1 as a
      dimer, rather than a monomeric hydrido complex. However, the monomer is
      accessible through dissociation of the dimer at 80  degrees C. All of the
      compounds (B2Pz4Py)ScR react with water to form the bridging oxo dimer
      (B2Pz4Py)ScOSc(B2Pz4Py). The reactivity of the hydrido and methyl complexes
      towards carbon dioxide was explored; heating to 80  degrees C results in the
      formation of kappa2 formato and acetate complexes, respectively. The mechanisms
      were studied via density functional theory and distinct transition states for
      insertion of CO2 into the Sc-R (R = H, CH3) were found, with the insertion into
      Sc-CH3 being more enthalpically difficult (by 18 kcal mol-1) than insertion into
      Sc-H. The slow rate of reaction between [(B2Pz4Py)ScH]2 and CO2 is attributed to
      the barrier associated with dimer dissociation. In both insertion reactions, the
      kinetic products are kappa1 formato or acetate complexes that are only slightly
      less stable than the observed kappa2 derivatives. The kappa1 compounds can
      therefore be trapped by treating the kappa2 isomers with tris-pentafluorophenyl
      borane.

PMID- 30209502
TI  - Interplay between structure and relaxation in polyurea networks: the point of
      view from a novel method of cooperativity analysis of dielectric response.
AB  - The influence of structural constraints on the relaxation dynamics of three
      polyurea networks with a varying degree of crosslinking, has been studied by
      means of a thorough analysis of broadband dielectric spectroscopy measurements.
      Two different relaxation processes are observed, namely, a fast process involving
      the soft poly(propylene oxide) chains, and a slower and much broader process
      associated with the immediate surroundings of the hard crosslinkers. Microphase
      separation in soft and hard domains characterizes the systems in the presence of
      hydrogen bonding. In this case, different confinement conditions are explored by
      varying the soft chain length; overall, so called "adsorption" effects dominate.
      With respect to both cooperativity and the rearrangement energy threshold in fast
      relaxation, it is found that the enhancement of configurational constraints is
      similar to cooling, but only on qualitative grounds. An upper bound of the hard
      domains' interface thickness, in which the slow relaxation is believed to take
      place, is estimated from the analysis of the fast relaxation in the system
      characterized by the highest degree of confinement, taking into account the
      results of the structural analysis. Dropping the hydrogen bonding mechanism,
      phase separation does not occur anymore and the configurational constraints at
      the ends of the soft chains are reduced, leaving just those imposed by the rigid
      crosslinkers. This leads to a significant increase in cooperativity on
      approaching the glass transition, and to a complex behavior that is thoroughly
      discussed in comparison with those observed in the micro-segregated systems.

PMID- 30209503
TI  - Cobalt-catalyzed cyclization of benzamides with alkynes: a facile route to
      isoquinolones with hydrogen evolution.
AB  - The reaction of benzamides with alkynes assisted by an 8-aminoquinoline ligand in
      the presence of Co(OAc)2.4H2O and pivalic acid under an air atmosphere provided
      isoquinolone derivatives in good to excellent yields. In this reaction, the
      active Co(iii) species is regenerated by the reaction of Co(i) species with
      pivalic acid under an air atmosphere with hydrogen evolution. The proposed
      mechanism was supported by competition experiments, deuterium labelling studies,
      radical scavenger experiments and kinetic studies.

PMID- 30209504
TI  - Origin of green photoluminescence in four-ring bent-core molecules with ESIPT,
      selective sensing of zinc ions by turn-on emission and their liquid crystal
      properties.
AB  - Fluorescent four-ring symmetrical/unsymmetrical molecules containing alkyl chains
      of a varied number of -CH2- groups with a bent-core have been synthesized to
      explore their liquid crystalline (LC) and photophysical properties. Some of these
      molecules depending upon their alkyl chain length were found to exhibit B1 and B7
      liquid crystalline phases and are characterized by various analytical techniques
      such as FT-IR, 1H NMR, mass, POM, DSC, single crystal XRD, etc. Crystal structure
      determination reveals the hydrogen bonded enol form of these molecules with non
      planar bent-molecular geometry. Intramolecular hydrogen bonding was found to play
      an important role in the stabilization of these molecules and in the origin of
      their green photoluminescence (GPL). The photo-physical experimental results
      through various control experiments clearly demonstrate that the origin of the
      large Stokes shifted GPL of these molecules can be attributed to the excited
      state intramolecular proton transfer (ESIPT) process. The formation of various
      types of anionic species and their stability were explored through steady-state
      and time-resolved fluorescence measurements. These compounds are found to be good
      turn-on PL probes in the selective detection of zinc ions at the micromolar
      level. Upon binding of zinc ions with the bent-core molecule, the structural
      changes have been investigated through NMR spectroscopy.

PMID- 30209505
TI  - Optically induced motion of liquid crystalline droplets.
AB  - The controlled motion of a liquid crystalline active droplet was demonstrated in
      a surfactant solution and by irradiation with UV light. The droplet could be
      induced to roll on a glass substrate toward the UV light source. This was
      explained by the Marangoni flow induced by the UV-induced desorption of
      surfactants.

PMID- 30209506
TI  - The [4 + 2] cyclization/retro-Mannich reaction cascade of para-quinone methide
      derivatives with Pd-containing 1,4-dipoles.
AB  - The first [4 + 2] cyclization/retro-Mannich reaction cascade of para-quinone
      methides with Pd-containing 1,4-dipoles generated in situ from vinyl
      benzoxazinanones has been established. The corresponding rearrangement products
      were obtained in generally good to excellent yields (up to 92% yield). This
      reaction represents the first example of C[double bond, length as m-dash]C double
      bond cleavage of para-quinone methides, which will greatly enrich the chemistry
      of quinone methides.

PMID- 30209507
TI  - A family of mixed-lanthanide metal-organic framework thermometers in a wide
      temperature range.
AB  - By choosing 2-pyridin-4-yl-4,5-imidazoledicarboxylic acid (H3PIDC) as the first
      ligand and sodium oxalate (OX) as the ancillary ligand, a series of mixed
      lanthanide metal-organic frameworks (M'LnMOFs) [Tb1-xEux(HPIDC)(ox)1/2H2O].3H2O
      (x = 0 1, 0.01 2a, 0.03 2b, 0.05 2c, 0.08 2d, 0.1 2e, 0.3 2f, 0.5 2g, 1 3) have
      been successfully synthesized via hydrothermal reactions. 2a-2f can serve as
      ratiometric luminescent sensors for detecting temperature. In this co-doped
      system, 2d shows an excellent linear response relationship with temperature from
      303 to 473 K and exhibits a maximum relative sensitivity (Sr) of 0.60% K-1 at 473
      K. Furthermore, powder X-ray diffraction (PXRD) experiments indicate that 2d has
      excellent chemical stability under simulated physiological conditions and alkali
      acid solutions with pH ranging from 4 to 11, which makes it suitable to be
      applied in the physiological environment.

PMID- 30209508
TI  - Thermoelectric properties of two-dimensional selenene and tellurene from group-VI
      elements.
AB  - Single-layered two-dimensional (2D) materials have become very attractive due to
      their novel electronic behavior after the discovery of graphene. Here, we report
      the electronic structure and thermoelectric properties of single-layered 2D
      selerium (selenene) and tellurium (tellurene) by using density functional theory
      calculation. Both selenene and tellurene show three-phonon limited thermal
      conductivity. The prominent anharmonic phonon scattering process for tellurene
      makes it show the lowest lattice thermal conductivity among 2D single elemental
      materials till now. Their special square unit cells give rise to a highly
      anisotropic electronic structure along the zigzag and the armchair direction. The
      large effective mass and Seebeck coefficient along the armchair direction suggest
      that the thermal performance is better than that of the zigzag direction. The
      effect of spin-orbit coupling increases the band gap and is found to be crucial
      for tellurene. These studies provide a way to tune the thermoelectric properties
      of selenene and tellurene in the future.

PMID- 30209509
TI  - Mechanics and nanovoid nucleation dynamics: effects of polar functionality in
      glassy polymer networks.
AB  - We use molecular simulations and experiments to rationalize the properties of a
      class of networks based on dicyclopentadiene (DCPD), a polymer with excellent
      fracture toughness and a high glass transition temperature (Tg), copolymerized
      with 5-norbornene-2-methanol (NBOH). DCPD is a highly non-polar hydrocarbon,
      while NBOH contains a hydroxy group, introducing polar functionality and hydrogen
      bonds (H-bonds). NBOH thus represents a possible route to improve the chemical
      compatibility of DCPD-based networks with less-hydrophobic materials. We
      systematically vary the NBOH content (polar chemistry) in DCPD networks, while
      keeping other network parameters nearly constant, including the molecular weight
      between cross-links, chain rigidity, and Tg. Using molecular dynamics (MD)
      simulations, we quantify the thermovolumetric and mechanical properties,
      including Tg, cohesive energy density, stiffness, and yield strength. We compare
      these results with experiments on networks of similar composition, finding good
      agreement. The relation between these properties and polar chemistry are studied
      by examining a secondary network of physical cross-links, formed by hydrogen
      bonds between NBOH units. Further, we examine nanovoid formation, an energy
      dissipation mechanism hypothesized to contribute to the toughness of pDCPD. Using
      metadynamics to accelerate sampling, we quantify the nanovoid nucleation rate
      under hydrostatic tension, similar to the stress state in the plastic zone
      preceding a crack tip. Small additions of NBOH have minimal effect, but the rate
      drops steeply with larger amounts. Several properties are mapped at nanometer
      scales, including stiffness and mobility, and associated with void nucleation.
      Estimates of the length- and time-scale of the plastic zone near a crack tip are
      used in discussing nanovoid formation as a plausible toughening mechanism in
      these materials. Overall, the results suggest that pDCPD tolerates the addition
      of some polar chemistry without degrading its excellent mechanical properties.

PMID- 30209510
TI  - Rhodium-catalyzed cyclization of acceptor-substituted biphenyl alpha
      diazoketones: a study of the substitution effect on chemoselectivity.
AB  - A range of biphenyl alpha-diazoketones containing various electron-withdrawing
      groups (EWG = COCH3, CN, CO2Et, COPh, SO2CH3, SO2Ph) on diazo carbon has been
      investigated for rhodium(ii)-catalyzed intramolecular cyclization. Among which,
      the alpha-acetyl, carboxylate and cyano substituted substrates show markedly
      different selectivity between aromatic substitution and aromatic cycloaddition
      processes, affording phenanthrol and/or benz[alpha]azulenone products in varying
      ratios. The selectivity is mainly directed by alpha-substitutions, and is also
      possibly influenced by the substituents on the biphenyl ring. Moreover, high
      chemoselectivity for aromatic substitution over cycloaddition is observed for the
      alpha-benzoyl and sulfonyl substituted substrates. But in addition to
      phenanthrols, these reactions produce aromatic ketones and/or 1,2-diketones as
      unprecedented products obtained from diazo precursors. Mechanistic rationales are
      given in the report.

PMID- 30209511
TI  - [Psychological factors following ankle fractures : A review article].
AB  - Ankle fractures have many short and long-term consequences for patients. For this
      reason, psychosocial factors also play a role in the success of the treatment in
      addition to the surgical treatment. The aim of this article is to give an
      overview of the psychological aspects in the context of fractures as well as
      explanatory models for the different ways of coping. In addition, an overview of
      the empirical data with respect to psychological influences and outcome factors
      in lower extremity fractures, specifically ankle fractures, is given. The current
      research indicates that psychosocial factors have a decisive influence on the
      physical and psychological outcome.

PMID- 30209512
TI  - Binding properties of broad-specific monoclonal antibodies against three
      organophosphorus pesticides by a direct surface plasmon resonance immunosensor.
AB  - In this study, heterologous indirect competitive enzyme-linked immunosorbent
      assay (icELISA) was introduced into the screening of hybridomas for the
      development of broad-specific monoclonal antibodies (mAbs) against
      organophosphorus (OP) pesticides. After immunization, two formats of icELISA
      based on the homologous hapten antigen and four heterologous hapten antigens were
      conducted for hybridoma screening. Two mAbs 2G6 and 7B2 with good recognition
      toward three OP pesticides (parathion, methyl-parathion, and fenitrothion) were
      produced. Results of the icELISA showed that the two mAbs exhibited high
      sensitivity against three OP pesticides, with IC50 ranging from 2.93 to 19.71 ng
      mL-1. Moreover, a non-competitive surface plasmon resonance (SPR) immunosensor
      was used for characterizing the binding properties of the mAbs to OP pesticides.
      After kinetic analysis, equilibrium dissociation constant (KD) values of mAbs 2G6
      and 7B2 were calculated as 1.45 * 10-9 M and 4.26 * 10-9 M for parathion, 6.75 *
      10-9 M and 4.17 * 10-9 M for methyl-parathion, and 2.44 * 10-8 M and 1.19 * 10-8
      M for fenitrothion, respectively. Whereas, both icELISA and SPR-based immunoassay
      indicated that the two mAbs could not recognize other five OP analogs. Since SPR
      based immunoassay provides comprehensive information of two molecules directly
      interacting with each other, it is a valuable tool during the development and
      characterization of broad-specific mAbs. Graphical abstract ?.

PMID- 30209515
TI  - [Fulminant acute kidney injury after cholecystectomy in a 45-year-old female
      patient].
AB  - A cholecystectomy was carried out on a 45-year-old female patient with fever,
      myalgia and right upper abdominal pain because of a suspected cholecystitis.
      Postoperatively acute kidney injury occurred. A comprehensive medical history
      taken later revealed a presumed occupational contact to rodents. Serological
      testing detected a recent infection with Dobrava-Belgrade hantavirus. The kidney
      function normalized with supportive therapeutic measures. Hantavirus infection
      should be considered in the differential diagnosis of acute kidney injury
      combined with fever, myalgia and abdominal pain.

PMID- 30209514
TI  - [Cardiac contractility modulation].
AB  - Cardiac contractility modulation (CCM) is a device-based electrical therapy for
      the additive treatment of chronic drug-refractory heart insufficiency. High
      amplitude signals are applied during the absolute refractory period and have been
      shown to enhance the strength of left ventricular (LV) contraction and improve
      exercise tolerance and quality of life. The mechanisms of action appear to
      involve effects on myocardial gene expression and on normalization of key
      myocardial proteins. So far, more than 3500 CCM devices have been implanted
      worldwide. For patients with therapy refractory heart insufficiency and narrow
      QRS complex, CCM is together with baroreceptor activation the only additive
      electrical therapy which had been approved in Germany. For the first time CCM has
      been referenced in the current guidelines on cardiac insufficiency. Prognostic
      data with respect to mortality have been evaluated in case series. Ongoing
      randomized trials and registries will address these specific endpoints and have
      to a significant extent already been recently published. A Food and Drug
      Administration (FDA) approval is expected within the next few months.

PMID- 30209513
TI  - [Non-beneficial therapy and emotional exhaustion in end-of-life care : Results of
      a survey among intensive care unit personnel].
AB  - BACKGROUND: End-of-life care (EOLC) in the intensive care unit (ICU) is becoming
      increasingly more common but ethical standards are compromised by growing
      economic pressure. It was previously found that perception of non-beneficial
      treatment (NBT) was independently associated with the core burnout dimension of
      emotional exhaustion. It is unknown whether factors of the work environment also
      play a role in the context of EOLC. OBJECTIVE: Is the working environment
      associated with perception of NBT or clinician burnout? MATERIAL AND METHODS:
      Physicians and nursing personnel from 11 German ICUs who took part in an
      international, longitudinal prospective observational study on EOLC in 2015-2016
      were surveyed using validated instruments. Risk factors were obtained by
      multivariate multilevel analysis. RESULTS: The participation rate was 49.8% of
      personnel working in the ICU at the time of the survey. Overall, 325 nursing
      personnel, 91 residents and 26 consulting physicians participated. Nurses
      perceived NBT more frequently than physicians. Predictors for the perception of
      NBT were profession, collaboration in the EOLC context, excessively high workload
      (each p <= 0.001) and the numbers of weekend working days per month (p = 0.012).
      Protective factors against burnout included intensive care specialization (p =
      0.001) and emotional support within the team (p <= 0.001), while emotional
      exhaustion through contact with relatives at the end of life and a high workload
      were both increased (each p <= 0.001). DISCUSSION: Using the example of EOLC,
      deficits in the work environment and stress factors were uncovered. Factors of
      the work environment are associated with perceived NBT. To reduce NBT and
      burnout, the quality of the work environment should be improved and intensive
      care specialization and emotional support within the team enhanced.
      Interprofessional decision-making among the ICU team and interprofessional
      collaboration should be improved by regular joint rounds and interprofessional
      case discussions. Mitigating stressful factors such as communication with
      relatives and high workload require allocation of respective resources.

PMID- 30209516
TI  - Inhibition of vection by grasping an object.
AB  - The present study investigated whether vection could be modified by an object
      grasping movement. Twenty-five university students were asked to do one of the
      following four types of left-hand movements while they were viewing a radial
      optic flow: (1) grasping the hand-gripper strongly; (2) holding the hand-gripper;
      (3) clenching fist strongly; and (4) open hand without having anything in their
      left hands (normal hand condition). The participants' tasks were to keep pressing
      a button with their right hands while they were perceiving vection. After each
      trial, they estimated the subjective strength of vection on a 101-point scale.
      The result showed that the vection was inhibited by strongly grasping the hand
      gripper task more than by the other hand movements. Vection could be weakened by
      the object grasping movement. It might be suggested that vection could be
      inhibited by the presence of an object being grasped and also by the grasping
      movement itself. We speculated that the mechanism underlying this inhibition
      might be related to cognitive pressure, attentional load, power and muscle tonus,
      and multisensory and proprioception interactions.

PMID- 30209519
TI  - Anticoagulant plus antiplatelet therapy for atrial fibrillation : Cost-utility of
      combination therapy with non-vitamin K oral anticoagulants vs. warfarin.
AB  - BACKGROUND: Emerging evidence indicates combination therapy with anticoagulants
      and antiplatelet agents for atrial fibrillation (AF) will be increasingly
      required. Numerous studies compare the efficacy and cost-effectiveness of
      anticoagulation alone in AF, i. e., non-vitamin K oral anticoagulants (NOACs) vs.
      warfarin. However, the addition of antiplatelet agents with their potential for
      decreasing thromboembolic stroke counter-balanced by an increased bleeding risk
      has received less attention. Thus, we evaluated the cost-utility of this
      combination therapy. METHOD AND RESULTS: We obtained event estimates from our
      recent meta-analysis of four randomized clinical trials designed to compare NOACs
      with warfarin in patients with AF. We examined patient subgroups within each
      trial that received antiplatelet therapy in addition to anticoagulation.
      Utilities were derived from the literature and cost estimates from the German
      health-care system. A decision tree was constructed and populated with these
      parameters. We used a 1-year time horizon because combination therapy is not
      recommended beyond this time. We calculated the incremental cost-effectiveness
      ratio (ICER) per quality-adjusted life-year (QALY). The derived ICER was
      13,168.50 ? per QALY. NOAC prices exerted considerable influence on the
      calculation. Nevertheless, there is potential for ICER shifts in favor of
      warfarin, e.g., if warfarin-mediated anticoagulation control is improved and
      thereby adverse events decrease. Conversely, if NOAC adherence decreases, adverse
      events could increase. CONCLUSION: The derived ICER was 13,168.50 ? per QALY,
      consistent with NOACs being cost-effective vs. warfarin when anticoagulation is
      used with antiplatelet agents. Nevertheless, country-, practice-, and patient
      related factors influence the ICER. Our cost-utility calculation should be used a
      starting point for decision-making.

PMID- 30209518
TI  - [Multipoint pacing-more CRT or a waste of battery power?]
AB  - Cardiac resynchronization therapy (CRT) reduces morbidity and mortality in
      patients with broad QRS complex >=130 ms and heart failure with reduced ejection
      fraction despite optimal guideline-directed medical therapy. However,
      approximately 30% of the patients implanted with a CRT system do not show
      clinical benefit. Reasons for nonresponse are complex and some aspects can be
      addressed during follow-up. Based on quadripolar lead technology, multipoint
      pacing (MPP) allows left ventricular stimulation at two different sites along the
      lead. In particular, in scarred and fibrotic ventricular myocardium stimulation
      at two different sites may overcome conduction barriers and lead to homogeneous
      ventricular depolarization. Especially for patients that do not respond to
      conventional CRT, activation of MPP may present an option to increase clinical
      response. On the other hand, MPP may significantly decrease battery
      longevity.This review offers an overview of the current knowledge and data on MPP
      balancing the potential clinical benefit and the possible disadvantages of this
      therapy.

PMID- 30209517
TI  - The neural correlates of flow experience explored with transcranial direct
      current stimulation.
AB  - The experience of flow ensues when humans engage in a demanding task while task
      demands are balanced with the individual's level of skill or ability. Here, we
      further tested the hypothesis that the medial prefrontal cortex (MPFC) plays a
      causal role in mediating flow experience using transcranial direct current
      stimulation (tDCS) to interfere with MPFC's deactivation evoked by a flow
      paradigm and measured by magnetic resonance (MR)-based perfusion imaging. In a
      balanced, within-subjects repeated measure design, three treatments of tDCS
      (sham, anodal, cathodal) were applied in a sample of 22 healthy male
      participants. tDCS-modulatory effects on flow-specific regional cerebral blood
      flow (rCBF) and subjective flow experience significantly depended on
      participants' baseline level of flow experience during sham tDCS. Those
      participants with lower-flow experience during sham tDCS (LF) benefitted from
      tDCS, particularly from the anodal polarity, whereas both active treatments did
      not substantially affect subjects with relatively higher baseline flow experience
      (HF). Functionally, in LF subjects, relative deactivation of the right amygdala
      got more pronounced under anodal and cathodal tDCS, and changed inconsistently in
      HF subjects. Inter-individual regression analyses of rCBF data suggested that
      involvement of the subgenual anterior cingulate cortex appears crucial for
      affecting the response pattern in the right amygdala and can be modulated by
      tDCS. Present data support the notion that valuable insights into the neural
      mechanism of flow can be obtained using tDCS. However, a clearer understanding of
      tDCS' baseline dependency in terms of individual variations in brain connectivity
      states appears a necessary prerequisite to exploit this technique further.

PMID- 30209520
TI  - Anterior cruciate ligament reconstruction with an all-epiphyseal "over-the-top"
      technique is safe and shows low rate of failure in skeletally immature athletes.
AB  - PURPOSE: The aim of this study was to follow up, clinically and radiographically,
      skeletally immature patients who underwent ACL reconstruction with an all
      epiphyseal "over-the-top" technique. METHODS: Twenty athletes aged between 8 and
      13 years were enrolled and retrospectively evaluated. The subjects underwent
      surgical ACL reconstruction between 2009 and 2013. The surgical technique
      consisted of a single-bundle all-epiphyseal ACL reconstruction with an extra
      articular lateral tenodesis. The mean follow-up was 54 months [34-123] after
      surgery. Clinically, the patients were evaluated pre- and post-operatively with
      Lysholm and KOOS scores; sport activity level was evaluated using the pre-injury,
      pre-operative and post-operative Tegner scores. Objective IKDC was calculated
      post-operatively. The joint laxity was evaluated by KT1000 and Rolimeter
      arthrometers. Panoramic AP standing radiographs of the lower limbs and lateral
      knee radiographs were also taken at the follow-up to evaluate limb length
      discrepancies (LLD) and axial malalignment. Normally distributed parameters were
      presented as mean +/- standard deviation, while the non-normally distributed
      parameters were presented as median [25 degrees  percentile, 75 degrees 
      percentile]. RESULTS: Clinical scores showed significant (P < 0.01) improvement:
      Lysholm and KOOS scores improved from 40 [22; 65] and 59 [42, 73], respectively,
      to 100 [95; 100] and 99 [97;100] after surgery. Tegner score improved from 2 [2;
      2] pre-operatively to 7 [3; 9] at follow-up (P < 0.01). At follow-up, IKDC score
      was A for 19 patients and one who scored B. All patients returned to sport
      activity and had good stability at follow-up: the KT1000 showed a median side-to
      side difference of 0.0 mm [- 0.4; 1.0] for the standard force evaluation and 0.0
      mm [- 1.0; 0.8] for manual-maximum test. The Rolimeter showed median side-to-site
      difference of 0.0 mm [- 1.0; 0.8]. Three minor leg length discrepancies and axial
      deviations were observed at the radiograph: one patient had 0.6 cm lengthening
      and 4 degrees  of varus, one had 1 cm lengthening, and one had 3 degrees  of
      varus (in comparison with the non-operated limb). No re-injury was observed.
      CONCLUSION: This study demonstrates that the modified all-epiphyseal single
      bundle "over-the-top" technique is a viable and safe option for ACL
      reconstruction in pediatric subjects. These results support once more that not
      only ACL reconstruction is a safe procedure in skeletally immature patients, but
      also it is highly recommended for those who want to pursue an active and sportive
      life. LEVEL OF EVIDENCE: Case series, IV.

PMID- 30209522
TI  - Transarterial radioembolization in patients with hepatocellular carcinoma of
      intermediate B2 substage.
AB  - PURPOSE: Patients with hepatocellular carcinoma (HCC) of intermediate stage (BCLC
      B according to the Barcelona Clinic Liver Cancer classification) are a
      heterogeneous group with different degrees of liver function impairment and
      tumour burden. The recommended treatment is transarterial chemoembolization
      (TACE). However, patients in this group may be judged as poor candidates for TACE
      because the risk-benefit ratio is low. Such patients may receive transarterial
      radioembolization (TARE) only by entering a clinical trial. Experts have proposed
      that the stage could be further divided into four substages based on available
      evidence of treatment benefit. We report here, for the first time, the outcome in
      patients with BCLC-B2 substage HCC treated with TARE. METHODS: A retrospective
      analysis of the survival of 126 patients with BCLC-B2 substage HCC treated with
      TARE in three European hospitals was performed. RESULTS: Overall median survival
      in patients with BCLC-B2 substage was not significantly different in relation to
      tumour characteristics; 19.35 months (95% CI 8.27-30.42 months) in patients with
      a single large (>7 cm) HCC, and 18.43 months (95% CI 15.08-21.77 months) in
      patients with multinodular HCC (p = 0.27). However, there was a higher proportion
      of long-term survivors at 36 months among those with a single large tumour (29%)
      than among those with multiple tumours (16.8%). CONCLUSION: Given the poor
      efficacy of TACE in treating patients with BCLC-B2 substage HCC, TARE treatment
      could be a better choice, especially in those with a large tumour.

PMID- 30209521
TI  - [Surgical treatment of bites].
AB  - OBJECTIVE: Thorough and profound debridement for acute bite injuries while
      sparing nerves, vessels and tendons. INDICATIONS: Acute traumatic and late
      presented bite injuries. CONTRAINDICATIONS: General contraindication for
      anesthesia or surgery. SURGICAL TECHNIQUE: Extensive flabellate local
      anesthesia/general anesthesia, wound irrigation using 0.9% NaCl or antiseptic
      solutions, removal of avital tissues, wound debridement, wound edge excision,
      anew extensive irrigation, drainage if necessary, wound closure where applicable
      (except older or punctual deep injuries), bandage, elastic wrapping and
      immobilization. If necessary, plastic surgery with coverage of remaining defects.
      POSTOPERATIVE MANAGEMENT: Immobilization with initially daily wound evaluation,
      removal of drainage/loop on postoperative day 2; if necessary, antibiotic therapy
      with amoxicillin and clavulanic acid in high-risk wounds (e.g., puncture wounds,
      joint or bone involvement, extensive soft tissue squeezing), suture removal on
      day 10-12 after surgery. RESULTS: Of 142 bite injuries that were treated and
      retrospectively evaluated, 46% were caused by dogs and 32% by cats. Patients were
      on average 44 years old; 55% of all dog bites affected women, but 67% of all cat
      bites. In 48% of the cases, general anesthesia was necessary. The postoperative
      infection rate was 6.3%.

PMID- 30209524
TI  - Normal Values for Left Ventricular Mass in Relation to Lean Body Mass in Child
      and Adolescent Athletes.
AB  - It has been demonstrated that regular sport activity in children leads to
      physiological changes in the heart including increased left ventricular (LV)
      myocardial thickness and mass (LVM). The aim of the study was to establish the
      first specific normal values of LVM for child and adolescent athletes.
      Parasternal long-axis, 2D-guided echocardiographic measurements were obtained
      from a group of 791 Caucasian child athletes (age 5-18 years, 58.7% boys). For
      the preparation of normative data, LVM-for-lean body mass (LBM) reference curves
      were constructed using the LMS method. Then, a simple correlation plot was
      constructed to analyse the concordant and discordant indications of left
      ventricular hypertrophy (LVH), defined as LVM-for-LBM above the 95th percentile,
      according to the newly created and previously published normative data on LVM-for
      LBM in the general population of children. Reference scatter plots of LVM-for-LBM
      for boys and girls in the analysed group of children practicing sports were
      presented, showing mean values of LVM and z-scores. The application to the
      studied group of reference centiles established for the general population of
      children would lead to false positive misclassification of increased LVH in 5.8%
      of the girls and 17.0% of the boys. We present the first specific normative data
      for LV mass in relation to lean body mass in Caucasian children and adolescents
      engaged in regular sport activities. The application of specific normative data
      for LV mass results in fewer false positive findings of left ventricular
      hypertrophy in this group than that of reference values for general paediatric
      population.

PMID- 30209523
TI  - The association between diabetes status, HbA1c, diabetes duration, microvascular
      disease, and bone quality of the distal radius and tibia as measured with high
      resolution peripheral quantitative computed tomography-The Maastricht Study.
AB  - : In this small cross-sectional study of predominantly well-treated participants
      with relatively short-term type 2 diabetes duration, HbA1c > 7% (53 mmol/mol) was
      associated with lower cortical density and thickness and higher cortical porosity
      at the distal radius, lower trabecular thickness at the distal tibia, and higher
      trabecular number at both sites. INTRODUCTION: To examine the association between
      diabetes status and volumetric bone mineral density (vBMD), bone
      microarchitecture and strength of the distal radius and tibia as assessed with HR
      pQCT. Additionally-in participants with type 2 diabetes (T2DM), to examine the
      association between HbA1c, diabetes duration, and microvascular disease (MVD) and
      bone parameters. METHODS: Cross-sectional data from 410 (radius) and 198 (tibia)
      participants of The Maastricht Study (mean age 58 year, 51% female). Diabetes
      status (normal glucose metabolism, prediabetes, or T2DM) was based on an oral
      glucose tolerance test and medication history. RESULTS: After full adjustment,
      prediabetes and T2DM were not associated with vBMD, bone microarchitecture, and
      strength of the radius and tibia, except for lower trabecular number (Tb.N) of
      the tibia (- 4%) in prediabetes and smaller cross-sectional area of the tibia (-
      7%) in T2DM. In T2DM, HbA1c > 7% was associated with lower cortical vBMD (- 5%),
      cortical thickness (- 16%), higher cortical porosity (+ 20%) and Tb.N (+ 9%) of
      the radius, and higher Tb.N (+ 9%) and lower trabecular thickness (- 13%) of the
      tibia. Diabetes duration > 5 years was associated with higher Tb.N (+ 6%) of the
      radius. The presence of MVD was not associated with any bone parameters.
      CONCLUSIONS: In this study with predominantly well-treated T2DM participants with
      relatively short-term diabetes duration, inadequate blood glucose control was
      negatively associated with cortical bone measures of the radius. In contrast,
      trabecular number was increased at both sites. Studies of larger sample size are
      warranted for more detailed investigations of bone density and bone quality in
      patients with T2DM.

PMID- 30209525
TI  - Digital templating without a calibration marker is accurate at predicting implant
      size for hip hemiarthroplasty.
AB  - INTRODUCTION: This study aims to assess the accuracy of digital templating for
      hip hemiarthroplasty using radiographs without calibration. METHODS: Two
      independent, blinded observers retrospectively utilised digital software to
      template 50 consecutive patients who had hip hemiarthroplasty. The templated
      parameters (head size, offset and stem size) derived from pre-operative
      radiographs were compared to the actual prosthetic sizes used intra-operatively.
      Inter and intra-observer variabilities were calculated. RESULTS: Both observers
      correctly templated the offset and head size (+/- 2 mm) used in 90% (n = 45) of
      cases. The femoral stem size (+/- 1 size) was correctly predicted by templating
      in over 84% of the cases (n = 42). Inter-observer agreement was excellent for
      femoral head size with an intra-class correlation coefficients (ICC) of 0.94,
      substantial for offset (k = 0.7) but only fair for stem size (k = 0.27). ICC
      values comparing the actual prostheses inserted with the template values were
      excellent for head size (ICC = 0.96), substantial to near perfect for offset (k =
      0.78, 0.85) and fair to moderate (k = 0.24, 0.45) for stem size. CONCLUSION:
      Digital templating of radiographs without calibration can be used to accurately
      and reliably predict femoral head size and offset at a set magnification of 120%.
      Femoral stem size, however, is more difficult to template adequately on pre
      operative radiographs without calibration.

PMID- 30209526
TI  - Translational research: what is the value of experimental studies in comparison
      with clinical studies to help understand clinical problems?

PMID- 30209527
TI  - Circulating Levels of Inflammation and the Effect on Exercise-Related Changes in
      Bone Mass, Structure and Strength in Middle-Aged and Older Men.
AB  - Chronic, low-grade systematic inflammation has been associated with bone loss and
      increased fracture risk. We previously reported that exercise improved femoral
      neck bone mineral density (BMD), geometry and strength and lumbar spine
      trabecular BMD in middle-aged and older men, but had no effect on markers of
      inflammation. The aim of this study was to examine the association between basal
      inflammatory status and the adaptive skeletal responses to exercise. Secondary
      analysis was completed on 91 men aged 50-79 years who participated in an 18-month
      program of progressive resistance training plus weight-bearing impact exercise (3
      day/week) with and without additional calcium-vitamin D3. Markers of inflammation
      (serum hs-CRP, TNF-alpha and IL-6) and DXA and QCT-derived BMD, bone structure
      and strength at the lumbar spine and proximal femur were measured at baseline and
      18 months. Multiple regression was used to assess associations between skeletal
      changes and both baseline levels of individual inflammatory markers and a
      composite inflammatory index derived from the number of markers categorized into
      the highest tertile. Baseline serum hs-CRP, TNFalpha and IL-6 and the composite
      inflammatory index score were not associated with skeletal changes at any site
      after adjusting for age, change in lean mass, disease(s)/medication use and
      adherence to the exercise intervention. In conclusion, this study indicates that
      basal inflammatory status does not influence the osteogenic response to exercise
      training in healthy middle-aged and older men.

PMID- 30209528
TI  - Vitamin D and Bone Mineral Density in HIV Newly Diagnosed Therapy-Naive Patients
      Without Any Secondary Causes of Osteoporosis.
AB  - Bone loss and vitamin D deficiency are common in HIV patients. However, bone
      health status in newly diagnosed HIV patients has not been thoroughly described.
      Our aim was to assess the bone mineral density (BMD), bone resorption and vitamin
      D status in newly diagnosed HIV patients. A prospective observational study in
      HIV newly diagnosed therapy-naive persons. Patients with secondary causes of
      osteoporosis were excluded. Bone densitometry (DXA), a bone resorption marker
      (CTx), 25-hydroxyvitamin D (25OHD), CD4 count and HIV viral load (VL) were done
      in 70 patients. Vitamin D results were compared with a group of healthy
      volunteers. All patients were men, mean age 31 years (19-50). Low BMD (Z score <=
      2.0) was found in 13%, all of them in lumbar spine, and in only one patient also
      in femoral neck. Bone resorption was high in 16%. One out of four participants
      had low BMD or high bone resorption. Vitamin D deficiency (25OHD < 20 ng/mL) was
      found in 66%. Mean 25OHD in patients was significantly lower than in healthy
      volunteers (p = 0.04). No associations were found between BMD, CTx, 25OHD and VL
      or CD4 count. We hypothesize that HIV infection negatively affects bone health
      based on the results we found among newly diagnosed, therapy-naive, HIV-infected
      patients, without any known secondary causes of osteoporosis. Low BMD or high
      bone resorption, are significantly prevalent in these patients. HIV-infected
      patients had a higher prevalence of vitamin D deficiency than controls, which was
      not correlated with CD4 count or VL.

PMID- 30209529
TI  - ?

PMID- 30209530
TI  - ?

PMID- 30209531
TI  - ?

PMID- 30209533
TI  - The role of stress-reactivity, stress-recovery and risky decision-making in
      psychosocial stress-induced alcohol consumption in social drinkers.
AB  - RATIONALE: Chronic alcohol misuse can escalate into alcohol use disorder (AUD).
      The causal mechanisms through which recreational social drinking develops into
      compulsive uncontrolled alcohol misuse are multifaceted. For example, stress is
      an important risk factor that influences alcohol craving in both healthy and
      addicted individuals. In addition, those that are high in impulsivity/risk taking
      drink more and are at greater risk of developing addiction. At present, however,
      it is not possible accurately to predict those at risk of escalation in alcohol
      use, or of developing AUD. OBJECTIVES: The aim of this study was to investigate
      how underlying physiological and personality traits affect stress-induced craving
      for, and consumption of, alcohol, in a sample of social drinkers. The primary
      hypothesis was that impulsivity/risk-taking would modulate stress-induced alcohol
      craving and consumption. METHODS: Thirty-nine participants (22 male and 17
      female; mean age = 23.92 years [SD = 4.90]) were randomly allocated to 'stress'
      and 'no-stress' groups; in the stress group, participants took part in the Trier
      Social Stress Test (TSST). Participants completed several questionnaires and
      computer tasks in order to assess prior alcohol use, impulsivity/risk-taking,
      stress-reactivity, craving and physiological biomarkers of stress. Finally,
      participants completed a voluntary drinking task, in which increasing numbers of
      presses on a computer keyboard were reinforced with 5-ml shots of 37% ABV vodka
      (plus mixer). RESULTS: Participants exposed to the TSST showed an increase in
      craving following the stressor. Several factors predicted voluntary drinking,
      including risky decision making, slow HR recovery from stress, poor vagal tone
      during recovery from stress and greater stress reactivity. Surprisingly, we found
      no correlation between craving and consumption. CONCLUSIONS: Our data suggest
      that variation in physiological stress parameters and poor decision-making
      abilities increase risk of stress-induced alcohol consumption. This may provide a
      useful translational framework through which we can further study early
      predictive markers for the shift between controlled recreational drinking to
      uncontrolled alcohol misuse, including AUD.

PMID- 30209532
TI  - Comparison of the effects of abstinence on MDMA and cocaine self-administration
      in rats.
AB  - RATIONALE: 3,4-Methylenedioxymethamphetamine (MDMA) preferentially increases
      synaptic serotonin (5HT). This response was attenuated following repeated
      exposure but there was recovery as a result of abstinence. Effects of abstinence
      on self-administration of many drugs have been documented but the impact on MDMA
      self-administration is unknown. OBJECTIVE: This study compared the effects of
      abstinence on MDMA and cocaine self-administration. METHODS: Six-hour daily MDMA
      or cocaine sessions were conducted until a total of 350 mg/kg had been self
      administered. Following this, rats were randomly assigned to either a 0- or 14
      day abstinence group. Self-administration testing then continued for an
      additional 7 days. RESULTS: The latency to self-administer 350 mg/kg was shorter
      for rats that self-administered cocaine. The temporal distribution of responding
      within each test session also differed; MDMA self-administration was high during
      the first hour of each session, and decreased during subsequent hours, whereas
      cocaine self-administration was evenly distributed throughout each hour of the
      session. Abstinence decreased MDMA but not cocaine self-administration.
      CONCLUSIONS: The selective reduction of MDMA self-administration following
      abstinence is consistent with the idea that MDMA-stimulated 5-HT release is
      inhibitory to MDMA self-administration.

PMID- 30209535
TI  - MRI-guided localization of the dominant intraprostatic lesion and dose analysis
      of volumetric modulated arc therapy planning for prostate cancer.
AB  - PURPOSE: Primary radiation therapy is a curative treatment option for prostate
      cancer. The aim of this study was to evaluate the detection of the dominant
      intraprostatic lesion (DIL) with magnetic resonance imaging (MRI) for
      radiotherapy treatment planning, the comparison with transrectal ultrasound
      (TRUS)-guided biopsies and the examination of the dose distribution in relation
      to the DIL location. MATERIALS AND METHODS: In all, 54 patients with treatment
      planning MRI for primary radiotherapy of prostate cancer from 03/2015 to 03/2017
      at the Universitatsklinikum Wurzburg were identified. The localization of the DIL
      was based on MRI with T2- and diffusion-weighted imaging. After registration of
      the MR image sets within Pinnacle3 (Philips Radiation Oncology Systems,
      Fitchburg, WI, USA), the dose distribution was analyzed. The location of the DIL
      was compared to the pathology reports in a side-based manner. RESULTS: The DIL
      mean dose (Dmean) was 77.51 +/- 0.77 Gy and in 50/51 cases within the tolerance
      range or exceeded the prescribed dose. There was a significant difference in
      Dmean between ventral (n = 21) and dorsal (n = 30) DIL (77.87 +/- 0.67 vs. 77.26
      +/- 0.77 Gy; p = 0.005). MRI-guided localization showed an accuracy and
      sensitivity of up to 78.8% and 82.1% for inclusion of secondary lesions,
      respectively. CONCLUSION: Up to 82.1% of histologically verified intraprostatic
      lesions were identified in the context of MRI-guided radiotherapy treatment
      planning. As expected, dorsal DIL tend to be minimally underdosed in comparison
      to ventral DIL. Adequate dose coverage was achieved in over 98% of patients.

PMID- 30209534
TI  - Role of mGlu2 in the 5-HT2A receptor-dependent antipsychotic activity of
      clozapine in mice.
AB  - BACKGROUND: Serotonin 5-HT2A and metabotropic glutamate 2 (mGlu2) are
      neurotransmitter G protein-coupled receptors (GPCRs) involved in the signaling
      mechanisms underlying psychosis and schizophrenia treatment. Previous findings in
      mGlu2 knockout (KO) mice suggested that mGlu2 is necessary for head-twitch
      behavior, a rodent phenotype characteristic of hallucinogenic 5-HT2A receptor
      agonists. However, the role of mGlu2 in the behavioral effects induced by
      antipsychotic drugs remains poorly understood. Here, we tested antipsychotic-like
      behavioral phenotypes induced by the atypical antipsychotic clozapine in mGlu2-KO
      mice and wild-type control littermates. METHODS: Locomotor activity was tested in
      mGlu2-KO mice and control littermates injected (i.p.) with clozapine (1.5 mg/kg)
      or vehicle followed by MK801 (0.5 mg/kg), PCP (7.5 mg/kg), amphetamine (6 mg/kg),
      scopolamine (2 mg/kg), or vehicle. Using a virally (HSV) mediated transgene
      expression approach, the role of frontal cortex mGlu2 in the modulation of MK801
      induced locomotor activity by clozapine treatment was also evaluated. RESULTS:
      The effect of clozapine on hyperlocomotor activity induced by the dissociative
      drugs MK801 and phencyclidine (PCP) was decreased in mGlu2-KO mice as compared to
      controls. Clozapine treatment, however, reduced hyperlocomotor activity induced
      by the stimulant drug amphetamine and the deliriant drug scopolamine in both wild
      type and mGlu2-KO mice. Virally mediated over-expression of mGlu2 in the frontal
      cortex of mGlu2-KO mice rescued the ability of clozapine to reduce MK801-induced
      hyperlocomotion. CONCLUSION: These findings further support the existence of a
      functionally relevant crosstalk between 5-HT2A and mGlu2 receptors in different
      preclinical models of antipsychotic activity.

PMID- 30209536
TI  - Facial perception of infants with cleft lip and palate with/without the NAM
      appliance.
AB  - OBJECTIVE: This study aimed to assess adults' subjective perception of infants
      with a unilateral cleft lip and palate (UCLP) with and without a nasoalveolar
      molding (NAM) appliance compared to those of controls concerning (1) adult gaze
      patterns and (2) emotional valence. METHODS: This interdisciplinary study was
      performed by (1) the Department of Orthodontics and (2) the Department for
      Psychiatry and Psychotherapy, University Medical Center Goettingen, using eye
      tracking and a 10-point Likert scale questionnaire. Eye movements and valence
      rating of 30 unaffected adults (15 women, 15 men; mean age: 25.5 years, standard
      deviation [SD] = 7.5) were recorded while presenting them infants in three
      picture categories (1) infant with UCLP, (2) infant with UCLP and inserted NAM
      appliance and (3) infant without UCLP. Total fixation time in two main areas of
      interest (AOI upper/lower face) was measured according to picture category as
      well as participants' valence rating regarding infants' appearance. RESULTS: In
      pictures of infants with UCLP or UCLP and NAM appliance participants had longer
      fixation times on AOI lower face compared to reconstructed pictures of infants
      without UCLP. No significant effect of a NAM appliance on gaze patterns could be
      detected. The valence of pictures of infants with UCLP was rated more negative
      compared to pictures of unaffected infants. An inserted NAM appliance improved
      this rating. CONCLUSIONS: The results bolster the assumption that facial
      disruptions like UCLP alter adults' perception of infants. Even though the NAM
      appliance is not able to re-establish usual adult gaze patterns, it can help to
      improve adults' emotional assessment.

PMID- 30209537
TI  - Superiority vs. equivalence/non-inferiority: study design and meeting abstracts.

PMID- 30209538
TI  - Immunological biomarkers for the development and progression of type 1 diabetes.
AB  - Immune biomarkers of type 1 diabetes are many and diverse. Some of these, such as
      the autoantibodies, are well established but not discriminative enough to deal
      with the heterogeneity inherent to type 1 diabetes progression. As an
      alternative, high hopes are placed on T cell assays, which give insight into the
      cells that actually target the beta cell or play a crucial role in maintaining
      tolerance. These assays are approaching a level of robustness that may allow for
      solid conclusions on both disease progression and therapeutic efficacy of immune
      interventions. In addition, 'omics' approaches to biomarker discovery are rapidly
      progressing. The potential emergence of novel biomarkers creates a need for the
      introduction of bioinformatics and 'big data' analysis systems for the
      integration of the multitude of biomarker data that will be available, to
      translate these data into clinical tools. It is worth noting that it is unlikely
      that the same markers will apply to all individuals. Instead, individualised
      signatures of biomarkers, combining autoantibodies, T cell profiles and other
      biomarkers, will need to be used to classify at-risk patients into various
      categories, thus enabling personalised prediction, prevention and treatment
      approaches. To achieve this goal, the standardisation of assays for biomarker
      discovery, the integration of analyses and data from biomarker studies and, most
      importantly, the careful clinical characterisation of individuals providing
      samples for these studies are critical. Longitudinal sample-collection
      initiatives, like INNODIA, should lead to novel biomarker discovery, not only
      providing a better understanding of type 1 diabetes onset and progression, but
      also yielding biomarkers of therapeutic efficacy of interventions to prevent or
      arrest type 1 diabetes.

PMID- 30209540
TI  - Radial artery aneurysm secondary to dynamic entrapment by extensor pollicis
      longus tendon: a case of snapping thumb.
AB  - Aneurysms of the distal radial artery at the level of the wrist are rare. Most
      reported cases are posttraumatic, either from iatrogenic arterial puncture for
      radial arterial access or from a penetrating injury. Other causes include
      infection and connective tissue disorders. Early diagnosis is important to avoid
      the potential complications of thrombus formation, distal digital ischemia, and
      rupture. Evaluation of the radial artery is typically performed using non
      invasive modalities like ultrasonography, computed tomographic angiography (CTA),
      and magnetic resonance angiography (MRA). Invasive angiography can also be
      performed, particularly if minimally invasive treatment options are being
      considered. We report a case of a 35-year-old male mechanic who presented with
      pain at the base of the left thumb dorsally, with reproducible painful snapping
      on dynamic exam. Ultrasound demonstrated a fusiform aneurysm of the radial
      artery. At the level of the aneurysm, there was dynamic entrapment of the artery
      between the extensor pollicis longus (EPL) tendon and the underlying trapezium.
      The patient's symptoms improved with conservative management and avoidance of the
      snapping-producing maneuvers. To our knowledge, this is the first published case
      of snapping at the base of the thumb resulting in repetitive entrapment of the
      radial artery by the EPL tendon captured on dynamic ultrasound examination.

PMID- 30209542
TI  - Comparison of extracolonic findings and clinical outcomes in a screening and
      diagnostic CT colonography population.
AB  - PURPOSE: To compare the distribution of extracolonic findings and clinical
      outcomes between screening and diagnostic CT colonography (CTC) populations.
      METHODS: 388 consecutive patients (369 men, 19 women; mean +/- SD age 67.8 +/- 10
      years) who underwent first-time CTC (4/2011-4/2017) at a Veteran's Affairs
      Medical Center were divided into screening (asymptomatic) or diagnostic
      (symptomatic) cohorts based on CTC indication. CTC reporting and data system E
      scores for extracolonic findings were retrospectively assigned based on
      prospective CTC radiologic reports. Multinomial logistic regression was used to
      examine the association between E-scores and CTC indication. Electronic medical
      records of all patients with E3 or E4 scores were reviewed (median follow-up 2.8
      years) to determine clinical outcomes. RESULTS: 68% (262/388) underwent screening
      and 32% (126/388) diagnostic CTC. 7.2% (28/388) had extracolonic findings
      considered potentially significant (E4), 4.4% (17/388) had indeterminate but
      likely unimportant findings (E3), and 88.4% (347/388) had normal or unimportant
      findings (E1 or E2). E-scores were not significantly different between screening
      and diagnostic CTC when adjusted for age, gender, and prior imaging (p = 0.44).
      4.6% (12/262) of patients with E3/E4 findings in the screening cohort
      demonstrated clinically significant outcomes, compared with 4.0% (5/126) in the
      diagnostic cohort, including a total of three extracolonic malignancies (0.8%)
      and three abdominal aortic aneurysms (0.8%). 4.6% (18/388) underwent follow-up
      imaging studies to confirm a benign outcome after detection of a category E3/E4
      finding. CONCLUSIONS: The distribution of extracolonic findings and clinical
      outcomes were not statistically significantly different between screening and
      diagnostic CTC populations.

PMID- 30209543
TI  - Second pancreas sign.

PMID- 30209539
TI  - Crosstalk of protein kinase C epsilon with Smad2/3 promotes tumor cell
      proliferation in prostate cancer cells by enhancing aerobic glycolysis.
AB  - Protein kinase C epsilon (PKCepsilon) has emerged as an oncogenic protein kinase
      and plays important roles in cancer cell survival, proliferation, and invasion.
      It is, however, still unknown whether PKCepsilon affects cell proliferation via
      glucose metabolism in cancer cells. Here we report a novel function of PKCepsilon
      that provides growth advantages for cancer cells by enhancing tumor cells
      glycolysis. We found that either PKCepsilon or Smad2/3 promoted aerobic
      glycolysis, expression of the glycolytic genes encoding HIF-1alpha, HKII, PFKP
      and MCT4, and tumor cell proliferation, while overexpression of PKCepsilon or
      Smad3 enhanced aerobic glycolysis and cell proliferation in a protein kinase D-
      or TGF-beta-independent manner in PC-3M and DU145 prostate cancer cells. The
      effects of PKCepsilon silencing were reversed by ectopic expression of Smad3.
      PKCepsilon or Smad3 ectopic expression-induced increase in cell growth was
      antagonized by inhibition of lactate transportation. Furthermore, interaction of
      endogenous PKCepsilon with Smad2/3 was primarily responsible for phosphorylation
      of Ser213 in the Samd3 linker region, and resulted in Smad3 binding to the
      promoter of the glycolytic genes, thereby promoting cell proliferation. Forced
      expression of mutant Smad3 (S213A) attenuated PKCepsilon-stimulated protein
      overexpression of the glycolytic genes. Thus, our results demonstrate a novel
      PKCepsilon function that promotes cell growth in prostate cancer cells by
      increasing aerobic glycolysis through crosstalk between PKCepsilon and Smad2/3.

PMID- 30209545
TI  - [Journal Club].

PMID- 30209544
TI  - Sweating distribution and active sweat glands on the scalp of young males in hot
      dry and hot-humid environments.
AB  - PURPOSE: We investigated the effects of humidity on regional sweating secretion
      and active sweat gland density on the scalp during passive heating in hot
      environments. METHODS: Eight male subjects shaved their heads prior to expose to
      dry (30%RH; H30%) and humid (85%RH; H85%) conditions at an air temperature of 32 
      degrees C. Total sweat rate, local sweat rates (frontal, vertex, temporal, and
      occipital regions), active sweat glands on the scalp (2 frontal, 2 parietal, 2
      temporal, 1 occipital, and 1 vertex), and rectal and skin temperatures were
      measured during leg immersion in 42  degrees C water for 60 min. RESULTS: (1)
      Total sweat rates were greater for H30% (179.4 +/- 35.6 g h-1) than for H85%
      (148.1 +/- 27.2 g h-1) (P < 0.05). (2) Scalp sweat secretion tended to be greater
      in the H85% than the H30%. (3) Head sweat rates were greater on the frontal than
      on the vertex for both humidity conditions (P < 0.05). (4) Active sweat gland
      density on the scalp was greater for H85% (82 +/- 13 glands cm-2) than for H30%
      (62 +/- 17 glands cm-2) (P < 0.05). (5) No significant difference was found in
      rectal temperature between H30% and H85%, whereas mean skin temperature was
      significantly lower for H30% (34.8 +/- 0.7  degrees C) than for the H85%
      condition (36.0 +/- 0.3  degrees C) (P < 0.05). CONCLUSIONS: These results
      indicate that the thermoregulatory sweating responses for the scalp region were
      significantly increased in the hot-humid condition compared to the hot-dry
      condition. Among the regions on the scalp surface, the vertex was the least
      sensitive to the change in humidity.

PMID- 30209546
TI  - Picket-fences in the plasma membrane: functions in immune cells and phagocytosis.
AB  - Recent studies of molecular mobility in the plasma membrane have revealed that
      diffusion is restricted by cytoskeletal networks or fences. Transmembrane protein
      "pickets" that reversibly associate with the membrane-associated skeleton and
      with the pericellular coat impede the movement of unattached bystander molecules.
      While membrane picket-fences were originally described as barriers to free
      diffusion in more passive cell types such as fibroblasts, they have particularly
      important functions in the more dynamic immune cells. In phagocytes, such fences
      curtail spontaneous activation and their disassembly facilitates stimulation by
      target particles, fostering receptor clustering and the exclusion of phosphatases
      from the phagocytic cup. In this review, we describe the nature of the cellular
      cytoskeleton and of the exoskeleton created by the pericellular coat, their
      association with transmembrane pickets, and the modulation of molecular mobility
      during phagocytosis.

PMID- 30209548
TI  - Streptococcus suis biofilm: regulation, drug-resistance mechanisms, and
      disinfection strategies.
AB  - Streptococcus suis (S. suis) is a major swine pathogen and an important zoonotic
      agent. Like most pathogens, the ability of S. suis to form biofilms plays a
      significant role in its virulence and drug resistance. A better understanding of
      the mechanisms involved in biofilm formation by S. suis as well as of the methods
      to efficiently remove and kill biofilm-embedded bacteria can be of high interest
      for the prevention and treatment of S. suis infections. The aim of this
      literature review is to update our current knowledge of S. suis biofilm
      formation, regulatory mechanisms, drug-resistance mechanisms, and disinfection
      strategies.

PMID- 30209549
TI  - Fungal mitochondrial genomes and genetic polymorphisms.
AB  - Mitochondria are the powerhouses of eukaryotic cells, responsible for ATP
      generation and playing a role in a diversity of cellular and organismal
      functions. Different from the majority of other intracellular membrane
      structures, mitochondria contain their own genetic materials that are capable of
      independent replication and inheritance. In this mini-review, we provide brief
      summaries of fungal mitochondrial genome structure, size, gene content,
      inheritance, and genetic variation. We pay special attention to the relative
      genetic polymorphisms of the mitochondrial vs nuclear genomes at the population
      level within individual fungal species. Among the 20 species/groups of species
      reviewed here, there is a range of variation among genes and species in the
      relative nuclear and mitochondrial genetic polymorphisms. Interestingly, most
      (15/20) showed a greater genetic diversity for nuclear genes and genomes than for
      mitochondrial genes and genomes, with the remaining five showing similar or
      slower nuclear genome genetic variations. This fungal pattern is different from
      the dominant pattern in animals, but more similar to that in plants. At present,
      the mechanisms for the variations among fungal species and the overall low level
      of mitochondrial sequence polymorphisms are not known. The increasing
      availability of population genomic data should help us reveal the potential
      genetic and ecological factors responsible for the observed variations.

PMID- 30209550
TI  - Insertion of antihypertensive peptides in acidic subunit from amaranth 11S
      induces contrasting effects in stability.
AB  - The insertion of peptides is a biotechnology tool widely used to improve the
      nutraceutical properties of proteins. Because the effect of these insertions in
      protein stability and function is difficult to predict, it should be determined
      experimentally. In this study, we created two variants of amarantin acidic
      subunit and analyzed them along with other four proteins reported previously. We
      measured their response against two destabilizing agents: temperature and urea.
      The six proteins presented the insertion of antihypertensive peptides (VYVYVYVY
      or RIPP) in the variable regions of the protein. We observed that their effect
      strongly depended on the site of the insertion. The insertion in the variable
      region I stabilized the protein both thermally and chemically, but it affected
      the inhibitory activity of the angiotensin-converting enzyme in vitro. In
      contrast, insertions in other three regions were severely destabilizing,
      producing molten globules. Our findings reveal that the insertion of bioactive
      peptides in variable regions of a protein can increase or decrease the protein's
      thermal and chemical stability and that these conformational changes may also
      alter its final activity.

PMID- 30209547
TI  - Extracellular vesicles in cancer immune responses: roles of purinergic receptors.
AB  - Extracellular vesicles (EVs) are nano- to micro-scale membrane-enclosed vesicles
      that are released from presumably all cell types. Tumor cells and immune cells
      are prodigious generators of EVs often with competing phenotypes in terms of
      immune suppression versus immune stimulation. Purinergic receptors, proteins that
      bind diverse purine nucleotides and nucleosides (ATP, ADP, AMP, adenosine), are
      widely expressed across tissues and cell types, and are prominent players in
      immune and tumor cell nucleotide metabolism. The effects of purinergic receptor
      stimulation or agonism tend to produce inflammatory responses that may aid immune
      stimulation but may also provoke various immune suppression mechanisms,
      particularly in the tumor microenvironment. EVs released by cells following
      receptor stimulation are frequently pro-inflammatory, but often also pro
      thrombolytic; these EVs may generate an environment that favors tumor progression
      at the cost of an effective immune response. Purinergic signaling pathways are
      becoming more recognized as valuable targets in various therapeutic scenarios,
      including cancer. It is possible that some of those clinically relevant compounds
      might also impact EV secretion and/or phenotype, which would hopefully capitalize
      on the immune stimulatory properties of purinergic signaling while minimizing the
      immune suppressive consequences. This review covers a relatively understudied
      area in EV biology, but even so, focuses almost exclusively on the purinergic
      receptors in a very limited capacity. There is much more to evaluate and
      incorporate into our understanding of extracellular nucleotides in EV biology,
      and we hope this work prompts further discovery.

PMID- 30209551
TI  - Gene cloning and seamless site-directed mutagenesis using single-strand annealing
      (SSA).
AB  - The full length of interested genes can be usually cloned by assembling exons or
      RACE products through overlap PCR. However, the procedure requires multiple PCR
      steps, which are prone to random mutagenesis. Here, we present a novel SSA-based
      method for gene cloning and seamless site-directed mutagenesis. We firstly cloned
      the full-length coding sequence of Cashmere goat (Capra hircus) Hoxc13 gene by
      assembling exons amplified from genomic DNA. Secondly, we created a Hoxc13 loss
      function mutant seamlessly and further illustrated that direct repeat length of
      25 bp is enough to trigger the SSA repair in routine E. coli strains including
      DH5alpha, Trans1t1, JM109, and Top10. Moreover, we cloned another full-length
      mutant of Foxn1 gene from Cashmere goat cDNA using further shortened direct
      repeats of 19 bp. In summary, our study provided an alternative method to
      overcome the difficulties during overlap PCR in some particular cases for gene
      cloning.

PMID- 30209553
TI  - Renal cell carcinoma: standards and controversies.

PMID- 30209552
TI  - RUSSCO-RSP comparative study of immunohistochemistry diagnostic assays for PD-L1
      expression in urothelial bladder cancer.
AB  - In this collaborative study by the Russian Society of Clinical Oncology and the
      Russian Society of Pathology, we assessed the concordance among three validated,
      commercially available PD-L1 immunohistochemistry assays for patients with
      urothelial cancer. Tumors from 100 urothelial cancer patients were stained with
      the antibody clones 22C3 (Agilent), SP142 (Ventana Medical Systems), and SP263
      (Ventana Medical Systems), which are used in clinical trials of second-line
      therapy with checkpoint inhibitors. Four trained pathologists independently
      evaluated the percentages of tumor cells (TC) and tumor-infiltrating immune cells
      (IC) that were stained at any intensity by each of the antibodies. The test
      specific cutoffs for the proportions of stained cells in a positive sample were
      pre-specified as TC + IC >= 10% or TC >= 10% for 22C3, IC >= 5% for SP142, and TC
      >= 25% or IC >= 25% for SP263. Three hundred immunohistochemistry slides were
      scored. The percentages of PD-L1 staining in the three assays without using any
      cutoff were higher in the IC than in the TC (55% versus 24% for 22C3, 45% versus
      8% for SP142, and 72% versus 27% for SP263, respectively). The Pearson
      correlation coefficients for anti-PD-L1 staining in the IC were 0.5, 0.69, and
      0.85 with 22C3/SP142, 22C3/SP263, and SP142/SP263, respectively. The Pearson
      correlation coefficients for PD-L1 staining in the TC were 0.93, 0.99, and 0.91
      for the same pairs. Among the patients who were negative for PD-L1 staining by
      one test, 91-100% were also negative by the other tests. Among the patients who
      were positive by one test, 43-100% were also positive by the other tests. Our
      data indicate that repeated testing can be avoided as a patient with urothelial
      cancer who is classified as negative for PD-L1 expression by one of the three
      single tests using the corresponding cutoff rule is highly likely (91-100%) to be
      classified as negative by either of the other tests.

PMID- 30209554
TI  - Correction to: Electroacupuncture induces antihyperalgesic effect through
      endothelin-B receptor in the chronic phase of a mouse model of complex regional
      pain syndrome type I.
AB  - The original version of this article contains an error. The Author Francisco Jose
      Cidral-Filho incorrectly listed as Francisco Jose Cidra-Filho. The correct
      spelling is presented above. The original article has been corrected.

PMID- 30209555
TI  - Alcohol intake and risk of rheumatoid arthritis: a Mendelian randomization study.
AB  - OBJECTIVE: To examine whether alcohol intake is causally associated with
      rheumatoid arthritis (RA). METHODS: We performed a two-sample Mendelian
      randomization (MR) analysis using the inverse-variance weighted (IVW), weighted
      median, and MR-Egger regression methods. We used the publicly available summary
      statistics of alcohol intake frequency from the UK Biobank genome-wide
      association studies (GWASs; n = 336,965) as the exposure and a GWAS meta-analysis
      of 5539 autoantibody-positive RA patients and 20,169 controls as the outcome.
      RESULTS: We selected 24 single nucleotide polymorphisms (SNPs) associated with
      alcohol intake frequency at genome-wide significance as instrumental variables
      (IVs) to improve inference, 16 of which were inversely associated with RA. The
      IVW method showed no evidence of a causal association between alcohol intake and
      RA (beta = 0.218, SE = 0.213, p = 0.306). The MR-Egger regression revealed that
      directional pleiotropy was unlikely to bias the result (intercept = 0.027, p =
      0.292). The MR-Egger analysis and the weighted median approach showed no causal
      association between alcohol intake and RA (beta = -0.778, SE = 0.947, p = 0.420
      and beta = -0.286, SE = 0.302, p = 0.344, respectively). Cochran's Q test did not
      indicate heterogeneity between IV estimates based on the individual variants, and
      results from a "leave-one-out" analysis demonstrated that no single SNP was
      driving the IVW point estimate. CONCLUSION: The MR analysis does not support a
      causal inverse association between alcohol intake and RA occurrence.

PMID- 30209556
TI  - Gemcitabine, cisplatin, and dexamethasone (GDP) in combination with methotrexate
      and pegaspargase is active in newly diagnosed peripheral T cell lymphoma
      patients: a phase 2, single-center, open-label study in China.
AB  - Peripheral T cell lymphomas (PTCL) are less responsive to anthracycline
      containing regimen such as CHOP and carry a poor prognosis. In this prospective
      study, we investigated gemcitabine, cisplatin, and dexamethasone (GDP) combined
      with methotrexate (MTX) and pegaspargase (PEG-L) as front-line treatment in PTCL.
      Eligible newly diagnosed PTCL patients received 4 cycles of the GDP-ML
      chemotherapy every 28 days. After 4 cycles, responding patients continued to
      receive either autologous stem cell transplantation or the MTX/cytarabine (MA)
      regimen for consolidation. This trial is registered with www.chictr.org.cn
      (ChiCTR-ONC-12002055). A total of 65 patients were enrolled with a median follow
      up of 38.5 months. The overall response rate (ORR) was 55.4%, and complete
      remission rate (CR) was 33.8%. The median overall survival (OS) was 16 months,
      and the 1-year and 2-year OS were 59.1% and 38.2%, respectively. The median PFS
      was only 8 months. The main adverse event was hematologic toxicity: 50% patients
      showed grade III/IV neutropenia. GDP-ML for the first-line treatment of PTCL
      patients is an effective induction regimen compared with standard CHOP, and the
      toxicity was more significant but acceptable. However, future studies exploring
      new drug combinations are warranted to overcome relapse after remission.
      ClinicalTrials.gov Identifier: NCT02987244.

PMID- 30209557
TI  - Nitric oxide metabolites in hypoxia, freezing, and hibernation of the wood frog,
      Rana sylvatica.
AB  - Nitric oxide (NO) is a gaseous free radical that in diverse organisms performs
      many signaling and protective functions, such as vasoregulation, inhibition of
      apoptosis, antioxidation, and metabolic suppression. Increased availability of NO
      may be especially important during life-history periods when organisms contend
      with multiple stresses. We investigated dynamics of the NO metabolites, nitrite
      (NO2-) and nitrate (NO3-), in the blood plasma, heart, liver, and skeletal muscle
      of the wood frog (Rana sylvatica), an amphibian that endures chronic cold,
      freezing, hypoxia, dehydration, and extended aphagia during hibernation. We found
      elevated concentrations of NO2- and/or NO3- in the plasma (up to 4.1-fold), heart
      (3.1-fold), and liver (up to 4.1-fold) of frogs subjected to experimental hypoxia
      (24 h, 4  degrees C), and in the liver (up to 3.8-fold) of experimentally frozen
      frogs (48 h, - 2.5  degrees C), suggesting that increased NO availability aids in
      survival of these stresses. During a 38-week period of simulated hibernation, NO2
      and/or NO3- increased in the plasma (up to 10.4-fold), heart (up to 3.3-fold),
      and liver (5.0-fold) during an initial 5-week winter-acclimatization regimen and
      generally remained elevated thereafter. In hibernation, plasma NO2- was higher in
      frogs indigenous to Interior Alaska than in conspecifics from a temperate locale
      (southern Ohio), suggesting that NO availability is matched to the severity of
      environmental conditions prevailing in winter. The comparatively high NO
      availability in R. sylvatica, a stress-tolerant species, together with published
      values for other species, suggest that the NO protection system is of general
      importance in the stress adaptation of vertebrates.

PMID- 30209559
TI  - Ecological Effects of Single-Walled Carbon Nanotubes on Soil Microbial
      Communities and Soil Fertility.
AB  - The manufacturers of single-walled carbon nanotubes (SWCNTs) are continuously
      expanding their manufacturing and commercial markets, indicating that the
      environmental release and accumulation of SWCNTs in soil is inevitable. However,
      little is known about the effects of SWCNTs on soil physicochemical properties
      and soil microbial communities. Our results showed that treatment with SWCNTs
      resulted in an enhancement of microorganism metabolism related to soil organic
      compound degradation and a change in the structure of soil microbial communities,
      but the diversity of soil microorganisms was not significantly affected. The
      decrease in soil urease activity and the increase in the relative abundance of
      Nitrospirae after SWCNTs exposure might be relevant to the induction of soil
      nitrification. The relative abundances of phosphate-solubilizing microorganisms
      increased after exposure to SWCNTs, which was beneficial for phosphorus
      bioavailability in the soil. Our current study highlights that exposure to SWCNTs
      at concentrations of 3 and 10 ug/g can change the composition of soil
      microorganism communities, promote soil organic degradation and improve soil
      fertility by enhancing N and P availability in a short time.

PMID- 30209558
TI  - Heavy Metal Pollution Characteristics in the Modern Sedimentary Environment of
      Northern Jiaozhou Bay, China.
AB  - The particle size distribution characteristics of sediments and the
      concentrations of heavy metals in Jiaozhou Bay were investigated in this study.
      The average concentrations of Cu, Pb, Zn, Cr, Cd, Hg and As were 36.88, 29.60,
      82.08, 77.48, 0.083, 0.048 and 11.00 mg/kg, respectively. The heavy metal
      concentrations were highest in the eastern sediments, followed by those at the
      top of the bay, and the lowest concentrations were observed in the central
      region. Overall, a decreasing trend from the center of the bay to the periphery
      was observed. Additionally, the distribution of heavy metals in sediments was not
      completely controlled by sediment particle size. The degree of heavy metal
      contamination was evaluated using the geoaccumulation index and Hakanson's
      method. The results revealed that the level of heavy metal pollution in the
      sediments was relatively low and that the main pollution elements were Cu and Hg.
      In addition, the sediments are associated with various levels of potential
      ecological risk due to the high pollution levels of Hg and Cd.

PMID- 30209561
TI  - Tongue-Strengthening Exercises in Healthy Older Adults: Does Exercise Load
      Matter? A Randomized Controlled Trial.
AB  - Tongue-strengthening exercises (TSE) are based on the principles of exercise and
      motor learning, including intensity. Intensity is manipulated by gradually
      adjusting the resistive load. This randomized controlled trial (RCT) investigates
      the effect of three different values resistive load during TSE in healthy older
      adults. Sixty subjects completed 8 weeks of TSE while exercising with Iowa Oral
      Performance Instrument (IOPI). They were randomly distributed to 4 different
      treatment arms: 3 exercise groups (EG1: n = 15; EG2: n = 16, EG3: n = 16) and 1
      control group performing lip-strengthening exercises (CG: n = 13). Values of
      resistive load for EG1, EG2, and EG3 were 100, 80, and 60% 1RM, respectively.
      Anterior and posterior maximal isometric pressures (MIPA, MIPP) were measured at
      baseline, after 4 and 8 weeks of training and 4 weeks post-training. MIPA and
      MIPP in the EG were significantly higher than in the CG at all time points,
      except baseline. No significant differences between EG were found, but some
      trends were observable. Anteriorly, the higher the resistive load, the higher the
      increase in MIP. Posteriorly, 100% 1RM caused the highest values, followed by 60%
      and 80% 1RM. No detraining effects were measured. The degree of exercise load had
      a significant negative effect on the registered success rate. This RCT confirms
      the efficacy of TSE in healthy older adults. For MIPA and MIPP, TSE at a
      resistive load of 100% 1RM are the most efficient choice in this population,
      while lowering the resistive load will lead to an increased success rate. No
      detraining effects were registered.

PMID- 30209560
TI  - Primary parotid carcinoma: analysis of risk factors and validation of a
      prognostic index.
AB  - OBJECTIVES: Primary cancer of the parotid gland (PG) is a rare disease
      characterized by a wide variety of histologies and subtypes. The aim of the study
      was to identify factors influencing survival and validate the prognostic scores
      (PS1 and PS2) by Vander Poorten et al. STUDY DESIGN: Retrospective cohort study.
      METHODS: All patients with previously untreated PG epithelial malignancies who
      underwent surgery with curative intent from 2002 to 2015 at a single center were
      retrospectively reviewed. RESULTS: 104 patients were included. Mean age was 60.2
      years (range 14-88). Definitive pT staging was: 26 (25%) pT1, 19 (18.3%) pT2, 15
      (14.4%) pT3, 41 (39.4%) pT4a, and 3 (2.9%) pT4b. Lateral neck nodal metastases
      were diagnosed in 27 (26%) patients. Five- and 10-year overall survival was 74.7%
      and 69.4%, respectively. Disease-specific survival at 5 and 10 years was 80.4%
      and 76.5%, respectively. Recurrence-free survival at 5 and 10 years was 66.9%. PS
      1 and PS-2 scores correlated with prognosis. The most critical prognostic
      variables were grading, nodal metastases, perineural infiltration, lympho
      vascular invasion, and skin infiltration. CONCLUSIONS: Major risk factors in
      primary PG carcinomas can effectively identify high-risk patients. The prognostic
      score by Vander Poorten et al. is a highly reliable tool to predict the
      prognostic profile.

PMID- 30209562
TI  - An Exploratory Study of Hyoid Visibility, Position, and Swallowing-Related
      Displacement in a Pediatric Population.
AB  - Hyoid position and swallowing-related displacement has been studied in healthy
      adults and adults with dysphagia, but research is limited in children. The aim of
      this study was to investigate feasibility of visualizing and measuring position
      and swallowing-related displacement of the hyoid bone in children. We explored
      relationships between hyoid displacement, age and aspiration risk scores.
      Pediatric swallowing data were extracted from a videofluoroscopy database
      containing recordings from 133 children aged 9 days to 21 years (mean 36 months,
      SD 3 years) referred for videofluoroscopy due to concerns regarding their
      feeding. Children presented with varying etiologies: neurological, structural,
      respiratory, and other diagnoses. Still shot images were extracted for the frame
      of hyoid peak position and a frame showing the hyoid at rest. Pixel-based image
      analysis software was used to measure hyoid position in three directions (X =
      anterior, Y = superior, XY = hypotenuse) relative to C4 vertebra. Difference
      between rest and peak position was used to measure hyoid displacement (X, Y and
      XY). The hyoid was not visible in children < 9 months, but could be reliably
      visualized and measured in 49 children. Descriptive statistics were collected for
      hyoid parameters. Age was significantly associated with rest (Y and XY) and peak
      (Y and XY) hyoid position parameters as well as anterior displacement. No
      significant associations were observed between hyoid parameters and aspiration
      risk scores. This study successfully explored hyoid visibility, position and
      swallowing-related displacement in a pediatric population. Hyoid can be reliably
      visualized and tracked through videofluoroscopy in children > 9 months of age.

PMID- 30209563
TI  - Cardiovascular regulation in response to multiple hemorrhages: analysis and
      parameter estimation.
AB  - Mathematical models can provide useful insights explaining behavior observed in
      experimental data; however, rigorous analysis is needed to select a subset of
      model parameters that can be informed by available data. Here we present a method
      to estimate an identifiable set of parameters based on baseline left ventricular
      pressure and volume time series data. From this identifiable subset, we then
      select, based on current understanding of cardiovascular control, parameters that
      vary in time in response to blood withdrawal, and estimate these parameters over
      a series of blood withdrawals. These time-varying parameters are first estimated
      using piecewise linear splines minimizing the mean squared error between measured
      and computed left ventricular pressure and volume data over four consecutive
      blood withdrawals. As a final step, the trends in these splines are fit with
      empirical functional expressions selected to describe cardiovascular regulation
      during blood withdrawal. Our analysis at baseline found parameters representing
      timing of cardiac contraction, systemic vascular resistance, and cardiac
      contractility to be identifiable. Of these parameters, vascular resistance and
      cardiac contractility were varied in time. Data used for this study were measured
      in a control Sprague-Dawley rat. To our knowledge, this is the first study to
      analyze the response to multiple blood withdrawals both experimentally and
      theoretically, as most previous studies focus on analyzing the response to one
      large blood withdrawal. Results show that during each blood withdrawal both
      systemic vascular resistance and contractility decrease acutely and partially
      recover, and they decrease chronically across the series of blood withdrawals.

PMID- 30209564
TI  - Cancer Immunotherapy: A Simple Guide for Interventional Radiologists of New
      Therapeutic Approaches.
AB  - The therapeutic options in the treatment of cancer therapy have been recently
      significantly increased with systemic immune-targeted therapies. Novel
      immunotherapy approaches based on immune checkpoint blockade or engineered
      cytotoxic T lymphocytes have reached late-stage clinical development, with highly
      encouraging results. The success of cancer immunotherapy has generated a
      tremendous interest in further developing and exploring these strategies in
      combination with other approaches such as radiotherapy and local ablative
      therapies in oncology. The goal of this review is to discuss current approaches
      in immunotherapy and provide simple and constructive explanations on their
      mechanisms of action as well as certain more common and serious toxicities.

PMID- 30209565
TI  - Intranasal co-administration of recombinant active fragment of Zonula occludens
      toxin and truncated recombinant EspB triggers potent systemic, mucosal immune
      responses and reduces span of E. coli O157:H7 fecal shedding in BALB/c mice.
AB  - Escherichia coli O157:H7 with its traits such as intestinal colonization and
      fecal-oral route of transmission demands mucosal vaccine development. E. coli
      secreted protein B (EspB) is one of the key type III secretory system (TTSS)
      targets for mucosal candidate vaccine due to its indispensable role in the
      pathogenesis of E. coli O157:H7. However, mucosally administered recombinant
      proteins have low immunogenicity which could be overcome by the use of mucosal
      adjuvants. The quest for safe, potent mucosal adjuvant has recognized DeltaG
      fragment of Zonula occludens toxin of Vibrio cholerae with such properties.
      DeltaG enhances mucosal permeability via the paracellular route by altering
      epithelial tight junction structure in a reversible, ephemeral and non-toxic
      manner. Therefore, we tested whether recombinant DeltaG intranasally co
      administered with truncated EspB (EspB + DeltaG) could serve as an effective
      mucosal adjuvant. Results showed that EspB + DeltaG group induced higher systemic
      IgG and mucosal IgA than EspB alone. Moreover, EspB alone developed Th2 type
      response with IgG1/IgG2a ratio (1.64) and IL-4, IL-10 cytokines whereas that of
      EspB + DeltaG group generated mixed Th1/Th2 type immune response evident from
      IgG1/IgG2a ratio (1.17) as well as IL-4, IL-10 and IFN-gamma cytokine levels
      compared to control. Sera of EspB + DeltaG group inhibited TTSS mediated
      haemolysis of murine RBCs more effectively compared to EspB, control group and
      sera of both EspB + DeltaG, EspB group resulted in similar levels of efficacious
      reduction in E. coli O157:H7 adherence to Caco-2 cells compared to control.
      Moreover, vaccination with EspB + DeltaG resulted in significant reduction in E.
      coli O157:H7 fecal shedding compared to EspB and control group in experimentally
      challenged streptomycin-treated mice. These results demonstrate mucosal
      adjuvanticity of DeltaG co-administered with EspB in enhancing overall
      immunogenicity to reduce E. coli O157:H7 shedding.

PMID- 30209567
TI  - Optical coherence tomography angiography assessment of the macular capillary
      plexus after surgery for macula-off rhegmatogenous retinal detachment.

PMID- 30209566
TI  - Electromagnetic Navigation Bronchoscopy: Where Are We Now? Five Years of a Single
      Center Experience.
AB  - INTRODUCTION: Electromagnetic navigation (ENB) is a guidance tool used in the
      diagnosis of solitary pulmonary nodules (SPNs) and masses. Its diagnostic yield
      is highly variable (38-71%) and a recent study has put in doubt the role of ENB
      in sampling SPNs in a real-life setting. The aim of this study is to describe the
      5-year experience of our center with ENB, analyzing the population, possible
      confounding factors, and the diagnostic yield and accuracy of this technique.
      METHODS: We conducted a retrospective observational study including all
      consecutive patients who underwent ENB for SPNs and masses from January 2011 to
      December 2015. RESULTS: We included 113 patients; 79% had SPNs, 21% masses. The
      majority were localized in the upper and middle lobes (80%) and 61% presented a
      bronchus sign. 54% of the patients had a previous negative fluoroscopy-guided
      bronchoscopy. ENB achieved the diagnosis in 78 patients (69%) with 64 malignant
      and 14 were benign lesions. The diagnostic yield and accuracy of ENB were
      respectively 0.69 and 0.76. The only factor influencing the ability to reach a
      diagnosis was the presence of bronchus sign (p = 0.002). No procedural
      complications were reported. CONCLUSION: ENB is a safe procedure with a similar
      diagnostic yield in the real-life and research setting. Bronchus sign is an
      important factor in determining the diagnostic yield. ENB efficacy can be
      maximized by expertise and by a careful selection of each case.

PMID- 30209568
TI  - Relationship between filtering bleb vascularization and surgical outcomes after
      trabeculectomy: an optical coherence tomography angiography study.
AB  - PURPOSE: To explore the relationship between the bleb vasculature and surgical
      outcome after trabeculectomy (TRAB) using optical coherence tomography
      angiography (OCT-A). METHODS: A prospective study was conducted, which included
      26 eyes of 26 primary glaucoma patients in the final analysis. Thereinto, six
      patients underwent TRAB combined 5-FU and 12 patients received subconjunctival 5
      FU injection postoperation. The bleb vessel was evaluated using OCT-A 1 week, 2
      weeks, 1 month, 3 months, and 6 months after TRAB. Intraocular pressure (IOP),
      filtering bleb height, and bleb wall thickness were recorded at the same time.
      Pearson's correlation analysis and linear regression analysis were performed to
      determine the correlation of the vessel area data with other parameters. RESULTS:
      Compared with vessel area 1 week after surgery, there was significant increase of
      the vessel area (?vessel area) 2 weeks (11.13 +/- 11.91%, p < 0.05) and 1 month
      (16.91 +/- 14.85%, p < 0.0001) after surgery in all patients. The ?vessel area
      was significantly greater in acute angle closure (AAC) and primary angle closure
      glaucoma (PACG) 1-month post-TRAB as compared with that 1 week (p < 0.05). The
      results indicated that the ?vessel area 1-month post-TRAB was positive correlated
      with IOP 6-month post-TRAB (beta = 3.88, p = 0.042). CONCLUSIONS: Filtering bleb
      vascularization evaluation using OCT-A could potentially predict IOP 6-month post
      TRAB. Surgery effect predicted by filtering bleb vascularization detection is
      conducive to the select specific postoperative intervention to improve the
      success rate of TRAB.

PMID- 30209569
TI  - Single agent efficacy of the HDAC inhibitor DATS in preclinical models of
      glioblastoma.
AB  - PURPOSE/INTRODUCTION: Glioblastoma (GB) remains incurable despite aggressive
      chemotherapy, radiotherapy, and surgical interventions; immunotherapies remain
      experimental in clinical practice. Relevant preclinical models that can
      accurately predict tumor response to therapy are equally challenging. This study
      aimed to validate the effect of the naturally occurring agent diallyl trisulfide
      (DATS) in human GB in relevant pre-clinical models. METHODS: Ex vivo slice
      culture, in vivo cell line derived orthotopic xenograft and patient-derived
      orthotopic xenograft (PDX) animal models of GB were utilized to assess efficacy
      of treatment with DATS. RESULTS: Our results showed 72-h treatments of 25 uM DATS
      induced cell death in ex vivo human GB slice culture. We treated U87MG orthotopic
      xenograft models (U87MGOX) and patient-derived orthotopic xenograft models (PDX)
      with daily intraperitoneal injections of DATS for 14 days. Magnetic resonance
      (MR) imaging of mice treated with DATS (10 mg/kg) demonstrated reduced tumor size
      at 5 weeks when compared with saline-treated U87MGOX and PDX controls.
      Hematoxylin (H&E) staining demonstrated dose-dependent reduction in gross tumor
      volume with decreased proliferation and decreased angiogenesis. Western blotting
      showed that DATS was associated with increases in histone acetylation (Ac-Histone
      H3/H4) and activated caspase-3 in this novel preclinical model. Histological
      assessment and enzyme assays showed that even the highest dose of DATS did not
      negatively impact hepatic function. CONCLUSIONS: DATS may be an effective and
      well-tolerated therapeutic agent in preventing tumor progression and inducing
      apoptosis in human GB.

PMID- 30209571
TI  - The expected oddball: effects of implicit and explicit positional expectation on
      duration perception.
AB  - The oddball duration effect describes how a rare stimulus amongst a string of
      standard stimuli is perceived to have a longer duration than the standards, even
      if they are of the same objective duration. Several theories have been proposed
      to explain this phenomenon. In order to adjudicate between opposing explanations,
      we have borrowed three extensively studied paradigms from the variable foreperiod
      literature: the sequential foreperiod, temporal cueing and a skewed foreperiod
      distribution. This approach allowed us to examine the effects of positional
      expectation on perceived oddball duration, while avoiding confounds from first
      order positioning of the oddball in a sequence of standards. Through these three
      experiments, we demonstrate a clear role of positional expectation in the
      lengthening of the perceived duration of an oddball. We show that this
      expectation effect is separable from other drivers of the oddball duration
      illusion.

PMID- 30209570
TI  - Microbial Communities of the Gut and Nest of the Humus- and Litter-Feeding
      Termite Procornitermes araujoi (Syntermitinae).
AB  - The evolution of the symbiotic association with microbes allowed termites to
      decompose ingested lignocellulose from plant-derived substrates, including
      herbivore dung and soil humus. Representatives of the Syntermitinae (Termitidae)
      range in their feeding habits from wood and litter-feeding to humus-feeding
      species. However, only limited information is available about their feeding
      ecology and associated microbial communities. Here we conducted a study of the
      microbial communities associated to the termite Procornitermes araujoi using
      Illumina sequencing of the 16S and ITS rRNA genes. This species has been
      previously included in different feeding guilds. However, most aspects of its
      feeding ecology are unknown, especially those associated to its symbiotic
      microbiota. Our results showed that the microbial communities of termite guts and
      nest substrates of P. araujoi differed significantly for bacteria and fungi.
      Firmicutes dominated the bacterial gut community of both workers and soldiers,
      whereas Actinobacteria was found in higher prevalence in the nest walls.
      Sordariomycetes was the most abundant fungal class in both gut and nest samples
      and distinguish P. araujoi from the grass/litter feeding Cornitermes cumulans.
      Our results also showed that diversity of gut bacteria were higher in P. araujoi
      and Silvestritermes euamignathus than in the grass/litter feeders (C. cumulans
      and Syntermes dirus), that could indicate an adaptation of the microbial
      community of polyphagous termites to the higher complexity of their diets.

PMID- 30209572
TI  - Reducing Healthcare Costs Using ACS NSQIP-Driven Quality Improvement Projects: A
      Success Story from Sheikh Khalifa Medical City (SKMC).
AB  - INTRODUCTION: Surgical complications increase hospital length of stay and costs
      and lead to poor patient experience. We aim to evaluate our complication rates
      over time and the financial impact of joining the adult multi-specialty American
      College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) at
      Sheikh Khalifa Medical City (SKMC). METHODS: Sheikh Khalifa Medical City is a
      Joint Commission International-accredited ACS NSQIP member since 2009. For the
      purpose of quality improvement, we have established several task forces (2010
      2014) to decrease high rates of venous thromboembolism (VTE), urinary tract
      infection (UTI), surgical site infection (SSI), unplanned intubation (UI), and
      ventilator more than 48 h (Vent > 48 h). Our aim is to evaluate our complication
      rates over time and calculate the cost savings from prevented occurrences in VTE,
      UTI, SSI, UI, and Vent > 48 h. Cost savings are calculated using the return on
      investment calculator from ACS NSQIP. In addition, the cost of joining and
      maintaining ACS NSQIP at SKMC is calculated to determine the total cost savings
      after subtracting these costs. RESULTS: During the study period, we performed
      8842 cases (2009-2015) and our overall morbidity improved significantly from
      observed/expected (O/E) 1.61% to (O/E) 0.85%. We prevented 12 VTE cases (2011
      2015), 56 UTI cases (2013-2015), 12 SSI cases (2013-2015), 4 UI cases (2014
      2015), and 7 Vent > 48 h cases (2014-2015). The cost saving from all these four
      task forces was $1,680,000. The cost of joining and maintaining ACS NSQIP at SKMC
      since 2009 was $336,000. Hence, the total saving for SKMC was $1,344,000.
      CONCLUSION: ACS NSQIP-driven quality improvement projects have resulted in
      reduction in complications and healthcare costs at SKMC over a 6-year period.

PMID- 30209573
TI  - The Unacceptable Morbidity of Negative Laparoscopic Appendicectomy.
AB  - BACKGROUND: One of the most common acute conditions managed by general surgeons
      is acute appendicitis. Laparoscopic appendicectomy (LA) is the surgical technique
      used by many surgeons. The aims of this study were to define our unit's negative
      appendicectomy rate and compare the outcomes associated with removal of a normal
      appendix with those for acute appendicitis in patients having LA. METHODS: A
      single-centre retrospective case note review of patients undergoing LA for
      suspected acute appendicitis was performed. Patients were divided into positive
      and negative appendicectomy groups based on histology results. The positive group
      was subdivided into uncomplicated and complicated (perforated and/or gangrenous)
      appendicitis. Outcomes were compared between groups. RESULTS: There were 1413
      patients who met inclusion criteria, 904 in the positive group and 509 in the
      negative group, an overall negative appendicectomy rate of 36.0%. Morbidity rates
      (6.3% vs. 6.9%; P = 0.48) and types of morbidity were the same for negative
      appendicectomy and uncomplicated appendicitis. There was no significant
      difference in complication severity (all P > 0.17) or length of stay (2.3 vs. 2.6
      days; P = 0.06) between negative appendicectomy and uncomplicated appendicitis
      groups. Patients with complicated appendicitis had a significantly higher
      morbidity rate compared to negative and uncomplicated groups (20.1% vs. 6.3% and
      20.1% vs. 6.9%; both P < 0.001). CONCLUSION: The morbidity of negative LA is the
      same as LA for uncomplicated appendicitis. The morbidity of LA for complicated
      appendicitis is significantly higher. The selection criteria for LA in our unit
      needs to be reviewed to address the high negative appendicectomy rate and avoid
      unnecessary surgery and its associated morbidity.

PMID- 30209574
TI  - Regulation of plant cell wall stiffness by mechanical stress: a mesoscale
      physical model.
AB  - A crucial question in developmental biology is how cell growth is coordinated in
      living tissue to generate complex and reproducible shapes. We address this issue
      here in plants, where stiff extracellular walls prevent cell migration and
      morphogenesis mostly results from growth driven by turgor pressure. How cells
      grow in response to pressure partly depends on the mechanical properties of their
      walls, which are generally heterogeneous, anisotropic and dynamic. The active
      control of these properties is therefore a cornerstone of plant morphogenesis.
      Here, we focus on wall stiffness, which is under the control of both molecular
      and mechanical signaling. Indeed, in plant tissues, the balance between turgor
      and cell wall elasticity generates a tissue-wide stress field. Within cells,
      mechano-sensitive structures, such as cortical microtubules, adapt their behavior
      accordingly and locally influence cell wall remodeling dynamics. To fully
      apprehend the properties of this feedback loop, modeling approaches are
      indispensable. To that end, several modeling tools in the form of virtual tissues
      have been developed. However, these models often relate mechanical stress and
      cell wall stiffness in relatively abstract manners, where the molecular
      specificities of the various actors are not fully captured. In this paper, we
      propose to refine this approach by including parsimonious biochemical and
      biomechanical properties of the main molecular actors involved. Through a coarse
      grained approach and through finite element simulations, we study the role of
      stress-sensing microtubules on organ-scale mechanics.

PMID- 30209575
TI  - Prospective study on metal ceramic crowns in private practice settings: 20-year
      results.
AB  - OBJECTIVES: Posterior metal ceramic crowns are still widely used as a standard
      treatment. The aim of this study was to obtain long-term data on their clinical
      performance. MATERIAL AND METHODS: Ten private practitioners participated in this
      prospective practice-based study. Patients were provided with two crowns each.
      Two groups were formed. The single crown group comprised 95 patients with 190
      crowns. The retainer crown group comprised 138 patients with fixed dental
      prostheses and 276 retainer crowns. RESULTS: For the primary outcome "loss of
      tooth or crown," 20-year survival rates of 78.8% in the single crown group and
      67.8% in the retainer crown group were found. Veneering ceramic defects occurred
      rather frequently, resulting in respective 20-year technical success rates of
      74.2% for single crowns and 62.9% for retainer crowns. However, veneering ceramic
      defects causing crown losses were very rare events. CONCLUSIONS: The results
      contribute to our knowledge on long-term outcomes of treatments with metal
      ceramic crowns and show high survival and success rates over 20 years. CLINICAL
      RELEVANCE: Posterior metal ceramic crowns are a highly reliable option in private
      practice settings.

PMID- 30209576
TI  - Use of propofol for prevention of post-delivery nausea during cesarean section: a
      double-blind, randomized, placebo-controlled trial.
AB  - PURPOSE: Nausea and vomiting are common, undesirable symptoms during cesarean
      section. We conducted this study to assess the antiemetic properties of propofol
      for the prevention and immediate treatment of post-delivery nausea and vomiting
      during cesarean section under combined spinal-epidural anesthesia. METHODS:
      Eighty women undergoing elective cesarean delivery under combined spinal-epidural
      anesthesia were randomized to receive either propofol at a plasma concentration
      of 1000 ng/mL or normal saline immediately after clamping of the umbilical cord.
      The incidence of post-delivery nausea and vomiting, patients requiring rescue
      antiemetic, bispectral index, sedation score, and the incidence of hypotension
      were assessed intraoperatively. Satisfaction and neonatal behavioral neurological
      assessments were evaluated postoperatively. RESULTS: The incidence of nausea was
      significantly lower in the propofol group compared to the placebo group (25%
      versus 60%, P < 0.001). The incidence of retching and vomiting showed no
      significant difference between the two groups. Propofol 20 mg as a rescue
      antiemetic was significantly effective in both the groups. Satisfaction level of
      patients and obstetricians in the propofol group was higher than in the placebo
      group. There was no statistical difference in the incidence of hypotension
      between the two groups both pre- and post-delivery. There was no difference in
      postoperative neonatal behavioral neurological assessment between groups.
      CONCLUSION: Propofol at a plasma concentration of 1000 ng/mL significantly
      reduced the incidence of post-delivery nausea compared to placebo, but had no
      effect on reducing retching or vomiting episodes during cesarean section.

PMID- 30209577
TI  - Perioperative factors associated with aneurysm sac size changes after
      endovascular aneurysm repair.
AB  - PURPOSE: To identify the perioperative factors associated with aneurysm size
      changes after endovascular aortic aneurysm repair (EVAR). METHODS: Between
      August, 2008 and December, 2014, 187 patients underwent EVAR treatment in our
      institution. The subjects of this study were 135 of these patients without
      peripheral artery disease, who were followed up with computed tomography (CT) for
      3 years. Significant aneurysm size change was defined as sac size change of more
      than 5 mm from the baseline. RESULTS: Sac enlargement was identified in 25
      patients (18.5%) and sac shrinkage was identified in 59 (43.7%) patients. The
      factors associated with sac enlargement were postoperative pulse wave velocity
      (OR: odds ratio 3.80, p = 0.047), prevalence of a type 2 endoleak 1 week after
      surgery (OR 4.26, p = 0.022), inner diameter (OR 1.10, p = 0.005), and distance
      from the lower renal artery to the terminal aorta (OR 1.05, p = 0.017). The
      factors associated with sac shrinkage were prevalence of a type 2 endoleak (OR
      0.09, p < 0.001) and preoperative pulse wave velocity (OR 0.32, p = 0.022). The
      factors independently associated with type 2 endoleak were the use of an Excluder
      device (OR 3.99, p = 0.002) and the length of the aneurysm (OR 1.02, p = 0.027).
      CONCLUSION: Inner diameter, treatment length, perioperative pulse wave velocity,
      and type 2 endoleak were associated with sac size changes after EVAR.

PMID- 30209578
TI  - Reactivity of the [Au(C^N^C)Cl] complex in the presence of H2O and N-, S- and Se
      containing nucleophiles: a DFT study.
AB  - Gold complexes are promising compounds used in cancer chemotherapy. Besides their
      steric features, which enable biomolecule interactions, the redox instability and
      the high affinity of gold with cellular nucleophiles influence the biological
      action in these complexes. Both features were herein theoretically investigated
      for the [Au(C^N^C)Cl] probe complex (C^N^C = 2,6-diphenylpyridine) using H2O,
      CH3SH/CH3S-, CH3Se- and meim-4-H (4-methylimidazole) as biomimetic nucleophiles.
      Based on the results, the lowest energy reaction path followed two consecutive
      steps: (1) chloride-exchange ([Formula: see text] = 4.14 * 107 M-1 s-1) and (2)
      reduction of the resulting Au(III) metabolite to the corresponding Au(I) analog
      with chelate ring-opening ([Formula: see text] =+0.15 V-data based on the
      reaction with CH3Se-). These findings bring new insights about the mechanism of
      the Au(III) complex/biomolecule interaction in the cell, which is responsible for
      triggering biological responses.

PMID- 30209579
TI  - A novel thermophilic hemoprotein scaffold for rational design of biocatalysts.
AB  - Hemoproteins are commonly found in nature, and involved in many important
      cellular processes such as oxygen transport, electron transfer, and catalysis.
      Rational design of hemoproteins can not only inspire novel biocatalysts but will
      also lead to a better understanding of structure-function relationships in native
      hemoproteins. Here, the heme nitric oxide/oxygen-binding protein from
      Caldanaerobacter subterraneus subsp. tengcongensis (TtH-NOX) is used as a novel
      scaffold for oxidation biocatalyst design. We show that signaling protein TtH-NOX
      can be reengineered to catalyze H2O2 decomposition and oxidation of 2,2'-azino
      bis(3-ethylbenzothiazoline-6-sulphonic acid) by H2O2. In addition, the role of
      the distal tyrosine (Tyr140) in catalysis is investigated. The mutation of Tyr140
      to alanine hinders the catalysis of the oxidation reactions. On the other hand,
      the mutation of Tyr140 to histidine, which is commonly observed in peroxidases,
      leads to a significant increase of the catalytic activity. Taken together, these
      results show that, while the distal histidine plays an important role in
      hemoprotein reactions with H2O2, it is not always essential for oxidation
      activity. We show that TtH-NOX protein can be used as an alternative scaffold for
      the design of novel biocatalysts with desired reactivity or functionality. H-NOX
      proteins are homologous to the nitric oxide sensor soluble guanylate cyclase.
      Here, we show that the gas sensor protein TtH-NOX shows limited capacity for
      catalysis of redox reactions and it can be used as a novel scaffold in
      biocatalysis design.

PMID- 30209581
TI  - Decreased expression of G-protein-coupled receptors GPR43 and GPR109a in
      psoriatic skin can be restored by topical application of sodium butyrate.
AB  - The G-protein-coupled receptors GPR43 and GPR109a are known to play an important
      role in mediating anti-inflammatory and anti-cancer functions in the gut. Short
      chain fatty acids, such as sodium butyrate (SB), are activators of GPR43 and
      GPR109a and thereby promote anti-inflammatory effects. The present study aimed to
      examine the expression of these receptors and their reaction to SB in psoriasis.
      Lesional and non-lesional biopsies of 6 psoriasis patients and of 4 controls were
      obtained and stained for GPR109a and GPR43. Ex vivo stimulation with SB was
      performed on fresh biopsy material. Lesional and non-lesional psoriatic skin
      showed a decreased expression of GPR109a and GPR43 on keratinocytes in comparison
      with control skin. Topical application of SB was able to increase the low-level
      expression of both receptors. The data suggest that SB by restoring the impaired
      expression of GPR109a and GPR43 might exert anti-inflammatory effects and may be
      utilized as a topical tool for the treatment of psoriasis, which has to be proven
      in future clinical trials.

PMID- 30209580
TI  - The role of TrkA in the promoting wounding-healing effect of CD271 on epidermal
      stem cells.
AB  - CD271, a receptor of nerve growth factor (NGF), affects the biological properties
      of epidermal stem cells (eSCs) which are essential for skin wound closure.
      Tropomyosin-receptor kinase A (TrkA), another receptor of NGF, combined with
      CD271 has been involved with nervous system and skin keratinocytes. However, the
      exact role of TrkA combined with CD271 in eSCs during skin wound closure is still
      unclear. This study aimed to reveal the role of TrkA in the promoting wounding
      healing effect of CD271 on eSCs. We obtained CD271-vo (over-expression of CD271)
      eSCs by lentiviral infection. K252a was used to inhibit TrkA expression. Full
      thickness skin mouse wound closure model (5 mm in diameter) was used to detect
      the ability of CD271 over-expressed/TrkA-deficient during wound healing. The
      biological characteristics of eSCs and their proliferation and apoptosis were
      detected using immunohistochemistry and western blot. The expressions of protein
      kinase B (pAkt)/Akt, phosphorylated extracellular-signal-related kinase
      (pERK)/ERK1/2, and c-Jun N-terminal kinase (pJNK)/JNK were also detected by
      western blot. We found that over-expression of CD271 promoted the biological
      functions of eSCs. Interestingly, over-expression of CD271 in the absence of TrkA
      neither promoted eSCs' migration and proliferation nor promoted wound healing in
      a mouse model. In addition, we observed the reduced expression of pAkt/Akt and
      pERK/ERK1/2 following TrkA inhibition in vitro. Our studies demonstrated that the
      role of TrkA in the promoting wounding-healing effect of CD271 on eSCs.

PMID- 30209582
TI  - Total spondylectomy for Enneking stage III giant cell tumor of the mobile spine.
AB  - PURPOSE: We reported the surgical outcomes of total en bloc spondylectomy (TES)
      with intralesional T-saw transpedicular osteotomy in patients with Enneking stage
      III spinal giant cell tumors (GCTs). METHODS: The medical records and imaging and
      pathological studies of 25 consecutive patients with Enneking stage III spinal
      GCTs undergoing surgery at our institution who were followed for at least 2 years
      were retrospectively reviewed. RESULTS: Eight men and 17 women (mean age: 34.2
      years, range 16-51 years, at the time of surgery) were included. Six patients
      underwent previous tumor excision at another hospital, and one patient had a
      history of denosumab treatment. The GCTs were at the cervical, thoracic, and
      lumbar levels in three, nine, and 13 patients, respectively. TES was performed in
      13 patients; 12 required intralesional pediculotomy. The remaining patients
      underwent total piecemeal spondylectomy with further intralesional tumor
      resection. During a mean follow-up of 99.2 months (range 24-216), two patients
      who underwent total piecemeal spondylectomy had local tumor recurrence, but no
      patients who underwent TES with intralesional pediculotomy had recurrence. The 2-
      and 10-year recurrence-free survival rates of patients treated with total
      piecemeal spondylectomy were 91.7% and 78.6%, respectively, while those of
      patients treated with TES were both 100%. CONCLUSIONS: TES with intralesional
      pediculotomy had a good surgical outcome even in patients with Enneking stage III
      spinal GCT, suggesting that minimal intralesional procedures could radically cure
      spinal GCTs. These slides can be retrieved under Electronic Supplementary
      Material.

PMID- 30209583
TI  - Variety of preoperative MRI changes in spinal cord ependymoma of WHO grade II: a
      case series.
AB  - PURPOSE: To report a case series of surgically proven spinal ependymomas of WHO
      grade II in which there were changes in the preoperative MRI characteristics over
      time. METHODS: A total of 71 patients with spinal cord ependymoma of WHO grade II
      underwent surgery. There were ten cases in which surgery was performed at an
      average of 2.2 years after the tumor was found. Cystic components, syringomyelia,
      hemorrhage "cap sign," Gd enhancement pattern, characteristic changes in MRI, MIB
      1 index, and neurological assessment during the preoperative period were
      examined. RESULTS: Cases with a huge cyst showed further enlargement of the cyst
      on the caudal and rostral sides with hemosiderin formation over time and changes
      in the pattern of Gd enhancement. In contrast, cases without initial cyst did not
      show cyst formation, and nodular homogeneous lesion remained without changes in
      Gd enhancement. Regarding neurological status, two cases with cyst enlargement
      and hemosiderin formation had worsened non-independent gait preoperatively.
      CONCLUSIONS: MRI in cases of spinal ependymomas of WHO grade II showed
      characteristics such as hemorrhage and cyst formation that varied over time. In
      particular, cases with cyst and hemosiderin showed tumor enlargement, including
      enlargement of lesions on the caudal and rostral sides and enlargement of Gd
      enhanced lesions. These characteristics might influence gait ability during
      preoperative period. We emphasize that early surgery is still the standard of
      care for cervical intramedullary ependymoma, and our findings in this study
      should not be interpreted to indicate that such early surgery is not necessary in
      symptomatic cases. These slides can be retrieved under electronic supplementary
      material.

PMID- 30209584
TI  - Complete genome sequence of a novel avian orthoreovirus isolated from gosling,
      China.
AB  - Avian orthoreovirus (ARV) has been considered as a significant pathogen causing
      great infectious diseases to the avian, like broiler and waterfowl. The genome of
      this novel ARV(Reo/SDPY/Goose) was completely sequenced by next-generation
      sequencing. The complete genome was found to be 23517 bp in length with 10
      segments. Although the Reo/SDPY/Goose was isolated from the gosling, it shares
      great similarity, no matter which segment within the genome, with those published
      as avian-origin reovirus. Genomic analysis revealed that this virus was distinct
      from published ARV strains and met criteria to become a novel ARV strain.

PMID- 30209585
TI  - Cellulase-Hemicellulase Activities and Bacterial Community Composition of
      Different Soils from Algerian Ecosystems.
AB  - Soil microorganisms are important mediators of carbon cycling in nature. Although
      cellulose- and hemicellulose-degrading bacteria have been isolated from Algerian
      ecosystems, the information on the composition of soil bacterial communities and
      thus the potential of their members to decompose plant residues is still limited.
      The objective of the present study was to describe and compare the bacterial
      community composition in Algerian soils (crop, forest, garden, and desert) and
      the activity of cellulose- and hemicellulose-degrading enzymes. Bacterial
      communities were characterized by high-throughput 16S amplicon sequencing
      followed by the in silico prediction of their functional potential. The highest
      lignocellulolytic activity was recorded in forest and garden soils whereas
      activities in the agricultural and desert soils were typically low. The bacterial
      phyla Proteobacteria (in particular classes alpha-proteobacteria, delta
      proteobacteria, and gamma-proteobacteria), Firmicutes, and Actinobacteria
      dominated in all soils. Forest and garden soils exhibited higher diversity than
      agricultural and desert soils. Endocellulase activity was elevated in forest and
      garden soils. In silico analysis predicted higher share of genes assigned to
      general metabolism in forest and garden soils compared with agricultural and arid
      soils, particularly in carbohydrate metabolism. The highest potential of
      lignocellulose decomposition was predicted for forest soils, which is in
      agreement with the highest activity of corresponding enzymes.

PMID- 30209586
TI  - Diversity and Tissue Preference of Osmotolerant Bacterial Endophytes Associated
      with Pearl Millet Genotypes Having Differential Drought Susceptibilities.
AB  - Genetic and functional diversity of osmotolerant bacterial endophytes colonizing
      the root, stem, and leaf tissues of pearl millet genotypes differing in their
      drought susceptibility was assessed. Two genotypes of pearl millet, viz., the
      drought tolerant genotype TT-1 and the drought susceptible genotype PPMI-69, were
      used in the present study. Diazotrophs were found to be the predominant
      colonizers, followed by the Gram positive bacteria in most of the tissues of both
      the genotypes. Higher proportion of bacterial endophytes obtained from the
      drought tolerant genotype was found to be osmotolerant. Results of 16S rRNA gene
      ARDRA analysis grouped 50 of the highly osmotolerant isolates into 16 clusters,
      out of which nine clusters had only one isolate each, indicating their
      uniqueness. One cluster had 21 isolates and remaining clusters were represented
      by isolates ranging from two to four. The representative isolates from each
      cluster were identified, and Bacillus was found to be the most prevalent
      osmotolerant genera with many different species. Other endophytic bacteria
      belonged to Pseudomonas sp., Stenotrophomonas sp., and Macrococcus caseolyticus.
      High phylogenetic diversity was observed in the roots of the drought tolerant
      genotype while different tissues of the drought susceptible genotype showed less
      diversity. Isolates of Bacillus axarquiensis were present in all the tissues of
      both the genotypes of pearl millet. However, most of the other endophytic
      bacteria showed tissue/genotype specificity. With the exception of B.
      axarquiensis and B. thuringiensis, rest all the species of Bacillus were found
      colonizing only the drought-tolerant genotype; while M. caseolyticus colonized
      all the tissues of only the drought susceptible genotype. There was high
      incidence of IAA producers and low incidence of ACC deaminase producers among the
      isolates from the root tissues of the drought-tolerant genotype while reverse was
      the case for the drought-susceptible genotype. Thus, host played an important
      role in the selection of endophytes based on both phylogenetic and functional
      traits.

PMID- 30209587
TI  - Captivity-Induced Changes in the Skin Microbial Communities of Hellbenders
      (Cryptobranchus alleganiensis).
AB  - Variation in environmental conditions can result in disparate associations
      between hosts and microbial symbionts. As such, it is imperative to evaluate how
      environmental variables (e.g., habitat quality) can influence host-associated
      microbiome composition. Within wildlife conservation programs, captive conditions
      can negatively influence the establishment and maintenance of "wild-type"
      microbiotas within a host. Alternative microbial communities can result in the
      proliferation of disease among captive stock or upon reintroduction. Hellbenders
      (Cryptobranchus alleganiensis) are a threatened salamander for which extensive
      captive management is currently employed. Using metabarcoding, we characterized
      the skin microbiota of wild and captive hellbenders from two subspecies in the
      state of Missouri, the eastern (C. a. alleganiensis) and the Ozark hellbender (C.
      a. bishopi). Both subspecies in our study included wild adults and captive
      juveniles that were collected from the wild as eggs. Our objectives were to
      investigate differences in the skin microbial communities' richness/diversity,
      composition, and functional profiles of microbes between wild and captive
      individuals. Captive eastern hellbenders possessed richer communities than wild
      cohorts, whereas the opposite pattern was observed within the Ozark subspecies.
      We found significant microbial community structure between wild and captive
      populations of both subspecies. Microbiota structure translated into differences
      in the predicted metagenome of wild and captive individuals as well. As such, we
      can expect captive hellbenders to experience alternative microbial structure and
      function upon reintroduction into the wild. Our study provides a baseline for the
      effect of captivity on the skin microbial communities of hellbenders, and
      highlights the need to incorporate microbiota management in current captive
      rearing programs.

PMID- 30209588
TI  - Mesoporous silica coating NaYF4:Yb,Er@NaYF4 upconversion nanoparticles loaded
      with ruthenium(II) complex nanoparticles: Fluorometric sensing and cellular
      imaging of temperature by upconversion and of oxygen by downconversion.
AB  - Accurate detection of temperature and oxygen concentration at the cellular level
      is important in tumor diagnosis. Multifunctional nanocomposites are described
      that consist of upconversion luminescent nanoparticles capped with mesoporous
      silica and loaded with an oxygen-sensitive luminescent ruthenium complex. The
      nanocomposites of type NaYF4:Yb,Er@NaYF4@mSiO2-Ru have two modes of operation:
      Its red downconversion luminescence (at excitation/emission peaks of 455/606 nm)
      is quenched by oxygen (O2), and this is used to sense and image O2. The green
      upconversion luminescence (typically acquired at excitation/emission wavelengths
      of 980/525 and 544 nm), in turn, is used to measure temperature. The
      nanocomposites were then applied to dual mode in-vitro imaging of temperature and
      O2 in hepatocellular carcinoma cells (HepG-2). Graphical abstract A new
      multifunctional nanocomposite of mesoporous silica coating NaYF4:Yb,Er@NaYF4
      upconversion nanopaticless loaded with ruthenium (II) complex has been designed
      with both green upconversion and red downconversion luminescence for temperature
      detection, oxygen sensing and dual mode cell imaging.

PMID- 30209590
TI  - Correction to: Xenobiotica-metabolizing enzymes in the skin of rat, mouse, pig,
      guinea pig, man, and in human skin models.
AB  - This article is published with the incorrect copyright holder name in the HTML
      article as "(c) Springer 2018". The correct copyright line should read "The
      Author(s) 2018" (as it appears in the article PDF).

PMID- 30209589
TI  - A phase I/randomized phase II study of GM.CD40L vaccine in combination with CCL21
      in patients with advanced lung adenocarcinoma.
AB  - The GM.CD40L vaccine, which recruits and activates dendritic cells, migrates to
      lymph nodes, activating T cells and leading to systemic tumor cell killing. When
      combined with the CCL21 chemokine, which recruits T cells and enhances T-cell
      responses, additive effects have been demonstrated in non-small cell lung cancer
      mouse models. Here, we compared GM.CD40L versus GM.CD40L plus CCL21
      (GM.CD40L.CCL21) in lung adenocarcinoma patients with >= 1 line of treatment. In
      this phase I/II randomized trial (NCT01433172), patients received intradermal
      vaccines every 14 days (3 doses) and then monthly (3 doses). A two-stage minimax
      design was used. During phase I, no dose-limiting toxicities were shown in three
      patients who received GM.CD40L.CCL21. During phase II, of evaluable patients,
      5/33 patients (15.2%) randomized for GM.DCD40L (p = .023) and 3/32 patients
      (9.4%) randomized for GM.DCD40L.CCL21 (p = .20) showed 6-month progression-free
      survival. Median overall survival was 9.3 versus 9.5 months with GM.DCD40L versus
      GM.DCD40L.CCL21 (95% CI 0.70-2.25; p = .44). For GM.CD40L versus GM.CD40L.CCL21,
      the most common treatment-related adverse events (TRAEs) were grade 1/2 injection
      site reaction (51.4% versus 61.1%) and grade 1/2 fatigue (35.1% versus 47.2%).
      Grade 1 immune-mediated TRAEs were isolated to skin. No patients showed evidence
      of pseudo-progression or immune-related TRAEs of grade 1 or greater of
      pneumonitis, endocrinopathy, or colitis, and none discontinued treatment due to
      toxicity. Although we found no significant associations between vaccine
      immunogenicity and outcomes, in limited biopsies, one patient treated with
      GMCD40L.CCL21 displayed abundant tumor-infiltrating lymphocytes. This possible
      effectiveness warrants further investigation of GM.CD40L in combination
      approaches.

PMID- 30209592
TI  - Development and validation of an ultrasound-based nomogram to improve the
      diagnostic accuracy for malignant thyroid nodules.
AB  - OBJECTIVES: The aim of this study was to develop an ultrasound-based nomogram to
      improve the diagnostic accuracy of the identification of malignant thyroid
      nodules. METHODS: A total of 1675 histologically proven thyroid nodules (1169
      benign, 506 malignant) were included in this study. The nodules were grouped into
      the training dataset (n = 700), internal validation dataset (n = 479), or
      external validation dataset (n = 496). The grayscale ultrasound features included
      the nodule size, shape, aspect ratio, echogenicity, margins, and calcification
      pattern. We applied least absolute shrinkage and selection operator (lasso)
      regression to select the strongest features for the nomogram. Nomogram
      discrimination (area under the receiver operating characteristic curve, AUC) and
      calibration were assessed. The nomogram was subjected to bootstrapping validation
      (1000 bootstrap resamples) to calculate a mean AUC and 95% confidence interval
      (CI). RESULTS: The nomogram showed good discrimination in the training dataset,
      with an AUC of 0.936 (95% CI: 0.918-0.953) and good calibration. Application of
      the nomogram to the internal validation dataset also resulted in good
      discrimination (AUC: 0.935; 95% CI, 0.915-0.954) and good calibration. The model
      tested in an external validation dataset demonstrated a lower AUC of 0.782 (95%
      CI: 0.776-0.789). CONCLUSIONS: This ultrasound-based nomogram can be used to
      quantify the probability of malignant thyroid nodules. KEY POINTS: * Ultrasound
      examination is helpful in the differential diagnosis of malignant and benign
      thyroid nodules. * However, ultrasound accuracy relies heavily on examiner
      experience. * A less subjective diagnostic model is desired, and the developed
      nomogram for thyroid nodules showed good discrimination and good calibration.

PMID- 30209591
TI  - Comparison of full-iodine conventional CT and half-iodine virtual monochromatic
      imaging: advantages and disadvantages.
AB  - PURPOSE: To compare image quality of abdominal arteries between full-iodine-dose
      conventional CT and half-iodine-dose virtual monochromatic imaging (VMI).
      MATERIALS AND METHODS: We retrospectively evaluated images of 21 patients (10
      men, 11 women; mean age, 73.9 years) who underwent both full-iodine (600 mg/kg)
      conventional CT and half-iodine (300 mg/kg) VMI. For each patient, we measured
      and compared CT attenuation and the contrast-to-noise ratio (CNR) of the aorta,
      celiac artery, and superior mesenteric artery (SMA). We also compared CT dose
      index (CTDI). Two board-certified diagnostic radiologists evaluated visualisation
      of the main trunks and branches of the celiac artery and SMA in maximum-intensity
      projection images. We evaluated spatial resolution of the two scans using an
      acrylic phantom. RESULTS: The two scans demonstrated no significant difference in
      CT attenuation of the aorta, celiac artery, and SMA, but CNRs of the aorta and
      celiac artery were significantly higher in VMI (p = 0.011 and 0.030,
      respectively). CTDI was significantly higher in VMI (p = 0.024). There was no
      significant difference in visualisation of the main trunk of the celiac artery
      and SMA, but visualisation of the gastroduodenal artery, pancreatic arcade,
      branch of the SMA, marginal arteries, and vasa recta was significantly better in
      the conventional scan (p < 0.001). The calculated modular transfer function (MTF)
      suggested decreased spatial resolution of the half-iodine VMI. CONCLUSION: Large
      vessel depiction and CNRs were comparable between full-iodine conventional CT and
      half-iodine VMI images, but VMI did not permit clear visualisation of small
      arteries and required a larger radiation dose. KEY POINTS: ?Reducing the dose of
      iodine contrast medium is essential for chronic kidney disease patients to
      prevent contrast-induced nephropathy. ?In virtual monochromatic images at low
      keV, contrast of relatively large vessels is maintained even with reduced iodine
      load, but visibility of small vessels is impaired with decreased spatial
      resolution. ?We should be aware about the advantages and disadvantages associated
      with virtual monochromatic imaging with reduced iodine dose.

PMID- 30209593
TI  - C-Arm computed tomography (CACT)-guided balloon pulmonary angioplasty (BPA):
      Evaluation of patient safety and peri- and post-procedural complications.
AB  - AIM: To assess the frequency and severity of complications of balloon pulmonary
      angioplasty (BPA) using C-arm computed tomography (CACT) guidance. MATERIAL AND
      METHODS: 266 consecutive interventions in 67 patients (42 females, mean age 66 +/
      13 years) were included. Selective CACT was acquired prior to the intervention
      for three-dimensional (3D) guidance and to select appropriate balloon size based
      on the measured vessel diameter. Complications during and after the procedure,
      the need for further interventions and the impact on patient safety and outcome
      were assessed and categorised according to the SIR Classification System to
      Complications by Outcome (Grade A-F). RESULTS: Overall, 237 interventions were
      conducted without any complications (89.1%). Minor complications not requiring
      additional treatment occurred during or after 25 procedures (9.4%), including
      recurring dry cough in four patients during a total of 11 interventions (4.1%)
      (Grade A), three focal dissections of the targeted pulmonary artery (1.1%), four
      cases of pulmonary haemorrhage (1.5%), one case of reperfusion oedema (0.4%) and
      six cases of post-interventional short-term hemoptysis (2.3%) (Grade B). Four
      cases of major complications requiring additional treatment were observed (1.5%):
      one case of pulmonary haemorrhage (0.4%) and two cases of post-interventional
      haemoptysis (0.8%), all resolved after medical therapy without requiring further
      intervention, and one case of atrial tachycardia induced during catheterisation,
      subsequently requiring pharmacological cardioversion (0.4%) (Grade C). No fatal
      or life-threatening peri- or post-interventional complications or mortality were
      observed (Grade D-F). CONCLUSION: BPA performed under CACT guidance appears to be
      a safe procedure with a low risk of severe complications. KEY POINTS: * CACT
      guidance of BPA is safe and successful. * CACT-guided BPA procedures have a low
      complication profile. * CACT guidance is a valuable tool to navigate BPA.

PMID- 30209595
TI  - [Oxycodone, piritramide and tramadol for the management of postoperative pain : A
      registry study on use and effectiveness in clinical routine].
AB  - BACKGROUND: In the context of improving perioperative pain management and
      shortening hospital stays, potent oral analgesics, such as slow release opioids,
      are gaining increasingly in importance. OBJECTIVE: The aim of this study was to
      compare the use and effectiveness of different opioids in postoperative pain
      treatment in Germany. MATERIALS AND METHODS: Using data from the QUIPS database,
      the records of 5249 patients were evaluated. The total study population was
      divided into four groups: group 1 (10 mg oxycodone with or without naloxone 5
      mg), group 2 (20 mg oxycodone with or without naloxone 10 mg), group 3
      (piritramide) and group 4 (tramadol). Maximum pain intensity, pain-related
      interference with sleep and respiration, vomiting, postoperative fatigue, desire
      for more pain treatment and satisfaction with pain management were evaluated.
      RESULTS AND DISCUSSION: The differences in pain intensity were statistically
      significant between groups. Patients with piritramide reported more pain, more
      interference with sleep and respiration and more fatigue compared to those from
      the other groups. In the group with 10 mg oxycodone, the desire for additional
      pain medication was the lowest. Postoperative vomiting and satisfaction with pain
      management differed significantly between the four groups. Procedure-specific
      analysis has shown that differences between sub-groups were also significant
      following cholecystectomy and total knee arthroplasty. CONCLUSIONS: In summary,
      our findings suggest that postoperative pain treatment with slow release oral
      oxycodone does not show disadvantages compared to tramadol or piritramide with
      regard to pain-related impairments and opioid-induced side effects. This
      hypothesis needs to be further analyzed in controlled studies.

PMID- 30209596
TI  - Peripheral nerve injuries in the pediatric population: a review of the
      literature. Part II: entrapment neuropathies.
AB  - INTRODUCTION: Entrapment neuropathies are infrequent in children, and therefore
      remain unrecognized. The incidence of radial, median, and cubital
      mononeuropathies are all similar. Despite the rarity of such cases, extensive,
      albeit scattered, literature has accumulated concerning entrapment neuropathies
      in children. OBJECTIVE: To the literature concerning entrapment neuropathies in
      children. METHODS: A systematic review of the existing literature has been made.
      RESULTS: The management of chronic pediatric pain is very important in such
      patients to prevent youths from experiencing prolonged absences from school,
      sports, or other productive activities, and limit the psychological burden of
      chronic disease. Nonsurgical treatment of both cubital and carpal tunnel
      syndromes has been disappointing in pediatric patients, with only limited
      success; and, to date, there is no clear explanation for the outcome differences
      generated by nonsurgical management between adults and youths. Simple
      decompression of the ulnar nerve at the elbow also has much higher rates of
      failure in children than in adults. CONCLUSIONS: The presence of an entrapment
      neuropathy (specially carpal tunnel syndrome) in a pediatric-age patient should
      alert medical care providers to the potential of some underlying genetic
      condition or syndrome.

PMID- 30209594
TI  - A long-term follow-up in conservative management of unilateral ureteropelvic
      junction obstruction with poor drainage and good renal function.
AB  - : The aim of the study was to retrospectively review the outcome of neonatal
      ureteropelvic junction obstruction with a good renal function and a poor drainage
      at a first diuretic renal scan, in cases where surgery was recommended on the
      basis of a loss of renal function, worsening of hydronephrosis or occurrence of
      clinical symptoms. Hydronephrosis was graded from 1 to 4 or as ureteral tract
      dilatation (UTD) P1 to UTD P3. During follow-up, 15 out of 38 patients (34.2%)
      required surgery while 25 out of 38 (65.8%) could have been managed
      conservatively. In patients with grade 2, 3, and 4 hydronephrosis, the
      ureteropelvic junction obstruction resolved or improved spontaneously in 100%,
      63%, and 33% of cases (in 100% of UTD P1, 67% of UTD P2, and 50% of UTD P3),
      respectively. The median of follow-up was 14 years. Chi-square test showed a
      significant relationship between initial grade of hydronephrosis or UTD and the
      possibility of an efficient conservative management (p = 0.0088 and p = 0.0460).
      CONCLUSION: Conservative management can be safely achieved in ureteropelvic
      junction obstruction with poor drainage. Scheduled controls are needed for early
      discovery of functional renal deterioration. High-grade hydronephrosis is
      unlikely to resolve spontaneously and is often accompanied by a loss of renal
      function during the first years of life. What is Known: * There is controversy
      about which management should be adopted in infants with unilateral ureteropelvic
      junction obstruction with poor drainage but good differential renal function.
      What is New: * Long-term follow-up suggests that conservative management can be
      safely achieved also in unilateral ureteropelvic junction obstruction with poor
      drainage in more than 60% of cases, even if high-grade hydronephrosis is unlikely
      to resolve spontaneously and it is often accompanied by a loss of renal function
      during the first years of life. In our experience, surgical intervention was
      required in more than 50% of cases before 1 year of life and in all cases before
      3 years of life.

PMID- 30209597
TI  - Alterations in cerebral ventricle size in children with congenital heart disease.
AB  - PURPOSE: Children with tetralogy of Fallot (TOF) and superior cavopulmonary
      anastomoses (SCPA) can have chronically elevated central venous pressure (CVP),
      which has been postulated to put patients at risk for cerebral ventriculomegaly.
      We aimed to examine cerebral ventricle size in children with these congenital
      heart lesions before and after surgery to determine how changes in CVP affect
      ventricle size. METHODS: We reviewed the records of patients who underwent SCPA
      or TOF repair between 2006 and 2015. Patients with pre- or post-operative cranial
      imaging were included. Frontal-occipital (FO) horn ratios were calculated as
      measures of cerebral ventricle volume. Reported normal mean FO ratio is 0.37 +/-
      0.03. Patient characteristics including occipito-fronto circumference (OFC) and
      available CVP measurements were recorded. CVP, FO ratios, and OFC percentiles
      were compared using paired and unpaired t tests and Wilcoxon matched pairs signed
      rank test as appropriate. RESULTS: We reviewed 44 patients who underwent SCPA and
      31 patients who underwent TOF repair who had cranial imaging studies available.
      In the 22 patients who underwent SCPA and had pre- and post-operative imaging,
      mean FO ratios significantly increased from 0.37 +/- 0.03 to 0.40 +/- 0.04 (P <
      0.001). In contrast, in the seven patients with TOF with pre- and post-operative
      imaging, FO ratio was elevated at baseline and remains so after surgical repair,
      0.43 +/- 0.08 to 0.42 +/- 0.08 (P = 0.65). Similar patterns were noted with OFC
      percentiles, which were significantly increased as compared to baseline after
      SCPA (P < 0.001) but were not significantly changed after TOF repair (P = 0.58).
      Finally, when available, preoperative and postoperative CVP measurements of all
      patients were examined, CVP increased in patients who underwent SCPA, from 6.5 +/
      2 mmHg preoperatively to 9.1 +/- 2.3 mmHg postoperatively (P < 0.001), while CVP
      remained statistically unchanged in patients who underwent TOF repair, 12.9 +/-
      3.3 mmHg preoperatively to 14.4 +/- 3.1 mmHg postoperatively (P = 0.2).
      CONCLUSION: Cerebral ventriculomegaly was observed in patients with SCPA and TOF,
      and the observed changes in FO ratio and OFC may be related, at least in part, to
      CVP.

PMID- 30209598
TI  - Grisel's syndrome caused by Mycoplasma pneumoniae infection: a case report and
      review of the literature.
AB  - BACKGROUND: Grisel's syndrome is a non-traumatic subluxation of the atlantoaxial
      joints, which is caused by an inflammatory process involving the upper neck.
      Torticollis, neck pain, and reduced neck mobility are the main clinical signs of
      presentation. Predisposing factors are trauma, hyperlaxity of the transverse and
      alar ligaments of the atlantoaxial joints, and surgical interventions carried out
      in this area. Several viral and bacterial pathogens have been reported as
      causative events of Grisel's syndrome, including Epstein-Barr virus, Kawasaki
      disease, Streptococcus pyogenes, Staphylococcus aureus, and other infectious
      agents. Grisel's syndrome linked to Mycoplasma pneumoniae infection as the
      trigger has not previously been reported. Mycoplasma pneumoniae is a small
      prokaryotic microbe and a frequent etiologic factor of respiratory tract
      infections and, less frequently, of extrapulmonary body organs. The recognition
      of the Grisel's syndrome is based on clinical and neuroradiological
      investigations, and early diagnosis and specific treatment are crucial to the
      successful outcome of the disease. RESULTS: We report the case of an 8-year-old
      girl with Grisel's syndrome caused by an upper respiratory tract infection due to
      Mycoplasma pneumoniae. Diagnostic suspicion and treatment of Grisel's syndrome
      were established quickly by anamnestic and clinical data and confirmed by
      radiological findings. The girl was immediately treated with specific antibiotic
      therapy and cervical immobilization, thus preventing the most dangerous
      complications of the disorder. CONCLUSION: Mycoplasma pneumoniae, among the other
      infectious agents, may be cause of scute torticollis and Gresel's syndrome.

PMID- 30209600
TI  - Do cancer patients use the term resilience? A systematic review of qualitative
      studies.
AB  - PURPOSE: Resilience is a dynamic process of positive adaptation to adversity,
      including cancer. While the term is used frequently by researchers, controversy
      exists over its conceptualisation and little is known if and how cancer patients
      use the term resilience. We examined qualitative studies exploring cancer patient
      experiences/perceptions of resilience to understand: (a) definitions of
      resilience as identified by patients and researchers and (b) the themes relating
      to attributes of resilience as identified by patients. METHODS: Four electronic
      databases (MEDLINE, PsycINFO, SCOPUS, and CINAHL) were searched from database
      inception to November 2017, identifying qualitative studies of adult cancer
      patients/survivors which included resilience and cancer in the title, abstract,
      or medical subject headings. Articles were excluded if resilience was not a theme
      or outcome or was discussed primarily in the context of non-individuals. Thematic
      analysis was used to code studies and generate analytical themes, and a single
      author identified definitions of resilience within the studies. RESULTS: Five
      hundred and seventy-three non-duplicate citations were screened, resulting in 65
      citations screened for full-text review. Of these, 33 were excluded, leaving 32
      studies. Four thematic categories emerged; coping strategies, social support,
      spirituality, and growth, within which 79 individual themes were identified.
      Eight researcher definitions and no patient definitions of resilience were
      identified. CONCLUSION: This review found no cancer patient definitions of
      resilience and that cancer patients are seldom quoted using the term resilience
      directly, instead identifying coping strategies, social support, growth, and
      spirituality as attributes associated with resilience.

PMID- 30209599
TI  - Is arachnoid cyst a static disease? A case report and literature review.
AB  - INTRODUCTION: The increasing use of intracranial imaging has led to more frequent
      diagnoses of arachnoid cysts (ACs). Although ACs are a frequent finding on
      neuroimaging in children, the prevalence and natural history of these cysts are
      not well defined. Most ACs may persist and remain asymptomatic throughout life
      and not require treatment. However, there have been some case reports of ACs that
      have become larger or smaller over time and, in rare cases, have even
      spontaneously resolved. It is the authors' practice to recommend serial
      neuroimaging in patients with asymptomatic sylvian ACs and not offer surgery to
      patients without symptoms, even in those with a relatively large cyst. CASE
      REPORT: The present article describes a case involving a 6-year-old boy with a
      large, asymptomatic AC in the left Sylvian fissure involving the temporo-frontal
      region, which resolved spontaneously during the 2-year follow-up period after
      initial diagnosis without any surgical intervention. Currently, at the 7-year
      follow-up, the patient has remained neurologically intact, attends school, and is
      symptom-free. CONCLUSION: Clinicians should be mindful of the possibility of
      spontaneous regression when encountering patients with asymptomatic and/or
      incidentally diagnosed sylvian ACs.

PMID- 30209601
TI  - The earlier the better: the role of palliative care consultation on aggressive
      end of life care, hospice utilization, and advance care planning documentation
      among gynecologic oncology patients.
AB  - PURPOSE: To evaluate the role of specialty palliative care consultation (PCC) on
      end of life care outcomes among terminally ill gynecologic oncology patients.
      METHODS: Retrospective chart review of currently deceased gynecologic oncology
      patients seen at a single, academic institution between October 2006 and October
      2016. Clinical characteristics and outcomes were examined using descriptive
      statistics and logistic regression. RESULTS: Two hundred and four patients were
      eligible. Forty-one percent underwent at least one marker of aggressive care at
      the end of life. Most (53%) had a PCC prior to death, and of these most were
      inpatient (89%). Patients with a PCC had higher odds of hospice enrollment before
      death (OR 2.55, p = 0.016) and higher odds of advance care planning documentation
      before death (OR 6.79, p = < 0.001). Among patients with an inpatient PCC, 44%
      underwent a marker of aggressive medical care at the end of life and 82% enrolled
      in hospice before death. Among patients with an outpatient PCC, 25% underwent a
      marker of aggressive medical care at the end of life and 92% enrolled in hospice
      before death. Patients with outpatient PCC were engaged in palliative care longer
      than patients with inpatient PCC (median 106 days vs. 33 days prior to death).
      CONCLUSIONS: PCC increased hospice enrollment and advance care planning
      documentation. Patients with outpatient PCC had lower rates of aggressive medical
      care and higher rates of hospice enrollment when compared to inpatient PCC.
      Location of initial PCC plays an important role in end of life care outcomes.

PMID- 30209602
TI  - Social consequences of advanced cancer in patients and their informal caregivers:
      a qualitative study.
AB  - PURPOSE: Cancer threatens the social well-being of patients and their informal
      caregivers. Social life is even more profoundly affected in advanced diseases,
      but research on social consequences of advanced cancer is scarce. This study aims
      to explore social consequences of advanced cancer as experienced by patients and
      their informal caregivers. METHODS: Seven focus groups and seven in-depth semi
      structured interviews with patients (n = 18) suffering from advanced cancer and
      their informal caregivers (n = 15) were conducted. Audiotapes were transcribed
      verbatim and open coded using a thematic analysis approach. RESULTS: Social
      consequences were categorized in three themes: "social engagement," "social
      identity," and "social network." Regarding social engagement, patients and
      informal caregivers said that they strive for normality by continuing their life
      as prior to the diagnosis, but experienced barriers in doing so. Regarding social
      identity, patients and informal caregivers reported feelings of social isolation.
      The social network became more transparent, and the value of social relations had
      increased since the diagnosis. Many experienced positive and negative shifts in
      the quantity and quality of their social relations. CONCLUSIONS: Social
      consequences of advanced cancer are substantial. There appears to be a great risk
      of social isolation in which responses from social relations play an important
      role. Empowering patients and informal caregivers to discuss their experienced
      social consequences is beneficial. Creating awareness among healthcare
      professionals is essential as they provide social support and anticipate on
      social problems. Finally, educating social relations regarding the impact of
      advanced cancer and effective support methods may empower social support systems
      and reduce feelings of isolation.

PMID- 30209603
TI  - A kinetic model of carnosine synthesis in human skeletal muscle.
AB  - Drawing on previously published data, a mathematical model is proposed to
      describe the synthesis of carnosine in muscle using a slow release beta-alanine
      supplement (SR-CarnoSyn(r)). The model pre-supposes that the rate of synthesis
      for any given dose of beta-alanine (within the range 1.6-6.4 g day-1) is constant
      with time, but is first order with respect to daily beta-alanine dose.
      Simultaneously with synthesis, decay in carnosine is also assumed to be
      occurring, the rate in this case being a function of the concentration of
      carnosine. Decay in carnosine appears describable by first-order kinetics. By
      integration of the two rate reactions, a single mathematical equation was derived
      to describe the synthesis of carnosine and which closely fitted the experimental
      data over 56 days. The model, if validated by additional studies, could be used
      to compliment empirical observations of the changes in carnosine in muscle with
      supplementation, and allow objective examination of a number of possible
      influences affecting the rate constants of synthesis and decay.

PMID- 30209604
TI  - Strategies for surgical remediation of the multi-fundoplication failure patient.
AB  - BACKGROUND: Outcomes are not well studied in patients undergoing remediation for
      multi-fundoplication failure, that is, two or more prior failed fundoplications.
      Re-operation must balance reflux control and restoration of the ability to eat
      with the challenge of reconstructing a distorted hiatus and GE junction. The
      purpose of this study is to present our experience with surgical remediation for
      multi-fundoplication failure. METHODS: Medical records were retrospectively
      reviewed of 91 patients who underwent third time or more esophagogastric
      operation for fundoplication failure at a single institution from 2007 to 2016.
      Dysphagia was present in 56% and heartburn in 51%. Median number of prior
      operations was 2 with range up to 6. Anatomic failure consisted of slipped wrap
      in 26 cases, wrap herniation in 23, hiatal stenosis in 24, hiatal mesh
      complication in 8, and wrap dehiscence in 10. Operative approaches generally
      followed an institutional algorithm and consisted of hiatal hernia repair with:
      re-do fundoplication in 55%, takedown of fundoplication alone in 24%, Roux-en-Y
      gastrojejunostomy in 14%, and GE junction resection in 7%. Laparoscopic approach
      was successful in 81%. RESULTS: Mean duration of operations was 217 min and
      median length of stay was 3 days. The complication rate was 13%, with 7%
      undergoing unplanned early re-operation. Patients were followed for mean 11
      months, and recurrent hiatal hernia was detected in 13%. Late re-operation was
      performed in 6% for recurrent hiatal hernia. Recurrent reflux symptomatology
      resolved in 93%. Dysphagia resolved in 84%. There were no significant differences
      in outcomes with regard to number of prior operations, operative approach, BMI,
      or age. CONCLUSIONS: There is no single best approach to remediation in the multi
      fundoplication failure patient. Re-do fundoplication is appropriate in over half
      of patients. Reoperation for multi-fundoplication failure can be performed via
      minimally invasive approach with excellent remediation of symptoms, low
      morbidity, and low recurrence rates.

PMID- 30209605
TI  - Impaired activity of daily living is a risk factor for high medical cost in
      patients of non-variceal upper gastrointestinal bleeding.
AB  - BACKGROUND: Non-variceal upper gastrointestinal bleeding (NVUGIB) is still a
      common and life-threatening disease, thus it would have a big impact on medical
      care cost. However, little is known about risk factors for increased medical care
      cost in NVUGIB patients. AIM: The purpose of the study was to clarify predictor
      of requiring high medical care cost in NVUGIB patients. Patients who underwent
      endoscopic hemostasis due to NVUGIB between April 2012 and March 2015 were
      included in this retrospective study. We analyzed the association between
      patients' background including activity of daily livings (ADL) and high medical
      care cost using logistic regression model. Medical care cost was calculated in
      reference to the "Diagnosis Procedure Combination" which is diagnosis-dominant
      case-mix system in Japan. The cutoff value of high medical care cost was defined
      as its first quartile. ADL was assessed according to Katz-6 score. We defined
      impaired ADL patient who revealed Katz-6 score more than 1. RESULTS: A total of
      128 consecutive patients were included in this study. Median medical care cost
      was 5323 USD (IQR 3661-8172 USD). There were 13 patients (10%) in impaired ADL
      group. In univariate analysis, age and impaired ADL before admission revealed
      significant association with high cost. Of these, impaired ADL was an only
      independent risk factor [odds ratio 15.3 (95% CI 2.49-183)] in multivariate
      analysis. CONCLUSION: Impairment in ADL before admission was an independent
      predictor for high medical care cost with NVUGIB patients.

PMID- 30209606
TI  - Comparison between conventional colectomy and complete mesocolic excision for
      colon cancer: a systematic review and pooled analysis : A review of CME versus
      conventional colectomies.
AB  - BACKGROUND: Complete mesocolic excision (CME) is advocated based on oncologic
      superiority, but not commonly performed in North America. Many data are case
      series with few comparative studies. Our aim was to perform a systematic review
      comparing outcomes between CME and non-CME colectomy. METHODS: A systematic
      review was performed according to PRISMA guidelines of MEDLINE, EMBASE,
      HealthStar, Web of Science, and Cochrane Library. Studies were included if they
      compared conventional resection (non-CME) to CME for colon cancer. Quality was
      assessed using methodological index for non-randomized studies (MINORS). The main
      outcome measures were short-term morbidity and oncologic outcomes. Weighted
      pooled means and proportions with 95% CI were calculated using a random-effects
      model when appropriate. RESULTS: Out of 825 unique citations, 23 studies
      underwent full-text reviews and 14 met inclusion criteria. Mean MINORS score was
      13.3 (range 11-15). The mean sample size in CME group was 1166 (range 45-3756)
      and 945 (range 40-3425) in non-CME. Four papers reported plane of dissection,
      with CME plane achieved in 85.8% (95% CI 79.8-91.7). Mean OR time in CME group
      was 167 min (163-171) and 138 min (135-142) in conventional group. Perioperative
      morbidity was reported in six studies, with pooled overall complications of 22.5%
      (95% CI 18.4-26.6) for CME and 19.6 (95% CI 13.6-25.5) for non-CME. Anastomotic
      leak occurred in 6.0% (95% CI 2.2-9.7) of CME resections versus 6.0% (95% CI 4.1
      7.9) in non-CME. CME had more lymph nodes, longer distance to high tie, and
      specimen length in all studies. Nine studies compared long-term oncologic
      outcomes and only three reported statistically significant higher disease-free or
      overall survival in favor of CME. Local recurrence was lower after CME in two of
      four studies. CONCLUSIONS: The quality of evidence is limited and does not
      consistently support the superiority of CME. Better data are needed before CME
      can be recommended as the standard of care for colon cancer resections.

PMID- 30209607
TI  - Does rating with a checklist improve the effect of E-learning for cognitive and
      practical skills in bariatric surgery? A rater-blinded, randomized-controlled
      trial.
AB  - BACKGROUND: Mental training of laparoscopic procedures with E-learning has been
      shown to translate to the operating room. The present study aims to explore
      whether the use of checklists during E-learning improves transfer of skills to
      the simulated OR on a Virtual Reality (VR) trainer for Roux-en-Y gastric bypass
      (RYGB). METHODS: Laparoscopy naive medical students (n = 80) were randomized in
      two groups. After an E-learning introduction to RYGB, checklist group rated RYGB
      videos using the validated Bariatric Objective Structured Assessment of Technical
      Skills (BOSATS) checklist while group without checklist only observed the videos.
      Participants then performed RYGB on a VR-trainer twice and were evaluated by a
      blinded expert rater using BOSATS. A multiple choice (MC) knowledge test on RYGB
      was performed. Suturing on a cadaveric porcine small bowel was evaluated using
      objective structured assessment of technical skill (OSATS). RESULTS: Checklist
      group was better in the knowledge test (A 8.3 +/- 1.1 vs. B 7.1 +/- 1.3; p <=
      0.001) and there was a trend towards better VR RYGB performance (BOSATS) on the
      first try (85.9 +/- 10.2 vs. 81.1 +/- 11.5; p = 0.058), but not on the second try
      (92.0 +/- 9.7 vs. 89.3 +/- 10.5; p = 0.251). Suturing as measured by OSATS was
      not different (29.5 +/- 3.0 vs. 29.0 +/- 3.5; p = 0.472). CONCLUSION: This study
      presents evidence that the use of a BOSATS checklist during E-learning helps
      trainees to improve their knowledge acquisition with E-learning. The transfer
      from mental training to the simulated OR environment seems to be partially
      enhanced by use of the BOSATS checklist. However, more research is required to
      investigate potential benefits.

PMID- 30209608
TI  - Laparoscopy in penetrating abdominal trauma is a safe and effective alternative
      to laparotomy.
AB  - INTRODUCTION: Diagnostic laparoscopy (DL) is an increasingly used modality when
      approaching penetrating abdominal trauma (PAT). Trauma surgeons can utilize this
      minimally invasive technique to quickly assess for injury in hemodynamically
      stable patients. DL with a confirmed injury can be repaired through therapeutic
      laparoscopy (TL) or conversion to exploratory laparotomy (EL). This study
      analyzes the use of laparoscopy as a first-line therapy for hemodynamically
      stable patients with PAT. METHODS: Data were reviewed of patients presenting with
      PAT between December 2006 and September 2016. A retrospective analysis was
      conducted to analyze demographics, baseline presentations, treatment protocols
      and outcomes. RESULTS: A total of 56 patients with PAT were initially treated
      with laparoscopy. Injuries included stab wounds (n = 48) and gunshot wounds (n =
      8). Patients were divided into three groups: DL, DL to TL, and DL to EL. Ten
      patients (17.9%) required conversion to laparotomy (DL to EL). Of the 46 patients
      who did not require conversion, 33 patients (71.7%) underwent DL, while 13
      patients (28.3%) required TL (DL to TL). There were no differences in
      postoperative complication rates between the groups (p = 0.565). The mean lengths
      of hospital stay for DL, DL to TL, and DL to EL were 3.1, 2.7, and 8.1 days,
      respectively (p = 0.038). No missed injuries or mortalities occurred in any of
      the groups. CONCLUSION: Laparoscopy can be utilized for hemodynamically stable
      patients with PAT. DL can be converted to TL in the hands of a skilled
      laparoscopist. In this study, we analyze the use of DL over a 10-year period in
      patients who presented to our level 1 trauma center with PAT. We also provide a
      comprehensive review of literature to create clear definitions, and to clarify a
      systematic stepwise approach of how to effectively perform DL and TL. This study
      adds to the body of literature supporting the role of laparoscopy in PAT, and
      advances the discussion regarding management.

PMID- 30209609
TI  - Is hyperkinetic gallbladder an indication for cholecystectomy?
AB  - BACKGROUND: The (99m) technetium-labelled hepato imino diacetic acid (HIDA) scan
      is widely used to evaluate patients with biliary colic with a normal trans
      abdominal ultrasound scan. Most studies recommend cholecystectomy for patients
      with biliary dyskinesia, defined by gallbladder ejection fraction (GBEF) of less
      than 35-40% on HIDA scan. There are no recommendations regarding management of
      hyperkinetic gallbladder defined by GBEF of greater than 80% on HIDA scan. The
      aim of our study was to evaluate the outcomes following cholecystectomy on
      patients with biliary colic associated with hyperkinetic gallbladder. METHODS: We
      performed a retrospective chart review of all patients with biliary colic
      associated with hyperkinetic gallbladder that underwent cholecystectomy in our
      practice from July 2014 to February 2018. Data collection included age, gender,
      body mass index, preoperative symptoms, comorbidities, additional tests, ejection
      fraction, surgery, and histopathology of the gallbladder. Symptomatic improvement
      was assessed during routine 2-week postoperative visit and a follow-up phone
      interview. RESULTS: Thirty-two patients had undergone laparoscopic
      cholecystectomy during the study period for symptomatic hyperkinetic gallbladder.
      All the patients had abdominal pain related to food intake and 17 (53%) patients
      had worsening of symptoms with CCK infusion. The average GBEF was 92%. Chronic
      cholecystitis was seen in 29 (90%) patients on pathology. 23 (74%) patients had
      complete resolution of biliary symptoms, 5 (16%) had improved symptoms, and 3
      (10%) had no change in symptoms. CONCLUSION: Patients with biliary colic and
      hyperkinetic gallbladder respond favorably to laparoscopic cholecystectomy. Our
      results suggest that patients with biliary colic in the setting of hyperkinetic
      gallbladder have symptomatic improvement following cholecystectomy.

PMID- 30209610
TI  - Three-way comparative study of endoscopic ultrasound-guided transmural
      gallbladder drainage using lumen-apposing metal stents versus endoscopic
      transpapillary drainage versus percutaneous cholecystostomy for gallbladder
      drainage in high-risk surgical patients with acute cholecystitis: clinical
      outcomes and success in an International, Multicenter Study.
AB  - BACKGROUND: Percutaneous cholecystostomy tube (PTGBD), endoscopic retrograde
      cholangiopancreatography with transpapillary gallbladder drainage (TP), and
      endoscopic ultrasound-guided transmural gallbladder drainage (EGBD) using lumen
      apposing metal stents (LAMS) have been offered for gallbladder decompression for
      acute cholecystitis in high-risk surgical patients. Yet, there are limited data
      comparing these therapies. Our aim was to compare the safety and efficacy of EGBD
      to TP and PTGBD for gallbladder drainage. METHODS: We retrospectively collected
      high-risk surgical patients from six centers with acute cholecystitis who
      underwent gallbladder drainage by EGBD, TP, or PTGBD. Data included technical
      success (gallbladder drainage), clinical success (acute cholecystitis
      resolution), adverse events (AE), and follow-up. RESULTS: From 2010 to 2016, 372
      patients underwent gallbladder drainage, with 146 by PTGBD, 124 by TP, and 102
      drained by EGBD. Technical (98% vs. 88% vs. 94%; p = 0.004) and Clinical (97% vs.
      90% vs. 80%; p < 0.001) success rates were significantly higher with PTGBD and
      EGBD compared to TP. PTGBD group had statistically significantly higher number of
      complications as compared to EGBD and TP groups (2 0% vs. 2% vs. 5%; p = 0.01).
      Mean hospital stay in the EGBD group was significantly less than TP and PTGBD (16
      vs. 18 vs. 19 days; p = 0.01), while additional surgical intervention was
      significantly higher in the PTGBD group compared to the EGBD and TP groups (49%
      vs. 4% vs. 11%; p < 0.0001). CONCLUSIONS: EGBD with LAMS is an effective and
      safer alternative to TP and PTGBD for treatment of patients with acute
      cholecystitis who cannot undergo surgery. EGBD with LAMS has significantly lower
      overall AEs, hospital stay, and unplanned admissions compared to PTGBD. TRIAL
      REGISTRATION: ClinicalTrials.gov Identifier: NCT01522573.

PMID- 30209611
TI  - Treatment outcomes of intracranial germinoma: a retrospective analysis of 170
      patients from a single institution.
AB  - PURPOSE: To perform a retrospective analysis of patients with intracranial
      germinoma treated in our department to evaluate treatment outcomes and determine
      optimal treatment strategies. METHODS: We reviewed the treatment outcomes of 170
      patients with intracranial germinoma who were treated in our department from
      January 1996 to January 2017. The median patient age was 15 years old. Among the
      patients, 56 (33%) were pathologically diagnosed, and 114 (67%) were diagnosed
      clinically. Various radiation fields and doses were used. Cerebrospinal fluid
      (CSF) and serum beta-human chorionic gonadotropin (beta-HCG) levels were examined
      before treatment in 114 patients. Endocrinological evaluation was performed in
      141 patients before and after treatment. A total of 38 patients received
      chemotherapy prior to radiotherapy (RT). The median follow-up time was 64.5
      months (range 4-260.5 months). RESULTS: The 5- and 10-year overall survival (OS)
      rates were 94.5% and 91.3%, respectively. The relapse-free survival (RFS) rates
      at 5- and 10-years were 91.9% and 78.1%, respectively. Relapses occurred in 18
      patients within 6 months-10 years. The spinal cord metastasis rate was 3.4% in
      patients with a localized lesion who did not receive spinal cord irradiation and
      16.7% in patients with bifocal disease who were treated using whole ventricular
      irradiation (WVI) or whole brain radiotherapy (WBRT). Treatment failure did not
      occur in patients receiving chemoradiotherapy or in patients receiving three
      dimensional conformal radiation therapy (3D-CRT)/intensity-modulated radiation
      therapy (IMRT). The RFS rate did not have a statistically significant correlation
      with the CSF/serum beta-HCG level. After RT, 19.1% of the patients developed
      newly impaired pituitary function and required hormone replacement therapy.
      CONCLUSIONS: WVI or WBRT+ primary boost (PB) is a sufficient irradiation field
      for localized intracranial germinoma, while patients with bifocal disease should
      undergo craniospinal irradiation (CSI), especially when treated with RT alone.
      CSF beta-HCG is not a prognostic marker for intracranial germinomas. The
      treatment results of chemotherapy followed by reduced-dose RT are comparable to
      those of RT alone. IMRT is recommended for intracranial germinoma to improve the
      target volume accuracy and decrease the complications of RT.

PMID- 30209612
TI  - Modified AJCC staging of gastric neuroendocrine carcinoma based on T staging can
      improve the capacity of prognosis assessment.
AB  - BACKGROUND OR PURPOSE: This study was designed to determine the value of AJCC
      staging 7th edition and improved AJCC staging in assessing the prognosis of
      gastric neuroendocrine carcinoma (GNEC). METHODS: In total, GNEC 475 patients in
      the Surveillance, Epidemiology, and End Results (SEER) database and 129 GNEC
      patients in our department undergoing resection were included. The former served
      as the test group, and the latter served as the validation group. Those with
      stage IIIb disease were allocated into four subgroups, and improved AJCC staging
      was established. The AIC and C indices were used to evaluate the capacities of
      different TNM staging. RESULTS: Significant overlap between stages IIIb and IIIa
      in both the test and validation groups was found. In the test group, T staging
      and age at disease diagnosis were independent prognostic factors for patients
      with stage IIIb. Stage IIIb was divided into T1N1, T2N1, T3N1 and T4N1, and the
      improved AJCC staging-mTNM staging was created. In mTNM staging, the IIIb
      survival curve did not cross those of stages IIIa and IIb, which had a smaller
      AIC (2490 vs. 2507) value and larger C index (0.7624 vs. 0.7450, P = 0.228).
      Similar results were obtained for the validation group. CONCLUSION: T stage was
      an independent factor influencing the prognosis of stage IIIb GNEC patients, and
      the improved AJCC staging proposed here has good prognostic value.

PMID- 30209613
TI  - Short communication: thermal regimes in hollow stems of herbaceous plants
      concepts and models.
AB  - Although there have been studies of the temperature regimes within flowers,
      micrometeorology within stems seems to have been overlooked. We present ideas,
      hypotheses, and a diagrammatic model on the biophysical and thermodynamic
      processes that interact in complex ways to result in elevated temperature regimes
      within hollow stems of herbaceous plants. We consider the effects of the ambient
      air around the stems, the possible importance of insolation, and greenhouse
      effects as influenced by stems' orientation and optical properties, i.e.,
      reflection, absorption, emissivity, translucence, pigmentation, and thermal
      conductivity. We propose that greenhouse effects contribute significantly to and
      are influenced by the above phenomena as well as by the gross anatomy
      (volume:surface ratio; wall thickness), evapotranspiration, and the thermal
      properties of the gas mixture in the lumen. We provide examples of those elevated
      temperatures that can be several degrees Celsius above the temperature of the
      surrounding atmosphere.

PMID- 30209614
TI  - Phenological calendar in some walnut genotypes grown in Romania and its
      correlations with air temperature.
AB  - Phenology is the study of periodic biological events in the plant world that are
      influenced by the environment. Temperature increase in spring season can advance
      the spring phases, but warming in autumn and winter may slow the fulfillment of
      chilling requirements and lead to later onset of spring events. This study
      examined different genotypes of walnut trees under environmental conditions, and
      measured the cold demand, heat requirements, and average time from budburst till
      flowering for 28 walnut genotypes. The information obtained provides a better
      understanding of the phenological temperature response of walnuts that will be
      useful for walnut production and will also contribute to the development of
      adaptation measures in the light of the expected climate change.

PMID- 30209615
TI  - Effects of microclimate and human parameters on outdoor thermal sensation in the
      high-density tropical context of Dhaka.
AB  - A thermal comfort questionnaire survey was carried out in the high-density,
      tropical city Dhaka. Comfort responses from over 1300 subjects were collected at
      six different sites, alongside meteorological parameters. The effect of personal
      and psychological parameters was examined in order to develop predictive models.
      Personal parameters included gender, age, activity, profession-type (indoor or
      outdoor-based), exposure to air-conditioned space and sweat-levels. Psychological
      parameters, such as 'the reason for visiting the place' and 'next destination is
      air-conditioned', had statistically significant effects on thermal sensation.
      Other parameters, such as 'body type', 'body exposure to sun', 'time living in
      Dhaka', 'travelling in last_30 min', and 'hot food' did not have any significant
      impact. Respondents' humidity, wind speed and solar radiation sensation had
      profound impacts and people were found willing to adjust to the thermal
      situations with adaptive behaviour. Based on actual sensation votes from the
      survey, empirical models are developed to predict outdoor thermal sensation in
      the case study areas. Ordinal linear regression techniques are applied for
      predicting thermal sensation by considering meteorological and personal
      conditions of the field survey. The inclusion of personal and weather opinion
      factors produced an improvement in models based on meteorological factors. The
      models were compared with the actual thermal sensation using the cross-tabulation
      technique. The predictivity of the three models (meteorological, thermos
      physiological and combined parameter) as expressed by the gamma coefficient were
      0.575, 0.636 and 0.727, respectively. In all three models, better predictability
      was observed in the 'Slightly Warm' (71% in meteorological model) and 'Hot'
      (64.9% in combined parameter model) categories-the most important ones in a hot
      humid climate.

PMID- 30209617
TI  - Significantly increased amino acid accumulation in a novel albino branch of the
      tea plant (Camellia sinensis).
AB  - MAIN CONCLUSION: A normal tea plant with one albino branch was discovered. RNA
      sequencing, albinism phenotype and ultrastructural observations provided a
      valuable understanding of the albino mechanism in tea plants. Tea plants with a
      specific color (white or yellow) have been studied extensively. A normal tea
      plant (Camellia sinensis cv. quntizhong) with one albino branch was discovered in
      a local tea plantation in Huangshan, Anhui, China. The pure albino leaves on this
      special branch had accumulated a fairly high content of amino acids, especially
      theanine (45.31 mg/g DW), and had a low concentration of polyphenols and an
      extremely low chlorophyll (Chl) content compared with control leaves.
      Ultrastructural observation of an albino leaf revealed no chloroplasts, whereas
      it was viable in the control leaf. RNA sequencing and differentially expressed
      gene (DEG) analysis were performed on the albino leaves and on control leaves
      from a normal green branch. The related genes involved in theanine and polyphenol
      biosynthesis were also investigated in this study. DEG expression patterns in Chl
      biosynthesis or degradation, carotenoid biosynthesis or degradation, chloroplast
      development, and biosynthesis were influenced in the albino leaves. Chloroplast
      deletion in albino leaves had probably destroyed the balance of carbon and
      nitrogen metabolism, leading to a high accumulation of free amino acids and a low
      concentration of polyphenols in the albino leaves. The obtained results can
      provide insight into the mechanism underlying this special albino branch
      phenotype, and are a valuable contribution toward understanding the albino
      mechanism in tea plants.

PMID- 30209616
TI  - Corn cob silica as an antibacterial support for silver nanoparticles: efficacy on
      Escherichia coli and Listeria monocytogenes.
AB  - There is great potential to combine bioresource and recycled materials with
      nanotechnology for industrial and environmental applications. In a novel
      approach, silver (Ag) nanoparticles (Ag NPs) were imbedded on amine
      functionalized silica obtained from corn cob (ACCS) to produce a composite
      material that can be used to inactivate bacteria. Transmission electron
      microscope (TEM) images show near-uniform ACCS particles (34.7 +/- 8.6 nm
      diameter), with Ag NPs (5-10 nm diameter) homogenously dispersed on the surfaces.
      The potential of ACCS-Ag NPs to rapidly inactivate gram-negative Escherichia coli
      ATCC 8739 and gram-positive Listeria monocytogenes was investigated. A four-log
      (> 99.99%) inactivation of the E. coli was achieved within 30 min with 4 mg of
      ACCS-Ag NPs in a 40-mL PBS suspension (1 * 105 CFU/mL). Extended exposure of ACCS
      Ag NP may be required to inactivate L. monocytogenes, suggesting the ACCS-Ag NP
      composite will be less practical for gram-positive bacteria due to thick cell
      wall and alternative formulations may need to be developed. Result shows that the
      potential of corn cob silica as an alternative, eco-friendly support matrix for
      applications such as bacterial inactivation. The Ag-imbedded, amine
      functionalized corn cob silica demonstrates how bio-waste can be combined with
      nanotechnology to produce useful materials.

PMID- 30209618
TI  - Distribution of natural ingredients suggests a complex network of metabolic
      transport between source and sink tissues in the brown alga Fucus vesiculosus.
AB  - MAIN CONCLUSION: Tight regulation of intra-thallus metabolite distribution in
      Fucus vesiculosus in late summer reveals the complex biochemical processes
      complying with reproduction and the preparation to the dark season. We used
      inductively coupled plasma atomic emission spectroscopy to study the tissue
      specific elemental composition, and gas chromatography coupled to mass
      spectrometry to study the distribution of small-molecular weight primary and
      secondary metabolites of the brown alga Fucus vesiculosus thalli in the
      reproductive phase. Beyond general physiological requirements, the observed
      distribution of the analysed nutrients was also found to depend on
      characteristics related to the season of harvesting, i.e., the reproductive
      period. However, a particular curious result was the high metabolic activity
      found in the stipe of the plant. In conclusion, our data not only provide
      valuable information for industrial use of fucoids targeting specific algal
      ingredients, but also give highly interesting insights in the multifaceted system
      of intra-thallus biochemical interactions during reproduction of the brown algae.

PMID- 30209619
TI  - Transcription of soybean retrotransposon SORE-1 is temporally upregulated in
      developing ovules.
AB  - MAIN CONCLUSION: Transcription of soybean retrotransposon SORE-1 was temporally
      upregulated during ovule development. This transcriptional pattern was under
      intrinsic control conferred by the long terminal repeat of SORE-1.
      Transcriptionally active retrotransposons are capable of inducing random
      disruption of genes, providing a powerful tool for mutagenesis. Activation of
      retrotransposons in reproductive cells, in particular, can lead to heritable
      changes. Here, we examined developmental control of transcription of soybean
      retrotransposon SORE-1. Transgenic Arabidopsis plants that contain beta
      glucuronidase (GUS) reporter gene fused with the SORE-1 long terminal repeat
      (LTR) had GUS staining in the ovule. Quantitative analysis of transcripts in
      plants with this DNA construct and those with the full-length SORE-1 element
      indicated a temporal upregulation of SORE-1 transcription during ovule
      development. A comparable phenomenon was also observed in soybean plants that had
      a recent insertion of this element in the GmphyA2 gene. These results provide
      evidence that the temporal upregulation of SORE-1 in the reproductive organ is
      sufficiently controlled by its LTR and indicate that the intrinsic expression
      pattern of SORE-1 is consistent with its mutagenic property.

PMID- 30209620
TI  - Feature Selection and Parameters Optimization of Support Vector Machines Based on
      Hybrid Glowworm Swarm Optimization for Classification of Diabetic Retinopathy.
AB  - Diabetic Retinopathy (DR) has been a leading cause of blindness in case of human
      beings falling between the ages of 20 and 74 years. This will have a major
      influence on both the patient and the society as it can normally influence the
      humans in their gainful years. An early DR detection is quite challenging as it
      may not be detected by humans. There are several techniques and algorithms that
      have been established for detecting the DR. These techniques have been facing
      problems to achieve effective sensitivity, accuracy, and specificity. In order to
      overcome all these problems, the work has proposed one more such effective
      algorithm for image processing in order to increase the efficiency and also
      identify easily the DR diseases. A major challenge in the task is the automatic
      detection of the microaneurysms. In this work, the Support Vector Machine (SVM)
      parameters optimized with Glowworm Swarm Optimization (GSO) and Genetic Algorithm
      (GA) is used to classify the DR. Because the SVM parameter C and gamma to control
      the performance of the classifier. For this work, the SVMs get fused with the
      hybrid GSO-GA along with the feature chromosomes that are generated that will
      thereby direct the GA search to a straight line of the error of optimal
      generalization in their super parameter space. This GSO algorithm will not have
      memory and the glow worms will not retain any information in memory. The results
      of the experiment prove that this method had achieved a better performance.

PMID- 30209621
TI  - Temperature leads to annual changes of plant community composition in alpine
      grasslands on the Qinghai-Tibetan Plateau.
AB  - In most grassland ecosystems, the effects of mean temperature increase on plant
      communities have been investigated; however, the effects of climate fluctuations
      on local plant community metrics are much less well understood. We conducted a
      nine-year survey in alpine meadow and alpine steppe to investigate the effects of
      inter-annual temperature and precipitation variation on plant community
      composition, species richness, and species diversity on the central Qinghai
      Tibetan Plateau, China. We unexpectedly found that annual variability of growing
      season temperature, and not precipitation, is a driver of plant composition and
      species diversity in both habitats. Generally, increasing temperature had a
      negative effect on species diversity in meadow (r2 = 0.94) and steppe (r2 =
      0.95). In the meadow habitat, the proportion of grass decreased with increasing
      temperature and ultimately had positive impacts on the proportion of sedges. In
      steppe habitat, legumes increased and forbs decreased with the increase of
      growing season temperature; both legumes and forbs negatively affected proportion
      of grass and resulted in grass remaining stable under temperature change. Our
      results provide evidence that responses of functional group composition and
      species richness to temporal change of temperature are very different from those
      responses to mean temperature increase on the central Qinghai-Tibetan Plateau. In
      our results, temperature is a main regulator for annual variation of functional
      group composition and species richness, while soil water content is a dominant
      regulator for community responses in other experimental warming studies.

PMID- 30209622
TI  - Tungsten disulfide (WS2) nanosheet-based photoelectrochemical aptasensing of
      chloramphenicol.
AB  - A method is described for photoelectrochemical determination of chloramphenicol
      (CLOA). It is based on the use of (a) aptamers protected with photoactive WS2
      nanosheets, and (b) DNase I-assisted target recycling. The DNA aptamer without
      label was employed for recognition of CLOA. In the absence of CLOA, the aptamer
      is adsorbed on the surface of WS2. This leads to a decrease of photocurrent due
      to the steric-hindrance effect of aptamer DNA. The adsorption of WS2 also
      protects the aptamer from digestion by DNase. In the presence of CLOA, the
      aptamer will be desorbed from the WS2 surface due to formation of an aptamer/CLOA
      conjugate. This results in an increased photocurrent due to a decreased amount of
      aptamer DNA on the electrode surface. The increase of photocurrent can be further
      improved by applying DNase triggered catalytic recycling of CLOA. Under optimal
      experimental conditions, the response is linear 10 pM - 10 nM CLOA concentration
      range, with a 3.6 pM lower detection limit (at 3sigma). This method is acceptably
      selective, accurate and stable. It was applied to the determination of CLOA in
      spiked milk samples and gave satisfactory results. Graphical abstract A simple
      and sensitive photoelectrochemical apta-biosensor was fabricated for
      chloramphenicol detection. In this work, WS2 nanosheets were employed as
      photoactive material, and DNase I catalytic chloramphenicol recycling strategy
      was adopted to amplify the detection signal.

PMID- 30209624
TI  - Surface permeability of porous media particles and capillary transport.
AB  - We have established previously, in a lead-in study, that the spreading of liquids
      in particulate porous media at low saturation levels, characteristically less
      than 10% of the void space, has very distinctive features in comparison to that
      at higher saturation levels. In particular, we have found that the dispersion
      process can be accurately described by a special class of partial differential
      equations, the super-fast non-linear diffusion equation. The results of
      mathematical modelling have demonstrated very good agreement with experimental
      observations. However, any enhancement of the accuracy and predictive power of
      the model, keeping in mind practical applications, requires the knowledge of the
      effective surface permeability of the constituent particles, which defines the
      global, macroscopic permeability of the particulate media. In the paper, we
      demonstrate how this quantity can be determined through the solution of the
      Laplace-Beltrami Dirichlet problem, we study this using the well-developed
      surface finite-element method.

PMID- 30209623
TI  - Cationic Liposomes: A Flexible Vaccine Delivery System for Physicochemically
      Diverse Antigenic Peptides.
AB  - PURPOSE: Personalized peptide-based cancer vaccines will be composed of multiple
      patient specific synthetic long peptides (SLPs) which may have various
      physicochemical properties. To formulate such SLPs, a flexible vaccine delivery
      system is required. We studied whether cationic liposomes are suitable for this
      purpose. METHODS: Fifteen SIINFEKL T cell epitope-containing SLPs, widely
      differing in hydrophobicity and isoelectric point, were separately loaded in
      cationic liposomes via the dehydration-rehydration method. Particle size and
      polydispersity index (PDI) were measured via dynamic light scattering (DLS), and
      zeta potential with laser Doppler electrophoresis. Peptide loading was
      fluorescently determined and the immunogenicity of the formulated peptides was
      assessed in co-cultures of dendritic cells (DCs) and CD8+ T-cells in vitro.
      RESULTS: All SLPs were loaded in cationic liposomes by using three different
      loading method variants, depending on the SLP characteristics. The fifteen
      liposomal formulations had a comparable size (< 200 nm), PDI (< 0.3) and zeta
      potential (22-30 mV). Cationic liposomes efficiently delivered the SLPs to DCs
      that subsequently activated SIINFEKL-specific CD8+ T-cells, indicating improved
      immunological activity of the SLPs. CONCLUSION: Cationic liposomes can
      accommodate a wide range of different SLPs and are therefore a potential delivery
      platform for personalized cancer vaccines.

PMID- 30209625
TI  - WTP and WWTP sludge management: a case study in the metropolitan area of
      Campinas, southeastern Brazil.
AB  - Disposal of sludges generated at water treatment plants (WTPs) and wastewater
      treatment plants (WWTPs) located in highly urbanized regions challenges water
      industry. Legal restrictions based on public health and sustainability push
      managers forward in order to find beneficial use markets rather than deficit and
      high-cost landfilling. A GIS-based linear optimization method for sludge
      management was firstly proposed. The metropolitan area of Campinas belongs to the
      watershed of the rivers Piracicaba, Capivari, and Jundiai (PCJ), which comprises
      76 municipalities, representing over 5 million urban consumers, supplied by 100
      WTPs and 116 WWTPs. An assessment of soils feasibility for WWTP sludge reception
      was carried out. The beneficial uses assumed to be the best for WTP and WWTP
      sludges were, respectively, addition in the industrial process of ceramic bricks
      manufacture, and application on sugarcane crop areas for ethanol production.
      Three scenarios were set for sludges from WTPs and also for WWTPs. Those
      scenarios represented maximum, intermediate, and minimum reception capability for
      each reception location or area. Ceramic industries located within PCJ watershed
      showed to be capable of receptioning the total amount of WTP sludges, if a
      minimum 2% mass/mass replacement of raw materials (mainly clay) is provided.
      There are plenty of feasible areas for WWTP sludge application; thus, sludge
      agronomic quality and farmers' acceptance constitute the only steps to climb.
      This paper brings an innovative tool regarding sludge management which may be
      useful to decision-makers, especially wherever several sources and reception
      areas are playing on game board. The proposed method can be applied at different
      locations and for other sludge uses.

PMID- 30209626
TI  - The Clinical Dilemma of Anticoagulation Use in Patients with Cerebral Amyloid
      Angiopathy and Atrial Fibrillation.
AB  - PURPOSE OF REVIEW: This review highlights current management of patients with
      concomitant cerebral amyloid angiopathy (CAA) and atrial fibrillation (AF). We
      review quantifying risk of ischemic and hemorrhagic stroke as well as treatments
      to minimize future risk. RECENT FINDINGS: Ischemic stroke risk in AF can be
      quantified by CHA2DS2-VASc and assessing left atrial echocardiographic
      characteristics. Patients deemed not low risk by CHA2DS2-VASC should be
      anticoagulated. CAA increases intracranial hemorrhage risk. CAA biomarkers
      include cortical microbleeds (CMBs), cortical superficial siderosis (cSS),
      convexal subarachnoid hemorrhage (cSAH), and lobar intracerebral hemorrhage
      (ICH). CAA with prior lobar ICH has an annual recurrence rate of 8.9%. CAA with
      cSAH carries an even higher annual lobar ICH risk of 19%. CMBs are associated
      with a dose-dependent risk of ICH, which rises with OACs. In patients with AF,
      antithrombotics should be avoided in CAA with predominant ICH, cSS, or cSAH
      features. Those with >= 2 CMB require in-depth risk-benefit analysis using a
      multidisciplinary approach.

PMID- 30209627
TI  - Mobile Learning in Medical Education.
AB  - Currently, mobile learning is a new trend in medical education. Therefore, the
      aim of this study is to examine the use of m-learning in medical education and
      discuss its effect on student learning process in order to help future medical
      professionals deliver better care for patients and populations. This was done by
      conducting a literature search in the databases Web of Science, Scopus, and
      MEDLINE, and consequently by evaluating the findings of the selected studies. The
      results of this study confirm that mobile learning is efficient, especially in
      the acquisition of new knowledge and skills. Nevertheless, so far, the role of
      mobile learning has been perceived as an appropriate complement to traditional
      learning. Therefore, more research should be conducted on the efficacy of the use
      mobile learning in medical education, as well as to explore the unique features
      of mobile devices for the enhancement of learning outcomes.

PMID- 30209628
TI  - Colorimetric detection of L-histidine based on the target-triggered self-cleavage
      of swing-structured DNA duplex-induced aggregation of gold nanoparticles.
AB  - A rapid, highly sensitive and selective colorimetric assay is presented for
      visually detecting L-histidine. It is based on L-histidine-triggered self
      cleavage of DNA duplex-induced gold nanoparticle (AuNP) aggregation. The citrate
      capped AuNPs easily aggregate in a high concentration of salt environment.
      However, in the presence of L-histidine aptamers (DNA1 and DNA2), the partial
      strands of DNA1 and DNA2 hybridize to form a DNA duplex with a swing structure.
      The swing-like DNA duplexes are adsorbed on the surface of AuNPs to improve the
      stability of AuNPs, and the AuNPs also are better dispersed in high-salt media.
      When L-histidine is added to the solutions, it catalyzes the self-cleavage of
      DNA1 to form many single-stranded DNA (ssDNA) fragments. These ssDNA segments are
      adsorbed on the AuNPs and weaken the stability of AuNPs. Hence, the AuNPs
      aggregate in high-salt environment, and this results in a red-to-blue color
      change. Under the optimized conditions, L-histidine can be determined with a
      limit of detection of 3.6 nM. In addition, the sensor was successfully applied to
      the determination of L-histidine in spiked serum samples. Graphical abstract
      Schematic of a rapid and homogeneous colorimetric L-histidine assay. It combines
      L-histidine-triggered self-cleavage of the swing-like DNA duplexes and self
      cleavage of DNA-induced AuNP aggregation.

PMID- 30209629
TI  - Cancer in Sexual and Gender Minority Patients: Are We Addressing Their Needs?
AB  - PURPOSE OF REVIEW: To describe the current literature regarding the cancer care
      of sexual and gender minority patients and to identify significant knowledge gaps
      that hinder our understanding of the unique needs of sexual and gender minority
      patients with cancer. RECENT FINDINGS: Sexual and gender minorities suffer from
      cancer-related disparities, including lower rates of cancer screening, higher
      incidence of certain cancers, and higher cancer mortality rates. Sexual side
      effects, depression, and social isolation are especially common among sexual
      minority individuals with cancer. While the aforementioned disparities are
      concerning, the cancer-specific needs of sexual and gender minorities remain
      understudied. Population-based, prospective studies evaluating cancer-specific
      risks, mortality, and survivorship issues facing gender and sexual minorities are
      lacking. There is a paucity of literature guiding the cancer care of sexual and
      gender minority patients. Areas that require further study include epidemiologic
      evaluations, cancer screening recommendations, and cancer treatment and
      survivorship.

PMID- 30209631
TI  - Cross-cultural adaptation and validation of the Italian versions of the Kujala,
      Larsen, Lysholm and Fulkerson scores in patients with patellofemoral disorders.
AB  - BACKGROUND: The Kujala, Fulkerson, Larsen and Lysholm questionnaires have been
      demonstrated to be reliable and sensitive in assessing patients with
      patellofemoral pathology. The purpose of this study is to translate and cross
      culturally adapt into Italian the English versions of the Kujala, Fulkerson,
      Larsen and Lysholm questionnaires, and undertake reliability and validity
      evaluations of the Italian versions of these scores in patients with
      patellofemoral pathology. MATERIALS AND METHODS: The cross-cultural adaptation
      process was carried out following the simplified Guillemin criteria. The
      questionnaires were administered to 63 patients with either patellar instability
      or painful patella syndrome. To assess the validity of the questionnaires, they
      were compared with the Oxford knee score. The questionnaires were administered to
      a subsample of 33 patients 5 days later to assess test-retest reliability.
      RESULTS: The interclass coefficient correlation was 0.96 for the Kujala score,
      0.92 for the Larsen score, 0.96 for the Lysholm score, 0.94 for the Fulkerson
      score (P < 0.01), and 0.83 for the Oxford score. Pearson's correlation was0.96
      between the Kujala and Oxford scores, 0.90 between the Larsen and Oxford scores,
      0.94 between the Lysholm and Oxford score, and 0.93 between the Fulkerson and
      Oxford scores. Responsiveness, calculated by standardized response mean, was 1.2,
      and effect size was 1.4. CONCLUSIONS: The Italian versions of the Kujala, Larsen,
      Lysholm and Fulkerson scoring systems were shown to be equivalent to their
      English versions and demonstrated good validity, reliability and responsiveness
      to surgical treatment of patellofemoral pathology. To the best of the authors'
      knowledge, this is the first attempt to adapt four of the most common
      patellofemoral-specific scoring scales to the Italian language. LEVEL OF
      EVIDENCE: Level II.

PMID- 30209630
TI  - Influence of Carbon Nanotubes and Its Derivatives on Tumor Cells In Vitro and
      Biochemical Parameters, Cellular Blood Composition In Vivo.
AB  - The aim of the proposed work was to analyze the toxicity of oxidized carbon
      nanotubes (CNTox), functionalized by doxorubicin (CNT-Dox) and fluorescein (CNT
      FITC) on cell and organism level. The cytotoxic effect of CNTox, CNT-Dox, and CNT
      FITC was analyzed on tumor cells in vitro (2-D, 3-D cultures) and on Balb2/c mice
      model in vivo. As a result, it was demonstrated the possibility of doxorubicin
      immobilization on the surface of CNT and controlled release of doxorubicin (Dox)
      from the surface of CNT. Dox immobilization coincident with decreasing cytotoxic
      effect CNT-Dox compared with free Dox. Breakdown of peptide bonds with CNT
      surface led to the release of doxorubicin and dose-dependent enhancement of the
      cytotoxic effect of CNTs and Dox. The combined cytotoxic effect from CNTs, Dox,
      and trypsin on the survival of tumor cells was shown. At the organism level, it
      was investigated the effect of the obtained nanostructures on the state of
      hepatic enzymatic system, the protein metabolism, and cell blood composition of
      the experimental animals. CNTox influence in vivo model was statistically the
      same as control. CNT-Dox demonstrated lower total organism toxic effect compared
      to the pure doxorubicin. Deviations in the cell blood composition indicated a
      general toxic effect of CNT-Dox, but it was more moderate compared with of pure
      doxorubicin. From the data obtained, we concluded that binding CNTs with
      doxorubicin allows reducing toxicity of the doxorubicin on the general
      biochemical indicators of blood and violations in the blood cells composition in
      vivo. At the same time, the combined effect of CNTs and doxorubicin after drug
      release allowed us to achieve greater efficacy in suppressing tumor growth in
      vitro.

PMID- 30209632
TI  - High Performance Organic-Nanostructured Silicon Hybrid Solar Cell with Modified
      Surface Structure.
AB  - Silicon nanowires (SiNWs) with excellent light trapping properties have been
      widely applied in photovoltaic devices, which provide opportunities for boosting
      the photons harvested by Si. However, the photoexcited carriers are easily
      trapped and recombined by high-density surface defects due to higher surface area
      prolonging to depth of nanowire. In this work, in order to reduce the surface
      defects and recombination rate of SiNWs, a simple solution process is used to
      modify the surface structure. Applying the tetramethyl ammonium hydroxide (TMAH)
      treatment leads to smooth and taper Si NW surface, which improves the open
      circuit voltage (Voc) and fill factor (FF) obviously. Thus, a champion PCE of
      14.08% is achieved for the nanostructured Si/PEDOT:PSS hybrid device by 60-s TMAH
      treatment. It also indicates that TMAH treatment promises a simple and effective
      method for enhancing Si NW-based devices.

PMID- 30209633
TI  - Controlling the Secondary Surface Morphology of Electrospun PVDF Nanofibers by
      Regulating the Solvent and Relative Humidity.
AB  - This work presents a simple and reliable method for directly generating
      polyvinylidene fluoride (PVDF) nanofibers with secondary surface morphology
      (e.g., porous surfaces, rough surfaces, grooved surfaces, and interior porosity)
      by using single/binary solvent systems and relative humidity. We clarified the
      mechanisms responsible for the formation of these morphologies by systematically
      exploring the molecular interactions among the polymer, solvent(s), and water
      vapor. Our results proved that the formation of secondary surface morphology
      needed the presence of water vapor, a non-solvent of the polymer, at an
      appropriate level of relative humidity. The formation of secondary surface
      morphology was dependent on the speed of evaporation of the solvent(s) (ACE, DMF,
      and their mixtures), as well as the inter-diffusion and penetration of the non
      solvent (water) and solvent(s). The results of N2 physical adsorption-desorption
      isotherms showed that the macro-porous fibers (> 300 nm) exhibited the highest
      specific surface area of 23.31 +/- 4.30 m2/g and pore volume of 0.0695 +/- 0.007
      cm3/g, enabling the high oil absorption capacities of 50.58 +/- 5.47 g/g, 37.74
      +/- 4.33 g/g, and 23.96 +/- 2.68 g/g for silicone oil, motor oil, and olive oil,
      respectively. We believe this work may serve as guidelines for the formation of
      different structures of macro-porous, rough, and grooved nanofibers with interior
      porosity through electrospinning.

PMID- 30209634
TI  - Adsorption of Transition Metals on Black Phosphorene: a First-Principles Study.
AB  - Black phosphorene is a novel two-dimensional material which has unique properties
      and wide applications. Using first-principles calculations, we investigated the
      adsorption behavior of 12 different transition metals (TMs; Fe, Co, Ni, Cu, Ru,
      Rh, Pd, Ag, Os, Ir, Pt, and Au) on phosphorene. Our results showed that all of
      the adsorption systems have a large binding energy. The Fe-, Co-, and Au
      phosphorene systems display magnetic states with magnetic moments of 2, 1, and
      0.96 MUB, respectively, which means that these systems are magnetic
      semiconductors. Adsorption of oxygen molecules on TM-phosphorene was also
      investigated. Interestingly, all the O2-(TM-phosphorene) systems, except O2-(Pd
      phosphorene), can elongate the O-O bond, which is critical to their application
      as catalysts in the oxidation of CO. We also found that the adsorption of O2
      molecules enables the O2-(Fe-, Ni-, Cu-, Ir-, Rh-, Ag-, and Au-phosphorene)
      systems to become magnetic semiconductors, and it allows O2-(Co-phosphorene) to
      display half-metallic state. Our results are expected to have important
      implications for phosphorene-based catalysis and spintronics.

PMID- 30209636
TI  - Characterization of a clinically used charcoal suspension for in vivo EPR
      oximetry.
AB  - OBJECTIVES: Electron paramagnetic resonance (EPR) oximetry using particulate
      materials allows repeatable measurements of oxygen in tissues. However, the
      materials identified so far are not medical devices, thus precluding their
      immediate use in clinical studies. The aim of this study was to assess the
      magnetic properties of Carbo-Rep(r), a charcoal suspension used as a liquid
      marker for preoperative tumor localization. MATERIALS AND METHODS: Calibration
      curves (EPR linewidth as a function of pO2) were built using 9-GHz EPR
      spectrometry. The feasibility of performing oxygen measurements was examined in
      vivo by using a low-frequency (1 GHz) EPR spectrometer and by inducing ischemia
      in the gastrocnemius muscle of mice or by submitting rats bearing tumors to
      different oxygen-breathing challenges. RESULTS: Paramagnetic centers presenting a
      high oxygen sensitivity were identified in Carbo-Rep(r). At 1 GHz, the EPR
      linewidth varied from 98 to 426 uT in L-band in nitrogen and air, respectively.
      The sensor allowed repeated measurements of oxygen over 6 months in muscles of
      mice. Subtle variations of tumor oxygenation were monitored in rats when
      switching gas breathing from air to carbogen. DISCUSSION: The magnetic properties
      of Carbo-Rep(r) are promising for its future use as oxygen sensor in clinical EPR
      oximetry.

PMID- 30209637
TI  - Ecological and human health risk assessment of toxic metals in street dusts and
      surface soils in Ahvaz, Iran.
AB  - This study aimed to examine the concentrations and environmental health risk of
      the potentially toxic metals including Pb, Zn, Cu, Cd, Cr, and As in street dusts
      and surface soils of Ahvaz, the capital of Khuzestan province, located in the
      southwest of Iran. To this end, a total of 81 street dusts and 96 surface soils
      were collected from Ahvaz urban areas. Toxic metals were measured by inductively
      coupled plasma-mass spectrometry and evaluated using enrichment factors,
      potential ecological risk index and human health risk assessment. Lead in street
      dusts and Pb and Cu in surface soil showed the highest enrichment factor. The
      results revealed that there are two major sources of toxic metals in Ahvaz,
      including industrial activities and road traffic emissions and also resuspension
      of soil and dust particles. Cu, Pb, Zn, and Cr in Ahvaz soil and dust particles
      are strongly influenced by anthropogenic activity, mainly industrial and traffic
      emissions, while As and Co originate from resuspension of soil natural parent
      particles. The potential ecological risk index (RI) values for dust samples
      indicated that 58.02% of all samples showed low potential ecological risk.
      Moreover, 33% and 9% of samples showed moderate and considerable ecological risk,
      respectively. In addition, the RI values for soil samples indicated that 57% and
      40% of all samples had low and moderate ecological risk, respectively, and 3% had
      a high ecological risk. The hazard index (HI) values of studied potentially toxic
      metals showed that there is no non-carcinogenic risk for children and adults.
      Furthermore, the HI value for children was 2-7 times upper than those for adults,
      which confirm that children show more potential health risks for exposition to
      these potential toxic metals. Cancer risks of the studied potential toxic
      elements for both adults and children decreased in the following order Crdust >
      Crsoil > Cddust > Cdsoil > Asdust > Assoil > Pbdust > Pbsoil. The carcinogenic
      risk values of Cd, As, and Pb for adults and children was lower than 1 * 10-6,
      suggesting carcinogenic risk of potentially toxic metals in the street dust and
      surface soil could be neglected. On the other hand, the carcinogenic risk value
      of Cr was greater than 1 * 10-6 for both adults and children revealing that the
      carcinogenic risks of Cr essentially need more consideration for environmental
      management control.

PMID- 30209635
TI  - Atrial Cardiopathy and Stroke Prevention.
AB  - PURPOSE OF REVIEW: Many patients with ischemic stroke have a stroke syndrome and
      neuroimaging findings consistent with embolism, but no evidence of atrial
      fibrillation. Recent data suggest that the pathological atrial substrate, or
      atrial cardiopathy, that underlies atrial fibrillation, rather than atrial
      fibrillation itself, may be an important cause of unexplained strokes. This paper
      will review the literature on the rationale and data behind the concept of atrial
      cardiopathy, its pathophysiology, suggested biomarkers of atrial cardiopathy, and
      therapeutic implications. RECENT FINDINGS: Several lines of evidence suggest that
      patients can have strokes associated with disorders of the atrium, even without
      frank atrial fibrillation. Even in patients with paroxysmal atrial fibrillation,
      cardiac emboli may occur temporally disassociated from episodes of atrial
      fibrillation, and the left atrial appendage flow patterns associated with
      increased thromboembolic risk may occur even when the surface electrocardiogram
      demonstrates normal sinus rhythm. Biomarkers of left atrial structural and
      electrophysiological abnormalities have been associated with stroke risk, even in
      the absence of atrial fibrillation. Atrial cardiopathy, as determined by the
      presence of biomarkers of left atrial dysfunction, may provide a therapeutic
      target to reduce the risk of cardioembolic stroke in the absence of atrial
      fibrillation. Clinical trials are currently ongoing to test this hypothesis.

PMID- 30209639
TI  - MicroRNA-155 Suppresses Mesangial Cell Proliferation and TGF-beta1 Production via
      Inhibiting CXCR5-ERK Signaling Pathway in Lupus Nephritis.
AB  - Increasing evidence shows miR-155 plays an important role in regulating
      inflammatory processes in systemic lupus erythematosus (SLE), especially in lupus
      nephritis (LN). Because the chemokine CXCL13 is implicated in the pathogenesis of
      LN, here we examined whether miR-155 can modulate the activity of CXCL13 or its
      receptor CXCR5. We determined the expression of CXCL13 in normal and MRL/lpr mice
      and found elevated levels of CXCL13 in the kidneys of MRL/lpr mice compared with
      normal kidneys. Besides, CXCL13 expression was mainly detected in the glomerulus,
      specifically to mesangial areas. We then transfected a miR-155 mimic in human
      renal mesangial cells (HRMCs) to overexpress miR-155 and detected decreased
      protein levels of CXCR5 by western blot analysis. Transfection of the miR-155
      mimic into CXCL13-treated HRMCs resulted in a significantly reduced proliferation
      rate of HRMCs as measured by the cell-counting assay and flow cytometry.
      Moreover, increased intracellular miR-155 also led to decreased phosphorylation
      of ERK and TGF-beta1 production. Together, these results revealed that miR-155
      may play a role in the pathogenesis of LN.

PMID- 30209638
TI  - Transcatheter Mitral Valve Therapy: Defining the Patient Who Will Benefit.
AB  - PURPOSE OF REVIEW: This report aims to define the clinical and anatomic variables
      key in determining patient suitability for transcatheter mitral valve therapies.
      RECENT FINDINGS: Candidacy for transcatheter mitral valve repair requires
      weighing the clinical variables that may impact the ability to improve patient
      symptoms and prolong survival that include left ventricular ejection fraction,
      symptom severity, pulmonary hypertension, and magnitude of residual regurgitation
      or stenosis. Individualized selection of transcatheter repair or replacement
      based on patho-anatomy is being explored. The primary goal is achieving
      significant reduction in mitral regurgitation. Transcatheter mitral valve
      replacement requires rigorous anatomic screening using computed tomography and
      candidates should be able to take oral anticoagulation. Selection of patients for
      transcatheter mitral valve repair is complex and requires intimate knowledge of
      clinical variables and specific device limitations.

PMID- 30209640
TI  - Novel method of intraoperative ocular movement monitoring using a piezoelectric
      device: experimental study of ocular motor nerve activating piezoelectric
      potentials (OMNAPP) and clinical application for skull base surgeries.
AB  - Intraoperative monitoring systems that utilize various evoked potentials for the
      detection and/or preservation of cranial nerves have become increasingly common
      due to recent technical and commercial developments, particularly during skull
      base surgeries. We established a novel system for the intraoperative monitoring
      of the extraocular motor nerves (eOMNs) using a piezoelectric device capable of
      detecting imperceptible vibrations induced by ocular movement, with sensors
      placed on the eyelids alone. We first evaluated the efficacy and reliability of
      this device for the intraoperative monitoring of eOMNs in two Beagle dogs. Based
      on the results, we then determined the appropriate stimulation parameters for use
      in human surgical cases involving removal of various skull base tumors. Animal
      experiments revealed that a 0.4 mA monopolar electrical stimulation was required
      to elicit significant responses and that these responses were not inferior to
      those obtained via the electrooculogram/electromyogram. Significant responses
      were also detected in preliminary clinical investigations in human patients,
      following both direct and indirect monopolar electrical stimulation of the
      oculomotor and abducens nerves, although obtaining responses from the trochlear
      nerve was difficult. Intraoperative monitoring using a piezoelectric device
      provides a simple and reliable method for detecting eOMNs, especially the
      oculomotor and abducens nerves. This monitoring system can be adapted to various
      surgeries for skull base tumor.

PMID- 30209641
TI  - Determination of hypoxia-inducible factor-1 by using a ratiometric colorimetric
      test based on click-mediated growth of gold nanoparticles.
AB  - The authors describe a significantly improved colorimetric nanoprobe for the
      determination of transcription factors (TFs). It is making use of click-mediated
      growth of gold nanoparticles (AuNPs) to amplify the signal-to-noise ratio.
      Hypoxia-inducible factor-1 (HIF-1) is an important TF that acts as a mediator of
      cell response to hypoxia. So, the detection of HIF-1 was chosen as the model
      analyte. Specifically, target HIF-1 is designed to bind to the hypoxia response
      element within DNA duplex. The click chemistry between the DNA duplex and alkynyl
      functionalized AuNPs (AF-AuNPs) is then inhibited because of significant steric
      hindrance. As a result, the AF-AuNPs grow into larger-sized highly-aggregated
      irregular nanostructures, which in turn enable colorimetric determination. The
      ratio of absorbances at 620 and 560 nm increases in the 0.5 to 10 nM HIF-1
      concentration range, and the detection limit is 0.27 nM. This is better by a
      factor of 100 than that of aggregation-based colorimetric assays. The nanoprobe
      is selective and can be used in complex samples. Conceivably, it may also be
      extended to the determination of other TFs by simply changing the used DNA
      duplex. Graphical abstract Schematic of a nanoprobe for detecting hypoxia
      inducible factor-1 (HIF-1). Three concepts are involved: the binding of HIF-1 and
      hypoxia response element, the Cu+-catalyzed click chemistry between P1/P2 duplex
      and alkynyl-functionalized AuNPs (AF-AuNPs), and the AuNPs growth with
      hydroxylamine and HAuCl4.

PMID- 30209644
TI  - Sympathetic and Parasympathetic Nervous System Functioning and Experiences of
      Peer Exclusion: Links to Internalizing Problems in Early Adolescence.
AB  - This study examines the moderating effect of both branches of the autonomic
      nervous system (sympathetic and parasympathetic) on associations between peer
      exclusion and internalizing behaviors. Young adolescents (N = 68) self-reported
      their perceptions of peer exclusion and internalizing problems and participated
      in stress-inducing public speaking tasks. Skin conductance and respiratory sinus
      arrhythmia were assessed at baseline (skin conductance baseline, SCLB;
      respiratory sinus arrhythmia baseline, RSAB) and during the challenge task to
      provide measures of physiological reactivity (skin conductance reactivity, SCLR;
      respiratory sinus arrhythmia reactivity, delta RSA). Youth with high delta RSA
      (low vagal suppression) had higher levels of internalizing problems when they
      perceived more peer exclusion in their social environments. The combination of
      low SCLR and high delta RSA (reciprocal parasympathetic) predicted higher levels
      of internalizing problems, whereas the combination of high SCLR and high delta
      RSA (coactivation) predicted lower levels of internalizing problems. The
      association between peer exclusion and youth internalizing problems was not
      moderated by ANS reactivity profiles which reflected combinations of SCLR and
      delta RSA.

PMID- 30209642
TI  - Is global humeral head offset related to intramedullary canal width? A computer
      tomography morphometric study.
AB  - BACKGROUND: While most anatomic TSA stems allow some intra-operative adjustments,
      the default configuration assumes that head offset is directly proportional to
      stem diameter. Some authors reported that humeral head diameter is proportional
      to intra-medullary canal width and humeral head offset, but none investigated the
      direct relationship between head offset and endosteal measurements. The purpose
      of the study was to determine whether global humeral head offset is proportional
      to intramedullary canal width at the distal metaphysis and proximal diaphysis.
      METHODS: We analyzed 100 Computed Tomography shoulder scans of patients aged 59.1
      +/- 20.5 with no signs of gleno-humeral arthritis nor humeral dysplasia. The
      width of the intramedullary diaphyseal canal was determined at four transverse
      sections 65, 70, 100 and 105 mm below the head center. The inter-observer
      agreement was excellent for intramedullary canal width (ICC = 0.96), head
      diameter (ICC = 0.97) and global head offset (ICC = 0.85). Correlations were
      analysed using Pearson's coefficients and multivariable regressions were
      performed to determine associations between head offset and five independent
      variables (gender, age, intramedullary canal width, head diameter). RESULTS:
      Global head offset was negatively correlated with head diameter (r = - 0.31, p =
      0.002), but not correlated with intramedullary canal width (r = - 0.11, p =
      0.282). Multivariable regression confirmed that global head offset was
      independently associated with head diameter (beta = - 0.15, p = 0.005), but not
      with intramedullary canal width (beta = 0.06, p = 0.431). CONCLUSIONS: The
      present study revealed that humeral offset is not correlated with intramedullary
      canal width. Implant manufacturers and shoulder surgeons should be aware of the
      subtle morphologic features, to enhance humeral stem design and restore native
      anatomy.

PMID- 30209643
TI  - Clinical outcome of left ventricular multipoint pacing versus conventional
      biventricular pacing in cardiac resynchronization therapy: a systematic review
      and meta-analysis.
AB  - Cardiac resynchronization therapy (CRT) is an effective treatment for selected
      patients with systolic heart failure. Unlike conventional biventricular pacing
      (BIP), the left ventricular multipoint pacing (MPP) can increase the number of
      left ventricular pacing sites via a quadripolar lead positioned in the coronary
      sinus. This synthetic study was conducted to integratively and quantitatively
      evaluate the clinical outcome of MPP in comparison with BIP. We systematically
      searched the databases of EMBASE, Ovid medline, and Cochrane Library through May
      2018 for studies comparing the clinical outcome of MPP with BIP in the patients
      who accepted CRT. Hospitalization for reason of heart failure, left ventricular
      eject fraction (LVEF), CRT response, all-cause morbidity, and cardiovascular
      death rate was collected for meta-analysis. A total of 11 studies with 29,606
      participants were included in this meta-analysis. Compared with BIP group, MPP
      decreased heart failure hospitalization (OR, 0.41; 95% CI, 0.33 to 0.50; P <
      0.00001), improved LVEF (mean difference, 4.97; 95% CI, 3.11 to 6.83; P <
      0.00001), increased CRT response (OR, 3.64; 95% CI, 1.68 to 7.87; P = 0.001), and
      decreased all-cause morbidity (OR, 0.41; 95% CI, 0.26-0.66; P = 0.0002) and
      cardiovascular death rate (OR, 0.21; 95% CI, 0.11-0.40; P < 0.00001). The
      published literature demonstrates that MPP was more effective than BIP in the
      heart failure patients who accepted cardiac resynchronization therapy.

PMID- 30209645
TI  - A Randomised Controlled Trial of an Information Communication Technology
      Delivered Intervention for Children with Autism Spectrum Disorder Living in
      Regional Australia.
AB  - This exploratory randomised controlled trial tested the effectiveness of a tablet
      based information communication technology early intervention application to
      augment existing therapy with the aim of improving visual motor, imitation,
      language and social skills in young children with ASD who reside in regional
      areas. Fifty-nine participants were recruited and randomised to either a therapy
      as-usual group or intervention group. With the exception of the expressive
      language subscale on the Mullen Scales of Early Learning, no significant between
      group differences were recorded for visual motor, imitation, receptive language
      and social skills of participants between baseline and post-intervention. When
      all participants were pooled and measured over time, improvements were shown in
      receptive and pragmatic language and social skills; these gains were maintained,
      thus suggesting skill acquisition.

PMID- 30209647
TI  - Utility of intraocular endoscope for lacrimal canaliculi and sac examination.
AB  - PURPOSE: Intraocular endoscope was used as a dacryoendoscope, and its
      observations and performance in lacrimal drainage system (LDS) are reported.
      METHODS: The Endo Optiks (Little Silver, New Jersey, USA), an intraocular
      endoscope (modified with customized sheath), was used for LDS visualization in
      ten normal adults and five patients with lacrimal disorders. RESULTS: We were
      able to capture high-definition images of lacrimal canaliculi and sac in all
      normal adults. Smooth whitish canalicular mucosa with lumen could be appreciated
      in all normal individuals. Common canaliculus showed variable folds among
      individuals and reddish lacrimal sac mucosa could be appreciated with great
      details. In patients with canalicular obstruction, site of obstruction was
      presented as whitish gray area with no visible lumen, which could be opened up
      precisely with trephination. No false passage was formed in any of the cases. One
      of the cases had membranous canalicular obstruction, which was opened with probe
      itself. Nasolacrimal duct could not be examined due to the shorter length of the
      probe. CONCLUSION: Intraocular endoscope can be used as high-resolution
      dacryoendoscope for visualization of lacrimal canaliculi and sac.

PMID- 30209646
TI  - Bone health in patients with inborn errors of metabolism.
AB  - Inborn errors of metabolism encompass a wide spectrum of disorders, frequently
      affecting bone. The most important metabolic disorders that primarily influence
      calcium or phosphate balance, resulting in skeletal pathology, are
      hypophosphatemic rickets and hypophosphatasia. Conditions involving bone marrow
      or affecting skeletal growth and development are mainly the lysosomal storage
      disorders, in particular the mucopolysaccharidoses. In these disorders skeletal
      abnormalities are often the presenting symptom and early recognition and
      intervention improves outcome in many of these diseases. Many disorders of
      intermediary metabolism may impact bone health as well, resulting in higher
      frequencies of osteopenia and osteoporosis. In these conditions factors
      contributing to the reduced bone mineralization can be the disorder itself, the
      strict dietary treatment, reduced physical activity or sunlight exposure and/or
      early ovarian failure. Awareness of these primary or secondary bone problems
      amongst physicians treating patients with inborn errors of metabolism is of
      importance for optimization bone health and recognition of skeletal
      complications.

PMID- 30209648
TI  - Early ophthalmologic features of Parkinson's disease: a review of preceding
      clinical and diagnostic markers.
AB  - Non-motor symptoms in Parkinson's disease are an important cause of morbidity and
      may even precede the onset of the motor features of the disease. Visual
      abnormalities are among the most frequent non-motor symptoms observed during the
      early stages of the disease. Some of the visual symptoms of Parkinson's disease
      can likely be explained by the presence of dopaminergic neurons within the
      retina, where the progressive loss of dopamine and the accumulation of alpha
      synuclein within the retinal layers leads to visual dysfunction, while some are
      caused by abnormalities in cortical visual processing. Many of these visual
      symptoms can be overlooked or go unrecognized. We review the visual symptoms in
      Parkinson's disease, including visual-processing and ocular motility
      abnormalities, stereopsis deficits, and visual hallucinations, focusing on the
      early stages of the disease. We focus on the reciprocal influence between the
      visual symptoms and the progression of the disease, analyzing the influence of
      dopaminergic therapy on the visual abnormalities. Finally, we discuss the
      possible role of some of these visual symptoms as possible markers or early
      diagnostic signs of the disease.

PMID- 30209649
TI  - Differential effects of propranolol on head and upper limb tremor in patients
      with essential tremor and dystonia.
AB  - Propranolol is used as the first-line treatment in essential tremor and it has
      also been proposed as a treatment for tremor in dystonia. However, several issues
      remain uncertain. For example, it is still not clear whether propranolol exerts a
      beneficial effect on head tremor. Moreover, no studies have investigated whether
      the effect of propranolol on head and upper limb tremor in essential tremor
      differs from that in dystonia. We aimed to assess the effects of propranolol on
      tremor in different body parts in essential tremor and in patients with tremor
      and dystonia. Twenty-nine patients with head and upper limb tremor were enrolled
      in the study, 14 with essential tremor, and 15 with dystonia. Participants
      underwent a clinical and kinematic analysis of tremor in two sessions, i.e.,
      without (baseline) and 'on therapy' with propranolol. We found that head tremor
      was more severe in patients with dystonia, while upper limb tremor was more
      evident in patients with essential tremor (P < 0.05). Propranolol had no effect
      on head tremor in either group (all Ps > 0.05), but it did reduce upper limb
      tremor in patients with essential tremor. The present study demonstrates
      differential effects of propranolol on head and upper limb tremor in patients
      with essential tremor. The lack of effect on head and upper limb tremor in
      patients with dystonia suggests that the pathophysiological mechanisms underlying
      tremor in these two conditions and in different body parts may be distinct.

PMID- 30209650
TI  - Platelet-derived extracellular vesicles in Huntington's disease.
AB  - The production and release of extracellular vesicles (EV) is a property shared by
      all eukaryotic cells and a phenomenon frequently exacerbated in pathological
      conditions. The protein cargo of EV, their cell type signature and availability
      in bodily fluids make them particularly appealing as biomarkers. We recently
      demonstrated that platelets, among all types of blood cells, contain the highest
      concentrations of the mutant huntingtin protein (mHtt)-the genetic product of
      Huntington's disease (HD), a neurodegenerative disorder which manifests in
      adulthood with a complex combination of motor, cognitive and psychiatric
      deficits. Herein, we used a cohort of 59 HD patients at all stages of the
      disease, including individuals in pre-manifest stages, and 54 healthy age- and
      sex-matched controls, to evaluate the potential of EV derived from platelets as a
      biomarker. We found that platelets of pre-manifest and manifest HD patients do
      not release more EV even if they are activated. Importantly, mHtt was not found
      within EV derived from platelets, despite them containing high levels of this
      protein. Correlation analyses also failed to reveal an association between the
      number of platelet-derived EV and the age of the patients, the number of CAG
      repeats, the Unified Huntington Disease Rating Scale total motor score, the Total
      Functional Capacity score or the Burden of Disease score. Our data would,
      therefore, suggest that EV derived from platelets with HD is not a valuable
      biomarker in HD.

PMID- 30209653
TI  - Derivation of Neural Stem Cells from the Developing and Adult Human Brain.
AB  - Neural stem cells isolated from the developing and adult brain are an ideal
      source of cells for use in clinical applications such as cell replacement
      therapy. The clear advantage of these cells over the more commonly utilised
      embryonic and pluripotent stem cells is that they are already neurally committed.
      Of particular importance is the fact that these cells don't require the same
      level of in vitro culture that can be cost and labour intensive. Foetal neural
      stem cells can be readily derived from the foetal brain and expand in culture
      over time. Similarly, adult stem cells have been explored for their potential in
      vitro and in vivo animal models. In this chapter we identify the progress made in
      developing these cells as well as the advantages of taking them forward for
      clinical use.

PMID- 30209654
TI  - Human Somatic Stem Cell Neural Differentiation Potential.
AB  - Human somatic stem cells can be identified and isolated from different types of
      tissues and are grouped here based on their developmental maturation and ability
      to undergo neural differentiation. The first group will represent afterbirth
      somatic tissues, which are perinatal stem cells including placental blood and
      tissue, amniotic fluid and tissue, and umbilical cord blood- and umbilical cord
      tissue-derived cells. The second group of cells discussed in this chapter is the
      adult stem cells, generally those in a transient period of development, thus
      placing them in the special position of transitioning from the perinatal to young
      somatic tissue, and they include the menstrual blood-, the peripheral blood-, and
      the bone marrow-derived stem cells.

PMID- 30209655
TI  - Neural Stem Cells Derived from Human-Induced Pluripotent Stem Cells and Their Use
      in Models of CNS Injury.
AB  - Induced pluripotent stem (iPS) cells are derived from differentiated cells by
      different reprogramming techniques, by introducing specific transcription factors
      responsible for pluripotency. Induced pluripotent stem cells can serve as an
      excellent source for differentiated neural stem/progenitor cells (NSCs/NPs).
      Several methods and protocols are utilized to create a robust number of NSCs/NPs
      without jeopardizing the safety issues required for in vivo applications. A
      variety of disease-specific iPS cells have been used to study nervous system
      diseases. In this chapter, we will focus on some of the derivation and
      differentiation approaches and the application of iPS-NPs in the treatment of
      spinal cord injury and stroke.

PMID- 30209652
TI  - Dorsal root ganglia in vivo morphometry and perfusion in female patients with
      Fabry disease.
AB  - PURPOSE: To examine dorsal root ganglia and the proximal nerve segments in female
      patients with Fabry disease by functional and morphometric magnetic resonance
      neurography. METHODS: In this prospective multicenter study the lumbosacral
      dorsal root ganglia and proximal sciatic nerve were examined in ten female
      patients with Fabry disease by a standardized magnetic resonance neurography
      protocol at 3 T. Volumes of dorsal root ganglia L3-S2, permeability of dorsal
      root ganglia L5 and S1 and the spinal nerve L5 as well as the cross-sectional
      area of the proximal sciatic nerve were compared to 16 gender-matched healthy
      controls. RESULTS: Dorsal root ganglia were symmetrically enlarged by 54% (L3),
      79% (L4), 60% (L5), 94% (S1), and 106% (S2) (p < 0.001). Additionally,
      permeability of the blood-tissue interface was decreased by 47% (p < 0.001). This
      finding was most pronounced in the peripheral zone of the dorsal root ganglia,
      where the cell bodies of the primary sensory neurons are located (p < 0.001).
      While spinal nerve permeability showed no differences compared to healthy
      controls, proximal sciatic nerve cross-sectional area was mildly increased by 6%
      (p < 0.01). CONCLUSION: Although heterozygous, Fabry females show severe enlarged
      dorsal root ganglia with a concomitant dysfunctional perfusion, even in patients
      with minor disease progression and in patients who are not considered for enzyme
      replacement therapy yet. Alterations in dorsal root ganglia volume and perfusion
      might serve as a very early in vivo marker for involvement of the peripheral
      nervous system in Fabry disease, even in patients with residual enzyme activity.

PMID- 30209651
TI  - Quality of life in a German cohort of Parkinson's patients assessed with three
      different measures.
AB  - BACKGROUND: Parkinson's disease (PD) is characterized by severe motor and non
      motor symptoms reducing patients' quality of life (QoL). Instruments have been
      well established for QoL assessments in PD, including the EuroQol (EQ-5D), the
      Parkinson's disease questionnaire (PDQ-39), or rather uncommon, like the WHOQOL
      100. So far, the impact of variables has been investigated for each of these
      measures separately in different study populations, limiting the comparability of
      the results. Thus, this study compared the EQ-5D, PDQ-39, and the WHOQOL-100
      (with its short-form WHOQOL-BREF) in the same study population. METHODS: Seventy
      five PD outpatients were assessed in a prospective study, including disease
      severity according to Hoehn and Yahr stage (HY) and Unified Parkinson Disease
      Rating Scale (UPDRS). The Geriatric Depression Scale (GDS-15) screened for
      depression. RESULTS: Decreased QoL was found with all three instruments. In
      multivariate models, sex and treatment complications had an impact on QoL
      according to all three measures, while duration of PD and HY was not associated
      with QoL in any of them. Depression was relevant for the WHOQOL-100/WHOQOL-BREF
      and the PDQ-39, but not for the EQ-5D. The total variances explained by the
      WHOQOL-100, WHOQOL-BREF, PDQ-39, and the EQ-5D were 0.27, 0.34, 0.70, and 0.50,
      respectively. CONCLUSIONS: The associations between clinical aspects of PD and
      QoL vary substantially among all three measures. Importantly, depression as a
      frequent comorbidity in PD is underestimated by the EQ-5D, but not by the PDQ-39
      and the WHOQOL-100/WHOQOL-BREF. In turn, motor impairments are underestimated by
      the latter and associated strongest with QoL in the EQ-5D.

PMID- 30209656
TI  - Generation of Human Neural Stem Cells by Direct Phenotypic Conversion.
AB  - Human neural stem cells (hNSC) are multipotent adult stem cells. Various studies
      are underway worldwide to identify new methods for treatment of neurological
      diseases using hNSC. This chapter summarizes the latest research trends in and
      fields for application of patient-specific hNSC using direct phenotypic
      conversion technology. The aim of the study was to analyze the advantages and
      disadvantages of current technology and to suggest relevant directions for future
      hNSC research.

PMID- 30209657
TI  - Epigenetic Regulation of Human Neural Stem Cell Differentiation.
AB  - Emerging evidence has demonstrated that epigenetic programs influence many
      aspects of neural stem cell (NSC) behavior, including proliferation and
      differentiation. It is becoming apparent that epigenetic mechanisms, such as DNA
      methylation, histone modifications, and noncoding RNA expression, are
      spatiotemporally regulated and that these intracellular programs, in concert with
      extracellular signals, ensure appropriate gene activation. Here we summarize
      recent advances in understanding of the epigenetic regulation of human NSCs
      directly isolated from the brain or produced from pluripotent stem cells
      (embryonic and induced pluripotent stem cells, respectively).

PMID- 30209658
TI  - Induced Pluripotent Stem Cells Reveal Common Neurodevelopmental Genome
      Deprograming in Schizophrenia.
AB  - Schizophrenia is a neurodevelopmental disorder characterized by complex
      aberrations in the structure, wiring, and chemistry of multiple neuronal systems.
      The abnormal developmental trajectory of the brain is established during
      gestation, long before clinical manifestation of the disease. Over 200 genes and
      even greater numbers of single nucleotide polymorphisms and copy number
      variations have been linked with schizophrenia. How does altered function of such
      a variety of genes lead to schizophrenia? We propose that the protein products of
      these altered genes converge on a common neurodevelopmental pathway responsible
      for the development of brain neural circuit and neurotransmitter systems. The
      results of a multichanneled investigation using induced pluripotent stem cell
      (iPSCs)- and embryonic stem cell (ESCs)-derived neuronal committed cells (NCCs)
      indicate an early (preneuronal) developmental-genomic etiology of schizophrenia
      and that the dysregulated developmental gene networks are common to genetically
      unrelated cases of schizophrenia. The results support a "watershed" mechanism in
      which mutations within diverse signaling pathways affect the common pan-ontogenic
      mechanism, integrative nuclear (n)FGFR1 signaling (INFS). Dysregulation of INFS
      in schizophrenia NCCs deconstructs coordinated gene networks and leads to
      formation of new networks by the dysregulated genes. This genome deprograming
      affects critical gene programs and pathways for neural development and functions.
      Studies show that the genomic deprograming reflect an altered nFGFR1-genome
      interactions and deregulation of miRNA genes by nFGFR1. In addition, changes in
      chromatin topology imposed by nFGFR1 may play a role in coordinate gene
      dysregulation in schizophrenia.

PMID- 30209659
TI  - Genome Editing in Human Neural Stem and Progenitor Cells.
AB  - Experimental tools for precise manipulation of mammalian genomes enable reverse
      genetic approaches to explore biology and disease. Powerful genome editing
      technologies built upon designer nucleases, such as CRISPR/Cas9, have recently
      emerged. Parallel progress has been made in methodologies for the expansion and
      differentiation of human pluripotent and tissue stem cells. Together these
      innovations provide a remarkable new toolbox for human cellular genetics and are
      opening up vast opportunities for discoveries and applications across the breadth
      of life sciences research. In this chapter, we review the emergence of genome
      editing technologies and how these are being deployed in studies of human
      neurobiology, neurological disease, and neuro-oncology. We focus our discussion
      on CRISPR/Cas9 and its application in studies of human neural stem and progenitor
      cells.

PMID- 30209661
TI  - Bioengineering of the Human Neural Stem Cell Niche: A Regulatory Environment for
      Cell Fate and Potential Target for Neurotoxicity.
AB  - Human neural stem/progenitor cells of the developing and adult organisms are
      surrounded by the microenvironment, so-called neurogenic niche. The developmental
      processes of stem cells, such as survival, proliferation, differentiation, and
      fate decisions, are controlled by the mutual interactions between cells and the
      niche components. Such interactions are tissue specific and determined by the
      biochemical and biophysical properties of the niche constituencies and the
      presence of other cell types. This dynamic approach of the stem cell niche, when
      translated into in vitro settings, requires building up "biomimetic"
      microenvironments resembling natural conditions, where the stem/progenitor cell
      is provided with diverse extracellular signals exerted by soluble and structural
      cues, mimicking those found in vivo. The neural stem cell niche is characterized
      by a unique composition of soluble components including neurotransmitters and
      trophic factors as well as insoluble extracellular matrix proteins and
      proteoglycans. Biotechnological innovations provide tools such as a new
      generation of tunable biomaterials capable of releasing specific signals in a
      spatially and temporally controlled manner, thus creating in vitro nature-like
      conditions and, when combined with stem cell-derived tissue specific progenitors,
      producing differentiated neuronal tissue structures. In addition, substantial
      progress has been made on the protocols to obtain stem cell-derived cell
      aggregates such as neurospheres and self-assembled organoids.In this chapter, we
      have assessed the application of bioengineered human neural stem cell
      microenvironments to produce in vitro models of different levels of biological
      complexity for the efficient control of stem cell fate. Examples of biomaterial
      supported two-dimensional and three-dimensional (2D and 3D) complex culture
      systems that provide artificial neural stem cell niches are discussed in the
      context of their application for basic research and neurotoxicity testing.

PMID- 30209660
TI  - Brain Organoids: Expanding Our Understanding of Human Development and Disease.
AB  - Stem cell-derived brain organoids replicate important stages of the prenatal
      human brain development and combined with the induced pluripotent stem cell
      (iPSC) technology offer an unprecedented model for investigating human
      neurological diseases including autism and microcephaly. We describe the history
      and birth of organoids and their application, focusing on cerebral organoids
      derived from embryonic stem cells and iPSCs. We discuss new insights into
      organoid-based model of schizophrenia and shed light on challenges and future
      applications of organoid-based disease model system. This review also suggests
      hitherto unrevealed potential applications of organoids in combining with new
      technologies such as nanophotonics/optogenomics for controlling brain development
      and atomic force microscopy for studying mechanical forces that shape the
      developing brain.

PMID- 30209663
TI  - Human Neural Stem Cells for Ischemic Stroke Treatment.
AB  - Ischemic stroke is the second most common cause of death worldwide and a major
      cause of disability. It takes place when the brain does not receive sufficient
      blood supply due to the blood clot in the vessels or narrowing of vessels' inner
      space due to accumulation of fat products. Apart from thrombolysis (dissolving of
      blood clot) and thrombectomy (surgical removal of blood clot or widening of
      vessel inner area) during the first hours after an ischemic stroke, no effective
      treatment to improve functional recovery exists in the post-ischemic phase. Due
      to their narrow therapeutic time window, thrombolysis and thrombectomy are
      unavailable to more than 80% of stroke patients.Many experimental studies carried
      out in animal models of stroke have demonstrated that stem cell transplantation
      may become a new therapeutic strategy in stroke. Transplantation of stem cells of
      different origin and stage of development has been shown to lead to improvement
      in experimental models of stroke through several mechanisms including neuronal
      replacement, modulation of cellular and synaptic plasticity and inflammation,
      neuroprotection and stimulation of angiogenesis. Several clinical studies and
      trials based on stem cell delivery in stroke patients are in progress with goal
      of improvements of functional recovery through mechanisms other than neuronal
      replacement. These approaches may provide therapeutic benefit, but generation of
      specific neurons for reconstruction of stroke-injured neural circuitry remains
      ultimate challenge. For this purpose, neural stem cells could be developed from
      multiple sources and fated to adopt required neuronal phenotype.

PMID- 30209662
TI  - Updates on Human Neural Stem Cells: From Generation, Maintenance, and
      Differentiation to Applications in Spinal Cord Injury Research.
AB  - Human neural stem cells (hNSCs) and human induced pluripotent stem cells (hiPSCs)
      have been the primary focuses in basic science and translational research as well
      as in investigative clinical applications. Therefore, the capability to perform
      reliable derivation, effective expansion, and long-term maintenance of
      uncommitted hNSCs and hiPSCs and their targeted phenotypic differentiations
      through applying chemically and biologically defined medium in vitro is essential
      for expanding and enriching the fundamental and technological capacities of stem
      cell biology and regenerative medicine. In this chapter, we systematically
      summarized a set of protocols and unique procedures that have been developed in
      the laboratories of Prof. Teng and his collaborators. These regimens have been,
      over the years, reproducibly and productively used to derive, propagate,
      maintain, and differentiate hNSCs, including those derived from hiPSCs. We
      emphasize the multimodal methodologies that were pioneered and established in our
      laboratories for characterizing functional multipotency of stem cells and its
      value in basic science as well as translational biomedical studies.

PMID- 30209665
TI  - Neural Stem Cell Dysfunction in Human Brain Disorders.
AB  - Neural stem cells (NSCs) give rise to the entire nervous system. Animal models
      suggest that defects in NSC proliferation and differentiation contribute to
      several brain disorders (e.g., microcephaly, macrocephaly, autism, schizophrenia,
      and Huntington's disease). However, animal models of such diseases do not fully
      recapitulate all disease-related phenotypes because of substantial differences in
      brain development between rodents and humans. Therefore, additional human-based
      evidence is required to understand the mechanisms that are involved in the
      development of neurological diseases that result from human NSC (hNSC)
      dysfunction. Human-induced pluripotent stem cells provide a new model to
      investigate the contribution of hNSCs to various neurological pathologies. In
      this chapter, we review the role of hNSCs in both neurodevelopment- and
      neurodegeneration-related human brain pathologies, with an emphasis on recent
      evidence that has been obtained using embryonic stem cell- or induced pluripotent
      stem cell-derived hNSCs and progenitors.

PMID- 30209664
TI  - Modeling Complex Neurological Diseases with Stem Cells: A Study of Bipolar
      Disorder.
AB  - The pathogenesis of bipolar disorder (BPD) is unknown. Using human-induced
      pluripotent stem cells (hiPSCs) to unravel pathological mechanisms in polygenic
      diseases is challenging, with few successful studies to date. However, hiPSCs
      from BPD patients responsive to lithium have offered unique opportunities to
      discern lithium's mechanism of action and hence gain insight into BPD pathology.
      By profiling the proteomics of BPD-hiPSC-derived neurons, we found that lithium
      alters the phosphorylation state of collapsin response mediator protein-2
      (CRMP2). The "set point" for the ratio of pCRMP2:CRMP2 is elevated uniquely in
      hiPSC-derived neurons from lithium responsive (Li-R) BPD patients, but not other
      psychiatric and neurological disorders. Utilizing neurons differentiated from
      human patient stem cells as an in vitro platform, we were able to elucidate the
      mechanism driving the pathogenesis and pathophysiology of lithium-responsive BPD,
      heretofore unknown. Importantly, the findings in culture were validated in human
      postmortem material as well as in animal models of BPD behavior. These data
      suggest that the "lithium response pathway" in BPD governs CRMP2's
      phosphorylation, which regulates cytoskeletal organization, particularly in
      dendritic spines, leading to modulated neural networks that may underlie Li-R BPD
      pathogenesis. This chapter reviews the methodology of leveraging a functional
      agent, lithium, to identify unknown pathophysiological pathways with hiPSCs and
      how to translate this disease modeling approach to other neurological disorders.

PMID- 30209666
TI  - Human Fetal Neural Stem Cells for Neurodegenerative Disease Treatment.
AB  - Clinical trials for Parkinson's disease, which used primary brain fetal tissue,
      have demonstrated that neural stem cell therapy could be suitable for
      neurodegenerative diseases. The use of fetal tissue presents several issues that
      have hampered the clinical development of this approach. In addition to the
      ethical concerns related to the required continuous supply of fetal specimen, the
      necessity to use cells from multiple fetuses in a single graft greatly compounded
      the problem. Cell viability and composition vary in different donors, and,
      further, the heterogeneity in the donor cells increased the probability of
      immunological rejection or contamination. An ideal cell source for cell therapy
      is one that is renewable, thus eliminating the need for transplantation of
      primary fetal tissue, and that also allows for viability, sterility, cell
      composition, and cell maturation to be controlled, while being inherently not
      tumorigenic. The availability of continuous and standardized clinical grade
      normal human neural cells, able to combine the plasticity of fetal tissue with an
      extensive proliferating capacity and functional stability, would be of paramount
      importance for the translation of cell therapy for central nervous system (CNS)
      disorders into the clinic. Here we describe a well-established protocol to
      produce human neural stem cells following GMP guidelines that allows us to obtain
      "clinical grade" cell lines.

PMID- 30209667
TI  - The spin filtering effect and negative differential behavior of the graphene
      pentalene-graphene molecular junction: a theoretical analysis.
AB  - Density functional theory (DFT) combined with nonequilibrium Green's function
      (NEGF) formalism are used to investigate the effects of substitutional doping by
      nitrogen and sulfur on transport properties of AGNR-pentalene-AGNR nanojunction.
      A considerable spin filtering capability in a wide bias range is observed for all
      systems, which may have potential application in spintronics devices. Moreover,
      all model devices exhibit a negative differential effect with considerable peak
      to-valley ratio. Thus, our findings provide a way to produce multifunctional
      spintronic devices based on nitrogen and sulfur doped pentalene-AGNR
      nanojunctions. The underlying mechanism for this interesting behavior was exposed
      by analyzing the transmission spectrum as well as the electrostatic potential
      distribution. In addition, a system doped with an odd number of dopant shows a
      rectifying efficiency comparable to other systems. The above findings strongly
      imply that such a multifunctional molecular device would be a useful candidate
      for molecular electronics. Graphical abstract The graphene-pentalene-graphene
      molecular junction.

PMID- 30209668
TI  - Predicting Patient No-show Behavior: a Study in a Bariatric Clinic.
AB  - PURPOSE: No-shows of patients to their scheduled appointments have a significant
      impact on healthcare systems, including lower clinical efficiency and higher
      costs. The purpose of this study was to investigate the factors associated with
      patient no-shows in a bariatric surgery clinic. MATERIALS AND METHODS: We
      performed a retrospective study of 13,230 records for 2660 patients in a clinic
      located in Rio de Janeiro, Brazil, over a 17-month period (January 2015-May
      2016). Logistic regression analyses were conducted to explore and model the
      influence of certain variables on no-show rates. This work also developed a
      predictive model stratified for each medical specialty. RESULTS: The overall
      proportion of no-shows was 21.9%. According to multiple logistic regression,
      there is a significant association between the patient no-shows and eight
      variables examined. This association revealed a pattern in the increase of
      patient no-shows: appointment in the later hours of the day, appointments not in
      the summer months, post-surgery appointment, high lead time, higher no-show
      history, fewer numbers of previous appointments, home address 20 to 50 km away
      from the clinic, or scheduled for another specialty other than a bariatric
      surgeon. Age group, forms of payment, gender, and weekday were not significant
      predictors. Predictive models were developed with an accuracy of 71%. CONCLUSION:
      Understanding the characteristics of patient no-shows allows making improvements
      in management practice, and the predictive models can be incorporated into the
      clinic dynamic scheduling system, allowing the use of a new appointment policy
      that takes into account each patient's no-show probability.

PMID- 30209669
TI  - Seasonal and sex differences in the fission-fusion dynamics of spider monkeys
      (Ateles geoffroyi yucatanensis) in Belize.
AB  - Spider monkeys (Ateles sp.) are characterized by high fission-fusion dynamics,
      meaning their social grouping pattern is fluid and consists of subgroups that
      vary in size, composition, and spatial cohesion over time. In this study, we
      quantify the fission-fusion dynamics of a group of spider monkeys at Runaway
      Creek Nature Reserve in Belize by measuring subgroup size, spatial cohesion, and
      stability using data spanning 5 years. We then test whether variation in these
      three subgroup measures differ according to season, subgroup sex composition, and
      the reproductive status of female subgroup members. Our results show that
      subgroups were larger in size and less stable in membership during the wet season
      compared to the dry season. All-female subgroups were less spatially cohesive but
      more stable in membership than all-male subgroups. Finally, we report that
      subgroups with one or more non-lactating females (i.e., without nursing young)
      were smaller on average than subgroups containing lactating females with nursing
      young. These data contribute to a growing body of research documenting the
      ecological and social dimensions along which grouping patterns might vary.

PMID- 30209670
TI  - A Zr(IV)-based porphyrinic metal-organic framework as a solid-phase sorbent for
      extraction of sulfonamides prior to their quantitation by LC-MS.
AB  - A porphyrinic metal-organic framework (PCN-224) was fabricated and used as an
      adsorbent for solid-phase extraction of ultratrace levels of polar sulfonamide
      antibiotics from food and drinking waters. The PCN-224 was characterized by
      scanning electron microscopy, Fourier transform infrared spectroscopy, and powder
      X-ray diffraction analyses. Parameters affecting the extraction efficiency were
      optimized. The sulfonamides were quantified by liquid chromatography-tandem mass
      spectrometry. Figures of merit include (a) low limits of detection (0.07-0.47
      ng.L-1), (b) wide linear ranges (0.5-2000 ng.L-1), and (c) good repeatabilities
      (2.8%-6.7%) and reproducibilities (1.7%-5.1%). The method was successfully
      applied to the determination of sulfonamides in food and drinking water samples.
      Graphical abstract A Zr(IV)-based porphyrinic metal-organic framework (PCN-224)
      was synthesized from a Zr6 cluster and the H2TCPP ligand. It was used for solid
      phase extraction of sulfonamides from food and drinking water samples coupled
      with liquid chromatography-tandem mass spectrometry (LC-MS/MS) for determination.

PMID- 30209672
TI  - A video-based training to effectively teach CPR with long-term retention: the
      ScuolaSalvaVita.it ("SchoolSavesLives.it") project.
AB  - Enhancing CPR knowledge in schools is the key to improving bystander CPR rate and
      survival after an out-of-hospital cardiac arrest, but the best method to do so in
      a whole area is unknown. We wanted to assess if a province-based project, which
      involves the Secondary Schools of a whole Province, is effective in teaching
      schoolchildren CPR, and how well the skills are retained. We trained 100 teachers
      from the 21 Secondary Schools of the Province of Pavia with a BLS/AED course and
      we supplied each school with 10 low-budget manikins and four educational videos.
      These videos, about 2 min each, consist of a motivational part, an instructive
      part, a demonstrative part and a practice-while-watching part. We explained to
      the teachers how to use manikins and videos in a 2-h course. We carried out both
      a theoretical and a practical test in 21 classes, randomly selected between the
      classes trained by the teachers, 3 months and 6 months after the training. In the
      first 5 months of the project, 5146 schoolchildren aged 14-19, in the 21
      Secondary Schools of our Province, were trained by their teachers. We tested 304
      students 3 months after the course and 318 students 6 months after the course,
      with good results both in theoretical and practical skills. Our study
      demonstrates that the ScuolaSalvaVita project is able to effectively teach CPR
      through teachers using a video-based training in the Secondary Schools of a whole
      Province obtaining good long-term memory of CPR skills.

PMID- 30209674
TI  - Behavioral Health Assessments and Interventions of Psychology Trainees and
      Residents During Dual Interviewing: Replication and Extension.
AB  - The integration of psychologists and other behavioral health providers in primary
      care practice continues to evolve and reshape approaches to patient care. This
      study is a replication and extension of a 2013 study describing dual interviewing
      encounters involving psychology trainees and family medicine residents within an
      integrated primary care clinic as it relates to behavioral health assessments and
      interventions. Psychology trainees provided descriptions of 400 collaborative
      patient encounters involving 337 single and 63 repeat encounters. Psychology
      trainees coded the frequency of behavioral health assessments and interventions
      by the psychology trainee, family medicine resident, or both. Seventy-eight
      percent of encounters contained an assessment, and 20% contained interventions.
      Compared to the 2013 study, there were significantly fewer behavioral health
      interventions offered and a significantly greater number of
      psychoeducation/supportive interventions offered collaboratively. It was
      discovered that discussions between psychology trainees and family medicine
      residents immediately after patient encounters occurred 50% of the time and
      involved issues of case conceptualization. These informal discussions may be an
      important source of behavioral health education for family medicine residents.
      This study adds to efforts to better understand what occurs during these
      encounters.

PMID- 30209671
TI  - Lipomyces starkeyi: an emerging cell factory for production of lipids,
      oleochemicals and biotechnology applications.
AB  - Oils and oleochemicals produced by microbial cells offer an attractive
      alternative to petroleum and food-crop derived oils for the production of
      transport fuel and oleochemicals. An emerging candidate for industrial single
      cell oil production is the oleaginous yeast Lipomyces starkeyi. This yeast is
      capable of accumulating storage lipids to concentrations greater than 60% of the
      dry cell weight. From the perspective of industrial biotechnology L. starkeyi is
      an excellent chassis for single-cell oil and oleochemical production as it can
      use a wide variety of carbon and nitrogen sources as feedstock. The strain has
      been used to produce lipids from hexose and pentose sugars derived from
      cellulosic hydrolysates as well as crude glycerol and even sewage sludge. L.
      starkeyi also produces glucanhydrolases that have a variety of industrial
      applications and displays potential to be employed for bioremediation. Despite
      its excellent properties for biotechnology applications, adoption of L. starkeyi
      as an industrial chassis has been hindered by the difficulty of genetically
      manipulating the strain. This review will highlight the industrial potential of
      L. starkeyi as a chassis for the production of lipids, oleochemicals and other
      biochemicals. Additionally, we consider progress and challenges in engineering
      this organism for industrial applications.

PMID- 30209673
TI  - Alteration in NMDA Receptor Mediated Glutamatergic Neurotransmission in the
      Hippocampus During Senescence.
AB  - Glutamate is the primary excitatory neurotransmitter in neurons and glia. N
      methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
      acid (AMPA), and kainate receptors are major ionotropic glutamate receptors.
      Glutamatergic neurotransmission is strongly linked with Ca2+ homeostasis.
      Research has provided ample evidence that brain aging is associated with altered
      glutamatergic neurotransmission and Ca2+ dysregulation. Much of the work has
      focused on the hippocampus, a brain region critically involved in learning and
      memory, which is particularly susceptible to dysfunction during senescence. The
      current review examines Ca2+ regulation with a focus on the NMDA receptors in the
      hippocampus. Integrating the knowledge of the complexity of age-related
      alterations in Ca2+ homeostasis and NMDA receptor-mediated glutamatergic
      neurotransmission will positively shape the development of highly effective
      therapeutics to treat brain disorders including cognitive impairment.

PMID- 30209675
TI  - Feasibility of Including Behavioral Feeding Training Within a Parent Intervention
      for Young Children With Type 1 Diabetes.
AB  - Young children with T1D frequently display challenging eating behaviors
      interfering with diabetes management. The current study explored the feasibility
      and acceptability of a behavioral parent feeding training session with young
      children with type 1 diabetes. As part of a larger intervention pilot focused on
      healthy eating and physical activity, 9 young children (Mage = 4.22) with type 1
      diabetes (T1D) and their mothers participated in a novel/non-preferred food
      training session. Parents were taught strategies and then were given an
      opportunity to use the strategies with their child. The paradigm was video
      recorded and content was coded for parent and child behavior. Feasibility was
      high, and all parents rated the feeding session as acceptable. All parents
      demonstrated using at least one behavioral feeding skill (M = 3.38, SD = 1.60).
      All 9 (100%) children touched at least one of their non-preferred foods (M =
      2.05, SD = 0.75), and 5 (56%) ate at least one novel/non-preferred food (M =
      1.65, SD = 0.87). Parents of young children with T1D demonstrated use of
      parenting skills after receiving brief instructions, with more children than not
      trying at least one novel/non-preferred food.

PMID- 30209677
TI  - A matched and controlled longitudinal cohort study of dehydrated human amniotic
      membrane allograft sheet used as a wraparound nerve bundles in robotic-assisted
      laparoscopic radical prostatectomy: a puissant adjunct for enhanced potency
      outcomes.
AB  - We sought to explore the potency outcomes in two systematically controlled, non
      randomized, matched, homogenous patient cohorts, which either underwent
      intervention (INT) with placement of dehydrated human amniotic membrane (dHAM)
      around nerve bundles (NVB) during robotic-assisted laparoscopic radical
      prostatectomy (RALP) or did not (CON). It is hypothesized that dHAM use would
      lead to better potency outcomes. 1400 eligible informed, consented patients
      underwent full bilateral nerve-sparing RALP by a single surgeon, wherein 700
      patients had dHAM allograft wrapped around the NVB and 700 did not. Groups were
      matched demographically, clinically, and biochemically. Potency was defined as
      the ability to have satisfactory penetrative intercourse > 50% of time with SHIM
      score of >= 17 with or without of phosphodiesterase-5 inhibitors. A retrospective
      matched longitudinal cohort study was performed at 1 year. The first noticeable
      erection sufficient enough for a satisfactory penetrative intercourse was
      significantly earlier (p < 0.01; 34.6 +/- 3.6 days), whereas the decrease in SHIM
      score was lower (4.27 +/- 0.14 days) in INT. Binary logistic regression
      demonstrated that INT was an independent significant (p < 0.001) predictor of
      achieving potency at 1 year, such that INT was 3.86 times (95% CI 2.43-6.13) more
      likely to achieve potency in the same period when compared with CON. Chi square
      analysis demonstrated that recovery of potency in INT was better (p < 0.05) in
      every quarter compared to CON. A higher (p < 0.005) percentage (93.1%) of INT
      regained potency versus CON (87.1%) at 1 year.

PMID- 30209676
TI  - Endoscopic Ultrasound-Guided Management of Pain in Chronic Pancreatitis and
      Pancreatic Cancer: an Update.
AB  - OPINION STATEMENT: PURPOSE OF REVIEW: Unrelenting pain from chronic pancreatitis
      (CP) and pancreatic cancer (PC) remain clinical challenges for the physician and
      a significant cause of decreased quality of life for the patient. Endoscopic
      ultrasound (EUS)-guided therapy for each condition is distinct and builds on the
      endosonographer's straightforward access to the celiac axis. RECENT FINDINGS:
      Over the past 20 years, generally small studies of modest methodology have
      surfaced for both EUS-guided celiac plexus block (CPB) and celiac plexus
      neurolysis (CPN). Our review aims to synthesize, analyze, and update the latest
      literature on the technique, efficacy, and safety of these procedures. EUS-CPB's
      role in treating CP pain is likely still relevant for a subset of patients and
      studies have shown efficacy and safety. However, a dramatic drop in research
      publications on the topic will make optimizing its role (including technique,
      injectate, and patient selection) increasingly difficult. However, EUS-CPN for PC
      pain is actively being refined with new information, data, and even guidelines.
      New EUS-guided strategies to treat PC pain besides conventional neurolysis are
      also likely to evolve in coming years.

PMID- 30209678
TI  - Robot-assisted esophageal surgery using the da Vinci(r) Xi system: operative
      technique and initial experiences.
AB  - In this review, we would like to illustrate our experience with the da Vinci(r)
      Xi system in case of esophageal surgery. Since the da Vinci(r) Xi system was
      installed in our department, it has resulted in a great improvement in cases of
      minimally invasive surgery. After the successful establishment in the field of
      colorectal surgery, the next step was surgery of the upper gastrointestinal
      tract. Due to the features of the robotic system, we can definitely observe the
      advantages and a positive effect in case of minimal invasive esophagectomy (MIE).
      We have also tried to develop an adequate surgical standard of the robotic
      assisted minimal invasive esophagectomy with the da Vinci(r) Xi.

PMID- 30209679
TI  - Roles of intestinal microbiota in response to cancer immunotherapy.
AB  - Cancer immunotherapy has been significantly effective on multiple cancers;
      however, there are still a distinct number of non-responding patients and various
      immune-related adverse events in responding patients. It is known that
      heterogeneity of intestinal microbiota may lead to different outcomes of therapy.
      Previous studies have reported that intestinal microbiota is probably attributed
      to influence the efficacy of cancer immunotherapy. Some intestinal bacteria could
      synergize with immune checkpoint blockade agents and optimize the immune response
      against multiple cancers. Therefore, understanding the roles of intestinal
      microbiota could help to improve the clinical efficacy of cancer immunotherapy.
      In this review, we first introduced the close relationships between intestinal
      microbiota and intestinal immune system. Then, we described the emerging
      evidences that intestinal microbiota responses to cancer immunotherapy. Finally,
      we briefly reviewed the technical development on intestinal microbiota research.

PMID- 30209680
TI  - pH-Promoted Release of a Novel Anti-Tumour Peptide by "Stealth" Liposomes: Effect
      of Nanocarriers on the Drug Activity in Cis-Platinum Resistant Cancer Cells.
AB  - PURPOSE: To evaluate the potential effects of PEGylated pH-sensitive liposomes on
      the intracellular activity of a new peptide recently characterized as a novel
      inhibitor of the human thymidylate synthase (hTS) over-expressed in many drug
      resistant human cancer cell lines. METHODS: Peptide-loaded pH-sensitive PEGylated
      (PpHL) and non-PEGylated liposomes (nPpHL) were carefully characterized and
      delivered to cis-platinum resistant ovarian cancer C13* cells; the influence of
      the PpHL on the drug intracellular activity was investigated by the Western Blot
      analysis of proteins involved in the pathway affected by hTS inhibition. RESULTS:
      Although PpHL and nPpHL showed different sizes, surface hydrophilicities and
      serum stabilities, both carriers entrapped the drug efficiently and stably
      demonstrating a pH dependent release; moreover, the different behavior against
      J774 macrophage cells confirmed the ability of PEGylation in protecting liposomes
      from the reticuloendothelial system. Comparable effects were instead observed
      against C13* cells and biochemical data by immunoblot analysis indicated that
      PEGylated pH-sensitive liposomes do not modify the proteomic profile of the
      cells, fully preserving the activity of the biomolecule. CONCLUSION: PpHL can be
      considered as efficient delivery systems for the new promising anti-cancer
      peptide.

PMID- 30209682
TI  - Effects of etidronate, NaOCl, EDTA irrigation solutions and their combinations on
      cyclic fatigue resistance of nickel-titanium single-file rotary and reciprocating
      instruments at body temperature.
AB  - The aim of the present study was to compare the effect of etidronic acid (HEBP),
      NaOCl, and EDTA solutions and their combinations on cyclic fatigue resistance of
      NiTi RPC Blue (RPC Blue), HyFlex EDM (HEDM), and WaveOne Gold (WOG) instruments
      having different metallurgic characteristics at the body temperature (37  degrees
      C). 100 WOG, 100 RPC Blue, and 100 HEDM NiTi files were randomly divided into 5
      groups and immersed in the following solutions: group 1, distilled water; group
      2, 6% NaOCl; group 3, 17% EDTA; group 4, 18% HEBP; group 5, 6% NaOCl and 18%
      HEBP. Then the instruments were rotated in an artificial canal until fracture
      occurred and the number of cycles to fracture was calculated. A univariate
      analysis of variance and post hoc Tukey tests were then performed for comparisons
      using SPSS 21.0 software with the significance level set at P < .05. In all the
      conditions, there was no difference between the cyclic fatigue resistance of WOG
      and RPC Blue files (P > .05). In the intragroup comparison, WOG, RPC Blue, and
      HEDM files showed significantly low cyclic fatigue resistance in group 5 compared
      to other groups (P < .05). Among the groups, there was no statistically
      significant difference in the fracture lengths (P > .05). EDTA, NaOCl and HEBP
      solutions did not affect the cyclic fatigue resistance of the tested files when
      used without combination. However, the combination of NaOCl and HEBP solutions
      significantly reduced the cyclic fatigue resistance of the tested files.

PMID- 30209681
TI  - Survivorship care planning in gynecologic oncology-perspectives from patients,
      caregivers, and health care providers.
AB  - PURPOSE: This qualitative study sought to describe the challenges following
      treatment and the preferences regarding survivorship care among patients treated
      for gynecological cancer, their caregivers, and health care providers. METHODS:
      Between July and August 2017, in-depth semi-structured interviews regarding
      survivorship were conducted at a large academic hospital in the USA among
      patients who recently completed treatment (< 12 months) for a gynecological
      cancer (ovarian, endometrial, cervical, and vulvar) and their primary caregivers.
      A focus group was conducted among health care providers (oncologists, nurses, and
      fellows). Main themes were identified using descriptive content analysis.
      RESULTS: A total of 30 individuals participated in this study (13 patients, 9
      caregivers, 8 health care providers). Almost all participants reported a desire
      for more information on how to address survivorship needs, specifically as they
      related to side effects, follow-up schedule, and psychological assistance.
      Despite this uniformly identified need for more information, preferences for
      survivorship care planning differed across cancer types and individuals, with
      respect to content, timing, and mode of delivery. Health care providers expressed
      challenges in communicating with patients about survivorship, a desire to shift
      post-treatment conversations to the goal of improving quality of life as opposed
      to focusing on disease recurrence, and an unmet need for disease specific and
      individualized survivorship care planning. CONCLUSIONS: Patients, caregivers, and
      health care providers each expressed a need for gynecologic cancer-tailored
      survivorship care resources. IMPLICATIONS FOR CANCER SURVIVORS: The variation of
      disease types and patient and caregiver needs may require multi-faceted,
      individualized survivorship care planning.

PMID- 30209683
TI  - Type D Personality as a Risk Factor in Coronary Heart Disease: a Review of
      Current Evidence.
AB  - PURPOSE OF THE REVIEW: This review article synthesizes recent research findings
      on the psychological context of Type D personality and the mechanisms through
      which Type D affects disease progression and prognosis among patients with
      coronary heart disease (CHD). RECENT FINDINGS: One in four patients with CHD has
      a Distressed (Type D) personality, which is characterized by two stable traits:
      social inhibition and negative affectivity. Type D personality predicts increased
      mortality and morbidity burden, and poorer health-related quality of life. Type D
      is part of a family of psychosocial risk factors that affect CHD prognosis. The
      pattern of co-occurrence of these psychosocial factors and intra-individual
      differences in psychosocial profiles may affect risk prediction accuracy.
      Multiple biological and behavioral processes have been associated with Type D
      personality. Identifying pathways explaining the observed associations between
      Type D personality and CHD is important to improve etiological and
      pathophysiological knowledge and to design personalized interventions, and
      targeting specific risk-associated pathways.

PMID- 30209685
TI  - SOX3 can promote the malignant behavior of glioblastoma cells.
AB  - PURPOSE: Glioblastoma is the most common and lethal adult brain tumor. Despite
      current therapeutic strategies, including surgery, radiation and chemotherapy,
      the median survival of glioblastoma patients is 15 months. The development of
      this tumor depends on a sub-population of glioblastoma stem cells governing tumor
      propagation and therapy resistance. SOX3 plays a role in both normal neural
      development and carcinogenesis. However, little is known about its role in
      glioblastoma. Thus, the aim of this work was to elucidate the role of SOX3 in
      glioblastoma. METHODS: SOX3 expression was assessed using real-time quantitative
      PCR (RT-qPCR), Western blotting and immunohistochemistry. MTT,
      immunocytochemistry and Transwell assays were used to evaluate the effects of
      exogenous SOX3 overexpression on the viability, proliferation, migration and
      invasion of glioblastoma cells, respectively. The expression of Hedgehog
      signaling pathway components and autophagy markers was assessed using RT-qPCR and
      Western blot analyses, respectively. RESULTS: Higher levels of SOX3 expression
      were detected in a subset of primary glioblastoma samples compared to those in
      non-tumoral brain tissues. Exogenous overexpression of this gene was found to
      increase the proliferation, viability, migration and invasion of glioblastoma
      cells. We also found that SOX3 up-regulation was accompanied by an enhanced
      activity of the Hedgehog signaling pathway and by suppression of autophagy in
      glioblastoma cells. Additionally, we found that SOX3 expression was elevated in
      patient-derived glioblastoma stem cells, as well as in oncospheres derived from
      glioblastoma cell lines, compared to their differentiated counterparts, implying
      that SOX3 expression is associated with the undifferentiated state of
      glioblastoma cells. CONCLUSION: From our data we conclude that SOX3 can promote
      the malignant behavior of glioblastoma cells.

PMID- 30209684
TI  - Overexpression of the Tibetan Plateau annual wild barley (Hordeum spontaneum)
      HsCIPKs enhances rice tolerance to heavy metal toxicities and other abiotic
      stresses.
AB  - BACKGROUND: The calcineurin B-like protein (CBL) and CBL-interacting protein
      kinase (CIPK) signaling system plays a key regulatory role in plant stress
      signaling. The roles of plant-specific CIPKs, essential for CBL-CIPK functions,
      in the response to various abiotic stresses have been extensively studied so far.
      However, until now, the possible roles of the CIPKs in the plant response to
      heavy metal toxicities are largely unknown. RESULTS: In this study, we used
      bioinformatic and molecular strategies to isolate 12 HsCIPK genes in Tibetan
      Plateau annual wild barley (Hordeum spontaneum C. Koch) and subsequently
      identified their functional roles in the response to heavy metal toxicities. The
      results showed that multiple HsCIPKs were transcriptionally regulated by heavy
      metal toxicities (e.g., Hg, Cd, Cr, Pb, and Cu) and other abiotic stresses (e.g.,
      salt, drought, aluminum, low and high temperature, and abscisic acid).
      Furthermore, the ectopic overexpression of each HsCIPK in rice (Oryza sativa L.
      cv Nipponbare) showed that transgenic plants of multiple HsCIPKs displayed
      enhanced tolerance of root growth to heavy metal toxicities (Hg, Cd, Cr, and Cu),
      salt and drought stresses. These results suggest that HsCIPKs are involved in the
      response to heavy metal toxicities and other abiotic stresses. CONCLUSIONS:
      Tibetan Plateau annual wild barley HsCIPKs possess broad applications in
      genetically engineering of rice with tolerance to heavy metal toxicities and
      other abiotic stresses.

PMID- 30209686
TI  - Expression of the RAC1, RHOA and CXCR4 proteins and their interaction as risk
      factors for infiltration to the nipple areola complex in operable breast
      carcinoma.
AB  - BACKGROUND: Nipple areola complex (NAC) infiltration in operable breast carcinoma
      (OBC) is associated with local recurrence. NAC infiltration in OBC suggests that
      RAC1, RHOA and CXCR4 proteins are risk factors for migration and infiltration of
      OBC to NAC. This study aims to analyze the expression and interactions of these
      proteins as risk factors for NAC infiltration in OBC. MATERIALS AND METHODS: This
      is an analytic observational cross-sectional study coupled with a categorical
      comparative study in each 40 subjects of OBC with and without NAC infiltration.
      The immunohistochemistry performed with a cut-off point based on the result of a
      receiver operating characteristics (ROC). RESULTS: RAC1, p < 0.001 with POR 5.76,
      95% CI: 2.06-16.08; RHOA, p < 0.001 with POR 7.00, 95% CI: 2.28-21.53; and CXCR4,
      p = 0.001 with POR 6.33, 95% CI 2.06-19.49. There was an interaction between RAC1
      and RHOA (p < 0.001 with POR 17.14, 95% CI: 3.07-125.66); between RAC1 and CXCR4
      (p < 0.001 with POR 30.93, 95% CI 3.62-686.89); between RHOA and CXCR4 (p < 0.001
      with POR 10.21, 95% CI 2.19-54.17); and between the RAC1, RHOA and CXCR4 proteins
      (p < 0.001 with POR = 23.69, 95% CI 2.51-544.86). CONCLUSION: We conclude that
      the expression of the RAC1, RHOA, and CXCR4 proteins and their interactions play
      a role as risk factors of NAC infiltration.

PMID- 30209688
TI  - Expression of ASIC3 in the Trigeminal Nucleus Caudalis Plays a Role in a Rat
      Model of Recurrent Migraine.
AB  - Acid-sensing ion channel 3 (ASIC3) is abundant in the trigeminal nervous system
      and is most sensitive to a slight pH decrease. Recent studies have indicated that
      ASIC3 in the peripheral trigeminal ganglia is likely involved in the pathogenesis
      of migraine pain. However, it is unclear whether this receptor plays a role in
      recurrent migraine, namely, migraine chronicity. Here, we aimed to investigate
      the role of ASIC3 in an animal model of recurrent migraine (RM). In this study,
      we established a rat model of RM through repeated administration of inflammatory
      soup (IS) onto the dura. Then, we tested the mechanical pain thresholds of the
      face and hindpaws by von Frey filaments. qRT-PCR, Western blot and
      immunofluorescence labelling were used to detect the expression and localization
      of ASIC3 in the trigeminal nucleus caudalis (TNC). The protein levels of
      calcitonin gene-related peptide (CGRP), its receptor component receptor activity
      modifying protein 1 (RAMP1) and c-Fos were analysed following treatment with the
      ASIC3 inhibitor APETx2 and activator 2-guanidine-4-methylquinazoline (GMQ). We
      found decreased pain thresholds after repeated dural inflammatory stimulation,
      which suggested the establishment of an RM model. Based on this model, we
      observed elevated expression of ASIC3 in the TNC group compared to that in the
      Sham group. ASIC3 was primarily expressed in neurons but not in astrocytes of the
      TNC. Moreover, APETx2 attenuated tactile allodynia and significantly decreased
      the expression of c-Fos, CGRP and RAMP1, while GMQ aggravated these effects
      compared to those observed in the IS + vehicle group. These findings indicate a
      critical role of ASIC3 channels in the pathophysiology of RM, and ASIC3 might
      represent a potential therapeutic target to prevent the progression of migraine.

PMID- 30209687
TI  - Do GWAS and studies of heterozygotes for NPC1 and/or NPC2 explain why NPC disease
      cases are so rare?
AB  - Early onset Niemann-Pick C diseases are extremely rare, especially Niemann-Pick
      C2. Perhaps unusually for autosomal recessive diseases, heterozygotes for
      mutations in NPC1 manifest many biological variations. NPC2 deficiency has large
      effects on fertility. These features of NPC1 and NPC2 are reviewed in regard to
      possible negative selection for heterozygotes carrying null and hypomorphic
      alleles.

PMID- 30209690
TI  - Correction to: Publication of Abstracts and Full Papers from the International
      Conference on the Origin of Life, San Diego, 2017.
AB  - Plans for the publication of Abstracts from the meeting have been cancelled.
      However, manuscripts for full papers will still be considered for publication in
      OLEB.

PMID- 30209689
TI  - Clinical and prognostic features of spinal meningioma: a thorough analysis from a
      single neurosurgical center.
AB  - PURPOSE: The aim of this study was to thoroughly analyze the clinical
      characteristics of a large cohort of spinal meningioma (SM) from a single
      neurological center and identify risk factors associated with worse progression
      free survival and neurological function outcome. METHODS: Clinical information
      was retrieved from 483 SM and 9806 cranial meningioma cases who were operated in
      our center between 2003 and 2013. 194 SM patients who were followed at the main
      branch were used for prognostic analyses that included both recurrence free
      survival and neurological functions based on Modified McCormick scale (MMS).
      RESULTS: Females were predominant (P < 0.001). High grade tumors were not common
      (WHO grade II, 2.9%; grade III, 1.7%), while the clear cell subtype was frequent
      within grade II SMs (6/14, 42.9%). Macroscopic total resection was achieved in
      all SMs (Simpson grade I, 30.9%; grade II, 65.5%; grade III, 3.6%) with a low
      complications rate (4.6%) and provided neurological improvement in 80 patients
      (41.2%). Recurrence was seen in 9 cases (4.6%) and associated with high WHO
      grade, male, prior recurrence, and Simpson grade III. High WHO grade and high Ki
      67 index were identified to be independent factors predictive of both
      neurological function deterioration and impaired post-operative neurological
      status. CONCLUSIONS: Our analysis of the largest SM cohort in scale from a single
      institution offers a comprehensive view of the clinical characteristics of
      surgically treated SM, revealing the distinct biology of SM in comparison to its
      cranial counterparts, and providing guidance to improve surgical management of
      SM.

PMID- 30209692
TI  - Is There Still a Role for Digoxin in the Management of Atrial Fibrillation?
AB  - PURPOSE OF REVIEW: A number of recent observational analyses have assessed
      clinical outcomes associated with digoxin use in patients with atrial
      fibrillation. In this review, we review these data and provide suggestions on the
      contemporary use of digoxin in patients with atrial fibrillation as supported by
      the recent evidence. RECENT FINDINGS: Observational data from clinical trials and
      registries have provided variable results on the safety and efficacy of chronic
      digoxin use in patients with atrial fibrillation. In general, results have been
      consistent with an associated increase in adverse clinical outcomes with digoxin
      use in atrial fibrillation patients without heart failure. In atrial fibrillation
      patients with heart failure, while the weight of evidence suggested an associated
      risk with digoxin therapy, the results are inconsistent. In patients with atrial
      fibrillation without heart failure, digoxin should generally be avoided. In
      atrial fibrillation patients with heart failure, digoxin should generally be
      reserved for patients that do not achieve adequate rate control or are not
      tolerant of other rate control therapies.

PMID- 30209694
TI  - Response from the authors re: Letter to the Editor for our manuscript "The cost
      of a euploid embryo identified from preimplantation genetic testing for
      aneuploidy (PGT-A): a counseling tool".

PMID- 30209691
TI  - An update on inflammatory choroidal neovascularization: epidemiology, multimodal
      imaging, and management.
AB  - Inflammatory choroidal neovascular membranes are challenging to diagnose and
      manage. A number of uveitic entities may be complicated by the development of
      choroidal neovascularization leading to a decrease in central visual acuity. In
      conditions such as punctate inner choroidopathy, development of choroidal
      neovascularization is extremely common and must be suspected in all cases. On the
      other hand, in patients with conditions such as serpiginous choroiditis, and
      multifocal choroiditis, it may be difficult to differentiate between inflammatory
      choroiditis lesions and choroidal neovascularization. Multimodal imaging
      analysis, including the recently introduced technology of optical coherence
      tomography angiography, greatly aid in the diagnosis and management of
      inflammatory choroidal neovascularization. Management of these neovascular
      membranes consists of anti-vascular growth factor agents, with or without
      concomitant anti-inflammatory and/or corticosteroid therapy.

PMID- 30209695
TI  - Risk of adverse outcomes in patients with rheumatoid arthritis hospitalized for
      stroke-a cross-sectional study.
AB  - Specific data regarding the full range of stroke outcomes among patients with
      rheumatoid arthritis (RA) are lacking. This study aimed to investigate outcomes
      in RA patients hospitalized for a stroke. The study retrieved data from the
      Taiwan Longitudinal Health Insurance Database 2005. We identified 26,336 patients
      who were hospitalized for stroke treatment. Of these patients, 736 patients with
      a prior diagnosis of RA before the index hospitalization were selected as the
      study group. We selected 2208 age-sex-matched patients without RA as the
      comparison group. We performed conditional logistic regressions to calculate odds
      ratios (ORs) for in-hospital mortality and secondary diagnoses of pneumonia,
      urinary tract infections (UTIs), peptic ulcers, acute respiratory failure, and
      the use of mechanical ventilation to compare RA patients and comparison patients.
      We also compared the length of stay (LOS) and hospitalization costs between
      patients with RA and comparison patients. We found that RA patients had a
      significantly increased risk of peptic ulcer during the stroke hospitalization
      (OR = 1.52, 95% CI = 1.05-2.20). However, there were no significant differences
      between patients with RA and comparison patients in terms of in-hospital
      mortality, pneumonia, UTIs, acute respiratory failure, or the use of mechanical
      ventilation. Furthermore, the LOS of stroke hospitalization did not differ
      between the two groups. We concluded that RA patients hospitalized for a stroke
      do not have a significantly different risk of in-hospital mortality, pneumonia,
      UTIs, and mechanical ventilator use, but they have a higher risk of peptic
      ulcers. Additionally, among patients with a subarachnoid/intracerebral
      hemorrhagic stroke, RA patients were more likely to have received mechanical
      ventilation than comparison patients (adjusted OR = 1.89, 95% CI = 1.14-3.15).

PMID- 30209697
TI  - Association between epilepsy and headache.
AB  - OBJECTIVE: Similar clinical characteristics of epilepsy and migraine and the
      prevalence of their comorbidity have been investigated for years. The present
      study investigated the relationship between epilepsy and headache. METHODS: A
      total of 420 epilepsy patients, who visited epilepsy outpatient clinic within 6
      month period between January 2016 and June 2016, were questioned whether they
      have headache. Age, gender, duration of epilepsy, type of seizures, and temporal
      relationship of headache with seizure were investigated in the patients with
      headache. RESULTS: Headache was detected in 111 (26%) of 420 epilepsy patients.
      The prevalence of migraine was 15%. When the temporal relationship of headache
      with seizure was evaluated, interictal headache was found to be the most common
      type with a percentage of 74.8%. No significant difference was determined between
      the patients with migraine and non-migraine headache in terms of age, gender,
      duration of epilepsy, age at the onset of epilepsy, type of seizure, and
      electroencephalography findings. The prevalence of interictal headache was
      statistically significantly higher in migraine patients as compared to that of
      non-migraine patients (p < 0.001); however, the prevalence of preictal headache
      and the prevalence of postictal headache were significantly lower (p = 0.001 and
      p < 0.001, respectively). CONCLUSION: The prevalence of headache and the
      prevalence of migraine, which are considered to be pathogenetically linked to
      epilepsy, were not different in epilepsy patients as compared to that of the
      general population. Different outcomes and percentages in other studies suggest
      that pathogenesis of headache is multifactorial and that different diagnostic
      criteria might have been taken into consideration.

PMID- 30209693
TI  - Additive Manufacturing with 3D Printing: Progress from Bench to Bedside.
AB  - Three-dimensional (3D) printing was discovered in the 1980s, and many industries
      have embraced it, but the pharmaceutical industry is slow or reluctant to adopt
      it. Spiritam(r) is the first and only 3D-printed drug product approved by FDA in
      2015. Since then, the FDA has not approved any 3D-printed drug product due to
      technical and regulatory issues. The 3D printing process cannot compete with well
      established and understood conventional processes for making solid dosage forms.
      However, pharmaceutical companies can utilize it where mass production is not
      required; rather, consistency, precision, and accuracy in quality are paramount.
      There are many 3D printing technologies available, and not all of them are
      amenable to pharmaceutical manufacturing. Each 3D technology has certain
      prerequisites in terms of material that it can handle. Some of the pertinent
      technical and regulatory issues are as follows: Current Good Manufacturing
      Practice, in-process tests and process control, and cleaning validation. Other
      promising area of 3D printing use is printing medications for patients with
      special needs in a hospital and/or pharmacy setting with minimum regulatory
      oversight. This technology provides a novel opportunity for in-hospital
      compounding of necessary medicines to support patient-specific medications.
      However, aspects of the manufacturing challenges and quality control
      considerations associated with the varying formulation and processing methods
      need to be fully understood before 3D printing can emerge as a therapeutic tool.
      With these points in mind, this review paper focuses on 3D technologies amenable
      for pharmaceutical manufacturing, excipient requirement, process understanding,
      and technical and regulatory challenges.

PMID- 30209698
TI  - A novel homozygous GALC variant has been associated with Krabbe disease in a
      consanguineous family.
AB  - Krabbe disease (KD) or globoid cell leukodystrophy is an autosomal recessive
      lysosomal storage disorder involving the white matter of the peripheral and the
      central nervous systems. It is caused by a deficiency of galactocerebrosidase
      enzyme activity. The most common manifestation is the classical early onset KD
      that leads to patient's loss before the age of 2. Herein, we report the
      evaluation of a consanguineous family with three affected children manifesting
      severe neurological findings that ended with death before the age of 2, in an
      attempt to provide genetic diagnosis to the family. One of the children underwent
      detailed physical and neurological examinations, including brain magnetic
      resonance imaging (MRI) and scalp electroencephalography (EEG) evaluations. GALC
      genetic testing on this child enabled identification of a novel homozygous
      variant (NM_000153.3: c.1394C>T; p.(Thr465Ile)), which confirmed diagnosis as KD.
      Familial segregation of this variant was performed by PCR amplification and
      Sanger sequencing that revealed the parents as heterozygous carriers. We believe
      this novel GALC variant will not only help in genetic counseling to this family
      but will also aid in identification of future KD cases.

PMID- 30209696
TI  - Comparison of the construct validity and reproducibility of four different types
      of patient-reported outcome measures (PROMs) in patients with rheumatoid
      arthritis.
AB  - Patient-reported outcome measures (PROMs) are increasingly used in the assessment
      of patients with rheumatoid arthritis (RA). The aim of this study was to assess
      the construct validity and reproducibility of four types of PROMs (numerical
      rating scale (NRS), visual analogue scale (VAS), verbal rating scale (VRS), and
      Likert scale). In addition, patients' preference for one of these PROMs was
      measured. Patients with stable RA and no change in pain medication or steroid
      medication (n = 211) were asked to complete a questionnaire directly following,
      and 5 days after their outpatient visit. The questionnaire measured the validity
      of the PROMs in four domains (pain, fatigue, experienced disease activity, and
      general well-being). To assess construct validity, Pearson correlation
      coefficients were calculated using the Disease Activity Score-3. To assess
      reproducibility, intraclass correlation coefficients (ICCs) were calculated.
      Correlation coefficients between the different PROMs within each domain were
      compared. There were no differences regarding construct validity between the
      different PROM scale types. Regarding reproducibility, VAS and NRS scored better
      in the domains pain and experienced disease activity. Patients chose NRS as
      preferred measurement method, with the VAS in second place. The four scale types
      of PROMs appeared to be equally valid to assess pain, fatigue, experienced
      disease activity, and general well-being. VAS and NRS appeared to be more
      reliable for measuring pain and experienced disease activity. The patients
      favoured NRS. In combination with other practical advantages of NRS over VAS, we
      do advise the NRS as the preferred scale type for PROMs.

PMID- 30209699
TI  - The performance of patients with Parkinson's disease on the Face-Name Associative
      Memory Examination.
AB  - In this study, we examined the performance of patients with Parkinson's disease
      (PD) with different cognitive profiles on the Face-Name Associative Memory
      Examination (FNAME). We evaluated 71 patients with a comprehensive
      neuropsychological battery. The results revealed that the group with executive
      and additional visuospatial deficits demonstrated significantly lower scores on
      FNAME. This finding indicates the possible clinical utility of FNAME for
      screening patients with PD with distinct cognitive profiles. Further longitudinal
      studies are needed to consider the prognostic adequacy of FNAME in detecting high
      risk Parkinson's disease dementia (PDD).

PMID- 30209700
TI  - Six-year clinical and MRI quantitative susceptibility mapping (QSM) follow-up in
      neurological Wilson's disease under zinc therapy: a case report.

PMID- 30209701
TI  - Ivosidenib: First Global Approval.
AB  - Ivosidenib (Tibsovo(r)) is a small molecule, orally available inhibitor of
      mutated cytosolic isocitrate dehydrogenase 1 (IDH1) that is being developed by
      Agios Pharmaceuticals for the treatment of cancer in patients with IDH1
      mutations. The mutated form of the IDH1 enzyme produces a metabolite, 2
      hydroxyglutarate (2-HG), which is thought to play a role in the formation and
      progression of acute myeloid leukaemia (AML), gliomas and other cancers. Elevated
      2-HG levels interfere with cellular metabolism and epigenetic regulation, thereby
      contributing to oncogenesis. Ivosidenib targets the IDH1 metabolic pathway to
      prevent a build-up of the oncometabolite 2-HG. This article summarizes the
      milestones in the development of ivosidenib leading to this first approval in the
      USA for the treatment of patients with relapsed or refractory AML with a
      susceptible IDH1 mutation. Clinical development for AML, cholangiocarcinoma,
      glioma, myelodysplastic syndromes and solid tumours is ongoing worldwide.

PMID- 30209702
TI  - Autonomic symptom burden is an independent contributor to multiple sclerosis
      related fatigue.
AB  - OBJECTIVES: To investigate a possible association between autonomic dysfunction
      and fatigue in people with multiple sclerosis. METHODS: In 70 people with
      multiple sclerosis early in the disease course (51 females, mean age 33.8 +/-
      9.1), quantitative sudomotor axon reflex tests, cardiovascular reflex tests
      (heart rate and blood pressure responses to the Valsalva maneuver and heart rate
      response to deep breathing), and the tilt table test were performed. Participants
      completed the Composite Autonomic Symptom Score 31, the Modified Fatigue Impact
      Scale, and the Epworth Sleepiness Scale, as well as the Beck Depression
      Inventory. Cutoff scores of >= 38 or >= 45 on the Modified Fatigue Impact Scale
      were used to stratify patients into a fatigued subgroup (N = 17 or N = 9,
      respectively). RESULTS: We found clear associations between fatigue and scores in
      subjective tests of the autonomic nervous system: fatigued patients scored
      significantly worse on Composite Autonomic Symptom Score 31, and there was a
      strong correlation between the Modified Fatigue Impact Scale and the Composite
      Autonomic Symptom Score 31 (rs = 0.607, p < 0.001). On the other hand, we found
      only modest associations between fatigue and scores in objective tests of the
      autonomic nervous system: there was a clear trend for lower sweating outputs at
      all measured sites, which reached statistical significance for the distal leg and
      foot. We found weak correlations between the Modified Fatigue Impact Scale and
      the Valsalva ratio (rs = - 0.306, p = 0.011), as well as between the Modified
      Fatigue Impact Scale and quantitative sudomotor axon reflex tests of the forearm,
      proximal, and distal lower leg (rs = - 0.379, p = 0.003; rs = - 0.356, p = 0.005;
      and rs = - 0.345, p = 0.006, respectively). A multiple regression model showed
      that the Composite Autonomic Symptom Score 31, Beck Depression Inventory, and
      Epworth Sleepiness Scale were independent predictors of fatigue (p = 0.005, p =
      0.019, and p = 0.010, respectively). CONCLUSION: These results suggest that-even
      early in the course of the disease-people with multiple sclerosis suffer from
      objective and subjective impairments of the autonomic nervous system. The results
      also point to an association between autonomic nervous system impairment and
      multiple sclerosis related fatigue.

PMID- 30209703
TI  - Evidence-Based Treatment Strategies in Youth Mental Health Services: Results from
      a National Survey of Providers.
AB  - Previous surveys indicate infrequent use of evidence-based treatment (EBT)
      manuals in usual care youth mental health, but the extent to which providers use
      core and common EBT strategies and what contextual factors impact EBT strategy
      implementation need further study. In a national, multidisciplinary survey of
      1092 youth-serving providers, providers reported regular use of many EBT
      strategies. Provider learning theory orientation, more recent degree, more
      standardized and ongoing assessment use, more positive attitudes toward
      innovation and evidence, fewer low-income clients, and perceptions that their
      agency valued quality care and provided fewer training resources predicted more
      frequent EBT strategy use.

PMID- 30209704
TI  - Modeling of a single nanoparticle interaction with the human blood plasma
      proteins.
AB  - When nanoparticles are introduced into a physiological environment, proteins and
      lipids immediately cover their surface, forming a protein "corona". It is well
      recognized that the corona structure influences the biological response of the
      body. Two deterministic models for corona formation of the human blood serum
      proteins around a single nanoparticle are presented and studied numerically in
      this paper. One of them is based on a coupled system of PDEs and involves
      diffusion of proteins toward the nanoparticle surface. The other one is described
      by ODEs and is a limit version of the first model as the protein diffusivity
      tends to infinity. The protein diffusivity influence on the temporal corona
      structure is studied in detail. Results are presented using figures and
      discussion.

PMID- 30209705
TI  - Medical Robotics.

PMID- 30209706
TI  - Reduction of Pressure Gradient and Turbulence Using Vortex Generators in
      Prosthetic Heart Valves.
AB  - Blood damage and platelet activation are inherent problems with present day bi
      leaflet mechanical heart valve designs. Passive flow control through different
      arrangements of vortex generators (VG) as means of improving pressure gradients
      and reducing turbulence are investigated. Rectangular VG arrays were mounted on
      the downstream surfaces of a 23 mm 3D printed mechanical valve. The effect of VGs
      on the resulting flow structures were assessed under pulsatile physiological flow
      conditions where high resolution particle image velocimetry measurement was
      performed. The co-rotating VGs showed lower Reynolds shear stresses and improved
      pressure gradients (PG) compared with the counter-rotating ones and the no-VG
      control one (that showed higher turbulence). RSS was found 38.13 +/- 0.89, 12.95
      +/- 0.32, 15.75 +/- 0.71, 24.54 +/- 0.84 and 16.33 +/- 0.58 Pa for the control,
      co-rotating VGs, 8 counter-rotating VGs, 4 far-spaced VGs and 4 closely-spaced
      VGs, respectively. PG of 10.45 +/- 0.94 mmHg was obtained with co-rotating VGs
      and the difference was significant compared with the other configurations
      (control 14.88 +/- 0.4 mmHg; 8 counter-rotating VGs 13.76 +/- 0.51 mmHg; 4 far
      spaced VGs 13.84 +/- 0.09 mmHg; and 4 closely-spaced VGs 15.37 +/- 0.16 mmHg). Co
      rotating VGs for this application induce a more delayed flow separation and a
      more homogenized and streamlined transition of flow compared with the counter
      rotating VGs. Passive flow control techniques deployed on BHMVs is potentially
      beneficial as significant control of flow at small length scales without inducing
      large-scale design modifications of the valve.

PMID- 30209707
TI  - Identification and expression analysis of genes with pathogen-inducible cis
      regulatory elements in the promoter regions in Oryza sativa.
AB  - BACKGROUND: Complex co-regulatory networks in plants may elicit responses during
      pathogen infections. A number of genes are activated when these responses take
      place. Identification of these genes would shed new light on understanding the
      mechanisms of rice response to pathogen infections and the elucidation of
      crosstalk among diverse signaling networks in rice disease
      resistance/susceptibility. RESULTS: Here we report the identification of genes
      with pathogen-inducible cis-regulatory elements (PICEs) (AS-1, G-box, GCC-box,
      and H-box) in the promoter regions in rice. Our results showed that a set of 882
      rice genes contained these four elements in their promoter regions. Of these
      genes, 190 encode disease resistance/susceptibility related proteins, and 70
      encode transcription factors. Analyses of the available microarray data
      demonstrated that 357 transcripts were differentially expressed after pathogen
      infections. 48 out of 53 differentially expressed transcription factors are up
      regulated or down-regulated by more than 1.1-fold in response to pathogen
      infections. Analyses of the public mRNA-Seq data showed that 327 transcripts were
      differently expressed after pathogen infections. A total of 100 up-regulated
      genes and 37 down-regulated genes were found in common between the microarray and
      mRNA-Seq data. CONCLUSIONS: We report here a set of rice genes that contain the
      four PICEs, i.e., AS-1, G-box, GCC-box, and H-box, in their promoter regions, of
      which, 53.5% were up- or down-regulated when pathogens attack. The PICEs in the
      gene promoters are critical for rice response to pathogen infections. They are
      also useful markers for identification of rice genes involved in response to
      pathogen infections.

PMID- 30209709
TI  - Gender-Typed Personality Qualities and African American Youth's School
      Functioning.
AB  - Numerous studies document sex differences in African American girls' and boys'
      academic achievement and motivation, but little is known about how the enactment
      of gender, such as in the forms of gendered behaviors, attitudes, or personal
      social qualities, is related to school functioning. To advance understanding of
      African American adolescents' academic experiences, this study examined the
      longitudinal linkages between stereotypically feminine (i.e., expressive) and
      stereotypically masculine (i.e., instrumental) personality characteristics and
      school adjustment. The moderating effects of youth's ethnic identity and school
      racial composition also were tested. Participants were 352 African American youth
      (50.1% girls; mean age at Time 1 = 12.04 years; SD = 2.03) who participated in
      annual home interviews. Net of biological sex, expressive traits (kind,
      sensitive) were positively related to school self-esteem and school bonding for
      both girls and boys, but youth with higher levels of instrumentality
      (independent, competitive) exhibited sharper declines in academic achievement
      across adolescence. School racial composition moderated the effects of
      instrumentality at the between-person level, such that instrumentality was
      positively related to school self-esteem only for youth who attended schools with
      fewer African American students. These results highlight the importance of
      incorporating gendered personality traits, rather than biological sex alone, into
      theoretical accounts of African American youth's school functioning.

PMID- 30209708
TI  - Calprotectin and cross-linked N-telopeptides of type I collagen levels in
      crevicular fluid from implant sites with peri-implant diseases: a pilot study.
AB  - BACKGROUND: Peri-implant crevicular fluid (PICF) contains calprotectin and NTx,
      which are markers for inflammation and bone resorption, respectively. The aims of
      this pilot study were to compare calprotectin and NTx levels in PICF from implant
      sites with or without peri-implant diseases and to evaluate the usefulness of
      calprotectin and NTx as diagnostic markers for peri-implant diseases. METHODS:
      Thirty-five patients with dental implants participated in this pilot study. PICF
      samples were collected from peri-implant disease sites (n = 40) and non-diseased
      (healthy) sites (n = 34) after clinical indicators including probing depth (PD),
      bleeding on probing (BOP), gingival index (GI), and bone loss (BL) rate were
      investigated. Calprotectin and NTx amounts in PICF were measured using their
      respective ELISA kits and then compared between diseased and healthy samples. The
      relationship between PICF calprotectin or NTx levels and clinical indicator
      levels was investigated. A receiver operating characteristic (ROC) curve analysis
      of calprotectin and NTx was performed to predict peri-implant diseases. RESULTS:
      Calprotectin and NTx levels in PICF were significantly higher from peri-implant
      disease sites than from healthy sites. PICF calprotectin amounts correlated with
      PD, and its levels were significantly higher in the GI-1 and GI-2 groups than in
      the GI-0 group. PICF NTx amounts correlated with PD and the BL rate. ROC curves
      indicated that PICF calprotectin and NTx are useful biomarkers for peri-implant
      diseases. CONCLUSIONS: Calprotectin and NTx in PICF have potential as biomarkers
      for the diagnosis of peri-implant diseases.

PMID- 30209710
TI  - The Influence of Economic Pressure on Emerging Adult Binge Drinking: Testing the
      Family Stress Model over Time.
AB  - The Family Stress Model proposes that disrupted family processes may help explain
      the association between economic adversity and poor child developmental outcomes.
      In this study, the Family Stress Model was tested across adolescence to emerging
      adulthood. Participants included 451 rural White youth who participated with
      their parents from age 13-23 (52% female). The data were analyzed at five
      developmental time periods with separate pathways for mothers and fathers. The
      findings reveal for both parents that economic pressure at time 1 (age 13) led to
      parental emotional distress which was related to harsh couple interaction at time
      2 (ages 14 and 15). This marital conflict was related to harsh parenting toward
      the adolescent (time 2), which was then directly associated with higher levels of
      offspring drinking when youth were in middle adolescence (age 16) at time 3.
      Alcohol use in middle adolescence was associated with binge drinking in late
      adolescence (age 18, time 4) into emerging adulthood (age 23, time 5). Drinking
      behaviors did not differ for boys and girls. The current results show that
      economic adversity has an effect on family processes which influence offspring
      binge drinking patterns in later adolescence that continue into emerging
      adulthood.

PMID- 30209711
TI  - Michaelis-Menten from an In Vivo Perspective: Open Versus Closed Systems.
AB  - After a century of applications of the seminal Michaelis-Menten equation since
      its advent it is timely to scrutinise its principal parts from an in vivo point
      of view. Thus, the Michaelis-Menten system was revisited in which enzymatic
      turnover, i.e. synthesis and elimination was incorporated. To the best of our
      knowledge, previous studies of the Michaelis-Menten system have been mainly based
      on the assumption that the total pool of enzyme, free and bound, is constant.
      However, in fact this may not always be the case, particularly for chronic
      indications. Chronic (periodic) administration of drugs is often related to
      induction or inhibition of enzymatic processes and even changes in the free
      enzymatic load per se. This may account for the fact that translation of in vitro
      metabolism data have shown to give systematic deviations from experimental in
      vivo data. Interspecies extrapolations of metabolic data are often challenged by
      poor predictability due to insufficient power of applied functions and methods.
      By incorporating enzyme turnover, a more mechanistic expression of substrate,
      free enzyme and substrate-enzyme complex concentrations is derived. In
      particular, it is shown that whereas in closed systems there is a threshold for
      chronic dosing beyond which the substrate concentration keeps rising, in open
      systems involving enzyme turnover this is no longer the case. However, in the
      presence of slow enzyme turnover, after an initial period of adjustment which may
      be quite long, the relation between substrate concentration and dose rate reduces
      to a linear expression. This new open framework is also applicable to transporter
      systems.

PMID- 30209713
TI  - Enhancing Expression of 3-Ketosteroid-9alpha-Hydroxylase Oxygenase, an Enzyme
      with Broad Substrate Range and High Hydroxylation Ability, in Mycobacterium sp.
      LY-1.
AB  - 3-Ketosteroid-9alpha-hydroxylase (KSH) consists of two protein systems, KshA and
      KshB, and is a key enzyme in microbial degradation pathway of natural sterols.
      9alpha-Hydroxy-4-androstene-3,17-dione (9alpha-OH-AD) is a valuable steroid
      pharmaceutical intermediate. The expression of a 3-ketosteroid-9alpha-hydroxylase
      oxygenase (KshA1) with a broad substrate range and high hydroxylation ability was
      enhanced in Mycobacterium sp. LY-1 to improve the yield of 9alpha-OH-AD. Through
      whole-genome sequence mining and homologous comparison, the putative genes (kshA1
      and kshB) in wild strain LY-1 were firstly identified. Then they were
      heterogeneously co-expressed in Escherichia coli BL21. The transformation results
      of recombinant BL21-KshA1/B demonstrated KshA1/B had high hydroxylation ability
      to AD. Moreover, substrate preference analysis suggested that KshA1LY-1 had a
      broad substrate range. After enhancing expression of kshA1 and kshB in the strain
      LY-1, the maximum productivity of 9alpha-OH-AD in recombinant LY-1-KshA1/B
      reached 0.064 g/L/h in a 5-L stirred fermenter.

PMID- 30209714
TI  - Comparison of Two Apnea Test Methods, Oxygen Insufflation and Continuous Positive
      Airway Pressure During Diagnosis of Brain Death: Final Report.
AB  - INTRODUCTION: Deterioration of the pulmonary function after the apnea test (AT)
      conducted with the classic oxygen insufflation AT (I-AT) is often observed during
      the brain death (BD) diagnosis procedure. In the present study, two AT methods
      were compared before a method is recommended for the currently revised Polish BD
      criteria. METHODS: Classic I-AT and continuous positive airway pressure AT (CPAP
      AT) were performed in 60 intensive care unit patients. I-AT was performed at the
      end of two series of clinical tests, and approximately 1-1.5 h later, after BD
      was confirmed, a different method, CPAP-AT with 100% FiO2 and CPAP value of 10 cm
      H2O provided by a ventilator in CPAP mode was performed. The patients in I-AT and
      CPAP-AT groups were further divided into two subgroups: non-hypoxemic (NH) with
      good lung function before AT (PaO2/FiO2 index >= 200 mmHg) and hypoxemic (H) with
      poor lung function (PaO2/FiO2 index < 200 mmHg). PaO2 and PaCO2 were recorded
      prior to I-AT and CPAP-AT at time-point one (T1), 5 min after each test at time
      point two (T2), and after 10 min prior to the end of tests at time-point three
      (T3). The I-AT NH subgroup consisted of 50 patients, and CPAP-AT NH subgroup 43
      patients. The I-AT H subgroup consisted of 10 patients, and the CPAP-AT H
      subgroup 17 patients. RESULTS: In the I-AT NH subgroup, a gradual decrease in
      PaO2/FiO2 was observed throughout the AT but not in the CPAP-AT NH subgroup. The
      PaO2/FiO2 ratio during the AT in the CPAP-AT H group was stable with a slight
      tendency to increase but not in the I-AT H group. During the first 5 min of the
      AT, the mean increase in CO2 was approximately 5 mmHg/min. Most patients in all
      groups met the AT criteria after 5 min of the test. CONCLUSIONS: The results from
      the study show that I-AT may compromise pulmonary function in some cases and is
      one of the reasons for the recommendation of a safer option, CPAP-AT, in the
      currently revised Polish BD criteria. During AT, the mean CO2 increase rate was 5
      mmHg/min, which, in most patients, would allow the test to be completed after
      just 5 min.

PMID- 30209715
TI  - Correction to: Building Behavioral Health Homes: Clinician and Staff Perspectives
      on Creating Integrated Care Teams.
AB  - The Publisher regrets that due to a malfunction in production, there are
      duplications and errors and rogue addresses in the author affiliations of the
      published article. The correct author affiliations are listed below.

PMID- 30209712
TI  - The Effects of Hand Massage on Stress and Agitation Among People with Dementia in
      a Hospital Setting: A Pilot Study.
AB  - Agitation in people with dementia is a growing concern as it causes distress for
      both patients and their nurses and may contribute to relational disorders.
      Previous studies involving patients with dementia living in long-term care
      facilities have reported decreased agitation following massage. The objective of
      this pilot study was to investigate the effect of hand massage on agitation and
      biological markers of stress in patients with dementia hospitalized in an acute
      geriatric psychiatry service. In this randomized controlled trial we included 40
      agitated patients with dementia with an intervention group and a control group.
      The study is designed to test the effect of seven hand massages over three
      continuous weeks on agitation and levels of salivary cortisol (sC) and alpha
      amylase (sAA). Compared to the control group, the intervention group exhibited
      larger increases in sC and sAA at week 1 from before to after the massage, but
      larger decreases at week 2 and 3, with a significant group effect for sAA at week
      2. Agitation scores were not significantly different between the groups but
      tended to decrease more in the intervention group than the control group. This
      study provides first encouraging results suggesting that hand massage might have
      beneficial effects on stress and agitation in hospitalized patients with
      dementia. It also highlights the challenges associated with conducting such
      studies with this complex patient population. Further studies are needed to
      confirm these findings and the benefits of hand massage as part of routine care
      for patients with dementia.

PMID- 30209716
TI  - Implementing Transdiagnostic Cognitive Behavioral Psychotherapy in Adult Public
      Behavioral Health: A Pilot Evaluation of the Feasibility of the Common Elements
      Treatment Approach (CETA).
AB  - Few evidence-based psychotherapies are provided in adult public behavioral health
      (PBH), despite the need for such treatments. The common elements treatment
      approach (CETA) was developed for use by lay providers in low- and middle-income
      countries and may have relevance in PBH given its unique application with
      individuals with multiple diagnoses including PTSD, depression, and anxiety. This
      study utilized data collected as part of the implementation of CETA in 9 PBH
      agencies in Washington State with 58 providers, including a 2-day workshop and 6
      months of consultation. Outcomes included provider-perceived skill in CETA
      delivery, training and consultation completion rates, and perceived
      appropriateness of CETA for clients. Thirty-nine (67%) providers completed
      requirements for training and consultation, and delivered CETA to a total of 56
      clients. Perceived competence in delivering CETA improved over time, as well as
      client symptom scores. CETA shows promise for feasible and effective
      implementation within US-based PBH systems.

PMID- 30209717
TI  - A Transgenic MMTV-Flippase Mouse Line for Molecular Engineering in Mammary Gland
      and Breast Cancer Mouse Models.
AB  - Genetically engineered mouse models have become an indispensable tool for breast
      cancer research. Combination of multiple site-specific recombination systems such
      as Cre/loxP and Flippase (Flp)/Frt allows for engineering of sophisticated, multi
      layered conditional mouse models. Here, we report the generation and
      characterization of a novel transgenic mouse line expressing a mouse codon
      optimized Flp under the control of the mouse mammary tumor virus (MMTV) promoter.
      These mice show robust Flp-mediated recombination in luminal mammary gland and
      breast cancer cells but no Flp activity in non-mammary tissues, with the
      exception of limited activity in salivary glands. These mice provide a unique
      tool for studying mammary gland biology and carcinogenesis in mice.

PMID- 30209718
TI  - Specific effects of neuregulin-1beta on the communication between DRG neurons and
      skeletal muscle cells in vitro.
AB  - The communication between primary afferent neuron and skeletal muscle (SKM) is
      one of the important factors on maintaining the structure and function of SKM
      cells. Neuregulin-1beta (NRG-1beta) signaling is essential for regulating
      synaptic neurotransmission. Here, we established a neuromuscular coculture model
      of dorsal root ganglion (DRG) sensory neurons and SKM cells to explore the nerve
      muscle communication in the presence of exogenous NRG-1beta. The expression of
      three distinct subtypes (TrkA, TrkB, and TrkC) of tyrosine kinase receptors was
      monitored for the phenotypical alterations of the neurons. The aggregation extent
      of acetylcholine receptor (AChR) represents the specific changes of SKM cells
      after NRG-1beta incubation in this neuromuscular coculture model. The results
      showed that NRG-1beta not only enhanced neurite outgrowth of DRG neurons but also
      increased the length and branches of SKM cells. NRG-1beta treatment not only
      induced expression of all the three subtypes of Trk receptors in neurons but also
      promoted AChR aggregation on the surface of SKM cells. The effects of NRG-1beta
      could be blocked by administration of ERK1/2 inhibitor PD98059, PI3K inhibitor
      LY294002, and JAK2 inhibitor AG490, respectively. These data imply that NRG-1beta
      is essential for the nerve-muscle communication by enhancing growth and modifying
      phenotypes of the two different kinds of cells. The specific effects produced by
      NRG-1beta add novel interpretation for nerve-muscle communication between sensory
      neurons and SKM cells.

PMID- 30209719
TI  - In Their Own Words: Clinician Experiences and Challenges in Administering
      Evidence-Based Treatments for PTSD in the Veterans Health Administration.
AB  - The aim of the present study was to increase the understanding of clinician
      experiences with administering two evidence-based psychotherapies (EBPs) for PTSD
      (Cognitive Processing Therapy and Prolonged Exposure therapy) in the Veterans
      Affairs Healthcare System (VA). The study assessed clinician perceptions through
      the use of two, one-hour focus groups and employed a rigorous data analysis
      approach, Consensual Qualitative Research. Clinicians who work in an outpatient
      PTSD clinic at a New England VA, and who routinely administer EPBs for PTSD,
      participated in the study. Results were categorized into seven domains by the
      coding team, including 1) EBP Strengths, 2) EBP Weaknesses, 3) Challenges
      Specific to the Veteran Population, 4) Perceived EBP Effectiveness, 5) Active
      Ingredients for Treating PTSD, 6) Treatment Structure and Process, and 7)
      Suggested Changes/Improvements to EBPs. These domains are discussed in detail,
      with several core ideas falling under each domain. Operational definitions and
      representative quotes are provided. Overall, clinicians provided a balanced
      perspective and identified both strengths and weaknesses of the EBPs for PTSD.
      They identified several challenges in applying these treatments to veteran
      populations, and shared their beliefs about treatment effectiveness, how they use
      these treatments in their clinical practice, and how they would change the
      treatments if given an opportunity to do so. In this way, the study offers a
      small but important step in attempting to address the science-practice gap
      related to EBP for PTSD implementation efforts in the VA.

PMID- 30209720
TI  - Strengthening Community: Older Asian Immigrants' Contributions to New Zealand
      Society.
AB  - This study sought to uncover the process through which older Chinese, Indian and
      Korean immigrants residing in Auckland, New Zealand contribute to, and
      participate in, local community. There is a paucity of literature addressing the
      everyday activities of older Asian immigrants living in New Zealand. The few
      studies that do exist focus solely on one ethnic group with little discussion of
      how community participation occurs. Grounded theory methodology was employed.
      Focus groups and individual interviews with 76 Chinese, Indian or Korean older
      immigrants were recorded, transcribed, translated, and analysed using grounded
      theory methods of dimensional analysis to develop a theory of participation.
      Older Asian immigrants contribute to society through a process of Strengthening
      Community; comprising three perspectives: Advancing Cultural Connectedness,
      Giving Service and Caring for Family. Each perspective is mediated by conditions
      and strategies that facilitate when and how participants engage in their chosen
      activities. Older Asian immigrants are active social contributors to New Zealand
      communities. Although they encounter barriers to participation, they constantly
      seek ways to work individually and in community groups to effectively contribute
      to civic society. In doing so, they take pride in giving back to their host
      country.

PMID- 30209721
TI  - Primary dysmenorrhea with and without premenstrual syndrome: variation in quality
      of life over menstrual phases.
AB  - PURPOSE: The majority of studies on quality of life (QoL) of women with menstrual
      disturbances have not taken menstrual cycle phase into account. We aimed to
      determine the size of changes in QoL score during perimenstrual week compared to
      those during late follicular phase in women suffering from dysmenorrhea with or
      without premenstrual syndrome (PMS) and also to compare the two groups. METHODS:
      In this observational analytical study, participants were selected purposively
      from among single students aged 18-30 years, who were residing at university
      dormitories in Tabriz, Iran, and had moderate or severe dysmenorrhea. They
      reported quality of their life during the past week using the Quality of Life
      Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) at two time
      points, days 3-4 and 11-12, of their menstrual cycle. RESULTS: Among 52
      participants with PMS and 64 without PMS, about half reported severe
      dysmenorrhea. The mean total quality score was significantly lower during
      perimenstrual week than during late follicular phase in both group with PMS [48
      vs 79, mean difference - 31 (95% confidence interval - 37 to - 26)] and group
      without PMS [56 vs 78, - 1 (- 27 to - 18)]. The score was significantly lower in
      the group with PMS than in those without PMS during perimenstrual week [- 8 (- 13
      to - 2)] but not during late follicular phase [2.1 (- 2.9 to 7.0)]. CONCLUSIONS:
      Dysmenorrhea with or without PMS significantly reduces QoL of women during
      perimenstrual week. The QoL is slightly lower in group with PMS during
      perimenstrual week but not during late follicular phase.

PMID- 30209722
TI  - Adapting summary scores for the PROMIS-29 v2.0 for use among older adults with
      multiple chronic conditions.
AB  - PURPOSE: The patient-reported outcomes measurement information system 29-item
      profile (PROMIS-29 v2.0) is a widely used health-related quality of life (HRQoL)
      measure. Summary scores for physical and mental HRQoL have recently been
      developed for the PROMIS-29 using a general population. Our purpose was to adapt
      these summary scores to a population of older adults with multiple chronic
      conditions. METHODS: We collected the PROMIS-29 v2.0 for 1359 primary care
      patients age 65+ with at least 2 of 13 chronic conditions. PROMIS-29 has 7
      domains, plus a single-item pain intensity scale. We used exploratory factor
      analysis (EFA), followed by confirmatory factor analysis (CFA), to examine the
      number of factors that best captured these eight scores. We used previous results
      from a recent study by Hays et al. (Qual Life Res 27:1885-1891, 2018) to
      standardize scoring coefficients, normed to the general population. RESULTS: The
      mean age was 80.7, and 67% of participants were age 80 or older. Our results
      indicated a 2-factor solution, with these factors representing physical and
      mental HRQoL, respectively. We call these factors the physical health score (PHS)
      and the mental health score (MHS). We normed these summary scores to the general
      US population. The mean MHS for our population of was 50.1, similar to the US
      population, while the mean PHS was 42.2, almost a full standard deviation below
      the US population. CONCLUSIONS: We describe the adaptation of physical and mental
      health summary scores of the PROMIS-29 for use with a population of older adults
      with multiple chronic conditions.

PMID- 30209723
TI  - More than health: quality of life trajectories among older adults-findings from
      The Irish Longitudinal Study of Ageing (TILDA).
AB  - PURPOSE: To test whether ill-health is associated with a decrease in quality of
      life (QoL) over time and if positive social circumstances are beneficial to QoL,
      using the shorter form CASP-12 in a sample drawn from a nationally representative
      cohort of older adults. To do so, the association between factors from a number
      of life domains and QoL was investigated. METHODS: Data were from the first three
      waves of The Irish Longitudinal Study on Ageing, a prospective nationally
      representative study of community dwelling older adults in the Republic of
      Ireland. QoL was measured using the shorter form CASP-12 and the latent growth
      curve method was used to describe within- and between-person variation in
      longitudinal QoL trajectories. RESULTS: There was considerable variation in QoL
      scores cross-sectionally and longitudinally. QoL did not decline linearly with
      age but increased from age 50 and peaked at 68 years before declining in older
      age. QoL differed significantly between individuals and decreased over time. A
      variety of demographic, health, and social characteristics were associated with
      changes in QoL over time. These included cohabiting; self-rated health;
      functional limitations; fear of falling; mental health; loneliness; social
      networks; social activities; caring for grandchildren; income; and death of a
      spouse. CONCLUSIONS: Changes in QoL over time were not merely a function of
      ageing, or declining health but resulted from factors from a variety of domains
      with loneliness and social participation particularly important. Policies
      concerned with successful ageing and QoL among older adults must consider social
      circumstances as well as physical and psychological well-being.

PMID- 30209725
TI  - Trans-catheter paravalvular leak closure: a single-centre experience.
AB  - INTRODUCTION: A significant paravalvular leak (PVL) is estimated in at least 1-3%
      of patients undergoing surgical aortic and/or mitral valve replacement. Surgical
      repair of a PVL is associated with a 30-day mortality of approximately 10%.
      Percutaneous closure of PVL has emerged as an alternative to surgical repair.
      AIM: We sought to examine the clinical outcomes of patients treated with
      percutaneous closure of PVL at an Irish tertiary referral centre. METHODS: A
      prospective registry was used to record patient and procedural characteristics at
      the time of the PVL procedure. Medical records were retrospectively reviewed to
      assess clinical outcomes during the index hospitalisation and at follow-up.
      RESULTS: A total of 26 PVL procedures were performed in 21 patients (mean age 68
      +/- 13 years, 76% male). Heart failure (HF), haemolysis (HL) or a combination of
      both was the presenting symptoms in 62%, 24% and 14% of patients, respectively.
      In the entire cohort, clinical success was achieved in 18 patients (86%).
      Clinical success was achieved more frequently when HF was the clinical indication
      compared to HL (100% versus 66%). Among patients presenting with isolated HF (n =
      13), the mean NYHA class at baseline and follow-up was 2.5+/- 0.7 and 1.4+/- 0.7,
      respectively. Thirty-day mortality was 0%. There was one (3.8%) major adverse
      procedural complication (stroke). A total of six deaths (28%) occurred during
      follow-up (22 +/- 13.4 months). CONCLUSIONS: Patients with PVL represent a high
      risk patient cohort. Percutaneous PVL offers a safe alternative to surgical PVL
      repair and appears particularly effective in those patients who present primarily
      with HF.

PMID- 30209724
TI  - Review: Porous Metal Filters and Membranes for Oil-Water Separation.
AB  - In recent years, oil-water separation has been widely researched to reduce the
      influences of industrial wastewater and offshore oil spills. A filter membrane
      with special wettability can achieve the separation because of its opposite
      wettability for water phase and oil phase. In the field of filter membrane with
      special wettability, porous metal filter membranes have been much investigated
      because of the associated high efficiency, portability, high plasticity, high
      thermal stability, and low cost. This article provides an overview of the
      research progress of the porous metal filter membrane fabrication and discusses
      the future developments in this field.

PMID- 30209726
TI  - Omitting Completion Dissection in Melanoma? Help is Available for Surgeons Coping
      Without Routine Dissection, But More Work is Needed.

PMID- 30209727
TI  - Contemporary Surgical Management and Outcomes for Anal Melanoma: A National
      Cancer Database Analysis.
AB  - BACKGROUND: Anal melanoma is a rare disease with a poor prognosis. Limited data
      are available regarding oncologic outcomes during the last decade and surgical
      practice patterns. This study aimed to investigate survival and operative
      oncologic outcomes for patients with anal melanoma. METHODS: The National Cancer
      Database (2004-2013) was used to identify patients with nonmetastatic anal
      melanoma who underwent surgical treatment. The primary outcome was overall
      survival. RESULTS: The study enrolled 439 patients in the local excision group
      and 214 patients in the abdominoperineal resection (APR) group. The patients in
      the APR group were older (70 vs 65 years; p < 0.001) and had larger tumors (40 vs
      25 mm; p < 0.001). After resection, the APR patients were more likely to have
      positive lymph nodes (65.7% vs 12.5%; p < 0.001) and less likely to have positive
      margins (10% vs 29.8%; p < 0.001). Overall survival did not differ significantly
      between the APR and local excision patients (hazard ratio [HR], 0.82; 95%
      confidence interval [CI], 0.67-1.01; p = 0.06). The patients undergoing local
      excision showed was a significant survival advantage for those with negative
      margins (HR, 0.70, 95% CI, 0.53-0.93; p = 0.009). Among the patients undergoing
      APR, a significant survival advantage was observed for those with negative nodes
      (HR, 0.50; 95% CI, 0.35-0.69; p = 0.002) and negative margins (HR, 0.34; 95% CI,
      0.15-0.77; p < 0.001). CONCLUSIONS: The overall survival of anal melanoma
      patients is similar after local excision and APR. Patients with positive margins,
      positive lymph nodes, or both have a significantly decreased overall survival.

PMID- 30209728
TI  - Pre-analytical Factors Influence Accuracy of Urine Spot Iodine Assessment in
      Epidemiological Surveys.

PMID- 30209729
TI  - Hair Mineral and Trace Element Content in Children with Down's Syndrome.
AB  - The objective of the present study was to assess the level of minerals and trace
      elements in 40 children with Down's syndrome and 40 controls aged 1-2 years old.
      Hair mineral and trace element analysis was performed using inductively coupled
      plasma mass spectrometry. The obtained data demonstrate that hair levels of Mg,
      P, I, Cr, Si, Zn, and Pb in Down's syndrome patients exceeded the respective
      control values by 36, 36, 93, 57, 45, 28, and 54%, whereas hair mercury was more
      than twofold lower in children with Down's syndrome. The observed difference in
      the levels of trace elements was age-dependent. In particular, in 1-year-olds,
      major differences were observed for essential elements (Cr, Si, Zn), whereas in 2
      year-olds-for toxic elements (Hg, Pb). At the same time, hair P levels in Down's
      syndrome patients were 14 and 35% higher at the age of 1 and 2 years in
      comparison to the respective controls. Multiple regression analysis demonstrated
      that a model incorporating all elements, being characterized by a significant
      group difference, accounted for 42.5% of status variability. At the same time,
      only hair phosphorus was significantly interrelated with Down's syndrome status
      (beta = 0.478; p < 0.001). Principal component analysis (PCA) used As, Ca, Cr,
      Fe, Hg, I, Mg, P, Pb, Se, Si, Sn, and Zn as predictors, with the resulting R2 =
      0.559. The OPLS-DA models also separated between Down's and health control
      groups. Therefore, 1-2-year-old patients with Down's syndrome are characterized
      by significant alterations of mineral and trace element status.

PMID- 30209730
TI  - Importance of mediastinal screening-based observation during endoscopic
      ultrasound to examine gastrointestinal pathologies.
AB  - In all endoscopic ultrasound (EUS) examinations performed at our hospital, the
      heart, vasculature, and mediastinal lymph nodes from the esophagus are observed
      after checking for gastrointestinal pathologies. Since the introduction of EUS
      using a convex linear-array echoendoscope at our hospital in April 2015, EUS
      examinations have been performed in 371 cases for examining pancreaticobiliary
      diseases, submucosal tumors, and other pathologies during the 3-year period, till
      March 2018. We diagnosed 2 patients with asymptomatic cardiovascular disease
      while observing the mediastinum during EUS examination to examine identified
      pancreaticobiliary disease. No subjective symptoms associated with cardiovascular
      disease were observed and the respective conditions had not been identified
      previously in either case. One case involved a left atrial myxoma while the other
      involved a saccular aortic aneurysm in the thoracic aorta. A left atrial tumor
      resection and aortic replacement surgery were performed in each case. Their
      postoperative courses have been favorable. As cardiovascular diseases are often
      life-threatening, as in the present 2 cases, observational screening of the
      cardiovascular system from the esophagus should also be performed during EUS
      examinations just as the pharyngeal region is examined during upper
      gastrointestinal endoscopy.

PMID- 30209732
TI  - Labour productivity loss caused by premature deaths associated with breast
      cancer: results from Spain over a 10-year period.
AB  - BACKGROUND: Breast cancer is one of the most common cancers among women
      worldwide, and is the most common cause of cancer deaths in them. Given that such
      disease has a significant impact on middle-aged women, it can result in
      considerable labour productivity losses. The main objective of this study is
      therefore to analyse labour productivity losses and years of potential working
      life lost as a result of premature deaths from breast cancer in Spain over a 10
      year period (2005-2014). METHOD: To this end, by combining data on average salary
      (Salary Structure Survey), occupation (Active Population Survey) and deaths
      (death registration according to cause of death), a simulation model based on the
      human capital approach was constructed to estimate productivity losses associated
      with premature deaths caused by this disease. RESULTS: The results reveal that
      labour productivity losses in women are estimated to cost 2,137 million euros, as
      a result of the 22,716 deaths occurring during working age and the 292,848 years
      of potential productive life lost. This implies that breast cancer is responsible
      for 10.45% of all estimated female labour productivity losses caused by premature
      deaths in the reference year. CONCLUSION: The article concludes by highlighting
      the major economic impact associated with breast cancer deaths and by pointing
      out future research areas.

PMID- 30209731
TI  - Effects of trastuzumab on locoregional recurrence in human epidermal growth
      factor receptor 2-overexpressing breast cancer patients treated with chemotherapy
      and radiotherapy.
AB  - PURPOSE: In the present study, the ability of adjuvant trastuzumab to reduce
      locoregional recurrence in patients with human epidermal growth factor receptor 2
      (HER2)-overexpressing breast cancer receiving adjuvant chemotherapy and
      radiotherapy (RT) was investigated. MATERIALS AND METHODS: We retrospectively
      included 520 patients with HER2-overexpressing breast cancer who received surgery
      followed by adjuvant RT and cytotoxic chemotherapy from 2003 to 2011. Adjuvant
      trastuzumab was administered to 286 patients. Propensity score matching was
      conducted to compare trastuzumab-treated and non-treated cohorts. RESULTS: Median
      follow-up duration was 7.1 years (range 1.1-14.1 years). Propensity score
      matching yielded 171 matched pairs of patients with no significantly different
      clinical factors. An improved 7-year locoregional control (LRC) rate was observed
      in the trastuzumab-treated cohort compared with the non-treated cohort (95.6% vs.
      89.9%, p = 0.014). Based on multivariate analysis, hormone receptor negativity
      (hazard ratio [HR] = 5.348, p = 0.007), positive lymph node ratio > 0.25 (HR =
      2.549, p = 0.040), and lack of adjuvant trastuzumab (HR = 3.401, p = 0.017) were
      identified as significant risk factors for poor LRC. Adjuvant trastuzumab
      significantly reduced the locoregional recurrence rate in patients with one or
      two risk factors (7-year LRC = 95.0% vs. 84.2%, p = 0.007); however, the benefit
      of adjuvant trastuzumab was non-significant in patients with no risk factors (7
      year LRC = 95.8% vs. 97.9%, p = 0.75). CONCLUSIONS: Adjuvant trastuzumab improved
      LRC in patients with HER2-overexpressing breast cancer receiving adjuvant RT and
      cytotoxic chemotherapy, especially in hormone receptor-negative, HER2-enriched
      subtype, and high positive lymph node ratio breast cancer.

PMID- 30209733
TI  - Living on the Edge: Neighborhood Boundaries and the Spatial Dynamics of Violent
      Crime.
AB  - Neighborhood boundaries are a defining aspect of highly segregated urban areas.
      Yet, few studies examine the particular challenges and spatial processes that
      occur at the bordering region between two neighborhoods. Extending the growing
      literature on spatial interdependence, this article argues that neighborhood
      boundaries-defined as sharp changes in the racial or socioeconomic composition of
      neighborhoods-are a salient feature of the spatial structure with implications
      for violent crime and other outcomes. Boundaries lack the social control and
      cohesion of adjacent homogeneous areas, are contested between groups provoking
      intergroup conflict, and create opportunities for criminal behavior. This article
      presents evidence linking racial neighborhood boundaries to increased violent
      crime. The findings illustrate the importance of neighborhood boundaries for our
      understanding of spatial dimensions of population dynamics above and beyond the
      characteristics of neighborhoods.

PMID- 30209734
TI  - Schmid Type Metaphyseal Chondrodysplasia with a Novel COL10A1 Mutation.
AB  - Schmid type metaphyseal chondrodysplasia (SMCD) is a rare skeletal dysplasia,
      characterized by short stature, short limbs, bowing of the legs, and radiographic
      features of metaphyseal irregularities with fraying and splaying, more severe at
      the knee. It is caused by mutations of the COL10A1 gene. The authors present an
      Indian patient with a novel COL10A1 gene mutation.

PMID- 30209735
TI  - Levetiracetam Induced Neuropsychiatric Manifestation in a 5-year-old Boy.

PMID- 30209736
TI  - The Double Trouble: A Case of Duplicated Extrahepatic Bile Duct with Choledochal
      Cyst.
AB  - Biliary tract shows a large number of anatomic variations and duplication of the
      bile duct is an extremely rare anomaly. It has been reported to be associated
      with other congenital conditions like Abnormal Pancreato Biliary Junction (APBJ),
      biliary atresia and choledochal cyst and may lead to complications like
      cholangitis, choledocholithiasis and malignancy. The clinical presentation may be
      with one of the above complications and the condition usually reveals itself only
      on imaging investigations, as a surprise to the radiologist and the surgeon. Its
      detection is important prior to any biliary tract surgery to prevent inadvertent
      bile duct injury. The authors report a case of a rare subtype of extrahepatic
      bile duct duplication with coexisting choledochal cyst.

PMID- 30209737
TI  - Compulsive Digital Gaming: An Emerging Mental Health Disorder in Children.
AB  - Excessive digital gaming is emerging as a mental health disorder because
      youngsters are losing control of their lives by wasting their time by indulging
      in online multiplayer games. The popularity of the games can be gauged by the
      fact that India's online gaming market of US $360 million is expected to grow to
      $ 1 billion by 2021. Video gaming is an obsessive compulsive disorder. The
      players enjoy creating and building relationships with other online characters,
      which provides a virtual community feeling at the expense of one-to-one social
      interactions and real life bonding. In due course of time, the players are
      preoccupied or "hooked" to the games and display mood swings like irritability,
      restlessness, and aggressive behavior when they are denied the playing gadgets.
      Realizing the multifarious health hazards of digital gaming, WHO has recently
      classified it as a mental health disorder in the 11th revision of its
      International Classification of Diseases (ICD-11) so that it is accorded the
      state health benefits for its prevention and treatment. The technology is both a
      boon as well as a bane, the option is with us. It is important to avoid all
      obsessions or compulsions in life in order to follow the philosophy of "middle
      path".

PMID- 30209738
TI  - Urinary proteomics reveals association between pediatric nephrolithiasis and
      cardiovascular disease.
AB  - PURPOSE: To study (1) the differences in the relative abundance of urinary
      proteins between children with kidney stones (RS) and hypercalciuria,
      hypocitraturia, normal metabolic work-up, and healthy controls (HC); (2) the
      association of these proteins with various diseases. METHODS: Quantitative
      proteomic comparison of pooled urine from RS (N = 30, 24 females, mean age 12.95
      +/- 4.03 years) versus age- and gender-matched HC, using mass spectrometry.
      Relative protein abundance was estimated using spectral counting. Proteins of
      interest were selected using the following criteria: (1) >= 5 spectral counts;
      (2) >= twofold difference in spectral counts; and (3) <= 0.05 p value for the
      Fisher's Exact Test. RESULTS: Of the 1813 proteins identified, 229 met the above
      criteria, with 162 proteins up-regulated in the RS group and 67 up-regulated in
      HC. The largest group of proteins (30 out of 229) was found to be associated with
      cardiovascular disease (CVD). Of those, 16 were involved in coagulation,
      fibrinolysis, and adhesion, 10 in inflammation, 5 in lipid transport and
      metabolism, and 4 in oxidative stress. All except two were exclusively found in
      children with hypercalciuria and hypocitraturia, and were not seen in children
      with normal metabolic work-up. CONCLUSION: Using a proteomic approach, we found a
      significant association between hypercalciuric and hypocitraturic nephrolithiasis
      and CVD in children. The shared risk factors among both diseases are endothelial
      dysfunction and atherosclerosis caused by abnormal coagulation, adhesion,
      disturbance of lipid transport and metabolism, oxidative stress and inflammation.
      Further understanding of the pathophysiological link between nephrolithiasis and
      CVD is necessary for developing new therapeutic targets.

PMID- 30209739
TI  - Identification and functional analyses of new sesame miRNAs (Sesamum indicum L.)
      and their targets.
AB  - Plant microRNAs (miRNAs) have been commonly investigated during many years.
      Hundreds of miRNAs have been identified in many different plant species but there
      is very little information about the function of sesame (Sesamum indicum L.)
      miRNAs. For this purpose, in silico prediction of novel sesame miRNAs based on
      BLAST searches of the expressed sequence tag database was performed, using
      stringent criterias for miRNA annotation. The secondary structures of their
      precursor sequences, potential target genes of conserved and novel miRNAs were
      predicted and subjected to Gene Ontology (GO) annotation. mir447 and mir8140 were
      reported for the first time in sesame. Enrichment analysis of the GO with
      biological processes, cellular component and molecular functions revealed that
      these target genes were potentially involved in different metabolic pathways such
      as transcription factors, metabolism, growth and development, stress-related and
      even plant hormones. Results are valuable for figure out the gene regulation
      mechanism in sesame, using in the medicinal aspect of this plant species.
      Furthermore, these miRNAs and their profiled targets could provide the
      improvement of regulation and management, and even development of desirable
      traits in this plant.

PMID- 30209740
TI  - In vitro antibacterial and anticancer properties of Helicteres hirsuta Lour. leaf
      and stem extracts and their fractions.
AB  - Helicteres hirsuta Lour. (H. hirsuta) has been considered as a herbal medicine
      for the treatment of malaria and diabetes but limited studies have been conducted
      on its anticancer and antibacterial properties. In this study, the in vitro
      antibacterial and anticancer properties of the leaf and stem extracts and their
      two sub-fractions (aqueous and saponin-enriched butanol fractions) prepared from
      H. hirsuta were elucidated. MTT and CCK-8 assays were employed to assess their in
      vitro anticancer properties against various cancer cell lines. The antibacterial
      activity was assessed using the disc diffusion method and minimum inhibitory
      concentration (MIC) values were determined. The results revealed that the saponin
      enriched fractions from H. hirsuta leaves and stems showed the highest
      antibacterial activity against E. coli (MIC values of 2.50 and 5.00 mg/mL,
      respectively) and S. lugdunensis (MIC values of 0.35 and 0.50 mg/mL,
      respectively). Importantly, these saponin-enriched fractions possessed strong
      anticancer activity in vitro towards a range of cancer cell lines including MIA
      PaCa-2 (pancreas); A2780 (ovarian); H460 (lung); A431 (skin); Du145 (prostate);
      HT29 (colon); MCF-7 (breast); SJ-G2, U87, SMA (glioblastoma) and BE2-C
      (neuroblastoma) at low doses (GI50 values of 0.36-11.17 ug/mL). They especially
      revealed potent anti-pancreatic cancer activity in vitro against MIA PaCa-2, BxPC
      3 and CFPAC-1 cells with IC50 values of 1.80-6.43 ug/mL. This finding provides
      scientific evidence of the cytotoxic activity of the extracts prepared from H.
      hirsuta leaves and stems, and suggests further studies to isolate active
      compounds for development of new anticancer agents from these plant extracts.

PMID- 30209741
TI  - Map-based cloning and validation of a gall midge resistance gene, Gm8, encoding a
      proline-rich protein in the rice variety Aganni.
AB  - The Asian rice gall midge (ARGM), Orseolia oryzae is an important insect pest
      causing an annual yield loss of about US$ 80 million in India. Till now 11 R
      genes and seven biotypes of the pest have been characterized and reported. The
      indica rice variety Aganni, a landrace from the state of Kerala, is known to
      carry the gall midge resistance gene Gm8 with HR-type of resistance. This gene
      has been fine mapped within 0.43 Mb region with the flanking markers RM22685 and
      RM22709. We identified 63 possible candidate genes through in silico analysis in
      the reference Nipponbare rice genome between 7.5 and 9.5 Mb region. One of the
      markers targeting the proline rich protein (PRP) gene (LOC_Os08g15080) showed
      polymorphism between the parents and also exhibited complete co-segregation with
      the trait in 426 F10 RIL populations. Functional validation of this gene through
      RT-PCR in contrasting parents and Pre-NILs (near isogenic lines) revealed that
      this is an early responsive gene with rapid induction at 24 h after gall midge
      infestation (hai) followed by subsequent reduction in the expression levels at
      late hours. Validation of this gene in five gall midge resistant rice varieties
      carrying different resistance genes revealed that the induction was unique to
      Aganni rice carrying Gm8 gene. Further, cloning and sequencing of the alleles of
      this gene including promoter region from TN1 (susceptible parent) and Aganni
      (resistant parent) revealed 153 nucleotide substitution, four amino acid
      substitutions and three mutations at putative cis-acting elements in TN1 when
      compared to Aganni. In addition, we also developed a functional marker (PRP-del)
      for detection of the gene for use in marker-assisted introgression of Gm8.

PMID- 30209742
TI  - Lipase immobilization on high water adsorbing capacity bagasse: applications in
      bio-based plasticizer synthesis.
AB  - This study investigates the structure and water adsorbing capacity of bagasse and
      of sodium hydroxide pretreated bagasse. The structures of bagasse and bagasse
      NaOH were compared by SEM and XRD. Candida antarctica lipase B was then
      immobilized on bagasse, bagasse-NaOH and DPA@bagasse-NaOH. The expressed activity
      and immobilization yield of lipase immobilized on bagasse-NaOH (1.0%) was 36% and
      45% higher than that on bagasse. When dopamine (DPA) was used as cationic polymer
      monomer via self-polymerization for mediating immobilization, the protein loading
      amounts and activity of lipase immobilized on DPA@bagasse-NaOH were higher than
      that of bagasse-NaOH. When the DPA concentration was 100 mg/ml, the immobilized
      lipase expressed activity reached its highest value (800 U/g), where the
      immobilization yield achieved 96.8%, which was 3.93-fold of lipase immobilized on
      native bagasse (24.6%). Then the immobilized lipases were used to synthesize a
      bio-based plasticizer. Lipase immobilized on DPA@bagasse-NaOH exhibited a
      significantly improved operational stability. Even after 12 batches, a high ester
      yield (84.2%) was maintained. Additionally, poly (vinyl chloride) PVC blends
      plasticized with methyl oleate as a secondary plasticizer were investigated. It
      was discovered that methyl oleate can be used as an effective bio-based
      plasticizer for PVC. These results indicate that bagasse with high water
      adsorbing capacity and self-polymerized DPA layer could create a favorable
      microenvironment for bio-based plasticizer synthesis in esterification reactions.

PMID- 30209744
TI  - Simulating Eco-evolutionary Processes in an Obligate Pollination Model with a
      Genetic Algorithm.
AB  - Pollination interactions are common, and their maintenance is critical for many
      food crops upon which human populations depend. Pollination is a mutualism
      interaction; together with predation and competition, mutualism makes up the
      triumvirate of fundamental interactions that control population dynamics. Here we
      examine pollination interactions (nectar reward for gamete transport service)
      using a simple heuristic model similar to the Lotka-Volterra models that have
      underpinned our understanding of predation and competition so effectively since
      the 1920s. We use a genetic algorithm to simulate the eco-evolutionary
      interactions of the plant and pollinator populations and examine the
      distributions of the parameter values and zero isoclines to infer the relative
      ubiquity of the various eco-evolutionary outcomes possible in the model. Our
      results suggest that trade-offs between costs and benefits for the pollinator may
      be a key component of obligate pollination systems in achieving adaptive success
      creating and stably occupying mutualist niches.

PMID- 30209743
TI  - Safety Profile of High-Dose Botulinum Toxin Type A in Post-Stroke Spasticity
      Treatment.
AB  - Botulinum toxin type A (BoNT-A) is considered the gold standard for the treatment
      of focal post-stroke spasticity (PSS). However, a recently published study
      estimated that a significant percentage of patients affected by PSS could benefit
      from higher doses of BoNT-A than those permitted by current directives in the
      countries studied. Several studies have reported the use of high doses of BoNT-A
      in the management of patients affected by severe PSS; however, the most important
      adverse effect of this drug might be systemic diffusion of the toxin, which could
      potentially be related to its dose. Even if systemic toxicity is a rare event,
      fear of systemic toxicity is still the most relevant concern regarding use of
      high doses. The aim of our narrative review was to show the state of the art on
      the use of high doses of BoNT-A in patients affected by PSS in order to define
      the safety profile, focusing on both clinical and instrumental assessment of
      systemic effects. Current evidence from the literature suggests that higher doses
      of BoNT-A are effective in reducing spasticity of upper and lower limbs after
      stroke, with rare occurrence of mild adverse effects. The use of high doses seems
      to be an effective and safe therapeutic option to reduce multifocal or
      generalized PSS in selected patients. In particular, the potential role of higher
      doses in order to improve the functional outcome of these patients should be
      noted.

PMID- 30209746
TI  - Acute Invasive Fungal Rhinosinusitis: Frozen Section Histomorphology and
      Diagnosis with PAS Stain.
AB  - Acute invasive fungal rhinosinusitis (AIFRS) is a fulminant infection in
      immunocompromised patients requiring rapid diagnosis (DX), frequently made on
      frozen section (FS) of sinonasal biopsies, followed by prompt surgical
      debridement. However, FS interpretation is often difficult and DX sometimes not
      possible. In this study we sought to characterize reasons for misinterpretation
      and methods to improve diagnostic accuracy. The FS slides from 271 biopsies of
      suspected AIFRS in a 16-year period were reviewed and the morphologic features
      evaluated for their utility in DX. Recurring specific patterns of necrosis were
      identified, which to our knowledge have not been described in the literature.
      Although they provide strong evidence for AIFRS, identifying fungus consistently
      in necrotic tissue is essential for DX. Clues to identifying fungus and pitfalls
      in misidentification were identified, but even with expert knowledge of these, a
      gap in accurate DX remained. The key to FS DX of AIFRS is to improve fungus
      identification in necrotic tissues. Methods had been sought in the past to stain
      fungus at FS without consistent success. The Periodic Acid Schiff's Reaction for
      Fungi was modified by our histopathology department for use on frozen tissue
      (PASF-fs) resulting in effective staining of the fungus. It stained fungus on all
      62 positive slides when applied retrospectively over hematoxylin and eosin (H&E)
      stained FSs and used prospectively at FS for DX. Although knowledge of histologic
      morphology on FS is important, the crucial value of this study is the novel use
      of PASF-fs to identify fungus in the DX of AIFRS.

PMID- 30209747
TI  - Determinants of adoption of alternative response to foot and mouth disease: micro
      level evidence of smallholder pastoralist in north East District, Botswana.
AB  - This paper examines factors influencing the adoption of alternative response to
      Foot and Mouth Disease (FMD) among smallholder beef producers in the dry lands of
      Africa, specifically, North East district in Botswana. Principal component
      analysis was used to categorise FMD responses. Thereafter, a multivariate probit
      regression model was used to examine the effect of socioeconomic and
      institutional factors on the adoption of alternative responses to FMD. The study
      found that household size, opportunity cost incurred, frequency of contact with
      extension officers, training received on FMD, distance to the nearest market, as
      well as distance to grazing and water areas had a positive effect on the adoption
      of alternative responses to the outbreak. We conclude that although producers are
      aware of the detriments of FMD to their livelihoods, some still choose not to
      adopt the responses and socioeconomic and institutional characteristics play a
      role.

PMID- 30209745
TI  - Corynebacterium glutamicum mechanosensitive channels: towards unpuzzling
      "glutamate efflux" for amino acid production.
AB  - Corynebacterium glutamicum has been utilized for industrial amino acid
      production, especially for monosodium glutamate (MSG), the food-additive for the
      "UMAMI" category of taste sensation, which is one of the five human basic tastes.
      Glutamate export from these cells is facilitated by the opening of
      mechanosensitive channels in the cell membrane within the bacterial cell envelope
      following specific treatments, such as biotin limitation, addition of Tween 40 or
      penicillin. A long-unsolved puzzle still remains how and why C. glutamicum
      mechanosensitive channels are activated by these treatments to export glutamate.
      Unlike mechanosensitive channels in other bacteria, these channels are not simply
      osmotic safety valves that prevent these bacteria from bursting upon a hypo
      osmotic shock. They also function as metabolic valves to continuously release
      glutamate as components of a pump-and-leak mechanism regulating the cellular
      turgor pressure. Recent studies have demonstrated that the opening of the
      mechanosensitive channel, MscCG, mainly facilitates the efflux of glutamate and
      not of other amino acids and that the "force-from-lipids" gating mechanism of
      channels also applies to the MscCG channel. The bacterial types of
      mechanosensitive channels are found in cell-walled organisms from bacteria to
      land plants, where their physiological functions have been specialized beyond
      their basic function in bacterial osmoregulation. In the case of the C.
      glutamicum MscCG channels, they have evolved to function as specialized glutamate
      exporters.

PMID- 30209748
TI  - Analysis of domestic animal movements in Colombia (2006-2014) and their possible
      influence on the bovine brucellosis spread.
AB  - Bovine brucellosis is a zoonotic disease that causes great economic losses. The
      disease is endemic in Colombia and animal movements from infected herds carry a
      risk of introduction to other herds. With the objective of analyzing the animal
      movements and determining their relationship with bovine brucellosis, we
      performed a descriptive analysis of the space-time movement of livestock in
      Colombia between 2006 and 2014. Multiple linear regression models (MLR) were
      employed to determine the relationship between brucellosis status and animal
      movements at the province level. The prevalence of bovine brucellosis in cattle
      was the dependent variable, and a total of 14 independent variables related to
      location, year, census, and animal movements were included. The prevalence of
      bovine brucellosis was significantly affected by the province (F = 3.42; P <
      0.001), the year (F = 9.03; P < 0.001), and bovine (F = 5.45; P = 0.02) and
      equine movements (F = 3.8; P = 0.053). Fewer cattle and more horses entered
      provinces with high prevalence than those with low prevalence, indicating the
      possible relationship between the animal movements and the brucellosis infection
      in the country.

PMID- 30209749
TI  - Correction to: Expected Budget Impact and Health Outcomes of Expanded Use of
      Vagus Nerve Stimulation Therapy for Drug-Resistant Epilepsy.
AB  - The article "Expected Budget Impact and Health Outcomes of Expanded Use of Vagus
      Nerve Stimulation Therapy for Drug-Resistant Epilepsy", written by Molly F.
      Purser, Deirdre M. Mladsi, Alan Beckman, Francesca Barion, John Forsey was
      originally published electronically on the publisher's internet portal (currently
      SpringerLink) on August 24, 2018 without open access.

PMID- 30209750
TI  - Comparative Effectiveness of nab-Paclitaxel Plus Gemcitabine vs FOLFIRINOX in
      Metastatic Pancreatic Cancer: A Retrospective Nationwide Chart Review in the
      United States.
AB  - INTRODUCTION: nab-Paclitaxel plus gemcitabine (nab-P + G) and FOLFIRINOX (FFX)
      are among the most common first-line (1L) therapies for metastatic adenocarcinoma
      of the pancreas (MPAC), but real-world data on their comparative effectiveness
      are limited. METHODS: This retrospective cohort study compared the efficacy and
      safety of 1L nab-P + G versus FFX, overall and under specific treatment
      sequences. Medical records were reviewed by 215 US physicians who provided
      information on MPAC patients who initiated 1L therapy with nab-P + G or FFX
      between April 1, 2015 and December 31, 2015. Study outcomes were overall survival
      (OS) and tolerability. OS was compared using Kaplan-Meier curves and adjusted Cox
      proportional hazards models. RESULTS: In total, 654 medical records were
      reviewed, including those of 337 and 317 patients initiated on nab-P + G and FFX
      as 1L MPAC therapy, respectively. nab-P + G-initiated patients were older, less
      likely to have ECOG <= 1, and had more comorbidities than FFX-initiated patients.
      Median OS (mOS) was 12.1 and 13.8 months for nab-P + G- and FFX-initiated
      patients, respectively (HR = 0.99, P = 0.96). Among patients with ECOG <= 1, mOS
      was 14.1 and 13.7 months, respectively (HR = 1.00, P = 0.99). Among patients with
      1L nab-P + G and FFX, 36.1% and 41.3% received 2L therapy and experienced mOS of
      16.3 and 16.6 months, respectively (HR = 1.04, P = 0.76). The rates of diarrhea,
      fatigue, mucositis, and nausea and vomiting were significantly higher in the FFX
      than nab-P + G cohort. CONCLUSION: The real-world survival was similar between
      patients receiving 1L nab-P + G or FFX both overall and among patients who
      received active 2L treatments. In addition, nab-P + G was associated with
      significantly lower rates of common AEs compared with FFX. FUNDING: Celgene.

PMID- 30209751
TI  - Diagnostic Accuracy of Bronchodilator Response for Asthma in a Population of
      South China.
AB  - INTRODUCTION: A significant bronchodilator response is commonly defined as a 12%
      or greater and 200 ml or greater change in FEV1 from baseline according to the
      2005 American Thoracic Society (ATS)/European Respiratory Society (ERS)
      criterion. A number of studies have shown that the ATS/ERS criterion has
      limitations in asthma diagnosis, and some experts have argued for correcting the
      criteria. The aim of this study is to investigate the diagnostic value of acute
      bronchodilator response for asthma in a Southern Chinese population. METHODS: We
      prospectively evaluated 805 patients with obstructive lung disease (309 for
      asthma, 496 for non-asthma). Spirometry was performed according to the ATS/ERS
      guidelines. Data were analyzed by SPSS 18.0. The receiver-operating
      characteristic (ROC) curve was drawn to assess the diagnostic accuracy of the
      ATS/ERS criterion based on FEV1. Linear regression was used to analyze the
      factors of FEV1 change. RESULTS: The sensitivity and specificity of the acute
      bronchodilator test when judged by the ATS/ERS criteria (200 ml or higher and 12%
      improvement) were 68.6% and 78.2%, respectively. For the ATS/ERS criteria, the
      Youden Index, which comprehensively reflects the authenticity of a diagnostic
      test, was 46.8%. The absolute change of FEV1 positively correlated with baseline
      FEV1 and weight and negatively with age, while the percentage change of FEV1 was
      negatively correlated with baseline FEV1, age and height and positively with
      weight. Compared with the different diagnostic values, when ?FEV1 was 195 ml and
      ?FEV1i% was 14%, the Youden Index was the largest (48.2%) and the diagnostic
      capability of the test the biggest. CONCLUSIONS: The ATS/ERS criterion for acute
      bronchodilator response might not be completely suitable for asthma in the
      Chinese population. TRIAL REGISTRATION: Chinese Clinical Trial Registry (Registry
      ID: ChiCTR-DDT-14004976). FUNDING: This work was supported by the National
      Natural Science Foundation of China (grant nos. 81670027, 81270080).

PMID- 30209752
TI  - Information exchange between patients with Lynch syndrome and their genetic and
      non-genetic health professionals: whose responsibility?
AB  - Individuals at high risk for Lynch syndrome (LS) should be offered genetic
      counselling, since preventive options are available. However, uptake of genetic
      services and follow-up care are currently suboptimal, possibly caused by
      inadequate exchange of information. Therefore, this qualitative study aims to
      gain insight in the process of information exchange between patients diagnosed
      with LS and their non-genetic (i.e., general practitioner, gastroenterologist,
      gynaecologist) and genetic (i.e., clinical geneticist or genetic counsellor)
      health professionals concerning referral for genetic counselling and follow-up
      care. Participants comprised 13 patients diagnosed with LS (8 index patients and
      5 of their affected relatives) and 24 health professionals (6 general
      practitioners, 8 gastroenterologists, 6 gynaecologists and 4 genetic health
      professionals). Analysis of the interview transcripts was performed in parallel
      and again after the interviews, following guidelines for qualitative research and
      using MAXQDA software. The main finding is that patients may 'get lost' between
      health professionals who lack a clear overview of their own and each other's role
      and responsibilities in the referral and follow-up care for patients with
      possible LS. Education of non-genetic health professionals and optimisation of
      communication between health professionals might help to enable more timely
      diagnosis of LS and allow patients to address their doubts and questions to the
      most appropriate healthcare professional.

PMID- 30209753
TI  - Historical overview of development in methods to estimate burden of disease due
      to congenital disorders.
AB  - Congenital disorders (often also called birth defects) are an important cause of
      mortality and disability. They encompass a wide range of disorders with differing
      severity that can affect any aspect of structure or function. Understanding their
      epidemiology is important in developing appropriate services both for their
      prevention and treatment. The need for epidemiological data on congenital
      disorders has been recognised for many decades. Here, we provide a historical
      overview of work that has led to the development of the Modell Global Database of
      Congenital Disorders (MGDb)-a tool that can be used to generate evidence-based
      country, regional and global estimates of the birth prevalence and outcomes of
      congenital disorders.

PMID- 30209755
TI  - Optimizing the diagnostic workup of infective endocarditis: An urgent need for
      studies focused on defining the decision-making process.

PMID- 30209754
TI  - Diagnostic performance of an artificial intelligence-driven cardiac-structured
      reporting system for myocardial perfusion SPECT imaging.
AB  - OBJECTIVES: To describe and validate an artificial intelligence (AI)-driven
      structured reporting system by direct comparison of automatically generated
      reports to results from actual clinical reports generated by nuclear cardiology
      experts. BACKGROUND: Quantitative parameters extracted from myocardial perfusion
      imaging (MPI) studies are used by our AI reporting system to generate
      automatically a guideline-compliant structured report (sR). METHOD: A new
      nonparametric approach generates distribution functions of rest and stress,
      perfusion, and thickening, for each of 17 left ventricle segments that are then
      transformed to certainty factors (CFs) that a segment is hypoperfused, ischemic.
      These CFs are then input to our set of heuristic rules used to reach diagnostic
      findings and impressions propagated into a sR referred as an AI-driven structured
      report (AIsR). The diagnostic accuracy of the AIsR for detecting coronary artery
      disease (CAD) and ischemia was tested in 1,000 patients who had undergone
      rest/stress SPECT MPI. RESULTS: At the high-specificity (SP) level, in a subset
      of 100 patients, there were no statistical differences in the agreements between
      the AIsr, and nine experts' impressions of CAD (P = .33) or ischemia (P = .37).
      This high-SP level also yielded the highest accuracy across global and regional
      results in the 1,000 patients. These accuracies were statistically significantly
      better than the other two levels [sensitivity (SN)/SP tradeoff, high SN] across
      all comparisons. CONCLUSIONS: This AI reporting system automatically generates a
      structured natural language report with a diagnostic performance comparable to
      those of experts.

PMID- 30209756
TI  - Viability assessment by 18F-FDG PET in a patient with a large left ventricular
      aneurysm and obstructive coronary artery disease.

PMID- 30209757
TI  - Prognostic value of left ventricular mechanical dyssynchrony indices in long
      standing type II diabetes mellitus with normal perfusion and left ventricular
      systolic functions on SPECT-MPI.
AB  - OBJECTIVE: To test whether phase analysis indices from SPECT-MPI for left
      ventricular mechanical dyssynchrony (LVMD) are predictors of major adverse
      cardiac events (MACEs) in long-standing diabetes mellitus (DM). METHODS: A total
      of 136 DM patients with normal perfusion and left ventricular systolic functions
      were followed up for about two years and divided into two groups according to the
      presence and the absence of MACEs. RESULT: Thirteen (9.5%) patients experienced
      MACEs during follow-up. Patients experiencing MACEs showed significantly higher
      phase standard deviation (PSD) and wider phase bandwidth (PBW) than those who did
      not. Moreover, both PSD and PBW showed significant correlations (r = 0.25 and
      0.27; P < 0.05) with duration of DM. Logistic regression analysis revealed
      significant associations of DM duration, microvascular complications, and LVMD
      indices for predicting MACEs. Kaplan-Meier event-free survival analysis revealed
      significantly higher rate of MACEs (Logrank = 10.02; P = 0.001) in patients with
      high PSD and wide PBW. An overall fit model consisting of high-PSD and wide-PBW
      group was improved with the addition of microvascular complications (chi2 = 15.9;
      P = 0.03) and further by addition of DM duration of >= 15 years (chi2 = 24.3; P =
      0.007) as variables. CONCLUSION: LVMD indices are novel prognostic markers in
      diabetic patients with normal perfusion and left ventricular systolic functions
      and their increases in magnitudes with DM-duration and in the presence of
      microvascular complications.

PMID- 30209758
TI  - Proliferation and In Vitro Wound Healing Effects of the Microniosomes Containing
      Narcissus tazetta L. Bulb Extract on Primary Human Fibroblasts (HDFs).
AB  - PURPOSE: In Traditional Persian Medicine (TPM), different natural treatments have
      been suggested for skin damages such as Narcissus tazetta L. bulb application.
      New drug delivery systems such as niosomes have shown considerable increase
      transdermal drug delivery through stratum corneum, the main barrier against
      substances transport into skin. The aim of this study is preparation of niosomal
      formulations from N. tazetta bulb extract and evaluation of its in vitro wound
      healing effect. MATERIALS AND METHODS: Non-ionic surfactant vesicles (NSVs or
      niosomes) were prepared by film hydration method from percolated extract of N.
      tazetta bulb. A number of 12 niosomal formulations (F1-F12) were prepared using
      different proportions of Span 60/Tween 60/cholesterol and 80% methanol
      dissolved/aqueous PEN (percolation extract of N. tazetta) (30 and 50 mg/ml).
      Their morphology, particle size, physical and chemical stability and
      encapsulation efficiency was studied. In vitro wound healing effect of various
      concentrations of the best PEN niosomal formulation (F9) was evaluated in
      comparison to PEN on human dermal fibroblasts (HDFs). RESULTS: Increasing the
      aqueous/methanolic PEN concentration from 3 to 5% resulted size reduction of NSVs
      with statistically significant difference (p < 0.05). F9 showed the most
      physicochemical stability and was chosen for in vitro wound healing effect. This
      formulation exhibited significantly effects (p < 0.05) on cell proliferation in
      HDF cells at 1.562 and 3.125 MUg/ml compared with the untreated cells using
      neutral red assay. CONCLUSION: Formulation of PEN in niosome carrier
      significantly decreased the gap width on human dermal fibroblasts. Graphical
      abstract Schematic processes of proliferation effect of narcisus tazetta bulb on
      fibroblast cells.

PMID- 30209759
TI  - Magnetic delivery of antitumor carboplatin by using PEGylated-Niosomes.
AB  - To improve the efficiency of niosomal drug delivery, here we employed two
      tactics. First, niosomes were magnetized using Fe3O4@SiO2 mangnetic
      nanoparticles, and second, their surface was modified by PEGylation. PEGylation
      was intended for increasing the bioavailability of niosomes, and magnetization
      was used for rendering them capable of targeting specific tissues. These
      PEGylated magnetic niosomes were also loaded with Carboplatin, an antitumor drug.
      Next, these niosomes were studied in terms of size, morphology, zeta potential,
      and drug entrapment efficiency. Then, the in vitro drug release from these
      modified niosomes was compared to that of both naked and nonmagnetized niosomes.
      Interestingly, although loading of naked-niosomes with magnetic particles lead to
      an increase in the rate of drug release, PEGylation of these magnetized niosomes
      caused a more sustained drug release. Thus, PEGylation of magnetic niosomes,
      besides improving their bioavailability, caused a slower and sustained release of
      the drug over time. Finally, studying the in vitro effectives of niosomal
      formulations towards MCF-7, a breast cancer cell line, showed that PEGylated
      magnetic niosomes had a satisfactory toxicity towards these cells in the presence
      of an external magnetic field. In conclusion, PEGylated magnetic niosomes showed
      enhanced qualities regarding the controlled release and delivery of drug.
      Graphical abstract ?.

PMID- 30209761
TI  - Early P2X7R-dependent activation of microglia during the asymptomatic phase of
      autoimmune encephalomyelitis.
AB  - Microglia-mediated neuroinflammation accompanies many central nervous system
      (CNS) diseases, including multiple sclerosis (MS), and is strongly dependent on
      the purinergic P2X7 receptor. The nature of the inflammatory response in MS is
      studied for decades indicating, that proinflammatory microgliosis is involved in
      advanced stages of MS and is associated with active tissue damage and
      neurological dysfunctions. Evidence on the role of microgliosis in initial stages
      of the disease is scarce. Thus, in the present study, we investigated the time
      course of microglial activation in rat brain subjected to experimental autoimmune
      encephalomyelitis (EAE) which is the animal model of MS. We show that activation
      of microglia occurs in brains of immunized rats at a very early stage of EAE,
      well before the development of neurological symptoms of the disease. Enhanced
      immunoreactivity of microglia/macrophage-specific protein Iba-1, together with
      morphological features of microgliosis, was identified beginning at day 4 post
      immunization. Concomitantly, microglial expression of P2X7R was also examined.
      Moreover, our results reveal that administration of Brilliant Blue G, an
      antagonist of P2X7R, delays the onset of the disease and partially inhibits
      development of neurological symptoms in EAE rats. Blockage of P2X7R significantly
      reduces activation of microglia as confirmed by decreased Iba-1 immunoreactivity
      and suppresses neuroinflammation in EAE rat brains, as indicated by decreased
      protein levels of investigated proinflammatory cytokines: IL-1beta, IL-6 and TNF
      alpha. Our results indicate that microglia are involved in inducing
      neuroinflammation at a very early stage of MS/EAE via a P2X7R-dependent
      mechanism.

PMID- 30209763
TI  - Nuclear magnetic resonance-based metabolomic investigation reveals metabolic
      perturbations in PM2.5-treated A549 cells.
AB  - Exposure to PM2.5 is associated with an increased risk of lung diseases, and
      oxidative damage is the main reason for PM2.5-mediated lung injuries. However,
      little is known about the early molecular events in PM2.5-induced lung toxicity.
      In the present study, the metabolites in PM2.5-treated A549 cells were examined
      via a robust and nondestructive nuclear magnetic resonance (NMR)-based metabolic
      approach to clarify the molecular mechanism of PM2.5-induced toxicity. NMR
      analysis revealed that 12 metabolites were significantly altered in PM2.5-treated
      A549 cells, including up-regulation of alanine, valine, lactate, omega-6 fatty
      acids, and citrate and decreased levels of gamma-aminobutyric acid, acetate,
      leucine, isoleucine, D-glucose, lysine, and dimethylglycine. Pathway analysis
      demonstrated that seven metabolic pathways which included alanine, aspartate and
      glutamate metabolism, aminoacyl-tRNA biosynthesis, taurine and hypotaurine
      metabolism, arginine and proline metabolism, starch and sucrose metabolism,
      valine, leucine and isoleucine biosynthesis, and tricarboxylic acid cycle were
      mostly influenced. Our results indicate that NMR technique turns out to be a
      simple and reliable method for exploring the toxicity mechanism of air pollutant.

PMID- 30209762
TI  - Serum P-glycoprotein level: a potential biomarker of DMARD failure in patients
      with rheumatoid arthritis.
AB  - OBJECTIVES: To evaluate the utility of elevated serum P-glycoprotein (P-gp) as a
      risk marker of therapeutic response failure in rheumatoid arthritis (RA) patients
      treated with disease-modifying antirheumatic drugs (DMARDs). METHODS: A cross
      sectional study was conducted in 151 RA patients. Patients were classified into
      two groups according to the response achieved in terms of the disease activity
      score (DAS)28 after >= 6 months: (1) patients with a therapeutic response to
      DMARDs, with DAS28 < 3.2; and (2) patients without a response to DMARDs, with
      persistent DAS28 >= 3.2. We explored a wide group of clinical factors associated
      with therapeutic resistance. Serum P-gp levels were measured by ELISA. The risk
      of P-gp elevation as a marker of failure to achieve a therapeutic response to
      DMARDs was computed using multivariate logistic regression. RESULTS: Serum P-gp
      levels were significantly higher in RA patients (n = 151) than in the controls (n
      = 30) (158.70 +/- 182.71 ng/mL vs. 14.12 +/- 8.97 ng/mL, p < 0.001). The P-gp
      level was correlated with the DAS28 score (r = 0.39, p < 0.001). RA patients with
      DMARD failure had higher serum P-gp levels than patients with a therapeutic
      response (206 +/- 21.47 ng/mL vs 120.60 +/- 15.70 ng/mL; p = 0.001). High P-gp
      levels increased the risk of DMARD failure (OR 3.36, 95% CI 1.54-7.27, p =
      0.001). After adjusting for confounding variables, elevated P-gp remained
      associated with DMARD failure (OR 2.64, 95% CI 1.29-5.40, p = 0.01). CONCLUSION:
      Elevated serum P-gp is associated with DMARD failure. The P-gp level can be
      considered a clinical tool for evaluating the risk of DMARD failure in patients;
      however, future prospective studies should be performed to evaluate the utility
      of this marker in predicting long-term responses.

PMID- 30209764
TI  - Total and available metal concentrations in soils from six long-term
      fertilization sites across China.
AB  - Approximately 19% of agricultural soils in China are contaminated by heavy
      metals. However, the effects of agricultural management practices on soil
      contamination are not well understood. Taking advantage of six long-term (23-34
      years) field sites across China, this study examined the effects of different
      agricultural fertilization treatments, including control (no fertilization),
      inorganic nitrogen, phosphorus and potassium fertilization (NPK), manure
      fertilization (M), and NPK plus manure fertilization (NPKM), on the total and
      available metal concentrations in soils. The results showed that after 23-34
      years of fertilization, the M and NPKM treatments significantly increased the
      total concentration of cadmium (Cd), copper (Cu), and zinc (Zn) in soils compared
      with the concentrations measured for the control and NPK treatments. In contrast,
      the fertilization treatments had almost no influence on soil lead (Pb) and nickel
      (Ni) concentrations. The results of analysis via diffusive gradients in thin
      films demonstrated that long-term sheep or cattle manure fertilization increased
      the available metals, especially Cd, Cu, and Zn, but long-term swine manure
      application decreased the available metals, except for Cu and Zn, in soils.
      Further analysis revealed that the manure source, soil pH level, and
      biogeochemical properties of metals affected the availability of Cd, Cu, Pb, Zn,
      and Ni in soils. Collectively, organic fertilizers had the potential to reduce
      metal uptake by crops, but caution should be taken to reduce metal concentrations
      in manure.

PMID- 30209760
TI  - Effect of Cinnamic acid and FOLFOX in diminishing side population and
      downregulating cancer stem cell markers in colon cancer cell line HT-29.
AB  - PURPOSE: There is a lot of evidence suggesting that a small subset of cancer
      cells resistant to conventional chemotherapy and radiotherapy and known as cancer
      stem cells (CSCs) is responsible for promoting metastasis and cancer relapse.
      Therefore, targeting and eliminating the CSCs could lead to higher survival rates
      and a better quality of life. In comparison with conventional chemical drugs that
      may not be effective against CSCs, phytochemicals are strong anti-CSCs agents.
      The current study examines the effect of 5-fluorouracil plus oxaliplatin (FOLFOX)
      as a common chemotherapy drug on colorectal cancer as well as the influence of
      Cinnamic acid (CINN) as a plant-derived phytochemical on colon cancer stem-like
      cells in HT-29 adenocarcinoma cell line. METHODS: The anti-proliferative effect
      of FOLFOX and CINN was determined using MTT [3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide] assay. Flow cytometry analysis was used for the
      identification of side population (SP), CD44, and CD133 positive cells. The
      expression of OCT4, NANOG, ABCB1, and ALDH1A was assessed by RT-PCR. RESULTS: The
      FOLFOX and CINN decreased cell viability in certain drug concentrations: IC50 =
      5,40 MUM oxaliplatin +220 MUM 5-fluorouracil, and 13,50 mM for CINN. The CSC
      associated markers (OCT4, NANOG, ABCB1, and ALDH1A) and the proportion of cancer
      stem-like cells (SP cells, CD44, and CD133 positive cells) were downregulated
      following the treatment of HT-29 adenocarcinoma cell line with IC50
      concentrations of FOLFOX and CINN. CONCLUSION: Our data suggests that CINN, a
      naturally occurring component, could be more effective than FOLFOX treatment in
      reducing the cancer stem-like cells and expression of CSC markers from HT-29
      colon cancer cells. Graphical abstract ?.

PMID- 30209765
TI  - Stress response of NAD+-dependent formate dehydrogenase in Gossypium hirsutum L.
      grown under copper toxicity.
AB  - Cotton (Gossypium hirsutum L.), which is not directly involved in the food chain,
      appears to be a suitable candidate to remove heavy metals from the food chain and
      to be a commercial plant which could be planted in contaminated soils. The key
      point of this approach is selection of the right genotype, which has heavy metal
      resistance or hyperaccumulation properties. Therefore, in the present study, two
      G. hirsutum genotypes, Ersan-92 and N-84S, were grown under copper stress and
      investigated to obtain further insights about the heavy metal tolerance
      mechanisms of plants by focusing on the expression of NAD+-dependent formate
      dehydrogenase (FDH). In accordance with the results, which were obtained from RT
      PCR analysis and activity measurements, in the Ersan-92 root tissue, FDH activity
      increased significantly with increasing metal concentrations and a 6.35-fold
      higher FDH activity was observed in the presence of 100-MUM Cu. As opposed to
      Ersan-92, the maximum FDH activity in the roots of N-84S, which were untreated
      with copper as the control plants, was measured as 0.0141-U mg-1 g-1 FW, and the
      activity decreased significantly with the increasing metal concentrations. The
      metallothionein (GhMT3a) transcript level of the plants grown in a medium
      containing different Cu concentrations showed nearly the same pattern as that of
      the FDH gene transcription. It was observed that while the tolerance of N-84S in
      the lower Cu concentration reduces remarkably, Ersan-92 continues to struggle up
      to 100-MUM Cu. The results of the SOD analysis also confirm this activity of
      Ersan-92 against the Cu stress.

PMID- 30209767
TI  - Facile synthesis of Fe3O4@MOF-100(Fe) magnetic microspheres for the adsorption of
      diclofenac sodium in aqueous solution.
AB  - In this research, the adsorptive removal of diclofenac sodium, one of the
      representative pharmaceuticals and personal care products, from aqueous solution
      using Fe3O4@MOF-100(Fe) magnetic microspheres was studied for the first time. The
      Fe3O4@MOF-100(Fe) microspheres exhibit strong magnetism and stability, which were
      observed as a core-shell structure. The maximum adsorption capacity of Fe3O4@MOF
      100(Fe) for diclofenac sodium can reach 377.36 mg L-1, which was higher than most
      of the adsorbents reported. The adsorption kinetics follows the pseudo-second
      order kinetic equation. And the adsorption equilibrium of DCF can be described
      with Langmuir isotherm. In the cycle experiment, Fe3O4@MOF-100(Fe) material
      performed high adsorption efficiency for low-concentration diclofenac sodium
      solution, and the removal rate can still reach 80% after 5 cycles of adsorption
      without desorption. The mechanisms including electrostatic interaction, H-bond
      interaction, and pi-pi interaction that coexisted in the adsorption processes
      would be of benefit to enhance the adsorption capacity. The Fe3O4@MOF-100(Fe)
      magnetic microspheres offer exciting opportunities for further application.

PMID- 30209768
TI  - Baccharis dracunculifolia (Asteraceae) essential oil toxicity to Culex
      quinquefasciatus (Culicidae).
AB  - The control of mosquitoes by means of chemical insecticides has been a problem,
      mainly due to the possibility of resistance developed by insects to xenobiotics.
      For this reason, demand for botanical insecticides has increased. In this sense,
      the present work aims to verify the susceptibility and morphological and
      biochemical alterations of Culex quinquefasciatus larvae after exposure to
      essential oil (EO) of leaves of Baccharis dracunculifolia. To observe the
      larvicidal action, larvae were exposed to EO at concentrations of 25, 50, 100,
      and 200 mg/L, until their emergence to adults. The control group was exposed to
      deionized water and dimethyl sulfoxide. Morphological analyses were also carried
      out using hematoxylin and eosin, mercury bromophenol blue, Nile blue, and
      periodic acid Schiff. Biochemical analyses of total glucose, triacylglyceride
      (TAG), protein, and acetylcholinesterase levels were performed. The phytochemical
      analysis of the EO showed (E)-nerolidol as the major compound (30.62%). Larvae
      susceptibility results showed a LC50 of 34.45 mg/L for EO. Morphological analysis
      showed that there were histological changes in midgut. For biochemical analyses,
      the glucose level in the larvae exposed to EO for 24 h decreased significantly,
      unlike the TAG levels, which increased. The total protein level of the larvae
      also increased after exposure for 24 h, and acetylcholinesterase levels decreased
      significantly. Taking all our data into account, we can conclude that EO causes
      destabilization in larva, leading to histological changes, metabolic deregulation
      and, consequently, their death.

PMID- 30209770
TI  - Formation characteristics of carbonaceous and nitrogenous disinfection by
      products depending on residual organic compounds by CGS and DAF.
AB  - Allogenic organic matter (AOM) composed of extracellular and intracellular
      organic matter (EOM and IOM) is a major precursor of halogenated carbonaceous and
      nitrogenous disinfection by-products (C-DBPs and N-DBPs) upon chlorination. The
      EOM and IOM extracted from Microcystis aeruginosa were analyzed based on bulk
      parameters and organic fractions with different molecular weight by liquid
      chromatography with organic carbon detection (LC-OCD). It investigated the
      efficiency of a conventional gravity system (CGS) and dissolved air flotation
      (DAF) in the removal of organic precursors, together with measurement of the
      formation of four major trihalomethanes (THMs) and haloacetonitriles (HANs) in
      treated water upon chlorination. The results showed that EOM accounted for 59% of
      building blocks and humic substances, whereas for IOM, 54% were low molecular
      weight (LMW) neutrals. Both CGS and DAF showed 57-59% removal of dissolved
      organic carbon (DOC) from EOM and IOM. Regarding DON removal, DAF was found to be
      more effective, i.e., 8% higher than CGS for EOM. Moreover, the removal of LMW
      acids and neutrals (not easy to remove and are major precursors of DBPs) from EOM
      and IOM by DAF was higher than from CGS. The amounts of DBPs measured in all the
      samples treated for interchlorination were much lower than in the samples for
      prechlorination. Although the precursors of EOM had a higher concentration than
      in IOM, THMs and HANs were detected for IOM at a higher concentration, which
      might be attributed to higher amounts of aromatic, aliphatic moisture and protein
      compounds in the IOM. Comparatively, DAF showed lower THM and HAN values than CGS
      water, particularly for IOM. Also, DAF showed a sharp decrease in THMs and an
      insignificant increase in HANs according to time.

PMID- 30209766
TI  - Lifestyle chemical carcinogens associated with mutations in cell cycle regulatory
      genes increases the susceptibility to gastric cancer risk.
AB  - In the present study, we correlated the various lifestyle habits and their
      associated mutations in cell cycle (P21 and MDM2) and DNA damage repair (MLH1)
      genes to investigate their role in gastric cancer (GC). Multifactor
      dimensionality reduction (MDR) analysis revealed the two-factor model of oral
      snuff and smoked meat as the significant model for GC risk. The interaction
      analysis between identified mutations and the significant demographic factors
      predicted that oral snuff is significantly associated with P21 3'UTR mutations. A
      total of five mutations in P21 gene, including three novel mutations in intron 2
      (36651738G > A, 36651804A > T, 36651825G > T), were identified. In MLH1 gene, two
      variants were identified viz. one in exon 8 (37053568A > G; 219I > V) and a novel
      37088831C > G in intron 16. Flow cytometric analysis predicted DNA aneuploidy in
      07 (17.5%) and diploidy in 33 (82.5%) tumor samples. The G2/M phase was
      significantly arrested in aneuploid gastric tumor samples whereas high S-phase
      fraction was observed in all the gastric tumor samples. This study demonstrated
      that environmental chemical carcinogens along with alteration in cell cycle
      regulatory (P21) and mismatch repair (MLH1) genes may be stimulating the
      susceptibility of GC by altering the DNA content level abnormally in tumors in
      the Mizo ethic population.

PMID- 30209769
TI  - Human health risks of Hg, As, Mn, and Cr through consumption of fish, Ticto barb
      (Puntius ticto) from a tropical river, Bangladesh.
AB  - Metals tend to accumulate in higher organisms, e.g., fish and human through
      biomagnification effects in food chain. So, their presence in any component of
      the environment has become a global ecosystem and health concern. Here, we
      measured four health concerned metals like As, Cr, Mn, and Hg via inductively
      coupled plasma-mass spectrometry (ICP-MS) and analyzed applying some chemometrics
      for the assessment of human health risk through consumption of Puntius ticto, a
      very commonly consumed small fish in Bangladesh. The average concentration (wet
      weight) of metals was in the following descending order: Hg (0.006 mg/kg) > Cr
      (0.004 mg/kg) > Mn (0.003 mg/kg) > As (0.002 mg/kg). Hg level exceeded the
      provisional tolerable weekly intake (PTWI), and all other metals were within the
      permissible limit. The estimated daily intake (EDI) index of heavy metals showed
      that all the concentration levels were under the recommended daily intake (RDA)
      except Hg. Increased level of Hg is of particular concern to human health due to
      its biomagnification nature and can cause several neurological and physiological
      disorders including kidney failure. The total target hazard quotients (TTHQs) and
      carcinogenic risk (CR) matrices revealed that the intakes of Hg and As through
      fish consumption were higher than the recommended values, indicating consumers'
      remain non-carcinogenic and carcinogenic (THQ > 1; CR > 10-5) health risks for
      lifetime consumption. Multivariate analyses (cluster and principal component)
      explained the sources of heavy metals in the study area originating from both
      anthropogenic and geological origin.

PMID- 30209771
TI  - A critical evaluation of health risk assessment of modified mycotoxins with a
      special focus on zearalenone.
AB  - A comprehensive definition introducing the term "modified mycotoxins" to
      encompass all possible forms in which mycotoxins and their modifications can
      occur was recently proposed and has rapidly gained wide acceptance within the
      scientific community. It is becoming increasingly evident that exposure to such
      modified mycotoxins due to their presence in food and feed has the potential to
      pose a substantial additional risk to human and animal health. Zearalenone (ZEN)
      is a well-characterized Fusarium toxin. Considering the diversity of modified
      forms of ZEN occurring in food and feed, the toxicologically relevant endocrine
      activity of many of these metabolites, and the fact that modified forms add to a
      dietary exposure which approaches the tolerable daily intake by free ZEN alone,
      modified forms of ZEN present an ideal case study for critical evaluation of
      modified mycotoxins in food safety. Following a summary of recent scientific
      opinions of EFSA dealing with health risk assessment of ZEN alone or in
      combination with its modified forms, uncertainties and data gaps are highlighted.
      Issues essential for evaluation and prioritization of modified mycotoxins in
      health risk assessment are identified and discussed, including opportunities to
      improve exposure assessment using biomonitoring data. Further issues such as
      future consideration of combinatory effects of the parent toxin with its modified
      forms and also other compounds co-occurring in food and feed are addressed. With
      a particular focus on ZEN, the most pressing challenges associated with health
      risk assessment of modified mycotoxins are identified and recommendations for
      further research to fill data gaps and reduce uncertainties are made.

PMID- 30209772
TI  - Nrf2-Mediated System xc- Activation in Astroglial Cells Is Involved in HIV-1 Tat
      Induced Neurotoxicity.
AB  - HIV-associated neurocognitive disorders (HANDs) affect a large part of HIV
      infected patients, despite highly active antiretroviral therapy. HANDs occur in
      the absence of a direct infection of neurons. Nevertheless, viral proteins (e.g.,
      Tat) are capable to cause neuronal dysfunction via oxidative stress, but the
      cellular pathways leading to HANDs are not yet fully defined. Here, we
      investigated the effects of Tat on Nrf2-mediated antioxidant response and system
      xc- expression in U373 human astroglial cells. Moreover, the effect of Tat
      producing astrocytes on neuronal cell viability was assessed using SH-SY5Y cells
      as a culture model. We demonstrated that Tat produced by astrocytes was able to
      induce Nrf2 activation and system xc- expression in astrocytes, thus reducing
      cell viability of co-cultured neuronal cells. Furthermore, sulfasalazine, a
      specific system xc- inhibitor, was able to reduce extracellular glutamate and to
      prevent the reduction of neuronal viability, thus demonstrating that the
      neurotoxic effect was dependent on an increased glutamate release through the
      transporter. Our findings provide evidence of the involvement of astroglial
      Nrf2/system xc- pathway in the neurotoxicity induced by HIV-1 Tat protein,
      thereby suggesting how astrocytes may exacerbate neurodegeneration through the
      conversion of an antioxidant response to excitotoxicity.

PMID- 30209773
TI  - Correction to: Zika Virus and the Metabolism of Neuronal Cells.
AB  - The original version of this article unfortunately contained mistake.

PMID- 30209774
TI  - Cerebrospinal Fluid Ceruloplasmin, Haptoglobin, and Vascular Endothelial Growth
      Factor Are Associated with Neurocognitive Impairment in Adults with HIV
      Infection.
AB  - Dysregulated iron transport and a compromised blood-brain barrier are implicated
      in HIV-associated neurocognitive disorders (HAND). We quantified the levels of
      proteins involved in iron transport and/or angiogenesis-ceruloplasmin,
      haptoglobin, and vascular endothelial growth factor (VEGF)-as well as biomarkers
      of neuroinflammation, in cerebrospinal fluid (CSF) from 405 individuals with HIV
      infection and comprehensive neuropsychiatric assessments. Associations with HAND
      [defined by a Global Deficit Score (GDS) >= 0.5, GDS as a continuous measure
      (cGDS), or by Frascati criteria] were evaluated for the highest versus lowest
      tertile of each biomarker, adjusting for potential confounders. Higher CSF VEGF
      was associated with GDS-defined impairment [odds ratio (OR) 2.17, p = 0.006] and
      cGDS in unadjusted analyses and remained associated with GDS impairment after
      adjustment (p = 0.018). GDS impairment was also associated with higher CSF
      ceruloplasmin (p = 0.047) and with higher ceruloplasmin and haptoglobin in
      persons with minimal comorbidities (ORs 2.37 and 2.13, respectively; both p =
      0.043). In persons with minimal comorbidities, higher ceruloplasmin and
      haptoglobin were associated with HAND by Frascati criteria (both p < 0.05), and
      higher ceruloplasmin predicted worse impairment (higher cGDS values, p < 0.01).
      In the subgroup with undetectable viral load and minimal comorbidity, CSF
      ceruloplasmin and haptoglobin were strongly associated with GDS impairment (ORs
      5.57 and 2.96, respectively; both p < 0.01) and HAND (both p < 0.01).
      Concurrently measured CSF IL-6 and TNF-alpha were only weakly correlated to these
      three biomarkers. Higher CSF ceruloplasmin, haptoglobin, and VEGF are associated
      with a significantly greater likelihood of HAND, suggesting that interventions
      aimed at disordered iron transport and angiogenesis may be beneficial in this
      disorder.

PMID- 30209776
TI  - A running suture line for aortic valve replacement does not increase the rate of
      postoperative complete heart block.
AB  - BACKGROUND: Surgical implantation of a prosthetic aortic valve is typically done
      with multiple interrupted sutures. We adapted a running suture line technique for
      prostheses implantation to decrease the rate of complete heart block
      necessitating permanent pacemaker. METHODS: 374 patients undergoing isolated
      aortic valve replacements were identified between 2015 and 2017. Patients with
      preoperative heart block, patients undergoing concomitant MAZE procedure and
      those undergoing multivalve procedures were excluded. Interrupted technique was
      performed with multiple non-pledgeted sutures. Running technique was performed
      with three 2-0 polypropylene sutures. Propensity-score matching (caliper distance
      = 0.10) was used to match based on patient age, gender, BMI, diabetes mellitus,
      renal failure, heart failure, arrythmias, use of anti-arrhythmics, and STS PROM.
      RESULTS: Propensity score matching yielded 103 pairs of running technique and
      interrupted technique patients for analysis. Within the propensity score-matched
      cohort, there were no differences in sustained complete heart block and need for
      pacemaker, 4 (3.8%) for running technique vs 3 (2.9%) for interrupted technique
      (p = 0.307). At 4 weeks, there was no difference in mean prosthetic aortic valve
      gradients calculated on transthoracic echocardiogram (6.39 +/- 2.47 mmHg vs 6.46
      +/- 2.86, p = 0.850). There was no difference in paravalvular leak (0 (0%) vs 2
      (1.9%), p = 0.070). CONCLUSIONS: Surgical implantation of a prosthetic aortic
      valve may be performed with a running suture technique without any significant
      increase in risk of heart block, need for permanent pacemaker or paravalvular
      leak. Long-term data will be critical to evaluate any development of paravalvular
      leaks in the future.

PMID- 30209775
TI  - Retinal function in eyes with proliferative diabetic retinopathy treated with
      intravitreal ranibizumab and multispot laser panretinal photocoagulation.
AB  - PURPOSE: To compare retinal function changes in eyes with proliferative diabetic
      retinopathy (PDR) after intravitreal ranibizumab (IVR), combined or not with
      conventional (ETDRS) or multispot laser panretinal (PASCAL) photocoagulation
      (PRP). METHODS: This study included laser-naive PDR patients that required PRP.
      Eyes were randomly and prospectively assigned to receive IVR or IVR combined with
      PASCAL or EDTRS. PRP was performed at baseline in 1 (PASCAL) or 2 (ETDRS)
      sessions. In eyes with macular edema, macular short pulse grid laser was
      associated with IVR at baseline and IVR was repeated monthly or quarterly if
      neovascularization was detected on angiography. Comprehensive ophthalmological
      evaluations, including SD-OCT, were performed at baseline and every 4 weeks after
      treatment. Full-field electroretinography (ERG: extended ISCEV standard) was
      performed at baseline and at 12, 24 and 48 weeks. RESULTS: IVR = 13, PASCAL = 15
      and ETDRS = 15 eyes finished 48-week follow-up. There was a statistically
      significant BCVA improvement of 0.1-0.3 logMAR in all groups, and fluorescein
      angiography leakage area (FLA) reduced in 56%, 73%, and 73% from baseline for
      ETDRS, IVR and PASCAL, respectively, up to 48 weeks without significant
      differences between groups (p > 0.05). A significant a- and b-wave amplitudes
      reduction was observed for dark- and light-adapted ERG for ETDRS and PASCAL, but
      only minor dark-adapted b-wave reduction was found for IVR, up to 48 weeks. As an
      example, at week 48, combined response b-wave amplitude reduced in 181.5 +/- 31.4
      uV, 128.0 +/- 27.9 uV and 82.4 +/- 15.2 uV for ETDRS, PASCAL and IVR (p < 0.05
      each group), respectively. No significant difference was observed between ETDRS
      and PASCAL for any ERG parameter. CONCLUSIONS: IVR combined with single or
      multiple spot PRP causes similar retinal function impairment during 48 weeks of
      observation, while IVR alone seems to be similarly effective controlling FLA
      without changing retinal function.

PMID- 30209777
TI  - Mid-term outcomes of mechanical pulmonary valve replacement: a single
      institutional experience of 396 patients.
AB  - OBJECTIVES: Previous small-sized studies have demonstrated the safety and
      efficacy of mechanical pulmonary valve replacement (mPVR) in patients with
      congenital heart disease; however, the predictors of major complications and
      reoperation remained unclear. METHODS: In a retrospective study, we reported the
      mid-term outcomes of a large-scaled series of patients, 396 patients, with
      congenital heart diseases who underwent mPVR in a single institution. RESULTS:
      The patients' mean age at mPVR was 24.3 +/- 9 years (4-58 years). Most patients
      (84.3%) underwent tetralogy of Fallot total correction. The median of follow-up
      was 36 months (24-49 months). Prosthetic valve malfunction caused by thrombosis
      or pannus formation developed in 12.1% of patients during follow-up period.
      Reoperation was performed in 7 cases with pannus formation and 6 cases with
      mechanical valve thrombosis. Freedom from reoperation at 1, 5, and 10 years was
      99%, 97%, and 96%, respectively. Neither early nor mid-term mortalities were
      detected. Cox regression models showed that male gender and smaller valve size
      increased the risk of prosthetic valve failure. The age at mPVR, interval between
      congenital heart defect repair and mPVR, and concomitant procedures predicted
      reoperation. In multivariate analysis, younger age and the interval between first
      operation and mPVR predicted reoperation either. CONCLUSIONS: The success rate of
      mPVR is excellent in mid-term follow-up. Younger age, longer interval between the
      repair of congenital defect and mPVR, and cooperation increased reoperation risk.
      However, strict adherence to life-long anticoagulation regimen and patient
      selection are of great importance for the implementation of mPVR.

PMID- 30209779
TI  - Vitamin D and health in the Mediterranean countries.
AB  - Vitamin D, traditionally well known for its role in maintaining optimal health
      through its contribution to calcium metabolism and skeletal health, has received
      increased attention over the past two decades, with considerable focus being
      placed on its nonskeletal benefits. This paper is a narrative review of the
      nonskeletal health benefits of vitamin D, of particular interest to inhabitants
      of Mediterranean countries, namely, autism, cancer, cardiovascular disease,
      chronic obstructive pulmonary disease, dental caries, diabetes mellitus, erectile
      dysfunction, hypertension, metabolic syndrome, respiratory tract infections, all
      cause mortality, and pregnancy and birth outcomes, because of the relatively high
      incidence and/or prevalence of these disorders in this region. Currently, the
      best evidence is coming out of observational studies related to serum 25
      hydroxyvitamin D [25(OH)D] concentrations. Vitamin D clinical trials have
      generally been poorly designed and conducted, usually being based on vitamin D
      dose rather than 25(OH)D concentration. The optimal 25(OH)D concentration is
      above 75 nmol/l (30 ng/ml), with even better health outcomes in the range of 100
      150 nmol/l. Achieving these concentrations with vitamin D3 supplements will
      require 1000-4000 IU/day of vitamin D3. Sensible sun exposure should also be
      encouraged. Countries should also consider fortifying grain and dairy products
      with vitamin D3.

PMID- 30209778
TI  - Dietary practices and inflammatory bowel disease.
AB  - The etiology of inflammatory bowel disease (IBD) remains elusive but it is
      believed to result from incompletely understood interactions between
      environmental triggers in a potentially genetically susceptible host and a
      subsequent aberrant immune response. Its incidence is increasing worldwide at an
      unprecedented rate, outpacing what genetic influences alone could instigate. The
      increasingly integral role played by eating in social life has led patients to
      gravitate to diet and food in their consultations with physicians and other
      health care professionals, in an attempt to improve, control, or even "cure" IBD
      through diet. Diet is a modifiable factor, and both patients and healthcare
      professionals have fuelled resurgent interest in the role of diet in maintaining
      IBD remission. Despite significant and increasing interest, there is a lack of
      credible evidence to support dietary modification or restrictions to prevent
      relapse of IBD. However, recent studies have shown that more than half of the
      patients believe that diet plays an important role in triggering relapse, leading
      to self-imposed dietary restrictions, some of which can have adverse
      consequences. This underpins the need for physicians and health care
      professionals to have a better understanding of dietary practices, in triggering,
      perpetuating, and improving IBD. This review examines and discusses the evidence
      behind this.

PMID- 30209781
TI  - I-Cell Disease (Mucolipidosis II): A Case Series from a Tertiary Paediatric
      Centre Reviewing the Airway and Respiratory Consequences of the Disease.
AB  - BACKGROUND: Inclusion cell disease (I-cell) is a rare autosomal recessive
      metabolic disease involving multiple organ systems, associated with a severely
      restricted life expectancy. No curative therapy is currently available, with
      management aimed at symptom palliation. METHODS: We present a retrospective,
      single-centre, case series of children referred to a tertiary paediatric
      metabolic service. The clinical presentation, demographics, genetics and natural
      history of the condition are investigated. RESULTS: Five patients with I-cell
      disease were referred over a 10-year period. All patients were born with
      dysmorphic features and had a family history of I-cell disease on further
      exploration. Phenotypic variation was seen within patients with the same genetic
      profile. Airway problems were common with 100% of the documented sleep oximetry
      studies suggesting sleep-disordered breathing. Of the two patients who had
      tracheal intubation anaesthetic difficulties we encountered, one required
      intraoperative reintubation, and one suffered a failed intubation with subsequent
      death. All five patients required oxygen therapy with the use of CPAP and BiPAP
      also seen. Feeding issues were almost universal with four of the five patients
      requiring nasogastric feeding. Four patients had died in the 10-year period with
      a mean life expectancy of 36 months. Cause of death for three of the four
      patients was respiratory failure. CONCLUSIONS: Airway problems, including sleep
      disordered breathing, were ubiquitous in this cohort of children. Any
      intervention requiring a general anaesthetic needs careful multidisciplinary
      consideration due to significant associated risks and possibly death. Management
      as a result is generally non-surgical and symptomatic. This case series
      demonstrates universal involvement of the airway and respiratory systems, an
      important consideration when selecting meaningful outcomes for future
      effectiveness studies of novel therapies.

PMID- 30209780
TI  - First Nations Elders' perspectives of engagement in community programs in
      Nak'azdli Whut'en, British Columbia, Canada.
AB  - OBJECTIVES: Meaningful social engagement is important to reduce risk for social
      isolation and loneliness. First Nations Elders are a unique group and little
      knowledge currently exists of their preferred forms of social interaction. The
      objective of this study was to describe the types of programs Nak'azdli Elders
      desire, identify barriers to participation, and improve creation of programs that
      address Elders' needs and interests. METHODS: This project was co-created by the
      Nak'azdli Health Centre and Elders, located in Northern British Columbia, with
      support from academic partners when and where asked. An advisory committee
      selected participants perceived as able to complete the survey and available for
      interviewing. Participants were interviewed orally in English or Carrier in their
      homes or at a drop-in centre, by a well-respected Nak'azdli Elder. The Elder
      entered participant responses (including self-reported health, awareness and
      utilization for existing programs, and preferences for new programs) into a paper
      based survey. Descriptive and content analysis were conducted. RESULTS: Nak'azdli
      Elders (N = 38) were interested in wisdom sharing, social programs, and health
      related activities. Elders wanted to be actively engaged in programs/activity
      selection, helping organize programs, knowledge sharing, skills, and stories.
      Barriers to participation included lack of transportation, personal health
      concerns, scheduling conflicts, and lack of knowledge about programs/activities.
      CONCLUSION: Nak'azdli Elders were interested in culturally relevant programs
      involving sharing cultural knowledge, teachings, and/or language with younger
      generations. Elders wanted to be engaged in all stages of activities, including
      planning, participation, and evaluation. Future programs should prioritize
      community collaboration and co-creation with Elders.

PMID- 30209782
TI  - Oral Ganglioside Supplement Improves Growth and Development in Patients with
      Ganglioside GM3 Synthase Deficiency.
AB  - Ganglioside GM3 synthase is a key enzyme involved in the biosynthesis of
      gangliosides. GM3 synthase deficiency (GM3D) causes an absence of GM3 and all
      downstream biosynthetic derivatives. The affected individuals manifest with
      severe irritability, intractable seizures, and profound intellectual disability.
      The current study is to assess the effects of an oral ganglioside supplement to
      patients with GM3D, particularly on their growth and development during early
      childhood. A total of 13 young children, 11 of them under 40 months old, received
      oral ganglioside supplement through a dairy product enriched in gangliosides, for
      an average of 34 months. Clinical improvements were observed in most children
      soon after the supplement was initiated. Significantly improved growth and
      development were documented in these subjects as average percentiles for weight,
      height, and occipitofrontal circumference increased in 1-2 months. Three children
      with initial microcephaly demonstrated significant catch-up head growth and
      became normocephalic. We also illustrated brief improvements in developmental and
      cognitive scores, particularly in communication and socialization domains through
      Vineland-II. However, all improvements seemed transient and gradually phased out
      after 12 months of supplementation. Gangliosides GM1 and GM3, although
      measureable in plasma during the study, were not significantly changed with
      ganglioside supplementation for up to 30 months. We speculate that the downstream
      metabolism of ganglioside biosynthesis is fairly active and the potential need
      for gangliosides in the human body is likely substantial. As we search for new
      effective therapies for GM3D, approaches to reestablish endogenous ganglioside
      supplies in the affected individuals should be considered.

PMID- 30209784
TI  - Time to recovery after general anesthesia at hospitals with and without a phase I
      post-anesthesia care unit: a historical cohort study.
AB  - PURPOSE: There is little knowledge about how hospitals can best handle
      disruptions that reduce post-anesthesia care unit (PACU) capacity. Few hospitals
      in Japan have any PACU beds and instead have the anesthesiologists recover their
      patients in the operating room. We compared postoperative recovery times between
      a hospital with (University of Iowa) and without (Shin-yurigaoka General
      Hospital) a PACU. METHODS: This historical cohort study included 16 successive
      patients undergoing laparoscopic gynecologic surgery with endotracheal intubation
      for general anesthesia, at each of the hospitals, and with the hours from OR
      entrance until the last surgical dressing applied >= two hours. Postoperative
      recovery times, defined as the end of surgery until leaving for the surgical
      ward, were compared between the hospitals. RESULTS: The median [interquartile
      range] of recovery times was 112 [94-140] min at the University of Iowa and 22
      [18-29] min at the Shin-yurigaoka General Hospital. Every studied patient at the
      University of Iowa had a longer recovery time than every such patient at Shin
      yurigaoka General Hospital (Wilcoxon-Mann-Whitney, P < 0.001). The ratio of the
      mean recovery times was 4.90 (95% confidence interval [CI], 4.05 to 5.91; P <
      0.001) and remained comparable after controlling for surgical duration (5.33; 95%
      CI, 3.66 to 7.76; P < 0.001). The anesthetics used in the Iowa hospital were a
      volatile agent, hydromorphone, ketorolac, and neostigmine compared with the
      Japanese hospital where bispectral index monitoring and target-controlled
      infusions of propofol, remifentanil, acetaminophen, and sugammadex were used.
      CONCLUSIONS: This knowledge can be generally applied in situations at hospitals
      with regular PACU use when there are such large disruptions to PACU capacity that
      it is known before a case begins that the anesthesiologist likely will need to
      recover the patient (i.e., when there will not be an available PACU bed and/or
      nurse). The Japanese anesthesiologists have no PACU labour costs but likely
      greater anesthesia drug/monitor costs.

PMID- 30209783
TI  - Matrine promotes liver cancer cell apoptosis by inhibiting mitophagy and
      PINK1/Parkin pathways.
AB  - Matrine is a natural alkaloid isolated from the root and stem of the legume plant
      Sophora. Its anti-proliferative and pro-apoptotic effects on several types of
      cancer have been well-documented. However, the role of matrine in regulating
      mitochondrial homeostasis, particularly mitophagy in liver cancer apoptosis,
      remains uncertain. The aim of our study was to explore whether matrine promotes
      liver cancer cell apoptosis by modifying mitophagy. HepG2 cells were used in the
      study and treated with different doses of matrine. Cell viability and apoptosis
      were determined by MTT assay, TUNEL staining, western blotting, and LDH release
      assay. Mitophagy was monitored by immunofluorescence assay and western blotting.
      Mitochondrial function was assessed by immunofluorescence assay, ELISA, and
      western blotting. The results of our study indicated that matrine treatment dose
      dependently reduced cell viability and increased the apoptotic rate of HepG2
      cells. Functional studies demonstrated that matrine treatment induced
      mitochondrial dysfunction and activated mitochondrial apoptosis by inhibiting
      protective mitophagy. Re-activation of mitophagy abolished the pro-apoptotic
      effects of matrine on HepG2 cells. Molecular investigations further confirmed
      that matrine regulated mitophagy via the PINK1/Parkin pathways. Matrine blocked
      the PINK1/Parkin pathways and repressed mitophagy, whereas activation of the
      PINK1/Parkin pathways increased mitophagy activity and promoted HepG2 cell
      survival in the presence of matrine. Together, our data indicated that matrine
      promoted HepG2 cell apoptosis through a novel mechanism that acted via inhibiting
      mitophagy and the PINK1/Parkin pathways. This finding provides new insight into
      the molecular mechanism of matrine for treating liver cancer and offers a
      potential target to repress liver cancer progression by modulating mitophagy and
      the PINK1/Parkin pathways.

PMID- 30209785
TI  - Latent class analysis stratifies mortality risk in patients developing acute
      kidney injury after high-risk intraabdominal general surgery: a historical cohort
      study.
AB  - PURPOSE: Risk stratification for postoperative acute kidney injury (AKI)
      evaluates a patient's risk for developing this complication using preoperative
      characteristics. Nevertheless, it is unclear if these characteristics are also
      associated with mortality in patients who actually develop this complication, so
      we aimed to determine these associations. METHODS: The 2011-15 American College
      of Surgeons National Surgical Quality Improvement Program was used to obtain a
      historical, observational cohort of high-risk intraabdominal general surgery
      patients with AKI, which was defined as an increase in serum creatinine > 177
      umol.L-1 (2 mg.dL-1) above the preoperative value and/or the need for dialysis.
      Latent class analysis, a model-based clustering technique, classified patients
      based on preoperative comorbidities and risk factors. The associations between
      the latent classes and the time course of AKI development and mortality after AKI
      were assessed with the Kruskall-Wallis test and Cox models. RESULTS: A seven
      class model was fit on 3,939 observations (derivation cohort). Two patterns for
      the time course of AKI diagnosis emerged: an "early" group (median [interquartile
      range] day of diagnosis 3 [1-10]) and a "late" group (day 9 [3-16]). Three
      patterns of survival after AKI diagnosis were identified (groups A-C). Compared
      with the group with the lowest mortality risk (group A), the hazard ratios (95%
      confidence intervals) for 30-day mortality were 1.79 [1.55 to 2.08] for group B
      and 3.55 [3.06 to 4.13] for group C. These differences in relative hazard were
      similar after adjusting for the postoperative day of AKI diagnosis and surgical
      procedure category. CONCLUSIONS: Among patients with AKI after high-risk general
      surgery, the preoperative comorbid state is associated with the time course of
      and survival after AKI. This knowledge can stratify mortality risk in patients
      who develop postoperative AKI.

PMID- 30209786
TI  - Associations of brain entropy (BEN) to cerebral blood flow and fractional
      amplitude of low-frequency fluctuations in the resting brain.
AB  - Entropy is a fundamental trait of human brain. Using fMRI-based brain entropy
      (BEN) mapping, interesting findings have been increasingly revealed in normal
      brain and neuropsychiatric disorders. As BEN is still relatively new, an often
      raised question is how much new information can this measure tell about the brain
      compared to other more established brain activity measures. The study aimed to
      address that question by examining the relationship between BEN and cerebral
      blood flow (CBF) and the fractional amplitude of low-frequency fluctuations
      (fALFF), two widely used resting state brain state measures. fMRI data acquired
      from a large cohort of normal subjects were used to calculate the three metrics;
      inter-modality associations were assessed at each voxel through the Pearson
      correlation analysis. A moderate to high positive BEN-CBF and BEN-fALFF
      correlations were found in orbito-frontal cortex (OFC) and posterior inferior
      temporal cortex (ITC); Strong negative BEN-fALFF correlations were found in
      visual cortex (VC), anterior ITC, striatum, motor network, precuneus, and lateral
      parietal cortex. Positive CBF-fALFF correlations were found in medial OFC (MOFC),
      medial prefrontal cortex (MPFC), left angular gyrus, and left precuneus.
      Significant gender effects were observed for all three metrics and their
      correlations. Our data clearly demonstrated that BEN provides unique information
      that cannot be revealed by CBF and fALFF.

PMID- 30209787
TI  - Using pH Gradient Dissolution with In-Situ Flux Measurement to Evaluate
      Bioavailability and DDI for Formulated Poorly Soluble Drug Products.
AB  - This study described a pH-gradient dissolution method combined with flux
      measurements as an in vitro tool for assessing the risk of bioavailability
      reduction due to drug-drug interactions (DDI) caused by acid reducing agents
      (ARAs). The device incorporates absorption chambers into USP II dissolution
      vessels, with fiber optic UV-probes monitoring concentration in situ. Dosage
      forms of Genentech BCS class II drugs, GDC-0810, GDC-0941, and compound A, were
      tested by starting the dissolution in either pH 1.6 or pH 4.0 media then
      converting to FaSSIF after 30 min. GDC-0810 showed no significant difference in
      flux between the two conversion experiments. A supersaturation phase was observed
      for GDC-0941 in the pH 1.6 experiments after media conversion to FaSSIF; however,
      it did not appear to occur in the pH 4.0 experiment due to low drug solubility at
      pH 4.0, resulting in a 95% decrease in flux compared to pH 1.6 experiment. The
      extent of flux reduction and the total accumulated API mass in the absorption
      chamber agreed well with the 89% reduction in mean Cmax and the 82% reduction in
      mean AUC from dog PK study between animals treated with pentagastrin and
      famotidine. Testing of the compound A optimized formulation tablets showed a 25%
      reduction in flux and in vitro absorbed amount by changing pH 1.6 to 4.0,
      correlating well with the AUC decrease in clinical studies. Good correlation
      between in vitro data and in vivo PK data demonstrated the applicability of the
      method for formulators to develop drug products mitigating DDI from ARAs.

PMID- 30209788
TI  - Lipid Architectonics for Superior Oral Bioavailability of Nelfinavir Mesylate:
      Comparative in vitro and in vivo Assessment.
AB  - Nelfinavir mesylate (NFV), a human immunodeficiency virus (HIV) protease
      inhibitor, is an integral component of highly active anti retro viral therapy
      (HAART) for management of AIDS. NFV possesses pH-dependent solubility and has low
      and variable bioavailability hampering its use in therapeutics. Lipid-based
      particulates have shown to improve solubility of poorly water soluble drugs and
      oral absorption, thereby aiding in improved bioavailability. The current study
      compares potential of vesicular and solid lipid nanocarriers of NFV with drug
      nanocrystallites and microvesicular systems like cochleates in improving
      bioavailability of NFV. The paper outlines investigation of systems using in
      vitro models like in vitro lipolysis, in vitro release, and permeation through
      cell lines to predict the in vivo potential of nanocarriers. Finally, in vivo
      pharmacokinetic study is reported which provided proof of concept in sync with
      results from in vitro studies. Graphical Abstract ?.

PMID- 30209789
TI  - Novel Self-Assembled Ibrutinib-Phospholipid Complex for Potently Peroral Delivery
      of Poorly Soluble Drugs with pH-Dependent Solubility.
AB  - As an irreversible small-molecule kinase inhibitor, ibrutinib (IBR) exhibits
      excellent tumor suppression in various tumor cells. However, IBR is insoluble at
      neutral pH and can dissolve only at low pH: thus, commercial IBR products present
      poor bioavailability and weakened in vivo antitumor activity. Therefore, we aimed
      to develop a stable IBR-phospholipid complex (IBR-PC) using egg
      phosphatidylglycerol (EPG) as excipients to improve the bioavailability of IBR
      and further enhance its antitumor effects. IBR-PC was characterized by
      transmission electron microscopy (TEM), Fourier transform infrared spectroscopy
      (FT-IR), differential scanning calorimetry (DSC), X-ray powder diffraction
      (XPRD), and molecular docking and simulation test, which all explained the
      interactions of two components. Solubility tests demonstrate that the novel
      formulation can maintain excellent solubility (above 5 mg/mL) at various pH
      levels. Storage stability tests show that no change in particle size or content
      of IBR-PC was observed during the experimental period. In vivo pharmacokinetic
      results demonstrated that the relative bioavailability of IBR-PC was a 9.14-fold
      improvement relative to that of IBR suspension (IBR-susp). Furthermore, IBR-PC
      was associated with enhanced cytotoxic activity in vitro and superior tumor
      growth suppression in vivo compared to that resulting from the free IBR. Thus,
      the proposed IBR-PC system is a promising drug delivery system that enhances the
      oral bioavailability of IBR, resulting in its improved in vivo antitumor effect.

PMID- 30209790
TI  - Thermal Magnetic Field Activated Propolis Release From Liquid Crystalline System
      Based on Magnetic Nanoparticles.
AB  - Intra-periodontal pocket drug delivery systems, such as liquid crystalline
      systems, are widely utilized improving the drug release control and the therapy.
      Propolis is used in the treatment of periodontal diseases, reducing the
      inflammatory and infectious conditions. Iron oxide magnetic nanoparticles (MNPs)
      can improve the treatment when an alternating external magnetic field (AEMF) is
      applied, increasing the local temperature. The aim of this study was to develop a
      liquid crystalline system containing MNPs for intra-periodontal pocket propolis
      release. MNPs were prepared using iron salts and the morphological, size,
      thermal, x-ray diffraction, magnetometry, and Mossbauer spectroscopy analyses
      were performed. Cytotoxicity studies using Artemia salina and fibroblasts were
      also accomplished. The systems were prepared using polyoxyethylene (10) oleyl
      ether, isopropyl myristate, purified water, and characterized by polarized
      optical microscopy, rheometry, and in vitro drug release profile using a
      periodontal pocket simulator apparatus. The antifungal activity of the systems
      was investigated against Candida spp. using an AEMF. MNPs displayed nanometric
      size, were monodisperse, and they displayed very low cytotoxicity.
      Microscopically homogeneous formulations were obtained displaying important
      physicochemical and biological properties. The system displayed prolonged release
      of propolis and important in vitro fungicide activity, which was increased when
      the AEMF was applied, indicating a potentially alternative therapy for the
      treatment of the periodontal disease.

PMID- 30209791
TI  - A Simple and Rapid Method for Deposition and Measurement of Drug Transport Across
      Air Interface Respiratory Epithelia.
AB  - The purpose of this study was to present a novel and simple drug deposition
      method to evaluate drug transport of aerosol microparticles across airway
      epithelial cells. Microparticles containing ciprofloxacin HCl (Cip) and
      doxycycline (Dox), alone or in a 50:50% w/w ratio, were spray dried and suspended
      using 2H, 3H-perfluoropentane, model propellant. The suspension was then used to
      assess deposition, and transport of these drug microparticles across sub
      bronchial epithelial Calu-3 cells was also studied. In comparison with other
      methods of depositing microparticles, this proposed method, using drug suspended
      in HPFP, provides control over the amount of drugs applied on the surface of the
      cells. Therefore, cell permeability studies could be conducted with considerably
      smaller and more reproducible doses, without the physicochemical characteristics
      of the drugs being compromised or the use of modified pharmacopeia impactors. The
      suspension of microparticles in HPFP as presented in this study has provided a
      non-toxic, simple, and reproducible novel method to deliver and study the
      permeability of specific quantity of drugs across respiratory epithelial cells in
      vitro.

PMID- 30209793
TI  - Intestinal Absorption of Isoalantolactone and Alantolactone, Two Sesquiterpene
      Lactones from Radix Inulae, Using Caco-2 Cells.
AB  - BACKGROUND: Isoalantolactone and alantolactone are the main sesquiterpene
      lactones in Radix Inulae (dried root of Inula helenium L. or I. racemosa Hook.
      F.), which is a frequently utilized herbal medicine. They also occur in several
      plants and have various pharmacologic effects. However, they have been found to
      have poor oral bioavailability in rats. OBJECTIVES: To understand the intestinal
      absorptive characteristics of isoalantolactone and alantolactone as well specific
      influx and efflux transporters in their absorption. METHODS: Bidirectional
      permeabilities of isoalantolactone and alantolactone were investigated across
      Caco-2 cell monolayers. Transport assays were performed using different
      concentrations of two lactones and specific inhibitors of ATP-binding cassette
      transporters and influx transporters. RESULTS: The absorption permeability of
      isoalantolactone and alantolactone was high at the tested concentrations (5, 20
      and 80 MUmol/l), and the major permeation mechanism of both lactones was found to
      be passive diffusion with active efflux mediated by multidrug resistance
      associated proteins (MRPs) and breast cancer resistance protein (BCRP).
      CONCLUSION: Our results demonstrated that the absorption permeability of
      isoalantolactone and alantolactone was good in the Caco-2 cell model. The
      isoalantolactone and alantolactone absorption elucidated in this study provides
      useful information for further pharmacokinetics studies. Since low intestinal
      absorption can now be ruled out as a cause, further studies are needed to explain
      the low oral bioavailability of the two sesquiterpene lactones.

PMID- 30209794
TI  - Pharmacokinetics and Bioavailability Enhancement of Baicalin: A Review.
AB  - Baicalin is one of the major bioactive components of Scutellaria radix, a Chinese
      herb that has been used since ancient times. Baicalin has various pharmacological
      activities, including antitumor, antimicrobial, and antioxidant, and has wide
      clinical applications. Baicalin displays a distinct pharmacokinetic profile
      including gastrointestinal hydrolysis, enterohepatic recycling, carrier-mediated
      transport, and complicated metabolism. The in vivo disposition of baicalin is
      affected by combinations of other herbs and baicalin can interact with other co
      administered drugs due to competition between metabolic enzymes and protein
      binding. Furthermore, baicalin exhibits altered pharmacokinetic properties under
      different pathological conditions. Due to its low bioavailability, emerging novel
      baicalin preparations including nano/micro-scale baicalin delivery systems show
      better absorption and higher bioavailability in preclinical studies, and show
      promise for future clinical applications. Thus, this current review offers a
      comprehensive report on the pharmacokinetic behavior of baicalin and strategies
      to improve its bioavailability.

PMID- 30209795
TI  - Pleiotropic effects of moonlighting glyceraldehyde-3-phosphate dehydrogenase
      (GAPDH) in cancer progression, invasiveness, and metastases.
AB  - Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) may represent the quintessential
      example of a moonlighting protein. The latter are a new, intriguing class of cell
      proteins which exhibit multiple activities in different subcellular locales apart
      from their initially, well-characterized function. As such, apart from its
      classical role in energy production, membrane-bound GAPDH is required for
      membrane fusion, endocytosis and, intriguingly, for iron transport. Cytoplasmic
      GAPDH regulates mRNA stability and is required for ER to Golgi trafficking.
      Nuclear GAPDH is involved in apoptosis, transcriptional gene regulation, the
      maintenance of DNA integrity, as well as nuclear tRNA export. Paradoxically, the
      etiology of a number of human pathologies is dependent upon GAPDH structure and
      function. In particular, recent evidence indicates a significant role for
      moonlighting GAPDH in tumorigenesis. Specifically, these include its role in the
      survival of tumor cells, in tumor angiogenesis, as well as its control of tumor
      cell gene expression and posttranscriptional regulation of tumor cell mRNA. Each
      of these activities correlates with increased tumor progression and,
      unfortunately, a poor prognosis for the afflicted individual.

PMID- 30209796
TI  - A matched cohort study of radio-chemotherapy versus radiotherapy alone in soft
      tissue sarcoma patients.
AB  - PURPOSE: Adjuvant radiotherapy is the standard postoperative treatment after
      conservative surgery in high risk soft tissue sarcoma. The role of adjuvant
      chemotherapy is still debated. Therefore, a matched cohort analysis was performed
      in high risk soft tissue patients to analyse differences in terms of clinical
      outcome and toxicity between patients treated with concomitant radio-chemotherapy
      (RTCT) and radiotherapy (RT) alone. MATERIALS AND METHODS: For each patient in RT
      group was selected a patient in the RTCT group matching for age, T stage and
      grading. Acute and late toxicity were recorded, overall survival, recurrence free
      survival and distant metastases free survival were analysed and compared between
      the two groups. RESULTS: Ninety patients were selected, half of patients
      underwent radio-chemotherapy and half received radiotherapy alone. During the
      treatment Grade 3 dermatitis was recorded in 15 (16.7%) patients, 6 (6.7%)
      patients associated chemotherapy and during follow up 12 (13.3%) patients
      developed grade 2 late fibrosis, 3 (3.3%) joint stiffness and 1 (1.1%) patient
      experienced a bone fracture. There were no differences in the rate of acute and
      late toxicity between RTCT and RT alone group. Nineteen (21.1%) patients
      developed local recurrence, overall 5-year local relapse free survival was 83%.
      There were no differences between the two groups. 29 patients developed distant
      metastases, 14 (15.6%) patients in the RTCT group and 15 (16.7%) patients in the
      RT group. The 5-year distant metastases free survival was 67%. Age > 65 years was
      the only independent factor affecting distant recurrence (HR = 5.7, 95% CI 2.7
      11.9; p = 0.001). At the time of analysis 15 (16.7%) patients were dead, 6 (6.7%)
      patients in the RTCT group and 9 (10%) patients in the RT group. 5-years overall
      survival was: 88%. At multivariate analysis age > 65 years was an independent
      prognostic factor of overall survival (HR = 3.7, 95% CI 1.2-12.1, p = 0.037).
      CONCLUSIONS: Prospective randomized studies with large size population and with
      subgroup analysis for histological subtypes are necessary to clarify the role of
      adjuvant chemotherapy in soft tissue sarcoma patients. Tailored treatment has to
      be considered in elderly soft tissue patients to guarantee a better outcome in
      this high risk and fragile population.

PMID- 30209792
TI  - Chinese Herbal Medicine Combined with Entecavir for HBeAg Positive Chronic
      Hepatitis B: Study Protocol for a Multi-Center, Double-Blind Randomized
      Controlled Trial.
AB  - BACKGROUND: The domestic prevalence of chronic hepatitis B (CHB) in China is
      7.18% in 2006, imposing great societal healthcare burdens. Nucleot(s)ide
      analogues (NUCs) anti-hepatitis B virus (HBV) therapies are widely applied
      despite the relatively low rate of seroconversion and high risk of drug-resistant
      mutation. More effective treatments for CHB deserve further explorations.
      Combined therapy of NUCs plus Chinese herbal medicine (CHM) is widely accepted in
      China, which is recognized as a prospective alternative approach. The study was
      primarily designed to confirm the hypothesis that Tiaogan-Yipi Granule (, TGYP)
      or Tiaogan-Jianpi-Jiedu Granule (, TGJPJD) plus entecavir tablet (ETV) was
      superior over ETV monotherapy in enhancing HBeAg loss rate. METHODS: The study
      was a nationwide, large-scale, multi-center, double-blind, randomized, placebo
      controlled trial with a designed duration of 108 weeks. A total of 16 hospitals
      and 596 eligible Chinese HBeAg positive CHB patients were enrolled from November
      2012 to September 2013 and randomly allocated into 2 groups in 1:1 ratio via
      central randomization system: experimental group (EG) and control group (CG).
      Subjects in EG received CM formulae (TGYP or TGJPJD, 50 g per dose, twice daily)
      plus ETV tablet (or ETV placebo) 0.5 mg per day in the first 24 weeks (stage 1),
      and CHM granule plus ETV tablet (0.5 mg per day) from week 25 to 108 (stage 2).
      Subjects in CG received CHM Granule placebo plus ETV tablet (0.5 mg per day) for
      108 weeks throughout the trial. The assessments of primary outcomes (HBV serum
      markers and HBV-DNA) were conducted by a third-party College of American
      Pathologists (CAP) qualified laboratory. Adverse effects were observed in the
      hospitals of recruitment. DISCUSSION: The study was designed to compare the
      curative effect of CM plus ETV and ETV monotherapy in respect of HBeAg loss,
      which is recognized by the European Association for the Study of the Liver as "a
      valuable endpoint". We believe this trial could provide a reliable status for
      patients' "journey" towards durable responses after treatment discontinuation.
      The trial was registered before recruitment on Chinese Clinical trial registry
      (No. ChiCTR-TRC-12002784, Version 1.0, 2015/12/23).

PMID- 30209798
TI  - Systematic Review of In Vivo Animal Models of Subarachnoid Hemorrhage: Species,
      Standard Parameters, and Outcomes.
AB  - In preclinical models, modification of experimental parameters associated with
      techniques of inducing subarachnoid hemorrhage (SAH) can greatly affect outcomes.
      To analyze how parameter choice affects the relevance and comparability of
      findings, we systematically reviewed 765 experimental studies of in vivo animal
      SAH models (2000-2014). During the last decade, we found marked increases in
      publications using smaller species and models for simulating acute events after
      SAH. Overall, the fewer types of species and models used did not correlate with
      an increased standardization in the experimental characteristics and procedures.
      However, by species, commonly applied, reliable parameters for each experimental
      SAH technique were identified in mouse, rat, rabbit, and dog models. Our findings
      can serve as a starting point for discussion toward a more uniform performance of
      SAH experiments, development of preclinical SAH common data elements, and
      establishment of standardized protocols for multicenter preclinical trials.

PMID- 30209799
TI  - Autologous bilayered self-assembled skin substitutes (SASSs) as permanent grafts:
      a case series of 14 severely burned patients indicating clinical effectiveness.
AB  - Split-thickness skin autografts (AGs) are the standard surgical treatment for
      severe burn injuries. However, the treatment of patients with substantial skin
      loss is limited by the availability of donor sites for skin harvesting. As an
      alternative to skin autografts, our research group developed autologous self
      assembled skin substitutes (SASSs), allowing the replacement of both dermis and
      epidermis in a single surgical procedure. The aim of the study was to assess the
      clinical outcome of the SASSs as a permanent coverage for full-thickness burn
      wounds. Patients were recruited through the Health Canada's Special Access
      Program. SASSs were grafted on debrided full-thickness wounds according to
      similar protocols used for AGs. The graft-take and the persistence of the SASS
      epithelium over time were evaluated. 14 patients received surgical care with
      SASSs. The mean percentage of the SASS graft-take was 98 % (standard deviation =
      5) at 5 to 7 d after surgery. SASS integrity persisted over time (average follow
      up time: 3.2 years), without noticeable deficiency in epidermal regeneration.
      Assessment of scar quality (skin elasticity, erythema, thickness) was performed
      on a subset of patients. Non-homogeneous pigmentation was noticed in several
      patients. These results indicated that the SASS allowed the successful coverage
      of full-thickness burns given its high graft-take, aesthetic outcome equivalent
      to autografting and the promotion of long-term tissue regeneration. When skin
      donor sites are in short supply, SASSs could be a valuable alternative to treat
      patients with full-thickness burns covering more than 50 % of their total body
      surface area.

PMID- 30209800
TI  - The polycystic ovary syndrome: a position statement from the Polish Society of
      Endocrinology, the Polish Society of Gynaecologists and Obstetricians, and the
      Polish Society of Gynaecological Endocrinology.
AB  - Polycystic ovary syndrome (PCOS) diagnosis and therapy still arouse a lot of
      controversy. Each year brings new information, so, having collected the
      experience of three scientific societies, we present contemporary recommendations
      concerning PCOS diagnostics and treat-ment. In adult female diagnosis, we still
      use the Rotterdam criteria, which is two out of three of the follwing
      characteristics: a) ovulation abnormality, b) clinical or biochemical
      hyperandrogenism, and c) polycystic ovaries. In the case of teenagers, diagnostic
      criteria are as follows: menstruation disturbances two years after menarche and
      clinical or biochemical hyperandrogenism. The presence of polycysti-cally
      abnormal ovaries is not necessary. The consensus paper presents the threats
      resulting from imperfect diagnostic methods applied in PCOS (hyperandrogenism
      diagnostics, ultrasound examination of ovaries). Suggested therapy includes
      personalised schemes according to the dominant PCOS phenotype, i.e. metabolic,
      hyperandrogenic, or reproductive ones.

PMID- 30209797
TI  - Metabolic Control in Type 1 Diabetes: Is Adjunctive Therapy the Way Forward?
AB  - Despite advances in insulin therapies, patients with type 1 diabetes (T1DM) have
      a shorter life span due to hyperglycaemia-induced vascular disease and
      hypoglycaemic complications secondary to insulin therapy. Restricting therapy for
      T1DM to insulin replacement is perhaps an over-simplistic approach, and we focus
      in this work on reviewing the role of adjuvant therapy in this population.
      Current data suggest that adding metformin to insulin therapy in T1DM temporarily
      lowers HbA1c and reduces weight and insulin requirements, but this treatment
      fails to show a longer-term glycaemic benefit. Agents in the sodium glucose co
      transporter-2 inhibitor (SGLT-2) class demonstrate the greatest promise in
      correcting hyperglycaemia, but there are safety concerns in relation to the risk
      of diabetic ketoacidosis. Glucagon-like peptide-1 agonists (GLP-1) show a modest
      effect on glycaemia, if any, but significantly reduce weight, which may make them
      suitable for use in overweight T1DM patients. Treatment with pramlintide is not
      widely available worldwide, although there is evidence to indicate that this
      agent reduces both HbA1c and weight in T1DM. A criticism of adjuvant studies is
      the heavy reliance on HbA1c as the primary endpoint while generally ignoring
      other glycaemic parameters. Moreover, vascular risk markers and measures of
      insulin resistance-important considerations in individuals with a longer T1DM
      duration-are yet to be fully investigated following adjuvant therapies. Finally,
      studies to date have made the assumption that T1DM patients are a homogeneous
      group of individuals who respond similarly to adjuvant therapies, which is
      unlikely to be the case. Future longer-term adjuvant studies investigating
      different glycaemic parameters, surrogate vascular markers and harder clinical
      outcomes will refine our understanding of the roles of such therapies in various
      subgroups of T1DM patients.

PMID- 30209801
TI  - Management of Prader-Willi Syndrome (PWS) in adults - what an endocrinologist
      needs to know. Recommendations of the Polish Society of Endocrinology and the
      Polish Society of Paediatric Endocrinology and Diabetology.
AB  - Prader-Willi syndrome (PWS) is a complex genetic disorder characterised by a set
      of phenotypic traits, which include infantile hypotonia, short stature, and
      morbid obesity. Over the last 12 years, visible progress has been made in medical
      care management of PWS patients in Poland. Increasing awareness of the disorder
      in neonatal and paediatric care has led to early identification of the condition
      in neonates, followed by the institution of an appropriate dietary regime,
      introduction of physiotherapy, and early-onset recombinant human growth hormone
      (rhGH) treatment. Growth hormone (GH) therapy in Poland is conducted within the
      nationwide framework of the Therapeutic Programme: "Treatment of Prader-Willi
      Syndrome". The therapeutic interventions initiated in the paediatric centres need
      to be continued in multidisciplinary adult care settings. The main aim of PWS
      clinical management in adulthood is prevention of obesity and its comor-bidities,
      treatment of hormonal disorders, mental health stabilisation, nutritional
      guidance, as well as on-going physiotherapy. Integrated multidisciplinary
      therapeutic intervention is necessary if patients with such a complex genetic
      condition as PWS are to not only achieve an average life expectancy but also to
      enjoy higher quality of life.

PMID- 30209802
TI  - A review of cardiovascular outcome trials in type 2 diabetes.
AB  - Type 2 diabetes is a complex metabolic disorder associated with a high risk of
      cardiovascular complications. In December 2008, due to concerns about the cardiac
      safety of antihyperglycaemic therapies, the Food and Drug Administration (FDA)
      published a new guidance on special requirements for the demonstration of
      cardiovascular safety for these medications. In 2012, similar recommendations
      were made for antidiabetic drug manufacturers by the European Medicines Agency
      (EMA). Since then, both FDA and EMA recommendations have been applied in
      cardiovascular outcome trials (CVOTs) for several new antihyperglycaemic drugs.
      Unlike conventional trials, CVOTs are usually placebo controlled, non-inferiority
      trials that examine the cardiovascular safety of a drug compared to standard of
      care in large cohorts of patients with high cardiovascular risk or established
      cardiovascular disease. Patients in CVOTs are also monitored for a longer
      observation period than in typical randomised controlled trials to provide data
      on long-term cardiovascular risk. To date, nine CVOTs involving patients with
      type 2 diabetes have been completed, and at least 13 are still ongoing. These
      studies focus on a variety of antihyper-glycaemic drugs, including incretin-based
      agents, sodium-glucose cotransporter 2 inhibitor (SGLT-2) inhibitors, and insulin
      formulations. This article takes a critical look at these CVOTs and summarises
      the results of the completed trials.

PMID- 30209803
TI  - Pharmacotherapy of obesity - state of the art.
AB  - Obesity, which affects about 13% of the world population, results in significant
      deterioration of health and serious clinical, mainly meta-bolic and
      cardiovascular complications. Although the basis of therapeutic treatment is
      behavioural treatment, often non-pharmacological effects do not produce the
      desired effect. Currently there are several drugs with a safe action profile that
      improve the effect of treatment (5-10% weight reduction). The aim of the paper is
      to present the potential of modern pharmacotherapy in the treatment of obesity,
      in terms of mechanism of action, efficacy, and side effects, in order to
      individualise therapy. The drugs already registered include substances with a
      variety of mechanisms of action, including phentermine, orlistat, lorcaserin, and
      liraglutide. Compounded preparations (phenter-mine/topiramate, naltrexone
      SR/bupropion SR) are also available, which, by using low doses of active
      substances, have beneficial effects while reducing side effects. In addition,
      several drugs used to treat diabetes, such as metformin, SGLT2 inhibitors, GLP-1
      agonists, and pramlintide, promote weight loss, although their use is reserved
      for diabetics, especially type 2 patients. Regarding the current alarm-ing
      epidemiological data there is a need for intensive prevention and treatment of
      obesity as well as the development of a new form of pharmacotherapy (new
      substances and treatment regimens) to develop effective, safe, and, above all,
      long-term effective therapy for the treatment of obesity.

PMID- 30209804
TI  - Blood utilization and mortality in victims of gun violence.
AB  - BACKGROUND: Blood transfusion can be lifesaving for patients with hemorrhage;
      however, transfusion requirements for victims of gun violence are poorly
      understood. STUDY DESIGN AND METHODS: In an urban, Level 1 trauma center, 23,422
      trauma patients were analyzed in a retrospective cohort study. Patients with
      gunshot wounds (GSWs) (n = 2,672; 11.4% of trauma patients) were compared to
      those with non-GSW traumatic injuries from 2005 to 2017, to assess blood
      utilization. RESULTS: The GSW cohort was approximately five times more likely to
      require transfusion (538 of 2672 [20.1%] vs. 798 of 20,750 [3.9%]; p < 0.0001),
      and the number of blood component units transfused per patient was approximately
      10 times greater (3.3 +/- 13.5 vs. 0.31 +/- 3.8 units/patient; p < 0.0001),
      compared to the non-GSW cohort. The risk-adjusted likelihood of requiring high
      dose transfusion was greater in the GSW cohort (odds ratio, 2.38; 95% confidence
      interval, 1.14-5.80), and requirements were increased for all four blood
      components (red blood cells, platelets, plasma, and cryoprecipitate). Patients
      with GSWs had approximately 14 times greater overall mortality (653 of 2672
      [24.4%] vs. 352 of 20,750 [1.7%]; p < 0.0001]. Compared to non-GSW penetrating
      injuries (e.g., stab wounds), those with GSWs had approximately four times higher
      transfusion requirements (3.3 +/- 13.5 vs. 0.80 +/- 3.8 units/patient; p <
      0.0001), and approximately eight times greater overall mortality (653 of 2672
      [24.4%] vs. 28 of 956 [2.9%]; p < 0.0001). CONCLUSIONS: Compared to other
      traumatic injuries, GSW injuries are associated with substantially greater blood
      utilization and mortality. Trauma centers treating GSW injuries should have ready
      access to all blood components and ability to implement massive transfusions.

PMID- 30209805
TI  - Mesh versus non-mesh for inguinal and femoral hernia repair.
AB  - BACKGROUND: This is an update of a Cochrane Review first published in
      2001.Hernias are protrusions of all or part of an organ through the body wall
      that normally contains it. Groin hernias include inguinal (96%) and femoral (4%)
      hernias, and are often symptomatic with discomfort. They are extremely common,
      with an estimated lifetime risk in men of 27%. Occasionally they may present as
      emergencies with complications such as bowel incarceration, obstruction and
      strangulation. The definitive treatment of all hernias is surgical repair,
      inguinal hernia repair being one of the most common surgical procedures
      performed. Mesh (hernioplasty) and the traditional non-mesh repairs
      (herniorrhaphy) are commonly used, with an increasing preference towards mesh
      repairs in high-income countries. OBJECTIVES: To evaluate the benefits and harms
      of different inguinal and femoral hernia repair techniques in adults,
      specifically comparing closure with mesh versus without mesh. Outcomes include
      hernia recurrence, complications (including neurovascular or visceral injury,
      haematoma, seroma, testicular injury, infection, postoperative pain), mortality,
      duration of operation, postoperative hospital stay and time to return to
      activities of daily living. SEARCH METHODS: We searched the following databases
      on 9 May 2018: Cochrane Colorectal Cancer Group Specialized Register, Cochrane
      Central Register of Controlled Trials (Issue 1), Ovid MEDLINE (from 1950), Ovid
      Embase (from 1974) and Web of Science (from 1900). Furthermore, we checked the
      WHO International Clinical Trials Registry Platform (ICTRP) and
      ClinicalTrials.gov for trials. We applied no language or publication
      restrictions. We also searched the reference lists of included trials and review
      articles. SELECTION CRITERIA: We included randomised controlled trials of mesh
      compared to non-mesh inguinal or femoral hernia repairs in adults over the age of
      18 years. DATA COLLECTION AND ANALYSIS: We used standard methodological
      procedures expected by Cochrane. Where available, we collected information on
      adverse effects. We presented dichotomous data as risk ratios, and where possible
      we calculated the number needed to treat for an additional beneficial outcome
      (NNTB). We presented continuous data as mean difference. Analysis of missing data
      was based on intention-to-treat principles, and we assessed heterogeneity using
      an evaluation of clinical and methodological diversity, Chi2 test and I2
      statistic. We used GRADE to assess the quality of evidence for each outcome. MAIN
      RESULTS: We included 25 studies (6293 participants) in this review. All included
      studies specified inguinal hernias, and two studies reported that femoral hernias
      were included.Mesh repair probably reduces the risk of hernia recurrence compared
      to non-mesh repair (21 studies, 5575 participants; RR 0.46, 95% CI 0.26 to 0.80,
      I2 = 44%, moderate-quality evidence). In absolute numbers, one hernia recurrence
      was prevented for every 46 mesh repairs compared with non-mesh repairs. Twenty
      four studies (6293 participants) assessed a wide range of complications with
      varying follow-up times. Neurovascular and visceral injuries were more common in
      non-mesh repair groups (RR 0.61, 95% CI 0.49 to 0.76, I2 = 0%, NNTB = 22, high
      quality evidence). Wound infection was found slightly more commonly in the mesh
      group (20 studies, 4540 participants; RR 1.29, 95% CI 0.89 to 1.86, I2 = 0%, NNTB
      = 200, low-quality evidence). Mesh repair reduced the risk of haematoma compared
      to non-mesh repair (15 studies, 3773 participants; RR 0.88, 95% CI 0.68 to 1.13,
      I2 = 0%, NNTB = 143, low-quality evidence). Seromas probably occur more
      frequently with mesh repair than with non-mesh repair (14 studies, 2640
      participants; RR 1.63, 95% CI 1.03 to 2.59, I2 = 0%, NNTB = 72, moderate-quality
      evidence), as does wound swelling (two studies, 388 participants; RR 4.56, 95% CI
      1.02 to 20.48, I2 = 33%, NNTB = 72, moderate-quality evidence). The comparative
      effect on wound dehiscence is uncertain due to wide confidence intervals (two
      studies, 329 participants; RR 0.55, 95% CI 0.12 to 2.48, I2 = 37% NNTB = 77, low
      quality evidence). Testicular complications showed nearly equivocal results; they
      probably occurred slightly more often in the mesh group however the confidence
      interval around the effect was wide (14 studies, 3741 participants; RR 1.06, 95%
      CI 0.63 to 1.76, I2 = 0%, NNTB = 2000, low-quality evidence). Mesh reduced the
      risk of postoperative urinary retention compared to non-mesh (eight studies, 1539
      participants; RR 0.53, 95% CI 0.38 to 0.73, I2 = 56%, NNTB = 16, moderate-quality
      evidence).Postoperative and chronic pain could not be compared due to variations
      in measurement methods and follow-up time (low-quality evidence).No deaths
      occurred during the follow-up periods reported in the seven studies (2546
      participants) reporting this outcome (high-quality evidence).The average
      operating time was longer for non-mesh repairs by a mean of 4 minutes 22 seconds,
      despite wide variation across the studies regarding size and direction of effect,
      thus this result is uncertain (20 studies, 4148 participants; 95% CI -6.85 to 
      1.60, I2= 97%, very low-quality evidence). Hospital stay may be shorter with mesh
      repair, by 0.6 days (12 studies, 2966 participants; 95% CI -0.86 to -0.34, I2 =
      98%, low-quality evidence), and participants undergoing mesh repairs may return
      to normal activities of daily living a mean of 2.87 days sooner than those with
      non-mesh repair (10 studies, 3183 participants; 95% CI -4.42 to -1.32, I2 = 96%,
      low-quality evidence), although the results of both these outcomes are also
      limited by wide variation in the size and direction of effect across the studies.
      AUTHORS' CONCLUSIONS: Mesh and non-mesh repairs are effective surgical approaches
      in treating hernias, each demonstrating benefits in different areas. Compared to
      non-mesh repairs, mesh repairs probably reduce the rate of hernia recurrence, and
      reduce visceral or neurovascular injuries, making mesh repair a common repair
      approach. Mesh repairs may result in a reduced length of hospital stay and time
      to return to activities of daily living, but these results are uncertain due to
      variation in the results of the studies. Non-mesh repair is less likely to cause
      seroma formation and has been favoured in low-income countries due to low cost
      and reduced availability of mesh materials. Risk of bias in the included studies
      was low to moderate and generally handled well by study authors, with attention
      to details of allocation, blinding, attrition and reporting.

PMID- 30209806
TI  - Strategies to reduce and maintain low perinatal mortality in resource-poor
      settings - Findings from a four-decade observational study of birth records from
      a large public maternity hospital in Papua New Guinea.
AB  - BACKGROUND: In many low- to middle-income countries (LMIC) assisted vaginal birth
      rates have fallen, while caesarean section (CS) rates have increased, with
      potentially deleterious consequences for maternal and perinatal mortality. AIMS:
      To review birth mode and perinatal mortality in a large LMIC hospital with strict
      labour management protocols and expertise in vacuum extraction. MATERIALS AND
      METHODS: We conducted a retrospective observational study at Port Moresby General
      Hospital in Papua New Guinea. Birth registers from 1977 to 2015 (39 years) were
      reviewed. Overall and modified (fresh stillbirths and early neonatal deaths >=500
      g) perinatal mortality rates (PMRs) were calculated by birthweight/birth mode.
      RESULTS: There were 365 056 births (5215 in 1977; 14 927 in 2015), of which 14
      179 (3.9%) were vacuum extractions, 609 (0.2%) forceps births and 14 747 (4.4%)
      CS (increase from 2% to 5%). The failure rate of vacuum extraction was 2.5%
      (range 0.5-5.4%). Symphysiotomy was employed for 184 births. From 1989 to 2015,
      the modified mean PMR for babies >=2500 g was 8.1/1000 births (range 5.6-12.1;
      6.9 in 2015), 9.1/1000 for babies >=1500 g (7.3-14.8; 9.1 in 2015) and 7.5/1000
      (0-21.7; 9.0 in 2015) for vacuum extractions (98% were >=2500 g). The overall PMR
      for these years was 29.7/1000 births. CONCLUSIONS: In an LMIC with rapidly
      increasing birth numbers a comparatively low PMR can be achieved while
      maintaining low CS rates. This may be in part accomplished through strict use of
      second-stage protocols, perinatal audit, and supportive training that promotes
      judicious and proficient use of vacuum extraction and CS.

PMID- 30209807
TI  - The addition of metronomic chemotherapy does not improve outcome for canine
      splenic haemangiosarcoma.
AB  - OBJECTIVES: To determine whether the addition of metronomic chemotherapy improved
      outcome for dogs with splenic haemangiosarcoma treated with splenectomy and
      adjuvant maximum tolerated dose chemotherapy. MATERIALS AND METHODS: Medical
      records were examined retrospectively for dogs with splenic haemangiosarcoma that
      had undergone splenectomy followed by anthracycline-based chemotherapy. Thirty
      nine dogs underwent splenectomy followed by maximum tolerated dose chemotherapy
      with an anthracycline, cyclophosphamide, or both (Group 1). Twenty-two dogs
      underwent splenectomy followed by adjuvant maximum tolerated dose chemotherapy
      with an anthracycline, cyclophosphamide, or both, plus metronomic chemotherapy
      (Group 2). Dogs in both groups were further separated into those treated with
      either maximum tolerated dose anthracycline or maximum tolerated dose
      anthracycline and cyclophosphamide. RESULTS: Median progression-free survival was
      165 days and median overall survival time was 180 days in Group 1. Median
      progression-free survival was 185 days and median overall survival time was 212
      days in Group 2. In both groups, the overall survival was shorter in dogs that
      had received maximum tolerated dose cyclophosphamide. CLINICAL SIGNIFICANCE: The
      addition of metronomic to maximum tolerated dose chemotherapy protocols does not
      appear to improve outcome in dogs with splenic haemangiosarcoma treated with
      splenectomy and maximum tolerated dose chemotherapy.

PMID- 30209808
TI  - Retrobulbar cellulitis and abscessation: focus on short- and long-term concurrent
      ophthalmic diseases in 41 dogs.
AB  - OBJECTIVE: To describe concurrent ophthalmic diseases in dogs with retrobulbar
      cellulitis and abscessation. MATERIALS AND METHODS: Retrospective analysis of
      clinical records of dogs with retrobulbar inflammation. RESULTS: Forty-one dogs
      were diagnosed with retrobulbar inflammation; of these, 23 presented with
      abscessation and two with zygomatic sialoadenitis. Diagnosis was based on orbital
      ultrasound, MRI, CT and cytological and microbiological examination of fluid or
      tissue samples. Management involved evacuation of fluid contents using ultrasound
      guided fine-needle aspiration via the pterygopalatine fossa or orbitotomy.
      Patients received systemic antibiotics (except for one with sialoadenitis),
      glucocorticoids, non-steroidal anti-inflammatory drugs, opioids and fluid
      therapy. At initial presentation one or more ophthalmic complications were
      reported in 19 dogs (46%) including internal ophthalmoplegia (n=5), blindness due
      to optic nerve damage (n=5), facial nerve paralysis (n=3), prolapse of the third
      eyelid gland (n=3), corneal ulceration (n=8), anterior uveitis (n=4),
      chorioretinitis (n=3), retinal detachment (n=2) and increased intraocular
      pressure (n=7). Information on ophthalmic complications after cessation of active
      inflammation was available for 33 patients. One or more concurrent disease was
      found in 10 cases (30%): in addition to persistent neurological deficits and
      third eyelid gland prolapse reported at initial presentation, visual deficits
      after retinal re-attachment (n=2), loss of corneal sensation (n=1), corneal
      oedema (n=1), corneal fibrosis (n=4), corneal lipidosis (n=1) and strabismus
      after suspected fibrosis (n=2) were diagnosed. CLINICAL SIGNIFICANCE: Ophthalmic
      complications are common in patients with retrobulbar inflammation indicating
      that these patients should undergo ophthalmic assessment and follow-up.

PMID- 30209809
TI  - New SMARCE1 variant in a patient with features overlapping with
      oculoauriculofrontonasal syndrome.

PMID- 30209810
TI  - Parental uncertainty about transferring their adolescent with congenital heart
      disease to adult care.
AB  - AIMS: To study parent's levels of uncertainty related to the transfer from
      pediatric to adult care in adolescents with congenital heart disease (CHD) and to
      identify potentially correlating factors. BACKGROUND: Parents acknowledge that
      during transition they struggle with finding ways of feeling secure in handing
      over the responsibility and letting go of control. Well-prepared and informed
      parents who feel secure are most likely better skilled to support their
      adolescent and to hand over the responsibility. DESIGN: A cross-sectional study.
      METHODS: Overall, 351 parents were included (35% response rate). Parental
      uncertainty was assessed using a Linear Analogue Scale (0-100). Data were
      collected between January - August 2016. Potential correlates were assessed using
      the readiness for transition questionnaire and sociodemographic data. RESULTS:
      The mean parental uncertainty score was 42.5. Twenty-four percent of the parents
      had a very low level of uncertainty (score 0-10) and 7% had a very high level
      (score 91-100). Overall, 26% of the mothers and 36% of the fathers indicated that
      they had not started thinking of the transfer yet. The level of uncertainty was
      negatively associated with the level of perceived overall readiness. Adolescents'
      age, sex, CHD complexity, and parental age were not related to uncertainty.
      CONCLUSION: A wide range in the levels of uncertainty was found. Parents who were
      less involved in the care, or perceived their adolescent as readier for the
      transition, felt less uncertain. Still, thirty percent of the parents had not
      started to think about the transfer to adult care.

PMID- 30209811
TI  - The nurse-patient relationship in the New Public Management era, in public home
      care: A focused ethnography.
AB  - AIM: The aim of this study was to gain deeper understandings of nurse-patient
      relationships in the New Public Management era, by exploring beliefs and
      practices of nurses and patients in Norwegian public home care. BACKGROUND:
      Organization of Norwegian home care services is based on New Public Management
      ideologies, which have led to a rigidly formalized and task-oriented nursing
      practice that may jeopardize individual nursing care. Nurse-patient relationships
      have several positive effects on patients' health and well-being, but
      organizational boundaries and time pressure affect the quality of relationships.
      DESIGN: Focused ethnography. METHODS: Data were collected between November 2015
      July 2016 using participant observation and semi-structured interviews with 10
      nurses and eight patients in six different home care areas, in two Norwegian
      municipalities. Data analysis was based on Roper and Shapiras framework.
      FINDINGS: Findings demonstrate the continued importance of nurse-patient
      relationships in contemporary home care, while identifying extensive variations
      in the degree of closeness and emotional involvement. Organizational boundaries,
      time constraints, high workload, and disharmony between nurses "competence and
      patients" complex illnesses, influence practice in ways that reduce the
      significance of nurse-patient relationships and affect conditions under which
      they develop and evolve. Facing a system nurses perceive to function suboptimal,
      they govern practices based on their own professional assessments, and findings
      indicate cultural patterns in the way both nurses and patients prioritize to
      safeguard nurse-patient relationships. CONCLUSION: Home care cultures based on
      traditional nursing values continue, despite New Public Management influences,
      but a transition into New Public Management culture may, over time, influence the
      quality of nurse-patient relationships and meanings attributed to them.

PMID- 30209812
TI  - Relative efficiency of unequal cluster sizes in stepped wedge and other trial
      designs under longitudinal or cross-sectional sampling.
AB  - BACKGROUND: A cluster trial with unequal cluster sizes often has lower precision
      than one with equal clusters, with a corresponding inflation of the design
      effect. For parallel group trials, adjustments to the design effect are available
      under sampling models with a single intracluster correlation. Design effects for
      equal clusters under more complex scenarios have appeared recently (including
      stepped wedge trials under cross-sectional or longitudinal sampling). We
      investigate the impact of unequal cluster size in these more general settings.
      RESULTS: Assuming a linear mixed model with an exchangeable correlation structure
      that incorporates cluster and subject autocorrelation, we compute the relative
      efficiency (RE) of a trial with clusters of unequal size under a size-stratified
      randomization scheme, as compared to an equal cluster trial with the same total
      number of observations. If there are no within-cluster time effects, the RE
      exceeds that for a parallel trial. In general, the RE is a weighted average of
      the RE for a parallel trial and the RE for a crossover trial in the same
      clusters. Existing approximations for parallel designs are extended to the
      general setting. Increasing the cluster size by the factor (1 + CV2 ), where CV
      is the coefficient of variation of cluster size, leads to conservative sample
      sizes, as in a popular method for parallel trials. CONCLUSION: Methods to assess
      experimental precision for single-period parallel trials with unequal cluster
      sizes can be extended to stepped wedge and other complete layouts under
      longitudinal or cross-sectional sampling. In practice, the loss of precision due
      to unequal cluster sizes is unlikely to exceed 12%.

PMID- 30209813
TI  - Author's response: When should meta-analysis avoid making hidden normality
      assumptions?

PMID- 30209814
TI  - Developing and validating learning domains, competencies, and evaluation items
      for global health clinical immersion practicums for graduate-level nursing
      programs.
AB  - AIM: To develop and validate learning domains, competencies, and evaluation tool
      for graduate-level experiential nursing global health programs. BACKGROUND:
      Standard competencies have not been synthesized and delineated nor have
      evaluation tools been developed for global health programs at the graduate level.
      DESIGN: A combination of a documentary literature review and expert consensus
      panel to validate results was used as a design for this study. METHODS: The NLM
      and CINAHL databases were searched for articles published between 2007 - 2017
      relevant to graduate-level global health nursing programs. Data were extracted
      and coded, from which themes regarding learning domains, competencies and
      evaluation items were derived. We then used a three-step expert panel to refine
      and form a statistical representation (>0.78 agreement on importance, relevance
      and clarity) of the learning domains, competencies, and evaluation items.
      RESULTS: Relevant articles (N = 26) were included for the documentary review, 18
      concerning learning domains of global health immersion programs and eight
      concerning interdisciplinary global health competencies specific to nursing.
      These learning relationships were then formatted into a table subdivided between
      learning categories for expert panel consensus. After expert panel review, a
      compendium of learning domains, competencies, and evaluation items resulted.
      CONCLUSION: Global health clinical learning practicums are essential for graduate
      level preparation of nurses. Learning domains, competencies, and evaluation tools
      need to be adopted and empirically tested by international and national nursing
      associations. The results of this study need further testing to aid these
      associations.

PMID- 30209815
TI  - Investigation of one-stage meta-analysis methods for joint longitudinal and time
      to-event data through simulation and real data application.
AB  - BACKGROUND: Joint modeling of longitudinal and time-to-event data is often
      advantageous over separate longitudinal or time-to-event analyses as it can
      account for study dropout, error in longitudinally measured covariates, and
      correlation between longitudinal and time-to-event outcomes. The current
      literature on joint modeling focuses mainly on the analysis of single studies
      with a lack of methods available for the meta-analysis of joint data from
      multiple studies. METHODS: We investigate a variety of one-stage methods for the
      meta-analysis of joint longitudinal and time-to-event outcome data. These methods
      are applied to the INDANA dataset to investigate longitudinally measured systolic
      blood pressure, with each of time to death, time to myocardial infarction, and
      time to stroke. Results are compared to separate longitudinal or time-to-event
      meta-analyses. A simulation study is conducted to contrast separate versus joint
      analyses over a range of scenarios. RESULTS: The performance of the examined one
      stage joint meta-analytic models varied. Models that accounted for between study
      heterogeneity performed better than models that ignored it. Of the examined
      methods to account for between study heterogeneity, under the examined
      association structure, fixed effect approaches appeared preferable, whereas
      methods involving a baseline hazard stratified by study were least time
      intensive. CONCLUSIONS: One-stage joint meta-analytic models that accounted for
      between study heterogeneity using a mix of fixed effects or a stratified baseline
      hazard were reliable; however, models examined that included study level random
      effects in the association structure were less reliable.

PMID- 30209816
TI  - The influence of cultural competence of nurses on patient satisfaction and the
      mediating effect of patient trust.
AB  - AIMS: To test a path model evaluating the influence of cultural competence of
      nurses on patient satisfaction and the mediating role of patient trust.
      BACKGROUND: In China, there has been an increase in medical disputes, which at
      times has resulted in physical assaults on healthcare providers. Enhanced patient
      satisfaction may reduce disputes and can perhaps be bolstered by the improved
      cultural competence of providers. DESIGN: A cross-sectional path analytic
      research design was used. METHODS: A random sample of 583 hospitalized patients
      recruited from six tertiary comprehensive hospitals in Changsha, China in 2016
      completed a face-to-face structured questionnaire. Measures included the Consumer
      Assessment of Healthcare Providers and Systems Cultural Competency Item Set, the
      Wake Forest Physician Trust Scale, the Patient Satisfaction with Primary Nurses
      Scale and the Patient Overall Satisfaction with the Hospital Scale. RESULTS:
      Significant associations among cultural competence of nurses, patient
      satisfaction and patient trust were confirmed, and path analyses supported the
      proposed mediating role of patient trust. Furthermore, the cultural competence
      subscales of communication-positive behaviours, trust-building behaviours and
      shared decision-making were positively and significantly correlated with patient
      satisfaction. CONCLUSION: Findings suggest interventions should be designed to
      improve nurse's cultural competence, especially in the domains of communication
      positive behaviours, trust-building behaviours and shared decision-making, and
      trust, to improve patient satisfaction.

PMID- 30209817
TI  - Computing individual and collective ethical utility for optimally planning phase
      III trials.
AB  - A quantitative evaluation of individual and collective ethics is proposed here,
      with the aim of providing a tool for sample size determination/estimation that
      goes further than the standard power setting of 80-90%. Individual ethics deal
      with issues that concern the patients enrolled in the trial, where collective
      ones concern the patients not enrolled in the trial, and who might benefit from a
      positive result. The global ethical utility (GEU) of a phase III trial is
      introduced here, being the summation of individual and collective ethical
      utilities, and can be viewed as a function of the sample size. The GEU model is
      based on the extent of the efficacy of the treatments in study, of the quality of
      life of the patients being treated, of the effects of potential adverse
      reactions, it accounts for the duration of the periods of interest and for the
      size of population groups, and also embeds the experimental power. This work aims
      at arguing the case for GEU adoption for sample size determination. The sample
      size that maximizes GEU can be adopted for planning the trial, even when
      providing a power value out of the classical range [.8,.9]. Alternatively, among
      the sample sizes based on power values of 80% and 90%, the one providing the
      highest GEU can be adopted. Intuitively, when a treatment is assumed to work
      well, to have few adverse effects, and is expected to improve the QoL of the ill
      population for a considerable amount of time, collective ethics may prevail
      giving ethically optimal sample sizes larger than usual, and consequent quite
      high power values (e.g. 99%). Instead, medium, though still clinically
      meaningful, levels of effect, considerable adverse reactions, and limited life
      expectation and QoL improvement, might shift the ethical balance on individual
      ethics and give an ethically optimal sample size providing a power lower than
      standard values (e.g. 70%). Some examples and an application in the
      cardiovascular area, including sensitivity analyses of the results based on the
      so-called Bayesian "assurance" technique, are also discussed. Several possible
      extensions of the model related to particular clinical frameworks are also
      presented.

PMID- 30209818
TI  - Interim monitoring using the adaptively weighted log-rank test in clinical trials
      for survival outcomes.
AB  - For testing treatment effect with survival data, the log-rank test has been the
      method of choice and enjoys an optimality property under proportional hazards
      alternatives. However, there can be significant loss of power in a variety of
      nonproportional situations. Yang and Prentice proposed an adaptively weighted log
      rank test that improves the power of the log-rank test over a wide range of
      hazard ratio scenarios. In clinical trials, the data and safety monitoring board
      typically monitors the trial results periodically. Here, we develop interim
      testing procedures for the adaptively weighted log-rank test. We establish the
      asymptotic distribution of the test statistics at the interim looks and use a
      resampling method to obtain the stopping boundaries. Through examination of the
      test behavior under local alternatives, we show that the adaptively weighted log
      rank test is fully efficient when the limiting censoring distributions in the two
      groups are equal. Unlike the case for the usual application of the log-rank test,
      critical values obtained from the resampling method are asymptotically valid
      without the assumption of equal censoring distributions in the two groups.
      Extensive simulation studies show that the new method improves the log-rank test
      for a wide range of treatment effect patterns, and that the resampling approach
      yields better control of the type 1 error rate than the originally proposed
      approach in the work of Yang and Prentice. The new procedures are illustrated in
      several clinical trial examples.

PMID- 30209820
TI  - Editorial: What are nursing journals for?

PMID- 30209819
TI  - Outcome of patients with relapsed or refractory anaplastic large cell lymphoma
      who have failed brentuximab vedotin.
AB  - Brentuximab vedotin (BV) is an anti-CD30 antibody-drug conjugate that is highly
      effective in patients with relapsed/refractory anaplastic large cell lymphoma
      (ALCL). However, survival outcomes following suboptimal response or subsequent
      relapse are not well known. We conducted a multicenter study analyzing outcomes
      of patients with relapsed/refractory ALCL who have received BV with a secondary
      focus on survival after progression following BV. A total of 56 patients were
      treated with BV for relapsed or refractory ALCL. The overall response rate to BV
      was 73% with complete response (CR) rate of 46%. The median failure-free survival
      and overall survival (OS) after BV were 15.5 month and not reached, respectively.
      The median duration of response was 27.6 months in patients who achieved CR by
      BV, while the median OS of those who did not achieve CR by BV was 9.5 months.
      There was no significant difference in OS between those who underwent stem cell
      transplant (SCT) and those who did not in patients who achieved CR after BV.
      However, if patients were in PR after BV, SCT was associated with significantly
      longer OS. Thirty patients experienced progressive disease on BV or required a
      subsequent treatment. The median OS after BV failure was 2.9 months with 2-year
      OS of 27.1%. There were seven long-term survivors (>=12 months) following
      failure. After an adequate response to subsequent salvage therapy, five patients
      underwent subsequent SCT (three allogeneic and two autologous), four of which
      were long-term survivors (17+, 25+, 32+, and 50+ months). In conclusion, BV
      failure is associated with a poor outcome in patients with ALCL, which defines a
      small but important group with unmet need. SCT may have benefit in patients with
      relapsed/refractory ALCL who failed BV.

PMID- 30209821
TI  - Theory of general balance applied to step wedge designs.
AB  - A standard idealized step-wedge design satisfies the requirements, in terms of
      the structure of the observation units, to be considered a balanced design and
      can be labeled as a criss-cross design (time crossed with cluster) with
      replication. As such, Nelder's theory of general balance can be used to decompose
      the analysis of variance into independent strata (grand mean, cluster, time,
      cluster:time, residuals). If time is considered as a fixed effect, then the
      treatment effect of interest is estimated solely within the cluster and
      time:cluster strata; the time effects are estimated solely within the time
      stratum. This separation leads directly to scalar, rather than matrix, algebraic
      manipulations to provide closed-form expressions for standard errors of the
      treatment effect estimate. We use the tools provided by the theory of general
      balance to obtain an expression for the standard error of the estimated treatment
      effect in a general case where the assumed covariance structure includes random
      effects at the time and time:cluster levels. This provides insights that are
      helpful for experimental design regarding the assumed correlation within clusters
      over time, sample size in terms of numbers of clusters and replication within
      cluster, and components of the standard error for estimated treatment effect.

PMID- 30209822
TI  - Perceptions of patient participation in symptom management: A qualitative study
      with cancer patients, doctors, and nurses.
AB  - AIM: To explore people with cancer, doctors', and nurses' understanding of and
      attitudes toward, patient participation in symptom management. BACKGROUND: In
      health service policies worldwide, patients are recognized as the important
      members of the treatment care team. The concept of patient participation can be
      understood from a variety of perspectives, reflecting the limited conceptual
      clarity and poor congruence between patients' and clinicians' understanding.
      DESIGN: A qualitative study conducted using individual interviews. METHODS: Forty
      one people with cancer, five doctors, and seven nurses were recruited from two
      oncological medical units of a cancer specialized hospital in Shanghai, China
      between November 2013 - March 2014. Individual interviews were semi-structured.
      Data were analysed through framework analysis. RESULTS: Patient participation was
      perceived as a mutual interaction requiring contribution from both patients and
      clinicians. Three main themes were uncovered: (a) information exchange is the key
      to patient participation; (b) negotiated decision-making can be achieved in
      various ways; and (c) patients' self-management can be a form of patient
      participation. Patient participation was recognized by both patients and
      clinicians as an important component of cancer care, however concerns relating to
      patients' limited knowledge and their ability to negotiate treatment decisions
      existed among most of the patients, doctors, and nurses. CONCLUSION: This study
      identified the wide range of activities where patient participation can occur in
      the context of cancer care. Positive recognition of patients' roles in treatment
      and care should be advocated among both patients and clinicians to facilitate
      patients' participation in their own care and enhance clinicians' skills in
      involving patients.

PMID- 30209823
TI  - Comment on ''Massive' metformin overdose' by Chiew et al.

PMID- 30209824
TI  - Evaluating classification performance of biomarkers in two-phase case-control
      studies.
AB  - Biomarkers are playing an increasingly important role in disease screening, early
      detection, and risk prediction. The two-phase case-control sampling study design
      is widely used for the evaluation of candidate biomarkers. The sampling
      probabilities for cases and controls in the second phase can often depend on
      other covariates (sampling strata). This biased sampling can lead to invalid
      inference on a biomarker's classification accuracy if not properly accounted for.
      In this paper, we adopt the idea of inverse probability weighting and develop
      inverse probability weighting-based estimators for various measures of a
      biomarker's classification performance, including the points on the receiver
      operating characteristics (ROCs) curve, the area under the ROC curve (area under
      the curve), and the partial area under the curve. In particular, we consider
      classification accuracy estimators using sampling weights estimated conditionally
      on sampling strata and further improve their efficiency through the use of
      estimated weights that additionally take into account the auxiliary variables
      available from the phase-one cohort. We develop asymptotic properties of the
      proposed estimators and provide analytical variance for making inference.
      Extensive simulation studies demonstrate excellent performance of the proposed
      weighted estimators, while the traditional empirical estimator can be severely
      biased. We also investigate the advantages in efficiency gain for estimating
      various classification accuracy estimators through the use of auxiliary variables
      in addition to sampling strata and apply the proposed method to examples from a
      renal artery stenosis study and a prostate cancer study.

PMID- 30209825
TI  - The personality profile of the accountable nurse and missed nursing care.
AB  - AIM: The aim of this study was to examine the mediating role of nurses' personal
      accountability in the relationships between nurse's personality and missed
      nursing care. BACKGROUND: Personal accountability is considered as a core value
      in nursing, shaped by the nurse's personality, education, socialization into the
      profession and experience. Personality antecedents may be uniquely suited to
      predicting accountability, since it reflects variation in individuals' deep
      seated values and beliefs. Personal accountability can be related to the
      prevalent phenomenon of missed nursing care (tasks that are omitted or delayed).
      DESIGN: A multicentre cross-sectional study with 290 nurses from direct-care
      nursing wards during 2017. Personality traits were assessed with the 44-item Big
      Five Inventory. Personal accountability was assessed with a 19-item scale. Missed
      nursing care was assessed with the 22-item MISSCARE survey. An indirect mediated
      path analysis was performed and compared with an alternative model with direct
      effects. RESULTS: Path-analyses findings supported a full-mediation model of
      accountability in the relationships between personality traits and missed nursing
      care. Conscientiousness, Agreeableness, Openness and Neuroticism, but not
      Extraversion, were significantly related to personal accountability. In addition,
      greater personal accountability was significantly related to lower frequency of
      missed nursing care. CONCLUSIONS: Personal traits are important antecedents of
      personal accountability, which relates to missed nursing care. Findings delineate
      the profile of the accountable nurse and might help in developing strategies for
      the selection of nurses with high personal accountability and determining the
      best means to strengthen accountable behaviours in the workplace.

PMID- 30209826
TI  - Factors influencing paternal involvement during infancy: A prospective
      longitudinal study.
AB  - AIMS: To explore factors influencing paternal involvement at 6 months postpartum
      and to detail the trend of these factors over a period of 6 months. BACKGROUND:
      There is a dearth of studies on paternal involvement during infancy in the unique
      Asian context. DESIGN: A prospective four-time point longitudinal design was
      adopted. METHODS: A total of 201 participants were recruited from a local
      hospital from May 2016 - December 2017 using convenience sampling. Self
      administered questionnaires were used for data collection. Data were
      statistically analysed. RESULTS: Parenting self-efficacy at 6-month postpartum,
      paternal involvement, and paternal postnatal depression on the day of wife's
      hospital discharge, wife in paid work and wife's antenatal class attendance
      significantly influenced paternal involvement at 6 months postpartum. A sub
      analysis of first-time and experienced fathers revealed that parenting self
      efficacy at 6-month postpartum, paternal involvement on the day of wife's
      hospital discharge and wife in paid work were significant factors influencing
      paternal involvement for first-time fathers. Significant factors influencing
      paternal involvement for experienced fathers were paternal involvement on the day
      of wife's hospital discharge and wife's antenatal class attendance. CONCLUSION:
      Fathers (first-time and experienced) who were involved during their infant's
      birth were also involved at 6-month postpartum. Healthcare professionals may
      encourage paternal involvement through teaching fathers infant care skills during
      the antenatal period, especially first-time fathers as they may be lacking in
      such skills, which may hinder their parenting satisfaction. Paternal involvement
      throughout the perinatal period can be enforced by healthcare professionals to
      promote paternal involvement.

PMID- 30209827
TI  - A longitudinal study of nurses' career choices: The importance of career
      expectations on employment in care of older people.
AB  - AIMS: To investigate how undergraduate nursing students' career expectations
      relate to their career choices, particularly employment in care of older people,
      in the first 10 years of nurses' careers. BACKGROUND: Due to an increasing demand
      for nurses, it is important to understand nurses' career choices over the course
      of their careers. DESIGN: A quantitative longitudinal study of 445 undergraduate
      nursing students based on a questionnaire survey and register data. METHODS: Data
      were analysed by multinomial logistic regression analyses. The questionnaire was
      distributed to all undergraduate nursing students in 2001-2003 in their final
      study semester at four universities in Norway (N = 445) to collect the students'
      career expectations. Register data on clinical fields for the first 10 years
      after graduation were merged into the survey in 2014 (Statistics Norway).
      RESULTS: With exception of the very first years after graduation, care of older
      people is the most common field for undergraduate nurses to enter for a career.
      This choice can be understood in light of nurses' career expectations. Among
      newly educated nurses, the choice to work in care of older people (rather than
      general hospital care) correlates with expectations of achieving a management
      position. Ten years after graduation, the likelihood of working in care of older
      people rather correlates with nurses' expectations of part-time work. CONCLUSION:
      The likelihood of moving into care of older people increases with time in nursing
      careers and relates to nurses' career expectations such as achieving a leadership
      position and working part-time.

PMID- 30209828
TI  - Iodo-Functionalized Salicylideneimine-Boron Complexes: Synthesis and
      Photosensitized Degradation of Organic Water Pollutants.
AB  - Boron-containing organic compounds are reported to have excellent luminescent
      properties, however, their ability to photosensitize singlet oxygen generation
      remains unexplored. The synthesis of several Schiff-base based boranils is
      reported, starting from commercially available salicylaldehydes and anilines. The
      iodo-functionalized derivatives were observed to aid in the photosensitized
      generation of singlet oxygen. Poly(methylmethacrylate) films incorporating these
      molecules were prepared and were demonstrated to be capable of serving as a
      reusable heterogeneous medium for the photosensitized degradation of organic
      water pollutants.

PMID- 30209829
TI  - Rhodium(III) Complex with a Bulky Cyclopentadienyl Ligand as a Catalyst for
      Regioselective Synthesis of Dihydroisoquinolones through C-H Activation of
      Arylhydroxamic Acids.
AB  - Catalytic reaction of arylhydroxamic acids with alkenes represents a convenient
      method for preparation of biologically active dihydroisoquinolones. Here, the
      rhodium(III) complex [(C5 H2 tBu2 CH2 tBu)RhCl2 ]2 , which allows one to carry
      out such reactions with high regioselectivity to obtain 4-substituted
      dihydroisoquinolones in 72-97 % yields, is described. The regioselectivity is
      provided by the bulky cyclopentadienyl ligand of the catalyst, which is formed
      through a [2+2+1] cyclotrimerization of tert-butylacetylene. The catalytic
      reaction tolerates various distant functional groups in alkenes, but is inhibited
      by bulky (e.g., tBu) or strongly coordinating (e.g., imidazolyl) substituents.
      Some of the prepared dihydroisoquinolones effectively inhibit growth of
      phytopathogenic fungi.

PMID- 30209830
TI  - Factors affecting withdrawal and donation attrition in the brains for dementia
      research cohort.
AB  - OBJECTIVES: To measure two forms of attrition in a cohort of volunteer brain
      donors: Withdrawal during life and non-donation at death. To test whether
      cognitive impairment independently predicts attrition. METHOD: Attrition rates
      were calculated for all registered participants and for all brain donors who had
      completed a baseline and follow-up assessment of cognition, health, and
      lifestyle. Attrition reasons were described, and attrition rates were compared by
      gender, age group, and cognitive status. Multivariate logistic regression was
      used to identify the factors which independently predicted during life and at
      death. RESULTS: A total of 3276 brain donors registered and 2307 (70.4%) remained
      in the cohort. Attrition rate overall was 5.9% for withdrawal and 13.8% for
      donation. Family disagreement and the brain bank not being informed of
      participant death were the most common reasons for withdrawal and donation
      attrition. Withdrawal was associated with having cognitive impairment (OR 2.0 95%
      CI 1.1-3.5), increased age (OR 3.1 95% CI 1.4-6.9), and lower education (OR 1.8
      95% CI 1.2-2.8). Participants exhibiting cognitive decline between assessments
      were more likely to withdraw (OR 4.9 95% CI 1.7-13.6). Participants living alone
      were almost twice as likely to die without donating (OR 1.9 95% CI 1.1-3.3).
      CONCLUSIONS: Attrition rates were relatively low, and consistent with other
      studies cognitive impairment, increased age, and less education predicted study
      withdrawal. Deaths of participants living alone were less likely to result in
      donation. Tailored, regular retention practices aimed at resolving family
      disagreement regarding donation decisions are required.

PMID- 30209831
TI  - Influence of anti-inflammatory diet and smoking on mortality and survival in men
      and women: two prospective cohort studies.
AB  - BACKGROUND: The associations between an anti-inflammatory diet and both all-cause
      and cause-specific mortality have been studied previously; however, the influence
      of an anti-inflammatory diet on survival time has not been investigated.
      Moreover, the potential modification of these associations by smoking status
      remains unclear. OBJECTIVE: The aims of this study were to examine the
      associations between an anti-inflammatory diet index (AIDI) and all-cause and
      cause-specific mortality, to determine the association between the AIDI and
      differences in survival time and to assess effect modification by smoking status.
      METHODS: The study population included 68 273 Swedish men and women (aged 45-83
      years) at baseline. The anti-inflammatory potential of the diet was estimated
      using the validated AIDI, which includes 11 potential anti-inflammatory and five
      potential pro-inflammatory foods. Cox proportional hazards and Laplace regression
      were used to estimate hazard ratios and differences in survival time. RESULTS:
      During 16 years of follow-up (1 057 959 person-years), 16 088 deaths [5980 due to
      cardiovascular disease (CVD) and 5252 due to cancer] were recorded. Participants
      in the highest versus lowest quartile of the AIDI had lower risks of all-cause
      (18% reduction, 95% CI: 14-22%), CVD (20%, 95% CI: 14-26%) and cancer (13%, 95%
      CI: 5-20%) mortality. The strongest inverse associations between the highest and
      lowest quartiles of AIDI and risk of mortality were observed in current smokers:
      31%, 36% and 22% lower risks of all-cause, CVD and cancer mortality,
      respectively. The difference in survival time between current smokers in the
      lowest AIDI quartile and never smokers in the highest quartile was 4.6 years.
      CONCLUSION: Adherence to a diet with high anti-inflammatory potential may reduce
      all-cause, CVD and cancer mortality and prolong survival time especially amongst
      smokers.

PMID- 30209832
TI  - Endovascular management of an aortic rupture following transcatheter aortic valve
      replacement.
AB  - We report a case of aortic rupture during transcatheter aortic valve replacement
      (TAVR) managed successfully by urgent stent-graft implantation.

PMID- 30209833
TI  - Transfusion knowledge of medical and surgical specialty board residents: a cohort
      study.
AB  - OBJECTIVES: This study was conducted to assess transfusion knowledge between
      different specialty board residents and to identify areas of need for further
      education. BACKGROUND: Physicians' knowledge of transfusion medicine (TM) is
      critical for patients' safety. Many clinicians who are involved in day-to-day
      transfusion practice have little or no formal training in TM. There are no
      studies to assess physician's TM knowledge locally. METHODS: A comprehensive
      anonymous survey was developed to assess baseline TM knowledge of all the
      residents. The survey is composed of different sections, including a
      questionnaire on resident's demographics, resident's self-reflection on their TM
      knowledge and 30 multiple choice questions addressing basic and clinical TM
      knowledge in two major domains: component selection and transfusion practice and
      transfusion safety and transfusion reactions. Finally, the residents' opinion on
      educational needs was assessed. RESULTS: A total of 130 residents were surveyed.
      The lowest score obtained among the two major domains assessed was in the
      transfusion safety and transfusion reaction domain, with a mean score of 4.34 of
      15 (SD +/- 3.27). The mean score obtained on component selection and transfusion
      practice was 7.1 of 15 (SD +/- 3.74). A substantial proportion of the residents
      (74.7%) admitted minimal baseline knowledge in the field of TM. Finally, 94.5% of
      the residents admitted the need for more education during residency, whereas
      49.5% thought additional education is required during the first year of practice.
      CONCLUSION: This survey shows serious TM knowledge deficiency and indicates the
      need for additional education among all physicians during training.

PMID- 30209834
TI  - Development of intervention-related quality indicators for renal clinical
      pharmacists using a modified Delphi approach.
AB  - OBJECTIVE: To develop a list of renal Quality Indicator Drug therapy problems (QI
      DTPs) that serve to advance renal pharmacy practice to improve patient care.
      METHODS: Eighteen (18) renal, clinical pharmacists participated in an internet
      based three-round modified Delphi survey. Each of the three rounds took
      approximately 2 weeks to complete. Panellists rated 30-candidate renal QI-DTPs
      using seven selection criteria and one overall consensus criterion on a nine
      point Likert scale. Consensus was reached if 75% or more of panellists assigned a
      score of 7-9 on the consensus criterion during the third Delphi round. KEY
      FINDINGS: All panellists completed three rounds of Delphi survey. Seventeen
      candidate renal QI-DTPs met the consensus definition. CONCLUSIONS: A Delphi panel
      of renal clinical pharmacists successfully identified 17 consensus renal QI-DTPs.
      Assessment and implementation of these QI-DTPs will serve to advance renal
      pharmacy practice and improve patient care.

PMID- 30209835
TI  - The relationship between hearing loss in older adults and depression over 12
      years: Findings from the Three-City prospective cohort study.
AB  - OBJECTIVE: The present study aims to examine the longitudinal relationship
      between hearing loss (HL) with depression in older adults over 12 years of follow
      up. METHOD: Eight thousand three hundred forty-four French community-dwelling
      adults aged 65 and above participated in the Three-City prospective population
      based study. Baseline relationships between self-reported mild and severe HL with
      depression-assessed by both the Mini International Neuropsychiatric Interview and
      by the Centre for Epidemiology Studies Depression scale-were explored using
      logistic regression analyses. Logistic mixed models assessed whether baseline HL
      was associated with incident depression diagnosis or symptom onset over 12 years
      in those who were depression-free at baseline. RESULTS: At baseline, mild and
      severe HL were associated with depression symptoms as assessed by the CESD (OR =
      1.29, 95% CIs 1.14-1.47; OR = 1.51, 95% CIs 1.22-1.87; respectively), although
      only mild HL was significantly related to major depression diagnosis (OR = 1.51,
      95% CIs 1.07-2.12). Over 12 years, mild and severe HL were associated with
      incident depression as assessed by the CESD in those without depression at
      baseline (OR = 1.36, 95% CIs 1.15-1.61; OR = 1.69, 95% CIs 1.15-2.30;
      respectively), but was not associated with a major depression diagnosis.
      CONCLUSIONS: Both mild and severe thresholds of HL are associated with depression
      symptoms over time, but not with incident diagnosis of major depression. Improved
      and ongoing detection of subthreshold depression amongst older adults with HL may
      improve quality of life for this population.

PMID- 30209836
TI  - Circulating plasma microRNAs as biomarkers for iron status in blood donors.
AB  - OBJECTIVES: To investigate whether microRNAs can serve as biomarkers for iron
      status in blood donors. BACKGROUND: Serum ferritin is a widely used biochemical
      test for detecting iron deficiency, but it has its limitations. Certain microRNAs
      (miRNAs) reportedly have a role in regulating iron homeostasis. Circulating
      miRNAs have been reported as potential biomarkers for various conditions but have
      not yet been studied in iron deficiency. METHODS: Participating blood donors were
      divided into two groups: high ferritin (HF) (>150 ug L-1 ) and low ferritin (LF)
      (<15 ug L-1 ). MiRNA analysis was performed by an miRNA profiling service
      (Exiqon) using commercial qPCR assays. The study had two phases: (i) a pilot
      study (20 participants) where 179 miRNAs were analysed and (ii) a confirmation
      study (50 participants) of 13 selected miRNAs. RESULTS: Mean serum ferritin was
      13.8 ug L-1 in the LF arm compared to 231 ug L-1 in the HF group (P < 0.001).
      Hepcidin plasma levels were higher in the HF arm (P < 0.001), whereas soluble
      transferrin receptor 1 was higher in the LF group (P < 0.001). In the pilot
      study, samples did not separate according to study group on unsupervised
      analysis. When directly comparing HF vs LF groups, 17 miRNAs were differentially
      expressed (P < 0.05, t-test) but did not pass correction for multiple testing.
      The confirmation study of 13 selected miRNAs verified these findings as no miRNA
      was significantly different between the study groups. CONCLUSION: In this study,
      circulating plasma miRNAs did not emerge as promising biomarkers for iron status
      in healthy individuals. However, in the future, alternative detection methods
      such as next-generation sequencing might indicate miRNAs that correlate with iron
      stores.

PMID- 30209837
TI  - Exfoliation of Graphene by Dendritic Water-Soluble Zinc Phthalocyanine
      Amphiphiles in Polar Media.
AB  - Two zinc phthalocyanines (ZnPcs) have been equipped with Newkome-type dendritic
      branches of increasing size and number of terminal carboxylate functional groups.
      The negatively charged carboxylates render these polyelectrolytes soluble in
      polar media such as methanol or buffered water. Sonication of the ZnPcs with
      graphene allowed for pronounced non-covalent binding of the ZnPc moieties on the
      graphene surface. These hybrid systems were fully characterized via UV/Vis, AFM,
      TEM, Raman and transient absorption spectroscopy, yielding insights into the
      electron donating nature of the novel phthalocyanine structures.

PMID- 30209838
TI  - Bacteria-Based Materials for Stem Cell Engineering.
AB  - Materials can be engineered to deliver specific biological cues that control stem
      cell growth and differentiation. However, current materials are still limited for
      stem cell engineering as stem cells are regulated by a complex biological milieu
      that requires spatiotemporal control. Here a new approach of using materials that
      incorporate designed bacteria as units that can be engineered to control human
      mesenchymal stem cells (hMSCs), in a highly dynamic-temporal manner, is
      presented. Engineered Lactococcus lactis spontaneously colonizes a variety of
      material surfaces (e.g., polymers, metals, and ceramics) and is able to maintain
      growth and induce differentiation of hMSCs in 2D/3D surfaces and hydrogels.
      Controlled, dynamic, expression of fibronectin fragments supports stem cell
      growth, whereas inducible-temporal regulation of secreted bone morphogenetic
      protein-2 drives osteogenesis in an on-demand manner. This approach enables stem
      cell technologies using material systems that host symbiotic interactions between
      eukaryotic and prokaryotic cells.

PMID- 30209839
TI  - The Worldwide Graphene Flake Production.
AB  - There are hundreds of companies worldwide claiming to produce "graphene," showing
      a large variation in its properties. A systematic and reliable protocol is
      developed to test graphene quality using electron microscopy, atomic force
      microscopy, Raman spectroscopy, elemental analysis, X-ray photoelectron
      spectrometry, and scanning and transmission electron microscopy, which is used to
      study graphene from 60 producers. The statistical nature of the liquid-phase
      exfoliation of graphite is established. It is shown that the current
      classification of graphene flakes used in the market is erroneous. A new
      classification is proposed in terms of distribution functions for number of
      layers and flake size. It is shown unequivocally that the quality of the graphene
      produced in the world today is rather poor, not optimal for most applications,
      and most companies are producing graphite microplatelets. This is possibly the
      main reason for the slow development of graphene applications, which usually
      require a customized solution in terms of graphene properties. It is argued that
      the creation of stringent standards for graphene characterization and production,
      taking into account both the physical properties, as well as the requirements
      from the particular application, is the only way forward to create a healthy and
      reliable worldwide graphene market.

PMID- 30209840
TI  - One size does not fit all-evolution of opioid agonist treatments in a
      naturalistic setting over 23 years.
AB  - BACKGROUND AND AIMS: Opioid agonist treatment (OAT) is currently the most
      effective treatment for people with opioid dependence. In most countries,
      however, access to the whole range of effective medications is restricted. This
      study aims to model the distribution of different OAT medications within a
      naturalistic and relatively unrestricted treatment setting (Zurich, Switzerland)
      over time, and to identify patient characteristics associated with each
      medication. METHODS: We used generalized estimating equation analysis with data
      from the OAT register of Zurich and the Swiss register for heroin-assisted
      treatment (HAT) to model and forecast the annual proportion of opioids applying
      exponential distributions until 2018 and patient characteristics between 1992 and
      2015. RESULTS: Data from 11 895 patients were included in the analysis. Methadone
      remains the mainstay of OAT, being prescribed to two-thirds of patients.
      Following its approval, the proportion of HAT increased rapidly and is now
      constant at 12.16% [95% confidence interval (CI) = 11.15-13.17]. The initial
      increase of proportions of buprenorphine or slow-release oral morphine (SROM)
      following their approval for OAT was slower. While in 2014 both medications had a
      proportion of 10.2% and 10.3%, respectively, our model predicts a further
      increase of SROM to 19.9% in 2018, with a ceiling level of 25.19% (21.40-28.98%)
      thereafter. SROM patients display characteristics similar to those treated with
      methadone; buprenorphine patients show the highest social integration; and HAT
      patients are the most homogeneous group, with highest mean age, most widespread
      injecting experience and lowest social integration. CONCLUSIONS: Based on data
      from Zurich, Switzerland from 1992 to 2015, there is no evidence for an excessive
      demand for a single medication in a naturalistic and liberal opioid agonist
      treatment setting. Rather, the specific patient characteristics associated with
      each medication underline the need for diversified treatment options for opioid
      dependence.

PMID- 30209842
TI  - Impact of Helicobacter pylori and/or Helicobacter pylori-related metabolic
      syndrome on gastroesophageal reflux disease- Barrett's esophagus- esophageal
      adenocarcinoma sequence.

PMID- 30209841
TI  - "Imagine if I'm not here, what they're going to do?"-Health-care access and
      culturally and linguistically diverse women in prison.
AB  - BACKGROUND: Women in prison have complex medical needs and poorer health status
      than the general population. Culturally and linguistically diverse (CALD) women
      in prison, particularly those with limited English proficiency (LEP), have
      distinct needs and risk additional isolation, discrimination and marginalization
      when they are in prison. OBJECTIVE: We sought to examine how cultural and
      linguistic diversity, particularly LEP, affects the health-care experiences of
      women in prison. DESIGN, SETTING AND PARTICIPANTS: We conducted focus groups and
      semi-structured qualitative interviews with CALD women and frontline nursing
      staff in the three female Correctional Centres in New South Wales, Australia.
      RESULTS: Participants comprised 30 women in prison and nine nurses. Both women
      and staff reported communication difficulties as a significant and additional
      barrier to accessing and receiving health care. For some women with LEP, barriers
      to care were perceived as discrimination. Fellow prisoners were often utilized as
      support persons and informal interpreters ("peer interpreters") in place of
      formally trained interpreters. While peer interpreters were perceived as useful,
      potential challenges to their use were vulnerability to coercion, loss of
      confidentiality, untrained health advice and errors of interpretation.
      CONCLUSION: The persistent use of peer interpreters in prison is complicated by
      the lack of clearly defined roles, which can include informal peer support roles
      and lay health advice. These are highly complex roles for which they are unlikely
      to be adequately trained or supported, despite perceived benefits to their use.
      Improved understanding and facilitation of health-related communication could
      enhance equity of access for CALD women in prison.

PMID- 30209843
TI  - Application of proton transfer reaction mass spectrometry for the assessment of
      toluene removal in a nonthermal plasma reactor.
AB  - Proton transfer reaction mass spectrometry (PTR-MS) is a mature technique for the
      real-time measurement and monitoring of volatile organic compounds in the
      atmosphere. In this paper, a modified quantification method for PTR-MS was used
      to assess the performance of nonthermal plasma (NTP) reactor for the removal of
      toluene which was widely used in industrial production processes. Toluene and 11
      corresponding organic by-products were tentatively identified and quantified by a
      proton transfer reaction time-of-flight mass spectrometer. The degradation
      dynamics of toluene and the formation of organic by-products were monitored in
      real-time (resolution = 1 second) under "plasma off" and "plasma on" conditions.
      We conclude that initial concentration and gas flow rate were the key parameters
      in the health risk assessment of NTP for the removal of toluene. The toluene
      removal efficiency and CO2 selectivity decreased with increasing upstream toluene
      concentration or gas flow rate, whereas the health risk influence index increased
      with increasing upstream toluene concentration or gas flow rate. The highest
      removal efficiency of toluene (100%), CO2 selectivity (53.2%), and the best
      health risk influence index for organic by-products (0.11) were achieved when the
      toluene concentration was kept at 105 ppmv and flow rate at 0.4 L/minute. The
      results demonstrate that PTR-MS is a promising tool to improve the practical
      applications of volatile organic compound removal by NTP because it can be used
      to optimize the NTP working conditions by providing a precise, fast, and clear
      health risk assessment for organic by-products based on their real-time analysis.

PMID- 30209844
TI  - Airline pilots with substance use disorders: to care for or to control?

PMID- 30209845
TI  - The Cone Evasion Walk test: Reliability and validity in acute stroke.
AB  - OBJECTIVE: To estimate the reliability and validity of the Cone Evasion Walk test
      (CEW), a new test assessing the ability to evade obstacles, in people with acute
      stroke. METHODS: To estimate the reliability of the CEW, video recordings of 20
      people with acute stroke performing the test were assessed by 10 physiotherapists
      on two occasions, resulting in a total of 400 ratings. Patients performed the CEW
      (n = 221), functional ambulation classification (FAC; n = 204), Timed Up and Go
      (TUG; n = 173), TUG cognitive (TUG-cog; n = 139), Serial 7s attention task from
      the Montreal Cognitive Assessment (MoCA-S7; n = 127), and the Star Cancellation
      Test (SCT; n = 151). These tests and side of lesion (n = 143) were used to
      examine construct validity. The predictive validity was evaluated in relation to
      falls during the following 6 months (n = 203). RESULTS: The intraclass
      correlation coefficients for intrarater and interrater reliability were 0.88
      0.98. For validity, there were significant correlations between the CEW and FAC
      (rs  = -0.67), TUG (rs  = 0.45), MoCA-S7 (rs  = -0.36), and SCT total score (rs 
      = -0.36). There was a significant correlation between the number of cones touched
      on the left side and the proportion of cancelled stars on the left (rs  = -0.23)
      and right (rs  = 0.23) side in the SCT. Among right hemisphere stroke
      participants (n = 79), significantly more persons hit cones on the left side (n =
      25) than the right side (n = 8), whereas among those with a left hemisphere
      stroke (n = 64) significantly more persons hit cones on the right side (n = 11)
      than the left (n = 3). Cox regression showed that participants who touched four
      to eight cones had an increased risk of falls over time (hazard ratio 2.11, 95%
      CI [1.07, 4.17]) compared with those who touched none. CONCLUSION: The new CEW
      test was reliable and valid in assessing the ability to evade obstacles while
      walking and to predict falls in patients with acute stroke.

PMID- 30209848
TI  - Letter from Vietnam.

PMID- 30209846
TI  - The role of skin testing and extended antibiotic courses in assessment of
      children with penicillin allergy: An Australian experience.
AB  - AIM: To determine if skin testing (ST) in addition to extended oral provocation
      challenge (OPC) is necessary for beta-lactam allergy verification in an
      Australian paediatric population. METHODS: This was a retrospective study (176
      children) that undertook assessments for beta-lactam allergy from 2006 to 2015 at
      a tertiary paediatric hospital. Patients either underwent direct OPC without ST
      or ST plus challenge if ST was negative. RESULTS: The analysis included children
      with a history of varying rash types/severity as well as angioedema and reported
      anaphylaxis. A direct OPC was undertaken in 73 children. Three children reacted
      with one anaphylaxis. A total of 103 children underwent ST, with 13 children
      (12.6%) reacting. Of the 90 who subsequently proceeded to OPC, 4 reacted. A total
      of 132 children were given an extended oral course of the culprit antibiotic, to
      which 6 children reacted. CONCLUSIONS: A direct OPC with the culprit drug in
      Australian children can be safely performed, avoiding resource-intensive and
      painful ST. Our data demonstrate that a prior history of anaphylaxis does not
      necessarily predict IgE-mediated allergy, as detected by positive immediate ST or
      reactions to oral challenge. Such history should not detract from efforts to
      assess these children for antibiotic allergy. We suggest that extended courses of
      at least 5 days are important in paediatric antibiotic de-labelling as six
      children (4.5% of those who were prescribed the extended course) reacted in our
      study and even developed symptoms late in the extended course, from days 2 to 6.

PMID- 30209847
TI  - Resilience in nurses in terms of perceived social support, job satisfaction and
      certain variables.
AB  - AIM: This study investigated the resilience of nurses, the factors that
      contribute to resilience, and its relationship with perceptions of social support
      and job satisfaction. BACKGROUND: Resilience plays an important role in how
      nurses cope with work-related stressors. METHODS: A descriptive study was
      conducted with 242 nurses working at three public hospitals in Turkey. Data were
      collected using a descriptive data form, the Resilience Scale for Adults (RSA),
      the Multidimensional Scale of Perceived Social Support (MSPSS) and the Minnesota
      Job Satisfaction Scale (MJSS). RESULTS: Nurses' mean scores on the RSA, MSPSS,
      and MJSS were 99.80 +/- 4.43, 66.66 +/- 13.30, and 3.31 +/- 0.72, respectively.
      Statistically significant relationships were detected between resilience and five
      factors: age, gender, mother's educational level, work experience and working
      hours (p < 0.05). A statistically significant positive correlation was also
      observed between MJSS score and both total RSA and family support subscale scores
      (p < 0.05). CONCLUSION: The resilience, perceived social support, and job
      satisfaction of participating nurses were moderate. Significant factors in their
      resilience were age, gender, mother's educational level, work experience, working
      hours, perceived social support and job satisfaction. IMPLICATIONS FOR NURSING
      MANAGEMENT: Nurse managers can use the results to plan interventions that improve
      resilience among nurses.

PMID- 30209849
TI  - MRI Profile and Collateral Status in Patients with a Transient Ischemic Attack
      and an Intracranial Artery Occlusion.
AB  - BACKGROUND AND PURPOSE: Transient ischemic attack may rarely reveal an
      intracranial artery occlusion. We analyzed acute magnetic resonance imaging (MRI)
      patterns and early outcome after reperfusion therapy in these cases. METHOD:
      Clinical and imaging data were taken retrospectively from our comprehensive
      stroke center registry. Two MRI patterns were determined. Pattern A: full
      mismatch with negative diffusion-weighted imaging (DWI) and perfusion defect.
      Pattern B: large mismatch with positive DWI and perfusion defect. MRI-derived
      collateral flow maps were automatically generated from the raw of dynamic
      susceptibility contrast MRI. Patients were treated either by recombinant tissue
      plasminogen activator (rtPA) alone or in combination with mechanical
      thrombectomy. RESULTS: From October 1, 2010 to May 15, 2016, 1,019 patients were
      admitted and treated by t-PA within 4.5 hours of stroke onset of them; 14 had a
      transient ischemic attack (TIA) within the 6 hours preceding MRI. Perfusion
      imaging was performed in 11 patients. An arterial occlusion was found in all of
      them, 11 patients had a distal anterior circulation occlusion, whereas 3 patients
      (21%) had a proximal occlusion. According to MRI, 6 patients showed pattern A,
      whereas 5 patients had pattern B. Good collaterals were observed in 10 patients
      (6 patients with grade 3 and 4 patients with grade 4), whereas 1 patient had poor
      collaterals (grade 2). The day 1 National Institutes of Health Stroke Scale
      median was 0. Modified Rankin Scale median at 3 months was 0. CONCLUSION: TIAs
      may reveal acute intracranial artery occlusion. Acute MRI may able to assist in
      therapeutic decision.

PMID- 30209850
TI  - Effects of Gadodiamide and Gadoteric Acid on Rat Kidneys: A Comparative Study.
AB  - BACKGROUND: Gadolinium-based contrast agents are complex chelates to provide
      contrast in NRI. However, recent studies have highlighted the deposition of free
      Gd+3 ion in various tissues. PURPOSE: To evaluate the histopathological and
      immunohistochemical changes on rat kidney tissue following both macrocyclic
      (gadoteric acid) and linear (gadodiamide) agents under the hypothesis that
      gadolinium-based contrast agents (GBCA) lead to toxic, free Gd+3 accumulation in
      tissues. STUDY TYPE: The local Animal Care Committee approved the prospective
      animal study. ANIMAL MODEL: Thirty-two healthy Sprague-Dawley male rats were
      administered 2 mmol/kg gadodiamide and gadoteric acid for the first 4 days for 5
      weeks. Group 1 received no drug (control, n = 8) and Group 2 (n = 8) was
      administered 0.1 ml/kg saline. Group 3 was administered 0.1 mmol/kg gadodiamide
      and Group 4 (n = 8) was administered 2 mmol/kg gadoteric acid. ASSESSMENT:
      Biochemical, histopathological, and immunohistochemical changes in testis kidney
      tissue were evaluated at the end of 10 weeks. STATISTICAL TESTS: Differences
      between groups were analyzed using the nonparametric Kruskal-Wallis test followed
      by one-way analysis of variance and the Tamhane test, also followed by Turkey's
      HSD test. RESULTS: Gadolinium increased serum urea, Ca+2 , and Caspase-3 positive
      tubular cell number. Larger Bowman capsules shrank proximal and distal tubules
      were revealed in the gadodiamide and gadoteric acid groups compared to the
      control group (P < 0.05). Histopathologic examination showed significantly more
      interstitial fibrosis, amyloid deposits, and vasocongestion in the gadodiamide
      group than the gadoteric acid and control groups, while the gadoteric acid group
      demonstrated significantly more leukocytic infiltration with atrophied proximal
      and distal tubules than the gadodiamide and control groups (P < 0.05). DATA
      CONCLUSION: GBCA administration causes significant histopathologic changes in
      kidney tissue. This study advocates additional investigation to assess the in
      vivo safety of GBCAs. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. MAGN.
      RESON. IMAGING 2018.

PMID- 30209851
TI  - Does muscle energy technique have an immediate benefit for women with pregnancy
      related pelvic girdle pain?
AB  - OBJECTIVE: Pregnancy-related pelvic girdle pain (PPGP) is a common and
      debilitating condition. Muscle energy techniques (METs) are used in the
      management of PPGP. This study aimed to determine the immediate effectiveness of
      a MET in the management of pain in women with PPGP within a single session of
      physiotherapy. METHODS: This study was a randomized, crossover, sham-controlled
      trial. Women (N = 80), M (SD), 30 (5) years of age and 29 (5) weeks of gestation
      with PPGP were included in the study. All participants were treated with a MET
      and sham transcutaneous electrical nerve stimulation in a randomized order,
      followed by standard physiotherapy during a single physiotherapy session. The
      primary outcome measures were the self-report of pain using a visual analogue
      scale and function using the Timed Up and Go. The secondary outcome was the
      duration of single leg stance (SLS). Clinical measures were taken prior to the
      first intervention and immediately following each of the interventions, a total
      of four times. RESULTS: There was no statistically significant difference between
      scores for the visual analogue scale, Timed Up and Go, or duration of SLS between
      participants following the use of a MET, sham transcutaneous electrical nerve
      stimulation, or standard care, which was recorded after each intervention (p >=
      0.72). There was a consistent and statistically significant (p value, mean
      difference) improvement in pain (p < 0.001, 2.6), function (p < 0.001, 1.0 s),
      and left SLS (p < 0.001, 4.4 s) and right SLS (p < 0.001, 4.7 s) from baseline
      compared with each time of measurement thereafter. CONCLUSIONS: The improvements
      measured may have been due to a placebo effect with the knowledge that care is
      being provided, mechanical unloading during the session, or familiarization with
      the test procedures. The mechanism(s) that led to improvements in pain and
      function remain unknown, however, does not preclude from women with PPGP being
      offered physiotherapy care.

PMID- 30209852
TI  - Introduction and uptake of electronic growth charts in southern New Zealand.
AB  - AIM: The introduction of an electronic system for recording and displaying growth
      measurements replaces multiple paper growth charts and theoretically improves the
      availability and consistency of information to support clinical decision-making.
      Introducing this in a single New Zealand District Health Board provided the
      opportunity to evaluate usage in hospital settings and determine the uptake of
      growth recording in a defined population. METHODS: All records between 2010 and
      2015 in the Southern District Health Board (SDHB) anthropometry database were
      downloaded and examined in a retrospective cohort analysis. Records were
      extracted after matching to demographic and clinical setting data from the
      hospital patient management system. RESULTS: Analysis included 30 670 data entry
      points, representing 8551 children. Data entry increased over time to a maximum
      of 8407 observations in 2015. By the fifth year of use, up to 67% of available
      clinical encounters had anthropometry recorded in the outpatient department.
      Rates were lower in the inpatient setting, where only up to 18.4% had
      anthropometry recorded. The errors identified were low (0.2% of all data). Weight
      was the most commonly recorded measurement (98.2% of anthropometry entries, 35.1%
      of available clinical presentations). Height was available for 82.6% of entries
      and 29.5% of presentations. A body mass index z-score was available for 81.5% of
      entries and 29.1% of presentations. A head circumference was available for 50.2%
      of children <2 years age who had anthropometry recorded. CONCLUSIONS: The
      introduction of an electronic anthropometry database has been successful with
      increasing rates of use over time, especially in outpatient clinics. Further
      focus to improve inpatient recording of height and weight is needed.

PMID- 30209853
TI  - Assessment of tricuspid valve by two- and three-dimensional echocardiography with
      special reference to percutaneous repair and prosthetic valve implantation
      procedures.
AB  - Moderate-to-severe tricuspid regurgitation affects approximately 1.6 million
      people in the United States. An estimated 8000 patients will undergo tricuspid
      surgery annually, leaving a large number of patients with this condition
      untreated. Many of these individuals who are not referred for surgery engender a
      large unmet clinical need; this may be primarily due to the surgical risk
      involved. In persons who are categorized as high-risk surgical candidates,
      percutaneous procedures present a viable alternative. The majority of
      developmental attention as regards percutaneous approaches has been focused on
      the aortic and mitral valves recently, but few data are available about the
      feasibility and efficacy of minimally invasive tricuspid valve treatment. We
      review the usefulness of two- and three-dimensional echocardiography in the
      assessment of the tricuspid valve with special reference to recent interest in
      percutaneous repair and prosthetic valve implantation procedures for severe
      functional tricuspid regurgitation.

PMID- 30209854
TI  - T2 Relaxometry and Diffusion Tensor Indices of the Hippocampus and Entorhinal
      Cortex Improve Sensitivity and Specificity of MRI to Detect Amnestic Mild
      Cognitive Impairment and Alzheimer's Disease Dementia.
AB  - BACKGROUND: Quantitative T2 and diffusion MRI indices inform about tissue state
      and microstructure, both of which may be affected by pathology before tissue
      atrophy. PURPOSE: To evaluate the capability of both volumetric and quantitative
      MRI (qMRI) of the hippocampus and entorhinal cortex (EC) for classification of
      amnestic mild cognitive impairment (aMCI) and Alzheimer's disease dementia (ADD).
      STUDY TYPE: Retrospective cross-sectional study. POPULATION: Consecutive cohorts
      of healthy age-matched controls (n = 62), aMCI patients (n = 25), and ADD
      patients (n = 14). FIELD STRENGTH/SEQUENCE: 3T using T1-weighted imaging, T2
      weighted imaging, T2 relaxometry and diffusion tensor imaging (DTI). ASSESSMENT:
      Montreal Cognitive Assessment and paired associate learning tests for cognitive
      state. Hippocampal subfield volumes by the automated segmentation of hippocampal
      subfields system from structural brain images. T2 relaxation time and DTI indices
      quantified for hippocampal subfields. The fraction of voxels with high T2 values
      (>20 ms above subfield median) was calculated and regionalized for hippocampus
      and EC. STATISTICAL TESTS: Support vector machine and receiver operating
      characteristic analyses from cognitive and MRI data. RESULTS: qMRI classified
      aMCI and ADD with excellent sensitivity (79.0% and 94.5%, respectively) and
      specificity (85.6% and 86.1%, respectively), superior to volumes alone (70.0% and
      84.5% for respective sensitivities; 82.2 and 91.1 for respective specificities)
      and similar to cognitive tests (61.7% and 87.5% for respective sensitivities;
      88.2% and 90.7% for respective specificities). Regions of high T2 are dispersed
      throughout each hippocampal subfield in aMCI and ADD with higher concentration
      than controls, and was most pronounced in the EC. No other individual qMRI marker
      than EC volume can separate aMCI from ADD, however. DATA CONCLUSION: qMRI markers
      of hippocampal and entorhinal tissue states are sensitive and specific
      classifiers of aMCI and ADD. They may serve as markers of a neurodegenerative
      state preceding volume loss. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 3 J.
      Magn. Reson. Imaging 2018.

PMID- 30209855
TI  - High-intensity inspiratory muscle training in bronchiectasis: A randomized
      controlled trial.
AB  - BACKGROUND AND OBJECTIVE: Inspiratory muscle training (IMT) enhances velocity of
      inspiratory muscle contraction and modifies inspiratory and expiratory time. This
      study aimed to examine the impact of high-intensity IMT (H-IMT) on exercise
      capacity in bronchiectasis. METHODS: Forty-five patients were included. Lung
      function, respiratory muscle strength and endurance, exercise capacity, dyspnoea,
      fatigue and quality of life (QOL) were evaluated. Patients were randomized into
      two groups: H-IMT and control groups. Twenty-three patients underwent H-IMT for 8
      weeks, using threshold loading with a target workload of maximal inspiratory
      pressure (MIP) of at least 70%, with 3-min cycles (as 2-min training: 1-min rest
      intervals) for 21 min. There was a total period of 14 min of loaded breathing and
      7 min of recovery. The control group (n = 22) underwent low-intensity IMT at 10%
      of the initial MIP and was maintained at the same intensity until the end of the
      training. RESULTS: After training, both MIP and maximal expiratory pressure (MEP)
      and the incremental shuttle walk distance were increased in the H-IMT group
      compared with the control group (P < 0.05). There was a significant difference in
      constant threshold load, time and pressure-time units in the H-IMT group (P <
      0.05) but not in the control group (P > 0.05). A significant decrease was found
      in fatigue in both groups (P < 0.05). The Leicester Cough Questionnaire social
      score for the H-IMT group decreased significantly after the treatment (P < 0.05).
      CONCLUSION: The H-IMT increased exercise capacity in patients with non-cystic
      fibrosis bronchiectasis. It has also positive effects on respiratory muscle
      strength and endurance, and social aspects of QOL.

PMID- 30209856
TI  - First case of secukinumab successful therapy in a very elderly psoriatic patient.

PMID- 30209857
TI  - Lobaplatin inhibits prostate cancer progression in part by impairing AR and ERG
      signal.

PMID- 30209859
TI  - Defects in interferon pathways as potential biomarkers of sensitivity to
      oncolytic viruses.
AB  - Increased sensitivity of cancer cells to viruses is a prerequisite for the
      success of oncolytic virotherapy. One of the major causes of such a phenotype is
      the disruption of innate antiviral defenses associated with dysfunction of type 1
      interferons (IFNs) that permits unlimited replication of viruses in cancer cells.
      Defects in IFN pathways help cancer progression by providing additional
      advantages to tumor cells. However, while these defects promote the survival and
      accelerated proliferation of malignant cells, they facilitate viral replication
      and thus enhance the efficiency of viral oncolysis. This review describes a broad
      spectrum of defects in genes that participate in IFN induction and IFN response
      pathways. Expression levels and/or functional activities of these genes are
      frequently low or absent in cancer cells, making them sensitive to virus
      infection. Therefore, certain specific defects in IFN signaling cascades might
      serve as potential biomarkers to help in identifying individual cancer patients
      who are likely to benefit from oncolytic virotherapy.

PMID- 30209860
TI  - Fifth Euro-Asian Congress of Dermatovenereologists, Riga, Latvia.

PMID- 30209861
TI  - Nurse managers' perceptions of care environment supporting older people's ability
      to function in nursing homes.
AB  - AIM: To describe nurse managers' perceptions of the care environment in nursing
      homes and how the residents' ability to function may be improved. BACKGROUND: The
      care environment, considered under physical, social and symbolic dimensions, can
      be used to maintain and enhance the residents' ability to function. METHODS: An
      exploratory, descriptive qualitative research design based on focus groups (n =
      4) was used. Fourteen nurse managers from six nursing homes in Southern Finland
      participated during 2014. Data were analysed using content analysis. RESULTS: The
      physical environment enables self-management, by facilitating a cosy, home-like
      and aesthetically pleasing environment and by the design of internal structures
      and assistive devices. The social environment was described as enabling by
      providing both private and communal spaces, encouraging personal privacy and self
      determination whilst supporting communal interaction and involvement. The
      symbolic environment was described as supporting a personal culture, care culture
      development and connecting the components of care perspectives in the community
      including nursing principles, recognizing and accepting variation in approaches
      to care. CONCLUSIONS: Development in the care environment requires more
      innovative approaches especially in the social and symbolic dimensions.
      IMPLICATIONS FOR NURSING MANAGEMENT: The results provide a framework for nurse
      managers for analysing and developing the care environment supporting residents'
      ability to function.

PMID- 30209858
TI  - Association of alcohol consumption with allergic disease and asthma: a multi
      centre Mendelian randomization analysis.
AB  - AIMS: To use the rs1229984 variant associated with alcohol consumption as an
      instrument for alcohol consumption to test the causality of the association of
      alcohol consumption with hay fever, asthma, allergic sensitization and serum
      total immunoglobulin (Ig)E. DESIGN: Observational and Mendelian randomization
      analyses using genetic variants as unbiased markers of exposure to estimate
      causal effects, subject to certain assumptions. SETTING: Europe. PARTICIPANTS: We
      included a total of 466 434 people aged 15-82 years from 17 population-based
      studies conducted from 1997 to 2015. MEASUREMENTS: The rs1229984 (ADH1B) was
      genotyped; alcohol consumption, hay fever and asthma were self-reported. Specific
      and total IgE were measured from serum samples. FINDINGS: Observational analyses
      showed that ever-drinking versus non-drinking, but not amount of alcohol intake,
      was positively associated with hay fever and inversely associated with asthma but
      not with allergic sensitization or serum total immunoglobulin (Ig)E. However,
      Mendelian randomization analyses did not suggest that the observational
      associations are causal. The causal odds ratio (OR) per genetically assessed unit
      of alcohol/week was an OR = 0.907 [95% confidence interval (CI) = 0.806, 1.019; P
      = 0.101] for hay fever, an OR = 0.897 (95% CI = 0.790, 1.019; P = 0.095) for
      asthma, an OR = 0.971 (95% CI =  0.804, 1.174; P = 0.763) for allergic
      sensitization and a 4.7% change (95% CI = -5.5%, 14.9%; P = 0.366) for total IgE.
      CONCLUSIONS: In observational analyses, ever-drinking versus not drinking was
      positively associated with hay fever and negatively associated with asthma.
      However, the Mendelian randomization results were not consistent with these
      associations being causal.

PMID- 30209862
TI  - Psychiatric adverse events in oseltamivir prophylaxis trials: Novel comparative
      analysis using data obtained from clinical study reports.
AB  - PURPOSE: Estimating the rate of adverse events (AEs) caused by a treatment in
      clinical trials typically involves comparing the proportions of patients
      experiencing AEs in intervention and control groups. However, potentially
      important information, including duration, recurrence, and intensity of events,
      is lost. In this study, we illustrate how the additional information can be
      obtained and incorporated into analyses of AEs. METHODS: Data on psychiatric AEs
      were extracted from clinical study reports (CSRs) provided by the manufacturer of
      oseltamivir in 4 prophylaxis randomised trials in adults and adolescents. We
      analysed the incidence, recurrence, duration, and intensity of events, using
      logistic regression models where the outcome compared was proportion of days
      suffering from an event, and developed novel presentation techniques. RESULTS:
      Psychiatric AEs were generally more frequent, longer, and more intense in the
      treatment than placebo arms. Logistic regression models confirm the apparent
      association overall (odds ratio [OR] 3.46, 95% confidence interval [CI] 1.28 to
      9.32), particularly for events classified as severe (OR 34.5, 95% CI 3.66 to
      325). However, the absolute difference in proportion of days suffering from
      severe psychiatric AEs between groups was small. CONCLUSIONS: This example
      analysis shows evidence of a causal effect of oseltamivir on psychiatric AEs, not
      apparent in the published versions of the same trials and a Cochrane review which
      showed a nonsignificant 81% increased odds of experiencing a psychiatric event.
      This unique and important finding was dependent on obtaining previously
      unavailable data from clinical study reports and using novel analyses and
      presentation methods.

PMID- 30209863
TI  - Chronic illness-related cognitive fusion explains the impact of body
      dissatisfaction and shame on depression symptoms in breast cancer patients.
AB  - Breast cancer is linked to psychological distress and mood disorders that are in
      turn associated with higher psychological dysfunction and decreased breast cancer
      survival. It is considered that psychological health in breast cancer is
      considerably affected by body image impairment, which in turn seems to be highly
      associated with shame. However, the impact of these variables on mental health
      may not be direct. The current study aimed to explore a comprehensive model
      regarding the role of chronic illness-related cognitive fusion in the
      relationship of body image dissatisfaction and chronic illness-related shame with
      depression symptoms. The sample was composed of 75 women with nonmetastatic
      breast cancer, recruited in a Radiotherapy Service in central Portugal. The
      conducted path model presented an excellent fit and accounted for 59% of the
      variance of depressive symptomatology. Further, it demonstrated that body image
      dissatisfaction's impact on depressed mood is significantly explained by the
      mechanisms of chronic illness-related shame and chronic illness-related cognitive
      fusion. It was also revealed that chronic illness-related cognitive fusion
      additionally mediated the impact of chronic illness-related shame on depression.
      These findings are suggestive of the importance of body image and chronic illness
      shame in the determination of breast cancer patients' depression symptoms and
      also the central role of chronic illness-related cognitive fusion in these
      relationships. Therefore, the implementation of acceptance and defusion-based
      psychotherapeutic interventions to improve mental health in cancer patients seems
      to be of great importance.

PMID- 30209864
TI  - Sun exposure among teenage and young adult cancer survivors in the United
      Kingdom.
AB  - Skin cancers are a common form of second malignant neoplasm among teenage and
      young adult cancer survivors (TYACS). The Children's Oncology Group specifies
      that TYACS should adhere to safe sun practices and be screened for skin cancer
      annually. Cross-sectional self-report data collected by our group indicate over a
      third of TYACS (n = 229; mean age: 19.8 years) intentionally sunbathe, with many
      reporting sunburn. TYACS sunbathing, sunburn, and sunbed use are similar to the
      general population (P > 0.05). These data suggest TYACS require intervention to
      limit sun exposure and improve their sun safety habits.

PMID- 30209865
TI  - Effect of intermediate disturbance on soil microbial functional diversity depends
      on the amount of effective resources.
AB  - Many anthropogenic environmental changes are leading to a rapid decline in soil
      microbial functional diversity. However, ecological mechanisms that can serve to
      counteract/resist the diversity loss remain largely underexplored. In particular,
      although intermediate disturbance and increased amount of effective resources can
      promote the diversity of higher organisms, the potential role of these factors,
      and their combination, in maintaining microbial functional diversity is poorly
      studied. We conducted a 5-year experiment in a Eurasian steppe, manipulating
      mowing, nitrogen addition, phosphorus addition and their combinations. Nitrogen
      addition decreased soil pH by ~0.6 and bacterial abundance by ~19.5%, causing a
      disturbance effect. Phosphorus addition significantly decreased the effective
      amount of soil carbon-, nitrogen-, phosphorus- and water-relevant resources.
      Across all nitrogen-addition treatments subject to intermediate disturbance,
      there was a significant positive correlation between soil effective resource
      amount and microbial gene richness (r > 0.6, p < 0.01), which was elevated, in
      part, due to the increased fungal abundance. In contrast, significant
      correlations between gene richness and resource amount were not found under low
      disturbance conditions. Overall, gene richness was greatest under conditions of
      both intermediate disturbance and ample effective resources, suggesting that the
      two factors could be manipulated in combination for the maintenance of microbial
      functional diversity.

PMID- 30209866
TI  - Constant abundances of ubiquitous uncultured protists in the open sea assessed by
      automated microscopy.
AB  - Protists have fundamental ecological roles in marine environments and their
      diversity is being increasingly explored, yet little is known about the
      quantitative importance of specific taxa in these ecosystems. Here we optimized a
      newly developed automated system of image acquisition and image analysis to
      enumerate minute uncultured cells of different sizes targeted by fluorescence in
      situ hybridization. The automated counting routine was highly reproducible, well
      correlated with manual counts, and was then applied on surface and deep
      chlorophyll maximum samples from the Malaspina 2010 circumnavigation. The three
      targeted uncultured taxa (MAST-4, MAST-7 and MAST-1C) were found in virtually all
      samples from several ocean basins (Atlantic, Indian and Pacific) in fairly
      constant cell abundances, following typical lognormal distributions. Their global
      abundances averaged 49, 23 and 7 cells ml-1 , respectively, and altogether the
      three groups accounted for about 10%-20% of heterotrophic picoeukaryotes. Our
      innovative high-throughput cell counting routine allows for the first time a
      direct assessment of the biogeographic distribution of small protists (< 5 MUm)
      and shows the ubiquity in sunlit oceans of three bacterivorous taxa, suggesting
      their key roles in marine ecosystems.

PMID- 30209867
TI  - Microbial metabolism of methanol and methylamine in the Gulf of Mexico: insight
      into marine carbon and nitrogen cycling.
AB  - One carbon (C1) metabolism plays an important role in marine carbon cycling but
      the dynamics and modes of C1 transformations are not fully understood. We made
      contemporaneous measurements of methylamine and methanol metabolism to elucidate
      the role of C1 compounds as sources of carbon, energy and nitrogen. Methanol and
      methylamine were predominantly used as an energy source in offshore waters
      (oxidation rate constant: kmethanol : 0.02-0.10 day-1 ; kmethylamine : 0.01-0.18
      day-1 ), but were also important sources of biomass carbon in coastal waters
      (assimilation rate constant: kmethanol : 0.04-0.10 day-1 ; kmethylamine : 0.01
      0.05 day-1 ). The relative extent of assimilation versus oxidation for these
      substrates correlated positively with chlorophyll, nutrients and heterotrophic
      bacterial production. Methanol oxidation and assimilation were stimulated
      significantly by nutrient addition. In contrast, methylamine metabolism was
      inhibited by ammonium or nitrate, suggesting that methylamine served as a
      nitrogen source. A preliminary metagenomic survey revealed a diverse population
      of putative C1-utilizing microorganisms. These results show that the
      remineralization of methylamine could provide both C and N sources for microbes.
      Both methanol and methylamine contribute to microbial energetic and carbon
      substrate demands with a distinctly different signature in nearshore versus
      offshore environments.

PMID- 30209868
TI  - A systematic review of risk factors for cataract in type 2 diabetes.
AB  - Type 2 diabetes (T2D) is a risk factor for cataract development. With T2D
      prevalence increasing, the burden of cataract-associated vision loss will also
      increase. We aimed to characterise cataract diabetes-specific risk factors to
      assist prevention and management strategies. As part of a systematic review, two
      investigators independently searched online electronic databases according to a
      predetermined protocol for relevant published data to end-March 2018. Studies
      were included if they were longitudinal with >=100 participants, diabetes was
      defined, a description of cataract assessment was provided, data were from
      humans, and the reports were in English. Study quality was assessed using the
      Newcastle Ottawa Scale and GRADE. Of 5255 publications identified, 19 from 13
      study populations were included. The overall risk of bias was low. There was
      between-study variability. Age and glycaemic control were consistently associated
      with cataract development in T2D, but blood pressure, diabetes duration, sex, and
      aspirin use were not. Serum lipids and smoking remain possible risk factors, but
      available data are inconclusive. Glycaemia is the only consistent modifiable risk
      factor amongst a range of candidate variables. Due to the lack of consistency of
      the available evidence, and since mortality associated with T2D is declining with
      the likelihood of increased cataract-associated vision loss, additional well
      conducted longitudinal studies are needed to identify modifiable risk factors
      that could prevent or delay cataract formation.

PMID- 30209869
TI  - beta-Aminoacrylate Synthetic Hydrogels: Easily Accessible and Operationally
      Simple Biomaterials Networks.
AB  - The development of new material platforms can improve our ability to study
      biological processes. Here, we developed a water-compatible variant of a click
      like polymerization between alkynoates and secondary amines to form beta
      aminoacrylate synthetic polyethylene glycol (PEG) based hydrogels. These
      materials are easy to access-PEG alkynoate was synthesized on a 100 gram scale
      and the amines were available commercially; these materials are also
      operationally simple to formulate-gel formation occurred upon simple mixing of
      precursor solutions without the need for initiators, catalysts, nor specialized
      equipment. Three-dimensional cell culture experiments also indicated
      cytocompatibility of these gels with >90 % viability retained in THP-1 and
      NIH/3T3 cells after 72 hours in culture. This hydrogel system therefore
      represents an alternative platform to other click and click-like hydrogels with
      improved accessibility and user-friendliness for biomaterials application.

PMID- 30209870
TI  - Management of Cardiovascular Disease Risk in Teens with Type 1 Diabetes:
      Perspectives of Teens With and Without Dyslipidemia and Parents.
AB  - Hypertension and dyslipidemia are often suboptimally managed in teens with type 1
      diabetes (T1D). Teen and parent perspectives on hypertension and dyslipidemia
      management need further study in order to enhance the development of CVD risk
      factor management plans. We sought to describe barriers to and strategies for CVD
      risk factor management. Teens with T1D with and without dyslipidemia and parents
      of teens with T1D with and without dyslipidemia underwent one-on-one semi
      structured interviews conducted by trained personnel at a diabetes center;
      interviews continued until thematic saturation was reached. Teens and parents of
      teens described their knowledge, attitudes, and beliefs regarding heart health
      and CVD risk factors (hypertension and dyslipidemia). Researchers undertook a
      content analysis and categorized central themes as strategies and barriers. In
      total, 22 teens and 25 parents completed interviews. Teens were 17.4+/-1.7 years
      old with T1D duration 9.7+/-4.0 years; 45% had dyslipidemia. Parents were between
      41-60 years old, 84% were mothers, and 40% had teens with dyslipidemia. Barriers
      to heart health included an obesity-promoting environment, parental distrust of
      medications, and limited teen knowledge about hypertension and dyslipidemia.
      Strategies included specific and realistic guidance from providers, family
      support of teen lifestyle management, and having exercise partners. While teen
      and parent perspectives were often similar, some themes applied only to teens or
      parents. Central themes provide actionable guidance to enhance hypertension and
      dyslipidemia management. Providers should consider teen and parent perspectives
      when managing CVD risk factors in order to enhance engagement with CVD risk
      management. This article is protected by copyright. All rights reserved.

PMID- 30209872
TI  - The interplay of EIIANtr with C-source regulation of the Pu promoter of
      Pseudomonas putida mt-2.
AB  - The presence of some sugars (e.g. glucose) downregulates the activity of the Pu
      promoter of plasmid pWW0 of Pseudomonas putida mt-2, which drives the upper TOL
      operon for biodegradation of m-xylene. Genetic evidence produced 20 years ago
      documented an effect of the EIIANtr (PtsN) protein of the nitrogen-related
      phosphoenolpyruvate-dependent phosphotransferase system (PTSNtr ) in such a C
      source control of Pu activity. In this study, we have exploited the wealth of
      recent information on the PTS of P. putida as well as transcriptomic data
      available in the last few years on this bacterium to revisit this question - and
      the role of EIIANtr as such. To this end, we examined Pu output under
      physiological conditions known to either phosphorylate PTS proteins to saturation
      or to deplete them altogether from high-energy phosphate. The results showed that
      Pu activity is checked by EIIANtr regardless of its phosphorylation state.
      However, such inhibition is intensified during growth on glucose (which
      correlates with more phosphate-free EIIANtr ) and partially relieved in fructose,
      which triggers phosphorylation of PTS proteins. These data explain former
      inconsistencies on the Pu-PTSNtr interplay and provides a better understanding of
      the metabolic and regulatory retroactivity between the TOL plasmid and its host
      metabolism.

PMID- 30209873
TI  - Investigation of surface structure and biocompatibility of chitosan-coated
      zirconia and alumina dental abutments.
AB  - BACKGROUND: For long-term success of dental implants, it is essential to maintain
      the health of the surrounding soft tissue barrier, which protects the bone
      implant interface from the microorganisms. Although implants based on titanium
      and its alloys still dominate the dental implant market, alumina (Al2 O3 ) and
      zirconia (ZrO2 ) implant systems are widely used in the area. However, they
      provide smooth and bioinert surfaces in the transmucosal region, which poorly
      integrate with the surrounding tissues. OBJECTIVE: The main aim of this research
      was to investigate the surface characteristics and biocompatibility of chitosan
      coated alumina and zirconia surfaces. MATERIALS AND METHODS: The substrates were
      coated via solution casting technique. Additionally, an aging process with a
      thermocycle apparatus was applied on the coated materials to mimic the oral
      environment. To define the morphology and chemical composition of the surfaces of
      untreated, chitosan-coated, and chitosan-coated-aged samples, scanning electron
      microscopy and energy dispersive X-ray spectrometry were used. The phases and
      bonds characterized by Fourier transform infrared spectroscopy and X-ray
      diffraction analysis. The human gingival fibroblast cells were used to evaluate
      cytocompatibility by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium salt
      assay. RESULTS: It was observed that both substrates were successfully coated
      with chitosan and the aging process did not significantly affect the integrity of
      the coating. The attachment and proliferation of human gingival fibroblast cells
      were shown to be good on both kinds of chitosan-coated surfaces. CONCLUSION:
      Coating zirconia and alumina surfaces with chitosan is an efficient surface
      modification for increasing biocompatibility and bioactivity of these materials
      in vitro.

PMID- 30209874
TI  - Role of social normative beliefs as a moderating factor in smoking intention
      among adolescent girls in Korea.
AB  - In this study, we investigated the relationship between risk-taking tendency and
      smoking intention as moderated by social normative beliefs among Korean female
      adolescents. A cross-sectional study was conducted with 274 female adolescents in
      middle school. Multiple regression and simple slope analyses were employed to
      test the moderating effects of social normative beliefs regarding smoking on the
      relationship between risk-taking tendency and smoking intention. Results
      determined that risk-taking tendency, social normative beliefs regarding smoking,
      and their interaction were significant factors influencing smoking intention
      among adolescents. Risk-taking tendency was associated with greater smoking
      intention among adolescents, with higher than average social normative beliefs
      regarding smoking. However, risk-taking tendency was not significantly associated
      with smoking intention for adolescents with lower than average social normative
      beliefs regarding smoking. In conclusion, social normative beliefs regarding
      smoking moderated the relationship between risk-taking intention and smoking
      intention among Korean female adolescents. Unique sociocultural perceptions about
      smoking behaviors of adolescents need to be reflected in smoking-prevention and 
      cessation programs.

PMID- 30209875
TI  - Clinical peri-implant parameters and inflammatory cytokine profile among smokers
      of cigarette, e-cigarette, and waterpipe.
AB  - BACKGROUND: To date, there has been no study identified that assessed peri
      implant parameters and local levels of proinflammatory cytokines between
      waterpipe smokers (WS) and electronic cigarette users (VS). To evaluate the true
      effect of the risk indicator (WS and VS), a positive control (cigarette smokers
      [CS]) was added in the study design. PURPOSE: To compare clinical and
      radiographic peri-implant parameters and proinflammatory cytokine profile in the
      peri-implant sulcular fluid (PISF) among CS, WS, VS, and nonsmokers (NS).
      MATERIALS AND METHODS: Forty CS, WS, VS, and NS were included. Details regarding
      demographics, duration of implants, and habits were recorded. Clinical
      examination for periodontal and peri-implant plaque index (PI), bleeding on
      probing (BOP), and probing depth (PD >= 4 mm) were assessed. Radiographic bone
      loss (RBL) was assessed using digital periapical radiographs and viewed on a
      calibrated computer screen using an image analyzer. Levels of tumor necrosis
      factor-alpha (TNF-alpha), interleukin (IL)-6, and IL-1beta in PISF were evaluated
      using enzyme-linked immunosorbent assay. RESULTS: Mean peri-implant PI (P < .05),
      PD >= 4 mm (P < .05), and total RBL (P < .01) was significantly higher among CS,
      WS, and VS compared with NS. Statistical differences in BOP were observed in NS
      (P < .01) compared to CS, WS, and VS. CS and WS showed significantly higher PD >=
      4 mm and RBL compared with VS (P < .05). Levels of TNF-alpha, IL-6, and IL-1beta
      were significantly higher in CS, WS, and VS compared to NS. There were no
      statistical differences in the mean levels of all proinflammatory cytokines among
      individuals in CS and WS. CONCLUSION: Tobacco smoking is associated with poor
      peri-implant health. The effect of waterpipe smoking was of largely the same
      extent as that of cigarette smoking. Higher levels of inflammatory cytokines in
      tobacco smokers may propose increased peri-implant inflammatory process which
      could play a principal role in the progression of peri-implant tissue damage.

PMID- 30209876
TI  - The Influence of Distant Substrates on the Outcome of Contact Electrification.
AB  - The magnitudes of the charges developed on contact-electrified polymers depend on
      not only the properties of these materials but also the nature of distant
      substrates on which the polymers are supported. In particular, image charges
      induced in conductive substrates can decrease charges on the polymers by arc
      discharge through the surrounding gas. This mode of charge dissipation occurs on
      timescales of milliseconds and can be prevented by insulating the sharp edges of
      the conductive supports.

PMID- 30209877
TI  - Oak extractive-induced stress reveals the involvement of new enzymes in the early
      detoxification response of Phanerochaete chrysosporium.
AB  - Extensive evidence showed that the efficiency of fungal wood degradation is
      closely dependent on their ability to cope with the myriad of putative toxic
      compounds called extractives released during this process. By analysing global
      gene expression of Phanerochaete chrysosporium after short oak extractive
      treatment (1, 3 and 6 h), we show that the early molecular response of the fungus
      concerns first mitochondrial stress rescue followed by the oxidation and finally
      conjugation of the compounds. During these early responses, the lignolytic
      degradative system is not induced, rather some small secreted proteins could play
      an important role in cell protection or signaling. By focusing on the functional
      characterization of an hitherto uncharacterized glutathione transferase, we show
      that this enzyme interacts with wood molecules suggesting that it could be
      involved in the detoxification of some of them, or act as a scavenger to prevent
      their cytosolic toxicity and favour their transport.

PMID- 30209878
TI  - The impact of a standardized inter-department handover on nurses' perceptions and
      performance in Republic of Korea.
AB  - AIMS: To evaluate the impact of a standardized inter-department nursing handover
      protocol from intensive care units to general wards on the nurses' perceptions
      and performance. METHODS: We developed an inter-department nursing handover
      protocol based on the situation, background, assessment and recommendation
      technique. All participating paediatric nurses were trained in this new protocol,
      which was then implemented for nine months in eight units of a children's
      hospital in the Republic of Korea. Data were extracted from a questionnaire and
      handover auditing using audio recording. RESULTS: Following the protocol's
      introduction, nurses' perceptions of handover effectiveness significantly
      improved (F = 5.17, p = .007), while their experience of handover errors
      significantly decreased (F = 12.85, p < .001). Furthermore, the prevalence of
      additive calls per handover decreased from 70.7% to 45.9% (chi2  = 9.88, p =
      .002), and the prevalence of handover-related errors decreased from 51.2% to
      32.4% (chi2  = 5.63, p = .023). Handover accuracy significantly increased (t = 
      5.12, p < .001) without prolonging the handover duration. CONCLUSIONS: The
      handover protocol positively influenced the nurses' perception of handover and
      clinical performance. IMPLICATIONS FOR NURSING MANAGEMENT: A standardized inter
      department handover helped intensive care unit nurses to improve their
      organisation and to provide ward nurses with sufficient information during
      handover, which could ensure safer transitions from intensive care units to
      wards.

PMID- 30209879
TI  - Added sugar and sodium levels in New Zealand processed fruit and vegetable-based
      products.
AB  - AIM: Fruit and vegetables are strongly promoted because of the nutrients they
      provide; many processed products contain added sugar and sodium. The present
      study aims to quantify the sugar and sodium content of pre-packaged fruit and
      vegetable-based products that are available in New Zealand supermarkets. METHODS:
      Nutrition Information Panel data were collected from non-frozen, processed fruit
      and vegetable products in New Zealand supermarkets (including soups, sauces, jams
      and spreads, pickles, chutneys and dips, and canned/bottled fruit and vegetables)
      where fruit and/or vegetables were the majority ingredient(s). RESULTS: With the
      exception of canned/bottled vegetables, more than 60% of products contained added
      sugar. Per serve, the median sugar content was highest in canned/bottled fruit
      (17.8 g). More than 75% of soups, vegetable-based sauces, pickles/chutneys and
      canned/bottled vegetables contained added sodium, with soups (722 mg) recording
      the highest median values per serve. CONCLUSIONS: Consumers need to be aware that
      although they are encouraged to eat a diet high in fruit and vegetables, there
      may be large quantities of added sugar and sodium in manufactured fruit and
      vegetable products that can have significant negative impacts on their health.
      Government health promotion campaigns encouraging the consumption of fruit and
      vegetables should be careful to target fresh, frozen and home-prepared foods, and
      work on educating the public about the lower nutritional quality associated with
      most processed fruit and vegetable products.

PMID- 30209880
TI  - Determinants of nurse absenteeism and intent to leave: An international study.
AB  - AIM: To determine factors associated with nurses' intent to leave their positions
      and absenteeism. BACKGROUND: There is a recognized global shortage of nurses but
      limited data describing and determining factors associated with nurse absenteeism
      and intent to leave. METHODS: This study involved a secondary analysis of the
      results from direct-care registered nurses' responses to the MISSCARE Survey,
      with data from seven countries included. Multi-level modelling was used to
      determine nurse characteristics and working environment factors associated with
      nurse absenteeism and intent to leave. RESULTS: The level of absenteeism and
      intent to leave varied significantly across countries, with registered nurses in
      Lebanon reporting the highest intention to leave within 12 months (43%) and
      registered nurses in Iceland and Australia the highest level of absenteeism (74%
      and 73%, respectively). Factors associated with outcomes included perceived
      staffing adequacy of unit, job satisfaction, and age of the nurse. CONCLUSIONS: A
      significant difference between countries was identified in nurse absenteeism and
      intent to leave. Increased perception of unit staffing inadequacy, lower job
      satisfaction, less nurse experience, and younger age were significant
      contributors to nurse absenteeism and intent to leave. IMPLICATIONS FOR NURSING
      MANAGEMENT: These findings suggest that regardless of country and hospital, by
      ensuring that units are adequately staffed and increasing job satisfaction,
      younger, less experienced nurses can be retained and absenteeism reduced.

PMID- 30209882
TI  - Vertical Assembly of Giant Double- and Triple-Decker Spoked Wheel Supramolecular
      Structures.
AB  - The double- or triple-decker 3D metallo-hexagons were obtained by self-assembly
      of multitopic tris-terpyridines with Cd2+ ions in near-quantitative yield.
      Comprising up to 72 ionic pairs, the multiple spoked wheels display
      characteristic reversible gelation properties under thermodynamic conditions. The
      supramolecular metallo-nanoarchitectures were characterized by 1 H NMR, 2D NMR
      (COSY and NOESY), and diffusion-ordered spectroscopy (DOSY) and HR-ESI-MS,
      traveling-wave ion mobility mass spectrometry (TWIM-MS), TEM, and AFM. For the
      first time, the self-assembly of 45 units at once was demonstrated to yield
      exceptional giant triple-decker hexagons of up to circa 42 000 Da.

PMID- 30209881
TI  - Incidence and risk of celiac disease after type 1 diabetes: A population-based
      cohort study using the health improvement network database.
AB  - OBJECTIVE: To determine the incidence of and risk factors for development of
      celiac disease (CD) in individuals with type 1 diabetes. METHODS: Cohort study
      using The Health Improvement Network (THIN), a UK primary care database of >13
      million people. Individuals with incident type 1 diabetes diagnosed at 1 to 35
      years of age between 1995 and 2015 with no previous diagnosis of CD were
      included. Cox regression was used to identify risk factors for CD, including age
      at diabetes diagnosis and sex, while adjusting for year of diagnosis to control
      for potential rising incidence in CD over time. RESULTS: Subjects (n = 9180; 43%
      female) had a median observation time of 5.1 years (interquartile range 2.0
      10.1). CD was diagnosed in 196 (2%) during follow up. Median time to diagnosis
      was 2.1 years, but 25% were diagnosed more than 5 years after diabetes diagnosis.
      Incidence (per 10 000 person-years) was greater in females (43.0 [95% confidence
      interval [CI] 35.2-52.0]) vs males (26.8 [95% CI 21.5-32.9]). In multivariable
      Cox regression stratified by childhood- vs young adult-onset diabetes, younger
      age at diabetes diagnosis within childhood (hazard ratio [HR] 0.91 [95% CI 0.88
      0.94]) and female sex among the adult-onset diabetes group (HR 3.19 [95% CI 1.39
      7.34]) were associated with greater risk of CD. CONCLUSIONS: As expected,
      incidence of CD was higher in individuals with childhood-onset diabetes vs those
      with adult-onset diabetes. However, individuals with diabetes are at risk of
      developing CD throughout childhood and adulthood, and prolonged screening after
      diagnosis may be warranted. Prospective studies are needed in order to guide risk
      stratified approaches to screening.

PMID- 30209883
TI  - Emergence of soil bacterial ecotypes along a climate gradient.
AB  - The high diversity of soil bacteria is attributed to the spatial complexity of
      soil systems, where habitat heterogeneity promotes niche partitioning among
      bacterial taxa. This premise remains challenging to test, however, as it requires
      quantifying the traits of closely related soil bacteria and relating these traits
      to bacterial abundances and geographic distributions. Here, we sought to
      investigate whether the widespread soil taxon Curtobacterium consists of multiple
      coexisting ecotypes with differential geographic distributions. We isolated
      Curtobacterium strains from six sites along a climate gradient and assayed four
      functional traits that may contribute to niche partitioning in leaf litter, the
      top layer of soil. Our results revealed that cultured isolates separated into
      fine-scale genetic clusters that reflected distinct suites of phenotypic traits,
      denoting the existence of multiple ecotypes. We then quantified the distribution
      of Curtobacterium by analysing metagenomic data collected across the gradient
      over 18 months. Six abundant ecotypes were observed with differential abundances
      along the gradient, suggesting fine-scale niche partitioning. However, we could
      not clearly explain observed geographic distributions of ecotypes by relating
      their traits to environmental variables. Thus, while we can resolve soil
      bacterial ecotypes, the traits delineating their distinct niches in the
      environment remain unclear.

PMID- 30209884
TI  - Low pre-treatment nutritional index is significantly related to poor outcomes in
      small cell lung cancer.
AB  - BACKGROUND: The importance of nutritional status and chronic inflammation has
      been emphasized in cancer. We investigated the impact of Onodera's prognostic
      nutritional index (OPNI) on clinical outcomes in small cell lung cancer (SCLC)
      patients. METHODS: Data from 220 SCLC patients treated with first-line platinum
      based chemotherapy from 2006 to 2017 were retrospectively reviewed. The OPNI was
      calculated as 10 * serum albumin level (g/dL) + 0.005 * absolute lymphocyte count
      (/mm3 ). Patients with an OPNI of > 45, 40-45, or < 40 were categorized in high,
      intermediate, or low OPNI groups, respectively. RESULTS: The proportion of non
      responders to first-line therapy increased as the OPNI decreased (high,
      intermediate, low OPNI groups: 6.7%, 18.0%, and 30.8%, respectively; P < 0.001).
      Early discontinuation of first-line therapy because of treatment toxicity
      occurred more frequently in the lower OPNI groups (high, intermediate, low OPNI
      groups: 5.8%, 21.3%, and 25.6%, respectively; P < 0.001). The one-year
      progression-free and overall survival rates in the high, intermediate, and low
      OPNI groups were 29%, 19%, and 3%, and 61%, 46%, and 23%, respectively. In
      multivariate analyses, the low OPNI group was independently associated with poor
      progression-free (hazard ratio 1.592; 95% confidence interval 1.009-2.511; P =
      0.046) and overall (hazard ratio 1.911; 95% confidence interval 1.208-3.024; P =
      0.006) survival compared to the high OPNI group. CONCLUSION: SCLC patients with
      an OPNI < 40 showed a low tolerance to chemotherapy and a poor prognosis. Further
      evaluation is needed to validate these findings.

PMID- 30209885
TI  - Comparable immunoreactivity rates of PD-L1 in archival and recent specimens from
      non-small cell lung cancer.
AB  - BACKGROUND: Molecular targeted therapy including the use of monoclonal antibodies
      directed against the immune checkpoints PD-L1 and PD-1 receptor have remarkably
      improved the therapeutic response and survival of cancer patients. The tumor
      expression level of PD-L1 can predict the response rate to checkpoint inhibitors.
      We evaluated whether the time interval between tumor tissue
      sampling/paraffinization and immunohistochemistry affects the staining level of
      PD-L1 in non-small cell lung cancer (NSCLC). METHODS: This study comprised 137
      patients with NSCLC. Tumors were stained with 22C3 or 28-8 antibodies. RESULTS:
      There was a significant correlation between the immunoreactivity rate of tumor
      tissues obtained using 22C3 and 28-8 clones. No statistical difference in
      immunoreactivity between archival and recent samples stained either with 22C3 or
      28-8 antibodies was observed. The immunoreactivity rate achieved with 22C3 or 28
      8 antibodies significantly correlated with tumor histological type and size, but
      not with specimen storage time, age, gender, smoking history, clinical stage, or
      lymph node metastasis. CONCLUSION: In brief, the results of this study show that
      the time interval between tissue sampling/paraffinization and immunohistochemical
      analysis has no influence on the immunoreactivity rate of PD-L1 in NSCLC.

PMID- 30209887
TI  - Lanthanide-Catalyzed Tandem Insertion of Secondary Amines with 2
      Alkynylbenzonitriles: Synthesis of Aminoisoindoles.
AB  - A lanthanide-catalyzed intermolecular hydroamination of 2-alkynylbenzonitriles
      with secondary amines has been disclosed, providing a streamlined access to a
      range of aminoisoindoles in moderate to excellent yields. The salient features of
      this reaction include high bond-formation efficiency, mild reaction conditions,
      100 % atomic efficiency and good functional group tolerance. This methodology has
      also been successfully applied to the construction of other nitrogen-containing
      compounds, such as 5 H-imidazo[2,1-a]isoindoles and isoquinolines. A plausible
      mechanism for the formation of aminoisoindoles involving initial N-H activation
      by a lanthanide complex followed by C=N insertion into a Ln-N bond to form an
      amidinate lanthanide intermediate, which undergoes the cyclization is proposed.

PMID- 30209886
TI  - Selective Anion Recognition by a Dynamic Quadruple Helicate.
AB  - An M2 L4 quadruple helicate, formed by wrapping four molecules of 1,4-bis(3
      pyridyloxy)benzene (L1 ) about two palladium(II) centers, is shown to bind anions
      within its internal cavity. 1 H NMR exchange experiments provide a quantitative
      measure of anion selectivity and reveal a preference for ClO4- over the other
      tetrahedral anions BF4- and ReO4- and the octahedral anion PF6- . X-ray crystal
      structures of [Pd2 (L1 )4 ]4+ helicates containing ClO4 , BF4- and I- reveal that
      the cavity size can dynamically change in response to the size of the guest.

PMID- 30209888
TI  - Nanotubes of NiCo2 S4 /Co9 S8 Heterostructure: Efficient Hydrogen Evolution
      Catalyst in Alkaline Medium.
AB  - The most important issue in water splitting is the development of efficient,
      abundant, and cost-effective hydrogen and oxygen evolution catalysts. The
      development of an efficient electrocatalyst for the hydrogen evolution reaction
      (HER) under alkaline conditions is described here following a simple hydrothermal
      route. Here, a method for the synthesis of NiCo2 S4 /Co9 S8 , Co9 S8 , and NiCo2
      S4 nanotubes has been developed. The NiCo2 S4 /Co9 S8 heterostructure has been
      introduced as an efficient electrocatalyst towards HER under alkaline conditions
      (1.0 m KOH). The vertically aligned nanotube heterostructure (NiCo2 S4 /Co9 S8 )
      shows the most efficient activity as compared to bare Co9 S8 and NiCo2 S4
      nanotubes. The heterostructure of NiCo2 S4 and Co9 S8 shows a significant anodic
      shift in the onset potential compared to the bare counterpart. NiCo2 S4 /Co9 S8
      can generate a current density of 10 mA cm-2 upon application of only -0.172 V
      vs. RHE, whereas Co9 S8 and NiCo2 S4 require -0.293 V and -0.239 V vs. RHE,
      respectively. The heterostructure formation and the nanotube morphology of Co9 S8
      and NiCo2 S4 facilitates a fast charge transportation which results in higher
      electrocatalytic activity. The hydrogen gas evolution rate of the NiCo2 S4 /Co9
      S8 heterostructure was determined to be 2.29 MUmol min-1 .

PMID- 30209889
TI  - Clinical Effects of Polymyxin B Hemoperfusion in Patients With Septic Shock
      Caused by Urinary Tract Infection.
AB  - Direct hemoperfusion with polymyxin B-immobilized fiber (PMX-DHP) has been widely
      used for severe sepsis and septic shock. However, data are limited regarding the
      clinical experience and efficacy of PMX-DHP for septic shock resulting from
      urinary tract infection (UTI). At our institution, 15 patients with septic shock
      resulting from a UTI received PMX-DHP from January 2013 to July 2017. The cause
      of the urosepsis was mainly obstructive pyelonephritis secondary to
      ureterolithiasis or neurogenic bladder. Average Acute Physiology and Chronic
      Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA)
      scores were 25.9 +/- 4.3 and 10.5 +/- 2.2, respectively. If patients were still
      hypotensive after initial resuscitation, we began PMX-DHP. Mean arterial pressure
      increased significantly from 58.3 +/- 9.6 mm Hg to 93.6 +/- 14.8 mm Hg just after
      PMX-DHP and to 94.7 +/- 16.9 mm Hg (P < 0.0001) 24 h after the treatment.
      Catecholamine index decreased significantly from 20.7 +/- 11.3 to 9.3 +/- 13.5 (P
      = 0.0001) 24 h after the treatment. Of 15 patients, 14 (93.3%) had survived 28
      days after admission. Our results suggest a possible role for PMX-DHP in the
      rapid stabilization of hemodynamics in patients with septic shock with an
      underlying UTI. These patients may be good candidates for PMX-DHP.

PMID- 30209890
TI  - Recruitment outcomes, challenges and lessons learned: the Healthy Communities
      Study.
AB  - BACKGROUND: The Healthy Communities Study (HCS) was a national study of community
      programs and policies that aimed to address childhood obesity; it necessitated
      recruitment of a large sample of children from communities throughout the United
      States. OBJECTIVE: The HCS aimed to complete visits with an average of 45
      children and 12 key informants from at least 120 communities, diverse with
      respect to region of the country, urbanicity, socioeconomic status, race,
      ethnicity and intensity of community programs and policies that aim to address
      childhood obesity. METHODS: Purchased address lists were utilized to select
      households for recruitment during Wave 1 of the study, and recruitment of
      families through schools was employed for Wave 2. RESULTS: The HCS successfully
      obtained approval from 149 school districts and 478 schools in 130 communities,
      recruited 5138 families, and interviewed 1421 key informants to allow for
      characterization of overall intensity of obesity prevention/treatment efforts in
      each community. CONCLUSIONS: Lessons learned are presented. Future studies should
      plan for inclusion of the following in development of recruitment strategies:
      literature review, formative research, pilot testing, and ongoing monitoring and
      adjustment.

PMID- 30209891
TI  - Post-treatment urinary sarcosine as a predictor of recurrent relapses in patients
      with prostate cancer.
AB  - To date, there has been no evidence regarding the association between urinary
      sarcosine content and prostate cancer survival. Our main objective was to
      investigate whether levels of post-treatment urinary sarcosine are associated
      with relapse. The inclusion criteria were (in accordance with EAU 2017) as
      follows: histopathologically verified adenocarcinoma in prostate biopsy cores or
      specimens from transurethral resection of the prostate (TURP) or prostatectomy
      for benign prostatic enlargement (BPE) with retained ability to urinate. The
      median follow-up was 53 months. In the study, we retrospectively evaluated a
      cohort of 511 patients with prostate cancer with various risk factors and
      treatment strategies. Post-treatment sarcosine levels were elevated in 266 (52%)
      patients and highly elevated (>=200 nmol/L) in 71 (13%) patients. Urinary
      sarcosine content was significantly associated with number of relapses that
      patients experienced, P = 0.002 for sarcosine >=200 vs <=30 nmol/L. Multivariate
      analysis revealed that sarcosine was an independent predictor of recurrent
      relapses (>=2 relapses with an intermediate period of remission), HR = 3.89 (95%
      CI 1.29-11.7) for sarcosine >200 vs <30 nmol/L. This trend was even more
      pronounced in a subgroup of patients who underwent radical prostatectomy, HR =
      3.29 (95% CI 1.06-10.18), where (single) relapse-free survival could also be
      predicted by sarcosine levels, HR = 1.96 (1.05-3.66). Urinary sarcosine may
      become a possible predictor for patients' outcomes, because patients with
      elevated post-treatment sarcosine could be predicted to have recurrent relapses
      of the disease.

PMID- 30209892
TI  - MicroRNA-451a acts as tumor suppressor in cutaneous basal cell carcinoma.
AB  - BACKGROUND: Basal cell carcinoma (BCC) is the most common type of skin cancer.
      The underlying mechanism leading to BCC formation is not fully uncovered. The aim
      of this study was to characterize miRNA-451a as a novel tumor suppressor in
      cutaneous BCC. METHODS: We first evaluated miRNA-451a level in human BCC clinical
      tissues and inducible BCC mouse model. Then we studied the impact of
      overexpressing or inhibiting miR-451a in cell proliferation, colony formation
      potential, and cell cycle pattern. Next, we employed luciferase reporter assay
      and western blotting to evaluate TBX1 as a downstream target of miRNA-451a.
      Lastly, we confirmed TBX1 expressional change in BCC tissues by qPCR. RESULTS:
      miRNA-451a was significantly reduced in human BCC tissues. The downregulation of
      miRNA-451a was also confirmed in BCC mouse model. Overexpressing miRNA-451a in
      tumor cells markedly suppressed cell growth through G1 cell cycle arrest.
      However, inhibiting miRNA-451a in primary cells promoted cell growth and colony
      formation capacity. TBX1 (602054) was predicted as a downstream target of miRNA
      451a and this was confirmed by luciferase assay and protein expression. Finally,
      TBX1 level was shown upregulated in BCC tissues as inversely to miR451a.
      CONCLUSION: Our studies revealed that miRNA-451a/TBX1 axis played a pivotal role
      in BCC tumorigenesis.

PMID- 30209893
TI  - Clinicopathological characteristics and prognosis of thyroid cancer in northwest
      China: A population-based retrospective study of 2490 patients.
AB  - BACKGROUND: The specific clinical features of thyroid cancer patients in
      northwest China are unclear; therefore, we analyzed the clinicopathological
      characteristics and prognosis of this population. METHODS: Clinical
      characteristics including age, gender, blood type, histological type, and
      BRAFV600E gene mutation; and incidence; risk factors; surgical treatment; and
      prognosis were recorded. RESULTS: A total of 2490 thyroid cancer patients were
      included; 98% were diagnosed with papillary thyroid cancer (PTC). Weight, blood
      type, histological type, and BRAFV600E gene mutation rates were significantly
      different. Pediatric thyroid cancer patients had higher lymph node metastasis,
      lower BRAFV600E mutation, and 6.2-9.2% greater recurrence rates than adult
      patients. PTC and papillary thyroid microcarcinoma displayed similar features,
      while in other types, such as follicular and medullary thyroid cancer, there were
      variations. Multiple logistic analyses showed that age (odds ratio [OR] 0.957,
      95% confidence interval [CI] 0.944-0.970; P < 0.001), focal status (OR 16.174,
      95% CI 9.257-28.262; P < 0.001), pathology (OR 0.642, 95% CI 0.473-0.871; P =
      0.004) and lymph node metastasis (OR 0.059, 95% CI 0.033-0.107; P < 0.001) were
      independent factors for BRAFV600E mutation. CONCLUSION: Most real world
      clinicopathological features, treatment, and prognosis of thyroid cancer are
      similar to reported data, such as the higher incidence of disease in women and
      the larger proportion of PTC. However, the results in pediatric patients and
      those with BRAF gene mutations are controversial and require more clinical
      incidence.

PMID- 30209894
TI  - PTBP1 acts as a dominant repressor of the aberrant tissue-specific splicing of
      ISCU in hereditary myopathy with lactic acidosis.
AB  - BACKGROUND: Hereditary myopathy with lactic acidosis (HML) is an autosomal
      recessive disease caused by an intron mutation in the iron-sulfur cluster
      assembly (ISCU) gene. The mutation results in aberrant splicing, where part of
      the intron is retained in the final mRNA transcript, giving rise to a truncated
      nonfunctional ISCU protein. Using an ISCU mini-gene system, we have previously
      shown that PTBP1 can act as a repressor of the mis-splicing of ISCU, where
      overexpression of PTBP1 resulted in a decrease of the incorrect splicing. In this
      study, we wanted to, in more detail, analyze the role of PTBP1 in the regulation
      of endogenous ISCU mis-splicing. METHODS: Overexpression and knockdown of PTBP1
      was performed in myoblasts from two HML patients and a healthy control.
      Quantification of ISCU mis-splicing was done by qRTPCR. Biotinylated ISCU RNA,
      representing wildtype and mutant intron sequence, was used in a pull-down assay
      with nuclear extracts from myoblasts. Levels of PTBP1 in human cell lines and
      mice tissues were analyzed by qRTPCR and western blot. RESULTS: PTBP1
      overexpression in HML patient myoblasts resulted in a substantial decrease of
      ISCU mis-splicing while knockdown of PTBP1 resulted in a drastic increase. The
      effect could be observed in both patient and control myoblasts. We could also
      show that PTBP1 interacts with both the mutant and wild-type ISCU intron
      sequence, but with a higher affinity to the mutant sequence. Furthermore, low
      levels of PTBP1 among examined mouse tissues correlated with high levels of
      incorrect splicing of ISCU. CONCLUSION: Our results show that PTBP1 acts as a
      dominant repressor of ISCU mis-splicing. We also show an inverse correlation
      between the levels of PTBP1 and ISCU mis-splicing, suggesting that the high level
      of mis-splicing in the skeletal muscle is primarily due to the low levels of
      PTBP1.

PMID- 30209895
TI  - The impact of Middle Eastern Origin, HIV, HCV, and HIV/HCV co-infection in the
      development of hypovitaminosis D in adults.
AB  - BACKGROUND: A relationship between hypovitaminosis D and infection with HIV and
      HCV has been established in the scientific literature. Studies comparing these
      illnesses to other risk factors for development of hypovitaminosis D, such as
      being of Middle Eastern origin, have been lacking. The goals of this study were:
      (a) to document vitamin D levels in groups of individuals at high risk of
      developing its deficiency, (b) analyze the data collected to numerically
      determine which group had the lowest average vitamin D levels, and (c) discuss
      the impact of the findings and offer possible explanations. METHODS: This
      retrospective observational study involved reviewing medical charts and
      documenting recent vitamin D levels. Our subgroups were: (a) individuals infected
      with HIV, (b) individuals infected with HCV, (c) individuals co-infected with
      HIV/HCV, and (d) people of Middle Eastern origin. The gathered data was
      subsequently subjected to statistical analysis. RESULTS: People of Middle Eastern
      origin were found more likely to be vitamin D deficient as compared to those
      infected with HIV, HCV, or co-infected with both HIV and HCV. CONCLUSION: This
      suggests that genetic and environmental factors unique to otherwise healthy
      Middle Eastern people are more detrimental, in terms of developing
      hypovitaminosis D, than being chronically infected with the aforementioned
      illnesses.

PMID- 30209896
TI  - Finasteride and Erectile Dysfunction in Patients with Benign Prostatic
      Hyperplasia or Male Androgenetic Alopecia.
AB  - Finasteride is primarily used to treat benign prostatic hyperplasia (BPH) and
      male androgenetic alopecia (MAA). Five-alpha reductase inhibitors (5alpha-RIs)
      could induce male sexual dysfunction due to their effects on testosterone and
      dihydrotestosterone. There is evidence suggesting that 5alpha-RIs may
      independently increase the risk of erectile dysfunction (ED). However, many
      investigators believe that side effects of 5alpha-RIs will disappear with
      continuous treatment. Considerable controversy exists regarding the severity and
      persistence of side effects of finasteride on ED. The aim of this review was to
      summarize current research studies on finasteride associated with ED. The search
      strategy used each term of finasteride and ED against PubMed database to identify
      related studies. ED data reported from available trials for finasteride were
      summarized and reviewed. Although there is not enough evidence to prove the
      relationship between finasteride and ED, most studies in this review found that
      finasteride for BPH was correlated with ED. However, most studies included in
      this review revealed that finasteride for MAA was not correlated with ED. On the
      other hand, some studies reported side effects of finasteride associated with
      sexual dysfunction, including ED, male infertility, ejaculation problem, and loss
      of libido, even in MAA patients. Well-designed randomized controlled trials are
      needed to further determine the mechanism and effects of finasteride on ED.
      However, physicians should discuss with their patients possible long-term effects
      of finasteride on sexual function, although we do not have evidence showing that
      adverse events of sexual dysfunction are absolutely associated with 5alpha-RIs.

PMID- 30209897
TI  - Sleep, Sleep Disorders, and Sexual Dysfunction.
AB  - Good sleep is necessary for good health. Sleep health is increasingly recognized
      as important for physical and mental health by both the medical profession and
      the general public, and there is great interest in how to avoid and treat sleep
      disorders and problems. Recent research indicates that insufficient sleep,
      disrupted sleep, and sleep disorders affect many aspects of human health
      including sexual function. In fact, patients with urological disorders or
      erectile dysfunction (ED) may have a sleep disorder that contributes to their
      urological or sexual dysfunction. Obstructive sleep apnea, insomnia, shift work
      disorder, and restless legs syndrome are all common sleep disorders and are
      associated with ED and/or other urological disorders. Therefore, careful
      attention should be paid to the diagnosis and treatment of concomitant sleep
      disorders in patients with sexual dysfunction. In this review, we provide an
      overview of what sleep is and how it is assessed in the clinic or laboratory; our
      current understanding of the functions of sleep and sleep health; a description
      of common sleep disorders, as well as how they are diagnosed and treated; and how
      sleep and its disorders are associated with male sexual dysfunction. Sleep is
      considered to be a 'third pillar of health', along with diet and exercise. With
      an understanding of common sleep disorders and how they can impact male sexual
      function, the urologist can ensure that sleep disorders are considered as a
      contributor to sexual dysfunction in their patients in order to provide them with
      the optimal treatment for overall health.

PMID- 30209898
TI  - Microsurgical Denervation of Spermatic Cord for Chronic Idiopathic Orchialgia:
      Long-Term Results from an Institutional Experience.
AB  - PURPOSE: Chronic testicular pain remains an important challenge for urologists.
      At present there are many treatment modalities available for chronic orchialgia.
      Some patients remain in pain despite a conservative treatment. Microsurgical
      denervation of spermatic cord appears to be successful in relieving pain in
      patients who fail conservative management. We assessed the long-term efficacy,
      complications and patient perceptions of microsurgical denervation of the
      spermatic cord in the treatment of chronic orchialgia. MATERIALS AND METHODS: A
      prospective study was conducted from January 2007 to January 2016 which included
      men with testicular pain of >3 months duration, failure of conservative
      management, persistent of pain for >3 months after treating the underlying cause.
      Total 48 patients with 62 testicular units (14 bilateral) showed the response to
      spermatic cord block and underwent Microsurgical Denervation of Spermatic Cord.
      RESULTS: Out of 62 testicular units (14 bilateral) which were operated, complete
      2 years follow-up data were available for 38 testicular units. Out of these 38
      units, 31 units (81.57%) had complete pain relief, 4 units (10.52%) had partial
      pain, and 3 units (7.89%) were non-responders. Complications were superficial
      wound infection in 3 units (4.83%), hydrocele in 2 units (3.22%), subcutaneous
      seroma in 2 units (3.22%), and an incisional hematoma in 1unit (1.61%) out of 62
      operated testicular units. CONCLUSIONS: Idiopathic chronic orchialgia remains a
      difficult condition to manage. If surgery is considered, microsurgical
      denervation of spermatic cord should be considered as a first surgical approach
      to get rid of pain and sparing the testicle.

PMID- 30209899
TI  - Role of Androgen Receptor in Prostate Cancer: A Review.
AB  - Androgen receptor (AR) is a steroid receptor transcriptional factor for
      testosterone and dihydrotestosterone consisting of four main domains, the N
      terminal domain, DNA-binding domain, hinge region, and ligand-binding domain. AR
      plays pivotal roles in prostate cancer, especially castration-resistant prostate
      cancer (CRPC). Androgen deprivation therapy can suppress hormone-naive prostate
      cancer, but prostate cancer changes AR and adapts to survive under castration
      levels of androgen. These mechanisms include AR point mutations, AR
      overexpression, changes of androgen biosynthesis, constitutively active AR splice
      variants without ligand binding, and changes of androgen cofactors. Studies of AR
      in CRPC revealed that AR was still active in CRPC, and it remains as a potential
      target to treat CRPC. Enzalutamide is a second-generation antiandrogen effective
      in patients with CRPC before and after taxane-based chemotherapy. However, CRPC
      is still incurable and can develop drug resistance. Understanding the mechanisms
      of this resistance can enable new-generation therapies for CRPC. Several
      promising new AR-targeted therapies have been developed. Apalutamide is a new
      Food and Drug Administration-approved androgen agonist binding to the ligand
      binding domain, and clinical trials of other new AR-targeted agents binding to
      the ligand-binding domain or N-terminal domain are underway. This review focuses
      on the functions of AR in prostate cancer and the development of CRPC and
      promising new agents against CRPC.

PMID- 30209900
TI  - Long-Term Testosterone Therapy in Type 2 Diabetes Is Associated with Decreasing
      Waist Circumference and Improving Erectile Function.
AB  - PURPOSE: To describe the 4-year metabolic follow-up results from the BLAST study.
      MATERIALS AND METHODS: Baseline hemoglobin A1c (HbA1c), weight, and waist
      circumference (WC) data were recorded in 185 men recruited for the BLAST
      randomised controlled trial (RCT) and erectile function (EF) scores were also
      available in an additional 48 men screened for the RCT. Intra/inter-group
      associations between these parameters and testosterone replacement therapy (TRT)
      were assessed at 1) end of the RCT (30 weeks), 2) open-label phase (82 weeks),
      and 3) final assessment via non-parametric statistics. RESULTS: Improvement in
      HbA1c and weight at the end of the RCT and open-label phase in men on TRT was not
      maintained long-term. The convergence in HbA1c could have been due to
      incentivised care with HbA1c targets. Interestingly those on TRT at final
      assessment required fewer anti-diabetic agents. The weight increase in routine
      care may have been due to changes in diabetes medication or an increase in lean
      muscle mass. WC continued to decrease in men on TRT indicating possible reduction
      in visceral fat. Improvement in EF scores continued with long-term TRT, this was
      abolished when TRT was discontinued. CONCLUSIONS: This study hints at benefits in
      glycaemic control, weight and WC, and long-term RCTs studying mechanisms of
      benefit and clinical outcomes are necessary. Our results also show that EF scores
      continued to improve with long-term TRT, even beyond the 6 months that we
      previously reported in the BLAST RCT.

PMID- 30209901
TI  - [Prevention of prolonged opioid use after surgery].
AB  - In the last decade, the number of opioid users in the Netherlands is sharply
      increasing. Opioids are the cornerstone of postoperative pain management. The
      postoperative period is therefore an important period to be aware of needless and
      possible persistent opioid use. Identification of patients at risk for persistent
      opioid use, limitation of opioid prescriptions and clear guidelines and
      communication about the follow-up of postoperative pain will be necessary to
      prevent opioid misuse. Awareness of the above-mentioned measures will hopefully
      help to stop further growth of opioid use, and thereby avert an American
      scenario.

PMID- 30209902
TI  - [Selection for medical school fairer than lottery? Not at all].
AB  - In 2014, the random selection (or lottery) admission process was replaced by a
      decentralised selection procedure for all medical schools in the Netherlands. The
      argument behind this change is that it should lead to a better match between
      candidate and study. Also, at introduction some reasoned that this new procedure
      would be fairer. However, several recent studies show no evidence that a
      decentralised selection procedure outperforms the replaced lottery system when
      motivation and study results are considered. Furthermore, medical schools use
      their own, wide varying selection criteria, whilst having the same goal:
      selecting the best future doctors. Next to this, future students can only apply
      for one medical school each year. Medical schools show significant difference in
      the number of applications, which therefore leads to different odds of a student
      being admitted (e.g. 27 vs. 62% admission rate at most and least popular medical
      schools). To make the selection procedure for admission to medical school fairer,
      central selection for all medical schools or the option to apply at multiple
      medical schools each year should be considered - particularly since these are
      well-known aspects of the selection procedures in other countries.

PMID- 30209903
TI  - [Sexual dysfunction as a side effect of medication].

PMID- 30209905
TI  - [Xanthones from Rhizoma of Securidaca inappendiculata].
AB  - Objective: To study the chemical constituents of Securidaca inappendiculata.
      Methods: The chemical constituents were isolated and purified by chromatography
      on silica gel, Sephadex LH-20 columns. Their structures were elucidated by means
      of physicochemical properties and spectroscopic analysis. Results: Ten compounds
      were identified from the dichloromethane fraction of Securidaca inappendiculata,
      and identified as 1,7-dihydroxyxanthone (1), 1,3,8-trihydroxy-2-methoxyxanthone
      (2), 1,7-dihydroxy-3,4-dimethoxyxanthone (3), 1,3,8-trihydroxy-4-methoxyxanthone
      (4), 7-hydroxy-1,2-dimethoxyxanthone (5), 1,3,6-trihydroxy-2,7-dimethoxyxanthone
      (6), 1,4, 8-trihydroxyxanthone (7), 1,7-dihydroxy-3-methoxyxanthone (8), 1,6
      dihydroxy-7-methoxyxanthone (9) and 1,8-dihydroxy-3,4-dimethoxyxanthone (10).
      Conclusion: Compounds 7-10 are isolated from this plant for the first time, and
      compounds 7-10 are isolated from this genus for the first time.

PMID- 30209904
TI  - [Study on the Flavonoids and Biological Activity of Rubus sachalinensis].
AB  - Objective: To study the chemical constituents and biological activity of Rubus
      sachalinensis. Methods: The compounds in the ethyl acetate and n-butanol fraction
      were isolated and purified by macroporous resin,Sephadex LH-20 column
      chromatography,and reverse-phase preparative HPLC. The structures were identified
      by various spectroscopic data such as 1D,2D-NMR,HRMS. Antioxidant,anti
      inflammatory and cytotoxicity of the compounds were determined by FRAP,Griess and
      MTT methods. Results: Eight compounds were isolated from the ethyl acetate and n
      butanol extract of Rubus sachalinensis,and identified as kaempferol-3-O-beta-D
      butyl glucuronate( 1),quercetin-3-O-beta-D-butyl glucuronate( 2),quercetin-3-O
      beta-D-glucopyranoside( 3),cis-tiliroside( 4),tiliroside( 5),quercetin-3-O-beta-D
      ethyl glucuronate( 6),quercetin( 7) and kaempferol( 8). Activity assay showed
      that the compounds 1 ~ 8 had different levels of antioxidant activity,all the
      compounds showed cytotoxicities of IC50 greater than 200 MUmol / L. Conclusion:
      Flavonoids are the main antioxidant consitituents of Rubus sachalinensis and have
      a good anti-inflammatory activity. All the compounds are isolated from this plant
      for the first time,compounds 1,2,6 are obtained from the this genus for the first
      time.

PMID- 30209906
TI  - [Chemical Constituents of Alkaloids from the Bark of Sophora japonica].
AB  - Objective: To study the chemical constituents in the bark of Sophora japonica.
      Methods: The chemical constituents were separated and purified by silica
      gel,Sephadex LH-20 column chromatography,and HPLC. Their structures were
      identified by various spectroscopic analyses. Results: Eleven compounds were
      obtained from the bark of Sophora japonica. Their structures were identified as(
      +)-oxymatrine( 1),isosophoridine( 2),lupanine( 3),( +)-matrine( 4),( +)
      sophoramine( 5),(-)-14beta-hydroxymatrine( 6),(-)-7,11-dehydromatrine(
      7),alopecurin A( 8),( +)-sophoranol( 9),alpha-isolupanine( 10) and( +)
      allomatrine( 11). Conclusion: Compounds 2,3,5 and 7 ~ 11 are isolated from this
      plant for the first time.

PMID- 30209907
TI  - [Chemical Constituents of Lonicerae Japonicae Flos].
AB  - Objective: To study the chemical constituents of the methylene chloride extract
      of Lonicerae Japonicae Flos. Methods: The compounds were isolated and purified by
      silica gel column chromatography,Sephadex LH-20 gel column chromatography and
      recrystallization. The structures were elucidated by the physical and chemical
      properties,MS,1H-NMR and13C-NMR spectroscopy. Results: Nine compounds were
      isolated and their structures were identified as beta-sitosterol( 1),benzoic
      acid( 2),5-hydroxy-7,3',4'-trimethoxyflavone( 3),tetrapedic acid B( 4),tricin(
      5),hydnocarpin D( 6),6,7,10-trihydroxy-8-octadecenoic acid( 7),5'
      methoxyhydnocarpin-D( 8) and daucosterol( 9). Conclusion: Compound 2,4,7,8 are
      isolated from this plant,compounds 2,7,8 are isolated from Caprifoliaceae family
      for the first time.

PMID- 30209908
TI  - [A Study on the Antibacterial Material Basis of Polygonum capitatum by Spectrum
      effect Relationship].
AB  - Objective: To clarify the antibacterial material basis of Polygonum capitatum.
      Methods: D101 macroporous resin and MCI column chromatographic methods were used
      for the preparation of various fractions,while UHPLC-UV methods were used to
      establish the chromatogram for the fractions, and the chromatographic peaks were
      identified by comparing their retention times and UV spectra with the authentic
      standards; uniform design was adopted for the preparation of samples with
      different peak concentrations,and their antibacterial effects were evaluated by
      determining their MIC against Escherichia coli,the bacterium generally found in
      urinary tract infections. Grey relational analysis was employed to investigate
      the relationship between the 1 / MIC values and the peak areas and to reveal the
      antibacterial material basis of Polygonum capitatum. Results: Peaks 1( gallic
      acid),6( epicatechin),8( catechin),13( rutin),17( quercetin-3-O-( 2"-O-galloyl)
      beta-D-glucopyranoside) and 18( quercetin) showed a better correlation( grey
      relational grades were higher than 0. 8) to the antibacterial activity.
      Conclusion: The antibacterial activity of Polygonum capitatum is attributed to
      the holistic effects of most of the constitutional compounds,and gallic
      acid,epicatechin,catechin,rutin,quercetin-3-O-( 2"-O-galloyl)-beta-D
      glucopyranoside and quercetin are the main antibacterial material basis of
      Polygonum capitatum. This study forms a strong basis for the quality control and
      exploitation of Polygonum capitatum and its products.

PMID- 30209909
TI  - [HPLC Fingerprint and Determination in the Root of Amorpha fruticosa].
AB  - Objective: To establish HPLC fingerprint in the root of Amorpha fruticosa, and
      simultaneously to determine the content of calycosin-7-O-beta-D-glucopyranoside,
      ononin, calycosin, formononetin. Methods: The analytical column was Diamonsil
      C18( 250 mm *4. 6 mm,5 MUm). The mobile phase was acetonitrile( A)-water( B)(
      containing 0. 2% phosphoric acid) in gradient elution, and the detection
      wavelength was set at 260 nm. "Chromatographic fingerprint similarity evaluation
      software "version( 2004A) was used to evaluate similarity for the ten batches
      medicinal materials,and SPSS software was used for cluster analysis. Results: The
      HPLC fingerprint of the root of Amorpha fruticosa was established with good
      separation, and four chemical compositions were determinated. 16 common peaks
      were defined in the HPLC fingerprint among the 10 batches of the root of Amorpa
      fruticosa. The similarity among them was more than0. 90. Conclusion: This
      analytical method has strong features,with a good repeatability and the method is
      simple, which can be used efficiently in the quality control in the root of
      Amorpha fruticosa.

PMID- 30209910
TI  - [Comparative Study on the Four Kinds of Flavonoids from Four Different Varieties
      of Dendranthema morifolium].
AB  - Objective: To establish a high phase liquid chromatography method of the content
      in quercetin,luteolin,apigenin,acacetin,and to compare the difference of content
      from four different varieties of Dendranthema morifolium in simultaneously.
      Methods: The UPLC methods were adopted,and the chromatographic column was Waters
      ACQUITYUPLC?; the column was BEH C18( 50 mm *2. 1 mm,1. 7 MUm),the mobile phase
      was 0. 1% phosphoric acid solution-methanol in gradient elution,the flow rate was
      0. 2 m L/min;and the detection wavelength was set at 320 nm; the column
      temperature 25 C; and the sample quantity was 1 MUL. Results: In the range of 0.
      0027 0. 0135 mg/m L( r1= 0. 9962) concentration within quercetin in a good linear
      relationship between peak area. In the range of0. 0032 0. 0160 mg/m L( r2= 0.
      9963) concentration within luteolin in a good linear relationship between peak
      area. In the range of0. 0029 0. 0145 mg/m L( r3= 0. 9964) of apigenin in the mass
      concentration and the peak area. In the range of 0. 0029 0. 0145 mg/m L( r4= 0.
      9963) concentration within acacetin in a good linear relationship between peak
      area. Conclusion: This method can be determined daisy
      quercetin,luteolin,apigenin,acacetin content in Dendranthema morifolium.

PMID- 30209911
TI  - [Optimization of Supercritical Fluid Extraction of Total Flavonoids and Monomer
      Compositions from Taxus Remainder Extracts Free of Taxoids].
AB  - Objective: To optimize the supercritical fluid extraction technology of
      flavonoids from taxus remainder extracts free of taxoids( TREFT) by response
      surface methodology( RSM). Methods: By using a central composite design( CCD) in
      four factors and five levels to optimize the extraction parameters. The effects
      of extraction time, temperature, pressure and different concentration of ethanol
      and their interaction on the extraction rate of total flavonoids, amentoflavone,
      quercetin and ginkgetin which extracted from TREFT by supercritical fluid CO2
      were investigated. Results: Under optimal conditions of extraction time for 2. 2
      h,and the extraction temperature was 46. 4 C,the extraction pressure was 22. 6
      MPa, and 80. 7% ethanol, the index experimental of total flavonoids and monomer
      compositions was 98. 75. Conclusion: The process of flavonoids extraction from
      TREFT is stable and feasible, which can provide technical support for the
      resource utilization of TREFT.

PMID- 30209913
TI  - Update in Infectious Diseases 2018.
AB  - VIII Updating Course of Antimicrobials and Infectious Diseases has reviewed
      useful microbiological, epidemiological and clinical aspects for a current
      approach of infectious pathology. Present manuscript summarizes a chronicle about
      the main infection related meetings during 2017 (ECCMID, IAS, ASM and ID Week).
      In addition, the course proposed a practical approach for understanding different
      type of pathogens and our selected topics this year were the epidemiology of
      bacterial nosocomial infection, a practical approach to Clostridium difficile
      infection patients, a two year selection of the top ten papers about fungal
      infection and an update in fungal biofilms. Finally, proffesors made a practical
      approach by main clinical syndromes like sepsis, infections in oncohematological
      patients, CNS infections in immunosuppressed patients and reviewed the top ten
      papers in transplant infectious diseases and infection control during the last
      two years.

PMID- 30209912
TI  - [Sijunzi Decoction Promote the Repair of Intestinal Epithelial Cell Injury via
      Activating TLR-2/My D88 Signaling Pathway].
AB  - Objective: To study the effect and mechanism of Sijunzi decoction( SJZD)
      containing serum on the repairing of gastrointestinal mucosal damage. Methods:
      SJZD containing serum was prepared by serum pharmacological method. Cell
      migration model was established by tips scratch method, Real-time-cell-analyzer(
      RTCA) was used to mensurate IEC-6 cell proliferation, the mRNA and protein
      expression of TLR-2 and My D88 mRNA were detected by qRT-PCR and Western blot
      analysis,respectively. Results: Medium dose( 10%) and high dose( 20%) of SJZD
      containing serum stimulated IEC-6 cell migration at 8 h after cell damage; medium
      dose( 10%)and high dose( 20%) of SJZD containing serum increased IEC-6 cell
      proliferation at 12 h after cell damage; low dose( 5%),medium dose( 10%) and high
      dose( 20%) of SJZD containing serum enhanced IEC-6 proliferation both at 24 h and
      36 h after cell damage. Medium dose( 10%) and high dose( 20%) of SJZD containing
      serum upregulated TLR-2 and My D88 mRNA and protein expression,respectively.
      Conclusion: Sijunzi decoction can repair the injury of gastrointestinal mucosal
      barrier,the mechanism may be related to its effect on activating TLR-2 / My D88
      signaling pathway,and promoting IEC-6 cell migration and proliferation.

PMID- 30209914
TI  - Highlights at the 27th Congress of the European Society of Clinical Microbiology
      and Infectious Diseases, 2017.

PMID- 30209919
TI  - A comprehensive approach for the patient with Clostridium difficile infection.
AB  - During the last decade there have been many changes and advances in the research
      on Clostridium difficile infection (CDI). We have improved diagnostic and
      therapeutic tools and, at the same time, we have learned that the CDI implies,
      especially in the most vulnerable patients, an important morbidity. CDI has
      traditionally been undervalued and it is widely dispersed in hospitals. Surely,
      there is inertness in its management and there are also broad areas of
      improvement. If we add to this the high cost of the new drugs and the practical
      difficulties to implement the faecal microbiota transplant, we realize that we
      may not be taking full advantage of all the opportunities to improve patient's
      outcomes. The implementation of policies that favour the supervision of all CDI
      cases by an expert in infectious diseases will contribute to a better global
      management of this important disease.

PMID- 30209918
TI  - Changes in bacterial hospital epidemiology.
AB  - Antibiotics' use and prescription requires a profound review, as their inadequate
      administration has been one of the main forces leading to resistance as a result
      of overuse and misuse. Resistance is particularly challenging in nosocomial
      environments in which there has been a gradual change in bacterial epidemiology
      owing to the continuous increase of multi-drug-resistant isolates, which imply a
      threat to prevent and cure infections. Expertise at the time of using
      antibiotics, development of new diagnostic tools and the possibility of having
      new antimicrobials are required to stay ahead of evolving resistance. Moreover,
      surveillance is also relevant to monitor antimicrobial resistance.

PMID- 30209920
TI  - Top-ten papers in fungal infection (2015-2017).
AB  - We have clustered the published articles in fungal infection between 2016 and
      2017 in four categories. First, the emergence of Candida auris as a nosocomial
      pathogen associated to high antifungal resistance and high mortality. Second, the
      growing importance of fungal infections associated to the use of biologic
      therapies. Third, the approval of isavuconazole for the treatment of filamentous
      fungi and dymorphic mycoses with positive results and less side effects. And
      finally, a mix of other important news regarding empiric therapy, fluconazole
      toxicity and difficult-to-treat fungal infections..

PMID- 30209921
TI  - Fungal biofilms: From bench to bedside.
AB  - Biofilms cause recurrent invasive infections that are difficult to eradicate
      because of their high resistance to antimicrobials and host defence mechanisms.
      Fungal biofilm-related infections are associated with high mortality rates.
      Although current guidelines recommend catheter removal for catheter-related
      bloodstream infections due to Candida species, several studies have shown that
      the efficacy of the antifungal lock technique. The use of combinations of
      antifungal agents may improve the management of biofilm-related fungal infections
      and prevent the emergence of resistance associated with monotherapy. Since the
      presence of mixed bacterial-fungal biofilm infections is very prevalent, a
      combination of antibacterial and antifungal agents should be considered.

PMID- 30209922
TI  - Practical Decalogue in the management of sepsis.
AB  - Sepsis is a complex entity where there are still many controversies regarding
      diagnosis and therapeutic management. The present article pretends to review the
      recently published in relation to these disagreements and contains a proposal of
      practical approach to the infected patient.

PMID- 30209923
TI  - Usefulness of biomarkers on infection management: with or without them?
AB  - Infectious diseases are disorders caused by many different microorganisms that
      produce clinical conditions with a wide variation in patient-rated symptoms and
      severity. Therefore, different diagnostic and prognostic tools are needed to help
      make the most accurate decisions at each moment of patient's care with suspected
      infection. This mini review will analyse how some biomarkers reduce the level of
      uncertainty in the making decision process at some phases of sepsis, including
      prompt identification of septic patients, early initiation of empiric broad
      spectrum antimicrobials, regimen and duration.

PMID- 30209924
TI  - Top-ten infections in onco-hematological patients (2015-2017).
AB  - To choose the most relevant ten papers constitutes a challenge in several ways.
      We have elaborated this selection based on the papers we find to be most useful
      and ground-breaking for the clinician faced daily by the infectious problems in
      onco-hematological patients. The selection has been structured in four parts:
      bacterial infections, viral infections, fungal infections and infections related
      with new drugs in onco-hematological patients.

PMID- 30209925
TI  - Highlights in solid transplant infectious diseases 2015-2017.
AB  - Solid organ transplant recipients have an increased risk of developing infections
      due to the lifelong treatment with immunosuppressive drugs. Herein we review
      recent (2015-2017) and relevant published advances in the field of bacterial,
      viral and fungal-infections in this population. We also address the most up-to
      date immunological assays that can predict the risk of infection. Finally, we
      review current guidelines and how they improve the usual clinical care.

PMID- 30209926
TI  - Central nervous system infections in immunocompromised patients.
AB  - Diagnosis of CNS infections remains a great challenge in immunocompromised
      patients with solid cancer or hematological disorders, as it happens with
      transplant recipients, since symptoms might both be masked and be mimicked by
      other conditions such as metabolic disturbances or consequences of antineoplastic
      treatment and the administration of immunosuppressive drugs. Thus, awareness of
      this complication is crucial and any suspicion of a CNS infection should lead to
      make an early diagnosis and to choose an appropriate empirical treatment to
      improve the outcome in this population.

PMID- 30209927
TI  - Top-ten papers in Infection Control (2015-2017).
AB  - Healthcare-associated infections are a main Public Health challenge. In the era
      of antimicrobial resistance, more effective Infection Control Programs are
      needed. In this review we will discuss some publications related to hand hygiene
      (should the patients participate in the improvement programs?); some new
      strategies to enhance terminal room disinfection and important controversies on
      contact precautions policies (should we abandon them?). In the last year, there
      have been as well some reports that provide new insights in Clostridium difficile
      infection and in the impact of educational antimicrobial stewardship programs.

PMID- 30209928
TI  - [Sodium Aescinate Induced Apoptosis of BGC-823 and AGS Cells by Inhibiting JAK
      1/STAT-1 Signaling Pathway].
AB  - Objective: To investigate the mechanism of sodium aescinate on the apoptosis of
      gastric cancer BGC-823 cells and AGS cells. Methods: CCK-8 assay was used to
      detect the cell viability of cancer cells; cells morphological changes were
      observed by inverted microscope; changes in nuclear morphology were observed by
      fluorescence inverted microscope after DAPI staining; cells apoptosis rate was
      detected by flow cytometry; Western blotting was used to detected the
      phosphorylation of JAK-1 and STAT-1; laser confocal microscopy was used to
      observed the nuclear translocation of STAT-1. Results: Sodium aescinate inhibited
      cells proliferation in a concentration dependent manner, and changed the cells
      morphology and nuclear morphology, significantly up-regulated the apoptosis rate
      of gastric cancer BGC-823 cells and AGS cells, and down-regulated the
      phosphorylation of JAK-1, STAT-1 protein, inhibited the nuclear translocation of
      STAT-1. Conclusion: Sodium aescinate inhibit the proliferation and induce
      apoptosis in the gastric cancer BGC-823 cells and AGS cells, and this process can
      be implemented by inhibiting the JAK-1/STAT-1 signaling pathway.

PMID- 30209929
TI  - [Effects of the Saponins from Panax japonicus on Intestinal Epithelial Tight
      Junction Proteins in Aging Rats].
AB  - Objective: To investigate the moderating effects of total saponins of Panax
      japonicus on intestinal epithelial tight junction proteins in aging rats,and to
      explore the potential mechanism. Methods: SD rats were divided into adult group(
      6 months),old model group( 24 months),and different doses( 10,30 and 60 mg / kg)
      of total saponins of Panax japonicus treatment groups. Levels of tight junction
      proteins( Occludin and ZO-1),anti-oxidative pathway proteins( Nrf2,HO-1 and NQO
      1),mitochondrial biogenesis related proteins( Sirt1 and PGC-1alpha) and p-AMPK in
      the ileum were determined by immunohistochemistry staining. Results: Compared
      with adult group,the expressions of Occludin,ZO-1,Nrf2,HO-1,NQO-1,Sirt1 and PGC
      1alpha of aging rats were obviously decreased( P < 0. 01),and p-AMPK was
      inhibited in the ileum of aging rats. Compared with aging model rats,total
      saponins of Panax japonicus increased the expressions of Occludin,ZO-1,Nrf2,HO
      1,NQO-1,Sirt1 and PGC-1alpha( P < 0. 05 or P < 0. 01),and activated p-AMPK in the
      ileum of aging rats. Conclusion: The decreased level of intestinal tight junction
      proteins in the ileum of aging rats may be related to oxidative stress. Total
      saponins of Panax japonicus can up-regulate the level of intestinal tight
      junction proteins to improve the intestinal mucosal barrier dysfunction in the
      ileum of aging rat via reducing the levels of oxidative stress.

PMID- 30209930
TI  - [Study on the Mechanism of Yiqi Chutan Recipe in the Treatment of Lung Cancer
      with Splenasthenic Syndrome].
AB  - Objective: To investigate the mechanism of Yiqi Chutan recipe( YCR) in the
      treatment of lung cancer with splenasthenic syndrome from the perspective of the
      endoplasmic reticulum stress( ERS). Methods: 60 mice were successfully modeled as
      Lewis lung cancer mice with spleen deficiency, which were randomly divided into
      model group( normal saline),cisplatin group( 1 mg / kg),low dose( 2 g/kg) YCR
      group, middle dose( 4 g/kg) YCR group,high dose( 8 g/kg) YCR group and the
      combined medication group( YCR 4 g/kg + cisplatin 1 mg / kg),with 10 mice in each
      group. The mice were killed after 14 days,the size and weight of tumor in mice
      were measured,morphological changes of tumor were observed by HE staining method,
      the expression of CHOP and DR5 protein in tumor tissue was detected by
      immunohistochemical method and Western blot method. Results: Compared with model
      group, the volume and weight of tumor in cisplatin group, middle dose YCR group,
      high dose YCR group and combined medication group were significantly decreased( P
      < 0. 01),and the tumor cells in transplanted tumor were large necrosis and the
      protein expression of CHOP and DR5 were increased significantly( P < 0. 01). The
      effect in treatment of lung cancer with splenasthenic syndrone in combined
      medication group was higher( P < 0. 05 or P < 0. 01). Conclusion: Yiqi Chutan
      recipe has different degrees of inhibition on lung cancer, the combined use of
      cisplatin can obviously improve the curative effect. The mechanism may be related
      to up-regulating the expression of CHOP and DR5 in endoplasmic reticulum stress
      related proteins.

PMID- 30209931
TI  - [Antimicrobial stewardship programme implementation in a medical ward].
AB  - OBJECTIVE: Antimicrobial stewardship programmes (ASP) have proven to be effective
      tools for reducing the use of antimicrobials. The purpose of the study is to
      evaluate the effect of an ASP implantation in a medical Ward. METHODS:
      Prospective intervention study in a medical ward with a heterogeneous
      composition. In September 2014, an ASP based on prospective audits was
      implemented. Antimicrobial consumption and the length of stay and mortality in
      all patients admitted, as well as in the main infections present in the unit,
      were compared before and after two years of the ASP implementation. RESULTS: A
      total of 378 infectious episodes of 335 pa-tients were evaluated in 168 meetings.
      The prescriber ac-cepted 92.3% of the suggestions. The consumption of an
      timicrobials reviewed was reduced from 31.3 to 17.6 DDD / 100-stays (beta =-0.40,
      P = 0.015). The average cost per income was reduced from ? 161.4 to ? 123.3 (
      23.6%). No differences were found in total length of stay or mortality. There
      were no changes in the incidence of Clostridium difficile infection or candidemia
      between the two periods. There were no significant differences in length of stay
      or mortality in total bacteremia, candidemia, and urinary tract infections caused
      by multiresistant bacteria. CONCLUSIONS: The implementation of an ASP in a
      heterogeneous medical ward significantly reduces the use of antimicrobials in a
      short time horizon without adversely affecting the evolution of the patients..

PMID- 30209932
TI  - [Towards the empirical treatment of choice in anaerobic infections].

PMID- 30209934
TI  - The Tumor Lysis Syndrome.

PMID- 30209933
TI  - [Protective Effects of Angelica sinensis Volatile Oil on Atherosclerosis in
      Hyperlipidemia Mice].
AB  - Objective: To study the protective effects of Angelica sinensis volatile oil on
      atherosclerosis in hyperlipidemia mice. Methods: 60 mice were randomly divided
      into normal control group, model group, fluvastatin group, and high-, medium- and
      low-dose groups of Angelica sinensis volatile oil. Normal control group were fed
      with normal diet, the other groups were fed with high fat diet, and treated
      orally Vitamin D3 (100 million IU/kg) daily for 42 d. At the 14th day after
      modeling, fluvastatin group were orally administrated fluvastatin (6.7 mg /kg),
      and high-, medium- and low-doses of Angelica sinensis volatile oil groups were
      orally administrated Angelica sinensis volatile oil (40, 20, 10 mg /kg) for 28 d,
      and the normal control group and model group were administrated equal volume
      normal saline. The activity state, body weight and the levels of TC, TG, HDL-C
      and LDL-C in serum were measured. The atherosclerosis indexes (AI1, AI2),
      coronary heart index (R-CHR) were calculated. After the mice were killed, the
      heart, liver and abdominal aortas were taken. The mass of the heart and liver
      were measured, and the organ indexes were calculated; the tissues were fixed by
      formalin, embedded in paraffin, sliced, HE stained, and the histopathology
      changes were observed by microscope. Results: Compared with normal control group,
      the body weight of mice in the model group were decreased (P<0.01), and the
      heart, liver indexes were significantly increased (P<0.05), the levels TC, TG,
      LDL-C and HDL-C in serum and AI1, AI2 and R-CHR were significantly increased
      after modeling 42 d (P < 0.01). Compared with the model group, the mice body
      weight were significantly increased, and the heart, liver index were
      significantly decreased (P<0.05) in the high-, middle-dose group of Angelica
      sinensis volatile oil groups; the TC, TG and LDL-C levels were significantly
      decreased in low-dose group (P<0.05 or P<0.01); AI1 and R-CHR were significantly
      decreased (P<0.05 or P<0.01) in all Angelica sinensis volatile oil groups, but
      the AI2 in the high-dose group of Angelica sinensis volatile oil was
      significantly decreased (P<0.05). The histopathology results showed that Angelica
      sinensis volatile oil could relieve the fatty degeneration of hepatic cells and
      the injury of thoracic aortic intimae, and myocardial fibrosis, which could
      inhibit the formation of atherosclerotic plaque. Conclusion: The certain
      protective effects of Angelica sinensis volatile oil are determinated on
      atherosclerosis in hyperlipidemia mice.

PMID- 30209936
TI  - Cluster-Based Metal-Organic Frameworks: Modulated Singlet-Triplet Excited States
      and Temperature-Responsive Phosphorescent Switch.
AB  - Luminescent metal-organic frameworks (MOFs) have received much attention due to
      their applications in color displays, sensors, and smart materials. However, how
      to balance the energy distribution between singlet and triplet excited states for
      a new generation of persistent luminescent MOFs is still a challenging goal. In
      this work, we report that the construction of cluster-based MOFs can supply an
      effective way to modulate the fluorescence and room-temperature phosphorescence
      (RTP) emission based on adjustable pi-pi stacking, halogen-bonding interaction,
      and metal-cluster units. Compared to the pristine ligand (5-bromoisophthalic
      acid) with obvious spin-orbit coupling, Zn5 and Zn3 cluster-based MOFs exhibit
      tunable photoluminescence (such as fluorescence and RTP wavelength, lifetime, and
      quantum yield). The ultralong-lived RTP visualization and temperature-dependent
      luminescence also provide the Zn5 cluster-based MOF as a new type of
      anticounterfeiting and temperature-responsive phosphorescent switch material.
      Therefore, this work highlights the first example of cluster-based MOFs as
      ultralong-lived persistent luminescent materials for tuning singlet and triplet
      excited states, which may be extended to other similar systems for developing
      ultralong RTP and delayed fluorescence materials.

PMID- 30209935
TI  - Copper(II) Complexes with Bulky N-Substituted Diethanolamines: High-Field
      Electron Paramagnetic Resonance, Magnetic, and Catalytic Studies in Oxidative
      Cyclohexane Amidation.
AB  - The novel coordination compounds [Cu2(H tBuDea)2(OAc)2] (1) and [Cu2(H
      nBuDea)2Cl2]. nH2O (2) have been prepared through the reaction of the respective
      copper(II) salts with N- tert-butyldiethanolamine (H2 tBuDea, for 1) or N
      butyldiethanolamine (H2 nBuDea, for 2) in methanol solution. Crystallographic
      analysis reveals that, in spite of the common binuclear {Cu2(MU-O)2} core, the
      supramolecular structures of the complexes are drastically different. In 1
      binuclear molecules are linked together by H-bonds into 1D chains, while in 2 the
      neighboring pairs of binuclear molecules are H-bonded, forming tetranuclear
      aggregates. Variable-temperature (1.8-300 K) magnetic susceptibility measurements
      of 1 and 2 show a dominant antiferromagnetic behavior. Both complexes are also
      studied by HF-EPR spectroscopy. While the interaction between Cu(II) centers in 1
      can be described by a single coupling constant J = 130.1(3) cm-1 (using H = JS1
      S2), the crystallographically different {Cu2(MU-O)2} pairs in 2 are expected
      exchange from ferro- to antiferromagnetic behavior (with J ranging from -32 to
      110 cm-1, according to DFT calculations). Complexes 1 and 2 act as catalysts in
      the amidation of cyclohexane with benzamide, employing tBuOO tBu as oxidant. The
      maximum achieved conversion of benzamide (20%, after 24 h reaction time) was
      observed in the 1/ tBuOO tBu system. In the cases of tBuOO(O)CPh or tBuOOH
      oxidants, no significant amidation product was observed, while for tBuOO(O)CPh,
      the oxidative dehydrogenation of cyclohexane occurred, giving cyclohexene, to
      afford the allylic ester (cyclohex-2-en-1-yl benzoate) as the main reaction
      product.

PMID- 30209937
TI  - High Proton Mobility with High Directionality in Isolated Channels of MOF-74.
AB  - Isolated one-dimensional (1-D) proton channels in a metal-organic framework, MOF
      74, have been reasonably expected to show highly directional proton conductivity,
      although no evidence has been provided. As a result of dimensional anisotropy of
      the channels evenly aligned in the c-axis of MOF-74 single crystal, highly
      directional proton conductivity is demonstrated by using electrochemical
      impedance spectroscopy. In particular, single crystals treated with sulfuric acid
      or ammonium hydroxide displays a maximum ~1200-fold-enhanced c-axis proton
      conductivity compared to its a-axis conductivity, demonstrating highly
      directional proton migration through the channels. Very low activation energies
      (e.g., 0.12 eV) for the c-axis conductivity of MOF-74 also suggest a high proton
      mobility that arises via Grotthuss proton transfer parallel to the channels.

PMID- 30209938
TI  - New Method for Accurate Determination of Polyphenol Oxidase Activity Based on
      Reduction in SERS Intensity of Catechol.
AB  - Rapid and accurate measurement of polyphenol oxidase (PPO) activity is important
      in the food industry as PPOs play a vital role in catalyzing enzymatic reactions.
      The aim of this study was to develop surface-enhanced Raman scattering (SERS)
      approach for accurate determination of PPO activity in fruit and vegetables using
      the reduction in SERS intensity of catechol in reaction medium. Within a certain
      catechol concentration, when a purified PPO solution was analyzed, the reduction
      in SERS intensity (Delta I) was linear to PPO activity ( Ec) in a wide range of
      500-50 000 U/L, and a linear regression equation of log Delta I/Delta t = 0.6223
      log Ec + 0.8072, with a correlation coefficient of 0.9689 and a limit of
      detection of 224.65 U/L, was obtained. The method was used for detecting PPO
      activity in apple and potato samples, and the results were compared with those
      obtained from colorimetric assay, which demonstrated that the proposed method
      could be successfully used for detecting PPO activity in food samples.

PMID- 30209939
TI  - Facile and Scalable Approach To Fabricate Granadilla-like Porous-Structured
      Silicon-Based Anode for Lithium Ion Batteries.
AB  - A porous silicon and carbon composite (PSi/C) with granadilla-like structure as
      an anode material for lithium-ion batteries has been easily fabricated by spray
      drying and subsequent pyrolysis treatments. For the PSi/C, yolk-shell-structured
      Si/C nanobeads are equably distributed inside the porous carbon framework. The
      key point of this work is the combination of the advantages of both the yolk
      shell structure and porous structure in one system. The void space inside the
      yolk-shell Si/C nanobeads and the interconnected three-dimensional porous carbon
      frameworks can effectively enhance the cyclic stability and conductivity of this
      composite. As expected, PSi/C with 15.4% silicon content exhibited a specific
      capacity as high as 1357.43 mAh g-1 and retained 933.62 mAh g-1 beyond 100 cycles
      at 100 mA g-1. Moreover, it showed a reversible specific capacity as high as
      610.38 mAh g-1 at 1000 mA g-1, even after 3000 cycles.

PMID- 30209940
TI  - Wearable Wire-Shaped Symmetric Supercapacitors Based on Activated Carbon-Coated
      Graphite Fibers.
AB  - With the advantages of being lightweight, flexible, and wearable, wire-shaped
      supercapacitors have received tremendous attention in wearable and portable power
      sources in recent years. Considering the demands for large-scale applications, it
      is necessary to explore a facile and convenient preparation approach for wire
      shaped supercapacitors. Herein, we reported a simple approach to fabricate wire
      shaped electrodes by a dipping method, which possessed a nitric acid-activated
      graphite fiber core and an activated carbon-coating layer structure. Parallel and
      symmetric all-solid-state wire-shaped supercapacitors (PWSCs) based on the
      electrodes were fabricated. The as-fabricated PWSC showed high energy density
      (6.60 W h/kg, 8.08 mW h/cm, and 1 mV/s) and power density (253 mW/kg, 0.31 mW/cm,
      and 100 mV/s) and excellent flexibility. Furthermore, this wire-shaped
      supercapacitor may bring broader application prospects for energy storage devices
      in future wearable electronic areas.

PMID- 30209941
TI  - Toward the Detection and Identification of Single Bacteria by Electrochemical
      Collision Technique.
AB  - Fast and cost-efficient detection and identification of bacteria in food and
      water samples and biological fluids is an important challenge in bioanalytical
      chemistry. It was shown recently that bacteria can be detected by measuring the
      decrease in the diffusion current to the ultramicroelectrode caused by cell
      collisions with its surface. To add selectivity to the bacteria detection, herein
      we show the possibility of collision experiments with the signal produced by
      electrochemical activity of bacterial cells reducing (or oxidizing) redox
      species. The mediator oxidation/reduction rate can be used to identify different
      types of bacteria based on their specific redox activities. Here we report the
      analysis of electrochemical collision transients produced by two kinds of
      bacteria, Escherichia coli and Stenotrophomonas maltophilia. The effects of the
      charge and redox activity of bacterial cells on collision events are discussed.
      The current transients due to live cell collisions were compared to those
      produced by bacteria killed either by heavy metal ions (cobalt) or by an
      antibiotic (colistin). This approach is potentially useful for evaluating the
      effectiveness of antimicrobial agents. Finite-element simulations were carried
      out to model collision transients.

PMID- 30209942
TI  - Enhanced Mixing of Microvascular Self-Healing Reagents Using Segmented Gas-Liquid
      Flow.
AB  - Microvascular self-healing systems have previously been demonstrated to restore
      large-scale damage and achieve repeated healing of multiple damage events in
      polymers. However, the healing performance of these systems is often limited
      because the laminar nature of flow in microchannels  results in poor mixing of
      two-part self-healing reagents. In this paper, we introduce segmented gas-liquid
      flow (SGLF) to enhance the mixing of reagents in microvascular self-healing
      systems. In SGLF, discrete liquid slugs containing self-healing reagents are
      separated by gas bubbles while flowing through a single microchannel.
      Recirculating streamlines within the liquid slugs can enhance the mixing of
      miscible liquids such as healing reagents. We investigate the effect of SGLF on
      mixing and healing for a two-stage chemistry used to restore large-scale damage
      in thermoset polymers. Additionally, we employ SGLF to deliver an epoxy-thiol
      chemistry, enabling the repeated recovery of fracture toughness in glass fiber
      reinforced composites. In both systems, the mixing of healing agents delivered by
      SGLF is enhanced compared to alternative microvascular delivery strategies. For
      the two-stage chemistry, SGLF increases the maximum damage size that can be
      healed by 25% compared to laminar single-phase flow. Furthermore, there are
      concomitant increases in the extent of polymerization and the mechanical
      properties of the restored material, including a fivefold increase in the peak
      load sustained during a push-out test. For the epoxy-thiol chemistry, SGLF
      enables multiple healing cycles with healing efficiency above 100%. On the basis
      of these results, we envision that SGLF could improve performance for a variety
      of microvascular self-healing systems with different host materials, damage
      modes, and healing chemistries.

PMID- 30209943
TI  - Computational Insight into the Activation Mechanism of Carcinogenic N'
      Nitrosonornicotine (NNN) Catalyzed by Cytochrome P450.
AB  - Tobacco-specific N'-nitrosonornicotine (NNN), a genotoxic nitrosamine classified
      as Group 1 carcinogen, is also present in atmospheric particulate matter and has
      even been detected as a new disinfection byproduct in wastewaters. NNN generally
      requires metabolic activation by cytochrome P450 enzymes to exert its
      genotoxicity, but the respective biotransformation pathways have not been
      described in detail. In this work, we performed density functional theory (DFT)
      calculations to unravel possible NNN activation pathways including alpha
      hydroxylation, beta-hydroxylation, pyridine N-oxidation, and norcotinine
      formation. The results reveal an initial rate-determining Halpha-atom abstraction
      step for alpha-hydroxylation, followed by an unexpected kinetic competition
      between denitrosation and OH rebound, leading to ( iso-)myosmine as a detoxified
      product and alpha-hydroxyNNNs as the precursor of carcinogenic diazohydroxides,
      respectively. Further detoxification routes are given by beta-hydroxylation with
      relative high reaction barrier and N-oxidation with comparable barrier to the
      toxifying alpha-hydroxylation. Moreover, we show for the first time how
      norcotinine can be generated as a minor NNN metabolite that is formed from iso
      myosmine through a unique porphyrin-assisted H atom 1,2-transfer mechanism. These
      results demonstrate that the carcinogenic potential of NNN is subject to a
      kinetic competition between activating and deactivating metabolic routes, and
      identify respective biomarkers to inform about the individual risk associated
      with NNN exposure.

PMID- 30209944
TI  - Low-Cost Nanostructures from Nanoparticle-Assisted Large-Scale Lithography
      Significantly Enhance Thermal Energy Transport across Solid Interfaces.
AB  - Enhancing thermal energy transport across solid interfaces is of critical
      importance to a wide variety of applications ranging from energy systems and
      lighting devices to electronics. Nanoscale surface roughness is usually
      considered detrimental to interfacial thermal transport because of its role in
      phonon scattering. In this study, however, we demonstrate significant thermal
      conductance enhancements across metal-semiconductor interfaces by as much as 90%
      higher than that of the planar interfaces using engineered nanostructures
      fabricated by Au nanoparticle (NP)-assisted lithography, where self-assembled Au
      NPs are used as an efficient etching mask to pattern solid substrates over large
      surface areas. The enlarged interfacial contact area due to the presence of
      nanostructures is the main reason for the significantly enhanced thermal
      transport. It is further demonstrated that the conductance can be systematically
      tuned over a wide range through the use of the Au NP self-assembly process that
      is regulated by a sacrificial Sb layer whose thickness determines the size and
      density of the nanostructures produced. This strategy is tested on two
      technologically important semiconductors, Si and GaN, and their interfacial
      thermal conductance with Al being measured using the time-domain
      thermoreflectance technique. Moreover, the nanostructured interfaces can maintain
      the enhanced conductance for a temperature range of 30-110  degrees C-the
      operating temperatures commonly experienced by energy, lighting, and electronic
      devices. Our results could provide a wafer-scale and low-cost strategy for
      improving the thermal management of these devices.

PMID- 30209947
TI  - Rhodium-Catalyzed Site-Selective ortho-C-H Activation: Enone Carbonyl Directed
      Hydroarylation of Maleimides.
AB  - Enone carbonyl directed 1,4-addition of ortho-C-H bond in chalcones to maleimides
      was developed under the catalysis of Rh(III). This reaction furnished a variety
      of chalcone-based pharmacologically useful 3-arylated succinimide derivatives in
      good yields with excellent selectivity.

PMID- 30209946
TI  - Medermycin-Type Naphthoquinones from the Marine-Derived Streptomyces sp. XMA39.
AB  - Four new medermycin-type naphthoquinones, strepoxepinmycins A-D (1-4), and one
      known compound, medermycin (5), were identified from Streptomyces sp. XMA39.
      Their structures were elucidated by analysis of HRESIMS, 1D and 2D NMR
      spectroscopic data, and ECD calculations. Among these compounds, strepoxepinmycin
      A (1) represents a rare 5,10-oxepindione ring system typically formed by a Baeyer
      Villiger oxidation, and strepoxepinmycin B (2) is an isolation artifact derived
      from 1. Bioactivity evaluations of these compounds showed that compounds 3 and 4
      exhibited cytotoxicity against HCT-116 and PC-3 cancer cell lines and 4 exhibited
      moderate inhibition of ROCK 2 protein kinase. In addition, all of the new
      compounds showed antibacterial activity against Escherichia coli and methicillin
      resistant Staphylococcus aureus and antifungal activity against Candida albicans.

PMID- 30209945
TI  - Label-Free Proteomic Approach to Characterize Protease-Dependent and -Independent
      Effects of sarA Inactivation on the Staphylococcus aureus Exoproteome.
AB  - The staphylococcal accessory regulator A ( sarA) impacts the extracellular
      accumulation of Staphylococcus aureus virulence factors at the level of
      intracellular production and extracellular protease-mediated degradation. We
      previously used a proteomics approach that measures protein abundance of all
      proteoforms to demonstrate that mutation of sarA results in increased levels of
      extracellular proteases and assesses the impact of this on the accumulation of S.
      aureus exoproteins. Our previous approach was limited as it did not take into
      account that large, stable proteolytic products from a given protein could result
      in false negatives when quantified by total proteoforms. Here, our goal was to
      use an expanded proteomics approach utilizing a dual quantitative method for
      measuring abundance at both the total proteoform and full-length exoprotein
      levels to alleviate these false negatives and thereby provide for
      characterization of protease-dependent and -independent effects of sarA mutation
      on the S. aureus exoproteome. Proteins present in conditioned medium from
      overnight, stationary phase cultures of the USA300 strain LAC, an isogenic sarA
      mutant, and a sarA mutant unable to produce any of the known extracellular
      proteases ( sarA/protease) were resolved using one-dimensional gel
      electrophoresis. Quantitative proteomic comparisons of sarA versus sarA/protease
      mutants identified proteins that were cleaved in a protease-dependent manner
      owing to mutation of sarA, and comparisons of sarA/protease mutant versus the LAC
      parent strain identified proteins in which abundance was altered in a sarA mutant
      in a protease-independent manner. Furthermore, the proteins uniquely identified
      by the full-length data analysis approach eliminated false negatives observed in
      the total proteoform analysis. This expanded approach provided for a more
      comprehensive analysis of the impact of mutating sarA on the S. aureus
      exoproteome.

PMID- 30209948
TI  - PULSE SPR: A High Throughput Method to Evaluate the Domain Stability of
      Antibodies.
AB  - Downstream purification of therapeutic antibodies requires candidates to be
      stable under various stress conditions, such as low pH. Current approaches to
      assess the conformational or colloidal stability of biologics may require
      significant amounts of material, and the testing may occur over an extended
      period of time. Furthermore, typical methodologies for early stability testing
      often do not directly address low pH stability, but focus more on conditions
      suitable for long-term drug product storage. Here we report a high-throughput
      method that measures protonation-induced unfolding of ligand binding sites for
      stability evaluation by surface plasmon resonance or PULSE SPR. This method,
      which requires only several micrograms of sample, is highly sensitive to the
      structural integrity of ligand binding sites and correlates well with thermal and
      chemical conformational stability. Combined with ligands targeting different
      regions of antibodies, this method allows a comprehensive assessment of antibody
      domain stability. By applying PULSE SPR, we found that antibodies with different
      complementarity-determining regions (CDRs), frameworks, formats, and interchain
      disulfide bonds showed different stabilities under acidic conditions.
      Additionally, biologics that aggregated in solution also had poor low pH
      stability. Taken together, PULSE SPR is a high-throughput and low sample
      consumption method that can be adopted to evaluate antibody domain stability and
      aggregation at low pH, which are two important aspects of therapeutic biologics.

PMID- 30209950
TI  - Redox-Dependent Copper Carrier Promotes Cellular Copper Uptake and Oxidative
      Stress-Mediated Apoptosis of Cancer Cells.
AB  - Transportation of exogenous copper ions into cancer cells by copper carriers has
      gained increasing interest for cancer chemotherapy. We disclosed herein a redox
      dependent copper carrier, 2,2'-dithiodipyridine (DPy), which binds copper ions
      and carries the cargo into cells. The cellular reducing environment cleaved the
      disulfide bond in DPy to facilitate unloading copper ions. The elevated copper
      level then elicits oxidative stress and subsequently promotes the reformation of
      DPy. Further mechanistic studies revealed that the DPy/copper combination
      predominantly targets the cellular redox-regulating systems, including the
      thioredoxin system and the glutathione system, to induce the oxidative stress
      mediated death of tumor cells. The discovery of DPy as a cleavable and recyclable
      copper shuttle provides a proof of concept for designing novel biomaterials for
      copper transportation as potential anticancer agents.

PMID- 30209949
TI  - Secondary Carbocations in the Biosynthesis of Pupukeanane Sesquiterpenes.
AB  - The results of quantum chemical calculations on putative biosynthetic carbocation
      cyclization/rearrangements leading to pupukeanane and related sesquiterpenes
      indicate that a secondary carbocation proposed as an intermediate is not a
      minimum on the potential energy surface and instead resides in a region of the
      potential energy surface associated with a plateau containing multiple exit
      channels.

PMID- 30209951
TI  - Benzodithiophene-Dithienylbenzothiadiazole Copolymers for Efficient Polymer Solar
      Cells: Side-Chain Effect on Photovoltaic Performance.
AB  - A new series of low band gap D-A alternating polymers based on 4,5-bis((2
      ethylhexyl)oxy)benzo[2,1- b:3,4- b']dithiophene (BDT) and 5-fluoro-4,7-bis(4
      alkylthien-2-yl)benzo[ c][1,2,5]thiadiazole bearing different size of lateral
      alkyl substituents, namely, PfBB- n, n = 8, 10, 12, 14, and 16, was designed and
      synthesized for high-performance bulk heterojunction (BHJ) polymer solar cells
      (PSCs). PfBB- n-bearing linear alkyl side chains exhibited strong and
      controllable aggregation in both solution and solid states, which gives rise to a
      significant bathochromic shift of the absorption cut-off down to ~780 nm in thin
      film. In addition, the strong and wide absorption (350-800 nm) of PfBB- n
      polymers can compensate for the relatively weak absorption of PC71BM,
      particularly in the 300-400 range nm to enhance light harvesting of such an
      active blend. BHJ solar cells based on PfBB- n:PC71BM blends as an active layer
      showed power conversion efficiency (PCE) in the range 7.8-9.7%. Because of the
      strong stacking interchain interactions, PfBB-12-based PSC exhibited aggregation
      induced spectral broadening, superior structural order, higher exciton
      dissociation, higher and more balanced charge carrier mobilities, as well as
      reduced recombination losses. As a result, PfBB-12-based device afforded the best
      PCE of 9.7%, with the highest short-circuit current density ( Jsc) of 16.6 mA cm
      2 and open-circuit voltage ( Voc) of 0.92 V among devices fabricated. These
      results demonstrate that the alkyl side chain of the polymer significantly
      affects the absorption, morphology, and electronic properties of the active blend
      of PfBB- n/PC71BM, which would provide an alternative useful tool to fine-tune
      the device performance. Our results also highlight that the electron-rich
      benzo[2,1- b:3,4- b']dithiophene building block, BDT, is highly useful for the
      construction of low band gap D-A polymer for highly efficient PSCs.

PMID- 30209952
TI  - Effect of androgen deprivation and radiation therapy on MRI fiber tractography in
      prostate cancer: can we assess treatment response on imaging?
AB  - OBJECTIVE:: To evaluate quantitative changes in Diffusion Tensor Magnetic
      Resonance Tractography in prostate cancer following androgen deprivation and
      radiation therapy. METHODS:: 22 patients with elevated PSA and biopsy proven
      prostate carcinoma who underwent MRI of the prostate at 1.5 T with an endorectal
      coil were included. Group A) was the study group (n = 11), participants who
      underwent androgen deprivation and/or radiation therapy and group B) were Gleason
      matched control group (n = 11) participants who did not undergo such therapy.
      Diffusion weighted images were used to generate three-dimensional (3D) map of
      fiber tracts from DTI. 3D regions of interest (ROI) were drawn over the tumor and
      healthy prostatic parenchyma in both groups to record tract number and tract
      density. Tumor region and normal parenchymal tract densities within each group
      were compared. RESULTS:: Mean tract density in the tumor region and normal
      parenchyma was 2.3 and 3.3 in study group (tract numbers: 116.6 and 170.2
      respectively) and 1.6 and 2.7 in the control group respectively (tract numbers:
      252.5 and 346.3 respectively). The difference between these values was
      statistically significant for the control group (p = 0.0018) but not for the
      study group (p = 0.11). The difference between the tract numbers of tumor and
      normal parenchyma appears to narrow following therapy. CONCLUSION:: The study
      demonstrated utility in using tractography as a biomarker in prostate cancer
      patients post treatment. ADVANCES IN KNOWLEDGE:: Quantitative DTI fiber
      tractography is a promising imaging biomarker to quantitatively assess treatment
      response in the setting of post-androgen deprivation and radiation therapy for
      prostate cancer.

PMID- 30209953
TI  - Bi-plane and single plane angiography: a study to compare contrast usage and
      radiation doses for adult cardiac patients in diagnostic studies.
AB  - OBJECTIVE:: This study compares the performance of bi-plane coronary angiography
      against single plane angiography in terms of the volume of contrast used (ml) and
      the total dose-area product (DAP) (MUGym2) to the patient measured directly via
      flat panel detectors. METHODS:: A total of 5176 adult diagnostic cardiac
      angiograms from a hospital in Brisbane, Australia were retrospectively studied.
      Patients with aortograms, iliac or femoral artery imaging, and stenting or graft
      interventions were excluded. Student's t-tests were used to compare means, and
      confounding variables were compared using multivariate regression. This
      quantified the effects of bi-plane system use holding constant other factors
      (e.g.) body mass index (BMI), age, room, sex, number of digital acquisitions and
      fluoro time. RESULTS:: Bi-plane imaging had an average difference in mean
      contrast use of -15.1 ml [15.5% 95% confidence interval (CI) (-13.2, -17.0)
      p<0.001], multivariate regression demonstrated a -27.0 ml reduction in contrast
      use [28% 95% CI (-29.0, -24.83) p<0.0001] when the significant effects of fluoro
      time, number of digital acquisitions, BMI and sex were held constant. Bi-plane
      imaging had an average difference in mean DAP of + 887.1 MUGym2 [23% 95% CI
      (+1110.7, +663.4) p < 0.001], whilst multivariate regression found a +628.3 Gym2
      increase in DAP [16% 95% CI (+467.5, +789.3) p<0.001] when the significant
      effects of fluoro time, number of digital acquisitions, BMI and sex were held
      constant. CONCLUSION:: These results demonstrate that bi-plane imaging uses less
      contrast media than single-plane imaging for coronary angiography at the expense
      of more radiation. Bi-plane imaging may be preferable in patients with renal
      impairment, however single plane imaging may be preferable in those without renal
      impairment. ADVANCES IN KNOWLEDGE:: This is a large cohort and statistically
      comprehensive study comparing bi-plane and single plane coronary angiography.
      Other studies 4, 5, 6, 12 have used Student's t-tests to measure the difference
      between means, however this provides no causative information on the differences
      found. This study provides a view of the causative impact of bi-plane usage on
      DAP and contrast use via multivariate regression modelling.

PMID- 30209954
TI  - Value of PET/MRI for assessing tumor resectability in NSCLC-intra-individual
      comparison with PET/CT.
AB  - OBJECTIVE:: The purpose of this study was to compare the diagnostic accuracy of
      positron emission tomography (PET)/MRI with PET/CT for determining tumor
      resectability of non-small cell lung cancer (NSCLC). METHODS:: Sequential
      trimodality PET/CT/MRI was performed in 36 patients referred with the clinical
      question of resectability assessment in NSCLC. PET/CT and PET/MR images including
      T1 weighted sequence (T1-Dixon) and respiration gated T2 weighted sequence (T2
      Propeller) were evaluated for resectability-defining factors; i.e. longest
      diameter of the tumor, minimal tumor distance to the carina, mediastinal
      invasion, invasion of the carina, pleural infiltration, pericardial infiltration,
      diaphragm infiltration, presence of additional nodules. RESULTS:: There was no
      significant difference of maximal axial diameter measurements of the primary lung
      tumors and narrow limits of agreement in Bland-Altman analysis ranging from -11.1
      mm to + 11.8  mm for T2-Propeller and from -14.3  mm to + 13.8  mm for T1-Dixon
      sequence. A high agreement of PET/MR with PET/CT for the different resectability
      defining factors was observed (k from 0.769 to 1.000). There was an excellent
      agreement of T2-Propeller sequence and CT for additional pulmonary nodule
      detection (k of 0.829 and 0.833), but only a moderate and good agreement using T1
      Dixon sequence (k of 0.484 and 0.722). CONCLUSION:: In NSCLC the use of PET/MRI,
      including a dedicated pulmonary MR imaging protocol, provides a comparable
      diagnostic value for determination of tumor resectability compared to PET/CT.
      ADVANCES IN KNOWLEDGE:: Our findings suggest that whole body PET/MRI can safely
      be used for the local staging of NSCLC patients. Further studies are warranted to
      determine whether it is feasible to integrate an imaging sequence in a whole body
      PET/MRI setting with the potential advantage of detection of liver or brain
      metastases.

PMID- 30209955
TI  - The use of antiplatelet agents after an acute coronary syndrome in a large
      community Italian setting of more than 12 million subjects.
AB  - BACKGROUND: Antiplatelet agents are the cornerstone of medical treatment in acute
      coronary syndromes. The aim of this study was to evaluate the clinical
      epidemiology of patients after an acute coronary syndrome treated with different
      antiplatelet agent regimens in a large real community setting. METHODS: The ARCO
      database, including more than 12 million inhabitants, was evaluated. Antiplatelet
      agent prescriptions were analysed as follows: aspirin, clopidogrel, other
      antiplatelet agents used alone; the free and fixed combination of clopidogrel and
      aspirin; the free combination of aspirin with other antiplatelet agents.
      Healthcare costs included drug prescriptions (prices reimbursed by the Italian
      National Health System), outpatient specialist services and hospitalisations
      (Italian national tariffs). RESULTS: From 1 January to 31 December 2014, 26,834
      patients were discharged after an acute coronary syndrome. Of these, 19,333 (77%)
      were prescribed with an antiplatelet agent. Among patients undergoing a
      revascularisation procedure either percutaneous or surgical (47% of the total
      population), antiplatelet agents were prescribed in 90% of cases. Dual
      antiplatelet agent therapy was prescribed in 49.6% of the total population and in
      68.5% of those treated invasively. Prescription continuity was observed in just
      75% of patients. The highest adherence was observed for the fixed combination of
      aspirin/clopidogrel (81.5%). Throughout one year of follow-up re-hospitalisation
      occurred in 47.9% of the patients and the direct cost per patient treated with an
      antiplatelet agent was ?13,297 versus ?16,647 in patients not treated with
      antiplatelet agents. CONCLUSIONS: This study highlights that antiplatelet agent
      prescriptions, specifically dual antiplatelet agent therapy, are at least
      suboptimal as well as in prescription continuity. Hospitalisations were frequent
      and were the main driver of the costs, accounting for 84% of the total costs for
      the Italian National Health System.

PMID- 30209956
TI  - Combined application of isotropic Three-Dimensional fast spin echo (3D-FSE-Cube)
      With 2-point Dixon fat/water separation (FLEX) and 3D-FSE-Cube in MR
      Dacryocystography.
AB  - OBJECTIVE: To evaluate the image quality of magnetic resonance dacryocystography
      (MRD) using 3D-FSE-Cube and 3D-FSE-Cube-Flex sequences to examine the lacrimal
      drainage system (LDS). METHOD: Twenty-one healthy volunteers underwent 3D-FSE
      Cube and 3D-FSE-Cube-Flex MRD after topical administration of compound sodium
      chloride eye drops. Two radiologists assessed LDS images in a blinded fashion.
      The signal-to-noise ratio (SNR) of fluid-filling and the contrast-to-noise ratio
      (CNR) of fluid-turbinate were compared between the two sequences. Overall image
      quality, sharpness, artefacts, visualization of anatomical structures, and
      visibility of LDS segments were also compared. RESULT: Overall image quality,
      visualization of anatomic structures, and artefact were significantly better on
      3D-FSE-Cube-Flex MRD (p < 0.001, respectively). when compared to 3D-FSE-Cube. 3D
      FSE-Cube showed lower fluid-filling SNR and fluid-inferior turbinate CNR (all p <
      0.001). In comparison with 3D-FSE-Cube-Flex, 3D-FSE-Cube produced superior
      visibility of the upper drainage segments (superior canaliculi, p = 0.003; common
      canaliculus, p = 0.033; inferior canaliculi, p < 0.001), but inferior in lower
      LDS visibility (lacrimal sac, p = 0.001; nasolacrimal duct, p < 0.001). There was
      no difference in the total number of segments visualized per LDS between the 2
      sequences (p = 0.068). CONCLUSIONS: 3D-FSE-Cube-Flex demonstrated superior image
      quality and visibility of the lower LDS segments. 3D-FSE-Cube showed an advantage
      in visualizing the upper LDS segments. The combination of these sequences can
      improve LDS visibility. Advances in knowledge: 3D-FSE-Cube-Flex provides robust
      water & fat separation and mitigates lower-LDS-associated inhomogeneity
      artefacts. 3D-FSE-Cube shows optimal upper-LDS visualization. The combined
      application of these sequences is a non-invasive and effective method for
      assessing LDS disease.

PMID- 30209957
TI  - Determination of mammographic breast density using a deep convolutional neural
      network.
AB  - OBJECTIVE:: High breast density is a risk factor for breast cancer. The aim of
      this study was to develop a deep convolutional neural network (dCNN) for the
      automatic classification of breast density based on the mammographic appearance
      of the tissue according to the American College of Radiology Breast Imaging
      Reporting and Data System (ACR BI-RADS) Atlas. METHODS:: In this study, 20,578
      mammography single views from 5221 different patients (58.3 +/- 11.5 years) were
      downloaded from the picture archiving and communications system of our
      institution and automatically sorted according to the ACR density (a-d) provided
      by the corresponding radiological reports. A dCNN with 11 convolutional layers
      and 3 fully connected layers was trained and validated on an augmented dataset.
      The model was finally tested on two different datasets against: i) the
      radiological reports and ii) the consensus decision of two human readers. None of
      the test datasets was part of the dataset used for the training and validation of
      the algorithm. RESULTS:: The optimal number of epochs was 91 for medio-lateral
      oblique (MLO) projections and 94 for cranio-caudal projections (CC),
      respectively. Accuracy for MLO projections obtained on the validation dataset was
      90.9% (CC: 90.1%). Tested on the first test dataset of mammographies (850 MLO and
      880 CC), the algorithm showed an accordance with the corresponding radiological
      reports of 71.7% for MLO and of 71.0% for CC. The agreement with the radiological
      reports improved in the differentiation between dense and fatty breast for both
      projections (MLO = 88.6% and CC = 89.9%). In the second test dataset of 200
      mammographies, a good accordance was found between the consensus decision of the
      two readers on both, the MLO-model (92.2%) and the right craniocaudal-model
      (87.4%). In the differentiation between fatty (ACR A/B) and dense breasts (ACR
      C/D), the agreement reached 99% for the MLO and 96% for the CC projections,
      respectively. CONCLUSIONS:: The dCNN allows for accurate classification of breast
      density based on the ACR BI-RADS system. The proposed technique may allow
      accurate, standardized, and observer independent breast density evaluation of
      mammographies. ADVANCES IN KNOWLEDGE:: Standardized classification of
      mammographies by a dCNN could lead to a reduction of falsely classified breast
      densities, thereby allowing for a more accurate breast cancer risk assessment for
      the individual patient and a more reliable decision, whether additional
      ultrasound is recommended.

PMID- 30209958
TI  - Colonic distention and patient acceptance of CT colonography: supine/prone vs
      left/right lateral scanning.
AB  - OBJECTIVE:: To prospectively evaluate and complete the colonic distention and
      patient acceptance of CT colonography (CTC) in the supine/prone and left/right
      lateral positions. METHODS:: A total of 220 consecutive patients were alternately
      allocated to the supine/prone positioning or left/right lateral positioning
      group. Two readers scored the degree of colonic distention by segment using a 4
      point Likert scale (4 = optimal, 3 = adequate, 2 = inadequate, 1 = collapsed). In
      addition, patients were asked to rate the discomfort due to positioning during
      each scan using a 3-point animated face scale (3 = difficult, 2 = somewhat
      unacceptable, 1 = easy). RESULTS:: The overall mean colonic distention scores for
      supine, prone, left lateral, and right lateral positions were 3.16, 3.29, 3.22,
      and 3.42, respectively. Of all, the right lateral position provided the best
      colonic distention (p < 0.01). Combined left lateral and right lateral positions
      provided more adequately distended segments compared with combined supine and
      prone positions (95.6% vs 90.7 %, respectively, p < 0.01). Patient acceptance was
      significantly lower in the prone position compared to other positions; however
      there was no difference in patient acceptance between the supine and left/right
      lateral positions. CONCLUSION:: Right lateral positioning provided the best
      colonic distention and good patient acceptance. ADVANCES IN KNOWLEDGE:: The
      left/right lateral position should be considered for routine CTC positioning
      protocols.

PMID- 30209959
TI  - Dosimetric assessment of tumor control probability in intensity and volumetric
      modulated radiotherapy plans.
AB  - OBJECTIVE:: Radiobiological models have been used to calculate the outcomes of
      treatment plans based on dose-volume relationship. This study examines several
      radiobiological models for the calculation of tumor control probability (TCP) of
      intensity modulated radiotherapy plans for the treatment of lung, prostate, and
      head and neck (H&N) cancers. METHODS:: Dose volume histogram (DVH) data from the
      intensity modulated radiotherapy plans of 36 lung, 26 prostate, and 87  H&N cases
      were evaluated. The Poisson, Niemierko, and Marsden models were used to calculate
      the TCP of each disease group treatment plan. The calculated results were
      analyzed for correlation and discrepancy among the three models, as well as
      different treatment sites under study. RESULTS:: The median value of calculated
      TCP in lung plans was 61.9% (34.1-76.5%), 59.5% (33.5-73.9%) and 32.5% (0.0
      93.9%) with the Poisson, Niemierko, and Marsden models, respectively. The median
      value of calculated TCP in prostate plans was 85.1% (56.4-90.9%), 81.2% (56.1
      88.7%) and 62.5% (28.2-75.9%) with the Poisson, Niemierko, and Marsden models,
      respectively. The median value of calculated TCP in H&N plans was 94.0% (44.0
      97.8%) and 94.3% (0.0-97.8%) with the Poisson and Niemierko models, respectively.
      There were significant differences between the calculated TCPs with the Marsden
      model in comparison with either the Poisson or Niemierko model (p < 0.001) for
      both lung and prostate plans. The TCPs calculated by the Poisson and Niemierko
      models were significantly correlated for all three tumor sites. CONCLUSION::
      There are variations with different radiobiological models. Understanding of the
      correlation and limitation of a TCP model with dosimetric parameters can help
      develop the meaningful objective functions for plan optimization, which would
      lead to the implementation of outcome-based planning. More clinical data are
      needed to refine and consolidate the model for accuracy and robustness. ADVANCES
      IN KNOWLEDGE:: This study has tested three radiobiological models with varied
      disease sites. It is significant to compare different models with the same data
      set for better understanding of their clinical applicability.

PMID- 30209960
TI  - Association between serum level of advanced glycation end products and
      obstructive sleep apnea-hypopnea syndrome: a meta-analysis.
AB  - OBJECTIVE: This meta-analysis was performed to assess the difference in the serum
      level of advanced glycation end products (AGEs) between patients with obstructive
      sleep apnea-hypopnea syndrome (OSAHS) and controls. METHODS: A systematic
      literature search was performed using PubMed, Elsevier, SCI, Wanfang, Weipu, and
      China National Knowledge Internet. Eligible studies that reported the serum AGE
      level in patients with OSAHS were identified by two reviewers. Review Manager
      version 5.2 (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen,
      Denmark) and R version 3.10 ( www.r-project.org ) were employed for data
      synthesis. RESULTS: Five studies involving 670 subjects were identified. The meta
      analysis showed that the mean serum AGE level in the OSAHS group was 0.98 mmol/L
      higher than those in the control group (95% confidence interval, 0.69-1.27).
      CONCLUSIONS: This meta-analysis showed that the serum AGE level was elevated in
      patients with OSAHS. This finding suggests that AGEs may play an important role
      in insulin resistance in OSAHS and serve as a biomarker for patients with OSAHS
      with a high risk of type 2 diabetes mellitus.

PMID- 30209961
TI  - Using Qualitative Inquiry to Enhance a Child Neurology Residency.
AB  - The goal of medical residency programs is to provide educational opportunities to
      residents to facilitate their transformation into independent and competent
      health care practitioners. Despite an abundance of quantitative data on resident
      performance, qualitative data are lacking in published literature. Our study
      involved a standardized interview with all graduating child neurology residents
      to better understand their educational experiences during training. Qualitative
      data analysis resulted in 5 basic themes experienced by all trainees: (1)
      appreciation for faculty supportiveness, (2) appreciation for faculty
      receptiveness to feedback, (3) the difficulty of balancing clinical and academic
      demands during residency, (4) the benefit of structured mentorship and research,
      and (5) the value of independent and experiential learning. Our findings
      demonstrate that qualitative inquiry can be used to better understand the
      educational experience of child neurology residents. The themes identified
      through this qualitative analysis were useful targets for programmatic quality
      improvements.

PMID- 30209962
TI  - Influence of dexmedetomidine and lidocaine on perioperative opioid consumption in
      laparoscopic intestine resection: a randomized controlled clinical trial.
AB  - : Objective The consumption of opioid analgesics could be reduced by the use of
      analgesics with different mechanisms of action. We investigated whether
      additional treatment with dexmedetomidine or lidocaine could reduce opioid
      consumption. Methods We randomized 59 study participants into three groups and
      examined: (i) fentanyl consumption, (ii) consumption of piritramide, and (iii)
      cognitive function and neuropathic pain. The control group received continuous
      propofol infusion and fentanyl boluses. Continuous intravenous infusion of
      dexmedetomidine (0.5 ug/kg/h) was administered to the dexmedetomidine group and
      lidocaine (1.5 mg/kg/h) was administered to the lidocaine group. Results No
      reduction in fentanyl consumption was observed among the groups. However, we
      noted a significantly lower consumption of piritramide on the first and second
      postoperative day in the lidocaine group. Total consumption of piritramide was
      significantly lower in the lidocaine group compared with the control group.
      Conclusions Lidocaine and dexmedetomidine reduced intraoperative propofol
      consumption, while lidocaine reduced postoperative piritramide consumption.
      CLINICAL TRIAL REGISTRATION: NCT02616523.

PMID- 30209963
TI  - Risk factors associated with neonatal thrombocytopenia in pregnant women with
      immune thrombocytopenic purpura.
AB  - OBJECTIVES: To characterize the risk factors associated with neonatal
      thrombocytopenia among pregnant women with immune thrombocytopenic purpura (ITP).
      METHODS: We reviewed the records of ITP patients who delivered during 2006-2016
      at our medical center. RESULTS: Of 253 pregnancies, median maternal age at
      diagnosis was 29 [25-33] years, 222 (87.7%) had previously-diagnosed ITP and 31
      (12.3%) were diagnosed with new-onset ITP during pregnancy. Baseline
      characteristics were comparable between the groups except for a higher proportion
      of nulliparity among those with new-onset disease (p = .002). Maternal nadir
      platelet count was significantly lower among those with new-onset compared to
      previously diagnosed ITP (median 62 * 109/L versus 81 * 109/L, p = .005).
      Neonatal thrombocytopenia (<150 * 109/L) was encountered in 24 (9.5%) pregnancies
      and required treatment in 12 (50%) of them. Neonatal platelet count was directly
      correlated with maternal platelet count at delivery (r = 0.23, p = .01), with
      significantly lower maternal platelet count among those whose newborns
      experienced thrombocytopenia (p < .001). Neonatal thrombocytopenia followed a
      higher proportion of pregnancies of women with new-onset than previously
      diagnosed ITP (22.6 versus 7.7%, p = .02). In multivariate analysis, the presence
      of new-onset ITP (odds ratio [95% CI]: 4.88 (1.68, 14.16), p = .004) was the only
      independent predictor of the development of neonatal thrombocytopenia.
      CONCLUSION: Neonatal thrombocytopenia presented following almost one-tenth of
      pregnancies with ITP. New pregnancy-onset disease was the only prognostic marker
      for neonatal thrombocytopenia. This finding could contribute to risk
      stratification and individualized patient management.

PMID- 30209964
TI  - Comparison between a novel knotless technique and the conventional single knot
      technique of laparoscopic radical prostatectomy by novice laparoscopists.
AB  - OBJECTIVES: This study aimed to investigate a novel knotless technique for novice
      laparoscopists in traditional laparoscopic radical prostatectomy. METHODS: We
      studied 68 patients who had a novel technique performed in laparoscopic radical
      prostatectomy (knotless group) and 89 who had the conventional single knot
      technique (single knot group). The operations were all performed by novice
      laparoscopists with experience of fewer than 100 cases of laparoscopic radical
      prostatectomy. Knotless suture of the dorsal vein complex was conducted using a
      barbed self-retaining suture with three bites at the same location. The knotless
      urethrovesical anastomosis technique was conducted using a unidirectional single
      running fashion with a barbed self-retaining suture. RESULTS: There were no
      significant differences in the estimated blood loss, complication rate,
      postoperative hospital stay, anastomotic leakage rate, continence at 6 months
      after surgery, and positive margin rate between the two groups. The mean
      anastomotic time (24.9 vs. 44.2 min), operative time (168.1 vs. 201.8 min), and
      duration of catheter placement (12.8 vs. 19.8 days) were shorter in the knotless
      group than in the single-knot group. CONCLUSIONS: The knotless technique of
      laparoscopic radical prostatectomy is a safe and effective procedure.

PMID- 30209966
TI  - Future Oncology: a 10-year anniversary issue.

PMID- 30209968
TI  - The Protective Effect of Kinship Involvement on the Adjustment of Youth in Foster
      Care.
AB  - Child maltreatment and family dysfunction (e.g., conflict) can have a long-term
      deleterious impact on youth well-being. Using a child welfare sample, this study
      examined whether dysfunction in the nuclear family of origin was associated with
      adjustment problems, including internalizing and externalizing behavior problems,
      beyond the effect of child maltreatment, and whether extended family (kinship)
      involvement protected against youth's adjustment problems. Participants included
      171 children and adolescents (mean age = 10.15; 50.3% female) who entered foster
      care due to child maltreatment. Results indicated that greater dysfunction in the
      nuclear family of origin and child maltreatment were independently associated
      with greater internalizing and externalizing behavior problems. Results also
      showed that kinship involvement was protective against externalizing behavior
      problems. Moreover, kinship involvement buffered the association between
      dysfunction in family of origin and internalizing behaviors only at low levels of
      family dysfunction. These results support policies that encourage the involvement
      of extended and noncustodial family members in the lives of maltreated youth
      following their entry into foster care.

PMID- 30209965
TI  - Safety and tolerability of sauna detoxification for the protracted withdrawal
      symptoms of substance abuse.
AB  - OBJECTIVE: Protracted drug withdrawal symptoms can last months or years after
      drug cessation, often precipitating a return to substance misuse. We evaluated
      the safety and preliminary health benefits of a unique chemical exposure regimen
      based on exercise, sauna and therapeutic nutrients. METHODS: This was a
      prospective evaluation of 109 individuals sequentially enrolled into a sauna
      detoxification component of a multi-modal, long-term residential substance abuse
      treatment centre. RESULTS: Data from medical charts, client self-reports and
      Short Form Health Survey (SF-36) responses indicated that the Hubbard sauna
      detoxification method was well tolerated, with a 99% completion rate, including
      one human immunodeficiency virus and nine hepatitis C positive clients. There
      were no cases of dehydration, overhydration or heat illness. Statistically
      significant improvements were seen in both mental and physical SF-36 scores at
      regimen completion, as well as in Addiction Severity Index and Global Appraisal
      of Individual Needs Short Screener change scores at rehabilitation program
      discharge, compared with enrolment. CONCLUSIONS: The regimen lacked serious
      adverse events, had a very low discontinuation rate and high client-reported
      satisfaction. The SF-36 data indicated improved physical and emotional symptoms.
      Therefore, broader investigation of this sauna-based treatment regimen is
      warranted.

PMID- 30209969
TI  - How Enclosure and Spatial Organization Affect Residents' Use and Experience of a
      Dementia Special Care Unit: A Case Study.
AB  - AIM: We aim to gain insight into how a dementia special care unit is used and
      experienced by its residents and what design aspects are important therein.
      BACKGROUND: In Flanders, housing for people with dementia evolves toward small
      scale, homelike environments. As population aging challenges the affordability of
      this evolution, architects and other designers are asked to design dementia
      special care units that offer the advantages of small scaleness within the
      context of large-scale residential care facilities. How these units are used and
      experienced is not systematically evaluated. METHOD: A case study was conducted
      in a recently built residential care facility where a dementia special care unit
      was foreseen on the ground floor, yet after a few months was moved to the top
      floor. The case study combined architectural analysis, participant observation,
      and qualitative interviews with residents and care staff. RESULTS: Comparing the
      original situation on the ground floor with the new situation on the top floor
      highlights how enclosure (physical and visual access to outside and the rest of
      the facility) and spatial organization affect how residents use and experience a
      dementia special care unit. CONCLUSIONS: Depending on the type and stage of
      dementia, residents may have different needs for space to move, sensory stimuli,
      and social contact. In order to meet these different needs, confining residents
      to a dementia special care unit to the top floor should be avoided unless it is
      carefully designed, providing sufficient freedom of movement and connection with
      the outside world.

PMID- 30209970
TI  - Dislocation of large-diameter head metal-on-metal total hip arthroplasty and hip
      resurfacing arthroplasty.
AB  - INTRODUCTION: Dislocation of large-diameter head (LDH) metal-on-metal (MoM) total
      hip arthroplasty (THA) or hip resurfacing arthroplasty (HRA) is a rare
      complication. This study aimed to determine the incidence and risk factors for
      dislocation of LDH MoM THAs and HRAs. METHODS: This retrospective analysis
      considered 4038 cementless LDH MoM THAs and HRAs, 3207 THAs in 2912 patients and
      831 HRAs in 757 patients. The end of follow-up was revision due to dislocation.
      Incidence of dislocation was evaluated from this study population of 4038, and
      study groups were formed. The study was designed as a case-control study, and a
      threefold stratified randomised control group was formed. Demographic data were
      collected and radiological analyses were performed in the study groups. RESULTS:
      There were 26/3207 (0.8%) early dislocations in the THA group, and 6/831 (0.7%)
      in the HRA group ( p = 0.9). Most LDH THA dislocations occurred in a group with
      head size ? 38 mm (18/26) ( p < 0.001). In dislocated hips, there were more
      dysplastic acetabula and post-traumatic hips than in the control group ( p =
      0.036). In the dislocation group, the mean acetabulum component anteversion angle
      was 19.6 degrees  (standard deviation [SD] 13.4 degrees ) and in the control
      group it was 23.2 degrees  (SD 10.4 degrees ) ( p = 0.006); 7/32 (21.8%) of
      dislocated THAs needed revision surgery, and mean time to revision from the index
      surgery was 1.2 (SD 2.6) years. DISCUSSION: Dislocations occurred more often in
      THAs of head size ? 38 mm and with a smaller anteversion angle of the acetabulum
      component. Hip dysplasia and post-traumatic osteoarthritis were more common in
      patients with dislocation.

PMID- 30209971
TI  - The 'missing millions': Where do we find them?

PMID- 30209973
TI  - Enhancing diversity to reduce health information disparities and build an
      evidence base for genomic medicine.
AB  - Advances in genomic medicine are arising from efforts to build a national
      learning healthcare system (LHS) and large-scale precision medicine studies.
      However, the underlying evidence base lacks sufficient data from populations
      historically underrepresented in biomedical research. Although the literature on
      health and healthcare disparities is extensive, disparities in the availability
      and quality of health information about diverse and underrepresented populations
      are less well characterized. This Perspective describes scientific and ethical
      benefits to incorporating health information from diverse and underrepresented
      populations in the LHS, resulting in a more robust and generalizable LHS. Near
      term recommendations for incorporating diversity into the evidence base for
      genomic medicine are proposed, even as the groundwork for national and
      international efforts is underway.

PMID- 30209974
TI  - Generation of bioactive nano-composite scaffold of nanobioglass/silk
      fibroin/carboxymethyl cellulose for bone tissue engineering.
AB  - The development of bone tissue construct through tissue engineering approach
      offers a great promise in meeting the increasing demand for repair and
      regeneration of damaged and/or diseased bone tissue. For the generation of bone
      tissue engineered construct, polymer-ceramic composite matrices with
      nanostructure architecture and mesenchymal stem cells (hMSCs) of human origin are
      of prime requirement. Keeping these in view, in the present work a novel
      electrospun nanofibrous silk fibroin (SF)/carboxymethyl cellulose (CMC)/nano
      bioglass (nBG) composite scaffold that mimics native bone extracellular matrix
      with appropriate composition was designed and fabricated by free liquid surface
      electrospinning technique. The scaffold possesses desired morphological,
      structural, biodegradability, bioactivity, surface roughness and mechanical
      properties thereby exhibited an excellent platform to support the growth of
      cells. The in-vitro culture of hMSCs over the developed scaffold has shown
      adhesion, proliferation and viability of cells, thus facilitated cell-scaffold
      construct generation and further extracellular bone matrix formation through
      osteogenic differentiation as evident from alkaline phosphatase activity,
      biomineralization, immunostaining and Runx2/osteocalcin expression assessment.
      Thus, the developed hMSCs seeded scaffold construct might be suitable for bone
      tissue engineering applications.

PMID- 30209972
TI  - Multimorbidity, frailty and chronic obstructive pulmonary disease: Are the
      challenges for pulmonary rehabilitation in the name?
AB  - The overwhelming majority of people with chronic obstructive pulmonary disease
      (COPD) have at least one coexisting medical condition often conceptualized as
      'comorbidities'. These coexisting conditions vary in severity and impact; it is
      likely that for some patients, COPD is not their most important or severe
      condition. The concepts of multimorbidity and frailty may be useful to understand
      the broader needs of people with COPD undergoing pulmonary rehabilitation.
      Multimorbidity describes the coexistence of two or more chronic conditions,
      without reference to a primary condition. Best care for people with
      multimorbidity has been described as a shift from providing disease-focused to
      patient-centred care. Pulmonary rehabilitation is well placed to deliver such
      care as it focuses on optimizing function, encourages integration across care
      settings, values input from multidisciplinary teams and measures patient
      important outcomes. When designing optimal pulmonary rehabilitation services for
      people with multimorbidity, the concept of frailty may be useful. Frailty focuses
      on impairments rather than medical conditions including impairments in mobility,
      strength, balance, cognition, nutrition, endurance, mood and physical activity.
      Emerging data suggest that frailty may be modifiable with pulmonary
      rehabilitation. The challenge for pulmonary rehabilitation clinicians is to
      broaden our perspective on the role and outcomes of pulmonary rehabilitation for
      people with multimorbidity.

PMID- 30209975
TI  - Thyroid hormone (T3) stimulates brown adipose tissue activation via mitochondrial
      biogenesis and MTOR-mediated mitophagy.
AB  - The thyroid hormone triiodothyronine (T3) activates thermogenesis by uncoupling
      electron transport from ATP synthesis in brown adipose tissue (BAT) mitochondria.
      Although T3 can induce thermogenesis by sympathetic innervation, little is known
      about its cell autonomous effects on BAT mitochondria. We thus examined effects
      of T3 on mitochondrial activity, autophagy, and metabolism in primary brown
      adipocytes and BAT and found that T3 increased fatty acid oxidation and
      mitochondrial respiration as well as autophagic flux, mitophagy, and
      mitochondrial biogenesis. Interestingly, there was no significant induction of
      intracellular reactive oxygen species (ROS) despite high mitochondrial
      respiration and UCP1 induction by T3. However, when cells were treated with Atg5
      siRNA to block autophagy, induction of mitochondrial respiration by T3 decreased,
      and was accompanied by ROS accumulation, demonstrating a critical role for
      autophagic mitochondrial turnover. We next generated an Atg5 conditional knockout
      mouse model (Atg5 cKO) by injecting Ucp1 promoter-driven Cre-expressing
      adenovirus into Atg5Flox/Flox mice to examine effects of BAT-specific autophagy
      on thermogenesis in vivo. Hyperthyroid Atg5 cKO mice exhibited lower body
      temperature than hyperthyroid or euthyroid control mice. Metabolomic analysis
      showed that T3 increased short and long chain acylcarnitines in BAT, consistent
      with increased beta-oxidation. T3 also decreased amino acid levels, and in
      conjunction with SIRT1 activation, decreased MTOR activity to stimulate
      autophagy. In summary, T3 has direct effects on mitochondrial autophagy,
      activity, and turnover in BAT that are essential for thermogenesis. Stimulation
      of BAT activity by thyroid hormone or its analogs may represent a potential
      therapeutic strategy for obesity and metabolic diseases. Abbreviations: ACACA:
      acetyl-Coenzyme A carboxylase alpha; AMPK: AMP-activated protein kinase; Acsl1:
      acyl-CoA synthetase long-chain family member 1; ATG5: autophagy related 5; ATG7:
      autophagy related 7; ATP: adenosine triphosphate; BAT: brown adipose tissue; cKO:
      conditional knockout; COX4I1: cytochrome c oxidase subunit 4I1; Cpt1b: carnitine
      palmitoyltransferase 1b, muscle; CQ: chloroquine; DAPI: 4',6-diamidino-2
      phenylindole; DIO2: deiodinase, iodothyronine, type 2; DMEM: Dulbecco's modified
      Eagle's medium; EIF4EBP1: eukaryotic translation initiation factor 4E binding
      protein 1; Fabp4: fatty acid binding protein 4, adipocyte; FBS: fetal bovine
      serum; FCCP: carbonyl cyanide-4-(trifluoromethoxy)phenylhydrazone; FGF:
      fibroblast growth factor; FOXO1: forkhead box O1; GAPDH: glyceraldehyde-3
      phosphate dehydrogenase; GFP: green fluorescent protein; Gpx1: glutathione
      peroxidase 1; Lipe: lipase, hormone sensitive; MAP1LC3B: microtubule-associated
      protein 1 light chain 3; mRNA: messenger RNA; MTORC1: mechanistic target of
      rapamycin kinase complex 1; NAD: nicotinamide adenine dinucleotide; Nrf1: nuclear
      respiratory factor 1; OCR: oxygen consumption rate; PBS: phosphate-buffered
      saline; PCR: polymerase chain reaction; PPARGC1A: peroxisome proliferative
      activated receptor, gamma, coactivator 1 alpha; Pnpla2: patatin-like
      phospholipase domain containing 2; Prdm16: PR domain containing 16; PRKA: protein
      kinase, AMP-activated; RPS6KB: ribosomal protein S6 kinase; RFP: red fluorescent
      protein; ROS: reactive oxygen species; SD: standard deviation; SEM: standard
      error of the mean; siRNA: small interfering RNA; SIRT1: sirtuin 1; Sod1:
      superoxide dismutase 1, soluble; Sod2: superoxide dismutase 2, mitochondrial;
      SQSTM1: sequestosome 1; T3: 3,5,3'-triiodothyronine; TFEB: transcription factor
      EB; TOMM20: translocase of outer mitochondrial membrane 20; UCP1: uncoupling
      protein 1 (mitochondrial, proton carrier); ULK1: unc-51 like kinase 1; VDAC1:
      voltage-dependent anion channel 1; WAT: white adipose tissue.

PMID- 30209978
TI  - "A randomized clinical trial of radiation therapy versus thermoradiotherapy in
      stage IIIB cervical carcinoma" of Yoko Harima et al. (2001): multiple biases and
      no advantage of hyperthermia.

PMID- 30209979
TI  - "A randomised clinical trial of radiation therapy versus thermoradiotherapy in
      stage IIIB cervical carcinoma" of Yoko Harima et al. (2001): a response letter to
      the editor of comments from Dr. Roussakow.

PMID- 30209976
TI  - PTPN14 regulates Roquin2 stability by tyrosine dephosphorylation.
AB  - Protein phosphorylation regulates a variety of cellular signaling pathways and
      fundamental mechanisms in cells. In this paper, we demonstrate that the mRNA
      decay factor Roquin2 is phosphorylated at tyrosine residue in position 691 in
      vivo. This phosphorylation disrupts the interaction with KLHL6, the E3 ligase for
      Roquin2. Furthermore, we establish that the tyrosine phosphatase PTPN14
      specifically interacts with Roquin2 through its phosphatase domain and
      dephosphorylates Roquin2 tyrosine 691. Overexpression of PTPN14 promotes Roquin2
      degradation in a KLHL6-dependant manner by promoting interaction with KLHL6.
      Collectively, our findings reveal that PTPN14 negatively regulates the protein
      stability of Roquin2, thereby adding a new layer of regulation to the KLHL6
      Roquin2 axis.

PMID- 30209977
TI  - Quantitative assessment of knee extensor thrust, flexed-knee gait, insufficient
      knee flexion during the swing phase, and medial whip in hemiplegia using three
      dimensional treadmill gait analysis.
AB  - BACKGROUND: Most people with hemiplegia experience gait changes after a stroke.
      Abnormal gait patterns in stroke patients vary across subjects and this make it
      difficult to assess the cause of gait abnormalities. Therefore, it is necessary
      to quantitatively evaluate abnormal gait patterns through gait analysis for
      stroke patients. OBJECTIVE: To develop and evaluate the validity of quantitative
      assessments of the degree of knee extensor thrust, flexed-knee gait, insufficient
      knee flexion during the swing phase, and medial whip. METHODS: Forty-six healthy
      control subjects and 112 people with hemiplegia participated. From the 112
      patients, 50 patients were selected into each abnormal gait pattern (knee
      extensor thrust, flexed-knee gait, insufficient knee flexion during the swing
      phase, and medial whip) with some overlap. Participants were instructed to walk
      on a treadmill and were recorded using a three-dimensional motion analysis
      system. An index to quantify each of the four abnormal gait patterns exhibited by
      the patients was calculated from the three-dimensional coordinate data. The
      indices were developed based on the definition of the abnormal gait patterns. The
      index values for the patients were compared with those of healthy subjects as
      well as with the results of observational gait assessment by three physical
      therapists with expertise in gait analysis. RESULTS: Strong correlation was
      observed between the index value and the median observational rating for all four
      abnormal gait patterns (-0.64 to -0.86). Most of the patients with an abnormal
      gait pattern had a higher index value than the healthy subjects. CONCLUSIONS: The
      use of these indices in gait analysis of people with hemiplegia can help to
      diagnose severity of gait disorder, determine the appropriate treatment, and
      evaluate the effectiveness of the treatment.

PMID- 30209981
TI  - Darkening with UVRAG.
AB  - Ultraviolet radiation (UVR)-induced skin pigmentation, afforded by the dark
      organelles termed melanosomes, accounts for the first-line protection against
      environmental UVR that increases the risk of developing skin cancers including
      melanoma. We have recently discovered that UVRAG, originally identified as a
      BECN1-binding macroautophagy/autophagy protein, appears to have a specialized
      function in melanosome biogenesis beyond autophagy through its interaction with
      the biogenesis of lysosome-related organelles complex 1 (BLOC-1). This
      melanogenic function of UVRAG is controlled by the melanocyte-specific
      transcription factor MITF as a downstream effector of the alpha-melanocyte
      stimulating hormone (alpha-MSH)-cAMP signaling in the suntan response, which is
      compromised in BRAF mutant melanoma. Thus we propose a new mode of UVRAG activity
      and regulation in melanocyte biology that may affect melanoma predisposition.

PMID- 30209980
TI  - Effect of single-nucleotide polymorphisms in TRPV1 on burning pain and capsaicin
      sensitivity in Japanese adults.
AB  - Transient receptor potential vanilloid 1 (TRPV1) is a nonselective cation channel
      that is expressed in the sensory neurons and responds to various noxious stimuli
      including heat and capsaicin. The molecular properties of TRPV1 have been clearly
      examined; however, there are obvious individual differences in human sensitivity
      to thermal stimuli and capsaicin. Here, we examined the possibility that
      different genome sequence of human TRPV1 caused the different sensitivity to heat
      or capsaicin. The sensitivities to burning pain and capsaicin of Japanese adult
      subjects were compared with their TRPV1 genome sequence, and we detected 6 single
      nucleotide polymorphisms and 11 single-nucleotide polymorphisms related to
      burning pain and capsaicin sensitivity, respectively. In particular, homozygous
      I585V, a single-nucleotide polymorphism with amino acid substitution,
      significantly related to higher capsaicin sensitivity.

PMID- 30209983
TI  - Adequacy of Pain Control in Patients With Advanced Cancer in Pakistan.
AB  - PURPOSE: Pain is highly prevalent in advanced cancer and requires aggressive
      management. However, pain management in cancer is minimally investigated in
      Pakistan. This cross-sectional study explores the adequacy of pain management in
      patients with advanced stage cancer in Pakistan. METHOD: From January 2017 to May
      2017, a cross-sectional study was conducted at Mayo Hospital, Lahore, Pakistan. A
      total of 218 patients with cancers were interviewed, and 136 patients with pain
      >=5 on a Numerical Rating Scale for pain were included in the study. Demographic
      of patients and clinical characteristics of tumors were also evaluated. RESULTS:
      Only about one-third of the patients with advanced cancer reported adequate pain
      management. Chi-square test, chi2 (1, n = 136) = 33.038, P < .05, indicated that
      pain scores were inversely associated with pain control; inadequate pain control
      was observed in patients with higher pain score and vice versa. Of the 55.88% of
      patients who were prescribed morphine, only 6 patients were compliant with
      treatment recommendations. Most patients were prescribed nonopioid medications
      and tramadol and codeine, which are weak opioid medications. CONCLUSION: The rate
      of undertreatment of cancer pain in Pakistan is alarming. Inadequate clinicians'
      training, patients' and caregivers' beliefs, lack of availability of opioid
      medications, and socioeconomic factors are some of the barriers to effective pain
      control. A multidisciplinary team approach is necessary to follow the World
      Health Organization pain ladder guidelines for the treatment of cancer pain.

PMID- 30209984
TI  - Depression in Registered Nurses: A State of the Science.

PMID- 30209986
TI  - Shoulder Pain Assessment for the Occupational Health Nurse.
AB  - Shoulder pain is a common complaint in the workplace. A shoulder condition may
      arise from acute trauma or non-traumatic work-related activities. Shoulder pain
      falls into three categories: acute, chronic, and referred pain. The occupational
      health nurse can document detailed health histories and focused complaint-driven
      physical examinations. Nurses' expert assessments can guide injured workers to
      necessary treatment, case management, and return to full employment.

PMID- 30209985
TI  - Workplace Romance Can Be Sexual Harassment: Time to Mandate Preventive and
      Protective Sensitivity Training.
AB  - Sensitivity training for workplace romance (WPR) and sexual harassment (SHM)
      across workplaces should be mandated because this knowledge may protect employees
      and employers by preventing workplace romanticism-sexism.

PMID- 30209987
TI  - Depression in Registered Nurses: A State of the Science.
AB  - Registered nurses suffer from depression at almost twice the rate of individuals
      in other professions. Major depression affects both employees and organizations.
      Depression is linked to increases in work absenteeism, short-term disability, and
      decreased productivity and presenteeism. Depression experienced by registered
      nurses may not be fully preventable, but realizing its presence and prevalence in
      the workplace is of vital importance. It is essential that we have a healthy,
      vibrant, and present registered nurse workforce to ensure that quality patient
      outcomes are achieved. This review of 36 articles assesses the current state of
      the science related to depression in registered nurses so that occupational
      health nurses can create pathways and work environments for better mental health
      for registered nurses.

PMID- 30209982
TI  - Fear extinction learning ability predicts neuropathic pain behaviors and amygdala
      activity in male rats.
AB  - Background The amygdala plays a key role in fear learning and extinction and has
      emerged as an important node of emotional-affective aspects of pain and pain
      modulation. Impaired fear extinction learning, which involves prefrontal cortical
      control of amygdala processing, has been linked to neuropsychiatric disorders.
      Here, we tested the hypothesis that fear extinction learning ability can predict
      the magnitude of neuropathic pain. Results We correlated fear extinction learning
      in naive adult male rats with sensory and affective behavioral outcome measures
      (mechanical thresholds, vocalizations, and anxiety- and depression-like
      behaviors) before and after the induction of the spinal nerve ligation model of
      neuropathic pain compared to sham controls. Auditory fear conditioning,
      extinction learning, and extinction retention tests were conducted after baseline
      testing. All rats showed increased freezing responses after fear conditioning.
      During extinction training, the majority (75%) of rats showed a decline in
      freezing level to 50% in 5 min (fear extinction+), whereas 25% of the rats
      maintained a high freezing level (>50%, fear extinction-). Fear extinction- rats
      showed decreased open-arm preference in the elevated plus maze, reflecting
      anxiety-like behavior, but there were no significant differences in sensory
      thresholds, vocalizations, or depression-like behavior (forced swim test) between
      fear extinction+ and fear extinction- types. In the neuropathic pain model (four
      weeks after spinal nerve ligation), fear extinction- rats showed a greater
      increase in vocalizations and anxiety-like behavior than fear extinction+ rats.
      Fear extinction- rats, but not fear extinction+ rats, also developed depression
      like behavior. Extracellular single unit recordings of amygdala (central nucleus)
      neurons in behaviorally tested rats (anesthetized with isoflurane) found greater
      increases in background activity, bursting, and evoked activity in fear
      extinction- rats than fear extinction+ rats in the spinal nerve ligation model
      compared to sham controls. Conclusion The data may suggest that fear extinction
      learning ability predicts the magnitude of neuropathic pain-related affective
      rather than sensory behaviors, which correlates with differences in amygdala
      activity changes.

PMID- 30209989
TI  - Clinical prediction of thrombectomy eligibility: A systematic review and 4-item
      decision tree.
AB  - Background A clinical large anterior vessel occlusion (LAVO)-prediction scale
      could reduce treatment delays by allocating intra-arterial thrombectomy (IAT)
      eligible patients directly to a comprehensive stroke center. Aim To subtract,
      validate and compare existing LAVO-prediction scales, and develop a
      straightforward decision support tool to assess IAT-eligibility. Methods We
      performed a systematic literature search to identify LAVO-prediction scales.
      Performance was compared in a prospective, multicenter validation cohort of the
      Dutch acute Stroke study (DUST) by calculating area under the receiver operating
      curves (AUROC). With group lasso regression analysis, we constructed a prediction
      model, incorporating patient characteristics next to National Institutes of
      Health Stroke Scale (NIHSS) items. Finally, we developed a decision tree
      algorithm based on dichotomized NIHSS items. Results We identified seven LAVO
      prediction scales. From DUST, 1316 patients (35.8% LAVO-rate) from 14 centers
      were available for validation. FAST-ED and RACE had the highest AUROC (both
      >0.81, p < 0.01 for comparison with other scales). Group lasso analysis revealed
      a LAVO-prediction model containing seven NIHSS items (AUROC 0.84). With the GACE
      (Gaze, facial Asymmetry, level of Consciousness, Extinction/inattention) decision
      tree, LAVO is predicted (AUROC 0.76) for 61% of patients with assessment of only
      two dichotomized NIHSS items, and for all patients with four items. Conclusion
      External validation of seven LAVO-prediction scales showed AUROCs between 0.75
      and 0.83. Most scales, however, appear too complex for Emergency Medical Services
      use with prehospital validation generally lacking. GACE is the first LAVO
      prediction scale using a simple decision tree as such increasing feasibility,
      while maintaining high accuracy. Prehospital prospective validation is planned.

PMID- 30209990
TI  - Elevation of cerebrospinal fluid cytokine/chemokines involved in innate, T cell,
      and granulocyte inflammation in pediatric focal cerebral arteriopathy.
AB  - Aim To determine the role of inflammation in pediatric transient focal cerebral
      arteriopathy using cerebrospinal fluid cytokine/chemokines as biomarkers. Methods
      We measured 32 cytokine/chemokines in acute cerebrospinal fluid collected from
      children with stroke due to focal cerebral arteriopathy (n = 5) using multiplex
      immunoassay and compared with two patients with arterial ischemic stroke due to
      other causes (non-focal cerebral arteriopathy group, vertebral dissection, n = 1;
      cryptogenic, n = 1), pediatric encephalitis (n = 43), and non-inflammatory
      neurological disease controls (n = 20). Results Median age in the focal cerebral
      arteriopathy group was 9.3 years (range, 2.8-13 years). In the focal cerebral
      arteriopathy group (n = 5), four patients had middle cerebral +/- distal carotid
      arteriopathy; one patient had posterior circulation arteriopathy. The median time
      from symptom onset to cerebrospinal fluid sampling was four days (range, 0.6-7
      days). Only IL-6, IL-8, CXCL1, and CXCL10 levels were significantly higher in the
      acute cerebrospinal fluid of focal cerebral arteriopathy patients compared to non
      inflammatory neurological disease controls and non-focal cerebral arteriopathy
      stroke. In contrast to focal cerebral arteriopathy, a broad array of Th1, Th2,
      Treg, Th17, B-cell related, and other broad spectrum cytokine/chemokines were
      elevated in encephalitis. Conclusion The elevated cerebrospinal fluid
      cytokine/chemokines support innate, T cell, and granulocyte inflammatory
      mechanisms in children with focal cerebral arteriopathy. This warrants larger
      cohort studies to discriminate primary inflammatory signals of the arteriopathy
      from secondary inflammation due to the stroke itself.

PMID- 30209991
TI  - Use of mobile applications in post-stroke rehabilitation: a systematic review.
AB  - OBJECTIVE: Information technology and mobile devices are potentially beneficial
      and useful in the management of patients who have had stroke, including
      recognition, translation, assessment, and rehabilitation. The objective of this
      study was to determine the effectiveness of mobile applications in the
      rehabilitation of stroke survivors. METHODS: A literature search appraising the
      effectiveness of mobile applications in the rehabilitation of stroke survivors
      was performed on PubMed, Embase, Science Citation Index Expanded-SCIE, and EBSCO
      CINAHL from their inception until May 28th, 2017. Two reviewers independently
      screened the literature according to eligibility criteria, evaluated study
      quality, and collected data from the articles included. RESULTS: Of the 3574
      articles screened, 12 studies met the eligibility criteria of the systematic
      review. Of these, 2 studies were randomized controlled trials and the remaining
      10 were before-after studies, of which only 2 had control groups. The mobile
      applications encompassed 5 rehabilitation areas, 5 in physical function, 4 in
      language function, 2 in cognitive function, and 1 risk factor reduction. Of these
      12 studies, 9 reported significant improvements in function, while in 3 studies
      the descriptive statistics indicated favorable changes after intervention.
      CONCLUSIONS: Although the use of mobile applications in the rehabilitation of
      stroke survivors was effective, it is clear from this systematic review that more
      research is needed to verify their effectiveness.

PMID- 30209992
TI  - Editorial: Lipoprotein Subfractions in Patients with Acute Coronary Syndromes:
      Should we Reach Beyond LDL-C?

PMID- 30209993
TI  - Non-Steroidal Androgen Receptor Antagonists and Prostate Cancer: a Survey on
      Chemical Structures Binding this Fast-Mutating Target.
AB  - The androgen receptor (AR) pathway plays a major role both pathogenesis and
      progression of prostate cancer. In particular, AR is chiefly involved in the
      development of castration-resistant prostate cancer (CRPC) as well as in the
      resistance to the second-generation AR antagonist enzalutamide, and to the
      selective inhibitor of cytochrome P450 17A1 (CYP17A1) abiraterone. Several small
      molecules acting as AR antagonists have been designed and developed so far, also
      as a result of the ability of cells expressing this molecular target to rapidly
      develop resistance and turn pure receptor antagonists into ineffective or event
      detrimental molecules. This review covers a survey of most promising classes of
      non-steroidal androgen receptor antagonists, also providing insights on their
      mechanism of action and efficacy in treating prostate cancer.

PMID- 30209994
TI  - The Neurokinins: Peptidomimetic Ligand Design and Therapeutic Applications.
AB  - The neurokinins are indisputably essential neurotransmitters in numerous patho-
      and physiological events. Being widely distributed in the central nervous system
      (CNS) and peripheral tissues, their discovery rapidly promoted them to drugs
      targets. A necessity for molecular tools to understand the biological role of
      this class endogenous peptides and their receptors prompted the scientific
      community to design ligands displaying either agonist and antagonist activity at
      the three main neurokinin receptors, called NK1, NK2 and NK3. Several strategies
      were implemented for this purpose. With a preference for small non-peptidic
      ligands, many research groups invested efforts in synthesizing and evaluating a
      wide range of scaffolds, but only the NK1 antagonist Aprepitant (EMENDT) and its
      prodrug Fosaprepitant (IVEMENDT) have been approved by the Food Drug
      Administration (FDA) for the treatment of Chemotherapy-Induced and Post-Operative
      Nausea and Vomiting (CINV and PONV, respectively). While non-peptidic drugs
      showed limitations, especially in side effect control, peptidic and
      pseudopeptidic compounds progressively regained attention. Various strategies
      were implemented to modulate affinity, selectivity and activity of the newly
      designed ligands. Replacement of canonical amino acids, incorporation of
      conformational constraints, and fusion with non-peptidic moieties gave rise to
      families of ligands displaying individual or dual NK1, NK2 and NK3 antagonism,
      that ultimately was combined with non-neurokinin ligands (such as opioids) to
      target enhanced biological impact.

PMID- 30209988
TI  - BLM's balancing act and the involvement of FANCJ in DNA repair.
AB  - Timely recruitment of DNA damage response proteins to sites of genomic structural
      lesions is very important for signaling mechanisms to activate appropriate cell
      cycle checkpoints but also repair the altered DNA sequence to suppress
      mutagenesis. The eukaryotic cell is characterized by a complex cadre of players
      and pathways to ensure genomic stability in the face of replication stress or
      outright genomic insult by endogenous metabolites or environmental agents. Among
      the key performers are molecular motor DNA unwinding enzymes known as helicases
      that sense genomic perturbations and separate structured DNA strands so that
      replacement of a damaged base or sugar-phosphate backbone lesion can occur
      efficiently. Mutations in the BLM gene encoding the DNA helicase BLM leads to a
      rare chromosomal instability disorder known as Bloom's syndrome. In a recent
      paper by the Sengupta lab, BLM's role in the correction of double-strand breaks
      (DSB), a particularly dangerous form of DNA damage, was investigated. Adding to
      the complexity, BLM appears to be a key ringmaster of DSB repair as it acts both
      positively and negatively to regulate correction pathways of high or low
      fidelity. The FANCJ DNA helicase, mutated in another chromosomal instability
      disorder known as Fanconi Anemia, is an important player that likely coordinates
      with BLM in the balancing act. Further studies to dissect the roles of DNA
      helicases like FANCJ and BLM in DSB repair are warranted.

PMID- 30209996
TI  - Structural Characterization of Gallbladder Stones Using Energy Dispersive X-ray
      Spectroscopy and X-ray Diffraction.
AB  - AIM AND OBJECTIVE: Formation of the gallbladder stones is a common disease and a
      major health problem. The present study aimed to identify the structures of the
      most common types of gallbladder stones using X-ray spectroscopic techniques,
      which provide information about the process of stone formation. MATERIAL AND
      METHOD: Phase and elemental compositions of pure cholesterol and mixed gallstones
      removed from gallbladders of patients were studied using energy-dispersive X-ray
      spectroscopy combined with scanning electron microscopy analysis and X-ray
      diffraction. RESULTS: The crystal structures of gallstones which coincide with
      standard patterns were confirmed by X-ray diffraction. Plate-like cholesterol
      crystals with laminar shaped and thin layered structures were clearly observed
      for gallstone of pure cholesterol by scanning electron microscopy; it also
      revealed different morphologies from mixed cholesterol stones. Elemental analysis
      of pure cholesterol and mixed gallstones using energy-dispersive X-ray
      spectroscopy confirmed the different formation processes of the different types
      of gallstones. CONCLUSION: The method of fast and reliable X-ray spectroscopic
      techniques has numerous advantages over the traditional chemical analysis and
      other analytical techniques. The results also revealed that the X-ray
      spectroscopy technique is a promising technique that can aid in understanding the
      pathogenesis of gallstone disease.

PMID- 30209995
TI  - Mesenchymal Stem Cell Therapy For Ischemic Heart Disease: Advances And
      Challenges.
AB  - Ischemic heart disease (IHD) has been recognized as the main cause of mortality
      in the modern world. Application of cell therapy technologies for the IHD
      treatment has been actively studied from the beginning of 2000s. The review is
      dedicated to the use of mesenchymal stem cells (MSC) in the therapy of IHD. The
      strategies of the MSC modification in vitro for improvement of their regenerative
      potential are extensively discussed, including preconditioning to enhance the
      cell survival, boosting their paracrine effect, manipulating their cardiomyogenic
      differentiation. The optimization of the MSC delivery and opportunities related
      to the use of biomaterials as cell carriers are also discussed. The results of
      the most important clinical studies on the MSC-based IHD therapy are presented,
      including those completed and published in the literature and the ongoing
      clinical trials registered at clinicaltrials.gov by June, 2018.

PMID- 30209997
TI  - A Brief Survey of Machine Learning Application in Cancerlectin Identification.
AB  - Proteins with at least one carbohydrate recognition domain are lectins that can
      identify and reversibly interact with glycan moiety of glycoconjugates or a
      soluble carbohydrate. It has been proved that lectins can play various vital
      roles in mediating signal transduction, cell-cell recognition and interaction,
      immune defense, and so on. Most organisms can synthesize and secret lectins. A
      portion of lectins closely related to diverse cancers, called cancerlectins, are
      involved in tumor initiation, growth and recrudescence. Cancerlectins have been
      investigated for their applications in the laboratory study, clinical diagnosis
      and therapy, and drug delivery and targeting of cancers. The identification of
      cancerlectin genes from a lot of lectins is helpful for dissecting cancers.
      Several cancerlectin prediction tools based on machine learning approaches have
      been established and have become an excellent complement to experimental methods.
      In this review, we comprehensively summarize and expound the indispensable
      materials for implementing cancerlectin prediction models. We hope that this
      review will contribute to understanding cancerlectins and provide valuable clues
      for the study of cancerlectins. Novel systems for cancerlectin gene
      identification are expected to be developed for clinical applications and gene
      therapy.

PMID- 30209998
TI  - Deep Forest-based Prediction of Protein Subcellular Localization.
AB  - MOTIVATION: Knowledge of the correct protein subcellular localization is
      necessary for understanding the function of a protein and revealing the mechanism
      of many human diseases due to protein subcellular mislocalization, which is
      required before approaching gene therapy to treat a disease. In addition, it is
      well-known that the gene therapy is an effective way to overcome disease by
      targeting a gene therapy product to a specific subcellular compartment. Deep
      neural networks to predict protein function have become increasingly popular due
      to large increases in the available genomics data due to its strong superiority
      in the non-linear classification ability. However, they still have some drawbacks
      such as too many hyper-parameters and sufficient amount of labeled data. RESULTS:
      We present a deep forest-based protein location algorithm relying on sequence
      information. The prediction model uses a random forest network with a multi
      layered structure to identify the subcellular regions of protein. The model was
      trained and tested on a latest UniProt releases protein dataset, and we
      demonstrate that our deep forest predict the subcellular location of proteins
      given only the protein sequence with high accuracy, outperforming the current
      state-of-art algorithms. Meanwhile, unlike the deep neural networks, it has a
      significantly smaller number of parameters and is much easier to train.

PMID- 30209999
TI  - Neuroprotection by Human Dental Pulp Mesenchymal Stem Cells: From Billions to
      Nano.
AB  - INTRODUCTION: Mesenchymal Stem Cell (MSC) therapy in recent years has gained
      significant attention. Though the functional outcomes following MSC therapy for
      neurodegenerative diseases are convincing, various mechanisms for the functional
      recovery are being debated. Nevertheless, recent studies convincingly
      demonstrated that recovery following MSC therapy could be reiterated with MSC
      secretome per se thereby shifting the dogma from cell therapy to cell "based"
      therapy. In addition to various functional proteins, stem cell secretome also
      includes extracellular membrane vesicles like exosomes. Exosomes which are of
      "Nano" size have attracted significant interest as they can pass through the
      bloodbrain barrier far easily than macro size cells or growth factors. Exosomes
      act as a cargo between cells to bring about significant alterations in target
      cells. As the importance of exosomes is getting unveil, it is imperial to carry
      out a comprehensive study to evaluate the neuroprotective potential of exosomes
      as compared to conventional co-culture or total condition medium treatments.
      OBJECTIVE: Thus, the present study is designed to compare the neuroprotective
      potential of MSC derived exosomes with MSC-condition medium or neuron-MSC-co
      culture system against kainic acid induced excitotoxicity in in vitro condition.
      The study also aims at comparing the neuroprotective efficacy of
      exosomes/condition medium/co-culture of two MSC viz., neural crest derived human
      Dental Pulp Stem Cells (hDPSC) and human Bone-Marrow Mesenchymal Stem Cells (hBM
      MSC) to identify the appropriate MSC source for treating neurodegenerative
      diseases. RESULT: Our results demonstrated that neuroprotective efficacy of MSC
      exosomes is as efficient as MSC-condition medium or neuron-MSC co-culture system
      and treating degenerating hippocampal neurons with all three MSC based approaches
      could up-regulate host's endogenous growth factor expressions and prevent
      apoptosis by activating cell survival PI3K-B-cell lymphoma-2 (Bcl-2) pathway.
      CONCLUSION: Thus, the current study highlights the possibilities of treating
      neurodegenerative diseases with "Nano" size exosomes as opposed to transplanting
      billions of stem cells which inherit several disadvantages.

PMID- 30210000
TI  - Insights on the Use of Nanocarriers for Acne Alleviation.
AB  - Among the common myths in the cosmetics industry is the perception that acne only
      happens to teenagers, and specifically to females. However, acne is neither
      limited to a specific age, nor to a certain gender, it creates a stressful
      problem for many people. Many chemical treatments for acne were proven to be
      successful, but when administered as such, they showed many adverse effects,
      starting from itching to skin dryness and inflammation. Natural remedies have
      also been explored for acne treatment, and despite their safety, they suffered
      many stability problems attributed to their physicochemical properties, creating
      an obstacle for their topical delivery. Therefore, many nanocarriers were used to
      deliver those chemical and natural remedies topically to maximize their
      therapeutic potential in acne treatment. The present review discusses the
      different nanocarriers which were proven successful in improving the acne
      lesions, focusing on vesicular, lipidic, and polymeric systems.

PMID- 30210002
TI  - Oxazolone-1,2,3-Triazole Hybrids: Design, Synthesis and Antimicrobial Evaluation.
AB  - BACKGROUND: Oxazolones and 1,2,3-triazoles are among the extensively studied
      heterocycles in medicinal chemistry. Both of these moieties are reported to
      possess a broad spectrum of biological activity including antimicrobial.
      OBJECTIVE: The objective of the current work is to design, synthesize and
      antimicrobial evaluation of some new oxazolone-1,2,3-triazole hybrids. METHODS:
      The designed oxazolone-1,2,3-triazole hybrids were synthesized using copper(I)
      catalyzed azide-alkyne cycloaddition. The antimicrobial evaluation was carried
      out using serial dilution method. RESULTS: Most of the synthesized hybrids showed
      significant antimicrobial properties. Some of the compounds were found to be
      possessing better or comparable activity to that of the standards used. The
      docking simulations results are also in agreement with the antimicrobial activity
      data. CONCLUSION: Sixteen new hybrids were synthesized and tested in vitro for
      their antimicrobial activity. Some of the tested compounds exhibited promising
      antimicrobial activity and could be utilized for the development of the lead
      compounds for new and more potent antimicrobial drugs.

PMID- 30210003
TI  - Smoking and Endothelial Dysfunction.
AB  - Cigarette smoking is one the most important health concerns worldwide. Even
      though the rate of smoking is declining in developed countries, it is still
      experiencing growth in developing regions. Many studies have examined the
      relationship between smoking, as an established risk factor, and cardiovascular
      diseases. We provide an updated review of the underlying mechanisms of smoking
      induced cardiovascular diseases, with a focus on the relationship between smoking
      and oxidative stress, particularly from the perspective of endothelial cell
      dysfunction. We review smoking-induced oxidative stress as a trigger for a
      generalized vascular inflammation associated with cytokine release, adhesion of
      inflammatory cells and, ultimately, disruption of endothelial integrity as a
      protective barrier layer. We also briefly discuss the harms related to the vaping
      of electronic cigarettes, which many erroneously consider as a safe alternative
      for smoking. We conclude that even though e-cigarette could be a helpful device
      during the transition period of cigarette quitting, it is by no means a safe
      substitute.

PMID- 30210001
TI  - Crossed Cerebellar Diaschisis in Alzheimer's Disease.
AB  - BACKGROUND: We describe the phenomenon of crossed cerebellar diaschisis (CCD) in
      four subjects diagnosed with Alzheimer's disease (AD) according to the National
      Institute on Aging - Alzheimer Association (NIA-AA) criteria, in combination with
      18F-FDG PET and 11C-PiB PET imaging. METHODS: 18F-FDG PET showed a pattern of
      cerebral metabolism with relative decrease most prominent in the frontal-parietal
      cortex of the left hemisphere and crossed hypometabolism of the right cerebellum.
      11C-PiB PET showed symmetrical amyloid accumulation, but a lower relative tracer
      delivery (a surrogate of relative cerebral blood flow) in the left hemisphere.
      CCD is the phenomenon of unilateral cerebellar hypometabolism as a remote effect
      of supratentorial dysfunction of the brain in the contralateral hemisphere. The
      mechanism implies the involvement of the cortico-ponto-cerebellar fibers. The
      pathophysiology is thought to have a functional or reversible basis but can also
      reflect in secondary morphologic change. CCD is a well-recognized phenomenon,
      since the development of new imaging techniques, although scarcely described in
      neurodegenerative dementias. RESULTS: To our knowledge this is the first report
      describing CCD in AD subjects with documentation of both 18F-FDG PET and 11C-PiB
      PET imaging. CCD in our subjects was explained on a functional basis due to
      neurodegenerative pathology in the left hemisphere. There was no structural
      lesion and the symmetric amyloid accumulation did not correspond with the
      unilateral metabolic impairment. CONCLUSION: This suggests that CCD might be
      caused by non-amyloid neurodegeneration. The pathophysiological mechanism,
      clinical relevance and therapeutic implications of CCD and the role of the
      cerebellum in AD need further investigation.

PMID- 30210004
TI  - Molecular Docking, G-QSAR studies, Synthesis and Anticancer screening of some New
      2-Phenazinamines as Bcr-Abl Tyrosine kinase Inhibitors.
AB  - The computational studies on 2-phenazinamines with their protein targets have
      been carried out to design compounds with potential anticancer activity. This
      strategy of designing compounds possessing selectivity over specific tyrosine
      kinase has been achieved through G-QSAR and molecular docking studies. The
      objective of this research has been to design newer 2-phenazinamine derivatives
      as Bcr-Abl tyrosine kinase inhibitors by G-QSAR, molecular docking studies
      followed by wet lab studies along with evaluation of their anticancer potential.
      Computational chemistry was done by using VLife MDS 4.3 and Autodock 4.2 followed
      by wet lab experiments for synthesizing 2-phenazinamine derivatives. The chemical
      structures of ligands in 2D were drawn by employing Chemdraw 2D Ultra 8.0 and
      were converted into 3D. These were optimised by using semi-empirical method
      called MOPAC. The protein structure was retrieved from RCSC protein data bank as
      PDB file. The binding interactions of protein and ligands was done by using
      PYMOL. The molecular properties of the designed compounds were predicted in
      silico by using Osiris property explorer. The parent compound 2-phenazinamine was
      synthesized by reduction of 2,4-dinitro-N-phenyl-benzenamine in the presence of
      tin chloride followed by cyclization in presence of nitrobenzene and magnesium
      sulfate. The derivatization at amino function of 2-phenazinamine was performed by
      treating parent compound with various aldehydes in the presence of
      dicyclohexylcarbodiimide (DCC) and urea to afford 2-(2-chlorophenyl)-3-(phenazin
      2-yl) thiazolidin-4-one. Another series of derivatives was prepared by reacting
      parent compound with different aldehydes in the presence of p-toluylsulphonic
      acid, diphydropyridine and benzene sulfonyl chloride to afford benzenesulfonyl-N
      (2-chlorobenzyl)-phenazin-2-amine. All the derivatives were tested for invitro
      anticancer activity on K562 human chronic myelogenous leukemia cell line by
      employing MTT assay method. The developed G-QSAR models were found to be
      statistically significant with respect to training (r2=0.8074), cross-validation
      (q2=0.6521), and external validation (pred_r2=0.5892). The best developed G-QSAR
      model suggested that the XlogP values of phenazinamine derivatives were highly
      influential in determining biological activity. Docking studies showed binding
      interactions of some derivatives with > 30% higher binding energy values than
      standard doxorubicin. The standard drug was found to exhibit binding energy -
      6.79 kcal/mol and the derivatives 5b and 6c exhibited binding energy of - 7.46
      and - 8.51; respectively. The lower energy values obtained for these derivatives
      indicate favourable interaction towards protein binding site as compared to
      standard doxorubicin. The findings obtained from G-QSAR and docking studies, were
      utilized for designing newer phenazinamine derivatives. The synthesis of these 2
      phenazinamine derivatives (5a-m) is reported to be obtained from 2,4
      dinitrodiphenylamine by applying appropriate synthetic route. These compounds 5a
      m were further evaluated for anticancer activities. Compounds 5b, 6c were
      observed to possess good lipophilicity and were found to exhibit better activity
      than other compounds in the series, although less than standard doxorubicin. The
      studies of G-QSAR and molecular docking predicted better anticancer activity for
      the synthesized thiazolidones and benzenesulfonyl derivatives of phenazinamines
      as compared to standard doxorubicin. It is therefore surmised that the molecular
      manipulations at appropriate sites suggested by structure-activity relationship
      data will prove to be beneficial to give enhanced anticancer potential. Among the
      synthesized derivatives, compounds 5b and 6c showed better cytotoxic activity
      against K562 cancer cell line when compared to other compounds of the series,
      although less than standard doxorubicin.

PMID- 30210005
TI  - Electrocardiographic Assessment and Genetic Analysis in Neonates: a Current Topic
      of Discussion.
AB  - BACKGROUND: Sudden death of a newborn is a rare entity, which may be caused by
      genetic cardiac arrhythmias. Among these diseases, Long QT syndrome is the most
      prevalent arrhythmia in neonates, but other diseases such as Brugada syndrome,
      Short QT syndrome and Catecholaminergic Polymorphic Ventricular Tachycardia also
      cause sudden death in infants. All these entities are characterized by well-known
      alterations in the electrocardiogram and the first symptom of the disease may be
      an unexpected death. Despite the low prevalence of these diseases, the
      performance of an electrocardiogram in the first hours or days after birth could
      help identify these electrical disruptions and adopt preventive measures. In
      recent years, there has been an important impulse by some experts in the
      scientific community towards the initiation of a newborn electrocardiogram
      screening program, for the detection of these electrocardiographic abnormalities.
      In addition, the use of genetic analysis in neonates could identify the cause of
      these heart alterations. Identification of relatives carrying the genetic
      alteration associated with the disease allows adoption of measures to prevent
      lethal episodes. CONCLUSION: Recent technological advances enable a comprehensive
      genetic screening of a large number of genes in a cost-effective way. However,
      the interpretation of genetic data and its translation into clinical practice are
      the main challenge for cardiologists and geneticists. However, there is important
      controversy as to the clinical value, and cost effectiveness of the use of
      electrocardiogram as well as of genetic testing to detect these cases. Our review
      focuses on these current matters of argue.

PMID- 30210006
TI  - The clinical trials of mesenchymal stem cell therapy in skin diseases: an update
      and concise review.
AB  - Skin is one of the crucial body organs which its anatomy and physiology are
      linked with various disorders including congenital or acquired diseases.
      Nowadays, mesenchymal stem cell (MSCs)-based therapy has become a promising
      therapeutic field, which is expected to help in the treatment of the most costly
      and incurable diseases. However, it could be questioned whether the use of MSCs
      has improved in clinical trials studies and diseases treatment. In this study, we
      review the clinical trials using MSCs in skin diseases. A remarkable number of
      clinical trial studies are in progress in this field, however, some have had
      early benefits to patients. We discuss here relevant papers and ongoing clinical
      trials that address MSC's therapeutic goals for various skin disorders, while
      this review can be very useful for both dermatologists and basic skin
      researchers, with the aim of contributing to stem cell-based therapeutic research
      in the area of skin disorders.

PMID- 30210007
TI  - Amarogentin as topical anticancer and anti-infective potential: Scope of lipid
      based vesicular in its effective delivery.
AB  - There is the need of development of liposomes based nanomedicines formulation for
      the better efficacy and safety of the available drugs in the market. Liposomes
      have various applications in the field of pharmaceutical and medical field for
      their drug target potential, diagnostic importance and imaging techniques.
      Natural plant based drugs and their derivative have been used in the medicine,
      nutraceuticals, perfumery, cosmetic and beverages industry. More than half of the
      prescribed drugs in the worldwide are mainly derived from different natural
      sources. Development of plant derived product is an emerging field of food,
      pharmaceutical and health industries. Plants belonging to Gentianaecae family are
      well known for their bitter taste and Swertia chirata is one of best plant among
      them. Various active phytochemical of Swertia chirata are bitter secoiridoids
      like gentiopicroside, amarogentin, swertiamarin, isovitexin and isogentisin.
      Peoples are using different species of Swertia in the form of decoction,
      infusion, paste and juice for the treatment of fever and enteric diseases.
      Swertia chirata possess anticarcinogenic, antioxidative, hypoglycemic,
      antihepatotoxic, antimalarial, anti-inflammatory and antimicrobial activities.
      Amarogentin is a bitter secoiridoid glycoside present in Swertia chirata plant is
      an activator of human bitter taste receptor. Pharmacologically amarogentin is
      having antibacterial, antihepatitis, anticholinergic and chemopreventive
      activities, moreover amarogentin has been proven for their anti-lieshmanial
      activity. Other studies also suggested that amarogentin act against liver
      carcinogenesis, skin carcinogenesis and reduced tumour progression. In the
      present review, we have collected and compiled the data's regarding biological
      sources, ethnomedicinal uses, phytochemistry, anticancer and anti-infective
      potential of amarogentin. For better understanding of various aspects of
      amarogentin we have also discussed Swertia chirayita in very concise manner.
      Further data related to various patents on amarogentin were also discussed in
      this manuscript. However we also admit that new advance biological research will
      also increase the medicinal and pharmacological value of amarogentin. Information
      regarding the chemistry of amarogentin, its biological sources, bioavailability
      as a pharmacological agent for the treatment and management of skin disorders and
      various forms of cancers will be beneficial to the scientist of the medicinal
      field.

PMID- 30210008
TI  - Comparison and Impact of Short-Term Use of Some Non-Aspirin NSAIDs on Bleeding
      Time of Mice.
AB  - BACKGROUND: Non-Steroidal Anti Inflammation Drugs (NSAIDs) are a class of drugs
      that have been shown to be effective in reducing pain and the most prescribing
      around the world. But this group impair hematological aspects that may lead to
      life-threatening. OBJECTIVE: The objective of the study is to determine the
      comparison and impact of short-term use of some non-aspirin NSAIDs on bleeding
      time parameter. METHOD: Each groups contained 4 animals were given the test drugs
      (normal group without any treatment, ketoprofen 0,26 mg/ 20 g BW of mice twice
      daily, ketorolac 0,078 mg/ 20 g BW of mice twice daily, diclofenac sodium 0,13
      mg/ 20 g BW of mice twice daily, piroxicam 0,052 mg/ 20 g BW of mice once daily,
      mefenamic acid 1,3 mg/ 20 g BW of mice thrice daily, meloxicam 0,039 mg/ 20 g BW
      of mice once daily, celecoxib 0,52 mg/ 20 g BW of mice once daily, ibuprofen 1,04
      mg/ 20 g BW of mice thrice daily and paracetamol 1,3 mg/ 20 g BW of mice thrice
      daily) for 5 days. The determination of bleeding time was conduct one hour after
      the last administration of the test drugs in the 5th day. RESULTS: All test group
      showed an elevation of the bleeding time as 59,78%, 156,50%, 108,73%, 99,96%,
      22,59%, 85,46%, 69,66%, 42,24%, 45,08% for meloxicam, ketoprofen, ketorolac,
      diclofenac sodium, paracetamol, piroxicam, mefenamic acid, ibuprofen and
      celecoxib compared to normal groups, respectively. Ketoprofen and ketorolac
      showed significant different (p<0.05) on an elevation of the bleeding time to the
      normal group. Furthermore, ketoprofen showed significant different (p<0.05) on an
      elevation of the bleeding time to meloxicam, paracetamol, ibuprofen ,and
      celecoxib. CONCLUSION: Ketorolac showed the highest of an elevation of bleeding
      time and ibuprofen is the lowest of NSAIDs group. Paracetamol was the lowest of
      bleeding time than any test groups. Celecoxib (cyclooxygenase-2 selective) showed
      an elevation of the bleeding time compared to the normal group, although wasn't
      significant (p>0,05) and this may indicate inhibition of celecoxib to
      cyclooxygenase-1.

PMID- 30210009
TI  - Formation of a toxic quinoneimine metabolite from diclofenac: a quantum chemical
      study.
AB  - Diclofenac is a non-steroidal antiinflammatory drug. It is predominantly
      metabolized by CYP2C9. 4-hydroxydiclofenac and its quinoneimine are the
      metabolites of diclofenac. However, few numbers of serious cases of idiosyncratic
      hepatotoxicity due to diclofenac metabolism were reported. The formation of the
      quinoneimine metabolite was found to be responsible for this idiosyncratic
      toxicity. Quinoneimine is an over-oxidized metabolite of diclofenac. In this
      work, computational studies were conducted to detail the formation of a
      quinoneimine metabolite from diclofenac. Further, the idiosyncratic toxicity of
      quinoneimine due to its reactivity was also investigated by quantum chemical
      analysis. The results demonstrate the possibility of formation of quinoneimine
      metabolite due to various factors that are involved in the metabolism of
      diclofenac. The present study may provide the structural in-sights during the
      drug development processes to avoid the metabolism directed idiosyncratic
      toxicity.

PMID- 30210010
TI  - Skin targeting of oxiconazole nitrate loaded nanostructured lipid carrier gel for
      fungal infections.
AB  - The progression of fungal infections can be rapid and serious due to compromising
      with immune function. They may cause liver damage, affect estrogen levels or may
      cause allergic reactions. Oxyconazole nitrate (OCXN) is a broad spectrum commonly
      used antifungal drug. It acts by erogosterol biosynthesis inhibition, which
      causes lysis of fungal cell membrane because of changes in both membrane
      integrity and fluidity and direct membrane damage of fungal cells. However, its
      poor water solubility and short half-life (3-5 h) limit its applications. This
      study aimed to develop and evaluate OXZN-loaded nanostructured lipid carrier
      (NLC) to improve its solubility and prolong its release for the treatment of
      fungal infection via topical administration. OXZN-NLC was prepared by
      ultrasonication method using 32 full factorial design. Glyceryl monostearate
      (GMS) (X1) and oleic acid (X2) were used as independent variables and particle
      size (PS) and percentage entrapment efficiency (% EE) as dependent variables. The
      OXZN NLCs were characterized for particle size, particle morphology and
      entrapment efficiency. The mean diameter of optimized OXZN-NLCs was found to be
      124 +/- 2 nm. Spherical shape and size were confirmed using scanning electron
      microscopy (SEM). Skin deposition study showed about 82.74% deposition as
      compared with the marketed formulation that showed 68.42% deposition. The
      developed NLCs show a sustained release pattern and high drug disposition in the
      infected area. Hence, OXZN-NLC could be a potential alternative for the treatment
      of topical fungal infection after clinical evaluation in near future.

PMID- 30210011
TI  - Myotonic Discharges in Anti-MuSK Myasthenia.

PMID- 30210012
TI  - A systematic review of the Trypanosoma cruzi genetic heterogeneity, host immune
      response and genetic factors as plausible drivers of chronic chagasic
      cardiomyopathy.
AB  - Chagas disease is a complex tropical pathology caused by the kinetoplastid
      Trypanosoma cruzi. This parasite displays massive genetic diversity and has been
      classified by international consensus in at least six Discrete Typing Units
      (DTUs) that are broadly distributed in the American continent. The main clinical
      manifestation of the disease is the chronic chagasic cardiomyopathy (CCC) that is
      lethal in the infected individuals. However, one intriguing feature is that only
      30-40% of the infected individuals will develop CCC. Some authors have suggested
      that the immune response, host genetic factors, virulence factors and even the
      massive genetic heterogeneity of T. cruzi are responsible of this clinical
      pattern. To date, no conclusive data support the reason why a few percentages of
      the infected individuals will develop CCC. Therefore, we decided to conduct a
      systematic review analysing the host genetic factors, immune response, cytokine
      production, virulence factors and the plausible association of the parasite DTUs
      and CCC. The epidemiological and clinical implications are herein discussed.

PMID- 30210013
TI  - Paragonimus and paragonimiasis in West and Central Africa: unresolved questions.
AB  - Paragonimiasis, human lung fluke disease, is a foodborne anthropozoonosis caused
      by the trematodes assigned to Paragonimus and is regarded by the World Health
      Organization as a Neglected Tropical Disease (NTD). The life cycle of this
      medically important parasite centres on a complex freshwater biological community
      that includes two intermediate hosts: a mollusc and a decapod, usually a
      brachyuran. Although there is a perception that the biology, symptoms, diagnosis
      and treatment of Paragonimus is well understood, in reality, this is not the
      case, especially in Africa. Much remains unknown concerning the life-cycle of the
      parasite, its transmission, the current epidemiology of the disease, diagnosis
      and the effectiveness of treatment. Furthermore, cases of paragonimiasis may be
      misdiagnosed as resistant tuberculosis (TB) because of the similar pulmonary
      symptoms and no remission after anti TB therapy. The endemic foci of human
      paragonimiasis in Africa have been reported mainly in the forest zones of Upper
      Guinea (Liberia, Guinea and Ivory Coast) and Lower Guinea (Nigeria, Cameroon,
      Equatorial Guinea and Gabon). Despite the perceived medical importance of
      paragonimiasis, relatively little attention has been paid to this NTD since its
      discovery in Africa in the 1960s. This review focuses on the current
      understanding of the life cycle and transmission of Paragonimus in Africa,
      discusses its diagnosis and public health importance and highlights many
      outstanding gaps in the knowledge that still exist for this NTD.

PMID- 30210014
TI  - Occurrence of Schistosoma bovis on Pemba Island, Zanzibar: implications for
      urogenital schistosomiasis transmission monitoring - CORRIGENDUM.

PMID- 30210015
TI  - Preparing for a Foreign Animal Disease Outbreak Using a Novel Tabletop Exercise.
AB  - : IntroductionForeign animal disease (FAD) outbreaks can have devastating
      impacts, but they occur infrequently in any specific sector anywhere in the
      United States (US). Training to proactively discuss implementation of control and
      prevention strategies are beneficial in that they provide stakeholders with the
      practical information and educational experience they will need to respond
      effectively to an FAD. Such proactive approaches are the mission of the Secure
      Food System (SFS; University of Minnesota; St. Paul, Minnesota USA). METHODS: The
      SFS exercises were designed as educational activities based on avian influenza
      (AI) outbreaks in commercial poultry scenarios. These scenarios were created by
      subject matter experts and were based on epidemiology reports, risk pathway
      analyses, local industry practices, and site-specific circumstances. Target
      audiences of an exercise were the groups involved in FAD control: animal
      agriculture industry members; animal health regulators; and diagnosticians.
      Groups of industry participants seated together at tables represented fictional
      poultry premises and were guided by a moderator to respond to an on-farm
      situation within a simulated outbreak. The impact of SFS exercises was evaluated
      through interviews with randomized industry participants and selected table
      moderators. Descriptive statistics and qualitative analyses were performed on
      interview feedback. RESULTS: Eleven SFS exercises occurred from December 2016
      through October 2017 in multiple regions of the US. Exercises were conducted as
      company-wide, state-wide, or regional trainings. Nine were based on highly
      pathogenic avian influenza (HPAI) outbreaks and two focused on outbreaks of co
      circulating HPAI and low pathogenicity avian influenza (LPAI). Poultry industry
      participants interviewed generally found attending an SFS exercise to be useful.
      The most commonly identified benefits of participation were its value to people
      without prior outbreak experience and knowledge gained about Continuity of
      Business (COB)-permitted movement. After completing an exercise, most
      participants evaluated their preparedness to respond to an outbreak as somewhat
      to very ready, and more than one-half reported their respective company or farms
      had discussions or changed actions due to participation. CONCLUSION: Evaluation
      feedback suggests the SFS exercises were an effective training method to
      supplement preparedness efforts for an AI outbreak. The concept of using multi
      faceted scenarios and multiple education strategies during a tabletop exercise
      may be translatable to other emergency preparedness needs.Linskens EJ, Neu AE,
      Walz EJ, St. Charles KM, Culhane MR, Ssematimba A, Goldsmith TJ, Halvorson DA,
      Cardona CJ. Preparing for a foreign animal disease outbreak using a novel
      tabletop exercise.

PMID- 30210016
TI  - Painful Proximal Weakness and HyperCKemia Related to Intravenous Loading of
      Phenytoin.

PMID- 30210017
TI  - Comparison between electroporation and polyfection in pig sperm: efficiency and
      cell viability implications.
AB  - SummaryThe aim of this study was to optimize protocols for electroporation (EP)
      and polyfection (PLF) using polyethyleneimine (PEI) for pig sperm transfection
      and to determine which method was the most efficient. For EP standardization,
      different voltages, amounts and times of electric pulses were tested using
      propidium iodide (PI) as reporter. For PLF standardization, different
      concentrations of fluorescein isothiocyanate (FITC)-labelled PEI (PEI/FITC) were
      incubated with sperm for different periods of time. Flow cytometry was performed
      to evaluate the best protocol in terms of cell viability, including cytoplasmic
      membrane, acrosome, chromatin integrities and mitochondrial potential using the
      FITC probe, PI, acridine orange (AO) and JC1. Transfections with the plasmid
      pmhyGENIE-5 were carried out under optimum conditions for each procedure (EP: 500
      volts, 500 MUs and two pulses; PLF: PEI 0.5 mg/ml and incubation time 10 min).
      Transfection efficacy was assessed by fluorescence in situ hybridization (FISH).
      A lower transfection rate was observed for sperm in the control group (17.8%)
      compared with EP (36.7%), with PLF (76.8%) being the most efficient. These
      results suggest that the EP and PEI could be an efficient and low cost
      transfection method for swine sperm. Notably, treated cells showed higher
      plasmatic the membrane damage (PMD) and/or acrosome damage (AD) indexes,
      therefore the combination of this procedure with biotechniques that facilitate
      fecundation (i.e. in vitro fertilization or intracytoplasmic sperm injection) or
      even inclusion of antioxidant or anti-apoptotic drugs to improve spermatozoa
      viability would be important.

PMID- 30210018
TI  - [Drug management of pediatric acute respiratory distress syndrome].
AB  - This article reviewed the Consensus Recommendations on Pediatric Acute
      Respiratory Distress Syndrome (ARDS) from the Pediatric Acute Lung Injury
      Consensus Conference in 2015 and the literature related to drug management of
      ARDS. The main points of drug management of pediatric ARDS were summarized.

PMID- 30210019
TI  - [Application of extracorporeal membrane oxygenation in children with acute
      respiratory distress syndrome].
AB  - The children with acute respiratory distress syndrome (ARDS) usually require
      ventilatory support treatment. At present, lung protective ventilation strategy
      is recommended for the treatment of ARDS. Extracorporeal membrane oxygenation
      (ECMO) can improve oxygenation and remove carbon dioxide by extracorporeal
      circuit, and can partially or completely take over cardiopulmonary function. ECMO
      support showed many advantages in treating severe ARDS, such as reducing
      ventilator-induced lung injury and correcting hypoxemia. Over the past few years,
      there has been an increase in the use of ECMO for ARDS in children. This paper
      reviews the applications of ECMO for the treatment of ARDS in children.

PMID- 30210020
TI  - [Lung recruitment maneuvers and positive end-expiratory pressure titration in
      children with acute respiratory distress syndrome].
AB  - The application of small tidal volume and the limitation of airway pressure
      during mechanical ventilation in acute respiratory distress syndrome (ARDS) are
      well accepted. Lung recruitment and positive end-expiratory pressure (PEEP)
      titration can improve oxygenation and protect the lungs. However, the approaches
      of lung recruitment and PEEP titration remain controversial. This article reviews
      the lung recruitment maneuvers and PEEP titration in children with ARDS.

PMID- 30210021
TI  - [Application of noninvasive ventilation in children with acute respiratory
      distress syndrome].
AB  - Acute respiratory distress syndrome (ARDS) is a common critical illness in
      children and has high incidence and mortality rates among critically ill
      pediatric patients. Noninvasive ventilation has become a common treatment method
      for ARDS because of its unique features. This article reviews the research status
      in the application of noninvasive ventilation in children with ARDS.

PMID- 30210022
TI  - [Advances in the diagnosis and treatment of pediatric acute respiratory distress
      syndrome].
AB  - Pediatric acute respiratory distress syndrome (ARDS) is an important cause of
      deaths in critically ill children admitted to the pediatric intensive care unit.
      Although lung-protective ventilation improves the prognosis of pediatric ARDS,
      the mortality rate of children with moderate or severe ARDS is still high. Given
      that the epidemiology, treatment, and prognosis of pediatric ARDS are different
      from those of adult ARDS, pediatric ARDS was first defined in the 2015 Pediatric
      Acute Lung Injury Consensus Conference. Early diagnosis and appropriate clinical
      management of ARDS are still great challenges for pediatric critical care
      medicine. This paper focuses on the definition, epidemiology, and management of
      pediatric ARDS.

PMID- 30210023
TI  - [A review on neonatal acute respiratory distress syndrome].
AB  - Acute respiratory distress syndrome (ARDS) is a common clinical critical disease
      and is one of the main causes of death and disability in neonates. The etiology
      and pathogenesis of neonatal ARDS are complicated. It is an acute pulmonary
      inflammatory disease caused by the lack of pulmonary surfactant (PS) related to
      various pathological factors. It is difficult to distinguish neonatal ARDS from
      other diseases. At present, there is no specific treatment method for this
      disease. Respiratory support, PS replacement, extracorporeal membrane
      oxygenation, nutrition support and liquid management are main treatment
      strategies. This paper reviews the research advance in etiology, clinical
      characteristics, diagnosis and treatment strategies of neonatal ARDS.

PMID- 30210024
TI  - [A comparative study of two ventilation modes in the weaning phase of preterm
      infants with respiratory distress syndrome].
AB  - OBJECTIVE: To compare the efficacy between synchronized intermittent mandatory
      ventilation (SIMV) and pressure support ventilation with volume guarantee
      (PSV+VG) in the weaning phase of preterm infants with respiratory distress
      syndrome (RDS). METHODS: Forty preterm infants with RDS who were admitted to the
      neonatal intensive care unit between March 2016 and May 2017 were enrolled as
      subjects. All infants were born at less than 32 weeks' gestation and received
      mechanical ventilation. These patients were randomly and equally divided into
      SIMV group and PSV+VG group in the weaning phase. Ventilator parameters, arterial
      blood gas, weaning duration (from onset of weaning to extubation), duration of
      nasal continuous positive airway pressure (NCPAP) after extubation, extubation
      failure rate, the incidence rates of pneumothorax, patent ductus arteriosus (PDA)
      and bronchopulmonary dysplasia (BPD), and the mortality rate were compared
      between the two groups. RESULTS: The PSV+VG group had significantly decreased
      mean airway pressure, weaning duration, duration of NCPAP after extubation, and
      extubation failure rate compared with the SIMV group (P<0.05). There were no
      significant differences in arterial blood gas, mortality, or incidence rates of
      pneumothorax, PDA and BPD between the two groups (P>0.05). CONCLUSIONS: For
      preterm infants with RDS, the PSV+VG mode may be a relatively safe and effective
      mode in the weaning phase. However, multi-center clinical trials with large
      sample sizes are needed to confirm the conclusion.

PMID- 30210025
TI  - [Value of transesophageal atrial pacing in neonates with tachyarrhythmia].
AB  - OBJECTIVE: To study the value of transesophageal atrial pacing (TEAP) in neonates
      with tachyarrhythmia. METHODS: The clinical data of 26 neonates with
      tachyarrhythmia who underwent TEAP electrophysiological examination or
      cardioversion were collected. RESULTS: Of the 26 neonates, 15(58%) were diagnosed
      with atrioventricular reentrant tachycardia, 3(12%) were diagnosed with sinus
      tachycardia, 3(12%) were diagnosed with ventricular tachycardia, 2(8%) were
      diagnosed with fast/slow atrioventricular nodal reentrant tachycardia, 2(8%) were
      diagnosed with atrial tachycardia, and 1(4%) was diagnosed with sinus tachycardia
      with ventricular preexcitation. Overdrive suppression was performed for 22
      neonates, among whom 18 achieved successful cardioversion, and 2 with atrial
      tachycardia and 2 with ventricular tachycardia failed to restore sinus rhythm.
      CONCLUSIONS: TEAP is helpful to the diagnosis of tachyarrhythmia in neonates and
      can bring about a high rate of cardioversion success.

PMID- 30210026
TI  - [Value of simultaneous amplification and testing in early diagnosis of Mycoplasma
      pneumoniae pneumonia and related influencing factors].
AB  - OBJECTIVE: To investigate the value of simultaneous amplification and testing
      (SAT) in the early diagnosis of Mycoplasma pneumoniae pneumonia (MPP) in children
      and related influencing factors. METHODS: A total of 526 children with community
      acquired pneumonia who were hospitalized between December 2016 and December 2017
      were enrolled. Particle agglutination was used to measure serum Mycoplasma
      pneumoniae (MP) antibody (MP-Ab). The value of SAT in the diagnosis of MPP was
      evaluated based on these results. RESULTS: Based on the results of serum MP-Ab
      measurement, 165 children were diagnosed with MPP. MP-SAT had a sensitivity of
      90.9% (150/165), a specificity of 97.9% (368/376), and high accuracy (Youden
      index=0.89) in the diagnosis of MPP, suggesting that there was good consistency
      between these two methods (Kappa=0.90). The diagnostic sensitivity of MP-SAT in
      children with a short course of disease was significantly higher than that in
      children with a long course of disease (P=0.031). The diagnostic sensitivity of
      MP-SAT was significantly higher than that of single serum MP-Ab measurement
      (P=0.018), with poor consistency between these two methods (Kappa=0.039). MP-SAT
      had good consistency with double serum MP-Ab measurement (Kappa=0.91). The
      multivariate logistic regression analysis showed that course of disease (>=7
      days) and out-of-hospital macrolide treatment were the main factors influencing
      the results of MP-SAT (P<0.05). CONCLUSIONS: MP-SAT has high value in the early
      diagnosis of MPP and can effectively cover the shortage of single serum MP-Ab
      test in the acute stage and thus provide help for early clinical diagnosis. MP
      SAT test should be performed in the early stage of the disease (<7 days) and
      before the application of macrolide treatment.

PMID- 30210027
TI  - [Change in the expression of the NLRP3 inflammasome signaling pathway in
      peripheral blood and its significance in children with Mycoplasma pneumoniae
      pneumonia].
AB  - OBJECTIVE: To investigate the expression of the NLRP3 inflammasome signaling
      pathway in peripheral blood and its significance in children with Mycoplasma
      pneumoniae pneumonia (MPP). METHODS: According to the severity, 147 children with
      MPP were divided into mild group with 83 children and severe group with 64
      children. According to the stage of disease, the children were divided into acute
      group with 77 children and recovery stage with 70 children. A total of 50 healthy
      children were enrolled as the control group. Quantitative real-time PCR was used
      to measure the mRNA expression of NLRP3, ASC, and caspase-1. ELISA was used to
      measure the serum levels of interleukin-1beta (IL-1beta) and interleukin-18 (IL
      18). RESULTS: Compared with the control group, the children with MMP had
      significantly higher relative mRNA expression levels of NLRP3, ASC, and caspase-1
      in peripheral blood and serum levels of IL-1beta and IL-18 (P<0.05). Compared
      with the control group, both mild and severe groups had significantly higher
      relative mRNA expression levels of NLRP3, ASC, and caspase-1 in peripheral blood
      and serum levels of IL-1beta and IL-18 (P<0.05). The severe group had
      significantly higher levels of above mentioned parameters than the mild group
      (P<0.05). Both acute group and recovery group had significantly higher relative
      mRNA expression levels of NLRP3, ASC, and caspase-1 in peripheral blood and serum
      levels of IL-1beta and IL-18 than the control group (P<0.05). The acute group had
      significantly higher levels of above mentioned parameters than the recovery group
      (P<0.05). The relative expression level of NLRP3 was positively correlated with
      the relative mRNA expression levels of ASC and caspase-1 and the serum levels of
      IL-1beta and IL-18 (r=0.701, 0.717, 0.676, and 0.645 respectively; P<0.05).
      CONCLUSIONS: The NLRP3 inflammasome signaling pathway might be involved in the
      pathogenesis of MPP in children and is closely associated with the severity and
      course of the disease.

PMID- 30210028
TI  - [A preliminary study of the difference in composition of intestinal
      bifidobacteria between healthy infants and infants with allergic diseases].
AB  - OBJECTIVE: To investigate the association between intestinal bifidobacteria and
      allergic diseases in infants by comparing the composition of intestinal
      bifidobacteria between healthy infants and infants with allergic diseases.
      METHODS: A total of 48 infants were enrolled, and fecal samples were collected on
      days 0, 2, 7, and 15 and at months 1, 6, and 12 after birth. Among these infants,
      22 who experienced allergic diseases before the age of 1 year were enrolled as
      allergic group and 26 healthy infants were enrolled as healthy group.
      Quantitative real-time PCR was used for the qualitative and quantitative analyses
      of Bifidobacterium and 8 species of bifidobacteria in fecal samples. RESULTS:
      There was a difference in the composition of intestinal bifidobacteria between
      the two groups within 1 month after birth: the healthy group showed a reduction
      in bifidobacteria on day 2, while this feature was not observed in the allergic
      group. Compared with the healthy group, the allergic group had a significantly
      lower detection count of Bifidobacterium at month 1 (P<0.05) and a significantly
      lower detection rate of B.breve on day 15 (P<0.05), with delayed colonization of
      B.infantis. CONCLUSIONS: Intestinal bifidobacteria and their composition within 1
      month after birth may be associated with the development of allergic diseases,
      and this period of time may be a critical period for the prevention and treatment
      of allergic diseases in infants.

PMID- 30210029
TI  - [Effect of vitamin D deficiency on cardiac autonomic nerve function in obese pre
      school children].
AB  - OBJECTIVE: To study the effect of vitamin D (VitD) deficiency on cardiac
      autonomic nerve function in obese pre-school children. METHODS: A total of 242
      pre-school children with simple obesity were enrolled, and according to the serum
      25-(OH) VitD level, they were divided into VitD deficiency group (76 children),
      VitD insufficiency group (83 children), and VitD sufficiency group (83 children).
      The three groups were compared in terms of deceleration capacity (DC) of heart
      rate, acceleration capacity (AC) of heart rate, and heart rate variability (HRV).
      The correlations of VitD level with DC, AC, and HRV were analyzed for the VitD
      insufficiency and VitD deficiency groups. RESULTS: The VitD deficiency group had
      the lowest DC, root mean square of successive differences between adjacent RR
      intervals (RMSSD), and low-frequency power (LF) and the highest AC (P<0.05). The
      VitD insufficiency group had significantly lower DC, RMSSD, and LF and
      significantly higher AC compared with the VitD sufficiency group (P<0.05). The
      VitD deficiency group had significantly lower standard deviation of normal-to
      normal RR intervals (SDNN) and high-frequency power (HF) than the VitD
      sufficiency group (P<0.05). In the VitD deficiency group, VitD level was
      positively correlated with DC, SDNN, standard deviation of average normal-to
      normal RR intervals, RMSSD , LF, and HF and was negatively correlated with AC
      (P<0.05). In the VitD insufficiency group, VitD level was negatively correlated
      with AC (P<0.05). CONCLUSIONS: Obese pre-school children with VitD insufficiency
      or deficiency have cardiac autonomic dysfunction, and cardiac vagal tone
      decreases with the reduction in VitD level.

PMID- 30210030
TI  - [Clinical and genetic analysis of an infant with progressive familial
      intrahepatic cholestasis type II].
AB  - Progressive familial intrahepatic cholestasis type II (PFIC-2) is an autosomal
      recessive disorder caused by biallelic variants of ABCB11 gene. This paper
      reports the clinical and laboratory features of a pediatric patient with PFIC-2.
      The patient was a 2.4-month-old male infant with jaundice and hepatomegaly as the
      main clinical manifestations. The serum levels of total bilirubin, direct
      bilirubin and total bile acids were increased, while the serum gamma-glutamyl
      transpeptidase (GGT) level was normal. Next generation sequencing revealed two
      missense variants, c.1493T>C(p.Ile498Thr) and c.1502T>G(p.Val501Gly), in the
      ABCB11 gene of the patient, which were inherited from his father and mother,
      respectively. The latter was a novel variant which was predicted to be pathogenic
      by using a variety of bioinformatic tools, and the affected p.Val501 residue was
      highly conserved in 112 homologous peptides.

PMID- 30210031
TI  - [Clinical features and FKRP mutations of congenital muscular dystrophy 1C].
AB  - Congenital muscular dystrophy type 1C (MDC1C) is caused by the homozygous or
      compound heterozygous mutations of the FKRP gene. This article reported the
      clinical and mutation features of a child with MDC1C. The boy aged 8 months
      visited the hospital due to delayed development. As for clinical manifestations,
      the boy could not turn over or sit stably by himself, and there was a significant
      reduction in muscle tension; biceps reflex in both upper extremities and patellar
      tendon reflex and Achilles tendon reflex in both lower extremities could not be
      induced. The boy also had a stereotyped facial expression and strabismus. Gene
      detection revealed c.350C>G and c.1303C>T compound heterozygous mutations in the
      FKRP gene. The c.350C>G mutation came from the mother and had been reported as a
      pathogenic missense mutation. The c.1303C>T mutation came from the father and was
      a new missense mutation, and a bioinformatics analysis showed that it might be a
      pathogenic mutation. The boy was diagnosed with MDC1C with reference to the
      clinical features of hypotonia and motor developmental delay and FKRP gene
      mutation sequencing.

PMID- 30210032
TI  - [Effects of Yinzhihuang oral liquid and Lonicera japonica extract on hemolysis
      and hyperbilirubinemia in rats with glucose-6-phosphate dehydrogenase
      deficiency].
AB  - OBJECTIVE: To investigate the effects of different doses of Yinzhihuang oral
      liquid and different concentrations of Lonicera japonica extract on hemolysis and
      hyperbilirubinemia in rats with glucose-6-phosphate dehydrogenase (G6PD)
      deficiency. METHODS: Male Wistar rats were randomly divided into 10 groups (n=10
      each): normal control group (untreated), negative control group (saline-treated),
      positive control group (primaquine-treated), low-, medium- and high-dose
      Yinzhihuang oral liquid groups (13.4, 26.8, and 53.6 mL/kg, respectively), and
      low-, medium-, high-, and very-high-concentration Lonicera japonica groups (6.7
      mL/kg administered, containing 8, 40, 80, and 160 mg/mL Lonicera japonica
      extract, respectively). A rat model of acetylphenylhydrazine-induced G6PD
      deficiency was established in all groups except the normal control group, as
      confirmed by the morphological changes in erythrocytes observed using Wright's
      stain. After treatment, routine blood and biochemical tests were conducted to
      measure hemolytic indices, as well as changes in total and indirect bilirubin
      levels. RESULTS: Rats with G6PD deficiency demonstrated irregular erythrocytes
      with a lighter-staining center. In the positive control group, the red blood cell
      count decreased, while the free hemoglobin count and the reticulocyte percentage
      increased, as compared with before treatment (P<0.05); in all the Yinzhihuang
      oral liquid groups and Lonicera japonica extract groups, all the above indices
      except reticulocyte percentage returned to the levels before treatment (P<0.05).
      Compared with the positive control group, all the Yinzhihuang oral liquid groups
      had significantly reduced total and indirect bilirubin levels (P<0.05), and all
      the Lonicera japonica group had significantly reduced indirect bilirubin levels
      (P<0.05). However, the total bilirubin level was significantly higher in the
      Lonicera japonica groups than in the Yinzhihuang oral liquid groups (P<0.05). The
      low-dose Yinzhihuang oral liquid group demonstrated a significantly greater
      decrease in total bilirubin level than the medium- and high-dose Yinzhihuang oral
      liquid group (P<0.05). CONCLUSIONS: Administration of high-dose Yinzhihuang oral
      liquid and different concentrations of Lonicera Japonica extract do not cause
      hemolysis in rats with G6PD deficiency. Yinzhihuang oral liquid is more effective
      in treating hyperbilirubinemia than Lonicera Japonica extract. However, the
      efficacy of Yinzhihuang oral liquid may not be dose-dependent.

PMID- 30210033
TI  - [Research advances in pathogenesis of attention deficit hyperactivity disorder].
AB  - Both of genetic and environmental factors play important roles in the
      pathogenesis of attention deficit hyperactivity disorder (ADHD), and genetic
      factors can increase the susceptibility of individuals to environmental risk
      factors. There are extensive and various structural and functional abnormalities
      of the brain in patients with ADHD. Given the close functional relationship
      between brain areas, exploration has also been expanded to the dysfunction of
      brain network in recent years. As for the biochemical mechanism underlying ADHD,
      monoamine neurotransmitters are still most valued, and abnormalities of brain
      derived neurotrophic factors and glutamic acid/gamma-aminobutyric acid imbalance
      may also be present. Due to the abnormal neuroendocrine function and connectivity
      between brain areas caused by the synergistic effect of genetic and environmental
      factors, the prefrontal cortex loses control of the lower brain areas, so that
      the basal ganglia and amygdala affect normal behavioral and emotional reactions.
      Dysfunction of the endocrine axes may further aggravate neuroendocrine disorder.
      The above process may eventually lead to changes in brain structure and function,
      which may be associated with the development of ADHD. However, considering the
      heterogeneity of ADHD, its pathological process may not be the same, and the
      exact mechanism needs to be further clarified.

PMID- 30210034
TI  - [Progress in immunotherapy for children with anti-N-methyl-D-aspartate receptor
      encephalitis].
AB  - Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is an autoimmune
      encephalitis that was reported in recent years. At present, there remains no
      unified treatment regimen for the children and adolescents with this disease
      around the world. Immunotherapy is still the preferred way of treatment, mainly
      including first-line immunotherapy, second-line immunotherapy, and long-term
      immunotherapy. In recent years, some researchers have tried new
      immunosuppressants or modified immunotherapy regimens to improve the treatment
      outcome of the patients. This article summarizes related immunotherapy regimens,
      as well as the future direction of research on immunotherapy for anti-NMDAR
      encephalitis.

PMID- 30210035
TI  - Prevalence of papillary thyroid cancer in subacute thyroiditis patients may be
      higher than it is presumed: retrospective analysis of 137 patients.
AB  - Background The association of subacute thyroiditis (SAT) and papillary thyroid
      carcinoma is a rare finding. In this study, we aimed to investigate the
      prevalence of differentiated thyroid cancer in a cohort of patients followed with
      the diagnosis of SAT. Patients and methods We retrospectively screened medical
      records of Endocrinology and Metabolism outpatient clinic in the past 20 years
      for patients with SAT. Patients with nodules and suspicious ultrasonography
      findings who underwent fine needle aspiration biopsy (FNAB) and operated due to
      malignancy risk were identified. Results We identified 137 (100 females, 37
      males) patients with reliable records to confirm the diagnosis of SAT. The mean
      age of female patients was 41.1 +/- 9.1 (range, 20-64) and of male patients was
      43.0 +/- 9.3 (range, 20-65). One or more FNAB was performed in 23 of the patients
      (16.8%) at the beginning and/or during the follow-up period when needed. Seven
      patients with suspicious FNAB findings were operated, and histopathological
      examination of the nodules confirmed the diagnosis of papillary thyroid carcinoma
      in 6 patients (4.4%). Conclusions Our observations suggesting a relatively higher
      prevalence of thyroid cancer in a small series of SAT patients warrant further
      studies to identify the real frequency of differentiated thyroid cancer and its
      association with inflammatory pathogenesis of SAT. This finding is compatible
      with the trend of increased thyroid cancer incidence all over the world. A repeat
      ultrasonography after resolution of clinical and inflammatory findings, and FNAB
      should be recommended to all patients with suspicious nodules.

PMID- 30210036
TI  - Epidemiology of oral mucosal lesions in Slovenia.
AB  - Background Among the diseases of oral mucosa, malignant tumors are the most
      dangerous, but not the most common lesions that might appear in the oral cavity.
      Since most of the studies are focused on the detection of cancer in the oral
      cavity, we were interested in detecting the frequency of benign changes of the
      oral mucosa in Slovene population. Oral mucosal lesions are important pointer of
      oral health and quality of life, especially in elderly. The prevalence of oral
      mucosal lesions, together with information on the risk habits associated with
      oral health, such as tobacco and alcohol use, can help in planning future oral
      health studies and screening programs. Patients and methods Survey upon oral
      mucosal lesions was conducted during the national project for oral cancer
      screening in spring 2017 in the Slovenia in which more than 50% of dentists
      participated and 2395 patients (904 men and 1491 women) were included. Results
      Clinical examination, which was conducted according to the WHO standards revealed
      that 645 patients (27%) had oral mucosal lesions. The ten most common oral
      lesions detected were fibroma, gingivitis, Fordyce spots, white coated tongue,
      cheek biting, linea alba, denture stomatitis, geographic tongue, recurrent
      aphthous ulcerations and lichen planus. Conclusions Overall, these
      epidemiological data suggest need for specific health policies for prevention,
      diagnosis and treatment of oral mucosal lesions.

PMID- 30210037
TI  - Long-term survival of locally advanced stage III non-small cell lung cancer
      patients treated with chemoradiotherapy and perspectives for the treatment with
      immunotherapy.
AB  - Background Standard treatment for patients with inoperable locally advanced non
      small cell lung cancer (NSCLC) is concurrent chemoradiotherapy (CCRT). Five-year
      overall survival rates range between 15 and 25%, while long term survival data
      are rarely reported. Patients and methods A total of 102 patients with stage III
      NSCLC treated between September 2005 and November 2010 with induction
      chemotherapy and CCRT were included in this long term survival analysis. All
      patients were tested for PD-L1 status and expression of PD-L1 was correlated with
      overall survival (OS), progression free survival (PFS) and toxicities. Results
      The median OS of all patients was 24.8 months (95% CI 18.7 to 31.0) with 10 year
      survival rate of 11.2%. The median OS of patients with PD-L1 expression was 12.1
      months (95% CI 0.1 to 26.2), while in patients with negative or unknown PD-L1
      status was significantly longer, 25.2 months (95% CI 18.9 to 31.6), p = 0.005.
      The median PFS of all patients was 16.4 months (95% CI 13.0 to 19.9). PFS of
      patients with PD-L1 expression was 10.1 months (95% CI 0.1 to 20.4) and in
      patients with negative or unknown PD-L1 status was 17.9 months (95% CI 14.2 to
      21.7), p = 0.003. Conclusions 10-year overall survival of stage III NSCLC
      patients after CCRT is 11.2%. PFS and OS differ with regard to PD-L1 status and
      are significantly shorter for patients with PD-L1 expression. New treatment with
      check-point inhibitors combined with RT therefore seems reasonable strategy to
      improve these results.

PMID- 30210038
TI  - Singular value decomposition analysis of back projection operator of maximum
      likelihood expectation maximization PET image reconstruction.
AB  - Background In emission tomography maximum likelihood expectation maximization
      reconstruction technique has replaced the analytical approaches in several
      applications. The most important drawback of this iterative method is its linear
      rate of convergence and the corresponding computational burden. Therefore,
      simplifications are usually required in the Monte Carlo simulation of the back
      projection step. In order to overcome these problems, a reconstruction code has
      been developed with graphical processing unit based Monte Carlo engine which
      enabled full physical modelling in the back projection. Materials and methods
      Code performance was evaluated with simulations on two geometries. One is a
      sophisticated scanner geometry which consists of a dodecagon with inscribed
      circle radius of 8.7 cm, packed on each side with an array of 39 * 81 LYSO
      detector pixels of 1.17 mm sided squares, similar to a Mediso nanoScan PET/CT
      scanner. The other, simplified geometry contains a 38,4mm long interval as a
      voxel space, detector pixels are assigned in two parallel sections each
      containing 81 crystals of a size 1.17*1.17 mm. Results We have demonstrated that
      full Monte Carlo modelling in the back projection step leads to material
      dependent inhomogeneities in the reconstructed image. The reasons behind this
      apparently anomalous behaviour was analysed in the simplified system by means of
      singular value decomposition and explained by different speed of convergence.
      Conclusions To still take advantage of the higher noise stability of the full
      physical modelling, a new filtering technique is proposed for convergence
      acceleration. Some theoretical considerations for the practical implementation
      and for further development are also presented.

PMID- 30210039
TI  - Prevalence of BRAF, NRAS and c-KIT mutations in Slovenian patients with advanced
      melanoma.
AB  - Background BRAF, NRAS and c-KIT mutations are characteristics of tumour tissues
      that influence on treatment decisions in metastatic melanoma patients. Mutation
      frequency and their correlation with histological characteristics in Slovenian
      population have not been investigated yet. Patients and methods In our
      retrospective analysis we analysed mutational status of BRAF, NRAS and c-KIT in
      230 pathological samples of patients who were intended to be treated with
      systemic therapy due to metastatic disease at the Institute of Oncology Ljubljana
      between 2013 and 2016. We collected also histological characteristics of primary
      tumours and clinical data of patients and correlated them with mutational status
      of tumour samples. Results The study population consisted of 230 patients with a
      mean age 59 years (range 25-85). 141 (61.3%) were males and 89 (38.7%) females.
      BRAF mutations were identified in 129 (56.1%), NRAS in 31 (13.5%) and c-KIT in 3
      (1.3%) tissue samples. Among the 129 patients with BRAF mutations, 114 (88.4%)
      patients had V600E mutation and 15 (11.6%) had V600K mutation. Patients with BRAF
      mutations tended to be younger at diagnosis (52 vs. 59 years, p < 0.05), patients
      with NRAS mutations older (61 vs. 55 years, p < 0.05). Number of c-KIT mutations
      were too low for any statistical correlation, but there was one out of 3 melanoma
      located in mucus membranes. Conclusions The analysis detected high rate of BRAF
      mutations, low NRAS mutations and low c-KIT mutations compared to previously
      published studies in Europe and North America. One of the main reasons for this
      observation is specific characteristics of study population.

PMID- 30210041
TI  - Three-dimensional ultrasound evaluation of tongue posture and its impact on
      articulation disorders in preschool children with anterior open bite.
AB  - Background Tongue posture plays an important role in the etiology of anterior
      open bite (AOB) and articulation disorders, and is crucial for AOB treatment
      planning and posttreatment stability. Clinical assessment of tongue posture in
      children is unreliable due to anatomical limitations. The aim of the study was to
      present functional diagnostics using three-dimensional ultrasound (3DUS)
      assessment of resting tongue posture in comparison to clinical assessment, and
      the associations between the improper tongue posture, otorhinolaryngological
      characteristics, and articulation disorders in preschool children with AOB.
      Patients and methods A cross-sectional study included 446 children, aged 3-7
      years, 236 boys and 210 girls, examined by an orthodontist to detect the
      prevalence of AOB. The AOB was present in 32 children. The control group
      consisted of 43 children randomly selected from the participants with
      normocclusion. An orthodontist, an ear, nose and throat (ENT) specialist and a
      speech therapist assessed orofacial and ENT conditions, oral habits, and
      articulation disorders in the AOB group and control group. Tongue posture was
      also assessed by an experienced radiologist, using 3DUS. The 3DUS assessment of
      tongue posture was compared to the clinical assessment of orthodontist and ENT
      specialist. Results The prevalence of AOB was 7.2%. The AOB group and the control
      group significantly differed regarding improper tongue posture (p < 0.001), and
      articulation disorders (p < 0.001). In children without articulation disorders
      from both groups, the improper tongue posture occured less frequently than in
      children with articulation disorders (p < 0.001). After age adjustment, a
      statistical regression model showed that the children with the improper tongue
      posture had higher odds ratios for the presence of AOB (OR 14.63; p < 0.001) than
      the others. When articulation disorders were included in the model, these odds
      ratios for the AOB became insignificant (p = 0.177). There was a strong
      association between the improper tongue posture and articulation disorders (p =
      0.002). The 3DUS detected the highest number of children with improper resting
      tongue posture, though there was no significant difference between the 3DUS and
      clinical assessments done by orthodontist and ENT specialist. Conclusions The
      3DUS has proved to be an objective, non-invasive, radiation free method for the
      assessment of tongue posture and could become an important tool in functional
      diagnostics and early rehabilitation in preschool children with speech
      irregularities and irregular tongue posture and malocclusion in order to enable
      optimal conditions for articulation development.

PMID- 30210040
TI  - Induction chemotherapy, chemoradiotherapy and consolidation chemotherapy in
      preoperative treatment of rectal cancer - long-term results of phase II OIGIT-01
      Trial.
AB  - Background The purpose of the study was to improve treatment efficacy for locally
      advanced rectal cancer (LARC) by shifting half of adjuvant chemotherapy
      preoperatively to one induction and two consolidation cycles. Patients and
      methods Between October 2011 and April 2013, 66 patients with LARC were treated
      with one induction chemotherapy cycle followed by chemoradiotherapy (CRT), two
      consolidation cycles, surgery and three adjuvant capecitabine cycles. Radiation
      doses were 50.4 Gy for T2-3 and 54 Gy for T4 tumours in 1.8 Gy daily fraction.
      The doses of concomitant and neo/adjuvant capecitabine were 825 mg/m2/12h and
      1250mg/m2/12h, respectively. The primary endpoint was pathologic complete
      response (pCR). Results Forty-three (65.1%) patients were treated according to
      protocol. The compliance rates for induction, consolidation, and adjuvant
      chemotherapy were 98.5%, 93.8% and 87.3%, respectively. CRT was completed by
      65/66 patients, with G >= 3 non-hematologic toxicity at 13.6%. The rate of pCR
      (17.5%) was not increased, but N and the total-down staging rates were 77.7% and
      79.3%, respectively. In a median follow-up of 55 months, we recorded one local
      relapse (LR) (1.6%). The 5-year disease-free survival (DFS) and overall survival
      (OS) rates were 64.0% (95% CI 63.89-64.11) and 69.5% (95% CI 69.39-69.61),
      respectively. Conclusions In LARC preoperative treatment intensification with
      capecitabine before and after radiotherapy is well tolerated, with a high
      compliance rate and acceptable toxicity. Though it does not improve the local
      effect, it achieves a high LR rate, DFS, and OS.

PMID- 30210043
TI  - Dynamics of CT visible pleural effusion in patients with pulmonary infarction.
AB  - Background Pleural effusion remains largely unexplored in patients with pulmonary
      embolism and concurrent pulmonary infarction. The aim of the study was to
      investigate the relationship between the size of pulmonary infarction and pleural
      effusion as well as the time course of pleural effusion in patients with
      pulmonary infarction. Patients and methods Data from 103 patients with pulmonary
      infarction was retrospectively analysed along with patient comorbidities, size of
      pulmonary infarction, presence and size of pleural effusion with the time between
      the onset of clinical symptoms of pulmonary infarction and CT study. Results
      Assessment of possible correlations between the size of pulmonary infarction and
      age revealed a significant negative correlation. There was a highly significant
      difference (p = 0.005) in the mean size of pulmonary infarction in patients with
      effusion (34.5 cm3) compared to those without it (14.3 cm3), but the size of the
      effusion had no correlation with the size of pulmonary infarction. The size of
      the effusion peaked between 4th-5th day after the onset of clinical symptoms of
      pulmonary infarction. In the first 5 days after the onset of clinical symptoms of
      pulmonary infarction a significant correlation was found between the size of the
      effusion and time with approximation of 1.3 mm/12 h. Conclusions The data shows
      that patients with a pleural effusion are more likely to have a larger pulmonary
      infarction than those without it. If present, the effusion can be expected to
      increase in a relatively slow linear fashion in the first 5 days after the onset
      of clinical symptoms of pulmonary infarction.

PMID- 30210042
TI  - Percutaneous parametrial dose escalation in women with advanced cervical cancer:
      feasibility and efficacy in relation to long-term quality of life.
AB  - Background We analyzed long-term quality of life (QoL) and prognostic factors for
      QoL as well as clinical outcome in patients with advanced cervical cancer (ACC)
      treated with primary radiochemotherapy (RChT) consisting of external beam
      radiotherapy (EBRT) with or without sequential or simultaneous integrated boost
      (SIB) to the parametria, intracavitary brachytherapy and concomitant chemotherapy
      (ChT). Patients and methods Eighty-three women were treated with primary RChT
      between 2008 and 2014. Survival of all patients was calculated and prognostic
      factors for survival were assessed in univariate and multivariate analysis. In 31
      patients QoL was assessed in median 3 years (range 2-8 years) after treatment.
      QoL was compared to published normative data and the influence of age, tumour
      stage, treatment and observed acute toxicities was analyzed. Results Thirty-six
      patients (43.4%) died, 18 (21.7%) had a local recurrence and 24 (28.9%) had a
      distant progression. Parametrial boost (p = 0.027) and ChT (p = 0.041) were
      independent prognostic factors for overall survival in multivariate analysis.
      Specifically, a parametrial equivalent doses in 2-Gy fractions (EQD2) > 50 Gy was
      associated with an improved overall survival (OS) (p = 0.020), but an EQD2 > 53
      Gy did not further improve OS (p = 0.194). Tumour size was the only independent
      prognostic factor for local control (p = 0.034). Lymph node status (p = 0.038)
      and distant metastases other than in paraaortic lymph nodes (p = 0.002) were
      independent prognostic factors for distant progressionfree survival. QoL was
      generally inferior to the reference population. Age only correlated with
      menopausal symptoms (p = 0.003). The degree of acute gastrointestinal (p = 0.038)
      and genitourinary (p = 0.041) toxicities correlated with the extent of chronic
      symptom experience. Sexual/vaginal functioning was reduced in patients with
      larger tumours (p = 0.012). Parametrial EQD2 > 53 Gy correlated with reduced
      sexual/vaginal functioning (p = 0.009) and increased sexual worry (p = 0.009).
      Whether parametrial dose escalation was achieved by sequential boost or SIB, did
      not affect survival or QoL. Conclusions Primary RChT is an effective treatment,
      but long-term QoL is reduced. The degree of acute side effects of RChT correlates
      with the extent of chronic symptoms. Patients benefit from parametrial SIB or
      sequential boost, but an EQD2 > 53 Gy does not further improve survival and
      negatively affects QoL.

PMID- 30210044
TI  - A proposal for a quality control protocol in breast CT with synchrotron
      radiation.
AB  - Background The SYRMA-3D collaboration is setting up the first clinical trial of
      phase-contrast breast CT with synchrotron radiation at the Elettra synchrotron
      facility in Trieste, Italy. In this communication, a quality control protocol for
      breast CT is proposed, and a first test of image quality measurements is
      performed by means of a custom-made radiographic phantom. Materials and methods A
      set of projections is acquired and used to perform a CT reconstruction of two
      selected portions of the phantom. Such portions contain a uniform layer of water
      and a set of radiographic inserts, respectively. Together, they allow to perform
      several image quality measurements, namely CT number linearity, reconstruction
      accuracy, uniformity, noise, and low contrast resolution. All measurements are
      repeated at different beam energies in the range of interest, and at two
      different dose values. Results Measurements show a good linearity in the soft
      tissue range, paired to a high accuracy of the CT number reconstruction.
      Uniformity and noise measurements show that reconstruction inhomogeneities are
      bound to a few percent of the average pixel values. However, low contrast
      detectability is limited to the higher portion of the explored energy range.
      Conclusions The results of the measurements are satisfactory in terms of their
      quality, feasibility and reproducibility. With minimal modifications, the phantom
      is promising to allow a set of image quality measurements to be used in the
      upcoming clinical trial.

PMID- 30210045
TI  - Is postmastectomy radiotherapy really needed in breast cancer patients with many
      positive axillary lymph nodes?
AB  - Background Postmastectomy radiotherapy (PMRT) improves survival by eliminating
      potential occult lesions in the chest wall and lymphatic drainage area. Meta
      analysis has shown that PMRT reduces mortality and local recurrence of patients
      with node positive breast cancer, but there is no specific data about the
      effectiveness of PMRT in a subgroup of patients with a high number of positive
      axillary lymph nodes (PALN). The aim of the study was to analyse the impact of
      the number of PALN on local and distant metastasis occurrence, overall survival
      (OS) and distant metastases free survival (DMFS) in patients treated with PMRT.
      Patients and methods We reviewed medical records of 129 consecutive breast cancer
      patients with PALN, treated at Institute of Oncology Ljubljana with PMRT between
      January 2003 and December 2004. We grouped patients according to the number of
      PALN as follows: Group 1 (less than 15 PALN) and Group 2 with more than 15 PALN.
      All patients received adjuvant systemic therapy according to the clinical
      guidelines. We analysed number of locoregional (LR) recurrences, distant
      metastasis, overall survival (OS), progression free survival (PFS) and DMFS.
      Results After the median follow-up time of 11.5 years, the Kaplan-Meier survival
      analysis of PALN showed significantly shorter OS (p = 0.006), shorter PFS (p =
      0.002) and shorter DMFS (p < 0.001) in the group of > 15 PALN. Only one LR was
      found in the group of patients with more than 15 PALN. In multivariate analysis
      more than 15 PALN and treatment with anthracycline chemotherapy statistically
      significantly influenced OS and DMFS. For PFS presence of more than 15 PALN were
      the only independent factor of shorter survival. Conclusions Patients with more
      than 15 PALN have shorter DMFS, PFS and OS as compared to patients with less than
      15 PALN, though they receive the same LR treatment. More studies with higher
      number of patients included are needed to further evaluate our findings.

PMID- 30210046
TI  - Evaluation of two-dimensional dose distributions for pre-treatment patient
      specific IMRT dosimetry.
AB  - Background The accuracy of dose calculation is crucial for success of the
      radiotherapy treatment. One of the methods that represent the current standard
      for patient-specific dosimetry is the evaluation of dose distributions measured
      with an ionization chamber array inside a homogeneous phantom using gamma method.
      Nevertheless, this method does not replicate the realistic conditions present
      when a patient is undergoing therapy. Therefore, to more accurately evaluate the
      treatment planning system (TPS) capabilities, gamma passing rates were examined
      for beams of different complexity passing through inhomogeneous phantoms.
      Materials and methods The research was performed using Siemens Oncor Expression
      linear accelerator, Siemens Somatom Open CT simulator and Elekta Monaco TPS. A 2D
      detector array was used to evaluate dose distribution accuracy in homogeneous,
      semi-anthropomorphic and anthropomorphic phantoms. Validation was based on gamma
      analysis with 3%/3mm and 2%/2mm criteria, respectively. Results Passing rates of
      the complex dose distributions degrade depending on the thickness of non-water
      equivalent material. They also depend on dose reporting mode used. It is observed
      that the passing rate decreases with plan complexity. Comparison of the data for
      all set-ups of semi-anthropomorphic and anthropomorphic phantoms shows that
      passing rates are higher in the anthropomorphic phantom. Conclusions Presented
      results raise a question of possible limits of dose distribution verification in
      assessment of plan delivery quality. Consequently, good results obtained using
      standard patient specific dosimetry methodology do not guarantee the accuracy of
      delivered dose distribution in real clinical cases.

PMID- 30210047
TI  - Pharmacogenomic markers of glucocorticoid response in the initial phase of
      remission induction therapy in childhood acute lymphoblastic leukemia.
AB  - Background Response to glucocorticoid (GC) monotherapy in the initial phase of
      remission induction treatment in childhood acute lymphoblastic leukemia (ALL)
      represents important biomarker of prognosis and outcome. We aimed to study
      variants in several pharmacogenes (NR3C1, GSTs and ABCB1) that could contribute
      to improvement of GC response through personalization of GC therapy. Methods
      Retrospective study enrolling 122 ALL patients was carried out to analyze
      variants of NR3C1 (rs33389, rs33388 and rs6198), GSTT1 (null genotype), GSTM1
      (null genotype), GSTP1 (rs1695 and rs1138272) and ABCB1 (rs1128503, rs2032582 and
      rs1045642) genes using PCR-based methodology. The marker of GC response was blast
      count per microliter of peripheral blood on treatment day 8. We carried out
      analysis in which cut-off value for GC response was 1000 (according to Berlin
      Frankfurt-Munster [BFM] protocol), as well as 100 or 0 blasts per microliter.
      Results Carriers of rare NR3C1 rs6198 GG genotype were more likely to have blast
      count over 1000, than the non-carriers (p = 0.030). NR3C1 CAA (rs33389-rs33388
      rs6198) haplotype was associated with blast number below 1000 (p = 0.030). GSTP1
      GC haplotype carriers were more likely to have blast number below 1000 (p =
      0.036), below 100 (p = 0.028) and to be blast negative (p = 0.054), while GSTP1
      GT haplotype and rs1138272 T allele carriers were more likely to be blasts
      positive (p = 0.034 and p = 0.024, respectively). ABCB1 CGT (rs1128503-rs2032582
      rs1045642) haplotype carriers were more likely to be blast positive (p = 0.018).
      Conclusions Our results have shown that NR3C1 rs6198 variant and GSTP1 rs1695
      rs1138272 haplotype are the most promising pharmacogenomic markers of GC response
      in ALL patients.

PMID- 30210050
TI  - The Option Value of Innovative Treatments for Metastatic Melanoma.
AB  - Background Treatment options in oncology have increased in recent years due to
      the quick pace of innovation. In the cancer care landscape, therapies that enable
      patients to live to the next innovation have additional value, "option value,"
      from the benefit of surviving to the next innovation. In such disease areas,
      providers and payers should consider this value when gauging the value of new
      therapies. The purpose of this study is to develop a model to estimate the
      additional survival patients attain from a therapy that allows them to live to
      benefit from further advances in care, and to apply the model to immunotherapy
      for metastatic melanoma. Methods The benefit of a therapy extends beyond
      immediate tumor control; it can also allow patients to live to benefit from
      further advances in care. This is a therapy's option value. Using data from the
      SEER cancer registry and clinical trial publications, we developed a model to
      estimate option value and applied it to ipilimumab, the first immune checkpoint
      modulator used to treat metastatic melanoma. Because ipilimumab extends survival,
      select patients benefited from survival extension to live to benefit from the
      introduction of PD-1 inhibitors (i.e. pembrolizumab and nivolumab). We calculated
      the option value of ipilimumab in terms of additional life-months patients gained
      by living to become potential candidates for PD-1 inhibitors, discounting at 3%
      per year. Results Patients taking ipilimumab as a second-line therapy for
      metastatic melanoma gained 10.5 months compared to patients taking the prior
      standard of care. Patients diagnosed in 2011, 2012, and 2013 gained an additional
      1.6, 2.8, and 5.1 months of life expectancy, respectively, by living to see the
      introduction of PD-1 inhibitors. This equates to an option value of 15%, 27%, and
      49%, respectively, of the conventionally calculated survival gain from
      ipilimumab. Ipilimumab had greater option value for patients diagnosed in later
      years who were more likely to live to the introduction of PD-1 inhibitors.
      Conclusions Therapies that enable patients to see further advances in care have
      option value. Option value is particularly important to patients with disease
      areas undergoing rapid innovation.

PMID- 30210048
TI  - Breast size impact on adjuvant radiotherapy adverse effects and dose parameters
      in treatment planning.
AB  - Background Breast radiotherapy is an established adjuvant treatment after breast
      conserving surgery. One of the important individual factors affecting the final
      cosmetic outcome after radiation is breast size. The purpose of this review is to
      summarise the clinical toxicity profile of adjuvant radiotherapy in women with
      breasts of various sizes, and to evaluate the treatment planning studies
      comparing target coverage and dose to thoracic organs at risk in relation to
      breast size. Conclusions Inhomogeneity and excessive radiation dose (hot spots)
      in the planning of target volume as well as large volume of the breast per se,
      all contribute to a higher rate of acute adverse events and suboptimal final
      cosmetic outcome in adjuvant breast cancer radiotherapy, regardless of the
      fractionation schedule. Improved homogeneity leads to a lower rate of >= grade 2
      toxicity and can be achieved with three-dimensional conformal or modulated
      radiotherapy techniques. There may be an association between body habitus (higher
      body mass index, bigger breast size, pendulous breast, and large chest wall
      separation) and a higher mean dose to the ipsilateral lung and whole heart. A
      combination of the technical innovations (i.e. the breath-hold technique, prone
      position with or without holding breath, lateral decubitus position, and
      thermoplastic bra), dose prescription (i.e. moderate hypofractionation), and
      irradiated volume (i.e. partial breast irradiation) should be tailored to every
      single patient in clinical practice to mitigate the risk of radiation adverse
      effects.

PMID- 30210051
TI  - The Value of the Health and Retirement Study for Health Economics Research.
AB  - We assess the value of the Health and Retirement Study (HRS) for research in
      health economics by conducting a survey of leading health economists. We analyze
      the survey responses to provide an assessment of the strengths of the HRS for
      this kind of research, as well as the obstacles that prevent it from being used
      more widely. We offer some suggestions as to how these obstacles might be
      overcome through changes to the survey and actions to increase survey awareness
      and access.

PMID- 30210049
TI  - Primary debulking surgery versus primary neoadjuvant chemotherapy for high grade
      advanced stage ovarian cancer: comparison of survivals.
AB  - Background The aim of the study was to analyze the overall survival (OS) and
      progression free survival (PFS) of patients with high grade and advanced stage
      epithelial ovarian cancer (EOC) with at least 60 months of follow-up treated in a
      single gynecologic oncology institute. We compared primary debulking surgery
      (PDS) versus neoadjuvant chemotherapy plus interval debulking surgery (NACT +
      IDS) stratifying data based on residual disease with the intent to identify the
      rationale for therapeutic option decision and the role of laparoscopic evaluation
      of resectability for that intention. Patients and methods This is observational
      retrospective study on consecutive patients with diagnosis of high grade and
      International Federation of Gynecology and Obstetrics (FIGO) stage III/IV EOC
      referred to our center between January 2008 and May 2012. We selected only
      patients with a follow-up of at least 60 months. Primary endpoint was to compare
      PDS versus NACT + IDS in term of progression free survival (PFS) and overall
      survival (OS). Secondary endpoints were PFS and OS stratifying data according to
      residual disease after surgery in patients receiving PDS versus NACT + IDS.
      Finally, through Cox hazards models, we tested the prognostic value of different
      variables (patient age at diagnosis, residual disease after debulking, American
      Society of Anesthesiologists (ASA) stage, number of adjuvant-chemotherapy cycles)
      for predicting OS. Results A total number of 157 patients were included in data
      analysis. Comparing PDS arm (108 patients) and NACT + IDS arm (49 patients) we
      found no significant differences in term of OS (41.3 versus 34.5 months,
      respectively) and PFS (17.3 versus 18.3 months, respectively). According to
      residual disease we found no significant differences in term of OS between NACT +
      IDS patients with residual disease = 0 and PDS patients with residual disease = 0
      or residual disease = 1, as well as no significant differences in PFS were found
      comparing NACT + IDS patients with residual disease = 0 and PDS patients with
      residual disease = 0; contrarily, median PFS resulted significantly lower in PDS
      patients receiving optimal debulking (residual disease = 1) in comparison to NACT
      + IDS patients receiving complete debulking (residual disease = 0). PDS arm was
      affected by a significant higher rate of severe post-operative complications
      (grade 3 and 4). Diagnostic laparoscopy before surgery was significantly
      associated with complete debulking. Conclusions We confirm previous findings
      concerning the non-superiority of NACT + IDS compared to PDS for the treatment of
      EOC, even if NACT + IDS treatment was associated with significant lower rate of
      post-operative complications. On the other hand, selecting patients for NACT +
      IDS, based on laparoscopic evaluation of resectabilty prolongs the PFS and does
      not worse the OS compared to the patients not completely debulked with PDS.

PMID- 30210052
TI  - Disability Measurement in the Health and Retirement Study.
AB  - The Health and Retirement Study (HRS) has provided extensive and detailed
      national data on disability since it began in 1992, and has been used extensively
      in studies of disability trends and trajectories. We summarize conceptual
      frameworks used to characterize disability and review the HRS measures of
      functioning, work disability, and employer accommodations. HRS survey questions
      have experienced changes in wording, skip logic, or other design features over
      the life of the study, and we comment on the analytic challenges posed by those
      changes. Among our conclusions are (1) work disability and benefit eligibility
      are important concepts that should be considered for redesign to better reflect
      current concepts and policy issues; (2) methodological studies of changes in
      wording or skip logic should be undertaken; and (3) minor additions to survey
      content in areas such as temporal reference periods or changes in social
      participation activities would improve measurement.

PMID- 30210053
TI  - Characterization of the cholesterol efflux of apolipoprotein E-containing high
      density lipoprotein in THP-1 cells.
AB  - High-density lipoprotein (HDL), also known as antiatherogenic lipoprotein,
      consists of heterogeneous particles in terms of size, density and composition,
      suggesting differences among HDL subclasses in characteristics and functions. We
      investigated the role of apolipoprotein E (apoE)-containing HDL, a minor HDL
      subclass, in the cholesterol efflux capacity (CEC) of HDL, which is its
      predominant atheroprotective function. The CEC of apoE-containing HDL was similar
      to that of apoE-deficient HDL, but the former exhibited a greater rate increase
      (1.48-fold) compared to that of the latter (1.10-fold) by the stimulation of THP
      1 macrophages with the Liver X Receptor (LXR) agonist. No difference in CEC was
      observed without the LXR agonist between apoA-I, the main apolipoprotein in HDL,
      and apoE, whereas the increase in CEC in response to treatment with the LXR
      agonist was greater for apoA-I (4.25-fold) than for apoE (2.22-fold).
      Furthermore, the increase in the CEC of apoE-containing HDL induced by the LXR
      agonist was significantly reduced by treatment with glyburide, an inhibitor of
      ATP-binding cassette transporter A1 (ABCA1). These results suggest that apoE
      containing HDL, unlike apoE-deficient HDL, is involved in cholesterol efflux via
      ABCA1.

PMID- 30210054
TI  - Hyperspectral imaging as a possible tool for visualization of changes in
      hemoglobin oxygenation in patients with deficient hemodynamics - proof of
      concept.
AB  - There is a lack of imaging tools for the evaluation of spatial alterations in
      microcirculation including blood oxygen saturation and hemoglobin distribution
      but recent innovative developments in hyperspectral technology may offer a
      solution. We examined different hemodynamic disorders in patients suffering from
      scleroderma, Dupuytren surgery, chronic foot ulcera and skin infections.
      Superficial and deeper blood oxygen saturation, hemoglobin distribution and water
      content were determined using hyperspectral imaging (HSI). In the patient with
      scleroderma, distinct cutaneous low perfused regions correlated with macroscopic
      skin aspects and seem to be potential therapy control marker. With HSI accurate
      clinical evaluation of a macroscopic conspicuous wound after Dupuytren surgery
      was possible and influenced further surveillance decisions. HSI clearly revealed
      the spatial geometry and also the clinically related perfusion parameters of
      abscess formation and chronic ulcer wounds. The hemodynamically relevant
      parameters like blood oxygen saturation (1 mm to approx. 6 mm subcutaneous),
      total hemoglobin distribution and tissue water content can be easily determined
      and visualized with HSI in near real time. Hence, this technique seems to be
      suitable for routine diagnostics of acute and chronic wounds as well as for the
      examination of systemic hemodynamic disturbances. Special indications may be
      transplant surveillance and monitoring of therapeutical interventions.

PMID- 30210055
TI  - Student Preparation for Nursing Leadership: Lessons from an Undergraduate
      Programs Review.
AB  - Facilitating student achievement of nationally recognized entry-level
      competencies in nursing leadership is a critical step in building capacity to
      promote patient safety, quality of care, and healthy work environments. Data for
      this substudy were drawn from a larger multi-phased, multi-method, cross
      sectional, descriptive study conducted to inform comprehensive undergraduate
      curricular revision. The research question for this substudy was: what are the
      perceptions about undergraduate program preparation for nursing leadership?
      Frequencies and percentages summarized relevant quantitative data from the
      surveys and deductive content analysis was used to further explore the category
      of leadership which emerged from content analysis of qualitative data in the
      larger study. Key findings illustrate need for additional attention to learning
      experiences in conflict management, delegation and supervision of clinical teams,
      and advocacy. Greater collaboration between educational and clinical agencies is
      needed to find mutually beneficial strategies to support nursing leadership
      development for nursing students and new graduates.

PMID- 30210056
TI  - Prognostic value of the aortic isthmus Doppler assessment on late onset fetal
      growth restriction.
AB  - Objectives As conflicting results have been reported about the association of
      reversed flow on the aortic isthmus (AoI) and adverse perinatal results in fetal
      growth restriction (FGR), we aim to compare perinatal outcomes (including
      tolerance to labor induction) of late-onset FGR between those with anterograde
      and reversed AoI flow. Methods This was an observational retrospective cohort
      study on 148 singleton gestations diagnosed with late-onset FGR (diagnosis >=32+0
      weeks), with an estimated fetal weight (EFW) <10th centile and mild fetal Doppler
      alteration: umbilical artery (UA) pulsatility index (PI) >95th centile, middle
      cerebral artery (MCA)-PI <5th centile or cerebral-placental ratio <5th centile.
      Anterograde AoI flow was present in n=79 and reversed AoI flow in n=69. Delivery
      was recommended from 37 weeks in both groups. Perinatal results were compared
      between the groups. Results The global percentage of vaginal delivery of fetuses
      with anterograde and reversed blood flow was 55.7% vs. 66.7% (P=0.18) and the
      percentage of cesarean section (C-section) for non-reassuring fetal status was
      12.7% vs. 15.9% (P=0.29), respectively. When evaluating those that underwent
      labor induction, the vaginal delivery rate was 67.9% vs. 77.2% (P=0.17),
      respectively. There were no significant differences regarding any other perinatal
      variables and there were no cases of severe morbidity or mortality. Conclusions
      We observed that the presence of reversed AoI flow does not worsen perinatal
      outcomes on fetuses with late-onset growth restriction with mild Doppler
      alterations. Attempt of labor induction is feasible in these fetuses regardless
      of the direction of AoI flow.

PMID- 30210057
TI  - Sofosbuvir/velpatasvir/voxilaprevir: a highly effective option for retreatment of
      hepatitis C in difficult-to-treat patients.
AB  - Treatment for hepatitis C has escalated rapidly since the advent of direct-acting
      antivirals. Although there are highly efficacious, pangenotypic regimens
      available as standard of care, 5-10% of patients do not achieve virological cure.
      The recently approved fixed-dose combination of sofosbuvir, velpatasvir and
      voxilaprevir provides an option for retreatment in patients who have failed prior
      regimens and have characteristics which make them difficult to treat. This review
      provides a summary of the evidence for use of Vosevi(r), a fixed-dose combination
      pill for treatment of hepatitis C in treatment-experienced patients.

PMID- 30210058
TI  - Spin-orbital entangled liquid state in the copper oxide Ba3CuSb2O9.
AB  - Structure with orbital degeneracy is unstable toward spontaneous distortion. Such
      orbital correlation usually has a much higher energy scale than spins, and
      therefore, magnetic transition takes place at a much lower temperature, almost
      independently from orbital ordering. However, when the energy scales of orbitals
      and spins meet, there is a possibility of spin-orbital entanglement that would
      stabilize novel ground state such as spin-orbital liquid and random singlet
      state. Here we review on such a novel spin-orbital magnetism found in the
      hexagonal perovskite oxide Ba3CuSb2O9, which hosts a self-organized honeycomblike
      short-range order of a strong Jahn-Teller ion Cu2+. Comprehensive structural and
      magnetic measurements have revealed that the system has neither magnetic nor Jahn
      Teller transition down to the lowest temperatures, and Cu spins and orbitals
      retain the hexagonal symmetry and paramagnetic state. Various macroscopic and
      microscopic measurements all indicate that spins and orbitals remain fluctuating
      down to low temperatures without freezing, forming a spin-orbital entangled
      liquid state.

PMID- 30210059
TI  - Peculiar magnetism in Eu substituted BiFeO3 and its correlation with local
      structure.
AB  - We have systematically investigated the effects of Eu substitution on chemical
      pressure, bond lengths, microstrain, bond angles, octahedral tilting, vibrational
      modes and phase transformation, in BiFeO3. Correlation between concentration,
      phase, local structure and magnetism has been explained. Substitution of Eu ions
      with contrasting magnetic moment and dissimilar size, affects the local structure
      by changing bond angles and hence modifies spin structure through weakening of
      Dzyaloshinsky-Moriya (DM) interaction which lead to destruction of spiral spin
      configuration. Intriguing as well as anomalous magnetic response such as weak
      ferromagnetism with high coercivity, stair step like loops with significant drop
      in coercivity and systematic decrease in the magnetic coercivity at low
      temperatures has been observed as a function of Eu concentration (x). These
      results are explained on the basis of weakening of DM interaction, field induced
      melting of antiferromagnetic clusters and modification in effective magnetic
      anisotropy including contribution of magnetoelectric coupling, for various values
      of x. These results were used to generate the magnetic phase diagram.

PMID- 30210060
TI  - Anomalous heat flow in 8-Pmmn borophene with tilted Dirac cones.
AB  - We analytically establish an anomalous transverse flow of heat in 8- Pmmn
      borophene, one of the several two-dimensional allotropes of Boron. The dispersion
      of this allotrope contains a pair of anisotropic and tilted Dirac cones which are
      gapped by placing the 2D B sheet under an intense circularly-polarized
      illumination. A gap in the Dirac dispersion leads to a finite Berry curvature and
      connected anomalous Hall effects. In the case of thermoelectrics, this manifests
      as a heat current perpendicular to the temperature gradient-the thermal Hall
      effect. A quantitative calculation of the attendant thermal Hall conductivity
      reveals dependence on the intrinsic anisotropy and tilt of the Dirac cone.
      Further, by estimating the longitudinal thermal conductivity using the Wiedemann
      Franz law, we also outline steps to compute the thermal Hall angle that gauges
      the generation efficiency of such transverse heat processes. Finally, we touch
      upon the idea of thermal rectification wherein the direction of flow of the
      anomalous heat reverses through a simple switch of the polarization of incident
      light and is of interest in thermal logic circuits.

PMID- 30210061
TI  - 3D Printed lattice microstructures to mimic soft biological materials.
AB  - OBJECTIVE: Our group has developed a method for 3D printing mechanically
      realistic soft tissue, as a building block towards developing anatomically
      realistic 3D-printed biomechanical testbed models. METHODS: A Polyjet 3D printer
      was used to print lattice microstructures, which were tested in compression to
      evaluate the elastic profile. Lattice properties including element diameter,
      element spacing (ES), element cross-sectional geometry, element arrangement, and
      lattice rotation were varied to determine their effect on the stress-strain
      curve. As a case study, a single 3D printed sample was tuned such that its
      elastic profile matched plantar fat. RESULTS: Element diameter and ES had the
      largest effect on the stress-strain profile, and rotating the lattice
      microstructure tends to linearize the curves. A simple cubic lattice
      microstructure of cylindrical elements, with 0.5 mm diameter columns and 1.2 mm
      spacing had a stress-strain curve the was closest to plantar fat. The elastic
      modulus at 10, 30, and 50% strain was 7.55, 9.50, and 252 kPa respectively.
      Physiologic plantar fat at the same strain values has moduli values of 1.08,
      7.13, and 188 kPa. SIGNIFICANCE: We demonstrated that lattice microstructures can
      decrease the young's modulus of soft 3D printed materials by three orders of
      magnitude. By creating a method for fine-tuning the elastic profile of 3D-printed
      materials to behave like human soft tissue, we provide an attractive alternative
      to more exotic and time-consuming techniques such as molding and casting.

PMID- 30210062
TI  - Topological order, emergent gauge fields, and Fermi surface reconstruction.
AB  - This review describes how topological order associated with the presence of
      emergent gauge fields can reconstruct Fermi surfaces of metals, even in the
      absence of translational symmetry breaking. We begin with an introduction to
      topological order using Wegner's quantum [Formula: see text] gauge theory on the
      square lattice: the topological state is characterized by the expulsion of
      defects, carrying [Formula: see text] magnetic flux. The interplay between
      topological order and the breaking of global symmetry is described by the non
      zero temperature statistical mechanics of classical XY models in dimension D  = 
      3; such models also describe the zero temperature quantum phases of bosons with
      short-range interactions on the square lattice at integer filling. The
      topological state is again characterized by the expulsion of certain defects, in
      a state with fluctuating symmetry-breaking order, along with the presence of
      emergent gauge fields. The phase diagrams of the [Formula: see text] gauge theory
      and the XY models are obtained by embedding them in U(1) gauge theories, and by
      studying their Higgs and confining phases. These ideas are then applied to the
      single-band Hubbard model on the square lattice. A SU(2) gauge theory describes
      the fluctuations of spin-density-wave order, and its phase diagram is presented
      by analogy to the XY models. We obtain a class of zero temperature metallic
      states with fluctuating spin-density wave order, topological order associated
      with defect expulsion, deconfined emergent gauge fields, reconstructed Fermi
      surfaces (with 'chargon' or electron-like quasiparticles), but no broken
      symmetry. We conclude with the application of such metallic states to the
      pseudogap phase of the cuprates, and note the recent comparison with numerical
      studies of the Hubbard model and photoemission observations of the electron-doped
      cuprates. In a detour, we also discuss the influence of Berry phases, and how
      they can lead to deconfined quantum critical points: this applies to bosons on
      the square lattice at half-integer filling, and to quantum dimer models.

PMID- 30210063
TI  - Theoretical investigation of multiferroic metal-organic framework magnet
      [CH3NH3][Co(HCOO)3]: Green's function method.
AB  - For the first presented magnetic ordering-induced multiferroics with a metal
      organic framework (MOF) of formula [CH3NH3][Co(HCOO)3], we theoretically
      investigate its multiple ferroics. It is found that Dzyaloshinskii-Moriya
      interaction is a main cause that leads to non-zero magnetization, and electric
      polarization, and the induced electric polarization can be regulated by magnetic
      fields. As an assistant mechanism, magnon-magnon interaction and quantum
      fluctuation play an important role on ferroelectrics and magnetism. Our methods
      are based on the double-time Green's function and Holstein-Primakoff
      transformation. Theoretical results can be compared with experiments, though
      there are some discrepancies.

PMID- 30210064
TI  - Utility of monoclonal PAX8 antibody for distinguishing intrathyroid thymic
      carcinoma from follicular cell-derived thyroid carcinoma.
AB  - Follicular cell-derived thyroid carcinomas, including thyroid squamous cell
      carcinomas (SCCs) and anaplastic carcinomas, are immunoreactive for paired-box
      gene 8 (PAX8), while non-follicular cell-derived thyroid carcinomas stain
      negative for the PAX8 antibody. Intrathyroid thymic carcinoma (ITTC) arising from
      the intrathyroidal ectopic thymus exhibits moderate-to-strong nuclear reactivity
      for polyclonal PAX8. This is difficult to understand given that PAX8 is not
      associated with embryonic thymic development. We aimed to determine the
      diagnostic significance of monoclonal PAX8 antibody in distinguishing ITTCs from
      follicular cell-derived thyroid carcinomas. Ten ITTCs, 14 poorly differentiated
      thyroid carcinomas (PDTCs), 14 thyroid SCCs, 7 thymic tissue specimens, 7
      thymomas, and 1 thymic carcinoma were analyzed using antibodies against
      polyclonal and monoclonal PAX8, thyroid transcription factor-1, p63, and CD5.
      Four ITTCs (40.0%) stained positive for polyclonal PAX8; none stained positive
      for monoclonal PAX8. All PDTCs and 92.9% of SCCs were immunoreactive for both
      polyclonal and monoclonal PAX8. All PDTCs, 46.2% of SCCs, and none of the ITTCs
      were immunoreactive for thyroid transcription factor-1. Eight ITTCs (80.0%), but
      none of the PDTCs and SCCs, were immunoreactive for CD5. We are the first to show
      that ITTCs stain negative for monoclonal PAX8. Monoclonal PAX8 is a more reliable
      marker than polyclonal PAX8 for determining follicular cell origin. We conclude
      that monoclonal PAX8 is a useful marker for distinguishing ITTCs from PDTCs and
      SCCs. Monoclonal PAX8 negativity is additional evidence in support of ITTCs not
      being follicular cell-derived thyroid carcinomas, but having a thymic origin.

PMID- 30210065
TI  - [Applications of Raman Spectroscopy on Quality Control of Hospital Formulations].
AB  - Hospital formulation has several advantages, including the flexibility of
      customization as per the disease state or the patients' precise requirements.
      However, compared with commercial formulations, hospital formulations are usually
      not under the same level of quality check. In the present study, we tested mixed
      powder formulations prepared in a hospital pharmacy using Raman spectroscopy to
      investigate the feasibility of applying Raman spectroscopy as a quality-control
      tool of hospital formulations. For this purpose, we first established a numerical
      evaluation method to determine the uniformity of a powder mixture using Raman
      chemical imaging data with atropine sulfate/lactose mixture samples and revealed
      that the mixing uniformity correlated to the experience level of the pharmacist.
      Next, we developed a content quantification method in a one-dose packaged powder
      formulation by measuring the Raman spectra from the outside of the package.
      Because this method allows for quantification of the components inside the
      package in a non-destructive and non-contact manner, it can be applied for
      content confirmation after one-dose packaging. Using this method, the content
      uniformity of the mixed powder formulation in the one-dose package was compared
      between the formulations prepared by the pharmacists and those prepared by a
      pharmacy robot. Our study indicates the possibility of applying Raman
      spectroscopy as a quality-control tool of hospital formulations. Studies on
      further applications of Raman spectroscopy in the field of clinical pharmacology
      are expected.

PMID- 30210066
TI  - Protective antibody response of Balb/c mice to Bali rabies virus isolate
      propagated in BHK-21 cells.
AB  - The protective antibody response of Balb/c mice to Bali rabies virus (RABV) in
      BHK-21 cells was studied. The virus was isolated from a rabid dog and was adapted
      to replicate in BHK-21 cell culture for seven passages. The BHK-21-adapted Bali
      RABV (BHK-Bali RABV) was inactivated with binary ethylenimine and 24 mice were
      immunized twice at 21-days intervals with the inactivated virus and Rabisin(r)
      vaccine. Virus replication was detected using indirect immunofluorescence,
      immunocytochemistry, and western blotting assays. Enzyme-linked immunosorbent
      assay examination 2 weeks after the first immunization revealed RABV antibody
      titers that were mostly below the minimum protective level (<0.5 equivalent unit,
      EU). Antibody titers increased sharply after the second immunization. Antibody
      titers in serum of mice induced by inactivated BHK-Bali RABV one week after the
      second immunization were slightly lower (0.8-3.8 EU) than those induced by
      Rabisin vaccine (0.9-6.3 EU). RABV antibody titers were stable for at least 6
      weeks after the second immunization. Both Rabisin vaccine and inactivated BHK
      Bali RABV induced neutralizing antibodies with neutralization titers (50%
      protective dose per ml) of 29.84 for 0.1 ml Rabisin, 211.41 for 0.2 ml Rabisin,
      27.41 for 0.1 ml BHK-Bali RABV, and 28.25 for 0.2 ml BHK-Bali RABV. Thus,
      inactivated BHK-Bali RABV induces a protective immune response in Balb/c mice,
      but at lower levels compared to induction by Rabisin vaccine.

PMID- 30210067
TI  - Influence of swine leukocyte antigen haplotype on serum antibody titers against
      swine erysipelas vaccine and reproductive and meat production traits of SLA
      defined selectively bred Duroc pigs.
AB  - We investigated possible associations of SLA class II haplotypes with serum
      antibody titers against a swine erysipelas vaccine, reproductive and meat
      production traits using a population of selective breeding Duroc pigs. In the
      selective breeding Duroc pigs, four SLA class II-DRB1 and -DQB1 alleles were
      assigned by using PCR-sequence specific primer technique. Low-resolution
      haplotype (Lr)-0.30 and/or Lr-0.13 were deduced from the SLA class II alleles in
      the population of SLA-defined Duroc pigs. SLA-homozygous piglets with the Lr-0.30
      haplotype had relatively lower serum antibody titers against the vaccine compared
      to those with Lr-0.13. In contrast, there were no statistically significant
      differences in reproductive performance between the SLA-defined pigs with two SLA
      class II haplotypes. Weaning and rearing rates until the body weight of 105 kg
      was reached in homozygous piglets with Lr-0.30 were significantly lower than
      those in homozygous piglets with Lr-0.13. The SLA-defined pigs had lower birth
      and weaning weights, body weights at 60 days of age, and daily weight gains than
      non-selective breeding Duroc pigs. Furthermore, the SLA-defined pigs had slightly
      lower back fat thickness compared to the non-selective breeding pigs. The rib eye
      areas of homozygous or heterozygous pigs with Lr-0.13 were larger than those of
      homozygous pigs with Lr-0.30 and non-selective breeding pigs. These data
      suggested that SLA haplotypes had the potential as useful genetic markers for
      selective breeding in the population of SLA-defined Duroc pigs.

PMID- 30210068
TI  - Independent chondrogenic potential of canine bone marrow-derived mesenchymal stem
      cells in monolayer expansion cultures decreases in a passage-dependent pattern.
AB  - Although chondroinductive growth factors are considered necessary for
      chondrogenesis of bone marrow-derived mesenchymal stem cells (BMSC), independent
      and spontaneous chondrogenesis has been previously demonstrated in adult horses,
      bovine calves and adult human BMSC. Surprisingly, adult canine BMSC under similar
      culture conditions previously failed to demonstrate chondrogenesis. The present
      study evaluated independent chondrogenic potential of BMSC sourced from three
      young dogs in the absence of known chondroinductive factors. BMSC were culture
      expanded in 10% DMEM up to third passage (P3). At each passage, the phenotype of
      BMSC was evaluated by RT-PCR gel electrophoresis and qPCR. BMSC exhibited a
      chondrogenic phenotype in the absence of dexamethasone and TGF-beta1 as verified
      by the expression of Sox-9, type II collagen and aggrecan. Sox-9 was
      significantly downregulated (P<0.05) from P1-P3 compared to P0 while type II and
      X collagen, and aggrecan were significantly downregulated at P3 compared to P0.
      There was a significant (P<0.01) negative correlation between passaging and Sox
      9, type II collagen and aggrecan gene expression. These results indicate that
      independent chondrogenic potential and phenotype retention of BMSC decreases in a
      passage-dependent pattern. Therefore, caution should be exercised for future
      experiments evaluating the chondrogenic potential of BMSC after extensive
      expansion cultures in 10% DMEM.

PMID- 30210069
TI  - System for the heterologous expression of NS1 protein of H9N2 avian influenza
      virus in the ciliate Tetrahymena thermophila.
AB  - Tetrahymena is commonly used as an alternative eukaryotic system for efficiently
      expressing heterologous genes. In this study, we inserted the non-structural (NS)
      1 gene of avian influenza virus (AIV) into the shuttle vector pD5H8 and
      transformed conjugating T. thermophila with the recombinant plasmid pD5H8-NS1 by
      particle bombardment. Positive transformants were selected with paromomycin. We
      demonstrated that the NS1 protein could be expressed steadily following induction
      with cadmium in this Tetrahymena system. An enzyme-linked immunosorbent assay
      detection method was preliminary established using the expressed protein as
      coating antigens for serodiagnosis. This is the first study in which a
      Tetrahymena expression system was employed for the expression of the AIV NS1
      protein, and it provides a good basis for the development of differential
      diagnostic kits and vaccines for the prevention and control of avian influenza.

PMID- 30210070
TI  - Transcatheter Repair of Functional Mitral Regurgitation in Heart Failure Patients
      - A Meta-Analysis of 23 Studies on MitraClip Implantation.
AB  - BACKGROUND: The aim of this study was to investigate long-term survival, clinical
      status, and echocardiographic findings of patients with severe functional mitral
      regurgitation (FMR) undergoing MitraClip (MC) treatment and to explore the role
      of baseline features on outcome. Methods and Results: Randomized and
      observational studies of FMR patients undergoing MC treatment were collected to
      evaluate the overall survival, New York Heart Association (NYHA) class and
      echocardiographic changes after MC treatment. Baseline parameters associated with
      mortality and echocardiographic changes were also investigated. Across 23 studies
      enrolling 3,253 patients, the inhospital death rate was 2.31%, whereas the
      mortality rate was 5.37% at 1 month, 11.87% at 6 months, 18.47% at 1 year and
      31.08% at 2 years. Mitral regurgitation Grade <3+ was observed in 92.76% patients
      at discharge and in 83.36% patients at follow-up. At follow-up, 76.63% of
      patients NYHA Class I-II and there were significant improvements in left
      ventricular (LV) volume, ejection fraction, and pulmonary pressure. Atrial
      fibrillation (AF) had a significant negative effect on 1-year survival
      (beta=0.18+/-0.06; P=0.0047) and on the reduction in LV end-diastolic and end
      systolic volumes (beta=-1.05+/-0.47 [P=0.0248] and beta=-2.60+/-0.53 [P=0.0024],
      respectively). CONCLUSIONS: MC results in durable reductions in mitral
      regurgitation associated with significant clinical and echocardiographic
      improvements in heart failure patients. AF negatively affects LV reverse
      remodeling and 1-year survival after MC treatment.

PMID- 30210071
TI  - PARALLEL-HF - A Paradigm Shift for Heart Failure Treatment in Japan?

PMID- 30210072
TI  - Stability of selected enzymes in saliva of pigs under different storage
      conditions: a pilot study.
AB  - Stability of alpha-amylase (alpha-A), butyrylcholinesterase (BChE), lipase,
      adenosine deaminase (ADA) and total esterase activity (TEA) in two pools of
      porcine saliva was studied after 1 and 4 days at 4 degrees C, and after 30, 90
      and 360 days at -20 degrees  and -80 degrees C. At 4 degrees C, BChE, lipase and
      TEA were stable less than 1 day, alpha-A less than 4 days and ADA for up to 4
      days. At -20 degrees C, BChE and TEA were stable less than 30 days, alpha-A and
      lipase less than 90 days and ADA up to 360 days. At -80 degrees C, TEA was stable
      less than 30 days, alpha-A and lipase less than 360 days, and BChE and ADA for up
      to 360 days.

PMID- 30210073
TI  - Characteristic Aroma Components from Dried "Wakame" Undaria pinnatifida.
AB  - An essential oil from dried "wakame" (Undaria pinnatifida), prepared by a
      simultaneous distillation extraction method, was analyzed by GC-MS, indicating
      the presence of one major component of volatiles. The volatile component was
      identified as (6Z,9Z,12Z,15Z,18Z)-1,6,9,12,15,18-henicosahexaene by comparison
      with the GC-MS and NMR spectra of synthetic. The henicosahexaene showed a subtly
      marine aroma. (6Z,9Z,12Z,15Z)-1,6,9,12,15-Henicosapentaene was also detected as a
      minor polyene in the essential oils. It was suggested that these polyenes
      contribute to the characteristic aroma of the dried wakame.

PMID- 30210074
TI  - Lipase - catalyzed Modification of Rice Bran Oil Solid Fat Fraction.
AB  - This study used a rice bran oil solid fat fraction (RBOSF) to produce cocoa
      butter alternatives via interesterification reaction catalyzed by immobilized
      lipase (Lipozyme(r) RM IM) in hexane. Effects of reaction time (6, 12, and 18 h),
      temperature (55, 60, and 65 degrees C), mole ratios of 3 substrates [RBOSF:palm
      olein:C18:0 donors (1:1:2, 1:2:3, and 1:2:6)] were determined. The substrate
      system was dissolved in 3 mL of hexane and 10% of lipase was added. Two sources
      of C18:0 donors, stearic acid (SAd) and ethyl stearate (ESd) were used.
      Pancreatic lipase - catalyzed sn-2 positional analysis was also performed on both
      substrates and structured lipids (interesterification products). Structured
      lipids (SL) were analyzed by gas - liquid chromatography (G40.35LC) for fatty
      acid composition. Major fatty acids of RBOSF were C18:1, oleic acid (OA, 41.15+/
      0.01%), C18:2, linoleic acid (LA, 30.05+/-0.01%) and C16:0, palmitic acid (PA,
      22.64+/-0.01%), respectively. A commercial raw cocoa butter (CB) contained C18:0,
      stearic acid (SA, 33.13+/-0.04%), OA (32.52+/-0.03%), and PA (28.90+/-0.01%),
      respectively. Fatty acids at sn-2 position of RBOSF were OA (46.52+/-0.63%) and
      LA (42.98+/-1.1%), while major fatty acid at sn-2 position of CB was OA (85.24+/
      1.22%). The RBOSF had low SA (2.40+/-0.01%) compared to CB (33.13+/-0.04%). The
      content of OA (46.52+/-0.63%) at sn-2 position in RBOSF was half of that found in
      CB (85.24+/-1.22%). Optimal reaction was 1:2:6 mole ratio of the substrate
      (RBOSF:PO:SAd), at 65 degrees C for 12 h. Fatty acid compositions of the SL were
      31.72+/-0.99% SA, 30.91+/-0.53% LA, 23.18+/-0.32% OA, and 13.26+/-0.34% PA,
      respectively. Fatty acids at sn-2 position of the SL were 53.72+/-4.21% OA,
      25.11+/-3.69% LA, 14.18+/-1.58% PA, and 6.99+/-0.02% SA, respectively. DSC curves
      showed the melting point of CB at 20.94 degrees C, while those of the SL were
      14.15 and 40.35 degrees C, respectively. The melting completion temperature (Tmc)
      of CB was 25.5 degrees C while that of SL was 43.9 degrees C, respectively.

PMID- 30210075
TI  - N,N-Disubstituted Allylic Amine Type Aminophosphines with C(aryl)-N(amine) Bond
      Axial Chirality: Synthesis and Application to Palladium-Catalyzed Asymmetric
      Allylic Alkylation with Malonates.
AB  - We designed and synthesized a series of N,N-disubstituted allylic amine type
      aminophosphines 2, 3 and 4, which are derivatives of chiral ligands 1.
      Aminophosphines 2-4 (except 2a) exist in C(aryl)-N(amine) bond axial chirality by
      chiral HPLC analysis. Both enantiomeric isomers of 4b were successfully obtained
      in an enantiomerically pure form. We demonstrated that 1a, 1b, and 4b can be used
      as effective chiral ligands for the palladium-catalyzed asymmetric allylic
      alkylation of 1,3-diphenyl-2-propenyl acetate with malonates in high
      enantioselectivities (up to 90% ee).

PMID- 30210077
TI  - Quantitative 31P NMR Method for Individual and Concomitant Determination of
      Phospholipid Classes in Polar Lipid Samples.
AB  - Herein, to achieve individual and concomitant quantifications of phospholipid
      classes, an absolute quantification 31P NMR method using an internal standard was
      examined. Phospholipid standards and dietary foods were dispersed to prepare test
      solutions in an anionic surfactant (sodium cholate) solution containing EDTA, as
      a modification based on a reported method. Each phospholipid class showed a
      reproducible chemical shift at a near-neutral test solution pH of 6.90+/-0.04 and
      temperature of 30.0+/-0.1 degrees C. The quantity of synthetic
      phosphatidylcholine measured using 31P NMR was consistent with that measured by
      1H NMR using an internal standard. As the principal phospholipid class of soybean
      and egg yolk lecithin is phosphatidylcholine, the measurement conditions of 31P
      NMR (pulse interval time and number of scans) were optimized such that minor
      phospholipids, including lysophospholipids, also present in lecithin could be
      quantified simultaneously. Phospholipid classes in commercial polar lipid samples
      derived from porcine brain, yeast, and soybean were individually quantified using
      the above conditions. Using phosphoserine as the internal standard material
      allowed the absolute molar quantity of the phospholipid class to be precisely
      determined with traceability to the SI. The determined molar amounts of
      phospholipid classes were then translated to the weight amount by assuming that
      each phospholipid class contained two stearic acid molecules as the constituent
      fatty acid. The calculated total contents of each phospholipid class by 31P NMR
      were in good agreement with those obtained by molybdenum blue colorimetry.
      Furthermore, the quantitative values of the principal phospholipid classes in the
      polar lipid samples obtained by 31P NMR corresponded in a broad view, however,
      was more informative for the separation of individual phospholipid species rather
      than the quantitative 2D thin-layer chromatography.

PMID- 30210076
TI  - Optimization of Microwave-assisted Extraction of Essential Oil from Lavender
      Using Response Surface Methodology.
AB  - A microwave-assisted hydrodistillation (MAHD) method was investigated for
      extraction of essential oils from lavender. The essential oil extracts at
      optimized MAHD conditions was compared with hydrodistillation (HD). Response
      surface methodology coupled with Box-Behnken design was applied to optimize the
      parameters for MAHD. The optimized MAHD conditions were 500 W microwave power, 17
      mL/g liquid-to-solid ratio and 40 min microwave time. The ANOVA results revealed
      that microwave time had the greatest impact on the essential oil yield followed
      by liquid-to-solid ratio and microwave power. Under the MAHD optimized
      conditions, the essential oil yield was 3.19%, approximating the predicted yield
      (3.20%). MAHD was superior in terms of saving energy and extraction time (40 min,
      compared to 120 min in HD). The essential oil analyzed by GC-MS, presented 39
      compounds constituting 98.37% and 97.51% of the essential oils obtained through
      MAHD and HD, respectively. No obvious differences were found in composition
      between MAHD oil and HD oil. Antimicrobial study showed that the lavender
      essential oil exhibited broad-spectrum antibacterial activity and the MAHD oil
      showed a higher antimicrobial activity than the HD oil. This study revealed that
      MAHD could be a good method for extracting essential oil in lavender and other
      aromatic plants.

PMID- 30210078
TI  - Effect of Hazelnut Oil on Muscle Cell Signalling and Differentiation.
AB  - Nuts-enriched diets were shown to bear beneficial effects for human's health.
      Among nuts, hazelnut plays a major role in human nutrition and health because of
      its unique fatty acid composition (predominantly MUFA), fat soluble bioactives
      (tocopherols and phytosterols), vitamins (vitamin E), essential minerals
      (selenium), essential amino acids, antioxidant phenolics (caffeic acid), dietary
      fiber (soluble form), and bioactive phtytochemicals. The current study was
      designed to explore the cellular effects of two particular hazelnut strains (Ordu
      and Tonda).Four hazelnut oils were obtained from 2 common strains (Ordu hazelnut
      oil, Ordu cuticle oil, Tonda "gentile" hazelnut oil, Tonda "gentile" cuticle
      oil). The metabolic and nutritional effects of the four hazelnut oils were
      assessed using an in vitro model of mouse myoblasts, identifying the
      intracellular mechanisms involved in muscle differentiation and in the modulation
      of specific muscle genes.We demonstrated that hazelnut oils induced morphological
      changes in neo-formed myotubes increasing myotubes size. In particular, the
      diversified effects of the hazelnuts and cuticle oils on muscle fibres shape (on
      length and diameter respectively) determine a diversified pattern of action on
      elongation or hypertrophy of the muscle fibres. Furthermore, hazelnut oils
      regulate different pathways associated with myoblasts growth and development,
      stimulate signal transduction, and activate cell commitment and differentiation.
      The present results provide evidence that hazelnut oils may affect skeletal
      muscle growth and differentiation, constituting the proof of principle for the
      future development of novel foods and integrators.

PMID- 30210079
TI  - Biotransformation of (+)-Carvone and (-)-Carvone by the Common Cutworm Spodoptera
      litura Larvae.
AB  - Biotransformation of (+)- and (-)-carvone (1 and 2) by the larvae of common
      cutworm (Spodoptera litura) has been investigated. (+)-Carvone was transformed to
      (+)-(4S)-10-hydroxycarvone (1-1), (+)-(4S)-7- hydroxycarvone (1-2), and (-)-(4S)
      8,9-dihydroxy-8,9-dihydrocarvone (1-3). (-)-Carvone (2) was transformed to (-)
      (4R)-10-hydroxycarvone (2-1), (-)-(4R)-7-hydroxycarvone (2-2), (+)-(4R)-8,9
      dihydroxy-8,9- dihydrocarvone (2-3), and (-)-(2R,4R)-10-hydroxycarveol (2-4). The
      results indicate that the main metabolic reaction of carvones by S. litura larvae
      is oxidation at vinyl group (C-8 and C-9).

PMID- 30210080
TI  - Physicochemical, Rheological and Sensory Properties of Different Brands of Sesame
      Pastes.
AB  - The chemical characteristics, rheological properties and sensory evaluation of
      nine different brands of the sesame pastes were investigated. The sesame pastes
      showed a significant difference for the crude fat, protein, crude fibre, total
      sugars, total ash, moisture content, and acid values (p < 0.05). The fat content
      ranged from 51.80% to 61.56%, and the protein content varied between 16.08% and
      18.97%. All sesame paste samples are pseudoplastic materials. The flow indexes
      lied between 0.67 and 0.81 for the tested sesame pastes (p > 0.05). The
      consistency coefficient of the different sesame paste brands varied significantly
      (p < 0.05), ranging from 4.48 to 24.21 Pa?sn, indicating that the consistency
      coefficient is a more sensitive parameter for measuring the flow behaviour of
      foodstuff. The areas of the hysteresis loops of the white-sesame paste of
      "Haoweisi" brand and the black-sesame paste of "A Yimeng couple" brand were
      higher than the other sesame pastes, indicating that these two samples were
      difficult to be restored to their original structures and such restoration
      required a longer time. Both Storage modulus (G') and loss modulus (G") of the
      sesame pastes increased with increasing frequency, and G' values were greater
      than the G" values, exhibiting the typical properties of the viscoelastic solid,
      the results may provide the valuable reference for choosing the sesame pastes as
      the spreadable butters or salad dressings, and for further processing.

PMID- 30210083
TI  - MitraClip in Patients With Severe Mitral Regurgitation and Severe Left
      Ventricular Systolic Dysfunction.

PMID- 30210081
TI  - Proprotein Convertase Subtilisin/Kexin Type 9 Is Associated with Degenerating
      Adipocytes in Abdominal Aortic Aneurysm.
AB  - Abdominal aortic aneurysm (AAA) is a common disease among the elderly. Recently,
      proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been
      indicated as useful therapeutic tools for the treatment of cardiovascular
      diseases. The aim of this study was to elucidate the role of PCSK9 in the
      pathogenesis of AAA. We used fluorescence immunohistochemistry to assess the
      expression of PCSK9 in aortic tissues resected from 24 patients with AAA.
      Histological examination showed that PCSK9 expression in the adventitia region of
      the aneurysms was decreased in AAA samples. In the same region, the expression of
      CD36 increased. We hypothesized that CD36 expression might upregulate the
      transport of fatty acids into cells such as the adipocytes, and subsequently
      cause degradation of the adventitia in the aortic wall, contributing to AAA
      development.

PMID- 30210084
TI  - Message From the Editor-in-Chief.

PMID- 30210082
TI  - Anti-Xa Activity and Event Risk in Patients With Direct Factor Xa Inhibitors
      Initiated Early After Stroke.
AB  - BACKGROUND: Measuring anti-Xa activity (AXA) has been reported as useful for
      predicting future risk of hemorrhagic and ischemic events in stroke patients
      taking direct factor Xa inhibitors. We evaluated AXA levels of rivaroxaban or
      apixaban in acute stroke patients with non-valvular atrial fibrillation. Methods
      and Results: This was a single-center, prospective, observational study.
      Consecutive patients with acute ischemic stroke or transient ischemic attack who
      were admitted within 7 days of onset and started taking rivaroxaban or apixaban
      for NVAF between January 2012 and April 2017 were enrolled. AXA was measured at 2
      time points: just before (AXAtrough) and 4 h after (AXApeak) taking rivaroxaban
      or apixaban on the 2nd day or later of administration. Of 156 patients taking
      rivaroxaban, hemorrhagic events occurred in 13. Patients with hemorrhagic events
      had higher AXApeak than those without [median (interquartile range): 1.93 (1.11
      3.75) vs. 1.35 (0.80-2.00) IU/mL; P<0.01]. Multivariable-adjusted Cox models
      showed that AXApeak was independently related to the incidence of hemorrhagic
      events. Of 169 patients taking apixaban, hemorrhagic events occurred in 11.
      Patients with hemorrhagic events had higher AXAtrough [2.78 (1.90-3.53) vs. 1.42
      (0.93-2.08) IU/mL, P<0.01] and AXApeak [4.05 (3.44-4.72) vs. 2.43 (1.79-3.35)
      IU/mL, P<0.01] than those without. Both AXAtrough and AXApeak were independently
      related to the incidence of hemorrhagic events. CONCLUSIONS: In these patients
      who started rivaroxaban or apixaban early after stroke, AXA levels in the early
      period were related to future hemorrhagic events.

PMID- 30210085
TI  - Inequality and Mother's Age as Determinants of Breastfeeding Continuation in
      Bangladesh.
AB  - The World Health Organization recommends continuing breastfeeding up to 2 years
      of age or beyond for sound growth and development of children. In Bangladesh,
      continuation rates for breastfeeding have recently decreased and effective
      measures are required to counter this downward trend. Although recent years have
      seen economic development and reductions in poverty, Bangladesh still has the
      highest rate of child marriage worldwide. Thus, we aimed to clarify the factors
      influencing breastfeeding continuation, especially from the perspective of
      inequality and mother's age in Bangladesh, using data from the Bangladesh
      Demographic and Health Survey 2011. Event history analyses were performed during
      a 24-month follow-up period on 7,041 mothers with duration of breastfeeding as
      the outcome variable, with wealth index (an indicator for inequality) and
      mother's age used as the main explanatory variables. The results showed that
      poorer mothers were on the whole more likely to continue breastfeeding through 24
      months after childbirth, and younger mothers were less likely to continue
      breastfeeding particularly past the first year. However, both younger and older
      mothers continued breastfeeding to the same extent within the first year after
      childbirth. Mother's age had time-varying effects on breastfeeding continuation,
      meaning that the effects on breastfeeding continuation were affected by the
      child's age. These findings imply that policymakers should be aware that efforts
      to reduce child marriage may increase the rate of breastfeeding continuation
      beyond the first year after childbirth. In contrast, efforts at poverty
      alleviation, aimed at preventing child marriage, may decrease the rate
      irrespective of the child's age.

PMID- 30210086
TI  - The Japan Environment and Children's Study (JECS) in Fukushima Prefecture:
      Pregnancy Outcome after the Great East Japan Earthquake.
AB  - Japan Environment and Children's Study (JECS) is nationwide birth cohort study
      that was initiated in January 2011 to investigate the effect of environmental
      factors on children's health. Soon after the JECS started, the Great East Japan
      Earthquake occurred on March 11, 2011, with subsequent nuclear accident at the
      Fukushima Daiichi Nuclear Power Plant, causing catastrophic damage in Fukushima
      Prefecture. After the disaster, JECS was relaunched to cover all areas in
      Fukushima Prefecture due to public concern. In this study, we used the results of
      individuals enrolled in JECS, who gave birth during 2011-2014 in Fukushima
      Prefecture, to elucidate pregnancy outcomes in Fukushima Prefecture. The study
      consisted of 12,804 maternal outcomes. We thus found that the prevalence rates of
      preterm birth < 37 weeks, low birth weight (LBW) < 2,500 g, and LBW < 1,500 g
      were 5.6 %, 9.5%, and 0.8%, respectively; these rates are in accordance with the
      National Vital Statistics of 2014. The proportion of major anomaly among the
      newborns was 1.7%, the value of which was lower than other epidemiological
      studies. This study also found that severe obstetrics outcomes, such as
      hypertensive disorder of pregnancy and placental abruption, were most frequently
      seen among teenage mothers with low socioeconomic status. A prefecture-wide birth
      cohort study following a large-scale disaster may provide valuable information
      for obstetric care providers and residents to improve obstetric and perinatal
      care for pregnant women after a disaster.

PMID- 30210087
TI  - Relation of Elevated Serum Uric Acid Level to Endothelial Dysfunction in Patients
      with Acute Coronary Syndrome.
AB  - AIM: Serum uric acid (SUA) level is known to have a prognostic value in patients
      with acute coronary syndrome (ACS). Endothelial function plays an important role
      in the development of cardiovascular disease. Although relation between SUA level
      and endothelial function has been previously studied in various populations, it
      is partially understood in patients with ACS. METHODS: A total of 55 patients
      with ACS with measurements of SUA level and reactive hyperemia index (RHI) to
      evaluate endothelial function were included. They were classified into three
      groups according to the tertiles of SUA level. The tertiles of SUA level were as
      follows: low tertile, <= 5.2 mg/dl; intermediate tertile, 5.3 to 6.5 mg/dl; and
      high tertile, >= 6.6 mg/dl. RESULTS: Mean SUA level and RHI were 5.8+/-1.5 mg/dl
      and 1.88+/-0.58. There was a significant negative correlation between SUA level
      and RHI (r=-0.41, p=0.002). RHI was stepwisely observed in favor of the higher
      tertile groups (2.14+/-0.74 vs. 1.84+/-0.45 vs. 1.67+/-0.38, p=0.04).
      Multivariate analysis showed elevated SUA level as an independent predictor of
      reduced RHI. CONCLUSION: Elevated SUA level was significantly associated with
      endothelial dysfunction in patients with ACS, possibly leading to subsequent poor
      outcomes following ACS.

PMID- 30210088
TI  - Problems that Physicians should Notice for Better Treatment of
      Hypercholesterolemia in Japan.

PMID- 30210090
TI  - MECHANOMEDICINE: applications of mechanobiology to medical sciences and next
      generation medical technologies.
AB  - Mechanical stress underlies most aspects of cell and organismal biology.
      Mechanomedicine is a field of biology that seeks to understand molecular,
      cellular, tissue, organ, and individual responses to mechanical stimuli and aims
      to apply the gained knowledge to improve health. Combining biology and
      engineering, we explore research areas including mechanosensitive ion channels,
      heart failure, and regenerative medicine.This review will describe our findings
      in mechanobiology, our establishment of a joint venture business as we developed
      devices responding to medical needs, and our alliance with other companies.

PMID- 30210089
TI  - Role of calcium channels and endothelial factors in nickel induced aortic
      hypercontraction in Wistar rats.
AB  - AIM: To investigate the mechanism of nickel augmented phenylephrine (PE)-induced
      contraction in isolated segments of Wistar rat aorta. MATERIALS AND METHODS:
      Effect of varying concentrations of nickel on PE-induced contraction were
      investigated in isolated segments of Wistar rat aorta using an organ bath system.
      Aortic rings were pre-incubated with verapamil (1 uM and 20 uM), gadolinium,
      apocynin, indomethacin or N-G-nitro-L-arginine methyl ester (L-NAME) separately
      before incubation with nickel. RESULTS: Endothelium intact aortic rings incubated
      with 100 nM, 1 uM or 100 uM of nickel exhibited 80%, 43% and 28% increase in PE
      induced contraction, respectively, while no such enhancing responses were
      observed in endothelium denuded aorta. Incubation of aortic rings with 1 uM and
      20 uM verapamil suggested an involvement of influx of calcium through T-type
      calcium channels in smooth muscle cells, while aortic rings pre-incubated with
      gadolinium showed no role of store operated calcium channels in the nickel effect
      on PE-induced contractions. The enhancing effect of nickel on PE-induced
      contractions was inhibited by apocynin, indomethacin or L-NAME. CONCLUSION:
      Nickel has caused augmentation of PE-induced contractions as a result of the
      endothelial generation of reactive oxygen species (ROS) and cyclooxygenase 2
      (COX2) dependent endothelium contracting factors (EDCFs), which increases the
      influx of extracellular calcium through T-type Ca2+ channels in smooth muscle
      cells.

PMID- 30210091
TI  - The effect of avertin anesthesia and a mixture of three types of anesthetic
      agents on food intake and body weight in high fat-induced obese male and female
      mice.
AB  - Basic research on obesity is becoming more important due to an increasing number
      of obese people. Experiments using obesity-model animals often require surgical
      interventions, such as gastric operation, and proper selection of anesthesia is
      important. Avertin, an agent mainly composed of 2,2,2-Tribromoethanol, has been
      used as general anesthesia for a long time, without the use of narcotic drugs. In
      the current study, we found that a single injection of avertin can decrease body
      weight (BW) in male and female C57BL/6J and ICR mice with high fat-diet (HFD)
      induced obesity, but not in standard diet-fed nonobese males and females. Because
      the BW-reducing effect was more prominent in the female mice, we compared the
      effects of avertin and a mixture of three types of anesthetic agents (3MIX),
      which was developed in 2011, on BW reduction in HFD-induced obese female mice.
      Although both avertin and 3MIX decreased food intake and BW, the effects of
      avertin were significantly more potent than those of 3MIX. C-Fos expression, a
      neural activation marker, was dramatically increased in the brain regions related
      to the regulation of both food intake and the autonomic nervous system after
      avertin injection, but not after 3MIX injection. This suggests that avertin
      strongly stimulates the center of feeding regulation and the autonomic nervous
      system and therefore decreases BW. The current study suggests the advantages of
      using 3MIX for surgical interventions in mice in obesity research, as it is ideal
      to prevent anesthesia-induced BW decline.

PMID- 30210092
TI  - Seroprevalence of bovine arboviruses belonging to genus Orthobunyavirus in South
      Korea.
AB  - Arboviruses, belonging to the Simbu serogroup of the genus Orthobunyavirus, often
      cause congenital malformations and reproductive loss in cattle. The recent
      occurrences of such reproductive problems suggest that new arboviruses have
      emerged in Japan. However, there is no information on the presence of these
      viruses in South Korea. The aim of this study was to determine the presence of
      antibodies for Akabane, Aino, Peaton, Sathuperi, and Shamonda viruses in four
      regions, namely Gyeonggi, Jeollabuk, Jeollanam provinces, and Jeju Island of
      South Korea by a serum neutralization test. Antibody positivity against Akabane,
      Aino, Peaton, Sathuperi, and Shamonda viruses was detected in the country, with
      average seropositive rates of 10.4, 4.5, 1.1, 4.9, and 5.6%, respectively.

PMID- 30210093
TI  - Hydropericardium syndrome caused by fowl adenovirus serotype 4 in replacement
      pullets.
AB  - Hydropericardium syndrome (HPS) is one of the important emerging diseases causing
      huge losses to the poultry industry. It affects mainly 3- to 6-week-old broiler
      chickens and rarely occurs in breeding and laying flocks. Recently, an HPS case
      was recorded with a sudden heavy mortality in a 100-day-old laying flock. A fowl
      adenovirus serotype 4 (FAdV-4), named as GDMZ strain, was isolated and identified
      using polymerase chain reaction coupled with electron microscopy. The animal
      experiment showed that a mortality of 100% was recorded with hydropericardium as
      a conspicuous lesion throughout the course of infection. Microscopically,
      vacuolar changes and intranuclear inclusion bodies were observed in the liver and
      vacuolar changes were observed in the heart. The complete genome sequence of GDMZ
      strain was determined to investigate the molecular properties of GDMZ strain. The
      comparative analysis revealed that the novel Chinese FAdV-4 isolate contained
      open reading frame (ORF) 19, ORF27, and ORF48 genomic deletions. The phylogenetic
      analysis revealed that FAdV-4 could be divided into two major clades, of which
      Chinese FAdV-4 were located at a distinct clade.

PMID- 30210094
TI  - Full genome analysis of bovine papillomavirus type 1 derived from a calf with
      severe cutaneous multiple papillomatosis.
AB  - Severe papillomatosis occasionally causes astasia leading to euthanizing cattle.
      There are currently a limited number of reports on virologic approach in severe
      bovine papillomatosis. Here we report a full genome characterization of bovine
      papillomavirus type 1 (BPV-1) from the case of severe papillomatosis. A calf
      developed numerous papillomas on the skin and some nodules in the upper
      gastrointestinal tract at seven months old. The skin lesion was diagnosed as the
      epithelial papilloma with BPV antigen expression, while the gastrointestinal
      lesions were diagnosed as the fibropapilloma without BPV antigen. Full genome
      analysis revealed that BPV-1s detected in all the lesions were exactly the same.
      Compared with the reference BPV-1 sequence, there was a single nucleotide
      insertion in the upstream regulatory region.

PMID- 30210095
TI  - Bovine vegetative endocarditis caused by Streptococcus suis.
AB  - A 5-month-old crossbred beef steer died after exhibiting astasia. A postmortem
      examination revealed verrucous endocarditis and numerous renal hemorrhages. Gram
      positive bacteria were identified in the necrotic lesions of the verruca and
      mitral valve via histopathological analysis. Multifocal necrosis and hemorrhage
      were detected in the renal cortex. Gram-positive cocci isolated from the verruca
      were identified via biochemical tests and 16S rRNA gene sequence analysis as
      Streptococcus suis. Serotyping indicated that the S. suis isolates were
      untypable, following which these isolates were classified as a new sequence type
      (ST1000) via multi-locus sequence typing. S. suis is an important pathogen of
      pigs. However, clinical cases in cattle are rare. This report is intended to
      provide information that may be useful in the diagnosis of streptococcal disease
      in cattle.

PMID- 30210096
TI  - The impact of work rest scheduling for prolonged standing activity.
AB  - Prolonged standing can cause discomfort on the body of the workers and can lead
      to injury and occupational disease. One of the ergonomic intervention is through
      improving the work-rest scheduling. The purpose of this study are to identify the
      fatigue level from the perception of the worker and to investigate the impact of
      the work-rest scheduling to the standing workers for 12 h working time with a
      different gender. This study involved two methods which are self-assessment of
      the worker and direct measurement by using electromyography (EMG). For self
      assessment, 80 workers have been interviewed using questionnaire in order to
      identify the fatigue level. For direct measurement, EMG was attached to the 15
      selected workers at their respective leg and lower back to analyse the muscle
      efforts. In terms of perception, the results show the discomfort and fatigue
      level at the lower body region in the following order as foot ankle, lower back
      and leg. There is a significant difference between gender on discomfort pain for
      foot ankle and leg. The results show short frequent break by 10 min can reduce
      the fatigue at the leg and infrequent long break is preferable in order to reduce
      the fatigue at the lower back. In conclusion, it was found that prolonged
      standing affect the muscle fatigue and discomfort especially lower extremities
      such as foot ankle, lower back and leg. Besides that, different type of work rest
      scheduling and gender have significant result towards the muscle fatigue
      development.

PMID- 30210097
TI  - The effect of lead (Pb) exposure and iron (Fe) deficiency on intestinal
      lactobacilli, E. coli and yeast: A study in experimental rats.
AB  - OBJECTIVE: The current study investigated the additive effect of oral lead (Pb)
      exposure and dietary iron (Fe) deficiency on intestinal lactobacilli, E. coli,
      and yeast in SD rats. METHODS: Weanling rats were fed on control diet (CD) or
      iron deficient diet (ID) for 4 weeks, followed by oral Pb exposure for another 4
      weeks. Lead exposure was withdrawn for 2 weeks, and then resumed after 2 weeks.
      Blood samples were collected to determine haemoglobin (Hb), serum iron, blood Pb
      and delta-Aminolevulenic acid dehydratase (ALAD) activity. Fecal samples were
      collected to enumerate the lactobacilli, E. coli and yeast population on
      selective agar media and determine Pb levels. RESULTS: Hb and serum Fe levels
      decreased significantly in iron deficient rats. Pb exposed rats had a significant
      increase in blood Pb levels and decreased ALAD activity. The lactobacilli
      population was significantly decreased (p<0.05) in ID rats compared to the CD
      group. Further, a significant decrease in the lactobacilli population was
      observed in Pb exposed rats irrespective of the dietary regimen. Upon withdrawal
      of Pb exposure, lactobacilli increased significantly in both the CD+Pb and ID+Pb
      groups, whereas re-exposure to Pb decreased lactobacilli population. The E. coli
      and yeast populations were inconsistent among both the ID and Pb exposed rats
      compared to controls. Fecal Pb levels increased significantly in Pb exposed rats
      irrespective of diet. CONCLUSION: An additive effect of dietary Fe deficiency and
      oral Pb exposure resulted in greater reductions in the intestinal lactobacilli
      population compared to either treatment alone. In addition, transient withdrawal
      of Pb exposure led to improved lactobacilli population irrespective of Fe status.

PMID- 30210098
TI  - Frequency of firefighters' heat-related illness and its association with removing
      personal protective equipment and working hours.
AB  - The purpose of this study was to examine the frequency of firefighters' heat
      related illness (HRI) in the line of duty with relation to resting/working hours
      and the behaviour of taking off PPE during rest periods based on nationwide
      survey (N=674). The results showed that 74.8% of firefighters experienced HRI
      symptoms and 5% of firefighters suffered from symptoms of HRI 20 times or more in
      a year. This study also showed a statistically significant correlation between
      working hours and removing PPE with the experience of HRI symptoms (P<0.05). In
      addition, removing PPE except the helmet was correlated with resting hours
      (P<0.001; Gloves: P=0.051), which indicates removing PPE is related to resting
      time. This study revealed that firefighters routinely experienced mild HRI
      symptoms and the fatalities were just a tiny fraction. It is also emphasized that
      attention should be given on the significant role of taking off PPE during rest
      and on the standardized firefighters' rehabilitation followed by its application.

PMID- 30210100
TI  - A Low Early High-density Lipoprotein Cholesterol Level is an Independent
      Predictor of In-hospital Death in Patients with Acute Coronary Syndrome.
AB  - Objective In patients with acute coronary syndrome (ACS), low high-density
      lipoprotein cholesterol (HDL-C) levels in samples collected after an overnight
      fast are diagnostic indicators and well-established predictors of adverse
      outcomes. However, the relationship between the HDL-C levels in samples collected
      just after arrival (early HDL-C) and in-hospital mortality remains unknown. The
      purposes of the present ACS study were to (1) evaluate the association between
      the early HDL-C levels of patients and in-hospital mortality and (2) compare the
      early HDL-C level with other well-known determinants associated with in-hospital
      mortality. Methods This retrospective study surveyed 638 consecutive ACS patients
      and then assessed the possible determinants of in-hospital mortality. All initial
      blood samples, including that for early HDL-C, were drawn within one hour of
      arrival. Results In the present study, the overall in-hospital mortality was
      5.9%. A multivariable analysis showed that a low early HDL-C (odds ratio [OR]
      2.53, 95% confidence interval [CI] 1.14-5.62), elevated troponin T (OR 4.40, 95%
      CI 1.26-15.29) and high Killip class (OR 15.41, 95% CI 7.29-32.59) were
      independent predictors of in-hospital mortality. A Kaplan-Meier survival analysis
      indicated that there the in-hospital outcome for the low early HDL-C group was
      significantly worse than that for the high early HDL-C group (age- and gender
      adjusted hazard ratio 2.40, 95% CI 1.15-5.00, p=0.02). Conclusion ACS patients
      with low early HDL-C levels had higher in-hospital mortalities than those who did
      not have low early HDL-C levels. In addition to the already well-known
      determinants, low early HDL-C should also be considered as an independent
      predictor of in-hospital mortality in ACS patients who present to a cardiac care
      unit.

PMID- 30210101
TI  - Differences in Adherence Barriers to Inhaled Medicines between Japanese Patients
      with Chronic Obstructive Pulmonary Disease and Asthma Evaluated using the
      "Adherence Starts with Knowledge 20" (ASK-20) Questionnaire.
AB  - Objective This multicenter, cross-sectional, non-interventional trial aimed to
      investigate adherence barriers to inhaled medicines when compared with oral
      medicines in Japanese patients with chronic obstructive pulmonary disease (COPD)
      and asthma. Methods The self-reporting "Adherence Starts with Knowledge 20" (ASK
      20) questionnaire was administered for adherence barriers of inhaled and oral
      medicines to outpatients with regular clinic attendance. Results Patients with
      COPD and asthma reported different adherence barriers to inhaled medicines.
      Independent adherence barriers (odds ratio [95% confidence interval]) to inhaled
      medicines relative to those for oral medicines among patients with COPD and
      asthma were those related to item Q8 ( "I know if I am reaching my health goals";
      2.49 [1.39-4.47]; p=0.0022) and item Q2 ( "I run out of my medicine because I do
      not get refills on time"; 2.69 [1.26-5.75]; p=0.0127), respectively. Among
      patients with poor adherence to only inhaled medicines, those with COPD and
      asthma recognized item Q3 ( "consuming alcohol and taking medicines"; 6.63 [1.27
      34.7]; p<0.05) and item Q1 ( "forget to take medicines only sometimes"; 4.29
      [1.83-10.0]; p<0.05), respectively, were recognized as independent adherence
      barriers to inhaled medicines. The total ASK-20 scores and total barrier counts
      in patients with poor adherence to inhaled medicines were significantly higher
      than in those without poor adherence among patients with asthma (p=0.0057) but
      not those with COPD (p>0.05). Conclusion These results will aid in personalizing
      education on adherence to inhaled medicines among patients with COPD and asthma.

PMID- 30210099
TI  - G3 PhyloChip Analysis Confirms the Promise of Plant-Based Culture Media for
      Unlocking the Composition and Diversity of the Maize Root Microbiome and for
      Recovering Unculturable Candidate Divisions/Phyla.
AB  - The rapid development of high-throughput techniques and expansion of bacterial
      databases have accelerated efforts to bring plant microbiomes into cultivation.
      We introduced plant-only-based culture media as a successful candidate to mimic
      the nutritional matrices of plant roots. We herein employed a G3 PhyloChip
      microarray to meticulously characterize the culture-dependent and -independent
      bacterial communities of the maize root compartments, the endo- and ecto
      rhizospheres. An emphasis was placed on the preference of the growth of
      unculturable candidate divisions/phyla on plant-only-based culture media over
      standard culture media (nutrient agar). A total of 1,818 different operational
      taxonomic units (OTUs) were resolved representing 67 bacterial phyla. Plant-only
      based culture media displayed particular affinity towards recovering endophytic
      over ectophytic rhizobacteria. This was shown by the slightly higher recovery of
      CFUs for endophytes on plant-only-based culture media (26%) than on standard
      culture media (10%) as well as the higher taxa richness and numbers of exclusive
      families of unculturable divisions/phyla. Out of 30 bacterial phyla (comprising
      >95% of the whole population), 13 were of a significantly higher incidence on
      plant-only-based culture media, 6 phyla of which were not-yet-cultured
      (Atribacteria, OP9; Dependentiae, TM6; Latescibacteria, WS3; Marinimicrobia,
      SAR406; Omnitrophica, OP3; BRC1). Furthermore, plant-only-based culture media
      significantly enriched less abundant and/or hard-to-culture bacterial phyla
      (Acidobacteria, Gemmatimonadetes, and Tenericutes). These results present
      conclusive evidence of the ability of plant-only-based culture media to bring the
      plant-fed in situ microbiome into the status of plant-fed in vitro cultures, and
      to widen the scope of cultivation of heretofore-unculturable bacterial
      divisions/phyla.

PMID- 30210102
TI  - Aortic Mural Thrombus in the Non-Atherosclerotic Aorta of Patients with Multiple
      Hypercoagulable Factors.
AB  - An aortic mural thrombus (AMT) on a non-atherosclerotic wall is a rare but
      important cause of arterial thromboembolism. We herein report two cases of AMT in
      the thoracic aorta. Both showed multiple hypercoagulable factors (case 1: protein
      S deficiency and positive finding of anti-cardiolipin antibody; case 2: protein C
      deficiency, gastric cancer, and cisplatin-based chemotherapy) and were
      successfully treated with anticoagulation. Hypercoagulable states, including
      malignancy, can influence the formation of AMT; therefore, the accurate
      assessment of a hypercoagulable condition is necessary when we encounter patients
      with AMT.

PMID- 30210103
TI  - The Effectiveness of Cost Reduction with Charge Displays on Test Ordering under
      the Health Insurance System in Japan: A Study Using Paper-based Simulated Cases
      for Residents and Clinical Fellows.
AB  - Objective To determine whether or not displaying the cost of tests can help
      reduce charges on test ordering in Japan. Methods This study was conducted under
      the setting of a simulated first visit of an outpatient for general internal
      medicine in a secondary medical institution in Japan. We randomly assigned 27
      residents and clinical fellows to Team A or B. The first half, without charges
      displayed on the ordering system, was designated the "non-display group," and the
      participants of Team A selected tests for each paper-based simulated case (Q1
      Q14), while the participants of Team B selected tests for Q15-Q28. The second
      half, which had charges displayed, was designated the "display group," and the
      participants of Team A selected tests for Q15-Q28, while the participants of Team
      B selected tests for Q1-Q14. The main outcome measure was the difference in the
      cost of tests per paper-based simulated case between the non-display and display
      groups. Results The median (interquartile range) cost of tests per paper-based
      simulated case was 12,255 yen (5,040-23,695 yen) in the non-display group versus
      9,425 yen (2,320-21,700 yen) in the display group, showing a decrease of 2,830
      yen with charges being displayed (p=0.002). Conclusion Displaying the charges
      when ordering tests in paper-based simulated cases resulted in cost reduction.
      The adoption of this intervention may reduce health insurance costs under the
      health insurance system in Japan, which has features such as universal health
      coverage and universal access to care.

PMID- 30210104
TI  - Severe Community-acquired Pneumonia Caused by Acinetobacter baumannii
      Successfully Treated with the Initial Administration of Meropenem Based on the
      Sputum Gram Staining Findings: A Case Report.
AB  - A 62-year-old man with diabetes mellitus and a two-day history of fever and
      dyspnea presented at our hospital. He was diagnosed with community-acquired
      pneumonia (CAP), septic shock, and respiratory failure. Sputum Gram staining
      revealed Gram-negative coccobacilli. Based on the Gram staining findings and
      history, Acinetobacter baumannii was considered as one of the causative organisms
      of his CAP. Consequently, he was successfully treated with the initial
      administration of meropenem. We suggest that A. baumannii should be considered as
      one of the possible causative organisms of CAP based on a fulminant clinical
      course, and the presence of Gram-negative coccobacilli.

PMID- 30210105
TI  - A Case of Bilateral Adrenocortical Adenomas along with Virilization and Cushing's
      Syndrome.
AB  - We herein present the case of a 27-year-old woman with clinical and biochemical
      features of virilism. Imaging studies revealed the presence of a bilateral
      adrenal tumor. Although the secretion of androgens was remarkable, the autonomous
      production of cortisol was also evident because of a loss of circadian rhythm and
      the absence of cortisol suppression by dexamethasone. The surgical excision of
      both adrenal tumors was performed, and the histological examination showed no
      malignancy. We also report the successful pregnancy and delivery of the patient
      who showed evolving adrenocortical insufficiency along with virilization and
      Cushing' s syndrome and who continued to receive glucocorticoid replacement
      therapy during pregnancy.

PMID- 30210106
TI  - Acute Unilateral Isolated Oculomotor Nerve Palsy in an Adult Patient with
      Influenza A.
AB  - An otherwise healthy 44-year-old woman exhibited isolated unilateral oculomotor
      nerve palsy accompanied by an influenza A infection. An intra-orbital MRI scan
      revealed that her right third intracranial nerve was enlarged and enhanced. She
      recovered completely during the first month after treatment with oseltamivir
      phosphate. Although intracranial nerve disorders that result from influenza
      infections are most frequently reported in children, it is noteworthy that
      influenza can also cause focal intracranial nerve inflammation with
      ophthalmoparesis in adults. These disorders can be diagnosed using intra-orbital
      MRI scans with appropriate sequences and through immunological assays to detect
      the presence of antiganglioside antibodies.

PMID- 30210107
TI  - A Rare Case of Klinefelter Syndrome Accompanied by Spastic Paraplegia and
      Peripheral Neuropathy.
AB  - Klinefelter syndrome is a chromosomal disorder with a typical karyotype of 47,
      XXY, accompanied by various neurological symptoms. We herein report the first
      case of Klinefelter syndrome with a rare mosaic form of 47, XXY and 48, XXXY,
      combined with both spastic paraplegia and peripheral motor neuropathy. This case
      showed spasticity and hyperreflexia with pathological reflexes and ankle clonus
      as well as muscle weakness in all extremities. A motor nerve conduction study and
      the magnetic motor evoked potential suggested motor axonal neuropathy and
      corticospinal tract disorders. The present case suggests that Klinefelter
      syndrome can present with both upper and lower motor neuron degeneration.

PMID- 30210108
TI  - Lipoprotein Lipase Deficiency Arising in Type V Dyslipidemia.
AB  - A 40-year-old Japanese man presented with child-onset hypertriglyceridemia
      recently complicated by diabetes mellitus. The patient's diabetes mellitus was
      maintained, but he had persistent insulin resistance. The patient also had
      persistent severe hypertriglyceridemia (1,224-4,104 mg/dL), despite the
      administration of bezafibrate and ezetimibe. Type V dyslipidemia was revealed by
      agarose gel electrophoresis and the refrigerator test, and a significantly
      reduced post-heparin lipoprotein lipase mass of 26 ng/mL was confirmed. Genetic
      testing confirmed two heterozygous LPL variants, p.Tyr88X and p.Gly215Glu in
      trans; thus, the patient was diagnosed with lipoprotein lipase deficiency.
      Lipoprotein lipase deficiency typically arises in type I dyslipidemia, but is
      latent in type V dyslipidemia.

PMID- 30210109
TI  - A Case of a Small Cell Lung Cancer Patient with Anti-transcriptional Intermediary
      Factor 1gamma Antibody Who Developed Dermatomyositis after Successful
      Chemoradiotherapy.
AB  - We herein report a 63-year-old woman with small-cell lung cancer (SCLC) who
      developed dermatomyositis (DM) after initial chemoradiotherapy despite tumor
      reduction. Serum anti-TIF1gamma antibody was detected before the development of
      DM, and its levels increased over time. She died five months after the diagnosis
      of SCLC. Anti-TIF1gamma antibody is known to be a marker for cancer-associated DM
      (CAM); however, the present case indicates that the antibody can be found in
      cancer patients without DM. This case is also unusual, as DM developed later
      despite successful chemoradiotherapy. (86 words <100).

PMID- 30210110
TI  - A Case of Persistent Vegetative State after Diabetic Ketoacidosis Triggered by an
      Overdose of Psychotropic Agents.
AB  - A 28-year-old man with type 1 diabetes mellitus was admitted for shock and coma
      due to diabetic ketoacidosis. Despite aggressive treatment and management of the
      patient's underlying clinical issues, the patient remained in a comatose state.
      Further investigations revealed an excess consumption of psychotropic agents;
      however, there was no evidence of an insulin overdose. Physicians should be aware
      that, in patients who are highly dependent upon insulin, an overdose of
      psychotropic agents can lead to hypoxic-ischemic brain injury.

PMID- 30210111
TI  - Support for Patients who have Difficulty Quitting Smoking: A Review.
AB  - Smoking cessation plays a crucial role in reducing preventable morbidity and
      mortality. However, some smokers find smoking cessation difficult, despite
      receiving treatment. This includes heavy smokers with chronic obstructive
      pulmonary disease, smokers with a psychiatric disorder, and female and underage
      smokers. This review article describes smoking cessation approaches for patients
      who find it difficult to quit smoking.

PMID- 30210112
TI  - Endoscopic Submucosal Dissection for Gastric-phenotype Adenoma on the Surface of
      Gastric Gastrointestinal Stromal Tumor.
AB  - We herein report a rare case of a gastric adenoma overlying a gastrointestinal
      stromal tumor (GIST) that was removed by endoscopic submucosal dissection (ESD).
      A 78-year-old woman was referred to our hospital. Esophagogastroduodenoscopy
      revealed an elevated lesion of 15 mm in diameter overlying a submucosal mass in
      the gastric cardia. ESD was performed for the epithelial neoplasm, and biopsy
      specimens were obtained directly from the exposed surface of the submucosal
      tumor. The epithelial tumor was a tubular adenoma with focal severe atypia and a
      gastric phenotype. Biopsy specimens revealed a GIST, which was resected by
      laparoscopic intragastric surgery afterward.

PMID- 30210113
TI  - Headache due to Spontaneous Spinal Cerebrospinal Fluid Leaks.

PMID- 30210114
TI  - A Case of Intratumoral Hemorrhage of Liver Metastasis from a Rectal
      Neuroendocrine Tumor.
AB  - A 56-year-old healthy woman was referred to our hospital for abdominal pain.
      Contrast-enhanced computed tomography (CT) showed a 14-cm-diameter liver tumor
      with intratumoral hemorrhage. We performed emergent transcatheter arterial
      embolization. She was referred to hepatic surgeon (M.M.) for resection.
      Preoperative colonoscopy showed an elevated lesion measuring 2 cm in diameter
      that was pathologically diagnosed as a rectal neuroendocrine tumor (NET). We
      performed low anterior resection of the rectum, followed by extended right
      hepatectomy for all hepatic lesions. Intratumoral hematoma was observed in the
      largest hepatic lesion (size: 150 mm*100 mm). Microscopy also indicated NET G2.
      We pathologically diagnosed a liver tumor from a rectal NET that bled
      spontaneously.

PMID- 30210115
TI  - Randomized Controlled Trial Comparing the Effects of Vonoprazan Plus Rebamipide
      and Esomeprazole Plus Rebamipide on Gastric Ulcer Healing Induced by Endoscopic
      Submucosal Dissection.
AB  - Objectives Gastric endoscopic submucosal dissection (ESD) is currently a standard
      procedure, and proton pump inhibitors (PPIs) are most commonly used to treat post
      ESD ulcers. Vonoprazan, a potassium-competitive acid blocker (P-CAB), reportedly
      inhibits gastric acid secretions more effectively than PPIs. Combination therapy
      of a PPI plus rebamipide is effective for treating larger ulcers. Our goal was to
      evaluate the effects of vonoprazan plus rebamipide compared to esomeprazole plus
      rebamipide for the treatment of post-ESD ulcers. Methods First, vonoprazan plus
      rebamipide (V group) or esomeprazole plus rebamipide (E group) was orally
      administered to subjects for eight weeks. We then evaluated the ulcer healing
      process at four and eight weeks after the procedure using a gastric ulcer stage
      system and by measuring the ulcer size. Patients A total of 84 patients who
      underwent ESD for gastric neoplasms between September 2015 and December 2017 in
      Tsuchiura Kyodo General Hospital were included in this randomized controlled
      trial. Results The ulcer scar rates at week 4 in the V group (n=43) and E groups
      (n=39) were 20.9% and 15.4%, while those at week 8 were 90.7% and 92.3%,
      respectively. The ulcer reduction rates at week 4 in the V and E groups were
      94.6% and 93.8%, and those at week 8 were 99.7% and 99.3%, respectively. The
      ulcer scar rates and reduction rates were not significantly different between the
      two groups. Conclusion Combination therapy consisting of vonoprazan plus
      rebamipide was not superior to that of esomeprazole plus rebamipide for post-ESD
      ulcer healing (UMIN000019516).

PMID- 30210117
TI  - A Rare Form of Intraductal Papillary Mucinous Carcinoma.

PMID- 30210118
TI  - Mandibular Herpes Zoster.

PMID- 30210119
TI  - Fatal Chronic Active Epstein-Barr Virus Infection in a Rheumatoid Arthritis
      Patient Treated with Abatacept.
AB  - Chronic active Epstein-Barr virus (CAEBV) T-cell type infection, systemic form,
      is characterized by persistent infectious mononucleosis-like symptoms, high EBV
      DNA levels in the peripheral blood, organ damage, and a poor prognosis. The
      association between CAEBV and rheumatoid arthritis (RA) is unclear. We report a
      case of fatal CAEBV T-cell type infection in an RA patient undergoing treatment
      with cytotoxic T-lymphocyte-associated antigen 4 immunoglobulin fusion protein
      (abatacept, ABT). CAEBV can rapidly worsen in RA patients receiving ABT. Thus, we
      should try to establish an early diagnosis in patients with CAEBV infection.

PMID- 30210116
TI  - Atypical Clinical Presentation of Crohn's Disease with Superior Mesenteric Vein
      Obstruction and Protein-losing Enteropathy.
AB  - We herein report a 44-year-old man suffering from systemic edema due to protein
      losing enteropathy (PLE) with superior mesenteric vein (SMV) obstruction and
      development of collateral veins, which subsequently proved to be a chronic result
      of thrombosis and a complication of Crohn's disease (CD). PLE was supposedly
      induced by both intestinal erosion and thrombosis-related lymphangiectasia, which
      was histologically proven in his surgically-resected ileal stenosis. Elemental
      diet and anti-TNFalpha agent improved his hypoalbuminemia after surgery. The
      rarity of the simultaneous coexistence of SMV obstruction and PLE and the
      precedence of these complications over typical abdominal symptoms of CD made the
      clinical course complex.

PMID- 30210120
TI  - Hereditary Hemorrhagic Telangiectasia with SMAD4 Mutations is Associated with
      Fatty Degeneration of the Left Ventricle, Coronary Artery Aneurysm, and Abdominal
      Aortic Aneurysm.
AB  - A 52-year-old man with recurrent epistaxis and palpebral conjunctival
      telangiectasia visited our hospital for a follow-up checkup for gastrointestinal
      polyposis. At 48 years of age, he underwent Y-graft replacement for an abdominal
      aortic aneurysm. Arteriovenous malformation (AVM) was detected in his lungs, and
      a genetic test revealed an SMAD4 mutation. Eventually, he was diagnosed with
      juvenile polyposis-hereditary hemorrhagic telangiectasia (JP-HHT) syndrome. In
      addition, fatty degeneration of the left ventricle (LV) and a coronary aneurysm
      were detected. This is the first report suggesting the possibility of an
      association between these manifestations and JP-HHT due to SMAD4 mutations.
      Examining cardiovascular disorders in JP-HHT patients is imperative.

PMID- 30210121
TI  - Auricle Pain Due to Tophi.

PMID- 30210122
TI  - Association between Functional Dyspepsia and Gastric Depressive Erosions in
      Japanese Subjects.
AB  - Objective The association between functional dyspepsia (FD) and endoscopic
      findings has not been fully elucidated. Helicobacter pylori infection is
      considered a key factor in the pathophysiology of FD. The Kyoto Classification of
      Gastritis (KCG) was proposed in 2014 to evaluate endoscopic findings based on the
      H. pylori status. We investigated the endoscopic findings associated with FD
      according to the KCG. Methods This cross-sectional study included subjects who
      underwent esophagogastroduodenoscopy during a medical health check-up. We
      compared the endoscopic findings between subjects with FD and healthy controls
      (HCs) according to the KCG. Results A total of 456 subjects were analyzed. Among
      them, the detection rate of FD was 5.5% (25/456 persons). In a univariate
      analysis of the endoscopic findings, a significantly lower proportion of subjects
      with FD had gastric red streak in comparison to HCs (0% vs. 18.6%, respectively;
      p=0.0124). Subjects with FD were more likely to have gastric depressive erosion
      (20.0% vs. 7.9%; p=0.0522). A higher proportion of the erosion-positive subjects
      had FD in comparison to erosion-negative subjects (12.8% vs. 4.8%). There were no
      significant differences in the other endoscopic findings, including gastric
      atrophy, intestinal metaplasia, enlarged fold, nodularity, and diffuse redness. A
      multivariate analysis revealed that gastric depressive erosion was significantly
      and independently associated with FD (odds ratio, 2.92; 95% confidence interval,
      1.03-8.26; p=0.0436). In contrast, gastric red streak was not associated with FD
      (p=0.989). Conclusion Gastric depressive erosions may be associated with
      dyspepsia.

PMID- 30210124
TI  - Transient Diffusion-weighted Imaging Hyperintensity of the Cerebellar Cortex in
      Paraneoplastic Cerebellar Degeneration.

PMID- 30210123
TI  - An analysis of the biological disease-modifying antirheumatic drug-free condition
      of adalimumab-treated rheumatoid arthritis patients.
AB  - Objectives The present study was performed with the aim of analyzing the
      biological disease-modifying antirheumatic drug (bDMARD)-free (Bio-free)
      condition of adalimumab (ADA)-treated rheumatoid arthritis (RA) patients in a
      real-world setting. Methods ADA was used in the treatment of 130 (male, n=21;
      female, n=109 females) RA patients. Among them, 26 patients (20.0%) discontinued
      ADA due to a good response. We analyzed 20 patients who were followed up for more
      than 6 months after the discontinuation of ADA. The Disease Activity Score 28
      based on C-reactive protein (DAS28-CRP) and modified health assessment
      questionnaires (mHAQs) were evaluated. Results The mean age of the patients was
      53.4+/-11.1 years. The mean disease duration was 4.5+/-4.3 years. Sixteen
      patients were bDMARD-naive, while 4 switched from bDMARDs to ADA. At 6 months
      after the discontinuation ADA, 19 patients had achieved a clinical remission, and
      1 had achieved a low disease activity. The Bio-free period was 26.4+/-15.5
      months. The dose of prednisolone was significantly reduced from baseline (3.45+/
      3.17 mg/day) at 6 months after the discontinuation of ADA (2.63+/-2.78 mg/day).
      The dose of methotrexate was unchanged. The number of conventional synthetic
      DMARDs (csDMARDs) was significantly increased (0.8+/-0.6 to 1.4+/-1.06). The mHAQ
      values were significantly ameliorated by ADA and remained good in patients with a
      Bio-free condition. A multivariate analysis showed that the dose of MTX was an
      important factor for achieving a Bio-free condition. Conclusions A sustainable
      Bio-free condition in a real clinical setting can be achieved and may be a
      suitable way of reducing medical costs. The dose of MTX and the additional
      administration of csDMARDs is therefore thought to be important for ensuring a
      good outcome in these patients.

PMID- 30210125
TI  - A Case of Nutcracker Syndrome with the Superimposition of Thin Basement Membrane
      Syndrome.
AB  - A 21-year-old woman was referred to our hospital because of proteinuria and
      hematuria. She had occasional flank pain. A renal biopsy was performed and
      revealed a thin basement membrane. Therefore, she was diagnosed with thin
      basement membrane disease. However, the frequency of her flank pain increased.
      Since her left kidney was slightly larger than the right, nutcracker syndrome
      (NCS) was suspected. Renal vein ultrasonography and venography were performed,
      and NCS was confirmed. Her hematuria was multifactorial, and NCS can go unnoticed
      if there is a comorbidity that also causes hematuria.

PMID- 30210126
TI  - Pulmonary Multiloculated 'Lotus Torus-like' Sarcoidosis Mimicking Lung
      Adenocarcinoma.
AB  - A 34-year-old Japanese woman exhibited a 35*25-mm solitary multiloculated mass
      shadow in the left lower lobe mimicking lung adenocarcinoma. On computed
      tomography, the mass resembled a lotus torus. A transbronchial lung biopsy and
      mediastinal lymph node biopsy led to the diagnosis of sarcoidosis. This lotus
      torus-like mass regressed spontaneously. This is the second reported case of
      pulmonary cavitary sarcoidosis with a 'lotus torus-like' appearance. We propose
      several findings regarding the lotus torus-like appearance by comparing the
      findings to those of lung adenocarcinoma. Knowledge of this unique sign may be
      helpful for the differential diagnosis of pulmonary sarcoidosis from lung
      adenocarcinoma.

PMID- 30210127
TI  - Yellow Nail Syndrome Patients with Diffuse Panbronchiolitis-like pulmonary
      manifestation: Two case reports.
AB  - Yellow nail syndrome (YNS) is a rare clinical syndrome characterized by a triad
      of yellow thick nail, lymphedema and respiratory diseases. We experienced 2 cases
      of YNS with diffuse panbronchiolitis (DPB)-like pulmonary manifestation. Since
      YNS might be hidden to those who have been diagnosed with DPB, physicians should
      be alert to recognize nail signs of YNS in case of DPB refractory to macrolide
      therapy. We hereby review previous case reports of YNS and discuss its pulmonary
      manifestations.

PMID- 30210128
TI  - Foix-Chavany-Marie Syndrome Induced by a Unilateral Brain Abscess.
AB  - Foix-Chavany-Marie syndrome (FCMS) is a rare cortical type of pseudobulbar palsy
      characterized by the loss of voluntary control of the facial, pharyngeal,
      lingual, and masticatory muscles with preserved reflexive and autonomic
      functions. FCMS is generally associated with cerebrovascular diseases affecting
      the bilateral opercular regions. We herein report the clinical features of an 84
      year-old right-handed Japanese man with FCMS due to a unilateral brain abscess.
      The patient' s symptoms were resolved after treating the brain abscess. The
      present clinical results suggest that a unilateral brain abscess in the temporal
      operculum with a persistent old lesion in the contralateral insular cortex can
      induce FCMS.

PMID- 30210129
TI  - Development of Pulmonary Arterial Hypertension in a Patient Treated with Qing-Dai
      (Chinese Herbal Medicine).
AB  - Pulmonary arterial hypertension (PAH) is a rare, devastating disease,
      characterized by elevated pulmonary arterial pressure due to pulmonary
      microvascular obstruction, which can result in heart failure and death. PAH can
      be associated with exposure to certain drugs or toxins. We herein report a case
      in which PAH developed in a patient with refractory ulcerative colitis (UC)
      during treatment with "Qing-Dai," a Chinese herbal medicine. The patient's PAH
      improved after the discontinuation of Qing-Dai.

PMID- 30210131
TI  - Hepatitis B Virus Reactivation in a Patient with Nonalcoholic Steatohepatitis 41
      Months after Rituximab-containing Chemotherapy: A Case Report.
AB  - Hepatitis B virus (HBV) reactivation occasionally occurs long after
      immunosuppressive therapy. The characteristics of late HBV reactivation remain
      unclear. We herein present a case of HBV reactivation in a patient with
      nonalcoholic steatohepatitis (NASH) more than 3 years after rituximab-containing
      chemotherapy for diffuse large B-cell lymphoma. Increased transaminase levels,
      which were induced by NASH, were observed after chemotherapy and were alleviated
      with statin treatment. HBV reactivation was identified incidentally. The patient
      developed hepatitis that improved with entecavir therapy. Our case might indicate
      that the presence of NASH is associated with HBV reactivation long after
      treatment and that statins, as immune-modulatory agents, affect HBV reactivation.

PMID- 30210130
TI  - The Hypercholesterolemia Paradox in Percutaneous Coronary Intervention: An
      Analysis of a Multicenter PCI Registry.
AB  - Objectives The aim of this study was to assess the relationship between
      hypercholesterolemia (HC) and clinical events through a percutaneous coronary
      intervention (PCI) registry. Background HC is a well-known independent risk
      factor for long-term cardiovascular events after PCI. However, it has been
      reported to be associated with a lower risk of adverse events in patients with
      cancer or acute coronary syndrome. Methods We analyzed the relationship between
      HC and adverse events in patients treated with everolimus-eluting stents (EESs)
      through the Tokyo-MD PCI study (an all-comer, multicenter, observational
      registry). The propensity score method was applied to select two groups with
      similar baseline characteristics. Results The unadjusted population included
      1,536 HC patients and 330 non-HC patients. Propensity score matching yielded 314
      matched pairs. After baseline adjustment, the outcomes of HC patients were
      significantly better than those of the non-HC patients with respect to the
      primary endpoint, which was a combination of mortality from all causes, nonfatal
      myocardial infarction (MI), nonfatal neurological events, and major bleeding
      (hazard ratio [HR] 0.56, 95% confidence interval [CI] 0.39-0.81; p=0.002), and
      the secondary endpoints, which included a combination of mortality from all
      causes, nonfatal MI, and nonfatal neurological events (HR 0.59, 95% CI 0.39-0.88;
      p=0.01), and major bleeding (HR 0.42, 95% CI 0.20-0.88; p=0.02). A subgroup
      analysis showed age as an interaction factor for the primary endpoint
      (interaction p=0.035). Conclusion HC was associated with better outcomes in
      patients who underwent EES implantation, even after baseline adjustment.

PMID- 30210132
TI  - Disseminated Nocardiosis Initially Manifesting as Visual Field Defects.

PMID- 30210133
TI  - Ureteropelvic Junction Obstruction Underlying Pyelonephritis in an Adult.

PMID- 30210134
TI  - Gemcitabine, Dexamethasone, and Cisplatin Regimen as an Effective Salvage Therapy
      for High-grade B-cell Lymphoma with MYC and BCL2 and/or BCL6 Rearrangements.
AB  - A 61-year-old woman exhibited right inguinal lymphadenopathy and right lower limb
      edema approximately 1 month prior to hospitalization. She was diagnosed with high
      grade B-cell lymphoma, and a lymph node biopsy and fluorescence in situ
      hybridization indicated MYC, BCL2, and BCL6 rearrangements (triple-hit lymphoma).
      She had progressive disease that was CD20-negative after two courses of R-CODOX
      M/IVAC therapy. Subsequent EPOCH therapy was not effective. However, after two
      cycles of gemcitabine, dexamethasone, and cisplatin (GDP) therapy, she achieved a
      complete response and was able to undergo autologous peripheral blood stem cell
      transplantation. GDP therapy may be effective as salvage therapy for chemotherapy
      resistant triple-hit lymphoma.

PMID- 30210135
TI  - Hemodynamic and Hormonal Effects of Tolvaptan for Heart Failure.
AB  - Tolvaptan (TLV) is a diuretic agent administrated for heart failure (HF) only in
      Japan. Many clinical findings have been obtained from the accumulation of
      clinical experience, and the administration of TLV reportedly avoids causing a
      reduction in the renal function. In addition, TLV has been reported to exert
      effects other than diuresis. The early start of TLV after hospitalization
      shortens the length of the hospital stay, and continuous TLV after discharge
      extends the period until re-hospitalization of HF patients. TLV is thought to
      function via vasopressin V2 receptor antagonism. However, no significant
      differences in the long-term prognosis were noted between the group using TLV and
      not using TLV in the EVEREST trial, and effects other than diuresis are not
      useful for all HF patients. Therefore, it is necessary to identify patients who
      may experience effects other than diuresis with TLV administration. The
      accumulation of more patients and findings from further large-scale clinical
      trials will be necessary in order to clarify these points.

PMID- 30210136
TI  - Ruptured Baker's Cyst in Rheumatoid Arthritis.

PMID- 30210137
TI  - Hereditary Angioedema from 1888 to 2018 -Progress and Problems.

PMID- 30210139
TI  - Number of Board-Certified Cardiologists and Acute Myocardial Infarction-Related
      Mortality in Japan - JROAD and JROAD-DPC Registry Analysis.
AB  - BACKGROUND: The appropriate number of board-certified cardiologists (BCC) for the
      treatment of acute myocardial infarction (AMI) has not been thoroughly examined
      in Japan. This study investigated whether the number of BCC/50 cardiovascular
      beds affects acute outcome in AMI treatment. Methods and Results: Data on 751
      board-certified teaching hospitals and 63,603 patients with AMI were obtained
      from the Japanese Registry Of All cardiac and vascular Diseases (JROAD) and JROAD
      Diagnosis Procedure Combination (JROAD-DPC) databases between 1 April 2012 and 31
      March 2014. The hospitals were categorized into 3 groups based on the median
      number of BCC/50 cardiovascular beds: first tertile, 5.0 (IQR, 4.0-5.7); second,
      8.3 (IQR, 7.4-9.8); third, 15.3 (IQR, 12.5-22.7), and the patients with AMI
      admitted to the categorized hospitals were compared (first tertile, 12,002
      patients; second, 23,930; third, 27,671). On hierarchical logistic modeling, the
      adjusted OR for 30-day mortality were 0.86 (95% CI: 0.74-1.00) for the second
      tertile and 0.75 (95% CI: 0.65-0.88) for the third tertile. CONCLUSIONS: Patients
      with AMI admitted to hospitals with a large number of BCC/50 cardiovascular beds
      had a lower 30-day mortality rate. This tendency was independent of patient and
      hospital characteristics. This is the first study to provide new information on
      the association between the number of BCC and in-hospital AMI-related mortality
      in Japan.

PMID- 30210138
TI  - Smoking, Smoking Cessation, and Risk of Mortality in a Japanese Working
      Population - Japan Epidemiology Collaboration on Occupational Health Study.
AB  - BACKGROUND: The effect of smoking on mortality in working-age adults remains
      unclear. Accordingly, we compared the effects of cigarette smoking and smoking
      cessation on total and cause-specific mortality in a Japanese working population.
      Methods and Results: This study included 79,114 Japanese workers aged 20-85 years
      who participated in the Japan Epidemiology Collaboration on Occupational Health
      Study. Deaths and causes of death were identified from death certificates, sick
      leave documents, family confirmation, and other sources. Hazard ratios (HRs) and
      95% confidence intervals (CIs) were estimated via Cox proportional hazards
      regression. During a maximum 6-year follow-up, there were 252 deaths in total.
      Multivariable-adjusted HRs (95% CIs) for total mortality, cardiovascular disease
      (CVD) mortality, and tobacco-related cancer mortality were 1.49 (1.10-2.01), 1.79
      (0.99-3.24), and 1.80 (1.02-3.19), respectively, in current vs. never smokers.
      Among current smokers, the risks of total, tobacco-related cancer, and CVD
      mortality increased with increasing cigarette consumption (Ptrend<0.05 for all).
      Compared with never smokers, former smokers who quit <5 and >=5 years before
      baseline had HRs (95% CIs) for total mortality of 1.80 (1.00-3.25) and 1.02 (0.57
      1.82), respectively. CONCLUSIONS: In this cohort of workers, cigarette smoking
      was associated with increased risk of death from all and specific causes
      (including CVD and tobacco-related cancer), although these risks diminished 5
      years after smoking cessation.

PMID- 30210140
TI  - Complexity of Antibiotic Resistance in Commensal Escherichia coli Derived from
      Pigs from an Intensive-Production Farm.
AB  - Antibiotics in animal husbandry are used to maintain welfare, but lead to the
      generation of resistant strains. We analyzed commensal multidrug-resistant
      Escherichia coli from pigs at the beginning and end of the production cycle in a
      farm with a farrow-to-finish system in order to investigate whether clonal spread
      or horizontal gene transfer constitutes the main factor responsible for the
      prevalence of resistance in this environment. Among 380 isolates, 56 multidrug
      resistant E. coli with a similar resistant phenotype were selected for more
      detailed investigations including a genomic similarity analysis and the detection
      of mobile elements. Isolates carried blaTEM-1, aadA1, strA/B, tetA, tetB, tetC,
      dfrA1, dfrA5, dfrA7, dfrA12, sul1, sul2, sul3, and qnrS resistance genes, with
      the common co-occurrence of genes encoding the same resistance phenotype. A pulse
      field gel electrophoresis analysis of the genomic similarity of multidrug
      resistant E. coli showed <=65% similarity of most of the tested strains and did
      not reveal a dominant clone responsible for the prevalence of resistance. Class 1
      and 2 integrons and transposons 7 and 21 were detected among mobile elements;
      however, some were truncated. Plasmids were represented by 11 different
      incompatibility groups (K, FIB, I1, FIIA, FIC, FIA, Y, P, HI1, B/O, and T).
      Genetic resistance traits were unevenly spread in the clonal groups and suggested
      the major rearrangement of genetic material by horizontal gene transfer. The
      present results revealed that in commensal E. coli from pigs in a homogeneous
      farm environment, there was no dominant clone responsible for the spread of
      resistance and persistence in the population.

PMID- 30210142
TI  - Cardiovascular Risks of Ketogenic Diet for Glut-1 Deficiency.
AB  - Investigators from Children's Hospitals of Aschaffenburg-Alzenau, Germany, and
      Essen University, Germany reported on long-term cardiovascular risks of ketogenic
      diet (KD) treatment for Glut1 Deficiency syndrome (GLUT1-DS).

PMID- 30210143
TI  - Maximizing Benefits With the Medication Use Evaluation Process.

PMID- 30210141
TI  - Melatonin Upregulates Nuclear Factor Erythroid-2 Related Factor 2 (Nrf2) and
      Mediates Mitophagy to Protect Against Early Brain Injury After Subarachnoid
      Hemorrhage.
AB  - BACKGROUND The aim of this study was to investigate whether melatonin is involved
      in brain injury following subarachnoid hemorrhage (SAH). MATERIAL AND METHODS An
      SAH model was established and TUNEL assays were utilized to detect the effect of
      melatonin on cell apoptosis. Western blot analysis was used to detect the effect
      of melatonin on expression of autophagic markers and apoptotic factors. Real-time
      PCR, Western blot analysis, and luciferase assay were performed to study the
      effect of melatonin on nuclear factor erythroid-2 related factor 2 (NRF2)
      expression. RESULTS The SAH group displayed a lower neurological score and a
      higher brain water content, while melatonin treatment increased the neurological
      score and decreased the brain water content. The administration of melatonin also
      inhibited the apoptosis of neurons in the brain. In addition, higher Beclin-1
      expression and higher conversion ratio from LC3- II to LC3-I were observed in the
      SAH group. The activation of Beclin-1 and the conversion from LC3-II to LC3-I was
      further enhanced by melatonin treatment. Furthermore, in the SAH group, the level
      of Bcl-2 was decreased while the level of Bax and cleaved caspase-3 were
      increased. However, following melatonin treatment in the SAH group, the level of
      Bcl-2 was increased while the levels of Bax and cleaved caspase-3 were decreased.
      CONCLUSIONS Our study indicated that, by increasing the expression of NRF2, the
      mitophagy induced by melatonin provided protection against brain injury post-SAH.

PMID- 30210144
TI  - Coagulation Factor Xa (Recombinant), Inactivated-zhzo (Andexanet Alfa).
AB  - Each month, subscribers to The Formulary Monograph Service receive 5 well
      documented monographs on drugs that are newly released or are in late phase 3
      trials. The monographs are targeted to Pharmacy & Therapeutics Committees.
      Subscribers also receive monthly 1-page summary monographs on agents that are
      useful for agendas and pharmacy/nursing in-services. A comprehensive target drug
      utilization evaluation/medication use evaluation (DUE/MUE) is also provided each
      month. With a subscription, the monographs are available online to subscribers.
      Monographs can be customized to meet the needs of a facility. Through the
      cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in
      this column. For more information about The Formulary Monograph Service, contact
      Wolters Kluwer customer service at 866-397-3433.

PMID- 30210145
TI  - ISMP Adverse Drug Reactions: Adalimumab-Induced Aseptic Meningitis Pill Desiccant
      -Induced Acute Hypoxic Respiratory Failure Rivastigmine Patch -Induced Angioedema
      Acute Liver Failure Due to Etodolac Severe Cognitive Impairment Due to High Free
      Valproic Acid Levels.
AB  - The purpose of this feature is to heighten awareness of specific adverse drug
      reactions (ADRs), discuss methods of revention, and promote reporting of ADRs to
      the US Food and Drug Administration's (FDA) MedWatch program (800-betaDA-1088).
      If you have reported an interesting, preventable ADR to MedWatch, please consider
      sharing the account with ur readers. E-mail
      Dr.Mancanomichael.mancano@temple.edu). Your report will be published anonymously
      unless otherwise requested. This feature is provided by the Institute for Safe
      Medication Practices (ISMP) in cooperation with the FDA's MedWatch program and
      Temple University School of Pharmacy. ISMP is an FDA MedWatch partner.

PMID- 30210146
TI  - Pharmacy Operationalization of the Intralesional Oncolytic Immunotherapy
      Talimogene Laherparepvec.
AB  - Objective: Oncolytic immunotherapy involves the use of viruses to target and
      destroy cancer cells and to induce immune responses for an enhanced antitumor
      effect. Talimogene laherparepvec, a genetically modified herpes simplex virus
      type 1 (HSV-1) that selectively replicates in tumors to induce lytic cell death,
      tumor antigen release, and the local production of granulocyte-macrophage colony
      stimulating factor (GM-CSF), has been approved for the treatment of a defined
      population of patients with metastatic melanoma. Talimogene laherparepvec is
      administered as a series of intralesional injections, and specific procedures are
      implemented to minimize the risk of viral exposure. Because talimogene
      laherparepvec represents a novel therapeutic modality, its preparation,
      administration, and handling requirements differ from current therapies;
      pharmacists have an important role in developing new procedures to incorporate it
      into clinical practice. Methods: In this review, pharmacists with experience
      dispensing talimogene laherparepvec, in the clinical trial setting and/or as a
      commercially available product at US academic institutions, synthesized their
      personal experiences through group discussions to provide insights on the
      ordering, receipt, storage, preparation, administration, and handling of
      talimogene laherparepvec. Results: Suggestions for patient education and
      practical guidance to assist hospital pharmacists and decision makers with
      implementing talimogene laherparepvec at their institutions are provided.
      Conclusion: These insights may further inform the development of policies or
      procedures to incorporate talimogene laherparepvec into clinical settings and
      improve patient outcomes.

PMID- 30210147
TI  - Change in Management of Status Epilepticus With the Addition of Neurointensivist
      Led Neurocritical Care Team at a Rural Academic Medical Center.
AB  - Learning Objective: Status epilepticus (SE) is continuous clinical and/or
      electrographic seizures lasting 5 minutes or more without recovery and carries a
      high mortality. Medication management varies by institution, as well as
      administration, combination of antiepileptic drugs (AEDs), and dosing. Methods:
      Single-center retrospective review of medication management of SE patients
      admitted to West Virginia University Hospital before and after neurointensivist
      implemented guidelines. Patients admitted between January 2012 and June 2014 were
      grouped in the prior to neurointensivist group (pre-NI) and patients admitted
      between July 2014 and June 2016 were grouped in the postneurointensivist group
      (post-NI). Baseline demographics, hospital, intensive care unit (ICU), and
      ventilator length of stay were recorded. Medications reviewed included number of
      AEDs and maximum dose of lorazepam, phenytoin, levetiracetam, and lacosamide.
      Outcomes included number of continuous infusions of either midazolam or propofol
      at seizure suppression doses as well as pentobarbital, phenobarbital, or
      ketamine, and need for vasopressor use. Results: Of the 74 patients included, the
      pre-NI group (n = 40) utilized more AEDs (6 vs 4) compared with the post-NI group
      (n = 34). The pre-NI group had less midazolam continuous infusions meeting
      seizure suppression doses (8 vs 9), but higher average doses (49 vs 27 mg/h)
      compared with the post-NI group. More patients in the pre-NI group were on
      propofol seizure suppression doses (15 vs 10) and phenobarbital continuous
      infusions (11 vs 2) than the post-NI group. Patients had less vasopressor use in
      the post-NI group than the pre-NI group (11 vs 23). Frequency and dosing of
      lorazepam, phenytoin, levetiracetam, and lacosamide were similar between the 2
      groups. Ventilator use, hospital, and ICU length of stay were also similar
      between groups. Discussion: Implementation of a neurointensivist and medication
      guidelines resulted in fewer AEDs and less vasopressor use in the management of
      SE. Midazolam use was slightly higher in the post-NI group but at lower doses
      overall.

PMID- 30210148
TI  - Newly Initiated In-Hospital Antipsychotics Continued at Discharge in Non
      psychiatric Patients.
AB  - Objectives: Antipsychotics are commonly initiated in the hospital for agitation
      and delirium and may be inappropriately continued upon floor transfer and at
      discharge. We sought to evaluate the magnitude of this issue within our health
      care system. Methods: We conducted a multicenter, retrospective cohort study
      within a 22-hospital health care system to evaluate the proportion of patients
      without identifiable psychiatric illness who received newly initiated inpatient
      antipsychotics and were then continued on an antipsychotic at hospital discharge.
      Results: Of 23 049 patients who received at least 1 in-hospital dose of
      haloperidol, olanzapine, quetiapine, risperidone, or ziprasidone, 8297 patients
      were included in the final analysis after applying exclusion for identifiable
      psychiatric illness or previous antipsychotic use. Ultimately, 334 patients (4%)
      were discharged with a new antipsychotic prescription. Patients receiving
      antipsychotics at discharge were more likely as an inpatient to receive
      quetiapine (77.2% vs 35.9%; odds ratio [OR]: 6.1, 95% confidence interval [CI]:
      4.7-8.0; P < .001) and less likely to receive haloperidol (15% vs 47%; OR: 0.2,
      95% CI: 0.14-0.27; P < .001) or olanzapine (16.2% vs 20.9%; OR: 0.73, 95% CI:
      0.53-0.98; P < .04). Conclusions: Antipsychotics may be inappropriately continued
      in non-psychiatric patients at hospital discharge. Strategies to limit
      potentially unnecessary antipsychotics upon discharge should be evaluated.

PMID- 30210149
TI  - Perioperative Intravenous Acetaminophen in Pediatric Tonsillectomies.
AB  - Purpose: This study investigated the effect of perioperative intravenous (IV)
      acetaminophen on opioid requirements in pediatric patients undergoing
      tonsillectomy at a single center. Methods: This retrospective chart review
      included patients who were less than 18 years old and underwent an outpatient
      tonsillectomy procedure. Patients who received non-Food and Drug Administration
      (FDA)-approved dosing of IV acetaminophen, without documented weights, and on
      chronic pain medications at the time of the procedure were excluded. The primary
      outcome was opioid requirements postoperatively prior to discharge measured as
      morphine equivalents per kilogram. Descriptive statistics were used to compare
      differences between groups. A multivariate analysis was performed, accounting for
      differences between groups in baseline and procedural characteristics. Results:
      In total, 157 patients were included in this study, of whom 55 had received IV
      acetaminophen and 102 had not. The average IV acetaminophen dose for was 14.5
      mg/kg for patients weighing less than 50 kg (n = 22); the remaining patients
      received the maximum 1 g dose. Patients who received IV acetaminophen were less
      likely to be administered postoperative opiates as compared with those did not
      (45.5% vs 63.7%, odds ratio = 0.48, P = .036). There was a trend toward a
      decrease in total amount of opiates administered with IV acetaminophen (0 vs
      0.033 ug/kg, P = .61). After adjusting for age and documented pain assessment, IV
      acetaminophen administration remained a significant factor for postoperative
      opiate administration. Conclusions: Perioperative administration of IV
      acetaminophen was associated with less frequent administration of symptom
      directed opiates in pediatric tonsillectomies. This finding indicates that the
      agent may have an opioid-sparing effect in this patient population.

PMID- 30210150
TI  - A Financial Evaluation of the Centralized Repackaging of Intracameral
      Moxifloxacin for Cataract Surgery and Its Impact on Cost Reduction.
AB  - Background: Extensive evidence-based literature supports the use of intracameral
      (IC) moxifloxacin for the prevention of postoperative endophthalmitis after
      cataract surgery. The Aurora Pharmacy Packaging Center (APPC) has developed a
      process for centrally preparing IC moxifloxacin. Purpose: The aim of this study
      was to evaluate the centralized preparation of IC moxifloxacin production for
      quality assurance and to quantify a potential reduction in costs. Methods: The
      APPC's compounding procedure of IC moxifloxacin was evaluated using United States
      Pharmacopeia (USP) Convention 797 standard and compared with practices described
      in evidence-based literature. Patients who received IC moxifloxacin
      intraoperatively from one of 3 ophthalmologists during cataract surgery performed
      between February 15, 2016, and August 15, 2016, were identified using electronic
      health records. Cost savings were calculated by reviewing costs associated with
      drug supplies used by the APPC. Results: The APPC process for the centralized
      preparation of IC moxifloxacin was deemed compliant with USP 797's sterile
      compounding standards. USP 797 validation criteria included proper sterile
      technique, equipment, room sterility and pressure, beyond use dating, and
      storage. Implementation of the centralized production of moxifloxacin reduced the
      direct product cost per surgery from $140 to $20 (a cost savings of $120 per
      surgery). There were 459 cataract surgeries analyzed during the study period,
      resulting in a savings of $55 080 over 6 months. Conclusion: The APPC's
      centralized compounding procedure was found to be compliant with pharmacy
      compounding standards and to yield significant cost savings.

PMID- 30210152
TI  - Dosing of Enoxaparin in Morbidly Obese Patients: A Retrospective Cohort.
AB  - Purpose: The purpose of this study was to evaluate odds of major bleeding,
      thrombosis, and ischemic stroke between different enoxaparin dosage strategies in
      patients weighing >=120 kg. Methods: Patients weighing >=120 kg who received
      therapeutic anticoagulation with enoxaparin for more than 24 hours were selected
      for retrospective review. Patients without a baseline weight, serum creatinine, a
      history of heparin-induced thrombocytopenia, or currently pregnant patients were
      excluded from the study. Patients with a creatinine clearance (CrCL) <30 mL/min
      were analyzed separately. The incidence of major bleeding was compared between
      patients receiving <90% and those receiving >=90% of the Food and Drug
      Administration (FDA)-approved dose of enoxaparin, as well as between patients
      weighing >=150 kg and those weighing <150 kg. Secondary outcomes included
      incidence of venous thromboembolism (VTE) and ischemic stroke. Results: A total
      of 462 patients were included in the primary analysis and 25 patients in the
      subgroup analysis. No difference in major bleeding was observed between different
      dosage regimens (P = .12) or weight groups (P = .36). No difference was observed
      in rates of VTE or ischemic stroke between different dosage regimens (P = .52 and
      P = .60, respectively) or weight groups (P = .39 and P = .48, respectively).
      Similar results were observed in the low-CrCL analysis. Results were not altered
      when patients were propensity matched on baseline characteristics. Conclusion:
      Reducing the dose of enoxaparin did not reduce the odds of major bleeding or
      increase the odds of ischemic stroke or VTE.

PMID- 30210151
TI  - Comparison of Plasma-Lyte A and Sodium Chloride 0.9% for Fluid Resuscitation of
      Patients With Diabetic Ketoacidosis.
AB  - Purpose: The aim of this study was to compare Plasma-Lyte A (PL) and sodium
      chloride 0.9% (NS) in regard to time to resolution of diabetic ketoacidosis (DKA)
      when one fluid was used predominantly over the other for resuscitation. Methods:
      We performed a retrospective analysis of the records of patients treated for DKA
      at a large, academic medical center between July 1, 2013, and July 1, 2015.
      Patients were placed into the PL or NS group based on the predominant fluid they
      received during fluid resuscitation. Serum biochemistry variables were
      categorized as follows: initial, 2 to 4 hours, 4 to 6 hours, 6 to 12 hours, and
      12 to 24 hours. The primary outcome was mean time to resolution of DKA. Results:
      Eighty-four patients were included in the study. The primary outcome of mean time
      to resolution of DKA was similar between the PL (19.74 hours) and NS (18.05
      hours) groups (P = .5080). Patients treated with PL had a significantly greater
      rise in pH within the 4- to 6-hour and 6- to 12-hour periods. The chloride level
      was significantly higher and the anion gap was significantly lower for the NS
      group in the 6- to 12-hour period. Conclusion: These data suggest that the use of
      PL for fluid resuscitation in DKA may confer certain advantages over NS.

PMID- 30210153
TI  - Improved Arrangement and Capacity for Medication Transactions: A Pilot Study to
      Determine the Impact of New Technology on Medication Storage and Accessibility.
AB  - Purpose: A new-generation automated dispensing cabinet (ADC) deployment is
      described. Methods: A single-center retrospective-prospective pilot product
      performance study was conducted, and prospective nurse satisfaction survey and
      pharmacy technician product performance feedback survey were performed to
      determine the impact of new technology on medication storage and accessibility.
      The study measured efficiency of the 9:00 am medication pull for nursing users,
      assessment of nursing perceptions of medication administration pre- and
      postinstallation of the cabinetry, pharmacy technician perceptions of working
      with the cabinetry, and assessment of the efficiency of the pharmacy technician
      restock process. Results: In total, 2981 total nursing medication retrieval
      processes for the 9 am standard medication administration time (SMAT) time were
      analyzed: 1321 in the preoptimization phase and 1660 in the postoptimization
      phase. Analysis of the mean time per transaction confirmed a significant
      improvement from 10.5 to 10.3 seconds per transaction (P = .026) in the
      postoptimization configuration. The modified assessment of nursing satisfaction
      survey demonstrated increased satisfaction with many aspects of the new
      generation cabinetry. Pharmacy technician survey data highlighted beneficial
      aspects of the device, while restock data showed an increase in the time spent
      restocking the cabinet from 11.5 seconds in the preoptimization phase compared
      with 21.3 seconds in the postoptimization phase (P < .0001). Conclusion: ADC
      installation and inventory optimization had a statistically significant
      improvement in the mean time per nursing transaction. Nursing and pharmacy
      technician surveys demonstrated a trend of enhanced satisfaction with the
      platform.

PMID- 30210154
TI  - Two Years of Retrospective Study on the Incidence of Tuberculosis in Dir Lower
      Valley, Khyber Pakhtunkhwa, Pakistan.
AB  - Background: Pakistan has high tuberculosis (TB) burden with alarming mortality
      and morbidity, and its rate increases day by day, especially in remote areas
      where access of quality health is not available. Objective: The objective of the
      study was to determine the incidence rate of pulmonary TB in the Dir valley among
      the suspected patients according to age-, gender-, and location-wise prevalence
      of the disease. Methods: A retrospective descriptive study was designed from
      January 2015 to December 2016. All the 556 people registered are suspected
      patients of pulmonary tuberculosis sputum smear (PTB-SS) positive, whereas the
      remaining cases were diagnosed with extra-pulmonary TB and hence excluded from
      the study. Results: The ratio of PTB-SS-positive cases was higher in females
      (50.5%, n = 281) compared with males (49.5%, n = 275). Furthermore, in the age
      group 1 to 20 years, the percentage of PTB-SS-positive cases was 28.1% (n = 156),
      in 21 to 40 years 40.3% (n = 224), in 41 to 60 years 18.7% (n = 104), in 61 to 80
      years 11.2% (n = 62), and at age group >81 years, it was 1.8% (n = 10). No
      difference was found in the years 2015 and 2016 regarding PTB-SS-positive cases
      registration. Age and health care facilities (P < .000) and treatment outcome (P
      < .000) have a strong relationship. No significant relation was found with other
      demographics variables (P > 0.05). Conclusion: It was concluded from our finding
      that TB was considerably increased in the general population of District Dir
      (Lower), and proper supervision, diagnosis, treatment, and awareness of rapid
      prophylactic measures are needed to eradicate the issue.

PMID- 30210155
TI  - Antifungal Resistance in Dermatology.
AB  - Cutaneous fungal infections affect more than one-fourth of world's population.
      The pathogenesis and severity of fungal infection depend on various immunological
      and nonimmunological factors. The rampant use of antifungal therapy in
      immunocompromised individuals marked the onset of antifungal drug resistance.
      Fungal resistance can be microbiological or clinical. Microbiological resistance
      depends on various fungal factors which have established due to genetic
      alteration in the fungi. Clinical resistance is due to host- or drug-related
      factors. All these factors may cause fungal resistance individually or in tandem.
      In addition to standardized susceptibility testing and appropriate drug dosing,
      one of the ways to avoid resistance is the use of combinational antifungal
      therapy. Combination therapy also offers advantages in increased synergistic
      action with enhanced spectrum activity. Newer insights into mechanisms of drug
      resistance will help in the development of appropriate antifungal therapy.

PMID- 30210157
TI  - Topical Steroid Damaged/Dependent Face (TSDF): A Study from a Tertiary Care
      Hospital in Eastern India.
AB  - Background: Awareness against abuse of topical corticosteroids (TC), especially
      over the face, has been going on for last 5 years in India. In spite of that we
      are getting lots of cases in our hospitals. Aims: The aims of this study were to
      ascertain the demographics, magnitude and clinical features of TC misuse on the
      face among the dermatology outpatient department (OPD) attendees and to analyze
      its causes. Methods: This study was conducted in a tertiary care medical center
      of eastern India. Patients with relevant facial dermatoses were asked about their
      current use of topical formulations and confirmed to be TSDF were included in the
      study. Results: A total of 748 patients with facial dermatoses were screened, of
      which 271 (36.22%) were using TC. Of them mostly young adults between 20 and 29
      years (37.10%) were using TC. Average duration between starting of use of
      medication and the onset of symptoms was 5 months. Ninety-eight (36.16%) patients
      were using topical corticosteroid for the treatment of acne and 74 (27.30%) were
      using as depigmenting cream. About 108 (39.85%) patients bought medicine over the
      counter being recommended by pharmacist/shop owner. Rosacea like features with
      photosensitivity was the most common adverse effect found in 79 (29.15%) patients
      whereas comedonal acne/acne exacerbation were found in 68 (25.09%) patients. Most
      of them (227, 83.76%) were unaware about the side effects of steroids.
      Conclusions: TC misuse in patients with facial dermatoses is still quite common
      even after efforts to grow the awareness among population.

PMID- 30210156
TI  - Estimation of Zinc and Iron Levels in the Serum and Hair of Women with
      Androgenetic Alopecia: Case-control Study.
AB  - Background: Although female androgenetic alopecia (FAGA) occurs in genetically
      susceptible women, some trace elements may play an important role. Aim of the
      Study: This study aimed to evaluate serum and hair zinc and iron levels in
      patients with FAGA and to compare the findings with normal controls. Patients and
      Methods: A case-control study that was conducted at Dermatology Clinic in Basra
      General Hospital, Basra, Iraq. The participants were divided into two groups: The
      first group consisted of 27 women with FAGA and the second was age-matched 28
      healthy women control group. The serum and hair zinc and iron assays were done
      for all participants. Results: Both hair and serum zinc levels in FAGA group were
      significantly lower than that in the control (103.4+/-25.5 ppm vs. 143.5+/-33.1
      ppm for hair and 65.6+/-14.2 MUg/dl vs. 128.4+/-41.4 MUg/dl for serum). Hair iron
      level in FAGA was significantly lower than in control (17.9+/-3.8 ppm vs. 26.9+/
      7.4 ppm, P>0.05). Serum iron level in FAGA group was lower than in the control,
      but it was not significant statistically (88.9+/-22.3 MUg/dl vs. 100.9+/-18.9
      MUg/dl). Except for the hair iron, there was no significant correlation between
      zinc and iron concentrations in hair and serum with severity of alopecia.
      Conclusions: Zinc and iron levels in serum and hair were lower in FAGA compared
      to that of normal individuals indicating that trace elements might play an
      important role in the etiopathogenesis of FAGA.

PMID- 30210158
TI  - Comparison of Efficacy of Doxycycline and Isotretinoin on Cutaneous Human Beta
      Defensin-1 and -2 Levels in Acne Vulgaris.
AB  - Background: Recent studies have shown that human beta-defensin-1 (hBD-1) and
      (human beta-defensin-2 hBD-2), which are antimicrobial peptides produced by the
      skin, play a role in the pathogenesis of acne vulgaris (AV). Objective: The aim
      of this study was to determine the role of antimicrobial peptides in the
      pathogenesis of AV and enlighten the effects of doxycycline and isotretinoin in
      the expression of these defensins in AV. Materials and Methods: A total of 44
      patients (22 patients in each group) with Grade 6 and 8 AV who were indicated
      doxycycline or isotretinoin for their treatment, and 20 healthy volunteers were
      included in this study. Pretreatment cutaneous samples were obtained from
      pustular lesions and uninvolved skin of AV patients and were repeated after the
      treatment. Only one biopsy was obtained from controls. Results: Cutaneous levels
      of hBD-1 and hBD-2 were significantly increased in AV patients when compared with
      healthy controls (P<0.05). Doxycycline therapy achieved a decrease in hBD-1
      levels (P<0.05), whereas isotretinoin therapy achieved a reduction in hBD-2
      levels when compared with pretreatment levels (P<0.05). Posttreatment hBD-1 and
      hBD-2 levels were not different between doxycycline and isotretinoin groups
      (P>0.05). Conclusion: In the light of these results, it was reasonable to assume
      the role of hBD-1 and hBD-2 in the pathogenesis of AV. Our results showing a
      significant reduction in hBD-1 staining with doxycycline treatment and in hBD-2
      with isotretinoin suggested that some part of their anti-acne effect worked
      through these mechanisms.

PMID- 30210159
TI  - Pathogenic Yeasts Recovered From Acne Vulgaris: Molecular Characterization and
      Antifungal Susceptibility Pattern.
AB  - Context: Acne vulgaris is a disorder showing persistent inflammation in the
      pilosebaceous follicles. It is one of the most prevalent dermatoses that millions
      of people suffer from globally. Aim: The aim of this study was to identify
      Candida species from patients with acne and to determine their drugs
      susceptibility. Subjects and Methods: A total of 70 cutaneous samples from acne
      vulgaris patients suspected to have Candida infections were collected.
      Macroscopic and microscopic morphology were recorded followed by polymerase chain
      reaction-sequencing of ITS regions, using universal primers. In vitro antifungal
      susceptibility was performed using Clinical and Laboratory Standards Institute
      method. Results: Overall, 11 Candida species including Candida parapsilosis 8
      (72.73%), Candida krusei 1 (12.5%), Candida lusitaniae 1 (12.5%), Candida kefyr 1
      (12.5%), and a Trichosporon asahi out of the collected clinical materials were
      isolated and identified. C. parapsilosis isolates susceptibility to diverse
      concentrations of the antifungal agents to isolate Cp1 study indicated that the
      isolated Cp8 and Cp5 with minimal inhibitory concentration (MIC) 50 = 32, 0.5,
      0.25 and MIC 90 of <64, <1, <0.5 MUg/ml fluconazole, itraconazole, and
      ketoconazole were resistant, respectively. Some of the isolates having relative
      strength, almost all other species of C. parapsilosis isolates were susceptible
      to these drugs. Conclusion: C. parapsilosis was the most prevalent Candida
      species in acne vulgaris samples which had higher in vitro susceptibility for
      antifungals.

PMID- 30210161
TI  - Impact on Quality of Life in Vitiligo Patients Treated with Narrowband
      Ultraviolet B Phototherapy.
AB  - Context: Vitiligo is a psychosocial problem which significantly affects quality
      of life in Indian scenario. Aims: The purpose of this study was to compare the
      changes in quality of life in patients of vitiligo before and after treatment
      with narrowband ultraviolet B (NBUVB) phototherapy. Subjects and Methods: A total
      of 54 patients had completed the study. The age ranged between 16 and 70 years
      with a mean age of 26.77+/-14.2 years. The initial dose of NBUVB was 300 mJ/cm2
      in adults and 150 mJ/cm2 in children twice weekly with 20% dose increment on
      subsequent visits. It was given for a maximum period of 6 months and was followed
      up for another 6 months to determine stability of repigmentation. Results: The
      average number of exposure given to the patients was 45.63+/-12.74 while the mean
      irradiation cumulative dose was 39.8 J/cm2. Mean Dermatology Life Quality Index
      (DLQI) of the vitiligo patients was 8.64+/-4.32 while those patients with
      acrofacial vitiligo had a mean DLQI of 11.78+/-5.61. After treatment with NBUVB,
      mean DLQI of all vitiligo patients was significantly reduced to 5.86+/-2.15
      (P<0.01). Conclusions: This study showed that phototherapy had a positive
      therapeutic outcome in vitiligo, especially in younger patients. Even a small,
      depigmented lesion in a child could be psychosocially devastating.

PMID- 30210162
TI  - A Comparative Study of Combined Dermaroller and Platelet-Rich Plasma Versus
      Dermaroller Alone in Acne Scars and Assessment of Quality of Life Before and
      After Treatment.
AB  - Background: Scarring due to acne is a frequently encountered problem in
      dermatological outpatient department. Microneedling has been a well-accepted
      modality for the treatment of atrophic acne scars. Platelet-rich plasma (PRP) is
      a newer option to investigate. Aims: The aims of this study were (1) to compare
      the efficacy of combined dermaroller and PRP therapy with dermaroller alone in
      facial acne scars and (2) to assess the psychosocial impact due to acne scars and
      its treatment. Methods: A total of 55 patients were included in the study and
      randomly divided into two groups, Group A: 28 and Group B: 27. Proper counseling
      was done, and detailed clinical findings were recorded. Patients in Group A were
      treated with dermaroller alone while Group B patients underwent treatment with a
      combination of dermaroller and intradermal PRP injections. A total of three
      sitting were done at monthly interval. Final response was assessed at 1 month
      after the last sitting. Criteria of evaluation included Goodman and Baron's
      quantitative scale, visual analog score, and dermatology life quality index
      scores. Side effects were noted. Results were analyzed using Chi-square test and
      t-test. Results: Significant percentage improvement was noted in both the groups.
      However, Group B treated with both modalities had better results when compared
      with that in the Group A. Conclusion: A combination approach using dermaroller
      and PRP was a safe and better option than using dermaroller alone in atrophic
      acne scars for clinical improvement as well as for improvement in dermatology
      life quality index score.

PMID- 30210163
TI  - Idiopathic Eruptive Macular Pigmentation - Uncommon Presentation of an Uncommon
      Condition.
AB  - Idiopathic eruptive macular pigmentation (IEMP) is an asymptomatic condition with
      dark brown, nonconfluent lesions chiefly occurring in children and adolescents.
      The usual sites involved are face, trunk, extremities, and the lesions resolve
      over few months to years. We report an unusual presentation of this uncommon
      condition. A 22-year-old male presented with multiple dark-colored asymptomatic
      lesions on the scalp and forehead for the past 3 years. There was no history of
      preceding symptoms, drug, or applications, past or family history of such
      lesions. Examination revealed multiple hyperpigmented macules and barely elevated
      nonscaly plaques with a velvety feel akin to acanthosis nigricans (AN).
      Dermoscopy was similar to AN. Blood sugar, thyroid, and lipid profiles were
      normal. Histology showed "pigmented papillomatosis" concluding the final
      diagnosis of IEMP. Confluence of lesions is a rarely described phenomenon, with
      the scalp being a hitherto unreported site. The velvety feel of lesions, the
      dermoscopic, and histopathological findings further substantiate the hypothesis
      of this entity being an eruptive variant of AN.

PMID- 30210160
TI  - Sensitization to Fungi in Atopic Dermatitis Patients 14 Year and Older -
      Association with Other Atopic Diseases and Parameters.
AB  - Background: Fungi as a source of allergen are still largely neglected in basic
      research as well as in clinical practice. This study aimed to highlight the
      impact of fungal allergens in a group of patients suffering from atopic
      dermatitis (AD). Aims and Objectives: The evaluation of the sensitization to
      fungi in AD patients aged 14 year and older and the evaluation of the relation of
      fungal sensitization to the occurrence of other atopic diseases and parameters.
      Materials and Methods: All patients satisfying inclusion criteria attending our
      hospital between 2008 and 2017 were included in the study. The complete
      dermatological and allergological examinations were performed in all included
      patients including examination of specific immunoglobulin E, skin prick test to
      mixture of fungi and inhalant allergens, evaluation of asthma bronchiale,
      rhinitis, onset of AD, family history about atopy, duration of eczematous
      lesions, severity of AD. Pairs of these categories were entered in the
      contingency tables and the Chi-square test for relationship of these variables
      was performed with the level of significance set below 5%. Results: Three hundred
      and thirty-one patients were included in the study; the average age was 26.8
      years. The sensitization to fungi was recorded in 100 patients (30%). In these
      patients, the occurrence of asthma bronchiale, rhinitis, family history about
      atopy, sensitization to grass and trees was significantly higher than in patients
      without sensitization to fungi. We did not find any significant relation between
      the sensitization to fungi and the severity of AD, no relation was also found
      between the sensitization to fungi and sensitization to mites, animal dander,
      bird feather, and dust. Conclusion: The occurrence of asthma bronchiale,
      rhinitis, family history about atopy, sensitization to grass and trees was
      significantly higher in AD patients with sensitization to fungi. No relation was
      found between the severity of AD and the sensitization to fungi.

PMID- 30210164
TI  - A Distinct Clinicopathological Presentation of Cutaneous Dermatophytosis
      Mimicking Autoimmune Blistering Disorder.
AB  - Infectious diseases can clinically present as vesiculobullous disorders. Direct
      immunofluorescence (DIF) study of skin biopsy helps distinguish true autoimmune
      blistering disorders from other conditions. In many situations, even DIF findings
      in infections disorders imitate autoimmune process. Here, we describe a case of
      29-year-old female with extensive dermatophytosis having presentation mimicking
      bullous pemphigoid both clinically and histopathologically including DIF
      findings.

PMID- 30210165
TI  - Bullous Pemphigoid Induced by Metamizole in a Pediatric Patient.
AB  - Bullous pemphigoid (BP) is an autoimmune bullous disease commonly seen in adult
      population but rarely encountered in the pediatric population. Although the exact
      etiology of BP remains unclear, various vaccines, infectious agents, and drug use
      have been blamed in the etiology of BP. Here, we present a 14-year-old patient
      who developed BP after using metamizole and whose diagnosis was clinically and
      histopathologically confirmed.

PMID- 30210166
TI  - Overlap Syndrome with Rowell's Syndrome, Antiphospholipid Syndrome, Primary
      Sterility, and Sensorineural Hearing Loss: A Case Report, Brief Review, and
      Analysis of Cases of Rowell's Syndrome Reported from India and Abroad.
AB  - Rowell's syndrome (RS) is recognized since 1963 as a presentation of lupus
      erythematosus (LE) with erythema multiforme-like lesions and characteristic
      immunological changes. Antiphospholipid syndrome (APS) encompasses antibodies to
      phospholipids/phospholipid-binding cofactor proteins and/or circulating lupus
      anticoagulant with clinical manifestations of thrombosis such as recurrent
      spontaneous abortions, etc. A 32-year-old female with primary infertility since
      marriage (7 years) and sequential appearance, for the past 6 months, of various
      lupus-specific cutaneous lesions, "targetoid" lesions on palms, musculoskeletal,
      ocular and auditory (sensorineural hearing loss [SNHL]) complaints with positive
      serological profile for SMD-1, SS-A/Ro, SS-B/La, U1-snRNP, Ku, antiphospholipid
      and anticardiolipin antibodies, and histopathologically confirmed LE is presented
      as a case of concurrent overlap syndrome, RS and APS, primary infertility, and
      SNHL. A brief review of RS including analysis of data of cases reported from
      India hereto vis-a-vis that of cases worldwide up to 2012 has also been done.

PMID- 30210168
TI  - A case of Bullous Pemphigoid Associated with Lichen Sclerosus et Atrophicus.

PMID- 30210167
TI  - Metastatic Dermatosis in Breast Carcinoma on Adjuvant Trastuzumab: Is Skin a
      Sanctuary Site in Human Epidermal Growth Factor Receptor-2-Amplified Disease?
AB  - Cutaneous metastasis (CM) from internal malignancies is commonly seen. Sometimes,
      skin metastases can be the first sign of advanced cancer or an indicator of
      cancer recurrence. Cases of breast cancer with cutaneous progression after or
      during trastuzumab therapy have been described in the past, frequently associated
      with systemic disease progression. However, CM during adjuvant trastuzumab
      therapy is very rare. It has been hypothesized that cancer cells located in the
      skin survive and take proliferative advantage by virtue of an immune-tolerance
      mechanism that hampers trastuzumab-mediated antibody-dependent cell-mediated
      cytotoxicity. We describe a case of human epidermal growth factor receptor-2
      overexpressing breast cancer presenting with diffuse CM during adjuvant
      trastuzumab therapy.

PMID- 30210169
TI  - Sweet's Syndrome Associated with Talaromyces marneffei and Mycobacterium
      abscessus Infection Due to Anti-interferon-gamma Autoantibodies.

PMID- 30210170
TI  - Familiar Manifestations of Unfamiliar Selenium Toxicity.

PMID- 30210171
TI  - Cyclosporine in Generalized Bullous-Fixed Drug Eruption.

PMID- 30210172
TI  - Kaposi's Varicelliform Eruption in a Patient with Darier's Disease.

PMID- 30210173
TI  - Use of an Anal Retractor Device for Excision in Patients with Perianal
      Extramammary Paget's Disease.

PMID- 30210174
TI  - Bibliometric Evaluation of Global Productivity of Teledermatology Publications
      between 1975 and 2017 with a 3-Year Update.

PMID- 30210176
TI  - The Usefulness of Dermoscopy in Extraocular Sebaceous Carcinoma.

PMID- 30210175
TI  - Dermatofibrosarcoma Protuberans Secondary to a Decorative Tattoo: An
      Isotattootopic Response?

PMID- 30210177
TI  - Three Sequential Lymphomatous Tumors in a Patient.

PMID- 30210178
TI  - Accessible Diagnostic Methods to Differentiate between Epidermolysis Bullosa
      Acquisita and Other Subepidermal Autoimmune Bullous Diseases.

PMID- 30210179
TI  - Effective Word-Problem Instruction: Using Schemas to Facilitate Mathematical
      Reasoning.

PMID- 30210180
TI  - Association of providing/receiving support on the mortality of older adults with
      different living arrangements in Taiwan: a longitudinal study on ageing.
AB  - This longitudinal study evaluated the direct effects of providing/receiving
      family support on mortality in older adults with different living arrangements in
      Taiwan. All data analysed were obtained from the Taiwan Longitudinal Study on
      Aging, 1996-2007, of residents aged ?67 years (1,492 men and 1,177 women) and
      Taiwan's National Death Register. Living arrangements were divided into living
      alone, living only with spouse, living with family and living with others.
      Support was mainly defined as family support divided into two categories:
      providing and receiving. The effect of providing/receiving family support on the
      mortality of older adults was evaluated using Cox regression analysed by living
      arrangement. Participants living with their families had lower educational levels
      (illiterate or elementary school) and more disability in both activities of daily
      living and instrumental activities of daily living. However, they provided more
      family support than those in other living arrangements. After adjusting for
      several potentially confounding variables, including background characteristics,
      economic status and various health status measures, results showed that older
      adults living with their families and providing support had an 11 per cent lower
      mortality rate (Hazard ratio = 0.89; 95 per cent confidence interval = 0.83-0.96;
      p = 0.0018). In conclusion, we found that, when living with family, the lives of
      older adults can be extended by providing support, clearly supporting the old
      adage 'it is more blessing to give than to receive'. Older adults wanting to
      extend their lives can be encouraged to provide more help to their families.

PMID- 30210182
TI  - The intrinsic vulnerability of networks to epidemics.
AB  - Contact networks are convenient models to investigate epidemics, with nodes and
      links representing potential hosts and infection pathways, respectively. The
      outcomes of outbreak simulations on networks are driven both by the underlying
      epidemic model, and by the networks' structural properties, so that the same
      pathogen can generate different epidemic dynamics on different networks. Here we
      ask whether there are general properties that make a contact network
      intrinsically vulnerable to epidemics (that is, regardless of specific
      epidemiological parameters). By conducting simulations on a large set of modelled
      networks, we show that, when a broad range of network topologies is taken into
      account, the effect of specific network properties on outbreak magnitude is
      stronger than that of fundamental pathogen features such as transmission rate,
      infection duration, and immunization ability. Then, by focusing on a large set of
      real world networks of the same type (potential contacts between field voles,
      Microtus agrestis), we showed how network structure can be used to accurately
      assess the relative, intrinsic vulnerability of networks towards a specific
      pathogen, even when those have limited topological variability. These results
      have profound implications for how we prevent disease outbreaks; in many real
      world situations, the topology of host contact networks can be described and used
      to infer intrinsic vulnerability. Such an approach can increase preparedness and
      inform preventive measures against emerging diseases for which limited
      epidemiological information is available, enabling the identification of priority
      targets before an epidemic event.

PMID- 30210183
TI  - An Ode to Kirkland flap... Obituary to Modified Widman flap.

PMID- 30210181
TI  - Redefining Humicola sensu stricto and related genera in the Chaetomiaceae.
AB  - The traditional concept of the genus Humicola includes species that produce
      pigmented, thick-walled and single-celled spores laterally or terminally on
      hyphae or minimally differentiated conidiophores. More than 50 species have been
      described in the genus. Species commonly occur in soil, indoor environments, and
      compost habitats. The taxonomy of Humicola and morphologically similar genera is
      poorly understood in modern terms. Based on a four-locus phylogeny, the
      morphological concept of Humicola proved to be polyphyletic. The type of
      Humicola, H. fuscoatra, belongs to the Chaetomiaceae. In the Chaetomiaceae,
      species producing humicola-like thick-walled spores are distributed among four
      lineages: Humicola sensu stricto, Mycothermus, Staphylotrichum, and
      Trichocladium. In our revised concept of Humicola, asexual and sexually
      reproducing species both occur. The re-defined Humicola contains 24 species
      (seven new and thirteen new combinations), which are described and illustrated in
      this study. The species in this genus produce conidia that are lateral,
      intercalary or terminal on/in hyphae, and conidiophores are not formed or are
      minimally developed (micronematous). The ascospores of sexual Humicola species
      are limoniform to quadrangular in face view and bilaterally flattened with one
      apical germ pore. Seven species are accepted in Staphylotrichum (four new
      species, one new combination). Thick-walled conidia of Staphylotrichum species
      usually arise either from hyphae (micronematous) or from apically branched, seta
      like conidiophores (macronematous). The sexual morph represented by
      Staphylotrichum longicolleum (= Chaetomium longicolleum) produces ascomata with
      long necks composed of a fused basal part of the terminal hairs, and ascospores
      that are broad limoniform to nearly globose, bilaterally flattened, with an
      apical germ pore. The Trichocladium lineage has a high morphological diversity in
      both asexual and sexual structures. Phylogenetic analysis revealed four subclades
      in this lineage. However, these subclades are genetically closely related, and no
      distinctive phenotypic characters are linked to any of them. Fourteen species are
      accepted in Trichocladium, including one new species, twelve new combinations.
      The type species of Gilmaniella, G. humicola, belongs to the polyphyletic family
      Lasiosphaeriaceae (Sordariales), but G. macrospora phylogenetically belongs to
      Trichocladium. The thermophilic genus Mycothermus and the type species My.
      thermophilum are validated, and one new Mycothermus species is described.
      Phylogenetic analyses show that Remersonia, another thermophilic genus, is sister
      to Mycothermus and two species are known, including one new species. Thermomyces
      verrucosus produces humicola-like conidia and is transferred to Botryotrichum
      based on phylogenetic affinities. This study is a first attempt to establish an
      inclusive modern classification of Humicola and humicola-like genera of the
      Chaetomiaceae. More research is needed to determine the phylogenetic
      relationships of "humicola"-like species outside the Chaetomiaceae.

PMID- 30210184
TI  - Providing directions for the future through confronting challenges in our
      specialty.

PMID- 30210185
TI  - Efficacy of herbal dentifrice on the prevention of plaque and gingivitis as
      compared to conventional dentifrice: A systematic review and meta-analysis.
AB  - Objective: The aim of this study was to review literature on the effects of
      herbal dentifrice compared to conventional dentifrice on plaque and gingival
      inflammation. Materials and Methods: MEDLINE, Cochrane Central Register of
      Controlled Trials, and major journals were explored for studies up to September
      30, 2017. A comprehensive search was designed and the articles were independently
      screened for eligibility by two reviewers. Randomized controlled clinical trials,
      in which oral prophylaxis was undertaken before the intervention was introduced
      into the oral cavity using toothbrush were included. Where appropriate, a meta
      analysis (MA) was performed and standardized mean differences (SMDs) were
      calculated. Results: Ten articles out of 1378 titles were found to meet the
      eligibility criteria. A MA showed that for plaque intervention the SMD was 2.14;
      95% confidence interval (CI): 0.88-3.41, P = 0.0009; test for heterogeneity: P <
      0.00001, I2 = 96% in favor of conventional dentifrice; and for gingival
      inflammation, the SMD was 1.37; 95% CI: 0.49-2.26, P = 0.002; test for
      heterogeneity: P < 0.00001, I2 = 94% which also was in favor of conventional
      dentifrice. Subgroup analysis for plaque intervention and gingival inflammation
      in case of long-term (more than 4 weeks and up to 6 months) and short-term
      effects (minimum of 4 weeks) of herbal dentifrice showed no difference when
      compared to conventional dentifrice. Conclusion: Currently, there is no high
      quality evidence to support or abnegate the anti-plaque and anti-gingivitis
      effects of the herbal dentifrice.

PMID- 30210186
TI  - Osteoporosis effect on posterior mandible in preimplanted area for postmenopausal
      females using cone-beam computed tomography.
AB  - Background: Hormonal changes in women affect bone mineral density, especially
      during and postmenopausal years, which leads to susceptibility to osteoporosis
      which interfere with implantation. Aims: This study aims to use cone-beam
      computed tomography (CBCT) viewer program to predict patients with osteoporosis
      which may decrease the success rate of implantation and to evaluate osteoporosis
      effect on the posterior mandible. Settings and Design: This cross-sectional study
      consists of 60 Iraqi females who were divided into three groups: Group 1
      consisted of 20 nonosteoporotic females aged 20-30 years as a control group,
      Group 2 consisted of 20 nonosteoporotic females aged 50 years and above, and
      Group 3 consisted of 20 osteoporotic females aged 50 years and above. Materials
      and Methods: The posterior mandibular first molar area was examined for alveolar
      bone height and radiographic density (RD) using CBCT. Statistical Analysis Used:
      Statistical analysis was computer assisted using the Statistical Package for the
      Social Sciences (SPSS version 21). Interclass correlation coefficient was used
      for calibration. Normally distributed variables were assessed using one-way
      ANOVA, and Dunnett test with control and not normally distributed were assessed
      by Kruskal-Wallis test, and multiple Mann-Whitney U-test with Bonferroni
      adjustment. Results: RD showed a significant difference between Group 2 and Group
      3 (P = 0.000, MD = 158.554). On the other hand, alveolar bone height showed a
      significant difference between Group 1 and Group 2 (P = 0.039). Conclusions: RD
      in the posterior mandible first molar area is significantly affected in
      osteoporotic patients and it can be used as a predictor for the presence of
      osteoporosis using CBCT.

PMID- 30210188
TI  - Evaluation of periodontally diseased molars in diabetics with Miller-McEntire
      Periodontal Prognostic Index.
AB  - Aim and Objective: The aim of this study was to prospectively determine and
      establish the periodontal prognosis of diseased molars in diabetic patients using
      the Miller-McEntire Periodontal Prognostic Index (MMPPI) with an additional
      criterion for diabetes (changes in glycosylated hemoglobin levels), at 2-year
      postperiodontal therapy. Materials and Methods: A sample of 200 molars in 25
      patients with diabetes mellitus (DM) and chronic periodontitis were evaluated.
      The prognostic parameters evaluated include age, probing depth (PD), mobility,
      furcation involvement, diabetes, and molar type. The total score calculated from
      all parameters was used considered prognosis score for each molar. All patients
      were evaluated at baseline and 2-year posttreatment. Results: The results of this
      study suggest that following prognostic factors, DM (hazard ratio [HR] =5.2), age
      (HR = 0.4), and molar type (HR = 0.6) were clinically significant at the end of
      the 2-year posttherapy from baseline. A total of 4 (2%) teeth were extracted from
      the 200 teeth with a mean of 0.02 for the tooth lost during 2-year posttreatment.
      Significant improvements (P < 0.05) in the frequency PD, furcation, and mobility
      scores were noted at 2 years. Conclusions: These findings demonstrate that score
      for DM as prognostic criterion is a valid addition to MMPPI. The factors such as
      DM, age, and molar type can impact the prognosis of molar survival. Studies with
      a larger sample size and longer follow-up are required to affirm the findings of
      this preliminary study.

PMID- 30210187
TI  - Effect of hyperfunctional occlusal loads on periodontium: A three-dimensional
      finite element analysis.
AB  - Introduction: The periodontal tissue reaction to variations in occlusal forces
      has been described in the literature wherein clinical and histologic changes are
      discussed that produced due to stresses in the periodontal structures.
      Unfortunately, these stresses are not quantified. Aim: The aim of this study is
      to determine the stress produced on various periodontal tissues at different
      occlusal loads using finite element model (FEM) study. Materials and Methods:
      Four FEMs of maxillary incisor were designed consisting of the tooth, pulp,
      periodontal ligament (PDL), and alveolar bone at the various level of bone height
      (25%, 50%, and 75%). Different occlusal load (15 and 29 kg) at an angle of 50
      degrees  to the long axis of the tooth was applied on the palatal surface at the
      level of middle third of the crown. All the models were assumed to be isotropic,
      linear, and elastic, and the analysis was performed on a Pentium IV processor
      computer using the ANSYS software. Results: At normofunction load, the stresses
      were maximum on the mesial side near the cervical region at point D for tooth (
      10.93 Mpa) for PDL (-4.06 Mpa) for bone (-4.3 Mpa) with normal bone levels as the
      bone levels decreased the stresses increased and the stresses tend to concentrate
      at the apical region. At any given point, the stresses were increased by 90% at
      hyperfunctional load. Conclusion: Based on the findings of the present study,
      there is reasonably good attempt to express numerical data of stress to be given
      normal occlusal and hyperfunctional loads to simulate clinical occlusal
      situations which are known to be responsible for healthy and diseased
      periodontium.

PMID- 30210189
TI  - Treatment of horizontal defect with and without platelet-rich fibrin matrix: A
      randomized comparative clinical study.
AB  - Aim: The aim of the present study was to assess the clinical and radiographical
      parameters in horizontal bone defects in patients with chronic periodontitis.
      Materials and Methods: In this randomized, controlled clinical trial study, nine
      individuals with 94 sites having moderate to deep periodontitis were selected and
      distributed to Group A - open flap debridement (OFD), Group B - open flap
      debridement and intra marrow penetration (OFD + IMP) and Group C - Open flap
      debridement + Intramarrow penetration + platelet rich fibrin matrix (OFD + IMP +
      PRFM). Plaque index (PI) and gingival index (GI) were evaluated at baseline, 6
      months, and 9 months after surgery. Probing pocket depth (PPD) and clinical
      attachment level (CAL) were recorded at baseline and 9 months after surgery.
      Radiographic assessment was carried out to measure the periodontal defect depth
      and defect fill percentage (DF%) at baseline and 9 months after the surgery using
      radiovisiography. Results: The statistical evaluation obtained after 9 months
      showed no significant difference between PI and GI at 9 months interval.
      Intergroup comparison of PPD and CAL has shown significant difference in Group C
      as compared to Group A and B with P < 0.05. The defect depth was statistically
      significant at 9 months in all the groups, and DF percentage (DF%) has shown
      statistically significant results in Group C as compared to A and B with P = of
      0.001. Conclusion: The addition of PRFM to horizontal type of periodontal defects
      has shown promising results over a 9-month follow-up period.

PMID- 30210190
TI  - The comparison of two professional prophylaxis systems in plaque removal and
      debonding of orthodontic brackets.
AB  - Introduction: During orthodontic treatment, patients are expected to undergo
      consistent periodic prophylaxis as a result of complexities in oral hygiene. The
      aim of this study was to investigate, analyze, and compare the effectiveness of
      two professional prophylaxis systems of rubber cup polishing (RCP) and air-powder
      polishing (APP) in patients undergoing orthodontic treatment based on different
      levels of plaque and pigment on teeth and the extent of attachment of brackets
      after prophylaxis. Materials and Methods: A total of 50 patients were selected
      for this clinical trial study. A couple of months after the orthodontic
      treatment, the patients were placed on professional prophylaxis in terms of the
      plaque index. Randomized cross-arch prophylaxis (right maxilla with left
      mandible), RCP (left maxilla with right mandible), and APP were carried out on
      the patients. The main indexes in the study (number of plaque removal and
      debonding), the work time duration per second, and convenience of patients using
      visual analog scale in each of the methods were evaluated as minor factors. Data
      were recorded in a special checklist. Results: The mean of the plaque index and
      the time spent on RCP were observed to be higher than APP. The average
      satisfaction rate of patients with RCP was higher than APP. The debonding of the
      bracket and the tooth was not observed in any of the methods. Conclusion: APP is
      more efficient than RCP for performing professional prophylaxis of orthodontic
      patients.

PMID- 30210191
TI  - Effect of low-level laser therapy on wound healing and patients' response after
      scalpel gingivectomy: A randomized clinical split-mouth study.
AB  - Background: Low-level laser therapy (LLLT) is based on the principle of
      biostimulation or biomodulation effect. LLLT after gingivectomy has resulted in
      better wound healing because of its action on collagen synthesis, angiogenesis,
      and growth factor release. Aim: The aim of this split-mouth controlled clinical
      trial was to assess the effect of LLLT, using diode laser (InGaAsP), on wound
      healing and patients' response after scalpel gingivectomy. Materials and Methods:
      Forty patients with gingival enlargement in the maxillary and mandibular anterior
      region (bilaterally symmetrical) were included in the study. After gingivectomy,
      a diode laser (InGaAsP) was randomly applied to one side of the surgical area on
      the 1st, 3rd, and 7th day postoperatively. The surgical areas were disclosed by a
      solution (Alpha Plac(r)) to visualize the areas where the epithelium was absent.
      Comparison of the surface areas on the LLLT-applied sites and controls was made
      clinically by visualizing the stained area by two examiners. Results: LLLT
      applied sites had significantly lower stained areas signifying improved wound
      healing compared with the controls on the postoperative 7th and 30th day.
      Conclusion: Within the limitations of this study, the results indicated that LLLT
      might improve wound healing after gingivectomy.

PMID- 30210192
TI  - Comparative evaluation of efficacy of Murraya koenigii and chlorhexidine
      gluconate in the treatment of gingivitis: A randomized controlled clinical trial.
AB  - Background: Herbal products are widely substituting synthetic antimicrobials due
      to their minimal adverse effects and cost-effectiveness. Murraya koenigii (curry
      leaf) is an easily available green leafy vegetable, which is known for their
      antimicrobial, antioxidative, and cytotoxic activity. However, no published
      literature available evaluates their effectiveness in treating gingival
      inflammation. This study was aimed to evaluate the effectiveness of M. koenigii
      mouthwash in reduction of plaque and gingivitis in comparison with commercially
      available chlorhexidine (CHX) mouthwash. Materials and Methods: This single
      center, parallel-arm, randomized controlled clinical trial was carried out among
      individuals reported to the institution. A total of 45 participants with mild-to
      moderate gingivitis were selected and divided into three groups. Group A and B
      participants undergone scaling and were instructed to use M. koenigii and CHX
      mouthwashes, respectively. Group C participants have received only scaling. All
      the participants were recalled after 14 days of prescribed mouthwash use and
      clinical parameters were recorded. One-way analysis of variance test and
      Student's paired t-test were used for inter- and intra-group comparison of
      parameters, respectively. Results: On intragroup comparison of clinical
      parameters, all the three groups showed a statistically significant difference
      with P <= 0.05. On pairwise comparison, it showed a significant difference for
      Group B versus Group C and Group A versus Group C, while between Group A and
      Group B showed no significant difference. Conclusion: M. koenigii mouthwash is
      equally effective as CHX, in treating plaque-induced gingivitis.

PMID- 30210193
TI  - Evaluation of anti-inflammatory effect of chorion membrane in periodontal pocket
      therapy: A clinical and biochemical study.
AB  - Background: The aim of the study was to evaluate the anti-inflammatory effect of
      chorion as a barrier membrane in periodontal pocket therapy by assessing
      interleukin-11 (IL-11) level in gingival crevicular fluid (GCF). Materials and
      Methods: The study was a randomized, controlled, single-blind clinical trial with
      split-mouth design. In each patient, two sites in two quadrants were selected and
      randomly allocated in Group 1 (flap surgery) and Group 2 (flap surgery + chorion
      membrane placement). After Phase 1 therapy, clinical and biochemical parameters
      were recorded at baseline and at 4 weeks. Plaque index (PI), sulcus bleeding
      index (SBI), probing pocket depth (PPD), clinical attachment level (CAL), and IL
      11 in GCF were assessed. GCF was collected using microcapillary tubes. IL-11 was
      assayed in GCF with ELISA kit (Genxbio(r)). Results: At baseline, the clinical
      and the biochemical parameters were similar in both the groups. Intragroup
      comparison revealed statistically significant decrease in all clinical and
      biochemical parameters in Group 1 (P < 0.001) and Group 2 (P < 0.001). Intergroup
      comparison showed statistically significant decrease in SBI (P = 0.004), PPD (P =
      0.004), CAL (P = 0.013), and IL-11 (P = 0.006) in Group 2 compared to Group 1 at
      4 weeks. However, PI did not show any statistically significant difference on
      intergroup comparison. Conclusion: Adjunctive use of chorion membrane in flap
      surgery provides an additive anti-inflammatory effect along with improvement in
      clinical outcomes enhancing the long-term prognosis.

PMID- 30210194
TI  - A comparative study of synbiotic as an add-on therapy to standard treatment in
      patients with aggressive periodontitis.
AB  - Context: The role of synbiotic in the management of aggressive periodontitis (AP)
      is not well established. Aim: We designed this study to evaluate the efficacy and
      safety of synbiotic as an add-on therapy in the management of AP. Settings and
      Design: This was a randomized, double-blind, placebo-controlled study. Materials
      and Methods: Sixty patients with AP were randomized to two groups of 30 each.
      Study group received standard treatment, i.e., scaling and root planing along
      with doxycycline 100 mg twice daily for the 1st day (loading dose) followed by
      100 mg once daily for 1 week and synbiotic lozenge twice daily for 8 weeks,
      whereas control group received standard treatment for 1 week and placebo lozenge
      for 8 weeks. Clinical parameters were recorded at baseline, 4th, 8th, and 12th
      weeks. Statistical Analysis Used: Pearson's Chi-square test and one-way analysis
      of variance were used to analyze distribution of sex and age, respectively.
      Differences within the groups were analyzed by Student's paired t-test. Pearson's
      Chi-square test was applied to measure gingival bleeding index. Results: On
      comparison at 12 weeks, there was a statistically significant reduction (P <
      0.01) in probing depth, clinical attachment loss, oral hygiene index, and
      bleeding on probing in study group. No Adverse drug reactions were noted.
      Conclusion: Co-administration of synbiotic lozenge along with standard therapy is
      highly efficacious in improving periodontal health in patients with AP.

PMID- 30210195
TI  - Periodontal status in chronic periodontitis depressed patients on desvenlafaxine:
      An observational study.
AB  - Background: A wide variety of drugs have the potential to affect immune and
      inflammatory responses of periodontium. A class of antidepressant drug, selective
      serotonin and norepinephrine reuptake inhibitors, has shown anti-inflammatory
      function. The aim of the present study is to explore the effect of desvenlafaxine
      on clinical periodontal parameters in patients with chronic periodontitis.
      Materials and Methods: The patients were divided into two groups as follows: test
      group (n = 63) comprised of participants on 50 mg once-daily dose of
      desvenlafaxine for >=2 months and control group (n = 72) included participants
      who were yet to be prescribed medication for depression. Periodontal parameters
      of both the groups were analyzed and compared statistically. Results:
      Participants taking desvenlafaxine revealed lower values of periodontal
      parameters as compared to those in control group. The number of pockets with
      greater depth and clinical attachment loss was greater in control group.
      Conclusion: In our study, patients on desvenlafaxine were associated with less
      pocket depth and bleeding on probing.

PMID- 30210196
TI  - Knowledge, awareness, and practice among gynecologists, medical practitioners and
      dentists in Madurai regarding association between periodontitis and pregnancy
      outcomes.
AB  - Background: The prevalence of oral disease during pregnancy affects the health of
      the fetus and mother. The interdisciplinary protocol between general dentists
      (GDs), gynecologists, and general medical practitioners (GMPs) is proved to
      reduce the incidence of maternal and neonatal complications. Aim: The aim of the
      present survey is to assess the knowledge, awareness, and attitude of practicing
      gynecologists, GMPs, and GDs regarding the association of periodontitis and
      adverse pregnancy outcomes. Materials and Methods: This cross-sectional study was
      conducted among 150 health-care professionals in Madurai. A well-structured
      pretested questionnaire consisted of 12 questions which were used to assess the
      awareness of association regarding maintaining oral health during pregnancy among
      GMPs, GDs, and gynecologists. The knowledge, awareness, and practice scores were
      calculated for the correct answers to the questions. A software program (SPSS 12)
      was used for statistical analysis. Results: The mean age of participants was of
      33.14 +/- 1.5, 32.58 +/- 2.80, and 37.7 +/- 9.7, respectively. Majority of the
      participants agreed the importance of dental examination and maintaining oral
      health during pregnancy GMPs (96%), GDs (100%), and gynecologists (92%). About
      92% of gynecologists and GMPs supported that providing dental treatment during
      pregnancy improved pregnancy outcomes. About 64%, 76%, and 68% of GMPs, GDs, and
      gynecologists, respectively, confirmed the association between periodontal
      disease and adverse pregnancy outcomes. Conclusion: In this study, knowledge and
      awareness of gynecologists and GMPs are appreciable; however, their attitude
      toward bringing the facts into clinical practice needs to be improved through
      integrated programs.

PMID- 30210197
TI  - The socket-shield technique and immediate implant placement.
AB  - Healing of extraction socket leads to the dimensional changes which will affect
      the placement of the implant and its emergence profile. Atraumatic extraction,
      socket preservation technique, and immediate implant placement decrease the
      alveolar bone resorption by maintaining the postextraction socket. Hurzeler et
      al. introduced socket-shield technique by keeping a buccal fragment of the tooth
      to prevent the buccal cortical bone from resorption. This case report represents
      a 40-year-old male patient with grossly decayed maxillary left lateral incisor
      indicated for extraction replaced with an immediate implant. While examining cone
      beam computed tomography, thin buccal cortical plate was noticed which may get
      fracture during extraction. Socket-shield technique was designed for implant
      placement to protect buccal bone and to get the proper esthetic form. Two
      millimeters buccal fragment of the tooth was kept attached and the implant was
      placed in contact with tooth fragment. Three-month follow-up shows proper
      healing, and healthy peri-implant tissue shows that socket-shield technique with
      immediate implant placement will be a good alternative to preserve buccal
      cortical plate and implant placement, especially in the esthetic area.

PMID- 30210198
TI  - A novel clinical protocol for the greater palatine compression suture: A case
      report.
AB  - Bleeding from the palatal donor site is a worrisome complication of palatal soft
      tissue harvesting procedures and leads to considerable stress to both the patient
      and the surgeon. Several methods to control palatal hemorrhage have been
      suggested in literature, including a palatal suture, but a precise protocol has
      not been suggested. The present case report aims to suggest a protocol for the
      greater palatine compression suture (GPCS). Five patients who experienced profuse
      bleeding from the palatal free gingival graft donor site were treated with the
      GPCS. The palatal midline was used as a landmark and the location of the greater
      palatine foramen was estimated. The suture was placed anterior to the estimated
      location of the foramen and was passed deep into the palatal tissue with the aim
      of looping and compressing the vascular bundle. In all the patients, an immediate
      reduction and arrest of bleeding from the palatal wound was observed with
      blanching of the soft tissues around the suture. The proposed technique is a
      predictable method to control palatal hemorrhage and can be used if other less
      invasive techniques fail to stem the blood flow from an injured palatal vessel.

PMID- 30210199
TI  - Periodontally accelerated osteogenic orthodontics: Novel perio-ortho
      interrelationship.
AB  - Periodontally accelerated osteogenic orthodontics (PAOO) is a clinical procedure
      that incorporates selective corticotomy, particulate grafting, and application of
      optimal orthodontic forces. It reduces treatment time, increases stability of
      teeth, and prevents relapse of orthodontic tooth movement (OTM). The present case
      report highlights the technique and principles of PAOO for rapid OTM.

PMID- 30210200
TI  - CT-measurement predicts shortening of stable intertrochanteric hip fractures.
AB  - Purpose: Intertrochanteric (IT) hip fractures can be treated with sliding hip
      screws (SHS) or cephalomedullary nails (CMN) based on the stability of the
      fracture. This stability is affected by the initial impaction of the fracture
      which can be difficult to assess. The aim of this paper is to develop specific
      pre-operative computed tomography (CT) measurements of IT fractures which are
      predictive of post-operative shortening. Methods: A retrospective review was
      performed of 141 patients with AO/OTA 31A1 or 31A2 fracture patterns, who had pre
      operative radiographs and CT scans, and who were treated with a SHS or a CMN. Pre
      operative and post-operative imaging of IT fractures were analyzed for those
      fractures that shortened >=15 mm post-fixation. Results: 11 fractures shortened
      >=15 mm with CMN being protective of shortening (6/36 SHS versus 5/105 CMN, p =
      0.0268). A novel measurement made on the pre-operative CT scan called the
      cortical thin point (CTP) detected differences between patients with <15 mm and
      >=15 mm of post-operative shortening for the SHS group (p = 0.0375). CTP was
      found to be a reliable predictor for post-operative shortening of >=15 mm when a
      cutoff threshold of 9 mm was used in the SHS group (p = 0.0161). Conclusions:
      Measuring the CTP is predictive of post-operative shortening after fixation of an
      IT fracture with a SHS. CMN fixation may be protective of shortening. Patients
      with a CTP of <=9 mm are at risk for fracture site shortening of more than 15 mm
      when treated with a SHS.

PMID- 30210201
TI  - Options and limits of angle stable plates in the treatment of comminuted radial
      head fractures.
AB  - Objective: New angle-stable plates provide more stability and better anatomical
      fit than previous plates. Methods: 22 patients treated with an angle-stable plate
      were included. Postoperative the outcomes were evaluated according to the scoring
      systems of Morrey, Radin and Riseborough. Results: 3 patients received a score of
      excellent, 14 good, and 5 satisfactory. We detected 3 cases of implant failure
      and 2 cases of postoperative neurological damage. 3 patientes received a radial
      head necrosis. Conclusions: Our results show that the angle-stable radial head
      locking plate can only be used in limited cases in the treatment of multi
      fragment radial head fractures.

PMID- 30210202
TI  - Clear cell sarcoma-A review.
AB  - Clear cell sarcoma (CCS) previously known as malignant melanoma (MM) of the soft
      tissue, although, similar in morphology to MM, contemporary histopathologic and
      cytogenetic techniques have made this diagnosis obsolete, as it is now possible
      to distinguish between CCS and MM. CCS is often diagnosed in young adults with
      median age of 25 years. Overall mortality is generally poor, and the 5-year
      survival is between 40 and 60%. Hence, early diagnosis and radical surgery are
      key in the treatment of this extremely rare malignancy of the soft tissue
      comprising only about 1% of all sarcomas. This article present an overview of
      this rare malignancy.

PMID- 30210204
TI  - Trends for Facial Injectable Therapies in Medical Aesthetics.

PMID- 30210203
TI  - 3D reconstruction does not improve agreement and results in an increase in
      surgical indications in proximal humeral fractures.
AB  - The objective of this study is to analyze the effect of different imaging
      modalities in treatment decision making in proximal humeral fractures. After
      evaluation of 116 consecutive proximal humeral fractures, observers were asked to
      give treatment recommendation (conservative vs. surgery). If surgery was
      proposed, they were told to select surgery of choice. When 3D imaging was added,
      complexity of fractures significantly increased (p < 0.001), number of surgeries
      significantly increased (p < 0.000) and number of ORIF treatments significantly
      increased (p < 0.0004). Addition of 3D imaging of proximal humeral fractures
      significantly increases number of surgical decisions when compared to radiographs
      alone or together with CT.

PMID- 30210205
TI  - Dynamic Relaxers of the Face.
AB  - Dynamics of the facial aesthetics is changing rapidly as we treat more and more
      faces. Our understanding of the molecule at hand and its various applications
      only expands as our learnings progress. Perception and expectation of the end
      goal to beauty itself are evolving, and therefore newer ways of analyzing,
      understanding, and delivering of any aesthetic drug have to evolve continuously.
      Botulinum toxin is one of the wonders in the aesthetic world, which led the
      entire focus of the medical fraternity into nonsurgical facial aesthetics.
      Botulinum toxin was and is still the best tool for relaxing lateral canthal lines
      and glabellar frown lines. However, it has evolved further to now impart
      changes/enhancements in skin texture and luminosity, enhancement in facial shape,
      and reduction in glandular activity of sebaceous, sweat, and salivary glands,
      therefore leading to a lot more aesthetic application while it still remains as
      the line eraser.

PMID- 30210206
TI  - Simplifying Injectables for Volumetric Rejuvenation of Face.
AB  - Volumetric rejuvenation with fillers is a minimally invasive technique used for
      facial volume restoration. Volume restoration demands adequate knowledge of fat
      pads and vascularity of the face and the understanding of the depletion patterns.
      Volumetric restoration with injectable has witnessed a paradigm shift in the last
      decade with a global rejuvenation, acquiring a predominant emphasis over focal
      wrinkle filling to restore the depletion pattern of facial fat layers. The
      techniques used to achieve optimal restoration of facial volume revolve around
      zonal lifting and tenting, and the impact of treatment on one zone of the
      surrounding zones is crucial. A face mapping performed for filler technique has
      thus evolved, with many experts advocating varied techniques from global
      restoration to point lifts at key areas, to improve the outcome of filler
      injections, albeit safely, thus simplifying the process. A systematic approach to
      various techniques and the point lifts in various zones pertaining to the face
      structure in the Indian skin are highlighted in this article.

PMID- 30210207
TI  - Beware What You Inject: Complications of Injectables-Dermal Fillers.
AB  - Cosmetic filler injections are most popular among the antiaging procedures. As in
      any other cosmetic injectable procedures, complications are likely to occur even
      under experienced hands. However, it is the duty of the aesthetic physician to
      identify and manage these potential complications. The objective of this symposia
      is to help the aesthetic physician to identify these complications early and
      manage them appropriately to improve outcomes.

PMID- 30210208
TI  - Fat Busters: Lipolysis for Face and Neck.
AB  - Persistence and hypertrophy of fat pads particularly of the face and neck region
      disturb beauty proportions, thus demand treatments. Phosphatidylcholine and
      deoxycholic acid are the most commonly used solutions for injection lipolysis. As
      we stand today, sodium deoxycholate preparation is approved by the US Food and
      Drug Administration for the same. This article describes the correct use of
      solution to achieve fat reduction and ensure safety. Complete details of patient
      selection, assessment, dosing, and injection techniques are described in this
      article. A brief note on posttreatment care and complications is also provided.

PMID- 30210210
TI  - Anatomy and Applications of the #15 Scalpel Blade and Its Variations.
AB  - Scalpels have been used to make skin incisions since the advent of "modern"
      dermatosurgery. #15 Scalpel blade and #3 handle (Bard-Parker handle) are most
      frequently used by a dermatosurgeon. Besides the proper equipment, appropriate
      technique is mandatory to ensure a "precise" incision. In this article, we
      discuss about the anatomy, variations, and different uses of the #15 scalpel
      blade and the ideal method of making a "precise" skin incision.

PMID- 30210209
TI  - Arm Contouring After Massive Weight Loss: Liposuction-Assisted Brachioplasty
      Versus Standard Technique.
AB  - Massive weight loss (MWL) brachioplasty is frequently requested for the
      improvement of the appearance and function of arms. Despite its diffusion, this
      procedure can be associated with significant complications. Liposuction-assisted
      brachioplasty (LAB) preserves the vascular, nervous, and lymphatic network and
      reduces the incidence of postoperative complications. This retrospective cohort
      study is aimed at analyzing two different modalities of arm contouring after MWL
      by evaluating the outcomes and complications. Of 31 patients (all females,
      average age 43.5 years), 20 were managed with standard brachioplasty represented
      by a swallowtail scar and monobloc resection and 11 with brachioplasty combined
      with aggressive liposuction. Evaluated parameters included age, body mass index,
      method of weight loss, and complications rate. No statistical analysis was used.
      Major postoperative complications (reoperation, bleeding, or thromboembolism)
      were not reported in both groups. The incidence of minor complications (wound
      separation, wound infection, and seroma) was globally 42%; the incidence of
      complications was significantly lower in the LAB group (9% vs. 60%). The
      incidence of hypertrophic scarring or keloid was higher in the control group (55%
      vs. 18%). Most patients were satisfied after surgery: in the LAB group, 81.8% of
      the patients expressed a high degree of satisfaction and 18.2% a good degree of
      satisfaction after 4 months of follow-up. In our experience, the LAB should be
      preferred in MWL patients because it has a lower rate of complications and a
      faster recovery than the standard technique. Proper execution requires
      considerable technical skill and experience.

PMID- 30210211
TI  - An Innovative Training Model for Practicing Hairline Designing.
AB  - Hair transplantation has undergone a massive transformation in todays world.
      Besides advancement in technique there has also been a great increase in the
      demand for hair transplant. This rise in demand for hair transplant has further
      led to an increase in the requirement of professionally trained hair transplant
      surgeons. In this article we have described a new, versatile and simple technique
      for hair transplant surgeons to effectively practice hair line designing. This
      innovative technique proves vital in perfecting the art of the recipient area
      designing for the hairline, eyebrow, beard etc. for a surgeon who is undergoing
      training as well as for previously trained surgeons to rehearse an old skill to
      gain further confidence. Besides helping us practice the art of hairline
      designing this technique also teaches us the correct angle, direction, depth and
      density of slits which are ideal and thus helps us to be better prepared for the
      real life scenario.

PMID- 30210212
TI  - Innovative Use of Abdominoplasty Specimen.
AB  - Simulator training is important for understanding nipple-areolar complex
      reconstruction. Human tissue is the best tissue simulator for surgical training.
      Abdominoplasty specimen is a useful tissue simulator, which is suitable for
      practicing nipple-areolar complex reconstruction. It is similar to the natural
      mound created in breast reconstruction. Authors have shared their experience of
      using abdominoplasty specimen for simulator training of nipple-areolar complex
      reconstruction for plastic surgery residents. Abdominoplasty specimen is cost
      effective, readily available, and an efficient tool for plastic surgery training
      for the residents.

PMID- 30210213
TI  - Lipoid Proteinosis: Skin Resurfacing with Combination of Fractional CO2 and Non
      ablative Radio Frequency: A Rare Case Report.
AB  - Lipoid proteinosis (LP) is a rare autosomal-recessive genodermatosis,
      characterized by the deposition of amorphous hyaline-like material in different
      parts of the body, especially the skin and mucous membranes. Disfiguring lesions
      predominantly affect the facial appearance. No curative therapy and treatment
      options limited to symptomatic approaches are available. Facial disfigurement in
      this disease may have a huge negative effect on the patients' psychology and
      quality of life. With this regard, the patients may benefit very much from the
      treatments that enhance their cosmetic outlook. We present a 19-year-old female
      patient with LP who came to us seeking treatment for her facial lesions. She was
      treated with a combination regimen of fractional carbon dioxide and non-ablative
      radio frequency with good clinical and aesthetic outcome.

PMID- 30210214
TI  - Multiple Miliary Osteoma Cutis of Face.
AB  - Multiple miliary osteoma cutis is an uncommon condition presenting as multiple
      skin-colored papules of variable sizes on the face. A 48-year-old woman presented
      with multiple skin-colored hard papules on both cheeks. Examination revealed firm
      to-hard dome-shaped asymptomatic papules in cluster over both cheeks. A punch
      biopsy was performed, which showed evidence of focal bony trabeculae with
      associated normal appendages. Few larger papules were incised and followed up
      with curettage of bony material and closed. All lesions could not be incised and
      removed because of large number of lesions in cluster.

PMID- 30210215
TI  - A Simple, Efficient, and Economical Head Drape Technique for Facial Procedures:
      The Nun's Veil Drape.

PMID- 30210216
TI  - Dermatological Surgery in Patients with Cardiac Implantable Electronic Devices: A
      New Paradigm.

PMID- 30210217
TI  - 29th National Dermatology Congress of the Algerian Society of Dermatology
      Algiers, October 18 and 19, 2017.

PMID- 30210218
TI  - Application of quantitative imaging in oncologic management.

PMID- 30210219
TI  - Radiomics approach for preoperative identification of stages I-II and III-IV of
      esophageal cancer.
AB  - Objective: To predict preoperative staging using a radiomics approach based on
      computed tomography (CT) images of patients with esophageal squamous cell
      carcinoma (ESCC). Methods: This retrospective study included 154 patients
      (primary cohort: n=114; validation cohort: n=40) with pathologically confirmed
      ESCC. All patients underwent a preoperative CT scan from the neck to abdomen.
      High throughput and quantitative radiomics features were extracted from the CT
      images for each patient. A radiomics signature was constructed using the least
      absolute shrinkage and selection operator (Lasso). Associations between radiomics
      signature, tumor volume and ESCC staging were explored. Diagnostic performance of
      radiomics approach and tumor volume for discriminating between stages I-II and
      III-IV was evaluated and compared using the receiver operating characteristics
      (ROC) curves and net reclassification improvement (NRI). Results: A total of
      9,790 radiomics features were extracted. Ten features were selected to build a
      radiomics signature after feature dimension reduction. The radiomics signature
      was significantly associated with ESCC staging (P<0.001), and yielded a better
      performance for discrimination of early and advanced stage ESCC compared to tumor
      volume in both the primary [area under the receiver operating characteristic
      curve (AUC): 0.795vs. 0.694, P=0.003; NRI=0.424)] and validation cohorts (AUC:
      0.762 vs. 0.624, P=0.035; NRI=0.834). Conclusions: The quantitative approach has
      the potential to identify stage I-II and III-IV ESCC before treatment.

PMID- 30210220
TI  - Computed tomography-based radiomics for prediction of neoadjuvant chemotherapy
      outcomes in locally advanced gastric cancer: A pilot study.
AB  - Objective: The standard treatment for patients with locally advanced gastric
      cancer has relied on perioperative radio-chemotherapy or chemotherapy and
      surgery. The aim of this study was to investigate the wealth of radiomics for pre
      treatment computed tomography (CT) in the prediction of the pathological response
      of locally advanced gastric cancer with preoperative chemotherapy. Methods:
      Thirty consecutive patients with CT-staged II/III gastric cancer receiving
      neoadjuvant chemotherapy were enrolled in this study between December 2014 and
      March 2017. All patients underwent upper abdominal CT during the unenhanced, late
      arterial phase (AP) and portal venous phase (PP) before the administration of
      neoadjuvant chemotherapy. In total, 19,985 radiomics features were extracted in
      the AP and PP for each patient. Four methods were adopted during feature
      selection and eight methods were used in the process of building the classifier
      model. Thirty-two combinations of feature selection and classification methods
      were examined. Receiver operating characteristic (ROC) curves were used to
      evaluate the capability of each combination of feature selection and
      classification method to predict a non-good response (non-GR) based on tumor
      regression grade (TRG). Results: The mean area under the curve (AUC) ranged from
      0.194 to 0.621 in the AP, and from 0.455 to 0.722 in the PP, according to
      different combinations of feature selection and the classification methods. There
      was only one cross-combination machine-learning method indicating a relatively
      higher AUC (>0.600) in the AP, while 12 cross-combination machine-learning
      methods presented relatively higher AUCs (all >0.600) in the PP. The feature
      selection method adopted by a filter based on linear discriminant analysis +
      classifier of random forest achieved a significantly prognostic performance in
      the PP (AUC, 0.722+/-0.108; accuracy, 0.793; sensitivity, 0.636; specificity,
      0.889; Z=2.039; P=0.041). Conclusions: It is possible to predict non-GR after
      neoadjuvant chemotherapy in locally advanced gastric cancers based on the
      radiomics of CT.

PMID- 30210221
TI  - Radiomic analysis of pulmonary ground-glass opacity nodules for distinction of
      preinvasive lesions, invasive pulmonary adenocarcinoma and minimally invasive
      adenocarcinoma based on quantitative texture analysis of CT.
AB  - Objective: To identify the differences among preinvasive lesions, minimally
      invasive adenocarcinomas (MIAs) and invasive pulmonary adenocarcinomas (IPAs)
      based on radiomic feature analysis with computed tomography (CT). Methods: A
      total of 109 patients with ground-glass opacity lesions (GGOs) in the lungs
      determined by CT examinations were enrolled, all of whom had received a
      pathologic diagnosis. After the manual delineation and segmentation of the GGOs
      as regions of interest (ROIs), the patients were subdivided into three groups
      based on pathologic analyses: the preinvasive lesions (including atypical
      adenomatous hyperplasia and adenocarcinoma in situ) subgroup, the MIA subgroup
      and the IPA subgroup. Next, we obtained the texture features of the GGOs. The
      data analysis was aimed at finding both the differences between each pair of the
      groups and predictors to distinguish any two pathologic subtypes using logistic
      regression. Finally, a receiver operating characteristic (ROC) curve was applied
      to accurately evaluate the performances of the regression models. Results: We
      found that the voxel count feature (P<0.001) could be used as a predictor for
      distinguishing IPAs from preinvasive lesions. However, the surface area feature
      (P=0.040) and the extruded surface area feature (P=0.013) could be predictors of
      IPAs compared with MIAs. In addition, the correlation feature (P=0.046) could
      distinguish preinvasive lesions from MIAs better. Conclusions: Preinvasive
      lesions, MIAs and IPAs can be discriminated based on texture features within CT
      images, although the three diseases could all appear as GGOs on CT images. The
      diagnoses of these three diseases are very important for clinical surgery.

PMID- 30210222
TI  - Differential study of DCE-MRI parameters in spinal metastatic tumors, brucellar
      spondylitis and spinal tuberculosis.
AB  - Objective: In the present study, spinal metastatic tumors, brucellar spondylitis
      and spinal tuberculosis were quantitatively analyzed using dynamic contrast
      enhanced magnetic resonance imaging (DCE-MRI) to assess the value of DCE-MRI in
      the differential diagnosis of these diseases. Methods: Patients with brucellar
      spondylitis, spinal tuberculosis or a spinal metastatic tumor (30 cases of each)
      received conventional MRI and DCE-MRI examination. The volume transfer constant
      (Ktrans), rate constant (Kep), extravascular extracellular volume fraction (Ve)
      and plasma volume fraction (Vp) of the diseased vertebral bodies were measured on
      the perfusion parameter map, and the differences in these parameters between the
      patients were compared. Results: For pathological vertebrae in cases of spinal
      metastatic tumor, brucellar spondylitis and spinal tuberculosis, respectively,
      the Ktrans values (median +/- quartile pitch) were 0.989+/-0.014, 0.720+/-0.011
      and 0.317+/-0.005 min-1; the Kep values were 2.898+/-0.055, 1.327+/-0.017 and
      0.748+/-0.006 min-1; the Ve values were 0.339+/-0.008, 0.542+/-0.013 and 0.428+/
      0.018; the Vp values were 0.048+/-0.008, 0.035+/-0.004 and 0.028+/-0.009; the
      corresponding H values were 50.25 (for Ktrans), 52.47 (for Kep), 48.33 (for Ve)
      and 46.56 (for Vp), and all differences were statistically significant (two-sided
      P<0.05). Conclusions: The quantitative analysis of DCE-MRI has a certain value in
      the differential diagnosis of spinal metastatic tumor, brucellar spondylitis and
      spinal tuberculosis.

PMID- 30210223
TI  - A radiomic nomogram based on an apparent diffusion coefficient map for
      differential diagnosis of suspicious breast findings.
AB  - Objective: To develop and validate a radiomic nomogram based on an apparent
      diffusion coefficient (ADC) map for differentiating benign and malignant lesions
      in suspicious breast findings classified as Breast Imaging Reporting and Data
      System (BI-RADS) category 4 on breast magnetic resonance imaging (MRI). Methods:
      Eighty-eight patients diagnosed with BI-RADS 4 findings on breast MRI in the
      First Affiliated Hospital of China Medical University from December 2014 to
      December 2015 were retrospectively analyzed in this study. Sixty-three were
      randomized electronically to establish forecasting models, and the other 25 were
      used for validation. Radiomic features based on the ADC map were generated
      automatically by Artificial Intelligence Kit software (A.K. software; GE
      Healthcare, China). Feature reduction was conducted using the Mann-Whitney test
      and Spearman correlation after pre-treatment. A prediction model of ADC radiomics
      was established by logistic linear regression and cross-validation. A nomogram
      was established based on ADC radiomic features, pharmacokinetics and clinical
      features, including the morphology and ADC value for breast BI-RADS 4 lesions on
      MRI. Results: A total of 396 radiomic features were extracted automatically by
      the A.K. software. Five features were selected after pre-processing, Mann-Whitney
      tests and Spearman correlation analysis. The area under the ROC curve of the
      prediction model comprising ADC radiomic features was 0.79 when the cutoff value
      was 0.45, and the accuracy, sensitivity and specificity were 80.0%, 0.813 and
      0.778, respectively. A visualized differential nomogram based on the radiomic
      score, pharmacokinetics and clinical features was established. The decision curve
      showed good consistency. Conclusions: ADC radiomic features could provide an
      important reference for differential diagnosis between benign and malignant
      lesions in suspicious BI-RADS 4 lesions. The visualized nomogram based on ADC
      radiomic features, pharmacokinetics and clinical features may have good prospects
      for clinical application.

PMID- 30210224
TI  - Annual cost of illness of stomach and esophageal cancer patients in urban and
      rural areas in China: A multi-center study.
AB  - Objective: Stomach and esophageal cancer are imposing huge threats to the health
      of Chinese people whereas there were few studies on the financial burden of the
      two cancers. Methods: Costs per hospitalization of all patients with stomach or
      esophageal cancer discharged between September 2015 and August 2016 in seven
      cities/counties in China were collected, together with their demographic
      information and clinical details. Former patients in the same hospitals were
      sampled to collect information on annual direct non-medical cost, indirect costs
      and annual number of hospitalization. Annual direct medical cost was obtained by
      multiplying cost per hospitalization by annual number of hospitalization. Annual
      cost of illness (ACI) was obtained by adding the average value of annual direct
      medical cost, direct non-medical cost and indirect cost, stratified by sex, age,
      clinical stage, therapy and pathologic type in urban and rural areas. Costs per
      hospitalization were itemized into eight parts to calculate the proportion of
      each part. All costs were converted to 2016 US dollars (1 USD=6.6423 RMB).
      Results: Totally 19,986 cases were included, predominately male. Mean ages of
      stomach cancer and urban patients were lower than that of esophageal cancer and
      rural patients. ACI of stomach and esophageal cancer patients were $10,449 and
      $13,029 in urban areas, and $2,927 and $3,504 in rural areas, respectively.
      Greater ACI was associated with male, non-elderly patients as well as those who
      were in stage I and underwent surgeries. Western medicine fee took the largest
      proportion of cost per hospitalization. Conclusions: The ACI of stomach and
      esophageal cancer was tremendous and varied substantially among the population in
      China. Preferential policies of medical insurance should be designed to tackle
      with this burden and further reduce the health care inequalities.

PMID- 30210225
TI  - A nomogram to predict prognosis for gastric cancer with peritoneal dissemination.
AB  - Objective: To identify independent prognostic factors to be included in a
      nomogram to predict the prognosis of gastric cancer patients with peritoneal
      dissemination. Methods: This is a retrospective study on 684 patients with a
      histological diagnosis of gastric cancer with peritoneal dissemination from the
      Sun Yat-sen University Cancer Center as the development set, and 62 gastric
      cancer patients from the Sixth Affiliated Hospital of Sun Yat-sen University as
      the validation group. Chi-square test and Cox regression analysis were used to
      compare the clinicopathological variables and the prognosis of gastric cancer
      patients with peritoneal dissemination. The Harrell's concordance index (C-index)
      and calibration curve were determined for comparisons of predictive ability of
      the nomogram. Results: Univariate and multivariate analyses showed that serum
      carcinoembryonic antigen (CEA) level (P=0.032), ascites grading (P=0.008),
      presence of extraperitoneal metastasis (P<0.001), seeding status (P=0.016) and
      performance status (P=0.009) were independent prognostic factors for gastric
      cancer patients with peritoneal dissemination in the development set. The
      nomogram model was constructed using these five factors. Internal validation
      showed that the C-index of the model was 0.641. For the external validation, the
      C-index of this model was 0.709. Conclusions: We developed and validated a
      nomogram to predict the prognosis for gastric cancer patients with peritoneal
      dissemination. This nomogram may play an important clinical role in guiding
      palliative therapy for these types of patients, although it may need more data
      for optimization.

PMID- 30210226
TI  - Increased incidence of chemoport-related thrombosis in patients with colorectal
      cancer receiving bevacizumab: A single-institutional experience.
AB  - Objective: Chemoport-related thrombosis (CRT) is a serious complication that
      causes morbidities and interrupts administration of intravenous cancer therapy.
      We investigated the incidence and risk of CRT in colorectal cancer (CRC) patients
      treated with bevacizumab (BEV). Methods: We retrospectively reviewed 1,534 CRC
      patients who received chemotherapy with or without BEV using a chemoport between
      2014 and 2016. Results: The participants had a median age of 58 (18-85) years,
      and 60.3% were male. All participants were stratified into three groups: adjuvant
      chemotherapy (AC) (n=670), palliative chemotherapy (PC) without BEV (n=356), and
      PC with BEV (n=508). The median follow-up was 20.19 (interquartile range, 14.07
      27.19) months. CRT occurred in 3.8% of all patients; incidence of symptomatic and
      asymptomatic CRT was 2.9% and 0.9%, respectively. CRT occurred more in patients
      with BEV (5.7%) than in patients without BEV (2.9%, P=0.008). The cumulative
      incidence of CRT in patients administered PC with BEV was significantly higher
      than that in those administered AC (P=0.011) and there was a trend toward
      increased CRT in patients administered PC with BEV compared with those
      administered PC without BEV (P=0.044). Multivariate analysis found that BEV
      treatment was the only variable that was significantly associated with CRT
      (hazard ratio, 2.06; 95% confidence interval, 1.24-3.43; P=0.006). Conclusions:
      BEV treatment was significantly associated with increased incidence of CRT in CRC
      patients.

PMID- 30210227
TI  - Evaluation of menopausal status among breast cancer patients with chemotherapy
      induced amenorrhea.
AB  - Objective: In patients with chemotherapy-induced amenorrhea (CIA), the menopausal
      status is ambiguous and difficult to evaluate. This study aimed to establish a
      discriminative model to predict and classify the menopausal status of breast
      cancer patients with CIA. Methods: This is a single center hospital-based study
      from 2013 to 2016. The menopausal age distribution and accumulated incidence rate
      of CIA are described. Multivariate models were adjusted for established and
      potential confounding factors including age, serum concentration of estradiol
      (E2) and follicle-stimulating hormone (FSH), feeding, pregnancy, parity,
      abortions, and body mass index (BMI). The odds ratio (OR) and 95% confidence
      interval (95% CI) of different risk factors were estimated. Results: A total of
      1,796 breast cancer patients were included in this study, among whom, 1,175
      (65.42%) were premenopausal patients and 621 (34.58%) were post-menopause
      patients. Five hundred and fifty patients were included in CIA analysis, and a
      cumulative CIA rate of 81.64% was found in them. Age (OR: 1.856, 95% CI: 1.732
      1.990), serum concentration of E2 (OR: 0.976, 95% CI: 0.972-0.980) and FSH (OR:
      1.060, 95% CI: 1.053-1.066), and menarche age (OR: 1.074, 95% CI: 1.009-1.144)
      were found to be associated with the patients' menopausal status. According to
      multivariate analysis, the discriminative model to predict the menopausal status
      is Logit (P)=-28.396+0.536Age-0.014E2+0.031FSH. The sensitivities for this model
      were higher than 85%, and its specificities were higher than 89%. Conclusions:
      The discriminative model obtained from this study for predicting menstrual state
      is important for premenopausal patients with CIA. This model has high specificity
      and sensitivity and should be prudently used.

PMID- 30210228
TI  - Focal Epilepsy and the Clock Gene.
AB  - Investigators from Children's National Medical Center, Wenzhou Medical
      University, Virginia Tech, University of Colorado, University of Virginia,
      Georgetown University, University of Maryland, and Brown University performed
      transcriptome analysis on human epileptogenic tissue and extended the
      investigation by creating and testing mouse lines with targeted genetic deletions
      of the Clock gene.

PMID- 30210229
TI  - Pharmacokinetics and Optimal Dosing of Phenobarbital.
AB  - Researchers from the Baylor College of Medicine in Houston, TX, USA, conducted a
      retrospective population pharmacokinetic analysis of 355 patients ages less than
      19 years of age in the inpatient setting who were initiated on intravenous or
      oral phenobarbital therapy and had one or more serum phenobarbital concentrations
      sampled.

PMID- 30210231
TI  - Novel homozygous splicing mutations in ARL2BP cause autosomal recessive retinitis
      pigmentosa.
AB  - Purpose: Mutations in ARL2BP, encoding ADP-ribosylation factor-like 2 binding
      protein, have recently been implicated as a cause of autosomal recessive
      retinitis pigmentosa (arRP), with three homozygous variants identified to date.
      In this study, we performed next-generation sequencing to reveal additional arRP
      cases associated with ARL2BP variants. Methods: Whole-genome sequencing (WGS) or
      whole-exome sequencing (WES) was performed in 1,051 unrelated individuals
      recruited for the UK Inherited Retinal Disease Consortium and NIHR-BioResource
      Rare Diseases research studies. Sanger sequencing was used to validate the next
      generation sequencing data, and reverse transcriptase (RT)-PCR analysis was
      performed on RNA extracted from blood from affected individuals to test for
      altered splicing of ARL2BP. Detailed phenotyping was performed, including
      clinical evaluation, electroretinography, fundus photography, fundus
      autofluorescence imaging, and spectral-domain optical coherence tomography.
      Results: Homozygous variants in ARL2BP (NM_012106.3) were identified in two
      unrelated individuals with RP. The variants, c.207+1G>A and c.390+5G>A, at
      conserved splice donor sites for intron 3 and intron 5, respectively, were
      predicted to alter the pre-mRNA splicing of ARL2BP. RT-PCR spanning the affected
      introns revealed that both variants caused abnormal splicing of ARL2BP in samples
      from affected individuals. Conclusions: This study identified two homozygous
      variants in ARL2BP as a rare cause of arRP. Further studies are required to
      define the underlying disease mechanism causing retinal degeneration as a result
      of mutations in ARL2BP and any phenotype-genotype correlation associated with
      residual levels of the wild-type transcript.

PMID- 30210232
TI  - Systematic Identification and Classification of beta-Lactamases Based on Sequence
      Similarity Criteria: beta-Lactamase Annotation.
AB  - beta-lactamases, the enzymes responsible for resistance to beta-lactam
      antibiotics, are widespread among prokaryotic genera. However, current beta
      lactamase classification schemes do not represent their present diversity. Here,
      we propose a workflow to identify and classify beta-lactamases. Initially, a set
      of curated sequences was used as a model for the construction of profiles Hidden
      Markov Models (HMM), specific for each beta-lactamase class. An extensive,
      nonredundant set of beta-lactamase sequences was constructed from 7 different
      resistance proteins databases to test the methodology. The profiles HMM were
      improved for their specificity and sensitivity and then applied to fully
      assembled genomes. Five hierarchical classification levels are described, and a
      new class of beta-lactamases with fused domains is proposed. Our profiles HMM
      provide a better annotation of beta-lactamases, with classes and subclasses
      defined by objective criteria such as sequence similarity. This classification
      offers a solid base to the elaboration of studies on the diversity, dispersion,
      prevalence, and evolution of the different classes and subclasses of this
      critical enzymatic activity.

PMID- 30210233
TI  - Evaluating a Dyadic Intervention on Risk Reduction Among People Who Inject Drugs.
AB  - Among 100 people who inject drugs enrolled in a peer mentorship intervention
      aiming to promote injection-related risk reduction behavior change, we evaluated
      the role of participation in a dyad session on reducing sharing of syringes and
      cookers in the past 6 months. Dyad participants (n = 69) invited an injection,
      sex partner, or family member to the study site to reinforce learnt behavior
      change tools by practicing communication skills and risk reduction lessons. In
      all, 31 participants did not participate in the dyad session. We descriptively
      assessed changes in sharing injection equipment between the 2 time points of pre-
      and postintervention using the tests of proportions by dyad participation.
      Multivariable logistic regression adjusted for sex was used with an interaction
      term (time points * dyad participation) to evaluate the dyad effect. Dyad
      participants reported reduced syringe and cooker sharing at postintervention
      (sharing syringe: 17% versus 39%, P < .05 and cooker: 32% versus 59%, P < .01).
      There was no difference between the dyad group's sharing injection equipment
      behavior after the intervention (sharing syringes: adjusted odds ratio [aOR]
      0.76; 95% confidence interval [CI] 0.1-3.9 and cookers: aOR 0.72; 95% CI 0.1
      3.5). The role of the dyad session alone on risk taking was not effective. With a
      small sample size, it is important to continue to evaluate the nature of peer
      based dyadic experiences in future studies.

PMID- 30210230
TI  - Targeted disruption of the endogenous zebrafish rhodopsin locus as models of
      rapid rod photoreceptor degeneration.
AB  - Purpose: Retinitis pigmentosa (RP) is a collection of genetic disorders that
      results in the degeneration of light-sensitive photoreceptor cells, leading to
      blindness. RP is associated with more than 70 loci that may display dominant or
      recessive modes of inheritance, but mutations in the gene encoding the visual
      pigment rhodopsin (RHO) are the most frequent cause. In an effort to develop
      precise mutations in zebrafish as novel models of photoreceptor degeneration, we
      describe the generation and germline transmission of a series of novel clustered
      regularly interspaced short palindromic repeats (CRISPR)/Cas9-induced insertion
      and deletion (indel) mutations in the major zebrafish rho locus, rh1-1. Methods:
      One- or two-cell staged zebrafish embryos were microinjected with in vitro
      transcribed mRNA encoding Cas9 and a single guide RNA (gRNA). Mutations were
      detected by restriction fragment length polymorphism (RFLP) and DNA sequence
      analyses in injected embryos and offspring. Immunolabeling with rod- and cone
      specific antibodies was used to test for histological and cellular changes.
      Results: Using gRNAs that targeted highly conserved regions of rh1-1, a series of
      dominant and recessive alleles were recovered that resulted in the rapid
      degeneration of rod photoreceptors. No effect on cones was observed. Targeting
      the 5'-coding sequence of rh1-1 led to the recovery of several indels similar to
      disease-associated alleles. A frame shift mutation leading to a premature stop
      codon (T17*) resulted in rod degeneration when brought to homozygosity.
      Immunoblot and fluorescence labeling with a Rho-specific antibody suggest that
      this is indeed a null allele, illustrating that the Rho expression is essential
      for rod survival. Two in-frame mutations were recovered that disrupted the highly
      conserved N-linked glycosylation consensus sequence at N15. Larvae heterozygous
      for either of the alleles demonstrated rapid rod degeneration. Targeting of the
      3'-coding region of rh1-1 resulted in the recovery of an allele encoding a
      premature stop codon (S347*) upstream of the conserved VSPA sorting sequence and
      a second in-frame allele that disrupted the putative phosphorylation site at
      S339. Both alleles resulted in rod death in a dominant inheritance pattern.
      Following the loss of the targeting sequence, immunolabeling for Rho was no
      longer restricted to the rod outer segment, but it was also localized to the
      plasma membrane. Conclusions: The efficiency of CRISPR/Cas9 for gene targeting,
      coupled with the large number of mutations associated with RP, provided a
      backdrop for the rapid isolation of novel alleles in zebrafish that phenocopy
      disease. These novel lines will provide much needed in-vivo models for high
      throughput screens of compounds or genes that protect from photoreceptor
      degeneration.

PMID- 30210234
TI  - Antitumor effects of nadroparin combined with radiotherapy in Lewis lung cancer
      models.
AB  - Background: The beneficial antitumor effects of low-molecular-weight heparins
      (LMWHs) have previously been investigated in basic and clinical studies. In this
      study, the antitumor efficacy of nadroparin combined with radiotherapy was
      investigated in vivo. Methods: A total of 48 tumor-bearing mice were randomly
      divided into six groups (n=8 per group): control group, irradiation group (X),
      LMWH1,000 group, LMWH2,000 group, LMWH1,000+X group and LMWH2,000+X group.
      Following this, tumor growth, weight and inhibitory rate, as well as the survival
      of mice in each group, were determined. Levels of serum interleukin (IL)-6 and
      transforming growth factor (TGF)-beta1 were determined via enzyme-linked
      immunosorbent assay (ELISA) analyses. The expression levels of CD34 were
      investigated using immunohistochemistry analyses to represent the microvascular
      density (MVD) values of tumor tissues. In addition, tumor cell apoptosis was
      investigated using TdT-mediated dUTP nick end labeling (TUNEL) analysis post
      treatment. The expression levels of survivin were analyzed by Western blotting.
      Results: The volumes and weights of tumors in the treatment groups were
      demonstrated to be significantly decreased, which was most obvious in the
      LMWH2,000+X group. The tumor inhibitory rate was significantly increased in the
      treated mice. ELISA assays demonstrated that the concentrations of serum IL-6 and
      TGF-beta1 were significantly decreased in the LMWH2,000+X group. In addition, the
      decreased CD34 expression was found in the combined treatment groups. TUNEL
      assays demonstrated that the apoptosis rate was increased in treated mice, and
      the highest apoptosis rate was exhibited by the LMWH2,000+X group. Results of
      Western blotting demonstrated that combinatory treatment with both nadroparin and
      X-ray irradiation significantly inhibited the expression of survivin. Conclusion:
      These results demonstrated that a combinatory treatment strategy of nadroparin
      with fractionated irradiation had a strong synergistic antitumor effect in vivo,
      which may be associated with the promotion of apoptosis, inhibited secretion of
      TGF-beta1 and IL-6 and down-regulation of CD34 and survivin expression.

PMID- 30210235
TI  - Peripheral blood lymphocyte responses to cytomegalovirus seropositivity after
      allogeneic-hematopoietic stem cell transplantation.
AB  - Background: The main purpose of this study was to investigate the relationship
      among cytomegalovirus (CMV) viremia, peripheral immune cells alternations, and
      leukemia prognosis. Patients and methods: We studied 90 leukemia patients who
      underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) from
      2008 to 2015. Their complete clinical laboratory data were collected until 1 year
      after transplantation. Results: All patients were serum CMV negative before allo
      HSCT. After transplantation, the CMV reactivation group showed increased
      peripheral CD8+ T cells and decreased CD4+ T cells and B cells. However, CD8/CD4
      ratio and B cells restored by control of CMV infection due to 2 months maximum
      course of ganciclovir treatment. CMV seropositivity was positively related to
      leukemia-free survival (LFS) of all recruited leukemia types. Conclusion: In
      summary, CMV drives immune cell post-transplantation fluctuation, which also
      favors LFS of leukemia partly resulted from CD8+ T cells.

PMID- 30210237
TI  - Prognostic value of SOX2, Cyclin D1, P53, and ki-67 in patients with esophageal
      squamous cell carcinoma.
AB  - In this study, we evaluated SOX2, Cyclin D1, p53, and ki-67 expression
      immunohistochemically in 117 samples of surgically resected esophageal squamous
      cell carcinoma (ESCC) and matched normal tumor adjacent tissues and correlated
      the expression with clinicopathological finding and patient survival. Lymph node
      metastasis was observed in 36.8% of patients, and organ metastasis was observed
      in 17.9%. We detected high expression of SOX2, Cyclin D1, p53, and ki-67 in
      46.1%, 70.1%, 54.7%, and 32.5% of ESCC tissues, respectively. SOX2 is localized
      in the tumor cell nuclei, and its expression was significantly associated with N
      stage (p=0.034) and differentiation (p=0.003) and ki-67 expression (p=0.001),
      whereas increased Cyclin D1 expression was correlated with high p53 (p=0.015).
      With regard to survival, we found that ESCC patients with high SOX2 expression
      had significantly better survival time than those with low SOX2 expression
      (p=0.021). A multivariate Cox analysis revealed that therapy and high p53
      expression and venous invasion were independent predictors of unfavorable
      prognosis in overall survival (p=0.039, p=0.004, and p=0.023, respectively).
      Furthermore, higher T stage, clinical stage (pTNM), venous invasion, and high p53
      expression were independent predictors of a worse progression-free survival.
      Notably, co-overexpression of p53 and Cyclin D1 was significantly correlated with
      poor overall survival and progression-free survival (p=0.029 and p=0.0227,
      respectively). Therefore, SOX2 might be considered as a potential prognostic
      indicator and a potential target for therapeutic targets in ESCC. p53 staining
      and combined p53 and Cyclin D1 expression had significantly unfavorable
      prognostic value for patients with ESCC. These findings provide more insight into
      ESCC; thus, further investigations into molecular mechanisms of drug resistance
      are essential.

PMID- 30210236
TI  - Targeting the autophagy in bone marrow stromal cells overcomes resistance to
      vorinostat in chronic lymphocytic leukemia.
AB  - Background: The bone marrow microenvironment constitutes a sanctuary for leukemia
      cells. Recent evidence indicates that environment-mediated drug resistance arises
      from a reciprocal influence between tumor cells and the surrounding stroma. The
      present study aimed to investigate the effect of chronic lymphocytic leukemia
      (CLL) cells on the metabolism of bone marrow stroma, to determine the role of
      this metabolic change in the stroma in vorinostat resistance of CLL cells, and
      thus to assess a novel strategy to target stroma and achieve the maximum
      therapeutic effect of vorinostat. Methods: To evaluate this issue, we used
      freshly isolated CLL cells from peripheral blood samples of patients with CLL,
      and co-cultured them with bone marrow stromal cell lines to examine autophagy
      activity and metabolic changes in both CLL cells and stromal cells after
      vorinostat treatment. Results: The results demonstrated that CLL cells were under
      intrinsic oxidative stress which was further enhanced by vorinostat treatment,
      and released H2O2 outside the cells. The adjacent stromal cells took up H2O2 and
      drove autophagy, mitophagy and glycolysis, resulting in the local production of
      high-energy mitochondrial fuels, which were then taken up by CLL cells to be
      effectively utilized through mitochondrial oxidative phosphorylation to enable
      more ATP production. Notably, targeting autophagic stromal cells with autophagy
      inhibitor remarkably decreased stromal protection against vorinostat treatment in
      CLL cells. Conclusion: This study demonstrated that the stroma in the CLL
      microenvironment is abnormal and undergoes autophagy, and manipulation of
      autophagic stromal cells could serve as a novel promising strategy to circumvent
      stroma-mediated drug resistance in CLL cells.

PMID- 30210238
TI  - Effectiveness of treatment of occipital neuralgia using the nerve block
      technique: a prospective analysis of 44 patients.
AB  - Background: There is a great deal of tools for treatment of occipital neuralgia
      but currently we are lacking a complete consensus among practitioners regarding
      the optimal approach to this debilitating condition. Occipital nerve block (ONB)
      is known as one of the management options but there is lack of scientific
      literature exploring its effectiveness. Materials and methods: The prospective
      study was undertaken between March 2014 and February 2018 at the State Vilnius
      University Hospital. Forty-four patients aged from 28 to 84 years (age mean =
      56.30 +/- 14.71) of which 79.55% were female (n = 35) were diagnosed with
      occipital neuralgia (ON) and treated with a local anaesthetic and corticosteroids
      combination injection into the greater or greater plus lesser occipital nerve (n
      = 29 and n = 15, respectively) and followed up after 6 months. Analysis of the
      outcomes of those patients was done by comparing the Visual Analog Scale (VAS)
      and Barrow Neurological Institute Pain Intensity Score (BNIPIS) prior to
      treatment, 24 hours after the block, and at a follow-up 6 months later. Analgesic
      medication consumption before and after 6 months was recorded. A comparison of
      procedure efficacy in lidocaine and bupivacaine groups was made. Evaluation of
      block potency for acute and chronic pain categories was conducted as well. The
      success criteria were defined as patient satisfaction with own condition for at
      least 6 months, not requiring another block in order to stay comfortable.
      Results: Of 44 patients, 42 (95.45%) who underwent the occipital nerve block
      procedure showed satisfactory results for at least 6 months. Mean headache VAS
      scores decreased from 7.23 +/- 0.93 (pre-treatment) to 1.95 +/- 1.59 (24 hours
      after, p < 0.0001) and increased to 2.21 +/- 1.73 at the follow-up after 6
      months, showing no statistically significant difference between post
      interventional and six-month VAS scores (p = 0.07). In all patients the necessity
      of medication to control pain decreased to 16.67% (n = 7) during the the check-up
      after 6 months. There was no statistically significant difference in the
      effectiveness of ONB with regard to the local anaesthetic used or the pain group
      targeted. Similar results were obtained comparing patients who underwent more
      than one ONB. Conclusions: Occipital nerve block with a local anaesthetic and
      corticosteroids provides a safe, simple, and effective treatment method for the
      patient with medically-refractory occipital neuralgia.

PMID- 30210239
TI  - Placenta percreta complicated by uterine rupture and thrombotic microangiopathy.
AB  - Background: Uterine rupture at the site of a previous caesarean scar with
      abnormal placental penetration through the uterus wall with bladder invasion is a
      rare and serious pregnancy complication. Our aim was to report a case of uterine
      rupture with placenta percreta complicated by thrombotic microangiopathy.
      Materials and methods: We did a literature review and analysed medical
      documentation retrospectively. Results: A patient was admitted with complaints of
      lower abdominal pain at 21 weeks of gestation. Sonography of the caesarean scar
      increased suspicion of placental penetration. Anaemia, thrombocytopenia,
      coagulopathy, and acute kidney injury developed and led to the diagnosis of
      thrombotic microangiopathy. The termination of pregnancy was required due to
      severe deterioration in organ functions. The complete uterine rupture with
      placenta percreta invading the urinary bladder was confirmed, and total
      hysterectomy was performed to control life-threatening haemorrhage. The patient
      was treated by blood component transfusions, renal replacement therapy, and
      plasmapheresis. Good health was confirmed two months later by laboratory and
      instrumental tests. Conclusions: It is a rare but very serious condition that
      increases morbidity of mother and foetus, therefore immediate diagnostics and
      treatment are required.

PMID- 30210240
TI  - Diagnosis, treatment, and outcomes of encapsulated papillary carcinoma: a single
      institution experience.
AB  - Background: Encapsulated papillary carcinoma (EPC) is a rare entity of breast
      cancer accounting for approximately 1-2% of all breast tumours. There are no
      evidence-based guidelines for the treatment of EPC. Materials and methods: From
      the database of the National Centre of Pathology (NCP), we obtained pathology
      reports of 19 patients with histologically confirmed EPC, who were treated at the
      National Cancer Institute (NCI) in Vilnius, Lithuania, between July 2009 and July
      2015. Demographic, diagnostic and treatment data were collected from medical
      records retrospectively. Results: During the indicated period, 19 patients with
      EPC were treated at the NCI. Three of them had pure EPC, they were 74 to 81 years
      of age at the time of diagnosis (mean 76.7 years, median 75 years); all of them
      are still alive and no disease progression has been observed. Seven patients had
      EPC associated with carcinoma in situ. Nine patients had EPC associated with
      invasive breast ductal carcinoma. All patients underwent surgery, in most cases -
      wide local excision. Only one patient died. Conclusions: EPC is a rare form of
      breast cancer and usually presents with an invasive breast carcinoma or carcinoma
      in situ in postmenopausal women. Tumours have an excellent prognosis in the cases
      of pure EPC and in both EPC associated with carcinoma in situ (CIS) and invasive
      carcinoma.

PMID- 30210241
TI  - Hospitalisation of late preterm infants due to lower respiratory tract infections
      in Lithuania, Latvia, and Estonia: incidence, disease severity, and risk factors.
AB  - Background: By two years of age, almost all children experience at least one
      episode of respiratory syncytial virus (RSV) infection, the most common viral
      cause of hospitalisation due to lower respiratory tract infection (LRTI). We
      present data on LRTI hospitalisations (with a special focus on RSV), the course
      of illness, and LRTI hospitalisation risk factors in Lithuania, Latvia, and
      Estonia. Materials and methods: The analysed data were part of a large
      multinational study conducted in 23 countries (PONI). LRTI-related
      hospitalisations were observed during one RSV season for late premature infants
      (born between 33 weeks and 0 days and 35 weeks and 6 days of gestation) <=6
      months of age, who did not receive RSV prophylaxis. The potential risk factors
      and demographics were recorded at study enrolment and at the end of the RSV
      season. The primary endpoint was hospitalisation due to RSV LRTI; the secondary
      endpoints included severity, the course and the outcome of LRTI hospitalisations.
      Results: Out of the 291 infants enrolled in three Baltic states, 19 were
      hospitalised due to LRTI (6.5%). RSV testing was performed for 14 hospitalised
      infants; five infants had a positive test for RSV (1.7%). The majority of the
      hospitalised infants (94.7%) had mild or moderate respiratory illness. Male sex,
      O2 dependency after birth, younger maternal age, and furred pets at home were
      significantly associated with an increased risk for LRTI hospitalisation.
      Conclusions: During one RSV season, the incidence of LRTI hospitalisations among
      late preterm infants was 6.5% and the incidence of RSV LRTI hospitalisations was
      1.7%.

PMID- 30210242
TI  - Evaluation of the presence of MMP-2, TIMP-2, BMP2/4, and TGFbeta3 in the facial
      tissue of children with cleft lip and palate.
AB  - Cleft lip and palate (CLP) is the most common defect affecting the face. The
      treatment consists of surgical reconstruction of the anatomical structures of the
      cleft. Part of the surgical treatment is reconstruction of the alveolar bone by
      means of autogenic bone grafting (osteoplasty). This study aimed to evaluate the
      levels of expression of extracellular matrix remodeling factors in the facial
      tissue of children with a complete unilateral (CU) and a complete bilateral (CB)
      CLP to assess whether the wound healing process is adequate. Twenty-two CLP
      patients were enrolled in this study. Tissue samples were collected during
      alveolar osteoplasty for unilateral (n = 12) or bilateral (n = 10) cleft palate,
      (age range from 6 years 8 months to 12 years 2 months). Control material was
      obtained in the case of tooth extraction (age range from 6 years 9 months to 14
      years 5 months). Immunohistochemistry was used to assess the levels of matrix
      metalloproteinase-2 (MMP-2), tissue inhibitor of metalloproteinase-2 (TIMP-2),
      bone morphogenetic proteins 2 and 4 (BMP2/4), and transforming growth factor
      beta3 (TGFbeta3). Numbers of positively stained cells were graded semi
      quantitatively. Data were analysed using the Kraskel-Wallis rank test and the
      Bonferroni correction. The total number of MMP2-positive cells was significantly
      lower in the CBCLP and in the control group than in the CUCLP (p < 0.001 after
      the Bonferroni correction). The total number of TIMP2-positive cells was
      significantly higher in the CUCLP than in the CBCLP and in the control group (p <
      0.001; p < 0.003 after the Bonferroni correction). The overall number of BMP2/4,
      TGFbeta3-positive cells was significantly higher in the CUCLP than in the CBCLP
      and in the control group (p < 0.001 after the Bonferroni correction). The
      decrease of the relative amount of statistically significant BMP2/4, TGFbeta3,
      MMP-2, TIMP-2 containing bone cells in CBCLP patients identifies affected
      alveolar bone regeneration and remodeling process.

PMID- 30210243
TI  - Congenital cystic adenomatous malformation: a case report and a literature
      review.
AB  - Background: A congenital cystic adenomatoid malformation (CCAM) is a foetal
      pulmonary development abnormality caused by airway dysgenesis that is
      characterized by cystic or adenomatous lesions in the terminal bronchioles. The
      size of the mass, the degree of the mediastinal shift, and the presence of
      hydrops and polyhydramnios can all affect the severity of a case. Treatment can
      be initiated at early stages by applying prenatal and postnatal methods. Because
      CCAM is a rare pathology that is often only accidentally diagnosed during routine
      ultrasounds, we would like to share our case report to enrich the literature on
      this pathology and to present a case successfully treated at our hospital.
      Materials and methods: A patient with her first multiple pregnancy was seen for
      prenatal care and her first ultrasound at 17 weeks of gestation. One of the twins
      was diagnosed with a congenital cystic adenomatoid malformation of the left lung.
      At 20 weeks of gestation, an enlarged left lung with small cysts, a compressed
      right lung, a compressed and displaced heart, and oligohydramnios were observed.
      At 28 weeks of gestation, a fetoplacental circulation disorder appeared. At 32
      weeks of gestation, due the unstable condition of the affected foetus, the twins
      were delivered via a C-section. The treatment of the newborn included
      antibiotics, caffeine citrate, and breathing therapy. Results and conclusions:
      CCAM are often diagnosed by accident when performing routine pregnancy ultrasound
      examinations. CT is the most reliable X-ray-based examination method for
      confirming a diagnosis. When CCAM is suspected in the foetus, amniocentesis and
      cariotype identification are performed, but chromosomal anomalies related to CCAM
      are often not identified. Currently, the best treatment results have been
      achieved by applying combined prenatal therapy and early surgical treatment.

PMID- 30210244
TI  - The impact of music on the bioelectrical oscillations of the brain.
AB  - In this article we conclude the main scientific studies into the changes in the
      bioelectrical brainwave activity that occur while listening to music. A brainwave
      spectral analysis, derived from findings of electroencephalograms, is a powerful
      tool to obtain deep and objective insights into the effects of music on the
      brain. This capacity is being investigated in various contexts. Starting with a
      healthy population, studies also seek to determine the impact of music in such
      conditions as disorders of consciousness, psychiatric diseases, and chronic
      conditions, as well as to further explore the role of music for rehabilitation
      purposes. Supplemental investigations in this field are needed not only to deepen
      the knowledge of general neurophysiology of listening to music, but also to
      possibly open new perspectives for its broader use in clinical practices.

PMID- 30210245
TI  - A survey of some aspects of birthday celebration.
AB  - Background: The tradition of celebrating the day of birth of an individual is
      thought to have existed since the ancient times. Depending on the culture,
      religious beliefs, and the geographic location, occasions for ritual performance
      differ greatly. The aim of this pilot study was to investigate how students in
      Lithuania evaluate the importance of their birthday. Materials and methods: An
      "Invitation to Remember Your Birthday" questionnaire was created by the authors
      to collect the responses for evaluation. The questionnaire consisted of 15
      questions divided into four parts. It assessed how and what the respondents felt
      on their annual birthday, about the organization of the celebration, gift
      receiving, and the value of the ritual. Results: A total of 309 medical students
      of Vilnius University completed the survey (n = 146 year 4, n = 163 year 5). The
      results suggested that the birthday is an important individual occasion, which
      students tend to celebrate annually. The respondents tend to feel better and more
      loved on the day of their birthday. Conclusions: Birthday is seen as an
      opportunity to spend time with friends and family, have a break from daily
      responsibilities, and receive attention from people around them. Birthday
      celebration of medical students is affected by their social and cultural context.
      The findings of this study may be relevant for future studies when searching for
      age- and culture-appropriate ways to use birthday celebration as possible means
      of improving mental health. The current data can be used for longitudinal and
      cross-cultural comparisons.

PMID- 30210246
TI  - The impact of anti-cyclic citrullinated peptide antibody status on the management
      of patients with early rheumatoid arthritis: observational study results from
      Lithuania.
AB  - Background: To provide data on the use of anti-cyclic citrullinated peptide
      antibody (anti-CCP) and other routinely used clinical parameters and to assess
      the impact of anti-CCP status on therapeutic decisions, an observational study
      was conducted in patients with rheumatoid arthritis (RA). Methods: Sixty-seven
      adult patients with a recent diagnosis of RA were recruited from four
      rheumatology centres in Lithuania and were prospectively observed for 12 months.
      Data collection was based on the review of medical records and routine
      examination of patients. Patients completed the Health Assessment Questionnaire -
      Disability Index and Patient Global Assessment of disease activity using a visual
      analogue scale. Physicians were asked about the importance of the anti-CCP
      results and other factors important for therapeutic decisions. Results: Of the 67
      patients enrolled, 54 (80.6%) completed the study. At the beginning of the study,
      physicians considered anti-CCP results to be important for decision-making in
      87.0% of patients. The perceived importance of anti-CCP results did not change
      significantly throughout the study. After one year of treatment, factors that
      were considered more important than the anti-CCP results included the presence of
      erosions, significantly increased C-reactive protein, duration of morning
      stiffness, multi-articular expanding, and rheumatoid factor status. For nearly
      half of the patients (n = 26; 48.1%), physicians would not change the treatment
      strategy if the patient had the opposite anti-CCP results at baseline.
      Conclusions: The study revealed that decision-making in the management of RA was
      based on multifactorial data. The role of anti-CCP as a single test in treatment
      decisions needs further investigation.

PMID- 30210247
TI  - INTER- AND INTRA-OBSERVER AGREEMENT IN THE MILCH AND WEISS SYSTEMS.
AB  - Objective: The aim of this study is to estimate the inter- and intra-observer
      agreement of the Weiss and Milch classification systems in radiological studies
      of fractures of the lateral humeral condyle in pediatric patients. Methods: An
      agreement study was performed with non-probability sampling of consecutive cases
      with a sample size of a hundred radiological studies, which were evaluated by
      three experienced orthopedic surgeons and three resident physicians; following a
      thorough comparison of both inter- and intra-observer agreements over a six-week
      period based on the Fleiss' kappa, which was used to determine the inter- and
      intra-observer agreement rates of both classifications. Results: The overall
      reliability of the entire group of evaluators for the Milch classification in the
      inter-observer evaluation was kappa = 0.13, 95% CI, 0.08-0.18, and the intra
      observer evaluation was kappa = 0.08, 95% CI, 0.06-0.11. For the Weiss
      classification, the overall evaluation had an inter-observer agreement of kappa =
      0.53, 95% CI, 0.50-0.57, and an intra-observer agreement of kappa = 0.22, 95% CI,
      0.20 -0.24. Conclusion: In the present study, the Weiss classification system
      demonstrated greater agreement than the Milch classification; however, the latter
      may require complementary studies, such as an arthrography to enhance
      classification accuracy. Level of Evidence II, Diagnostic Studies - Investigating
      Diagnostic Examination.

PMID- 30210248
TI  - TRANSFER OF NERVE BRANCHES OF THE FLEXOR CARPI RADIALIS TO THE POSTERIOR
      INTEROSSEOUS NERVE.
AB  - Objective: The objective of this paper was to study the anatomical variations of
      the flexor carpi radialis muscle (FCR) and determine in cadaver limbs whether the
      FCR nervous branch can be connected to the posterior interosseous nerve (PIN)
      without tension and how close to the target muscles the transfer can be
      performed. Method: Thirty cadaveric upper limbs were dissected. Results: The FCR
      received exclusive innervation of the median nerve, distally to the intercondylar
      line of the humerus. In 5 limbs, an isolated branch was found and in 25, a common
      trunk with other nervous branches occurred. We investigated whether the branch
      for the FCR was long enough to be transferred to the PIN. The diameter of the
      nerve branch for the FCR corresponded on average to 50% of the PIN. Conclusion:
      In 12 limbs, the branch destined to the FCR could be connected to the PIN,
      distally to the nerve branches to the supinator muscle even during the movements
      of the forearm and the elbow. In 18 specimens, it was necessary to mobilize the
      PIN for this innervation. Level of Evidence IV, Case Series.

PMID- 30210249
TI  - NECROSIS OF THE FEMORAL HEAD AND HEALTH-RELATED QUALITY OF LIFE OF CHILDREN AND
      ADOLESCENTS.
AB  - Objective: To verify the impact of avascular necrosis of the femoral head on the
      quality of life of children and adolescents with Perthes disease and sickle cell
      disease. Methods: A comparative study including 24 children between eight and 18
      years old with avascular necrosis of the femoral head secondary to Perthes
      disease and sickle cell disease (Group with Necrosis) and 24 children considered
      asymptomatic (Group without Necrosis). Clinical and sociodemographic data were
      collected and the PedsQL 4.0 and the Charnley score for hip dysfunction were
      applied. Results: There was no difference in the overall score and in any domain
      when comparing the Perthes group (global = 73.1) and the sickle cell disease
      group (global = 65.9). When comparing the groups with necrosis and without
      necrosis, the Perthes group had a lower overall score only for the Physical
      Functioning domain (87.5 versus 68.5); sickle cell disease group had a lower
      overall score (64.9 versus 79.4) and in the Physical Functioning (68.5 versus
      87.5) and School Functioning (62.9 versus 73.7) domains. Conclusion: Avascular
      necrosis of the femoral head produces lower quality of life scores both in the
      global evaluation and in the domains Physical Functioning and School Functioning.
      Necrosis, bilateral lesion, and hip function were found to be associated with the
      loss of quality of life. Level of Evidence III, Sectional comparative study.

PMID- 30210251
TI  - ASSOCIATION OF TOBACCO DEPENDENCE, ALCOHOLISM AND ANABOLIC STEROIDS WITH
      MENISCOLIGAMENTOUS INJURIES.
AB  - Objective: To determine a relationship between smoking, alcohol abuse and
      anabolic steroids and meniscoligamentous injuries. Methods: A total of 239
      patients underwent surgical treatment of isolated anterior cruciate ligament
      (ACL) lesion, ACL associated with meniscal injury and isolated meniscal injury,
      and were inquired by a single team of surgeons about their habits: smoking,
      alcoholism and use of artificial anabolic agents. In addition, quality of life
      was assessed using the SF-36 questionnaire. Results: It was not possible to
      establish a direct relationship between habits and meniscal and ligamentous
      injuries, despite the finding that patients with ACL-associated lesions were more
      frequently smokers, and that patients with isolated meniscal injuries used more
      artificial anabolic agents. Regarding quality of life, there were no statistical
      differences in the habits between the groups; however, except for smokers with
      isolated meniscal injury, all patients who did not have the habits analyzed
      presented a better score in the SF-36 questionnaire. Conclusion: There were no
      significant findings correlating smoking, alcohol abuse and artificial anabolic
      agents with the presence of injuries. In addition, six months after the surgical
      treatment, there was no difference in the quality of life between the groups
      evaluated. Level of Evidence III, Prospective case series.

PMID- 30210250
TI  - PRELIMINARY MECHANICAL TEST OF PROXIMAL FEMUR REINFORCEMENT WITH CEMENTED X
      SHAPED PMMA.
AB  - Objective: To evaluate the mechanical behavior of the proximal end of the femur
      submitted to the X-shaped polymethylmethacrylate (PMMA) reinforcement technique.
      Methods: Fifteen synthetic femurs, with a Nacional(r) density of 10 PCF, were
      divided into two groups: the DX group, with 5 units that were submitted to PMMA
      reinforcement, and the DP group, with 10 units, which were evaluated intact. The
      volume of PMMA required, the maximum load, and the absorbed energy to fracture
      were analyzed by means of a static mechanical bending test simulating a fall on
      the greater trochanter. Results: A mean of 6 ml of PMMA was used to model the X
      reinforcement; it was observed that the DX group presented significantly higher
      maximum load (median = 1553 N, p = 0.005) and absorbed energy to fracture (median
      = 9.7 J; p = 0.050) than the DP group (median = 905 N and 6.6 J). Conclusion: X
      reinforcement of the proximal end of synthetic femurs showed a statistically
      significant increase in the maximum load and absorbed energy to fracture in the
      mechanical assay when compared to the control group. Level of Evidence III,
      Experimental study.

PMID- 30210252
TI  - CORRELATION BETWEEN AHLBACK CLASSIFICATION AND GONARTHROSIS RISK FACTORS.
AB  - Objective: To demonstrate whether or not there is a correlation between the risk
      factors for gonarthrosis and the radiographic classification of Ahlback. Methods:
      We studied patients with primary gonarthrosis attended at the knee outpatient
      clinic of the General Hospital of Vila Penteado during their routine visit. We
      collected data on patient age (years), weight (kg), height (meters), body mass
      index (BMI = patient weight/height2), personal history of hypertension or
      diabetes mellitus (positive or negative), sedentarism (physical activity less
      than three times per week, 30 minutes per session), functional demand (how many
      blocks walked weekly), time of onset of symptoms (in years) and laterality or
      bilaterality. The data were correlated with the Ahlback classification applied to
      the radiographs performed at the time of the consultation. Results: A sample of
      108 patients was studied. We did not find an association between the Ahlback
      classification and the patient's age, smoking, sedentary lifestyle, laterality,
      number of blocks walked per week, diabetes mellitus, and sex; however, a positive
      association was observed in hypertensive patients as well as a weak correlation
      with height and weight of the patient and moderate correlation with BMI.
      Conclusion: The Ahlback classification is unrelated to most of the risk factors
      for primary gonarthrosis. Level of evidence III, Case-control study.

PMID- 30210253
TI  - EXTRA-ABDOMINAL DESMOID TUMOR: ANALYSIS OF 23 CONSECUTIVE CASES IN A SINGLE
      INSTITUTION.
AB  - Objective: Extra-abdominal desmoid tumor (EDT) is a rare condition, caused by
      proliferation of fibroblasts. Despite being a benign tumor, it is locally
      aggressive and has unpredictable clinical behavior. The objective of this study
      is to present the clinical outcomes of patients with EDT treated surgically
      between 1995 and 2016. Methods: This is a retrospective series of 23 patients
      with histopathological diagnosis of EDT that underwent surgery at the orthopedic
      oncology service of our hospital. The information was obtained from the
      institute's clinical and pathology reports. Results: A total of 223 medical
      records with histopathological reports were evaluated. Only 23 cases of EDT were
      included in the present study. The mean age was 22.5 years. Twelve (52.2%)
      patients had the tumor on the lower limbs, seven (30.4%) on the upper limbs and
      four (17.4%) cases were reported on the back. Five (21.7%) patients had tumors
      measuring less than 5 cm, while eighteen (78.3%) patients had tumors measuring
      more than 5 cm. All patients underwent surgery as the definitive treatment in our
      institute. Twelve (52.2%) cases presented negative margins (NM) and eleven
      (47.8%) cases had positive margins (PM). Local recurrence (LR) occurred in eleven
      (47.8%) patients. Conclusion: Impairment of the surgical margin was the only
      prognostic factor found for LR of EDT. Level of Evidence IV, Case Series.

PMID- 30210254
TI  - EVALUATION OF QUALITY OF LIFE IN PATIENTS TREATED FOR METASTATIC DISEASE OF THE
      PROXIMAL FEMUR.
AB  - Objective: Patients with metastatic bone lesions have a limited life expectancy.
      These metastatic lesions compromise the proximal femur, and fractures are quite
      common. The survival of these patients depends on the behavior of the primary
      tumor. The aim of this study was to evaluate the quality of life of patients with
      extensive metastatic lesion of the proximal femur with pathological or imminent
      fracture, treated with non-conventional endoprosthesis. Methods: From May 2008 to
      August 2012, twenty-five (25) patients with bone metastases of the proximal
      femur, with pathological or imminent fracture were recruited into this study.
      These patients had survived for at least six weeks after surgery and the TESS
      questionnaire (Toronto Extremity Salvage Score) was administered. Results: The
      final score of the TESS was an average of 57 points (SD 23.78 points). There was
      no significant difference in TESS values considering: sex, presence of fracture,
      or site of the bone lesion. Conclusion: The TESS questionnaire provides
      information about the function and quality of life of patients with malignant
      tumors of the lower limbs, from the patient's perspective. The results can be
      considered positive, when compared to the limited life expectancy and complexity
      of this group of patients. Level of evidence III, Therapeutic studies,
      retrospective comparative study.

PMID- 30210255
TI  - TIBIAL ADAMANTINOMA: ANALYSIS OF SEVEN CONSECUTIVE CASES IN A SINGLE INSTITUTION.
AB  - Objective: Adamantinoma accounts for less than 1% of the primary bone neoplasms.
      The tibia is the most affected bone and it is predominant in male patients
      between the second and third decades of life. The objective of this study is to
      obtain epidemiological and clinical information on patients with adamantinoma of
      the tibia treated surgically between 1989 and 2016. Methods: Retrospective series
      of seven patients diagnosed with adamantinoma of the tibia that underwent surgery
      at the orthopedic oncology service of our hospital. The information was obtained
      from the medical records and histopathological reports of our institution.
      Results: A total of 2870 medical records with histological reports were
      evaluated. Seven cases of adamantinoma of the tibia were included. The mean age
      was 28.5 (17-49) years. We found a predominance of females (71.4%) and the most
      affected side was the left one, with four cases (57.1%). The biopsy revealed bone
      adamantinoma in four (57.1%) patients, while the diagnosis of the other patients
      was confirmed after the histological examination of the surgical specimen. All
      the patients underwent surgery as definitive treatment. No positive margins were
      reported. No local recurrence (LR) was reported and two patients had distant
      metastasis (DM). Conclusion: The prognosis of survival in cases of adamantinoma
      of the tibia is high. The rates of LR and DM were low. Surgical treatment with
      extensive tumor resection is the treatment of choice. Level of Evidence IV, Case
      Series.

PMID- 30210256
TI  - EXPLORING CORTICAL BONE DENSITY THROUGH THE ULTRASOUND INTEGRATED REFLECTION
      COEFFICIENT.
AB  - Objective: This work evaluates the relationship between ultrasonic reflection and
      bone density from fourteen cylindrical bovine cortical bone samples (3.0-cm
      thick). Methods: Twenty US reflection signals per sample were acquired along the
      bone surface (2.0-mm step). The Integrated Reflection Coefficient (IRC) from each
      signal was compared to Quantitative Computed Tomography (QCT). Results: Seven IRC
      and QCT curves presented Pearson's Correlation R-values above 0.5. For weak
      correlation curves, QCT and IRC showed similar trends in several segments.
      Conclusion: IRC was sensitive to bone density variation. Level of Evidence:
      Experimental Study, Investigating a Diagnostic Test.

PMID- 30210257
TI  - SACRECTOMY ASSOCIATED WITH VERTEBRECTOMY: A NEW TECHNIQUE USING DOWEL GRAFTS FROM
      CADAVERS.
AB  - Objective: The purpose of this study was to demonstrate, in a case series, a new
      sacrectomy technique using an iliac crest dowel graft from a cadaver. Study
      design: Report of a case series with description of a new surgical technique.
      Methods: The technique uses four bars to support the posterior spine and a dowel
      graft in the iliac wings, with compression of the spine and pelvis above it, to
      support the anterior spine. Three cases were operated on, and in all of them, a
      vertebrectomy was used. Results: In the first two cases, the technique was
      performed as a two-stage surgery. The first stage was performed via the anterior
      and peritoneal access routes, and the second stage via the posterior access
      route. In the third case, retroperitoneal access via the anterior route meant
      that the technique could be performed in one stage, resulting in an overall
      reduction in surgical time (1250 vs. 1750 vs. 990 minutes, respectively).
      Conclusion: The new technique enables fixation with biomechanical stability,
      which is essential to support the stress in the lumbosacral transition and
      promote earlier rehabilitation. Level of evidence IV, case series.

PMID- 30210259
TI  - PHYSICAL ACTIVITY PROGRAM FOR ELDERLY AND ECONOMY FOR THE HEALTH SYSTEM.
AB  - Objective: To evaluate the impact of physical activity on the use of the health
      system and the quality of life in sedentary elderly. Methods: A prospective
      interventional study was carried out between March 2010 and February 2011 with
      100 subjects (60-90 years of age,) divided into active group (AG) and control
      group (CG). During this period, AG performed physical exercise twice a week in 60
      minute sessions and the CG remained sedentary with observation of their
      activities. Before and after the study, all subjects were clinically evaluated
      and completed a quality of life questionnaire. Results: Eighty-nine subjects (AG
      = 44; CG = 45) were analyzed. AG had fewer visits to emergency room (p = 0.0056),
      hospitalizations (p = 0.0011), length of hospital stay (p = 0.0012) and fewer
      subsidiary tests (p = 0.0236) compared to the CG. The quality of life score
      analyzed before and after physical activity increased in AG compared to CG (p <
      0.0001) and among subjects in AG (p < 0.0001), with no change in the CG.
      Conclusion: The intervention of a physical activity program for sedentary elderly
      can contribute to reduce the use of the health system and improve the quality of
      life. Level of evidence II, Therapeutics Studies. Prospective comparative study.

PMID- 30210258
TI  - BIOMECHANICAL COMPARISON OF MEDIAL VERSUS LATERAL SIDED PLATING IN FEMORAL
      FRACTURES.
AB  - Objective: The aim of the present study was to determine whether the side of
      application of the plate itself affects the mechanical stability of the fixation.
      The specific question addressed is whether or not a lateral or medial plate
      application is biomechanically better, for the treatment of distal diaphysis
      fractures of the femur. Methods: Stability and stiffness of medial sided plating
      relative to the conventional lateral sided plating in distal diaphysis of the
      femur were measured by analyzing axial loading forces leading to implant failure.
      Sixty synthetic femurs were tested in physiological bending, to calculate the
      yield and ultimate load to displacement following fixation of distal diaphysis
      fractures of the femur by either medial or lateral sided plating. Axial loading
      was applied to samples using a uniaxial testing machine. Results: There was more
      implant deformation in the lateral sided plating group - a difference with
      statistical significance. Conclusion: Medial sided plating was found to be as
      stiff as lateral plating. Medial plating may be a reasonable treatment option
      that can be used safely in selected cases. Level of Evidence I, Therapeutic
      Studies Investigating the Results of Treatment.

PMID- 30210260
TI  - RELATION BETWEEN IMPACT FACTOR IN ORTHOPEDIC JOURNALS AND LEVEL OF EVIDENCE.
AB  - Objective: This study aims to assess the quality of articles published in the
      leading orthopedic surgery journals, by measuring the relation between the impact
      factor and the number studies with a high level of evidence. Methods: A
      literature review was performed of articles published in four previously selected
      journals. A score of journal evidence (RER - Relation between Randomized clinical
      trials and Systematic reviews) was calculated, considering the number of RCTs and
      SR published and the total number of full-text articles. Results: The selected
      journals were JBJS-Am, ASMJ, BJJ-Br and Arthroscopy, with Impact factors of
      5.280, 4.362, 3.309 and 3.206 respectively in 2015. In the study, the RER Scores,
      in the same order, were 9.408, 6.153, 7.456 and 7.779. Conclusion: The journal
      JBJS-Am is the best available source of information on orthopedic surgery from
      this point of view. It has the highest Impact Factor and clearly the highest RER
      Score. On the other hand, we could conclude that the number of published RCT and
      good quality SR is very low, with less than 10% of all the articles. Level of
      evidence III, Analyses based on limited alternatives and costs, and poor
      estimates.

PMID- 30210261
TI  - Framing drug and alcohol use as a public health problem in Britain: past and
      present.

PMID- 30210263
TI  - Response to: Comment on "Gut Microbiota as a Driver of Inflammation in
      Nonalcoholic Fatty Liver Disease".

PMID- 30210262
TI  - Lactobacillus reuteri LR1 Improved Expression of Genes of Tight Junction Proteins
      via the MLCK Pathway in IPEC-1 Cells during Infection with Enterotoxigenic
      Escherichia coli K88.
AB  - Intestinal epithelial barrier damage disrupts immune homeostasis and leads to
      many intestinal disorders. Lactobacillus reuteri strains have probiotic functions
      in their modulation of the microbiota and immune system in intestines. In this
      study, the effects of L. reuteri LR1, a new strain isolated from the feces of
      weaning piglets, on intestinal epithelial barrier damage in IPEC-1 cells caused
      by challenge with enterotoxigenic Escherichia coli (ETEC) K88 were examined. It
      was found that L. reuteri LR1, in large part, offset the ETEC K88-induced
      increase in permeability of IPEC-1 cell monolayers and decreased the adhesion and
      invasion of the coliform in IPEC-1 cells. In addition, L. reuteri LR1 increased
      transcript abundance and protein contents of tight junction (TJ) proteins zonula
      occluden-1 (ZO-1) and occludin in ETEC K88-infected IPEC-1 cells, whereas it had
      no effects on claudin-1 and F-actin expression. Using colloidal gold
      immunoelectron microscopy, these effects of L. reuteri LR1 on ZO-1 and occludin
      content in IPEC-1 cells were confirmed. By using ML-7, a selective inhibitor of
      myosin light-chain kinase (MLCK), the beneficial effect of L. reuteri LR1 on
      contents of ZO-1 and occludin was shown to be dependent on the MLCK pathway. In
      conclusion, L. reuteri LR1 had beneficial effects on epithelial barrier function
      consistent with increasing ZO-1 and occludin expression via a MLCK-dependent
      manner in IPEC-1 cells during challenge with ETEC K88.

PMID- 30210264
TI  - Comparative Genomic Analysis of Members of the Genera Methanosphaera and
      Methanobrevibacter Reveals Distinct Clades with Specific Potential Metabolic
      Functions.
AB  - Methanobrevibacter and Methanosphaera species represent some of the most
      prevalent methanogenic archaea in the gastrointestinal tract of animals and
      humans and play an important role in this environment. The aim of this study was
      to identify genomic features that are shared or specific for members of each
      genus with a special emphasis of the analysis on the assimilation of nitrogen and
      acetate and the utilization of methanol and ethanol for methanogenesis. Here,
      draft genome sequences of Methanobrevibacter thaueri strain DSM 11995T,
      Methanobrevibacter woesei strain DSM 11979T, and Methanosphaera cuniculi strain
      4103T are reported and compared to those of 16 other Methanobrevibacter and
      Methanosphaera genomes, including genomes of the 13 currently available types of
      strains of the two genera. The comparative genome analyses indicate that among
      other genes, the absence of molybdopterin cofactor biosynthesis is conserved in
      Methanosphaera species but reveals also that the three species share a core set
      of more than 300 genes that distinguishes the genus Methanosphaera from the genus
      Methanobrevibacter. Multilocus sequence analysis shows that the genus
      Methanobrevibacter can be subdivided into clades, potentially new genera, which
      may display characteristic specific metabolic features. These features include
      not only the potential ability of nitrogen fixation and acetate assimilation in a
      clade comprised of Methanobrevibacter species from the termite gut and
      Methanobrevibacter arboriphilus strains but also the potential capability to
      utilize ethanol and methanol in a clade comprising Methanobrevibacter wolinii
      strain DSM 11976T, Mbb. sp. AbM4, and Mbb. boviskoreani strain DSM 25824T.

PMID- 30210267
TI  - Effect of Temperature Cycling on Ostwald Ripening.
AB  - We study the effect of temperature cycling on the rate of Ostwald ripening (or
      coarsening) of spherical particles dispersed in a binary solution. A widespread
      view, which states a temperature cycle generally enhances the rate of Ostwald
      ripening by first dissolving the smallest particles (heating) and then regrowing
      the dissolved amount of material on the remaining particles (cooling), is shown
      to be inadequate as it does not include transient effects. On the basis of a
      simulation method that assumes mass transfer as the limiting growth mechanism, we
      show that each temperature cycle is followed by a significant relaxation of the
      particle-size distribution, during which the number of particles remains
      constant, and the average particle size decreases. The relaxation is shown to be
      crucial to obtain a linear scaling of the average particle radius cubed with the
      number of cycles applied (or time), which is the behavior generally observed for
      the evolution of ice crystals in cycling experiments on frozen aqueous solutions
      or frozen foods. We show the experimentally observed increase in the
      proportionality constant (or "coarsening rate") as compared to isothermal
      ripening, or the increase of the coarsening rate with increasing cycle frequency,
      can be reproduced convincingly only if some (transient) ripening is allowed to
      take place at the elevated temperature of each cycle. Our results thus suggest
      the effect of temperature cycling on Ostwald ripening is governed by a
      dissolution-ripening-regrowth-relaxation mechanism.

PMID- 30210265
TI  - Revision of Eocene electric rays (Torpediniformes, Batomorphii) from the Bolca
      Konservat-Lagerstatte, Italy, reveals the first fossil embryo in situ in marine
      batoids and provides new insights into the origin of trophic novelties in coral
      reef fishes.
AB  - The Eocene electric ray ?Titanonarke Carvalho, 2010 from the Bolca Konservat
      Lagerstatte, north-eastern Italy, is redescribed in detail based upon new
      material from recent excavations. This taxon exhibits a combination of features
      (large voids between the pectoral and the axial skeleton filled in life by
      electric organs, anteriorly directed fan-shaped antorbital cartilages, lack of
      dermal denticles, long prepelvic processes, and rounded basibranchial copula with
      a small caudal tab) that clearly supports its assignment to the order
      Torpediniformes. The analysis of new material also demonstrates that the previous
      apparent absence of typical narcinoid characters used to diagnose ?Titanonarke
      was the result of taphonomic biases. ?Titanonarke shares at least three
      synapomorphies (presence of a rostral fontanelle, low number of ribs, and rostral
      cartilage connected to the antorbital cartilage through lateral appendices) with
      the extant genera Benthobatis, Diplobatis, Discopyge and Narcine, with which it
      forms a clade (family Narcinidae) recognized herein as unquestionably
      monophyletic. Moreover, based upon a single specimen of ?Titanonarke that
      exhibits a unique combination of morphometric and meristic features, a new
      species of Eocene numbfish ?T. megapterygia sp. nov., is recognized. The presence
      of several specimens representing different ontogenetic stages of at least two
      species of numbfishes suggests a close association of this taxon with shallow
      water habitats corresponding to coral reefs as hypothesized for the Monte Postale
      palaeoenvironment. The occurrence of a fossilized marine batoid embryo is
      reported here for the first time. Moreover, the analysis of the gut contents
      suggests that the dietary adaptations of ?Titanonarke can be related, at least in
      part, to an opportunistic strategy in the context of abundant larger foraminifera
      in the Monte Postale palaeobiotope, suggesting that this kind of feeding mode,
      known to occur in present-day reefs, already was realized 50 million years ago.

PMID- 30210266
TI  - Comparison of high-dose Cisplatin-based chemoradiotherapy and Cetuximab-based
      bioradiotherapy for p16-positive oropharyngeal squamous cell carcinoma in the
      context of revised HPV-based staging.
AB  - AIM: To perform a comparison of Cisplatin vs. Cetuximab in p16-positive
      oropharyngeal squamous cell carcinoma (OPSCC) in the context of the revised HPV
      based staging. BACKGROUND: Previous reports comparing these agents in head and
      neck cancer have included heterogenous disease and p16-status. MATERIALS AND
      METHODS: A retrospective review was conducted from 2006 to 2016 of patients with
      p16-positive OPSCC who underwent definitive radiotherapy concurrent with either
      triweekly Cisplatin (n = 251) or Cetuximab (n = 40). AJCC 8th Edition staging was
      adapted. RESULTS: Median follow-up for surviving patients was 40 months. On
      multivariate analysis for all-comers, comparing Cisplatin and Cetuximab, 3-year
      locoregional recurrence (LRR): 6% vs. 16% (p = 0.07), 3-year distant metastasis
      (DM): 8% vs. 21% (p = 0.04), 3-year overall recurrence rate (ORR): 11% vs. 29% (p
      = 0.01), and 3-year cause-specific survival (CSS): 94% vs. 79% (p = 0.06),
      respectively. On stage-based subgroup analysis, for stage I-II disease, 3-year
      LRR: 5% vs. 10% (p = 0.51), 3-year DM: 7% vs. 16% (p = 0.32), 3-year ORR: 10% vs.
      23% (p = 0.15), and 3-year CSS: 95% vs. 82% (p = 0.38). For stage III disease, 3
      year LRR: 10% vs. 40% (p = 0.07), 3-year DM: 9% vs. 43% (p = 0.07), 3-year ORR:
      15% vs. 55% (p = 0.04), and 3-year CSS: 94% vs. 57% (p = 0.048). CONCLUSIONS:
      When given concurrently with radiotherapy, Cetuximab and triweekly Cisplatin
      demonstrated comparable efficacy for AJCC 8th Edition stage I-II p16-positive
      OPSCC. However, Cetuximab appeared to be associated with higher rates of
      treatment failure and cancer-related deaths in stage III disease. Upon
      availability of the RTOG 1016 trial results, analysis based on the revised HPV
      based staging should be performed to confirm these findings.

PMID- 30210268
TI  - Optimal LDR to Protect the Kidney From Diabetes: Whole-Body Exposure to 25 mGy X
      rays Weekly for 8 Weeks Efficiently Attenuates Renal Damage in Diabetic Mice.
AB  - To explore an optimal frequency of whole-body low-dose radiation (LDR) to protect
      the kidney from diabetes, type 1 diabetic mice were induced with multiple
      injections of low-dose streptozotocin in male C57BL/6J mice. Diabetic or age
      matched normal mice received whole-body exposure to 12.5 or 25 mGy either every
      other day or weekly for 4 or 8 weeks. Diabetes decreased the urinary creatinine
      and increased the microalbumin in urine, renal accumulation of 3-nitrotyrosine
      and 4-hydroxynonenal, and renal expression of collagen IV and fibronectin. All
      these renal pathological and functional changes in diabetic mice were
      significantly attenuated by exposure to LDR at all regimens. However, whole-body
      exposure of diabetic mice to 25 mGy weekly and to 12.5 mGy every other day for 8
      weeks provided a better prevention of diabetic nephropathy than other LDR
      regimens. Furthermore, whole-body exposure to 25 mGy weekly for 8 weeks showed no
      detectable effect on the kidney of normal mice, but whole-body exposure to normal
      mice at 12.5 mGy every other day for 8 weeks increased urinary microalbumin and
      renal expression of collagen IV and fibronectin. These results suggest that whole
      body exposure to LDR at 25 mGy weekly is the optimal condition of LDR to protect
      the kidney from diabetes.

PMID- 30210269
TI  - Hormetic Effects of Early Juvenile Radiation Exposure on Adult Reproduction and
      Offspring Performance in the Cricket (Acheta domesticus).
AB  - Exposure to low-dose ionizing radiation can have positive impacts on biological
      performance-a concept known as hormesis. Although radiation hormesis is well
      documented, the predominant focus has been medical. In comparison, little
      research has examined potential effects of early life radiation stress on
      organismal investment in life history traits that closely influence evolutionary
      fitness (eg, patterns of growth, survival, and reproduction). Evaluating the
      fitness consequences of radiation stress is important, given that low-level
      radiation pollution from anthropogenic sources is considered a major threat to
      natural ecosystems. Using the cricket (Acheta domesticus), we tested a wide range
      of doses to assess whether a single juvenile exposure to radiation could induce
      hormetic benefits on lifetime fitness measures. Consistent with hormesis, we
      found that low-dose juvenile radiation positively impacted female fecundity,
      offspring size, and offspring performance. Remarkably, even a single low dose of
      radiation in early juvenile development can elicit a range of positive fitness
      effects emerging over the life span and even into the next generation.

PMID- 30210270
TI  - Resurrection of Cortinarius coalescens: taxonomy, chemistry, and ecology.
AB  - Cortinarius coalescens Karcher & Seibt is a rare European species of the subgenus
      Phlegmacium, section Phlegmacioides, neglected in recent molecular studies. New
      primers (CortF and CortR) designed for species in the section Phlegmacioides
      allowed to obtain ITS rDNA sequence data from the holotype collection of C.
      coalescens; according to the results, this epithet has priority over C. crassorum
      Rob. Henry ex Rob. Henry, C. pardinus Reumaux, and C. parargutus Bidaud, Moenne
      Locc. & Reumaux. Morphological and ecological observations on recent collections
      of C. coalescens from the Czech Republic in comparison with the co-occurring C.
      largus are discussed. Nomenclatural and taxonomic comments on C. tomentosus Rob.
      Henry, C. balteatotomentosus Rob. Henry, and C. subtomentosus Reumaux are also
      provided. So far, C. coalescens is known with certainty from Germany, France, and
      the Czech Republic, where it grows in deciduous forests on acid to neutral soils.
      Arsenic and its compounds were determined in C. coalescens and related species of
      the section Phlegmacioides: C. largus, C. pseudodaulnoyae, and C. variecolor.
      Total arsenic concentrations were in the range 3.6-30.2 mg kg-1 (dry matter) and
      arsenobetaine was the major arsenic compound.

PMID- 30210271
TI  - Intravenously Injected Amyloid-beta Peptide With Isomerized Asp7 and
      Phosphorylated Ser8 Residues Inhibits Cerebral beta-Amyloidosis in AbetaPP/PS1
      Transgenic Mice Model of Alzheimer's Disease.
AB  - Cerebral beta-amyloidosis, an accumulation in the patient's brain of aggregated
      amyloid-beta (Abeta) peptides abnormally saturated by divalent biometal ions, is
      one of the hallmarks of Alzheimer's disease (AD). Earlier, we found that
      exogenously administrated synthetic Abeta with isomerized Asp7 (isoD7-Abeta)
      induces Abeta fibrillar aggregation in the transgenic mice model of AD. IsoD7
      Abeta molecules have been implied to act as seeds enforcing endogenous Abeta to
      undergo pathological aggregation through zinc-mediated interactions. On the basis
      of our findings on zinc-induced oligomerization of the metal-binding domain of
      various Abeta species, we hypothesize that upon phosphorylation of Ser8, isoD7
      Abeta loses its ability to form zinc-bound oligomeric seeds. In this work, we
      found that (i) in vitro isoD7-Abeta with phosphorylated Ser8 (isoD7-pS8-Abeta) is
      less prone to spontaneous and zinc-induced aggregation in comparison with isoD7
      Abeta and intact Abeta as shown by thioflavin T fluorimetry and dynamic light
      scattering data, and (ii) intravenous injections of isoD7-pS8-Abeta significantly
      slow down the progression of institutional beta-amyloidosis in AbetaPP/PS1
      transgenic mice as shown by the reduction of the congophilic amyloid plaques'
      number in the hippocampus. The results support the role of the zinc-mediated
      oligomerization of Abeta species in the modulation of cerebral beta-amyloidosis
      and demonstrate that isoD7-pS8-Abeta can serve as a potential molecular tool to
      block the aggregation of endogenous Abeta in AD.

PMID- 30210272
TI  - Rapid Decoding of Hand Gestures in Electrocorticography Using Recurrent Neural
      Networks.
AB  - Brain-computer interface (BCI) is a direct communication pathway between brain
      and external devices, and BCI-based prosthetic devices are promising to provide
      new rehabilitation options for people with motor disabilities.
      Electrocorticography (ECoG) signals contain rich information correlated with
      motor activities, and have great potential in hand gesture decoding. However,
      most existing decoders use long time windows, thus ignore the temporal dynamics
      within the period. In this study, we propose to use recurrent neural networks
      (RNNs) to exploit the temporal information in ECoG signals for robust hand
      gesture decoding. With RNN's high nonlinearity modeling ability, our method can
      effectively capture the temporal information in ECoG time series for robust
      gesture recognition. In the experiments, we decode three hand gestures using ECoG
      signals of two participants, and achieve an accuracy of 90%. Specially, we
      investigate the possibility of recognizing the gestures in a time interval as
      short as possible after motion onsets. Our method rapidly recognizes gestures
      within 0.5 s after motion onsets with an accuracy of about 80%. Experimental
      results also indicate that the temporal dynamics is especially informative for
      effective and rapid decoding of hand gestures.

PMID- 30210273
TI  - Inhibitive Effects of FGF2/FGFR1 Pathway on Astrocyte-Mediated Inflammation in
      vivo and in vitro After Infrasound Exposure.
AB  - Infrasound, a kind of ambient noise, can cause severe disorders to various human
      organs, specially to central nervous system (CNS). Our previous studies have
      shown that infrasound-induced CNS injury was closely related with astrocytes
      activation and astrocytes-mediated neuroinflammation, but the underlying
      molecular mechanisms are still largely unclear. FGF2/FGFR1 (Fibroblast growth
      factor 2/Fibroblast growth factor receptor 1) pathway was reported to play an
      important role in anti-inflammation in CNS disorders. To further study the
      possible roles of FGF2/FGFR1 pathway in infrasound-induced CNS injury, here we
      exposed Sprague-Dawley rats or cultured astrocytes to 16 Hz, 150 dB infrasound,
      and explored the effects of FGF2 on infrasound-induced astrocytes activation and
      neuroinflammation. Western blotting, immunofluorescence and liquid chip method
      were used in this experiment. Our results showed that after 3- or 7-day exposure
      (2 h/day) of rats as well as 2 h exposure of cultured astrocytes to 16 Hz, 150 dB
      infrasound, astrocyte-expressed FGFR1 was downregulated in vivo and in vitro.
      FGF2 pretreatment not only inhibited infrasound-induced astrocyte activation in
      rat hippocampal CA1 region, but also reduced the levels of pro-inflammatory
      cytokines, such as TNF-alpha, IL-1beta, IL-18, IL-6, and IFN-gamma in vitro and
      in vivo. However, FGF2 significantly upregulated the expression of FGFR1.
      Furthermore, we showed that FGF2 could attenuate IkappaBalpha phosphorylation, NF
      kappaB p65 translocation, pro-inflammatory cytokines levels, and neuronal loss in
      the CA1 region induced by infrasound. On the contrary, PD173074, a special
      antagonist of FGFR1, could reverse the effects above in vitro and in vivo. Taken
      together, our findings showed that FGF2/FGFR1 pathway may exert inhibitive
      effects on astrocyte-mediated neuroinflammation in vitro and in vivo after
      infrasound exposure.

PMID- 30210274
TI  - Neural and Synaptic Array Transceiver: A Brain-Inspired Computing Framework for
      Embedded Learning.
AB  - Embedded, continual learning for autonomous and adaptive behavior is a key
      application of neuromorphic hardware. However, neuromorphic implementations of
      embedded learning at large scales that are both flexible and efficient have been
      hindered by a lack of a suitable algorithmic framework. As a result, most
      neuromorphic hardware are trained off-line on large clusters of dedicated
      processors or GPUs and transferred post hoc to the device. We address this by
      introducing the neural and synaptic array transceiver (NSAT), a neuromorphic
      computational framework facilitating flexible and efficient embedded learning by
      matching algorithmic requirements and neural and synaptic dynamics. NSAT supports
      event-driven supervised, unsupervised and reinforcement learning algorithms
      including deep learning. We demonstrate the NSAT in a wide range of tasks,
      including the simulation of Mihalas-Niebur neuron, dynamic neural fields, event
      driven random back-propagation for event-based deep learning, event-based
      contrastive divergence for unsupervised learning, and voltage-based learning
      rules for sequence learning. We anticipate that this contribution will establish
      the foundation for a new generation of devices enabling adaptive mobile systems,
      wearable devices, and robots with data-driven autonomy.

PMID- 30210275
TI  - New Antibody-Free Mass Spectrometry-Based Quantification Reveals That C9ORF72
      Long Protein Isoform Is Reduced in the Frontal Cortex of Hexanucleotide-Repeat
      Expansion Carriers.
AB  - Frontotemporal dementia (FTD) is a fatal neurodegenerative disease characterized
      by behavioral and language disorders. The main genetic cause of FTD is an
      intronic hexanucleotide repeat expansion (G4C2)n in the C9ORF72 gene. A loss of
      function of the C9ORF72 protein associated with the allele-specific reduction of
      C9ORF72 expression is postulated to contribute to the disease pathogenesis. To
      better understand the contribution of the loss of function to the disease
      mechanism, we need to determine precisely the level of reduction in C9ORF72 long
      and short isoforms in brain tissue from patients with C9ORF72 mutations. In this
      study, we developed a sensitive and robust mass spectrometry (MS) method for
      quantifying C9ORF72 isoform levels in human brain tissue without requiring
      antibody or affinity reagent. An optimized workflow based on surfactant-aided
      protein extraction and pellet digestion was established for optimal recovery of
      the two isoforms in brain samples. Signature peptides, common or specific to the
      isoforms, were targeted in brain extracts by multiplex MS through the parallel
      reaction monitoring mode on a Quadrupole-Orbitrap high resolution mass
      spectrometer. The assay was successfully validated and subsequently applied to
      frontal cortex brain samples from a cohort of FTD patients with C9ORF72 mutations
      and neurologically normal controls without mutations. We showed that the C9ORF72
      short isoform in the frontal cortices is below detection threshold in all tested
      individuals and the C9ORF72 long isoform is significantly decreased in C9ORF72
      mutation carriers.

PMID- 30210277
TI  - Targeted Sequencing of Alzheimer Disease Genes in African Americans Implicates
      Novel Risk Variants.
AB  - The genetic architecture of late-onset Alzheimer disease (AD) in African
      Americans (AAs) differs from that in persons of European ancestry. In addition to
      APOE, genome-wide association studies (GWASs) of AD in AA samples have implicated
      ABCA7, COBL, and SLC10A2 as AA-AD risk genes. Previously, we identified by whole
      exome sequencing a small number of AA AD cases and subsequent genotyping in a
      large AA sample of AD cases and controls association of AD risk with a pair of
      rare missense variants in AKAP9. In this study, we performed targeted deep
      sequencing (including both introns and exons) of approximately 100 genes
      previously linked to AD or AD-related traits in an AA cohort of 489 AD cases and
      472 controls to find novel AD risk variants. We observed association with an 11
      base-pair frame-shift loss-of-function (LOF) variant in ABCA7 (rs567222111) for
      which the evidence was bolstered when combined with data from a replication AA
      cohort of 484 cases and 484 controls (OR = 2.42, p = 0.022). We also found
      association of AD with a rare 9 bp deletion (rs371245265) located very close to
      the AKAP9 transcription start site (rs371245265, OR = 10.75, p = 0.0053). The
      most significant findings were obtained with a rare protective variant in F5 (OR
      = 0.053, p = 6.40 * 10-5), a gene that was previously associated with a brain MRI
      measure of hippocampal atrophy, and two common variants in KIAA0196 (OR = 1.51,
      p<8.6 * 10-5). Gene-based tests of aggregated rare variants yielded several
      nominally significant associations with KANSL1, CNN2, and TRIM35. Although no
      associations passed multiple test correction, our study adds to a body of
      literature demonstrating the utility of examining sequence data from multiple
      ethnic populations for discovery of new and impactful risk variants. Larger
      sample sizes will be needed to generate well-powered epidemiological
      investigations of rare variation, and functional studies are essential for
      establishing the pathogenicity of variants identified by sequencing.

PMID- 30210278
TI  - Breaking Liebig's Law: An Advanced Multipurpose Neuromorphic Engine.
AB  - We present a massively-parallel scalable multi-purpose neuromorphic engine. All
      existing neuromorphic hardware systems suffer from Liebig's law (that the
      performance of the system is limited by the component in shortest supply) as they
      have fixed numbers of dedicated neurons and synapses for specific types of
      plasticity. For any application, it is always the availability of one of these
      components that limits the size of the model, leaving the others unused. To
      overcome this problem, our engine adopts a unique novel architecture: an array of
      identical components, each of which can be configured as a leaky-integrate-and
      fire (LIF) neuron, a learning-synapse, or an axon with trainable delay. Spike
      timing dependent plasticity (STDP) and spike timing dependent delay plasticity
      (STDDP) are the two supported learning rules. All the parameters are stored in
      the SRAMs such that runtime reconfiguration is supported. As a proof of concept,
      we have implemented a prototype system with 16 neural engines, each of which
      consists of 32768 (32k) components, yielding half a million components, on an
      entry level FPGA (Altera Cyclone V). We verified the prototype system with
      measurement results. To demonstrate that our neuromorphic engine is a high
      performance and scalable digital design, we implemented it using TSMC 28nm HPC
      technology. Place and route results using Cadence Innovus with a clock frequency
      of 2.5 GHz show that this engine achieves an excellent area efficiency of 1.68
      MUm2 per component: 256k (218) components in a silicon area of 650 MUm * 680 MUm
      (~0.44 mm2, the utilization of the silicon area is 98.7%). The power consumption
      of this engine is 37 mW, yielding a power efficiency of 0.92 pJ per synaptic
      operation (SOP).

PMID- 30210276
TI  - Cardiac Autonomic Neuropathy in Diabetes: A Predictor of Cardiometabolic Events.
AB  - Autonomic nervous system (ANS) imbalance manifesting as cardiac autonomic
      neuropathy in the diabetic population is an important predictor of cardiovascular
      events. Symptoms and signs of ANS dysfunction, such as resting heart rate
      elevations, diminished blood pressure responses to standing, and altered time and
      frequency domain measures of heart rate variability in response to deep
      breathing, standing, and the Valsalva maneuver, should be elicited from all
      patients with diabetes and prediabetes. With the recognition of the presence of
      ANS imbalance or for its prevention, a rigorous regime should be implemented with
      lifestyle modification, physical activity, and cautious use of medications that
      lower blood glucose. Rather than intensifying diabetes control, a regimen
      tailored to the individual risk of autonomic imbalance should be implemented. New
      agents that may improve autonomic function, such as SGLT2 inhibitors, should be
      considered and the use of incretins monitored. One of the central mechanisms of
      dysfunction is disturbance of the hypothalamic cardiac clock, a consequence of
      dopamine deficiency that leads to sympathetic dominance, insulin resistance, and
      features of the metabolic syndrome. An improvement in ANS balance may be critical
      to reducing cardiovascular events, cardiac failure, and early mortality in the
      diabetic population.

PMID- 30210279
TI  - How Metabolic State May Regulate Fear: Presence of Metabolic Receptors in the
      Fear Circuitry.
AB  - Metabolic status impacts on the emotional brain to induce behavior that maintains
      energy balance. While hunger suppresses the fear circuitry to promote explorative
      food-seeking behavior, satiety or obesity may increase fear to prevent
      unnecessary risk-taking. Here we aimed to unravel which metabolic factors, that
      transfer information about the acute and the chronic metabolic status, are of
      primary importance to regulate fear, and to identify their sites of action within
      fear-related brain regions. We performed a de novo analysis of central and
      peripheral metabolic factors that can penetrate the blood-brain barrier using
      genome-wide expression data across the mouse brain from the Allen Brain Atlas
      (ABA). The central fear circuitry, as defined by subnuclei of the amygdala, the
      afferent hippocampus, the medial prefrontal cortex and the efferent
      periaqueductal gray, was enriched with metabolic receptors. Some of their
      corresponding ligands were known to modulate fear (e.g., estrogen and thyroid
      hormones) while others had not been associated with fear before (e.g., glucagon,
      ACTH). Additionally, several of these enriched metabolic receptors were
      coexpressed with well-described fear-modulating genes (Crh, Crhr1, or Crhr2). Co
      expression analysis of monoamine markers and metabolic receptors suggested that
      monoaminergic nuclei have differential sensitivity to metabolic alterations.
      Serotonergic neurons expressed a large number of metabolic receptors (e.g.,
      estrogen receptors, fatty acid receptors), suggesting a wide responsivity to
      metabolic changes. The noradrenergic system seemed to be specifically sensitive
      to hypocretin/orexin modulation. Taken together, we identified a number of novel
      metabolic factors (glucagon, ACTH) that have the potential to modulate the fear
      response. We additionally propose novel cerebral targets for metabolic factors
      (e.g., thyroid hormones) that modulate fear, but of which the sites of action are
      (largely) unknown.

PMID- 30210280
TI  - Pathophysiological Changes of Physical Barriers of Peripheral Nerves After
      Injury.
AB  - Peripheral nerves are composed of complex layered anatomical structures,
      including epineurium, perineurium, and endoneurium. Perineurium and endoneurium
      contain many physical barriers, including the blood-nerve barrier at endoneurial
      vessels and the perineurial barrier. These physical barriers help to eliminate
      flux penetration and thus contribute to the establishment of a stable
      microenvironment. In the current review, we introduce the anatomical compartments
      and physical barriers of peripheral nerves and then describe the cellular and
      molecular basis of peripheral physical barriers. We also specifically explore
      peripheral nerve injury-induced changes of peripheral physical barriers,
      including elevated endoneurial fluid pressure, increased leakage of tracer,
      decreased barrier-type endothelial cell ratio, and altered distributions and
      expressions of cellular junctional proteins. The understanding of the
      pathophysiological changes of physical barriers following peripheral nerve injury
      may provide a clue for the treatment of peripheral nerve injury.

PMID- 30210281
TI  - Cortical Surface Area Rather Than Cortical Thickness Potentially Differentiates
      Radiation Encephalopathy at Early Stage in Patients With Nasopharyngeal
      Carcinoma.
AB  - Radiation encephalopathy (RE) is one of the most severe complications in
      nasopharyngeal carcinoma (NPC) patients after radiotherapy (RT). However, the
      morphological alteration of early RE is insufficiently investigated. We aimed to
      investigate the cortical thickness and surface area alterations in NPC patients
      with or without RE in the follow-up. A total of 168 NPC patients each underwent a
      single scan and analysis at various times either Pre-RT (n = 56) or Post-RT (n =
      112). We further divided the Post-RT NPC patients into three groups based on the
      time of the analysis following RT (Post-RTwithin 6 months and Post-RT7-12 months)
      or whether RE signs were detected in the analysis (Post-RTRE proved in follow
      up). We confined the vertex-wise analyses of the cortical thickness and surface
      area to the bilateral temporal lobes. Interestingly, we revealed a gradual
      increase in the cortical surface area of the temporal lobe with increasing time
      after RT within the Post-RTRE proved in follow-up group, consistent with the
      between-group findings, which showed a significant increase in cortical surface
      area in the Post-RTRE proved in follow-up group relative to the Pre-RT group and
      the Post-RTwithin 6 months group. By contrast, such a trend was not observed in
      the cortical thickness findings. We concluded that the cortical surface area,
      rather than cortical thickness, may serve as a potential biomarker for early
      diagnosis of RE.

PMID- 30210284
TI  - Task-Evoked Dynamic Network Analysis Through Hidden Markov Modeling.
AB  - Complex thought and behavior arise through dynamic recruitment of large-scale
      brain networks. The signatures of this process may be observable in
      electrophysiological data; yet robust modeling of rapidly changing functional
      network structure on rapid cognitive timescales remains a considerable challenge.
      Here, we present one potential solution using Hidden Markov Models (HMMs), which
      are able to identify brain states characterized by engaging distinct functional
      networks that reoccur over time. We show how the HMM can be inferred on
      continuous, parcellated source-space Magnetoencephalography (MEG) task data in an
      unsupervised manner, without any knowledge of the task timings. We apply this to
      a freely available MEG dataset in which participants completed a face perception
      task, and reveal task-dependent HMM states that represent whole-brain dynamic
      networks transiently bursting at millisecond time scales as cognition unfolds.
      The analysis pipeline demonstrates a general way in which the HMM can be used to
      do a statistically valid whole-brain, group-level task analysis on MEG task data,
      which could be readily adapted to a wide range of task-based studies.

PMID- 30210283
TI  - MicroRNA-298 Reverses Multidrug Resistance to Antiepileptic Drugs by Suppressing
      MDR1/P-gp Expression in vitro.
AB  - P-glycoprotein (P-gp), a critical multidrug transporter, recognizes and
      transports various antiepileptic drugs (AEDs) through the blood-brain barrier
      (BBB). This may decrease the concentrations of AEDs in brain tissues and cause
      multidrug resistance (MDR) in patients with refractory epilepsy. Compelling
      evidence indicates that microRNAs (miRNAs) modulate MDR in various cancers by
      regulating P-gp expression. Furthermore, a previous study showed that miR-298
      mediates MDR in breast cancer cells by downregulating P-gp expression. Based on
      the therapeutic results obtained from tumor cells, we aimed to determine whether
      miR-298 reverses MDR to AEDs by regulating P-gp expression in the BBB. We first
      established different drug-resistant cell lines, including PHT-resistant HBMECs
      (human brain microvascular endothelial cells) and doxorubicin (DOX)-resistant U87
      MG (human malignant glioma) cells, by inducing P-gp overexpression. Quantitative
      real-time PCR (qRT-PCR) analysis revealed reduced expression of miR-298 in both
      HBMEC/PHT and U87-MG/DOX cells, and the luciferase reporter assay identified the
      direct binding of miR-298 to the 3'-untranslated region (3'-UTR) of P-gp.
      Moreover, ectopic expression of miR-298 downregulated P-gp expression at the mRNA
      and protein levels, thereby increasing the intracellular accumulation of AEDs in
      drug-resistant HBMEC/PHT and U87-MG/DOX cells. Thus, our findings suggest that
      miR-298 reverses MDR to AEDs by inhibiting P-gp expression, suggesting a
      potential target for overcoming MDR in refractory epilepsy.

PMID- 30210282
TI  - The Contribution of Primary Auditory Cortex to Auditory Categorization in
      Behaving Monkeys.
AB  - The specific contribution of core auditory cortex to auditory perception -such as
      categorization- remains controversial. To identify a contribution of the primary
      auditory cortex (A1) to perception, we recorded A1 activity while monkeys
      reported whether a temporal sequence of tone bursts was heard as having a "small"
      or "large" frequency difference. We found that A1 had frequency-tuned responses
      that habituated, independent of frequency content, as this auditory sequence
      unfolded over time. We also found that A1 firing rate was modulated by the
      monkeys' reports of "small" and "large" frequency differences; this modulation
      correlated with their behavioral performance. These findings are consistent with
      the hypothesis that A1 contributes to the processes underlying auditory
      categorization.

PMID- 30210285
TI  - Longitudinal in vivo Diffusion Tensor Imaging Detects Differential
      Microstructural Alterations in the Hippocampus of Chronic Social Defeat Stress
      Susceptible and Resilient Mice.
AB  - Background: Microstructural alterations in the hippocampus may underlie stress
      related disorders and stress susceptibility. However, whether these alterations
      are pre-existing stress vulnerability biomarkers or accumulative results of
      chronic stress remain unclear. Moreover, examining the whole hippocampus as one
      unit and ignoring the possibility of a lateralized effect of stress may mask some
      stress effects and contribute to the heterogeneity of previous findings. Methods:
      After C57BL/6 mice were exposed to a 10-day chronic social defeat stress (CSDS)
      paradigm, different stress phenotypes, i.e., susceptible (n = 10) and resilient
      (n = 7) mice, were discriminated by the behavior of the mice in a social
      interaction test. With in vivo diffusion tensor imaging (DTI) scans that were
      conducted both before and after the stress paradigm, we evaluated diffusion
      properties in the left and right, dorsal (dHi) and ventral hippocampus (vHi) of
      experimental mice. Results: A significantly lower fractional anisotropy (FA) was
      found in the right vHi of the susceptible mice prior to the CSDS paradigm than
      that found in the resilient mice, suggesting that pre-existing microstructural
      abnormalities may result in stress susceptibility. However, no significant group
      differences were found in the post-stress FA values of any of the hippocampal
      regions of interest (ROIs). In addition, mean diffusivity (MD) and radial
      diffusivity (RD) values were found to be significantly greater only in the right
      dHi of the resilient group compared to those of the susceptible mice.
      Furthermore, a significant longitudinal decrease was only observed in the right
      dHi RD value of the susceptible mice. Moreover, the social interaction (SI) ratio
      was positively related to post-stress left MD, right dHi MD, and right dHi RD
      values and the longitudinal right dHi MD percent change. Meanwhile, a negative
      relationship was detected between the SI ratio and bilateral mean of the post
      stress left relative to right vHi FA value, highlighting the important role of
      right hippocampus in stress-resilience phenotype. Conclusion: Our findings
      demonstrated different longitudinal microstructural alterations in the bilateral
      dHi and vHi between stress-susceptible and resilient subgroups and indicated a
      right-sided lateralized stress effect, which may be useful in the diagnosis and
      prevention of stress-related disorders as well as their intervention.

PMID- 30210286
TI  - Dysregulation of Astrocytic HMGB1 Signaling in Amyotrophic Lateral Sclerosis.
AB  - Astrocytes have emerged as critical elements for the maintenance and function of
      the central nervous system. The expression on their cell membrane of RAGE and
      TLR4 receptors makes astrocytes susceptible to High-mobility group box 1 (HMGB1),
      a nuclear protein typically released in the extracellular milieu by living cells
      experiencing physiological stress conditions or by damaged cells. Here, we show
      that the interaction of HMGB1 with normal spinal cord astrocytes induces the
      astrocytic production of neurotrophic factors, particularly brain-derived
      neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor
      (GDNF). Multiple investigations suggest a role for HMGB1 in amyotrophic lateral
      sclerosis (ALS). Yet, no mechanistic information on the implication of HMGB1
      signaling in this disorder is currently available. We demonstrate that non
      transgenic and transgenic SOD1WT spinal motor neurons exhibit only a basal
      nucleus-to-cytoplasm shuttling of the HMGB1 protein. Conversely, in SOD1G93A ALS
      mouse spinal cords, HMGB1 significantly translocates from the nucleus to the
      cytoplasm of motor neurons, thereby suggesting that it may be eventually released
      in the extracellular environment during the progression of the disease. We
      postulate that extracellular HMGB1 can paracrinally interact with the neighboring
      astrocytes in an attempt to counteract the neurodegenerative process. Yet, at
      variance with normal cells, SOD1G93A-expressing astrocytes show impaired capacity
      to raise BDNF and GDNF levels upon HMGB1 stimulation. Our data suggest that HMGB1
      have a potential to promote neuroprotective actions by healthy astrocytes.
      However, this neurotrophic response is disrupted in ALS astrocytes. This
      indicates that diseased astroglial cells may exacerbate motor neuron degeneration
      in ALS because of the loss of their neurosupportive functions.

PMID- 30210287
TI  - Dysregulation of MicroRNAs and Target Genes Networks in Peripheral Blood of
      Patients With Sporadic Amyotrophic Lateral Sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative
      disease. While genetics and other factors contribute to ALS pathogenesis,
      critical knowledge is still missing and validated biomarkers for monitoring the
      disease activity have not yet been identified. To address those aspects we
      carried out this study with the primary aim of identifying possible miRNAs/mRNAs
      dysregulation associated with the sporadic form of the disease (sALS).
      Additionally, we explored miRNAs as modulating factors of the observed clinical
      features. Study included 56 sALS and 20 healthy controls (HCs). We analyzed the
      peripheral blood samples of sALS patients and HCs with a high-throughput next
      generation sequencing followed by an integrated bioinformatics/biostatistics
      analysis. Results showed that 38 miRNAs (let-7a-5p, let-7d-5p, let-7f-5p, let-7g
      5p, let-7i-5p, miR-103a-3p, miR-106b-3p, miR-128-3p, miR-130a-3p, miR-130b-3p,
      miR-144-5p, miR-148a-3p, miR-148b-3p, miR-15a-5p, miR-15b-5p, miR-151a-5p, miR
      151b, miR-16-5p, miR-182-5p, miR-183-5p, miR-186-5p, miR-22-3p, miR-221-3p, miR
      223-3p, miR-23a-3p, miR-26a-5p, miR-26b-5p, miR-27b-3p, miR-28-3p, miR-30b-5p,
      miR-30c-5p, miR-342-3p, miR-425-5p, miR-451a, miR-532-5p, miR-550a-3p, miR-584
      5p, miR-93-5p) were significantly downregulated in sALS. We also found that
      different miRNAs profiles characterized the bulbar/spinal onset and the
      progression rate. This observation supports the hypothesis that miRNAs may impact
      the phenotypic expression of the disease. Genes known to be associated with ALS
      (e.g., PARK7, C9orf72, ALS2, MATR3, SPG11, ATXN2) were confirmed to be
      dysregulated in our study. We also identified other potential candidate genes
      like LGALS3 (implicated in neuroinflammation) and PRKCD (activated in
      mitochondrial-induced apoptosis). Some of the downregulated genes are involved in
      molecular bindings to ions (i.e., metals, zinc, magnesium) and in ions-related
      functions. The genes that we found upregulated were involved in the immune
      response, oxidation-reduction, and apoptosis. These findings may have important
      implication for the monitoring, e.g., of sALS progression and therefore represent
      a significant advance in the elucidation of the disease's underlying molecular
      mechanisms. The extensive multidisciplinary approach we applied in this study was
      critically important for its success, especially in complex disorders such as
      sALS, wherein access to genetic background is a major limitation.

PMID- 30210289
TI  - Cannabinoid 1 Receptor Signaling on Hippocampal GABAergic Neurons Influences
      Microglial Activity.
AB  - Microglia, the resident immune cells of the brain, play important roles in
      defending the brain against pathogens and supporting neuronal circuit plasticity.
      Chronic or excessive pro-inflammatory responses of microglia damage neurons,
      therefore their activity is tightly regulated. Pharmacological and genetic
      studies revealed that cannabinoid type 1 (CB1) receptor activity influences
      microglial activity, although microglial CB1 receptor expression is very low and
      activity-dependent. The CB1 receptor is mainly expressed on neurons in the
      central nervous system (CNS)-with an especially high level on GABAergic
      interneurons. Here, we determined whether CB1 signaling on this neuronal cell
      type plays a role in regulating microglial activity. We compared microglia
      density, morphology and cytokine expression in wild-type (WT) and GABAergic
      neuron-specific CB1 knockout mice (GABA/CB1-/-) under control conditions (saline
      treatment) and after 3 h, 24 h or repeated lipopolysaccharide (LPS)-treatment.
      Our results revealed that hippocampal microglia from saline-treated GABA/CB1-/-
      mice resembled those of LPS-treated WT mice: enhanced density and larger cell
      bodies, while the size and complexity of their processes was reduced. No further
      reduction in the size or complexity of microglia branching was detected after LPS
      treatment in GABA/CB1-/- mice, suggesting that microglia in naive GABA/CB1-/-
      mice were already in an activated state. This result was further supported by
      correlating the level of microglial tumor necrosis factor alpha (TNFalpha) with
      their size. Acute LPS-treatment elicited in both genotypes similar changes in the
      expression of pro-inflammatory cytokines (TNFalpha, interleukin-6 (IL-6) and
      interleukin 1beta (IL-1beta)). However, TNFalpha expression was still
      significantly elevated after repeated LPS-treatment in WT, but not in GABA/CB1-/-
      mice, indicating a faster development of tolerance to LPS. We also tested the
      possibility that the altered microglia activity in GABA/CB1-/- mice was due to an
      altered expression of neuron-glia interaction proteins. Indeed, the level of
      fractalkine (CX3CL1), a neuronal protein involved in the regulation of microglia,
      was reduced in hippocampal GABAergic neurons in GABA/CB1-/- mice, suggesting a
      disturbed neuronal control of microglial activity. Our result suggests that CB1
      receptor agonists can modulate microglial activity indirectly, through CB1
      receptors on GABAergic neurons. Altogether, we demonstrated that GABAergic
      neurons, despite their relatively low density in the hippocampus, have a specific
      role in the regulation of microglial activity and cannabinoid signaling plays an
      important role in this arrangement.

PMID- 30210292
TI  - Phosphorylation of the Amyloid-Beta Peptide Inhibits Zinc-Dependent Aggregation,
      Prevents Na,K-ATPase Inhibition, and Reduces Cerebral Plaque Deposition.
AB  - The triggers of late-onset sporadic Alzheimer's disease (AD) are still poorly
      understood. Impairment of protein phosphorylation with age is well-known;
      however, the role of the phosphorylation in beta-amyloid peptide (Abeta) is not
      studied sufficiently. Zinc-induced oligomerization of Abeta represents a
      potential seeding mechanism for the formation of neurotoxic Abeta oligomers and
      aggregates. Phosphorylation of Abeta by Ser8 (pS8-Abeta), localized inside the
      zinc-binding domain of the peptide, may significantly alter its zinc-induced
      oligomerization. Indeed, using dynamic light scattering, we have shown that
      phosphorylation by Ser8 dramatically reduces zinc-induced aggregation of Abeta,
      and moreover pS8-Abeta suppresses zinc-driven aggregation of non-modified Abeta
      in an equimolar mixture. We have further analyzed the effect of pS8-Abeta on the
      progression of cerebral amyloidosis with serial retro-orbital injections of the
      peptide in APPSwe/PSEN1dE9 murine model of AD, followed by histological analysis
      of amyloid burden in hippocampus. Unlike the non-modified Abeta that has no
      influence on the amyloidosis progression in murine models of AD, pS8-Abeta
      injections reduced the number of amyloid plaques in the hippocampus of mice by
      one-third. Recently shown inhibition of Na+,K+-ATPase activity by Abeta, which is
      thought to be a major contributor to neuronal dysfunction in AD, is completely
      reversed by phosphorylation of the peptide. Thus, several AD-associated
      pathogenic properties of Abeta are neutralized by its phosphorylation.

PMID- 30210290
TI  - Molecular Mechanisms of Lithium Action: Switching the Light on Multiple Targets
      for Dementia Using Animal Models.
AB  - Lithium has long been used for the treatment of psychiatric disorders, due to its
      robust beneficial effect as a mood stabilizing drug. Lithium's effectiveness for
      improving neurological function is therefore well-described, stimulating the
      investigation of its potential use in several neurodegenerative conditions
      including Alzheimer's (AD), Parkinson's (PD) and Huntington's (HD) diseases. A
      narrow therapeutic window for these effects, however, has led to concerted
      efforts to understand the molecular mechanisms of lithium action in the brain, in
      order to develop more selective treatments that harness its neuroprotective
      potential whilst limiting contraindications. Animal models have proven pivotal in
      these studies, with lithium displaying advantageous effects on behavior across
      species, including worms (C. elegans), zebrafish (Danio rerio), fruit flies
      (Drosophila melanogaster) and rodents. Due to their susceptibility to genetic
      manipulation, functional genomic analyses in these model organisms have provided
      evidence for the main molecular determinants of lithium action, including
      inhibition of inositol monophosphatase (IMPA) and glycogen synthase kinase-3 (GSK
      3). Accumulating pre-clinical evidence has indeed provided a basis for research
      into the therapeutic use of lithium for the treatment of dementia, an area of
      medical priority due to its increasing global impact and lack of disease
      modifying drugs. Although lithium has been extensively described to prevent AD
      associated amyloid and tau pathologies, this review article will focus on generic
      mechanisms by which lithium preserves neuronal function and improves memory in
      animal models of dementia. Of these, evidence from worms, flies and mice points
      to GSK-3 as the most robust mediator of lithium's neuro-protective effect, but
      it's interaction with downstream pathways, including Wnt/beta-catenin, CREB/brain
      derived neurotrophic factor (BDNF), nuclear factor (erythroid-derived 2)-like 2
      (Nrf2) and toll-like receptor 4 (TLR4)/nuclear factor-kappaB (NFkappaB), have
      identified multiple targets for development of drugs which harness lithium's
      neurogenic, cytoprotective, synaptic maintenance, anti-oxidant, anti-inflammatory
      and protein homeostasis properties, in addition to more potent and selective GSK
      3 inhibitors. Lithium, therefore, has advantages as a multi-functional therapy to
      combat the complex molecular pathology of dementia. Animal studies will be vital,
      however, for comparative analyses to determine which of these defense mechanisms
      are most required to slow-down cognitive decline in dementia, and whether
      combination therapies can synergize systems to exploit lithium's neuro-protective
      power while avoiding deleterious toxicity.

PMID- 30210291
TI  - Gene Therapy in Mouse Models of Deafness and Balance Dysfunction.
AB  - Therapeutic strategies to restore hearing and balance in mouse models of inner
      ear disease aim to rescue sensory function by gene replacement, augmentation,
      knock down or knock out. Modalities to achieve therapeutic effects have utilized
      virus-mediated transfer of wild type genes and small interfering ribonucleic
      acids; systemic and focal administration of antisense oligonucleotides (ASO) and
      designer small molecules; and lipid-mediated transfer of Cas 9 ribonucleoprotein
      (RNP) complexes. This work has established that gene or drug administration to
      the structurally and functionally immature, early neonatal mouse inner ear prior
      to hearing onset is a prerequisite for the most robust therapeutic responses.
      These observations may have significant implications for translating mouse inner
      ear gene therapies to patients. The human fetus hears by gestational week 19,
      suggesting that a corollary window of therapeutic efficacy closes early in the
      second trimester of pregnancy. We hypothesize that fetal therapeutics deployed
      prior to hearing onset may be the most effective approach to preemptively manage
      genetic mutations that cause deafness and vestibular dysfunction. We assert that
      gene therapy studies in higher vertebrate model systems with fetal hearing onset
      and a comparable acoustic range and sensitivity to that of humans are an
      essential step to safely and effectively translate murine gene therapies to the
      clinic.

PMID- 30210288
TI  - Zebrafish Models of Neurodevelopmental Disorders: Past, Present, and Future.
AB  - Zebrafish are increasingly being utilized as a model system to investigate the
      function of the growing list of risk genes associated with neurodevelopmental
      disorders. This is due in large part to the unique features of zebrafish that
      make them an optimal system for this purpose, including rapid, external
      development of transparent embryos, which enable the direct visualization of the
      developing nervous system during early stages, large progenies, which provide
      considerable tractability for performing high-throughput pharmacological screens
      to identify small molecule suppressors of simple behavioral phenotypes, and ease
      of genetic manipulation, which has been greatly facilitated by the advent of
      CRISPR/Cas9 gene editing technologies. This review article focuses on studies
      that have harnessed these advantages of the zebrafish system for the functional
      analysis of genes that are strongly associated with the following
      neurodevelopmental disorders: autism spectrum disorders (ASD), epilepsy,
      intellectual disability (ID) and schizophrenia. We focus primarily on studies
      describing early morphological and behavioral phenotypes during embryonic and
      larval stages resulting from loss of risk gene function. We highlight insights
      into basic mechanisms of risk gene function gained from these studies as well as
      limitations of studies to date. Finally, we discuss advances in in vivo neural
      circuit imaging in zebrafish, which promise to transform research using the
      zebrafish model by illuminating novel circuit-level mechanisms with relevance to
      neurodevelopmental disorders.

PMID- 30210293
TI  - Post-transcriptional Processing of mRNA in Neurons: The Vestiges of the RNA World
      Drive Transcriptome Diversity.
AB  - Neurons are morphologically complex cells that rely on the compartmentalization
      of protein expression to develop and maintain their extraordinary
      cytoarchitecture. This formidable task is achieved, at least in part, by
      targeting mRNA to subcellular compartments where they are rapidly translated.
      mRNA transcripts are the conveyor of genetic information from DNA to the
      translational machinery, however, they are also endowed with additional functions
      linked to both the coding sequence (open reading frame, or ORF) and the flanking
      5' and 3' untranslated regions (UTRs), that may harbor coding-independent
      functions. In this review, we will highlight recent evidences supporting new
      coding-dependent and -independent functions of mRNA and discuss how nuclear and
      cytoplasmic post-transcriptional modifications of mRNA contribute to localization
      and translation in mammalian cells with specific emphasis on neurons. We also
      describe recently developed techniques that can be employed to study RNA dynamics
      at subcellular level in eukaryotic cells in developing and regenerating neurons.

PMID- 30210295
TI  - Distinct Modulation of Spontaneous and GABA-Evoked Gating by Flurazepam Shapes
      Cross-Talk Between Agonist-Free and Liganded GABAA Receptor Activity.
AB  - GABAA receptors (GABAARs) play a crucial inhibitory role in the CNS.
      Benzodiazepines (BDZs) are positive modulators of specific subtypes of GABAARs,
      but the underlying mechanism remains obscure. Early studies demonstrated the
      major impact of BDZs on binding and more recent investigations indicated gating,
      but it is unclear which transitions are affected. Moreover, the upregulation of
      GABAAR spontaneous activity by BDZs indicates their impact on receptor gating but
      the underlying mechanisms remain unknown. Herein, we investigated the effect of a
      BDZ (flurazepam) on the spontaneous and GABA-induced activity for wild-type (WT,
      alpha1beta2gamma2) and mutated (at the orthosteric binding site alpha1F64)
      GABAARs. Surprisingly, in spite of the localization at the binding site, these
      mutations increased the spontaneous activity. Flurazepam (FLU) upregulated this
      activity for mutants and WT receptors to a similar extent by affecting
      opening/closing transitions. Spontaneous activity affected GABA-evoked currents
      and is manifested as an overshoot after agonist removal that depended on the
      modulation by BDZs. We explain the mechanism of this phenomenon as a cross
      desensitization of ligand-activated and spontaneously active receptors. Moreover,
      due to spontaneous activity, FLU-pretreatment and co-application (agonist + FLU)
      protocols yielded distinct results. We provide also the first evidence that
      GABAAR may enter the desensitized state in the absence of GABA in a FLU-dependent
      manner. Based on our data and model simulations, we propose that FLU affects
      agonist-induced gating by modifying primarily preactivation and desensitization.
      We conclude that the mechanisms of modulation of spontaneous and ligand-activated
      GABAAR activity concerns gating but distinct transitions are affected in
      spontaneous and agonist-evoked activity.

PMID- 30210296
TI  - Counter-Balance Between Gli3 and miR-7 Is Required for Proper Morphogenesis and
      Size Control of the Mouse Brain.
AB  - Brain morphogenesis requires precise regulation of multiple genes to control
      specification of distinct neural progenitors (NPs) and neuronal production.
      Dysregulation of these genes results in severe brain malformation such as
      macrocephaly and microcephaly. Despite studies of the effect of individual
      pathogenic genes, the counter-balance between multiple factors in controlling
      brain size remains unclear. Here we show that cortical deletion of Gli3 results
      in enlarged brain and folding structures in the cortical midline at the postnatal
      stage, which is mainly caused by the increased percentage of intermediate
      progenitors (IPs) and newborn neurons. In addition, dysregulation of neuronal
      migration also contributes to the folding defects in the cortical midline region.
      Knockdown of microRNA (miRNA) miR-7 can rescue abnormal brain morphology in Gli3
      knockout mice by recovering progenitor specification, neuronal production and
      migration through a counter-balance of the Gli3 activity. Moreover, miR-7 likely
      exerts its function through silencing target gene Pax6. Our results indicate that
      proper brain morphogenesis is an outcome of interactive regulations of multiple
      molecules such as Gli3 and miR-7. Because miRNAs are easy to synthesize and
      deliver, miR-7 could be a potential therapeutic means to macrocephaly caused by
      Gli3-deficiency.

PMID- 30210298
TI  - Typology and Circuitry of Suppressed-by-Contrast Retinal Ganglion Cells.
AB  - Retinal ganglion cells (RGCs) relay ~40 parallel and independent streams of
      visual information, each encoding a specific feature of a visual scene, to the
      brain for further processing. The polarity of a visual neuron's response to a
      change in contrast is generally the first characteristic used for functional
      classification: ON cells increase their spike rate to positive contrast; OFF
      cells increase their spike rate for negative contrast; ON-OFF cells increase
      their spike rate for both contrast polarities. Suppressed-by-Contrast (SbC)
      neurons represent a less well-known fourth category; they decrease firing below a
      baseline rate for both positive and negative contrasts. SbC RGCs were discovered
      over 50 years ago, and SbC visual neurons have now been found in the thalamus and
      primary visual cortex of several mammalian species, including primates. Recent
      discoveries of SbC RGCs in mice have provided new opportunities for tracing
      upstream circuits in the retina responsible for the SbC computation and
      downstream targets in the brain where this information is used. We review and
      clarify recent work on the circuit mechanism of the SbC computation in these
      RGCs. Studies of mechanism rely on precisely defined cell types, and we argue
      that, like ON, OFF, and ON-OFF RGCs, SbC RGCs consist of more than one type. A
      new appreciation of the diversity of SbC RGCs will help guide future work on
      their targets in the brain and their roles in visual perception and behavior.

PMID- 30210297
TI  - The Free Radical Scavenger N-Tert-Butyl-alpha-Phenylnitrone (PBN) Administered to
      Immature Rats During Status Epilepticus Alters Neurogenesis and Has Variable
      Effects, Both Beneficial and Detrimental, on Long-Term Outcomes.
AB  - Status epilepticus (SE), especially in immature animals, is known to produce
      recurrent spontaneous seizures and behavioral comorbidities later in life. The
      cause of these adverse long-term outcomes is unknown, but it has been
      hypothesized that free radicals produced by SE may play a role. We tested this
      hypothesis by treating immature (P25) rats with the free radical scavenger N-tert
      butyl-alpha-phenylnitrone (PBN) at the time of lithium chloride
      (LiCl)/pilocarpine (PILO)-induced SE. Later, long-term outcomes were assessed.
      Cognitive impairment (spatial memory) was tested in the Morris water maze (MWM).
      Emotional disturbances were assessed by the capture test (aggressiveness) and
      elevated plus maze's (EPM) test (anxiety). Next, the presence and severity of
      spontaneous seizures were assessed by continuous video/EEG monitoring for 5 days.
      Finally, immunochemistry, stereology and morphology were used to assess the
      effects of PBN on hippocampal neuropathology and neurogenesis. PBN treatment
      modified the long-term effects of SE in varying ways, some beneficial and some
      detrimental. Beneficially, PBN protected against severe anatomical damage in the
      hippocampus and associated spatial memory impairment. Detrimentally, PBN treated
      animals had more severe seizures later in life. PBN also made animals more
      aggressive and more anxious. Correlating with these detrimental long-term
      outcomes, PBN significantly modified post-natal neurogenesis. Treated animals had
      significantly increased numbers of mature granule cells (GCs) ectopically located
      in the dentate hilus (DH). These results raise the possibility that abnormal
      neurogenesis may significantly contribute to the development of post-SE epilepsy
      and behavioral comorbidities.

PMID- 30210299
TI  - Mechanism of BDNF Modulation in GABAergic Synaptic Transmission in Healthy and
      Disease Brains.
AB  - In the mature healthy mammalian neuronal networks, gamma-aminobutyric acid (GABA)
      mediates synaptic inhibition by acting on GABAA and GABAB receptors (GABAAR,
      GABABR). In immature networks and during numerous pathological conditions the
      strength of GABAergic synaptic inhibition is much less pronounced. In these
      neurons the activation of GABAAR produces paradoxical depolarizing action that
      favors neuronal network excitation. The depolarizing action of GABAAR is a
      consequence of deregulated chloride ion homeostasis. In addition to depolarizing
      action of GABAAR, the GABABR mediated inhibition is also less efficient. One of
      the key molecules regulating the GABAergic synaptic transmission is the brain
      derived neurotrophic factor (BDNF). BDNF and its precursor proBDNF, can be
      released in an activity-dependent manner. Mature BDNF operates via its cognate
      receptors tropomyosin related kinase B (TrkB) whereas proBDNF binds the p75
      neurotrophin receptor (p75NTR). In this review article, we discuss recent finding
      illuminating how mBDNF-TrkB and proBDNF-p75NTR signaling pathways regulate GABA
      related neurotransmission under physiological conditions and during epilepsy.

PMID- 30210294
TI  - Neurotoxic Agent-Induced Injury in Neurodegenerative Disease Model: Focus on
      Involvement of Glutamate Receptors.
AB  - Glutamate receptors play a crucial role in the central nervous system and are
      implicated in different brain disorders. They play a significant role in the
      pathogenesis of neurodegenerative diseases (NDDs) such as Alzheimer's disease,
      Parkinson's disease, and amyotrophic lateral sclerosis. Although many studies on
      NDDs have been conducted, their exact pathophysiological characteristics are
      still not fully understood. In in vivo and in vitro models of neurotoxic-induced
      NDDs, neurotoxic agents are used to induce several neuronal injuries for the
      purpose of correlating them with the pathological characteristics of NDDs.
      Moreover, therapeutic drugs might be discovered based on the studies employing
      these models. In NDD models, different neurotoxic agents, namely, kainic acid,
      domoic acid, glutamate, beta-N-Methylamino-L-alanine, amyloid beta, 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine, 1-methyl-4-phenylpyridinium, rotenone, 3
      Nitropropionic acid and methamphetamine can potently impair both ionotropic and
      metabotropic glutamate receptors, leading to the progression of toxicity. Many
      other neurotoxic agents mainly affect the functions of ionotropic glutamate
      receptors. We discuss particular neurotoxic agents that can act upon glutamate
      receptors so as to effectively mimic NDDs. The correlation of neurotoxic agent
      induced disease characteristics with glutamate receptors would aid the discovery
      and development of therapeutic drugs for NDDs.

PMID- 30210300
TI  - Electrophysiological Effects of Ghrelin in the Hypothalamic Paraventricular
      Nucleus Neurons.
AB  - The paraventricular nucleus (PVN) is involved in the control of sympathetic tone
      and the secretion of hormones, both functions known to be influenced by ghrelin,
      suggesting direct effect of ghrelin in this nucleus. However, the effects of
      ghrelin on the excitability of different PVN neuronal populations have not been
      demonstrated. This study assessed the effects of ghrelin on the activity of PVN
      neurons, correlating the responses to subpopulations of PVN neurons. We used a 64
      multielectrode array to examine the effects of ghrelin administration on
      extracellular spike frequency in PVN neurons recorded in brain slices obtained
      from male Sprague-Dawley rats. Bath administration of 10 nM ghrelin increased
      (29/97, 30%) or decreased (37/97, 38%) spike frequency in PVN neurons. The GABAA
      and glutamate receptors antagonists abolish the decrease in spike frequency,
      without changes in the proportion of increases in spike frequency (23/53, 43%)
      induced by ghrelin. The results indicate a direct effect of ghrelin increasing
      PVN neurons activity and a synaptic dependent effect decreasing PVN neurons
      activity. The patch clamp recordings showed similar proportions of PVN neurons
      influenced by 10 nM ghrelin (33/95, 35% depolarized; 29/95, 30% hyperpolarized).
      Using electrophysiological fingerprints to identify specific subpopulations of
      PVN neurons we observed that the majority of pre-autonomic neurons (11/18 -61%)
      were depolarized by ghrelin, while both neuroendocrine (29% depolarizations, 40%
      hyperpolarizations), and magnocellular neurons (29% depolarizations, 21%
      hyperpolarizations) showed mixed responses. Finally, to correlate the
      electrophysiological response and the neurochemical phenotype of PVN neurons,
      cell cytoplasm was collected after recordings and RT-PCR performed to assess the
      presence of mRNA for vasopressin, oxytocin, thyrotropin (TRH) and corticotropin
      (CRH) releasing hormones. The single-cell RT-PCR showed that most TRH-expressing
      (4/5) and CRH-expressing (3/4) neurons are hyperpolarized in response to ghrelin.
      In conclusion, ghrelin either directly increases or indirectly decreases the
      activity of PVN neurons, this suggests that ghrelin acts on inhibitory PVN
      neurons that, in turn, decrease the activity of TRH-expressing and CRH-expressing
      neurons in the PVN.

PMID- 30210301
TI  - The Ischemic Immature Brain: Views on Current Experimental Models.

PMID- 30210302
TI  - Contributions of the Hippocampal CA3 Circuitry to Acute Seizures and
      Hyperexcitability Responses in Mouse Models of Brain Ischemia.
AB  - The hippocampal circuitry is widely recognized as susceptible to ischemic injury
      and seizure generation. However, hippocampal contribution to acute non-convulsive
      seizures (NCS) in models involving middle cerebral artery occlusion (MCAO)
      remains to be determined. To address this, we occluded the middle cerebral artery
      in adult C57 black mice and monitored electroencephalographic (EEG) discharges
      from hippocampal and neocortical areas. Electrographic discharges in the absence
      of convulsive motor behaviors were observed within 90 min following occlusion of
      the middle cerebral artery. Hippocampal discharges were more robust than
      corresponding cortical discharges in all seizure events examined, and hippocampal
      discharges alone or with minimal cortical involvement were also observed in some
      seizure events. Seizure development was associated with ipsilateral hippocampal
      injuries as determined by subsequent histological examinations. We also
      introduced hypoxia-hypoglycemia episodes in mouse brain slices and examined
      regional hyperexcitable responses ex vivo. Extracellular recordings showed that
      the hippocampal CA3 region had a greater propensity for exhibiting
      single/multiunit activities or epileptiform field potentials following hypoxic
      hypoglycemic (HH) episodes compared to the CA1, dentate gyrus, entorhinal
      cortical (EC) or neocortical regions. Whole-cell recordings revealed that CA3
      pyramidal neurons exhibited excessive excitatory postsynaptic currents,
      attenuated inhibitory postsynaptic currents and intermittent or repetitive spikes
      in response to HH challenge. Together, these observations suggest that
      hippocampal discharges, possibly as a result of CA3 circuitry hyperexcitability,
      are a major component of acute NCS in a mouse model of MCAO.

PMID- 30210303
TI  - Changes in the Peripheral Chemosensory System Drive Adaptive Shifts in Food
      Preferences in Insects.
AB  - A key challenge in understanding the evolution of animal behaviors is to identify
      cellular and molecular mechanisms that underlie the evolution of adaptive traits
      and behaviors in polymorphic populations under local selection pressures. Despite
      recent advances in fish, mice, and insects, there are still only a few compelling
      examples of major genes and cellular mechanisms associated with complex
      behavioral changes. Shifts in food or host preferences in insects, accompanied by
      changes in the peripheral chemosensory system, offer some of the best examples of
      adaptive behavioral evolution. A remarkable example is the German cockroach,
      Blattella germanica, a major indoor pest with a highly diverse omnivorous diet.
      Strong and persistent selection pressure with toxic-baits has induced rapid
      evolution of behavioral resistance in multiple cockroach populations. While
      typical cockroaches detect and accept the sugar glucose as a feeding-stimulant,
      behaviorally resistant cockroaches avoid eating glucose-containing toxic baits by
      sensing glucose as a deterrent. We review the peripheral gustatory neural
      mechanisms of glucose-aversion and discuss how the rapid emergence of taste
      polymorphisms can impede pest control efforts and affect foraging and mate-choice
      in adapted cockroach populations.

PMID- 30210304
TI  - TASK1 and TASK3 Are Coexpressed With ASIC1 in the Ventrolateral Medulla and
      Contribute to Central Chemoreception in Rats.
AB  - The ventrolateral medulla (VLM), including the lateral paragigantocellular
      nucleus (LPGi) and rostral VLM (RVLM), is commonly considered to be a
      chemosensitive region. However, the specific mechanism of chemoreception in the
      VLM remains elusive. Acid-sensing ion channels (ASICs), a family of voltage
      independent proton-gated cation channels, can be activated by an external pH
      decrease to cause Na+ entry and induce neuronal excitability. TWIK-related acid
      sensitive potassium channels (TASKs) are members of another group of pH-sensitive
      channels; in contrast to AISICs, they can be stimulated by pH increases and are
      inhibited by pH decreases in the physiological range. Our previous study
      demonstrated that ASICs take part in chemoreception. The aims of this study are
      to explore whether TASKs participate in the acid sensitivity of neurons in the
      VLM, thereby cooperating with ASICs. Our research demonstrated that TASKs,
      including TASK1 and TASK3, are colocalized with ASIC1 in VLM neurons. Blocking
      TASKs by microinjection of the non-selective TASK antagonist bupivacaine (BUP),
      specific TASK1 antagonist anandamide (AEA) or specific TASK3 antagonist ruthenium
      red (RR) into the VLM increased the integrated phrenic nerve discharge (iPND),
      shortened the inspiratory time (Ti) and enhanced the respiratory drive (iPND/Ti).
      In addition, microinjection of artificial cerebrospinal fluid (ACSF) at a pH of
      7.0 or 6.5 prolonged Ti, increased iPND and enhanced respiratory drive, which
      were inhibited by the ASIC antagonist amiloride (AMI). By contrast,
      microinjection of alkaline ACSF decreased iPND and respiratory drive, which were
      inhibited by AEA. Taken together, our data suggest that TASK1 and TASK3 are
      coexpressed with ASIC1 in the VLM. Moreover, TASK1 and TASK3 contribute to the
      central regulation of breathing by coordinating with each other to perceive local
      pH changes; these results indicate a novel chemosensitive mechanism of the VLM.

PMID- 30210305
TI  - Targeting VGLUT2 in Mature Dopamine Neurons Decreases Mesoaccumbal Glutamatergic
      Transmission and Identifies a Role for Glutamate Co-release in Synaptic
      Plasticity by Increasing Baseline AMPA/NMDA Ratio.
AB  - Expression of the Vglut2/Slc17a6 gene encoding the Vesicular glutamate
      transporter 2 (VGLUT2) in midbrain dopamine (DA) neurons enables these neurons to
      co-release glutamate in the nucleus accumbens (NAc), a feature of putative
      importance to drug addiction. For example, it has been shown that conditional
      deletion of Vglut2 gene expression within developing DA neurons in mice causes
      altered locomotor sensitization to addictive drugs, such as amphetamine and
      cocaine, in adulthood. Alterations in DA neurotransmission in the mesoaccumbal
      pathway has been proposed to contribute to these behavioral alterations but the
      underlying molecular mechanism remains largely elusive. Repeated exposure to
      cocaine is known to cause lasting adaptations of excitatory synaptic transmission
      onto medium spiny neurons (MSNs) in the NAc, but the putative contribution of
      VGLUT2-mediated glutamate co-release from the mesoaccumbal projection has never
      been investigated. In this study, we implemented a tamoxifen-inducible Cre-LoxP
      strategy to selectively probe VGLUT2 in mature DA neurons of adult mice.
      Optogenetics-coupled patch clamp analysis in the NAc demonstrated a significant
      reduction of glutamatergic neurotransmission, whilst behavioral analysis revealed
      a normal locomotor sensitization to amphetamine and cocaine. When investigating
      if the reduced level of glutamate co-release from DA neurons caused a detectable
      post-synaptic effect on MSNs, patch clamp analysis identified an enhanced
      baseline AMPA/NMDA ratio in DA receptor subtype 1 (DRD1)-expressing accumbal MSNs
      which occluded the effect of cocaine on synaptic transmission. We conclude that
      VGLUT2 in mature DA neurons actively contributes to glutamatergic
      neurotransmission in the NAc, a finding which for the first time highlights
      VGLUT2-mediated glutamate co-release in the complex mechanisms of synaptic
      plasticity in drug addiction.

PMID- 30210307
TI  - Causal Role of Neural Signals Transmitted From the Frontal Eye Field to the
      Superior Colliculus in Saccade Generation.
AB  - The frontal eye field (FEF) and superior colliculus (SC) are major and well
      studied components of the oculomotor system. The FEF sends strong projections to
      the SC directly, and neurons in these brain regions transmit a variety of signals
      related to saccadic eye movements. Electrical microstimulation and
      pharmacological manipulation targeting the FEF or SC affect saccadic eye
      movements. These data suggest the causal contribution of each region to saccade
      generation. To understand how the brain generates behavior, however, it is
      critical not only to identify the structures and functions of individual regions,
      but also to elucidate how they interact with each other. In this review article,
      we first survey previous works that aimed at investigating whether and how the
      FEF and SC interact to regulate saccadic eye movements using electrophysiological
      and pharmacological techniques. These works have reported what signals FEF
      neurons transmit to the SC and what roles such signals play in regulating
      oculomotor behavior. We then highlight a recent attempt of our own that has
      applied an optogenetic approach to stimulate the neural pathway from the FEF to
      the SC in nonhuman primates. This study has shown that optogenetic stimulation of
      the FEF-SC pathway is sufficiently effective not only to modulate SC neuron
      activity, but also to evoke saccadic eye movements. Although the oculomotor
      system is a complex neural network composed of numbers of cortical and
      subcortical regions, the optogenetic approach will provide a powerful strategy
      for elucidating the role of each neural pathway constituting this network.

PMID- 30210308
TI  - Direct Glutamatergic Signaling From Midbrain Dopaminergic Neurons Onto Pyramidal
      Prefrontal Cortex Neurons.
AB  - The dopaminergic neurons of the ventral tegmental area (VTA) have been identified
      with the ability to co-release dopamine and glutamate. This ability was first
      documented in the nucleus accumbens but showed to be absent in the dorsal
      striatum. Recently the ability to release glutamate from a subpopulation of the
      VTA dopaminergic neurons has been shown to control the prefrontal cortex (PFC)
      excitation through the exclusive innervation of GABAergic fast spiking
      interneurons. Here, using an optogenetic approach, we expand this view by
      presenting that the VTA dopaminergic neurons do not only innervate interneurons
      but also pyramidal PFC neurons. This finding opens the range of possibilities for
      the VTA dopaminergic neurons to modulate the activity of PFC.

PMID- 30210309
TI  - Attention Configures Synchronization Within Local Neuronal Networks for
      Processing of the Behaviorally Relevant Stimulus.
AB  - The need for fast and dynamic processing of relevant information imposes high
      demands onto the flexibility and efficiency of the nervous system. A good example
      for such flexibility is the attention-dependent selection of relevant sensory
      information. Studies investigating attentional modulations of neuronal responses
      to simultaneously arriving input showed that neurons respond, as if only the
      attended stimulus would be present within their receptive fields (RF). However,
      attention also improves neuronal representation and behavioral performance, when
      only one stimulus is present. Thus, attention serves for selecting relevant input
      and changes the neuronal processing of signals representing selected stimuli,
      ultimately leading to a more efficient behavioral performance. Here, we tested
      the hypothesis that attention configures the strength of functional coupling
      between a local neuronal network's neurons specifically for effective processing
      of signals representing attended stimuli. This coupling is measured as the
      strength of gamma-synchronization between these neurons. The hypothesis predicts
      that the pattern of synchronization in local networks should depend on which
      stimulus is attended. Furthermore, we expect this pattern to be similar for the
      attended stimulus presented alone or together with irrelevant stimuli in the RF.
      To test these predictions, we recorded spiking-activity and local field
      potentials (LFP) with closely spaced electrodes in area V4 of monkeys performing
      a demanding attention task. Our results show that the gamma-band phase coherence
      (gamma-PhC) between spiking-activity and the LFP, as well as the spiking-activity
      of two groups of neurons, strongly depended on which of the two stimuli in the RF
      was attended. The gamma-PhC was almost identical for the attended stimulus
      presented either alone or together with a distractor. The functional relevance of
      dynamic gamma-band synchronization is further supported by the observation of
      strongly degraded gamma-PhC before behavioral errors, while firing rates were
      barely affected. These qualitatively different results point toward a failure of
      attention-dependent top-down mechanisms to correctly synchronize the local
      neuronal network in V4, even though this network receives the correctly selected
      input. These findings support the idea of a flexible, demand-dependent dynamic
      configuration of local neuronal networks, for performing different functions,
      even on the same sensory input.

PMID- 30210306
TI  - Evolution in Neuromodulation-The Differential Roles of Acetylcholine in Higher
      Order Association vs. Primary Visual Cortices.
AB  - This review contrasts the neuromodulatory influences of acetylcholine (ACh) on
      the relatively conserved primary visual cortex (V1), compared to the newly
      evolved dorsolateral prefrontal association cortex (dlPFC). ACh is critical both
      for proper circuit development and organization, and for optimal functioning of
      mature systems in both cortical regions. ACh acts through both nicotinic and
      muscarinic receptors, which show very different expression profiles in V1 vs.
      dlPFC, and differing effects on neuronal firing. Cholinergic effects mediate
      attentional influences in V1, enhancing representation of incoming sensory
      stimuli. In dlPFC ACh plays a permissive role for network communication. ACh
      receptor expression and ACh actions in higher visual areas have an intermediate
      profile between V1 and dlPFC. This changing role of ACh modulation across
      association cortices may help to illuminate the particular susceptibility of PFC
      in cognitive disorders, and provide therapeutic targets to strengthen cognition.

PMID- 30210310
TI  - Neuroimmune Activation Drives Multiple Brain States.
AB  - Neuroimmune signaling is increasingly identified as a critical component of
      neuronal processes underlying memory, emotion and cognition. The interactions of
      microglia and astrocytes with neurons and synapses, and the individual cytokines
      and immune signaling molecules that mediate these interactions are a current
      focus of much research. Here, we discuss neuroimmune activation as a mechanism
      triggering different states that modulate cognitive and affective processes to
      allow for appropriate behavior during and after illness or injury. We propose
      that these states lie on a continuum from a naive homeostatic baseline state in
      the absence of stimulation, to acute neuroimmune activity and chronic activation.
      Importantly, consequences of illness or injury including cognitive deficits and
      mood impairments can persist long after resolution of immune signaling. This
      suggests that neuroimmune activation also results in an enduring shift in the
      homeostatic baseline state with long lasting consequences for neural function and
      behavior. Such different states can be identified in a multidimensional way,
      using patterns of cytokine and glial activation, behavioral and cognitive
      changes, and epigenetic signatures. Identifying distinct neuroimmune states and
      their consequences for neural function will provide a framework for predicting
      vulnerability to disorders of memory, cognition and emotion both during and long
      after recovery from illness.

PMID- 30210312
TI  - Longitudinal Performance of Senescence Accelerated Mouse Prone-Strain 8 (SAMP8)
      Mice in an Olfactory-Visual Water Maze Challenge.
AB  - Morris water maze (MWM) is widely used to assess cognitive deficits in pre
      clinical rodent models. Latency time to reach escape platform is frequently
      reported, but may be confounded by deficits in visual acuity, or differences in
      locomotor activity. This study compared performance of Senescence Accelerated
      Mouse Prone-Strain 8 (SAMP8) and control Senescence Accelerated Mouse Resistant
      Strain 1 (SAMR1) mice in classical MWM, relative to performance in a newly
      developed olfactory-visual maze testing protocol. Performance indicated as the
      escape time to rescue platform for classical MWM testing showed that SAMP8 mice
      as young as 6 weeks of age did poorly relative to age-matched SAMR1 mice. The
      olfactory-visual maze challenge described better discriminated SAMP8 vs. SAMR1
      mice than classical MWM testing, based on latency time measures. Consideration of
      the distance traveled rather than latency time in the classical MWM found no
      treatment effects between SAMP8 and SAMR1 at 40 weeks of age and the olfactory
      visual measures of performance confirmed the classical MWM findings. Longitudinal
      (repeat) assessment of SAMP8 and SAMR1 performance at 6, 20, 30, and 40 weeks of
      age in the olfactory-visual testing protocol showed no age-associated deficits in
      SAMP8 mice to the last age end-point indicated. Collectively, the results from
      this study suggest the olfactory-visual testing protocol may be advantageous
      compared to classical MWM as it avoids potential confounders of visual impairment
      in some strains of mice and indeed, may offer insight into cognitive and
      behavioral deficits that develop with advanced age in the widely used SAMP8
      murine model.

PMID- 30210313
TI  - A Novel Role for the Periaqueductal Gray in Consummatory Behavior.
AB  - The periaqueductal gray (PAG) has a well-established role in pain processing,
      autonomic function and behavioral responses to fear. Anatomical work suggests the
      PAG may mediate food intake and reward processing as it has extensive reciprocal
      connections within brain circuits that mediate appetitive processes and
      consummatory behaviors such as prefrontal cortex, hypothalamus, amygdala,
      parabrachial nucleus (PBN) and ventral tegmental area (Kelley et al., 2005).
      Therefore, we investigated if the PAG of hungry rats has a functional role in
      appetitive and consummatory behaviors. To address this, PAG was pharmacologically
      inactivated during a spatial working memory task with muscimol (0.1-0.3 MUg), a
      GABAA agonist via intracranial infusion. Inactivation of PAG led to reduced
      intake of food rewards and increased errors on this task. To focus on the
      specific effects PAG inactivation had on food consumption, PAG was inactivated
      during two separate food intake tasks in a separate group of rats. Again, PAG
      inactivation resulted in a significant decrease in food consumption, as well as
      an increased latency to consume food. We next investigated PAG neural responses
      to reward encounters. A different group of rats performed the same task used in
      Experiment 1 while the in vivo activity of PAG neurons was recorded. In a subset
      of PAG neurons, reward encounters elicited phasic excitation. A separate subset
      of PAG neurons were inhibited during reward encounters. These responses scaled
      with the size of the reward, with sustained excitation or inhibition in response
      to large rewards compared to small. Our data also show that separate groups of
      PAG neurons in awake behaving animals display either increased and decreased
      neural responses to reward encounters. Additionally, a proportion of neurons were
      modulated by the animals' velocity. This study is the first to show that PAG
      neurons process reward-related information, perhaps to mediate consummatory
      behaviors related to food consumption.

PMID- 30210314
TI  - Non-motor Behavioral Alterations of PGC-1alpha-Deficient Mice - A Peculiar
      Phenotype With Slight Male Preponderance and No Apparent Progression.
AB  - Dysfunction of peroxisome proliferator-activated receptor gamma coactivator
      1alpha (PGC-1alpha) has been linked to various neurodegenerative and
      neuropsychiatric disorders; however, reports on psychic behavioral alterations on
      PGC-1alpha-deficient animals are sparse. The present study revisited prior
      observations of anxiety-related, depression-related, and hippocampal memory
      related observations having been made on different PGC-1alpha-deficient murine
      strains, in a large-scale analysis on whole-body full-length (FL-)PGC-1alpha
      deficient mice. The examinations were performed on animals covering a wide age
      range enrolled from both sexes, and included paradigms such as the open-field,
      elevated plus maze, light-dark box, tail suspension test, and spatial recognition
      two-trial Y-maze. The findings revealed no signs of previously reported anxiety
      like behavior, but revealed an unexpected phenotype with decreased anxiety
      behavior consistent throughout different paradigms, with slight male
      preponderance. This was associated with despair-like anhedonic behavior,
      consistent with that reported previously, but did not associate with either
      peripheral or brain alterations in kynurenic acid synthesis, which was previously
      proposed. Though male FL-PGC-1alpha-deficient mice tended to perform poorer in
      the hippocampus-based spatial learning paradigm, the genotype overall was not
      associated with impairment in spatial memory, contradicting with prior
      observations. None of the observed alterations deteriorated with age, similarly
      to motor alterations as reported previously. The most likely contributors of this
      peculiar phenotype are discussed, with clinicopathological correlations drawn.
      Being the first to address these behavioral domains within the same PGC-1alpha
      deficient strain, our findings extend the knowledge about the complex in vivo
      effect of PGC-1alpha dysfunction and add important notes to research in the field
      of PGC-1alpha in connection with neuropsychiatric disorders.

PMID- 30210311
TI  - Alterations of Coherent Theta and Gamma Network Oscillations as an Early
      Biomarker of Temporal Lobe Epilepsy and Alzheimer's Disease.
AB  - Alzheimer's disease (AD) and temporal lobe epilepsy (TLE) are the most common
      forms of neurodegenerative disorders characterized by the loss of cells and
      progressive irreversible alteration of cognitive functions, such as attention and
      memory. AD may be an important cause of epilepsy in the elderly. Early diagnosis
      of diseases is very important for their successful treatment. Many efforts have
      been done for defining new biomarkers of these diseases. Significant advances
      have been made in the searching of some AD and TLE reliable biomarkers, including
      cerebrospinal fluid and plasma measurements and glucose positron emission
      tomography. However, there is a great need for the biomarkers that would reflect
      changes of brain activity within few milliseconds to obtain information about
      cognitive disturbances. Successful early detection of AD and TLE requires
      specific biomarkers capable of distinguishing individuals with the progressing
      disease from ones with other pathologies that affect cognition. In this article,
      we review recent evidence suggesting that magnetoencephalographic recordings and
      coherent analysis coupled with behavioral evaluation can be a promising approach
      to an early detection of AD and TLE. Highlights -Data reviewed include the
      results of clinical and experimental studies.-Theta and gamma rhythms are
      disturbed in epilepsy and AD.-Common and different behavioral and oscillatory
      features of pathologies are compared.-Coherent analysis can be useful for an
      early diagnostics of diseases.

PMID- 30210316
TI  - Do Individual Differences Influence Moment-by-Moment Reports of Emotion Perceived
      in Music and Speech Prosody?
AB  - Comparison of emotion perception in music and prosody has the potential to
      contribute to an understanding of their speculated shared evolutionary origin.
      Previous research suggests shared sensitivity to and processing of music and
      speech, but less is known about how emotion perception in the auditory domain
      might be influenced by individual differences. Personality, emotional
      intelligence, gender, musical training and age exert some influence on discrete,
      summative judgments of perceived emotion in music and speech stimuli. However,
      music and speech are temporal phenomena, and little is known about whether
      individual differences influence moment-by-moment perception of emotion in these
      domains. A behavioral study collected two main types of data: continuous ratings
      of perceived emotion while listening to extracts of music and speech, using a
      computer interface which modeled emotion on two dimensions (arousal and valence),
      and demographic information including measures of personality (TIPI) and
      emotional intelligence (TEIQue-SF). Functional analysis of variance on the time
      series data revealed a small number of statistically significant differences
      associated with Emotional Stability, Agreeableness, musical training and age. The
      results indicate that individual differences exert limited influence on
      continuous judgments of dynamic, naturalistic expressions. We suggest that this
      reflects a reliance on acoustic cues to emotion in moment-by-moment judgments of
      perceived emotions and is further evidence of the shared sensitivity to and
      processing of music and speech.

PMID- 30210315
TI  - Paternal Care Impacts Oxytocin Expression in California Mouse Offspring and Basal
      Testosterone in Female, but Not Male Pups.
AB  - Natural variations in parenting are associated with differences in expression of
      several hormones and neuropeptides which may mediate lasting effects on offspring
      development, like regulation of stress reactivity and social behavior. Using the
      bi-parental California mouse, we have demonstrated that parenting and aggression
      are programmed, at least in part, by paternal behavior as adult offspring model
      the degree of parental behavior received in development and are more territorial
      following high as compared to low levels of care. Development of these behaviors
      may be driven by transient increases in testosterone following paternal
      retrievals and increased adult arginine vasopressin (AVP) immunoreactivity within
      the bed nucleus of the stria terminalis (BNST) among high-care (HC) offspring. It
      remains unclear, however, whether other neuropeptides, such as oxytocin (OT),
      which is sensitive to gonadal steroids, are similarly impacted by father
      offspring interactions. To test this question, we manipulated paternal care (high
      and low care) and examined differences in adult offspring OT-immunoreactive (OT
      ir) within social brain areas as well as basal T and corticosterone (Cort)
      levels. HC offspring had more OT-ir within the paraventricular nucleus (PVN) and
      supraoptic nucleus (SON) than low-care (LC) offspring. Additionally, T levels
      were higher among HC than LC females, but no differences were found in males.
      There were no differences in Cort indicating that our brief father-pup
      separations likely had no consequences on stress reactivity. Together with our
      previous work, our data suggest that social behavior may be programmed by
      paternal care through lasting influences on the neuroendocrine system.

PMID- 30210317
TI  - Optogenetic Stimulation of GABAergic Neurons in the Globus Pallidus Produces
      Hyperkinesia.
AB  - The globus pallidus (GP) is emerging as a critical locus of basal ganglia control
      of motor activity, but the exact role of GABAergic GP neurons remain to be
      defined. By targeted expression of channelrhodopsin 2 (ChR2) in GABAergic neurons
      using the VGAT-ChR2-EYFP transgenic mice, we showed that optogenetic stimulation
      of GABAergic neurons in the right GP produced hyperkinesia. Optogenetic
      stimulation of GABAergic GP neurons increased c-Fos-positive cells in GP, M1
      cortex, and caudate-putamen (CPu), and decreased c-Fos-positive cells in
      entopeduncular nucleus (EPN), compared to the contralateral hemisphere. In
      agreement with the canonical basal ganglia model. Furthermore, we delivered AAV
      CaMKIIalpha-ChR2-mCherry virus to the excitatory neurons of the subthalamic
      nucleus (STN) and selectively stimulated glutamatergic afferent fibers from the
      STN onto the GP. This optogenetic stimulation produced abnormal movements,
      similar to the behaviors that observed in the VGAT-ChR2-EYFP transgenic mice.
      Meanwhile, we found that the c-Fos expression pattern in the GP, M1, STN, EPN,
      and CPu produced by optogenetic activation of glutamatergic afferent fibers from
      the STN in GP was similar to the c-Fos expression pattern in the VGAT-ChR2-EYFP
      transgenic mice. Taken together, our results suggest that excess GP GABAergic
      neurons activity could be the neural substrate of abnormal involuntary movements
      in hyperkinetic movement disorders. The neural circuitry underlying the abnormal
      involuntary movements is associated with excessive GP, M1, CPu activity, and
      reduced EPN activity. Inhibition of GP GABAergic neurons represents new treatment
      targets for hyperkinetic movement disorder.

PMID- 30210319
TI  - It's Tea Time: Interference of Ayahuasca Brew on Discriminative Learning in
      Zebrafish.
AB  - Ayahuasca is a psychoactive brew traditionally used in shamanistic and
      vegetalistic rituals and has recently received lot of attention due to potential
      cognitive benefits. Ayahuasca effects are caused by the synergistic interaction
      of beta-carbolines (harmine, harmaline and tetrahydroarmine) contained in
      Banisteriopsis caapi stalks combined with the N,N-dimethyltryptamine (DMT) from
      Psychotria viridis leaves, a potent agonist to serotonin (5-HT) receptors. The
      present study approaches the effects of chronic and acute exposure to two
      Ayahuasca concentrations (0.1 and 0.5 ml/L) on the cognitive ability to
      discriminate objects in a one-trial learning task in zebrafish. Based on the
      combination of concentrations and exposure regimens, we divided adult zebrafish
      in five treatment groups: acute 0.1 and 0.5 ml/L, chronic 0.1 and 0.5 ml/L, and
      control 0.0 (n = 20 for each group). Then we tested them in a memory task of
      object discrimination. Acute Ayahuasca exposed groups performed similarly to the
      control group, however chronically treated fish (13 days) presented both impaired
      discriminative performance and locomotor alterations. Overall, these results
      indicate that Ayahuasca is a potent psychoactive drug that, in chronic exposure,
      negatively affects mnemonic parameters in zebrafish. In single exposure it does
      not affects cognitive performance, but the higher concentration (0.5) affected
      locomotion. Moreover, we reinforce the importance of the zebrafish for behavioral
      pharmacological studies of drug screening, in special to psychedelic drug
      research.

PMID- 30210320
TI  - Learning Distinct Chemical Labels of Nestmates in Ants.
AB  - Colony coherence is essential for eusocial insects because it supports the
      inclusive fitness of colony members. Ants quickly and reliably recognize who
      belongs to the colony (nestmates) and who is an outsider (non-nestmates) based on
      chemical recognition cues (cuticular hydrocarbons: CHCs) which as a whole
      constitute a chemical label. The process of nestmate recognition often is
      described as matching a neural template with the label. In this study, we tested
      the prevailing view that ants use commonalities in the colony odor that are
      present in the CHC profile of all individuals of a colony or whether different
      CHC profiles are learned independently. We created and manipulated sub-colonies
      by adding one or two different hydrocarbons that were not present in the original
      colony odor of our Camponotus floridanus colony and later tested workers of the
      sub-colonies in one-on-one encounters for aggressive responses. We found that
      workers adjust their nestmate recognition by learning novel, manipulated CHC
      profiles, but still accept workers with the previous CHC profile. Workers from a
      sub-colony with two additional components showed aggression against workers with
      only one of the two components added to their CHC profile. Thus, additional
      components as well as the lack of a component can alter a label as "non
      nestmate." Our results suggest that ants have multiple-templates to recognize
      nestmates carrying distinct labels. This finding is in contrast to what
      previously has been proposed, i.e., a widening of the acceptance range of one
      template. We conclude that nestmate recognition in ants is a partitioned
      (multiple-template) process of the olfactory system that allows discrimination
      and categorization of nestmates by differences in their CHC profiles. Our
      findings have strong implications for our understanding of the underlying
      mechanisms of colony coherence and task allocation because they illustrate the
      importance of individual experience and task associated differences in the CHC
      profiles that can be instructive for the organization of insect societies.

PMID- 30210318
TI  - Current Status on the Functional Characterization of Chemosensory Receptors of
      Cydia pomonella (Lepidoptera: Tortricidae).
AB  - Cydia pomonella (Lepidoptera: Tortricidae) is a major pest of apple, pear and
      walnuts. For its control, alternative strategies targeting the olfactory system,
      like mating disruption, have been combined with insecticide applications. The
      efficacy of these strategies headed the direction of efforts for the functional
      characterization of codling moth chemosensory receptors to implement further
      control methods based on chemical sensing. With the advent of transcriptomic
      analysis, partial and full-length coding sequences of chemosensory receptors have
      been identified in antennal transcriptomes of C. pomonella. Extension of partial
      coding sequences to full-length by polymerase chain reaction (PCR)-based
      techniques and heterologous expression in empty neurons of Drosophila
      melanogaster and in Human Embryonic Kidney cells allowed functional studies to
      investigate receptor activation and ligand binding modalities (deorphanization).
      Among different classes of antennal receptors, several odorant receptors of C.
      pomonella (CpomORs) have been characterized as binding kairomones (CpomOR3),
      pheromones (CpomOR6a) and compounds emitted by non-host plants (CpomOR19).
      Physiological and pharmacological studies of these receptors demonstrated their
      ionotropic properties, by forming functional channels with the co-receptor
      subunit of CpomOrco. Further investigations reported a novel insect transient
      receptor potential (TRPA5) expressed in antennae and other body parts of C.
      pomonella as a complex pattern of ribonucleic acid (RNA) splice-forms, with a
      possible involvement in sensing chemical stimuli and temperature. Investigation
      on chemosensory mechanisms in the codling moth has practical outcomes for the
      development of control strategies and it inspired novel trends to control this
      pest by integrating alternative methods to interfere with insect chemosensory
      communication.

PMID- 30210324
TI  - Statistical Learning Impairments as a Consequence of Stroke.
AB  - Statistical learning is the implicit learning of the contingencies between
      sequential stimuli, typically from mere exposure. It is present from infancy
      onward, and plays a role in functions from language learning to selective
      attention. Despite these observations, there are few data on whether statistical
      learning capacity changes with age or after brain injury. In order to examine how
      brain injury affects the ability to learn and update statistical representations,
      we had young control and healthy elder participants, as well as participants with
      either left or right brain injury, perform an auditory statistical learning task.
      Participants listened to two languages with made-up words that were defined by
      the transition probability between syllables. Following passive listening,
      learning was assessed with a two-alternative forced choice test for the most
      familiar word. As in previous studies, we found that young controls have a
      learning capacity limitation for statistical learning; a second language is less
      well learned than the first, and this statistical learning capacity limit is
      attenuated with age. Additionally, we found that brain damaged patients, whether
      with left or right hemispheric damage, showed impaired statistical learning. This
      impairment was not explained by aphasia or cognitive deficits. As statistical
      learning is a critical skill for daily life, a better appreciation of the nature
      of this impairment will improve our understanding of the cognitive effects of
      brain injury and could lead to new rehabilitation strategies.

PMID- 30210322
TI  - Neurophysiological Measures of the Perception of Antismoking Public Service
      Announcements Among Young Population.
AB  - Tobacco constitutes a global emergency with totally preventable millions of
      deaths per year and smoking-related illnesses. Public service announcements
      (PSAs) are the main tool against smoking and by now their efficacy is still
      assessed through questionnaires and metrics, only months after their circulation.
      The present study focused on the young population, because at higher risk of
      developing tobacco addiction, investigating the reaction to the vision of
      Effective, Ineffective and Awarded antismoking PSAs through:
      electroencephalography (EEG), autonomic activity variation (Galvanic skin
      response-GSR- and Heart Rate-HR-) and Eye-Tracking (ET). The employed indices
      were: the EEG frontal alpha band asymmetry and the frontal theta; the Emotional
      Index (EI), deriving from the GSR and HR signals matching; the ET Visual
      Attention (VA) index, based on the ratio between the total time spent fixating an
      area of interest (AOI) and its area. Smokers expressed higher frontal alpha
      asymmetry values in comparison to non-smokers. Concerning frontal theta, Awarded
      PSAs reported the highest values in comparison to both Effective and Ineffective
      PSAs. EI results highlighted that lowest values were expressed by Heavy Smokers
      (HS), and Effective PSAs obtained the highest EI values. Finally, concerning the
      Effective PSAs, regression analysis highlighted a correlation between the number
      of cigarettes smoked by participants (independent variable) and frontal alpha
      asymmetry, frontal theta and EI values. ET results suggested that for the
      Ineffective PSAs the main focus were texts, while for the Effective and Awarded
      PSAs were the visual elements. Results support the use of methods aimed at
      assessing the physiological reaction for the evaluation of PSAs images, in
      particular when considering the smoking habits of target populations.

PMID- 30210323
TI  - The 100 Most Cited Papers Concerning the Insular Cortex of the Brain: A
      Bibliometric Analysis.
AB  - Background: The insula is one of the most researched brain regions with many
      highly cited papers. However, unlike the literature of other fields, there is
      currently no study that has identified the 100 most cited papers within the
      literature of the insula. The aim of the current study was to fill in the
      knowledge gap by determining which publications concerning the insula have been
      cited most often, who contributed to them, and what topics they were dealing
      with. Methods: The Web of Science online database was searched to identify the
      100 most cited publications mentioning the insular cortex in their titles,
      abstracts or keywords. To systematically exclude irrelevant publications, the
      search strategy was finalized as: TS = (insula OR insular OR "island of Reil")
      NOT TS = ("insular biogeography" OR "insular mammal*" OR "*insular lymphatic*")
      NOT WC = ("Geochemistry and Geophysics" OR "Ecology"). The identified
      publications were sorted in descending order of citation count. The 100 most
      cited publications concerning the insula of the brain were identified and their
      bibliometric data was extracted and assessed. The VOSviewer software was used
      with default parameters to generate a bubble map that analyzes and visualizes the
      words/phrases used in the titles and abstracts of the publications. Results:
      There were 67 articles on experiments/lab studies and 33 meta-analyses/reviews
      but no opinion or methods paper. They had an average of 943.4 citations (or 62.9
      citations per year), 93.5 references and 13.4 pages. There were 35 papers
      published in open access. USA was the major contributing country. The most top
      ranked publications were concerning emotion, salience and pain. Conclusion: Two
      thirds of the publications concerned the normal brain function/mechanism (n =
      67), whereas 20 publications concerned disease/therapeutic intervention and
      another 13 concerned normal anatomy. For the 67 original articles, 57 used human
      subjects whereas 10 used animal models. MRI was the commonest modality (n = 37),
      followed by PET (n = 16). Nine articles investigated by histology, two by
      multiple modalities and three by other modality.

PMID- 30210321
TI  - Neurobiological Aspects of Face Recognition: The Role of Oxytocin.
AB  - Face recognition is an important index in the formation of social cognition and
      neurodevelopment in humans. Changes in face perception and memory are connected
      with altered sociability, which is a symptom of numerous brain conditions
      including autism spectrum disorder (ASD). Various brain regions and neuropeptides
      are implicated in face processing. The neuropeptide oxytocin (OT) plays an
      important role in various social behaviors, including face and emotion
      recognition. Nasal OT administration is a promising new therapy that can address
      social cognition deficits in individuals with ASD. New instrumental
      neurotechnologies enable the assessment of brain region activation during
      specific social tasks and therapies, and can characterize the involvement of
      genes and peptides in impaired neurodevelopment. The present review sought to
      discuss some of the mechanisms of the face distinguishing process, the ability of
      OT to modulate social cognition, as well as new perspectives and technologies for
      research and rehabilitation of face recognition.

PMID- 30210325
TI  - EEG Microstate Sequences From Different Clustering Algorithms Are Information
      Theoretically Invariant.
AB  - We analyse statistical and information-theoretical properties of EEG microstate
      sequences, as seen through the lens of five different clustering algorithms.
      Microstate sequences are computed for n = 20 resting state EEG recordings during
      wakeful rest. The input for all clustering algorithms is the set of EEG
      topographic maps obtained at local maxima of the spatial variance. This data set
      is processed by two classical microstate clustering algorithms (1) atomize and
      agglomerate hierarchical clustering (AAHC) and (2) a modified K-means algorithm,
      as well as by (3) K-medoids, (4) principal component analysis (PCA) and (5) fast
      independent component analysis (Fast-ICA). Using this technique, EEG topographies
      can be substituted with microstate labels by competitive fitting based on spatial
      correlation, resulting in a symbolic, non-metric time series, the microstate
      sequence. Microstate topographies and symbolic time series are further analyzed
      statistically, including static and dynamic properties. Static properties, which
      do not contain information about temporal dependencies of the microstate sequence
      include the maximum similarity of microstate maps within and between the tested
      clustering algorithms, the global explained variance and the Shannon entropy of
      the microstate sequences. Dynamic properties are sensitive to temporal
      correlations between the symbols and include the mixing time of the microstate
      transition matrix, the entropy rate of the microstate sequences and the location
      of the first local maximum of the autoinformation function. We also test the
      Markov property of microstate sequences, the time stationarity of the transition
      matrix and detect periodicities by means of time-lagged mutual information.
      Finally, possible long-range correlations of microstate sequences are assessed
      via Hurst exponent estimation. We find that while static properties partially
      reflect properties of the clustering algorithms, information-theoretical
      quantities are largely invariant with respect to the clustering method used. As
      each clustering algorithm has its own profile of computational speed, ease of
      implementation, determinism vs. stochasticity and theoretical underpinnings, our
      results convey a positive message concerning the free choice of method and the
      comparability of results obtained from different algorithms. The invariance of
      these quantities implies that the tested properties are algorithm-independent,
      inherent features of resting state EEG derived microstate sequences.

PMID- 30210326
TI  - Gender-Dependent Changes in Time Production Following Quadrato Motor Training in
      Dyslexic and Normal Readers.
AB  - Time estimation is an important component of the ability to organize and plan
      sequences of actions as well as cognitive functions, both of which are known to
      be altered in dyslexia. While attention deficits are accompanied by short Time
      Productions (TPs), expert meditators have been reported to produce longer
      durations, and this seems to be related to their increased attentional resources.
      In the current study, we examined the effects of a month of Quadrato Motor
      Training (QMT), which is a structured sensorimotor training program that involves
      sequencing of motor responses based on verbal commands, on TP using a pre-post
      design. QMT has previously been found to enhance attention and EEG oscillatory
      activity, especially within the alpha range. For the current study, 29 adult
      Hebrew readers were recruited, of whom 10 dyslexic participants performed the
      QMT. The normal readers were randomly assigned to QMT (n = 9) or Verbal Training
      (VT, identical cognitive training with no overt motor component, and only verbal
      response, n = 10). Our results demonstrate that in contrast to the controls,
      longer TP in females was found following 1 month of intensive QMT in the dyslexic
      group, while the opposite trend occurred in control females. We suggest that this
      longer TP in the female dyslexics is related to their enhanced attention
      resulting from QMT. The current findings suggest that the combination of motor
      and mindful training, embedded in QMT, has a differential effect depending on
      gender and whether one is dyslexic or not. These results have implications for
      educational and contemplative neuroscience, emphasizing the connection between
      specifically-structured motor training, time estimation and attention.

PMID- 30210327
TI  - Decentralized Analysis of Brain Imaging Data: Voxel-Based Morphometry and Dynamic
      Functional Network Connectivity.
AB  - In the field of neuroimaging, there is a growing interest in developing
      collaborative frameworks that enable researchers to address challenging questions
      about the human brain by leveraging data across multiple sites all over the
      world. Additionally, efforts are also being directed at developing algorithms
      that enable collaborative analysis and feature learning from multiple sites
      without requiring the often large data to be centrally located. In this paper, we
      propose two new decentralized algorithms: (1) A decentralized regression
      algorithm for performing a voxel-based morphometry analysis on structural
      magnetic resonance imaging (MRI) data and, (2) A decentralized dynamic functional
      network connectivity algorithm which includes decentralized group ICA and sliding
      window analysis of functional MRI data. We compare results against those obtained
      from their pooled (or centralized) counterparts on the same data i.e., as if they
      are at one site. Results produced by the decentralized algorithms are similar to
      the pooled-case and showcase the potential of performing multi-voxel and
      multivariate analyses of data located at multiple sites. Such approaches enable
      many more collaborative and comparative analysis in the context of large-scale
      neuroimaging studies.

PMID- 30210328
TI  - A New Noise-Tolerant Obstacle Avoidance Scheme for Motion Planning of Redundant
      Robot Manipulators.
AB  - Avoiding obstacle(s) is a challenging issue in the research of redundant robot
      manipulators. In addition, noise from truncation, rounding, and model uncertainty
      is an important factor that affects greatly the obstacle avoidance scheme. In
      this paper, based on the neural dynamics design formula, a new scheme with the
      pseudoinverse-type formulation is proposed for obstacle avoidance of redundant
      robot manipulators in a noisy environment. Such a scheme has the capability of
      suppressing constant and bounded time-varying noises, and it is thus termed as
      the noise-tolerant obstacle avoidance (NTOA) scheme in this paper. Theoretical
      results are also given to show the excellent property of the proposed NTOA scheme
      (particularly in noise situation). Based on a PA10 robot manipulator with point
      and window-shaped obstacles, computer simulation results are presented to further
      substantiate the efficacy and superiority of the proposed NTOA scheme for motion
      planning of redundant robot manipulators.

PMID- 30210330
TI  - The McGill Transgenic Rat Model of Alzheimer's Disease Displays Cognitive and
      Motor Impairments, Changes in Anxiety and Social Behavior, and Altered Circadian
      Activity.
AB  - The McGill-R-Thy1-APP transgenic rat is an animal model of the familial form of
      Alzheimer's disease (AD). This model mirrors several neuropathological hallmarks
      of the disease, including the accumulation of beta-amyloid and the formation of
      amyloid plaques (in homozygous animals only), neuroinflammation and the gradual
      deterioration of cognitive functions even prior to plaque formation, although it
      lacks the tauopathy observed in human victims of AD. The goal of the present
      study was a thorough characterization of the homozygous model with emphasis on
      its face validity in several domains of behavior known to be affected in AD
      patients, including cognitive functions, motor coordination, emotionality,
      sociability, and circadian activity patterns. On the behavioral level, we found
      normal locomotor activity in spontaneous exploration, but problems with balance
      and gait coordination, increased anxiety and severely impaired spatial cognition
      in 4-7 month old homozygous animals. The profile of social behavior and
      ultrasonic communication was altered in the McGill rats, without a general social
      withdrawal. McGill rats also exhibited changes in circadian profile, with a
      shorter free-running period and increased total activity during the subjective
      night, without signs of sleep disturbances during the inactive phase. Expression
      of circadian clock gene Bmal1 was found to be increased in the parietal cortex
      and cerebellum, while Nr1d1 expression was not changed. The clock-controlled gene
      Prok2 expression was found to be elevated in the parietal cortex and hippocampus,
      which might have contributed to the observed changes in circadian phenotype. We
      conclude that the phenotype in the McGill rat model is not restricted to the
      cognitive domain, but also includes gait problems, changes in emotionality,
      social behavior, and circadian profiles. Our findings show that the model should
      be useful for the development of new therapeutic approaches targeting not only
      memory decline but also other symptoms decreasing the quality of life of AD
      patients.

PMID- 30210332
TI  - Hydrogen Sulfide Ameliorates Blood-Spinal Cord Barrier Disruption and Improves
      Functional Recovery by Inhibiting Endoplasmic Reticulum Stress-Dependent
      Autophagy.
AB  - Spinal cord injury (SCI) induces the disruption of blood-spinal cord barrier
      (BSCB), which elicits neurological deficits by triggering secondary injuries.
      Hydrogen sulfide (H2S) is a gaseous mediator that has been reported to have
      neuroprotective effect in the central nervous system. However, the relationship
      between H2S and BSCB disruption during SCI remains unknown. Therefore, it is
      interesting to evaluate whether the administration of NaHS, a H2S donor, can
      protect BSCB integrity against SCI and investigate the potential mechanisms
      underlying it. In present study, we found that SCI markedly activated endoplasmic
      reticulum (ER) stress and autophagy in a rat model of complete crushing injury to
      the spinal cord at T9 level. NaHS treatment prevented the loss of tight junction
      (TJ) and adherens junction (AJ) proteins both in vivo and in vitro. However, the
      protective effect of NaHS on BSCB restoration was significantly reduced by an ER
      stress activator (tunicamycin, TM) and an autophagy activator (rapamycin, Rapa).
      Moreover, SCI-induced autophagy was remarkably blocked by the ER stress inhibitor
      (4-phenylbutyric acid, 4-PBA). But the autophagy inhibitor (3-Methyladenine, 3
      MA) only inhibited autophagy without obvious effects on ER stress. Finally, we
      had revealed that NaHS significantly alleviated BSCB permeability and improved
      functional recovery after SCI, and these effects were markedly reversed by TM and
      Rapa. In conclusion, our present study has demonstrated that NaHS treatment is
      beneficial for SCI recovery, indicating that H2S treatment is a potential
      therapeutic strategy for promoting SCI recovery.

PMID- 30210331
TI  - Gene Expression Analysis Reveals Novel Gene Signatures Between Young and Old
      Adults in Human Prefrontal Cortex.
AB  - Human neurons function over an entire lifetime, yet the molecular mechanisms
      which perform their functions and protecting against neurodegenerative disease
      during aging are still elusive. Here, we conducted a systematic study on the
      human brain aging by using the weighted gene correlation network analysis (WGCNA)
      method to identify meaningful modules or representative biomarkers for human
      brain aging. Significantly, 19 distinct gene modules were detected based on the
      dataset GSE53890; among them, six modules related to the feature of brain aging
      were highly preserved in diverse independent datasets. Interestingly, network
      feature analysis confirmed that the blue modules demonstrated a remarkably
      correlation with human brain aging progress. Besides, the top hub genes including
      PPP3CB, CAMSAP1, ACTR3B, and GNG3 were identified and characterized by high
      connectivity, module membership, or gene significance in the blue module.
      Furthermore, these genes were validated in mice of different ages. Mechanically,
      the potential regulators of blue module were investigated. These findings
      highlight an important role of the blue module and its affiliated genes in the
      control of normal brain aging, which may lead to potential therapeutic
      interventions for brain aging by targeting the hub genes.

PMID- 30210329
TI  - Plasticity of Spine Structure: Local Signaling, Translation and Cytoskeletal
      Reorganization.
AB  - Dendritic spines are small protrusive structures on dendritic surfaces, and
      function as postsynaptic compartments for excitatory synapses. Plasticity of
      spine structure is associated with many forms of long-term neuronal plasticity,
      learning and memory. Inside these small dendritic compartments, biochemical
      states and protein-protein interactions are dynamically modulated by synaptic
      activity, leading to the regulation of protein synthesis and reorganization of
      cytoskeletal architecture. This in turn causes plasticity of structure and
      function of the spine. Technical advances in monitoring molecular behaviors in
      single dendritic spines have revealed that each signaling pathway is differently
      regulated across multiple spatiotemporal domains. The spatial pattern of
      signaling activity expands from a single spine to the nearby dendritic area,
      dendritic branch and the nucleus, regulating different cellular events at each
      spatial scale. Temporally, biochemical events are typically triggered by short
      Ca2+ pulses (~10-100 ms). However, these signals can then trigger activation of
      downstream protein cascades that can last from milliseconds to hours. Recent
      imaging studies provide many insights into the biochemical processes governing
      signaling events of molecular assemblies at different spatial localizations.
      Here, we highlight recent findings of signaling dynamics during synaptic
      plasticity and discuss their roles in long-term structural plasticity of
      dendritic spines.

PMID- 30210333
TI  - Discovery and Identification of Pyrazolopyramidine Analogs as Novel Potent
      Androgen Receptor Antagonists.
AB  - Androgen receptor (AR), an important target in the current androgen derivation
      therapy, plays a critical role in the development and progress of prostate cancer
      (PCa). Nonsteroidal antiandrogens, such as enzalutamide and bicalutamide, are
      commonly used in clinic to treat PCa. Though they are very effective at the
      beginning, drug resistance problem appears after about 18 months. One of the
      reasons is that these antiandrogens share similar structure skeleton. Therefore,
      it is urgent to discover novel antiandrogens with different skeletons for
      resistance problem. Herein, we combined structure- and ligand-based methodologies
      for virtual screening chemical databases to identify potent AR antagonists. Then
      the cytotoxic activities of the screened hit samples were evaluated by using
      LNCaP prostate cancer cells. Virtual screening and biological evaluation assay
      results suggest that several chemicals with novel pyrazolopyrimidine skeleton can
      inhibit the proliferation of prostate cancer cells with similar, or even higher,
      bioactivities to bicalutamide. AR reporter gene assay experiments proved that
      Compound III showed potential antagonistic effects. In addition, molecular
      dynamics simulations results proved that Compound III can properly bind to AR and
      prevent helix 12 (H12) from closing to distort the formation of activation
      function 2 (AF2) site, resulting in the invalid transcription. Hence,
      pyrazolopyrimidine was discovered as a novel, potent and promising antiandrogen
      skeleton deserved to be further studied.

PMID- 30210336
TI  - Pharmacokinetics of Nuciferine and N-Nornuciferine, Two Major Alkaloids From
      Nelumbo nucifera Leaves, in Rat Plasma and the Brain.
AB  - The leaf of the lotus (Nelumbo nucifera) is a natural plant resource used as both
      food and herbal medicine (He-Ye) in China. Alkaloids are considered the major
      bioactive compound of the herb and exhibit various biological activities,
      including anti-hyperlipidemia, anti-obesity, anti-inflammatory, and anti
      hyperuricemic effects. Nuciferine (NF) and N-nuciferine (N-NF) are two major
      alkaloids found in the herb. In the present work, the plasma and brain
      pharmacokinetics of the two compounds were investigated after oral and
      intravenous (i.v.) administration of a lotus leaf alkaloid fraction to SD rats
      via ultra-performance liquid chromatography coupled with photodiode array
      detection and brain microdialysis. After oral administration (50 mg/kg), the two
      compounds NF and N-NF were rapidly absorbed into the blood and reached a mean
      maximum concentration (Cmax) of 1.71 MUg/mL at 0.9 h and 0.57 MUg/mL at 1.65 h,
      respectively. After i.v. administration (10 mg/kg), NF and N-NF were found to
      have a relatively wide volume of distribution (Vd, lambdaz, 9.48 and 15.17 L/kg,
      respectively) and slow elimination half-life (t1/2, lambdaz, 2.09 and 3.84 h,
      respectively). The oral bioavailability of NF and N-NF was estimated as 58.13%
      and 79.91%, respectively. After i.v. dosing (20 mg/kg), the two compounds rapidly
      crossed the blood-brain barrier and reached their Cmax (in unbound form): 0.32
      and 0.16 MUg/mL at 0.89 and 1.22 h, respectively. Both alkaloids had widespread
      distribution in the brain, with Vd, lambdaz/F-values of 19.78 L/kg and 16.17
      L/kg, respectively. The mean t1/2, lambdaz values of NF and N-NF in the brain
      were 1.24 and 1.39 h, respectively. These results can help us to better
      understand the characteristics and neuro-pharmacological effects of the lotus
      alkaloid fraction.

PMID- 30210337
TI  - Patient-Reported Symptom Relief Following Medical Cannabis Consumption.
AB  - Background: The Releaf AppTM mobile software application (app) data was used to
      measure self-reported effectiveness and side effects of medical cannabis used
      under naturalistic conditions. Methods: Between 5/03/2016 and 12/16/2017, 2,830
      Releaf AppTM users completed 13,638 individual sessions self-administering
      medical cannabis and indicated their primary health symptom severity rating on an
      11-point (0-10) visual analog scale in real-time prior to and following cannabis
      consumption, along with experienced side effects. Results: Releaf AppTM
      responders used cannabis to treat myriad health symptoms, the most frequent
      relating to pain, anxiety, and depressive conditions. Significant symptom
      severity reductions were reported for all the symptom categories, with mean
      reductions between 2.8 and 4.6 points (ds ranged from 1.29-2.39, ps < 0.001). On
      average, higher pre-dosing symptom levels were associated with greater reported
      symptom relief, and users treating anxiety or depression-related symptoms
      reported significantly more relief (ps < 0.001) than users with pain symptoms. Of
      the 42 possible side effects, users were more likely to indicate and showed a
      stronger correlation between symptom relief and experiences of positive (94% of
      sessions) or a context-specific side effects (76%), whereas negative side effects
      (60%) were associated with lessened, yet still significant symptom relief and
      were more common among patients treating a depressive symptom relative to
      patients treating anxiety and pain-related conditions. Conclusion: Patient
      managed cannabis use is associated with clinically significant improvements in
      self-reported symptom relief for treating a wide range of health conditions,
      along with frequent positive and negative side effects.

PMID- 30210335
TI  - Cornus mas and Cornus Officinalis-Analogies and Differences of Two Medicinal
      Plants Traditionally Used.
AB  - Among 65 species belonging to the genus Cornus only two, Cornus mas L. and Cornus
      officinalis Sieb. et Zucc. (Cornaceae), have been traditionally used since
      ancient times. Cornus mas (cornelian cherry) is native to southern Europe and
      southwest Asia, whereas C. officinalis (Asiatic dogwood, cornel dogwood) is a
      deciduous tree distributed in eastern Asia, mainly in China, as well as Korea and
      Japan. Based on the different geographic distribution of the closely related
      species but clearly distinct taxa, the ethnopharmacological use of C. mas and C.
      officinalis seems to be independently originated. Many reports on the quality of
      C. mas fruits were performed due to their value as edible fruits, and few reports
      compared their physicochemical properties with other edible fruits. However, the
      detailed phytochemical profiles of C. mas and C. officinalis, in particular
      fruits, have never been compared. The aim of this review was highlighting the
      similarities and differences of phytochemicals found in fruits of C. mas and C.
      officinalis in relation to their biological effects as well as compare the
      therapeutic use of fruits from both traditional species. The fruits of C. mas and
      C. officinalis are characterized by the presence of secondary metabolites, in
      particular iridoids, anthocyanins, phenolic acids and flavonoids. However, much
      more not widely known iridoids, such as morroniside, as well as tannins were
      detected particularly in fruits of C. officinalis. The referred studies of
      biological activity of both species indicate their antidiabetic and
      hepatoprotective properties. Based on the available reports antihyperlipidemic
      and anticoagulant activity seems to be unique for extracts of C. mas fruits,
      whereas antiosteoporotic and immunomodulatory activities were assigned to
      preparations of C. officinalis fruits. In conclusion, the comparison of
      phytochemical composition of fruits from both species revealed a wide range of
      similarities as well as some constituents unique for cornelian cherry or Asiatic
      dogwood. Thus, these phytochemicals are considered the important factor
      determining the biological activity and justifying the use of C. mas and C.
      officinalis in the traditional European and Asiatic medicine.

PMID- 30210334
TI  - Suppression of Presymptomatic Oxidative Stress and Inflammation in
      Neurodegeneration by Grape-Derived Polyphenols.
AB  - Neurodegenerative disorders constitute a group of multifaceted conditions
      characterized by the progressive loss of neurons and synaptic connections
      consequent to a combination of specific genetic predispositions and stochastic
      stressors. The neuropathologies observed in both Alzheimer's and Parkinson's
      disease are in part attributed to compounding intrinsic and extrinsic
      environmental stressors, which we propose may be limited by the administration of
      specific grape derived phytochemicals and their metabolized derivatives,
      specifically polyphenols isolated from grape botanicals. Current therapies for
      neurodegenerative disorders are limited as they solely target the final disease
      pathologies including behavioral changes, cognitive deficits, proteinopathies and
      neuronal loss; however, this strategy is not a sustainable approach toward
      managing disease onset or progression. This review discusses the application of
      grape derived polyphenols as an adjunctive treatment paradigm for the prevention
      of neuropathologies associated with Alzheimer's disease, Parkinson's disease and
      Chronic Traumatic Encephalopathy by simultaneously ameliorating two stochastic
      stressors that facilitate their disease pathologies: inflammation and oxidative
      stress. The biophysical attributes of grape-derived polyphenols buffer against
      redox potential dependent peripheral and neuroinflammation and down regulate the
      activation of inflammasomes in microglia and astrocytes, which could provide a
      novel mechanism through which grape-derived polyphenols simultaneously suppress
      risk factors across pathologically distinct neurodegenerative conditions. This
      approach therefore offers a prophylactic mode, not feasible through current
      pharmacological agents, to target activity dependent risk factors for
      neurodegenerative disorders that manifest over an individual's lifetime.

PMID- 30210339
TI  - Integrating Targeted and Untargeted Metabolomics to Investigate the Processing
      Chemistry of Polygoni Multiflori Radix.
AB  - Polygoni Multiflori Radix (PMR, Heshouwu in Chinese), derived from the tuberous
      roots of Polygonum multiflorum Thunb., is a widely-used Chinese medicinal
      material. For traditional clinical use, raw PMR (RPMR) is processed by nine
      cycles of steaming and drying to generate processed PMR (PPMR); RPMR and PPMR
      have distinct medicinal purposes based on the theory of traditional Chinese
      medicine. While PMR has been processed for hundreds of years, including the
      present, the chemistry of that processing has not been well studied. In this
      study, targeted and untargeted metabolomics analyses using ultra-performance
      liquid chromatography-quadrupole/time-of-flight mass spectrometry (UPLC-QTOF
      MS/MS) and ultra-performance liquid chromatography-quadrupole/triple quadrupole
      mass spectrometry (UPLC-QqQ-MS/MS) were integrated to investigate the processing
      chemistry of PMR. The results demonstrate that processing by nine cycles of
      steaming and drying qualitatively and quantitatively alters the chemical profile
      of PMR. Several mechanisms, namely hydrolysis, dehydration, isomerization, and
      Maillard reaction appear to be involved in the chemical transformation that
      occurs. The qualitative and quantitative data further suggest that nine cycles
      might be necessary for the preparation of PPMR, as PPMR that has been processed
      nine times shows significant differences in its chemical profile.

PMID- 30210338
TI  - Survival Benefit of Three Different Therapies in Postoperative Patients With
      Advanced Gastric Cancer: A Network Meta-Analysis.
AB  - Purpose: Gastric cancer is mainly treated by gastrectomy, the results of which
      were unsatisfactory without any adjuvant treatments. This study aimed to examine
      the performance of radiotherapy, chemotherapy, and chemoradiotherapy after
      surgery in order to acquire the optimal adjuvant treatment. Method: Embase and
      PubMed were retrieved to conduct a systematic research. Hazard ratios (HR) of
      overall survival (OS) and progression-free survival (PFS) as outcomes were
      calculated by synthesizing direct and indirect evidence to evaluate the efficacy
      of three treatments against surgery alone. The P-score ranking was utilized to
      rank the therapies. Consistency was assessed by heat plot. Begg's test was
      performed to evaluate publication bias. Results: A total of 35 randomized
      controlled studies (RCTs) with 8973 patients were included in our network meta
      analysis (NMA). As for efficacy outcomes, OS and PFS of 1, 2, 3, and 5 years, all
      revealed chemoradiotherapy (CRT) as the best of three adjuvant therapies.
      Meanwhile, P-score ranking results also displayed that CRT was the optimal
      regimen. Additionally, radiotherapy (RT) and chemotherapy (CT) were two
      alternative options following CRT since RT performed well in short-term survival
      while CT could improve the long-term survival. Conclusion: CRT was the most
      recommended therapy to accompany surgery according to our results. However, no
      analysis about the safety of these three treatments was mentioned in our study.
      Further studies including safety outcomes were required to draw a more
      comprehensive conclusion.

PMID- 30210341
TI  - Prediction of Antitubercular Peptides From Sequence Information Using Ensemble
      Classifier and Hybrid Features.
AB  - Tuberculosis is one of the leading cause of death worldwide, particularly due to
      evolution of drug resistant strains. Antitubercular peptides may provide an
      alternate approach to combat antibiotic tolerance. Sequence analysis reveals that
      certain residues (e.g., Lysine, Arginine, Leucine, Tryptophan) are more prevalent
      in antitubercular peptides. This study describes the models developed for
      predicting antitubercular peptides by using sequence features of the peptides. We
      have developed support vector machine based models using different sequence
      features like amino acid composition, binary profile of terminus residues,
      dipeptide composition. Our ensemble classifiers that combines models based on
      amino acid composition and N5C5 binary pattern, achieves highest Acc of 73.20%
      with 0.80 AUROC on our main dataset. Similarly, the ensemble classifier achieved
      maximum Acc 75.62% with 0.83 AUROC on secondary dataset. Beside this, hybrid
      model achieves Acc of 75.87 and 78.54% with 0.83 and 0.86 AUROC on main and
      secondary dataset, respectively. In order to facilitate scientific community in
      designing of antitubercular peptides, we implement above models in a user
      friendly webserver (http://webs.iiitd.edu.in/raghava/antitbpred/).

PMID- 30210340
TI  - Modular Nanotransporters for Nuclear-Targeted Delivery of Auger Electron
      Emitters.
AB  - This review describes artificial modular nanotransporters (MNTs) delivering their
      cargos into target cells and then into the nuclei - the most vulnerable cell
      compartment for most anticancer agents and especially for radionuclides emitting
      short-range particles. The MNT strategy uses natural subcellular transport
      processes inherent in practically all cells including cancer cells. The MNTs use
      these processes just as a passenger who purchased tickets for a multiple-transfer
      trip making use of different kinds of public transport to reach the desired
      destination. The MNTs are fusion polypeptides consisting of several parts,
      replaceable modules, accomplishing binding to a specific receptor on the cell and
      subsequent internalization, endosomal escape and transport into the cell nucleus.
      Radionuclides emitting short-range particles, like Auger electron emitters,
      acquire cell specificity and significantly higher cytotoxicity both in vitro and
      in vivo when delivered by the MNTs into the nuclei of cancer cells. MNT modules
      are interchangeable, allowing replacement of receptor recognition modules, which
      permits their use for different types of cancer cells and, as a cocktail of
      several MNTs, for targeting several tumor-specific molecules for personalized
      medicine.

PMID- 30210342
TI  - Sanhuang Xiexin Tang Ameliorates Type 2 Diabetic Rats via Modulation of the
      Metabolic Profiles and NF-kappaB/PI-3K/Akt Signaling Pathways.
AB  - Sanhuang Xiexin Tang (SXT), a classic prescription, has been clinically used to
      cure diabetes for thousands of years, but its mechanism remains unclear. Here, a
      systematic in-depth research was performed to unravel how it worked by the
      signaling pathway and metabonomics analysis. Our studies were conducted using
      high-fat diets (HFD) and streptozocin (STZ)-induced type 2 diabetes mellitus
      (T2DM) rats. The blood glucose was measured by a glucose-meter. Protein contents
      were determined by western blotting or ELISA and mRNA expression was identified
      by RT-PCR analysis. The pathological status of pancreas was assessed by
      histopathological analysis. Furthermore, Ultra Performance Liquid Chromatography
      Quadrupole-Time of Flight/Mass Spectrometry (UPLC-Q-TOF/MS) coupled with
      multivariate statistical analysis was performed to discover potential biomarkers
      and the associated pathways. Hyperglycaemia, insulin resistance, dyslipidemia and
      inflammation in T2DM rats were significantly ameliorated after 7-week oral
      administration of SXT. The expressions of phosphatidylinositol-3-kinase (PI-3K),
      protein kinase B (Akt), glucose transporters-4 (GLUT4) Mrna, and p-PI-3K, p-Akt,
      GLUT4 protein involved in the PI-3K/Akt signaling pathway of T2DM were markedly
      up-regulated. Further investigation indicated that the perturbance of metabolic
      profiling in T2DM rats was obviously reversed by SXT and 38 potential biomarkers
      were screened and identified. Our study might help clarify the mechanism of SXT
      and provide some evidences for its clinical application in the future.

PMID- 30210344
TI  - Tibetan Medical Formula Shi-Wei-Gan-Ning-Pill Protects Against Carbon
      Tetrachloride-Induced Liver Fibrosis - An NMR-Based Metabolic Profiling.
AB  - Liver fibrosis is a severe health problem, threatening the life quality and
      causing death, raising great concerns worldwide. Shi-Wei-Gan-Ning-Pill (SWGNP) is
      a traditional Tibetan recipe used to treat hepatic injuries; however, its
      hepatoprotective mechanism has not yet fully clarified. In this study,
      histological staining, biochemical assays, and elements determination were
      applied to evaluate the anti-fibrotic efficacy of SWGNP on a carbon tetrachloride
      (CCl4) induced hepato-fibrosis rat model. NMR-based metabolomics combined with
      orthogonal partial least squares-discriminant analysis (OPLS-DA), canonical
      regression analysis, and correlation networks analysis was used to characterize
      the potential biomarkers as well as metabolic pathways associated with the
      hepatoprotective activity of SWGNP. The results showed that SWGNP could
      significantly attenuate the pathological changes and decrease the levels of
      fibrosis markers (ColIV, HA, LN, and PCIII), and regulate the disordered elements
      distribution. Multivariate analysis and correlation network analysis revealed
      that SWGNP could protect rats against CCl4-induced liver fibrosis through anti
      oxidation, repairing the impaired energy metabolisms and reversing the disturbed
      amino acids and nucleic acids metabolisms. In conclusion, this integrated
      metabolomics approach provided new insights into the mechanism of the
      hepatoprotective effect of SWGNP in liver fibrosis disease.

PMID- 30210343
TI  - Screening Pregnant Women and Their Neonates for Illicit Drug Use: Consideration
      of the Integrated Technical, Medical, Ethical, Legal, and Social Issues.
AB  - North America is currently suffering from one of the worst epidemics of illicit
      drug use in recent history: the opioid crisis. Pregnant women are not immune to
      the ravages of substance misuse which affects themselves, their pregnancies, and
      the wider community. The prevalence of drug misuse in pregnancy is not well
      quantified due to the lack of good validated tests, cooperation between
      clinicians and scientists developing tests, and consensus as to who should be
      tested and how results should be used. A wide range of tissues can be tested for
      drug use, including maternal blood, urine, and hair; neonatal meconium, urine,
      and hair; and placenta and umbilical cord tissues. Testing methods range from
      simple spectrophotometry and clinical chemistry to sophisticated analytical HPLC
      or mass spectrometry techniques. The drive for ever greater accuracy and
      sensitivity must be balanced with the necessities of medical practice requiring
      minimally invasive sampling, rapid turnaround, and techniques that can be
      realistically utilized in a clinical laboratory. Better screening tests have
      great potential to improve neonatal and maternal medical outcomes by enhancing
      the speed and accuracy of diagnosis. They also have great promise for public
      health monitoring, policy development, and resource allocation. However, women
      can and have been arrested for positive drug screens with even preliminary
      results used to remove children from custody, before rigorous confirmatory
      testing is completed. Balancing the scientific, medical, public health, legal,
      and ethical aspects of screening tests for drugs in pregnancy is critical for
      helping to address this crisis at all levels.

PMID- 30210345
TI  - Cyclocarya paliurus Leaves Tea Improves Dyslipidemia in Diabetic Mice: A
      Lipidomics-Based Network Pharmacology Study.
AB  - Hyperlipidemia and hepatic steatosis afflict over 75% of patients with type 2
      diabetes, causing diabetic dyslipidemia. Cyclocarya paliurus (CP) leaf is a
      herbal tea which has long been consumed by the Chinese population, particularly
      people suffering from obesity and diabetes. CP appears to exhibit a hypolipidemic
      effect in lipid loaded mice (Kurihara et al., 2003), although the detailed
      mechanisms and active ingredients for this hypolipidemic effect have not yet been
      answered. In this study, we investigated the beneficial effects of CP and
      predicted the mechanisms by utilizing lipidomics, serum-pharmacochemistry and
      network pharmacology approaches. Our results revealed that serum and hepatic
      levels of total triglyceride (TG), total cholesterol (T-CHO), low-density
      lipoproteins (LDL) and high-density lipoproteins (HDL), as well as 30 lipids
      including cholesterol ester (CE), diglyceride (DG), phosphatidylethanolamine
      (PE), phosphatidylcholine (PC), and sphingomyelin (SM) in CP-treated mice were
      improved in comparison with untreated diabetic mice. In parallel, 14
      phytochemical compounds of CP were determined in mice serum after CP
      administration. Mechanistically, the network pharmacology analysis revealed the
      predicted targets of CP's active ingredients ALOX12, APP, BCL2, CYP2C9, PTPN1 and
      linked lipidome targets PLD2, PLA2G(s), and PI3K(s) families could be responsible
      for the CP effects on diabetic dyslipidemia. In conclusion, this study revealed
      the beneficial effects of CP on diabetic dyslipidemia are achieved by reducing
      accumulation of hepatic lipid droplets and regulating circulatory lipids in
      diabetic mice, possibly through PI3K signaling and MAPK signaling pathways.
      GRAPHICAL ABSTRACTWork flow of the evaluation of the effects and mechanisms of
      Cyclocarya paliurus leaves tea on dyslipidemia in diabetic mice.

PMID- 30210346
TI  - Pioglitazone, a PPAR-gamma Activator, Stimulates BKCa but Suppresses IK M in
      Hippocampal Neurons.
AB  - Pioglitazone (PIO), a thiazolidinedone, was reported to stimulate peroxisome
      proliferator-activated receptor-gamma (PPAR-gamma) with anti-inflammatory, anti
      proliferative, anti-diabetic, and antidepressive activities. However, whether
      this compound exerts any perturbations on Ca2+-activated K+ and M-type K+
      currents in central neurons remains largely unresolved. In this study, we
      investigated the effects of PIO on these potassium currents in hippocampal
      neurons (mHippoE-14). In whole-cell current recordings, the presence of PIO (10
      MUM) increased the amplitude of Ca2+-activated K+ current [IK(Ca)] in mHippoE-14
      cells. PIO-induced stimulation of IK(Ca) observed in these cells was reversed by
      subsequent addition of paxilline, yet not by TRAM-39 or apamin. In inside-out
      current recordings, PIO applied to the bath concentration-dependently increased
      the activity of large-conductance Ca2+-activated K+ (BKCa) channels with an EC50
      value of 7.6 MUM. Its activation of BKCa channels in mHippoE-14 cells was voltage
      dependent and accompanied by both a lengthening in mean open time and a
      shortening in slow component of mean closed time. The activation curve of BKCa
      channels after addition of PIO was shifted to less depolarized potential without
      any change in the gating charge. PIO also suppressed the amplitude of M-type K+
      currents inherently in mHippoE-14 neurons. Taken together, in addition to its
      agonistic action on PPAR-gamma, PIO-induced perturbation of these potassium
      channels may be responsible for its widely pharmacological actions on hippocampal
      neurons.

PMID- 30210347
TI  - Water Soluble Antioxidative Crude Polysaccharide From Russula senecis Elicits TLR
      Modulated NF-kappaB Signaling Pathway and Pro-inflammatory Response in Murine
      Macrophages.
AB  - Russula senecis has recently been reported as a new addition to macrofungal flora
      of West Bengal. Besides, it also emerged as a seasonal health promoting nutrient
      to local ethnic people and enlisted for the first time as tribal food in our
      previous publication. In this context, the present work was designed to establish
      such usefulness scientifically and to meet the aim, crude polysaccharide,
      Rusenan, was prepared using conventional heated water reflux. Initially, the
      polymers were characterized to determine chemical composition and for that
      spectrophotometry along with Fourier-transform infrared spectroscopy (FT-IR),
      high-performance thin-layer chromatography (HPTLC), and gas chromatography-mass
      spectrometry (GC-MS) were performed. Analysis indicated that Rusenan was
      consisted mainly of carbohydrate conjugated with trace amount of protein.
      Furthermore, glucose was detected as the major monosaccharide (mainly in beta
      type glycosidic linkage) while other monomers were presented in the order of
      galactose > mannose > xylose > rhamnose. Conversely, antioxidant potential was
      determined following eight in vitro systems where the fraction evidenced strong
      superoxide, hydroxyl, 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3
      ethylbenzothiazoline-6-sulphonic acid) (ABTS) radical scavenging activity, high
      affinity to Fe2+ as well as instant ability to donate electron with EC50 values
      ranging from 80 to 3885 MUg/ml concentration. In addition, effect on murine
      macrophages was also investigated where the polysaccharide treatment increased
      cell proliferation, phagocytic activity, filopodia or lamellipodia formation,
      nitric oxide (NO) production and reactive oxygen species (ROS) synthesis.
      Thereafter, through reverse transcriptase polymerase chain reaction (RT-PCR)
      analysis, significant increase in the expression of Toll like receptor (TLR)-4,
      TLR-2 and nuclear factor kappa B (NF-kappaB) was observed; as a result alleviated
      level of cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS), tumor
      necrosis factor (TNF)-alpha, IkappaB-alpha, and interferon (IFN)-gamma were also
      noticed explaining definite immune-stimulatory activity of the fraction. Thus,
      overall finding suggests that R. senecis can be considered as a functional food
      and may be used in preparation of dietary supplement to enhance general health.

PMID- 30210348
TI  - Gomisin A Suppresses Colorectal Lung Metastasis by Inducing AMPK/p38-Mediated
      Apoptosis and Decreasing Metastatic Abilities of Colorectal Cancer Cells.
AB  - Gomisin A (G.A) is a dietary lignan compound from Schisandra chinensis. In this
      study, the effect of G.A on the proliferation and metastasis of colorectal cancer
      (CRC) cells was investigated using several CRC cell lines and a lung metastasis
      mouse model. Both oral and intraperitoneal administration of G.A (50 mg/kg)
      inhibited lung metastasis of CT26 cells. Various concentrations of G.A were
      incubated with CRC cell lines and their viability was determined using a cell
      counting kit-8 assay. G.A significantly decreased the viability of various CRC
      cell lines, whereas it did not change the proliferation of normal colon cells.
      G.A induced G0/G1 phase arrest and apoptosis of CT26 and HT29 cells by regulating
      cyclin D1/cyclin-dependent kinase 4 (CDK4) expression and apoptotic proteins such
      as caspases and B-cell lymphoma-2 (Bcl-2) family proteins, respectively. G.A
      induced apoptosis was mediated by AMPK/p38 activation in CRC cells. A non
      cytotoxic concentration of G.A inhibited epithelial-mesenchymal transition of CRC
      cells by modulating E-cadherin and N-cadherin expression levels. Moreover, the
      migration and invasion of CRC cells were reduced by G.A treatment. Especially,
      G.A decreased matrix metalloproteinase (MMP)-2 and MMP-9 expressions and
      activities. G.A ameliorated lung metastasis of CRC cells by decreasing cell
      survival and metastatic abilities of CRC cells. Thus, G.A might be a potential
      novel therapeutic agent for metastatic CRC.

PMID- 30210349
TI  - Pharmacokinetic Behavior of Vincristine and Safety Following Intravenous
      Administration of Vincristine Sulfate Liposome Injection in Chinese Patients With
      Malignant Lymphoma.
AB  - Objective: This phase Ia study was designed to assess the pharmacokinetic (PK)
      characters of free vincristine (F-VCR, refer to as non-liposomal VCR and VCR
      released from liposome) and total vincristine (T-VCR, the sum of both liposomal
      VCR and F-VCR), urinary excretion and safety of intravenous administration of
      vincristine sulfate liposomes injection (VSLI) in Chinese patients with malignant
      lymphoma and compare the results with those for conventional vincristine sulfate
      injection (VSI). Methods: In the phase Ia, randomized, open-label, two sequence
      cross-over study, patients from one group were exposed to treatment 1 including
      cytoxan (cyclophosphamide power injection), hydroxyrubicin (adriamycin power
      injection), oncovin (VSI), and prednisone tablets (standard CHOP scheme) before
      crossed over to treatment 2 (modified CHOP scheme in which VSI was replaced with
      VSLI). Patients from another group received treatments in reverse order. Results:
      In this phase Ia study, a total of eight subjects participated. VCR elimination
      from the circulation after injection of VSLI was characterized by a significantly
      increased maximum concentration (Cmax, 86.6 ng/mL) and plasma area under the
      plasma concentration-time curve from zero to infinity (AUC0-Inf, 222.1 ng/mL h),
      markedly decreased distribution volume (Vz, 224.1 L) and plasma clearance (CL,
      8.9 L/h) compared to lower Cmax (26.6 ng/mL) and AUC0-Inf (95.1 ng/mL h), larger
      Vz (688.8 L) and CL (22.1 L/h) for VSI. The small proportion of F-VCR following
      infusion of VSLI in circulation was reflected by very low Cmax (1.8 ng/mL) and
      AUC0-Inf (50.5 ng/mL h). Less than 3% of the administered dose of VSLI was
      excreted in urine and the extent was similar to that for VSI. The elimination
      percentage of 40-21-14% for VSI changed to 6.2-24-39% for VSLI at intervals of 0
      5, 5-13 and 13-25 h, respectively. Significant difference of toxicity between
      VSLI and VSI was not observed. Conclusion: VSLI exhibits higher AUC0-Inf of T
      VCR, lower CL and Vz compared with VSI. VSLI was well tolerated, maybe due to the
      markedly decreasing AUC0-Inf of F-VCR. The majority of VCR was enveloped in
      liposome and VCR was released gradually from liposome following injection of
      VSLI. Liposomal encapsulation of VCR does not alter the route and extent of VCR
      excretion in urine.

PMID- 30210351
TI  - Transcriptomics and Fitness Data Reveal Adaptive Plasticity of Thermal Tolerance
      in Oysters Inhabiting Different Tidal Zones.
AB  - Fine-scale adaptive evolution is always constrained by strong gene flow at
      vertical level in marine organisms. Rapid environmental fluctuations and
      phenotypic plasticity through optimization of fitness-related traits in organisms
      play important roles in shaping intraspecific divergence. The coastal systems
      experience strong variations in multiple abiotic environmental factors,
      especially the temperature. We used a typical intertidal species, Pacific oyster
      (Crassostrea gigas), to investigate the interaction between plasticity and
      adaptive evolution. We collected intertidal and subtidal oysters from two
      ecological niches and carried out common garden experiments for one generation.
      We identified fine-scale vertical adaptive divergence between intertidal and
      subtidal F1 progeny at both sites, based on different hierarchical phenotypes,
      including morphological, physiological, and molecular traits. We further
      quantified the global plasticity to thermal stress through transcriptomic
      analysis. The intertidal oysters exhibited slow growth rate. However, they showed
      high survival and metabolic rates under heat stress, indicating vertically fine
      scale phenotypic adaptive mechanisms and evolutionary trade-offs between growth
      and thermal tolerance. Transcriptomic analysis confirmed that the intertidal
      oysters have evolved high plasticity. The genes were classified into three types:
      evolutionarily divergent, concordantly plastic, and adaptive plastic genes. The
      evolved divergence between intertidal and subtidal oysters for these gene sets
      showed a significant positive correlation with plastic changes of subtidal
      populations in response to high temperature. Furthermore, the intertidal oysters
      exhibited delayed large-scale increase in expressional plasticity than that in
      subtidal counterparts. The same direction between plasticity and selection
      suggests that the oysters have evolved adaptive plasticity. This implies that
      adaptive plasticity facilitates the oyster to adapt to severe intertidal zones.
      The oysters exposed to strong environmental variability are thermal tolerant and
      have high adaptive potential to face the current global warming. Our findings
      will not only provide new insights into the significant role of plasticity in
      adaptive evolution that can be extended to other marine invertebrates, but also
      provide basic information for oyster resources conservation and reef
      reestablishment.

PMID- 30210350
TI  - Triptriolide Alleviates Lipopolysaccharide-Induced Liver Injury by Nrf2 and NF
      kappaB Signaling Pathways.
AB  - Nrf2 (Nuclear Factor Erythroid 2 Related Factor 2) transcription factor not only
      regulates oxidative stress response, but also represses inflammation by
      regulating cytokines production and cross-talking with NF-kappaB signaling
      pathways. Nrf2 plays an essential role in liver injury induced by oxidative
      stress and inflammation. Triptriolide (T11) is a minor component of Tripterygium
      wilfordii Hook F. (TwHF), which can be obtained by hydrolysis reaction of
      triptolide (T9). The major purpose of this study is to clarify the regulating
      effects of T11 on oxidative stress and inflammation in vivo and in vitro. LPS
      stimulated RAW 264.7 cells were used to verify the regulating effects of T11 on
      oxidative stress (ROS and Nrf2 signaling pathway) and inflammatory cytokines
      production (TNF-alpha, IL-6 and IL-1beta). The antioxidant responsive element
      (ARE) luciferase assay was employed to evaluate Nrf2 activation effect of T11 in
      HEK-293T cells. Lipopolysaccharides (LPS) induced acute liver injury (ALI) in
      BALB/c mice were used to study the protective effects (ALT, AST, MDA, SOD,
      histopathology and neutrophils/macrophages filtration) and the underlying
      protection mechanisms of ALI amelioration (Nrf2 and NF-kappaB signaling pathway)
      of T11. Firstly, the results showed that T11 can not only effectively decrease
      the productions of inflammatory cytokines (TNF-alpha, IL-6 and IL-1beta), ROS and
      NO in LPS-stimulated RAW 264.7 cells, but also further significantly increase the
      activity of Nrf2 in HEK-293T cells. Secondly, the results suggested that T11
      could dramatically decrease the oxidative stress responses (SOD and MDA) and
      inflammation (histopathology, neutrophils/macrophages filtration, TNF-alpha, IL-6
      and IL-1beta production) in LPS-induced ALI in BALB/c mice. Finally, the results
      implied that T11 could dramatically increase Nrf2 protein expression and decrease
      p-TAK1, p-IkappaBalpha and NF-kappaB protein expression both in vivo and in
      vitro. In conclusion, our findings indicated that T11 could alleviate LPS induced
      oxidative stress and inflammation by regulating Nrf2 and NF-kappaB signaling
      pathways in vitro and in vivo, which offers a novel insights for the application
      of TwHF in clinical.

PMID- 30210352
TI  - Metabolomics Study of the Biochemical Changes in the Plasma of Myocardial
      Infarction Patients.
AB  - Myocardial infarction (MI) is a common and multifactorial disease that has the
      highest morbidity and mortality in the world. Although a number of physiological,
      pathological, and functional parameters have been investigated, only scarce
      information regarding the changes of small metabolites in the plasma has been
      reported, and this lack of information may cause poor MI diagnosis and treatment.
      In the present study, we aimed to investigate the metabolic profiles of plasma
      samples from MI patients to identify potential disease biomarkers and to study
      the pathology of MI. Metabolic profiles of the plasma of 30 MI patients and 30
      controls were obtained using ultra-performance liquid chromatography/electrospray
      ionization quadruple time-of-flight mass spectrometry. The resulting data were
      processed using pattern recognition approaches, including principal component
      analysis and partial least squares-discriminant analysis, to identify the
      metabolites that differed between the groups. Significant differences in the
      plasma levels of the following 10 metabolites were observed in the MI patients
      compared with the controls: phosphatidylserine, C16-sphingosine, N-methyl
      arachidonic amide, N-(2-methoxyethyl) arachidonic amide,
      linoleamidoglycerophosphate choline, lyso-PC (C18:2), lyso-PC (C16:0), lyso-PC
      (C18:1), arachidonic acid, and linoleic acid. The changes in these 10 biomarkers
      indicated perturbations of energy metabolism, phospholipid metabolism, and fatty
      acid metabolism in the MI patients. These findings hold promise to advance the
      treatment, diagnosis, and prevention of MI.

PMID- 30210353
TI  - Morphometric Reconstruction of Coronary Vasculature Incorporating Uniformity of
      Flow Dispersion.
AB  - Experimental limitations in measurements of coronary flow in the beating heart
      have led to the development of in silico models of reconstructed coronary trees.
      Previous coronary reconstructions relied primarily on anatomical data, including
      statistical morphometry (e.g., diameters, length, connectivity, longitudinal
      position). Such reconstructions are non-unique, however, often leading to
      unrealistic predicted flow features. Thus, it is necessary to impose
      physiological flow constraints to ensure realistic tree reconstruction. Since a
      vessel flow depends on its diameter to fourth power, diameters are the logical
      candidates to guide vascular reconstructions to achieve realistic flows. Here, a
      diameter assignment method was developed where each vessel diameter was
      determined depending on its downstream tree size, aimed to reduce flow dispersion
      to within measured range. Since the coronary micro-vessels are responsible for a
      major portion of the flow resistance, the auto regulated coronary flow was
      analyzed in a morphometry-based reconstructed 400 vessel arterial microvascular
      sub-tree spanning vessel orders 1-6. Diameters in this subtree were re-assigned
      based on the flow criteria. The results revealed that diameter re-assignment,
      while adhering to measured morphometry, significantly reduced the flow dispersion
      to realistic levels while adhering to measured morphometry. The resulting network
      flow has longitudinal pressure distribution, flow fractal nature, and near
      neighboring flow autocorrelation, which agree with measured coronary flow
      characteristics. Collectively, these results suggest that a realistic coronary
      tree reconstruction should impose not only morphometric data but also flow
      considerations. The work is of broad significance in providing a novel
      computational framework in the field of coronary microcirculation. It is
      essential for the study of coronary circulation by model simulation, based on a
      realistic network structure.

PMID- 30210357
TI  - Editorial: Tooth Enamel: Frontiers in Mineral Chemistry and Biochemistry,
      Integrative Cell Biology and Genetics.

PMID- 30210355
TI  - Slow Recovery of Excitability Increases Ventricular Fibrillation Risk as
      Identified by Emulation.
AB  - Purpose: Rotor stability and meandering are key mechanisms determining and
      sustaining cardiac fibrillation, with important implications for anti-arrhythmic
      drug development. However, little is yet known on how rotor dynamics are
      modulated by variability in cellular electrophysiology, particularly on kinetic
      properties of ion channel recovery. Methods: We propose a novel emulation
      approach, based on Gaussian process regression augmented with machine learning,
      for data enrichment, automatic detection, classification, and analysis of re
      entrant biomarkers in cardiac tissue. More than 5,000 monodomain simulations of
      long-lasting arrhythmic episodes with Fenton-Karma ionic dynamics, further
      enriched by emulation to 80 million electrophysiological scenarios, were
      conducted to investigate the role of variability in ion channel densities and
      kinetics in modulating rotor-driven arrhythmic behavior. Results: Our methods
      predicted the class of excitation behavior with classification accuracy up to
      96%, and emulation effectively predicted frequency, stability, and spatial
      biomarkers of functional re-entry. We demonstrate that the excitation wavelength
      interpretation of re-entrant behavior hides critical information about rotor
      persistence and devolution into fibrillation. In particular, whereas action
      potential duration directly modulates rotor frequency and meandering, critical
      windows of excitability are identified as the main determinants of breakup.
      Further novel electrophysiological insights of particular relevance for
      ventricular arrhythmias arise from our multivariate analysis, including the role
      of incomplete activation of slow inward currents in mediating tissue rate
      dependence and dispersion of repolarization, and the emergence of slow recovery
      of excitability as a significant promoter of this mechanism of dispersion and
      increased arrhythmic risk. Conclusions: Our results mechanistically explain pro
      arrhythmic effects of class Ic anti-arrhythmics in the ventricles despite their
      established role in the pharmacological management of atrial fibrillation. This
      is mediated by their slow recovery of excitability mode of action, promoting
      incomplete activation of slow inward currents and therefore increased dispersion
      of repolarization, given the larger influence of these currents in modulating the
      action potential in the ventricles compared to the atria. These results exemplify
      the potential of emulation techniques in elucidating novel mechanisms of
      arrhythmia and further application to cardiac electrophysiology.

PMID- 30210354
TI  - A Review of Molecular Responses of Catfish to Bacterial Diseases and Abiotic
      Stresses.
AB  - Catfish is one of the major aquaculture species in the United States. However,
      the catfish industry is threatened by several bacterial diseases such as enteric
      septicemia of catfish (ESC), columnaris disease and Aeromonas disease, as well as
      by abiotic stresses such as high temperature and low oxygen. Research has been
      conducted for several decades to understand the host responses to these diseases
      and abiotic stresses. With the development of sequencing technologies, and the
      application of genome-wide association studies in aquaculture species,
      significant progress has been made. This review article summarizes recent
      progress in understanding the molecular responses of catfish after bacterial
      infection and stress challenges, and in understanding of genomic and genetic
      basis for disease resistance and stress tolerance.

PMID- 30210356
TI  - The Fibrotic Substrate in Persistent Atrial Fibrillation Patients: Comparison
      Between Predictions From Computational Modeling and Measurements From Focal
      Impulse and Rotor Mapping.
AB  - Focal impulse and rotor mapping (FIRM) involves intracardiac detection and
      catheter ablation of re-entrant drivers (RDs), some of which may contribute to
      arrhythmia perpetuation in persistent atrial fibrillation (PsAF). Patient
      specific computational models derived from late gadolinium-enhanced magnetic
      resonance imaging (LGE-MRI) has the potential to non-invasively identify all
      areas of the fibrotic substrate where RDs could potentially be sustained,
      including locations where RDs may not manifest during mapped AF episodes. The
      objective of this study was to carry out multi-modal assessment of the
      arrhythmogenic propensity of the fibrotic substrate in PsAF patients by comparing
      locations of RD-harboring regions found in simulations and detected by FIRM
      (RDsim and RDFIRM) and analyze implications for ablation strategies predicated on
      targeting RDs. For 11 PsAF patients who underwent pre-procedure LGE-MRI and FIRM
      guided ablation, we retrospectively simulated AF in individualized atrial models,
      with geometry and fibrosis distribution reconstructed from pre-ablation LGE-MRI
      scans, and identified RDsim sites. Regions harboring RDsim and RDFIRM were
      compared. RDsim were found in 38 atrial regions (median [inter-quartile range
      (IQR)] = 4 [3; 4] per model). RDFIRM were identified and subsequently ablated in
      24 atrial regions (2 [1; 3] per patient), which was significantly fewer than the
      number of RDsim-harboring regions in corresponding models (p < 0.05).
      Computational modeling predicted RDsim in 20 of 24 (83%) atrial regions
      identified as RDFIRM-harboring during clinical mapping. In a large number of
      cases, we uncovered RDsim-harboring regions in which RDFIRM were never observed
      (18/22 regions that differed between the two modalities; 82%); we termed such
      cases "latent" RDsim sites. During follow-up (230 [180; 326] days), AF recurrence
      occurred in 7/11 (64%) individuals. Interestingly, latent RDsim sites were
      observed in all seven computational models corresponding to patients who
      experienced recurrent AF (2 [2; 2] per patient); in contrast, latent RDsim sites
      were only discovered in two of four patients who were free from AF during follow
      up (0.5 [0; 1.5] per patient; p < 0.05 vs. patients with AF recurrence). We
      conclude that substrate-based ablation based on computational modeling could
      improve outcomes.

PMID- 30210358
TI  - Lipidomics Reveals a Tissue-Specific Fingerprint.
AB  - In biological systems lipids generate membranes and have a key role in cell
      signaling and energy storage. Therefore, there is a wide diversity of molecular
      lipid expressed at the compositional level in cell membranes and organelles, as
      well as in tissues, whose lipid distribution remains unclear. Here, we report a
      mass spectrometry study of lipid abundance across 7 rat tissues, detecting and
      quantifying 652 lipid molecular species from the glycerolipid,
      glycerophospholipid, fatty acyl, sphingolipid, sterol lipid and prenol lipid
      categories. Our results demonstrate that every tissue analyzed presents a
      specific lipid distribution and concentration. Thus, glycerophospholipids are the
      most abundant tissue lipid, they share a similar tissue distribution but differ
      in particular lipid species between tissues. Sphingolipids are more concentrated
      in the renal cortex and sterol lipids can be found mainly in both liver and
      kidney. Both types of white adipose tissue, visceral and subcutaneous, are rich
      in glycerolipids but differing the amount. Acylcarnitines are mainly in the
      skeletal muscle, gluteus and soleus, while heart presents higher levels of
      ubiquinone than other tissues. The present study demonstrates the existence of a
      rat tissue-specific fingerprint.

PMID- 30210359
TI  - Functional Characterization of Odorant Binding Protein 27 (RproOBP27) From
      Rhodnius prolixus Antennae.
AB  - Olfactory proteins mediate a wide range of essential behaviors for insect
      survival. Odorant binding proteins (OBPs) are small soluble olfactory proteins
      involved in the transport of odor molecules (=odorants) through the sensillum
      lymph to odorant receptors, which are housed on the dendritic membrane of
      olfactory sensory neurons also known as olfactory receptor neurons. Thus, a
      better understanding of the role(s) of OBPs from Rhodnius prolixus, one of the
      main vectors of Chagas disease, may ultimately lead to new strategies for vector
      management. Here we aimed at functionally characterize OBPs from R. prolixus.
      Genes of interest were selected using conventional bioinformatics approaches and
      subsequent quantification by qPCR. We screened and estimated expression in
      different tissues of 17 OBPs from R. prolixus adults. These analyses showed that
      11 OBPs were expressed in all tissues, whereas six OBP genes were specific to
      antennae. Two OBP genes, RproOBP6 and RproOBP13, were expressed in both male and
      female antennae thus suggesting that they might be involved in the recognition of
      semiochemicals mediating behaviors common to both sexes, such host finding (for a
      blood meal). Transcripts for RproOBP17 and RproOBP21 were enriched in female
      antennae and possibly involved in the detection of oviposition attractants or
      other semiochemicals mediating female-specific behaviors. By contrast, RproOBP26
      and RproOBP27 might be involved in the reception of sex pheromones given that
      their transcripts were highly expressed in male antennae. To test this
      hypothesis, we silenced RproOBP27 using RNAi and examined the sexual behavior of
      the phenotype. Indeed, adult males treated with dsOBP27 spent significantly less
      time close to females as compared to controls. Additionally, docking analysis
      suggested that RproOBP27 binds to putative sex pheromones. We therefore concluded
      that RproOBP27 might be a pheromone-binding protein.

PMID- 30210360
TI  - Chronic Stress Produces Persistent Increases in Plasma Corticosterone, Reductions
      in Brain and Cardiac Nitric Oxide Production, and Delayed Alterations in
      Endothelial Function in Young Prehypertensive Rats.
AB  - This study was designed to investigate whether oxidative stress, nitric oxide
      (NO) deficiency and/or endothelial dysfunction (ED) are present in young
      borderline hypertensive rats (BHR) and whether these pathologies can be causally
      involved in the initiation of blood pressure (BP) increases. Additionally, we
      tested the hypothesis that crowding stress, experienced during the peripubertal
      period, may produce persistent or delayed disorders in corticosterone release, NO
      synthesis, oxidative status and/or endothelial function that could accelerate BP
      increases. To test these hypotheses, 5-week-old male BHR and normotensive Wistar
      Kyoto rats (WKY) were either kept in control conditions (for 2 and 4 weeks,
      respectively) or exposed to social stress produced by crowding for 2 weeks
      (stress). After cessation of crowding, a group of rats of each phenotype was kept
      in control conditions for the next 2 weeks (post-stress). Systolic BP of 5-week
      old BHR was significantly increased vs. age-matched WKY (127 +/- 3 vs. 104 +/- 3
      mmHg, p < 0.01) and remained significantly higher throughout the course of the
      experiment. Despite elevated BP, no signs of oxidative damage to plasma lipids,
      NO deficiency or ED were observed in control BHR vs. age-matched WKY. Crowding
      stress elevated plasma corticosterone and accelerated BP increases only in BHR;
      these effects persisted 2 weeks post-stress. Crowding failed to induce oxidative
      damage to plasma lipids in either phenotype, but it produced persistent decreases
      in NO production in the hypothalamus and brainstem of both strains of rats, as
      well as in the hearts of BHR. In contrast, crowding failed to reduce NO
      production in the aortae or acetylcholine-induced relaxations of the femoral
      arteries in both strains investigated. However, significantly reduced aortic NO
      production was observed in BHR 2 weeks post-stress vs. age-matched controls,
      which was in agreement with reduced NO-dependent components of vasorelaxation. In
      conclusion, this study's data showed that oxidative stress, NO deficiency and ED
      are not causally involved in initiation of blood pressure increase in BHR.
      However, exposure to stressful environments produced persistent increases in
      plasma corticosterone and reductions of brain and cardiac NO production followed
      by a delayed decrease in the NO-dependent component of endothelium-dependent
      relaxation-changes that collectively accelerated BP increases only in BHR.

PMID- 30210361
TI  - Mosquito Hemocytes Associate With Circulatory Structures That Support
      Intracardiac Retrograde Hemolymph Flow.
AB  - A powerful immune system protects mosquitoes from pathogens and influences their
      ability to transmit disease. The mosquito's immune and circulatory systems are
      functionally integrated, whereby intense immune processes occur in areas of high
      hemolymph flow. The primary circulatory organ of mosquitoes is the dorsal vessel,
      which consists of a thoracic aorta and an abdominal heart. In adults of the
      African malaria mosquito, Anopheles gambiae, the heart periodically alternates
      contraction direction, resulting in intracardiac hemolymph flowing toward the
      head (anterograde) and toward the posterior of the abdomen (retrograde). During
      anterograde contractions, hemolymph enters the dorsal vessel through ostia
      located in abdominal segments 2-7, and exits through an excurrent opening located
      in the head. During retrograde contractions, hemolymph enters the dorsal vessel
      through ostia located at the thoraco-abdominal junction, and exits through
      posterior excurrent openings located in the eighth abdominal segment. The ostia
      in abdominal segments 2 to 7-which function in anterograde intracardiac flow-are
      sites of intense immune activity, as a subset of hemocytes, called periostial
      hemocytes, respond to infection by aggregating, phagocytosing, and killing
      pathogens. Here, we assessed whether hemocytes are present and active at two
      sites important for retrograde intracardiac hemolymph flow: the thoraco-abdominal
      ostia and the posterior excurrent openings of the heart. We detected sessile
      hemocytes around both of these structures, and these hemocytes readily engage in
      phagocytosis. However, they are few in number and a bacterial infection does not
      induce the aggregation of additional hemocytes at these locations. Finally, we
      describe the process of hemocyte attachment and detachment to regions of the
      dorsal vessel involved in intracardiac retrograde flow.

PMID- 30210362
TI  - Skeletal Muscle Insulin Sensitivity Show Circadian Rhythmicity Which Is
      Independent of Exercise Training Status.
AB  - Circadian rhythms can be perturbed by shift work, travel across time zones, many
      occupational tasks, or genetic mutations. Perturbed circadian rhythms are
      associated with the increasing problem of obesity, metabolic dysfunction, and
      insulin resistance. We hypothesized that insulin sensitivity in skeletal muscle
      follows a circadian pattern and that this pattern is important for overall
      metabolic function. This hypothesis was verified using mice as a model system. We
      observed circadian rhythmicity in whole body insulin tolerance, as well as in
      signaling pathways regulating insulin- and exercise-induced glucose uptake in
      skeletal muscle, including AKT, 5'-adenosine monophosphate-activated protein
      kinase (AMPK) and TBC1 domain family member 4 (TBC1D4) phosphorylation. Basal and
      insulin-stimulated glucose uptake in skeletal muscle and adipose tissues in vivo
      also differed between day- and nighttime. However, the rhythmicity of glucose
      uptake differed from the rhythm of whole-body insulin tolerance. These results
      indicate that neither skeletal muscle nor adipose tissue play a major role for
      the circadian rhythmicity in whole-body insulin tolerance. To study the circadian
      pattern of insulin sensitivity directly in skeletal muscle, we determined glucose
      uptake under basal and submaximal insulin-stimulated conditions ex vivo every
      sixth hour. Both insulin sensitivity and signaling of isolated skeletal muscle
      peaked during the dark period. We next examined the effect of exercise training
      on the circadian rhythmicity of insulin sensitivity. As expected, voluntary
      exercise training enhanced glucose uptake in skeletal muscle. Nevertheless,
      exercise training did not affect the circadian rhythmicity of skeletal muscle
      insulin sensitivity. Taken together, our results provide evidence that skeletal
      muscle insulin sensitivity exhibits circadian rhythmicity.

PMID- 30210363
TI  - Postoperative Pain Assessment Indices Based on Photoplethysmography Waveform
      Analysis.
AB  - The purpose of this study was to derive parameters that might reflect
      postoperative pain from photoplethysmography (PPG) and verify the derived
      parameters in postoperative pain assessment. We obtained preoperative and
      postoperative PPG and 100-mm visual analog scale (VAS) from 65 surgical patients
      and extracted a total of 51 PPG morphology-based parameters and their normalized
      parameters from these PPGs obtained. Pain discrimination performances of these
      derived parameters were assessed by statistical analyses, including Wilcoxon
      signed rank test with Bonferroni correction, classification accuracy based on
      logistic regression, and 4-fold cross validation. After comparing these
      parameters derived from PPG in pre- and post-operative conditions, statistically
      significant difference was found in 36 of the 51 parameters. Using logistic
      classification, dynamic between-pulse parameters such as normalized systolic
      amplitude variation and normalized diastolic amplitude variation showed better
      pain classification performance than the static within-pulse parameters. VAS
      score was 0 in every pre-operation condition, but >60 VAS was observed in the
      post-operative condition. Systolic peak amplitude variation normalized by PPG AC
      amplitude showed the best performance in classifying post-operative pain, with
      accuracy, sensitivity, specificity, and positive predictivity values of 79.5,
      74.0, 86.0, and 84.5%, respectively. These results are superior to those of the
      surgical pleth index (SPI, GE Healthcare, Chicago, IL, United States) at 65.9,
      65.9, 66.5, and 66.5%, respectively.

PMID- 30210364
TI  - Effect of Resveratrol on Blood Rheological Properties in LPS-Challenged Rats.
AB  - Objectives: Abnormal rheological properties induce adverse effects during sepsis.
      This study sought to investigate the hypothesis that resveratrol (Res) improves
      blood rheological properties in rats following a lipopolysaccharide (LPS)
      challenge, and provide a novel approach for treatment of sepsis. Methods: The
      rats were intraperitoneally or intramuscularly injected with vehicle, LPS (8
      mg/kg), Res (30 mg/kg), or both to yield four groups: control, Res, LPS, and LPS
      + Res. After 6 h of LPS and/or Res injection, the mean arterial pressure (MAP),
      regional blood flow, erythrocyte and leukocyte parameters, and blood viscosity
      were observed. Results: LPS administration had no significant effects on the
      erythrocyte parameters and plasma viscosity. LPS administration reduced the MAP,
      whole blood viscosity at low and medium shear rates, the blood flow in the spleen
      and kidney, and the leukocyte content in whole blood when compared to control
      group, and increased the myeloperoxidase (MPO) activity in lung. Treatment with
      Res alone had no effects on most of parameters observed except increasing the
      whole blood relative viscosity. However, Res treatment after LPS resulted in
      further decrease in whole blood viscosity at high and medium shear rates.
      Furthermore, Res treatment conversely decreased the red blood cell distribution
      width-CV, blood flow of stomach, whole blood relative viscosity and MPO activity
      in lung, and increased the leukocyte content, but did not restore LPS-induced
      decrease in MAP and the blood flow in the spleen and kidney. Conclusion: The Res
      treatment partly reduce the whole blood viscosity and regional blood flow, and
      increase WBC content in peripheral blood following the LPS challenge, suggesting
      a favorable role in expanding the quasi-sympathetic effects of LPS in blood
      viscosity at early stages.

PMID- 30210365
TI  - Telmisartan Modulates the Oral Mucositis Induced by 5-Fluorouracil in Hamsters.
AB  - Oral mucositis (OM) is a common adverse effect resulting from cancer therapy. The
      OM it has implications that may compromise oncologic treatment and decrease the
      patient's quality of life. The therapeutic options to prevent or treat the
      symptoms of OM are scarce; there is no effective therapy that improves the
      symptoms. Based on the need for further research for the treatment of OM, the
      present study objective was to evaluate the effect of telmisartan (TELM) on the
      OM induced by 5-fluorouracil (5-FU), using as animal model Golden Syrian
      hamsters. 5-FU followed by mechanical trauma on day 4 was used to induce OM in
      hamsters. Euthanasia occurred on the day 10. The experiments were constituted by
      the groups saline, mechanical trauma, 5-FU, and TELM in three doses (1, 5, or 10
      mg/kg). Macroscopic, histopathological, and immunohistochemical analyses as well
      as immunofluorescence experiments were performed on the oral mucosa of the
      animals. The samples also were used for analysis enzyme-linked immunosorbent
      assays and quantitative real-time polymerase chain reactions (qPCR). TELM (5 or
      10 mg/kg) was able to reduce the inflammatory ulceration and infiltration in the
      oral mucosa of the animals, decreasing the levels of the cytokines TNF-alpha and
      IL-1beta. These treatments was minimize the immunostaining for cyclooxygenase-2,
      matrix metalloproteinase-9, transforming growth factor-beta, and smad 2/3. The
      nuclear transcription factor kappa B (NFkappaB) p65 and inducible nitric oxide
      synthase were reduced in the oral mucosa. Finally, TELM (10 mg/kg) increased the
      PPARgamma gene expression and reduced STAT1 and NFkappaB p65 gene expression
      relative to the 5-FU group. Therefore, TELM prevents the OM produced by 5-FU on
      animal model.

PMID- 30210367
TI  - Insomnia Really Hurts: Effect of a Bad Night's Sleep on Pain Increases With
      Insomnia Severity.
AB  - Insomnia and chronic pain are highly prevalent conditions and are often comorbid.
      Somatic complaints other than pain are also often observed in insomnia. Poor
      sleep and pain are known to mutually reinforce each other. However, it is unknown
      whether the habitual severity of insomnia modulates the acute effect of a
      particularly bad night's sleep on the next day's pain severity, and whether it
      modulates the acute effect of pain on the following night's sleep quality. Using
      data from 3,508 volunteers (2,684 female, mean age 50.09 y), we addressed these
      questions in addition to the associations between the habitual severity of
      insomnia, somatic complaints, and pain. Results indicated that people suffering
      from more severe habitual insomnia showed stronger mutual acute within-day
      reactivity of pain and poor sleep quality. The same increased reactivity was
      found in people with more severe habitual pain. Interestingly, the acute within
      day mutual reactivity of pain and sleep quality showed consistent asymmetry. Pain
      worsened more after a particularly bad night's sleep than it improved after a
      particularly good night's sleep. Likewise, sleep worsened more after a day with
      more-than-usual pain than it improved after a day with less-than-usual pain.
      Future interventions may profit from addressing this asymmetric mutual reactivity
      especially in people with severe comorbid insomnia and chronic pain.

PMID- 30210366
TI  - Feeding Stimulation Ability and Central Effects of Intraperitoneal Treatment of L
      Leucine, L-Valine, and L-Proline on Amino Acid Sensing Systems in Rainbow Trout:
      Implication in Food Intake Control.
AB  - To continue gathering knowledge on the central regulation of food intake in
      response to amino acids in teleost fish, using as a model rainbow trout
      (Oncorhynchus mykiss), we evaluated in a first experiment the feeding
      attractiveness of L-leucine, L-valine, and L-proline offered as an agar gel
      matrix. In a second experiment, we assessed the effect of intraperitoneal (IP)
      treatment with the same amino acids on food intake. In a third experiment, we
      carried out a similar IP administration of amino acids to evaluate the response
      of amino acid sensing mechanisms in the hypothalamus and telencephalon. Results
      are discussed in conjunction with an earlier study where leucine and valine were
      administered intracerebroventricularly (ICV). The attractiveness of amino acids
      does not appear to relate to their effects on food intake, at least when
      administrated by-passing ingestion and luminal absorption, since two attractive
      amino acids resulted in an anorexigenic (Leu) or no effects (Pro) on food intake
      while a non-attractive amino acid (Val) induced anorexigenic (IP treatment) or
      orexigenic (ICV treatment) responses. The effects of Leu on food intake might
      relate to the expression of hypothalamic neuropeptides and result from the direct
      activation of amino acid sensing systems. In contrast, while valine had few
      effects on hypothalamic amino acid sensing systems after ICV treatment, a
      significant amount of parameters become affected by IP treatment suggesting that
      the effect of Val after IP treatment is indirect. Proline had no relevant effects
      on amino acid sensing systems, neuropeptide expression, and food intake, which
      suggest that this amino acid might not have a relevant role in the homeostatic
      regulation of food intake through hypothalamic mechanisms. In telencephalon, the
      same amino acid sensing systems operating in hypothalamus appear to be present
      and respond to Leu and Val, but it is still unclear how they might relate to the
      control of food intake.

PMID- 30210369
TI  - Anatomical Templates of the Midbrain Ventral Tegmental Area and Substantia Nigra
      for Asian Populations.
AB  - Increasing evidence shows that the midbrain dopaminergic system is involved in
      various functions. However, details of the role of the midbrain dopaminergic
      system in these functions are still to be determined in humans. Considering that
      the ventral tegmental area (VTA) and substantia nigra (SN) in the midbrain are
      the primary dopamine producers, creating reliable anatomical templates of the VTA
      and SN through neuroimaging studies would be useful for achieving a detailed
      understanding of this dopaminergic system. Although VTA and SN anatomical
      templates have been created, no specific templates exist for the Asian
      population. Thus, we conducted anatomical and resting-state functional magnetic
      resonance imaging (rs-fMRI) studies to create VTA and SN templates for the Asian
      population. First, a neuromelanin-sensitive MRI technique was used to visualize
      the VTA and SN, and then individual hand-drawn VTA and SN regions of interests
      (ROIs) were traced on a small sample of neuromelanin-sensitive MRIs (dataset 1).
      Second, individual hand-drawn VTA and SN ROIs were normalized to create
      normalized VTA and SN templates for the Asian population. Third, a seed-based
      functional connectivity analysis was performed on rs-fMRI data using hand-drawn
      ROIs to calculate neural networks of VTA and SN in dataset 1. Fourth, a seed
      based functional connectivity analysis was performed using VTA and SN seeds that
      were created based on normalized templates from dataset 1. Subsequently, a seed
      based functional connectivity analysis was performed using VTA and SN seeds in
      another, larger sample (dataset 2) to assess whether neural networks of VTA or SN
      seeds from dataset 1 would be replicated in dataset 2. The Asian VTA template was
      smaller and located in a more posterior and inferior part of the midbrain
      compared to the published VTA template, while the Asian SN template, relative to
      the published SN template, did not differ in size but was located in the more
      inferior part of the midbrain. The neural networks of the VTA and SN seeds in
      dataset 1 were replicated in dataset 2. Altogether, our normalized template of
      the VTA and SN could be used for measuring fMRI activities related to the VTA and
      SN in the Asian population.

PMID- 30210368
TI  - A Systematic Review of Cognitive Predictors of Treatment Outcome in Major
      Depression.
AB  - Background: Research suggests that only 50% of patients with major depression
      respond to psychotherapy or pharmacological treatment, and relapse is common.
      Therefore, there is interest in elucidating factors that help predict clinical
      response. Cognitive impairment is a key feature of depression, which often
      persists beyond remission; thus, the aim of this systematic review was to
      determine whether baseline cognitive functioning can predict treatment outcomes
      in individuals with depression. Method: Studies examining cognitive predictors of
      treatment response in depression were identified using Pub Med and Web of Science
      databases. Given the heterogeneity of outcome measures, the variety of treatment
      protocols, and the differing ways in which data was presented and analyzed, a
      narrative rather than meta-analytic review technique was used. Results: 39
      studies met inclusion criteria. Findings in younger adult samples were
      inconclusive. There was some evidence for a predictive effect of executive
      function and to a lesser extent, psychomotor speed, on treatment response. There
      was no evidence of learning or memory being associated with treatment response.
      In older-aged samples, the evidence was much more consistent, suggesting that
      poor executive function predicts poor response to SSRIs. Conclusions: Findings
      from the present review suggest that certain aspects of cognitive functioning,
      particularly executive function, may be useful in predicting treatment response
      in depression. This is certainly the case in elderly samples, with evidence
      suggesting that poor executive functioning predicts poor response to SSRIs. With
      further research, baseline cognitive functioning may serve as a factor which
      helps guide clinical decision making. Moreover, cognitive deficits may become
      targets for specific pharmacological or psychological treatments, with the hope
      of improving overall outcome.

PMID- 30210370
TI  - Cogmed Working Memory Training Presents Unique Implementation Challenges in
      Adults With ADHD.
AB  - Cogmed Working Memory Training (CWMT), an online cognitive training program
      developed for children, is an increasingly popular non-pharmacological
      intervention for ADHD amongst all ages, despite limited supporting evidence. The
      initial objective of the present work was to examine the short- and long-term
      impacts of CWMT on brain function in adults with ADHD. However, during the
      conduct of our study, we experienced multiple levels of failures in recruitment
      and retention that signaled potential concerns about the suitability of CWMT for
      adults with ADHD. This perspective piece aims to describe the difficulties we
      encountered in the context of studies examining the efficacy of CWMT in
      comparable populations. We trace these difficulties to the limited tolerability
      of the current CWMT structure for adults with ADHD, and review similar
      limitations in the literature. We suggest that efficacy of CWMT in children may
      be due in large part to close monitoring and scaffolding provided by clinicians
      and caregivers. For CWMT to have viability for widespread use in adults, greater
      support and structure will be needed for users to improve the likelihood of
      adherence. We discuss implications and considerations for future efforts in both
      research and clinical practice.

PMID- 30210373
TI  - Prevalence of Mental Distress Among Syrian Refugees With Residence Permission in
      Germany: A Registry-Based Study.
AB  - Background: High rates of prevalence of mental distress among the Syrian refugee
      population have been repeatedly confirmed. However, little is known about the
      influence of length of stay, living conditions, and residence permission in the
      host country or about the duration of the escape journey and travel conditions on
      mental health in this refugee population. This study examines the mental health
      of Syrian refugees, taking into account the circumstances in their country of
      origin and host country, as well as their escape conditions. Methods: This
      investigation formed part of a registry-based study. A sample of 518 adult Syrian
      refugees in Erlangen, Germany, who have residence permission was identified. The
      response rate was 38.6%; a total of 200 Syrian refugees thus participated in the
      study. The respondents were investigated for post-traumatic stress disorder
      (ETI), depression (PHQ-9), generalized anxiety (GAD-7) and post-migration
      variables. Results: The prevalence of participants who had personally experienced
      and/or witnessed traumatic events was 75.3%. Symptoms of PTSD were found in 11.4%
      of the participants. Moderate to severe depression was confirmed in 14.5% and
      moderate to severe generalized anxiety in 13.5% of the sample. The criteria for
      at least one diagnosis were met by 30.5% of the participants. More severe PTSD
      symptoms were associated with older age, shorter validity of the residence
      permit, larger number of traumatic events (TEs) and higher generalized anxiety
      symptoms. Depression symptoms were associated with younger age, shorter duration
      of escape journey, larger number of TEs and higher generalized anxiety symptoms.
      Generalized anxiety symptoms correlated with female gender, PTSD, and depression
      symptoms. Conclusions: These findings suggest that Syrian refugees in Germany are
      a vulnerable population, especially if they have experienced and/or witnessed
      multiple traumatic events. However, post-migration conditions and positive future
      prospects in the host country can be protective factors for this population.

PMID- 30210371
TI  - Emotion Transfer, Emotion Regulation, and Empathy-Related Processes in Physician
      Patient Interactions and Their Association With Physician Well-Being: A
      Theoretical Model.
AB  - Physicians experience many emotionally challenging situations in their
      professional lives, influencing their emotional state through emotion contagion
      or social appraisal processes. Successful emotion regulation is crucial to
      sustain health, enable well-being, foster resilience, and prevent burnout or
      compassion fatigue. Despite the alarmingly high rate of stress-related disorders
      in physicians, affecting not only physician well-being, but also outcomes such as
      physician performance, quality of care, or patient satisfaction, research on how
      to deal with emotionally challenging situations in physicians is lacking. Based
      on extant literature, the present article proposes a theoretical model depicting
      emotions, emotion regulation, and empathy-related processes and their relation to
      well-being in provider-client interactions. This model serves as a basis for
      future research and interventions aiming at improving physician well-being and
      professional functioning. As a first step, interviews with 21 psychiatrists were
      conducted. Results of qualitative and initial quantitative analyses provided
      detailed descriptions of the model's components confirming its usefulness for
      detecting mechanisms linking emotion regulation and well-being in psychiatrist
      patient interactions. Additionally, results lend preliminary support for the
      validity of the model, suggesting that successful regulation of emotions (i.e.,
      achieving a desired emotional state) elicited by cyclical transfer processes in
      provider-client interactions is associated with both short- and long-term well
      being and resilience. Furthermore, empathy-related emotions and their regulation
      seem to be linked to well-being. Based on the results of the present study, a
      prospective longitudinal study is under preparation, which is intended to inform
      effective interventions targeting emotion transfer, empathy-related processes,
      and emotion regulation in physicians' professional lives. The model and results
      are also potentially applicable to other health care and social services
      providers.

PMID- 30210374
TI  - Prison Suicide in Comparison to Suicide Events in Forensic Psychiatric Hospitals
      in Germany.
AB  - Background: There is limited international as well as national research on
      suicide events in prisons and in forensic psychiatric hospitals. This
      retrospective study compares completed suicide events within these two high-risk
      populations in state institutions over a time period of 5 years from 2000 to
      2004. Material and Methods: Data was collected through a nationwide survey: all
      forensic psychiatric hospitals within Germany were contacted via postal mail and
      received a questionnaire concerning the suicide events from 2000 to 2004. All
      federal lands of Germany were similarly assessed by a survey endorsed by the
      respective federal ministries of justice. All prison institutions (100%)
      participated in the survey, while 84% (53 units) of the forensic psychiatric
      hospitals nationwide contributed. A comparative statistical analysis was
      conducted using Fisher's exact test or the Mann-Whitney U-test (age). A
      multivariate logistic regression analysis was done to assess adjusted effects.
      For the Kaplan-Meier analysis, the months until suicide were analyzed followed by
      a Cox-regression analysis. Results: There was no statistically significant
      difference between the mean suicide rate in forensic psychiatric hospitals
      (123/100.000, 95% confidence interval: [0.00103, 0.00147]) and in the prison
      system (130/100.000, 95% confidence interval: [0.00109, 0.00154]). Patients who
      committed suicide in the forensic hospitals were, in comparison to the prison
      system, more likely to have committed a violent offense and have had a prior
      history of suicide attempts. The duration from admission into the institution to
      the suicide event was significantly shorter in the prison group. Also, younger
      people commited suicide earlier during their stay in a forensic psychiatric
      hospital or prison. Conclusions: While the results suggest a necessity to
      optimize data collection in the prison system (prior suicide events and history
      of mental disorder), it is important to discuss the current discharge
      arrangements within the forensic hospitals.

PMID- 30210376
TI  - The Typology of V2 and the Distribution of Pleonastic die in the Ghent Dialect.
AB  - The goal of our paper is to provide a description of an apparent V3 pattern which
      is salient with some speakers of the Ghent dialect, illustrated in (1), from
      Vanacker (1980). Vroeger, die bakten wij vier soorten brood     formerly die
      baked  we four sorts    bread     "We used to bake four kinds of bread."
      (Gijzenzele 0.28) (Vanacker, 1980, p. 76) In such examples, what would be an
      initial adverbial constituent in the root clause vroeger, ("formerly") is
      separated from the finite verb by what Vanacker (1980) labels a "pleonastic"
      element, die, in effect leading to a superficial V3 order. At first sight, this
      element die is optional and it has no impact on the truth conditions of the
      proposition that it introduces. (2) is also acceptable in the dialect. (2)
      Vroeger bakten wij vier soorten brood. formerly baked we four sorts    bread "We
      used to bake four kinds of bread." In the first part of the paper, we will
      provide a description of the distribution of die. We will also compare its
      distribution with that of the more widely distributed resumptive adverbs dan
      ("then") and daar ("there"), which are typical of the Germanic V2 languages
      (Salvesen, 2016). Our account will be based both on authentic data drawn from
      corpora and from anecdotal observations as well as on the results of elicitations
      with 10 native speakers of the dialect. In the second part of the paper we
      provide an analysis in terms of Wolfe's (2016) typology of the syntax of V2.
      Adopting the articulated structure of CP as elaborated in the cartographic
      framework, we will propose that die is an overt spell out of the head Force and
      as such a root complementiser.

PMID- 30210372
TI  - Associations Among Suicidal Ideation, White Matter Integrity and Cognitive
      Deficit in First-Episode Schizophrenia.
AB  - Objective: The study was aimed to investigate the possible associations among
      suicidal ideation, brain white matter (WM) integrity and cognitive deficit in
      first-episode schizophrenia (FES) using diffusion tensor imaging. Methods: The
      sample contained 18 FES patients with suicidal ideation (SI+), 45 FES patients
      without suicidal ideation (SI-) and 44 healthy controls. The Calgary Depression
      Scale for Schizophrenia was used to measure the suicidal ideation and depression
      symptoms. The whole brain WM integrity and three domains of cognitive function:
      working memory, verbal comprehension as well as processing speed were compared
      between the three groups. Results: Compared with SI-, SI+ showed preserved WM
      integrity as indicated by significantly higher factional anisotropy (FA) or lower
      mean diffusivity (MD) in multiple WM tracts, and higher FA coupled with lower MD
      in bilateral posterior corona radiata. Compared with SI-, SI+ were more depressed
      and had less cognitive deficit in working memory and verbal comprehension. The
      fiber tracts in bilateral posterior corona radiata connect to the precuneus as
      shown by probabilistic tractography, and their WM integrity disruptions were
      found to be positively associated with the cognitive deficits in the FES
      patients. Discussion: Preserved WM integrity may be a risk factor for suicidal
      ideation in FES patients. One possible explanation is that it contributes to
      preserved cognitive function, especially in working memory and verbal
      comprehension, which may be associated with greater insight and could lead to
      increased depression and suicidal ideation. The posterior corona radiata and the
      precuneus may be linked to the related biological processes.

PMID- 30210375
TI  - A Pro-Inflammatory Diet Is Associated With an Increased Odds of Depression
      Symptoms Among Iranian Female Adolescents: A Cross-Sectional Study.
AB  - Background: The relation between dietary inflammation and risk of depression has
      not been widely explored. We examined the association between the inflammatory
      effect of the diet and the odds of depression among Iranian female adolescents.
      Methods: Using a stratified cluster sampling technique, 300 female adolescents
      aged 15-18 years were recruited from schools in Tehran between years 2014-2015.
      Depression was assessed using the Depression, Anxiety and Stress Scale (DASS)- a
      21-point scale. The dietary inflammatory index (DII(r)) was used to evaluate the
      inflammatory potential of the diet. Dietary intake was assessed using a validated
      food frequency questionnaire. In addition to descriptive statistics,
      multivariable linear and logistic regression were used to calculate confounder
      adjusted beta estimates and odds ratios. Results: In total, 88 females (30%) had
      at least a moderate level of depressive symptoms (DASS > 6). Females with the
      most pro-inflammatory diet had higher DASS depression score (beta = 1.67; 95% CI
      = 0.03, 3.31) and were at 3.96 (95% CI = 1.12, 13.97) times higher odds of having
      at least moderate depressive symptoms, compared to females with the least anti
      inflammatory diets. Conclusion: These data suggest that Iranian adolescent
      females eating a pro-inflammatory diet, as indicated by higher DII scores, had
      greater odds of having at least moderate depressive symptoms.

PMID- 30210377
TI  - Sustained Inattentional Blindness Does Not Always Decrease With Age.
AB  - Children usually miss additional information when they focus on objects or
      events. This common phenomenon is termed as inattentional blindness. To explore
      the age-related degree of this phenomenon, we applied a motion task to study the
      developmental difference of inattentional blindness. A group of 7-to-14-year-old
      children and adults participated in Experiment 1. The results showed that there
      was no significant developmental difference in sustained inattentional blindness.
      Considering that young children's performance on the primary task was poor, we
      hypothesized that the difficulty of the primary task may contribute to the
      negative findings. Therefore, we decreased the difficulty of the primary task in
      Experiment 2. Still, the developmental difference in inattentional blindness
      rates was absent. Overall, current results implied that the ability of a person
      to detect an unexpected moving stimuli does not always increase with age. The age
      related inattentional blindness seems highly dependent on tasks.

PMID- 30210378
TI  - Feedback-Related Electroencephalogram Oscillations of Athletes With High and Low
      Sports Anxiety.
AB  - We investigated the relationship between performance-related anxiety and the
      neural response to error feedback that was delivered during the execution of a
      time estimation task. Using the Sport Anxiety Scale (SAS-2), we selected
      university athletes high and low in sports anxiety. Participants executed a time
      estimation task where they were instructed to estimate 1 s by pressing a button
      after a sound cue. They performed this task while their performance was being
      evaluated by an experimenter (evaluation condition) and also while alone (in a no
      evaluation condition). We tested whether feedback-related brain activities may
      increase in amplitude in the evaluation condition compared to the control
      condition - especially for athletes who report high performance-related anxiety.
      We focused on oscillations of sub-delta, delta, and theta frequency bands phase
      locked to the feedback onset. Time-frequency analyses revealed that the magnitude
      of both the sub-delta component (0.3-1.2 Hz) and the theta component (4-8 Hz)
      were larger in incorrect than correct trials. In addition, the theta component
      was smaller for athletes high in sports anxiety than for athletes low in sports
      anxiety. The delta component was overall larger for correct than incorrect
      feedback. Further, athletes high in sports anxiety exhibited a larger delta
      component (1.5-3.5 Hz) for correct feedback in the evaluation condition than in
      the no-evaluation condition. Our results suggest that evaluation by others may
      increase the delta oscillation associated with correct feedback processing -
      especially among athletes high in sports anxiety.

PMID- 30210379
TI  - The Psychophysiology of Action: A Multidisciplinary Endeavor for Integrating
      Action and Cognition.
AB  - There is a vast amount of literature concerning the integration of action and
      cognition. Although this broad research area is of great interest for many
      disciplines like sports, psychology and cognitive neuroscience, only a few
      attempts tried to bring together different perspectives so far. Our goal is to
      provide a perspective to spark a debate across theoretical borders and
      integration of different disciplines via psychophysiology. In order to boost
      advances in this research field it is not only necessary to become aware of the
      different areas that are relevant but also to consider methodological aspects and
      challenges. We briefly describe the most relevant theoretical accounts to the
      question of how internal and external information processes or factors interact
      and, based on this, argue that research programs should consider the three
      dimensions: (a) dynamics of movements; (b) multivariate measures and; (c) dynamic
      statistical parameters. Only with an extended perspective on theoretical and
      methodological accounts, one would be able to integrate the dynamics of actions
      into theoretical advances.

PMID- 30210381
TI  - Coping Humor of Entrepreneurs: Interaction Between Social Culture and
      Entrepreneurial Experience.
AB  - It is feasible to deal with the high pressures in entrepreneurship using humor.
      This paper studies the effect of interaction between entrepreneurs' perception of
      social culture and entrepreneurial experience (including experience with
      entrepreneurial failure and current company performance) on coping humor of
      entrepreneurs with a sample of 171 entrepreneurs from Bohai Rim in China.
      Regression analysis revealed that entrepreneurs would be more likely to adopt
      coping humor when they perceived supportive social culture to entrepreneurship
      and had experienced entrepreneurial failure or when they perceived supportive
      social culture to entrepreneurship and had good current business. This study
      contributes to the literature of the theory of humor, the culture of
      entrepreneurship, and entrepreneurial failure.

PMID- 30210380
TI  - Preference for Fractal-Scaling Properties Across Synthetic Noise Images and
      Artworks.
AB  - A large number of studies support the notion that synthetic images within a
      certain intermediate fractal-scaling range possess an intrinsic esthetic value.
      Interestingly, the fractal-scaling properties that define this intermediate range
      have also been found to characterize a vast collection of representational,
      abstract, and graphic art. While some have argued that these statistic properties
      only serve to maximize the visibility of the artworks' spatial structure, others
      argue that they are intrinsically tied to the artworks' esthetic appeal. In this
      study, we bring together these two threads of research and make a direct
      comparison between visual preference for varying fractal-scaling characteristics
      in both synthetic images and artworks. Across two studies, viewers ranked and
      rated sets of synthetic noise images and artworks that systematically varied in
      fractal dimension for liking, pleasantness, complexity, and interestingness. We
      analyzed both average and individual patterns of preference between the two image
      classes. Average preference peaked for intermediate fractal dimension values for
      both categories, but individual patterns of preferences for both high and low
      values also emerged. Correlational analyses indicated that individual preferences
      between the two image classes remained moderately consistent and were improved
      when the fractal dimensions between synthetic images and artworks were more
      closely matched. Overall, these findings further support the role of fractal
      scaling statistics both as a key determinant of an object's esthetic value and as
      a valuable predictor of individual differences in esthetic preference.

PMID- 30210382
TI  - Points and Stripes: A Novel Technique for Masking Biological Motion Point-Light
      Stimuli.
AB  - Human articulated motion can be readily recognized robustly even from
      impoverished so-called point-light displays. Such sequence information is
      processed by separate visual processing channels recruiting different stages at
      low and intermediate levels of the cortical visual processing hierarchy. The
      different contributions that motion and form information make to form
      articulated, or biological, motion perception are still under investigation. Here
      we investigate experimentally whether and how specific spatio-temporal features,
      such as extrema in the motion energy or maximum limb expansion, indicated by the
      lateral and longitudinal extension, constrain the formation of the
      representations of articulated body motion. In order to isolate the relevant
      stimulus properties we suggest a novel masking technique, which allows to
      selectively impair the ankle information of the body configuration while keeping
      the motion of the point-light locations intact. Our results provide evidence that
      maxima in feature channel representations, e.g., the lateral or longitudinal
      extension, define elemental features to specify key poses of biological motion
      patterns. These findings provide support for models which aim at automatically
      building visual representations for the cortical processing of articulated motion
      by identifying temporally localized events in a continuous input stream.

PMID- 30210383
TI  - Anxiety and Psycho-Physiological Stress Response to Competitive Sport Exercise.
AB  - Introduction: Sport is recognized as beneficial for health. In certain situation
      of practice, it nevertheless appears likely to induce a stress response. Anxiety
      is a stress response-modulating factor. Our objective is to characterize the role
      of anxiety in the stress response induced by a selective physical exercise.
      Method: Sixty-three young male military conducted a selective sporting running
      event (a 8-km commando-walk) and were recorded the day before, the day of the
      race, and the day after. The variables were psychometric [personality
      questionnaires, coping and anxious/stress state, and physiological (nocturnal
      heart rate variability and actigraphy)]. The subjects were classified, using
      scores on anxiety questionnaires at baseline, into two groups according to their
      anxious (G ANX) or non-anxious (G N-ANX). Results: Before the race, the G ANX was
      characterized by a lower level of self-esteem, higher scores in dysfunctional
      coping and a greater perceived stress compared to the G N-ANX. Compared to G N
      ANX, the stress response to the exercise was higher in G ANX: G ANX exhibited
      (Selye, 1950) in immediate post-exercise, greater level in activation markers,
      and mental fatigue associated with a same level of physical fatigue and (Kim et
      al., 2018) in nocturnal post-exercise, an increase in sympathetic activation
      associated with a higher sleep fragmentation. Conclusion: A competition selection
      sport exercise causes a stress response, particularly for anxious subjects.
      Anxious status could be involved in the risk of emergence of overtraining in
      sport practice. These results must be taken into account when sport practice is
      used for anxiety management.

PMID- 30210384
TI  - High Entrepreneurship, Leadership, and Professionalism (HELP): A New Resource for
      Workers in the 21st Century.
AB  - World of work in the 21st century is characterized by instability, insecurity,
      and continuous change. To face these challenges of the post-modern era, workers
      are required to use their personal resources. A new construct called high
      entrepreneurship, leadership, and professionalism (HELP) is a preventive resource
      that helps maintain, improve, and find work in uncertain or dynamic conditions.
      This study aims to examine the personality correlates of HELP in Italian workers
      and identify different clusters based on HELP and other variables, such as
      workplace relational civility and flourishing. To this end, the following
      instruments were administered to 204 Italian workers: the HELP questionnaire, the
      Big Five Questionnaire, the Workplace Relational Civility Scale, and the
      Flourishing Scale. The personality correlates of HELP underscored the role of
      conscientiousness (and its subdimension perseverance) and extraversion (and its
      subdimension dominance). The cluster analysis identified three clusters
      characterized by high, average, and low HELP scores. Participants in the first
      cluster with high HELP scores appeared to possess higher perseverance, dominance,
      workplace relational civility, especially readiness, and higher flourishing than
      those in the other two groups. The present results can open new opportunities for
      future research and interventions in a primary prevention perspective to foster
      resources for workers and healthy organizations in the 21st century.

PMID- 30210386
TI  - Does Separating Intentionality From Mental Representation Imply Radical
      Enactivism?
AB  - Traditionally, intentionality is regarded as that feature of all and only mental
      states - paradigmatically beliefs and desires - in virtue of which they are
      directed at or are about something. The problem of intentionality is to explain
      how it fits into the natural order given the intuition that no physical entity
      can be intentionally directed in this sense. The basic assumption of this paper,
      proposed by enactivists, is that failure to naturalize intentionality and mental
      representation is partly due to the fact that most participants in the debate
      take intentionality and mental representation to be equivalent. In contrast, it
      is proposed to treat intentionality as a feature of whole embodied agents
      (paradigmatically organisms) who can be directed at objects and states of affairs
      in various ways, while representation should be regarded as a feature of mental
      states (and their respective vehicles or underlying mechanisms). The present
      paper develops and motivates the distinction, applies it to Metzinger's project
      of naturalizing phenomenal representation, and demonstrates the range of
      theoretical options with respect to a delineation of cognition given the enactive
      proposal. It is taken as problematic that enactivism takes the realm of cognition
      to be identical to the realm of biology. Instead, a constraint on a theory of
      intentionality and representation is that it should delineate the subject matter
      of cognitive science and distinguish it from other sciences, also to leave room
      for the possibility of artificial intelligence. One important implication of the
      present proposal is that there can be creatures which can be intentionally
      directed without having the capacity to represent. That is, their intentionality
      is restricted to being able to be directed at existent things. Only creatures in
      possession of the right kind of neurocognitive architecture can produce and
      sustain representations in order to be directed at non-existent things. It is
      sketched how this approach conceives of intentionality as a developmental and
      layered concept, allowing for a hierarchical model of varieties of
      intentionality, ranging from the basic pursuit of local environmental goals to
      thoughts about fictional objects.

PMID- 30210385
TI  - A Review of the Academic and Psychological Impact of the Transition to Secondary
      Education.
AB  - The transition from primary to secondary education is one of the most stressful
      events in a young person's life (Zeedyk et al., 2003) and can have a negative
      impact on psychological well-being and academic achievement. One explanation for
      these negative impacts is that the transition coincides with early adolescence, a
      period during which certain psychological disorders (i.e., anxiety disorders)
      become more salient (Kessler et al., 2005) and marked social, biological, and
      psychological development occurs (Anderson et al., 2000). This review evaluates
      the existing literature on the psychological and academic impacts of the
      transition to secondary education on young adolescents. We examine the factors
      that plausibly increase or mitigate the risk of developing mental health issues
      and/or a decline in academic performance during the transition to secondary
      education. We also review the interplay between psychological health and academic
      achievement across and beyond the transition. We conclude with a summary of what
      schools and parents can learn from these findings to support children in a
      successful transition into secondary education.

PMID- 30210387
TI  - The Influence of Early Temperament on Language Development: The Moderating Role
      of Maternal Input.
AB  - Temperament is an individual aspect that strictly affects infants and children
      engagement with the environment and it is supposed to play a role in the
      acquiring of new competences. Several studies focused on the possible influence
      of temperament in the process of language acquisition in early childhood
      reporting not consistent findings. Since maternal input is a variable that has
      been widely associated with infant language development this longitudinal study
      aimed to explore the role of the quality of maternal input in the temperament
      language association. We hypothesized that the longitudinal association between
      early infant temperament and language production is moderated by the quality of
      maternal input during the first year of life. Infant temperament at 3 months and
      maternal linguistic input (lexical diversity and syntactic complexity) during
      spontaneous mother-infant interactions at 6, 9, and 12 months were assessed.
      Language competences were evaluated at the end of the second year: language
      production at 18 months with the CDI and child syntactic complexity at 24 months
      during spontaneous speech. Results showed significant moderating effects of
      syntactic complexity and lexical variability of maternal input at 6 and 9 months
      on the association of duration of orienting abilities and later language
      production. Infants with greater attentional abilities and with mothers who spoke
      to them with a more complex and variable input showed the better language
      outcomes. The association between infant distress to limitations and child
      language was not moderated by maternal input. No effects were found when
      considering the temperamental scale smile and laugher. Attentional control
      temperamental characteristics could help the infant to be more focus on maternal
      input throughout the first year of life and could consequently facilitate
      language development. Our findings underlined the necessity to explore infant
      development considering the interaction between individual and contextual
      factors.

PMID- 30210388
TI  - Effectiveness of Art Therapy With Adult Clients in 2018-What Progress Has Been
      Made?
AB  - In the year 2000, an important art therapy literature review addressed an
      essential question-does art therapy work? It discussed 17 articles dealing with
      the issue of the effectiveness of art therapy. Two decades later, this research
      field has extended its scope and is flourishing. Several current reviews of
      research work have described the broad range of methods implemented today, which
      includes qualitative and quantitative studies; other reviews have focused on art
      therapy with specific populations, or by age group. The aim of this systematic
      literature review is to contribute to the ongoing discussion in the field by
      exploring the latest studies dealing with the effectiveness of art therapy with a
      broad scope of adult clients. We conducted a comprehensive search in four
      databases and review of every quantitative article that has addressed outcome
      measures in the art therapy field from 2000 to 2017. This paper presents the
      latest 27 studies in the field that examine the effectiveness of art therapy with
      adult clients and divides them into seven clinical categories: cancer patients,
      clients coping with a variety of medical conditions, mental health clients,
      clients coping with trauma, prison inmates, the elderly, and clients who have not
      been diagnosed with specific issues but face ongoing daily challenges. It
      underscores the potential effects of art therapy on these seven clinical
      populations, and recommends the necessary expansions for future research in the
      field, to enable art therapy research to take further strides forward.

PMID- 30210389
TI  - All That Glitters Is Not Grit: Three Studies of Grit in University Students.
AB  - The present research looked at the importance of the concept of grit in
      University students based on a mixed-method approach. Study 1 comprised 440
      University students. All were given the Grit Scale, the Perceived Stress Scale,
      the short Warwick-Edinburgh Mental Well-being Scale, the Office of National
      Statistics Well-being items and the Self-Control Scale. Levels of grit were
      significantly higher in female students, older students and postgraduates. Grit
      correlated highest with self-control. Study 2 looked at 340 University students.
      In addition to measuring self-control, mental well-being and grit, measures of
      resilience and mindsets were also added. A construct validity test of the Grit
      Scale showed that high grit scorers had significantly higher levels of self
      control and mental well-being, were more resilient and were more likely to have a
      more growth oriented mindset. Grit varies with age and is most closely associated
      with the concept of self-control. The third study was a qualitative investigation
      with 10 successful graduates. Semi-structured interviews were coded using
      thematic analysis. Three broad themes emerged. The first, Passion and
      Perseverance, included themes of having short and long terms goals, resilience,
      dedication, and endurance. The second, Self-Control, included time management,
      self-awareness, prioritizing tasks and knowing strengths and weaknesses. The
      third theme identified was Positive Mindsets. This included having a positive
      attitude toward learning, the importance of feedback and constructive criticism
      and that success is not materialistic. The qualitative research has helped
      "unpack" concepts from the grit research and may enable University tutors to
      guide students better. Though these studies were only conducted in one English
      University, they have been stepping stones in our quest to discover what are the
      most important factors in determining student academic success? The development
      and piloting of our new Uni-Stride Scale, is the next step in this process.

PMID- 30210392
TI  - A Cross-Level Study on Family Involvement and Job Satisfaction.
AB  - This study aims to explore how various dynamics of working couples' family
      involvement shape their job satisfaction. With a sample collected from primary
      school teachers and spouses in China (n = 236), we use polynomial regression,
      response surface method, and multilevel structural equation model to capture the
      various dynamics of working couples' family involvement. We found that (1) high
      high spouses' family involvement has a negative impact on individual job
      satisfaction, and low-low spouses' family involvement is positively related to
      individual job satisfaction. (2) High-high spouses' family involvement benefits
      the creation of positive affect at the family level, which decreases family-to
      work conflict and mitigates its negative impacts on individual job satisfaction.
      (3) Working couple's perceived work-to-family enhancement moderates the
      relationship between spouses' family involvement and positive affect at the
      family level. This study extends our understanding of family-to-work spillover
      effects from the viewpoint of dynamic interaction between spouses at the cross
      level.

PMID- 30210390
TI  - Socioeconomic Risk and School Readiness: Longitudinal Mediation Through
      Children's Social Competence and Executive Function.
AB  - The association of socioeconomic status with academic readiness and school
      achievement is well established. However, the specific contributions of cognitive
      and social aspects of self-regulation, and potential reciprocal relations between
      them in the prediction of school readiness and early school achievement have not
      previously been examined. This study examined mediational processes involving
      children's executive function (EF) skills at 58 months and Grade 1 (G1) and
      social competence in Kindergarten (K) and G1, as potential pathways by which
      early-life poverty-related risks influence Grade 2 (G2) math and reading
      achievement. Data came from the Family Life Project, which is a prospective
      longitudinal study of 1,292 children and families followed from birth in
      primarily low-income, non-urban counties in Pennsylvania (PA) and North Carolina
      (NC). Autoregressive cross-lagged mediation analyses indicated that EF at 58
      months through EF at G1 mediated negative associations between cumulative risk
      exposure and academic skills, with this pathway mediating 36% of the total
      effect. Furthermore, social competence at K through EF at G1 mediated negative
      associations between early-life cumulative socioeconomic risk and academic
      skills, mediating 16% of the total effect. These findings provide evidence that
      poverty-related risks can influence school readiness and academic achievement via
      EF. Additionally, these results provide preliminary support for the premise that
      social competence through EF is a pathway by which cumulative poverty-related
      risk predicts early academic competence. Our findings are consistent with studies
      demonstrating developmental associations between EF and social competence.
      Furthermore, our findings are consistent with prekindergarten programs for
      children in poverty that emphasize both cognitive and social aspects of self
      regulation.

PMID- 30210394
TI  - Bayesian Revision vs. Information Distortion.
AB  - The rational status of the Bayesian calculus for revising likelihoods is
      compromised by the common but still unfamiliar phenomenon of information
      distortion. This bias is the distortion in the evaluation of a new datum toward
      favoring the currently preferred option in a decision or judgment. While the
      Bayesian calculus requires the independent combination of the prior probability
      and a new datum, information distortion invalidates such independence (because
      the prior influences the datum). Although widespread, information distortion has
      not generally been recognized. First, individuals are not aware when they
      themselves commit this bias. In addition, it is often hidden in more obvious
      suboptimal phenomena. Finally, the Bayesian calculus is usually explained only
      with undistortable data like colored balls drawn randomly. Partly because
      information distortion is unrecognized by the individuals exhibiting it, no way
      has been devised for eliminating it. Partial reduction is possible in some
      situations such as presenting all data simultaneously rather than sequentially
      with revision after each datum. The potential dangers of information distortion
      are illustrated for three professional revision tasks: forecasting, predicting
      consumer choices from internet data, and statistical inference from experimental
      results. The optimality of the Bayesian calculus competes with people's natural
      desire that their belief systems remain coherent in the face of new data.
      Information distortion provides this coherence by biasing those data toward
      greater agreement with the currently preferred position-but at the cost of
      Bayesian optimality.

PMID- 30210391
TI  - Dynamics of Simultaneous and Imitative Bodily Coordination in Trust and Distrust.
AB  - Body synchronization between interacting people involves coordinative movements
      in time, space and form. The introduction of newer technologies for automated
      video analysis and motion tracking has considerably improved the accurate
      measurement of coordination, particularly in temporal and spatial terms. However,
      the form of interpersonal coordination has been less explored. In the present
      study we address this gap by exploring the effect of trust on temporal and
      morphological patterns of interpersonal coordination. We adapted an optical
      motion-capture system to record spontaneous body movements in pairs of
      individuals engaged in natural conversations. We conducted two experiments in
      which we manipulated trust through a breach of expectancy (Study 1: 10 trustful
      and 10 distrustful participants) and friendship (Study 2: 20 dyads of friends and
      20 dyads of strangers). In Study 1, results show the participants' strong, early
      mirror-like coordination in response to the confederates' breach of trust. In
      Study 2, imitative coordination tended to be more pronounced in pairs of friends
      than in pairs of non-friends. Overall, our results show not only that listeners
      move in reaction to speakers, but also that speakers react to listeners with a
      chain of dynamic coordination patterns affected by the immediate disposition of,
      and long-term relationship with, their interlocutors.

PMID- 30210393
TI  - Patterns of Posttraumatic Stress Disorder Symptoms and Posttraumatic Growth in an
      Epidemiological Sample of Chinese Earthquake Survivors: A Latent Profile
      Analysis.
AB  - Background: Posttraumatic stress disorder (PTSD) and posttraumatic growth (PTG)
      are different psychological outcomes triggered by exposure to extraordinarily
      traumatic events. In this study, we aimed to examine patterns of co-occurrence
      between DSM-5 PTSD symptoms and PTG, among natural disaster survivors, and to
      clarify whether empirically-based subgroups differed by several specific
      predictors. Methods: Latent profile analysis was used to examine patterns of self
      reported PTSD symptoms and PTG in an epidemiological sample of 1063 Chinese
      earthquake survivors. Results: Three distinct profiles were identified, involving
      high PTSD/high PTG, mild PTSD/mild PTG, and mild PTSD/high PTG. Class membership
      was predicted by several variables, especially different sources of perceived
      social support. Conclusion: Our findings contribute to the knowledge about the
      coexisting patterns of PTSD and PTG, and provide suggestions for identifying high
      risk individuals and providing effective interventions in clinical practice.

PMID- 30210395
TI  - Goal Orientations and Activation of Approach Versus Avoidance Motivation While
      Awaiting an Achievement Situation in the Laboratory.
AB  - While some students try to give their best in an achievement situation, others
      show disengagement and just want to get the situation over and done with. The
      present study investigates the role of students' tendencies for approach or
      avoidance motivation while anticipating tasks and the corresponding activation of
      the approach/avoidance motivational system as indicated by transient changes of
      EEG alpha asymmetry. Overall, 62 students (50 female; age: M = 23.8, SD = 3.5)
      completed a goal orientation questionnaire (learning goals, performance-approach,
      performance-avoidance, and work avoidance). They joined a laboratory experiment
      where EEG was recorded during resting condition as well as when students were
      anticipating tasks. Standard multiple regression analysis showed that higher
      values on performance-avoidance were related to a higher activation of the
      approach system whereas higher values on work avoidance were related to a higher
      activation of the avoidance system. Results question present assumptions about
      avoidance related goal orientations.

PMID- 30210396
TI  - A Dual Mechanism of Cognition and Emotion in Processing Moral-Vertical Metaphors.
AB  - A moral concept involves two main factors: moral cognition (indicated by
      morality) and emotion (indicated by emotionality). The cognitive mechanism
      underlying moral metaphors on the vertical dimension (e.g., moral-up, immoral
      down) was investigated in three experiments using implicit association tests. The
      results of Experiment 1 show a stronger association of "moral-up, immoral-down"
      between words high in morality and vertical space than between words low in
      morality and vertical space, which indicates that cognitive factors of morality
      facilitate the processing of vertical spatial metaphors of moral concepts.
      Experiment 2, employing moral words different in emotionality, reveals a stronger
      association of "moral-up, immoral-down" between words high in emotionality and
      vertical space than between words low in emotionality and vertical space, which
      shows that emotional factors of morality facilitate the processing of vertical
      spatial metaphors of moral concepts. A comparison between the two experiments
      suggests a faster response to emotion than to moral cognition and similar
      association strengths of the two factors with verticality. Using words high in
      morality and emotionality, Experiment 3 shows that a combination of the two
      conditions (i.e., high morality and high emotionality) leads to a stronger tie
      with verticality than either condition. The above three experiments indicate that
      both moral cognition and emotion facilitate the processing of vertical spatial
      metaphor of moral concepts, and the forces of the two, which jointly affect the
      metaphorical connection between morality and verticality, are basically equal,
      although the processing of emotionality is faster than that of morality.

PMID- 30210397
TI  - Symptom Presentation in Idiopathic Environmental Intolerance With Attribution to
      Electromagnetic Fields: Evidence for a Nocebo Effect Based on Data Re-Analyzed
      From Two Previous Provocation Studies.
AB  - Individuals with idiopathic environmental illness with attribution to
      electromagnetic fields (IEI-EMF) claim they experience adverse symptoms when
      exposed to electromagnetic fields (EMFs) from mobile telecommunication devices.
      However, research has consistently reported no relationship between exposure to
      EMFs and symptoms in IEI-EMF individuals. The current study investigated whether
      presence of symptoms in IEI-EMF individuals were associated with a nocebo effect.
      Data from two previous double-blind provocation studies were re-analyzed based on
      participants' judgments as to whether or not they believed a telecommunication
      base station was "on" or "off". Experiment 1 examined data in which participants
      were exposed to EMFs from Global System for Mobile Communication, Universal
      Mobile Telecommunications System, and sham base station signals. In Experiment 2,
      participants were exposed to EMFs from Terrestrial Trunked Radio
      Telecommunications System and sham base station signals. Our measures of
      subjective well-being indicated IEI-EMF participants consistently reported
      significantly lower levels of well-being, when they believed the base station was
      "on" compared to "off". Interestingly, control participants also reported
      experiencing more symptoms and greater symptom severity when they too believed
      the base station was "on" compared to "off". Thus, a nocebo effect provides a
      reasonable explanation for the presence of symptoms in IEI-EMF and control
      participants.

PMID- 30210398
TI  - Combining Acceptance and Commitment Therapy With Adventure Therapy to Promote
      Psychological Wellbeing for Children At-Risk.
AB  - With high rates of psychological distress reported amongst children
      internationally, the development and evaluation of new program initiatives is
      critical in order to meet the challenge of this burgeoning issue. Both acceptance
      and commitment therapy and adventure therapy are emerging as popular strategies
      to elevate psychological wellbeing. This small-scale program evaluation focuses
      on nine upper primary school-aged children enrolled in a specialist school in
      Australia for children with challenging behavior and/or emotional needs.
      Participants completed a newly developed 8-week intervention entitled 'ACT in the
      Outdoors' which combined key principles of both acceptance and commitment therapy
      and adventure therapy. The program was evaluated via a combination of pre and
      post participant psychological measures, and post interviews with participants
      and teachers. The results of this small-scale preliminary evaluation suggest that
      a portion of the participating children reported improvements in psychological
      wellbeing and skill development. Improvements appear to be mitigated by
      attendance and level of psychological wellbeing upon program entry. Based on this
      premise, the results suggest that more research is warranted to further
      understand the potential benefit of this innovative interdisciplinary approach.

PMID- 30210400
TI  - The Big-Fish-Little-Pond Effect on Academic Self-Concept: A Meta-Analysis.
AB  - The Big-fish-little-Pond effect is well acknowledged as the negative effect of
      class/school average achievement on student academic self-concept, which
      profoundly impacts student academic performance and mental development. Although
      a few studies have been done with regard to this effect, inconsistence exists in
      the effect size with little success in finding moderators. Here, we present a
      meta-analysis to synthesize related literatures to reach a summary conclusion on
      the BFLPE. Furthermore, student age, comparison target, academic self-concept
      domain, student location, sample size, and publication year were examined as
      potential moderators. Thirty-three studies with fifty-six effect sizes (total N =
      1,276,838) were finally included. The random effects model led to a mean of the
      BFLPE at beta = -0.28 (p < 0.001). Moreover, moderator analyses revealed that the
      Big-Fish-Little-Pond effect is an age-based process and an intercultural
      phenomenon, which is stronger among high school students, in Asia and when verbal
      self-concept is considered. This meta-analysis is the first quantitative
      systematic overview of BFLPE, whose results are valuable to the understanding of
      BFLPE and reveal the necessity for educators from all countries to learn about
      operative means to help students avoid the potential negative effect. Future
      research expectations are offered subsequently.

PMID- 30210399
TI  - Not All Phrases Are Equally Attractive: Experimental Evidence for Selective
      Agreement Attraction Effects.
AB  - Research on memory retrieval during sentence comprehension suggests that
      similarity-based interference is mediated by the grammatical function of the
      distractor. For instance, Van Dyke and McElree (2011) observed interference
      during retrieval for subject-verb thematic binding when the distractor occurred
      as an oblique argument inside a prepositional phrase (PP), but not when it
      occurred as a core argument in direct object position. This contrast motivated
      the proposal that constituent encodings vary in the distinctiveness of their
      memory representations based on an argument hierarchy, which makes them
      differentially susceptible to interference. However, this hypothesis has not been
      explicitly tested. The present study uses an interference paradigm involving
      agreement attraction (e.g., Wagers et al., 2009) to test whether the argument
      status of the distractor determines susceptibility to interference. Results from
      two self-paced reading experiments show a clear contrast: agreement attraction is
      observed for oblique arguments (e.g., PP distractors), but attraction is
      nullified for core arguments (i.e., direct object and subject distractors). A
      follow-up experiment showed that this contrast cannot be reduced to the syntactic
      position of the distractor, favoring an account based on the semantic properties
      of the distractor. These findings support the proposal that interference is
      mediated by the argument status of the distractor and extend previous results by
      showing that the effect generalizes to a broader set of syntactic contexts and a
      wider range of syntactic dependencies. More generally, these results motivate a
      more nuanced account of real-time agreement processing that depends on both
      retrieval and encoding mechanisms.

PMID- 30210401
TI  - Commentary: The Impact of Digital Technology on Psychological Treatments and
      Their Dissemination.

PMID- 30210402
TI  - Perspective-Taking in Sentence Comprehension: Time and Empathy.
AB  - This study examines the neural substrate of perspective-taking by analyzing the
      electroencephalographic (EEG) activity elicited by the auditory comprehension of
      sentences for which the comprehender had to adopt the perspective of the person
      described in them. Recent studies suggest that the ability of perspective-taking
      can be an integrative function of temporal and spatial information processing. We
      thus examined the independence and possible interaction of human perspective
      shifts and temporal perspective-taking by utilizing Japanese subsidiary verbs for
      giving, namely -ageru and -kureru. We manipulated human perspective shifts and
      temporal perspective-taking independently in experimental sentences by
      syntactically changing the subject and the object between the speaker and a third
      person, while we manipulated the tense to be past or non-past tense via sentence
      final particles ru/ta (non-past/past). The EEG analyses via electrodes indicated
      the suppression of the beta band for human perspective shifts in sentences in non
      past tense and the absence of such suppression in sentences in past tense. The
      analyses for the clusters of independent components indicated beta suppression
      for past tense against non-past tense in sentences without a human perspective
      shift. This response pattern suggests a close relationship between human
      perspective shifting and temporal perspective-taking. The beta suppression for
      the human perspective shift in our experiment can be understood as a replication
      of the previous EEG findings observed for perspective-taking in the presentation
      of visual images. The preceding findings and our result suggest that the ability
      or the function of perspective-taking is not specific to the modality.
      Furthermore, the generator of the beta suppression for past tense against non
      past tense without human perspective shifting was localized in the precuneus,
      which is consistent with recent findings indicating that the precuneus is deeply
      involved in time perception.

PMID- 30210403
TI  - Perceived Effort in Football Athletes: The Role of Achievement Goal Theory and
      Self-Determination Theory.
AB  - This study examined the motivational determinants of athletes perceived effort in
      football considering the four-stage motivational sequence at the contextual level
      proposed by Hierarchical Model of Intrinsic and Extrinsic Motivation: task
      involving climate, basic psychological needs, self-determined motivation (SDM),
      and perceived effort. Additionally, SEM multi-group analysis across different age
      groups (U15, U17, U19, and U21 years) and serial mediation of basic psychological
      needs (BPNs) and SDM on the task-involving motivational climate and the perceived
      effort were also analyzed. Two independent samples of male football athletes (N =
      403, N = 403), aged 13-20 years were enrolled in this study. The results support
      the adequacy of the structural model in explaining the perceived effort of
      football atheltes in all samples under analysis, and was invariant across U17,
      U19, and U21. However, it was not invariant across U15 and U17, U19 and U21.
      Furthermore, results from the serial mediation showed significant indirect
      effects in all samples, supporting self-determination theoretical assumptions,
      reinforcing the importance of BPNs satisfaction and behavioral regulation in the
      relation in analysis. The results show that when coaches promote a task-involving
      climate, the BPNs satisfaction of athletes improves. This climate will facilitate
      the regulation of their behaviors toward more autonomous forms of motivation,
      with positive outcomes in the athletes perceived effort.

PMID- 30210405
TI  - The Effect of Font Size on Children's Memory and Metamemory.
AB  - Recently, there has been a growing interest in the effect of perceptual features
      of learning materials on adults' memory and metamemory. Previous studies
      consistently have found that adults use font size as a cue when monitoring their
      learning, judging that they will remember large font size words better than small
      font size words. Most studies have not demonstrated a significant effect of font
      size on adults' memory, but a recent meta-analysis of these studies revealed a
      subtle memory advantage for large font words. The current study extended this
      investigation to elementary school children. First and fifth-sixth graders
      studied words for a free recall test presented in either large or small font and
      made judgments of learning (JOLs) for each word. As did adults, children
      predicted they would remember large font size words better than small font size
      words and, in fact, actually remembered the large font size words better. No
      differences were observed between the two age groups in the effect of font size
      on memory or metamemory. These results suggest that the use of font size as a cue
      when monitoring one's own learning is robust across the life span and, further,
      that this cue has at least some validity.

PMID- 30210404
TI  - The Promise and Challenges of Intensive Longitudinal Designs for Imbalance Models
      of Adolescent Substance Use.
AB  - Imbalance models of adolescent brain development attribute the increasing
      engagement in substance use during adolescence to within-person changes in the
      functional balance between the neural systems underlying socio-emotional,
      incentive processing, and cognitive control. However, the experimental designs
      and analytic techniques used to date do not lend themselves to explicit tests of
      how within-person change and within-person variability in socio-emotional
      processing and cognitive control place individual adolescents at risk for
      substance use. For a more complete articulation and a more stringent test of
      these models, we highlight the promise and challenges of using intensive
      longitudinal designs and analysis techniques that encompass many (often >10)
      within-person measurement occasions. Use of intensive longitudinal designs will
      lend researchers the tools required to make within-person inferences in
      individual adolescents that will ultimately align imbalance models of adolescent
      substance use with the methodological frameworks used to test them.

PMID- 30210406
TI  - What's Shared in Movement Kinematics: Investigating Co-representation of Actions
      Through Movement.

PMID- 30210407
TI  - Interior Color and Psychological Functioning in a University Residence Hall.
AB  - The research exploited a unique architectural setting of a university residence
      hall composed by six separate buildings that matched for every architectural
      detail and differed only for the interior color (violet, blue, green, yellow,
      orange, and red). Four hundred and forty-three students living in the six
      buildings for an average of 13.33 months participated in a study that assessed
      color preference (hue and lightness), lightness preference, and the effects of
      color on studying and mood. The results showed a preference for blue interiors,
      followed by green, violet, orange, yellow, and red. A preference bias was found
      for the specific color in which the student lived. Gender differences emerged for
      the preference of blue and violet. Room-lightness was significantly affected by
      the interior color. Room ceiling was preferred white. Blue as interior color was
      considered to facilitate studying activity. The use of differentiated colors in
      the six buildings was evaluated to significantly facilitate orienting and
      wayfinding. A significant relation was found between a calm mood and preference
      for blue.

PMID- 30210408
TI  - Working Memory With Emotional Distraction in Monolingual and Bilingual Children.
AB  - Extensive work has demonstrated the benefits of bilingualism on executive
      functioning (EF) across the lifespan. Concurrently, other research has shown that
      EF is related to emotion regulation (ER), an ability that is integral to healthy
      socio-emotional development. However, no research to date has investigated
      whether bilingualism-related advantages in EF can also be found in emotional
      contexts. The current study examined the performance of 93 children who were 9
      years old, about half of whom were bilingual, on the Emotional Face N-Back Task,
      an ER task used to assess the interference effect of emotional processing on
      working memory. Bilingual children were more accurate than monolingual children
      in both 1-back and 2-back conditions but were significantly slower than
      monolingual children on the 2-back condition. There were significant effects of
      emotional valence on reaction time, but these did not differ across language
      groups. These results confirm previous research showing better EF performance by
      bilinguals, but no differences in ER were found between language groups. Findings
      are discussed in the context of our current understanding of the ER literature
      with potential implications for previously unexplored differences between
      monolingual and bilingual children.

PMID- 30210409
TI  - Distractor Efficiency in an Item Pool for a Statistics Classroom Exam: Assessing
      Its Relation With Item Cognitive Level Classified According to Bloom's Taxonomy.
AB  - Multiple-choice items are one of the most commonly used tools for evaluating
      students' knowledge and skills. A key aspect of this type of assessment is the
      presence of functioning distractors, i.e., incorrect alternatives intended to be
      plausible for students with lower achievement. To our knowledge, no work has
      investigated the relationship between distractor performance and the complexity
      of the cognitive task required to give the correct answer. The aim of this study
      was to investigate this relation, employing the first three levels of Bloom's
      taxonomy (Knowledge, Comprehension, and Application). Specifically, it was
      hypothesized that items classified into a higher level of Bloom's classification
      would show a greater number of functioning distractors. The study involved 174
      items administered to a sample of 848 undergraduate psychology students during
      their statistics exam. Each student received 30 items randomly selected from the
      174-item pool. The bivariate results mainly supported the authors' hypothesis:
      the highest percentage of functioning distractors was observed among the items
      classified into the Application category (eta2 = 0.024 and Phi = 0.25 for the
      dichotomized measure). When the analysis controlled for other item features, it
      lost statistical significance, partly because of the confounding effect of item
      difficulty.

PMID- 30210411
TI  - How a Good Sleep Predicts Life Satisfaction: The Role of Zero-Sum Beliefs About
      Happiness.
AB  - Sleep, although a vital aspect of human functioning, has received scant attention
      in happiness research. This research examines the effect of sleep quality on life
      satisfaction, and one possible mechanism that bridges the two. One cognitive
      factor that might tie the relationship between sleep and life satisfaction is a
      belief about the (in) finite nature of happiness (zero-sum belief about
      happiness; ZBH), a mindset that occurs more under conditions of scarcity. Given
      the interconnections among experiences prompted by various types of scarcity
      (e.g., financial and calorie), we predicted that deprived cognitive resource
      caused by poor sleep may activate the ZBH, thereby hurting one's life
      satisfaction. As expected, we found that sleep quality predicted the
      participants' life satisfaction, even controlling for baseline variables. More
      importantly, this relationship was partially mediated by ZBH. This study opens
      interesting questions on a relatively unexamined role of non-social predictors,
      such as sleep, in well-being.

PMID- 30210412
TI  - Perspectives on Social Suffering in Interviews and Drawings of Palestinian Adults
      Crossing the Qalandia Checkpoint: A Qualitative Phenomenological Study.
AB  - The current study examined the psychological experience of Palestinians who daily
      cross an Israel Defense Forces (IDF) checkpoint to reach their schools or places
      of employment. The study employed an interpretative phenomenological analysis of
      semi-structured interviews and drawings to capture a depth insight regarding the
      psychological meaning of crossing the Qalandia checkpoint on a daily basis among
      20 adult participants (10 males, 10 females). Three themes emerged. The first
      theme described deep feelings of distress and desperation and included the
      categories of humiliation and dehumanization, non-existence, rage, and pessimism
      and helplessness. The second theme concentrated on the participants' coping
      strategies of avoidance and dissociation, which usually characterize maladaptive
      trauma coping style, as well as exhibited aggressiveness toward their fellow
      community members, while the third theme described the social fragmentation of
      the Palestinians' solidarity. Furthermore, three pictorial phenomena emerged from
      the participants' drawings: squared restricted drawings, the use of multiple
      black tiny objects, and the use of split drawings. These phenomena supported and
      validated participants' verbal expressions. We suggest understanding these
      findings in light of the term "social suffering."

PMID- 30210413
TI  - Examining the Structure of Negative Affect Regulation and Its Association With
      Hedonic and Psychological Wellbeing.
AB  - The present study examines the structure of negative affect regulation strategies
      by confirmatory factor analysis. A total of 264 students (n = 187 women, 65 men)
      (M = 24 years; SD = 9.32) took part in this study. Results show a good fit
      indices for a three facets model: (1) modification of situation (problem-directed
      action, seeking emotional and instrumental social support, psychological
      abandonment and social isolation); (2) attentional deployment and cognitive
      change (distraction, acceptance, gratitude, rumination, reappraisal,
      spirituality, and social comparison); and (3) response modification (suppression,
      active and passive physiological, humor and warmth, venting, confrontation, and
      regulated emotional expression). The scale validity is confirmed through
      correlations between the expanded of Mood Affect Regulation Scale dimensions
      including dimensions of dispositional reappraisal and suppression, and hedonic
      and psychological well-being. Participants report an adaptive profile with high
      psychological well-being, even if they report low positive affect, suggesting a
      greater relevance of eudaimonic than hedonic well-being for affect regulation.

PMID- 30210414
TI  - Public Space Users' Soundscape Evaluations in Relation to Their Activities. An
      Amsterdam-Based Study.
AB  - Understanding the relationship between people and their soundscapes in an urban
      context of innumerable and diverse sensory stimulations is a difficult endeavor.
      What public space users hear and how they evaluate it in relation to their
      performed or intended activities can influence users' engagement with their
      spaces as well as their assessment of suitability of public space for their needs
      or expectations. While the interaction between the auditory experience and
      activity is a topic gaining momentum in soundscape research, capturing the
      complexity of this relationship in context remains a multifaceted challenge. In
      this paper, we address this challenge by researching the user-soundscape
      relationships in relation to users' activities. Building on previous soundscape
      studies, we explore the role and interaction of three potentially influencing
      factors in users' soundscape evaluations: level of social interaction of users'
      activities, familiarity and expectations, and we employ affordance theory to
      research the ways in which users bring their soundscapes into use. To this end,
      we employ a mixed methods design, combining quantitative, qualitative and spatial
      analyses to analyze how users of three public spaces in Amsterdam evaluate their
      soundscapes in relation to their activities. We documented the use of an urban
      park in Amsterdam through non-intrusive behavioral mapping to collect spatial
      data on observable categories of activities, and integrated our observations with
      on site questionnaires on ranked soundscape evaluations and free responses
      detailing users' evaluations, collected at the same time from park users. One of
      our key findings is that solitary and socially interactive respondents evaluate
      their soundscapes differently in relation to their activities, with the latter
      offering higher suitability and lower disruption ratings than the former; this
      points to qualitatively different auditory experiences, analyzed further based on
      users' open-ended justifications for their evaluations. We provide a
      methodological contribution (adding to existing soundscape evaluation
      methodologies), an empirical contribution (providing insight on how users explain
      their soundscape evaluations in relation to their activities) and a policy and
      design-related contribution, offering additional insight on a transferable
      methodology and process that practitioners can employ in their work on the built
      environment to address the multisensory experience of public spaces.

PMID- 30210410
TI  - Affective Eye Contact: An Integrative Review.
AB  - In recent years, many studies have shown that perceiving other individuals'
      direct gaze has robust effects on various attentional and cognitive processes.
      However, considerably less attention has been devoted to investigating the
      affective effects triggered by eye contact. This article reviews research
      concerning the effects of others' gaze direction on observers' affective
      responses. The review focuses on studies in which affective reactions have been
      investigated in well-controlled laboratory experiments, and in which contextual
      factors possibly influencing perceivers' affects have been controlled. Two
      important themes emerged from this review. First, explicit affective evaluations
      of seeing another's direct versus averted gaze have resulted in rather
      inconsistent findings; some studies report more positive subjective feelings to
      direct compared to averted gaze, whereas others report the opposite pattern.
      These contradictory findings may be related, for example, to differences between
      studies in terms of the capability of direct-gaze stimuli to elicit feelings of
      self-involvement. Second, studies relying on various implicit measures have
      reported more consistent results; they indicate that direct gaze increases
      affective arousal, and more importantly, that eye contact automatically evokes a
      positively valenced affective reaction. Based on the review, possible
      psychological mechanisms for the positive affective reactions elicited by eye
      contact are described.

PMID- 30210415
TI  - The Australian Sheep-Goat Scale: An Evaluation of Factor Structure and Convergent
      Validity.
AB  - The Australian Sheep-Goat Scale (ASGS) is a commonly used measure of belief in
      the paranormal. The scale contains items that index extrasensory perception
      (ESP), psychokinesis (PK), and life after death (LAD). Although, research employs
      the ASGS as both a general (unidimensional) and factorial (multidimensional)
      measure, few studies have examined the appropriateness of these solutions.
      Accordingly, the present paper tested the psychometric integrity of the ASGS via
      two studies. Study 1 assessed ASGS factorial structure using confirmatory factor
      analysis. To achieve this, merging of ASGS data from previously published studies
      and ongoing work created a heterogeneous sample of 1,601 responses. Analysis
      revealed that a two-factor bifactor model best explained ASGS organization. This
      comprised a general overarching factor incorporating two subfactors (ESP and PK).
      Factor loadings and omega reliability supported a unidimensional structure for
      the most part. Removal of LAD items improved model fit because the factor added
      unnecessary complexity and undermined scale psychometric integrity. Study 2,
      using a supplementary composite sample of 320 respondents, assessed the
      convergent validity of the emergent ASGS model against a recently published
      Revised Paranormal Belief Scale (RPBS) bifactor solution. Comparison revealed
      high convergent validity. The general ASGS factor, despite deriving from only psi
      related dimensions (ESP and PK) predicted RPBS scores. This finding indicated
      that ASGS brevity relative to the RPBS is advantageous when assessing general
      belief in the paranormal. The ASGS, notwithstanding limited construct content,
      functions as an effective measure of paranormal belief. Additionally, Study 2
      replicated the bifactor structure identified in Study 1 and invariance testing
      supported invariance of form, factor loadings and item intercepts for this
      solution across Studies 1 and 2.

PMID- 30210416
TI  - Psychopathic Personality Traits Scale (PPTS): Construct Validity of the
      Instrument in a Sample of U.S. Prisoners.
AB  - The Psychopathic Personality Traits Scale (PPTS; Boduszek et al., 2016) is a
      personality-based psychopathy assessment tool consisting of four subscales:
      affective responsiveness, cognitive responsiveness, interpersonal manipulation,
      and egocentricity. Although the measure offers a promising alternative to other,
      more behaviorally weighted scales, to date the factor structure of the PPTS and
      differential predictive validity of its dimensions has only been tested in one
      study. Consequently, the objective of the present research was to assess
      construct validity, factor structure, and composite reliability of the PPTS
      within a sample of U.S. male and female incarcerated offenders (N = 772). Another
      goal was to test the predictive efficiency of the PPTS dimensions for different
      types of offences (serial killing, homicide, sex crimes, weapon-related crimes,
      domestic violence, white-collar crimes, property crimes, drug-related crimes),
      recidivism (i.e., number of incarcerations), time spent in prison, and gender.
      Dimensionality and construct validity of the PPTS was investigated using
      traditional CFA techniques, confirmatory bifactor analysis, and multitrait
      multimethod modelling (MTMM). Seven alternative models of the PPTS were estimated
      in Mplus using WLSMV estimator. An MTMM model with four grouping factors
      (affective responsiveness, cognitive responsiveness, interpersonal manipulation,
      and egocentricity) while controlling for two method factors (knowledge/skills and
      attitudes/beliefs) offered the best representation of the data. Good composite
      reliability and differential predictive validity was reported. The PPTS can be
      reliably used among prisoners from the United States.

PMID- 30210417
TI  - Parafoveal Processing in Chinese Sentence Reading: Early Extraction of Radical
      Level Phonology.
AB  - The present study separated radical level phonology from character level
      phonology to explore the reliance on phonology during Chinese sentence reading
      with eye movement recording in a boundary paradigm. Participants viewed sentences
      with either regular, irregular, orthographically dissimilar homophone, or
      orthographically dissimilar non-homophone previews for the targets. Both regular
      and irregular characters contained the target character as the phonetic radical,
      with the regular character sharing the identical sound with its target phonetic
      radical. In Experiment 1, the irregular previews were different from the target
      phonetic radicals both in the first consonant and final compound vowels. In
      Experiment 2, the irregular characters would be replaced by the semi-regular
      previews, which shared the same final compound vowels but not the first consonant
      with the target characters. The radical level phonological preview benefit was
      obtained by the comparison between regular and irregular characters, while the
      character level phonological preview benefit was shown by the visually dissimilar
      homophones compared with the unrelated control condition. The preview benefit
      from parafoveal regular characters compared with irregular characters was
      observed in the first fixation duration, suggesting the early activation of
      phonological codes at radical levels. However, this preview benefit depends on
      phonological overlapping between the phonetic radicals and their host characters;
      it could be activated only when the pronunciation of the phonogram was totally
      consistent with that of its phonetic radical. Furthermore, the null preview
      effect of visually dissimilar homophones indicates no activation of phonological
      codes at the character level during Chinese sentence reading.

PMID- 30210418
TI  - Vulnerable and Grandiose Narcissism Are Differentially Associated With Ability
      and Trait Emotional Intelligence.
AB  - We examined the association between two types of narcissism, grandiose and
      vulnerable, and self-reported as well as ability emotional intelligence (EI).
      Grandiose narcissism is characterized by high self-esteem, interpersonal
      dominance and a tendency to overestimate one's capabilities, whereas vulnerable
      narcissism presents defensive, avoidant and hypersensitive attitude in
      interpersonal relations. In the current study (n = 249) we found that vulnerable
      narcissism was significantly and negatively associated with trait (self-reported)
      EI; however, it did not correlate with ability (performance) EI. Grandiose
      narcissism was significantly positively connected with trait EI. Moreover, when
      the two EI scores were analyzed together in a single model, they were associated
      with grandiose narcissism in opposite directions. Specifically, trait EI showed a
      positive relation with grandiose narcissism, while ability EI negatively
      predicted this type of narcissism. The latter results are consistent with
      previous findings showing that individuals with high level of grandiose
      narcissism tend to overestimate their abilities. Vulnerable narcissism is
      probably connected with more realistic self-perception of emotional abilities.

PMID- 30210419
TI  - Eyes-Closed Resting EEG Predicts the Learning of Alpha Down-Regulation in
      Neurofeedback Training.
AB  - Neurofeedback training, which enables the trainee to learn self-control of the
      EEG activity of interest based on online feedback, has demonstrated benefits on
      cognitive and behavioral performance. Nevertheless, as a core mechanism of
      neurofeedback, learning of EEG regulation (i.e., EEG learning) has not been well
      understood. Moreover, a substantial number of non-learners who fail to achieve
      successful EEG learning have often been reported. This study investigated the EEG
      learning in alpha down-regulation neurofeedback, aiming to better understand the
      alpha learning and to early predict learner/non-learner. Twenty-nine participants
      received neurofeedback training to down-regulate alpha in two days, while eight
      of them were identified as non-learners who failed to reduce their alpha within
      sessions. Through a stepwise linear discriminant analysis, a prediction model was
      built based on participant's eyes-closed resting EEG activities in broad
      frequency bands including lower alpha, theta, sigma and beta 1 measured before
      training, which was validated in predicting learners/non-learners. The findings
      would assist in the early identification of the individuals who would not likely
      reduce their alpha during neurofeedback.

PMID- 30210420
TI  - The Multifaceted Nature of Alexithymia - A Neuroscientific Perspective.
AB  - Neuroscientific studies have mostly employed the 20-item Toronto Alexithymia
      Scale (TAS-20; Bagby et al., 1994a) for the assessment of alexithymia, a self
      report scale that assesses the alexithymia facets difficulty identifying
      feelings, difficulty describing feelings, and externally oriented thinking. These
      facets can be considered to capture difficulties in the cognitive processing of
      emotions associated with alexithymia. However, Nemiah and Sifneos' original
      conceptualization of alexithymia included also an affective component, a lack of
      imaginative capacities, which cannot be assessed using the TAS-20. Aiming to
      capture the entire alexithymia construct, the Bermond-Vorst Alexithymia
      Questionnaire (BVAQ; Vorst and Bermond, 2001) was developed, a self-report scale
      which assesses two affective facets (difficulty fantasizing and difficulty
      emotionalizing) in addition to three cognitive facets. Based on these facets, an
      affective and a cognitive dimension of alexithymia can be distinguished. By now,
      several neuroscientific studies have investigated the neural signatures of the
      different facets and dimensions of alexithymia. Here, I provide an overview of
      the history of the alexithymia facets and dimensions and review findings provided
      by functional and structural magnetic resonance imaging (MRI) studies that
      differentiated between the alexithymia facets and/or its affective and cognitive
      dimensions. I then provide a synopsis of the current neuroscientific evidence for
      dissociable substrates of alexithymia facets and dimensions. Finally, the
      scientific value and clinical implications of these findings are discussed.

PMID- 30210421
TI  - Risk-Taking and Impulsivity: The Role of Mood States and Interoception.
AB  - Objectives: The consequences of impulsive decisions and actions represent a major
      source of concern to the health and well-being of individuals and society. It is,
      therefore, crucial to understand the factors which contribute to impulsive
      behaviors. Here, we examined how personality traits of behavioral tendencies,
      interoceptive sensibility as well as transient mood states predict behavioral
      performance on impulsivity and risk-taking tasks. Method: 574 (121 males; age 18
      45) individuals completed self-report personality measures of impulsivity, reward
      sensitivity, punishment avoidance as well as interoceptive sensibility, undertook
      a mood assessment and performed a set of cognitive tasks: delay discounting
      (temporal impulsivity), probability discounting (risk-taking), and reflection
      impulsivity task. Data were interrogated using principal component analysis,
      correlations and regression analyses to test mutual relationships between
      personality traits, interoceptive sensibility, mood state and impulsive
      behaviors. Results: We observed a clear separation of measures used, both trait
      and behavioral. Namely, sensation-seeking, reward sensitivity and probability
      discounting reflected risk-taking. These were separate from measures associated
      with impulsivity, both trait (negative and positive urgency, premeditation,
      perseverance) and behavioral (delayed discounting and reflection impulsivity).
      This separation was further highlighted by their relationship with the current
      emotional state: positive affect was associated with increased risk-taking
      tendencies and risky decision-making, while negative emotions were related to
      heightened impulsivity measures. Interoceptive sensibility was only associated
      with negative emotions component. Conclusion: Our findings support the proposal
      that risk-taking and impulsivity represent distinct constructs that are
      differentially affected by current mood states. This novel insight enhances our
      understanding of impulsive behaviors.

PMID- 30210422
TI  - Romiplostim for the Emergency Management of Severe Immune Thrombocytopenia with
      Intracerebral Hemorrhage.
AB  - Currently, we lack well-established guidelines for the emergency management of
      severe immune thrombocytopenia (ITP) with life-threatening bleeding. We now
      report the management of two patients with severe ITP, complicated by substantial
      cerebral hemorrhage, requiring urgent surgery due to refractory intracranial
      hypertension. To rapidly boost platelet counts (PCs), corticosteroids,
      intravenous immunoglobulin, and iterative platelet transfusions were given; all
      were ineffectual. Romiplostim, a thrombopoietin receptor agonist, was then
      administered as an "on demand therapy," with the result that a rapid and
      sustained increase of PCs was achieved, thus allowing for postoperative
      hemostasis. Both patients recovered good neurological condition, suggesting the
      potential utility of romiplostim, in combined therapy, for the emergency
      management of severe ITP.

PMID- 30210424
TI  - Post-stroke BDNF Concentration Changes Following Physical Exercise: A Systematic
      Review.
AB  - Background: Research over the last two decades has highlighted the critical role
      of Brain-derived neurotrophic factor (BDNF) in brain neuroplasticity. Studies
      suggest that physical exercise may have a positive impact on the release of BDNF
      and therefore, brain plasticity. These results in animal and human studies have
      potential implications for the recovery from damage to the brain and for
      interventions that aim to facilitate neuroplasticity and, therefore, the
      rehabilitation process. Purpose: The aim of this study was to carry out a
      systematic review of the literature investigating how aerobic exercises and
      functional task training influence BDNF concentrations post-stroke in humans and
      animal models. Data Sources: Searches were conducted in PubMed (via National
      Library of Medicine), SCOPUS (Elsevier), CINAHL with Full Text (EBSCO), MEDLINE
      1946-present with daily updates (Ovid) and Cochrane. Study Selection: All of the
      database searches were limited to the period from January, 2004 to May, 2017.
      Data Extraction: Two reviewers extracted study details and data. The
      methodological quality of the studies that used animal models was assessed using
      the ARRIVE Guidelines, and the study that evaluated human BDNF was assessed using
      the PEDro Scale. Data Synthesis: Twenty-one articles were included in this
      review. BDNF measurements were performed systemically (serum/plasma) or locally
      (central nervous system). Only one study evaluated human BDNF concentrations
      following physical exercise, while 20 studies were experimental studies using a
      stroke model in animals. A wide variation was observed in the training protocol
      between studies, although treadmill walking was the most common type of
      intervention among the studies. Studies were of variable quality: the studies
      that used animal models scored from 8/20 to 15/20 according to the ARRIVE
      Guidelines. The only study that evaluated human subjects scored 5/10 according to
      the PEDro scale and, which indicates a quality classified as "fair". Conclusions:
      The results of the current systematic review suggest that aerobic exercise
      promotes changes in central BDNF concentrations post-stroke. On the other hand,
      BDNF responses following functional exercises, such as reaching training and
      Constraint Induced Movement Therapy (CIMT), seem to be still controversial. Given
      the lack of studies evaluating post-stroke BDNF concentration following physical
      exercise in humans, these conclusions are based on animal work.

PMID- 30210423
TI  - Lipid Paradox in Statin-Naive Acute Ischemic Stroke But Not Hemorrhagic Stroke.
AB  - Background: Low lipid level is associated with better cardiovascular outcome.
      However, lipid paradox indicating low lipid level having worse outcomes could be
      seen under acute injury in some diseases. The present study was designed to
      clarify the prognostic significance of acute-phase lipid levels within 1 day
      after admission for stroke on mortality in first-ever statin-naive acute ischemic
      stroke (IS) and hemorrhagic stroke (HS). Methods: This observational study was
      conducted using the data collected from Stroke Registry In Chang-Gung Healthcare
      System (SRICHS) between 2009 and 2012. Patients with recurrent stroke, onset of
      symptoms >1 day, and history of the use of lipid-lowering agents prior to index
      stroke were excluded. Stroke was classified into IS and hypertension-related HS.
      The primary outcomes were 30-day and 1-year mortality identified by linkage to
      national death registry for date and cause of death. Receiver operating
      characteristic (ROC) curve analysis and multivariate Cox proportional hazard
      models were used to examine the association of lipid profiles on admission with
      mortality. Results: Among the 18,268 admitted stroke patients, 3,746 IS and 465
      HS patients were eligible for analysis. In IS, total cholesterol (TC) <163.5
      mg/dL, triglyceride (TG) <94.5 mg/dL, low-density lipoprotein (LDL) <100 mg/dL,
      non-high-density lipoprotein cholesterol (non-HDL-C) <130.5 mg/dL, and TC/HDL
      ratio <4.06 had significantly higher risk for 30-day/1-year mortality with hazard
      ratio (HR) of 2.05/1.37, 1.65/1.31, 1.68/1.38, 1.80/1.41, and 1.58/1.38,
      respectively, compared with high TC, TG, LDL, non-HDL-C, and TC/HDL ratio (p <
      0.01 in all cases). In HS, lipid profiles were not associated with mortality,
      except HDL for 30-day mortality (p = 0.025) and high uric acid (UA)
      concentrations for 30-day and 1-year mortality (p = 0.002 and 0.012,
      respectively). High fasting glucose and high National Institute of Health Stroke
      Scale (NIHSS) score at admission were associated with higher 30-day and 1-year
      mortality in both IS and HS and low blood pressure only in IS (p < 0.05).
      Synergic effects on mortality were found when low lipids were incorporated with
      high fasting glucose, low blood pressure, and high NIHSS score in IS (p < 0.05).
      Conclusions: Lipid paradox showing low acute-phase lipid levels with high
      mortality could be seen in statin-naive acute IS but not in HS. The mortality in
      IS was increased when low lipids were incorporated with high fasting glucose, low
      blood pressure, and high NIHSS score.

PMID- 30210426
TI  - A Pilot Study Examining Speed of Processing Training (SPT) to Improve Processing
      Speed in Persons With Multiple Sclerosis.
AB  - Background: Individuals with Multiple Sclerosis (MS) have significant impairments
      in processing speed (PS) and such impairments may underlie other cognitive
      deficits common in MS and limit performance of everyday life activities.
      Objective: To examine the efficacy of a computerized PS intervention, Speed of
      Processing Training (SPT), in persons with MS on PS, memory and everyday
      activities. Methods: Twenty-one individuals with clinically definite MS and an
      objectively assessed impairment in PS were included in a controlled randomized
      clinical trial, randomly assigned to a treatment group or a control group.
      Participants were assessed prior to and within 1 week of completing the
      treatment. Outcome measures included traditional neuropsychological tests
      measuring PS and memory, and an assessment of PS in daily life activities.
      Results: The treatment group showed a significant improvement on
      neuropsychological tests of PS and new learning and memory. A significant
      improvement was additionally noted in the treatment group on measures of PS in
      everyday life. These changes were not observed in the control group. Conclusions:
      Results provide preliminary data in support of SPT in treating PS deficits in
      persons with MS. Additional research is needed with larger samples and more
      comprehensive outcome measures.

PMID- 30210425
TI  - Oscillatory Activity in the Cortex, Motor Thalamus and Nucleus Reticularis
      Thalami in Acute TTX and Chronic 6-OHDA Dopamine-Depleted Animals.
AB  - The motor thalamus (MTh) and the nucleus reticularis thalami (NRT) have been
      largely neglected in Parkinson's disease (PD) research, despite their key role as
      interface between basal ganglia (BG) and cortex (Cx). In the present study, we
      investigated the oscillatory activity within the Cx, MTh, and NRT, in normal and
      different dopamine (DA)-deficient states. We performed our experiments in both
      acute and chronic DA-denervated rats by injecting into the medial forebrain
      bundle (MFB) tetrodotoxin (TTX) or 6-hydroxydopamine (6-OHDA), respectively.
      Interestingly, almost all the electroencephalogram (EEG) frequency bands changed
      in acute and/or chronic DA depletion, suggesting alteration of all oscillatory
      activities and not of a specific band. Overall, delta (2-4 Hz) and theta (4-8 Hz)
      band decreased in NRT and Cx in acute and chronic state, whilst, alpha (8-13 Hz)
      band decreased in acute and chronic states in the MTh and NRT but not in the Cx.
      The beta (13-40 Hz) and gamma (60-90 Hz) bands were enhanced in the Cx. In the
      NRT the beta bands decreased, except for high-beta (Hbeta, 25-30 Hz) that
      increased in acute state. In the MTh, Lbeta and Hbeta decreased in acute DA
      depletion state and gamma decreased in both TTX and 6-OHDA-treated animals. These
      results confirm that abnormal cortical beta band are present in the established
      DA deficiency and it might be considered a hallmark of PD. The abnormal
      oscillatory activity in frequency interval of other bands, in particular the
      dampening of low frequencies in thalamic stations, in both states of DA depletion
      might also underlie PD motor and non-motor symptoms. Our data highlighted the
      effects of acute depletion of DA and the strict interplay in the oscillatory
      activity between the MTh and NRT in both acute and chronic stage of DA depletion.
      Moreover, our findings emphasize early alterations in the NRT, a crucial station
      for thalamic information processing.

PMID- 30210427
TI  - Morphofunctional Organization of the Connections From the Medial and Intermediate
      Parts of the Central Nucleus of the Amygdala Into Distinct Divisions of the
      Lateral Hypothalamic Area in the Rat.
AB  - Projections from the central nucleus of the amygdala (CEA) into the lateral
      hypothalamic area (LHA) show a very complex pattern. After injection of an
      anterograde tracer (Phaseolus vulgaris leucoagglutinin-PHAL) into the medial and
      intermediate parts of the CEA, we observed that labeled axons converged onto the
      caudal lateral LHA but provided distinct patterns in rostral tuberal regions.
      These projections were compared to that of neurons containing the peptides
      "melanin-concentrating hormone" (MCH) or hypocretin (Hcrt). Because the
      distribution of these neurons is stereotyped, it was possible to characterize
      distinct divisions into the LHA. Some of them in the rostral tuberal LHA [the
      dorsal (LHAd) and suprafornical regions (LHAs)] received a distinct innervation
      by projections that originated from neurons in respectively anterior or posterior
      regions of the medial part (CEAm) or from the intermediate part (CEAi) of the
      central nucleus. Therefore, this work illustrates that projections from the CEAm
      and CEAi converge into the caudal lateral LHA but diverge into the rostral
      tuberal LHA.

PMID- 30210428
TI  - Spinal Cord Changes After Laminoplasty in Cervical Compressive Myelopathy: A
      Diffusion Tensor Imaging Study.
AB  - Purpose: Validation of the efficacy of decompression surgery in patients with
      cervical myelopathy (CM) is important in terms of the recovery of the integrity
      of the spinal cord. However, to date, no longitudinal study has addressed the
      underlying pathological changes using diffusion tensor imaging (DTI) in CM
      patients. This study aimed to determine the diffusion metrics at the lesion as
      well as below the lesion level longitudinally in CM patients following
      laminoplasty using DTI. Methods: Twenty CM patients were analyzed and compared
      with 20 age-matched healthy controls. The primary outcome measure was the changes
      in the diffusion metrics [fractional isotropy (FA), mean diffusivity (MD), axial
      diffusivity (AD), and radial diffusivity (RD)]. The secondary outcome measure was
      the changes in the modified Japanese Orthopedic Association (mJOA) score.
      Diffusion metrics obtained from six region-of-interests (ROIs; 2 anterior, 2
      posterior, 2 lateral) at the lesion and below the lesion level (C7/T1) in
      preoperative and 6 months postoperative conditions were compared longitudinally.
      Results: The CM patients showed significant changes in their postoperative
      diffusion metrics for the anterior ROIs compared with the preoperative measures
      both at and below the lesion level. In the lateral and posterior cord, the
      preoperative AD value decreased after laminoplasty to the control at the lesion
      level. In contrast, MD and RD values at the lesion level and FA value at below
      the lesion level remained unchanged postoperatively. In addition, the
      postoperative anterior FA value was positively correlated with the postoperative
      mJOA score below the lesion level. Conclusion: This would be the first study
      showing changes in the spinal cord at the lesion as well as below the lesion
      level after laminoplasty in CM patients, which may be associated with functional
      recovery.

PMID- 30210429
TI  - Deep Brain Stimulation and Sleep-Wake Disturbances in Parkinson Disease: A
      Review.
AB  - Sleep-wake disturbances are common non-motor manifestations in Parkinson Disease
      (PD). Complex pathophysiological changes secondary to neurodegeneration in
      combination with motor symptoms and dopaminergic medications contribute to
      development of sleep-wake disturbances. The management of sleep complaints in PD
      is important as this symptom can affect daily activities and impair quality of
      life. Deep brain stimulation (DBS) is an effective adjunctive therapy for
      management of motor symptoms in PD. However, its effect on non-motor symptoms
      including sleep-wake disturbances is not widely understood. In this article, we
      reviewed studies assessing the effect of DBS at various therapeutic targets on
      sleep-wake disturbances. Of the studies examining the role of DBS in sleep-wake
      disturbances, the effect of subthalamic nucleus stimulation is most widely
      studied and has shown improvement in sleep quality, sleep efficiency, and sleep
      duration. Although, studies investigating changes in sleep with stimulation of
      thalamus, globus pallidus interna, and pedunculopontine nucleus are limited, they
      support the potential for modulation of sleep-wake centers with DBS at these
      sites. The mechanism by which DBS at different anatomical targets affects sleep
      wake disturbances in PD is unclear and may involves multiple factors, including
      improved motor symptoms, medication adjustment, and direct modulation of sleep
      wake centers.

PMID- 30210430
TI  - Primary Leptomeningeal Oligodendroglioma, IDH-Mutant, 1p/19q-Codeleted.
AB  - We present a case of a 43-year-old woman with a history of headaches and blurry
      vision. Ophthalmologic examination identified papilledema. MR imaging
      demonstrated a right parietal region mass with patchy areas of contrast
      enhancement and focal calcifications. Intraoperative examination and exploration
      revealed an extra-axial mass with no apparent parenchymal involvement.
      Microscopic examination revealed solid sheets of tumor cells with clear cell
      cytologic features and no discernable intra-parenchymal tumor component.
      Molecular studies demonstrated the presence of IDH1 IDH1 c.395G>A p.R132H and CIC
      c.601C>T p.R281W mutations and 1p/19q codeletion. The radiographic features,
      gross appearance, and microscopic and molecular characteristics of the mass
      support the diagnosis of primary leptomeningeal oligodendroglioma, IDH-mutant,
      1p/19-codeleted. This case represents one of a very few reported instances of
      molecularly-defined solitary, primary, intracranial oligodendroglioma, without
      definitive involvement of the brain parenchyma.

PMID- 30210431
TI  - Impact of Anesthetic Management on Safety and Outcomes Following Mechanical
      Thrombectomy for Ischemic Stroke in SWIFT PRIME Cohort.
AB  - Background and purpose: The optimal anesthetic management of acute ischemic
      stroke patients during mechanical thrombectomy (MT) remains controversial. In
      this post-hoc analysis, we investigated the impact of anesthesia type on clinical
      outcomes in patients included in SWIFT PRIME trial. Methods: Ninety-seven
      patients treated with MT were included. Patients treated in centers with general
      anesthesia (GA) policy (n = 32) were compared with those treated in centers with
      conscious sedation (CS) policy (n = 65). Primary outcomes studied included times
      to treatment initiation (TTI), rates of successful recanalization (TICI 2b/3),
      and functional independence (mRS 0-2 at 90 days). Secondary outcomes were adverse
      events, lowest systolic and diastolic blood pressures (LSBP and LDBP) during MT.
      Univariate analysis and multivariate regression logistic modeling were conducted.
      Results: The GA-policy and CS-policy groups presented comparable TTI (94 +/- 36
      min vs. 102 +/- 48 min; p = 0.44), rates of TICI 2b/3 recanalization (22/32
      [68.8%] vs. 51/65 [78.5%]; p = 0.32). CS-policy was associated to higher rate of
      functional independence than GA-policy, but the difference was not significant
      (43/65 [66.2%] vs. 16/32 [50.0%]; p = 0.18). GA-policy patients had a higher rate
      of postoperative pneumonia (11/32 [34.4%] vs. 8/65 [12.3%]; p = 0.02) and lower
      LSBP (110 [30,160] mmHg vs. 119 [77,170] mmHg; p = 0.03) and LDBP (55 (15,75)
      mmHg vs. 67 [40,121]; p < 0.001). When corrected for differences in baseline
      characteristics, GA-policy was associated with lower rate of functional
      independence (OR 0.32; p = 0.05). A 10-point increase in perprocedural LDBP was
      associated with an increased likelihood of favorable outcome (OR 1.51; p = 0.01).
      Conclusions: GA-policy for MT presented comparable TTI and rates of successful
      revascularization to CS-policy. However, GA-policy was associated with lower
      rates of functional independence and with higher incidence of perprocedural
      hypotension and postoperative pneumonia. Clinical Trial Registration: URL
      http://www.clinicaltrials.gov. Unique identifier: NCT01657461.

PMID- 30210433
TI  - Delayed Post-hypoxic Leukoencephalopathy (DPHL)-An Uncommon Variant of Hypoxic
      Brain Damage in Adults.
AB  - Delayed post-hypoxic leukoencephalopathy (DPHL) is an uncommon, potentially under
      recognized, cause of hypoxia induced white matter injury. It characteristically
      follows a biphasic course: After an initial phase of altered neurologic status a
      recovery occurs which is then followed by a recurring phase of neurologic
      deterioration, typically 2-4 weeks after the initial event. At this time white
      matter changes can be identified on MRI, which are the hallmark of DPHL. The
      characteristics and the typical MR-imaging signs of DPHL are discussed in this
      case report.

PMID- 30210432
TI  - Feasibility of Cognitive Functions Screened With the Montreal Cognitive
      Assessment in Determining ADL Dependence Early After Stroke.
AB  - Objective: To investigate the feasibility of assessing cognitive function using
      the Montreal Cognitive Assessment (MoCA) given 36-48 h post stroke to explain
      dependence in activities of daily living (ADL). Methods: This is a cross
      sectional, exploratory study. Cognitive function and basic ADL were assessed with
      the MoCA and the Barthel Index (BI), respectively, within 36-48 h of admission.
      Neurological functions were assessed with the National Institute of Health Stroke
      Scale (NIHSS) upon admittance to the hospital. Binary logistic regression
      analyses were performed to assess the feasibility of the MoCA in explaining ADL
      dependence. Results: Data were available for 550 patients (42% females, mean age
      69 years). Moderate correlations (rs > +0.30, p < 0.001) were found between the
      total score on the BI, MoCA, and visuospatial/executive functions. The regression
      analysis model including only MoCA as an independent variable had a high
      sensitivity for explaining ADL dependence. However, the model with independent
      variables of MoCA, NIHSS, and age had the best area under the curve value (0.74).
      Conclusions: Cognitive functions assessed with the MoCA partly explain ADL
      dependence 36-48 h post stroke. Stroke-related neurological deficits and age
      should be additional considerations.

PMID- 30210435
TI  - Sarcopenia and Muscle Functions at Various Stages of Alzheimer Disease.
AB  - Although sarcopenia is closely linked to dementia, particularly Alzheimer disease
      (AD), there are few studies examining the prevalence and associated factors of
      sarcopenia in subjects with AD. This study aimed to investigate the prevalence of
      sarcopenia, factors associated with sarcopenia in elderly subjects with AD, and
      differences in muscle functions of the upper and lower extremities and gait speed
      at various stages of AD. We evaluated handgrip and knee extension strength,
      muscle mass, and gait speed in 285 elderly outpatients with probable AD (mean age
      82. 0 +/- 5.3 years), including early AD (n = 82), mild AD (n = 90), and moderate
      AD (n = 113), and 67 elderly outpatients with normal cognition (NC) (mean age
      81.1 +/- 4.7 years). Sarcopenia was defined according to the consensus of the
      Asian Working Group for Sarcopenia. The prevalence rate of sarcopenia was
      significantly higher in early AD, mild AD, and moderate AD than in NC (11% in NC,
      36% in early AD, 45% in mild AD, and 60% in moderate AD of the female group, and
      13% in NC, 41% in early AD, 47% in mild AD, and 47% in moderate AD of the male
      group). Age, body mass index, and Mini-mental state examination score were
      associated with sarcopenia in female or male AD groups. Decreased muscle strength
      without loss of muscle mass of the upper and lower extremities in the female AD
      group and those of the lower extremity in the AD male group were found in early
      and mild stages. Both muscle strength and mass decreased in the moderate AD. Low
      gait speed was also found in the early female and male AD which progressed with
      advancing dementia. Subjects with AD, even the early stages of AD, showed a high
      prevalence rate of sarcopenia. Higher age, lower BMI, and lower MMSE score were
      associated with sarcopenia in the female or male AD. There were differences in
      muscle functions and physical performance between the stages of the female and
      male AD.

PMID- 30210437
TI  - High On-Treatment Platelet Reactivity in Danish Hyper-Acute Ischaemic Stroke
      Patients.
AB  - Objective: Early anti-platelet therapy is a cornerstone in the prevention of
      recurrent ischaemic stroke (IS) and transient ischaemic attacks (TIAs), although
      the responsiveness to anti-platelet medications varies among patients. Several
      studies have reported that patients with ischaemic stroke who exhibit high on
      treatment platelet reactivity (HTPR) 5-10 days after antiplatelet medication
      onset, have an increased risk of vascular events. In this study we aim to
      determine the prevalence of HTPR in the hyper-acute stroke phase less than 48 h
      from symptom onset, after the administration of a 300 mg bolus of oral
      clopidogrel in a real-world setting in Danish IS and TIA patients. Material and
      Methods: In total, 219 Danish patients with acute IS or TIA received 300 mg of
      oral clopidogrel on admission. Blood samples from all patients were analyzed
      using the VerifyNow P2Y12 system at 8-24 h after clopidogrel intake. Concomitant
      therapy and the intervals between ictus and blood collection, clopidogrel intake
      and blood collection, and blood sampling and analysis were recorded for all
      patients. Results: HTPR in the hyper-acute stroke phase was observed in 28.8%
      (63/219) samples. After adjustment for age, sex, co-morbidities, and co
      medications, none of the tested variables exhibited an association with HTPR or
      the platelet reaction unit value measured using the VerifyNow P2Y12 system.
      Conclusions: The recognition of HTPR to specific anti-platelet agents in the
      hyper-acute phase after stroke may be the first step toward interventions that
      may further minimize the early recurrent stroke risk. Further large randomized
      trials including clinical outcome assessments are necessary.

PMID- 30210434
TI  - Distortion of Visuo-Motor Temporal Integration in Apraxia: Evidence From Delayed
      Visual Feedback Detection Tasks and Voxel-Based Lesion-Symptom Mapping.
AB  - Limb apraxia is a higher brain dysfunction that typically occurs after left
      hemispheric stroke and its cause cannot be explained by sensory disturbance or
      motor paralysis. The comparison of motor signals and visual feedback to generate
      errors, i.e., visuo-motor integration, is important in motor control and motor
      learning, which may be impaired in apraxia. However, in apraxia after stroke, it
      is unknown whether there is a specific deficit in visuo-motor temporal
      integration compared to visuo-tactile and visuo-proprioceptive temporal
      integration. We examined the precision of visuo-motor temporal integration and
      sensory-sensory (visuo-tactile and visuo-proprioception) temporal integration in
      apraxia after stroke by using a delayed visual feedback detection task with three
      different conditions (tactile, passive movement, and active movement). The delay
      detection threshold and the probability curve for delay detection obtained in
      this task were quantitative indicators of the respective temporal integration
      functions. In addition, we performed subtraction and voxel-based lesion-symptom
      mapping to identify the brain lesions responsible for apraxia and deficits in
      visuo-motor temporal integration. The behavioral experiments showed that the
      delay detection threshold was extended and that the probability curve for delay
      detection was less steep in apraxic patients compared to controls (pseudo-apraxic
      patients and unaffected patients), only for the active movement condition, and
      not for the tactile and passive movement conditions. Furthermore, the severity of
      apraxia was significantly correlated with the delay detection threshold and the
      steepness of the probability curve in the active movement condition. These
      results indicated that multisensory (i.e., visual, tactile, and proprioception)
      feedback was normally temporally integrated, but motor prediction and visual
      feedback were not correctly temporally integrated in apraxic patients. That is,
      apraxic patients had difficulties with visuo-motor temporal integration. Lesion
      analyses revealed that both apraxia and the distortion of visuo-motor temporal
      integration were associated with lesions in the fronto-parietal motor network,
      including the left inferior parietal lobule and left inferior frontal gyrus. We
      suppose that damage to the left inferior fronto-parietal network could cause
      deficits in motor prediction for visuo-motor temporal integration, but not for
      sensory-sensory (visuo-tactile and visuo-proprioception) temporal integration,
      leading to the distortion of visuo-motor temporal integration in patients with
      apraxia.

PMID- 30210438
TI  - White Matter Tissue Quantification at Low b-Values Within Constrained Spherical
      Deconvolution Framework.
AB  - In the last decades, a number of Diffusion Weighted Imaging (DWI) based
      techniques have been developed to study non-invasively human brain tissues,
      especially white matter (WM). In this context, Constrained Spherical
      Deconvolution (CSD) is recognized as being able to accurately characterize water
      molecules displacement, as they emerge from the observation of MR diffusion
      weighted (MR-DW) images. CSD is suggested to be applied on MR-DW datasets
      consisting of b-values around 3,000 s/mm2 and at least 45 unique diffusion
      weighting directions. Below such technical requirements, Diffusion Tensor Imaging
      (DT) remains the most widely accepted model. Unlike CSD, DTI is unable to resolve
      complex fiber geometries within the brain, thus affecting related tissues
      quantification. In addition, thanks to CSD, an index called Apparent Fiber
      Density (AFD) can be measured to estimate intra-axonal volume fraction within WM.
      In standard clinical settings, diffusion based acquisitions are well below such
      technical requirements. Therefore, in this study we wanted to extensively compare
      CSD and DTI model outcomes on really low demanding MR-DW datasets, i.e.,
      consisting of a single shell (b-value = 1,000 s/mm2) and only 30 unique diffusion
      encoding directions. To this end, we performed deterministic and probabilistic
      tractographic reconstruction of two major WM pathways, namely the Corticospinal
      Tract and the Arcuate Fasciculus. We estimated and analyzed tensor based features
      as well as, for the first time, AFD interpretability in our data. By performing
      multivariate statistics and tract-based ROI analysis, we demonstrate that WM
      quantification is affected by both the diffusion model and threshold applied to
      noisy tractographic maps. Consistently with existing literature, we showed that
      CSD outperforms DTI even in our scenario. Most importantly, for the first time we
      address the problem of accuracy and interpretation of AFD in a low-demanding DW
      setup, and show that it is still a biological meaningful measure for the analysis
      of intra-axonal volume even in clinical settings.

PMID- 30210439
TI  - MRI Markers and Functional Performance in Patients With CIS and MS: A Cross
      Sectional Study.
AB  - Introduction: Brain atrophy is a widely accepted marker of disease severity with
      association to clinical disability in multiple sclerosis (MS). It is unclear to
      which extent this association reflects common age effects on both atrophy and
      function. Objective: To explore how functional performance in gait, upper
      extremities and cognition is associated with brain atrophy in patients with
      Clinically Isolated Syndrome (CIS) and relapsing-remitting MS (RRMS), controlling
      for effects of age and sex. Methods: In 27 patients with CIS, 59 with RRMS (EDSS
      <=3) and 63 healthy controls (HC), 3T MRI were analyzed for T2 lesion count
      (T2C), volume (T2V) and brain volumes [normalized brain volume (NBV), gray matter
      volume (NGMV), white matter volume (NWMV), thalamic volume (NThalV)]. Functional
      performance was measured with short maximum walking speed (SMSW speed), 9-hole
      peg test (9HPT) and symbol digit modalities test (SDMT). Linear regression models
      were created for functional variables with stepwise inclusion of age, sex and MR
      imaging markers. Results: CIS differed from HC only in T2C and T2V. RRMS differed
      from HC in NBV, NGMV and NThalV, T2C and T2V, but not in NWMV. A strong
      association with age was seen in HC, CIS and RRMS groups for NBV (r = -0.5 to 
      0.6) and NGMV (r = -0.6 to -0.8). Associations with age were seen in HC and RRMS
      but not CIS for NThalV (r = -0.3; r = -0.5), T2C (rs = 0.3; rs = 0.2) and T2V (rs
      = 0.3; rs = 0.3). No effect of age was seen on NWMV. Correlations of functional
      performance with age in RRMS were seen for SMSW speed, 9HPTand SDMT (r = -0.27 to
      -0.46). Regression analyses yielded significant models only in the RRMS group for
      9HPT, SMSW speed and EDSS. These included NBV, NGMV, NThalV, NWMV, logT2V, age
      and sex as predictors. NThalV was the only MRI variable predicting a functional
      measure (9HPTr) with a higher standardized beta than age and sex (R2 = 0.36, p <
      1e-04). Conclusion: Thalamic atrophy was a stronger predictor of hand function
      (9HPT) in RRMS, than age and sex. This underlines the clinical relevance of
      thalamic atrophy and the relevance of hand function as a clinical marker even in
      mildly disabled patients.

PMID- 30210440
TI  - Microvascular Parameters Help to Predict Stroke Risk in the Asian Diabetic
      Population in Taiwan: A Population Based Case-Control Study.
AB  - Intensive glycemic control has not shown consistent findings in stroke prevention
      for diabetes patients, particularly for those with microvascular complications.
      This case-control study evaluates the risks of stroke in Asian diabetic
      population with microvascular complications. From the insurance claims of Taiwan,
      we identified 67,426 type 2 diabetic mellitus (DM) patients with newly diagnosed
      stroke in 2000-2011 and 134,852 randomly selected controls with DM but without
      stroke, matched by sex, age, and number of years since diagnosis of DM.
      Conditional logistic regression analysis measured crude odds ratios (OR) and
      adjusted odds ratio (aOR) of stroke and 95% confidence intervals (CI) for
      associations with demographic status, comorbidities, and microvascular
      complications: retinopathy (RetP), neuropathy (NeuP) or nephropathy (NepP). The
      aOR of stroke increased significantly associated with each complication: 1.47
      with RetP, 1.73 with NeuP and 1.23 with NepP. The risk increased further when
      there was a combination of complications. The overall aOR of stroke was 2.83 (95%
      CI 2.58-3.09) for stroke patients with 3 microvascular complications. The
      corresponding aOR of ischemic stroke was 2.64 (95% CI 2.39-2.91) and that of
      hemorrhagic stroke was 4.12 (95% CI 3.25-5.22). The number of microvascular
      complications positively correlated to the prevalence of comorbidity (p < 0.01).
      This study suggests that microvascular complications are significant stroke
      predictors, with a greater involvement for ischemic stroke than for hemorrhagic
      stroke. Multiple microvascular complications interactively increase the stroke
      risk. Our study contributes to the identification of high-risk subjects for
      stroke prevention and adequate glycemic control.

PMID- 30210436
TI  - Deep Brain Stimulation and L-DOPA Therapy: Concepts of Action and Clinical
      Applications in Parkinson's Disease.
AB  - L-DOPA is still the most effective pharmacological therapy for the treatment of
      motor symptoms in Parkinson's disease (PD) almost four decades after it was first
      used. Deep brain stimulation (DBS) is a safe and highly effective treatment
      option in patients with PD. Even though a clear understanding of the mechanisms
      of both treatment methods is yet to be obtained, the combination of both
      treatments is the most effective standard evidenced-based therapy to date. Recent
      studies have demonstrated that DBS is a therapy option even in the early course
      of the disease, when first complications arise despite a rigorous adjustment of
      the pharmacological treatment. The unique feature of this therapeutic approach is
      the ability to preferentially modulate specific brain networks through the choice
      of stimulation site. The clinical effects have been unequivocally confirmed in
      recent studies; however, the impact of DBS and the supplementary effect of L-DOPA
      on the neuronal network are not yet fully understood. In this review, we present
      emerging data on the presumable mechanisms of DBS in patients with PD and discuss
      the pathophysiological similarities and differences in the effects of DBS in
      comparison to dopaminergic medication. Targeted, selective modulation of brain
      networks by DBS and pharmacodynamic effects of L-DOPA therapy on the central
      nervous system are presented. Moreover, we outline the perioperative algorithms
      for PD patients before and directly after the implantation of DBS electrodes and
      strategies for the reduction of side effects and optimization of motor and non
      motor symptoms.

PMID- 30210442
TI  - Impact of the Thrombectomy Trials on the Management and Outcome of Large Vessel
      Stroke: Data From the Lyon Stroke Center.
AB  - Introduction: Randomized trials (RT) have recently validated the superiority of
      thrombectomy over standard medical care, including intravenous thrombolysis
      (IVT). However, data on their impact on routine clinical care remains scarce.
      Methods: Using a prospective observational registry, we assessed: (1) the
      clinical and radiological characteristics of all consecutive patients treated
      with thrombectomy; (2) the outcome of all patients with M1 occlusion (treated
      with thrombectomy or IVT alone). Two periods were compared: before (2013-2014)
      and after (2015-2016) the publication of RT. Results: Endovascular procedures
      significantly increased between the two periods (N = 82 vs. 314, p < 0.0001). In
      2015-2016, patients were older (median [IQR]: 69 [57-80]; vs. 66 [53-74]; p =
      0.008), had shorter door-to-clot times (69 [47-95]; vs. 110 [83-155]; p < 0.0001)
      resulting in a trend toward shorter delay from symptom onset to reperfusion (232
      [185-300]; vs. 250 [200-339]; p = 0.1), with higher rates of reperfusion (71 vs.
      48%; p = 0.0001). Conversely, no significant differences in baseline NIHSS
      scores, ASPECTS, delay to IVT or intracranial hemorrhage were found. In 2015
      2016, patients with M1 occlusion were treated with thrombectomy more often than
      in 2013-2014 (87 vs. 32%, respectively; p < 0.0001), with a significant
      improvement in clinical outcome (shift analysis, lower modified Rankin scale
      scores: OR = 1.68; 95% CI: 1.10-2.57; p = 0.017). Conclusion: Following the
      publication of RT, thrombectomy was rapidly implemented with significant
      improvements in intrahospital delay and reperfusion rates. Treatment with
      thrombectomy increased with better clinical outcomes in patients with M1
      occlusion.

PMID- 30210443
TI  - Arterial Stiffness and Cerebral Small Vessel Disease.
AB  - Background and Objective: Studies on relations between arterial stiffness and
      full spectrum of radiological features of cerebral small vessel disease (CSVD)
      are scarce. We aim to investigate the association of arterial stiffness with
      lacunes, white matter hyperintensities (WMH), microbleeds (CMBs), dilated
      perivascular spaces (PVS), and brain atrophy in a community-based sample.
      Methods: A total of 953 participants (55.7 +/- 9.4 years) who underwent brachial
      ankle pulse wave velocity (baPWV) and brain magnetic resonance imaging were
      included. Lacunes, CMBs, and PVS were visually rated. Brain structure and WMH
      were automatically segmented. Brain parenchyma fraction (BPF), a surrogate index
      of brain atrophy, was calculated as a ratio of brain parenchyma volume to total
      intracranial volume. Multivariable logistic and linear regressions were used to
      investigate the associations between baPWV and CSVD. Subsequently, we explored
      these associations in strata of age. Results: Increased baPWV was associated with
      severe PVS in white matter (OR, 1.09; 95%CI, 1.01-1.17; p = 0.022), larger WMH
      volume (beta, 0.08; 95%CI, 0.04-0.12; p < 0.001), lower BPF (beta, -0.09; 95%CI, 
      0.15- -0.03; p = 0.007), and marginally associated with strictly lobar CMBs (OR,
      1.11; 95%CI, 1.00-1.23; p = 0.055), but not with lacunes. WMH volume mediated the
      relation between baPWV and BPF. In age subgroup analysis, the association of
      baPWV with PVS in white matter was stronger among those aged <55 years, whereas
      the association with brain atrophy was more prominent among those aged >=55
      years. Increased baPWV was associated with larger WMH volume in both younger and
      older individuals. Conclusions: Increased arterial stiffness was associated with
      most of imaging markers of CSVD, including PVS in white matter, larger WMH
      volume, strictly lobar CMBs, and brain atrophy, but not lacunes. The mechanisms
      underlying these associations and their potential clinical significances warrant
      further investigations.

PMID- 30210444
TI  - Influence of Admission Blood Glucose in Predicting Outcome in Patients With
      Spontaneous Intracerebral Hematoma.
AB  - Background and Aims: Hyperglycemia or elevated blood glucose levels have been
      associated with poor outcomes in patients with ischemic stroke yet control of
      hyperglycemia has not resulted in good outcomes. High admission blood glucose
      (ABG) values have been mitigated by other poor prognosticators like large
      hematoma volume, intraventricular extension (IVE) of hematoma and poor GCS. The
      aim of this study was to evaluate the effects of blood glucose levels at
      admission, on mortality and functional outcomes at discharge and 3 months follow
      up. Methods: This was a retrospective observational study conducted at a tertiary
      care. Patients with spontaneous SICH were enrolled from a prospective SICH
      register maintained at our hospital. Blood glucose values were recorded on
      admission. Patients with traumatic hematomas, vascular malformations, aneurysms,
      and coagulation abnormalities were excluded from our study. Results: A total of
      510 patients were included in the study. We dichotomised our cohort into two
      groups, group A with ABG>160 mg/dl and group B with ABG<160 mg/dl. Mean blood
      glucose levels in these two groups were 220.73 mg/dl and 124.37 mg/dl
      respectively, with group A having twice the mortality. mRS at discharge and 3
      months was better in Group B (p <= 0.001) as compared to Group A. Age, GCS,
      volume of hematoma, ABG, IVE and Hydrocephalus were significant predictors of
      mortality and poor outcome on univariate analysis with a p < 0.05. The
      relationship between ABG and mortality (P = 0.249, 95% CI 0.948-1.006) and
      outcome (P = 0.538, 95% CI 0.997-1.005) failed to reach statistical significance
      on multivariate logistic regression. Age, Volume of hematoma and GCS were
      stronger predictors of mortality and morbidity. Conclusion: Admission blood
      glucose levels was not an independent predictor of mortality in our study when
      adjusted with age, GCS, and hematoma volume. The effect of high ABG on SICH
      outcome is probably multifactorial and warrants further research.

PMID- 30210446
TI  - Assessment of the Efficacy of ReoGo-J Robotic Training Against Other
      Rehabilitation Therapies for Upper-Limb Hemiplegia After Stroke: Protocol for a
      Randomized Controlled Trial.
AB  - Background: Stroke patients experience chronic hemiparesis in their upper
      extremities leaving negative effects on quality of life. Robotic therapy is one
      method to recover arm function, but its research is still in its infancy.
      Research questions of this study is to investigate how to maximize the benefit of
      robotic therapy using ReoGo-J for arm hemiplegia in chronic stroke patients.
      Methods: Design of this study is a multi-center parallel group trial following
      the prospective, randomized, open-label, blinded endpoint (PROBE) study model.
      Participants and setting will be 120 chronic stroke patients (over 6 months post
      stroke) will be randomly allocated to three different rehabilitation protocols.
      In this study, the control group will receive 20 min of standard rehabilitation
      (conventional occupational therapy) and 40 min of self-training (i.e., sanding,
      placing and stretching). The robotic therapy group will receive 20 min of
      standard rehabilitation and 40 min of robotic therapy using ReoGo(r)-J device.
      The combined therapy group will receive 40 min of robotic therapy and 20 min of
      constraint-induced movement therapy (protocol to improve upper-limb use in ADL
      suggests). This study employs the Fugl-Meyer Assessment upper-limb score (primary
      outcome), other arm function measures and the Stroke Impact Scale score will be
      measured at baseline, 5 and 10 weeks of the treatment phase. In analysis of this
      study, we use the mixed effects model for repeated measures to compare changes in
      outcomes between groups at 5 and 10 Weeks. The registration number of this study
      is UMIN000022509. Conclusions: This study is a feasible, multi-site randomized
      controlled trial to examine our hypothesis that combined training protocol could
      maximize the benefit of robotic therapy and best effective therapeutic strategy
      for patients with upper-limb hemiparesis.

PMID- 30210445
TI  - Diagnostic Performance of Neurofilaments in Chinese Patients With Amyotrophic
      Lateral Sclerosis: A Prospective Study.
AB  - Several studies have attempted to reduce diagnostic delay and identify biomarkers
      for drug development in amyotrophic lateral sclerosis (ALS). In this study, we
      aimed to evaluate the diagnostic accuracy for ALS of cerebrospinal fluid (CSF)
      neurofilament (Nf), Tau protein, and inflammatory factors such as interleukin
      (IL)-2, IL-6, IL-10, IL-15, and granulocyte-macrophage colony-stimulating factor
      (GMCSF) in Chinese patients. Our prospective study measured the concentration of
      phosphorylated Nf heavy chain (pNfH), Nf light chain (NfL), Tau, pTau, and
      inflammatory factors in the CSF of 85 patients. Detailed clinical data and
      laboratory, neuroimaging, and neurophysiological findings were recorded. The
      concentrations of pNfH and NfL were higher in the ALS group than in the control
      group. At the 1104 pg/mL pNfH cutoff, the specificity was 68.8%, the sensitivity
      100%, and the area under the curve (AUC) 0.907. At the 1,139 pg/mL NfL cutoff,
      the specificity was 56.3%, the sensitivity 96.2%, and the AUC 0.775. There was no
      significant difference in the concentrations of Tau, pTau, IL-2, IL-6, IL-10, IL
      15, and GMCSF between the ALS and control groups (p > 0.05). In the ALS group,
      the concentration of pNfH in the CSF was correlated with disease duration (r = 
      0.475, p < 0.001). This is the first prospective study to confirm the diagnostic
      value of Nf for ALS in Chinese patients.

PMID- 30210441
TI  - Drug Seeking and Relapse: New Evidence of a Role for Orexin and Dynorphin Co
      transmission in the Paraventricular Nucleus of the Thalamus.
AB  - The long-lasting vulnerability to relapse remains the main challenge for the
      successful treatment of drug addiction. Neural systems that are involved in
      processing natural rewards and drugs of abuse overlap. However, neuroplasticity
      that is caused by drug exposure may be responsible for maladaptive, compulsive,
      and addictive behavior. The orexin (Orx) system participates in regulating
      numerous physiological processes, including energy metabolism, arousal, and
      feeding, and is recruited by drugs of abuse. The Orx system is differentially
      recruited by drugs and natural rewards. Specifically, we found that the Orx
      system is more engaged by drugs than by non-drugs, such as sweetened condensed
      milk (SCM) or a glucose saccharin solution (GSS), in an operant model of reward
      seeking. Although stimuli (S+) that are conditioned to cocaine (COC), ethanol,
      and SCM/GSS equally elicited reinstatement, Orx receptor blockade reversed
      conditioned reinstatement for drugs vs. non-drugs. Moreover, the hypothalamic
      recruitment of Orx cells was greater in rats that were tested with the COC S+ vs.
      SCM S+, indicating of a preferential role for the Orx system in perseverative,
      compulsive-like COC seeking and not behavior that is motivated by palatable food.
      Accumulating evidence indicates that the paraventricular nucleus of the thalamus
      (PVT), which receives major Orx projections, mediates drug-seeking behavior. All
      Orx neurons contain dynorphin (Dyn), and Orx and Dyn are co-released. In the VTA,
      they play opposing roles in reward and motivation. To fully understand the
      physiological and behavioral roles of Orx transmission in the PVT, one important
      consideration is that Orx neurons that project to the PVT may co-release Orx with
      another peptide, such as Dyn. The PVT expresses both Orx receptors and kappa
      opioid receptors, suggesting that Orx and Dyn act in tandem when released in the
      PVT, in addition to the VTA. The present review discusses recent findings that
      suggest the maladaptive recruitment of Orx/Dyn-PVT neurotransmission by drugs of
      abuse vs. a highly palatable food reward.

PMID- 30210447
TI  - Imatinib Inhibits GH Secretion From Somatotropinomas.
AB  - Background: Imatinib, a tyrosine kinase inhibitor, causes growth failure in
      children with chronic myeloid leukemia probably by targeting the growth hormone
      (GH)/insulin like growth factor-1 (IGF-1) axis. We aim to explore the imatinib
      targets expression in pituitary adenomas and study the effect of imatinib on GH
      secretion in somatotropinoma cells and GH3 cell line. Materials and Methods: The
      expression pattern of imatinib's targets (c-kit, VEGF, and PDGFR-alpha/beta) was
      studied using immunohistochemistry and immunoblotting 157 giant (>=4 cm)
      pituitary adenomas (121 non-functioning pituitary adenomas, 32 somatotropinomas,
      and four prolactinomas) and compared to normal pituitary (n = 4) obtained at
      autopsy. The effect imatinib on GH secretion, cell viability,
      immunohistochemistry, electron microscopy, and apoptosis was studied in primary
      culture of human somatotropinomas (n = 20) and in rat somato-mammotroph GH3 cell
      line. A receptor tyrosine kinase array was applied to human samples to identify
      altered pathways. Results: Somatotropinomas showed significantly higher
      immunopositivity for c-kit and platelet-derived growth factor receptor-beta
      (PDGFR-beta; P < 0.009 and P < 0.001, respectively), while staining for platelet
      derived growth factor receptor-alpha (PDGFR-alpha) and vascular endothelial
      growth factor (VEGF) revealed a weaker expression (P < 0.001) compared to normal
      pituitary. Imatinib inhibited GH secretion from both primary culture (P < 0.01)
      and GH3 cells (P < 0.001), while it did not affect cell viability and apoptosis.
      The receptor tyrosine kinase array showed that imatinib inhibits GH signaling via
      PDGFR-beta pathway. Conclusion: Imatinib inhibits GH secretion in somatotropinoma
      cells without affecting cell viability and may be used as an adjunct therapy for
      treating GH secreting pituitary adenomas.

PMID- 30210448
TI  - Differentiation of Testis Xenografts in the Prepubertal Marmoset Depends on the
      Sex and Status of the Mouse Host.
AB  - This study investigates the effects of the endocrine milieu of immunodeficient
      mouse host (intact vs. castrated male, intact male vs. intact female) on
      prepubertal marmoset (Callithrix jacchus) testicular xenografts. Previous
      marmoset xenografting studies used castrated nude mouse hosts which did not
      support efficient graft survival and maturation. Due to the distinct endocrine
      milieu in marmosets with a deletion of exon 10 in the LH receptor, we wanted to
      explore whether the most efficient xenograft development occurs in intact male
      mouse hosts compared to intact females or castrated males. We xenografted freshly
      isolated tissue from prepubertal marmosets (age range 4-6 months) into the back
      skin of three groups of nude mice (intact male, castrated male, and intact
      female). We collected serum for endocrine determinations and grafts after 20
      weeks and determined hormonal/reproductive status, graft survival, somatic cell
      development and initiation of germ cell differentiation. Graft development,
      tubular integrity, and germ cell differentiation status in the grafts retrieved
      from different hosts was scored by morphometric analysis. The influence of the
      different endocrine status was compared between groups of hosts. Endocrine
      readouts and histological endpoints in xenografts substantiate that grafts were
      exposed to different microenvironments and responded with host specific
      developmental patterns. The intact male hosts supported the most significant
      progression of germ cell development. Our data provide evidence for the important
      role of the host milieu on survival and differentiation of marmoset xenografts.
      The xenografting model offers innovative avenues to exploit development and
      endocrine effects in the primate marmoset testis using limited numbers of non
      human primates for the experimental settings.

PMID- 30210449
TI  - Prolactin Variants in Human Pituitaries and Pituitary Adenomas Identified With
      Two-Dimensional Gel Electrophoresis and Mass Spectrometry.
AB  - Human prolactin (hPRL) plays multiple roles in growth, metabolism, development,
      reproduction, and immunoregulation, which is an important protein synthesized in
      a pituitary. Two-dimensional gel electrophoresis (2DE) is an effective method in
      identity of protein variants for in-depth insight into functions of that protein.
      2DE, 2DE-based PRL-immunoblot, mass spectrometry, and bioinformatics were used to
      analyze hPRL variants in human normal (control; n = 8) pituitaries and in five
      subtypes of pituitary adenomas [NF- (n = 3)-, FSH+ (n = 3)-, LH+ (n = 3)-,
      FSH+/LH+ (n = 3)-, and PRL+ (n = 3)-adenomas]. Six hPRL variants were identified
      with different isoelectric point (pI)-relative molecular mass (Mr ) distribution
      on a 2DE pattern, including variants V1 (pI 6.1; 26.0 kDa), V2 (pI 6.3; 26.4
      kDa), V3 (pI 6.3; 27.9 kDa), V4 (pI 6.5; 26.1 kDa), V5 (pI 6.8; 25.9 kDa), and V6
      (pI 6.7; 25.9 kDa). Compared to controls, except for variants V2-V6 in PRL
      adenomas, V2 in FSH+-adenomas, and V3 in NF--adenomas, the other PRL variants
      were significantly downregulated in each subtype of pituitary adenomas. Moreover,
      the pattern of those six PRL variants was significantly different among five
      subtypes of pituitary adenomas relative to control pituitaries. Different hPRL
      variants might be involved in different types of PRL receptor-signaling pathways
      in a given condition. Those findings clearly revealed the existence of six hPRL
      variants in human pituitaries, and the pattern changes of six hPRL variants among
      different subtypes of pituitary adenomas, which provide novel clues to further
      study the functions, and mechanisms of action, of hPRL in human pituitary and in
      PRL-related diseases, and the potential clinical value in pituitary adenomas.

PMID- 30210450
TI  - High-Intensity Interval Training Is Equivalent to Moderate-Intensity Continuous
      Training for Short- and Medium-Term Outcomes of Glucose Control, Cardiometabolic
      Risk, and Microvascular Complication Markers in Men With Type 2 Diabetes.
AB  - We sought to determine the efficacy of 12 weeks high-intensity interval training
      (HIIT), compared to moderate-intensity continuous training (MICT) on glucose
      control, cardiometabolic risk and microvascular complication markers in men
      living with type 2 diabetes (T2D). Both modalities were combined with resistance
      training (RT). Additionally, the study aimed to determine the medium-term
      durability of effects. After a 12-week, thrice weekly, training intervention
      incorporating either MICT+RT (n = 11) or HIIT+RT (n = 12), the study concluded
      with a 6-month follow-up analysis. The middle-aged study participants were obese,
      had moderate duration T2D and were taking multiple medications including insulin,
      statins and beta-blockers. Participants, randomized via the method of
      minimization, performed MICT (progressing to 26-min at 55% maximum estimated
      workload [eWLmax]) or HIIT (progressing to two variations in which twelve 1-min
      bouts at 95% eWLmax interspersed with 1-min recovery bouts, alternated with eight
      30-s bouts at 120% eWLmax interspersed with 2:15 min recovery bouts) under
      supervision at an exercise physiology facility. To account for fixed and random
      effects within the study sample, mixed-effect models were used to determine the
      significance of change following the intervention and follow-up phases and to
      evaluate group*time interactions. Beyond improvements in aerobic capacity (P <
      0.001) for both groups, both training modalities elicited similar group*time
      interactions (P > 0.05) while experiencing benefits for glycated hemoglobin
      (HbA1c; P = 0.01), subcutaneous adiposity (P < 0.001), and heart rate variability
      (P = 0.02) during the 12-week intervention. Adiposity (P < 0.001) and aerobic
      capacity (P < 0.001) were significantly maintained in both groups at the 6-month
      follow-up. In addition, during the intervention, participants in both MICT+RT and
      HIIT+RT experienced favorable reductions in their medication usage. The study
      reported the inter-individual variability of change within both groups, the
      exaggerated acute physiological responses (using exercise termination indicators)
      that occurred during the interventions as well as the incidence of precautionary
      respite afforded in such a study sample. To reduce hyperglycaemia, and prevent
      further deterioration of cardiometabolic risk and microvascular complication
      markers (in both the short- and medium-term), future strategies that integrate
      the adoption and maintenance of physical activity as a cornerstone in the
      treatment of T2M for men should (cognisant of appropriate supervision) include
      either structured MICT+RT, or HIIT+RT. Clinical Trials Registration Number:
      ACTRN12617000582358 http://www.anzctr.org.au/default.aspx.

PMID- 30210452
TI  - Life Under Hypoxia Lowers Blood Glucose Independently of Effects on Appetite and
      Body Weight in Mice.
AB  - Blood glucose and the prevalence of diabetes are lower in mountain than lowland
      dwellers, which could among other factors be due to reduced oxygen availability.
      To investigate metabolic adaptations to life under hypoxia, male mice on high fat
      diet (HFD) were continuously maintained at 10% O2. At variance to preceding
      studies, the protocol was designed to dissect direct metabolic effects from such
      mediated indirectly via hypoxia-induced reductions in appetite and weight gain.
      This was achieved by two separate control groups on normal air, one with free
      access to HFD, and one fed restrictedly in order to obtain a weight curve
      matching that of hypoxia-exposed mice. Comparable body weight in restrictedly fed
      and hypoxic mice was achieved by similar reductions in calorie intake (-22%) and
      was associated with parallel effects on body composition as well as on
      circulating insulin, leptin, FGF-21, and adiponectin. Whereas the effects of
      hypoxia on the above parameters could thus be attributed entirely to blunted
      weight gain, hypoxia improved glucose homeostasis in part independently of body
      weight (fasted blood glucose, mmol/l: freely fed control, 10.2 +/- 0.7; weight
      matched control, 8.0 +/- 0.3; hypoxia, 6.8 +/- 0.2; p < 0.007 each; AUC in the
      glucose tolerance test, mol/l*min: freely fed control, 2.54 +/- 0.15; weight
      matched control, 1.86 +/- 0.08; hypoxia, 1.67 +/- 0.05; p < 0.05 each). Although
      counterintuitive to lowering of glycemia, insulin sensitivity appeared to be
      impaired in animals adapted to hypoxia: In the insulin tolerance test, hypoxia
      treated mice started off with lower glycaemia than their weight-matched controls
      (initial blood glucose, mmol/l: freely fed control, 11.5 +/- 0.7; weight-matched
      control, 9.4 +/- 0.3; hypoxia, 8.1 +/- 0.2; p < 0.02 each), but showed a weaker
      response to insulin (final blood glucose, mmol/l: freely fed control, 7.0 +/-
      0.3; weight-matched control, 4.5 +/- 0.2; hypoxia, 5.5 +/- 0.3; p < 0.01 each).
      Furthermore, hypoxia weight-independently reduced hepatic steatosis as normalized
      to total body fat, suggesting a shift in the relative distribution of
      triglycerides from liver to fat (mg/g liver triglycerides per g total fat mass:
      freely fed control, 10.3 +/- 0.6; weight-matched control, 5.6 +/- 0.3; hypoxia,
      4.0 +/- 0.2; p < 0.0004 each). The results show that exposure of HFD-fed mice to
      continuous hypoxia leads to a unique metabolic phenotype characterized by
      improved glucose homeostasis along with evidence for impaired rather than
      enhanced insulin sensitivity.

PMID- 30210451
TI  - Nesfatin-1 Regulates Feeding, Glucosensing and Lipid Metabolism in Rainbow Trout.
AB  - Nesfatin-1 is an 82 amino acid peptide that has been involved in a wide variety
      of physiological functions in both mammals and fish. This study aimed to
      elucidate the role of nesfatin-1 on rainbow trout food intake, and its putative
      effects on glucose and fatty acid sensing systems. Intracerebroventricular
      administration of 25 ng/g nesfatin-1 resulted in a significant inhibition of
      appetite, likely mediated by the activation of central POMC and CART. Nesfatin-1
      stimulated the glucosensing machinery (changes in sglt1, g6pase, gsase, and gnat3
      mRNA expression) in the hindbrain and hypothalamus. Central fatty acid sensing
      mechanisms were unaltered by nesfatin-1, but this peptide altered the expression
      of mRNAs encoding factors regulating lipid metabolism (fat/cd36, acly, mcd, fas,
      lpl, pparalpha, and ppargamma), suggesting that nesfatin-1 promotes lipid
      accumulation in neurons. In the liver, intracerebroventricular nesfatin-1
      treatment resulted in decreased capacity for glucose use and lipogenesis, and
      increased the potential of fatty acid oxidation. Altogether, the present results
      demonstrate that nesfatin-1 is involved in the homeostatic regulation of food
      intake and metabolism in fish.

PMID- 30210453
TI  - The Androgen Receptor in Breast Cancer.
AB  - Breast cancer (BC) is a hormone-related tumor. Despite the progress in BC
      therapy, this disease still remains the most common cancer amongst women around
      the world. This is likely due to the amazing BC heterogeneity. Accumulating
      evidence suggests a role for androgen signaling in BC. Nevertheless, a precise
      understanding of the mechanism of androgen action in this disease remains a
      challenging puzzle. Androgen receptor (AR) is often expressed in BC and several
      studies suggest that its role depends on the tumor microenvironment as well as
      the relative levels of circulating estrogens and androgens. However, the AR
      function in BC is still conflicting. Although AR expression is often associated
      with a favorable prognosis in EREstradiol Receptoralpha-positive (ERalpha +) BC,
      many findings suggest that, in some instances, high levels of AR can contribute
      to the therapy-resistance. Again, in ERalpha negative BC (ERalpha -), AR is
      mainly expressed in tumors with apocrine differentiation and a lower Nottingham
      grade. Moreover, AR stimulates cellular proliferation in triple negative breast
      cancer (ERalpha -, PgR -, and HER-2-Neu -). This finding is substantiated by the
      observation that high levels of circulating androgens are associated with an
      increased risk of developing BC in post-menopausal woman. Treatment of ERalpha-
      BC with AR antagonists, such as bicalutamide or enzalutamide, reduces, indeed,
      the tumor growth. In this review, we will analyze the putative role of AR in BC.
      Emerging therapies based on the use of new agonists or antagonists or inhibitors
      will be here discussed.

PMID- 30210454
TI  - Association of PON2 Gene Polymorphisms (Ser311Cys and Ala148Gly) With the Risk of
      Developing Type 2 Diabetes Mellitus in the Chinese Population.
AB  - Background: The association between paraoxonase 2 (PON2) gene polymorphisms and
      type 2 diabetes mellitus (T2DM) has been extensively investigated in the Chinese
      population with conflicting results. In this study, we systematically evaluated
      the association between PON2 Ser311Cys and Ala148Gly polymorphisms and T2DM risk
      by pooling all relevant studies. Methods: We searched PubMed, Embase, CNKI, and
      Wanfang databases for the studies. The strength of association was determined by
      the allelic, homozygous, heterozygous, recessive, and dominant genetic models and
      measured as odds ratio (OR) and 95% confidence interval (CI), under fixed- or
      random-effect models. Results: There was no significant association between PON2
      Ser311Cys polymorphism and T2DM under any of the genetic models: allelic (OR =
      1.06, 95% CI = 0.77-1.45; P = 0.721), heterozygous (OR = 1.13, 95% CI = 0.87
      1.45; P = 0.362), dominant (OR = 1.10, 95% CI = 0.80-1.51; P = 0.562), recessive
      (OR = 0.87, 95% CI = 0.48-1.58; P = 0.648), homozygous (OR = 0.94, 95% CI = 0.47
      1.89; P = 0.865). Similarly, no significant association was found in PON2
      Arg148Gly polymorphism under any of the models: allelic (OR = 1.17, 95% CI = 0.91
      1.50; P = 0.218), heterozygous (OR = 1.28, 95% CI = 0.94-1.74; P = 0.117),
      dominant (OR = 1.25, 95% CI = 0.93-1.67; P = 0.142), recessive (OR = 0.99, 95% CI
      = 0.52-1.88; P = 0.973), homozygous (OR = 1.08, 95% CI = 0.57-2.07; P = 0.808).
      Conclusions: The PON2 Ser311Cys and Ala148Gly polymorphisms were not associated
      with the risk of developing T2DM in the Chinese population.

PMID- 30210456
TI  - High-Throughput Sequencing and the Viromic Study of Grapevine Leaves: From the
      Detection of Grapevine-Infecting Viruses to the Description of a New
      Environmental Tymovirales Member.
AB  - In the past decade, high-throughput sequencing (HTS) has had a major impact on
      virus diversity studies as well as on diagnosis, providing an unbiased and more
      comprehensive view of the virome of a wide range of organisms. Rather than the
      serological and molecular-based methods, with their more "reductionist" view
      focusing on one or a few known agents, HTS-based approaches are able to give a
      "holistic snapshot" of the complex phytobiome of a sample of interest. In
      grapevine for example, HTS is powerful enough to allow for the assembly of
      complete genomes of the various viral species or variants infecting a sample of
      known or novel virus species. In the present study, a total RNAseq-based approach
      was used to determine the full genome sequences of various grapevine fanleaf
      virus (GFLV) isolates and to analyze the eventual presence of other viral agents.
      From four RNAseq datasets, a few complete grapevine-infecting virus and viroid
      genomes were de-novo assembled: (a) three GFLV genomes, 11 grapevine rupestris
      stem-pitting associated virus (GRSPaV) and six viroids. In addition, a novel
      viral genome was detected in all four datasets, consisting of a single-stranded,
      positive-sense RNA molecule of 6033 nucleotides. This genome displays an
      organization similar to Tymoviridae family members in the Tymovirales order.
      Nonetheless, the new virus shows enough differences to be considered as a new
      species defining a new genus. Detection of this new agent in the original
      grapevines proved very erratic and was only consistent at the end of the growing
      season. This virus was never detected in the spring period, raising the
      possibility that it might not be a grapevine-infecting virus, but rather a virus
      infecting a grapevine-associated organism that may be transiently present on
      grapevine samples at some periods of the year. Indeed, the Tymoviridae family
      comprises isometric viruses infecting a wide range of hosts in different kingdoms
      (Plantae, Fungi, and Animalia). The present work highlights the fact that even
      though HTS technologies produce invaluable data for the description of the
      sanitary status of a plant, in-depth biological studies are necessary before
      assigning a new virus to a particular host in such metagenomic approaches.

PMID- 30210455
TI  - Gut-Brain Neuroendocrine Signaling Under Conditions of Stress-Focus on Food
      Intake-Regulatory Mediators.
AB  - The gut-brain axis represents a bidirectional communication route between the gut
      and the central nervous system comprised of neuronal as well as humoral
      signaling. This system plays an important role in the regulation of
      gastrointestinal as well as homeostatic functions such as hunger and satiety.
      Recent years also witnessed an increased knowledge on the modulation of this axis
      under conditions of exogenous or endogenous stressors. The present review will
      discuss the alterations of neuroendocrine gut-brain signaling under conditions of
      stress and the respective implications for the regulation of food intake.

PMID- 30210457
TI  - Managing the Microbial Community of Marine Fish Larvae: A Holistic Perspective
      for Larviculture.
AB  - The availability of high-quality juveniles is a bottleneck in the farming of many
      marine fish species. Detrimental larvae-microbe interactions are a main reason
      for poor viability and quality in larval rearing. In this review, we explore the
      microbial community of fish larvae from an ecological and eco-physiological
      perspective, with the aim to develop the knowledge basis for microbial
      management. The larvae are exposed to a huge number of microbes from external and
      internal sources in intensive aquaculture, but their relative importance depend
      on the rearing technology used (especially flow-through vs. recirculating
      systems) and the retention time of the water in the fish tanks. Generally, focus
      has been on microbes entering the system, but microbes from growth within the
      system is normally a substantial part of the microbes encountered by larvae.
      Culture independent methods have revealed an unexpected high richness of
      bacterial species associated with larvae, with 100-250 operational taxonomic
      units associated with one individual. The microbiota of larvae changes rapidly
      until metamorphosis, most likely due to changes in the selection pressure in the
      digestive tract caused by changes in host-microbe and microbe-microbe
      interactions. Even though the microbiota of larvae is distinctly different from
      the microbiota of the water and the live food, the microbiota of the water
      strongly affects the microbiota of the larvae. We are in the early phase of
      understanding larvae-microbe interactions in vivo, but some studies with other
      animals than fish emphasize that we so far have underestimated the complexity of
      these interactions. We present examples demonstrating the diversity of these
      interactions. A large variety of microbial management methods exist, focusing on
      non-selective reduction of microbes, selective enhancement of microbes, and on
      improvement of the resistance of larvae against microbes. However, relatively few
      methods have been studied extensively. We believe that there is a lot to gain by
      increasing the diversity of approaches for microbial management. As many
      microbial management methods are perturbations of the microbial community, we
      argue that ecological theory is needed to foresee and test for longer term
      consequences in microbe-microbe and microbe-larvae interactions. We finally make
      some recommendations for future research and development.

PMID- 30210458
TI  - Inoculation of Sinorhizobium saheli YH1 Leads to Reduced Metal Uptake for
      Leucaena leucocephala Grown in Mine Tailings and Metal-Polluted Soils.
AB  - Metalliferous mine tailings have a negative impact on the soil environment near
      mining areas and render cultivable lands infertile. Phytoremediation involving
      the synergism of legume and rhizobia provides a useful technique in tackling this
      issue with cost-effective, environmentally friendly, and easy-to-use features
      under adverse soil conditions. Leucaena leucocephala has been found to build
      symbiotic relationships with native rhizobia in the iron-vanadium-titanium oxide
      (V-Ti magnetite) mine tailing soil. Rhizobia YH1, isolated from the root nodules
      of L. leucocephala, was classified as Sinorhizobium saheli according to
      similarity and phylogenetic analyses of 16S rRNA, housekeeping and nitrogen
      fixation genes. Besides nitrogen fixation, S. saheli YH1 also showed capabilities
      to produce indole-acetic acid (IAA) (166.77 +/- 2.03 mg l-1) and solubilize
      phosphate (104.41 +/- 7.48 mg l-1). Pot culture experiments showed that strain
      YH1 increased the biomass, plant height and root length of L. leucocephala by
      67.2, 39.5 and 27.2% respectively. There was also an average increase in plant N
      (10.0%), P (112.2%) and K (25.0%) contents compared to inoculation-free control.
      The inoculation of YH1 not only reduced the uptake of all metals by L.
      leucocephala in the mine tailings, but also resulted in decreased uptake of Cd by
      up to 79.9% and Mn by up to 67.6% for plants grown in soils contaminated with
      Cd/Mn. It was concluded that S. saheli YH1 possessed multiple beneficial effects
      on L. leucocephala grown in metalliferous soils. Our findings highlight the role
      of S. saheli YH1 in improving plant health of L. leucocephala by reducing metal
      uptake by plants grown in heavy metal-polluted soils. We also suggest the idea of
      using L. leucocephala-S. saheli association for phytoremediation and revegetation
      of V-Ti mine tailings and soils polluted with Cd or Mn.

PMID- 30210459
TI  - FLO Genes Family and Transcription Factor MIG1 Regulate Saccharomyces cerevisiae
      Biofilm Formation During Immobilized Fermentation.
AB  - Saccharomyces cerevisiae immobilization is commonly used for efficient ethanol
      fuel production in industry due to the relatively higher ethanol stress
      resistance of S. cerevisiae in biofilms relative to planktonic cells. The
      mechanisms of biofilm formation and stress resistance, however, remain ambiguous.
      By analyzing biofilm and planktonic cell transcriptomes, this study observed that
      MIG1 (encoding a transcription factor) expression in cells increases during the
      biofilm formation process. To identify the role of MIG1 in yeast biofilm
      formation and the ethanol resistance of these cells, MIG1 was deleted and
      complemented in S. cerevisiae 1308. Results showed the MIG1 deletion mutant
      strain demonstrated weaker biofilm formation ability both on fibers and plastic
      than the wild-type and these could be restored by expressing MIG1 in deletion
      mutant. To verify the ability of MIG1 to regulate the expression of FLO genes,
      which encode adhesions responsible for yeast biofilm formation, FLO gene
      transcription levels were measured via qRT-PCR. Relative to wild-type S.
      cerevisiae, the adhesion genes FLO1, 5, and 9 which also demonstrate increased
      expression in the transcriptome of yeast cells during biofilm formation, but not
      FLO11, were down-regulated in the MIG1 mutant strain. Additionally, the MIG1
      mutant lost a majority of its flocculation ability, which depended on cell-cell
      adhesions and its slightly invasive growth ability, dependent on cell-substrate
      adhesion. Deleting FLO1, 5, and 9 decreased biofilm formation on plastics,
      suggesting these FLO genes contribute to the biofilm formation process alongside
      FLO11. Moreover, the ethanol tolerance of yeast decreased in the MIG1 deletion
      mutant as well as the FLO11 deletion mutant, resulting in reduced biofilm
      formation during fermentation. It remains possible that in the later period of
      fermentation, when ethanol has accumulated, an over-expression of the FLO1, 5,
      and 9 genes regulated by MIG1 would enhanced cell-cell adhesions and thus protect
      cells in the outer layer of biofilms from ethanol, a function primarily dependent
      on cell-cell adhesions. This work offers a possible explanation for how biofilm
      formation is regulated during the immobilized fermentation process, and can
      enhance environmental tolerance in industrial production.

PMID- 30210460
TI  - Role of Ezrin Phosphorylation in HIV-1 Replication.
AB  - Host-cell expression of the ezrin protein is required for CXCR4 (X4)-tropic HIV-1
      infection. Ezrin function is regulated by phosphorylation at threonine-567. This
      study investigates the role of ezrin phosphorylation in HIV-1 infection and
      virion release. We analyzed the effects of ezrin mutations involving substitution
      of threonine-567 by alanine (EZ-TA), a constitutively inactive mutant, or by
      aspartic acid (EZ-TD), which mimics phosphorylated threonine. We also
      investigated the effects of ezrin silencing on HIV-1 virion release using a
      specific siRNA. We observed that X4-tropic HIV-1 vector infection was inhibited
      by expression of the EZ-TA mutant but increased by expression of the EZ-TD
      mutant, suggesting that ezrin phosphorylation in target cells is required for
      efficient HIV-1 entry. Expression of a dominant-negative mutant of ezrin (EZ-N)
      and ezrin silencing in HIV-1 vector-producing cells significantly reduced the
      infectivity of released virions without affecting virion production. This result
      indicates that endogenous ezrin expression is required for virion infectivity.
      The EZ-TD but not the EZ-TA inhibited virion release from HIV-1 vector-producing
      cells. Taken together, these findings suggest that ezrin phosphorylation in
      target cells is required for efficient HIV-1 entry but inhibits virion release
      from HIV-1 vector-producing cells.

PMID- 30210461
TI  - Characterization of ML-005, a Novel Metaproteomics-Derived Esterase.
AB  - A novel gene encoding for a lipolytic enzyme, designated ML-005, was recently
      identified using a functional metaproteomics approach. We heterologously
      expressed this protein in Escherichia coli and biochemically characterized it. ML
      005 exhibited lipolytic activity toward short-chained substrates with the
      preferred substrate being p-nitrophenyl-butyrate, suggesting that ML-005 is an
      esterase. According to homology analysis and site-directed mutagenesis, the
      catalytic triad of the enzyme was identified as Ser-99, Asp-164, and His-191. Its
      optimal pH was determined to be at pH 8. Optimal activity was observed at 45
      degrees C. It also exhibited temperature, pH and salt tolerance. Residual
      relative activity after incubating at 50-60 degrees C for 360 min was above 80%
      of its initial activity. It showed tolerance over a broad range of pH (5-12) and
      retained most of its initial activity. Furthermore, incubating ML-005 in 1 - 5M
      NaCl solution had negligible effect on its activity. DTT, EDTA, and beta
      mercaptoethanol had no significant effect on ML-005's activity. However, addition
      of PMSF led to almost complete inactivation consistent with ML-005 being a serine
      hydrolase. ML-005 remains stable in the presence of a range of metal ions, but
      addition of Cu2+ significantly reduces its relative activity. Organic solvents
      have an inhibitory effect on ML-005, but it retained 21% of activity in 10%
      methanol. SDS had the most pronounced inhibitory effect on ML-005 among all
      detergents tested and completely inactivated it. Furthermore, the Vmax of ML-005
      was determined to be 59.8 MUM/min along with a Km of 137.9 MUM. The kcat of ML
      005 is 26 s-1 and kcat/Km is 1.88 * 105 M-1 s-1.

PMID- 30210463
TI  - Phosphorus and Nitrogen Drive the Seasonal Dynamics of Bacterial Communities in
      Pinus Forest Rhizospheric Soil of the Qinling Mountains.
AB  - The temporal distribution patterns of bacterial communities, as an important
      group in mountain soil, are affected by various environmental factors. To improve
      knowledge regarding the successional seasonal dynamics of the mountain soil
      bacterial communities, the rhizospheric soil of a 30-year-old natural secondary
      Pinus tabulaeformis forest, located in the high-altitude (1900 m a.s.l.) of the
      temperate Qinling Mountains, was sampled and studied during four different
      seasons. The bacterial community composition and structure in the rhizospheric
      soil were studied using an Illumina MiSeq Sequencing platform. Furthermore, the
      edaphic properties and soil enzymatic activities (urease, phosphatase, and
      catalase) were measured in order to identify the main impact factors on the soil
      bacterial community. According to the results, all of the edaphic properties and
      soil enzymatic activities were significantly affected by the seasonal changes,
      except for the C/N ratio. Although the biomasses of soil bacterial communities
      increased during the summer and autumn (warm seasons), their Shannon diversity
      and Pielou's evenness were decreased. Proteobacteria, Acidobacteria,
      Actinobacteria, Planctomycetes, and Bacteroidetes were the predominant bacterial
      groups in all of the soil samples, and the genera of Ktedonobacter, Sphingobium
      as well as an unclassified member of the Ktedonobacteria were the keystone taxa.
      The composition and structure of soil bacterial communities were strongly
      impacted by the edaphic properties, especially the temperature, moisture,
      ammoniacal nitrogen, available phosphorus and total phosphorus which were the
      crucial factors to drive the temporal distribution of the soil bacterial
      community and diversity. In conclusion, the soil temperature, moisture and the
      nutrients N and P were the crucial edaphic factors for shaping the rhizospheric
      soil bacterial communities as season and climate change in a P. tabulaeformis
      forest of Qinling Mountains.

PMID- 30210465
TI  - Viability RT-qPCR to Distinguish Between HEV and HAV With Intact and Altered
      Capsids.
AB  - The hepatitis E virus (HEV) is an emerging pathogen showing a considerable
      increase in the number of reported cases in Europe mainly related to the
      ingestion of contaminated food. As with other relevant viral foodborne pathogens,
      real-time reverse transcriptase polymerase chain reaction (RT-qPCR) is the gold
      standard for HEV detection in clinical, food, and environmental samples, but
      these procedures cannot discriminate between inactivated and potentially
      infectious viruses. Thus, the aim of this study was to develop a viability PCR
      method to discriminate between native, heat-, and high-pressure processing (HPP)
      treated HEV using the hepatitis A virus (HAV) as a cultivable surrogate. To this
      end, different concentrations of viability markers (PMAxx and platinum chloride,
      PtCl4) were screened firstly on purified viral RNA using different RT-qPCR
      assays. Reductions of HEV RNA signals of >17.5, >15.0, and >15.5 quantification
      cycles (Cq) were reported for PtCl4 and 1.6, 2.9, and 8.4 Cq for PMAxx, clearly
      indicating a better performance of PtCl4 than PMAxx irrespective of the RT-qPCR
      assay used. The most efficient viability pretreatment (500 MUM PtCl4 incubated at
      5 degrees C for 30 min) was then assessed on native, heat-, and HPP-treated HEV
      suspension. The optimized viability RT-qPCR discriminated successfully between
      native, heat-, and HPP-treated HEV, to different extents depending on the
      experimental conditions. In particular, approximately 2-log10 reduction was
      reported by PtCl4-RT-qPCR at both 72 and 95 degrees C compared to the control.
      Additionally, both viability pretreatments were tested for HPP-treated HAV
      without success, while PtCl4-RT-qPCR completely eliminated (>5.6-log10 reduction)
      the RT-qPCR signals of HPP-treated HEV. Although this viability procedure may
      still overestimate infectivity, the PtCl4 pretreatment represents progress to
      better interpreting the quantification of intact HEV, and it could be included in
      molecular procedures used to quantify enteric viruses in food and environmental
      samples.

PMID- 30210464
TI  - Functional Characterization of c-di-GMP Signaling-Related Genes in the Probiotic
      Lactobacillus acidophilus.
AB  - The bacterial second messenger cyclic diguanylate monophosphate (c-di-GMP)
      regulates a series of cellular functions, including biofilm formation, motility,
      virulence, and other processes. In this study, we confirmed the presence of
      several c-di-GMP related genes and evaluated their activities and functions in
      Lactobacillus species. Bioinformatic and biochemical analyses revealed that
      Lactobacillus acidophilus La-14 have an active c-di-GMP phosphodiesterase (PdeA)
      that may act in the metabolic cycle of c-di-GMP. A GGDEF protein (DgcA) induced
      two c-di-GMP-dependent phenotypes (low motility and high production of curli
      fimbriae) in Escherichia coli by heterologously expressed in vivo but showed no
      diguanylate cyclases activity in vitro while in the expression without the N
      terminal transmembrane domain. The degenerated EAL-domain protein (PdeB), encoded
      by the last gene in the gts operon, serve as a c-di-GMP receptor which may be
      associated with exopolysaccharide (EPS) synthesis in L. acidophilus.
      Heterologously expressed GtsA and GtsB, encoded by the gts operon, stimulated EPS
      and biofilm formation in E. coli BL21. Constitutive expression in L. acidophilus
      revealed that a high concentration of intracellular DgcA levels increased EPS
      production in L. acidophilus and enhanced the co-aggregation ability with E. coli
      MG1655, which may be beneficial to the probiotic properties of Lactobacillus
      species. Our study imply that the c-di-GMP metabolism-related genes, in L.
      acidophilus, work jointly to regulate its functions in EPS formation and co
      aggregation.

PMID- 30210467
TI  - Effect of Pressure, Reconstituted RTE Meat Microbiota, and Antimicrobials on
      Survival and Post-pressure Growth of Listeria monocytogenes on Ham.
AB  - Pressure treatment of ready-to-eat (RTE) meats extends the shelf life and reduces
      risks associated with Listeria monocytogenes. However, pressure reduces numbers
      of Listeria on ham by less than 5 log (CFU/g) and pressure effects on other meat
      microbiota are poorly documented. This study investigated the impact of pressure
      and RTE meat microbiota, with or without nisin and rosemary oil, on survival of
      Listeria after refrigerated storage. Ham was inoculated with a 5-strain cocktail
      of L. monocytogenes alone or with a cocktail of RTE meat microbiota consisting of
      Brochothrix thermosphacta, Carnobacterium maltaromaticum, Leuconostoc gelidum,
      and Lactobacillussakei. Products were treated at 500 MPa at 5 degrees C for 1 or
      3 min, with or without rosemary extract or nisin. Surviving cells were
      differentially enumerated after pressure treatment and after 4 weeks of
      refrigerated storage. After 4 weeks of storage, products were also analyzed by
      high throughput sequencing of 16S rRNA amplicons. Pressure treatment reduced
      counts of Listeria by 1 to 2 log (CFU/g); inactivation of RTE meat microbiota was
      comparable. Counts of Listeria increased by 1-3 log (CFU/g) during refrigerated
      storage. RTE meat microbiota did not influence pressure inactivation of Listeria
      but prevented growth of Listeria during refrigerated storage. Rosemary extract
      did not influence bacterial inactivation or growth. The combination of nisin with
      pressure treatment for 3 min reduced counts of Listeria and meat microbiota by >5
      log (CFU/g); after 4 weeks of storage, counts were below the detection limit. In
      conclusion, pressure alone does not eliminate Listeria or other microbiota on RTE
      ham; however, the presence of non-pathogenic microbiota prevents growth of
      Listeria on pressure treated ham and has a decisive influence on post-pressure
      survival and growth.

PMID- 30210466
TI  - Global Transcriptomic Analysis and Function Identification of Malolactic Enzyme
      Pathway of Lactobacillus paracasei L9 in Response to Bile Stress.
AB  - Tolerance to bile stress is crucial for Lactobacillus paracasei to survive in the
      intestinal tract and exert beneficial actions. In this work, global
      transcriptomic analysis revealed that 104 genes were significantly changed
      (log2FoldChange > 1.5, P < 0.05) in detected transcripts of L. paracasei L9 when
      exposed to 0.13% Ox-bile. The different expressed genes involved in various
      biological processes, including carbon source utilization, amino acids and
      peptide metabolism processes, transmembrane transport, transcription factors, and
      membrane proteins. It is noteworthy that gene mleS encoding malolactic enzyme
      (MLE) was 2.60-fold up-regulated. Meanwhile, L-malic acid was proved to enhance
      bile tolerance, which could be attributed to the intracellular alkalinization
      caused by MLE pathway. In addition, membrane vesicles were observed under bile
      stress, suggesting a disturbance in membrane charge without L-malic acid. Then,
      genetic and physiological experiments revealed that MLE pathway enhanced the bile
      tolerance by maintaining a membrane balance in L. paracasei L9, which will
      provide new insight into the molecular basis of MLE pathway involved in bile
      stress response in Lactic acid bacteria.

PMID- 30210462
TI  - Emergent Properties of Microbial Activity in Heterogeneous Soil
      Microenvironments: Different Research Approaches Are Slowly Converging, Yet Major
      Challenges Remain.
AB  - Over the last 60 years, soil microbiologists have accumulated a wealth of
      experimental data showing that the bulk, macroscopic parameters (e.g.,
      granulometry, pH, soil organic matter, and biomass contents) commonly used to
      characterize soils provide insufficient information to describe quantitatively
      the activity of soil microorganisms and some of its outcomes, like the emission
      of greenhouse gasses. Clearly, new, more appropriate macroscopic parameters are
      needed, which reflect better the spatial heterogeneity of soils at the microscale
      (i.e., the pore scale) that is commensurate with the habitat of many
      microorganisms. For a long time, spectroscopic and microscopic tools were lacking
      to quantify processes at that scale, but major technological advances over the
      last 15 years have made suitable equipment available to researchers. In this
      context, the objective of the present article is to review progress achieved to
      date in the significant research program that has ensued. This program can be
      rationalized as a sequence of steps, namely the quantification and modeling of
      the physical-, (bio)chemical-, and microbiological properties of soils, the
      integration of these different perspectives into a unified theory, its upscaling
      to the macroscopic scale, and, eventually, the development of new approaches to
      measure macroscopic soil characteristics. At this stage, significant progress has
      been achieved on the physical front, and to a lesser extent on the (bio)chemical
      one as well, both in terms of experiments and modeling. With regard to the
      microbial aspects, although a lot of work has been devoted to the modeling of
      bacterial and fungal activity in soils at the pore scale, the appropriateness of
      model assumptions cannot be readily assessed because of the scarcity of relevant
      experimental data. For significant progress to be made, it is crucial to make
      sure that research on the microbial components of soil systems does not keep
      lagging behind the work on the physical and (bio)chemical characteristics.
      Concerning the subsequent steps in the program, very little integration of the
      various disciplinary perspectives has occurred so far, and, as a result,
      researchers have not yet been able to tackle the scaling up to the macroscopic
      level. Many challenges, some of them daunting, remain on the path ahead.
      Fortunately, a number of these challenges may be resolved by brand new measuring
      equipment that will become commercially available in the very near future.

PMID- 30210469
TI  - Lactic Acid Bacterium Population Dynamics in Artisan Sourdoughs Over One Year of
      Daily Propagations Is Mainly Driven by Flour Microbiota and Nutrients.
AB  - This study aimed to: (i) assess at what extent traditional, daily propagated,
      sourdough can be considered a stable microbial ecosystem; (ii) ascertain the
      drivers of stability/variability. For this purpose, samples of sourdough, flour
      and environment were collected over 1 year from three different bakeries located
      in Altamura, Castellana Grotte, and Matera. Culture-dependent and -independent
      analyses were carried out on all the samples. In addition, sourdough and flour
      were subjected to biochemical characterization. In all the sourdoughs sampled at
      the same bakery, cell density of lactic acid bacteria fluctuated of one-two log
      cycles. However, 16S metagenetic analysis showed that sourdough bacterial
      microbiota was remarkably stable, in terms of species. Yet, some differences were
      found during time at intra-specific level. Indeed, bacterial strains succeeded in
      a 1-year lapse of time or even in 6-months, such as in the case of strains
      isolated from Altamura sourdough samples. Residual carbohydrates, lactic acid,
      ethanol and free amino acids varied in the same sourdough collected at different
      sampling times. These variations could be attributed to combination of various
      factors, such as fermentation temperature and strain succession. In addition,
      concentration of flour nutrients varied over 1 year and, in some cases, in a
      shorter time lapse. This may have favored certain strains over others. For this
      reason and also because of its inherent contamination by lactic acid bacteria, we
      found flour as the major driver of strains succession.

PMID- 30210470
TI  - Intestinal Microbiome-Metabolome Responses to Essential Oils in Piglets.
AB  - This study investigated the effects of dietary essential oils (EOs) on intestinal
      microbial composition and metabolic profiles in weaned piglets. The piglets were
      fed the same basal diet supplemented with EOs (EO) or without EOs (Con) in the
      current study. The results showed that the body weight gain was significantly
      increased, while the diarrhea incidence was significantly reduced in the EO
      group. In addition, EOs could modify the intestinal microbial composition of
      weaned piglets. The relative abundances of some beneficial bacterial species such
      as Bacilli, Lactobacillales, Streptococcaceae, and Veillonellaceae were
      significantly increased in the EO group. Metabolomics analysis indicated that
      protein biosynthesis, amino acid metabolism, and lipid metabolism were enriched
      in the EO group. And correlation analysis demonstrated that some gut bacterial
      genera were highly correlated with altered gut microbiota-related metabolites.
      Taken together, this study indicated that dietary EOs not only altered microbial
      composition and function but modulated the microbial metabolic profiles in the
      colon, which might help us understand EOs' beneficial effects on intestinal
      health of weaned piglets.

PMID- 30210468
TI  - Genomic Insights Into the Acid Adaptation of Novel Methanotrophs Enriched From
      Acidic Forest Soils.
AB  - Soil acidification is accelerated by anthropogenic and agricultural activities,
      which could significantly affect global methane cycles. However, detailed
      knowledge of the genomic properties of methanotrophs adapted to acidic soils
      remains scarce. Using metagenomic approaches, we analyzed methane-utilizing
      communities enriched from acidic forest soils with pH 3 and 4, and recovered near
      complete genomes of proteobacterial methanotrophs. Novel methanotroph genomes
      designated KS32 and KS41, belonging to two representative clades of methanotrophs
      (Methylocystis of Alphaproteobacteria and Methylobacter of Gammaproteobacteria),
      were dominant. Comparative genomic analysis revealed diverse systems of membrane
      transporters for ensuring pH homeostasis and defense against toxic chemicals.
      Various potassium transporter systems, sodium/proton antiporters, and two copies
      of proton-translocating F1F0-type ATP synthase genes were identified, which might
      participate in the key pH homeostasis mechanisms in KS32. In addition, the V-type
      ATP synthase and urea assimilation genes might be used for pH homeostasis in
      KS41. Genes involved in the modification of membranes by incorporation of
      cyclopropane fatty acids and hopanoid lipids might be used for reducing proton
      influx into cells. The two methanotroph genomes possess genes for elaborate heavy
      metal efflux pumping systems, possibly owing to increased heavy metal toxicity in
      acidic conditions. Phylogenies of key genes involved in acid adaptation, methane
      oxidation, and antiviral defense in KS41 were incongruent with that of 16S rRNA.
      Thus, the detailed analysis of the genome sequences provides new insights into
      the ecology of methanotrophs responding to soil acidification.

PMID- 30210472
TI  - A Hydrophobic Small Protein, BpOF4_01690, Is Critical for Alkaliphily of
      Alkaliphilic Bacillus pseudofirmus OF4.
AB  - A monocistronic small protein, BpOF4_01690, was annotated in alkaliphilic
      Bacillus pseudofirmus OF4. It comprises 59 amino acids and is hydrophobic.
      Importantly, homologs of this protein were identified only in alkaliphiles. In
      this study, a mutant with a BpOF4_01690 gene deletion (designated Delta01690)
      exhibited weaker growth than that of the wild type in both malate-based defined
      and glucose-based defined media under low-sodium conditions at pH 10.5.
      Additionally, the enzymatic activity of the respiratory chain of Delta01690 was
      much lower than that of the wild type. These phenotypes were similar to those of
      a ctaD deletion mutant and an atpB-F deletion mutant. Therefore, we hypothesize
      that BpOF4_01690 plays a critical role in oxidative phosphorylation under highly
      alkaline conditions.

PMID- 30210473
TI  - Intra-host Symbiont Diversity and Extended Symbiont Maintenance in Photosymbiotic
      Acantharea (Clade F).
AB  - Photosymbiotic protists contribute to surface primary production in low-nutrient,
      open-ocean ecosystems and constitute model systems for studying plastid
      acquisition via endosymbiosis. Little is known, however, about host-symbiont
      dynamics in these important relationships, and whether these symbioses are
      mutualistic is debated. In this study, we applied single-cell sequencing methods
      and advanced fluorescent microscopy to investigate host-symbiont dynamics in
      clade F acantharians, a major group of photosymbiotic protists in oligotrophic
      subtropical gyres. We amplified the 18S rRNA gene from single acantharian hosts
      and environmental samples to assess intra-host symbiont diversity and to
      determine whether intra-host symbiont community composition directly reflects the
      available symbiont community in the surrounding environment. Our results
      demonstrate that clade F acantharians simultaneously host multiple species from
      the haptophyte genera Phaeocystis and Chrysochromulina. The intra-host symbiont
      community composition was distinct from the external free-living symbiont
      community, suggesting that these acantharians maintain symbionts for extended
      periods of time. After selectively staining digestive organelles, fluorescent
      confocal microscopy showed that symbionts were not being systematically digested,
      which is consistent with extended symbiont maintenance within hosts. Extended
      maintenance within hosts may benefit symbionts through protection from grazing or
      viral lysis, and therefore could enhance dispersal, provided that symbionts
      retain reproductive capacity. The evidence for extended symbiont maintenance
      therefore allows that Phaeocystis could glean some advantage from the symbiosis
      and leaves the possibility of mutualism.

PMID- 30210471
TI  - Genomic Description of 'Candidatus Abyssubacteria,' a Novel Subsurface Lineage
      Within the Candidate Phylum Hydrogenedentes.
AB  - The subsurface biosphere is a massive repository of fixed carbon, harboring
      approximately 90% of Earth's microbial biomass. These microbial communities drive
      transformations central to Earth's biogeochemical cycles. However, there is still
      much we do not understand about how complex subterranean microbial communities
      survive and how they interact with these cycles. Recent metagenomic investigation
      of deeply circulating terrestrial subsurface fluids revealed the presence of
      several novel lineages of bacteria. In one particular example, phylogenomic
      analyses do not converge on any one previously identified taxon; here we describe
      the first full genomic sequences of a new bacterial lineage within the candidate
      phylum Hydrogenedentes, 'Candidatus Abyssubacteria.' A global survey revealed
      that members of this proposed lineage are widely distributed in both marine and
      terrestrial subsurface environments, but their physiological and ecological roles
      have remained unexplored. Two high quality metagenome assembled genomes (SURF_5:
      97%, 4%; SURF_17: 91% and 4% completeness and contamination, respectively) were
      reconstructed from fluids collected 1.5 kilometers below surface in the former
      Homestake gold mine-now the Sanford Underground Research Facility (SURF)-in Lead,
      South Dakota, United States. Metabolic reconstruction suggests versatile
      metabolic capability, including possible nitrogen reduction, sulfite oxidation,
      sulfate reduction and homoacetogenesis. This first glimpse into the metabolic
      capabilities of these cosmopolitan bacteria suggests that they are involved in
      key geochemical processes, including sulfur, nitrogen, and carbon cycling, and
      that they are adapted to survival in the dark, often anoxic, subsurface
      biosphere.

PMID- 30210474
TI  - Insights Into Culturomics of the Rumen Microbiome.
AB  - Cultivation of undescribed rumen microorganisms is one of the most important
      tasks in rumen microbiology. In this study, we aimed to discover the potential of
      culturomics for characterizing the rumen microbiome and for identifying factors,
      specifically sample dilution and media type, which affect microbial richness on
      agar plates. Our cultivation experiment captured 23% of all operational taxonomic
      units (OTUs) found in the rumen microbiome in this study. The use of different
      media increased the number of cultured OTUs by up to 40%. Sample dilution had the
      strongest effect on increasing richness on the plates, while abundance and
      phylogeny were the main factors determining cultivability of rumen microbes. Our
      findings from phylogenetic analysis of cultured OTUs on the lower branches of the
      phylogenetic tree suggest that multifactorial traits govern cultivability.
      Interestingly, most of our cultured OTUs belonged to the rare rumen biosphere.
      These cultured OTUs could not be detected in the rumen microbiome, even when we
      surveyed it across a 38 rumen microbiome samples. These findings add another
      unique dimension to the complexity of the rumen microbiome and suggest that a
      large number of different organisms can be cultured in a single cultivation
      effort.

PMID- 30210475
TI  - The Microbiome of the Gastrointestinal Tract of a Range-Shifting Marine
      Herbivorous Fish.
AB  - Globally, marine species' distributions are being modified due to rising ocean
      temperatures. Increasing evidence suggests a circum-global pattern of poleward
      extensions in the distributions of many tropical herbivorous species, including
      the ecologically important rabbitfish Siganus fuscescens. Adaptability of a
      species to such new environments may be heavily influenced by the composition of
      their gastrointestinal microbe fauna, which is fundamentally important to animal
      health. Siganus fuscescens thus provides an opportunity to assess the stability
      of gastrointestinal microbes under varying environmental conditions. The
      gastrointestinal microbial communities of S. fuscescens were characterized over
      2,000 km of Australia's western coast, from tropical to temperate waters,
      including near its current southern distributional limit. Sequencing of the 16S
      rRNA gene demonstrated that each population had a distinct hindgut microbial
      community, and yet, 20 OTUs occurred consistently in all samples. These OTUs were
      considered the 'core microbiome' and were highly abundant, composing between 31
      and 54% of each population. Furthermore, levels of short chain fatty acids, an
      indicator of microbial fermentation activity, were similar among tropical and
      temperate locations. These data suggest that flexibility in the hindgut
      microbiome may play a role in enabling such herbivores to colonize new
      environments beyond their existing range.

PMID- 30210476
TI  - Phenotypic Diversity of Lactobacillus sakei Strains.
AB  - Lactobacillus sakei is a lactic acid bacteria (LAB) species highly adapted to the
      meat environment. For this reason, selected strains are often used as starter
      culture in the production of fermented sausages, especially in Mediterranean
      countries. It often represents the dominant species in these products and can
      maintain its viability during all the ripening period, which can take also some
      months. This ability is guaranteed by the possibility of the species to obtain
      energy through pathways active even when hexoses are depleted. This species is
      characterized by a relevant genetic and phenotypic diversity and its metabolism
      can be further affected by the growth condition applied. In this work we
      investigate the metabolic responses of six different L. sakei in a synthetic
      medium (DM) containing defined amounts of amino acids in relation to temperature
      and NaCl concentration. In addition, the activities of cells pre-grown in
      presence of glucose o ribose were tested. Arginine was efficiently up-taken with
      the exception of the type strain DSMZ 20017t. Other amino acids (i.e., serine,
      asparagine, cysteine, and methionine) were metabolized through potentially
      energetic pathways which start from pyruvate accumulation, as demonstrated by the
      organic acid accumulation trend in the condition tested, especially in DM without
      sugar added. The presence of excesses of pyruvate deriving from amino acids lead
      to the accumulation of diacetyl and acetoin by all the strains when sugars were
      added. This approach allowed a deeper insight into the phenotypic variability of
      the species and improved the comprehension of the metabolic pathways adopted by
      L. sakei to survive and grow in restrictive conditions such as those found in
      fermented sausages during fermentations. Thus, the results obtained are useful
      information for improving and optimizing the use of such strains as starter
      culture for these products.

PMID- 30210477
TI  - Probiotic Bacillus amyloliquefaciens C-1 Improves Growth Performance, Stimulates
      GH/IGF-1, and Regulates the Gut Microbiota of Growth-Retarded Beef Calves.
AB  - Growth retardation of calves is defined as a symptom of impaired growth and
      development, probably due to growth hormone disorder as well as natural and
      environmental factors in livestock. The growth-promoting effects of probiotics
      were determined in 50 growth-retarded growth calves. They were supplied with
      Bacillus amyloliquefaciens C-1 (Ba, 4 * 1010CFU/d, n = 16), B. subtilis (Bs, 4 *
      1010CFU/d, n = 18), and negative control (NC, n = 16) for 30 days. Pre- and post
      intervention, the growth performance (weight gain rate, feed intake and feed
      conversion rate) was analyzed, the serum GH, IGH-1 and immunoglobulin levels were
      assayed, and the fecal microbiota was detected. Calves in Ba and Bs groups
      demonstrated increased body weight gain, feed intake and GH/IGF-1 levels, as well
      as a more efficient feed conversion rate, compared with NC group (P < 0.05).
      Additionally, the abundances of bacteria contributing to the production of energy
      and SCFAs (short chain fatty acids), including Proteobacteria, Rhodospirillaceae,
      Campylobacterales, and Butyricimonas were increased compared with NC group (P <
      0.05, FDR < 0.1); and the suspected pathogens, which included Anaeroplasma and
      Acholeplasma were decreased (P < 0.05, FDR < 0.1) in both the Bs and Ba groups.
      Akkermansia, which is involved in the intestinal mucosal immune response, was
      increased in Bs group after intervention (P < 0.05, FDR < 0.1), but exhibited no
      obvious difference in Ba group. The increased bacterial genera in Ba group were
      Sphaerochaeta and Treponema (P < 0.05, FDR < 0.1). These results indicate that
      the probiotics B. amyloliquefaciens and B. subtilis exhibited similar therapeutic
      potential in terms of growth performance by regulating hormones, and improving
      the intestinal and rumen development in growth-retarded animals.

PMID- 30210479
TI  - Oral Microbiome Shifts From Caries-Free to Caries-Affected Status in 3-Year-Old
      Chinese Children: A Longitudinal Study.
AB  - As one of the most prevalent human infectious diseases, dental caries results
      from dysbiosis of the oral microbiota driven by multiple factors. However, most
      of caries studies were cross-sectional and mainly focused on the differences in
      the oral microbiota between caries-free (CF) and caries-affected (CA)
      populations, while little is known about the dynamic shift in microbial
      composition, and particularly the change in species association pattern during
      disease transition. Here, we reported a longitudinal study of a 12-month follow
      up of a cohort of 3-year-old children. Oral examinations and supragingival plaque
      collections were carried out at the beginning and every subsequent 6 months, for
      a total of three time points. All the children were CF at enrollment. Children
      who developed caries at 6-month follow-up but had not received any dental
      treatment until the end of the study were incorporated into the CA group.
      Children who remained CF at the end of the study were incorporated into the CF
      group. Using Illumina Miseq Sequencing of the 16S rRNA gene, we monitored the
      shift of supragingival microbiome during caries initiation and progression in
      children who developed caries over the 12-month study period. Intriguingly,
      principle coordinates analyses revealed two major shifting patterns in microbial
      structures during caries initiation and progression in CA group, but not in CF
      group. Dynamic co-occurring OTU network study showed that compared to CF group,
      there was significant increase in both number and intensity of correlations
      between microbial taxa, as well as the formation of tight clusters of specific
      bacteria in CA group. Furthermore, there were enhanced correlations, positive
      ones between CA-enriched taxa, and negative ones between CF-enriched and CA
      enriched species within CA group. Our data suggested coordinated microbial
      interactions could be essential to caries pathogenesis. Most importantly, our
      study indicated that significant microbial shifts occur not only during caries
      development, but even in the sub-clinical state. Using supragingival microbiome
      profiles, we were able to construct a caries-onset prediction model with a
      prediction accuracy of 93.1%. Our study indicated that the microbial shifts prior
      to the onset of caries might potentially be used for the early diagnosis and
      prediction of caries.

PMID- 30210478
TI  - A General Protein O-Glycosylation Gene Cluster Encodes the Species-Specific
      Glycan of the Oral Pathogen Tannerella forsythia: O-Glycan Biosynthesis and
      Immunological Implications.
AB  - The cell surface of the oral pathogen Tannerella forsythia is heavily
      glycosylated with a unique, complex decasaccharide that is O-glycosidically
      linked to the bacterium's abundant surface (S-) layer, as well as other proteins.
      The S-layer glycoproteins are virulence factors of T. forsythia and there is
      evidence that protein O-glycosylation underpins the bacterium's pathogenicity. To
      elucidate the protein O-glycosylation pathway, genes suspected of encoding
      pathway components were first identified in the genome sequence of the ATCC 43037
      type strain, revealing a 27-kb gene cluster that was shown to be polycistronic.
      Using a gene deletion approach targeted at predicted glycosyltransferases (Gtfs)
      and methyltransferases encoded in this gene cluster, in combination with mass
      spectrometry of the protein-released O-glycans, we show that the gene cluster
      encodes the species-specific part of the T. forsythia ATCC 43037 decasaccharide
      and that this is assembled step-wise on a pentasaccharide core. The core was
      previously proposed to be conserved within the Bacteroidetes phylum, to which T.
      forsythia is affiliated, and its biosynthesis is encoded elsewhere on the
      bacterial genome. Next, to assess the prevalence of protein O-glycosylation among
      Tannerella sp., the publicly available genome sequences of six T. forsythia
      strains were compared, revealing gene clusters of similar size and organization
      as found in the ATCC 43037 type strain. The corresponding region in the genome of
      a periodontal health-associated Tannerella isolate showed a different gene
      composition lacking most of the genes commonly found in the pathogenic strains.
      Finally, we investigated whether differential cell surface glycosylation impacts
      T. forsythia's overall immunogenicity. Release of proinflammatory cytokines by
      dendritic cells (DCs) upon stimulation with defined Gtf-deficient mutants of the
      type strain was measured and their T cell-priming potential post-stimulation was
      explored. This revealed that the O-glycan is pivotal to modulating DC effector
      functions, with the T. forsythia-specific glycan portion suppressing and the
      pentasaccharide core activating a Th17 response. We conclude that complex protein
      O-glycosylation is a hallmark of pathogenic T. forsythia strains and propose it
      as a valuable target for the design of novel antimicrobials against
      periodontitis.

PMID- 30210480
TI  - Yeast Probiotics Shape the Gut Microbiome and Improve the Health of Early-Weaned
      Piglets.
AB  - Weaning is one of the most stressful challenges in the pig's life, which
      contributes to dysfunctions of intestinal and immune system, disrupts the gut
      microbial ecosystem, and therefore compromises the growth performance and health
      of piglets. To mitigate the negative impact of the stress on early-weaned
      piglets, effective measures are needed to promote gut health. Toward this end, we
      tamed a Saccharomyces cerevisiae strain and developed a probiotic Duan-Nai-An,
      which is a yeast culture of the tamed S. cerevisiae on egg white. In this study,
      we tested the performance of Duan-Nai-An on growth and health of early-weaned
      piglets and analyzed its impact on fecal microbiota. The results showed that Duan
      Nai-An significantly improved weight gain and feed intake, and reduced diarrhea
      and death of early-weaned piglets. Analysis of the gut microbiota showed that the
      bacterial community was shaped by Duan-Nai-An and maintained as a relatively
      stable structure, represented by a higher core OTU number and lower unweighted
      UniFrac distances across the early weaned period. However, fungal community was
      not significantly shaped by the yeast probiotics. Notably, 13 bacterial genera
      were found to be associated with Duan-Nai-An feeding, including Enterococcus,
      Succinivibrio, Ruminococcus, Sharpea, Desulfovibrio, RFN20, Sphaerochaeta,
      Peptococcus, Anaeroplasma, and four other undefined genera. These findings
      suggest that Duan-Nai-An has the potential to be used as a feed supplement in
      swine production.

PMID- 30210481
TI  - Genome Sequencing Reveals a Large and Diverse Repertoire of Antimicrobial
      Peptides.
AB  - Competition among bacterial members of the same ecological niche is mediated by
      bacteriocins: antimicrobial peptides produced by bacterial species to kill other
      bacteria. Bacteriocins are also promising candidates for novel antimicrobials.
      Streptococcus pneumoniae (the "pneumococcus") is a leading cause of morbidity and
      mortality worldwide and a frequent colonizer of the human nasopharynx. Here, 14
      newly discovered bacteriocin gene clusters were identified among >6,200
      pneumococcal genomes. The molecular epidemiology of the bacteriocin clusters was
      investigated using a large global and historical pneumococcal dataset dating from
      1916. These analyses revealed extraordinary bacteriocin diversity among
      pneumococci and the majority of bacteriocin clusters were also found in other
      streptococcal species. Genomic hotspots for the integration of different
      bacteriocin gene clusters were discovered. Experimentally, bacteriocin genes were
      transcriptionally active when the pneumococcus was under stress and when two
      strains were co-cultured in broth. These findings reveal much more diversity
      among bacterial defense mechanisms than previously appreciated, which
      fundamentally broaden our understanding of bacteriocins relative to intraspecies
      and interspecies nasopharyngeal competition and bacterial population structure.

PMID- 30210482
TI  - Iron Deficiency Generates Oxidative Stress and Activation of the SOS Response in
      Caulobacter crescentus.
AB  - In C. crescentus, iron metabolism is mainly controlled by the transcription
      factor Fur (ferric uptake regulator). Iron-bound Fur represses genes related to
      iron uptake and can directly activate the expression of genes for iron-containing
      proteins. In this work, we used total RNA sequencing (RNA-seq) of wild type C.
      crescentus growing in minimal medium under iron limitation and a fur mutant
      strain to expand the known Fur regulon, and to identify novel iron-regulated
      genes. The RNA-seq of cultures treated with the iron chelator 2-2-dypiridyl (DP)
      allowed identifying 256 upregulated genes and 236 downregulated genes, being 176
      and 204 newly identified, respectively. Sixteen transcription factors and seven
      sRNAs were upregulated in iron limitation, suggesting that the response to low
      iron triggers a complex regulatory network. Notably, lexA along with most of its
      target genes were upregulated, suggesting that DP treatment caused DNA damage,
      and the SOS DNA repair response was activated in a RecA-dependent manner, as
      confirmed by RT-qPCR. Fluorescence microscopy assays using an oxidation-sensitive
      dye showed that wild type cells in iron limitation and the fur mutant were under
      endogenous oxidative stress, and a direct measurement of cellular H2O2 showed
      that cells in iron-limited media present a higher amount of endogenous H2O2. A
      mutagenesis assay using the rpoB gene as a reporter showed that iron limitation
      led to an increase in the mutagenesis rate. These results showed that iron
      deficiency causes C. crescentus cells to suffer oxidative stress and to activate
      the SOS response, indicating an increase in DNA damage.

PMID- 30210484
TI  - Complete Genome of the Xanthomonas euvesicatoria Specific Bacteriophage KPhi1,
      Its Survival and Potential in Control of Pepper Bacterial Spot.
AB  - Xanthomonas euvesicatoria phage KPhi1, a member of Myoviridae family, was
      isolated from the rhizosphere of pepper plants showing symptoms of bacterial
      spot. The phage strain expressed antibacterial activity to all X. euvesicatoria
      strains tested and did not lyse other Xanthomonas spp., nor other less related
      bacterial species. The genome of KPhi1 is double-stranded DNA of 46.077 bp
      including 66 open reading frames and an average GC content of 62.9%, representing
      the first complete genome sequence published for a phage infecting xanthomonads
      associated with pepper or tomato. The highest genome similarity was observed
      between phage KPhi1 and the Xanthomonas oryzae pv. oryzae specific phage OP2. On
      the other hand, when compared with other members of the genus Bcep78virus, the
      genome similarity was lower. Forty-four (67%) predicted KPhi1 proteins shared
      homology with Xanthomonas phage OP2, while 20 genes (30%) were unique to KPhi1.
      Phage KPhi1, which is chloroform resistant and stable in different media and in
      the pH range 5-11, showed a high titer storage ability for at least 2 years at +4
      degrees C. Copper-hydroxide and copper-oxychloride reduced phage activity
      proportionally to the used concentrations and the exposure time. UV light was
      detrimental to the phage strain, but skim milk plus sucrose formulation extended
      its survival in vitro. The phages survived for at least 7 days on the surface of
      pepper leaves in the greenhouse, showing the ability to persist on the plant
      tissue without the presence of the host bacterium. Results of three repeated
      experiments showed that foliar applications of the unformulated KPhi1 phage
      suspension effectively controlled pepper bacterial spot compared to the standard
      treatment and the untreated control. The integration of the phage KPhi1 and
      copper-hydroxide treatments resulted in an increased efficacy compared to the
      copper-hydroxide alone.

PMID- 30210483
TI  - Impact of Chromosomal Architecture on the Function and Evolution of Bacterial
      Genomes.
AB  - The bacterial nucleoid is highly condensed and forms compartment-like structures
      within the cell. Much attention has been devoted to investigating the dynamic
      topology and organization of the nucleoid. In contrast, the specific nucleoid
      organization, and the relationship between nucleoid structure and function is
      often neglected with regard to importance for adaption to changing environments
      and horizontal gene acquisition. In this review, we focus on the structure
      function relationship in the bacterial nucleoid. We provide an overview of the
      fundamental properties that shape the chromosome as a structured yet dynamic
      macromolecule. These fundamental properties are then considered in the context of
      the living cell, with focus on how the informational flow affects the nucleoid
      structure, which in turn impacts on the genetic output. Subsequently, the dynamic
      living nucleoid will be discussed in the context of evolution. We will address
      how the acquisition of foreign DNA impacts nucleoid structure, and conversely,
      how nucleoid structure constrains the successful and sustainable chromosomal
      integration of novel DNA. Finally, we will discuss current challenges and
      directions of research in understanding the role of chromosomal architecture in
      bacterial survival and adaptation.

PMID- 30210485
TI  - Vertical Distribution of Microbial Eukaryotes From Surface to the Hadal Zone of
      the Mariana Trench.
AB  - Marine microbial eukaryotes are ubiquitous, comprised of phylogenetically diverse
      groups and play key roles in microbial food webs and global biogeochemical
      cycling. However, their vertical distribution in the deep sea has received little
      attention. In this study, we investigated the composition and diversity of the
      eukaryotes of both 0.2-3 MUm and >3 MUm size fractions from the surface to the
      hadal zone (8727 m) of the Mariana Trench using Illumina MiSeq sequencing for the
      18S rDNA. The microbial eukaryotic community structure differed substantially
      across size fractions and depths. Operational taxonomic unit (OTU) richness in
      the >3 MUm fraction was higher than that in the 0.2-3 MUm fraction at the same
      depth. For the 0.2-3 MUm fraction, sequences of Retaria (Rhizaria) were most
      abundant in the surface water (53.5%). Chrysophyceae (Stramenopiles) sequences
      dominated mostly in the samples from water depths below 1795 m. For the >3 MUm
      fraction, sequences of Dinophyceae (Alveolata) were most abundant in surface
      waters (49.3%) and remained a significant proportion of total sequences at
      greater depths (9.8%, on average). Retaria sequences were abundant in samples of
      depths >=1000 m. Amoebozoa and Apusozoa sequences were enriched in the hadal
      sample, comprising 38 and 20.4% of total sequences, respectively. Fungi
      (Opisthokonta) sequences were most abundant at 1759 m in both size fractions.
      Strong positive associations were found between Syndiniales (mainly MALV-I and
      MALV-II) and Retaria while negative associations were shown between MALV-II and
      Fungi in a co-occurrence analysis. This study compared the community structure of
      microbial eukaryotes in different zones in the deep sea and identified a distinct
      hadal community in the larger size fraction, suggesting the uniqueness of the
      eukaryotes in the biosphere in the Mariana Trench.

PMID- 30210486
TI  - Inactivation of Foodborne Bacteria Biofilms by Aqueous and Gaseous Ozone.
AB  - In this study, the efficacy of treatments with ozone in water and gaseous ozone
      against attached cells and microbial biofilms of three foodborne species,
      Pseudomonas fluorescens, Staphylococcus aureus, and Listeria monocytogenes, was
      investigated. Biofilms formed on AISI 304 stainless steel coupons from a mixture
      of three strains (one reference and two wild strains) of each microbial species
      were subjected to three types of treatment for increasing times: (i) ozonized
      water (0.5 ppm) by immersion in static condition, (ii) ozonized water under flow
      conditions, and (iii) gaseous ozone at different concentrations (0.1-20 ppm). The
      Excel add-in GinaFit tool allowed to estimate the survival curves of attached
      cells and microbial biofilms, highlighting that, regardless of the treatment, the
      antimicrobial effect occurred in the first minutes of treatment, while by
      increasing contact times probably the residual biofilm population acquired
      greater resistance to ozonation. Treatment with aqueous ozone under static
      conditions resulted in an estimated viability reduction of 1.61-2.14 Log CFU/cm2
      after 20 min, while reduction values were higher (3.26-5.23 Log CFU/cm2) for
      biofilms treated in dynamic conditions. S. aureus was the most sensitive species
      to aqueous ozone under dynamic conditions. With regard to the use of gaseous
      ozone, at low concentrations (up to 0.2 ppm), estimated inactivations of 2.01
      2.46 Log CFU/cm2 were obtained after 60 min, while at the highest concentrations
      a complete inactivation (<10 CFU/cm2) of the biofilms of L. monocytogenes and the
      reduction of 5.51 and 4.72 Log CFU/cm2 of P. fluorescens and S. aureus
      respectively after 60 and 20 min were achieved. Considering the results, ozone in
      water form might be used in daily sanitation protocols at the end of the day or
      during process downtime, while gaseous ozone might be used for the treatment of
      confined spaces for longer times (e.g., overnight) and in the absence of
      personnel, to allow an eco-friendly control of microbial biofilms and
      consequently reduce the risk of cross-contamination in the food industry.

PMID- 30210487
TI  - Clinical Performance Evaluation of VersaTrek 528 Blood Culture System in a
      Chinese Tertiary Hospital.
AB  - Background: The aim of this study was to evaluate the clinical performance of
      VersaTrek 528 compared to BACTEC FX 400 blood culture (BC) systems. Materials and
      Methods: Simulated and clinically obtained BCs were used in the study. Confirmed
      bacterial species (n = 78), including 43 Gram-positives, 30 Gram-negatives, and 5
      Candida albicans strains, were each inoculated into BC bottles. Clinically
      obtained BCs were subdivided into two groups, A and B. In group A were 72 BC sets
      (pair: aerobic and anaerobic) in which a set inoculated with 5 ml blood was
      processed in the VersaTrek BC system, whilst the one inoculated with 10 ml blood
      was processed in the FX BC system. In group B, 76 BC sets (pairs) corresponding
      to 152 VersaTrek bottles and 152 FX bottles were inoculated with the same volume
      (10 ml) of blood, and processed in each system. Results: In the simulated BC
      study, 90% (63/70) of the VersaTrek aerobic bottles were positive, which was
      higher than that of FX 400 (59/70, 84%), but was not statistically significant (P
      = 0.423). In contrast, FX 400 anaerobic bottles had a higher positive rate than
      the other BC system (84 vs. 77%), although it was statistically insignificant (P
      = 0.267). Time to detection of organisms in the two BCs was comparable for both
      aerobic (P = 0.131) and anaerobic bottles (P = 0.104). In clinical BCs of group
      A, FX BC system had slightly higher positive rates for both aerobic (11.1 vs.
      9.7%, P = 0.312) and anaerobic (8.3 vs. 6.9%, P = 0.375) bottles. However, the
      difference was not statistically significant. In group B, VersaTrek aerobic
      bottles had a higher positive rate compared to the other BC system (10.5 vs.
      5.2%, P = 0.063). In terms of positive rates of sub-studies A and B, VersaTrek
      and FX BC systems were comparable. Conclusion: There was no significant
      difference between the two BC systems in the detection of bacteria and fungi in
      simulated BCs. In clinical BCs, the performance of the VersaTrek BC system, with
      inoculation of 5 or 10 ml patient's blood, was comparable to the FX system with
      inoculation of 10 ml patient's blood.

PMID- 30210488
TI  - Congenital Zika Virus Infection in Immunocompetent Mice Causes Postnatal Growth
      Impediment and Neurobehavioral Deficits.
AB  - A small percentage of babies born to Zika virus (ZIKV)-infected mothers manifest
      severe defects at birth, including microcephaly. Among those who appeared healthy
      at birth, there are increasing reports of postnatal growth or developmental
      defects. However, the impact of congenital ZIKV infection in postnatal
      development is poorly understood. Here, we report that a mild congenital ZIKV
      infection in pups born to immunocompetent pregnant mice did not display apparent
      defects at birth, but manifested postnatal growth impediments and neurobehavioral
      deficits, which include reduced locomotor and cognitive deficits that persisted
      into adulthood. We found that the brains of these pups were smaller, had a
      thinner cortical layer 1, displayed increased astrogliosis, decreased expression
      of microcephaly- and neuron development- related genes, and increased pathology
      as compared to mock-infected controls. In summary, our results showed that even a
      mild congenital ZIKV infection in immunocompetent mice could lead to postnatal
      deficits, providing definitive experimental evidence for a necessity to closely
      monitor postnatal growth and development of presumably healthy human infants,
      whose mothers were exposed to ZIKV infection during pregnancy.

PMID- 30210489
TI  - Physiological Response of Corynebacterium glutamicum to Increasingly Nutrient
      Rich Growth Conditions.
AB  - To ensure economic competitiveness, bioprocesses should achieve maximum
      productivities enabled by high growth rates (MU) and equally high substrate
      consumption rates (qS) as a prerequisite of sufficient carbon-to-product
      conversion. Both traits were investigated and improved via bioprocess engineering
      approaches studying the industrial work horse Corynebacterium glutamicum.
      Standard minimal medium CGXII with glucose as sole carbon source was supplemented
      with complex brain-heart-infusion (BHI) or amino acid (AA) cocktails. Maximum MU
      of 0.67 h-1 was exclusively observed in 37 g BHI L-1 whereas only minor growth
      stimulation was found after AA supplementation (MU = 0.468 h-1). Increasing
      glucose consumption rates (qGlc) were solely observed in certain dosages of BHI
      (1-10 g L-1), while 37 g BHI L-1 and AA addition revealed qGlc below the
      reference experiments. Moreover, BHI supplementation revealed Monod-type
      saturation kinetics of MU (KBHI = 2.73 g BHI L-1) referring to the preference of
      non-AAs as key boosting nutrients. ATP-demands under reference, 1 g BHI L-1, and
      AA conditions were nearly constant but halved in BHI concentrations above 5 g L-1
      reflecting the energetic advantage of consuming complex nutrient components in
      addition to "simple" building blocks such as AAs. Furthermore, C. glutamicum
      revealed maximum biomass per carbon yields of about 18 gCDW C-mol-1 irrespective
      of the medium. In AA supplementation experiments, simultaneous uptake of 17 AAs
      was observed, maximum individual consumption rates determined, and L-asparagine
      and L-glutamine were distinguished as compounds with the highest consumption
      rates. Employment of the expanded stoichiometric model iMG481 successfully
      reproduced experimental results and revealed the importance of C. glutamicum's
      transaminase network to compensate needs of limiting AA supply. Model-based
      sensitivity studies attributed the highest impact on MU to AAs with high ATP and
      NADPH demands such as L-tryptophan or L-phenylalanine.

PMID- 30210491
TI  - GM-CSF Quantity Has a Selective Effect on Granulocytic vs. Monocytic Myeloid
      Development and Function.
AB  - GM-CSF promotes myeloid differentiation of cultured bone marrow cells into cells
      of the granulocytic and monocytic lineage; the latter can further differentiate
      into monocytes/macrophages and dendritic cells. How GM-CSF selects for these
      different myeloid fates is unresolved. GM-CSF levels can change either
      iatrogenically (e.g., augmenting leukopoiesis after radiotherapy) or naturally
      (e.g., during infection or inflammation) resulting in different immunological
      outcomes. Therefore, we asked whether the dose of GM-CSF may regulate the
      development of three types of myeloid cells. Here, we showed that GM-CSF acted as
      a molecular rheostat where the quantity determined which cell type was favored;
      moreover, the cellular process by which this was achieved was different for each
      cell type. Thus, low quantities of GM-CSF promoted the granulocytic lineage,
      mainly through survival. High quantities promoted the monocytic lineage, mainly
      through proliferation, whereas moderate quantities promoted moDCs, mainly through
      differentiation. Finally, we demonstrated that monocytes/macrophages generated
      with different doses of GM-CSF differed in function. We contend that this
      selective effect of GM-CSF dose on myeloid differentiation and function should be
      taken into consideration during pathophysiological states that may alter GM-CSF
      levels and during GM-CSF agonistic or antagonistic therapy.

PMID- 30210490
TI  - Unimpaired Responses to Vaccination With Protein Antigen Plus Adjuvant in Mice
      With Kit-Independent Mast Cell Deficiency.
AB  - Innate inflammatory responses are crucial for induction and regulation of T cell
      and antibody responses. Mast cell (MC)-deficient Kit mutant mice showed impaired
      adaptive immunity, suggesting that MCs provide essential adjuvant activities, and
      pharmacological MC activation was proposed as a new adjuvant principle. However,
      the Kit mutations result in complex alterations of the immune system in addition
      to MC deficiency. We revisited the role of MCs in vaccination responses using
      Mcpt5-Cre R26DTA/DTA and Cpa3Cre/+ mice that lack connective tissue MCs or all
      MCs, respectively, but feature an otherwise normal immune system. These animals
      showed no impairment of T and B cell responses to intradermal vaccination with
      protein antigen plus complete Freund's adjuvant. Moreover, we demonstrate that
      the adjuvant effects of the MC secretagogue c48/80 in intradermal or mucosal
      immunization are independent of the presence of MCs. We hence find no evidence
      for a regulation by MCs of adaptive immune responses to protein antigens. The
      finding that immunological MC functions differ from those suggested by
      experiments in Kit mutants, emphasizes the importance of rigorous tests in Kit
      independent MC-deficiency models.

PMID- 30210492
TI  - Sex Hormones Determine Immune Response.

PMID- 30210493
TI  - The Role of CXCR3 and Associated Chemokines in the Development of Atherosclerosis
      and During Myocardial Infarction.
AB  - The chemokine receptor CXCR3 and associated CXC chemokines have been extensively
      investigated in several inflammatory and autoimmune diseases as well as in tumor
      development. Recent studies have indicated the role of these chemokines also in
      cardiovascular diseases. We aimed to present current knowledge regarding the role
      of CXCR3-binding chemokines in the pathogenesis of atherosclerosis and during
      acute myocardial infarction.

PMID- 30210495
TI  - BLTR1 in Monocytes Emerges as a Therapeutic Target For Vascular Inflammation With
      a Subsequent Intimal Hyperplasia in a Murine Wire-Injured Femoral Artery.
AB  - Given the importance of high-mobility group box 1 (HMGB1) and 5-lipoxygenase (5
      LO) signaling in vascular inflammation, we investigated the role of leukotriene
      signaling in monocytes on monocyte-to-macrophage differentiation (MMD) induced by
      HMGB1, and on vascular inflammation and subsequent intimal hyperplasia in a mouse
      model of wire-injured femoral artery. In cultured primary bone marrow-derived
      cells (BMDCs) stimulated with HMGB1, the number of cells with macrophage-like
      morphology was markedly increased in association with an increased expression of
      CD11b/Mac-1, which were attenuated in cells pre-treated with Zileuton, a 5-LO
      inhibitor as well as in 5-LO-deficient BMDCs. Of various leukotriene receptor
      inhibitors examined, which included leukotriene B4 receptors (BLTRs) and
      cysteinyl leukotriene receptors (cysLTRs), the BLTR1 inhibitor (U75302)
      exclusively suppressed MMD induction by HMGB1. The importance of BLTR1 in HMGB1
      induced MMD was also observed in BMDCs isolated from BLTR1-deficient mice and
      BMDCs transfected with BLTR1 siRNA. Although leukotriene B4 (LTB4) had minimal
      direct effects on MMD in control and 5-LO-deficient BMDCs, MMD attenuation by
      HMGB1 in 5-LO-deficient BMDCs was significantly reversed by exogenous LTB4, but
      not in BLTR1-deficient BMDCs, suggesting that LTB4/BLTR1-mediated priming of
      monocytes is a prerequisite of HMGB1-induced MMD. In vivo, both macrophage
      infiltration and intimal hyperplasia in our wire-injured femoral artery were
      markedly attenuated in BLTR1-deficient mice as compared with wild-type controls,
      but these effects were reversed in BLTR1-deficient mice transplanted with
      monocytes from control mice. These results suggest that BLTR1 in monocytes is a
      pivotal player in MMD with subsequent macrophage infiltration into neointima,
      leading to vascular remodeling after vascular injury.

PMID- 30210494
TI  - IgG-Independent Co-aggregation of FcepsilonRI and FcgammaRIIB Results in LYN- and
      SHIP1-Dependent Tyrosine Phosphorylation of FcgammaRIIB in Murine Bone Marrow
      Derived Mast Cells.
AB  - Activation of the high-affinity receptor for IgE (FcepsilonRI) follows a bell
      shaped dose-response curve. Upon supra-optimal stimulation, mast cell effector
      responses are down-regulated by inhibitory molecules like the SH2-containing
      inositol-5'-phosphatase SHIP1 and the SRC-family-kinase LYN. To identify further
      molecules involved in a negative regulatory signalosome, we screened for proteins
      showing the same pattern of tyrosine phosphorylation as SHIP1, which is tyrosine
      phosphorylated strongest upon supra-optimal antigen (Ag) stimulation. The low
      affinity IgG receptor, FcgammaRIIB, was found to be most strongly phosphorylated
      under supra-optimal conditions. This phosphorylation is the consequence of
      passive, Ag/IgE-dependent and progressive co-localization of FcepsilonRI and
      FcgammaRIIB, which is not dependent on IgG. Upon supra-optimal FcepsilonRI cross
      linking, FcgammaRIIB phosphorylation is executed by LYN and protected from
      dephosphorylation by SHIP1. Analysis of FcgammaRIIB-deficient bone marrow-derived
      mast cells revealed an ambiguous phenotype upon FcepsilonRI cross-linking.
      Absence of FcgammaRIIB significantly diminished the level of SHIP1
      phosphorylation and resulted in augmented Ca2+ mobilization. Though,
      degranulation and IL-6 production were only weakly altered. Altogether our data
      establish the LYN/FcgammaRIIB/SHIP1 signalosome in the context of FcepsilonRI
      activation, particularly at supra-optimal Ag concentrations. The fact that SHIP1
      tyrosine phosphorylation/activation not only depends on FcgammaRIIB, highlights
      the necessity for its tight backup control.

PMID- 30210498
TI  - Chimeric Proteins Containing MAP-1 and Functional Domains of C4b-Binding Protein
      Reveal Strong Complement Inhibitory Capacities.
AB  - The complement system is a tightly regulated network of proteins involved in
      defense against pathogens, inflammatory processes, and coordination of the innate
      and adaptive immune responses. Dysregulation of the complement cascade is
      associated with many inflammatory disorders. Thus, inhibition of the complement
      system has emerged as an option for treatment of a range of different
      inflammatory diseases. MAP-1 is a pattern recognition molecule (PRM)-associated
      inhibitor of the lectin pathway of the complement system, whereas C4b-binding
      protein (C4BP) regulates both the classical and lectin pathways. In this study we
      generated chimeric proteins consisting of MAP-1 and the first five domains of
      human C4BP (C4BP1-5) in order to develop a targeted inhibitor acting at different
      levels of the complement cascade. Two different constructs were designed and
      expressed in CHO cells where MAP-1 was fused with C4BP1-5 in either the C- or N
      terminus. The functionality of the chimeric proteins was assessed using different
      in vitro complement activation assays. Both chimeric proteins displayed the
      characteristic Ca2+-dependent dimerization and binding to PRMs of native MAP-1,
      as well as the co-factor activity of native C4BP. In ELISA-based complement
      activation assays they could effectively inhibit the lectin and classical
      pathways. Notably, MAP-1:C4BP1-5 was five times more effective than rMAP-1 and
      rC4BP1-5 applied at the same time, emphasizing the advantage of a single
      inhibitor containing both functional domains. The MAP-1/C4BP chimeras exert
      unique complement inhibitory properties and represent a novel therapeutic
      approach targeting both upstream and central complement activation.

PMID- 30210496
TI  - T Cell/B Cell Collaboration and Autoimmunity: An Intimate Relationship.
AB  - Co-ordinated interaction between distinct cell types is a hallmark of successful
      immune function. A striking example of this is the carefully orchestrated
      cooperation between helper T cells and B cells that occurs during the initiation
      and fine-tuning of T-cell dependent antibody responses. While these processes
      have evolved to permit rapid immune defense against infection, it is becoming
      increasingly clear that such interactions can also underpin the development of
      autoimmunity. Here we discuss a selection of cellular and molecular pathways that
      mediate T cell/B cell collaboration and highlight how in vivo models and genome
      wide association studies link them with autoimmune disease. In particular, we
      emphasize how CTLA-4-mediated regulation of CD28 signaling controls the
      engagement of secondary costimulatory pathways such as ICOS and OX40, and
      profoundly influences the capacity of T cells to provide B cell help. While our
      molecular understanding of the co-operation between T cells and B cells derives
      from analysis of secondary lymphoid tissues, emerging evidence suggests that
      subtly different rules may govern the interaction of T and B cells at ectopic
      sites during autoimmune inflammation. Accordingly, the phenotype of the T cells
      providing help at these sites includes notable distinctions, despite sharing core
      features with T cells imparting help in secondary lymphoid tissues. Finally, we
      highlight the interdependence of T cell and B cell responses and suggest that a
      significant beneficial impact of B cell depletion in autoimmune settings may be
      its detrimental effect on T cells engaged in molecular conversation with B cells.

PMID- 30210497
TI  - Role of CD1d- and MR1-Restricted T Cells in Asthma.
AB  - Innate T lymphocytes are a group of relatively recently identified T cells that
      are not involved in either innate or adaptive immunity. Unlike conventional T
      cells, most innate T lymphocytes express invariant T cell receptor to recognize
      exogenous non-peptide antigens presented by a family of non-polymorphic MHC class
      I-related molecules, such as CD1d and MHC-related molecule-1 (MR1). Invariant
      natural killer T (iNKT) cells and mucosal-associated invariant T (MAIT) cells
      quickly respond to the antigens bound to CD1d and MR1 molecules, respectively,
      and immediately exert effector functions by secreting various cytokines and
      granules. This review describes the detrimental and beneficial roles of iNKT
      cells in animal models of asthma and in human asthmatic patients and also
      addresses the mechanisms through which iNKT cells are activated by environmental
      or extracellular factors. We also discuss the potential for therapeutic
      interventions of asthma by specific antibodies against NKT cells. Furthermore, we
      summarize the recent reports on the role of MAIT cells in allergic diseases.

PMID- 30210499
TI  - The Cytotoxic Activity of Natural Killer Cells Is Suppressed by IL-10+ Regulatory
      T Cells During Acute Retroviral Infection.
AB  - Natural killer (NK) cells play a key role in host defense against cancer and
      viral infections. It was shown that NK cells are important for the control of
      acute retroviral infections, but their antiviral activity depends on multiple
      parameters such as viral inoculation dose, interactions with myeloid cell types
      and the cytokine milieu. In addition, during an ongoing retroviral infection
      regulatory T cells (Tregs) can suppress NK cell functions. However, the precise
      role of Tregs on the initial NK cell response and their immediate antiviral
      activity after an acute retroviral infection is still unknown. Here we show that
      thymus-derived Tregs suppress the proliferation, effector functions and
      cytotoxicity of NK cells very early during acute Friend Retrovirus (FV)
      infection. Tregs exhibited an activated phenotype and increased the production of
      the immunosuppressive cytokines IL-10 and TGF-beta after FV infection of mice.
      Neutralization of the immunosuppressive cytokine IL-10 resulted in a significant
      augmentation of NK cell functions. Although the activation of dendritic cells
      (DCs) and macrophages as well as the IL-15 cytokine levels were increased after
      Treg depletion, Tregs mainly affect the NK cell activity in an IL-10-regulated
      pathway. In this study we demonstrate an IL-10-dependent suppression of NK cells
      by activated Tregs during the first days of a retroviral infection.

PMID- 30210500
TI  - Microthrombotic Renal Vascular Lesions Are Associated to Increased Renal
      Inflammatory Infiltration in Murine Lupus Nephritis.
AB  - Background: Vascular microthrombotic lesions in lupus nephritis with or without
      antiphospholipid antibodies may relate to worse renal outcomes. Whether
      microthrombotic lesions are a consequence of renal inflammation or independently
      contribute to renal damage is unclear. Our aim was to investigate the
      relationship between microthrombotic renal vascular lesions and nephritis
      progression in MRL/lpr mice. Methods: MRL/lpr mice were analyzed for the presence
      of renal microvascular, glomerular and tubulointerstitial lesions and the effect
      of anti-aggregation (aspirin or clopidogrel) and dexamethasone on renal clinical
      and pathological manifestations was evaluated. Intravascular platelet aggregates
      (CD41), peri- (F4/80), and intraglomerular (Mac-2) macrophage infiltration, and
      C3 deposition were quantified by immunohistochemistry. Renal function was
      assessed by measuring proteinuria, and serum levels of creatinine and albumin.
      Anti-dsDNA and anti-cardiolipin antibodies, and thromboxane B2 levels were
      quantified by ELISA. Results: Frequency of microthrombotic renal lesions in
      MRL/lpr mice was high and was associated with immune-mediated renal damage.
      Proteinuria positively correlated with glomerular macrophage infiltration and was
      higher in mice with proliferative glomerular lesions. All mice had detectable
      anti-dsDNA and anti-cardiolipin IgG, regardless the presence of microthrombosis.
      Proteinuria and glomerular macrophage infiltration were significantly reduced in
      all treatment groups. Dexamethasone and platelet anti-aggregation similarly
      reduced glomerular damage and inflammation, but only platelet anti-aggregation
      significantly reduced anti-cardiolipin antibodies, renal complement deposition
      and thromboxane B2 levels. Conclusions: Platelet anti-aggregation reduced renal
      inflammatory damage, renal complement deposition, anti-cardiolipin antibodies,
      and thromboxane B2 levels and in MRL/lpr mice, suggesting that platelet
      activation has a pathogenic effect on immune-mediated nephritis. Our results
      point to MRL/lpr mice with lupus nephritis as an appropriate model to analyze the
      potential impact of anti-thrombotic intervention on renal inflammation.

PMID- 30210501
TI  - CRISPR/Cas9 Immunoengineering of Hoxb8-Immortalized Progenitor Cells for
      Revealing CCR7-Mediated Dendritic Cell Signaling and Migration Mechanisms in
      vivo.
AB  - To present antigens to cognate T cells, dendritic cells (DCs) exploit the
      chemokine receptor CCR7 to travel from peripheral tissue via afferent lymphatic
      vessels to directly enter draining lymph nodes through the floor of the
      subcapsular sinus. Here, we combined unlimited proliferative capacity of
      conditionally Hoxb8-immortalized hematopoietic progenitor cells with CRISPR/Cas9
      technology to create a powerful experimental system to investigate DC migration
      and function. Hematopoietic progenitor cells from the bone marrow of Cas9
      transgenic mice were conditionally immortalized by lentiviral transduction
      introducing a doxycycline-regulated form of the transcription factor Hoxb8 (Cas9
      Hoxb8 cells). These cells could be stably cultured for weeks in the presence of
      doxycycline and puromycin, allowing us to introduce additional genetic
      modifications applying CRISPR/Cas9 technology. Importantly, modified Cas9-Hoxb8
      cells retained their potential to differentiate in vitro into myeloid cells, and
      GM-CSF-differentiated Cas9-Hoxb8 cells showed the classical phenotype of GM-CSF
      differentiated bone marrow-derived dendritic cells. Following intralymphatic
      delivery Cas9-Hoxb8 DCs entered the lymph node in a CCR7-dependent manner.
      Finally, we used two-photon microscopy and imaged Cas9-Hoxb8 DCs that expressed
      the genetic Ca2+ sensor GCaMP6S to visualize in real-time chemokine-induced Ca2+
      signaling of lymph-derived DCs entering the LN parenchyma. Altogether, our study
      not only allows mechanistic insights in DC migration in vivo, but also provides a
      platform for the immunoengineering of DCs that, in combination with two-photon
      imaging, can be exploited to further dissect DC dynamics in vivo.

PMID- 30210502
TI  - Up-Regulation of TLR7-Mediated IFN-alpha Production by Plasmacytoid Dendritic
      Cells in Patients With Systemic Lupus Erythematosus.
AB  - Objectives: Aberrant and persistent production of interferon-alpha (IFN-alpha) by
      plasmacytoid dendritic cells (pDCs) is known to play a key role in the
      pathogenesis of systemic lupus erythematosus (SLE). To assess the precise
      function of pDCs in SLE patients, we investigated the differential regulation of
      Toll-like receptor 7 (TLR7) and TLR9 responses during IFN-alpha production by
      pDCs. Methods: Peripheral blood mononuclear cells (PBMCs) in SLE patients without
      hydroxychloroquine treatment, rheumatoid arthritis patients and heathy controls
      were stimulated with TLR7 and TLR9 agonists. To investigate the priming effect by
      cytokines, PBMCs from healthy controls were pre-treated with various cytokines
      and stimulated with TLR7 and TLR9 agonists. The IFN-alpha production in pDCs was
      detected by flow cytometry. Results: TLR7-mediated IFN-alpha production was up
      regulated and correlated positively with disease activity in SLE. Conversely,
      TLR9-mediated IFN-alpha production was down-regulated. Differential regulation of
      TLR7/9 response in SLE was independent of TLR7 and TLR9 expression levels.
      Furthermore, in vitro experiments indicated that TLR7-mediated IFN-alpha
      production was up-regulated by pre-treatment with type I IFN, whereas TLR9
      mediated IFN-alpha production was down-regulated by pre-treatment with type II
      IFN. Conclusions: Our study indicates the association between up-regulation of
      TLR7- mediated IFN-alpha production by pDCs and disease activity and that TLR7
      and TLR9 responses were reversely regulated on pDCs in SLE patients. Thus, type I
      IFN and TLR7-mediated IFN-alpha production were involved in a vicious cycle,
      causing hyper production of IFN-alpha by pDCs during the pathogenic processes of
      SLE.

PMID- 30210503
TI  - The Challenges Imposed by Dengue, Zika, and Chikungunya to Brazil.
AB  - Brazil has a well-established immunization program in which vaccines are provided
      through the Public Health System free of charge to the whole population,
      obtaining high coverage and reducing the incidence of important infectious
      diseases in children and adults. However, the environmental changes and high
      mobility rates of the population occurring in the last decades have triggered the
      sequential introduction of a series of vector-borne emerging infectious diseases,
      such as Dengue, Zika, and Chikungunya, that have imposed a considerable burden on
      the population, with yet unmet solutions. The first to be introduced in Brazil
      was the Dengue virus, reaching epidemic levels in 2010, with over 1 million cases
      annually, maintaining high infection rates until 2016. Brazil has invested in
      vaccine development. The Zika virus infection, initially assumed to have appeared
      during the World Cup in 2014, was later shown to have arrived earlier in 2013.
      Its emergence mobilized the Brazilian scientific community to define priorities
      and strategies, that rapidly investigated mechanisms of pathogenesis,
      differential diagnostics, and determined that Zika virus infection per se causes
      relatively mild symptoms, however, in pregnant women can cause microcephaly in
      the newborns. The diagnostics of Zika infection is confusing given its similar
      symptoms and cross-reactivity with Dengue, which also hindered the appraisal of
      the extent of the epidemics, which peaked in 2015 and finished in 2016. Another
      complicating factor was the overlap with Chikungunya virus infection, which
      arrived in Brazil in 2014, being prevalent in the same regions, with similar
      symptoms to both Dengue and Zika. Although Dengue infection can be fatal and Zika
      infection in pregnant woman can lead to newborns with microcephaly or an array of
      neurodegenerative manifestations, the Chikungunya infection is a debilitating
      disease leaving chronic sequelae, which unfortunately has received less
      attention. Precise differential diagnostics of Dengue, Zika, and Chikungunya will
      be necessary to evaluate the actual extent of each of these diseases during this
      overlapping period. Here we review the impact of these emerging infections on
      public health and how the scientific community was mobilized to deal with them in
      Brazil.

PMID- 30210504
TI  - Host Restriction Factors APOBEC3G/3F and Other Interferon-Related Gene
      Expressions Affect Early HIV-1 Infection in Northern Pig-Tailed Macaque (Macaca
      leonina).
AB  - The northern pig-tailed macaques (NPMs) lack TRIM5alpha, an antiviral restriction
      factor, and instead have TRIM5-CypA. In our previous study, we demonstrated that
      HIV-1NL4-3 successfully infected NPMs and formed a long-term viral reservoir in
      vivo. However, the HIV-1-infected NPMs showed relatively high viremia in the
      first 6 weeks of infection, which declined thereafter suggesting that HIV-1 NL4-3
      infection in these animals was only partly permissive. To optimize HIV-1
      infection in NPMs therefore, we generated HIV-1NL4-R3A and stHIV-1sv, and
      infected NPMs with these viruses. HIV-1NL4-R3A and stHIV-1sv can replicate
      persistently in NPMs during 41 weeks of acute infection stage. Compared to the
      HIV-1NL4-R3A, stHIV-1sv showed a notably higher level of replication, and the
      NPMs infected with the latter induced a more robust neutralizing antibody but a
      weaker cellular immune response. In addition, IFN-I signaling was significantly
      up-regulated with the viral replication, and was higher in the stHIV-1sv infected
      macaques. Consequently, the sequences of pro-viral env showed fewer G-A hyper
      mutations in stHIV-1sv, suggesting that vif gene of SIV could antagonize the
      antiviral effects of APOBEC3 proteins in NPMs. Taken together, NPMs infected with
      HIV-1NL4-R3A and stHIV-1sv show distinct virological and immunological features.
      Furthermore, interferon-related gene expression might play a role in controlling
      primary HIV-1NL4-R3A and stHIV-1sv replication in NPMs. This result suggests NPM
      is a potential HIV/AIDS animal model.

PMID- 30210506
TI  - Application of HTS for Routine Plant Virus Diagnostics: State of the Art and
      Challenges.

PMID- 30210507
TI  - Editorial: The Brassicaceae-Agri-Horticultural and Environmental Perspectives.

PMID- 30210509
TI  - High-Performance Deep Neural Network-Based Tomato Plant Diseases and Pests
      Diagnosis System With Refinement Filter Bank.
AB  - A fundamental problem that confronts deep neural networks is the requirement of a
      large amount of data for a system to be efficient in complex applications.
      Promising results of this problem are made possible through the use of techniques
      such as data augmentation or transfer learning of pre-trained models in large
      datasets. But the problem still persists when the application provides limited or
      unbalanced data. In addition, the number of false positives resulting from
      training a deep model significantly cause a negative impact on the performance of
      the system. This study aims to address the problem of false positives and class
      unbalance by implementing a Refinement Filter Bank framework for Tomato Plant
      Diseases and Pests Recognition. The system consists of three main units: First, a
      Primary Diagnosis Unit (Bounding Box Generator) generates the bounding boxes that
      contain the location of the infected area and class. The promising boxes
      belonging to each class are then used as input to a Secondary Diagnosis Unit (CNN
      Filter Bank) for verification. In this second unit, misclassified samples are
      filtered through the training of independent CNN classifiers for each class. The
      result of the CNN Filter Bank is a decision of whether a target belongs to the
      category as it was detected (True) or not (False) otherwise. Finally, an
      integration unit combines the information from the primary and secondary units
      while keeping the True Positive samples and eliminating the False Positives that
      were misclassified in the first unit. By this implementation, the proposed
      approach is able to obtain a recognition rate of approximately 96%, which
      represents an improvement of 13% compared to our previous work in the complex
      task of tomato diseases and pest recognition. Furthermore, our system is able to
      deal with the false positives generated by the bounding box generator, and class
      unbalances that appear especially on datasets with limited data.

PMID- 30210508
TI  - A High-Density Genetic Map of an Allohexaploid Brassica Doubled Haploid
      Population Reveals Quantitative Trait Loci for Pollen Viability and Fertility.
AB  - A doubled haploid (DH) mapping population was obtained from microspore culture of
      an allohexaploid F1 from the cross between two recently-synthesized allohexaploid
      Brassica lines. We used single nucleotide polymorphism (SNP) genetic variation
      based on restriction-site associated DNA (RAD) sequencing to construct a high
      density genetic linkage map of the population. RAD libraries were constructed
      from the genomic DNA of both parents and 146 DH progenies. A total of 2.87 G
      reads with an average sequencing depth of 2.59 * were obtained in the parents and
      of 1.41 * in the progeny. A total of 290,422 SNPs were identified from clustering
      of RAD reads, from which we developed 7,950 high quality SNP markers that
      segregated normally (1:1) in the population. The linkage map contained all 27
      chromosomes from the parental A, B and C genomes with a total genetic distance of
      5725.19 cM and an average of 0.75 cM between adjacent markers. Genetic distance
      on non-integrated linkage groups was 1534.23 cM, or 21% of total genetic
      distance. Out of 146 DH progenies, 91 had a complete set of 27 chromosomes as
      expected of a hexaploid species, and 21 out of 27 chromosomes showed high
      collinearity between the physical and linkage maps. The loss of chromosome(s) or
      chromosome segment(s) in the DH population was associated with a reduction in
      pollen viability. Twenty-five additive QTL were associated with pollen viability
      and fertility-related traits (seed number, seed yield, pod length, plant height,
      1000-seed weight). In addition, 44 intra-genomic and 18 inter-genomic epistatic
      QTL pairs were detected for 4 phenotypic traits. This provides confidence that
      the DH population may be selected for improved pollen viability and fertility in
      a future allohexaploid Brassica species.

PMID- 30210505
TI  - Type II NKT Cells: An Elusive Population With Immunoregulatory Properties.
AB  - Natural killer T (NKT) cells are unique unconventional T cells that are reactive
      to lipid antigens presented on the non-polymorphic major histocompatibility class
      (MHC) I-like molecule CD1d. They have characteristics of both innate and adaptive
      immune cells, and have potent immunoregulatory roles in tumor immunity,
      autoimmunity, and infectious diseases. Based on their T cell receptor (TCR)
      expression, NKT cells are divided into two subsets, type I NKT cells with an
      invariant TCRalpha-chain (Valpha24 in humans, Valpha14 in mice) and type II NKT
      cells with diverse TCRs. While type I NKT cells are well-studied, knowledge about
      type II NKT cells is still limited, and it is to date only possible to identify
      subsets of this population. However, recent advances have shown that both type I
      and type II NKT cells play important roles in many inflammatory situations, and
      can sometimes regulate the functions of each other. Type II NKT cells can be both
      protective and pathogenic. Here, we review current knowledge on type II NKT cells
      and their functions in different disease settings and how these cells can
      influence immunological outcomes.

PMID- 30210510
TI  - Hydrogen Sulfide: A Gaseous Molecule in Postharvest Freshness.
AB  - Hydrogen sulfide (H2S), as a signaling molecule, is involved in the regulation of
      growth and development in plants. Recent studies have indicated that H2S also
      plays important roles in regulating postharvest senescence of horticultural
      products. The focus of this review is to summarize the synthesis of H2S in plants
      and its potential roles in alleviating the senescence of cut flowers, fruits, and
      vegetables during postharvest storage. During postharvest of horticultural
      products, H2S could scavenge reactive oxygen species via promoting the activity
      of antioxidant enzymes, thereby, sustaining the integrity of the membrane. In
      fruits, H2S effectively enhanced the tolerance of chilling by increasing the
      content of proline and polyphenol compounds. During postharvest storage of
      perishable fruits and vegetables, H2S significantly alleviated decay, which was
      caused by fungi by inhibiting the growth of fungi spores. Moreover, H2S
      interacted with other molecules synergistically (NO) or antagonistically
      (ethylene) to alleviate senescence of horticultural products. At the
      transcriptional level, H2S regulated the expression of senescence-related genes,
      which were related to degradation of proteins and chlorophyll, to delay the
      senescence of horticultural products. Thus, H2S does not only possess positive
      antioxidant and antifungal properties, but also significantly regulates the
      senescence-related gene during postharvest of horticultural products. Future
      studies of H2S in postharvest storage should focus on its molecular mechanism in
      the posttranslational modifications of proteins as well as its safety attributes
      in treated fruits and vegetables.

PMID- 30210511
TI  - Overexpression of a Brix Domain-Containing Ribosome Biogenesis Factor ARPF2 and
      its Interactor ARRS1 Causes Morphological Changes and Lifespan Extension in
      Arabidopsis thaliana.
AB  - The Brix domain is a conserved domain in several proteins involved in ribosome
      biogenesis in yeast and animals. In the Arabidopsis genome, six Brix domain
      containing proteins are encoded; however, their molecular functions have not been
      fully characterized, as yet. Here we report the functional analysis of a Brix
      domain-containing protein, ARPF2, which is homologous to yeast Rpf2 that plays an
      essential role in ribosome biogenesis as a component of the 5S ribonucleoprotein
      particle. By phenotypic characterization of arpf2 mutants, histochemical GUS
      staining, and analysis using green fluorescence protein, we show that ARPF2 is an
      essential and ubiquitously expressed gene encoding a nucleolar protein. Co
      immunoprecipitation and split-GFP-based bimolecular fluorescence complementation
      assays revealed that ARPF2 interacts with a protein named ARRS1, which is
      homologous to yeast Rrs1 that forms a complex with Rpf2 in yeast. Furthermore,
      the result of RNA immunoprecipitation assay indicated that ARPF2 interacts with
      5S ribosomal RNA (rRNA) or the precursor of 5S rRNA, as well as with the internal
      transcribed spacer 2 in the precursors of 25S rRNA. Most intriguingly, we found
      that the overexpression of ARPF2 and ARRS1 leads to characteristic phenotypes,
      including short stem, abnormal leaf morphology, and long lifespan, in
      Arabidopsis. These results suggest that the function of Brix domain-containing
      ARPF2 protein in ribosome biogenesis is intimately associated with the growth and
      development in plants.

PMID- 30210512
TI  - Ectopic Expression of SjCBL1, Calcineurin B-Like 1 Gene From Sedirea japonica,
      Rescues the Salt and Osmotic Stress Hypersensitivity in Arabidopsis cbl1 Mutant.
AB  - Extensive studies with Arabidopsis thaliana suggested that calcineurin B-like
      (CBL) proteins constitute a unique family of calcium sensors in plants, which
      mediate a variety of abiotic stress responses. However, little is known about
      their function in most plants that do not have available genome sequences. In
      this study, we have developed a pair of universal primers that make it possible
      to isolate CBL1-like genes from various plants without sequence information.
      Using these primers, we successfully cloned a full-length cDNA of CBL1-like gene
      in Sedirea japonica (SjCBL1). Bimolecular fluorescence complementation (BiFC) and
      pull-down assays demonstrated that like Arabidopsis CBL1 (AtCBL1), SjCBL1 can
      interacts physically with Arabidopsis CBL-interacting protein kinase 1 (AtCIPK1)
      at the plasma membrane of plant cells in a Ca2+-dependent manner. In addition,
      overexpression of SjCBL1 in the Arabidopsis cbl1 mutant resulted in not only
      rescuing the hypersensitive phenotype toward salt and osmotic stresses, but also
      substantially enhancing the tolerance to them. Taken together, these results
      strongly suggest that SjCBL1 is a functional ortholog of AtCBL1 in Sedirea
      japonica, which can play a critical role in response to salt and osmotic
      stresses. Therefore, it is clear that our findings should significantly
      contribute to broadening and deepening our understanding of the CBL1-mediated
      Ca2+ signaling networks in the plant kingdom.

PMID- 30210514
TI  - Genome-Wide Association Studies of Photosynthetic Traits Related to Phosphorus
      Efficiency in Soybean.
AB  - Photosynthesis is the basis of plant growth and development, and is seriously
      affected by low phosphorus (P) stress. However, few studies have reported for the
      genetic foundation of photosynthetic response to low P stress in soybean. To
      address this issue, 219 soybean accessions were genotyped by 292,035 high-quality
      single nucleotide polymorphisms (SNPs) and phenotyped under normal and low P
      conditions in 2015 and 2016. These datasets were used to identify quantitative
      trait nucleotides (QTNs) for photosynthesis-related traits using mrMLM, ISIS EM
      BLASSO, pLARmEB, FASTmrMLM, FASTmrEMMA, and pKWmEB methods. As a result, 159 QTNs
      within 31 genomic regions were found to be associated with four photosynthesis
      related traits under different P stress conditions. Among the 31 associated
      regions, five (q7-2, q8-1, q9, q13-1, and q20-2) were detected commonly under
      both normal and low P conditions, indicating the insensitivity of these candidate
      genes to low P stress; five were detected only under normal P condition,
      indicating the sensitivity of these candidate genes to low P stress; six were
      detected only under low P condition, indicating the tolerantness of these
      candidate genes to low P stress; 20 were reported in previous studies. Around the
      159 QTNs, 52 candidate genes were mined. These results provide the important
      information for marker-assisted breeding in soybean and further reveal the basis
      for the application of P tolerance to photosynthetic capacity.

PMID- 30210513
TI  - Cork Oak Young and Traumatic Periderms Show PCD Typical Chromatin Patterns but
      Different Chromatin-Modifying Genes Expression.
AB  - Plants are subjected to adverse conditions being outer protective tissues
      fundamental to their survival. Tree stems are enveloped by a periderm made of
      cork cells, resulting from the activity of the meristem phellogen. DNA
      methylation and histone modifications have important roles in the regulation of
      plant cell differentiation. However, studies on its involvement in cork
      differentiation are scarce despite periderm importance. Cork oak periderm
      development was used as a model to study the formation and differentiation of
      secondary protective tissues, and their behavior after traumatic wounding
      (traumatic periderm). Nuclei structural changes, dynamics of DNA methylation, and
      posttranslational histone modifications were assessed in young and traumatic
      periderms, after cork harvesting. Lenticular phellogen producing atypical non
      suberized cells that disaggregate and form pores was also studied, due to high
      impact for cork industrial uses. Immunolocalization of active and repressive
      marks, transcription analysis of the corresponding genes, and correlations
      between gene expression and cork porosity were investigated. During young
      periderm development, a reduction in nuclei area along with high levels of DNA
      methylation occurred throughout epidermis disruption. As cork cells became more
      differentiated, whole nuclei progressive chromatin condensation with accumulation
      in the nuclear periphery and increasing DNA methylation was observed. Lenticular
      cells nuclei were highly fragmented with faint 5-mC labeling. Phellogen nuclei
      were less methylated than in cork cells, and in lenticular phellogen were even
      lower. No significant differences were detected in H3K4me3 and H3K18ac signals
      between cork cells layers, although an increase in H3K4me3 signals was found from
      the phellogen to cork cells. Distinct gene expression patterns in young and
      traumatic periderms suggest that cork differentiation might be under specific
      silencing regulatory pathways. Significant correlations were found between
      QsMET1, QsMET2, and QsSUVH4 gene expression and cork porosity. This work
      evidences that DNA methylation and histone modifications play a role in cork
      differentiation and epidermis induced tension-stress. It also provides the first
      insights into chromatin dynamics during cork and lenticular cells differentiation
      pointing to a distinct type of remodeling associated with cell death.

PMID- 30210516
TI  - OsRAD17 Is Required for Meiotic Double-Strand Break Repair and Plays a Redundant
      Role With OsZIP4 in Synaptonemal Complex Assembly.
AB  - The repair of SPO11-dependent double-strand breaks (DSBs) by homologous
      recombination (HR) ensures the correct segregation of homologous chromosomes. In
      yeast and human, RAD17 is involved in DNA damage checkpoint control and DSB
      repair. However, little is known about its function in plants. In this study, we
      characterized the RAD17 homolog in rice. In Osrad17 pollen mother cells (PMCs),
      associations between non-homologous chromosomes and chromosome fragmentation were
      constantly observed. These aberrant chromosome associations were dependent on the
      formation of programmed DSBs. OsRAD17 interacts with OsRAD1 and the meiotic
      phenotype of Osrad1 Osrad17 is indistinguishable from the two single mutants
      which have similar phenotypes, manifesting they could act in the same pathway.
      OsZIP4, OsMSH5 and OsMER3 are members of ZMM proteins in rice that are required
      for crossover formation. We found that homologous pairing and synapsis, which was
      roughly unaffected in Oszip4 and Osrad17 single mutant, was severely disturbed in
      the Oszip4 Osrad17 double mutant. Similar phenotypes were observed in the Osmsh5
      Osrad17 and Osmer3 Osrad1 double mutants, suggesting the cooperation between the
      checkpoint proteins and ZMM proteins in assuring accurate HR in rice.

PMID- 30210515
TI  - A Transcript and Metabolite Atlas of Blackcurrant Fruit Development Highlights
      Hormonal Regulation and Reveals the Role of Key Transcription Factors.
AB  - Blackcurrant fruit collected at six stages of development were assessed for
      changes in gene expression using custom whole transcriptome microarrays and for
      variation in metabolite content using a combination of liquid chromatography-mass
      spectrometry and gas chromatography-mass spectrometry. Principal components
      analysis demonstrated that fruit development could be clearly defined according
      to their transcript or metabolite profiles. During early developmental stages,
      metabolite profiles were dominated by amino acids and tannins, whilst transcript
      profiles were enriched in functions associated with cell division, anatomical
      structure morphogenesis and cell wall metabolism. During mid fruit development,
      fatty acids accumulated and transcript profiles were consistent with seed and
      embryo development. At the later stages, sugars and anthocyanins accumulated
      consistent with transcript profiles that were associated with secondary
      metabolism. Transcript data also indicated active signaling during later stages
      of fruit development. A targeted analysis of signaling networks revealed a
      dynamic activation and repression of almost 60 different transcripts encoding
      transcription factors across the course of fruit development, many of which have
      been demonstrated as pivotal to controlling such processes in other species.
      Transcripts associated with cytokinin and gibberellin were highly abundant at
      early fruit development, whilst those associated with ABA and ethylene tended to
      be more abundant at later stages. The data presented here provides an insight
      into fruit development in blackcurrant and provides a foundation for further work
      in the elucidation of the genetic basis of fruit quality.

PMID- 30210518
TI  - Effect of Soil Moisture Regimes on Growth and Seed Production of Two Australian
      Biotypes of Sisymbrium thellungii O. E. Schulz.
AB  - Sisymbrium thellungii O. E. Schulz is an emerging problematic weed in the
      northern grain region of Australia. Several different biotypes exist in this
      region but not all biotypes exhibit the same growth and reproduction behavior.
      This might be due to local adaptation to the different agro-ecosystems, however,
      information on this aspect is limited. To determine whether adaptation to water
      stress was a factor in biotype demographic growth and reproduction behavior, we
      evaluated the physiological and biochemical responses of two Australian S.
      thellungii biotypes, selected from high (Dalby) and medium (St. George) rainfall
      areas, to different pot soil moisture levels corresponding to 100, 75, 50, and
      25% of soil water holding capacity (WHC). Averaged across moisture levels, the
      St. George biotype (medium rainfall area) had 89% greater biomass and produced
      321% more seeds than the Dalby biotype. The St. George biotype was less affected
      by increased levels of water stress than the Dalby biotype. The Dalby biotype
      produced 4,787 seeds plant-1 at 100% WHC and only 28 seeds plant-1 at 25% WHC. On
      the other hand, the St. George biotype produced 4,061 seeds plant-1 at 25% WHC
      and its seed production at 100% WHC was 9,834 seeds plant-1. On a per leaf area
      basis and averaged across all moisture levels, the St. George had significantly
      lower net carbon assimilation compared with the Dalby biotype, accompanied by a
      trend for lower stomatal conductance, which might indicate an adaptation to water
      stress. Across the moisture levels, the St. George biotype had higher phenolics
      and total soluble sugar, but free proline content was higher in the Dalby biotype
      compared with the St. George biotype. Like total soluble sugar, proline content
      increased with water stress in both biotypes, but it increased to a greater
      extent in the Dalby biotype, particularly at the 25% of WHC. Branching, flowering
      and maturity occurred earlier in the St. George biotype compared with the Dalby
      biotype, indicating relatively faster growth of the St. George biotype, which
      again seems to be an adaptation to water-limited environments. In conclusion, the
      St. George biotype of S. thellungii had higher reproductive capacity than the
      Dalby biotype across all the moisture regimes, which suggests greater
      invasiveness. Overall, the large size and rapid growth of the S. thellungii
      population from the medium rainfall area, together with its physiological
      response to water stress and its ability to maintain seed production in dry
      conditions, may enable this biotype to become widespread in Australia.

PMID- 30210517
TI  - Comparison of Vacuum MALDI and AP-MALDI Platforms for the Mass Spectrometry
      Imaging of Metabolites Involved in Salt Stress in Medicago truncatula.
AB  - Matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI)
      is routinely used to determine the spatial distributions of various biomolecules
      in tissues. Recently, there has been an increased interest in creating higher
      resolution images using sources with more focused beams. One such source, an
      atmospheric pressure (AP) MALDI source from MassTech, has a laser capable of
      reaching spatial resolutions of 10 MUm. Here, the AP-MALDI source coupled with a
      Q Exactive HF Orbitrap platform is compared to the commercial MALDI LTQ Orbitrap
      XL system using Medicago truncatula root nodules. AP-MALDI parameters, such as
      the S-lens value, capillary temperature, and spray voltage, were optimized on the
      Q Exactive-HF platform for optimal detection of plant metabolites. The
      performance of the two systems was evaluated for sensitivity, spatial resolution,
      and overall ability to detect plant metabolites. The commercial MALDI LTQ
      Orbitrap XL was superior regarding the number of compounds detected, as at least
      two times more m/z were detected compared to the AP-MALDI system. However,
      although the AP-MALDI source requires a spatial resolution higher than 10 MUm to
      get the best signal, the spatial resolution at 30 MUm is still superior compared
      to the 75 MUm spatial resolution achieved on the MALDI platform. The AP-MALDI
      system was also used to investigate the metabolites present in M. truncatula
      roots and root nodules under high salt and low salt conditions. A discriminative
      analysis with SCiLS software revealed m/z ions specific to the control and salt
      conditions. This analysis revealed 44 m/z ions present at relatively higher
      abundances in the control samples, and 77 m/z enriched in the salt samples.
      Liquid chromatography-tandem MS was performed to determine the putative molecular
      identities of some of the mass ions enriched in each sample, including,
      asparagine, adenosine, and nicotianamine in the control samples, and arginine and
      soyasaponin I in the salt treated samples.

PMID- 30210520
TI  - Context-Dependent Developmental Effects of Parental Shade Versus Sun Are Mediated
      by DNA Methylation.
AB  - Parental environment influences progeny development in numerous plant and animal
      systems. Such inherited environmental effects may alter offspring phenotypes in a
      consistent way, for instance when resource-deprived parents produce low quality
      offspring due to reduced maternal provisioning. However, because development of
      individual organisms is guided by both inherited and immediate environmental
      cues, parental conditions may have different effects depending on progeny
      environment. Such context-dependent transgenerational plasticity suggests a
      mechanism of environmental inheritance that can precisely interact with immediate
      response pathways, such as epigenetic modification. We show that parental light
      environment (shade versus sun) resulted in context-dependent effects on seedling
      development in a common annual plant, and that these effects were mediated by DNA
      methylation. We grew replicate parents of five highly inbred Polygonum persicaria
      genotypes in glasshouse shade versus sun and, in a fully factorial design,
      measured ecologically important traits of their isogenic seedling offspring in
      both environments. Compared to the offspring of sun-grown parents, the offspring
      of shade-grown parents produced leaves with greater mean and specific leaf area,
      and had higher total leaf area and biomass. These shade-adaptive effects of
      parental shade were pronounced and highly significant for seedlings growing in
      shade, but slight and generally non-significant for seedlings growing in sun.
      Based on both regression and covariate analysis, inherited effects of parental
      shade were not mediated by changes to seed provisioning. To test for a role of
      DNA methylation, we exposed replicate offspring of isogenic shaded and fully
      insolated parents to either the demethylating agent zebularine or to control
      conditions during germination, then raised them in simulated growth chamber
      shade. Partial demethylation of progeny DNA had no phenotypic effect on offspring
      of shaded parents, but caused offspring of sun-grown parents to develop as if
      their parents had been shaded, with larger leaves and greater total canopy area
      and biomass. These results contribute to the increasing body of evidence that DNA
      methylation can mediate transgenerational environmental effects, and show that
      such effects may contribute to nuanced developmental interactions between
      parental and immediate environments.

PMID- 30210521
TI  - Delivery of Hairpin RNAs and Small RNAs Into Woody and Herbaceous Plants by Trunk
      Injection and Petiole Absorption.
AB  - Since its discovery, RNA interference has been widely used in crop protection.
      Recently, transgene-free procedures that were based on exogenous application of
      RNA molecules having the capacity to trigger RNAi in planta have been reported.
      Yet, efficient delivery of such RNA molecules to plants and particularly to trees
      poses major technical challenges. Here, we describe simple methods for efficient
      delivery of hairpin RNAs (hpRNAs) and small interfering RNAs (siRNAs) to Malus
      domestica, Vitis vinifera, and Nicotiana benthamiana that are based on trunk
      injection and/or petiole absorption. The applied RNA molecules were efficiently
      taken up and systemically transported. In apical leaves, the RNA was already
      detectable 1 day post-application (dpa) and could be detected at least up to 10
      dpa, depending on the method of application. Confocal microscopy revealed that
      the uptaken and systemically transported RNA molecules were strictly restricted
      to the xylem and apoplast which may illustrate why the applied hpRNAs were not
      processed into siRNAs by plant DICER-LIKE (DCL) endonucleases. These innovative
      methods may have great impact in pest management against chewing and/or xylem sap
      feeding vectors and eukaryotic pathogens that reside in the xylem.

PMID- 30210522
TI  - Abscisic Acid Regulates Anthocyanin Biosynthesis and Gene Expression Associated
      With Cell Wall Modification in Ripening Bilberry (Vaccinium myrtillus L.) Fruits.
AB  - Ripening of non-climacteric bilberry (Vaccinium myrtillus L.) fruit is
      characterized by a high accumulation of health-beneficial anthocyanins. Plant
      hormone abscisic acid (ABA) and sucrose have been shown to be among the central
      signaling molecules coordinating non-climacteric fruit ripening and anthocyanin
      accumulation in some fruits such as strawberry. Our earlier studies have
      demonstrated an elevation in endogenous ABA level in bilberry fruit at the onset
      of ripening indicating a role for ABA in the regulation of bilberry fruit
      ripening. In the present study, we show that the treatment of unripe green
      bilberry fruits with exogenous ABA significantly promotes anthocyanin
      biosynthesis and accumulation both in fruits attached and detached to the plant.
      In addition, ABA biosynthesis inhibitor, fluridone, delayed anthocyanin
      accumulation in bilberries. Exogenous ABA also induced the expression of several
      genes involved in cell wall modification in ripening bilberry fruits.
      Furthermore, silencing of VmNCED1, the key gene in ABA biosynthesis, was
      accompanied by the down-regulation in the expression of key anthocyanin
      biosynthetic genes. In contrast, the treatment of unripe green bilberry fruits
      with exogenous sucrose or glucose did not lead to an enhancement in the
      anthocyanin accumulation neither in fruits attached to plant nor in post-harvest
      fruits. Moreover, sugars failed to induce the expression of genes associated in
      anthocyanin biosynthesis or ABA biosynthesis while could elevate expression of
      some genes associated with cell wall modification in post-harvest bilberry
      fruits. Our results demonstrate that ABA plays a major role in the regulation of
      ripening-related processes such as anthocyanin biosynthesis and cell wall
      modification in bilberry fruit, whereas sugars seem to have minor regulatory
      roles in the processes. The results indicate that the regulation of bilberry
      fruit ripening differs from strawberry that is currently considered as a model of
      non-climacteric fruit ripening. In this study, we also identified transcription
      factors, which expression was enhanced by ABA, as potential regulators of ABA
      mediated bilberry fruit ripening processes.

PMID- 30210519
TI  - Using Biotechnology-Led Approaches to Uplift Cereal and Food Legume Yields in
      Dryland Environments.
AB  - Drought and heat in dryland agriculture challenge the enhancement of crop
      productivity and threaten global food security. This review is centered on
      harnessing genetic variation through biotechnology-led approaches to select for
      increased productivity and stress tolerance that will enhance crop adaptation in
      dryland environments. Peer-reviewed literature, mostly from the last decade and
      involving experiments with at least two seasons' data, form the basis of this
      review. It begins by highlighting the adverse impact of the increasing intensity
      and duration of drought and heat stress due to global warming on crop
      productivity and its impact on food and nutritional security in dryland
      environments. This is followed by (1) an overview of the physiological and
      molecular basis of plant adaptation to elevated CO2 (eCO2), drought, and heat
      stress; (2) the critical role of high-throughput phenotyping platforms to study
      phenomes and genomes to increase breeding efficiency; (3) opportunities to
      enhance stress tolerance and productivity in food crops (cereals and grain
      legumes) by deploying biotechnology-led approaches [pyramiding quantitative trait
      loci (QTL), genomic selection, marker-assisted recurrent selection, epigenetic
      variation, genome editing, and transgene) and inducing flowering independent of
      environmental clues to match the length of growing season; (4) opportunities to
      increase productivity in C3 crops by harnessing novel variations (genes and
      network) in crops' (C3, C4) germplasm pools associated with increased
      photosynthesis; and (5) the adoption, impact, risk assessment, and enabling
      policy environments to scale up the adoption of seed-technology to enhance food
      and nutritional security. This synthesis of technological innovations and
      insights in seed-based technology offers crop genetic enhancers further
      opportunities to increase crop productivity in dryland environments.

PMID- 30210523
TI  - Effects of Geological and Environmental Events on the Diversity and Genetic
      Divergence of Four Closely Related Pines: Pinus koraiensis, P. armandii, P.
      griffithii, and P. pumila.
AB  - The effects of mountain uplift and environmental oscillations on nucleotide
      variability and species divergence remain largely unknown in East Asia. In this
      study, based on multiple nuclear DNA markers, we investigated the levels and
      patterns of nucleotide diversity and interspecific divergence in four closely
      related pines in China, i.e., Pinus koraiensis, P. armandii, P. griffithii, and
      P. pumila. The four pine taxa shared low levels of nucleotide polymorphisms at
      the species level. P. pumila had the highest silent nucleotide diversity (pisil =
      0.00661) whereas P. griffithii had the lowest (pisil = 0.00175), while the levels
      of genetic polymorphism in P. armandii (pisil = 0.00508) and P. koraiensis (pisil
      = 0.00652) were intermediate between the other two species. Population genetic
      structure analysis showed that variations primarily existed within populations of
      the four pine species, presumably due to habitat fragmentation or the island-like
      distributions of Pinus species. Population divergence (FST) analysis showed that
      the genetic divergence between P. griffithii and P. koraiensis was much greater
      than that between P. koraiensis and the other two pines species. Isolation-with
      migration analysis suggested that asymmetric gene flow had occurred between any
      two pairs of pine species. Phylogenetic analyses indicated that the four allied
      species split into two groups about 1.37 million years ago, where P. armandii and
      P. pumila were closer and clustered as sister species, whereas P. koraiensis and
      P. griffithii were clustered on another branch. Our results and those obtained in
      previous studies suggest that mountain uplift and geological climate oscillations
      may have led to the patterns of genetic divergence and nucleotide variations in
      these four pine species.

PMID- 30210524
TI  - Suppressed Recombination of Sex Chromosomes Is Not Caused by Chromosomal
      Reciprocal Translocation in Spiny Frog (Quasipaa boulengeri).
AB  - Chromosome rearrangements (CRs) are perceived to be related to sex chromosome
      evolution, but it is a matter of controversy whether CRs are the initial
      causative mechanism of suppressed recombination for sex differentiation. The
      early stages of sex chromosome evolution in amphibians may represent intermediate
      states of differentiation, and if so, they potentially shed light on the ultimate
      cause of suppressed recombination and the role of CRs in sex chromosome
      differentiation. In this paper, we showed that sex determination differs among 16
      populations of spiny frog (Quasipaa boulengeri), in which individuals have normal
      and rearranged chromosomes caused by reciprocal translocation. In eastern areas,
      without translocation, genetic differentiation between sexes was relatively low,
      suggesting unrestricted recombination. In comparison, in western populations that
      have both normal and translocated chromosomes, a male-heterogametic system and
      lack of X-Y recombination were identified by male-specific alleles and
      heterozygote excess. However, such genetic differentiation between sexes in
      western populations was not directly related to karyotypes, as it was found in
      individuals with both normal and translocated karyotypes. In the western Sichuan
      Basin, male-specific and translocation-specific allelic frequency distributions
      suggested that recombination of sex-differentiation ceased in all populations,
      but recombination suppression caused by translocation did not exist in some
      populations. Combined with phylogenetic inference, this indicated that the
      establishment of sex-linkage had taken place independently of reciprocal
      translocation, and translocation was not the ultimate cause of sex chromosome
      differentiation. Furthermore, comparison of the genetic diversity of alleles on Y
      chromosomes, X chromosomes, and autosomes in western populations showed a
      reduction of effective population size on sex chromosomes, which may be caused by
      reciprocal translocation. It indicates that, although it is not the ultimate
      cause of recombination suppression, reciprocal translocation may enhance sex
      chromosome differentiation.

PMID- 30210525
TI  - Regional Differences and Similarities in the Brain Transcriptome for Mice
      Selected for Ethanol Preference From HS-CC Founders.
AB  - The high genetic complexity found in heterogeneous stock (HS-CC) mice, together
      with selective breeding, can be used to detect new pathways and mechanisms
      associated with ethanol preference and excessive ethanol consumption. We
      predicted that these pathways would provide new targets for therapeutic
      manipulation. Previously (Colville et al., 2017), we observed that preference
      selection strongly affected the accumbens shell (SH) genes associated with
      synaptic function and in particular genes associated with synaptic tethering.
      Here we expand our analyses to include substantially larger sample sizes and
      samples from two additional components of the "addiction circuit," the central
      nucleus of the amygdala (CeA) and the prelimbic cortex (PL). At the level of
      differential expression (DE), the majority of affected genes are region-specific;
      only in the CeA did the DE genes show a significant enrichment in GO annotation
      categories, e.g., neuron part. In all three brain regions the differentially
      variable genes were significantly enriched in a single network module
      characterized by genes associated with cell-to-cell signaling. The data point to
      glutamate plasticity as being a key feature of selection for ethanol preference.
      In this context the expression of Dlg2 which encodes for PSD-93 appears to have a
      key role. It was also observed that the expression of the clustered
      protocadherins was strongly associated with preference selection.

PMID- 30210526
TI  - DECtp: Calling Differential Gene Expression Between Cancer and Normal Samples by
      Integrating Tumor Purity Information.
AB  - Identifying differentially expressed genes (DEGs) between tumor and normal
      samples is critical for studying tumorigenesis, and has been routinely applied to
      identify diagnostic, prognostic, and therapeutic biomarkers for many cancers. It
      is well-known that solid tumor tissue samples obtained from clinical settings are
      always mixtures of cancer and normal cells. However, the tumor purity information
      is more or less ignored in traditional differential expression analyses, which
      might decrease the power of differential gene identification or even bias the
      results. In this paper, we have developed a novel differential gene calling
      method called DECtp by integrating tumor purity information into a generalized
      least square procedure, followed by the Wald test. We compared DECtp with popular
      methods like t-test and limma on nine simulation datasets with different sample
      sizes and noise levels. DECtp achieved the highest area under curves (AUCs) for
      all the comparisons, suggesting that cancer purity information is critical for
      DEG calling between tumor and normal samples. In addition, we applied DECtp into
      cancer and normal samples of 14 tumor types collected from The Cancer Genome
      Atlas (TCGA) and compared the DEGs with those called by limma. As a result, DECtp
      achieved more sensitive, consistent, and biologically meaningful results and
      identified a few novel DEGs for further experimental validation.

PMID- 30210528
TI  - QTL Mapping and Marker Identification for Sex-Determining: Indicating XY Sex
      Determination System in the Swimming Crab (Portunus trituberculatus).
AB  - Sex determination is an important area of research, which has always had an
      intriguing aspect in evolutionary and developmental biology. Quantitative trait
      locus (QTL) mapping for sex will be helpful in clarifying the sex determination
      system. In this study, the sex QTL mapping of the swimming crab (Portunus
      trituberculatus) was performed based on a high-density linkage map, and a highly
      significant QTL specifically mapped on a single linkage group (LG) was firstly
      identified (LG24, LOD > 14). Twenty markers in the QTL region showed significant
      associations with sex by association analysis, of which heterogametic genotypes
      in males supported the XY sex determination mechanism. Two sex-specific markers
      at the family level were identified via segregation distortion analysis, which
      were known to be the most closely linked to the sex of P. trituberculatus. Based
      on sex marker sequences (Marker3840, Marker20320, and Marker10494), three
      potential sex-related genes were identified, and the quantitative real-time PCR
      results suggested that these genes were important in spermatogenesis or sex
      characteristics in males. Our results will contribute to the fine-mapping of sex
      determining genes and clarify the sex determination mechanism of P.
      trituberculatus.

PMID- 30210527
TI  - Distinct Roles for Two Chromosome 1 Loci in Ethanol Withdrawal, Consumption, and
      Conditioned Place Preference.
AB  - We previously identified a region on chromosome 1 that harbor quantitative trait
      loci (QTLs) with large effects on alcohol withdrawal risk using both chronic and
      acute models in mice. Here, using newly created and existing QTL interval
      specific congenic (ISC) models, we report the first evidence that this region
      harbors two distinct alcohol withdrawal QTLs (Alcw11and Alcw12), which underlie
      13% and 3-6%, respectively, of the genetic variance in alcohol withdrawal
      severity measured using the handling-induced convulsion. Our results also
      precisely localize Alcw11 and Alcw12 to discreet chromosome regions (syntenic
      with human 1q23.1-23.3) that encompass a limited number of genes with validated
      genotype-dependent transcript expression and/or non-synonymous sequence variation
      that may underlie QTL phenotypic effects. ISC analyses also implicate Alcw11and
      Alcw12 in withdrawal-induced anxiety-like behavior, representing the first
      evidence for their broader roles in alcohol withdrawal beyond convulsions; but
      detect no evidence for Alcw12 involvement in ethanol conditioned place preference
      (CPP) or consumption. Our data point to high-quality candidates for Alcw12,
      including genes involved in mitochondrial respiration, spatial buffering, and
      neural plasticity, and to Kcnj9 as a high-quality candidate for Alcw11. Our
      studies are the first to show, using two null mutant models on different genetic
      backgrounds, that Kcnj9-/- mice demonstrate significantly less severe alcohol
      withdrawal than wildtype littermates using acute and repeated exposure paradigms.
      We also demonstrate that Kcnj9-/- voluntarily consume significantly more alcohol
      (20%, two-bottle choice) than wildtype littermates. Taken together with evidence
      implicating Kcnj9 in ethanol CPP, our results support a broad role for this locus
      in ethanol reward and withdrawal phenotypes. In summary, our results demonstrate
      two distinct chromosome 1 QTLs that significantly affect risk for ethanol
      withdrawal, and point to their distinct unique roles in alcohol reward
      phenotypes.

PMID- 30210529
TI  - Impact of FMR1 Premutation on Neurobehavior and Bioenergetics in Young
      Monozygotic Twins.
AB  - Mitochondrial dysfunction (MD) has been identified in lymphocytes, fibroblasts
      and brain samples from adults carrying a 55-200 CGG expansion in the fragile X
      mental retardation 1 (FMR1) gene (premutation; PM); however, limited data are
      available on the bioenergetics of pediatric carriers. Here we discuss a case
      report of three PM carriers: two monozygotic twins (aged 8 years) harboring an
      FMR1 allele with 150-180 CGG repeats, with no cognitive or intellectual issues
      but diagnosed with depression, mood instability and ADHD, and their mother
      (asymptomatic carrier with 78 CGG repeats). Fibroblasts and lymphocytes from the
      twins presented a generalized OXPHOS deficit, altered mitochondrial network,
      accumulation of depolarized mitochondria, and increased mitochondrial ROS
      production, outcomes distinct and more severe than the mother's ones, suggesting
      the involvement of modulatory effects mediated by CGG expansion, X-activation
      ratio, sex hormones and epigenetic factors (chronic inflammation, consequence of
      Lyme disease). The degree of the severity of MD appeared to segregate with the
      morbidity of the phenotype. The mitochondrial ROS-mediated HIF-1alpha
      stabilization was identified as a key player at contributing to the MD, pointing
      it as a novel target for future therapeutical intervention.

PMID- 30210533
TI  - Deep Convolutional Neural Network Used in Single Sample per Person Face
      Recognition.
AB  - Face recognition (FR) with single sample per person (SSPP) is a challenge in
      computer vision. Since there is only one sample to be trained, it makes facial
      variation such as pose, illumination, and disguise difficult to be predicted. To
      overcome this problem, this paper proposes a scheme combined traditional and deep
      learning (TDL) method to process the task. First, it proposes an expanding sample
      method based on traditional approach. Compared with other expanding sample
      methods, the method can be used easily and conveniently. Besides, it can generate
      samples such as disguise, expression, and mixed variation. Second, it uses
      transfer learning and introduces a well-trained deep convolutional neural network
      (DCNN) model and then selects some expanding samples to fine-tune the DCNN model.
      Third, the fine-tuned model is used to implement experiment. Experimental results
      on AR face database, Extend Yale B face database, FERET face database, and LFW
      database demonstrate that TDL achieves the state-of-the-art performance in SSPP
      FR.

PMID- 30210530
TI  - Epigenetic Mechanisms Link Maternal Diets and Gut Microbiome to Obesity in the
      Offspring.
AB  - Nutrition is the most important environmental factor that can influence early
      developmental processes through regulation of epigenetic mechanisms during
      pregnancy and neonatal periods. Maternal diets or nutritional compositions
      contribute to the establishment of the epigenetic profiles in the fetus that have
      a profound impact on individual susceptibility to certain diseases or disorders
      in the offspring later in life. Obesity is considered a global epidemic that
      impairs human life quality and also increases risk of development of many human
      diseases such as diabetes and cardiovascular diseases. Studies have shown that
      maternal nutrition status is closely associated with obesity in progenies
      indicating obesity has a developmental origin. Maternal diets may also impact the
      early establishment of the fetal and neonatal microbiome leading to specific
      epigenetic signatures that may potentially predispose to the development of late
      life obesity. This article will review the association of different maternal
      dietary statuses including essential nutritional quantity and specific dietary
      components with gut microbiome in determining epigenetic impacts on offspring
      susceptibility to obesity.

PMID- 30210534
TI  - A Biologically Inspired Approach for Robot Depth Estimation.
AB  - Aimed at building autonomous service robots, reasoning, perception, and action
      should be properly integrated. In this paper, the depth cue has been analysed as
      an early stage given its importance for robotic tasks. So, from neuroscience
      findings, a hierarchical four-level dorsal architecture has been designed and
      implemented. Mainly, from a stereo image pair, a set of complex Gabor filters is
      applied for estimating an egocentric quantitative disparity map. This map leads
      to a quantitative depth scene representation that provides the raw input for a
      qualitative approach. So, the reasoning method infers the data required to make
      the right decision at any time. As it will be shown, the experimental results
      highlight the robust performance of the biologically inspired approach presented
      in this paper.

PMID- 30210531
TI  - The Telomerase Complex Directly Controls Hematopoietic Stem Cell Differentiation
      and Senescence in an Induced Pluripotent Stem Cell Model of Telomeropathy.
AB  - Telomeropathies are rare disorders associated with impaired telomere length
      control mechanisms that frequently result from genetic mutations in the
      telomerase complex. Dyskeratosis congenita is a congenital progressive
      telomeropathy in which mutation in the telomerase RNA component (TERC) impairs
      telomere maintenance leading to accelerated cellular senescence and clinical
      outcomes resembling premature aging. The most severe clinical feature is
      perturbed hematopoiesis and bone-marrow failure, but the underlying mechanisms
      are not fully understood. Here, we developed a model of telomerase function
      imbalance using shRNA to knockdown TERC expression in human induced pluripotent
      stem cells (iPSCs). We then promoted in vitro hematopoiesis in these cells to
      analyze the effects of TERC impairment. Reduced TERC expression impaired
      hematopoietic stem-cell (HSC) differentiation and increased the expression of
      cellular senescence markers and production of reactive oxygen species.
      Interestingly, telomere length was unaffected in shTERC knockdown iPSCs, leading
      to conclusion that the phenotype is controlled by non-telomeric functions of
      telomerase. We then assessed the effects of TERC-depletion in THP-1 myeloid cells
      and again observed reduced hematopoietic and myelopoietic differentiative
      potential. However, these cells exhibited impaired telomerase activity as
      verified by accelerated telomere shortening. shTERC-depleted iPSC-derived and THP
      1-derived myeloid precursors had lower phagocytic capacity and increased ROS
      production, indicative of senescence. These findings were confirmed using a
      BIBR1532 TERT inhibitor, suggesting that these phenotypes are dependent on
      telomerase function but not directly linked to telomere length. These data
      provide a better understanding of the molecular processes driving the clinical
      signs of telomeropathies and identify novel roles of the telomerase complex other
      than regulating telomere length.

PMID- 30210535
TI  - Safety of Propofol versus Nonpropofol-Based Sedation in Children Undergoing
      Gastrointestinal Endoscopy: A Systematic Review and Meta-Analysis.
AB  - Background: The majority of children who undergo gastrointestinal (GI) endoscopy
      require anesthesia or procedural sedation for comfort, cooperation, and procedure
      efficiency. The safety profile of propofol is not well established in children
      but has been studied in the literature. Objective: The aim of this study is to
      evaluate and compare the safety of propofol-only sedation for GI endoscopy
      procedures to other anesthetic regimes in the pediatric population. Methods: A
      search was conducted in the MEDLINE, Embase, and Cochrane Library databases.
      Randomized clinical trials and prospective cohorts were included in the study.
      Results: No significant difference was noted in total complications between the
      two cohorts with a pooled OR of 1.31 (95% CI: 0.57-3.04, chi2 = 0.053, I2 =
      54.31%). The pooled rate of complications in the studies was 23.4% for those
      receiving propofol only and 18.2% for those receiving other anesthetic regimens.
      Sensitivity analysis was performed removing a study with a very different control
      comparison compared to the rest of the studies included. Once excluded, there was
      minimal heterogeneity in the remaining studies and a significant difference in
      overall complications was detected, with more complications seen in the propofol
      only group compared to the other anesthetic groups (OR 1.87, 95% CI 1.09-3.20).
      Conclusion: Significantly higher incidence of cardiorespiratory complications was
      noted in the propofol-only versus other anesthetic regimens in pediatric patients
      undergoing GI endoscopy in this meta-analysis. However, the overall quality of
      the evidence is very low. How to Apply This Knowledge for Routine Clinical
      Practice: Clinicians providing sedation to a pediatric population for GI
      endoscopy should consider there may be increased risks when using a propofol-only
      regimen, but further study is needed.

PMID- 30210532
TI  - Sinorhizobium meliloti RNase III: Catalytic Features and Impact on Symbiosis.
AB  - Members of the ribonuclease (RNase) III family of enzymes are metal-dependent
      double-strand specific endoribonucleases. They are ubiquitously found and
      eukaryotic RNase III-like enzymes include Dicer and Drosha, involved in RNA
      processing and RNA interference. In this work, we have addressed the primary
      characterization of RNase III from the symbiotic nitrogen-fixing alpha
      proteobacterium Sinorhizobium meliloti. The S. meliloti rnc gene does encode an
      RNase III-like protein (SmRNase III), with recognizable catalytic and double
      stranded RNA (dsRNA)-binding domains that clusters in a branch with its alpha
      proteobacterial counterparts. Purified SmRNase III dimerizes, is active at
      neutral to alkaline pH and behaves as a strict metal cofactor-dependent double
      strand endoribonuclease, with catalytic features distinguishable from those of
      the prototypical member of the family, the Escherichia coli ortholog (EcRNase
      III). SmRNase III prefers Mn2+ rather than Mg2+ as metal cofactor, cleaves the
      generic structured R1.1 substrate at a site atypical for RNase III cleavage, and
      requires higher cofactor concentrations and longer dsRNA substrates than EcRNase
      III for optimal activity. Furthermore, the ultraconserved E125 amino acid was
      shown to play a major role in the metal-dependent catalysis of SmRNase III.
      SmRNase III degrades endogenous RNA substrates of diverse biogenesis with
      different efficiency, and is involved in the maturation of the 23S rRNA. SmRNase
      III loss-of-function neither compromises viability nor alters morphology of S.
      meliloti cells, but influences growth, nodulation kinetics, the onset of nitrogen
      fixation and the overall symbiotic efficiency of this bacterium on the roots of
      its legume host, alfalfa, which ultimately affects plant growth. Our results
      support an impact of SmRNase III on nodulation and symbiotic nitrogen fixation in
      plants.

PMID- 30210536
TI  - Development and Validation of the Coeliac Disease Food Attitudes and Behaviours
      Scale.
AB  - Objectives: Previous studies on coeliac disease suggest that attitudes towards
      the gluten-free diet may contribute to the development of disordered eating. This
      study describes the development and validation of the Coeliac Disease Food
      Attitudes and Behaviours scale (CD-FAB) to measure these behaviours in coeliac
      disease. Research Methods and Procedures: Focus groups were used to develop 33
      potential questionnaire items. These items were reviewed by service users and
      then distributed online to 157 adults with coeliac disease. Items were removed
      based on ceiling/floor effects, high interitem correlations (>0.7) and factor
      analysis. 11 items were retained. Exploratory factor analysis was then conducted.
      The psychometric properties of the final version of the CD-FAB were assessed via
      using an online platform. Results: The CD-FAB had 11 items distributed across one
      factor assessing attitudes and behaviours towards food. These factors explained
      44.1% of the variance in responding. The CD-FAB and its subscales had high
      internal consistency (Cronbach's alpha > 0.7) and psychometric validation
      indicated good convergent and discriminant validity. High scores on the CD-FAB
      are associated with psychological distress and an impaired quality of life.
      Conclusions: The CD-FAB is a reliable and valid measure of food attitudes and
      behaviours in coeliac disease. As a new disease-specific instrument, it may be a
      useful tool for evaluating food concerns in individuals with coeliac disease in a
      clinical setting and for further exploring the development of disordered eating
      patterns in coeliac disease. Further research is required to assess the full
      potential of the CD-FAB.

PMID- 30210538
TI  - Germ Cell Tumors: Updates on Epidemiology, Biology, and Treatment Considerations.

PMID- 30210537
TI  - Cytotoxicity of the Aqueous Extract and Organic Fractions from Origanum majorana
      on Human Breast Cell Line MDA-MB-231 and Human Colon Cell Line HT-29.
AB  - The toxicity of the aqueous extract of Origanum majorana was tested (5 and 10
      g/kg) in albino mice. No symptoms of toxicity or mortality were observed. The
      mice survived being active and healthy during all 14 days of observation. In
      addition, the weight measurement of the left and right kidneys, heart, and liver
      shows no significant difference between the control, 5 g/kg, and 10 g/kg. All
      extracts (aqueous, petroleum ether, dichloromethane, ethyl acetate, methanolic,
      and depleted aqueous extracts) of Origanum majorana tested against both types of
      cancer cells showed a more pronounced cytotoxic effect against breast cell line
      MDA-MB-231 than colon cells line HT-29 cells. The most marked effect is that of
      the ethyl acetate extract with IC50 30.90 +/- 1.39 and 50.11 +/- 1.44 (ug/ml),
      respectively. HPLC analysis of extracts from Origanum majorana showed that this
      plant contained polyphenols and flavonoids, which may be responsible for the
      biological activities found.

PMID- 30210539
TI  - Artemisinin-Based Combination Therapy Depressed Mitosis and Induced Chromosome
      Aberration in Onion Root Cells.
AB  - Artemisinin-based combination therapy is used to treat uncomplicated malaria
      disease in most endemic countries. Although most antimalarial drugs are effective
      in killing the parasite, there is a concern of induced toxicity to the cell.
      Here, the cytogenotoxicity of dihydroartemisinin-piperaquine phosphate (DHAP), a
      coformulation for artemisinin-based combination therapy, was evaluated using
      Allium cepa model. The toxicity on the mitotic index varies with the duration of
      exposure and dose tested. Chromosome aberrations observed include chromosome
      fragments, chromosome bridges, binucleated cells, and micronucleated cells. This
      study showed that DHAP can depress mitosis and induce chromosome abnormalities.
      Their accumulation in cells may be inhibitory to cell division and growth. This
      calls for caution in the administration of artemisinin combination therapy for
      the treatment of malaria ailment. Wide spacing of dosage is therefore suggested
      in order to avoid the risk of genetic damage.

PMID- 30210540
TI  - Comment on "The Gut Microbiome Profile in Obesity: A Systematic Review".

PMID- 30210541
TI  - Facile Analytical Methods to Determine the Purity of Titanium Tetrachloride.
AB  - We propose a simple method to investigate both the qualitative and quantitative
      properties of titanium tetrachloride. The selection and concentration of the
      employed solvent were found to be very important in the analysis of highly
      reactive titanium tetrachloride (TiCl4). Herein, we employed various
      concentrations of an acid solution to serve as a stabilizing medium. Qualitative
      analysis was performed via Fourier transform-infrared spectroscopy (FT-IR) and
      scanning electron microscope-energy dispersive spectroscopy (SEM-EDS).
      Additionally, the quantitative analysis was performed via inductively coupled
      plasma optical emission spectroscopy (ICP-OES). We concluded that both the
      qualitative and quantitative properties of titanium tetrachloride could be easily
      measured using a specific acidic solvent as a medium.

PMID- 30210542
TI  - Effects of Different Methods of Isolation on Volatile Composition of Artemisia
      annua L.
AB  - In order to determine influence of extraction method on volatile oil composition
      of Artemisia annua L., steam distillation, hydrodistillation, organic solvent
      extraction, and headspace sampling have been applied. The relative abundance of
      volatile compounds from the odorous aerial parts of A. annua, obtained by
      different extraction techniques, was analyzed by GC-MS. Exactly fifty
      constituents were identified. The leaf and flower essential oil yield ranged from
      0.9 to 2.3% (v/w). Oxygenated monoterpenes were predominant in all samples ranged
      from 42.6% for steam-distilled fraction of petroleum ether extract to 70.6% for
      headspace of plant material. Essential oils isolated by steam distillation and
      hydrodistillation indicate that A. annua belongs to artemisia ketone chemotype
      with its relative content of 30.2% and 28.3%, respectively. The principal
      constituent in headspace sample of plant material was also artemisia ketone
      (46.4%), while headspace of petroleum ether extract had camphene (25.6%) as the
      major compound. The results prove the combined approaches to be powerful for the
      analysis of complex herbal samples.

PMID- 30210544
TI  - Experimental Investigations into the Mechanical, Tribological, and Corrosion
      Properties of Hybrid Polymer Matrix Composites Comprising Ceramic Reinforcement
      for Biomedical Applications.
AB  - Hybrid polymer matrix composites (HPMC) are prominent material for the formation
      of biomaterial and offer various advantages such as low cost, high strength, and
      the fact that they are easy to manufacture. However, they are associated with low
      mechanical (low hardness) and tribological properties (high wear rate). The
      average hip joint load fluctuates between three to five times of the body weight
      during jumping and jogging and depends on various actions relating to body
      positions. Alternate bone and prosthesis material plays a critical role in
      attaining strength as it determines the method of load transferred to the system.
      The material property called modulus of elasticity is an important design
      variable during the selection of the geometry and design methodology. The present
      work is demonstrated on how to improve the properties of high-density
      polyethylene (HDPE) substantially by the addition of bioceramic fillers such as
      titanium oxide (TiO2) and alumina (Al2O3). The volume fractions of Al2O3 and TiO2
      are limited to 20% and 10%, respectively. Samples were fabricated as per ASTM
      standards using an injection moulding machine and various properties such as
      mechanical (tensile, flexural, and impact), tribological (hardness, wear), and
      corrosion including SEM, density, and fractography analysis studied. Experimental
      results revealed that an injection moulding process is suitable for producing
      defect-free mould HPMC. HPMC comprising 70% HDPE/20% Al2O3/10% TiO2 has proved
      biocompatible and a substitute for biomaterial. A substantial increase in the
      mechanical and tribological properties and full resistance to corrosion makes
      HPMC suitable for use in orthopaedic applications such as human bone replacement,
      bone fixation plates, hip joint replacement, bone cement, and bone graft in bone
      surgery.

PMID- 30210543
TI  - Extracts of Clove (Syzygium aromaticum) Potentiate FMSP-Nanoparticles Induced
      Cell Death in MCF-7 Cells.
AB  - Both nanoparticles and cloves (Syzygium aromaticum) possess anticancer
      properties, but they do not elicit a significant response on cancer cells when
      treated alone. In the present study, we have tested fluorescent magnetic
      submicronic polymer nanoparticles (FMSP-nanoparticles) in combination with crude
      clove extracts on human breast cancer cells (MCF-7) to examine whether the
      combination approach enhance the cancer cell death. The MCF-7 cells were treated
      with different concentrations (1.25 MUg/mL, 12.5 MUg/mL, 50 MUg/mL, 75 MUg/mL,
      and 100 MUg/mL) of FMSP-nanoparticles alone and in combination with 50 MUg/mL
      crude clove extracts. The effects of FMSP-nanoparticles alone and combined with
      clove extracts were observed after 24 hrs and 48 hrs intervals. The response of
      FMSP-nanoparticles-treated cells was evaluated by Trypan Blue, 4',6-diamidino-2
      phenylindole (DAPI), and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide (MTT) assays, respectively. We have demonstrated that cancer cell
      viability was decreased to 55.40% when treated with FMSP-nanoparticles alone,
      whereas when cancer cells were treated with FMSP-nanoparticles along with crude
      clove extracts, the cell viability was drastically decreased to 8.50%. Both
      morphological and quantitative data suggest that the combination of FMSP
      nanoparticles plus crude clove extracts are more effective in treating cancer
      cells and we suggest that the combination treatment of nanoparticles along with
      clove extracts hold a great promise for the cancer treatments.

PMID- 30210545
TI  - Prevalence of Multidrug-Resistant Escherichia coli Isolated from Drinking Water
      Sources.
AB  - The control of infectious diseases is badly endangered by the rise in the number
      of microorganisms that are resistant to antimicrobial agents. This is because
      infections caused by resistant microorganisms often fail to respond to
      conventional treatment, resulting in prolonged illness and greater risk of death.
      Antimicrobial-resistant bacteria are also present in various water sources. This
      study therefore sought to document the microbiological quality and antibiograms
      of bacterial isolates (E. coli strains) from six different water sources in order
      to determine their safety for human consumption and to provide updated antibiotic
      data for pragmatic treatment of patients. Bacteria isolation and identification
      was done using API and conventional methods. Antibiotic susceptibility testing
      was conducted using the Kirby-Bauer method. Results obtained indicated that all
      the water sources tested were of poor quality. Bacteria isolated included E.
      coli, Enterobacter spp., Klebsiella spp., Salmonella typhi, Streptococcus spp.,
      Proteus vulgaris, Vibrio cholera, Shigella spp., Pseudomonas aeruginosa, and
      Enterococcus faecalis. The prevalence of multidrug-resistant E. coli was 49.48%.
      E. coli isolates showed high resistance patterns to the tested antibiotics. They
      were most resistant to penicillin (32.99%), cefuroxime (28.87%), erythromycin
      (23.71%), and tetracycline (21.45%). In contrast, they were susceptible to
      nitrofurantoin (93.8%), cefotaxime and amikacin (91.75%), gentamicin (90.7%),
      nalidixic acid (89.65%), ciprofloxacin (74.2%), chloramphenicol (69.07%),
      pipemidic acid (65.97%), and cefuroxime (52.58%). Sixty-three percent (63%) of
      the multidrug-resistant E. coli strains recorded a multiple antibiotic resistance
      (MAR) index value >0.2. The susceptible antibiotics, especially the
      nitrofurantoin, are hence recommended in the practical treatment of waterborne
      bacterial diseases.

PMID- 30210546
TI  - Hearing Performance in the Follicular-Luteal Phase of the Menstrual Cycle.
AB  - Introduction: Estrogen has a protective role on auditory function. It may have an
      excitatory action on auditory nerve fibers and can have a neuroprotective effect.
      Progesterone has a mainly inhibitory action on the central nervous system, which
      may balance the mainly excitatory action of estrogen. Objective: To determine
      changes in hearing performance with pure tone audiometry (PTA), tympanometry,
      distortion product otoacoustic emissions (DPOAEs), and auditory brainstem
      responses (ABR) as hormonal changes occur from follicular to luteal phase.
      Materials and Methods: Twenty healthy female volunteers (age 19 +/- 30 years)
      with normal menstrual cycle and without any hearing problems are included in this
      case-control study. Hearing evaluation was performed on the 13th day of the
      menstrual cycle (follicular phase) and then on the 22nd day (luteal phase).
      Results: All of the participants had normal results in follicular phase. In
      luteal phase, four cases showed abnormalities as follows: reduced hearing
      thresholds 250 Hz (mean= 15 dBHL), increased amplitudes of DPOAE (mean= 3 dBspl),
      decreased middle ear pressure (mean= -110 dapa), and delayed ABR interpeak
      latencies (mean of IPLs I-III= 0.4 and mean of IPLs III-V= 0.6 ms). Conclusions:
      In some women, changing of ovarian hormones may induce fluctuating hearing and
      increased progesterone in luteal phase can lead to abnormal outcomes in auditory
      function. However, elevated estrogen modifies its consequences in follicular
      phase.

PMID- 30210547
TI  - Amniotic Epithelial Cells Accelerate Diabetic Wound Healing by Modulating
      Inflammation and Promoting Neovascularization.
AB  - Human amniotic epithelial cells (hAECs) are nontumorigenic, highly abundant, and
      low immunogenic and possess multipotent differentiation ability, which make them
      become ideal alternative stem cell source for regenerative medicine. Previous
      studies have demonstrated the therapeutic potential of hAECs in many tissue
      repairs. However, the therapeutic effect of hAECs on diabetic wound healing is
      still unknown. In this study, we injected hAECs intradermally around the full
      thickness excisional skin wounds of db/db mice and found that hAECs significantly
      accelerated diabetic wound healing and granulation tissue formation. To explore
      the underlying mechanisms, we measured inflammation and neovascularization in
      diabetic wounds. hAECs could modulate macrophage phenotype toward M2 macrophage,
      promote switch from proinflammatory status to prohealing status of wounds, and
      increase capillary density in diabetic wounds. Furthermore, we found that the
      hAEC-conditioned medium promoted macrophage polarization toward M2 phenotype and
      facilitated migration, proliferation, and tube formation of endothelial cells
      through in vitro experiments. Taken together, we first reported that hAECs could
      promote diabetic wound healing, at least partially, through paracrine effects to
      regulate inflammation and promote neovascularization.

PMID- 30210548
TI  - Comparative Analysis of Human Adipose-Derived Mesenchymal Stem Cells from Orbital
      and Abdominal Fat.
AB  - Adipose tissue contains abundant multipotent mesenchymal stem cells with strong
      proliferative and differentiating potential into adipocytes, osteocytes, and
      chondrocytes. However, adipose-derived mesenchymal stem cells (ASCs) showed
      variable characteristics based on the tissue-harvesting site. This study aimed at
      comparing human adipose-derived mesenchymal stem cell from the orbit (Orbital
      ASCs) and abdomen (Abdominal ASCs). Orbital and abdominal ASCs were isolated
      during an upper or lower blepharoplasty operation and liposuction, respectively.
      Flow cytometric analysis was done to analyze the surface antigens of ASCs, and
      cytokine profiles were measured using Luminex assay kit. The multilineage
      potential of both ASCs was investigated using Oil Red O, alizarin red, and alcian
      staining. Reverse transcriptase polymerase chain reaction (RT-PCR) was performed
      to measure mRNA levels of genes involved in these trilineage differentiations.
      Our results showed that both types of ASCs expressed the cell surface markers
      which are commonly expressed stem cells; however, orbital-ASCs showed higher
      expressions of CD73, CD90, CD105, and CD146 than abdominal ASCs. Unlikely,
      orbital-ASC expressed CD31, CD45 and HLA-DR lesser than abdominal-ASCs. Orbital
      ASCs secreted higher concentrations of eotaxin, fractalkine, IP-10, GRO, MCP-1,
      IL-6, IL-8, and RANTES but lower MIP-1alpha, FGF-2, and VEGF concentrations than
      abdominal-ASCs. Our result showed that orbital ASCs have higher potential towards
      adipogenic and osteogenic differentiation but lower tendency to chondrogenesis
      when compared with abdominal ASCs. In conclusion, tissue-harvesting site is a
      strong determinant for characterization of adipose-derived mesenchymal stem
      cells. Understanding defining phenotypes of such cells is useful for making
      suitable choices in different regenerative clinical indications.

PMID- 30210549
TI  - GM1 Ganglioside Promotes Osteogenic Differentiation of Human Tendon Stem Cells.
AB  - Gangliosides, the sialic acid-conjugated glycosphingolipids present in the lipid
      rafts, have been recognized as important regulators of cell proliferation,
      migration, and apoptosis. Due to their peculiar localization in the cell
      membrane, they modulate the activity of several key cell receptors, and
      increasing evidence supports their involvement also in stem cell differentiation.
      In this context, herein we report the role played by the ganglioside GM1 in the
      osteogenic differentiation of human tendon stem cells (hTSCs). In particular, we
      found an increase of GM1 levels during osteogenesis that is instrumental for
      driving the process. In fact, supplementation of the ganglioside in the medium
      significantly increased the osteogenic differentiation capability of hTSCs.
      Mechanistically, we found that GM1 supplementation caused a reduction in the
      phosphorylation of the platelet-derived growth factor receptor-beta (PDGFR-beta),
      which is a known inhibitor of osteogenic commitment. These results were further
      corroborated by the observation that GM1 supplementation was able to revert the
      inhibitory effects on osteogenesis when the process was inhibited with exogenous
      PDGF.

PMID- 30210550
TI  - Significance of Glioma Stem-Like Cells in the Tumor Periphery That Express High
      Levels of CD44 in Tumor Invasion, Early Progression, and Poor Prognosis in
      Glioblastoma.
AB  - Glioblastoma multiforme (GBM) is the most aggressive malignant brain tumor and a
      subpopulation of glioma stem-like cells (GSCs) is likely responsible for the
      invariable recurrence following maximum resection and chemoradiotherapy. As most
      GSCs that are located in the perivascular and perinecrotic niches should be
      removed during tumor resection, it is very important to know where surviving GSCs
      are localized. Here, we investigated the existence and functions of GSCs in the
      tumor periphery, which is considered to constitute the invasion niche for GSCs in
      GBM, by analyzing expression of stem cell markers and stem cell-related molecules
      and measuring particular activities of cultured GSCs. In addition, the
      relationship between GSCs expressing particular stem cell markers and
      pathological features on MRI and prognosis in GBM patients was analyzed. We
      showed that GSCs that express high levels of CD44 are present in the tumor
      periphery. We also found that vascular endothelial growth factor (VEGF) is
      characteristically expressed at a high level in the tumor periphery. Cultured
      GSCs obtained from the tumor periphery were highly invasive and have enhanced
      migration phenotype, both of which were markedly inhibited by CD44 knockdown.
      Higher expression of CD44 in the tumor periphery than in the core was correlated
      with a highly invasive feature on MRI and was associated with early tumor
      progression and worse survival, whereas lower expression of CD44 in the tumor
      periphery corresponded to low invasion and was associated with longer survival.
      The low invasion type on MRI tended to show high levels of VEGF expression in the
      tumor periphery, thus presenting the tumor with high proliferative activity.
      These results imply the significance of GSCs with high levels of CD44 expression
      in the tumor periphery compared to the core, not only in tumor invasion but also
      rapid tumor progression and short survival in patients with GBM.

PMID- 30210551
TI  - Noncoding RNA Transcripts during Differentiation of Induced Pluripotent Stem
      Cells into Hepatocytes.
AB  - Recent advances in the stem cell field allow to obtain many human tissues in
      vitro. However, hepatic differentiation of induced pluripotent stem cells (iPSCs)
      still remains challenging. Hepatocyte-like cells (HLCs) obtained after
      differentiation resemble more fetal liver hepatocytes. MicroRNAs (miRNA) play an
      important role in the differentiation process. Here, we analysed noncoding RNA
      profiles from the last stages of differentiation and compare them to hepatocytes.
      Our results show that HLCs maintain an epithelial character and express miRNA
      which can block hepatocyte maturation by inhibiting the epithelial-mesenchymal
      transition (EMT). Additionally, we identified differentially expressed small
      nucleolar RNAs (snoRNAs) and discovered novel noncoding RNA (ncRNA) genes.

PMID- 30210553
TI  - Circadian and Geotactic Behaviors: Genetic Pleiotropy in Drosophila Melanogaster.
AB  - Data presented in this paper test the hypotheses that Hirsch's positive geotaxis
      (Lo) and negative geotaxis (Hi5) strains of Drosophila melanogaster (fruit fly)
      differ in length of the free-running circadian activity period (tau) as well as
      adult geotaxis. Several genes have been shown to alter geotaxis in Drosophila.
      Two of these genes, cryptochrome (cry) and Pigment-dispersing-factor (Pdf) are
      integral to the function of biological clocks. Pdf plays a crucial role in
      maintaining free-running circadian periods. The cry gene alters blue-light (<420
      nm) phototransduction which affects biological clocks, spatial orientation and
      taxis relative to gravity, magnetic fields, solar, lunar, and celestial radiation
      in several species. The cry gene is involved in phase resetting (entrainment) of
      the circadian clock by blue light (<420 nm). Geotaxis involves spatial
      orientation, so it might be expected that geotaxis is linked genetically with
      other forms of spatial orientation. The association between geotaxis and
      biological clocks is less intuitive. The data and the literature presented here
      show that genes, physiology and behavioural aspects of geotaxis, biological
      clocks, magnetosensitivity and other types of spatial orientation, are complex,
      intriguing and interrelated.

PMID- 30210554
TI  - Effects of Cold-Dry (Harmattan) and Hot-Dry Seasons on Daily Rhythms of Rectal
      and Body Surface Temperatures in Sheep and Goats in a Natural Tropical
      Environment.
AB  - Studies on daily rhythmicity in livestock under natural conditions are limited,
      and there is mounting evidence that rhythm patterns differ between
      chronobiological studies conducted in the laboratory and studies conducted under
      pronounced natural seasonality. Here, we investigated the influence of cold-dry
      (harmattan) and hot-dry seasons on daily rhythmicity of rectal (RT) and body
      surface temperatures (BST) in indigenous sheep and goats under natural light-dark
      cycles. The RT and BST of the animals, and the ambient temperature (AT) and
      relative humidity (RH) inside the pen, were measured every three hours for a
      period of two days, twice on separate days during the hot-dry and the harmattan
      seasons, respectively. The AT and RH had minimum values of 16 degrees C and 15%
      recorded during the harmattan and maximum values of 32 degrees C and 46% recorded
      during the hot-dry season, respectively. A trigonometric statistical model was
      applied to characterize the main rhythmic parameters according to the single
      cosinor procedure. The result showed that RT and BST exhibited different degrees
      of daily rhythmicity, and their oscillatory patterns differed with the seasons
      (larger amplitude during the harmattan season than during the hot-dry season).
      The goats displayed greater (p < 0.05) amplitude of BST than the sheep in all
      seasons. The acrophases were restricted to the light phase of the light-dark
      cycle. The mesor of RT in goats was not affected by the season, but mesors of BST
      in both species were significantly higher (p < 0.05) during the hot-dry than the
      harmattan season. The goats had a more robust RT rhythm (70%) as compared to the
      sheep (56%). Overall, the results demonstrated that seasonal changes influenced
      considerably the daily rhythmicity of RT and BST in sheep and goats under natural
      light-dark cycle. Awareness of these changes may be useful in the improvement of
      diagnosis, treatment and prevention of diseases, and welfare and productivity of
      sheep and goats under cold-dry and hot-dry conditions.

PMID- 30210556
TI  - A Bibliometric Analysis of the Top 100 Most Cited Chronotype Research Papers.
AB  - Bibliometric indices are a widely used measure of research impact. The aim of the
      current study was to identify and characterise the top one hundred most-cited
      research articles in the topic of chronotype research. A search of the Thomson
      Reuters Web of Science database returned 974 eligible articles (published between
      1990 and 2016). Citations for the 100 most-cited articles ranged between 438 and
      29. The most represented journal was Chronobiology International (n = 30). Nearly
      50% of articles originated in Germany and the U.S. The bibliometrics reported
      identify key publications and provide insight into trends within the topic of
      chronotype research.

PMID- 30210555
TI  - Differences in Photic Entrainment of Circadian Locomotor Activity Between Lean
      and Obese Volcano Mice (Neotomodon alstoni).
AB  - Obesity is a growing problem worldwide with a clear impact on health status. It
      is also a condition that negatively affects circadian rhythms. When the mouse
      Neotomodon alstoni is fed a regular rodent chow, some individuals develop
      obesity, representing an opportunity to compare the effects of spontaneous
      obesity upon the circadian organization in this species with that observed in
      other rodents with induced obesity. We report differences in the free running
      circadian locomotor activity rhythm and in the effects of light pulses between
      lean and obese mice. Also, the photo-induced expression of the c-Fos protein and
      vasoactive intestinal peptide (VIP) in the suprachiasmatic nucleus (SCN) were
      examined at circadian time (CT) 14 and 22. We show that obese mice have a larger
      dispersion of the period of circadian locomotor rhythm in constant darkness.
      Photic induced phase shifts are nearly 50% shorter at CT 14, and 50% larger at CT
      22 than in lean mice. The photoinduction of VIP in the SCN at CT 22 was larger in
      obese mice, which may be related to the differences observed in photic phase
      shifting. Our work indicates that the obesity in Neotomodon has effects on the
      neural mechanisms that regulate the circadian system.

PMID- 30210552
TI  - Mesenchymal Stromal/Stem Cells in Regenerative Medicine and Tissue Engineering.
AB  - As a result of over five decades of investigation, mesenchymal stromal/stem cells
      (MSCs) have emerged as a versatile and frequently utilized cell source in the
      fields of regenerative medicine and tissue engineering. In this review, we
      summarize the history of MSC research from the initial discovery of their
      multipotency to the more recent recognition of their perivascular identity in
      vivo and their extraordinary capacity for immunomodulation and angiogenic
      signaling. As well, we discuss long-standing questions regarding their
      developmental origins and their capacity for differentiation toward a range of
      cell lineages. We also highlight important considerations and potential risks
      involved with their isolation, ex vivo expansion, and clinical use. Overall, this
      review aims to serve as an overview of the breadth of research that has
      demonstrated the utility of MSCs in a wide range of clinical contexts and
      continues to unravel the mechanisms by which these cells exert their therapeutic
      effects.

PMID- 30210558
TI  - Neurophysiological Processing of an Emotional Task is Sensitive to Time-of-Day.
AB  - Previous work from our laboratory has shown that a measure of attention to
      emotionally-charged stimuli, the late positive potential (LPP) event related
      potential (ERP), distinguished neutral from emotional pictures on a baseline day,
      but not after sleep deprivation. Here we sought to extend these findings and
      address the uncertainty about the effect of time-of-day on emotion processing by
      testing a morning group (8:00-10:00 a.m., n = 30) and an evening group (8:00
      10:00 p.m., n = 30). We also examined the extent of diurnal changes in cortisol
      related to the emotion processing task. Results from this study mirrored those
      found after one night of sleep deprivation. Compared to the morning group, the
      LPP generated by the evening group (who had a greater homeostatic sleep drive)
      did not distinguish neutral from emotionally-charged stimuli. New to this study,
      we also found that there was a time-of-day effect on positive, but not negative
      pictures. While, as expected, cortisol levels were higher in the morning relative
      to the evening group, there was no relationship between cortisol and the LPP ERP
      emotion measure. In addition, neither time-of-day preference nor sleep quality
      was related to the LPP measure. These findings show that, similar to what occurs
      after sleep deprivation, increased sleep pressure throughout the day interferes
      with attention processing to emotional stimuli.

PMID- 30210557
TI  - Differential Expression of Circadian Genes in Leukemia and a Possible Role for
      Sirt1 in Restoring the Circadian Clock in Chronic Myeloid Leukemia.
AB  - Disregulation of genes making up the mammalian circadian clock has been
      associated with different forms of cancer. This study aimed to address how the
      circadian clock genes behave over the course of treatment for both the acute and
      chronic forms of leukemia and whether any could be used as potential biomarkers
      as a read-out for therapeutic efficacy. Expression profiling for both core and
      ancillary clock genes revealed that the majority of clock genes are down
      regulated in acute myeloid leukemia patients, except for Cry2, which is up
      regulated towards the end of treatment. A similar process was seen in acute
      lymphocytic leukemia patients; however, here, Cry2 expression came back up
      towards control levels upon treatment completion. In addition, all of the core
      clock genes were down-regulated in both chronic forms of leukemia (chronic
      myeloid leukemia and chronic lymphocytic leukemia), except for Cry2, which was
      not affected when the disease was diagnosed. Furthermore, the NAD(+) - dependent
      protein deacetylase Sirt1 has been proposed to have a dual role in both control
      of circadian clock circuitry and promotion of cell survival by inhibiting
      apoptotic pathways in cancer. We used a pharmacological-based approach to see
      whether Sirt1 played a role in regulating the circadian clock circuitry in both
      acute and chronic forms of leukemia. Our results suggest that interfering with
      Sirt1 leads to a partial restoration of BMAL1 oscillation in chronic myeloid
      leukemia patient samples. Furthermore, interfering with Sirt1 activity led to
      both the induction and repression of circadian clock genes in both acute and
      chronic forms of leukemia, which makes it a potential therapeutic target to
      either augment existing therapies for chronic leukemia or to act as a means of
      facilitating chronotherapy in order to maximize both the effectiveness of
      existing therapies and to minimize therapy-associated toxicity.

PMID- 30210559
TI  - Daily Rhythms of Blood Parameters in Broiler Chickens Reared under Tropical
      Climate Conditions.
AB  - Several studies carried out on humans and other mammals show that the temporal
      organisation of haematological parameters in the blood exhibit daily rhythms;
      however, such studies have been rare in poultry reared under a natural
      photoperiod. The present study investigated the occurrence of daily rhythms in
      blood parameters of broiler chickens kept under tropical climatic conditions. Ten
      6-7-week-old broiler chickens served as subjects of the study. They were kept in
      standard individual cages under natural light-dark cycle and given access to feed
      and water ad libitum. Two milliliters of blood was collected from each bird via
      intravenous cannulae inserted into the wing vein. The blood samples were
      collected every 4 h over a 24-h period, starting from 09:00 h on the first day
      and completed at 09:00 h on the second day. The blood samples were analysed for
      erythrocyte, total and differential leucocyte counts. A trigonometric statistical
      model according to the single cosinor procedure was used to describe the periodic
      parameters and their acrophases, and ANOVA was used to determine significant
      differences. The results demonstrated the existence of daily rhythms in packed
      cell volume, haemoglobin, white blood cell, red blood cell, heterophil,
      lymphocyte, eosinophil and monocyte counts, while total protein displayed no
      rhythm. The characteristics of the haematological parameters showed that the
      acrophases were restricted to the light phase of the light/dark cycle, precisely
      at 09:00 h, except for eosinophil and heterophil counts, which had acrophases at
      21:00 h. The amplitudes of the blood parameters varied, with packed cell volume
      having the greatest amplitude of 4.2 +/- 0.5, closely followed by lymphocyte (3.4
      +/- 0.5) and heterophil (2.3 +/- 0.2) counts. In conclusion, the results of the
      study demonstrated the existence of daily rhythms with diurnal acrophases in
      blood parameters of broiler chickens kept under natural photoperiods and tropical
      conditions.

PMID- 30210560
TI  - DEC2 Blocks the Effect of the ARNTL2/NPAS2 Dimer on the Expression of PER3 and
      DBP.
AB  - The expression of clock genes ARNTL2, NPAS2 and DEC2 are disturbed in rheumatoid
      arthritis, an autoimmune disease with circadian variation of symptoms. We have
      shown that TNF is a potent inducer of these genes. We investigated the regulation
      of ARNTL2 and NPAS2 by TNF and elucidated their effect on other clock gene
      expressions. Additionally, we studied the effect of DEC1 and DEC2 on ARNTL,
      ARNTL2 and NPAS2. Cultured primary human fibroblasts were stimulated with TNF and
      the effects on ARNTL2 and NPAS2 were studied with RT-qPCR and immunofluorescence
      staining. The role of NF-kappaB was analyzed using IKK-2 inhibitor IMD-0354. TNF
      promoted ARNTL2 localization into the nuclei. Similar to DEC2, the effects of TNF
      on ARNTL2 and NPAS2 expressions were mediated via NF-kappaB. Cloned ARNTL,
      ARNTL2, NPAS2, DEC1 and DEC2 were transfected into HEK293. The ARNTL2/NPAS2 dimer
      was a weaker inducer of PER3 and DBP than ARNTL/NPAS2. ARNTL2 and NPAS2 are
      regulated by TNF via the same mechanism as DEC2. Compared to their paralogs they
      have unique effects on other circadian components. Our data suggest that these
      genes are responsible, at least in fibroblasts, for the accurate adaptation of
      circadian timekeeping in individual cells during inflammation.

PMID- 30210561
TI  - Comparison of Melatonin Profile and Alertness of Firefighters with Different Work
      Schedules.
AB  - Introduction: A two-shift work schedule with different rotations is common among
      firefighters in Iranian petrochemical companies. This study compared salivary
      melatonin and sleepiness on the last night before turning to day shift at 19:00,
      23:00, 3:00, and 7:00 among petrochemical firefighters (PFFs) working seven and
      four consecutive night shifts. Methods: Sixty four PFFs working in the
      petrochemical industry were selected. To measure melatonin, saliva samples were
      taken, whereas the KSS index was used to assess sleepiness. Chi-square and
      independent samples t-test were carried out to analyze the data, and generalized
      linear model (GLM) was employed to determine the effect of confounding factors
      such as lighting and caffeine. Results: The levels of melatonin at 3:00 and 7:00,
      and the overall changes during the shift in the two shift patterns under the
      study were different (P < 0.05). Sleepiness was significantly different only at
      3:00 in the two studied shift patterns, while the effects of lighting and
      caffeine on melatonin changes were not significant (P > 0.05). Conclusion: It
      seems that a slow shift rotation is better because it reduces the secretion of
      melatonin (hence reducing sleepiness during the night) and changes the peak of
      melatonin secretion to the daytime, which is a sign of adaptation.

PMID- 30210562
TI  - Seasonal Variation in Bright Daylight Exposure, Mood and Behavior among a Group
      of Office Workers in Sweden.
AB  - The purpose of the study was to investigate seasonal variation in mood and
      behavior among a group of office workers in Sweden (56 degrees N). Thirty
      subjects participated in this longitudinal study. The subjects kept a weekly log
      that included questionnaires for ratings of psychological wellbeing and daily
      sleep-activity diaries where they also noted time spent outdoors. The lighting
      conditions in the offices were subjectively evaluated during one day, five times
      over the year. There was a seasonal variation in positive affect and in sleep
      activity behavior. Across the year, there was a large variation in the total time
      spent outdoors in daylight. The subjects reported seasonal variation concerning
      the pleasantness, variation and strength of the light in the offices and
      regarding the visibility in the rooms. Finally, the subjects spent most of their
      time indoors, relying on artificial lighting, which demonstrates the importance
      of the lighting quality in indoor environments.

PMID- 30210563
TI  - Relationship Between the Cortisol-Estradiol Phase Difference and Affect in Women.
AB  - Affective disorders impact women's health, with a lifetime prevalence of over
      twelve per cent. They have been correlated with reproductive cycle factors, under
      the regulation of hormonal circadian rhythms. In affective disorders, circadian
      rhythms may become desynchronized. The circadian rhythms of cortisol and
      estradiol may play a role in affective disorders. The purpose of this study was
      to explore the temporal relationship between the rhythms of cortisol and
      estradiol and its relationship to affect. It was hypothesized that a cortisol
      estradiol phase difference (PD) exists that correlates with optimal affect. A
      small scale, comparative, correlational design was used to test the hypothesis.
      Twenty-three women were recruited from an urban university. Salivary samples were
      collected over a twenty-four-hour period and fitted to a cosinor model.
      Subjective measures of affect were collected. Relationships between the cortisol
      estradiol PD and affect were evaluated using a second-degree polynomial equation.
      Results demonstrated a significant correlation in affect measures (p < 0.05). An
      optimal PD was identified for affect to be 3.6 hours. The phase relationship
      between cortisol and estradiol may play a role in the development of alterations
      in affective disorders.

PMID- 30210564
TI  - Are Type 2 Diabetes Mellitus and Depression Part of a Common Clock Genes Network?
AB  - In recent years, there has been an increased prevalence of type 2 diabetes
      mellitus (T2DM) and depression across the world. This growing public health
      problem has produced an increasing socioeconomic burden to the populations of all
      affected countries. Despite an awareness by public health officials and medical
      researchers of the costs associated with these diseases, there still remain many
      aspects of how they develop that are not understood. In this article, we propose
      that the circadian clock could be a factor that coordinates both the
      neurobehavioral and metabolic processes that underlie depression and T2DM. We
      propose further that this perspective, one which emphasizes the regulatory
      effects of clock gene activity, may provide insights into how T2DM and depression
      interact with one another, and may thus open a new pathway for managing and
      treating these disorders.

PMID- 30210565
TI  - Time of Administration of Acute or Chronic Doses of Imipramine Affects its
      Antidepressant Action in Rats.
AB  - The pathogenesis and therapeutics of depression are linked to the operation of
      the circadian system. Here, we studied the chronopharmacological action of a
      tricyclic antidepressant, imipramine. Male adult Wistar-Hannover rats were
      administered imipramine acutely or chronically in the morning or in the evening.
      The antidepressant action of imipramine was analyzed using the forced swim test
      (FST). A single dose of imipramine (30 mg/kg) in the morning, but not in the
      evening, reduced immobility and increased climbing in the FST. The plasma
      concentrations of imipramine and its metabolite, desipramine, were slightly
      higher in the morning than in the evening, which might explain the dosing time
      dependent action of imipramine. Next, we analyzed the effect of chronic
      imipramine treatment. Rats received imipramine in the morning or in the evening
      for 2 weeks. The morning treatment resulted in larger effects in the FST than the
      evening treatment, and was effective at a dose that was ineffective when
      administered acutely. The levels of brain alpha-adrenergic receptors tended to
      decrease after chronic imipramine treatment. Imipramine might interact with
      noradrenergic neurons, and this interaction might chronically alter receptor
      expression. This alteration seemed greater in the morning than in the evening,
      which might explain the dosing time-dependent action of imipramine.

PMID- 30210566
TI  - P19 Cells as a Model for Studying the Circadian Clock in Stem Cells before and
      after Cell Differentiation.
AB  - In mammals, circadian rhythmicity is sustained via a
      transcriptional/translational feedback loop referred to as the canonical
      molecular circadian clock. Circadian rhythm is absent in undifferentiated
      embryonic stem cells; it begins only after differentiation. We used pluripotent
      P19 embryonal carcinoma stem cells to check the biological clock before and after
      differentiation into neurons using retinoic acid. We show that the central clock
      genes ARNTL (Bmal), Per2 and Per3, and the peripheral clock genes Rev-erb-alpha
      and ROR-alpha, oscillate before and after differentiation, as does the expression
      of the neuronal differentiation markers Hes5, beta-3-tubulin (Tubb3) and Stra13,
      but not Neurod1. Furthermore, the known clock-modulating compounds ERK, EGFR,
      Pi3K, p38, DNA methylation and Sirtiun inhibitors, in addition to Rev-erb-alpha
      ligands, modulate the expression of central and peripheral clock genes.
      Interestingly Sirtinol, Sirt1 and Sirt2 inhibitors had the greatest significant
      effect on the expression of clock genes, and increased Hes5 and Tubb3 expression
      during neuronal differentiation. Our findings reveal a new frontier of circadian
      clock research in stem cells: contrary to what has been published previously, we
      have shown the clock to be functional and to oscillate, even in undifferentiated
      stem cells. Modulating the expression of clock genes using small molecules could
      affect stem cell differentiation.

PMID- 30210569
TI  - Corrigendum to "The Effect of Sanggua Drink Extract on Insulin Resistance through
      the PI3K/AKT Signaling Pathway".
AB  - [This corrects the article DOI: 10.1155/2018/9407945.].

PMID- 30210567
TI  - Circadian Rhythms, Exercise, and Cardiovascular Health.
AB  - Human circadian rhythmicity is driven by a circadian clock comprised of two
      distinct components: the central clock, located in the suprachiasmatic nucleus
      (SCN) within the hypothalamus, and the peripheral clocks, located in almost all
      tissues and organ systems in the body. Entrainment, or alignment, of circadian
      rhythmicity is dependent upon time of day and can occur through environmental
      influences such as light cues and physical activity exerted on skeletal muscle.
      Entrainment of the circadian clock through exercise has been reported to improve
      health by reducing risk of conditions such as cardiovascular disease (CVD), but
      further research is still needed. The purpose of this review is to discuss the
      effects exercise has on the regulation of circadian rhythmicity, specifically
      with respect to CVD risk factors - including hormonal levels, sleep/wake cycles,
      blood pressure, and heart rate. Additionally, the impact of exercise-induced
      circadian entrainment is discussed relative to hormone regulation, nocturnal
      blood pressure dipping, post-exercise hypotension, and overall cardiovascular
      health.

PMID- 30210568
TI  - Circadian Effects on Performance and Effort in Collegiate Swimmers.
AB  - Although individual athletic performance generally tends to peak in the evening,
      individuals who exhibit a strong diurnal preference perform better closer to
      their circadian peak. Time-of-day performance effects are influenced by circadian
      phenotype (diurnal preference and chronotype-sleep-wake patterns), homeostatic
      energy reserves and, potentially, genotype, yet little is known about how these
      factors influence physiological effort. Here, we investigate the effects of time
      of day, diurnal preference, chronotype, and PER3 (a circadian clock gene)
      genotype on both effort and performance in a population of Division I collegiate
      swimmers (n = 27). Participants competed in 200m time trials at 7:00 and 19:00
      and were sampled pre- and post-trial for salivary alpha-amylase levels (as a
      measure of physiological effort), allowing for per-individual measures of
      performance and physiological effort. Hair samples were collected for genotype
      analysis (a variable-number tandem-repeat (VNTR) and a single nucleotide
      polymorphism (SNP) in PER3). Our results indicate significant and parallel time
      of-day by circadian phenotype effects on swim performance and effort; evening
      type swimmers swam on average 6% slower with 50% greater alpha-amylase levels in
      the morning than they did in the evening, and morning types required 5-7 times
      more effort in the evening trial to achieve the same performance result as the
      morning trial. In addition, our results suggest that these performance effects
      may be influenced by gene (circadian clock gene PER3 variants) by environment
      (time of day) interactions. Participants homozygous for the PER34,4 length
      variant (rs57875989) or who possess a single G-allele at PER3 SNP rs228697 swam 3
      6% slower in the morning. Overall, these results suggest that intra-individual
      variation in athletic performance and effort with time of day is associated with
      circadian phenotype and PER3 genotype.

PMID- 30210570
TI  - Erzhi Formula Extracts Reverse Renal Injury in Diabetic Nephropathy Rats by
      Protecting the Renal Podocytes.
AB  - Podocytes injury was a crucial factor resulting in diabetic nephropathy (DN).
      Erzhi formula extract (EZF) was a clinical effective Chinese medicine on DN, but
      its mechanism was unclear. In this study, the main compounds of EZF and their
      pharmacokinetics in rat were detected by HPLC-MS/MS. And then, blood glucose,
      urine protein, renal index, renal microstructural (HE/PAS staining), inflammatory
      factors (IL-beta, TNF-alpha, IL-6), and protein/mRNA expression related to the
      function of podocyte (CD2AP and Podocin) in DN rats were investigated after the
      oral administration of EZF. The concentrations of specnuezhenide and
      wedelolactone in rat kidney were 7.19 and 0.057 mg/kg, respectively. The Tmax of
      specnuezhenide and wedelolactone were 2.0 and 1.50 h, respectively. Their Cmax
      were, respectively, 30.24 +/- 2.68 and 6.39 +/- 0.05 MUg/L. Their AUC(0-infinity)
      were 123.30 +/- 2.68 and 16.56 +/- 0.98 MUg/L*h, respectively. Compared with the
      model group, the blood glucose and the 24-hour urinary protein were significantly
      decreased (P < 0.05) after 16 weeks' treatment of EZF. The expressions of Podocin
      and CD2AP protein/mRNA were increased (P < 0. 05). The deteriorate of glomerular
      morphology was alleviated under the treatment of EZF. EZF prominently decreased
      the levels of inflammatory factors (P < 0.05). MDA was significantly decreased (P
      < 0.05) with the significant increase of SOD activity (P < 0.05) in EZF groups.
      All the results proved that EZF repaired glomerular mesangial matrix, protected
      renal tubule, and improved renal function in DN rats by upregulating the
      expression of Podocin and CD2AP protein/mRNA in podocytes.

PMID- 30210571
TI  - Therapeutic Efficacies of Artemisia capillaris Extract Cream Formulation in
      Imiquimod-Induced Psoriasis Models.
AB  - A cream formulation containing Artemisia capillaris (AC) extract (ACE) was
      developed for psoriasis therapy. Although ACE can be dissolved in organic
      solvents, its topical application is restricted because of toxicities. Therefore,
      a cream formulation was developed for the convenient and safe local application
      of ACE on skin lesions. The antipsoriatic properties of the ACE cream were
      evaluated using an imiquimod- (IMQ-) induced psoriasis-like mouse model. In
      psoriasis-like mouse models, the cumulative score (redness, thickness, and
      scaling) of the IMQ + ACE cream group was significantly lower than those of the
      other groups on day 4 (p < 0.05). The results of the hematoxylin and eosin
      staining of skin tissues revealed that the epidermal thickness value of the IMQ +
      ACE cream group was significantly lower than those of the other experimental
      groups (p < 0.05). The expression level of intracellular adhesion molecule-1
      (ICAM-1), which indicates the leukocyte infiltration into the skin and subsequent
      interactions with keratinocytes, was also lower in the IMQ + ACE cream group than
      in the IMQ group. These results indicate that ACE cream formulation could be used
      safely and conveniently for psoriasis treatment.

PMID- 30210572
TI  - Synergistic Effect of Bupleuri Radix and Scutellariae Radix on Adipogenesis and
      AMP-Activated Protein Kinase: A Network Pharmacological Approach.
AB  - Obesity has become a major health threat in developed countries. However, current
      medications for obesity are limited because of their adverse effects. Interest in
      natural products for the treatment of obesity is thus rapidly growing. Korean
      medicine is characterized by the wide use of herbal formulas. However, the
      combination rule of herbal formulas in Korean medicine lacks experimental
      evidence. According to Shennong's Classic of Materia Medica, the earliest book of
      herbal medicine, Bupleuri Radix (BR) and Scutellariae Radix (SR) possess the
      Sangsoo relationship, which means they have synergistic features when used
      together. Therefore these two are frequently used together in prescriptions such
      as Sosiho-Tang. In this study, we used the network pharmacological method to
      predict the interaction between these two herbs and then investigated the effects
      of BR, SR, and their combination on obesity in 3T3-L1 adipocytes. BR, SR, and BR
      SR mixture significantly decreased lipid accumulation and the expressions of two
      major adipogenic factors, peroxisome proliferator-activated receptor-gamma
      (PPARgamma) and CCAAT/enhancer-binding protein-alpha (C/EBPalpha), and their
      downstream genes, Adipoq, aP2, and Lipin1 in 3T3-L1 cells. In addition, the BR-SR
      mixture had synergistic effects compared with BR or SR on inhibition of
      adipogenic-gene expressions. BR and SR also inhibited the protein expressions of
      PPARgamma and C/EBPalpha. Furthermore, the two extracts successfully activated
      AMP-activated protein kinase alpha (AMPK alpha), the key regulator of energy
      metabolism. When compared to those of BR or SR, the BR-SR mixture showed higher
      inhibition rates of PPARgamma and C/EBPalpha, along with higher activation rate
      of AMPK. These results indicate a new potential antiobese pharmacotherapy and
      also provide scientific evidence supporting the usage of herbal combinations
      instead of mixtures in Korean medicine.

PMID- 30210575
TI  - MAKING PUNISHMENT PAY: The Political Economy of Revenue, Race and Regime in the
      California Prison Boom.
AB  - Sociologists have neglected the politically channeled and racially connected role
      of leveraged debt in mass incarceration. We use qualitative and quantitative data
      from California, circa 1960-2000, to assess how Republican entrepreneurial
      leveraging of debt overcame contradictions between parochial preferences for
      punishment and resistance to paying taxes for building prisons. The leveraging of
      bond debt deferred and externalized the costs of building prisons, while
      repurposed lease revenue bonds massively enlarged and extended this debt and
      dispensed with the requirement for direct voter approval. A Republican-dominated
      punishment regime capitalized debt to build prisons in selected exurban
      Republican California counties with growing visible minority populations. We
      demonstrate that the innovative use of lease revenue bonds was the essential
      element that enlarged and extended funding of California prison construction by
      an order of magnitude that made this expansion a boom. With what Robert Merton
      called the consequences of imperious interest, this prison expansion enabled the
      imprisonment of an inordinately large and racially disproportionate inmate
      population.

PMID- 30210573
TI  - The Combination of Ephedrae herba and Coicis semen in Gambihwan Attenuates
      Obesity and Metabolic Syndrome in High-Fat Diet-Induced Obese Mice.
AB  - Gambihwan is a herbal prescription used in Korean medicine to treat obesity. The
      authors evaluated the effects and mechanisms of two types of Gambihwan (GBH1 and
      2) administered to high-fat diet- (HFD-) induced obese mice. Four-week-old
      C57BL/6 mice were fed a HFD for 8 weeks with or without GBH1 or 2 (100-200
      mg/kg/day by oral gavage). All mice were subjected to glucose tolerance testing
      after the 8-week treatment period and then euthanized. Serum insulin, lipids, and
      inflammatory cytokine levels were analyzed using commercial kits. Hepatic enzyme
      levels and lipid profiles were also investigated. Liver section slides were
      stained with Oil Red O (ORO) or hematoxylin and eosin (H&E) to assess lipid
      accumulation. GBH1 and 2 both significantly decreased body, liver, or adipose
      tissue weights in HFD-fed mice and significantly improved glucose tolerance
      (p<0.05 in all groups). Cholesterol levels in both sera and liver homogenates
      were significantly decreased by GBH1 and 2 (p<0.05 in all groups). In addition,
      serum inflammatory cytokines (p<0.05 in 200 mg/kg/day groups) and hepatic enzyme
      levels were significantly diminished by GBH administration at 200mg/kg/day
      (p<0.05 in all groups). Furthermore, histologic analyses of liver sections
      revealed GBH suppressed lipid accumulation. Both GBH types suppressed HFD-induced
      increases in body weight and obesity-related markers in HFD-fed mice despite the
      difference in constituents between GBH1 and 2. It is strongly assumed that the
      combination of Ephedrae herba and Coicis semen exerted the antiobesity effect.
      The results obtained show that the antiobesity effects of GBH warrant further
      investigation.

PMID- 30210574
TI  - Organic Extract of Justicia pectoralis Jacq. Leaf Inhibits Interferon-gamma
      Secretion and Has Bacteriostatic Activity against Acinetobacter baumannii and
      Klebsiella pneumoniae.
AB  - Justicia pectoralis Jacq. (Acanthaceae) leaves currently found in the Brazilian
      north-east are widely used to treat diabetes, menstrual pains, asthma, and other
      disorders. This work aimed to identify the phytochemical characterization and
      biological activities of J. pectoralis leaf extracts. The plant material was
      ground and the crude extracts were obtained with water or acetone: water (7:3
      v/v), yielding aqueous (JPA), and organic (JPO) extracts. Phytochemical
      characterization was performed by thin-layer chromatography (TLC) and high
      performance liquid chromatography (HPLC). Cytotoxicity was assessed by 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) assay and trypan
      blue (TB) exclusion assay in peripheral blood mononuclear cells (PBMCs), BALB/c
      splenocytes, and neoplastic cells (TOLEDO, K562, DU-145, and PANC-1) at 1, 10,
      and 100 MUg/mL. Antibacterial activity was evaluated using the microdilution test
      to obtain the minimum inhibitory concentration (MIC) and minimum bactericidal
      concentration (MBC). Cytokines, IFN-gamma, and IL-17A from culture supernatants
      of BALB/c mice splenocytes were measured by sandwich ELISA. In the TLC analysis,
      both JPA and JPO extracts presented coumarin and flavonoids. In addition, HPLC
      was able to identify coumarin, apigenin, and ellagic acid in both extracts. JPO
      IC50 was 57.59 +/- 1.03 MUg/mL (MTT) and 69.44 +/- 8.08 MUg/mL (TB) in TOLEDO.
      MIC value of JPO against Acinetobacter baumannii and Klebsiella pneumoniae was
      500 MUg/mL. JPO (100 MUg/mL) significantly inhibited IFN-gamma levels (p=0.03).
      J. pectoralis is a potential candidate to be further investigated as an IFN-gamma
      inhibitory agent and against Acinetobacter baumannii and Klebsiella pneumoniae.

PMID- 30210576
TI  - Biomechanical Responses of Neonatal Brachial Plexus to Mechanical Stretch.
AB  - This study investigated the biomechanical responses of neonatal piglet brachial
      plexus (BP) segments-root/trunk, chord, and nerve at two different rates, 0.01
      mm/second (quasistatic) and 10 mm/second (dynamic)-and compared their response to
      another peripheral nerve (tibial). Comparisons of mechanical responses at two
      different rates reported a significantly higher maximum load, maximum stress, and
      Young's modulus (E) values when subjected to dynamic rate. Among various BP
      segments, maximum stress was significantly higher in the nerve segments, followed
      by chord and then the root/trunk segments except no differences between chord and
      root/trunk segments at quasistatic rate. E values exhibited similar behavior
      except no differences between the chord and root/trunk segments at both rates and
      no differences between chord and nerve segments at quasistatic rate. No
      differences were observed in the strain values. When compared with the tibial
      nerve, only mechanical properties of BP nerves were similar to the tibial nerve.
      Mechanical stresses and E values reported in BP root/trunk and chord segments
      were significantly lower than tibial nerve at both rates. When comparing the
      failure pattern, at quasistatic rate, necking was observed at maximum load,
      before a complete rupture occurred. At dynamic rate, partial rupture at maximum
      load, followed by a full rupture, was observed. Occurrence of the rate-dependent
      failure phenomenon was highest in the root/trunk segments followed by chord and
      nerve segments. Differences in the maximum stress, E values, and failure pattern
      of BP segments confirm variability in their anatomical structure and warrant
      future histological studies to better understand their stretch responses.

PMID- 30210577
TI  - Anti-proliferative Effect of C3 Exoenzyme in Fibroblasts is Mediated by c-Jun
      Phosphorylation.
AB  - The ADP-ribosyltransferase C3 exoenzyme from C. botulinum selectively inactivates
      Rho and is therefore often used as an inhibitor for investigations on Rho
      signaling. Previous studies of our group revealed that C3 inhibited cell
      proliferation in HT22 cells accompanied by increased transcriptional activities
      of Sp1 and c-Jun and reduced levels of cyclin D1, p21 and phosphorylated p38. By
      use of a p38alpha-deficient and a p38alpha-expressing control cell line, the
      impact of p38 on C3-mediated inhibition of cell proliferation and alterations on
      MAPK signaling was studied by growth kinetic experiments and Western blot
      analyses. The cell growth of p38alpha-expressing cells was impaired by C3, while
      the p38alpha-deficient cells did not exhibit any C3-induced effect. The activity
      of the MKK3/6-p38 MAPK signaling cascade as well as the phosphorylation of c-Jun
      and JNK was reduced by C3 exclusively in the presence of p38alpha. Moreover, the
      activity of upstream MAPKKK TAK1 was lowered in the p38alpha-expressing cells.
      These results indicated a resistance of p38alpha-deficient cells to C3-mediated
      inhibition of cell growth. This anti-proliferative effect was highly associated
      with the decreased activity of c-Jun and upstream p38 and JNK MAPK signaling as a
      consequence of the absence of p38alpha in these cells.

PMID- 30210579
TI  - Transcriptional and Post-Translational Targeting of Myocyte Stress Protein 1
      (MS1) by the JNK Pathway in Cardiac Myocytes.
AB  - Myocyte Stress Protein 1 (MS1) is a muscle-specific, stress-responsive, regulator
      of gene expression. It was originally identified in embryonic mouse heart which
      showed increased expression in a rat model of left ventricular hypertrophy. To
      determine if MS1 was responsive to other stresses relevant to cardiac myocyte
      function, we tested if it could be induced by the metabolic stresses associated
      with ischaemia/reperfusion injury in cardiac myocytes. We found that metabolic
      stress increased MS1 expression, both at the mRNA and protein level, concurrent
      with activation of the c-Jun N-terminal Kinase (JNK) signalling pathway. MS1
      induction by metabolic stress was blocked by both the transcription inhibitor
      actinomycin D and a JNK inhibitor, suggesting that activation of the JNK pathway
      during metabolic stress in cardiac myocytes leads to transcriptional induction of
      MS1. MS1 was also found to be an efficient JNK substrate in vitro, with a major
      JNK phosphorylation site identified at Thr-62. In addition, MS1 was found to co
      precipitate with JNK, and inspection of the amino acid sequence upstream of the
      phosphorylation site, at Thr-62, revealed a putative Mitogen-Activated Protein
      Kinase (MAPK) binding site. Taken together, these data identify MS1 as a likely
      transcriptional and post-translational target for the JNK pathway in cardiac
      myocytes subjected to metabolic stress.

PMID- 30210578
TI  - Insights into the Shc Family of Adaptor Proteins.
AB  - The Shc family of adaptor proteins is a group of proteins that lacks intrinsic
      enzymatic activity. Instead, Shc proteins possess various domains that allow them
      to recruit different signalling molecules. Shc proteins help to transduce an
      extracellular signal into an intracellular signal, which is then translated into
      a biological response. The Shc family of adaptor proteins share the same
      structural topography, CH2-PTB-CH1-SH2, which is more than an isoform of Shc
      family proteins; this structure, which includes multiple domains, allows for the
      posttranslational modification of Shc proteins and increases the functional
      diversity of Shc proteins. The deregulation of Shc proteins has been linked to
      different disease conditions, including cancer and Alzheimer's, which indicates
      their key roles in cellular functions. Accordingly, a question might arise as to
      whether Shc proteins could be targeted therapeutically to correct their
      disturbance. To answer this question, thorough knowledge must be acquired;
      herein, we aim to shed light on the Shc family of adaptor proteins to understand
      their intracellular role in normal and disease states, which later might be
      applied to connote mechanisms to reverse the disease state.

PMID- 30210580
TI  - ER Stress Activates the TOR Pathway through Atf6.
AB  - Cellular signaling pathways are often interconnected. They accurately and
      efficiently regulate essential cell functions such as protein synthesis, cell
      growth, and survival. The target of rapamycin (TOR) signaling pathway and the
      endoplasmic reticulum (ER) stress response pathway regulate similar cellular
      processes. However, the crosstalk between them has not been appreciated until
      recently and the detailed mechanisms remain unclear. Here, we show that ER stress
      inducing drugs activate the TOR signaling pathway in S2R+ Drosophila cells.
      Activating transcription factor 6 (Atf6), a major stress-responsive ER
      transmembrane protein, is responsible for ER stress-induced TOR activation.
      Supporting the finding, we further show that knocking down of both site-1/2
      proteases (S1P/S2P), Atf6 processing enzymes, are necessary to connect the two
      pathways.

PMID- 30210581
TI  - An adapted imaginal exposure approach to traditional methods used within trauma
      focused cognitive behavioural therapy, trialled with a veteran population.
AB  - Trauma-focused cognitive behavioural therapy (TF-CBT) is beneficial for
      individuals with post-traumatic stress disorder (PTSD); however, a subset of
      clients struggle to engage with traditional methods, due to high levels of
      avoidance and dissociation. This paper aims to describe an adapted approach to
      imaginal reliving and prolonged exposure, to facilitate subsequent cognitive
      updating. The paper demonstrates the technique with veterans, who are a client
      group that may struggle with some aspects of traditionally implemented TF-CBT.
      Two case studies are described, both with PTSD symptoms stemming from traumatic
      military experiences. An adapted exposure technique is utilized to address the
      barriers of high dissociation, poor access to trauma-related cognitions and fixed
      intrusive imagery. The approach involved three stages: (1) reliving the trauma
      outdoors, (2) manipulating the perspectives of the imagery, and (3) restructuring
      the narrative with new perspectives. Both clients showed decreased dissociation
      and improved toleration of their traumatic imagery. Improvement of PTSD symptoms
      and quality-of-life functioning was observed for both clients on objective
      measures. Adapting TF-CBT to have a stronger emphasis on grounding and
      allocentric processing may be helpful for a subset of patients with PTSD that
      present with high levels of dissociation and avoidance. Further research and
      investigation into alternative populations is needed.

PMID- 30210583
TI  - The role of secukinumab in the treatment of psoriatic arthritis and ankylosing
      spondylitis.
AB  - Psoriatic arthritis and ankylosing spondylitis are chronic inflammatory diseases
      that can cause significant disability. The commercialization of the first tumour
      necrosis factor (TNF) inhibitors led to a radical improvement of the quality of
      life of people affected by these conditions; however, response was not universal,
      highlighting the need for alternative therapeutic targets. Secukinumab is a
      monoclonal interleukin (IL)-17A inhibitor which has been proven efficacious for
      psoriatic arthritis and ankylosing spondylitis in recent clinical trials.
      Dactylitis, enthesitis, skin and nails are some of the domains in which the
      inhibition of IL-17 has shown significant improvements apart from the joints. Its
      safety profile and satisfactory medium- to long-term outcome data are some of the
      aspects suggesting its potential impact in treatment protocols in the short term.

PMID- 30210582
TI  - Comparable efficacy and safety of dimethyl fumarate and teriflunomide treatment
      in Relapsing-Remitting Multiple Sclerosis: an Italian real-word multicenter
      experience.
AB  - Background: The aim of the study was to evaluate the achievement of 'no evidence
      of disease activity' (NEDA) over a 12-month period in a large multicenter
      population with relapsing remitting multiple sclerosis (RRMS) treated with
      delayed-release dimethyl fumarate (DMF) and teriflunomide (TRF) using a
      propensity-score adjustment. Methods: A time-to-event method was used to
      determine the percentages of patients with RRMS (pwRRMS) in both groups achieving
      NEDA 3 (no relapses, no 12-week confirmed disability progression, and no new
      T2/gadolinium-enhancing brain lesions). We described the safety profile of the
      investigated drugs. Results: Of the 587 pwRRMS treated with DMF and the 316
      pwRRMS treated with TRF, 468 pwRRMS were successfully paired by propensity score:
      234 on DMF and 234 on TRF. The percentages of pwRRMS who achieved NEDA 3 were
      80.3% in the DMF group and 77.2% in the TRF group. Serious adverse events
      occurred in four (1.9%) pwRRMS on DMF and in three (1.3%) pwRRMS on TRF.
      Conclusions: DMF and TRF significantly impacted RRMS disease activity in our
      study. Serious safety concerns were recorded in less than 2% of the studied
      population.

PMID- 30210585
TI  - Erratum: Protective effect of astragalosides from Radix Astragali on adriamycin
      induced podocyte injury.
AB  - [This corrects the article DOI: 10.3892/etm.2018.5933.].

PMID- 30210584
TI  - The role of golimumab in inflammatory arthritis. A review of the evidence.
AB  - Background: Golimumab (GOL) is a tumor necrosis factor inhibitor that is used for
      various types of inflammatory arthritis such as rheumatoid arthritis (RA),
      psoriatic arthritis (PsA), and ankylosing spondylitis (AS). This article is a
      systematic review of the evidence for the efficacy and safety of golimumab in
      inflammatory arthritides, specifically RA, PsA and AS. Methods: We conducted a
      search of randomized controlled trails in MEDLINE [PubMed], CENTRAL, Embase, and
      Current Controlled Trials databases (ClinicalTrials.gov) through 2017 for studies
      that evaluated golimumab in inflammatory arthritides. We focused on pivotal,
      phase III trials for this review of the safety and efficacy of the drug. However,
      as some important information is not available in detail in publications from the
      phase III studies, additional individual studies pertaining to antidrug
      antibodies were also included. Results: A total of 12, randomized, double-blind,
      placebo-controlled studies were included in this review of literature. Two trials
      focused on the GOL response in the PsA population, four trials focused on the GOL
      response in the AS population, and five trials focused on the GOL response in the
      RA population. Additional studies that evaluated autodrug antibodies produced in
      patients using GOL were also included. Conclusion: Golimumab was found to be
      clinically effective and also have a good safety profile in the treatment of RA,
      PsA, and AS based on data available from large studies.

PMID- 30210586
TI  - Exome sequencing reveals a novel MFN2 missense mutation in a Chinese family with
      Charcot-Marie-Tooth type 2A.
AB  - Charcot-Marie-Tooth (CMT) is a group of inherited peripheral neuropathies. To
      date, mutations in >80 genes are reportedly associated with CMT. Protein
      mitofusin 2 encoded by MFN2 serves an essential role in mitochondrial fusion and
      regulation of apoptosis, which has previously been reported to be highly
      associated with an axonal form of neuropathy (CMT2A). In the present study, a
      large Chinese family with severe CMT was reported and a genetic analysis of the
      disease was performed. A detailed physical examination for CMT was performed in
      13 family members and electrophysiological examinations were performed in 3
      affected family members. Whole-exome sequencing was performed on the proband, and
      the suspected variants were identified by Sanger sequencing. The pathogenicity of
      mutation was verified by restriction fragment length polymorphism analysis in the
      family followed by a bioinformatics analysis. A novel c.1190G>C; p.(R397P)
      mutation in the MFN2 gene was identified in the proband, and co-segregated
      between genotype and phenotype in the family. The substituted amino acid changed
      the hydrophobicity and charge characteristics of the mitofusin 2 coiled-coiled
      domain; thus it may affect its biological function. In summary, a novel
      pathogenic mutation was identified in a Chinese family with CMT, which expands
      the phenotypic and mutational spectrum of CMT2A, and provides evidence for
      prenatal interventions and more precise pharmacological treatments to this
      family.

PMID- 30210588
TI  - Salidroside prevents hydroperoxide-induced oxidative stress and apoptosis in
      retinal pigment epithelium cells.
AB  - Salidroside (SAL) is the major pharmacologically active constituent of Rhodiola
      rosea, which possesses a wide range of pharmacological functions, including anti
      aging, anti-inflammatory, antioxidant, anticancer and neuroprotective activities.
      However, the effects and mechanisms of SAL on oxidative stress in retinal pigment
      epithelial (RPE) cells exposed to hydrogen peroxide (H2O2) remain unclear. The
      present study investigated the protective effects of SAL and the underlying
      mechanisms against H2O2-induced oxidative stress in human RPE cells. ARPE-19
      cells were treated with various doses of SAL for 24 h and then exposed to 200 uM
      H2O2 for 24 h. Cell viability was analyzed by a MTT assay, and the intracellular
      levels of reactive oxygen species were measured using CellROX orange reagent.
      Cell apoptosis was analyzed by annexin V/propidium iodide double staining,
      followed by flow cytometry. The levels of B-cell lymphoma 2 (Bcl-2), Bcl-2
      associated X protein, phospho (p)-protein kinase B (Akt), Akt, p-glycogen
      synthase kinase (GSK)-3beta and GSK-3beta were evaluated using western blotting.
      The results demonstrated that SAL markedly attenuated H2O2-induced loss of cell
      viability. SAL also ameliorated H2O2-induced oxidative stress and cell apoptosis
      in RPE cells. In addition, pretreatment with SAL significantly increased the
      phosphorylation levels of Akt and GSK-3beta in H2O2-treated ARPE-19 cells. In
      conclusion, the present study demonstrated that SAL protected RPE cells against
      H2O2-induced cell injury through the activation of the Akt/GSK-3beta signaling
      pathway. This suggests that SAL may be a potential therapeutic strategy for the
      treatment of age-related macular degeneration.

PMID- 30210587
TI  - Correlation analysis of intestinal flora with hypertension.
AB  - Relationship between intestinal flora content and hypertension was investigated.
      Ninety-four patients with hypertension who were admitted and treated in No. 215
      Hospital of Shaanxi Nuclear Industry from May 2016 to April 2017 were selected as
      the observation group; and 94 healthy people from the physical examination center
      of No. 215 Hospital of Shaanxi Nuclear Industry in the same time period were
      selected as the control group. The systolic (SBP) and diastolic blood pressure
      (DBP) of all the participants were measured. Reverse transcription-quantitative
      polymerase chain reaction (RT-qPCR) was used to detect the quantities of
      Eubacterium rectale, Bacteroides thetaiotaomicron and Bifidobacterium in the
      intestines, and correlation analyses were performed. The SBP, DBP and content of
      Eubacterium rectale in the observation group were significantly higher than those
      in the control group, while the contents of Bacteroides thetaiotaomicron and
      Bifidobacterium were obviously lower than those in the control group (P<0.05).
      Pearson's correlation analysis showed that Eubacterium rectale was positively
      correlated with SBP and DBP, while Bacteroides thetaiotaomicron and
      Bifidobacterium had a negative correlation with SBP and DBP (P<0.05). The results
      showed that the quantities of Bifidobacterium and Bacteroides thetaiotaomicron
      are decreased while the number of Eubacterium rectale is increased in the
      intestines of patients with hypertension. Moreover, the content of intestinal
      flora has a significant correlation with hypertension.

PMID- 30210589
TI  - Pharmaceutical analysis of different antibiotic regimens in the treatment of
      lower respiratory tract infection.
AB  - The present study aimed to discuss and compare the effects and expenses of
      different antibiotic regimens in the treatment of lower respiratory tract
      infection (LRTI). A retrospective analysis was performed on 200 patients
      diagnosed with LRTI and treated at the Department of Respiratory Medicine of
      Dongying People's Hospital from February 2015 to May 2017. The patients were
      randomly divided into Group A, Group B, Group C and Group D, with 50 cases in
      each group, and were treated with ceftriaxone sodium, ceftizoxime sodium,
      levofloxacin and azithromycin, respectively. Venous blood of patients was
      collected. White blood cells (WBC) of venous blood were detected using a
      hematology analyzer and C-reactive protein (CRP) was tested with latex
      immunoturbidimetry. Moreover, therapeutic effects and drug costs of four
      different antibiotics were compared. No adverse reactions occurred to patients in
      the four groups during the treatment process. The value at each time point after
      treatment was significantly decreased compared with that at the previous time
      point before treatment within the group (P<0.01). The treatment expenses of
      patients in Group A, Group B and Group D were significantly increased compared
      with those in Group C (P<0.01), the treatment expenses of patients in Group B and
      Group D were significantly increased compared with those in Group A (P<0.01) and
      the treatment expenses of patients in Group D were significantly increased
      compared with those in Group B (P<0.01). Ceftriaxone sodium, ceftizoxime sodium,
      levofloxacin and azithromycin all have a good antimicrobial efficacy. The
      treatment condition of LRTI can be dynamically monitored by WBC and CRP which can
      accurately reflect the progression condition of patients' illness and the
      treatment effect. In economic terms, the treatment cost of levofloxacin is the
      lowest; thus, it is worthy of clinical popularization and application.

PMID- 30210590
TI  - Effect of montelukast on the expression of CD4+CD25+ regulatory T cells in
      children with acute bronchial asthma.
AB  - The aim of this study was to investigate the effect of montelukast on the
      expression of CD4+CD25+ regulatory T cells in children with acute bronchial
      asthma. Fifty-six child patients with acute bronchial asthma treated in the
      Department of Pneumology at the Shangluo Central Hospital were selected and
      randomly divided into the control group (n=28) and treatment group (n=28). The
      control group was treated with the conventional therapy of bronchial asthma,
      while the treatment group received montelukast on the basis of the control group
      for 7 days. The clinical symptoms, lung function and proportion of CD4+CD25+
      regulatory T cells in peripheral T lymphocyte subsets in patients in the two
      groups were observed. Moreover, the levels of inflammatory factors and
      immunoglobulin E (IgE) in peripheral blood in both groups were detected. The
      effective treatment rate in the treatment group was significantly higher than
      that in the control group (P<0.05), and the forced expiratory volume in 1
      sec/forced vital capacity (FEV1/FVC), peak expiratory flow (PEF) and 25% peak
      expiratory flow (PEF25) in the treatment group were significantly higher than
      those in the control group (P<0.05). The proportions of CD4+CD25+ regulatory T
      cells in the two groups after drug therapy were significantly increased. The
      proportion and content per unit volume of peripheral CD4+CD25+ regulatory T cells
      in the treatment group were obviously higher than those in the control group
      (P<0.01). After treatment, the levels of interleukin-4 (IL-4), IL-5 and IL-6 in
      peripheral blood in the two groups were significantly decreased. However, the
      levels of transferrin-gamma (TFN-gamma) and IL-10 were significantly increased
      (P<0.01). The IgE level in the treatment group was also significantly higher than
      that in the control group (P<0.01). In conclusion, montelukast can regulate the T
      helper 1 (Th1)/Th2 balance, increase the expression of CD4+CD25+ regulatory T
      cells, and improve the airway inflammation caused by acute bronchial asthma and
      the clinical symptoms and lung function of patients with acute bronchial asthma.

PMID- 30210591
TI  - Hypermethylation of the kappa1 opioid receptor promoter in Chinese heroin and
      methamphetamine addicts.
AB  - Heroin and methamphetamine (METH) addiction continues to be a major social,
      economic and therapeutic problem worldwide. The opioid pathway may mediate the
      effects of addictive drugs. However, the potential correlation between the kappa1
      opioid receptor (OPRK1) and drug addiction has not yet been characterized. The
      aim of the present study was to investigate the potential association between
      methylation of the OPRK1 promoter and substance abuse. Bisulfite pyrosequencing
      technology was used to determine the levels of OPRK1 promoter methylation in 60
      drug abusers (30 heroin and 30 METH addicts) and 52 controls, observed to exhibit
      no significant differences in age or gender. The results indicated that levels of
      OPRK1 promoter methylation were significantly higher in drug addicts when
      compared with controls (P=2.43*10-4). Significant correlations between OPRK1
      promoter methylation and the length and frequency of drug use were also observed
      in male heroin addicts (length: r=0.661, P=0.007; frequency: r=-0.684, P=0.005).
      In addition, a luciferase reporter gene assay indicated that the OPRK1 promoter
      fragment was able to regulate gene expression (fold change between two groups
      >32.12, P<=0.0001). In conclusion, results of the present study indicate that
      methylation of the OPRK1 promoter contributes to the pathophysiology of drug
      addiction.

PMID- 30210592
TI  - In vitro culture and biological properties of broiler adipose-derived stem cells.
AB  - In the past 10 years, adipose-derived stem cells (ADSCs) have been applied due to
      their pluripotency. Experimental tissues have been frequently obtained from
      mammals, including rabbits, mice and humans, but rarely from broilers, Gallus
      gallus domesticus. In the present study, ADSCs were obtained from 20-day-old
      broiler embryos. Primary ADSCs were sub-cultured to passage 37 in vitro. The
      surface markers of ADSCs, namely CD29, CD31, CD44, CD71 and CD73, were detected
      by reverse transcription polymerase chain reaction and immunofluorescence assays.
      The result indicated that CD29, CD44, CD71 and CD73 were expressed on the surface
      of cells at various passages, but not CD31. The growth curve of cells at the
      different passages had a typical sigmoidal shape. Furthermore, ADSCs were
      successfully induced to differentiate into osteoblasts, adipocytes and hepatocyte
      like cells. The results denote that the ADSCs isolated from broilers have similar
      biological properties to those of ADSCs obtained from other animals. The present
      study provided a theoretical and experimental foundation for the use of poultry
      as a source of stem cells, and laid a foundation for adipose tissue engineering
      and strategies in regenerative medicine.

PMID- 30210593
TI  - Vascularization of vessel pedicle in hypospadias and its relationship to near
      period complications.
AB  - The present study evaluated the relationship between the vascularization of
      vessel pedicle and the near-period complication by assessing the surgery effect
      and recognizing the blood supply of the material for urethra reconstruction and
      collected the follow-up of the hypospadias patients after the operation. We
      illuminated the prepuce by a lighting technique using cold light and then
      photographed, and recorded the distribution and the quantity of vessels. Then
      classified, analyzed and summarized the vascularization of vessel pedicle.
      Patients who were repaired by Duckett technique were followed up for 1-5 months
      after the operation. We classified vessel pedicle vascularization in hypospadias
      cases into four patterns based on the predominant blood vessels. The number of
      predominant vessels had no exact relationship to the meatal location. The
      incidence of fistula and stricture had no exact relationship to the number of
      predominant vessels. In conclusion, there is no exact congruent relationship
      between the types of vascularization with the meatal location. Vascularization of
      vessel pedicle had no exact relationship with urethral fistula or stricture.

PMID- 30210594
TI  - Arthroscopic partial capsulotomy for exposure and treatment of hip disease.
AB  - Hip arthroscopy is an effective method for the diagnosis and treatment of hip
      joint pathologies. However, gaining access to the central and peripheral
      compartments is challenging. The present study aimed to assess the advantages of
      using an arthroscopic extra-capsular approach and partial capsulotomy for access
      and subsequent management of hip diseases. Patients subjected to hip arthroscopy
      by partial capsulotomy for exposure and treatment of hip diseases between
      February 2012 and February 2016 were retrospectively analyzed. A total of 32
      patients, including 19 males and 13 females, aged 19-48 years (median age, 36
      years), had undergone the procedure. Firstly, the distal anterior lateral and
      anterolateral arthroscopic approach with blunt dissection was performed.
      Subsequently, a T-shaped partial capsulotomy was established to achieve adequate
      exposure. The shaver, radiofrequency probe and tissue penetrating suture grasper
      were then inserted to perform procedures including debridement of the synovium,
      suturing of the glenoid labrum. During surgery, a probe hook was used to push the
      capsule section limbs or pull the sutures placed on the capsule section limbs to
      improve exposure. For patients with pre-operative anterior instability,
      ligamentous laxity or acetabular dysplasia capsules were sutured to finish
      capsule closure. The pre-operative and post-operative Visual Analogue Scale (VAS)
      score and modified Harris hip score (MHHS) were used to assess the effectiveness
      of the procedure. No obvious post-operative complications were encountered. The
      mean follow-up time was 22.4 months (range, 18-32 months) and 31 patients
      completed the follow-up, while 1 patient was lost to follow-up. Compared with the
      pre-operative score, the MHHS was significantly increased (66.2+/-6.0 vs. 82.6+/
      5.2; P<0.05) and the VAS score was significantly decreased (6.5+/-1.1 vs. 1.2+/
      0.7; P<0.05) at the end of the follow-up. In conclusion, arthroscopic partial
      capsulotomy provides access to the peripheral and central compartments of the hip
      and is a relatively simple technique that is easy to master for surgeons with
      limited experience in hip surgery.

PMID- 30210596
TI  - Quercetin is able to alleviate TGF-beta-induced fibrosis in renal tubular
      epithelial cells by suppressing miR-21.
AB  - Patients with chronic kidney disease (CKD) are characterized by a gradual loss of
      kidney function over time. A number of studies have indicated that tubule
      interstitial fibrosis (TIF) is associated with the occurrence and development of
      CKD. The aim of the present study was to investigate the effect of quercetin
      treatment on the fibrosis of renal tubular epithelial cells and to determine
      whether the anti-fibrotic effects of quercetin are achieved via microRNA (miR)
      21. Human tubular epithelial HK-2 cells were cultured with transforming growth
      factor (TGF)-beta to induce fibrosis and the expression of fibrotic markers
      collagen I, fibronectin, alpha-smooth muscle actin (SMA) and epithelial-cadherin
      were measured using reverse transcription-quantitative polymerase chain reaction
      (RT-qPCR) and western blotting. Cells were treated with 7.5, 15 or 30 mg/ml
      quercetin, following which fibrosis and miR-21 expression were evaluated.
      Quercetin-treated cells were transfected with miR-21 mimics and the expression of
      fibrotic markers was examined using RT-qPCR. Finally, the expression of fibrosis
      associated miR-21 target genes, phosphatase and tensin homolog (PTEN) and TIMP
      Metallopeptidase Inhibitor 3 (TIMP3), was measured in cells treated with
      quercetin with or without miR-21 mimics using RT-qPCR, western blotting and
      immunocytochemistry. The results revealed that TGF-beta treatment induced a
      significant increase in the expression of fibrotic markers in HK-2 cells, while
      quercetin treatment partially inhibited the fibrosis of HK-2 cells. Furthermore,
      quercetin treatment significantly inhibited TGF-beta-induced miR-21 upregulation
      and transfection with miR-21 mimics reversed the anti-fibrotic effects of
      quercetin. Quercetin treatment markedly upregulated PTEN and TIMP3 expression,
      whereas transfection with miR-21 mimics reversed this effect. The results of the
      present study suggest that quercetin is able to alleviate TGF-beta-induced
      fibrosis in HK-2 cells via suppressing the miR-21 and upregulating PTEN and
      TIMP3. Quercetin may have potential as an anti-fibrotic treatment for patients
      with renal fibrosis.

PMID- 30210595
TI  - miRNA-218 regulates the proliferation and apoptosis of cervical cancer cells via
      targeting Gli3.
AB  - Cervical cancer (CC) is one of the most malignant tumors that affect women.
      Recent studies have reported that microRNAs (miRs) serve important roles in CC.
      The aim of the present study was to investigate the role of miR-218 in CC and to
      verify its underlying mechanism. The results of reverse transcription
      quantitative polymerase chain reaction (RT-qPCR) revealed that miR-218 was
      dramatically downregulated in CC tissues and cell lines. Furthermore, the
      expression of Gli3 and Ki67 was measured using RT-qPCR and the results revealed
      that levels of these proteins were negatively correlated with miR-218 in CC
      tissues. The protein expression levels were determined by western blotting. Then
      SiHa cell line was used to investigate the mechanism of CC. Following cell
      transfection, cell apoptosis and cycle analyses were performed using the flow
      cytometry. The results revealed that miR-218 overexpression significantly
      inhibited cell proliferation, apoptosis and cell cycle. Additionally, luciferase
      reporter assay revealed that Gli3 may be a novel and direct target of miR-218 in
      CC. Taken together, the results of the present study suggest that miR-218
      overexpression or Gli3 knockdown may have potential as therapeutic strategies for
      the treatment of CC.

PMID- 30210598
TI  - Values of detection of NF-kappaB activation level combined with IL-6 and TNF
      alpha levels in peripheral neutrophils in the prediction of multiple organ
      dysfunction syndrome in patients with severe multiple trauma.
AB  - The aim of this study was to analyze the dynamic changes and predictive values of
      nuclear factor-kappaB (NF-kappaB) combined with interleukin-6 (IL-6) and tumor
      necrosis factor-alpha (TNF-alpha) in peripheral blood in multiple organ
      dysfunction syndrome (MODS) in patients with severe multiple trauma. Seventy
      patients diagnosed with severe multiple trauma in Emergency Department of Sichuan
      Provincial People's Hospital (Chengdu, China) from April 2014 to April 2016 were
      selected and retrospectively analyzed. The patients enrolled were divided into
      the MODS group (n=25) and the non-MODS group (n=45). The injury severity scores
      (ISSs), acute physiology and chronic health evaluation II (APACHE II) scores, NF
      kappaB, IL-6 and TNF-alpha levels in patients were detected at different time
      points (12, 24 and 48 h after admission), the changes in different indexes and
      the areas under the receiver operating characteristic (ROC) curve (AUC) were
      analyzed. The predictive values of different detection methods in MODS patients
      were discussed and compared. The ISS, APACHE II score, NF-kappaB, IL-6 and TNF
      alpha levels in the MODS group at admission and 24 and 48 h after admission were
      higher than those in the non-MODS group (P<0.05). Those indexes in the deceased
      patients at 12, 24 and 48 h after admission were higher than those in survivors
      (P<0.05). The ISS, APACHE II score, NF-kappaB, IL-6 and TNF-alpha levels were not
      the risk factors of MODS in patients with severe multiple trauma (P>0.05). AUCs
      of ISS >22 points and APACHE II score >14 points in predicting MODS were lower
      than that of combined detection of NF-kappaB >1.20. In conclusion, the combined
      detection of NF-kappaB, IL-6 and TNF-alpha in peripheral blood of patients with
      acute multiple trauma is more helpful to predict the occurrence of MODS, which
      has a certain guiding significance for the prognosis of patients with MODS.

PMID- 30210599
TI  - Mitochondrial damage in hippocampal neurons of rats with epileptic protein
      expression of Fas and caspase-3.
AB  - Epilepsy model in rats was established to observe the behavior and pathological
      changes, and to detect mitochondrial dysfunction, exploring its possible
      molecular mechanisms. The epileptic status of Sprague-Dawley (SD) rats was
      induced by intraperitoneal injection of lithium chloride, and the change of
      behavior was recorded. Electroencephalogram (EEG) was used to measure the
      abnormal discharge of neurons in rats. The brain tissue was fixed with
      polyformaldehyde and the paraffin sections were prepared, and the damage of the
      hippocampal neurons was observed with Nissl staining. Mitochondrial ATP and
      mitochondrial DNA were examined to assess mitochondrial dysfunction. Finally,
      qPCR and western blot analysis were used to detect mRNA and protein expression of
      fatty acid synthetase (Fas), Fas ligand (FasL) and caspase-3 in rat hippocampal
      neurons. The correlation between the mitochondrial dysfunction of rat hippocampal
      neurons and Fas and caspase-3 was analyzed. Compared with the normal group rats,
      the model group showed typical seizures, which were determined by the Racine
      attack score. EEG of the hippocampus of the model group was recorded in cluster
      in model group rats. Nissl staining showed a different degree of damage to the
      hippocampal neurons in the model group compared with normal rats. The
      mitochondrial ATP content and DNA content of rat hippocampal neurons in the model
      group were significantly lower than that of normal rats (P<0.01). The qPCR and
      western blot results showed that the mRNA and protein expression levels of Fas,
      FasL and caspase-3 were significantly increased in the hippocampus of rat model
      group (P<0.01). The expression level of Fas and caspase-3 in hippocampal tissues
      of rats was negatively correlated with mitochondrial DNA content. In conclusion,
      seizures cause damage of neuron mitochondria in rat hippocampus leading to death
      of hippocampal neurons, the mitochondrial damage of hippocampal neurons in
      epileptic rats was closely related to the expression of Fas and caspase-3.

PMID- 30210597
TI  - Screening of genes associated with inflammatory responses in the endolymphatic
      sac reveals underlying mechanisms for autoimmune inner ear diseases.
AB  - The current study analyzed gene expression profiles of the endolymphatic sac (ES)
      in rats and identified expressed genes, present in the human and rat ES, to
      reveal key hubs for inflammatory responses. Microarray data (accession no. E-MEXP
      3022) were obtained from the European Bioinformatics Institute database,
      including three biological replicates of ES plus dura tissues and three
      replicates of pure dura tissues form rats. Differentially expressed genes (DEGs)
      were screened using the Linear Model for Microarray data method and a protein
      protein interaction (PPI) network was constructed using data from the Search Tool
      for the Retrieval of Interacting Genes/Proteins database followed by a module
      analysis via Clustering with Overlapping Neighborhood Expansion. Function
      enrichment analysis was performed using the Database for Annotation,
      Visualization and Integrated Discovery online tool. A total of 612 DEGs were
      identified, including 396 upregulated and 216 downregulated genes. Gene ontology
      term enrichment analysis indicated DEGs were associated with cell adhesion,
      including alpha5-integrin (Itga1) and secreted phosphoprotein 1 (Spp1); T cell co
      stimulation, including C-C chemokine ligand (Ccl)21 and Ccl19; and the toll-like
      receptor signaling pathway, including toll-like receptor (Tlr)2, Tlr7 and Tlr8.
      These conclusions were supported by Kyoto Encyclopedia of Genes and Genomes
      pathway analyses revealing extracellular matrix-receptor interaction, including
      Itga1 and Spp1; leukocyte transendothelial migration, includingclaudin-4 (Cldn4);
      and malaria, including Tlr2. The hub roles of Itga1, Cd24 and Spp1 were revealed
      by calculating three topological properties of the PPI network. Ccl21, Ccl19 and
      Cldn4 were demonstrated to be crucial following significant module analysis
      according to the corresponding threshold, which revealed they were enriched in
      inflammation pathways. Tlr7, Tlr2, granzyme m and Tlr8 were common genes
      associated with inflammatory responses in rat and human ES. In conclusion,
      abnormal expression of the aforementioned inflammation-associated genes may be
      associated with the development of autoimmune inner ear diseases.

PMID- 30210601
TI  - Effect of ranibizumab on levels of IL-6 and VEGF in peripheral blood and aqueous
      humor of glaucoma rat model and association of IL-6 and VEGF with optic nerve
      damage.
AB  - This study aims to investigate the effect of intravitreal injection of
      ranibizumab on glaucoma rat model and its effect on optic nerve injury. A total
      of 125 SD rats were used to establish glaucoma models. Of them, 80 well
      established model were selected, 40 of which received intravitreal injections of
      ranibizumab and were assigned to the observation group. The remaining 40 received
      no drug and were assigned to the control group. After rats were sacrificed at the
      time-points, the retina was harvested. Numbers of retinal ganglion cells (RGCs)
      were counted under a fluorescence microscope. In the meantime, levels of
      interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) in peripheral
      blood and aqueous humor were determined. The levels of IL-6 and VEGF in
      peripheral blood and aqueous humor decreased gradually over the time of treatment
      in the observation group (P<0.05). In the control group the levels of IL-6 in
      peripheral blood and aqueous humor increased gradually over time (P<0.05). At the
      same time-point, the IL-6 level was higher in the control group than that in the
      observation group (P<0.05). The VEGF level in the observation group was lower in
      day 21 than that in day 7 (P<0.05). The VEGF level was higher in the control
      group than that in the observation group (P<0.05). The number of RGCs in the
      observation group increased gradually over the time of treatment, and there were
      significant differences in the number of RGCs between day 7 and 14, as well as
      day 14 and 21 (P<0.05). The number of RGCs in the control group decreased
      gradually over time (P<0.05). The levels of IL-6 and VEGF were all negatively
      correlated with the number of RGCs, and the correlation coefficient r and P-value
      were -0.743 and 0.012, and -0.675 and 0.022, respectively. Ranibizumab attenuated
      optic nerve injury by reducing levels of IL-6 and VEGF in peripheral blood and
      aqueous humor of glaucoma rat model.

PMID- 30210600
TI  - Modified Huangqi Chifeng decoction inhibits excessive autophagy to protect
      against Doxorubicin-induced nephrotic syndrome in rats via the PI3K/mTOR
      signaling pathway.
AB  - The aim of the present study was to investigate whether modified Huangqi Chifeng
      decoction (MHCD) could be an effective treatment against Doxorubicin-induced
      nephrosis in rats and whether it regulates autophagy via the phosphoinositide-3
      kinase/mammalian target of rapamycin (PI3K/mTOR) signaling pathway. A total of 40
      male Sprague-Dawley rats were randomly divided into blank, model, telmisartan and
      MHCD groups. The rat model of nephrosis was induced by intragastric
      administration of Doxorubicin for 8 weeks. Rats were housed in metabolic cages
      and urine was collected once every 2 weeks to measure 24-h protein levels. Blood
      samples were obtained from the abdominal aorta and levels of albumin (ALB), total
      cholesterol (TCH), triacylglyceride (TG) and serum creatinine (Scr) were
      assessed. Renal pathological changes were examined using hematoxylin-eosin,
      Masson's trichome and periodic acid-Schiff staining. Podocytes and autophagosomes
      were observed using an electron microscope. The expression and distribution of
      microtubule-associated proteins 1A/1B light chain 3B (LC3), LC3-I, LC3-II, beclin
      1, PI3K and mTOR were determined using immunohistochemistry and western blotting.
      At weeks 6 and 8, 24-h proteinuria significantly decreased in the MHCD group
      compared with the model group (P<0.05). Compared with the model group, the MHCD
      group exhibited significantly reduced levels of TG, TCH and Scr, as well as
      significantly increased ALB levels (P<0.05). MHCD was demonstrated to prevent
      glomerular and podocyte injury. The number of autophagosomes was significantly
      decreased and the expression of beclin-1, LC3, LC3-I and LC3-II was inhibited
      following MHCD treatment compared with the model group (P<0.05). MHCD treatment
      significantly increased the expression of PI3K and mTOR in Doxorubicin nephrotic
      rats compared with the model group (P<0.05). In conclusion, MHCD was demonstrated
      to ameliorate proteinuria and protect against glomerular and podocyte injury by
      inhibiting excessive autophagy via the PI3K/mTOR signaling pathway.

PMID- 30210602
TI  - Automated nasopharyngeal carcinoma segmentation in magnetic resonance images by
      combination of convolutional neural networks and graph cut.
AB  - Accurate and reliable segmentation of nasopharyngeal carcinoma (NPC) in medical
      images is an import task for clinical applications, including radiotherapy.
      However, NPC features large variations in lesion size and shape, as well as
      inhomogeneous intensities within the tumor and similar intensity to that of
      nearby tissues, making its segmentation a challenging task. The present study
      proposes a novel automated NPC segmentation method in magnetic resonance (MR)
      images by combining a deep convolutional neural network (CNN) model and a 3
      dimensional (3D) graph cut-based method in a two-stage manner. First, a multi
      view deep CNN-based segmentation method is performed. A voxel-wise initial
      segmentation is generated by integrating the inferential classification
      information of three trained single-view CNNs. Instead of directly using the CNN
      classification results to achieve a final segmentation, the proposed method uses
      a 3D graph cut-based method to refine the initial segmentation. Specifically, the
      probability response map obtained using the multi-view CNN method is utilized to
      calculate the region cost, which represents the likelihood of a voxel being
      assigned to the tumor or non-tumor. Structure information in 3D from the original
      MR images is used to calculate the boundary cost, which measures the difference
      between the two voxels in the 3D neighborhood. The proposed method was evaluated
      on T1-weighted images from 30 NPC patients using the leave-one-out method. The
      experimental results demonstrated that the proposed method is effective and
      accurate for NPC segmentation.

PMID- 30210603
TI  - Effects of SB202190 on expression levels of IL-6 and NF-kappaB in flap ischemia
      reperfusion injury.
AB  - The aim of the current study was to investigate the effect of SB202190, a
      specific inhibitor of p38 MAPK signaling pathway, on the expression levels of IL
      6 and NF-kappaB in flap ischemia-reperfusion injury. Healthy Sprague-Dawley rats
      were randomly divided into four groups of 12 each. For the ischemia-reperfusion
      group, the flap was constructed and then sutured after 8 h of ischemia. For the
      saline group, rats were intraperitoneally infused with saline at regular
      intervals after flap ischemia-reperfusion. For the inhibitor group, rats were
      intraperitoneally infused with SB202190 at regular intervals after flap ischemia
      reperfusion. For the control group, the flap was constructed and then sutured
      immediately. The flap survival rate of each group was measured after 7 days. The
      concentration of IL-6 in serum was measured by ELISA kit. The mRNA and protein
      expression levels of IL-6 and NF-kappaB in the flap were measured using RT-PCR
      and western blot analysis, respectively. In the ischemia-reperfusion group and
      the saline group, the flap survival rates were much lower than that in the
      control group (P<0.05). By contrast, the mRNA and protein expression levels of IL
      6 and NF-kappaB in the flap and the concentration of IL-6 in serum were much
      higher (P<0.05). In the inhibitor group, the flap survival rate was significantly
      higher than those in the ischemia-reperfusion and saline groups (P<0.05). By
      contrast, the concentration of IL-6 in serum and the mRNA and protein expression
      levels of NF-kappaB and IL-6 in the flap were significantly decreased (P<0.05).
      The results show that, SB202190 played a role in the protection of the flap by
      reducing the inflammatory response in flap ischemia-reperfusion injury.

PMID- 30210604
TI  - Meta-analysis of the benefit of sitagliptin treatment in patients with type 2
      diabetes complicated with incipient nephropathy.
AB  - The purpose of this meta-analysis was to evaluate the evidence of the clinical
      efficacy and safety of sitagliptin in diabetic patients with incipient
      nephropathy. PubMed, Ovid, Cochrane library, Chinese National Knowledge
      Infrastructure, and Wanfang databases were searched in September 2017 to identify
      randomized controlled trials (RCTs) of sitagliptin in diabetic patients with
      incipient nephropathy. Study selection, data extraction and study quality
      assessment were performed independently by two investigators, while disagreements
      were resolved by a third reviewer. The treatment effect was estimated by
      calculating the mean difference (MD) or standard mean difference (SMD).
      Heterogeneity was assessed with the chi2 and I2 tests. Additionally, risk of bias
      graphs and summaries were used to assess the quality of the included trials.
      Thirteen RCTs were included in this review; their results suggested that
      sitagliptin has obvious advantages in lowering the 24-hour urinary albumin
      excretion [MD, -25.71; 95% confidence interval (CI), -30.75 to -20.66;
      P<0.00001], serum cystatin C (MD, -0.59; 95% CI, -0.64 to -0.54; P<0.00001),
      inflammation (MD, -0.81; 95% CI, -1.20 to -0.42; P<0.0001), and total cholesterol
      (MD, -0.13; 95% CI, -0.22 to -0.03; P=0.009). However, sitagliptin did not appear
      to influence serum creatinine, fasting blood glucose, postprandial blood glucose,
      glycosylated hemoglobin A1c, or triglyceride levels, although these results may
      have been influenced by biases in the included trials. The most common adverse
      effects of sitagliptin were gastrointestinal tract reaction and hypoglycemia,
      although these symptoms resolved quickly. Sitagliptin appears to be effective in
      reducing proteinuria, ameliorating renal function, and producing an anti
      inflammatory effect in patients with early-stage diabetic nephropathy. The
      present analysis provides important guidance for the clinical application of
      sitagliptin.

PMID- 30210605
TI  - Effects of hepatic blood inflow on liver ultrastructure and regeneration after
      extensive liver resection in rats with cirrhosis.
AB  - The aim of the present study was to investigate the effects of hepatic blood
      inflow on liver function, liver ultrastructure and the regeneration of future
      liver remnant (FLR) following major hepatectomy in rats with liver cirrhosis. A
      rat model of cirrhosis was established through intraperitoneal injection of
      carbon tetrachloride for 8 consecutive weeks. Extensive liver resection and
      different blood inflow models by portal vein (PV) and/or hepatic artery (HA)
      stenosis were conducted on the cirrhosis rats. Animal models were constructed as
      follows: Control (group A), low-flow PV + high-flow HA (group B), low-flow PV +
      low-flow HA (group C), high-flow PV + high-flow HA (group D) and high-flow PV +
      low-flow HA (group E). Hepatic blood inflow was detected by laser speckle
      contrast analysis, liver function and pathological changes were analyzed, Masson
      staining was used to identify the fibrosis of the liver and Periodic acid-Schiff
      staining was used to identify glycogen synthesis and hepatocyte function. The
      liver cell ultrastructure was evaluated by transmission electron microscopy, and
      the expression of Ki-67 in hepatocytes and the weight of the FLR were recorded to
      determine the regeneration of the FLR. Five days after major hepatectomy and
      liver blood inflow modulation, pathological examination of the livers from groups
      B and C revealed less congestion and less extensive hepatocellular injury. The
      serum alanine aminotransferase level of group B at 1, 3 and 5 days after
      hepatectomy and blood inflow modulation was 460.9+/-31.7, 331.0+/-22.0 and
      285.6+/-15.8 U/l, respectively (control group: 676.9+/-41.7, 574.9+/-28.0 and
      436.1+/-32.7 U/l, respectively; P<0.05); the total bilirubin of group B at 1, 3
      and 5 days was 20.4+/-1.5, 16.1+/-1.0 and 13.5+/-0.6 umol/l, respectively
      (control group: 30.3+/-1.4, 26.5+/-0.8 and 22.1+/-1.2 umol/l, respectively;
      P<0.05). The size of the endoplasmic reticulum in the low-flow PV groups
      increased significantly and the mitochondrial swelling was alleviated. The
      positive rate of Ki-67 in the hepatocytes of groups B, C and D was 23.9+/-3.6,
      15.7+/-2.3 and 12.9+/-2.4%, respectively (control group: 10.1+/-2.1%, P<0.05),
      and the positive rate of Ki-67 in group E was 6.1+/-1.4% (compared with that of
      the control group, P<0.05). The remnant liver weight of group B was 15.4+/-1.0 g
      (compared with that of the control group, P<0.05). Therefore, decreased portal
      blood flow combined with increased hepatic arterial blood flow alleviated the
      congestion in the liver following major hepatectomy in cirrhotic rats, improved
      the pathological status and liver function, increased the expression of Ki-67 and
      promoted liver regeneration.

PMID- 30210606
TI  - Analyzing the disease module associated with osteosarcoma via a network- and
      pathway-based approach.
AB  - Osteosarcoma is the most common type of primary malignant bone tumor observed in
      children and adolescents. The aim of the present study was to identify an
      osteosarcoma-related gene module (OSM) by looking for a dense module following
      the integration of signals from genome-wide association studies (GWAS) into the
      human protein-protein interaction (PPI) network. A dataset of somatic mutations
      in osteosarcoma was obtained from the dbGaP database and their testing P-values
      were incorporated into the PPI network from a recent study using the dmGWAS
      bioconductor package. An OSM containing 201 genes (OS genes) and 268
      interactions, which were closely associated with immune response, intracellular
      signal transduction and cell activity was identified. Topological analysis of the
      OSM identified 11 genes, including APP, APPBP2, ATXN1, HSP90B1, IKZF1, KRTAP10-1,
      PAK1, PDPK1, SMAD4, SUZ12 and TP53 as potential diagnostic biomarkers for
      osteosarcoma. The overall survival analysis of osteosarcoma for those 11 genes
      based on a dataset from the Cancer Genome Atlas, identified APP, HSP90B1, SUZ12
      and IKZF1 as osteosarcoma survival-related genes. The results of the present
      study should be helpful in understanding the diagnosis and treatment of
      osteosarcoma and its underlying mechanisms. In addition, the methodology used in
      the present study may be suitable for the analysis of other types of disease.

PMID- 30210607
TI  - Magnetic wires: A novel design for neuroendovascular coil retrieval.
AB  - The present study aimed to evaluate the operation, application and safety of a
      novel prototype device designed for the retrieval of a migrated coils, an
      intraprocedural complication of endovascular aneurysm treatment, compared with
      the widely used Solitaire AB stent retriever. The prototype retrieval device,
      referred to as magnetic wires, consisted of two microwires that were joined by a
      small magnetic ring near to the tips. To retrieve a coil, the wires are advanced
      through the dislodged coil one at a time and then capture the target coil in a
      chopstick-like manner, as their tips are attracted to the magnet. In vitro tests
      were performed five times for each retrieval device using a pulsing flow
      circulator to compare retrieval effectiveness. In vivo efficacy testing was
      performed in 5 male piglets. The left and right carotid arteries were used to
      assess the magnetic wires and the Solitaire retriever, respectively. While the
      two devices successfully retrieved coils in vitro at a rate of 100%, the magnetic
      wires did so in a shorter time. In vivo, the magnetic wires successfully captured
      the migrated coils in 3/5 cases (60%), whereas the Solitaire AB stent retriever
      was successful 4/5 cases (80%). Endothelial injury was observed following
      magnetic wires retrieval in 1/5 cases (20%) and following use of the Solitaire AB
      stent retriever in 3/5 cases (60%). These results demonstrate the feasibility and
      safety of this novel prototype coil retrieval device, which with further
      development has the potential to be an optimal device for the retrieval of
      dislodged coils.

PMID- 30210609
TI  - Recurrent cerebellar infarction associated with hereditary heterozygous protein C
      deficiency in a 35-year-old woman: A case report and genetic study on the
      pedigree.
AB  - Deficiency of protein C may cause deep venous thrombosis and pulmonary embolism,
      leading to ischemic stroke. The present study reports on a case of a young adult
      with recurrent cerebellar infarction due to hereditary heterozygous protein C
      deficiency and performs a literature review. A 35-year-old Asian woman was
      admitted t o the Department of Neurology of The First Affiliated Hospital of
      Guangxi Medical University (Nanning, China) due to right limb paralysis and
      vomiting. The diagnosis of stroke was confirmed by computed tomography and
      magnetic resonance imaging, which indicated acute cerebral infarction of the
      right cerebellar hemisphere and cerebellar vermis, as well as a previous cerebral
      infarction on the left cerebellar hemisphere. This patient had taken aspirin
      orally for 4 years following surgical therapy for small intestine thrombosis and
      was regularly taking hydroxychloroquine sulfate to treat systemic lupus
      erythematosus. The protein C (PROC) levels were 57.6%, while protein S and
      antithrombin levels were normal. Gene sequencing analysis of the patient and the
      patient's pedigree revealed a heterozygous mutation, c.565C>T, on the PROC gene
      in the patient and the patient's father. In conclusion, the clinical
      manifestations of hereditary PROC deficiency may vary between individuals. The
      heterozygous mutation locus c.565C>T on the PROC gene is associated with
      thrombophilia. Awareness of the association between natural anticoagulants and
      thrombophilia may promote the prevention and therapy of stroke.

PMID- 30210608
TI  - Neuroprotective effect of recombinant adeno-associated virus human thioredoxin
      PR39 on acute cerebral infarction in rats.
AB  - The recombinant adeno-associated virus human thioredoxin-PR39 (rAAV/hTRX-PR39)
      has been demonstrated to have a protective effect on hypoxic cells. The present
      study aimed to explore the potential effect of rAAV/hTRX-PR39 on acute cerebral
      infarction in rats. Middle cerebral artery occlusion (MCAO) model rats were
      produced and divided into three groups: Normal saline group, empty virus group
      (rAAV, without hTRX-PR39 cDNA) and rAAV/hTRX-PR39 group. Hematoxylin and eosin
      staining and electron microscopy observation were used to assess the
      morphological changes of ischemic brain tissue during different periods.
      Immunohistochemistry was employed to detect the expression of CD34 to reflect
      angiogenesis of ischemic brain tissue. Rats treated with rAAV/hTRX-PR39 showed an
      alleviated degree of ischemic brain edema relative to that in control groups,
      suggesting PR39 can ameliorate brain damage after cerebral ischemia. In the
      rAAV/hTRX-PR39 group, CD34-positive cells were significantly increased in
      ischemic brain tissues compared to control groups. Furthermore, CD34-positive
      cells were primarily observed around the perivascular in ischemic brain,
      indicating the angiogenesis role of PR39 in ischemic brain. The present findings
      suggest that PR39 could effectively ameliorate ischemic brain damage and promote
      angiogenesis, which may contribute to the treatment of acute cerebral infarction.

PMID- 30210610
TI  - Acetylpuerarin inhibits oxygen-glucose deprivation-induced neuroinflammation of
      rat primary astrocytes via the suppression of HIF-1 signaling.
AB  - In the central nervous system (CNS), ischemic injury induced by inflammation
      associated with astrocytes serves an important role in physiological and
      pathological processes. Neuroinflammation leads to the release of pro
      inflammatory cytokines, including tumor necrosis factor-alpha and interleukin
      1beta. The aim of the present study was to investigate whether acetylpuerarin
      attenuates oxygen-glucose deprivation (OGD)-induced astrocyte inflammation and
      secretion of pro-inflammatory cytokines via inhibiting hypoxia-inducible factor-1
      (HIF-1) activation and suppressing downstream primary astrocyte signaling in
      rats. The results demonstrated that acetylpuerarin attenuates astrocyte viability
      and induces morphological changes following OGD stress. Furthermore,
      acetylpuerarin suppresses the stimulation of HIF-1alpha and nuclear factor (NF)
      kappaB signaling pathways, while attenuating the expression and secretion of pro
      inflammatory cytokines via HIF-1 suppression in OGD-induced astrocytes. These
      findings indicate that acetylpuerarin may attenuate OGD-induced astrocyte damage
      and inflammation in rat primary astrocytes via suppressing HIF-1 activation and
      NF-kappaB signaling. These results suggest that acetylpuerarin regulates
      inflammation associated with astrocytes and may represent a novel therapeutic
      agent for the treatment of neuroinflammation in the CNS.

PMID- 30210611
TI  - Overexpression of microRNA-936 suppresses non-small cell lung cancer cell
      proliferation and invasion via targeting E2F2.
AB  - MicroRNA (miR)-936 has been reported to inhibit the cell cycle and glioma cell
      proliferation. However, the roles of miR-936 in other human tumors remain largely
      unknown. In the present study, it was indicated that miR-936 was significantly
      downregulated in non-small cell lung cancer (NSCLC) tissues compared with
      adjacent normal tissues by reverse transcription-quantitative polymerase chain
      reaction (RT-qPCR). Results also indicated that miR-936 was downregulated in
      NSCLC cell lines compared with 16HBE cells. Furthermore, it was demonstrated that
      overexpression of miR-936 significantly inhibited the proliferation, cell cycle
      progression and invasion of NSCLC cells. Notably, E2F2 was identified as a target
      gene of miR-936 in NSCLC cells. The results indicated that E2F2 was upregulated
      in NSCLC tissues and cell lines, and its expression was negatively correlated
      with that of miR-936 in NSCLC tissues. Overexpression of miR-936 significantly
      reduced the protein expression levels of E2F2 in NSCLC cells. Furthermore,
      restoration of E2F2 rescued the proliferation and invasion of NSCLC cells
      transfected with miR-936 mimics. To the best of our knowledge, the present
      findings demonstrated for the first time that miR-936 suppressed NSCLC
      progression by directly targeting E2F2.

PMID- 30210612
TI  - Overexpression of CD64 on CD14++CD16- and CD14++CD16+ monocytes of rheumatoid
      arthritis patients correlates with disease activity.
AB  - It is well-known that monocytes are a heterogeneous cell population and different
      monocyte subsets play important roles in rheumatoid arthritis (RA). Cluster of
      differentiation (CD)64 is one of Fc receptor, which initiates immunological and
      inflammatory reactions. However, the roles in RA remain to be elucidated. In the
      present study, the expression of CD64, CD40, CD163, CD206, HLA-DR, CD80 and CD86
      on monocytes and the expression of CD64 on monocyte subsets were determined by
      flow cytometry. The expression of CD64 on monocyte subsets in patients with RA
      was further analyzed for their correlation with markers of autoimmune response,
      inflammation, disease activity of RA and serum cytokines. Compared to the health
      volunteers, the expression of CD64 on monocytes and each monocyte subset were
      significantly elevated in RA patients. The expression of CD64 on CD14++CD16- and
      CD14++CD16+ monocytes were positively correlated with erythrocyte sedimentation
      rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), anti-citrullinated
      protein antibodies (ACPA) and disease activity score 28 (DAS28). Furthermore, the
      expression of CD64 on CD14++CD16+ monocytes was found to be associated with the
      serum level of IL-6. In conclusions, these data demonstrated the expression of
      CD64 on CD14++CD16- and CD14++CD16+ monocytes are elevated and associated with
      the disease activity in RA.

PMID- 30210613
TI  - Adiponectin is valuable in the diagnosis of acute heart failure with renal
      insufficiency.
AB  - Acute heart failure (AHF) is a major public health issue due to its high
      incidence and poor prognosis; thus, efficient and timely diagnosis is critical
      for improving the prognosis and lowering the mortality rate. Amino-terminal pro
      brain natriuretic peptide (NT-proBNP) is widely used in the diagnosis of AHF;
      however, its efficacy is controversial in diagnosing AHF with renal
      insufficiency. There were numerous studies reporting the association of
      adiponectin (ADPN) and heart diseases. Therefore, the present study aimed to
      investigate whether ADPN is helpful in identifying AHF with renal insufficiency.
      A total of 407 participants (218 AHF patients and 189 controls) were enrolled
      into the current study. The plasma levels of ADPN and NT-proBNP were measured
      using a sandwich enzyme-linked immunosorbent assay and an
      electrochemiluminescence immunoassay, respectively. In addition, these levels
      were compared among the various New York Health Association classes, as well as
      the ischemic and non-ischemic AHF cases. The correlation between the two
      biomarkers and the renal function was analyzed by Spearman's correlation, while
      the diagnostic efficiency of ADPN and NT-proBNP was evaluated in AHF patients
      with and without renal insufficiency. The results revealed that NT-proBNP
      exhibited a higher diagnostic efficiency as compared with ADPN in patients
      without renal insufficiency [area under the receiver operating characteristic
      curve (AUC), 0.905 vs. 0.775]. By contrast, the ADPN presented a better
      diagnostic value in comparison with NT-proBNP in AHF with renal insufficiency
      (AUC, 0.872 vs. 0.828). Therefore, a combination of these two biomarkers may
      provide an excellent efficacy in the diagnosis of AHF with renal insufficiency
      (AUC, 0.904; sensitivity, 71.2%; specificity, 98.3%). In conclusion, ADPN is a
      valuable biomarker for diagnosing AHF, particularly in patients with impaired
      renal function.

PMID- 30210614
TI  - Phosphatidylinositol 3-kinase-mediated HO-1/CO represses Fis1 levels and
      alleviates lipopolysaccharide-induced oxidative injury in alveolar macrophages.
AB  - Sepsis-related acute respiratory distress syndrome is characterized by marked
      oxidative stress and mitochondrial dysfunction lacking of specific therapy. Heme
      oxygenase (HO)-1 followed by endogenous carbon monoxide (CO) exerted a
      cytoprotective effect against multi-organ damage during sepsis. Additionally, the
      phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway, which serves
      as an upstream regulator of HO-1, was associated with inflammation and oxidative
      stress. Therefore, the purpose of the present study was to investigate whether
      the PI3K/Akt pathway was involved in the effects of HO-1/CO on the expression of
      mitochondrial fission 1 protein (Fis1). In the present study, CO releasing
      molecule-2 (CORM2), as the exogenous source of CO, plus LY294002, as a specific
      PI3K inhibitor, were pre-incubated in lipopolysaccharide (LPS)-simulated rat
      NR8383 alveolar macrophages. The results demonstrated that CORM2 improved cell
      viability, inhibited tumor necrosis factor-alpha levels, malondialdehyde
      contents, while elevating interleukin-10 levels and superoxide dismutase
      activities. In addition, pretreatment with CORM2 suppressed the fragmentation of
      mitochondria, upregulated the expressions of phosphorylated-Akt and HO-1 but
      downregulated the levels of Fis1 mRNA and protein in LPS-exposed cells. However,
      pretreatment with LY294002 significantly inhibited the phosphorylation of Akt,
      decreased HO-1 levels, aggravated mitochondrial fragmentation, increased Fis1
      mRNA and protein levels, and reversed the above protective effects of CORM2.
      Collectively, the results of the present study indicated that the PI3K/Akt
      pathway mediated the cytoprotective effects of HO-1/CO on the transcription and
      translational levels of Fis1, and alleviated LPS-induced oxidative injury in
      alveolar macrophages.

PMID- 30210616
TI  - Verteporfin enhances the sensitivity of LOVO/TAX cells to taxol via YAP
      inhibition.
AB  - Studies have reported that taxol (TAX) is an effective drug for the treatment of
      colorectal cancer; however, its application inevitably results in drug
      resistance. Overexpression of Yes-associated protein (YAP) is considered one of
      the factors that cause TAX resistance, which may be inhibited by verteporfin (VP)
      treatment. The present study aimed to confirm the role of YAP in TAX resistance
      and to investigate whether the drug sensitivity of the TAX-resistant LOVO/TAX
      cell line to TAX is affected by VP treatment. The role of YAP in TAX resistance
      was first determined through vector-mediated overexpression and inhibition of YAP
      in cells. Reverse-transcription quantitative polymerase chain reaction and
      western blot analysis were performed for detection of associated mRNA and
      protein, respectively. An MTT assay was used to detect the drug sensitivity of
      cells to TAX. The results suggested that compared with that in the native LOVO
      cell line, YAP expression was significantly increased in LOVO/TAX cells. YAP gene
      silencing markedly enhanced the drug sensitivity of LOVO/TAX cells to TAX and, on
      the contrary, the drug sensitivity notably declined when YAP was overexpressed in
      LOVO cells. The results indicated that YAP gene expression and TAX resistance
      were correlated. VP treatment suppressed YAP expression and increased the drug
      sensitivity of LOVO/TAX cells to TAX in a dose-dependent manner. In addition,
      compared with VP alone, VP and TAX combination therapy had a greater inhibitory
      effect on YAP expression. VP treatment enhanced the drug sensitivity of LOVO/TAX
      cells to TAX through inhibiting YAP expression.

PMID- 30210615
TI  - Efficacy and tolerability of interferon-free regimen for patients with genotype-1
      HCV infection.
AB  - Depression is a major reason for interferon (IFN) therapy cessation. IFN-free
      direct-acting antiviral (DAA) therapy for depression is not well-documented.
      Thus, four different IFN-free regimens were assessed in genotype-1 hepatitis C
      virus (HCV) patients with depression. Overall, 287 HCV genotype-1 patients who
      received combination therapies with IFN-free DAAs of daclatasvir/asunaprevir
      (DCV/ASV) (n=84), sofosbuvir/ledipasvir (SOF/LDV) (n=95),
      ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) (n=74), and elbasvir/grazoprevir
      (EBR/GZR) (n=34) were included. Treatment-induced depression as a complication of
      HCV therapy in IFN-free DAA regimens was assessed. The severity of depression was
      evaluated using the Beck Depression Inventory-II (BDI-II) questionnaire. It was
      demonstrated that all four DAA regimens achieved similar high efficacy in
      Japanese patients with HCV genotype-1 infection. Moreover, in seven patients with
      depression who received the 24-week DCV/ASV treatment regimen, the BDI-II scores
      significantly increased at week 4 as compared with pretreatment values;
      furthermore, they decreased below baseline at week 12 despite the rapid decline
      of serum HCV levels after the initiation of DCV/ASV therapy. The BDI-II scores
      gradually decreased during therapy in the remaining 77 DCV/ASV-treated patients
      without depression. The BDI-II scores showed a significant decrease from baseline
      to the end of treatment with 12-week regimens, including SOF/LDV and EBR/GZR. The
      12-week DAA regimen of SOF/LDV and EBR/GZR can be safely used with high efficacy
      in patients with genotype-1 HCV infection, including those with depression.

PMID- 30210618
TI  - Tuberculous meningitis diagnosis and treatment in adults: A series of 189
      suspected cases.
AB  - The present study aimed to summarize the clinical features, alterations in
      cerebrospinal fluid (CSF), imaging characteristics, diagnostic methods, treatment
      regimens and outcomes of adult Chinese patients with tuberculous meningitis
      (TBM). Clinical data of 189 cases with 4 cases confirmed with definite TBM, 65
      cases of probable (diagnostic score, >=12 with imaging or >=10 without imaging)
      and 120 cases of possible (diagnostic score, 6-11 with imaging or 6-9 without
      imaging) TBM admitted to Xiangya Hospital of Central South University between
      January 2009 and January 2015 were investigated retrospectively. Data on the
      clinical, laboratory and demographic characteristics of patients, as well as the
      results of radiological investigations and the clinical outcome, were collected
      for all patients. A total of 89.9% patients illustrated symptoms of acute or sub
      acute TBM. The most frequent symptoms and signs were fever (78.3%), headache
      (89.2%), decreased level of consciousness (48.1%), meningeal irritation (73%),
      impairment of cranial nerve function and increased intracranial pressure (60%).
      The CSF protein concentration was significantly elevated and CSF glucose was
      greatly decreased in these cases. Imaging data were available for 144 cases, with
      66 cases presenting abnormal chest X-ray or computed tomography findings, and 127
      cases presenting abnormal brain magnetic resonance imaging findings among the 144
      patients examined. All patients received anti-tuberculosis (TB) therapy, while 7
      patients underwent neurosurgical drainage due to hydrocephalus and 3 patients
      succumbed to the disease. Among the survivors, 87% presented significant
      improvement. In conclusion, the diagnosis of TBM should combine clinical
      manifestations, CSF examination and the effect of anti-TB therapy. Differential
      diagnosis and trial anti-TB therapy may be of help for diagnosis. Positive CSF
      smear, CSF culture and biopsy of the brain, or biopsy of meninges are golden
      standards for the diagnosis of TBM. Early diagnosis and treatment are very
      important for improving the outcome.

PMID- 30210617
TI  - Icariin prevents cytokine-induced beta-cell death by inhibiting NF-kappaB
      signaling.
AB  - The loss of insulin secretion in type I diabetes mellitus (T1DM) is caused by
      autoimmune-mediated destruction of insulin-producing pancreatic beta-cells.
      Inflammatory cytokines and immune cell infiltration activate oxidative and
      endoplasmic reticulum (ER) stress, resulting in reduced beta-cell viability. The
      current pharmacological agents used to control blood glucose have a limited
      effective duration and are accompanied by strong side effects. Blocking the
      inflammatory and immune responses that cause the beta-cell damage has been
      investigated as a novel therapeutic approach to control T1DM. Icariin is a
      flavonoid component of Chinese medicinal herbs that has anti-inflammatory effects
      in vitro and in vivo. The results of the present study revealed that icariin
      abrogates the pro-apoptotic effect of inflammatory cytokines and significantly
      suppresses the activation of nuclear factor (NF)-kappaB in rat pancreatic beta
      cell lines. The present study may provide a basis for the potential use of
      icariin as a therapeutic agent for T1DM.

PMID- 30210619
TI  - Paediatric virology as a candidate of paediatric subspecialisation: An interview
      with Assistant Professor of Molecular Microbiology-Virology Angeliki Melidou.
AB  - According to Professor Angeliki Melidou, Assistant Professor of Molecular
      Microbiology-Virology at the School of Medicine of the Aristotle University of
      Thessaloniki in Greece, recent advances in modern virology have important
      implications in the successful clinical management of neonatal and paediatric
      viral infections. On the other hand, preventive measures for infectious diseases
      and their complications, including vaccinations, proper regular examinations and
      early diagnosis, are equally crucial. Molecular genetics reveals a new era both
      in the detection of viral infections and in following up the infection and
      treatment, as well as identifying genetic predisposition that would affect
      disease course and outcome. Professor Melidou supports that paediatric virology
      as a candidate of paediatric subspecialisation would definitely play an important
      role in preparing specialised medical scientists. These scientists would be
      properly educated for the management of emerging and re-emerging viral
      infections, treatment options and schemes according to children's special needs,
      available prevention strategies and diagnostic capacities. In the context of the
      '4th Workshop on Paediatric Virology', Professor Melidou's lecture will focus on
      the epidemiology of influenza virus types and subtypes in childhood.

PMID- 30210620
TI  - Impact of menopausal status and HER-2/neu protein on efficacy of EGFR-TKI in EGFR
      mutant patients with non-small cell lung cancer.
AB  - Clinical studies have confirmed epidermal growth factor receptor (EGFR)-tyrosine
      kinase inhibitors (TKIs) used in lung cancer patients with EGFR mutations can
      obtain a better result, but still part of the patients with poor efficacy. EGFR
      mutation is highly related to female, nonsmoking and adenocarcinoma. Thus, we
      hypothesize that estrogen and circulating HER-2/neu protein might influence the
      efficacy of EGFR-TKIs in EGFR mutant patients with non-small cell lung cancer.
      HER-2/neu expression level of 357 eligible patients in its peripheral serum was
      determined using ELISA. The median progression-free survival (PFS) in five groups
      (premenopausal group, perimenopause group, peri to postmenopausal group,
      postmenopausal group and control group) was statistically difference (P = 0.025).
      Premenopausal group could predict the efficacy of EGFR-TKI (HR = 2.45, 95% CI =
      1.42-4.23, P = 0.001). No statistical significance was found in median overall
      survival (OS) among five groups. Optimal diagnostic cut off value of HER-2/neu
      was set at 47.5 ng/ml, with P = 0.0607. As the cutoff value to 47.5 ng/ml
      division, concentrations and menopausal status was of no significant difference
      (P = 0.874). PFS of the group below 47.5 ng/ml was significantly longer than that
      of the group over 47.5 ng/ml (P = 0.000). HER-2/neu concentration was positively
      correlated with optimal efficacy (P = 0.042). HER-2/neu concentration over than
      47.5 ng/ml was a risk factor of EGFR-TKI prognosis. Premenopausal status is an
      independent predictor of EGFR-TKI curative effect and circulating HER-2/neu
      protein is an independent prognostic factor in patients with advanced NSCLC.

PMID- 30210621
TI  - Loss of UHRF2 Is Associated With Non-small Cell Lung Carcinoma Progression.
AB  - Recent evidence indicated ubiquitin like with PHD and ring finger domains 2
      (UHRF2) was involved in various human diseases, especially in cancer, however,
      its roles in cancer are still in dispute. Here, we found UHRF2 expression was
      decreased in lung cancer tissues compared with adjacent normal tissues by
      referring to the Oncomine Database, which was further identified by
      immunoblotting and quantitative real-time polymerase chain reaction assays.
      Secondly, we found knockdown of UHRF2 in A549 and 95-D cell lines enhanced the
      capability of proliferation, invasion and migration, while forced UHRF2
      expression inhibited NSCLC cells proliferation,invasion and migration.
      Mechanistically, dot-blot and western blot assays indicated that the level of
      UHRF2 was positively correlated with 5-hmC level by affecting ten-eleven
      translocation 2 (TET2) expression. Clinically, UHRF2 downregulation is
      significantly correlated with a malignant phenotype, including larger tumor size
      and poor differentiation. Moreover, UHRF2 downregulated correlates with shorter
      overall survival(OS). Conclusion: Our findings indicate that UHRF2 is a tumor
      suppressor in NSCLC by influence TET2 expression and serve as a potential
      therapeutic target in NSCLC.

PMID- 30210622
TI  - Identification of microRNA-124 in regulation of Hepatocellular carcinoma through
      BIRC3 and the NF-kappaB pathway.
AB  - MicroRNAs (miRNAs) being proved to be involved in the carcinogenesis of numerous
      tumors. MicroRNA-124 (miR-124), identified as a tumor suppressor, has been
      demonstrated to exert pivotal roles in multiple processes of tumorigenesis. The
      present study demonstrated that miR-124 was low-expressed in human hepatocellular
      carcinoma (HCC) tissues and cell lines. In addition, overexpression of miR-124
      through infected with miR-124 lentivirus inhibited the proliferation and
      migration of HCC in vitro and tumorigenesis in vivo, whereas inhibition of miR
      124 expression can reverse the process. Moreover, Baculoviral IAP Repeat
      Containing 3 (BIRC3) was identified as a target gene of miR-124. The BIRC3 mRNA
      expression was increased in HCC tissues and negatively correlated with miR-124
      expression. Knockdown of BIRC3 recovered the miR-124-induced inhibiting effect on
      HCC progression. Furthermore, we found that up-regulation of miR-124
      significantly inhibited p-P65, p-IkappaBalpha and c-Myc proteins expression.
      However, the effect of miR-124 up-regulation on HCC development was partly
      reversed by BIRC3 restoration. In conclusion, our data proved that miR-124
      inhibits the proliferation and migration of HCC at least partly through targeting
      BIRC3 and regulating NF-kappaB signaling pathway, and it may be a therapeutic
      target for HCC prognosis.

PMID- 30210623
TI  - Identification of Genes and Pathways Involved in Ovarian Epithelial Cancer by
      Bioinformatics Analysis.
AB  - Ovarian epithelial cancer (OEC) is an often fatal disease with poor prognosis in
      women with high-stage disease. In contrast, ovarian low malignant potential (LMP)
      tumors with favorable prognosis behaves as a disease between benign and malignant
      tumors. The involved genes and pathways between benign-like LMP and aggressive
      OEC are largely unknown. This study integrated two cohorts profile datasets to
      investigate the potential key candidate genes and pathways associated with OEC.
      Gene expression in two datasets (GSE9891 and GSE12172), including 327 OECs and 48
      LMP tumors, were analyzed. 559 differentially expressed genes were found to
      overlap, 251 up-regulated and 308 down-regulated. Subsequently, analysis of gene
      ontology, signaling pathway enrichment and protein-protein interaction (PPI)
      network was performed. Gene ontology analysis clustered the up-regulated and down
      regulated genes based on significant enrichment. 282 nodes/ differentially
      expressed genes (DEGs) were identified from DEGs PPI network complex, and two
      most significant k-clique modules were identified from PPI. In a summary, using
      integrated bioinformatics analysis, we are able to identify biomarkers
      potentially significant in the pathogenesis of OEC, which can improve our
      understanding of the cause and molecular events. These candidate genes and
      pathways could be used for further confirmation, and lead to better disease
      diagnose and therapy.

PMID- 30210625
TI  - NCOA4-RET fusion in colorectal cancer: Therapeutic challenge using patient
      derived tumor cell lines.
AB  - The RET fusion is considered as the potential novel target in solid tumors.
      However, RET fusion is not well yet identified in colorectal cancer (CRC), and
      the effect of RET kinase inhibitor is also not evaluated in CRC with RET fusion.
      We established patient-derived tumor cells (PDCs) with RET fusion from recurrent
      brain metastatic lesion that newly appeared during the surveillance for stage III
      CRC patient. To investigate therapeutic options to CRC patient with a RET fusion,
      we performed cell viability assays using the PDCs. NCOA4-RET fusion was detected
      by FusionPlex using the resected brain metastatic tissue of CRC patient with
      solitary brain metastasis and then reconfirmed by fluorescence in situ
      hybridization (FISH) test. We also confirmed the RET fusions by a qPCR in matched
      PDCs. We tested whether the PDCs from RET fusion colon cancer were sensitive to
      carbozantinib, sorafenib, vandetanib, and PD0331992. Cell viability assays showed
      that carbozantinib, sorafenib, and PD0332991 did not suppress cell viability.
      Only, vandetanib revealed the significant inhibitory effect in MTT proliferation
      assay. Next, we analyzed regulation of targeted downstream pathways upon exposure
      to vandetanib by immunoblot assay. In colon cancer PDCs with NCOA4-RET fusion,
      vandetanib potently inhibited AKT and ERK phosphorylation. This study shows that
      vandetanib might be one of useful treatment strategies for CRC patient with NCOA4
      RET fusion. Therefore, inhibition of the RET kinase is a promising targeted
      therapy for cancer patients whose tumors harbor a RET rearrangement.

PMID- 30210624
TI  - Concurrent Chemoradiotherapy versus Intensity-modulated Radiotherapy Alone for
      Elderly Nasopharyngeal Carcinoma Patients with Pre-treatment Epstein-Barr Virus
      DNA: A Cohort Study in an Endemic Area with Long-term Follow-up.
AB  - Purpose: To date, no guidelines exist for elderly nasopharyngeal carcinoma (NPC)
      patients (60 years of age or older) due to a lack of prospective clinical trials.
      This study evaluated the efficacy of concurrent chemotherapy (CCRT) for NPC in
      elderly patients treated with intensity-modulated radiotherapy (IMRT). Methods:
      Patients were identified from a prospectively maintained database. A total of 198
      consecutive cases of elderly patients with NPC receiving IMRT, including 103
      patients treated with IMRT plus CCRT and 95 patients treated with IMRT alone,
      were analysed from January 2002 to December 2013. Multivariate analysis (MVA)
      using the Cox proportional hazards model and propensity score analysis (PSA) were
      performed for overall survival (OS) and disease-free survival (DFS). Finally,
      sensitivity analysis was performed. Results: The median follow-up time was 55.3
      months (range, 3-135.6 months). In the entire cohort, both MVA and PSA models
      showed that compared with IMRT alone, IMRT plus CCRT significantly improved
      survival (hazard ratio [HR] 2.143, 95% confidence interval [95% CI] 1.180-3.890;
      HR 1.961, 95% CI, 1.117-3.443, for OS and DFS, respectively). Similar results
      were found in the subgroups with high levels of Epstein-Barr virus (EBV) DNA,
      except in the low-EBV-DNA cohort. The total rates of severe acute toxicity,
      including leukopenia, neutropenia, stomatitis, and emesis, were significantly
      higher in the IMRT+CCRT group than in the IMRT-alone group (P < 0.001) but were
      similar to the rates of severe late toxicity (P = 0.818). Sensitivity analysis
      confirmed the robustness of our analysis. Conclusions: In the era of IMRT, CCRT
      retained survival benefits at high EBV DNA levels but not at low EBV DNA levels
      for elderly NPC patients. Randomized clinical trials are needed to confirm our
      findings.

PMID- 30210626
TI  - The cost of hospital treatment of advanced stage lung cancer patients in a
      developing South East European country.
AB  - Assessing the lung cancer treatment costs is necessary in order to estimate the
      budget impact of new interventions and therapeutic innovations. However, there
      are few studies regarding the use of resources and costs associated with
      treatment of lung cancer patients, not only in Serbia, but internationally. The
      aim of this paper was to assess the hospital costs of diagnosing and treating
      patients with stage IIIB and IV non-small cell lung cancer. Analysis of costs of
      care, services, medications and medical supplies, as well as of total hospital
      costs, was performed. Patients diagnosed with stage IIIB or IV NSCLC in the
      Institute during the year 2013 were enrolled in the study. A total of 187
      patients with stage IIIB or IV NSCLC were analyzed. Total hospital costs were
      506.970?, of which nearly two thirds was accounted to costs of services and
      medications. The mean cost per patient with adenocarcinoma was 3.075?, and for
      squamous cell lung carcinoma patient 1.943?. Statistically significant difference
      was shown when comparing mean hospital costs between patients in stage IIIB and
      stage IV adenocarcinoma, where this cost is higher in patients with stage IIIB.
      Mean hospital cost per female patient was nearly double as high that of the male
      patients, although without statistically significant difference. The mean cost
      for all adenocarcinoma patients was 1.317?, and for only four patients treated
      with TKI therapy 21.233?. This cost analysis could provide useful information in
      terms of budget impact of different lung cancer treatments and innovations in
      Serbia and corresponding developing countries.

PMID- 30210627
TI  - Lung Cancer and Pulmonary Embolism: What Is the Relationship? A Review.
AB  - Pulmonary embolism (PE) is gradually considered to be the third most common
      disease in the vascular disease category. Lung cancer is the most frequently
      diagnosed cancer and the leading cause of cancer death among males worldwide.
      Although initially appearing as distinct entities, lung cancer is a great risk
      factor for the development of PE. Pulmonary embolism is common in lung cancer
      patients, with a pooled incidence of 3.7%, and unsuspected pulmonary embolism
      (UPE) is also non-negligible with a rough rate ranging from 29.4% to 63%. Many
      risk factors of PE have been detected and could be classified into three
      categories: lung cancer-related, patient-related, and treatment-related factors.
      Decreased mean survival time could be significantly observed in lung cancer
      patients with PE or UPE compared to those only, but suspected PE has higher
      mortality than UPE. Prophylactic anticoagulant therapy benefit might be highest
      in patients with stage IV non-small cell lung cancer (NSCLC) or limited small
      cell lung cancer (SCLC), and heparin seems superior to warfarin for thrombotic
      prophylaxis. Periodically reassessing the risk-benefit ratio of anticoagulant
      treatment will be an efficient treatment strategy in lung cancer patients with
      PE.

PMID- 30210629
TI  - NKX2-2 Suppresses Osteosarcoma Metastasis and Proliferation by Downregulating
      Multiple Target Genes.
AB  - Osteosarcoma is the most common primary malignant bone tumor. However, our
      understanding of the molecular mechanism underlying its pathogenesis is
      incomplete. Studies have shown that aberrant expression of NK homeobox (NKX)
      genes may be involved in the oncogenesis of various cancers. Here, through
      migration screening assay, we found that a series of NKX genes inhibit the
      migration of osteosarcoma cells. Among these genes, NKX2-2 is a bona fide tumor
      suppressor for osteosarcoma. Overexpression of NKX2-2 decreases the migration,
      invasion, proliferation and colony formation of osteosarcoma cells in vitro and
      suppresses tumor growth and metastasis in vivo. Moreover, based on the results
      from both in vitro and in vivo studies, the transcriptional activation domain of
      NKX2-2 is important for its tumor suppressor function. Mechanistically, we
      revealed that NKX2-2 acts as a tumor suppressor partially by mediating the
      transcriptional downregulation of COL5A2, PLAU, SEMA7A and S1PR1 genes. In
      summary, our studies of NKX2-2 revealed new molecular mechanisms underlying
      osteosarcoma proliferation and metastasis and may provide a series of potential
      therapeutic targets for osteosarcoma.

PMID- 30210628
TI  - Risk Assessment and Hydrodissection Technique for Radiofrequency Ablation of
      Thyroid Benign Nodules.
AB  - Purpose: This retrospective study aimed to explore the importance of risk
      assessment and hydrodissection pre-treatment for radiofrequency ablation of
      thyroid nodules and initially establish the concept of thyroid nodule risk
      assessment and the corresponding ablation norms. Method: Based on the specific
      location of thyroid nodules, risk assessment and the corresponding preventive
      measures for thyroid ablation were established. During the period of 2015.10
      2017.5, a total of 382 patients were enrolled to compare the safety and efficacy
      of the ablation for patients with or without risk assessment and the
      corresponding preventive measures. Statistical analysis encompassed Independent T
      test for continuous variables and Fisher's exact test/Chi-square test for
      categorical variables. Result: Of all 382 patients, 188 patients underwent
      ablation with risk assessment and the corresponding preventive measures before
      ablation and 194 without, respectively. The patient characteristics, risk
      grading, ablation time, thyroid function after ablation and the complete ablation
      rate showed no statistical differences exsisted between two groups (P>0.05). The
      complication in very high risk nodules was avoided in the group of patients with
      risk assessment and preventive measures before ablation. Conclusion: It is a very
      safe and effective way to carry out radiofrequency ablation after pre-treatment
      of thyroid nodules by hydrodissection technique according to risk assessment. It
      will provide clinicians with greater help in the ablation treatment of thyroid
      nodules, and improve the safety of the thyroid ablation.

PMID- 30210630
TI  - Genetic polymorphisms may influence the vertical growth rate of melanoma.
AB  - Background: Identification of new predictive markers in melanoma is of great
      clinical importance. This study was aimed to analyze association between selected
      common variants in the cancer susceptibility genes and melanoma progression at
      the time of diagnosis. Material and Method: The study included 243 consecutive
      patients with melanoma. Genotyping was performed using real-time PCR. Results:
      Our data revealed modest association between xeroderma pigmentosum
      complementation group D (XPD) codon 312 polymorphism and tumor thickness (as
      defined by Breslow score; XPD D312N CC: 3.00 +/- 3.78mm, CT: 1.71 +/- 2.48mm, TT:
      2,53 +/- 3,24mm, P=0.023). The CT genotype in XPD D312N polymorphism was more
      frequently represented in non-invasive melanomas compared to deeply penetrating
      tumors. None of the common SNPs in cyclin dependent kinase inhibitor 2A (CDKN2A),
      vitamin D receptor (VDR), melanocortin 1 receptor (MC1R) were associated with
      Breslow depth. Conclusion: These findings suggest that genetic alteration in XPD
      contributes to melanoma progression and may be a potential diagnostic and
      molecular prognostic marker.

PMID- 30210632
TI  - Systemic neutrophil lymphocyte ratio and mismatch repair status in colorectal
      cancer patients: correlation and prognostic value.
AB  - Purpose: Mismatch repair-deficient (dMMR) colorectal cancer (CRC) is associated
      with increased local immune response as compared with mismatch repair-proficient
      (pMMR) CRC. We evaluated the relationship between MMR status and systemic
      inflammatory factors, including neutrophil lymphocyte ratio (NLR) and C-reactive
      protein (CRP). We also assessed the prognostic value of these parameters. Methods
      and materials: We analysed the relationship between MMR status (obtained by
      histochemical analysis), neutrophil and lymphocyte counts, NLR, and CRP level.
      The impact of systemic inflammatory factors on survival was also evaluated in
      dMMR and pMMR CRC patients. Results: A total of 1353 male and 892 female patients
      were eligible for analysis, of which, 253 patients (11.3%) were found to have
      dMMR status. Patients with dMMR status presented with increased neutrophil
      counts, and higher NLR and CRP levels in early stage CRC. In stage IV CRC
      patients, no correlation between MMR status and systemic inflammatory factors was
      found. Lymphocyte counts did not correlate with MMR status. High NLR was a
      prognostic factor for poor survival in pMMR CRC. However, NLR was not a
      prognostic factor in dMMR CRC. Conclusions: Our results suggest that dMMR CRC
      correlates with higher neutrophil count, NLR and CRP levels only in non
      metastatic patients, and NLR has prognostic value only in pMMR CRC.

PMID- 30210633
TI  - Clinical Value of Combining 18F-FDG PET/CT and Routine Serum Tumor Markers in The
      Early Detection of Recurrence Among Follow-up Patients Treated for Cervical
      Squamous Cell Carcinoma.
AB  - Objective: The purpose of this retrospective study was to investigate the role of
      18F-Fluorodeoxyglucose Positron Emission Tomography (18F-FDG PET/CT) and evaluate
      if combined elevated serum tumor markers levels improve the accuracy of 18F-FDG
      PET/CT in detecting recurrence of cervical squamous cell carcinoma. Methods: A
      total number of 42 patients who were treated for cervical squamous cell carcinoma
      and had underwent 18F-FDG PET/CT for suspected recurrence of cervical cancer were
      retrospectively reviewed in this study and their clinical, pathological and
      serological data were collected and analyzed. The clinical value of combining 18F
      FDG PET/CT with serum tumor markers was investigated. Results: Among the 42
      patients, 18F-FDG PET/CT was true positive in 25 (59.5%), false positive in 5
      (11.9%), true negative in 12 (28.5%) and false negative in none. The overall
      patient-based sensitivity, specificity, accuracy, positive predictive value and
      negative predictive value of 18F-FDG PET/CT in detecting recurrent cervical
      cancer were 100%, 70.6, 88.1%, 83.3%, and 100%, respectively. The accuracy of 18F
      FDG PET/CT with combined squamous cell carcinoma antigen (SCC Ag) and
      carcinoembryonic antigen (CEA) elevation was 100% compared to only SCC Ag
      elevation and only CEA elevation, 90% and 33.3%, respectively. The positive
      predictive value of a positive 18F-FDG PET/CT with combined SCC Ag and CEA
      elevation was 100% for detection of recurrent cervical cancer. Also, the negative
      predictive value of a negative 18F-FDG PET/CT combined with normal SCC Ag and CEA
      levels was 100%. Conclusion:18F-FDG PET/CT is highly sensitive in the diagnosis
      of recurrent cervical cancer. When 18F-FDG PET/CT is associated with both SCC Ag
      and CEA elevation or only SCC Ag elevation, the accuracy is increased but not
      when associated with only CEA elevation. Positive 18F-FDG PET/CT associated with
      both tumor markers elevation can precisely predict recurrence. Moreover, normal
      levels of both tumor markers with a negative 18F-FDG PET/CT result may clinically
      reassure that a recurrence is absent.

PMID- 30210631
TI  - Exosome-related tumor microenvironment.
AB  - The tumor microenvironment (tumor cells are located in the internal and external
      environment) is vital for the occurrence, growth and metastasis of tumors. An
      increasing number of studies have shown that exosomes are closely related to the
      tumor microenvironment. The mechanisms involved, however, are unclear. The focus
      of this review is on the exosome-related tumor microenvironment and other
      relevant factors, such as hypoxia, inflammation and angiogenesis. Many studies
      have suggested that exosomes are important mediators of metastasis, angiogenesis,
      and immune modulation in the tumor microenvironment. Additionally, exosomes can
      be isolated from bodily fluids of cancer patients, including urine, blood,
      saliva, milk, tumor effusion, cerebrospinal fluid, amniotic fluid and so on.
      Consequently, exosomes are potential biomarkers for clinical predictions and are
      also good drug carriers because they can cross the biofilm without triggering an
      immune response. Collectively, these findings illustrate that exosomes are
      crucial for developing potential targets for a new generation of pharmaceutical
      therapies that would improve the tumor microenvironment.

PMID- 30210634
TI  - The relationship between miR-302b and EphA2 and their clinical significance in
      gastric cancer.
AB  - Introduction: EphA2 is a crucial oncogene in gastric cancer (GC) development and
      metastasis, and miR-302b can target EphA2 in gastric cancer. This study plans to
      investigate their relationship and clinical significance in clinical samples.
      Materials and Methods: We explored the correlation of the expression of EphA2 and
      miR-302b, and their clinical significance in the training (n=226) cohort of GC
      patients, and then validated the results in the validation (n=128) cohort.
      Results: miR-302b was remarkably downregulated in GC tissues, while high EphA2
      expression were detected, and they were inversely correlated both in mRNA and
      protein, (r=-0.4209, P<0.0001; r=-0.336, P <0.001, respectively). Furthermore,
      the pattern of high EphA2 and low miR-302b expression were found to be associated
      with poor overall survival in stage IV GC patients in both training and
      validation cohort. Conclusions: The expression of miR-302b and EphA2 was
      inversely correlated, and had prognostic significance on GC in clinic.

PMID- 30210635
TI  - Preoperative CEA levels are supplementary to CA19-9 levels in predicting
      prognosis in patients with resectable intrahepatic cholangiocarcinoma.
AB  - Background: There are few diagnostic tools that can be used to determine which
      patient with intrahepatic cholangiocarcinoma (ICC) can benefit from surgery
      actually, highlighting that the need for new preoperative stratification
      strategies. The aim of this study was to investigate the predictive values of
      preoperative biomarkers in survival analyses for patients with ICC after surgical
      resection. Methods: A total of 285 patients with ICC were retrospectively
      reviewed. Receiver operating charateristics (ROC) curves were used to evaluate
      the predictive effects of preoperative carbohydrate antigen 19-9 (CA19-9) with
      different cutoff values and carcinoembryonic antigen (CEA) in patients with ICC.
      Results: Preoperative CA19-9 with a cutoff value of 200 U/ml performed better in
      predicting overall survival (OS) and progression free survival (PFS) in ICC
      patients. Patients with preoperative CA19-9 value > 200 U/ml generally had a poor
      surgical response. However, surgical resection could also benefit patients whose
      CA19-9 levels decreased postoperatively or preoperative CEA levels were negative.
      Conclusions: With the cutoff value of 200U/ml, CA19-9 was a better preoperative
      biomarker for predicting survival for ICC patients after surgical resection.
      Combination of preoperative CA19-9 and CEA showed the strongest predictive power
      in survival analyses in these patients and should be recognized in daily clinical
      care.

PMID- 30210636
TI  - Mesenchymal Stem Cell Derived Exosomes in Cancer Progression, Metastasis and Drug
      Delivery: A Comprehensive Review.
AB  - With the development of cancer treatments, it has become a popular research focus
      that mesenchymal stem (or stromal) cells (MSCs) have the functional mechanisms
      that influence cancer progression. One of the underestimated mechanisms is
      secretion of highly specialized double-membrane structures called exosomes.
      Mesenchymal stem cells generate several exosomes that may act as paracrine
      mediators by exchanging genetic information. MSC-derived exosomes are
      microvesicles ranging from approximately 60-200 nm in size and detected in
      various body fluids. It has been demonstrated that MSC-derived exosomes are
      involved in tumor growth, angiogenesis, metastasis, and invasion. Furthermore,
      emerging evidence suggests that as natural nanocarriers, MSC-exosomes are
      responsible for multidrug resistance mechanisms, reverse effect of radiation
      injury, and immune regulation, which can be used in clinical applications for
      cancer therapy. The present review aims to briefly describe the properties and
      biological functions of MSC-exosomes in cancer progression and its possible
      clinical applications in the future.

PMID- 30210637
TI  - Role of CXCR7 as a Common Predictor for Prognosis in Solid Tumors: a Meta
      Analysis.
AB  - Background: Accumulating evidence indicated that the CXC chemokine receptor
      (CXCR) 7 (CXCR7) was overexpressed in a variety of tumors. However, the value of
      the CXCR7 expression in predicting prognosis in solid tumors remains
      controversial. Therefore, we performed this meta-analysis to evaluate the
      correlation between CXCR7 expression and lymph node metastasis (LNM), tumor
      pathological grade and survival, including overall survival (OS), disease-free
      survival (DFS) and recurrence-free survival (RFS). Methods: Eligible studies were
      searched in PubMed, Web of Science, and PMC up to April 2018. A total of 27
      studies were included in this meta-analysis. Odds ratio (OR), hazard ratio (HR)
      and 95 % confidence intervals (CI) were used as effect measures. Results: The
      meta-analysis showed that high expression of CXCR7 predicted a high risk of LNM
      (pooled OR = 2.22, 95%CI: 1.41-3.50), high tumor grade (pooled OR = 1.94, 95%CI:
      1.20-3.13), poor OS (pooled HR = 1.66, 95%CI: 1.30-2.03), and poor DFS/RFS
      (pooled HR = 1.82, 95%CI: 1.21-2.43). Subgroup analysis showed that CXCR7
      expression had a positive correlation with LNM in pan-adenocarcinoma subgroup
      (pooled OR = 3.73, 95%CI: 2.21-6.30), while no correlation was found in pan
      squamous cancer subgroup (pooled OR = 1.29, 95%CI: 0.56-2.96). Subgroup analysis
      of tumor grade revealed that high expression of CXCR7 predicted high tumor grade
      both in pan-squamous cancer and pan-adenocarcinoma (pooled OR = 3.58, 95%CI: 1.39
      9.22, pooled OR = 2.25, 95%CI: 1.20-4.20). As in OS group, we divided the data
      based on analysis method and it turned out that overexpressed CXCR7 predicted
      worse OS both in multivariate analysis (pooled HR =1.57, 95%CI: 1.12-2.01) and
      univariate analysis subgroup (pooled HR =1.86, 95%CI: 1.23-2.49). Conclusions:
      Our meta-analysis revealed that high expression of CXCR7 predicted unfavorable
      prognosis and may serve as potential targets of cancer therapy.

PMID- 30210639
TI  - Overall survival and cancer-specific survival in patients with surgically
      resected pancreatic head adenocarcinoma: A competing risk nomogram analysis.
AB  - Background: The objective of this study was to estimate probabilities of overall
      survival (OS) and cancer-specific survival (CSS) in patients with pancreatic head
      adenocarcinoma after surgery. In addition, we attempted to build nomograms to
      predict prognosis of these patients. Methods: Patients diagnosed with surgically
      resected pancreatic head adenocarcinoma between 2004 and 2014 were selected for
      the study from the Surveillance, Epidemiology, and End Results (SEER) database.
      Nomograms were established for estimating 1-, 2- and 3-year OS and CSS based on
      Cox regression model and Fine and Grey's model. The performance of the nomogram
      was measured by concordance index (C-index) and the area under receiver operating
      characteristic (ROC) curve (AUC). Results: A total of 2374 patients were
      retrospectively collected from the SEER database. The discrimination of nomogram
      for OS prediction was superior to that of the Tumor-Node-Metastasis (TNM) 7th or
      8th edition stage systems (C-index = 0.640, 95% CI, 0.618 - 0.662 vs 0.573, 95%
      CI, 0.554 - 0.593, P < 0.001; 0.640, 95% CI, 0.618 - 0.662 vs 0.596, 95% CI,
      0.586 - 0.607, P < 0.001, respectively). The comparisons of values of AUC showed
      that the established nomograms displayed better discrimination power than TNM 7th
      or 8th stage systems for predicting both OS and CSS. Conclusions: The nomograms
      which could predict 1-, 2- and 3-year OS and CSS were established in this study.
      Our nomograms showed a relatively good performance and could be served as an
      effective tool for prognostic evaluation of patients with pancreatic head
      adenocarcinoma after surgery.

PMID- 30210638
TI  - Covalent CDK7 Inhibitor THZ1 Inhibits Myogenic Differentiation.
AB  - Covalent CDK7 inhibitor THZ1 is a newly discovered anti-tumor drug.THZ1 affects
      the function of transcription factor TFIIH by inhibiting CDK7, which in turn
      affects RNA polymerase II, and ultimately affects transcription initiation. Study
      found that THZ1 could inhibit proliferation and promote apoptosis of several
      tumor cell lines. However, there is no report of the potential side effect of
      THZ1 in normal tissues. In the course of cancer, the muscle consumption of
      cachexia needs to be supplemented by the differentiation of muscle cells.
      However, the effect of THZ1 on myogenic differentiation remains unclear. Our
      study in this article found that THZ1 could both inhibit the differentiation of
      C2C12 cells and mouse primary myoblasts, also repressing the expression of
      differentiation-related transcription factors and muscle structural proteins,
      such as and myogenin, myh3 and MCK. Moreover, THZ1 could inhibit C2C12 cell
      proliferation and migration, increase its oxidative stress and promote its
      apoptosis. Our data indicates that THZ1 inhibits myogenic differentiation,
      suggesting that therapies based on THZ1 might have potential side effects on
      muscle functions.

PMID- 30210640
TI  - Significantly higher pathologic complete response (pCR) after the concurrent use
      of trastuzumab and anthracycline-based neoadjuvant chemotherapy for HER2-positive
      breast cancer: Evidence from a meta-analysis of randomized controlled trials.
AB  - Objectives: To investigate the effect of the concurrent use of trastuzumab and
      anthracycline-based neoadjuvant chemotherapy (NAC) for HER2-positive breast
      cancer in terms of pCR and cardiotoxicity. Methods: We systematically searched
      Pubmed, Embase, Cochrane and SinoMed databases from inception until 1 July 2017
      for relevant articles of randomized controlled studies. After identified all
      relevant studies that reported the concurrent use of trastuzumab and
      anthracycline-based NAC for HER2-positive locally advanced breast cancer, five
      eligible randomized studies were extracted relevant data and assessed for design
      and quality, and the meta-analysis was conducted to evaluate the risk ratio (RR)
      of pCR and other interesting outcomes, such as left ventricular ejection fraction
      (LVEF) decrease more than 10%, responses, recurrence free survival (RFS) and
      overall survival (OS). Results: A total of five randomized controlled studies
      were included in the meta-analysis, including 232 HER2-positive locally advanced
      breast cancer patients received the concurrent use of trastuzumab and
      anthracycline-based NAC. The results showed that the pCR rate was significantly
      higher in the group received the concurrent use of trastuzumab and anthracycline
      based NAC (48%) than that in the non-concurrent use of trastuzumab and
      anthracycline-based NAC group (26%) (RR: 1.76, 95%CI: 1.37-2.26, p<0.0001).
      Besides, higher rate of RFS (RR: 1.14, 95%CI: 1.03-1.26, p=0.009) was observed in
      the concurrent use of trastuzumab and anthracycline-based NAC group. No
      significant differences in LVEF decreased more than 10% (p=0.50) between both
      groups. Conclusions: Our meta-analysis of randomized controlled studies showed
      that pCR rates are significantly higher in the concurrent use of trastuzumab and
      anthracycline-based NAC compared with the non-concurrent use of trastuzumab and
      anthracycline-based NAC for certain HER2-positive breast cancer, meanwhile
      without significant increase of the cardiotoxicity.

PMID- 30210641
TI  - Alternative Splicing of SMAD4 and Its Function in HaCaT Cells in Response to UVB
      Irradiation.
AB  - Alternative splicing is one of the most common mechanisms of human gene
      regulation and plays a crucial role in increasing the diversity of functional
      proteins. Many diseases are linked to alternative splicing, especially cancer.
      SMAD4 is a member of the SMAD family and plays a critical role in mediating of
      TGF-beta signal transduction and gene regulatory events. Smad4 is a tumour
      suppressor and acts as a shuttling protein between nucleus and cytoplasm. The
      splicing variants of Smad4 have been found in many cancers. The present study
      performed nested PCR to detect alternative splicing of Smad4 in HaCaT cells lines
      in response to UVB irradiation. The UVB induced a novel Smad4B isoform that led
      to decrease the Smad4 expression. The hnRNPA1 splicing factor is responsible for
      Smad4 alternative splicing in response to UVB. The UVB increased the expression
      of SF2 and hnRNPA1 Splicing factors. The hnRNPA1 overexpression induced Smad4B by
      regulating Smad4 alternative splicing. The Smad4B isoform supported the function
      of Smad4 full length in UVB resistance with certain limitation. The western blot
      analyses showed that the overexpressed Smad4 full length significantly increased
      N-cadherin expression while Smad4B overexpression decreased the expression the N
      cadherin (P<0.05). Furthermore, overexpression of the isoform in HaCaT cells
      decreased cell invasion as compared to Smad4 full-length overexpression. These
      results will be helpful to understand the importance of Smad4 alternative
      splicing in skin tumorigenesis.

PMID- 30210643
TI  - Inhibition of Transient Receptor Potential Vanilloid 6 channel, elevated in human
      ovarian cancers, reduces tumour growth in a xenograft model.
AB  - Background: Transient Receptor Potential Vanilloid 6 (TRPV6), a non-voltage gated
      calcium channel, is implicated in malignancies and correlates with Gleason scores
      in prostate cancer and with poor prognosis in breast cancer. Data on the TRPV6
      status of ovarian malignancies has not received significant attention. The effect
      of inhibiting TRPV6 activity on ovarian tumour growth has never been reported.
      Methods: We quantified TRPV6 mRNA and protein in biopsies of five types of
      ovarian cancer at different stages and grades by quantitative PCR and
      immunohistochemistry respectively. We verified the presence of TRPV6 in SKOV-3
      cells and xenografts by Western Blotting. NOD/SCID mice bearing xenografted
      ovarian tumours derived from SKOV-3 were treated daily with TRPV6-antagonistic
      peptides (SOR-C13 and SOR-C27) at 400, 600 and 800 mg/kg delivered
      intraperitoneally (i.p.) over 12 days. Data from qPCR and tumour growth
      experiments were compared with a Student's t-test. Immunohistochemical ranking of
      staining were compared with Kruskall-Wallace one-way ANOVA and Dunn's Multiple
      Comparison post-test. Results: TRPV6 mRNA and protein are significantly elevated
      at all stages and grades of 5 ovarian cancer types over normal tissue. Overall
      qPCR log2 values (n, mean, +/- SEM) for mRNA in tumour (n = 165, 5.06 +/- 0.16)
      were greater (p < 0.05) than normal tissues (n = 26, 0.45 +/- 0.41). All stages
      and grades included in the biopsy arrays were significantly greater than normal
      tissues. Immunohistochemical staining of TRPV6 was ranked >2 (faint in most
      cells) in 80.5% of tumours (123) while 92% of normal tissues (23) ranked <= 2.
      Daily i.p. injection with SOR-C13 (400, 600 and 800 mg/kg) over 12 days inhibits
      tumour growth (59%) at the highest dose compared to non-treated controls. SOR-C27
      at 800 mg/kg SOR-C27 inhibited tumour growth 55% after 12 days. Results of daily
      and intermittent dosing (Days 1, 2, 3 and 8, 9, 10) with SOR-C13 were
      indistinguishable. Conclusion: TRPV6 mRNA and protein are elevated in biopsies of
      ovarian cancers compared to normal tissue. Inhibition of TRPV6 activity
      significantly reduces ovarian tumour growth providing evidence that TRPV6 is a
      feasible oncology target in ovarian cancers.

PMID- 30210645
TI  - Role of a Community Pharmacy Service in Care of Bronchial Asthma Patients in
      Lithuania.
AB  - Bronchial asthma is one of the most common chronic respiratory diseases, and its
      care is often complex. In this research, we tested the proposal that
      participation of pharmacists in the management of bronchial asthma can improve
      patient outcomes. A two-stage study was constructed consisting of a training
      element and a service element, using the Asthma Control Test and a structured
      questionnaire about the patients' disease condition (based on the results of a
      qualitative study). The study was conducted in 21 pharmacies in Lithuania and
      involved 338 asthmatic patients (age 18-88 years). It was found that before the
      pharmacy service was provided, the average number of mistakes patients made in
      administration of asthma medications was 2.03; this number decreased to 1.12
      after the service was provided (p < 0.05). Disease control paralleled the
      improvement in number of mistakes: 26.1% of patients who previously exerted no
      control over the disease symptoms began to exert sufficient control over their
      asthma symptoms (Asthma Control Test >20) after the service was provided (p <
      0.05). The reduced number of mistakes probably can be attributed to the positive
      effects of the provided services. By reducing the number of patient mistakes,
      pharmacists may improve the outcomes of asthmatic patients.

PMID- 30210642
TI  - Study to evaluate the immunomodulatory effects of radiofrequency ablation
      compared to surgical resection for liver cancer.
AB  - Introduction: Hepatic cancer is a highly lethal tumour with increasing worldwide
      incidence. These tumours are characterized by the proliferation of malignant
      cells, generalised immunosuppression and chronic inflammation marked with an
      increase in inflammatory markers as a neutrophil-to-lymphocyte ratio (NLR), the
      platelet-to-lymphocyte ratio (PLR) and overexpression of CD4+CD39+ on T
      lymphocytes. The studies have outlined immunomodulatory changes in liver cancer
      patients as the plausible explanation for the better survival. The aim of this
      pilot study was understand the possible immunomodulatory effect of radiofrequency
      (RF) energy and liver resection (non-radiofrequency based devices; non-RF device)
      in relation to NLR, PLR and expression of CD4+CD39+ T lymphocytes and compare the
      magnitude of these changes. Material and Methods: In the present study, 17
      patients with hepatic cancer were prospectively divided into treatment groups
      radiofrequency ablation (RFA group) and Liver resection using non-RF devices (LR
      group). A blood sample was collected from each patient, one month before and
      after the procedure and compared with the blood samples of age-matched healthy
      volunteers for group wise comparison. The Mann-Whitney U test, Mc Nemar test and
      Wilcoxon rank test were used for statistical comparisons as appropriate. Results:
      A decrease in NLR was reported after RFA from 4.7+/-3.3 to 3.8+/-1.8 (P=0.283),
      in contrary to an increase from 3.5+/-2.8 to 4.5+/-3.2 (P=0.183) in LR group.
      Likewise, a decrease was discerned in PLR following RFA from 140.5+/-79.5 to
      137+/-69.2 respectively (P=0.386) and increase in the LR group from 116+/-42.2 to
      120.8+/-29 respectively (P=0.391). A significant decrease in CD4+CD39+
      lymphocytes from 55.8+/-13.8 to 24.6+/-21.1 (P=0.03) was observed in RFA group
      whilst a significant increase was reported in LR group from 47.6+/-8.8 to 55.7+/
      33.2 (P=0.38). Conclusion: Studies have shown that decrease in the NLR, PLR and
      expression of CD4+CD39+ on T lymphocytes as the marker of better survival in
      hepatic cancer patients and our findings have confirmed that these changes can be
      induced following application of RF energy. Moreover, this could be the
      explanation of better survival observed in different studies using RFA or other
      RF-based devices in comparison to non-RF based liver resection techniques.
      However, further larger studies are needed to confirm these findings.

PMID- 30210644
TI  - Validation of Urine-based Gene Classifiers for Detecting Bladder Cancer in a
      Chinese Study.
AB  - Background: Current standard methods used to detect and monitor bladder cancer
      (BC) are invasive or have low sensitivity. We have previously reported in an
      international European study four non-invasive tests for BC diagnosis based on
      the gene expression patterns of urine. Objective: to validate the tests in an
      independent Asian cohort. Design, setting and participants: Prospective blinded
      study in which consecutive voided urine samples from BC patients and controls
      (n=520) were collected in the Fudan University Shanghai Cancer Center from 2014
      2016. Gene expression values were quantified using TaqMan Arrays. The same cut
      off as previously reported for discrimination between tumours and controls was
      used in this validation study. Results and limitations: Finally, a total of 257
      tumour and 132 control urine samples were analysed. We found a high accuracy for
      the four gene classifiers in this independent Asian set, the classifiers composed
      of 5 and 10 genes achieved the best sensitivity (80.54% and 81.32%, respectively)
      maintaining a high specificity (91.67% and 85.61%, respectively). Sensitivity of
      5-gene (GS_D5) and 10-gene (GS_D10) expression classifiers in recurrent BC cases
      (78 and 79%, respectively) is comparable to that of primary BC cases (82%).
      Cytology and NMP22 identified 67% and 40%, respectively, of tumours that have
      been diagnosed with our tests. In addition, influence of each studied gene was
      analyzed and showed similar gene rank between Chinese and Caucasian population.
      Conclusions: Our study proves that our non-invasive diagnostic BC tests can be
      reproduced in independent cohorts and in an external laboratory. All the four
      gene classifiers have shown equal or superior performance to the current gold
      standard in the present and previously reported validation studies. Consequently,
      they may be taken for consideration as molecular tests applicable to clinical
      practice in the management of BC. Patient summary: Our gene classifiers achieve
      sensitivities up to 90% in HR NMIBC and MIBC patients, while this achievement is
      comparatively lower in LR NMIBC ones.

PMID- 30210646
TI  - Study of Clinical Characteristics and Cytokine Profiles of Asthmatic Children
      with Rhinovirus Infection during Acute Asthma Exacerbation at National Hospital
      of Pediatrics.
AB  - Background: In children with asthma, the viral infection of airways is usually a
      main cause of acute asthma exacerbation and hospitalization. However, few studies
      on clinical and biomolecular characteristics of asthmatic children in this field
      have been done, especially in emergent countries. Objective: This study described
      the clinical and biological characteristics of asthmatic children who had acute
      asthma exacerbation and rhinovirus (RV) infection. Methods: Children under 15
      years of age hospitalized for acute asthma exacerbation were included. They
      underwent clinical examination and peripheral blood analyses for the cytokine
      profile. The severity of acute asthma exacerbation was evaluated by Pediatric
      Asthma Score (PAS). Healthy children under 15 years of age were also invited in
      this study. Results: One hundred fifteen asthmatic children were included in this
      study. There were 18.2% of mild PAS, 37.4% of moderate PAS, and 44.4% of severe
      PSA. Among them, 63/115 (54.8%) asthmatic children had positive RV infection
      (RV+). The percentages of asthmatic children with RV+ had increased
      polymorphonuclear leucocytes were significantly higher than asthmatic children
      with RV-. There were no significant differences of the concentrations of non-Th2
      related cytokines in asthmatic children with RV- and RV+. The concentration of
      Th2-related cytokines (IL-5 and IL-13) in asthmatic children with RV+ was
      significantly higher than those with RV-. However, there was no significant
      difference for the cytokine profile between mild, moderate, and severe asthma.
      Conclusion: RV infection is a main cause of acute asthma exacerbation in children
      with asthma. The increase of Th2-related cytokines, especially IL-5 and IL-13, is
      a relevant biomarker for RV infection in asthmatic children with severe
      exacerbation.

PMID- 30210647
TI  - L-Leucine Templated Biomimetic Assembly of SnO2 Nanoparticles and Their Lithium
      Storage Properties.
AB  - SnO2 nanoparticles have been synthesized by a novel route of a sol-gel method
      assisted with biomimetic assembly using L-leucine as a biotemplate. The
      microstructure of as-prepared SnO2 nanoparticles was characterized by X-ray
      diffraction (XRD), scanning electron microscopy (SEM), Fourier transform infrared
      spectra (FT-IR), and Brunner-Emmet-Teller (BET) measurements. The results
      demonstrated that the growth of SnO2 could be regulated by L-leucine at a high
      calcination temperature. The electrochemical performance of SnO2 was also
      measured as anodes for lithium-ion battery. It is a guidance for the growth
      regulation of SnO2 at high temperature to obtain SnO2/C with nanosized SnO2
      coated by a graphitic carbon.

PMID- 30210648
TI  - Oxidative-Nitrative Stress and Poly (ADP-Ribose) Polymerase Activation 3 Years
      after Pregnancy.
AB  - Background: Oxidative-nitrative stress and poly (ADP-ribose) polymerase
      activation have been previously observed in healthy and gestational diabetic
      pregnancies, and they were also linked to the development of metabolic diseases.
      The aim of the present study was to examine these parameters and their
      correlation to known metabolic risk factors following healthy and gestational
      diabetic pregnancies. Methods: Fasting and 2 h postload plasma total peroxide
      level, protein tyrosine nitration, and poly (ADP-ribose) polymerase activation
      were measured in circulating leukocytes three years after delivery in women
      following healthy, "mild" (diet-treated) or "severe" (insulin-treated)
      gestational diabetic pregnancy during a standard 75 g OGTT. Nulliparous women and
      men served as control groups. Results: Fasting plasma total peroxide level was
      significantly elevated in women with previous pregnancy (B = 0.52 +/- 0.13; p <
      0.001), with further increase in women with insulin-treated gestational diabetes
      (B = 0.36 +/- 0.17; p < 0.05) (R2 = 0.419). Its level was independently related
      to previous pregnancy (B = 0.47 +/- 0.14; p < 0.01) and current CRP levels (B =
      0.06 +/- 0.02; p < 0.05) (R2 = 0.306). Conclusions: Elevated oxidative stress but
      not nitrative stress or poly (ADP-ribose) polymerase activation can be measured
      three years after pregnancy. The increased oxidative stress may reflect the cost
      of reproduction and possibly play a role in the increased metabolic risk observed
      in women with a history of severe gestational diabetes mellitus.

PMID- 30210649
TI  - Anti-Inflammatory and Antioxidant Actions of Methyl Jasmonate Are Associated with
      Metabolic Modifications in the Liver of Arthritic Rats.
AB  - Methyl jasmonate (MeJA) is a fatty acid-derived cyclopentanone which shares
      structural similarities with prostaglandins and has been under study as a
      promising anti-inflammatory agent. This study investigated the actions of MeJA on
      systemic inflammation and oxidative status in rats with adjuvant-induced
      arthritis, a model for rheumatoid arthritis. MeJA (75 to 300 mg.kg-1) was
      administrated orally during 18 days after arthritis induction with Freund's
      adjuvant. Articular and systemic inflammation was greatly increased in arthritic
      rats, likewise the oxidative stress in plasma and liver. The hepatic glucokinase
      activity and glycolysis were increased in arthritic rats. MeJA decreased most
      inflammatory parameters and abolished the increased protein carbonylation in
      plasma and liver, diminished the increased hepatic ROS content, and restored the
      hepatic GSH/GSSG ratio in arthritic rats. However, the MeJA treatment decreased
      the hepatic glucokinase activity and glycolysis and stimulated mitochondrial ROS
      production in healthy and arthritic rats. Oxygen uptake was increased by MeJA
      only in livers from treated arthritic rats. This action may bear relation to the
      increased activity of mitochondrial NADP+-dependent enzymes to provide reducing
      equivalents for the glutathione cycle. These beneficial effects, however, are
      associated with a decreased glucose flux through the glycolysis in the liver of
      arthritic and healthy rats.

PMID- 30210651
TI  - Corrigendum to "Low-Level Laser Irradiation Exerts Antiaggregative Effect on
      Human Platelets Independently on the Nitric Oxide Metabolism and Release of
      Platelet Activation Markers".
AB  - [This corrects the article DOI: 10.1155/2017/6201797.].

PMID- 30210650
TI  - Pu-erh Tea Ameliorates Atherosclerosis Associated with Promoting Macrophage
      Apoptosis by Reducing NF-kappaB Activation in ApoE Knockout Mice.
AB  - We explored whether pu-erh tea consumption ameliorates atherosclerosis and the
      possible mechanism for its effects in apolipoprotein E-deficient (ApoE-/-) mice.
      Our data showed that pu-erh tea consumption markedly reduced early fatty streak
      formation and the advanced fibrofatty plaque sizes. Additionally, the mean
      proportion of inflammatory macrophages in the plaque decreased, and the number of
      apoptotic macrophages increased significantly. NF-kappaB activity in peritoneal
      macrophages decreased by 75.6% compared to the controls, similar with the levels
      of IL-6, IL-12, and TNF-alpha expression. The tea extract increased the apoptosis
      of RAW264.7 cells by decreasing NF-kappaB activation and reducing the
      inflammatory cytokine expression. In conclusion, pu-erh tea ameliorates
      atherosclerosis progress by alleviating the chronic inflammatory state by
      reducing NF-kappaB activation and promoting macrophage apoptosis in
      atherosclerotic plaques.

PMID- 30210652
TI  - Propionibacterium acnes Induces Intervertebral Disc Degeneration by Promoting
      iNOS/NO and COX-2/PGE2 Activation via the ROS-Dependent NF-kappaB Pathway.
AB  - Accumulating evidence suggests that Propionibacterium acnes (P. acnes) is a novel
      pathogenic factor promoting intervertebral disc degeneration (IVDD). However, the
      underlying mechanisms by which P. acnes induces IVDD have been unclear. In this
      study, we quantified the severity of IVDD, as well as the expressions of
      inducible nitric oxide synthase (iNOS)/nitric oxide (NO) and cyclooxygenase (COX
      2)/prostaglandin (PGE2) in human intervertebral discs (IVDs) infected with P.
      acnes. Compared with P. acnes-negative IVDs, P. acnes-positive IVDs showed
      increased iNOS/NO and COX-2/PGE2 activity concomitant with more severe IVDD. In
      order to detect the potential correlation between iNOS/NO expression, COX-2/PGE2
      expression, and IVDD, we developed a P. acnes-induced IVDD rat model and found
      that the upregulation of iNOS/NO and COX-2/PGE2 was essential to the occurrence
      of P. acnes-induced IVDD. This finding was supported by the fact that the
      inhibition of iNOS/NO and COX-2/PGE2 activity ameliorated IVDD significantly, as
      evidenced by restored aggrecan and collagen II expression both in vivo and in
      vitro. Mechanistically, we found that P. acnes induced iNOS/NO and COX-2/PGE2
      expressions via a reactive oxygen species- (ROS-) dependent NF-kappaB cascade.
      Furthermore, NADPH oxidase participated in P. acnes-induced ROS, iNOS/NO, and COX
      2/PGE2 expressions. Overall, these findings further validated the involvement of
      P. acnes in the pathology of IVDD and provided evidence that P. acnes-induced
      iNOS/NO and COX-2/PGE2 activation via the ROS-dependent NF-kappaB pathway is
      likely responsible for the pathology of IVDD.

PMID- 30210655
TI  - Corrigendum to "Fibroblast Growth Factor-9 Activates c-Kit Progenitor Cells and
      Enhances Angiogenesis in the Infarcted Diabetic Heart".
AB  - [This corrects the article DOI: 10.1155/2016/5810908.].

PMID- 30210653
TI  - Polypharmacological Profiles Underlying the Antitumor Property of Salvia
      miltiorrhiza Root (Danshen) Interfering with NOX-Dependent Neutrophil
      Extracellular Traps.
AB  - Danshen, the dried root of Salvia miltiorrhiza, one of the most investigated
      medicinal plants with well-defined phytochemical constituents, has shown
      prominent clinical outcomes for antioxidant, anti-inflammatory, and anticoagulant
      activities to attain vascular protection and additional benefits for cancer
      therapy. More recently, activation of neutrophil and excessive formation of
      neutrophil extracellular traps (NETs) have been observed in pathological
      conditions of metastatic cancers; thus, we hypothesized that suppression of NETs
      could account for an essential cellular event underlying Danshen-mediated
      reduction of the incidence of metastasis. Using an experimental pulmonary
      metastases model of red fluorescent protein- (RFP-) labeled gastric cancer cells
      in combination with macroscopic ex vivo live-imaging system, our data indicated
      that Danshen impaired the fluorescent intensity and quantity of metastatic
      nodules. Moreover, Danshen could prevent neutrophil trafficking to the metastatic
      sites with decreased plasma levels of neutrophil elastase (NE) and procoagulant
      potential featured by fibrinogen. We further established phorbol 12-myristate 13
      acetate- (PMA-) induced NET formation of human neutrophils and screened
      representative active compounds derived from the hydrophilic and hydrophobic
      fractions of Danshen using qualitative and quantitative methods. As a result, we
      found that salvianolic acid B (Sal B) and 15,16-dihydrotanshinone I (DHT I)
      exhibited superior inhibitory activities on NET formation and significantly
      attenuated the levels of citrullinated histone H3 (citH3), a biomarker for NET
      formation. Multitarget biochemical assays demonstrated that Sal B and DHT I
      distinctly modulated the enzymatic cascade involved in NET formation. Sal B and
      DHT I could disrupt NET formation at the earlier stage by blocking the activities
      of myeloperoxidase (MPO) and NADPH oxidase (NOX), respectively. Lastly, combining
      treatment of Sal B and DHT I under subED50 doses displayed remarkable synergism
      effect on NET inhibition. Altogether, these data provide insight into how
      promiscuous compounds from herbal medicine can be effectively targeted NETs
      towards hematogenous metastasis of certain tumors.

PMID- 30210654
TI  - Evodiamine Attenuates P2X7-Mediated Inflammatory Injury of Human Umbilical Vein
      Endothelial Cells Exposed to High Free Fatty Acids.
AB  - Insulin resistance and type 2 diabetes mellitus (T2DM) are highly prevalent
      around the world. Elevated concentrations of free fatty acids (FFAs) are closely
      related to insulin resistance and T2DM. P2X7 receptor is an ion channel gated by
      ATP, which is implicated in various scenarios including immune response, pain,
      and inflammation. In this study, we have explored whether P2X7 receptor is
      involved in pathological changes in human umbilical vein endothelial cells
      (HUVECs) induced by high FFA treatment, and the potential beneficial effects of
      evodiamine. Evodiamine could effectively suppress the enhanced expression of P2X7
      receptor caused by high FFAs at both mRNA and protein levels. In addition, high
      FFA-induced cytotoxicity, the upregulated release of ATP, and production of
      reactive oxygen species (ROS) could be ameliorated by evodiamine in HUVECs.
      Evodiamine could also reverse the decreased NO formation and the increased
      adhesive events of immune cells at high FFAs. Moreover, evodiamine inhibited P2X7
      dependent TNF-alpha expression and ERK 1/2 phosphorylation due to high FFAs. All
      these results indicated that evodiamine could correct the upregulated expression
      of P2X7 receptor induced under high FFA condition in HUVECs, and consequently
      suppressed oxidative stress and inflammatory responses.

PMID- 30210656
TI  - Biotoxicological Analyses of Trimeroside from Baccharis trimera Using a Battery
      of In Vitro Test Systems.
AB  - The use in folk medicine of Baccharis trimera and recent studies on DNA damage by
      oxidative stress mechanisms have motivated this study. We investigated the
      biotoxicological effects of trimeroside from this plant. Aqueous extract from
      aerial parts of B. trimera was fractioned by flash chromatography for further
      isolation by thin-layer chromatography. The novel nor-monoterpene glycoside,
      trimeroside, and three flavonoids, cirsimaritin, luteolin and quercetin, were
      isolated. The genotoxic and mutagenic potential of trimeroside was determined by
      Salmonella/microsome (TA98 and TA100), comet assay, and cytokinesis-block
      micronucleus cytome assay (CBMN-cyt) in HepG2 cells. We also screened trimeroside
      into different human tumoral cell lines by sulforhodamine B (SRB) assay.
      Mutagenicity was detected in TA100 strain with metabolic activation. Genotoxic
      effects were not observed in HepG2 by comet assay. However, a decrease in the
      nuclear index division in the 2.0 mg.mL-1 concentration and an increase of
      nucleoplasmic bridges in the 1.5 mg.mL-1 concentration were detected by CBMN-cyt
      assay indicating cytotoxic and mutagenic effects. In SRB assay, trimeroside
      showed weak antiproliferative activity against the cell lines.

PMID- 30210658
TI  - Joseph J. Fins' Rights Come to Mind: Brain Injury, Ethics and the Struggle for
      Consciousness.
AB  - The book reflects Fins' role as co-director of the Consortium for the Advanced
      Study of Brain Injury at Weill Cornell Medicine and the Rockefeller University
      and his struggle to answer the kinds of questions that stand to shape how society
      treats people with brain injuries. What is the capacity of brains to recover?
      What are the mechanisms of that recovery? How do we know that our assessments are
      accurately describing what's going on in a patient's mind? And what does society
      morally owe these patients and families?

PMID- 30210657
TI  - The Brain's Emotional Development.
AB  - From our earliest days, the brain rapidly develops thinking, mobility, and
      communication skills. But not quite as quick to develop are the parts of the
      brain that regulate and process our emotions. New research is helping scientists
      learn about areas that are crucial to emotional development, and how our
      surroundings fit into the picture. The findings could have far-reaching
      implications for both parents and policy-makers.

PMID- 30210660
TI  - The First Neuroethics Meeting: Then and Now.
AB  - It wasn't until 2002 that more than 150 neuroscientists, bioethicists, doctors
      of psychiatry and psychology, philosophers, and professors of law and public
      policy came together to chart the boundaries, define the issues, and raise some
      of the ethical implications tied to advances in brain research. On the 15 th
      anniversary of the Neuroethics: Mapping the Field conference in San Francisco, we
      asked three of the original speakers to reflect on how far the neuroethics field
      has come in 15 years-and where the field may be going in the next 15. 

PMID- 30210659
TI  - Olfaction: Smell of Change in the Air.
AB  - Every whiff you take not only brings a cloud of chemicals swirling up your nose,
      but matters to your experience of taste as well as smell. Scientists studying
      smell have not only provided compelling evidence that it's more sophisticated
      than previously thought, but believe that the sense of smell impacts our mood and
      behavior and has the potential to detect and treat some neurological disorders.
      Compared to other senses, smell has long been underappreciated, writes our
      author, but that is now beginning to change.

PMID- 30210661
TI  - Alan Alda's If I Understood You, Would I Have This Look on My Face?: My
      Adventures in the Art and Science of Relating and Communicating.
AB  - A primary function of my role is asking top neuroscientists to write about the
      latest developments in their specialty areas for lay readers. If they agree to
      the assignment, I encourage them to use-whenever possible-conversational
      language, anecdotes, storytelling, and their own voice in communicating what are
      often complex and hard-to-explain topics. Another option might be to suggest they
      read Alan Alda's new book before they begin.

PMID- 30210662
TI  - The Illusion of the Perfect Brain Enhancer.
AB  - Many questions loom over transcranial direct current stimulation (tDCS), a non
      invasive form of neurostimulation in which constant, low current is delivered
      directly to areas of the brain using small electrodes. It was first established
      in neuroscience research in the 1950s and 60s, but has seen rapid growth,
      particularly in the last five years. Originally developed to help patients with
      brain injuries such as strokes, tDCS is now also used to enhance language and
      mathematical ability, attention span, problem solving, memory, coordination, and
      even gaming skills. The authors examine its potential and pitfalls.

PMID- 30210663
TI  - Microglia: The Brain's First Responders.
AB  - New knowledge about microglia is so fresh that it's not even in the textbooks
      yet. Microglia are cells that help guide brain development and serve as its
      immune system helpers by gobbling up diseased or damaged cells and discarding
      cellular debris. Our authors believe that microglia might hold the key to
      understanding not just normal brain development, but also what causes Alzheimer's
      disease, Huntington's disease, autism, schizophrenia, and other intractable brain
      disorders.

PMID- 30210665
TI  - Matthieu Ricard and Wolf Singer's Beyond the Self: Conversations between Buddhism
      and Neuroscience.
AB  - Buddhism shares with science the task of examining the mind empirically. But
      Buddhism has pursued, for two millennia, direct investigation of the mind through
      penetrating introspection. Neuroscience, on the other hand, relies on third
      person knowledge in the form of scientific observation. In the book that is the
      subject of this review, two friends, one a Buddhist monk trained as a molecular
      biologist, and the other, a distinguished neuroscientist, offer their
      perspectives on the mind, the self, consciousness, the unconscious, free will,
      epistemology, meditation, and neuroplasticity.

PMID- 30210664
TI  - Neuroimaging Advances for Depression.
AB  - Depression is one of the world's most prevalent mental health problems, with as
      many as 350 million sufferers worldwide and close to 20 million sufferers in the
      US. While neuroimaging applications for identifying various types of depression
      have made enormous strides in recent years, no findings have been sufficiently
      replicated or considered significant enough to warrant application in clinical
      settings. Our authors are well equipped to tell us what the future may bring.

PMID- 30210667
TI  - New advances in immunotherapy for non-small cell lung cancer.
AB  - Immunotherapy is one of the methods that can change the survival rate of patients
      with malignant tumors, in addition to surgery therapy, radiotherapy, chemotherapy
      and targeted therapy. Among various immunotherapy methods, immunoprecipitation
      inhibitors have been the most effective medications developed in recent years. At
      present, more in-depth studies have been conducted for two immune checkpoint
      inhibitor pathways, programmed cell death protein 1 (PD-1)/Programmed death
      ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), and a
      variety of medications for those above mentioned. The present study briefly
      reviews the results of clinical trials for relevant immune checkpoint inhibitors
      in lung cancer.

PMID- 30210666
TI  - The critical role of histone lysine demethylase KDM2B in cancer.
AB  - The discovery of histone demethylases has revealed the dynamic nature of the
      regulation of histone methylation. KDM2B is an important histone lysine
      demethylase that removes methyl from H3K36me2 and H3K4me3. It participates in
      many aspects of normal cellular processes such as cell senescence, cell
      differentiation and stem cell self-renewal. Recent studies also showed that KDM2B
      was overexpressed in various types of cancers. This review focuses primarily on
      the current knowledge of KDM2B and its function in cancer development.

PMID- 30210668
TI  - A comprehensive investigation using meta-analysis and bioinformatics on miR-34a
      5p expression and its potential role in head and neck squamous cell carcinoma.
AB  - HNSCC is the sixth most common cancer worldwide and is characterized as an
      aggressive, malignant tumor. MiR-34a-5p (miR-34a) expression has been strongly
      linked to HNSCC development. However, the exact target gene of miRNA-34a-as well
      as its biological and mechanistic pathways-are unclear. It is critical that the
      clinical value of HNSCC receive further study. We conducted a continuous
      variable, meta-analysis from data found in the cancer literature as well as that
      provided by the Cancer Genome Atlas (TCGA) to estimate miR-34a expression in
      HNSCC. Next, TCGA database, microarray, and MiRWalk were all used to predict the
      target gene of miR-34a in HNSCC. Then, Gene Ontology (GO) and Kyoto Encyclopedia
      of Genes and Genomes (KEGG) enrichment analyses were used to explore the
      underlying molecular mechanism of miR-34a in HNSCC. Finally, we used Spearman's
      analysis and survival curves to identify the roles of related target genes
      involved in significant pathways during the development of HNSCC. Expression
      levels of miR-34a in HNSCC were significant lower than those in normal tissues
      (P<0.05) and summary receiver operating characteristic (sROC) was 0.72. The
      collective results obtained from KEGG and GO indicated that miR-34a may be
      involved in the development of HNSCC via known cancer pathways, including the p53
      and/or PI3K-Akt signalling pathways. Our results suggested miR-34a has potential
      use as a novel, non-invasive and highly sensitive biomarker for diagnostic in
      HNSCC. Finally, it likely plays an essential role in the deterioration and
      ultimate tumorigenesis of HNSCC through determined cancer pathways.

PMID- 30210669
TI  - Identification of down-regulated microRNAs in thyroid cancer and their potential
      functions.
AB  - BACKGROUND: The mechanism of microRNAs (miRNAs) in thyroid cancer is still
      unclear. We identified miRNAs with differential expression in thyroid cancer
      versus normal tissues. METHODS: Microarray datasets were obtained from the GEO
      and ArrayExpress databases, and from publications found via PubMed, EMBASE, and
      Web of Science. Differentially expressed miRNAs were identified using the limma
      package, and their targets predicted using miRWalk. Gene Ontology (GO), Kyoto
      Encyclopedia of Genes and Genomes (KEGG), and protein-protein interaction (PPI)
      network analyses were performed using these target genes to explore potential
      carcinogenic mechanisms. Correlations between target gene and miRNA expression
      levels were examined. Changes in target protein expression were confirmed using
      data from The Human Protein Atlas and the Cancer Genome Atlas. RESULTS: We
      ultimately included five datasets, and further analyzed the four miRNAs that were
      down-regulated in at least four datasets (miR-7-2-3p, miR-138-5p, miR-144-5p, miR
      486-5p). Predicted targets were enriched in GO terms including extracellular
      matrix organization, cell surface, and receptor binding, and in KEGG cancer
      pathways. PPI analysis identified 10 hub genes as key potential targets of these
      miRNAs. The expression levels of eight target genes were negatively correlated
      with those of their respective miRNAs. Furthermore, eight predicted target genes
      in cancer-related pathways showed up-regulated protein and mRNA expression in
      thyroid cancer. CONCLUSION: Low miRNA expression in thyroid cancer might
      influence tumorigenesis via critical pathways. The genes identified here may act
      as a starting point for further investigation of the carcinogenic mechanisms of
      these miRNAs.

PMID- 30210670
TI  - Diagnostic utility of fluorogenic peptide-conjugated Au nanoparticle probe
      corroborated by rabbit model of mild cartilage injury and panel of osteoarthritic
      patients.
AB  - Using a rabbit model of early-stage osteoarthritis (OA) and a sampling patients
      with OA, we evaluated the diagnostic utility of a fluorogenic peptide-conjugated
      gold nanoparticle (AuNP) probe in detecting mild cartilage injury, based on the a
      disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS-4) enzyme.
      Synthesis of this fluorescent turn-on probe (or AU-probe) required conjugation of
      AuNPs with a fluorescein isothiocyanate (FITC)-modified ADAMTS-4-specific peptide
      (DVQEFRGVTAVIR). Synovial fluid samples were then collected from 48 adult rabbits
      and 100 patients for comparative testing (ADAMTS-4 ELISA and AU-probe). Rabbit
      and patient MRI images were also evaluated and scored. Receiver operating
      characteristic (ROC) curve analysis was applied to various diagnostic methods
      (MRI, ELISA, AU-probe, and arthroscopy), performing comparisons via logistic
      regression. In rabbits, the AU-probe proved nonsuperior to MRI T2 mapping and
      ELISA (fluorescence cutpoint > 864.965 au). In patient groups, logistic
      regression analysis indicated that combined AU-probe/MRI testing outperformed MRI
      alone, thus offsetting low MRI sensitivity and low AU-probe specificity for
      improved detection of mild cartilage injury (sensitivity, 82.5%; specificity,
      80.0%). We have consequently confirmed the efficacy of this AU-probe, using
      ADAMTS-4 activity in synovial fluid to diagnose mild cartilage injury. Combining
      the AU-probe with conventional MRI assessment proved optimal in this setting.

PMID- 30210672
TI  - Development of genistein-PEGylated silica hybrid nanomaterials with enhanced
      antioxidant and antiproliferative properties on HT29 human colon cancer cells.
AB  - The anticancer use of genistein (Gen) has been severely limited due to its low
      water solubility, low bioavailability, and instability under experimental
      conditions. To overcome these limitations, we propose a formulation of a hybrid
      nanomaterial (HNM) based upon the incorporation of Gen into PEGylated silica
      nanoparticles (PEG-SiNPs) (Gen-PEG-SiHNM), where their physicochemical and
      biological effects on HT29 cells were evaluated. Genistein-loaded PEGylated
      silica hybrid nanomaterials were obtained by a simple end effective aqueous
      dispersion method. Physicochemical properties were determined by its mean
      particle size, surface charge, amount of cargo, spectroscopic properties, release
      profiles and aqueous solubility. In vitro biological performance was carried out
      by evaluating its antioxidant capacity and elucidating its antiproliferative
      mechanistic. Results showed that small (ca. 33 nm) and spherical particles were
      obtained with positive surface charge (+9.54 mV). Infrared analyses determined
      that encapsulation of genistein was successfully achieved with an efficiency of
      51%; it was observed that encapsulation process enhanced the aqueous
      dispersibility of genistein and cumulative release of genistein was pH-dependent.
      More important, after encapsulation data showed that Gen potentiated its
      antioxidant and antiproliferative effects on HT29 human colon cancer cells by the
      modulation of endogenous antioxidant enzymes and H2O2 production, which
      simultaneously activated two different processes of cell death (apoptosis and
      autophagy), unlike free genistein that only activated one (apoptosis) in a lower
      proportion. Overall, our data support that Gen-PEG-SiHNM could be potentially
      used as alternative treatment for colorectal cancer in a near future.

PMID- 30210673
TI  - The accurate surgical margin before surgery for malignant musculoskeletal tumors:
      a retrospective study.
AB  - There is no accurate volume measurement method for evaluating the response to
      chemotherapy in malignant musculoskelal tumors, and there is no specific
      preoperative evaluation method to evaluate surgical margins. Twenty-five cases of
      malignant musculoskeletal tumors treated from Mar 2012 to Mar 2014 were analyzed.
      Through the use of a connective slice-scan and augmented virtual reality
      technique, accurate measurement of the tumor volume and determination of surgical
      margins according to the standard proposed by Kawaguchi were easily reached.
      Specimens were sent for a pathological examination to determine the tumor type.
      The preoperative surgical margin was compared with the postoperative surgical
      margin. Curative resection or wide resection facilitated by the preoperative
      imaging data occurred in 92% of patients; only one case resulted in intralesional
      resection for malignant tumor progression, and one case resulted in marginal
      resection for femoral nerve invasion. There was no significant difference between
      the predicted margin before the operation and final margin after the operation
      (P>0.05). Our results demonstrate that application of continuous imaging data
      with enough sectional anatomy detail can provide a scientific basis for measuring
      the size of a tumor and identifying the tumor's surgical margins in multiple
      dimensions using an augmented virtual reality technique.

PMID- 30210671
TI  - Entresto therapy effectively protects heart and lung against transverse aortic
      constriction induced cardiopulmonary syndrome injury in rat.
AB  - This study tested the hypothesis that entresto therapy effectively protected
      heart and lung against cardiopulmonary syndrome (CPS) caused by transverse aortic
      constriction (TAC) in rat. Adult-Male SD rats (n = 36) were equally categorized
      into group 1 [sham-operated control (SC)], group 2 [SC + enalapril (7 mg/kg/day)
      since day-28 after TAC induction], group 3 [SC + entresto (30 mg/kg/day) since
      day-14 after TAC induction], group 4 (TAC only), group 5 (TAC + enalapril) and
      group 6 (TAC + entresto) and euthanized at day 60 after TAC induction. By day 60,
      the left-ventricular (LV) ejection fraction was significantly lower in group 4
      than in other groups and significantly lower in groups 5 and 6 than in groups 1
      to 3, whereas the ratios of heart and lung weights to tibial-length as well as
      the right-ventricular-systolic blood pressure exhibited an opposite pattern among
      the groups (all P<0.001). The sarcomere-length (SL), LV fibrotic area,
      cardiomyocyte size, and lung injury score were highest in group 4, lowest in
      groups 1 to 3 and significantly lower in group 6 than in group 5 (all P<0.0001).
      The protein expressions of fibrotic (Smad3/TGF-beta), apoptotic (mitochondrial
      Bax/cleaved-caspase3/PARP) and DNA-damaged (gamma-H2AX) markers in lung and LV
      myocardium as well as oxidative (NOX-1/NOX2/oxidized protein) in LV myocardium
      exhibited an identical pattern of SL (all P<0.0001). The protein expressions of
      pressure/volume overload (BNP/MHC-beta) mitochondrial-damaged (cytosolic
      cytochrome-C) of LV myocardium exhibited an identical pattern of SL (all
      P<0.001). In conclusion, Entresto is non-inferior to enalapril for protecting the
      heart-lung against CPS.

PMID- 30210674
TI  - Direct factor Xa inhibition attenuates acute lung injury progression via
      modulation of the PAR-2/NF-kappaB signaling pathway.
AB  - The role of coagulation in acute lung injury (ALI) remains unclear. As factor Xa
      dependent protease-activated receptor 2 (PAR-2) is reported to be an important
      target in blood coagulation and other processes, an inhibitor of factor Xa,
      rivaroxaban, was tested in vivo in C57BL/6 mice with ALI induced by intratracheal
      injections of lipopolysaccharide (LPS) and in vitro in LPS-stimulated human
      umbilical vein endothelial cells. Plasma concentrations and coagulation indices
      were measured in mice fed normal chow or chow containing rivaroxaban (0.2 or 0.4
      mg/g) for 10 days. The rivaroxaban-treated mice had significantly reduced
      neutrophil sequestration with preservation of the lung tissue architecture
      compared with that in the untreated controls. The levels of tumor necrosis factor
      alpha, interleukin 1 beta, and interleukin 6, as well as total protein and Evans
      blue concentrations, were all significantly reduced in bronchoalveolar lavage
      fluid from mice treated with rivaroxaban. Rivaroxaban treatment also ameliorated
      the LPS-induced PAR-2 increase and nuclear factor kappa B (NF-kappaB) activation.
      In vitro, cells treated with rivaroxaban had higher cell viability with an
      attenuation of LPS-induced increases in membrane permeability and proinflammatory
      cytokine levels, as well as reduced apoptosis. Furthermore, rivaroxaban inhibited
      the phosphorylation of TAK1 and p65. These data show that rivaroxaban attenuates
      ALI and inflammation by inhibiting the PAR-2/NF-kappaB signaling pathway.

PMID- 30210675
TI  - Serum NOX2 as a new biomarker candidate for HBV-related disorders.
AB  - Growing evidence supports the notion that serum NAPDH oxidase 2 (NOX2) is an
      important regulator that contributes to the initiation and progression of various
      types of diseases. However, so far, it remains elusive about the relationship
      between levels of serum NOX2 and HBV-related diseases. The overall purpose of the
      study is to get a better insight into whether or not serum NOX2 is involved in
      HBV-related disorders. Serum levels of NOX2, from 105 patients with chronic
      hepatitis B, 58 patients with HBV-related cirrhosis, 48 patients with HBV-related
      hepatocellular carcinoma and 104 healthy individuals, were measured with sandwich
      ELISA kits that we developed. In this study, we found that NOX2 values were
      significantly higher in patients compared to healthy control (P < 0.01) and that
      the levels of serum NOX2 were significantly correlated with the serum levels of
      superoxide dismutase (SOD), interleukin-6 (IL-6), interferon-stimulated gene 15
      (ISG15), alkaline phosphatase (ALP) and gamma glutamyl transpeptidase (GGT) in
      chronic hepatitis B, cirrhosis and hepatocellular carcinoma patients.
      Interestingly, we found that a significant positive correlation between NOX2 and
      HBV viral load only in patients with chronic hepatitis B and cirrhosis.
      Therefore, Serum NOX2 levels maybe an important indicator of the pathogenesis of
      progression of HBV-related disorders.

PMID- 30210676
TI  - The neural regeneration effect of chitin biological absorbable tubes bridging
      sciatic nerve defects with sural nerve grafts.
AB  - OBJECTIVE: To investigate the feasibility and efficacy of sural nerve grafts for
      repairing sciatic nerve defects using a chitin biological absorbable tube bridge.
      METHODS: A sciatic nerve defect model in the rat was produced, and the sural
      nerve, cut from the ipsilateral leg, was used as a graft to repair the defect
      using chitin biological absorbable tube bridges. Then the number and morphology
      of regenerating myelinated fibers, nerve function index, nerve conduction
      velocity, and motor end plate and triceps surae muscle morphology were evaluated.
      RESULTS: The number and morphology of regenerated fibers, nerve function index,
      nerve conduction velocity, and motor end plate and triceps surae muscle
      morphology were improved in rats in which the nerve defect was bridged with
      chitin biological absorbable tubes compared with rats in which the defect was
      repaired without tubes. CONCLUSIONS: The findings suggest that using a sural
      nerve graft to repair sciatic nerve defects with chitin biological absorbable
      tubes bridge promotes structural and functional recovery, and improves end plate
      and muscle fiber morphology as well.

PMID- 30210678
TI  - Angiotensin II receptor blocker reverses heart failure by attenuating local
      oxidative stress and preserving resident stem cells in rats with myocardial
      infarction.
AB  - The present study aimed to test whether angiotensin receptor blockers (ARBs) are
      cardioprotective after myocardial infarction (MI) by preventing augmented local
      renin-angiotensin-system (RAS)-induced oxidative stress injury and senescence,
      preserving resident stem cells, and restoring the insulin-like growth factor (IGF
      1)/IGF-1 receptor (IGF-R) pathway. Sprague-Dawley rats with ligated or unligated
      coronary arteries were treated with losartan (20 mg/kg/d) or vehicle for 3 or 9
      weeks. Heart function and molecular and histological changes were assessed. It
      was found MI induced left ventricular dysfunction and remodeling, increased
      levels of the oxidative stress marker 8-hydroxy-2'-deoxyguanosine and cell
      senescence marker p16ink4a, and downregulated the IGF-1/IGF-1R/Akt pathway after
      both 3 and 9 weeks post-MI. MI induced an increase in stem cells identified by
      immunostaining for c-kit and Wilms' tumor-1 predominantly after 3 weeks. Losartan
      significantly inhibited local cardiac RAS activation and improved left
      ventricular function and remodeling at both timepoints. Losartan also preserved c
      kit- and Wilms' tumor-1-positive cells (particularly at 3 weeks), attenuated 8
      hydroxy-2'-deoxyguanosine- and p16ink4a-positive cardiomyocytes, and restored the
      IGF-1/IGF-1R/Akt pathway at both 3 and 9 weeks. In conclusion, ARBs aided cardiac
      repair post-MI through short-term preservation of stem cells and persistent anti
      oxidative stress and anti-senescence effects, partially by attenuating activation
      of cardiac RAS and restoring the local IGF-1/IGF-1R/Akt pathway.

PMID- 30210677
TI  - Transcriptomic profile analysis of brain microvascular pericytes in spontaneously
      hypertensive rats by RNA-Seq.
AB  - BACKGROUND: Changes in the structure and function of micro-vessels is the
      pathogenic basis of organ damage in cardiovascular and cerebrovascular diseases.
      Microcirculation is primarily affected in hypertension, resulting in increased
      vascular resistance. Pericytes are contractile cells that are embedded in the
      basement membrane of capillaries, and regulate endothelial cell membrane
      maturation, capillary blood flow, cell debris removal, and stability of
      endothelial cells. However, the exact role of brain microvascular pericytes in
      the pathogenesis of hypertension has not been elucidated. METHODS: Brain
      microvascular pericytes were isolated from spontaneously hypertensive rats (SHR)
      and wild type Wistar Kyoto (WKY) rats. The transcriptomes of SHR and WKY
      pericytes were analyzed by RNA-Seq, and the differentially expressed genes (DEGs)
      were screened by Ballgown, and Student's t test was used to be used to compare
      differences between groups. DAVID was used for the GO-enrichment analysis and
      KEGG pathway analysis of the DEGs, and an interaction network between the
      significant signaling pathways and DEGs was constructed. RESULTS: A total of 1356
      DEGs were identified between the WKY and the SHR group pericytes (P value < 0.05,
      Fold change > 1.5), of which 733 were upregulated and 623 downregulated. The
      genes with greatest betweenness centrality values were Itgb1, Vcam-1 and MMP-9.
      Based on KEGG analysis, 34 interacting signaling pathways and 43 interacting
      genes were screened, and MAPK, p53, Wnt, Jak-STAT, TGF-beta, VEGF and PPAR
      signaling pathways were the key nodes. CONCLUSIONS: Several DEGs and signaling
      pathways were identified in the brain microvascular pericytes of SHR rats
      compared to the WKY rats. Our findings will lay the foundation to study the role
      of brain microvascular pericytes in the development of spontaneous hypertension.

PMID- 30210679
TI  - Extracellular galectin-3 facilitates colon cancer cell migration and is related
      to the epidermal growth factor receptor.
AB  - We previously found that galectin-3 enhanced DLD-1 cell migration through the K
      Ras-Raf-Erk1/2 pathway, but the effect of extracellular galectin-3 on cancer cell
      migration and its interaction with the epidermal growth factor receptor (EGFR)
      remained unknown. We aimed to determine the effect of extracellular galectin-3 on
      colon cancer cell migration and its correlation with the EGFR expression. Western
      blotting was performed to analyze galectin-3 secretion, shRNA was used to stably
      knock down galectin-3 expression and a migration assay was performed to evaluate
      colon cancer cell migration. Tissues from eighty patients with four different
      stages of colon cancer were obtained and compared to normal colon tissue. The
      galectin-3 knockdown colon cancer cells exhibited decreased migration, which was
      restored by recombinant galectin-3. An EGFR blocking antibody decreased colon
      cancer cell migration. The addition of recombinant galectin-3 increased
      phosphorylated EGFR expression within minutes and enhanced the internalization of
      the EGFR from the cell membrane to the cytoplasm, particularly upon EGF
      stimulation. Extracellular galectin-3 increased colon cancer cell migration,
      which correlated with the EGFR. Targeting galectin-3 may have a synergistic
      effect on EGFR-targeted therapy.

PMID- 30210680
TI  - Measurement of lumbar isthmus parameters for novel starting points for cortical
      bone trajectory screws using computed radiography.
AB  - The current study aims to measure distance parameters in lumbar isthmus to
      develop new references for lumbar pedicle screw insertion. Using computed
      radiography, the distance between the median pedicle tangent and the isthmus
      lateral tangent (D1) and the isometric distance between the isthmus lateral
      tangent and the inferior border of transverse process (D2) were measured on 120
      spine X-ray images. A derived distance D3 (equal to D2 minus 1 mm) was
      calculated. These parameters were used to define the starting points for pedicle
      screws. Cortical bone trajectory (CBT) fixations were carried out on six wet
      (including 3 male and 3 female) and 4 dry lumbar specimens using the new system,
      and were evaluated for accuracy and safety of screw insertion. Measurements
      showed that D1 (mm) was 2.1+/-0.13 (L1), 2.3+/-0.13 (L2), 3.6+/-0.33 (L3), 4.4+/
      0.36 (L4), 5.7+/-0.36 (L1); D2 was 5+/-0.83 (L1), 6.19+/-0.84 (L2), 5.38+/-0.86
      (L3), 3.66+/-0.42 (L4) and 2.30+/-0.37 (L5). A total of 100 CBTs were evaluated.
      Among them, 7 out of the 60 screws in the 6 wet specimens penetrated into the
      lateral pedicle bone, the successful rate was 88.7%; 2 out of the 40 screws in
      the 4 dry specimens penetrated through the lateral or median pedicle bone, the
      successful rate was of 95%. With our new system, CBT screws can be placed based
      on these parameters, which can be obtained less invasively, and irrespective of
      articular degeneration in lumbar facet and morphological variation in the
      transverse process. Our data show that the technique is safer, less invasive, and
      easier to operate. It would help reduce bleeding, intraoperative X-ray exposure
      and surgical time.

PMID- 30210681
TI  - Anticancer effects of plant derived Anacardic acid on human breast cancer MDA-MB
      231 cells.
AB  - Triple negative breast cancer (TNBC) accounts for about 10-15% of all breast
      cancers. It is a heterogeneous disease, characterized by early relapse,
      aggressive behavior, and poor prognosis, when compared to other breast cancer
      subtypes. Interestingly, most of the heat shock protein 90 (Hsp90) client
      proteins are oncoproteins, and some are closely related to the key factors that
      promote the progression of TNBC. Anacardic acid (AA), which is commonly seen in
      natural plants of Anacardiaceae, exhibits potent Hsp90 ATPase inhibition
      activity. In this study, the anticancer effects of AA on TNBC MDA-MB-231 cells
      were investigated. The results of our study showed that AA inhibited cell
      proliferation, induced G0/G1-phase cell cycle arrest, suppressed cell invasion
      and migration, and induced apoptosis in the MDA-MB-231 cells. Regulation of the
      key Hsp90-dependent tumor-related molecules or endoplasmic reticulum stress (ERS)
      related molecules, such as GRP78, Hsp70, CDK-4, MMP-9, Bcl-2, and Mcl-1 by AA may
      be related to these effects. Taken together, our results suggest that AA shows
      potential as a possible new drug for therapy of TNBC.

PMID- 30210682
TI  - Anesthesia and surgery induce delirium-like behavior in susceptible mice: the
      role of oxidative stress.
AB  - Anesthesia and surgery (A + S) are risk factors for patients to develop
      postoperative delirium (POD). However, the pathogenesis of POD remains largely to
      be determined. We employed battery of behavioral tests including open-filed test
      (OFT), elevated plus maze test (EPMT) and buried food test (BFT) to investigate
      the role of oxidative stress in the development of POD and to explore the
      therapeutic target for POD in mice after A + S (simple laparotomy under 1.4%
      isoflurane anesthesia). We initially found that 6 hours after A + S, mice failed
      to alter the behavioral changes in OFT and the adenosine triphosphate (ATP) level
      in hippocampus. After hierarchical cluster analysis, however, there was a
      significant change in the behavior tests between POD unsusceptible (non-POD) and
      susceptible (POD-like) mice. Interestingly, cyclosporine A, an inhibitor of
      mitochondrial permeability transition pore (mPTP) opening, exerted
      pharmacologically beneficial effects on symptoms, decreased reactive oxygen
      species (ROS) and ATP, and increased superoxide dismutase (SOD), glutathione
      peroxidase (GSH-Px) and catalase (CAT) levels in the hippocampus of POD-like
      mice. These findings suggest that abnormally activated oxidative stress might be
      involved in the underlying mechanisms of POD. Novel therapeutic agents targeting
      inhibition of oxidative stress would provide an available strategy for POD
      treatment.

PMID- 30210683
TI  - Islet transplantation attenuates cardiac fibrosis in diabetic rats through
      inhibition of TGF-beta1/Smad3 pathway.
AB  - Although islet transplantation has been identified as a promising endocrine
      replacement treatment for patient with diabetes mellitus (DM), it still remains
      unclear whether islet transplantation can inhibit the diabetic-induced myocardial
      injury and subsequent adverse ventricular remodeling. Here, we sought to explore
      the molecular mechanism underlying the cardioprotective effect of islet
      transplantation. We established the diabetic rat model by intraperitoneal
      injection of STZ, which was followed by either islet transplantation or
      conventional insulin treatment. Compared with insulin treatment, islet
      transplantation further reduced the elevated blood glucose which was nearly
      restored to normoglycaemia. In addition, islet transplantation attenuated the
      increased levels of cTn-I and CK-MB, cleaved-caspase-3 in response to DM, and
      ameliorated diabetic-induced cardiac hypertrophy and interstitial fibrosis, along
      with improved extracellular matrix (ECM) deposition. Moreover, diabetic rats that
      underwent islet transplantation had lower expression of TGF-beta1 and lower
      phosphorylation levels of Smad3. Therefore, islet transplantation exerted
      protective effect against diabetic-induced myocardial injury and fibrotic
      remodeling through deactivation of TGF-beta1/Smad3 signaling pathway.

PMID- 30210684
TI  - MicroRNA-144-3p inhibits cell proliferation and induces cell apoptosis in
      prostate cancer by targeting CEP55.
AB  - Previous research reported that miR-144-3p functions as tumor suppressor in
      several tumors, including glioblastoma and hepatocelluar carcinoma, but the role
      of miR-144-3p in prostate cancer (PCa) remains unclear. In this study, we aimed
      to analyze the role of miR-144-3p in PCa. By RT-qPCR, we found that expression of
      miR-144-3p was markedly down-regulated in PCa tissues and cell lines compared
      with that in paired adjacent normal tissues and normal cell lines. Moreover, miR
      144-3p overexpression in PC-3 and DU145 cells by transfection with miR-144-3p
      mimics significantly inhibited cell proliferation and in vitro by MTT, colony
      formation assays and suppressed tumor growth in vivo by nude mice model. Flow
      cytometry analysis further demonstrated that forced expression of miR-144-3p
      induced cell cycle G1/S phase arrest and apoptosis. Moreover, centrosomal protein
      of 55 (CEP55) was confirmed as a direct target of miR-144-3p by bioinformatics
      analysis and luciferase reporter assays. Overexpression of miR-144-3p decreased
      the CEP5 mRNA and protein levels in PC-3 and DU145 cells. Using Oncomine database
      analysis, we further found the expression of CEP55 was significantly upregulated
      in PCa tissues. In addition, knockdown of CEP55 elicited similar effects with miR
      144-3p overexpression in PCa cells. Taken together, our results demonstrate that
      miR-144-3p functions as a tumor suppressor in PCa by downregulating CEP55,
      supporting the targeting miR-144-3p might be a potentially effective therapeutic
      approach for PCa.

PMID- 30210685
TI  - Collagen type V a2 (COL5A2) is decreased in steroid-induced necrosis of the
      femoral head.
AB  - Collagen is essential for bone adhesion and formation. In the present study,
      proteomic analysis suggested that collagen type V a2 (COL5A2) was significantly
      decreased in the necrotic area of patients with steroid-induced necrosis of the
      femoral head (ONFH). In vitro, the effects of methylprednisolone (MP) on the
      proliferation and differentiation of human bone marrow-derived mesenchymal stem
      cells (hBMSCs) were investigated. The expression of the osteogenic-related
      proteins, Runx2, alkaline phosphatase (ALP), osteocalcin (OC) and COL5A2 was
      significantly downregulated post-MP treatment. In vivo analyses revealed that
      post-MP treatment, rats showed typical signs of ONFH by micro-CT scanning and
      hematoxylin and eosin (H&E) staining. Immunohistochemical staining demonstrated
      that the expression of COL5A2 and vascular endothelial growth factor (VEGF) was
      significantly decreased post-MP treatment. In conclusion, the expression COL5A2
      was lower in patients with steroid-induced ONFH, hence COL5A2 may be a promising
      therapeutic target for steroid induced ONFH treatment.

PMID- 30210686
TI  - E7 peptide-functionalized Ti6Al4V alloy for BMSC enrichment in bone tissue
      engineering.
AB  - Ti6Al4V alloy is widely used for hip joint prostheses, however owing to its lack
      of biomimetic surface properties, it often suffers from poor osseointegration. It
      is well known that bone mesenchymal stem cells (BMSCs) play an important role in
      the osseointegration of the host bone and joint prostheses. One promising
      approach to improving the osseointegration of joint prostheses is to enrich the
      number of BMSCs at the periprosthetic site. Previous studies have reported that
      BMSC specific affinity peptide E7, can specifically enrich BMSCs. However, to
      date, few studies have reported the use of E7 in bone tissue engineering. In this
      study, we conjugated E7 peptide to Ti6Al4V alloy to fabricate a scaffold (BTS) to
      improve the biocompatibility of the alloy. E7 peptide efficiently improved the
      adhesion of BMSCs to Ti6Al4V alloy. In addition, the BTS scaffold was more
      conducive to osteogenesis than the RGD-functionalized and non-functionalized
      control scaffolds. The functional BTS scaffold could pave the way for designing
      functional joint prostheses, which promote osseointegration between the host bone
      and implant.

PMID- 30210687
TI  - Huangqi (astragalus) decoction ameliorates diabetic nephropathy via IRS1-PI3K
      GLUT signaling pathway.
AB  - Huangqi decoction (HD) is a prescription for the treatment of diabetes in
      traditional Chinese medicine. The study was aimed to investigate the effect of HD
      on diabetic nephropathy. Male diabetic db/db mice which develop diabetic
      nephropathy spontanously and non-diabetic db/m control mice were used in the
      current study, and received the treatment of HD for 14 consecutive weeks. HD
      treatment dose-dependently decreased the body weight, urine volume, water intake
      and food intake, improved glucose tolerance and insulin resistance, and lowered
      blood glucose, serum glycosylated hemoglobin, insulin and insulin resistance
      index in db/db mice. The db/db mice also showed low levels of serum creatinine,
      blood urea nitrogen and urine albumin, and improved renal functions such as
      glomerular filtration rate after HD treatment. Histological examination showed
      that HD treatment prevented the deterioration of basement membrane of glomerular
      capillary, mesangial matrix and renal tubular lumen in the db/db mice. Through
      examining the cell signaling pathways which might be involved in the pathology of
      diabetic nephropathy, we found that HD treatment activated phospho-IRY1361,
      phospho-IRS1Y896, phospho-PI3K, and inhibited phospho-IRS1S636/639, phospho
      AKTT308 and phospho-AKTS473. HD treatment abolished the change in the expression
      of glucose transporters in the diabetic kidney with an increase in GLUT4 but
      decrease in GLUT1 expression in the kidney in a dose-dependent manner. Our study
      suggests that HD prevents the development of diabetes and improves renal function
      in the db/db mice and HD regulation of the IRS1-PI3K-GLUT signaling pathway
      significantly improves diabetic nephropathy.

PMID- 30210688
TI  - Polysaccharide extracted from Portulacae Oleracea L. exerts protective effects
      against dextran sulfate sodium-induced colitis through inhibition of NF-kappaB.
AB  - Portulacae Oleracea L. (POL) is a traditional Chinese medicine and also an edible
      vegetable used to treat diarrhea in china for thousands years. Though the
      therapeutic effect has been proved in clinical trials, the concrete effective
      component and mechanisms remained elusive. Polysaccharide from POL has been
      extracted previously and the experiment suggested that POLP could diminish the
      weight loss and improve the health conditions of mice with DSS induced colitis.
      Hematoxylin & eosin staining revealed that POLP could improve the
      histopathological structure of the colon tissue. For the notably variation curve
      of TNF-alpha in control, colitis and treatment group, NF-kappaB was enrolled to
      investigate the molecular mechanisms of the protective effect of POLP. The
      protein expression level of NF-kappaBp65 in cytoplasm increased after POLP
      treatment of the induced colitis. However, the protein level of NF-kappaBp65 in
      the nucleus decreased after administration of POLP. The expression levels of
      IkappaBalpha and NF-kappaB related proteins Bcl-2 and survivin were also detected
      and the results suggested that POLP could inhibit the degradation of IkappaBalpha
      and decrease the protein levels of Bcl-2 and Survivin in colitis. It was
      concluded that POLP could improve the health condition of mice with DSS induced
      colitis and the mechanisms were closely related with NF-kappaB via inhibiting the
      degradation of IkappaBalpha.

PMID- 30210689
TI  - Transcription factor Tbx18 induces the differentiation of c-kit+ canine
      mesenchymal stem cells (cMSCs) into SAN-like pacemaker cells in a co-culture
      model in vitro.
AB  - Bone mesenchymal stem cells (MSCs), as well as cardiomyocytes, are derived from
      early mesoderm, becoming committed to their fate under the influence of different
      differentiation factors. We examined whether the overexpression of Tbx18 can
      induce the differentiation of c-kit+ cMSCs into a phenotype similar to that of
      native pacemaker cells and whether these transfected cells can couple to adjacent
      atrial cells with functional consequences. The c-kit+ cMSCs were first sorted,
      then transfected with different lentiviral vectors. Tbx18-c-kit+ cMSCs
      represented the experimental group, while EYFP-c-kit+ cMSCs and canine sinoatrial
      node (SAN) cells were used as controls. Within days of transfection, the
      hyperpolarization-activated cyclic nucleotide-gated (HCN) channel HCN4 protein
      and gap junction protein Connexin 45 (Cx45) expression in Tbx18-c-kit+ cMSCs were
      12-fold and 5.6-fold higher, respectively, than that in EYFP-c-kit+ cMSCs. After
      co-culture with canine atrial cells in vitro for three days, the funny currents
      (If) were recorded in the Tbx18-c-kit+ cMSCs, but not in EYFP-c-kit+ cMSCs. The
      trend of these If currents was highly similar to that of SAN cells, although the
      current density was smaller. The Tbx18-EYFP-c-kit+ cMSCs showed responsiveness to
      beta-adrenergic stimulation, and the intracellular cyclic adenosine monophosphate
      (cAMP) level was higher than that in EYFP-c-kit+ cMSCs. The Tbx18-EYFP-c-kit+
      cMSCs delivered fluorescent dye to neighboring atrial cells via gap junctions,
      thus these cell pairs could communicate as a pacemaker unit. We propose that the
      overexpression of Tbx18 in c-kit+ cMSCs induces their differentiation to SAN-like
      pacemaker cells.

PMID- 30210690
TI  - Kindlin-2-mediated upregulation of ZEB2 facilitates migration and invasion of
      oral squamous cell carcinoma in a miR-200b-dependent manner.
AB  - The miR-200 family suppresses epithelial-mesenchymal transition by inhibiting
      ZEB1 and ZEB2 mRNA translation in several types of cancers. Kindlin-2 is a target
      gene of miR-200b and its expression level correlates positively to ZEB2 in oral
      squamous cell carcinoma (OSCC). Whether Kindlin-2 and ZEB2 share a competitive
      endogenous RNAs regulatory network in OSCC remains unclear. Here, we studied the
      expression levels of miR-200b, Kindlin-2, and ZEB2 and found direct interaction
      between miR-200b, ZEB2, and Kindlin-2 mRNA in OSCC. A series of experiments was
      performed to elucidate the role of miR-200b and Kindlin-2 in OSCC cells. To
      further investigate whether Kindlin-2 regulates ZEB2 as a "ceRNA", we utilized
      pools of siRNAs to deplete Kindlin-2 or ZEB2 in Tca-8113 cells. Significantly
      elevated expression levels of Kindlin-2 and ZEB2, down-regulated mRNA levels of
      miR-200b, and a positive correlation between Kindlin-2 and ZEB2 were found in
      OSCC cells. Additional results suggest that miR-200b directly targets ZEB2 and
      that Kindlin-2 3'UTR miR-200b repressed both the migration and invasive
      functionality of Tca-8113. Kindlin-2 and ZEB2 are involved in accelerated
      migration and invasion of Tca-113 cells in vitro and Kindlin-2 controlled ZEB2
      expression. However, Kindlin-2-mediated ZEB2 regulation did not depend on miRNAs.
      These results indicate that Kindlin-2 does not act as ZEB2 ceRNA and modify the
      migration of Tca-8113 cells. Our results improve our understanding of the
      underlying molecular and cellular mechanisms of oral cancer metastasis.

PMID- 30210691
TI  - LOX inhibitor HOEC interfered arachidonic acid metabolic flux in collagen-induced
      arthritis rats.
AB  - Arachidonic acid (AA) metabolic network generates a variety of products that
      mediate or modulate inflammatory reactions. (+)-2-(1-hydroxyl-4-oxocyclohexyl)
      ethyl caffeate (HOEC), isolated from Incarvillea mairei var. granditlora
      (Wehrhahn) Grierson, was found as an inhibitor of 5-LOX and 15-LOX in vitro. When
      evaluated in collagen-induced arthritis (CIA) rats, however, lowdose of HOEC (1
      mg/kg) showed better efficacy than that of high dose (10 mg/kg). To study how
      HOEC interfered the AA metabolic pathway, in this study, we dynamically observed
      the changes of plasma AA metabolites (LTB4, LTC4, 15-HETE, PGE2, TXB2 and PGD2)
      in the CIA rats treated with different doses of HOEC by using enzyme-linked
      immunosorbent assay (ELISA). The results showed that eicosanoids were elevated
      synchronously at three time points in different treated rats. The incidence of
      arthritis had a higher correlation with LOX pathway while the COX pathway might
      be more important in the severity of arthritis. HOEC in all doses could inhibit
      LOX pathway in the beginning of arthritis while highdose of HOEC could induce the
      increase of COX metabolites in the later stage of disease. These dynamic changes
      of eicosanoids, depending on the regulation of metabolic flux, can be interfered
      by HOEC and thus affect the output of efficacy.

PMID- 30210692
TI  - Apoptosis of bone marrow mesenchymal stromal/stem cells via the MAPK and
      endoplasmic reticulum stress signaling pathways.
AB  - Therapy for myocardial regeneration using bone marrow stromal cells (BM-MSCs) has
      been applied to improve the cardiac function of subjects with acute myocardial
      infarction. However, the study of this therapy has encountered a bottleneck
      because BM-MSCs are prone to apoptosis in ischemic and anoxic environments. The
      goal of this study was to investigate the expression of mitogen activated protein
      kinase (MAPK) (p-38, JNK and ERK) and endoplasmic reticulum stress protein
      (caspase-12 and CHOP) during BM-MSC apoptosis. In a BM-MSC model of hypoxia and
      serum deprivation (H/SD), we observed the morphology and apoptotic rate of BM
      MSCs for 24 h and found that the nuclear shrinkage and apoptosis rate increased
      gradually and reached a maximum apoptosis rate at the 6 h time point. Then, with
      the prolongation of the hypoxia time, the number of nuclear shrinkage cells and
      the apoptosis rate gradually decreased. The expression levels of p-38, JNK, ERK,
      procaspase-12, caspase-12 and CHOP increased at each H/SD time point. In
      addition, compared with the H/SD 6 h group, the nuclear shrinkage and apoptosis
      rate were decreased in the SB202190 and SP600125 groups but increased in the
      PD98059 group. Further, the expression of caspase-12 in the SB202190 group
      decreased, while the expression of procaspase-12 increased, compared with the
      H/SD 6 h group. Overall, our findings suggested that p-38, JNK, CHOP and caspase
      12 play important roles in promoting the apoptosis of BM-MSCs, while ERK is
      contrary to other signals. Moreover, the apoptosis of BM-MSCs was induced by H/SD
      via the p-38-caspase-12 signaling pathway.

PMID- 30210693
TI  - Effects of chidamide and its combination with decitabine on proliferation and
      apoptosis of leukemia cell lines.
AB  - Chidamide, a novel histone deacetylase inhibitor (HDACI), shows anticancer
      ability against leukemia and solid tumors. Decitabine (5-Aza-2'-deoxycytidine,
      DAC), an anti-leukemic drug, is effective in treating acute myeloid leukemia
      (AML) and myelodysplastic syndrome (MDS). In our study, we investigated the anti
      leukemic ability of chidamide, as well as its combination with decitabine in
      leukemia cells (HL60 and NB4). The results showed that the inhibitive effect of
      chidamide was dose- and time-dependent at concentration of 0.25-8 MUM. The
      proliferation of HL60 and NB4 cells were significantly inhibited by chidamide or
      its combination with decitabine. The combination had a remarkable synergistic
      anti-leukemic effect. Chidamide increased the levels of acetylated histone H3 in
      both HL60 and NB4 cells by effectively inhibiting histone deacetylases (HDAC)
      enzymatic activities. The cells were blocked in G0/G1 phase by chidamide, but
      when chidamide was combined with decitabine, the cell cycle was mainly blocked in
      G2/M phase, accompanied by the induction of p21 expression. In both cases
      (chidamide or chidamide combined with decitabine), apoptosis of tumor cells was
      induced through up-regulation of Bax and Caspase-3, and down-regulation of Bcl-2,
      showing a synergistic cytotoxicity. In conclusion, our results suggested that
      chidamide in combination with decitabine might be an effective therapy for AML.

PMID- 30210694
TI  - Species-specific function of microRNA-7702 in human colorectal cancer cells via
      targeting TADA1.
AB  - Colorectal cancer (CRC) is highly invasive, and an increasing number of studies
      report that microRNAs (miRNAs) are involved in CRC cell invasion and metastasis.
      However, these studies focus on miRNAs with clear functional targets, often
      overlooking obscure miRNAs. Using TCGA data analysis, we compared differentially
      expressed miRNAs in colon and rectal adenocarcinoma (stages N0 and N1/N2) to
      identify miRNAs involved in invasion and metastasis; one identified candidate
      miRNA was miR-7702. Bioinformatics analysis identified TADA1 as a possible target
      gene of miR-7702. The relationship between TADA1 and miR-7702 was analyzed using
      the Oncomine database, CRC tissues at different stages, and CRC cell lines with
      different metastatic properties. We used a dual luciferase-reporter assay to
      verify the interaction between miR-7702 and TADA1. We altered miR-7702 and TADA1
      expression levels using transfection, and measured cell migration and invasion
      abilities. The results revealed a negative correlation between miR-7702 and TADA1
      in CRC. miR-7702 was significantly downregulated in human CRC cell lines with
      high invasion capacity. Its overexpression suppressed human CRC cell migration
      and invasion by directly inhibiting TADA1. This regulatory effect of miR-7702 on
      TADA1 was observed in human CRC cells but not in mouse cells. These findings
      indicate that miR-7702 acts as a tumor suppressor in CRC by inhibiting cell
      migration and invasion, possibly through direct TADA1 inhibition. Our results
      demonstrate for the first time that miR-7702 and TADA1 are biologically
      functional in human CRC cells and reveal that the presence and function of miR
      7702 may be species-specific.

PMID- 30210695
TI  - Role of miRNA-21/PTEN on the high glucose-induced EMT in human mesothelial
      peritoneal cells.
AB  - OBJECTIVE: To explore the effects of miRNA-21/phosphatase and tensin homolog
      (PTEN) on the high glucose-stimulated epithelial-to-mesenchymal transition (EMT)
      in human peritoneal mesothelial cells (HPMCs). METHODS: HPMCs were cultured under
      control conditions, or with high glucose (HG), HG with miRNA-21 mimic or a miRNA
      21 inhibitor. Expression of miRNA-21, alpha-smooth muscle actin, >fibronectin, E
      cadherin and PTEN were measured by real time PCR, Western blotting and
      immunofluorescence staining. RESULTS: Compared with the control, HG induced the
      EMT, as shown by upregulation of alpha-smooth muscle actin and >fibronectin, and
      downregulation of E-cadherin. We also found that HG upregulated miRNA-21
      expression and downregulated PTEN expression; the miRNA-21 inhibitor attenuated
      the HG-induced EMT in HPMCs by targeting PTEN; the miRNA-21 mimic increased the
      HG-induced EMT in HPMCs by targeting PTEN. CONCLUSIONS: This study demonstrated
      that miRNA-21 played a vital role in the HG-induced EMT by targeting PTEN in
      HPMCs.

PMID- 30210696
TI  - MiR-185 inhibits tumor growth and enhances chemo-resistance via targeting SRY
      related high mobility group box transcription factor 13 in non-small-cell
      carcinoma.
AB  - MicroRNA-185 (miR-185) is down-regulated in various tumor types. However, the
      cytological mechanism for inhibiting and restraining tumor growth of non-small
      cell carcinoma (NSCLC) remains to be elucidated. In this study, it was revealed
      that miR-185 is significantly down-regulated in both NSCLC tumor tissues and cell
      lines, and over-expression of miR-185 inhibited cell growth, migration and
      invasion. To investigate the cellular machinery involved in miR-185's regulation
      of tumor growth, it was found that miR-185 directly targets SRY-Box 13 (SOX13).
      In addition, miR-185 regulated cell proliferation, migration, invasion and
      increased chemo-sensitivity in H1975 cells by inhibiting SOX13. MiR-185 also
      inhibited tumor growth and suppressed SOX13 in nude mouse xenograft tumors. To
      investigate the clinical relevance of these consequences, 24 pairs of NSCLC
      tissues and adjacent normal tissues were collected to determine expression of miR
      185 and SOX13. It was demonstrated that miR-185 levels are significantly and
      inversely correlated with SOX13 levels in these NSCLC tissues, suggesting that
      these findings have implications for translational application with respect to
      NSCLC diagnostics and therapy.

PMID- 30210697
TI  - Lithium chloride inhibits cell survival, overcomes drug resistance, and triggers
      apoptosis in multiple myeloma via activation of the Wnt/beta-catenin pathway.
AB  - Multiple myeloma (MM) is an extremely malignant plasma cell disease, which is
      still incurable due to its drug resistance. Lithium chloride (LiCl) functions in
      many pathological processes, including bipolar disorder, acute brain injuries,
      and chronic neurodegenerative diseases, but its antagonistic role in MM
      progression has not been reported thus far. In this study, we found that LiCl
      inhibited MM cell proliferation and induced MM cell cycle G2/M phase arrest in a
      dose-dependent manner. Moreover, LiCl overcomes bortezomib (BTZ)-mediated
      resistance in MM cells and induces apoptosis in BTZ-resistant cells. Our data
      preliminarily indicate that LiCl induces MM cell apoptosis via activating the
      Wnt/beta-catenin signaling pathway. Overall, our results define LiCl as an
      inducer of MM cell apoptosis and unveil a crosstalk between BTZ and LiCl in
      facilitating cell apoptosis.

PMID- 30210698
TI  - Identification and differentiation therapy strategy of pterygium in vitro.
AB  - Pterygium is an invasive hyperplasia, resulting from the hyper-proliferation of
      epithelial cells in cornea. The aim of our present study is to identify stem
      cells derived from pterygiums and detect differentiation strategy of the
      pterygium stem cells in vitro. Fundamental properties of the cultured pterygium
      stem cells were mainly studied using immunofluorescence staining. While clone
      formation and MTT assay were utilized to evaluate the cell viability. Pterygium
      stem cells could be cultivated easily, expanded efficiently, but expressed
      multilineage stem cell markers, which could be differentiated into neuron,
      osteocytes and adipocytes in vitro. Pterygium-derived spheres expressed stem cell
      markers and the epithelial-mesenchymal transition markers after treating with the
      inducing assays. Proliferation and viability of pterygium stem cells could be
      inhibited after inducing differentiation indicating that differentiation strategy
      will be a promising strategy in future therapies of pterygium. Cells derived from
      pterygiums express multilineage stem cell markers and could be induced
      differentiation. Differentiation therapy strategy could inhibit pterygium stem
      cell in vitro.

PMID- 30210699
TI  - Human mesenchymal stem cells attenuate hyperoxia-induced lung injury through
      inhibition of the renin-angiotensin system in newborn rats.
AB  - Hyperoxia induces activation of the renin-angiotensin system (RAS) in newborn rat
      lungs. This study investigated the therapeutic effects of human mesenchymal stem
      cells (MSCs) on lung development and RAS expression in neonatal rats exposed to
      hyperoxia. Sprague-Dawley rat pups were exposed to either room air (RA) or oxygen
      enriched atmosphere (O2) treatment from postnatal days 1 to 14. Human MSCs (1 *
      105 cells) in 0.03 mL of normal saline (NS) were administered intratracheally on
      postnatal day 5, and four study groups were obtained: RA + NS, RA + MSCs, O2 +
      NS, and O2 + MSCs. The lungs were excised for cytokine, expression of RAS
      components, and histological analyses on postnatal day 14. Body and lung weights
      were significantly lower in rats reared in hyperoxia than in those reared in RA.
      The rats reared in hyperoxia and treated with NS exhibited significantly higher
      tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 levels, mean linear
      intercept (MLI), and expression of angiotensin II, angiotensin II type 1
      receptor, and angiotensin-converting enzyme than those reared in RA and treated
      with NS or MSCs did. Administering MSC to hyperoxia-exposed rats reduced TNF
      alpha and IL-6 levels, improved MLI, and decreased expression of angiotensin II,
      angiotensin II type 1 receptor, and angiotensin-converting enzyme to normoxic
      levels. Thus, human MSCs attenuated hyperoxia-induced lung injury through
      inhibition of the RAS in newborn rats.

PMID- 30210700
TI  - Survival associated alternative splicing events in diffuse large B-cell lymphoma.
AB  - Growing evidence has revealed that the initiation of various malignancies is
      closely associated with alternative splicing (AS) events in certain key
      oncogenes. However, in diffuse large B-cell lymphoma (DLBCL), there is still a
      great deal to learn about AS variants. In this study, 33,724 AS variant profiles
      were obtained from 16,278 genes in 48 DLBCL cases. A total of 10 AS variants were
      identified as overall survival (OS)- related events via multivariate Cox
      regression analysis. Notably, alternative donor (AD) sites in AS events in the
      low-risk group showed a significantly better outcome in DLBCL patients than in
      the high-risk group (P=0.0002). The area under the curve (AUC) of the receiver
      operator characteristic curve (ROC) for ADs in DLBCL was 0.746. Furthermore, 66
      related splicing factors were obtained to investigate their potential
      correlations with AS events. Factors SF1, HNRNPC, HNRNPD, and HNRNPH3 were
      significantly involved in different OS-related AS variants. Collectively, we
      constructed valuable prognostic predictors for DLBCL patients and mapped novel
      splicing networks for further investigation of the underlying mechanisms related
      to AS variants in DLBCLs.

PMID- 30210701
TI  - Long non-coding RNA LINC00346, LINC00578, LINC00673, LINC00671, LINC00261, and
      SNHG9 are novel prognostic markers for pancreatic cancer.
AB  - Pancreatic cancer (PC) is a devastating human disease with aggressive course and
      extremely poor prognosis. Long non-coding RNAs (lncRNAs) have been studied to
      serve as a critical role in pancreatic development and progression. However,
      little is known about its expression pattern, biological function in PC. In our
      study, we measured the expression levels of six lncRNAs (LINC00346, LINC00578,
      LINC00673, LINC00671, LINC00261, and SNHG9) in PC tissues and serums. The results
      showed that LINC00346, LINC00578, and LINC00673 were highly expressed, whereas
      LINC00671, LINC00261, and SNHG9 were lowly expressed in PC tissues and serums,
      and their expression levels were correlated with clinical stages. Results from
      receiver operating characteristic (ROC) curve analysis showed that the area under
      the curve (AUC) of six lncRNAs was 0.7073, 0.7837, 0.6093, 0.6057, 0.5712, and
      0.5983, respectively. Survival analysis indicated that patients with high
      expression of LINC00346, LINC00578, or LINC00673 had significantly lower survival
      rate, while patients with high expression of LINC00671, LINC00261, and SNHG9 had
      significantly higher survival rate. In addition, we also found that silence of
      LINC00346, LINC00578 and LINC00673 inhibited PC cell proliferation, and silence
      of LINC00671, LINC00261, and SNHG9 promoted PC cell proliferation. Therefore, we
      suggested that LINC00346, LINC00578, LINC00673, LINC00671, LINC00261, and SNHG9
      may be novel prognostic markers for PC.

PMID- 30210702
TI  - Stretched-exponential model diffusion-weighted imaging as a potential imaging
      marker in preoperative grading and assessment of proliferative activity of
      gliomas.
AB  - PURPOSE: To assess the feasibility of using diffusion-weighted imaging (DWI) with
      the stretched-exponential model (SEM) for glioma grading and determining the
      correlations among parameters and proliferating cell nuclear antigen and Ki-67
      expression. MATERIALS AND METHODS: Mono-exponential model-DWI (MEM-DWI) and SEM
      DWI were performed in 104 patients with pathologically proven gliomas. The
      patients were divided into the training set (n = 72) and test set (n = 32).
      Apparent diffusion coefficient (ADC), solid tumor distributed diffusion
      coefficient (DDC), and whole tumor alpha values were measured. These parameters
      were applied as cut-off values to determine the predictive accuracy.
      Proliferating cell nuclear antigen and Ki-67 expression correlated with all
      parameters. RESULTS: Significant differences between low-grade gliomas (LGG) and
      high-grade gliomas (HGG) were observed for all parameters (P < 0.05), and
      significant differences in the ability of DDC to distinguish between any two
      glioma grades (P < 0.05) were also evident. DDC showed the highest sensitivity
      and specificity for glioma grading and was negatively correlated with Ki-67 and
      proliferating cell nuclear antigen expression. DDC also showed greater predictive
      accuracy than ADC and alpha. CONCLUSION: SEM-DWI offers a better approach for
      glioma grading than MEM-DWI, and DDC may be a better imaging biomarker for
      grading and evaluating the proliferative activity of brain gliomas.

PMID- 30210703
TI  - Cyclin A2 regulates symmetrical mitotic spindle formation and centrosome
      amplification in human colon cancer cells.
AB  - Colon cancer is one of the most fatal cancers in the United States, and is
      characterized by the presence of chromosomal instability (CIN), causes of which
      are largely unclear. Emerging evidence indicates that abnormal spindle geometry
      and supernumerary centrosomes lead to CIN in cells. However, if and how spindle
      geometry defects and centrosomes amplification occur in colon cancer remains
      unknown. Here we show that decrease in the cell cycle regulatory protein, cyclin
      A2, induces spindle geometry defects in colon cancer cells. In mechanistic
      studies, we found that cyclin A2 is located at the centrosomes, and its depletion
      reduces phosphorylation of EG5, which is important for centrosome localization
      and movement of duplicated centrosomes to opposite poles. We also found that
      cyclin A2 silencing leads to centrosome amplification in the cells. Collectively,
      these findings demonstrate previously unrecognized role for cyclin A2 in
      preventing centrosomal defects in colon cancer cells and provide insights into
      mechanisms that may potentially cause CIN in these tumors.

PMID- 30210704
TI  - The expression of PD-1 and LAG-3 in periapical lesions.
AB  - Periapical lesions are the distinct result of chronic root canal infection and
      could generate severe bone resorption surrounding apical regions. Despite the
      local cytokine and cell-mediated immune responses, periapical lesions are also
      characterized by its auto-restrict inflammation. However, the detailed mechanism
      related to its auto-restriction of immune response is still unclear. Co
      inhibitory immune checkpoints are important molecules which could negatively
      modulate immune response especially in T cell function. In this study we detected
      the expressional pattern of PD-1/LAG-3 in periapical lesions. Immunohistochemical
      staining showed that the inflammatory response including up-regulation of TNF
      alpha and the infiltration of T cells, was severe in granuloma and restricted in
      periapical cyst. PD-1 and LAG-3 both could be detected in granuloma and cyst,
      while scarcely observed in control group. Exhausted T cells, characterized by PD
      1 or LAG-3 positive, accumulated within granuloma and reduced in cyst. Our study
      revealed that in periapical lesions, T cell exhaustion characterized by PD-1 or
      LAG-3 positive, might contribute to the auto-restriction of inflammatory response
      in periapical lesions.

PMID- 30210705
TI  - Radiofrequency ablation plus nucleotide analogous for hepatitis B virus-related
      hepatocellular carcinoma: a cost-effectiveness analysis.
AB  - In the real-world, it is unclear that after the radiofrequency ablation (RFA),
      whether it is a cost-effective strategy to administer nucleotide analogue (NA)
      for patients with hepatitis B virus (HBV)-related HCC patients. The aim of this
      study was to estimate the cost-effectiveness of the RFA plus NA versus RFA alone
      in patients with HBV-related HCC within the Milan criteria in China and the USA.
      A Markov model was developed to simulate a cohort of patients with HCC within the
      Milan criteria and Child-Pugh A/B cirrhosis and underwent RFA with or without NA
      therapy over their remaining life expectancy. Analysis was performed in two
      geographical cost settings: China and the USA. The RFA plus NA therapy provided
      an average of 7.57 years, whereas RFA monotherapy offered 5.83 years. The RFA
      plus NA therapy produced 5.09 quality-adjusted life years (QALYs), whereas RFA
      monotherapy achieved 3.89 QALYs. The incremental cost-effectiveness ratio (ICER)
      of the RFA plus NA therapy versus RFA monotherapy was $10368.19/QALY in China and
      $38805.45/QALY in the USA. These values were below the thresholds of the cost
      effectiveness in both countries. Sensitivity analysis revealed that the utility
      of recurrent HCC was the most sensitive parameter in all cost scenarios in both
      of the RFA plus NA therapy and RFA monotherapy groups. Our Markov model has shown
      that for the patients with HBV-related HCC within the Milan criteria and Child
      Pugh A/B cirrhosis, RFA plus NA is more cost-effective than RFA monotherapy
      across the two different cost scenarios namely, China and the USA.

PMID- 30210707
TI  - Low expression of the long non-coding RNA NR_026827 in gastric cancer.
AB  - AIM: The contribution of long non-coding RNAs (lncRNAs) to gastric cancer
      associated with Helicobacter pylori (H. pylori) infection remains largely
      unknown. Therefore, the present study aimed to investigate the expression of a
      lncRNA NR_026827 in gastric epithelial cells infected with H. pylori, and
      demonstrate its expression characteristic in gastric cancer. MATERIALS AND
      METHODS: Gastric epithelial cell line cells, GES-1, were cultured and infected
      with H. pylori. A microarray was used to analyze the lncRNA profile of gastric
      epithelial cells. Eighty fresh gastric cancer tissues and the paired adjacent non
      cancerous tissue samples were randomly selected from patients. The expression of
      the lncRNA NR_026827 was investigated using quantitative real-time polymerase
      chain reaction (qRT-PCR). RESULTS: The expression of several lncRNAs was
      significantly altered in GES-1 cells following infection with H. pylori. Of these
      lncRNAs, NR_026827 was dramatically down-regulated in GES-1 cells infected with
      H. pylori. In addition, the expression of NR_026827 was decreased in gastric
      cancer tissues in comparison to the corresponding adjacent non-cancerous tissues.
      Moreover, the expression of NR_026827 did not change significantly in different
      gastric cancer stages. CONCLUSION: The lncRNA, NR_026827, is down-regulated in
      all stages of gastric cancer associated with H. pylori infection and could
      represent a potential biomarker for the diagnosis of gastric cancer.

PMID- 30210706
TI  - Endometrial progesterone receptor isoforms in women with polycystic ovary
      syndrome.
AB  - CONTEXT: Polycystic ovary syndrome (PCOS) affects approximately 4%-18% of all
      reproductive-aged women and is often accompanied by endometrial progesterone (P4)
      resistance. Endometrial cells from PCOS patients display increased progesterone
      receptor (PGR) expression; however, in vivo knockout studies and in vitro
      experiments indicate the two PGR isoforms are not functionally equivalent.
      OBJECTIVE: We aimed to compare endometrial PGR isoform expression between non
      PCOS and PCOS patients during the proliferative phase. DESIGN: A case-control
      study. The expression of PGR isoforms (PGRA and PGRB), estrogen receptor alpha
      (ERalpha), and markers of cell proliferation was determined by qRT-PCR, Western
      blot, immunohistochemistry, and immunofluorescence assays. PATIENT(S): Patients
      were recruited and diagnosed with PCOS according to the Rotterdam criteria
      provided by the American Society for Reproductive Medicine and the European
      Society for Human Reproduction and Embryology. Endometrial biopsy samples were
      collected from non-PCOS patients with regular menstrual cycles or with
      hyperplasia (n = 11) and from PCOS patients with or without hyperplasia (n = 14).
      RESULT(S): Although the alteration of PGRB mRNA and protein expression was
      different, we found that PGRA mRNA and protein expression was higher in PCOS
      patients than non-PCOS patients. PGRA/B and PGRB were localized in both
      epithelial and stromal cells, with notable changes in the nuclei of epithelial
      and stromal cells. A similar expression pattern of ERalpha, vimentin and Ki-67,
      in association with an increased PGR expression, was observed in PCOS patients.
      CONCLUSION(S): These results demonstrated that elevated both PGR isoform
      expression depends on the presence of PCOS, and our data suggest that abnormal
      regulation of PGR isoforms is a pathological outcome of defective endometrium in
      PCOS patients.

PMID- 30210709
TI  - Association between circulating fibrocytes and angiographic coronary collaterals
      in patients with obstructive coronary artery disease.
AB  - Circulating fibrocytes are a population of bone marrow-derived progenitor cells
      that have been implicated in neovascularization. The recruitment of coronary
      artery collaterals, a form of neovascularization, is associated with improved
      outcomes in coronary artery disease. In this study, we tested the hypothesis
      that, in subjects with stable chronic coronary artery disease, the blood
      concentration of fibrocytes is associated with the presence of angiographic
      coronary collaterals. A total of 58 subjects with at least one epicardial
      coronary artery with >= 90% luminal stenosis were enrolled, among whom 26 (45%)
      had angiographic evidence of coronary collaterals. Subjects with collaterals had
      significantly elevated circulating concentrations of all examined subsets of
      activated fibrocytes, suggesting that there is a relationship between fibrocytes
      and coronary collateral recruitment.

PMID- 30210708
TI  - Role of platelet alpha2-adrenoreceptor in biological low response to Clopidogrel
      for patients with non cardioembolic ischemic stroke or transient ischemic attack.
AB  - BACKGROUND AND PURPOSE: Low biological response to Clopidogrel prescribed after
      non cardioembolic ischemic stroke or transient ischemic attack (TIA) is a major
      clinical problem and could explain the recurrence of vascular events. Platelet
      alpha2-adrenoreceptors are involved in the high residual platelet reactivity in
      stable coronary artery disease patients on dual antiplatelet therapy. In the
      present study we investigated the impact of platelet alpha2-adrenoreceptors on
      ADP-induced platelet aggregation and on ADP-induced platelet membrane CD62P (P
      selectin) expression, a marker of platelet activation on blood samples from
      patients hospitalized at the acute phase of a non cardioembolic ischemic stroke
      or TIA. METHODS: 72 consecutive patients were prospectively recruited over the
      course of two years in a monocentric study. Patients received a daily 75 mg-dose
      of Clopidogrel. ADP-induced platelet aggregation was measured alone, with low
      dose epinephrine or with atipamezole, a selective alpha blocker of alpha2
      adrenoreceptors, by Light Transmittance Aggregometry (LTA). Platelet membrane
      expression of P-selectin was measured by flow cytometry with either ADP alone or
      combined with epinephrine. RESULTS: Epinephrine at low dose stimulated ADP
      induced platelet membrane expression of CD62P whereas Atipamezole significantly
      inhibited 10 uM ADP-induced platelet aggregation. CONCLUSIONS: Our study showed
      the role of platelet alpha2-adrenoreceptors in biological low response to
      Clopidogrel for patients hospitalized for a non-cardioembolic ischemic stroke or
      TIA. Atipamezole could improve the status of biological response to Clopidogrel.

PMID- 30210710
TI  - BRAF mutation in papillary thyroid carcinoma (PTC) and its association with
      clinicopathological features and systemic inflammation response index (SIRI).
AB  - The aim of the present research was to investigate the association between the
      BRAF mutation and papillary thyroid carcinoma (PTC), and further explore the
      relationship between the systemic inflammation response index (SIRI) and BRAF
      mutation in patients with PTC. The clinicopathological data were extracted from
      the patients' medical records from June 2012 to June 2014 in our hospital. We
      enrolled 95 patients with PTC that have received the total or near-total
      thyroidectomy and pretracheal and paratracheal lymph node dissection. The blood
      samples were obtained before surgery. According to the BRAF mutation analysis,
      the patients were divided into two groups: BRAF mutation positive group and BRAF
      mutation negative group. The receiver operating characteristic curve (ROC) for
      the presence of BRAF mutation was used to evaluate the optimal cutoff value of
      SIRI. The ratio closest to the point with maximum sensitivity and specificity was
      defined as the optimal cutoff value. Univariate and multivariate logistic
      regression model were used to confirm the independent factors and compare
      observed and predicted outcomes. The BRAF mutation rates were 62.1% (59/95). The
      results indicated that BRAF mutation was significantly correlated with
      pathological TNM stage, monocyte, SIRI and Galectin-3. The pathological TNM
      stage, monocyte, SIRI and Galectin-3 were the significant risk factors associated
      with the presence of BRAF mutation. Moreover, we found that patients with low
      SIRI had higher BRAF mutation percentage than those with high SIRI, and patients
      with low monocyte had higher percentage than those with high monocyte. BRAF
      mutation is associated with the pathological TNM stage, monocyte, SIRI and
      Galectin-3, and SIRI was the significant risk factor with the BRAF mutation and
      patients with low SIRI have higher BRAF mutation.

PMID- 30210712
TI  - Erratum: COUP-TFII promotes colorectal carcinoma resistance to doxorubicin
      involving inhibition of epithelial-mesenchymal transition.
AB  - [This corrects the article on p. 3921 in vol. 8, PMID: 27725871.].

PMID- 30210713
TI  - Hypertension in Oman: Where Do We Stand?

PMID- 30210711
TI  - 1,25(OH)2D3 suppresses proinflammatory responses by inhibiting Th1 cell
      differentiation and cytokine production through the JAK/STAT pathway.
AB  - 1,25(OH)2D3 is an immune modulation hormone with beneficial effects on T cell-
      mediated autoimmune diseases. The purpose of the present study is to investigate
      the direct effects of vitamin D on Bacillus Calmette Guerin (BCG)-infected CD4+ T
      cells in both VDR-deficient (VDR-/-) mice and wild type (WT) mice. Specifically,
      we aimed to investigate the effect of vitamin D on Th1 cells and elucidate the
      underlying molecular mechanism. Naive CD4 T cells were purified from VDR-/- mice
      and WT mice to induce Th1 cells and were activated by BCG. Th1 cell
      differentiation and cytokine production in vitro were inhibited by 10 nM
      1,25(OH)2D3. The JAK/STAT pathway was activated by 1,25(OH)2D3 addition in both
      VDR-/- and wild type T cells. In vivo, a vitamin D-deficiency VDR-/- and WT mouse
      model was established and the mice were vaccinated with BCG. An ELISA assay was
      performed to measure the levels of VD, IL-2, IFN-gamma and TNF-beta in the blood,
      and flow cytometry was used to analyze the proportion of Th1 and Th2 cells in the
      spleen. 1,25(OH)2D3 affected Th cells polarization by inhibiting Th1 and
      augmenting Th2 cell development in the vitamin D-deficiency mouse model.
      Moreover, 1,25(OH)2D3 inhibited the inflammatory infiltrates and expression of IL
      2, IFN-gamma and TNF-beta in the spleen of vitamin D-deficient mice following
      vaccination with BCG. These findings suggested that 1,25(OH)2D3 suppressed the
      inflammatory response by inhibiting Th1 cell differentiation and cytokine
      production by the JAK/STAT pathway.

PMID- 30210714
TI  - Implementation of Digital Health Technology at Academic Medical Centers in Saudi
      Arabia.
AB  - Academic Medical Centers (AMCs) in Saudi Arabia are dedicated to providing high
      quality patient care and promoting the health and wellbeing of its citizens.
      Additionally, they provide medical education and conduct research in a wide range
      of clinical disciplines. A recent global trend in academic hospitals with
      mandates similar to those in Saudi Arabia is that they have started utilizing
      digital health technology in a bid to increase efficiency and improve the quality
      of patient care. This paper takes the position that such digital health
      technologies should also be utilized in AMC settings in Saudi Arabia. Electronic
      health records (EHRs), smartphones, video-imaging technologies, virtual desktop
      infrastructures, mobile EHR access, and smart-beds can help AMCs serve patients
      more effectively. Rural people can be connected to consultants at AMCs using
      these technologies using virtual self-care tools. Validation of new digital
      health devices can be performed in collaboration with digital health partners and
      serve to enrich the knowledge of medical students in the area of digital health.
      This review aims to draw the attention of stakeholders to the need to implement
      digital health technology in AMCs in Saudi Arabia and help improve the quality of
      healthcare.

PMID- 30210715
TI  - Upper Tract Imaging in Patients with Initial or Terminal Hematuria Suggestive of
      Bleeding from the Lower Urinary Tract: How Often is the Upper Urinary Tract
      Responsible for the Hematuria?
AB  - Objectives: Visible hematuria (VH) is a common urological complaint. A history of
      initial or terminal VH in men is indicative of a lower urinary tract (LUT)
      source. A careful clinical history could limit unnecessary extensive upper tract
      imaging in this group of patients with VH. We conducted a single-center
      prospective study to examine the usefulness of investigating the upper tract in
      patients with a history of VH likely from a LUT source (initial and/or terminal
      VH) with specific reference to the incidence of demonstrable significant upper
      tract abnormalities. Methods: We conducted a single-center prospective study of
      consecutive male patients presenting with VH over eight months. All patients
      underwent standard investigations including physical examination, flexible
      cystoscopy (FC), and radiological imaging (ultrasound scan (USS) and/or computed
      tomography urogram (CTU)). Those with a clear history of initial or terminal VH
      were identified for further scrutiny with regards to detectable upper tracts
      abnormalities. Results: In total, 57 patients (aged 23-95 years) with initial or
      terminal VH were identified. Of these, 56 had FC and nine patients were
      subsequently diagnosed with a LUT malignancy. With regards to upper urinary tract
      (UUT), 35 patients (61.4%) had an USS, 46 (80.7%) underwent a CTU, and 25 (43.9%)
      patients had both. In this group, no UUT malignancy was identified on upper tract
      imaging. Conclusions: Initial or terminal VH patients may not need extensive
      upper tract imaging. FC is recommended, but a non-invasive USS can be a safe
      initial investigation for the UUT, with a CTU subsequently considered in those
      with abnormalities on USS and those with ongoing bleeding. Further combined
      multicenter analysis will help corroborate these findings and could have several
      beneficial outcomes including a reduction in investigations cost, patient
      inconvenience, and ionizing radiation.

PMID- 30210716
TI  - Value of Ultrasound in the Detection of Benign and Malignant Breast Diseases: A
      Diagnostic Accuracy Study.
AB  - Objectives: We sought to determine the diagnostic accuracy of ultrasound for
      benign and malignant breast lesions. Methods: This retrospective study was
      performed to evaluate the diagnostic accuracy of ultrasound in 203 patients with
      complete medical records who visited Mehr Medical Imaging Center for breast
      ultrasound between March 2014 and February 2016. The collected data comprised of
      demographic characteristics, ultrasound results (consisting of the anatomic area
      of the lesion, the involved side, and the ultrasound characteristics of the
      lesion), mammogram results, and pathology reports (if surgery or biopsy was
      performed). Results: For the diagnosis of malignant and benign lesions,
      ultrasound had a sensitivity of 93.9% and specificity of 86.5%; its positive and
      negative predictive values were 86.9% and 93.8%, respectively. Lesion type was
      significantly associated with a family history of breast cancer and fertility
      status (p < 0.005), but there was no significant association between the involved
      side and tumor type (p > 0.050). Conclusions: Mammography is the best technique
      for screening and identifying patients with non-mass-like breast lesions and
      microcalcifications. Considering the false positive and false-negative results,
      ultrasound is not a perfect screening modality. Future studies are recommended to
      study the value of ultrasound in the detection of high-risk breast cancer
      patients.

PMID- 30210717
TI  - Occurrence of Hypothyroidism, Diabetes Mellitus, and Celiac Disease in Emirati
      Children with Down's Syndrome.
AB  - Objectives: Autoimmune diseases are known to occur in people with Down's syndrome
      (DS), especially celiac disease, type 1 diabetes mellitus (DM), and
      hypothyroidism. Since there are common genetic risk factors involved in the
      occurrence of these autoimmune disorders, the risks would differ in different
      populations. We sought to determine the prevalence of type 1 DM, celiac disease,
      and hypothyroidism in Emirati patients with DS in Abu Dhabi, UAE. Methods: Ninety
      two patients with DS were investigated for the presence of anti-thyroid
      antibodies, antithyroglobulin, and anti-thyroid peroxidase antibodies for
      hypothyroidism, anti-glutamic acid decarboxylase antibodies for type 1 DM, and
      anti-tissue transglutaminase immunoglobulin A antibodies for celiac disease.
      Results: Karyotyping was performed on 89 patients. Eighty-seven had non
      disjunction of chromosome 21 (97.8%), one was a mosaic, and one had
      translocation. Of the patients studied, 19.6% had hypothyroidism, 4.3% had type 1
      DM, and 1.1% had celiac disease. Out of the 92 patients studied, 66 (71.7%) did
      not have any autoimmune disease, 25 (27.2%) had one autoimmune disease, and one
      (1.1%) had two autoimmune diseases. Conclusions: Celiac disease was the least
      prevalent autoimmune disease in patients with DS patients, while type 1 DM and
      hypothyroidism were both significantly associated with DS.

PMID- 30210718
TI  - Correlation Between beta-Glucan and Neutrophil/Eosinophil Ratio of Paranasal
      Sinus Mucosa and Blood in the Diagnosis of Chronic Fungal Rhinosinusitis.
AB  - Objectives: Chronic fungal rhinosinusitis is a major health problem because of
      the large impact on quality of life and difficult medical treatment. Its
      prevalence is increasing. There is currently an opportunity to establish the
      diagnosis without invasive intervention by utilizing beta-glucan, which is the
      largest component of fungal cell wall and neutrophil/eosinophil ratio (NER). We
      sought to discover the correlation between beta-glucan level and the NER of
      paranasal sinuses mucosa and blood as a potential diagnostic marker for patients
      with chronic fungal rhinosinusitis. Methods: We conducted a cross-sectional study
      involving 20 subjects. Blood sampling and maxillary sinus surgery were performed,
      and fungal identification in the sinus mucosa was determined using the polymerase
      chain reaction. If a fungal species with beta-glucan was found, then the
      examination was continued with the measurement of beta-glucan by enzyme-linked
      immunosorbent assay, neutrophil, and eosinophil flow cytometry in sinus mucosa
      and blood. Results: Aspergillus flavus is the most commonly found fungus. All
      subjects passed the positive beta-glucan limit (3 80 pg/mL) of the mucosal sample
      and only one subject had intermediate results (60-79 pg/mL) from their blood
      sample. Seventeen subjects had mucosal eosinophilic inflammation whereas the
      blood of 12 subjects revealed neutrophilic inflammation. There was no significant
      difference between the level of beta-glucan in blood and mucosal sinus (p =
      0.886), so that beta-glucan examination of blood can describe beta-glucan levels
      in paranasal sinuses. There was a significant difference between mucosal NER and
      blood (p < 0.001). beta-glucan level with NER in both paranasal sinus mucosa and
      blood had no significant correlation (p > 0.050). Conclusions: beta-glucan can be
      used to establish the diagnosis of chronic fungal rhinosinusitis. However,
      differential diagnosis of allergy or infection cannot be excluded by examination
      of blood NER. Still, it is hoped that the process of diagnosis can be obtained
      quickly and precisely without the need for invasive procedure although it
      requires more research, especially related to the diagnostic test.

PMID- 30210719
TI  - The Association of a Rare Variant of -93, -53 Promoter Gene Polymorphisms of
      Lipoprotein Lipase gene with Obesity and Insulin Resistance.
AB  - Objectives: Obesity increases the risk of numerous chronic diseases. Obesity is
      classified clinically using body mass index (BMI), waist-to-hip ratio, and body
      fat percentage. The lipoprotein lipase (LPL) gene has been linked to lipoprotein
      metabolism and obesity. We performed a case-control study to determine the
      association between LPL gene polymorphisms and obesity-associated phenotypes such
      as insulin resistance (IR). Methods: We examined the different LPL gene variants
      for association in 642 individuals segregated by BMI and IR. Genotyping of the
      LPL gene -93 and -53 promoter gene polymorphisms were analyzed using polymerase
      chain reaction-restriction fragment length polymorphism. Results: A substantial
      association was observed for -93 gene polymorphism of the LPL gene with obesity,
      while -53 promoter gene polymorphism showed association with IR. Conclusions: We
      found a significant association between -93 and -53 promoter gene polymorphisms
      of the LPL gene with obesity and associated phenotypes in the studied population.

PMID- 30210720
TI  - Prevalence, Risk Factors, and Fetal and Maternal Outcomes of Hypertensive
      Disorders of Pregnancy: A Retrospective Study in Western Saudi Arabia.
AB  - Objectives: We sought to estimate the prevalence of hypertensive disorders of
      pregnancy (HDP) in Saudi Arabia as well as the risk factors of HDP, and maternal
      and fetal outcomes. Methods: We retrospectively evaluated the medical records of
      9493 women who delivered at King Abdulaziz University Hospital, a tertiary care
      center, between January 2015 and June 2017. All cases of HDP were included.
      Results: We identified 224 pregnant women with HDP in our patient cohort, giving
      a prevalence of 2.4%. Their mean age was 31.3+/-6.7 years, with an average
      gravidity of 4.0 and average parity of 3.0. The most prevalent subtype of HDP was
      preeclampsia (54.9%) while 29.5% of the women had gestational hypertension, and
      8.0% had eclampsia. The prevalence of subtypes of HDP differed significantly with
      gravidity, and mean age differed significantly with HDP subtype. Personal and
      family histories of preeclampsia and the presence of diabetes were more prevalent
      in women with preeclampsia and gestational hypertension; however, only the
      difference in diabetes prevalence was significant. The overall prevalence of
      maternal complications was 9.4% and the prevalence of maternal mortality was
      1.3%. Multigravid women and women with chronic hypertension were at increased
      risk of prematurity compared to other pregnant women, but not significantly.
      Conclusions: The prevalence of HDP was relatively low in our cohort. However, to
      prevent harmful impacts on both the mother and fetus, screening for this disorder
      is recommended early in pregnancy.

PMID- 30210721
TI  - Level of Satisfaction on Service Quality Dimensions Based on SERVQUAL Model Among
      Patients Attending 1 Malaysia Clinic in Kota Bharu, Malaysia.
AB  - Objectives: Implemented in 2010, 1 Malaysia Clinic (1MC) is the latest innovation
      in public primary healthcare services in Malaysia to serve the urban population.
      This study aimed to assess the level of satisfaction and its associated factors
      using the SERVQUAL (SERV-service, QUAL-quality) instrument. We also sought to
      compare the difference of mean score between expectation and perception of
      SERVQUAL dimension among patients attending 1MC in Kota Bharu district, Malaysia.
      Methods: This cross-sectional study included all nine 1MCs in the Kota Bharu
      district, Malaysia, and used the validated SERVQUAL questionnaire from Ministry
      of Health, Malaysia. The primary data was collected in January 2017. The sample
      size was proportionate to the average daily patient attendance for each clinic,
      and a simple random sampling method was applied to reduced selection bias.
      Satisfaction level was determined by the mean gap score of expectation and
      perception of the SERVQUAL dimension. Results: A total of 386 patients were
      involved in this study (184 male and 202 female). Most were from the low
      socioeconomic group. Less than half of the patients were satisfied with the
      clinic services. The tangible dimension (service quality (SQ) gap: -0.25) was the
      most critical dimension among all five SQ dimensions assessed. The factors
      included low education level (adjusted odds ratio (adj. OR) 1.87; 95% confidence
      interval (CI): 1.06, 2.67; p = 0.024), monthly household income less than RM 3000
      (adj. OR 2.97; 95% CI: 1.72, 5.51; p < 0.001), and frequency 3 3 visits (adj. OR
      2.23; 95% CI: 1.44, 3.45; p < 0.001) had significant association with high level
      of satisfaction. Conclusion: 1MC has achieved its objective to increase the
      accessibility of health services among the low-income population in urban
      settings. However, most patients were not satisfied with certain parts of the
      services. Thus, proper evaluation of the service gap is required for improvement
      of the service.

PMID- 30210722
TI  - Improving Student's Self-Efficacy and Perceived Susceptibility Toward Oral and
      Dental Health: A Randomized Controlled Trial.
AB  - Objectives: We sought to assess the impact of educational intervention on female
      junior high school students' perceived susceptibility and self-efficacy regarding
      oral and dental health. Methods: We recruited 100 female junior high school
      students (50 in intervention and 50 in control group) from Falavarjan city using
      multistage random sampling. A self-administered questionnaire was used to gather
      data about study variables. Students in the intervention group attended five 90
      minute sessions designed to teach the students about dental hygiene. Results: We
      found no significant difference between the two groups with respect to the
      preintervention mean scores of knowledge, perceived susceptibility, and self
      efficacy (p > 0.050). The postintervention mean scores in the intervention group
      were significantly higher than those in the control group (p < 0.050).
      Conclusions: Training plans with particular behavioral goals and good
      instructional strategies can be useful in empowering students toward dental
      health.

PMID- 30210723
TI  - Autosomal Dominant Polycystic Kidney Disease and Pericardial Effusion.
AB  - The autosomal dominant polycystic kidney disease (ADPKD) accounts for one out of
      400-1000 live births, being a hereditary disorder with cystic and noncystic
      manifestations as well as extrarenal involvement. The pericardial effusion (PE)
      in the context of a patient with ADPKD is complex, and it is not entirely
      defined. Several theories have been proposed. The most accepted, so far, is
      linked to mutations in the PKD1 gene which can entail an abnormal production of
      matrix components, matrix-degrading enzymes, and inhibitors of
      metalloproteinases, and defects in connective tissue which would lead to an
      abnormal distensibility of the connective tissue. We report the case of a 35-year
      old female Moroccan patient with the diagnosis of ADPKD associated with arterial
      hypertension who came into the Emergency Department with lower abdominal pain
      lasting for five days being diagnosed as salpingitis. Abdominal computed
      tomography scan with contrast showed both kidneys with several cystic images with
      a thin wall. A transthoracic echocardiogram revealed the presence of moderate PE
      more in the anterior aspect. A greater set of standard tests to rule out collagen
      vascular disease, rheumatoid diseases, autoimmune disorders, and malignancies was
      ordered. These tests yielded no abnormality. The association of ADPKD with PE is
      rare. The awareness of this connection by the emergency physicians is key to
      prevent misplaced concern.

PMID- 30210724
TI  - Severe Nodulocystic Acne not Responding to Isotretinoin Therapy Successfully
      Treated with Oral Dapsone.
AB  - Nodulocystic acne is a severe form of acne which can result in significant damage
      to the skin with great impact on quality of life. Oral isotretinoin considered to
      be the best treatment for such cases. Although it has a high rate of success and
      its efficacy is well established in the treatment of nodulocystic acne, it may
      occasionally fail to control the disease. We report a case of a patient who
      presented to our skin clinic with severe facial nodulocystic acne in which
      treatment with isotretinoin failed to achieve disease control and caused
      worsening of his baseline condition. Therefore, oral dapsone was administered as
      an alternative treatment, and we reached a complete remission of acne lesions
      within six months. Oral dapsone could be an adequate and safe drug in severe
      acne, and it might also be a promising and hopeful alternative treatment for
      nodulocystic acne when isotretinoin fails.

PMID- 30210725
TI  - The Tip of the Iceberg in Maternally Inherited Diabetes and Deafness.
AB  - Maternally inherited diabetes and deafness (MIDD) is not only a disorder of the
      pancreas and ears but a multisystem mitochondrial disorder syndrome.
      Hypogonadism, however, has not been reported as a phenotypic feature of MIDD. We
      report a single case of a patient with MIDD which manifested clinically at 41
      years old. In addition to diabetes and deafness, he manifested with seizures,
      ataxia, myopathy, and hypogonadism. We used established methods for the routine
      workup of this patient. MIDD is indeed a multisystem condition. A previously
      undescribed phenotypic feature of MIDD may be hypogonadism.

PMID- 30210726
TI  - Laparoscopic Management of a Torsioned Round Ligament Fibroid.
AB  - Round ligament fibroids are rare tumors and can present as inguinal, adnexal, or
      vulvar masses. Preoperative diagnosis can be made by ultrasonography or magnetic
      resonance imaging (MRI). A 28-year-old virgin female presented with pelvic pain
      that persisted for a few days. Her sonographic evaluation detected a well-defined
      hyperechoic 45 * 40 mm right adnexal mass interfering endometrioma. A contrast
      enhanced pelvic MRI showed a 43 * 39 * 32 mm solid mass located in the right
      adnexa. Laparoscopic exploration revealed a well-defined double torsion around
      the peduncle pinky solid mass arising from the right round ligament. The mass was
      resected with the final histopathological diagnosis being leiomyoma. The
      diagnosis of round ligament fibroids can be challenging, and laparoscopy is one
      of the first options where surgical facilities are available.

PMID- 30210727
TI  - Imaging Pitfalls of the Acutely Traumatized Pediatric Elbow.

PMID- 30210728
TI  - How to Discriminate Between Primary Hepatic Lymphoma and Cholangiocarcinoma.

PMID- 30210729
TI  - The pathologic and diagnostic in magnetic resonance imaging of brain and cervical
      spine of patients with neuromyelitis optica spectrum disorder.
AB  - Background: Neuromyelitis optica spectrum disease (NMOSD) is a chronic
      inflammatory demyelinating disorder that involves central nervous system (CNS)
      with high affinity for involvement of optic nerve and spinal cord. In current
      study, due to high prevalence of NMOSD in Isfahan, Iran, we have aimed to assess
      brain and spine magnetic resonance imaging (MRI) of patients with NMOSD. Methods:
      This cross-sectional study was performed on 62 patients with diagnosis of NMOSD,
      who referred to MS clinic of Kashani hospital, Isfahan City, during 2015-17.
      Patients' age, age of onset, primary brain and spine MRI findings, and expanded
      disability status scale (EDSS) were recorded in check list. Patients underwent
      new brain and spine MRI. Data were analyzed with SPSS software. Descriptive data
      were reported by mean +/- standard deviation (SD). Results: 62 known cases of
      NMOSD including 9 (14.5%) men and 53 (85.5%) women with mean age of 34.32 +/-
      10.26 years, mean age of onset of 28.03 +/- 12.09 years, and mean EDSS of 2.63 +/
      1.55 were assessed. 33.9% of patients were anti-neuromyelitis optica (NMO)
      antibody seropositive. Longitudinal extensive transverse myelitis (LETM) and
      segmental spinal lesions were found in 66.1% and 29.0% of patients, respectively.
      Diagnostic NMO brain lesions and posterior periventricular lesions were seen in
      38.7% and 67.7% of patients, respectively. Two patients had tumefactive lesions.
      Conclusion: In current study, we found high rate of posterior periventricular
      lesions in brain MRI and segmental lesions in spine MRI of both anti-NMO antibody
      seropositive and seronegative patients. As these lesions are not in NMOSD
      diagnosis criteria, more considerations are recommended. In addition, tumefactive
      lesions in patients with NMOSD were an exciting finding of this study that should
      be discussed about more.

PMID- 30210730
TI  - Evaluation of the risk of cervical cancer in patients with Multiple Sclerosis
      treated with cytotoxic agents: A cohort study.
AB  - Background: Since most patients with relapsing-remitting multiple sclerosis
      (RRMS) are women, the present study aimed to determine whether treatment of
      patients with MS by cytotoxic agents is associated with an increased risk of
      cervical dysplasia. Cancer screening is often neglected in the chronic diseases
      such as MS, so more attention in this field was needed. Decreasing morbidity and
      mortality due to cervical cancer is the most important goal of screening in
      female MS patients especially in child bearing age. Thus, it can be said that
      this is the first study which investigated this important issue. Methods: A total
      of 129 individuals participated in this cohort study. They were assigned into 3
      groups including 43 patients with MS who were treated with cytotoxic drugs, 43
      patients with MS on immunomodulators, and 43 normal healthy controls. Pap smears
      were performed following standard methods and the results obtained from the three
      groups were compared by statistical analysis. Demographic data, Expanded
      Disability Status Scale (EDSS), and Pap smear changes were analyzed by SPSS
      software. Results: The most commonly detected abnormality in all examined
      patients and healthy controls was inflammation. Five patients with MS who were
      treated with cytotoxic agents revealed benign cellular changes (BCC) in their Pap
      smear that were statistically significant in comparison with other groups (P =
      0.03). Patients who took Mitoxantrone presented BCC more than other groups [Odds
      ratio (OR) = 9.44, 95% confidence interval (CI): 1.46-60.70]. There was no
      significant difference between mean duration of MS diagnosis (P = 0.12), mean
      duration of previous MS treatments (P = 0.25), and mean duration of current MS
      treatments (P = 0.21) in patients with BCC compared to normal healthy controls or
      inflammatory change. Conclusion: According to the results of present study, BCC
      is more frequently observed in patients with MS who were treated with cytotoxic
      agents with immunosuppressive effect. Since BCC is a 'premalignant condition',
      the authors suggest that mandatory annual Pap smear should be performed for
      patients with MS who are treated with cytotoxic agents irrespective of their age
      in order to detect early signs of malignancy.

PMID- 30210731
TI  - Serum leptin levels in Iranian patients with Parkinson's disease.
AB  - Background: Parkinson's disease (PD), the second most prevalent neurodegenerative
      disorder, has been related with weight loss and energy balance. Some studies
      showed that leptin might be playing an important role in satiety, energy balance
      and immune response. The aim of this study was to evaluate serum leptin level in
      patients with PD and its association with clinical severity. Methods: In this
      cross-sectional study, 35 patients with PD and 51 healthy controls (HCs), matched
      for age, sex and body mass index (BMI), were recruited. Serum leptin level was
      measured and clinical characteristics and demographic data of patients were
      recorded. Results: The mean age of patients with PD and HCs were 59.80 +/- 11.40
      and 62.18 +/- 11.60 years, respectively. Serum leptin concentration was not
      statistically different between patients with PD and HCs (21.1 +/- 23.1 ng/ml vs
      25.9 +/- 21.8 ng/ml, P = 0.280). There was no relation between plasma level of
      leptin and clinical severity of patients with PD. Conclusion: Our findings
      suggest that serum level of leptin is neither implicated in the pathogenesis of
      PD, nor decreases as disease progresses.

PMID- 30210732
TI  - Evaluating the relationship between emotional intelligence and cognitive
      disorders in patients with Multiple Sclerosis.
AB  - Background: Emotional intelligence refers to a process through which an
      individual is not only capable of understanding his/her/others' emotions, but
      also is able to manage them. Emotional intelligence can get disturbed due to
      different neurological diseases. Since cognition and emotion are directly and
      closely related, the present study aims to evaluate the relationship between
      emotional intelligence and cognitive disorders in patients with Multiple
      Sclerosis (MS). Methods: The demographic data of 92 MS patients participating in
      this study were recorded. The emotional intelligence and cognitive disorders were
      studied using the Bradberry-Greaves, and MS Neuropsychological Questionnaire
      (MSNQ) tests, respectively. Results: 16 men and 76 women were considered in this
      study. The mean age of the participants was 33.4 years, the mean duration of the
      disease was 6.8 years, the mean of Expanded Disability Status Scale (EDSS) was
      1.97, the mean MSNQ was 21.58, and the mean emotional quotient (EQ) of the
      patients was 74.18. The MSNQ had a significant relationship with the total EQ and
      its sub-categories (P < 0.05). Conclusion: This study showed that EQ and
      cognitive disorders are directly relevant to each other; as cognitive disorder
      increases, the EQ rate decreases. Therefore, cognitive rehabilitation might be
      effective in enhancing the EQ in these patients.

PMID- 30210733
TI  - Investigating related factors with mortality rate in patients with postoperative
      meningitis: One longitudinal follow up study in Iran.
AB  - Background: Postoperative meningitis (POM) is the most dreaded cause of morbidity
      and mortality in neurosurgery patients. This study aimed to identify incidence
      and mortality rate as well as related factors to outcome in patients with POM.
      Methods: This descriptive longitudinal study conducted on patients with POM in
      duration of 2 years. Incidence and mortality rates as well as related factors
      were studied. Results: The incidence and mortality rates of POM was 8.9% and 50%,
      respectively. There were statistically significant association between male
      gender, as well as having mechanical ventilation, and death outcome in
      univariable analysis. In addition, in multivariable logistic regression analysis,
      length of intensive care unit (ICU) stay of more than 7 days [Odds ratio (OR):
      1.2, confidence interval of 95% (95%CI): 1.02-6.2), mechanical ventilation (OR:
      1.1, 95%CI: 1.05-5.1], positive cerebrospinal fluid (CSF) culture (OR: 2.4,
      95%CI: 1.9-4.08) were predicting factors to death outcome. Finally, we found an
      inverse relationship between survival function and length of ICU stay in patients
      with POM. Conclusion: According to the high rates of incidence and mortality due
      to POM in this study, preventive studies to decrease this dreaded cause of
      morbidity and mortality in neurosurgery patients should be the planned.

PMID- 30210734
TI  - Doege-Potter syndrome: When seizures and hypoglycemia collide.

PMID- 30210736
TI  - Interferon beta-1b-induced thrombotic thrombocytopenic purpura-hemolytic uremic
      syndrome (TTP-HUS) in a patient treated for multiple sclerosis: A case report.

PMID- 30210735
TI  - Thrombotic microangiopathy associated with interferon-beta treatment in patients
      with multiple sclerosis.

PMID- 30210737
TI  - Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes
      (POEMS) syndrome complicated by ischemic stroke: A case report.

PMID- 30210738
TI  - Unilateral internal carotid artery agenesis: Correct diagnosis using computed
      tomography (CT) scan.

PMID- 30210739
TI  - The Effect of Educational Program Based on Belief, Attitude, Subjective Norm, and
      Enabling Factors Model on Changing the Metabolic Indices in Elderly Patients with
      Type II Diabetes.
AB  - Background: Diabetes is the most common disease related to metabolism disorders.
      Today, diabetes in the elderly is one of the major epidemics of the century. This
      study aimed to investigate the effect of nutrition and jogging-based Belief,
      Attitude, Subjective Norm, and Enabling Factors (BASNEF) model in changes in
      metabolic parameters that performed in elderly patients with type II diabetes in
      Fasa city. Methods: This study was a randomized clinical trial on 108 elderly
      patients with type II diabetes (54 patients in the experimental group and 54 in
      control group) referred to the diabetes center in Fasa City, Fars Province, Iran,
      in 2016. Data were collected using a valid self-reported questionnaire including
      demographic variables and BASNEF Model (knowledge, attitudes, subjective norms,
      and enabling factors), checklist for patient's practices nutrition and jogging
      based on self-reporting patients, assess the level of fasting blood sugar (FBS),
      low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides
      (TG), and HbAlc patients which was completed by both groups before and 3 months
      after the intervention. The experimental group received the training in eight
      sessions; each session lasted for 70 min. Then, the data were entered into the
      SPSS 22 software (SPSS Inc., IBM, Chicago, IL, USA) and were analyzed using
      descriptive statistics, Chi-square test, independent t-test, and paired t-test. P
      <0.05 was considered as statistically significant. Results: The results showed
      that the mean scores of the BASNEF components (knowledge, attitudes, subjective
      norms, and enabling factors) in two experimental and control groups after
      intervention were a significant difference. After training program, nutritional
      and jogging performance in the experimental group was better than the control
      group. Furthermore, FBS (P < 0.001), LDL (P < 0.001), HDL (P < 0.001), TG (P <
      0.001), and HbAlc (P < 0.001) improved significantly in the experimental group
      compared to the control group. Conclusions: Plan and implement nutrition and
      jogging education using the BASNEF model to improve metabolic parameters in
      diabetic patients are very effective and beneficial. Moreover, in the
      implementation of these programs, control, monitoring, and follow-up educational
      are recommended.

PMID- 30210740
TI  - Hemophagocytic Lymphohistiocytosis in Adults: Low Incidence of Primary Neoplasm
      as a Trigger in a Case Series from Turkey.
AB  - Hemophagocytic Lymphohistiocytosis (HLH) is an indicator of an exaggerated immune
      response and eventually adverse outcomes. This study aimed to investigate the
      clinical and laboratory features and outcomes of patients with HLH. The medical
      records of 26 HLH adult patients (>= 16 years of age) were retrospectively
      analyzed. Gender, age, the duration of fever, time to diagnosis, etiology and
      laboratory data were extracted from the records. The mean age was 38 +/- 18
      years, and 15 (58%) patients were female. A total of nine cases had infectious
      diseases; four cases had rheumatologic diseases, three cases had hematological
      malignancies while nine cases could not have a definitive diagnosis. The median
      time to detection of HLH was 20 days (IQR: 8-30 d). Of the 25 patients, 11 (44%)
      died. The erythrocyte sedimentation rates of the surviving and non-surviving
      patients were 39 +/- 22 mm/h and 15 +/- 13 mm/h, respectively. When a long
      lasting fever is complicated by bicytopenia or pancytopenia (especially),
      clinicians should promptly consider the possibility of HLH syndrome to improve
      patients' prognosis.

PMID- 30210742
TI  - Transient Elastography (TE) is a Useful Tool for Assessing the Response of Liver
      Iron Chelation in Sickle Cell Disease Patients.
AB  - Sickle cell disease patients often need regular blood transfusions to improve
      both the quality of life and survival from the veno-occlusive complications of
      the disease. Deferasirox, a convenient long acting oral agent, has recently been
      introduced in clinical practice with promising efficacy. This study aims to
      evaluate the association of liver stiffness and possible fibrosis with iron
      deposition and confirm the use of elastography as a validated test of responding
      to chelation with low cost and easy access. 15 patients with sickle cell disease
      and systemic or occasional transfusions were evaluated with MRI, transient
      elastography and biochemistry, for liver iron(LIC) and liver stiffness(LSM)
      before onset and one year after taking Deferasirox. All patients completed the
      study. Our results showed improvement in hepatic iron and hepatic stiffness after
      chelation therapy; Furthermore ALT, AST, LDH and ferritin levels have improved
      after 12 months of therapy with deferasirox. During the study no serious adverse
      events were encountered indicating the safety of the drug. Transient liver
      elastography findings correlate with serum ferritin and LIC in patients with
      sickle cell disease and it is a useful tool for assessing the response of liver
      iron chelation therapy.

PMID- 30210743
TI  - Epidemiology of Malaria in the State of Qatar, 2008-2015.
AB  - Background and Objectives: Imported malaria poses a serious public health problem
      in Qatar because its population is "naive" to such infection; where local
      transmission might lead to serious, life-threatening infection and might even
      trigger epidemics. Methods: This study is a retrospective review of the imported
      malaria cases in Qatar reported by the malaria surveillance program at the
      Ministry of Public Health (MoPH), during the period between January 2008 and
      December 2015. All cases were imported and underwent parasitological confirmation
      through microscopy. Results: A total of 4092 malaria cases were reported during
      2008-2015 in Qatar. The demographic features of the imported cases show that the
      majority of cases were males (93%), non-Qatari (99.6%), and aged 15 to 44 years
      (82.1%). Moreover, P. vivax was found to be the main etiologic agent accounting
      for more than three-quarters (78.7%) of the imported cases. In addition, almost a
      third (33.1%) of the cases were reported during the months of July, August, and
      September. Conclusions: Imported malaria in Qatar has witnessed an increase
      during the past seven years, despite a long period of constant reduction; where
      the people most affected were adult male migrants from endemic countries. Many
      challenges need to be overcome to prevent the reintroduction of malaria into the
      country.

PMID- 30210744
TI  - Outbreak of Burkholderia Cepacia Infection: a Systematic Study in a
      Hematolooncology Unit of a Tertiary Care Hospital from Eastern India.
AB  - Background: Burkholderia cepacia, an aerobic gram-negative bacillus, is a
      frequent colonizer of fluids used in the hospital ward. It poses little risk of
      infection to healthy people; however it is a known important opportunistic
      pathogen causing morbidity and mortality due to its intrinsic resistance to most
      of the antibiotics in hospitalized patients. Small hospital outbreaks are
      frequent. B. cepacia may occur as an opportunistic infection in hemato-oncology
      patients. Here we present an outbreak of Burkholderia cepacia infection in
      hematology ward of our institute. Methods: Febrile episodes as defined by IDSA
      guideline, 2010 were followed, and blood for culture and sensitivity was sent in
      all the events. The culture was done by an automated method using Bactalert 3d
      Biomeriux & sensitivity pattern by Microscan Siemens method and subsequently
      detected by PCR based method. Results: During September 2016 to February 2017
      (six months), a total of 498 blood cultures were sent during febrile episodes.
      Out of which 60 (12%) came out to be positive for different microorganisms. Out
      of all positive cultures, Burkholderia cepacia was detected in 29 (48%) patients,
      which reduced drastically following the change in antibiotic administration
      practice. All isolates showed sensitivity to pipercillin+tazobactum,
      cefoperazone+sulbactum, fluoroquinolones, cotrimoxazole and carbapenems and
      resistance to polymyxin B and colistin. With timely intervention by appropriate
      intravenous antibiotics as per culture sensitivity result and change in
      antibiotic preparation practice, overall mortality was low 1 (4%) out of 29
      culture positive episodes. Conclusion: Change of antibiotic preparation practice
      was the key to control this outbreak, and overall mortality was low.

PMID- 30210745
TI  - The Spectrum of Hypereosinophilia and Associated Clonal Disorders - A Real-World
      Data Based on Combined Retrospective and Prospective Analysis from a Tropical
      Setting.
AB  - Objective: To determine the frequency, etiological spectrum and treatment outcome
      of hypereosinophilia (HE) and hypereosinophilic syndromes (HES) in a tropical
      setting. Methods: A retrospective analysis of hospital data of five years
      (January 2009 to December 2013) and a comprehensive prospective evaluation of
      patients presenting with HE/HES over a period of 33 months (January 2014 to
      September 2016) was performed. Results: HE/HES was diagnosed in a total of 125
      patients during the study period with an estimated prevalence of 0.5-1 case per
      100,000 population in our hospital settings. 41 patients were excluded from the
      final analysis due to lack of sufficient data. Infections, especially helminths
      were the commonest cause (34%) followed by primary/clonal HE/HES (24%) and
      reactive HE/HES secondary to various clonal disorders (14.3%). A lymphocytic
      variant of HES and FIP1L1-PDGFRA positive HES were diagnosed in 3.6% each.
      Imatinib-responsive BCR-ABL1 negative HE/HES constitute 7.1% in our patients.
      None of the clinical or routine laboratory features including the age of
      patients, duration of HE, presence or absence of organomegaly, hemoglobin levels,
      eosinophil %, absolute eosinophil count, total leukocyte count, platelet counts,
      serum IgE levels or presence of myelofibrosis could predict or exclude malignancy
      in patients with HE/HES. The absence of blasts in peripheral blood or the absence
      of >5% blasts in bone marrow does not exclude primary/clonal HES. Conclusions: An
      underlying malignancy (Primary HE/HES and neoplasms leading to reactive HES;
      35.7%) is diagnosed with nearly equal frequency compared to infections (34.5%) in
      tropical settings. There are no hematological or serological parameters, which
      can reliably be used to exclude an underlying malignancy, necessitating a
      thorough follow-up and comprehensive work-up in patients with HE/HES.

PMID- 30210741
TI  - Invasive Aspergillosis in Children: Update on Current Guidelines.
AB  - Invasive aspergillosis (IA) is an important cause of infectious morbidity and
      mortality in immunocompromised paediatric patients. Despite improvements in
      diagnosis, prevention, and treatment, IA is still associated with high mortality
      rates. To address this issue, several international societies and organisations
      have proposed guidelines for the management of IA in the paediatric population.
      In this article, we review current recommendations of the Infectious Diseases
      Society of America, the European Conference on Infection in Leukaemia and the
      European Society of Clinical Microbiology and Infectious Diseases for the
      management and prevention of IA in children.

PMID- 30210746
TI  - Molecular Characterization of Vancomycin, Mupirocin and Antiseptic Resistant
      Staphylococcus aureus Strains.
AB  - Background: Staphylococcus aureus is a common cause of nosocomial infections
      leading to a broad spectrum of diseases. Increasing antibiotic resistance among
      S. aureus strains, particularly methicillin-resistant S. aureus (MRSA), is a
      serious concern. In addition, the emergence of antiseptics resistance in MRSA
      helps the organism to persist and spread in healthcare environments easily. The
      aim of this study was to determine the molecular characteristics of vancomycin,
      mupirocin, and antiseptic resistant S. aureus strains. Materials and Methods:
      This cross-sectional study was performed on a total of 120 MRSA isolates
      collected from two major hospitals in Shiraz, Iran. Minimum inhibitory
      concentrations (MICs) of vancomycin and mupirocin were determined by E-test
      method according to CLSI and Eucast guidelines. Presence of resistance genes was
      investigated by PCR method. Results: Antibacterial susceptibility tests for MRSA
      isolates showed that three isolates (2.5%) were vancomycin-intermediate S. aureus
      (VISA), seven isolates (5.8%) were vancomycin-resistant S. aureus (VRSA), and 15
      isolates (12.5%) were high-level mupirocin-resistant (MuH). None of the isolates
      had vancomycin resistance gene (vanA), but the frequency of mupirocin resistance
      gene was significant, and 55 (45.8%) isolates carried the mupA gene. Moreover,
      norA, smr and qacA/B genes were detected in 110 (91.7%), 55 (45.8%) and 36 (30%)
      strains, respectively. Conclusion: This study showed the existence of VISA and
      VRSA strains in our region, and we also found a high frequency of mupirocin and
      biocide resistance genes among them.

PMID- 30210747
TI  - Prevalence of Thalassemia among Newborns: A Re-visited after 20 Years of a
      Prevention and Control Program in Northeast Thailand.
AB  - Background: To provide accurate prevalence information of thalassemia in
      northeast Thailand, authors performed thalassemia screening in newborns after 20
      years implementation of a prevention and control program. Methods: Study was done
      on 350 cord blood specimens collected consecutively at Maternal and Child
      Hospital, Regional Health Promotion Center 7, Khon Kaen, Thailand. All kinds of
      alpha- and beta-thalassemias were identified using combined hemoglobin (Hb) and
      DNA analyses. Results: Among 350 newborns examined, subjects with thalassemia
      genes were identified in 184 (52.6%) cases with as many as 22 different
      genotypes. The most prevalent one was Hb E (39.1%). The incidence of 3.1% alpha0
      thalassemia, 25.9% alpha+-thalassemia, 5.4% Hb Constant Spring and 1.4% of Hb
      Pakse were encountered. Heterozygous beta-thalassemia was found in 2 cases
      (0.6%). Hb capillary electrophoresis could demonstrate Hb E in all cases with Hb
      E and detected different levels of Hb Bart's for different alpha-thalassemia
      genotypes but not in all cases with alpha-thalassemia. No newborn with severe
      thalassemia diseases was encountered. Conclusion: This study reveals that alpha
      thalassemia, beta-thalassemia, and Hb E carriers as well as complex thalassemia
      syndromes are still prevalence and indicates a need for continuing a prevention
      and control program in the region.

PMID- 30210748
TI  - The Emerging Resistance in Nosocomial Urinary Tract Infections: From the
      Pediatrics Perspective.
AB  - Background: Healthcare-associated infections results in increased health care
      costs and mortality. There are limited studies concerning the distribution of the
      etiologic agents and the resistance patterns of the microorganisms causing
      healthcare-associated urinary tract infections (HA-UTI) in pediatric settings.
      Objectives: The aim of this study was to evaluate the distribution and antibiotic
      susceptibility patterns of pathogens causing HA-UTI in children. Material and
      Methods: Isolates from 138 children with UTI who were hospitalized in pediatric,
      neonatal and pediatric surgery intensive care units were reviewed. Results: Most
      common isolated organism was Klebsiella pneumoniae (34.1%) and Escherichia coli
      (26.8%). Among the Pseudomonas aeruginosa, Meropenem and imipenem resistance
      rates were 46.2% and 38.5%. Extended-spectrum beta-lactamase (ESBL) production
      was present in 48 Klebsiella species (82.8%). Among ESBL positive Klebsiella
      species, the rate of meropenem and imipenem resistance was 18.8%, and ertapenem
      resistance was 45.9%. Extended spectrum beta-lactamase production was present in
      27 (72.9%) Escherichia coli species. Among ESBL positive E. coli, the rate of
      meropenem and imipenem resistance was 7.4%, and ertapenem resistance was 14.8.
      Conclusions: Emerging meropenem resistance in P. aeruginosa, higher rates of
      ertapenem resistance in ESBL positive ones in E. coli and Klebsiella species in
      pediatric nosocomial UTI are important notifying signs for superbug infections.

PMID- 30210751
TI  - Biomechanics and Bioengineering of Orthopedic and Cardiovascular Rehabilitation.

PMID- 30210750
TI  - Peripheral Nervous System Involvement in Lymphoproliferative Disorders.
AB  - Peripheral neuropathies are a vast group of diseases with heterogeneous
      aetiologies, including genetic and acquired causes. Several haematological
      disorders may cause an impairment of the peripheral nervous system, with diverse
      mechanisms and variable clinical, electrophysiological and pathological
      manifestations. In this practical review, we considered the main phenotypes of
      peripheral nervous system diseases associated with lymphoproliferative disorders.
      The area of intersection of neurological and haematological fields is of
      particular complexity and raises specific problems in the clinical practice of
      lymphoproliferative disorders. The personal crosstalk between neurologists and
      haematologists remains a fundamental tool for a proper diagnostic process which
      may lead to successful treatments in most cases.

PMID- 30210749
TI  - Mutational Profiles of F8 and F9 in a Cohort of Haemophilia A and Haemophilia B
      Patients in the Multi-ethnic Malaysian Population.
AB  - Background: Haemophilia A (HA) and Haemophilia B (HB) are X-linked blood
      disorders that are caused by various mutations in the factor VIII (F8) and factor
      IX (F9) genes respectively. Identification of mutations is essential as some of
      the mutations are associated with the development of inhibitors. This study is
      the first comprehensive study of the F8 mutational profile in Malaysia. Materials
      and methods: We analysed 100 unrelated HA and 15 unrelated HB patients for
      genetic alterations in the F8 and F9 genes by using the long-range PCR, DNA
      sequencing, and the multiplex-ligation-dependent probe amplification assays. The
      prediction software was used to confirm the effects of these mutations on factor
      VIII and IX proteins. Results: 44 (53%) of the severe HA patients were positive
      for F8 intron 22 inversion, and three (3.6%) were positive for intron one
      inversion. There were 22 novel mutations in F8, including missense (8),
      frameshift (9), splice site (3), large deletion (1) and nonsense (1) mutations.
      In HB patients, four novel mutations were identified including the splice site
      (1), small deletion (1), large deletion (1) and missense (1) mutation.
      Discussion: The mutational spectrum of F8 in Malaysian patients is heterogeneous,
      with a slightly higher frequency of intron 22 inversion in these severe HA
      patients when compared to other Asian populations. Identification of these
      mutational profiles in F8 and F9 genes among Malaysian patients will provide a
      useful reference for the early detection and diagnosis of HA and HB in the
      Malaysian population.

PMID- 30210752
TI  - Improvement of Adequate Digoxin Dosage: An Application of Machine Learning
      Approach.
AB  - Digoxin is a high-alert medication because of its narrow therapeutic range and
      high drug-to-drug interactions (DDIs). Approximately 50% of digoxin toxicity
      cases are preventable, which motivated us to improve the treatment outcomes of
      digoxin. The objective of this study is to apply machine learning techniques to
      predict the appropriateness of initial digoxin dosage. A total of 307 inpatients
      who had their conditions treated with digoxin between 2004 and 2013 at a medical
      center in Taiwan were collected in the study. Ten independent variables,
      including demographic information, laboratory data, and whether the patients had
      CHF were also noted. A patient with serum digoxin concentration being controlled
      at 0.5-0.9 ng/mL after his/her initial digoxin dosage was defined as having an
      appropriate use of digoxin; otherwise, a patient was defined as having an
      inappropriate use of digoxin. Weka 3.7.3, an open source machine learning
      software, was adopted to develop prediction models. Six machine learning
      techniques were considered, including decision tree (C4.5), k-nearest neighbors
      (kNN), classification and regression tree (CART), randomForest (RF), multilayer
      perceptron (MLP), and logistic regression (LGR). In the non-DDI group, the area
      under ROC curve (AUC) of RF (0.912) was excellent, followed by that of MLP
      (0.813), CART (0.791), and C4.5 (0.784); the remaining classifiers performed
      poorly. For the DDI group, the AUC of RF (0.892) was the best, followed by CART
      (0.795), MLP (0.777), and C4.5 (0.774); the other classifiers' performances were
      less than ideal. The decision tree-based approaches and MLP exhibited markedly
      superior accuracy performance, regardless of DDI status. Although digoxin is a
      high-alert medication, its initial dose can be accurately determined by using
      data mining techniques such as decision tree-based and MLP approaches. Developing
      a dosage decision support system may serve as a supplementary tool for clinicians
      and also increase drug safety in clinical practice.

PMID- 30210754
TI  - Leveraging JAK-STAT regulation in myelofibrosis to improve outcomes with
      allogeneic hematopoietic stem-cell transplant.
AB  - Primary myelofibrosis (PMF) is a disease characterized by bone marrow fibrosis,
      extramedullary hematopoiesis, risk of transformation to acute myeloid leukemia,
      and a substantial symptom burden with diminished quality of life. Allogeneic
      hematopoietic cell transplantation (HCT) is the only curative option; however,
      disease relapse and graft versus host disease (GVHD) are significant barriers to
      long-term survival. The discovery of the JAK2 V617F mutation, and subsequent
      development of JAK inhibitors, resulted in improved survival and significant
      improvements in spleen volumes and symptom scores. Though the effect of JAK
      inhibition on transplant outcome is poorly understood, using JAK inhibition to
      achieve maximal response prior to HCT is standard practice at major centers.
      After allogeneic HCT, a significant proportion of patients with steroid
      refractory GVHD have clinical responses to JAK inhibition. Targeting this pathway
      is a key component in the management of patients with PMF before and after
      allogeneic HCT.

PMID- 30210755
TI  - Update on the role of brentuximab vedotin in classical Hodgkin lymphoma.
AB  - Brentuximab vedotin (BV) is an effective and well-tolerated treatment for
      patients with classical Hodgkin lymphoma (HL). It was initially approved by the
      US FDA for the treatment of HL after failure of autologous hematopoietic stem
      cell transplant (autoHSCT) or after failure of at least two prior lines of
      multiagent chemotherapy in patients who are not transplant candidates, and then
      subsequently, as consolidation therapy after autoHSCT in patients who are at high
      risk for relapse. However, the role of BV in the treatment of HL is evolving. BV
      has shown promising efficacy as a salvage treatment in the second-line setting
      prior to autoHSCT. Most recently, the ECHELON-1 trial demonstrated that BV
      combined with AVD for the treatment of newly diagnosed advanced stage HL improved
      modified progression-free survival (mPFS) compared with standard ABVD. Based on
      these results, the US FDA has approved BV as part of the initial treatment of
      advanced stage HL. With the approval of BV as front-line therapy, depending on
      how widely the use of BV plus AVD is adopted, the role of BV in the treatment of
      patients with relapsed or refractory (rel/ref) HL may need to be redefined. BV
      retreatment can be effective, and studies of rational BV-based combination
      regimens may help to improve response rates and overcome BV resistance.
      Furthermore, BV has been demonstrated to be effective in the initial treatment of
      elderly or unfit patients, and ongoing studies are evaluating the addition of BV
      to initial chemotherapy in patients with early stage HL.

PMID- 30210753
TI  - The Cell Research Trends of Asthma: A Stem Frequency Analysis of the Literature.
AB  - Objective: This study summarized asthma literature indexed in the Medical
      Literature Analysis and Retrieval System Online (MEDLINE) and explored the
      history and present trends of asthma cell research by stem frequency ranking to
      forecast the prospect of future work. Methods: Literature was obtained from
      MEDLINE for the past 30 years and divided into three groups by decade as the
      retrieval time. The frequency of stemmed words in each group was calculated using
      Python with Apache Spark and the Natural Language Tool Kit for ranking. The
      unique stems or shared stems of 3 decades were summarized. Results: A total of
      1331, 4393, and 7215 records were retrieved from 3 decades chronologically, and
      the stem ranking of the top 50 were listed by frequency. The number of stems
      shared with 3 decades was 26 and with the first and last 2 decades was 5 and 13.
      Conclusions: The number of cell research studies of asthma has increased rapidly,
      and scholars have paid more attentions on experimental research, especially on
      mechanistic research. Eosinophils, mast cells, and T cells are the hot spots of
      immunocyte research, while epithelia and smooth muscle cells are the hot spots of
      structural cell research. The research trend is closely linked with the
      development of experimental technology, including animal models. Early studies
      featured basic research, but immunity research has dominated in recent decades.
      The distinct definition of asthma phenotypes associated with genetic
      characteristics, immunity research, and the introduction of new cells will be the
      hot spots in future work.

PMID- 30210758
TI  - Correction: Ligand survey results in identification of PNP pincer complexes of
      iridium as long-lived and chemoselective catalysts for dehydrogenative borylation
      of terminal alkynes.
AB  - [This corrects the article DOI: 10.1039/C5SC02161H.].

PMID- 30210759
TI  - Correction: Assessing the exchange coupling in binuclear lanthanide(iii)
      complexes and the slow relaxation of the magnetization in the
      antiferromagnetically coupled Dy2 derivative.
AB  - [This corrects the article DOI: 10.1039/C5SC01029B.].

PMID- 30210756
TI  - Gene therapy for hemophilia: what does the future hold?
AB  - Recent phase I/II adeno-associated viral vector-mediated gene therapy clinical
      trials have reported remarkable success in ameliorating disease phenotype in
      hemophilia A and B. These trials, which highlight the challenges overcome through
      decades of preclinical and first in human clinical studies, have generated
      considerable excitement for patients and caregivers alike. Optimization of vector
      and transgene expression has significantly improved the ability to achieve
      therapeutic factor levels in these subjects. Long-term follow-up studies will
      guide standardization of the approach with respect to the combination of
      serotype, promoter, dose, and manufacturing processes and inform safety for
      inclusion of young patients. Certain limitations preclude universal applicability
      of gene therapy, including transient liver transaminase elevations due to the
      immune responses to vector capsids or as yet undefined mechanisms, underlying
      liver disease from iatrogenic viral hepatitis, and neutralizing antibodies to
      clotting factors. Integrating vectors show promising preclinical results, but
      manufacturing and safety concerns still remain. The prospect of gene editing for
      correction of the underlying mutation is on the horizon with considerable
      potential. Herein, we review the advances and limitations that have resulted in
      these recent successful clinical trials and outline avenues that will allow for
      broader applicability of gene therapy.

PMID- 30210757
TI  - Practical aspects of extended half-life products for the treatment of
      haemophilia.
AB  - Haemophilia A and haemophilia B are congenital X-linked bleeding disorders caused
      by deficiency of coagulation factor VIII (FVIII) and IX (FIX), respectively. The
      preferred treatment option for patients with haemophilia is replacement therapy.
      For patients with severe disease, prophylactic replacement of coagulation factor
      is the treatment of choice; this has been shown to reduce arthropathy
      significantly, reduce the frequency of bleeds and improve patients' quality of
      life. Prophylaxis with standard recombinant factor requires regular intravenous
      infusion at least two (FIX) to three (FVIII) times a week. Recombinant FVIII and
      FIX products with an extended half-life are in development, or have been recently
      licensed. With reported mean half-life extensions of 1.5-1.8 times that of
      standard products for FVIII and 3-5 times that of standard products for FIX,
      these products have the potential to address many of the unmet needs of patients
      currently treated with standard factor concentrates. For example, they may
      encourage patients to switch from on-demand treatment to prophylaxis and improve
      the quality of life of patients receiving prophylaxis. Indeed, extended half-life
      products have the potential to reduce the burden of frequent intravenous
      injections, reducing the need for central venous lines in children, promote
      adherence, improve outcomes, potentially allow for more active lifestyles and,
      depending on the dosing regimen, increase factor trough levels. Members of the
      Zurich Haemophilia Forum convened for their 19th meeting to discuss the
      practicalities of incorporating new treatments into the management of people with
      haemophilia. This review of extended half-life products considers their
      introduction in haemophilia treatment, including the appropriate dose and
      schedule of infusions, laboratory monitoring, patient selection, safety
      considerations, and the economic aspects of care.

PMID- 30210761
TI  - Outstanding Reviewers for Chemical Science in 2017.
AB  - We would like to take this opportunity to highlight the Outstanding Reviewers for
      Chemical Science in 2017, as selected by the editorial team for their significant
      contribution to the journal.

PMID- 30210760
TI  - Second-order nonlinear optical switching with a record-high contrast for a
      photochromic and thermochromic bistable crystal.
AB  - Nonlinear optical (NLO) switchable materials are important for photonic and
      optoelectronic technologies. One important issue for NLO photoswitching, the most
      studied physical switching approach, is how to improve the switching contrast of
      second harmonic generation (SHG) in crystals, because the known values are
      generally below 3 times. Thermoswitching, as another approach, has shown
      impressive high SHG-switching contrasts (4-infinity times), but the fast decay of
      thermally induced states demands constant heat sources to maintain specific SHG
      intensities. We have synthesized a photochromic and thermochromic bistable
      acentric compound, beta-[(MQ)ZnCl3] (MQ+ = N-methyl-4,4'-bipyridinium), which
      represents the first crystalline compound with both photo- and heat-induced SHG
      switching behavior and the first example of a thermoswitchable NLO crystal that
      can maintain its expected second-order NLO intensity without any heat source. The
      SHG-switching contrast can reach about 8 times after laser irradiation or 2 times
      after thermal annealing. The former value is the highest recorded for
      photoswitchable NLO crystals. This work also indicates that higher SHG-switching
      contrasts may be obtained through increasing electron-transfer efficiency,
      variation of permanent dipole moment, and self-absorption.

PMID- 30210762
TI  - Double enhancement of hydrogen storage capacity of Pd nanoparticles by 20 at%
      replacement with Ir; systematic control of hydrogen storage in Pd-M nanoparticles
      (M = Ir, Pt, Au).
AB  - We report on binary solid-solution nanoparticles (NPs) composed of Pd and Ir,
      which are not miscible at the equilibrium state of the bulk, for the first time,
      by means of a process of hydrogen absorption/desorption from core (Pd)/shell (Ir)
      NPs. Only 20 at% replacement with Ir atoms doubled the hydrogen-storage
      capability compared to Pd NPs, which are a representative hydrogen-storage
      material. Furthermore, the systematic control of hydrogen concentrations and the
      corresponding pressure in Pd and Pd-M NPs (M = Ir, Pt, Au) have been achieved
      based on the band filling control of Pd NPs.

PMID- 30210763
TI  - Facile access to deep red/near-infrared emissive AIEgens for efficient non-doped
      OLEDs.
AB  - Notwithstanding the huge demand in bio-imaging and optoelectronics, the
      construction of highly emissive deep red/near infrared (DR/NIR) organic
      luminogens is still a big challenge because a narrow energy gap generally leads
      to low photoluminescence quantum yield. It is even more difficult to afford
      DR/NIR emitters in the solid state due to the aggregation caused quenching (ACQ)
      effect. In this work, we found that the direct attachment of a
      tetraphenylethylene substituted arylamine to the electron accepting 2,1,3
      benzothiadiazole produces DR/NIR AIE luminogens with bright emission facilely and
      efficiently. And the emission wavelengths could be tuned from the red to the
      DR/NIR region by regulating the variety of the substituents. The long emission
      wavelength and high photoluminescence quantum yield of these AIEgens are ascribed
      to the effective intramolecular charge transfer and the suppressed intramolecular
      motion. Furthermore, non-doped OLEDs based on one of the AIEgens showed an EL
      emission at 684 nm with a large radiance of 5772 mW Sr-1 m-2 and an impressive
      external quantum efficiency (EQE) of 1.73%.

PMID- 30210764
TI  - O2-3-Aminopropyl diazeniumdiolates suppress the progression of highly metastatic
      triple-negative breast cancer by inhibition of microvesicle formation via nitric
      oxide-based epigenetic regulation.
AB  - Currently, there is no effective therapy for the treatment of highly metastatic
      triple-negative breast cancer (TNBC). Microvesicle (MV) formation is crucial for
      the metastasis of TNBC. Here we report a novel strategy to inhibit the generation
      of MVs for the intervention of TNBC. O2-3-Aminopropyl diazeniumdiolates 3a-f are
      designed and synthesized, which can be activated by lysyloxidase over-expressed
      in TNBC cells. The most active compound 3f is able to selectively release high
      levels of NO in TNBC cells, inhibit the cell proliferation, and reduce the
      adhesion, invasion and migration of TNBC cells in vitro. Furthermore, 3f
      significantly suppresses the growth and metastasis of implanted TNBC in vivo
      through attenuating MV formation by an epigenetic modification of miR-203/RAB22A
      expression in an NO-dependent manner, providing the first evidence of NO donor(s)
      acting as epigenetic modulators to fight highly metastatic TNBC.

PMID- 30210765
TI  - Hydrogen-bonded perylene bisimide J-aggregate aqua material.
AB  - A new twelvefold methoxy-triethyleneglycol-jacketed tetraphenoxy-perylene
      bisimide (MEG-PBI) amphiphile was synthesized that self-assembles into two types
      of supramolecular aggregates in water: red-coloured aggregates of low order and
      with weak exciton coupling among the PBIs and blue-coloured strongly coupled J
      aggregates consisting of a highly ordered hydrogen-bonded triple helix of PBIs.
      At room temperature this PBI is miscible with water at any proportions which
      enables the development of robust dye aggregates in solution, in hydrogel states
      and in lyotropic liquid crystalline states. In the presence of 60-95 wt% water,
      self-standing coloured hydrogels exhibit colour changes from red to blue
      accompanied by a fluorescence light-up in the far-red region upon heating in the
      range of 30-50  degrees C. This phenomenon is triggered by an entropically driven
      temperature-induced hydrogen-bond-directed slipped stacking arrangement of the
      MEG-PBI chromophores within structurally well-defined J-aggregates. This
      versatile aqua material is the first example of a stable PBI J-aggregate in
      water. We anticipate that this study will open a new avenue for the development
      of biocompatible functional materials based on self-assembled dyes and inspire
      the construction of other hydrogen-bonded supramolecular materials in the highly
      competitive solvent water.

PMID- 30210766
TI  - Combining traditional 2D and modern physical organic-derived descriptors to
      predict enhanced enantioselectivity for the key aza-Michael conjugate addition in
      the synthesis of PrevymisTM (letermovir).
AB  - Quantitative structure-activity relationships have an extensive history for
      optimizing drug candidates, yet they have only recently been applied in reaction
      development. In this report, the predictive power of multivariate
      parameterization has been explored toward the optimization of a catalyst
      promoting an aza-Michael conjugate addition for the asymmetric synthesis of
      letermovir. A hybrid approach combining 2D QSAR and modern 3D physical organic
      parameters performed better than either approach in isolation. Using these
      predictive models, a series of new catalysts were identified, which catalyzed the
      reaction to provide the desired product in improved enantioselectivity relative
      to the parent catalyst.

PMID- 30210767
TI  - Divergent ring-opening coupling between cyclopropanols and alkynes under cobalt
      catalysis.
AB  - Cobalt-diphosphine catalysts promote ring-opening coupling reactions between
      cyclopropanols and unactivated internal alkynes, affording either beta-alkenyl
      ketones or multisubstituted cyclopentenol derivatives in good yields with good to
      excellent regioselectivities. The chemoselectivity between these beta
      alkenylation and [3 + 2] annulation reactions, which likely share a cobalt
      homoenolate as a key catalytic intermediate, is exquisitely controlled by the
      reaction conditions, with the solvent being a major controlling factor. The
      reactions are proposed to involve ring opening of cobalt cyclopropoxide into
      homoenolate, migratory insertion of the alkyne into the Co-C bond, and
      protodemetalation or intramolecular carbonyl addition of the resulting
      alkenylcobalt species. The feasibility of these reaction steps was supported by
      DFT calculations.

PMID- 30210769
TI  - A mononuclear nonheme {FeNO}6 complex: synthesis and structural and spectroscopic
      characterization.
AB  - While the synthesis and characterization of {FeNO}7,8,9 complexes have been well
      documented in heme and nonheme iron models, {FeNO}6 complexes have been less
      clearly understood. Herein, we report the synthesis and structural and
      spectroscopic characterization of mononuclear nonheme {FeNO}6 and iron(iii)
      nitrito complexes bearing a tetraamido macrocyclic ligand (TAML), such as
      [(TAML)FeIII(NO)]- and [(TAML)FeIII(NO2)]2-, respectively. First, direct addition
      of NO(g) to [FeIII(TAML)]- results in the formation of [(TAML)FeIII(NO)]-, which
      is sensitive to moisture and air. The spectroscopic data of [(TAML)FeIII(NO)]-,
      such as 1H nuclear magnetic resonance and X-ray absorption spectroscopies,
      combined with computational study suggest the neutral nature of nitric oxide with
      a diamagnetic Fe center (S = 0). We also provide alternative pathways for the
      generation of [(TAML)FeIII(NO)]-, such as the iron-nitrite reduction triggered by
      protonation in the presence of ferrocene, which acts as an electron donor, and
      the photochemical iron-nitrite reduction. To the best of our knowledge, the
      present study reports the first photochemical nitrite reduction in nonheme iron
      models.

PMID- 30210768
TI  - Nanowell-mediated two-dimensional liquid chromatography enables deep proteome
      profiling of <1000 mammalian cells.
AB  - Multidimensional peptide separations can greatly increase the depth of coverage
      in proteome profiling. However, a major challenge for multidimensional
      separations is the requirement of large biological samples, often containing
      milligram amounts of protein. We have developed nanowell-mediated two-dimensional
      (2D) reversed-phase nanoflow liquid chromatography (LC) separations for in-depth
      proteome profiling of low-nanogram samples. Peptides are first separated using
      high-pH LC and the effluent is concatenated into 4 or 12 nanowells. The contents
      of each nanowell are reconstituted in LC buffer and collected for subsequent
      separation and analysis by low-pH nanoLC-MS/MS. The nanowell platform minimizes
      peptide losses to surfaces in offline 2D LC fractionation, enabling >5800
      proteins to be confidently identified from just 50 ng of HeLa digest.
      Furthermore, in combination with a recently developed nanowell-based sample
      preparation workflow, we demonstrated deep proteome profiling of >6000 protein
      groups from small populations of cells, including ~650 HeLa cells and 10 single
      human pancreatic islet thin sections (~1000 cells) from a pre-symptomatic type 1
      diabetic donor.

PMID- 30210772
TI  - Rapid, non-invasive characterization of the dispersity of emulsions via
      microwaves.
AB  - A rapid and non-invasive method to determine the dispersity of emulsions is
      developed based on the interrelationship between the droplet size distribution
      and the dielectric properties of emulsions. A range of water-in-oil emulsions
      with different water contents and droplet size distributions were analysed using
      a microwave cavity perturbation technique together with dynamic light scattering.
      The results demonstrate that the dielectric properties, as measured by non
      invasive microwave cavity analysis, can be used to characterise the dispersity of
      emulsions, and is also capable of characterizing heavy oil emulsions. This
      technique has great potential for industrial applications to examine the
      sedimentation, creaming and hence the stability of emulsions.

PMID- 30210770
TI  - Quasi-single-crystalline CoO hexagrams with abundant defects for highly efficient
      electrocatalytic water oxidation.
AB  - Defects and structural long-range ordering have been recognized as two crucial
      characters for advanced electrocatalysts. However, these two features have rarely
      been achieved together. Herein, we report the preparation of single-crystalline
      CoO hexagrams and demonstrate their exceptional electrocatalytic properties for
      water oxidation. The quasi-single-crystalline CoO hexagrams, prepared at the
      critical phase transition point of beta-Co(OH)2/Co(OH)F hexagrams, possess both
      abundant oxygen vacancies as defects and structural long-range ordering. The
      matching between the b-axis of Co(OH)F crystals and the a-axis of beta-Co(OH)2
      crystals is critical for the formation of the CoO hexagram single crystals. The
      quasi-single-crystalline CoO hexagrams with abundant defects are highly efficient
      for water oxidation by delivering a 10 mA cm-2 current density at a low
      overpotential of 269 mV in a 1 M KOH aqueous solution.

PMID- 30210773
TI  - A simple, label-free, electrochemical DNA parity generator/checker for error
      detection during data transmission based on "aptamer-nanoclaw"-modulated protein
      steric hindrance.
AB  - Versatile DNA logic devices have exhibited magical power in molecular-level
      computing and data processing. During any type of data transmission, the
      appearance of erroneous bits (which have severe impacts on normal computing) is
      unavoidable. Luckily, the erroneous bits can be detected via placing a parity
      generator (pG) at the sending module and a parity checker (pC) at the receiving
      module. However, all current DNA pG/pC systems use optical signals as outputs. In
      comparison, sensitive, facilely operated, electric-powered electrochemical
      outputs possess inherent advantages in terms of potential practicability and
      future integration with semiconductor transistors. Herein, taking an even pG/pC
      as a model device, we construct the first electrochemical DNA pG/pC system so
      far. Innovatively, a thrombin aptamer is integrated into the input-strand and it
      functions as a "nanoclaw" to selectively capture thrombin; the electrochemical
      impedance changes induced by the "nanoclaw/thrombin" complex are used as label
      free outputs. Notably, this system is simple and can be operated within 2 h,
      which is comparable with previous fluorescent ones, but avoids the high-cost
      labeled-fluorophore and tedious nanoquencher. Moreover, taking non-interfering
      poly-T strands as additional inputs, a cascade logic circuit (OR-2 to 1 encoder)
      and a parity checker that could distinguish even/odd numbers from natural numbers
      (0 to 9) is also achieved based on the same system. This work not only opens up
      inspiring horizons for the design of novel electrochemical functional devices and
      complicated logic circuits, but also lays a solid foundation for potential logic
      programmed target detection.

PMID- 30210771
TI  - Bifunctional iminophosphorane catalysed enantioselective sulfa-Michael addition
      of alkyl thiols to alkenyl benzimidazoles.
AB  - The first enantioselective sulfa-Michael addition of alkyl thiols to alkenyl
      benzimidazoles, enabled by a bifunctional iminophosphorane (BIMP) organocatalyst,
      is described. The iminophosphorane moiety of the catalyst provides the required
      basicity to deprotonate the thiol nucleophile while the chiral scaffold and H
      bond donor control facial selectivity. The reaction is broad in scope with
      respect to the thiol and benzimidazole reaction partners with the reaction
      proceeding in up to 98% yield and 96 : 4 er.

PMID- 30210774
TI  - Electric-field induced bistability in single-molecule conductance measurements
      for boron coordinated curcuminoid compounds.
AB  - We have studied the single-molecule conductance of a family of curcuminoid
      molecules (CCMs) using the mechanically controlled break junction (MCBJ)
      technique. The CCMs under study contain methylthio (MeS-) as anchoring groups:
      MeS-CCM (1), the free-ligand organic molecule, and two coordination compounds,
      MeS-CCM-BF2 (2) and MeS-CCM-Cu (3), where ligand 1 coordinates to a boron center
      (BF2 group) and to a CuII moiety, respectively. We found that the three molecules
      present stable molecular junctions allowing detailed statistical analysis of
      their electronic properties. Compound 3 shows a slight increase in the
      conductance with respect to free ligand 1, whereas incorporation of BF2 (compound
      2) promotes the presence of two conductance states in the measurements.
      Additional experiments with control molecules point out that this bistability is
      related to the combination of MeS- anchoring groups and the BF2 moiety within the
      structure of the molecules. Theoretical calculations show that this can be
      explained by the presence of two conformers once compound 2 is anchored between
      the gold electrodes. An energy minimum is found for a flat structure but there is
      a dramatic change in the magnitude and orientation of dipole moment (favouring a
      non-flat conformer in the presence of an external electric field) due to a
      conformational change of one of the terminal MeS- groups. The results thus point
      to an intricate interplay between the applied bias voltage and the molecule
      dipole moment which could be the basis for designing new molecules aiming at
      controlling their conformation in devices.

PMID- 30210775
TI  - Probing key elements of teixobactin-lipid II interactions in membranes.
AB  - Teixobactin (Txb) is a recently discovered antibiotic against Gram-positive
      bacteria that induces no detectable resistance. The bactericidal mechanism is
      believed to be the inhibition of cell wall biosynthesis by Txb binding to lipid
      II and lipid III. Txb binding specificity likely arises from targeting of the
      shared lipid component, the pyrophosphate moiety. Despite synthesis and
      functional assessment of numerous chemical analogs of Txb, and consequent
      identification of the Txb pharmacophore, the detailed structural information of
      Txb-substrate binding is still lacking. Here, we use molecular modeling and
      microsecond-scale molecular dynamics simulations to capture the formation of Txb
      lipid II complexes at a membrane surface. Two dominant binding conformations were
      observed, both showing characteristic lipid II phosphate binding by the Txb
      backbone amides near the C-terminal cyclodepsipeptide (d-Thr8-Ile11) ring.
      Additionally, binding by Txb also involved the side chain hydroxyl group of Ser7,
      as well as a secondary phosphate binding provided by the side chain of l-allo
      enduracididine. Interestingly, those conformations differ by swapping two groups
      of hydrogen bond donors that coordinate the two phosphate moieties of lipid II,
      resulting in opposite orientations of lipid II binding. In addition, residues d
      allo-Ile5 and Ile6 serve as the membrane anchors in both Txb conformations,
      regardless of the detailed phosphate binding interactions near the
      cyclodepsipeptide ring. The role of hydrophobic residues in Txb activity is
      primarily for its membrane insertion, and subsidiarily to provide non-polar
      interactions with the lipid II tail. Based on the Txb-lipid II interactions
      captured in their complexes, as well as their partitioning depths into the
      membrane, we propose that the bactericidal mechanism of Txb is to arrest cell
      wall synthesis by selectively inhibiting the transglycosylation of peptidoglycan,
      while possibly leaving the transpeptidation step unaffected. The observed
      "pyrophosphate caging" mechanism of lipid II inhibition appears to be similar to
      some lantibiotics, but different from that of vancomycin or bacitracin.

PMID- 30210776
TI  - Microwave-assisted CVD-like synthesis of dispersed monolayer/few-layer N-doped
      graphene encapsulated metal nanocrystals for efficient electrocatalytic oxygen
      evolution.
AB  - Herein a novel and general microwave-assisted chemical vapor deposition (CVD)
      like synthetic strategy was developed to realize the ultrafast synthesis of a
      series of well-dispersed monolayer/few-layer N-doped graphene shell encapsulated
      metal nanocrystals (M@NC) by using a metal-organic framework (MOF) on graphene as
      precursors for the first time. Unlike traditional programmed heat treatment, this
      microwave-assisted method decomposed the MOF into separated metal and carbon- and
      nitrogen-containing gases rather than aggregated metal and carbon composites
      during the initial thermal transformation stages. This change ensured the
      effective control of the subsequent formation process of carbon on the surface of
      metal and led to the formation of well-dispersed M@NC with monolayer/few-layer
      NC. Moreover, the graphene substrate promoted the full exposure of all active
      monolayer/few-layer NC, and thus the obtained FeNi@NC/graphene displays the best
      electrocatalytic properties for the oxygen evolution reaction of all of the
      previously reported M@NC based catalysts, including the lowest overpotential (261
      mV) at 10 mA cm-2 in alkaline electrolyte (1 M KOH), the smallest Tafel slope (40
      mV dec-1) and excellent durability for at least 120 h.

PMID- 30210777
TI  - The Power of Shape: How Shape of Node-Link Diagrams Impacts Aesthetic
      Appreciation and Triggers Interest.
AB  - Positive effects of aesthetically appreciated designs have long been studied and
      confirmed since the 19th century: such designs are more enjoyable, they are more
      forgivable for glitches and can increase users' performance. In the field of
      information visualization, studies of aesthetics are still a niche approach. In
      the current study, we aim to specifically understand which parameters in a
      visualization of node-link diagrams make them aesthetically pleasing-an important
      extension to already existing research on usability and readability aspects. We
      investigated how the shape of the outline of such diagrams influences the
      aesthetic judgments on two of the most important dimensions of aesthetic appeal:
      beauty and interest. We employed different outlines to node-link diagrams and
      compared them with uniformly filled shapes, varying two important variables
      typically impacting aesthetics: complexity and curvature. This was done for a
      short (100 ms) and ad libitum presentation time. Diagrams with curvier outlines
      were perceived as more beautiful, while diagrams with more complex outlines were
      considered to be more interesting. These dependencies already exist for
      presaccadic perception (100 ms) and are slightly stronger for unlimited
      presentation time. We also found that curvature is a predictor for beauty only
      for unlimited presentation time. Aesthetic appeal was very similar for diagrams
      and pure shapes, so many results from fundamental research on aesthetics can
      potentially be transferred to the community of network visualization, assisting
      to improve visualizations also in aesthetic regards.

PMID- 30210779
TI  - Influence of ZnO thin film crystallinity on in vitro biocompatibility.
AB  - This study evaluated the cytocompatibility of single- and poly-crystalline ZnO
      thin films using extract and direct contact methods. Exposure to poly-crystalline
      ZnO extract resulted in reduced cell viability, on average 82%/70% as measured by
      MTS/LDH assays, respectively. Direct exposure to both single- and poly
      crystalline ZnO thin films resulted in reduced cell viability, which was
      attributed to anoikis due to inhibition of cell adhesion to the substrate by
      zinc. Intracellular zinc imaging suggests that single crystalline ZnO thin films
      do not result in a significant change in intracellular zinc concentrations.
      Overall, the results suggest that single-crystalline ZnO thin films have better
      short-term (24 h) cytocompatibility and support their potential to serve as a
      biocompatible sensor material.

PMID- 30210778
TI  - TARC: Turkish aripiprazole consensus report- Aripiprazole use and switching from
      other antipsychotics to aripiprazole- consensus recommendations by a Turkish
      multidisciplinary panel.
AB  - In this review, we have attempted to share our 10 years' clinical experience with
      aripiprazole use and switching from other antipsychotics to aripiprazole. There
      are various reasons for switching, including a partial or complete lack of
      efficacy, adverse side effects, and partial or noncompliance with medication.
      Aripiprazole has some unique receptor-binding qualities that provides some
      advantages over other antipsychotics in certain clinical situations. We have
      covered potential clinical scenarios for aripiprazole use as a single agent and
      switching from other agents in inpatient and outpatient settings. Patients
      switched from other antipsychotics to aripiprazole have been shown to benefit
      from significant improvements in clinical response and tolerability. This review
      examines the strategies for switching patients from antipsychotic drugs to
      aripiprazole.

PMID- 30210780
TI  - The 2018 Bioinformatics Open Source Conference (GCCBOSC 2018).
AB  - In 2018, the annual Bioinformatics Open Source Conference was held for the first
      time in conjunction with the Galaxy Community Conference, as an experiment to see
      if we could reach people in the bioinformatics community who aren't part of the
      audience attracted by ISMB. Held in June 2018 at Reed College in Portland,
      Oregon, GCCBOSC (Galaxy Community Conference and Bioinformatics Open Source
      Conference) attracted over 300 participants from around the world. The meeting
      started with two days of training, followed by two days of talks and poster/demo
      sessions (with some joint and some parallel sessions). The joint sessions
      included well-received keynote talks by Tracy Teal, Fernando Perez and Lucia
      Peixoto, as well as a panel discussion about documentation and training. After
      the main meeting, many attendees stayed for up to four additional collaboration
      days, an extended version of the Codefests that have been held in conjunction
      with previous BOSCs. GCCBOSC was a successful experiment. The organizers
      concluded that the best way to serve the broadest community of potential BOSC
      attendees will be to partner some years with the International Society for
      Computational Biology (ISMB) and others with GCC.

PMID- 30210781
TI  - Recent advances in understanding and treating acute respiratory distress
      syndrome.
AB  - Acute respiratory distress syndrome (ARDS) is a clinically and biologically
      heterogeneous disorder associated with many disease processes that injure the
      lung, culminating in increased non-hydrostatic extravascular lung water, reduced
      compliance, and severe hypoxemia. Despite enhanced understanding of molecular
      mechanisms, advances in ventilatory strategies, and general care of the
      critically ill patient, mortality remains unacceptably high. The Berlin
      definition of ARDS has now replaced the American-European Consensus Conference
      definition. The recently concluded Large Observational Study to Understand the
      Global Impact of Severe Acute Respiratory Failure (LUNG-SAFE) provided worldwide
      epidemiological data of ARDS including prevalence, geographic variability,
      mortality, and patterns of mechanical ventilation use. Failure of clinical
      therapeutic trials prompted the investigation and subsequent discovery of two
      distinct phenotypes of ARDS (hyper-inflammatory and hypo-inflammatory) that have
      different biomarker profiles and clinical courses and respond differently to the
      random application of positive end expiratory pressure (PEEP) and fluid
      management strategies. Low tidal volume ventilation remains the predominant
      mainstay of the ventilatory strategy in ARDS. High-frequency oscillatory
      ventilation, application of recruitment maneuvers, higher PEEP, extracorporeal
      membrane oxygenation, and alternate modes of mechanical ventilation have failed
      to show benefit. Similarly, most pharmacological therapies including keratinocyte
      growth factor, beta-2 agonists, and aspirin did not improve outcomes. Prone
      positioning and early neuromuscular blockade have demonstrated mortality benefit,
      and clinical guidelines now recommend their use. Current ongoing trials include
      the use of mesenchymal stem cells, vitamin C, re-evaluation of neuromuscular
      blockade, and extracorporeal carbon dioxide removal. In this article, we describe
      advances in the diagnosis, epidemiology, and treatment of ARDS over the past
      decade.

PMID- 30210782
TI  - Recent advances in allergic rhinitis.
AB  - Allergic rhinitis affects 20 to 30% of adults in both the United States and
      Europe and perhaps a somewhat higher percentage of children. In addition to nasal
      and ocular symptoms directly related to the allergic process, interference of
      these symptoms with sleep leads to daytime sleepiness and impaired quality of
      life. Patients miss work because of symptoms but an even greater problem is
      interference with work productivity, or presenteeism, which has been reported to
      be the biggest contributor to the total economic cost of allergic rhinitis. There
      has been increasing awareness that many patients with either seasonal or
      perennial symptoms but negative skin and in vitro tests for allergen sensitivity
      have local nasal allergy, diagnosable by the presence of allergen-specific IgE in
      their nasal secretions or a positive nasal allergen challenge or both. The
      pharmaceutical management of allergic rhinitis rests on symptomatic treatment
      with antihistamines that perhaps are more effectively administered intranasally
      than orally and intranasal corticosteroids. Allergen immunotherapy is very
      effective, even for local allergic rhinitis, and the shortcomings of subcutaneous
      immunotherapy of inconvenience and safety are reduced by the introduction of
      sublingual immunotherapy (SLIT). Use of the latter is currently somewhat limited
      by the lack of appropriate dosing information for SLIT liquids and the limited
      number of allergens for which SLIT tablets are available.

PMID- 30210783
TI  - Recent advances in diffusion neuroimaging: applications in the developing preterm
      brain.
AB  - Measures obtained from diffusion-weighted imaging provide objective indices of
      white matter development and injury in the developing preterm brain. To date,
      diffusion tensor imaging (DTI) has been used widely, highlighting differences in
      fractional anisotropy (FA) and mean diffusivity (MD) between preterm infants at
      term and healthy term controls; altered white matter development associated with
      a number of perinatal risk factors; and correlations between FA values in the
      white matter in the neonatal period and subsequent neurodevelopmental outcome.
      Recent developments, including neurite orientation dispersion and density imaging
      (NODDI) and fixel-based analysis (FBA), enable white matter microstructure to be
      assessed in detail. Constrained spherical deconvolution (CSD) enables multiple
      fibre populations in an imaging voxel to be resolved and allows delineation of
      fibres that traverse regions of fibre-crossings, such as the arcuate fasciculus
      and cerebellar-cortical pathways. This review summarises DTI findings in the
      preterm brain and discusses initial findings in this population using CSD, NODDI,
      and FBA.

PMID- 30210784
TI  - Insulin resistance indices and coronary risk in adults from Maracaibo city,
      Venezuela: A cross sectional study.
AB  - Background: Insulin resistance (IR) is a metabolic disorder related to
      atherosclerosis. Its measurement is of great importance not only as a marker of
      diabetes but also for cardiovascular disease. The aim of this research study was
      to evaluate the relationship between various IR indices and coronary risk in an
      adult population from Maracaibo city, Venezuela. Methods: The Maracaibo City
      Metabolic Syndrome Prevalence Study is a descriptive, cross-sectional study with
      random and multi-stage sampling. In this sub study, 1272 individuals of both
      genders were selected with the measurement of basal insulin and coronary risk
      according to the Framingham-Wilson formula calibrated for our population. The
      insulin resistance indices evaluated were HOMA2-IR, triglycerides and glucose
      index (TyG) and triglycerides/HDL ratio (TG/HDL). The predictive capacity and
      association between each index and the coronary risk event in 10 years were
      determined. Results: Of the evaluated population, 55.2% were female, 34.8% had a
      coronary risk >=5% in 10 years, with the TG/HDL and TyG indices showing the
      highest AUC 0.712 (0.681-0.743) and 0.707 (0.675-0.739), respectively; compared
      to HOMA2-IR. Both were also the indices most associated with increased coronary
      risk, especially TG/HDL >=3 with a higher association [OR = 2.83 (1.74-4.61);
      p<0.01] after multivariable adjustment. Conclusions: TyG (>=4.5) and TG/HDL (>=3)
      indices showed a great predictive capacity of higher coronary risk, with being
      TG/HDL more associated even after adjusting for abdominal obesity and hs-CRP.
      Therefore, these represent useful tools for determining IR.

PMID- 30210786
TI  - Lost in translation.
AB  - Translation in cognitive neuroscience remains beyond the horizon, brought no
      closer by supposed major advances in our understanding of the brain. Unless our
      explanatory models descend to the individual level-a cardinal requirement for any
      intervention-their real-world applications will always be limited. Drawing on an
      analysis of the informational properties of the brain, here we argue that
      adequate individualisation needs models of far greater dimensionality than has
      been usual in the field. This necessity arises from the widely distributed
      causality of neural systems, a consequence of the fundamentally adaptive nature
      of their developmental and physiological mechanisms. We discuss how recent
      advances in high-performance computing, combined with collections of large-scale
      data, enable the high-dimensional modelling we argue is critical to successful
      translation, and urge its adoption if the ultimate goal of impact on the lives of
      patients is to be achieved.

PMID- 30210787
TI  - Reproductive performance of asian catfish ( Hemibagrus wyckii Bagridae), a
      candidate species for aquaculture.
AB  - Background:Hemibagrus wyckii Bagridae is one of the most important economic fish
      species that lives in the rivers and reservoir in Riau Province, Indonesia. The
      present study aimed to determine the reproductive performance of H.wyckii under
      culture conditions. Methods: A total of 10 female and 10 male fish were selected,
      and weight, length, characteristics of egg and sperm, and hatchery performance
      were measured. Eggs were fertilized using the dry method. Egg weight and egg
      diameters were measured for 50 eggs per female. Egg size (50 eggs for each fish)
      was measured using an Olympus microscope (CX40). Then, saline solution was added
      over the eggs, followed by the addition of pooled sperm from 10 males. Results:
      Average relative fecundity, egg weight and egg diameter were 2060+/-512 eggs/kg
      fish, 29.86+/-1.21 mg and 2.67+/-0.26 mm, respectively. The fertilization rate
      and hatching rate were 60.91+/-4.68% and 42.91+/-2.92% respectively. Sperm
      characteristics such as volume per fish (mL), pH, concentration (per mL),
      motility (%) and duration of motility (second) were 0.82+/-0.20, 7.15+/-0.12,
      3.68+/-0.15, 72.77+/-1.46 and 47.5+/-4.84, respectively. Conclusion: The study
      results and scientific observations regarding reproductive performance suggest
      that H. wyckii can be considered a new candidate species for aquaculture.

PMID- 30210788
TI  - Preliminary study on the inhibitory effect of seaweed Gracilaria verrucosa
      extract on biofilm formation of Candida albicans cultured from the saliva of a
      smoker.
AB  - Background:Candida albicans is an opportunistic fungus that infects the oral
      cavity. Increases in colony numbers of C. albicans can be caused by multiple
      factors, such as smoking, a weakened immune system, taking antibiotics and with
      immune-compromised individuals. Smoking can increase the virulence factor of C.
      albicans and make it stronger. One of the virulence factors of C. albicans is the
      biofilm it forms. The C. albicans biofilm makes it more tolerant to extracts of
      the seaweed Gracilariaverrucosa, which has antifungal activity. The objective of
      the study was to examine the ability of the G.verrucosa extracts to inhibit the
      formation of biofilm by C. albicans obtained from the saliva of smoker. Methods:
      A total of six concentrations of G. verrucosa (6.25, 12.5, 25, 50, 75 and 100%)
      were tested in this study. The positive control was fluconazole 0.31 ug/ml C.
      albicans was taken from the saliva of one smoker in Faculty of Dentistry, Syiah
      Kuala University. The total amount of biofilm was assessed using an ELISA reader.
      The data were subjected to Kruskal-Wallis test at a significance limit of p<0.05.
      Results: The seaweed extract has three bio-active compounds: steroids, terpenoid,
      and tannins. The results showed that the inhibitory activity of seaweed on C.
      albicans biofilm formation increases as its concentration increases. The highest
      effectiveness was recorded at a seaweed concentration of 100% at 48 h of
      exposure. Conclusions: The optimal inhibition of the C. albicans biofilm
      formation was recorded at the concentration of 100% G. verrucosa after 48 hours
      of exposure.

PMID- 30210789
TI  - Acute hip fracture surgery anaesthetic technique and 30-day mortality in Sweden
      2016 and 2017: A retrospective register study.
AB  - Background: Hip fractures yearly affect 1.6 million patients worldwide, often the
      elderly with complex comorbidity. Mortality following surgery for acute hip
      fracture is high. The high mortality rate is multifactorial; high age,
      comorbidities and complication/deterioration in health following surgery. Whether
      the anaesthesia technique affects the 30-day mortality rate has been studied
      widely without reaching a consensus. The primary aim of this study was to
      determine anaesthetic techniques used in Sweden and their impact on the 30-day
      mortality rate in the elderly, who underwent acute hip fracture surgery. Other
      aims were to study the impact of age, gender, ASA class, fracture type and delay
      in surgery on the 30-day mortality rate. Methods: Data from 13,649 patients >=50
      years old who had undergone acute hip fracture surgery and been reported to
      Swedish perioperative register (SPOR) between 2016 and 2017 were analysed.    
      Results: The most commonly used anaesthetic technique was neuraxial anaesthesia
      (NA; 11257, 82%), followed by general anaesthesia (GA; 2190, 16%) and combined
      general and neuraxial anaesthesia (CA; 202, 1.5%) out of the 13,649 studied. The
      30-day mortality rate was 7.7% for the entire cohort; GA 7.8%, NA 7.7% and CA
      7.4%. Mortality was higher in elderly patients, those with a high ASA class,
      pertrochanteric fracture and males.     Conclusions: The present study showed
      that NA is by far the most common anaesthetic technique for acute hip fracture
      surgery in Sweden. However, the anaesthetic technique used during this type of
      surgery had no impact on the 30-day mortality rate of patients. Increasing age,
      ASA class and male gender increased the 30-day mortality.

PMID- 30210785
TI  - Factors influencing the higher incidence of tuberculosis among migrants and
      ethnic minorities in the UK.
AB  - Migrants and ethnic minorities in the UK have higher rates of tuberculosis (TB)
      compared with the general population. Historically, much of the disparity in
      incidence between UK-born and migrant populations has been attributed to
      differential pathogen exposure, due to migration from high-incidence regions and
      the transnational connections maintained with TB endemic countries of birth or
      ethnic origin. However, focusing solely on exposure fails to address the
      relatively high rates of progression to active disease observed in some
      populations of latently infected individuals. A range of factors that
      disproportionately affect migrants and ethnic minorities, including genetic
      susceptibility, vitamin D deficiency and co-morbidities such as diabetes mellitus
      and HIV, also increase vulnerability to infection with Mycobacterium tuberculosis
      (M.tb) or reactivation of latent infection. Furthermore, ethnic socio-economic
      disparities and the experience of migration itself may contribute to differences
      in TB incidence, as well as cultural and structural barriers to accessing
      healthcare. In this review, we discuss both biological and anthropological
      influences relating to risk of pathogen exposure, vulnerability to infection or
      development of active disease, and access to treatment for migrant and ethnic
      minorities in the UK.

PMID- 30210790
TI  - Identifying communities from multiplex biological networks by randomized
      optimization of modularity.
AB  - The identification of communities, or modules, is a common operation in the
      analysis of large biological networks. The Disease Module Identification DREAM
      challenge established a framework to evaluate clustering approaches in a
      biomedical context, by testing the association of communities with GWAS-derived
      common trait and disease genes. We implemented here several extensions of the
      MolTi software that detects communities by optimizing multiplex (and monoplex)
      network modularity. In particular, MolTi now runs a randomized version of the
      Louvain algorithm, can consider edge and layer weights, and performs recursive
      clustering. On simulated networks, the randomization procedure clearly improves
      the detection of communities. On the DREAM challenge benchmark, the results
      strongly depend on the selected GWAS dataset and enrichment p -value threshold.
      However, the randomization procedure, as well as the consideration of weighted
      edges and layers generally increases the number of trait and disease community
      detected. The new version of MolTi and the scripts used for the DMI DREAM
      challenge are available at: https://github.com/gilles-didier/MolTi-DREAM.

PMID- 30210791
TI  - drawProteins: a Bioconductor/R package for reproducible and programmatic
      generation of protein schematics.
AB  - Protein schematics are valuable for research, teaching and knowledge
      communication. However, the tools used to automate the process are challenging.
      The purpose of the drawProteins package is to enable the generation of schematics
      of proteins in an automated fashion that can integrate with the Bioconductor/R
      suite of tools for bioinformatics and statistical analysis. Using UniProt
      accession numbers, the package uses the UniProt API to get the features of the
      protein from the UniProt database. The features are assembled into a data frame
      and visualized using adaptations of the ggplot2 package. Visualizations can be
      customised in many ways including adding additional protein features information
      from other data frames, altering colors and protein names and adding extra layers
      using other ggplot2 functions. This can be completed within a script that makes
      the workflow reproducible and sharable.

PMID- 30210794
TI  - Jejunal lymphangioma causing intussusception in an adult: An unusual case with
      review of the literature.
AB  - Introduction: Adult intussusception is rare, and 90% are due to a lead point
      secondary to a pathologic condition. Lymphangioma is an uncommon tumor of the
      lymphatic system and is rarely found within the small bowel. Small bowel
      lymphangioma causing intussuception in an adult is a rare occurrence, with three
      very distinct rare pathologies occurring simultaneously. Case description: A 70
      year-old male patient with multiple pre-existing pathologies such as advanced
      ADPKD, multiple persistent tubulovillous colon polyps and colon cancer in situ,
      was hospitalized due to rapid weight loss of 20 lbs, hematemesis, and abdominal
      pain. He was subsequently found to have jejunal intussusception caused by two
      lymphangiomas of the small bowel. The portion of intussuscepted jejunum was
      resected and final diagnosis on pathology was two jejunal lymphangiomas.
      Discussion: Lymphangiomas of the small bowel are rare, but increasing in
      incidence due to the accessibility of endoscopic evaluations. A hypothetical
      connection between lymphangioma and ADPKD is unknown, but both diseases are built
      on a foundation of cystogenesis. There is little known about the effect ADPKD on
      cystogenesis and tumor formation extra-renally, and there is a possible
      correlation between genetic mutations in polycystin and cystic tumors such as
      lymphangiomas. Conclusion: Lymphangioma, although rare in the small bowel, is a
      possible cause of intussusception and should be considered on the differential of
      abdominal pain in adults. The pathogenesis of polycystic kidney disease has
      implications that could predispose to cystic development beyond the kidney, and
      more research into the genetic mechanism behind the disease is necessary to
      support or deny this claim.

PMID- 30210792
TI  - Tourette syndrome research highlights from 2017.
AB  - This is the fourth yearly article in the Tourette Syndrome Research Highlights
      series, summarizing research from 2017 relevant to Tourette syndrome and other
      tic disorders. The authors briefly summarize reports they consider most important
      or interesting. The  highlights from 2018 article is being drafted on the
      Authorea online authoring platform, and readers are encouraged to add references
      or give feedback on our selections using the comments feature on that page. After
      the calendar year ends, the article is submitted as the annual update for the
      Tics collection on F1000Research.

PMID- 30210795
TI  - The effect of far infrared radiation therapy on inflammation regulation in
      lipopolysaccharide-induced peritonitis in mice.
AB  - Objective: Far infrared radiation has been widely used in a variety of healthcare
      institutions and clinical research. Previous studies have shown that far infrared
      radiation can promote blood circulation and enhance the functioning of the immune
      system. Many patients receiving peritoneal dialysis have been co-treated with far
      infrared radiation to reduce the occurrence of inflammation. This study seeks to
      evaluate the effects of far infrared radiation therapy on inflammation. Method:
      We used the lipopolysaccharide-induced peritonitis mouse model to study the
      effect of far infrared radiation treatment. Sixteen mice were randomly divided
      into two groups, a far infrared radiation treatment group (n = 8) and a non-far
      infrared radiation treatment group (n = 8). Collected blood samples were studied
      by analyzing the RNA level of peripheral blood mononuclear cells and the plasma
      protein levels of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha),
      and endothelial nitric oxide synthase (eNOS). Results: The administration of far
      infrared radiation inhibited the RNA levels of interleukin-6 and TNF-alpha after
      stimulation by lipopolysaccharide. The far infrared radiation treatment inhibited
      the endothelial nitric oxide synthase RNA levels at 1 h, but the RNA levels
      returned close to the baseline level after 2 h. In the control group, the
      endothelial nitric oxide synthase RNA levels were continuously decreasing. The
      interleukin-6 concentration in the plasma of the far infrared radiation group
      showed significant inhibition 30 min after lipopolysaccharide stimulation. The
      tumor necrosis factor alpha RNA concentration in plasma of the far infrared
      radiation group was significantly reduced 2 h after lipopolysaccharide
      stimulation. Conclusion: Far infrared radiation therapy can inhibit interleukin-6
      and tumor necrosis factor alpha RNA levels of peripheral blood mononuclear cells
      and recover endothelial nitric oxide synthase expression. These results
      demonstrate that far infrared radiation therapy might aid in reducing the level
      of inflammation experienced by patients going through peritoneal dialysis
      treatment.

PMID- 30210796
TI  - Bridging the gap: A user-driven study on new ways to support self-care and
      empowerment for patients with hip fracture.
AB  - Objectives: In future healthcare systems, individuals are expected to be more
      involved in managing their health and preventing illness. A previous study of
      patient empowerment on a hip fracture pathway uncovered a gap between what the
      healthcare system provided and patients' needs and wishes. The aim of this study
      was to investigate whether a user-driven approach and a participatory design
      could provide a solution that would bridge this gap. Methods: Four workshops and
      a laboratory test were conducted with healthcare professionals to co-create a
      final prototype. This was performed in iterative processes through continuous
      interviews and face-to-face evaluation with patients, together with field studies
      in patients' homes, to maintain relevance to end-users, that is, patients and
      healthcare professionals. The data were analysed according to the plan, act,
      observe and reflect methodology of iterative processes in participatory design.
      Results: Our results contribute to a key research area within patient
      involvement. By using participatory design, patients and healthcare professionals
      gained a mutual understanding and collaborated to create a technological solution
      that would encompass needs and wishes. Patient empowerment also involved giving
      healthcare professionals a means of empowerment, by providing them with a
      platform to support patient education. We found that one solution to bridging the
      aforementioned gap could be an app, including a range of educational features
      that would accommodate different learning styles. Conclusion: In developing a
      technological solution, user involvement in a participatory design ensures
      usability and inclusion of the requested functionalities. This can help bridge
      the gap between what the healthcare system provided and patients' needs and
      wishes and support patients' individual empowerment needs and self-care capacity.
      Together with the tools and techniques, the setting in which PD unfolds should be
      thoughtfully planned.

PMID- 30210797
TI  - Kaposi's sarcoma in an HIV-negative chronic lymphocytic leukemia patient without
      immunosuppressive therapy: A case report.
AB  - Kaposi's sarcoma is a neoplasm of endothelial cells. That vascular tumor is
      usually limited to the skin, but it may involve mucous membranes, visceral
      organs, and lymph nodes. Serological evidence has shown that human herpesvirus 8
      infection is required for the development of Kaposi's sarcoma. Chronic
      lymphocytic leukemia is the most common leukemia all over the world. Increased
      skin cancer risk has been reported for patients with chronic lymphocytic
      leukemia. The relation between these two pathologies has not yet been clarified.
      We report a case of Kaposi's sarcoma along with chronic lymphocytic leukemia in a
      patient who did not receive therapy for chronic lymphocytic leukemia.

PMID- 30210793
TI  - Fluorescence-based tools to probe G-quadruplexes in cell-free and cellular
      environments.
AB  - Biophysical and biochemical investigations provide compelling evidence connecting
      the four-stranded G-quadruplex (GQ) structure with its role in regulating
      multiple cellular processes. Hence, modulating the function of GQs by using small
      molecule binders is being actively pursued as a strategy to develop new
      chemotherapeutic agents. However, sequence diversity and structural polymorphism
      of GQs have posed immense challenges in terms of understanding what conformation
      a G-rich sequence adopts inside the cell and how to specifically target a GQ
      motif amidst several other GQ-forming sequences. In this context, here we review
      recent developments in the applications of biophysical tools that use
      fluorescence readout to probe the GQ structure and recognition in cell-free and
      cellular environments. First, we provide a detailed discussion on the utility of
      covalently labeled environment-sensitive fluorescent nucleoside analogs in
      assessing the subtle difference in GQ structures and their ligand binding
      abilities. Furthermore, a detailed discussion on structure-specific antibodies
      and small molecule probes used to visualize and confirm the existence of DNA and
      RNA GQs in cells is provided. We also highlight the open challenges in the study
      of tetraplexes (GQ and i-motif structures) and how addressing these challenges by
      developing new tools and techniques will have a profound impact on tetraplex
      directed therapeutic strategies.

PMID- 30210798
TI  - Acute presentation of Sinding-Larsen-Johansson disease simulating patella sleeve
      fracture: A case report.
AB  - Objectives: Diagnosis of Sinding-Larsen-Johansson disease may not be an easy
      task. Several sport-related conditions affect the distal pole of the patella in
      the adolescent, and treatment varies considerably. The article describes a
      patient that had radiographic features of Sinding-Larsen-Johansson disease
      associated with an atypical acute presentation. Methods: Case report and
      literature review. Results: A 10-year-old boy presented with a sudden pain after
      a noncontact soccer injury. He had tenderness and swelling over the patella.
      Radiographs showed minimally displaced distal patellar ossicle. Magnetic
      resonance imaging excluded sleeve cartilaginous injury and documented Sinding
      Larsen-Johansson disease. The knee was immobilized briefly. There was complete
      healing of the injury in 4-week follow-up radiographs. Conclusion: Emergency
      physicians, radiologists, and orthopedic surgeons should be aware of the acute
      presentation of Sinding-Larsen-Johansson disease after knee injuries.

PMID- 30210799
TI  - Distal embolization of coronary calcified nodule after rotational atherectomy.
AB  - A 62-year-old man with effort angina underwent percutaneous coronary intervention
      in our hospital. The target lesion was severely calcified at the mid part of the
      right coronary artery. Pre-procedural intravascular imaging and optical frequency
      domain imaging showed a calcified nodule at the lesion. We performed rotational
      atherectomy with a 2.0 mm burr and observed an increase in the lumen area;
      however, a large amount of calcified nodule persisted. We decided to perform
      rotational atherectomy with a burr size of 2.25 mm; however, distal embolization
      of the calcified nodule occurred. We failed to retrieve the embolus; hence, we
      performed balloon dilatation with a 2.0-mm balloon, which was successfully
      performed. Yet, the lesion with the embolus immediately recoiled. Finally, a drug
      eluting stent was implanted in both the distal lesion with the embolus and the
      lesion with the calcified nodule. Final coronary angiography showed good results.
      We confirmed good stent expansion and that calcified nodule was compressed
      outside the stent. Atherectomy of a calcified nodule is effective at achieving
      sufficient stent expansion and reducing the risk of vessel perforation. However,
      we experienced distal embolization of the calcified nodule at the time of
      rotational atherectomy and so distal embolization should be considered at the
      time of treatment of calcified nodule.

PMID- 30210800
TI  - The continual threat of influenza virus infections at the human-animal interface:
      What is new from a one health perspective?
AB  - This year, in 2018, we mark 100 years since the 1918 influenza pandemic. In the
      last 100 years, we have expanded our knowledge of public health and increased our
      ability to detect and prevent influenza; however, we still face challenges
      resulting from these continually evolving viruses. Today, it is clear that
      influenza viruses have multiple animal reservoirs (domestic and wild), making
      infection prevention in humans especially difficult to achieve. With this report,
      we summarize new knowledge regarding influenza A, B, C and D viruses and their
      control. We also introduce how a multi-disciplinary One Health approach is
      necessary to mitigate these threats.

PMID- 30210801
TI  - Mitochondrial DNA 3243A>T mutation in a patient with MELAS syndrome.
AB  - Approximately 80% of cases of mitochondrial myopathy, encephalopathy, lactic
      acidosis, and stroke-like episodes (MELAS) harbor a heteroplasmic m.3243A>G
      transition in the tRNALeu (UUR) (MTTL1) gene. We report a MELAS case with a rare
      heteroplasmic m.3243A>T mutation found by direct sequencing of MTTL1. This
      mutation has been previously reported in 5 cases, of which 2 cases had the MELAS
      phenotype. Our case also strengthens the hypothesis that the m.3243A>T mutation
      can cause the MELAS phenotype.

PMID- 30210802
TI  - Effectiveness of a Web-Based eHealth Portal for Delivery of Care to Home Dialysis
      Patients: A Single-Arm Pilot Study.
AB  - Background: Improving a patient's experience with their care through an online
      interface for communication (an eHealth patient portal) has been shown to be
      beneficial in some studies of chronic disease populations. However, little is
      known about the effectiveness of an eHealth portal for delivery of care to home
      dialysis patients. Objectives: Primary: To determine whether an eHealth portal is
      effective at improving a patient's experience with their home dialysis care.
      Secondary: (1) To determine whether an eHealth portal improves health-related
      quality of life for home dialysis patients, (2) to assess patient satisfaction
      with an eHealth portal and perceived impact on aspects of their home dialysis
      therapy and health, (3) to determine the acceptability of the eHealth portal
      software, and (4) to determine the change in telephone usage for communication
      after patient adoption of an eHealth portal. Design: Single-arm pilot trial with
      recruitment over a 4-month period. Setting: The multidisciplinary home dialysis
      clinic in Halifax Nova Scotia Canada. Patients: Adults (>18 years) receiving
      either home hemodialysis or peritoneal dialysis. Measurements: Consumer quality
      index (CQI), health-related quality of life using the EuroQol Five Dimensions
      Questionnaire (EQ-5D), acceptability of the eHealth portal software (using the
      Acceptability E-scale), and satisfaction/perceived impact (using a modified
      questionnaire). Methods: A web-based application (McKesson, Canada,
      RelayHealth(r)) allowed patients and health care workers to communicate through a
      secure, password-protected online portal that permitted visualization of the
      messaging history by patient and provider. Patients and the home dialysis health
      care team had the ability to send messages related to patient care at any time
      including proposed changes to medication, instructions after a clinic visit,
      times of new appointments, upcoming investigations, or questions about care.
      Patient experience with home dialysis care using the CQI, health-related quality
      of life using the EQ-5D, acceptability of the eHealth portal software, and
      satisfaction/perceived impact were assessed at baseline, 6, and 12 months of
      follow-up (where applicable). Total minutes of telephone communication was
      assessed prior to and after adoption of the portal. Results: Of the 41 patients
      who consented to join the portal, 27 (66%) created an online account. At
      baseline, patients had a positive experience for the care and communication
      provided by their nephrologist (CQI: 3.63, 95% confidence interval [CI]: 3.50
      3.76) and this did not change significantly over the study period. Similar
      results were observed for the care provided by other nephrology health care team
      members. Health-related quality of life using the EQ-5D score was 0.80
      (interquartile range [IQR]: 0.71-0.83) at baseline and this also did not
      significantly change over the study period. Patients were satisfied with the
      eHealth portal (mean Likert scale score of 6.5 +/- 0.6 in overall satisfaction,
      scale ranging from 1 completely dissatisfied to 10 completely satisfied), but
      only a minority (N = 12) completed a satisfaction questionnaire. Median monthly
      phone usage decreased from 12.5 to 10 minutes (P = .02) after adoption of the
      portal. Limitations: The study is limited by the small sample size, high rate of
      patient dropout, and limited response rate. Conclusions: In this study of home
      dialysis patients, we identified that an eHealth communication did not lead to
      significant improvements in patient experience with home dialysis care. Trial
      Registration: ClinicalTrials.gov number NCT02128347.

PMID- 30210804
TI  - 3D bacterial cellulose biofilms formed by foam templating.
AB  - Bacterial cellulose is a remarkable fibrous structural component of biofilms, as
      it forms a mechanically strong hydrogel with high water adsorption capabilities.
      Additionally, bacterial cellulose is biocompatible and therefore of potential
      interest for skin regeneration and wound healing applications. However, bacterial
      cellulose produced through conventional production processes at water-air
      interfaces lack macroporosity control, which is crucial for regenerative tissue
      applications. Here we demonstrate a straightforward and efficient approach to
      form a macroporous bacterial cellulose foam by foaming a mannitol-based media
      with a bacterial suspension of Gluconoacetobacter xylinus. The bacterial
      suspension foam is stabilized with Cremodan as a surfactant and viscosified with
      Xanthan preventing water drainage. Further foam stabilization occurs through
      cellulose formation across the foam network. As bacterial cellulose formation is
      influenced by the viscosity of the growth media, we fine-tuned the concentration
      of Xanthan to allow for bacterial cellulose formation while avoiding water
      drainage caused by gravity. With this simple approach, we were able to design 3D
      bacterial cellulose foams without any additional processing steps. We argue that
      this templating approach can further be used to design foamy biofilms for
      biotechnological approaches, increasing the surface area and therefore the yield
      by improving the exchange of nutrients and metabolic products.

PMID- 30210803
TI  - GePMI: A statistical model for personal intestinal microbiome identification.
AB  - Human gut microbiomes consist of a large number of microbial genomes, which vary
      by diet and health conditions and from individual to individual. In the present
      work, we asked whether such variation or similarity could be measured and, if so,
      whether the results could be used for personal microbiome identification (PMI).
      To address this question, we herein propose a method to estimate the significance
      of similarity among human gut metagenomic samples based on reference-free, long k
      mer features. Using these features, we find that pairwise similarities between
      the metagenomes of any two individuals obey a beta distribution and that a p
      value derived accordingly well characterizes whether two samples are from the
      same individual or not. We develop a computational framework called GePMI
      (Generating inter-individual similarity distribution for Personal Microbiome
      Identification) and apply it to several human gut metagenomic datasets (>300
      individuals and >600 samples in total). From the results of GePMI, most of the
      human gut microbiomes can be identified (auROC = 0.9470, auPRC = 0.8702). Even
      after antibiotic treatment or fecal microbiota transplantation, the individual k
      mer signature still maintains a certain specificity.

PMID- 30210806
TI  - The interaction of transcription factors controls the spatial layout of plant
      aerial stem cell niches.
AB  - The plant shoot apical meristem holds a stem cell niche from which all aerial
      organs originate. Using a computational approach we show that a mixture of
      monomers and heterodimers of the transcription factors WUSCHEL and HAIRY MERISTEM
      is sufficient to pattern the stem cell niche, and predict that immobile
      heterodimers form a regulatory "pocket" surrounding the stem cells. The model
      achieves to reproduce an array of perturbations, including mutants and tissue
      size modifications. We also show its ability to reproduce the recently observed
      dynamical shift of the stem cell niche during the development of an axillary
      meristem. The work integrates recent experimental results to answer the
      longstanding question of how the asymmetry of expression between the stem cell
      marker CLAVATA3 and its activator WUSCHEL is achieved, and recent findings of
      plasticity in the system.

PMID- 30210805
TI  - HCV-associated exosomes promote myeloid-derived suppressor cell expansion via
      inhibiting miR-124 to regulate T follicular cell differentiation and function.
AB  - Virus-infected cells can regulate non-permissive bystander cells, but the precise
      mechanisms remain incompletely understood. Here we report that this process can
      be mediated by transfer of viral RNA-loaded exosomes shed from infected cells to
      myeloid-derived suppressor cells (MDSCs), which in turn regulate the
      differentiation and function of T cells during viral infection. Specifically, we
      demonstrated that patients with chronic hepatitis C virus (HCV) infection
      exhibited significant increases in T follicular regulatory (TFR) cells and
      decreases in T follicular helper (TFH) cells. These MDSC-mediated T-cell
      dysregulations resulted in an increased ratio of TFR/TFH and IL-10 production in
      peripheral blood. Specifically, co-culture of MDSCs derived from HCV patients
      with healthy peripheral blood mononuclear cells (PBMCs) induced expansion of TFR,
      whereas depletion of MDSCs from PBMCs of HCV patients reduced the increases in
      TFR frequency and IL-10 production, and promoted the differentiation of IFN-gamma
      producing TFH cells. Importantly, we found that exosomes isolated from the plasma
      of HCV patients and supernatant of HCV-infected hepatocytes could drive monocytic
      myeloid cell differentiation into MDSCs. These exosomes were enriched in
      tetraspanins, such as CD63 and CD81, and contained HCV RNA, but exosomes isolated
      from patients with antiviral treatment contained no HCV RNA and could not induce
      MDSC differentiation. Notably, these HCV RNA-containing exosomes (HCV-Exo) were
      sufficient to induce MDSCs. Furthermore, incubation of healthy myeloid cells with
      these HCV-Exo inhibited the expression of miR-124, whereas reconstitution of
      PBMCs with miR-124 abolished the effects of HCV-Exo on MDSC induction. Taken
      together, these results indicate that HCV-associated exosomes can transfer
      immunomodulatory viral RNA from infected cells to neighboring immune cells and
      trigger MDSC expansion, which subsequently promotes TFR differentiation and
      inhibits TFH function. This study reveals a previously unrecognized path that
      represents a novel mechanism of immune dysregulation during chronic viral
      infection.

PMID- 30210807
TI  - HHV-6 encoded small non-coding RNAs define an intermediate and early stage in
      viral reactivation.
AB  - Human herpesvirus 6A and 6B frequently acquires latency. HHV-6 activation has
      been associated with various human diseases. Germ line inheritance of
      chromosomally integrated HHV-6 makes viral DNA-based analysis difficult for
      determination of early stages of viral activation. We characterized early stages
      of HHV-6 activation using high throughput transcriptomics studies and applied the
      results to understand virus activation under clinical conditions. Using a latent
      HHV-6A cell culture model in U2OS cells, we identified an early stage of viral
      reactivation, which we define as transactivation that is marked by transcription
      of several viral small non-coding RNAs (sncRNAs) in the absence of detectable
      increase in viral replication and proteome. Using deep sequencing approaches, we
      detected previously known as well as a new viral sncRNAs that characterized viral
      transactivation and differentiated it from latency. Here we show changes in human
      transcriptome upon viral transactivation that reflect multiple alterations in
      mitochondria-associated pathways, which was supported by observation of increased
      mitochondrial fragmentation in virus reactivated cells. Furthermore, we present
      here a unique clinical case of DIHS/DRESS associated death where HHV-6 sncRNA-U14
      was abundantly detected throughout the body of the patient in the presence of low
      viral DNA. In this study, we have identified a unique and early stage of viral
      activation that is characterized by abundant transcription of viral sncRNAs,
      which can serve as an ideal biomarker under clinical conditions.

PMID- 30210808
TI  - User considerations in assessing pharmacogenomic tests and their clinical support
      tools.
AB  - Pharmacogenomic (PGx) testing is gaining recognition from physicians, pharmacists
      and patients as a tool for evidence-based medication management. However,
      seemingly similar PGx testing panels (and PGx-based decision support tools) can
      diverge in their technological specifications, as well as the genetic factors
      that determine test specificity and sensitivity, and hence offer different values
      for users. Reluctance to embrace PGx testing is often the result of unfamiliarity
      with PGx technology, a lack of knowledge about the availability of curated
      guidelines/evidence for drug dosing recommendations, and an absence of wide
      spread institutional implementation efforts and educational support. Demystifying
      an often confusing and variable PGx marketplace can lead to greater acceptance of
      PGx as a standard-of-care practice that improves drug outcomes and provides a
      lifetime value for patients. Here, we highlight the key underlying factors of a
      PGx test that should be considered, and discuss the current progress of PGx
      implementation.

PMID- 30210809
TI  - Interrupted reprogramming of alveolar type II cells induces progenitor-like cells
      that ameliorate pulmonary fibrosis.
AB  - We describe here an interrupted reprogramming strategy to generate "induced
      progenitor-like (iPL) cells" from alveolar epithelial type II (AEC-II) cells. A
      carefully defined period of transient expression of reprogramming factors (Oct4,
      Sox2, Klf4, and c-Myc (OSKM)) is able to rescue the limited in vitro clonogenic
      capacity of AEC-II cells, potentially by activation of a bipotential progenitor
      like state. Importantly, our results demonstrate that interrupted reprogramming
      results in controlled expansion of cell numbers yet preservation of the
      differentiation pathway to the alveolar epithelial lineage. When transplanted to
      the injured lungs, AEC-II-iPL cells are retained in the lung and ameliorate
      bleomycin-induced pulmonary fibrosis. Interrupted reprogramming can be used as an
      alternative approach to produce highly specified functional therapeutic cell
      populations and may lead to significant advances in regenerative medicine.

PMID- 30210812
TI  - Acute medullar compression secondary to a septic arthritis of a thoracic facet
      joint: a case report and review of literature.
AB  - Introduction: Septic arthritis of a facet joint (SAFJ) is a rare entity and
      frequently underdiagnosed. It is most frequently localised in the lumbar segment.
      Case presentation: A 48-year-old woman presented at our emergency room with a
      chief complaint of lumbar pain and perineal hypoesthesia. An urgent lumbar
      Magnetic Resonance Imaging (MRI) was performed showing no signs of compressive
      pathology. Intravenous painkillers were administered improving her clinical
      symptoms, so she was discharged from the emergency department to be followed at
      our out-patient clinic. After 12 h, the patient presented again referring an
      acute loss of strength in her lower limbs and paresthesias at a T10 sensitive
      level. Due to the severity of the symptoms, we performed an urgent dorsal MRI
      that showed a septic arthritis of the left T8-T9 facet joint and an epidural
      abscess causing a medullar compression. Blood cultures were performed before
      surgical treatment. An urgent laminectomy of T8 and debridement of the abscess
      were performed. Intraoperative microbiology and blood cultures were positive for
      Streptococcus constellatus. After surgery, the patient presented a progressive
      improvement of her symptomatology. Discussion: Physicians should have in mind and
      rule out this clinical entity to avoid severe consequences that a misdiagnosed
      SAFJ could develop.

PMID- 30210813
TI  - 18F-FDG-PET/CT localizes intervertebral disc space infection following posterior
      lumbar interbody fusion surgery leading to successful retention of percutaneously
      inserted pedicle screws: a case report.
AB  - Introduction: Postoperative infection is a potentially devastating complication
      of spine surgery and an appropriate strategy and timely decision-making are
      essential for successful treatment of deep surgical site infection (SSI) after
      spinal instrumentation surgeries. However, there is a lack of consensus on
      implant removal or retention. We report on a case of deep SSI after posterior
      lumbar interbody fusion (PLIF) surgery in which we achieved clinical cure by
      debridement and removal of the interbody fusion cage without removing the
      percutaneously inserted pedicle screws (PPS). Case presentation: A case was a 53
      year-old woman with deep SSI after PLIF surgery using the PPS system at the L4-5
      level. Computed tomography (CT) showed no clear radiolucent line around the
      screws and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET)/CT
      demonstrated abnormal FDG uptake around the cages and no uptake around the
      pedicle screws. Intervertebral cages were removed and iliac bone grafts were
      inserted between the vertebral bodies, without removing the pedicle screws. The
      infection was cleared and bone fusion was achieved after the revision surgery.
      Discussion: Targeting active infection using FDG-PET/CT is considered useful in
      narrowing the surgical margins and determining whether to preserve
      instrumentation in revision surgery after SSI. PLIF using the PPS system could be
      useful in preventing the easy spread of infection from the intervertebral space
      to the insertion point of PPS through the interstitial space.

PMID- 30210814
TI  - Giant lumbar pseudomeningocele after revision lumbar laminectomy: a case report
      and review of the literature.
AB  - Introduction: Incidental durotomy is a relatively common complication of spine
      surgery. Prevalence ranges from 3 to 5% in primary and 7 to 17% in revision
      procedures. Despite this relatively common occurrence the subsequent development
      of pseudomeningoceles following lumbar spine surgery is reported to be between
      0.07 and 2%. Giant pseudomeningoceles (GP) are rare and therefore we report our
      experience with a case. Case presentation: We report a case of an iatrogenic GP
      post revision lumbar surgery that extended 19 cm in length. The patient underwent
      revision L3-S1 laminectomy, laminotomy, excision of pseudomeningocele and
      successful direct dura repair. Postoperatively, a subcutaneous seroma persisted.
      This was managed with surgical exploration and prolonged drainage. This led to
      reduction of the seroma and symptomatic improvement for the patient. Discussion:
      Incidental durotomy is a relatively common complication of spine surgery and if
      the durotomy is not addressed at the time of an operation a pseudomeningocele may
      develop. A pragmatic approach for GP is to individualise management based upon
      symptoms. Although GP are rare, prevention is likely the best approach. We
      outlined a structured approach to the management of an incidental dural leak that
      formed the largest reported pseudomeningocele reported to date.

PMID- 30210810
TI  - Impacts of bisphenol A (BPA) and phthalate exposures on epigenetic outcomes in
      the human placenta.
AB  - The placenta guides fetal growth and development. Bisphenol A (BPA) and
      phthalates are widespread environmental contaminants and endocrine disruptors,
      and the placental epigenetic response to these chemicals is an area of growing
      research interest. Therefore, our objective was to summarize research linking BPA
      or phthalate exposure to placental outcomes in human pregnancies, with a
      particular focus on epigenetic endpoints. In PubMed, studies were selected for
      review (without limiting start date and ending on 1 May 2018) if they reported
      any direct effects of BPA or phthalates on the placenta in humans. Collectively,
      available studies suggest that BPA and phthalate exposures are associated with
      changes to placental micro-RNA expression, DNA methylation, and genomic
      imprinting. Furthermore, several studies suggest that fetal sex may be an
      important modifier of placental outcomes in response to these chemicals. Studies
      in humans demonstrate associations of BPA and phthalate exposure with adverse
      placental outcomes. Moving forward, more studies should consider sex differences
      (termed "placental sex") in the measured outcomes, and should utilize appropriate
      statistical approaches to assess modification by fetal sex. Furthermore, more
      consistent sample collection and molecular outcome assessment paradigms will be
      indispensable for making progress in the field. These advances, together with
      improved non-invasive tools for measuring placental function and outcomes across
      pregnancy, will be critical for understanding the mechanisms driving placental
      epigenetic disruption in response to BPA and phthalates, and how these
      disruptions translate into placental and fetal health.

PMID- 30210815
TI  - Effects of tumor treating fields (TTFields) on glioblastoma cells are augmented
      by mitotic checkpoint inhibition.
AB  - Tumor treating fields (TTFields) are approved for glioblastoma (GBM) therapy.
      TTFields disrupt cell division by inhibiting spindle fiber formation. Spindle
      assembly checkpoint (SAC) inhibition combined with antimitotic drugs
      synergistically decreases glioma cell growth in cell culture and mice. We
      hypothesized that SAC inhibition will increase TTFields efficacy. Human GBM cells
      (U-87 MG, GaMG) were treated with TTFields (200 kHz, 1.7 V/cm) and/or the SAC
      inhibitor MPS1-IN-3 (IN-3, 4 uM). Cells were counted after 24, 48, and 72 h of
      treatment and at 24 and 72 h after end of treatment (EOT). Flow cytometry,
      immunofluorescence microscopy, Annexin-V staining and TUNEL assay were used to
      detect alterations in cell cycle and apoptosis after 72 h of treatment. The
      TTFields/IN-3 combination decreased cell proliferation after 72 h compared to
      either treatment alone (-78.6% vs. TTFields, P = 0.0337; -52.6% vs. IN-3, P =
      0.0205), and reduced the number of viable cells (62% less than seeded). There was
      a significant cell cycle shift from G1 to G2/M phase (P < 0.0001). The apoptotic
      rate increased to 44% (TTFields 14%, P = 0.0002; IN-3 4%, P < 0.0001). Cell
      growth recovered 24 h after EOT with TTFields and IN-3 alone, but the combination
      led to further decrease by 92% at 72 h EOT if IN-3 treatment was continued (P =
      0.0288). The combination of TTFields and SAC inhibition led to earlier and
      prolonged effects that significantly augmented the efficacy of TTFields and
      highlights a potential new targeted multimodal treatment for GBM.

PMID- 30210817
TI  - Contribution of autophagy to ocular hypertension and neurodegeneration in the
      DBA/2J spontaneous glaucoma mouse model.
AB  - Glaucoma is a progressive optic neuropathy characterized by axonal degeneration
      and retinal ganglion cells loss. Several factors have been postulated to play a
      role in glaucoma, elevated intraocular pressure (IOP) being the best well-known
      causative factor. The mechanisms leading to ocular hypertension and glaucoma are
      still not fully understood. An increasing number of evidence indicates a role of
      autophagy in the pathophysiological process of ocular hypertension and glaucoma.
      However, while all of the studies agree that autophagy is induced in RGCs in
      response to injury, autophagy was found to either protect or promote cell death
      depending on the experimental model used. In order to gain more insight into
      both, the role of autophagy in the pathogenesis of glaucoma and the effect of
      chronic IOP elevation in the autophagy pathway, we have investigated here for the
      first time autophagy in the iridocorneal angle region, retinal ganglion cell
      bodies, and ON axons in the spontaneous ocular hypertensive DBA/2J mouse glaucoma
      model and in the transgenic DBA/2J::GFP-LC3 mice, generated in our laboratory.
      Our results indicate decreased autophagic flux in the outflow pathway cells in
      the DBA/2J mice, characterized by increased levels of LC3-II and p62 together
      with a decrease in the lysosomal marker LAMP1, evaluated by western blot and
      immunofluorescence. Elevated presence of autophagic vacuoles in the DBA/2J and,
      in particular, in the DBA/2J::GFP-LC3 mice was also observed. Expression of the
      GFP-LC3 transgene was associated to higher cumulative IOP in the DBA/2J
      background. In addition to higher elevation in IOP, DBA/2J::GFP-LC3 were
      characterized by further RGCs and exacerbated axonal degeneration compared to
      DBA/2J. This was accompanied by the notable high presence of autophagic figures
      within degenerating axons. These results strongly suggest overactivation of
      autophagy as a potential cellular mechanism leading to ON degeneration in the
      chronic hypertensive DBA/2J mice.

PMID- 30210816
TI  - Cellular and molecular responses to acute cocaine treatment in neuronal-like N2a
      cells: potential mechanism for its resistance in cell death.
AB  - Cocaine is a highly abused drug that causes psychiatric and neurological
      problems. Its entry into neurons could alter cell-biochemistry and contribute in
      the manifestation of early pathological symptoms. We have previously shown the
      acute cocaine effects in rat C6 astroglia-like cells and found that these cells
      were highly sensitive to cocaine in terms of manifesting certain pathologies
      known to underlie psychological disorders. The present study was aimed to discern
      acute cocaine effects on the early onset of various changes in Neuro-2a (N2a)
      cells. Whole-cell patch-clamp recording of differentiated cells displayed the
      functional voltage-gated Na+ and K+ channels, which demonstrated the neuronal
      characteristics of the cells. Treatment of these cells with acute cocaine (1 h)
      at in vivo (nM to MUM) and in vitro (mM) concentrations revealed that the cells
      remained almost 100% viable. Cocaine administration at 6.25 MUM or 4 mM doses
      significantly reduced the inward currents but had no significant effect on
      outward currents, indicating the Na+ channel-blocking activity of cocaine. While
      no morphological change was observed at in vivo doses, treatment at in vitro
      doses altered the morphology, damaged the neurites, and induced cytoplasmic
      vacuoles; furthermore, general mitochondrial activity and membrane potential were
      significantly decreased. Mitochondrial dysfunction enabled the cells switch to
      anaerobic glycolysis, evidenced by dose-dependent increases in lactate and H2S,
      resulting unaltered ATP level in the cells. Further investigation on the
      mechanism of action unfolded that the cell's resistance to cocaine was through
      the activation of nuclear factor E2-related factor-2 (Nrf-2) gene and subsequent
      increase of antioxidants (glutathione [GSH], catalase and GSH peroxidase [GPx]).
      The data clearly indicate that the cells employed a detoxifying strategy against
      cocaine. On a broader perspective, we envision that extrapolating the knowledge
      of neuronal resistance to central nervous system (CNS) diseases could delay their
      onset or progression.

PMID- 30210818
TI  - Effects of p21 on adult hippocampal neuronal development after irradiation.
AB  - Inhibition of hippocampal neurogenesis is implicated in neurocognitive impairment
      after cranial irradiation. We recently demonstrated that disruption of neuronal
      development after DNA damage was regulated by p53. The cyclin-dependent kinase
      inhibitor 1 or p21, a downstream effector p53, mediates cell cycle arrest in
      response to DNA damage. There is evidence that p21 negatively regulates
      proliferation of neural progenitors (NPCs). Here we characterized the effects of
      p21 on disruption of neuronal development in the hippocampal dentate gyrus after
      irradiation. We irradiated young adult mice wild type (+/+) or knockout (-/-) of
      the Cdkn1a (p21) gene, and used different bromodeoxyuridine (BrdU) paradigms for
      cell fate mapping. The acute apoptotic response of NPCs in the subgranular zone
      of the dentate gyrus was independent of p21 after irradiation. In nonirradiated
      mice, p21 knockout resulted in an increase in neuroblast proliferation and
      neurogenesis. At 9 weeks after 5Gy, NPCs in the subgranular zone demonstrated
      increased p21 expression. Loss of newborn type-1 cells and disruption of
      hippocampal neurogenesis was evident at 9 weeks after irradiation, and these
      effects were independent of p21 genotype status. Within the developmental
      milestones of NPCs, irradiation resulted in loss of early intermediate NPCs (type
      2a cells) in wild-type mice, whereas the principal effect of irradiation with p21
      loss was culling of proliferating late intermediate (type-2b cells) and
      neuroblasts. These results suggest that p21 exerts differential effects on cell
      fate of NPCs after irradiation. p21 may serve to protect proliferating late NPCs
      but does not alter the ultimate inhibition of new neuron production after DNA
      damage.

PMID- 30210820
TI  - Lung volume reduction-a great chance for emphysema patients!

PMID- 30210821
TI  - Lung volume reduction surgery in hypercapnic patients: a single-center experience
      from China.
AB  - Background: Lung volume reduction surgery (LVRS) has shown early promise as a
      palliative therapy in severe emphysema, but with a controversy over its
      indications. The aim of this study was to evaluate whether patients with
      hypercapnia should be excluded from LVRS. Methods: Total 15 cases of severe
      emphysema with the level of PaCO2 exceeding 50 mmHg were retrospectively studied.
      Their basic characteristics, pulmonary function, preoperative and postoperative
      PaCO2 level as well as postoperative complications were calculated statistically.
      Results: All of the 15 patients received video-assisted thoracoscopic LVRS and
      finally discharged uneventfully from hospital after the surgical procedures. Nine
      cases were supported by mechanical ventilation after surgery with the median
      duration of 44 hours. One of them was treated by extracorporeal membrane
      oxygenation (ECMO) both during surgery and the first 4 days after surgery. The
      result of blood gas analysis on 3 months after hospital discharge decreased than
      that before surgery (60.07 vs. 55.61 mmHg, P=0.076), but without statistical
      significance. Conclusions: The emphysematous patients with hypercapnia should not
      be excluded from the benefits of LVRS.

PMID- 30210819
TI  - The TLR-4 agonist adjuvant, GLA-SE, improves magnitude and quality of immune
      responses elicited by the ID93 tuberculosis vaccine: first-in-human trial.
AB  - Tuberculosis (TB) is the leading cause of infectious death worldwide. Development
      of improved TB vaccines that boost or replace BCG is a major global health goal.
      ID93 + GLA-SE is a fusion protein TB vaccine candidate combined with the Toll
      like Receptor 4 agonist adjuvant, GLA-SE. We conducted a phase 1, randomized,
      double-blind, dose-escalation clinical trial to evaluate two dose levels of the
      ID93 antigen, administered intramuscularly alone or in combination with two dose
      levels of the GLA-SE adjuvant, in 60 BCG-naive, QuantiFERON-negative, healthy
      adults in the US (ClinicalTrials.gov identifier: NCT01599897). When administered
      as 3 injections, 28 days apart, all dose levels of ID93 alone and ID93 + GLA-SE
      demonstrated an acceptable safety profile. All regimens elicited vaccine-specific
      humoral and cellular responses. Compared with ID93 alone, vaccination with ID93 +
      GLA-SE elicited higher titers of ID93-specific antibodies, a preferential
      increase in IgG1 and IgG3 subclasses, and a multifaceted Fc-mediated effector
      function response. The addition of GLA-SE also enhanced the magnitude and
      polyfunctional cytokine profile of CD4+ T cells. The data demonstrate an
      acceptable safety profile and indicate that the GLA-SE adjuvant drives a
      functional humoral and T-helper 1 type cellular response.

PMID- 30210822
TI  - Improved postoperative lung function after sublobar resection of non-small-cell
      lung cancer combined with lung volume reduction surgery in patients with advanced
      emphysema.
AB  - Background: Radiotherapy is recommended as primary local therapy for inoperable
      patients with non-small cell lung cancer (NSCLC). We hypothesized that selected
      patients with advanced emphysema could be candidates for surgery and improved
      functional outcome might result in addition to low mortality and morbidity and
      successful cancer control when sublobar resection in a lung volume reduction
      surgery (LVRS) concept is applied. Methods: All patients with NSCLC and severe
      emphysema who underwent cancer resection in a LVRS concept between 2003 and 2015
      were included for analysis. Postoperative 90-day mortality, complications,
      survival and lung function with forced expiratory volume in one second pre
      operatively and three months postoperatively served as endpoints. Results:
      Fourteen patients were included. Three procedures were bilateral and eleven
      unilateral, eight have been performed with thoracoscopy and six with conversion
      to an open procedure due to adhesions. In ten patients, tumor resection was
      atypical and in four patients an anatomic segmentectomy was performed. All
      patients had lung volume reduction. Prolonged air leak occurred in three
      patients. Perioperative 90-mortality was zero. Median pre-operative forced
      expiratory volume in one second was 32.5% and increased to 37% (P=0.002) 3 months
      following surgery. Three and 5-year survival rates were 50% and 35%,
      respectively. Conclusions: Sublobar resection of NSCLC combined with LVRS in
      patients with severely impaired lung function due to emphysema can be performed
      with low mortality and morbidity making it an alternative treatment modality to
      radiotherapy. This approach allows cancer resection in marginal patients and
      improves emphysema symptoms simultaneously.

PMID- 30210823
TI  - Endobronchial coil therapy in severe emphysema: 6-month outcomes from a Swiss
      National Registry.
AB  - Background: Endobronchial coils have been demonstrated in three randomized,
      controlled trials to improve quality of life, exercise tolerance, and lung
      function in patients with severe emphysema. This therapy is CE-marked and
      commercially available in Switzerland. Coil treated patients are followed in a
      post-market Swiss registry to collect safety and effectiveness data in routine
      clinical practice. Methods: The Swiss coil registry was initiated in October
      2013. At the end of November 2016, an interim analysis of all 64 patients treated
      in five centers was performed to evaluate safety and effectiveness at six months
      post treatment. Results: patients had completed bilateral treatment with 6-month
      follow up at the time of data analysis. Patients had very severe, symptomatic
      emphysema and hyperinflation [38% male, mean age 66 years, BMI 24, FEV1 30%
      pred., residual volume (RV) 247% pred., 6-minute walking distance (6-MWD) 272 m,
      St. George Respiratory Questionnaire (SGRQ) 57 points]. Up to 6 months following
      treatment, seven serious adverse events (SAE) were reported in 6/29 patients. No
      device removals were necessary. At 6 months, responder rates [% achieving the
      minimal clinically important difference (MCID)] were as follows: RV (-0.35 L)
      76%; FEV1 (+10%) 57%; SGRQ (-4 points) 87%; 6MWD (+26 m) 60%. Conclusions:
      Endobronchial coil therapy performed in expert centers in Switzerland yields high
      6-month responder rates across all relevant outcome.

PMID- 30210824
TI  - Emphysema and lung volume reduction: the role of radiology.
AB  - Chronic obstructive pulmonary disease (COPD) is one of the leading causes of
      death worldwide. One of the main findings is pulmonary emphysema in association
      with chronic bronchitis. Clinical signs, pulmonary function tests and imaging are
      the current used methods to diagnose and stage emphysema. Lung volume reduction
      (LVR) and endoscopic lung volume reduction (ELVR) are the current therapeutic
      options beside lung transplantation in cases of severe emphysema. Nowadays
      imaging is one of the key factors for the success of these therapies. Especially
      quantitative computed tomography (CT) with its increasing possibilities has
      become a viable tool, providing detailed information about distribution and
      heterogeneity of emphysema. Other imaging techniques like dual-energy CT (DECT)
      and functional magnetic resonance (MR) have shown to add functional information.
      These structural and functional information support thoracic surgeons and
      interventional pulmonologists in selecting patients and optimizing LVR procedures
      but also enables the development of new endobronchial therapies. Imaging will
      further improve the individual outcome by supporting the choice of optimal
      therapy.

PMID- 30210825
TI  - Clinical management of lung volume reduction in end stage emphysema patients.
AB  - Following the evaluation of surgical lung volume reduction (LVR) in the National
      Emphysema Treatment (NETT) trial, different endoscopic LVR procedures have been
      developed for severe emphysema. Among those, endobronchial valve placement is the
      best evaluated method. All these therapies aim at reducing hyperinflation and at
      improving respiratory mechanics. It has been shown that these procedures can
      improve quality of life, lung function and exercise capacity in a significant and
      clinically meaningful way in suitable patients. Optimal medical therapy, physical
      rehabilitation, smoking cessation and respiratory insufficiency assessments
      should been thoroughly evaluated by a multi-disciplinary team before considering
      any LVR procedure. Clinical experience is necessary to decide if a patient is an
      appropriate candidate for a surgical or an interventional LVR procedure, to
      choose the optimal treatment strategy and to provide a high-level of care after
      the intervention, particularly when complications such as pneumothorax or
      persistent air leak occur in this already severely ill patient population. High
      volume emphysema care centers, providing a broad spectrum of different LVR
      procedures and involving a multidisciplinary team in the diagnostic process, are
      best suited to provide an optimal outcome. The aim of this manuscript is to
      describe the structures and procedures required to achieve the best possible
      outcome even in patients with advanced stage of their emphysema disease,
      including patients who are candidates for lung transplantation.

PMID- 30210827
TI  - Lung volume reduction surgery in the post-National Emphysema Treatment Trial era.
AB  - Lung volume reduction surgery (LVRS) as means to improve the pulmonary function
      and quality of life of patients with chronic obstructive pulmonary disease (COPD)
      can be traced back to the 1950's and early work by Otto Brantigan. Joel Cooper
      revived this concept with pioneering work in the 1990's. His work, along with
      others, led to the National Emphysema Treatment Trial (NETT) which demonstrated a
      quality of life and survival benefit for certain subsets of patients with
      emphysema. While the outcomes of carefully selected patients are excellent, with
      proven benefits in both quality of life and overall survival, the volume of LVRS
      being performed remains low. The procedure is highly regulated in the United
      States and is only performed in Centers for Medicare and Medicaid Services (CMS)
      approved programs. Programs are required to follow the NETT selection criteria.
      The program at Columbia University Medical Center/New York Presbyterian Hospital
      remains active. Utilizing the NETT criteria, we continue to perform LVRS with no
      operative mortality and excellent long-term outcomes.

PMID- 30210826
TI  - Anaesthesia management for bronchoscopic and surgical lung volume reduction.
AB  - Optimizing the patient's condition before the lung volume reduction (LVR)
      according to recommendations by American College of Cardiology/American Heart
      Association (ACC/AHA) guideline on perioperative cardiovascular evaluation is
      mandatory. Implementation of a multimodal analgesia concept and the use short
      acting anaesthetics enhances recovery and avoids postoperative pulmonary
      complications. Normovolemia, normothermia, lung protective ventilation and an
      evidence-based concept of airway management (i.e., double-lumen tube, bronchus
      blocker) are suggested for intraoperative management of surgical lung volume
      reduction (SLVR). General anaesthesia (using remifentanil, propofol and
      mivacurium) with an i-gel(r) supraglottic airway device should be used for
      bronchoscopic lung volume reduction (BLVR). Jet ventilation through rigid
      bronchoscopy or with a jet catheter may be an alternative concept. Experienced
      consultants should perform anaesthesia for LVR.

PMID- 30210828
TI  - Lung volume reduction surgery beyond the NETT selection criteria.
AB  - Lung volume reduction surgery (LVRS) for symptomatic patients with advanced
      emphysema was proven to be successful in a large randomized multi-center trial
      (NETT) and in several smaller randomized single center trials. This evidence
      primarily concerns patients with heterogeneous, upper-lobe predominant emphysema
      and low exercise tolerance within certain selection criteria regarding lung
      function values. As the most important effect of LVRS is generated by reducing
      the hyperinflation, even patients with homogeneous emphysema morphology profit
      from the procedure. Simultaneously, by removing distended and functionless areas
      in heterogeneous emphysema, also patients with seriously impaired diffusion
      capacity, moderate pulmonary arterial hypertension, a history of previous LVRS
      and alpha-1-antitrypsin-deficiency (AATD) can be considered as candidates for (re
      )-LVRS. This article summarizes indications for LVRS in these various subtypes of
      emphysema patients.

PMID- 30210829
TI  - Staged unilateral lung volume reduction surgery: from mini-invasive to minimalist
      treatment strategies.
AB  - Lung volume reduction surgery (LVRS) entailing unilateral or bilateral non
      anatomical resection of severely damaged emphysematous tissue carried out by
      thoracoscopic or open surgical approaches, under general anesthesia with single
      lung ventilation, has resulted in significant and long-lasting clinical and
      functional benefit. Unfortunately, the morbidity rates reported by simultaneous
      bilateral resectional LVRS has led to raise criticism regarding its cost
      effectiveness and has stimulated in recent years the development of less invasive
      bronchoscopic and surgical non-resectional methods of treatment that are
      preferentially performed in a staged unilateral fashion. We had previously
      proposed an innovative LVRS modality, which did not entail any resection of lung
      tissue and was electively carried out according to a staged unilateral strategy
      by a multiport thoracoscopic access, through thoracic epidural anesthesia in
      conscious, spontaneously ventilating patients (awake LVRS). The awake LVRS
      resulted in significant clinical benefit paralleling that achieved by the
      resectional method with lower morbidity rates and shorter hospital stay.
      Moreover, the awake LVRS proved also suitable to be employed in stringently
      selected patients to perform redo procedures following previous successful
      bilateral LVRS. More recently, in order to minimize the global surgery- and
      anesthesia-related traumas, we have modified our original non-resectional method
      by adopting a single thoracoscopic access as well as an anesthesia protocol
      entailing use of a simple intercostal block with target control sedation, to
      realize an ultra-minimally invasive or minimalist LVRS. Hence, a deeper
      investigation of the pros and cons of staged unilateral LVRS strategies as well
      as of the novel surgical non-resectional and redo LVRS is warranted in order to
      verify, the optimal strategies of treatment, which will prove to reduce the
      typical LVRS-related morbidity while assuring the most durable benefit in
      patients with advanced emphysema.

PMID- 30210831
TI  - Postoperative complications and management after lung volume reduction surgery.
AB  - The aim of lung volume reduction surgery (LVRS) for patients suffering from
      severe emphysema is to improve lung function and palliate dyspnea. Careful
      patient selection in a multidisciplinary approach in a high-volume center is
      mandatory for a successful outcome. Pulmonary complications including air leak
      and pneumonia as well as cardiac complications are the most common complications
      after LVRS. The following article will focus on most common complications
      observed after LVRS and review the management strategies to improve surgical
      outcome.

PMID- 30210830
TI  - Pulmonary hypertension in chronic obstructive pulmonary disease and emphysema
      patients: prevalence, therapeutic options and pulmonary circulatory effects of
      lung volume reduction surgery.
AB  - The exact prevalence of pulmonary hypertension (PH) and cor pulmonale (CP) in
      chronic obstructive pulmonary disease (COPD) is unknown, and varies considerably
      from 20-91%. Usually, mean pulmonary artery pressure (mPAP) does not exceed 30
      mmHg, and PH is not severe. However, PH and CP are important predictors of
      mortality in COPD and contribute to disability in this disease. Many factors
      contribute to the development of PH in chronic lung disease, including reduction
      of the pulmonary vascular cross-sectional area due to parenchymal loss and
      accompanying hypoxia, effects of abnormal pulmonary mechanics due to
      hyperinflation, but also vascular remodeling processes. So far, PH associated
      with chronic lung disease cannot be treated medically. Therefore, it is indicated
      to treat the underlying pulmonary disease. Patients with severe PH should be
      referred to centers experienced in the management of PH and enrollment in
      clinical trials should be considered. Lung volume reduction surgery (LVRS)
      theoretically further increases pulmonary vascular resistance (PVR) by reducing
      the vascular bed when resecting lung tissue, however, this might be compensated
      by better pulmonary mechanics through reduction of hyperinflation, which will be
      discussed in the present article.

PMID- 30210832
TI  - Valve therapy in patients with emphysematous type of chronic obstructive
      pulmonary disease (COPD): from randomized trials to patient selection in clinical
      practice.
AB  - In recent years a number of endoscopic methods have emerged to treat patients
      with severe emphysematous type of chronic obstructive pulmonary disease (COPD),
      who are primarily symptomatic due to hyperinflation despite optimal medical
      management. Of these techniques, implantation of endobronchial one-way valves
      into targeted airways of isolated emphysematous lobes appears to be one of the
      most promising innovations. Results from randomized controlled trials of valve
      therapy for emphysema show consistent benefits in terms of lung function,
      exercise capacity, symptoms, and quality of life. This review aims to provide a
      comprehensive summary of the currently available scientific data, discussion of
      typical treatment related side effects, and recommendations for patient selection
      in clinical practice.

PMID- 30210833
TI  - Lung volume reduction with endobronchial coils for patients with emphysema.
AB  - The lung volume reduction coil treatment is a minimally invasive bronchoscopic
      treatment option for emphysema patients who suffer from severe hyperinflation.
      The treatment is aimed at a large group of patients where lung volume reduction
      surgery and bronchoscopic lung volume reduction using endobronchial valves are no
      option, or alternatively, can be offered as a bridge to lung transplantation. The
      nitinol coil exhibits a shape memory effect and is biologically inert. The lung
      volume reduction coil procedure is performed in two separate treatment sessions,
      targeting one lobe per session, with the contralateral lobe being treated 4 to 8
      weeks after the first session. In one treatment session, around 10 to 14 coils,
      thereby treating an entire lobe, are being placed. Selecting optimally treated,
      symptomatic chronic obstructive pulmonary disease (COPD) patients with emphysema
      and severe hyperinflation, while avoiding significant airway disease such as
      asthma, chronic bronchitis and bronchiectasis, is key to achieve treatment
      success. Three randomized clinical trials investigating lung volume reduction
      coil treatment have been published until now, reporting the results of 452
      treated patients up to 12 months after coil treatment. Lung volume reduction coil
      treatment results in significant improvement of pulmonary function outcomes and
      quality of life in patients with severe hyperinflation. The most common
      complications of lung volume reduction coil treatment are: COPD exacerbations,
      pneumonia, Coil Associated Opacity and an increased risk of pneumothorax. The
      purpose of this article is to describe the coil technique and review the
      available literature regarding effect, safety and future perspectives of lung
      volume reduction with coils for emphysema patients.

PMID- 30210835
TI  - Complications after bronchoscopic lung volume reduction.
AB  - Bronchoscopic lung volume reduction (BLVR) has been demonstrated an efficient and
      safe alternative to surgery in multiple randomized trials and retrospective
      cohort studies. However, despite its minimal invasiveness BLVR is not without
      potential harm. Complications and their incidents differ significantly between
      the individual BLVR techniques (valves, coils, vapour or sealant) which are
      bearing varying device- and intervention-dependent risks. Interventional
      pulmonologists must be aware of potential side effects and their management to
      anticipate and ensure highest quality treatment of the severely ill emphysema
      patient.

PMID- 30210834
TI  - Thermic and chemical procedures for bronchoscopic lung volume reduction.
AB  - In the last 14 years several endoscopic procedures have been developed to offer
      patients with advanced chronic obstructive pulmonary disease (COPD) and emphysema
      further therapeutic options, complementary to a medical treatment. In addition to
      the established valve implantation, new approaches have been available since
      2009. These procedures include bronchoscopic thermal vapor ablation (BTVA) and
      polymeric lung volume reduction. Both therapies are independent of collateral
      ventilation (CV), are irreversible and can be used on segmental (BTVA) and sub
      segmental level [polymeric lung volume reduction (PLVR)], in contrast to valve
      therapy. The intention is to induce a local inflammation with a following
      fibrosis and shrinkage and thus a volume reduction in the treated lung areas.
      Currently, only patients with predominant upper-lobe emphysema are treated. An
      improvement of lung function, exercise capacity and quality of life could be
      proved in RCTs for BTVA as well as for PLVR. However, the data for PLVR is very
      limited and has recently been available only in studies. Furthermore, the risk
      profile is unfavourable with a high number of adverse respiratory events. While
      BTVA is an established new approach, the PLVR requires re-evaluation regarding
      materials, predictive factors, safety profile and dosage.

PMID- 30210836
TI  - Lung volume reduction surgery or bronchoscopic lung volume reduction: is there an
      algorithm for allocation?
AB  - Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death
      in the world with the annual number of deaths increasing every year. Alterations
      in chest wall mechanics, respiratory muscle mechanics, and impaired cardiac
      function that result from increased air-trapping are well known sequelae of COPD
      and contribute to increased morbidity and mortality. A reduction in
      hyperinflation can improve cardiopulmonary function. In selected patients with
      COPD and an emphysema phenotype, lung volume reduction surgery (LVRS) has
      demonstrated improvements in symptom burden and mortality. Minimally invasive
      bronchoscopic techniques that reduce end-expiratory lung volume have shown
      improvements in lung function, dyspnea and quality of life. In this review, we
      review selection criteria, risks, and benefits of surgical and bronchoscopic lung
      volume reduction (BLVR). Recommendations are provided to guide treatment
      decisions based on the current literature.

PMID- 30210837
TI  - The role of the multidisciplinary emphysema team meeting in the provision of lung
      volume reduction.
AB  - Despite a positive result in favour of lung volume reduction surgery (LVRS), from
      one of the largest randomized controlled trial in thoracic surgery, the
      identification of poor outcome in certain high-risk groups has resulted in a
      worldwide decrease in its utilization. Patient selection is the key to successful
      lung volume reduction which, with the advent of a range of less invasive
      techniques, has become more complex. The greater variety of potential therapeutic
      options will inevitably lead to debate amongst treating clinicians. Therefore, to
      be able to make an informed decision on the best treatment for an individual
      patient, discussion between clinicians in a multidisciplinary team (MDT) meeting
      is advisable. The membership of this MDT must include all specialists involved in
      assessment and subsequent treatment of the patient including non-medical input.
      There must be robust administrative organization and record of decisions together
      with inter-disciplinary communication of decisions. Whilst ultimately it is the
      patient who will benefit from the MDT, individual participants will enhance their
      continued professional development. The referral pathway into the MDT must be
      clearly defined and disseminated. Which investigations are to be performed by
      referrers and which by the specialist centre need to be in an agreed protocol.
      Specialist input may be required to interpret the results of the latest
      assessment tools. The decision-making process of the MDT begins with confirmation
      of basic selection criteria but addresses three main areas of discussion: the
      definition of target areas of lung for reduction; the presence of collateral,
      interlobar ventilation and an assessment of individualized risk and benefit. The
      emphysema or lung volume reduction MDT has been established in several specialist
      units and its benefits include an increase in referrals overall for LVR. The
      establishment of an MDT approach to lung volume reduction has now been
      incorporated into several national guidelines.

PMID- 30210838
TI  - Successful lung volume reduction surgery in combined pulmonary emphysema and
      fibrosis without body-plethysmographic hyperinflation-a case report.
AB  - Surgical and bronchoscopic lung volume reduction (LVR) have been demonstrated to
      improve lung function, dyspnea and quality of life in patients with severe
      pulmonary emphysema. The most important functional prerequisite for a successful
      LVR is hyperinflation measured by body plethysmography. A residual volume (RV) of
      more than 180% predicted and a RV/total lung capacity (TLC) ratio of more than
      0.58 were inclusion criteria in major LVR trials. Here we report a successful LVR
      in a 68-year-old man with advanced, heterogeneous emphysema without
      plethysmographic evidence of severe hyperinflation (RV/TLC 0.45). Computed
      tomography (CT) revealed severe, partly bullous upper lobe emphysema and subtle
      fibrotic changes with volume loss of lower lobes. Since lower lobes appeared
      compressed by upper lobe emphysema, these target areas were removed by
      thoracoscopic LVR. Four months later, the patient reported major improvements of
      dyspnea, FEV1 (by 1.27 L) and 6-minute walking distance (by 150 meters). LVR
      reduced total lung volume measured by CT-volumetry by 0.5 L and upper lobe volume
      by 1.85 L while lower lobe volume increased by +1.34 L. Low density volume (-950
      HU) reflecting emphysema was reduced by 1.73 L. We conclude that the opposing
      effects of emphysema and fibrosis resulted in a barely increase in total lung
      volume that was only slightly reduced by LVR. Nevertheless, resection of
      emphysematous target areas identified by quantitative CT analysis provided major
      clinical and physiologic improvements related to decompression of low-compliance
      lower lobe areas retracted by early fibrosis. Therefore, in the combined presence
      of severe, heterogeneously distributed emphysema and fibrosis, LVR may improve
      respiratory mechanics even if RV/TLC, an established body-plethysmographic
      predictor of LVR success is not severely elevated.

PMID- 30210839
TI  - Sleepy Drivers: High time for action.

PMID- 30210840
TI  - The Role of N-Acetylcysteine Supplementation on the Oxidative Stress Levels,
      Genotoxicity and Lineage Commitment Potential of Ex Vivo Murine Haematopoietic
      Stem/Progenitor Cells.
AB  - Objectives: The ex vivo maintenance of haematopoietic stem/progenitor cells
      (HSPCs) is crucial to ensure a sufficient supply of functional cells for research
      or therapeutic applications. However, when exposed to reactive oxygen species
      (ROS) in a normoxic microenvironment, HSPCs exhibit genomic instability which may
      diminish their quantity and quality. This study aimed to investigate the role of
      N-acetylcysteine (NAC) supplementation on the oxidative stress levels,
      genotoxicity and lineage commitment potential of murine haematopoietic
      stem/progenitor cells (HSPCs). Methods: This study was carried out at the
      Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia, between June 2016 and
      July 2017. Bone marrow cells were isolated from nine mice and cultured in a
      growth medium. Various concentrations of NAC between 0.125-2 MUM were added to
      the culture for 48 hours; these cells were then compared to non-supplemented
      cells harvested from the remaining three mice as the control group. A trypan blue
      exclusion test was performed to determine cell viability, while intracellular ROS
      levels and genotoxicity were determined by hydroethidine staining and comet
      assay, respectively. The lineage commitment potential of erythroid, myeloid and
      pre-B-lymphoid progenitor cells was evaluated via colony-forming cell assay.
      Results: NAC supplementation at 0.25, 0.5 and 2 MUM significantly increased cell
      viability (P <0.050), while intracellular ROS levels significantly decreased at
      0.25 and 0.5 MUM (P <0.050). Moreover, DNA damage was significantly reduced at
      all NAC concentrations (P <0.050). Finally, the potential lineage commitment of
      the cells was not significantly affected by NAC supplementation (P >0.050).
      Conclusion: The findings of this study indicate that NAC supplementation may
      potentially overcome the therapeutic limitations of ex vivo-maintained HSPCs.

PMID- 30210841
TI  - Asthma Clinics in Primary Healthcare Centres in Oman: Do they make a difference?
AB  - Objectives: This study aimed to determine the effect of newly established asthma
      clinics (ACs) on asthma management at primary healthcare centres (PHCs) in Oman.
      Methods: This retrospective cross-sectional study was conducted between June 2011
      and May 2012 in seven PHCs in the Seeb wilayat of Muscat, Oman. All >=6-year-old
      asthmatic patients visiting these PHCs during the study period were included.
      Electronic medical records were reviewed to determine which clinical assessment
      and management components had been documented. Results: A total of 452 asthmatic
      patients were included in the study. The mean age was 35 +/- 21 years old (range:
      6-95 years) and the majority (57%) were female. In total, 288 (64%) cases were
      managed at ACs and 164 (36%) were managed at general clinics (GCs). Significant
      differences were noted in the documentation of cases managed at ACs compared to
      those at GCs, including history-taking information regarding signs and symptoms
      (91% versus 19%; P <0.001), trigger factors (79% versus 16%; P <0.001) and a
      history of atopy (81% versus 17%; P <0.001), smoking (61% versus 7%; P <0.001),
      asthma exacerbations (73% versus 10%; P <0.001) or previous admissions (63%
      versus 10%; P <0.001). Furthermore, prescription rates of inhaled corticosteroids
      (72% versus 61%; P = 0.021) and short-acting beta-agonists (93% versus 82%; P =
      0.001) were significantly higher at ACs compared to GCs. Conclusion: Overall, the
      findings indicated that ACs have had a positive impact on asthma management at
      the studied PHCs.

PMID- 30210842
TI  - Daytime Sleepiness Among Young Adult Omani Car Drivers.
AB  - Objectives: Sleepiness and fatigue play significant roles in exacerbating the
      occurrence of car crashes. However, there is a dearth of studies examining the
      prevalence of sleepiness while driving among Omanis. This study aimed to
      determine the proportion of young Omani adults who confess to daytime sleepiness
      while driving and to investigate associations between gender, daytime sleepiness
      and risk of obstructive sleep apnoea syndrome (OSAS). Methods: This cross
      sectional study took place at the Sultan Qaboos University Hospital, Muscat,
      Oman, between May and July 2014 and included 600 young adult Omani non-commercial
      drivers. The Berlin Questionnaire and Epworth Sleepiness Scale (ESS) were
      distributed among the participants, along with additional questions about their
      sleeping habits. Associations between daytime sleepiness while driving and
      nocturnal sleep duration, risk of OSAS and gender were determined. Results: A
      total of 492 private vehicle drivers took part in the study (response rate: 82%),
      of which 50.4% were male. Overall, 124 Omanis (25.2%) reported experiencing
      daytime sleepiness while driving at least once per month. There was a significant
      association between nocturnal sleep duration of <6 hours and sleepiness while
      driving (P = 0.042). Female participants were significantly more likely to score
      >10 on the ESS, indicating a greater propensity for daytime sleepiness (P =
      0.006). However, male drivers were significantly more likely to report sleepiness
      while driving (P = 0.001). Conclusion: Sleepiness while driving was common among
      young male drivers in Oman and might be due to nocturnal sleep deprivation.
      Further studies are needed so that preventative measures can be developed.

PMID- 30210843
TI  - Evaluation of Mitotic Figures and Cellular and Nuclear Morphometry of Various
      Histopathological Grades of Oral Squamous Cell Carcinoma: Comparative study using
      crystal violet and Feulgen stains.
AB  - Objectives: The objectives of this study were to quantitatively estimate the
      number of mitotic figures (MFs) and evaluate the cellular and nuclear features of
      various histological grades of oral squamous cell carcinoma (OSCC) using Feulgen
      and 1% crystal violet stains. Methods: This case-control study took place at the
      Dr D. Y. Patil Dental College & Hospital in Mumbai, Maharashtra, India, between
      June and December 2016. A total of 51 samples were retrieved from the hospital
      archives. Of these, 15 well-differentiated, 15 moderately-differentiated and six
      poorly-differentiated OSCC samples formed the case group while 15 samples of
      normal gingival mucosa constituted the control group. Each sample was dyed using
      Feulgen and 1% crystal violet stains and the mitotic count, nuclear area (NA),
      cellular area (CA), nuclear perimeter (NP), cellular perimeter (CP) and nuclear
      to-cytoplasmic (N/C) ratio was calculated using computer-aided morphometry
      techniques. Results: The number of MFs visible per field was significantly higher
      in Feulgen-stained sections as compared to those stained with crystal violet (P =
      0.050). In addition, the NA, NP, CA and CP values and N/C ratios of samples in
      the experimental group increased significantly in accordance with an increase in
      OSCC grade (P <0.001). Conclusion: The Feulgen stain is more reliable than 1%
      crystal violet in terms of the selective staining of MFs. Moreover, the findings
      of this study indicate that computer-based morphometric analysis is an effective
      tool for differentiating between various grades of OSCC.

PMID- 30210844
TI  - Epidemiology, Outcomes and Coronary Angiography Findings of Patients Following
      Out-of-Hospital Cardiac Arrest: A single-centre experience from Oman.
AB  - Objectives: Out-of-hospital cardiac arrests (OHCAs) are a leading cause of death
      worldwide. However, data regarding the management and outcomes of affected
      patients are lacking in the Middle East. The current study aimed to present the
      angiographic findings and outcomes of patients presenting with OHCA in Muscat,
      Oman. Methods: This retrospective study took place between January 2012 and
      December 2016 at the Sultan Qaboos University Hospital (SQUH), Muscat, Oman. All
      adult patients who presented following an OHCA to the Emergency Department of
      SQUH during the study period were included. Demographic and clinical data were
      collected from electronic medical records. Results: A total of 216 patients were
      included in the study. The majority (63.9%) presented after having collapsed,
      while 22.3% presented with chest pains. Asystole was the most frequent initial
      cardiac rhythm (62.5%), with only 10% having ventricular
      tachycardia/fibrillation. Very few patients (1.4%) had received cardiopulmonary
      resuscitation (CPR) prior to presentation. In total, 85 patients (39.4%) returned
      to spontaneous circulation (RSC); of these, post-RSC electrocardiography revealed
      an ST-segment elevation in 41.2% and normal findings in 23.5%. There were 63
      patients who underwent coronary angiography, with 28 requiring stenting. Overall,
      13% of patients survived and were discharged, although three survivors suffered
      permanent hypoxic brain damage. Conclusion: The overall survival rate of patients
      who had experienced an OHCA was low. Education programmes should focus on the
      benefits of immediate CPR for individuals experiencing an OHCA, with more
      opportunities for CPR training to be made available to the general public in
      Oman.

PMID- 30210845
TI  - Attitudes of Non-Asthmatic Children Towards Their Asthmatic Peers: Influence of
      interactions with asthmatic relatives and peers.
AB  - Objectives: This study aimed to examine non-asthmatic children's acceptance of
      and attitudes towards their asthmatic peers in Jordan. Methods: This descriptive
      cross-sectional study was conducted between September 2015 and January 2016 among
      1,812 non-asthmatic children aged 9-13 years old at 10 schools in Zarqa, Jordan.
      Arabic versions of the Peers Attitude Towards Children with Asthma scale and the
      Asthma Knowledge Test for Children were used to assess attitudes towards children
      with asthma and asthma-related knowledge, respectively. Results: A total of 1,586
      children participated in the study (response rate: 87.5%). Of these, 158 (10%)
      and 399 (25.2%) children reported a family history of asthma or knew at least one
      person with asthma, respectively. Although 50.3% stated that they would sit next
      to such children in the classroom, only 34.9% reported that they would be friends
      with an asthmatic child. However, 73.1% of the non-asthmatic children believed
      that asthmatic children were not pretending to be ill and 61.4% believed that
      such children were not ill due to their own carelessness. Female non-asthmatic
      children (P <0.001), those with a family history of asthma (P = 0.004) and those
      who knew other individuals with asthma (P <0.001) had significantly more positive
      attitudes towards and acceptance of their asthmatic peers. In addition, age was
      significantly related to attitude scores (P <0.001). However, there was no
      correlation between asthma-related knowledge and the children's attitudes towards
      peers with asthma (P = 0.611). Conclusion: Previous interactions with asthmatic
      family members or peers were found to significantly influence non-asthmatic
      children's attitudes towards their asthmatic peers.

PMID- 30210846
TI  - Arabic Translation, Validation and Cultural Adaptation of the 7-Item Hamilton
      Depression Rating Scale in Two Community Samples.
AB  - Objectives: Depression is a common mental disorder, the severity of which is
      frequently assessed via interview-based clinical scales such as the 7-item
      Hamilton Depression Rating Scale (HAMD-7). The current study aimed to translate
      and examine the validity of an Arabic version of the HAMD-7 scale. Methods: This
      study took place between February and March 2016 in the Psychiatry Department of
      King Saud University, Riyadh, Saudi Arabia. The HAMD-7 scale was translated into
      Arabic using forward and backward translation methods. A total of 153 Arabic
      speakers were recruited to test the translated scale, including 57 medical
      students and 96 members of the general public. The Arabic version of the HAMD-7
      scale was completed by trained investigators during face-to-face interviews with
      the participants. In order to assess convergent validity, participants also
      completed an Arabic version of the self-assessed Patient Health Questionnaire-9
      (PHQ-9) scale. Subsequently, the test-retest reliability of the translated HAMD-7
      scale was evaluated two weeks later during a second interview. Results: Overall,
      HAMD-7 scores were positively correlated with PHQ-9 scores (r = 0.633-0.749).
      Moreover, the translated HAMD-7 scale proved to be reliable in terms of test
      retest reliability (intra-class correlation coefficient: 0.807; P <0.001). With
      regards to internal consistency, the Cronbach's alpha values ranged between 0.607
      0.756. Conclusion: The Arabic HAMD-7 scale was found to be reliable and valid
      among two samples of Arabic speakers in Saudi Arabia. However, further research
      among Arab-speaking patients diagnosed with depression is needed in order to
      establish its usefulness in assessing the severity of depressive symptoms.

PMID- 30210847
TI  - The Dundee Ready Education Environment Measure: A prospective comparative study
      of undergraduate medical students' and interns' perceptions in Oman.
AB  - Objectives: This study aimed to assess perceptions of the educational environment
      in Oman among medical undergraduate students and interns using the Dundee Ready
      Education Environment Measure (DREEM) tool. Methods: This cross-sectional study
      was conducted between October 2016 and April 2017 at the Oman Medical College
      (OMC), Sohar, Oman. A total of 737 medical undergraduate students and interns
      from the OMC and College of Medicine & Health Sciences of Sultan Qaboos
      University in Muscat, Oman, were invited to complete the DREEM questionnaire in
      the form of an online survey. Mean overall scores, subscale scores and individual
      item scores were subsequently compared between undergraduate students and
      interns. Results: A total of 418 undergraduate students and interns completed the
      survey (response rate: 56.7%). The mean overall DREEM score was 130.75 +/- 12.69.
      While interns had higher mean DREEM scores than undergraduate students, this
      difference was not significant (133.00 +/- 17.64 versus 128.50 +/- 15.53; P =
      0.326). The mean score percentages for the perceptions of learning (66.7% versus
      58.3%; P = 0.028) and perceptions of teachers (75% versus 68.2%; P = 0.038)
      subscales were significantly higher among OMC interns compared to undergraduate
      students from the same college. The perceptions of the environment subscale
      received the lowest mean score percentages among undergraduate students and
      interns from both colleges. Conclusion: Overall, medical undergraduate students
      and interns viewed the educational environment in Oman in a positive light. It is
      possible that undergraduate students' perceptions of the educational environment
      may become more favourable as they progress with their medical career and become
      interns.

PMID- 30210848
TI  - Cephalometric Norms in an Omani Adult Population of Arab Descent.
AB  - Objectives: This study aimed to establish cephalometric norms for an Omani
      population of Arab descent and to compare these with established cephalometric
      values for Caucasians. Methods: This cross-sectional study was conducted at the
      Military Dental Centre and Oman Dental College in Muscat, Oman, between May 2014
      and October 2016. A total of 150 Omani patients between 20-29 years old seeking
      orthodontic treatment were included. All participants had a symmetrical face,
      class I molar and canine relationships, proper intercuspation, a normal
      overjet/overbite (<3 mm) and mild spacing/crowding of the teeth (<=3 mm). Lateral
      cephalography was performed in centric occlusion with the lips relaxed and the
      head in a natural position. Cephalometric measurements were then compared with
      Eastman Standard norms. Results: The Omani subjects were found to have a slightly
      retrusive maxilla, an increased angle between the maxillary and mandibular planes
      and shorter facial heights in comparison to the Eastman Standard norms.
      Furthermore, incisor relations were edge-to-edge in nature and the interincisal
      angle was reduced, suggesting that the Omani subjects had more proclined
      incisors. In addition, the lips were more protrusive and the nasolabial angle was
      more obtuse. Conclusion: In the Omani sample, increased proclination of the
      incisors was observed in comparison to Eastman Standard norms. As such, slightly
      more proclined incisors should be considered acceptable and natural among Omani
      patients of Arab descent. The cephalometric findings of this study may be helpful
      in the diagnosis and treatment planning of orthodontic problems among Omanis of
      Arab descent.

PMID- 30210849
TI  - Characteristics of Critically-Ill Patients at Two Tertiary Care Hospitals in
      Sudan.
AB  - Objectives: Knowledge of intensive care unit (ICU) admission patterns and
      characteristics is necessary for the development of critical care services,
      particularly in low-resource settings. This study aimed to describe the
      characteristics of critically-ill patients admitted to ICUs in Sudan. Methods:
      This prospective observational study was conducted between February and May 2017
      in the ICUs of two government tertiary care hospitals in Khartoum, Sudan. A total
      of 100 consecutive adult patients admitted to the ICUs were included in the
      study. The patients' demographic and clinical characteristics and Acute
      Physiologic Assessment and Chronic Health Evaluation (APACHE II) scores upon
      admission were recorded, as well as the reason for admission, presence of any
      underlying comorbidities, interventional requirements like mechanical ventilation
      or haemodialysis, length of stay in the ICU and patient outcome. Results: Of the
      sample, 58% were female and 42% were male. The mean age was 47.4 +/- 18.3 years
      old. Upon admission, the mean APACHE II score was 14.2 +/- 9.6. In total, 54% of
      the patients had no known underlying comorbidities. The most common reasons for
      ICU admission were neurological diseases (27%), sepsis or infectious diseases
      (19%) and postoperative management (12%). Mechanical ventilation and
      haemodialysis were required by 35% and 11% of the patients, respectively. The
      average length of stay was 10.0 +/- 7.2 days and the mortality rate was 24%.
      Conclusion: Most of the patients admitted to the ICUs were middle-aged females
      with no known underlying comorbidities. Larger studies are necessary to provide a
      comprehensive understanding of the critical care needs of Sudanese hospitals.

PMID- 30210850
TI  - Perceptions of Plagiarism Among Medical and Nursing Students in Erbil, Iraq.
AB  - Objectives: The rapidly rising incidence of plagiarism among students at
      universities throughout the world requires attention. This study aimed to
      determine the extent to which medical and nursing students in Erbil, Iraq,
      plagiarise, their knowledge, understanding and perceptions of plagiarism and the
      underlying factors that may lead them to plagiarise. Methods: This cross
      sectional study was carried out between January and June 2017 among a sample of
      400 undergraduate medical and nursing students at Hawler Medical University in
      Erbil. Plagiarism-related data were collected through a specially designed self
      administered questionnaire. Results: In total, 280 (70%) medical students and 120
      (30%) nursing students were included in the study. The reported prevalence of
      plagiarism was 54.3%, with a slightly higher prevalence among male students
      compared to female students (54.9% versus 53.8%; P = 0.820) and medical students
      compared to nursing students (58.9% versus 43.3%; (P = 0.004). Alarmingly, 34.8%
      of the students did not know what plagiarism was, and only 28% were aware of the
      legal consequences of plagiarism. Reported reasons for plagiarising included
      laziness and the ease with which others' work could be plagiarised, confusion,
      cultural reasons and pressure to meet deadlines. Conclusion: There was a lack of
      understanding of plagiarism and its legal ramifications among undergraduate
      medical and nursing students in Erbil. The findings of this study indicate that
      there is an urgent need to increase students' understanding of plagiarism and its
      consequences so as to reduce the incidence of this type of academic misconduct.

PMID- 30210851
TI  - Different Strokes: A management dilemma.
AB  - Stroke is a common medical emergency resulting from numerous pathophysiological
      mechanisms and with varied clinical manifestations; as such, the diagnosis of
      stroke requires diligent clinical assessment. When different stroke syndromes
      occur in the same patient, it may cause a dilemma in terms of diagnosis and
      management. This continuing medical education article describes an interesting
      patient with recurrent neurological events, highlighting the complex
      pathophysiological processes associated with cerebrovascular syndromes. It offers
      readers the opportunity to apply their own basic neuroscience knowledge and
      clinical skills to solve the challenges encountered during the course of
      diagnosing and treating this patient. Specifically, the article aims to
      familiarise readers with an approach to diagnosing brainstem strokes and the
      diverse manifestations of a common stroke syndrome.

PMID- 30210852
TI  - Paliperidone Palmitate-Induced Delirium in an Adolescent with Schizophrenia: Case
      report.
AB  - Schizophrenia is a serious long-term mental disorder which usually presents in
      adolescence or early adulthood. However, poor adherence to oral antipsychotics
      can lead to relapse and rehospitalisation. We report an adolescent male with
      schizophrenia who was referred to the South London & Maudsley National Health
      Service Foundation Trust, London, UK, in 2015 due to worsening psychotic
      symptoms. Following poor compliance with oral medications, a four-week regimen of
      paliperidone palmitate long-acting injections was initiated, with an initial
      positive response. However, 10 days after the second dose, the patient developed
      severe acute-onset delirium with fluctuating levels of consciousness.
      Paliperidone palmitate was discontinued and the patient instead underwent a
      course of zuclopenthixol decanoate long-acting injections with a favourable
      outcome.

PMID- 30210853
TI  - Nasopharyngeal Salivary Gland Anlage Tumour: A rare cause of neonatal respiratory
      distress.
AB  - A salivary gland anlage tumour (SGAT) is a very rare type of benign tumour that
      usually presents in early infancy with respiratory distress which is exacerbated
      upon feeding. We report a full-term male neonate who was referred to the Al
      Nahdha Hospital, Muscat, Oman, in 2015 with severe neonatal respiratory distress
      due to a nasopharyngeal obstruction immediately after birth. Computed tomography
      and magnetic resonance imaging revealed a well-circumscribed mass in the
      nasopharynx, without intracranial extension. Histopathological analysis of the
      lesion confirmed a diagnosis of SGAT. Following excision of the tumour, the
      postoperative period was uneventful. No recurrence was observed over the next two
      years. This case report highlights the importance of the early recognition of
      this extremely rare and potentially life-threatening, yet easily curable,
      condition.

PMID- 30210855
TI  - Point-of-Care Airway Ultrasonography Prior to an Emergency Cricothyroidotomy:
      Case Report.
AB  - The use of ultrasonography in acute and critical care medicine is becoming
      increasingly common. However, use of an airway ultrasound as an adjunct to
      determine the type of intervention needed and assess complications is not common
      practice. We report a 56-year-old male who presented to the Emergency Department
      of the Sungai Buloh Hospital, Selangor, Malaysia, in 2015 with hoarseness,
      stridor and impending respiratory failure. A point-of-care ultrasound performed
      to assess the neck and vocal cords indicated a heterogeneous echogenic mass in
      the larynx, thus ruling out a cricothyroidotomy. The patient was therefore
      referred for an emergency tracheostomy. This case highlights the importance of
      point-of-care airway ultrasonography in the assessment of patients with stridor.
      This imaging technique not only helps to detect the cause of the stridor, but
      also to determine the feasibility of a cricothyroidotomy in emergency cases.

PMID- 30210854
TI  - Inflammatory Reactions to Red Tattoo Inks: Three cases highlighting an emerging
      problem.
AB  - In recent years, tattoos have become more commonplace. However, this can result
      in various inflammatory processes, the management of which can be challenging in
      daily clinical practice. Tattoo-related inflammatory reactions can comprise
      different patterns, including acute and immediate reactions, foreign body
      granulomas, sarcoid granulomas, isomorphic lesions, allergic contact dermatitis
      and photosensitivity. We report three cases who were referred to the Dermatology
      Outpatient Clinic of the Hospital Universitario San Cecilio, Granada, Spain, in
      2017 with various skin reactions in the red-ink areas of their tattoos. Screening
      was performed for infectious diseases like atypical mycobacterial infections and
      systemic processes such as sarcoidosis. A good therapeutic response was achieved
      in all cases. An adequate differential diagnosis is essential for the therapeutic
      management of this emerging health problem.

PMID- 30210856
TI  - Rituximab Treatment in Myasthaenia Gravis: Report of two paediatric cases.
AB  - Myasthaenia gravis (MG) is an auto-immune disease involving the postsynaptic
      receptors in the neuromuscular junction. The condition is characterised by
      fatigable weakness of the skeletal muscles and is uncommon in children.
      Acetylcholinesterase inhibitors and immune-modifying medications are usually
      considered the mainstay of treatment. However, these medications have to be given
      on a lifelong basis so that patients remain in remission; furthermore, drug
      related side-effects can have a major impact on quality of life. We report two
      paediatric cases who were treated for MG at the Sultan Qaboos University
      Hospital, Muscat, Oman, in 2007 and 2008, respectively. Rituximab was eventually
      administered to each patient after their condition failed to improve despite
      several years of standard treatment with acetylcholinesterase inhibitors and
      immune-modifying medications. Overall, rituximab resulted in complete remission
      in one case and significant clinical improvement in the other case.

PMID- 30210858
TI  - Pulmonary Glue Embolism: An unusual complication following endoscopic
      sclerotherapy for gastric varices.
AB  - A pulmonary glue embolism is an unusual but potentially life-threatening
      complication following the treatment of variceal bleeding, especially in patients
      with large varices requiring large volumes of sclerosant. Other contributory
      factors include the rate of injection and ratio of the constituent components of
      the sclerosant (i.e. n-butyl-cyanoacrylate and lipiodol). This condition may be
      associated with a delayed onset of respiratory compromise. Therefore, a high
      degree of clinical suspicion is essential in patients with unexplained
      cardiorespiratory decline during or following endoscopic sclerotherapy. We report
      a 65-year-old man who was admitted to the Hull Royal Infirmary, Hull, UK, in 2017
      with haematemesis and melaena. He subsequently developed acute respiratory
      distress syndrome secondary to a glue embolism following emergency sclerotherapy
      for bleeding gastric varices. The aetiology of the embolism was likely a
      combination of the large size of the gastric varices and the large volume of
      cyanoacrylate needed. After an endoscopy, the patient underwent transjugular
      intrahepatic portosystemic shunting twice to control the bleeding, after which he
      recovered satisfactorily.

PMID- 30210857
TI  - Recurrent Dermatofibrosarcoma Protuberans with Pigmentation and Myoid
      Differentiation.
AB  - Dermatofibrosarcomas protuberans (DFSP) are rare low-grade tumours with various
      subtypes and usually occur among middle-aged adults. However, myoid
      differentiation is very rare. We report a 44-year-old woman who presented to the
      Lok Nayak Jai Prakash Hospital, New Delhi, India, in 2017 with a recurrent
      pigmented DFSP presenting as an arm swelling. Upon histological and
      immunohistochemical analysis, myoid differentiation was confirmed. A literature
      review of the clinical and histopathological features of this rare entity is
      presented.

PMID- 30210860
TI  - Mycoplasma pneumoniae Pneumonia with Worsening Pleural Effusion Despite Treatment
      with Appropriate Antimicrobials: Case report.
AB  - Mycoplasma pneumoniae is a common cause of community-acquired pneumonia. As M.
      pneumoniae pneumonia is usually a mild and self-limiting disease, complications
      such as pleural effusion occur only rarely. We report a 22-year-old woman who
      presented to the Emergency Medicine Department of the Sultan Qaboos University
      Hospital, Muscat, Oman, in 2017 with an eight-day history of fever associated
      with coughing, chills and rigors. She was diagnosed with M. pneumoniae pneumonia,
      but subsequently developed pleural effusion which worsened despite treatment with
      appropriate antimicrobials. The pleural effusion required drainage, which
      revealed that it was of the more severe exudative type. Following drainage, the
      patient improved dramatically. She was discharged and advised to continue taking
      antibiotics.

PMID- 30210859
TI  - Pulmonary Alveolar Microlithiasis: A commonly misdiagnosed rare entity.
AB  - Pulmonary alveolar microlithiasis (PAM) is an uncommon entity which can pose a
      diagnostic challenge. We report a 45-year-old female who was referred to the All
      India Institute of Medical Sciences, Bhopal, India, in 2017 with a two-year
      history of progressively worsening dyspnoea and dry coughing. She had been
      previously diagnosed with pulmonary tuberculosis elsewhere and prescribed
      antitubercular therapy; however, there was little improvement in her symptoms.
      Following referral, the patient was diagnosed with PAM based on high-resolution
      computed tomography findings and the abundance of lamellar microliths in a
      bronchoalveolar lavage sample. She was subsequently managed symptomatically and
      enrolled in a rehabilitation programme.

PMID- 30210861
TI  - Uremic Leontiasis Ossea.

PMID- 30210862
TI  - Thoracic Endometriosis Presenting with Bilateral Hydropneumothorax.

PMID- 30210863
TI  - 'Spoon-Fed' Versus Self-Directed Learning in an Arab Context.

PMID- 30210864
TI  - Re: Controversies in Odontogenic Tumours: Review.

PMID- 30210866
TI  - Retraction Notice: Diabetes-Related Knowledge and Preventative Practices Among
      Government Employees with Diabetes in Kuwait.
AB  - [This retracts the article on p. e444 in vol. 17, PMID: 29372087.].

PMID- 30210865
TI  - Re: Small-Cell Neuroendocrine Carcinoma of the Cervix Masquerading as a Cervical
      Fibroid: Report of a rare entity.

PMID- 30210868
TI  - New Strategies for Treatment of Diabetic Macular Edema.

PMID- 30210867
TI  - The Utility of Intraoperative Near Infrared Fluorescence (NIR) Imaging with
      Indocyanine Green (ICG) for the Assessment of Kidney Allograft Perfusion.
AB  - Background: Near infrared light (NIR) fluorescence imaging with indocyanine green
      (ICG) has been used in various aspects of surgery, such as in the assessment of
      vascular anastomosis, tissue perfusion, and the identification of lymph nodes. In
      this study we evaluated the utility of NIR/ICG fluorescence imaging in kidney
      transplantation. Materials and Methods: NIR/ICG imaging was used to assess
      allograft perfusion in n=1 living donor (LDRT) and n=2 deceased donor (DDRT)
      renal transplantations, performed in February 2017. The allograft arterial and
      venous anastomoses were done end-to-side to the corresponding recipient external
      iliacs, and ureteroneocystostomies were performed for urinary reconstructions.
      After completion of vascular anastomosis, ICG was given as intravenous bolus at
      0.3mg/kg, followed by visual assessment of tissue perfusion and vascular
      anastomoses at 1-minute interval using fluorescence imaging (KARL STORZ NIR/ICG
      System). Results: Homogenous global fluorescence of the allograft and vascular
      anastomosis was observed in all 3 cases. Immediate postoperative perfusion
      studies showed patent inflow and outflow vessels and well perfused transplanted
      kidneys. Immediate graft function was observed in 2 recipients (1 LDRT and 1
      DDRT). One session of haemodialysis was performed in 1 DDRT recipient, for high
      serum potassium in the immediate postoperative setting, who otherwise had good
      urine output and serially declining serum creatinine. Conclusions: NIR/ICG
      fluorescence imaging can be useful in renal transplantation for the
      intraoperative assessment of allograft perfusion, especially in complex cases
      with multiple renal arteries and vascular reconstructions.

PMID- 30210869
TI  - Ocular Surface Disease: Advances in Diagnostics and Therapeutics.

PMID- 30210870
TI  - Effects of Residual Anterior Lens Epithelial Cell Removal on Axial Position of
      Intraocular Lens after Cataract Surgery.
AB  - Purpose: The aim of this study was to assess the effects of residual anterior
      lens epithelial cell (LEC) removal by anterior capsule polishing on the effective
      lens position (ELP) and axial position stability of the intraocular lens (IOL)
      after cataract surgery via postoperative measurement of the anterior chamber
      depth. Methods: We enrolled 30 patients (60 eyes) requiring bilateral cataract
      surgery for age-related cataracts. Meticulous anterior capsule polishing and
      removal of residual LECs under the capsule were performed using a bimanual
      irrigation/aspiration system for one randomly selected eye in each patient. The
      eye without polishing served as a control. ELP was measured at five different
      time points after surgery, and axial shifting of IOL was determined at each visit
      by comparison with the position at the previous visit. Results: The polishing and
      control groups showed significant differences with regard to the mean ELP at 1
      (3.40 +/- 0.29 versus 3.53 +/- 0.32 mm, resp.; p=0.026) and 2 months (3.42 +/-
      0.32 versus 3.61 +/- 0.35 mm, resp.; p=0.001) after surgery, the mean standard
      deviation for the five ELP values (0.087 +/- 0.093 versus 0.159 +/- 0.138 mm,
      p=0.001), and the root mean square of the change in ELP at each follow-up visit
      (0.124 +/- 0.034 versus 0.246 +/- 0.038 mm, p=0.047). The eyes in the control
      group exhibited a tendency for backward IOL movement with a concurrent hyperopic
      shift in refraction of approximately 0.2 diopter at 2 months after surgery.
      Conclusion: Our findings suggest that residual anterior LEC polishing enhances
      the axial position stability of IOLs, without any complications, after cataract
      surgery.

PMID- 30210872
TI  - Participant Perspectives of Cognitive Rehabilitation for Type 2 Diabetes:
      Expectations and Impact.
AB  - Purpose: To describe the experiences of people with type 2 diabetes who have
      completed a comprehensive cognitive rehabilitation intervention. Method: Nineteen
      participants with type 2 diabetes enrolled in an 8-week intervention consisting
      of 4 educational classes to learn strategies to improve cognitive function and an
      online training program at home to practice cognitively stimulating activities.
      Two focus groups were conducted as part of a study designed to assess the
      feasibility of the comprehensive cognitive rehabilitation intervention. Results:
      Three main themes were identified in the qualitative data: (1) expectations of
      cognitive change; (2) use of cognitive strategies; and (3) effect on diabetes
      self-management. Participants shared valuable insight into how their experiences
      with the intervention changed and how they viewed diabetes. Conclusions: While
      the participants did not initially tie their cognitive complaints to diabetes,
      they were able to show how and why they might use cognitive strategies to improve
      diabetes self-management activities. By adapting those strategies for diabetes,
      quality of life can improve as well as potentially glycemic control.

PMID- 30210873
TI  - Do Robotics and Virtual Reality Add Real Progress to Mirror Therapy
      Rehabilitation? A Scoping Review.
AB  - Background: Mirror therapy has been used in rehabilitation for multiple
      indications since the 1990s. Current evidence supports some of these indications,
      particularly for cerebrovascular accidents in adults and cerebral palsy in
      children. Since 2000s, computerized or robotic mirror therapy has been developed
      and marketed. Objectives: To map the extent, nature, and rationale of research
      activity in robotic or computerized mirror therapy and the type of evidence
      available for any indication. To investigate the relevance of conducting a
      systematic review and meta-analysis on these therapies. Method: Systematic
      scoping review. Searches were conducted (up to May 2018) in the Cochrane Library,
      Google Scholar, IEEE Xplore, Medline, Physiotherapy Evidence Database, and
      PsycINFO databases. References from identified studies were examined. Results: In
      sum, 75 articles met the inclusion criteria. Most studies were publicly funded
      (57% of studies; n = 43), without disclosure of conflict of interest (59% of
      studies; n = 44). The main outcomes assessed were pain, satisfaction on the
      device, and body function and activity, mainly for stroke and amputees patients
      and healthy participants. Most design studies were case reports (67% of studies;
      n = 50), with only 12 randomized controlled trials with 5 comparing standard
      mirror therapy versus virtual mirror therapy, 5 comparing second-generation
      mirror therapy versus conventional rehabilitation, and 2 comparing other
      interventions. Conclusion: Much of the research on second-generation mirror
      therapy is of very low quality. Evidence-based rationale to conduct such studies
      is missing. It is not relevant to recommend investment by rehabilitation
      professionals and institutions in such devices.

PMID- 30210874
TI  - Clinical and Radiological Outcomes of Extracorporeal Shock Wave Therapy in Early
      Stage Femoral Head Osteonecrosis.
AB  - Objective: Femoral head osteonecrosis is a progressive clinical condition with
      significant morbidity and long-term disability. Several treatment modalities
      including both surgical and nonsurgical options have been used with variable
      levels of success. High-energy extracorporeal shock wave therapy is a
      nonoperative treatment option that has been described for early-stage disease. We
      aimed to assess the functional and radiological outcomes of extracorporeal
      shockwave therapy (ESWT) in the treatment of osteonecrosis of the femoral head
      (ONFH). Methods: Thirty-three hips of 21 patients were included in this study.
      Adult patients with ONFH of any etiology and in the precollapse stage were
      included. Clinical (visual analogue scale [VAS] and Harris hip score [HHS]) and
      radiological (plain radiographs and magnetic resonance imaging [MRI]) evaluations
      were performed before and after intervention. We used 3000-4500 pulses in a
      single session performed under general anesthesia. Results: At an average of 8
      months after ESWT, pain scores and HHS were significantly improved compared with
      the preintervention scores (p<0.001). The overall clinical outcomes were improved
      in 21 hips (63.3%), unchanged in 5 hips (15.15%), and worsened in 7 hips (21.2%).
      A trend toward a decrease in the size of the ONFH was observed although not of
      clinical significance (p=0.235). MRI revealed significant resolution of bone
      marrow edema (p<0.003). Regression was observed in 9 lesions (42.9%) and
      progression in 1 lesion (4.7%); no change was observed in the remaining 23
      lesions (52.4%). Conclusion: ESWT is a viable noninvasive treatment option for
      early-stage ONFH. It significantly improves clinical outcomes and may halt or
      delay the radiographic progression of the disease in the precollapse stage.

PMID- 30210875
TI  - Erratum to "Quadratus Lumborum Block as Sole, Homeostatic-Preserving Anesthetic
      for a Patient with Multiple System Atrophy Undergoing Open Inguinal Hernia
      Repair: A Case Report".
AB  - [This corrects the article DOI: 10.1155/2018/7161860.].

PMID- 30210876
TI  - Sick Sinus Syndrome and Takotsubo Cardiomyopathy.
AB  - Background. Takotsubo cardiomyopathy is associated with increased risk of
      ventricular arrhythmias, atrial fibrillation, and bradyarrhythmias. However,
      sinus node dysfunction is relatively infrequent in the setting of takotsubo
      cardiomyopathy. Case Report. We are reporting a case of a 73-year-old woman with
      a history of asymptomatic sinus bradycardia who developed sick sinus syndrome
      complicated by takotsubo cardiomyopathy. Conclusion. Acute symptomatic sick sinus
      syndrome in patients with preexisting silent sinus node dysfunction can trigger
      takotsubo cardiomyopathy. Understanding precipitating factors of takotsubo
      cardiomyopathy and identifying the patients at risk of life-threatening
      arrhythmia can help in refining risk stratification and therapy planning.
      Patients with sick sinus syndrome complicated by takotsubo cardiomyopathy may
      benefit from pacemaker implantation. However, evaluation on a case-by-case basis
      is mandatory.

PMID- 30210877
TI  - His-Bundle Pacing in a Patient with Transcatheter Aortic Valve Implantation
      Induced Left Bundle Branch Block.
AB  - Transcatheter aortic valve implantation (TAVI) is an effective intervention for
      severe aortic stenosis in patients at intermediate or high surgical risk, but
      damage to the native conduction system such as left bundle branch block (LBBB)
      may offset its benefits. New onset LBBB is associated with a higher risk of
      cardiovascular morbidity and mortality. His-bundle pacing (HBP) may be useful to
      treat TAVI-induced LBBB but has yet to be reported. We present the case of a 76
      year-old man with severe symptomatic aortic stenosis treated with TAVI. His
      preoperative electrocardiogram showed sinus rhythm with a narrow QRS complex.
      Insertion of a CoreValve Evolut R transcatheter aortic valve was uneventful apart
      from the development of LBBB with a long PR interval. A dual-lead DDD pacemaker
      was implanted via the left cephalic vein on the following day. HV was mildly
      prolonged at 60 ms. Capture of the proximal His restored AV synchrony without
      correction of LBBB. Repositioning of the lead with capture of the left bundle
      branch enabled complete ventricular resynchronisation with a single lead. Our
      case demonstrates that LBBB in the setting of TAVI may be corrected by HBP.

PMID- 30210878
TI  - A Long-Term Survivor with Tetralogy of Fallot Treated Only with the Classical
      Blalock-Taussig Shunt.
AB  - The prognosis of tetralogy of Fallot (TOF) treated only with Blalock-Taussig
      shunt (BTS) operation is unclear. A woman with TOF underwent classic BTS
      operation at 10 years of age. Despite no medication, she delivered two children
      and worked without apparent heart failure. At 72 years of age, she complained of
      dyspnea on exertion and leg edema. The cardiac angiogram revealed a well-patent
      BTS and severely stenotic right ventricular outflow tract. Right heart
      catheterization showed adequately maintained pulmonary blood flow with slight
      pulmonary arterial hypertension. Her unexpected yet favorable outcome reaffirms
      the importance of structural and functional self-adaptation even with cyanosis.
      If she had undergone a valve-sparing corrective surgery in adolescence, much
      better quality of life and outcome could have been expected.

PMID- 30210879
TI  - Management of Crown-Root Fracture in Primary Canine by Surgical Extrusion: A Case
      Report with 1-Year Follow-Up.
AB  - Complicated crown-root fractures of primary teeth often present with a greater
      challenge to the pediatric dentist. Extraction of the involved tooth is the
      routine treatment indicated. But, early loss of this primary tooth may lead to
      esthetic and psychological problems and also causes a detrimental effect on the
      development of occlusion and the alveolar bone. The present case report described
      the management of crown-root fracture in a primary canine by surgical extrusion
      and showed a satisfactory prognosis at one-year follow-up.

PMID- 30210871
TI  - The Impact of Egg Nutrient Composition and Its Consumption on Cholesterol
      Homeostasis.
AB  - Nutrient deficiencies and excess are involved in many aspects of human health. As
      a source of essential nutrients, eggs have been used worldwide to support the
      nutritional needs of human societies. On the other hand, eggs also contain a
      significant amount of cholesterol, a lipid molecule that has been associated with
      the development of cardiovascular diseases. Whether the increase of egg
      consumption will lead to elevated cholesterol absorption and disruption of
      cholesterol homeostasis has been a concern of debate for a while. Cholesterol
      homeostasis is regulated through its dietary intake, endogenous biosynthesis,
      utilization, and excretion. Recently, some research interests have been paid to
      the effects of egg consumption on cholesterol homeostasis through the intestinal
      cholesterol absorption. Nutrient components in eggs such as phospholipids may
      contribute to this process. The goals of this review are to summarize the recent
      progress in this area and to discuss some potential benefits of egg consumption.

PMID- 30210881
TI  - Digital Ischemia as an Unusual Manifestation of Hodgkin's Lymphoma.
AB  - Digital ischemia is associated with atherosclerotic, thromboembolic, or
      connective tissue diseases. Less often, it can be related to malignancy.
      Paraneoplastic vascular acrosyndromes (Raynaud's syndrome, acrocianosis, and
      acronecrosis) are associated with adenocarcinoma and less frequently with
      hematological malignancies. We report the case of a 45-year-old male, smoker,
      with a 10-day history of pain, cyanosis, and progressive digital necrosis in both
      hands. In the previous four months, he noticed painless mass in the right
      axillary gap, drenching night sweats, and weight loss. Physical examination at
      admission highlighted necrotic lesions on the distal phalanges of both hands
      (except the thumbs), enlarged lymph nodes in right axillary, and right
      supraclavicular gaps. Arteriography of upper limbs demonstrated a distal stop in
      all bilateral digital arteries. Digital ischemia was interpreted as a
      paraneoplastic phenomenon after other common etiologies were ruled out.
      Amputation of three phalanges was required due to necrosis. Biopsy of axillary
      nodes demonstrated nodular sclerosis classical Hodgkin's lymphoma (HL). The
      patient started conventional ABVD protocol (doxorubicin, bleomycin, vinblastine,
      and dacarbazine). After 6 cycles, he remained asymptomatic and symptoms of
      digital ischemia were completely resolved. It was concluded that the presence of
      acral vascular syndromes should alert the physician about the possibility of
      underlying malignant disease. Prompt investigation and treatment should be
      rapidly performed to avoid digital sequelae.

PMID- 30210880
TI  - Pancreaticopleural Fistula: A Review of Imaging Diagnosis and Early Endoscopic
      Intervention.
AB  - A 49-year-old male with history of chronic alcohol-induced pancreatitis presented
      with one month of worsening left pleuritic chest pain and shortness of breath.
      Chest radiograph demonstrated bilateral pleural effusions. Thoracentesis revealed
      increased amylase in the pleural fluid. Computed tomography (CT) and magnetic
      resonance cholangiopancreatography (MRCP) showed a fistula tract between the left
      pleural cavity and pancreas which was confirmed on endoscopic retrograde
      cholangiopancreatography (ERCP). Patient was treated with placement of a
      pancreatic stent with complete resolution of the fistula tract approximately in 9
      weeks. A systematic literature search was performed on reported cases with
      pancreaticopleural fistula (PPF) who underwent early therapeutic endoscopy within
      the last 10 years. Imaging modalities, particularly CT and MRCP, play essential
      role in prompt preprocedural diagnosis of PPF. Early therapeutic ERCP is an
      effective and relatively safe treatment option for PPF, so invasive surgery may
      be avoided.

PMID- 30210882
TI  - The Spiraling Case of a Yellow Chef: Isolated Hyperbilirubinemia.
AB  - Leptospirosis is a common bacterial disease in tropical regions of the world due
      to greater exposure to rodents and domestic animals; however, this condition can
      also occur in US urban areas, though it often goes unrecognized. Gastrointestinal
      symptoms are very commonly seen, and icteric leptospirosis is often confused for
      other conditions resulting in delayed diagnosis and worse outcomes. As mortality
      increases with more extensive hepatic involvement, gastroenterologists should be
      aware of the constellation of gastrointestinal symptoms related to leptospirosis,
      as it can occur in the absence of classic exposure history.

PMID- 30210883
TI  - Bartonella Endocarditis Mimicking Crescentic Glomerulonephritis with PR3-ANCA
      Positivity.
AB  - Bartonella henselae is a fastidious organism that causes cat scratch disease,
      commonly associated with fever and lymphadenopathy but, in rare instances, also
      results in culture-negative infectious endocarditis. We describe a patient who
      presented with flank pain, splenic infarct, and acute kidney injury with an
      active urinary sediment, initially suspicious for vasculitis, which was
      subsequently diagnosed as B. henselae endocarditis. Bartonella endocarditis may
      present with a crescentic glomerulonephritis (GN) and elevated PR3-ANCA antibody
      titers, mimicking ANCA-associated GN, with 54 cases reported in the literature.
      Unique to our case in this series is a positive PR3-ANCA antibody despite a
      negative IIF-ANCA. Thus, the presentation of Bartonella can mimic ANCA-associated
      GN, and renal biopsy showing immune complex deposition is critical for diagnosis
      and appropriate treatment.

PMID- 30210885
TI  - Profound Trunnion Wear Resulting in Femoral Head-Neck Dissociation in Total Hip
      Arthroplasty.
AB  - We describe a case of aseptic failure with profound femoral stem trunnion wear
      and femoral head dissociation nine years after initial primary total hip
      arthroplasty (THA) with the Stryker Accolade total hip arthroplasty system.
      Current guidelines for postoperative care and follow-up after THAs as potential
      intervention points for early detection of prosthetic joint failure are also
      reviewed.

PMID- 30210884
TI  - Spontaneous Macular Hole Closure after Valsalva Retinopathy and Nd:YAG Laser
      Treatment.
AB  - Purpose: The purpose of this report is to present a case who had spontaneous
      macular hole closure after Nd:YAG laser membranotomy applied to premacular
      haemorrhage associated with Valsalva retinopathy. Methods: Case report. Results:
      A 19-year-old young male patient presented to our clinic with sudden vision loss
      in his right eye, which had occurred 2 weeks before, following push-up and sit-up
      exercise. The patient was found to have premacular haemorrhage associated with
      Valsalva retinopathy. Nd:YAG laser membranotomy was performed. During his follow
      up at week 1, full-thickness MH was observed and he was put under observation. At
      month 6, his vision acuity improved, laser coagulation sites in the fundus
      disappeared, and macular hole closed spontaneously. Conclusion: Macular hole that
      develops after Nd:YAG laser treatment of Valsalva retinopathy may spontaneously
      be closed like in our case. However, there is a need for further research to
      understand the mechanism of closure.

PMID- 30210886
TI  - Minimally Invasive Treatment for Tibial Malrotation after Locked Intramedullary
      Nailing.
AB  - Rotational malreduction is a potential complication of intramedullary nailing for
      tibial shaft fractures. We experienced a symptomatic case of a 24 degrees 
      externally rotated malunion that we treated with minimally invasive corrective
      osteotomy. A 49-year-old man sustained a tibial shaft spiral fracture with a
      fibula fracture. He had been initially treated elsewhere with a reamed statically
      locked intramedullary nail. Bone union had been obtained, but he complained of
      asymmetry of his legs, difficulty walking and running, and the inability to ride
      a bicycle. We decided to perform corrective osteotomy in a minimally invasive
      fashion. After a 1 cm incision was made at the original fracture site, osteotomy
      for the affected tibia was performed with an osteotome after multiple efforts at
      drilling around the nail with the aim of retaining it. Fibula osteotomy was also
      performed at the same level. Two Kirschner wires that created an affected
      rotational angle between the fragments were inserted as a guide for correction.
      The distal locking screws were removed. Correct rotation was regained by matching
      the two wires in a straight line. Finally, the distal locking screws were
      inserted into new holes. The patient obtained bony union and has returned to his
      preinjury activities with no symptoms.

PMID- 30210888
TI  - Pneumomediastinum, Pneumopericardium, and Epidural Pneumatosis following
      Adenotonsillectomy: A Very Rare Complication.
AB  - Adenotonsillectomy is a common surgical otolaryngology procedure that is
      associated with several complications, including hemorrhage, odynophagia, damage
      to teeth, taste disorders, atlantoaxial subluxation, lingual edema, infection,
      and injury of the carotid artery. Pneumomediastinum, pneumopericardium, and
      epidural pneumatosis are an extremely unusual condition in children with
      adenotonsillectomy. Treatment should be conservative in the majority of cases and
      based on benign self-limiting course of these diseases; early recognition can
      prevent further complications. The combination of pneumomediastinum with epidural
      pneumatosis, pneumopericardium, retropharyngeal-prevertebral pneumatosis, axillar
      perihumeral pneumatosis, and subcutaneous emphysema is also a very rare
      condition. We present a unique case with the radiological findings of air in all
      of these areas in a 6-year-old male child with adenotonsillectomy. The case was
      unusual in that the patient developed this complication 3 hours later after
      adenotonsillectomy with severe vomitting. The possible mechanism, the algorithm
      of treatment, and precautions in such cases will be discussed.

PMID- 30210887
TI  - Extensive Bone Lengthening for a Patient with Linear Morphea.
AB  - Localized scleroderma, also known as morphea, is a rare condition characterized
      by progressive sclerosis of the skin and associated atrophy of the underlying
      tissues. The linear type of localized scleroderma is the most frequent form in
      childhood, usually affecting unilateral extremities. Fibrosclerosis of the
      fasciae and muscles can spread across joints and impair the range of motion of
      the joint. Dysplastic and/or atrophic bones of the affected lower extremity can
      lead to clinically significant leg length discrepancy (LLD). Limb reconstruction
      surgery has rarely been indicated for LLD in patients with linear morphea. We
      report on a case of extensive bone lengthening for appreciable LLD in a pediatric
      patient with linear morphea. A Japanese girl with linear morphea underwent staged
      simultaneous lengthening of the femur and tibia twice at seven and eleven years
      of age using a unilateral external fixator. A healing index exceeded 100 days/cm
      except for the first femoral lengthening that was complicated by regenerate
      fracture. At the final follow-up, LLD of 38 mm remained, but she could walk
      independently without a brace or a crutch. Due to soft tissue tightness and poor
      regenerative ability in the affected limb, cautions should be taken to prevent
      regenerate fracture and/or malalignment of the limb.

PMID- 30210889
TI  - A 27-Month-Old Boy with Polyuria and Polydipsia.
AB  - Psychogenic polydipsia is a well-described phenomenon in those with a diagnosed
      psychiatric disorder such as schizophrenia and anxiety disorders. Primary
      polydipsia is differentiated from psychogenic polydipsia by the lack of a clear
      psychotic disturbance. We present a case of a 27-month-old boy who presented with
      polyuria and polydipsia. Laboratory studies, imaging, and an observed water
      deprivation test were consistent with primary polydipsia. Polydipsia resolved
      after family limited his fluid intake and began replacing water drinking with
      other transition objects and behaviors for self-soothing. This case highlights
      the importance of water deprivation testing to differentiate between causes of
      polyuria, thereby avoiding misdiagnosis and iatrogenic hyponatremia. Secondly,
      primary polydipsia can result during the normal stages of child development
      without overt psychiatric disturbances.

PMID- 30210890
TI  - Unsuspected Cause of Respiratory Distress: Unrecognized Esophageal Foreign Body.
AB  - Summary: Foreign bodies in esophagus are avoidable accidents that occur most
      often in children younger than 3 years. The most common presenting symptoms are
      dysphagia, drooling, and vomiting. Revelation by respiratory distress is a rare
      and unusual condition. Objective: We describe and discuss the case of an
      esophageal foreign body, in which the patient presented with respiratory
      distress. Case report: A two-year-old child was admitted to the emergency
      department for acute respiratory distress. He had no history of choking episodes
      or dysphagia. Nevertheless, he was brought by his parents several times for a
      persistent cough and wheezing that was treated as asthma for a month. Pulmonary
      examination had revealed polypnea, suprasternal recession, scattered snoring, and
      diffuse wheeze. As part of his assessment, a chest X-ray was demanded. It had
      shown, as unexpected, a nonmetallic foreign body in the upper thoracic esophagus.
      A clothing button was removed by hypopharyngoscopy under sedation without any
      incident. Subsequent follow-up had not shown any complications related to this
      episode. Conclusion: Large esophageal foreign bodies can impinge on the trachea
      causing upper respiratory tract signs. We alert clinicians on variation in the
      presentation of foreign body ingestion, and we emphasize the importance of an
      early diagnosis and management.

PMID- 30210891
TI  - Asymmetric Omphalopagus in a Triplet after In Vitro Fertilization: A Rare Case of
      Conjoined Twinning.
AB  - Introduction: Asymmetric omphalopagus is a rare situation of conjoined twinning,
      in which a grossly defective twin is attached to the thorax and upper abdomen of
      the main twin. We describe a case of an asymmetric omphalopagus accompanied by a
      normal triplet after assisted reproductive technology (ART) and tried to further
      characterize the all aspects of the conjoined twins. Case Presentation:
      Perioperative diagnostic imaging was carried out followed by an autopsy to
      evaluate all aspects of the parasite accompanied by histological,
      immunohistochemical, and molecular biological evaluation. The parasite had well
      developed lower extremities as well as upper extremities with a cleft hand
      syndrome. The sex was nondeterminable, but DNA fingerprinting revealed that both
      parasite and autosite are monozygotic, so are females. There was no sign of any
      axial skeleton or central nervous system. We found a rudimentary rectum with a
      nonpervious anus, a kidney, ureter, urinary bladder, and a blind-ending urethra.
      The blood supply of the parasite was connected to the vessel system of the
      autosite. Conclusions: To our knowledge, only two cases of parasitic omphalopagus
      after ART have been described to date. Altogether, 52 cases have been reported,
      and in most of them, the parasites were successfully separated.

PMID- 30210892
TI  - Recurrent Acute Neurogenic Pulmonary Edema after Uncontrolled Seizures.
AB  - Acute pulmonary edema following significant injury to the central nervous system
      is known as neurogenic pulmonary edema (NPE). Commonly seen after significant
      neurological trauma, NPE has also been described after seizure. While many
      pathogenic theories have been proposed, the exact mechanism remains unclear. We
      present a 31-year-old man who developed recurrent acute NPE on two consecutive
      admissions after experiencing witnessed generalized tonic-clonic (GTC) seizures.
      Chest radiographs obtained after seizure during both admissions showed bilateral
      infiltrates which rapidly resolved within 24 hours. He required intubation on
      each occasion, was placed on lung protective ventilation, and was successfully
      extubated within 72 hours. There was no identified source of infection, and no
      cardiac pathology was thought to be contributory.

PMID- 30210893
TI  - Nodular Pulmonary Amyloidosis: A Manifestation of Sjogren's Syndrome.
AB  - Case Description: A 72-year-old woman with primary Sjogren Syndrome (SS) was
      diagnosed during an inpatient hospital stay with dry symptoms. The patient had
      respiratory and constitutional symptoms, requiring a pulmonary imaging evaluation
      by high-resolution computed tomography (HRCT) of the thorax. Clinical Findings:
      Multiple cavitary pulmonary nodules, halo sign, and focal areas of ground-glass
      opacity with predominance in both bases were found in the images. Complementary
      studies were done where a neoplastic focus was ruled out. The diagnosis of
      nodular pulmonary amyloidosis was confirmed with a pulmonary biopsy performed by
      videothoracoscopy for histopathological study, which reported the formation of
      nodules in the parenchyma with amyloid deposits and positive immunohistochemical
      markers for CD3, CD20, and CD38 lymphocytic infiltration. Treatment and Outcome:
      Initial inpatient management with intravenous cyclophosphamide and
      methylprednisolone was given. Subsequent outpatient management was given with
      high dose glucocorticoids. Clinical Relevance: We presented a case of nodular
      pulmonary amyloidosis in a female patient with primary SS, which is a rare
      pulmonary manifestation of this syndrome.

PMID- 30210894
TI  - A Rare Case of Cyclical Hemothorax: Thoracic Endometriosis Syndrome.
AB  - Endometriosis is a common condition in which endometrial cells and stroma are
      deposited in extrauterine sites. Its prevalence has been estimated to be 10% of
      reproductive age females. It is commonly found in the pelvis; however, it may be
      found in the abdomen, thorax, brain, or skin. Thoracic involvement is a
      relatively rare presentation of this common disease. Thoracic endometriosis
      commonly presents as pneumothorax in 73% of patients. A rarer presentation of
      thoracic endometriosis is hemothorax (<14%) or hemoptysis (7%). Thoracic
      endometriosis is an uncommon cause of a pleural effusion. We present a case of 28
      year-old African American female with no other medical conditions. She presented
      to the hospital with worsening right-sided pleuritic chest pain, dyspnea, and
      menorrhagia. She had been complaining of pleuritic chest pain for 5 years, the
      onset of which corresponds to the start of her menstrual cycle and is relieved
      with cessation of menses. Initial laboratory studies revealed a severe microcytic
      anemia with normal coagulation profile. Chest X-ray showed small right pleural
      effusion and suspicious for airspace disease. A computed tomography (CT) of chest
      was ordered for further clarification and identified large right pleural
      effusion. CT-guided thoracentesis removed 500 ml of serosanguinous fluid
      consisting of blood elements. There can be multiple sites involved with
      endometriosis and can present with wide range of symptoms that occur periodically
      with menses in young woman. The history and pleural fluid findings of this case
      are suggestive of Thoracic Endometriosis Syndrome. The diagnosis of this is often
      missed or delayed by clinicians, which can result in recurrent hospitalization
      and other complications. As internists we should be suspicious of atypical
      presentations of endometriosis and treat them early before complications develop.
      This case also highlights the importance of suspecting atypical etiologies for
      pleural effusion.

PMID- 30210895
TI  - Direct Intrahepatic Portosystemic Shunt in Budd-Chiari Syndrome: A Case Report
      and Review of the Literature.
AB  - Transjugular intrahepatic portosystemic shunt (TIPS) is an alternative
      interventional procedure used to manage refractory Budd-Chiari syndrome (BCS)
      when conservative medical therapy has failed. However, TIPS is not always
      technically successful because of hepatic vein thrombosis and inability to
      catheterize the hepatic veins. In these situations, direct intrahepatic
      portosystemic shunt (DIPS) with access to the portal vein from the IVC has been
      shown to be a viable alternative that may ameliorate portal hypertension in these
      patients. Typically, DIPS involves the use of transabdominal ultrasound to target
      the portal vein. Herein a case in which a 39-year-old female underwent DIPS
      without the use of ultrasound guidance is presented. Instead, a hepatic venogram
      generated using collateral circulation was used to opacify and guide access to
      the portal vein.

PMID- 30210896
TI  - Immunoglobulin G4 Sclerosing Cholangitis: An Unusual Cause of Obstructive
      Jaundice-Case Report and Literature Review.
AB  - IgG4-related sclerosing cholangitis (IgG4-SC) is one of the most common extra
      pancreatic manifestation of IgG4-related disease (IgG4-RD) and is clinically
      distinct from primary sclerosing cholangitis (PSC). IgG4-RD is an increasingly
      recognized immune-mediated fibroinflammatory systemic disease, mostly affecting
      middle-aged and older male populations that can affect multiple organs. The
      presence of extra-biliary clinical manifestations of IgG4-RD, such as parotid and
      lacrimal swelling, lymphadenopathy, autoimmune pancreatitis, and retroperitoneal
      fibrosis, if present could provide important clues to diagnosis. High serum IgG4
      levels, characteristic radiological (e.g., sausage-shaped pancreas or
      periaortitis) or biopsy findings (high percentage of IgG4+ plasma cells,
      lymphoplasmacytic infiltrate, storiform fibrosis, or obliterative phlebitis) in
      the setting of these features is diagnostic of this disease process. However,
      isolated IgG4-SC might be a diagnostic challenge, and the distinction is
      important as management of this disorder is vastly different from other causes of
      cholangitis such as PSC. Systemic corticosteroid therapy is the mainstay of
      therapy.

PMID- 30210897
TI  - More than Just Story Telling: A Review of Biodiversity Conservation and
      Utilisation from Precolonial to Postcolonial Zimbabwe.
AB  - Access to natural resources has changed over the years in Zimbabwe. At least
      three broad periods of biodiversity conservation, utilisation, and access can be
      identified in the country, namely, the precolonial, colonial, and
      postindependence periods. This paper reviews the relationships between human
      livelihoods and biodiversity conservation in the rural areas of Zimbabwe during
      these periods and is informed by an extensive review of the relevant literature.
      A combination of historical narrative, thematic, and content analysis was used in
      analysing the various documents into meaningful information addressing the
      objective of the study. Traditional societies in precolonial Zimbabwe had access
      to abundant natural resources. However, access to these resources was not
      uncontrolled, but was limited by traditional beliefs, taboos, and customs
      enforced through community leadership structures. The advent of colonialism in
      the late 19th century dispossessed indigenous African communities of natural
      resources through command-type conservation legislation. At independence in 1980,
      the new majority government sought to redress the natural resource ownership
      imbalances created during colonialism, culminating in some significant measure of
      devolution in natural resource management to local communities in the late 1980s,
      though such devolution has been criticised for being incomplete. An accelerated
      land reform exercise since the year 2000 has adversely affected biodiversity
      conservation activities in the country, including the conservation-related
      livelihood benefits derived from protected areas. The review paper highlights the
      need for a more complete devolution of natural resource ownership and management
      down to the grassroots levels in the communal areas, if social and ecological
      sustainability is to be fully realised in these areas. On the other hand, the
      disruption of conservation activities in the country due to the ill-planned
      accelerated land reform exercise that has demarcated land for arable farming in
      some of the protected areas should be held in check as a matter of urgency.

PMID- 30210898
TI  - Aberrant activation of latent transforming growth factor-beta initiates the onset
      of temporomandibular joint osteoarthritis.
AB  - There is currently no effective medical treatment for temporomandibular joint
      osteoarthritis (TMJ-OA) due to a limited understanding of its pathogenesis. This
      study was undertaken to investigate the key role of transforming growth factor
      beta (TGF-beta) signalling in the cartilage and subchondral bone of the TMJ using
      a temporomandibular joint disorder (TMD) rat model, an ageing mouse model and a
      Camurati-Engelmann disease (CED) mouse model. In the three animal models, the
      subchondral bone phenotypes in the mandibular condyles were evaluated by uCT, and
      changes in TMJ condyles were examined by TRAP staining and immunohistochemical
      analysis of Osterix and p-Smad2/3. Condyle degradation was confirmed by Safranin
      O staining, the Mankin and OARSI scoring systems and type X collagen (Col X), p
      Smad2/3a and Osterix immunohistochemical analyses. We found apparent histological
      phenotypes of TMJ-OA in the TMD, ageing and CED animal models, with abnormal
      activation of TGF-beta signalling in the condylar cartilage and subchondral bone.
      Moreover, inhibition of TGF-beta receptor I attenuated TMJ-OA progression in the
      TMD models. Therefore, aberrant activation of TGF-beta signalling could be a key
      player in TMJ-OA development.

PMID- 30210899
TI  - Alpl prevents bone ageing sensitivity by specifically regulating senescence and
      differentiation in mesenchymal stem cells.
AB  - Mutations in the liver/bone/kidney alkaline phosphatase (Alpl) gene cause
      hypophosphatasia (HPP) and early-onset bone dysplasia, suggesting that this gene
      is a key factor in human bone development. However, how and where Alpl acts in
      bone ageing is largely unknown. Here, we determined that ablation of Alpl induces
      prototypical premature bone ageing characteristics, including bone mass loss and
      marrow fat gain coupled with elevated expression of p16INK4A (p16) and p53 due to
      senescence and impaired differentiation in mesenchymal stem cells (MSCs).
      Mechanistically, Alpl deficiency in MSCs enhances ATP release and reduces ATP
      hydrolysis. Then, the excessive extracellular ATP is, in turn, internalized by
      MSCs and causes an elevation in the intracellular ATP level, which consequently
      inactivates the AMPKalpha pathway and contributes to the cell fate switch of
      MSCs. Reactivating AMPKalpha by metformin treatment successfully prevents
      premature bone ageing in Alpl+/- mice by improving the function of endogenous
      MSCs. These results identify a previously unknown role of Alpl in the regulation
      of ATP-mediated AMPKalpha alterations that maintain MSC stemness and prevent bone
      ageing and show that metformin offers a potential therapeutic option.

PMID- 30210901
TI  - Adhesion sutures for seroma reduction in cranial reconstructions with polymethyl
      methacrylate prosthesis in patients undergoing decompressive craniectomy: A
      clinical trial.
AB  - Background: Cranial reconstruction with polymethyl methacrylate (PMMA) prosthesis
      is used for calvarial defects secondary to decompressive craniectomies. Seroma is
      one of the most frequent complications of this procedure and can lead to the
      dehiscence, extrusion, infection, and loss of the prosthesis. The objective of
      the study is to analyze the effectiveness of the tacking sutures between the
      prosthesis and the scalp flap in reducing the seroma. Methods: This is a
      prospective study with 63 patients submitted to cranioplasty between 2014 and
      2017 for defects resulting from decompressive craniectomies. All patients were
      followed up postoperatively for at least 3 months and the diagnosis of seroma was
      made clinically. In the first 22 patients, the conventional technique was applied
      and, in the following 41, the technique with tacking sutures was used. The
      incidence of seroma was collected for both groups. Results: The overall incidence
      of seroma was 65.1%. Compared to the conventional technique, the use of tacking
      sutures was associated with a statistically significant reduction in the
      incidence of seroma from 90.9% to 51.2% (P = 0.002). Conclusion: The use of the
      tacking sutures in cranioplasties with PMMA prosthesis reduced the incidence of
      seroma postoperatively.

PMID- 30210903
TI  - One burr-hole craniotomy: Suboccipital midline approach to the fourth ventricle
      in Helsinki neurosurgery.
AB  - Background: In this video-abstract, we present one burr-hole craniotomy for the
      standard suboccipital midline approach developed in Helsinki neurosurgery for the
      microsurgical management of forth ventricle lesions, distal posterior inferior
      cerebellar artery aneurysms, and tumoral and vascular lesions of the vermis,
      cisterna magna region, and posterior brainstem as well. Case Description: We
      prefer to position the patient in sitting praying position. A midline straight
      single-layer incision starts on the inion and extends caudally toward the level
      of C2. The muscles are divided with diathermia along the occipital bone. Three
      curved retractors, two upward and one downward, provide a wide clean space for
      the craniotomy. Finger palpation and blunt dissection with cottonoids balls
      provide identification of the foramen magnum and the spinous process of C1. A
      burr-hole is made 1 cm lateral and below the level of the transverse sinus. After
      the detachment of the dura with a curved angled dissector, two cuts from both
      sites of the burr-hole are made with the craniotome. In case of an adherent dura
      particularly present in elderly patients, a long blunt flexible dissector
      (yasargil dissector) is used for the detachment of the bone from the dura. A
      craniotomy around the midline overlying the occipital sinus and the falx
      cerebelli is performed to expose medial aspects of cerebellar tonsils, the
      medulla oblongata, and the occipital sinus. Special care should be taken to avoid
      damaging the vertebral artery and the epidural sinuses running at the foramen
      magnum. A few drill holes are made for tack-up sutures. After a craniocervical
      based opening of the dura, the fourth ventricle is accessed directly by telovelar
      route. Conclusion: The described one burr-hole craniotomy may represent the more
      efficient manner for performing the suboccipital midline approach to the fourth
      ventricle. Videolink: http://surgicalneurologyint.com/videogallery/suboccipital
      midline-approach/.

PMID- 30210900
TI  - Mandible exosomal ssc-mir-133b regulates tooth development in miniature swine via
      endogenous apoptosis.
AB  - Signal transduction between different organs is crucial in the normal development
      of the human body. As an important medium for signal communication, exosomes can
      transfer important information, such as microRNAs (miRNAs), from donors to
      receptors. MiRNAs are known to fine-tune a variety of biological processes,
      including maxillofacial development; however, the underlying mechanism remains
      largely unknown. In the present study, transient apoptosis was found to be due to
      the expression of a miniature swine maxillofacial-specific miRNA, ssc-mir-133b.
      Upregulation of ssc-mir-133b resulted in robust apoptosis in primary dental
      mesenchymal cells in the maxillofacial region. Cell leukemia myeloid 1 (Mcl-1)
      was verified as the functional target, which triggered further downstream
      activation of endogenous mitochondria-related apoptotic processes during tooth
      development. More importantly, mandible exosomes were responsible for the initial
      apoptosis signal. An animal study demonstrated that ectopic expression of ssc-mir
      133b resulted in failed tooth formation after 12 weeks of subcutaneous
      transplantation in nude mice. The tooth germ developed abnormally without the
      indispensable exosomal signals from the mandible.

PMID- 30210902
TI  - Epidural cerebrospinal fluid collection following lumbar puncture in an adult
      patient: A case report and literature review.
AB  - Background: Cerebrospinal fluid (CSF) leakage into the epidural space following
      lumbar puncture (LP) has been documented in pediatric patients, but there have
      been no reported cases in adults. Case Description: We report an epidural CSF
      leak in an adult who presented with back pain, positional headache, urinary
      retention, and constipation following an LP performed as a part of a research
      study. The patient's magnetic resonance (MR) scan showed an extensive epidural
      CSF collection. Following placement in a recumbent position for 72 h, the
      collection fully resolved along with his neurological complaints. Conclusion:
      Symptomatic epidural CSF collections rarely occur in adults following LPs.
      Nevertheless, the management remains the same as for pediatric patients; bed rest
      for 72 h results typically in full resolution of symptoms/signs and regression of
      the collection on MR studies.

PMID- 30210904
TI  - External cortical landmarks for localization of the hippocampus: Application for
      temporal lobectomy and amygdalohippocampectomy.
AB  - Background: Accessing the hippocampus for amygdalohippocampectomy and minimally
      invasive procedures, such as depth electrode placement, require an accurate
      knowledge regarding the location of the hippocampus. Methods: The authors removed
      10 human cadaveric brains from the cranium and observed the relationships between
      the lateral temporal neocortex and the underlying hippocampus. They then measured
      the distance between the hippocampus and superficial landmarks. The authors also
      validated their study using magnetic resonance imaging (MRI) scans of 10 patients
      suffering from medial temporal lobe sclerosis where the distance from the
      hippocampal head to the anterior temporal tip was measured. Results: In general,
      the length of the hippocampus was along the inferior temporal sulcus and inferior
      aspect of the middle temporal gyrus. Although the hippocampus tended to be more
      superiorly located in female specimens and on the left side, this did not reach
      statistical significance. The length of the hippocampus tended to be shorter in
      females, but this too failed to reach statistical significance. The mean distance
      from the anterior temporal tip to the hippocampal head was identical in the
      cadavers and MRIs of patients with medial temporal lobe sclerosis. Conclusions:
      Additional landmarks for localizing the underlying hippocampus may be helpful in
      temporal lobe surgery. Based on this study, there are relatively constant
      anatomical landmarks between the hippocampus and overlying temporal cortex. Such
      landmarks may be used in localizing the hippocampus during
      amygdalohippocampectomy and depth electrode implantation in verifying the
      accuracy of image-guided methods and as adjuvant methodologies when these latter
      technologies are not used or are unavailable.

PMID- 30210906
TI  - Progressive edematous lesions in subacute phase after neuroendovascular therapy.
AB  - Background: The appearance of edematous lesions in the subacute phase is a rare
      complication following neuroendovascular therapy. Effective management of these
      lesions remains unclear. In this report, a case with progressive edematous
      lesions in the subacute phase after neuroendovascular therapy was described, and
      the clinical features and therapeutic strategies were discussed. Case
      Description: A 54-year-old female with a large, right cavernous internal carotid
      artery aneurysm was treated with a flow diverter. Left hemiparesis developed 15
      days after the procedure, and multiple edematous lesions in areas of prior
      catheter procedures were revealed on radiological findings. Steroid pulse therapy
      was employed, and the lesions were gradually reduced without any additional
      neurological deficits. No recurrence was recognized in the follow-up study.
      Conclusion: In some reports, pathological findings indicate that these lesions
      result from the presence of foreign bodies, and emboli could be caused by cotton
      fibers or hydrophilic polymers used as surface coatings on endovascular
      catheters. In this case, the edematous lesions were most likely caused by
      hydrophilic polymer emboli. Steroid pulse therapy had a beneficial effect on the
      lesions. It is important to effectively manage prescribed periods after the
      procedure to avoid such a rare complication.

PMID- 30210905
TI  - Morphometrics predicts overall survival in patients with multiple myeloma spine
      metastasis: A retrospective cohort study.
AB  - Background: Treatment strategies for spinal metastases for myeloma range from
      conservative measures (radiation and chemotherapy) to invasive (surgical).
      Identifying better predictors of overall survival (OS) would help in surgical
      decision making. Analytic morphometrics has been shown to predict survival in
      oncologic patients, and our study evaluates whether morphometrics is predictive
      of survival in patients with multiple myeloma (MM) spinal metastases. Methods:
      For this observational retrospective cohort study, we identified 46 patients with
      MM spinal metastases who had undergone stereotactic body radiation therapy. OS
      was the primary outcome measure. Morphometric analysis of the psoas muscle was
      performed using computed tomography scans of the lumbar spine. Results: OS was
      statistically correlated with age (P = 0.025), tumor burden (P = 0.023), and
      number of levels radiated (P = 0.029), but not with gender. Patients in the
      lowest tertile of average psoas size had significantly shorter survival compared
      to the highest tertile, hazard ratio (HZ) 6.87 (95% CI = 1.65-28.5, P = 0.008).
      When calculating the psoas size to vertebral body ratio and correlating this
      measure to OS, the lowest tertile again had significantly shorter OS compared to
      the highest tertile, HZ 6.87 (95% CI = 1.57-29.89, P = 0.010); the middle tertile
      also showed significantly shorter OS compared to the highest tertile, HZ 5.07
      (95% CI = 1.34-19.10, P = 0.016). Kaplan-Meier survival curves were used to
      visually illustrate the differences in survival between different tertiles (Log
      rank test P = 0.006). Conclusions: Morphometric analysis successfully predicts
      long-term survival in patients with MM. More research is needed to validate these
      results and to see if these methodologies can be applied to other cancer
      histologies.

PMID- 30210907
TI  - Cavernoma of the cauda equina.
AB  - Background: Cavernomas are benign malformations of the vasculature. In the
      central nervous system, they are mostly located supratentorially. However, in
      adults, cavernomas also comprise about 3% of all subdural spinal cord tumors.
      Notably, cavernomas of the cauda equina are extremely rare, with only 23 cases
      reported in the literature. Here, we report the 24th case involving a 77-year-old
      male. Case Description: A 77-year-old male presented with low back pain for 3
      years duration. His history included prostate cancer, skin melanoma, and a sick
      sinus syndrome requiring a pacemaker. An enhanced computed tomography of the
      lumbar spine showed an inhomogeneously enhanced, intramedullary mass, located at
      the L3 level. The patient underwent an L3 hemilaminectomy with gross total
      excision of the lesion. Macroscopically, the tumor was mulberry-shaped and well
      demarcated. However, it was strongly adherent to a nerve root of the cauda equina
      which required resection. The histologic examination was consistent with a
      cavernoma. The patient subsequently fully recovered without a focal neurological
      deficit. Conclusions: Cavernomas of the cauda equina are extramedullary, arise on
      the inner aspect of the dura, and may be tightly adhered to the nerve roots. To
      attain gross total excision, the involved nerve may have to be sacrificed; in
      some cases, this may result in a permanent neurological deficit. Of interest,
      half of the cauda equina lesions were previously found in patients who had prior
      radiotherapy; this was not the case in this patient.

PMID- 30210908
TI  - Engineering exosomes: a new direction for anticancer treatment.
AB  - Currently, lacks of specificity and effectiveness remain the main drawbacks of
      clinical cancer treatment. Despite therapeutic advances in recent decades,
      clinical outcomes remain poor. Exosomes are nanosized particles with great
      potential for enhancing anticancer responses and targeted drug delivery. Exosomes
      modified through genetic or nongenetic methods can augment the cytotoxicity and
      targeting ability of therapeutic agents, thus improving their efficacy in killing
      cancer cells. In this review, we summarize recent research on engineering
      exosomes-based cancer therapy and discuss exosomes derived from tumors,
      mesenchymal stem cells, dendritic cells, HEK293T cells, macrophages, milk, and
      other donor cells. The antitumor effects of engineered-exosomes are highlighted
      and the potential adverse effects are considered. A comprehensive understanding
      of exosomes modification may provide a novel strategy for cancer therapy.

PMID- 30210909
TI  - Multifaceted regulation and functions of replication factor C family in human
      cancers.
AB  - Replication factor C (RFC) family is a complex comprised of the RFC1, RFC2, RFC3,
      RFC4, and RFC5 subunits, which acts as a primer recognition factor for DNA
      polymerase. It is reported that RFC, biologically active in various malignant
      tumors, may play an important role in the proliferation, progression, invasion,
      and metastasis of cancer cells. It could act as an oncogene or tumor suppressor
      gene based on the cellular and histological characteristics of the tumor. In this
      review, we summarized the updated researches on the structure, physiological
      function, and expression pattern of RFC in a variety of tumors, the underlying
      mechanisms on carcinogenesis, and the potentials of RFC family members in the
      diagnosis and prognosis prediction.

PMID- 30210912
TI  - A three miRNAs signature for predicting the transformation of oral leukoplakia to
      oral squamous cell carcinoma.
AB  - Oral squamous cell carcinoma (OSCC) remains to be a global health problem.
      However, the underlying molecular mechanisms regulating the oral leukoplakia
      (OLK) to OSCC remain poorly known. MicroRNAs (miRNAs) expression profiles of
      GSE33299 and GSE62809 were downloaded from gene expression omnibus (GEO)
      respectively. R software and bioconductor packages were used to compare and
      identify the differentially expressed miRNAs between OLK tissues and OLK
      transformed OSCC (OLK-OSCC). The target genes of commonly changed miRNAs were
      then subjected to gene ontology (GO) enrichment analysis, pathway analysis and
      miRNA-target genes network analysis. The prediction power of commonly changed
      miRNAs was further tested in an independent cohort. In total, 161 (88 upregulated
      and 73 downregulated) and 68 (19 upregulated and 49 downregulated) markedly
      altered miRNAs were identified from GSE33299 and GSE62809 respectively. The
      downstream targets of these differentially expression miRNAs in the two cohorts
      shared many top enriched GO and KEGG pathways. A set of three miRNAs signature
      including miR-129-5p, miR-296-5p and miR-450b-5p was commonly changed in both
      GSE33299 and GSE62809. Functional analysis revealed that the downstream target
      genes of the miRNA signature were associates with transcriptional regulation,
      estrogen signaling pathway, p53 signaling pathway and RIG-I-like receptor
      signaling pathway. This three-gene signature was further successfully validated
      in another independent cohort. The expression levels of miR-129-5p and miR-296-5p
      were significantly downregulated in OLK-OSCC tissues compared to OLK tissues,
      while miR-450b-5p levels were higher in OLK-OSCC tissues. In addition, this three
      miRNAs signature could discriminate OLK from OLK-OSCC with high accuracy. In
      conclusion, our study has identified a three miRNAs signature that might help
      predict the transformation of OLK to OSCC. Which will provide useful guidance for
      therapeutic applications.

PMID- 30210911
TI  - A novel circular RNA hsa_circ_0020123 exerts oncogenic properties through
      suppression of miR-144 in non-small cell lung cancer.
AB  - Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer-related
      death worldwide, while circulatory. Circular RNAs (circRNAs) are found to play
      important roles in cancer initiation and development. Herein, a novel functional
      circRNA hsa_circ_0020123 had been identified in NSCLC progression in this study,
      and elevated hsa_circ_0020123 expression could be observed in cancer tissues
      compared with that in matched normal lung tissues. Moreover, up-regulation of
      hsa_circ_0020123 was recognized to be closely associated with a poor
      differentiation degree, lymph node metastasis, a high TNM stage and dismal
      prognosis for NSCLC patients. Typically, knockdown of hsa_circ_0020123 could
      inhibit the NSCLC growth and metastasis both in vitro and in vivo, which could be
      reversed by the hsa_circ_0020123 overexpression. Importantly, miR-144 was
      identified as the hsa_circ_0020123-associated miRNA through performing RNA in
      vivo precipitation (RIP) in NSCLC cells using a biotin-labeled hsa_circ_0020123
      probe. Besides, our results suggested that, miR-144 suppression had determined
      the oncogenic properties mediated by hsa_circ_0020123. In addition,
      hsa_circ_0020123 could upregulate ZEB1 and EZH2 through competitively binding
      with miR-144. Finally, the administration of hsa_circ_0020123 siRNA could
      suppress the growth and metastasis in NSCLC-bearing mice in vivo. In conclusion,
      the hsa_circ_0020123-miR-144-ZEB1/EZH2 axis is critical for NSCLC progression,
      which indicates that hsa_circ_0020123 is a potential target for NSCLC treatment.

PMID- 30210914
TI  - The lncKLF6/KLF6 feedback loop regulates the growth of non-small cell lung
      cancer.
AB  - Non-small lung cancer (NSCLC) is one of the most common causes of cancer
      associated death worldwide. Long noncoding RNAs (lncRNAs) regulate cancer
      initiation and progression through different mechanisms. In the present study, we
      characterized a novel lncRNA named lncKLF6, which was upregulated in NSCLC and
      associated with poor clinical outcomes. lncKLF6 inhibited Kruppel-like factor 6
      (KLF6) transcription and then facilitated NSCLC growth. lncKLF6 is associated
      with the epigenetic repressor BMI1 and regulates its stability via recruiting
      deubiquitinase USP22. Moreover, it was revealed that lncKLF6 was a KLF6
      responsive lncRNA, as KLF6 could occupy the lncKLF6 promoter to facilitate its
      transcription. The negative feedback loop of lncKLF6 and KLF6 continuously
      enhanced the oncogenic effects. Thus, our study elucidates the mechanism of
      lncKLF6-mediated growth via suppression of KLF6, which provides the promising
      target for developing new therapeutic strategy in NSCLC.

PMID- 30210913
TI  - GAS5 functions as a ceRNA to regulate hZIP1 expression by sponging miR-223 in
      clear cell renal cell carcinoma.
AB  - Several studies have shown that low expression of hZIP1 is closely associated
      with many human cancers, including clear cell renal cell carcinoma (ccRCC). In
      this study, we aimed to explore the potential mechanism responsible for hZIP1
      silencing and revealed a novel regulatory pathway in the pathogenesis of ccRCC.
      Here, miR-223 was predicted and experimentally validated to be a regulator of
      hZIP1, and its expression was negatively correlated with the mRNA levels of hZIP1
      in primary tumors. Upregulation of hZIP1 inhibited cell proliferation, cell cycle
      progression, and invasion and induced apoptosis, while inhibition of miR-223
      showed the opposite effect on cellular processes. Moreover, GAS5 interacted with
      miR-223 and was markedly downregulated in tumors. Knockdown of GAS5 partially
      reversed the effect of the miR-223 inhibitor on cell proliferation, cell cycle
      distribution, apoptosis and invasion. In addition, GAS5 acted as a molecular
      sponge to positively regulate the mRNA and protein levels of hZIP1 via regulating
      miR-223. The tumorigenicity of ccRCC cells was enhanced by silencing GAS5 but
      diminished by overexpression of hZIP1 in vivo. Clinically, the low expression of
      hZIP1 was significantly correlated with advanced clinical stage and Fuhrman
      stage. Downregulation of GAS5 indicated tumor progression and recurrence and was
      independently associated with disease-free survival of patients. Taken together,
      our results suggest that GAS5 may act as a competing endogenous RNA (ceRNA) to
      regulate hZIP1 by sponging miR-223 in the progression of ccRCC and that targeting
      the GAS5/miR-223/hZIP1 axis may serve as a therapeutic strategy for patients.

PMID- 30210915
TI  - Prognosis of FTC compared to PTC and FVPTC: findings based on SEER database using
      propensity score matching analysis.
AB  - The significance of prognosis of follicular thyroid cancer (FTC) compared to
      other subtypes of thyroid cancer, based on large cohort data has only been
      addressed in a few studies, and the results remain controversial. In this study,
      we investigated the prognosis of FTC compared to papillary thyroid carcinoma
      (PTC) and follicular variant PTC (FVPTC) based on Surveillance, Epidemiology, and
      End Results database (SEER) Program data using propensity score matching. We
      evaluated data from 128,703 patients with thyroid cancer who were included in the
      SEER database between 2004 and 2013. Patient mortality was evaluated using Cox
      proportional hazards regression analyses and Kaplan-Meier analyses with log-rank
      tests. The average prognosis of FTC was poorer than both PTC and FVPTC. The
      multivariate Cox regression analysis revealed that the cancer-specific survival
      rate for FTC was lower than that for PTC and FVPTC without adjusting for risk
      factors. Furthermore, after propensity score matching analysis for relevant
      factors, the cancer-specific mortality rate for FTC was higher than that for PTC
      and FVPTC. These results based on a large population cohort database provide a
      benefit reference for individual and precise treatment and management of patients
      with FTC.

PMID- 30210910
TI  - Genomics of adult and pediatric solid tumors.
AB  - Different types of cancers exhibit disparate spectra of genomic alterations
      (germline and/or somatic). These alterations can include single nucleotide
      variants (SNVs), copy number alterations (CNAs) or structural changes (e.g. gene
      fusions and chromosomal rearrangements). Identification of those genomic
      alterations has provided the opportune element to derive new strategies for
      molecular-based precision medicine of adult and pediatric cancers including risk
      assessment, non-invasive detection, molecular diagnosis and personalized therapy.
      Moreover, it is now becoming clear that the spectra of genomic-based alterations
      and mechanisms in pediatric malignancies are different from those predominantly
      occurring in adult cancer. Adult cancers on average exhibit substantially higher
      mutational burdens compared with the vast majority of childhood tumors.
      Accumulating evidence also suggests that the type of genomic alterations
      frequently encountered in adult cancers is different from those observed in
      pediatric malignancies. In this review, we discuss the state of knowledge on
      adult and pediatric cancer genomes (or "mutatomes"), specifically focusing on
      solid tumors. We present an overview of mutational signatures and processes in
      cancer as well as comprehensively compare and contrast the diverse spectra of
      genomic alterations (somatic and familial) among major adult and pediatric solid
      tumors. The review also discusses the role of genomics in molecular-based
      precision medicine of adult and pediatric solid malignancies as well as
      comprehending resistance mechanisms to various targeted therapies. In addition,
      we present a perspective that discusses upon emerging concepts in cancer genomics
      including intratumoral heterogeneity, the precancer (premalignant) genome as well
      as the interface between the host immune response and tumor genome -
      immunogenomics - as they relate to adult and pediatric tumors.

PMID- 30210916
TI  - Upregulation of C/EBPalpha contributes to colorectal cancer growth, metastasis
      and indicates poor survival outcome.
AB  - The function and clinical implication of transcription factor CCAAT/enhancer
      binding protein alpha (C/EBPalpha) in colorectal cancer (CRC) still remains
      undefined. In fact, C/EBPalpha has long been considered as a tumor suppressor in
      hematopoietic system and also found lowly expressed in numerous solid tumors.
      However, our results here for the first time showed that C/EBPalpha was
      unexpectedly upregulated and was an independent prognostic marker for patients
      with CRC. We therefore aimed to explore the detailed role and mechanisms of
      C/EBPalpha in CRC. Our investigation demonstrated that C/EBPalpha promoted tumor
      growth both in vitro and in vivo. In addition, suppression of C/EBPalpha
      inhibited cell proliferation by inducing G1 phase arrest and inducing apoptosis.
      Also, C/EBPalpha enhances CRC cells migration and invasion in vitro as well as
      metastasis in vivo through regulating EMT. Mechanistically, C/EBPalpha exerts its
      oncogenic role by targeting c-Myc/cyclin D1 mediated by beta-catenin involved
      pathway and we provide evidence indicating that cytoplasmic exclusion of
      C/EBPalpha might contribute to its oncogenic function in tumor progression. In
      conclusion, C/EBPalpha acts as an oncogene in CRC and could be a potential
      biomarker of colon carcinogenesis.

PMID- 30210918
TI  - Long noncoding RNA TOB1-AS1, an epigenetically silenced gene, functioned as a
      novel tumor suppressor by sponging miR-27b in cervical cancer.
AB  - Cervical cancer is one of the most common cancers in females, accounting for a
      majority of cancer-related deaths in worldwide. Long non-coding RNAs (lncRNAs)
      have been identified as critical regulators in many tumor-related biological
      processes. Thus, investigation into the function and mechanism of lncRNAs in the
      development of cervical cancer is very necessary. In this study, we found that
      the expression of TOB1-AS1 was significantly decreased in cervical cancer tissues
      compared with the adjacent normal tissues. The methylation status of TOB1-AS1
      related CpG island was analyzed using methylation specific PCR and bisulfite
      sequencing analysis, revealing that the aberrant hypermethylation of TOB1-AS1
      related CpG island was frequently observed in primary tumors and cervical cancer
      cells. The expression of TOB1-AS1 in cervical cancer cells could be reversed by
      demethylation agent treatment. Functionally, overexpression of TOB1-AS1
      significantly inhibited cell proliferation, cell cycle progression, invasion and
      induced apoptosis, while knockdown of TOB1-AS1 exhibited the opposite effect.
      Furthermore, it was determined that TOB1-AS1 was able to bind and degrade the
      expression of miR-27b. Upregulation of miR-27b promoted cell growth, cell cycle
      transition from G1 phase to S phase, and invasion and reduced apoptosis,
      phenomenon could be reversed by TOB1-AS1. Inhibition of miR-27b attenuated the
      promotive effect of si-TOB1-AS1 on cellular processes. Upregulation of TOB1-AS1
      also suppressed tumor growth in vivo. Clinically, methylation of TOB1-AS1 and low
      expression of TOB1-AS1 was significantly correlated with tumor stage and tumor
      size, respectively. Univariate and multivariate analyses confirmed that low level
      of TOB1-AS1 was an independent risk factor for death. In conclusion, we suggested
      that the epigenetically silenced TOB1-AS1 was unable to restrain miR-27b, which
      contributed to cervical cancer progression.

PMID- 30210917
TI  - Axl inhibitor R428 induces apoptosis of cancer cells by blocking lysosomal
      acidification and recycling independent of Axl inhibition.
AB  - R428 (BGB324) is an anti-cancer drug candidate under clinical investigation. It
      inhibits the receptor tyrosine kinase Axl and induces apoptosis of many types of
      cancer cells, but the relationship between the two has not been well established.
      We investigated the molecular mechanisms of the R428-induced apoptosis and found
      that R428 induced extensive cytoplasmic vacuolization and caspase activation,
      independent of its inhibitory effects on Axl. Further analyses revealed that R428
      blocked lysosomal acidification and recycling, accumulated autophagosomes and
      lysosomes, and induced cell apoptosis. Inhibition of autophagy by autophagy
      inhibitors or autophagic gene-knockout alleviated the R428-induced vacuoles
      formation and cell apoptosis. Our study uncovered a novel function and mechanism
      of R428 in addition to its ability to inhibit Axl. These data will help to better
      direct the application of R428 as an anti-cancer reagent. It also adds new
      knowledge to understand the regulation of autophagy and apoptosis.

PMID- 30210919
TI  - An anti-ASCT2 monoclonal antibody suppresses gastric cancer growth by inducing
      oxidative stress and antibody dependent cellular toxicity in preclinical models.
AB  - Glutamine is a major nutrient for cancer cells during rapid proliferation.
      Alanine-serine-cysteine (ASC) transporter 2 (ASCT2; SLC1A5) mediates glutamine
      uptake in a variety of cancer cells. We previously reported that KM8094, a novel
      anti-ASCT2 humanized monoclonal antibody, possesses anti-tumor efficacy in
      gastric cancer patient-derived xenografts. The aim of this study was to
      investigate the molecular mechanism underlying the effect of KM8094 and to
      further substantiate the preclinical feasibility of using KM8094 as a potential
      therapeutic agent against gastric cancer. First, ASCT2 was found to be highly
      expressed in cancer tissues derived from gastric cancer patients by an
      immunohistochemical analysis. Next, we performed in vitro studies using multiple
      gastric cancer cell lines and observed that several gastric cancer cells
      expressing ASCT2 showed glutamine-dependent cell growth, which was repressed by
      KM8094. We found that KM8094 inhibited the glutamine uptake, leading to the
      reduction of glutathione (GSH) level and the elevation of oxidative stress.
      KM8094 suppressed the cell cycle progression and increased the apoptosis.
      Furthermore, KM8094 exerted antibody dependent cellular cytotoxicity (ADCC)
      against human gastric cancer cells in vitro. Finally, in vivo studies revealed
      that KM8094 suppressed tumor growth in several gastric cancer xenografts. This
      effect was enhanced by docetaxel, one of the agents commonly used in gastric
      cancer therapy. Thus, our findings suggest that KM8094 is a potential new
      therapeutic agent for gastric cancer expressing ASCT2, which blocks the cellular
      glutamine metabolism and possesses ADCC activity.

PMID- 30210920
TI  - Oncolytic Newcastle disease virus induces autophagy-dependent immunogenic cell
      death in lung cancer cells.
AB  - In addition to direct oncolysis, oncolytic viruses trigger immunogenic cell death
      (ICD) and primes antitumor immunity. We have previously shown that oncolytic
      Newcastle disease virus (NDV), strain FMW (NDV/FMW), induces apoptosis and/or
      autophagy in cancer cells. In this study, we investigated whether oncolytic NDV
      can induce ICD in lung cancer cells and whether apoptosis or autophagy plays a
      role in NDV-triggered ICD. To this end, we examined cell surface expression of
      calreticulin (CRT) on NDV-infected lung cancer cells and measured ICD
      determinants, high mobility group box 1 (HMGB1), heat shock protein 70/90
      (HSP70/90) and ATP in supernatants following viral infection. Flow cytometric
      analysis using anti-CRT antibody and PI staining of NDV-infected lung cancer
      cells showed an increase in the number of viable (propidium iodide-negative)
      cells, suggesting the induction of CRT exposure upon NDV infection. In addition,
      confocal and immunoblot analysis using anti-CRT antibody showed that an enhanced
      accumulation of CRT on the cell surface of NDV-infected cells, indicating the
      translocation of CRT to the cell membrane upon NDV infection. We further
      demonstrated that NDV infection induced the release of secreted HMGB1 and
      HSP70/90 by examining the concentrated supernatants of NDV-infected cells.
      Furthermore, pre-treatment with either the pan-caspase inhibitor z-VAD-FMK or the
      necrosis inhibitor Necrostain-1, had no impact on NDV-induced release of ICD
      determinants in lung cancer cells. Rather, depletion of autophagy-related genes
      in lung cancer cells significantly inhibited the induction of ICD determinants by
      NDV. Of translational importance, in a lung cancer xenograft model, treatment of
      mice with supernatants from NDV-infected cells significantly inhibited tumour
      growth. Together, these results indicate that oncolytic NDV is a potent ICD
      inducer and that autophagy contributes to NDV-mediated induction of ICD in lung
      cancer cells.

PMID- 30210921
TI  - Baicalein suppress EMT of breast cancer by mediating tumor-associated macrophages
      polarization.
AB  - Tumor associated macrophages (TAMs) are the main infiltrating component in the
      tumor microenvironment and play an important role in cancer progression.
      Baicalein has a wide range of pharmacological properties. This study explores the
      potential effect of baicalein on macrophages polarization and epithelial
      mesenchymal transition (EMT) of breast cancer. Co-culture system was established
      to evaluate the interaction between TAMs and breast cancer cells. Then the role
      of baicalein in modulating TAMs function was assessed. Finally, breast cancer
      mouse model was established to study the underlying mechanism. In vitro
      experiments showed that co-culture with M2 macrophages significantly enhanced EMT
      of both MDA-MB-231 and MCF-7 breast cancer cells. Baicalein could regulate
      polarization of M2 and attenuate TGF-beta1 secretion. In vivo experiments showed
      that compared with the MDA-MB-231 + M2 group, tumor growth and metastasis of
      baicalein + MDA-MB-231 + M2 group was significantly inhibited, with smaller tumor
      size and decreased lung metastasis lesions. Our findings suggest that the
      regulation of TAMs may be a novel mechanism underlying the anti-tumor effects of
      baicalein in breast cancer.

PMID- 30210922
TI  - Pharmacologic characterization of CT-711, a novel dual inhibitor of ALK and c
      Met.
AB  - Anaplastic lymphoma kinase (ALK) is a validated molecular target for patients
      harboring ALK rearrangement, which triggers the development of ALK inhibitors.
      However, the activation of mesenchymal-epithelial transition factor (c-Met) has
      emerged as a common cause of acquired resistance induced by selective ALK
      inhibitors. Herein, we report the first preclinical characterization of CT-711, a
      novel dual inhibitor of ALK and c-Met. CT-711 demonstrates potent inhibitory
      activity against ALK kinase activity. Moreover, CT-711 profoundly inhibits ALK
      signal transduction and thereby induces G1 phase arrest and apoptosis, and
      results in remarkable anti-proliferative activity against ALK-driven cancer
      cells. Furthermore, CT-711 effectively inhibits c-Met kinase activity and
      potently overcomes the resistance mediated by c-Met activation. When orally
      administered to nude mice bearing xenografts, CT-711 exhibits favorable
      pharmacokinetic properties and robust antitumor activity. It is noteworthy that
      CT-711 is superior to crizotinib, the first-in-class ALK inhibitor, in the
      treatment of ALK-driven cancers in various models. The results of the current
      study provide a solid foundation for the clinical investigation of CT-711 in
      patients with tumors harboring ALK rearrangement.

PMID- 30210923
TI  - ONC201 demonstrates anti-tumorigenic and anti-metastatic activity in uterine
      serous carcinoma in vitro.
AB  - Uterine serous carcinoma (USC) represents an aggressive histologic subtype of
      endometrial cancer. It is associated with a poor prognosis, and improved
      therapies for women battling USCs are greatly needed. ONC201 is an orally
      bioavailable, first-in-class small molecule that induces tumor necrosis factor
      related apoptosis-inducing ligand (TRAIL) independent of p53. ONC201 has
      demonstrated anti-tumorigenic activity in pre-clinical models of solid tumors
      through induction of apoptosis and inactivation of the AKT/MAPK pathways. Recent
      phase I and II clinical trials have shown that ONC201 is well tolerated and may
      have single agent activity in high grade glioma patients among others. We sought
      to determine the effects of ONC201 on cell proliferation in USC and identify the
      mechanisms by which ONC201 inhibits cell growth in this disease. ONC201 inhibited
      cell proliferation in a dose-dependent manner in ARK1, ARK2 and SPEC-2 cell
      lines. The anti-proliferative activity of ONC201 in ARK1 and SPEC-2 cells was
      associated with induction apoptosis independent of p53 via both a TRAIL mediated
      apoptotic pathway and a mitochondrial apoptosis pathway. Treatment with ONC201
      resulted in significant reduction in adhesion and invasion as well as inhibition
      of the AKT and MAPK pathways. In addition, ONC201 markedly potentiated the anti
      tumorigenic effects of paclitaxel in USC cells. Our results suggest that ONC201
      has significant anti-proliferative and anti-metastatic effects in USC cells
      through both induction of apoptosis and inhibition of the AKT and MAPK pathways.
      ONC201 and paclitaxel are a promising therapeutic combination in USC cells. Thus,
      ONC201 should be evaluated as a single agent and as a therapeutic partner with
      paclitaxel in future clinical trials of USC.

PMID- 30210925
TI  - Nomogram for predicting survival in triple-negative breast cancer patients with
      histology of infiltrating duct carcinoma: a population-based study.
AB  - Triple-negative breast cancer (TNBC) represents around 15%-20% of newly diagnosed
      breast cancer and is more aggressive than other breast cancer sub-types.
      Infiltrating duct carcinoma (IDC) is the most common type of TNBC. Nomogram is a
      valuable tool for prognosis prediction by integrating different biological and
      clinical variables. The purpose of current study was to evaluate the prognostic
      value of clinical factors of TNBC patients with IDC histology type and construct
      nomograms for their outcome prediction. The cohort was selected from
      Surveillance, Epidemiology, and End Results (SEER) program. Univariate and
      multivariate analyses were performed using Cox proportional hazards regression
      model to evaluate the prognostic value of involved variables. Nomogram was
      constructed from the multivariate logistic regression model to combine all the
      prognostic factors to predict the 1-year and 3-year prognosis of TNBC patients
      with histology of IDC. Internal validation of nomogram was tested by
      discrimination and calibration. We identified 14,538 patients with the median and
      max survival time was 28 months and 59 months, respectively. There were 1,592
      deaths, accounting for 10.9% of the cohort. Multivariate analyses showed that
      grade, tumor stage, tumor size, regional nodes positive, marital status,
      experience of radiotherapy or chemotherapy were independent prognostic factors of
      IDC of TNBC. Eleven variables were combined to construct 1-year and 3-year
      nomograms. It was revealed that the C-index of the nomograms was 0.763 and the
      calibration curves showed good agreement between the nomogram prediction and
      actual observation. Current study was the first one to construct nomograms of
      TNBC patients with IDC histology, which could help physicians to identify
      patients at high risk for intensive treatment or follow-up.

PMID- 30210926
TI  - MicroRNA-506 suppresses invasiveness and metastasis of human hepatocellular
      carcinoma cells by targeting IL8.
AB  - MicroRNAs (miRNAs) have been reported to be involved in tumor metastasis. In this
      study, we investigated the function of miR-506 in the metastasis of human
      hepatocellular carcinoma (HCC). We found that miR-506 is significantly
      downregulated in the primary tissue of metastatic HCC and in highly metastatic
      HCC cell lines. Overexpression of miR-506 suppressed HCC cell migration,
      invasion, and metastasis both in vitro and in vivo. Furthermore, miR-506 was
      found to specifically target the 3' untranslated region (3'-UTR) of interleukin 8
      (IL8) mRNA. Spearman's correlation analysis revealed that miR-506 expression
      inversely correlated with IL8 mRNA and protein expression in HCC tissue samples.
      IL8 treatment reversed miR-506-induced suppression of HCC cell migration and
      invasiveness. Thus, miR-506 acts as a tumor suppressor that may inhibit the
      migration, invasiveness, and metastasis of HCC cells by targeting IL8.

PMID- 30210924
TI  - Co-inhibition of TIGIT, PD1, and Tim3 reverses dysfunction of Wilms tumor protein
      1 (WT1)-specific CD8+ T lymphocytes after dendritic cell vaccination in gastric
      cancer.
AB  - Dendritic cell (DC) vaccines have been shown to stimulate tumor antigen-specific
      CD8+ T cells; however, this strategy has demonstrated variable clinical efficacy
      likely due to immune escape mechanisms that can induce tumor-specific CD8+ T cell
      dysfunction. Herein, we evaluated the functional characteristics of DC vaccine
      induced CD8+ T cells with regard to immune checkpoint inhibitors in gastric
      cancer patients who were administered Wilms tumor protein-1 (WT1)-targeted DC
      vaccine. We observed the upregulation of the inhibitory molecule, TIGIT and the
      inhibitory T cell co-receptors PD1 and Tim3 in limiting WT1-specific CD8+ T cell
      growth and function in GC patients. TIGIT-expressing PD1+Tim3- CD8+ T cells were
      the largest subset, while TIGIT+PD1+Tim3+ was the most dysfunctional subset of
      WT1-specific CD8+ T cells in gastric cancer patients. Importantly, the co
      inhibition of TIGIT, PD1, and Tim3 pathways enhanced the growth, proliferation,
      and cytokine production of WT1-specific CD8+ T cells. In conclusion, our data
      suggests that targeting TIGIT, PD1, and Tim3 pathways may be important in
      reversing immune escape in patients with advanced gastric cancer.

PMID- 30210927
TI  - Combined treatment of cholangiocarcinoma with interventional radiofrequency
      hyperthermia and heat shock protein promoter-mediated HSV-TK gene therapy.
AB  - Cholangiocarcinoma is a most lethal malignancy frequently resistant to
      chemotherapy. Herpes simplex virus thymidine kinase/Ganciclovir (HSV-TK/GCV)
      suicide gene therapy is a promising approach to treat different cancers,
      including cholangiocarcinoma. However drawbacks including low therapeutic gene
      expression and lack of precise targeted gene delivery limit the wide clinical
      utilization of the suicide gene therapy. We attempted to overcome these
      obstacles. We established the "proof-of-principle" of this concept via serial in
      vitro experiments using human cholangiocarcinoma cells and then validated the new
      interventional oncology technique in vivo using mice harboring the same patient
      derived cholangiocarcinomas. Curative effects were evaluated by magnetic
      resonance imaging and confirmed by pathology and laboratory examinations.
      Intratumoral radiofrequency hyperthermia (RFH) significantly elevated the
      targeted expression of HSV-TK gene and further enhanced the therapeutic effects
      of direct intratumoral HSV-TK/GCV gene therapy, evident as the least number of
      survival tumor cells, smallest tumor size, and the highest apoptosis index in the
      combination treatment of HSV-TK plus RFH, compared to other control treatments.
      The novel combination of image-guided interventional oncology, RFH technology,
      and direct gene therapy may be valuable for the effective treatment of
      cholangiocarcinoma.

PMID- 30210928
TI  - Over-expression of IMPDH2 is associated with tumor progression and poor prognosis
      in hepatocellular carcinoma.
AB  - Inosine monophosphate dehydrogenase type II (IMPDH2) has been found to play
      critical roles in the development and progression of several human cancers.
      However, the expression of IMPDH2 and its clinical significance in hepatocellular
      carcinoma (HCC) is little known. The expression of IMPDH2 in HCC cell lines and
      tissues were evaluated by Western blotting (WB), quantitative real-time PCR (q
      PCR) and immunohistochemistry (IHC). We found that the expression of IMPDH2 was
      significantly up-regulated in HCC tissues than in adjacent non-tumorous tissues,
      and this was correlated with several clinicopathological features, including
      tumor multiplicity (P=0.001), TNM stage (P<0.001). Moreover, the Cox regression
      analysis suggested that the expression of IMPDH2 was an independent prognostic
      factor for overall survival (P<0.0001) and progression-free survival (P<0.0001).
      Further study showed that up-regulation of IMPDH2 expression increased the
      proliferation and tumorigenicity of HCC cells in vitro, by promoting cell growth
      rate, colony formation. Together, our results demonstrated that the over
      expression of IMPDH2 was closely associated with poor survival outcome in
      patients with HCC and may present a novel prognostic and therapeutic target for
      this disease.

PMID- 30210929
TI  - Diffusion MRI biomarkers predict the outcome of irreversible electroporation in a
      pancreatic tumor mouse model.
AB  - The purpose of this work is to explore the potential contribution of diffusion
      MRI to predict the effects of irreversible electroporation (IRE) in a pancreatic
      ductal adenocarcinoma (PDAC) mouse model. Thirteen mice were injected with Panc
      02 PDAC cells in both flanks. One tumor was treated with IRE when it reached a
      diameter of about 5 mm. T2- and diffusion-weighted MRI sequences were acquired
      before IRE treatment and 1, 3 and 7 days later. The mice were euthanized 1 day (n
      = 6) or 2 weeks (n = 7) after treatment. The tumors were excised and stained with
      H&E, caspase-3, CD-3, F4/80. The volume and the mean and standard deviation of
      the apparent diffusion coefficient (ADC) were compared between treated and
      untreated lesions and correlated with histology-derived measures. At 1-day post
      treatment, a dramatic ADC increase (+50.81%, P < 0.05) was found in ablated
      lesions, strongly correlated with apoptosis (tau = 0.90). At later time points
      the ADC returned to pre-treatment values, though histopathology showed a quite
      different scenario compared to the untreated controls. The ADC standard deviation
      measured within the treated tumors 1 day after IRE treatment had a strong
      negative correlation with the number of tumor cells found 14 days later (tau =
      0.80). There was also a strong correlation between 1-day ADC and 14-day apoptosis
      in untreated tumors (tau = 0.95). In conclusion, diffusion MRI is sensitive to
      the short-term effects of IRE in PDAC tumors, and can help predict the long-term
      treatment outcome.

PMID- 30210930
TI  - Induction of cells with prostate cancer stem-like properties from mouse induced
      pluripotent stem cells via conditioned medium.
AB  - Cancer stem cells (CSCs) that closely correlated with tumor growth, metastasis,
      provide a plausible explanation for chemoresistance and cancer relapse. CSCs are
      usually isolated and enriched from carcinoma cells, which is inconvenient, low
      efficient, and even unreliable. Here, we converted mouse induced pluripotent stem
      cells (miPSCs) into prostate cancer stem-like cells with carcinoma
      microenvironment following exposure to conditioned medium (CM) derived from RM9,
      a mouse prostate cancer cell line. These transformed cells, termed as miPS-RM9CM,
      displayed CSCs properties, including spheroids morphology and expression of both
      stemness genes and cancer stem cells surface markers, such as Oct3/4, Sox2,
      Nanog, Klf-4, c-Myc, CD44, and CD133. In addition, in vivo transplantation
      experiment was performed to confirm the tumorigenicity. Furthermore, we used the
      model to assess conventional chemotherapeutic agent, docetaxel. The results
      showed that miPS-RM9CM cells exhibited increased resistance to docetaxel,
      however, high susceptibility to the cancer cell stemness inhibitor I (BBI-608).
      Our current study demonstrates that CM from cultured RM9 cells play a crucial
      role in the determination of cell fate from miPSCs to cancer stem-like cells and
      provide a potentially valuable system for the study of CSCs.

PMID- 30210931
TI  - Relationship between CD44high/CD133high/CD117high cancer stem cells phenotype and
      Cetuximab and Paclitaxel treatment response in head and neck cancer cell lines.
AB  - Recent evidence suggests that cancer stem cells (CSCs), a small population of
      cancer cells that are highly tumourigenic, capable of self-renewal and have the
      ability to differentiate into cells that constitute the tumor, are the "drivers"
      of local recurrence and metastatic spread and may be associated with resistant to
      conventional therapy. The objectives of the study are to identify and
      characterize two head and neck cancer cell lines with regard
      CD44high/CD133high/CD117high profile (CSCs) and CD44low/CD133low/CD117low profile
      (Non-CSCs); to investigate the influence of chemotherapy treatment in CSCs and
      compare with Non-CSCs; to evaluate CD44 and EGFR gene expression in CSCs.
      Fluorescent-activated cell sorting (FACS) using specific cell surface marker
      combination (CD44, CD117 and CD133) was performed to isolate CSCs of Non-CSCs
      from cell lines. The Wound Healing assay was performed to confirm the presence of
      CSCs. After, the CSCs subpopulation and Non-CSCs were cultured and exposed for 24
      h to Cetuximab and Paclitaxel treatment, separately. Cell proliferation was
      determined by MTS assay. CD44 and EGFR gene expression was quantified by
      quantitative real time PCR (qPCR) using TaqMan(r) Assay in both subpopulations.
      CSCs subpopulation untreated were considered as relative expression control. We
      firstly characterized CSCs in HN13 and HEP-2 cell lines with CD44, CD133 and
      CD117 biomarkers. We treated CSCs and Non-CSCs subpopulations with Cetuximab and
      Paclitaxel treatment and found that CSCs subpopulations demonstrated more
      resistance to Paclitaxel chemoterapy, when compared with Non-CSCs subpopulations
      of oral cancer cell line. These CSCs subpopulations presented up-regulation of
      CD44 gene and down-regulation of EGFR gene in oral cancer cell line, and down
      regulation of CD44 gene and up-regulation of EGFR gene in laryngeal cancer cell
      line when compared with Non-CSCs subpopulations. We conclude that the combination
      of CD44, CD133 and CD117 biomarkers have stem cell properties in both cell lines.
      CSCs has ability to resist to Paclitaxel treatment in oral cancer cell line. CSCs
      present high expression of CD44 gene and down expression of EGFR gene in oral
      cancer cell line. CSCs in laryngeal cell line present down expression of CD44
      gene and high expression of EGFR gene when compared with cells without
      characteristics of cancer stem cells.

PMID- 30210933
TI  - Vulnerabilities Associated with Post-disaster Declines in HIV-testing:
      Decomposing the Impact of Hurricane Sandy.
AB  - Introduction: Using Interrupted Time Series Analysis and generalized estimating
      equations, this study identifies factors that influence the size and significance
      of Hurricane Sandy's estimated impact on HIV testing in 90 core-based statistical
      areas from January 1, 2011 to December 31, 2013. Methods: Generalized estimating
      equations were used to examine the effects of sociodemographic and storm-related
      variables on relative change in HIV testing resulting from Interrupted Time
      Series analyses. Results: There is a significant negative relationship between
      HIV prevalence and the relative change in testing at all time periods. A one unit
      increase in HIV prevalence corresponds to a 35% decrease in relative testing the
      week of the storm and a 14% decrease in relative testing at week twelve. Building
      loss was also negatively associated with relative change for all time points. For
      example, a one unit increase in building loss at week 0 corresponds with an 8%
      decrease in the relative change in testing (p=0.0001) and a 2% at week twelve
      (p=0.001). Discussion: Our results demonstrate that HIV testing can be negatively
      affected during public health emergencies. Communities with high percentages of
      building loss and significant HIV disease burden should prioritize resumption of
      testing to support HIV prevention.

PMID- 30210934
TI  - An Evaluation of Global Hazard Communication with Ethical Considerations.
AB  - INTRODUCTION: Despite the large number of hazards occurring every year, it is
      often only the most catastrophic and rapidly occurring hazards that are covered
      in detail by major news outlets. This can result in an under-reporting of smaller
      or slowly evolving hazards such as drought. Furthermore, the type or country in
      which the hazard occurs may have a bearing on whether it receives media coverage.
      The Public Health England (PHE) global weekly hazards bulletin is designed to
      inform subscribers of hazards occurring in the world in a given week regardless
      of location or type of natural hazard. This paper will aim to examine whether the
      bulletin is reporting these events in a way that matches a number of
      international disaster databases.  It will also seek to answer if biases within
      media outlets reporting of an event is impacting on the types of hazards and
      events being covered.  Through the analysis of data collected, it is hoped to be
      able to consider the ethical implications of such a bulletin service and provide
      recommendations on how the service might be improved in the future. METHODS: The
      study used a year's worth of global hazards bulletins sent by Public Health
      England.  These bulletins aim to communicate hazards in the form of compiled
      articles from news outlets around the world. Data from these bulletins was
      collected and analysed by hazard type and the country in which hazards occurred. 
      It was then compared to recognised hazard databases to assess similarities and
      differences in the hazards being reported via media or through dedicated hazard
      databases. The recognised hazard databases were those run by the Emergency Events
      Database (EM-DAT), European Civil Protection and Humanitarian Aid Operations
      (ECHO) and National Aeronautics and Space Administration (NASA) respectively.
      RESULTS: The PHE bulletin overall was found to be comparable to other global
      hazard or disaster databases in terms of hazards included by both country and
      type of hazard. The PHE bulletin covered a greater number of unique hazard events
      than the other databases and also covered more types of hazard. It also gave more
      frequent coverage to the United Kingdom and Canada than the other databases, with
      other countries appearing less frequently. More generally, the PHE bulletin and
      the databases it was compared to appear to focus more on hazards either occurring
      in developed countries or fast-onset ones such as landslides or floods. On the
      other hand, slow-onset hazards such as drought or those occurring in developing
      countries appear to be under-reported and are given less importance in both the
      bulletin and databases. DISCUSSION AND RECOMMENDATIONS: We recommend that the
      resources compared review their inclusion criteria and assess whether the
      discrepancies in hazard type and country can be ratified through changes in how
      hazards are assessed for inclusion. More research should be undertaken to assess
      whether similar findings arise when comparing databases in other areas within the
      remit of public health.

PMID- 30210932
TI  - The chick chorioallantoic membrane (CAM) as a versatile patient-derived xenograft
      (PDX) platform for precision medicine and preclinical research.
AB  - Patient-derived xenografts (PDX) are an increasingly valuable tool in oncology,
      providing biologically faithful models of many different cancer types, and
      potential platforms for the development of precision oncology approaches.
      However, PDX have primarily been established in immunodeficient rodent models,
      with accompanying cost and efficiency constraints that pose barriers to more
      widespread adoption. The chicken egg chorioallantoic membrane (CAM) is an
      alternative in vivo PDX model. We provide here a comprehensive review of studies
      that grafted primary human tissue, as opposed to cell lines, onto the CAM. Twenty
      publications met our criteria of having inoculated patient-derived tumor tissue
      onto the CAM. Successful engraftment has been reported for over a dozen tumor
      subtypes, supporting the appropriateness of the CAM as a PDX platform.
      Resemblance of xenografts to the original patient tumor, increased vascularity of
      the CAM following engraftment, and micrometastasis into the chick mesenchyme were
      frequently reported. Application of standard or experimental cancer therapies to
      xenografts has also been undertaken, with the discovery of both synergistic drug
      effects and positive associations between the assay and clinical outcome. The CAM
      provides opportunities for RNA and DNA based sequencing of patient tumors, and
      the ability to efficiently (in 5-10 days) test multiple targeted therapies on
      fragments derived from the same tumor. While routine use of the CAM-based PDX
      model would benefit from a more-complete understanding of the stromal environment
      of CAM xenografts and interaction with the developing avian immune system,
      current literature supports the model's potential as an efficient, scalable
      precision medicine platform.

PMID- 30210935
TI  - The 2016-2017 Chikungunya Outbreak in Karachi.
AB  - INTRODUCTION: Chikungunya is an incipient disease, caused by Chikungunya virus
      (CHKV) that belongs to genus alphavirus of the family Togaviridae. MATERIALS AND
      METHODS: In this study, during an outbreak of CHKV in Dec 2016 in Karachi,
      Pakistan, samples were collected from patients presenting with fever, tiredness
      and pain in muscles and joints. Total 126 sera were tested for the presence of
      Chikungunya infection through ELISA and Real-time Reverse Transcriptase PCR
      assay. RESULTS AND DISCUSSION: This study showed that approx 79.4% samples were
      positive for CHKV. To our knowledge, this is the first reported outbreak from
      last decades in which the presence of CHKV is confirmed in Karachi while
      affecting such large no. of individuals.. CONCLUSION: CHKV diagnosis should be
      considered by the scientists and clinicians as a differential diagnosis in
      febrile patients, and appropriate control strategies must be adopted for its
      surveillance.

PMID- 30210936
TI  - Health Care Transition Experiences of Males with Childhood-onset Duchenne and
      Becker Muscular Dystrophy: Findings from the Muscular Dystrophy Surveillance
      Tracking and Research Network (MD STARnet) Health Care Transitions and Other Life
      Experiences Survey.
AB  - Introduction: As the proportion of males with Duchenne muscular dystrophy (DMD)
      surviving into adulthood increases, more information is needed regarding their
      health care transition planning, an essential process for adolescents and young
      adults with DMD. The objective of this study was to describe the health care
      transition experiences of a population of males living with Duchenne or Becker
      muscular dystrophy (DBMD). Methods: The eligible participants, identified through
      the Muscular Dystrophy Surveillance Tracking and Research Network (MD STARnet)
      surveillance project, were 16-31 years old and lived in Arizona, Colorado,
      Georgia, Iowa, or western New York (n=258). The MD STARnet Health Care
      Transitions and Other Life Experiences Survey was conducted in 2013 and
      administered online or in a telephone interview. Sixty-five males (25%) completed
      the survey. Among non-ambulatory males, response differences were compared by age
      group. Statistical comparisons were conducted using Fisher's exact test, or when
      appropriate, the Chisquare test. Results: Twenty-one percent of non-ambulatory
      males aged 16-18 years, 28% of non-ambulatory males aged 19-23 years, 25% of non
      ambulatory males aged 24-30 years, and 18 ambulatory males had a written
      transition plan. Nineteen percent of non-ambulatory males aged 24-30 years had
      delayed or gone without needed health care in the past 12 months. Among non
      ambulatory males aged 24-30 years, 75% had cardiology providers and 69% had
      pulmonology providers involved in their care in the past 12 months. Twentyeight
      percent of non-ambulatory males aged 19-23 years and 25% of non-ambulatory males
      aged 24-30 years reported that they did not receive health care or other services
      at least once because they were unable to leave their home. Non-ambulatory males
      aged 16-18 years (29%) were less likely to have ever discussed how to obtain or
      keep health insurance as they get older compared to non-ambulatory males aged 24
      30 years (69%) (p <0.01). Discussion: This study identified potential barriers to
      the successful health care transition of males with DBMD. The results of this
      study may indicate a lack of targeted informational resources and education
      focused on supporting the transition of young men with DBMD as they age from
      adolescence into adulthood within the healthcare system. Future studies could
      determine the reasons for the potential barriers to health care and identify the
      optimal transition programs for males with DBMD. There are a few online resources
      on transition available to adolescents and young adults with special health care
      needs.

PMID- 30210937
TI  - Paradoxical Onset of Arrhythmic Waves from Depolarized Areas in Cardiac Tissue
      Due to Curvature-Dependent Instability.
AB  - The generation of abnormal excitations in pathological regions of the heart is a
      main trigger for lethal cardiac arrhythmias. Such abnormal excitations, also
      called ectopic activity, often arise from areas with local tissue heterogeneity
      or damage accompanied by localized depolarization. Finding the conditions that
      lead to ectopy is important to understand the basic biophysical principles
      underlying arrhythmia initiation and might further refine clinical procedures. In
      this study, we are the first to address the question of how geometry of the
      abnormal region affects the onset of ectopy using a combination of experimental,
      in silico, and theoretical approaches. We paradoxically find that, for any
      studied geometry of the depolarized region in optogenetically modified monolayers
      of cardiac cells, primary ectopic excitation originates at areas of maximal
      curvature of the boundary, where the stimulating electrotonic currents are
      minimal. It contradicts the standard critical nucleation theory applied to
      nonlinear waves in reaction-diffusion systems, where a higher stimulus is
      expected to produce excitation more easily. Our in silico studies reveal that the
      nonconventional ectopic activity is caused by an oscillatory instability at the
      boundary of the damaged region, the occurrence of which depends on the curvature
      of that boundary. The onset of this instability is confirmed using the
      Schrodinger equation methodology proposed by Rinzel and Keener [SIAM J. Appl.
      Math. 43, 907 (1983)]. Overall, we show distinctively novel insight into how the
      geometry of a heterogeneous cardiac region determines ectopic activity, which can
      be used in the future to predict the conditions that can trigger cardiac
      arrhythmias.

PMID- 30210938
TI  - Flower-mediated plant-butterfly interactions in an heterogeneous tropical coastal
      ecosystem.
AB  - Background: Interspecific interactions play an important role in determining
      species richness and persistence in a given locality. However at some sites, the
      studies, especially for interaction networks on adult butterflies are scarce. The
      present study aimed the following objectives: (1) determine butterfly species
      richness and diversity that visit flowering plants, (2) compare species richness
      and diversity in butterfly-plant interactions among six different vegetation
      types and (3) analyze the structure of butterfly-flowering plant interaction
      networks mediated by flowers. Methods: The study was developed in six vegetation
      types within the natural reserve of La Mancha, located in Veracruz, Mexico. In
      each vegetation type, we recorded the frequency of flower visits by butterflies
      monthly in round plots (of radius 5 m) for 12 months. We calculated Shannon
      diversity for butterfly species and diversity of interactions per vegetation
      type. We determined the classic Jaccard similarity index among vegetation types
      and estimated parameters at network and species-level. Results: We found 123
      species of butterflies belonging to 11 families and 87 genera. The highest number
      of species belonged to Hesperiidae (46 species), followed by Nymphalidae (28) and
      Pieridae (14). The highest butterfly diversity and interaction diversity was
      observed in pioneer dune vegetation (PDV), coastal dune scrub (CDS) and tropical
      deciduous flooding forest and wetland (TDF-W). The same order of vegetation types
      was found for interaction diversity. Highest species similarity was found between
      PDV-CDS and PDV-TDF. The butterfly-plant interaction network showed a nested
      structure with one module. The species Ascia monuste, Euptoieta hegesia and
      Leptotes cassius were the most generalist in the network, while Horama oedippus,
      E. hegesia, and L. cassius were the species with highest dependencies per plant
      species. Discussion: Our study is important because it constitutes a pioneer
      study of butterfly-plant interactions in this protected area, at least for adult
      butterflies; it shows the diversity of interactions among flowering plants and
      butterflies. Our research constitutes the first approach (at a community level)
      to explore the functional role of pollination services that butterflies provide
      to plant communities. We highlighted that open areas show a higher diversity and
      these areas shared a higher number of species that shaded sites. In the
      interaction networks parameters, our results highlighted the higher dependence of
      butterflies by the flowers on which they feed than vice versa. In conclusion, the
      plant species (as a feeding resource) seem to limit the presence of butterfly
      species. Thus, this protected area is highly relevant for Lepidoptera diversity
      and the interaction between these insects and flowering plants. We suggest that
      studying plant and butterfly diversity in tropical habitats will provide insight
      into their interspecific interactions and community structure.

PMID- 30210939
TI  - Biodiversity surveys reveal eight new species of freshwater crabs (Decapoda:
      Brachyura: Potamidae) from Yunnan Province, China.
AB  - Yunnan Province is known to host the highest species diversity of the true
      freshwater crabs in China; 50 species have been recorded from the province by
      2017. In 2004, our team conducted a biodiversity survey of the freshwater crabs
      in Yunnan Province to determine how well the diversity of crabs in the area has
      been characterized. We collected a total of 25 species, of which nine species
      proved to be new to science, and eight of which are described here. These include
      four species of the genus Indochinamon Yeo & Ng, 2007, two species of the genus
      Potamiscus Alcock, 1909, and one species each of the genera Pararanguna Dai &
      Chen, 1985, and Parvuspotamon Dai & Bo, 1994. The new species of Pararanguna and
      Parvuspotamon represent the second species of respective genera, which are here
      redefined. Detailed comparisons with morphologically allied species are provided.
      Photographs of the type specimens of their comparative species which are poorly
      illustrated in the literature are also provided to allow better understanding of
      their morphology. This study brings the number of the freshwater crabs of Yunnan
      Province to 58. Since about 13.8% of the number of species (eight out of 58
      species) is increased by surveys conducted within a relatively short period, it
      is most probable that the species diversity of this group is still understudied
      in Yunnan Province.

PMID- 30210940
TI  - Primary molt in Gruiforms and simpler molt summary tables.
AB  - Molt summary tables reveal the sequence and mode of flight-feather replacement
      and how these feathers are divided into independent replacement series. Tables
      for summarizing molt are relatively new, and the rules for generating them were
      first formally illustrated using data from a temperate passerine. However, this
      first illustration failed to address (i) species with primaries divided into more
      than one replacement series, (ii) species with stepwise primary replacement,
      which almost always involves incomplete annual replacement of the primaries, and
      (iii) species with incomplete annual replacement within molt series characterized
      by single-wave replacement. Here, we review complications that arise in
      developing molt summary tables for such cases and we offer solutions that remove
      ambiguity about the direction that molt proceeds within a replacement series and
      about the recognition of nodal and terminal feathers that mark the beginning and
      end of molt series. We use these modified molt summary tables to describe the
      sequence of primary replacement in four groups of Gruiform birds, a group for
      which primary replacement has been reported to proceed from the outermost primary
      toward the body, unlike most other birds. Eighty molting Grey-winged Trumpeters,
      Psophia crepitans, and 124 molting Limpkins, Aramus guarauna, show the sequence
      of primary replacement is proximal in both groups; furthermore, the primaries of
      trumpeters are divided into two replacement series, one beginning at the
      outermost primary P10, and the other beginning at P3. To further evaluate the
      extent of this highly unusual direction of replacement in Gruiforms, we cast the
      data (Stresemann & Stresemann, 1966) on primary replacement in upland rails
      (Rallidae) and flufftails (Sarothruridae) into molt summary tables; both also
      replace their primaries proximally, from outermost to innermost, suggesting that
      this mode of primary replacement may be characteristic of Gruiformes.

PMID- 30210941
TI  - The palaeoenvironment of the Upper Cretaceous (Cenomanian-Turonian) portion of
      the Winton Formation, Queensland, Australia.
AB  - The Winton Formation is increasingly recognised as an important source of
      information about the Cretaceous of Australia, and, more broadly, the
      palaeobiogeographic history of eastern Gondwana. With more precise dating and
      stratigraphic controls starting to provide temporal context to the geological and
      palaeontological understanding of this formation, it is timely to reassess the
      palaeoenvironment in which it was deposited. This new understanding helps to
      further differentiate the upper, most-studied portion of the formation
      (Cenomanian-Turonian) from the lower portions (Albian-Cenomanian), allowing a
      coherent picture of the ecosystem to emerge. Temperatures during the deposition
      of the Upper Cretaceous portion of the Winton Formation were warm, with high,
      seasonal rainfall, but not as extreme as the modern monsoon. The landscape was
      heterogeneous, a freshwater alluvial plain bestrode by low energy, meandering
      rivers, minor lakes and mires. Infrequent, scouring flood events were part of a
      multi-year cycle of drier and wetter years. The heavily vegetated flood plains
      supported abundant large herbivores. This was the final infilling of the great
      Eromanga Basin.

PMID- 30210942
TI  - Dietary diversity is inversely correlated with pre-pregnancy body mass index
      among women in a Michigan pregnancy cohort.
AB  - Background: During pregnancy, healthy maternal body weight and a nutritionally
      complete diet provide a favorable environment for fetal development. Yet nearly
      two-thirds of women of reproductive age in the United States (US) are either
      overweight or obese. The objective of this research was to investigate the
      relationship between a measure of dietary diversity and body mass index (BMI) in
      a sample of women enrolled in a US pregnancy cohort. Methods: Dietary data was
      obtained from one 24-hour dietary recall collected during the third trimester of
      pregnancy (n = 40). Pre-pregnancy BMI was calculated from pre-pregnancy weight
      and height self-reported by survey at the time of enrollment. Using the Minimum
      Dietary Diversity for Women (MDD-W) indicator developed by the Food and
      Agriculture Organization of the United Nations, dietary data was categorized and
      scored. Results: Overall, 35% of participants did not achieve minimum dietary
      diversity (MDD-W >=5). In addition, 45% of participants were obese, 35% were
      normal weight and 20% were overweight. Women with higher BMI had lower MDD-W
      scores than women with lower BMI (p < 0.05). The median MDD-W for both normal and
      overweight women was >=5 indicating that normal and overweight pregnant women
      tended to consume a diet that was high in micronutrients. Conversely, the median
      MDD-W for obese women was below 5 meaning these women tended to consume a diet
      that was low in micronutrient density. The most commonly consumed food group was
      grain. In addition, 75% of all participants consumed sweetened drinks.
      Individuals with an MDD-W score >=5, were more likely to have consumed dark green
      leafy vegetables, vitamin A-rich fruits or vegetables, other vegetables and other
      fruits than those with MDD-W scores <5. Discussion: In this study, we show that a
      food group diversity indicator that has been shown to reflect adequacy of
      micronutrient intake in populations from less economically developed countries
      may also be informative in US populations. Furthermore, these results reflect the
      importance of encouraging all pregnant women with less varied diets to consume
      more fruits and vegetables.

PMID- 30210944
TI  - A bathypelagic ostracod Conchoecissa nigromaculatus sp. nov. (Myodocopa,
      Halocyprididae) from the South China Sea.
AB  - Pelagic ostracods are one of the main groups of zooplankton and are abundant in
      marine ecosystems worldwide. The record of marine planktonic ostracod species in
      the central and southern part of the South China Sea accounts over for one-third
      of the total recorded marine planktonic ostracods in seas around China. In this
      study, we examined and compared the specimens from a recent cruise in this region
      that appeared to be different from previously described species of genus
      Conchoecissa, and then confirmed them as a new bathypelagic species Conchoecissa
      nigromaculatus. These specimens clearly differed from the other species of genus
      Conchoecissa with differences observed in the size, carapace, locations of
      glands, mandible, maxilla, sixth limb, and furca. In this species, mandibular
      coxal endite has no ventral finger process, maxilla has prominently large endites
      and has only two claws on the tip, the sixth limb has very simple endites, and
      this species has distinctive features not previously observed in the tribe
      Conchoeciini before. It is therefore necessary to emend the diagnosis of this
      group.

PMID- 30210945
TI  - Seasonal changes in the abundance and biomass of copepods in the south-eastern
      Baltic Sea in 2010 and 2011.
AB  - Background: Copepods are major secondary producers in the World Ocean. They
      represent an important link between phytoplankton, microzooplankton and higher
      trophic levels such as fish. They are an important source of food for many fish
      species but also a significant producer of detritus. In the terms of the role
      they play in the marine food web, it is important to know how environmental
      variability affects the population of copepods. Methods: The study of the
      zooplankton community in the south-eastern Baltic Sea conducted during a 24-month
      survey (from January 2010 to November 2011) resulted in the identification of 24
      invertebrate species (10 copepods, seven cladocerans, four rotifers, one
      ctenophore, one larvacean, and one amphipod). Data were collected at two stations
      located in the open sea waters of the Gulf of Gdansk: the Gdansk Deep (P1) (54
      degrees 50'N, 19 degrees 19'E) and in the western, inner part of the Gulf of
      Gdansk (P2) (54 degrees 32'N, 18 degrees 48.2'E). The vertical hauls were carried
      out with the use of two kinds of plankton nets with a mesh size of 100 um: a
      Copenhagen net (in 2010), and a WP-2 net (in 2011). Results: The paper describes
      the seasonal changes in the abundance and biomass of copepods, taking into
      account the main Baltic calanoid copepod taxa (Acartia spp., Temora longicornis
      and Pseudocalanus sp.). They have usually represented the main component of
      zooplankton. The average number of copepods at the P1 Station during the study
      period of 2010 was 3,913 ind m-3(SD 2,572) and their number ranged from 1,184 ind
      m-3 (in winter) to 6,293 ind m-3(in spring). One year later, the average count of
      copepods was higher, at 11,723 ind m-3(SD 6,980), and it ranged from 2,351 ind m
      3(in winter) to 18,307 ind m-3(in summer). Their average count at P2 Station in
      2010 was 29,141 ind m-3, ranging from 3,330 ind m-3(in March) to 67,789 ind m
      3(in May). The average count of copepods in 2011 was much lower at 17,883 ind m
      3, and it ranged from 1,360 ind m-3 (in April) to 39,559 ind m-3 (in May).
      Discussion: The environmental conditions of the pelagic habitat change in terms
      of both depth and distance from the shore. Although the qualitative (taxonomic)
      structure of zooplankton is almost identical to that of the coastal waters, the
      quantitative structure (abundance and biomass) changes quite significantly. The
      maximum values of zooplankton abundance and biomass were observed in the summer
      season, both in the Gdansk Deep and in the inner part of the Gulf of Gdansk.
      Copepods dominated in the composition of zooplankton for almost the entire time
      of the research duration. Quantitative composition of copepods at the P1 Station
      differed from the one at P2 Station due to the high abundance of Pseudocalanus
      sp. which prefers colder, more saline waters.

PMID- 30210943
TI  - Unconscious response inhibition differences between table tennis athletes and non
      athletes.
AB  - Background: Response inhibition is associated with successful sporting
      performance. However, research on response inhibition in athletes from open-skill
      sports has mainly focused on a consciously triggered variety; little is known
      about open-skill athletes' response inhibition elicited by unconscious stimuli.
      Methods: Here, we explored unconscious response inhibition differences between
      table tennis athletes (n = 20) and non-athletes (n = 19) using the masked go/no
      go task and event-related potentials technique (ERPs). Results: At the behavioral
      level, table tennis athletes displayed shorter go-response times (RTs) than non
      athletes in the conscious condition. Furthermore, table tennis athletes exhibited
      longer response time-slowing (RT-slowing) than non-athletes in the unconscious
      condition. At the neural level, table tennis athletes displayed shorter event
      related potential N2 component latencies than non-athletes for all conditions.
      More importantly, athletes displayed larger no-go event-related potential P3
      component amplitudes than non-athletes at both the conscious and unconscious
      levels. Discussion: The present study results suggested that table tennis
      athletes have superior conscious and unconscious response inhibition compared to
      non-athletes.

PMID- 30210947
TI  - The Potential Use of 11C-Choline Positron Emission Tomography/Computed Tomography
      to Monitor the Treatment Effects of Radium-223 in a Patient with Prostate Cancer.
AB  - We report here about a 59-year-old man with bone metastatic castration-resistant
      prostate cancer and biochemical progression, who underwent radium-223 (Ra-223)
      therapy, following previous treatment failure. Treatment response of osseous
      metastases was assessed with three 11C-choline positron emission
      tomography/computed tomography (PET/CT) scans at baseline, after three cycles for
      early monitoring, as well as after six cycles of radium-223 therapy. Pretreatment
      11C-choline PET/CT showed multiple areas of increased focal activity in multiple
      cervical, thoracic, and lumbar vertebrae as well as in both ribs, right ileum,
      and left ischium. Second 11C-choline PET/CT after three cycles showed increasing
      tumor activity in the existing lesions and the new uptake spots of thoracic
      spine, both ribs and left ileum. Third 11C-choline PET/CT at the end of the
      therapy showed further progression with new lesions of thoratic spine, sacrum,
      right rib, and right ileum. In this case, 11C-choline PET/CT after three cycles
      for early monitoring could predict the therapeutic response to Ra-223.

PMID- 30210948
TI  - A Switch of an Idea: Simultaneous High Tibial Osteotomy and Lateral Meniscal
      Allograft Transplantation.
AB  - High tibial osteotomy (HTO) has been regarded as an effective treatment modality
      for isolated medial compartment knee osteoarthritis (OA) with varus deformity.
      However, management for relatively young active patients with both varus-aligned
      medial compartment knee OA and symptomatic irreparable lateral meniscus tear can
      be challenging. In this situation, correction of varus alignment by HTO and
      restoring the function of the lateral meniscus by meniscal allograft
      transplantation (MAT) can be a possible solution. We present the clinical result
      and technical considerations for a case of varus-aligned medial compartment OA
      combined with lateral meniscus tear treated by simultaneously performed medial
      open wedge HTO and lateral MAT.

PMID- 30210946
TI  - Measurement matters: higher waist-to-hip ratio but not body mass index is
      associated with deficits in executive functions and episodic memory.
AB  - Background: The current study aimed to reconcile the inconsistent findings
      between obesity, executive functions, and episodic memory by addressing major
      limitations of previous studies, including overreliance on body mass index (BMI),
      small sample sizes, and failure to control for confounds. Methods: Participants
      consisted of 3,712 midlife adults from the Cognitive Project of the National
      Survey of Midlife Development. Executive functions and episodic memory were
      measured by a battery of cognitive function tests. Results: We found that higher
      waist-to-hip ratio was associated with deficits in both executive functions and
      episodic memory, above and beyond the influence of demographics, comorbid health
      issues, health behaviors, personality traits, and self-perceived obesity.
      However, higher BMI was not associated with deficits in executive functions and
      episodic memory. More importantly, these differential associations were robust
      and stable across adulthood. Discussion: Our findings confirm the association
      between obesity and episodic memory while highlighting the need for better
      measures of obesity when examining its associations with individual differences
      in cognitive functions.

PMID- 30210949
TI  - A Case of Isolated Gastrointestinal Histoplasmosis.
AB  - Histoplasmosis is a self-limited and asymptomatic disease in immunocompetent
      individuals. Patients with untreated human immunodeficiency virus (HIV) or immune
      suppression due to medications such as corticosteroids can present with
      disseminated and life-threatening infections. We present a case of a 60-year-old
      female that presented with recurrent diarrhea that was found to have isolated
      gastrointestinal (GI) histoplasmosis. The rarity of this case is due to the
      isolated colonic involvement and lack of respiratory symptoms (the portal of
      infection). In conclusion, clinicians should be aware of isolated histoplasmosis
      affecting the GI tract and careful endoscopic evaluation with adequate sampling
      is warranted to confirm the diagnosis.

PMID- 30210950
TI  - A Partial Anomalous Pulmonary Venous Connection in a Severely Symptomatic
      Patient, Is Surgery Always Recommended?
AB  - Partial anomalous pulmonary venous connection (PAPVC) is a rare cardiac anomaly
      occurring when a pulmonary vein drains into the right atrium, coronary sinus or a
      systemic vein creating a left-to-right shunt. Symptoms develop from right-sided
      fluid overload and pulmonary vascular disease. We report a rare case of a
      severely symptomatic patient with an incidentally discovered PAPVC in the setting
      of underlying severe pulmonary hypertension from multifactorial severe
      restrictive lung disease. Despite his worsening symptoms, a multi-disciplinary
      meeting decided against surgical intervention. Nine months after the decision was
      made, the patient showed no signs or symptoms of clinical deterioration. Prior
      studies recommend surgery for PAPVCs with evidence of right ventricular dilation,
      mild-to-moderate tricuspid regurgitation, or early stages of pulmonary vascular
      disease. However, our case demonstrates how decision making should consider the
      shunt's contribution to the overall clinical picture and underlying
      comorbidities. If a decision is made to defer surgical intervention, strict
      follow up and repeat re-evaluations for possible risk re-stratification and
      surgery reconsideration are warranted.

PMID- 30210951
TI  - Medical Students' Perception of the Usage of Lecture Recording Software.
AB  - BACKGROUND: Lecture recording software is a useful reference tool that allows
      students to revisit lectures and understand complicated concepts in higher
      education. It is also a useful tool for students with learning difficulties,
      allowing them to reference and learn the material at their own pace. A
      significant advantage of this tool is the accessibility of course material to the
      students off campus. This study attempted to learn the students' perception of
      the purpose, use, and benefit of lecture recording software at a medical school.
      METHODS: The study was conducted using a structured questionnaire delivered, via
      an Internet-based survey application in the Fall semester of 2017, to 105
      students attending the basic sciences courses. A web link was generated after the
      18-point questionnaire was uploaded to an online survey software. The link was
      communicated electronically to each student along with the date and time of the
      survey. The survey was anonymous. The results of the survey were summarized using
      descriptive statistics and graphical methods. Students were asked to submit
      voluntary, informed consent to participate in the study before attempting to
      answer the questionnaire. The institutional review board approved the research.
      RESULTS: The results showed 77% students used this resource to understand points
      they missed in the class, 75% of them relearned complex ideas/concepts, and 62%
      of them used it to rewrite class notes. Reportedly, the software was used by
      students (78%) who missed a class due to an illness or while attending clinical
      shadowing. Of the students, 87% agreed that the software is helpful because of
      its off-campus availability while 84% of the students liked the service, as it
      allowed them to listen to the lectures at their own pace. Many students (65%)
      felt that the service helped them score better in the exams, whereas 38% did not
      think the recordings was helpful to get the desired grade and 50% student felt it
      was time-consuming. CONCLUSION: Despite the time-consuming listening process,
      students expressed a positive opinion about the usefulness of this software.
      Recording and archiving class lectures could be a useful academic resource.
      Students could learn from these archived lectures before the class and engage in
      the discussion later, enhancing active learning. The result suggests that
      students should also use other study resources and methods to achieve the desired
      grades. The induction of this student service into a professional curriculum
      would enhance the students' satisfaction, effectiveness, and outcomes.

PMID- 30210952
TI  - Rheumatic Heart Disease with Multiple Systemic Emboli: A Rare Occurrence in a
      Single Subject.
AB  - Valvular heart disease is one of the more common diseases in low- and middle
      income countries, when associated with atrial fibrillation (AF), carries a risk
      of multisystemic embolizations. We report a case of 37-year-old man with multiple
      systemic emboli consisting of acute ischemic stroke, acute myocardial infarction,
      and acute limb ischemia. This is a rare occurrence in a single subject. The
      patient had a background of rheumatic heart disease (RHD) involving severe mitral
      stenosis (MS) with AF, who was not compliant with his medications. A computed
      tomography (CT) scan of the head showed right-sided ischemic stroke involving
      more than one-third of the middle cerebral artery territory. An electrocardiogram
      (ECG) showed AF and ST-segment elevation in V4 to V6. Cardiac enzymes were
      elevated. A transthoracic echocardiogram demonstrated hypokinetic left
      ventricular anterolateral wall, severe MS, and a left atrial clot. An arterial
      Doppler of the right lower limb showed an occluding thrombus of the right common
      femoral artery and right popliteal artery with no flow in color Doppler. Patient
      adherence to medications in cases of RHD prevents devastating outcomes.

PMID- 30210953
TI  - Drug-induced Angioedema: A Rare Side Effect of Rosuvastatin.
AB  - Hydroxymethyl glutaryl coenzyme A reductase inhibitors (statins) are first-line
      medication for lowering serum cholesterol levels in the prevention of
      cardiovascular disease. Angioedema is the swelling of mucosa and submucosal
      tissue. There are no published cases of drug-induced angioedema involving
      rosuvastatin. We report a case of a 45-year-old female who presented with
      episodes of self-resolving edema of face, lips, and tongue after being on
      rosuvastatin. The patient denied any rash during these episodes and mentioned
      that self-medication with diphenhydramine did not relieve her symptoms. The
      patient was hemodynamically stable. The complement component 4 (C4), C1 esterase
      inhibitor, and complement component 1q (C1q) binding assay were within normal
      range. Therefore, the diagnosis of hereditary angioedema was effectively ruled
      out. The temporal relation between rosuvastatin and the development of angioedema
      and prompt resolution of symptoms after the drug discontinued suggest that
      rosuvastatin was the most probable culprit in the development of angioedema in
      our patient.

PMID- 30210954
TI  - Comparison of 11C-choline Positron Emission Tomography/Computed Tomography
      (PET/CT) and Conventional Imaging for Detection of Recurrent Prostate Cancer.
AB  - We aimed to compare 11C-choline positron emission tomography/computed tomography
      (PET/CT) with conventional imaging, including pelvic magnetic resonance imaging
      (MRI), contrast-enhanced chest, abdomen, and pelvic computed tomography (CT), and
      bone scintigraphy, for prostate cancer restaging. Thirty patients (median
      prostate-specific antigen [PSA: 11.8 ng/mL]) with suspected recurrent prostate
      cancer following definitive treatment underwent 11C-choline PET/CT and
      conventional imaging, including pelvic MRI, contrast-enhanced chest, abdomen, and
      pelvic CT, and bone scintigraphy. The results were compared with regard to
      patient- and lesion-based diagnostic performance for local recurrence, and for
      lymph node and bony metastases using receiver operating characteristic (ROC)
      analysis and McNemar's test. Documented local recurrence and node and bony
      metastases were present in 11 (36.7%), 10 (33.3%), and 17 (56.7%) cases,
      respectively, of the enrolled patients. Patient-based sensitivity / specificity /
      accuracy / area under the ROC curve for 11C-choline-PET/CT for diagnosing local
      recurrence were 90.9% / 94.7% / 93.3% / 0.975 and for conventional imaging were
      90.9% / 100% / 96.7% / 1.0. Those who underwent 11C-choline-PET/CT for node
      metastasis were 90.0% / 95.0% / 93.3% / 0.925 and for conventional imaging were
      70.0% / 95.0% / 86.7% / 0.905. Those who underwent 11C-choline-PET/CT for bone
      metastasis were 94.1% / 92.3% / 93.3% / 0.991 and who underwent conventional
      imaging were 94.1% / 84.6% / 90.0% / 0.982. No significant differences were
      observed among them. The lesion-based detection rate of 11C-choline PET/CT for
      local recurrences and node and bone metastases as compared to conventional
      imaging was 92.9% (13/14) vs. 92.9% (13/14); 87.1% (27/31) vs. 54.8% (17/31); and
      96.9% (219/226) vs. 90.3% (204/226) respectively, with significant differences
      noted for detection of node and bone lesions (p=0.0044 and p=0.00030,
      respectively). 11C-choline-PET/CT is more accurate in the detection of recurrent
      prostate cancer nodes and bony metastatic lesions compared to conventional
      imaging and has the advantage of restaging the disease in a single step.

PMID- 30210955
TI  - Prevalence and Predictors of Blood Pressure Screening in Karachi: A Cross
      sectional Study.
AB  - Background There is a lack of data about hypertension screening in low- to middle
      income countries. The primary objective of this study was to determine the
      prevalence and predictors of blood pressure (BP) screening in Karachi, Pakistan.
      The secondary objective was to identify ways to improve effective BP screening
      practices among the population at risk. Methods This cross-sectional study was
      conducted from November 2016 to May 2017. The sample population consisted of 2039
      residents of Karachi who were older than 18 years. A well-composed questionnaire
      was pilot tested and then used to assess their socio-demographic characteristics,
      personal attitude towards a healthy lifestyle, dietary habits, and BP screening
      practices. We used a chi-squared test as the primary statistical test. Results Of
      2039 people, 1627 had their BP checked at least once in their lifetime.
      Approximately, half of the participants had their BP checked on a yearly basis.
      Women had a higher rate (83.6%, n = 989) of getting their BP checked than men
      (74.5%, n = 636). A significant relationship was observed between BP screening
      and lifestyle practices such as physical activity (p = 0.00), hours of sleep (p =
      0.01), water intake (p = 0.01), and dining out (p = 0.03). Conclusion Current BP
      screening practices are inadequate amongst the urban population of Karachi. There
      is an urgent need for federal implementation of BP screening as well as awareness
      programs across the nation.

PMID- 30210956
TI  - Treatment of Odontoid Fractures: Recommendations of the Spine Section of the
      German Society for Orthopaedics and Trauma (DGOU).
AB  - Study Design: Narrative review. Objective: To establish recommendations for the
      treatment of odontoid fractures based on current literature and the knowledge of
      the experts of the Spine Section of the German Society for Orthopaedics and
      Trauma (DGOU). Methods: Narrative review of the literature. Analyzing treatment
      algorithms of German trauma and spine centers as members of the Spine Section of
      the German Society for Orthopaedics and Trauma (DGOU). Results: There are many
      influencing factors leading to appropriate treatment of odontoid fractures such
      as age, bone quality, arthrosis, classification, and type of the fracture.
      Conservative nonoperative treatment is appropriate for stable undislocated
      displaced odontoid fractures. Anterior osteosynthesis with 1 or 2 screws leads to
      good results in the classical unstable type II odontoid fracture in patients with
      good bone quality. However, modifiers have been identified by the working group
      leading to higher complication and failure rates. For these cases, more stable
      constructs and/or posterior approaches are indicated. Conclusions: Operation
      seems to be standard treatment for odontoid fractures. However, in the aged
      population, conservative treatment should be considered as morbidity and
      mortality rise significantly in the group of >75 years. Conservative treatment
      may also be started within stable nondislocated fractures, but then regular
      controls have to be performed. If operation is indicated, many influencing
      factors have to be considered for appropriate approach and technique. The
      classification of Anderson and D'Alonzo is still standard. To create an adequate
      treatment algorithm, dislocation displacement and instability have to be
      identified. Stable odontoid fractures are treated conservatively non-operatively,
      but if so regular controls have to be performed. Unstable and/or dislocated
      displaced odontoid fractures are treated by anterior osteosynthesis with 1 or 2
      screws. The technique is demanding and leads to elevated complication and failure
      rates if modifiers are apparent. In these cases, posterior instrumentation or
      fusion of C1 and C2 is favorable. In the aged population (>80 years), operative
      therapy is critical as postoperative morbidity complication and mortality rates
      rise significantly. As there is still some bias in the treatment algorithms, the
      working group recommends establishment of a prospective study to result in more
      objective statements.

PMID- 30210957
TI  - Treatment of Axis Ring Fractures: Recommendations of the Spine Section of the
      German Society for Orthopaedics and Trauma (DGOU).
AB  - Study Design: Narrative literature review and expert recommendation. Objective:
      To establish treatment recommendations for axis ring fractures based on the
      knowledge of the experts of the Spine Section of the German Society for
      Orthopaedics and Trauma. Methods: This recommendation summarizes the knowledge of
      the experts of the Spine Section of the German Society for Orthopaedics and
      Trauma with regard to the treatment of axis ring fractures based on a narrative
      literature review. Results: Typical "hangman's fractures" with bilateral
      separation of the neural arch from C2 and atypical "hangman's fractures" with
      irregular fracture morphology are described. Computed tomography is the "gold"
      standard used to detect and analyse these fractures adequately. Furthermore, the
      detection of vertebral artery integrity is necessary. To classify axis ring
      fractures, the Levine-Edwards or Josten classification is recommended. In
      particular, the integrity of the C2/3 disc and the integrity of the anterior
      longitudinal ligament are used to determine the treatment strategy. While Levine
      Edwards type I and type IIA (Josten type 1 and 2) fractures should be treated
      conservatively, Levine type II and type III (Josten type 3 and 4) fractures
      should be treated operatively. Levine-Edwards type II fractures will be
      predominately treated by anterior C2/3 fusion. Levine-Edwards type III fractures
      have to be primary reduced, if an anterior fusion is planned (anterior cervical
      discectomy and fusion [ACDF] C2/3). If a closed reduction of a type III fracture
      is impossible, an open reduction and posterior fixation/fusion is the treatment
      of choice. Conclusion: Conservative treatment is predominantly reserved for
      Levine-Edwards I and IIA fractures. Operative treatment should be performed in
      case of Levine-Edwards II and III fractures.

PMID- 30210958
TI  - Treatment of Injuries to the Subaxial Cervical Spine: Recommendations of the
      Spine Section of the German Society for Orthopaedics and Trauma (DGOU).
AB  - Study Design: Expert consensus. Objectives: To establish treatment
      recommendations for subaxial cervical spine injuries based on current literature
      and the knowledge of the Spine Section of the German Society for Orthopaedics and
      Trauma. Methods: This recommendation summarizes the knowledge of the Spine
      Section of the German Society for Orthopaedics and Trauma. Results: Therapeutic
      goals are a stable, painless cervical spine and protection against secondary
      neurologic damage while retaining maximum possible motion and spinal profile. The
      AOSpine classification for subaxial cervical injuries is recommended. The
      Canadian C-Spine Rule is recommended to decide on the need for imaging. Computed
      tomography is the favoured modality. Conventional x-ray is preserved for cases
      lacking a "dangerous mechanism of injury." Magnetic resonance imaging is
      recommended in case of unexplained neurologic deficit, prior to closed reduction
      and to exclude disco-ligamentous injuries. Computed tomography angiography is
      recommended in high-grade facet joint injuries or in the presence of vertebra
      basilar symptoms. A0-, A1- and A2-injuries are treated conservatively, but have
      to be monitored for progressive kyphosis. A3 injuries are operated in the
      majority of cases. A4- and B- and C-type injuries are treated surgically. Most
      injuries can be treated with anterior plate stabilization and interbody support;
      A4 fractures need vertebral body replacement. In certain cases, additive or pure
      posterior instrumentation is needed. Usually, lateral mass screws suffice. A
      navigation system is advised for pedicle screws from C3 to C6. Conclusions: These
      recommendations provide a framework for the treatment of subaxial cervical spine
      Injuries. They give advice about diagnostic measures and the therapeutic
      strategy.

PMID- 30210961
TI  - Spine Trauma Treatment: Recommendations of the German Society for Orthopaedics
      and Trauma (DGOU).

PMID- 30210960
TI  - Classification of Osteoporotic Thoracolumbar Spine Fractures: Recommendations of
      the Spine Section of the German Society for Orthopaedics and Trauma (DGOU).
AB  - Study Design: Expert opinion. Objectives: Osteoporotic vertebral fractures are of
      increasing medical importance. For an adequate treatment strategy, an easy and
      reliable classification is needed. Methods: The working group "Osteoporotic
      Fractures" of the Spine Section of the German Society for Orthopaedics and Trauma
      (DGOU) has developed a classification system (OF classification) for osteoporotic
      thoracolumbar fractures. The consensus decision followed an established pathway
      including review of the current literature. Results: The OF classification
      consists of 5 groups: OF 1, no vertebral deformation (vertebral edema); OF 2,
      deformation with no or minor (<1/5) involvement of the posterior wall; OF 3,
      deformation with distinct involvement (>1/5) of the posterior wall; OF 4, loss of
      integrity of the vertebral frame or vertebral body collapse or pincer-type
      fracture; OF 5, injuries with distraction or rotation. The interobserver
      reliability was substantial (kappa = .63). Conclusions: The proposed OF
      classification is easy to use and provides superior clinical differentiation of
      the typical osteoporotic fracture morphologies.

PMID- 30210959
TI  - Treatment of Fractures of the Thoracolumbar Spine: Recommendations of the Spine
      Section of the German Society for Orthopaedics and Trauma (DGOU).
AB  - Study Design: consensus paper with systematic literature review. Objective: The
      aim of this study was to establish recommendations for treatment of thoracolumbar
      spine fractures based on systematic review of current literature and consensus of
      several spine surgery experts. Methods: The project was initiated in September
      2008 and published in Germany in 2011. It was redone in 2017 based on systematic
      literature review, including new AOSpine classification. Members of the expert
      group were recruited from all over Germany working in hospitals of all levels of
      care. In total, the consensus process included 9 meetings and 20 hours of video
      conferences. Results: As regards existing studies with highest level of evidence,
      a clear recommendation regarding treatment (operative vs conservative) or
      regarding type of surgery (posterior vs anterior vs combined anterior-posterior)
      cannot be given. Treatment has to be indicated individually based on clinical
      presentation, general condition of the patient, and radiological parameters. The
      following specific parameters have to be regarded and are proposed as
      morphological modifiers in addition to AOSpine classification: sagittal and
      coronal alignment of spine, degree of vertebral body destruction, stenosis of
      spinal canal, and intervertebral disc lesion. Meanwhile, the recommendations are
      used as standard algorithm in many German spine clinics and trauma centers.
      Conclusion: Clinical presentation and general condition of the patient are basic
      requirements for decision making. Additionally, treatment recommendations offer
      the physician a standardized, reproducible, and in Germany commonly accepted
      algorithm based on AOSpine classification and 4 morphological modifiers.

PMID- 30210962
TI  - Nonsurgical and Surgical Management of Osteoporotic Vertebral Body Fractures:
      Recommendations of the Spine Section of the German Society for Orthopaedics and
      Trauma (DGOU).
AB  - Study Design: Prospective clinical cohort study (data collection); expert opinion
      (recommendation development). Objectives: Treatment options for nonsurgical and
      surgical management of osteoporotic vertebral body fractures are widely
      differing. Based on current literature, the knowledge of the experts, and their
      classification for osteoporotic fractures (OF classification) the Spine Section
      of the German Society for Orthopaedics and Trauma has now introduced general
      treatment recommendations. Methods: a total of 707 clinical cases from 16
      hospitals were evaluated. An OF classification-based score was developed to guide
      in the option of nonsurgical versus surgical management. For every classification
      type, differentiated treatment recommendations were deduced. Diagnostic
      prerequisites for reproducible treatment recommendations were defined:
      conventional X-rays with consecutive follow-up images (standing position whenever
      possible), magnetic resonance imaging, and computed tomography scan. OF
      classification allows for upgrading of fracture severity during the course of
      radiographic follow-up. The actual classification type is decisive for the score.
      Results: A score of less than 6 points advocates nonsurgical management; more
      than 6 points recommend surgical management. The primary goal of treatment is
      fast and painless mobilization. Because of expected comorbidities in this age
      group, minimally invasive procedures are being preferred. As a general rule,
      stability is more important than motion preservation. It is mandatory to restore
      the physiological loading capacity of the spine. If the patient was in a
      compensated unbalanced state at the time of fracture, reconstruction of the
      individual prefracture sagittal profile is sufficient. Instrumentation technique
      has to account for compromised bone quality. We recommend the use of cement
      augmentation or high purchase screws. The particular situations of injuries with
      neurological impairment; necessity to fuse; multiple level fractures; consecutive
      and adjacent fractures; fractures in ankylosing spondylitis are being addressed
      separately. Conclusions: The therapeutic recommendations presented here provide a
      reliable and reproducible basis to decide for treatment choices available.
      However, intermediate clinical situations remain with a score of 6 points
      allowing for both nonsurgical and surgical options. As a result, individualized
      treatment decisions may still be necessary. In the next step, the recommendations
      presented will be further evaluated in a multicenter controlled clinical trial.

PMID- 30210963
TI  - Spine Fractures in Ankylosing Diseases: Recommendations of the Spine Section of
      the German Society for Orthopaedics and Trauma (DGOU).
AB  - Study Design: Review of literature and case series. Objectives: Update and review
      of current treatment concepts for spine fractures in patients with ankylosing
      spinal disorders. Methods: Case presentation and description of a diagnostic and
      therapeutic algorithm for unstable spinal injuries with an underlying ankylosing
      spinal disorder (ASD) of the cervical and thoracolumbar spine. Results:
      Nondisplaced fractures can be missed easily using conventional X-rays. Thus,
      computed tomography (CT) scans are recommended for all trauma patients with ASD.
      In doubt or presence of any neurologic involvement additional magnetic resonance
      imaging (MRI) scans should be obtained. Spine precautions should be maintained
      all times and until definitive treatment (<24 h). Nonoperative fracture treatment
      is not recommended given the mechanical instability of the most commonly seen
      fracture patterns (AOSpine B- and C-type, M2) in patients with ASD and inherent
      high risk of secondary neurologic deterioration. For patients with ankylosing
      spondylitis (AS) or diffuse idiopathic hyperostosis (DISH) sustaining cervical
      spine fractures, a combined anterior-posterior instrumentation for fracture
      fixation is recommended. Closed reduction and patient positioning can be
      challenging in presence of preexisting kyphotic deformities. In the thoracolumbar
      (TL) spine, a posterior instrumentation extending 2 to 3 levels above and below
      the fracture level is recommended to maintain adequate reduction and stability
      until fracture healing. Minimally invasive percutaneous pedicle screws and cement
      augmentation can help to minimize the surgical trauma and strengthen the
      construct stability in patients with diminished minor bone quality (osteopenia,
      osteoporosis). Conclusions: Current concepts, treatment options, and
      recommendations of the German Orthopedic Trauma Society-Spine Section for spinal
      fractures in the ankylosed spine have been outlined.

PMID- 30210966
TI  - Mentorship, Education, and Teamwork in the Making of a Skull Base Surgeon: A
      Summary of the 28th Annual NASBS meeting: February 13-17, 2018; Loews Coronado
      Bay, Coronado, California, United States.

PMID- 30210964
TI  - Treatment of Atlas Fractures: Recommendations of the Spine Section of the German
      Society for Orthopaedics and Trauma (DGOU).
AB  - Study Design: Narrative review and expert recommendation. Objectives: To
      establish treatment recommendations for atlas fractures based on the knowledge of
      the experts of the Spine Section of the German Society for Orthopaedics and
      Trauma. Methods: Neither high-level evidence studies comparing conservative and
      operative management nor studies matching different operative treatment
      strategies exist. This recommendation summarizes the knowledge of the experts of
      the Spine Section of the German Society for Orthopaedics and Trauma with regard
      to the treatment of atlas fractures. Results: Most atlas fractures are the result
      of compression forces. A valuable morphological classification system has been
      described by Gehweiler. For an adequate diagnosis, a computed tomography is
      mandatory. To distinguish between stable and unstable type 3 injuries, it is
      necessary to evaluate the integrity of the transverse atlantal ligament (TAL)
      with magnetic resonance imaging and to classify the TAL lesions. The majority of
      atlas fractures are stable and will be successfully managed conservatively.
      Unstable atlas fractures (type 3b and sagittal split type 4 fractures) should be
      treated by surgical stabilization. Unstable atlas fractures (type 3b) with a
      midsubstance ligamentous disruption or severely dislocated ligamentous bony
      avulsions of the TAL can successfully be treated by a C1/2 fusion. Unstable atlas
      fractures (type 3b) with a moderately dislocated ligamentous bony avulsion of the
      TAL and sagittal split type 4 fractures may be treated by atlas osteosynthesis
      only. Conclusions: Whereas the majority of atlas fractures can be managed
      conservatively, in specific fracture patterns surgical treatment strategies have
      become the standard of care.

PMID- 30210965
TI  - Ammonium Ylide Mediated Cyclization Reactions.
AB  - The use of readily accessible ammonium ylides for (asymmetric) transformations,
      especially cyclization reactions, has received considerable attention over the
      past two decades. A variety of highly enantioselective protocols to facilitate
      annulation reactions have recently been introduced as an alternative to other
      common methods including S-ylide-mediated strategies. It is the intention of this
      short review to provide an introduction to this field by highlighting the
      potential of ammonium ylides for (asymmetric) cyclization reactions as well as to
      present the limitations and challenges of these methods.

PMID- 30210967
TI  - The Making of a Neurosurgeon: From Your Hands to Theirs.

PMID- 30210968
TI  - Impact of Dural Resection on Sinonasal Malignancies with Skull Base Encroachment
      or Erosion.
AB  - Objectives  (1) To determine the occult rate of dural invasion in patients with
      tumors extending to and/or eroding the bony anterior skull base but without
      evidence of dural invasion on preoperative imaging. (2) To determine the impact
      of dural resection and of skull base erosion on survival outcomes in this group
      of patients (without evidence of dural invasion upon preoperative imaging). Study
      Design  Retrospective study. Setting  Tertiary care academic center. Participants
      Patients with sinonasal malignancies with anterior skull base
      encroachment/erosion without dural invasion on preoperative imaging treated
      surgically. Main Outcome Measures  (1) Histopathologic disease in the dura in
      patients who had dural resection and (2) Oncologic outcomes (5-year local
      recurrence, dural recurrence, disease-specific survival, and overall survival) in
      patients with and without dural resection, and patients with and without skull
      base erosion. Results  Thirty-seven patients were included. The occult rate of
      dural invasion was 54%. Patients with dural resection had improved margin control
      versus those without dural resection (90% vs 56%, p  = 0.02). Dural resection
      improved 5-year overall survival only in patients with esthesioneuroblastoma
      compared with bony skull base resection alone (100% vs 75%, p  = 0.03). Patients
      with skull base erosion had reduced local control versus those without erosion
      (63% vs 93%, p  = 0.047). Conclusion  This study suggests a substantial rate of
      occult dural invasion despite no overt imaging findings. Dural resection may be
      associated with improved margin control, but no oncologic benefit except for
      esthesioneuroblastomas, although treatment heterogeneity and small sample size
      may limit conclusions.

PMID- 30210969
TI  - The Microsurgical Relationships between Internal Carotid-Posterior Communicating
      Artery Aneurysms and the Skull Base.
AB  - Objective  This study aimed to review the anatomical and clinical characteristics
      of internal carotid-posterior communicating artery (IC-PC) aneurysms, especially
      those located close to the skull base. Methods  The microsurgical anatomy around
      the posterior communicating artery (PComA) was examined in a dry skull and five
      formalin-fixed human cadaveric heads. The clinical characteristics of 37 patients
      with 39 IC-PC aneurysms, who were treated microsurgically between April 2008 and
      July 2016, were retrospectively reviewed. Results  The anterior clinoid process
      (ACP), as well as the anterior petroclinoidal dural fold (APF), which forms part
      of the oculomotor triangle, are closely related to the origin of the PComA. Among
      the 39 IC-PC aneurysms, anterior clinoidectomy was performed on 4 (10.3%) and a
      partial resection of the APF was performed on 2 (5.1%). Both of these aneurysms
      projected inferior to the tentorium, or at least part of the aneurysm's dome was
      inferior to the tentorium. Conclusion  Proximally located IC-PC aneurysms have an
      especially close relationship with the ACP and APF. We should be familiar with
      the anatomical relationship between IC-PC aneurysms and the structures of the
      skull base to avoid hazardous complications.

PMID- 30210970
TI  - Impact of Surgical Margin in Skull Base Surgery for Head and Neck Sarcomas.
AB  - Objective  This study aimed to determine the adequate resection margin in skull
      base surgery for head and neck sarcoma. Design  We retrospectively reviewed 22
      sarcomas with skull base invasion. Induction chemotherapy, followed by surgery
      and postoperative radiotherapy and adjuvant chemotherapy, was performed in 18
      patients with chemosensitive sarcomas, and surgery with or without postoperative
      radiotherapy was performed in four patients with chemoresistant sarcomas. Radical
      resection was performed in patients with chemosensitive sarcomas with a poor
      response to induction chemotherapy and in patients with chemoresistant sarcomas.
      Conservative resection with close surgical margin was performed in patients with
      chemosensitive sarcomas with a good response to induction chemotherapy. Setting
      and Participants  This single-centered retrospective study included patients from
      the National Cancer Center Hospital, Japan. Results  The response to induction
      chemotherapy was significantly associated with the 3-year local control rate
      (LCR; good response versus poor response: 100% versus 63%, p  = 0.048). Patients
      with a good response to chemotherapy had a favorable local prognosis even when
      the local therapy was conservative resection. In radical skull base surgery,
      patients whose surgical margins were classified as "wide margin positive" had
      significantly poorer 3-year LCR than did patients with "margin negative" or
      "micro margin positive" margins (25% versus 83%, p  = 0.014). Conclusion 
      Conservative resection with close surgical margins might be acceptable for
      chemosensitive sarcomas with a good response to chemotherapy. Resection margin
      status was an important predictive factor for local recurrence after radical
      skull base surgery. Microscopic microresidual tumor might be controlled by
      postoperative treatment.

PMID- 30210971
TI  - Cranial Nerve Preservation Following Surgical Treatment for Epidermoid Cysts of
      the Posterior and Middle Fossae.
AB  - Epidermoid cysts are rare lesions, accounting for 0.2 to 1.8% of all intracranial
      tumors. They most commonly occur in the cerebellopontine angle where they may
      cause a breadth of neurologic complications due to mass effect on the nearby
      cranial nerves (CN), vascular structures, and the brain stem. Treatment of
      epidermoid cysts is surgical, with the goal of complete resection using
      microsurgical technique and even more importantly preservation of the involved
      CNs, vasculature, and brain parenchyma. Successful surgery can result in total
      resolution of symptoms, but, in certain situations, may not be advisable due to
      adherence, scarring, or inflammation making dissection of CN fascicles difficult
      and possibly hazardous. We conducted a retrospective review from 1998 to 2016 and
      compiled a series of 28 skull base epidermoid cysts operated on at our
      institution. Cases were evaluated for presenting symptoms, history of prior
      resection, and postoperative results including CN function, extent of resection,
      residual tumor, and need for reoperations. The average tumor size (largest
      diameter) was 3.9 cm with a range of 1 to 7cm. Eighteen of twenty-eight (64%)
      patients underwent a gross total resection and ten underwent subtotal resection.
      No patients, whether presenting with CN deficits or not, experienced permanent
      worsening of CN function following surgery. Complete resection of epidermoid
      cysts should remain a high priority of therapy, but, in our opinion, preservation
      of CN function should be a primary goal, determining the extent of resection to
      provide patients with the highest quality of life possible following surgery.

PMID- 30210972
TI  - Transmastoid Repair of Spontaneous Cerebrospinal Fluid Leaks.
AB  - Objective  Determine the efficacy of using a purely transmastoid approach for the
      repair of spontaneous cerebrospinal fluid (CSF) leaks and further elucidate the
      relationship of elevated body mass index (BMI) and skull base thickness in our
      patient population. Method  We conducted a retrospective chart review of patients
      treated for spontaneous temporal bone CSF leaks at our tertiary care institution
      from the years 2006 to 2015. Cases were categorized as primary or secondary. We
      analyzed success rates, length of stay, use of lumbar drains, BMIs, and rates of
      meningitis. Skull base thickness was compared with BMI in each case. Results  We
      identified 26 primary operations for spontaneous CSF leaks and 7 secondary
      operations. Twenty-three of 33 repairs were performed via the transmastoid
      approach alone with an 87% success rate (20/23). Of the10 repairs including a
      middle cranial fossa (MCF) or combined MCF-transmastoid approach, 2 failed for an
      80% success rate (8/10). Five transmastoid repairs underwent placement of a
      lumbar drain versus all 10 repairs employing an intracranial exposure. Average
      length of stay for those undergoing a transmastoid approach (1.7 days) was
      significantly shorter than for patients undergoing a MCF repair (6.3 days). Four
      patients presented with meningitis. Average BMI was 35.3. No correlation was
      established between BMI and skull base thickness ( R2  = 0.00011). Conclusion 
      The transmastoid approach is effective in the majority of cases and prevents the
      need for an intracranial operation, resulting in lower morbidity and a shorter
      length of stay. We believe that this is the preferred primary approach in most
      patients with spontaneous CSF leaks.

PMID- 30210973
TI  - Extended Retrosigmoid Approach for Cerebellopontine Angle Meningiomas: Operative
      Technique and Results-A Series of 28 Patients.
AB  - Background  The purpose of this article is to describe our approach, surgical
      strategies, and results for resection of meningiomas located at cerebellopontine
      angle (CPA). Methods  We retrospectively identified 28 patients with CPA
      meningiomas operated by the extended retrosigmoid approach. This approach
      incorporates a generous mastoidectomy and the sigmoid sinus exposure. Results 
      The mean age was 33.8 years, with a follow-up of 12.5 years. Gross total removal
      (GTR) was achieved in 22 (78.5%) patients with low surgical mortality, acceptable
      morbidity, and recurrence rate of 7.1% (2 patients). Conclusion  The extended
      retrosigmoid approach enhances the exposure of the CPA and posterior fossa
      cisterns and increases the surgical angle of maneuverability. This approach
      provides adequate access even to extensive CPA meningiomas, enabling, in most of
      cases, GTR to be safe and effective. The extended retrosigmoid approach used in
      this group of patients is an alternative to more extensive cranial base
      approaches.

PMID- 30210974
TI  - Volumetric Analysis of Endoscopic and Maxillary Swing Surgical Approaches for
      Nasopharyngectomy.
AB  - Objectives/Hypothesis  The endoscopic endonasal approach (EEA) for
      nasopharyngectomy is an alternative to the maxillary swing approach (MSA) for
      selected recurrent nasopharyngeal carcinomas (NPC). We compare the access between
      these approaches. Methods  Three cadaver specimens were used to compare access
      volumes of the EEA and MSA. Exposure volumes were calculated using image guidance
      registration to cone beam computed tomography and tracking of accessible tissue
      with volumetric quantification. The area of exposure to the carotid artery was
      measured. Results  The MSA provided higher volumes for access volume compared
      with the EEA (66.6 vs 39.1 cm 3 , p  = 0.009). The working area was larger in the
      MSA (80.2 vs 56.9 cm 2 , p  = 0.06). The exposure to the carotid artery was
      higher in the MSA (1.88 vs 1.62 cm 2 , p  = 0.04). The MSA provided larger volume
      of exposure for tumors of the parapharyngeal space with exposure below the
      palate. Conclusions  This study suggests that the MSA for nasopharyngectomy
      provides a larger volume of exposure. However, much of the increased exposure
      relates to exposure of the parapharyngeal space below the palate. The EEA
      provides adequate access to superior anatomical structures.

PMID- 30210975
TI  - Three-Dimensional Volumetric Segmentation of Pituitary Tumors: Assessment of
      Inter-rater Agreement and Comparison with Conventional Geometric Equations.
AB  - Background  The assessment of pituitary tumor (PT) volume is important in the
      treatment and follow-up of patients with PT. Previously, PT volume estimation has
      been performed by conventional geometric equations (CGE) such as abc/2
      (simplified ellipsoid volume equation) and 4pir 3 /3 (sphere), both presuming a
      symmetric tumor shape, which occurs uncommonly in patients with PT. In contrast,
      three-dimensional (3D) voxel-based software segmentation takes the irregular and
      asymmetric shapes that PTs often possess into account and might be a more
      accurate method for PT volume segmentation. The purpose of this study is twofold.
      (1) To compare 3D segmentation with CGE for PT volume estimation. (2) To assess
      inter-rater reliability in 3D segmentation of PTs. Methods  Nineteen high
      resolution (1mm slice thickness) T1-weighted MRI examinations of patients with PT
      were independently analyzed and manually segmented, using the software ITK-SNAP,
      by two certified neuroradiologists. Concurrently, the volumes of the PTs were
      estimated with abc/2 and 4pir 3 /3 by a clinician, and the results were compared
      with the corresponding segmented volumes. Results  There was a significant
      decrease in PT volume attained from the segmentations compared with the
      calculations made with abc/2 ( p  < 0.001, mean volume 18% higher than
      segmentation) and 4pir 3 /3 ( p  < 0.001, mean volume 28% higher than
      segmentation). The intraclass correlation coefficient (ICC) for the two sets of
      segmented PTs was 0.99. Conclusion  CGE ( abc/2 and 4pir 3 /3 ) significantly
      overestimates PT volume compared with 3D volumetric segmentation. The inter-rater
      agreement on manual 3D volumetric software segmentation is excellent.

PMID- 30210976
TI  - Macrophage Density Predicts Facial Nerve Outcome and Tumor Growth after Subtotal
      Resection of Vestibular Schwannoma.
AB  - Introduction  Vestibular schwannoma (VS) behavior following subtotal resection
      (STR) is highly variable. Overall progression rates have been reported as high as
      44%, and optimal treatment is controversial. Correspondingly, identification of a
      reliable clinical or pathologic marker associated with progression after STR
      would help guide decision-making. Methods  A prospectively maintained
      institutional VS registry from 1999 to 2014 was retrospectively reviewed for
      sporadic VS patients who underwent primary STR without preceding stereotactic
      radiosurgery (SRS) by a single neurosurgery-neurotology team. Primary endpoints
      included tumor progression and postoperative facial nerve function. Pathologic
      specimens were stained for Ki67, CD68, S100, and SOX10 and were quantitated by
      digital imaging analysis. Macrophage density was defined as the ratio of CD68 +
      macrophages to S100 + macrophages and Schwannian tumor cells. Clinical outcomes
      were correlated with pathologic markers. Results  Forty-six patients met the
      study inclusion criteria. Thirteen (28%) progressed during a mean 57 months of
      follow-up (range 15-149). Favorable postoperative facial nerve function (House
      Brackmann I-II) was achieved in 37 (80%). CD68 + cells were present at
      significantly higher concentrations in tumors that progressed ( p  = 0.03).
      Higher macrophage density was significantly associated with both tumor
      progression ( p  = 0.02) and unfavorable facial nerve function ( p  = 0.02). Ki67
      percent positivity was not significantly associated with either primary endpoint
      ( p  = 0.83; p  = 0.58). Conclusions   Macrophage density may provide an
      important marker for individuals at the highest risk for progression of VS after
      STR, potentially prompting closer surveillance or consideration for upfront SRS
      following STR. This finding supports preceding conclusions that an intratumoral
      macrophage-predominant inflammatory response may be a marker for tumor growth and
      a potential therapeutic target.

PMID- 30210977
TI  - Fluoroscopy-Assisted Transnasal Onyx Occlusion of the Eustachian Tube for Lateral
      Skull Base Cerebrospinal Fluid Leak Repair.
AB  - Objectives  To describe transnasal Eustachian tube (ET) occlusion with a liquid
      embolic solution for lateral skull base cerebrospinal fluid (CSF) leaks. Design 
      A lateral skull base CSF fistula model was developed by the authors using fresh
      cadaveric heads. Using a transtympanic needle, regulated pressurized pigmented
      saline was continuously instilled into the middle ear space and visualized
      endoscopically in the nasopharynx. An angioembolization catheter was then placed
      through the cartilaginous ET orifice just medial to the bony ET. Under endoscopic
      and fluoroscopic guidance, a column of liquid embolic agent was deployed into the
      bony ET segment up to the middle ear space. Setting  Tertiary care academic
      center. Participants  Cadaveric specimens. Main Outcome Measures  Cessation of
      CSF flow after occlusion at supraphysiologic pressures. Results  In two cadavers,
      a CSF fistula model was developed and endoscopic visualization of irrigant flow
      into the nasopharynx was confirmed. Fluoroscopy provided adequate anatomic views
      of the ET and middle ear, in addition to dynamic views of embolization. Cessation
      of flow after occlusion was successfully achieved with pressures up to 25 mm Hg,
      which exceeds normal physiological intracranial pressure. Conclusion  Eustachian
      tube occlusion with a liquid embolic solution is feasible in a novel cadaveric
      CSF leak model. In the future, this relatively short, straightforward procedure
      may become an outpatient alternative to manage intermittent or low-flow CSF
      fistulae following lateral skull base surgery.

PMID- 30210978
TI  - Dural Invasion Predicts the Laterality and Development of Neck Metastases in
      Esthesioneuroblastoma.
AB  - Objectives  Neck metastases in patients with esthesioneuroblastoma (ENB)
      constitute the most significant predictor of poor long-term survival. Recently,
      researchers discovered the existence of dural lymphatic channels that drain to
      the cervical lymph nodes. From this physiologic basis, we hypothesized that
      patients with ENB who develop dural invasion (DI) would exhibit a proclivity for
      neck metastases. Design  Retrospective review. Setting  Tertiary referral center.
      Participants  All patients treated for ENB from January 1, 1994 to December 31,
      2015. Main Outcome Measures  Incidence, laterality, and recurrence rate of neck
      metastases by DI status. Results  Sixty-one patients were identified (38% female;
      median age 49, range, 10-80), 34 (56%) of whom had DI and 27 (44%) did not. Of
      patients with DI, 50% presented with or developed neck disease following
      treatment compared with just 22% of those without DI ( p  = 0.026). Bilateral
      neck disease was more common in patients with DI (11/34, 32%) compared with those
      without (2/27, 7%) ( p  = 0.018). Five-year regional recurrence-free survival
      rates were 88% for those without and 64% for those with DI ( p  = 0.022). Kadish
      C patients with DI were more likely to develop regional recurrence when compared
      with Kadish C without DI and Kadish A/B ( p  = 0.083). Further, Kadish C patients
      with DI displayed worse overall survival than Kadish C without DI and Kadish A/B.
      Kadish D patients displayed the worst overall survival. The difference in overall
      survival among these four groups was significant ( p  < 0.001). Conclusion  DI by
      ENB is associated with increased incidence of cervical nodal metastases,
      bilateral neck disease, worse regional recurrence-free survival, and poorer
      overall survival. These data support the division of Kadish C by DI status.

PMID- 30210979
TI  - Socioeconomic Factors Affecting Discharge Status of Patients with Uncomplicated
      Transsphenoidal Adenohypophysectomy.
AB  - Objectives  The number of transsphenoidal adenohypophysectomies (TSAs) surgeries
      has grown significantly since 1993. While there has been an overall decreasing
      trend in length of stay (LOS), socioeconomic factors may impact hospitalization.
      This study explores the impact of socioeconomic factors on LOS and total charges
      in uncomplicated patients undergoing TSA. Design  Retrospective cohort. Setting 
      2009 to 2013 Nationwide Inpatient Sample. Participants  Patients undergoing TSA
      without medical complications. Main Outcomes Measures  LOS and total charges.
      Results  A total of 6,457 patients were identified, of which 17.2% had secreting
      tumors. Patients with secreting tumors stayed 2.95 days versus those with
      nonsecreting tumors stayed 3.26 days ( p  < 0.001). Discharge to other than self
      care was the largest contributing variable for both subsets, increasing both LOS
      and total charges. Patient factors that drove longer LOS and increased total
      charges for both subsets included metropolitan domicile, having a lower median
      income, Hispanic ethnicity, and having an increased amount of Agency for
      Healthcare Research and Quality (AHRQ) comorbidity indices. Having private
      insurance predicted a shorter LOS and lower total charges. Conclusions  These
      results demonstrate that, even without complications, patients can be delayed in
      their discharge. While several socioeconomic factors significantly predict LOS
      and charges, the discharge disposition ultimately has the greatest effect. This
      suggests that efforts should focus on improving organizational factors such as
      coordination with social work and outside facilities to decrease LOS and charges
      for this patient population.

PMID- 30210980
TI  - A Multilayered Technique for Repair of the Suboccipital Retrosigmoid Craniotomy.
AB  - Objective  Our primary objective was to retrospectively review our single
      institution experience using an anatomic multilayered repair of the retrosigmoid
      suboccipital craniotomy. Our secondary objective was to review the existing body
      of literature on the repair of this craniotomy and compare our outcomes to
      previous results. Design  Retrospective review of 25 consecutive patients
      undergoing repair for the retrosigmoid craniotomy. Setting  University of
      California Davis Medical Center (2010-2016). Participants  A total of 25
      consecutive patients who underwent retrosigmoid craniotomy and repair. Exclusion
      criteria included patients who were under the age of 18 years. Main Outcome
      Measures  Main outcomes included incidence of postoperative headache,
      cerebrospinal fluid leak, and wound infections. Results  Postoperative headache
      was reported in two patients in this series (8%). None of the patients in the
      series developed cerebrospinal fluid leak or wound infections. Mean follow-up
      period was 16 months. Conclusion  Our multilayered anatomic repair after
      retrosigmoid suboccipital craniotomy results in favorable clinical results and
      may help reduce the risks associated with this operation.

PMID- 30210981
TI  - Complications of Nasoseptal Flap Reconstruction: A Systematic Review.
AB  - Objective  The nasoseptal flap (NSF) is considered the primary vascularized flap
      for reconstruction of dural defects with endoscopic endonasal surgery (EES) of
      the skull base. However, the complications and morbidities associated with this
      reconstructive flap are poorly understood. This article presents a systematic
      review of the complications and morbidities related to the use of the NSF in
      skull base surgery. Method  A systematic review of the literature based on
      published guidelines was performed to identify potential complications and
      morbidities related to the NSF. The MEDLINE and Embase databases were searched
      from January 1, 1950 to February 5, 2018. Results  Twenty-seven articles were
      identified. Reported complications were as follows: NSF necrosis (4 studies; [0
      1.3%]), mucocele formation (5 studies; [0-3.6%]), septal perforation (6 studies,
      [0-14.4%]), nasal dorsum collapse (2 studies, [0.7-5.8%]), effects on quality of
      life (QoL) (8 studies), and olfactory loss (11 studies). Conclusion  Although
      complications associated with the NSF may be underreported in the literature, the
      NSF appears to be a safe and reliable reconstructive flap in EES of the skull
      base.

PMID- 30210982
TI  - The Endoscopic Endonasal Management of Anterior Skull Base Meningiomas.
AB  - Introduction  The endoscopic endonasal approach (EEA) might seem an "unnatural"
      route for intradural lesions such as meningiomas. The aim of this study is to
      critically revise our management of anterior skull base meningiomas to consider,
      in what cases it may be advantageous. Material and Methods  Each consecutive case
      of anterior skull base meningioma operated on through an EEA or combined
      endoscopic-transcranial approach at our institution, between 2003 and 2017, have
      been included. Tumors were classified on the basis of their location and intra or
      extracranial extension. Follow-up consisted of an MRI (magnetic resonance
      imaging) and a clinical examination 3 months after the surgery and then repeated
      annually. Results  Fifty-seven patients were included. The most common location
      was the tuberculum sellae (62%), followed by olfactory groove (14%), planum
      sphenoidale (12%), and frontal sinus (12%). Among these, 65% were intracranial,
      7% were extracranial, and 28% both intra and extracranial. Radical removal was
      achieved in 44 cases (77%). Complications consisted in 10 CSF (cerebrospinal
      fluid) leaks (17.6%), 1 overpacking (1.7%), and 1 asymptomatic brain ischemia
      (1.7%). Visual acuity and campimetric deficits improved respectively in 67 and
      76% of patients. Recurrence rate was of 14%. Conclusions  EEA presents many
      advantages in selected cases of anterior skull base meningioma. However, it is
      hampered by the relevant risk of CSF leak. We consider that it could be
      advantageous for planum/tuberculum sellae tumors. Conversely, for olfactory
      groove or frontal sinus meningiomas, it can be indicated for tumors with
      extracranial extension, while its role is still debatable for purely intracranial
      forms as considering our surgical results, it could be advantageous for midline
      planum/tuberculum sellae tumors. Conversely, it can be of first choice for
      olfactory groove or frontal sinus meningiomas with extracranial extension, while
      its role for purely intracranial forms is still debatable.

PMID- 30210983
TI  - Surgical Treatment of Cavernous Sinus Lesion in Patients with Nonfunctioning
      Pituitary Adenomas via the Endoscopic Endonasal Approach.
AB  - Objective  The main purpose of this article is to assess the effectiveness and
      safety of surgery via the endoscopic endonasal approach (EEA) for cavernous sinus
      (CS) lesion in patients with nonfunctioning pituitary adenomas (NFPA). Design 
      Retrospective study. Setting  Keio University Hospital. Participants  Thirty
      patients who underwent CS surgery via the EEA between 2009 and 2017 for Knosp
      grade 4 NFPA with pre- and postoperative magnetic resonance imaging available for
      volumetric analysis. Main Outcome Measures  Clinical presentation, extent of
      resection, and surgical complications. Results  Gross total and near total
      resection of CS tumors was achieved in 12/30 (40%) cases of Knosp grade 4 NFPA.
      The average resection rate of CS lesions in these 30 patients was 73.5%; 77.3% in
      primary cases and 70.1% in recurrent cases that did not vary significantly.
      Preoperative visual disturbance and oculomotor nerve palsy improved in 12/19
      (63.1%) and 3/5 (60%) cases, respectively. Complications associated with CS via
      the EEA were postoperative cerebrospinal leakage (1/30, 3.3%), meningitis (1/30,
      3.3%), and transient cranial nerve palsy (2/30, 6.7%). These complications except
      a case of mild transient abducens nerve palsy occurred in recurrent cases with
      subdural lesions. Conclusions  Although the optimal management of CS lesions in
      NFPA is controversial, debulking via the EEA is an effective and safe option that
      improves neurological symptoms and enables effective adjuvant radiotherapy.
      Recurrent cases with subdural invasion are technically challenging, even using
      the EEA, and special care is required to avoid complications.

PMID- 30210984
TI  - Long-Term Outcomes of Patients with Squamous Cell Carcinoma of the Temporal Bone
      after Concomitant Chemoradiotherapy.
AB  - Objectives  This article aims to clarify the long-term outcomes of patients with
      squamous cell carcinoma of the temporal bone who underwent concomitant
      chemoradiotherapy (CCRT). Design and Setting  The study design was a
      retrospective chart review. Patients and Methods  From December 2001 to June
      2014, 23 patients with cancer of the temporal bone who were treated by CCRT at
      the Tohoku University Hospital and the Iwate Medical University Hospital were
      enrolled in this study. For advanced cancer of the temporal bone, a modified
      docetaxel, cisplatin, and 5-fluorouracil (TPF) regimen was used for CCRT. The
      long-term outcomes, including prognoses and late complications, were analyzed
      after CCRT of patients with cancers of the temporal bone. Results  The main long
      term complications were stenosis of the external auditory canal and conductive
      hearing loss. No harmful late complications were observed in these patients.
      Disease-specific survival rates were 84.9% for all patients, 100% for patients of
      stage I, II, and III ( n  = 10), and 75.5% for patients of stage IV ( n  = 13) at
      5 years. Conclusions  Our study showed that CCRT is an effective treatment choice
      for squamous cell carcinoma of the temporal bone. Furthermore, CCRT using the TPF
      regimen is a safe and effective initial treatment for patients with advanced
      cancers of the temporal bone.

PMID- 30210985
TI  - Boron Neutron Capture Therapy for High-Grade Skull-Base Meningioma.
AB  - Objectives  Boron neutron capture therapy (BNCT) is a nuclear reaction-based
      tumor cell-selective particle irradiation that occurs when nonradioactive Boron
      10 is irradiated with low-energy neutrons to produce high-energy alpha particles
      (10B [ n , alpha] 7Li). Possible complications associated with extended surgical
      resection render high-grade meningioma (HGM) a challenging pathology and skull
      base meningiomas (SBMs) even more challenging. Lately, we have been trying to
      control HGMs using BNCT. This study aims to elucidate whether the recurrence and
      outcome of HGMs and SBMs differ based on their location. Design  Retrospective
      review. Setting  Osaka Medical College Hospital and Kyoto University Research
      Reactor Institute. Participants  Between 2005 and 2014, 31 patients with
      recurrent HGM (7 SBMs) were treated with BNCT. Main Outcome Measures  Overall
      survival and the subgroup analysis by the anatomical tumor location. Results 
      Positron emission tomography revealed that HGMs exhibited 3.8 times higher boron
      accumulation than the normal brain. Although tumors displayed transient increases
      in size in several cases, all lesions were found to decrease during observation.
      Furthermore, the median survival time of patients with SBMs post-BNCT and after
      being diagnosed as high-grade were 24.6 and 67.5 months, respectively (vs non
      SBMs: 40.4 and 47.5 months). Conclusions  BNCT could be a robust and beneficial
      therapeutic modality for patients with high-grade SBMs.

PMID- 30210986
TI  - Safety and Efficacy of Preoperative Embolization in Patients with Meningioma.
AB  - Preoperative embolization for intracranial meningioma has remained controversial
      for several decades. In this study, we retrospectively reviewed our experience of
      embolization using particulate embolic material and coil to clarify the
      therapeutic efficacy, safety, and risk of complication. Methods  We reviewed 69
      patients who underwent embolization with particulate embolic material followed by
      surgical resection. An additional 6 procedures were included for patients in whom
      recurrence was treated, for a total of 75 procedures of preoperative
      embolization. We analyzed the following clinical data: age, sex, tumor size
      pathology, complications related to embolization, and surgeon's opinion on the
      intraoperative ease of debulking and blood transfusion. Embolization was
      performed mainly from the branches of the external carotid artery. Results  No
      allogenic blood transfusions were needed for any patients. The surgeon had the
      opinion that whitening and softening of the tumor allowed for easy debulking
      during decompression of the tumor in most of the patients. Hemorrhagic
      complications were seen in two patients after embolization. Emergency tumor
      removal was performed in both of those patients, and they were recovered well
      after surgery. Transient cranial nerve palsy was seen in one patient. One
      ischemic complication and one allergic complication occurred. Conclusion 
      Preoperative embolization could give us an advantage in surgery for meningioma.
      The procedure reduces intraoperative blood loss and operating time by softening
      the tumor consistency. However, we must pay attention to the possibility of
      embolic complications and keep the preparation of emergency craniotomy,
      particularly in patients with large meningiomas.

PMID- 30210987
TI  - Real-Time Navigation-Guided Drilling Technique for Skull Base Surgery in the
      Middle and Posterior Fossae.
AB  - Objective  The usefulness of the bony surface registration method for navigation
      system image-guided surgery in the lateral or prone position has been reported.
      This study was performed to evaluate the efficacy of our new real-time navigation
      guided drilling technique with bony surface registration for skull base surgery
      in the middle and posterior fossae. Methods  The study included 29 surgeries for
      skull base tumors that required drilling of the petrous bone between January 2015
      and December 2017 in Shinshu University Hospital. A navigation system was used
      for drilling of the petrous bone as follows: (1) some labyrinthine structures
      were marked by color in the source image and superimposed on the navigation image
      on the workstation preoperatively; (2) bony surface registration was performed
      with a three-dimensional (3D) skull reconstruction model in the operating room;
      (3) the petrous bone was drilled under navigation guidance with real-time view
      through confirmation of 3D color-marked labyrinthine structures with observation
      under a microscopic operative view. Results  Real-time identification of some
      structures in the petrous bone was performed, and adequate and precise drilling
      of the petrous bone was achieved without the risk of labyrinthine perforation or
      stress. Using this method, surgeons do not need to alternate their gaze between
      the surgical field and the navigation screen. Conclusions  Due to the development
      of bony surface registration, this new technique is useful for drilling petrous
      bone in the middle and posterior fossa skull base surgeries.

PMID- 30210989
TI  - Less Invasive Modified Extradural Temporopolar Approach for Paraclinoid Lesions:
      Operative Technique and Surgical Results in 80 Consecutive Patients.
AB  - Background  Extradural temporopolar approach for paraclinoid lesions can provide
      extensive and early exposure of the anterior clinoid process, and complete
      mobilization and decompression of the optic nerve and internal carotid artery,
      which can prevent intraoperative neurovascular injury. The present study
      investigated the usefulness of our less invasive modified technique and discussed
      its operative nuances. Methods  We retrospectively reviewed medical charts of 80
      consecutive patients with neoplastic (21 patients) and vascular lesions (59
      patients) who underwent the modified extradural temporopolar approach between
      September 2009 and March 2014. Results  Preoperative visual acuity worsened in 4
      patients (5.0%) and worsening of visual field function occurred in 10 patients
      (12.5%). Postoperative outcome was good recovery in 71 patients, moderate
      disability in 6, severe disability in 2, and death in 1 (due to reruptured
      aneurysm). No operation-related mortality occurred in the series. Conclusion 
      Less invasive modified extradural temporopolar approach is safe and can be
      recommended for the surgical treatment of deeply located aneurysms and skull base
      tumors to reduce the risk of intraoperative optic neurovascular injury.

PMID- 30210988
TI  - Fluorescein-Guided Surgery for Pediatric Brainstem Gliomas: Preliminary Study and
      Technical Notes.
AB  - Introduction  Brainstem gliomas (BsG) account for 10 to 15% of pediatric brain
      tumors. Surgery is the preferred treatment for focal and exophytic lesions.
      Sodium fluorescein has been proven safe and effective in resection of malignant
      brain tumors. Objective  The objective was to o analyze the safety and
      effectiveness of this approach, to evaluate intraoperative fluorescein imaging,
      and to measure the safety of chosen dose for pediatric patients. Methods  Twelve
      cases were enrolled between March 2014 and September 2016 in Beijing Tiantan
      Hospital. All of the patients received 2.5 mg/kg of sodium fluorescein before
      opening the dura; the intraoperative fluorescence enhancement was observed, and
      the degree of satisfaction and consistency with the neuronavigation were
      evaluated. Results  With a mean age of 7.5 years, there were eight cases located
      within the pontine, three in the medullary oblongata, and one in the tectal
      plate. Histological results were astrocytoma, glioblastoma, oligodendroglioma,
      and pilocytic astrocytoma. Under the fluorescein module of the microscope, the
      tumors were recognizable enough to help surgeons to discriminate the lesion from
      non-fluorescent tissue, with a consistency of 83% with the neuronavigation. Total
      removal was accomplished in nine cases, while the mean percentage of resection of
      the other cases was 93.7%. The Karnofsky performance score (KPS) showed no
      significant differences between pre-operation and discharge, but there was a
      difference between pre-operation and 6-month follow-up. Conclusion  The
      fluorescein-guided surgery is useful for demarcating the tumor margin and works
      well with other navigation and monitoring devices. A safe dose of sodium
      fluorescein (2.5 mg/kg) was proven effective for children.

PMID- 30210990
TI  - Muscular-stage Dissection during Far Lateral Approach and Its Transcondylar
      Extension.
AB  - Background  The far lateral approach includes exposure of the C1 transverse
      process, vertebral artery, posterior arch of the atlas, and occipital condyle. We
      designed a method for systematic muscular-stage dissection and present our
      experience with this approach. Operative Methods  We used a horseshoe scalp flap
      that was reflected downward and medially. The lateral muscle layers were
      separated layer to layer to expose the suboccipital triangle. The medial muscle
      layers were separated in the midline and reflected in a single layer. At this
      stage, the midline of the C1 process and the foramen magnum were identified. The
      rectus capitis posterior major muscle was reflected to expose the posterior arch
      of the atlas. The C1 transverse process and vertebral artery were identified by
      reflection of the superior oblique muscle. The occipital condyle was separated
      accordingly. Results  We used this method of muscular dissection in 10 patients
      (foramen magnum meningioma, n  = 5; hypoglossal schwannoma, n  = 2; others, n  =
      3). Systematic muscular-stage dissection facilitates identification of the
      anatomical landmarks with no vertebral artery injury. Gross total removal was
      obtained in all 9 patients with complex tumors. The patient with vertebral artery
      dissection successfully underwent proximal clipping. Conclusion  Our muscular
      stage dissection could contribute to safe and effective surgery for the far
      lateral approach.

PMID- 30210992
TI  - A Staged Strategy for Craniocervical Junction Chordoma with Combination of
      Endoscopic Endonasal Approach and Far Lateral Approach with Endoscopic
      Assistance: Case Report.
AB  - Objective  While the endoscopic endonasal approach (EEA) has gained widespread
      acceptance for the resection of clivus chordomas, conventional transcranial
      approaches still have a crucial role in craniocervical junction (CCJ) chordoma
      surgery. In repeat surgery, a carefully planned treatment strategy is needed. We
      present a surgical treatment plan combining an EEA and a far-lateral craniotomy
      with endoscopic assistance (EA) in the salvage surgery of a recurrent CCJ
      chordoma. Case Presentation  A 37-year-old woman who had undergone partial
      resection of a chordoma extending from the mid-clivus to the CCJ. Technique  A
      two-stage surgical intervention was planned. First, we opted for an EEA with the
      intention of removing only the extradural and medial compartments of the lesion.
      The rationale was to avoid intradural dissection of possibly adherent tissues
      from the previous procedures and to minimize the cerebrospinal fluid leak risk.
      One month after the first endonasal stage, a far lateral craniotomy was
      performed. After removal of the lateral mass and pedicle of C1, a large surgical
      corridor to the tumor was obtained. Tumor loculations disseminated in and around
      the CCJ and located in the areas blind to microscopic examination were then
      successfully resected with EA. An occipito-cervical fusion was then performed
      during the same procedure. Conclusion  In addition to the exact location and
      morphology of the tumor, history of previous surgery was an important factor in
      devising a treatment strategy in this case of clivus chordoma. EA was also found
      to be instrumental in improving the reach of the far lateral approach.

PMID- 30210991
TI  - The Changing Paradigm for the Surgical Treatment of Large Vestibular Schwannomas.
AB  - Objective  Planned subtotal resection followed by Gamma Knife surgery (GKS) in
      patients with large vestibular schwannoma (VS) has emerged during the past
      decade, with the aim of a better functional outcome for facial and cochlear
      function. Methods  We prospectively collected patient data, surgical, and
      dosimetric parameters of a consecutive series of patients treated by this method
      at Lausanne University Hospital during the past 8 years. Results  A consecutive
      series of 47 patients were treated between July 2010 and January 2018. The mean
      follow-up after surgery was 37.5 months (median: 36, range: 0.5-96). Mean
      presurgical tumor volume was 11.8 mL (1.47-34.9). Postoperative status showed
      normal facial nerve function (House-Brackmann I) in all patients. In a subgroup
      of 28 patients, with serviceable hearing before surgery and in which cochlear
      nerve preservation was attempted at surgery, 26 (92.8%) retained serviceable
      hearing. Nineteen had good or excellent hearing (Gardner-Robertson class 1)
      before surgery, and 16 (84.2%) retained it after surgery. Mean duration between
      surgery and GKS was 6 months (median: 5, range: 3-13.9). Mean residual volume as
      compared with the preoperative one at GKS was 31%. Mean marginal dose was 12 Gy
      (11-12). Mean follow-up after GKS was 34.4 months (6-84). Conclusion  Our data
      show excellent results in large VS management with a combined approach of
      microsurgical subtotal resection and GKS on the residual tumor, with regard to
      the functional outcome and tumor control. Longer term follow-up is necessary to
      fully evaluate this approach, especially regarding tumor control.

PMID- 30210993
TI  - Usefulness of Preoperative Simulation in Skull Base Approach: A Case Report.
AB  - Skull base approach is a neurosurgical challenge requiring dexterity of the
      operating surgeon for good postoperative outcome. In addition to the experience
      of the operating surgeon, adequate preoperative information of the tumor is
      necessary to ensure better outcome. In clinoid meningioma, it is sometimes
      difficult to determine its relationship with the surrounding structure and the
      feeding artery. Previously, preoperative simulation has been utilized to
      determine the intracranial course of the compressed nerves in relation to the
      petroclival meningioma. We report a case of clinoid meningioma where preoperative
      fusion of three dimensional computed tomography angiography (3D-CTA) and 3T-fast
      imaging employing steady-state acquisition (FIESTA) images was useful in
      determining the exact location of the feeding artery to devascularize the tumor
      and aid in surgery. Preoperative simulation with three-dimensional digital
      subtraction angiography (3D-DSA) and 3T-FIESTA fusion images can be a useful
      adjunct tool to supplement surgery and to train neurosurgical trainees.

PMID- 30210994
TI  - Correlates of changes in walking during the retirement transition: The Multi
      Ethnic Study of Atherosclerosis.
AB  - Retirement from employment involves disruption in daily routines and has been
      associated with positive and negative changes in physical activity. Walking is
      the most common physical activity among older Americans. The factors that
      influence changes in walking after retirement are unknown. The study objective
      was to identify correlates of within-person change in recreational walking (for
      leisure) and transport walking (to get places) during the retirement transition
      among a multi-ethnic cohort of adults (N = 928) from six US communities.
      Correlates were measured at the individual (e.g., gender), interpersonal (e.g.,
      social support), and community (e.g., density of walking destinations) levels at
      study exams between 2000 and 2012. Comparing pre- and post-retirement measures
      (average 4.5 years apart), 50% of participants increased recreational walking by
      60 min or more per week, 31% decreased by 60 min or more per week, and 19%
      maintained their recreational walking. Forty-one percent of participants
      increased transport walking by 60 min or more per week, 40% decreased by 60 min
      or more per week, and 19% maintained their transport walking after retirement.
      Correlates differed for recreational and transport walking and for increases
      compared to decreases in walking. Self-rated health, chronic conditions, and
      perceptions of the neighborhood walking environment were associated with changes
      in both types of walking after retirement. Further, some correlates differed by
      gender and retirement age. Findings can inform the targeting of interventions to
      promote walking during the retirement transition.

PMID- 30210995
TI  - Does modified Otago Exercise Program improves balance in older people? A
      systematic review.
AB  - Exercise interventions focused on strength and balance are effective for falls
      prevention in older people, however compliance to exercise is often a problem.
      Tailored intervention programs are recommended to meet the person preferences and
      increase compliance. Otago Exercise Program (OEP) is the most disseminated fall
      prevention program and is individually prescribed at home. The purpose of this
      study was to identify OEP modified formats and investigate their effects on
      balance when compared to its original form of delivering. Four electronic
      databases were searched, PubMed, PEDro, Science Direct and Scopus, between
      January and February 2017. Eligibility criteria included experimental or
      qualitative design studies conducted among older adults (>=50 years) at risk of
      falling, ongoing exercise interventions with modified formats of OEP. The primary
      outcome was balance. The Preferred Reporting Items for Systematic Reviews and
      Meta-Analyses guidelines were used. Eight studies met the inclusion criteria,
      five were randomized controlled trials (RCTs), two were quasi-experimental and
      one was a qualitative study. Therefore, a qualitative analysis was performed.
      Modified formats of OEP included additional vestibular or multisensory balance
      exercises, augmented reality, exercise in group and a DVD delivering format (in
      group or individual). In general, all studies using OEP modified formats reported
      improvements on balance and functional ability. However, it remains unclear if it
      is as effective as the original OEP and which modified format is more effective.

PMID- 30210997
TI  - Corrigendum to "Impact of new rapid transit on physical activity: A meta
      analysis" Preventive Medicine Reports 10 (2018) 184-190.
AB  - [This corrects the article DOI: 10.1016/j.pmedr.2018.03.008.].

PMID- 30210996
TI  - Health behavior practice among understudied Chinese and Filipino Americans with
      cardiometabolic diseases.
AB  - Lifestyle modification and health behavior practice among the individuals with
      cardiometabolic diseases (CMD) are important for secondary prevention and disease
      control. This study was designed to investigate and compare health behavior
      practices among Chinese and Filipino Americans with CMD. Three hundred seventy
      four Asian Americans (211 Chinese and 163 Filipino) who reside in the greater
      Philadelphia region and had either CMD or no identified disease were included in
      the study. Information on smoking, alcohol intake, physical activity, and salt
      and sweets consumption was collected, as well as demographic and acculturative
      characteristics. Of the 374 participants, 241 (64.4%) had CMD and 133 (35.6%) had
      no identified disease. The majority of Chinese and Filipino Americans with CMD
      failed to meet the dietary and physical activity guidelines, and only a small
      percentage of them restricted their amount of salt added to food and amount of
      sweets consumption. Compared to participants with no disease, Chinese
      participants with CMD were more likely to "never" add salt to food (AOR 4.42
      compared to "frequently"). Filipino Americans with CMD were less likely to be
      those who "never" consume sweets than those who frequently consume sweets (AOR =
      0.12). Among the participants with CMD, Chinese participants with CMD were less
      likely to restrict drinking (AOR 0.11) than Filipinos with CMD. The findings
      suggest that tailored interventions for Chinese and Filipino Americans with CMD
      should be developed to enhance their compliance to behavioral guidelines to
      prevent further disease progression and complications.

PMID- 30210998
TI  - Objectively measured active travel and uses of activity-friendly neighborhood
      resources: Does change in use relate to change in physical activity and BMI?
AB  - Few studies examine how objectively measured use of local physical activity
      resources contributes to objectively-measured healthy physical activity and
      weight changes over time. We utilized objective measures to test whether changes
      in active travel and uses of three physical activity (PA) resources-parks,
      recreation centers, and transit- related to changes in PA and BMI. Adults (n =
      536) in Salt Lake City, UT, wore accelerometer and GPS units in 2012 and 2013,
      before and after neighborhood rail completion. Regression outcomes included
      accelerometer counts per minute (cpm), MVPA (moderate-to-vigorous activity
      minutes/10 h accelerometer wear) and measured BMI; key predictors were changes in
      active travel and PA resource uses (former and new uses). Significant results
      (all p < 0.05) showed that increased active travel related to increased total PA
      (59.86 cpm and 8.50 MVPA); decreased active travel related to decreased MVPA (-
      3.01 MVPA). Poorer outcomes were seen after discontinuing use of parks (- 36.29
      cpm, - 5.73 MVPA, and + 0.44 BMI points), recreation centers (- 6.18 MVPA), and
      transit (- 48.14 cpm, - 5.43 MVPA, and + 0.66 BMI). Healthier outcomes were seen
      after commencing use of parks (29.83 cpm, 5.25 MVPA), recreation centers (44.63
      cpm) and transit (38.44 cpm, 4.17 MVPA, and - 0.56 BMI). Transit and
      park/recreational center uses were unrelated, although park users were more
      likely to be recreation center users. Active travel and use of three neighborhood
      PA resources relate to healthy activity and could be fostered by policy and
      design.

PMID- 30211000
TI  - A case report on management of severe childhood pneumonia in low resource
      settings.
AB  - Pneumonia is a major cause of child mortality among children under five years,
      worldwide. Pneumonia infection may be caused by bacteria, viruses, or fungi in
      single or in both lungs. According to recent criteria developed by World Health
      Organization (WHO) in September (2013), pneumonia can be classified into severe
      pneumonia, pneumonia and no pneumonia. Most of the deaths occur from severe
      pneumonia and management of severe childhood pneumonia requires early
      identification, prompt referral and the availability of intensive quality of
      care. This case study aimed to represent the actual scenario of severe childhood
      pneumonia case management at community clinic. Considering that circumstances,
      International Centre for Diarrheal Disease Research, Bangladesh (icddr,b)
      developed an innovative day care management approach as safe, effective and less
      expensive alternative to hospital management of severe childhood pneumonia. A
      twenty-seven months old boy came to the Health & Family Welfare Centre (HFWC)
      with severe breathing difficulty, cough, history of fever. The management
      described below was continued daily until there was clinical improvement; no
      fever, no fast breathing, no lower chest wall indrawing, no danger signs, no
      rales on auscultation and no hypoxemia. Considering the WHO case management
      protocol for severe pneumonia, day care management approach on community clinic
      recommends that diagnosis of severe pneumonia should be based primarily on
      visible clinical parameters. On that basis, severe childhood pneumonia can be
      successfully managed at community clinics including for children with hypoxemia
      who is required prolong (4-6 hours) oxygen therapy.

PMID- 30210999
TI  - Analysis of stromal mucin in oral epithelial dysplasia & oral squamous cell
      carcinoma- A histochemical study.
AB  - Background: Mucins are glycoproteins that act as a selective molecular barrier
      and its alterations usually accompany the carcinogenesis. Aim: To evaluate the
      transition of mucins in the grades of oral epithelial dysplasia (OED) and oral
      squamous cell carcinoma (OSCC) using histochemical stains. Materials & Method: A
      total of 66 samples of variable grades of OED and OSCC and each section was
      stained with PAS, Alcian blue- PAS (AB-PAS) and Aldehyde fuschin - Alcian blue
      (AF-AB). Mucins pattern and intensity were examined at 5 randomly selected fields
      on 10x magnification. Results: 1. PAS stain - Predominantly OED and OSCC showed a
      diffuse pattern with a gradual decrease in intensity in OED and overall a weak
      intensity in OSCC. 2. AB-PAS stain - Neutral mucins showed gradual increase in
      its intensity in grades of OED and OSCC with no predominant pattern. The
      intensity for the acid mucins remains weak in all the grades of OED and OSCC with
      diffuse distribution, except in higher grades of OED and OSCC. 3. AF- AB stain -
      For sulphated mucins, in OED a focal and diffuse pattern was observed in OSCC
      with minimal intensity. The carboxylated mucin was absent in both. Conclusion:
      Mucins undergo change in its pattern and intensity in varying grades of OED/OSCC.
      Although in GIT and other mucosa, the expression of altered mucin is a recognized
      factor, seldom research has been done in OED and OSCC. Thus, the present study
      could be the stepping stone in the exploration of mucinous alteration in OED and
      OSCC.

PMID- 30211001
TI  - The effect of physical exercise on cerebral blood flow in Alzheimer's disease.
AB  - In recent years there has been an increasing focus on the relation between
      cerebrovascular health, physical exercise and Alzheimer's disease. The aim of the
      current study was to determine the effect of moderate-to-high-intensity aerobic
      exercise on cerebral blood flow in patients with mild to moderate Alzheimer's
      disease. Fifty-one patients were randomized to either usual care or moderate-to
      high intensity aerobic exercise for 16 weeks. Exercise had no consistent effect
      on whole brain or regional cerebral blood flow. Sixteen weeks of exercise are,
      therefore, not sufficient to produce a consistent increase in cerebral blood flow
      in a relatively small sample of Alzheimer's patients.

PMID- 30211002
TI  - Changes in cerebral activation in individuals with and without visual vertigo
      during optic flow: A functional near-infrared spectroscopy study.
AB  - Background and purpose: Individuals with visual vertigo (VV) describe symptoms of
      dizziness, disorientation, and/or impaired balance in environments with
      conflicting visual and vestibular information or complex visual stimuli. Physical
      therapists often prescribe habituation exercises using optic flow to treat these
      symptoms, but it is not known how individuals with VV process the visual stimuli.
      The primary purpose of this study was to use functional near-infrared
      spectroscopy (fNIRS) to determine if individuals with VV have different cerebral
      activation during optic flow compared with control subjects. Methods: Fifteen
      individuals (5 males and 10 females in each group) with VV seeking care for
      dizziness and 15 healthy controls (CON) stood in a virtual reality environment
      and viewed anterior-posterior optic flow. The support surface was either fixed or
      sway-referenced. Changes in cerebral activation were recorded using fNIRS during
      periods of optic flow relative to a stationary visual environment. Postural sway
      of the head and center of mass was recorded using an electromagnetic tracker.
      Results: Compared with CON, the VV group displayed decreased activation in the
      bilateral middle frontal regions when viewing optic flow while standing on a
      fixed platform. Despite both groups having significantly increased activation in
      most regions while viewing optic flow on a sway-referenced surface, the VV group
      did not have as much of an increase in the right middle frontal region when
      viewing unpredictable optic flow in comparison with the CON group. Discussion and
      conclusions: Individuals with VV produced a pattern of reduced middle frontal
      cerebral activation when viewing optic flow compared with CON. Decreased
      activation in the middle frontal regions of the cerebral cortex may represent an
      alteration in control over the normal reciprocal inhibitory visual-vestibular
      interaction in visually dependent individuals. Although preliminary, these
      findings add to a growing body of literature using functional brain imaging to
      explore changes in cerebral activation in individuals with complaints of
      dizziness, disorientation, and unsteadiness. Future studies in larger samples
      should explore if this decreased activation is modified following a
      rehabilitation regimen consisting of visual habituation exercises.

PMID- 30211004
TI  - Quantification of 11 enzyme activities of lysosomal storage disorders using
      liquid chromatography-tandem mass spectrometry.
AB  - Lysosomal storage disorders (LSDs) are characterized by the accumulation of
      lipids, glycolipids, oligosaccharides, mucopolysaccharides, and other biological
      substances because of the pathogenic deficiency of lysosomal enzymes. Such
      diseases are rare; thus, a multiplex assay for these disorders is effective for
      the identification of affected individuals during the presymptomatic period.
      Previous studies have demonstrated that such assays can be performed using liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) with multiple reaction
      monitoring (MRM) detection. An assay procedure to quantify the activity of 11
      enzymes associated with LSDs was provided. First, a validation study was
      performed using dried blood spot (DBS) samples with 100% and 5% enzyme activity
      for quality control (QC). Under the assay condition, the analytical range,
      defined as the ratio of the peak area of the enzyme reaction products from the
      DBS for QC with 100% enzyme activity to that from the filter paper blank sample,
      was between 14 for GALN and 4561 for GLA. Based on these results, the
      distribution of the enzyme activity for the 11 LSD enzymes was further examined.
      Consistent with the previous data, the enzyme activity exhibited a bell-shaped
      distribution with a single peak. The averaged enzyme activity for the healthy
      neonates was as follows: GLA, 3.80 +/- 1.6; GAA, 10.6 +/- 4.8; IDUA, 6.4 +/- 2.3;
      ABG, 8.6 +/- 3.1; ASM, 3.3 +/- 1.1; GALC, 2.8 +/- 1.3; ID2S, 16.7 +/- 6.1; GALN,
      1.2 +/- 0.5; ARSB, 17.0 +/- 8.7; NAGLU, 4.6 +/- 1.5; and GUSB, 46.6 +/- 19.0
      MUmol/h/L (mean +/- SD, n = 200). In contrast, the enzyme activity in disease
      affected individuals was lower than the minimum enzyme activity in healthy
      neonates. The results demonstrate that the population of disease-affected
      individuals was distinguished from that of healthy individuals by the use of LC
      MS/MS.

PMID- 30211005
TI  - Fabry disease. A potential pitfall A family with a novel intronic mutation.
AB  - Fabry disease is a genetic disorder characterized by the accumulation of
      globotriaosylceramide in cell lysosomes resulting from an X-linked deficiency of
      alpha-galactosidase A activity. It presents with multiorgan manifestations,
      including progressive renal disease, cardiomyopathy and premature demise.
      Recently, its prevalence has been reported to be higher in hemodialysis (HD)
      patients than in the general population. We report two cases of homozygous
      patients with an intronic alpha-galactosidase gene mutation and a classic
      phenotype of the disease. One of the patients had a kidney transplant and the
      donor was his brother, before Fabry disease were diagnose.

PMID- 30211003
TI  - Towards patient-specific modeling of brain tumor growth and formation of
      secondary nodes guided by DTI-MRI.
AB  - Previous studies to simulate brain tumor progression, often investigate either
      temporal changes in cancer cell density or the overall tissue-level growth of the
      tumor mass. Here, we developed a computational model to bridge these two
      approaches. The model incorporates the tumor biomechanical response at the tissue
      level and accounts for cellular events by modeling cancer cell proliferation,
      infiltration to surrounding tissues, and invasion to distant locations. Moreover,
      acquisition of high resolution human data from anatomical magnetic resonance
      imaging, diffusion tensor imaging and perfusion imaging was employed within the
      simulations towards a realistic and patient specific model. The model predicted
      the intratumoral mechanical stresses to range from 20 to 34 kPa, which caused an
      up to 4.5 mm displacement to the adjacent healthy tissue. Furthermore, the model
      predicted plausible cancer cell invasion patterns within the brain along the
      white matter fiber tracts. Finally, by varying the tumor vascular density and its
      invasive outer ring thickness, our model showed the potential of these parameters
      for guiding the timing (83-90 days) of cancer cell distant invasion as well as
      the number (0-2 sites) and location (temportal and/or parietal lobe) of the
      invasion sites.

PMID- 30211006
TI  - Epidermoid cyst on frenulum of the penis: A case report.
AB  - Epidermoid cyst in the penis is uncommon and only a small number of cases have
      been reported. We presented a thirty-two-year-old male patient with a case of
      slow growing, mobilized, non-tender frenulum of the penis mass that developed in
      10 years period. Surgery treatment was taken under local anesthesia. Pathological
      examination was revealed as epidermoid cyst. Care must be given during
      examination of these lesions to rule out another entity. If there is any
      indication, complete excision is the best treatment as another treatment may lead
      to the risk of recurrence.

PMID- 30211007
TI  - Fatty tumors of the retroperitoneum: Lipoma or well-differentiated liposarcoma.
      About a case of a giant retroperitoneal liposarcoma.

PMID- 30211008
TI  - Testicular non-seminomatous germ cell tumors (NSGCT) and brain metastases: About
      a rare location of the posterior fossa.

PMID- 30211010
TI  - Isolated brain metastasis of prostate carcinoma in the setting of normal prostate
      specific antigen.

PMID- 30211009
TI  - Single-system orthotopic ureterocele with calculus masquerading as a bladder
      tumour - A case report and review of literature.

PMID- 30211011
TI  - Prostatosymphyseal fistula after transurethral resection of the prostate (TURP),
      a rare and difficult to recognize complication.

PMID- 30211012
TI  - SDS-PAGE technique as biomarker for fish toxicological studies.
AB  - Although many studies on the hematological and biochemical parameters in fishes
      have been done, still there are some shortage in the estimation and evaluation of
      the baseline's values of marine and freshwater fishes. Recently, the use of
      hematology and biochemistry of fishes in toxicology, aquaculture, environmental
      pollution, feeding, and antioxidants studies has been increased. In this study we
      introduced the importance of those parameters and their importance as biomarkers
      in fish toxicology from previous literature and as new findings. Hemato
      biochemical parameters were widely used in fish toxicological studies. Many
      researches have used the protein electrophoresis as a valid tool to determining
      intra and inter-specific variation among species. Protein profile was extensively
      used in determining the health of fish, as indicators of anemia or other diseases
      provide information about the existence of the disease, and in the diagnosis of
      disease. So, to carry out the aim of this study, we reported one of the more
      advanced techniques used SDS-PAGE as molecular biomarker for protein profile
      analysis in fish with shedding the light on the importance of hematological and
      biochemical parameters in fish toxicological studies.

PMID- 30211013
TI  - Characterization and cytotoxic effect of biogenic silver nanoparticles on mitotic
      chromosomes of Drimia polyantha (Blatt. & McCann) Stearn.
AB  - Noble metal nanoparticles afford a tool for investigation and its application in
      biological systems has had the greatest impact in biology and biomedicine. The
      present work reports an ecofriendly approach for the synthesis of silver
      nanoparticles (AgNPs) using an aqueous leaf extract of Getonia floribunda. The
      silver nanoparticles were characterized by using following instruments viz. UV
      vis spectrophotometer, FTIR, XRD AFM and HR-TEM. The UV-vis spectrum showed a
      characteristic absorption peak at 404 nm. FTIR data reveals the possible
      involvement of various functional groups for reduction and biocapping of AgNPs.
      XRD data confirmed the crystalline nature of silver nanoparticles. Morphology,
      size and distribution of the AgNPs were determined by using AFM and HR-TEM. The
      average size of AgNPs ranges between 10 and 25 nm and are spherical in shape. The
      silver nanoparticles were evaluated for their cytotoxic effect on mitotic
      chromosomes of root meristematic cells of D. polyantha using different
      concentrations viz. 4, 8, 12 and 16 MUg/ml at the time interval of 6, 12, 18 and
      24 h. It is evident from the results that the higher concentration of AgNPs found
      to inhibit mitotic index and caused chromosomal abnormalities such as chromosomal
      bridge, sticky chromosomes, laggard anaphase, diagonal anaphase, c-metaphase and
      chromosomal breaks. Therefore, it can be concluded that higher concentrations of
      silver nanoparticles may induce significant inhibition of root meristem activity
      and causing DNA damage.

PMID- 30211014
TI  - Method for the simplistic modelling of the acoustic footprint of the vessels in
      the shallow marine area.
AB  - The definitions of the 11th descriptor of the EU Marine Strategy Framework
      Directive (MSFD) "Underwater noise and other forms of energy" outlines the
      standards for the continuous noise evaluation and monitoring in the European
      seas. Long lasting fluctuations of the continuous underwater noise at the shallow
      marine areas in the low frequency bands (<1 kHz) are mostly associated with the
      shipping noise, where these fluctuations are sensitive to changes in the spatial
      distribution of human activities, or changes of environmental and climatic
      variables. Underwater noise modelling is usually considered as a supplement to
      noise measurements, where models increases the utility of the measurement
      results. Noise mapping is considered as a form of spatial modelling, providing a
      convenient and accessible way to visualise models. Therefore, underwater noise
      models and maps can be used in management and evaluation of environmental state.
      There are number of freely available widely used noise source and sound
      propagation models. Still the simplistic logarithmic rules purposed for the sound
      propagation loss computations do not account for the number of factors in the
      marine environment, i.e. sediment type, water depth or frequency. On the other
      hand the sophisticated physical models purposed for the description of the
      footprint of noise sources such as ships are complex and their programing
      requires very specific knowledge. In this paper the details of the method
      purposed for modelling of the ship noise footprint in shallow seas is presented.
      Proposed method allows to compute: *depth dependent ship sound transmission
      losses in 1 Hz frequency bands;*sound propagation losses during different seasons
      (summer/winter);*acoustic footprint accounting for vessel noise directivity.

PMID- 30211015
TI  - Cleaning and sampling protocol for analysis of mercury and dissolved organic
      matter in freshwater systems.
AB  - Mercury (Hg), and in particular its methylated form (methylmercury, MeHg), is a
      hazardous substance with the potential to produce significant adverse
      neurological and other health effects. Enhanced anthropogenic emissions and long
      range transport of atmospheric Hg have increased Hg concentrations above
      background levels in aquatic systems. In this context, the Minamata Convention, a
      global legally binding agreement that seeks to prevent human exposure to Hg, was
      signed and enforced by 128 countries, and today more than 90 Parties have
      ratified it. All these Parties have committed to develop Hg monitoring programs
      to report the effectiveness of the convention. For this purpose, we provide a
      standardized cleaning and water sampling protocol for the determination of total
      Hg and MeHg in freshwaters at ambient levels. As Hg and organic matter are
      tightly bound, the protocol also describes sample collection for dissolved
      organic carbon (DOC) concentration and characterization of dissolved organic
      matter (DOM) composition by fluorescence spectroscopy. This protocol is highly
      useful to non-experts without a prior background in Hg sampling and analysis, and
      can serve as a useful basis for national monitoring programs. Furthermore, this
      protocol should help increase quantitative inventories of DOC, inorganic-Hg (IHg)
      and MeHg concentrations and DOM composition in freshwater, which are severely
      lacking at a global scale. *Provides a standardized method to collect water
      samples for IHg, MeHg, DOC and DOM composition from freshwater ecosystems.

PMID- 30211016
TI  - Genome sequence of Rhizomucor pusillus FCH 5.7, a thermophilic zygomycete
      involved in plant biomass degradation harbouring putative GH9 endoglucanases.
AB  - We report here the annotated draft genome sequence of the thermophilic zygomycete
      Rhizomucor pusillus strain FCH 5.7, isolated from compost soil in Vietnam. The
      genome assembly contains 25.59 Mb with an overall GC content of 44.95%, and
      comprises 10,898 protein coding genes. Genes encoding putative cellulose-, xylan-
      and chitin-degrading proteins were identified, including two putative
      endoglucanases (EC 3.2.1.4) from glycoside hydrolase family 9, which have so far
      been mostly assigned to bacteria and plants.

PMID- 30211017
TI  - Stepwise extraction of high-value chemicals from Arthrospira (Spirulina) and an
      economic feasibility study.
AB  - Arthrospira (Spirulina) consists of diverse high-value chemicals, such as
      phycocyanin, lipids/total fatty acids (TFA), and polysaccharides, which have been
      used for food, cosmetic and pharmacological applications. This study compared
      various stepwise extraction processes for these high-value chemicals. Considering
      the yield and properties of extracts, the most suitable extraction order was
      phycocyanin, lipid/TFA and polysaccharides. The yield of the main product (food
      grade phycocyanin) was 8.66% of the biomass dry weight, whereas the yields of the
      subsequent lipid/TFA and polysaccharide coproducts were 3.55% and 0.72%,
      respectively. The economic analysis showed that producing phycocyanin alone was
      economically feasible, but producing coproducts (lipid/TFA and polysaccharides)
      was not. The production cost of phycocyanin was US$ 249.70 kg-1, which is an
      encouraging figure for large-scale production. Moreover, the phycocyanin content
      of Arthrospira materials utilized for extraction should not be lower than 15% of
      dry weight to ensure positive the net present value (NPV) of investment.

PMID- 30211018
TI  - Multiscale modeling of glioblastoma.

PMID- 30211019
TI  - Clinical characteristics and outcomes associated with nasal intermittent
      mandatory ventilation in acute pediatric respiratory failure.
AB  - AIM: To characterize the clinical course and outcomes of nasal intermittent
      mandatory ventilation (NIMV) use in acute pediatric respiratory failure. METHODS:
      We identified all patients treated with NIMV in the pediatric intensive care unit
      (PICU) or inpatient general pediatrics between January 2013 and December 2015 at
      two academic centers. Patients who utilized NIMV with other modes of noninvasive
      ventilation during the same admission were included. Data included demographics,
      vital signs on admission and prior to initiation of NIMV, pediatric risk of
      mortality III (PRISM-III) scores, complications, respiratory support
      characteristics, PICU and hospital length of stays, duration of respiratory
      support, and complications. Patients who did not require escalation to mechanical
      ventilation were defined as NIMV responders; those who required escalation to
      mechanical ventilation (MV) were defined as NIMV non-responders. NIMV responders
      were compared to NIMV non-responders. RESULTS: Forty-two patients met study
      criteria. Six (14%) failed treatment and required MV. The majority of the
      patients (74%) had a primary diagnosis of bronchiolitis. The median age of these
      42 patients was 4 mo (range 0.5-28.1 mo, IQR 7, P = 0.69). No significant
      difference was measured in other baseline demographics and vitals on initiation
      of NIMV; these included age, temperature, respiratory rate, O2 saturation, heart
      rate, systolic blood pressure, diastolic blood pressure, and PRISM-III scores.
      The duration of NIMV was shorter in the NIMV non-responder vs NIMV responder
      group (6.5 h vs 65 h, P < 0.0005). Otherwise, NIMV failure was not associated
      with significant differences in PICU length of stay (LOS), hospital LOS, or total
      duration of respiratory support. No patients had aspiration pneumonia,
      pneumothorax, or skin breakdown. CONCLUSION: Most of our patients responded to
      NIMV. NIMV failure is not associated with differences in hospital LOS, PICU LOS,
      or duration of respiratory support.

PMID- 30211020
TI  - Prognostic role of tumor budding in breast cancer.
AB  - Tumor budding, defined as a small number of cancer cells observed in pathology
      sections detached from the main tumor mass, is a common phenomenon in cancer. It
      is suggested that cells in buds are in the process of actively moving away from
      the primary tumor in the first step of metastasis. Tumor budding has been
      observed in a variety of carcinomas and is best studied in colorectal cancers
      where it portends poor prognosis. More recently, tumor budding was found to be of
      prognostic significance in other cancers including breast cancer. Tumor budding
      in breast cancer is associated with other adverse pathologic factors, such as
      larger tumor size and lymphovascular invasion, but may have additional
      independent prognostic value. In the future, standardization of the
      quantification criteria for tumor budding may further aid in its adoption as a
      prognostic marker.

PMID- 30211022
TI  - Early urological complications after kidney transplantation: An overview.
AB  - Urological complications, especially urine leaks, remain the most common type of
      surgical complication in the early post-transplant period. Despite major advances
      in the field of transplantation, a small minority of kidney transplants are still
      being lost due to urological problems. Many of these complications can be traced
      back to the time of retrieval and implantation. Serial ultrasound examination of
      the transplanted graft in the early post-operative period is of key importance
      for early detection. The prognosis is generally excellent if recognized and
      managed in a timely fashion. The purpose of this narrative review is to discuss
      the different presentations, compare various ureterovesical anastomosis
      techniques and provide a basic overview for the management of post-transplant
      urological complications.

PMID- 30211023
TI  - Introduction of everolimus in kidney transplant recipients at a late
      posttransplant stage.
AB  - This minireview focuses on the current knowledge about the introduction of
      everolimus (EVL), a mammalian target of rapamycin inhibitor, with calcineurin
      inhibitor (CNI) elimination or minimization in kidney transplant recipients at a
      late posttransplant stage. Within, we have summarized two major clinical trials,
      ASCERTAIN and APOLLO, and seven other retrospective or nonrandomized studies. In
      the open-label multicenter ASCERTAIN study, the estimated glomerular filtration
      rate (eGFR) at 24 mo after conversion was not significantly different between
      three groups-EVL with CNI elimination, CNI minimization and continued CNI
      unchanged-at a mean of 5.4 years after transplantation. However, recipients with
      baseline creatinine clearance higher than 50 mL/min had a greater increase in
      measured GFR after CNI elimination. In the open-label multicenter APOLLO study,
      adjusted eGFR within the on-treatment population was significantly higher in the
      EVL continuation group than in the CNI continuation group at 12 mo after
      conversion at a mean of 7 years posttransplantation. Other studies on recipients
      without adverse events and already having satisfactory renal function showed
      favorable graft function by EVL late-induction with CNI elimination or reduction.
      These studies showed that chronic allograft nephropathy, CNI nephrotoxicity, CNI
      arteriolopathy, cancer and viral infection (especially cytomegalovirus infection)
      may be good indications for late conversion to EVL.

PMID- 30211024
TI  - Interaction of immunosuppressants with HCV antivirals daclatasvir and
      asunaprevir: combined effects with mycophenolic acid.
AB  - AIM: To investigate the specific effects of immunosuppressants on the antiviral
      action of daclatasvir and asunaprevir. METHODS: The antiviral activity of
      daclatasvir (DCV) and asunaprevir (ASV) combined with immunosuppressants was
      tested using two in vitro models for hepatitis C virus (HCV) infection. RESULTS:
      Tacrolimus, rapamycin and cyclosporine did not negatively affect the antiviral
      action of DCV or ASV. Mycophenolic acid (MPA) showed additive antiviral effects
      combined with these direct acting antivirals (DAAs). MPA induces interferon
      stimulated genes (ISGs) and is a potent GTP synthesis inhibitor. DCV or ASV did
      not induce ISGs expression nor affected ISG induction by MPA. Rather, the
      combined antiviral effect of MPA with DCV and ASV was partly mediated via
      inhibition of GTP synthesis. CONCLUSION: Immunosuppressants do not negatively
      affect the antiviral activity of DAAs. MPA has additive effect on the antiviral
      action of DCV and ASV. This combined benefit needs to be confirmed in prospective
      clinical trials.

PMID- 30211025
TI  - Trends of characteristics and outcomes of donors and recipients of deceased donor
      liver transplantation in the United States: 1990 to 2013.
AB  - AIM: To compare trends in donor/recipient characteristics and outcomes using four
      period cohorts of liver transplant recipients from 1990 to 2009. METHODS: Seventy
      thousand three hundred and seventy-seven adult first-time recipients of whole
      organ deceased-donor liver grafts from 1990 to 2009 were followed up until
      September 2013. Four periods based on transplantation dates were considered to
      account for developments in transplantation. Descriptive statistics were used to
      describe donor/recipient characteristics and transplant outcomes. Statistical
      comparisons between periods were performed using chi2/Fischer's exact test
      (categorical variables) and t-tests/Mann-Whitney U test (continuous variables).
      Univariate descriptive statistics/survival data were generated using Kaplan-Meier
      curves. Cox Proportional Hazards models were used for regression analyses of
      patient and graft survival. RESULTS: Mean age (years), body mass index (kg/m2),
      and the proportion of males were, respectively, 39.1 (+/- 17.4), 25.9 (+/- 5.7)
      and 60.3 for donors, and 51.3 (+/- 10.5), 27.7 (+/- 5.6), and 64.4 for
      recipients. Donor and transplantation rates differed between racial/ethnic
      groups. Median (Q1-Q3) cold and warm ischemia, waitlist, and hospital stay times
      were 8 (6.0-10.0) h and 45 (35-59) min, 93 (21-278) d, and 12 (8-20) d. Total
      functional assistance was required by 8% of recipients at wait-listing and 13.4%
      at transplantation. Overall survival at 1, 3, 5, 10, 15, and 20 years was 87.3%,
      79.4%, 73.6%, 59.8%, 46.7%, and 35.9%, respectively. The 2005-2009 cohort had
      better patient and graft survival than the 1990-1994 cohort overall [HR 0.67
      (0.62-0.72) and 0.66 (0.62-0.71)] and at five years [HR 0.73 (0.66-0.80) and 0.71
      (0.65-0.77)]. CONCLUSION: Despite changes in donor quality, recipient
      characteristics, and declining functional status among transplant recipients,
      overall patient survival is superior and post-transplant outcomes continue to
      improve.

PMID- 30211021
TI  - Thrombotic microangiopathy after renal transplantation: Current insights in de
      novo and recurrent disease.
AB  - Thrombotic microangiopathy (TMA) is one of the most devastating sequalae of
      kidney transplantation. A number of published articles have covered either de
      novo or recurrent TMA in an isolated manner. We have, hereby, in this article
      endeavored to address both types of TMA in a comparative mode. We appreciate that
      de novo TMA is more common and its prognosis is poorer than recurrent TMA; the
      latter has a genetic background, with mutations that impact disease behavior and,
      consequently, allograft and patient survival. Post-transplant TMA can occur as a
      recurrence of the disease involving the native kidney or as de novo disease with
      no evidence of previous involvement before transplant. While atypical hemolytic
      uremic syndrome is a rare disease that results from complement dysregulation with
      alternative pathway overactivity, de novo TMA is a heterogenous set of various
      etiologies and constitutes the vast majority of post-transplant TMA cases.
      Management of both diseases varies from simple maneuvers, e.g., plasmapheresis,
      drug withdrawal or dose modification, to lifelong complement blockade, which is
      rather costly. Careful donor selection and proper recipient preparation,
      including complete genetic screening, would be a pragmatic approach. Novel
      therapies, e.g., purified products of the deficient genes, though promising in
      theory, are not yet of proven value.

PMID- 30211026
TI  - Treatment with plasmapheresis, immunoglobulins and rituximab for chronic-active
      antibody-mediated rejection in kidney transplantation: Clinical, immunological
      and pathological results.
AB  - AIM: To evaluate the role of a therapeutic regimen with plasma exchange,
      intravenous immunoglobulins and rituximab in chronic-active antibody-mediated
      rejection (cAMR) settings. METHODS: We compared 21 kidney transplant recipients
      (KTRs) with a diagnosis of cAMR in a retrospective case-control analysis: nine
      KTRs treated with plasmapheresis, intravenous immunoglobulins and rituximab (PE
      IVIG-RTX group) vs 12 patients (control group) not treated with antibody-targeted
      therapies. We examined kidney survival and functional outcomes 24 mo after
      diagnosis. Histological features and donor-specific antibody (DSA)
      characteristics (MFI and C1q-fixing ability) were also investigated. RESULTS: No
      difference in graft survival between the two groups was noted: three out of nine
      patients in the PE-IVIG-RTX group (33.3%) and 4/12 in the control group (33.3%)
      experienced loss of allograft function at a median time after diagnosis of 14 mo
      (min 12-max 18) and 15 mo (min 7-max 22), respectively. Kidney functional tests
      and proteinuria 24 mo after cAMR diagnosis were also similar in both groups. Only
      microvascular inflammation (glomerulitis + peritubular capillaritis score) was
      significantly reduced after PE-IVIG-RTX in seven out of eight patients (87.5%) in
      the PE-IVIG-RTX group (median score 3 in pre-treatment biopsy vs 1.5 in post
      treatment biopsy; P = 0.047), without any impact on kidney survival and/or DSA
      characteristics. No functional or histological parameter at diagnosis was
      predictive of clinical outcome. CONCLUSION: Our data showed no difference in the
      two year post-treatment outcome of kidney grafts treated with PE-IVIG-RTX for
      cAMR diagnosis, however there were notable improvements in microvascular
      inflammation in post-therapy protocol biopsies. Further studies, especially
      involving innovative therapeutic approaches, are required to improve the
      management and long-term results of this severe condition.

PMID- 30211027
TI  - Clinical features and determinants of VO2peak in de novo heart transplant
      recipients.
AB  - AIM: To study exercise capacity and determinants of early peak oxygen consumption
      (VO2peak) in a cohort of de novo heart transplant (HTx) recipients. METHODS: To
      determine possible central (chronotropic responses, cardiopulmonary and
      hemodynamic function) and peripheral factors (muscular exercise capacity and body
      composition) predictive of VO2peak, a number of different measurements and tests
      were performed, as follows: Cardiopulmonary exercise testing (CPET) was performed
      mean 11 wk after surgery in 81 HTx recipients > 18 years and was measured with
      breath by breath gas exchange on a treadmill or bicycle ergometer.
      Metabolic/respiratory measures include VO2peak and VE/VCO2 slope. Additional
      measures included muscle strength testing, bioelectrical impedance analysis,
      echocardiography, blood sampling and health-related quality of life. Based on the
      VO2peak (mL/kg per minute) median value, the study population was divided into
      two groups defined as a low-capacity group and a high-capacity group. Potential
      predictors were analyzed using multiple regression analysis with VO2peak (L/min)
      as the dependent variable. RESULTS: The mean +/- standard deviation (SD) age of
      the total study population was 49 +/- 13 years, and 73% were men. This de novo
      HTx cohort demonstrated a median VO2peak level of 19.4 mL/kg per min at 11 +/-
      1.8 wk post-HTx. As compared with the high-capacity group, the low-capacity group
      exercised for a shorter time, had lower maximal ventilation, O2 pulse, peak heart
      rate and heart rate reserve, while the VE/VCO2 slope was higher. The low-capacity
      group had less muscle strength and muscular exercise capacity in comparison with
      the high-capacity group. In order of importance, O2 pulse, heart rate reserve,
      muscular exercise capacity, body mass index, gender and age accounted for 84% of
      the variance in VO2peak (L/min). There were no minor or major serious adverse
      events during the CPET. CONCLUSION: Although there is great individual variance
      among de novo HTx recipients, early VO2peak measures appear to be influenced by
      both central and peripheral factors.

PMID- 30211028
TI  - A small molecule fibrokinase inhibitor in a model of fibropolycystic hepatorenal
      disease.
AB  - AIM: To evaluate the novel platelet-derived growth factor receptor and vascular
      endothelial growth factor receptor dual kinase inhibitor ANG3070 in a polycystic
      kidney disease-congenital hepatic fibrosis model. METHODS: At 6 wk of age, PCK
      rats were randomized to vehicle or ANG3070 for 4 wk. At 10 wk, 24 h urine and
      left kidneys were collected and rats were continued on treatment for 4 wk. At 14
      wk, 24 h urine was collected, rats were sacrificed, and liver and right kidneys
      were collected for histological evaluation. For Western blot studies, PCK rats
      were treated with vehicle or ANG3070 for 7 d and sacrificed approximately 30 min
      after the last treatments. RESULTS: Compared to the wild-type cohort, the PCK
      kidney (Vehicle cohort) exhibited a marked increase in kidney and liver mass,
      hepato-renal cystic volume, hepato-renal fibrosis and hepato-renal injury
      biomarkers. Intervention with ANG3070 in PCK rats decreased kidney weight,
      reduced renal cystic volume and reduced total kidney hydroxyproline, indicating
      significantly reduced rental interstitial fibrosis compared to the PCK-Vehicle
      cohort. ANG3070 treatment also mitigated several markers of kidney injury,
      including urinary neutrophil gelatinase-associated lipocalin, kidney injury
      molecule-1, cystatin C and interleukin-18 levels. In addition, this treatment
      attenuated key indices of renal dysfunction, including proteinuria, albuminuria
      and serum blood urea nitrogen and creatinine, and significantly improved renal
      function compared to the PCK-Vehicle cohort. ANG3070 treatment also significantly
      decreased liver enlargement, hepatic lesions, and liver fibrosis, and mitigated
      liver dysfunction compared to the PCK-Vehicle cohort. CONCLUSION: These results
      suggest that ANG3070 has the potential to slow disease, and may serve as a bridge
      toward hepato-renal transplantation in patients with fibropolycystic disease.

PMID- 30211029
TI  - Unique interstitial miRNA signature drives fibrosis in a murine model of
      autosomal dominant polycystic kidney disease.
AB  - AIM: To delineate changes in miRNA expression localized to the peri-cystic local
      microenvironment (PLM) in an orthologous mouse model of autosomal dominant
      polycystic kidney disease (ADPKD) (mcwPkd1(nl/nl) ). METHODS: We profiled miRNA
      expression in the whole kidney and laser captured microdissection (LCM) samples
      from PLM in mcwPkd1(nl/nl) kidneys with Qiagen miScript 384 HC miRNA PCR arrays.
      The three times points used are: (1) post-natal (PN) day 21, before the
      development of trichrome-positive areas; (2) PN28, the earliest sign of trichrome
      staining; and (3) PN42 following the development of progressive fibrosis. PN21
      served as appropriate controls and as the reference time point for comparison of
      miRNA expression profiles. RESULTS: LCM samples revealed three temporally
      upregulated miRNAs [2 to 2.75-fold at PN28 and 2.5 to 4-fold (P <= 0.05) at PN42]
      and four temporally downregulated miRNAs [2 to 2.75 fold at PN28 and 2.75 to 5
      fold (P <= 0.05) at PN42]. Expression of twenty-six miRNAs showed no change until
      PN42 [six decreased (2.25 to 3.5-fold) (P <= 0.05) and 20 increased (2 to 4-fold)
      (P <= 0.05)]. Many critical miRNA changes seen in the LCM samples from PLM were
      not seen in the contralateral whole kidney. CONCLUSION: Precise sampling with LCM
      identifies miRNA changes that occur with the initiation and progression of renal
      interstitial fibrosis (RIF). Identification of the target proteins regulated by
      these miRNAs will provide new insight into the process of fibrosis and identify
      unique therapeutic targets to prevent or slow the development and progression of
      RIF in ADPKD.

PMID- 30211030
TI  - Cardiac balanced steady-state free precession MRI at 0.35 T: a comparison study
      with 1.5 T.
AB  - Background: While low-field MRI is disadvantaged by a reduced signal-to-noise
      ratio (SNR) compared to higher fields, it has a number of useful features such as
      decreased SAR and shorter T1, and has shown promise for diagnostic imaging. This
      study demonstrates the feasibility of cardiac balanced steady-state free
      precession (bSSFP) MRI at 0.35 T and compares cardiac bSSFP MRI images at 0.35 T
      with those at 1.5 T. Methods: Cardiac images were acquired in 7 healthy
      volunteers using an ECG-gated bSSFP cine sequence on a 0.35 T superconducting MR
      system as well as a clinical 1.5 T system. Blood and myocardium SNR and contrast
      to-noise ratio (CNR) were computed. Subjective image scoring was used to compare
      the image quality between 0.35 and 1.5 T. Results: Cardiac images at 0.35 T were
      successfully acquired in all volunteers. While the 0.35 T images were noisier
      than those at 1.5 T, blood, myocardium and papillary muscles could be clearly
      delineated. At 0.35 T, bSSFP images were acquired at flip angles as high as 150
      degrees . Maximum CNR was achieved at 130 degrees . Image quality scoring showed
      that while at lower flip angles, the 0.35 T images had poorer quality than the
      1.5 T, but with flip angles of 110 and 130, the image quality at 0.35 T had
      scores similar to those at 1.5 T. Conclusions: This study demonstrates that
      cardiac bSSFP imaging is highly feasible at 0.35 T.

PMID- 30211031
TI  - Analysis of geometric variation of neck node levels during image-guided
      radiotherapy for nasopharyngeal carcinoma: recommended planning margins.
AB  - Background: To quantify the geometrical changes of each neck nodal level (NNL)
      and estimate the geometric planning target volume (PTV) margin during image
      guided radiotherapy (IGRT) for nasopharyngeal cancer (NPC). Methods: Twenty
      patients with locally advanced NPC underwent one planning computed tomography
      (CTplan) and 6 weekly repeat CT (CTrep) scans during chemoradiotherapy. Each
      CTrep was rigidly registered to the CTplan. All the NNLs were manually delineated
      in each transverse CT section. When comparing the NNL in CTrep with CTplan, their
      volumes, displacement of the center of the mass, and the shortest perpendicular
      distance (SPD) were automatically calculated. This was followed by calculation of
      the systematic and random errors, overlapping index (OI), and dice similarity
      coefficient (DSC). With PTVs isotropically expanded from NNL by 1, 2, 3, 4, and 5
      mm, they were compared with NNL itself; OI >0.95 was defined as the acceptable
      geometrical coverage. The Mann-Whitney test was used for statistical analysis.
      Results: All volumes, OI, and DSC of the NNLs (not including level IA) showed a
      linear decrease over time throughout the treatment course. The volume of NNLs
      decreased by 1-6% in the first week and 10-21% in the sixth week. The mean SPD
      was 1.3-1.7 and 1.9-3.5 mm in the first and sixth week respectively. The DSCs for
      nodal level IB, II, III, and IV were >0.7 and that of level V was <0.7 throughout
      the treatment course. For level IA and VI, DSC was <0.7 after the 2nd week. To
      maintain the OI >0.95, 2-5 mm was needed to expand the different NNLs.
      Conclusions: The geometrical changes of each NNL are substantial and the
      necessary margin of 2-5 mm depended on individual NNL is needed to maintain
      geometrical coverage throughout the course of IGRT for NPC.

PMID- 30211032
TI  - Improved image quality of low-dose CT combining with iterative model
      reconstruction algorithm for response assessment in patients after treatment of
      malignant tumor.
AB  - Background: To evaluate the image quality and radiation dose of low-dose (LD)
      computed tomography (LD-CT) combining with iterative model reconstruction (IMR)
      algorithm for response assessment in patients after treatment of malignant tumor
      compared with routine-dose CT (RD-CT). Methods: Forty-seven patients [mean age
      57.8+/-10.9 years, 30 males, body mass index (BMI) 22.09+/-2.35 kg/m2] after
      treatment of malignant tumor underwent contrast-enhanced chest and abdomen CT
      twice for response assessment with an interval of 6 months according to clinical
      routine. The first CT scans were performed with RD protocol at 120 kVp and images
      were reconstructed with filtered back projection (FBP) algorithm; while the
      second scans were performed with LD protocol at 100 kVp and images were
      reconstructed with FBP and IMR algorithm respectively. All scans were performed
      using an automatic tube current modulation technique with 150 mAs as reference.
      Objective image quality including CT attenuation, image noise, and contrast to
      noise ratio (CNR), and subjective image quality including artifacts, noise,
      visualization of small structures and confidence of targeted lesions, as well as
      lesion detection were assessed and compared. Results: Effective radiation dose of
      LD-CT scans was reduced 54.8% compared to RD-CT scans (26.89+/-3.35 vs. 12.14+/
      2.09 mSv). Higher CT attenuation was found in both LD-IMR and LD-FBP images
      compared to RD-FBP images. Better subjective image quality and CNR as well as
      lower objective noise were found in LD-IMR images (all, P<0.05). Two small
      lesions with the diameter less than 1 cm were missed in LD-FBP images, which were
      able to be observed in LD-IMR images. Conclusions: IMR is able to help more than
      half of reduction of radiation dose without compromising the quality of
      diagnostic information in patients after treatment of malignant tumors to chest
      and abdomen CT for response assessment.

PMID- 30211033
TI  - Accurate estimation of choriocapillaris flow deficits beyond normal
      intercapillary spacing with swept source OCT angiography.
AB  - Background: To estimate choriocapillaris flow deficits beyond normal
      intercapillary distance with swept source optical coherence tomography
      angiography (SS-OCTA). Methods: Subjects were enrolled and repeated SS-OCTA scans
      were performed using the 3 mm * 3 mm scan pattern. Blood flow was identified
      using the complex optical microangiography (OMAGc) algorithm. The
      choriocapillaris (CC) was defined as a 20 um slab of the flow volume beneath the
      outer boundary of Bruch's membrane (BM) and was compensated with the
      corresponding structural image for flow deficits measurement. Flow deficits were
      segmented based on one mean standard deviation from a normal database. A
      histogram based thresholding method was developed to remove small flow deficits
      that were determined by examining intercapillary spacing within normal CC
      networks. A registration method based on affine and B-spline transformation was
      utilized for the CC angiogram averaging. Four repeated scans were averaged, and
      results were compared with and without removal of small flow deficits after
      averaging a different number of scans (N=1, group 1; N=2, group 2; N=3, group 3
      and N=4, group 4). Results: Seven normal subjects were enrolled. Intercapillary
      distance was found to be 24 um for the CC networks under OCTA, which was used as
      the threshold to exclude small flow deficits for CC quantification. After
      averaging, significant reduction in background noise and improvement in
      continuity of blood vessel networks were observed both on retinal and
      choriocapillaris angiograms. Flow deficit percentages of the choriocapillaris
      were significantly reduced with averaging (group 1 vs. group 2: P<0.0001; group 2
      vs. group 3: P<0.001; group 3 vs. group 4: P<0.001). The flow deficit percentages
      were also significantly reduced after removing the small flow deficits (<=24 um
      in diameter) in all groups (P<0.01). A statistically significant difference was
      found after removing small flow deficits (<=24 um in diameter) between group 1
      and group 2 (P<0.001), between group 2 and group 3 (P<0.05), and between group 3
      and group 4 (P<0.05). However, the significance was decreased compared to that
      without small flow deficits removal. Conclusions: A method was developed to
      improve the robust estimation of choriocapillaris flow deficits by removing the
      small flow deficits corresponding to normal intercapillary spacing. After the
      removal of small flow deficits, fewer repeats were required for image averaging
      to achieve comparable accuracy of flow deficit measurements with SS-OCTA.

PMID- 30211034
TI  - The protocol for the Prospective Urban Rural Epidemiology China Action on Spine
      and Hip status study.
AB  - The Prospective Urban Rural Epidemiology (PURE) China Action on Spine and Hip
      status (CASH) study focused on the prevalence of osteoporosis and spinal fracture
      in China. The aim of the PURE CASH study is to determine the prevalence of
      osteoporosis and spinal fracture, and explore the potential relationship between
      spinal fracture and bone mineral density (BMD). This study is a prospective large
      scale population study with a community-based sampling and recruitment strategy.
      The aim is to determine the prevalence of osteoporosis and vertebral fracture in
      this population, to evaluate the association between vertebral fractures and BMD
      values, and to assess the prediction power of BMD for incident fractures.
      Participants in the PURE CASH study are all from the PURE study in China,
      recruited from 12 centers in 7 Chinese provinces. The inclusion criteria are that
      participants should be aged more than 40 years and able to give informed consent.
      Exclusion criteria are pregnant women, individuals with metal implants in the
      lumbar spine, use of medications or the existence of any disease or condition
      known to have a major influence on BMD, and inability to give informed consent. A
      total of 3,457 participants undergo a quantitative computed tomography (QCT) scan
      of the upper abdomen. The scanning parameters are as follows: 120 kVp at all
      centers, mAs between 75 and 200, FOV 40 cm*40 cm. The BMD values of L1 to L3 are
      measured, and the average BMD calculated. The American College of Radiology QCT
      criteria for the diagnosis of osteoporosis is applied to determine the presence
      of osteoporosis. The scout view images of T4-L4 vertebrae are reviewed by two
      experienced radiologists for semi-quantification of vertebral fractures according
      to Genant's method.

PMID- 30211036
TI  - Biomineralized hybrid nanoparticles for imaging and therapy of cancers.
AB  - In this review, we describe the research trends of hybrid nanocarriers developed
      based on a biomimetic mineralization process, and their recent applications in
      imaging and therapy of cancers. Organic-inorganic hybrid nanostructures formed by
      diverse biomimetic mineralization approaches are briefly reviewed, and
      particularly, the biomedical applications of these hybrid nanocarriers for the
      diagnosis and therapy of cancers are discussed. Biomineralization is an important
      process in which living organisms produce biominerals, such as calcium phosphate
      (CaP), calcium carbonate (CaCO3), and silica (SiO2), to strengthen their tissues,
      as found in the formation of bone and teeth. Introducing the artificial
      biomimetic mineralization process to nanobiotechnology has inspired researchers
      to develop smart stimuli-responsive nanoparticles for multiple purposes, such as
      improved therapeutic activity and activatable imaging of cancers.

PMID- 30211035
TI  - Comprehensive genotype-phenotype correlation in lissencephaly.
AB  - Malformations of cortical development (MCD) are a heterogenous group of disorders
      with diverse genotypic and phenotypic variations. Lissencephaly is a subtype of
      MCD caused by defect in neuronal migration, which occurs between 12 and 24 weeks
      of gestation. The continuous advancement in the field of molecular genetics in
      the last decade has led to identification of at least 19 lissencephaly-related
      genes, most of which are related to microtubule structural proteins (tubulin) or
      microtubule-associated proteins (MAPs). The aim of this review article is to
      bring together current knowledge of gene mutations associated with lissencephaly
      and to provide a comprehensive genotype-phenotype correlation. Illustrative cases
      will be presented to facilitate the understanding of the described genotype
      phenotype correlation.

PMID- 30211037
TI  - The 8th lung cancer TNM classification and clinical staging system: review of the
      changes and clinical implications.
AB  - Lung cancer is the leading cause of cancer death in both men and women. Clinical
      staging plays a crucial role in predicting survivor as well as influencing
      management option in lung cancer patients. Guidelines are constantly being
      reviewed as more data becomes available to provide the most accurate prognostic
      markers, hence aiding in the clinical detection and staging of lung cancer. Since
      its introduction in the 1970s, the TNM staging has undergone significant
      revisions with the latest, 8th edition, being effective internationally from
      2018. This edition re-categorizes the tumour size and other non-quantitative
      tumour descriptors (T), and further subclassifies extra-thoracic metastases (M).
      The clinical nodal (N) classifier is unchanged as the earlier version correlates
      well with prognosis. The downstream effects on staging to accommodate for the new
      T and M classifications are highlighted. The survival is inversely proportional
      to every centimeter increase in tumour size up till 7 cm, where the same
      prognosis as a T4 disease is reached. Hence, some of the T-classifiers based on
      size of the tumour is upstaged to reflect that. Invasion of the diaphragm is
      considered T4 instead of T3. On the other hand, involvement of the main bronchus
      regardless of tumour distance to carina as well as atelectasis is down-staged
      from a T3 to a T2 disease. Since the 7th edition, new entities of lung tumour
      known as adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA)
      have been introduced. The T-defining features are also described in this
      manuscript. Extrathoracic metastases that were classified as M1b in the 7th
      edition is further subcategorized into M1b and M1c in the 8th edition, to better
      define oligometastasis which has a better prognosis, and may benefit from more
      aggressive local therapy. This overview aims to provide radiologists with a
      description of the changes in the latest edition including staging of subsolid
      and multiple nodules, outline potential limitations of this 8th edition, as well
      as discussion on the implications on treatment.

PMID- 30211038
TI  - The role of delta radiomics in gastric cancer.

PMID- 30211039
TI  - Deep infiltrating endometriosis: role of magnetic resonance subtraction imaging.

PMID- 30211040
TI  - Male genitourinary reconstruction and trauma.

PMID- 30211042
TI  - Role of androgens for urethral homeostasis.
AB  - Background: We observed that patients with hypogonadism are at higher risk to
      experience artificial urinary sphincter cuff erosion. Sphincter erosions have
      been found to be associated with urethral atrophy or compromised urethras
      subsequent to events limiting its blood supply. We therefore analyzed possible
      mechanisms how a decrease in testosterone serum levels can result decreased
      urethral blood flow. Methods: In a cohort of >1,200 urethroplasties, tissue
      specimens obtained during surgeries were analyzed for expression of androgen
      receptor (AR), AR-responsive TIE-2 associated with angiogenesis, and the
      endothelial cell marker CD31 for determination of vessel counts were analyzed
      immunohistochemically. A total of 11 patients were included in whom both tissue
      and serum testosterone levels within 2 years of the urethroplasty was available.
      Low serum testosterone level defined as <280 ng/dL. Image J software was used to
      analyze expression profiles. Results: Mean serum testosterone level was
      significant lower in hypogonadal patients (179.4 ng/dL) compared to eugonadal
      patients (375.0 ng/dL, P=0.003). Urethral tissue of hypogonadal patients showed
      decreased AR expression [1.11% high power field (HPF)] compared to eugonadal
      patients (1.62%, P=0.016), decreased TIE-2 expression (1.84% HPF vs. 3.08%,
      P=0.006), and also decreased vessel counts (44.47 vessels/HPF vs. 98.33,
      P=0.004). There was a direct correlation of AR and TIE-2 expression levels with
      serum testosterone levels (rho 0.685, P=0.029, and rho 0.773, P=0.005,
      respectively). Of note, we did not detect a difference in age, prior radiation,
      coronary artery disease or hypertension among hypo- or eugonadal patient.
      However, higher body mass index was associated with low serum testosterone
      levels. Conclusions: Hypogonadal status is associated with decreased expression
      of AR and TIE-2 and also reduced vessel count in urethral tissue. We believe that
      the resulting decreased urethral vascularity subsequent to a hypogonadal state
      may be an important risk factor for complications of urethral surgery.

PMID- 30211041
TI  - An American Association for the Surgery of Trauma (AAST) prospective multi-center
      research protocol: outcomes of urethral realignment versus suprapubic cystostomy
      after pelvic fracture urethral injury.
AB  - Background: Pelvic fracture urethral injuries (PFUI) occur in up to 10% of pelvic
      fractures. It remains controversial whether initial primary urethral realignment
      (PR) after PFUI decreases the incidence of urethral obstruction and the need for
      subsequent urethral procedures. We present methodology for a prospective cohort
      study analyzing the outcomes of PR versus suprapubic cystostomy tube (SPT) after
      PFUI. Methods: A prospective cohort trial was designed to compare outcomes
      between PR (group 1) and SPT placement (group 2). Centers are assigned to a group
      upon entry into the study. All patients will undergo retrograde attempted
      catheter placement; if this fails a cystoscopy exam is done to confirm a complete
      urethral disruption and attempt at gentle retrograde catheter placement. If
      catheter placement fails, group 1 will undergo urethral realignment and group 2
      will undergo SPT. The primary outcome measure will be the rate of urethral
      obstruction preventing atraumatic passage of a flexible cystoscope. Secondary
      outcome measures include: subsequent urethral interventions, post-injury
      complications, urethroplasty complexity, erectile dysfunction (ED) and urinary
      incontinence rates. Results: Prior studies demonstrate PR is associated with a
      15% to 50% reduction in urethral obstruction. Ninety-six men (48 per treatment
      group) are required to detect a 15% treatment effect (80% power, 0.05
      significance level, 20% loss to follow up/death rate). Busy trauma centers treat
      complete PFUI approximately 1-6 times per year, thus our goal is to recruit 25
      trauma centers and enroll patients for 3 years with a goal of 100 or more total
      patients with complete urethral disruption. Conclusions: The proposed prospective
      multi-institutional cohort study should determine the utility of acute urethral
      realignment after PFUI.

PMID- 30211043
TI  - Racial distribution of urology workforce in United States in comparison to
      general population.
AB  - Background: To compare the current racial/ethnic characteristics of practicing
      urologists to the U.S. population by American Urological Association (AUA) census
      geographic region. Methods: We compared urologist demographics from the 2014 AUA
      census to U.S. census data. Underrepresented in medicine (URM) status was defined
      as African-American (AA) or Hispanic race/ethnicity. Percent differences by AUA
      section were calculated by subtracting weighted frequencies of race/ethnicity for
      urologists from the general population. A negative percent difference denotes
      underrepresentation of urologists relative to the general population; positive
      percent difference denotes overrepresentation. Results: URM urologists (n=728,
      6.5%) were younger and more often female than non-URM counterparts. Overall, AA
      and Hispanic urologists were underrepresented in most sections while Caucasian
      and Asian urologists were overrepresented. AA urologists were most
      underrepresented in the East South-Central section (-34.4%). Hispanic urologists
      (-38%) were most underrepresented in the Pacific section (-38%). Overall, the
      percentage of URM urologists, compared to non-URM urologists, were highest in the
      South Atlantic [37.9% (276/728) vs. 19.2% (1,984/10,319), P<0.01] and West South
      Central [15.9% (116/728) vs. 11.1% (1,143/10,319), P<0.01]. Conclusions: URM
      urologists tend to be younger with a higher proportion of female providers,
      indicating a shift in race and gender. URM urologists were most underrepresented
      in the East South-Central and Pacific sections.

PMID- 30211044
TI  - Use of angioembolization in urology: a review.
AB  - This review discusses current and developing indications for angioembolization
      (AE) techniques in urology cases, including trauma and non-trauma uses for
      kidney, prostate, and bladder conditions. AE methods, complications and technical
      and clinical outcomes are outlined for each indication for the purpose of aiding
      urologists in selecting ideal candidates for this procedure.

PMID- 30211045
TI  - Robotics and urologic reconstructive surgery.
AB  - Minimally invasive surgery has made a profound impact on how urologists approach
      the challenges in reconstruction of the urinary tract. The advent of laparoscopic
      approaches to reconstructive urology have demonstrated comparable outcomes to
      open surgery with improved morbidity. The recent adoption of robotic surgery has
      seen further advancements such as improved visibility and, freedom of movement,
      and an easier technical learning curve. With these advantages, more
      reconstructive urology procedures are being performed robotically. Herein, we
      review reconstructive urology procedures for which robotics have been applied.

PMID- 30211046
TI  - Long-term complications of continent catheterizable channels: a problem for
      transitional urologists.
AB  - A majority of the transitional urology patient population have neurogenic bladder
      and many of these patients have undergone creation of continent catheterizable
      channels (CCCs) to facilitate bladder emptying. Transitional urologists will be
      faced with revision of these channels due to a variety of possible complications.
      We performed a comprehensive literature review to the data regarding the
      incidence, timing, and predisposing factors that lead to complications of CCCs as
      well as surgical revision techniques and their outcomes. Long-term channel
      complications and related revisions are common (25-30%) and likely
      underestimated. While many predictors for revision have been posited, the only
      predictor that has been significant in robust multivariable analysis is channel
      type, with appendicovesicostomies having a lower chance of requiring revision
      compared to Monti channels. Channels created in adults have high likelihood of
      requiring revision, even within a relatively short follow-up period. We review
      techniques for management of channel complications and their outcomes. As
      patients with congenital urologic conditions requiring CCCs are gaining longer
      lifespans, transitional urologists will be faced with revision and/or replacement
      of these channels. While some of these patients may require supravesical
      diversion in the future, data show that revision is feasible with good outcomes.
      Longer-term follow-up data is needed to understand the life-span and best
      practices of new CCCs created among the transitional population.

PMID- 30211047
TI  - Anatomy and techniques in posterior urethroplasty.
AB  - Given its complex anatomy, injury to the posterior urethra may result in a number
      of reconstructive challenges. With the appropriate operative planning and
      experience, surgical repair can be very successful. This review discusses the
      applicable techniques for the perineal approach to posterior urethral stenosis,
      including bulbomembranous anastomosis for pelvic fracture urethral injury and
      repair of vesicourethral anastomotic stenosis (VUAS) following prostate surgery.
      The advanced techniques reviewed include an adaptation allowing a bulbar artery
      sparing approach to posterior urethroplasty and an intrasphincteric urethroplasty
      procedure which may allow continence preservation in patients with membranous
      urethral stenosis.

PMID- 30211049
TI  - Current management of pelvic fracture urethral injuries: to realign or not?
AB  - The acute management of pelvic fracture urethral injuries (PFUIs) remains a
      controversial topic. Currently, suprapubic tube (SPT) placement with delayed
      repair or primary realignment (PR) represents the strategies used to treat
      patients. While many will advocate the use of one technique over the other, the
      2014 American Urological Association (AUA) Guidelines give providers the option
      for the management PFUI. Current literature evaluates these two interventions,
      focusing on the incidence of re-stricture formation, erectile dysfunction, and
      urinary incontinence. Here we perform a comprehensive review of the current
      management for PFUI, as well as, discuss the limitations of the studies and need
      for more prospective studies on this debated topic.

PMID- 30211048
TI  - Posterior urethral stenosis after prostate cancer treatment: contemporary options
      for definitive management.
AB  - Posterior urethral stenosis (PUS) is an uncommon but challenging problem
      following prostate cancer therapy. A review of the recent literature on the
      prevalence of PUS and treatment modalities used in the last decade was performed.
      A summative narrative of current accepted techniques in management of PUS is
      presented, and supplement with our own experience and algorithms.

PMID- 30211051
TI  - Evaluation and management of adult acquired buried penis.
AB  - Adult acquired buried penis represents the clinical manifestation of a wide
      spectrum of pathology due to a variety of etiologies. It can be related to
      obesity, a laxity in connective tissue, lichen sclerosis (LS), complications from
      penile/scrotal enlargement surgery, scrotal lymphedema, or hidradenitis
      suppurativa (HS). Buried penis can be associated with poor cosmesis and hygiene,
      voiding dysfunction, and sexual dysfunction. Evaluation and management of buried
      penis largely depends on etiology and degree of affected tissue. It is an
      increasingly common problem seen by reconstructive urologists and here we present
      several frequently seen scenarios of buried penis and management options.

PMID- 30211050
TI  - Contemporary surgical and non-surgical management of Peyronie's disease.
AB  - Numerous treatments have been proposed for Peyronie's disease (PD). As the
      evidence base has expanded, the field of operative and non-operative options for
      patients has narrowed. Collagenase clostridium hystolyticum (CCH) injection now
      comprises the medical option, and surgical possibilities entail penile plication,
      plaque incision/excision and grafting, and prosthesis implantation. Still,
      questions abound regarding the optimal approach and indication for each of these
      treatments. We conducted a review of literature exploring the contemporary
      management of PD with a particular focus on work since the last American Urologic
      Association's (AUA) guidelines update for PD. Recent results and discussion
      indicate trends toward minimal invasiveness, toward a more holistic approach to
      the PD patient, and away from algorithmic management, galvanized, in part, by
      data challenging long-held beliefs.

PMID- 30211053
TI  - Penile transplantation: the US experience and institutional program set-up.
AB  - Penile transplantation using vascularized composite allografts is an emerging
      technique to treat genital loss. In the United States, this procedure has been
      performed successfully at Massachusetts General Hospital in a patient who had
      previously undergone treatment for penile cancer. The Johns Hopkins Medical
      Institutions has developed a research protocol to perform penile transplantation
      in patients with genital loss secondary to trauma. The process of selecting the
      appropriate candidate for genitourinary (GU) vascularized composite allograft
      surgery is rigorous including extensive physical examination, laboratory testing,
      imaging and psychological evaluations. After transplantation, limiting the
      potential complications associated with immunosuppression is critical given that
      the procedure is intended to improve quality of life and is not life-saving.
      Ultimately, penile transplant is a surgical intervention which may have numerous
      applications. Optimization of the pre-operative screening process, surgical
      technique, and immunosuppressive protocol is required to establish this method as
      the standard treatment for patients with genital loss and limited reconstructive
      options.

PMID- 30211052
TI  - Novel surgical techniques in female to male gender confirming surgery.
AB  - The current management of female to male (FTM) gender confirmation surgery is
      based on the advances in neo phalloplasty, perioperative care and the knowledge
      of the female genital anatomy, as well as the changes that occur to this anatomy
      with preoperative hormonal changes in transgender population. Reconstruction of
      the neophallus is one of the most difficult elements in surgical treatment of
      female transsexuals. While there is a variety of available surgical techniques,
      their results are not equally acceptable to all patients. The preference for a
      particular surgical technique mostly depends on the patient's desires and
      expectations. Nevertheless, the surgeon's duty is to fully inform the patient
      about all the advantages and disadvantages, as well as all complications that
      might occur after surgical procedure-and even to talk them out of a desired
      surgical technique if there are contraindications. Metoidioplasty is a
      technically demanding surgical procedure used in FTM transsexuals who desire a
      gender reassignment surgery (GRS) without undergoing a complex, multi-staged
      surgical creation of an adult-sized phallus. Metoidioplasty is viable in cases
      where the clitoris seems large enough after androgen hormonal treatment. Since
      the clitoris plays the main role in female sexual satisfaction, its impact on the
      outcome of FTM transgender surgery is predictable. Various free flaps have been
      reported for total phalloplasty, such as radial forearm flap, latissimus dorsi
      flap, anterolateral tight flap, different abdominal wall flaps, free deltoid
      flap, scapular free flap, sensate osteocutaneous free fibula flap, tensor fasciae
      latae, deep epigastric artery perforator flap and dorsalis pedis flap. The fact
      that there are so many techniques for penile reconstruction in cases of penis
      absence, proves that none of the above mentioned techniques succeeded in
      achieving the ideal goals of penis reconstruction. We will emphasize the most
      commonly used surgical techniques in genital confirmation in FTM transsexuals
      with reference to respective eligibility criteria for each procedure.

PMID- 30211054
TI  - Military genitourinary injuries: past, present, and future.
AB  - Genitourinary (GU) injuries among military service members are as old as war
      itself. The frequency and clinical picture of GU injuries sustained in conflicts
      over the ages have evolved along with the constantly changing nature of combat.
      In this review, we discuss changing trends in the diagnosis and management of GU
      injuries over the past century and introduce areas of innovation which could
      impact the care of casualties who sustain GU trauma in the future.

PMID- 30211055
TI  - Stem cell in urology-are we at the cusp of a new era?
AB  - Stem cell therapy can potentially disrupt conventional medicine as we practice it
      today. Stem cells can self-renew and differentiate and by this, repair and in
      certain conditions regenerate damaged tissue. In the past two decades, there has
      been significant research into its value in several chronic urological conditions
      for which conventional therapy is unsatisfactory. Stem cell therapy has been
      tried on animal models of bladder dysfunction, stress urinary incontinence (SUI),
      erectile dysfunction and urethral injury and certain preclinical studies have had
      very encouraging results. Yet despite this explosion of knowledge about the
      nature and value of stem cells, translation of research into the clinical domain
      has been slow. In addition, lack of regulation of stem cell therapy has resulted
      in indiscriminate, unscientific administration of stem cell therapy to patients.
      This review looks into the advances in the use of stem cells in urological
      practice, the recent regulatory guidelines that have been introduced and what the
      future holds for this exciting branch.

PMID- 30211056
TI  - International volunteerism and urethral stricture disease: a review.
AB  - Global health is an ever-expanding area of interest for many healthcare workers
      around the world. In recent years, it has become apparent that much of the global
      disease burden is surgical. Urologic disease is no exception-many international
      organizations send volunteers around the world to support Urologic services in
      countries that lack capacity and resources. Urethral stricture represents a
      unique opportunity for specialized surgical management that vastly improves long
      term morbidity. Here we review the prevalence, etiology, and management of
      urethral stricture from a global perspective while highlighting impact of
      international urologic volunteer efforts.

PMID- 30211057
TI  - Training in reconstructive urology: the past, present and future.

PMID- 30211058
TI  - Effect of body mass index on recurrence following urethroplasty.
AB  - Background: Limited investigation exists to understand whether obesity affects
      outcomes of urethral reconstruction. We sought to assess whether body mass index
      (BMI) is an independent predictor for stricture recurrence following
      urethroplasty. Methods: We performed a retrospective review of patients
      undergoing urethroplasty between 2007-2014, identifying 137 patients for study
      inclusion. Data collected included BMI and patient demographic and surgical
      characteristics, including age, stricture length and location, etiology, and
      urethroplasty technique. Stricture-free survival analysis was performed using
      Kaplan-Meier method. Logistic regression was performed to assess predictors for
      stricture recurrence using both univariate and multivariate models. Results: Mean
      patient age and follow-up was 46.7 (+/-16.4) years and 91.8 (+/-30.5) months,
      respectively. A recurrence rate of 17% was identified, with a mean time to
      recurrence of 29 months. There was no difference when comparing the mean BMI in
      patients with and without recurrence (28.9 vs. 30.4 kg/m2, respectively) (P=0.4).
      A higher rate of stricture recurrence was seen when comparing the cohort with a
      BMI <25 kg/m2 versus remaining cohorts (BMI: 25-30 kg/m2; BMI >30 kg/m2).
      However, in univariate and multivariate analysis, BMI failed to demonstrate
      statistical significance as a predictor for urethroplasty outcome. On
      multivariate analysis, fasciocutaneous repair type was predictive of stricture
      recurrence. No additional potential predictors assessed were found to be
      significant. Conclusions: In the present study, BMI did not independently predict
      for stricture recurrence following urethroplasty.

PMID- 30211059
TI  - The use of assisted reproductive technology before male factor infertility
      evaluation.
AB  - Background: Some centers offer assisted reproductive technologies (ARTs) [intra
      uterine insemination (IUI) and in-vitro fertilization (IVF)], to treat certain
      couples with male factor infertility without having the men assessed by male
      infertility specialists. We sought to compare characteristics of couples having
      or not having prior ART use. Methods: We used our prospectively collected
      database to identify men undergoing an initial evaluation for male infertility
      between 1995-2017. We obtained data on patient demographics, use of IUI and IVF,
      and semen analysis parameters. We used multivariable logistic regression to
      identify characteristics associated with prior use of ART. Results: One thousand
      and five hundred forty-five out of 8,962 (17.2%) men reported use of ARTs prior
      to evaluation. Of these, 258 tried both IUI and IVF. More than one attempt was
      reported in 470 (37.2%) and 154 (28.2%) of men with prior IUI and IVF,
      respectively. Younger male age [adjusted odds ratio (aOR) 0.97/year; 95%
      confidence interval (CI), 0.95 to 0.99], older female partner age (aOR 1.07/year;
      95% CI, 1.04 to 1.10), and year of visit (aOR 1.05/year; 95% CI, 1.01 to 1.09)
      were significantly associated with prior IUI. Older female partner age (aOR
      1.07/year; 95% CI, 1.02 to 1.12) was significantly associated with prior IVF, but
      not male age or year of visit. Semen analysis parameters were not associated with
      prior ART. Conclusions: The prior use of ART is common among men presenting for
      an initial evaluation at a male infertility specialty clinic. Older female
      partner age was associated with use of reproductive technologies prior to
      evaluation, however, semen analysis parameters were not.

PMID- 30211062
TI  - Is sexual education an important skill to teach in medical schools?

PMID- 30211063
TI  - What can the National Cancer Database tell us about disparities in advanced
      bladder cancer outcomes?

PMID- 30211061
TI  - Urethral diverticulum carcinoma in females-a case series and review of the
      English and Japanese literature.
AB  - The aims of our study were to describe our case series of three urethral
      diverticulum carcinomas (UDC) in women and to review the literature on UDC in
      females to determine patient characteristics, presenting symptoms and outcomes
      along with optimal investigations and treatment modalities. A literature search
      was performed utilizing Medline, EMBASE and the Cochrane library for all papers
      including case reports on UDC in women published to date. The results along with
      those of our three cases are detailed. A total of 126 cases of UDC in women have
      been reported; 75% adenocarcinoma (Adenoca), 15% transitional cell carcinoma
      (TCC) and 10% squamous cell carcinoma (SCC). Median age at presentation was 53
      years (range, 14-81 years). The commonest presenting symptoms were bleeding and
      retention. Cystoscopy, MRI and trans-urethral biopsy were the commonest methods
      of diagnosis. Treatment was radiotherapy +/- chemotherapy alone in 21%, local
      excision +/- radiotherapy in 44%, urethrectomy in 3% and anterior exenteration +/
      radiotherapy in 32%. At last follow-up 63% were alive and well, 10% were alive
      with recurrent cancer and 25% had died from their disease. UDC is rare in women.
      It is predominantly adenocarcinoma. There is no established treatment and
      survival is at best moderate. An international registry and consensus on
      management is needed if this is to be improved.

PMID- 30211060
TI  - Contemporary management of ejaculatory dysfunction.
AB  - Although erectile dysfunction is the most common disorder of male sexual health,
      ejaculatory dysfunction is the most common form of sexual dysfunction experienced
      by men. Ejaculatory dysfunction covers a broad range of disorders that we have
      divided into four main categories: premature ejaculation, delayed ejaculation
      (DE)/anorgasmia, unsatisfactory sensation of ejaculation (including painful
      ejaculation and ejaculatory anhedonia), and absent ejaculate (including
      retrograde ejaculation and aspermia). We also cover several special scenarios
      including hematospermia, spinal cord injury and fertility with anejaculation. In
      this paper, we will review the anatomy and pathophysiology of normal ejaculation
      to establish the baseline knowledge of how this pathway can go awry. We will then
      briefly review the critical diagnostic criteria, pertinent steps in evaluation,
      risk factors, and causes (if known) for each of the ejaculatory disorders.
      Finally, the bulk of the paper will discuss current management strategies of each
      disorder.

PMID- 30211064
TI  - The value of molecular markers in classification and prediction of progression in
      non-muscle-invasive bladder cancer.

PMID- 30211065
TI  - Bladder utility symptom scale: a new patient reported outcome measure for health
      related quality of life in bladder cancer.

PMID- 30211066
TI  - Evaluating the role of neoadjuvant chemotherapy in bladder cancer patients with
      occult lymph node metastases.

PMID- 30211067
TI  - Open radical cystectomy: lessons from the British Association of Urological
      Surgeons (BAUS) registry.

PMID- 30211068
TI  - Prediction of progression to muscle-invasive disease in patients with high-risk
      bladder cancer.

PMID- 30211069
TI  - The role of antibiotic prophylaxis after radical cystectomy in preventing urinary
      tract infections and readmission for sepsis.

PMID- 30211070
TI  - Exploring trends in advanced bladder cancer using the NCDB: turning data into
      information and information into insight.

PMID- 30211071
TI  - Refining the use of neoadjuvant chemotherapy in locally advanced bladder cancer:
      from conviction to optimization.

PMID- 30211072
TI  - Stage T1 bladder cancer: historic background and latest tracks for its
      demystification.

PMID- 30211073
TI  - Erratum to expanded criteria for active surveillance in prostate cancer: a review
      of the current data.
AB  - [This corrects the article DOI: 10.21037/tau.2017.08.23.].

PMID- 30211074
TI  - Enzyme replacement therapies: what is the best option?
AB  - Despite many beneficial outcomes of the conventional enzyme replacement therapy
      (ERT), several limitations such as the high-cost of the treatment and various
      inadvertent side effects including the occurrence of an immunological response
      against the infused enzyme and development of resistance to enzymes persist.
      These issues may limit the desired therapeutic outcomes of a majority of the
      lysosomal storage diseases (LSDs). Furthermore, the biodistribution of the
      recombinant enzymes into the target cells within the central nervous system
      (CNS), bone, cartilage, cornea, and heart still remain unresolved. All these
      shortcomings necessitate the development of more effective diagnosis and
      treatment modalities against LSDs. Taken all, maximizing the therapeutic response
      with minimal undesired side effects might be attainable by the development of
      targeted enzyme delivery systems (EDSs) as a promising alternative to the LSDs
      treatments, including different types of mucopolysaccharidoses ( MPSs ) as well
      as Fabry, Krabbe, Gaucher and Pompe diseases.

PMID- 30211075
TI  - Risk association, linkage disequilibrium and haplotype analyses of FASN
      rs4246445, rs2229425, rs2228305 and rs2229422 polymorphisms in overweight and
      obesity.
AB  - Introduction: Obesity is commonly linked up with several life-threatening
      diseases. This study aims to investigate the association of fatty acid synthase
      (FASN) rs4246445, rs2229425, rs2228305, and rs2229422 single nucleotide
      polymorphisms (SNPs) with the risk of overweight and obesity in the Malaysian
      population. Methods: Blood samples were collected from 1030 individuals who were
      grouped into normal, overweight, and obese categories. Blood biochemistry test
      and lipid profiling were performed and genomic DNA was extracted. Genotyping was
      performed using hydrolysis probes and odd ratio with 95% CI was calculated for
      risk association analysis. Linkage disequilibrium and haplotypes analyses were
      carried out using SHEsis software. Results: We found that the hemoglobin and
      white blood cell counts were significantly high in the obese subjects. There is a
      lack of evidence to link the FASN SNPs with the risk of overweight and obesity in
      the population. All 4 SNPs were seemed to be in linkage equilibrium. Five common
      haplotypes were identified in this study but none of them was significantly
      associated with overweight and obesity in the population. Conclusion: Our
      findings suggest a lack of evidence to associate the FASN rs4246445, rs2229425,
      rs2228305, and rs2229422 SNPs with the risk of overweight and obesity in the
      Malaysian population. All 4 SNPs were independent of each other and not all
      identified haplotypes were significantly associated with overweight and obesity
      in this study.

PMID- 30211076
TI  - Expression, purification and DNA-binding properties of zinc finger domains of DOF
      proteins from Arabidopsis thaliana.
AB  - Introduction: DOF proteins are a family of plant-specific transcription factors
      with a conserved zinc finger (ZF) DNA-binding domain. Although several studies
      have demonstrated their specific DNA binding, quantitative affinity data is not
      available for the binding of DOF domains to their binding sites. Methods: ZF
      domains of DOF2.1, DOF3.4, and DOF5.8 from Arabidopsis thaliana were expressed
      and purified. Their DNA binding affinities were assessed using gel retardation
      assays and microscale thermophoresis with two different oligonucleotide probes
      containing one and two copies of recognition sequence AAAG. Results: DOF zinc
      finger domains (DOF-ZFs) were shown to form independently folded structures.
      Assessments using microscale thermophoresis demonstrated that DOF-ZFs interact
      more tightly (~ 100 fold) with double-motif probe than the single-motif probe.
      The overall Kd values for the DOF3.4-ZF and DOF5.8-ZF to the double-motif probe
      were ~2.3+/-1 and 2.5+/-1 uM, respectively. Conclusion: Studied DOF-ZF domains
      formed stable complexes with the double-motif probe. Although DOF3.4-ZF and
      DOF5.8-ZF do not dimerize with an appreciable affinity in the absence of DNA
      (judging from size-exclusion and multiangle laser light scattering data), it is
      possible that these ZFs form protein-protein contacts when bound to this
      oligonucleotide, consistent with previous reports that DOF proteins can homo- and
      hetero-dimerize.

PMID- 30211077
TI  - Altered levels of immune-regulatory microRNAs in plasma samples of patients with
      lupus nephritis.
AB  - Introduction: Lupus nephritis (LN) is a major cause of mortality and morbidity in
      the patients with lupus, a chronic autoimmune disease. The role of genetic and
      epigenetic factors is emphasized in the pathogenesis of LN. The aim of the
      present study was to evaluate the levels of immune-regulatory microRNAs (e.g.,
      miR-31, miR-125a, miR-142-3p, miR-146a, and miR-155) in plasma samples of
      patients with LN. Methods: In this study, 26 patients with LN and 26 healthy
      individuals were included. The plasma levels of the microRNAs were evaluated by a
      quantitative real-time PCR. Moreover, the correlation of circulating plasma
      microRNAs with disease activity and pathological findings along with their
      ability to distinguish patients with LN were assessed. Results: Plasma levels of
      miR-125a (P = 0.048), miR-146a (P = 0.005), and miR-155 (P< 0.001) were
      significantly higher in comparison between the cases and controls. The plasma
      level of miR-146a significantly correlated with the level of anti-double strand
      DNA antibody and proteinuria. Moreover, there was a significant correlation
      between miR-142-3p levels and disease chronicity and activity index (P <0.05).
      The multivariate ROC curve analysis indicated the plasma circulating miR-125a,
      miR-142-3p, miR-146, and miR-155 together could discriminate most of the patients
      with LN from controls with area an under curve (AUC) of 0.89 [95% CI, 0.80-0.98,
      P<0.001], 88% sensitivity, and 78% specificity. Conclusion: Based on the findings
      of the present study, the studied microRNAs may be involved in the pathogenesis
      and development of LN and have the potential to be used as diagnostic and
      therapeutic markers in LN.

PMID- 30211079
TI  - Numerical investigation of the blood flow through the middle cerebral artery.
AB  - Introduction: The middle cerebral artery (MCA) is one of the three major paired
      arteries that supply the blood to the cerebrum. In the present study, the three
      dimensional (3D) blood flow in the left MCA was numerically simulated by using
      the medical imaging. Methods: The arterial geometry was obtained by applying the
      CT angiography of the MCA of a 75-year-old man. The blood flow was assumed to be
      laminar and unsteady. Numerical simulations were done by commercial software
      package COMSOL Multiphysics 5.2. In this software, the Galerkin's finite element
      method was applied to solve the governing equations. Results: It was found that
      the results obtained for the Newtonian and non-Newtonian models of blood do not
      differ from each other significantly. Thus, the Newtonian model for blood flow in
      the MCA is acceptable. Also, the most susceptible region of the MCA for
      Atherosclerosis was detected. Conclusion: It can be concluded that the
      application of the Newtonian model for the blood flowing in the MCA is
      acceptable. Also, atherosclerosis has the potential to occur at the middle of a
      branch of the MCA which has the highest geometrical curvature.

PMID- 30211078
TI  - Gallic acid and curcumin induce cytotoxicity and apoptosis in human breast cancer
      cell MDA-MB-231.
AB  - Introduction: Gallic acid (GA) and curcumin (Cur) are natural phenolic compounds
      that their anti-tumor effects on many types of cancers have been proved. In the
      current study, the effect of the combination of these agents on MDA-MB-231 breast
      cancer cells was investigated. Methods: Inhibition of cell proliferation (MTT
      assay), light microscopy, fluorescence microscopy, cell cycle analysis, nitrite
      detection, ROS levels, measurement of the mitochondrial membrane potential, GSH
      level, Annexin V assay, RT-PCR and Western blotting methods were applied.
      Results: The results revealed the combination of GA and Cur strongly decreased
      MDA-MB-231 cell growth. Moreover, this combination increased ROS level and
      cytotoxic activity along with the glutathione depletion in MDA-MB-231 cells. Flow
      cytometry analysis showed the combination of GA and Cur increased sub-G1 cell
      population. Furthermore, fluorescent staining and Annexin V/PI assay showed that
      apoptotic cells were significantly increased in the presence of GA and Cur. At
      last, protein expression evaluation showed that the combination of GA and Cur
      significantly decreased Bcl-2 level while increased Bax, cleaved-caspase3 and
      PARP levels in MDA-MB-231 cells. Conclusion: These results suggest that GA in
      combination with Cur could be a possible candidate for chemoprevention agent of
      triple negative breast cancer.

PMID- 30211080
TI  - In silico identification of albendazole as a quorum sensing inhibitor and its in
      vitro verification using CviR and LasB receptors based assay systems.
AB  - Introduction: Quorum sensing inhibition (QSI) is one of the vital tools to
      overcome emerging virulence of pathogenic bacteria which aims at curbing
      bacterial resistance. Targeting QS (quorum sensing) as chemotherapy is less
      likely to generate resistance among pathogens as it targets only the adaptation
      and not the survival mechanism of the pathogen. Several QS inhibitors were
      developed in the recent past but none of them managed to have clinical
      application due to known toxic effects for human consumption. A rapid development
      of QS inhibitor drugs could be achieved by verification of the QSI activity of
      drugs which are already in clinical use with known pharmacology. Recently, a
      known FDA approved clinical drug niclosamide belonging to an anthelmintic class
      is found to exhibit QSI activity. Methods: We have focused our study on
      Albendazole, another FDA approved clinical drug belonging to the same class for
      its potential to act as QSI. The structure-based molecular docking is used for
      finding putative interactions made by this drug with the CviR and LasB receptor
      protein of Chromobacterium violaceum and Pseudomonas aeruginosa , respectively.
      Further, the in vitro activity of this drug has been evaluated by employing CviR
      and LasB receptor-based bioassay. The efficacy of this drug alone and in
      combination with antibiotic Tobramycin to inhibit P. aeruginosa based biofilms
      was also analyzed by developing the biofilms on chambered glass slides and
      performing anti-biofilm assay. Results: Further, this drug found to inhibit
      purple pigment violacein production in C. violaceum , which is under the control
      of C6-AHL-CviR mediated QS in this human pathogen. The in vivo bioassays results
      suggested that albendazole has great potential to act as a QS inhibitor as found
      inhibiting violacein production in C. violaceum and biofilm formation in P.
      aeruginosa , respectively. Conclusion: It is that structure-based molecular
      docking guided bioassay evaluation is an efficient tool for finding the new
      therapeutic use of old drugs which could have more chances to come easily in
      clinical application for their newly identified therapeutic uses.

PMID- 30211083
TI  - Effectiveness of Type I Tympanoplasty in Wet and Dry Ear in Safe Chronic
      Suppurative Otitis Media.
AB  - The aims and objectives of the study were to compare the rate of graft uptake
      after type 1 tympanoplasty in wet and dry ears and also to compare the
      postoperative hearing improvement in wet and dry ears. It was a Non Randomized
      Experimental Study. This study was done in ENT OPD at Tertiary Health Care
      Institute of Central India. It was conducted from November 2012 to October 2014
      on 86 patients having Safe Chronic Suppurative Otitis Media. The patients were
      divided into two groups as Dry ear group and Wet ear group. Dry ear group
      included patients whose ear was dry for at least 6 weeks prior to the surgery.
      Wet ear group included patients who had minimal mucoid discharge in the middle
      ear which on culture and sensitivity showed no microorganisms. Type 1
      Tympanoplasty was done in all patients. Results were analyzed statistically.
      Complete graft uptake was seen in 86.95% cases of Dry ear group and 80% of Wet
      ear group and the difference was statistically insignificant. Hearing improvement
      was achieved in 80% cases in dry group and 67.5% cases in wet group. The
      difference in hearing improvement in both groups was also statistically
      insignificant. So conclusion was drawn that, presence of minimal mucoid ear
      discharge at the time of surgery does not affect the success rate of Type 1
      Tympanoplasty.

PMID- 30211081
TI  - A cancer vaccine with dendritic cells differentiated with GM-CSF and IFNalpha and
      pulsed with a squaric acid treated cell lysate improves T cell priming and tumor
      growth control in a mouse model.
AB  - Introduction: Ovarian cancer is one of the most lethal gynecologic cancers.
      Relapses after remission are common, hence novel strategies are urgently needed.
      Our group has previously developed a vaccination approach based on dendritic
      cells pulsed with HOCl-oxidized tumor lysates. Here we investigate the
      improvement of this vaccine strategy using squaric acid treatment of cancer cells
      during tumor lysate preparation and by differentiating dendritic cells in the
      presence of GM-CSF and IFNalpha. Methods: Induction of cell death by squaric acid
      treatment was assessed with propidium iodide (PI) and Annexin V in ID8 tumor
      cells. High mobility group box 1 (HMGB1) immunogenic status was analyzed using a
      western blot-based method, as previously described. For immunological tests, ID8
      cells expressing ovalbumin (ova-ID8) were treated with squaric acid before cell
      lysis. DCs prepared with the canonical GM-CSF and IL-4 differentiation cocktail
      or IFNalpha and GM-CSF were pulsed with tumor cell lysates and further matured in
      the presence of IFNgamma and LPS (4-DCs and alpha-DCs respectively). DCs were
      then used in co-culture assays with ova-specific T cells and IFNgamma and IL-4
      secretion measured by ELISA. DC phenotypes were characterized by FACS. Finally,
      DCs were tested in an ovarian cancer mouse model measuring body weight and animal
      survival. Results: Squaric acid treatment of mouse ovarian cancer cells induced
      tumor cell death as well as preserve HMGB1, a crucial Damage-associated molecular
      pattern (DAMP) signal, in its active reduced form. Squaric acid treatment of ID8
      ova cells increased IFNgamma and decreased IL-4 production from ova-specific T
      cells in co-culture experiments, promoting a more immunogenic cytokine secretion
      pattern. DCs differentiated in the presence of IFNalpha induced a considerable
      decrease in IL-4 production compared to canonical 4-DCs, without affecting
      IFNgamma release. DC phenotyping demonstrated a more mature and immunogenic
      phenotype for IFNalpha-differentiated DCs. Vaccination in tumor-bearing mice
      showed that IFNalpha-differentiated DCs pulsed with squaric acid-treated lysates
      were the most potent at delaying tumor growth, improving animal survival.
      Conclusion: We identified squaric acid as a novel immunogenic treatment of tumor
      cells for cancer vaccines particularly efficient in prolonging animal survival
      when used in combination with IFNalpha-differentiated DCs. These promising
      results support future efforts for the clinical translation of this approach.

PMID- 30211084
TI  - Knowledge, Attitude of Sikkim Primary School Teachers About Paediatric Hearing
      Loss.
AB  - Our purpose of the study was to assess the knowledge and any gaps of early
      educators regarding hearing impairment, and to attempt to delineate the attitudes
      and perceptions of the educators regarding the outcomes of their students with
      hearing disabilities and their views on inclusive teaching, using a questionnaire
      based study. Only 71 respondents completed the questionnaire. The present
      questionnaire based study was conducted on 100 primary school teachers,
      undertaken on randomly selected schools from Gangtok, East Sikkim. Their
      knowledge and attitudes regarding hearing impairment in children in the areas of
      cause, diagnosis, investigations, treatment, prevention, special care and
      inclusion into mainstream schools were assessed. Our study showed that the
      knowledge of causes, investigation and treatment of hearing impairement [HI]
      among respondents/teachers was poor. The data was shown statistically significant
      with P < 0.001. However, responses testing behavior and attitudes towards HI was
      encouraging. 52.9% respondents disagreed that HI was a social handicap and 88.2%
      felt that teachers need special training before a HI child is admitted to the
      school. The results were statistically significant with P < 0.001. The biggest
      obstacle found for inclusive education of HI children was a lack of proper
      training to teachers (40.8%) and attitude of other students (29.5%).

PMID- 30211082
TI  - Breast cancer vaccination comes to age: impacts of bioinformatics.
AB  - Introduction: Breast cancer, as one of the major causes of cancer death among
      women, is the central focus of this study. The recent advances in the development
      and application of computational tools and bioinformatics in the field of
      immunotherapy of malignancies such as breast cancer have emerged the new dominion
      of immunoinformatics, and therefore, next generation of immunomedicines .
      Methods: Having reviewed the most recent works on the applications of
      computational tools, we provide comprehensive insights into the breast cancer
      incidence and its leading causes as well as immunotherapy approaches and the
      future trends. Furthermore, we discuss the impacts of bioinformatics on different
      stages of vaccine design for the breast cancer, which can be used to produce much
      more efficient vaccines through a rationalized time- and cost-effective in silico
      approaches prior to conducting costly experiments. Results: The tools can be
      significantly used for designing the immune system-modulating drugs and vaccines
      based on in silico approaches prior to in vitro and in vivo experimental
      evaluations. Application of immunoinformatics in the cancer immunotherapy has
      shown its success in the pre-clinical models. This success returns back to the
      impacts of several powerful computational approaches developed during the last
      decade. Conclusion: Despite the invention of a number of vaccines for the cancer
      immunotherapy, more computational and clinical trials are required to design much
      more efficient vaccines against various malignancies, including breast cancer.

PMID- 30211085
TI  - Incidence and Treatment Outcomes of Post Traumatic BPPV in Traumatic Brain Injury
      Patients.
AB  - The aim of this study is to assess the incidence of post traumatic BPPV and
      evaluate its treatment outcomes in mild and moderate traumatic head injury
      patients. The study population consisted of 128 patients (89 male:39 female) who
      were admitted with head and neck injury (Motor Vehicle Accident, Blow to the
      head, Fall from Height, Whiplash injury) as inpatients in Department of
      Neurosurgery in Tertiary care hospital in Kerala during a 2 month period from 1st
      April 2014 to 31st May 2014. The age range was 10-70 years and mean 39.8 with
      standard deviation 15.5. All cases were evaluated and serially followed up to a
      period of 6 months in Department of Otorhinolaryngology. In our study, the number
      of patients with mild injuries (Glasgow coma scale 13-15) were 108 and moderate
      injury (Glasgow coma scale 9-12) were 20. We found out that post traumatic BPPV
      was found to be 17% of the traumatic brain injury patients. All patients were
      treated with particle re-positioning maneuvers and were followed up for a period
      of 6 months. Recurrence were reported in 9 (40.9%) patients. In these patients re
      positioning maneuvers were repeated.

PMID- 30211086
TI  - Smart Phone Based Audiometry in City Traffic Police.
AB  - Noise induced hearing loss (NIHL) is defined as "reduction in auditory acuity
      associated with noise exposure". Traffic police is a bundle of people who are the
      usual sufferer of this type of increased hearing threshold. In developing
      countries like India, many of them are unable to access audiology services,
      because of shortage of trained professionals and limited sources. Smartphone
      based audiometry is easy and can detect hearing loss as early as possible. To
      study hearing threshold in traffic police. Total 88 persons were included in the
      study. An occupational history was taken regarding duration of posting followed
      by smart phone based audiometry (Hearing Test TM software) test. Out of total 88
      persons, 80 were having increased hearing thresholds which were suggestive of
      noise induced hearing loss. Out of total 88 persons 8 were in normal group, 24
      were in mild hearing loss group, 42 were in moderate hearing loss group and 14
      were in severe hearing loss group. Total number of person with notch at 4000/6000
      Hz was 28, suggestive of particular pattern of noise induced hearing loss. During
      the last decade, mobile phones have evolved like anything. Furthermore, the
      utilization of health-related applications has gained increased focus. Health
      related applications are useful, less time consuming and with increased
      efficiency by early diagnoses. There are many of smart-phone hearing applications
      that are already in use. They use similar principle as audiometer. This kind of
      application will narrow down the supply and demand ratio of audiology service in
      developing countries.

PMID- 30211087
TI  - Transcutaneous Columellar Strut for Correcting Caudal Nasal Septal Deviation.
AB  - Correction of caudal septal deviation is a challenging issue because of its
      significant role in tip support mechanisms. Some interventions especially
      aggressive resection of caudal septum to correct deviation, may compromise
      external nasal valve, tip ptosis and persistence of nasal obstruction. Many
      surgical techniques have been suggested to correct this type of nasal septal
      deviation. This study presents a technique to correct caudal septal deviation
      without weakening of tip support mechanisms. To evaluate the efficacy of
      insertion of a transcutaneous columellar strut during correction of caudal septal
      deviation. The study was performed in patients complaining from nasal obstruction
      with caudal septal deviation. After intranasal incision and elevation of
      mucoperichondrial flap, Caudal septum released from anterior nasal spine (ANS)
      and a band of cartilage removed from inferior and caudal part of septum and
      septum again fixed to ANS. Through a vertical transcutaneous incision, a
      cartilaginous strut is placed in columella, between medial crurae. Preoperative
      and postoperative NOSE score determined and photographs were taken. In 14
      patients we performed this technique, the postoperative NOSE score showed
      significant improvement, (p = 0.001). Nasal breathing improved in all patients
      without any complication or tip ptosis or worsening of nasal appearance. This
      septoplasty technique along with placement of transcolumellar strut, is an easy,
      efficient and complication free method for simultaneously correction of caudal
      deviation of nasal septum, reinforcing external nasal valve and prevents tip
      ptosis.

PMID- 30211088
TI  - A Comparative Study of Various Office Procedures for the Management of Small to
      Medium Size Tympanic Membrane Perforations.
AB  - A hospital based prospective study to compare and evaluate the efficacy and
      convenience of various office procedures like chemical cauterization, fat plug
      myringoplasty and butterfly cartilage tympanoplasty. This interventional,
      prospective, longitudinal study carried out on 300 patients in the ENT department
      of a tertiary care medical college hospital in central India between January 2009
      and January 2015. The success rate was found to be 94.54, 91.12 and 97% in
      chemical cauterization, fat plug and butterfly cartilage tympanoplasty
      respectively (p value 0.246). In all the groups there were significant
      improvement in terms of hearing in decibels and AB gap postoperatively. No
      statistically significant association was found in between the failure rates in
      all the groups. From this study we conclude that all the procedures were simple,
      rapid, reliable, cost effective, takes less time and minimum hospital stay (day
      care) than conventional tympanoplasty. We strongly recommend these procedures in
      place of tympanoplasty in small to medium size central tympanic membrane
      perforations according to condition and convenience of the patients.

PMID- 30211089
TI  - The Association Between Cochlear and Retrocochlear Disorders with Tinnitus with
      Normal Hearing Thresholds.
AB  - Tinnitus is the perception of hearing the sound without any sound stimulus. It is
      a symptom of abnormality in a form of conductive disorder when it comes from the
      outer ear canal and middle ear. A tinnitus complaint has a normal hearing
      threshold but it has been not fully recognized its causes. Thus, an objective
      evaluation is needed to locate the abnormality by using OAE and BERA test. To
      analyze the association of TEOAE, DPOAE, and BERA to locate cochlear and
      retrocochlear disorders in tinnitus patients with normal hearing threshold. The
      study was conducted from August to November 2010 until the number of samples was
      fulfilled in Outpatient Clinic and Audiology Unit in Department of Otolaryngology
      Head and Neck Surgery, Dr. Soetomo General Hospital Surabaya. The inclusion
      criteria in this study included: patients aged 20-50 years old, hearing threshold
      of <= 25 dB, type A tympanogram. The comparison and the association test of
      TEOAE, DPOAE and BERA in tinnitus group were: TEOAE-BERA analysis result using Mc
      Nemar obtained p = 0.006, Kappa p = 0.047, likelihood ratio p = 0.066, and the
      result of DPOAE-BERA analysis using Mc Nemar obtained p = 0.008, Kappa p = 0.439,
      likelihood ratio p = 0.336. There was a difference in the results of DPOAE
      examination between tinnitus patients with normal hearing threshold and the
      control group. There was no difference in TEOAE and BERA test results between
      tinnitus patients with normal hearing threshold and the control group. This
      indicates an abnormality in the cochlear.

PMID- 30211090
TI  - Reflux Finding Score (RFS) a Quantitative Guide for Diagnosis and Treatment of
      Laryngopharyngeal Reflux.
AB  - The study was under taken to know the prevalence of reflux signs in an
      individuals with throat complaints on the basis of reflux finding score (RFS) and
      quantitatively assess the effect of treatment. A cross-sectional study was done
      to evaluate the presence of laryngo-pharyngeal reflux signs in patients visiting
      ENT clinic with throat or voice problems in central India. There were 80 patients
      included in the study from 2017 to 2018 individuals. They were questioned
      regarding their symptoms. Their pharyngeal findings on rigid 70 degrees 
      laryngoscopy were viewed and RFS was made. The patients were reviewed at monthly
      intervals. Laryngopharyngeal reflux changes were seen in 36 of the 80 patients
      (45%). The reflux was graded as per the reflux finding score. The score ranged
      from 7 to maximum of 17 out of 26 in the patients with LPRD. Majority of the
      patients the score decreased with lifestyle changes and pantaprazole twice daily.
      There was poor response in 5% (4) patients, who were then advised to undergo
      upper gastro intestinal endoscopy for further assessment. Laryngopharyngeal
      reflux has become a very common entity in urban lifestyle. On careful examination
      the signs can be picked and assessed with the RFS, which is a very useful tool to
      grade and reassess patient on subsequent follow up.

PMID- 30211091
TI  - Robot Assisted Trans Axillary Thyroidectomy: A Subcontinent Experience.
AB  - To evaluate the outcome and initial hurdles of transaxillary robotic
      thyroidectomy in the Indian subcontinent. A total of seven (n = 7) patients were
      operated from August 2016 to February 2017. Ultrasonography was used as a tool to
      decide the size of thyroid lobe and fine needle aspiration cytology for the type
      of lesion. All patients underwent ipsilateral brachial plexus nerve conduction
      studies preoperatively. Two arm positions were evaluated. The robot was docked at
      the contralateral side of the surgical field. Before discharge from hospital, all
      patients were given a questionnaire evaluate outcome. Set 1 was answered on the
      day of discharge and Set 2 at one-month follow up. The most common pathology in
      our case series was colloid goiter (n = 4) followed by follicular lesion (n = 3).
      The mean console time was 167 min, with initial two cases taking more than 200
      min. The maximum and minimum length of the axillary tunnel was 16 and 27 cm
      respectively. There was no difference with regard to complication rate with
      either arm position. None of the patients developed brachial plexus injury and
      was confirmed by normal nerve conduction study done on postoperative day three.
      In our experience with transaxillary robotic thyroidectomy, the problems we faced
      in our population were unique considering the varied physical parameters. Use of
      malleable retractors comes handy in these situation and we recommend the use of
      these over the rigid ones. Though both the arm positions had similar outcomes,
      the one with sideways position was more favorable.

PMID- 30211092
TI  - Bell's Palsy-Tertiary Ischemia: An Etiological Factor in Residual Facial Palsy.
AB  - The facial nerve is unique among the motor nerves. It has long and tortuous
      course through the temporal bone and within the Fallopian canal. Because of this
      it is more prone to paralysis than any other nerve in the body. The most frequent
      type of facial palsy is Bell's palsy. This is an acute idiopathic lower motor
      neuron palsy of the facial nerve which does not normally progress and which is
      most usually unilateral and self limiting,: the majority of cases remit within 4
      6 months and nearly always remission is complete by 1 year. In those cases that
      do not recover it is my contention that this is caused by Either the progression,
      or after effects, of secondary ischemia: tertiary ischemia. In turn this causes
      thickening of the facial nerve sheath with a fibrous band or bands forming with
      resultant strangulation and compression of the nerve, which hampers its recovery.
      In such cases facial nerve decompression with slitting of the sheath and cutting
      of any fibrous bands would be the preferred management when allied with
      aggressive medical therapy.

PMID- 30211093
TI  - Neonatal Screening for Prevalence of Hearing Impairment in Rural Areas.
AB  - Hearing is one of the most important sense organs for man. Hearing loss is often
      associated with delayed speech and language development in young children. Early
      identification and intervention improves the chance a child gets to lesser delays
      in development and improving the overall quality of life. To find out the
      prevalence of hearing loss in neonates in the rural taluka of Maval, Pune,
      Maharashtra, India. Prospective Non Randomized Clinical Study. The study was
      carried out between April 2012 and April 2015. A total of 8192 babies were
      screened across various centers around the Maval area. The babies who had some
      high risk factors were 1683 in number and babies who had no high risk factors
      i.e. well babies were 6509. In our study, the overall prevalence of hearing loss
      in neonates in Maval taluka of Maharashtra was found to be 3.54 per 1000 live
      births, in normal born neonates (well babies) was 1.689 per 1000 births, in high
      risk babies was 10.69 per 1000 high risk births. The prevalence of low birth
      weight neonates, hyperbilirubinemia neonates and neonates with craniofacial
      abnormalities developing hearing impairment was found to be 5.9, 3.56 and 1.18
      per 1000 high risk births respectively. India is the second most populated
      country in the world with nearly a fifth of the world's population. There is a
      need for the universal neonatal screening for deafness for earlier detection of
      deafness and rehabilitation. Level of Evidence: Level IV.

PMID- 30211094
TI  - Spontaneous Medial Cribriform CSF Leak: Endoscopic Surgical Repair with Free
      Mucosal Graft-Our Experience.
AB  - Cribriform plate is the commonest site of spontaneous CSF leak, the fragility of
      the plate and juxtaposition of arachnoid's investment to the bone, where the
      olfactory nerve pierces the skull made this area, a vulnerable site for CSF leak.
      Transnasal endoscopic approach has gained popularity for CSF leak repair over the
      years. To describe the 5 year experience of spontaneous medial cribriform CSF
      leak repair with free mucosal graft in a tertiary medical centre. All patients
      who underwent transnasal endoscopic repair with free mucosal graft for
      spontaneous medial cribriform CSF leak in our institution between 2011 and 2016
      were reviewed. Twelve patients were identified, all were women with a mean age of
      44.5 years. The defect was localised by preoperative computed tomography scans
      with 1 mm cuts and MR cisternography. Via medial approach, the mucosa surrounding
      the entire defect was denuded and the defect was closed with free mucosal graft
      harvested either from the middle turbinate or from the nasal septum and middle
      turbinate was finally sutured with septum to stabilise the repair. The overall
      success rate was 100% with the first attempt with no recurrence or postoperative
      complications. Follow up ranged from 1 to 5 years. The endoscopic transnasal
      technique with free mucosal graft for the repair of spontaneous medial cribriform
      CSF rhinorrhoea is associated with a very high success rate and it should be
      considered for majority of cases.

PMID- 30211095
TI  - Treatment of Tympanic Membrane Retraction Pockets by Excision and Cartilage
      Tympanoplasty: A Prospective Study.
AB  - To assess the role of cartilage tympanoplasty in management of retraction pockets
      of the pars flaccida. This was a prospective study at a tertiary care centre.
      Twenty patients having grade III or grade IV retraction pockets were included in
      the study. Retraction pockets were treated by excision and cartilage
      tympanoplasty. Findings noted on follow-up were recorded and analysed. Graft was
      taken up in 18 (90%) cases with residual perforation in 2 (10%) cases. Recurrence
      of retraction pockets was observed in 6 (30%) cases. Hearing was improved up to
      15 dB in 16 (80%) cases. It is concluded that grade III and IV retraction pockets
      can be well managed by excision and cartilage tympanoplasty.

PMID- 30211096
TI  - Variations of Retromandibular Vein and Its Relation to Facial Nerve Within
      Parotid Gland.
AB  - Maxillary vein and superficial temporal vein unite to form the retromandibular
      vein in the parotid gland. The facial nerve lies lateral to external carotid
      artery and retromandibular vein. Identifying and preserving the facial nerve is
      the prime motto during parotidectomy. So the variations of facial nerve and the
      retromandibular vein should be known so as to avoid injury to both. The
      variations we encountered during parotid surgery will be helpful in avoiding
      unexpected bleeding and injury to facial nerve.

PMID- 30211097
TI  - Early Speech Perception Test Outcome in Children with Severe Sensorineural
      Hearing Loss with Unilateral Cochlear Implants Alone versus Bimodal Stimulation.
AB  - Bilateral stimulation of the auditory system has clear advantages over unilateral
      hearing. Hearing-impaired children are, therefore, generally fitted with hearing
      aids in both ears so that they can have the benefits of binaural hearing.
      Children who use acochlear implant in one ear and no acoustic stimulation in the
      opposite ear are at a definite disadvantage. This study was undertaken to
      determine the advantages of bimodal stimulation in pediatric population
      especially in terms of speech recognition. This study comprised of 30 children
      between 3 and 6 years of age with profound bilateral sensorineural hearing loss
      with cochlear implant in one ear and fitted with digital hearing aid in non
      implanted ear. Speech recognition performance was compared in unilateral cochlear
      implant only and with bimodal hearing stimulation in the same set of children. A
      statistically significant difference was found between speech reception scores in
      children with a unilateral cochlear implant only and those with a cochlear
      implant in one ear and a hearing aid in the non implanted ear in quiet
      surroundings. It is suggested that the use of bimodal fitting be considered as an
      effective management method to obtain the advantage of binaural hearing in
      children who undergo unilateral cochlear implantation.

PMID- 30211098
TI  - Association of Protein Expression p53 Mutants with Regional Lymph Gland Status on
      type III Carcinoma Nasofaring Patients.
AB  - Nasopharyngeal carcinoma (NPC) is a malignant disease originating from the
      nasopharyngeal epithelial cells. The molecular mechanism of cancer occurrence is
      a change in the oncogene and tumor suppressor genes. One of the tumor suppressor
      genes that mutate in cancer cells is the mutant p53 gene. One of nasopharyngeal
      carcinoma progression is determined by the status of regional lymph gland. The
      enormous regional lymph node has a poor prognosis. To analyze the expression of
      the mutant p53 protein in Nasopharyngeal carcinoma (NPC) that correlated with
      regional lymph gland status (N) as a clinical manifestation. Expression of mutant
      p53 protein from NPC tissue paraffin block with immunohistochemical cracking
      technique was using monoclonal rabbit Anti Human p53 clone 318-6-11 (Dako, North
      America, Inc., 6392 Via Real Carpinteria, CA 93013 USA), microscope light
      binoculars was assessed visually by an Anatomical Pathology Consultant. Positive
      expression of p53 mutants was obtained 57.58% from all the sample in N0 by 0
      subjects, N1 was 6 subjects, N2 was 7 subjects, and N3 was 7 subjects. The
      results of Mann-Whitney U test was p = 0.706, then there was no significant (p >
      0.05) correlation between positive expression of p53 protein in type III WHO NPC
      with the regional lymph gland were N0, N1, N2, and N3. There was no significant
      between expression protein p53 mutants' regional and lymph gland in type III WHO
      NPC.

PMID- 30211099
TI  - MRI as an Alternative to Second Look Mastoid Surgery.
AB  - The main goal of surgery of cholesteatoma is eradication of the disease and
      revision surgery is indicated when a dry and safe ear has not been achieved.
      Residual cholesteatoma usually occurs at the sites that are difficult to reach
      with an operating microscope, such as posterior tympanum and anterior epitympanic
      recess. Computed tomography can be performed to delineate the extent of disease.
      High-resolution computed tomography scanning is important for planning for
      surgery and is indicated for all revision mastoid operations. Magnetic resonance
      imaging is superior to computed tomography in tissue characterization for
      diagnosis of recurrent cholesteatoma. To evaluate the cases of recurrent
      cholesteatoma comparing the intraoperative surgical findings with the
      preoperative MRI radiological findings and if the preoperative MRI can replace
      the second look surgery for cholesteatoma. This study was applied on 60 patients
      that have a recurrent cholesteatoma after previous mastoid surgery. A
      preoperative radiological evaluation was done by Magnetic resonance, surgical
      management was done by canal wall up or canal wall down mastoidectomy to exclude
      residual disease. Then, radiological, and surgical findings correlation was done.
      Diffusion-weighted MRI successfully detected 42 cases out of the 45 cases of
      surgically proved cholesteatoma, it has accuracy 95%, sensitivity 93.33%,
      specificity 100%, PPV 100% and NPV 83.33%. MRI is better than CT in tissue
      characterization for diagnosis of recurrent cholesteatoma, and can replace the
      unnecessary second look surgery of cholesteatoma.

PMID- 30211100
TI  - Pectoralis Major Myocutaneous Flap Reconstruction for the Mandibular Defects in
      Advanced Oral Cavity Malignancies: A Retrospective Study of 30 Cases.
AB  - To evaluate the utility of the pectoralis major myocutaneous (PMMC) flap for the
      reconstruction of the mandible in advanced oral cavity malignancies in the Indian
      population. It was a retrospective study contained 30 patients with advanced oral
      cancer from July 2012 to August 2016. The PMMC reconstruction was done in all the
      patients to repair the bony defects in segmental/hemi mandibulectomy. The
      patients were followed up for a mean period of 6 months in the postoperative
      period and the utility of the PMMC flaps were evaluated. The mean age of the
      patients was 45 years (range 30-63 years). The average Karnofsky performance
      status score was 70 and majority of the patients had history of chronic medical
      illness. Of the 30 PMMC flaps, partial necrosis of the skin was noticed 2
      (06.66%) patients. Orocutaneous fistula was detected in 2 (06.66%) patient and 3
      (10%) patients presented with wound dehiscent in the immediate postoperative
      period. 3 (10%) patients had recurrence of the disease. PMMC flap can be a
      reliable option for advanced oral malignancies, especially in patients with poor
      status with the coexisting chronic illness. Due to the presence of a definite
      vascular pedicle, ease of harvesting the flap, quick surgical procedure, and the
      minimal postoperative morbidities, it can be considered as a valid alternative to
      the free flap to repair the bony defect, especially in patients with low
      socioeconomic corridor like India.

PMID- 30211101
TI  - Alteration of Serum Lipid in Oral Sub Mucous Fibrosis in Central India.
AB  - Oral sub mucous fibrosis is the most common precancerous lesion in India. Lipids
      are the major cell membrane components essential for various biological function
      including cell growth and division for the maintenance of cell integrity of
      normal and malignant tissue. Low levels of lipids serves as a marker and
      prognostic indicator in the early detection of oral precancerous and cancerous
      states. In spite of high prevalence and its potential to undergo malignant
      transformation, this condition has not widely been investigated with respect to
      serum lipid levels. In present study an attempt is made to analyze the complete
      serum profile, total cholesterol, triglycerides, high density lipoprotein. Low
      density lipoprotein, and very low density lipoprotein in oral precancerous lesion
      and control. Study was conducted in 30 clinically and histopathologically
      diagnosed cases of premalignant lesion and 30 age and sex match controls. The
      complete lipid profile including TC, TG, HDL, LDL, and VLDL was analyzed. Serum
      lipid levels were significantly lower in patients with oral lesion than in
      controls. From the finding it appears that the decreases in the lipid levels may
      be considered as useful marker in the early diagnosis of oral premalignant
      lesion.

PMID- 30211102
TI  - Distribution of Tryptophan Hydroxylase Immunoreactivity in the Spiral Ganglion
      Neurons of Mouse Cochlea.
AB  - Serotonin, also known as 5-hydroxytryptamine, is an important neurotransmitter
      and neuromodulator in the nervous system. Spiral ganglion neurons (SGNs) are the
      first station of the peripheral afferent auditory nervous system. We have
      previously demonstrated positive serotonin immunoreactivity in mouse SGNs.
      Whether serotonin in the SGNs is absorbed from the circumstances, or is
      synthesized by the neurons themselves is unknown. The purpose of this study was
      to find out the source of serotonin in the SGNs. Tryptophan hydroxylase is the
      rate-limiting enzyme in the process of serotonin biosynthesis. We detected
      tryptophan hydroxylase in the mouse SGNs using immunohistochemistry. The positive
      immunostaining of tryptophan hydroxylase was observed in the cytoplasm of SGNs.
      The cytoplasm of the SGNs was not get stained in the negative control group. Our
      results suggest that SGNs can synthesize serotonin themselves, and they may serve
      as an additional source of serotonin in the cochlea. The SGNs are serotonergic
      neurons. The receptors of serotonin on the membrane of SGNs interact with
      serotonin as auto-receptors. Serotonin in these neurons plays its physiological
      role in an autocrine/paracrine way.

PMID- 30211103
TI  - Role of Electronystagmography in Diagnosis of Secondary BPPV in Elderly Patients
      with Vertigo: A Retrospective Study.
AB  - Elderly population is frequently affected by vertigo which affects their mobility
      and makes them vulnerable to fall and other morbidities. Often these patient
      visit neurologist and are often subjected to CT scan, MRI brain etc. to rule out
      a central cause of vertigo; whereas majority of these patients suffer from
      vestibular cause of vertigo. A schematic approach by detailed history, simple
      tests for vestibular functions like Dix Hallpike, supine roll and head impulse
      test give important clue to diagnosis. Often the diagnosis is benign paroxysmal
      positional vertigo (BPPV) which is treated by repositioning maneuver. There are
      often other vestibular causes which may be diagnosed by Electronystagmography
      (ENG), electrocochleography and other tests. This study was undertaken to study
      occurrence of secondary BPPV utilizing various parameters of ENG. The study group
      comprised of 131 patients from the neuro-otology proforma data base at ENT centre
      and vertigo clinic from January 2015 to December 2017. Inclusion criterion was
      male and female aged 51 years and above presenting with dizziness, imbalance,
      rotational vertigo, unsteadiness as the chief complaint. Exclusion criterion was
      BPPV relieved after Epley's maneuver, Otitis externa, acute Otitis media,
      Suppurative Otitis media, pre existing neurological condition and history of ear
      surgery. Neuro-otology Data obtained and the ENG findings were tabulated in the
      master chart and the observations interpreted and transferred to Claussen's
      butterfly chart. The study group comprised of 58 male (44.27%) and 73 female
      (55.73%) with a male female ratio of 1:1.25. ENG exhibited 36 patients (27.49) to
      have recurrent BPPV, 53 (40.45%) were found to have unilateral/bilateral canal
      paresis. Meniere's disease was diagnosed in 39 (29.77%) patients and brain stem
      pathology identified in 3 (2.29%) cases.

PMID- 30211104
TI  - Sternocleidomastoid Flap in Parotid Surgery: A Case Series.
AB  - Superficial and deep parotidectomies are known treatments for benign and
      malignant neoplasms of parotid glands. Due to the gland's proximity to facial
      nerve and other vital structures, this surgery carries the highest risk of facial
      nerve palsy. Another frequently overlooked complication, which can be detrimental
      to patient's life style is Frey's syndrome, or gustatory sweating. Other
      complications include flap necrosis and various contour deformities. We conducted
      this study on a group of 40 patients of parotid swellings to assess usage of
      sternocleidomastoid flap in prevention of Frey's syndrome, contour deformities,
      flap necrosis, salivary fistula and drain related injuries. We divided the
      patients in two groups based on the usage of sternomastoid flap. In Group A, the
      patients underwent superficial or total parotidectomies with a partial thickness,
      superiorly based sternomastoid flap. In Group B, no sternomastoid flap was
      placed. The incidence of Frey's syndrome was seen to be 3 times in Group B, while
      a visible contour deformity was seen in a third of patients in Group B, with
      Group A reporting no incidence. Also Group A, did not see any cases of flap
      necrosis or salivary fistula, while Group B saw 3 and 2 cases respectively. Also,
      among the two revision cases done in Group A, the one with previously placed
      sternomastoid flap (done by us 3 years back) had an excellent plane preserved,
      while another revision case without sternomastoid flap saw a complete adherence
      of facial nerve to overlying skin, resulting in Grade II permanent facial palsy.
      Parotidectomy is a technically challenging surgery in regards to important
      structures in the vicinity. Even with ostensibly perfect technique, facial nerve
      injury can occur for unknown reasons. All in all, sternomastoid flap is an
      acceptable modality to fill the parotidectomy defect, improve the facial contour
      and reduce the incidences of Frey's syndrome and skin necrosis.

PMID- 30211106
TI  - Stapes Surgery Teaching Tool: A Simple and Stable Technique.
AB  - Stapedotomy followed by placement of a piston prosthesis is the mainstay for
      surgical management of otosclerosis primarily undertaken to improve hearing in
      patients. Although a simple and elegant procedure, prosthesis placement in stapes
      surgery is difficult to master. Improper surgical technique or improper placement
      of prosthesis may result in complications which may require revision surgery. We
      here describe a training technique that is simple, inexpensive, improves the
      skills and can be done using easily available materials such as a disposable
      syringe, stapler pin and micro-forceps. Regular practice with this training
      module minimizes surgical time and can even be done just prior to the surgery,
      however, this is not a substitute for temporal bone dissections.

PMID- 30211107
TI  - Pleomorphic Adenoma (Mixed Tumor) of Dorsum of Nose: A Rare Tumor at a Rare Site.

PMID- 30211105
TI  - A Clinical Study of Effect of Hyperpyrexia on Otoacoustic Emissions in Children.
AB  - Various degrees of sensory neural hearing loss can be seen in the progression of
      some hereditary periodic fever syndromes. Otoacoustic emission testing can help
      to establish the inner ear involvement at an early period of a periodic fever
      with a risk of hearing loss (Abdul Kadir et al. in J Int Adv Otol 9(2.79):08-11,
      2014). Sensorineural hearing loss is the common most complication of bacterial
      meningitis in childhood (Richardson in Pediatrics 102(6):1364-1368, 1998). When
      present from birth, or acquired in the pre-school years, hearing loss of any
      degree, even mild hearing loss, interferes with speech and language development.
      In addition to obvious communication deficits, the consequences of hearing loss
      in children and adults include psychosocial problems, such as frustration,
      irritability, anxiety, the tendency to withdraw from social interactions, and
      even depression (Dhar and Hall in Otoacoustic emissions: principles, procedures,
      and protocols, Plural Publishing, San Diego, 2011). OAE are acoustic signals
      emitted from cochlea to the middle ear and into the external ear where they are
      recorded. Evoked OAE are undetectable when deafness is above 30-35 dB Sound
      pressure level (Biswas in Clinical audio-vestibulometry for otologists and
      neurologists, Bhalani Publishing House, Mumbai, 1995). OAEs permit early
      detection of inner ear abnormalities associated with a wide variety of diseases
      and disorders, including Alport syndrome etc. With early detection, the serious
      consequences of hearing loss can sometimes be prevented. With proper
      identification and diagnosis of hearing impairment, timely and effective
      management for the same can be taken. Data for this study was collected from
      children (5-14 years) attending the Department of Otorhinolaryngology and
      Paediatrics Out-patient departments in P.E.S.I.M.S.R, Kuppam. Among the study
      population 43 (57.3%) were male and 32 (42.7%) were females showing the slight
      male preponderance. study was done on children with temperature > 1000 F,
      children with temperature were screened with OAE, and OAE was recorded in same
      children once fever has subsided and results were compared. This is a new study
      where we compared same group of children with fever and once fever has subsided.
      In most other studies, study group was compared to the healthy control group. In
      our study, children with fever having abnormal FDP values at f1were 9, they
      reverted back to base line once fever has subsided. This shows that there is no
      much damage to inner ear at lower frequencies. Almost 47 abnormal FDP values at
      f2 reverted back to normal. At higher frequencies (f3 and f4), there is no much
      change in abnormal FDPs with fever and after fever has subsided, this shows that
      there is more damage to inner ear at higher frequencies. This study demonstrated
      that hyperpyrexia causes hearing loss in children with fever probably due to
      cochlear involvement. We conclude that OAE can be used as a screening tool in
      detecting hearing loss among children because the technique is simple,
      reproducible, not expensive, not time consuming also effectively narrows down the
      children with high chances of hearing loss thereby effectively improves the
      chances of early diagnosis and hence children can be rehabilitated early, making
      a marked change in their future.

PMID- 30211108
TI  - Small Cell Neuroendocrine Carcinoma: A Rare Nasopharyngeal Malignancy with
      Aggressive Clinical Course.
AB  - Primary small cell neuroendocrine carcinoma is uncommon in head and neck region,
      with occasional cases in nasopharynx. Distinction from other round cell tumors is
      imperative to ensure optimal patient management. We present a case of a 30-year
      old woman who presented with a rapidly growing nasopharyngeal mass.

PMID- 30211109
TI  - A Rare Case of Adenoid Cystic Carcinoma of the Sphenoid Sinus Presenting with
      Lateral Rectus Palsy.
AB  - A rare case of adenoid cystic carcinoma arising from the sphenoid sinus causing
      lateral rectus palsy is presented here. Adenoid cystic carcinoma of the paranasal
      sinuses is an aggressive neoplasm which needs early diagnosis and treatment.
      Ideal treatment paradigm for paranasal sinus tumors is yet to be established. A
      combination of surgery and radiotherapy offers a better disease control and
      survival.

PMID- 30211110
TI  - Cell-Free DNA Profiling to Discover Mechanisms of Exceptional Response to
      Cabozantinib Plus Panitumumab in a Patient With Treatment Refractory Metastatic
      Colorectal Cancer.
AB  - MET amplification is rare in treatment-naive metastatic colorectal cancer (CRC)
      tumors, but can emerge as a mechanism of resistance to anti-EGFR therapies.
      Preclinical and clinical data suggest that patients with MET amplified tumors
      benefit from MET-targeted therapy. Cabozantinib is an inhibitor of multiple
      tyrosine kinases, included c-MET. Panitumumab is an inhibitor of EGFR. This
      report describes a patient with KRAS, NRAS, and BRAF wild-type metastatic CRC who
      experienced disease progression on all standard chemotherapy and anti-EGFR
      antibody therapy. The patient was enrolled in a clinical trial evaluating the
      combination of cabozantinib plus panitumumab. After only 6 weeks of treatment,
      the patient experienced a significant anti-tumor response. Although tumor tissue
      was negative for MET amplification, molecular profiling of cell-free DNA (cfDNA)
      revealed MET amplification. This case represents the first report showing the
      activity of cabozantinib in combination with panitumumab in a patient with
      metastatic CRC, and suggests that MET amplification in cfDNA may be a biomarker
      of response. A clinical trial targeting MET amplified metastatic CRC is currently
      underway.

PMID- 30211112
TI  - Applying an Exposome-Wide (ExWAS) Approach to Cancer Research.
AB  - Traditional research approaches, including genome-wide association studies
      (GWAS), epigenome-wide association studies (EWAS) and Gene * Environment (G * E)
      studies are limited in their ability to handle the multiplicity of chemical and
      non-chemical toxicants to which people are exposed in the real world, over their
      life course, their impact on epigenomics and other biological systems, and their
      relationship to cancer onset, progression, and outcomes. Exposome-wide
      association study (ExWAS) provides a new approach for conceptualizing the roles
      and relationships of multiple chemical and non-chemical exposures in the etiology
      and progression of cancer at key developmental periods, over the life course, and
      across generations. ExWAS challenges us to consider the influence of both
      internal and external environment, chemical and non-chemical stressors, risk and
      protective factors, and spatial and temporal dimensions of exposures in our
      models of cancer incidence, outcomes, and disparities. Applying an ExWAS approach
      to cancer and cancer disparities research supports robust computational models
      and methods that will allow for analysis of the dynamic and complex interactions
      between genetics, epigenetics, and exposomics factors. In the coming months, we
      will spatially and temporally align environmental exposures with SCCS participant
      data from time of enrollment forward to move us closer to identifying complete
      exposure pathways that lead to cancer. In the future, we hope to link external
      sources of exposure to biomarkers of exposure, biomarkers of disease, disease
      phenotypes, and population level disparities.

PMID- 30211111
TI  - Immune Checkpoint Inhibition in Head and Neck Cancer.
AB  - Head and Neck Squamous Cell Carcinoma (HNSCC) is the 6th most common cancer
      globally and commonly presents with locally advanced disease, which has a
      recurrence rate of around 50% despite aggressive multi-modality treatment
      involving surgery, radiotherapy and chemotherapy or EGFR inhibition where
      appropriate. As understanding of the underlying cancer biology and the complex
      interactions within the tumor microenvironment improves, there is gathering
      interest in and evidence for the role of immunomodulating agents in the
      management of HNSCC. Immune checkpoint inhibitors, which aim to hinder the
      inhibitory interaction between programmed cell death protein 1 (PD-1) and its
      ligand PD-L1, have demonstrated durable improvements in patient outcomes in
      advanced / metastatic HNSCC, with both pembrolizumab and nivolumab being granted
      FDA approval in 2016. There are numerous ongoing clinical trials exploring the
      role of checkpoint inhibitors both as single agents and in combination,
      administered with established treatment modalities such as chemotherapy and
      radiotherapy, as well as alongside other novel immune modulators. These trials
      are not limited to advanced / metastatic HNSCC, but also to the neo-adjuvant or
      adjuvant settings. As studies complete and more results become available, the
      role immunotherapy agents will have within the treatment strategies for HNSCC may
      change, with increasing biomarker selection resulting in personalized therapy
      aiming to further improve patient outcomes.

PMID- 30211113
TI  - Immunomodulation Mediated by Anti-angiogenic Therapy Improves CD8 T Cell Immunity
      Against Experimental Glioma.
AB  - Glioblastoma (GBM) is a lethal cancer of the central nervous system with a median
      survival rate of 15 months with treatment. Thus, there is a critical need to
      develop novel therapies for GBM. Immunotherapy is emerging as a promising
      therapeutic strategy. However, current therapies for GBM, in particular anti
      angiogenic therapies that block vascular endothelial growth factor (VEGF), may
      have undefined consequences on the efficacy of immunotherapy. While this
      treatment is primarily prescribed to reduce tumor vascularization, multiple
      immune cell types also express VEGF receptors, including the most potent antigen
      presenting cell, the dendritic cell (DC). Therefore, we assessed the role of anti
      VEGF therapy in modifying DC function. We found that VEGF blockade results in a
      more mature DC phenotype in the brain, as demonstrated by an increase in the
      expression of the co-stimulatory molecules B7-1, B7-2, and MHC II. Furthermore,
      we observed reduced levels of the exhaustion markers PD-1 and Tim-3 on brain
      infiltrating CD8 T cells, indicating improved functionality. Thus, anti
      angiogenic therapy has the potential to be used in conjunction with and enhance
      immunotherapy for GBM.

PMID- 30211114
TI  - Monocarboxylate Transporter 4 (MCT4) Knockout Mice Have Attenuated 4NQO Induced
      Carcinogenesis; A Role for MCT4 in Driving Oral Squamous Cell Cancer.
AB  - Head and neck squamous cell carcinoma (HNSCC) is the 6th most common human cancer
      and affects approximately 50,000 new patients every year in the US. The major
      risk factors for HNSCC are tobacco and alcohol consumption as well as oncogenic
      HPV infections. Despite advances in therapy, the overall survival rate for all
      comers is only 50%. Understanding the biology of HNSCC is crucial to identifying
      new biomarkers, implementing early diagnostic approaches and developing novel
      therapies. As in several other cancers, HNSCC expresses elevated levels of MCT4,
      a member of the SLC16 family of monocarboxylate transporters. MCT4 is a H+-linked
      lactate transporter which functions to facilitate lactate efflux from highly
      glycolytic cells. High MCT4 levels in HNSCC have been associated with poor
      prognosis, but the role of MCT4 in the development and progression of this cancer
      is still poorly understood. In this study, we used 4-nitroquinoline-1-oxide
      (4NQO) to induce oral cancer in MCT4-/- and wild type littermates, recapitulating
      the disease progression in humans. Histological analysis of mouse tongues after
      23 weeks of 4NQO treatment showed that MCT4-/- mice developed significantly fewer
      and less extended invasive lesions than wild type. In mice, as in human samples,
      MCT4 was not expressed in normal oral mucosa but was detected in the transformed
      epithelium. In the 4NQO treated mice we detected MCT4 in foci of the basal layer
      undergoing transformation, and progressively in areas of carcinoma in situ and
      invasive carcinomas. Moreover, we found MCT4 positive macrophages within the
      tumor and in the stroma surrounding the lesions in both human samples of HNSCC
      and in the 4NQO treated animals. The results of our studies showed that MCT4
      could be used as an early diagnostic biomarker of HNSCC. Our finding with the
      MCT4-/- mice suggest MCT4 is a driver of progression to oral squamous cell cancer
      and MCT4 inhibitors could have clinical benefits for preventing invasive HNSCC.

PMID- 30211116
TI  - Re-purposing Chloroquine for Glioblastoma: Potential Merits and Confounding
      Variables.
AB  - There is a growing evidence that antimalarial chloroquine could be re-purposed
      for cancer treatment. A dozen of clinical trials have been initiated within the
      past 10 years to test the potential of chloroquine as an adjuvant treatment for
      therapy-refractory cancers including glioblastoma, one of the most aggressive
      human cancers. While there is considerable evidence for the efficacy and safety
      of chloroquine the mechanisms underlying the tumor suppressive actions of this
      drug remain elusive. Up until recently, inhibition of the late stage of autophagy
      was thought to be the major mechanism of chloroquine-mediated cancer cells death.
      However, recent research provided compelling evidence that autophagy-inhibiting
      activities of chloroquine are dispensable for its ability to suppress tumor cells
      growth. These unexpected findings necessitate a further elucidation of the
      molecular mechanisms that are essential for anti-cancer activities of CHQ. This
      review discusses the versatile actions of chloroquine in cancer cells with
      particular focus on glioma cells.

PMID- 30211118
TI  - Paclitaxel Plus Cetuximab as 1st Line Chemotherapy in Platinum-Based
      Chemoradiotherapy-Refractory Patients With Squamous Cell Carcinoma of the Head
      and Neck.
AB  - Purpose: We sought to evaluate the efficacy and safety of the combination of
      cetuximab (Cmab) and paclitaxel (PTX) in patients with squamous cell carcinoma of
      the head and neck (SCCHN) who had unresectable recurrent or metastatic (R/M)
      disease after platinum-based chemoradiotherapy. Materials and Methods: Data on 23
      patients with SCCHN who received paclitaxel and cetuximab (Cmab) for R/M disease
      no more than 6 months after CRT completion were retrospectively reviewed. PTX and
      Cmab were given in a 28-day cycle (PTX, 80 mg/m2 on days 1, 8, and 15; Cmab,
      loading dose 400 mg/m2 followed by a weekly 250 mg/m2). The differences in
      prognosis between subgroups in different clinical settings were also assessed.
      Results: CRT had been delivered as definitive treatment in 13 cases (57%) and as
      adjuvant treatment in 10 (43%). Median time from CRT completion to disease
      recurrence or metastasis was 73 days (1-152). The best objective response and
      disease control rates were 52 and 83%, respectively, with 12 partial responses
      and seven cases of stable disease by Response Evaluation Criteria in Solid Tumors
      (RECIST). A total of 17 of 23 patients (74%) achieved a degree of tumor
      shrinkage. Median progression-free survival (PFS) and overall survival (OS) were
      7.0 (95% confidence interval [CI]: 3.7-8.4) and 16.3 months (95% CI: 7.8-23.3),
      respectively. Patients with a longer duration (>=60 d) from CRT completion to
      disease progression had a statistically significantly longer OS than the others
      (median OS 22.3 vs. 8.1 months, log-rank test; p = 0.034). Main Grade 3
      toxicities included neutropenia (13%), anemia (13%), and hypomagnesemia (13%). No
      Grade 4 toxicity or treatment-related death was seen. Conclusion: PTX and Cmab is
      a tolerable and effective option in SCCHN patients with symptomatic CRT
      refractory disease. Its favorable effects on tumor shrinkage will help relieve
      tumor-associated symptoms.

PMID- 30211117
TI  - Low-Intensity MR-Guided Focused Ultrasound Mediated Disruption of the Blood-Brain
      Barrier for Intracranial Metastatic Diseases.
AB  - Low-intensity MR-guided focused ultrasound in combination with intravenously
      injected microbubbles is a promising platform for drug delivery to the central
      nervous system past the blood-brain barrier. The blood-brain barrier is a key
      bottleneck for cancer therapeutics via limited inter- and intracellular
      transport. Further, drugs that cross the blood-brain barrier when delivered in a
      spatially nonspecific way, result in adverse effects on normal brain tissue, or
      at high concentrations, result in increasing risks to peripheral organs. As such,
      various anti-cancer drugs that have been developed or to be developed in the
      future would benefit from a noninvasive, temporary, and repeatable method of
      targeted opening of the blood-brain barrier to treat metastatic brain diseases.
      MR-guided focused ultrasound is a potential solution to these design
      requirements. The safety, feasibility and preliminary efficacy of MRgFUS aided
      delivery have been demonstrated in various animal models. In this review, we
      discuss this preclinical evidence, mechanisms of focused ultrasound mediated
      blood-brain barrier opening, and translational efforts to neuro-oncology
      patients.

PMID- 30211119
TI  - The Mouse Hospital and Its Integration in Ultra-Precision Approaches to Cancer
      Care.
AB  - Precision medicine holds real promise for the treatment of cancer. Adapting
      therapeutic strategies so patients receive individualized treatment protocols,
      will transform how diseases like cancer are managed. Already, molecular profiling
      technologies have provided unprecedented capacity to characterize tumors, yet the
      ability to translate this to actionable outcome in the clinic is limited. To
      enable real time translation of personalized therapeutic approaches to patient
      care in a co-clinical manner will require the adoption and integration of
      approaches that facilitate modeling of patient disease. The Mouse Hospital
      represents an approach that is ideally suited to pre- and co-clinical evaluation
      of novel therapeutic strategies for clinical care. Patient derived xenograft
      (PDX) technologies and in situ tumor modeling approaches using genetically
      engineered mouse models (GEMMs) already have a proven capacity to mimic human
      tumor responses, and their application can deliver invaluable insights into
      appropriate clinical approaches for individual patients by mirroring human
      clinical trials using a Co-Clinical Trial project and Mouse Hospital
      infrastructure. Additionally, the integration of the Mouse Hospital with other
      emerging technologies for the application of precision medicines, including
      organoid technologies, provides a platform that enables medical centers to truly
      reap the benefits that precision medicine has to offer.

PMID- 30211121
TI  - Low-Level Laser Therapy Stimulates Proliferation in Head and Neck Squamous Cell
      Carcinoma Cells.
AB  - Objectives: Low-level laser therapy (LLLT) is a promising non-invasive treatment
      option for oropharyngeal mucositis, which is a common side effect of many
      oncological treatments. LLLT is known for its wound healing properties due to the
      stimulation of cellular processes, such as proliferation, migration and
      differentiation. Controversy exists on the possible stimulatory effect of LLLT on
      head and neck cancer (HNSCC) cells in patients treated with radiotherapy. The aim
      of this study was to evaluate the biostimulatory effect together with the
      underlying mechanisms of LLLT on HNSCC cancer cells and normal epithelial cells.
      Materials and methods: HNSCC cell lines (SCC154, SQD9, and SCC61) and human
      tonsil epithelial cells were exposed to a Gallium-Aluminum-Arsenide diode laser
      (830 nm, 150 mW) with energy densities of 0, 1, and 2 J/cm2. The proliferation
      potential of the cells was assessed by Sulforhodamine B assay, immunoblotting
      (mitogenic pathways), immunocytochemistry (Ki67), and flow cytometry (PI cell
      cycle staining). Results: Cell proliferation was increased in HNSCC cell lines
      after laser irradiation with 1 J/cm2, whereas no significant increase was seen
      after laser irradiation with 2 J/cm2. In contrast, no effect on cell
      proliferation was seen in the human tonsil epithelial cells after laser
      irradiation with any of the energy densities. The increased proliferation was
      associated with elevated levels of pAKT, pERK, and Ki67 protein expression and
      cell cycle progression. Conclusion: Our results show that LLLT increases cell
      proliferation in a dose-dependent manner in HNSCC cells but not in normal
      epithelial tonsil cells. These results suggest that LLLT has to be used with
      caution when treating oropharyngeal mucositis in HNSCC patients since tumor cells
      present in the LLLT irradiation field could be triggered by LLLT.

PMID- 30211120
TI  - Metformin as a Therapeutic Target in Endometrial Cancers.
AB  - Endometrial cancer is the most common gynecologic malignancy in developed
      countries. Its increasing incidence is thought to be related in part to the rise
      of metabolic syndrome, which has been shown to be a risk factor for the
      development of hyperestrogenic and hyperinsulinemic states. This has consequently
      lead to an increase in other hormone-responsive cancers as well e.g., breast and
      ovarian cancer. The correlation between obesity, hyperglycemia, and endometrial
      cancer has highlighted the important role of metabolism in cancer establishment
      and persistence. Tumor-mediated reprogramming of the microenvironment and
      macroenvironment can range from induction of cytokines and growth factors to
      stimulation of surrounding stromal cells to produce energy-rich catabolites,
      fueling the growth, and survival of cancer cells. Such mechanisms raise the
      prospect of the metabolic microenvironment itself as a viable target for
      treatment of malignancies. Metformin is a biguanide drug that is a first-line
      treatment for type 2 diabetes that has beneficial effects on various markers of
      the metabolic syndrome. Many studies suggest that metformin shows potential as an
      adjuvant treatment for uterine and other cancers. Here, we review the evidence
      for metformin as a treatment for cancers of the endometrium. We discuss the
      available clinical data and the molecular mechanisms by which it may exert its
      effects, with a focus on how it may alter the tumor microenvironment. The
      pleiotropic effects of metformin on cellular energy production and usage as well
      as intercellular and hormone-based interactions make it a promising candidate for
      reprogramming of the cancer ecosystem. This, along with other treatments aimed at
      targeting tumor metabolic pathways, may lead to novel treatment strategies for
      endometrial cancer.

PMID- 30211122
TI  - Intercellular Communication in Tumor Biology: A Role for Mitochondrial Transfer.
AB  - Intercellular communication between cancer cells and other cells in the tumor
      microenvironment plays a defining role in tumor development. Tumors contain
      infiltrates of stromal cells and immune cells that can either promote or inhibit
      tumor growth, depending on the cytokine/chemokine milieu of the tumor
      microenvironment and their effect on cell activation status. Recent research has
      shown that stromal cells can also affect tumor growth through the donation of
      mitochondria to respiration-deficient tumor cells, restoring normal respiration.
      Nuclear and mitochondrial DNA mutations affecting mitochondrial respiration lead
      to some level of respiratory incompetence, forcing cells to generate more energy
      by glycolysis. Highly glycolytic cancer cells tend to be very aggressive and
      invasive with poor patient prognosis. However, purely glycolytic cancer cells
      devoid of mitochondrial DNA cannot form tumors unless they acquire mitochondrial
      DNA from adjacent cells. This perspective article will address this apparent
      conundrum of highly glycolytic cells and cover aspects of intercellular
      communication between tumor cells and cells of the microenvironment with
      particular emphasis on intercellular mitochondrial transfer.

PMID- 30211123
TI  - WWOX Tumor Suppressor Gene in Breast Cancer, a Historical Perspective and Future
      Directions.
AB  - The WWOX tumor suppressor gene is located at 16q23. 1-23.2, which covers the
      region of FRA16D-a common fragile sites. Deletions within the WWOX coding
      sequence are observed in up to 80% of breast cancer cases, which makes it one of
      the most common genetic alterations in this tumor type. The WWOX gene is known to
      play a role in breast cancer: increased expression of WWOX inhibits cell
      proliferation in suspension, reduces tumor growth rates in xenographic
      transplants, but also enhances cell migration through the basal membrane and
      contributes to morphological changes in 3D matrix-based cell cultures. The WWOX
      protein may act in several ways, as it has three functional domains-two WW
      domains, responsible for protein-protein interactions and an SDR domain (short
      dehydrogenase/reductase domain) which catalyzes conversions of low molecular
      weight ligands, most likely steroids. In epithelial cells, WWOX modulates gene
      transcription through interaction with p73, AP-2gamma, and ERBB4 proteins. In
      steroid hormone-regulated tissues like mammary gland epithelium, the WWOX SDR
      domain acts as a steroid dehydrogenase. The relationship between WWOX and hormone
      receptors was shown in an animal model, where WWOX(C3H)+/-mice exhibited loss of
      both ER and PR receptors. Moreover, in breast cancer specimens, a positive
      correlation was observed between WWOX expression and ER status. On the other
      hand, decreased WWOX expression was associated with worse prognosis, namely
      higher relapse and mortality rates in BC patients. Recently, it was shown that
      genomic instability might be driven by the loss of WWOX expression. It was
      reported that WWOX plays role in DNA damage response (DDR) and DNA repair by
      regulating ATM activation through physical interaction. A genome caretaker
      function has also been proposed for WWOX, as it was found that WWOX sufficiency
      decreases homology directed repair (HDR) and supports non-homologous end-joining
      (NHEJ) repair as the dominant DSB repair pathway by Brca1-Wwox interaction. In
      breast cancer cells, WWOX was also found to modulate the expression of glycolysis
      pathway genes, through hypoxia-inducible transcription factor 1alpha (HIF1alpha)
      regulation. The paper presents the current state of knowledge regarding the WWOX
      tumor suppressor gene in breast cancer, as well as future research perspectives.

PMID- 30211125
TI  - Comparative Evolution of Sand Fly Salivary Protein Families and Implications for
      Biomarkers of Vector Exposure and Salivary Vaccine Candidates.
AB  - Sand fly salivary proteins that produce a specific antibody response in humans
      and animal reservoirs have been shown to be promising biomarkers of sand fly
      exposure. Furthermore, immunity to sand fly salivary proteins were shown to
      protect rodents and non-human primates against Leishmania infection. We are
      missing critical information regarding the divergence amongst sand fly salivary
      proteins from different sand fly vectors, a knowledge that will support the
      search of broad or specific salivary biomarkers of vector exposure and those for
      vaccines components against leishmaniasis. Here, we compare the molecular
      evolution of the salivary protein families in New World and Old World sand flies
      from 14 different sand fly vectors. We found that the protein families unique to
      OW sand flies are more conserved than those unique to NW sand flies regarding
      both sequence polymorphisms and copy number variation. In addition, the protein
      families unique to OW sand flies do not display as many conserved cysteine
      residues as the one unique to the NW group (28.5% in OW vs. 62.5% in NW).
      Moreover, the expression of specific protein families is restricted to the
      salivary glands of unique sand fly taxon. For instance, the ParSP15 family is
      unique to the Larroussius subgenus whereas phospholipase A2 is only expressed in
      member of Larroussius and Adlerius subgenera. The SP2.5-like family is only
      expressed in members of the Phlebotomus and Paraphlebotomus subgenera. The
      sequences shared between OW and NW sand flies have diverged at similar rates
      (38.7 and 45.3% amino acid divergence, respectively), yet differences in gene
      copy number were evident across protein families and sand fly species. Overall,
      this comparative analysis sheds light on the different modes of sand fly salivary
      protein family divergence. Also, it informs which protein families are unique and
      conserved within taxon for the choice of taxon-specific biomarkers of vector
      exposure, as well as those families more conserved across taxa to be used as pan
      specific vaccines for leishmaniasis.

PMID- 30211115
TI  - The Network of Non-coding RNAs in Cancer Drug Resistance.
AB  - Non-coding RNAs (ncRNAs) have been implicated in most cellular functions. The
      disruption of their function through somatic mutations, genomic imprinting,
      transcriptional and post-transcriptional regulation, plays an ever-increasing
      role in cancer development. ncRNAs, including notorious microRNAs, have been thus
      proposed to function as tumor suppressors or oncogenes, often in a context
      dependent fashion. In parallel, ncRNAs with altered expression in cancer have
      been reported to exert a key role in determining drug sensitivity or restoring
      drug responsiveness in resistant cells. Acquisition of resistance to anti-cancer
      drugs is a major hindrance to effective chemotherapy and is one of the most
      important causes of relapse and mortality in cancer patients. For these reasons,
      non-coding RNAs have become recent focuses as prognostic agents and modifiers of
      chemo-sensitivity. This review starts with a brief outline of the role of most
      studied non-coding RNAs in cancer and then highlights the modulation of cancer
      drug resistance via known ncRNAs based mechanisms. We identified from literature
      388 ncRNA-drugs interactions and analyzed them using an unsupervised approach.
      Essentially, we performed a network analysis of the non-coding RNAs with direct
      relations with cancer drugs. Within such a machine-learning framework we detected
      the most representative ncRNAs-drug associations and groups. We finally discussed
      the higher integration of the drug-ncRNA clusters with the goal of disentangling
      effectors from downstream effects and further clarify the involvement of ncRNAs
      in the cellular mechanisms underlying resistance to cancer treatments.

PMID- 30211124
TI  - Sphere-Formation Assay: Three-Dimensional in vitro Culturing of Prostate Cancer
      Stem/Progenitor Sphere-Forming Cells.
AB  - Cancer Stem Cells (CSCs) are a sub-population of cells, identified in most
      tumors, responsible for the initiation, recurrence, metastatic potential, and
      resistance of different malignancies. In prostate cancer (PCa), CSCs were
      identified and thought to be responsible for the generation of the lethal
      subtype, commonly known as Castration-Resistant Prostate Cancer (CRPC). In vitro
      models to investigate the properties of CSCs in PCa are highly required. Sphere
      formation assay is an in vitro method commonly used to identify CSCs and study
      their properties. Here, we report the detailed methodology on how to generate and
      propagate spheres from PCa cell lines and from murine prostate tissue. This model
      is based on the ability of stem cells to grow in non-adherent serum-free gel
      matrix. We also describe how to use these spheres in histological and immuno
      fluorescent staining assays to assess the differentiation potential of the CSCs.
      Our results show the sphere-formation Assay (SFA) as a reliable in vitro assay to
      assess the presence and self-renewal ability of CSCs in different PCa models.
      This platform presents a useful tool to evaluate the effect of conventional or
      novel agents on the initiation and self-renewing properties of different tumors.
      The effects can be directly evaluated through assessment of the sphere-forming
      efficiency (SFE) over five generations or other downstream assays such as immuno
      histochemical analysis of the generated spheres.

PMID- 30211127
TI  - Antibiofilm and Antivirulence Activities of 6-Gingerol and 6-Shogaol Against
      Candida albicans Due to Hyphal Inhibition.
AB  - Candida albicans is an opportunistic pathogen and responsible for candidiasis. C.
      albicans readily forms biofilms on various biotic and abiotic surfaces, and these
      biofilms can cause local and systemic infections. C. albicans biofilms are more
      resistant than its free yeast to antifungal agents and less affected by host
      immune responses. Transition of yeast cells to hyphal cells is required for
      biofilm formation and is believed to be a crucial virulence factor. In this
      study, six components of ginger were investigated for antibiofilm and
      antivirulence activities against a fluconazole-resistant C. albicans strain. It
      was found 6-gingerol, 8-gingerol, and 6-shogaol effectively inhibited biofilm
      formation. In particular, 6-shogaol at 10 MUg/ml significantly reduced C.
      albicans biofilm formation but had no effect on planktonic cell growth. Also, 6
      gingerol and 6-shogaol inhibited hyphal growth in embedded colonies and free
      living planktonic cells, and prevented cell aggregation. Furthermore, 6-gingerol
      and 6-shogaol reduced C. albicans virulence in a nematode infection model without
      causing toxicity at the tested concentrations. Transcriptomic analysis using RNA
      seq and qRT-PCR showed 6-gingerol and 6-shogaol induced several transporters
      (CDR1, CDR2, and RTA3), but repressed the expressions of several hypha/biofilm
      related genes (ECE1 and HWP1), which supported observed phenotypic changes. These
      results highlight the antibiofilm and antivirulence activities of the ginger
      components, 6-gingerol and 6-shogaol, against a drug resistant C. albicans
      strain.

PMID- 30211126
TI  - Polarized Entry of Human Parechoviruses in the Airway Epithelium.
AB  - Human parechoviruses (HPeVs), a poorly studied genus within the Picornaviridae
      family, are classified into 19 genotypes of which HPeV1 and HPeV3 are the most
      often detected. HPeV1 VP1 C terminus contains an arginine-glycine-aspartic acid
      (RGD) motif and has been shown to depend on the host cell surface alphaV
      integrins (alphaV ITGs) and heparan sulfate (HS) for entry. HPeV3 lacks this
      motif and the receptors remain unknown. HPeVs can be detected in patient
      nasopharyngeal and stool samples, and infection is presumed to occur after
      respiratory or gastro-intestinal transmission. HPeV pathogenesis is poorly
      understood as there are no animal models and previous studies have been conducted
      in immortalized monolayer cell cultures which do not adequately represent the
      characteristics of human tissues. To bridge this gap, we determined the polarity
      of infection, replication kinetics, and cell tropism of HPeV1 and HPeV3 in the
      well-differentiated human airway epithelial (HAE) model. We found the HAE
      cultures to be permissive for HPeVs. Both HPeV genotypes infected the HAE
      preferentially from the basolateral surface while the progeny virus was shed
      toward the apical side. Confocal microscopy revealed the target cell type to be
      the p63+ basal cells for both viruses, alphaV ITG and HS blocking had no effect
      on the replication of either virus, and transcriptional profiling suggested that
      HPeV3 infection induced stronger immune activation than HPeV1. Genotype-specific
      host responses may contribute to the differences in pathogenesis and clinical
      outcomes associated with HPeV1 and HPeV3.

PMID- 30211128
TI  - Functional Characterization of Dense Granule Proteins in Toxoplasma gondii RH
      Strain Using CRISPR-Cas9 System.
AB  - Infection with the apicomplexan protozoan parasite Toxoplasma gondii is an
      ongoing public health problem. The parasite's ability to invade and replicate
      within the host cell is dependent on many effectors, such as dense granule
      proteins (GRAs) released from the specialized organelle dense granules, into host
      cells. GRAs have emerged as important determinants of T. gondii pathogenesis.
      However, the functions of some GRAs remain undefined. In this study, we used
      CRISPR-Cas9 technique to disrupt 17 GRA genes (GRA11, GRA12 bis, GRA13, GRA14,
      GRA20, GRA21, GRA28-31, GRA33-38, and GRA40) in the virulent T. gondii RH strain.
      The CRISPR-Cas9 constructs abolished the expression of the 17 GRA genes.
      Functional characterization of single DeltaGRA mutants was achieved in vitro
      using cell-based plaque assay and egress assay, and in vivo in BALB/c mice.
      Targeted deletion of these 17 GRA genes had no significant effect neither on the
      in vitro growth and egress of the mutant strains from the host cells nor on the
      parasite virulence in the mouse model of infection. Comparative analysis of the
      transcriptomics data of the 17 GRA genes suggest that GRAs may serve different
      functions in different genotypes and life cycle stages of the parasite. In sum,
      although these 17 GRAs might not be essential for RH strain growth in vitro or
      virulence in mice, they may have roles in other strains or parasite stages, which
      warrants further investigations.

PMID- 30211129
TI  - Blockade of Glutamate Receptors within the Prelimbic Cortex Attenuate
      Concentration of Excitatory Amino Acids in the Morphine Self-administration in
      Rats.
AB  - Background: The attitude of research on addiction has been done on the key role
      of glutamate. As a regard, the prelimbic cortex (PrL) has an important role in
      addiction, learning, and memory. We tried to investigate the level of glutamate
      and aspartate concentration after glutamate receptors blockade in this region in
      the morphine-addicted rats. Materials and Methods: In this study, we examined the
      effects of local infusion of the N-methyl-D-aspartate receptor and alpha-amino-3
      hydroxy-5-methylisoxazole-4-propionic acid receptor antagonists, 2-amino-5
      phosphonovaleric acid (AP5), and 6-cyano-7-nitroquinoxaline-2, 3-dione (CNQX),
      into the PrL cortex on the level of excitatory amino acids (EAAs) and glycine.
      After 11 days of self-administration, the prelimbic area of the brain was taken
      out, and the EAAs and glycine concentration was measured by high-performance
      liquid chromatography. Results: Morphine resulted in the significant increase in
      the EAAs concentration within this area (P <= 0.001). Microinjection of AP5 into
      this region before using of morphine significantly decreased the morphine-induced
      glutamate and aspartate concentration (P <= 0.001). CNQX had the same effect and
      significantly reduced the EAAs concentration compared to the morphine group (P <=
      0.001). In addition, microinjection of AP5 and CNQX simultaneously increased
      glycine concentration (P <= 0.001). Conclusions: These results show that morphine
      stimulates the EAAs release in the prelimbic area. It seems that microinjection
      of AP5 or CNQX in this region is effective in reducing morphine-induced EAA. It
      is suggested that EAA transmission in the PrL cortex may be a possible target for
      treatment of morphine addiction.

PMID- 30211130
TI  - Polyethylene Oxide and Silicon-Substituted Hydroxyapatite Composite: A
      Biomaterial for Hard Tissue Engineering in Orthopedic and Spine Surgery.
AB  - Background: Tissue engineering and biomaterials have made it possible to innovate
      bone treatments for orthopedic and spine problems. The aim of this study is to
      develop a novel polyethylene oxide (PEO)/silicon-substituted hydroxyapatite (Si
      HA) composite to be used as a scaffold for hard tissue engineering in orthopedic
      and spine procedures. Materials and Methods: The composite was fabricated through
      the electrospinning technique. The applied voltage (5 kV) and PEO concentration
      (5%) were fixed. Processing parameters such as the flow rates (20 MUl/min and 50
      MUl/min), distances from capillary tube to the collector (130 mm and 180 mm),
      spinning time (10 min and 20 min), and concentration of Si-HA (0.2% and 0.6%)
      were explored to find the optimum conditions to produce fine composite fibers.
      Results: Scanning electron microscope images showed that 5% PEO, 5% PEO/0.2% Si
      HA, and 5% PEO/0.6% Si-HA fibers were successively produced. Flow rates and
      working distances showed significant influence on the morphology of the polymeric
      and composite fibers. A high flow rate (50 MUl/min) and a larger working distance
      (180 mm) resulted in larger fibers. The comparison between the mean fiber
      diameter of 5% PEO/0.2% Si-HA and 5% PEO/0.6% Si-HA showed to be significantly
      different. As the Si-HA concentration increased, certain fibers were having
      particles of Si-HA that were not properly integrated into the polymer matrix.
      Conclusions: Synthesis of a novel biomaterial for hard tissue scaffold through
      electrospinning was successful. In general, PEO/Si-HA fibers produced have the
      desired characteristics to mimic the extracellular matrix of bone.

PMID- 30211132
TI  - Evaluation of Toxoplasma gondii B1 gene in Placental Tissues of Pregnant Women
      with Acute Toxoplasmosis.
AB  - Background: One of the consequences of toxoplasmosis is the risk of passing it
      from mother to fetus and the onset of congenital toxoplasmosis during pregnancy.
      The purpose of this study was to evaluate the B1 gene of Toxoplasma gondii in the
      placental tissues of pregnant women with acute toxoplasmosis. Materials and
      Methods: The study was a cross-sectional study. Serum samples of pregnant women
      who attended to Fatemieh Hospital of Hamadan University of Medical Sciences were
      tested for immunoglobulin G (IgG) antibodies against T. gondii by enzyme-linked
      immunosorbent assay. Then, polymerase chain reaction was used to identify the
      specific B1 gene of T. gondii in IgG seropositive women. The placental tissues of
      the pregnant women with positive serum B1 gene examined for this gene. Anti
      Toxoplasma immunoglobulin M (IgM) was performed on the umbilical cord and neonate
      blood. Results: Anti-Toxoplasma IgG was detected in 167 out of 653 (25.6%)
      pregnant women. T. gondii B1 gene was identified in 36 out of 167 (21.6%) of IgG
      seropositive women. After delivery, the B1 gene was evaluated in 15 out of 36
      (41.7%) patients' placental tissues, 13 of which were positive for this gene
      (86.7%). Anti-Toxoplasma IgM was detected neither in any umbilical cord nor in
      neonatal blood samples. All newborns, with the exception of one case, were born
      with normal birth weight and in term birth. Conclusion: The B1 gene was detected
      in 86.7% of the placental tissue of women who were involved in acute
      toxoplasmosis during pregnancy.

PMID- 30211131
TI  - Effects of Isolation and Social Subchronic Stresses on Food Intake and Levels of
      Leptin, Ghrelin, and Glucose in Male Rats.
AB  - Background: Exposure to psychological stresses can be a reason for obesity.
      Therefore, identifying the effective nutritional mechanisms such as feeding
      markers is of high necessity for the psychological stress conditions. Hence, the
      present study investigates the effects of subchronic isolation and social
      stresses on food intake, body weight differences (BWD), and levels of leptin,
      ghrelin, and glucose in rats. Materials and Methods: Eighteen male rats were
      randomly allocated into three groups: control (Co), isolation stress (IS), and
      social stress (SS) groups. Rats were under stresses for 7 days. The food intake
      (for three continuous hours after 16-18 h of food deprivation), BWD, levels of
      ghrelin, leptin, and glucose were measured. Results: The results showed that the
      food intake significantly (P < 0.05) reduced during the 1st h in the SS group
      compared to the Co group. At the 2nd h, the food intake significantly (P < 0.001
      and P < 0.01, respectively) decreased in the IS group compared to the Co and SS
      groups. The cumulative food intake and body weight were significantly (P < 0.05)
      reduced in the IS group compared to the Co group. The serum ghrelin level
      significantly reduced in the IS group compared to the Co group. Conclusions: The
      subchronic psychological stresses led to a reduction in food intake by the
      reduction of serum ghrelin levels. It seems that ghrelin might have a more
      fundamental role in the food intake with respect to the leptin and glucose levels
      in subchronic stress condition. Furthermore, the decreased body weight justified
      the reduction of food intake, particularly in subchronic isolation stress.

PMID- 30211133
TI  - Serum Zinc Level and Eating Behaviors in Children Receiving Zinc Supplements
      without Physician Prescription.
AB  - Background: The aim of the study was to compare the serum zinc level and eating
      behaviors in 2-8-year-old children with and without arbitrarily zinc
      supplementation. Materials and Methods: This case-control study was conducted
      from December 2015 to December 2017 in Isfahan, Iran. The case group consisted of
      seventy children, aged 2-8 years, who have received zinc supplement without
      physician prescription; the controls were an equal number of age-matched children
      who did not receive any supplement. The serum zinc level was measured, and eating
      behaviors were identified using Children's Eating Behavior Questionnaire (CEBQ).
      Results: There was no significant difference in serum zinc level between two
      groups (P = 0.18). Some differences in CEBQ subscales were identified between the
      groups studied. In the control group, the subscale of enjoyment of food was
      higher than the case group (P < 0.001). In the case group, the subscales of food
      fussiness and satiety responsiveness were higher than controls (P < 0.001).
      Conclusion: In this study, serum zinc levels were not significantly different
      between the two groups, and arbitrarily zinc supplementation does not play an
      important role in improving anorexia subscales.

PMID- 30211134
TI  - Effects of Nigella sativa Extracts on the Lipid Profile and Uncoupling Protein-1
      Gene Expression in Brown Adipose Tissue of Mice.
AB  - Background: Uncoupling protein-1 (UCP-1) is the index protein of the brown
      adipose tissue (BAT), used in the obesity studies. We evaluated the effects of
      thymoquinone (TQ), hydroalcoholic, and hexane extracts of Nigella sativa, on the
      UCP-1 gene expression in BAT, and also on the recovery from oxidative stress, due
      to a high-fat diet. Materials and Methods: Fifty mice were divided into five
      groups: the first group was fed with a usual diet and the second, third, fourth,
      and fifth groups with a high-fat diet, hydroalcoholic extract, hexane extract,
      and TQ, respectively. After completing the course, the lipid profile, paraoxonase
      1 (PON1), serum total antioxidant capacity (TAC), and malondialdehyde (MDA) were
      measured. UCP-1 expression in BAT was evaluated at the gene and protein level.
      Results: The weight of mice, receiving TQ, hydroalcoholic, and hexane extracts,
      was decreased (P < 0.05), compared to the second group (P < 0.05). MDA was
      increased in the second group, compared to the first group (P < 0.05); however,
      TAC, liver catalase enzyme, and PON1 were decreased (P < 0.05). Furthermore, MDA
      of the third, fourth, and fifth groups had decreased, and the activity of PON1,
      liver catalase enzyme, and the amount of TAC was increased (P < 0.05). UCP-1
      expression of the third and fourth groups was increased, compared to the second
      group (P < 0.05). Conclusion: The results suggest that TQ, hydroalcoholic, and
      hexane extracts of N. sativa have a protective and therapeutic role in the
      oxidative stress, caused by high-fat diets. The hydroalcoholic and hexane
      extracts can induce weight loss, by positively affecting UCP-1, at the gene and
      protein level.

PMID- 30211135
TI  - The Fusion Multistage Synthetic Peptides as the Best Candidates for New
      Tuberculosis Vaccine.

PMID- 30211137
TI  - Molecular Identification of Leishmania Parasites in Sand Flies (Diptera,
      Psychodidae) of an Endemic Foci in Poldokhtar, Iran.
AB  - Background: Cutaneous leishmaniasis is one of the most important public health
      problems in many developing countries. Sand flies, as vectors, transmit
      infectious forms of the parasite to the vertebrate hosts. Poldokhtar, South West
      of Iran, is one of the endemic foci of diseases with a little information about
      it. In this paper, we have tried to gather some useful information to control and
      to prevent this disease in this region. Materials and Methods: The present study
      was conducted to determine the vector(s), the parasite, and the species
      composition of sand flies in the Poldokhtar County during the months from July to
      September 2015. Sticky paper traps were used to collect sand flies from July to
      September. Species identification was done based on available diagnostic keys.
      Nested-polymerase chain reaction was performed to diagnosis the Leishmania
      infection of sand flies, and restriction fragment length polymorphism was used to
      identify the Leishmania species. Results: A total of 2000 specimens comprising 8
      species of sand flies (6 Phlebotomus and 2 Sergentomyia) were identified.
      Phlebotomus papatasi was the dominant species outdoor and Sergentomyia sintoni
      was the dominant species indoor. Among the 163 specimens of female P. papatasi,
      just 10 of them (6.1%) were positive to Leishmania major parasites. Conclusion:
      This is the first report of Leishmania infection of P. papatasi to L. major in
      this region. The results revealed that the high density of P. papatasi in outdoor
      and their infection with L. major is attributed that this species can play a
      major role as a principle vector in this region.

PMID- 30211136
TI  - Cognitive Functioning in Schizophrenia, Methamphetamine-induced Psychotic
      Disorder, and Healthy People: A Comparative Study.
AB  - Background: Methamphetamine-induced psychotic disorder (MIP) cannot be easily
      differentiated from other psychotic disorders. Some studies have reported that
      patients with MIP and schizophrenia have differences in their cognitive
      functioning. We hypothesized that their performance would be different on
      neuropsychological tests which assess executive functions and visual memory.
      Materials and Methods: In a cross-sectional study, 30 patients with MIP, 31
      patients with schizophrenia, and 31 healthy controls were assessed by Rey
      Osterrieth complex figure (ROCF) test and visual search and attention test
      (VSAT). One-way analysis of variance was performed to compare the mean scores of
      tests. Tukey's HSD test was used for post hoc analysis. Results: Three groups had
      significant differences according to ROCF test (F = 15.76, P < 0.0001), VSAT (F =
      39.78, P < 0.0001), left VSAT (F = 37.96, P < 0.0001), right VSAT (F = 40.40, P <
      0.0001), and the time of the test administration (F = 3.26, P = 0.04). The post
      hoc analysis showed that the mean score of ROCF test and VSAT (total, right, and
      left) was significantly higher in the control group than in the other two groups.
      The time of administering the test in the control group was significantly shorter
      than in the MIP group (P < 0.03) and nonsignificantly shorter than in the
      schizophrenia group (P = 0.54). The mean score of right side VSAT was
      significantly higher in the MIP group than in the schizophrenia group.
      Conclusion: ROCF could not differentiate MIP from schizophrenia. The better
      performance of patients with MIP on right side VSAT that is reported in this and
      in the previous study needs to be reevaluated in more controlled studies.

PMID- 30211138
TI  - Leucine-rich Repeat-containing G-protein Coupled Receptor 5 Gene Overexpression
      of the Rat Small Intestinal Progenitor Cells in Response to Orally Administered
      Grape Exosome-like Nanovesicles.
AB  - Background: Grape exosome-like nanovesicles (GELNs) have the advantage of
      inherent biocompatibility and biodegradability, the potential to be used as oral
      delivery vehicles. The objective of this research was to evaluate the efficiency
      of Syrah GELN purification and their effects on the intestinal stem cells when
      orally administrated to the rats. Materials and Methods: In this experimental
      study, Syrah GELN isolated by differential centrifugation and sucrose gradient
      ultracentrifugation method, then the concentration of protein, size, and zeta
      potential were measured as well as nanoparticles morphology. The stability of
      nanoparticles was investigated in the solution that mimicked the condition
      encountered in the stomach and intestine. To demonstrate transfection efficiency
      of intestinal stem cells, real-time PCR was carried out using rat leucine-rich
      repeat-containing G-protein-coupled receptor 5 (Lgr5)-specific primers on cDNA
      derived from total RNA extracted from the upper part of the small intestine of
      GELN-treated rats and their controls. Results: The mean size, zeta potential, and
      concentration of nanoparticles were 205.1 nm, -12.5 mV, and 250 MUg/ml,
      respectively. The result of stability test demonstrated that Syrah GELN were
      resistant to the harsh environment of the stomach. Lgr5 gene expression was
      increased by tenfold in GELN-treated rats compared with the controls.
      Conclusions: As intestinal stem cells are poorly accessible by common exogenous
      agents in vivo, oral delivery of GELNs provides a new approach to modulate the
      stem cell microenvironment for intestinal remodeling. This novel and effective
      method would help to overcome conditions such as inflammatory bowel disease,
      colorectal cancer, and applicable in regenerative medicine.

PMID- 30211139
TI  - Response to: Comment on "Establishing a Porcine Model of Small for Size Syndrome
      following Liver Resection".

PMID- 30211140
TI  - Ultrasound Grade of Liver Steatosis Is Independently Associated with the Risk of
      Metabolic Syndrome.
AB  - The aim of the study was to explore (a) prevalence and grade of nonalcoholic
      fatty liver (NAFL) among outpatients referred for abdominal ultrasound (US)
      examination and (b) relationship between the presence and severity of liver
      steatosis and metabolic syndrome (MS). This was a retrospective analysis of
      patients without history of liver disease examined by abdominal US in the
      University hospital setting. US was used to detect and semiquantitatively grade
      (0-3) liver steatosis. Data on patients' age, gender, body mass index (BMI),
      impaired glucose metabolism (IGM), atherogenic dyslipidaemia (AD), raised blood
      pressure (RBP), transaminases, and platelet counts were obtained from medical
      records. MS was defined as having at least 3 of the following components:
      obesity, IGM, AD, and RBP. Of the 631 patients (median age 60 years, median BMI
      27.4 kg/m2, and 57.4% females) 71.5% were overweight and 48.5% had NAFL. In the
      subgroup of 159 patients with available data on the components of MS, patients
      with higher US grade of steatosis had significantly higher BMI and increased
      prevalence of obesity, IGM, AD, RBP, and accordingly more frequently had MS,
      whereas they did not differ in terms of age and gender. NAFL was independently
      associated with the risk of having MS in a multivariate model adjusted for age,
      gender, BMI, and IGM. The grade of liver steatosis did not correlate with the
      presence of liver fibrosis. We demonstrated worrisome prevalence of obesity and
      NAFL in the outpatient population from our geographic region. NAFL is
      independently associated with the risk of having MS implying worse prognosis.

PMID- 30211142
TI  - Trainee Responses to Hurricane Harvey: Correlating Volunteerism With Burnout.
AB  - Background: Natural disasters take a heavy toll not only on their victims, but
      also on physicians who suffer vicarious trauma and burnout. New trainees in
      Houston, from entering PGY1 residents to entering fellows, underwent even more
      upheaval and stress during Hurricane Harvey. Many responded to calls for
      volunteer help. Objective: To investigate the impact of Hurricane Harvey on new
      trainees at our institution, and correlate volunteerism with measures of burnout
      and resilience. Methodology: Thirty three new trainees out of 90 (43% of
      population) from all specialties in our institution voluntarily responded to an
      online survey on the impact of Hurricane Harvey on their lives, whether or not
      they volunteered and in what form, and answered questions drawing from the
      abbreviated Maslach burnout survey and Resiliency Quiz. Statistical analyses were
      conducted using GraphPad Prism and Excel data analysis. Results: The top areas
      impacted were emotional health (32%), eating habits (29%), family (25%) and
      finances (25%). The main voluntary activities were covering for colleagues who
      could not make it to hospital (50%), donating money and supplies (36%), and
      cleaning and rebuilding (36%). Volunteering was associated with feelings of
      appreciation (76%), happiness (62%), thankfulness (57%), purposefulness (43%) and
      pride (33%). Fewer volunteers scored lowly in personal achievement as compared to
      non-volunteers (10 vs. 38%, p = 0.05). Significance: Hurricane Harvey affected
      health, finances and family of new trainees, more than half of whom volunteered
      to help. Volunteers had a greater sense of personal achievement as compared to
      non-volunteers. This may be due to having more volunteers among less burnt-out
      trainees or because volunteering reduced burnout and stress responses/trauma.
      These results suggest that volunteer opportunities should be made available in
      programs targeting resident burnout.

PMID- 30211141
TI  - Web-Based Motor Intervention to Increase Health-Related Physical Fitness in
      Children With Congenital Heart Disease: A Study Protocol.
AB  - Objective: Exercise interventions are underutilized in children with congenital
      heart disease (CHD) especially when the primary outcome is not peak oxygen
      uptake. Most of the studies are restricted to a low sample size and proximity of
      the patients to the study centers. Now eHealth approaches bear a promising but
      also challenging opportunity to transmit such intervention programs to
      participants, and check progress and compliance from remote. This study will aim
      to improve health-related physical fitness (HRPF) with a 24 weeks web-based
      exercise intervention. Methods and Design: The current study is planned as a
      randomized control trial (RCT) with a crossover design and the aim to improve
      functional outcome measures. It also estimates adherence and feasibility in
      patients with CHD in this web-based exercise/motor intervention over 24 weeks.
      Primary outcome will be the improvement of HRPF. Secondary outcomes are,
      functional and structural arterial stiffness measures and health-related quality
      of life. Thus, 70 children from 10 to 18 years with CHD of moderate and complex
      severity will be recruited and allocated randomly 1:1 in two study arms after
      baseline testing for their HRPF, arterial stiffness measures and health-related
      quality of life. For 24 weeks, participants in the intervention arm will receive
      three weekly exercise video clips of 20 min each. Every video clip comprises 20
      child-oriented exercises which have to be executed for 30 s followed by a
      recovery period of 30 s. Each session will start with 3-4 warming-up exercises,
      followed by 10-12 strength and flexibility exercises, and ending with 3-4 min of
      cool down or stretching tasks. Continuous video clips will be streamed from a web
      based e-Learning platform. The participant simply has to imitate the execution
      and follow some short advices. After each session, a brief online survey will be
      conducted to assess perceived exertion and feasibility. Discussion: The study
      will help to determine the efficacy and applicability of a web-based exercise
      intervention in children with CHD in regard to functional outcome measures. In
      addition, it will outline the effectiveness of remote monitoring, which provides
      a cost effective approach to reach patients with CHD that are low in prevalence
      and often do not live in close proximity to their tertiary center. Trial
      Registration: https://ClinicalTrials.gov Identifier: NCT03488797.

PMID- 30211143
TI  - Study Protocol: Determining Research Priorities of Young Albertan Families (The
      Family Research Agenda Initiative Setting Project-FRAISE)-Participatory Action
      Research.
AB  - Introduction: Pregnancy and childrearing can be an exciting and stressful time
      for new parents. The maternal-child health landscape has changed dramatically
      over the last few decades and research priorities need to address these rapid
      changes. There have been limited attempts to engage and collaborate with members
      of the public to develop research priorities for families who are expecting or
      parenting an infant to age 24 months. The work that has been completed has
      attempted to identify parental preference for information delivery and barriers
      to uptake of parenting programs but has not investigated parental research
      priorities. Methods: In collaboration with provincial research units and
      strategic clinical networks (SCN), we will use principles of participatory action
      research (PAR) as our theoretical framework/method, and a modified James Lind
      Alliance priority setting approach to prioritize a list of research questions
      that parents/knowledge users believe will support the health of their families.
      This will result in a top 10 list of parent/knowledge user-identified research
      priorities. This project will consist of three phases. In the first phase, we
      developed a steering committee of parents/knowledge users, healthcare providers,
      community agencies, and researchers to design a survey about health priorities
      for families. In the second phase, we will distribute the survey to diverse
      groups of parents/knowledge users/providers and hold a series of meetings to
      identify and prioritize potential questions from new parents about health issues
      from conception to age 24 months. In the third phase, we will collaboratively
      disseminate and translate findings. Discussion: This study will highlight
      parental health concerns and recommend parent-identified research priorities to
      inform future research projects needed to support the health of families between
      conception to age 24 months. Understanding the health research priorities of
      families in the community will help ensure future research contributes to
      meaningful changes in the health of young children, parents/knowledge users, and
      families. Ethics: This study and protocol have received ethical approved from the
      Conjoint Health Research Ethics Board at the University of Calgary (REB17-0014).
      Dissemination: The top 10 research priorities will be published and additional
      findings from the study will be distributed through pamphlets and newsletters.

PMID- 30211145
TI  - Editorial: Structural Transitions in the Health Care Systems in Times of
      Uncertainty.

PMID- 30211144
TI  - Lassa Fever 2016 Outbreak in Plateau State, Nigeria-The Changing Epidemiology and
      Clinical Presentation.
AB  - Lassa fever (LF) outbreaks in Nigeria mostly occur in rural areas and during the
      dry season, peaking between December through February. Fever is a cardinal
      presenting feature among the myriad manifestations of LF. Thirty four patients
      with clinical diagnosis of LF were analyzed. However, only 11 (32%) LASV
      infections were confirmed by RT-PCR. The 2016 LF outbreak showed a preferential
      urban occurrence and a high case fatality. Fever (>=38 degrees C) was not
      detected in over a fourth of the patients at the time of examination. Bleeding
      diathesis was the most common presentation while abdominal pain and headache were
      present in more than half of the confirmed cases. Changes in the geographical
      distribution and clinical presentation may have implications for disease control
      efforts and the risk of transmission, both locally and internationally. In order
      to guide interventions, public health authorities should be aware that the
      epidemic patterns may be changing.

PMID- 30211146
TI  - An Upgraded Smartphone-Based Program for Leisure and Communication of People With
      Intellectual and Other Disabilities.
AB  - Background: People with intellectual disability and sensory or sensory-motor
      impairments may display serious problems in managing functional daily activities
      as well as leisure activities and communication with distant partners. Aim: The
      study assessed an upgraded smartphone-based program to foster independent leisure
      and communication activity of eight participants with mild to moderate
      intellectual disability, sensory or sensory-motor impairments, and limited speech
      skills. Method: The upgraded program was based on the use of (a) a Samsung Galaxy
      A3 smartphone with Android 6.0 Operating System, near-field communication, music
      and video player functions, and Macrodroid application, and (b) special radio
      frequency-code labels. Participants requested leisure and communication
      activities by placing mini objects or pictures representing those activities and
      containing frequency-code labels on the smartphone. The smartphone, via the
      Macrodroid application, read the labels (i.e., discriminated the participants'
      requests) and provided the participants with the activities requested. Results:
      During the baseline (i.e., in the absence of the program), the participants
      failed to request/access leisure and communication activities independently.
      During the post-intervention phase of the study (i.e., using the program), they
      succeeded in requesting/accessing those activities independently and spent about
      70-90% of their session time busy with those activities. Conclusion: The upgraded
      smartphone-based program may be highly functional for people like the
      participants of this study.

PMID- 30211147
TI  - Integrating Kindergartener-Specific Questionnaires With Citizen Science to
      Improve Child Health.

PMID- 30211149
TI  - NHC in Imidazolium Acetate Ionic Liquids: Actual or Potential Presence?
AB  - Ionic liquids (ILs) are considered in the majority of cases green solvents, due
      to their virtually null vapor pressure and to the easiness in recycling them. In
      particular, imidazolium ILs are widely used in many fields of Chemistry, as
      solvents or precursors of N-heterocyclic carbenes (NHCs). The latter are easily
      obtained by deprotonation of the C2-H, usually using strong bases or cathodic
      reduction. Nevertheless, it is known that weaker bases (e.g., triethylamine) are
      able to promote C2-H/D exchange. From this perspective, the possibility of
      deprotonating C2-H group of an imidazolium cation by means of a basic counter-ion
      was seriously considered and led to the synthesis of imidazolium ILs
      spontaneously containing NHCs. The most famous of this class of ILs are N,N'
      disubstituted imidazolium acetates. Due to the particular reactivity of this kind
      of ILs, they were appointed as "organocatalytic ionic liquids" or "proto
      carbenes." Many papers report the use of these imidazolium acetates in
      organocatalytic reactions (i. e., catalyzed by NHC) or in stoichiometric NHC
      reactions (e.g., with elemental sulfur to yield the corresponding imidazole-2
      thiones). Nevertheless, the actual presence of NHC in N,N'-disubstituted
      imidazolium acetate is still controversial. Moreover, theoretical studies seem to
      rule out the presence of NHC in such a polar environment as an IL. Aim of this
      Mini Review is to give the reader an up-to-date overview on the actual or
      potential presence of NHC in such an "organocatalytic ionic liquid," both from
      the experimental and theoretical point of view, without the intent to be
      exhaustive on N,N'-disubstituted imidazolium acetate applications.

PMID- 30211148
TI  - New Properties of a Bioinspired Pyridine Benzimidazole Compound as a Novel
      Differential Staining Agent for Endoplasmic Reticulum and Golgi Apparatus in
      Fluorescence Live Cell Imaging.
AB  - In this study, we explored new properties of the bioinspired pyridine
      benzimidazole compound B2 (2,4-di-tert-butyl-6-(3H-imidazo[4,5-c]pyridine-2
      yl)phenol) regarding its potential use as a differential biomarker. For that, we
      performed 1D 1HNMR (TOCSY), UV-Vis absorption spectra in different organic
      solvents, voltammetry profile (including a scan-rate study), and TD-DFT
      calculations that including NBO analyses, to provide valuable information about
      B2 structure and luminescence. In our study, we found that the B2 structure is
      highly stable, where the presence of an intramolecular hydrogen bond (IHB) seems
      to have a crucial role in the stability of luminescence, and its emission can be
      assigned as fluorescence. In fact, we found that the relatively large Stokes
      Shift observed for B2 (around 175 nm) may be attributed to the stability of the
      B2 geometry and the strength of its IHB. On the other hand, we determined that B2
      is biocompatible by cytotoxicity experiments in HeLa cells, an epithelial cell
      line. Furthermore, in cellular assays we found that B2 could be internalized by
      passive diffusion in absence of artificial permeabilization at short incubation
      times (15 min to 30 min). Fluorescence microscopy studies confirmed that B2
      accumulates in the endoplasmic reticulum (ER) and Golgi apparatus, two organelles
      involved in the secretory pathway. Finally, we determined that B2 exhibited no
      noticeable blinking or bleaching after 1 h of continuous exposure. Thus, B2
      provides a biocompatible, rapid, simple, and efficient way to fluorescently label
      particular organelles, producing similar results to that obtained with other well
      established but more complex methods.

PMID- 30211150
TI  - Anisotropic Polymer Adsorption on Molybdenite Basal and Edge Surfaces and
      Interaction Mechanism With Air Bubbles.
AB  - The anisotropic surface characteristics and interaction mechanisms of molybdenite
      (MoS2) basal and edge planes have attracted much research interest in many
      interfacial processes such as froth flotation. In this work, the adsorption of a
      polymer depressant [i.e., carboxymethyl cellulose (CMC)] on both MoS2 basal and
      edge surfaces as well as their interaction mechanisms with air bubbles have been
      characterized by atomic force microscope (AFM) imaging and quantitative force
      measurements. AFM imaging showed that the polymer coverage on the basal plane
      increased with elevating polymer concentration, with the formation of a compact
      polymer layer at 100 ppm CMC; however, the polymer adsorption was much weaker on
      the edge plane. The anisotropy in polymer adsorption on MoS2 basal and edge
      surfaces coincided with water contact angle results. Direct force measurements
      using CMC functionalized AFM tips revealed that the adhesion on the basal plane
      was about an order of magnitude higher than that on the edge plane, supporting
      the anisotropic CMC adsorption behaviors. Such adhesion difference could be
      attributed to their difference in surface hydrophobicity and surface charge, with
      weakened hydrophobic attraction and strengthened electrostatic repulsion between
      the polymers and edge plane. Force measurements using a bubble probe AFM showed
      that air bubble could attach to the basal plane during approach, which could be
      effectively inhibited after polymer adsorption. The edge surface, due to the
      negligible polymer adsorption, showed similar interaction behaviors with air
      bubbles before and after polymer treatment. This work provides useful information
      on the adsorption of polymers on MoS2 basal/edge surfaces as well as their
      interaction mechanism with air bubbles at the nanoscale, with implications for
      the design and development of effective polymer additives to mediate the bubble
      attachment on solid particles with anisotropic surface properties in mineral
      flotation and other engineering processes.

PMID- 30211152
TI  - Recent Advances of SnO2-Based Sensors for Detecting Fault Characteristic Gases
      Extracted From Power Transformer Oil.
AB  - Tin oxide SnO2-based gas sensors have been widely used for detecting typical
      fault characteristic gases extracted from power transformer oil, namely, H2, CO,
      CO2, CH4, C2H2, C2H4, and C2H6, due to the remarkable advantages of high
      sensitivity, fast response, long-term stability, and so on. Herein, we present an
      overview of the recent significant improvement in fabrication and application of
      high performance SnO2-based sensors for detecting these fault characteristic
      gases. Promising materials for the sensitive and selective detection of each kind
      of fault characteristic gas have been identified. Meanwhile, the corresponding
      sensing mechanisms of SnO2-based gas sensors of these fault characteristic gases
      are comprehensively discussed. In the final section of this review, the major
      challenges and promising developments in this domain are also given.

PMID- 30211151
TI  - Essentials of Aquaphotomics and Its Chemometrics Approaches.
AB  - Aquaphotomics is a novel scientific discipline involving the study of water and
      aqueous systems. Using light-water interaction, it aims to extract information
      about the structure of water, composed of many different water molecular
      conformations using their absorbance bands. In aquaphotomics analysis, specific
      water structures (presented as water absorbance patterns) are related to their
      resulting functions in the aqueous systems studied, thereby building an
      aquaphotome-a database of water absorbance bands and patterns correlating
      specific water structures to their specific functions. Light-water interaction
      spectroscopic methods produce complex multidimensional spectral data, which
      require data processing and analysis to extract hidden information about the
      structure of water presented by its absorbance bands. The process of extracting
      information from water spectra in aquaphotomics requires a field-specific
      approach. It starts with an appropriate experimental design and execution to
      ensure high-quality spectral signals, followed by a multitude of spectral
      analysis, preprocessing and chemometrics methods to remove unwanted influences
      and extract water absorbance spectral pattern related to the perturbation of
      interest through the identification of activated water absorbance bands found
      among the common, consistently repeating and highly influential variables in all
      analytical models. The objective of this paper is to introduce the field of
      aquaphotomics and describe aquaphotomics multivariate analysis methodology
      developed during the last decade. Through a worked-out example of analysis of
      potassium chloride solutions supported by similar approaches from the existing
      aquaphotomics literature, the provided instruction should give enough information
      about aquaphotomics analysis i.e. to design and perform the experiment and data
      analysis as well as to represent water absorbance spectral pattern using various
      forms of aquagrams-specifically designed aquaphotomics graphs. The explained
      methodology is derived from analysis of near infrared spectral data of aqueous
      systems and will offer a useful and new tool for extracting data from
      informationally rich water spectra in any region. It is the hope of the authors
      that with this new tool at the disposal of scientists and chemometricians,
      pharmaceutical and biomedical spectroscopy will substantially progress beyond its
      state-of-the-art applications.

PMID- 30211154
TI  - Contribution of Blood Orange-Based Beverages to Bioactive Compounds Intake.
AB  - The study aimed at screening the levels of ascorbic acid, hydroxycinnamic acids
      (HCAs) and total anthocyanins in commercial beverages containing blood orange
      juice (BOJ), estimating the contribution of these products to the intake of
      health-promoting compounds and at discussing the actual value of the products on
      a price/bioactive level basis. Results demonstrate that the reference to BOJ in
      many beverages is misleading, as inferred from the very low bioactive levels
      observed. These beverages, in label should refer as "water-based" instead of
      "fruit-based beverage." Accordingly, the intake of bioactives from BOJ-based
      beverages, with the exception of ascorbic acid used in the most cases as
      preservative, is often very low. The intake of bioactive components from blood
      orange consumption is much higher compared to the consumption of BOJ-based
      beverages, hence the consumption of blood oranges and 100% BOJs should be
      preferred in order to guarantee the intake of a rich pool of bioactive compounds.
      Finally, the market value of BOJ-based beverages is not correlated with their
      real nutritional value: the relative unitary cost of the three classes of
      bioactive compounds considered increased in the order: fresh blood oranges < 100%
      BOJ < BOJ-based beverages. Hence, the consumption of fresh blood oranges
      represents the cheapest way to ensure the intake of health-promoting bioactive
      compounds such as anthocyanins and HCAs.

PMID- 30211153
TI  - Selectivity and Reactivity of ZrIV and CeIV Substituted Keggin Type
      Polyoxometalates Toward Cytochrome c in Surfactant Solutions.
AB  - In this paper we investigate the effect of three different types of surfactants,
      on the hydrolysis of Cytochrome c (Cyt c), a predominantly alpha helical protein
      containing a heme group, promoted by [Ce(alpha PW11O39)2]10- (CeK) and [Zr(alpha
      PW11O39)2]10- (ZrK) polyoxometalates. In the presence of SDS, Zw3 12, or CHAPS
      surfactants, which are commonly used for solubilizing hydrophobic proteins, the
      specificity of CeK or ZrK toward hydrolysis of Cyt c does not change. However,
      the hydrolysis rate of Cyt c by CeK was increased in the presence of SDS, but
      decreased in the presence of CHAPS, and was nearly inhibited in the presence of
      Zw3 12. The Circular dichroism and Tryptophan fluorescence spectroscopy have
      shown that the structural changes in Cyt c caused by surfactants are similar to
      those caused by POMs, hence the same specificity in the absence or presence of
      surfactants was observed. The results also indicate that for Cyt c hydrolysis to
      occur, large unfolding of the protein is needed in order to accommodate the POMs.
      While SDS readily unfolds Cyt c, the protein remains largely folded in the
      presence of CHAPS and Zw3 12. Addition of POMs to Cyt c solutions in CHAPS
      results in unfolding of the structure allowing the interaction with POMs to occur
      and results in protein hydrolysis. Zw3 12, however, locks Cyt c in a conformation
      that resists unfolding upon addition of POM, and therefore results in nearly
      complete inhibition of protein hydrolysis.

PMID- 30211155
TI  - Strategic Isolation of a Polyoxocation Mimicking Vanadium(V) Oxide Layered
      Structure by Stacking of [H2V2O8]4- Anions Bridged by (1,4,7
      Triazacyclononane)Co(III) Complexes.
AB  - An isolation of a vanadium(V) oxide cluster mimicking V2O5 layered structure was
      achieved formulated as [{Co(tacn)}4V4O12(OH)4]4+ (1) (tacn = 1,4,7
      triazacyclononane). From the 51V NMR spectra of the reaction mixtures, we
      optimized the reaction condition in terms of a molar ratio of VO43- and
      [Co(tacn)(H2O)3]3+ as well as a pH value. Cluster 1 is stable in a wide range of
      pH values from 1.5 to 8.0, and the presence of multiple hydrogen bondings in the
      structure is a unique feature. In the X-ray analysis of cluster 1, the V? V
      distances are classified into two groups of relatively shorter distances
      (2.978(1) A) and longer interactions (3.554(1) A), and it is a good model of the
      substructure of V2O5 bulk material. As far as we know, this is a first example of
      an isolation of mixed-metal cluster including a unit of V2O5 structure by a stack
      of two layers of [H2V2O8]4-, although cubic V4O4 cubane-type clusters are well
      known. The solid sample of compound 1-Cl and 1-Br shows reversible thermochromic
      behavior accompanied by crystal to amorphous transformation upon hydration
      dehydration process.

PMID- 30211156
TI  - A Five-Component Biginelli-Diels-Alder Cascade Reaction.
AB  - A new multi-component condensation was discovered during the reaction of a urea,
      beta-keto ester, and formaldehyde. In the presence of catalytic indium bromide, a
      Biginelli dihydropyrimidinone intermediate was further converted to a five
      component condensation product through a formal hetero Diels-Alder reaction. The
      product structure was confirmed by NMR and NOE analysis, and the proposed
      stepwise mechanism was supported by the reaction of the Biginelli intermediate
      with ethyl 2-methylene-3-oxobutanoate.

PMID- 30211157
TI  - Size-Tunable Natural Mineral-Molybdenite for Lithium-Ion Batteries Toward:
      Enhanced Storage Capacity and Quicken Ions Transferring.
AB  - Restricted by the dissatisfied capacity of traditional materials, lithium-ion
      batteries (LIBs) still suffer from the low energy-density. The pursuing of
      natural electrode resources with high lithium-storage capability has triggered a
      plenty of activities. Through the hydro-refining process of raw molybdenite ore,
      containing crushing-grinding, flotation, exfoliation, and gradient
      centrifugation, 2D molybdenum disulfide (MoS2) with high purity is massively
      obtained. The effective tailoring process further induce various sizes (5, 2, 1
      and 90 nm) of sheets, accompanying with the increasing of active sites and
      defects. Utilized as LIB anodes, size-tuning could serve crucial roles on the
      electrochemical properties. Among them, MoS2-1 MUm delivers an initial charge
      capacity of 904 mAh g-1, reaching up to 1,337 mAh g-1 over 125 loops at 0.1 A g
      1. Even at 5.0 A g-1, a considerable capacity of 682 mAh g-1 is remained.
      Detailedly analyzing kinetic origins reveals that size-controlling would bring
      about lowered charge transfer resistance and quicken ions diffusion. The work is
      anticipated to shed light on the effect of different MoS2 sheet sizes on Li
      capacity ability and provides a promising strategy for the commercial-scale
      production of natural mineral as high-capacity anodes.

PMID- 30211158
TI  - Photocatalytic Activity of Polymer Nanoparticles Modulates Intracellular Calcium
      Dynamics and Reactive Oxygen Species in HEK-293 Cells.
AB  - Optical modulation of living cells activity by light-absorbing exogenous
      materials is gaining increasing interest, due to the possibility both to achieve
      high spatial and temporal resolution with a minimally invasive and reversible
      technique and to avoid the need of viral transfection with light-sensitive
      proteins. In this context, conjugated polymers represent ideal candidates for
      photo-transduction, due to their excellent optoelectronic and biocompatibility
      properties. In this work, we demonstrate that organic polymer nanoparticles,
      based on poly(3-hexylthiophene) conjugated polymer, establish a functional
      interaction with an in vitro cell model (Human Embryonic Kidney cells, HEK-293).
      They display photocatalytic activity in aqueous environment and, once
      internalized within the cell cytosol, efficiently generate reactive oxygen
      species (ROS) upon visible light excitation, without affecting cell viability.
      Interestingly, light-activated ROS generation deterministically triggers
      modulation of intracellular calcium ion flux, successfully controlled at the
      single cell level. In perspective, the capability of polymer NPs to produce ROS
      and to modulate Ca2+ dynamics by illumination on-demand, at non-toxic levels, may
      open the path to the study of biological processes with a gene-less approach and
      unprecedented spatio-temporal resolution, as well as to the development of new
      biotechnology tools for cell optical modulation.

PMID- 30211159
TI  - Extracellular Vesicles: Decoding a New Language for Cellular Communication in
      Early Embryonic Development.
AB  - The blastocyst inner cell mass (ICM) that gives rise to a whole embryo in vivo
      can be derived and cultured in vitro as embryonic stem cells (ESCs), which retain
      full developmental potential. ICM cells receive, from diverse sources, complex
      molecular and spatiotemporal signals that orchestrate the finely-tuned processes
      associated with embryogenesis. Those instructions come, continuously, from
      themselves and from surrounding cells, such as those present in the trophectoderm
      and primitive endoderm (PrE). A key component of the ICM niche are the
      extracellular vesicles (EVs), produced by distinct cell types, that carry and
      transfer key molecules that regulate target cells and modulate cell renewal or
      cell fate. A growing number of studies have demonstrated the extracellular
      circulation of morphogens, a group of classical regulators of embryo development,
      are carried by EVs. miRNAs are also an important cargo of the EVs that have been
      implicated in tissue morphogenesis and have gained special attention due to their
      ability to regulate protein expression through post-transcriptional modulation,
      thereby influencing cell phenotype. This review explores the emerging evidence
      supporting the role of EVs as an additional mode of intercellular communication
      in early embryonic and ESCs differentiation.

PMID- 30211162
TI  - Editorial: Molecular Mechanisms of Metalloid Transport, Toxicity and Tolerance.

PMID- 30211161
TI  - A Paradoxical Correlation of Cancer-Associated Fibroblasts With Survival Outcomes
      in B-Cell Lymphomas and Carcinomas.
AB  - The tumor microenvironment is increasingly recognized as an active participant in
      tumor progression. A recent pan-cancer genomic profile analysis has revealed that
      gene signatures representing components of the tumor microenvironment are robust
      predictors of survival. A stromal gene signature representing fibroblasts and
      extracellular matrix components has been associated with good survival in diffuse
      large B-cell lymphoma (DLBCL). Paradoxically, a closely related gene signature
      has been shown to correlate with poor survival in carcinomas, including breast,
      ovarian, pancreatic, and colorectal cancer. To date, there has been no
      explanation for this paradoxical inverse correlation with survival outcomes in
      DLBCL and carcinomas. Using public gene data sets, we confirm that the DLBCL
      stromal gene signature is associated with good survival in DLBCL and several
      other B-cell lymphomas while it is associated with poor survival in ovarian
      cancer and several other solid tumors. We show that the DLBCL stromal gene
      signature is enriched in lymphoid fibroblasts in normal lymph nodes and in cancer
      associated fibroblasts (CAFs) in ovarian cancer. Based on these findings, we
      propose several possible mechanisms by which CAFs may contribute to opposite
      survival outcomes in B-cell lymphomas and carcinomas.

PMID- 30211163
TI  - Melanoma LAMP-2C Modulates Tumor Growth and Autophagy.
AB  - Autophagy plays critical but diverse roles in cellular quality control and
      homeostasis potentially checking tumor development by removing mutated or damaged
      macromolecules, while conversely fostering tumor survival by supplying essential
      nutrients during cancer progression. This report documents a novel inhibitory
      role for a lysosome-associated membrane protein, LAMP-2C in modulating autophagy
      and melanoma cell growth in vitro and in vivo. Solid tumors such as melanomas
      encounter a variety of stresses in vivo including inflammatory cytokines produced
      by infiltrating lymphocytes directed at limiting tumor growth and spread. Here,
      we report that in response to the anti-tumor, pro-inflammatory cytokine
      interferon-gamma, melanoma cell expression of LAMP2C mRNA significantly
      increased. These results prompted an investigation of whether increased melanoma
      cell expression of LAMP-2C might represent a mechanism to control or limit human
      melanoma growth and survival. In this study, enhanced expression of human LAMP-2C
      in melanoma cells perturbed macroautophagy and chaperone-mediated autophagy in
      several human melanoma lines. In vitro analysis showed increasing LAMP-2C
      expression in a melanoma cell line, triggered reduced cellular LAMP-2A and LAMP
      2B protein expression. Melanoma cells with enhanced LAMP-2C expression displayed
      increased cell cycle arrest, increased expression of the cell cycle regulators
      Chk1 and p21, and greater apoptosis and necrosis in several cell lines tested.
      The increased abundance of Chk1 protein in melanoma cells with increased LAMP-2C
      expression was not due to higher CHEK1 mRNA levels, but rather an increase in
      Chk1 protein abundance including Chk1 molecules phosphorylated at Ser345. Human
      melanoma cell xenografts with increased LAMP-2C expression, displayed reduced
      growth in immune compromised murine hosts. Melanomas with high LAMP-2C expression
      showed increased necrosis and reduced cell density upon histological analysis.
      These results reveal a novel role for LAMP-2C in negatively regulating melanoma
      growth and survival.

PMID- 30211165
TI  - Ultraviolet A1 Phototherapy for Fibrosing Conditions.
AB  - In this article we describe efficacy and safety aspects of ultraviolet A1 (UV-A1)
      phototherapy in fibrosing conditions. UV-A1 is a specific phototherapeutic
      modality that is defined by a selective spectral range (340-400 nm). UV-A1
      includes distinct modes of action qualifying this method for therapy of a variety
      of conditions, in particular fibrosing skin diseases. Concerning efficacy of UV
      A1 phototherapy in fibrosing conditions, the best evidence obtained from
      randomized controlled trials exists for localized scleroderma. Moreover,
      fibrosing disorders such as lichen sclerosus and graft-vs.-host disease can be
      treated successfully by means of UV- A1. Regarding the optimal dosage regimen
      medium-dose UV-A1 seems to be linked to the best benefit/risk ratio. Possible
      acute adverse events of UV-A1 phototherapy include erythema and provocation of
      photodermatoses. Skin ageing and skin cancer formation belong to the chronic
      adverse events that may occur after long-term UV-A1 phototherapy.

PMID- 30211164
TI  - Extracorporeal Photopheresis-An Overview.
AB  - Extracorporeal photopheresis (ECP) has been in clinical use for over three
      decades after receiving FDA approval for the palliative treatment of the Sezary
      Syndrome variant of cutaneous T-cell lymphoma (CTCL) in 1988. After the first
      positive experiences with CTCL, additional indications have been successfully
      explored including areas such as graft-vs.-host disease (GVHD), scleroderma, and
      solid organ transplantation. The mechanism of action is still not fully resolved,
      but important steps in understanding ECP in recent years have been very
      informative. Originally, the primary hypothesis stated that psoralen and
      ultraviolet A (UVA) in combination induce apoptosis in the treated immune cells.
      This view shifted in favor of dendritic cell initiation, modification of the
      cytokine profile and stimulation of several T-cell lineages, in particular
      regulatory T-cells. A number of ECP guidelines have been produced to optimize
      treatment regimens in the clinical context. In CTCL, enough evidence is available
      for the use of ECP as a first line treatment for Sezary Syndrome (SS), but also
      as a second line or rescue treatment in therapy-refractory forms of mycosis
      fungoides (MF). ECP in the treatment of acute and chronic GVHD has shown
      promising results as second line therapy in steroid-refractory presentations. In
      solid organ transplantation, ECP has been used to increase tissue tolerance and
      decrease infections with opportunistic pathogens, attributed to the use of high
      doses of immunosuppressive medication. Infection with cytomegalovirus (CMV)
      remains a limiting factor affecting survival in solid organ transplantation and
      the role of ECP will be discussed in this review. A trend toward prophylactic use
      of ECP can be observed and may further contribute to improve the outcome in many
      patients. To further deepen our knowledge of ECP and thus facilitate its use in
      patients that potentially benefit most from it, future prospective randomized
      trials are urgently needed in this rapidly growing field. The aim of this review
      is to (1) introduce the method, (2) give an overview where ECP has shown
      promising effects and has become an essential part of treatment protocols, and
      (3) to give recommendations on how to proceed in numerous indications.

PMID- 30211166
TI  - On the Way to in vitro Platelet Production.
AB  - The severely decreased platelet counts (10-30. 103 platelets/MUL) frequently
      observed in patients undergoing chemotherapy, radiation treatment, or organ
      transplantation are associated with life-threatening increased bleeding risks. To
      circumvent these risks, platelet transfusion remains the treatment of choice,
      despite some limitations which include a limited shelf-life, storage-related
      deterioration, the development of alloantibodies in recipients and the
      transmission of infectious diseases. A sustained demand has evolved in recent
      years for controlled blood products, free of infectious, inflammatory, and immune
      risks. As a consequence, the challenge for blood centers in the near future will
      be to ensure an adequate supply of blood platelets, which calls for a
      reassessment of our transfusion models. To meet this challenge, many laboratories
      are now turning their research efforts toward the in vitro and customized
      production of blood platelets. In recent years, there has been a major enthusiasm
      for the cultured platelet production, as illustrated by the number of reviews
      that have appeared in recent years. The focus of the present review is to
      critically asses the arguments put forward in support of the culture of platelets
      for transfusion purposes. In light of this, we will recapitulate the main
      advances in this quickly evolving field, while noting the technical limitations
      to overcome to make cultured platelet a transfusional alternative.

PMID- 30211168
TI  - Cystic Fibrosis Kidney Disease: 10 Tips for Clinicians.
AB  - Increased longevity in people with cystic fibrosis (CF) means that more people
      are surviving long enough to develop kidney complications. Nephrologists and
      their colleagues now face a steep learning curve as many of them encounter
      patients with CF related kidney disease (CFKD) for the first time. This article
      presents perspectives from a medical sociologist with CF on what renal health
      professionals should know about people with CFKD. It outlines challenges that
      people with CFKD as they age, framing these struggles as opportunities for
      clinicians to help these unique patients achieve and maintain their best possible
      quality of life.

PMID- 30211167
TI  - Fertility Sparing Treatment in Patients With Early Stage Endometrial Cancer,
      Using a Combination of Surgery and GnRH Agonist: A Monocentric Retrospective
      Study and Review of the Literature.
AB  - : Objectives: To evaluate the efficacy and safety of gonadotropin-releasing
      hormone (GnRH) agonist after endometrial resection in women suffering early stage
      endometrial carcinoma (EC) and/or endometrial intra-epithelial neoplasia (EIN).
      Design: A retrospective review of clinical files between January 1999 and
      December 2016. Setting: University hospital. Patients: Eighteen women younger
      than 41 years with grade 1 endometrial carcinoma (G1EC) and/or Endometrial intra
      epithelial neoplasia (EIN). INTERVENTIONS: All patients received GnRH agonist for
      3 months after an endometrial resection combined with a laparoscopy to exclude
      concomitant ovarian tumor and/or other extra-uterine disease. The patient
      underwent a follow-up of 3 months interval with endometrial sampling by
      hysteroscopy. Main Outcome Measure(s): The recurrence rate and the pregnancy rate
      after fertility sparing treatment. Results: We identified 9 patients with EIN
      (50%), 7 patients with G1EC (38.9%), 1 with combined histology (5.5%), and 1 with
      G2EC (5.5%). After a median follow-up of 40.7 months, 12 patients conserved their
      uterus (66.7%), and 8 (53.3%) patients were pregnant with a total of 14
      pregnancies among those who tried to become pregnant. We observed a complete
      response rate in 12 patients (66.7%) but 3 of these patients relapsed (25%). We
      also found a stable disease in 6 patients (33.3%). Conclusions: Compared with
      other fertility sparing treatments, GnRH agonist after surgery is an effective
      fertility-sparing strategy for women with EIN and/or G1EC. We recommend
      hysterectomy once a family has been completed even if the literature does not
      clearly lead to radical surgery.

PMID- 30211170
TI  - Engagement Rules That Underpin DBL-DARC Interactions for Ingress of Plasmodium
      knowlesi and Plasmodium vivax Into Human Erythrocytes.
AB  - Malaria parasite erythrocytic stages comprise of repeated bursts of parasites via
      cyclical invasion of host erythrocytes using dedicated receptor-ligand
      interactions. A family of erythrocyte-binding proteins from Plasmodium knowlesi
      (Pk) and Plasmodium vivax (Pv) attach to human Duffy antigen receptor for
      chemokines (DARC) via their Duffy binding-like domains (DBLs) for invasion. Here
      we provide a novel, testable and overarching interaction model that rationalizes
      even contradictory pieces of evidence that have so far existed in the literature
      on Pk/Pv-DBL/DARC binding determinants. We further address the conundrum of how
      parasite-encoded Pk/Pv-DBLs recognize human DARC and collate evidence for two
      distinct DARC integration sites on Pk/Pv-DBLs.

PMID- 30211160
TI  - CD44/CD44v6 a Reliable Companion in Cancer-Initiating Cell Maintenance and Tumor
      Progression.
AB  - Metastasis is the leading cause of cancer death, tumor progression proceeding
      through emigration from the primary tumor, gaining access to the circulation,
      leaving the circulation, settling in distant organs and growing in the foreign
      environment. The capacity of a tumor to metastasize relies on a small
      subpopulation of cells in the primary tumor, so called cancer-initiating cells
      (CIC). CIC are characterized by sets of markers, mostly membrane anchored
      adhesion molecules, CD44v6 being the most frequently recovered marker. Knockdown
      and knockout models accompanied by loss of tumor progression despite unaltered
      primary tumor growth unraveled that these markers are indispensable for CIC. The
      unexpected contribution of marker molecules to CIC-related activities prompted
      research on underlying molecular mechanisms. This review outlines the
      contribution of CD44, particularly CD44v6 to CIC activities. A first focus is
      given to the impact of CD44/CD44v6 to inherent CIC features, including the
      crosstalk with the niche, apoptosis-resistance, and epithelial mesenchymal
      transition. Following the steps of the metastatic cascade, we report on
      supporting activities of CD44/CD44v6 in migration and invasion. These CD44/CD44v6
      activities rely on the association with membrane-integrated and cytosolic
      signaling molecules and proteases and transcriptional regulation. They are not
      restricted to, but most pronounced in CIC and are tightly regulated by feedback
      loops. Finally, we discuss on the engagement of CD44/CD44v6 in exosome
      biogenesis, loading and delivery. exosomes being the main acteurs in the long
      distance crosstalk of CIC with the host. In brief, by supporting the
      communication with the niche and promoting apoptosis resistance CD44/CD44v6 plays
      an important role in CIC maintenance. The multifaceted interplay between
      CD44/CD44v6, signal transducing molecules and proteases facilitates the
      metastasizing tumor cell journey through the body. By its engagement in exosome
      biogenesis CD44/CD44v6 contributes to disseminated tumor cell settlement and
      growth in distant organs. Thus, CD44/CD44v6 likely is the most central CIC
      biomarker.

PMID- 30211171
TI  - Supplemental Oxygen Protects Heart Against Acute Myocardial Infarction.
AB  - Myocardial infarction (MI), which occurs often due to acute ischemia followed by
      reflow, is associated with irreversible loss (death) of cardiomyocytes. If left
      untreated, MI will lead to progressive loss of viable cardiomyocytes,
      deterioration of cardiac function, and congestive heart failure. While
      supplemental oxygen therapy has long been in practice to treat acute MI, there
      has not been a clear scientific basis for the observed beneficial effects.
      Further, there is no rationale for the amount or duration of administration of
      supplemental oxygenation for effective therapy. The goal of the present study was
      to determine an optimum oxygenation protocol that can be clinically applicable
      for treating acute MI. Using EPR oximetry, we studied the effect of exposure to
      supplemental oxygen cycling (OxCy) administered by inhalation of 21-100% oxygen
      for brief periods (15-90 min), daily for 5 days, using a rat model of acute MI.
      Myocardial oxygen tension (pO2), cardiac function and pro-survival/apoptotic
      signaling molecules were used as markers of treatment outcome. OxCy resulted in a
      significant reduction of infarct size and improvement of cardiac function. An
      optimal condition of 30-min OxCy with 95% oxygen + 5% CO2 under normobaric
      conditions was found to be effective for cardioprotection.

PMID- 30211172
TI  - Mechanical Circulatory Support for Single Ventricle Failure.
AB  - Mechanical circulatory support (MCS) for failing single ventricle (SV) physiology
      is a complex and challenging problem, which has not yet been satisfactorily
      addressed. Advancements in surgical strategies and techniques along with
      intensive care management have substantially improved the outcomes of neonatal
      palliation for SV physiology, particularly for hypoplastic left heart syndrome
      (HLHS). This is associated with a steady increase in the number of SV patients
      who are susceptible to develop heart failure (HF) and would potentially require
      MCS at a certain stage in their palliation. We have reviewed the literature
      regarding the reported modalities of MCS use in the management of SV patients.
      This includes analysis of various devices and strategies used for failing
      circulation at distinct stages of the SV pathway: after neonatal palliation,
      after the superior cavo-pulmonary connection (SCPC), and after total cavo
      pulmonary connection (TCPC).

PMID- 30211173
TI  - The Importance of Subchondral Bone in the Pathophysiology of Osteoarthritis.
AB  - Subchondral bone plays a critical role in the pathogenesis of osteochondral
      disease across veterinary species. The subchondral bone is highly adaptable, with
      the ability to model and remodel in response to loading stresses experienced by
      the joint. Repetitive stress injuries within the joint can result in primary or
      secondary pathologic lesions within the subchondral bone, which have been
      recognized to contribute to the development and progression of osteoarthritis.
      Recent advances in diagnostic imaging, particularly volumetric imaging modalities
      have facilitated earlier identification of subchondral bone disease. Despite
      these advancements, limitations in our knowledge about subchondral bone makes
      treatment and prevention of these conditions challenging. The purpose of this
      report is to review our current understanding of subchondral bone and its
      relationship to osteoarthritis across veterinary species, with a specific focus
      in the research that has been performed in horses. It can be concluded that our
      current understanding of subchondral bone is advancing, and future experimental,
      clinical and pathologic studies will provide additional insight about subchondral
      bone and its relationship to joint disease.

PMID- 30211169
TI  - Molecular Diagnostics in Clinical Oncology.
AB  - There are multiple applications of molecular tests in clinical oncology. Mutation
      analysis is now routinely utilized for the diagnosis of hereditary cancer
      syndromes. Healthy carriers of cancer-predisposing mutations benefit from tight
      medical surveillance and various preventive interventions. Cancers caused by germ
      line mutations often require significant modification of the treatment strategy.
      Personalized selection of cancer drugs based on the presence of actionable
      mutations has become an integral part of cancer therapy. Molecular tests underlie
      the administration of EGFR, BRAF, ALK, ROS1, PARP inhibitors as well as the use
      of some other cytotoxic and targeted drugs. Tumors almost always shed their
      fragments (single cells or their clusters, DNA, RNA, proteins) into various body
      fluids. So-called liquid biopsy, i.e., the analysis of circulating DNA or some
      other tumor-derived molecules, holds a great promise for non-invasive monitoring
      of cancer disease, analysis of drug-sensitizing mutations and early cancer
      detection. Some tumor- or tissue-specific mutations and expression markers can be
      efficiently utilized for the diagnosis of cancers of unknown primary origin
      (CUPs). Systematic cataloging of tumor molecular portraits is likely to uncover a
      multitude of novel medically relevant DNA- and RNA-based markers.

PMID- 30211174
TI  - Fecal Hyodeoxycholic Acid Is Correlated With Tylosin-Induced Microbiome Changes
      in Growing Pigs.
AB  - The changes in the gut microbiome play an important role in the promoting effects
      of antibiotics, such as tylosin, to the health, and productivity of farm animals.
      Microbial metabolites are expected to be key mediators between antibiotics
      induced microbiome changes and growth-promoting effects. The objective of this
      study was to extend the identification of tylosin-responsive microbes to the
      identification of tylosin-responsive metabolites in growing pigs. The feeding
      trial was conducted on a commercial farm using two pens of pigs fed diets with
      and without tylosin (40 mg/kg of diet). Fecal samples were collected from 10 pigs
      per pen at weeks 10, 13, 16, 19, and 22 of age, and subsequently analyzed using
      liquid chromatography-mass spectrometry (LC-MS) analysis. The multivariate model
      of LC-MS data showed that time-dependent changes occurred in the fecal metabolome
      of both control and tylosin-treated pigs. More importantly, the metabolomic
      profiles were similar between the tylosin treatment and control groups in weeks
      10 and 22, but diverged during weeks 13-19. Subsequent analyses of the fecal
      metabolites contributing to the separation of two groups of pigs showed that
      hyodeoxycholic acid (HDCA), together with tylosin and its metabolites in feces,
      was greatly increased during weeks 13-19 (P < 0.05) in the group of pigs fed
      tylosin. The integration of current metabolomics data and the microbiome data
      from a previous study revealed the consistency between HDCA and a specific genus
      of microbes in the Clostridia family. Further studies are required to determine
      the causative relations between tylosin-elicited changes in HDCA and the
      microbiome as well as the role of HDCA in the growth promoting effects of
      tylosin.

PMID- 30211175
TI  - Robustness of Eco-Epidemiological Capture-Recapture Parameter Estimates to
      Variation in Infection State Uncertainty.
AB  - Estimating eco-epidemiological parameters in free-ranging populations can be
      challenging. As known individuals may be undetected during a field session, or
      their health status uncertain, the collected data are typically "imperfect".
      Multi-event capture-mark-recapture (MECMR) models constitute a substantial
      methodological advance by accounting for such imperfect data. In these models,
      animals can be "undetected" or "detected" at each time step. Detected animals can
      be assigned an infection state, such as "susceptible" (S), "infected" (I), or
      "recovered" (R), or an "unknown" (U) state, when for instance no biological
      sample could be collected. There may be heterogeneity in the assignment of
      infection states, depending on the manifestation of the disease in the host or
      the diagnostic method. For example, if obtaining the samples needed to prove
      viral infection in a detected animal is difficult, this can result in a low
      chance of assigning the I state. Currently, it is unknown how much uncertainty
      MECMR models can tolerate to provide reliable estimates of eco-epidemiological
      parameters and whether these parameters are sensitive to heterogeneity in the
      assignment of infection states. We used simulations to assess how estimates of
      the survival probability of individuals in different infection states and the
      probabilities of infection and recovery responded to (1) increasing infection
      state uncertainty (i.e., the proportion of U) from 20 to 90%, and (2)
      heterogeneity in the probability of assigning infection states. We simulated
      data, mimicking a highly virulent disease, and used SIR-MECMR models to quantify
      bias and precision. For most parameter estimates, bias increased and precision
      decreased gradually with state uncertainty. The probabilities of survival of I
      and R individuals and of detection of R individuals were very robust to
      increasing state uncertainty. In contrast, the probabilities of survival and
      detection of S individuals, and the infection and recovery probabilities showed
      high biases and low precisions when state uncertainty was >50%, particularly when
      the assignment of the S state was reduced. Considering this specific disease
      scenario, SIR-MECMR models are globally robust to state uncertainty and
      heterogeneity in state assignment, but the previously mentioned parameter
      estimates should be carefully interpreted if the proportion of U is high.

PMID- 30211176
TI  - Working Dogs Drinking a Nutrient-Enriched Water Maintain Cooler Body Temperature
      and Improved Pulse Rate Recovery After Exercise.
AB  - Exercise-related physiological changes were evaluated in hydrated, exercise
      conditioned working dogs with free access to tap water (TW) with or without a
      nutrient-enriched water supplement (NW). Physiological samples and measures were
      collected before and after work-related field tasks in a warm and moderately
      humid ambient environment. In a cross-over design study, 12 dogs (age range 8-23
      months) were evaluated on 3 separate occasions within each period with exercise
      bouts up to 30 min, on days -4, 3, and 11. Dogs were offered either ad libitum TW
      or portion-controlled NW daily plus ad libitum TW. Prior to and serially after
      exercise, pulse rate (PR), core (BTcore) and ear (BTear) temperature were
      recorded. Urine was collected first thing in the morning, whereas blood samples
      collected and body weight (BW) recorded pre- and immediately post exercise.
      Ambient temperature was above 21.7 degrees C (71 degrees F) and relative humidity
      ranged from 36 to 76%. Activity parameters, AM urine measures, post-exercise
      percent change of BW, resting PR and resting BTcore did not differ between
      treatment groups on any exercise day. At the completion of exercise, mean BTcore
      for all dogs ranged from 104.8 to 105.6 degrees F. Immediate post-exercise BTear
      was always lower compared to BTcore and means ranged from 103.3 to 104.0 degrees
      F. The effect of time was highly significant (P < 0.001) for both BT measures
      with both BTcore and BTear recovering to resting levels by 60 min post exercise.
      PR and several blood values showed a significant main effect of time. Over the
      recovery period, dogs in the NW group had lower mean BTear and PR by 0.6 degrees
      F and 3.4 bpm, respectively. Daily ingestion of a NW in combination with free
      access to TW can reduce the post-exercise-related BTcore and BTear hyperthermia,
      and improve pulse rate recovery following exercise in this population of working
      dogs undergoing 30 min bout of exercise.

PMID- 30211178
TI  - Global perspectives on cardiometabolic risk and cardiovascular disease: from
      basic science to bedside.

PMID- 30211177
TI  - Evaluation of the Prevalence and Risk Factors for Undernutrition in Hospitalized
      Dogs.
AB  - Hospitalized dogs are predisposed to undernutrition, which can potentially affect
      outcome. This study evaluated the prevalence of undernutrition in hospitalized
      dogs (measured as loss of body condition score, BCS and body weight, BW) and
      studied the risk factors that affect nutritional status, and outcome (discharge
      or death). Data was collected prospectively during 9 months from 500 hospitalized
      dogs with a hospitalization length longer than 24 h in a veterinary teaching
      hospital in Spain. The BCS and BW changes were modeled using multiple linear
      regression and outcome was modeled using logistic regression. The risk factors
      studied were energy intake, hospitalization length, initial BW and BCS, age, sex,
      severity of clinical signs, department of admission, fasting or nutritional
      interventions, and the presence of anorexia, vomiting or diarrhea at admission.
      Most of the dogs (84.0%) consumed less than 25% of their energy requirements and
      only 3.4% of the dogs met these requirements. The majority of hospitalized dogs
      maintained their BCS (78.2%) and BW (77%) during hospitalization. Older patients
      (P = 0.040), higher initial BCS (P < 0.001), and vomiting at admission (P =
      0.030) were associated with a decrease of BCS status during hospitalization. BCS
      was also decreased in patients with low energy intake, particularly in patients
      with hospitalization length longer than 3 days (P < 0.001). Both longer
      hospitalization length (P < 0.001) and vomiting at admission (P = 0.004) were
      also associated with a decrease in BW. Dogs that consumed their theoretical
      energy requirements [P < 0.001; Odds Ratio (OR) 0.95, 95% CI: 0.92 to 0.98], and
      had a higher initial BCS (P < 0.001; OR 0.39, 95% CI: 0.22 to 0.63) had a lower
      odds of dying. Anorexia at admission (P < 0.001; OR 5.67, 95% CI: 2.23 to 15.47)
      was associated with a higher risk of death. The results from this study support
      the finding that undernutrition is relatively common during hospitalization, with
      age, hospitalization length, decreased energy intake, and vomiting at admission
      as risk factors for undernutrition. Furthermore, an association was found between
      inadequate energy intake and death.

PMID- 30211181
TI  - Improved identification of secondary hypertension: use of a systematic protocol.
AB  - Background: The accurate identification and diagnosis of secondary hypertension
      is critical, especially while atherosclerotic cardiovascular heart disease
      continues to be the leading cause of death in the industrialized world.
      Nevertheless, despite the existence of diagnostic tools, there are significant
      variations of the estimated prevalence of secondary hypertension, due to multiple
      etiologies and suboptimal recognition. This study demonstrates the results of
      using a systematic and protocolled approach to improve recognition of the
      presence of secondary hypertension. In the future, this questionnaire can be a
      quick and effective tool to unveil secondary hypertension in a broad array of
      clinical settings. Methods: A total of 28,633 consecutive patients from January
      1, 2007 to January 1, 2017 were diagnosed as having primary or secondary
      hypertension, utilizing the International Code of Diseases. Patients were located
      at the Center of Hypertension, Institute of Cardiology at Austral University
      Hospital, Buenos Aires, Argentina and were then further classified as having TRH,
      or non-resistant hypertension, to which a systematic protocol was employed in
      search for secondary hypertension. The confirmation of secondary hypertension was
      subsequently confirmed by diagnostic laboratory and imaging techniques in a
      hospital setting. Results: A final population of 12,284 patients with treatment
      resistant hypertension (TRH) and non-treatment resistant hypertension (NTRH) were
      included in this study, where an etiology of secondary hypertension was
      identified in 50.9% and 36% of patients in each treatment group, respectively.
      Physicians used confirmatory laboratory testing and imaging of patients who were
      identified as having a cause for their secondary hypertension, with no
      significant differences in sex, age and body mass index (BMI) among study groups.
      Conclusions: These results illustrate the prevalence and distribution of the
      causes of secondary hypertension using a systematic, protocolled approach, which
      revealed a higher percentage of secondary hypertension than previously reported.
      This tool may be used by healthcare providers to ensure the appropriate
      recognition of secondary causes of hypertension in a wider range of patients with
      high blood pressure beyond resistant hypertension, changing the diagnostic
      paradigm of this condition.

PMID- 30211180
TI  - Creatine kinase, energy reserve, and hypertension: from bench to bedside.
AB  - We hypothesized that human variation in the activity of the ATP regenerating
      enzyme creatine kinase (CK) activity affects hypertension and cardiovascular
      disease risk. CK is tightly bound close to ATP-utilizing enzymes including Ca2+
      ATPase, myosin ATPase, and Na+/K+-ATPase, where it rapidly regenerates ATP from
      ADP, H+, and phosphocreatine. Thus, relatively high CK was thought to enhance ATP
      demanding processes including resistance artery contractility and sodium
      retention, and reduce ADP-dependent functions. In a series of studies of our
      group and others, CK was linked to hypertension and bleeding risk. Plasma CK
      after rest, used as a surrogate measure for tissue CK, was associated with high
      blood pressure and failure of antihypertensive therapy in case-control and
      population studies. Importantly, high tissue CK preceded hypertension in animal
      models and in humans, and human vascular tissue CK gene expression was strongly
      associated with clinical blood pressure. In line with this, CK inhibition
      substantially reduced the contractility of human resistance arteries ex vivo. We
      also presented evidence that plasma CK reduced ADP-dependent platelet
      aggregation. In subsequent intervention studies, the oral competitive CK
      inhibitor beta-guanidinopropionic acid (GPA) reduced blood pressure in
      spontaneously hypertensive rats (SHRs), and a 1-week trial of sub-therapeutic
      dose GPA in healthy men was uneventful. Thus, based on theoretical concepts,
      evidence was gathered in laboratory, case-control, and population studies that
      high CK is associated with hypertension and with bleeding risk, potentially
      leading to a new mode of cardiovascular risk reduction with CK inhibition.

PMID- 30211179
TI  - Hypertension genomics and cardiovascular prevention.
AB  - Hypertension continues to be a major risk factor for global mortality, and recent
      genome-wide association studies (GWAS) have expanded in size, leading to the
      identification of further genetic loci influencing blood pressure. In light of
      the new knowledge from the largest cardiovascular GWAS to date, we review the
      potential impact of genomics on discovering potential drug targets, risk
      stratification with genetic risk scores, drug selection with pharmacogenetics,
      and exploring insights provided by gene-environment interactions.

PMID- 30211182
TI  - Advances in resistant hypertension.

PMID- 30211183
TI  - Cardio-metabolic disease in India-the up-coming tsunami.

PMID- 30211185
TI  - Hypertension and cardiovascular disease in the sub-Saharan African context.

PMID- 30211184
TI  - Unique approaches to hypertension control in China.
AB  - According to the China nationwide hypertension survey in 2012-2015, the
      prevalence of hypertension in adults (>=18 years) was 27.9%, which increased
      approximately by 50% from 2002 (18.8%). The management of hypertension was
      improved, but still at low level, with the awareness, treatment and control rates
      of 46.9%, 40.7% and 15.3%, respectively. The challenge was still the low
      awareness and the low control rate in treated hypertension (37.5%). Several
      actions are currently being taken to improve hypertension control in China. In
      collaboration with the International Society of Hypertension May Measurement
      Month (MMM) Program, hundreds of volunteers across the country measured blood
      pressure in a large number of people in summer since 2017. In addition, a
      nationwide Web-based and WeChat-linked blood pressure measurement system is being
      built, with thousands of devices installed in public places within easy-reach of
      people. To improve blood pressure control in treated hypertension, two
      initiatives are being undertaken. One is the expanding use of ambulatory blood
      pressure monitoring to guide antihypertensive treatment. Another is primary
      aldosteronism screen in resistant hypertension. It is hoped that in the framework
      of the Healthy China 2030 Program the control rate of hypertension may increase
      in the next 10 years to 50% or higher by increasing both the awareness rate in
      the population and control rate in treated hypertensive patients to 70% or
      higher.

PMID- 30211186
TI  - The economic case for US hospitals to revise their approach to heart failure
      readmission reduction.
AB  - To support hospital decision makers in their effort to reduce readmissions, the
      authors of this perspective present employer self-insurance as a potential
      incentive strategy, in particular for heart failure (HF). In 2010, US health
      reform identified hospital readmission as a key area for improving care
      coordination and achieving potential healthcare savings, and enacted the Hospital
      Readmissions Reduction Program (HRRP). In 2012, the Centers for Medicare and
      Medicaid Services (CMS) started the implementation of the HRRP by penalizing
      hospitals with excess 30-day readmission rates. The HRRP targets certain
      conditions, including HF, which is among the most expensive conditions treated in
      US hospitals. HF has the highest readmission rate for patients aged 65 and above,
      and its prevalence is expected to rise to over 8 million people by 2030 due to
      the aging population. Although the HRRP has been associated with reduced
      readmission rates, the rate of reduction has slowed. Furthermore, the HRRP may
      have alarming unintended consequences, such as possible increased mortality among
      HF patients. As a result, a critical analysis of financial incentives is needed
      to re-energize these efforts. One opportunity to incentivize readmission
      reduction is through employer self-insurance. More than half of colleges and
      universities self-insure the health care coverage they offer to their employees.
      With these self-insured plans, a hospital could be rewarded through shared
      savings with a university for readmission reduction. This perspective proposes
      that the economic case for a hospital to invest in readmission reduction is
      stronger when a hospital is a part of a self-insured university.

PMID- 30211187
TI  - Current concepts in the management of stable ischemic heart disease and acute
      coronary syndrome in patients with hemophilia.
AB  - Coronary artery disease (CAD), including stable ischemic heart disease (SIHD) and
      acute coronary syndrome (ACS), remains the leading cause of death in the US and
      one of the primary modalities used in the treatment of CAD is percutaneous
      coronary intervention (PCI). Despite the potential benefits of PCI in high risk
      CAD patients, the risk of hemorrhage presents a dilemma in the treatment of
      patients with hemophilia A and B. In an attempt to provide guidance on the
      management of SIHD and ACS in patients with hemophilia, we present the case of a
      patient with moderate hemophilia B and ACS who subsequently underwent PCI
      followed by a review of the associated literature.

PMID- 30211188
TI  - Physiologic assessment of moderate coronary lesions: a step towards complete
      revascularization in coronary artery bypass grafting.
AB  - Background: An accurate diagnostic assessment of coronary artery disease is
      crucial for patients undergoing coronary artery bypass grafting (CABG).
      Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) to guide
      complete revascularization have not been adequately studied in patients prior to
      CABG. We compared an anatomic to a physiologic assessment of moderate coronary
      lesions (40-70% stenosis) in patients referred for CABG. Methods: We
      retrospectively reviewed 109 medical records of patients who underwent CABG at
      Tulane Medical Center from 2014 to 2016. Patients were divided into an FFR/iFR
      guided and an angiography-guided group. Clinical characteristics, procedural
      outcomes, and clinical outcomes for the two groups were compared over an 18-month
      follow-up period. Results: There were significantly higher rates of three-vessel
      anastomoses (85.7% vs. 74.7%, P<0.05) and venous grafting (85.7% vs. 76.8%,
      P<0.05) in the FFR/iFR group. The FFR/iFR group had a lower rate of grafts placed
      to the left anterior descending artery (LAD) distribution than the angiography
      group (7.1% vs. 29.5%, P<0.05). The FFR/iFR group had a higher rate of grafts
      placed to the left circumflex (LCx) artery distribution than the angiography
      group (28.6% vs. 9.5%, P<0.05). We observed a trend toward reduction in major
      adverse cardiac events (MACEs) (7.1% vs. 11.6%, P=0.369) and angina (0.0% vs.
      6.3%, P=0.429) in the FFR/iFR group compared to the angiography group over 18
      months. Conclusions: Physiologic assessment of coronary lesions can effectively
      guide complete revascularization in patients undergoing CABG. Moreover, FFR/iFR
      guided CABG was associated with significantly higher rates of three-vessel
      anastomoses, venous grafting, and graft distribution to the circumflex system.

PMID- 30211189
TI  - Neurohormonal modulation as therapeutic avenue for right ventricular dysfunction
      in pulmonary artery hypertension: till the dawn, waiting.
AB  - Neuro-hormonal activation may lead to or be associated with pulmonary arterial
      hypertension (PAH) and right ventricular dysfunction. Notwithstanding whether it
      is the cause or the consequence of PAH-related right ventricle (RV) dysfunction
      neurohormonal activation contributes to significant morbidity and mortality in
      patients with PAH and the progression of RV dysfunction. Experimental data
      regarding the use of beta adrenergic blockade and renin-angiotensin aldosterone
      system modulation are encouraging. However, clinical studies have largely been
      negative or neutral; and, neuro-hormonal modulation is discouraged in patients
      with PAH related RV dysfunction for fear of systemic hypotension. Herein, we
      summarize the pathophysiological background that supports the potential role of
      neuro-hormonal modulation in the management of PAH related RV dysfunction; also
      present current clinical experience; and, discuss the need for controlled studies
      to move forward. Lastly, we review potential non- pharmacological modalities for
      neuro-hormonal modulations in PAH patients with RV dysfunction.

PMID- 30211190
TI  - Tumor stress-induced phosphoprotein 1 as a prognostic biomarker for breast
      cancer.
AB  - Background: Recent studies suggested an important relationship between tumor
      stress-induced phosphoprotein 1 (STIP1) and cancer. However, the expression of
      STIP1 in breast cancer tissues and its relationship with clinical characteristics
      and survival have not been investigated in humans. The aim of our work was to
      evaluate the association of STIP1 and the prognosis of breast cancer patients.
      Methods: The included patients were followed-up by telephone and through a review
      of their outpatient records. The expression of STIP1 was assessed by
      immunohistochemistry (IHC). The 5-year recurrence-free survival (RFS) rate and
      the 5-year overall survival (OS) rate were the prognostic indicators evaluated by
      the Kaplan-Meier method. Univariate and multivariate analyses employing a Cox
      regression model were used to calculate hazard ratios (HRs). Results: The rate of
      high expression of STIP1 was 55.3% (126/228) in breast cancer tissues and 14.9%
      (34/228) in adjacent normal tissues (chi2=81.495, P<0.001). High expression of
      STIP1 was associated with tumor size, stage and human epidermal growth factor
      receptor 2 (HER-2) status. The 5-year RFS rate was 75.4% in the STIP1 high
      expression group and 87.3% in the STIP1 low expression group (chi2=5.721,
      P=0.017). The 5-year OS rate was 84.1% in the STIP1 high expression group and
      94.1% in the STIP1 low expression group (chi2=5.814, P=0.016). STIP1 was found to
      be an independent relapse predictor for the adjusted HR is 1.983 (95% CI, 1.031
      3.815). Conclusions: High expression of STIP1 is associated with the poor
      prognosis of breast cancer patients and HER-2 positive expression. STIP1 may
      therefore serve as a prognostic biomarker for breast cancer patients.

PMID- 30211191
TI  - Prognostic value of circumferential resection margin in T3N0M0 esophageal
      squamous cell carcinoma.
AB  - Background: The prognostic value of positive circumferential resection margins
      (CRM) in resected esophageal squamous cell carcinoma (ESCC) is unclear. The Royal
      College of Pathologists criteria and the College of American Pathologists
      criteria are the two commonly used definitions of CRM involvement. The aim of
      this report was to compare the prognostic performance of the two criteria and to
      propose a modified stratification in patients who underwent radical esophagectomy
      for ESCC. Methods: We retrospectively reviewed 112 patients with pathologically
      confirmed T3N0M0 ESCC and without neoadjuvant therapy from June 2009 and July
      2011. The optimal cutoff point was obtained by the X-tile. The prognostic
      performance of different classifications of CRM was assessed in terms of
      homogeneity, discriminatory ability, and monotonicity. Results: According to the
      Royal College of Pathologists criteria, a positive CRM was detected in 87
      patients (77.7%); and 24 patients (21.4%) were found with positive CRM according
      to the College of American Pathologists criteria. Non-significant associations
      between overall survival and CRM were observed according to either of the two
      criteria. The analysis of reclassifying the CRM criteria demonstrated that the
      optimal cutoff CRM value for best prognostic power was 600 um. Patients with CRM
      more than 600 um showed better overall survival (P<0.05) than the cases with CRM
      less than 600 um. Furthermore, the improved homogeneity, discriminatory ability,
      and monotonicity gradients were also found in this modified criteria, as compared
      with the two existing criteria. Conclusions: Our study highlighted that CRM was
      an independent prognostic factor for survival in esophageal cancer patients, and
      the modified CRM criteria had better prognostic power than the traditional
      criteria in patients with ESCC.

PMID- 30211192
TI  - Prolonged dexmedetomidine infusion in critically ill adult patients: a
      retrospective analysis of a large clinical database Multiparameter Intelligent
      Monitoring in Intensive Care III.
AB  - Background: There is no conclusive evidence for the effects of prolonged infusion
      of dexmedetomidine in critically ill patients. We aimed to investigate the safety
      of long-term dexmedetomidine infusion in a large critically ill patients cohort
      from the Multiparameter Intelligent Monitoring in Intensive Care III (MIMIC-III)
      database. Methods: We retrospectively extracted records from MIMIC-III database.
      Dexmedetomidine administration time was the basis for group. Variables were
      compared by chi-square tests, and Mann-Whitney U test as appropriate. We used
      logistic regression model for multivariate analysis. Contour maps were drawn to
      measure rebound of heart rate (HR) and blood pressure (BP). Results: We finally
      got 1,946 records including 1,368 distinct individuals. Age, body mass index
      (BMI), length of stay in hospital, accumulated doses of dexmedetomidine and
      Sequential Organ Failure Assessment (SOFA) score were independent risk factors of
      in-hospital mortality (P<0.05). But prolonged dexmedetomidine infusion (>=24 h)
      and abrupt cessation did not increase in-hospital mortality. Furthermore, the
      rebound of HR and BP was more likely to occur in patients with prolonged infusion
      of dexmedetomidine. Conclusions: Prolonged dexmedetomidine infusion is not
      related to an increased in-hospital mortality, but it is associated with the
      rebound effect of HR and BP. Further prospective studies are needed.

PMID- 30211193
TI  - Thyroid stimulating hormone and free triiodothyronine are valuable predictors for
      diabetic nephropathy in patient with type 2 diabetes mellitus.
AB  - Background: Diabetes seriously threatens human health, and diabetic nephropathy
      (DN) is one of the serious diabetic complications. Therefore, it is valuable to
      predict the occurrence of DN early. This study aims to evaluate the predicting
      significance of thyroid hormones for DN. Methods: A total of 301 type 2 diabetes
      mellitus (T2DM) patients were enrolled. Thyroid hormones before treatment were
      measured, and the risk factors and their predicting significance for T2DM and DN
      were assessed. Results: The results indicated that there was no statistical
      difference in any investigated variable between controls and patients without
      complications (P>0.05). However, patients with DN exhibited lower levels of
      triiodothyronine (T3) and free triiodothyronine (FT3), but higher levels of
      thyroid stimulating hormone (TSH) than T2DM patients without complications
      (P<0.001). Multivariate analysis did not demonstrate any thyroid hormone as the
      independent risk factor for T2DM without complications, but revealed increased
      TSH and decreased T3 and FT3 as the independent risk factors for patients with DN
      [odds ratio (OR): 2.087, 95% CI: 1.525-3.303; 1.335, 95% CI: 1.101-1.621; 7.414,
      95% CI: 4.319-13.986; P<0.001, respectively]. The area under receiver operating
      characteristic (ROC) curve of TSH, FT3 and T3 was 0.850 (95% CI: 0.776-0.923),
      0.824 (95% CI: 0.751-0.897), and 0.620 (95% CI: 0.515-0.725) for DN prediction.
      Based on their cutoff values of 1.85 mIU/L, 2.31 ng/L, and 0.61 ug/L, the
      sensitivity was 82%, 78%, and 64%, and the specificity was 77%, 79%, and 85%,
      respectively. Conclusions: Our findings suggest that TSH and FT3 are useful
      predictors for DN in patients with T2DM.

PMID- 30211194
TI  - Two novel mutations in parE among Shigella flexneri isolated from Jiangsu
      Province of China, 2016.
AB  - Background: The study was conducted to assess the resistance capacity of
      quinolone against Shigella flexneri, and to investigate the involved quinolone
      resistance mechanism. The data were collected from Jiangsu Province, China in
      2016. Methods: The number of 81 S. flexneri was obtained from 12 cities in
      Jiangsu Province of China during 2016. Slide agglutination was taken for
      serotyping, and susceptibility test was identified by the disc diffusion method.
      PCR aimed to amplify the quinolone resistance-determining region (QRDR) genes and
      screen for plasmid-mediated quinolone resistance (PMQR) determinants. Chromosomal
      mutation was confirmed by sequencing and Blast comparison. Results: 2a was the
      commonest serotype, accounting for 40.7% (33/81) of the 81 S. flexneri. 70.4%
      (57/81) isolates expressed resistance against nalidixic acid, and the resistance
      against ciprofloxacin even reached up to a high proportion of 58.0% (47/81). A
      total of 8 point mutations were identified, including 2 novel mutations
      discovered in parE (Ser458Leu and Gly408Asp). The common mutation Ser83Leu in
      gyrA was still the most prevalent here with a percentage of 70.4% (57/81),
      followed by the approximate mutation of 69.1% (56/81) in parC (Ser80Ile) and
      His211Tyr in gyrA. Meanwhile, 35.8% (29/81) isolates were confirmed with mutation
      of Gln517Arg in gyrB. In addition, qnrS positive isolates occupied a proportion
      of 7.4% (6/81), but only 1 strain was observed with aac(6')-Ib-cr. All PMQR
      positive isolates were resistant to nalidixic acid. However, 5 of them didn't
      stay susceptible to ciprofloxacin any more. Conclusions: This is the first time
      that a study researches the occurrence of mutations in parE among S. flexneri,
      Ser458Leu and Gly408Asp included. The study indicates that the high resistance to
      fluoroquinolone remains a serious problem in Jiangsu, China. Thus, the prevention
      and control of current infection urge for a comprehensive and systematic
      surveillance based on persistent surveys.

PMID- 30211195
TI  - Autologous platelet-rich gel combined with in vitro amplification of bone marrow
      mesenchymal stem cell transplantation to treat the diabetic foot ulcer: a case
      report.
AB  - The diabetic foot ulcer (DFU) is the leading cause of the high mortality and
      morbidity rates of diabetes patients, and the DFU accounts for approximately 15%
      of all diagnosed diabetes cases in China. Traditional treatment is typically
      ineffective for DFUs. Here, we present a case of DFU that was successfully
      treated with an autologous platelet-rich gel (APG) and in vitro amplification of
      bone marrow mesenchymal stem cell (BMMSC) transplantation. A 54-year-old woman
      initially presented with a right foot diabetic ulcer at the hospital. A wound at
      the lateral malleolus of the right foot was observed with exudation and
      infection. The standard treatment included glucose reduction with insulin, blood
      lipid control with atorvastatin, circulation improvement with alprostadil, anti
      infection treatment with sensitive antibiotics, debridement, dressing, and
      continuous negative pressure suction, and after the standard treatment, the APG
      combined with in vitro amplification of BMMSC transplantation was used to help
      the healing of the ulcer. All of the above interventions may have contributed to
      the healing of the ulcer, and an APG combined with in vitro amplification of
      BMMSCs may promote DFU healing. The difficulty of DFU treatment remains a
      challenge, particularly in diabetic patients who develop foot ulcers, due to the
      complexity of its multifaceted pathogenesis. This case represents an effective
      adjuvant treatment for such patients.

PMID- 30211197
TI  - The usefulness of transient elastography in patients with autoimmune hepatitis
      when can we use it?

PMID- 30211196
TI  - Decision curve analysis: a technical note.
AB  - Multivariable regression models are widely used in medical literature for the
      purpose of diagnosis or prediction. Conventionally, the adequacy of these models
      is assessed using metrics of diagnostic performances such as sensitivity and
      specificity, which fail to account for clinical utility of a specific model.
      Decision curve analysis (DCA) is a widely used method to measure this utility. In
      this framework, a clinical judgment of the relative value of benefits (treating a
      true positive case) and harms (treating a false positive case) associated with
      prediction models is made. As such, the preferences of patients or policy-makers
      are accounted for by using a metric called threshold probability. A decision
      analytic measure called net benefit is then calculated for each possible
      threshold probability, which puts benefits and harms on the same scale. The
      article is a technical note on how to perform DCA in R environment. The decision
      curve is depicted with the ggplot2 system. Correction for overfitting is done via
      either bootstrap or cross-validation. Confidence interval and P values for the
      comparison of two models are calculated using bootstrap method. Furthermore, we
      describe a method for computing area under net benefit for the comparison of two
      models. The average deviation about the probability threshold (ADAPT), which is a
      more recently developed index to measure the utility of a prediction model, is
      also introduced in this article.

PMID- 30211198
TI  - Prof. Nico van Zandwijk: all forms of asbestos are carcinogenic and safe use of
      asbestos is an illusion.

PMID- 30211199
TI  - Dr. Xue Qin Yu: social determinants in health should be an important subject in
      medical education.

PMID- 30211200
TI  - Overcoming the limitations of glomerular filtration rate estimation by using a
      novel rapid bedside measurement?

PMID- 30211201
TI  - Pompe disease: how to solve many problems with one solution.

PMID- 30211202
TI  - Interactive translational research model and cadaveric simulation: where
      minimally invasive cardiac surgery and industry meet.
AB  - Focused research targeting an identified clinical problem may result in more
      rapid development of medical devices, technologies, and surgical techniques that
      directly impact patient care. These medical advances to improve patient care may
      be expedited by adopting an interactive translational research model in which
      inventors, designers, and engineers work in collaboration with surgeons. In
      addition, cadaveric simulation is a high-fidelity model that is bridging the
      translational and logistical gap to bring new surgical devices, technologies, and
      techniques to patients. We describe the partnership between the University of
      Rochester and LSI SOLUTIONS(r) in which an interactive translational research
      model utilizing cadaveric simulation has been successfully applied to accelerate
      bringing minimally invasive cardiac surgical techniques and innovative devices to
      patients.

PMID- 30211203
TI  - Hepatitis B virus-persistent infection and innate immunity defect: Cell-related
      or virus-related?
AB  - The outcomes of hepatitis B virus (HBV) infection are closely related to the age
      at which infection was acquired. Infection acquired in adult life tends to be
      self-limited, in contrast to perinatal acquirement, for which chronic persistence
      of the HBV is a general outcome. Innate immunity plays an indispensable role in
      early virus infection, facilitating virus clearance. However, it has been
      reported that HBV is under-recognized and poorly eliminated by the innate immune
      system in the early stages of infection, possibly explaining the long-lasting
      persistence of viremia afterwards. Furthermore, due to the existence of
      covalently closed circular DNA, chronic HBV clearance is very difficult, even
      when patients are given interferon-alpha and nucleotide/nucleoside analogs for
      antiviral therapy. The mechanism by which HBV evades innate immune recognition
      and establishes persistent infection remains a subject of debate. Besides, some
      researchers are becoming more interested in how to eradicate chronic HBV
      infection by restoring or boosting innate immunity. This review aimed to
      summarize the current knowledge on how intrahepatocyte signaling pathways and
      innate immune cells act after the onset of HBV infection and how these actions
      are related to the persistence of HBV. We anticipate the insights presented
      herein to be helpful for future development of novel immune therapeutic
      strategies to fight HBV infection.

PMID- 30211204
TI  - Diagnostic value of imaging examinations in patients with primary hepatocellular
      carcinoma.
AB  - Primary hepatocellular carcinoma (PHC) includes hepatocellular carcinoma,
      intrahepatic cholangiocarcinoma and other pathological types and is characterized
      by rapid progression. Most of the clinical diagnoses are made at late stage or
      when distant metastasis occurs, increasing the difficulty of treatment and
      resulting in a poor prognosis. Therefore, the early diagnosis of PHC plays an
      important role in timely treatment and the improvement of prognosis. The gold
      standard for the diagnosis of primary liver cancer is liver biopsy, but it has
      limitations as an invasive examination. Presently, imaging has become the first
      choice for the diagnosis of liver cancer. We here summarize the new methods and
      techniques of imaging in diagnosis and evaluation of primary liver cancer in
      recent years, including ultrasonography, computed tomography perfusion imaging,
      diffusion-weighted imaging technology-voxel incoherent motion, diffusion tensor
      imaging, iterative decomposition of water and fat with echo asymmetry and least
      squares estimation-iron quantification, dynamic enhanced magnetic resonance
      imaging and hepatocyte-specific contrast medium imaging. Imaging diagnosis can
      not only evaluate the degree of differentiation, blood supply and perfusion, and
      invasiveness of the lesion, but also predict the prognosis, evaluate liver
      function, and provide references for clinical diagnosis and treatment.

PMID- 30211205
TI  - Impact of sorafenib on epidural fibrosis: An immunohistochemical study.
AB  - AIM: To determine if sorafenib, an antineoplastic agent, could prevent the
      development of spinal epidural fibrosis (EF). METHODS: The study used CD105 and
      osteopontin antibodies in an immunohistochemical approach to quantify EF that
      occurred as a consequence of laminectomy in rats. Wistar albino rats (n = 16)
      were divided into two groups: control (L1-2 level laminectomy only) and sorafenib
      treatment (L1-2 level laminectomy + topical sorafenib). The animals were
      euthanatized after 6 wk, and the EF tissues were examined for histopathological
      changes after immunohistochemical staining. The EF grades were assigned to the
      tissues, and the treatment and control groups were compared. RESULTS: The EF
      thickness, inflammatory cell density, and arachnoid adherences determined by
      light microscopy were significantly higher in the control group compared to the
      sorafenib-treated group. Based on fibrosis scores, the extent of EF in the
      treatment group was significantly lower than in the controls. Immunohistochemical
      staining for CD105 to identify microvessels revealed that the EF grades based on
      vessel count were significantly lower in the treatment group. Staining for
      osteopontin did not show any significant differences between the groups in terms
      of the extent of EF. The staging of EF based on vascular counts observed after
      immunohistochemical staining for CD105, but not for osteopontin, was compatible
      with conventional staging methods. Neither toxic effects on tissues nor systemic
      side effects were observed with the use of sorafenib. CONCLUSION: Local
      administration of sorafenib significantly reduced post-laminectomy EF. Decreased
      neovascularization in spinal tissue may be due to the sorafenib-induced
      inhibition of vascular endothelial growth factor.

PMID- 30211208
TI  - Chronic carpal tunnel syndrome caused by covert tophaceous gout: A case report.
AB  - Carpal tunnel syndrome (CTS) is well recognized as the most common type of
      peripheral neuropathy. A rare cause of CTS is tophaceous gout. Tophi deposits can
      accumulate in various structures including the flexor tendons, tendon sheaths,
      the carpal tunnel floor, transverse carpal ligament, and even the median nerve,
      causing various symptoms such as pain, numbness, and weakness. Tophi forming in
      the carpal canal can compress the median nerve, leading to CTS. Here, we describe
      a 25-year-old male with a family history of tophaceous gout who presented with
      typical CTS symptoms. Although he had chronic numbness in his right hand, he
      failed to present with any obvious palpable masses on his forearm or hand.
      However, his family history, laboratory, clinical, and magnetic resonance imaging
      findings were consistent with tophi deposits. CTS symptoms were eased through
      surgical removal of tophi and decompression of the median nerve. No recurrences
      of gout and CTS symptoms were reported at a one-year follow-up. This case shows
      that CTS symptoms could be the initial manifestation of tophaceous gout. In
      patients with a family history of gout and with CTS symptoms, imaging
      examinations are critical for early diagnosis and selecting appropriate
      treatment. Surgical removal of "covert" tophi and decompression of the median
      nerve is an effective option for eliminating symptoms.

PMID- 30211207
TI  - Unexpected complication during extracorporeal membrane oxygenation support:
      Ventilator associated systemic air embolism.
AB  - Systemic air embolism through a bronchovenous fistula (BVF) has been described in
      patients undergoing positive-pressure ventilation. However, no report has
      mentioned the potential risks of systemic air embolism through a BVF in patients
      undergoing extracorporeal membrane oxygenation (ECMO). Positive-pressure
      ventilation and ECMO support in patients with lung injury can increase the risk
      of systemic air embolism through a BVF. Increased alveolar pressure, decreased
      pulmonary venous pressure, and anticoagulation are thought to be the factors that
      contribute to this complication. Here, we present a case of systemic air embolism
      in a patient with ECMO and mechanical ventilator support.

PMID- 30211209
TI  - Case report and review of the literature of primary gastrointestinal amyloidosis
      diagnosed with enteroscopy and endoscopic ultrasonography.
AB  - Here, we report a rare case of primary gastrointestinal amyloidosis in a stable
      condition after being followed up for three years. The patient was admitted to
      the hospital in 2014. Tests showed decreased levels of hemoglobin and ferritin.
      Transoral and transanal enteroscopy showed multiple nodular protuberances in the
      esophagus, ileum, colon and rectum. Endoscopic ultrasonography indicated the
      nodular protuberances stemmed from the submucosa and partially invaded the
      intrinsic myometrium. Pathological examinations found multiple small nodules in
      the submucosa and dyed structures, which were positive for special Congo red
      dyeing. After treatment with oral iron supplements, the levels of hemoglobin and
      ferritin became normal. It is concluded that the patient represents a case of
      primary gastrointestinal amyloidosis with multiple nodular protuberances in the
      digestive tract with controllable moderate abdominal discomfort and anemia and a
      benign course. Enteroscopy and endoscopic ultrasonography play an important role
      in the diagnosis of primary gastrointestinal amyloidosis.

PMID- 30211206
TI  - Conversion therapy and suitable timing for subsequent salvage surgery for
      initially unresectable hepatocellular carcinoma: What is new?
AB  - AIM: To review the conversion therapy for initially unresectable hepatocellular
      carcinoma (HCC) patients and the suitable timing for subsequent salvage surgery.
      METHODS: A PubMed search was undertaken from 1987 to 2017 to identify articles
      using the keywords including "unresectable" "hepatocellular carcinoma",
      "hepatectomy", "conversion therapy", "resection", "salvage surgery" and
      "downstaging". Additional studies were investigated through a manual search of
      the references from the articles. The exclusion criteria were duplicates, case
      reports, case series, videos, contents unrelated to the topic, comments, and
      editorial essays. The main and widely used conversion therapies and the suitable
      timing for subsequent salvage surgery were discussed in detail. Two members of
      our group independently performed the literature search and data extraction.
      RESULTS: Liver volume measurements [future liver remnant (FLR)/total liver volume
      or residual liver volume/bodyweight ratio] and function tests (scoring systems
      and liver stiffness) were often performed in order to justify whether patients
      were suitable candidates for surgery. Successful conversion therapy was usually
      defined as downstaging the tumor, increasing FLR and providing subsequent salvage
      surgery, without increasing complications, morbidity or mortality. The
      requirements for performing salvage surgery after transcatheter arterial
      chemoembolization were the achievement of a partial remission in radiology, the
      disappearance of the portal vein thrombosis, and the lack of extrahepatic
      metastasis. Patients with a standardized FLR (sFLR) > 20% were good candidates
      for surgery after portal vein embolization, while other predictive parameters
      like growth rate, kinetic growth rate were treated as an effective supplementary.
      There was probably not enough evidence to provide a standard operation time after
      associating liver partition and portal vein ligation for staged hepatectomy or
      yttrium-90 microsphere radioembolization. The indications of any combinations of
      conversion therapies and the subsequent salvage surgery time still need to be
      carefully and comprehensively evaluated. CONCLUSION: Conversion therapy is
      recommended for the treatment of initially unresectable HCC, and the suitable
      subsequent salvage surgery time should be reappraised and is closely related to
      its previous therapeutic effect.

PMID- 30211210
TI  - Acetaminophen-induced acute pancreatitis: A case report and literature review.
AB  - Acute pancreatitis is rarely associated with drugs. Acetaminophen overdose is a
      well-known cause of hepatic toxicity, but drug-induced pancreatitis is rarely
      reported, especially after mild overdose. A 32-year-old woman presented with
      nausea and vomiting for 12 h, but no abdominal pain following an overdose of
      eight Tylenol tablets containing acetaminophen (325 mg acetaminophen per tablet).
      Laboratory results on admission showed abnormal amylase and lipase levels but
      completely normal liver function. Magnetic resonance cholangiopancreatography
      revealed mild swelling of the pancreas without fluid collection around the
      pancreas. The patient complained of severe abdominal pain five days after
      admission when attempting to drink water and liquids. Eight days after admission,
      fluid around the pancreas was observed by computed tomography. The patient was
      subsequently diagnosed with acetaminophen-induced acute pancreatitis after
      exclusion of common causes. Routine treatment for pancreatitis and N
      acetylcysteine were administered to prevent disease progression. The patient was
      discharged in good condition.

PMID- 30211211
TI  - Polycystic kidney and hepatic disease 1 gene mutations in von Meyenburg
      complexes: Case report.
AB  - Von Meyenburg complexes (VMCs) are a rare type of ductal plate malformation. We
      herein report two Chinese families with VMCs, and the suspicious gene mutation of
      this disease. Proband A was a 62-year-old woman with abnormal echographic
      presentation of the liver. She received magnetic resonance imaging (MRI)
      examination and liver biopsy, and the results showed she had VMCs. Histologically
      proved hepatocellular carcinoma was found 1 year after the diagnosis of VMCs.
      Proband B was a 57-year-old woman with intrahepatic diffuse lesions displayed by
      abdominal ultrasonography. Her final diagnoses were VMCs, congenital hepatic
      fibrosis, and hepatitis B surface e antigen-negative chronic hepatitis B after a
      series of examinations. Then, all the family members of both proband A and
      proband B were screened for VMCs by MRI or ultrasonography. The results showed
      that four of the 11 family members from two families, including two males and two
      females, were diagnosed with VMCs. DNA samples were extracted from the peripheral
      blood of those 11 individuals of two VMCs pedigrees and subjected to polymerase
      chain reaction amplification of the polycystic kidney and hepatic disease 1
      (PKHD1) gene. Two different mutation loci were identified. Heterozygous mutations
      located in exon 32 (c.4280delG, p.Gly1427ValfsX6) in family A and exon 28
      (c.3118C>T, p.Arg1040Ter) in family B were detected. We speculate that PKHD1 gene
      mutations may be responsible for the development of VMCs.

PMID- 30211212
TI  - Clival metastasis of renal clear cell carcinoma: Case report and literature
      review.
AB  - The clivus is an atypical metastatic site for renal clear cell carcinoma (RCCC).
      Here we report a 54 year old man with acute cavernous sinus syndrome. Brain
      magnetic resonance imaging identified a clival-based lesion with associated bony
      erosion. The patient underwent endoscopic endonasal biopsy and partial resection
      of the clival mass. Because histologic examination of the resected specimen
      resulted in a diagnosis of RCCC, contrast-enhanced computed tomography scan of
      the abdomen was performed and showed an enhanced left renal mass. The patient
      subsequently underwent laparoscopic left radical nephrectomy and gamma knife was
      planned for the residual clival lesion. We also retrospectively reviewed
      available published reports on clival metastases, specifically those from RCCC,
      since 1990.

PMID- 30211215
TI  - Erratum to "Prevalence and Associated Factors of Tuberculosis in Prisons Settings
      of East Gojjam Zone, Northwest Ethiopia".
AB  - [This corrects the article DOI: 10.1155/2017/3826980.].

PMID- 30211214
TI  - Whole Exome Sequencing Uncovers Germline Variants of Cancer-Related Genes in
      Sporadic Pheochromocytoma.
AB  - Background: Pheochromocytomas (PCCs) show the highest degree of heritability in
      human neoplasms. However, despite the wide number of alterations until now
      reported in PCCs, it is likely that other susceptibility genes remain still
      unknown, especially for those PCCs not clearly syndromic. Methods: Whole exome
      sequencing of tumor DNA was performed on a set of twelve PCCs clinically defined
      as sporadic. Results: About 50% of PCCs examined had somatic mutations on the
      known susceptibility VHL, NF1, and RET genes. In addition to these driver events,
      mutations on SYNE1, ABCC10, and RAD54B genes were also detected. Moreover,
      extremely rare germline variants were present in half of the sporadic PCC samples
      analyzed, in particular variants of MAX and SAMD9L were detected in the germline
      of cases wild-type for mutations in the known susceptibility genes. Conclusions:
      Additional somatic passenger mutations can be associated with known
      susceptibility VHL, NF1, and RET genes in PCCs, and a wide number of germline
      variants with still unknown clinical significance can be detected in these
      patients. Therefore, many efforts should be aimed to better define the
      pathogenetic role of all these germline variants for discovering novel potential
      therapeutic targets for this disease still orphan of effective treatments.

PMID- 30211216
TI  - Effects of Conventional Synthetic Disease-Modifying Antirheumatic Drugs on
      Response to Periodontal Treatment in Patients with Rheumatoid Arthritis.
AB  - Rheumatoid arthritis (RA) and periodontitis are common chronic inflammatory
      diseases and periodontitis is known to be more common and more severe in patients
      with RA. Based on a paucity of studies about the relationship between common
      conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and
      periodontitis, this prospective study aimed to evaluate the adjunctive effect of
      csDMARDs on response to nonsurgical periodontal treatment in patients with RA.
      Thirty-two patients with RA (RA group) and 32 systemically healthy patients
      (control group) with periodontitis were included in this study. The RA group
      patients were treated with csDMARDs, such as methotrexate, hydroxychloroquine,
      and sulfasalazine. Conventional nonsurgical periodontal treatment with scaling
      and root planing was performed in both groups. The extent and severity of
      periodontitis were evaluated by plaque index (PI), gingival index (GI), probing
      depth (PD), clinical attachment level (CAL), and bleeding on probing (BOP) at
      baseline and 4 weeks after periodontal treatment. There was no statistically
      significant difference of periodontal parameters between the RA and control
      groups at baseline. Four weeks after scaling and root planing, PD reduction, and
      CAL gain were higher in the RA group treated with csDMARDs compared to the
      control group, and the difference was statistically significant (P = 0.006 and
      0.003, respectively). A post hoc analysis of the RA group showed no statistically
      significant difference on the response to nonsurgical periodontal treatment in
      multiple csDMARDs therapy and addition of NSAIDs and/or steroids to csDMARDs. In
      patients with RA, csDMARDs showed beneficial effect on periodontal clinical
      parameters following the nonsurgical periodontal treatment.

PMID- 30211213
TI  - Metagenomic Approaches for Understanding New Concepts in Microbial Science.
AB  - Over the past thirty years, since the dawn of metagenomic studies, a completely
      new (micro) universe was revealed, with the potential to have profound impacts on
      many aspects of the society. Remarkably, the study of human microbiome provided a
      new perspective on a myriad of human traits previously regarded as solely (epi-)
      genetically encoded, such as disease susceptibility, immunological response, and
      social and nutritional behaviors. In this context, metagenomics has established a
      powerful framework for understanding the intricate connections between human
      societies and microbial communities, ultimately allowing for the optimization of
      both human health and productivity. Thus, we have shifted from the old concept of
      microbes as harmful organisms to a broader panorama, in which the signal of the
      relationship between humans and microbes is flexible and directly dependent on
      our own decisions and practices. In parallel, metagenomics has also been playing
      a major role in the prospection of "hidden" genetic features and the development
      of biotechnological applications, through the discovery of novel genes, enzymes,
      pathways, and bioactive molecules with completely new or improved biochemical
      functions. Therefore, this review highlights the major milestones over the last
      three decades of metagenomics, providing insights into both its potentialities
      and current challenges.

PMID- 30211218
TI  - Liver Retraction Using n-Butyl-2-Cyanoacrylate (NBCA) Glue during Laparoscopic
      Splenectomy and Azygoportal Disconnection in Cirrhotic Patients.
AB  - Background: Although liver retraction using n-butyl-2-cyanoacrylate (NBCA) glue
      has been applied to laparoscopic upper abdominal surgery in noncirrhotic
      patients, there is still no consensus on its safety and feasibility for cirrhotic
      patients. In this study, we aimed to investigate the safety and effectiveness of
      liver retraction using NBCA glue during laparoscopic splenectomy and azygoportal
      disconnection (LSD) for gastroesophageal varices and hypersplenism secondary to
      liver cirrhosis and portal hypertension. Methods: Thirty-nine gastroesophageal
      varices and hypersplenism secondary to liver cirrhosis and portal hypertension
      patients were included in our study. We performed LSD in the presence of NBCA
      glue (n = 22, NBCA group) and absence of NBCA glue (n = 17, n-NBCA group),
      respectively. The operation time, blood loss, postoperative hospitalization, and
      liver function were compared between the two groups. Results: There was no
      mortality during the operation. One patient in non-NBCA group received open
      surgery due to parenchyma hemorrhage. Postoperative pleural effusion occurred in
      2 cases of the NBCA group and 1 of the non-NBCA group. One showed left subphrenic
      abscess in the non-NBCA group. No postoperative bleeding occurred after 9-30
      months of follow-up. The time of operation in NBCA group was significantly
      shorter than those in n-NBCA group (198.86+/-17.86 versus 217.81+/-20.25min,
      P<0.01). Blood loss in NBCA group was significantly lower than non-NBCA group
      (159.09+/-56.98 versus 212.50+/-88.51 ml, P<0.05). The levels of alanine
      aminotransferase (ALT) and aspartate aminotransferase (AST) were increased on day
      1 after LSD and decreased to normal level on day 7 after LSD in both groups.
      There was no significant difference in postoperative hospitalization and liver
      function between the two groups. Conclusion: Liver retraction using NBCA glue
      during LSD for gastroesophageal varices and hypersplenism secondary to liver
      cirrhosis and portal hypertension is safe, effective, and feasible.

PMID- 30211219
TI  - Preoperative Evaluation of Soleal Vein Diameter by Ultrasound Is Beneficial for
      Prophylaxis of Deep Vein Thrombosis after Total Knee or Hip Arthroplasty.
AB  - Purpose: The purpose of this retrospective study was to determine the association
      between preoperative soleal vein (SV) diameter and deep vein thrombosis (DVT)
      following total joint arthroplasty (TJA). Methods: A total of 402 patients were
      enrolled, with 229 patients undergoing total knee arthroplasty (TKA) and 173
      patients undergoing total hip arthroplasty (THA). Ultrasonography was performed 1
      3 days preoperatively, on postoperative days 1, 3, and 7, or before discharge and
      during follow-up. The SV diameter was assessed preoperatively. Univariate
      analysis and multivariate logistic regression analysis were used to compare
      parameters between the DVT group and the non-DVT group. Results: 78 patients
      (19.4%) were found to have DVT during hospitalization and after discharge and 14
      patients (3.5%) developed symptomatic DVT. Multiple regression analysis showed
      that SV diameter, advanced age, and surgery type were independent predictors of
      postoperative DVT. In the logistic regression analysis for symptomatic DVT, SV
      diameter was found to be the only predictor. In the receiver operating
      characteristics (ROC) analysis for the value of SV diameter in diagnosing DVT,
      the area under curve (AUC) was 0.701 ((95% CI 0.636-0.766), P<0.001) and when the
      cut-off value of SV diameter was set at 0.57 cm, the sensitivity and specificity
      of SV diameter were 62.7% and 72.1%, respectively. Conclusions: SV diameter was
      an independent risk factor for total and symptomatic DVT after TJA. Preoperative
      ultrasound screening of the SV diameter may be beneficial for the prevention of
      postoperative DVT.

PMID- 30211217
TI  - Absorption of Codonopsis pilosula Saponins by Coexisting Polysaccharides
      Alleviates Gut Microbial Dysbiosis with Dextran Sulfate Sodium-Induced Colitis in
      Model Mice.
AB  - Objectives: Inflammatory Bowel Disease (IBD) is an autoimmune disease, and the
      gut microbiota has become a new therapeutic target. Herbal medicine (HM) has
      shown good efficacy in the clinical treatment of IBD; however, the synergistic
      actions of the dominant chemicals in HM decoctions are unclear. Methods: In this
      study, we explored whether the complicated interconnections between HM and the
      gut microbiota could allow crosstalk between HM ingredients. Saponins and
      polysaccharides, i.e., the dominant chemicals in the Codonopsis pilosula Nannf
      (CPN) decoction, were investigated in a dextran sulfate sodium- (DSS-) induced
      mouse model. Bacterial 16S rRNA sequencing analyzed the change of gut microbiota
      structure and diversity. Gas chromatography (GC) determined the content of short
      chain fatty acids (SCFAs) in feces. ELISA detected the expression of
      proinflammatory and anti-inflammatory cytokines associated with TH17/Treg
      balance. UPLC-QTOF-MS technology combined with PKsolver software analyzed the
      absorption of the highest exposure for monomeric compounds of CPN saponins in
      serum. The results indicated that CPN polysaccharides showed prebiotic-like
      effects in mice with DSS-induced colitis by simultaneously stimulating the growth
      of three important probiotics, i.e., Bifidobacterium spp., Lactobacillus spp.,
      and Akkermansia spp., and inhibiting the growth of pathogenic bacteria, including
      Desulfovibrio spp., Alistipes spp., and Helicobacter spp. Moreover, CPN
      polysaccharides improved intestinal metabolism, enhanced the production of short
      chain fatty acids, upregulated the expression of anti-inflammatory cytokines and
      downregulated the secretion of proinflammatory cytokines correlated with
      Th17/Treg balance, promoted the absorption of certain CPN saponins in the serum,
      and stimulated recovery of the holistic gut microbiota. Conclusion: CPN
      polysaccharides have the good prebiotic properties and shown good application
      prospects in the prevention and treatment of acute colitis. These findings
      provide insights into the specific bacteria responsible for active, inactive
      biotransformation of HM ingredients and those that are altered by HM
      administration.

PMID- 30211220
TI  - Changes in Liver Gene Expression and Plasma Concentration of Rbp4, Fetuin-A, and
      Fgf21 in Sprague-Dawley Rats Subjected to Different Dietary Interventions and
      Bariatric Surgery.
AB  - Purpose: To study the effect of duodenal-jejunal omega switch (DJOS) in
      combination with different dietary patterns on the retinol-binding protein
      (RBP4), fetuin-A, and fibroblast growth factor 21 (FGF21) plasma levels and their
      hepatic gene expressions in rats. Methods: A high-fat diet (HF) was given to 28
      rats and 28 more were fed with a control diet (CD) for 2 months. After that, half
      of each group underwent either DJOS or SHAM surgery. For the next 2 months, half
      of the animals in each operation group were kept on the same diet as before and
      half of them had the diet changed. After 16 weeks of the experiment RBP4, fetuin
      A, and FGF21 plasma levels as well as liver Rbp4, Ahsg, and Fgf21 gene
      expressions were measured. Results: DJOS had a reductive impact on plasma levels
      of RBP4, fetuin-A, and FGF21 and Rbp4, Ahsg, and Fgf21 relative gene expression
      in the liver when compared to SHAM. The HF/HF group expressed significantly
      higher RBP4 and fetuin-A plasma levels in comparison to the control. The HF diet
      used before and/or after surgery led to upregulation of Rbp4, Ahsg, and Fgf21
      relative gene expression. The lowest levels of analyzed parameters were observed
      in the CD/CD group. Conclusions: The efficiency of DJOS surgery, measured by
      hepatokines' plasma levels and their gene expressions in the liver, depends on
      the type of diet applied before and after surgery. Manipulation of dietary
      patterns can lead to marked improvements in metabolic profile after DJOS surgery.

PMID- 30211222
TI  - Role of the CHADS2 Score in the Evaluation of Carotid Atherosclerosis in Patients
      with Atrial Fibrillation Undergoing Carotid Artery Ultrasonography.
AB  - Objective: This study investigated the characteristics of carotid atherosclerosis
      in patients with atrial fibrillation (AF) and determined the feasibility and
      significance of the CHADS2 score in predicting the degree of carotid
      atherosclerosis. Methods: Consecutive patients (n = 109) with nonvalvular AF were
      registered and classified into two groups, the paroxysmal AF group (n = 59) and
      persistent AF group (n = 50). Fifty healthy patients, matched by sex and age,
      were considered the control group. All patients were examined using carotid
      ultrasound and velocity vector imaging (VVI). Results: Compared with the control
      group, the mean intimal-medial thickness in the paroxysmal AF group (0.56 +/-
      0.11 versus 0.61 +/- 0.10, respectively, P < 0.05) and the persistent AF group
      (0.56 +/- 0.11 versus 0.64 +/- 0.13, respectively, P < 0.001) was significantly
      increased. The plaque index (PI) in the persistent AF group was significantly
      higher than that observed in the paroxysmal AF group (1.05 +/- 1.33 versus 1.42
      +/- 1.47, respectively, P < 0.001). Regarding the VVI indices, those reflecting
      the long-axis longitudinal motion function of carotid arteries were significantly
      decreased in both AF groups. Compared with the control group, a significantly
      lower total longitudinal displacement (tLoD) index was observed in the persistent
      AF group (0.73 +/- 0.66 versus 0.31 +/- 0.23, respectively, P < 0.0001) and the
      paroxysmal AF group (0.73 +/- 0.66 versus 0.34 +/- 0.17, P < 0.0001). The CHADS2
      score was related to indicators reflecting the structure and function of the
      carotid artery. Conclusions: Carotid arterial structure and function were
      significantly altered in patients with AF. The degree of carotid atherosclerosis
      depended on the duration of AF. The CHADS2 score may be useful as a predictor of
      the extent of carotid atherosclerosis in patients with AF.

PMID- 30211221
TI  - Conservative Surgical Treatment of Bisphosphonate-Related Osteonecrosis of the
      Jaw with Er,Cr:YSGG Laser and Platelet-Rich Plasma: A Longitudinal Study.
AB  - Introduction: The management of bisphosphonate-related osteonecrosis of the jaw
      (BRONJ), with no evidence-based guidelines, remains controversial. We aimed to
      evaluate the efficiency of a conservative surgical treatment combining Er,Cr:YSGG
      laser and platelet-rich plasma (PRP) for the treatment of BRONJ in cancer
      patients. Methods: We performed a longitudinal cohort study. Inclusion criteria
      were (1) age >= 18 years; (2) cancer diagnosis; (3) treatment with NBP because of
      the underlying cancer. Results: We consecutively recruited ten patients diagnosed
      with BRONJ in stage I or II. These patients underwent a surgical laser-assisted
      therapy together with autologous PRP. At the latest follow-up at 12 months,
      clinical improvement was observed in eight patients. Registration Number is
      IRCT20180329039159N1. Conclusion: We could successfully manage the BRONJ
      utilizing this combined protocol to heal the 30% of surgically treated sites and
      to improve the 50% of patients' lesions clinically. Our findings suggest that a
      surgical approach combined with Er,Cr:YSGG laser and PRP benefit cancer patients
      with general health issues.

PMID- 30211223
TI  - Optimization of Fluorescent Labeling for In Vivo Nanoimaging of Sarcomeres in the
      Mouse Heart.
AB  - The present study was conducted to systematically investigate the optimal viral
      titer as well as the volume of the adenovirus vector (ADV) that expresses alpha
      actinin-AcGFP in the Z-disks of myocytes in the left ventricle (LV) of mice. An
      injection of 10 MUL ADV at viral titers of 2 to 4 * 1011 viral particles per mL
      (VP/mL) into the LV epicardial surface consistently expressed alpha-actinin-AcGFP
      in myocytes in vivo, with the fraction of AcGFP-expressing myocytes at ~10%. Our
      analysis revealed that SL was ~1.90-2.15 MUm upon heart arrest via deep
      anesthesia. Likewise, we developed a novel fluorescence labeling method of the T
      tubular system by treating the LV surface with CellMask Orange (CellMask). We
      found that the T-tubular distance was ~2.10-2.25 MUm, similar to SL, in the
      healthy heart in vivo. Therefore, the present high-precision visualization method
      for the Z-disks or the T-tubules is beneficial to unveiling the mechanisms of
      myocyte contraction in health and disease in vivo.

PMID- 30211224
TI  - Corrigendum to "Circulating Endocannabinoids and Insulin Resistance in Patients
      with Obstructive Sleep Apnea".
AB  - [This corrects the article DOI: 10.1155/2016/9782031.].

PMID- 30211225
TI  - Corrigendum to "Determination of Serum Lost Goodwill Target Proteome in Patients
      with Severe Traumatic Brain Injury".
AB  - [This corrects the article DOI: 10.1155/2015/183821.].

PMID- 30211226
TI  - Comment on "Effect of Riociguat and Sildenafil on Right Heart Remodeling and
      Function in Pressure Overload Induced Model of Pulmonary Arterial Banding".

PMID- 30211227
TI  - Epidemiology of Traffic Fatalities among Motorcycle Users in East Azerbaijan,
      Iran.
AB  - Background: The aim of this study was to determine some epidemiological aspects
      of motorcycle user traffic fatalities including the crash mechanisms and injury
      patterns in East Azerbaijan, Iran (2006-2016). Methods: A total of 1840
      motorcycle user mortal cases registered in East Azerbaijan forensic medicine
      database, in Iran, were analyzed over the time period between March 2006 and
      March 2016. The distribution and associations of both victim- and crash-related
      variables such as crash mechanism, types of involved vehicles, types of injuries,
      and demographic characteristics were investigated. Data were analyzed by Stata
      v.13 statistical software package. Results: Of the 9435 RTI deaths, 1840 (19.5%)
      were motorcycle users of whom 96.5% were male (mean age of 32.3 +/- 18.5 years).
      The majority of accident mechanisms were motorcycle-vehicle crashes (77.8%),
      followed by rollover (11.8%). Cars were the leading counterpart crash vehicle
      comprising about 34.8% of the motorcycle user mortalities. Inner city traffic
      injuries were the reason for 744 (40.7%) of the motorcycle user mortalities. Head
      trauma was the main cause of death. About 82% of the victims were motorcycle
      riders and the remainder were pillion passengers. A decreasing trend of fatal
      traffic accidents was observed over the study period for both the motorcycle user
      fatalities and other traffic injuries. The percentage of motorcycle mortalities
      over all traffic mortalities had a decreasing trend over the past nine years from
      March 2007 to March 2016 reaching a figure as low as 15.2% through the last year
      of study. Conclusions: Motorcycle traffic fatalities, although having a
      decreasing trend during the last decade with a better slope than most other
      traffic injuries, remain to be a major public health in north-west of Iran. There
      is a need for effective interventional programs to reduce the burden of
      motorcycle fatalities.

PMID- 30211228
TI  - Evaluation of the Pharmacokinetics and Hepatoprotective Effects of Phillygenin in
      Mouse.
AB  - Phillygenin is a bioactive intergradient in Osmanthus fragrans, a well-known food
      additive and Chinese traditional medicine. This study was to investigate the
      hepatoprotective effects and pharmacokinetics of phillygenin. The
      hepatoprotective effect of phillygenin was assessed in carbon tetrachloride-
      (CCl4-) intoxicated mice by monitoring levels of serum and tissue biomarkers. The
      pharmacokinetics of phillygenin was evaluated in the mouse after oral (po, 24 mg
      / kg) or intravenous (iv, 12 mg/kg) administration. Results showed that
      phillygenin has a great hepatoprotective effect on CCl4-induced liver injury in
      mice owing to its antioxidant activity and inhibition on cytochrome P450
      2E1(CYP2E1). After oral administration, phillygenin was efficiently absorbed with
      the oral bioavailability of 56.4%. Two metabolites, hydroxylated and dimethylated
      phillygenin, were identified in mouse urine. These results suggested that
      phillygenin could be explored as new and potential natural antioxidants and
      hepatoprotective agents.

PMID- 30211229
TI  - Divergent Evolutional Mode and Purifying Selection of the KIT Gene in European
      and Asian Domestic Pig Breeds.
AB  - The recent geographic expansion of wild boars and the even more recent
      development of numerous domestic pigs have spurred exploration on pig domestic
      origins. The porcine KIT gene has been showed to affect pleiotropic effects,
      blood parameters, and coat colour phenotypes, especially the white colour
      phenotype formation in European commercial breeds. Here, we described the use of
      SNPs to identify different selection patterns on the porcine KIT gene and the
      phylogenetic relationships of the inferred haplotypes. The phylogenetic tree
      revealed four clades in European and Asian wild and domestic pigs: two major
      clades with European and Asian origins and one minor clade with Iberian origins
      as well as the other minor clade in Asia, consistent with the major introgression
      of domestic Asian pigs in Europe around 18th -19th century. The domestication
      history of pigs, which occurred in the domestication centers (Europe and Asia),
      has also been demonstrated by mtDNA analysis. Furthermore, both Asian and
      European domestic pigs evolved under purifying selection. This study indicated
      that domestic pigs in Europe and Asia have different lineage origins but the
      porcine KIT gene was undergoing a purifying selection during their evolutional
      histories.

PMID- 30211230
TI  - Assessment of Biochemical and Densitometric Markers of Calcium-Phosphate
      Metabolism in the Groups of Patients with Multiple Sclerosis Selected due to the
      Serum Level of Vitamin D3.
AB  - Background: In addition to the widely known effect of vitamin D3 (vitD3) on the
      skeleton, its role in the regulation of the immune response was also confirmed.
      Aim: The assessment of biochemical and densitometric markers of calcium-phosphate
      metabolism in the groups of patients with relapsing-remitting multiple sclerosis
      (RRMS) selected due to the serum level of vitamin D3. Methods: The concentrations
      of biochemical markers and indices of lumbar spine bone densitometry (DXA) were
      determined in 82 patients divided into vitamin D3 deficiency (VitDd),
      insufficiency (VitDi), and normal vitamin D3 level (VitDn) subgroups. Results:
      The highest level of the parathyroid hormone (PTH) and the highest prevalence of
      hypophosphatemia and osteopenia were demonstrated in VitDd group compared to
      VitDi and VitDn. However, in VitDd, VitDi, and VitDn subgroups no significant
      differences were observed in the levels of alkaline phosphatase (ALP) and ionized
      calcium (Ca2+) and in DXA indices. A negative correlation was observed between
      the level of vitamin D3 and the Expanded Disability Status Scale (EDSS) in the
      whole MS group. The subgroups were significantly different with respect to the
      EDSS scores and the frequency of complaints related to walking according to the
      EQ-5D. Conclusions: It is necessary to assess calcium-phosphate metabolism and
      supplementation of vitamin D3 in RRMS patients. The higher the clinical stage of
      the disease assessed with the EDSS, the lower the level of vitamin D3 in blood
      serum. Subjectively reported complaints related to difficulties with walking were
      reflected in the EDSS in VitDd patients.

PMID- 30211231
TI  - Relationships of Insulin Action to Age, Gender, Body Mass Index, and Waist
      Circumference Present Diversely in Different Glycemic Statuses among Chinese
      Population.
AB  - Introduction: To study the influence of different glycemic statuses on the
      relationship of insulin action to age, gender, body mass index (BMI), waist
      circumference (WC), and waist-to-height ratio (WHtR) among Chinese population.
      Methods: A total of 35,327 participants (17,456 males and 17,871 females) were
      included in this nationally representative cross-sectional study. Glycemic status
      was defined according to the 2010 American Diabetes Association criteria. Fasting
      insulin was measured by the chemiluminescence method. Results: Insulin and HOMA
      IR levels were the highest in newly diagnosed diabetes and were lowest in normal
      fasting glucose (NFG) (P < 0.001). Insulin and HOMA-IR levels were higher in
      females (P < 0.001) than in males with previously diagnosed diabetes and impaired
      fasting glucose (IFG) and NFG, meanwhile decreased with age (P < 0.001) among IFG
      and NFG participants. As compared with participants with a BMI from 18.5 to 19.9,
      those in the lowest BMI category (<18.5) had a significantly elevated risk of IR
      (OR, 1.96; 95% CI, 1.01-3.80), as did those in the higher BMI categories among
      NFG participants. The risk of IR increased with WC and WHtR, and the response was
      linear (P < 0.001 for linear trend) for the participants with NFG but not in
      those with IFG. Conclusions: Different glycemic statuses significantly affect the
      relationships of insulin action to age, gender, BMI, WC, and WHtR among Chinese
      population.

PMID- 30211235
TI  - Validating a Drug-Related Problems Classification System in Outpatient Setting in
      Iran.
AB  - Objective: Medication Therapy Management service (MTMs) has been introduced to
      improve cooperation among pharmacists and other healthcare professionals in the
      management of chronic diseases, drug therapy, and patients on polypharmacy. One
      part of MTMs is detection and resolution of possible drug-related problems
      (DRPs). Nowadays, numerous DRPs classification systems are available, but due to
      some defects none of them are currently accepted and implemented universally. The
      purpose of this study is to design and validate a comprehensive system for
      classification and documentation of possible DRPs for the Iranian patients.
      Methods: In this methodological study, four classification systems were studied,
      and their differences were reviewed, compared. Ultimately, a comprehensive
      documentation system was developed and tested for validity using experts'
      opinions. Findings: A comprehensive list of 53 DRPs under eight categories was
      developed and examined for validity. After collecting the data and validity
      assessment, questions with content validity ratio of <0.4 and content validity
      index of <70% were excluded and modified. Finally, with the exclusion and
      modification of eight DRPs, a modified DRPs list was created. Conclusion:
      According to the universality and validity assessment and based on consensus of
      20 experts, this DRPs list can be used to regulate the standard operation
      procedure of outpatient clinics in Iran, and could act toward standardization of
      this service.

PMID- 30211233
TI  - The Genetic Polymorphisms of NLRP3 Inflammasome Associated with T Helper Cells in
      Patients with Multiple Myeloma.
AB  - The pathogenesis of multiple myeloma (MM) remains unclear and the NLRP3
      inflammasome has been more and more recognized in the progression of many
      diseases. To investigate the role of the NLRP3 inflammasome in MM, we determined
      the genetic polymorphisms and expression of NLRP3 inflammasome-related genes (IL
      1beta, IL-18, CARD8, and NF-kappaB) in MM patients, and explored their clinical
      relevance. Furthermore, we investigated the relationship of the NLRP3
      inflammasome with Th cells in MM. Our study showed that the CARD8-C10X
      (rs2043211) AT genotype contributed to the susceptibility of MM. CARD8-C10X TT
      patients had earlier clinical stage. The WBC count in the three CARD8 genotypes
      showed an increasing trend (AA<AT<TT). Compared with patients with NF-kappaB-94
      ins/del ATTG ins/ins and ins/del, patients with del/del had the highest myeloma
      cell ratio. Patients with IL-18 (rs16944) TT had the highest hemoglobin
      concentration (GG<GT<TT). Furthermore, we found that the genotype of CARD8-C10X
      (rs2043211) or NF-kappaB-94 ins/del ATTG was closely related to the frequency of
      Th1. Therefore, the genetic polymorphisms of the NLRP3 inflammasome associated
      with Th cells might be involved in the pathogenesis of multiple myeloma.

PMID- 30211236
TI  - Economic Evaluation of Using Pesticides to Control Cutaneous Leishmaniasis in
      Isfahan.
AB  - Objective: Pesticides have been used as the main part of the national cutaneous
      leishmaniasis control program for serveral years in Iran. However, the cost
      effectiveness of this strategy has not been yet analyzed. The aim of this study
      is to to analyze the cost-effectiveness and cost-utility of using pesticides as
      the main strategy to prevent rural CL in Isfahan. Methods: This is an economic
      evaluation study performed from a health system perspective to estimate the cost
      effectiveness and cost-utility of the control strategy with and without
      pesticides. The outcome measures are incidence rate of cutaneous leishmaniasis
      and the disability-adjusted life years (DALYs). The cost-effectiveness and cost
      utility have been analyzed by calculating incremental cost-effectiveness ratio
      (ICER). Data of cost and incidence rate obtained from the health centers of
      Isfahan University of Medical Sciences and Vice-Chancellery for Health. The
      disability weight was obtained from the literature. A one-way sensitivity
      analysis was applied with a 20% increase and decrease in costs. Findings: The
      total cost of control program in 2013 and 2014 were US$578,453 (ppp) and
      US$14,978.2 (ppp), respectively. The incidence rate of cutaneous leishmaniasis
      was estimated at 1396 and 1277 (per 100,000 population in hyperendemic areas
      where pesticides have been used) in 2013 and 2014, respectively. DALY lost due to
      disease was estimated to be 8.024 and 7.342 in 2013 and 2014, correspondingly.
      Both the cost-effectiveness and the cost-utility analyses resulted in negative
      ICERs, lying in the rejection area of the ICER plane. Conclusion: The use of
      pesticides to prevent cutaneous leishmaniasis (rural sicker) in Isfahan province
      has not proved to offer a reduction in the incidence rate of cutaneous
      leishmaniasis as well as reduction in DALYs lost. However, due to data
      availability limitation, the time frame for this study was limited. A prospective
      design with longitudinal data is recommended to be used by future research. Other
      alternatives to raise population awareness about different aspects of disease
      should be also considered for evaluation.

PMID- 30211232
TI  - Audiovestibular Symptoms in Systemic Autoimmune Diseases.
AB  - Immune-mediated inner ear disease can be primary, when the autoimmune response is
      against the inner ear, or secondary. The latter is characterized by the
      involvement of the ear in the presence of systemic autoimmune conditions.
      Sensorineural hearing loss is the most common audiovestibular symptom associated
      with systemic autoimmune diseases, although conductive hearing impairment may
      also be present. Hearing loss may present in a sudden, slowly, rapidly
      progressive or fluctuating form, and is mostly bilateral and asymmetric. Hearing
      loss shows a good response to corticosteroid therapy that may lead to near
      complete hearing restoration. Vestibular symptoms, tinnitus, and aural fullness
      can be found in patients with systemic autoimmune diseases; they often mimic
      primary inner ear disorders such as Meniere's disease and mainly affect both ears
      simultaneously. Awareness of inner ear involvement in systemic autoimmune
      diseases is essential for the good response shown to appropriate treatment.
      However, it is often misdiagnosed due to variable clinical presentation, limited
      knowledge, sparse evidence, and lack of specific diagnostic tests. The aim of
      this review is to analyse available evidence, often only reported in the form of
      case reports due to the rarity of some of these conditions, of the different
      clinical presentations of audiological and vestibular symptoms in systemic
      autoimmune diseases.

PMID- 30211234
TI  - Tributyrin Supplementation Protects Immune Responses and Vasculature and Reduces
      Oxidative Stress in the Proximal Colon of Mice Exposed to Chronic-Binge Ethanol
      Feeding.
AB  - Excessive ethanol consumption causes adverse effects and contributes to organ
      dysfunction. Ethanol metabolism triggers oxidative stress, altered immune
      function, and gut dysbiosis. The gut microbiome is known to contribute to the
      maintenance of intestinal homeostasis, and disturbances are associated with
      pathology. A consequence of gut dysbiosis is also alterations in its metabolic
      and fermentation byproducts. The gut microbiota ferments undigested dietary
      polysaccharides to yield short-chain fatty acids, predominantly acetate,
      propionate, and butyrate. Butyrate has many biological mechanisms of action
      including anti-inflammatory and immunoprotective effects, and its depletion is
      associated with intestinal injury. We previously showed that butyrate protects
      gut-liver injury during ethanol exposure. While the intestine is the largest
      immune organ in the body, little is known regarding the effects of ethanol on
      intestinal immune function. This work is aimed at investigating the effects of
      butyrate supplementation, in the form of the structured triglyceride tributyrin,
      on intestinal innate immune responses and oxidative stress following chronic
      binge ethanol exposure in mice. Our work suggests that tributyrin supplementation
      preserved immune responses and reduced oxidative stress in the proximal colon
      during chronic-binge ethanol exposure. Our results also indicate a possible
      involvement of tributyrin in maintaining the integrity of intestinal villi
      vasculature disrupted by chronic-binge ethanol exposure.

PMID- 30211237
TI  - Effect of Topical Chamomile Oil on Postoperative Bowel Activity after Cesarean
      Section: A Randomized Controlled Trial.
AB  - Objective: Postoperative ileus (POI) is a common complication after surgery that
      requires a multifactorial therapeutic approach. This study aims to assess the
      effect of topical chamomile oil on postoperative bowel activity after cesarian
      section. Methods: This randomized controlled trial was carried out in 2015 at
      Chamran Hospital in Iran. A block randomization list was generated for 142
      parturient divided into three groups. In the intervention group (arm A) (n = 47),
      chamomile oil was applied topically on abdominal region after the stability of
      the patient. Placebo group (arm B) (n = 47) received placebo oil and control
      group (arm C) (n = 48) had no intervention. A recovery program was used after
      surgery for all participants. The primary outcome was time to first flatus.
      Secondary outcomes were time to bowel sounds, defecation, return of appetite,
      hospital stay, and rate of nausea and vomiting, abdominal pain. Findings: Times
      to first flatus were significantly shorter in Group A (arm A vs. B, P < 0.001 and
      arm A vs. C, P < 0.001). In addition, time to first bowel sounds (arm A vs. B, P
      < 0.001 and arm A vs. C, P < 0.001) and return of appetite (arm A vs. B, P <
      0.001 and arm A vs. C, P < 0.001) were significantly shorter in arm A. The times
      from surgery to first defecation were shorter in Group A versus B and C. However,
      there were no statistically significant differences between three groups.
      Conclusion: These results suggest that topical chamomile oil has a potential
      therapeutic effect on gastrointestinal motility and can reduce the duration of
      POI.

PMID- 30211238
TI  - Anemia, Depression, and Suicidal Attempts in Women: Is There a Relationship?
AB  - Objective: Suicide is a social health problem worldwide. Anemia has been
      associated with depression. Since it remains debated whether anemia is associated
      with suicide independently of depression, we evaluate this probable association
      in women who attempted suicide through acute poisoning. Methods: The study design
      was cross-sectional and performed on women who attempted suicide through
      intentional poisoning with age more than 18 years old. Different variables were
      evaluated and compared in patients with respect to anemia, depression, other
      psychiatric diseases and history of suicide. Independent t-tests and binary
      logistic regression were used for statistical analysis. Findings: Nearly 26.2% of
      the women had anemia (n = 55). Most women with anemia were in the age group of 20
      40 years (68.8%). 52.2% of the women were married. Mixed-drug poisoning was the
      most common (60.1%) followed by pesticide (8.9%), and antipsychiatric medications
      (8.4%). There was a significant difference in duration of hospitalization between
      anemic and nonanemic patients. Nearly 72.7% of the patients survived without
      complications. Anemia and depression were not significant predictive factors for
      depression and suicide. However, in our patients, the presence of other
      underlaying psychiatric disorders was a risk factor for suicidal attempt through
      acute poisoning. Conclusion: In women who attempted suicide through acute
      poisoning, anemia and depression were not predicting factors for suicide.
      However, the presence of other underlying psychiatric psychiatric disorders had a
      predictive value for the outcome of treatment. Length of hospital stay was also
      correlated with anemia.

PMID- 30211240
TI  - Management of Febrile Neutropenia: A Description of Clinical and Microbiological
      Findings by Focusing on Risk Factors and Pitfalls.
AB  - Objective: Febrile neutropenia (FN) is one of the most serious clinical problems
      in patients with hematologic malignancies and patients receiving chemotherapy.
      The present study was implemented to determine precisely how FN is managed in
      most referral hospitals in Isfahan (Iran) and what are the characteristics of FN
      patients as well as risk factors associated with FN development. Methods: This
      study was a cross-sectional study performed over a period of 6 months on patients
      hospitalized in the Hematology-Oncology Center of Omid Hospital, Isfahan, Iran.
      The information was collected by filling the designed data abstraction form.
      Findings: A total of 115 oncology patients were admitted with or encountered to
      FN. This equates to a cumulative incidence of 1.26% of FN cases per 1000 oncology
      admissions. The average age was 49.5 +/- 18.02 years (range 18-85 years), with
      42.6% of patients being female. The most frequently prescribed antibiotic agents
      were meropenem (91.3%) and vancomycin (47.82%) alone or in combination. Empiric
      antifungal agents initiated in 20.86% of cases, and we could not find any
      patients who needed to receive antiviral treatment. From all positive cultures,
      Gram-positive microorganisms were the most found pathogen. Among them, female sex
      (42.6%) and lymphopenia (26.5%) were the most noted predictors. Neutropenia
      (81.7%) was the most reported risk factors for serious complications. Conclusion:
      Although our center is university-affiliated, there are still several points, and
      pitfalls must be considered and revised in the management of FN patients.
      Obtaining and assessing the samples microbiologically and antibiotic therapy
      accordingly were the most troublesome complications.

PMID- 30211239
TI  - Trial of Atorvastatin on Serum Interleukin-6, Total Antioxidant Capacity, C
      Reactive Protein, and Alpha-1 Antitrypsin in Patients with Chronic Obstructive
      Pulmonary Disease.
AB  - Objective: The present study was designed to investigate the effects of
      atorvastatin on serum high-sensitivity C-reactive protein (hs-CRP), interleukin-6
      (IL-6), total antioxidant capacity (TAC), and alpha-1 antitrypsin (AAT) in
      patients with chronic obstructive pulmonary disease (COPD). Methods: A clinical
      trial study conducted on 42 cases of COPD (Vali-Asr Hospital, Birjand, East of
      Iran, years 2014-16). Patients were randomly assigned to 21 controls and 21 cases
      who treated with atorvastatin (40 mg/day for 6 months). Inhaled corticosteroid
      and long-acting beta-agonist were administrated in both groups. The trial was
      registered at the Iranian Registry of Clinical Trials (registration number:
      IRCT2016042527594N1). TAC was measured by ferric reducing/antioxidant power
      assay. An enzyme-linked immunosorbent assay was used to determine IL-6, AAT, and
      hs-CRP. Spearman's rho test and Wilcoxon, Mann-Whitney, paired, and independent t
      tests were used for data analysis in SPSS 23. P < 0.05 was considered
      significant. Findings: A number of patients completed the study were 16 in
      atorvastatin and 18 in control group. Mean increments (MUmol/L) of TAC (mean +/-
      standard deviation [SD]) were 12.81 +/- 605.25 (P = 0.68) in atorvastatin and
      160.26 +/- 280.54 (P = 0.14) in control group. Mean decrements of IL-6, CRP, and
      AAT (mean +/- SD) were 1.41 +/- 5.51 (P = 0.71), 0.98 +/- 5.68 (P = 0.72), and
      10.94 +/- 46.83 (P = 0.21) in atorvastatin and 0.91 +/- 11.70 (P = 0.75), 3.23 +/
      7.00 (P = 0.19), and 18.77 +/- 55.90 (P = 0.21) in control group. Conclusion:
      Atorvastatin did not succeed in maintaining TAC and CRP reduction. However, less
      reduction in AAT and more reduction in IL-6 in the atorvastatin group would be
      likely a beneficial effect in COPD.

PMID- 30211241
TI  - Albumin Utilization Evaluation in a Major Teaching Hospital in Iran:
      Recommendations for Guideline Development.
AB  - Objective: Human albumin solution is an expensive colloidal preparation which is
      commonly used in clinical practice. Due to high cost of albumin, increased rate
      of the inappropriate use worldwide, and many other reasons, it is imperative to
      establish a practical protocol to use albumin products and limit its usage. The
      aim of this study was to identify albumin utilization patterns in a teaching
      hospital and to demonstrate the importance of the need to reconsider prescribing
      strategies for albumin administration. Methods: This retrospective cross
      sectional study was performed between August 2016 and December 2016 at Firoozgar
      Hospital affiliated to Iran University of Medical Sciences, Tehran, Iran. All
      albumin prescriptions for adult patients during the study period were enrolled
      for appropriateness evaluation according to the latest evidence-based studies and
      guidelines. Findings: Among 320 albumin prescriptions, 168 (52.5%) were
      inappropriate according to the current evidence. The most common irrational
      causes for the albumin usage were hypoalbuminemia (23.4%), nutritional support
      (13.7%), neuroprotection in subarachnoid hemorrhage (3%), pretreatment for cancer
      surgery (2.8%), edema (1.6%), hepatic failure (1.6%), and paracentesis (3%). The
      total amount of albumin used for 320 patients was 52,050 g, from which 28,470 g
      was inappropriate resulting in $97,398 wastage. Conclusion: These findings, along
      with aforementioned guidelines, support the requirement for physicians'
      educational programs and proper strategies for appropriate prescriptions and
      could also be important in modifying the available guidelines concerning
      expensive drugs such as albumin.

PMID- 30211242
TI  - Anterior Ischemic Optic Neuropathy in a Patient with Erectile Dysfunction:
      Tadalafil as an Offending Medication.
AB  - Erectile dysfunction (ED) has negative effects on quality of life. The first line
      of oral medication for this condition is phosphodiesterase type 5 inhibitors
      (PDE5I) including Tadalafil. Ocular complications associated with Tadalafil are
      rare and usually occurred in participant with known risk factors. In this report,
      we describe and review the related literature of development of nonarteritic
      anterior ischemic optic neuropathy -associated Tadalafil. A healthy nonsmoking 42
      year-old male with a history of ED presented with acute onset of an inferior
      visual field defect on the right eye. Automated perimetry showed inferior
      altitudinal loss in the affected eye. The administration of Tadalafil was
      discontinued as a potential causative agent for this condition. During follow-up,
      neither improvement signs nor symptoms revealed.

PMID- 30211243
TI  - A Newly Proposed Management Protocol for Acute Aluminum Phosphide Poisoning.

PMID- 30211244
TI  - An Unusual Cause of Acute Heart Failure: A Case Report of Iliocaval Venous Stent
      Migration.
AB  - Stent migration is an uncommon complication of endovascular stenting procedures.
      It could cause serious cardiovascular complications. In this article, we describe
      an interesting case of acute heart failure as a result of stent embolization from
      the left common iliac vein into the right ventricle and how it was identified and
      managed.

PMID- 30211245
TI  - Analysis of Publication Trends for the 2011-2015 American Orthopaedic Society for
      Sports Medicine Annual Meeting Abstracts.
AB  - Background: Academic conferences are sources of novel research that can influence
      clinical decision making. Orthopaedic surgery maintains a relatively high rate of
      publication compared with other surgical subspecialties, and sports medicine
      conferences hold an even higher rate within the subspecialty. The American
      Orthopaedic Society for Sports Medicine (AOSSM) annual meetings have been shown
      to have among the highest rates of publication for accepted abstracts. Purpose:
      To determine differences between 2-year publication rates of poster and podium
      abstracts accepted into the AOSSM annual meetings and identify factors associated
      with publication. Study Design: Cross-sectional study. Methods: The AOSSM
      archives were queried for all accepted poster and podium presentations for annual
      meetings from 2011 through 2015. Google Scholar and MEDLINE databases were used
      to determine which abstracts transitioned into journal articles. Publication
      rates were compared based on publication 2 years following presentation. Logistic
      regression was performed to demonstrate which variables were most correlated with
      successful publication. Data on publication impact factor and number of citations
      were collected by use of the InCites database. Results: Of 628 abstracts accepted
      during this period, 265 were poster presentations and 363 were podium
      presentations. Overall, 44.7% of abstracts presented were accepted into peer
      reviewed journals within 2 years of presentation. No statistical difference was
      found between poster and podium presentations for journal publication (P = .328).
      Poster presentations were published in journals with statistically lower impact
      factor (P = .005) and had a statistically lower number of citations (P < .001)
      compared with podium presentations. Multivariate logistic regression analysis
      demonstrated that only number of authors was correlated with publication (P =
      .003). Conclusion: Podium and poster presentations accepted into AOSSM
      conferences had equal rates of publication within 2 years and should influence
      decision making equally. The relative impact of podium presentations appeared to
      be greater, which suggests that the AOSSM selects podium presentations that will
      have greater clinical impact. Increasing number of coauthors was the only factor
      found to be correlated with publication.

PMID- 30211246
TI  - Risk Factors for Manipulation Under Anesthesia and/or Lysis of Adhesions After
      Anterior Cruciate Ligament Reconstruction.
AB  - Background: In the currently published literature, a higher risk for developing
      arthrofibrosis after anterior cruciate ligament (ACL) reconstruction has been
      reported for female patients, adolescents, early surgery or concomitant
      procedures, and the use of a patellar tendon autograft. There is a lack of
      evidence regarding other graft choices or factors. Hypothesis: Multiple risk
      factors will play a significant role in the development of arthrofibrosis after
      ACL reconstruction. Specifically, we hypothesized that the risk of manipulation
      under anesthesia (MUA) and/or lysis of adhesions (LOA) would be affected by graft
      choice and patient demographic factors. Study Design: Case-control study; Level
      of evidence, 3. Methods: The charts of all patients who underwent ACL
      reconstruction over a 10-year period at a single academic institution were
      queried from an electronic medical record database and reviewed at a minimum of 6
      months after ACL reconstruction, with the collection of demographic and surgical
      data. The relative risk for undergoing MUA and/or LOA was calculated for each
      analyzed risk factor. Results: A total of 2424 ACL reconstructions were included,
      with a chart review at a mean of 56.7 months after surgery (range, 7.6-124.0
      months). The rate of MUA and/or LOA for arthrofibrosis was 4.5%. A statistically
      significantly increased relative risk was found for infection (5.45), hematoma
      requiring evacuation (3.55), ACL reconstruction with meniscal repair (2.83), use
      of a quadriceps tendon autograft (2.68), age <18 years (2.39), multiple
      concomitant procedures (1.69), contact injury (1.62), female sex (1.60), and
      surgery within 28 days of injury (1.53), and a statistically significantly
      decreased relative risk was found for revision ACL reconstruction (0.30), age >25
      years (0.34), and use of a tibialis anterior allograft (0.36). In the
      multivariate regression model, the use of a quadriceps tendon autograft (P =
      .00007), infection (P = .00126), and concomitant meniscal repair (P = .00194)
      were independent risk factors, whereas revision ACL reconstruction (P = .0024)
      was an independent protective factor. Conclusion: Graft type, infection,
      concomitant meniscal repair, and primary reconstruction are significant risk
      factors for undergoing MUA or LOA after ACL reconstruction.

PMID- 30211247
TI  - Outpatient Parenteral Antimicrobial Therapy Among People Who Inject Drugs: A
      Review of the Literature.
AB  - Hospitalizations for people who inject drugs (PWID) with infectious complications
      requiring prolonged antibiotic therapy are increasing in the context of the
      opioid epidemic. Although outpatient parenteral antimicrobial therapy (OPAT) is
      routinely offered to patients without a history of injection drug use (IDU), PWID
      are often excluded from consideration of OPAT. To better assess the evidence base
      for the safety and effectiveness of OPAT for PWID, we conducted a review of the
      published literature. Results suggest that OPAT may be safe and effective for
      PWID, with rates of OPAT completion, mortality, and catheter-related
      complications comparable to rates among patients without a history of IDU. Rates
      of hospital readmissions may be higher among PWID, but instances of misuse of the
      venous catheter were rarely reported. More research is needed to study the safety
      and effectiveness of OPAT among PWID, as well as studying the combination of OPAT
      and addiction treatment.

PMID- 30211248
TI  - Low Case Finding Among Men and Poor Viral Load Suppression Among Adolescents Are
      Impeding Namibia's Ability to Achieve UNAIDS 90-90-90 Targets.
AB  - Background: In 2015, Namibia implemented an Acceleration Plan to address the high
      burden of HIV (13.0% adult prevalence and 216 311 people living with HIV [PLHIV])
      and achieve the UNAIDS 90-90-90 targets by 2020. We provide an update on
      Namibia's overall progress toward achieving these targets and estimate the
      percent reduction in HIV incidence since 2010. Methods: Data sources include the
      2013 Namibia Demographic and Health Survey (2013 NDHS), the national electronic
      patient monitoring system, and laboratory data from the Namibian Institute of
      Pathology. These sources were used to estimate (1) the percentage of PLHIV who
      know their HIV status, (2) the percentage of PLHIV on antiretroviral therapy
      (ART), (3) the percentage of patients on ART with suppressed viral loads, and (4)
      the percent reduction in HIV incidence. Results: In the 2013 NDHS, knowledge of
      HIV status was higher among HIV-positive women 91.8% (95% confidence interval
      [CI], 89.4%-93.7%) than HIV-positive men 82.5% (95% CI, 78.1%-86.1%). At the end
      of 2016, an estimated 88.3% (95% CI, 86.3%-90.1%) of PLHIV knew their status, and
      165 939 (76.7%) PLHIV were active on ART. The viral load suppression rate among
      those on ART was 87%, and it was highest among >=20-year-olds (90%) and lowest
      among 15-19-year-olds (68%). HIV incidence has declined by 21% since 2010.
      Conclusions: With 76.7% of PLHIV on ART and 87% of those on ART virally
      suppressed, Namibia is on track to achieve UNAIDS 90-90-90 targets by 2020.
      Innovative strategies are needed to improve HIV case identification among men and
      adherence to ART among youth.

PMID- 30211251
TI  - Population-based study of "no evident disease activity" in MS.
AB  - Objective: To determine the persistence of no evident disease activity (NEDA) in
      a population-based relapsing-remitting MS (RRMS) cohort. Methods: All incident
      cases of RRMS in Olmsted County between 2000 and 2011 were identified using a
      medical records linkage system. Persistence of NEDA after RRMS diagnosis was
      determined by retrospective chart review. MRI activity, relapse, or Expanded
      Disability Status Scale (EDSS) worsening resulted in failure of NEDA. Results: We
      identified 93 incident cases of RRMS including 82 individuals with sufficient
      follow-up to determine the persistence of NEDA. There were 44 individuals not on
      disease-modifying therapy (DMT), whereas 37 individuals were prescribed an
      injectable DMT and 1 received mitoxantrone during the interval over which NEDA
      was maintained. NEDA was maintained by 63% at 1 year, 38% at 2 years, 19% at 5
      years, and 12% at 10 years according to routine care assessment. At 10 years,
      there was no difference in EDSS disability among patients who maintained NEDA vs
      those who failed NEDA at 1 year (p = 0.3). Conclusions: NEDA infrequently
      persists beyond 2 years in a population-based cohort of newly diagnosed patients
      with RRMS.

PMID- 30211249
TI  - Screening Clinical Cell Products for Replication Competent Retrovirus: The
      National Gene Vector Biorepository Experience.
AB  - Replication-competent retrovirus (RCR) is a safety concern for individuals
      treated with retroviral gene therapy. RCR detection assays are used to detect RCR
      in manufactured vector, transduced cell products infused into research subjects,
      and in the research subjects after treatment. In this study, we reviewed 286
      control (n = 4) and transduced cell products (n = 282) screened for RCR in the
      National Gene Vector Biorepository. The transduced cell samples were submitted
      from 14 clinical trials. All vector products were previously shown to be negative
      for RCR prior to use in cell transduction. After transduction, all 282 transduced
      cell products were negative for RCR. In addition, 241 of the clinical trial
      participants were also screened for RCR by analyzing peripheral blood at least 1
      month after infusion, all of which were also negative for evidence of RCR
      infection. The majority of vector products used in the clinical trials were
      generated in the PG13 packaging cell line. The findings suggest that screening of
      the retroviral vector product generated in PG13 cell line may be sufficient and
      that further screening of transduced cells does not provide added value.

PMID- 30211252
TI  - Physical activity and dentate gyrus volume in pediatric acquired demyelinating
      syndromes.
AB  - Objective: To assess the association between daily moderate-to-vigorous physical
      activity (MVPA) and dentate gyrus volume (DGv) in pediatric patients with
      acquired demyelinating syndromes (ADSs) of the CNS. Methods: Cross-sectional
      analysis of accelerometry (7 days) and research protocol MRI data from 12
      pediatric MS and 18 children with monophasic ADS (monoADS). Total brain and DGv
      were quantified using standardized methods. The association of daily minutes of
      MVPA with normalized DGv (nDGv) was assessed using multivariable generalized
      linear models. Results: Median (interquartile range) MVPA was lower in MS
      patients [9.5 (14)] and exhibited less variation than in monoADS patients [24.5
      (47)]. nDGv did not differ significantly between groups [mean nDGv (SD) [cm3]: MS
      0.34 (0.1); monoADS 0.4 (0.1); p = 0.100]. In the monoADS group, every 1-minute
      increase in MVPA was associated with a 2.4-mm3 increase in nDGv (p = 0.0017), an
      association that was independent of age at incident demyelination, time from
      incident demyelination, sex, and brain white matter T2 lesion volume. No
      significant association was found between MVPA and nDGv (-2.6 mm3/min, p = 0.16)
      in the MS group. Conclusions: Higher MVPA associates with greater nDGv in
      children who have recovered from monophasic demyelination. Larger studies are
      required to determine whether MVPA can promote regional brain development, or
      limit tissue damage, in youth with MS.

PMID- 30211253
TI  - Varicella-zoster virus CNS vasculitis and RNA polymerase III gene mutation in
      identical twins.
AB  - Objective: Deficiency in the cytosolic DNA sensor RNA Polymerase III (POL III)
      was recently described in children with severe varicella-zoster virus (VZV)
      infection in the CNS or lungs. Here, we describe a pair of monozygotic female
      twins, who both experienced severe recurrent CNS vasculitis caused by VZV
      reactivation. The clinical presentation and findings included recurrent episodes
      of headache, dizziness, and neurologic deficits, CSF with pleocytosis and
      intrathecal VZV antibody production, and MRI of the brain showing ischemic
      lesions. Methods: We performed whole-exome sequencing and identified a rare
      mutation in the POL III subunit POLR3F. Subsequently, antiviral responses in
      patient peripheral blood mononuclear cells (PBMCs) were examined and compared
      with healthy controls. Results: The identified R50W POLR3F mutation is predicted
      by bioinformatics to be damaging, and when tested in functional assays, patient
      PBMCs exhibited impaired antiviral and inflammatory responses to the POL III
      agonist poly(dA:dT) and increased viral replication compared with controls.
      Conclusions: Altogether, these cases add genetic and immunologic evidence to the
      novel association between defects in sensing of AT-rich DNA present in the VZV
      genome and increased susceptibility to severe manifestations of VZV infection in
      the CNS in humans.

PMID- 30211254
TI  - Filter tilting and retrievability of the Celect and Denali inferior vena cava
      filters using propensity score-matching analysis.
AB  - Purpose: To assess the filter tilting and outcomes of the Celect and Denali
      inferior vena cava (IVC) filters by using a propensity score-matching analysis.
      Materials and methods: From January 2009 to November 2017, 181 Celect and 58
      Denali filters were inserted in our institution. To assess filter tilt, filter
      tip abutment or penetration of the IVC wall, and retrieval outcome, independent
      variables, including age, sex, IVC long diameter, IVC angulation, and proximity
      of the filter to renal vein insertion, were entered in the propensity model.
      Comparative analyses were performed before and after propensity score-matching
      analysis. Results: Thirty-one patients were enrolled in each group for the final
      propensity score-matching analysis. The mean filter indwelling time was not
      significantly different between the groups (26 +/- 22 days in Celect and 27 +/-
      23 days in Denali). After propensity score adjustment, the mean degree of filter
      tilt was higher in the Celect group (9.5 degrees  +/- 7.4 degrees  vs 5.6 degrees
      +/- 6.7 degrees ). Filter tip abutment or penetration of the IVC wall was more
      common in the Celect group (39% [12/31, abutment: 12, penetration: 0] vs 13%
      [4/31, abutment: 3, penetration: 1]). The retrieval outcomes were not
      significantly different before and after propensity score adjustment in both
      filters. Conclusion: The Denali IVC filter showed less tilt and low rate of
      filter tip abutment to the IVC wall after propensity score-matching analysis. The
      retrieval rate was not significantly different in the short-term filter
      indwelling setting. More large-scale, long-term follow-up studies are needed to
      verify these results.

PMID- 30211250
TI  - Atypical neural modulation in the right prefrontal cortex during an inhibitory
      task with eye gaze in autism spectrum disorder as revealed by functional near
      infrared spectroscopy.
AB  - Autism spectrum disorder (ASD) is characterized by impairment in social
      communication and the presence of restricted and repetitive behaviors and
      interests. Executive function impairment is reportedly partially responsible for
      these symptoms. Executive function includes planning, flexibility, and inhibitory
      control. Although planning and flexibility in ASD have been consistently reported
      as atypical, the atypicality of inhibitory control remains controversial. As most
      previous studies have used nonsocial stimuli to investigate inhibitory control in
      ASD, the effects of socially relevant information on the inhibitory control
      system in individuals with ASD remain unclear. Therefore, we developed a go/no-go
      task with gaze stimuli and measured hemodynamic responses in the right prefrontal
      cortex (PFC), involved in inhibitory processing in both typically developing (TD)
      children and children with ASD, using functional near-infrared spectroscopy.
      Direct gaze induced commission errors to similar extents in both groups. Contrary
      to the behavioral responses, neural activation in the right PFC was modulated by
      gaze direction only in the TD group. These findings suggest that the gaze
      processing mechanisms in the prefrontal region may be affected by atypical gaze
      processing in other brain regions during an inhibitory control task with socially
      relevant information in ASD.

PMID- 30211255
TI  - Dataset demonstrating physical properties of recycled wind turbine blade
      composites.
AB  - Wind turbine blades that face end-of-life recycled mechanically. The recycled
      material was first comminuted via a hammer-mill through a range of varying screen
      sizes, resinated and compressed to a final thickness to manufacture second
      generation composites fabricated using recycled wind turbine material and a
      polyurethane adhesive. Physical properties (water sorption (WA), Thickness
      swelling (TS)) dataset of composites made from recycled wind turbine blades
      presented. Dataset also presented the influence of resin level, moisture content,
      mill screen size and density on the physical properties of composites.

PMID- 30211256
TI  - A bibliographic database on economic analysis of natural forest disturbances.
AB  - The data presented here are related to the research paper entitled "Economic
      Analysis of Natural Forest Disturbances: A Century of Research" (Montagne-Huck
      and Brunette, 2018). Natural disturbances have always affected forest ecosystems,
      altering or disrupting the flows of goods (wood, non-timber products, etc.) and
      services (scenic and recreation values, leisure pursuits, clean water, regulation
      of floods, etc.) provided by forests to human societies. Economic analysis can
      help private or public decision-makers take forest policy decisions by
      understanding the causes and consequences of forest disturbances, as well as
      evaluating tradeoffs in alternative policy scenarios. In consequence, the
      economic literature about natural disturbances is very rich and diversified. This
      paper describes a bibliographic database gathering some 340 scientific papers
      related to the economic analysis of forest natural disturbances. Papers have been
      inventoried primarily thanks to searches on databases (JSTOR, ScienceDirect,
      Ingentaconnect and NRC Research Press) using specific keywords and the dataset
      have been completed by searching through literature-cited sections of papers.
      Relevant papers have been manually encoded into a database (Excel file) taking
      into consideration each type of hazard (storm, fire, snow, pests and diseases,
      etc.) and different economic approaches. Data cover papers published in English
      from 1916 to 2014.

PMID- 30211257
TI  - Data set on the antibacterial effects of the hydro-alcoholic extract of Ferula
      assafoetida plant on Listeria monocytogenes.
AB  - The aim of the collection of the present dataset is to show the antibacterial
      effects of the hydro-alcoholic extract of Ferula assafoetida plant on Listeria
      monocytogenes. Firstly, the Ferula assafoetida herb was collected from
      investigated hills in Gonabad, Khorasan province, Iran. After botanical and
      pharmocognosy investigation, the hydro-alcoholic extract of this herb was
      produced using percolation method. Then, its antimicrobial effects, Minimum
      Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC), were
      investigated using Disc Diffusion Method and Macro Dilution Method vs. Listeria
      Monocytogenes, serotypes 4a and 4b, respectively. Also, Ampicillin (10 ug/disc)
      was used as a reference antimicrobial material. The data showed that MIC and MBC
      of the Ferula assafoetida extract on Listeria monocytogenes was 7.25 ug/ml and
      12.50 ug/ml, respectively. Moreover, the average diameter of the inhibitory zone
      of extracted hydrolcoholic from Ferula Alliacea plant over Listeria monocytogenes
      4a and 4b (30 g/ml) were 16.35 2.5 and 15.87 3.1 mm, respectively, and in order
      for ampicillin was 24.31 2.45 and 24.31 2.45 mm. The hydro-alcoholic extract
      produced from Ferula assafoetida can be used as the antibacterial for Listeria
      Monocytogenes.

PMID- 30211258
TI  - Experimental data on the mechanical properties of individual caobilla wood cubes
      used on control pile systems.
AB  - This article contains data on the mechanical properties of individual cubes of
      caobilla wood (Swietenia humilis Zucc.) used as deformable cell of control piles,
      which are a special foundation system used to regulate both loads and settlements
      in buildings. The data were obtained from stress-controlled compression tests
      considering wooden cubes with different volumetric weight, moisture conditions
      and fiber orientation. In addition, the correlation of yield stress versus
      volumetric weight of caobilla wood cubes is presented. The mean values and
      standard deviations of volumetric weight and yield stress of the tested wooden
      cubes under dry and wet states are also presented.

PMID- 30211259
TI  - Systemic neutrophil migration and rapid consumption of neutrophils in the spleen.
AB  - The systemic migration of neutrophils is not fully understood. In this study, we
      purified neutrophils from rat peripheral blood and labeled them with [51Cr]
      sodium chromate. The labeled cells were injected into the tail veins of rats, and
      were traced. Neutrophils were rapidly trapped in the liver and the spleen within
      6 h. The migration ratios of neutrophils in the lung and the gut were lower
      compared with those in the liver and the spleen. Interestingly, migrated cells
      into the spleen were rapidly phagocytosed by monocytes/macrophages. Therefore,
      accumulation of intact neutrophils in the spleen may be difficult to measure.

PMID- 30211260
TI  - Intra-annual raw basal area increments (early-wood and late-wood) of Pinus nigra
      subsp. laricio Poiret trees from southern Italy at the pines' mesic to xeric
      distribution range.
AB  - This article contains tree rings data related to the research article entitled
      "An intra-stand approach to identify intra-annual growth responses to climate in
      Pinus nigra subsp. laricio Poiret trees from southern Italy" (Mazza et al.,
      2018). Most dendroclimatological studies on black pine have been conducted on the
      P. nigra subsp. nigra, while only few results on climate-growth relationships are
      available for other taxa such as P. nigra subsp. laricio, which has the narrowest
      distribution range of the collective species P. nigra. This data article provides
      tree rings data for the subsp. laricio at an intra-annual growth level,
      distinguishing early-wood (EW) and late-wood (LW), from an even aged forest stand
      from the Sila mountain area within the subspecies mesic to xeric distribution
      range.

PMID- 30211261
TI  - Data to model risks for recolonizing wolves in Scandinavia through the
      integration of territory presence and human-driven mortalities.
AB  - This dataset article describes the data and sources used to model risks for the
      recolonizing wolf (Canis lupus) in Sweden and Norway in the article "Integrated
      spatially-explicit models predict pervasive risks to recolonizing wolves in
      Scandinavia from human-driven mortality" (Recio et al., 2018). Presences on wolf
      territories were used to model the potential distribution of the species.
      Presences of human-driven mortalities including traffic collisions, culling
      (protective/defensive, and licensed hunting), and illegal killing (i.e. poaching)
      were used to model predictions on the distribution of these mortalities. Sources
      for the independent variables used for the models are also described.

PMID- 30211262
TI  - Data on association of ankle pressure and ankle brachial index of symptomatic and
      contralateral lower extremities with overall and cardiovascular mortality in
      patients with lower extremity peripheral artery disease.
AB  - Data on survival curves for overall survival and freedom from cardiovascular
      death at different ankle brachial index (ABI) and ankle pressure (AP) are shown
      separately for symptomatic and contralateral lower limbs in 721 patients with
      lower extremity peripheral artery disease at up to 7 years follow-up. Cox
      regression analysis with confounding factors for ABI and AP are also shown. Dates
      and causes of death were collected from the Finnish national statistics registry.

PMID- 30211263
TI  - Influence of talent retention strategy on employees' attitude to work: Analysis
      of survey data.
AB  - In this data article, an analysis on the strategies for talent retention in
      Covenant University and the corresponding effects on employees' attitude to work
      was presented. The study population included the academic staff of Covenant
      University, which has a population of 530 employees, but a sample size was
      determined using Yamen's formula. The data obtained through survey questionnaires
      were analysed using Statistical Package for Social Sciences (SPSS). Linear
      regression was used to model the effect of talent retention strategy on
      employees' attitude to work. This information is made publicly available to aid
      empirical researches on the subject of talent management in organizations.

PMID- 30211264
TI  - Dataset on aerosol loading, size and statistics over Sanpedro.
AB  - Dataset on the aerosol loading and aerosol size radius was provided to guide
      researcher on the health implication of the air pollution over the research area.
      Fifteen years primary (aerosol optical depth) dataset was obtained from the Multi
      angle Imaging Spectro-Radiometer (MISR). Aerosol loading were generated from the
      primary dataset. The dataset is important the major cause of respiratory diseases
      recorded in Sanpedro-Cote d'Ivoire.

PMID- 30211265
TI  - The dataset on rural women's awareness and attitudes about residential
      constructions in accordance with the health standards A case study of Gilan-e
      Gharb, Iran.
AB  - Residence can affect various aspects of one's physical, psychological and social
      health. Therefore, the present dataset aimed to assess the level of rural
      housewives' awareness and attitudes towards the importance of residence and its
      compliance with health standards. To collect the present dataset, four villages
      were selected from the Gilan-e-Gharb township using the randomized cluster
      sampling method, then 25 subjects were chosen from each village (totaling 100
      altogether). Furthermore, the subjects' awareness and attitudes were measured
      using a researcher-made questionnaire, and the data were then analyzed using the
      SPSS Statistical Software Version 21.0. The obtained data demonstrated that rural
      housewives' awareness and attitudes towards the subject were significantly
      different in terms of education and age group (P< 0.05), but the opposite was
      true in terms of the variables of marital status and training by health
      practitioners (P> 0.05). Based on the obtained data, the awareness and attitudes
      of rural women towards the importance and necessity of health standards of
      residence were low and moderate, respectively. In addition, providing rural women
      with effective training in various ways to raise their awareness and attitudes is
      of prime significance.

PMID- 30211266
TI  - Proteome data of Anopheles stephensi ovary using high-resolution mass
      spectrometry.
AB  - This article contains data on the proteins expressed in the ovaries of Anopheles
      stephensi, a major vector of malaria in India. Data acquisition was performed
      using a high-resolution Orbitrap-Velos mass spectrometer. The acquired MS/MS data
      was searched against An. stephensi protein database comprising of 11,789
      sequences. Overall, 4407 proteins were identified, functional analysis was
      performed for the identified proteins and a protein-protein interaction map
      predicted. The data provided here is also related to a published article -
      "Integrating transcriptomics and proteomics data for accurate assembly and
      annotation of genomes" (Prasad et al., 2017) [1].

PMID- 30211267
TI  - Original dataset used in the article "Does Pokemon Go lead to a more physically
      active life style?"
AB  - The data presented in this article are related to the research article entitled
      "Does Pokemon Go lead to a more physically active life style?" (Gabbiadini et
      al., in press) [1]. In the study, 981 individuals completed a web survey, in
      which frequency of Pokemon Go usage, overall physically active behavior, and
      amount of Pokemon Go related physical activity were measured. Regression analyses
      revealed that Pokemon Go related physical activity significantly reversed the
      positive effects of the app on participants' overall physically active behavior,
      suggesting that the mere adoption of the app does not reliably change people's
      behavior in general. The increase in physical activity levels is rather explained
      by the exercise required by the game. The data set is made publicly available to
      enable critical or extended analyzes.

PMID- 30211268
TI  - Passive noise datasets at regolith sites.
AB  - The data presented in this article contain datasets of passive noise measurements
      at regolith sites in Adelaide, South Australia. The data were acquired using
      three component (3C) LE-3Dlite Lennartz seismometers with an eigenfrequency of 1
      Hz. The data were acquired at eight sites across Adelaide's regolith in a
      hexagonal array layout. Four tests, each with a duration of 30 min, were
      conducted at different times. The ambient noise data can be used for both
      horizontal to vertical spectral ratio (HVSR) analysis and array analyses, which
      are essential to obtain the site fundamental frequency and the ellipticity of the
      fundamental mode Rayleigh waves at the measured site. The array analyses are
      useful to obtain the dispersion curves, which are needed to estimate the shear
      wave velocity profile.

PMID- 30211269
TI  - A long-term 0.01 degrees  surface air temperature dataset of Tibetan Plateau.
AB  - The surface air temperature (Ta) dataset of the Tibetan Plateau is obtained by
      downscaling the China regional surface meteorological feature dataset (CRSMFD).
      It contains the daily mean Ta and 3-hourly instantaneous Ta. This dataset has a
      spatial resolution of 0.01 degrees . Its time range for surface air temperature
      dataset is from 2000 to 2015. Spatial dimension of data: 73 degrees E-106 degrees
      E, 40 degrees N-23 degrees N. The Ta with a 0.01 degrees  can serve as an
      important input for the modeling of land surface processes, such as surface
      evapotranspiration estimation, agricultural monitoring, and climate change
      analysis.

PMID- 30211271
TI  - ISSR diversity in Jatropha curcas germplasm and offspring of selected parentals.
AB  - This article contains metadata related to the research article "Behavior of
      genetic diversity in F1 crosses of selected accessions of Jatropha curcas"
      (Sanchez-Velazquez et al., 2018). The data presented in this article belong to a
      diversity study using ISSR molecular markers of a J. curcas germplasm collection
      that includes bred offspring and analysis of similarity between accessions. We
      tested previously reported primers in PCR assays to obtain a genetic profile of
      the accessions. These profiles were used to calculate Dice similarities.
      Similarity between offspring and parentals can be compared either with the
      maternal side or paternal side.

PMID- 30211270
TI  - Data for serum 1,5 anhydroglucitol concentration in different populations.
AB  - 1,5 anhydroglucitol (1,5-AG), is a nonmetabolized 1-deoxy form of glucose,
      originate mainly from the diet. 1,5-AG is a biomarker to detect and magnify
      hyperglycemic excursions (postprandial hyperglycemia) in diabetic patients.
      Concentrations of 1,5-AG has been applied as supporting biomarker to diagnosis of
      the major forms of diabetes (type 1, type 2, and gestational). The serum 1,5-AG
      reference interval is relevant to the appropriate clinical application of this
      biomarker. This article contains data regards to serum concentration of the
      biomarker primarily for healthy subjects, capture from the literature, in
      different populations. Correlation analysis between 1,5-AG and markers associated
      with diabetes and its complication were presented. The data was complementary to
      the study "Reference intervals for serum 1,5-anhydroglucitol in children,
      adolescents, adults, and pregnant women" (Welter et al., 2018). The data present
      in this article improve the comparisons for 1,5-AG in different conditions and
      methodologies.

PMID- 30211272
TI  - Tobacco tax and price in the developed and developing countries in the World.
AB  - An ecologic study was conducted on 177 countries which the information of tobacco
      tax and price and also Human Development Index (HDI) was available in 2014. In
      this study, the relationship between HDI and four reported indexes by World
      Health Organization (WHO) was studied. These four indexes included: Tobacco
      affordability, Taxes as a percent of price of the most sold brand (total tax),
      Price of a 20 cigarette pack of the most sold brand international dollars at
      purchasing power parity (Price_ppp) and Price of a 20 cigarette pack of the most
      sold brand in US$ at official exchange rates (Price_US$). The data of HDI and
      tobacco were mined from WHO and United Nations Development Programme sites
      respectively. To study the correlation between HDI and the variables of this
      study, Pearson correlation coefficient was used and also Linear Regression
      Analysis was used to study the relationship between HDI and the variables of the
      study. According to the findings of the linear regression analysis, there was a
      significant relationship between HDI and total tax (B = 0.81, CI 95%: 0.63-0.99)
      and tobacco affordability (B = --0.35, CI 95%: --0.42 _ --0.28). There was also a
      significant relationship between HDI whit price-ppp (B = 9.44, CI 95%: 7.13
      11.75) and price-US$ ;(B = 11.97, CI 95%: 9.71-14.23). According to the findings
      of this study, less developed countries devote less tax on tobacco. Due to the
      rising trend of the prevalence and also development of non-communicable diseases
      such as lung cancer in developing countries, policy makers of these countries are
      required to design stricter policies toward tobacco production and supply as
      well.

PMID- 30211273
TI  - Survey data on bureaucratic processes and entrepreneurial venture performance in
      SMEs in Nigeria.
AB  - This article presents data that examined the impact of bureaucratic processes on
      the performance of small and medium enterprises in Nigeria. A survey was carried
      out by administering the questionnaire to 400 business owners selected from three
      reputable associations, namely: NASME, NASSI and ASBON (Nigerian Association of
      Small and Medium Enterprises, National Association of Small Scale Industrialists
      and Association of Small Business Owners of Nigeria) in three geo-political
      zones. Data were analysed using Predictive Analytics Software. Correlation and
      Regression were employed as inferential statistical tool of analysis. Data set
      revealed the existence of relationship and the extent to which bureaucratic
      processes impact the performance of entrepreneurial ventures.

PMID- 30211275
TI  - Data on nephroprotective effect of all-trans retinoic acid in early diabetic
      nephropathy.
AB  - Data showed in this report are related to the research article entitled "All
      trans retinoic acid ameliorates inflammatory response mediated by TLR4/NF-kB
      during the initiation of diabetic nephropathy" by Sierra-Mondragon et al. (2018)
      [1]. Diabetic nephropathy (DN) has become the main cause of renal failure.
      Inflammatory molecules such as cytokines, chemokines and growth factors play a
      key role in DN-induced renal injury Pichler et al. (2016) [2]. Results illustrate
      the effect of all-trans retinoic acid (ATRA), an active metabolite of vitamin A,
      on the renal alterations related to diabetes, among them glomerular and tubular
      dysfunction, and its effect on renal inflammation in different nephron segments:
      glomeruli, proximal and distal tubules in an initial stage of DN. Data were
      obtained by physical-biochemical measurements and Western blot assays performed
      on isolated glomeruli, proximal and distal tubules from rat kidneys.

PMID- 30211274
TI  - Data for Tandem Mass Tag (TMT) proteomic analysis of the pancreas during the
      early phase of experimental pancreatitis.
AB  - The quantitative proteomics data reported here pertain to the research article
      entitled "A Tandem Mass Tag (TMT) proteomic analysis during the early phase of
      experimental pancreatitis reveals new insights in the disease pathogenesis"
      (Garcia-Hernandez et al., 2018) [1]. The development of acute pancreatitis (AP,
      an important pathological inflammatory state of the exocrine pancreas) would be
      based on early changes in protein expression and signaling pathways whose
      unmasking would be crucial for deciphering AP at the molecular level. We reported
      here a Tandem Mass Tag (TMT)-based proteomics analysis of rat subcellular
      fractions of the pancreas during the early phase of experimental AP, using a
      sixplex isobaric chemical labeling technique. We identified 997 unique proteins,
      of which 353 were significantly different (22, 276 or 55 in both, the soluble or
      the membrane fractions, respectively). Accordingly, using TMT proteomics and
      bioinformatic tools, in Garcia-Hernandez et al., 2018- [1] we were able to detect
      significant changes in protein expression related to many pathobiological
      pathways of AP as from the early phase of the disease, including some changes
      never described before in this disease. Proteomics data are publicly available in
      ProteomeXchange via PRIDE through the identifier PXD007096.

PMID- 30211276
TI  - Dataset analysis on Cu9S5 material structure and its electrochemical behavior as
      anode for sodium-ion batteries.
AB  - The data presented in this data article are related to the research article
      entitled "Facile Synthetic Strategy to Uniform Cu9S5 Embedded into Carbon: A
      Novel Anode for Sodium-Ion Batteries" (Jing et al., 2018) [1]. The related
      experiment details of pure Cu9S5 has been stated. The structure data of pure
      Cu9S5 and the electrochemical performance for sodium-ion batteries are described.

PMID- 30211277
TI  - European Central Bank's monetary policy decisions: A dataset of two decades of
      press conferences.
AB  - The dataset gathers all press conferences in text form made by the first three
      Presidents of the European Central Bank since its inception in 1998. Press
      conferences are composed of two elements: (1) introductory statements and (2)
      questions and answers (Q&A) from journalists. They serve as the main
      communication vehicle about the monetary policy decision of the ECB's Governing
      Council. From 1998 to 2016, a total of 205 press conferences have been delivered.
      The dataset is structured into two main sections: (1) 205 introductory statement
      of the Presidents of the ECB explaining the monetary policy of the Institution
      and (2) 205 answers provided by the Presidents to the journalists, hence a total
      of 410 statements (914,499 words or 3050 pages) about the monetary policy and its
      context, in text form.

PMID- 30211278
TI  - Data on the fluoride adsorption from aqueous solutions by metal-organic
      frameworks (ZIF-8 and Uio-66).
AB  - The variables examined were initial fluoride concentration, ZIF-8 and Uio-66
      dosage, pH, and contact time. The residual concentration of fluoride was measured
      by a spectrophotometer. According to BET, the specific surface area of the ZIF-8
      and Uio-66 was 1050 m2/g and 800 m2/g, respectively. Total pore volume and
      average pore diameter of the ZIF-8 and Uio-66 were 0.57 cm3/g, 0.45 cm3/g and 4.5
      nm, 3.2 nm, respectively. The best pH for fluoride adsorption was neutral
      conditions. By increasing the ZIF-8 and Uio-66 dose, the fluoride uptake
      increased at first, but then decreased. Also, the maximum adsorption for ZIF-8
      and Uio-66 was observed in adsorbent dose 0.2 and 0.6 g/L, respectively. The best
      model for describing kinetic and isotherms of fluoride adsorption were the pseudo
      second-order model and Langmuir isotherm model, respectively. Based on the
      Langmuir model, the adsorption capacity of fluoride by ZIF-8 and Uio-66 was
      reported to be 25 mg/g and 20 mg/g, respectively.

PMID- 30211279
TI  - Construction, expression, and characterization of AG11-843 and AG11-1581.
AB  - This data article contains descriptive and experimental data on the construction,
      expression, and simple characterization of AG11-843 and AG11-1581. AG1 is an
      important member of the DUF1220 protein family. It's hard to get the recombinant
      protein because of its DNA sequence. The DNA sequence were optimized by proper
      design, cloned by overlap PCR and constructed into expression vector. AG11-843
      and AG11-1581.were over expressed in Escherichia coli, purified and analyzed by
      dynamic light scattering and gel filtration analysis. An effective technique is
      provided to construct and express proteins with complicated sequences.

PMID- 30211280
TI  - Dataset on sustainable construction practices of foreign and indigenous
      construction firms.
AB  - This dataset conducted a comparative analysis of sustainable construction
      practices of foreign and indigenous construction firms in Lagos state, Nigeria
      using a structured questionnaire survey. The dataset contains the level of
      awareness and consistency of practice of sustainable development on construction
      projects between the foreign and indigenous construction firms and the impact of
      implementing sustainable development practices. Descriptive analysis such as
      frequencies, percentage and mean score were used to present the quantitative data
      in form of tables. Further analysis of the dataset highlight the practices of
      indigenous and foreign construction firms in sustainable development which can be
      beneficial to stakeholders in environmental protection and mitigating climate
      change issues.

PMID- 30211281
TI  - Experimental datasets on compliance level to minimum standard requirements among
      sandcrete block manufacturers in South Western Nigeria.
AB  - The data in this article are related to "Assessment of Sandcrete Blocks
      Manufacturers 'Compliance to Minimum Standard Requirements by Standard
      Organisation of Nigeria in Southwest, Nigeria" (Ajao et al., 2018). The data
      shows the compliance level of Sandcrete Block Manufacturers to Minimum Standard
      Requirement in Southwest, Nigeria. Experimental procedures carried out on
      aggregates and sandcrete blocks included sieve analysis to determine grading
      distribution sizes and bulk density and compressive strength to determine the
      strength parameters. The results of the experiment were presented in charts and
      graphs.

PMID- 30211282
TI  - Data on assessing fluoride risk in bottled waters in Iran.
AB  - The general goal of this data was to determine the concentration of fluoride and
      assess its risk in waters bottled in Iran. Seventy-one samples of different
      brands of bottled water were collected. Then, the fluoride concentration was
      measured through standard method for water and wastewater experiments. The non
      carcinogenicity risk of fluoride for different groups of infants, children,
      teenagers, and adults was calculated by proper formula. The data presented here
      indicated that the mean concentration of fluoride in bottled waters was 0.272
      mg/L, which is lower than the minimum world health organization (WHO) guideline.
      Further, the mean hazard quotient (HQ) values for fluoride across the groups of
      infants, children, teenagers, and adults with respective values of 0.0363,
      0.2568, 0.1813, and 0.1452 were observed in 0, 1, 1, and 0 cases of HQ>1.
      Generally, in most of the tested brands, HQ value was less than 1, and this value
      was above 1 in only one brand of bottled water.

PMID- 30211283
TI  - Data on Manuka Honey/Gellan Gum composite hydrogels for cartilage repair.
AB  - This work contains original data supporting our research paper "Antibacterial
      effectiveness meets improved mechanical properties: Manuka Honey/Gellan Gum
      composite hydrogels for cartilage repair", Bonifacio et al., in press [1], in
      which innovative composite hydrogels, based on Gellan Gum/Manuka honey/Halloysite
      nanotubes were described as biomaterials for cartilage regeneration. Here the
      composites were further examined by means of Fourier Transform Infrared
      Spectroscopy, in Attenuated Total Reflectance mode (FT-IR/ATR). Materials devoted
      to cartilage replacement must possess adequate fluid permeability and lubricating
      capability, therefore, a deeper investigation on water uptake kinetics of freeze
      dried specimens up to 21 days in PBS was carried out. Moreover, since the
      degradation rate of a biomaterial plays a pivotal role in tissue engineering,
      weight loss measurements of the prepared hydrogels were performed in simulated
      synovial fluid, in phosphate buffer solution (PBS) and in lysozyme. Scanning
      Electron Microscopy images provide insight into the morphology of the freeze
      dried samples. Finally, additional information on Staphylococcus aureus and
      Staphylococcus epidermidis ability to adhere onto the prepared hydrogel
      composites in short times were obtained, as well as the chondrogenic potential of
      the composites assessed by SDS-PAGE followed by Coomassie blue gel staining.

PMID- 30211284
TI  - Smart bandwidth allocation for next generation networks adopting software-defined
      network approach.
AB  - This data article contains information on a new intelligent bandwidth allocation
      model for future network (Smart Allocation). The included data describe the
      topology of the network testbed and the obtained results. Obtained data show the
      effectiveness of the proposed model in comparison with the MAM and RDM bandwidth
      allocation models. In relation to the performances evaluation, a variety of flows
      are used such as: voice over IP (VoIP), video, HTTP, and Internet Control Message
      Protocol (ICMP). The evaluation criteria are: VoIP latency and jitter, Peak
      Signal to Noise Ratio (PSNR) video, retransmission video, goodput, HTTP response
      page, and the Round-Trip Time (RTT) ICMP delay. The presented data are extracted
      based on simulation.

PMID- 30211285
TI  - Dataset on aerosol loading, size and statistics over Nzerekore.
AB  - Inadequate ground measuring equipment is becoming a global challenge. Most
      communities in West Africa rely only on satellite measurements. However, the
      volume of missing dataset in satellite measure over coastal communities is
      alarming. In this research, fifteen years primary (aerosol optical depth) dataset
      was obtained from the Multi-angle Imaging Spectro-Radiometer (MISR). The dataset
      presented in this research will serve as a research background for scientists
      working on the research site.

PMID- 30211286
TI  - Data on optimization of production parameters on Persea Americana (Avocado) plant
      oil biodiesel yield and quality.
AB  - Biodiesel has continued to receive enormous patronage from world energy demand as
      a result of its renewable nature, low toxicity, rapid degradation, robust fuel
      performance and low emission characteristics and its overall environmental
      friendliness. Hence, these data showed the optimization of temperature, catalyst
      concentration and type of catalyst, alcohol type and alcohol to oil molar ratio
      and reaction time on Avocado plant oil biodiesel yield and quality produced via
      alkali-catalyzed transesterification reaction. Data on the quality of the
      biodiesel produced by using the American Standard for Testing Materials (ASTM)
      procedures for biodiesel characterization with different concentrations of
      alcohol and catalyst under varying temperatures and reaction durations are also
      provided. The tested biodiesel properties are the cold flow properties (pour
      point and cloud point) and the critical parameters such as kinematic viscosity at
      40  degrees C, specific gravity at 15  degrees C, flash point, cetane number,
      calorific value, iodine value, acid number and sulphated ash percentage.

PMID- 30211287
TI  - Design and implementation of a Serious Game on neurorehabilitation: Data on
      modifications of functionalities along implementation releases.
AB  - The measurement of users' perception of functionalities in the use of Serious
      Games (SGs) along technology implementation phases may lead to effective changes
      for developing successful user-centered learning tools in the medical field. In
      the present data article, data about usability functionalities along two cycles
      of validation of a SG on neurorehabilitation with final users are described. The
      key principles of usability model used to collect and analyze data and the
      evaluation tool are presented. The modifications of the SG to improve usability
      across implementation phases are detailed. The validation of the SG is described
      in "Engaged in learning neurorehabilitation: development and validation of a
      serious game with user-centered design" (Savazzi et al., in press) [1]. The data
      provided in this article will assist researchers working for developing learning
      technology to optimize their tools in relation to users' needs and expectations.

PMID- 30211288
TI  - Dataset for evaluating fitness index using Adaptive Neuro-Fuzzy Inference System.
AB  - With the current global downturn, the organizations need to develop new
      strategies and innovative approaches to ensure that every aspect of
      sustainability is achieved. For this purpose, the organizations need an indicator
      that measures the fitness if an organization. The purpose of this project is to
      analyze the 'Fitness' of an organization using the dataset related to leanness,
      agility and sustainability in ANFIS (Adaptive Neuro-Fuzzy Inference System) in
      order to determine whether the company is fit enough to sustain in global markets
      or not. The project does so by integrating both neural networks and fuzzy logic
      principles with lean, agility and sustainability principles. FIT manufacturing is
      the integration of Lean, Agile and sustainability manufacturing in one system as
      a whole which would help in attaining maximum output and sustain effectively in
      global markets. FIT Manufacturing adopts an integrated approach towards the use
      of Lean, Agility and Sustainability to achieve a level of fitness that is unique
      to each company. The database in the paper contains lean, agile and sustainable
      indices reviewed by experts. FIT does not prescribe that every aspect of Lean,
      Agile and Sustainability methodologies must be applied to every company, but a
      selective mix of components will provide the optimum conditions for a company to
      prosper.

PMID- 30211289
TI  - Data on ion composition and X-ray diffraction patterns of biosolids from
      wastewater treatment plants in Lufkin and Nacogdoches, Texas, USA.
AB  - The data presented in this article is related to the research article entitled,
      "Structural Characterization and Evaluation of Municipal Wastewater Sludge
      (Biosolids) from two Rural Wastewater Treatment Plants in East Texas, USA"
      (Onchoke et al., [1]). The XRD profiles and composition of biosolids from two
      wastewater treatment plant is presented. This study describes the composition of
      XRD crystalline phase patterns of the wastewater sludge. After the removal of the
      Kalpha2 peaks the d-spacing and hkl values were determined. In addition, the ion
      chromatographic profile of the seven anions ( NO3- , NO2- , Br-, Cl-, F-, SO42- ,
      and PO43- ) in biosolids is presented.

PMID- 30211290
TI  - Infectious diseases mimicking ovarian carcinomatosis.
AB  - Infectious diseases can present similar to ovarian cancer and occur concomitantly
      with ovarian pathology. With increased worldwide travel and migration of
      populations, infections endemic to developing countries can emerge in the United
      States. We present 2 cases of infectious diseases mimicking ovarian
      carcinomatosis. Two Filipino women presented with abdominal distension and had
      evaluations suggestive of advanced gynecologic malignancy. The first patient
      underwent surgery and was found to have peritoneal tuberculosis. Intra-operative
      pathology from the second case revealed ovarian carcinoma with schistosomal
      granulomas of the intestines. Tuberculosis and schistosomiasis should be
      considered when treating women with gynecologic malignancies, especially those
      from abroad or who have spent time overseas. Correct identification of infectious
      etiologies allows for pharmacological intervention and can minimize unnecessary
      surgical procedures.

PMID- 30211291
TI  - Platinum type is key in determining degree of neuropathy.

PMID- 30211292
TI  - Stability of blood-based biomarkers of Alzheimer's disease over multiple freeze
      thaw cycles.
AB  - Introduction: Freeze-thaw instability may contribute to preanalytical variation
      in blood-based biomarker studies. We investigated the effects of up to four
      freeze-thaw cycles on single molecule array immunoassays of serum neurofilament
      light chain and plasma total tau, amyloid beta 1-40 (Abeta40), and Abeta 1-42
      (Abeta42). Methods: Individuals who had peripheral venepuncture during
      investigation of suspected neurodegenerative disease were recruited. After
      standardized preprocessing, 200 MUL of plasma and serum aliquots were stored at 
      80 degrees C within 60 minutes. Aliquots underwent one to four freeze-thaw
      cycles. Results: There was no significant difference across four freeze-thaw
      cycles for serum neurofilament light chain (n = 12), plasma total tau (n = 11),
      or plasma Abeta42 (n = 12). For plasma Abeta40 (n = 14), there were significant
      median reductions by ratios of .96 and .92 at the third and fourth cycles,
      respectively. Discussion: Up to four freeze-thaw cycles do not influence single
      molecule array blood biomarkers of neurofilament light chain, total tau, or
      Abeta42, with at most minor reductions in Abeta40.

PMID- 30211294
TI  - A study of association between platelet volume indices and ST elevation
      myocardial infarction.
AB  - Introduction and objective: ST elevation myocardial infarction (STEMI) is caused
      by formation of a thrombus at a ruptured atheromatous plaque. Larger platelets
      are enzymatically and metabolically more active and play a crucial role in
      thrombus formation. Our objective was to study the association between platelet
      volume indices (mean platelet volume (MPV) and platelet distribution width (PDW))
      and STEMI. Methods: A hospital-based case control study to compare the platelet
      indices of 52 STEMI patients before commencing antiplatelet therapy and age and
      gender matched 52 controls who had no history of ischemic heart disease or
      antiplatelet therapy. Blood samples were collected to EDTA bottles and analyzed
      using Mindray BC 6800 automated analyzer. Results: STEMI patients had
      significantly increased mean MPV and PDW compared to the control group ((8.22 +/-
      0.99 fL vs 7.74 +/- 0.69 fL, p = 0.005) and (15.81 +/- 0.41 fL vs 15.62 +/- 0.33
      fL, p = 0.007) respectively). Significant positive correlation existed between
      MPV and PDW (R = 0.556, p = 0.000) and weak negative correlation in platelet
      count with MPV (R = -0.323, p = 0.019) and PDW (R = -0.309, p = 0.026) of STEMI
      patients. Receiver Operating Characteristic (ROC) curves showed that MPV and PDW
      with cutoff values of 7.55 fL, 15.55 fL and with Area under the curve (AUC) of
      0.640, 0.620 respectively. The sensitivities and specificities were found to be
      73.1%, 69.2% and 61.5%, 55.8% for MPV and PDW respectively. Conclusion: Increased
      MPV and PDW were found to have a significant association with STEMI and this test
      has the potential to be used as a preliminary test to identify high-risk patient
      for myocardial infarction.

PMID- 30211293
TI  - Neuroimaging and neuropsychological assessment of freezing of gait in Parkinson's
      disease.
AB  - Introduction: Freezing of gait (FOG) is a disabling phenomenon characterized by a
      brief, episodic absence or reduction of forward progression of the feet despite
      the intention to walk. It is a common cause of falls and mortality in cases with
      Parkinson's disease (PD). This article reviews neuropsychological and
      neuroimaging studies to date and introduces a new study of multimodal imaging and
      cognition in PD-FOG. Methods: A comprehensive literature search identified
      studies using neuropsychological evaluation and/or neuroimaging to evaluate PD
      FOG. Results: Several studies have evaluated PD-FOG, but few have combined
      neuropsychological and comprehensive neuroimaging and none longitudinally.
      Discussion: A study using a combined approach longitudinally evaluating cognitive
      dysfunction and underlying neural networks in FOG is needed. We introduce the
      framework of a study which demonstrates the use of establishing an infrastructure
      for studying neurodegenerative disorders using the National Institutes of
      Health/National Institute of General Medical Science Center of Biomedical
      Research Excellence grant mechanism.

PMID- 30211295
TI  - Earlier use of capsule endoscopy in inpatients with melena or severe iron
      deficiency anemia reduces need for colonoscopy and shortens hospital stay.
AB  - Background and study aims  Capsule endoscopy(CE) is a well-established
      investigation for iron deficiency anemia (IDA) and melena, usually following
      negative upper and lower endoscopy. We aimed to study the effect of earlier CE in
      the investigative pathway for inpatients with IDA or melena at a large tertiary
      referral centre. Patients and methods  We analyzed inpatients undergoing CE for
      IDA or melena from 2005 to 2017, without signs/symptoms suggesting lower
      gastrointestinal tract pathology. Patients underwent CE following negative upper
      and lower gastrointestinal endoscopy (Group 1), or negative upper
      gastrointestinal endoscopy (UGIE) only (Group 2). Results  One hundred and
      seventy inpatients underwent CE for IDA (n = 44) and melena (n = 126). In Group
      1, 46/95 (48.4%) patients had small bowel (SB) findings. CE found 16/95 (16.8 %)
      gastric and 12/95 (12.6 %) colon findings. Three of 12 patients with colon
      findings required repeat colonoscopy. One hundred and three colon investigations
      were carried out for 95 admissions. In Group 2, 33/75 (44.0%) patients had SB
      findings. There were 12/75 (16.0 %) gastric and 11/75 (14.7 %) colon findings. In
      patients with positive CE, significant colonic findings led to colonoscopy in 10
      of 39 patients (diagnostic yield 6/10). Thirty-six patients had negative CE; 15
      underwent colonoscopy (diagnostic yield 9/15). The remaining 21 of 36 patients
      with no further colonoscopy did not develop adverse outcomes related to colonic
      pathology. Twenty-six colon investigations were carried out in 75 admissions.
      Patients in Group 2 had shorter mean times from admission to CE (5.08 +/- 3.80
      vs. 6.38 +/- 3.80 days; P  = 0.02) and hospital stays (10.5 +/- 9.58 vs. 12.5 +/-
      11.4 days; P  = 0.04) compared to Group 1. Conclusion  Earlier use of CE in
      inpatients with melena or IDA, no signs of lower gastrointestinal pathology and
      negative UGIE resulted in shortened hospital stays, significant DY from both
      small bowel and upper gastrointestinal tract, and two-thirds less unnecessary
      colon investigations without affecting clinical outcomes.

PMID- 30211297
TI  - Endoscopic treatment of esophageal fistulas after esophagectomy with injection of
      an alpha-cyanoacrylate monomer: a phase II study.
AB  - Background and study aims  Interventional endoscopic treatments including the
      application of glue are becoming more frequently used for the treatment of
      esophageal fistulas. However, there are no prospective studies of endoscopic
      treatment for esophageal fistulas. This prospective study aims to investigate the
      efficacy and safety of endoscopic injection of alpha-cyanoacrylate monomer for
      intractable esophageal fistulas. Patients and methods  This single-center
      prospective phase II trial included patients with more than 1 wk of conservative
      medical treatment for intractable esophageal fistulas after esophagectomy. In the
      image-guided therapy suite, a mixture of alpha-cyanoacrylate monomer and oily
      contrast agent in a ratio of 0.3 to 1.7 mL was endoscopically injected through
      the fistula. Results  Twenty-five patients who underwent esophagectomy at
      Wakayama Medical University Hospital were enrolled in this study. The primary
      disease was esophageal cancer in 16 patients (64 %) and gastric cancer in the
      remaining 9 patients (36 %). Complete closure of the esophageal fistula was
      performed in 22 patients after endoscopic injection of alpha-cyanoacrylate
      monomer. The overall success rate was 88 %. There was no fistula recurrence in
      any successful closure cases. Three patients with failed esophageal fistula
      closure had esophageal cancer with cervical esophageal fistulas and required
      reoperation of the fistulectomy under general anesthesia. No complications
      associated with this endoscopic treatment were detected. Conclusions  Endoscopic
      treatment with injection of alpha-cyanoacrylate monomer facilitated healing of
      post-esophagectomy fistula in 88 % of patients without complications. This
      suggests that the treatment is effective and safe for patients with esophageal
      fistulas.

PMID- 30211296
TI  - Impact of the development of an endoscopic eradication program for Barrett's
      esophagus with high grade dysplasia or early adenocarcinoma on the frequency of
      surgery.
AB  - Background and aims  The impact of the advent of an institutional endoscopic
      eradication therapy (EET) program on surgical practice for Barrett's esophagus
      (BE)-associated high grade dysplasia (HGD) or suspected T1a esophageal
      adenocarcinoma (EAC) is unknown. The aims of this study are to evaluate the
      different endoscopic modalities used during development of our EET program and
      factors associated with the use of EET or surgery for these patients after its
      development. Methods  Patients who underwent primary endoscopic or surgical
      treatment for BE-HGD or early EAC at our hospital between January 1992 and
      December 2014 were retrospectively identified. They were categorized by their
      initial modality of treatment during the first year, and the impact over time for
      choice of therapy was assessed by multivariable logistic regression. Results  We
      identified 386 patients and 80 patients who underwent EET and surgery,
      respectively. EET included single modality therapy in 254 (66 %) patients and
      multimodal therapy in 132 (34 %) patients. Multivariable logistic regression
      showed that, for each subsequent study year, EET was more likely to be performed
      in patients who were older ( P  = 0.0009), with shorter BE lengths ( P  <
      0.0001), and with a pretreatment diagnosis of HGD ( P  = 0.0054) compared to
      surgical patients. The diagnosis of EAC did not increase the utilization of EET
      compared to surgery as time progressed ( P  = 0.8165). Conclusion  The
      introduction of an EET program at our hospital increased the odds of utilizing
      EET versus surgery over time for initial treatment of patients who were older,
      had shorter BE lengths or the diagnosis of BE-HGD, but not in patients with EAC.

PMID- 30211298
TI  - Identification of intestinal abnormalities in patients with active pulmonary
      tuberculosis using small bowel capsule endoscopy.
AB  - Background and study aims  Mycobacterium tuberculosis is often detected in the
      feces of patients with active pulmonary tuberculosis. However, no study has
      examined the small intestine using small bowel capsule endoscopy (SBCE). This
      study aimed to investigate intestinal abnormalities in patients with active
      pulmonary tuberculosis. Patients and methods  SBCE was performed in sputum/feces
      smear-positive pulmonary tuberculosis patients. From December 2013 to November
      2016, 15 patients were enrolled from a dedicated tuberculous ward. The primary
      outcome was intestinal abnormalities identified by SBCE. Results  Fourteen
      patients (median age 81 years, range 29 - 91; 3 female) underwent SBCE to the
      terminal ileum. The video was not recorded for one patient who was excluded from
      the analysis. Intestinal lesions, including 5 annular ulcers in 4 patients, were
      observed in 64 % (9/14). In subgroup analysis, prevalence tended to be higher in
      patients undergoing SBCE within 1 month of anti-tuberculous therapy ( P  =
      0.051). Distribution of small intestinal lesions tended to be distal. Four of
      five annular ulcers were located close to the ileocecal valve. Conclusion 
      Prevalence of intestinal lesions in patients with pulmonary tuberculosis is
      higher than expected before (UMIN 000017292).

PMID- 30211299
TI  - Large adrenal cyst masquerading as a pancreatic cystic tumor: a rare diagnosis
      based on endoscopic ultrasound.
AB  - Adrenal cystic lesions constitute a rare finding and usually are diagnosed
      incidentally as retroperitoneal cysts during imaging studies. A major issue,
      especially for the large-sized ones, is their preoperative diagnosis and
      management, as imaging modalities often fail to detect their exact origin prior
      to surgery. We report a case of a big adrenal cyst that was mistakenly diagnosed
      and followed up as pancreatic cystic tail tumor. Our thorough workup, which
      included endoscopic ultrasound (EUS), managed to delineate an adrenal gland
      originated cyst and altered further management of the patient. According to our
      knowledge, this is the first report in literature in which EUS proved its
      superiority over other imaging studies in clarifying the origin of an ambiguous
      big retroperitoneal cyst. We believe that for cases of large retroperitoneal
      cystic lesions, EUS consists the optimal diagnostic and sampling tool.

PMID- 30211300
TI  - Endoscopic full-thickness resection of polyps involving the appendiceal orifice:
      a prospective observational case study.
AB  - Background and study aims  Colorectal polyps involving the appendiceal orifice
      (AO) are difficult to resect with conventional polypectomy techniques and
      therefore often require surgical intervention. These appendiceal polyps could
      potentially be removed with endoscopic full-thickness resection (eFTR) performed
      with a full-thickness resection device (FTRD). The aim of this prospective
      observational case study was to evaluate feasibility, technical success and
      safety of eFTR procedures involving the AO. Patients and methods  This study was
      performed between November 2016 and December 2017 in a tertiary referral center
      by two experienced endoscopists. All patients referred for eFTR with a polyp
      involving the AO that could not be resected by EMR due to more than 50 %
      circumferential involvement of the AO or deep extension into the AO were
      included. The only exclusion criterion was lesion diameter > 20 mm. Results 
      Seven patients underwent eFTR for a polyp involving the AO. All target lesions
      could be reached with the FTRD and retracted into the device. Technical success
      with an endoscopic radical en-bloc and full-thickness resection was achieved in
      all cases. Histopathological R0 resection was achieved in 85.7 % of patients
      (6/7). One patient who previously underwent an appendectomy developed a small
      abscess adjacent to the resection site, which was treated conservatively. Another
      patient developed secondary appendicitis followed by a laparoscopic appendectomy.
      Conclusion  This small exploratory study suggests that eFTR of appendiceal polyps
      is feasible and can offer a minimally invasive approach for radical resection of
      these lesions. However, more safety and long-term follow-up data are needed to
      evaluate this evolving technique.

PMID- 30211301
TI  - Endoscopic augmentation of gastroesophageal junction using a full-thickness
      endoscopic suturing device.
AB  - Background and study aims  This preliminary study was conducted to determine the
      feasibility and safety of endoscopic augmentation of the gastroesophageal
      junction (GEJ) using the Apollo OverStitch endoscopic suturing system in patients
      with gastroesophageal reflux disease (GERD) symptoms. Patients and methods 
      Endoscopic augmentation of GEJ was performed on 10 consecutive patients and the
      data were analyzed retrospectively. Using a double-channel gastroscope affixed to
      the endoscopic suturing platform, interrupted sutures were placed on the gastric
      side of the GEJ in 2 layers in order to create a narrowed and elongated GEJ.
      Results  Technical success was achieved in all patients, including those with a
      history of previous antireflux procedures (n = 7) and those with a hiatal hernia
      (n = 6). The median follow-up duration was 5 mo (range: 2 - 12). The median pre
      procedure GERD-Health Related Quality of Life Questionnaire improved from 20
      (range: 11 - 45) to a post-procedure score of 6 (range: 3 - 25) ( P  = 0.001).
      The median duration of GERD symptom improvement after the procedure was 1 mo
      (range: 0.5 - 4). Adverse events were limited to 1 patient who developed nausea
      and vomiting, which was self-limited. Conclusions  The use of a novel endoscopic
      suturing technique for the treatment of GERD is feasible and safe. The procedure
      resulted in short-term GERD symptom improvement. Further prospective studies
      using refined techniques are currently underway to improve durability and to
      prove efficacy.

PMID- 30211302
TI  - Salvage endoscopic resection in patients with esophageal adenocarcinoma after
      chemoradiotherapy.
AB  - Background and study aims  For early esophageal adenocarcinoma, endoscopic
      resection is an accepted curative treatment with an excellent long-term
      prognosis. Case series from Japan have reported endoscopic resection of residual
      esophageal squamous cell carcinoma after chemoradiotherapy. This is the first
      report describing endoscopic resection of residual esophageal adenocarcinoma
      after chemoradiotherapy. Two patients with advanced esophageal adenocarcinoma had
      been treated with chemoradiotherapy because comorbidity precluded esophageal
      resection. When residual tumor was observed endoscopically, complete remission
      was achieved by salvage endoscopic therapy alone or in combination with argon
      plasma coagulation (APC). Both patients achieved long-term sustained remission
      and died of non-tumor-related causes.

PMID- 30211303
TI  - Endoscopic submucosal dissection for early squamous cell carcinoma in the anal
      canal and Lugol chromoendoscopy for assessment of the lateral margin.
AB  - A 66-year-old man underwent follow-up colonoscopy after colon polypectomy. The
      retroflexed view of the anal canal with white-light imaging revealed a whitish,
      slightly elevated lesion on the dentate line and an ill-defined flat lesion. A
      biopsy of the whitish elevation revealed squamous cell carcinoma (SCC), and
      endoscopic submucosal dissection (ESD) was planned. The lateral margin of the SCC
      was identified by spraying with Lugol's iodine, and the tumor was resected en
      bloc with no complications. The pathological findings were SCC in situ with
      parakeratosis in the whitish elevation and high-grade intraepithelial neoplasia
      in the ill-defined flat lesion, which exhibited a wide iodine-unstained area by
      chromoendoscopy. Early SCC in the anal canal is a rare gastrointestinal cancer,
      and Lugol chromoendoscopy helped visualize the tumor margin for ESD.

PMID- 30211304
TI  - Haptic feedback is useful in remote manipulation of flexible endoscopes.
AB  - Background and study aims  We developed the Endoscopic Operation Robot (EOR)
      version 3, offering built-in haptic feedback and manipulation of the entire scope
      with one hand. Manipulation of the flexible endoscope is done entirely remotely.
      However, inclusion of haptic feedback places a huge burden on the system. Our
      purpose in this study was to determine whether haptic feedback is needed in
      remote manipulation of a flexible endoscope. Methods  Five endoscopists performed
      total colonoscopy using a colonoscopy training model. A trial was conducted in
      which the endoscope was inserted up to the cecum five times with haptic feedback
      and five times without haptic feedback. Insertion time, maximum and mean haptic
      force, and incidence of sigmoid colon overstretching were compared between
      groups. Results  Insertion time was significantly shorter with haptic feedback
      than without, and overstretching of the sigmoid colon was less frequent.
      Insertion could thus be performed without using excessive force. Conclusion 
      Haptic feedback is useful for remote control manipulation of flexible endoscopes.

PMID- 30211305
TI  - Colorectal cancer after negative colonoscopy in fecal immunochemical test
      positive participants from a colorectal cancer screening program.
AB  - Background and study aims  Colorectal cancer (CRC) risk after a positive fecal
      immunochemical test (FIT) and negative colonoscopy is unknown. We aimed to
      ascertain the cumulative incidence of post-colonoscopy colorectal cancer (PCCRC)
      and the manifestation of other lesions that could explain the test positivity in
      individuals with a negative colonoscopy in a population screening program.
      Patients and method  Observational study in participants from the first round of
      a CRC screening program (2010 - 2012) with positive-FIT (>= 20 MUg/g of feces)
      and negative colonoscopy (without neoplasia). A 42- to 76-month follow-up was
      performed searching in the National Health Service database and by a brief
      structured telephonic interview. Results  Of 2659 FIT-positive individuals who
      underwent colonoscopy, 811 (30.5 %) had a negative colonoscopy. Three PCCRC (0.4
      %) were detected within 11 - 28 months and accelerated carcinogenesis was ruled
      out. Among those with normal colonoscopy, 32 (5 %) relevant lesions were detected
      at follow-up. One-third of them (11/32) were significant neoplasias: a gastric
      cancer, a small-bowel lymphoma, six advanced colorectal adenomas, and the three
      PCCRC. The 21 remaining lesions were inflammatory, vascular disorders, or non
      advanced colorectal adenomas. Conclusions  The vast majority (95 %) of
      individuals did not present any subsequent lesion that could explain the FIT
      positivity. The very low incidence (0.4 %) and characteristics of PCCRC observed
      in our cohort reinforce the concept that, although a positive FIT preselects high
      risk individuals, a high quality colonoscopy is the paramount factor in
      preventing PCCRC. Improving quality standards of colonoscopy are required to
      strengthen the current CRC screening strategies.

PMID- 30211306
TI  - Colorectal cancer screening program using FIT: quality of colonoscopy varies
      according to hospital type.
AB  - Background and study aims  To compare the quality of colonoscopy in a population
      based coordinated program of colorectal cancer screening according to type of
      hospital (academic or non-academic). Patients and methods  Consecutive patients
      undergoing colonoscopy after positive FIT (>= 20 ug Hb/g feces) between January
      2009 and September 2016 were prospectively included at five academic and seven
      non-academic public hospitals. Screening colonoscopy quality indicators
      considered were adenoma detection rate, cecal intubation rate, complications and
      bowel preparation quality. Results  A total of 48,759 patients underwent
      colonoscopy, 34,616 (80 %) in academic hospitals and 14,143 in non-academic
      hospitals. Among these cases, 19,942 (37.1 %) advanced adenomas and 2,607 (5.3 %)
      colorectal cancers (CRCs) were detected, representing a total of 22,549 (46.2 %)
      cases of advanced neoplasia. The adenoma detection rate was 64 %, 63.1 % in
      academic hospitals and 66.4 % in non-academic hospitals ( P  < 0.001). Rates of
      advanced adenoma detection, cecal intubation and adequate colonic preparation
      were 45.8 %, 96.2 % and 88.3 %, respectively, and in all cases were lower
      (implying worse quality care) in academic hospitals (45.3 % vs 48.7 %; odds ratio
      [OR] 0.87, 95 % confidence interval [CI] 0.84 - 0.91; 95.9 % vs 97 %; OR 0.48, 95
      % CI 0.38 - 0.69; and 86.4 % vs 93 %; OR 0.48, 95 % CI 0.45 - 0.5; respectively;
      P  < 0.001 in all cases). In 13 patients, all in the academic hospital group, CRC
      was diagnosed after colonoscopy (0.26 cases * 1000 colonoscopies). Rates of CRC
      treated by endoscopy were similar in both types of hospital (30 %). The rate of
      severe complication was 1.2 % (602 patients), with no significant differences by
      hospital type: bleeding occurred in 1/147 colonoscopies and perforation in 1/329.
      One patient died within 30 days after screening colonoscopy. Conclusions  The
      quality of colonoscopy was better in non-academic hospitals. The rate of
      detection of advanced neoplasia was higher in non-academic hospitals and
      correlated with the rate of post-colonoscopy CRC.

PMID- 30211308
TI  - How Do Drosophila Stay Awake during the Daytime? Dopaminergic Neurons Are
      Inhibited by the Pigment Dispersing Factor Signaling Pathway to Promote
      Wakefulness.
AB  - Highlighted Research Paper: Wakefulness Is Promoted during Day Time by PDFR
      Signalling to Dopaminergic Neurons in Drosophila melanogaster, by, Sheetal Potdar
      and Vasu Sheeba.

PMID- 30211309
TI  - Diversity: The Art of Reviewing Independently Together.

PMID- 30211307
TI  - A Tutorial for Information Theory in Neuroscience.
AB  - Understanding how neural systems integrate, encode, and compute information is
      central to understanding brain function. Frequently, data from neuroscience
      experiments are multivariate, the interactions between the variables are
      nonlinear, and the landscape of hypothesized or possible interactions between
      variables is extremely broad. Information theory is well suited to address these
      types of data, as it possesses multivariate analysis tools, it can be applied to
      many different types of data, it can capture nonlinear interactions, and it does
      not require assumptions about the structure of the underlying data (i.e., it is
      model independent). In this article, we walk through the mathematics of
      information theory along with common logistical problems associated with data
      type, data binning, data quantity requirements, bias, and significance testing.
      Next, we analyze models inspired by canonical neuroscience experiments to improve
      understanding and demonstrate the strengths of information theory analyses. To
      facilitate the use of information theory analyses, and an understanding of how
      these analyses are implemented, we also provide a free MATLAB software package
      that can be applied to a wide range of data from neuroscience experiments, as
      well as from other fields of study.

PMID- 30211310
TI  - Antibody biomarker for de novo Parkinson disease: attempted validation.
AB  - Parkinson disease (PD) is a progressive neurodegenerative disease with motor
      symptoms that result from degeneration of midbrain dopaminergic neurons.
      Biomarker research seeks to identify the disease during the pre-symptomatic
      phase, which is a time when therapeutic intervention will be most helpful.
      Previously, we screened a combinatorial peptoid library to search for antibodies
      that are present at much higher levels in the serum of PD patients than in
      control subjects. One such compound, called the PD2 peptoid, was 84% accurate for
      the identification of de novo PD when employed as the capture agent in an enzyme
      linked immunosorbent assay. This peptoid recognized an IgG3 antibody, and IgG3
      levels were also found to be significantly higher in PD vs. control serum. In
      that study we used samples from the NINDS Parkinson's Disease Biomarker Program.
      The current study sought to validate that finding using serum samples from de
      novo and control subjects in the Parkinson's Progression Markers Initiative
      study. We found no difference in levels of antibodies captured by the PD2 peptoid
      in the de novo PD vs. control subjects, and no difference in IgG3 serum levels in
      the two groups. The failure to replicate our previous study appears to be due to
      the lack of difference in serum IgG3 levels between the PD and control subjects
      in the current study.

PMID- 30211311
TI  - Exposure to an extreme environment comes at a sensorimotor cost.
AB  - Long duration space flight is known to induce severe modifications in the
      sensorimotor and musculoskeletal systems. While in-flight strategies including
      physical fitness have been used to prevent the loss of bone and muscle mass using
      appropriate rehabilitative countermeasures, less attention has been put forth in
      the design of technologies that can quickly and effectively assess sensorimotor
      function during missions in space. The aims of the present study were therefore
      (1) to develop a Portable Sensorimotor Assessment Platform (PSAP) to enable a
      crewmember to independently and quickly assess his/her sensorimotor function
      during the NASA's Extreme Environment Mission Operations (NEEMO) and (2) to
      investigate changes in performance of static posture, tandem gait, and lower limb
      ataxia due to exposure in an extreme environment. Our data reveal that measuring
      the degree of upper body balance and gait regularity during tandem walking using
      PSAP provided a sensitive and objective quantification of body movement
      abnormalities due to changes in sensorimotor performance over the duration of
      mission exposure.

PMID- 30211313
TI  - Correlating nuclear morphometric patterns with estrogen receptor status in breast
      cancer pathologic specimens.
AB  - In this pilot study, we introduce a machine learning framework to identify
      relationships between cancer tissue morphology and hormone receptor pathway
      activation in breast cancer pathology hematoxylin and eosin (H&E)-stained
      samples. As a proof-of-concept, we focus on predicting clinical estrogen receptor
      (ER) status-defined as greater than one percent of cells positive for estrogen
      receptor by immunohistochemistry staining-from spatial arrangement of nuclear
      features. Our learning pipeline segments nuclei from H&E images, extracts their
      position, shape and orientation descriptors, and then passes them to a deep
      neural network to predict ER status. After training on 57 tissue cores of
      invasive ductal carcinoma (IDC), our pipeline predicted ER status in an
      independent test set of patient samples (AUC ROC = 0.72, 95%CI = 0.55-0.89, n =
      56). This proof of concept shows that machine-derived descriptors of morphologic
      histology patterns can be correlated to signaling pathway status. Unlike other
      deep learning approaches to pathology, our system uses deep neural networks to
      learn spatial relationships between pre-defined biological features, which
      improves the interpretability of the system and sheds light on the features the
      neural network uses to predict ER status. Future studies will correlate
      morphometry to quantitative measures of estrogen receptor status and, ultimately
      response to hormonal therapy.

PMID- 30211312
TI  - Genomic and expression profiling reveal molecular heterogeneity of disseminated
      tumor cells in bone marrow of early breast cancer.
AB  - Detection of disseminated tumor cells (DTCs) in bone marrow is an established
      negative prognostic factor. We isolated small pools of (~20) EPCAM-positive DTCs
      from early breast cancer patients for genomic profiling. Genome-wide copy number
      profiles of DTC pools (n = 45) appeared less aberrant than the corresponding
      primary tumors (PT, n = 16). PIK3CA mutations were detected in 26% of DTC pools
      (n = 53), none of them were shared with matched PTs. Expression profiling of DTC
      pools (n = 30) confirmed the upregulation of EPCAM expression and certain
      oncogenes (e.g., MYC and CCNE1), as well as the absence of hematopoietic
      features. Two expression subtypes were observed: (1) luminal with dual epithelial
      mesenchymal properties (high ESR1 and VIM/CAV1 expression), and (2) basal-like
      with proliferative/stem cell-like phenotype (low ESR1 and high MKI67/ALDH1A1
      expression). We observed high discordance between ESR1 (40%) and ERRB2 (43%)
      expression in DTC pools vs. the clinical ER and HER2 status of the corresponding
      primary tumors, suggesting plasticity of biomarker status during dissemination to
      the bone marrow. Comparison of expression profiles of DTC pools with available
      data from circulating tumor cells (CTCs) of metastatic breast cancer patients
      revealed gene expression signatures in DTCs that were unique from those of CTCs.
      For example, ALDH1A1, CAV1, and VIM were upregulated in DTC pools relative to
      CTCs. Taken together, analysis of pooled DTCs revealed molecular heterogeneity,
      possible genetic divergence from corresponding primary tumor, and two distinct
      subpopulations. Validation in larger cohorts is needed to confirm the presence of
      these molecular subtypes and to evaluate their biological and clinical
      significance.

PMID- 30211314
TI  - Systemic Treatment of Advanced Hepatocellular Carcinoma in Older Adults.
AB  - Over the past 30 years, the incidence in of hepatocellular carcinoma (HCC) in the
      United States has tripled, largely due to untreated chronic Hepatitis C virus,
      alcoholic hepatitis, and non-alcoholic steatohepatitis (NASH). Additionally, the
      incidence of HCC among South Texas Hispanics is higher than elsewhere in the
      United States. The median age of HCC is 62 years in United States and 67 years in
      South Texas, with over 30% being 70 years of age or older. However, there is
      limited data on how to treat older adults with advanced HCC. In this review, we
      will discuss treatment options for older adults with advanced HCC, further
      emphasizing the need for prospective studies in this population.

PMID- 30211315
TI  - Maximizing Benefit and Minimizing Risk in Medical Imaging Use: An Educational
      Primer for Health Care Professions Students.
AB  - : "I am not young enough to know everything."Oscar Wilde. Background: There is
      insufficient knowledge among providers and patients/caregivers of ionizing
      radiation exposure from medical imaging examinations. This study used a brief,
      interactive educational intervention targeting the topics of best imaging
      practices and radiation safety early in health professions students' training.
      The authors hypothesized that public health, medical, and physician assistant
      students who receive early education for imaging appropriateness and radiation
      safety will undergo a change in attitude and have increased awareness and
      knowledge of these topics. Materials and methods: The authors conducted a 1.5
      hour interactive educational intervention focusing on medical imaging utilization
      and radiation safety. Students were presented with a pre/postquestionnaire and
      data were analyzed using t tests and multivariate analysis of variance. Results:
      A total of 301 students were enrolled in the study. There was 58% (P < .01) and
      85% (P < .01) improvement in attitude and knowledge regarding appropriateness of
      imaging, respectively. The authors also found an 8% increase (P < .01) in
      students who thought informed consent should be obtained prior to pediatric
      computed tomographic imaging. Physical assistant students were more likely than
      medical students to prefer obtaining informed consent at baseline (P = .03).
      Conclusions: A brief educational session provided to health professions students
      early in their education showed an increased awareness and knowledge of the
      utility, limitations, and risks associated with medical imaging. Incorporation of
      a best imagining practice educational session early during medical education may
      promote more thoughtful imaging decisions for future medical providers.

PMID- 30211316
TI  - Diagnostic Efficacy of Serum 1,3-beta-D-glucan for Invasive Fungal Infection: An
      Update Meta-Analysis Based on 37 Case Or Cohort Studies.
AB  - Objective: The aim of this study was to investigate the diagnostic performance of
      serum 1,3-beta-D-gluan as biomarker for invasive fungal infection through meta
      analysis. Methods: The electronic databases of Medline, Cochrane, Embase, Web of
      Science, OVID and CNKI were systematic searched to identified the case-control or
      Cohort studies relevant to diagnostic efficacy of serum 1,3-beta-D-glucan for
      invasive fungal infection. The data of true positive (tp), false positive (fp),
      false negative (fn) and true negative (tn) patients number were extracted from
      each of the original included studies. The diagnostic sensitivity, specificity
      and systematic receiver operating characteristic (SROC) curve were calculated and
      pooled through random or fixed effect method. The publication bias was evaluated
      by the Deek's funnel plot. Results: Thirty-seven relevant studies were fulfilled
      the inclusion criteria and included in our present meta-analysis. The combined
      sensitivity, specificity, positive likely hood ratio (+lr), negative likely hood
      ratio (-lr) and diagnostic odds ratio(dor) for 1,3-beta-D-glucan in diagnosis of
      invasive fungal infectionwere 0.83 (95%CI:0.38-0.61), 0.81 (95%CI:0.80-0.82),
      5.13 (95%CI:3.98-6.62), 0.23 (95%CI:0.18-0.30), and 29.68 (95%CI:18.94-46.52)
      respectively. The pooled area under the ROC curve (AUC) was 0.91.The Deek's
      funnel plot asymmetry test showed there was no publication bias for 1,3-beta-D
      glucan in diagnosis of invasive fungal infection of the included 37 studies.
      Conclusion: Serum 1,3-beta-D-glucan assay was a promising biomarker for invasive
      fungal infection diagnosis.

PMID- 30211317
TI  - Association of MiRNA122 & ADAM17 with Lipids among Hypertensives in Nigeria.
AB  - Background: Dyslipidaemia and hypertension are established major risk factors for
      cardiovascular diseases. The suggested roles of miRNA-122 and ADAM17 in lipid
      metabolism can therefore be applied in the management of metabolic disorders. The
      authors' aim was to determine the association between miRNA-122 and ADAM17, as
      well as the association between miRNA-122 and lipid fractions, in the study
      participants. Method: A comparative cross-sectional study was conducted among 200
      hypertensive patients and 100 non-hypertensive adult controls between May, 2015,
      and June, 2016, in Nigeria. Lipids were analysed with spectrophotometric methods
      whereas ADAM17 and miRNA-122 were analysed with enzyme linked immunosorbent assay
      and quantitative polymerase chain reaction, respectively. Results: The mean
      (standard deviation [SD]) ages of 200 hypertensives and 100 controls were 56.3
      (6.9) and 54.9 (8.3) years, respectively. miRNA-112 and ADAM17 had significantly
      higher values among dyslipidaemic individuvals compared with non-dyslipidaemic
      participants. The correlation between miRNA-122 and ADAM17 levels was strongly
      positive, r=0.82, p<0.05. LDL-cholesterol and total cholesterol also showed
      statistically significant positive correlation with miRNA-122, r=0.53, r=0.51,
      (p< 0.001) respectively. Conclusion: In this study, miRNA-122 showed a strong
      correlation with ADAM17 and a positive correlation with LDL-cholesterol and total
      cholesterol. These findings support the stimulant roles of miRNA-122 and ADAM17
      in lipid metabolism and thus could be used in the management of dyslipidaemia.

PMID- 30211319
TI  - Cuffed Versus Uncuffed Endotracheal Tubes in Pediatrics: A Meta-analysis.
AB  - Background: Cuffed and uncuffed endotracheal tubes are commonly used for
      pediatric patients in surgery and emergency situations. It is still controversial
      which approach should be adopted. The purpose of the study was to compare the
      application of cuffed and uncuffed endotracheal tubes in pediatric patients.
      Methods: We searched PubMed, Web of Science and Cochrane Library for clinical
      trials, which compared the two applications in children. The study
      characteristics and clinical data were summarized by two independent reviewers.
      Meta-analysis of the data was done using Revman 5.3 software. Results: 6 studies
      with 4141 cases were included in this meta-analysis. The pooling analysis showed
      that more patients need tube changes in uncuffed than cuffed tubes (OR: 0.07, 95%
      CI: 0.05-0.10, P < 0.00001). However, there were no differences on intubation
      duration, reintubation occurrence, accidental extubation rate, croup occurrence
      and racemic epinephrine use during the intubation process. Also we didn't find
      any differences on laryngospasm and stridor occurrence after extubation.
      Conclusions: Our study demonstrated that uncuffed endotracheal tubes increased
      the need for tube changes. Other incidences or complications between the two
      groups had no differences. Cuffed tubes may be an optimal option for pediatric
      patients. But more trials are needed in the future.

PMID- 30211318
TI  - The Efficacy and Safety of Enoxaparin: A Meta-analysis.
AB  - The efficacy and safety of enoxaparin (ENOX) in percutaneous coronary
      intervention (PCI) for ST-elevation myocardial infarction (STEMI) remains
      unaddressed. The primary endpoint evaluated was myocardial infarction (MI) or
      death. The secondary endpoint was defined as major bleeding complications.
      Studies comparing the differences in the efficacy and safety of ENOX versus
      unfractionated heparin (UFH) in PCI for the treatment of STEMI were evaluated. We
      presented the odds ratios for individual studies and performed heterogeneity,
      quality assessment, and publication bias analysis. This meta-analysis examined
      four randomized controlled trials (RCTs), and 5585 patients were included (2334
      ENOX patients and 3251 UFH patients). The follow-up period of the endpoints was
      30 or 90 days. Compared with UFH, ENOX significantly reduced the incidence of MI
      (OR, 0.74; P<0.01) and death (OR, 0.74; P<0.03), while there was no significant
      difference between the two treatments on major bleeding (OR,0.81; P=0.33). The
      findings from this meta-analysis suggested that the efficacy and safety of ENOX
      in the treatment of STEMI patients undergoing PCI were significantly better than
      patients treated with UFH. According to this meta-analysis, ENOX is the preferred
      anticoagulant for STEMI patients receiving PCI compared to UFH.

PMID- 30211320
TI  - Thresholding for Medical Image Segmentation for Cancer using Fuzzy Entropy with
      Level Set Algorithm.
AB  - In this study, an effective means for detecting cancer region through different
      types of medical image segmentation are presented and explained. We proposed a
      new method for cancer segmentation on the basis of fuzzy entropy with a level set
      (FELs) thresholding. The proposed method was successfully utilized to segment
      cancer images and then efficiently performed the segmentation of test ultrasound
      image, brain MRI, and dermoscopy image compared with algorithms proposed in
      previous studies. Results showed an excellent performance of the proposed method
      in detecting cancer image segmentation in terms of accuracy, precision,
      specificity, and sensitivity measures.

PMID- 30211321
TI  - Sleep Deprivation in Intensive Care Unit - Systematic Review.
AB  - Background: Sleep disturbances in intensive care unit (ICU) patients have been
      studied worldwide for over 30 years. Factors contributing to sleep disturbances
      are still being identified, and therapeutic procedures aimed at the mitigation of
      such ailments are consequently being developed. Objectives: The aim of this study
      was to review the literature on sleep disturbances in intensive care unit
      patients. Material and Methods: MEDLINE PubMed, OVID, Web of Science, and EBSCO
      databases have been searched using adequate keywords. Results: Sleep disorders in
      ICUs were common among all of the analysed articles. Noise plays a significant
      role in sleep interruption (11.5 - 17% of awakenings). It was noted that the
      introduction of "white noise" into the ICU environment proved unsuccessful in
      reducing the magnitude of changing noise levels. Nursing care activities
      significantly disturb nocturnal rest, and 42.7 such procedures per every 12-hour
      night shift were registered. Aggregating nursing care interventions was suggested
      in order to reduce the number of stimuli experienced by the patient. Conclusion:
      Changes in sleep structure developing during an ICU stay may significantly
      contribute to sleep disorders once the hospitalisation is over.

PMID- 30211322
TI  - Light-driven hydrogen evolution catalyzed by a cobaloxime catalyst incorporated
      in a MIL-101(Cr) metal-organic framework.
AB  - A cobaloxime H2 evolution catalyst with a hydroxo-functionalized pyridine ligand,
      Co(dmgH)2(4-HEP)Cl [dmgH = dimethylglyoxime, 4-HEP = 4-(2-hydroxyethyl)pyridine]
      was immobilized on a chromium terephthalate metal-organic framework (MOF), MIL
      101(Cr), to construct a MOF-catalyst hybrid which displays good photocatalytic H2
      evolution activity. The longevity of the cobaloxime catalyst is increased by MOF
      incorporation, but limited by the stability of the cobalt-pyridine bond under
      turnover conditions.

PMID- 30211323
TI  - Insulin down-regulates cardioprotective SUR2A in the heart-derived H9c2 cells: A
      possible explanation for some adverse effects of insulin therapy.
AB  - Some recent studies associated insulin therapy with negative cardiovascular
      events and shorter lifespan. SUR2A, a KATP channel subunit, regulate
      cardioprotection and cardiac ageing. Here, we have tested whether glucose and
      insulin regulate expression of SUR2A/KATP channel subunits and resistance to
      metabolic stress in heart H9c2 cells. Absence of glucose in culture media
      decreased SUR2A mRNA, while mRNAs of Kir6.2, Kir6.1, SUR1 and IES SUR2B were
      increased. 2-deoxyglucose (50 mM) decreased mRNAs of SUR2A, SUR2B and SUR1, did
      not affect IES SUR2A and IES SUR2B mRNAs and increased Kir6.2 mRNA. No glucose
      and 2-deoxyglucose (50 mM) decreased resistance to an inhibitor of oxidative
      phosphorylation, DNP (10 mM). 50 mM glucose did not alter KATP channel subunits
      nor cellular resistance to DNP (10 mM). Insulin (20 ng/ml) in both physiological
      and high glucose (50 mM) down-regulated SUR2A while upregulating Kir6.1 and
      Kir6.2 (in high glucose only). Insulin (20 ng/ml) in physiological and high
      glucose decreased cell survival in DNP (10 mM). As opposed to Kir6.2, infection
      with SUR2A resulted in titre-dependent cytoprotection. We conclude that insulin
      decreases resistance to metabolic stress in H9c2 cells by decreasing SUR2A
      expression. Lower cardiac SUR2A levels underlie increased myocardial
      susceptibility to metabolic stress and shorter lifespan.

PMID- 30211324
TI  - Predictors of acute throat or esophageal patient reported pain during radiation
      therapy for head and neck cancer.
AB  - Background and purpose: Acute pain during weekly radiotherapy (RT) to the head
      and neck is not well characterized. We studied dose-volume metrics and clinical
      variables that are plausibly associated with throat or esophageal pain as
      measured with a weekly questionnaire during RT. Materials and methods: We
      prospectively collected weekly patient-reported outcomes from 122 head and neck
      cancer patients during RT. The pain score for each question consisted of a four
      level scale: none (0), mild (1), moderate (2), and severe (3). Univariate and
      multivariate ordinal logistic regression analyses were performed to investigate
      associations between both esophageal and throat pain and clinical as well as
      dosimetric variables. Results: In multivariate analysis, age was significantly
      associated with both types of pain, leading to odds ratio (OR) = 0.95 (p = 0.008)
      and OR = 0.95 (p = 0.007) for esophageal and throat pain, respectively. For
      throat pain, sex (OR = 4.12; p = 0.010), with females at higher risk, and
      fractional organ at risk (OAR) mean dose (OR = 3.30; p = 0.014) were
      significantly associated with throat pain. Conclusions: A fractional OAR mean
      dose of 1.1 Gy seems a reasonable cutoff for separating no or mild pain from
      moderate to severe esophageal and throat pain. Younger patients who received RT
      experienced more esophageal and throat pain. Females experienced more throat
      pain, but not esophageal pain.

PMID- 30211325
TI  - Effect of X-ray minibeam radiation therapy on clonogenic survival of glioma
      cells.
AB  - The goal is to compare, in vitro, the efficiency of minibeam radiotherapy (MBRT)
      and standard RT in inducing clonogenic cell death in glioma cell lines. With this
      aim, we report on the first in vitro study performed in an X-ray Small Animal
      Radiation Research Platform (SARRP) modified for minibeam irradiations. F98 rat
      and U87 human glioma cells were irradiated with either an array of minibeams (MB)
      or with conventional homogeneous beams (broad beam, BB). A specially designed
      multislit collimator was used to generate the minibeams with a with of a center
      to-center distance of 1465 (+/-10) MUm, and a PVDR value of 12.4 (+/-2.3)
      measured at 1 cm depth in a water phantom. Cells were either replated for
      clonogenic assay directly (immediate plating, IP) or 24 h after irradiation
      (delayed plating, DP) to assess the effect of potentially lethal damage repair
      (PLDR) on cell survival. Our hypothesis is that with MBRT, a similar level of
      clonogenic cell death can be reached compared to standard RT, when using equal
      mean radiation doses. To prove this, we performed dose escalations to determine
      the minimum integrated dose needed to reach a similar level of clonogenic cell
      death for both treatments. We show that this minimum dose can vary per cell line:
      in F98 cells a dose of 19 Gy was needed to obtain similar levels of clonogenic
      survival, whereas in U87 cells there was still a slightly increased survival with
      MB compared to BB 19 Gy treatment. The results suggest also an impairment of DNA
      damage repair in F98 cells as there is no difference in clonogenic cell survival
      between immediately and delayed plated cells for each dose and irradiation mode.
      For U87 cells, a small IP-DP effect was observed in the case of BB irradiation up
      to a dose of 17 Gy. However, at 19 Gy BB, as well as for the complete dose range
      of MB irradiation, U87 cells did not show a difference in clonogenic survival
      between IP and DP. We therefore speculate that MBRT might influence PLDR. The
      current results show that X-ray MBRT is a promising method for treatment of
      gliomas: future preclinical and clinical studies should aim at reaching a minimum
      radiation (valley) dose for effective eradication of gliomas with increased
      sparing of normal tissues compared to standard RT.

PMID- 30211326
TI  - Carpal tunnel syndrome observed after an arbovirus infection: A preliminary case
      series report.
AB  - Purpose: Report a case series study of individuals who, after having a suspected
      arboviral disease during an epidemic outbreak in north-eastern Brazil, presented
      symptoms of acroparesthesia. Methods: A retrospective evaluation of patients with
      acroparesthesia undertaken between December 2015 and October 2016 following a
      clinical picture suggestive of an arboviral infection. Results: Clinical and
      electrophysiological data were obtained from 29 individuals. 13% were male. All
      presented a main complaint of numbness in the hands, with 86% presenting
      bilateral symptoms. The symptoms started within 60 days of the clinical picture
      in 62% of cases. The electrophysiological study demonstrated CTS in 54 median
      nerves. It was classified as mild in 24.1% of cases, moderate in 32.7%, severe in
      24.1%, very severe in 6.8% and extremely severe in 5.1%. Conclusion: The best
      explanation for the presence of acroparesthesia following an arboviral infection
      may be the narrowing of the carpal tunnel caused by the inflammatory joint
      process usually observed in cases of chikungunya infection. Clinical relevance:
      This is the first study with electrophysiological data that associates arboviral
      infection with CTS.

PMID- 30211327
TI  - Extrapontine myelinolysis effects in intracranial langerhans cell histiocytosis:
      Case report.

PMID- 30211328
TI  - Recurrent autonomic and sensory neuropathy in a patient with anti-ganglionic
      acetylcholine receptor antibodies.
AB  - We report a case of recurrent neuropathy with predominant autonomic and sensory
      involvement whose serum was positive for anti-ganglionic acetylcholine receptor
      (anti-gAChR) antibodies, a diagnostic marker of autoimmune autonomic
      ganglionopathy. An 11-year-old girl complained of numbness and limb pain after
      gastroenteritis. Although hyperalgesia and autonomic dysfunctions, such as
      orthostatic intolerance and gastrointestinal dysmotility subsequently developed,
      these symptoms faded after a few days. Similar sensory and autonomic impairments
      recurred three times within 12 months after the first episode. The sensory and
      autonomic symptoms were rapidly ameliorated by the administration of intravenous
      immunoglobulin (IVIg) at the second and third relapse; however, the symptoms
      persisted even after the administration of IVIg at the fourth relapse. The
      residual symptoms disappeared after methylprednisolone pulse therapy. The
      patient's serum was found to be positive for anti-gAChR antibodies at the second
      relapse, and was negative after methylprednisolone pulse therapy. Further studies
      are needed to clarify the efficacy of treatment and the nosological position in
      the spectrum of neuropathies that are associated with autonomic and sensory
      impairments.

PMID- 30211330
TI  - Enhancing the performance of beech-timber concrete hybrids by a wood surface pre
      treatment using sol-gel chemistry.
AB  - Timber-concrete composites require reliable connections between both components,
      which are usually obtained by metal fasteners or slots in the wood. In this
      study, an alternative approach is presented based on a fully glued connection in
      combination with a primer treated wood surface, to enhance the compatibility and
      the adhesion properties at the interface between beech wood and concrete. Prior
      to the gluing and the concrete application in a wet-on-wet process, the wood
      surface was functionalised with a xerogel obtained by means of a sol-gel process,
      consisting of two layers of silane nanofilms, with different functional groups,
      which are capable of undergoing further chemical crosslinking reactions with the
      adhesive. The coating with its functionalities allows for reducing the
      penetration of the epoxy adhesives into the wood structure and an additional
      chemical connection to the adhesive can be established. The main objective of
      this study was to analyse the effect of the surface treatment on the mechanical
      properties of such composites in 3-point and 4-point bending tests as well as
      push-out-tests. The results showed that the pre-treatment can improve the load
      bearing capacity of the timber-concrete composites, but that a ductile behaviour
      cannot be achieved with the tested adhesives.

PMID- 30211329
TI  - Raccoon (Procyon lotor) biomarker and rabies antibody response to varying oral
      rabies vaccine bait densities in northwestern Pennsylvania.
AB  - Distribution of oral rabies vaccine baits has been used as a strategy for
      managing rabies in the United States since the 1990s. Since that time, efforts
      have been made to improve baiting strategies with a focus on bait density to
      maximize both efficiency and cost effectiveness. An optimal rabies management
      strategy includes a vaccine bait preferred by the target species that is
      distributed at the minimal density needed to achieve population immunity to
      prevent rabies spread. The purpose of our pilot study was to examine the effect
      of 75, 150, and 300 baits/km2 vaccine bait densities on rabies virus neutralizing
      antibody (RVNA) seroprevalence in raccoons (Procyon lotor). Raboral V-RG(r)
      fishmeal polymer baits (Merial Inc. (now a part of Boehringer Ingelheim), Athens,
      Georgia) contain a tetracycline biomarker that was used to estimate bait
      consumption as another measure of intervention impact. Our results suggest that
      raccoon RVNA response increases as bait density increases, but the effect may not
      be sufficient to justify the cost except in the case of contingency actions or an
      epizootic. Non-target species, especially opossums (Didelphis virginianus) in
      certain areas, should be considered when determining an appropriate bait density
      to ensure sufficient baits are available for consumption by the target species.

PMID- 30211331
TI  - Effectiveness of cognitive, developmental, and behavioural interventions for
      Autism Spectrum Disorder in preschool-aged children: A systematic review and meta
      analysis.
AB  - Background: Autism spectrum disorder (ASD) is characterised by significant
      impairment in social communication and the presence of restrictive and repetitive
      behaviour or interest. Intervention during early childhood could decrease ASD
      symptoms. We aimed to identify the most effective intervention based on
      cognitive, developmental, and behavioural approaches and the factors that impact
      the effectiveness of the intervention. Methods: We performed a systematic review
      and meta-analysis of existing interventions for ASD in preschool-aged children.
      Electronic databases were searched for related articles with randomised
      controlled trial (RCT) designs published between 2001 to 2015. Outcome measures
      were communication, behavioural and cognitive skills, reported as standardised
      mean differences (SMD) compared to a control group. A Random-effects model was
      utilised to calculate the pooled estimate effect. Between-study variability was
      also assessed. The registering number of this study is CRD42017035354. Findings:
      Out of the initial 5174 studies that were identified, there were 14 RCTs (746
      children) that were included in the final systematic review and meta-analysis.
      Pooled estimate effect provided by random-effects model was 0.23 (95% confidence
      interval, CI [0.08-0.37]) with no between-study heterogeneity (I2 = 0.00%, p =
      0.0018). Three studies of music therapy interventions provided the greatest
      outcome effects with a shorter duration and lower intensity. SMD for music
      therapies ranged from 0.40 to 0.62 with 95% CI [0.22 to 1.85]. The quality of the
      health care provider, the duration, and the intensity of intervention played an
      important role in the effectiveness of the intervention. Interpretation: Music
      therapy appears to be an effective tool for improving social interaction in
      preschool-aged children with ASD. However, more evidence-based trials are
      required to further validate the effectiveness of music therapy in ASD.

PMID- 30211332
TI  - Computational and experimental research on mechanism of cis/trans isomerization
      of oleic acid.
AB  - The harm of trans-fatty acids to health has aroused public concern. It is
      believed that the main source of trans-fatty acids in diets is the isomerization
      of unsaturated fatty acids in edible oils during cooking. However, the
      information on the isomerization mechanism is very limited. In this paper, we
      used oleic acid, an unsaturated fatty acid, as a simplified model for edible oil
      and investigated the mechanism of cis/trans isomerization by computation and
      experiments. The computational results show that Rc-O-O-H is a very important
      intermediate, and the cleavage of O-O bond in Rc-O-O-H is the rate-controlling
      step during the cis/trans isomerization. Using the ATR-FTIR measurements, the
      contents of elaidic acid were measured quantitatively in sites. The experimental
      results indicate that the cis/trans isomerization of oleic acid can occur
      obviously only under oxidizing condition when the temperature is higher than 120 
      degrees C.

PMID- 30211333
TI  - Occurrence of Cryptosporidium spp. and Cystoisospora belli among adult patients
      with diarrhoea in Maputo, Mozambique.
AB  - Infections with Cryptosporidium spp. and Cystoisospora belli are important causes
      of diarrhoea in HIV patients. Nevertheless, information concerning these two
      parasites is scarce in many African countries, including Mozambique. In this
      study occurrence of Cryptosporidium spp. and C. belli was investigated by
      microscopy of stool specimens from 108 adult diarrhoeal patients, most with a
      confirmed HIV diagnosis. The Cryptosporidium isolates were further characterized
      by molecular methods. Cryptosporidium and C. belli oocysts were found in 8.3%
      (9/108), and 25.0% (27/108) of the study participants, respectively. Species
      identification was possible for all Cryptosporidium isolates with available DNA.
      The following Cryptosporidium species were detected (number of cases within
      parentheses): C. parvum (3), C. hominis (3), C. felis (1), and C. hominis/C.
      parvum (1). Subtyping targeting the gp60 gene revealed two C. hominis isolates
      with subtype IaA23R3, one C. parvum isolate with IIcA5G3d, and one with IIeA12G1.
      In summary the occurrence of C. hominis and anthroponotic subtypes of C. parvum
      indicates that the main route of Cryptosporidium transmission in the present
      study population was human to human (direct or via food and water). The high
      prevalence of C. belli highlights the need for early diagnosis of this parasite,
      for which a treatment exists.

PMID- 30211334
TI  - Lack of 17beta-estradiol reduces sensitivity to insulin in the liver and muscle
      of male mice.
AB  - The importance of estrogens for glucose homeostasis has been demonstrated by
      clinical, pharmacological, and experimental studies. Male mice lacking the
      aromatase gene (ArKO mice), which encodes an enzyme involved in estrogen
      synthesis, develop glucose- and insulin-intolerance. However, it remains unclear
      whether insulin signaling is actually impaired in the liver and muscle of ArKO
      mice. We examined the effects of estrogen-deficiency on insulin signaling by
      quantifying phosphorylation levels of protein kinase B (Akt) in the liver and
      muscle and by examining the expression levels of insulin-target genes in the
      liver. Insulin administration enhanced phosphorylation levels of Akt in the liver
      and muscle of wild-type (WT) mice, ArKO mice, and ArKO mice supplemented with
      17beta-estradiol (E2), but insulin was less effective in ArKO mice. Gene
      expression analysis revealed that alterations induced by insulin in WT liver were
      also observed in ArKO liver, but the degree of altered expression in a subset of
      genes was smaller in ArKO mice than in WT mice. E2 supplementation improved the
      insulin responses of some genes in ArKO mice. Thus, these findings suggest that
      insulin signaling in the liver and muscle of ArKO mice is less efficient than in
      WT mice, which contributes to whole-body glucose intolerance in ArKO mice.

PMID- 30211335
TI  - Bioleaching of heavy metals from pig manure with indigenous sulfur-oxidizing
      bacteria: effects of sulfur concentration.
AB  - The purpose of this work was to study the sulfur concentration on bioleaching of
      heavy metals from pig manure employing indigenous sulfur-oxidizing bacteria.
      Also, the variations in physicochemical properties of pig manure before and after
      bioleaching were investigated. The results showed that sulfur concentration
      significantly affected the rate of acidification, sulfate production and metal
      solubilization during pig manure bioleaching process. A Michaelis-Menten type
      equation was utilized to interpret the relationships between sulfur
      concentration, sulfate production and metal solubilization in the bioleaching
      process. The rates of metal solubilization during pig manure bioleaching were
      well described by a first order kinetic equation related to time. After 12 days
      of bioleaching, 93%-97% of Zn, 96%-98% of Mn and 48%-94% of Cu were leached out
      from pig manure, respectively. The metals remaining in the pig manure residual
      were mainly existed in stable forms. In addition, elemental analysis showed that
      bioleaching process could significantly modify the dewaterbility and organic
      composition of pig manure. However, fertility analysis found that 9.0%-19.1% of
      nitrogen, 68.5%-71.0% of phosphorus, 76.5%-78.8% of potassium and 47.5%-49.4% of
      the total organic carbon (TOC) were lost from pig manure in the bioleaching
      process. Therefore, bioleaching process used in this study could be applied to
      remove heavy metals effectively from the pig manure, but more detailed studies
      need to be done to decrease the nutrients loss from pig manure.

PMID- 30211336
TI  - Constitutive activity of transient receptor potential vanilloid type 1 triggers
      spontaneous firing in nerve growth factor-treated dorsal root ganglion neurons of
      rats.
AB  - Dorsal root ganglion (DRG) neurons cultured in the presence of nerve growth
      factor (NGF, 100 ng/ml) often show a spontaneous action potential. Underlying
      mechanisms of this spontaneous firing were examined using the patch clamp
      technique. The spontaneous firing in the on-cell configuration was abolished by a
      decrease in the Na+ concentration and by the TRPV1 antagonists capsazepine (10
      MUM) and BCTC (1 MUM). These responses were accompanied by hyperpolarization of
      the resting potential. The holding current observed in neurons voltage clamped at
      -60 mV in the whole-cell configuration was significantly larger in the neurons
      that fired spontaneously, indicating that these neurons had an additional cation
      conductance that caused depolarization and triggered action potentials. The
      holding current in the firing neurons was decreased by extracellular Na+
      reduction, capsazepine and BCTC. The amplitudes of the capsazepine- or BCTC
      sensitive component of the holding current in the spontaneously firing neurons
      were ten times as large as those recorded in the other neurons showing no
      spontaneous firing. However, the amplitudes of the current responses to capsaicin
      (1 MUM) were not different regardless of the presence of spontaneous firing or
      treatment with NGF. These results indicate that chronic NGF treatment of cultured
      DRG neurons in rats induces a constitutively active cation conductance through
      TRPV1, which depolarizes the neurons and triggers spontaneous action potentials
      in the absence of any stimuli. Since NGF in the DRG is reported to increase after
      nerve injury, this NGF-mediated regulation of TRPV1 may be a cause of the
      pathogenesis of neuropathic pain.

PMID- 30211338
TI  - Effects of primatological training on anthropomorphic valuations of emotions.
AB  - Anthropomorphism implies the attribution of human like emotions and cognition to
      non-human animals. This tendency may be conditioned by similar morphologies
      between mammals and is particularly important in primatology. Some neurocognitive
      findings suggest that prefrontal brain activity associated to conceptual learning
      influences anthropomorphic judgments, nevertheless, individual differences are
      also presented indicating that training on primate behavior may influence
      anthropomorphism. We identified and interpreted brain activity registered by
      functional magnetic resonance imaging while seven trained primatologists (39.42
      +/- 10.86 yr.) inferred emotions in human primates, non-human primates and non
      primate animals; comparisons were made with seven matched scholars with no
      primatological training (38.71 +/- 9.34 yr.). Primatologists manifested
      cerebellar, occipital and frontal activity related to sensory and motor processes
      when valuating humans and non-human primates, but not for other animals. So,
      primatological training and experience may elicit brain plasticity processes
      allowing inner motor and sensory models through frontal and cerebellar
      interactions.

PMID- 30211337
TI  - Neurodegeneration in the olfactory bulb and olfactory deficits in the Ccdc66 -/-
      mouse model for retinal degeneration.
AB  - The Ccdc66-deficient (Ccdc66 -/-) mouse model exhibits slow progressive retinal
      degeneration. It is unclear whether CCDC66 protein also plays a role in the
      wildtype (WT; Ccdc66 +/+) mouse brain and whether the lack of Ccdc66 gene
      expression in the Ccdc66 -/- mouse brain may result in morphological and
      behavioral alterations. CCDC66 protein expression in different brain regions of
      the adult WT mouse and in whole brain during postnatal development was quantified
      by SDS-PAGE and Western blot. Ccdc66 reporter gene expression was visualized by X
      gal staining. Selected brain regions were further analyzed by light and electron
      microscopy. In order to correlate anatomical with behavioral data, an olfactory
      habituation/dishabituation test was performed. CCDC66 protein was expressed
      throughout the early postnatal development in the WT mouse brain. In adult mice,
      the main olfactory bulb exhibited high CCDC66 protein levels comparable to the
      expression in the retina. Additionally, the Ccdc66 -/- mouse brain showed robust
      Ccdc66 reporter gene expression especially in adult olfactory bulb glomeruli, the
      olfactory nerve layer and the olfactory epithelium. Degeneration was detected in
      the Ccdc66 -/- olfactory bulb glomeruli at advanced age. This degeneration was
      also reflected in behavioral alterations; compared to the WT, Ccdc66 -/- mice
      spent significantly less time sniffing at the initial presentation of unknown,
      neutral odors and barely responded to social odors. Ccdc66 -/- mice develop
      substantial olfactory nerve fiber degeneration and alteration of olfaction
      related behavior at advanced age. Thus, the Ccdc66 -/- mouse model for retinal
      degeneration adds the possibility to study mechanisms of central nervous system
      degeneration.

PMID- 30211339
TI  - Tele-transitions of care. A 12-month, parallel-group, superiority randomized
      controlled trial protocol, evaluating the use of telehealth versus standard
      transitions of care in the prevention of avoidable hospital readmissions.
AB  - Introduction: Comprehensive transitions of care, reduce dangerous hospital
      readmissions. Telehealth offers promise, however few guidelines aid clinicians in
      introducing it in a feasible way while addressing the needs of a multi-comorbid
      population. Physician adoptability remains a significant barrier to the use of
      Telehealth due to data overload, concerns for disruptive workflows and uncertain
      practices. The methods proposed aid clinicians in implementing Telehealth
      training and research with limited resources to reach patients who need clinical
      surveillance most. This study introduces a new workflow for addressing tele
      transitions of care, using risk stratification, remote patient monitoring, and
      patient-centered virtual visits. We propose a new communication tool which
      facilitates adoption. We take a clinically meaningful approach in assessing
      avoidable hospital readmissions, which can lead to further quality improvements
      and improved patient care. Methods: This study design is a parallel-group,
      superiority, randomized controlled trial in which 180 patients are enrolled in
      the standard of care or Telehealth arms and evaluated for 30-days post
      hospitalization. The Telehealth group receives daily vitals surveillance with a
      "teledoc", a senior resident physician, who performs weekly virtual visits. The
      endpoint is 30-day hospital readmission. Patient data is collected on hospital
      utilization, patient self-management, physician and patient experience.
      Discussion: Our protocol introduces a novel study design with existing clinical
      trainees, to provide comprehensive tele-transitions of care to reduce avoidable
      readmissions.

PMID- 30211340
TI  - Preliminary analysis of the effect of Stevia (Stevia rebaudiana) in patients with
      chronic kidney disease (stage I to stage III).
AB  - Background: Stevia, Stevia rebaudiana (Bertoni), has become an important economic
      plant for its commercial use as a sweetener. Stevia plays a significant role in
      the healthcare practice of different cultures and in population. Previous animal
      and clinical studies demonstrated the efficacy of Stevia against chronic diseases
      like diabetes and hypertension. This study aimed to investigate the beneficial
      effect of Stevia in chronic kidney disease (CKD) patients after three (3) months
      of treatment along with the conventional antihypertensive and anti diabetic
      medications. Methods: A prospective, interventional, randomized, single-blind,
      placebo-controlled trial has been done with 97 participants. Stevia capsule (250
      mg) or matching placebo was given to the participants twice daily along with
      Angiotensin-II Receptor Blocker (ARB) and/or Ca2+ Channel Blocker (CCB). First
      follow up visits were done after 3 months of the interval. Blood and urine
      samples were collected for the biochemical tests. A structured questionnaire was
      used for the baseline assessment. Informed consent was taken from each
      participant. Results: Both hypertension and diabetes were found to be associated
      with CKD. Most of the participants (52.3%) of Stevia group were in CKD Stage II.
      Significant changes were found in Serum creatinine (p < 0.027), Serum Uric acid
      (p < 0.009), Fasting blood sugar (p < 0.041) and Postprandial blood sugar (p <
      0.013) and Microalbumin (p < 0.041) level in the treatment group. Conclusion: The
      initial result demonstrated that Stevia has the potential for a significant
      improvement of some biochemical parameters in CKD patients. After completion of
      the nine (9) months clinical trial, the constructive effect of Stevia can be
      confirmed in this group of patients.

PMID- 30211341
TI  - Inadvertent corneal pigmentation following cosmetic blepharopigmentation.
AB  - Purpose: To present a case of inadvertent corneal pigmentation as a complication
      of cosmetic eyelid tattooing. Observations: A 63 year old woman presented with
      left eye redness and irritation 3 days after undergoing permanent eyeliner
      tattooing of her upper and lower eyelids. On ocular examination a black
      pigmentation of the nasal cornea in her left eye was observed, with associated
      conjunctival injection. Initial slit lamp attempts of pigment removal were
      unsuccessful. A surgical attempt to scrape the pigment in the stroma was only
      partially successful due to the penetration of pigment particles in between
      stromal lamellae. Microanalysis spectroscopy was performed on a specimen of
      pigment taken from the eyelashes in order to attain the chemical properties of
      the material and assist with further therapeutic strategy. The analysis revealed
      an organic inert nature of the material (mostly carbon and oxygen) and ruled out
      presence of dangerous components such as copper and lead. Due to minimal
      inflammatory reaction and the non-central location of the corneal pigmentation,
      the patient remained under close observation, treated with lubrication and no
      further interventions, until complete resolution by 6 weeks. Conclusions and
      importance: While the procedure of cosmetic blepharopigmentation is considered
      relatively safe, it bares many possible complications, ranging from mild dermal
      irritation to vision-threatening conditions. Our case of inadvertent
      keratopigmentation demonstrates the potential dangers of this procedure, and the
      importance of medical supervision and intervention in cases of complications.
      Vision preservation in this case was enabled by the midperipheral location of the
      pigment penetration.

PMID- 30211343
TI  - eIF4E phosphorylation regulates ongoing pain, independently of inflammation, and
      hyperalgesic priming in the mouse CFA model.
AB  - Mitogen activated protein kinase-interacting kinase (MNK)-mediated
      phosphorylation of the mRNA cap binding protein eIF4E controls the translation of
      a subset of mRNAs that are involved in neuronal and immune plasticity. MNK-eIF4E
      signaling plays a crucial role in the response of nociceptors to injury and/or
      inflammatory mediators. This signaling pathway controls changes in excitability
      that drive acute pain sensitization as well as the translation of mRNAs, such as
      brain-derived neurotrophic factor (BDNF), that enhance plasticity between dorsal
      root ganglion (DRG) nociceptors and second order neurons in the spinal dorsal
      horn. However, since MNK-eIF4E signaling also regulates immune responses, we
      sought to assess whether decreased pain responses are coupled to decreased
      inflammatory responses in mice lacking MNK-eIF4E signaling. Our results show that
      while inflammation resolves more quickly in mice lacking MNK-eIF4E signaling,
      peak inflammatory responses measured with infrared imaging are not altered in the
      absence of this signaling pathway even though pain responses are significantly
      decreased. We also find that inflammation fails to produce hyperalgesic priming,
      a model for the transition to a chronic pain state, in mice lacking MNK-eIF4E
      signaling. We conclude that MNK-eIF4E signaling is a critical signaling pathway
      for the generation of nociceptive plasticity leading to acute pain responses to
      inflammation and the development of hyperalgesic priming.

PMID- 30211345
TI  - Medial Quadriceps Tendon Femoral Ligament Reconstruction After Patellectomy: A
      Treatment for a Dislocating Quadriceps Tendon.
AB  - The medial quadriceps tendon femoral ligament (MQTFL) reconstruction is an
      alternative to the patellar bony fixation of the medial patellofemoral ligament
      reconstruction for the treatment of lateral patellofemoral dislocation. We
      describe the first report of a unique application of this technique in a patient
      with a previous patellectomy to treat a dislocating quadriceps tendon. An active
      59-year-old Caucasian man presented 25 years after patellectomy with a
      dislocating quadriceps tendon and significant dysfunction. Stabilization of the
      knee extensor mechanism with an MQTFL reconstruction and retensioning of the
      quadriceps complex by tibial tubercle distalization provided stability and
      improved function. Extensor tendon instability is a rare complication after
      patellectomy that can cause significant pain and dysfunction. Successful
      stabilization of the quadriceps mechanism through an MQTFL reconstruction can
      provide excellent patient satisfaction and functional results. This technique may
      have implications for patellofemoral instability surgeries and in cases of knee
      extensor dysfunction after total knee arthroplasty.

PMID- 30211346
TI  - Posterior Rotator Cuff-sparing Total Shoulder Arthroplasty: Three Cases.
AB  - The traditional total shoulder arthroplasty approach uses a subscapularis
      takedown through tenotomy, peel, or lesser tuberosity osteotomy. Recently, a
      subscapularis split, rotator interval, and sub-subscapularis approach have been
      developed to spare the rotator cuff and provide improved functional outcomes for
      patients. Rotator cuff-sparing total shoulder arthroplasty may improve
      postoperative pain, rehabilitation, and subscapularis function and strength.
      Here, the first three patients treated with a rotator cuff-sparing posterior
      approach that uses the interval between the teres minor and infraspinatus and an
      in situ osteotomy are described.

PMID- 30211344
TI  - Reliable Pan-Cancer Microsatellite Instability Assessment by Using Targeted Next
      Generation Sequencing Data.
AB  - Purpose: Microsatellite instability (MSI)/mismatch repair (MMR) status is
      increasingly important in the management of patients with cancer to predict
      response to immune checkpoint inhibitors. We determined MSI status from large
      panel clinical targeted next-generation sequencing (NGS) data across various
      solid cancer types. Methods: The MSI statuses of 12,288 advanced solid cancers
      consecutively sequenced with Memorial Sloan Kettering-Integrated Mutation
      Profiling of Actionable Cancer Targets clinical NGS assay were inferred by using
      MSIsensor, a program that reports the percentage of unstable microsatellites as a
      score. Cutoff score determination and sensitivity/specificity were based on MSI
      polymerase chain reaction (PCR) and MMR immunohistochemistry. Results: By using
      an MSIsensor score >= 10 to define MSI high (MSI-H), 83 (8%) of 996 colorectal
      cancers (CRCs) and 42 (16%) of 260 uterine endometrioid cancers (UECs) were MSI
      H. Validation against MSI PCR and/or MMR immunohistochemistry performed for 138
      (24 MSI-H, 114 microsatellite stable [MSS]) CRCs, and 40 (15 MSI-H, 25 MSS) UECs
      showed a concordance of 99.4%. MSIsensor also identified 68 MSI-H/MMR-deficient
      (MMR-D) non-CRC/UECs. Of 9,591 non-CRC/UEC tumors with MSS MSIsensor status, 456
      (4.8%) had slightly elevated scores(>=3 and <10) of which 96.6% with available
      material were confirmed to be MSS by MSI PCR. MSI-H was also detected and
      confirmed in three non-CRC/UECs with low exonic mutation burden (< 20). MSIsensor
      correctly scored all 15 polymerase epsilon ultra-mutated cancers as negative for
      MSI. Conclusion: MSI status can be reliably inferred by MSIsensor from large
      panel targeted NGS data. Concurrent MSI testing by NGS is resource efficient, is
      potentially more sensitive for MMR-D than MSI PCR, and allows identification of
      MSI-H across various cancers not typically screened, as highlighted by the
      finding that 35% (68 of 193) of all MSI-H tumors were non-CRC/ UEC.

PMID- 30211347
TI  - Bilateral Hip Fracture in Adolescents With Antiretroviral Treatment.
AB  - Tenofovir is a nucleotide reverse transcriptase inhibitor, a commonly prescribed
      antiretroviral as part of initial therapy. It is widely used and has been
      recognized as a cause of acquired Fanconi syndrome, a disorder characterized by
      renal tubular dysfunction, which leads to hypophosphatemia, hypokalemia, and
      metabolic acidosis, as well as symptoms of polyuria and dehydration, which can
      ultimately lead to defects in bone mineralization and increase risk of fracture.

PMID- 30211348
TI  - JAAOS Global Research & Reviews.

PMID- 30211342
TI  - Therapeutic opportunities for pain medicines via targeting of specific
      translation signaling mechanisms.
AB  - As the population of the world ages and as more and more people survive diseases
      that used to be primary causes of mortality, the incidence of severe chronic pain
      in most of the world has risen dramatically. This type of pain is very difficult
      to treat and the opioid overdose epidemic that has become a leading cause of
      death in the United States and other parts of the world highlights the urgent
      need to develop new pain therapeutics. A common underlying cause of severe
      chronic pain is a phenotypic change in pain-sensing neurons in the peripheral
      nervous system called nociceptors. These neurons play a vital role in detecting
      potentially injurious stimuli, but when these neurons start to detect very low
      levels of inflammatory meditators or become spontaneously active, they send
      spurious pain signals to the brain that are significant drivers of chronic pain.
      An important question is what drives this phenotypic shift in nociceptors from
      quiescence under most conditions to sensitization to a broad variety of stimuli
      and spontaneous activity. The goal of this review is to discuss the critical role
      that specific translation regulation signaling pathways play in controlling gene
      expression changes that drive nociceptor sensitization and may underlie the
      development of spontaneous activity. The focus will be on advances in
      technologies that allow for identification of such targets and on developments in
      pharmacology around translation regulation signaling that may yield new pain
      therapeutics. A key advantage of pharmacological manipulation of these signaling
      events is that they may reverse phenotypic shifts in nociceptors that drive
      chronic pain thereby creating the first generation of disease modifying drugs for
      chronic pain.

PMID- 30211349
TI  - The Journal Impact Factor of Orthopaedic Journals Does not Predict Individual
      Paper Citation Rate.
AB  - Background: The journal impact factor (JIF) is thought to reflect the average
      number of citations an article will receive and therefore can influence study
      impact and clinical decision making. However, analysis of citation rates across
      multiple scientific and research domains has shown that most articles will not
      reach this expected number of citations. This phenomenon is known as citation
      skew and it has not previously been examined in the orthopaedic literature. The
      objective of this study was to determine the extent to which citation skew exists
      within orthopaedic journals and thus to determine whether the JIF in the
      orthopaedic literature reflects individual study citation rates. Methods: We used
      data from the Thomson Reuters (now Clarivate Analytics) Web of Science to
      determine the 2015 JIF and citation distribution for all orthopaedic journals
      listed in the database. We calculated the percentage of articles with fewer
      citations than the JIF for each journal. Finally, we analyzed the citation
      distribution within groups of orthopaedic subspecialty publications. Results: We
      identified a total of 74 orthopaedic journals and 29,296 publications for the
      years 2013 and 2014. Across all orthopaedic journals, 85% of published articles
      are cited fewer times than the JIF would indicate. The median number of citations
      of all articles was zero for all journals (interquartile range = 0-0) except for
      seven journals, for which the median number of citations per article was 1.
      Conclusion: Citation skew is prevalent across the orthopaedic literature. Most
      published work is not cited in the first 2 years following publication, and the
      JIFs are the result of a few highly cited articles. The assessment of an
      individual orthopaedic study's quality should not be determined by the JIF but
      rather by direct evaluation of the methodology, relevance, and appropriateness of
      the study's conclusions.

PMID- 30211350
TI  - Anatomic Knowledge and Perceptions of the Adequacy of Anatomic Education Among
      Applicants to Orthopaedic Residency.
AB  - Background: The time dedicated to the study of human anatomy within medical
      school curriculums has been substantially reduced. The effect of this on the
      knowledge of incoming orthopaedic trainees is unknown. The current study aimed to
      evaluate both the subjective perceptions and objective anatomic knowledge of
      fourth-year medical students applying for orthopaedic residency. Methods: A
      multicenter prospective study was performed that assessed 224 students during the
      course of their interview day for an orthopaedic residency. Participants provided
      demographic data and a subjective assessment of the quality of their anatomic
      education, and completed either an upper or lower extremity anatomic examination.
      Mean total scores and subscores for various anatomic regions and concepts were
      calculated. Results: Students on average rated the adequacy of their anatomic
      education as 6.5 on a 10-point scale. Similarly, they rated the level of
      importance their medical school placed on anatomic education as 6.2 on a 10-point
      scale. Almost 90% rated the time dedicated to anatomy as good or fair. Of six
      possible methods for learning anatomy, dissection was rated the highest.On
      objective examinations, the mean score for correct answers was 44.2%. This
      improved to 56.4% when correct and acceptable answers were considered. Regardless
      of anatomic regions or concepts evaluated, percent correct scores did not reach
      50%. There were no significant correlations between performance on the anatomic
      examinations and either prior academic performance measures or the student's
      subjective assessment of their anatomic education. Conclusions: Current students
      applying into orthopaedic residency do not appear to be adequately prepared with
      the prerequisite anatomic knowledge. These deficits must be explicitly addressed
      during residency training to produce competent, safe orthopaedic surgeons.

PMID- 30211351
TI  - Radiographic Patterns of Radiocarpal and Midcarpal Arthritis.
AB  - Introduction: The purpose of this study was to determine the specific locations
      of radiocarpal and/or midcarpal joint osteoarthritis (RC/MC OA). Methods: A total
      of 1,007 wrist radiographs were screened for the presence of RC/MC OA. The
      locations of the degenerative changes were identified. In addition, the observers
      then determined whether the observed patterns fell under the scapholunate
      advanced collapse (SLAC) pattern. Results: The SLAC pattern did not represent the
      majority of observed degenerative changes. Almost one-third of the patients had
      degenerative changes present at the radiolunate or scaphocapitate articulations
      in the absence of radioscaphoid changes. Women have a lower risk of arthritis
      compared with men (odds ratio, 0.306; P < 0.05). Increasing age correlated with
      the presence of arthritis (odds ratio, 1.05; P < 0.05). Conclusion: Contrary to
      the previous reports in the literature, our cohort demonstrated that <50% of
      wrist OA fell into the category of SLAC arthritis.

PMID- 30211352
TI  - Posttraumatic Pigmented Villonodular Synovitis of the Elbow After Occult
      Fracture: A Literature Review.
AB  - Pigmented villonodular synovitis (PVNS) is a disease rarely found in the elbow.
      In the setting of previous trauma, there are no documented reports of PVNS
      occurring in the posttraumatic state. We report a case of elbow PVNS in a 16-year
      old male with a history of traumatic injury to the supracondylar humerus and
      olecranon, resulting in nondisplaced fractures, diagnosed 3 years prior to
      presentation. We diagnosed posttraumatic PVNS of the elbow using a combination of
      plain radiographs, ultrasonography, and MRI, along with an infectious,
      hematologic, and rheumatologic workup. This workup cumulates in open elbow
      debridement of synovial tumor, with pathology confirming our preoperative
      diagnosis of PVNS. A literature search and review of PVNS in the elbow yield only
      54 results, none of which is related to previous fracture. In the neurosurgery
      literature, however, there is a case report of a pathological fracture of the
      odontoid related to PVNS.

PMID- 30211353
TI  - Surgical Wound Classification and Surgical Site Infections in the Orthopaedic
      Patient.
AB  - Introduction: The Centers for Disease Control and Prevention created a surgical
      wound classification system (SWC: I, clean; II, clean/contaminated; III,
      contaminated; and IV, dirty) to preemptively identify patients at risk of
      surgical site infection (SSI). The validity of this system is yet to be
      demonstrated in orthopaedic surgery. We hypothesize a poor association between
      the SWC and the rate of subsequent SSI in orthopaedic trauma cases. Methods: Nine
      hundred fifty-six orthopaedic cases were reviewed. Wounds were risk stratified
      intraoperatively using the SWC grades (I-IV). SSI was diagnosed clinically or
      with objective markers. The SWC was compared with SSI rates using a Fisher exact
      test. Significance was set at P < 0.05. Results: Four hundred patients met the
      selection criteria. The rate of infection was not significantly different across
      the SWC grades (P = 0.270). There was a significantly higher risk of SSI among
      patients with diabetes (P = 0.028). Conclusions: The Centers for Disease Control
      and Prevention SWC showed poor utility in predicting and risk stratifying
      postoperative SSIs in orthopaedic surgical cases.

PMID- 30211354
TI  - Malpositioning of Prosthesis: Patient-specific Total Knee Arthroplasty Versus
      Standard Off-the-Shelf Total Knee Arthroplasty.
AB  - Introduction: A recent study has challenged the premise that a patient-specific
      (PS)-designed total knee arthroplasty (TKA) component has better clinical
      survival than an off-the-shelf (OTS) prosthesis. Methods: We developed the finite
      element models for PS TKA and OTS TKA with 5 degrees  varus and valgus
      malalignment and 5 degrees  internal and external malrotations. Results: Contact
      stress on the medial side of the insert increased with internal femoral
      malrotation and varus tibial malalignment, but it decreased with external femoral
      malrotation and varus tibial malalignment in both PS TKA and OTS TKA. An increase
      in ligament force occurred in valgus malalignment and external malrotation, and
      in particular, the force exerted on the medial collateral ligament increased.
      However, PS TKA provided better biomechanical effects than did the standard OTS
      TKA with malpositioning in TKA. Discussion: These results emphasize the
      importance of precise surgical preservation in regard to the TKA position.

PMID- 30211356
TI  - Incidence, Positional Distribution, Severity, and Time Missed in Medial
      Collateral Ligament Injuries of the Knee in NCAA Division I Football Athletes.
AB  - Introduction: We studied injury to the medial collateral ligament (MCL) in
      National Collegiate Athletic Association (NCAA) Division I football players,
      their incidence, magnitude of injury, distribution by position, and missed time,
      which has not previously been described in a consecutive series. Methods: The
      knee injuries sustained in 163 consecutive NCAA Division I collegiate football
      players at our institution were evaluated over a span of 6 years. Results: The
      incidence of MCL injuries with any knee injury was 29% (47 of 163). Of 47 MCL
      injuries, 34% occurred in defensive linemen and 29% in offensive linemen. The
      average days missed by linemen were 14.65 compared with 4.5 by nonlinemen (P =
      0.07). The MCL injuries in linemen were more severe than nonlinemen (0.018).
      Discussion: MCL injuries occur most commonly in linemen in whom the magnitude of
      injury is also more significant than nonlinemen. Linemen miss more days than do
      nonlinemen to MCL injury. Study Design: Descriptive Epidemiology Study.

PMID- 30211355
TI  - A Systematic Review of Outcome Measures Assessing Disability Following Upper
      Extremity Trauma.
AB  - Objectives: To define upper extremity outcome measures focusing on trauma and
      level of initial psychometric evaluation and to assess methodological quality of
      relevant patient-reported outcome (PRO) measures. Data Sources: A broad search
      strategy using PubMed, OVID, CINAHL, and PsycINFO was deployed and reported using
      PRISMA (PROSPERO: CRD42016046243). Study Selection Extraction Synthesis: PRO
      measures involving orthopedic trauma in their original development were selected
      and original publications assessed, including psychometric evaluations.
      Extraction, synthesis, and quality assessment were performed using COSMIN.
      Results: Of 144 upper extremity outcome measures, the majority were designed for
      the shoulder, wrist, and hand; 20% (n = 29/144) involved trauma conditions in
      their initial development, PRO measurements, and psychometric evaluation on
      introduction. Methodological quality was highly variable. Conclusion: A few PRO
      measures were originally designed for use in upper extremity trauma.
      Methodological quality and psychometric evaluation need to improve. This review
      aims to highlight strengths and weaknesses and guide decision making in this
      field.

PMID- 30211357
TI  - Lyme Disease: A Potential Source for Culture-negative Prosthetic Joint Infection.
AB  - The presentation of Lyme arthritis can mimic periprosthetic joint infection (PJI)
      caused by typical bacterial organisms. A patient with left total knee
      arthroplasty (TKA) and chronic Lyme disease presented to our institution with
      Lyme-associated PJI. He complained of pain, erythema, and fever for 3 days and
      met Musculoskeletal Infection Society criteria for PJI. Preoperative synovial
      fluid Lyme polymerase chain reaction (PCR) and serological tests were positive,
      whereas both preoperative aspiration and intraoperative cultures were negative.
      The patient underwent resection arthroplasty with insertion of an antibiotic
      spacer followed by intravenous ceftriaxone and oral doxycycline treatment for 6
      weeks. He underwent reimplantation at 8 weeks after repeat synovial fluid PCR
      analysis was negative. At 1 year, the patient was asymptomatic with a painless,
      functional, revision TKA. It is essential to consider Lyme-associated PJI in the
      setting of culture-negative PJI, especially in regions with a high prevalence of
      Lyme disease.

PMID- 30211358
TI  - Perioperative Factors Affecting the Length of Hospitalization After Shoulder
      Arthroplasty.
AB  - Objective: To determine factors related to length of hospitalization after
      shoulder arthroplasty. Methods: A retrospective review identified patients who
      underwent shoulder arthroplasty between 2009 and 2012 at our institution. Factors
      were evaluated for their association with hospitalization length in a univariate
      model. Diagnoses were categorized into four groups: (1) osteoarthritis, cuff tear
      arthropathy, massive rotator cuff tear, or osteonecrosis; (2) acute fracture or
      fracture sequelae; (3) inflammatory arthropathy; and (4) failed shoulder
      arthroplasty. Significant factors were then evaluated using a multivariate model.
      Results: Four hundred twenty-five shoulder arthroplasties were identified
      (average age, 66.9 years). Arthroplasty type significantly affected
      hospitalization length. Significant factors for increased hospitalization using
      multivariate analysis were diabetes mellitus, American Society of
      Anesthesiologists score of 3 or 4, acute fracture or fracture sequelae diagnosis,
      inflammatory arthropathy, and a blood transfusion. Discussion: Independent
      factors using multivariate analysis are diabetes, an American Society of
      Anesthesiologists score >=3, fracture or fracture sequelae, inflammatory
      arthritis, and a perioperative blood transfusion. Level of Evidence: Level III
      therapeutic study.

PMID- 30211359
TI  - Is It Time We Changed How We Measure Length of Stay for Hip and Knee
      Arthroplasty?
AB  - Introduction: Patient length of stay (LOS) for lower limb arthroplasty is a
      frequently quoted outcome measure. However, the use of mean values in days is
      prone to being skewed by outliers. Methods: Between January 2013 and December
      2015, patient LOS for primary hip and knee replacement was collected in 1,168
      patients. There were two groups: pre- and postinstitution of the Rapid Recovery
      Program. The hypothesis was that reducing LOS would highlight proportionate
      differences when using hours as the measuring unit. Results: Statistical analysis
      confirmed a significant reduction in LOS between the Enhanced Recovery Program
      and Rapid Recovery Program (P < 0.001). Discussion: Use of the median LOS reduces
      the impact of outliers. Use of hours as the unit of measure of LOS enabled
      analysis of the time of day of discharge. With decreasing LOS and day-case
      arthroplasty, a measurement in median hours should become the standard to allow
      for the detection of subtle changes.

PMID- 30211360
TI  - Development of Postoperative Spinal Arteriovenous Fistula After Lumbar
      Laminectomy, Decompression, and Posterior Spinal Fusion.
AB  - Spinal dural arteriovenous fistulas are a rare cause of low back pain, bilateral
      lower extremity weakness, or pain with sensory changes. They are typically found
      in males in the fifth and sixth decades of life, associated with a progressive
      decline in symptoms that make initial diagnosis challenging in some patients. We
      present a case report and literature review of an 80-year-old woman with a long
      standing history of progressively worsening back pain and lower extremity pain
      that has limited her daily activities. When preoperative MRI of the lumbar spine
      showed high-grade stenosis and listhesis of L4-L5, the patient was taken to the
      operating room for an L4-L5 laminectomy, decompression, facetecomy, and
      instrumented fusion. Her postoperative course did not show improvement of
      symptoms, which in fact worsened, leading to gait imbalance and instability.
      Postoperative MRIs of the patient were concerning for a spinal dural
      arteriovenous fistula, which was confirmed and treated by spinal angiography and
      embolization.

PMID- 30211361
TI  - Use of a Silver Nylon Dressing Following Total Hip and Knee Arthroplasty
      Decreases the Postoperative Infection Rate.
AB  - Introduction: Prosthetic joint infection (PJI) is a potentially catastrophic
      complication of total joint replacement. Our purpose was to determine whether the
      use of a silver dressing reduces the incidence of superficial and deep PJI
      following primary total hip replacement and total knee replacement. Methods: A
      case-control study of primary total hip replacement and total knee replacement
      was performed to compare the incidence of superficial and deep PJI in patients
      who received a silver nylon dressing with patients who received a standard
      dressing. Results: The incidence of infection was significantly lower in the
      study group compared with the control group. There were no deep PJIs in the
      silver dressing group. Twelve patients (2.3%) in the control group developed PJI.
      Discussion: The use of a silver dressing significantly reduced the incidence of
      superficial and deep PJI following total joint replacement (P = 0.010). Given the
      financial impact of PJI, the application of silver dressings may result in
      considerable cost savings, and a formal cost-benefit analysis could be
      investigated.

PMID- 30211363
TI  - Anterior Surgical Treatment of Scoliosis in a Patient With Loeys-Dietz Syndrome.
AB  - Loeys-Dietz syndrome (LDS) is an autosomal dominant disorder affecting the
      connective tissue, resulting in laxity, and can be challenging if surgical
      treatment is needed. Literature concerning scoliosis and its treatment in LDS is
      limited. This is a report of scoliosis surgery in a 12-year-old girl with LDS.
      She underwent anterior instrumented spinal fusion of the segments T12 to L3
      because of a left-sided thoracolumbar scoliosis of 42 degrees  with dysplastic
      pedicles. The scoliosis was reduced by 40%, from 42 degrees  to 25 degrees ,
      resulting in a satisfactory clinical outcome with a minimal amount of surgical
      invasion and lack of complications. A minimal approach and anterior instrumented
      spinal fusion surgery can be considered a valuable surgical treatment alternative
      for scoliosis in patients with LDS, avoiding the placement of pedicle screws in
      dysplastic pedicles and using the abnormal laxity of the connective tissue as an
      advantage.

PMID- 30211362
TI  - Multimodal Neuromonitoring During Safe Surgical Dislocation of the Hip for Joint
      Preservation: Feasibility, Safety, and Intraoperative Observations.
AB  - Introduction: Nerve injuries can occur from major hip surgeries, and some may be
      significant. Our goal was to assess the feasibility and safety of neuromonitoring
      during hip preservation surgery and the incidence of alerting events during such
      monitoring. Methods: Twenty-five adult patients underwent surgical hip
      dislocation for femoroacetabular impingement. Upper and lower extremity
      somatosensory evoked potentials, lower extremity transcranial motor evoked
      potentials, and lower extremity electromyography were recorded. Results: We
      observed a temporary reduction of the monitored parameters in twelve patients
      (48%) during surgery. There were no clinically significant neurological deficits
      postoperatively in any cases. Discussion: Neuromonitoring did demonstrate events
      during hip surgery in our case series. Although it may not be practical to use
      neuromonitoring in all major hip surgeries, it may be prudent from the
      perspective of patient safety to use it in high-risk cases, including those
      requiring prolonged surgical time; in patients with high body mass index,
      excessive deformity correction, and preexisting neuropathy; and in revision
      cases, among others.

PMID- 30211364
TI  - Giant Cell Tumor of Distal Radius After Open Reduction Internal Fixation for
      Distal Radius Fracture.
AB  - Case: A 77-year-old woman presented with volar wrist pain 1.5 years after
      undergoing distal radius volar locked plating for fracture. Radiographs and CT
      were notable only for plate prominence, and she was admitted for removal of
      hardware. Intraoperatively, a large cavitary bone lesion was found.
      Histopathology demonstrated a giant cell tumor of the bone. Definitive management
      consisted of wide en bloc resection and osteoarticular allograft reconstruction,
      which achieved local control and an acceptable clinical result. Conclusion:
      Although not previously described, a giant cell tumor of the bone may develop
      after fracture. Metal artifact in an area of previous internal fixation can make
      recognition challenging, but dual-energy CT can be used to decrease this
      artifact. Local control can be achieved with wide excision and reconstruction.

PMID- 30211365
TI  - Pediatric and Adolescent T-type Distal Humerus Fractures.
AB  - Although fractures of the elbow are extremely common in pediatric patients, the T
      type distal humerus fracture is rare and offers unique challenges. The mechanism
      of injury may be similar to the adult counterpart and is usually caused by a fall
      onto a flexed elbow or from a direct blow. Diagnosing these injuries may be
      difficult. They often resemble extension-type supracondylar fractures, yet the
      treatment algorithm is quite different. In younger patients, percutaneous pinning
      remains a viable option, but for older adolescents, open reduction and internal
      fixation provides stable fixation at the elbow and the most reliable restoration
      of the articular surface. Appropriate imaging, careful radiographic diagnosis,
      and choice of surgical technique are of paramount importance when treating young
      patients with this injury. Most pediatric and adolescent patients with T-type
      distal humerus fractures have results better than those of adults but often worse
      than other elbow fractures in this age group.

PMID- 30211367
TI  - Posterior Humeral Circumflex Artery Aneurysms in Two Collegiate Pitchers.
AB  - : Posterior humeral circumflex artery aneurysms in upper extremity athletes are a
      rarely described entity now beginning to gain wider recognition in the medical
      literature. Recent studies have demonstrated that these aneurysms may be
      underdiagnosed and that appropriate recognition with early diagnosis is
      imperative for improved outcomes. This case report aims to increase awareness of
      posterior humeral circumflex artery aneurysms and to educate physicians on the
      appropriate recognition of symptoms, diagnosis, and treatment. We describe two
      presentations of the same injury, as well as an approach to diagnosis and
      treatment. We also discuss new diagnostic techniques and future research plans.
      Level of Evidence: Level III diagnostic study.

PMID- 30211366
TI  - Comparison of Open Reduction and Internal Fixation Versus Closed Reduction and
      Percutaneous Fixation for Medial Malleolus Fractures.
AB  - Introduction: Surgical treatment of medial malleolus (MM) fractures can be
      performed through open or percutaneous approaches, although comparisons between
      these two approaches have not been undertaken. In this study, we compared
      patients with MM fractures treated with closed reduction and percutaneous
      fixation (CRPF) with patients treated with traditional open reduction and
      internal fixation (ORIF). Methods: A group of 165 consecutive patients underwent
      surgical fixation of a closed MM fracture from 2011 to 2015 at a single
      institution. Thirty-one underwent CRPF and 134 underwent ORIF. Patient
      demographics, injury characteristics, treatment methods, and outcome variables
      were recorded through review of patient charts, radiographs, and surgical
      reports. Results: The rate of MM fracture comminution was higher in the ORIF
      group compared with the CRPF group (9.7% vs 27.6%; P = 0.04). All other patient
      and injury variables were similar between the two groups. There was no
      statistically significant difference observed between the CRPF and ORIF groups
      regarding outcomes, including nonunion, malunion, time to union, rate of hardware
      removal, and wound complications. Discussion: Both CRPF and ORIF resulted in
      acceptable radiographic outcomes and low complication rates for the treatment of
      MM fractures.

PMID- 30211368
TI  - Traumatic Orthopaedic Injury Is Not an Independent Risk Factor for High
      Postdischarge Opioid Consumption.
AB  - Introduction: The purpose of this study was to quantify how opioid use in
      patients with traumatic injury compared with opioid use in patients undergoing
      elective arthroplasty. Methods: In a retrospective review, 235 adult trauma
      patients treated surgically for fracture were compared with 98 patients
      undergoing elective total hip or knee arthroplasty. Inpatient, discharge, and
      postdischarge opioid use were recorded in oral morphine equivalents (OMEs).
      Results: There were no differences between trauma and elective arthroplasty
      patients for inpatient opioid use (OME/day: 70.2 vs. 67.3; P = 0.53), discharge
      prescription (OME: 542 vs. 594; P = 0.13), or postdischarge opioid use (OME: 986
      vs. 1,147; P = 0.29). Postdischarge opioid use was positively correlated with
      Caucasian race, intensive care unit admission, baseline alcohol or opioid use,
      and higher discharge prescriptions (P < 0.0001; adjusted R2 = 0.127). Discharge
      prescription amount was the most significant predictor. Discussion: Traumatic
      injury is not a predictor of high post-discharge opioid use. Demographic, social,
      and physician prescribing behaviors contribute to higher postdischarge opioid
      consumption.

PMID- 30211369
TI  - Overlooked Hoffa Fracture in a Patient With Neurofibromatosis-1.
AB  - Hoffa fractures are rare fractures of either one or both femoral condyles in the
      coronal plane. They usually occur as a result of high-velocity, high-energy
      trauma with axial compression of the lower limb and a typically flexed position
      of the knee. The lateral condyle is affected more frequently. Diagnosis of a
      coronal fracture is often missed in conventional radiography, so additional CTs
      of the knee are highly recommended in unclear cases. Because of permanent
      shearing forces, fracture healing is unlikely without surgical treatment. In the
      case we present here, the Hoffa fracture occurred after minimal trauma and was
      associated with an ipsilateral patellar dislocation and a meniscal tear. The
      fracture was initially overlooked. Bone quality was affected by a preexisting
      neurofibromatosis-1 condition.

PMID- 30211370
TI  - A Novel Cadaveric Model of the Quadriga Effect.
AB  - Introduction: The quadriga phenomenon results from excessive shortening of the
      flexor digitorum profundus (FDP) tendon to the middle, ring, or small finger.
      Methods: Five cadaveric specimens were used to create a model for quadriga. The
      FDP tendons to the middle, ring, and small fingers were shortened in 5-mm
      increments, and the tip-to-palm (TTP) distance of adjacent fingers was recorded.
      Results: Shortening of the middle finger FDP by 10 mm resulted in an average TTP
      distance of 6 mm in the ring finger and 5 mm in the small finger. Shortening the
      ring finger FDP by 10 mm produced an average TTP distance of 11 mm in the middle
      finger and 9 mm in the small finger. Shortening of the small finger FDP by 10 mm
      resulted in an average TTP distance of 14 mm in the middle finger and 10 mm in
      the ring finger. Discussion: Shortening the FDP by as little as 10 mm produced a
      significant quadriga effect, which was more pronounced with shortening of the
      small and ring FDP tendons compared to the middle finger.

PMID- 30211372
TI  - Oblique Inguinal Incision in Bernese Periacetabular Osteotomy: Surgical
      Technique.
AB  - Objective: To present a modification in the technique of an anterior approach for
      Bernese periacetabular osteotomy through an oblique inguinal incision.
      Introduction: Reorientation of the acetabulum in Bernese periacetabular osteotomy
      provides adequate coverage of the femoral head, improving biomechanical
      conditions of the joint without the risk of osteonecrosis. The principal author
      modified this procedure through an anterior approach with no detachment of the
      rectus femoris, allowing early rehabilitation. Evolution of scars is an issue
      both in the original technique and in our modification in terms of hypertrophy,
      depression, or hyperpigmentation and dehiscence. We introduce an oblique inguinal
      incision reducing both static and dynamic tension of the skin, allowing healing
      and avoiding development of unsatisfactory scars. Methods: Thirty-five surgeries
      with a modified technique were performed in 27 patients between 2014 and 2016.
      The average patient age was 27.09 years. No patients were excluded. Development
      of hypertrophic, depressed, and hyperpigmented scars was evaluated in addition to
      dehiscence. Results: The average length of the scar was 14.1 cm, and average
      diastasis was 1.3 mm. There were no hypertrophic, depressed, or hyperpigmented
      scars. No patients had dehiscence or resutures of surgical wounds. Conclusion:
      Oblique inguinal incision for the anterior approach in Bernese periacetabular
      osteotomy is a technique that allows healing of surgical wounds without
      dehiscence or hypertrophic changes by respecting tension lines. It has a high
      rate of patient satisfaction, with no complications.

PMID- 30211373
TI  - Acute Carpal Tunnel Syndrome After Canine Bite.
AB  - Acute carpal tunnel syndrome (ACTS) from an infected source is rare because most
      cases result from trauma. There are cases of ACTS occurring after feline bites,
      but none in the reported literature after canine bites. The following is a case
      report of a 58-year-old woman who presented to the emergency department with
      progressive median nerve symptoms after a canine bite. In the operating room, a
      significant mass effect was found within the contents of the carpal tunnel
      secondary to an abundance of purulence. The patient was treated urgently with
      irrigation and debridement of the wrist with an extended open carpal tunnel
      release and flexor tenosynovectomy and discharged with peripheral venous access
      for long-term antibiotics. At 1-month follow-up, the healed wound showed no signs
      of infection. A mild sensory deficit remained in the median nerve distribution.

PMID- 30211371
TI  - Concussions in NCAA Varsity Football Athletes: A Qualitative Investigation of
      Player Perception and Return to Sport.
AB  - Background: The objective of this study was to understand the experiences and
      perspectives of varsity football athletes on return to play following a
      concussion injury. Methods: Two experienced interviewers conducted qualitative,
      semistructured interviews of college-level football players who had sustained at
      least one concussion during their varsity careers. Results: Twenty varsity
      football players who averaged 2.3 concussions each (range, 1-5) were interviewed
      regarding peer pressure, the culture of football, and player awareness as factors
      affecting return to sport following a concussion. Less common secondary factors
      included risk management, severity and timing of the injury, and team support.
      Conclusions: Psychological stressors, the culture of football, and increased
      awareness were the most influential factors affecting collegiate football
      players' deciding to return to sport following a concussion. Level of Evidence:
      Level III.

PMID- 30211374
TI  - Iliopsoas Abscess Presenting With Sacral Fracture and Gluteal Abscess: A Clinical
      Conundrum.
AB  - Abscess of the iliopsoas muscle is a rare condition that requires a high degree
      of clinical suspicion for diagnosis. High mortality rates highlight the need for
      prompt recognition. We report the case of a 26-year-old man, with a history of
      intravenous drug use, who was referred from an outside facility with sacral
      fracture and gluteal abscess. Sacral trauma occurred 3 weeks before presentation,
      with progressive worsening of buttock pain. The patient was treated with
      irrigation and debridement of the gluteal abscess. Follow-up MRI revealed a
      communicating iliopsoas abscess that initially had been undiagnosed. After a
      prolonged hospital stay requiring additional irrigation and debridement
      procedures, the patient was discharged in a stable condition. Five-month follow
      up has demonstrated no evidence of recurrence of infection. To our knowledge,
      this is the first reported case of Staphylococcus aureus gluteal abscess with
      pelvic extension into the iliopsoas secondary to sacral trauma and intravenous
      drug use.

PMID- 30211375
TI  - Safety of Outpatient Shoulder Surgery at a Freestanding Ambulatory Surgery Center
      in Patients Aged 65 Years and Older: A Review of 640 Cases.
AB  - Introduction: With increasing utilization of surgery centers, it is important to
      demonstrate the safety of outpatient shoulder surgery in freestanding ambulatory
      surgery centers. No studies have specifically looked at the Medicare-age
      population and the rate of outpatient shoulder procedure complications in these
      patients at an ambulatory surgery center. Methods: Six hundred forty patients
      were included in our study between 2000 and 2015. The incidence of major
      complications was identified, including acute infection requiring intravenous
      antibiotics or irrigation and debridement, postoperative transfer to a hospital,
      wrong-site surgical procedures, retention of a foreign object, postoperative
      symptomatic thromboembolism, medication errors, and bleeding/wound complications.
      Results: There was a total of seven occurrence reports in seven patients, for a
      reported adverse event rate of 1.01%. Conclusions: Our findings are consistent
      with currently reported outpatient hospital-based data and illustrate the safety
      of outpatient shoulder procedures at a freestanding ambulatory surgery center in
      Medicare-age patients.

PMID- 30211376
TI  - Off the Market: The Percentage of Products Available After Ten Years.
AB  - Background: We observed that medical devices advertised in journals are often no
      longer available 5 to 10 years after first being advertised. In this study, we
      quantified the percentage of products advertised from 2003 to 2008 in the Journal
      of Bone and Joint Surgery, American, which were still available 5 to 10 years
      after first being advertised. Methods: We created a database of 427 unique
      orthopaedic products advertised in the Journal of Bone and Joint Surgery. In
      2013, we classified products into categories: available in advertised form,
      available in modified form, available under a different manufacturer, and
      available but temporarily recalled, discontinued voluntarily, or discontinued by
      forced recall. Results: A total of 13.8% of products were discontinued 5 to 10
      years after being advertised. Three percent were discontinued through forced
      recall, and 10.8% were discontinued voluntarily. Of the products still available,
      60.2% were in current form, 12.9% were modified, 11.9% were available under a
      different company, and 1.2% were available but were temporarily recalled.
      Conclusion: Five to 10 years after the initial advertisement, nearly 40% of
      products were not available in their original advertised form.

PMID- 30211377
TI  - Knee Arthrodesis Outcomes After Infected Total Knee Arthroplasty and Failure of
      Two-stage Revision With an Antibiotic Cement Spacer.
AB  - Background: Reinfected total knee arthroplasty can be managed with a second two
      stage exchange or a knee arthrodesis procedure. Methods: Twenty-three patients
      with knee arthrodesis after failed exchange arthroplasty for infection were
      reviewed. Patients were managed with a staged protocol of implant extraction,
      debridement, and implantation of an antibiotic spacer, with subsequent
      arthrodesis. Follow-up averaged 40.4 months, with a minimum of 1 year. Results:
      Bony union with eradication of infection was achieved in 20/23 knees. Sixteen of
      the 20 patients were able to ambulate with minimal pain. The average time to
      union was 11.3 months, and the average leg length discrepancy was 4.85 cm. The
      average Knee Society Score after arthrodesis was 44, and the average visual
      analog scale pain score was 1.73. Three patients underwent above-knee amputation.
      Discussion: Knee arthrodesis performed for persistent periprosthetic infection
      allowed for eradication of infection and union in 87% of the patients, creating a
      stable knee fusion.

PMID- 30211378
TI  - Transfer Time After Acceptance to a Level I Trauma Center.
AB  - Background: Timely treatment of pediatric orthopaedic emergencies at level I
      trauma centers is frequently dependent on transfers from neighboring centers.
      Methods: Records were collected from our level I trauma center for patients with
      isolated orthopaedic issues accepted for transfer in 2015. Open fractures,
      compartment syndrome, septic arthritis, and supracondylar humerus fractures with
      ecchymosis or neurovascular compromise were emergent. The rush hour was 6 am to
      10 am and 3 pm to 7 pm. Results: Ninety-six patients met the inclusion criteria;
      19% (18/96) were orthopaedic emergencies and 37% (35/96) occurred during the rush
      hour. The average time from transfer acceptance to accepting hospital admission
      was 203 minutes (range, 68 to 584 minutes; SD, 85.8 minutes). The average time
      from transfer acceptance to departure from the transferring facility was 114
      minutes (range, 7 to 391 minutes; SD, 71.9 minutes). There was no correlation
      between the transfer time and rush hour (P = 0.40), emergent versus nonemergent
      (P = 0.42), or routed distance from the hospital (P = 0.46). Conclusion: The
      average transfer time exceeded 3 hours and was independent of the distance, the
      rush hour, or urgency of patient condition. An average 2-hour delay was
      encountered for patients while leaving a medical facility after acceptance of
      transfer.

PMID- 30211380
TI  - Readability of Sports Injury and Prevention Patient Education Materials From the
      American Academy of Orthopaedic Surgeons Website.
AB  - Introduction: The purpose of this study is to evaluate the readability of 114
      Sports Injury and Prevention patient education materials provided by the American
      Academy of Orthopaedic Surgeons (AAOS). Methods: We evaluated all articles
      written in English posted under the Sports Injury and Prevention section of the
      AAOS website using readability software to compute six readability scores, which
      we compared with the eighth-grade level using a two-tailed one-sample Student t
      test. Results: The mean reading grade level calculated by each readability test
      was markedly higher than the eighth-grade level. We reported mean +/- SD for each
      test: Flesch-Kincaid grade level (8.95 +/- 1.51; P < 0.001), Simple Measure of
      Gobbledygook (11.53 +/- 1.18; P < 0.001), Coleman-Liau index (11.16 +/- 1.33; P <
      0.001), Gunning Fog index (11.06 +/- 1.63; P < 0.001), New Dale-Chall (9.49 +/-
      1.66; P < 0.001), and FORCAST formulas (10.96 +/- 0.60; P < 0.001). Discussion:
      This study shows that patient education materials provided by the AAOS concerning
      sports injury and prevention are written at a readability level too high for
      patients to understand. On average, patient materials are written at least 2.5
      grade levels higher than national recommendations. Only 7% of the 114 articles
      had readability scores in line with national recommendations. These findings
      indicate a need for revised patient education materials geared toward bringing
      the readability level down to the recommended eighth-grade level.

PMID- 30211379
TI  - Clinical and Functional Outcomes: Primary Constrained Condylar Knee Arthroplasty
      Compared With Posterior Stabilized Knee Arthroplasty.
AB  - Introduction: Constrained condylar knee (CCK) prostheses are commonly used in
      difficult primary total knee arthroplasty and revision total knee arthroplasty.
      We postulate that the use of CCK prostheses in primary knee arthroplasty may
      result in decreased range of motion but with better patient-reported functional
      scores compared with primary posterior stabilized (PS) knee prostheses because of
      increased varus and valgus stability from increased constraint. Methods: We
      conducted a case-control study using prospectively collected data on functional
      outcome scores and range of motion preoperatively and at 6 months and at 2 years.
      Thirty-eight patients with primary CCK arthroplasty were matched with 38 patients
      with primary PS knee arthroplasty treated by a single surgeon. Institutional
      review board approval was obtained. Analysis was done using the independent t
      test. Results: Total 76 patients with 61 (80.3%) female patients, 30 (39.5%) left
      knees, and 9 (11.8%) valgus knees. There was no significant difference in
      preoperative age (CCK arthroplasty 70.7 +/- 6.0 years versus PS knee arthroplasty
      68.5 +/- 5.2 years; P < 0.085), body mass index (27.2 +/- 4.4 versus 26.3 +/-
      5.2; P < 0.44), Oxford Knee Score (35.8 +/- 7.8 versus 36.0 +/- 7.6; P < 0.92),
      and Medical Outcomes Study 12-Item Short Form (SF-36) scores and knee extension
      (8.0 degrees  +/- 6.7 degrees  versus 7.7 degrees  +/- 7.6 degrees ; P < 0.84).
      There was no significant difference in preoperative knee flexion (106.0 degrees 
      +/- 22.9 degrees  versus 117.3 degrees  +/- 20.1 degrees ; P < 0.026). There was
      no significant difference in 6-month knee extension (4.5 degrees  +/- 6.8 degrees
      versus 4.1 degrees  +/- 4.5 degrees ; P < 0.80), knee flexion (110.5 degrees  +/
      15.8 degrees  versus 110.9 degrees  +/- 15.5 degrees ; P < 0.92), Oxford Knee
      Score (18.9 degrees  +/- 3.4 degrees  versus 20.1 degrees  +/- 5.3 degrees ; P <
      0.27), and SF-36 scores. There was no significant difference in 2-year knee
      extension (1.8 degrees  +/- 5.7 degrees  versus 1.5 degrees  +/- 4.0 degrees ; P
      < 0.82), knee flexion (111.3 degrees  +/- 13.6 degrees  versus 115.0 degrees  +/-
      16.5 degrees ; P < 0.30), Oxford Knee Score (18.5 degrees  +/- 3.7 degrees 
      versus 18.2 degrees  +/- 4.2 degrees ; P < 0.77), and SF-36 scores. Conclusion:
      The use of CCK prostheses in primary knee arthroplasty gives similar clinical and
      functional outcomes at 2 years as those of PS knee prostheses, despite increased
      constraint.

PMID- 30211381
TI  - Midfoot Degenerative Arthritis and Partial Fusion After Pediatric Lisfranc
      Fracture-Dislocation.
AB  - We present a case of a 10-year-old girl who sustained a Lisfranc fracture
      dislocation after an all-terrain vehicle accident. She underwent open reduction
      and internal fixation with smooth Kirschner wires. At 5-year follow-up, she had
      developed functional pain and radiographic evidence of degenerative arthritis and
      partial fusion of her midfoot. There are several possible explanations for this
      outcome, including loss of reduction, traumatic or iatrogenic physeal injury, and
      severity of initial injury. Long-term outcomes in children with Lisfranc injuries
      are not well described. Our case may begin to shed light on the natural history
      of these injuries in the pediatric population, with the consideration of
      potential treatment implications and pitfalls.

PMID- 30211382
TI  - Validation of Digital Visual Analog Scale Pain Scoring With a Traditional Paper
      based Visual Analog Scale in Adults.
AB  - Background: The visual analog scale (VAS) is a validated, subjective measure for
      acute and chronic pain. Scores are recorded by making a handwritten mark on a 10
      cm line that represents a continuum between "no pain" and "worst pain." Methods:
      One hundred consecutive patients aged >=18 years who presented with a chief
      complaint of pain were asked to record pain scores via a paper VAS and digitally
      via both the laptop computer and mobile phone. Ninety-eight subjects, 51 men
      (age, 44 +/- 16 years) and 47 women (age, 46 +/- 15 years), were included. A
      mixed-model analysis of covariance with the Bonferroni post hoc test was used to
      detect differences between the paper and digital VAS scores. A Bland-Altman
      analysis was used to test for instrument agreement between the platforms. The
      minimal clinically important difference was set at 1.4 cm (14% of total scale
      length) for detecting clinical relevance between the three VAS platforms. A
      paired one-tailed Student t-test was used to determine whether differences
      between the digital and paper measurement platforms exceeded 14% (P < 0.05).
      Results: A significant difference in scores was found between the mobile phone
      based (32.9% +/- 0.4%) and both the laptop computer- and paper-based platforms
      (31.0% +/- 0.4%, P < 0.01 for both). These differences were not clinically
      relevant (minimal clinically important difference <1.4 cm). No statistically
      significant difference was observed between the paper and laptop computer
      platforms. Measurement agreement was found between the paper- and laptop computer
      based platforms (mean difference, 0.0% +/- 0.5%; no proportional bias detected)
      but not between the paper- and mobile phone-based platforms (mean difference,
      1.9% +/- 0.5%; proportional bias detected). Conclusion: No clinically relevant
      difference exists between the traditional paper-based VAS assessment and VAS
      scores obtained from laptop computer- and mobile phone-based platforms.

PMID- 30211384
TI  - Rapid Complete Acetabular Destruction in Metal-on-Metal Total Hip Arthroplasty.
AB  - Adverse local tissue reaction, osteolysis, and subsequent increased incidence of
      failure have been associated with metal-on-metal (MoM) total hip arthroplasty
      (THA). We present the case of a 68-year-old woman with rheumatoid arthritis who
      has undergone left THA with a MoM bearing. Seven years postoperatively, she
      presented with 6 weeks of severe left hip pain. Sequential radiographs and
      advanced imaging demonstrated a rapid onset of extensive acetabular osteolysis
      with pelvic discontinuity and pseudotumor formation. She underwent revision THA
      using a cup-cage construct with a satisfactory outcome. In this article, we
      review current evidence-based management options for pelvic discontinuity, as
      well as other complications related to MoM THA.

PMID- 30211383
TI  - Systematic Review of Tendon Transfer Versus Nerve Transfer for the Restoration of
      Wrist Extension in Isolated Traumatic Radial Nerve Palsy.
AB  - Purpose: To compare the outcomes of tendon transfer and nerve transfer for radial
      nerve palsy. Methods: We performed a systematic review of the literature in
      EMBASE, PubMed, and Cochrane Database to include studies that address persistent
      traumatic radial nerve palsy treated with tendon transfer or nerve transfer
      surgery. Results: We identified 2,044 citations; 1,512 texts were excluded
      because of content, and 96 texts were screened for eligibility. Texts were
      excluded if they did not report the motor score (M0 to M5 as determined by the
      British Medical Research Council) or measurements of range of motion of the
      wrist. Sixteen texts were eligible for qualitative synthesis. Outcomes of these
      studies show heterogeneity with regard to the technique and functional
      restoration. Conclusions: On the basis of the results of this systematic review,
      there does not seem to be a clearly superior technique; rather, there are
      advantages and disadvantages to each. Patient selection and surgeon experience
      are important when considering surgical interventions in this challenging
      clinical scenario. Nerve transfer surgery is an emerging technique that may offer
      patients meaningful functional gains with reduced donor site morbidity. Level of
      Evidence: Level III.

PMID- 30211385
TI  - Augmented Reality Visualization-guided Microscopic Spine Surgery: Transvertebral
      Anterior Cervical Foraminotomy and Posterior Foraminotomy.
AB  - Objective: We describe intraoperative augmented reality (AR) imaging to obtain a
      microscopic view in spine keyhole surgery. Background: Minimally invasive keyhole
      surgery has been developed even for spine surgery, including transvertebral
      anterior cervical foraminotomy and posterior cervical laminoforaminotomy. These
      methods are complex and require a skillful technique. Therefore, inexperienced
      surgeons hesitate to perform keyhole surgeries. The technology used in surgery is
      rapidly advancing, including intraoperative imaging devices that have enabled AR
      imaging and facilitated complicated surgeries in many fields. However, data are
      not currently available on the use of AR imaging in spine surgery. The purpose of
      this article was to introduce the utility of AR for spine surgery. Methods: We
      performed O-arm intraoperative imaging to create an augmented imaging model in
      navigation systems. Navigation data were linked to a microscope to merge the live
      view and AR. Augmented reality imaging shows the model plan in the real-world
      surgical field. We used this novel method in patients who underwent both keyhole
      surgeries. Results: We successfully performed both surgeries using the AR
      visualization guide. Conclusions: The AR navigation system facilitates
      complicated keyhole surgeries in patients who undergo spine surgery. Study
      Design: Technical report.

PMID- 30211386
TI  - Focal Periphyseal Edema: Are We Overtreating Physiologic Adolescent Knee Pain?
AB  - The goals of this study were to (1) introduce the MRI phenomenon of focal
      periphyseal edema (FOPE) to the orthopaedic community and (2) describe
      characteristic features and clinical outcomes of a small series of adolescents
      with FOPE lesions about the knee. The inclusion criterion was the presence of
      activity-related knee pain and periphyseal edema on T2-weighted MRI. Exclusion
      criteria were skeletal maturity, history of traumatic knee injury, and the
      presence of other knee abnormalities. Participants completed the Short Form 10
      and Pediatric International Knee Documentation Committee (pedi-IKDC) outcome
      assessments. Four patients (average age, 13.7 years) with atraumatic activity
      related knee pain and FOPE lesions were retrospectively identified. At follow-up
      (average, 15.8 months), all patients reported the ability to participate in
      physical activities at the desired level. The mean pedi-IKDC score was 71.2. With
      supportive treatment, patients with FOPE were able to return to sport, although
      they had lower-than-average outcome scores. Increased awareness and understanding
      of this clinical entity are necessary for provision of effective, cost-efficient
      care to patients with FOPE.

PMID- 30211387
TI  - Acute Paravertebral Compartment Syndrome: Follow-up and Literature Review.
AB  - Objective: To report on a patient with acute paravertebral and posterior thigh
      compartment syndrome after vigorous exercise. Background: Paravertebral
      compartment syndrome (PCS) is a rare clinical entity, typically occurring in male
      athletes after heavy exertion and weightlifting. Case: A 25-year-old man
      presented with back pain and hematuria hours after back-specific weightlifting.
      Clinical examination, laboratory markers, MRI, and elevated intracompartmental
      pressure measurements supported the diagnosis of bilateral paravertebral and
      posterior thigh compartment syndrome. The patient underwent paravertebral
      decompression via the Wiltse approach with immediate postoperative relief. He is
      doing well at 1 year, with recovery of lumbar extension strength, although MRI
      demonstrates moderate fatty replacement of paravertebral musculature.
      Conclusions: Although rare, early recognition of PCS and timely decompression can
      limit myonecrosis. Paravertebral compartment syndrome should be considered in the
      differential for athletic individuals with acute onset back pain. Study Design: A
      case report and review of literature.

PMID- 30211388
TI  - Comparative Outcomes Between the First and Second Operated Shoulders in Bilateral
      Shoulder Arthroplasty.
AB  - Introduction: Studies that report outcomes after staged bilateral shoulder
      arthroplasty (BSA) are limited. This study compared the overall improvement
      between the first and second operated shoulders after BSA. Methods: Preoperative
      and postoperative motion and patient-reported outcomes for function, pain, and
      general health were assessed for patients who underwent BSA with a 2-year follow
      up. Ultimate outcomes and the efficacy of treatment were compared between the
      first and second operated shoulders. Results: Seventy-three patients met the
      inclusion criteria (mean follow-up, 51.4 months). There were no notable
      differences between the first and second operated shoulders for all preoperative
      and postoperative variables except for the preoperative 12-item Short-Form
      Physical Component Score, which was greater in the second shoulder (P = 0.005).
      The efficacy of treatment was not markedly different except for the Physical
      Component Score (P = 0.001) and forward elevation (P = 0.01), which were greater
      after the first surgery. Discussion: Improvements in function, pain, and motion
      were not markedly different between the first and second shoulder arthroplasty
      surgeries.

PMID- 30211389
TI  - Flexor Tenosynovitis of the Hand Caused by Mycobacterium tuberculosis.
AB  - Infectious tenosynovitis of the hand is a serious condition with a high risk of
      morbidity. Mycobacterium tuberculosis is a rare cause of tenosynovitis,
      especially in regions where tuberculosis is no longer endemic, and presents
      significant diagnostic challenges. We present the case of a 42-year-old woman
      with no known history of or exposure to tuberculosis and a medical history of
      systemic lupus erythematosus on chronic immunosuppressive therapy who presented
      with swelling and erythema in the fifth finger of the left hand of 1-month
      duration. She underwent tenosynovectomy, and intraoperative cultures grew M
      tuberculosis. The patient completed an appropriate antibiotic regimen, and
      systemic workup revealed ring-enhancing lesions on brain MRI consistent with
      tuberculoma. We review the literature and current trends in the management of
      mycobacterial tenosynovitis, as well as the important teaching points of the
      case.

PMID- 30211390
TI  - Measurement of Intraoperative Blood Loss in Pediatric Orthopaedic Patients:
      Evaluation of a New Method.
AB  - Introduction: Our goal was to validate a new method of intraoperative blood loss
      measurement in pediatric patients who undergo orthopaedic surgery. Methods: We
      prospectively collected surgical sponges from 55 patients who underwent pediatric
      posterior spinal fusion, single-event multilevel surgery, or hip reconstruction
      for measurement of intraoperative blood loss. We enrolled patients if expected
      estimated blood loss (EBL) was >200 mL. The methods used for blood loss
      assessment included the Triton sponge scanning system, visual method, gravimetric
      method, and measured assay (reference) method. Results: The Triton system
      calculation of cumulative EBL per patient against the reference method yielded a
      strong positive linear correlation (R2 = 0.88). A weaker correlation was noted
      between the gravimetric method and reference EBL (R2 = 0.49). The Triton system
      had a low bias and narrow limits of agreement relative to the reference method
      (49 mL; 95% CI, 30 to 68). The gravimetric method had a higher bias and wider
      limits of agreement (101 mL; 95% CI, 67 to 135). The comparison of visual total
      EBL against the reference method yielded a notable discrepancy. Discussion:
      Estimated blood loss measured using the Triton system correlated better with the
      reference method than with the gravimetric method. The visual estimation method
      was found to be inaccurate. Intraoperative use of the Triton system is convenient
      and precise for monitoring intraoperative blood loss.

PMID- 30211391
TI  - Contamination of Irrigation Fluid During Primary Total Knee Arthroplasty.
AB  - Purpose: During surgical procedures, some amount of irrigation fluid leaks from
      the surgical site and accumulates on the sterile drapes. Whether these fluid
      collections show bacterial contamination over time in primary total knee
      arthroplasty remains unclear. Methods: In this study, we included 100 patients.
      We collected the samples of irrigation fluid before skin incision and every 30
      minutes after the start of surgery. In addition, at the end of surgery, we
      evaluated the suction tip for bacterial contamination. After 3 months, we
      clinically evaluated all patients for periprosthetic joint infection. Results:
      Although the drapes were found to be sterile after 30 minutes, fluid residues on
      the surgical drapes show a contamination rate of 22% after 60 minutes and thus a
      marked correlation between advanced duration of surgery and bacterial
      contamination. The suction tip was contaminated with bacteria in 22% of cases.
      The spectrum of pathogens typical of periprosthetic joint infection could be
      demonstrated. Conclusion: Fluid surgical drape reservoirs were abacterial during
      the first 30 minutes but showed marked bacterial contamination over time. For
      total knee arthroplasty, we recommend regular replacement of the suction tip
      every 30 minutes. In addition, irrigation fluid reservoirs should not be
      withdrawn by suction 30 minutes after skin incision.

PMID- 30211392
TI  - Irreducible Dislocation of the Radial Head Associated With Pediatric Monteggia
      Lesions.
AB  - Background: In pediatric patients with Monteggia lesions, the radial head can be
      reduced manually when displacement of the fractured ulna is corrected.
      Occasionally, however, a dislocated radial head could not be reduced manually
      even when the length and/or angulation of the fractured ulna had been corrected.
      We can find such cases in the literature, but those are single case reports. We
      encountered 17 cases of irreducible dislocation of the radial head in pediatric
      Monteggia lesions during the past 43 years. The purposes of this study were to
      identify the characteristics of our cases and to discuss the factors that
      inhibited reduction of the radial head. Methods: Of 109 children treated for
      Monteggia lesions between 1972 and 2015, we encountered 17 cases of irreducible
      dislocation of the radial head. The patients' ages averaged 7.1 years, ranging
      from 2.6 to 12.1 years. Directions of the radial head dislocation were anterior
      in five cases, anteromedial in four, lateral in one, and anterolateral in seven.
      Most of the patients were referred to us from local orthopaedic clinics because
      of irreducibility of the radial head. We reduced the radial head surgically and
      confirmed the causes of irreducibility. Results: In 10 of the 17 cases, the
      problem was identified as pseudoreduction. In those cases, the radial head was
      reduced in a supination position but redisplaced in a pronation position. Causes
      of irreducibility were traced to the annular ligament in 15 cases, biceps tendon
      in 1, and posterior interosseous nerve in 1. Conclusions: In cases of pediatric
      Monteggia lesions, we should pay attention to patients in whom the dislocated
      radial head is not reduced after closed reduction. The most frequent cause of
      hindered reduction was interposition of the annular ligament in the
      radiocapitellar joint. Here, the radial head seems to be reduced in the
      supination position but becomes redisplaced in the pronation position. After
      closed reduction, it is important to confirm whether the radial head is stable in
      both pronation and supination positions. Level of Evidence: Diagnostic level IV.

PMID- 30211393
TI  - Occipitocervical Dissociation in Three Siblings: A Pediatric Case Report and
      Review of the Literature.
AB  - This report includes three cases of occipitocervical (OC) dissociation in three
      siblings involved in a single, head-on, motor vehicle accident. The oldest
      sibling, a 9-year-old girl, required surgical fixation. The second sibling, a 6
      year-old boy, was treated nonsurgically with a neck brace. The youngest sibling,
      a 5-year-old boy, sustained a fatal OC dissociation. CT and MRI findings are used
      to assess the reliability of the currently recommended diagnostic modalities for
      OC dissociation. The literature review focuses on the diagnosis of OC
      dissociation via CT measurements and proposed treatment recommendations using CT
      and MRI classification systems. In the 9-year-old girl, the mean atlanto
      occipital joint width, the interspinous ratio, and space available for cord
      measurements indicated OC dissociation. However, on MRI evaluation, OC
      dissociation was observed in both living siblings and severe ligamentous injury
      was noted in the girl. The proposed CT measuring techniques for the diagnosis of
      OC dissociation were inconsistent in our cases. In the setting of clinically
      suspected OC dissociation with normal CT measurements, we recommend obtaining a
      cervical spine MRI to properly assess the extent of ligamentous injury.

PMID- 30211394
TI  - Use of Three-dimensional Printing in Orthopaedic Surgical Planning.
AB  - Background: Three-dimensional (3D) printing is a technique based on overlapping
      layers of a material (eg, plastic, clay, and metal). The widespread
      implementation of 3D printers has resulted in a notable increase in use. Fields
      such as construction, engineering, and medicine benefit from this technique. Aim:
      The use of 3D printed scale models permits better surgical planning and results.
      Methods: The models were created based on CT images of seven patients (age range,
      5 to 61 years) with different pathologies who were candidates for surgery.
      Results: Surgical time decreased as a result of detailed surgical planning with
      printed models. This technique also was associated with a decrease in bleeding, a
      reduction in the amount of anesthesia required, and greater precision. In some
      patients, a change in surgical strategy was noted, thus allowing for a reduction
      in the number of surgeries and the aggressiveness of surgery. Finally, the
      preoperative practice (virtual and physical osteotomies using cutting tools) that
      was performed in two cases allowed the surgeon to evaluate the different approach
      alternatives and establish the best strategy. Conclusions: The use of 3D-printed
      anatomic models has improved surgical planning, especially for patients in whom
      the conventional techniques are insufficient for establishing a proper strategy.
      The extra information provided by 3D-printed models can lead to a better
      intervention strategy, which is beneficial for patients because it decreases the
      risks, procedure times, and recovery times.

PMID- 30211395
TI  - Surgical Approaches to the Proximal Humerus: A Quantitative Comparison of the
      Deltopectoral Approach and the Anterolateral Acromial Approach.
AB  - Background: Debate exists over the optimal approach for addressing fractures of
      the proximal humerus. The purpose of this study was to objectively quantify the
      surface area of the humerus exposed using the deltopectoral (DP) and
      anterolateral acromial (ALA) approaches and to compare visualized and palpable
      anatomic landmarks. Methods: Ten arms on five fresh-frozen torsos underwent the
      DP and ALA approaches. The arms were positioned to simulate a supine patient and
      held in a fixed position. Visual and/or palpable access to relevant surgical
      landmarks and the myotendinous junctions were recorded. The myotendinous
      junctions were used as a rough approximation of consistent proximal exposure of a
      clinically retracted tuberosity. Landmarks were grouped into quadrants based on
      the location. Calibrated digital photographs of each approach were analyzed to
      calculate the surface area and the length of the exposed bone. Results: The DP
      and ALA approaches exposed 22.9 +/- 6.3 cm2 and 16.3 +/- 6.4 cm2, respectively (P
      = 0.03). The DP and ALA approaches provided equivalent visual and palpable access
      to all landmarks in the superior and inferior quadrants. The ALA allowed improved
      visual (80% versus 70%) and palpable (100% versus 70%) access to the myotendinous
      junction of the infraspinatus in the posterior quadrant. The DP approach allowed
      better access to anterior quadrant structures, including improved ability to
      visualize the myotendinous junction of the subscapularis (100% versus zero), the
      subscapularis insertion (100% versus 80%), and the medial anatomic neck (100%
      versus 20%). Palpable access to the myotendinous junction of the subscapularis
      (100% versus 70%) and medial anatomic neck (100% versus 60%) was also improved
      with the DP. Conclusions: In a cadaver model with fixed arm position, the DP
      provides increased exposure to the proximal humerus and more reliable access to
      anterior surgical landmarks, whereas the ALA allows improved access to the most
      posterior aspect of the shoulder.

PMID- 30211396
TI  - Musculoskeletal Education in Medical Schools: A Survey of Allopathic and
      Osteopathic Medical Students.
AB  - Background: Musculoskeletal (MSK) disorders are one of the most common causes of
      disability and emergency department and physician visits in the United States.
      However, there is very little consistency in how physicians in training are
      prepared to treat MSK disorders. On the basis of published reports, medical
      school graduates have a relative lack of cognitive mastery in MSK medicine, even
      with the recent increase in instruction. This study sought to compare MSK
      education at an allopathic medical school with that at an osteopathic medical
      school. Methods: An anonymous survey of students in medical school graduate years
      2, 3, and 4 at Michigan State University College of Human Medicine (allopathic)
      and College of Osteopathic Medicine (osteopathic) was conducted. Questions were
      structured into three main categories: demographic information, content of the
      current MSK curriculum, and opinions regarding importance, instruction, and
      assessment of MSK education. Results: As of 2010, 83% of medical schools require
      MSK courses because of the United States Bone and Joint Initiative to incorporate
      such coursework into core curriculum. Yet only 54% of surveyed students thought
      that their MSK education was adequate. A greater portion of osteopathic students
      (57.1%) compared with allopathic students (26.8%) thought that their MSK
      curriculum is adequate, and as a consequence, 36.6% of allopathic students
      thought that they were inadequately prepared for the MSK content of US medical
      licensing examinations compared with 8.1% of osteopathic students. Further
      curriculum development and improvement is needed to advance physicians' abilities
      to address and treat MSK disorders. Medical students surveyed feel that this goal
      can be accomplished by emphasizing MSK education in third and fourth years of
      medical school. Conclusion: These findings highlight differences in MSK education
      between an allopathic and osteopathic medical school. Further standardization of
      the curriculum in medical schools may help improve the quality of teaching
      student comfort levels of new physicians. Level of Evidence: Level III.

PMID- 30211397
TI  - Risk Factors for Facial Pain: Data from the Osteoarthritis Initiative Study.
AB  - Aims: Temporomandibular disorder (TMD) is believed to be co-morbid with
      rheumatologic conditions such as Osteoarthritis (OA). We determine 30-day
      prevalence and cumulative incidence, and risk factors for facial pain in a cohort
      of subjects who either had or were at risk of developing symptomatic radiographic
      knee osteoarthritis (SRKOA). Methods: Poisson regression models examined whether
      age, sex, race, Center for Epidemiologic Studies-Depression Scale (CES-D) score,
      number of painful joints, and presence of SRKOA were risk factors for facial pain
      in 4,423 subjects at baseline and in 3,472 subjects at 24 and/or 48 months follow
      up. Results: At baseline, 30-day period prevalence of facial pain was 9.25%; and
      30-day cumulative incidence at 24-months and at 48-months was 5.9% and 4.9%,
      respectively. Factors associated with prevalence and incidence of facial pain
      were: younger age, female sex, (CES-D) score, and a larger number of painful
      joints. For each increase in age of one year, the incidence of facial pain
      decreased by 1%. Women had a 96% higher incidence than men, and each unit
      increase of (CES-D) score was associated with a 2% increase in the incidence of
      facial pain. For every additional painful joint, there was a 21% increase in the
      incidence of facial pain. Subjects with SRKOA had a 33% increase in the incidence
      of facial pain compared to those with risk factors for SRKOA. Conclusion: OA and
      TMD share several risk factors. The risk factors identified in cross-sectional
      analysis of prevalence are similar to those identified in longitudinal analysis
      on incidence.

PMID- 30211398
TI  - Mesenchymal stem cell derived extracellular vesicles: a promising new therapeutic
      approach for hepatic injury.

PMID- 30211399
TI  - Enantioselectively functionalised phenytoin derivatives by auxiliary-directed N
      to C aryl migration in lithiated alpha-amino nitriles.
AB  - Lithiation of N'-arylureas derived from amino nitriles incorporating a (1R,2R)-2
      aminocyclohexanol chiral auxiliary leads to diastereoselective migration of the
      aryl ring to the position alpha to the nitrile. The resulting N'-lithiated ureas
      undergo spontaneous cyclisation to iminohydantoins, which may be hydrolysed to
      give chiral 5,5-diarylhydantoins related to phenytoin, in enantioenriched form.

PMID- 30211401
TI  - Use of inorganic fluorinated materials in lithium batteries and in energy
      conversion systems.
AB  - After a review on the wide variety of inorganic fluorinated components in modern
      technologies, in particular for energy conversion/storage systems, the use of
      fluorinated carbons as electrodes for primary lithium batteries will be
      highlighted; in particular conventional graphite fluorides will be compared to
      recently investigated fluorinated carbon nanoparticles (F-CNPs) prepared from
      electrochemical reduction of molten carbonates.

PMID- 30211403
TI  - Direct imaging of a single Ni atom cutting graphene to form a graphene nanomesh.
AB  - A large area graphene nanomesh (GNM) etched by Ni is synthesized by a facile one
      step liquid arc discharge in a Ni-containing solution. Atomic-resolution scanning
      transmission electron microscopy (STEM) combined with electron energy loss
      spectroscopy (EELS) is applied to identify the atomic structures of the product.
      The results show that the GNM with a pore size of about 10-50 nm comprises single
      or few layer graphene, and there are some small pores of size 1 nm and defects
      of five membered rings or seven membered rings in the positions of the skeletons.
      Also Ni atoms or nanoparticles are uniformly distributed in graphene or at the
      edges of the GNM. A dynamic study using a microscope shows that the Ni atom at
      the edge of graphene is active and can move along the edge, which facilitates the
      fracture of C-C bonds and the diffusion of carbon atoms greatly. DFT calculation
      results show that the diffusion of carbon atoms along the edge in the GNM
      containing Ni is easier than that in pristine graphene. The Ni atoms or particles
      act as an "atomic knife" to cut the graphene sheet to feed the formation of the
      GNM. These results represent a significant advancement in the growth mechanism
      study of GNMs and thus the precise structure control of graphene.

PMID- 30211404
TI  - Exploitation of Eu3+ red luminescence through order-disorder structural
      transitions in lanthanide stannate pyrochlores for warm white LED applications.
AB  - Eu3+ ions epitomize excellent structural probes for the detection of disorder
      induced by structural variations in stannate pyrochlores due to their relatively
      simple energy level structure. In this context, we have synthesized a series of
      Eu3+ doped Ln2.85YSnNbO10.5:0.15Eu3+ (Ln = La, Gd, Y, and Lu) red phosphors via a
      high temperature solid state reaction method to explore the influence of phase
      evolution on the luminescence properties. The substitution of Ln3+ ions in the A
      sites of the pyrochlore induces a structural transition from an ordered
      pyrochlore to a disordered fluorite structure with decreasing ionic radius. The
      diminishing trend of the characteristic superstructure peaks in the XRD pattern
      and the broadening of Raman modes with lanthanide substitution clearly
      substantiate the disorder induced in the cationic sublattice. These phosphors
      exhibit strong absorption in the near UV region and emit red luminescence under
      392 nm excitation, which also correlates to their crystal structures. Their
      luminescence properties were enhanced with the increased ordering of cations from
      Lu to La. The more ordered structure of the La system favors a more uniform
      distribution of Eu3+ ions, preventing cluster formation, and thus improving the
      luminescence properties. The splitting of the 5D0-7F1 transition of the Eu3+ ions
      further provides a clue for the structural transition in support of the XRD and
      Raman analysis. The long range ordering, ligand polarizability, and covalent
      nature of the Eu3+ bonding influence the emission probability and improve the
      quantum efficiency of the La host. Eu3+ emissions resulting from 5D0-7FJ
      transitions are significantly improved with increases in the concentration of
      Eu3+ ions in the La host. The distortion of the A site symmetry and the red shift
      of the charge transfer band with Eu3+ doping in the La3YSnNbO10.5 system leads to
      an enhanced electric dipole transition. The extent of the distortion in the EuO8
      polyhedra is reflected in the quantum efficiency values and J-O intensity
      parameters, Omega2 and Omega4, which are a measure of the degree of
      polarizability of the Eu-O bonds in the lattice. Our results suggest that we can
      manipulate the Eu3+ red luminescence in lanthanide stannate pyrochlores through
      order-disorder structural transitions.

PMID- 30211405
TI  - Ethane diffusion in mixed linker zeolitic imidazolate framework-7-8 by pulsed
      field gradient NMR in combination with single crystal IR microscopy.
AB  - Pulsed field gradient (PFG) NMR was used in combination with single crystal IR
      microscopy (IRM) to study diffusion of ethane inside crystals of a mixed linker
      zeolitic imidazolate framework (ZIF) of the type ZIF-7-8 under comparable
      experimental conditions. These crystals contain 2-methylimidazolate (ZIF-8
      linker) and benzimidazolate (ZIF-7 linker). It was observed that the PFG NMR
      attenuation curves measured for ethane in ZIF-7-8 exhibit deviations from the
      monoexponential behaviour, thereby indicating that the ethane self-diffusivity in
      different crystals of a crystal bed can be different. Measurements of the ethane
      uptake curves performed by IRM under the same conditions in different ZIF-7-8
      crystals of the bed yield different transport diffusivities thus confirming that
      the rate of ethane diffusion is different in different ZIF-7-8 crystals. The IRM
      observation that the fractions of ZIF-8 and ZIF-7 linkers are different in
      different ZIF-7-8 crystals allowed attributing the observed heterogeneity in
      diffusivities to the heterogeneity in the linker fraction. The quantitative
      comparison of the average ethane self-diffusivities measured by PFG NMR in ZIF-7
      8 with the corresponding data on corrected diffusivities from IRM measurements
      revealed a good agreement between the results obtained by the two techniques. In
      agreement with the expectation of smaller aperture sizes in ZIF-7-8 than in ZIF
      8, the average ethane self-diffusivities in ZIF-7-8 were found to be
      significantly lower than the corresponding self-diffusivities in ZIF-8.

PMID- 30211406
TI  - Experimental study and computational modelling of cruzain cysteine protease
      inhibition by dipeptidyl nitriles.
AB  - Chagas disease affects millions of people in Latin America. This disease is
      caused by the protozoan parasite Trypanossoma cruzi. The cysteine protease
      cruzain is a key enzyme for the survival and propagation of this parasite
      lifecycle. Nitrile-based inhibitors are efficient inhibitors of cruzain that bind
      by forming a covalent bond with this enzyme. Here, three nitrile-based inhibitors
      dubbed Neq0409, Neq0410 and Neq0570 were synthesized, and the thermodynamic
      profile of the bimolecular interaction with cruzain was determined using
      isothermal titration calorimetry (ITC). The result suggests the inhibition
      process is enthalpy driven, with a detrimental contribution of entropy. In
      addition, we have used hybrid Quantum Mechanical/Molecular Mechanical (QM/MM) and
      Molecular Dynamics (MD) simulations to investigate the reaction mechanism of
      reversible covalent modification of cruzain by Neq0409, Neq0410 and Neq0570. The
      computed free energy profile shows that the nucleophilic attack of Cys25 on the
      carbon C1 of inhibitiors and the proton transfer from His162 to N1 of the
      dipeptidyl nitrile inhibitor take place in a single step. The calculated free
      energy of the inhibiton reaction is in agreement with covalent experimental
      binding. Altogether, the results reported here suggests that nitrile-based
      inhibitors are good candidates for the development of reversible covalent
      inhibitors of cruzain and other cysteine proteases.

PMID- 30211407
TI  - Bexarotene cannot reduce amyloid beta plaques through inhibition of production of
      amyloid beta peptides: in silico and in vitro study.
AB  - Recently, it has been reported that anti-cancer drug bexarotene can remarkably
      destroy amyloid beta (Abeta) plaques in mouse models suggesting therapeutic
      potential for Alzheimer's disease. However, the effect of bexarotene on clearance
      of plaques has not been seen in some mouse models. One of the possible mechanisms
      explaining this phenomenon is that bexarotene levels up expression of
      apolipoprotein 4 (ApoE4) leading to intracellular clearance of Abeta peptide.
      Therefore, an interesting question emerges of whether bexarotene can destroy
      Abeta plaques by direct interaction with them or by preventing production of
      Abeta peptides. In our previous work we have shown that bexarotene cannot clear
      amyloid aggregates due to their weak interaction using in silico and in vitro
      experiments. Here we explore the possibility of inhibiting Abeta production
      through bexarotene binding to beta-secretase which can cleave Abeta peptides from
      amyloid precursor protein. Using the molecular mechanics-Poisson-Boltzmann
      surface area method and all-atom simulations we have shown that bexarotene has a
      very low binding affinity to beta-secretase. This result has been also confirmed
      by our in vitro experiment implying that bexarotene cannot clear amyloid plaques
      through inhibition of Abeta production. We have also shown that bexarotene
      tightly binds to both peroxisome proliferator-activated receptor gamma (PPAR
      gamma) and retinoid X receptors (RXRs). Thus, our result does not contradict the
      hypothesis that the reduction of Abeta plaques occurs due to bexarotene-induced
      overexpression of ApoE4.

PMID- 30211408
TI  - Strong and insusceptible photo-emissions from an intramolecular weak hydrogen
      bond strengthened twisted fluorophore.
AB  - Intramolecular weak hydrogen bonds of CHO and CH/Pi were introduced into a
      twisted fluorophore backbone of 1,4-bis(2,2-diphenylvinyl)benzene, which enables
      the fluorophore to emit violently and stably in both solubilized and aggregated
      states, and be inert to solvent environments and preserve over 10% quantum yield
      at temperature as high as 90  degrees C in solution.

PMID- 30211411
TI  - Strain-driven carrier-type switching of surface two-dimensional electron and hole
      gases in a KTaO3 thin film.
AB  - Since the discovery of a two-dimensional (2D) electron gas at the LaAlO3/SrTiO3
      interface, 2D carrier gases at such oxide interfaces and surfaces have attracted
      great attention because they can host many important phenomena and may produce
      novel functional devices. Here, we show through first-principles investigations
      that the surface 2D electron and hole gases in a KTaO3 (KTO) thin film can be
      tuned by applying biaxial stress. When increasing compressive in-plane strain,
      the 2D carrier concentrations decrease down to zero and then a new pair of
      surface 2D electron and hole gases appears in which the carrier types are
      switched to the opposite ones. Our analysis indicates that this carrier-type
      switching occurs because the increasing compressive strain reverses the slope of
      monolayer-resolved electrostatic potential along the [001] direction. We also
      present strain-dependent carrier concentrations and effective masses, and explore
      their thickness dependence. It is further shown that the 2D carrier gases and
      their strain-driven carrier-type switching across the KTO layer still remain true
      in the presence of overlayers and epitaxial substrates. These phenomena should be
      useful to design novel functional devices.

PMID- 30211409
TI  - Chemical kinetics in an atmospheric pressure helium plasma containing humidity.
AB  - Atmospheric pressure plasmas are sources of biologically active oxygen and
      nitrogen species, which makes them potentially suitable for the use as biomedical
      devices. Here, experiments and simulations are combined to investigate the
      formation of the key reactive oxygen species, atomic oxygen (O) and hydroxyl
      radicals (OH), in a radio-frequency driven atmospheric pressure plasma jet
      operated in humidified helium. Vacuum ultra-violet high-resolution Fourier
      transform absorption spectroscopy and ultra-violet broad-band absorption
      spectroscopy are used to measure absolute densities of O and OH. These densities
      increase with increasing H2O content in the feed gas, and approach saturation
      values at higher admixtures on the order of 3 * 1014 cm-3 for OH and 3 * 1013 cm
      3 for O. Experimental results are used to benchmark densities obtained from zero
      dimensional plasma chemical kinetics simulations, which reveal the dominant
      formation pathways. At low humidity content, O is formed from OH+ by proton
      transfer to H2O, which also initiates the formation of large cluster ions. At
      higher humidity content, O is created by reactions between OH radicals, and lost
      by recombination with OH. OH is produced mainly from H2O+ by proton transfer to
      H2O and by electron impact dissociation of H2O. It is lost by reactions with
      other OH molecules to form either H2O + O or H2O2. Formation pathways change as a
      function of humidity content and position in the plasma channel. The
      understanding of the chemical kinetics of O and OH gained in this work will help
      in the development of plasma tailoring strategies to optimise their densities in
      applications.

PMID- 30211413
TI  - Highly enhanced liquid flows via thermoosmotic effects in soft and charged
      nanochannels.
AB  - Enhancing nanoscale liquid flows remains an existing challenge in nanofluidics.
      Here we propose the generation of highly augmented thermoosmotic (TOS) liquid
      flows in soft nanochannels (or nanochannels functionalized by grafting with end
      charged polyelectrolyte or PE brushes) by employing an axial temperature
      gradient. The TOS transport is a combination of the induced-electric-field
      electroosmotic (EOS) transport and a thermo-chemioosmotic (TCOS) transport with
      the latter resulting from an induced pressure gradient on account of the changes
      associated with the imposition of the axial temperature gradient. The end-charged
      brushes develop an electric double layer (EDL) localized at the charged, non
      grafted brush end. Depending on the system parameters, this EDL localization
      massively augments the influence of the EOS body force and the induced pressure
      gradient resulting in a TOS transport in soft nanochannels that can be more than
      one order of magnitude larger than that in brush-free nanochannels. Given the
      existing notion that the presence of the brushes invariably reduces the flow
      strength, this result of massive flow augmentation is extremely significant and
      non-trivial serving as a paradigm shift in the study of liquid transport in brush
      grafted nanochannels.

PMID- 30211412
TI  - The nature of frontier orbitals under systematic ligand exchange in (pseudo
      )octahedral Fe(ii) complexes.
AB  - Understanding and controlling properties of transition metal complexes is a
      crucial step towards tailoring materials for sustainable energy applications. In
      a systematic approach, we use resonant inelastic X-ray scattering to study the
      influence of ligand substitution on the valence electronic structure around an
      aqueous iron(ii) center. Exchanging cyanide with 2-2'-bipyridine ligands reshapes
      frontier orbitals in a way that reduces metal 3d charge delocalization onto the
      ligands. This net decrease of metal-ligand covalency results in lower metal
      centered excited state energies in agreement with previously reported excited
      state dynamics. Furthermore, traces of solvent-effects were found indicating a
      varying interaction strength of the solvent with ligands of different character.
      Our results demonstrate how ligand exchange can be exploited to shape frontier
      orbitals of transition metal complexes in solution-phase chemistry; insights upon
      which future efforts can built when tailoring the functionality of photoactive
      systems for light-harvesting applications.

PMID- 30211414
TI  - Spatial and orientational dependence of electron transfer parameters in
      aggregates of iridium-containing host materials for OLEDs: coupling constrained
      density functional theory with molecular dynamics.
AB  - The efficient transport of charge within the bulk of active molecular materials
      is one of the main factors affecting the efficiency and performance of organic
      electronic devices. In amorphous molecular aggregates, the observed effective
      mobility of charge carriers is usually considered as resulting from the
      convolution of the manifold of intermolecular configurations. In this picture,
      individual molecules are considered as spherically-symmetric scattering points
      for charge hopping. Yet, the details of the molecular structure and the topology
      of the electronic states involved in the charge transport mechanism affect
      dramatically the intermolecular electronic coupling even in amorphous materials.
      In this work, we link the morphology of aggregates, in terms of intermolecular
      configurations, as obtained from atomistic molecular dynamics, to the
      distribution of diabatic electronic couplings and charge transfer energies,
      computed by constrained density functional theory simulations. In particular, we
      focus on aggregates of an organometallic system with multidentate ligands, the
      iridium complex fac-tris(1,3-diphenyl-benzimidazolin-2-ylidene-C,C2')iridium(iii)
      (DPBIC), commonly used in OLEDs as host transporter and emitter. Despite the
      quasi-spherical symmetry of the molecule, our simulations suggest a strong
      correlation between intermolecular orientation and electronic coupling,
      indicating a strong impact of the mutual orientation of molecules on charge
      transport in bulk molecular materials.

PMID- 30211417
TI  - Cd induces G2/M cell cycle arrest by up-regulating miR-133b via directly
      targeting PPP2R2D in L02 hepatocytes.
AB  - Previous research has shown that cadmium (Cd), which accumulates primarily in the
      liver and kidneys, could cause cell cycle arrest in various cell types. In the
      present study, the effect of Cd on the cell cycle progression of hepatocytes and
      the underlying mechanisms were investigated. Our results showed that Cd inhibited
      the growth and proliferation of L02 hepatocytes. Further study revealed that Cd
      significantly induced G2-phase cell cycle arrest accompanied by an overproduction
      of reactive oxygen species (ROS). Cd-induced G2-phase arrest could be prevented
      by inhibiting ROS with the use of antioxidant Trolox. Additionally, treatment
      with Cd induced an increase in the expression of miR-133b, which could be
      reversed with Trolox pretreatment. Moreover, miR-133b was shown to regulate
      PPP2R2D expression by binding to the 3'-untranslated region (UTR) of PPP2R2D
      mRNA. We also found that treatment with Cd decreased the expression of PPP2R2D,
      and inhibition of PPP2R2D expression by siRNA partially aggravated Cd-induced
      cell cycle arrest. By artificially increasing the expression of the protein
      phosphatase 2A-B55delta subunit (PP2A-B55delta, encoded by the PPP2R2D gene), we
      confirmed that PPP2R2D can be regulated by miR-133b in Cd-treated cells, and the
      G2-phase arrest effect could be suppressed by PP2A-B55delta. Collectively, these
      findings indicated that Cd increased ROS and induced the expression of miR-133b,
      which consequently inhibited the expression of PPP2R2D and led to G2-phase arrest
      in L02 hepatocytes. This study provides novel insights into the molecular
      mechanisms of Cd-induced cell cycle arrest.

PMID- 30211419
TI  - The influence of absorbing boundary conditions on the transition path time
      statistics.
AB  - We derive an analytical expression for the transition path time (TPT)
      distribution for a one-dimensional particle crossing a parabolic barrier. The
      solution is expressed in terms of the eigenfunctions and eigenvalues of the
      associated Fokker-Planck equation. The particle exhibits anomalous dynamics
      generated by a power-law memory kernel, which includes memoryless Markovian
      dynamics as a limiting case. Our result takes into account absorbing boundary
      conditions, extending existing results obtained for free boundaries. We show that
      TPT distributions obtained from numerical simulations are in excellent agreement
      with analytical results, while the typically employed free boundary conditions
      lead to a systematic overestimation of the barrier height. These findings may be
      useful in the analysis of experimental results on the transition path time. A web
      tool to perform this analysis is freely available.

PMID- 30211418
TI  - Single-platform 'multi-omic' profiling: unified mass spectrometry and
      computational workflows for integrative proteomics-metabolomics analysis.
AB  - The objective of omics studies is to globally measure the different classes of
      cellular biomolecules present in a biological specimen (e.g. proteins,
      metabolites) as accurately as possible in order to investigate the corresponding
      'states' of biological systems. High throughput omics technologies are emerging
      as an increasingly powerful toolkit in the rapidly advancing field of systems
      biology, enabling the systematic study of dynamic molecular processes that drive
      core cell functions like growth, sensing, and environmental adaptation. Advances
      in high resolution mass spectrometry, in particular, now allow for the near
      comprehensive study of cellular proteins and metabolites that underlie
      physiological homeostasis and disease pathogenesis. Yet while the expression
      levels, modification states, and functional associations of diverse molecular
      species are now measurable, existing proteomic and metabolomic data generation
      and analysis workflows are often specialized and incompatible. Hence, while there
      are now many reports of ad hoc combinations of unimolecular proteomic and
      metabolomic workflows, only a limited number of multi-omic profiling approaches
      have been reported for obtaining different molecular measurements (proteins,
      metabolites, nucleic acids) in parallel from a single biological sample.
      Moreover, elucidating how the myriad of measured cellular components are linked
      together functionally within the metabolic processes, signal transduction
      pathways, and macromolecular interaction networks central to living systems
      remains a massive, complicated, and uncertain endeavor. Presented here is a
      review of convergent mass spectrometry-based multi-omic methodologies, with a
      focus on notable recent advances and remaining challenges in terms of efficient
      sample preparation, biochemical separations, data acquisition, and integrative
      computational strategies. We outline a unifying network-based integrative
      framework to better derive biological knowledge from integrated profiling studies
      with the goal of realizing the full potential of multi-omic data sets.

PMID- 30211420
TI  - Predicting the conductance of strongly correlated molecules: the Kondo effect in
      perchlorotriphenylmethyl/Au junctions.
AB  - Stable organic radicals integrated into molecular junctions represent a practical
      realization of the single-orbital Anderson impurity model. Motivated by recent
      experiments for perchlorotriphenylmethyl (PTM) molecules contacted to gold
      electrodes, we develop a method that combines density functional theory (DFT),
      quantum transport theory, numerical renormalization group (NRG) calculations and
      renormalized super-perturbation theory (rSPT) to compute both equilibrium and non
      equilibrium properties of strongly correlated nanoscale systems at low
      temperatures effectively from first principles. We determine the possible atomic
      structures of the interfaces between the molecule and the electrodes, which allow
      us to estimate the Kondo temperature and the characteristic transport properties,
      which compare well with experiments. By using the non-equilibrium rSPT results we
      assess the range of validity of equilibrium DFT + NRG-based transmission
      calculations for the evaluation of the finite voltage conductance. The results
      demonstrate that our method can provide qualitative insights into the properties
      of molecular junctions when the molecule-metal contacts are amorphous or
      generally ill-defined, and that it can further give a fully quantitative
      description when the experimental contact structures are well characterized.

PMID- 30211421
TI  - All-in-one NIR-activated nanoplatforms for enhanced bacterial biofilm
      eradication.
AB  - The chronic infection of humans by antibiotic-resistant bacteria and their
      related biofilm have, so far, not been properly addressed. In the present work,
      we developed a novel antibacterial nanoplatform showing the most efficient
      antibiotic-resistant bacteria inhibition and biofilm eradication. This particular
      formulation contains tobramycin-conjugated graphene oxide, for efficiently
      capturing bacteria through electrostatic interactions and eliminating bacteria as
      a "nano-knife", and copper sulphide nanoparticles for enhancing the photothermal
      and photodynamic properties. This novel formulation can selectively eliminate
      bacteria over NIH 3T3 cells, and the biofilm eradication capacity was up to 70%.
      Importantly, the nanoplatforms can inhibit bacterial growth and promote the
      repair of antibiotic-resistant bacteria-infected wounds on rats without non
      specific damage to normal tissue. This work provides an effective, simple, and
      rapid method for the design and fabrication of near-infrared light-induced
      nanoplatforms that offer possibilities to treat biofilm-related infections.

PMID- 30211422
TI  - Polarization-based super-resolution imaging of surface-enhanced Raman scattering
      nanoparticles with orientational information.
AB  - Raman scattering provides key information of the biological environment through
      light-molecule interaction; yet, it is generally very weak to detect. Surface
      enhanced Raman scattering (SERS) can boost the Raman signal by several orders-of
      magnitude, and thus is highly attractive for biochemical sensing. However,
      conventional super-resolution imaging of SERS is challenging as the Raman signal
      is generated from the virtual state which cannot be easily modulated as
      fluorescence. Here, we demonstrate super-resolution microscopy with a surface
      enhanced Raman scattering (SERS) signal, with a resolution of approximately 50
      nm. By modulating the polarization angle of the excitation laser, the SERS
      nanorods display a dramatic anisotropy effect, allowing nanoscale orientation
      determination of multiple dipoles with dense concentration. Furthermore, a well
      established defocused analysis was performed to reconfirm the orientation
      accuracy of super-resolved SERS nanorods. Sub-diffraction resolution was achieved
      in the imaging of SERS nanorod labeled vesicles in fixed macrophages. Finally, we
      demonstrate dynamic SERS nanorod tracking in living macrophages, which provides
      not only the particle trajectory with high spatial resolution but also the
      rotational changes at the nanometer scale. This pioneering study paves a new way
      for subcellular super-resolution imaging with the SERS effect, shedding light on
      wider biological applications.

PMID- 30211423
TI  - Wireless piezoelectric devices based on electrospun PVDF/BaTiO3 NW nanocomposite
      fibers for human motion monitoring.
AB  - Real-time personalized motion monitoring and analysis are important for human
      health. Thus, to satisfy the needs in this area and the ever-increasing demand
      for wearable electronics, we design and develop a wireless piezoelectric device
      consisting of a piezoelectric pressure sensor based on electrospun PVDF/BaTiO3
      nanowire (NW) nanocomposite fibers and a wireless circuit system integrated with
      a data conversion control module, a signal acquisition and amplification module,
      and a Bluetooth module. Finally, real-time piezoelectric signals of human motion
      can be displayed by an App on an Android mobile phone for wireless monitoring and
      analysis. This wireless piezoelectric device is proven to be sensitive to human
      motion such as squatting up and down, walking, and running. The results indicate
      that our wireless piezoelectric device has potential applications in wearable
      medical electronics, particularly in the fields of rehabilitation and sports
      medicine.

PMID- 30211424
TI  - Bio-based glyco-bolaamphiphile forms a temperature-responsive hydrogel with
      tunable elastic properties.
AB  - A bio-based glycolipid bolaamphiphile (glyco-bolaamphiphile) has recently been
      produced (Van Renterghem et al., Biotechnol. Bioeng., 2018, 115, 1195-1206) on a
      gram scale by using the genetically-engineered S. bombicola strain Deltaat
      Deltasble Deltafao1. The glyco-bolaamphiphile bears two symmetrical sophorose
      headgroups at the extremities of a C16:0 (omega-1 hydroxylated palmitic alcohol)
      spacer. Its atypical structure has been obtained by redesigning the S. bombicola
      strain Deltaat Deltasble, producing non-symmetrical glyco-bolaamphiphile, with an
      additional knock out (Deltafao1) and feeding this new strain with fatty alcohols.
      The molecular structure of the glyco-bolaamphiphile is obtained by feeding the
      new strain a saturated C16 substrate (palmitic alcohol), which enables the
      biosynthesis of bolaform glycolipids. In this work, we show that the bio-based
      glyco-bolaamphiphile readily forms a hydrogel in water at room temperature, and
      that the hydrogel formation depends on the formation of self-assembled fibers.
      Above 28  degrees C, the molecules undergo a gel-to-sol transition, which is due
      to a fiber-to-micelle phase change. We provide a quantitative description of the
      Self-Assembled Fibrillar Network (SAFiN) hydrogel formed by the glyco
      bolaampiphile. We identify the sol-gel transition temperature, the gelling time,
      and the minimal gel concentration; additionally, we explore the fibrillation
      mechanism as a function of time and temperature and determine the activation
      energy of the micelle-to-fiber phase transition. These parameters allow control
      of the elastic properties of the glyco-bolaamphiphile hydrogel: at 3 wt% and 25 
      degrees C, the elastic modulus G' is above the kPa range, while at 5  degrees C,
      G' can be tuned between 100 Pa and 20 kPa, by controlling the undercooling
      protocol.

PMID- 30211427
TI  - Three dimensionally-ordered 2D MoS2 vertical layers integrated on flexible
      substrates with stretch-tunable functionality and improved sensing capability.
AB  - The intrinsically anisotropic crystallinity of two-dimensional (2D) transition
      metal dichalcogenide (2D TMD) layers enables a variety of intriguing material
      properties which strongly depend on the physical orientation of constituent 2D
      layers. For instance, 2D TMDs with vertically-aligned layers exhibit numerous
      dangling bonds on their 2D layer edge sites predominantly exposed on the surface,
      projecting significantly improved physical and/or chemical adsorption capability
      compared to their horizontally-oriented 2D layer counterparts. Such property
      advantages can be further promoted as far as the material can be integrated onto
      unconventional substrates of tailored geometry/functionality, offering vast
      opportunities for a wide range of applications which demand enhanced surface
      area/reactivity and mechanical flexibility. Herein, we report a new form of 2D
      TMDs, i.e., three-dimensionally ordered 2D molybdenum disulfide (2D MoS2) with
      vertically-aligned layers integrated on elastomeric substrates and explore their
      tunable multi-functionalities and technological promise. We grew large-scale (>2
      cm2) vertically-aligned 2D MoS2 layers using a three-dimensionally patterned
      silicon dioxide (SiO2) template and directly transferred/integrated them onto
      flexible polydimethylsiloxane (PDMS) substrates by taking advantage of the
      distinguishable water-wettability of 2D MoS2vs. SiO2. The excellent structural
      integrity of the integrated vertical 2D MoS2 layers was confirmed by extensive
      spectroscopy/microscopy characterization. In addition, the stretch-driven unique
      tunability of their optical and surface properties was also examined. Moreover,
      we applied this material for flexible humidity sensing and identified
      significantly improved (>10 times) sensitivity over conventionally-designed
      horizontal 2D MoS2 layers, further confirming their high potential for
      unconventional flexible technologies.

PMID- 30211428
TI  - One-dimensional nanostructures of II-VI ternary alloys: synthesis, optical
      properties, and applications.
AB  - One-dimensional (1D) nanostructures of II-VI ternary alloys are of prime interest
      due to their compatible features of both 1D nanostructures and semiconducting
      alloys. These features can facilitate materials with tunable bandgaps, which are
      crucial to the performance of photoelectrical devices. Herein, we present a
      comprehensive review summarizing the recent research progress pertinent to the
      diverse synthesis, optical fundamentals and applications of 1D nanostructures of
      II-VI ternary alloys. Considering multifunctional applications, the different
      growth mechanisms of the rational design and synthesis techniques are
      highlighted. Investigations of the fundamentals of the optical and
      photoelectrical properties of ternary alloyed II-VI semiconductors via the
      corresponding characterization techniques are also particularly discussed.
      Furthermore, we present the versatile potential practical applications of these
      materials. Finally, we extend the discussion to the most recent research advances
      on quaternary alloys, which provides a possible prospective forecast for the
      sustained development of alloyed 1D nanostructures.

PMID- 30211434
TI  - Pancreatic theory of relativity....
AB  - Pancreatic duct and parenchyma has different benchmarks in nomenclature. Author
      discuss the proposition to unify the description system of procedures and
      surgeries within pancreas according to the direction of pancreatic juice natural
      flow direction.

PMID- 30211430
TI  - Self-assembly of clay nanotubes on hair surface for medical and cosmetic
      formulations.
AB  - While most hair care formulations are developed on the basis of surfactants or
      polymers, we introduce self-assembly coating of micro and nanoparticles as the
      underlying principle for hair modification, protection and enhancement.
      Halloysite clay nanotubes formed by rolled sheets of aluminosilicate kaolin
      assemble on the surface of hair forming a robust multilayer coverage. Prior to
      the application, clay nanotubes were loaded with selected dyes or drug allowing
      for hair coloring or medical treatment. This facile process is based on a 3
      minute application of 1 wt% aqueous dispersion of color/drug loaded halloysite
      resulting in a ca. 3 MUm thick uniform hair surface coating. This technique,
      which employs a very safe, biocompatible and inexpensive material, is ubiquitous
      with respect to the species of source of hair and additives in solvent, making it
      viable as an excipient for conventional medical and veterinarian formulations.

PMID- 30211433
TI  - Lipopolysaccharide induces the early enhancement of mice colonic mucosal
      paracellular permeability mainly mediated by mast cells.
AB  - The alteration of intestinal mucosal barrier is considered to be the central
      pathophysiological process in response to gastrointestinal infections, and
      mucosal microstructural damage is a major factor for enhancing epithelial
      permeability in persistent bacterial infections. However, the mechanism involved
      in hyperpermeability in the early stage of acute bacterial infections is not
      fully understood. In the present study, fluorescein isothiocyanate-dextran across
      and transepithelial resistance measured in Ussing chambers were used to assess
      the intestinal paracellular permeability. Mast cell activation was evaluated by
      western blotting for the presence of tryptase released from mast cells. Serum
      levels of interleukin-6 were evaluated using enzyme-linked immunosorbent assay.
      Our results indicated that mast cells played a pivotal role in colonic mucosal
      hyperpermeability in wild type mice treated with lipopolysaccharide (LPS) for 2
      h. And the effect of LPS was mainly dependent on mast cell degranulation, while
      no change in permeability was observed in the mast cell-deficient mice (Wads-/-)
      after LPS administration. No obvious changes of the mucosal structure including
      histomorphological architecture and expression of intercellular junction proteins
      were obtained in either wild type or Wads-/-18 mice after LPS stimulation by
      hematoxylin and eosin staining, immunofluorescence staining and western blot
      analysis. Furthermore, the self-renewal of intestinal epithelia, detected by
      using proliferation marker 5'-bromo-2'-deoxyuridine, was not involved in
      increased permeability. Collectively, activation of mast cells induced by LPS
      mediated intestinal hyperpermeability in the initial stage, and played a crucial
      role in barrier dysfunction rather than mucosal microstructural damage in acute
      enterogenous bacterial infection.

PMID- 30211435
TI  - Predictors of aortic stenosis severity reclassification with imaging data fusion
      method in patients qualified for TAVI.
AB  - : B: ACKGROUND: Imaging data fusion method (IDFM) with multislice computed
      tomography (MSCT) and two-dimensional transthoracic echocardiography (2D-TTE) in
      aortic stenosis (AS) may result in reclassification from severe to non-severe AS.
      AIM: The aim of the study was to establish potential predictors of AS
      reclassification with IDFM method. METHODS: 54 high-risk patients (mean age 79+/
      7.9 years; 40.7% male) with severe AS by 2D-TTE (indexed aortic valve area [AVAi]
      < 0.6 cm2/m2), qualified for transcatheter aortic valve implantation (TAVI), were
      included in the analysis. AVAi was then recalculated with IDFM by replacing 2D
      TTE left ventricular outflow tract (LVOT) measurements with MSCT LVOT parameters.
      RESULTS: IDFM reclassified 20.4% patients as potentially non-severe AS. In a
      multivariable model including clinical variables, reclassification to non-severe
      AS by IDFM was independently associated with younger age and diabetes mellitus
      (DM), (Odds Ratio (OR): 0.864; 95% CI: 0.76-0.99; P < 0.035 and OR: 19.259; 95%
      CI: 2.28-162.41; P < 0.007, respectively). In a multivariable model including
      echocardiographic variables, reclassification was associated with: higher LVOT
      velocity time integral (VTILVOT) and lower aortic mean gradient (AMG) (OR: 1.402;
      95% CI: 1.07-1.84; P < 0.014 and OR: 0.858; 95%: CI: 0.760-0.968; P < 0.013,
      respectively). In addition 24.1% of patients were reallocated from low-flow (< 35
      mL/m2) to normal-flow AS. CONCLUSIONS: IDFM reclassified a substantial proportion
      of patients with severe AS into potentially moderate AS group and from low-flow
      to normal-flow AS group. Such regrouping calls for increased diagnostic prudence
      in AS patients, especially those with specific clinical and echocardiographic
      predictors of reclassification, such as DM or low AMG.

PMID- 30211436
TI  - Adherence in patients with atrial fibrillation treated with dabigatran.

PMID- 30211438
TI  - Role of the learning curve in very high-risk patients treated with MitraClip
      device for functional mitral regurgitation: a single-centre experience.

PMID- 30211437
TI  - NOninvasive Monitoring for Early Detection of Atrial Fibrillation: rationale and
      design of the NOMED-AF study.

PMID- 30211439
TI  - Metaboreceptor polymorphisms: do genes determine your blood pressure response to
      exercise?

PMID- 30211440
TI  - Parental factors in early childhood are associated with approximal caries
      experience in young adults-A longitudinal study.
AB  - OBJECTIVES: To test the hypothesis that parental factors in early childhood
      influence approximal caries experience in young adults. METHODS: A cohort of 494
      individuals was followed longitudinally from 1 to 20 years of age. Data were
      retrieved from parental interviews and questionnaires when the child was 1 and 3
      years of age. At age 20, the participants underwent bitewing radiographic
      examination. Based on the number of approximal caries lesions (Da), stratified
      into initial (Di ) or manifest caries (Dm ) and approximal fillings (Fa), the
      participants were divided into two main groups: those with: (a) 0 Dim Fa (n =
      244) and (b) >0 Dim Fa (n = 250). A subgroup was also created (>=8 Dim Fa; n =
      33). RESULTS: Toothbrushing with fluoride toothpaste at 3 years of age less than
      twice a day (OR 1.6, 95% CI 1.0-2.6) and the participants' mothers' self
      estimation of their oral health care as "less than optimal" were important risk
      factors for developing caries (>0 Dim Fa OR 2.0, 95% CI 1.3-3.1). An interaction
      effect between toothbrushing at 3 years of age less than twice a day and
      consumption of caries risk products > 3 times a day further increased the caries
      experience in young adults (>=8 Dim Fa OR 8.3, 95% CI 1.8-37.8) together with
      maternal anxiety about dental treatment (OR 7.4 95% CI 1.6-34.6). CONCLUSIONS:
      Parental factors in early childhood are associated with caries experience at 20
      years of age.

PMID- 30211441
TI  - What short-term potentiation is and why it may be relevant to obstructive sleep
      apnoea.

PMID- 30211442
TI  - Unenhanced Velocity-Selective MR Angiography (VS-MRA): Initial Clinical
      Evaluation in Patients With Peripheral Artery Disease.
AB  - BACKGROUND: Safe and accurate imaging of the peripheral arterial system is
      important for diagnosis and treatment planning of patients with peripheral artery
      disease (PAD). PURPOSE: To evaluate image quality and diagnostic performance of
      unenhanced magnetic resonance angiography (MRA) based on velocity-selective (VS)
      magnetization preparation (termed VS-MRA). STUDY TYPE: Prospective. POPULATION:
      Thirty-one symptomatic PAD patients underwent VS-MRA. Twenty-four of them
      underwent clinical digital subtraction angiography (DSA) examination, 18.8 +/-
      5.2 days after the MR scans. FIELD STRENGTH/SEQUENCE: 1.5T MRI that included VS
      MRA (homemade research sequence) and phase-contrast flow imaging (clinical
      sequence). ASSESSMENT: Image quality (0: nondiagnostic, 3: excellent) and
      stenosis severity (0: normal, 3: occlusion) of VS-MRA images were assessed
      independently by three reviewers. Arterial signal-to-noise-ratio (SNR) and artery
      to-muscle contrast-to-noise ratio (CNR) were calculated. STATISTICAL TESTS: The
      sensitivity and specificity of VS-MRA were calculated for the detection of
      significant stenosis (>50%) with DSA as the reference standard. Interobserver
      agreement among the three reviewers was evaluated by using Cohen kappa
      statistics. RESULTS: The image quality score of VS-MRA was 2.7 +/- 0.5 for Reader
      1, 2.8 +/- 0.5 for Reader 2, and 2.8 +/- 0.4 for Reader 3; SNR and CNR were 37.8
      +/- 12.5 and 30.5 +/- 11.8, respectively. Segment-based analysis revealed that VS
      MRA had sensitivities of 85.3%, 74.5%, and 78.4%, respectively, for the three
      reviewers, and specificities of 93.5%, 96.8%, and 95.2%. The interobserver
      agreement for the stenosis grading was good, as demonstrated by Cohen kappa
      values of 0.76 (Reader 1 vs. Reader 2), 0.82 (Reader 1 vs. Reader 3), and 0.79
      (Reader 2 vs. Reader 3). DATA CONCLUSION: Unenhanced VS-MRA allows clear
      depiction of the peripheral arteries and accurate stenosis grading, as evidenced
      by high image quality scores and strong agreement with DSA. LEVEL OF EVIDENCE: 2
      Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2018.

PMID- 30211443
TI  - Bowel dysfunction after sigmoid resection for cancer and its impact on quality of
      life.
AB  - BACKGROUND: Several studies have explored functional outcomes after rectal cancer
      surgery, but bowel dysfunction after sigmoid resection for cancer has hardly been
      considered. The aim of this study was to identify the prevalence and pattern of
      bowel dysfunction after resection for sigmoid cancer, and the impact of bowel
      function on quality of life (QoL) by comparison with patients who had polypectomy
      for cancer. METHODS: This was a national cross-sectional study. Data were
      collected from the Danish Colorectal Cancer Group database, and a questionnaire
      regarding bowel function and European Organization for Research and Treatment of
      Cancer (EORTC) QLQ-C30 QoL questionnaire was sent to all Danish colonic cancer
      survivors treated with sigmoid resection or polypectomy between 2001 and 2014.
      RESULTS: A total of 3295 patients (3061 sigmoid resection, 234 polypectomy)
      responded to the questionnaire (response rate 63.8 per cent). Twelve bowel
      symptoms were more prevalent after sigmoid resection, including: excessive
      straining, fragmentation, bloating, nocturnal defaecation, bowel false alarm,
      liquid stool incontinence, incomplete evacuation and sense of outlet obstruction.
      QoL impairment owing to bowel symptoms was reported in 16.6 per cent of patients
      in the resection group and 10.1 per cent after polypectomy (P = 0.008).
      Obstructed defaecation symptoms (ODS) were encountered significantly more often
      after sigmoid resection than following polypectomy (17.9 versus 7.3 per cent; P <
      0.001). In the resection group, patients with ODS had substantial impairment on
      most aspects of QoL assessed by the EORTC QLQ-C30. CONCLUSION: Sigmoid resection
      for cancer is associated with an increased risk of long-term bowel dysfunction;
      obstructed defaecation is prevalent and associated with substantial impairment of
      QoL.

PMID- 30211444
TI  - Metabolic dysfunction in a rat model of early-life scarcity-adversity: Modulatory
      role of cafeteria diet.
AB  - NEW FINDINGS: What is the central question of this study? Early-life adversity is
      associated with increased risk for obesity and metabolic dysfunction. However, it
      is unclear whether obesity and metabolic dysfunction result from coping
      strategies to deal with adversity-related emotional dysregulation, a direct
      programming of systems regulating metabolic function, or a combination of both.
      What is the main finding and its importance? Early-life adversity increases
      vulnerability to later-life obesity and metabolic dysfunction, indicating that
      genetics and adult lifestyle are not the only determinants of obesity and related
      metabolic dysfunction. Moreover, consumption of cafeteria diet exacerbated
      metabolic dysfunction associated with early-life adversity, suggesting that poor
      dietary choices might have a bigger impact in the context of early-life
      adversity. ABSTRACT: Early-life adversity has become recognized as an important
      factor contributing to adult obesity and associated metabolic dysfunction.
      However, it is unclear whether obesity and metabolic dysfunction associated with
      early-life adversity result from coping strategies to deal with adversity-related
      emotional dysregulation, a direct programming of systems regulating metabolic
      function, or a combination. Interestingly, both early-life adversity and later
      life dietary choices affect immune function, favouring pro-inflammatory
      mechanisms that are associated with obesity-related metabolic dysfunction. To
      investigate the unique and/or interactive effects of early-life adversity and
      later-life dietary choices for increased vulnerability to obesity and metabolic
      dysfunction, and specifically the role of the immune system in this
      vulnerability, we combined a naturalistic rat model of early-life scarcity
      adversity with a rat model of obesity, the cafeteria diet. Our results indicate
      that early-life adversity alone induces insulin resistance, reduces pancreatic
      insulin secretion, plasma concentrations of triglycerides and cholesterol, and
      increases fasting glucose and tumour necrosis factor-alpha plasma concentrations.
      Importantly, animals exposed to adverse rearing were more vulnerable to metabolic
      dysregulation associated with the cafeteria diet, given that they consumed more
      energy, showed more severe hepatic steatosis and increased concentrations of the
      pro-inflammatory cytokine interleukin-1beta than normally reared animals fed the
      cafeteria diet. Together, our results suggest that early-life adversity
      negatively programmes physiological systems that regulate metabolic function and
      increases vulnerability to obesity and metabolic dysfunction in adulthood. These
      results highlight the intrinsic relationship between the quality of the early
      postnatal environment and later-life dietary choices on adult health outcomes.

PMID- 30211445
TI  - Assessing regional left ventricular thickening dysfunction and dyssynchrony via
      personalized modeling and 3D wall thickness measurements for acute myocardial
      infarction.
AB  - BACKGROUND: Existing clinical diagnostic and assessment methods could be improved
      to facilitate early detection and treatment of cardiac dysfunction associated
      with acute myocardial infarction (AMI) to reduce morbidity and mortality.
      PURPOSE: To develop 3D personalized left ventricular (LV) models and thickening
      assessment framework for assessing regional wall thickening dysfunction and
      dyssynchrony in AMI patients. STUDY TYPE: Retrospective study, diagnostic
      accuracy. SUBJECTS: Forty-four subjects consisting of 15 healthy subjects and 29
      AMI patients. FIELD STRENGTH/SEQUENCE: 1.5T/steady-state free precession cine MRI
      scans; LGE MRI scans. ASSESSMENT: Quantitative thickening measurements across all
      cardiac phases were correlated and validated against clinical evaluation of
      infarct transmurality by an experienced cardiac radiologist based on the American
      Heart Association (AHA) 17-segment model. STATISTICAL TEST: Nonparametric 2-k
      related sample-based Kruskal-Wallis test; Mann-Whitney U-test; Pearson's
      correlation coefficient. RESULTS: Healthy LV wall segments undergo significant
      wall thickening (P < 0.05) during ejection and have on average a thicker wall
      (8.73 +/- 1.01 mm) compared with infarcted wall segments (2.86 +/- 1.11 mm).
      Myocardium with thick infarct (ie, >50% transmurality) underwent remarkable wall
      thinning during contraction (thickening index [TI] = 1.46 +/- 0.26 mm) as opposed
      to healthy myocardium (TI = 4.01 +/- 1.04 mm). For AMI patients, LV that showed
      signs of thinning were found to be associated with a significantly higher
      percentage of dyssynchrony as compared with healthy subjects (dyssynchrony index
      [DI] = 15.0 +/- 5.0% vs. 7.5 +/- 2.0%, P < 0.01). Also, a strong correlation was
      found between our TI and left ventricular ejection fraction (LVEF) (r = 0.892, P
      < 0.01), and moderate correlation between DI and LVEF (r = 0.494, P < 0.01). DATA
      CONCLUSION: The extracted regional wall thickening and DIs are shown to be
      strongly correlated with infarct severity, therefore suggestive of possible
      practical clinical utility. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J.
      Magn. Reson. Imaging 2018.

PMID- 30211446
TI  - Explaining oral health inequalities in European welfare state regimes: The role
      of health behaviours.
AB  - OBJECTIVE: To assess the extent to which behavioural factors, including those
      related to dental care, account for oral health inequalities in different
      European welfare state regimes. METHODS: Data from the Eurobarometer 2009 survey
      were analysed. Nationally representative samples of dentate adults aged >=45
      years (n = 9979) from 21 European countries classified into the five welfare
      regimes (Scandinavian, Anglo-Saxon, Bismarckian, Southern, Eastern) were
      considered. Inequalities in no functional dentition (having <20 natural teeth) by
      education and occupation were identified using the Relative and Slope Indices of
      Inequality (RII and SII, respectively). The percentage reduction in RII and SII
      was calculated from regression models before and after adjustment for behaviours,
      first one at a time and then all together. RESULTS: Behaviours explained 21.0%
      (95% CI 8.7, 31.4) and 13.1% (95% CI 7.9, 33.2) of educational inequalities in no
      functional dentition (RII) in the Scandinavian and Eastern regimes, respectively.
      For occupational inequalities, the attenuations in RII in these welfare regimes
      were 19.3% (95% CI 7.1, 24.2) and 10.5% (95% CI 3.4, 22.5), respectively.
      Attenuations were weaker and nonsignificant in the Bismarckian, Anglo-Saxon and
      Southern regimes. Among the behaviours analysed, alcohol consumption was
      particularly relevant in explaining inequalities in the Scandinavian regime, and
      this was confirmed in sensitivity analyses through three-way cross-level
      interaction terms in multilevel models. Behaviours related to dental care
      produced similar, consistent attenuations in the Scandinavian and Eastern regimes
      for both socioeconomic indicators. SII findings showed a similar picture.
      CONCLUSION: The role of particular behaviours in explaining oral health
      inequalities could be heterogeneous across European welfare regimes, indicating
      that their importance might be influenced by the general approach to social
      policies.

PMID- 30211448
TI  - Phenotype-genotype relations in facioscapulohumeral muscular dystrophy type 1.
AB  - To determine how much of the clinical variability in facioscapulohumeral muscular
      dystrophy type 1 (FSHD1) can be explained by the D4Z4 repeat array size, D4Z4
      methylation and familial factors, we included 152 carriers of an FSHD1 allele (23
      single cases, 129 familial cases from 37 families) and performed state-of-the-art
      genetic testing, extensive clinical evaluation and quantitative muscle MRI.
      Familial factors accounted for 50% of the variance in disease severity (FSHD
      clinical score). The explained variance by the D4Z4 repeat array size for disease
      severity was limited (approximately 10%), and varied per body region (facial
      muscles, upper and lower extremities approximately 30%, 15% and 3%,
      respectively). Unaffected gene carriers had longer repeat array sizes compared to
      symptomatic individuals (7.3 vs 6.0 units, P = 0.000) and slightly higher Delta1
      methylation levels (D4Z4 methylation corrected for repeat size, 0.96 vs -2.46, P
      = 0.048). The D4Z4 repeat array size and D4Z4 methylation contribute to
      variability in disease severity and penetrance, but other disease modifying
      factors must be involved as well. The larger effect of the D4Z4 repeat array on
      facial muscle involvement suggests that these muscles are more sensitive to the
      influence of the FSHD1 locus itself, whereas leg muscle involvement seems highly
      dependent on modifying factors.

PMID- 30211449
TI  - The society for pediatric and perinatal epidemiologic research: 31st Annual
      meeting summary.

PMID- 30211447
TI  - Ventilatory and integrated physiological responses to chronic hypercapnia in
      goats.
AB  - KEY POINTS: Chronic hypercapnia per se has distinct effects on the mechanisms
      regulating steady-state ventilation and the CO2 /H+ chemoreflex. Chronic
      hypercapnia leads to sustained hyperpnoea that exceeds predicted ventilation
      based upon the CO2 /H+ chemoreflex. There is an integrative ventilatory,
      cardiovascular and metabolic physiological response to chronic hypercapnia.
      Chronic hypercapnia leads to deterioration of cognitive function. ABSTRACT:
      Respiratory diseases such as chronic obstructive pulmonary disease (COPD) often
      lead to chronic hypercapnia which may exacerbate progression of the disease,
      increase risk of mortality and contribute to comorbidities such as cognitive
      dysfunction. Determining the contribution of hypercapnia per se to adaptations in
      ventilation and cognitive dysfunction within this patient population is
      complicated by the presence of multiple comorbidities. Herein, we sought to
      determine the role of chronic hypercapnia per se on the temporal pattern of
      ventilation and the ventilatory CO2 /H+ chemoreflex by exposing healthy goats to
      either room air or an elevated inspired CO2 (InCO2 ) of 6% for 30 days. A second
      objective was to determine whether chronic hypercapnia per se contributes to
      cognitive dysfunction. During 30 days of exposure to 6% InCO2 , steady-state (SS)
      ventilation ( 

PMID- 30211450
TI  - When gain is greater than loss: effects of physical activity on insulin
      sensitivity after short-term inactivity in older subjects.

PMID- 30211451
TI  - Constructing Stable pi-Dimers: Two Parallel Pancake pi-pi Bonds.
AB  - Stable phenalenyl (PLY) radical pi-dimers still play an important role for new
      multifunctional materials owing to their intriguing molecular structure and
      unusual pancake pi-pi bonding mode. Herein, we design a new biphenalenyl
      biradicaloid (1) consisting of two PLYs and one benzene ring linkage tethered by
      single bonds, which presents an open-shell character. Further, three pi-dimers
      (a1, b1, and c1) combined with 1 and conventional biphenalenyl biradicaloid (a,
      b, and c), which are capable of forming two staggered PLY dimers, exhibiting a
      short interlayer distance between the monomers. Interestingly, the analysis of
      the frontier molecular orbital reveals that two bonding orbitals, namely, the two
      highest occupied molecular orbitals (HOMO and HOMO-1) are doubly occupied. The
      results reveal that three pi-dimers display two parallel pancake bonds. Moreover,
      they have small diradical and tetraradical characters, large interaction
      energies, and strong aromaticity, which indicate the stability of these pi
      dimers. The present work creates a new class of strong pancake bonding and might
      be utilized in devising an array of materials.

PMID- 30211453
TI  - Gendered violence and overdose prevention sites: a rapid ethnographic study
      during an overdose epidemic in Vancouver, Canada.
AB  - BACKGROUND AND AIMS: North America's overdose epidemic is increasingly driven by
      fentanyl and fentanyl-adulterated drugs. Supervised consumption sites, including
      low-threshold models (termed overdose prevention sites; OPS), are now being
      debated in the United States and implemented in Canada. Despite evidence that
      gendered and racialized violence shape access to harm reduction among women who
      use drugs (WWUD), this has not been examined in relation to OPS and amid the
      overdose epidemic. This study explores how overlapping epidemics of overdose and
      gendered and racialized violence in Vancouver's Downtown Eastside, one of North
      America's overdose epicenters, impacts how marginalized WWUD experience OPS.
      DESIGN: Qualitative analysis using rapid ethnographic fieldwork. Data collection
      included 185 hours of naturalistic observation and in-depth interviews; data were
      analyzed thematically using NVivo. SETTING: Vancouver, Canada. PARTICIPANTS:
      Thirty-five WWUD recruited from three OPS. MEASUREMENTS: Participants'
      experiences of OPS and the public health emergency. FINDINGS: The rapid onset and
      severity of intoxication associated with the use of fentanyl-adulterated drugs in
      less regulated drug use settings not only amplified WWUD's vulnerability to
      overdose death but also violence. Participants characterized OPS as safer spaces
      to consume drugs in contrast to less regulated settings, and accommodation of
      assisted injections and injecting partnerships was critical to increasing OPS
      access among WWUD. Peer-administered injections disrupted gendered power
      relations to allow women increased control over their drug use; however,
      participants indicated that OPS were also gendered and racialized spaces that
      jeopardized some women's access. CONCLUSION: Although women who use drugs in
      Vancouver, Canada appear to feel that overdose prevention sites address forms of
      everyday violence made worse by the overdose epidemic, these sites remain
      'masculine spaces' that can jeopardize women's access.

PMID- 30211454
TI  - Childhood hearing loss and established risk factors: What is the contribution of
      tobacco exposure prenatally or after birth?

PMID- 30211455
TI  - Synthesis, Mesomorphism, and Photophysics of 2,5-Bis(dodecyloxyphenyl)pyridine
      Complexes of Platinum(IV).
AB  - It has been shown for the first time that the PtIV complex cis-[Pt(N^C-tolpy)2
      Cl2 ] (tolpy=2-(4-tolyl)pyridinyl) can be prepared in a one-pot reaction from K2
      [PtCl4 ], although analogous complexes containing 2,5-bis(4
      dodecyloxyphenyl)pyridine (=HL) could be prepared using existing routes. The
      resulting complexes cis-[Pt(N^C-L)2 Cl2 ] are liquid crystals and small-angle X
      ray scattering suggests formation of a lamellar mesophase. Surprisingly, heating
      [Pt(kappa2 -N^C-L)2 Cl(kappa1 -N^C-LH)] also leads to a mesomorphic compound,
      which results from thermally induced oxidation to cis-[Pt(N^C-L)2 Cl2 ] and what
      is presumed to be another geometric isomer of the same formula. The PtIV
      complexes are quite strongly luminescent in deoxygenated solution, with phi~10 %
      and show vibrationally structured emission spectra, lambdamax (0,0)=532 nm,
      strongly displaced to the red compared to cis-[Pt(N^C-tolpy)Cl2 ]. Long
      luminescence lifetimes of 230 MUs are attributed to a lower degree of metal
      character in the excited state accompanying the extension of conjugation in the
      ligand. There is no significant difference between the emission properties of the
      bromo- and chloro-complexes, in contrast with the known complexes cis-[Pt(N^C
      ppy)X2 ], where the quantum yield for X=Br is some 30 times lower than for X=Cl
      (ppyH=2-phenylpyridine). The lower energy of the excited state in the new
      complexes probably ensures that deactivating LLCT/LMCT states remain thermally
      inaccessible, even when X=Br.

PMID- 30211456
TI  - Sigmatropic Dearomatization/Defluorination Strategy for C-F Transformation:
      Synthesis of Fluorinated Benzofurans from Polyfluorophenols.
AB  - Facile synthesis of fluorinated benzofurans from polyfluorophenols has been
      accomplished by means of a sigmatropic dearomatization/defluorination strategy
      composed of three processes: (1) interrupted Pummerer reaction of ketene
      dithioacetal monoxides with polyfluorophenols followed by [3,3] sigmatropic
      rearrangement, (2) Zn-mediated smooth reductive removal of fluoride from the
      dearomatized intermediate, and (3) acid-promoted cyclization/aromatization.
      Mechanistic investigations revealed important characteristic reactivity of
      polyfluorophenols in the present system. Some of the fluorinated benzofuran
      products were transformed by utilizing the 2-methylsulfanyl moieties.

PMID- 30211458
TI  - A comprehensive next-generation sequencing assay for the diagnosis of
      epidermolysis bullosa.

PMID- 30211459
TI  - Diffuse papulopustular eruption in a newborn.

PMID- 30211460
TI  - Enlarging verrucous plaques in a teenager.

PMID- 30211457
TI  - Development of a Dominant Negative Competence-Stimulating Peptide (dnCSP) that
      Attenuates Streptococcus pneumoniae Infectivity in a Mouse Model of Acute
      Pneumonia.
AB  - Streptococcus pneumoniae (pneumococcus) is a prevalent human pathogen responsible
      for a variety of diseases, including pneumonia, bacteremia, sepsis, meningitis
      and otitis media, with a death toll of >22 000 a year in the United States alone.
      Pneumococcus uses the competence regulon and its associated signaling peptide,
      the competence stimulating peptide (CSP), to initiate its attack on the host and
      establish an infection. In this work, we set out to: 1) develop a pan-group
      quorum sensing inhibitor that could effectively interact with both the
      pneumococcus ComD1 and ComD2 receptors; and 2) evaluate the utility of dominant
      negative CSPs (dnCSPs) in attenuating pneumococcus infectivity. Our results
      highlight the potential of inhibiting the competence regulon as a therapeutic
      approach to combat pneumococcus infections.

PMID- 30211461
TI  - A hair out of place in a 6-year-old boy.

PMID- 30211463
TI  - Patient Perspectives: What is Diaper Rash?

PMID- 30211462
TI  - Response to "Doing the math: A simple approach to topical timolol dosing for
      infantile hemangiomas".

PMID- 30211464
TI  - An infant with a capillary malformation on the lower lip.

PMID- 30211465
TI  - Red-brown macules in a linear distribution on the arm.

PMID- 30211466
TI  - Comment on "Excellent response to ustekinumab in a 9-year-old girl with severe
      psoriasis".

PMID- 30211468
TI  - Comment on "Doing the math: A simple approach to topical timolol dosing for
      infantile hemangiomas".

PMID- 30211469
TI  - Child with flagellate skin eruptions.

PMID- 30211470
TI  - Skin lesions in a 5-year-old boy with recent unusual course of pneumonia.

PMID- 30211471
TI  - A rapidly-growing, exophytic papule on the nose of a 9-year-old Native American
      boy.

PMID- 30211472
TI  - Pulmonary metastasectomy: analysis of survival and prognostic factors in 243
      patients.
AB  - BACKGROUND: Pulmonary metastases are a sign of advanced malignant disease.
      Interdisciplinary management of metastatic cancer mandates the consideration of
      all treatment options, and in selected patients pulmonary metastasectomy can be
      performed with curative intent. This study aims to analyze the prognostic factors
      associated with survival and optimize the selection of surgical candidates. The
      sarcoma subset analysis aims to examine the role of multiple repeat resections
      for pulmonary metastatic recurrence. METHODS: A total of 243 patients were
      analyzed in this retrospective cohort study. Overall survival was estimated using
      Kaplan-Meier analysis. Univariate analyses with log-rank tests and multivariate
      analysis with Cox proportional hazards model were undertaken to determine the
      independent prognostic factors for survival. RESULTS: Multivariate analyses
      identified germ cell cancer (P = 0.01) and a disease-free interval of >36 months
      (P = 0.006) as significant independent prognostic factors for improved survival,
      whilst synchronous metastases (P = 0.04), multiple metastases (P = 0.005) and
      incomplete resection (P < 0.001) were identified as significantly poor prognostic
      factors. Subset analyses identified that >=2 repeat resections within the sarcoma
      cohort was associated with an increased median survival of 63.5 months (P =
      0.04). CONCLUSION: In selected patients, pulmonary metastasectomy can be
      performed with curative intent and have associated long-term survival benefits.
      Patients presenting with recurrent sarcoma pulmonary metastases should be
      considered for repeat metastasectomy.

PMID- 30211473
TI  - Surgical treatment of otitis media with effusion in Maori children.
AB  - BACKGROUND: This study aimed to compare the incidence and outcomes of Maori and
      non-Maori children with otitis media with effusion who underwent myringotomy plus
      ventilation tube insertion (MVTI). METHODS: De-identified extraction of Auckland
      District Health Board (ADHB) morbidity records belonging to all children who
      underwent an MVTI procedure between January 1996 and June 2016 at Starship
      Children's Hospital was performed. Demographic, procedural and outcome data were
      analysed. RESULTS: A total of 11 941 children aged less than 10 years underwent
      at least one MVTI procedure in the Auckland region from January 1996 to June
      2016. Of those, 2387 (20%) were Maori and 9554 (80%) were non-Maori. There was no
      difference in gender, age, length of stay, 30-day readmissions or complications
      between Maori and non-Maori at index or subsequent surgeries. Maori were not more
      likely than non-Maori to require subsequent MVTI (P = 0.13). There was no
      difference between Maori and non-Maori rates of having MVTI alone (P = 0.11) or
      MVTI with adenoidectomy +/- tonsillectomy (P = 0.61). CONCLUSIONS: Some
      epidemiological evidence suggests that Maori have a higher incidence of middle
      ear disease in the community. However, this study indicates that there is no
      difference in the post-operative course between Maori and non-Maori children.

PMID- 30211474
TI  - A bidirectional corneoconjunctival transposition for the treatment of feline
      corneal sequestrum.
AB  - A case is presented of a 1-year-old Persian cat with a corneal sequestrum treated
      with a bidirectional corneoconjunctival transposition. The size of this lesion
      precluded use of a traditional corneoconjunctival transposition. At the time of
      writing, the patient maintained a clear visual axis with minimal scarring and no
      recurrence 6 months post-operatively. This report describes a novel surgical
      technique used to successfully treat a large feline corneal sequestrum.

PMID- 30211475
TI  - Encouragements for the Use of Microwaves in Industrial Chemistry.
AB  - Microwave travels at the speed of light, and transfers energy solely to
      materials. This holds great promise for energy conservation in industrial
      processes. However, due to differences with common heating principles, and
      misunderstanding of the correct way to handle them, the effectiveness of
      microwaves has been underestimated, and development of technologies using
      microwaves often stops due to this. This paper has focused on the use of
      microwave heating for organic/polymer synthesis, specifically for a highly
      effective condensation reaction and for use with ionic reactants. In addition to
      covering the process of ascertaining which reactions are suitable for the
      application of microwave heating, and introducing studies on scaling these up,
      this paper covers points of caution, especially those relating to the all
      important measurement/control of temperature. Based on their accumulation of
      expertise in the area, the authors present the design for equipment/plants for
      industrial use and introduce their research into the practical application of
      such technology.

PMID- 30211476
TI  - Twisted intussusception: a case report.

PMID- 30211477
TI  - Punctal stenosis in 6 dogs following the long-term use of topical neomycin
      polymyxin B-dexamethasone.
AB  - Six dogs were diagnosed with punctal stenosis following the long-term use of
      topical neomycin-polymyxin B-dexamethasone (NPD). All patients were initially
      presented for ophthalmic diseases requiring ongoing anti-inflammatory therapy.
      Five of the 6 dogs had previously or concurrently been treated with topical anti
      inflammatory medications other than NPD. One patient exclusively received topical
      NPD prior to the diagnosis of punctal stenosis. The onset of punctal stenosis
      following therapy with NPD was variable among patients, ranging from 4 months to
      over 1 year. Diagnosis of punctal stenosis was made based upon the presence of
      epiphora and visualization of fibrotic tissue over the nasolacrimal puncta.

PMID- 30211479
TI  - Rapidly growing verrucous axillary tumors, multiple erosions, pustules, and
      cheilitis.

PMID- 30211478
TI  - Totally-laparoscopic versus laparoscopic-assisted low anterior resection for
      rectal cancer: are outcomes different?
AB  - BACKGROUND: Laparoscopic low anterior resection for rectal cancer has superior
      short-term benefits compared to open surgery. When operative conditions do not
      favour a totally-laparoscopic (TL) approach, a hybrid operation can be performed.
      In this laparoscopic-assisted (LA) approach, mobilization and vessel ligation are
      performed laparoscopically, with total mesorectal excision and distal transection
      performed either partially or totally in an extra-corporeal fashion. We compared
      short-term post-operative and oncological outcomes of both approaches. METHODS: A
      prospectively collected database of patients who underwent laparoscopic low
      anterior resection for rectal cancer between January 2009 and December 2014 was
      retrospectively analysed. Demographics, post-operative and oncological outcomes
      were compared. RESULTS: Of 174 patients, 97 were completed by TL, 62 by LA and
      the remaining 15 were converted to open. Baseline demographics were similar. LA
      group compared to TL group had bulkier rectal cancers (6.75 cm3 versus 4.50 cm3 ,
      P = 0.04) which were lower (6 cm versus 7 cm from anal verge, P = 0.02). They
      were of a more advanced tumour grade and had greater incidence of lymphovascular
      invasion. Yet, post-operative outcomes such as time to diet, pain scores,
      hospitalization duration, wound-related and anastomotic complications, 30-day
      morbidity and mortality were similar. There was no difference in oncological
      adequacy, including circumferential resection margins, distal margins, lymph node
      harvest and 2-year local recurrence rates. CONCLUSION: Laparoscopic-assisted low
      anterior resection enables minimally invasive rectal surgery to be performed
      despite unfavourable tumour factors and technical challenges; and compares
      favourably with TL approach in terms of short-term outcomes and oncological
      safety.

PMID- 30211480
TI  - The prognosis of mid-range ejection fraction heart failure: a systematic review
      and meta-analysis.
AB  - AIMS: Mid-range ejection fraction is a new entity of heart failure (HF) with
      undetermined prognosis till now. In our systematic review and meta-analysis, we
      assess the mortality and hospitalization rates in mid-range ejection fraction HF
      (HFmrEF) and compare them with those of reduced ejection fraction heart failure
      (HFrEF) and preserved ejection fraction HF (HFpEF). METHODS AND RESULTS: We
      conducted our search in March 2018 in the following databases for relevant
      articles: PubMed, CENTRAL, Google Scholar, Web of Science, Scopus, NYAM, SIEGLE,
      GHL, VHL, and POPLINE. Our primary endpoint was assessing all-cause mortality and
      all-cause hospital re-admission rates in HFmrEF in comparison with HFrEF and
      HFpEF. Secondary endpoints were the possible causes of death and hospital re
      admission. Twenty-five articles were included in our meta-analysis with a total
      of 606 762 adult cardiac patients. Our meta-analysis showed that HFmrEF had a
      lower rate of all-cause death than had HFrEF [relative risk (RR), 0.9; 95%
      confidence interval (CI), 0.85-0.94]. HFpEF showed a higher rate of cardiac
      mortality than did HFmrEF (RR, 1.09; 95% CI, 1.02-1.16). Also, HFrEF had a higher
      rate of non-cardiac mortality than had HFmrEF (RR, 1.31; 95% CI, 1.22-1.41).
      CONCLUSIONS: We detected a significant difference between HFrEF and HFmrEF
      regarding all-cause death, and non-cardiac death, while HFpEF differed
      significantly from HFmrEF regarding cardiac death.

PMID- 30211481
TI  - Age-associated changes in the equine flash visual evoked potential.
AB  - OBJECTIVE: To investigate age-associated changes of flash visual evoked
      potentials (FVEPs) in sedated horses. ANIMAL STUDIED: Twenty-eight clinically
      healthy Standardbred Warmblooded trotters, aged 36 hours to 28 years. PROCEDURES:
      Light-adapted FVEPs and FERGs were recorded (An-vision RETIport, Roland-consult,
      Germany) in response to flash stimuli. Sedation was obtained using alpha-2
      agonists intravenously. Akinesia of the eyelids was induced and pupils were
      dilated. RESULTS: Reproducible FVEPs and FERGs were readily recorded from all
      foals and horses. The FVEP waveform included up to four positive components (P1
      P5) and two negative components (N1 and N2) and FVEP waveform morphology was
      similar across all age groups. Some differences in peak times and amplitudes
      associated with increasing age were observed. FVEP amplitudes recorded from
      newborn foals were well above the amplitudes observed in normal adult horses and
      FVEP peak times were somewhat shorter. In adult horses, a significant increase in
      P4 peak time and a gradual decrease in amplitudes, mainly for N2P4, were seen
      across the life-span. CONCLUSIONS: The overall equine FVEP waveform was similar
      across the normal life-span of the horse in our cross-sectional study. We found
      that the visual system of the foal seems to be well developed already at birth.
      Furthermore, our results showed a decrease in amplitudes and increase in some
      peak times with increasing age. We recommend that age-matched controls should be
      used when evaluating foals and young horses in clinical practice, whereas horses
      over the age of three years can be compared to other adult horses.

PMID- 30211482
TI  - Mixed and Matched Metallo-Nanotexaphyrin for Customizable Biomedical Imaging.
AB  - The discovery and synthesis of multifunctional organic building blocks for
      nanoparticles have remained challenging. Texaphyrin macrocycles are
      multifunctional, all-organic compounds that possess versatile metal-chelation
      capabilities and unique theranostics properties for biomedical applications.
      Unfortunately, there are significant difficulties associated with the synthesis
      of texaphyrin-based subunits capable of forming nanoparticles. Herein, the
      detailed synthesis of a texaphyrin-phospholipid building block is reported via a
      key 1,2-dinitrophenyl-phospholipid intermediate, along with stable chelation of
      two clinically relevant metal ions into texaphyrin-lipid without compromising
      their self-assembly into texaphyrin nanoparticles or nanotexaphyrin. A
      postinsertion methodology to quantitatively insert a variety of metal-ions into
      preformed nanotexaphyrins is developed and employed to synthesize a structurally
      stable, mixed 111 indium-manganese-nanotexaphyrin for dual modal single-photon
      emission computed tomography (SPECT) and magnetic resonance imaging (MRI). In
      vivo dual SPECT/MRI imaging of 111 In-Mn-nanotexaphyrins in an orthotopic
      prostatic PC3 mouse model demonstrates complementary signal enhancement in the
      tumor with both modalities at 22 h post intravenous administration. This result
      highlights the utility of hybrid metallo-nanotexaphyrins to achieve sensitive and
      accurate detection of tumors by accommodating multiple imaging modalities. The
      power of this mixed and matched metallo-nanotexaphyrin strategy can be unleashed
      to allow a diverse range of multifunctional biomedical imaging.

PMID- 30211483
TI  - Identification of Changing Ribosome Protein Compositions using Mass Spectrometry.
AB  - The regulatory role of the ribosome in gene expression has come into sharper
      focus. It has been proposed that ribosomes are dynamic complexes capable of
      changing their protein composition in response to environmental stimuli. MS is
      applied to identify quantitative changes in the protein composition of S.
      cerevisiae 80S ribosomes in response to different environmental stimuli. Using
      quantitative MS, it is found that the paralog yeast ribosomal proteins RPL8A
      (eL8A) and RPL8B (eL8B) change their relative proportions in the 80S ribosome
      when yeast is switched from growth in glucose to glycerol. By using yeast
      genetics and polysome profiling, it is shown that yeast ribosomes containing
      either RPL8A or RPL8B are not functionally interchangeable. The quantitative
      proteomic data support the hypothesis that ribosomes are dynamic complexes that
      alter their composition and functional activity in response to changes in growth
      or environmental conditions.

PMID- 30211484
TI  - The use of the NICE ten step model to conduct an oral health needs assessment in
      South Yorkshire and Bassetlaw.
AB  - The Health and Social Care Act 2012 created a new commissioning framework for the
      provision of health, social care and public health in England (UK Government,
      2012). NHS England became the sole commissioner for all NHS dental services,
      including primary, secondary and unscheduled dental care. Local authorities
      became responsible for public health, epidemiological surveys, improving the oral
      health of their communities and for commissioning oral health improvement
      services including water fluoridation (NHS Bodies and Local Authorities
      (Partnership Arrangements, Care Trusts, Public Health and Local Healthwatch)
      Regulations (SI 2012/3094)). At the time this needs assessment was conducted, NHS
      South Yorkshire and Bassetlaw Area Team commissioned all the NHS dental services
      in the local authority areas of Barnsley, Doncaster, Rotherham, Sheffield and
      Bassetlaw. The dental Local Professional Network provided clinical and public
      health input to the commissioning process through its annual work plan. However,
      there was no up to date information on local oral health needs and how these
      needs were being met by NHS dental services, hence it was difficult to determine
      what were the local commissioning priorities.

PMID- 30211485
TI  - Timely identification of patients with frailty at the 'front door' of acute
      hospitals.
AB  - Early identification of frailty at the front door of the acute hospital is vital
      to allow rapid comprehensive geriatric assessment and care pathway development in
      the most appropriate location. This article discusses the importance of
      developing robust processes to enable early identification and management of
      frailty in the acute hospital. It also highlights the benefits of developing a
      dynamic team of professionals at the front door of the acute hospital who are
      effectively trained to undertake comprehensive assessment. Effective care
      planning for older people with frailty requires meticulous coordination through
      collaboration across health and social care and this is demonstrated using an
      effective model which has been developed in a district general hospital in
      Scotland.

PMID- 30211486
TI  - Managing chronic spontaneous urticaria (hives) in primary care.
AB  - Chronic spontaneous urticaria is characterised by the spontaneous appearance of
      hives or wheals, and/or angioedema, lasting for at least six weeks. The condition
      may be associated with significant physical and emotional burden for patients.
      Nurses have an important role in the differential diagnosis of chronic
      spontaneous urticaria, assessing patients' quality of life, providing advice on
      non-pharmacological measures, monitoring the patient's response to treatment, and
      referring the patient for specialist care, where appropriate. This article
      describes the presentation, diagnosis and management of chronic spontaneous
      urticaria in primary care.

PMID- 30211487
TI  - Safeguarding of vulnerable adults training: assessing the effect of continuing
      professional development.
AB  - AIM: This article provides an insight into the effect of safeguarding of
      vulnerable adults continuing professional development (SOVA-CPD) training for
      nurses. METHOD: 51 participants were recruited from three different cohorts of
      SOVA-CPD training that had been delivered in east England. A 50-item
      questionnaire was designed to gather participants' views on their acquisition of
      knowledge and skills, and perceived changes in practice, and to allow them to
      describe how they have changed how they work due to the training. RESULTS:
      Participants agreed overwhelmingly that the SOVA-CPD had enhanced their
      competency and skills so that their patients' care could improve. However,
      despite the benefits that some participants described, the potential positive
      effects of SOVA-CPD were curtailed by the challenges participants experienced in
      making changes in their practice settings. CONCLUSION: The study highlights
      several benefits of SOVA-CPD for nurses, including the benefits to patient care
      of a CPD learning environment for practitioners. It suggests that employers
      should provide environments in which staff who have undertaken SOVA-CPD can
      trigger and sustain changes to improve patient care.

PMID- 30211488
TI  - Giving voice to adults with intellectual disabilities and experience of mental
      ill-health: validity of a psychosocial approach.
AB  - BACKGROUND: Mental ill-health is more prevalent among adults with intellectual
      disabilities (ID) than in the wider population. An interest in the mental health
      needs of people with ID has developed in recent decades, which corresponds with
      implementation of the health and social policy of deinstitutionalisation. Much
      clinical and research activity has focused on how such mental health needs may be
      addressed. The literature indicates that the views of people with ID concerning
      their mental health care have received limited attention. AIM: To describe the
      adaption of a psychosocial research approach ( Hollway and Jefferson 2000 , 2013
      ), and discuss the methodological challenges encountered in enabling adults with
      intellectual disabilities (ID) to express their views and be actively involved in
      producing knowledge about their experiences of care and support as service users
      with diagnosed mental health needs. DISCUSSION: A considerable advantage of the
      interview format of this psychosocial approach was the opportunities it afforded
      participants to recount their personal stories. This is contrary to the question
      and-answer technique of interviewing, which can suppress the stories of
      interviewees. In such structured approaches, the interviewer establishes the
      boundaries and usually maintains control over the production of data. CONCLUSION:
      Undertaking two research interviews with participants, analysis of the entire
      material regarding individual participants, and undertaking comparative analysis
      of data relating to all participants provided a system for checking consistency.
      This approach therefore provides a valid method for enabling the participation of
      people with ID. IMPLICATIONS FOR PRACTICE: The approach used is congruent with
      the requirement for the subjectivities of researchers - and those being
      researched - to be acknowledged, which is central to disability research. It is
      also compatible with person-centred planning and coproduction, which are central
      to contemporary ID nursing practice.

PMID- 30211489
TI  - ECMO for Severe Acute Respiratory Distress Syndrome.

PMID- 30211490
TI  - ECMO for Severe Acute Respiratory Distress Syndrome.

PMID- 30211491
TI  - ECMO for Severe Acute Respiratory Distress Syndrome.

PMID- 30211492
TI  - Lung Cancer with a High Tumor Mutational Burden.

PMID- 30211494
TI  - On the Move.

PMID- 30211495
TI  - Dry Eye.

PMID- 30211493
TI  - Dry Eye.

PMID- 30211496
TI  - Dry Eye.

PMID- 30211497
TI  - Respirators-Mandatory or Voluntary, Know the Difference: It's more important than
      ever for employers to stay focused on OSHA regulations-not only to avoid
      citations and costly fines, but also to protect the organization's most valuable
      asset, the employees.

PMID- 30211498
TI  - Pembrolizumab plus Chemotherapy in Lung Cancer.

PMID- 30211499
TI  - Pembrolizumab plus Chemotherapy in Lung Cancer.

PMID- 30211500
TI  - Workplace Stretching Programs: They are another tool in the musculoskeletal
      disorder (MSD) prevention toolbox.

PMID- 30211501
TI  - Pembrolizumab plus Chemotherapy in Lung Cancer.

PMID- 30211502
TI  - Debunking the Top Three Myths About Industrial Machine Safeguarding: Lack of
      understanding of OSHA machine guard regulations continues to make machine
      safeguarding one of OSHA's Top 10 violations.

PMID- 30211503
TI  - Finding the Right Machine Safety Partner for Your Company: Here's what EHS pros
      need to know about machine safeguarding.

PMID- 30211504
TI  - Fit Makes the Difference: BLS reported there were 23,730 eye injuries requiring
      time away from work in 2014, or 6 percent of all lost-time cases in private
      industry and state and local government employment.

PMID- 30211505
TI  - Essential Elements of Worker Protection: The more information you have about your
      own organization and workforce, the better the insight into how to reduce hazards
      to an acceptable level.

PMID- 30211507
TI  - Legalized Marijuana-The Popular Perspective: As a safety manager, an HR director,
      or a company executive, remaining confused and silent toward the issue of legal
      marijuana may prove to be a very costly mistake for you and your company.

PMID- 30211506
TI  - NIOSH Proposes RELs for Diacetyl and 2,3-Pentanedione: The agency recommends a
      recommended exposure limit of 5 ppb for diacetyl as a time-weighted average for
      up to 8 hours/day during a 40-hour work week and a short-term exposure limit of
      25 parts per billion for a 15-minute time period.

PMID- 30211508
TI  - A Policy Option to Enhance Access and Affordability for Medicare's Low-Income
      Beneficiaries.
AB  - Issue: An estimated 40 percent of low-income Medicare beneficiaries spend 20
      percent or more of their incomes on premiums and health care costs. Low-income
      beneficiaries with multiple chronic conditions or high need are at particular
      risk of financial hardship. High cost burdens reflect Medicare premiums and cost
      sharing, gaps in benefits, and limited assistance. Existing policies to help
      people with low incomes are fragmented - meaning that beneficiaries apply
      separately, sometimesto different offices - and require Medicare beneficiaries to
      navigate complex applications. Goals: With the goal of enhancing access and
      affordability for people vulnerable due to low incomes and poor health, this
      issue brief proposes a policy that would reduce Medicare's cost-sharing and
      premiums for beneficiaries with incomes below 150 percent of the federal poverty
      level. Methods: Profile current cost burdens by income groups and assess the
      potential impact of a policy to expand cost-sharing and premium assistance using
      the 2012 Medicare Current Beneficiary Survey projectedto 2016. Results and
      Conclusion: The policy described could help 8.1 million low-income beneficiaries,
      significantly lowering their risk of high cost burdens. It also could simplify
      the administration of assistance provided to these enrollees.

PMID- 30211509
TI  - How to Choose Gloves to Protect Against Arc Flash: You don't want to wear gloves
      that will burn, catch fire or not protect from heat. Beyond sustained injuries,
      ignoring the need for proper electrical PPE can result in huge fines.

PMID- 30211510
TI  - Hands-On Safety: Hand usage can affect cumulative trauma soft-tissue issues in
      the arms, neck, shoulders, and back.

PMID- 30211511
TI  - A Safety Plan for a Silent Killer: Following a five-step plan helps you design a
      program to protect your team from sudden cardiac arrest.

PMID- 30211512
TI  - Visualizing a Comprehensive Safety Excellence Strategic Framework: Most
      organizations, both at the corporate and local site level can only effectively
      manage and execute against four to five major priorities per year.

PMID- 30211514
TI  - Beyond Supercharging: How Do You Actually Upgrade Safety Actions? Two methods for
      change may appear to have comparable components, even be called by similar terms,
      but may actually be done very differently. And everyone knows the difference.

PMID- 30211515
TI  - Health Insurance Marketplaces: Issuer Participation and Premium Trends in Rural
      Places, 2018.
AB  - Purpose: Since 2014, when the Health Insurance Marketplaces (HIMs) authorized by
      the Patient Protection and Affordable Care Act (PPACA) were implemented,
      considerable premium changes have been observed in the marketplaces across the 50
      states and the District of Columbia. This policy brief assesses the changes in
      average HIM plan premiums from 2014 to 2018, before accounting for subsidies,
      with an emphasis on the widening variation across rural and urban places,
      providing information during Congressional debates on the future of the program.
      Key Findings: (1) Insurance issuers reduced HIM participation across both rural
      and urban places (with 1.7 and 2.2 issuers, respectively), both in states that
      expanded Medicaid under the PPACA and in non-expansion states. (2) The average
      adjusted premium (before premium subsidy) continues to rise across all of the
      above categories, and the gap has widened between the 32 Medicaid expansion and
      19 non-expansion states. Average premiums in rural counties are higher than
      average premiums in urban counties in both expansion and non-expansion states (by
      $43 per month and $27 per month, respectively). (3) Prior trends of lower premium
      changes at greater population densities are no longer observed in the 2018 data.
      (4) In 2018, 1,581 counties (52 perent) have one participating insurance issuer.
      Nationwide, 42 percent of all urban counties and 55 percent of all rural counties
      only have one issuer.

PMID- 30211517
TI  - On the Move.

PMID- 30211516
TI  - Spread of Medicare Accountable Care Organizations in Rural America.
AB  - Purpose: This RUPRI Center data report describes Medicare accountable care
      organization (ACO) growth in non-metropolitan U.S. counties from 2016 to 2017.
      This data report, which includes data through December 2017, follows a similar
      analysis released in October 2016 that described ACO trends from 2013 to 2015.
      Key Findings: The following findings are based on activity through 2017: (1)
      Medicare ACOs operate (an ACO provider is present) in 60.3 percent of all
      nonmetropolitan counties, up from 41.8 percent in 2016, (2) As of December 2017,
      no nonmetropolitan ACOs were participating in ACO models that included downside
      risk (meaning they are liable for expenditures exceeding a benchmark).

PMID- 30211518
TI  - The Dangers of Heat Stress: Fans improve safety during the hottest months of the
      year.

PMID- 30211519
TI  - Ear Plug Selection and Fitting Best Practices: Fit-testing of hearing protection
      now allows a worker to try various hearing protectors to determine which type is
      most suitable.

PMID- 30211520
TI  - Alleviating the Risk from Above: Hazards overhead are a concern for workers in
      many industries, notably upstream oil and gas and construction.

PMID- 30211521
TI  - Staying on Top of Hazmat Training Requirements: The key standard for working with
      hazardous chemicals is 29 CFR 1910.1200, the revised Hazard Communication
      Standard, which has been aligned with the Globally Harmonized System of
      Classification and Labeling of Chemicals.

PMID- 30211522
TI  - Beyond Compliance: Specifying Reliable Flame Resistant Workwear: Know what you
      are truly buying: The AR/FR fabric in workwear is the single largest factor in
      determining the garment's protection level, comfort, and overall value.

PMID- 30211523
TI  - The Need for a Shield Against Steel: It is important to understand the entire
      spectrum of risks steelworkers are exposed to and consider multifunctional PPE
      alternatives to protect against each hazard.

PMID- 30211524
TI  - Maintaining Fire Compliant Openings: While most people using institutional and
      commercial buildings worry most about security issues these days, fires strike
      far more often than those types of emergencies.

PMID- 30211525
TI  - Fire Alarm or Test? Let's work on designing and conducting tests and drills so
      that alarms are for emergencies and the employees respond in a safe and proper
      manner.

PMID- 30211526
TI  - The National Movement in Ladder Safety: New, safer designs will help prevent
      those accidents when we are in a hurry or forget the basic rules.

PMID- 30211527
TI  - pH-Controlled Drug Release by Diffusion through Silica Nanochannel Membranes.
AB  - We report in this work the fabrication of a flow-through silica nanochannel
      membrane (SNM) for controlled drug release applications. The ultrathin SNM
      consists of parallel nanochannels with a uniform diameter of ~2.3 nm and a
      density of 4 * 1012 cm-2, which provide simultaneously high permeability and size
      selectivity toward small molecules. The track-etched porous polyethylene
      terephthalate film premodified with silane on its surface was used to support the
      ultrathin SNM via irreversible covalent bond formation, thus offering mechanical
      strength, flexibility, and stability to the ultrathin SNM for continuous and long
      term use. Alkylamines were subsequently grafted onto the SNM surface to modulate
      the "on" and "off" state of nanochannels by medium pH for controlled drug
      release. Thiamphenicol glycinate hydrochloride (TPG), an intestinal drug, was
      studied as a model to permeate through an ultrathin SNM in both simulated gastric
      fluid (pH = 1.2) and simulated intestinal fluid (pH = 7.5). The release in the
      latter case was 178 times faster than that in the former. Moreover, a nearly zero
      order constant release of TPG via single-file diffusion was achieved up to 24 h,
      demonstrating the feasibility of sustained and continuous release of small
      molecule drugs in a pH-controlled manner.

PMID- 30211528
TI  - Ultrahigh Metal-Organic Framework Loading and Flexible Nanofibrous Membranes for
      Efficient CO2 Capture with Long-Term, Ultrastable Recyclability.
AB  - In the global transition to a sustainable low-carbon economy, CO2 capture and
      storage technology plays a key role in reducing emissions. Metal-organic
      frameworks (MOFs) are crystalline materials with ultrahigh porosity, tunable pore
      size, and rich functionalities, holding the promise for CO2 capture. However, the
      intrinsic fragility and depressed processability of MOF crystals make the
      fabrication of the flexible MOF nanofibrous membrane (NFM) rather challenging.
      Herein, we demonstrate an effective strategy for the versatile preparation of
      self-supported and flexible HKUST-1 NFM with ultrahigh HKUST-1 loading (up to 82
      wt %) and stable and uniform HKUST-1 growth through the combination of
      electrospinning, multistep seeded growth, and activation process. The loading
      rate of MOF is the highest level among the reported analogues. Significantly, the
      HKUST-1 NFM exhibits a prominent CO2 adsorption capacity of 3.9 mmol g-1, good
      CO2/N2 selectivity, and remarkable recyclability. The CO2 capacity retains ~95%
      (3.7 mmol g-1) of the initial value after 100 adsorption-desorption cycles,
      indicating that the HKUST-1 NFM has long-term and ultrastable recyclability and a
      significant practical value. Thus, the low-cost and scalable production pathway
      is able to convert MOF particles into self-supported and flexible NFMs, and
      thereby, they are better applied to the efficient postcombustion CO2 capture.

PMID- 30211529
TI  - Selective Growth of Interface Layers from Reactions of Sc(MeCp)2(Me2pz) with
      Oxide Substrates.
AB  - The transformation of an oxide substrate by its reaction with a chemical
      precursor during atomic layer deposition (ALD) has not attracted much attention,
      as films are typically deposited on top of the oxide substrate. However, any
      modification to the substrate surface can impact the electrical and optical
      properties of the device. We demonstrate herein the ability of a precursor to
      react deep within an oxide substrate to form an interfacial layer that is
      distinct from both the substrate and deposited film. This phenomenon is studied
      using a scandium precursor, Sc(MeCp)2(Me2pz) (1, MeCp = methylcyclopentadienyl,
      Me2pz = 3,5-dimethylpyrazolate), and five oxide substrates (SiO2, ZnO, Al2O3,
      TiO2, and HfO2). In situ Fourier transform infrared (FTIR) spectroscopy shows
      that at moderate temperatures (~150  degrees C) the pyrazolate group of 1 reacts
      with the surface hydroxyl groups of OH-terminated SiO2 substrates. However, at
      slightly higher temperatures (>=225  degrees C) typically used for the ALD of
      Sc2O3, there is a direct reaction between 1 and the SiO2 layer, in addition to
      chemisorption at the surface hydroxyl groups. This reaction is sustained by
      sequential exposures of 1 until an ~2 nm thick passivating interface layer is
      formed, indicating that 1 reacts with oxygen derived from SiO2. A shift of the Si
      2p core level position, measured by ex situ X-ray photoelectron spectroscopy, is
      consistent with the formation of a ScSi xO y layer. Similar observations are made
      following the exposure of a ZnO substrate to 1 at 275  degrees C. In contrast,
      Al2O3, TiO2, and HfO2 substrates remain resistant to reaction with 1 under
      similar conditions, except for a surface reaction occurring in the case of TiO2.
      These striking observations are attributed to the differences in the
      electrochemical potentials of the elements comprising the oxide substrates to
      that of scandium. Precursor 1 can react with SiO2 or ZnO substrates, since the
      constituent elements of these oxides have less-negative electrochemical
      potentials than do aluminum, titanium, and hafnium. Additionally, Sc2O3 and
      surface carbonates are deposited on all substrates by gas-phase reactions between
      1 and residual water vapor in the reactor. The extent of gas-phase reactions
      contributing to film growth is governed by the relative pressure of water vapor
      in the presence of 1. These results suggest caution when using very reactive,
      oxophilic precursors such as 1 to avoid misinterpreting unconventional film
      deposition as that resulting from a standard ALD process.

PMID- 30211530
TI  - Insight into Nanoscale Network of Spray-Dried Polymeric Particles: Role of
      Polymer Molecular Conformation.
AB  - Poly(lactic- co-glycolic acid) (PLGA) microparticles represent a promising
      formulation approach for providing steady pharmacokinetic/pharmacodynamic
      profiles of therapeutic drugs for a long period. Understanding and controlling
      the supramolecular structure of PLGA microparticles at a molecular level is a
      prerequisite for the rational design of well-controlled, reproducible sustained
      release profiles. Herein, we reveal the role of PLGA molecular conformation in
      particle formation and drug release. The nanoscale network of PLGA microparticles
      spray-dried using the solvents with distinct polarities was investigated by using
      NMR and neutron scattering. By employing chemometric method, we further
      demonstrate the evolution of nanoscale networks in spray-dried PLGA
      microparticles upon water absorption. Our results indicate that PLGA molecules
      form more chain entanglements during spray drying when using the solvents with
      low polarity, where PLGA molecule adopts a more flexible, extended conformation,
      resulting in the network being more resistant to water absorption in spray-dried
      PLGA microparticles. This work underlines the role of PLGA molecular conformation
      in controlling formation and evolution of nanoscale network of spray-dried PLGA
      microparticles and will have important consequences in achieving customized drug
      release from the PLGA microparticles.

PMID- 30211531
TI  - Polyhedral Oligomeric Silsesquioxane (POSS)-Based Cationic Conjugated
      Oligoelectrolyte/Porphyrin for Efficient Energy Transfer and Multiamplified
      Antimicrobial Activity.
AB  - Cationic quaternary ammonium (QA) groups and reactive oxygen species as two main
      approaches for antibacterial study have been intensively studied. Herein, we
      report a multifunctional antimicrobial agent (porphyrin-POSS-OPVE, PPO), which
      combines bacterial membrane intercalation, high density of local QA groups,
      efficient energy transfer, significantly reduced aggregation, and high water
      solubility into one single molecule. The light-harvesting PPO contains multiple
      donor-absorbing arms (oligo( p-phenylenevinylene) electrolytes, OPVEs) on its
      globular periphery and a central porphyrin acceptor in the core by using three
      dimensional nanocages (polyhedral oligomeric silsesquioxanes, POSSs) as bridges.
      The antiaggregation ability of POSS and the highly efficient energy transfer from
      multiple OPVE arms to porphyrin could greatly amplify singlet oxygen generation
      in PPO. Particularly, OPVEs with QA terminal chains were able to intercalate into
      Escherichia coli membranes, which facilitated 1O2 diffusion and bacterial cell
      membrane disintegration by QA groups. The increased local cationic QA charges in
      OPVE arms can also enhance the biocidal activity of PPO. Benefiting from these
      satisfactory features, PPO exhibits multiamplified antibacterial efficacy under a
      very low concentration level and white light dose (400-700 nm, 6 mW.cm-2, 5 min,
      1.8 J.cm-2) to Escherichia coli (8 MUM) and Staphylococcus aureus (500 nM).
      Therefore, PPO shows great potential for photodynamic antimicrobial chemotherapy
      at a much lower irradiation light dose and photosensitizer concentration level
      compared to previous reports.

PMID- 30211532
TI  - Morphological and Functional Modifications of Optical Thin Films for Space
      Applications Irradiated with Low-Energy Helium Ions.
AB  - Future space missions will operate in increasingly hostile environments, such as
      those in low-perihelion solar orbits and Jovian magnetosphere. This exploration
      involves the selection of optical materials and components resistant to the
      environmental agents. The conditions in space are reproduced on ground through
      the use of ion accelerators. The effects of He particles coming from the solar
      wind impinging on a gold thin film have been systematically investigated,
      considering absorbed doses compatible with the duration of the European Space
      Agency Solar Orbiter mission. Structural and morphological changes have been
      proved to be dependent not only on the dose but also on the irradiation flux. A
      predictive model of the variation of thin film reflectance has been developed for
      the case of lower flux irradiation. The results are discussed regarding
      reliability and limitations of laboratory testing. The outcomes are important to
      address the procedures for the space qualification tests of optical coatings.

PMID- 30211533
TI  - Thin-Film Nanocomposite Forward-Osmosis Membranes on Hydrophilic Microfiltration
      Support with an Intermediate Layer of Graphene Oxide and Multiwall Carbon
      Nanotube.
AB  - A novel thin-film nanocomposite forward-osmosis (FO) membrane was fabricated on
      hydrophilic nylon microfiltration (MF) support by interfacial polymerization with
      the assistance of an intermediate layer of graphene oxide and multiwall carbon
      nanotube (GO/MWCNT). The chemical composition, structure, and surface properties
      of the synthesized FO membranes were studied using various characterization
      methods. It was found that the GO/MWCNT composite layer not only provided
      ultrafast nanochannels for water transport but also reduced the thickness of the
      polyamide layer by up to 60%. As a result, the novel FO membrane exhibited a
      higher water flux and lower reverse salt flux compared with the membrane
      synthesized without the GO/MWCNT intermediate layer. This method offers promising
      opportunities to fabricate thin-film composite membranes on microfiltration
      substrates for FO application with inhibited concentration polarization
      phenomenon and expected separation performance.

PMID- 30211536
TI  - Making a Bilateral Compression/Tension Sensor by Pre-Stretching Open-Crack
      Networks in Carbon Nanotube Papers.
AB  - Highly stretchable strain sensors are key elements of new applications in
      wearable electronics and soft robotics. Most of the available technologies only
      measure positive strain (stretching), and cannot measure negative strains
      (compression). We propose here a stretchable technology that enables the
      measurement of both negative and positive strains with high sensitivity. A carbon
      nanotube paper is pre-cracked to introduce a well-controlled network of open
      cracks as the sensing element; then, the pre-cracked paper is sandwiched by a
      thermoplastic elastomer. The resulting sensor is also pre-stretched and subjected
      to thermal annealing, which removes any residual stress so that the pre-stretched
      configuration remains stable. This process results in a stretchable structure
      with a network of open cracks that is sensitive to both negative and positive
      strains. We demonstrate that such sensors can measure negative strains up to -13%
      with high sensitivity and robust stretchability.

PMID- 30211534
TI  - Asymmetric Membrane for Digital Detection of Single Bacteria in Milliliters of
      Complex Water Samples.
AB  - In this work, we introduce an asymmetric membrane as a simple and robust
      nanofluidic platform for digital detection of single pathogenic bacteria directly
      in 10 mL of unprocessed environmental water samples. The asymmetric membrane,
      consisting of uniform micropores on one side and a high density of vertically
      aligned nanochannels on the other side, was prepared within 1 min by a facile
      method. The single membrane covers all the processing steps from sample
      concentration, purification, and partition to final digital loop-mediated
      isothermal amplification (LAMP). By simple filtration, bacteria were enriched and
      partitioned inside the micropores, while inhibitors typically found in the
      environmental samples ( i.e., proteins, heavy metals, and organics) were washed
      away through the nanochannels. Meanwhile, large particles, indigenous plankton,
      and positively charged pollutants in the samples were excluded by using a
      sacrificial membrane stacked on top. After initial filtration, modified LAMP
      reagents, including NaF and lysozyme, were loaded onto the membrane. Each pore in
      the asymmetric membrane functioned as an individual nanoreactor for selective,
      rapid, and efficient isothermal amplification of single bacteria, generating a
      bright fluorescence for direct counting. Even though high levels of inhibitors
      were present, absolute quantification of Escherichia coli and Salmonella directly
      in an unprocessed environmental sample (seawater and pond water) was achieved
      within 1 h, with sensitivity down to single cell and a dynamic range of 0.3-10000
      cells/mL. The simple and low-cost analysis platform described herein has an
      enormous potential for the detection of pathogens, exosomes, stem cells, and
      viruses as well as single-cell heterogeneity analysis in environmental, food, and
      clinical research.

PMID- 30211535
TI  - Mesoporous Pd@Ru Core-Shell Nanorods for Hydrogen Evolution Reaction in Alkaline
      Solution.
AB  - The activity and stability of bimetallic nanocatalysts strongly depend on their
      structures, compositions, and interfaces. Here, we report the synthesis of
      mesoporous Pd@Ru core-shell bimetallic nanorods composed of face-centered cubic
      Pd and hexagonal close-packed Ru. The nanorods have two types of cavities with
      diameters of 3.0 +/- 0.9 and 20.3 +/- 8.1 nm. The mutual diffusion process
      between Ru and Pd is characterized by the high-angle annular dark-field scanning
      transmission electron microscopy, energy-dispersive X-ray spectroscopy mapping,
      and the synchrotron radiation photoemission spectroscopy measurements. The
      mesoporous Pd@Ru nanorods exhibit superior catalytic performance and stability
      for hydrogen evolution reactions (overpotentials of 30 mV at 10 mA.cm-2 in 1.0 M
      KOH solution and 37 mV at 10 mA.cm-2 in 0.5 M H2SO4 solution).

PMID- 30211537
TI  - Enriching Mn-Doped ZnSe Quantum Dots onto Mesoporous Silica Nanoparticles for
      Enhanced Fluorescence/Magnetic Resonance Imaging Dual-Modal Bio-Imaging.
AB  - Multimodal imaging is more suitable for disease diagnosis because of its ability
      to provide more complementary and accurate information over single-mode imaging.
      Mn-doped quantum dots (QDs), especially Mn-doped ZnS (ZnSe) QDs, possess unique
      fluorescent and magnetic properties and are thus attractive for
      fluorescence/magnetic resonance imaging (MRI) dual-mode imaging. However, the
      optimal dopant (Mn2+) concentration for maximizing the fluorescence of QDs is
      relatively low for the MRI imaging. Herein, based on the large Stokes shift of Mn
      doped ZnSe QDs, an enrichment strategy with mesoporous silica (MSN) loading was
      explored for constructing a highly luminescent/paramagnetism Mn-doped ZnSe QDs
      assembly (MSN@QDs) for improved MRI/optical dual-model imaging. After assembly,
      the loading density of QDs in MSNs was estimated to be 152 +/- 12. Upon loading,
      the fluorescence of the MSN@QDs assembly was enriched along with QDs (enrichment
      factor of ~143). Because of the large Stokes shift (~200 nm), no appreciable
      concentration quenching was observed. Meanwhile, the T1 MR contrast was also
      increased both in vitro and in vivo through improved local Mn2+ concentration,
      realizing MRI signal enrichment. In fluorescence imaging investigations, MSN@QDs
      showed better performance over both single QDs and equivalent numbers of MSN-free
      single QD. Therefore, this enrichment strategy allowed simultaneous signal
      enhancement of the two imaging modes of Mn-doped ZnSe QDs.

PMID- 30211538
TI  - Improving the Mechanical Rigidity of Hyaluronic Acid by Integration of a
      Supramolecular Peptide Matrix.
AB  - Hyaluronic acid (HA), a major component of the extracellular matrix, is an
      attractive material for various medical applications. Yet, its low mechanical
      rigidity and fast in vivo degradation hinder its utilization. Here, we
      demonstrate the reinforcement of HA by its integration with a low-molecular
      weight peptide hydrogelator to produce a composite hydrogel. The formulation of
      HA with the fluorenylmethoxycarbonyl diphenylalanine (FmocFF) peptide, one of the
      most studied self-assembling hydrogel-forming building blocks, showing notable
      mechanical properties, resulted in the formation of stable, homogeneous
      hydrogels. Electron microscopy analysis demonstrated a uniform distribution of
      the two matrices in the composite forms. The composite hydrogels showed improved
      mechanical properties and stability to enzymatic degradation while maintaining
      their biocompatibility. Moreover, the storage modulus of the FmocFF/HA composite
      hydrogels reached up to 25 kPa. The composite hydrogels allowed sustained release
      of curcumin, a hydrophobic polyphenol showing antioxidant, anti-inflammatory, and
      antitumor activities. Importantly, the rate of curcumin release was modulated as
      a function of the concentration of the FmocFF peptide within the hydrogel matrix.
      This work provides a new approach for conferring mechanical rigidity and
      stability to HA without the need of cross-linking, thus potentially facilitating
      its utilization in different clinical applications, such as sustained drug
      release.

PMID- 30211539
TI  - Self-Reporting Colorimetric Analysis of Drug Release by Molecular Imprinted
      Structural Color Contact Lens.
AB  - As a prospective ophthalmic drug delivery device, contact lenses attract a lot of
      attention because of the improved drug residence time and bioavailability.
      Herein, we proposed and fabricated a molecular imprinted structural color contact
      lens for sustained timolol release which could self-report the release process by
      color change. The specific recognition of target timolol by molecular imprinted
      sites can not only increase the loading amount and the residence time of the drug
      but also endow the structure color of lens remarkable blue shift with the
      accumulative release of timolol. The fascinating contact lens can be further used
      for controlling release of a large number of ophthalmic drugs and has high
      potential to be a new generation of functional contact lenses.

PMID- 30211540
TI  - Allosteric Modulation of JNK Docking Site Interactions with ATP-Competitive
      Inhibitors.
AB  - The c-Jun N-terminal kinases (JNKs) play a wide variety of roles in cellular
      signaling processes, dictating important, and even divergent, cellular fates.
      These essential kinases possess docking surfaces distal to their active sites
      that interact with diverse binding partners, including upstream activators,
      downstream substrates, and protein scaffolds. Prior studies have suggested that
      the interactions of certain protein-binding partners with one such JNK docking
      surface, termed the D-recruitment site (DRS), can allosterically influence the
      conformational state of the ATP-binding pocket of JNKs. To further explore the
      allosteric relationship between the ATP-binding pockets and DRSs of JNKs, we
      investigated how the interactions of the scaffolding protein JIP1, as well as the
      upstream activators MKK4 and MKK7, are allosterically influenced by the ATP
      binding site occupancy of the JNKs. We show that the affinity of the JNKs for
      JIP1 can be divergently modulated with ATP-competitive inhibitors, with a >50
      fold difference in dissociation constant observed between the lowest- and highest
      affinity JNK1-inhibitor complexes. Furthermore, we found that we could promote or
      attenuate phosphorylation of JNK1's activation loop by MKK4 and MKK7, by varying
      the ATP-binding site occupancy. Given that JIP1, MKK4, and MKK7 all interact with
      JNK DRSs, these results demonstrate that there is functional allostery between
      the ATP-binding sites and DRSs of these kinases. Furthermore, our studies suggest
      that ATP-competitive inhibitors can allosterically influence the intracellular
      binding partners of the JNKs.

PMID- 30211541
TI  - How Does Polymerization Regulate Human Acetyl-CoA Carboxylase 1?

PMID- 30211542
TI  - Quantitative Lipoprotein Subclass and Low Molecular Weight Metabolite Analysis in
      Human Serum and Plasma by 1H NMR Spectroscopy in a Multilaboratory Trial.
AB  - We report an extensive 600 MHz NMR trial of quantitative lipoprotein and small
      molecule measurements in human blood serum and plasma. Five centers with eleven
      600 MHz NMR spectrometers were used to analyze 98 samples including 20 quality
      controls (QCs), 37 commercially sourced, paired serum and plasma samples, and two
      National Institute of Science and Technology (NIST) reference material 1951c
      replicates. Samples were analyzed using rigorous protocols for sample preparation
      and experimental acquisition. A commercial lipoprotein subclass analysis was used
      to quantify 105 lipoprotein subclasses and 24 low molecular weight metabolites
      from the NMR spectra. For all spectrometers, the instrument specific variance in
      measuring internal QCs was lower than the percentage described by the National
      Cholesterol Education Program (NCEP) criteria for lipid testing [triglycerides
      <2.7%; cholesterol <2.8%; low-density lipoprotein (LDL) cholesterol <2.8%; high
      density lipoprotein (HDL) cholesterol <2.3%], showing exceptional reproducibility
      for direct quantitation of lipoproteins in both matrixes. The average relative
      standard deviations (RSDs) for the 105 lipoprotein parameters in the 11
      instruments were 4.6% and 3.9% for the two NIST samples, whereas they were 38%
      and 40% for the 37 commercially sourced plasmas and sera, respectively, showing
      negligible analytical compared to biological variation. The coefficient of
      variance (CV) obtained for the quantification of the small molecules across the
      11 spectrometers was below 15% for 20 out of the 24 metabolites analyzed. This
      study provides further evidence of the suitability of NMR for high-throughput
      lipoprotein subcomponent analysis and small-molecule quantitation with the
      exceptional required reproducibility for clinical and other regulatory settings.

PMID- 30211543
TI  - Three-Step Isomerization of the Retinal Chromophore during the Anion Pumping
      Cycle of Halorhodopsin.
AB  - The anion pumping cycle of halorhodopsin from Natronomonas pharaonis ( pHR) is
      initiated when the all- trans/15- anti isomer of retinal is photoisomerized into
      the 13- cis/15- anti configuration. A recent crystallographic study suggested
      that a reaction state with 13- cis/15- syn retinal occurred during the anion
      release process, i.e., after the N state with the 13- cis/15- anti retinal and
      before the O state with all- trans/15- anti retinal. In this study, we
      investigated the retinal isomeric composition in a long-living reaction state at
      various bromide ion concentrations. It was found that the 13- cis isomer (csHR'),
      in which the absorption spectrum was blue-shifted by ~8 nm compared with that of
      the trans isomer (taHR), accumulated significantly when a cold suspension of pHR
      rich claret membranes in 4 M NaBr was illuminated with continuous light. Analysis
      of flash-induced absorption changes suggested that the branching of the trans
      photocycle into the 13- cis isomer (csHR') occurs during the decay of an O-like
      state (O') with 13- cis/15- syn retinal; i.e., O' can decay to either csHR' or O
      with all- trans/15- anti retinal. The efficiency of the branching reaction was
      found to be dependent on the bromide ion concentration. At a very high bromide
      ion concentration, the anion pumping cycle is described by the scheme taHR -(
      hnu) -> K -> L1a <-> L1b <-> N <-> N' <-> O' <-> csHR' <-> taHR. At a low bromide
      ion concentration, on the other hand, O' decays into taHR via O.

PMID- 30211544
TI  - Human eIF5 and eIF1A Compete for Binding to eIF5B.
AB  - Eukaryotic translation initiation is a multistep process requiring a number of
      eukaryotic translation initiation factors (eIFs). Two GTPases play key roles in
      the process. eIF2 brings the initiator Met-tRNAi to the preinitiation complex
      (PIC). Upon start codon selection and GTP hydrolysis promoted by the GTPase
      activating protein (GAP) eIF5, eIF2-GDP is displaced from Met-tRNAi by eIF5B-GTP
      and is released in complex with eIF5. eIF5B promotes ribosomal subunit joining,
      with the help of eIF1A. Upon subunit joining, eIF5B hydrolyzes GTP and is
      released together with eIF1A. We found that human eIF5 interacts with eIF5B and
      may help recruit eIF5B to the PIC. An eIF5B-binding motif was identified at the C
      terminus of eIF5, similar to that found in eIF1A. Indeed, eIF5 competes with
      eIF1A for binding and has an ~100-fold higher affinity for eIF5B. Because eIF5 is
      the GAP of eIF2, the newly discovered interaction offers a possible mechanism for
      coordination between the two steps in translation initiation controlled by
      GTPases: start codon selection and ribosomal subunit joining. Our results
      indicate that in humans, eIF5B displacing eIF2 from Met-tRNAi upon subunit
      joining may be coupled to eIF1A displacing eIF5 from eIF5B, allowing the
      eIF5:eIF2-GDP complex to leave the ribosome.

PMID- 30211545
TI  - Suspect and Nontarget Screening of Per- and Polyfluoroalkyl Substances in
      Wastewater from a Fluorochemical Manufacturing Park.
AB  - Although per- and polyfluoroalkyl substances (PFASs) have always been a key issue
      in the global environmental field, there are still a lot of undiscovered PFASs in
      the environment due to new PFAS alternatives developed by manufacturers.
      Wastewater treatment plants (WWTPs), as one of the sources for PFASs, are an
      important part of the process of releasing new PFASs into the environment. In
      this study, suspect screening and PFAS homologue analysis with quadrupole time-of
      flight tandem mass spectrometry were used to discover PFASs in wastewater from a
      WWTP near Yangtze River. Fifteen classes with 90 PFASs were identified, including
      12 legacy PFASs (2 classes), 41 previously reported PFASs (7 classes), and 37 new
      PFASs (6 classes), and 18 of these PFASs were also detected in the nearby Yangtze
      River. Only 1 PFAS class was removed through the treatment processes (fold change
      < 1/6). Conversely, 4 PFAS classes increased through the treatment processes
      (fold change > 6), which could be the transformation products of PFAS precursors.
      These results implied that most discovered PFASs were not effectively removed in
      the WWTP. Chlorine-substituted perfluoroalkyl carboxylates (Cl-PFCAs) as the main
      component of wastewater were detected only in downstream, meaning that Cl-PFCAs
      in downstream possibly originated from the WWTP.

PMID- 30211546
TI  - Porous Anatase-TiO2(B) Dual-Phase Nanorods Prepared from in Situ Pyrolysis of a
      Single Molecule Precursor Offer High Performance Lithium-Ion Storage.
AB  - To overcome the problems faced by TiO2 materials for lithium-ion batteries usage,
      such as easy nanoparticles agglomeration during cycling and poor cycling
      performance, in this study, TiO2 nanorods with the controlled phase compositions
      are prepared via direct pyrolysis of single molecule precursors in combination
      with a simple washing process. By tuning the external cations in the single
      source precursors, three TiO2 samples in a nanorod shape with the compositions of
      pure anatase, anatase-rutile dual phase, and anatase-TiO2(B) dual phase are
      synthesized successfully. High-resolution transmission electron microscopy, X-ray
      powder diffraction, and Raman measurements confirm the phase structures and
      compositions of the three prepared samples. The electrochemical results manifest
      that all the three nanorod-shaped TiO2 samples show the long-term cycling
      stability as negative materials for LIBs. Among them, the TiO2 sample with the
      combination of the anatase and TiO2-B phase shows the best performance, with the
      specific capacity of ~184, 164, 140, 105, 80, and 60 mAh g-1 at 0.1, 0.3, 0.5,
      1.5, 3.0, and 5.0 A g-1, respectively, and showing no capacity loss and low
      resistance after 1000 cycles at 1.5 A g-1. By the analysis of the cyclic
      voltammetry results recorded from different scan rates, the lithium-ion storage
      mechanism is clarified, which is dominated by the semi-infinite linear diffusion
      (anatase phase) in combination with the partial surface pseudocapacitive
      contribution [TiO2(B) phase]. As a result, this sample shows a great potential as
      a negative material for LIBs because of its electrochemical stability, high
      specific capacity, and superior rate capability. The proof-of-concept design of
      the anatase and TiO2-B dual phase may provide a new strategy for the synthesis of
      high performance TiO2-based anode material for LIBs.

PMID- 30211547
TI  - Supramolecular-Enhanced Charge Transfer within Entangled Polyamide Chains as the
      Origin of the Universal Blue Fluorescence of Polymer Carbon Dots.
AB  - The emission of a bright blue fluorescence is a unique feature common to the vast
      variety of polymer carbon dots (CDs) prepared from carboxylic acid and amine
      precursors. However, the difficulty to assign a precise chemical structure to
      this class of CDs yet hampers the comprehension of their underlying luminescence
      principle. In this work, we show that highly blue fluorescent model types of CDs
      can be prepared from citric acid and ethylenediamine through low temperature
      synthesis routes. Facilitating controlled polycondensation processes, the CDs
      reveal sizes of 1-1.5 nm formed by a compact network of short polyamide chains of
      about 10 monomer units. Density functional theory calculations of these model CDs
      uncover the existence of a spatially separated highest occupied molecular orbital
      and a lowest unoccupied molecular orbital located at the amide and carboxylic
      groups, respectively. Photoinduced charge transfer between these groups thus
      constitutes the origin of the strong blue fluorescence emission. Hydrogen-bond
      mediated supramolecular interactions between the polyamide chains enabling a
      rigid network structure further contribute to the enhancement of the radiative
      process. Moreover, the photoinduced charge transfer processes in the polyamide
      network structure easily explain the performance of CDs in applications as
      revealed in studies on metal ion sensing. These findings thus are of general
      importance to the further development of polymer CDs with tailored properties as
      well as for the design of technological applications.

PMID- 30211548
TI  - XANES-Based Determination of Redox Potentials Imposed by Steel Corrosion Products
      in Cement-Based Media.
AB  - The redox potential (Eh) in a cementitious nuclear waste repository is critical
      to the retardation behavior of redox-sensitive radionuclides (RNs), and largely
      controlled by embedded steel corrosion but hard to be determined experimentally.
      Here, we propose an innovative Eh determination method based on
      chemical/spectroscopic measurements. Oxidized nuclides (UVI, SeIV, MoVI, and SbV)
      were employed as species probes to detect the Eh values imposed by steel (Fe0)
      and steel corrosion products (magnetite/hematite, and magnetite/goethite couples)
      in cement pore water. Nuclides showed good sorption affinity, especially toward
      Fe0, in decreasing Kd order for U > Sb > Se > Mo under both N2 and H2
      atmospheres. The reduced nuclide species were identified as UO2, U4O9, FeSe,
      FeSe2, Se0, Sb0, and Sb2O3, but no redox transformation occurred for Mo. Eh
      values were obtained by using the Nernst equation. Remarkably, their values fell
      in a small range centered around -456 mV at pH ~ 13.5 for both Fe0 and Fe
      oxyhydroxides couples. This Eh value appears to be controlled by the
      nanocrystalline Fe(OH)2/Fe(OH)3 or (Fe1- x,Ca x)(OH)2/Fe(OH)3 couple, whose
      presence was confirmed by pair distribution function analyses. This approach
      could pave the way for describing the Eh gradient in reinforced concrete where
      traditional Eh measurements are not feasible.

PMID- 30211549
TI  - Covalent Radical Pairs as Spin Qubits: Influence of Rapid Electron Motion between
      Two Equivalent Sites on Spin Coherence.
AB  - Ultrafast photodriven electron transfer reactions starting from an excited
      singlet state in an organic donor-acceptor molecule generate a radical pair (RP)
      in which the two spins are initially entangled and, in principle, can serve as
      coupled spin qubits in quantum information science (QIS) applications, provided
      that spin coherence lifetimes in these RPs are long. Here we investigate the
      effects of electron transfer between two equivalent sites comprising the reduced
      acceptor of the RP. A covalent electron donor-acceptor molecule (D-C-A24+)
      including a p-methoxyaniline donor (D), a 4-aminonaphthalene-1,8-imide
      chromophoric primary acceptor (C), and a m-xylene bridged cyclophane having two
      equivalent phenyl-extended viologens (A24+) as a secondary acceptor was
      synthesized along with the analogous molecule having one phenyl-extended viologen
      acceptor and a second, more difficult to reduce 2,5-dimethoxyphenyl-extended
      viologen in a very similar cyclophane structure (D-C-A4+). Photoexcitation of C
      within each molecule results in subnanosecond formation of D+*-C-A23+* and D+*-C
      A3+*. The spin dynamics of these RPs were characterized by time-resolved EPR
      spectroscopy and magnetic field effects on the RP yield in both CH3CN and CD3CN.
      The data show that rapid electron hopping within A23+* promotes spin decoherence
      in D+*-C-A23+* relative to D+*-C-A3+* having a monomeric acceptor, while the
      interaction of the RP electron spins with the nuclear spins of the solvent have
      little or no effect on the spin dynamics. These observations provide important
      information for designing and understanding novel molecular assemblies of spin
      qubits with long coherence times for QIS applications.

PMID- 30211550
TI  - Application of Environmental DNA Metabarcoding for Predicting Anthropogenic
      Pollution in Rivers.
AB  - Rivers are among the most threatened freshwater ecosystems, and anthropogenic
      activities are affecting both river structures and water quality. While assessing
      the organisms can provide a comprehensive measure of a river's ecological status,
      it is limited by the traditional morphotaxonomy-based biomonitoring. Recent
      advances in environmental DNA (eDNA) metabarcoding allow to identify prokaryotes
      and eukaryotes in one sequencing run, and could thus allow unprecedented
      resolution. Whether such eDNA-based data can be used directly to predict the
      pollution status of rivers as a complementation of environmental data remains
      unknown. Here we used eDNA metabarcoding to explore the main stressors of rivers
      along which community structure changes, and to identify the method's potential
      for predicting pollution status based on eDNA data. We showed that a broad range
      of taxa in bacterial, protistan, and metazoan communities could be profiled with
      eDNA. Nutrients were the main driving stressor affecting communities' structure,
      alpha diversity, and the ecological network. We specifically observed that the
      relative abundance of indicative OTUs was significantly correlated with nutrient
      levels. These OTUs data could be used to predict the nutrient status up to 79%
      accuracy on testing data sets. Thus, our study gives a novel approach to
      predicting the pollution status of rivers by eDNA data.

PMID- 30211551
TI  - Cu(OAc)2-Promoted Ortho C(sp2)-H Amidation of 8-Aminoquinoline Benzamide with
      Acyl Azide: Selective Formation of Aroyl or Acetyl Amide Based on Catalyst
      Loading.
AB  - An efficient method for the C(sp2) amidation of 8-aminoquinoline benzamide by
      acyl azide in the presence of copper acetate has been achieved via C-H
      activation. Interestingly, the loading of copper acetate has a strong influence
      on the outcome of the reaction. The use of 1 equiv of copper acetate produces the
      corresponding aroyl amide, whereas the use of 2 equiv led to acetyl amide. A
      series of substituted benzoyl and acetyl amides has been obtained.

PMID- 30211552
TI  - Determination of Long-Range Distances by Fast Magic-Angle-Spinning Radiofrequency
      Driven 19F-19F Dipolar Recoupling NMR.
AB  - Nanometer-range distances are important for restraining the three-dimensional
      structure and oligomeric assembly of proteins and other biological molecules.
      Solid-state NMR determination of protein structures typically utilizes 13C-13C
      and 13C-15N distance restraints, which can only be measured up to ~7 A because of
      the low gyromagnetic ratios of these nuclear spins. To extend the distance reach
      of NMR, one can harvest the power of 19F, whose large gyromagnetic ratio in
      principle allows distances up to 2 nm to be measured. However, 19F possesses
      large chemical shift anisotropies (CSAs) as well as large isotropic chemical
      shift dispersions, which pose challenges to dipolar coupling measurements. Here,
      we demonstrate 19F-19F distance measurements at high magnetic fields under fast
      magic-angle spinning (MAS) using radiofrequency-driven dipolar recoupling (RFDR).
      We show that 19F-19F cross-peaks for distances up to 1 nm can be readily observed
      in two-dimensional 19F-19F correlation spectra using less than 5 ms of RFDR
      mixing. This efficient 19F-19F dipolar recoupling is achieved using practically
      accessible MAS frequencies of 15-55 kHz, moderate 19F radio frequency field
      strengths, and no 1H decoupling. Experiments and simulations show that the
      fastest polarization transfer for aromatic fluorines with the highest distance
      accuracy is achieved using either fast MAS (e.g., 60 kHz) with large pulse duty
      cycles (>50%) or slow MAS with strong 19F pulses. Fast MAS considerably reduces
      relaxation losses during the RFDR pi-pulse train, making finite-pulse RFDR under
      fast-MAS the method of choice. Under intermediate MAS frequencies (25-40 kHz) and
      intermediate pulse duty cycles (15-30%), the 19F CSA tensor orientation has a
      quantifiable effect on the polarization transfer rate; thus, the RFDR buildup
      curves encode both distance and orientation information. At fast MAS, the impact
      of CSA orientation is minimized, allowing pure distance restraints to be
      extracted. We further investigate how relayed transfer and dipolar truncation in
      multifluorine environments affect polarization transfer. This fast-MAS 19F RFDR
      approach is complementary to 19F spin diffusion for distance measurements and
      will be the method of choice under high-field fast-MAS conditions that are
      increasingly important for protein structure determination by solid-state NMR.

PMID- 30211554
TI  - Directed C-H Bond Functionalization: A Unified Approach to Formal Syntheses of
      Amorfrutin A, Cajaninstilbene Acid, Hydrangenol, and Macrophyllol.
AB  - Formal syntheses of natural products amorfrutin A, cajaninstilbene acid,
      hydrangenol, and macrophyllol have been accomplished on the basis of successive C
      H bond functionalization of ready-stock benzoic acids. This concise strategy
      involves transition-metal-catalyzed directed C-H olefination, C-H hydroxylation,
      and acid-mediated C-H prenylation as key steps.

PMID- 30211553
TI  - Reactive Oxygen Species and p53 Mediated Activation of p38 and Caspases is
      Critically Involved in Kaempferol Induced Apoptosis in Colorectal Cancer Cells.
AB  - Here the molecular mechanisms of Kaempferol were examined in colorectal cancers
      (CRCs). Kaempferol significantly exerted antiproliferative and cytotoxic effect
      in HCT116, HCT15, and SW480 cells. Also, Kaempferol increased sub G1 population,
      G2/M arrest, and the numbers of TUNEL cells in HCT116 colorectal cancer cells.
      Also, Kaempferol increased the PARP cleavages and activation of caspase-8, -9,
      and -3, phospho-p38 MAPK, p53, and p21 in HCT116 and HCT15 cells. Of note,
      Kaempferol generated reactive oxygen species (ROS) (43.7 +/- 0.56 vs 25.8 +/-
      0.43, P < 0.01) in HCT116 cells and reversely ROS inhibitor NAC obstructed the
      effects of Kaempferol to cleave PARP and caspase-3 and activate phosphorylation
      of p38 MAPK in HCT116 colorectal cancer cells. Likewise, pancaspase inhibitor z
      vad-fmk, p38 MAPK inhibitor SB203580, and p53 depletion blocked PARP and caspase
      3 in Kaempferol treated HCT116 colorectal cancer cells. Therefore, these findings
      provide novel insight that ROS and p53 signalings mediate p38 phosphorylation and
      caspase activation in Kaempferol stimulated apoptosis in CRCs.

PMID- 30211555
TI  - Rh(III)-Catalyzed C(8)-H Functionalization of Quinolines via Simultaneous C-C and
      C-O Bond Formation: Direct Synthesis of Quinoline Derivatives with Antiplasmodial
      Potential.
AB  - Here, a facile and efficient protocol for the synthesis of 3-hydroxyquinolin-8-yl
      propanoates via Rh(III)-catalyzed C(8)-H activation of 2-substituted quinolines
      has been developed. The reaction proceeds via C(8)-H activation,
      functionalization with acrylates, followed by intramolecular migration of the
      oxygen atom from quinoline N-oxides to the acrylate moiety. In this approach, N
      oxide plays a dual role of a traceless directing group as well as a source of an
      oxygen atom for hydroxylation. This catalytic method involves simultaneous
      formation of new C-C and C-O bonds and is applicable only for C2-substituted
      quinolines. A catalytically competent five-membered rhodacycle has been
      characterized, thus revealing a key intermediate in the catalytic cycle. In
      silico docking studies against Falcipan-2 have revealed that 3a, 3b, 3g, and 3m
      have better scores. In vitro evaluation of selected compounds against CQ
      sensitive pf3D7 and CQ-resistant pfINDO strains provided evidence that 3d (IC50
      13.3 MUM) and 3g (IC50 9.5 MUM) had good promise against Plasmodium falciparum in
      the in vitro culture. Compound 3g was found to be the most potent on the basis of
      both in vitro antiplasmodial activity [IC50 9.5 MUM ( Pf3D7) and 11.9 MUM (
      PfINDO), resistance index 1.25] and in silico studies.

PMID- 30211556
TI  - Effects of Preferential Counterion Interactions on the Specificity of RNA
      Folding.
AB  - The real-time search for native RNA structure is essential for the operation of
      regulatory RNAs. We previously reported that a fraction of the Azoarcus ribozyme
      achieves a compact structure in less than a millisecond. To scrutinize the forces
      that drive initial folding steps, we used time-resolved SAXS to compare the
      folding dynamics of this ribozyme in thermodynamically isostable concentrations
      of different counterions. The results show that the size of the fast-folding
      population increases with the number of available counterions and correlates with
      the flexibility of initial RNA structures. Within 1 ms of folding, Mg2+ exhibits
      a smaller preferential interaction coefficient per charge, DeltaGamma+/ Z, than
      Na+ or [Co(NH3)6]3+. The lower DeltaGamma+/ Z corresponds to a smaller yield of
      folded RNA, although Mg2+ stabilizes native RNA more efficiently than other ions
      at equilibrium. These results suggest that strong Mg2+-RNA interactions impede
      the search for globally native structure during early folding stages.

PMID- 30211557
TI  - Optimization of a Degradable Polymer-Lipid Nanoparticle for Potent Systemic
      Delivery of mRNA to the Lung Endothelium and Immune Cells.
AB  - mRNA therapeutics hold great potential for treating a variety of diseases through
      protein-replacement, immunomodulation, and gene editing. However, much like siRNA
      therapy the majority of progress in mRNA delivery has been confined to the liver.
      Previously, we demonstrated that poly(beta-amino esters), a class of degradable
      polymers, are capable of systemic mRNA delivery to the lungs in mice when
      formulated into nanoparticles with poly(ethylene glycol)-lipid conjugates. Using
      experimental design, a statistical approach to optimization that reduces
      experimental burden, we demonstrate herein that these degradable polymer-lipid
      nanoparticles can be optimized in terms of polymer synthesis and nanoparticle
      formulation to achieve a multiple order-of-magnitude increase in potency.
      Furthermore, using genetically engineered Cre reporter mice, we demonstrate that
      mRNA is functionally delivered to both the lung endothelium and pulmonary immune
      cells, expanding the potential utility of these nanoparticles.

PMID- 30211558
TI  - Cascade Synthesis of Benzothieno[3,2- b]indoles under Oxidative Conditions
      Mediated by CuBr and tert-Butyl Hydroperoxide.
AB  - A series of biologically relevant compounds of benzothieno[3,2- b]indole
      derivatives were conveniently synthesized from reactions of N-protected 2-((2
      bromophenyl)ethynyl)anilines and potassium ethylxanthate, mediated by cuprous
      bromide/ tert-butyl hydroperoxide. The method features the construction of the
      pyrrole and thiophene rings in a cascade sequence with the pyrrole ring being
      formed prior to the thiophene ring via a possible reactive Cu(III)-pyrrole
      intermediate.

PMID- 30211559
TI  - A Rhodium-Catalyzed [3 + 2] Annulation of General Aromatic Aldimines/Ketimines
      and N-Substituted Maleimides.
AB  - A new class of rhodium-catalyzed, C-H activation triggered [3 + 2] annulations of
      aromatic aldimines or ketimines and maleimides was reported in this study. A
      broad scope of general imines without electron-withdrawing groups were
      successfully activated and could effectively react with N-substituted maleimide
      to afford pericyclic, multichiral centered amines in good yields and with
      excellent diastereoselectivity.

PMID- 30211560
TI  - Synthesis and Physical Properties of Polyfluorinated Cycloparaphenylenes.
AB  - Fluorinated [6]- and [9]cycloparaphenylene (CPP) derivatives, 8F-[6]CPP and 12F
      [9]CPP, were synthesized based on the previous synthesis of the parent CPPs.
      While the reductive aromatization conditions used in the final step of the
      synthesis of the parent CPPs did not work for the fluorinated compounds, the use
      of PBr3 and SnCl2 in acetonitrile successfully accomplished the desired
      transformation. The structures of F-CPPs were determined by single-crystal X-ray
      analysis. Photo- and electrochemical analyses and host-guest chemistry revealed
      the effects of the introduction of fluorine atoms.

PMID- 30211561
TI  - Predicting Nanotube Fibrogenicity through Stem Cell-Mediated Fibroblast Focus and
      Spheroid Formation.
AB  - Fibroblast stem cells or stemlike cells (FSCs) are proposed to play a pivotal
      role in extracellular matrix (ECM) regeneration by serving as a key source of ECM
      producing fibroblasts. We developed a mechanism-based in vitro model for
      fibrogenicity testing of nanomaterials based on their ability to induce FSCs.
      Using a FSC-enriched fibroblast focus model to mimic in vivo fibrogenic response,
      we demonstrated a dose-dependent increase in fibroblast focus formation and
      collagen production by primary lung fibroblasts treated with multiwalled carbon
      nanotubes (MWCNTs). The focus-forming cells exhibited stem properties as
      indicated by stem cell markers expression, sphere formation, and ALDH activity
      assays. Inhibition of ALDH activity diminished the focus and sphere formation as
      well as collagen production. In vivo animal studies supported the in vitro
      findings and indicated the potential utility of FSC-based assays as a rapid
      screening tool for fibrogenicity testing of nanomaterials. This study also
      unveils a novel mechanism of nanotube-induced fibrogenesis through ALDH-dependent
      FSC activation.

PMID- 30211562
TI  - Carbene-Catalyzed [4 + 2] Cycloadditions of Vinyl Enolate and (in Situ Generated)
      Imines for Enantioselective Synthesis of Quaternary alpha-Amino Phosphonates.
AB  - A carbene-catalyzed enantioselective addition of enals to five-membered cyclic
      imines is developed. The reaction gives chiral quaternary alpha-amino
      phosphonates bearing tetrasubstituted carbon centers with excellent
      enantioselectivities. The imine substrates can be generated in situ from the
      corresponding amines under an oxidative condition that is compatible with the
      carbene catalysis. Thus, a one-pot cross-dehydrogenative-coupling (CDC) reaction
      between enals and amines is also realized with high enantioselectivity remaining.
      The method provides quick enantioselective access to amino phosphonates with
      potential applications in medicines and pesticides.

PMID- 30211563
TI  - Complexation of Fullerenes by Subphthalocyanine Dimers.
AB  - Tweezer-like molecules comprised of two boron subphthalocyanine (SubPc) units
      were prepared by Sonogashira couplings and investigated using NMR spectroscopy
      for their ability to bind fullerenes (C60 and C70). The preorganization of the
      tweezers provided association constants of ca. 103 M-1 in toluene- d8, while a
      SubPc monomer did not show any association. Nevertheless, the SubPc monomer
      crystallized with the fullerenes as 2:1 complexes, supporting the favorable
      tweezer-like design for complexation, which was further corroborated by
      computations.

PMID- 30211564
TI  - Highly Selective Palladium-Catalyzed Arene C-H Acyloxylation with
      Benzothiadiazole as a Modifiable Directing Group.
AB  - An efficient protocol for the palladium-catalyzed direct arene C-H acyloxylation
      of benzothiadiazole-arene derivatives is reported for the first time. The key
      strategy is the employment of benzothiadiazole as a modifiable directing group.
      The highly selective mono- or bis-acyloxylation can be achieved by tuning the
      reaction conditions, affording various acyloxylated benzothiadiazole derivatives,
      which could offer a rational tailoring of their electronic properties and be
      applied in organic electronic and optoelectronic materials. Finally, by diversity
      oriented modification of the benzothiadiazole directing group, the acyloxylated
      products can be readily converted into various valuable functionalized
      (hetero)biaryls.

PMID- 30211566
TI  - Work and well-being in TGNC adults: The moderating effect of workplace
      protections.
AB  - The present study used a psychology of working theory (PWT) framework to test the
      direct and indirect relations of perceived social status and transgender and
      gender nonconforming (TGNC) marginalization (i.e., victimization, nonaffirmation
      of gender identity, negative expectations for the future) with work volition,
      overqualification, and vocational and emotional well-being outcomes (i.e., job
      satisfaction, meaningful work, satisfaction with life, depression) in a sample of
      175 TGNC working adults. This study also tested the moderating effect of one form
      of structural marginalization (lack of legal protections from employment
      discrimination) on the overall pattern of results. Participants were recruited
      using online social media and discussion forums and completed the study survey
      online. For the full sample, perceived social status and nonaffirmation of gender
      identity were associated with vocational and emotional well-being outcomes
      through the mediating role of work volition, and for some paths,
      overqualification. Significant differences emerged in the overall pattern of
      results for those without protections, suggesting that protections from
      discrimination buffer the adverse links of some forms of TGNC marginalization
      with work volition and vocational outcomes. Implications of study findings for
      research, counseling, and advocacy are provided. (PsycINFO Database Record

PMID- 30211567
TI  - Reduced language processing automaticity induces weaker emotions in bilinguals
      regardless of learning context.
AB  - While the evidence for impoverished emotional reactions of bilinguals in their
      weaker second language (L2) accumulates, the underlying mechanisms of this effect
      remain poorly understood. Here, we investigate how unbalanced bilinguals'
      language-specific emotions vary depending on differences in language processing
      automaticity versus in language learning and use contexts. We analyzed behavioral
      emotional reactions in a hypothetical decision-making task with low emotional
      appeal, the Asian disease problem (Study 1) and pupil and valence responses to
      authentic narrative video advertising with high emotional appeal (Study 2). Both
      studies replicated the L2 emotion disadvantage. In decision-making, L2 reactions
      paralleled first language reactions under perceptual load. During the L2
      narrative, the pupil dilated less because of reduced lexical access automaticity
      rather than in response to language-context factors. The findings suggest that
      bilinguals have language-independent emotional representations. Yet, they process
      emotional information conveyed in L2 less automatically, which triggers weaker
      emotional reactions. (PsycINFO Database Record

PMID- 30211565
TI  - Supramolecular Nanostructure Activates TrkB Receptor Signaling of Neuronal Cells
      by Mimicking Brain-Derived Neurotrophic Factor.
AB  - Brain-derived neurotrophic factor (BDNF), a neurotrophin that binds specifically
      to the tyrosine kinase B (TrkB) receptor, has been shown to promote neuronal
      differentiation, maturation, and synaptic plasticity in the central nervous
      system (CNS) during development or after injury and onset of disease.
      Unfortunately, native BDNF protein-based therapies have had little clinical
      success due to their suboptimal pharmacological properties. In the past 20 years,
      BDNF mimetic peptides have been designed with the purpose of activating certain
      cell pathways that mimic the functional activity of native BDNF, but the
      interaction of mimetic peptides with cells can be limited due to the
      conformational specificity required for receptor activation. We report here on
      the incorporation of a BDNF mimetic sequence into a supramolecular peptide
      amphiphile filamentous nanostructure capable of activating the BDNF receptor TrkB
      and downstream signaling in primary cortical neurons in vitro. Interestingly, we
      found that this BDNF mimetic peptide is only active when displayed on a peptide
      amphiphile supramolecular nanostructure. We confirmed that increased neuronal
      maturation is linked to TrkB signaling pathways by analyzing the phosphorylation
      of downstream signaling effectors and tracking electrical activity over time.
      Furthermore, three-dimensional gels containing the BDNF peptide amphiphile (PA)
      nanostructures encourage cell infiltration while increasing functional
      maturation. Our findings suggest that the BDNF mimetic PA nanostructure creates a
      highly bioactive matrix that could serve as a biomaterial therapy in injured
      regions of the CNS. This new strategy has the potential to induce endogenous cell
      infiltration and promote functional neuronal maturation through the presentation
      of the BDNF mimetic signal.

PMID- 30211569
TI  - It's mine! Psychological ownership of one's job explains positive and negative
      workplace outcomes of job engagement.
AB  - Job engagement denotes the extent to which an employee invests the full self in
      performing the job. Extant research has investigated the positive outcomes of job
      engagement, paying little attention to its potential costs to the organizations.
      Integrating the extended self theory and the literature on psychological
      ownership as our overarching theoretical framework, we develop and test the
      double-edged effects of job engagement on workplace outcomes through the
      mediating role of job-based psychological ownership. Analyses of two survey
      studies with multisource multiphase data support that job engagement can lead to
      positive workplace outcomes including in-role performance and organizational
      citizenship behaviors (OCBs) through job-based psychological ownership. At the
      same time, job engagement is also positively related to negative workplace
      outcomes including territorial behavior, knowledge hiding, and pro-job unethical
      behavior through the same mechanism of job-based psychological ownership. These
      indirect effects of job engagement on negative work outcomes are amplified by
      employees' avoidance motivation. The theoretical and practical implications are
      discussed. (PsycINFO Database Record

PMID- 30211568
TI  - Does early executive function predict teacher-child relationships from
      kindergarten to second grade?
AB  - Teacher-child relationships have been linked to children's classroom engagement
      and to academic achievement. However, researchers have paid minimal attention to
      individual child factors that predict the development of these relationships. In
      the current study, we examined executive function (EF) prior to school entry as a
      predictor of teacher-child relationships at kindergarten through second grade. We
      also examined externalizing behavior problems, verbal intelligence, and academic
      achievement as mediators of these associations. Data were from the Family Life
      Project, a prospective, longitudinal sample of N = 1,292 families from
      predominantly low-socioeconomic status (SES) and rural communities in
      Pennsylvania and North Carolina. Children were administered a multidimensional
      battery of EF when they were 48 months old and standardized measures of verbal
      intelligence and academic achievement at prekindergarten. Parents reported on
      externalizing behavior problems when children were 60 months old. Kindergarten,
      first-, and second-grade teachers reported on teacher-child relationships. Growth
      curve models revealed that EF at 48 months positively predicted closeness and
      negatively predicted conflict with teachers in kindergarten but not change in
      closeness or conflict over time. Verbal intelligence mediated the associations
      between EF and both closeness and conflict. EF continued to significantly predict
      conflict, but not closeness, with kindergarten teachers when the mediator was
      included in the model. The results of this study are discussed in the context of
      the implications of children's self-regulation for classroom engagement in a low
      SES sample. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 30211570
TI  - Unaffected siblings of adolescents and adults with fragile X syndrome: Effects on
      maternal well-being.
AB  - The present study investigated the effects of children without disabilities on
      maternal physical and mental health in families with adolescents or adults with
      fragile X syndrome. Mothers with the FMR1 premutation (N = 87) reported on
      behavior problems and functional limitations of their adolescent or adult child
      with fragile X syndrome and their own physical and mental health. Mothers also
      provided a blood sample to determine FMR1 CGG repeat length. The proportion of
      unaffected children in the family significantly buffered the effect of both child
      behavior problems and functional limitations on maternal self-rated health, such
      that having a higher proportion of unaffected children in the family had a
      protective effect on maternal health when the target child had more severe
      behavior problems and functional limitations. There was a similar buffering
      process for maternal depressive symptoms but at a trend level. Additionally,
      maternal CGG repeat length had a significant curvilinear association with self
      rated health, indicating that mothers with midrange repeat lengths reported the
      poorest health, whereas mothers with lower and higher repeat lengths in the
      premutation range reported better health. The data suggest that unaffected
      children in the family may be an important resource for premutation carrier
      mothers. Findings are consistent with previous research indicating that mothers
      with varying levels of genetic liability have variable risk for health problems.
      (PsycINFO Database Record

PMID- 30211572
TI  - Longitudinal associations among maternal depressive symptoms, child emotional
      caretaking, and anxious/depressed symptoms in pediatric cancer.
AB  - Research has shown that children experience increased emotional distress when
      engaging in emotional caretaking of a parent. The current study is the first to
      examine this process in families in which the source of the stress is the child's
      illness. Prospective associations were tested among mothers' depressive symptoms
      near the time of their child's cancer diagnosis, mothers' expressed distress and
      their child's emotional caretaking during an interaction task, and child
      anxious/depressed symptoms at 1 year postdiagnosis. Families (N = 78) were
      recruited from two pediatric hospitals soon after their child's (Ages 5-18) new
      diagnosis or relapse of cancer. Mothers reported on their own depressive symptoms
      and their child's anxious/depressed symptoms near the time of diagnosis or
      recurrence (Time 1) and 1 year later (Time 3). At Time 2 (4 months after Time 1),
      mother-child dyads completed a video-recorded discussion of their experience with
      cancer that was coded for observed maternal expressed distress (anxiety, sadness)
      and observed child emotional caretaking. Maternal expressed distress during the
      interaction was significantly related to more emotional caretaking behaviors by
      both boys and girls. Results of a moderated mediation model showed that child
      emotional caretaking at Time 2 significantly mediated the relation between
      maternal depressive symptoms at Time 1 and child anxious/depressed symptoms at
      Time 3 for girls but not for boys. The findings suggest that children's emotional
      caretaking behaviors contribute to subsequent anxious/depressed symptoms for
      girls, but not for boys, with cancer. (PsycINFO Database Record

PMID- 30211573
TI  - Efficiency of mitochondrial functioning as the fundamental biological mechanism
      of general intelligence (g).
AB  - General intelligence or g is one of the most thoroughly studied concepts in the
      behavioral sciences. Measures of intelligence are predictive of a wide range of
      educational, occupational, and life outcomes, including creative productivity and
      are systematically related to physical health and successful aging. The nexus of
      relations suggests 1 or several fundamental biological mechanisms underlie g,
      health, and aging, among other outcomes. Cell-damaging oxidative stress has been
      proposed as 1 of many potential mechanisms, but the proposal is underdeveloped
      and does not capture other important mitochondrial functions. I flesh out this
      proposal and argue that the overall efficiency of mitochondrial functioning is a
      core component of g; the most fundamental biological mechanism common to all
      brain and cognitive processes and that contributes to the relations among
      intelligence, health, and aging. The proposal integrates research on intelligence
      with models of the centrality of mitochondria to brain development and
      functioning, neurological diseases, and health more generally. Moreover, the
      combination of the maternal inheritance of mitochondrial DNA (mtDNA), the
      evolution of compensatory nuclear DNA, and the inability of evolutionary
      processes to purge deleterious mtDNA in males may contribute to the sex
      difference in variability in intelligence and in other cognitive domains. The
      proposal unifies many now disparate literatures and generates testable
      predictions for future studies. (PsycINFO Database Record (c) 2018 APA, all
      rights reserved).

PMID- 30211574
TI  - Military operational psychology.
AB  - With increasing requirements for expeditionary support to military units, models
      of integrated and embedded psychology have emerged. Operational psychology
      represents one such model. Military operational psychologists receive specialized
      training, are embedded in operational units, and are employed to provide
      operational mission support to organizations and their personnel as opposed to
      providing individual health care per se. The following article describes the
      employment of military operational psychology and discusses its unique
      organizational and ethical challenges. (PsycINFO Database Record

PMID- 30211571
TI  - Does support need to be seen? Daily invisible support promotes next day
      relationship well-being.
AB  - Direct and overt visible support promotes recipients' relationship satisfaction
      but can also exacerbate negative mood. In contrast, subtle and indirect invisible
      support can bypass costs to mood, but it is unclear whether it undermines or
      boosts relationship satisfaction. Because invisible support is not perceived by
      recipients, its relational impact may be delayed across time. Thus, the current
      research used three dyadic daily diary studies (total N = 322 married couples) to
      explore, for the first time, both the immediate (same day) and lagged (next day)
      effects of visible and invisible support on recipients' mood and relationship
      satisfaction. Consistent with prior research, visible support was associated with
      recipients reporting greater relationship satisfaction and greater anxiety the
      same day. In contrast, but also consistent with prior research, invisible support
      had no significant same-day effects, and thus avoided mood costs. Nevertheless,
      invisible support was associated with recipients reporting greater relationship
      satisfaction the next day. Study 3 provided evidence that such effects emerged
      because invisible support was also associated with greater satisfaction with
      partners' helpful behaviors (e.g., household chores) and relationship
      interactions (e.g., time spent together) on the next day. These studies
      demonstrate the importance of assessing different temporal effects associated
      with support acts (which may otherwise go undetected) and provide the first
      evidence that invisible support enhances relationship satisfaction but does so
      across days. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 30211575
TI  - Carving sexuality at its joints: Defining sexual orientation in research and
      clinical practice.
AB  - In this article, we review basic research on sexual orientation for a clinical
      scientist-practitioner audience. We present contemporary and evolving approaches
      to defining and measuring sexual orientation, and we provide suggestions for how
      to translate psychological theory into best practices (i.e., how to select
      appropriate sexuality measures in both research and clinical settings). Our focus
      is on evaluating currently available measures of sexual orientation in terms of
      comprehensiveness and feasibility: How thoroughly are components of sexuality
      captured and how feasible it is to use such measures in research and clinical
      settings? Basic research in sexuality has progressed beyond our current clinical
      practices and should be used as a guide to more responsibly conceptualize
      participants and clients. While we determine that the current options are far
      from perfect, the critical clinician will find that contemporary measures of
      sexual orientation prove more useful than more simplistic predecessors. This
      review will elucidate best strategies for translating sexual orientation research
      and theory into clinical practice and provide clinicians and researchers alike
      with theoretically grounded support for tools of measurement and assessment.
      (PsycINFO Database Record

PMID- 30211577
TI  - Poor response inhibition and peer victimization: A neurocognitive ecophenotype of
      risk for adolescent interpersonal aggression.
AB  - Relationship between poor inhibitory control and adolescent interpersonal
      difficulties is well-documented. However, the way in which an emotionally neutral
      cognitive process (i.e., response inhibition) can lead to interpersonal
      difficulties is less clear. The current study is based on multimodal longitudinal
      data from 3,826 adolescents followed over a 4-year period. The main aim of this
      study was to examine an ecophenotype conceptualization of the association between
      response inhibition and bullying perpetration through increasing vulnerability of
      peer victimization and a negative attributional style toward self and others. To
      test for potential mediations, we first tested the independent effects of the
      main predictor (response inhibition) and proposed mediators (victimization,
      hostile automatic thoughts, and self esteem). Multilevel models highlighted
      independent effects of response inhibition, hostility-related automatic thoughts,
      and self-esteem in susceptibility to peer victimization and bullying
      perpetration, both in terms of general liability and fluctuations at each time
      point over the 4-year period (i.e., between and within person effects). Moreover,
      results from multivariate multilevel path model were in line with the
      ecophenotype conceptualization. Indirect effects indicated that general liability
      of peer victimization mediated the effect of poor response inhibition on bullying
      perpetration. Likewise, general liability and concurrent fluctuations in
      hostility-related automatic thoughts and self-esteem mediated the effect of peer
      victimization on bullying perpetration. The current study highlights the need for
      a comprehensive understanding of bullying perpetration which is only possible
      through consideration of individual characteristics along with environmental
      factors. This framework has the potential to inform targeted intervention
      strategies aimed at reducing peer-to-peer violence. (PsycINFO Database Record (c)
      2018 APA, all rights reserved).

PMID- 30211578
TI  - What you see depends on what you hear: Temporal averaging and crossmodal
      integration.
AB  - In our multisensory world, we often rely more on auditory information than on
      visual input for temporal processing. One typical demonstration of this is that
      the rate of auditory flutter assimilates the rate of concurrent visual flicker.
      To date, however, this auditory dominance effect has largely been studied using
      regular auditory rhythms. It thus remains unclear whether irregular rhythms would
      have a similar impact on visual temporal processing, what information is
      extracted from the auditory sequence that comes to influence visual timing, and
      how the auditory and visual temporal rates are integrated together in
      quantitative terms. We investigated these questions by assessing, and modeling,
      the influence of a task-irrelevant auditory sequence on the type of "Ternus
      apparent motion": group motion versus element motion. The type of motion seen
      critically depends on the time interval between the two Ternus display frames. We
      found that an irrelevant auditory sequence preceding the Ternus display modulates
      the visual interval, making observers perceive either more group motion or more
      element motion. This biasing effect manifests whether the auditory sequence is
      regular or irregular, and it is based on a summary statistic extracted from the
      sequential intervals: their geometric mean. However, the audiovisual interaction
      depends on the discrepancy between the mean auditory and visual intervals: if it
      becomes too large, no interaction occurs-which can be quantitatively described by
      a partial Bayesian integration model. Overall, our findings reveal a cross-modal
      perceptual averaging principle that may underlie complex audiovisual interactions
      in many everyday dynamic situations. (PsycINFO Database Record (c) 2018 APA, all
      rights reserved).

PMID- 30211579
TI  - From simple to complex actions: Response-response bindings as a new approach to
      action sequences.
AB  - Binding between stimulus features and between stimuli and responses has been
      discussed as a central mechanism in human action control: Carrying out a response
      to a stimulus leads to bindings between stimulus and response features, so that
      repetition of one can retrieve the other later on. We find it intriguing that all
      discussions to date focus either on stimulus-stimulus or on stimulus-response
      bindings. Here we argue that response-response bindings are equally relevant for
      action control, if binding really plays a role in action representation. Hence,
      the present study investigates whether the same kind of integration and retrieval
      as observed between stimuli and responses is also possible between two individual
      responses pursuing different goals. A new design including sequential responses
      to a Task A and a Task B, was developed to analyze bindings between separately
      planned and executed responses. In two experiments, the results indicated
      retrieval of the response to Task B as a result of the repetition of the response
      to Task A. This is the first evidence for an integration of two separately
      planned responses in the same event representation. The result has implications
      for the structure of human action representation, indicating binding of
      individual actions in higher order representations, and suggests that binding is
      an even more ubiquitous mechanism in action control than previously shown.
      (PsycINFO Database Record

PMID- 30211580
TI  - Collaborative remembering of emotional autobiographical memories: Implications
      for emotion regulation and collective memory.
AB  - People frequently engage in conversation about shared autobiographical events
      from their lives, particularly those with emotional significance. The
      pervasiveness of this practice raises the question whether shared memory
      reconstruction has the power to influence the memory and emotions associated with
      such events. We developed a novel paradigm that combined the strengths of the
      methods from autobiographical and collaborative memory research traditions to
      examine such consequences. We selected a shared, real-life autobiographical event
      of an exam, and asked students to recall their memory of taking a recent exam
      where they provided a group and/or personal narrative of this autobiographical
      event. Students first recalled the event either collaboratively (C) or
      individually (I), followed by a final individual (I) recall by all. Valence
      ratings as well as the emotional tone of the narratives converged to show that
      prior collaborative remembering down-regulated negative emotion and enhanced the
      positive emotional tone of the memories. The recalled detail in the narratives
      indicated that at initial recall members of collaborative groups reported fewer
      internal details than those who recalled alone, and reported more external
      details in a later recall when working alone. Earlier collaboration also
      increased collective memory such that more of these details were shared among
      prior group members in their later individual recall compared with those who did
      not collaborate before. We discuss the influence of collaborative remembering on
      shaping memory and emotion for autobiographical events as well as the potential
      mechanisms that promote collective autobiographical memory. (PsycINFO Database
      Record

PMID- 30211576
TI  - WHO World Mental Health Surveys International College Student Project: Prevalence
      and distribution of mental disorders.
AB  - Increasingly, colleges across the world are contending with rising rates of
      mental disorders, and in many cases, the demand for services on campus far
      exceeds the available resources. The present study reports initial results from
      the first stage of the WHO World Mental Health International College Student
      project, in which a series of surveys in 19 colleges across 8 countries
      (Australia, Belgium, Germany, Mexico, Northern Ireland, South Africa, Spain,
      United States) were carried out with the aim of estimating prevalence and basic
      sociodemographic correlates of common mental disorders among first-year college
      students. Web-based self-report questionnaires administered to incoming first
      year students (45.5% pooled response rate) screened for six common lifetime and
      12-month DSM-IV mental disorders: major depression, mania/hypomania, generalized
      anxiety disorder, panic disorder, alcohol use disorder, and substance use
      disorder. We focus on the 13,984 respondents who were full-time students: 35% of
      whom screened positive for at least one of the common lifetime disorders assessed
      and 31% screened positive for at least one 12-month disorder. Syndromes typically
      had onsets in early to middle adolescence and persisted into the year of the
      survey. Although relatively modest, the strongest correlates of screening
      positive were older age, female sex, unmarried-deceased parents, no religious
      affiliation, nonheterosexual identification and behavior, low secondary school
      ranking, and extrinsic motivation for college enrollment. The weakness of these
      associations means that the syndromes considered are widely distributed with
      respect to these variables in the student population. Although the extent to
      which cost-effective treatment would reduce these risks is unclear, the high
      level of need for mental health services implied by these results represents a
      major challenge to institutions of higher education and governments. (PsycINFO
      Database Record (c) 2018 APA, all rights reserved).

PMID- 30211582
TI  - "Technology-mediated addictive behaviors constitute a spectrum of related yet
      distinct conditions: A network perspective": Correction to Baggio et al. (2018).
AB  - Reports an error in "Technology-mediated addictive behaviors constitute a
      spectrum of related yet distinct conditions: A network perspective" by Stephanie
      Baggio, Vladan Starcevic, Joseph Studer, Olivier Simon, Sally M. Gainsbury,
      Gerhard Gmel and Joel Billieux (Psychology of Addictive Behaviors, 2018[Aug], Vol
      32[5], 564-572). In the article, an incorrect Online First date appears in the
      article. The correct Online First publication date is July 19, 2018. The online
      version of this article has been corrected. (The following abstract of the
      original article appeared in record 2018-34815-001.) An important ongoing debate
      in the addiction field is whether certain technology-mediated behaviors
      constitute tenable and independent constructs. This study investigated whether
      problematic technology-mediated behaviors could be conceptualized as a spectrum
      of related, yet distinct disorders (spectrum hypothesis), using the network
      approach, which considers disorders as networks of symptoms. We used data from
      the Cohort Study on Substance Use and Risk Factors (C-SURF; Swiss National
      Science Foundation), with a representative sample of young Swiss men (subsample
      of participants engaged in technology-mediated behaviors, n = 3,404). Four
      technology-mediated addictive behaviors were investigated using symptoms derived
      from the Diagnostic and Statistical Manual of Mental Disorders (5th ed.) and the
      component model of addiction: Internet, smartphone, gaming, and cybersex. Network
      analyses included network estimation and visualization, community detection
      tests, and centrality indices. The network analysis identified four distinct
      clusters corresponding to each condition, but only Internet addiction had
      numerous relationships with the other behaviors. This finding, along with the
      finding that there were few relationships between the other behaviors, suggests
      that smartphone addiction, gaming addiction, and cybersex addiction are
      relatively independent constructs. Internet Addiction was often connected with
      other conditions through the same symptoms, suggesting that it could be
      conceptualized as an "umbrella construct," that is, a common vector that mediates
      specific online behaviors. The network analysis thus provides a preliminary
      support to the spectrum hypothesis and the focus on the specific activities
      performed online, while showing that the construct of Internet addiction is
      inadequate. (PsycINFO Database Record

PMID- 30211581
TI  - Affect, craving, and cognition: An EMA study of ad libitum adolescent smoking.
AB  - Reducing smoking among adolescents is a public health priority. Affect, craving,
      and cognitive processes have been identified as predictors of smoking in
      adolescents. The current study examined associations between implicit attitude
      for smoking (assessed via the positive-negative valence implicit association
      test) and affect, craving, and smoking assessed using ecological momentary
      assessment (EMA). Adolescent smokers (n = 154; Mage = 16.57, SD = 1.12) completed
      a laboratory assessment of implicit smoking attitudes and carried a palm-top
      computer for several days while smoking ad libitum. During EMA, they recorded
      affect, craving, and smoking behavior. Data were analyzed using a multilevel path
      analysis. At the between-subjects level, more positive implicit smoking attitude
      was indirectly associated with smoking rate via craving. This association was
      moderated by positive affect, such that it was stronger for those with greater
      traitlike positive affect. At the event (within-subject) level, implicit attitude
      potentiated associations between stress and craving and between positive affect
      and craving. Individuals with a more positive implicit attitude exhibited more
      robust indirect associations between momentary stress-positive affect and
      smoking. In sum, a more positive implicit attitude to smoking was associated with
      overall levels of craving and smoking and might have potentiated momentary affect
      craving associations. Interventions that modify implicit attitude may be an
      approach for reducing adolescent smoking. (PsycINFO Database Record

PMID- 30211583
TI  - Examining the pathways between bully victimization, depression, academic
      achievement, and problematic drinking in adolescence.
AB  - In this article, we expand and test several theoretical models addressing the
      longitudinal relationships between bully victimization, depression, academic
      achievement, and problematic drinking from 3 approaches: Interpersonal risk
      model, symptom driven model, and a transactional model. Unfortunately, prior
      research has failed to consider these associations at the within-person level,
      which is arguably a more relevant level of analysis. Participants were 1,875
      students sampled from four Midwestern middle schools and followed for 2 years.
      Baseline age ranged from 11-13 years with a racially diverse sample (44.3%
      African American, 29.2% White, 7% Hispanic, 3% Asian/Pacific Islander, and 16.5%
      Multi-Racial). The current study used an auto-regressive latent trajectory with
      structured residuals (ALT-SR) model to examine the within-person cross-lagged
      associations between bully victimization, depression, academic achievement, and
      problematic drinking. Results indicated support for an interpersonal risk model,
      where experiences of early bullying victimization resulted in a cascade of
      problems throughout middle school. Within this interpersonal risk model we also
      established that academic achievement was a key mechanism linking bully
      victimization to problematic drinking during adolescence We did not find evidence
      for a traditional symptom driven model (e.g., stemming from depression); however,
      we did find long-term problems stemming from early problematic drinking. Results
      are discussed in relation to prevention interventions for problematic drinking as
      well as screenings for early adolescent depression, bully victimization, and
      academic problems. (PsycINFO Database Record

PMID- 30211584
TI  - "Sexual identity of drinking companions, drinking motives, and drinking behaviors
      among young sexual minority women: An analysis of daily data": Correction to
      Dworkin et al. (2018).
AB  - Reports an error in "Sexual identity of drinking companions, drinking motives,
      and drinking behaviors among young sexual minority women: An analysis of daily
      data" by Emily R. Dworkin, Jennifer Cadigan, Tonda Hughes, Christine Lee and
      Debra Kaysen (Psychology of Addictive Behaviors, 2018[Aug], Vol 32[5], 540-551).
      In the article an incorrect Online First date appears in the article. This
      article did not post Online First. The online version of this article has been
      corrected. (The following abstract of the original article appeared in record
      2018-36320-001.) Research has indicated that sexual minority women (SMW) drink
      more than do their heterosexual counterparts. Minority stress theory postulates
      that this increased drinking is motivated by efforts to modulate distress related
      to minority status, highlighting the potential importance of coping and
      enhancement drinking motives. Social learning theory postulates that SMW are
      motivated to drink more because their social companions model drinking behavior
      and convey social norms regarding appropriate alcohol consumption, suggesting
      that socialization and conformity motives may be important. The degree to which
      different motives for drinking affect SMW's alcohol consumption may depend in
      part on whether SMW drink with other sexual minorities, but this has not been
      investigated. This study examined daily data across 2 separate 14-day bursts to
      understand associations among daily drinking motives, the sexual identity of
      drinking companions, and alcohol consumption among 67 young SMW who reported on
      553 social drinking days. On days when SMW had higher than typical socialization
      and enhancement motives, they tended to drink more, and SMW who typically had
      higher coping motives tended to drink more on any given day. Further, higher than
      typical enhancement motives were associated with heavier drinking on days when
      SMW drank with only heterosexual companions, relative to days when they drank
      with only sexual minority companions or in mixed sexual-identity groups. SMW's
      typical conformity motives were more strongly related to drinking on days when
      SMW drank in mixed sexual-identity groups relative to heterosexual companions
      only. These results indicate that SMW's drinking motives and drinking companions
      may be important targets for future research and intervention. (PsycINFO Database
      Record

PMID- 30211585
TI  - "A cluster-analytic approach to determining drinking motives and personality
      typologies: Trauma group differences and respective relations to PTSD and
      problematic alcohol use": Correction to Hawn et al. (2018).
AB  - Reports an error in "A cluster-analytic approach to determining drinking motives
      and personality typologies: Trauma group differences and respective relations to
      PTSD and problematic alcohol use" by Sage E. Hawn, Erin D. Kurtz, Emily Brown,
      Ruth C. Brown, Erin C. Berenz, Scott McDonald, Treven Pickett, Carla Kmett
      Danielson and Ananda Amstadter (Psychology of Addictive Behaviors, 2018[Aug], Vol
      32[5], 528-539). In the article an incorrect Online First date appears in the
      article. The correct Online First publication date is July 19, 2018. The online
      version of this article has been corrected. (The following abstract of the
      original article appeared in record 2018-34812-001.) Veterans with posttraumatic
      stress disorder (PTSD) are at elevated risk for alcohol use problems, a
      relationship commonly explained by using alcohol to cope with unpleasant symptoms
      of PTSD. However, patterns of alcohol use motives, more broadly, have not been
      well characterized in veteran samples, nor have they been evaluated in the
      context of other relevant factors, such as normative personality traits. The aims
      of the present study were to identify empirically derived drinking motive and
      personality typologies to determine whether these typologies differ as a function
      of PTSD status (i.e., nontrauma control, trauma exposed-no PTSD, and PTSD) and to
      evaluate associations between typology and PTSD symptom severity and alcohol
      consumption, respectively. Cluster analyses identified a 4-cluster solution.
      Results indicated that these typologies differed significantly according to
      trauma group as well as across levels of PTSD symptom severity and alcohol use.
      Specifically, Cluster 4 represented individuals at highest risk for both PTSD
      symptom severity and alcohol use compared to all the other typologies; Cluster 1
      demonstrated lowest risk for PTSD symptom severity and alcohol use compared to
      all other typologies; and although Clusters 2 and 3 did not differ according to
      PTSD symptom severity, individuals in Cluster 2 had significantly higher alcohol
      use. These results represent certain "at risk" versus "protective" typologies
      that may facilitate the identification of individuals at risk for comorbid PTSD
      and problematic alcohol use. (PsycINFO Database Record

PMID- 30211587
TI  - "Evaluating autonomy, beneficence, and justice with substance-using populations:
      Implications for clinical research participation": Correction to Strickland and
      Stoops (2018).
AB  - Reports an error in "Evaluating autonomy, beneficence, and justice with substance
      using populations: Implications for clinical research participation" by Justin C.
      Strickland and William W. Stoops (Psychology of Addictive Behaviors, 2018[Aug],
      Vol 32[5], 552-563). In the article, an incorrect Online First date appears in
      the article. The correct Online First publication date is July 12, 2018. The
      online version of this article has been corrected. (The following abstract of the
      original article appeared in record 2018-31276-001.) Narrow inclusion criteria
      regarding substance use are commonplace in clinical research. This is due, in
      part, to assumptions about capacity to make "rational" decisions regarding
      participation by these populations. This study evaluated decision-making and
      perceptions surrounding each of the Belmont principles among individuals with
      cocaine use histories, cigarette smokers without illicit substance use histories,
      and controls without cigarette or illicit substance use histories. Cocaine (n =
      124), cigarette (n = 128), and control (n = 145) groups were recruited using
      Amazon's Mechanical Turk. Participants completed measures evaluating research
      participation after reading two hypothetical study vignettes varying in risk.
      Assays assessed capacity to consent, perceived research burden, and endorsement
      of research participation by various populations. Individuals reporting cocaine
      use showed a reduced capacity to consent compared to controls, but this effect
      was small and largely explained by sociodemographic differences (e.g., race)
      rather than substance use history. Perceived research burden in the cigarette
      group was lower than in the cocaine group, but this difference was of a small to
      medium effect size. All groups reported substantively lower endorsement of
      research participation by individuals with illicit substance use histories
      relative to healthy adults, with less support indicated by control and cigarette
      groups compared to the cocaine group. Few differences were observed by substance
      use history regarding perceptions of and decision-making surrounding research
      participation. These data highlight the need for the continued study of evidence
      based ethics and support more widespread acceptance of research participation by
      individuals with substance use histories in clinical research. (PsycINFO Database
      Record

PMID- 30211586
TI  - Sex differences in smoking constructs and abstinence: The explanatory role of
      smoking outcome expectancies.
AB  - Scientific evidence suggests women experience more severe problems when
      attempting to quit smoking relative to men. Yet, little work has examined
      potential explanatory variables that maintain sex differences in clinically
      relevant smoking processes. Smoking outcome expectancies have demonstrated sex
      differences and associative relations with the smoking processes and behavior,
      including problems when attempting to quit, smoking-specific experiential
      avoidance, perceived barriers to quitting, and smoking abstinence. Thus,
      expectancies about the consequences of smoking may explain sex differences across
      these variables. Accordingly, the current study examined the explanatory role of
      smoking-outcome expectancies (e.g., long-term negative consequences, immediate
      negative consequences, sensory satisfaction, negative affect reduction, and
      appetite weight control) in models of sex differences across cessation-related
      problems, smoking-specific experiential avoidance, perceived barriers to
      quitting, and smoking abstinence. Participants included 450 (48.4% female; Mage =
      37.45, SD = 13.50) treatment-seeking adult smokers. Results indicated that sex
      had an indirect effect on problems when attempting to quit smoking through
      immediate negative consequences and negative affect reduction expectancies; on
      smoking-specific experiential avoidance through long-term negative consequences,
      immediate negative consequences, and negative affect reduction expectancies; on
      barriers to quitting through negative affect reduction expectancies; and on
      abstinence through appetite weight control expectancies. The current findings
      suggest that sex differences in negative affect reduction expectancies and
      negative consequences expectancies may serve to maintain maladaptive smoking
      processes, whereas appetite weight control expectancies may promote short-term
      abstinence. These findings provide initial evidence for the conceptual role of
      smoking expectancies as potential "linking variables" for sex differences in
      smoking variables. (PsycINFO Database Record

PMID- 30211588
TI  - Types of change strategies for limiting or reducing gambling behaviors and their
      perceived helpfulness: A factor analysis.
AB  - Gamblers engage with a broad range of resources and strategies to limit or reduce
      their gambling. However, there is limited research examining the uptake and
      helpfulness of the full range of strategies gamblers employ. The aim of this
      study was to compile a comprehensive inventory of change strategies and then
      group these using principal component analysis based on perceived helpfulness. We
      also aimed to determine whether there are differences in the helpfulness of
      strategies by demographic, gambling severity, and readiness indicators. The
      Change Strategies Questionnaire-Version 1 contained 99 strategies, and 489
      gamblers (including 333 problem gamblers) identified the most frequently endorsed
      strategy as remind yourself of negative consequences of gambling (92%) and think
      about how money could be better spent (92%). Principal components analysis
      identified 15 strategy groupings: cognitive, well-being, consumption control,
      behavioral substitution, financial management, urge management, self-monitoring,
      information seeking, spiritual, avoidance, social support, exclusion, planning,
      feedback, and limit finances. There were differences in the helpfulness of
      strategies by age and gambling severity. Few strategies were correlated with
      confidence to manage an urge to gamble. Overall, change strategies were viewed as
      moderately helpful. The top five strategies were all used by at least 90% of
      gamblers, and these strategies were all cognitive in nature. This study provides
      important information for the development of interventions targeting gambling
      behavior. Furthermore, it suggests that interventions for problem gambling should
      target cognitive, feedback, planning, and urge management strategies. (PsycINFO
      Database Record

PMID- 30211589
TI  - Solitary gambling mediates the risk pathway from anxiety sensitivity to excessive
      gambling: Evidence from a longitudinal ecological momentary assessment study.
AB  - Anxiety and gambling problems co-occur at high rates. Social learning theory
      (SLT) suggests that people high in anxiety engage in excessive gambling to reduce
      negative affect. Because anxiety sensitivity (AS) is a vulnerability factor
      associated with addictive behaviors, it is important to identify mediators in
      this high-risk pathway. Emerging research shows that social context mediates
      associations between anxiety vulnerability and addictive behaviors. This
      literature shows that anxiety-prone people are at increased risk for substance
      problems because they engage in frequent solitary substance use. Theory would
      predict a similar pathway to gambling problems, but this remains to be tested.
      Accordingly, this study aimed to examine solitary gambling as an explanatory
      variable in the anxiety pathway to gambling problems. We used a longitudinal
      ecological momentary assessment (EMA) design. After completing baseline measures,
      young adults (N = 108) were asked to report daily on their gambling behavior over
      a 30-day period. Bias corrected bootstrapped confidence intervals (CI) supported
      1 hypothesized indirect effect from baseline AS (Time 1) to EMA time spent
      gambling (Time 2) via EMA solitary gambling (Time 2; B = 0.019, 95% CI [0.002,
      0.045]). This suggests that emerging adults with high levels of AS at baseline
      engaged in frequent solitary gambling over the 30-day EMA sampling period, which
      in turn predicted more time spent gambling over this same time period. Our
      results show that solitary gambling mediates the relation between anxiety
      vulnerability and excessive gambling. Understanding how social context relates to
      excessive gambling can help create interventions to reduce solitary gambling
      among anxiety-prone individuals. (PsycINFO Database Record

PMID- 30211590
TI  - The impact of text orientation on form priming effects in four-character Chinese
      words.
AB  - Does visuospatial orientation influence repetition and transposed character (TC)
      priming effects in logographic scripts? According to perceptual learning
      accounts, the nature of orthographic (form) priming effects should be influenced
      by text orientation (Dehaene, Cohen, Sigman, & Vinckier, 2005; Grainger &
      Holcomb, 2009). In contrast, Witzel, Qiao, and Forster's (2011) abstract letter
      unit account argues that the mechanism responsible for such effects acts at a
      totally abstract orthographic level (i.e., the visuospatial orientation is
      irrelevant to the nature of the relevant orthographic code). The present
      experiments expanded this debate beyond alphabetic scripts and the syllabic Kana
      script used by Witzel et al. to a logographic script (Chinese). Experiment 1
      showed masked repetition and TC priming effects with primes and targets presented
      in both the conventional left-to-right horizontal orientation and the vertical
      top-to-bottom orientation, replicating Witzel et al. Experiment 2 showed masked
      repetition and TC priming effects even when both the primes and targets were
      presented in the right-to-left orientation, a rare but existent text orientation
      in Chinese. In Experiment 3, the primes, but not the targets, were presented in
      the right-to-left orientation. Priming effects were again obtained regardless of
      the fact that the primes and targets appeared in different orientations.
      Experiment 4, which involved primes and targets presented in a completely novel
      bottom-to-top orientation, also produced a TC priming effect. These results
      support abstract letter/character unit accounts of form priming effects while
      failing to support perceptual learning accounts. (PsycINFO Database Record

PMID- 30211591
TI  - Drawing enhances item information but undermines sequence information in memory.
AB  - Drawing a picture of the referent of a word produces considerably better recall
      and recognition of that word than does a baseline condition, such as repeatedly
      writing the word, a phenomenon referred to as the drawing effect. Although the
      drawing effect has been the focus of much recent research, it is not yet clear
      what underlies the beneficial effects of drawing to memory. In 3 experiments, we
      explored the roles of item and order information following drawing versus silent
      reading and produced 2 important findings. First, the drawing effect in recall
      was substantially larger when the 2 conditions were intermixed in a single list
      compared to appearing in separate lists-in other words, drawing produced a design
      effect. Second, the studied order was better retained for silent reading compared
      to drawing in pure lists. These findings are consistent with the item-order
      account: Memory for the order of drawn lists is poorer because the elaborative
      act of drawing disrupts the encoding of interitem associations (i.e., relational
      information) between all list items. Thus, the selection of an encoding task
      should be informed by how that memory might be used in the future; if one wants
      to remember individual items, then an elaborative task such as drawing is
      recommended; if one wants to remember their sequence, it is likely better to read
      silently. (PsycINFO Database Record

PMID- 30211592
TI  - When stimulus-driven control settings compete: On the dominance of categories as
      cues for control.
AB  - Stimulus-driven or reactive control refers to the modulation of attention
      poststimulus onset via retrieval of learned control settings associated with task
      stimuli. The present study asked which stimulus-driven control setting "wins" the
      competition when more than 1 is available to guide attention. Utilizing an item
      specific proportion congruence manipulation in a picture-word Stroop task, 7
      experiments examined competition between item-level and category-level control
      settings. In Experiment 1, category-level control dominated as evidenced by
      transfer of control to unique 50% congruent items (exemplars) from biased (33% or
      67% congruent) animal categories. In Experiment 2, the dominance persisted
      transfer was observed even for inconsistent transfer items (e.g., 83% congruent
      bird from a 33% congruent bird category). Recategorization of the exemplars prior
      to the Stroop task (Experiment 3a) successfully shifted the dominance to item
      level control as did changing the Stroop task goal (Experiment 4a); however,
      exposure to the exemplars (Experiment 3b) and individuation training prior to the
      Stroop task did not (Experiments 3c and 4b). These novel findings suggest
      category-level control dominates in guiding attention poststimulus onset, but
      this dominance is dependent on contextual features (i.e., mutable). We propose a
      salience account of dominance and discuss implications for item-based
      computational models. (PsycINFO Database Record (c) 2018 APA, all rights
      reserved).

PMID- 30211593
TI  - How feature relationships influence attention and awareness: Evidence from eye
      movements and EEG.
AB  - Many everyday tasks require selecting relevant objects in the visual field while
      ignoring irrelevant information. A widely held belief is that attention is tuned
      to the exact feature value(s) of a sought-after target object (e.g., color,
      shape). In contrast, subsequent studies have shown that attentional orienting
      (capture) is often determined by the relative feature(s) that the target has
      relative to other irrelevant items surrounding (e.g., redder, larger). However,
      it is unknown whether conscious awareness is also determined by relative
      features. Alternatively, awareness could be more strongly determined by exact
      feature values, which seem to determine dwelling on objects. The present study
      examined eye movements in a color search task with different types of irrelevant
      distractors to test (a) whether dwelling is more strongly influenced by exact
      feature matches than relative matches, and (b) which of the processes (capture
      vs. dwelling) is more important for conscious awareness of the distractor. A
      second experiment used an electrophysiological marker of attention (N2pc in the
      electroencephalogram of participants) to test whether the results generalize to
      covert attention shifts. As expected, the results revealed that the initial
      capture of attention was strongest for distractors matching the relative color of
      the target, whereas similarity to the target was the most important determiner
      for dwelling. Awareness was more strongly determined by the initial capture of
      attention than dwelling. These results provide important insights into the
      interplay of attention and awareness and highlight the importance of considering
      relative, context-dependent features in theories of awareness. (PsycINFO Database
      Record (c) 2018 APA, all rights reserved).

PMID- 30211594
TI  - Loneliness and social engagement in older adults: A bivariate dual change score
      analysis.
AB  - Few longitudinal studies have explored the impact of loneliness on social
      engagement. We investigated whether loneliness would result in decreased social
      engagement over time among older adults and also whether the converse, that low
      levels of social engagement would predict increases in loneliness, held.
      Additionally, we explored potential mechanisms (specifically, memory and
      depressive symptomatology as mediators) in the bidirectional relationship(s)
      between loneliness and social engagement. Data from 4,714 adults over 50 years of
      age, participating in Waves 3, 4, and 5 of the English Longitudinal Study of
      Ageing (between 2006 and 2011), were analyzed using bivariate dual change scores
      within structural equation models. Higher levels of loneliness were inversely
      associated with social engagement over time, and high levels of social engagement
      were inversely associated with loneliness over time. To address the 2nd aim, we
      used structural equation modeling to evaluate potential mediators of the
      bidirectional relationships between loneliness and changes in social engagement.
      Depressive symptomatology, semantic memory, and episodic memory were found to
      partially mediate the relationship between loneliness measured at baseline and
      social engagement 4 years later. In addition, these variables also partially
      mediated the relationship between social engagement at baseline and loneliness 4
      years later. A comparison of the 2 models revealed that the model proposing a
      pathway from loneliness to social engagement (as mediated by depressive symptoms
      and memory) provided a better fit to the data. Implications for theories of
      loneliness are discussed. (PsycINFO Database Record

PMID- 30211595
TI  - How taxonomic and thematic associations in semantic memory modulate recall in
      young through old-old adults.
AB  - The aim of the current study was to investigate how the taxonomic and thematic
      organization of semantic long-term memory affected the recall performance of
      adults and older participants on a complex semantic working memory (SWM) task.
      Taxonomic and thematic classification are the two main systems used to organize
      knowledge: taxonomic information is hierarchically structured and typically
      independent of space and time, whereas thematically grouped concepts are
      horizontal and strictly context-dependent. Generally, thematic connections (more
      intuitive and experience-based) are formed earlier in development, while
      taxonomic links (more abstract and logic-based) are acquired later. We set out to
      explore whether this developmental pattern reverses with age, hypothesizing that
      the more complex form of memory organization (i.e., taxonomic) would play a
      lesser role in facilitating recall in the old, whereas thematic organization
      would be better preserved. Participants (aged 18 to 85 years) were asked to
      recall 60 words in sets of increasing span; the words were featured in lists
      organized to force a taxonomic association, a thematic association, or no
      semantic association. The results clearly showed that task accuracy varied more
      across age groups for taxonomically linked items than for thematically linked
      ones. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 30211596
TI  - Trajectories of normal cognitive aging.
AB  - Although sensitive detection of pathological cognitive aging requires accurate
      information about the trajectory of normal cognitive aging, prior research has
      revealed inconsistent patterns of age-cognition relations with cross-sectional
      and longitudinal comparisons. Age trends in four cognitive domains were compared
      in over 5,000 adults with cross-sectional data, and in almost 1,600 adults with
      three-occasion longitudinal data. Quasi-longitudinal comparisons, which are
      similar to cross-sectional comparisons in that there is no prior test experience
      and are similar to longitudinal comparisons in that the participants are from the
      same birth cohorts, were also reported. The age trends in quasi-longitudinal
      comparisons more closely resembled those in cross-sectional comparisons than
      those in longitudinal comparisons, which suggests that, at least up until about
      age 65, age-cognition relations in longitudinal comparisons are distorted by
      prior test experience. Results from cross-sectional and quasi-longitudinal
      comparisons, which can be assumed to have minimal test experience effects, imply
      that normal cognitive aging is characterized by nearly linear declines from early
      adulthood in speed, and accelerating declines in memory and reasoning. However,
      vocabulary knowledge increased until the decade of the 60's in all three types of
      comparisons. (PsycINFO Database Record

PMID- 30211597
TI  - Motivation moderates the impact of aging stereotypes on effort expenditure.
AB  - The impact of aging stereotypes on task engagement was examined. Older adults (N
      = 144, ages 65 to 85) were exposed to primes designed to activate positive or
      negative stereotypes about aging, with half of the individuals in each stereotype
      group also assigned to a high-accountability condition to enhance motivation.
      Participants performed a memory-scan task comprising 2 levels of demands (memory
      sets of 4 or 7 items), with 2 blocks (5 min each) at each level. Systolic blood
      pressure recorded throughout the task was used to monitor engagement levels. High
      accountability was associated with greater engagement at the highest level of
      task demands. Negative stereotype activation also resulted in elevated engagement
      levels, but only during the initial trial blocks in the high-accountability
      condition. Lowest levels of engagement were associated with low accountability,
      with no difference between stereotype conditions. An analogous differential
      analysis on these same data using need for cognition and attitudes toward aging
      as measures of motivation and stereotypes revealed similar trends. Specifically,
      negative aging attitudes were associated with elevated levels of engagement only
      in individuals who were high in intrinsic motivation, with the effects greatest
      at the highest levels of task demands. The results provide a more nuanced
      perspective on the impact of negative aging stereotypes than suggested in
      previous research, with the impact on behavior moderated by situational and
      personal factors associated with motivation. Although potentially negative in the
      long run, elevated cardiovascular responses indicative of task engagement may
      represent an adaptive response to support performance. (PsycINFO Database Record

PMID- 30211598
TI  - Piloting cognitive-behavioral therapy for insomnia integrated with prolonged
      exposure.
AB  - OBJECTIVE: Approximately 35-61% of individuals with posttraumatic stress disorder
      (PTSD) report insomnia. Further, upward of 70% report clinically significant
      insomnia following PTSD treatment. There are converging lines of evidence
      suggesting that insomnia not only independently affects daytime functioning and
      worsens PTSD symptoms but also may compromise response to PTSD treatment, such as
      prolonged exposure (PE). Taken together, integrated insomnia and PTSD treatment
      may increase client-centered care and treatment outcomes. METHOD: This article
      reviews the theory and evidence for treating sleep prior to PTSD treatment,
      describes the key elements of integrated cognitive-behavioral treatment for
      insomnia (CBT-I) and PE (2NITE protocol), and presents pilot data from a sample
      of 12 treatment-seeking veterans with PTSD and insomnia who completed the 2NITE
      protocol. Sleep data were collected with sleep diaries and actigraphy watches.
      RESULTS: The Client Satisfaction Questionnaire indicated high satisfaction with
      the 2NITE protocol (mean score 29.66 out of 32 points). On average, there were
      statistical and clinically significant changes in all measures, including a 20.17
      point decrease in the PTSD Checklist DSM-5, a 11.75-point decrease in the
      insomnia severity index, an 18.58-point increase in the World Health Organization
      Quality of Life index, a 11% increase in sleep efficiency, and a 51-min increase
      in total sleep time from the actigraphy data. CONCLUSIONS: Among individuals with
      insomnia and PTSD, integrating CBT-I and PE with the 2NITE protocol represents a
      logical, innovative, and empirically informed method for augmenting existing
      treatments and optimizing outcomes that justifies further investigation.
      (PsycINFO Database Record

PMID- 30211599
TI  - PTSD and comorbid depression: Social support and self-efficacy in World Trade
      Center tower survivors 14-15 years after 9/11.
AB  - OBJECTIVE: Following the World Trade Center (WTC) terrorist attack in New York
      City, prevalence rates of posttraumatic stress disorder (PTSD) and depression
      remain elevated. Although social support and self-efficacy have been associated
      with PTSD, little is known about their differential effect on PTSD and depressive
      comorbidity. METHOD: WTC tower survivors (n = 1,304) were assessed at Wave 1
      (2003-2004), Wave 2 (2006-2007), Wave 3 (2011-2012), and Wave 4 (2015-2016).
      RESULTS: At Wave 4, 13.0% of participants had probable PTSD, a decrease from
      16.5% at Wave 1. In addition, 4.1% (54) were identified as having PTSD alone,
      6.8% (89) had depression alone, and 8.9% (116) had comorbid PTSD and depression.
      Of those with PTSD, 68.2% also had comorbid depression. WTC tower survivors with
      PTSD and comorbid depression reported greater PTSD symptom severity and were more
      likely to have had greater exposure to the events of 9/11 (adjusted odds ratio
      [aOR] = 1.14) and lower self-efficacy (aOR = 0.85) than those with depression
      alone. Less perceived social support predicted only depression and not PTSD,
      whereas less perceived self-efficacy equally predicted having PTSD or depression
      (aOR = 0.76). CONCLUSIONS: Findings indicate that self-efficacy may be more
      important to the severity and chronicity of PTSD symptoms than social support.
      Multivariate comparisons suggest that PTSD with comorbid depression is a
      presentation of trauma-dependent psychopathologies, as opposed to depression
      alone following trauma, which was independent of trauma exposure and may be
      secondary to the traumatic event and posttraumatic response. Implications for
      assessment and treatment are discussed. (PsycINFO Database Record

PMID- 30211600
TI  - Childhood maltreatment, attachment, and borderline personality-related symptoms:
      Gender-specific structural equation models.
AB  - OBJECTIVES: Survivors of early interpersonal trauma may experience relational
      problems, anger, impulsive and self-destructive behaviors, identity disturbance,
      and other difficulties that are associated with borderline personality disorder.
      Insecure attachment also has been documented in survivors and may be related to
      borderline personality-related symptoms (BPRS). The goal of the current study was
      to examine an integrative model of maternal and paternal childhood maltreatment
      and insecure attachment as they predict BPRS. METHOD: The sample was composed of
      954 participants who completed self-report measures of parental maltreatment
      during childhood, attachment security, and trauma-related symptoms. RESULTS:
      Structural equation modeling suggested differential impacts of maternal and
      paternal maltreatment on male and female participants. Both maternal and paternal
      maltreatment were directly associated with BPRS in women, whereas in men, only
      paternal maltreatment was directly related to BPRS. In women, paternal
      maltreatment was indirectly associated with BPRS through attachment anxiety but
      not through attachment avoidance. In men, maternal maltreatment was indirectly
      associated with BPRS through attachment anxiety but not through attachment
      avoidance. CONCLUSION: These findings have implications for the understanding of
      gender-specific etiologies of borderline personality symptoms and underscore
      attachment security as an important intervention target. (PsycINFO Database
      Record

PMID- 30211601
TI  - Detecting clinical and simulated dissociative identity disorder with the Test of
      Memory Malingering.
AB  - OBJECTIVE: Few studies have assessed malingering in individuals with complex
      trauma and dissociation. This is concerning because these individuals' severe and
      ranging symptoms are associated with elevations on some, but not all, validity
      scales that detect symptom exaggeration. Dissociative individuals may experience
      dissociative amnesia, yet no study to date has examined how to distinguish
      clinical from malingered amnesia with dissociative samples. The current study
      examined whether the Test of Memory Malingering (TOMM) can accurately distinguish
      patients with clinically diagnosed dissociative identity disorder (DID) and
      simulators coached to imitate DID. METHOD: Utility statistics classify
      individuals' TOMM scores as suggestive of clinical or simulated DID. TOMM scores
      from 31 patients diagnosed with DID via structured interviews were compared to
      those of 74 coached DID simulators. RESULTS: Discriminant analyses found scores
      from TOMM Trials 1 and 2 and total TOMM scores accurately classified clinical or
      simulated DID group status. In addition, TOMM Trial 1 demonstrated high
      specificity (87%) and positive predictive power (94%), as well as moderate
      sensitivity (78%), negative predictive power (63%), and overall diagnostic power
      (81%). Despite exposure to DID-specific information, simulators were not able to
      accurately feign the DID group's TOMM scores, which is inconsistent with the
      iatrogenic/sociocultural model of DID. CONCLUSION: The TOMM shows promise as
      useful in clinical and forensic contexts to detect memory malingering among DID
      simulators without sacrificing specificity. Accurate distinction between genuine
      and feigned complex trauma-related symptoms, including dissociative memory, is
      integral to the accurate diagnosis of traumatized populations. (PsycINFO Database
      Record

PMID- 30211602
TI  - Personal disability identity in retinitis pigmentosa.
AB  - PURPOSE/OBJECTIVE: Personal disability identity (PDI) refers to a positive self
      concept as a person with a disability. This study examined the reliability and
      structural validity of scores on the Personal Disability Identity Scale (PDIS;
      Hahn & Belt, 2004) and correlates of PDI in adults with retinitis pigmentosa
      (RP). Research Method/Design: Two hundred six adult participants with RP
      completed a cross-sectional online survey measuring PDI, general self-efficacy,
      mobility tool use, age at diagnosis, education level, and demographic variables.
      RESULTS: Confirmatory factor analysis (CFA) supported a two-factor model of PDI:
      denial of disability and affirmation of disability. Findings from multiple linear
      regression indicated that lower disability denial in individuals with RP was
      associated with higher general self-efficacy. Both disability denial and
      disability affirmation were associated with use of mobility tool, but not with
      age at diagnosis. CONCLUSIONS/IMPLICATIONS: Future research on disability
      identity may benefit from a separate consideration of disability denial and
      disability affirmation. Lower disability denial predicts higher general self
      efficacy in RP. Clinical implications include supporting personal disability
      acceptance rather than attempting to "normalize" individuals with disabilities.
      (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 30211603
TI  - Exploring the peer mentorship experiences of adults with spinal cord injury.
AB  - PURPOSE/OBJECTIVE: The purpose of this study was to understand the peer
      mentorship experiences of adults with spinal cord injury (SCI) through a self
      determination theory (SDT) lens. Research Method/Design: Semi-structured
      qualitative interviews were conducted with 13 adults with SCI who received
      mentorship (i.e., mentees) from fellow adults with SCI (i.e., mentors) as part of
      an existing provincial peer mentorship program. There were two analyses conducted
      in this study. The first was deductive, which involved organizing relevant data
      as per the three basic psychological needs of self-determination theory (i.e.,
      autonomy, competence, and relatedness). The second analysis was inductive and
      focused on the participants' descriptions of their experiences. RESULTS: For the
      SDT analysis, and concerning autonomy, mentees expressed they were able to make
      their own decisions and their mentors' personalized their sessions. Specific to
      relatedness, the mentees discussed that their mentors cared and empathized with
      them, which helped them connect with their mentor. In terms of competence,
      mentees explained that their mentors provided verbal encouragement and helped
      them realize they were capable of successfully completing tasks. Some mentees
      also highlighted how the mentors did not listen to their needs, indicating need
      thwarting behaviors. For the inductive analysis, mentees expressed the importance
      of their SCI community organization, the impact of mentoring on their families,
      and the positive outcomes they associated with peer mentorship, such as
      participation in daily and social activities. CONCLUSION/IMPLICATIONS: The
      present findings extend our understanding of SCI peer mentorship from the
      perspective of the mentee and particularly from an SDT angle. (PsycINFO Database
      Record (c) 2018 APA, all rights reserved).

PMID- 30211604
TI  - Exploring service dogs for rehabilitation of veterans with PTSD: A microbiome
      perspective.
AB  - PURPOSE/OBJECTIVE: Recently, there has been an increase in the use of therapy
      animals, often dogs, to assist individuals with challenges associated with
      managing stressful social situations (i.e., psychological rehabilitation).
      Potential applications are wide-ranging from elementary schools to airports to
      hospitals. Here we present an overview of the present knowledge and provide
      recommendations for future research aimed at exploring the impact of therapy dogs
      on the rehabilitation of Veterans with posttraumatic stress disorder (PTSD) with
      a focus on the microbiome. Research Method/Design: In this review we searched the
      literature for studies that were conducted involving Veterans and service dogs.
      Because of the limited number of studies, we conducted a nonsystematic review to
      include the topics of the microbiome and psychological mechanisms that may play a
      role in rehabilitation of Veterans with dogs. RESULTS: Whether dogs can be used
      as an intervention to increase function among those with PTSD remains a question.
      Nonetheless, it has been suggested that dog ownership may improve mental health
      outcomes via multiple mechanisms, such as decreasing social isolation and
      increasing physical activity and exposure to green spaces. The presence of a dog
      in the home may alter the human inhabitants' microbiomes, thereby, potentially
      providing an additional mechanism through which service dogs may influence human
      health and well-being. CONCLUSIONS/IMPLICATIONS: Theoretically, the use of
      service dogs for rehabilitation of Veterans with PTSD could improve mental health
      outcomes. To the best of our knowledge the impact that therapy dogs have on the
      microbiome of the owners, as well as their built environments, has yet to be
      explored. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 30211605
TI  - Towards an integration of the health promotion models of self-determination
      theory and theory of planned behavior among people with chronic pain.
AB  - PURPOSE: People with chronic pain and related disability often report
      motivational difficulties with engaging in health-promoting behaviors. Although
      health promotion models of self-determination theory (SDT) and theory of planned
      behavior (TPB) have been shown to explain the motivational processes behind
      health behaviors in the general population, there is limited theoretical research
      among persons with chronic pain. This study examined the integration of such
      theories relevant to physical activity and exercise behavior among pain
      populations. RESEARCH METHOD: Secondary data analyses were conducted using cross
      sectional surveys from 198 participants with chronic musculoskeletal pain
      recruited from U.S. clinics and community networks. The primary outcome was self
      reported physical activity and exercise participation. Predictor variables
      included pain intensity, functional disability, and SDT and TPB measures.
      Hierarchical regression analysis was conducted to examine the associations
      between these variables. RESULTS: Findings demonstrated that in the first step,
      functional disability was associated with physical activity and exercise; and in
      the second step, all SDT factors were associated with physical activity and
      exercise. In the final step of the model, only certain SDT and TPB factors were
      associated with physical activity and exercise. CONCLUSIONS: Despite preexisting
      pain and functional disability, the findings suggest that health behavior factors
      from both SDT and TPB are associated with physical activity and exercise
      participation. This line of research should encourage rehabilitation
      professionals to recommend regular physical activity and exercise, while
      simultaneously addressing and monitoring the SDT and TPB factors that are well
      timed and appropriate for persons with chronic pain through motivation-oriented
      rehabilitation approaches. (PsycINFO Database Record (c) 2018 APA, all rights
      reserved).

PMID- 30211606
TI  - Pain beliefs mediate relations between general resilience and dysfunction from
      chronic back pain.
AB  - PURPOSE/OBJECTIVE: A substantial percentage of people affected by chronic back
      pain maintain a high quality of life despite ongoing discomfort. Presumably, more
      resilient persons view pain and their capacities to manage it in a manner that
      mitigates pain-related dysfunction. Research Method/Design: To test this premise,
      307 mainland Chinese adults with chronic back pain (189 women, 118 men) completed
      self-report measures of psychological resilience, pain beliefs (challenge
      appraisals of pain, pain self-efficacy, pain catastrophizing) and pain-related
      dysfunction (i.e., pain intensity, disability, affective distress, depression)
      within a cross-sectional research design. RESULTS: Structural equation modeling
      indicated elevations in general psychological resilience were related to more
      frequent appraisals of pain as a challenge, higher pain self-efficacy levels, and
      lower pain catastrophizing levels. In turn, resilience, pain self-efficacy, and
      pain catastrophizing were linked to pain-related dysfunction while challenge
      appraisals were not. CONCLUSIONS/IMPLICATIONS: Together, results underscored
      specific pain beliefs underlying the pathway between resilience and reduced
      dysfunction from chronic back pain. Aside from evaluating dysfunctional
      expectancies (e.g., pain catastrophizing) and outcomes, practitioners and
      researchers should consider beliefs about personal effectiveness in managing pain
      within assessment and treatment protocols of chronic back pain. (PsycINFO
      Database Record (c) 2018 APA, all rights reserved).

PMID- 30211607
TI  - Early recovery following traumatic brain injury and alcohol withdrawal
      management.
AB  - PURPOSE: To compare recovery experienced during inpatient rehabilitation among
      individuals with traumatic brain injury (TBI) based on whether their acute care
      included the Clinical Institute Withdrawal Assessment for Alcohol (CIWA)
      protocol. DESIGN: Participants included 234 individuals with TBI who completed
      inpatient rehabilitation at a TBI Model Systems site. Of these, 67 patients were
      treated using the CIWA protocol (TBI + CIWA); 167 patients were treated for TBI
      alone (TBI only). Demographic, injury, and treatment variables between the 2
      groups were compared. A repeated-measures analysis of variance (ANOVA) compared
      Disability Rating Scale (DRS) scores between the groups at admission and
      discharge from inpatient rehabilitation. RESULTS: The 2 groups did not
      significantly differ on DRS scores at admission to inpatient rehabilitation: TBI
      + CIWA, M = 9.6 (SD = 3.5) vs. TBI only, M = 10.1 (SD = 4.2). There was a
      significant difference in DRS scores at discharge, with the TBI + CIWA group
      having lower scores: TBI + CIWA, M = 6.4 (SD = 1.9) vs. TBI only, M = 7.0 (SD =
      2.2). A repeated-measures ANOVA of DRS scores from admission to discharge
      revealed a significant between-subjects effect based on patients' Mississippi
      categorization of posttraumatic amnesia (PTA) duration (p < .001) and age (p =
      .016) but not based on their CIWA status (p = .068). A post hoc comparison
      including age as a covariate revealed a significant difference based on CIWA
      status (p = .013) within the "moderate" injury group at discharge, with the TBI +
      CIWA group having lower discharge DRS scores. CONCLUSIONS: Given the significant
      symptom overlap between alcohol withdrawal and PTA, it is likely that these 2
      delirium presentations are confounded during the initial recovery from TBI,
      leading to "overestimation" of injury severity-particularly among individuals
      with moderate TBI. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 30211608
TI  - Electrophysiological correlates of empathic processing and its relation to
      psychopathic meanness.
AB  - OBJECTIVE: A lack of empathy and the presence of predatory tendencies are
      considered key features of psychopathic meanness. Previous electrophysiological
      studies on empathy in relation to psychopathic traits have focused mainly on
      empathy for pain; therefore, little is known about the electrophysiological
      correlates of empathy in aggressive situations that are particularly relevant for
      psychopathic meanness. METHOD: We employed electroencephalography in a community
      sample (n = 70), the majority of whom had attained a higher level of education.
      All participants were screened for not having psychiatric conditions or criminal
      history. The P3 and late positive potential (LPP) event-related potentials and mu
      rhythm suppression were examined as indices of empathic processing during the
      observation of situations in which victims of aggression were depicted. RESULTS:
      As predicted, it was found that persons with elevated levels of psychopathic
      meanness scored lower on trait empathy and assigned higher positive valence to
      the aggression scenes. It is interesting that those scoring higher on meanness
      also scored higher on empathy for the perpetrator. In addition, it was found that
      psychopathic meanness was negatively related to LPP amplitudes following pictures
      of aggressive situations. No significant associations were found between meanness
      and the P3 or between meanness and mu suppression. CONCLUSIONS: This study was
      the first to assess the electrophysiological signature of empathy during the
      processing of pictures depicting aggressive situations and the relationships with
      psychopathic meanness. The outcomes highlight the need for more integrative
      approaches to further study the complex pattern of relationships between empathy
      and psychopathic meanness. (PsycINFO Database Record (c) 2018 APA, all rights
      reserved).

PMID- 30211610
TI  - Intraindividual variability in neuropsychological performance predicts cognitive
      decline and death in HIV.
AB  - OBJECTIVE: HIV-associated neurocognitive disorder (HAND) occurs in a significant
      percentage of HIV-infected (HIV+) adults. Increased intraindividual variability
      (IIV) in cognitive function may be an early marker of emerging neurocognitive
      disorder, which suggests that IIV may be a sensitive measure of neurologic
      compromise in HIV. In the current study, we hypothesize that increased IIV may
      predict impending morbidity, including future cognitive decline and death.
      METHOD: In 708 HIV+ participants followed longitudinally for up to 14 years, we
      assessed the role of dispersion in forecasting death and cognitive decline.
      Incident neurocognitive impairment was predicted in a mixed-effects ordinal
      logistic regression model using age, gender, baseline mean cognitive functioning,
      CD4+, time followed, years of education, and dispersion at the previous visit.
      Death before the next visit was predicted in a binomial mixed-effects regression
      model using age, gender, baseline mean cognitive functioning, CD4+, time
      followed, years of education, and dispersion. RESULTS: Point-in-time dispersion
      and change in dispersion between visits predict future cognitive decline and
      death in HIV+ individuals. Individuals with greater dispersion at a visit or who
      had larger changes in dispersion between visits were more likely to demonstrate
      greater neurocognitive impairment at the subsequent visit. Greater IIV was also
      associated with an increased risk of death prior to the subsequent visit, even
      after controlling for HAND severity and global cognitive functioning.
      CONCLUSIONS: We conclude that the IIV in cognitive functioning may be more
      predictive of future disease consequence than mean level of cognitive
      functioning. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 30211609
TI  - Dorsolateral prefrontal cortex volume as a mediator between socioeconomic status
      and executive function.
AB  - OBJECTIVE: Lower socioeconomic status (SES) is related to poorer cognitive
      performance, but the neural underpinnings of this relation are not fully
      understood. This study examined whether SES-linked decrements in executive
      function were mediated by smaller dorsolateral prefrontal cortex (DLPFC) volumes.
      Given the literature demonstrating that SES-brain relations differ by race, we
      examined whether race moderated these mediations. METHOD: Participants were 190
      socioeconomically diverse, self-identified African American (AA) and White adults
      from the Healthy Aging in Neighborhoods of Diversity across the Life Span
      (HANDLS) SCAN study. Regional brain volumes were derived using T1-weighted MP
      RAGE images. Adjusting for age and sex, moderated mediation analyses examined if
      the DLPFC mediated SES-executive function relations differently across racial
      groups. Executive function was measured using Trail Making Test part B (Trails
      B), Digit Span Backwards (DSB), and verbal fluency. RESULTS: Moderated mediation
      demonstrated that DLPFC volume significantly mediated the association between SES
      and Trails B in Whites (lower confidence interval [CI] = 0.01; upper CI = 0.07),
      but not in AAs (lower CI = -0.05; upper CI = 0.01). No mediations were found for
      DSB or verbal fluency, although SES was related to all tests. CONCLUSION: The
      DLPFC may be important in the association of SES and mental flexibility for
      White, but not AA adults. It is possible that the well-replicated advantages of
      high SES among Whites do not readily translate, on average, to AAs. These
      findings highlight the importance of brain volume for cognitive functioning,
      while adding to the literature on sociodemographic health disparities. (PsycINFO
      Database Record (c) 2018 APA, all rights reserved).

PMID- 30211611
TI  - Hearing loss and verbal memory assessment among older adults.
AB  - OBJECTIVE: Research has found that adults with hearing loss perform worse on
      cognitive testing than adults without hearing loss; however, heavy emphasis on
      tests involving auditory stimuli may overdiagnose cognitive impairment among
      individuals with hearing loss. This study compared visual- and auditory-verbal
      memory tests among adults with and without hearing loss. METHOD: Forty-one adults
      with hearing loss (HL) and 41 age-matched adults with normal hearing (NH)
      completed a neuropsychological battery that included auditory and visual versions
      of the Hopkins Verbal Learning Testing-Revised (HVLT-R). A natural auditory
      condition presented HVLT-R stimuli at normal speaking volume. A crossed auditory
      condition presented HVLT-R stimuli to individuals with hearing loss with
      amplified acoustic intensity and to individuals with normal hearing under hearing
      loss simulation. RESULTS: Mixed-model ANOVA indicated significant group (HL vs.
      NH) by condition (visual, natural auditory, crossed auditory) interactions for
      HVLT-R performance, with large effect sizes. The HL group performed significantly
      worse than the NH group on the natural auditory version; however, the NH group
      performed significantly worse than the HL group on the crossed condition. The
      groups were equivalent on the visual condition and all other cognitive tests,
      showing small effect sizes. Moreover, for the HL group, visual HVLT-R correlated
      with other cognitive tests whereas auditory versions did not. CONCLUSION:
      Cognitively intact older adults with hearing loss appeared impaired on auditory
      verbal memory assessment under typical administration conditions. Visual
      assessment of verbal memory showed evidence of superior validity and is a viable
      alternative method to assess memory function especially in older populations.
      (PsycINFO Database Record

PMID- 30211613
TI  - Quercetin in Idiopathic Pulmonary Fibrosis: Another Brick in the Senolytic Wall.

PMID- 30211612
TI  - Executive impairment is associated with unawareness of neuropsychiatric symptoms
      in premanifest and early Huntington's disease.
AB  - OBJECTIVE: Unawareness of neuropsychiatric symptoms appears to be common in
      Huntington's disease (HD), but the clinical correlates of unawareness are
      unclear. Identifying predictors of unawareness is important for improving
      diagnosis of neuropsychiatric symptoms, and cognitive impairment, specifically
      executive impairment, may be a potential important predictor of unawareness. The
      authors examined whether unawareness of neuropsychiatric symptoms is more common
      in early HD compared to premanifest HD, and whether executive task performance
      was associated with awareness, independent of demographic, motor or mood
      variables. METHOD: One hundred thirty-two gene-positive participants (60
      premanifest and 72 early diagnosed) from the multicenter TRACK-HD study were
      included. Participants and their informants completed self and informant versions
      of the Frontal Systems Behavior Scale, which measures executive dysfunction,
      apathy, and disinhibition symptoms. Awareness was measured as the discrepancy
      between self- and informant-reports across premanifest and early HD groups.
      Participants' executive task performance was then assessed as a predictor of
      unawareness across the whole group. RESULTS: Premanifest participants reported
      higher levels of executive dysfunction, apathy and disinhibition than their
      informants, whereas early HD participants reported less executive dysfunction and
      apathy than their informants, indicating that unawareness is more common after
      diagnosis. Impaired executive task performance was related to unawareness of
      executive dysfunction and apathy, independent of demographic, motor and mood
      variables. CONCLUSIONS: Executive impairment is a useful early predictor of
      unawareness of neuropsychiatric symptoms in HD. Clinicians should closely monitor
      HD patients with executive impairment for unawareness, and consider this when
      assessing neuropsychiatric symptoms in HD and providing education to patients and
      families. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 30211615
TI  - Silica Exposure, Silicosis, and the New Occupational Safety and Health
      Administration Silica Standard. What Pulmonologists Need to Know.

PMID- 30211614
TI  - Reply to: Supplemental Oxygen in Obstructive Sleep Apnea: Much to Be Done.

PMID- 30211616
TI  - Minimal Important Difference for Physical Activity and Validity of the
      International Physical Activity Questionnaire in ILD.
AB  - RATIONALE: The optimal method of physical activity measurement has not been
      determined in patients with fibrotic interstitial lung disease (ILD). OBJECTIVES:
      To assess the validity, internal consistency, and responsiveness of the
      International Physical Activity Questionnaire long form (IPAQ-LF) and to estimate
      the minimal important difference (MID) for moderate-to-vigorous physical activity
      (MVPA) in patients with fibrotic ILD. METHODS: This two-centre prospective cohort
      study included a convenience sample of 111 outpatients with fibrotic ILD who wore
      waist and wrist ActiGraph accelerometers for seven consecutive days, followed by
      self-administration of the IPAQ-LF. Both measurements were performed at baseline
      and 6-month follow-up. Spearman rank correlations were used to evaluate the IPAQ
      LF validity in comparison to activity monitor data, lung function, step count,
      and quality of life. The internal consistency of the IPAQ-LF was determined using
      Cronbach's alpha. Self-reported changes in IPAQ-LF parameters were compared among
      tertiles of change measured by the waist activity monitor to assess the
      responsiveness of the IPAQ-LF after 6 months. Anchor- and distribution-based
      methods were used to estimate the MID for MVPA. RESULTS: Self-reported MVPA
      minutes, activity-related energy expenditure, sedentary time, and inactive time
      of the IPAQ-LF generally showed moderate-to-strong correlations with
      corresponding waist activity monitor data, step count, lung function, and quality
      of life. The Cronbach's alpha of the IPAQ-LF was 0.78. The IPAQ-LF was responsive
      at detecting increases in weekly MVPA and energy expenditure. The MIDs for MVPA
      were 8-26 and 13-58 minutes/week using the anchor-based method for waist activity
      monitor and IPAQ-LF data, respectively. The distribution-based MID estimate for
      MVPA was 104-242 minutes/week. CONCLUSIONS: The IPAQ-LF has acceptable validity
      and internal consistency for measuring daily physical activity in patients with
      fibrotic ILD. The IPAQ-LF was responsive at detecting increases in physical
      activity, but limited in its ability to detect declines or changes in inactivity.
      Using an anchor-based approach, the MID for MVPA measured by a waist activity
      monitor is approximately 26 minutes/week.

PMID- 30211617
TI  - The Differential Influence of Early Life Weight Gain on Asthma Risk in Later
      Childhood.

PMID- 30211618
TI  - Physiological Analysis and Clinical Performance of the Ventilatory Ratio in Acute
      Respiratory Distress Syndrome.
AB  - RATIONALE AND OBJECTIVES: Pulmonary dead space fraction is an independent
      predictor of mortality in acute respiratory distress syndrome (ARDS). Yet, it is
      seldom utilized in practice. The Ventilatory ratio is a simple bedside index that
      can be calculated using routinely measured respiratory variables and is a measure
      of impaired ventilation. Ventilatory ratio is defined as [minute ventilation
      (mL/min) * arterial PCO2 (mmHg)]/[predicted body weight * 100 * 37.5]. The
      relation of Ventilatory Ratio with in ARDS is currently unknown. METHODS: First,
      in a single-center, prospective observational study of ARDS, we tested the
      association of with Ventilatory Ratio. With in-hospital mortality as the primary
      outcome and ventilator-free days as the secondary outcome, we tested the role of
      Ventilatory Ratio as an outcome predictor. The findings from this study were
      further verified in secondary analyses of two NHLBI ARDS Network randomized
      controlled trials. MEASUREMENTS AND MAIN RESULTS: Ventilatory Ratio positively
      correlated with . Ordinal groups of Ventilatory Ratio had significantly higher .
      Ventilatory Ratio was independently associated with increased risk of mortality
      after adjusting for PaO2/FiO2, and PEEP (OR 1.51, p = 0.024) and after adjusting
      for APACHE II score (OR 1.59, p=0.04). These findings were further replicated in
      secondary analyses of two separate NHLBI randomized controlled trials.
      CONCLUSIONS: Ventilatory Ratio correlates well with in ARDS and higher values at
      baseline are associated with increased risk of adverse outcomes. These results
      are promising for the use of Ventilatory Ratio as a simple bedside index of
      impaired ventilation in ARDS.

PMID- 30211619
TI  - Supplemental Oxygen in Obstructive Sleep Apnea: Much to Be Done.

PMID- 30211621
TI  - Future of Helicobacter pylori and its feasibility.

PMID- 30211620
TI  - Applying behavioral activation to sustain and enhance the effects of contingency
      management for reducing stimulant use among individuals with HIV infection.
AB  - There is a high prevalence of stimulant use among HIV-infected individuals, which
      is associated with suboptimal antiretroviral therapy (ART) adherence, HIV
      treatment interruptions, detectable HIV viral load, and transmission of HIV via
      increased sexual risk behavior. Contingency management (CM) is an initially
      effective treatment for stimulant use. However, the effects of CM are not
      sustained after the active intervention has ended. One potential contributor to
      the intractability of existing treatments may be a lack of attention to
      replacement activities or the role of depressed mood. Behavioral activation (BA)
      is an evidence-based approach for depression that involves identifying and
      participating in pleasurable, goal-directed activities. As a potential approach
      to address the CM rebound effect - informed by our formative qualitative research
      with the participant population - we conducted an open pilot trial of an
      intervention combining CM-BA for HIV-infected individuals with stimulant use
      disorder. Participants completed weekly BA therapy sessions (10-16 sessions) and
      thrice-weekly toxicology screenings (12 weeks); contingencies were rewarded for
      negative toxicology tests to support reengagement into positive life activities.
      Major assessments were conducted at baseline, 3-, and 6-months. Toxicology
      screening was repeated prior to the 6-month assessment. Eleven participants with
      stimulant use disorder enrolled; 7 initiated treatment and completed the full
      intervention. The mean age was 46 (SD = 5.03) and 14% identified as a
      racial/ethnic minority. Of the completers, the mean change score in self-reported
      stimulant use within the past 30 days (within-person change; reduction in self
      reported stimulant use) was 4.14 days at 3 months and 5.0 days at 6 months
      [Cohen's d = 0.89]. The mean change score in weekly toxicology screens (reduction
      in positive toxicology screens) was .71 at 3 months and 1 at 6 months [Cohen's d
      = 1.05]. Exit interviews indicated that the integrated intervention was well
      received and acceptable. This study provides preliminary evidence that a combined
      CM-BA intervention for this population was feasible (100% retention at 6-months),
      acceptable (100% of intervention sessions attended; participants rated the
      intervention 'acceptable' or 'very acceptable'), and may be an option to augment
      the potency and sustained impact of CM for this population. Future pilot testing
      using a randomized controlled design is warranted.

PMID- 30211623
TI  - Exosome-derived miRNAs as predictive biomarkers for diffuse large B-cell lymphoma
      chemotherapy resistance.
AB  - AIM: To analyze the expression profiles, clinicopathological features and
      chemotherapeutic efficacies of exosome-derived miRNAs in diffuse large B-cell
      lymphoma (DLBCL). MATERIALS & METHODS: Next-generation sequencing technique was
      performed to identify miRNA profiles in exosomes from parental and chemoresistant
      DLBCL cells. The results were validated by quantitative real-time PCR, and
      further analyzed by bioinformatics and statistical methods. RESULTS: We
      identified 37 significantly upregulated and 17 downregulated miRNAs. Of four
      upregulated miRNAs validated, we found miR-99a-5p and miR-125b-5p were
      significantly upregulated. Increased levels of exosomal miR-99a-5p and miR-125b
      5p in DLBCL patients' serum were associated with shorter progression-free
      survival time, and they can predict chemotherapeutic efficacy. CONCLUSION:
      Exosomal miR-99a-5p and miR-125b-5p can serve as biomarkers for DLBCL.

PMID- 30211622
TI  - The 19q13 KRAB Zinc-finger protein ZFP82 suppresses the growth and invasion of
      esophageal carcinoma cells through inhibiting NF-kappaB transcription and
      inducing apoptosis.
AB  - AIM: To study the epigenetic alternations and biological functions of ZFP82 in
      esophageal squamous cell carcinoma. MATERIALS & METHODS: Analysis of ZFP82
      expression was carried out by quantitative real-time PCR. Cell function was
      tested by MTS cell proliferation assay, transwell assay and flow cytometry. Gene
      mechanisms were studied by Reverse Transcription-Polymerase Chain Reaction (RT
      PCR), quantitative real-time PCR, luciferase reporter assay and Western blot.
      RESULTS: ZFP82 promoter methylation was downregulated in esophageal squamous cell
      carcinoma. ZFP82 ectopic expression suppressed cell function and regulated NF
      kappaB phosphorylation and genes involved in cell cycle arrest and apoptosis.
      Moreover, ZFP82 methylation was correlated with age, tumor stage and outcome.
      CONCLUSION: ZFP82 is a tumor suppressor and is disrupted by promoter CpG
      methylation during esophageal carcinogenesis.

PMID- 30211624
TI  - A Comparison of the Descriptive Information from the MMPI-2 and MMPI-2-RF.
AB  - Do MMPI-2 or MMPI-2-RF profiles differ in how accurately they depict examinees?
      To explore this question, we examined differences in clinical descriptions of
      equivalent profiles from the two instruments. Fourteen valid MMPI-2 protocols
      from an archival private practice sample were scored as both the MMPI-2 and the
      MMPI-2-RF. The resulting 28 profiles were coded separately by four raters using
      the Midwestern Q-Sort. Examinee descriptions from the two instruments were
      compared in terms of their (a) similarity, operationalized by q-correlations
      between corresponding MMPI-2 and MMPI-2-RF ratings; (b) descriptive validity,
      operationalized by correlations with q-sorts provided by the examinees'
      therapists; and (c) incremental descriptive validity, operationalized by
      incremental prediction of the therapist q-sorts by the MMPI-2 and MMPI-2-RF, one
      over the other. Descriptions from corresponding MMPI-2 and MMPI-2-RF score
      reports were highly intercorrelated. Ratings from both were valid predictors of
      therapist descriptions, and neither clearly outperformed the other in terms of
      incremental validity.

PMID- 30211625
TI  - Current Therapeutic Management of Perinatal Stroke with a Focus on the Upper
      Limb: A Cross-Sectional Survey of UK Physiotherapists and Occupational
      Therapists.
AB  - AIM: To determine current UK pediatric physiotherapist (PT) and occupational
      therapist (OT) management of perinatal stroke. DESIGN: Web-based cross-sectional
      survey. METHODS: Participants were members of the Association of Paediatric
      Chartered Physiotherapists and Occupational Therapists specialist section:
      children young people and families working with infants. Items covered
      prioritization of referrals, assessments, therapy approaches aimed at the upper
      limb, and parental support. RESULTS: 179 therapists responded. 87.2% of PTs and
      63.0% of OTs managed infants with perinatal stroke. Infants with clinical signs
      of motor dysfunction at referral were prioritized for early initial assessment.
      The most frequently used assessments were the Alberta Infant Motor Scale (AIMS)
      and Bayley Scales of Infant Development (BSID). Of PTs and OTs, 41.9 and 40.0%
      used no standardized assessments. Frequently used therapy interventions were
      Bobath/Neurodevelopmental Therapy (NDT), positioning aids and passive movements.
      88.1% of therapists would choose a bilateral rather than unilateral (affected
      side) therapy approach for infants with perinatal stroke aged up to 6 months. Of
      PTs and OTs, 56.9 and 57.1% provided psychological support to families.
      CONCLUSIONS: Assessment and provision of therapy services following perinatal
      stroke is variable. Increased use of standardized assessments and centralized
      data collection regarding service provision for high-risk infants is recommended.

PMID- 30211626
TI  - Why an Aging Smoker Lung Develops IPF and Not COPD?
AB  - Idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease
      (COPD) are generally progressive and irreversible chronic-degenerative disorders.
      COPD is associated with chronic inflammation, and changes in both the alveolar
      and airway compartments, resulting in small airways disease and emphysema. IPF is
      driven by an abnormal activation of the alveolar lung epithelium resulting in
      progressive scarring of the lung parenchyma. Both diseases are heterogeneous with
      several clinical phenotypes, and usually occur in aged individuals, mostly
      smokers. Although drastically different but similarly devastating, COPD and IPF
      share a number of accelerating lung aging processes, smoking injury and even some
      convergent molecular pathways. A key question remains why an older smoking
      individual develops IPF instead of COPD? Moreover, why do some individuals
      develop both diseases? Here we examine the common and divergent pathogenic
      mechanisms, highlighting the distinct relevant self-determining molecular
      mechanisms that made the pathological pathways and outcome radically different.

PMID- 30211627
TI  - Survivin IPF: Targeting Cellular Metabolism to Promote Apoptosis in IPF
      Fibroblasts.

PMID- 30211628
TI  - Localization and translation control of slam in Drosophila cellularization.
AB  - In this extra view, we comment on our recent work concerning the mRNA
      localization of the gene slow as molasses (slam). slam is a gene essential for
      the polarized invagination of the plasma membrane and separation of basal and
      lateral cortical domains during cellularization as well as for germ cell
      migration in later embryogenesis. We have demonstrated an intimate relationship
      between slam RNA and its encoded protein. Slam RNA co-localizes and forms a
      complex with its encoded protein. Slam mRNA localization not only is required for
      reaching full levels of functional Slam protein but also depends on Slam protein.
      The translation of slam mRNA is subject to tight spatio-temporal regulation
      leading to a rapid accumulation of Slam protein and zygotic slam RNA at the
      furrow canal. In this extra view, we first discuss the mechanism controlling
      localization and translation of slam RNA. In addition, we document in detail the
      maternal and zygotic expression of slam RNA and protein and provide data for a
      function in membrane stabilization. Furthermore, we mapped the region of Slam
      protein mediating cortical localization in cultured cells.

PMID- 30211630
TI  - Psychometric Properties of the Multidimensional Scale of Perceived Social Support
      in Greek Nurses.
AB  - Background Psychosocial well-being in the workplace may increase retention of
      oncology nurses, while a lack of social support has been a predictor of
      occupational stress in nurses. Purpose To further explore this phenomenon by
      examining the psychometric properties of the Multidimensional Scale of Perceived
      Social Support in Greek nurses working in oncology and mental health settings.
      Methods A cross-sectional design was used. The sample consisted of 150 nurses (70
      oncology nurses and 80 mental health nurses) from the area of greater Athens who
      joined the study. The scale was translated to Greek using the "forward-backward"
      procedure. The Multidimensional Scale of Perceived Social Support's internal
      consistency reliability (Cronbach's alpha), stability (intraclass correlation
      coefficient), factor structure (factor analysis), and convergent validity
      (correlation with Ways of Coping Questionnaire) were examined. Results A three
      factor (significant others, family, and friends) model was confirmed. The
      subscales representing the three factors demonstrated excellent internal
      consistency reliability (Cronbach's alphas > .90) and stability intraclass
      correlation coefficient (>.90). Conclusions The measure is reliable and valid,
      and it can be used to assess nurses' social support; the results of such an
      assessment could be helpful when selecting strategies for assisting nurses.

PMID- 30211629
TI  - Toll-like Receptor 3 is a Therapeutic Target for Pulmonary Hypertension.
AB  - RATIONALE: Pulmonary arterial hypertension (PAH) is characterized by vascular
      cell proliferation and endothelial cell apoptosis. Toll-like receptor 3 (TLR3) is
      a receptor for double-stranded RNA and has been recently implicated in vascular
      protection. OBJECTIVE: The goal was to study the expression and role of TLR3 in
      PAH and to determine whether a TLR3 agonist reduces Pulmonary Hypertension in
      preclinical models. METHODS: Lung tissue and endothelial cells from PAH patients
      were investigated by polymerase chain reaction, immunofluorescence and apoptosis
      assays. TLR3-/- and TLR3+/+ mice were exposed to chronic hypoxia and SU5416.
      Chronic hypoxia or chronic hypoxia/SU5416 rats were treated with the TLR3 agonist
      polyinosinic:polycytidylic acid [Poly(I:C)]. MEASUREMENTS AND MAIN RESULTS: TLR3
      expression was reduced in PAH patient lung tissue and endothelial cells, and TLR3
      /- mice exhibited more severe Pulmonary Hypertension following exposure to
      chronic hypoxia/SU5416. TLR3 knockdown promoted double-stranded RNA signaling via
      other intracellular RNA receptors in endothelial cells and this was associated
      with greater susceptibility to apoptosis, a known driver of pulmonary vascular
      remodeling. Poly(I:C) increased TLR3 expression via interleukin-10 in rat
      endothelial cells. In vivo, high dose Poly(I:C) reduced Pulmonary Hypertension in
      both rat models in proof-of-principle experiments. In addition, Poly(I:C) also
      reduced right ventricular failure in established Pulmonary Hypertension.
      CONCLUSIONS: Our work identifies a novel role for TLR3 in PAH based on the
      findings that reduced expression of TLR3 contributes to endothelial apoptosis and
      pulmonary vascular remodeling.

PMID- 30211631
TI  - The Musical Eulogy and Other Functions of Funeral Music.
AB  - This article examines the function of music during contemporary funerals in the
      Netherlands. Using a performance-based approach, this article shows that music
      adds to the ritual dimension of contemporary funerals, by relating the music to
      the funeral itself, the deceased person's identity, and to emotions. Zooming in
      on the music that in contemporary personalized funerals is selected because it is
      one way or another-related to the deceased, it will be shown that the lyrical
      content of this music is less important than social and emotional aspects.
      Theoretically, the concept of the musical eulogy is introduced as a hermeneutic
      tool to examine music in ritualized contexts.

PMID- 30211632
TI  - "As if Nothing Happened": Experiences of Bereaved Parents in Romania.
AB  - Prior research has found high levels of distress in parents who experience the
      death of a child; however, Romanian parents, whose experiences are influenced by
      the nation's shared historical trauma, have not been studied. This mixed-methods
      study found very high levels of distress in a sample of 237 bereaved parents in
      Romania, primarily women. Specifically, 89% of respondents scored above the
      clinical cutoff for trauma responses, 66% did so for anxious responses, and 82%
      did so for depressive responses. Qualitative analyses of respondents' narratives
      suggest that, through complex interactions between political, social, and medical
      systems, the lack of care after the death of a child seems to incite additional
      distress in parents. These findings warrant further exploration of traumatic
      grief in Romania, especially in the context of historical and political trauma,
      and of ways in which support can be provided to grieving parents in this unique
      cultural milieu.

PMID- 30211633
TI  - Recombinase Polymerase Amplification Assay for Field Detection of Tomato
      Bacterial Spot Pathogens.
AB  - Bacterial spot of tomato is caused by Xanthomonas gardneri, X. euvesicatoria, X.
      perforans, and X. vesicatoria. Current diagnostic methods for the pathogens are
      not in-field assays. Recombinase polymerase amplification (RPA) is ideal for in
      field detection assays because it is an isothermal technique that is rapid and
      more tolerant to inhibitors compared to PCR. Hence, novel RPA probes and primers
      were designed to amplify regions of the hrcN gene of X. gardneri, X.
      euvesicatoria, and X. perforans. The X. gardneri RPA is specific to X. gardneri
      with a detection limit of 106 CFU/ml, and detected X. gardneri in lesions from
      naturally (n=6) or artificially (n=18) infected plants. The X. euvesicatoria RPA
      detects both X. euvesicatoria and X. perforans with a detection limit of 106
      CFU/ml and detected both pathogens in plants artificially infected (n=36) or
      naturally infected (n=85) with either X. euvesicatoria or X. perforans. The X.
      perforans RPA is specific to X. perforans with a detection limit of 107 CFU/ml.
      Although the X. perforans RPA assay was unable to detect X. perforans from
      lesions, the X. euvesicatoria RPA was successfully used in-field to detect X.
      perforans from symptomatic field samples (n=31). The X. perforans RPA was then
      used to confirm the pathogen in the lab. The X. euvesicatoria and X. gardneri RPA
      is promising for rapid, real-time in-field detection of bacterial spot and one of
      the first developed among plant pathogenic bacteria.

PMID- 30211634
TI  - Quantitative Trait Loci Conferring Leaf Rust Resistance in Hexaploid Wheat.
AB  - Leaf rust, caused by the fungal pathogen Puccinia triticina, is a major threat to
      wheat production in many wheat-growing regions of the world. The introduction of
      leaf rust resistance genes into elite wheat germplasm is the preferred method of
      disease control, being environmentally friendly and crucial to sustained wheat
      production. Consequently, there is considerable value in identifying and
      characterizing new sources of leaf rust resistance. While many major, qualitative
      leaf rust resistance genes have been identified in wheat, a growing number of
      valuable sources of quantitative resistance have been reported. Here we review
      the progress made in the genetic identification of quantitative trait loci (QTL)
      for leaf rust resistance detected primarily in field analyses, i.e., adult plant
      resistance. Over the past 50 years, leaf rust resistance loci have been assigned
      to genomic locations through chromosome analyses and genetic mapping in
      biparental mapping populations, studies that represent 79 different wheat leaf
      rust resistance donor lines. In addition, seven association mapping studies have
      identified adult plant and seedling leaf rust resistance marker trait
      associations in over 4,000 wheat genotypes. Adult plant leaf rust resistance QTL
      have been found on all 21 chromosomes of hexaploid wheat, with the B genome
      carrying the greatest number of QTL. The group 2 chromosomes are also
      particularly rich in leaf rust resistance QTL. The A genome has the lowest number
      of QTL for leaf rust resistance. Copyright (c) 2018 The Author(s). This is an
      open access article distributed under the CC BY-NC-ND 4.0 International license .

PMID- 30211635
TI  - Investing in our future: An update on the student debt issue.

PMID- 30211636
TI  - Who should you turn to for help managing behavior problems in small animal
      practice?

PMID- 30211637
TI  - Retrospective analysis of incidence, clinical features, potential risk factors,
      and prognostic indicators for aspiration pneumonia in three brachycephalic dog
      breeds.
AB  - OBJECTIVE To investigate incidence, clinical features, potential risk factors,
      and prognostic indicators for aspiration pneumonia in Pugs, French Bulldogs, and
      Bulldogs. DESIGN Retrospective, observational study. ANIMALS 41 brachycephalic
      dogs with aspiration pneumonia. PROCEDURES Medical records of a veterinary
      referral hospital were retrospectively searched to identify Pugs, French
      Bulldogs, and Bulldogs treated for aspiration pneumonia between 2006 and 2015.
      Signalment, clinical data, and outcomes were recorded. Variables of interest were
      analyzed for statistical associations with outcome. Incidence of aspiration
      pneumonia for the population of interest was compared with that for all other dog
      breeds and for the general hospital population of dogs during the study. RESULTS
      41 of 2,141 (1.91%) dogs of the selected brachycephalic breeds and 396 of 80,137
      (0.49%) dogs overall had a diagnosis of aspiration pneumonia. Relative risk of
      the disease in the population of interest was 3.77 times that for all other
      breeds. Median age at disease onset was greater for Pugs (83 months) than for
      French Bulldogs (8 months) and Bulldogs (6 months). History of gastrointestinal
      signs was the most commonly observed preidentified risk factor (27/41 [66%]) in
      these breeds. Neurologic disease was significantly more common in Pugs than in
      French Bulldogs and Bulldogs. On univariate analysis, increased age, male sex,
      obtundation, hypoalbuminemia, azotemia, and high liver enzyme activities were
      associated with nonsurvival; on logistic regression, increased age was associated
      with nonsurvival. CONCLUSIONS AND CLINICAL RELEVANCE Age at onset and presence of
      other risk factors for aspiration pneumonia may vary among brachycephalic dog
      breeds. Prospective studies are needed to determine common risk factors and
      prognostic indicators for aspiration pneumonia in the larger population of
      brachycephalic dogs.

PMID- 30211638
TI  - What Is Your Diagnosis?

PMID- 30211639
TI  - In This Issue * October 1, 2018.

PMID- 30211641
TI  - Letters to the Editor.

PMID- 30211640
TI  - Investigation of potential risk factors for mesenteric volvulus in military
      working dogs.
AB  - OBJECTIVE To identify risk factors for mesenteric volvulus (MV) in military
      working dogs (MWDs). DESIGN Retrospective case-control study. ANIMALS 211 MWDs
      (54 with and 157 without MV [case and control dogs, respectively]). PROCEDURES
      Medical records (cases and controls) and necropsy reports (cases) were reviewed.
      Signalment, pertinent medical and surgical history, behavior and temperament
      characteristics, feeding schedules, and training types were recorded. Weather
      patterns for regions where dogs resided were researched. Data were evaluated
      statistically to identify potential risk factors for MV. RESULTS Risk factors
      significantly associated with MV included German Shepherd Dog breed (OR, 11.5),
      increasing age (OR, 2.0), and history of prophylactic gastropexy (OR, 65.9),
      other abdominal surgery (after gastropexy and requiring a separate anesthetic
      episode; OR, 16.9), and gastrointestinal disease (OR, 5.4). Post hoc analysis of
      the subset of MWDs that underwent gastropexy suggested that postoperative
      complications were associated with MV in these dogs but type of gastropexy and
      surgeon experience level were not. CONCLUSIONS AND CLINICAL RELEVANCE Data
      supported earlier findings that German Shepherd Dog breed and history of
      gastrointestinal disease were risk factors for MV. The MWDs with a history of
      prophylactic gastropexy or other abdominal surgery were more likely to acquire MV
      than were those without such history. These findings warrant further study.
      Despite the association between prophylactic gastropexy and MV, the authors
      remain supportive of this procedure to help prevent the more common disease of
      gastric dilatation-volvulus.

PMID- 30211642
TI  - Pathology in Practice.

PMID- 30211643
TI  - Minimally invasive, compartmentalized, modified open castration technique with
      primary closure in equids.
AB  - OBJECTIVE To describe use of a modified open castration technique with a scrotal
      approach and primary closure in equids. DESIGN Prospective case series. ANIMALS
      38 client-owned, sexually intact male equids. PROCEDURES With owner consent,
      elective castration was performed with a modified open technique on patients (1
      pony, 1 miniature horse, and 36 horses of other breeds) under general anesthesia.
      The procedure included minimal dissection into the scrotal region for removal of
      testes, with cremaster muscles left intact and the parietal vaginal tunic closed
      in place. Primary closure of surgical wounds was performed. Patients were
      monitored for signs of complications. Signalment, surgery-related variables,
      results of ultrasonographic imaging, postoperative treatments, and outcomes were
      recorded. Follow-up information was obtained from owners >= 6 months after
      surgery. Medical records were reviewed, and descriptive data were reported.
      RESULTS Median anesthesia and surgery times were 113.5 and 60 minutes,
      respectively. Duration of hospitalization ranged from 1 to 3 days. No
      intraoperative complications were observed. Postoperative complications (moderate
      swelling in the scrotal region) developed in 2 of 38 (5%) patients. Mild scrotal
      swelling (n = 5) and transient pyrexia (typically mild; 9) also occurred; no
      patients had signs of postoperative bleeding, infection, or colic. All equids
      gradually returned to exercise beginning 10 days after the procedure. Cosmetic
      results were considered excellent. CONCLUSIONS AND CLINICAL RELEVANCE The
      modified castration technique was considered simple to perform and advantageous
      because of the low complication rate, excellent cosmetic results, and prompt
      return to intended use after surgery.

PMID- 30211644
TI  - Incidence of chyloabdomen diagnosis in dogs and cats and corresponding clinical
      signs, clinicopathologic test results, and outcomes: 53 cases (1984-2014).
AB  - OBJECTIVE To determine the incidence of chyloabdomen diagnosis in cats and dogs
      and characterize and compare between species the corresponding clinical signs,
      clinicopathologic test results, and outcomes. DESIGN Retrospective case series.
      ANIMALS 36 cats and 17 dogs in which chyloabdomen was diagnosed at a veterinary
      teaching hospital between 1984 and 2014. PROCEDURES Medical records were
      reviewed, and data retrieved included patient signalment; clinical signs at
      initial evaluation; results of physical examination, diagnostic tests, and
      imaging studies; and outcomes. Survival analyses, descriptive statistics, and
      comparisons between species were completed. RESULTS The incidence of chyloabdomen
      at the veterinary teaching hospital during the study period was 2.0 cases/100,000
      admissions for cats and 2.8 cases/100,000 admissions for dogs. The mean age at
      diagnosis of chyloabdomen in cats was 11.3 years, compared with 6.9 years in
      dogs. The most common clinical signs in dogs and cats combined were lethargy
      (39/51 [76%]) and anorexia (37/51 [73%]), but fewer (23/53 [43%]) had abdominal
      distention. Chylothorax was a common comorbidity (25/53 [47%]), with malignant
      neoplasia being the most common underlying diagnosis (24/53 [45%]). Survival
      analyses included 44 patients; median survival time from diagnosis of
      chyloabdomen was 31 days overall, 8 days for patients with malignant neoplasia,
      and 73 days for patients without neoplasia. CONCLUSIONS AND CLINICAL RELEVANCE
      There were multiple causes of chyloabdomen in dogs and cats of the study, and
      outcome depended on underlying cause. Because of this and the rarity of
      chyloabdomen, a multicenter prospective study of disease progression, treatment
      response, and clinical outcome for dogs and cats with chyloabdomen is needed.

PMID- 30211645
TI  - Gastric dilatation and enterotoxemia in ten captive felids.
AB  - CASE DESCRIPTION 10 large felids at 8 facilities were determined or suspected to
      have developed gastric dilatation with or without enterotoxemia over a 20-year
      period. Four felids were found dead with no premonitory signs. CLINICAL FINDINGS
      4 felids (2 male snow leopards [Uncia uncia], 1 male Amur tiger [Panthera tigris
      altaica], and 1 male Sumatran tiger [Panthera tigris sumatrae]) were found dead
      or died before they could be evaluated. Six felids had hematemesis (1 male and 1
      female African lion [Panthera leo] and 1 male jaguar [Panthera onca]) or
      abdominal distention and signs of lethargy with or without vomiting (1 male
      African lion, 1 male Malayan tiger [Panthera tigris jacksoni], and 1 female
      Sumatran tiger). Gastric dilatation was radiographically and surgically confirmed
      in the male Malayan and female Sumatran tigers and the jaguar. TREATMENT AND
      OUTCOME In 3 felids with an antemortem diagnosis, the gastric dilatation resolved
      with decompressive laparotomy but then recurred in 1 felid, which subsequently
      died. Three others died at various points during hospitalization. Although
      Clostridium perfringens type A was recovered from 3 of the 5 felids for which
      microbial culture was performed, and 2 felids had a recent increase in the amount
      fed, no single factor was definitively identified that might have incited or
      contributed to the gastric dilatation. CLINICAL RELEVANCE Gastric dilatation was
      a life-threatening condition in the large felids of this report, causing sudden
      death or clinical signs of hematemesis, abdominal distention, or vomiting. Even
      with rapid diagnosis and surgical decompression, the prognosis was poor. Research
      is needed into the factors that contribute to this emergent condition in large
      felids so that preventive measures might be taken.

PMID- 30211646
TI  - Factors associated with strongyle infection in goats at the individual and farm
      level.
AB  - OBJECTIVE To identify factors associated with strongyle infection and parasite
      reduction strategies associated with low strongyle fecal egg counts (FECs) in
      goats on farms in North Carolina. DESIGN Cross-sectional study. ANIMALS 631 adult
      goats on 52 farms in North Carolina. PROCEDURES Participating farms were visited
      to collect fecal samples from goats and administer a survey regarding goat,
      environmental, and management factors. The McMaster technique was used to
      determine strongyle FEC for each sample. Univariate followed by multivariate
      modeling was performed to identify factors associated with FEC at the farm and
      individual goat level. RESULTS Multivariate analysis controlling for several
      other factors and multiple comparisons revealed that farms on which no
      anthelmintic drugs had ever been used had the lowest mean FECs, compared with
      farms on which specific strategies for parasite control were used; no other
      variables were significant. For individual goat FEC, significant variables
      included goat breed, breed type, owner-defined purpose, daily dietary protein
      intake, and fecal coccidia score. In particular, companion goats (vs meat or
      dairy goats) had the lowest FECs. Higher dietary protein intake and coccidia
      scores were associated with higher FECs. Among females, goats that had kidded in
      the last 6 weeks had the highest FECs. CONCLUSIONS AND CLINICAL RELEVANCE Various
      factors were identified that appeared to influence the likelihood of strongyle
      infection in goats. The finding that farms with no history of anthelmintic use
      had the lowest mean FECs suggested that a focus on preventative measures could
      reduce the need for anthelmintic drugs and, by extension, lessen the opportunity
      for the development of anthelmintic resistance.

PMID- 30211648
TI  - Pathology in Practice.

PMID- 30211649
TI  - Diagnostic and therapeutic challenges for dogs with urinary tract infections
      caused by extended-spectrum beta-lactamase-producing Escherichia coli.

PMID- 30211650
TI  - Resolution of hyperinsulinemic hypoglycemia following partial pancreatectomy in a
      dog with nesidioblastosis.
AB  - CASE DESCRIPTION A 6-year-old castrated male Australian Shepherd was evaluated
      because of a recent onset of persistent hypoglycemia. CLINICAL FINDINGS Physical
      examination results were generally unremarkable. No abnormalities were detected
      on thoracic radiographs, and abdominal ultrasonography revealed no obvious
      pancreatic lesion. Hematologic analysis revealed hypoglycemia with a high serum
      insulin-to-glucose concentration ratio. TREATMENT AND OUTCOME Insulinoma was
      suspected; medical treatment with prednisone was initiated, and exploratory
      laparotomy was performed. No pancreatic lesions or masses were observed. Partial
      left pancreatectomy and hepatic and local lymph node biopsies were performed.
      Histologic examination revealed islet cell hypertrophy and hyperplasia, with no
      evidence of neoplasia. Results of a PCR assay of the pancreatic tissue for
      Bartonella infection were negative. Clinical, biochemical, and histopathologic
      findings were compatible with nesidioblastosis. The clinical signs, including
      hypoglycemia, resolved after surgery. On follow-up examination 8 months later,
      the dog was apparently healthy and results of a CBC and serum biochemical
      analysis, including blood glucose concentration, were within respective reference
      ranges. CLINICAL RELEVANCE To our knowledge, this is the first report of
      nesidioblastosis in a dog for which clinical signs and clinicopathologic
      abnormalities resolved after partial pancreatectomy. Although extremely rare,
      nesidioblastosis should be considered a differential diagnosis in dogs with signs
      suggestive of insulinoma.

PMID- 30211651
TI  - PDGFBB promotes proliferation and migration via regulating miR-1181/STAT3 axis in
      human pulmonary arterial smooth muscle cells.
AB  - Platelet-Derived Growth Factor (PDGF) can induce hyperproliferation of Pulmonary
      Artery Smooth Muscle Cells (PASMCs), which is a key causative factor to the
      occurrence and progression of pulmonary arterial hypertension (PAH). We
      previously identified that miR-1181 is significantly downregulated by PDGFBB in
      human PASMCs. In this work, we further explore the function of miR-1181 and
      underlying regulatory mechanisms in PDGF-induced PASMCs. First, the expression
      pattern of miR-1181 was characterized under PDGFBB treatment, and PDGFR/PKCbeta
      signaling was find to repress miR-1181 expression. Then, gain- and loss-of
      function experiments were respectively conducted and revealed the prominent role
      of miR-1181 in inhibiting PASMCs proliferation and migration. Flow cytometry
      analysis suggested that miR-1181 regulated the PASMCs proliferation through
      influencing the cell cycle transition from G0/G1 to S phase. Moreover, we
      exhibited that miR-1181 targeting STAT3 formed a regulatory axis to modulate
      PASMCs proliferation. Finally, serum miR-1181 expression was also observed to be
      reduced in adult and newborn PAH patients. Overall, this study provides novel
      findings that miR-1181/STAT3 axis mediated PDGFBB-induced dysfunction in human
      PASMCs, implying a potential use of miR-1181 as a therapeutic and diagnostic
      candidate for the vascular remodeling diseases.

PMID- 30211652
TI  - Buffer drains and mucus is transported upward in a tilted mucus clearance assay.
AB  - Mucociliary clearance (MCC) plays an essential role in maintaining airway
      sterility and health. Conversely, mucociliary dysfunction is implicated across
      many airway obstructive diseases. Understanding the necessary requirements for
      successful MCC is imperative to establish the pathology of disease as well as to
      develop therapeutic strategies. Although gravitational drainage is used
      clinically via postural drainage to aid mucus clearance, it is ignored in both
      animal and cell culture models of MCC. In this study we develop a novel mucus
      clearance assay that enables the first particle image velocimetry of human
      bronchial epithelial cell cultures tilted relative to the gravitational field.
      This tilting system makes it possible to observe drainage of the airway surface
      liquid, and thus the effect that gravity has on mucociliary clearance. First we
      use this assay to demonstrate that buffer alone cannot be transported upward
      against gravity by beating cilia. Next we show that, over the same region of
      ciliated epithelia cells, mucus can be transported upward by beating cilia. These
      results indicate that the biophysical and biochemical properties of mucus enable
      vertical clearance and that current assay systems aren't equipped to determine
      which properties are required for physiologically relevant vertical mucociliary
      clearance.

PMID- 30211653
TI  - Generation of an alveolar epithelial type II cell line from induced pluripotent
      stem cells.
AB  - Differentiation of primary alveolar type II epithelial cells (AEC type II) to AEC
      type I in culture is a major barrier in the study of the alveolar epithelium in
      vitro. The establishment of an AEC type II cell line derived from induced
      pluripotent stem cells (iPSC) represents a novel opportunity to study alveolar
      epithelial cell biology, for instance in the context of lung injury, fibrosis and
      repair. In the present study, we generated long lasting AECII from iPSC (iPSC
      AEC). Long lasting iPSC-AECII (LL)-iPSC-AECII) displayed morphological
      characteristics of AECII including growth in a cobble stone monolayer, the
      presence of lamellar bodies and microvilli as shown by electron microscopy. Also,
      (LL)-iPSC-AECII expressed AEC type II proteins such as cytokeratin, surfactant
      protein C and lysotracker DND 26 (a marker for lamellar bodies). Furthermore, the
      (LL)-iPSC-AECII exhibited functional properties of AECII by an increase of
      transepithelial electrical resistance (TERR) over time, secretion of inflammatory
      mediators in biologically relevant quantities (interleukin-6, interleukin-8) and
      efficient in vitro alveolar epithelial wound repair. Consistent with the AECII
      phenotype, the cell line showed the ability to uptake and release surfactant
      protein B, to secrete phospholipids and to differentiate into AEC type I. In
      summary, we established a long lasting, but finite AEC type II cell line derived
      from iPSC as a novel cellular model to study alveolar epithelial cell biology in
      lung health and disease.

PMID- 30211654
TI  - Oxidative stress associated with aging activates Protein Kinase C Epsilon,
      leading to cilia slowing.
AB  - Older people are four times more likely to develop pneumonia than younger people.
      As we age, many components of pulmonary innate immunity are impaired, including
      slowing of mucociliary clearance. Ciliary beat frequency (CBF) is a major
      determinant of mucociliary clearance, and it slows as we age. We hypothesized
      that CBF is slowed in aging due to increased oxidative stress, which activates
      PKCepsilon signaling. We pharmacologically inhibited PKCepsilon in ex vivo mouse
      models of aging. We measured a slowing of CBF with aging that was reversed with
      inhibition using the novel PKC inhibitor, Ro-31-8220, as well as the PKCepsilon
      inhibitor, PKCe141. Inhibition of PKCepsilon using siRNA in mouse trachea also
      returned CBF to normal. In addition, antioxidants decrease PKCepsilon activity
      and speed cilia. We also aged wild type and PKCepsilon KO mice and measured CBF.
      The PKCepsilon KO mice were spared from the CBF slowing of aging. Using human
      airway epithelial cells from younger and older donors at air-liquid interface
      (ALI), and used siRNA to inhibit PKCepsilon. We measured a slowing of CBF with
      aging that was reversed with siRNA inhibition of PKCepsilon. In addition, we
      measured bead clearance speeds in human ALI, which demonstrated a decrease in
      bead velocity with aging and a return to baseline after inhibition of PKCepsilon.
      In summary, in human and mouse models, aging is associated with increased oxidant
      stress, which activates PKCepsilon and slows CBF.

PMID- 30211656
TI  - Don't Get Too Excited: Assessing Individual Differences in the Down-Regulation of
      Positive Emotions.

PMID- 30211655
TI  - Former Preterm Lambs have Persistent Alveolar Simplification at 2 and 5 Months
      Corrected Postnatal Age.
AB  - Preterm birth and mechanical ventilation (MV) frequently lead to bronchopulmonary
      dysplasia, the histopathological hallmark of which is alveolar simplification.
      How developmental immaturity and ongoing injury, repair, and remodeling impact
      completion of alveolar formation later in life is not known, in part because of
      lack of suitable animal models. We report a new model using former preterm lambs
      to test the hypothesis that they will have persistent alveolar simplification
      later in life. Moderately preterm lambs (~85% gestation) were supported by MV for
      ~6 days before being transitioned from all respiratory support to become former
      preterm lambs. Results are compared to term control lambs that were not
      ventilated, and between males (M) and females (F). Alveolar simplification was
      quantified morphometrically and stereologically at 2 months (4M:4F) or 5 months
      (4M:6F) corrected postnatal age (cPNA) compared to unventilated, age-matched term
      control lambs (4M:4F per control group). These postnatal ages in sheep are
      equivalent to human postnatal ages of 1-2 years and ~6 years, respectively.
      Multivariable linear regression results showed that former preterm lambs at 2 or
      5 months cPNA had significantly thicker distal airspace walls (p<0.001 and
      p<0.009, respectively), lower volume density of secondary septa (p<0.007 and
      p<0.001, respectively), and lower radial alveolar count (p<0.003 and p<0.020,
      respectively) compared to term control lambs. Sex-specific differences were not
      detected. We conclude that moderate preterm birth and MV for ~6 days impedes
      completion of alveolarization in former preterm lambs. This new model provides
      opportunity to identify underlying pathogenic mechanisms that may reveal
      treatment approaches.

PMID- 30211657
TI  - Detection of Two Peronospora spp., Responsible for Downy Mildew, in Opium Poppy
      Seed.
AB  - Downy mildew is a serious threat to opium poppy production globally. In recent
      years, two pathogen species, Peronospora somniferi and Peronospora meconopsidis,
      which induce distinct symptoms, have been confirmed in Australia. In order to
      manage the spread of these pathogens, identifying the sources of inoculum is
      essential. In this study, we assessed pathogen presence associated with poppy
      seed. We developed PCR and qPCR assays targeting the coxI and coxII gene regions,
      for the detection, differentiation, and quantification of P. somniferi and P.
      meconopsidis in poppy seed. These results were complemented and compared with
      direct seed histological examination and a seed washing combined with viability
      staining for oospore detection. The majority of seed lots from all harvest years
      contained detectable P. meconopsidis, the earliest (1987) predating the first
      official record of the disease in Tasmania (1996). In contrast, only seed lots
      harvested in 2012 or later contained P. somniferi, evidence of its more recent
      introduction. P. meconopsidis contamination was estimated to be as high as 33.04
      pg DNA/g of seed and P. somniferi as high as 35.17 pg DNA/g of seed. Incidence of
      pathogen contamination of seeds, estimated via a group testing protocol, ranged
      from 0 to 9% (P. meconopsidis) or 0 to 11% (P. somniferi). Mycelia were
      predominately found external to the seed coat. Seed washing and viability
      staining demonstrated that putatively viable oospores were present in the
      majority of seed lots. Transmission testing confirmed both pathogens can be
      successfully transmitted from infested seed to infected seedling. PCR and qPCR
      pathogen assays were found to be reliable and offer a routine test for
      determining pathogen inoculum in poppy seeds.

PMID- 30211658
TI  - Comparison of Whole Plant and Detached Leaf Screening Techniques for Identifying
      Anthracnose Resistance in Strawberry Plants.
AB  - Anthracnose is a destructive disease of strawberry caused by several
      Colletotrichum species including C. acutatum, C. fragariae, and C.
      gloeosporioides. Identification of anthracnose resistant strawberry germplasm has
      commonly relied on inoculation of whole plants with isolates of these pathogens.
      In this study, whole plants and detached leaves from 81 germplasm lines were
      inoculated with a conidial suspension of isolates of C. acutatum, C. fragariae,
      and C. gloeosporioides, incubated in the dark at 30 degrees C, 100% relative
      humidity, for 48 h, and assessed for disease severity based on symptoms on
      inoculated petioles and leaves. The correlation between the disease severity
      ratings of the whole plants rated 30 days after inoculation and detached leaves
      rated 5 days after inoculation was determined. Based on leaf symptoms and petiole
      lesions, the association between the whole plant leaf disease severity rating
      (DSR) and detached leaf DSR was positive (rp = 0.70), and the association between
      the whole plant DSR and the detached leaf DSR was also positive (rp = 0.66).
      Whole plant and detached leaf DSRs were used to assign each germplasm line to a
      resistance category, and a posthoc Tukey's test showed that the whole plant DSR
      means and the detached leaf DSR means for each resistance category differed
      significantly at p < 0.05. This research was used to develop a strawberry
      detached leaf assay which can reliably and quickly determine the degree of
      resistance of strawberry germplasm to anthracnose.

PMID- 30211659
TI  - The lipid environment determines the activity of the Escherichia coli ammonium
      transporter AmtB.
AB  - The movement of ammonium across biologic membranes is a fundamental process in
      all living organisms and is mediated by the ubiquitous ammonium
      transporter/methylammonium permease/rhesus protein (Amt/Mep/Rh) family of
      transporters. Recent structural analysis and coupled mass spectrometry studies
      have shown that the Escherichia coli ammonium transporter AmtB specifically binds
      1-palmitoyl-2-oleoyl phosphatidylglycerol (POPG). Upon POPG binding, several
      residues of AmtB undergo a small conformational change, which stabilizes the
      protein against unfolding. However, no studies have so far been conducted, to our
      knowledge, to explore whether POPG binding to AmtB has functional consequences.
      Here, we used an in vitro experimental assay with purified components, together
      with molecular dynamics simulations, to characterize the relation between POPG
      binding and AmtB activity. We show that the AmtB activity is electrogenic. Our
      results indicate that the activity, at the molecular level, of Amt in
      archaebacteria and eubacteria may differ. We also show that POPG is an important
      cofactor for AmtB activity and that, in the absence of POPG, AmtB cannot complete
      the full translocation cycle. Furthermore, our simulations reveal previously
      undiscovered POPG binding sites on the intracellular side of the lipid bilayer
      between the AmtB subunits. Possible molecular mechanisms explaining the
      functional role of POPG are discussed.-Mirandela, G. D., Tamburrino, G.,
      Hoskisson, P. A., Zachariae, U., Javelle, A. The lipid environment determines the
      activity of the Escherichia coli ammonium transporter AmtB.

PMID- 30211660
TI  - Mesencephalic astrocyte-derived neurotrophic factor affords neuroprotection to
      early brain injury induced by subarachnoid hemorrhage via activating Akt
      dependent prosurvival pathway and defending blood-brain barrier integrity.
AB  - This study aimed to explore the neuroprotective effect of mesencephalic astrocyte
      derived neurotrophic factor (MANF) protein on early brain injury caused by
      subarachnoid hemorrhage (SAH) and the relevant mechanisms in experimental rats,
      expecting to understand whether MANF was a potential therapeutic target for SAH
      treatment. A perforation model of SAH was introduced into the study. Recombinant
      human MANF (rh-MANF) and protein kinase B (Akt) inhibitor (MK2206) were used to
      explore the effect and the mechanisms. Multiple approaches for systemic
      assessment were employed in the research, including the Garcia test, the SAH
      grade, Evans blue (EB) dye leakage, brain-water content (BWC), the rotarod test,
      and the Morris water-navigation task, as were biotechniques, such as
      immunohistochemistry, Western blot, transmission electron microscopy, and flow
      cytometry. MANF was mainly expressed in rat neurons, and its expression increased
      significantly at 3 h after SAH induction and peaked at 24 h. Stereotactic
      injection of rh-MANF into the cerebroventricle significantly increased the level
      of MANF, p-Akt, p-mouse double minute 2 homolog (p-MDM2), and B-cell lymphoma 2
      (Bcl-2) in brain tissue, whereas it down-regulated the expression of P53, Bcl-2
      associated X protein (Bax), and cleaved caspase-3, which indicated that neuronal
      apoptosis was remarkably suppressed. Expression of matrix metallopeptidase 9 (MMP
      9) was also suppressed by the rh-MANF injection. Furthermore, neurologic
      deficits, EB dye leakage, and BWC were reduced, and long-lasting neuroprotection
      was noted with rh-MANF administration. The antiapoptotic and blood-brain barrier
      (BBB) protective effect could be offset by administering MK2206. MANF could
      alleviate neuronal apoptosis by activating Akt-dependent prosurvival pathway and
      abate BBB damage via MMP-9 suppression. MANF showed not only transient but also
      long-lasting neuroprotective properties. The rh-MANF as a potential drug for
      treating SAH might be of clinical use.-Li, T., Xu, W., Gao, L., Guan, G., Zhang,
      Z., He, P., Xu, H., Fan, L., Yan, F., Chen, G. Mesencephalic astrocyte-derived
      neurotrophic factor affords neuroprotection to early brain injury induced by
      subarachnoid hemorrhage via activating Akt-dependent prosurvival pathway and
      defending blood-brain barrier integrity.

PMID- 30211661
TI  - Dispositional Perspective-Taking and Empathic Concern Modulate the Impact of
      Cognitive Load on Empathy for Facial Emotions.
AB  - Meeting other people involves the importance to share their experiences and to
      understand their perspectives or, more simply, to empathize with them. Empathy
      research distinguishes two main dimensions of empathy, the affective sharing and
      the cognitive understanding. In the present study, we focus on the impact of
      cognitive load on empathy to pain, fear, happiness, and neutral facial emotions.
      Participants had to judge the intensity of the emotion when looking to facial
      expressions (empathize group), or with an additional eight-digit memory task
      (cognitive load group). While we assumed that cognitive load would reduce
      empathy, inconsistently with previous findings, our results did not show any
      significant effect of group. Interestingly, regression analyses showed that
      perspective-taking and empathic concern were positively related to pain, fear,
      and happiness ratings within the cognitive load group. These results reveal that
      when judging empathy under high cognitive load, dispositional empathic concern
      and perspective-taking could allow individuals to override the supposed
      deleterious cognitive load effect on empathy.

PMID- 30211662
TI  - Protective Effect of Chickpea Protein Hydrolysates on Colon Carcinogenesis
      Associated With a Hypercaloric Diet.
AB  - OBJECTIVE: Colon cancer occupies the third place in incidence worldwide; eating
      habits, in particular, consumption of hypercaloric diets, are relevant in its
      etiopathogenesis. On the other hand, foods can also modulate carcinogenesis: for
      example, proteins, which when hydrolyzed release peptides with biological
      activities, and legumes, especially, chickpea, represent a good source of
      hydrolysates. The objective of this work was to verify the inhibitory effect of
      chickpea hydrolyzed protein on azoxymethane (AOM)-induced carcinogenesis in mice
      fed a hypercaloric diet. METHODS: We hydrolyzed chickpea protein by pepsin,
      pancreatin, and a combined pepsin-pancreatin system, to test its anticarcinogenic
      and hypercaloric activity in mice that had consumed a hypercaloric diet or a
      normal diet but were injected with azoxymethane (AOM). RESULTS: A concentrate
      (70% proteins) was obtained from chickpea seeds (18.5% proteins), and extensive
      hydrolysates were obtained at 15 minutes, in all tested enzyme systems. The
      greatest activity was evidenced in the hydrolysates obtained with pepsin
      pancreatin at 90 minutes. Animals that consumed the hypercaloric diet had a
      higher concentration of cholesterol and a higher atherogenic index, which were
      significantly reduced with the administration of chickpea protein hydrolysates
      with a dose-response effect (10, 20, or 30 mg/kg), whereas no effect was observed
      in animals that consumed the normal diet. In animals given AOM, aberrant crypts
      were observed, at a higher rate in animals that consumed the hypercaloric diet;
      with the consumption of hydrolysates by the animals that consumed either diet,
      the number of aberrant crypts was reduced with the 3 doses tested, and the effect
      was better in those animals fed the hypercaloric diet. The best effect in all
      tests was with 30 mg/kg body weight. CONCLUSION: The consumption of chickpea
      protein hydrolysates might confer a protective effect against colon
      carcinogenesis.

PMID- 30211663
TI  - Fast and simple determination of moroxydine residues in pig and chicken samples
      by ultra-performance liquid chromatography-tandem mass spectrometry.
AB  - A general solid-phase extraction (SPE) method using ultra-performance liquid
      chromatography-tandem mass spectrometry (UPLC-MS/MS) for the determination of
      moroxydine residues in pig and chicken samples has been developed. After
      extraction and purification of real samples, moroxydine residues were detected
      using a hydrophobic interaction liquid chromatography column with an optimised
      mobile phase composition. The extraction reagents, the kind of SPE columns and
      the type of eluents were optimised to achieve the maximum extraction efficiency.
      The matrix effects from the animal tissue influenced the quality of the
      quantitative data obtained. Under the optimised conditions, the moroxydine
      residues in pig and chicken samples spiked at three levels (1.0 MUg/kg, 5.0
      MUg/kg and 10.0 MUg/kg) were determined with good recoveries (61.5%-105.4%) and
      adequate relative standard deviations (3.2%-13.0%). In pig and chicken samples,
      the limit of detection (LOD) was 0.3 MUg/kg, and the limit of quantification
      (LOQ) was 1.0 MUg/kg. A sufficiently linear relationship in the range of 1.0
      MUg/kg-20.0 MUg/kg was achieved with a good correlation coefficient (R2 >= 0.99).

PMID- 30211664
TI  - Contributors to Women's Perceived Stress at the Start of Assisted Reproductive
      Technology.
AB  - Clinicians are often called upon to treat the stress that accompanies Assisted
      Reproductive Technology (ART). In this study, we sought to examine the
      contribution of the internal resources of meaning in life and attachment style
      and the interpersonal resource of self-disclosure to her mother to a woman's
      level of perceived stress upon commencement of ART. In addition, we examined the
      association between age and perceived stress. The sample consisted of 180 Israeli
      women (106 aged 20-34; 74 aged 35-44) who completed a series of self-report
      questionnaires after their initial meeting with a fertility specialist.
      Regression analysis indicated that older age, lower attachment anxiety, higher
      perception of meaning in life, and greater self-disclosure to the mother were
      related to lower levels of perceived stress. Self-disclosure was also found to
      mediate the association between avoidant attachment and stress. The study
      highlights the importance of a woman's personal and interpersonal resources for
      reducing the experience of stress in the early stages of ART. The results have
      practical implications for the development of professional interventions seeking
      to enhance these resources among women embarking on fertility treatment.

PMID- 30211665
TI  - Traumatic Brain Injury and Sexually Offensive Behaviors.
AB  - Sexually offensive behavior is known to be one of many consequences of traumatic
      brain injury (TBI). This article provides a brief review of research to ascertain
      the effects of TBI in childhood and adulthood as related to cognitive,
      behavioral, social, and sexual behaviors. Brain impairment is also identified as
      a result of adverse childhood experiences (ACEs). Individuals with sexual
      offending histories are found to have experienced high numbers of ACEs. Sexually
      offensive and sexual offending behaviors post-TBI appears to occur in between 3.5
      and 9% of affected adults (Simpson, Blaszczynski & Hodgkinson, 1999; Simpson,
      Sabaz & Daher, 2013). It is recommended that treatment providers make themselves
      aware of the relationship between TBI, ACEs, and sexually offensive behavior and
      how this may affect the treatment process.

PMID- 30211666
TI  - Abstractness and Messages Describing Consequences Promote Healthier Behavioral
      Intentions.
AB  - Many health-risk behaviors present a self-control conflict in which the short
      term outcomes of an action conflict with its long-term consequences. Across three
      studies, we find that an abstract construal level leads people to focus on long
      term rather than short-term consequences when both are described in a message
      (vs. no message). Studies 1 and 2 explore this hypothesis through a risk behavior
      (snacking on sugary products), and Study 3 does the same through a health
      behavior (physical exercise). In Study 1, the Behavioral Identification Form
      scale is used to measure the construal level as a personal disposition; Studies 2
      and 3 use a priming task designed by Freitas, Gollwitzer, and Trope to manipulate
      the construal level. All these studies show that, under an abstract mindset,
      people who have read a mixed-outcome message (vs. no message) tend to base their
      behavioral plans on long-term outcomes. Individually or in small groups (e.g.
      school class, therapy groups) health messages can be presented along with
      protocols to change construal level and thus, promote healthier intentions.

PMID- 30211667
TI  - The new social work.
AB  - Social work practice is an industry based mostly on therapist intuition and gut
      feelings. There are virtually no real-time, reliable data showing the performance
      of any patient outcomes or on therapists providing treatment services. In this
      paper a new system is recommended, performance-based practice. In the future, the
      New Social Work proposed will not operate as a system in which patients enter
      community facilities to sit in waiting rooms and interact with a randomly
      assigned therapist for one hour a few times weekly. Social service building will
      transform into technology centers where therapists use tools to measure and
      intervene with patients in real-time. The New Social Work will finally understand
      that people do not recover or learn how to recover in therapist's offices-but in
      their own communities-with assistance from high-performance professional
      therapists interacting in the moment.

PMID- 30211668
TI  - Nerve root entrapment with pseudomeningocele after percutaneous endoscopic lumbar
      discectomy: A case report.
AB  - CONTEXT: Pseudomeningocele is a relatively uncommon postoperative complication of
      spine surgery. Although the condition tends to be asymptomatic and self-limiting,
      it may cause radicular pain and neurological defect due to herniation of the
      nerve root or the spinal cord. Its pathophysiology remains unclear. Only few
      cases with intraoperative photos have been reported. FINDING: We present a case
      of pseudomeningocele with nerve root entrapment after percutaneous endoscopic
      lumbar discectomy (PELD). A 52-year-old man had undergone PELD for sciatic pain
      and showed good postoperative recovery. Unfortunately, he was readmitted for
      progressive right leg pain at six weeks after the surgery. After the failure of
      conservative therapy, he received PELD again to explore the surgical site.
      Intraoperatively, a pseudomeningocele-containing nerve root, herniating through a
      small defect in the dural sac, was identified. During the dissection process, the
      pseudomeningocele was broken, which led to entrapment of the nerve root.
      Thereafter, the microsurgical technique was adopted to relocate the nerve root
      into the thecae sac and to repair the dural tear by non-resorbable suture.
      CONCLUSION: To our knowledge, this case report is the first documented instance
      of identification of a pseudomeningocele under an endoscope, and provides
      insights into the transformation of a pseudomeningocele into a cerebrospinal
      fluid fistula with nerve root entrapment. For neurological deficit caused by
      pseudomeningocele following PELD, operative revision by the microsurgery
      technique is the appropriate strategy.

PMID- 30211670
TI  - Operational strategy of high rate anaerobic digester with mixed organic wastes:
      effect of co-digestion on biogas yield at full scale.
AB  - The present research work is aimed at providing an economically feasible solution
      for the farmers to exploit the mixed organic wastes (MOW) as resources for the
      generation of biogas based electrical power and utilize the same for irrigation
      purpose to reduce the dependence on electricity board. A full scale
      biomethanation plant has been installed based on anaerobic gas lift reactor (AGR)
      technology to analyse, understand the operational parameters of anaerobic
      digestion and assess the performance of a high rate biomethanation plant by co
      digesting the MOW such as poultry litter (PL), cattle manure (CM) and napier
      grass (NG) at ambient temperature. The biomethanation plant was incorporated with
      inline pre and post-processing unit assembly. The plant was fed with 1000 kg of
      MOW per day having 250 kg of total solids, about 178-200 kg of volatile solids
      and operated continuously for 52 weeks under ambient temperature. Electrical
      power generated (84.5-104 kWh/day) from biogas (65-80 m3/day) containing methane
      (40-48 m3/day) was used for operating the water pumps for agricultural purpose
      and the digestate (115-130 kg/day) was exploited as organic manure for growing
      crops in the same field. Napier grass was grown in the same land and other
      feedstocks were procured from the nearby area at the cost of $10-$15 per ton.
      Around 6 acres of land was being cultivated using the biogas based power
      generated from the MOW that was being used for growing vegetables and maize.

PMID- 30211669
TI  - Role of variants rs5030717 and rs5030718 of TLR4 in the risk prediction of
      nephropathy, hypertension and dyslipidaemia in type 2 diabetes mellitus.
AB  - BACKGROUND: Type 2 diabetes mellitus describes a metabolic disorder characterised
      by prolonged elevated blood glucose that brings a risk of developing
      microvascular and macrovascular disease. Several factors, such as dysregulation
      of the Toll-like receptor 4 (TLR-4), are reputed to contribute to the multiple
      pathophysiological disturbances responsible for impaired glucose homeostasis. We
      hypothesised that variants rs5030717 and rs5030718 of TLR4 are associated with
      diabetic nephropathy, hypertension and dyslipidaemia. MATERIAL & METHODS: We
      recruited 370 diabetics (122 with nephropathy, 119 with hypertension and 129 with
      dyslipidaemia) and 120 ethnicity matched healthy controls. TLR4 polymorphisms
      were evaluated using polymerase chain reaction followed by restriction fragment
      length polymorphism analysis. The genotyping data were compared between cases and
      controls using chi-square test and logistic regression analysis. RESULTS:
      Although there was no overall difference in the genotype frequencies of TLR4
      rs5030717 in diabetes v controls, the genotype frequencies of diabetic
      dyslipidaemia cases compared with controls were different (p = 0.001). Overall,
      the rs5030718 GA and GG genotype frequencies in the entire diabetes cohort were
      different from those of the controls (p = 0.037), and the frequencies of diabetic
      nephropathy cases (p = 0.03) and diabetic dyslipidaemia cases were different (p =
      0.001) compared with controls. There were no links with diabetic hypertension.
      CONCLUSION: TLR4 polymorphisms rs5030717 and rs5030718 may be useful in
      predicting those type 2 diabetics who are at risk of hypertension, nephropathy
      and/or dyslipidaemia.

PMID- 30211671
TI  - Recruitment, enrollment & data collection with victims of elder abuse and neglect
      identified from police incident reports.
AB  - This study evaluated the success of researcher-generated recruitment, enrollment,
      data collection, and safety protocols for field research with victims of elder
      abuse and neglect (EAN) identified from police incident reports in terms of their
      success including cost-effectiveness, ability to generate a representative
      sample, and safety. After reviewing 492 police incident reports involving victims
      age 65 years or older to identify cases of EAN 62 victims were identified. Mail,
      phone, and in-person recruitment strategies were used. After 259 recruitment
      attempts, 52 (84%) eligible victims were contacted, of which 24 (46%) consented
      to participate. Phone calls were the least expensive mechanism to produce a
      successfully enrolled participant. Findings from a regression show completion of
      a research interview could not be predicted by victim, suspect, or offense
      characteristics, indicating that the recruited victims likely represent the
      population they were drawn from. No safety or adverse events occurred.

PMID- 30211672
TI  - Predictors and consequences of sudden gains in transdiagnostic cognitive
      behavioural therapy for anxiety disorders.
AB  - Sudden gains-substantial stable symptom improvements between consecutive therapy
      sessions-are a common phenomenon. As condensed points of change, examination of
      sudden gains can provide insight into mechanisms of therapeutic change. This
      study investigated the association between sudden gains and cognitive change,
      therapeutic alliance, and/or client engagement in transdiagnostic group cognitive
      behavioural therapy for anxiety disorders. Of 58 treatment initiators, 21% (n =
      12) exhibited a sudden gain. Consistent with previous research, sudden gainers
      demonstrated significantly greater pre- to post-treatment symptom improvement
      than non-sudden gainers. Observational coding of therapy sessions found that
      sudden gains were associated with elevated levels of cognitive change and client
      engagement in the pre-gain session, and elevated levels of cognitive change and
      therapeutic alliance in the post-gain session. However, these results varied by
      use of within- and between-subject control comparisons, highlighting the value
      using a dual control methodology. In context of previous research, the results on
      cognitive change replicate previous findings in depressive populations, and
      clarify mixed findings in anxiety populations. The results on therapeutic
      alliance replicate previous findings for the first time in an anxiety sample,
      although the between-subject control comparisons revealed complexity previously
      undetected. This study was also the first to investigate and thus establish the
      relation between client engagement and sudden gains.

PMID- 30211674
TI  - National Ethical Guidelines for Biomedical and Health Research Involving Human
      Participants, 2017: A commentary.
AB  - The Indian Council of Medical Research (ICMR) has been at the forefront in
      setting up the ethical guidance for the conduct of biomedical and health research
      in India. The latest version of National Guidelines for Biomedical and Health
      Research Involving Human Participants, 2017 was planned in order to provide a
      more detailed guidance to the existing topics in view of emerging ethical
      concerns and to add a number of newer areas in which guidance was lacking. The
      scope of the guidelines has been expanded to include socio-behavioural research
      related to health and research involving biological material and datasets. The
      guidelines have 12 sections which cover a wide range of topics and areas of
      research. The first six sections are more generic, applying to all types of
      biomedical and health research, while the next six sections are more subject
      specific. The guidelines have been revised in consultation with a large number of
      experts and stakeholders and went through an exhaustive process stretching over a
      period of two years in its drafting, review, consultation and finalisation. This
      commentary seeks to explain the process and key components of the Guidelines.

PMID- 30211675
TI  - Benefit sharing in the revised Indian National Ethical Guidelines for Biomedical
      and Health Research Involving Human Participants.
AB  - Though not an ethical principle per se, benefit sharing is still an important
      tool to achieve justice in international research. It comes back as a transversal
      issue through the revised Indian Ethical Guidelines for Biomedical and Health
      Research Involving Human Participants (hereafter referred to as "the
      Guidelines"). The Guidelines invoke this principle with reference to the
      responsible conduct of research, ownership of biobanks and data repositories,
      informed consent process, community engagement, international collaborative
      research, and research in emergency or disasters, while using the phrase
      "maximization of benefit" instead of "benefit sharing". This approach may be seen
      as quite innovative, in that it sees benefit sharing (ie, maximisation of
      benefit) as a key ethical requirement. Unfortunately, it does not explicitly
      state that the principle is relevant to all research involving human
      participants, not only to specific situations such as biobanks, research in
      emergencies and international collaborations; rather it appears to consider the
      risk of lack of benefit sharing as mainly related to international
      collaborations. Another important drawback is the frequent use of noncommittal
      language such as "could be considered" and "may be offered". This suggests that
      the provisions with respect to benefit sharing are not mandatory and thus open to
      the discretion of different Ethics Committees. Therefore, for the Guidelines to
      become a positive model for other countries and ethics bodies, further
      elaboration of the principle and mode of implementation is needed.

PMID- 30211673
TI  - Changes in the genetic requirements for microbial interactions with increasing
      community complexity.
AB  - Microbial community structure and function rely on complex interactions whose
      underlying molecular mechanisms are poorly understood. To investigate these
      interactions in a simple microbiome, we introduced E. coli into an experimental
      community based on a cheese rind and identified the differences in E. coli's
      genetic requirements for growth in interactive and non-interactive contexts using
      Random Barcode Transposon Sequencing (RB-TnSeq) and RNASeq. Genetic requirements
      varied among pairwise growth conditions and between pairwise and community
      conditions. Our analysis points to mechanisms by which growth conditions change
      as a result of increasing community complexity and suggests that growth within a
      community relies on a combination of pairwise and higher-order interactions. Our
      work provides a framework for using the model organism E. coli as a readout to
      investigate microbial interactions regardless of the genetic tractability of
      members of the studied ecosystem.

PMID- 30211676
TI  - An analysis of India's 2017 National Ethical Guidelines for Biomedical and Health
      Research Involving Human Participants: The Social and Behavioural Sciences
      aspect.
AB  - In this commentary on Section 9 (Social and Behavioural Sciences Research for
      Health) of the National Ethical Guidelines for Biomedical and Health Research
      Involving Human Participants (2017) by the Indian Council of Medical Research
      (ICMR), we appreciate that the guidelines clarify that human beings are "research
      participants" and not merely "subjects". Further, we appreciate and commend the
      ICMR for: i) contextualising the guidelines to India's unique sociocultural and
      economic situation and ii) affirming the multidisciplinary nature of health
      research and the wide scope of social and behavioural research. However, we
      question the prominence given to the difference between biomedical research and
      other aspects of health research and the description of social and psychological
      risks and discomforts as minor risks. Finally, we suggest that the guidelines
      would express greater value and diversity of the social aspects of health if they
      recommended wider representation of these aspects in the composition of research
      ethics committees.

PMID- 30211677
TI  - Imaging features of bile duct adenoma: case series and review of literature.
AB  - PURPOSE: We aimed to evaluate the imaging features of bile duct adenoma (BDA) on
      ultrasonography (US), computed tomography (CT), and magnetic resonance imaging
      (MRI). METHODS: Retrospective search in our institution database was performed
      for histologically confirmed BDA. Their imaging studies before histologic
      confirmation were reviewed. The search identified seven adults (mean age, 52.9
      years) with histologically proven single BDA each. US (n=3), CT (n=5), and MRI
      (n=3) were performed before histologic confirmation. Additionally, a systematic
      English literature review for BDA and reported imaging findings since 2000 was
      also conducted using the following search criteria "bile duct adenoma,
      peribiliary hamartoma, biliary adenoma, CT, ultrasound, MRI" (date range:
      01/01/2000 through 08/31/2016). The imaging findings of those cases reported were
      summarized and compared with our series. RESULTS: All seven individual nodules
      were well circumscribed. Five lesions were located in the right hepatic lobe and
      two in the left hepatic lobe. On US, lesions appeared hypoechoic (n=2) and
      hyperechoic (n=1). BDA was hypodense on unenhanced CT images (n=1). On MRI, BDA
      were hypointense on T1 (n=3), hyperintense on T2 (n=3), and hyperintense on
      diffusion-weighted images (n=2). On contrast-enhanced CT and MRI, BDAs showed
      arterial phase hyperenhancement that persisted on portal venous/delayed phase
      images. CONCLUSION: BDA demonstrates characteristic arterial phase
      hyperenhancement that persisted into the portal venous and delayed phases on CT
      and MRI, which may be useful in differentiating from other hepatic lesions.

PMID- 30211678
TI  - Problem-solving breast MRI: useful or a source of new problems?
AB  - PURPOSE: We aimed to evaluate the findings and results from breast magnetic
      resonance imaging (MRI) examinations performed for problem-solving purposes due
      to inconclusive conventional imaging findings. METHODS: Imaging findings, biopsy
      and follow-up results were retrospectively evaluated for breast MRI performed for
      problem-solving purposes at our department between January 2011 and December 2016
      for cases whose mammography, tomosynthesis, or ultrasonography findings were
      inconclusive. RESULTS: Lesions were identified in 414 of 986 problem-solving MRI
      examinations, and 13.3% of these lesions were diagnosed as malignant. A total of
      124 lesions were additionally found by MRI, and 9.7% of these lesions were
      diagnosed as malignant. MRI produced false-negative results in four cases. In
      cases whose conventional imaging methods yielded indefinite results, the
      sensitivity, specificity, negative and positive predictive values of MRI were
      found to be 96.3%, 83%, 99.3%, and 46.5%, respectively. For the additional
      lesions identified, the sensitivity, specificity, negative and positive
      predictive values of MRI were found to be 91.7%, 69%, 98.7%, and 24%,
      respectively. CONCLUSION: Breast MRI is a reliable problem-solving method for
      excluding malignancy that cannot be confirmed by conventional imaging. In such
      cases, additional findings from MRI may help identify new cancers that cannot be
      detected with conventional methods. However, it has moderately low specificity
      which may cause unnecessary biopsies, follow-ups, and anxiety to patients.

PMID- 30211679
TI  - Usefulness of fusion images of unenhanced and contrast-enhanced arterial phase
      cone-beam CT in the detection of viable hepatocellular carcinoma during
      transarterial chemoembolization.
AB  - PURPOSE: We aimed to evaluate the diagnostic efficacy of fusion imaging of
      unenhanced and arterial phase contrast-enhanced cone-beam computed tomography
      (CBCT) by comparing with multidetector computed tomography (MDCT) in detection of
      viable hepatocellular carcinoma (HCC) in patients who have been previously
      treated with transarterial chemoembolization (TACE). METHODS: In this
      retrospective study, a total of 173 tumors in 33 known HCC patients (21 men, 12
      women; mean age, 64+/-7.6 years; mean tumor size, 2.15+/-1.70 cm) who had been
      previously treated with TACE and underwent additional session of TACE were
      included. The sensitivity and positive predictive values of preprocedural MDCT
      and fusion CBCT for detection of viable tumor were analyzed with follow-up MDCT
      images performed 3-4 weeks after TACE, as reference standard. RESULTS: A total of
      141 remote and 32 marginal viable tumors were included. The sensitivities for
      detection of remote, marginal, and total viable tumors were 80.9%, 68.8%, and
      78.6% for MDCT and 96.5%, 96.9%, and 96.5% for fusion CBCT, respectively. The
      positive predictive values for detection of remote, marginal, and total viable
      tumors were 95.0%, 78.6%, and 95.8% for MDCT, and 97.1%, 88.6%, and 97.7% for
      fusion CBCT, respectively. Fusion CBCT showed statistically higher sensitivity
      and positive predictive value for detection of viable tumors (P < 0.001).
      CONCLUSION: The diagnostic performance of fusion imaging of unenhanced and
      contrast-enhanced arterial phase CBCT was superior to MDCT for detection of
      viable HCCs.

PMID- 30211680
TI  - Impact on genitourinary function and quality of life following focal irreversible
      electroporation of different prostate segments.
AB  - PURPOSE: We aimed to evaluate the genitourinary function and quality of life
      (QoL) following the ablation of different prostate segments with irreversible
      electroporation (IRE) for localized prostate cancer (PCa). METHODS: Sixty
      patients who received primary focal IRE for organ-confined PCa were recruited for
      this study. Patients were evaluated for genitourinary function and QoL per
      prostate segment treated (anterior vs. posterior, apex vs. base vs. apex-to-base,
      unilateral vs. bilateral). IRE system settings and patient characteristics were
      compared between patients with preserved vs. those with impaired erectile
      function and urinary continence. Data were prospectively collected at baseline,
      3, 6, and 12 months using the expanded prostate cancer index composite, American
      Urological Association symptom score, SF-12 physical and mental component summary
      surveys. Difference over time within segments per questionnaire was evaluated
      using the Wilcoxon's signed rank test. Outcome differences between segments were
      assessed using covariance models. Baseline measurements included questionnaire
      scores, age, and prostate volume. RESULTS: There were no statistically
      significant changes over time for overall urinary (P = 0.07-0.89), bowel (P =
      0.06-0.79), physical (P = 0.18-0.71) and mental (P = 0.45-0.94) QoL scores within
      each segment. Deterioration of sexual function scores was observed at 6 months
      within each segment (P = 0.001-0.16). There were no statistically significant
      differences in QoL scores between prostate segments (P = 0.08-0.97). Older
      patients or those with poor baseline sexual function at time of treatment were
      associated with a greater risk of developing erectile dysfunction. CONCLUSION:
      IRE is a feasible modality for all prostate segments without any significantly
      different effect on the QoL outcomes. Older patients and those with poor sexual
      function need to be counseled regarding the risk of erectile dysfunction.

PMID- 30211681
TI  - Prone transradial catheterization for combined single-session endovascular and
      percutaneous interventions: approach, technical success, safety, and outcomes in
      15 patients.
AB  - PURPOSE: We aimed to report approach, safety, technical success, and clinical
      outcomes of prone trans- radial access (PTRA) and demonstrate feasibility for
      procedures requiring simultaneous arterial intervention and prone percutaneous
      access. METHODS: Fifteen patients underwent PTRA, seven females (47%) and eight
      males (53%), mean age of 55 years (range, 19-78 years). All patients underwent
      PTRA for combined transarterial and posterior-approach percutaneous
      interventions. Variables included sheath size (French, F), type of anesthesia,
      arterial intervention technical success, posterior-approach percutaneous
      intervention technical success, estimated blood loss (mL), fluoroscopy and
      procedure time, complications, and follow-up. RESULTS: Mean sheath size was 4 F
      (range, 4-6 F; SD = 0.5). Arterial interventions included transarterial
      embolization of renal (n=6), hepatic (n=2), and pelvic vessels (n=2), diagnostic
      arteriography (n=4), and embolization of an arteriovenous malformation (n=1).
      Posterior-approach intervention technical success was 100% (15/15). PTRA
      technical success was 100% (15/15). Posterior-approach percutaneous interventions
      included retroperitoneal (n=5) and pelvic (n=1) mass biopsies, nephrostomy tube
      placement (n=2), cryoablation of pelvic (n=2) and renal (n=1) masses,
      sclerotherapy of arteriovenous malformations (n=2), foreign body removal from the
      renal collecting system (n=2), ablation of a renal tumor (n=1), intracavitary
      injection of pulmonary mycetoma (n=1), and ablation and cementoplasty of a
      vertebral body tumor (n=1). The biopsies were diagnostic (6/6). There were no
      minor or major access-site complications. CONCLUSION: PTRA is a safe and feasible
      method for performing combined arterial and posterior approach percutaneous
      interventions without the need for repositioning.

PMID- 30211683
TI  - Clearlumen-II thrombectomy system for treatment of acute lower limb ischemia with
      underlying chronic occlusive disease.
AB  - We aimed to present a case of effective and successful endovascular treatment of
      acute lower limb thromboembolism with Clearlumen-II, a new aspiration
      thrombectomy device. Also, we emphasize the superiority of endovascular treatment
      compared with surgery, especially together with acute and chronic occlusive
      diseases, as in our case.

PMID- 30211682
TI  - Review of influential clinical factors in reducing the risk of unsuccessful MRI
      guided HIFU treatment outcome of uterine fibroids.
AB  - Magnetic resonance imaging-guided high-intensity focused ultrasound (MRI-guided
      HIFU) is an effective noninvasive treatment option for symptomatic uterine
      fibroids. However, tissue characteristics of uterine fibroids and technical
      limitations can limit the patient population that can benefit from this therapy.
      In this article, we present our literature review focusing on the influential
      clinical factors that might reduce the risk of an unsuccessful MRI-guided HIFU
      treatment outcome of uterine fibroids.

PMID- 30211684
TI  - ARFI shear-wave elastography with simulation of acute urinary tract obstruction
      in an ex vivo porcine kidney model.
AB  - METHODS: A total of 20 heparinized pig kidneys were investigated at 10
      intrapelvic hydrostatic pressure steps (0-90 mmHg). SWE (ARFI; Virtual TouchTM
      IQ, Siemens) measurements were taken at three different measuring regions and in
      two measuring sequences using a linear ultrasonography probe (9L4, Siemens).
      Median values of 10 shear-wave speed (SWS) measurements were calculated for each
      pressure step. Logarithmic transformed median SWS values were analyzed in a
      linear mixed model. RESULTS: SWS increased significantly with increasing
      intrapelvic pressure. Median SWS for all kidneys in both measuring sequences and
      all measuring regions was 1.47 m/s (interquartile range [IQR], 0.38 m/s) at 0
      mmHg, 1.94 m/s (IQR, 0.42 m/s) at 30 mmHg, 2.07 m/s (IQR, 0.43 m/s) at 60 mmHg,
      2.24 m/s (IQR, 0.49 m/s) at 90 mmHg. The correlation between pelvic pressure
      increase and median SWS values for the central parenchyma was significantly
      higher compared with the peripheral parenchyma. CONCLUSION: Acutely increased
      renal pelvic pressure correlates with increasing SWS values in ARFI elastography
      in an ex vivo porcine kidney model.

PMID- 30211685
TI  - Incidental bladder cancers found on multiparametric MRI of the prostate gland: a
      single center experience.
AB  - PURPOSE: In the era of multiparametric magnetic resonance imaging (mpMRI) of the
      prostate gland, incidental findings are occasionally discovered on imaging. We
      aimed to report our experience of detecting incidental bladder cancers on mpMRI
      of the prostate in asymptomatic patients without irritative voiding symptoms or
      microscopic or gross hematuria. METHODS: A retrospective review was performed on
      a prospectively maintained database of all men who underwent prostate mpMRI at
      our institution from 2012 to 2018. Patients who were found to have incidental
      bladder lesions were identified and baseline demographics, imaging and
      histopathologic data were recorded. All patients with incidental bladder lesion
      detection on mpMRI, not attributable to extension of prostate cancer, underwent
      cystoscopy in addition to a biopsy and/or transurethral resection of bladder
      tumor (TURBT) if warranted on cystoscopy. RESULTS: There were 3147 prostate
      mpMRIs performed during this period and 25 cases (0.8%) of incidental bladder
      lesions were detected. These patients did not have any presenting symptoms such
      as gross or microscopic hematuria to prompt bladder lesion workup. The largest
      diameter of incidentally discovered bladder lesions ranged from 0.4 cm to 1.7 cm.
      Of the 25 cases of incidental bladder lesions, five were suspected to be due to
      prostate cancer invasion into the bladder. Only two of these five patients
      underwent biopsy, which confirmed prostate adenocarcinoma in both cases. Of the
      20 patients without suspected prostate cancer invasion of the bladder, four had
      no suspicious lesions on cystoscopy to warrant a biopsy. The remaining 16
      patients had bladder lesions seen on cystoscopy and underwent a biopsy and/or
      TURBT. Three of these patients had benign features on pathology (urachal remnant,
      amyloidosis and inflammation) and the remaining 13 had stage Ta urothelial
      carcinoma. Seven of these patients had low-grade Ta tumors and six had high-grade
      Ta tumors. All patients were treated with standard management of TURBT with or
      without intravesical BCG. There have been no reported cases of recurrence or
      progression in any of the patients in our cohort at the median follow-up of 26
      months (interquartile range,19-40 months). CONCLUSION: mpMRI of the prostate may
      yield incidental findings, such as small bladder tumors. Awareness of the
      possibility of incidental bladder lesions is important as 65% of lesions reported
      in the bladder, not attributable to extension of prostate cancer, proved to be
      bladder cancer. This may allow for early intervention for asymptomatic patients
      with undetected bladder cancer prior to disease progression.

PMID- 30211686
TI  - Mimicking of five human senses using nanostructured ZnO single material.
AB  - We demonstrated a single-material multifunctional sensor using ZnO nanorods,
      which is capable of mimicking the five human senses. A simple method for the
      growth of ZnO nanorods and their application as a multifunctional sensor was
      studied. High-density ZnO nanorods were synthesized by the carbothermal transport
      method on a graphene catalyst. To optimize the sensing mechanisms, we
      investigated ZnO nanostructure growth under two oxygen flow rates. ZnO nanorods
      as sensors for smell, light, sound, touch, and taste, the five human senses,
      showed stable electrical signals under standard ambient conditions.

PMID- 30211688
TI  - Cardiac anomaly detection based on time and frequency domain features using tree
      based classifiers.
AB  - OBJECTIVE: Recent advantages in mHealth-enabled ECG recorders boosted the demand
      for algorithms, which are able to automatically detect cardiac anomalies with
      high accuracy. APPROACH: We present a combined method of classical signal
      analysis and machine learning which has been developed during the Computing in
      Cardiology Challenge (CinC) 2017. Almost 400 hand-crafted features have been
      developed to reflect the complex physiology of cardiac arrhythmias and their
      appearance in single-channel ECG recordings. For the scope of this article, we
      performed several experiments on the publicly available challenge dataset to
      improve the classification accuracy. We compared the performance of two tree
      based algorithms-gradient boosted trees and random forests-using different
      parameters for learning. We assessed the influence of five different sets of
      training annotations on the classifiers performance. Further, we present a new
      web-based ECG viewer to review and correct the training labels of a signal data
      set. Moreover, we analysed the feature importance and evaluated the model
      performance when using only a subset of the features. The primary data source
      used in the analysis was the dataset of the CinC 2017, consisting of 8528 signals
      from four classes. Our best results were achieved using a gradient boosted tree
      model which worked significantly better than random forests. MAIN RESULTS:
      Official results of the challenge follow-up phase provided by the Challenge
      organizers on the full hidden test set are 90.8% (Normal), 84.1% (AF), 74.5%
      (Other), resulting in a mean F1-score of 83.2%, which was only 1.6% behind the
      challenge winner and 0.2% ahead of the next-best algorithm. Official results were
      rounded to two decimal places which lead to the equal-second best F1 F -score of
      83% with five others. SIGNIFICANCE: The algorithm achieved the second-best score
      among 80 algorithms of the Challenge follow-up phase equal with five others.

PMID- 30211689
TI  - Nanoparticles based on disulfide-containing poly(beta-amino ester) and
      zwitterionic fluorocarbon surfactant as a redox-responsive drug carrier for brain
      tumor treatment.
AB  - Malignant brain tumors are often characterized by rapid growth, high invasiveness
      and poor prognosis. Current methods for brain tumor treatment are dramatically
      limited because of their inability to cross the blood-brain barrier (BBB) and
      enter the tumor cells. In this study, we prepared redox-responsive nanoparticles
      based on disulfide-containing poly(beta-amino ester) (ssPBAE) and a zwitterionic
      fluorocarbon surfactant (Intechem-02) that has a carboxybetaine moiety in
      molecular structure, and preliminarily evaluated their potential as a drug
      carrier for brain tumor treatment. These nanoparticles, named as ssPBAEI, had a
      regular spherical shape and a small size below 50 nm with a relative narrow
      distribution. Doxorubicin (DOX), as a model chemotherapeutic drug, was
      efficiently encapsulated into ssPBAEI nanoparticles with a loading content of
      25.4%. DOX-loaded ssPBAEI nanoparticles (ssPBAEI/DOX) showed significant redox
      responsive in vitro release property and successfully carried DOX across a BBB
      model, monolayer of human brain capillary endothelial hCMEC/D3 cells. In human
      glioma LN229 cells, ssPBAEI/DOX nanoparticles were efficiently internalized and
      DOX was successfully released afterwards, thus significantly inhibited cell
      growth and induced cell apoptosis. In summary, this nanoparticle system based on
      ssPBAE and Intechem-02 showed a great potential as a drug carrier for brain tumor
      treatment.

PMID- 30211687
TI  - Methods for fabrication and evaluation of a 3D microengineered model of
      myelinated peripheral nerve.
AB  - OBJECTIVE: The cost and low success rates of the neurological drug development
      pipeline have diverted the pharmaceutical industry to 'nerve-on-a-chip' systems
      as preclinical models to streamline drug development. We present a novel micro
      engineered 3D hydrogel platform for the culture of myelinated embryonic
      peripheral neural tissue to serve as an effective in vitro model for
      electrophysiological and histological analysis that could be adopted for
      preclinical testing. APPROACH: Dorsal root ganglions (DRG) from 15 d old
      embryonic rats were cultured in 3D hydrogel platforms. The interaction between
      Schwann cells (SC) and neurons during axonal development and regeneration affects
      the direction of growth and the synthesis of myelin sheaths. Induction of
      myelination was performed with two approaches: the addition of exogenous SC and
      promoting migration of endogenous SC. MAIN RESULTS: Histological analysis of the
      preparation utilizing exogenous SC showed aligned, highly fasciculated axonal
      growth with noticeable myelin sheaths around axons. Separately,
      electrophysiological testing of the preparation utilizing endogenous SC showed
      increased amplitude of the compound action potential and nerve conduction
      velocity in the presence of ascorbic acid (AA). SIGNIFICANCE: This platform has
      immense potential to be a useful and translatable in vitro testing tool for drug
      discovery and myelination studies.

PMID- 30211690
TI  - An automatic algorithm to exploit the symmetries of the system response matrix in
      positron emission tomography iterative reconstruction.
AB  - Positron emission tomography (PET) iterative 3D reconstruction is a very
      computational demanding task. One of the main issues of the iterative
      reconstruction concerns the management of the system response matrix (SRM). The
      SRM models the relationship between the projection and the voxel space and its
      memory footprint can easily exceed hundreds of GB. Moreover, in order to make the
      reconstruction fast enough not to hinder its practical application, the SRM must
      be stored in the random access memory of the workstation used for the
      reconstruction. This issue is normally solved by implementing efficient storage
      schemes and by reducing the number of redundant patterns in the SRM through
      symmetries. However, finding a sufficient number of symmetries is often non
      trivial and is typically performed using dedicated solutions that cannot be
      exported to different detectors and geometries. In this paper, an automatic
      approach to reduce the memory footprint of a pre-computed SRM is described. The
      proposed approach was named symmetry search algorithm (SSA) and consists in an
      algorithm that searches for some of the redundant patterns present in the SRM,
      leading to its lossy compression. This approach was built to detect translations,
      reflections and coordinates swap in voxel space. Therefore, it is particularly
      well suited for those scanners where some of the rotational symmetries are
      broken, e.g. small animal scanner where the modules are arranged in a polygonal
      ring made of few elements, and dual head planar PET systems. In order to validate
      this approach, the SSA is applied to the SRM of a preclinical scanner (the IRIS
      PET/CT). The data acquired by the scanner were reconstructed with a dedicated
      maximum likelihood estimation maximization algorithm with both the uncompressed
      and the compressed SRMs. The results achieved show that the information lost due
      to the SSA compression is negligible. Compression factors up to 52 when using the
      SSA together with manually inserted symmetries and up to 204 when using the SSA
      alone, can be obtained for the IRIS SRM. These results come without significant
      differences in the values and in the main quality metrics of the reconstructed
      images, i.e. spatial resolution and noise. Although the compression factors
      depend on the system considered, the SSA is applicable to any SRM and therefore
      it can be considered a general tool to reduce the footprint of a pre-computed
      SRM.

PMID- 30211691
TI  - Terahertz rectifier exploiting electric field-induced hot-carrier effect in
      asymmetric nano-electrode.
AB  - Rectifiers have been used to detect electromagnetic waves with very low photon
      energies. In these rectifying devices, different methods have been utilized, such
      as adjusting the bandgap and the doping profile, or utilizing the contact
      potential of the metal-semiconductor junction to produce current flow depending
      on the direction of the electric field. In this paper, it is shown that the
      asymmetric application of nano-electrodes to a metal-semiconductor-metal (MSM)
      structure can produce such rectification characteristics, and a terahertz (THz)
      wave detector based on the nano-MSM structure is proposed. Integrated with a
      receiving antenna, the fabricated device detects THz radiation up to a frequency
      of 1.5 THz with responsivity and noise equivalent power of 10.8 V/W and [Formula:
      see text] respectively, estimated at 0.3 THz. The unidirectional current flow is
      attributed to the thermionic emission of hot carriers accelerated by the locally
      enhanced THz field at the sharp end of the nano-electrode. This work not only
      demonstrates a new type of THz detector but also proposes a method for
      manipulating ultrafast charge-carrier dynamics through the field enhancement of
      the nano-electrode, which can be applied to ultrafast photonic and electronic
      devices.

PMID- 30211692
TI  - Directly probing the dissociation effects of graphene oxide nanosheets on hIAPP
      fibrils.
AB  - The aggregation of human islet amyloid polypeptides (hIAPP) to mature fibrils is
      considered as the main cause of type II diabetes. Therefore destroying the pre
      formed hIAPP fibrils is expected to be a promising strategy for therapeutic
      treatments. In this work, the dissociation effects of graphene oxide (GO)
      nanosheets on hIAPP mature fibrils are investigated. The results clearly
      demonstrate that hIAPP fibrils can be quickly adsorbed on the GO surface and
      efficiently broken into short fragments. Meanwhile, the beta-sheet structures of
      hIAPP fibrils are greatly destroyed. Particularly, in situ atomic force
      microscopy was applied to monitor the real-time interaction between hIAPP fibrils
      and GO nanosheets. It provides distinct evidence that the disruption of hIAPP
      fibrils by GO nanosheets mainly occurs at the GO edges. Size-dependent
      experiments further justify the interfere of edge contribution, which suggest
      small-sized GO nanosheets exhibit better dissociation ability than large-sized
      ones. Therefore, this study not only provides valuable information that GO
      nanosheets (especially small-sized ones) can act as efficient nanoblades to break
      hIAPP fibrils, but also suggests a powerful and widely available methodology for
      investigating real-time interaction between nanomaterials and biomolecules.

PMID- 30211693
TI  - Tracer diffusion in crowded narrow channels.
AB  - We summarise different results on the diffusion of a tracer particle in lattice
      gases of hard-core particles with stochastic dynamics, which are confined to
      narrow channels-single-files, comb-like structures and quasi-one-dimensional
      channels with the width equal to several particle diameters. We show that in such
      geometries a surprisingly rich, sometimes even counter-intuitive, behaviour
      emerges, which is absent in unbounded systems. This is well-documented for the
      anomalous diffusion in single-files. Less known is the anomalous dynamics of a
      tracer particle in crowded branching single-files-comb-like structures, where
      several kinds of anomalous regimes take place. In narrow channels, which are
      broader than single-files, one encounters a wealth of anomalous behaviours in the
      case where the tracer particle is subject to a regular external bias: here, one
      observes an anomaly in the temporal evolution of the tracer particle velocity,
      super-diffusive at transient stages, and ultimately a giant diffusive broadening
      of fluctuations in the position of the tracer particle, as well as spectacular
      multi-tracer effects of self-clogging of narrow channels. Interactions between a
      biased tracer particle and a confined crowded environment also produce peculiar
      patterns in the out-of-equilibrium distribution of the environment particles,
      very different from the ones appearing in unbounded systems. For moderately dense
      systems, a surprising effect of a negative differential mobility takes place,
      such that the velocity of a biased tracer particle can be a non-monotonic
      function of the force. In some parameter ranges, both the velocity and the
      diffusion coefficient of a biased tracer particle can be non-monotonic functions
      of the density. We also survey different results obtained for a tracer particle
      diffusion in unbounded systems, which will permit a reader to have an
      exhaustively broad picture of the tracer diffusion in crowded environments.

PMID- 30211694
TI  - A neural mass model to predict electrical stimulation evoked responses in human
      and non-human primate brain.
AB  - OBJECTIVE: Deep brain stimulation (DBS) is a valuable tool for ameliorating drug
      resistant pathologies such as movement disorders and epilepsy. DBS is also being
      considered for complex neuro-psychiatric disorders, which are characterized by
      high variability in symptoms and slow responses that hinder DBS setting
      optimization. The objective of this work was to develop an in silico platform to
      examine the effects of electrical stimulation in regions neighboring a stimulated
      brain region. APPROACH: We used the Jansen-Rit neural mass model of single and
      coupled nodes to simulate the response to a train of electrical current pulses at
      different frequencies (10-160 Hz) of the local field potential recorded in the
      amygdala and cortical structures in human subjects and a non-human primate.
      RESULTS: We found that using a single node model, the evoked responses could be
      accurately modeled following a narrow range of stimulation frequencies. Including
      a second coupled node increased the range of stimulation frequencies whose evoked
      responses could be efficiently modeled. Furthermore, in a chronic recording from
      a non-human primate, features of the in vivo evoked response remained consistent
      for several weeks, suggesting that model re-parameterization for chronic
      stimulation protocols would be infrequent. SIGNIFICANCE: Using a model of neural
      population activity, we reproduced the evoked response to cortical and
      subcortical stimulation in human and non-human primate. This modeling framework
      provides an environment to explore, safely and rapidly, a wide range of
      stimulation settings not possible in human brain stimulation studies. The model
      can be trained on a limited dataset of stimulation responses to develop an
      optimal stimulation strategy for an individual patient.

PMID- 30211695
TI  - Comparison of logistic regression, support vector machines, and deep learning
      classifiers for predicting memory encoding success using human intracranial EEG
      recordings.
AB  - OBJECTIVE: We sought to test the performance of three strategies for binary
      classification (logistic regression, support vector machines, and deep learning)
      for the problem of predicting successful episodic memory encoding using direct
      brain recordings obtained from human stereo EEG subjects. We also sought to test
      the impact of applying t-distributed stochastic neighbor embedding (tSNE) for
      unsupervised dimensionality reduction, as well as testing the effect of reducing
      input features to a core set of memory relevant brain areas. This work builds
      upon published efforts to develop a closed-loop stimulation device to improve
      memory performance. APPROACH: We used a unique data set consisting of 30 stereo
      EEG patients with electrodes implanted into a core set of five common brain
      regions (along with other areas) who performed the free recall episodic memory
      task as brain activity was recorded. Using three different machine learning
      strategies, we trained classifiers to predict successful versus unsuccessful
      memory encoding and compared the difference in classifier performance (as
      measured by the AUC) at the subject level and in aggregate across modalities. We
      report the impact of feature reduction on the classifiers, including reducing the
      number of input brain regions, frequency bands, and the impact of tSNE. RESULTS:
      Deep learning classifiers outperformed both support vector machines (SVM) and
      logistic regression (LR). A priori selection of core brain regions also improved
      classifier performance for LR and SVM models, especially when combined with tSNE.
      SIGNIFICANCE: We report for the first time a direct comparison among traditional
      and deep learning methods of binary classification to the problem of predicting
      successful memory encoding using human brain electrophysiological data. Our
      findings will inform the design of brain machine interface devices to affect
      memory processing.

PMID- 30211696
TI  - An investigation into setting the blood flow restriction pressure based on
      perception of tightness.
AB  - OBJECTIVE: To determine whether the perceived tightness scale could be used to
      set sub-occlusive blood flow restriction pressures. A secondary aim was to
      determine variables that may impact individual ratings. APPROACH: One hundred and
      twenty participants completed three separate conditions in one limb within the
      upper and lower body. Participants were asked to rate their perceived tightness
      for two of the three conditions, regarded as moderate pressure without pain
      (7/10) and intense pressure with pain (10/10). A third condition, arterial
      occlusion pressure, was completed that required no rating from participants.
      Order of conditions and limb assignment were randomized for each participant.
      Measurements for muscle and fat thickness along with limb circumference were
      completed on the tested limbs. MAIN RESULTS: Order of conditions did not affect
      results in the upper or lower body. A condition effect was found for the upper
      body with the 7/10 rating lower than the arterial occlusion pressure [7/10: 132
      (38) mmHg  <  Arterial Occlusion: 162 (24) mmHg  <  10/10: 202 (46) mmHg]. A
      condition effect was also found for the lower body with 7/10 condition [120 (33)
      mmHg] rating lower than arterial occlusion pressure [171 (28) mmHg] and 10/10
      condition [178 (49) mmHg]. However, there was a non-significant difference
      between the arterial occlusion pressure and the 10/10 condition (difference of 7(
      3, 18) mmHg, (P  =  0.159). SIGNIFICANCE: Participants appear adept in their
      ability to rate sub-occlusive pressure based upon perceived tightness. Findings
      from this study provide some support for the utility of this method as a means
      for completion of practical blood flow restriction, whereby individuals tighten
      the cuff based upon their relative perceptual response.

PMID- 30211697
TI  - Multi-objective particle swarm optimization for postoperative deep brain
      stimulation targeting of subthalamic nucleus pathways.
AB  - OBJECTIVE: The effectiveness of deep brain stimulation (DBS) therapy strongly
      depends on precise surgical targeting of intracranial leads and on clinical
      optimization of stimulation settings. Recent advances in surgical targeting,
      multi-electrode designs, and multi-channel independent current-controlled
      stimulation are poised to enable finer control in modulating pathways within the
      brain. However, the large stimulation parameter space enabled by these
      technologies also poses significant challenges for efficiently identifying the
      most therapeutic DBS setting for a given patient. Here, we present a
      computational approach for programming directional DBS leads that is based on a
      non-convex optimization framework for neural pathway targeting. APPROACH: The
      algorithm integrates patient-specific pre-operative 7 T MR imaging, post
      operative CT scans, and multi-objective particle swarm optimization (MOPSO)
      methods using dominance based-criteria and incorporating multiple neural pathways
      simultaneously. The algorithm was evaluated on eight patient-specific models of
      subthalamic nucleus (STN) DBS to identify electrode configurations and
      stimulation amplitudes to optimally activate or avoid six clinically relevant
      pathways: motor territory of STN, non-motor territory of STN, internal capsule,
      superior cerebellar peduncle, thalamic fasciculus, and hyperdirect pathway. MAIN
      RESULTS: Across the patient-specific models, single-electrode stimulation showed
      significant correlations across modeled pathways, particularly for motor and non
      motor STN efferents. The MOPSO approach was able to identify multi-electrode
      configurations that achieved improved targeting of motor STN efferents and
      hyperdirect pathway afferents than that achieved by any single-electrode
      monopolar setting at equivalent power levels. SIGNIFICANCE: These results suggest
      that pathway targeting with patient-specific model-based optimization algorithms
      can efficiently identify non-trivial electrode configurations for enhancing
      activation of clinically relevant pathways. However, the results also indicate
      that inter-pathway correlations can limit selectivity for certain pathways even
      with directional DBS leads.

PMID- 30211698
TI  - Accessibility of the pores in highly porous alumina films synthesized via
      sequential infiltration synthesis.
AB  - Inorganic nanoporous materials with highly accessible pores are of great interest
      for the design of efficient catalytic, purification and detection systems.
      Limited access to the pores is a common problem associated with traditional
      approaches for the synthesis of porous materials, affecting the functionality of
      the low-density structure. Recently, infiltration of a nanoporous polymer
      template with inorganic precursors followed by oxidative annealing was proposed
      as a new and efficient approach to creating porous inorganic structures with
      controlled thickness, composition and pore sizes. Here, we report an ultra-high
      accessibility of the pores in porous films prepared via polymer-swelling-assisted
      sequential infiltration synthesis (SIS). Using a quartz crystal microbalance
      technique, we show the increased solvent adsorbing capabilities of highly porous
      alumina films as a result of high interconnectivity of the pores in such
      structures. The directionality and highly interconnected nature of the pores are
      demonstrated in experiments with the partial blocking of pore access by the
      deposition of a single-layer graphene that is not transparent to solvent. 60% of
      the pores remain accessible when only 20% of the surface is exposed to solvent.
      Using humidity detection as an example, we also show that highly porous alumina
      produced by polymer-swelling-assisted SIS is a promising candidate for sensing
      applications.

PMID- 30211699
TI  - TiO2 seeded on nitrogen-doped porous carbon nanofibers for superior
      electrochemical performance as freestanding anodes of lithium-ion batteries.
AB  - Fibrous mats piled by nitrogen-doped porous carbon nanofibers with seeded TiO2
      are fabricated and punched directly into circles as lithium-ion battery anodes.
      The seeding structure is composed of semi-wrapped TiO2 nanoparticles on carbon
      nanofibers (CNFs) coated with a thin layer of carbon. Synchronously, pores with
      various widths are formed on CNFs. As a freestanding anode, an initial discharge
      capacity of 615 mAh g-1 with a coulombic efficiency of 56% is reached, and 322
      mAh g-1 is obtained after 100 cycles at a current density of 100 mA g-1. This is
      assigned to the increasing number of active sites for the lithium ion from pores
      with various widths and improved conductivity originating from nitrogen doping.
      Superior rate performance (179 mAh g-1 at the current density of 2000 mA g-1)
      under various current densities compared with that of other counterparts is
      attributed to the structural stability originating from the seeding structure
      with the help of the C-O-Ti bond. An additional 800 cycles are displayed at the
      current density of 2000 mA g-1, and superior stability is also exhibited.

PMID- 30211700
TI  - Role of GO and r-GO in resistance switching behavior of bilayer TiO2 based RRAM.
AB  - Graphene-based resistance random access memory devices (RRAMs) have shown promise
      as a suitable replacement for flash memories, owing to their fast switching
      speed, low programming voltage, better scalability and great reliability.
      Furthermore, recent research works have shown bi-layer RRAM devices exhibiting
      better performance along the same parameters, where titania is one of the most
      commonly used materials. In the present work, we have studied the resistance
      switching behavior in a bi-layer RRAM device structure of TiO2 with graphene
      oxide (GO) and reduced graphene oxide (rGO). Switching mechanism in these devices
      has been investigated by detailed experimental characterization in conjunction
      with a finite element modeling (FEM) simulation. A dual conical conductive
      filament has been used in the present work, based on the modeling of the
      electroforming process carried out by FEM. It has been demonstrated that for the
      GO/TiO2 based hybrid RRAM device structure, GO acts as an active filament
      formation layer, whereas in the rGO/TiO2 bi-layer structure, rGO acts as a mere
      electrode.

PMID- 30211701
TI  - Pegloticase-Associated Hemolysis.

PMID- 30211702
TI  - CE: The Use of Resuscitative Endovascular Balloon Occlusion of the Aorta in
      Treating Hemorrhagic Shock from Severe Trauma.
AB  - : Hemorrhage is the leading cause of preventable death in trauma patients. In
      recent years, technological innovations and research efforts aimed at preventing
      death from hemorrhagic shock have resulted in the emergence of resuscitative
      endovascular balloon occlusion of the aorta (REBOA). REBOA offers a less invasive
      option for emergent hemorrhage control in noncompressible areas of the body
      without the added risks and morbidities of an ED thoracotomy. This article
      outlines the procedure and device used, describes the procedure's evolution, and
      discusses various considerations, pitfalls, and nursing implications.

PMID- 30211703
TI  - CE: Acute Pain Management for People with Opioid Use Disorder.
AB  - : Medication-assisted treatment for opioid use disorder (OUD), which incorporates
      methadone, buprenorphine, or naltrexone, has been shown to reduce all-cause
      mortality rates in patients with this disease-and the numbers of patients
      receiving such treatment is substantial. In 2016, among U.S. patients with OUD,
      nearly 350,000 were treated with methadone, more than 60,000 were treated with
      buprenorphine, and more than 10,000 were treated with naltrexone. Managing acute
      pain in patients receiving this treatment can be a significant nursing challenge.
      The authors discuss the attributes of the three medications used to treat OUD
      and, through a composite patient case, review how to manage acute pain
      effectively in patients receiving this type of treatment.This article is one in a
      series on palliative care developed in collaboration with the Hospice and
      Palliative Nurses Association (https://advancingexpertcare.org), which offers
      education, certification, advocacy, leadership, and research on palliative care.

PMID- 30211706
TI  - What are the Demographics and Epidemiology of Legg-Calve-Perthes Disease in a
      Large Southern California Integrated Health System?
AB  - BACKGROUND: Although many authors have reported the incidence of Legg-Calve
      Perthes disease (LCPD), there have been few incidence studies in the United
      States on large, self-contained populations such as those within an integrated
      health system. Understanding the epidemiology and demographics of LCPD in this
      setting may help clinicians identify patients at the greatest risk and aid in
      diagnosis and subsequent treatment. QUESTIONS/PURPOSES: In this study we sought
      (1) to determine the incidence and demographics of LCPD in a large cohort of
      children and adolescents in a Southern California integrated healthcare system,
      and (2) to identify any demographic or clinical factors (such as age, sex,
      race/ethnicity, or BMI) that are independently associated with LCPD. METHODS: A
      retrospective chart analysis was done on patients diagnosed with LCPD within our
      integrated healthcare system in patients aged 2 to 12 years over a 3-year period
      between 2010-2012. There were nearly 800,000 children in this cohort. Patient
      demographics were recorded; the incidence of LCPD was determined for the entire
      group and by sex, age, and race/ethnicity. Odds ratios for an association with
      LCPD based on age, sex, BMI and race/ethnicity were determined using logistic
      regression models. RESULTS: The LCPD incidence per 100,000 for all children was
      2.84, with the highest incidence in 2- to 5-year-old children (3.05; 95% CI, 1.51
      4.59) and the lowest in 9- to 12-year-old children (1.06; 95% CI, 0.21-1.91).
      Incidence varied markedly among ethnicities, with the highest incidence in whites
      (5.69; 95% CI, 3.13-8.24) and the lowest in Asians (0.78; 95% CI, 0.00-2.32).
      Data analysis revealed a 3.13-times increased odds ratio (OR) of LCPD in 2- to 5
      year-old patients versus 9- to 12-year-olds (p = 0.011), and boys had a 12.44
      times greater OR of LCPD than girls (p < 0.001). Data analysis showed an
      increased OR for LCPD (3.41; 95% CI, 1.28-9.09) in patients with extreme obesity
      (BMI-for-age >= 1.2 * 95th percentile or a BMI >= 35 kg/m) compared with patients
      with a normal BMI. CONCLUSIONS: Our study of a large integrated healthcare system
      in Southern California revealed an increased association of male sex and young
      age (2 to 5 years old) with LCPD. The overall incidence was lower overall than
      previously reported, although the incidence seen in white patients was similar to
      that in prior studies. The finding that patients with extreme obesity may have an
      increased association with LCPD merits further study. These findings may increase
      providers' awareness of the risk of the disease in younger patients and in
      extremely obese patients, and it also merits further future investigation as to
      whether there is a cause or effect relationship between extreme obesity and LCPD.
      LEVEL OF EVIDENCE: Level IV, prognostic study.

PMID- 30211704
TI  - Subjective Cognitive Impairment and the Broad Autism Phenotype.
AB  - INTRODUCTION: Roughly 4% to 23% of the population embody stress prone personality
      and other traits characterizing a subclinical "broad autism phenotype" (BAP).
      Subjective cognitive impairment (SCI) among healthy elderly is associated with
      psychological distress leading us to predict BAP would be associated with SCI.
      METHODS: The Autism Spectrum Quotient, a self-administered 50 item questionnaire,
      was completed by 419 consecutive members of the Arizona APOE Cohort who underwent
      neuropsychological testing every 2 years. SCI was assessed with self and
      informant versions of the Multidimensional Assessment of Neurodegenerative
      Symptoms (MANS) Questionnaire. RESULTS: A total of 45 individuals scored in the
      BAP range, designated BAP+, and the rest were BAP-. At entry, both
      Multidimensional Assessment of Neurodegenerative Symptoms Questionnaire Self and
      Informant scores were higher in the BAP+ group (P<0.0001). After age 60, the BAP+
      group had greater annual increases in Multidimensional Assessment of
      Neurodegenerative Symptoms Questionnaire Self scores (0.05 vs. 0.02;
      difference=0.03; 95% confidence interval, 0.004-0.05; P=0.02) yet there was no
      difference between groups in memory decline. Over ~10 years 33 individuals
      developed mild cognitive impairment: 4 in the BAP+ group (8.9%) and 29 in the BAP
      group (7.8%), P=0.77. DISCUSSION: Individuals who meet criteria for the BAP have
      escalating SCI with age, but no greater rate of memory decline or clinical
      progression to mild cognitive impairment.

PMID- 30211707
TI  - Cochrane in CORR(r): Percutaneous Vertebroplasty for Osteoporotic Vertebral
      Compression Fracture.

PMID- 30211708
TI  - Reply to the Letter to the Editor: Art in Science: Jusepe de Ribera's Puzzle in
      The Clubfoot.

PMID- 30211709
TI  - Associations Between Musculoskeletal Pain Experience and Pressure and Cold Pain
      Sensitivity: A Community-based Cross-sectional Study of Young Adults in the Raine
      Study.
AB  - OBJECTIVES: To investigate the cross-sectional associations between
      musculoskeletal pain experience and measures of pressure and cold pain
      sensitivity in young adults from the Western Australian Pregnancy Cohort (Raine)
      Study. PARTICIPANTS AND METHODS: In total, 917 participants were eligible for
      analysis if they provided data pertaining to musculoskeletal pain status at the
      22-year follow-up and had data for at least 1 valid pain sensitivity test.
      Standardized protocols were used to assess pressure pain threshold (4 sites:
      lumbar spine, tibialis anterior, upper trapezius, and wrist) and cold pain
      threshold (wrist). Four pain experience groups ("No pain" [n=562, 61.3%], "Low"
      [n=84, 9.2%], "Medium" [n=147, 16.0%], "High" [n=124, 13.5%]) were determined by
      latent class analysis using parameters of pain chronicity, frequency, intensity,
      and number of pain areas. Variables considered as confounders included sex, age,
      ethnicity, waist-hip ratio, psychological symptoms, sleep quality, physical
      activity, sedentary behavior, smoking, and income. RESULTS: There were no
      associations between pain experience and pressure pain sensitivity after
      adjusting for confounders. The "Medium" and "High" pain experience groups
      demonstrated heightened cold pain sensitivity compared with the "No pain" group
      (P=0.023), adjusted for sex and smoking. DISCUSSION: This study provides the most
      extensive investigation of the relationship between musculoskeletal pain
      experience and pressure and cold pain sensitivity in young adults. Heightened
      cold pain sensitivity in those classified as "Medium" and "High" pain experience
      may suggest altered nociceptive processing and has implications for clinical
      management.

PMID- 30211710
TI  - Dental Implant Therapy on a Patient With von Willebrand Disease: A Case Study.
AB  - BACKGROUND: Von Willebrand disease (vWD) is the most common hereditary disorder
      affecting coagulation. Patients with this disorder are at a higher risk of
      postoperative complications after dental surgery. This article discusses the
      successful treatment for a patient with vWD undergoing implant therapy. CASE
      DESCRIPTION: A young 21-year-old patient with vWD lost tooth #30 because of
      caries and required implant therapy. Through collaboration with a hematologist
      administering prophylactic desmopressin (DDAVP), the implant surgery was
      performed without any postoperative complications. The implant successfully
      integrated and was restored into function. The successful outcome met
      expectations after careful planning and execution. PRACTICAL IMPLICATIONS:
      Collaboration with the appropriate medical providers, as well as treatment
      modifications for surgical procedures during implant therapy, is necessary for
      successful treatment of a patient with von Willebrand disorder.

PMID- 30211711
TI  - Surgical Intervention for Cauda Equina Syndrome in the Second and Third
      Trimesters of Pregnancy: A Report of Three Cases.
AB  - CASE: Low back pain affects >50% of pregnant women. However, cauda equina
      syndrome (CES) during pregnancy is rare. Because a delay in treatment increases
      the risk of irreversible neurologic damage, acute onset is regarded as a surgical
      emergency. We describe 3 cases of CES in pregnant women at 24, 27, and 30 weeks'
      gestation, respectively. CONCLUSION: All 3 of the patients underwent surgical
      decompression in the prone position under general anesthesia with continuous
      external monitoring of the fetal heart rate. Intraoperative findings were
      noteworthy for epidural venous plexus engorgement in 2 of the patients. There
      were no complications for the patients or the fetuses, and all 3 of the patients
      had postoperative resolution of the neurologic symptoms.

PMID- 30211712
TI  - Delayed Reconstruction Following Incarceration of the Medial Epicondyle in the
      Elbow Joint: A Case Report and Review of the Literature.
AB  - CASE: Neglected medial epicondylar fractures with intra-articular incarceration
      are uncommon. At 6 weeks after an elbow dislocation, an 11-year-old child was
      referred to our unit with painless, restricted range of motion. Clinical
      assessment and radiographic imaging revealed an incarcerated medial epicondylar
      fragment in the ulnohumeral joint. We performed open reduction and internal
      fixation (ORIF) and transposed the ulnar nerve. The clinical and radiographic
      outcomes at the final follow-up were excellent. CONCLUSION: The management of
      neglected pediatric medial epicondylar fractures with intra-articular
      incarceration is challenging. Identifying the fractured fragment is essential.
      Although the outcome following excision is variable, children who have undergone
      ORIF with ulnar nerve transposition have regained full function, despite delayed
      reconstruction.

PMID- 30211713
TI  - Sirolimus Therapy as Perioperative Treatment of Gorham-Stout Disease in the
      Thoracic Spine: A Case Report.
AB  - CASE: Gorham-Stout disease (GSD) is a rare entity that is marked by progressive
      osteolysis and bone resorption. A 14-year-old boy who was being followed for
      scoliosis presented with a marked curve progression and kyphoscoliosis. Imaging
      revealed osteolysis of the posterior elements and the ribs, suggestive of GSD.
      The structural compromise threatened spinal cord compression. Preoperative
      sirolimus therapy was initiated to stabilize the disease prior to corrective
      instrumentation. A biopsy specimen that was obtained at the time of
      instrumentation showed lymphatic vascular spaces consistent with GSD. Sirolimus
      therapy with the addition of bisphosphonate therapy was continued
      postoperatively. CONCLUSION: To our knowledge, this case report is the first to
      describe sirolimus therapy combined with surgery for GSD of the spine. The
      patient did well with consecutive medical optimization and surgical intervention,
      including postoperative sirolimus and bisphosphonate therapy.

PMID- 30211714
TI  - Valgus Osteotomy with Plate-and-Nail Fixation for the Treatment of Proximal
      Femoral Deformities Due to Fibrous Dysplasia: A Report of Two Cases.
AB  - CASE: We describe 2 cases of proximal femoral deformity due to fibrous dysplasia
      that were corrected with osteotomies and a novel combined construct with a blade
      plate and a retrograde intramedullary nail. CONCLUSION: A single-stage procedure
      using a combined construct with a blade plate and a retrograde intramedullary
      nail is a viable option for correcting and subsequently preventing proximal
      femoral deformities due to fibrous dysplasia.

PMID- 30211715
TI  - Physiatry as a Leader for Post Acute Care in Integrated Healthcare Systems.
AB  - As health care is being moved to a higher level of accountability, there has been
      a focus on improving outcomes through improving post acute care. The issues of
      cost and readmissions to acute care settings are very important, but the focus on
      patient function has not been foremost. Due to the fact that most post acute care
      needs are based on functional limitations, and that physiatrists are well versed
      in transitions of care, rehabilitation of patients back to community settings,
      team building, and leadership, it is appropriate for rehabilitation medicine to
      take a leadership role in the planning and development of post acute care
      services in the new integrated healthcare systems that are becoming prevalent in
      healthcare. This review discusses some of the issues in post acute care, the
      growth of the integrated health system model, and how there are opportunities and
      challenges for physiatric leadership to help develop these new models of care.

PMID- 30211716
TI  - Quantification and Description of Physical Exercise Performance.

PMID- 30211717
TI  - Physiatry Reviews for Evidence in Practice (PREP).

PMID- 30211718
TI  - Depression Characterization and Race among Stroke Survivors Receiving Inpatient
      Rehabilitation.
AB  - Race and ethnicity play a significant role in post-stroke outcomes. This brief
      report describes the presence of depression among stroke survivors who received
      inpatient rehabilitation and whether depression differs by race. Data from
      eRehabData(r) and electronic medical records were analyzed for patients who
      received rehabilitation after an acute ischemic or hemorrhagic stroke. Of 1501
      stroke patients, 61.3% were White, 33.9% were African American (AA) and 4.8% were
      of other race/ethnic backgrounds. By retrospective clinical review, depression
      was documented for 29.7% of stroke patients. Pre-morbid versus new onset of post
      stroke depression was documented for 13.4% and 21.6% of Whites, 7.5% and 11.5% of
      AA, and 0% and 16.7% of patients of other race/ethnic groups. Compared with
      Whites, AA and people of other races had a lower odds of post-stroke depression
      (AA adjusted odds ratio [OR]=0.52, 95% confidence interval [CI]=0.41-0.68; other
      races OR=0.37, 95% CI=0.19-0.71), after adjusting for all other significant risk
      factors identified in the bivariate analysis (sex, hyperlipidemia, cognitive
      deficit, neglect). Depression was documented for one in three stroke survivors
      who received inpatient rehabilitation, and highest among Whites especially for
      pre-stroke depression. Addressing depression in rehabilitation care needs to
      consider individual patient characteristics and pre-stroke health status.

PMID- 30211719
TI  - Multi-system balance training reduces injurious fall risk in Parkinson's disease 
      A randomized trial.
AB  - Previous studies have shown that balance training could reduce falls in people
      with Parkinson's disease (PD). However, it remains unclear whether exercise can
      reduce injurious falls. The objective of present study was to determine whether
      multi-system balance training could reduce injurious falls and modify targeted
      fall risk factors in PD non-fallers and single fallers. Participants were
      randomly assigned to an 8-week balance group [Experimental (EXP), N=41] or an
      upper limbs group [Control (CON), N=43]. Outcomes examined at post-training
      (Post) and 12-month follow-up (FU12m) were:1) injurious fall risk (ratio of non
      injurious fallers to injurious fallers); 2) two potential fall risk factors based
      on Balance Evaluation Systems Test (BESTest) scores and dual-task timed-up-and-go
      (DTUG) times. At Post, results indicated that there were no injurious falls, and
      fewer EXP participants were found in high fall-risk cohorts based on BESTest
      scores and DTUG times (p<0.05). At FU12m, the number of injurious fallers was
      lower in EXP group (p<0.05). There was also a marginally lower percentage of EXP
      group in the high fall-risk cohort based on BESTest scores (p=0.059). The
      findings conclude that multi-system balance training potentially reduces
      injurious fall risk up to 12 months post-training and lowers balance-related fall
      risks in people with PD.

PMID- 30211720
TI  - Short article: Outcome of medical and surgical management for perforated jejunal
      diverticulitis.
AB  - OBJECTIVES: Perforated jejunal diverticulitis (PJD) is rare, but it has high
      mortality rates. The role of nonsurgical management is debated. The aim of this
      study is to assess the outcomes of medical and surgical management of PJD.
      PATIENTS AND METHODS: A single-centre study on a series of emergency patients
      diagnosed with PJD between 2010 and 2016 was conducted. RESULTS: Eleven patients
      with PJD were treated (seven women). Nine out of 11 were diagnosed by a computed
      tomography scan, and two were diagnosed at laparotomy. The initial approach was
      medical treatment in five patients, based on clinical and imaging findings. Four
      (80%) of these five patients were discharged without the need for surgical
      intervention. The median hospital stay was 7.5 days. Seven patients required
      surgery overall with a median length of hospital stay of 10.8 days. Surgical
      procedures consisted of segmental bowel resection and primary anastomosis in six
      patients and simple closure in one. There was no perioperative deaths. One
      patient required percutaneous drainage because of anastomotic leak, and one
      required reoperation owing to evisceration. DISCUSSION: Selected patients with
      PJD can be successfully managed with conservative approach, based on clinical and
      computed tomography findings.

PMID- 30211721
TI  - Clinical study of combined mirror and extracorporeal shock wave therapy on upper
      limb spasticity in poststroke patients.
AB  - Mirror therapy is a simple, inexpensive, and patient-oriented method that has
      been shown to reduce phantom sensations and pain caused by amputation and improve
      range of motion, speed, and accuracy of arm movement and function. Extracorporeal
      shock wave therapy (ESWT) is a new, reversible, and noninvasive method for the
      treatment of spasticity after stroke. To investigate the therapeutic effect of
      the combination of mirror and extracorporeal shock wave therapy on upper limb
      spasticity in poststroke patients. We randomly assigned 120 patients into four
      groups: A, B, C, and D. All groups received conventional rehabilitation training
      for 30 min per day, five times a week, for 4 weeks. Moreover, participants in
      groups A, B, and C also added mirror therapy, ESWT, and a combination of mirror
      and ESWT, respectively, for 20 min per day. Motor recovery and spasticity were
      measured using Fugl-Meyer assessment and modified Ashworth scale. The differences
      in the Fugl-Meyer assessment and modified Ashworth scale scores in group C were
      significantly greater than those of group D at all observed time points after
      treatment and were significantly greater than those of groups A and B (P<0.05),
      but no significant differences were observed between groups A and B until 12
      months. Upper extremity spasticity was improved by combined mirror and ESWT.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- 30211723
TI  - Differential Outcomes Among Immunosuppressed Patients With Merkel Cell Carcinoma:
      Impact of Immunosuppression Type on Cancer-specific and Overall Survival.
AB  - OBJECTIVES: Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine skin
      cancer with higher incidence among whites, elderly, and immunosuppressed
      patients. Although immunosuppressed MCC patients are at higher risk of recurrence
      and MCC-related death, it is unknown whether immunosuppression type is associated
      with differential outcomes. MATERIALS AND METHODS: We retrospectively evaluated
      89 nonmetastatic MCC patients with a diagnosis of chronic immunosuppression.
      Immunosuppression was categorized as chronic lymphocytic leukemia (31% of
      cohort), other hematologic malignancies (18%), solid organ transplant (21%),
      autoimmune disease (21%), and human immunodeficiency virus acquired deficiency
      syndrome (8%). Progression-free survival (PFS) and MCC-specific survival (MSS)
      were estimated with the cumulative incidence function. Overall survival (OS) was
      estimated by the Kaplan-Meier method. RESULTS: With a median follow-up of 52
      months, 53 deaths occurred (42 from MCC, 7 unknown, and 4 non-MCC). Two-year PFS,
      MSS, and OS were 30%, 55%, and 52%, respectively. Human immunodeficiency
      virus/acquired deficiency syndrome and solid organ transplant patients were
      diagnosed with MCC at a younger age (median 55 and 59 y, respectively) and with
      more advanced stage disease compared with other immunosuppressed subgroups. PFS
      did not significantly differ among the 5 immunosuppression subgroups (P=0.30),
      but significant differences were observed in MSS and OS (both P=0.01).
      Controlling for potential confounders for OS, including age and stage,
      immunosuppression type was still significantly associated with risk of death
      (P=0.01). CONCLUSIONS: Among immunosuppressed MCC patients, recurrent MCC is the
      major cause of mortality. The risk of death from MCC differs among
      immunosuppression types, suggesting important biological differences in host
      tumor immune interactions.

PMID- 30211724
TI  - Comparison of Clinical Characteristics and Outcomes in Relapsed Versus De Novo
      Metastatic Non-Small Cell Lung Cancer.
AB  - OBJECTIVES: To compare the clinical characteristics and outcomes between relapsed
      and de novo metastatic non-small cell lung cancer (NSCLC). MATERIALS AND METHODS:
      We reviewed all NSCLC diagnoses between January 1999 and December 2013 in the
      institutional Glans-Look Lung Cancer Database, which contains demographic,
      clinical, pathologic, treatment, and outcome information. Patients with distant
      metastasis at diagnosis (American Joint Committee on Cancer [AJCC] eighth
      edition, stage IV), the "de novo" cohort, were compared with the "relapsed"
      cohort, consisting of patients diagnosed with early stage disease (stage I/II)
      undergoing curative intent treatment and subsequently experiencing metastatic
      relapse. Survival analysis, along with univariate and multivariable analysis was
      performed. RESULTS: A total of 185 relapsed and 3039 de novo patients were
      identified. Significantly different patterns of smoking history, histology,
      systemic therapy use, and disease extent were observed between the relapsed and
      de novo cohorts. Median overall survival from time of metastasis was
      significantly longer in relapsed than in de novo disease (8.9 vs. 3.7 mo,
      P<0.001). Relapsed patients demonstrated significant improvements in outcomes
      over time. In multivariate analysis, de novo metastatic disease continued to bode
      a worse prognosis (adjusted hazard ratio [HR], 1.4) as did male sex (HR, 1.2),
      never-smoking history (HR, 1.2), and presence of extrapulmonary metastases (HR,
      1.3). Systemic therapy receipt conferred better outcome (HR, 0.4), although the
      impact of relapsed versus de novo disease on outcomes persisted regardless of
      systemic therapy receipt. CONCLUSIONS: Relapsed and de novo patients represent
      significantly different subpopulations within metastatic NSCLC with the latter
      exhibiting poorer survival. This information facilitates discussions about
      prognosis with patients and supports screening initiatives aimed at reducing de
      novo disease.

PMID- 30211726
TI  - Cyclin D1-positive Mediastinal Large B-Cell Lymphoma With Copy Number Gains of
      CCND1 Gene: A Study of 3 Cases With Nonmediastinal Disease.
AB  - Primary mediastinal large B-cell lymphoma (PMBL) is a mature large B-cell
      lymphoma of putative thymic B-cell origin involving the mediastinum with younger
      age distribution and better prognosis than diffuse large B-cell lymphoma (DLBCL),
      not otherwise specified. Recently, based on gene expression profile analysis and
      morphologic findings, cases of PMBL without mediastinal involvement have been
      reported. In this study, we analyzed 3 cases of nodal DLBCL with morphologic
      features of PMBL presenting in submandibular or supraclavicular lymph nodes, in
      middle-aged to elderly patients, 2 of them without clinical or radiologic
      evidence of mediastinal involvement. The 3 patients presented with stage I/II
      disease and had excellent response to R-CHOP/R-EPOCH therapy. The 3 cases showed
      MAL expression and were positive for CD23 and/or CD30. All 3 cases expressed
      cyclin D1 with copy number gains of CCND1 gene but without rearrangement. There
      was no rearrangement of CIITA or PDL1/PDL2. Reverse transcriptase-multiplex
      ligation-dependent probe amplification, a mRNA-based gene expression profile
      analysis revealed high probability of PMBL (87.6%, 98.7%, and 99%) in these 3
      cases. Targeted next-generation sequencing analysis showed SOCS1 mutations in the
      3 cases, and TNFAIP3 and XPO1 mutations in one, further supporting the diagnosis
      of PMBL. In conclusion, we report 3 cases of nodal PMBL, 2 of them without
      mediastinal mass, and expression of cyclin D1 due to copy number gains of CCND1
      gene, a diagnostic pitfall with mantle cell lymphoma and DLBCL, not otherwise
      specified.

PMID- 30211725
TI  - Short- and long-term impact of remifentanil on thermal detection and pain
      thresholds after cardiac surgery: A randomised controlled trial.
AB  - BACKGROUND: The clinical relevance of the suggested hyperalgesic effects of
      remifentanil is still unclear, especially in the long term. OBJECTIVE: The
      current study evaluated the impact of remifentanil on thermal thresholds 3 days
      and 12 months after surgery, measured with Quantitative Sensory Testing. DESIGN:
      A single-blind, randomised controlled trial. SETTING: A tertiary care teaching
      hospital in The Netherlands, from 2014 to 2016. PATIENTS: A total of 126 patients
      aged between 18 and 85 years, undergoing cardiothoracic surgery via sternotomy
      (coronary artery bypass grafts and/or valve replacement) were included. Exclusion
      criteria were BMI above 35 kg m, history of cardiac surgery, chronic pain
      conditions, neurological conditions, allergy to opioids or paracetamol, language
      barrier and pregnancy. INTERVENTIONS: Patients were allocated randomly to receive
      intra-operatively either a continuous remifentanil infusion or intermittent intra
      operative fentanyl as needed in addition to standardised anaesthesia with
      propofol and intermittent intravenous fentanyl at predetermined time points. MAIN
      OUTCOME MEASURES: Warm and cold detection and pain thresholds 3 days and 12
      months after surgery. In addition the use of remifentanil, presence of
      postoperative chronic pain, age, opioid consumption and pre-operative quality of
      life were tested as a predictor for altered pain sensitivity 12 months after
      surgery. RESULTS: Both warm and cold detection, and pain thresholds, were not
      significantly different between the remifentanil and fentanyl groups 3 days and
      12 months after surgery (P > 0.05). No significant predictors for altered pain
      sensitivity were identified. CONCLUSION: Earlier reports of increased pain
      sensitivity 1 year after the use of remifentanil could not be confirmed in this
      randomised study using Quantitative Sensory Testing. This indicates that
      remifentanil plays a minor role in the development of chronic thoracic pain.
      Still, the relatively high incidence of chronic thoracic pain and its
      accompanying impact on quality of life remain challenging problems. TRIAL
      REGISTRATION: The study was registered at EudraCT (ref: 2013-000201-23) and
      ClinicalTrials.gov (https://clinicaltrials.gov/ct2/show/NCT02031016).

PMID- 30211722
TI  - Reduced Cancer Survival Among Adults With HIV and AIDS-Defining Illnesses Despite
      No Difference in Cancer Stage at Diagnosis.
AB  - BACKGROUND: It is not known whether immune dysfunction is associated with
      increased risk of death after cancer diagnosis in persons with HIV (PWH). AIDS
      defining illness (ADI) can signal significant immunosuppression. Our objective
      was to determine differences in cancer stage and mortality rates in PWH with and
      without history of ADI. METHODS: PWH with anal, oropharynx, cervical, lung
      cancers, or Hodgkin lymphoma diagnoses from January 2000 to December 2009 in the
      North American AIDS Cohort Collaboration on Research and Design were included.
      RESULTS: Among 81,865 PWH, 814 had diagnoses included in the study; 341 (39%) had
      a history of ADI at time of cancer diagnosis. For each cancer type, stage at
      diagnosis did not differ by ADI (P > 0.05). Mortality and survival estimates for
      cervical cancer were limited by n = 5 diagnoses. Adjusted mortality rate ratios
      showed a 30%-70% increase in mortality among those with ADI for all cancer
      diagnoses, although only lung cancer was statistically significant. Survival
      after lung cancer diagnosis was poorer in PWH with ADI vs. without (P = 0.0001);
      the probability of survival was also poorer in those with ADI at, or before other
      cancers although not statistically significant. CONCLUSIONS: PWH with a history
      of ADI at lung cancer diagnosis had higher mortality and poorer survival after
      diagnosis compared to those without. Although not statistically significant, the
      findings of increased mortality and decreased survival among those with ADI (vs.
      without) were consistent for all other cancers, suggesting the need for further
      investigations into the role of HIV-related immune suppression and cancer
      outcomes.

PMID- 30211727
TI  - "Fat-rich" (Spindle Cell-poor) Variants of Atypical Spindle Cell Lipomatous
      Tumors Show Similar Morphologic, Immunohistochemical and Molecular Features as
      "Dysplastic Lipomas": Are They Related Lesions? Comment on Michal et al (2018).

PMID- 30211728
TI  - Comparison of Tumor Regression Grading of Residual Pancreatic Ductal
      Adenocarcinoma Following Neoadjuvant Chemotherapy Without Radiation: Would Fewer
      Tier-Stratification Be Favorable Toward Standardization?
AB  - To assess whether the College of American Pathologists (CAP) and the Evans
      grading systems for neoadjuvant chemotherapy without radiation-treated
      pancreatectomy specimens are prognostic, and if a 3-tier stratification scheme
      preserves data granularity. Conducted retrospective review of 32 patients with
      ordinary pancreatic ductal adenocarcinoma treated with neoadjuvant therapy
      without radiation followed by surgical resection. Final pathologic tumor category
      (AJCC eighth edition) was 46.9% ypT1, 34.4% ypT2, and 18.7% ypT3. Median follow
      up time was 29.8 months, median disease-free survival (DFS) was 19.6 months, and
      median overall survival (OS) was 34.2 months. CAP score 1, 2, 3 were present in 5
      (15.6%), 18 (56.3%), and 9 (28.1%) patients, respectively. Evans grade III, IIb,
      IIa, and I were present in 10 (31.2%), 8 (25.0%), 7 (21.9%), and 7 (21.9%)
      patients, respectively. OS (CAP: P=0.005; Evans: P=0.001) and DFS (CAP: P=0.003;
      Evans: P=0.04) were statistically significant for both CAP and Evans. Stratified
      CAP scores 1 and 2 versus CAP score 3 was statistically significant for both OS
      (P=0.002) and DFS (P=0.002). Stratified Evans grades I, IIa, and IIb versus Evans
      grade III was statistically significant for both OS (P=0.04) and DFS (P=0.02).
      CAP, Evans, and 3-tier stratification are prognostic of OS and DFS.

PMID- 30211729
TI  - Atypical Varicella-Zoster Kaposi Varicelliform Eruption in Sezary Syndrome.
AB  - Patients with mycosis fungoides experience considerable morbidity and mortality
      from secondary bacterial and viral infections. Staphylococcus aureus, beta
      hemolytic streptococci, herpes simplex virus, and herpes zoster virus remain the
      most common infectious pathogens in this group of patients. With depressed
      cellular immunity and diminished skin barrier as the main precipitating risk
      factors, immunocompromised patients can often present with an atypical
      presentation of a common dermatologic condition. The case herein discusses a
      clinically atypical nonvesicular Kaposi varicelliform eruption secondary to a
      varicella-zoster virus in a patient with Sezary syndrome. Concurrent polypharmacy
      in these patients is also a risk factor for development of drug hypersensitivity
      reactions. However, given their immunocompromised status, first and foremost, a
      careful inspection should be made of every atypical skin eruption in search of an
      infectious etiology, and afterward, an appropriate treatment should be promptly
      initiated.

PMID- 30211730
TI  - Utility of TERT Promoter Mutations for Cutaneous Primary Melanoma Diagnosis.
AB  - Telomerase reverse transcriptase (TERT) promoter mutations are commonly found in
      malignant melanomas but rare in melanocytic nevi. To assess its potential
      diagnostic utility for the distinction of melanoma from nevus, we determined the
      TERT promoter mutation status of 86 primary melanomas, 72 melanocytic nevi, and
      40 diagnostically problematic melanocytic proliferations. Of the 86 melanomas, 67
      (77.9%) were TERT-positive, defined as harboring a hotspot TERT promoter mutation
      at positions -124C>T, -124_125CC>TT, -138_139CC>TT, or -146C>T. Of the 72 nevi,
      only 1 (1.4%) was TERT-positive. Of the 40 diagnostically uncertain melanocytic
      proliferations, 2 (5.0%) were TERT-positive. TERT positivity as a test for
      melanoma versus nevus had an accuracy of 87.3% [95% confidence interval (CI),
      81.1-92.1], a sensitivity of 77.9% (95% CI, 68.9-85.4), a specificity of 98.6%
      (95% CI, 95.8-100), a positive predictive value of 98.5% (95% CI, 95.6-100), and
      a negative predictive value of 78.9% (95% CI, 72.6-85.4). Our results indicate
      that hotspot TERT promoter mutation status may be a useful ancillary parameter
      for the diagnosis of melanoma. In particular, the high specificity of these
      mutations for melanoma indicates the presence of a TERT promoter mutation in a
      melanocytic neoplasm associated with diagnostic controversy, or uncertainty
      should increase concern for a melanoma.

PMID- 30211731
TI  - Facial Phaeohyphomycosis in an Immunocompetent Individual: A Rare Presentation of
      a Rare Fungus.
AB  - Phaeohyphomycosis is a rare mycotic infection caused by heterogenous groups of
      dematiaceous fungi involving the skin and subcutaneous tissue. Here, we report a
      case of cutaneous phaeohyphomycosis presenting as cauliflower-like verrucous
      lesion over the face in an immunocompetent individual. Histopathology showed
      suppurative granulomatous inflammation replete with pigmented broad fungal hyphae
      which is stained with periodic acid-Schiff stain, Grocott's methanamine silver
      stain, Schmorl's stain, and Masson-Fontana stain. Culture showed black-colored
      colonies identified as Exophiala spinifera.

PMID- 30211732
TI  - Pigmented Facial Contact Dermatitis to Benzyl Salicylate: A Comparative
      Histopathological and Immunohistochemical Study of the Involved Skin and the
      Positive Patch Test Site.
AB  - Pigmented contact dermatitis (PCD) is a noneczematous variant of allergic contact
      dermatitis, and benzyl salicylate is one of its causes. This type of PCD shows
      nonlichenoid interface dermatitis with pigment incontinence. We aimed to
      characterize the earliest histopathological changes of this reaction. A 51-year
      old man presented with persistent facial eruption composed of hyperpigmented and
      hypopigmented macules due to exposure to benzyl salicylate present in his
      aftershave. The biopsies obtained from hyperpigmented and hypopigmented macules,
      and from the positive patch test site to benzyl salicylate, showed a nonlichenoid
      focal vacuolar interface dermatitis with mononuclear cells in the papillary
      dermis and around the pilosebaceous units, along with melanophages. A MART-1
      immunostain showed intact melanocytes in all 3 biopsies. A Fontana-Masson stain
      demonstrated intact melanin in the basal cell layer of a facial hyperpigmented
      macule and the patch test site, but melanin was reduced in the biopsy taken from
      a hypopigmented facial macule. There were more epidermal and dermal CD1a+
      Langerhans cells in the patch test biopsy than in the other 2 biopsies. Most of
      the mononuclear cells were CD3+. The CD4+ to CD8+ ratio was approximately 1:1 in
      the facial macules; yet, CD4+ cells outnumbered CD8+ cells in the patch test
      biopsy. There were a few TIA-1+ cells in all 3 biopsies. In conclusion, the
      earliest histopathological and immunophenotypical events in PCD due to benzyl
      salicylate are similar to those of longer-standing lesions, i.e., a nonlichenoid
      focal interface dermatitis involving the epidermis and pilosebaceous unit, along
      with dermal melanophages.

PMID- 30211733
TI  - Borderline Lepromatous Leprosy: Uncommon Clinical Presentation.

PMID- 30211734
TI  - Histopathology of Hand-Foot-Mouth Disease in Adults and Criteria for
      Differentiation From Erythema Multiforme.
AB  - BACKGROUND: Hand-foot-mouth disease (HFMD) is a common contagious viral infection
      usually affecting infants and children. Recently, literature on HFMD in adults is
      increasing. It has been reported that adults often present with unusual exanthems
      with similarities to erythema multiforme (EM). No study has so far compared the
      histologic features of HFMD with those of EM. METHODS: Histopathologic features
      in 7 biopsies of 6 adult patients with HFMD are compared with biopsies from 9
      patients with EM to identify the best criteria for differentiation. RESULTS: HFMD
      and EM both have a perivascular lymphocytic infiltrate together with epidermal
      necrosis, spongiosis, ballooning, and reticular alteration. However, large
      numbers of neutrophils in parakeratosis (P < 0.05), in the viable epidermis (P <
      001), or neutrophils forming intraepidermal collections (P < 0.05) are
      significantly more common in HFMD. In HFMD, necrotic keratinocytes are emphasized
      in the upper third of the epidermis (P < 0.05), whereas the lower third is
      typically involved more in EM. Neutrophils are significantly more common and more
      numerous in the dermal infiltrate of HFMD compared with EM (P < 0.01)
      Extravasated erythrocytes in the epidermis are more common and more numerous in
      HFMD (P < 0.05). CONCLUSIONS: Lesions of EM and HFMD can be differentiated based
      on the amount of neutrophils in the epidermis and in the dermal infiltrate, which
      are significantly more numerous in HFMD. In addition, necrosis is emphasized in
      the upper part of the epidermis in HFMD and in the lower part of it in EM.

PMID- 30211735
TI  - Acute Retinal Necrosis Presenting With Optic Disc Edema.

PMID- 30211736
TI  - Two Cases of Radial Ray Deficiency With Absence of First Metacarpus and 2 Tiny
      Fingers.
AB  - We report 2 cases showing both radial ray deficiency and thumb duplication. The
      common features of these cases were absence of the first metacarpus and presence
      of 2 tiny fingers. The features of our cases may have been due to continuous
      abnormality of the mesenchymal cells before limb bud formation and apical
      ectodermal ridge at the established limb bud. In 1 case, we created a 5-finger
      hand using 2 tiny floating fingers. Two fingers as vascularized bones with growth
      potential were useful to make 1 thumb. Two tendon transfers at 2 years of age
      were effective to allow gripping and pinching of objects. At 6 years of age, the
      thumb was lengthened by an iliac bone graft and a reverse forearm flap. At 27
      years of age, the patient showed grip power of 20 kg in the affected hand. The
      Quick-DASH (the Japanese Society for Surgery of the Hand version) score was 4.6.
      The patient was satisfied with the appearance and function of the hand, although
      size discrepancy between the thumbs remained.

PMID- 30211737
TI  - Making Augmented and Virtual Reality Work for the Plastic Surgeon.
AB  - Augmented and virtual reality is an evolving technology at the forefront of
      medicine. It can provide physicians with hands-free, real-time access to the vast
      resources of the Internet and electronic medical records, allowing simultaneously
      recording of clinical encounters or procedures. Mixed reality platforms can be
      applied as a clinical tool, educational resource, or as an aid in enhancing
      communication in health care. This article will explore how various augmented and
      virtual reality platforms have enabled real-time visualization of patient
      information, recording of surgical cases, point-of-view photography, and
      intraoperative consults-all while remaining sterile in the operating room.
      Although this technology is of potential value to a number of different surgical
      and medical specialties, plastic surgery is ideally suited to lead this charge.

PMID- 30211738
TI  - Time to Radiation After Oncoplastic Reduction.
AB  - BACKGROUND: Partial breast reconstruction with reduction mammaplasty is an
      accepted option for women with breast cancer who wish to receive breast
      conserving therapy. With additional surgery and potential postoperative
      complications, the impact this approach has on the timely initiation of adjuvant
      radiation therapy has been raised as a concern. The purpose of this study was to
      determine if any postoperative complications after oncoplastic reduction (OCR)
      are associated with a delay in time to radiation. METHODS: All patients
      undergoing OCR with postoperative adjuvant radiation at a single institution
      between 1997 and 2015 were included in the analysis. Women who received adjuvant
      chemotherapy or experienced delays in radiation therapy due to nonsurgical
      reasons were excluded from our analysis. Comparisons were made between the time
      to radiation for patients with surgical complications and those without. RESULTS:
      One hundred eighteen patients were included. Twenty-six (22.0%) experienced a
      surgical complication. Complications included cellulitis, delayed healing,
      seroma, wound breakdown, and wound dehiscence. Postoperative complications
      resulted in a significantly different median time interval for initiation of
      radiation (74 days vs 54 days, P < 0.001) compared to those without a
      complication. Among the entire cohort, 5% of patients required a second operative
      procedure due to complications. (n = 6/118 patients) including hematoma,
      infection, seroma, open wounds, wound dehiscence, and nipple necrosis. There was
      no difference in median time to radiation therapy in those with complications who
      returned to the operating room (73 days) compared to those who did not (74 days,
      P = 0.692). CONCLUSION: Postoperative complications following OCR procedures were
      associated with an increased time to initiation of adjuvant radiation therapy
      regardless of whether or not the complication required reoperation. This needs to
      be taken into consideration when planning these combined procedures with every
      attempt made to minimize complications through patient selection and surgical
      technique.

PMID- 30211739
TI  - Venous Congestion in Pedicled Frontal Branch Superficial Temporal Artery Flaps
      Reconstructions for Head and Neck Defects: A Review.
AB  - The superficial temporal artery (STA) flap is a versatile flap for head and neck
      defect reconstruction. It can be based on the frontal branch of the STA and an
      islanded 360-degree rotation arc for various defects on the scalp, cheek, and
      auricular region. It provides a nonmicrosurgical option for reconstructing such
      defects, which is itself relatively easy to perform. However, venous congestion
      is a problem than often can cause worry to the clinician and hence preclude its
      use. In this review, we revisit this flap in head and neck reconstruction, with
      case examples used for reconstruction of defects on the scalp, maxilla, lip, ear,
      and retroauricular area. The STA flap in our review can be used either as a
      fasciocutaneous flap or with its fascia alone. The main issue with the STA flap
      is that it is generally a high-inflow flap with variable outflow. Venous
      congestion is frequently encountered in our practice, and adequate management of
      the venous drainage in the postoperative period is crucial in ensuring its
      success as a versatile and viable option for head and neck reconstruction.

PMID- 30211740
TI  - Defining a New Variable That May Impact Long-term Postoperative Nasal Tip
      Support: The Biomechanical Properties of the Columellar Strut Graft.
AB  - BACKGROUND: Although columellar strut grafts (CSGs) are considered among the
      fundamental steps for providing nasal tip support, a downward rotation of the
      nasal tip in patients with strut grafts can still be encountered. Patient-related
      factors such as nasal skin thickness can allow the plastic surgeon to anticipate
      certain drawbacks that can be encountered in the healing phase, but patient-based
      differences of nasal cartilage and the resulting impact have yet to be
      investigated. The purpose of this study was to evaluate the effect of the
      biomechanical properties of CSGs on late postoperative nasal tip position and
      support. METHODS: The study was undertaken with the participation of 20 patients
      undergoing closed-technique primary rhinoplasty with CSGs. Each cartilage
      specimen was biomechanically analyzed to calculate the modulus of elasticity.
      Preoperative and postoperative images were obtained to determine nasal tip
      position and rotation with quantitative measurements. Postoperative 3- and 12
      month measurements were evaluated according to their relationship with the
      elasticity modulus of the utilized cartilages. RESULTS: The evaluation
      demonstrated that the elasticity modulus can impact the long-term support of the
      nasolabial angle in which an increase in the coefficient of elasticity can result
      in a decrease in long-term nasal tip support. CONCLUSION: The results of the
      study reveal a new objective variable that can impact nasal tip dynamics and
      patient-related differences following rhinoplasty. This study not only brings
      forth a different perspective in the evaluation of nasal tip dynamics but can
      also provide data for determining ideal values for cartilage prefabrication.

PMID- 30211741
TI  - Effect of Posthospital Syndrome on Health Care Utilization After Abdominal
      Contouring Surgery.
AB  - BACKGROUND: Posthospital syndrome (PHS) is a transient condition after acute
      hospitalizations when patients are physiologically deconditioned. The objective
      of this study was to determine if having PHS at the time of abdominal contouring
      surgery increased the incidence of postoperative adverse medical events. METHODS:
      We conducted a retrospective cohort study of patients enrolled in the MarketScan
      Databases who underwent outpatient functional or cosmetic abdominal contouring
      surgery (ie, abdominoplasty, liposuction, or panniculectomy) from April 2010 to
      August 2015. Patients were separated into 2 groups based upon PHS exposure,
      defined by hospitalization within 90 days before surgery. Differential health
      care utilization within 30 days after surgery was compared between cohorts.
      RESULTS: Among the 18,947 patients included in the final cohort, 1045 patients
      (6%) had PHS at the time of abdominal contouring surgery. Patients with PHS
      experienced more emergency department visits (0.16 vs 0.08 visits; adjusted odds
      ratio, 1.60; P < 0.001) and more episodes of hospitalization (0.11 vs 0.04
      episodes; adjusted odds ratio, 1.70; P < 0.001) within 30 days postoperatively.
      The mean unadjusted health care utilization after abdominal contouring surgery
      for patients with PHS was US $7888 (SD, 17,659) versus US $2943 (SD, 9096) in
      patients without PHS. After controlling for confounders, such as comorbidity
      burden, PHS was associated with US $3944 greater cost than patients without PHS
      (P < 0.001). CONCLUSIONS: Among patients undergoing outpatient abdominal
      contouring surgery, having PHS increased the incidence of adverse medical events
      requiring medical attention in the 30-day postoperative period. These findings
      support the inclusion of PHS in preoperative evaluation and preparation for
      patients seeking abdominal contouring surgery.

PMID- 30211742
TI  - Appropriate Sequence of Combined Intracorneal Ring Implantation and Corneal
      Collagen Cross-Linking in Keratoconus: A Systematic Review and Meta-Analysis.
AB  - PURPOSE: To compare surgical sequences of combined intracorneal ring segment
      (ICRS) implantation and corneal collagen cross-linking (CXL) in keratoconus and
      corneal ectasia in terms of visual, refractive, and keratometric outcomes.
      METHODS: A comprehensive electronic search (in PubMed, Web of Science, Scopus,
      Embase, and Cochrane Library) was conducted in accordance with the PRISMA
      statement to find articles on combined ICRS implantation and CXL in keratoconus
      and corneal ectasia. The search period was from the inception of the database up
      to April 2017. Eligible articles were categorized into 3 surgical sequences (same
      day, ICRS first, and CXL first) and assessed qualitatively. Articles with 12
      months of follow-up data after combined surgery were included in the meta
      analysis. RESULTS: The initial search identified 120 related articles, of which
      17 were included in the review after screening. The quality assessment showed
      that visual, refractive, and keratometric improvement was observed in all studies
      in all 3 groups of combined surgery. Meta-analysis on 6 studies that reported 12
      month follow-up outcomes showed no significant differences between the 3 groups
      regarding uncorrected and best-corrected visual acuity and cylindrical refractive
      error. However, results with simultaneous surgery were superior to the CXL-first
      technique in terms of spherical refractive errors and flat-K (P = 0.011 and P =
      0.0001, respectively) and to both CXL first and ICRS first in terms of steep-K (P
      = 0.002 and P = 0.007, respectively). CONCLUSIONS: Simultaneous ICRS implantation
      and CXL may provide better outcomes than staged techniques for improving the
      corneal shape.

PMID- 30211744
TI  - Evaluation of Corneal Epithelial Thickness Imaged by High Definition Optical
      Coherence Tomography in Healthy Eyes.
AB  - PURPOSE: To evaluate corneal epithelial thickness (CET) and corneal thickness
      (CT) in healthy eyes using spectral domain optical coherence tomography. METHODS:
      Thirty-six healthy eyes were imaged using the Cirrus high-definition (HD)-optical
      coherence tomography device. The average CET and CT were assessed using Cirrus
      Review Software within predefined concentric corneal ring-shaped zones. Specific
      regions of CET (superior, inferior, temporal, nasal, superonasal, inferotemporal,
      superotemporal, and inferonasal) were also assessed. The difference between zones
      was compared between males and females. RESULTS: The average CET was 48.3, 47.1,
      46.1, and 45.8 MUm in the 4 concentric zones (0-2, 2-5, 5-7, and 7-9 mm),
      respectively (P < 0.001). The average CT was 533.5, 550.8, and 579.4 MUm in the 3
      zones (0-2, 2-5, and 5-7 mm), respectively (P < 0.001). There was no
      statistically significant correlation between CET and CT in any of the measured
      zones. Males had thicker corneas than did females in each of the 3 CT zones (P <
      0.05), but CET did not differ significantly. The CET superonasal-inferotemporal
      in 2.0 to 5.0 mm and CET superotemporal-inferonasal in 5.0- to 7.0-mm zones were
      significantly thinner in males than in females (-1.15 vs. 0.9 MUm, -3.5 vs. -1.9
      MUm), respectively (P < 0.05). CONCLUSIONS: Optical coherence tomography-based
      analysis of CET reveals that it is thinner in the periphery, whereas the total
      corneal thickness is greater. Although total CT seems to be influenced by sex,
      CET is not. Regional and sex-based variations in CT may need to be considered
      when assessing corneal and epithelial alterations in the setting of disease.

PMID- 30211743
TI  - Epidemiology of Persistent Postsurgical Pain Manifesting as Dry Eye-Like Symptoms
      After Cataract Surgery.
AB  - PURPOSE: To evaluate the epidemiology of persistent postsurgical pain (PPP)
      manifesting as dry eye (DE)-like symptoms 6 months after surgery. METHODS: This
      single-center study included 119 individuals whose cataract surgeries were
      performed by a single surgeon at the Bascom Palmer Eye Institute and who agreed
      to participate in a phone survey 6 months after surgery. Patients were divided
      into 2 groups: the PPP group was defined as those with a Dry Eye Questionnaire-5
      score >=6 and without PPP as those with a Dry Eye Questionnaire-5 score <6 at 6
      months after cataract surgery. RESULTS: Mean age of the study population was 73
      +/- 8.0 years; 55% (n = 66) were female. PPP was present in 34% (n = 41) of
      individuals 6 months after surgery. Factors associated with an increased risk of
      PPP were female sex [odds ratio (OR) = 2.68, 95% confidence interval (CI) = 1.20
      6.00, P = 0.01], autoimmune disorder (OR = 13.2, CI = 1.53-114, P = 0.007),
      nonocular chronic pain disorder (OR = 4.29, CI = 1.01-18.1, P = 0.06),
      antihistamine use (OR = 6.22, CI = 2.17-17.8, P = 0.0003), antireflux medication
      use (OR = 2.42, CI = 1.04-5.66, P = 0.04), antidepressant use (OR = 3.17, CI =
      1.31-7.68, P = 0.01), anxiolytic use (OR = 3.38, CI = 1.11-10.3, P = 0.03), and
      antiinsomnia medication use (OR = 5.28, CI = 0.98-28.5, P = 0.047). PPP patients
      also reported more frequent use of artificial tears (P < 0.0001), higher ocular
      pain levels (P < 0.0001), and greater neuropathic ocular pain symptoms, including
      burning (P = 0.001), wind sensitivity (P = 0.001), and light sensitivity (P <
      0.0001). CONCLUSIONS: PPP in the form of persistent DE-like symptoms is present
      in approximately 34% of individuals 6 months after cataract surgery. The
      frequency of PPP after cataract surgery is comparable to that of other surgeries
      including laser refractive surgery, dental implants, and genitourinary
      procedures.

PMID- 30211746
TI  - Innovative Development of Contact Lenses.
AB  - Contact lenses have been a common means of vision correction for more than half a
      century. Recent developments have raised the possibility that the next few
      decades will see a considerable broadening of the range of applications for
      contact lenses, with associated expansions in the number and type of individuals
      who consider them a valuable option. The novel applications of contact lenses
      include treatment platforms for myopic progression, biosensors, and ocular drug
      delivery. Orthokeratology has shown the most consistent treatment for myopia
      control with the least side effects. Recent work has resulted in
      commercialization of a device to monitor intraocular pressure for up to 24 hours,
      and extensive efforts are underway to develop a contact lens sensor capable of
      continuous glucose tear film monitoring for the management of diabetes. Other
      studies on drug-eluting contact lenses have focused on increasing the release
      duration through molecular imprinting, use of vitamin E, and increased drug
      binding to polymers by sandwiching a poly (lactic-co-glycolic acid) layer in the
      lens. This review demonstrates the potential for contact lenses to provide novel
      opportunities for refractive management, diagnosis, and management of diseases.

PMID- 30211745
TI  - Fenretinide Inhibits Neutrophil Recruitment and IL-1beta Production in
      Aspergillus fumigatus Keratitis.
AB  - PURPOSE: Fungal keratitis is a major cause of corneal ulcers, resulting in
      significant visual impairment and blindness. Fenretinide, a derivative of vitamin
      A, has been shown to suppress inflammation in a multitude of diseases. In this
      study, we aimed to characterize the effect of fenretinide in Aspergillus
      fumigatus keratitis of the eye in a mouse model. METHODS: In vivo and in vitro
      experiments were performed in mouse models and THP-1 macrophage cell cultures
      infected with A. fumigatus, respectively. Experimental subjects were first
      pretreated with fenretinide, and then the effect of the compound was assessed
      with clinical evaluation, neutrophil staining, myeloperoxidase assay,
      quantitative polymerase chain reaction (qRT-PCR), and western blot. RESULTS: We
      confirmed that fenretinide contributed to protection of corneal transparency
      during early mouse A. fumigatus keratitis by reducing neutrophil recruitment,
      decreasing myeloperoxidase (MPO) levels and increasing apoptosis. Compared with
      controls, fenretinide impaired proinflammatory cytokine interleukin 1 beta (IL
      1beta) production in response to A. fumigatus exposure with contributions by
      lectin-type oxidized LDL receptor 1 (LOX-1) and c-Jun N-terminal kinase (JNK).
      CONCLUSIONS: Together, these findings demonstrate that fenretinide may suppress
      inflammation through reduced neutrophil recruitment and inflammatory cytokine
      production in A. fumigatus keratitis.

PMID- 30211747
TI  - Implications of Inflammasomes in Human Diseases: NLRP3 Inflammasome and Animal
      Models.
AB  - Danger-associated molecular patterns, such as nuclear or cytosolic proteins
      released outside the cell or exposed on the cell surface after tissue injury, and
      pathogen-associated molecular patterns, such as lipopolysaccharide,
      peptidoglycan, and nucleic acid, stimulate the formation of a large protein
      complex called the inflammasome. The inflammasome is a cytosolic complex of 3
      proteins that cleaves and releases interleukin-1beta. Recent studies have
      characterized a multitude of inflammasome ligands of both endogenous and
      exogenous origins. Moreover, using various animal models, the implications of
      inflammasomes in human diseases have been elucidated for multifaceted diseases
      such as metabolic syndrome, inflammatory bowel disease, Alzheimer disease, and
      certain inflammatory skin diseases. This article reviews several of these
      conditions and discusses the different models proposed for inflammasome
      involvement, including animal models of the cornea.

PMID- 30211748
TI  - What Have We Learned From the Osaka Study?
AB  - PURPOSE: To summarize the results of a cross-sectional epidemiologic study of
      Japanese office workers who use visual display terminals (VDTs). METHODS: Workers
      in a pharmaceutical company head office were recruited. Participants were
      requested to complete a questionnaire on symptoms of dry eye disease (DED) and
      evaluations using the Work Limitations Questionnaire, International Physical
      Activity Questionnaire, Subjective Happiness Scale, and Pittsburgh Sleep Quality
      Index. Evaluations of ocular status, including conjunctival and corneal vital
      staining with lissamine green and fluorescein, measurement of tear film breakup
      time, and the Schirmer test, were performed. The Japanese 2007 diagnostic
      criteria for DED were implemented. RESULTS: The prevalence of DED among VDT
      workers was high. Definite DED was present in 11.6% (18.7% women and 8.0% men) of
      participants, and probable DED was present in 54.0% (57.8% women and 52.1% men).
      Total loss of workplace productivity was significantly greater in the definite
      DED group (4.82%) than in the probable DED group (4.06%) and the non-DED group
      (3.56%, P < 0.014, trend test). Participants with definite DED had significantly
      lower physical activity scores than those without DED (P = 0.025). Subjective
      happiness correlated with the dry eye symptom score (r = -0.188; P < 0.001).
      Participants with DED reported poor sleep quality at a higher rate compared with
      those without DED (45% vs. 34%), with a significant difference in the global
      score (P = 0.002). CONCLUSIONS: Dry eye is prevalent among VDT workers. Its
      impacts on work productivity, physical activity, and sleep quality warrant
      further study.

PMID- 30211749
TI  - Ocular Surface Reconstruction with the Autologous Conjunctival Epithelium and
      Establishment of a Feeder-Free and Serum-Free Culture System.
AB  - Transplantation of the autologous cultured corneal limbal epithelium and oral
      mucosal epithelium is a standard technique for ocular surface reconstruction
      under corneal limbal stem cell deficiency. As an option for bilateral cases, we
      recommend utilization of autologous conjunctivae for ocular surface
      reconstruction. Autologous conjunctival epithelium sheet transplantation was
      effective for bilateral corneal limbal stem cell deficiency without symblepharon
      or severe keratinization. Moreover, we established a feeder-free and serum-free
      culture system of the limbal epithelium. This system can be applied for culturing
      conjunctival epithelia. Autologous cultured conjunctival epithelium
      transplantation is a practical option for treating bilateral corneal limbal stem
      cell deficiency.

PMID- 30211750
TI  - Development and Functional Modulation of Regulatory T Cells by Transcription
      Factors and Epigenetics.
AB  - Regulatory T cells (Tregs) are essential for the maintenance of immune
      homeostasis. Studies of Treg are not only necessary for understanding the
      mechanism of immune homeostasis but also extremely useful for the development of
      treatments of various immune diseases. Forkhead box P3 (Foxp3) was identified as
      the master gene responsible for the immune-suppressing activity of Tregs. The
      promoter region and several intronic enhancers, designated conserved noncoding
      sequence (CNS) 0, 1, 2, and 3, at the Foxp3 gene locus have important roles in
      Foxp3 expression and Treg development. We demonstrated that transcription factors
      Nr4a and Smad2/3 are required for development of thymic Tregs and induced Tregs,
      respectively. In addition to transcription factors, Treg-specific DNA
      demethylation has been shown to be important for Treg stability. In particular,
      DNA demethylation of CNS2 was implicated in Treg stability, and members of the
      ten-eleven translocation family of demethylation factors were recently
      demonstrated to have important roles in 5'-C-phosphate-G-3' demethylation at
      CNS2. This article summarizes recent findings regarding the roles of
      transcription factors and epigenetic modifications in the differentiation,
      maintenance, and function of Tregs. This review will facilitate clinical
      application of Tregs to diseases in the field of ophthalmology, including uveitis
      and age-related macular degeneration.

PMID- 30211751
TI  - Five Misconceptions Related to Punctal Plugs in Dry Eye Management.
AB  - Punctal plugs are an effective treatment option for patients with aqueous
      deficient dry eye refractory to topical medications. However, punctal plugs are
      not commonly used in clinical practice mainly because of various misconceptions,
      rather than clinical complications. We analyzed previous studies and present 5
      misconceptions related to punctal plugs. The first and most important
      misconception is that ocular surface inflammation should be sufficiently
      controlled before punctal plug insertion. However, it is unclear how ocular
      surface inflammation can be sufficiently controlled in patients refractory to
      conventional topical medications. The second misconception is that silicone
      punctal plugs are made of nonabsorbable materials and, therefore, permanent. In
      fact, silicone plugs are reversible and can be easily removed if necessary.
      Therefore, depending on the specific type, nonabsorbable plugs may be classified
      as reversible or permanent. The third misconception is that punctal plugs disrupt
      normal tear drainage. However, punctal plugs maintain natural tears on the ocular
      surface for extended periods and reduce the frequency of artificial tear use. The
      fourth is that all punctal and canalicular plugs have similar effects. The
      efficacy and complication rates differ depending on plug types. The fifth
      misconception about punctal plugs is that they are effective only in aqueous
      deficient dry eye disease. Many studies have reported that plugs are effective in
      a variety of ocular diseases and conditions. Understanding these 5 misconceptions
      may provide an opportunity to rethink the use of silicone punctal plugs in
      clinical practice.

PMID- 30211752
TI  - Assessing the Effectiveness of Using Mechanistic Concept Maps in Case-Based
      Collaborative Learning.
AB  - PROBLEM: Despite the advantages of using mechanistic concept maps (MCMs)-diagrams
      created individually or collaboratively by a team to foster inductive analysis of
      a clinical problem-in individual learning, very little is known about their
      benefits in collaborative learning. APPROACH: First-year medical and dental
      students (n = 170) were assigned to one of four learning groups in the
      Homeostasis I course, Harvard Medical School, February-March 2016. One group (n =
      43) was randomly assigned to the MCM intervention; students in the remaining
      groups (n = 127) served as controls. Outcomes included pre- and post-course
      surveys on, among other things, reasoning skills, attitudes toward teamwork, and
      tolerance of ambiguity; final exam scores; and qualitative responses to three
      open-ended questions on students' perceptions of the effects of MCMs on their
      learning. OUTCOMES: Response rates for pre- and post-course surveys were 87/170
      (51%) and 91/170 (54%). Compared with students in the control groups, students in
      the MCM group reported better reasoning skills (P = .01) and attitudes toward
      teamwork (P = .02). There were no significant differences in final exam scores
      between the groups. Students in the intervention group found MCMs more helpful in
      conceptual learning than their own notes and flashcards (P = .0001) or the
      readiness assessment quizzes (P = .0009). Qualitative analysis indicated that MCM
      students routinely overcame team-learning obstacles through strategies aimed at
      prioritizing collaborative inductive reasoning. NEXT STEPS: Ongoing studies are
      evaluating the contextual elements and best practices for optimal employment of
      MCMs in promoting collaborative inductive reasoning.

PMID- 30211753
TI  - Improving Employee Voice About Transgressive or Disruptive Behavior: A Case
      Study.
AB  - PURPOSE: Employee voice plays an important role in organizational intelligence
      about patient safety hazards and other influences on quality of patient care. The
      authors report a case study of an academic medical center that aimed to
      understand barriers to voice and make improvements in identifying and responding
      to transgressive or disruptive behaviors. METHOD: The case study focuses on an
      improvement effort at Johns Hopkins Medicine that sought to improve employee
      voice using a two-phase approach of diagnosis and intervention. Confidential
      interviews with 67 individuals (20 senior leaders, 47 frontline personnel) were
      conducted during 2014 to diagnose causes of employee reluctance to give voice
      about behavioral concerns. A structured intervention program to encourage voice
      was implemented, 2014-2016, in response to the findings. RESULTS: The diagnostic
      interviews identified gaps between espoused policies of encouraging employee
      voice and what happened in practice. A culture of fear pervaded the organization
      that, together with widespread perceptions of futility, inhibited personnel from
      speaking up about concerns. The intervention phase involved four actions: sharing
      the interview findings; coordinating and formalizing mechanisms for identifying
      and dealing with disruptive behavior; training leaders in encouraging voice; and
      building capacity for difficult conversations. CONCLUSIONS: The problems of
      giving voice are widely known across the organizational literature, but difficult
      to address. This case study offers an approach that includes diagnostic and
      intervention phases that may be helpful in remaking norms, facilitating employee
      voice, and improving organizational response. It highlights specific actions that
      are available for other organizations to adapt and test.This is an open access
      article distributed under the Creative Commons Attribution License 4.0 (CC-BY),
      which permits unrestricted use, distribution, and reproduction in any medium,
      provided the original work is properly cited.

PMID- 30211754
TI  - Overshadowed by Assessment: Understanding Trainee and Supervisor Perspectives on
      the Oral Case Presentation in Internal Medicine Workplace-Based Assessment.
AB  - PURPOSE: The oral case presentation (OCP) is an essential part of daily clinical
      practice in internal medicine (IM) and a key competency in medical education. It
      is not known how supervisors and trainees perceive OCPs in workplace-based
      learning and assessment. METHOD: Using a constructivist grounded theory approach,
      26 semistructured interviews were held with trainees and supervisors (18 clinical
      clerks and first- through third-year postgraduate trainees, and 8 supervisors) on
      the IM clinical teaching unit at the University of Toronto, 2015-2016. Interviews
      focused on how the OCP was viewed by both trainees and supervisors in clinical
      practice as a tool for patient care, learning, and assessment. Iterative,
      constant comparative techniques were used to analyze the interviews and develop a
      framework to understand trainee and supervisor perspectives. RESULTS: Supervisors
      and trainees viewed the OCP as an important part of informal trainee assessment
      in IM. Supervisors used OCPs to understand the patient, through trainee
      demonstrated skills including the use of narratives, information synthesis, and
      management of uncertainty. However, due to awareness of assessment, trainees
      sought to control the OCP: viewing it as a performance demonstrating their
      competence, mediated by senior residents and tailored to supervisor preferences.
      CONCLUSIONS: Preoccupied with assessment around OCPs, trainees often lost sight
      of the valuable learning taking place. Use of OCPs in assessment necessitates
      optimization of the educational activity for trainees. Providing explicit
      direction to both trainees and supervisors, defining expectations, and clarifying
      the assessment activity of the OCP can optimize the encounter for best
      educational practice.

PMID- 30211755
TI  - Moving the United States Medical Licensing Examination Step 1 After Core
      Clerkships: An Outcomes Analysis.
AB  - PURPOSE: Schools undergoing curricular reform are reconsidering the optimal
      timing of Step 1. This study provides a psychometric investigation of the impact
      on United States Medical Licensing Examination Step 1 scores of changing the
      timing of Step 1 from after completion of the basic science curricula to after
      core clerkships. METHOD: Data from four schools that recently moved the
      examination were analyzed in a pre-post format using examinee scores from three
      years before and after the change. The sample included scores from 2008 through
      2016. Several confounders were addressed, including rising national scores and
      potential differences in cohort abilities using deviation scores and analysis of
      covariance (ANCOVA) controlling for Medical College Admission Test (MCAT) scores.
      A resampling procedure compared study schools' score changes to similar schools'
      in the same time period. RESULTS: The ANCOVA indicated that post-change Step 1
      scores were higher compared to pre-change (adjusted difference = 2.67, 95%
      confidence interval [CI]: 1.50-3.83, P < .001; effect size = 0.14) after
      adjusting for MCAT scores and rising national averages. The average score
      increase in the study schools was larger than changes seen in similar schools.
      Failure rates also decreased from 2.87% (n = 48) pre-change to 0.39% (n = 6) post
      change (P < .001). CONCLUSIONS: Results suggest moving Step 1 after core
      clerkships yielded a small increase in scores and a reduction in failure rates.
      While these small increases are unlikely to represent meaningful knowledge gains,
      this demonstration of "non-inferiority" may allow schools to implement
      significant curricular reformsWritten work prepared by employees of the Federal
      Government as part of their official duties is, under the U.S. Copyright Act, a
      "work of the United States Government" for which copyright protection under Title
      17 of the United States Code is not available. As such, copyright does not extend
      to the contributions of employees of the Federal Government.

PMID- 30211756
TI  - 18F-Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography for the
      Diagnosis of Large Vessel Vasculitis Associated With Malignancy: A Case of Large
      Vessel Vasculitis Associated With Neuroendocrine Carcinoma of the Duodenum.

PMID- 30211757
TI  - Meteorological Factors and Air Pollutants Contributing to Seasonal Variation of
      Acute Exacerbation of Atrial Fibrillation: A Population-Based Study.
AB  - OBJECTIVE: We investigated seasonal variation of acute exacerbation of atrial
      fibrillation (AAF) and contributing environmental factors. METHODS: AAF events,
      meteorological elements, and air pollutants in Seoul between 2013 and 2015 were
      obtained from the nationwide database. AAF was defined if a patient visited the
      emergency room due to any AF-relevant symptoms or signs. RESULTS: AAF occurred
      less frequently in summer than in other seasons (6.71 vs. 7.25 events/day, p =
      0.005). AAF tended to decrease with an increase of air temperature (r = -0.058).
      Among air pollutants, NO2 was significantly lower in summer and positively
      correlated with AAF after adjusting for other variables (beta = 3.197).
      CONCLUSIONS: The rate of AAF events was the lowest in summer; air temperature and
      NO2 were contributing factors. The weather and environmental conditions should be
      considered as risk factors of AAF.

PMID- 30211758
TI  - Leukocyte Transcriptional Response in Sepsis.
AB  - BACKGROUND: The complex host response to sepsis is incompletely understood. The
      aim of this investigation is to use leukocyte RNA sequencing to characterize
      biological functions, cellular pathways, and key regulatory molecules driving
      sepsis pathophysiology. METHODS: This was a prospective, observational study of
      Emergency Department patients with sepsis, at an urban, academic, tertiary care
      center. In the derivation cohort, we collected blood at enrollment and 90 days
      after hospital discharge allowing each patient to serve as an internal control.
      We performed RNA sequencing to quantify transcriptional expression changes during
      sepsis and non-sepsis states. We then performed unsupervised and supervised
      analyses, as well as functional and pathway analyses. We selected the top down-
      and up- regulated genes and key regulatory molecules for validation. Validation
      occurred in a cohort of septic and non-septic using real-time PCR. RESULTS: The
      derivation cohort included 5 patients, and RNA sequencing revealed 916 unique
      mRNA transcripts differentially expressed during sepsis. Among these, 673 (73%)
      genes were up-regulated, and 243 (27%) were down-regulated. Functional enrichment
      analysis revealed a highly dynamic downstream effect of the transcriptional
      activity during sepsis. Of the 43 functional cellular pathways activated during
      sepsis, the top pathways were closely associated with inflammation and response
      to infection. Validation occurred in 18 septic and 25 non-septic control
      patients, with 34/45 (76%) of identified genes validated. The regulatory analysis
      identified several key regulators of sepsis. CONCLUSIONS: Highly dynamic
      transcriptional activity occurs in leukocytes during sepsis, activating key
      cellular pathways and master regulatory molecules that drive the sepsis process.

PMID- 30211759
TI  - Accuracy Comparison Between Age-Adapted Sofa and Sirs in Predicting In-Hospital
      Mortality of Infected Children at China's PICU.
AB  - OBJECTIVES: Sepsis-3 consensus suggests "the need to develop similar updated
      definitions for pediatric populations". Sequential organ failure assessment
      (SOFA) and systemic inflammatory response syndrome (SIRS) criteria are two
      systems widely used to define the status of infection. However, It is still
      unclear whether SOFA is more accurate than SIRS in predicting children mortality
      in low- and middle-income countries. Thus, we validated the accuracy of age
      adapted SOFA and SIRS in predicating the poor prognosis of infected children in
      China's pediatric intensive care unit (PICU). METHODS: We performed a
      retrospective and observational cohort study of children admitted for infection
      to PICU in the hospital between January 1, 2009 and December 31, 2017. The
      indexes within 24 hours after ICU admission were analyzed according to age
      adapted SOFA and SIRS, and all data were sourced from the hospital's electronic
      health record database. The prognosis was illustrated with primary outcome and
      secondary outcome. Primary outcome referred to in-hospital mortality, and
      secondary outcome to in-hospital mortality or ICU length of stay >= 7 days. The
      predictive power of age-adapted SOFA and SIRS was compared using crude and
      adjusted area under the receiver operating characteristic curve(AUROC). RESULTS:
      Of 1831 PICU-admitted children due to infection, 164 (9.0%) experienced primary
      outcome, and 948 (51.8%) secondary outcome. Of 164 deaths, 65.9% were males
      (median age of 7.53 m, range of 2.67-41.00 m). Children who scored >= 2 in age
      adapted SOFA or met two SIRS criteria accounted for 92.5% and 73.3%,
      respectively. In addition, age-adapted SOFA score of >=2 predicted adverse
      outcome more accurately than pediatric SIRS (adjusted AUROC, 0.753; 0.713-0.796
      vs. 0.674; 0.631-0.702; p < 0.001). CONCLUSIONS: Compared to SIRS criteria, age
      adapted SOFA score of >= 2 enjoys a more accuracy in predicting in-hospital
      mortality of PICU-admitted children, and a higher sensitivity in identifying
      children with severe infection.

PMID- 30211761
TI  - Creating the Framework for a Healthy Practice Environment.
AB  - The link between healthy work environments and patient safety, nursing
      satisfaction, and quality outcomes is well established, yet many nurses work in
      environments that are unsafe and uncivil. What are the essential elements that
      contribute to a healthy practice environment? How can we create roles and working
      conditions that enable nurses to be fulfilled and happy in their careers? This
      month's Magnet Perspectives column explores the relationship between a healthy
      practice environment and better outcomes and examines how the Journey to Magnet
      Excellence(r) leads to higher nurse satisfaction and retention, improved
      interdisciplinary collaboration, excellent patient care, and exemplary patient
      results.

PMID- 30211760
TI  - Evaluating competence and confidence using simulation technology.
AB  - This article discusses the role of simulation training in educating nurses and
      reducing clinical errors and describes a research project designed to determine
      the effectiveness of deliberate practice and simulation technology.

PMID- 30211762
TI  - Exploring Resilience at Work Among First-Line Nurse Managers.
AB  - OBJECTIVES: This study explored the assessment of resilience at work among 1st
      line nurse managers (NMs). BACKGROUND: Resilience is the ability to cope with
      stress. NMs have stressful roles and may ultimately withdraw from management if
      they lack resilient behaviors. Having a measurement of resilience at work in NMs
      and other healthcare workers may facilitate resilience development approaches.
      METHODS: In a descriptive, cross-sectional design, an electronic survey of 25
      item, 7-subscale Resilience at Work (RAW) self-report assessment was distributed
      to 77 NMs. RESULTS: The highest reported subscale was living authentically;
      lowest was maintaining perspective. Total years as NM was related to overall RAW
      mean, maintaining perspective, staying healthy. CONCLUSION: The application of an
      instrument to determine resilience may focus support for NMs on maintaining
      perspective, for example. Further study exploring the application of the RAW
      assessment to healthcare workers is indicated.

PMID- 30211763
TI  - Magnet(r) Culture and Leadership: Research and Empirical Outcomes.

PMID- 30211764
TI  - Leadership Practices and Engagement Among Magnet(r) Hospital Chief Nursing
      Officers.
AB  - OBJECTIVE: Describe the relationship between leadership practices and engagement
      of chief nursing officers (CNOs) in Magnet(r) organizations. BACKGROUND:
      Transformational leadership practices and CNO engagement are vital in influencing
      nursing practice. METHODS: Magnet hospital CNOs were invited to participate in a
      quantitative descriptive study via an online survey published in 2 newsletters.
      RESULTS: The CNOs rated their leadership practices high across all dimensions;
      the top leadership practice of Magnet CNOs was enabling others to act. There was
      a strong positive correlation between the vigor of engagement and the challenge
      the process leadership practice. CONCLUSION: This is the 1st study of Magnet CNOs
      transformational leadership practices and their work engagement and therefore
      adds to our understanding of the important characteristics to build future
      leadership development programs for nurse leaders at the executive level.
      Particularly noteworthy for the development of future nurse executives is the
      strong link between vigor and challenging the process.

PMID- 30211765
TI  - What Is New in Endometriosis?: Best Articles of the Past Year.
AB  - This month we focus on current research in endometriosis. Dr. Stovall discusses
      four recent publications, which are concluded with a "bottom-line" that is the
      take-home message. A complete reference for each can be found in on this page
      along with direct links to the abstracts.

PMID- 30211766
TI  - Noninferiority Complex.

PMID- 30211767
TI  - Connect the Dots-October 2018.

PMID- 30211768
TI  - A Dose of Forgiveness.

PMID- 30211769
TI  - Effectiveness of the Dual Dispatch to Cardiac Arrest Policy in Houston, Texas.
AB  - CONTEXT: Houston policy is to dual dispatch medically trained firefighters, in
      addition to emergency medical services (EMS) units to out-of-hospital cardiac
      arrest (OHCA) cases. While believed to improve public health outcomes, no
      research exists supporting the policy that when firefighters respond before a
      better-equipped EMS unit, they increase the probability of survival. OBJECTIVE:
      To inform EMS policy decisions regarding the effectiveness of dual dispatch by
      determining the impact of medically trained firefighter dispatch on return of
      spontaneous circulation (ROSC), a measure of survivability, in OHCA 911 calls
      while controlling for the subsequent arrival of an EMS unit. DESIGN: This
      retrospective study uses logistic regression to determine the association between
      ROSC and response time for fire apparatus first responders controlling for
      arrival of the EMS unit. SETTING: Out-of-hospital cardiac arrest cases in Houston
      between May 2008 and April 2013 when dual dispatch was used. PARTICIPANTS: A
      total of 6961 OHCA cases with the complete data needed for the analysis. MAIN
      OUTCOME MEASURES: Logistic regression of the dependence of OHCA survival using
      the indicator ROSC, as related to the fire first responder response times
      controlling for subsequent arrival of the EMS. RESULTS: Fire apparatus arrived
      first in 46.7% of cases, a median value of 1.5 minutes before an EMS unit.
      Controlling for subsequent arrival time of EMS has no effect on ROSC achieved by
      the fire first responder. If the firefighters had not responded, the resulting
      1.5-minute increase in response time equates to a decrease in probability of
      attaining ROSC of 20.1% for cases regardless of presenting heart rhythm and a
      47.7% decrease for ventricular fibrillation cases in which bystander
      cardiopulmonary resuscitation was initiated. CONCLUSIONS: The firefighter first
      responder not only improved response time but also greatly increased
      survivability independent of the arrival time of the better-equipped EMS unit,
      validating the public health benefit of the dual dispatch policy in Houston.

PMID- 30211770
TI  - (2R,6R)-Hydroxynorketamine promotes dendrite outgrowth in human inducible
      pluripotent stem cell-derived neurons through AMPA receptor with timing and
      exposure compatible with ketamine infusion pharmacokinetics in humans.
AB  - The mechanisms underlying the prolonged antidepressant effects after a single
      infusion of ketamine are only partially understood. Ketamine's half-life of ~2 h
      cannot explain antidepressant effects that last for 1 week, suggesting the
      triggering of long-lasting neuroplasticity. Recent human pharmacokinetics (PK)
      data indicate that a ketamine metabolite, (2R,6R)-hydroxynorketamine (HNK),
      persists in the high submicromolar range for additional 6-12 h. As in rodents HNK
      can induce dendrite outgrowth through AMPA receptor-mediated mechanisms, in this
      work, we aimed to show that HNK produces similar effects in human neurons at
      concentrations and exposure time compatible with human PK after ketamine
      infusion. Human dopaminergic neurons were differentiated in-vitro from inducible
      pluripotent stem cells obtained from healthy donors. Exposure to submicromolar
      HNK for 6 h produced dendrite outgrowth when measured 3 days after exposure. This
      neuroplasticity was similar to that obtained with exposure to low micromolar
      concentrations of ketamine for 1 or 6 h. HNK and ketamine effects were blocked by
      pretreatment with the AMPA receptor antagonists NBQX and GYKI 52466, and by the
      mammalian target of rapamycin pathway blocker rapamycin. It is reasonable to
      conclude that the mechanistic similarity between ketamine and HNK and their
      diachronic brain exposure owing to the different plasma PK observed after single
      therapeutic ketamine infusion should contribute to the final sustained
      antidepressant action.

PMID- 30211771
TI  - Point-of-Care Ultrasound Abnormalities in Late-Onset Severe Preeclampsia:
      Prevalence and Association With Serum Albumin and Brain Natriuretic Peptide.
AB  - BACKGROUND: Pilot studies applying point-of-care ultrasound (POCUS) in
      preeclampsia indicate the presence of pulmonary interstitial edema, cerebral
      edema, and cardiac dysfunction. Laboratory markers of oncotic pressure (albumin)
      and cardiac dysfunction (brain natriuretic peptide [BNP]) may be abnormal, but
      the clinical application remains unclear. We investigated the prevalence of
      pulmonary interstitial syndrome (PIS), cardiac dysfunction, and increased optic
      nerve sheath diameter (ONSD) in late-onset preeclampsia with severe features. The
      primary aim was to examine the association between PIS or ONSD and maternal serum
      albumin level. The secondary aims were to explore the association between cardiac
      dysfunction and PIS, ONSD, BNP, and serum albumin level and between POCUS-derived
      parameters and a suspicious or pathological cardiotocograph. METHODS: Ninety-five
      women were enrolled in this prospective observational cohort study. A POCUS
      examination of lungs, heart, and ONSD was performed. PIS was defined as a
      bilateral B-line pattern on lung ultrasound and diastolic dysfunction according
      to an algorithm of the American Society of Echocardiography. ONSD >5.8 mm was
      interpreted as compatible with raised intracranial pressure (>20 mm Hg). Serum
      BNP and albumin levels were also measured. RESULTS: PIS, diastolic dysfunction,
      systolic dysfunction, and raised left ventricular end-diastolic pressure (LVEDP)
      were present in 23 (24%), 31 (33%), 9 (10%), and 20 (25%) women, respectively.
      ONSD was increased in 27 (28%) women. Concerning the primary outcome, there was
      no association between albumin level and PIS (P = .4) or ONSD (P = .63). With
      respect to secondary outcomes, there was no association between albumin level and
      systolic dysfunction (P = .21) or raised LVEDP (P = .44). PIS was associated with
      diastolic dysfunction (P = .02) and raised LVEDP (P = .009; negative predictive
      value, 85%). BNP level was associated with systolic (P < .001) and diastolic
      dysfunction (P = .003) and LVEDP (P = .007). No association was found between
      POCUS abnormalities and a suspicious/pathological cardiotocograph (P = .07).
      CONCLUSIONS: PIS, diastolic dysfunction, and increased ONSD were common in
      preeclampsia with severe features. Cardiac ultrasound abnormalities may be more
      useful than albumin levels in predicting PIS. The absence of PIS may exclude
      raised LVEDP. The further clinical relevance of PIS and raised ONSD remains to be
      established. BNP level was associated with cardiac ultrasound abnormalities.
      Although this study was not designed to directly influence clinical management,
      the findings suggest that POCUS may serve as a useful adjunct to clinical
      examination for the obstetric anesthesiologist managing these complex patients.

PMID- 30211772
TI  - Provider Education and Vaporizer Labeling Lead to Reduced Anesthetic Agent
      Purchasing With Cost Savings and Reduced Greenhouse Gas Emissions.
AB  - Anesthetic agents are known greenhouse gases with hundreds to thousands of times
      the global warming impact compared with carbon dioxide. We sought to mitigate the
      negative environmental and financial impacts of our practice in the perioperative
      setting through multidisciplinary staff engagement and provider education on flow
      rate reduction and volatile agent choice. These efforts led to a 64% per case
      reduction in carbon dioxide equivalent emissions (163 kg in Fiscal Year 2012,
      compared with 58 kg in Fiscal Year 2015), as well as a cost savings estimate of
      $25,000 per month.

PMID- 30211774
TI  - In Response.

PMID- 30211773
TI  - The Perioperative Management of Ascending Aortic Dissection.
AB  - Acute aortic syndromes are a distinct group of pathologies involving the wall of
      the aorta that present acutely and can be potentially fatal unless treated in a
      timely fashion. The syndrome is dominated by aortic dissections, which comprise
      >=95% of all such presentations. Those involving the ascending aorta are
      particularly lethal and require specific and early surgical treatment compared to
      dissections involving other parts of the aorta. The surgical repair of an
      ascending aortic dissection presents multiple challenges to the anesthesiologist.
      Thoughtful management throughout the perioperative period is critical for
      minimizing the significant morbidity and mortality associated with this
      condition. In this narrative review, we provide an overview of the perioperative
      management of patients presenting for the surgical repair of an ascending aortic
      dissection. Preoperative discussion focuses on assessment, hemodynamic
      management, and risk stratification. The intraoperative section includes an
      overview of anesthetic management, transesophageal echocardiographic assessment,
      and coagulopathy, as well as surgical considerations that may influence
      anesthetic management.

PMID- 30211775
TI  - Trainability of Application of the Correct Cricoid Force: Time to Rely on
      Devices?

PMID- 30211776
TI  - Organizational Factors Associated With Technical Efficiency of Nursing Care in US
      Intensive Care Units.
AB  - BACKGROUND: Few studies have evaluated technical efficiency of nursing care, and
      no such studies have been conducted in intensive care units (ICUs). PURPOSE: To
      explore relative technical efficiency of US ICUs and identify organizational
      factors associated with efficiency in providing quality of nursing care. METHODS:
      A total of 404 adult ICUs from the 2014 National Database of Nursing Quality
      Indicators were included. Data envelopment analysis was used to estimate
      technical efficiency, and multilevel modeling was employed to determine effects
      of organizational factors on efficiency. RESULTS: Nurse-to-patient ratio showed
      the strongest positive correlation with technical efficiency. Units in non-Magnet
      and small-size hospitals had higher technical efficiency than those in Magnet and
      medium- or large-size hospitals. CONCLUSIONS: A higher nurse-to-patient ratio
      greatly improved technical efficiency of nursing care in ICUs and the effect
      differed between hospitals. Administrators and policy makers can translate the
      study findings into management strategies to provide efficient nursing care in
      ICUs.

PMID- 30211777
TI  - Cotransmission of Malaria and HIV to Infants of Mothers Coinfected With Malaria
      and HIV in the HAART Era in Benin City, Nigeria.
AB  - INTRODUCTION: Malaria and HIV are vertically transmitted to infants. In an era
      where specific interventions are available to reduce the burden of malaria in
      pregnancy and vertical transmission of HIV, we examined the transmission and
      cotransmission of HIV and malaria to infants of mothers coinfected with malaria
      and HIV. METHODS: A cross-sectional analytic study performed on 101 HIV/malaria
      coinfected mothers and their infants for whom DNA polymerase chain reaction
      results were available. Blood film for malaria parasites was performed on cord
      blood and peripheral blood on days 1, 3, and 7 in the newborns. Maternal
      peripheral blood film for malaria parasite was performed at delivery, and
      placental tissue was obtained for confirmation of placental malaria by histology.
      All infants received DNA polymerase chain reaction testing for HIV at 6-8 weeks
      of life. RESULTS: Cotransmission of malaria and HIV occurred in 2 (1.98%)
      infants. Vertical transmission of HIV occurred in 7 (7%) babies, whereas
      congenital malaria was present in 32 (31.7%) babies. The transmission of HIV and
      presence of congenital malaria were not significantly associated with each other
      P = 1.000. Of the 88 babies of mothers who commenced highly active antiretroviral
      treatment (HAART) before pregnancy, 5 (5.7^) had HIV, which was significantly
      less than 2 (40%) of 5 babies of mothers who commenced HAART during pregnancy P =
      0.04. CONCLUSIONS: Among mothers coinfected with malaria and HIV, vertical
      transmission of malaria and HIV was not associated with each other. HAART reduces
      vertical transmission of HIV especially if started before pregnancy.

PMID- 30211779
TI  - Brief Report: The Anti-HIV-1 ADCC-Mediating Antibodies From Cervicovaginal
      Secretions of HIV-Infected Women Have an Ability to Mediate Lysing of Autologous
      CD4+ HIV-Infected Cells.
AB  - BACKGROUND: Fragment crystallizable region of antibody-mediated mechanism such as
      antibody-dependent cellular cytotoxicity (ADCC) has been identified as an
      important component of immune protection against HIV. We assessed whether the
      anti-HIV antibodies mediating ADCC from cervicovaginal lavages (CVLs) of HIV
      infected women have an ability to mediate lysing of autologous CD4 HIV-infected
      cells. METHODOLOGY: The CVLs of 62 HIV-infected (37 long-term slow progressors
      and 25 with progressive HIV infection: progressors) and 20 HIV-uninfected Indian
      women with high risk of HIV acquisition were tested for the presence of ADCC
      mediating anti-HIV antibodies against HIV-1 C Env in a fluorometric assay.
      Furthermore, we tested the ability of these antibodies to mediate ADCC-dependent
      killing of the autologous HIV-infected CD4 T cells using paired peripheral blood
      mononuclear cells containing target and effector cells. RESULTS: The numbers of
      ADCC responders were significantly higher in long-term slow progressors (34/37)
      as compared to the progressor group (9/25) with no significant difference in the
      magnitude. The magnitude of response was inversely associated with detectable CVL
      viral load (P < 0.003). The lysis of target cells was significantly higher in
      enriched IgG fraction as compared to the respective non-IgG fraction. The ADCC
      antibodies from CVLs significantly reduced the frequency of HIV-1 Env-activated
      autologous CD4 T cells in the presence of autologous effector cells. CONCLUSIONS:
      The presence of ADCC antibodies in CVLs with an ability to mediate lysing of HIV
      infected autologous CD4 T cells provides evidence of their promising contribution
      to mucosal defense against HIV-1 and has implications in designing prophylactic
      and immunotherapeutic strategies.

PMID- 30211780
TI  - Associations of catechol-O-methyltransferase (rs4680) single nucleotide
      polymorphisms with opioid use and dose among adults with chronic pain.
AB  - Catechol-O-methyltransferase (COMT) regulates extracellular catecholamines. A
      widely studied COMT single nucleotide polymorphism (rs4680) changes the
      translated amino acid from valine to methionine (Val158Met); the polymorphism has
      been shown to influence opioid use. The aims of this study were to investigate
      the influence of COMT Val158Met on the likelihood and dose of opioid use in
      adults with chronic pain. Adults with chronic pain consecutively admitted to an
      outpatient pain rehabilitation program were recruited for study participation (N
      = 298). Individuals were genotyped for COMT Val158Met (rs4680). The polymorphism
      was analyzed using an additive and codominant genotype model. The distribution of
      genotypes was 23% (N = 70) for Val/Val, 49% (N = 146) for Val/Met, and 27% (N =
      82) for Met/Met (Hardy-Weinberg, P > 0.90). No significant association was
      observed between opioid use and genotype under the additive model; however, a
      significant association was observed under the codominant model (P = 0.027). A
      post hoc comparison demonstrated that the Met/Met genotype was more likely to use
      opioids compared with the Val/Met genotype (P = 0.0089). No significant
      association was observed between morphine equivalent dose and genotype under the
      additive model; however, a significant association was observed under the
      codominant model (P = 0.0496). A post hoc comparison demonstrated that the
      Val/Met (P = 0.019) and Met/Met (P = 0.043) genotypes used greater morphine
      equivalent dose compared with the Val/Val genotype. This study extends key
      knowledge about the influence of the Met/Met genotype and Met allele on opioid
      use in adults with chronic pain.

PMID- 30211781
TI  - Targeting the Nav1.8 ion channel engenders sex-specific responses in
      lysophosphatidic acid-induced joint neuropathy.
AB  - Joint neuropathic pain occurs in a subset of arthritis patients, and
      lysophosphatidic acid (LPA) has been implicated as a mediator of joint
      neuropathy. The mechanism by which LPA promotes neuropathic pain is unknown but
      may be related to altered signalling of the voltage-gated sodium channel Nav1.8
      located on nociceptors. Because arthritis and neuropathic pain are more prevalent
      in females, this study aimed to explore potential sex differences in the
      development of LPA-induced joint neuropathy and whether Nav1.8 played a role in
      the associated neuropathic pain. Joint neuropathy was induced in male and female
      Wistar rats (179-284 g) by intra-articular injection of 50-ug LPA. Pain behaviour
      was assessed over 21 days using von Frey hair algesiometry. On day 21,
      electrophysiological recordings of joint primary afferents were conducted to
      measure peripheral sensitisation. Saphenous nerve morphology and expression of
      the nerve-damage marker ATF3 and Nav1.8 in ipsilateral dorsal root ganglions were
      compared on the basis of sex. The analgesic properties of the selective Nav1.8
      antagonist A-803467 was determined in pain behaviour and electrophysiology
      experiments. Females developed more severe mechanical allodynia than males after
      LPA treatment. Lysophosphatidic acid caused more pronounced demyelination of the
      saphenous nerve in females, but no sex differences were observed in the
      expression of ATF3 or Nav1.8 in dorsal root ganglion neurones. Blockade of Nav1.8
      channels with A-803467 resulted in a decrease in joint mechanosensitivity and
      secondary allodynia with females exhibiting a greater response. These findings
      suggest that LPA has sex-specific effects on joint neuropathy and Nav1.8 gating,
      which should be considered when treating neuropathic arthritis patients.

PMID- 30211782
TI  - An educational intervention to enhance nurse practitioner role transition in the
      first year of practice.
AB  - BACKGROUND AND PURPOSE: Role transition is a natural process that occurs when the
      registered nurse pursues additional education to become a nurse practitioner
      (NP). Role transition generates feelings of anxiety and insecurity, leading to a
      longer and more tumultuous adjustment. This study investigated whether an
      evidence-based role transition webinar would support NP role transition during
      this critical period. METHODS: This study was a nonrandomized, pretest-posttest,
      and single-group study using a convenience sample to address the research
      question: "Does completion of a role transition webinar enhance the perception of
      new NPs of their ability to perform well in their role?" CONCLUSIONS: The
      educational webinar was shown to have a positive influence on some aspects of the
      participant's reported perceptions of NP role transition. Having practical and
      assessable educational interventions to optimize NP role transition and
      determining factors that contribute to the success of these interventions would
      be prudent. IMPLICATIONS FOR PRACTICE: This is the first quantitative study to
      investigate the positive association between an online educational intervention
      and NP role transition. A timelier and less tumultuous transition would allow NPs
      to perform more effectively in their new role.

PMID- 30211783
TI  - I Serve 2: Identifying and caring for military-connected children in civilian
      primary care settings.
AB  - Military children make tremendous sacrifices in support of a parent(s) military
      service. More than two million children have a parent who is serving or has
      served in the Armed Forces. Research shows that military-connected children are
      at higher risk of physical, psychological, and behavioral health issues. While
      "resilient" is the word used to describe most military children, it is important
      to recognize the stresses/stressors of military life- that military children
      serve too-to support and care for them.

PMID- 30211778
TI  - Early and Highly Suppressive Antiretroviral Therapy Are Main Factors Associated
      With Low Viral Reservoir in European Perinatally HIV-Infected Children.
AB  - BACKGROUND: Future strategies aiming to achieve HIV-1 remission are likely to
      target individuals with small reservoir size. SETTING: We retrospectively
      investigated factors associated with HIV-1 DNA levels in European, perinatally
      HIV-infected children starting antiretroviral therapy (ART) <6 months of age.
      METHODS: Total HIV-1 DNA was measured from 51 long-term suppressed children aged
      6.3 years (median) after initial viral suppression. Factors associated with log10
      total HIV-1 DNA were analyzed using linear regression. RESULTS: At ART
      initiation, children were aged median [IQR] 2.3 [1.2-4.1] months, CD4% 37 [24-45]
      %, CD8% 28 [18-36] %, log10 plasma viral load (VL) 5.4 [4.4-5.9] copies per
      milliliter. Time to viral suppression was 7.98 [4.6-19.3] months. After
      suppression, 13 (25%) children had suboptimal response [>=2 consecutive VL 50-400
      followed by VL <50] and/or experienced periods of virological failure [>=2
      consecutive VL >=400 followed by VL <50]. Median total HIV-1 DNA was 43 [6195]
      copies/10 PBMC. Younger age at therapy initiation was associated with lower total
      HIV-1 DNA (adjusted coefficient [AC] 0.12 per month older, P = 0.0091), with a
      month increase in age at ART start being associated with a 13% increase in HIV
      DNA. Similarly, a higher proportion of time spent virally suppressed (AC 0.10 per
      10% higher, P = 0.0022) and the absence of viral failure/suboptimal response (AC
      0.34 for those with fail/suboptimal response, P = 0.0483) were associated with
      lower total HIV-1 DNA. CONCLUSIONS: Early ART initiation and a higher proportion
      of time suppressed are linked with lower total HIV-1 DNA. Early ART start and
      improving adherence in perinatally HIV-1-infected children minimize the size of
      viral reservoir.

PMID- 30211784
TI  - Self-teaching to improve patient confidence in resuscitation skills: A quality
      improvement project.
AB  - BACKGROUND AND PURPOSE: Sudden cardiac death occurs predominantly at home where
      cardiopulmonary resuscitation (CPR) is often not provided. We tested the
      hypothesis that a self-teaching kit distributed to patients would effectively
      increase self-confidence in CPR. METHODS: Patients seen by an advanced registered
      nurse practitioner in a general cardiology clinic were offered a self-teaching
      kit to learn CPR. Four-point scale survey questions were assessed at distribution
      and via phone call at 30 days. CONCLUSIONS: Kits were distributed to 21 patients;
      of whom, 17 (81%) patients used the kit. Patients reported greater self
      confidence of performing CPR (2.6 before versus 3.2 after, p < .05) and greater
      comfort if someone needed CPR (2.4 before versus 3.1 after, p < .05).
      IMPLICATIONS FOR PRACTICE: Self-teaching CPR kits were used by the substantial
      majority of patients and were effective at increasing both self-confidence and
      willingness to perform CPR. Similar nurse-run programs could increase awareness
      and impact of CPR in communities.

PMID- 30211785
TI  - Resilience From a Stakeholder Perspective: The Role of Next of Kin in Cancer
      Care.
AB  - OBJECTIVE: The aim of this article was to provide new knowledge on how next of
      kin are co-creators of resilient performance, as seen from the viewpoint of the
      healthcare personnel and managers. The following research question guided the
      study: How are next of kin involved in shaping resilience within cancer care in
      hospitals? METHODS: The design of the study is a case study of cancer departments
      in two Norwegian hospitals. Data collection included a total of 32 qualitative
      semistructured interviews at two organizational levels (managers and staff). The
      data were analyzed by ways of a directed content analysis according to
      Hollnagel's Resilience in Health Care framework of resilience potentials
      (anticipate, monitor, respond, learn). RESULTS: Next of kin are involved in
      creating and maintaining resilience in cancer care by different kind of
      activities and in-depth insight into the patient's condition, which strengthen
      all resilience potentials of responding, anticipation, monitoring, and learning.
      We have identified nine areas in which next of kin are co-creators in shaping
      resilience. Next of kin are important stakeholders, both as safety experts and as
      safety resources, helping healthcare professionals provide quality and safety in
      the patient care process under difficult conditions. Next of kin's knowledge of
      the patient's history, their observation of the patient over time within the
      hospital, at home, and across care transitions are key elements of their
      contribution. CONCLUSIONS: Next of kin complement healthcare professionals in all
      four potentials for resilient performance. The study suggests that the Resilience
      in Health Care framework takes into account the role of next of kin, as a
      stakeholder potential, because this has not previously been sufficiently
      considered.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- 30211786
TI  - Variations in the Organisms Causing Deep Surgical Site Infections in Fracture
      Patients at a Level I Trauma Center (2006-2015).
AB  - OBJECTIVES: To quantify the current bacteriology of deep surgical site infections
      (SSIs) after fracture surgery at 1 institution and to compare those data with
      historical controls at the same institution, assessing variations in infecting
      organisms over the past decade. DESIGN: Retrospective review. SETTING: Level I
      trauma center. PATIENTS/PARTICIPANTS: Two hundred forty-three patients requiring
      surgical intervention for deep SSI between January 2011 and December 2015 were
      compared with 211 patients requiring surgical intervention for deep SSI between
      December 2006 and December 2010. INTERVENTION: None. MAIN OUTCOME MEASUREMENTS:
      Bacteria were categorized as Staphylococcus aureus, coagulase-negative
      staphylococci (CoNS), Streptococcus, Enterococcus, gram-negative rods (GNR), gram
      positive rods, anaerobes, or negative cultures. The proportion of each bacterial
      type was determined and compared with previously published data from the same
      trauma center (December 2006 to December 2010). RESULTS: Patients most commonly
      had S. aureus infections (48%), followed by GNR (40%) and CoNS (19%). The
      proportion of CoNS species (26% vs. 12%, P < 0.01) in infected patients was
      significantly higher during the current study period compared with historical
      controls. The proportion of S. aureus species in infected patients was
      significantly less during the current study period (39% vs. 56%, P < 0.01). The
      reduction in the proportion of S. aureus species in infected patients was driven
      by a decrease in the proportion of methicillin-resistant S. aureus (MRSA) in the
      overall sample. CONCLUSIONS: Bacteriology of deep SSI of fractures has changed
      substantially over the past decade at our center, specifically the proportions of
      GNR, CoNS, and MRSA. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions
      for Authors for a complete description of levels of evidence.

PMID- 30211787
TI  - A Comparision Of The Open, Semi-Extended Parapatellar Versus Standard Entry
      Tibial Nailing Techniques and Knee Pain: A Randomized Controlled Trial.
AB  - OBJECTIVE: To determine if an open, semi-extended, parapatellar tibial nailing
      technique (SEK) imparts any undue knee symptoms/pain compared to the traditional
      infrapatellar tibial nailing technique (FK). DESIGN: Randomize Controlled Trial
      SETTING:: Academic Level 1 Trauma Center PATIENTS:: Forty-seven patients with
      AO/OTA 42A-C tibial shaft fractures. INTERVENTION: Patients were randomized to
      treatment with either a SEK or FK technique. MAIN OUTCOME: A subset score (SS
      IKDC) in the International Knee Documentation Committee (IKDC) pertaining to knee
      symptoms/pain. RESULTS: Final follow-up was collected at one year for 24 SEK and
      23 FK patients. No significant differences were found between the groups in
      regards to demographics, injury or surgery related variables. The two techniques
      did have equivalent symptoms scores (mean for the difference [SEK-FK]: 0.29, 90%
      CI: -4.16, 4.75) but did not have equivalent pain scores (mean for the difference
      [SEK-FK]: 0.2, 90% CI: -3.18 - 3.59). When comparing demographic and injury
      related variables to the SS-IKDC, only Kellgren-Lawrence classification was
      statistically significant (p = 0.026), where increasing presence of
      osteoarthritis was associated with lower scores. CONCLUSION: The results of this
      single-center RCT show that SEK and FK techniques for tibial nailing are
      equivalent in regards to knee symptoms (defined as +/- 5 points on the SS-IKDC)
      but not specifically pain which showed trends towards decreasing knee pain with
      the open SEK technique. This RCT demonstrates that the use of the open semi
      extended, parapatellar technique for tibial nailing should not be associated with
      any higher likelihood of knee pain/symptoms than the traditional flexed knee,
      infrapatellar technique. LEVEL OF EVIDENCE: Therapeutic Level 1.

PMID- 30211788
TI  - Single-Screw Fixation Compared With Double Screw Fixation for Treatment of Medial
      Malleolar Fractures: A Prospective Randomized Trial.
AB  - OBJECTIVES: To determine whether single or double screw (DS) fixation of medial
      malleolar fractures results in better long-term health outcomes. DESIGN:
      Randomized clinical trial; sealed envelope technique. SETTING: Level 1 Trauma
      Hospital at University of Calgary, Canada. PATIENTS: One hundred forty patients
      were randomized to receive either 1 or 2 screws to reduce a medial malleolar
      fracture. Thirteen patients were excluded because of loss to follow-up (n = 127).
      INTERVENTION: Surgical fixation of the medial malleolar fracture was performed
      using 1 or 2 stainless steel screws. MAIN OUTCOME MEASUREMENTS: Primary outcome
      was comparison of physical functioning summary score on Short Form 36
      questionnaires between patients in the 2 groups. Secondary objectives were to
      compare the Ankle Hindfoot Scale and operating room time. Clinical and
      radiographic assessment occurred at the time of injury and 2, 6 weeks, 3, 6, 12,
      and 24 months postoperatively. RESULTS: Fourteen patients crossed over from the
      DS group to the single screw (SS) group based on intraoperative decisions by the
      surgeon (fragment too small for 2 screws), leaving the SS (n = 75) and DS groups
      (n = 52). There was no difference in the operating room time, SF36, or Ankle
      Hindfoot Scale at all follow-up time points. CONCLUSIONS: SS medial malleolar
      fixation provides an equally safe and effective method of fracture care as
      compared to DS fixation. Twenty percent of patients receiving 2 screws can be
      expected to crossover to receive SS fixation as a safer alternative. LEVEL OF
      EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete
      description of levels of evidence.

PMID- 30211789
TI  - Interfacility Transfer Is a Risk Factor for Venous Thromboembolism in Lower
      Extremity Fracture Patients.
AB  - OBJECTIVE: To compare the incidence of venous thromboembolism (VTE) among
      patients with pelvic and/or lower extremity fractures directly admitted to our
      institution versus those transferred from an outside hospital for definitive
      management. DESIGN: Retrospective cohort. SETTING: Tertiary care orthopaedic
      hospital. PATIENTS: Six hundred ninety patients who received definitive care for
      a lower extremity fracture at our institution between 2010 and 2017.
      INTERVENTION: Interfacility transfer for definitive management of pelvic or lower
      extremity fracture. MAIN OUTCOME MEASUREMENTS: VTE incidence and time to surgery.
      RESULTS: The interfacility transfer (TR) group comprised 126 patients, and the
      direct admission (DA) group comprised 564 patients. TR patients had a
      significantly higher incidence of VTE compared with the DA group: 9.5% versus
      0.7%, respectively (P < 0.001). Time to surgery was also longer in the TR group
      compared with the DA group: 3.05 +/- 3.00 days versus 2.16 +/- 2.42 days,
      respectively (P = 0.005). Demographics for TR and DA did not significantly differ
      with regard to age, sex, length of stay, or American Society of Anesthesiologist
      score. In the TR group, no complete and explicit documentation regarding
      thromboprophylaxis administration while at the outside facility was found.
      CONCLUSIONS: Patients undergoing interfacility transfer for definitive management
      of pelvic and lower extremity fractures are at a significantly increased risk of
      the development of VTE. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions
      for Authors for a complete description of levels of evidence.

PMID- 30211790
TI  - Does the Coexistence of Multiple Segmental Rib Fractures in Polytrauma Patients
      Presenting with "Major" Vertebral Fracture Affect Care and Acute Outcomes?
AB  - OBJECTIVE: To determine if operating on "major" vertebral fractures leads to
      premature abortion of surgery and/or other acute cardiopulmonary complications.
      DESIGN: Retrospective review CLINICAL SETTING:: Level 1 trauma center
      PATIENTS/PARTICIPANTS AND INTERVENTION:: We retrospectively queried our
      institutional Trauma Registry for all cases presenting with concomitant rib
      fractures and surgically managed vertebral fractures. MAIN OUTCOME MEASUREMENTS:
      The main outcomes included the surgical outcome (aborted vs successfully
      performed), total and ICU length of stay (LOS), adverse discharge, mortality and
      functional outcomes. RESULTS: We found 57 cases with concomitant segmental rib
      fractures and surgically managed vertebral fractures. Seven patients (12%)
      received a rib fixation of which 1 received prior to vertebral fixation and 6
      after. Importantly, 4 vertebral fixation cases (7.02%) had to be aborted intra
      operatively due to inability to tolerate prone positioning for surgery. For case
      control analysis, we performed propensity score matching to obtain matched
      controls, i.e. cases of vertebral fixation but no rib fractures. On matched case
      control analysis, patients with concomitant segmental rib fractures and vertebral
      fractures were found to have higher ICU LOS (Median=3 days(IQR=0-9) vs 8.4days,
      p=0.003), while total LOS, frequency of complete, incomplete or functional spinal
      cord injury, discharge to rehab and discharge to nursing home were found to
      similar between the two groups. CONCLUSION: Our findings demonstrate that
      segmental rib fractures with concomitant vertebral fractures undergoing surgical
      treatment represent a subset of patients that may be at increased risk for
      intraoperative cardio-pulmonary complications and rib fixation prior to prone
      spine surgery for cases in which the neurological status is stable is reasonable.

PMID- 30211792
TI  - Decreased Reoperations and Improved Outcomes With Reverse Total Shoulder
      Arthroplasty in Comparison to Hemiarthroplasty for Geriatric Proximal Humerus
      Fractures: A Systematic Review and Meta-Analysis.
AB  - OBJECTIVES: We sought to compare range of motion, clinical outcome scores, and
      complications after reverse total shoulder arthroplasty (RSA) and
      hemiarthroplasty (HA) in geriatric patients with acute proximal humerus
      fractures. DATA SOURCES: We searched MEDLINE (1946-2017), EMBASE (1947-2017), the
      Cochrane Central Register of Controlled Trials (1898-2017) and ClinicalTrials.gov
      in October 2017. No limits were used in the database search. We also manually
      reviewed reference lists of included studies. We did not restrict studies based
      on language. STUDY SELECTION: We included all randomized controlled trials and
      cohort studies in which the study population had a mean age of 65 or older,
      received RSA or HA to treat an acute proximal humerus fracture, and had a minimum
      follow-up of 6 months. DATA EXTRACTION: Two independent reviewers used a
      standardized data collection form to extract relevant information from included
      studies. Discrepancies were resolved by consensus or a third party if consensus
      could not be reached. Study authors were contacted for missing or incomplete
      data. DATA SYNTHESIS: Using a random effects model, we calculated mean
      differences (MD) and standardized mean differences (SMD) for continuous outcomes;
      we calculated relative risk (RR) for dichotomous outcomes. RESULTS: Fifteen
      studies were included in the meta-analysis, including 421 patients treated with
      RSA and 492 treated with HA for a total of 913 patients. Compared to HA, the RSA
      group had significantly improved pain scores (SMD = 0.74, p<0.001), outcome
      scores (SMD = 0.63, p<0.001), and forward flexion (MD = 24.3 degrees , p <0.001).
      Compared to RSA, the HA group had a significantly increased risk of re-operation
      (RR = 2.8, p= 0.02). There were no differences between the groups with regard to
      external rotation (p=0.31) or deep infection (p = 0.90). CONCLUSIONS: Aggregating
      available research suggests that RSA results in improved range of motion,
      clinical outcome scores, and rates of all-cause re-operation with no difference
      in infection rates. Utilizing RSA for the treatment of acute proximal humerus
      fractures in the elderly population may result in improved short- and medium-term
      outcomes compared to HA. Future work should evaluate long-term outcomes to see if
      the benefits of RSA persist.

PMID- 30211791
TI  - Surgical Fixation of Geriatric Sacral U-Type Insufficiency Fractures: A
      Retrospective Analysis.
AB  - OBJECTIVES: To define the incidence of sacral U-type insufficiency fracture and
      describe management of a consecutive series of patients with this injury. DESIGN:
      Retrospective analysis. SETTING: Single Level II trauma center.
      PATIENTS/PARTICIPANTS: Sixteen adult patients with sacral U-type insufficiency
      fractures treated over a 36-month period. INTERVENTION: Patients were indicated
      for percutaneous screw fixation of the posterior pelvis if they had posterior
      pelvic pain that prohibited mobilization. MAIN OUTCOME MEASUREMENTS: Visual
      analog scale for pain, distance ambulated on postoperative day 1, and change in
      sacral kyphosis. RESULTS: The sacral U-type insufficiency fracture incidence was
      16.7% (19/114); average patient age was 75 years. Delayed surgery was performed
      after primary nonoperative treatment had failed in 62.5% (10/16) at an average 83
      days postinjury. Acute surgery was performed in 37.5% (6/16) at an average 5 days
      postinjury. Distance ambulated on postoperative day 1 was 114.4 feet [95%
      confidence interval (CI) (50.6, 178.2)] and 88.7 feet [95% CI (2.8, 174.6)] in
      the delayed and acute surgery groups, respectively, P = 0.18. Change in visual
      analog scale for pain was -3.2 [95% CI (-5.0, -1.4)] and -3.7 [95% CI (-7.0, 
      0.4)] in the delayed and acute surgery groups, respectively, P = 0.15. Change in
      sacral kyphosis from presentation to surgery was 12.3 degrees [95% CI (6.7,
      17.9)] and 0.3 degrees [95% CI (-0.2, 0.9)] in the delayed and acute surgery
      groups, respectively, P < 0.01. Minimum follow-up was 12 months. CONCLUSIONS:
      Treatment of sacral U-type insufficiency fractures by percutaneous screw fixation
      permits early mobilization, provides rapid pain relief, and prevents progressive
      deformity. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors
      for a complete description of levels of evidence.

PMID- 30211793
TI  - Use of Inherent Anteversion of an Intramedullary Nail to Avoid Malrotation in
      Comminuted Femur Fractures: A Prospective Case- Control Study.
AB  - OBJECTIVES: To (1) evaluate using the inherent anteversion of a second or third
      generation femoral nail to set the version of the femur during locked
      intramedullary nailing of comminuted femoral shaft fractures (Espinosa Technique
      [ET]) and compare it with our traditional method (traditional group [TG]) and (2)
      assess the variation of anteversion because of the inherent play in the nail
      itself. DESIGN: A prospective IRB-approved study. SETTING: Academic US Level 1
      Trauma Center. PATIENTS: Fifty-two consecutive patients with comminuted femur
      fractures all completed the study. INTERVENTION: The first 27 patients had the
      anteversion determined using the patellar shadow and lesser trochanter (TG), and
      the next 25 patients were treated by ET. MAIN OUTCOME MEASURE: Computed
      tomography scanogram for femoral anteversion and length in the normal versus
      operated femur. RESULTS: A >15 degree difference from native to operated legs was
      found in 8/27 TG (29%, 95% CI 15.3%-54.2%), with a mean difference of 11.6 +/-
      10.2 degrees (95% CI 8.8-16.17) verses 1/25 in the ET group (2.5%, 95% CI 0%
      15.3%), with a mean difference of 4.8 +/- 6.2 degrees (95% CI 1.38-8.9) (P =
      0.0068). There was a 5 degree variability in our ability to center the proximal
      locking screw in the femoral head and 5 degrees variation in distal locking.
      CONCLUSIONS: The inherent anteversion of a second generation nail can be used to
      minimize malrotation of the femur after comminuted fractures during locked
      intramedullary nailing in patients with normal anteversion and is superior to our
      present fluoroscopic technique. LEVEL OF EVIDENCE: Therapeutic Level III. See
      Instructions for Authors for a complete description of levels of evidence.

PMID- 30211794
TI  - Operative setup to improve sagittal syndesmotic reduction - technical tip.
AB  - We analyzed the operative measures that may be used to reduce the likelihood of
      sagittal syndesmotic malreduction. Hence, we propose a simple technical tip to
      avoid sagittal plane malreduction of the fibula within the syndesmosis in ankle
      fractures. Supporting the leg under the heel should be avoided when performing
      syndesmotic reduction for unstable malleolar fractures and support under the calf
      should be used instead. Our observations have been confirmed in six cadaver
      specimens. We observed that there was a significant anterior subluxation of the
      fibula when the leg was supported under the heel. No significant difference
      between the intact and unstable state was present when the leg was supported
      under the calf.In conclusion, during syndesmotic reduction and fixation in supine
      position, supporting the foot under the heel should be avoided.

PMID- 30211795
TI  - Childhood Adversity and Pain Facilitation.
AB  - OBJECTIVE: This study investigated whether childhood adversity would be
      associated with hypersensitivity on two measures of central pain facilitation:
      area of secondary allodynia and temporal summation of second pain (TSSP), and
      whether pain facilitation would be explained by adult posttraumatic stress
      disorder (PTSD) symptoms. METHOD: Participants endorsing high (n = 31) and low (n
      = 31) childhood adversity underwent capsaicin-induced secondary allodynia and
      TSSP testing. The tests were conducted a week apart with test order
      counterbalanced. RESULTS: Larger areas of secondary allodynia were observed in
      the high adversity group compared with the low adversity group (F(1,60) = 4.81, p
      = .032). This group difference was largely (62%) explained by greater PTSD
      symptoms in the high adversity group. Although no overall difference was found in
      TSSP slopes (p = .886), this was attributed to an order by group interaction
      (F(1,58) = 5.07, p = .028) and low power. Subsequent analyses revealed positive
      TSSP slopes in the high adversity group when TSSP testing was performed first,
      and this order effect was associated with blunted sympathetic responses to TSSP
      on the first visit. The two facilitation measures were unrelated (p = .631).
      CONCLUSIONS: Larger areas of secondary allodynia were observed in the high
      adversity group, which was explained largely by PTSD symptoms. This suggests that
      adversity-related changes in pain facilitation may underlie the association
      between childhood adversity and generalized widespread pain. Although TSSP was
      affected by previous testing, adversity-related pain facilitation was observed
      when TSSP testing occurred first. Finally, adversity was not associated with a
      consistent pattern of hypersensitivity across the two measures of central pain
      facilitation.

PMID- 30211796
TI  - Superiority of Multidetector Computed Tomography With 3-Dimensional Volume
      Rendering Over Plain Radiography in the Assessment of Spinal Surgical
      Instrumentation Complications in Patients With Cancer.
AB  - OBJECTIVE: The objective of this study was to compare multidetector computed
      tomography (MDCT) images with volume-rendered translucent display (VRTLD) series
      to plain radiographs for evaluating spinal surgical instrumentation after
      resection and reconstruction for spinal malignancies. METHODS: In 44 patients
      with tumor resection and spinal reconstruction, 17 with complications, 3
      neuroradiologists evaluated plain radiographs, MDCT images alone, VRTLD images
      alone, and MDCT images with VRTLD images for identifying complications in 3
      categories: subsidence/migration, construct fracture, and screw loosening. Each
      category was scored as 1 (complications), 2 (no complications), or 3 (not sure),
      and the minimum score was used for analyses. Clinical/surgical outcomes were the
      reference standard. RESULTS: Sensitivity, specificity, and accuracy (95%
      confidence interval), respectively, were as follows: MDCT/VRTLD, 100%, 100%, 100%
      (91.96%-100.00%); MDCT alone, 88.24%, 100%, 95.45% (84.53%-99.44%); VRTLD alone,
      82.35%, 96.3%, 90.91% (78.33%-97.47%); plain radiographs, 52.94%, 100%, 81.82%
      (67.29%-91.81%). CONCLUSIONS: Multidetector computed tomography with VRTLD series
      seems best for evaluation of spinal instrumentation after tumor resection and
      reconstruction.

PMID- 30211797
TI  - Effect of Statistically Iterative Image Reconstruction on Vertebral Bone Strength
      Prediction Using Bone Mineral Density and Finite Element Modeling-A preliminary
      study.
AB  - Statistical iterative reconstruction (SIR) using multidetector computed
      tomography (MDCT) is a promising alternative to standard filtered back projection
      (FBP), because of lower noise generation while maintaining image quality. Hence,
      we investigated the feasibility of SIR in predicting MDCT-based bone mineral
      density (BMD) and vertebral bone strength from finite element (FE) analysis. The
      BMD and FE-predicted bone strength derived from MDCT images reconstructed using
      standard FBP (FFBP) and SIR with (FSIR) and without regularization (FSIRB0) were
      validated against experimental failure loads (Fexp). Statistical iterative
      reconstruction produced the best quality images with regard to noise, signal-to
      noise ratio, and contrast-to-noise ratio. Fexp significantly correlated with
      FFBP, FSIR, and FSIRB0. FFBP had a significant correlation with FSIRB0 and FSIR.
      The BMD derived from FBP, SIRB0, and SIR were significantly correlated. Effects
      of regularization should be further investigated with FE and BMD analysis to
      allow for an optimal iterative reconstruction algorithm to be implemented in an
      in vivo scenario.

PMID- 30211798
TI  - Current Update on Desmoid Fibromatosis.
AB  - OBJECTIVE: The purpose of this article is to review the etiopathogenesis,
      molecular cytogenetics, histopathology, clinical features, and multimodality
      imaging features of desmoid fibromatosis. Recent advances in the management of
      desmoid fibromatosis will also be discussed. CONCLUSIONS: Desmoid fibromatosis is
      a rare soft tissue neoplasm with a high incidence of local recurrence. Imaging
      plays an important role in the diagnosis and management of this disease.

PMID- 30211799
TI  - Comparison of Abdominal Computed Tomographic Enhancement and Organ Lesion
      Depiction Between Weight-Based Scanner Software Contrast Dosing and a Fixed-Dose
      Protocol in a Tertiary Care Oncologic Center.
AB  - OBJECTIVE: This study aimed to evaluate the quality of enhancement and solid
      organ lesion depiction using weight-based intravenous (IV) contrast dosing
      calculated by injector software versus fixed IV contrast dose in oncologic
      abdominal computed tomographic (CT) examinations. METHODS: This institutional
      review board-exempt retrospective cohort study included 134 patients who
      underwent single-phase abdominal CT before and after implementation of weight
      based IV contrast injector software. Patient weight, height, body mass index, and
      body surface area were determined. Two radiologists qualitatively assessed
      examinations (4 indicating markedly superior to -4 indicating markedly inferior),
      and Hounsfield unit measurements were performed. RESULTS: Enhancement (estimated
      mean, -0.05; 95% confidence interval [CI], -0.19 to 0.09; P = 0.46) and lesion
      depiction (estimated mean, -0.01; 95% CI, -0.10 to 0.07; P = 0.79) scores did not
      differ between CT examinations using weight-based IV contrast versus fixed IV
      contrast dosing when a minimum of 38.5 g of iodine was used. However, the scores
      using weight-based IV contrast dosing were lower when the injector software
      calculated and delivered less than 38.5 g of iodine (estimated mean, -0.81; 95%
      CI, -1.06 to -0.56; P < 0.0001). There were no significant differences in
      measured Hounsfield units between the CT examinations using weight-based IV
      contrast dosing versus fixed IV contrast dosing. CONCLUSIONS: Oncologic CT image
      quality was maintained or improved with weight-based IV contrast dosing using
      injector software when using a minimum amount of 38.5 g of iodine.

PMID- 30211800
TI  - Use of Postpartum Magnetic Resonance Imaging for Diagnosis and Classification of
      Retained Placenta Tissue.
AB  - OBJECTIVE: To study the potential application of magnetic resonance imaging (MRI)
      for classification of retained placental tissue (RPT) in the uterus postnatally.
      METHODS: Twenty-two patients with clinically or pathologically proven RPT were
      studied. RESULTS: The thickness ratio (D1/D2) of invaded (D1) to normal (D2)
      myometrium could be categorized into 3 groups (>0.6, 0.1-0.6, and <0.1)
      correlating with the 3 types of RPT: accreta vera (RPA), increta (RPI), and
      percreta (RPP) (r = -0.861, P < 0.01). After uterine arterial embolization, the
      RPT showed lower signal intensity than the myometrium without flow voids on T2
      weighted images. Two cases of RPP showed gradual enhancement, except 1 case of
      infection and 2 cases that did not involve enhancement examinations, whereas 17
      cases of RPA and RPI showed early enhancement. CONCLUSIONS: Magnetic resonance
      imaging can facilitate diagnosis of RPT severity. Dynamic contrast enhancement
      can indicate RPT activity and blood supply, thereby ensuring appropriate clinical
      decision making.

PMID- 30211801
TI  - CT Window Blending for Evaluation of Multicompartmental Thoracic Pathology.
AB  - Standard computed tomography windows are limited in the thorax because they can
      only display 1 tissue at a time. Computed tomography window blending allows for
      simultaneous viewing of all 3 tissues in a single image, which may improve
      evaluation of diseases that contiguously affect multiple compartments. In this
      article, we use examples to illustrate the utility of window blending in
      aggressive infections, metastatic cancer, and penetrating trauma.

PMID- 30211802
TI  - Changes in Proximal Femoral Shape During Fetal Development.
AB  - BACKGROUND: Walker and Goldsmith's classic article on fetal hip joint development
      reported that neck/shaft angle did not change from 12 weeks of gestational age
      through term while version increased from 0 to 40 degrees. This suggests no
      change in coronal alignment during development, a conclusion we dispute. By re
      examining their data, we found that the true neck/shaft angle (tNSA) decreased by
      7.5 degrees as version increased by 40 degrees from 12 weeks of gestational age
      to term. METHODS: Four investigators measured both femoral version and neck-shaft
      angle from photographs published by the authors of femurs at multiple stages of
      maturation from 12 weeks of gestational age to term. The tNSAs and inclination
      angles were calculated for each femur illustrated using previously validated
      formula. Changes in the morphology of the femur over time were analyzed using a
      Student t test. Interobserver and intraobserver reliability were also determined
      by the Pearson R coefficient. RESULTS: As reported by Walker and Goldsmith,
      apparent neck/shaft angle (aNSA) did not significantly change during maturation,
      whereas version increased by 40 degrees. However, tNSA decreased by 7.5 degrees
      during maturation, while the inclination increased by 32 degrees over the same
      period. This paper demonstrates angular changes in both the coronal and
      transverse planes with a 4:1 ratio of angular change in the transverse and
      coronal planes respectively. Interobserver Pearson coefficient R=0.98 and an
      intraobserver Pearson coefficient R=0.99. CONCLUSIONS: Although Walker and
      Goldsmith reported angular changes only in the transverse plane, we conclude that
      they identified angular changes in both the coronal and transverse planes. Here
      we show it is mathematically necessary for tNSA to decrease, if aNSA remains
      constant as version increases. CLINICAL RELEVANCE: A reader who is not well
      versed in the difference between aNSA and tNSA or version and inclination cannot
      appreciate what Walker and Goldsmith presented. Surgeons operating on the
      proximal femur also benefit from understanding these distinctions.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- 30211803
TI  - Loss of Midline Function in Brachial Plexus Birth Palsy Patients.
AB  - BACKGROUND: Loss of midline function impairs the child's ability to perform
      certain activities of daily living such as dressing, buttoning, and perineal
      care. The purpose of this study was to assess brachial plexus birth palsy (BPBP)
      patients with loss of midline function with respect to etiology and treatment.
      METHODS: A retrospective review of all BPBP patients with loss of midline
      function was performed. The modified Mallet scale was used with internal rotation
      assessed via hand on spine and hand to belly. Demographics, extent of BPBP, prior
      surgical intervention, procedure(s) performed to correct the loss of midline
      function, complications, and outcomes were assessed. RESULTS: In total, 20
      patients were identified with loss of midline function as defined by the
      inability to reach midline and touch their umbilicus. Nineteen patients had
      previously undergone tendon transfers about the shoulder with or without
      arthroscopic capsular release to improve external rotation. After the initial
      surgery, modified Mallet scores improved 1 grade for abduction, hand to mouth,
      hand to neck, and external rotation without altering the hand to spine category.
      However, the internal rotation category (hand to umbilicus) decreased from an
      average 2.71 preoperatively to an average 2.15 postoperatively. Nine patients
      underwent a derotational humeral osteotomy to improve midline function. The
      average correction of internal rotation was 47.8 degrees (range, 20 to 85
      degrees). After this surgery, modified Mallet scores remained unchanged for hand
      to spine; however, the scores improved back to 2.7 for the internal rotation
      category. Two complications were noted including 1 plate fracture and 1 fracture
      through a screw hole. CONCLUSIONS: BPBP patients who undergo surgical procedures
      to improve shoulder external rotation and/or obtain joint reduction may
      inadvertently lose midline function. Derotational humeral osteotomy can
      effectively restore midline function, which is needed to perform activities of
      daily living. Surgical procedures to improve external rotation should be
      performed in a manner that minimizes limitation of midline functions. LEVEL OF
      EVIDENCE: Level III-therapeutic.

PMID- 30211804
TI  - Progression of Structural Brain Changes in Patients With Chronic Pancreatitis and
      Its Association to Chronic Pain: A 7-Year Longitudinal Follow-up Study.
AB  - OBJECTIVES: Temporal information about the structural brain changes in chronic
      pancreatitis (CP) and its relation to the clinical manifestations is lacking.
      This study investigated changes in morphological brain parameters over 7 years in
      painful CP patients, compared with controls. METHODS: In this 7-year longitudinal
      magnetic resonance imaging study, we included 23 CP patients and 14 controls.
      Gray matter volume (GMV) and cortical thickness were examined using voxel-based
      and surface-based morphometry. In addition, patients completed pain
      questionnaires and diary. RESULTS: At baseline, patients had reduced GMV and
      cortical thickness in widespread brain areas compared with controls. After 7
      years of follow-up, the GMV loss was more pronounced in patients compared with
      controls, particularly in precentral gyrus and putamen. Moreover, an increase in
      pain scores was associated with a less reduction of thalamic GMV (P = 0.046),
      whereas an increase in brief pain inventory score was associated with more
      reduction in cortical thickness of precentral (P = 0.005) and superior temporal
      gyri (P = 0.019), indicating that brain morphological alterations are associated
      with the pain. CONCLUSIONS: Chronic pancreatitis pain is associated with
      morphological brain changes over time in several areas, reflecting that brain
      plasticity may be a consequence of repeated long-term nociceptive signaling.

PMID- 30211805
TI  - Grading by the Ki-67 Labeling Index of Endoscopic Ultrasound-Guided Fine Needle
      Aspiration Biopsy Specimens of Pancreatic Neuroendocrine Tumors Can Be
      Underestimated.
AB  - OBJECTIVES: There is an increasing need for grading with small endoscopic
      ultrasound-guided fine needle aspiration biopsy (EUS-FNAB) specimens for the
      proper diagnosis and therapy selection of patients with unresectable pancreatic
      neuroendocrine tumors (PanNET). However, our understanding of EUS-FNAB specimen
      grading is limited compared with surgically resected specimens. METHODS: We
      retrospectively determined Ki-67 labeling index (LI) of 33 matched EUS-FNAB and
      surgically resected PanNETs with digital image analyzer. Pairwise grades between
      the matched biopsy and surgically resected PanNET specimens were compared.
      RESULTS: The mean Ki-67 LI was higher in surgically resected PanNET specimens
      (5.5%) than in biopsy specimens (3.2%; P = 0.022). There was moderate agreement
      between the Ki-67 LI grades when individually evaluated matched biopsy and
      resected specimen pairs were compared (kappa value = 0.62; P < 0.0001). However,
      discordance was noted in 6 cases (18%), and all of them were either grade 2 or 3
      in resected PanNETs. CONCLUSIONS: Although Ki-67 LI grading of EUS-FNAB specimens
      may be concordant with that of matched surgically resected specimens in a large
      proportion of the PanNET cases, Ki-67 LI grading of EUS-FNAB specimens should be
      carefully applied in clinical practice because of the possibility of grading
      underestimation with grade 2 to 3 PanNET cases.

PMID- 30211806
TI  - Free Thyroxine Determination in the Emergency Department Is a Predictor of Acute
      Pancreatitis Evolution.
AB  - OBJECTIVE: The aim of this study was to determine the prevalence and type of
      thyroid hormone levels alterations in patients with acute pancreatitis (AP) and
      analyze if variations are useful AP progression predictors. METHODS: Three groups
      of patients were analyzed: AP patients (n = 90), abdominal pain patients (n =
      30), and healthy control subjects (n = 40). Usual blood parameters for AP
      diagnosis and prognosis, thyroid-stimulating hormone (or thyrotropin), FT4 (free
      thyroxine), FT3 (free triiodothyronine), and TT3 (total triiodothyronine) levels
      were analyzed. RESULTS: Thyroid hormone level alterations were detected only
      within the AP group (41% of total cases), being the reduction in T3 levels the
      most frequently detected deviation (15.6% of FT3 and 8.3% of TT3 cases).
      Alterations were not influenced by age or sex. Free thyroxine average values were
      also significantly higher in the AP group, compared with the healthy control
      group (P = 0.0005), resulting as independent predictors of both severity and
      mortality. Mortality in this group was 50%, with deceased patients showing FT4
      levels above the reference limit. CONCLUSIONS: Our results show that FT4 level
      determination during the initial clinical evaluation of patients admitted to the
      emergency service with AP can be included as a severity indicator to help
      determine the differential care of these cases.

PMID- 30211808
TI  - Disparities in Self-reported Access to Patient-centered Medical Home Care for
      Children With Special Health Care Needs.
AB  - BACKGROUND: Efforts to transform primary care have been underway for over a
      decade. Yet, we lack understanding of the progress made in scaling up this care
      model nationwide and on whether patient-centered medical home (PCMH) has
      benefited every group of children with special health care needs (CSHCNs).
      OBJECTIVE: The main objective of this study was to examine variation in caregiver
      service experience concordant with PCMH care over time and by child
      characteristics. RESEARCH DESIGN: This was a cross-sectional pooled data analysis
      using the 2003-2012 Medical Expenditures Panel Survey data for CSHCNs, aged 5-17
      years. Logistic regressions were implemented, accounting for child and parent
      sociodemographic, child's health insurance, and contextual characteristics. PCMH
      concordant care and each component were constructed as binary variables and child
      functional impairment was measured with the Columbia Impairment Scale. RESULTS:
      Thirty-one percent of children reported medical home concordant care;
      comprehensive (83%) and compassionate (82%) care were most prevalent, and the
      least common were accessible care (59%) and patient-centered care (60%). PCMH
      concordant care significantly increased nationwide between 2003 and 2012, but
      disparities remained based on child needs and sociodemographic characteristics.
      Multivariate regressions showed variation across medical home components.
      CONCLUSIONS: Despite increased parent perception of care that is concordant with
      medical home care over time, disparities remain among high-need CSHCNs. Future
      research may focus on better understanding how clinical settings tailor this care
      model, particularly on providing increased access and patient-centered care, to
      better serve children at the highest need.

PMID- 30211807
TI  - Analysis of a Step-Up Approach Versus Primary Open Surgical Necrosectomy in the
      Management of Necrotizing Pancreatitis: Experience in a Cohort of Patients at a
      US Academic Medical Center.
AB  - OBJECTIVES: An increasing number of providers have begun to use a minimally
      invasive step-up approach as opposed to traditional surgical necrosectomy in the
      management of acute necrotizing pancreatitis. Studies have shown mixed results,
      thus we hypothesized that the step-up approach is safer and associated with
      decreased mortality and length of stay (LOS). METHODS: This is a retrospective
      cohort study of patients admitted from January 2010 to March 2015 who underwent
      interventions for walled-off pancreatic necrosis (WOPN). Primary outcomes
      included LOS after intervention and mortality, in-hospital and 90-day, with
      secondary outcomes of procedural complications. RESULTS: Sixty-nine patients
      developed WOPN requiring intervention during the study period. In-hospital
      mortality was 5.6% (n = 2) in the step-up cohort compared with 18.2% (n = 6) in
      the surgical cohort (relative risk, 3.27; 95% confidence interval, 0.71-15.09).
      Ninety-day mortality was 9.1% (n = 3) in the step-up cohort and 21.9% (n = 7) in
      the surgical cohort (relative risk, 2.41; 95% confidence interval, 0.68-8.50).
      Postintervention LOS was 8 days in the step-up cohort and 17 days in the surgical
      cohort (P = 0.62). CONCLUSIONS: A step-up approach, as compared with primary
      surgical necrosectomy in the management of WOPN, results in clinically
      significant decreases in mortality and LOS.

PMID- 30211809
TI  - Utilization and Adherence in Medical Homes: An Assessment of Rural-Urban
      Differences for People With Severe Mental Illness.
AB  - BACKGROUND: The complex nature of managing care for people with severe mental
      illness (SMI), including major depression, bipolar disorder, and schizophrenia,
      is a challenge for primary care practices, especially in rural areas. The team
      based emphasis of medical homes may act as an important facilitator to help
      reduce observed rural-urban differences in care. OBJECTIVE: The objective of this
      study was to examine whether enrollment in medical homes improved care in rural
      versus urban settings for people with SMI. RESEARCH DESIGN: Secondary data
      analysis of North Carolina Medicaid claims from 2004-2007, using propensity score
      weights and generalized estimating equations to assess differences between urban,
      nonmetropolitan urban and rural areas. SUBJECTS: Medicaid-enrolled adults with
      diagnoses of major depressive disorder, bipolar disorder or schizophrenia.
      Medicare/Medicaid dual eligibles were excluded. MEASURES: We examined utilization
      measures of primary care use, specialty mental health use, inpatient
      hospitalizations, and emergency department use and medication adherence. RESULTS:
      Rural medical home enrollees generally had higher primary care use and medication
      adherence than rural nonmedical home enrollees. Rural medical home enrollees had
      fewer primary care visits than urban medical home enrollees, but both groups were
      similar on the other outcome measures. These findings varied somewhat by SMI
      diagnosis. CONCLUSIONS: Findings indicate that enrollment in medical homes among
      rural Medicaid beneficiaries holds the promise of reducing rural-urban
      differences in care. Both urban and rural medical homes may benefit from targeted
      resources to help close the remaining gaps and to improve the success of the
      medical home model in addressing the health care needs of people with SMI.

PMID- 30211811
TI  - Use of gene expression profile testing as a prognostic tool in early-stage
      cutaneous melanoma - compelling but not ready for primetime.
AB  - Advances in the field of molecular genetics have led to the development of
      multiple tests capable of identifying genetic changes within cutaneous melanoma.
      Although the majority of these tests are currently used for diagnostic purposes,
      their potential use as prognostic tools is rapidly emerging. A new 31-gene
      expression profile test has been developed that promises to accurately predict
      metastatic risk in patients with early-stage cutaneous melanoma. Although current
      data are promising, many questions remain in terms of its potential effects in
      patient care. Thus, before this test is used routinely in clinical practice, we
      recommend that it first be performed as part of current adjuvant treatment trials
      as a potential predictive marker or other high-quality studies investigating
      relevant outcomes resulting from changes in the clinical management of patients
      on the basis of the gene expression profile test results.

PMID- 30211812
TI  - Successful treatment with intralesional talimogene laherparepvec in two patients
      with immune checkpoint inhibitors refractory advanced melanoma.
AB  - Monoclonal antibodies that block the programmed death-1 (anti-PD-1) or cytotoxic
      T-lymphocyte antigen-4 (CTLA-4) immune checkpoint receptors (pembrolizumab,
      nivolumab, ipilimumab, or the combination of nivolumab with ipilimumab) are
      approved treatment option for patients with advanced melanoma. Over half of all
      patients are refractory to these immunotherapies and are in need of alternative
      or complementary treatment options. Talimogene laherparepvec (T-VEC) is a first
      in-class intralesionally delivered oncolytic immunotherapy, which has proven
      efficacy in the treatment of advanced melanoma. A proportion of patients treated
      with T-VEC will benefit from an abscopal response of noninjected metastases
      indicative of a systemic antitumor immune response elicited by the intratumoral
      injections. At present it remains unknown whether the systemic antitumor
      responses elicited by T-VEC are nonredundant with immune-checkpoint blockade.
      Recent data on potential synergy between T-VEC and both PD-1 and CTLA-4 blockade
      suggest that the mechanism of action may be complementary. We report on the
      successful treatment with intralesional T-VEC of two female patients with
      locoregionally advanced BRAF V600 wild-type melanoma who previously progressed on
      anti-PD-1 and anti-CTLA-4 inhibitors.

PMID- 30211814
TI  - Differences in Obesity Among Black and White Children, Adolescents, and Adults
      With Congenital Heart Disease.
AB  - BACKGROUND: Congenital heart disease (CHD) survivors have an elevated risk for
      obesity-related comorbidities, but little is known about racial differences in
      obesity rates for this population. OBJECTIVE: The authors aimed to compare rates
      of obesity in CHD survivors to national estimates using National Health and
      Nutrition Examination Assessment Survey (NHANES) and to characterize racial
      disparities in obesity among CHD survivors across age ranges. METHODS:
      Retrospective chart review included 4496 CHD survivors (4050 white and 446 black)
      with a range of lesion severities from a pediatric and an adult medical center.
      RESULTS: White children with CHD had a higher prevalence of obesity compared with
      NHANES estimates. In contrast, white young adults with CHD had a lower prevalence
      of obesity compared with NHANES. Blacks with CHD had a 58% increased risk of
      obesity in young adulthood and a 33% increased risk in late adulthood compared
      with whites with CHD. CONCLUSIONS: Obesity interventions are needed among CHD
      survivors across the lifespan, particularly among adult non-Hispanic blacks.

PMID- 30211813
TI  - Results from phase II trial of HSP90 inhibitor, STA-9090 (ganetespib), in
      metastatic uveal melanoma.
AB  - Uveal melanoma (UM) is a rare form of melanoma without effective therapy. The
      biology of UM relies on several heat-shock protein 90 (Hsp90)-dependent molecules
      such as MET, MEK and AKT, making Hsp90 inhibition a rational approach. Patients
      with stage IV UM, measurable disease, and no previous chemotherapy were eligible.
      Patients received either ganetespib 200 mg weekly (cohort A) or 150 mg twice a
      week (cohort B). Primary endpoint response rate (RR) was assessed by RECIST. A
      total of 17 patients were accrued for this study, with seven in cohort A and 10
      in cohort B. Liver metastases were present in 59%. Response outcomes included one
      partial response, four stable disease, 11 progressive disease, and one withdrawal
      for ORR: 5.9% and disease control rate of 29.4%. Progression-free survival was
      1.6 months (cohort A) and 1.8 months (cohort B). Overall survival was 8.5 months
      (cohort A) and 4.9 months (cohort B). An overall 31% of adverse events were grade
      3-4 and were mostly related to gastrointestinal toxicities. Early on-treatment (1
      months) positron emission tomography showed reduction in metabolic activity in
      24% of patients, suggesting a pharmacodynamic effect of Hsp90 inhibition. These
      early metabolic changes did not seem to be durable and/or clinically significant
      in relation to the 2-month response assessment. Hsp90 inhibition with ganetespib
      resulted in modest clinical benefit on two dosing schedules and was associated
      with significant, although manageable, gastrointestinal toxicity. Evidence of
      pharmacodynamic activity for Hsp90 inhibition was observed via positron emission
      tomography, which did not translate into clinical benefit, suggesting rapid
      development of resistance.

PMID- 30211815
TI  - Dietary Vitamin C Deficiency Is Associated With Health-Related Quality of Life
      and Cardiac Event-free Survival in Adults With Heart Failure.
AB  - BACKGROUND: Vitamin C deficiency is prevalent in adults with heart failure (HF).
      Little is known about the relationship of dietary vitamin C deficiency with
      health outcomes in adults with HF. OBJECTIVE: The study's aim was to determine
      the relationships of vitamin C deficiency measured at baseline with health
      related quality of life (HRQOL) and cardiac event-free survival in patients with
      HF measured 1 year later. METHOD: A total of 251 patients with HF completed a 4
      day food diary. Dietary vitamin C deficiency was defined as daily intake less
      than the estimated average requirement from the Institute of Medicine of 75 mg/d
      for men and 60 mg/d for women. Health-related quality of life was assessed using
      the Minnesota Living with Heart Failure Questionnaire at 12 months. Patients were
      followed for a median of 1 year to determine time to the first event of cardiac
      related hospitalization or death. Data were analyzed by hierarchical linear and
      Cox proportional hazards regressions. RESULTS: One hundred patients (40%) had
      vitamin C deficiency. Dietary vitamin C deficiency was associated with poorer
      HRQOL at 12 months (beta = 0.16, P = .02) after controlling for demographic and
      clinical variables. During the follow-up period, 59 patients (24%) had cardiac
      events. In Cox regression, vitamin C deficiency predicted shorter cardiac event
      free survival after adjusting for the same covariates (hazards ratio, 1.95; 95%
      confidence interval, 1.08-3.51). CONCLUSION: Vitamin C deficiency was associated
      with poorer HRQOL and shorter cardiac event-free survival in patients with HF.
      The findings suggest that encouraging patients with HF to consume a diet rich in
      fruits/vegetables to prevent vitamin C deficiency may lead to better health
      outcomes.

PMID- 30211816
TI  - Public Reporting of Cardiac Outcomes for Patients With Acute Myocardial
      Infarction: A Systematic Review of the Evidence.
AB  - BACKGROUND: Percutaneous coronary intervention (PCI) is recognized by both the
      American Heart Association and the American College of Cardiology as an optimal
      therapy to treat patients experiencing acute myocardial infarction (AMI) with ST
      segment elevation myocardial infarction. A health policy aimed at improving
      outcomes for the patient with AMI is public reporting of whether a patient
      received a PCI. OBJECTIVE: A systematic review was conducted to evaluate the
      effect of public reporting for patients with AMI, specifically for those patients
      who receive PCI. METHODS: EMBASE, MEDLINE, Academic Search Premier, Google
      Scholar, and PubMed were searched from inception through August 2017. Articles
      were selected for inclusion if researchers evaluated public reporting and
      included an outcome for whether a patient received a PCI during hospitalization
      for an AMI. Methodological quality of the included studies was evaluated, and
      findings were synthesized. RESULTS: Eight studies of high methodological quality
      were included in the review. Most studies found that, in areas of public
      reporting, patients were less likely to undergo a PCI and high-risk patients did
      not undergo a PCI. Researchers also found that patients with AMI had lower in
      hospital mortality after the implementation of public reporting, but only if
      these patients received a PCI. CONCLUSIONS: Although public reporting may have
      had intentions of improving care, there is strong evidence that this policy did
      not result in more timely PCIs or improved mortality of patients with AMI. In
      fact, public reporting resulted in unintended consequences of not providing care
      for the most vulnerable patients in fear of an adverse outcome.

PMID- 30211818
TI  - A nurse practitioner by any other name.

PMID- 30211817
TI  - Translation and Cross-cultural Adaptation of the Chinese Version of the Self-care
      of Hypertension Inventory in the Older Adults.
AB  - BACKGROUND: Hypertension is highly prevalent among the older adults. Self-care is
      an effective method for the secondary prevention of hypertension, but until now,
      there has been no specialized instrument to evaluate the ability for self-care in
      elderly Chinese patients with hypertension. OBJECTIVES: The aims of this study
      were to cross-culturally translate the Self-care of Hypertension Inventory into
      Chinese and apply it to elderly patients with preliminary hypertension. METHODS:
      This is a methodological study with steps that included translation, synthesis,
      back-translation, back-translation review, expert committee review, pretesting,
      and submission to authors. We conducted preliminary psychometric analyses that
      included content validity, item-total correlation, internal consistency
      reliability, principal factor analysis, and test/retest reliability. RESULTS: The
      translation equivalence was obtained between the adapted version and the original
      scale. The item-level content validity index had a range of 0.833 to 1. The scale
      level content validity average method and Cronbach alpha were 0.986 and 0.858 for
      the total scale, respectively. The test/retest reliability was 0.949. Principal
      factor analyses showed the presence of 4, 1, and 1 latent factors in 3 separate
      subscales. CONCLUSIONS: The Self-care of Hypertension Inventory has been
      successfully translated and cross-culturally adapted to Chinese. It is suitable
      for application to elderly Chinese patients with hypertension.

PMID- 30211819
TI  - Fostering leadership through the changing practice of the emergency nurse
      practitioner specialty.

PMID- 30211820
TI  - When should genomic testing be considered for cystic fibrosis?

PMID- 30211821
TI  - Nurse practitioners' time on nonbillable activities.

PMID- 30211822
TI  - Supporting lower-income working women to initiate breastfeeding: Learning who is
      breastfeeding and what helps.
AB  - BACKGROUND AND PURPOSE: Based on the Women, Work, and Wee Ones longitudinal
      study, mothers' likelihood of breastfeeding is examined across demographic and
      health variables. METHODS: Frequencies of breastfeeding and cosleeping by 285
      mothers from the Women, Work, and Wee Ones cohort are reported as related to
      mothers' work schedule, marital status, or mother or infant health. CONCLUSIONS:
      Breastfeeding rates were about 30% across most maternal characteristics. The
      frequency of mothers' breastfeeding was higher when mothers were both
      breastfeeding and cosleeping (breastfeeding-cosleeping), in comparison with
      breastfeeding only, as evident for mothers with nonstandard work schedules.
      Cosleeping was common across all mothers. Breastfeeding rates were low, perhaps
      reflecting challenges of early care. Premature infants were more likely to be
      cosleeping than breastfeeding. Approximately 30% of mothers breastfed across the
      different factors examined. IMPLICATIONS FOR PRACTICE: The information may help
      nurse practitioners in addressing early care needs and supporting breastfeeding
      across groups. Younger mothers were least likely to breastfeed and reported
      higher frequency of cosleeping. Overall breastfeeding frequency was higher when
      mothers were cosleeping. Nurse practitioners may find it important to provide
      clear information about safe infant sleep and safe approaches to protecting
      infants.

PMID- 30211823
TI  - Efficacy and safety of dupilumab for the treatment of moderate-to-severe atopic
      dermatitis in adults: A pooled analysis of two phase 2 clinical trials.
AB  - BACKGROUND AND PURPOSE: There is a need for new treatment options for moderate-to
      severe atopic dermatitis (AD) in adults. Dupilumab, a fully human anti
      interleukin-4 receptor alpha monoclonal antibody, has recently been approved for
      this indication. METHODS: A pooled analysis of a phase 2a (NCT01548404) and a
      phase 2b (NCT01859988) study and a subanalysis of the 2b study evaluated the
      efficacy and safety of subcutaneous dupilumab 300 mg once weekly (qw) and every 2
      weeks (q2w) in adults with moderate-to-severe AD. RESULTS: Dupilumab
      significantly improved clinical outcomes in both analyses at week 12. Itch was
      significantly improved in the pooled analysis as measured by peak pruritus
      Numerical Rating Scale, 5-dimension pruritus scale, and SCORing Atopic Dermatitis
      (SCORAD) Visual Analog Scale (VAS) pruritus scores (all p < .0001 vs. placebo at
      week 12). Sleep loss was significantly improved (SCORAD VAS sleep loss score; p <
      .0001 vs. placebo at week 12); similar results were shown for the q2w dose.
      Dupilumab had an acceptable safety profile. CONCLUSIONS: Consistent with previous
      studies, dupilumab qw and q2w significantly improved signs and symptoms of AD at
      week 12, including improvements in itch and sleep loss. IMPLICATIONS FOR
      PRACTICE: Subcutaneous dupilumab is an effective new treatment option for adults
      with moderate-to-severe AD.

PMID- 30211824
TI  - Liraglutide, a Glucagon-Like Peptide-1 Receptor Agonist, Attenuates Development
      of Cardiac Allograft Vasculopathy in a Murine Heart Transplant Model.
AB  - BACKGROUND: Advances in immunosuppressive therapy have significantly improved
      short-term but not long-term survival of cardiac transplant recipients; this is
      largely due to severe cardiac allograft vasculopathy (CAV). Glucagon-like peptide
      1 receptor (GLP-1R)-based therapy exerts physiological effects on the
      cardiovascular system in addition to its traditional role in controlling glucose.
      We have investigated the effects of liraglutide, a GLP-1R agonist, on the
      development of CAV in a murine heart transplant model. METHODS: Heterotopic
      murine cardiac transplantation was performed with a major histocompatibility
      complex class II (MHC-II)-mismatched model. Recipient mice were subcutaneously
      administered vehicle (0.9% saline solution) or liraglutide (300 MUgkg12 h) from
      the day of transplantation. Allografts were harvested at 2 or 8 weeks and
      histologically analyzed. Inflammatory infiltrates were measured by
      immunohistochemistry, and immunofluorescence and western blotting analyzes were
      used to evaluate GLP-1R expression and markers of endothelial-to-mesenchymal
      transition (EndMT) in cardiac allografts and human coronary artery endothelial
      cells (HCAECs) challenged with transforming growth factor-beta 1 (TGF-beta1).
      RESULTS: GLP-1R was predominantly localized to vascular endothelial cells and was
      up-regulated in cardiac allografts after liraglutide treatment. Liraglutide
      ameliorated CAV and cardiac fibrosis with reduced inflammatory cell infiltration
      and down-regulated expression of adhesion molecules. Liraglutide inhibited EndMT
      in allografts and attenuated EndMT by inhibiting Smad3 activation in TGF-beta1
      treated HCAECs. CONCLUSIONS: Administration of liraglutide from the time of
      transplantation up-regulated GLP-1R in the transplanted heart and reduced cardiac
      fibrosis, inflammation, and CAV development. Therefore, liraglutide may be a
      novel therapy for CAV.

PMID- 30211825
TI  - The Use of Donation After Cardiac Death Organs for Simultaneous Liver-Kidney
      Transplant: To DCD or Not to DCD?
AB  - BACKGROUND: Due to challenges with organ scarcity, many centers performing
      simultaneous liver-kidney transplant are opting to accept donation after cardiac
      death (DCD) organs as a means of facilitating earlier transplant and reducing
      death rates on the waitlist. It has been suggested however, that DCD organs may
      have inferior graft and patient survival posttransplant compared with donation
      after neurologic death (DND) organs. METHODS: We created a Markov model to
      compare the overall outcomes of accepting a DCD SLKT now versus waiting for a DND
      SLKT in patients waitlisted for SLKT, stratified by base MELD score (<= 20, 21
      30, >30). RESULTS: Waiting for DND SLKT was the preferred treatment strategy for
      patients with a MELD score of <= 30 (incremental value of 0.54 and 0.36 QALYs for
      MELD <= 20 and MELD 21-30 with DND versus DCD SLKT, respectively). The option to
      accept a DCD SLKT became the preferred choice for those with a MELD score > 30
      (incremental value of 0.31 QALYs for DCD versus DND SLKT). This finding was
      confirmed in a probabilistic sensitivity analysis and persisted when analyzing
      total life years obtained for accept DCD versus do not accept DCD. CONCLUSIONS:
      There is a benefit to accepting DCD SLKT for patients with MELD > 30. Although
      not accepting DCD SLKT and waiting for DND SLKT is the preferred option for
      patients with MELD <= 30, the incremental value is small.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- 30211826
TI  - Blood Pressure in De novo Heart Transplant Recipients Treated with Everolimus
      Compared with a Cyclosporine-Based Regimen: Results from the Randomized SCHEDULE
      Trial.
AB  - BACKGROUND: Systemic hypertension is prevalent in heart transplant recipients,
      and has been partially attributed to treatment with calcineurin inhibitors
      (CNIs). The SCHEDULE trial was the first randomized trial to study early
      withdrawal of CNIs in de novo heart transplant recipients, comparing an
      everolimus-based immunosuppressive regimen with conventional CNI-based treatment.
      As a prespecified secondary endpoint, blood pressure was repeatedly compared
      across treatment arms. METHODS: SCHEDULE was a prospective, multicenter,
      randomized, controlled, parallel-group, open-label trial in de novo adult heart
      transplant recipients, undertaken at transplant centers in Scandinavia. Blood
      pressure was assessed with 24-hour ambulatory blood pressure monitoring up to 3
      years after HTx in 83 patients. RESULTS: Overall, systolic blood pressure fell
      with time, from 138 +/- 15 mmHg 2 weeks after HTx to 134 +/- 11 mmHg after 12
      months and 132 +/- 14 mmHg after 36 months (p = 0.003). Diastolic blood pressure
      did not change over time. After 12 months, there was a numerically larger fall in
      systolic blood pressure in the everolimus arm (between-group difference 8 mmHg; p
      = 0.053), and after 36 months, there was a significant between group difference
      of 13 mmHg (p = 0.02) in favor of everolimus. CONCLUSIONS: In this first,
      randomized trial with early CNI avoidance in de novo HTx recipients, we observed
      a modest fall in systolic blood pressure over the first 1 - 3 years after
      transplantation. The fall in systolic blood pressure was more pronounced in
      patients allocated to everolimus.

PMID- 30211827
TI  - IL-17A Is Critical for CD8+ T Effector Response in Airway Epithelial Injury After
      Transplantation.
AB  - BACKGROUND: Airway epithelium is the primary target of trachea and lung
      transplant rejection, the degree of epithelial injury is closely correlated with
      obliterative bronchiolitis development. In this study, we investigated the
      cellular and molecular mechanisms of IL-17A-mediated airway epithelial injury
      after transplantation. METHODS: Murine orthotopic allogeneic trachea or lung
      transplants were implemented in wild type or RORgammat mice. Recipients received
      anti-IL-17A or anti-IFNgamma for cytokine neutralization, anti-CD8 for CD8 T-cell
      depletion, or STAT3 inhibitor to suppress type 17 CD4+/CD8+ T cell development.
      Airway injury and graft inflammatory cell infiltration were examined by
      histopathology and immunohistochemistry. Gene expression of IL-17A, IFNgamma,
      perforin, granzyme B, and chemokines in grafts was quantitated by real-time RT
      PCR. RESULTS: IL-17A and IFNgamma were rapidly expressed and associated with
      epithelial injury and CD8 T-cell accumulation after allotransplantation.
      Depletion of CD8 T cells prevented airway epithelial injury. Neutralization of IL
      17A or devoid of IL-17A production by RORgammat deficiency improved airway
      epithelial integrity of the trachea allografts. Anti-IL-17A reduced the
      expression of CXCL9, CXCL10, CXCL11, and CCL20, and abolished CD8 T-cell
      accumulation in the trachea allografts. Inhibition of STAT3 activation
      significantly reduced IL-17A expression in both trachea and lung allografts;
      however, it increased IFNgamma expression and cytotoxic activities, which
      resulted in the failure of airway protection. CONCLUSIONS: Our data reveal the
      critical role of IL-17A in mediating CD8 T effector response that causes airway
      epithelial injury and lung allograft rejection, and indicate that inhibition of
      STAT3 signals could drive CD8 T cells from Tc17 toward Tc1 development.

PMID- 30211828
TI  - NKG2C natural killer cells in bronchoalveolar lavage are associated with
      cytomegalovirus viremia and poor outcomes in lung allograft recipients.
AB  - BACKGROUND: Cytomegalovirus (CMV) infection is a risk factor for chronic lung
      allograft dysfunction (CLAD), which limits survival in lung allograft recipients.
      Natural killer (NK) cells that express the NKG2C receptor mediate CMV-specific
      immune responses. We hypothesized that NKG2C NK cells responding to CMV in the
      lung allograft would reduce CMV-related inflammation and would improve CLAD-free
      survival. METHODS: We prospectively followed 130 subjects who underwent lung
      transplantation from 2012 to 2016. Bronchoalveolar lavage (BAL) NK cells were
      immunophenotyped for NKG2C, maturation, and proliferation markers. CMV viral
      load, serologies, serial spirometry, and mortality were recorded from medical
      records. NK cell subset association with CMV endpoints were made using
      generalized estimating equation-adjusted linear models. BAL NKG2C NK cell
      association with CLAD-free survival was assessed by Cox proportional hazards
      modeling. RESULTS: NKG2C NK cells were more mature and proliferative than NKG2C-
      NK cells and represented a median of 7.8% of BAL NK cells. The NKG2C NK cell
      proportion increased prior to the first detection of viremia and was nearly
      tripled in subjects with high level viremia (>1000 copies/ml) compared with no
      detected viremia. Subjects with increased BAL NKG2C NK cells, relative to the
      median, had a significantly increased risk for CLAD or death (HR 4.2, 95% CI 1.2 
      13.3). CONCLUSIONS: The BAL NKG2C NK cell proportion may be a relevant biomarker
      for assessing risk of CMV viremia and quantifying potential CMV-related graft
      injury that can lead to CLAD or death.

PMID- 30211829
TI  - Patient Navigators in Transplantation - where do we go from here?

PMID- 30211830
TI  - Kidney Transplant in the Era of Modern Therapy for Multiple Myeloma.
AB  - Chronic kidney disease is common in patients with multiple myeloma. Historically,
      individuals with end-stage renal disease and multiple myeloma did poorly with
      renal transplantation due to higher mortality rates from the malignancy itself or
      associated comorbidities. However, over the past 2 decades, there have been
      significant advances in the treatment of multiple myeloma with the advent of new
      therapeutic agents resulting in an improvement of long-term survival. As a
      result, more individuals with multiple myeloma are being referred for kidney
      transplantation, especially those with good functional capacity and minimal
      comorbidities. Recent literature has suggested that certain patients with
      multiple myeloma can successfully undergo renal transplantation after stem
      transplantation with consideration for maintenance therapy, although caution
      should be used with immunomodulating drugs due to the anecdotally reported risk
      of acute rejection. Therefore, having a multidisciplinary approach with the
      transplant team and hematology both before and after transplant is crucial in
      maximizing the chance of success for these individuals. This review summarizes
      the literature on renal transplantation in patients with multiple myeloma as well
      as the therapeutic advancements that have occurred which may allow certain
      patients to undergo successful transplantation.

PMID- 30211832
TI  - Interhospital Transport of Pediatric Patients in Denmark: A Survey of Current
      Practice.
AB  - OBJECTIVES: No national guidelines exist in Denmark regarding interhospital
      transport of critically ill children. The aim of this study was to disclose which
      physicians actually accompany critically ill children during interhospital
      transports nationwide and whether the physicians have adequate clinical skills to
      perform interhospital transfers. METHODS: A questionnaire was sent to the
      youngest pediatrician on-call at every hospital in Denmark receiving pediatric
      emergencies except the tertiary Copenhagen University Hospital, Rigshospitalet.
      RESULTS: Seventeen pediatric departments were contacted (response rate, 100%).
      All departments indicated that they perform interhospital transport of pediatric
      patients. When presented with 5 cases, great heterogeneity in the choice of
      transport physician and accompanying staff was seen. With increasing severity,
      fewer pediatricians were willing to transport the children (24% vs 6%).
      Irrespective of the degree of severity, more transports were delegated to
      anesthesiologists than performed by pediatricians. Pediatricians who agreed to
      transport the infant and neonate had adequate competencies. In cases with older
      children, 0 to 75% of physicians who would do the transport had adequate clinical
      skills and experience in emergency pediatric respiratory and cardiovascular
      management. Training in interhospital transport was offered by 1 department; 6
      departments (35%) had local guidelines describing the management of pediatric
      transports. CONCLUSIONS: Great heterogeneity was found in the local transport
      strategies and practical skill sets of accompanying physicians. Overall, there is
      room for improvement in the management of interhospital transport of critically
      ill children in Denmark, perhaps by increasing the availability of specialized
      pediatric transport services for critically ill children nationwide.

PMID- 30211831
TI  - Open Randomized Multicenter Study to Evaluate Safety and Efficacy of Low
      Molecular Weight Sulfated Dextran in Islet Transplantation.
AB  - BACKGROUND: When transplanted human pancreatic islets are exposed to blood during
      intraportal infusion, an innate immune response is triggered. This instant blood
      mediated inflammatory reaction (IBMIR) activates the coagulation and complement
      cascades and leads to the destruction of 25% of all transplanted islets within
      minutes, contributing to the need, in most patients, for islets from more than 1
      donor. Low molecular dextran sulfate (LMW-DS) has been shown in experimental
      settings to inhibit IBMIR. METHODS: The CIT-01 study was a phase II, multicenter,
      open label, active control, randomized study. Twenty-four subjects were
      randomized to peritransplant intraportal and systemic treatment with either LMW
      DS or heparin, targeting an APTT of 150+/-10 and 50+/-5 seconds respectively. C
      peptide response was measured with a mixed meal tolerance test at 75 and 365 days
      after transplant. RESULTS: LMW-DS was safe and well tolerated with similar
      observed adverse events (mostly attributed to immunosuppression) as in the
      heparin arm. There was no difference in the primary endpoint (stimulated C
      peptide 75+/-5 days after the first transplant) between the 2 arms (1.33+/-1.10
      versus 1.56+/-1.36 ng/mL, p=0.66). Insulin requirement, metabolic parameters,
      Clarke and HYPO score, quality of life and safety were similar between the 2
      treatments groups. CONCLUSIONS: Even with low dosing, LMW-DS showed similar
      efficacy in preventing IBMIR to promote islet engraftment when compared to "state
      of-the art" treatment with heparin. Furthermore, no substantial differences in
      the efficacy and safety endpoints were detected, providing important information
      for future studies with more optimal dosing of LMW-DS for the prevention of IBMIR
      in islet transplantation.This is an open access article distributed under the
      Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use,
      distribution, and reproduction in any medium, provided the original work is
      properly cited.

PMID- 30211833
TI  - Unexpected Diagnosis in an Adolescent With Bruises and Ecchymosis: Celiac
      Disease.
AB  - Acquired coagulopathy is a rare but challenging diagnosis for pediatric emergency
      physicians. Although the coagulopathy usually presents with mild skin and mucosal
      hemorrhages, it also can lead to life-threatening events. Thus, accurate
      interpretation of hints obtained from a detailed history, physical examination,
      and laboratory findings is essential for the prompt diagnosis and management.
      This case demonstrates an uncommon cause of coagulopathy; celiac disease that
      presented with spontaneous bruises and ecchymosis in an adolescent.

PMID- 30211834
TI  - Repeat Laboratory Testing in the Pediatric Emergency Department: How Often and
      How Important?
AB  - BACKGROUND: Little is known about repeat testing for patients admitted to
      children's hospitals from the emergency department (ED). OBJECTIVE: The objective
      of this study was to describe the trend of repeat laboratory testing from a
      children's hospital ED. METHODS: Laboratory studies were analyzed for July 2002
      to June 2010 for complete blood counts (CBCs; 7 years), basic metabolic panels
      (BMPs; 2.5 years), and coagulation studies (7 years) ordered and reordered in the
      ED within 8 hours for patients admitted to the hospital. Results for tests were
      generated and classified into high, low, and normal based on reference ranges. To
      reflect actual practice, we expanded the normal range from 95% of lower bound to
      105% of upper bound. RESULTS: A total of 37,035 CBCs, 11,414 BMPs, and 3903
      coagulation studies were ordered. Proportions of these tests repeated were 0.9%,
      1.9%, and 1.9%, respectively. Mean time to repeat was 2 hours. For CBCs, 25% of
      repeats were for a missing component; 35% were for low platelet counts. Sixty
      eight percent of initial BMPs were repeated for high potassium. Half of
      coagulation studies were repeated for high prothrombin time; 36% were repeated
      for a missing component. On repeat, 75% of BMPs with high potassium levels and
      65% of CBCs with low platelet count returned normal values, but 16% of
      coagulation studies repeated for high prothrombin time returned normal values.
      CONCLUSIONS: Repeat ED laboratory testing occurs infrequently at a children's
      hospital, and a large proportion of repeats is attributed to missing results.
      When repeated, abnormal results on initial studies are often returned as normal.

PMID- 30211835
TI  - Pediatric Malpractice Claims in the Emergency Department and Urgent Care Settings
      From 2001 to 2015.
AB  - OBJECTIVES: This study aimed to provide an assessment of medical malpractice
      claims involving pediatric patients cared for in emergency department and urgent
      care settings. METHODS: We performed a retrospective review of all closed
      malpractice claims involving children (0-17 years old) originating from emergency
      department or urgent care centers from the Physician Insurers Association of
      America's Data Sharing Project database for a 15-year period (2001-2015).
      Reported data collected include medical specialty involved, medical diagnoses,
      chief medical factors, severity of resulting injury, claim disposition, average
      indemnity, and average defense costs. RESULTS: A total of 728 closed claims in
      pediatric emergency care settings were reviewed. Money was paid to the claimant
      in 30% of cases (220/728), with a total of US $70.3 million (average $319,513)
      paid to patients or families during the 15-year period. The most common resulting
      medical conditions were cardiac or cardiorespiratory arrest, appendicitis, and
      disorder of male genital organs. Error in diagnosis was the most common chief
      medical factor (41%), whereas those that involved failure or delay in admission
      to the hospital, which was the eighth most common chief medical factor, resulted
      in the highest average indemnity. Of the 728 closed claims, 220 involved a
      patient death (30%), but claims involving major permanent injury more often
      resulted in a payment. Of the 57 cases that went to trial, verdicts favored the
      physician in 47 cases (82%). CONCLUSIONS: Cardiac conditions, appendicitis, and
      disorder of the male genital organs are the most common medical conditions, and
      error in diagnosis is the most common chief medical factor in pediatric emergency
      care malpractice suits. It is important for providers practicing in these
      settings to be familiar with the common diagnoses and chief medical factors
      involved in these claims.

PMID- 30211836
TI  - Lazarus Syndrome - Challenges Created by Pediatric Autoresuscitation.
AB  - Pediatric autoresuscitation is extremely rare, with only 4 documented cases in
      the literature. The longest recorded time between stopping cardio pulmonary
      resuscitation (CPR) and return of spontaneous circulation is 2 minutes. We report
      a previously well 18-month-old who attended the emergency department after an
      unexplained cardiac arrest. After 10 cycles of CPR, resuscitation was stopped; 6
      minutes later, the patient had a return of spontaneous circulation and was
      transferred to the pediatric intensive care unit. The patient remains alive but
      with significant neurological impairment. There are a variety of theories
      regarding the pathology of pediatric autoresuscitation. The most commonly
      accepted model is that there is a degree of autopositive end-expiratory pressure
      impending venous return as a consequence of vigorous ventilation during CPR. This
      case challenges clinicians to reassess our current definition of death and
      reaffirms the need for clearer guidelines surrounding the certification of death.

PMID- 30211837
TI  - Characteristics of Children Cared for by a Physician-Staffed Helicopter Emergency
      Medical Service.
AB  - OBJECTIVES: The effectiveness of Japanese helicopter emergency medical services
      (HEMS) and interventions at the scene is not clear as regard children. For
      effective use of HEMS at the clinical scene, we need to clarify the
      characteristics of pediatric patients cared for by HEMS. Therefore, the objective
      of this study was to describe the characteristics of pediatric scene flights and
      to describe the procedures performed on the patients. METHODS: This was a
      retrospective cohort study based on the database for children aged younger than
      18 years who were cared for by physician-staffed HEMS of Ibaraki prefecture, in
      Japan. We reviewed the database for air medical transports conducted at our
      institution from July 2010 to December 2016. RESULTS: During the 6.5-year period,
      the Ibaraki HEMS attended to 288 children. The median age of the children was 11
      (interquartile range, 5-14) years. Of the total, 196 (68.1%) of the children had
      trauma-related injuries. The head was the most common site of significant
      injuries (12.4%). The most common cause of nontrauma incidents was seizure
      (9.0%). In 65.9% of the patients, the injury or illness was of mild or moderate
      severity at the scene. An intervention was applied at the scene in 76.0% of the
      cases: 75.1%, intravenous route; 6.9%, intubation; and 13.4%, drug
      administration. Of those patients, 29.1% were discharged from the emergency
      department. In-hospital mortality accounted for 1.5% (n = 2) of the cases.
      CONCLUSIONS: Although the condition at the scene of most of the pediatric
      patients transported by the physician-staffed HEMS was not severe, an
      intervention was frequently applied from the scene. Improving the dispatch
      criteria and monitoring compliance are needed for appropriate use of HEMS.

PMID- 30211838
TI  - Dental Abscess in Pediatric Patients: A Marker of Neglect.
AB  - OBJECTIVES: Neglect is defined as the persistent failure to meet a child or young
      person's basic physical or psychological needs. Dental caries is explicitly
      mentioned in guidance on child maltreatment. We discuss the link between dental
      caries and child abuse in patients presenting to the emergency department.
      METHODS: A review of patient medical records was undertaken within the Paediatric
      Emergency Department at Sunderland Royal Hospital, with the aim to determine
      whether neglect was considered as a possible contributory factor when a child or
      young person presented at triage with an "oral cavity" problem. RESULTS: Of the
      applicable cases with inferences of possible safeguarding concerns, 13% had these
      concerns documented. CONCLUSIONS: Child abuse recognition has become a prominent
      issue in recent years due to high profile cases. It is clear from this work,
      which resonates with the reported literature, that there is a lack of recognition
      of dental neglect being a possible indicator of more systemic abuse.There is
      likely underreporting of these cases to the relevant authorities.

PMID- 30211839
TI  - Left-Sided Appendicitis: More Than Meets the Eye.
AB  - Classic appendicitis is a common condition easily diagnosed by emergency care
      providers. However, atypical cases represent a diagnostic challenge and can
      contribute to increased morbidity from a delay in definitive care. It is
      important to recognize that atypical presentations have an increased risk for
      underlying anatomic variants, which may require additional imaging as part of
      management. We present a case of a 13-year-old previously healthy adolescent boy
      with acute onset of left-sided abdominal pain who was found to have appendicitis
      in the setting of underlying malrotation.

PMID- 30211840
TI  - Pediatric Conditions Requiring Interfacility Transport From Emergency
      Departments: A Statewide Study of Regionalization.
AB  - OBJECTIVES: Pediatric care is increasingly regionalized, increasing rates of
      interfacility transport (IFT). However, it is unknown what conditions most
      frequently require IFT. This study's objective was to identify high-frequency
      pediatric conditions requiring IFT. METHODS: This is a statewide retrospective
      observational study from 2010 to 2012 of pediatric patients (<18 years of age)
      who underwent IFT in Maryland. Patients were identified from the Health Care
      Utilization Project's database using probabilistic linkage. This study identified
      the 20 most common pediatric IFT conditions, and the conditions with the highest
      IFT rates. RESULTS: Probabilistic linkage was successful for 2254 records. The
      largest age category was 0 to 4 years (43%). The top 3 IFT conditions were asthma
      (13.5%), epilepsy (8.5%), and diabetes mellitus (6.6%). Diabetes mellitus had the
      highest IFT rate (24%), followed by appendicitis (15.5%) and internal obstruction
      (14.4%). CONCLUSIONS: Specific pediatric conditions commonly require IFT and had
      high IFT rates in this statewide study. In addition, the largest age group
      undergoing IFT was young children (0 to 4 years of age). This study provides
      specific detail regarding conditions and ages impacted by IFT, and emergency
      medical services should consider incorporating these findings into transport
      destination algorithms. In addition, public health stakeholders should address
      implications of the concentration of care for these common pediatric conditions
      and younger age groups.

PMID- 30211841
TI  - Early Life Factors and Eosinophilic Esophagitis: Building the Evidence.

PMID- 30211843
TI  - Classification and Nutrition Management of Acute Pancreatitis in the Pediatric
      Intensive Care Unit.
AB  - The aims of this retrospective cohort study were to classify the severity of
      patients admitted to the pediatric intensive care unit (PICU) with acute
      pancreatitis (AP) and to identify how many patients received appropriate
      nutritional management in accordance with more recent guidelines and the outcomes
      of those patients. Of the 54 children with AP, 12 (22.2%) had a primary diagnosis
      of AP (50% severe, 17% moderate) whereas 42 (77.8%) had a secondary diagnosis of
      AP (81% severe, 11.9% moderate). Just under half of the patients (48.1%) had
      enteral nutrition commenced before the third day of admission (50% with primary
      AP, 47.6% with secondary AP). The average time to initiation of enteral feeds was
      2.3 days for those that received enteral nutrition. 51.8% of patients received
      parenteral nutrition (25% with primary AP, 59.5% with secondary AP). Most
      patients received enteral nutrition late and parenteral nutrition was overused in
      patients with AP admitted to the PICU.

PMID- 30211842
TI  - IL-9 Alters Epithelial Barrier and E-cadherin in Eosinophilic Esophagitis.
AB  - BACKGROUND: Eosinophilic esophagitis (EoE) is a chronic Th2-assocated
      inflammatory condition accompanied by substantial impairments in epithelial
      barrier function and increased numbers of IL-9 expressing inflammatory cells.
      While IL-9 is known to affect barrier function in the intestine, the functional
      effects of IL-9 on the esophagus are unclear. Herein we aimed to understand the
      expression of the IL-9 receptor and effects of IL-9 on the epithelium in EoE.
      METHODS: We used esophageal biopsies from pediatric EoE patients with active and
      inactive disease to analyze the expression of the IL-9 receptor, the adherens
      junction protein E-cadherin and the tight junction protein claudin-1. We treated
      primary human esophageal epithelial cells with IL-9 to understand its effects on
      E-cadherin expression and function. RESULTS: Active EoE subjects had increased
      epithelial expression of IL-9 receptor mRNA and protein (p < 0.05) and decreased
      membrane bound E-cadherin (p < 0.01) and claudin-1 (p < 0.05) expression. IL-9
      receptor expression and mislocalized claudin-1 positively correlated and while
      membrane bound E-cadherin expression negatively correlated with the degree of
      histologic epithelial remodeling (p < 0.05). IL-9 decreased epithelial resistance
      in stratified primary human esophageal epithelial cells (p < 0.01) and membrane
      bound E-cadherin in epithelial cell monolayers (p < 0.01). CONCLUSION: These data
      suggest that IL-9, its receptor, and its effects on E-cadherin may be important
      mechanisms for epithelial barrier disruption in EoE.

PMID- 30211844
TI  - There Is No Excuse for Mortality Due to Lack of Competency and Training of
      Paediatric Endoscopists in Gastrointestinal Bleeding Therapy in 2018.
AB  - Acute upper gastrointestinal bleeding in children is possibly the last medical
      emergency which continues to lead to the death of a child due to the lack of
      competency/clinical judgement of the doctor, as opposed to the disease itself,
      leading to mortality despite optimum medical intervention. This is unacceptable
      in any circumstances in 2018. It occurs due to a number of conspiring factors
      including lack of appreciation of the clinical presentation requiring urgent
      endoscopic intervention; misapprehension of the urgency of timing required of
      such an intervention predicated on the severity of the gastrointestinal (GI)
      bleed; lack of application of a paediatric-specific validated score predicting
      for such endoscopic intervention; lack of skill in endo-haemostatic intervention
      techniques by paediatric endoscopists; poor training in such techniques among
      paediatric endoscopists; paucity of cases with lack of exposure of the paediatric
      endoscopist regularly to enable skills to be maintained, once acquired;
      reluctance of adult endoscopists in many centres to support paediatric GI
      bleeding services. In essence then the paediatric GI community urgently needs to
      identify centres of excellence to whom these children should be transferred.
      Transfer is safe in all but the most critical cases once stabilised with
      transfusion, octreotide/terlipressin and iv proton pump inhibitors. The resources
      are country-dependent but this is really no excuse. We must not let this parlous
      state of affairs continue. Solutions are explored in this article and please let
      this serve as a call to action for all those involved in this continuing debacle
      in order to save "save-able" lives.

PMID- 30211846
TI  - Development and Pilot Implementation of a Nutrition Curriculum and Rotation in
      Pediatric Gastroenterology Fellowships.
AB  - Structured nutrition rotations are rarely offered in pediatric gastroenterology
      fellowships. The NASPGHAN Nutrition Committee developed a curriculum to serve as
      the basis for a rotation in clinical nutrition. We worked directly with five
      fellowship programs to tailor the experience to individual institutions. As part
      of our pilot study, fellows completed knowledge assessments and self-assessment
      of comfort level at the start and end of the experience. We saw a trend in
      improvement of comfort level and increase in mean score on knowledge assessments,
      but the differences did not meet statistical significance. Fellows who completed
      the rotation had an increase in comfort level in all topics with most dramatic
      increase in nutrition management of cystic fibrosis, refeeding syndrome, and
      cholestasis.Objective measures of nutrition knowledge attainment and use of
      programmatic feedback to continually improve the learners' experience will help
      expand the nutrition curriculum to a broader audience.

PMID- 30211845
TI  - Causes of Treatment Failure In Children With Inflammatory Bowel Disease Treated
      With Infliximab: A Pharmacokinetic Study.
AB  - OBJECTIVES: Anti-tumor necrosis factor antibodies have led to a revolution in the
      treatment of inflammatory bowel diseases (IBD), however a sizable proportion of
      patients do not respond to therapy. There is increasing evidence suggesting that
      treatment failure may be classified as mechanistic, pharmacokinetic, or immune
      mediated. Data regarding the contribution of these factors in children with IBD
      treated with infliximab (IFX) are still incomplete. The aim was to assess the
      causes of treatment failure in a prospective cohort of pediatric patients treated
      with IFX. METHODS: This observational study considered 49 pediatric (median age
      14.4) IBD patients (34 Crohn's disease, 15 ulcerative colitis) treated with IFX.
      Serum samples were collected at 6, 14, 22 and 54 weeks, before IFX infusions. IFX
      and anti-infliximab antibodies (AIA) were measured using ELISA assays. Disease
      activity was determined by PCDAI or PUCAI. RESULTS: Clinical remission, defined
      as a clinical score <10, was obtained by 76.3% of patients at week 14 and by
      73.9% at week 54. Median trough IFX concentration was higher at all time points
      in patients achieving sustained clinical remission. IFX levels during maintenance
      correlated also with C-reactive protein, albumin and fecal calprotectin. After
      multivariate analysis, IFX concentration at week 14 >3.11 MUg/ml emerged as the
      strongest predictor of sustained clinical remission. AIA concentrations were
      correlated inversely with IFX concentrations and directly with adverse reactions.
      CONCLUSIONS: Most cases of therapeutic failure were associated with low serum
      drug levels. IFX trough levels at the end of induction are associated with
      sustained long-term response.

PMID- 30211847
TI  - Direct-acting antiviral Therapy Is Safe and Effective in Pediatric Chronic
      Hepatitis C: The Public Health Perspective.
AB  - OBJECTIVES: We assessed the efficacy of decentralised public health services and
      safety of direct-acting antiviral agents (DAAs) in the treatment of pediatric CHC
      in the Mukh-Mantri Punjab Hepatitis C Relief Fund, a public-health initiative for
      prevention and control of chronic hepatitis C(CHC) in Punjab, India. METHODS:
      Consecutive children with CHC [age >=12 to <18 years; both treatment-naive (TN)
      and treatment-experienced (TE)] were enrolled. Genotyping was not recommended for
      non-cirrhotic patients and were treated with sofosbuvir (SOF)+ daclatasvir (DCV)
      for 12-weeks, while genotyping was recommended for patients with cirrhosis.
      Patients with cirrhosis and genotype (G2) were treated with SOF+DCV+ ribavirin
      (RBV) for 12 weeks, G3 with SOF+DCV+RBV for 24 weeks and G 1,4,5&6 patients were
      treated with SOF+ ledipasvir (LDV)+ RBV for 12-weeks. Treatment duration was
      increased to 24 weeks if RBV was not tolerated. RESULTS: In the first 16-months
      (18June 2016 to 31October 2017), 88 children (mean age 15.8 years;69.3.3% male,
      72.3% rural) were enrolled. The mean baseline HCV RNA log10 IU/mL was 6.0 (range,
      4.2-7.5 log10 IU/ml), 65.5% with G3, and 2(2.5%) with cirrhosis. Of 57 with
      completed treatment, SVR12 was achieved in 56 (98.2%). Unsafe medical practices
      (55.5%), IV drug abuse (11.1%) and prior surgery (2.7%) were risk-factors for
      transmission (n = 36). Comparable results were noted in G3 (SVR12, 94.3%) versus
      non-G3 (SVR-12, 100%; P = 0.073). No serious adverse effects like anemia and
      decompensation, were reported. CONCLUSION: The study demonstrates that the
      decentralized algorithm-based public-health programme can ensure high efficacy
      (SVR-12, 98.2%) and low-cost DAA based treatment of pediatric patients with CHC.

PMID- 30211848
TI  - Traumatic rectal injuries: Is the combination of computed tomography and rigid
      proctoscopy sufficient?
AB  - BACKGROUND: There are no clear guidelines for the best test or combination of
      tests to identify traumatic rectal injuries. We hypothesize that computed
      tomography (CT) and rigid proctoscopy (RP) will identify all injuries. METHODS:
      American Association for the Surgery of Trauma multi-institutional retrospective
      study (2004-2015) of patients who sustained a traumatic rectal injury. Patients
      with known rectal injuries who underwent both CT and RP as part of their
      diagnostic workup were included. Only patients with full thickness injuries
      (American Association for the Surgery of Trauma grade II-V) were included.
      Computed tomography findings of rectal injury, perirectal stranding, or rectal
      wall thickening and RP findings of blood, mucosal abnormalities, or laceration
      were considered positive. RESULTS: One hundred six patients were identified. Mean
      age was 32 years, 85(79%) were male, and 67(63%) involved penetrating mechanisms.
      A total of 36 (34%) and 100 (94%) patients had positive CT and RP findings,
      respectively. Only 3 (3%) patients had both a negative CT and negative RP. On
      further review, each of these three patients had intraperitoneal injuries and had
      indirect evidence of rectal injury on CT scan including pneumoperitoneum or
      sacral fracture. CONCLUSION: As stand-alone tests, neither CT nor RP can
      adequately identify traumatic rectal injuries. However, the combination of both
      test demonstrates a sensitivity of 97%. Intraperitoneal injuries may be missed by
      both CT and RP, so patients with a high index of suspicion and/or indirect
      evidence of rectal injury on CT scan may necessitate laparotomy for definitive
      diagnosis. LEVEL OF EVIDENCE: Diagnostic, level IV.

PMID- 30211849
TI  - To shunt or not to shunt in combined orthopedic and vascular extremity trauma.
AB  - BACKGROUND: There exists a long established but not validated practice of placing
      temporary intravascular shunts (TIVS) in cases of combined vascular and
      orthopedic extremity trauma. Though logical to prioritize blood flow, large-scale
      data to support this practice is lacking. We hypothesize that the order of repair
      yields no difference in outcomes in combined vascular and orthopedic extremity
      trauma and offer a larger-scale analysis than is previously available. METHODS: A
      retrospective chart review was conducted at six Level I trauma centers from 2004
      to 2015 comparing patients who received a TIVS during their initial surgery
      versus those who did not. Nonshunted patients were further divided into initial
      definitive vascular repair versus initial orthopedic fixation groups. Metrics
      were used to control for sampling bias while revision rate, amputation, hospital
      length of stay (HLOS), and development of thrombosis and compartment syndrome
      were used to assess outcomes. RESULTS: Of 291 total patients, 72 had TIVS
      placement, 97 had initial definitive vascular repair, and 122 had initial
      orthopedic fixation. The shunted group had a higher Abbreviated Injury Scale (3.0
      vs. 2.8 p = 0.04) and Mangled Extremity Severity Score (6.1 vs. 5.7 p = 0.006)
      and a significantly lower rate of compartment syndrome (15% vs. 34% p = 0.002).
      Among patients who developed compartment syndrome, those who were shunted were
      younger (23 vs. 35 yrs, p = 0.03) and were more likely sustain a penetrating
      injury (p = 0.007). Those receiving initial orthopedic fixation had a longer HLOS
      (HLOS >15 days in 61% vs. 38%, p = 0.049) and a higher amputation rate (20% vs.
      7%, p = 0.006) when compared with those undergoing initial definitive vascular
      repair. CONCLUSION: Lack of TIVS was associated with a significant increase in
      the development of compartment syndrome. Though it seems to have become common
      practice to proceed directly to vascular repair during the initial surgery,
      morbidity is improved with the placement of a TIVS. LEVEL OF EVIDENCE:
      Therapeutic cohort, level III.

PMID- 30211850
TI  - Trauma and emergency general surgery patients should be extubated with an open
      abdomen.
AB  - BACKGROUND: Open abdomen (OA) and temporary abdominal closure (TAC) are common
      techniques to manage several surgical problems in trauma and emergency general
      surgery (EGS). Patients with an OA are subjected to prolonged mechanical
      ventilation. This can lead to increased rates of ventilator-associated pneumonia
      (VAP). We hypothesized that patients who were extubated with an OA would have a
      decrease in ventilator hours and as a result would have a lower rate of VAP
      without an increase in extubation failures. METHODS: A retrospective review was
      performed of all trauma and EGS patients managed at our institution with OA and
      TAC from January 2014 to February 2016. Patients were divided into cohorts
      consisting of those who were successfully extubated with an OA and those who were
      not. The number of extubation events and ventilator-free hours were calculated
      for each patient. Adverse events such as the need for reintubation with an OA and
      VAP were collected. RESULTS: Fifty-two patients (20 trauma, 32 EGS) were managed
      with an OA and TAC during the study period. Twenty-five patients (6 trauma, 19
      EGS) had at least one extubation event with an OA. Median extubation events per
      patient was 3 (interquartile range, 1-5). The median ventilator-free hours for
      patients who were extubated was 101 hours (interquartile range, 39.42-260.46).
      Patients that were never extubated with an OA had higher rates of VAP (30.8% vs.
      3.8%, p = 0.01). CONCLUSION: This study provides much needed data regarding the
      feasibility of extubation in trauma and EGS patients managed with an OA and TAC.
      Benefits of early extubation may include lower VAP rates in this population.
      Plans for reexploration hinder the decision to extubate in these patients. LEVEL
      OF EVIDENCE: Therapeutic study, level IV.

PMID- 30211851
TI  - Effects of Exendin-4 on pancreatic islets function in treating hyperglycemia post
      severe scald injury in rats.
AB  - BACKGROUND: It has been established that glucagon-like peptide 1 (GLP 1) inhibits
      pancreatic beta-cell apoptosis, increases insulin secretion, and improves glucose
      tolerance in scald injury. However, the effects of Exendin-4, a long-acting
      incretin similar to GLP 1, remained unclear in severe scald injury. Hence, this
      study attempted to investigate whether Exendin-4 had similar effects by
      protecting the histology of pancreas in severely scalded rats. METHODS: One
      hundred sixty-two adult Wistar rats were equally randomized to sham burn group,
      burn group and burn with Exendin-4 treatment group. Rats were subjected to full
      skin thickness scald injuries (total body surface area: 50%) and were injected
      subcutaneously with Exendin-4 (4 MUg/kg) twice daily. The histological changes of
      islets, the apoptosis of beta cells, the amount of glucagon and insulin, and the
      concentration of plasma glucagon and insulin were observed; and the
      intraperitoneal glucose tolerance test was performed as well. RESULTS: The islets
      and beta cells were injured and the number of secretory granules decreased in the
      scalded rats, but less histopathological changes were seen in the rats treated
      with Exendin-4. The apoptosis index of treated rats was significantly lower than
      that of the scalded rats (p < 0.05). There was significant difference in beta
      cell density postinjury between the two groups (p < 0.05). More insulin and less
      glucagon in islets and plasma were found in the treated rats (p < 0.05),
      suggesting improved intraperitoneal glucose tolerance (p < 0.05) and fasting
      blood glucose (p < 0.05) in this group. CONCLUSION: Based on our previous finding
      that GLP-1 could control hyperglycemia by increasing insulin secretion and
      inhibiting beta-cell apoptosis in severe scald injuries, this study further
      confirmed that Exendin-4 could increase glycemic control following severe scald
      by preserving the histology of beta cells in pancreatic islets and inhibiting
      their apoptosis.

PMID- 30211852
TI  - Blood purification by nonselective hemoadsorption prevents death after traumatic
      brain injury and hemorrhagic shock in rats.
AB  - BACKGROUND: Patients who sustain traumatic brain injury (TBI) and concomitant
      hemorrhagic shock (HS) are at high risk of high-magnitude inflammation which can
      lead to poor outcomes and death. Blood purification by hemoadsorption (HA) offers
      an alternative intervention to reduce inflammation after injury. We tested the
      hypothesis that HA would reduce mortality in a rat model of TBI and HS. METHODS:
      Male Sprague Dawley rats were subjected to a combined injury of a controlled
      cortical impact to their brain and pressure-controlled HS. Animals were
      subsequently instrumented with an extracorporeal blood circuit that passed
      through a cartridge for sham or experimental treatment. In experimental animals,
      the treatment cartridge was filled with proprietary beads (Cytosorbents, Monmouth
      Junction, NJ) that removed circulating molecules between 5 kDa and 60 kDa. Sham
      rats had equivalent circulation but no blood purification. Serial blood samples
      were analyzed with multiplex technology to quantify changes in a trauma-relevant
      panel of immunologic mediators. The primary outcome was survival to 96 hours
      postinjury. RESULTS: Hemoadsorption improved survival from 47% in sham-treated
      rats to 86% in HA-treated rats. There were no treatment-related changes in
      histologic appearance. Hemoadsorption affected biomarker concentrations both
      during the treatment and over the ensuing 4 days after injury. Distinct changes
      in biomarker concentrations were also measured in survivor and nonsurvivor rats
      from the entire cohort of rats indicating biomarker patterns associated with
      survival and death after injury. CONCLUSION: Blood purification by nonselective
      HA is an effective intervention to prevent death in a combined TBI/HS rat model.
      Hemoadsorption changed circulating concentrations of multiple inmmunologically
      active mediators during the treatment time frame and after treatment.
      Hemoadsorption has been safely implemented in human patients with sepsis and may
      be a treatment option after injury.

PMID- 30211853
TI  - "Quadrature detection for self-mixing interferometry" by Junfeng Wu and Fengfeng
      Shu: comment.
AB  - Some comments about the recently published Optics Letters paper "Quadrature
      detection for self-mixing interferometry," by Wu and Shu, Opt. Lett.43, 2154
      (2018)OPLEDP0146-959210.1364/OL.43.002154, are provided.

PMID- 30211854
TI  - On-chip multi-stage optical delay based on cascaded Brillouin light storage.
AB  - Storing and delaying optical signals plays a crucial role in data centers, phased
      array antennas, communication, and future computing architectures. Here, we show
      a delay scheme based on cascaded Brillouin light storage that achieves multi
      stage delay at arbitrary positions within a photonic integrated circuit.
      Importantly these multiple resonant transfers between the optical and acoustic
      domain are controlled solely via external optical control pulses, allowing
      cascading of the delay without the need of aligning multiple structural
      resonances along the optical circuit.

PMID- 30211855
TI  - Effect of Tm3+ concentration on the emission wavelength shift in Tm3+-doped
      silica microsphere lasers.
AB  - In this work, a Tm3+-doped solgel silica microsphere lasing at 2.0 MUm is
      reported. Microspheres with different Tm3+ concentrations are fabricated by
      overlaying different Tm3+ concentration solgel solutions on the surface of a pure
      silica microsphere resonator and then annealing the sample with a CO2 laser.
      Based on a traditional fiber taper-microsphere coupling method, single and
      multimode microsphere lasing in the wavelength range 1.8-2.0 MUm is observed if
      an 808 nm laser diode is used as a pump source. A relatively low threshold
      pumping power of 1.2 mW is achieved using this arrangement. This solgel method
      allows for an easy varying of the Tm3+ doping concentration. The observed laser
      output shifts to longer wavelengths when the Tm3+ doping concentration increases.
      This has been explained by the larger Tm absorption at shorter wavelengths. The
      ability to fabricate solgel co-doped silica glass microlasers represents a new
      generation of low threshold and compact infrared laser sources for use as
      miniaturized photonic components for a wide range of applications, including gas
      sensing and medical surgery.

PMID- 30211856
TI  - Multi-octave supercontinuum generation in YAG pumped by mid-infrared, multi
      picosecond pulses.
AB  - High-energy, multi-octave supercontinuum (SC) generation in bulk media pumped
      with picosecond pulses in the mid-infrared, though pivotal in a myriad of
      applications, poses severe constraints due to wavelength scaling of the critical
      power criterion and the propensity to induce avalanche-ionization-seeded
      breakdown mechanisms. Here, we demonstrate a simple experimental geometry,
      relying on a very low numerical aperture for the pump pulse, and a crystal length
      commensurate with the Rayleigh length of the focusing geometry, generating a
      multi-octave, stable SC in yttrium aluminum garnet (YAG). The SC ranges from 500
      nm to 3.5 MUm (measured at -30  dB with spectral components at wavelengths up to
      4.5 MUm) when pumped by a 3 ps pulse centered at 2.05 MUm in the anomalous
      dispersion regime. We also investigate the dynamics of filament formation in this
      interaction regime by monitoring the spectral and temporal evolution of the pulse
      during its propagation through the length of the crystal.

PMID- 30211858
TI  - Amplified measurement of weak optical activity using a spin-phase-gradient beam.
AB  - Development of alternate techniques to polarimetry for the measurement of weak
      optical rotation, with improved sensitivity, is becoming increasingly important
      as one understands the role of chirality in drug design and synthesis and the
      fundamentals of chiral light-matter interaction. We demonstrate here an optical
      amplification scheme using a spin-phase-gradient beam to measure ultra-small
      optical rotation angle (4 mdeg), with a sensitivity of 220 MUdeg/MUm, due to
      dilute (mg/mL) dextro-rotatory sugar solution. A Soleil-Babinet compensator is
      used to generate a tunable spin-phase-gradient beam which enables us to achieve
      high measurement sensitivities. Theoretical formalism of the technique leads us
      to the possibility to realize much higher measurement sensitivity of up to 10
      MUdeg/MUm by tuning-in the experimental parameters.

PMID- 30211857
TI  - Integrated germanium-on-silicon Franz-Keldysh vector modulator used with a
      Kramers-Kronig receiver.
AB  - We propose an integrated vector modulator based on two compact and high-speed
      germanium-on-silicon Franz-Keldysh electro-absorption modulators. The proposed
      vector modulator is extremely compact with a total footprint of only 1800 
      MUm*200  MUm. We further experimentally demonstrate a 4-quadrature-amplitude
      modulation (4-QAM) at 40 Gb/s over a 20-km standard single-mode fiber
      transmission. The complex signal is successfully re-constructed with a single
      ended photodiode in a recently proposed Kramers-Kronig receiver for future low
      cost, low-power, and low-footprint datacenter interconnect applications. The
      preliminary performance of the vector modulator with a 16-QAM is also
      investigated.

PMID- 30211859
TI  - Tm,Ho:LiYF4 planar waveguide laser at 2.05  MUm.
AB  - The first holmium fluoride waveguide laser, to the best of our knowledge, is
      reported using a 25-MUm-thick Gd3+-ion-modified 4.5 at. % Tm3+, 0.5 at. % Ho3+
      codoped LiYF4 active layer grown by liquid phase epitaxy on (001)-oriented LiYF4
      substrate. Pumped by a Ti:sapphire laser at 797.2 nm, the planar waveguide laser
      generates 81 mW of continuous-wave (CW) output at ~2051  nm with a slope
      efficiency of 24%. Power scaling up to 186 mW at 2051 nm and 2065 nm in quasi-CW
      regime is demonstrated. The parameters of the Tm3+<->Ho3+ energy transfer are
      determined. Tm,Ho:LiYF4/LiYF4 epitaxies are promising for waveguide lasers and
      amplifiers at above 2 MUm.

PMID- 30211860
TI  - Dual modality reflection mode optical coherence and photoacoustic microscopy
      using an akinetic sensor: publisher's note.
AB  - This publisher's note corrects an error in the funding section in Opt. Lett.42,
      4319 (2017)OPLEDP0146-959210.1364/OL.42.004319.

PMID- 30211861
TI  - Sub-100  W TEM00 bulk Nd:GdVO4 oscillator based on orthogonal thermal
      compensation.
AB  - We present a Nd:GdVO4 bulk crystal oscillator with >70  WTEM00 laser output based
      on the orthogonal thermal compensation architecture. The asymmetry of thermo
      optical effects in the anisotropic crystal was well compensated for, and the
      overall thermal load was also distributed to lower the crystal temperature and
      the risk of crystal fracture. At an output coupling of 60%, a 71.2 W, TEM00 laser
      output was achieved with 44% optical efficiency. The diffraction-limited beam
      quality was measured to be Mx2=1.01 and My2=1.04 in the orthogonal directions.

PMID- 30211862
TI  - Polarization-insensitive beam splitters using all-dielectric phase gradient
      metasurfaces at visible wavelengths.
AB  - Beam splitters play important roles in several optical applications, such as
      interferometers, spectroscopy, and optical communications. In this study, we
      propose and numerically examine polarization-insensitive beam splitters utilizing
      two-step phase gradient all-dielectric metasurfaces in the visible spectrum. The
      metasurface is made of periodically arranged binary unit cells, and phase
      difference between neighboring unit cells on the surface is 180 deg. The
      metasurface is shown to have a special phase gradient whose sign changes
      periodically. The angle of the split beams on both sides and the corresponding
      total transmission value at 532 nm wavelength are found to be +/-46.8 degrees 
      and 0.90, respectively.

PMID- 30211863
TI  - Interference patterns of vortex beams based on photonic band gap structure.
AB  - We experimentally observe a vortex six-wave mixing (SWM), namely, enhanced four
      wave mixing (FWM), signal with its orbital angular momentum transferred from a
      vortex probe via a photonic band gap (PBG) structure in a hot rubidium vapor
      cell. By analyzing spatial images and interference patterns, on the one hand, we
      demonstrate spatial shift and splitting of the images as well as shift of phase
      singularity for the probe transmission signal under the nonlinear phase of
      different dressing fields; on the other hand, we observe defocusing and shift of
      the images as well as shift of phase singularity for the reflected vortex SWM
      signal by scanning the frequency detuning of a related field. Moreover, we find
      the interference patterns of the vortex probe can be switched from parallel shape
      to spiral shape by changing its incident angle. Also, we further research the
      spiral interference patterns of the transmitted signal by scanning the probe
      detuning, observing that the number of forks changes with the detuning. We
      consider the transmitted signal as a combined beam of the linear probe and
      nonlinear FWM, which are separated under Kerr effect. It is the separation that
      causes the fork number to change with probe detuning. Our studies are useful for
      better understanding and manipulation of optical vortices and have wide
      applications in quantum communication and information processing.

PMID- 30211864
TI  - Sum frequency generation of multi-line slab radio frequency discharge carbon
      monoxide laser system with intracavity nonlinear BaGa2GeSe6 crystal.
AB  - A compact repetitively pulsed broadband carbon monoxide (CO) laser system with
      intracavity frequency conversion, for which a nonlinear crystal was also used as
      an output coupler, was launched for the first time, to the best of our knowledge.
      The laser system simultaneously operated in two spectral ranges: CO laser
      fundamental band (4.9-6.0 MUm) and its sum frequencies band (2.45-2.95 MUm).
      Different designs of the laser cavity were considered. Peak powers of the
      fundamental and sum frequencies laser pulses were up to 2 kW and 10 W,
      respectively.

PMID- 30211865
TI  - High-fidelity cavity soliton generation in crystalline AlN micro-ring resonators.
AB  - Chip-scale mode-locked dissipative Kerr solitons have been realized on various
      materials platforms, making it possible to achieve a miniature, highly coherent
      frequency comb source with high repetition rates. Aluminum nitride (AlN), an
      appealing nonlinear optical material having both Kerr (chi3), and Pockels (chi2)
      effects, has immerse potential for comb self-referencing without the need for
      external harmonic generators. However, cavity soliton states have not yet been
      achieved in AlN microresonators. Here, we demonstrate mode-locked Kerr cavity
      soliton generation in a crystalline AlN microring resonator. By utilizing
      ultrafast tuning of the pump frequency through single-sideband modulation, in
      combination with an optimized wavelength scan and pump power-ramp patterns, we
      can deterministically elongate a ~400  ns short-lived soliton to a time span as
      long as we wish to hold it.

PMID- 30211867
TI  - Unusual polarizing effect of cylindrical plasmonic holes.
AB  - We observe an unusual polarization state conversion in the light that passes
      through a cylindrical hole in a thick metal film. This phenomenon is related to
      the helicity locking of the guided mode due to the plasmonic transverse spin-an
      intrinsic angular momentum of the surface waves. We show how this effect is
      linked to the generation of the plasmonic vortex inside the hole and can be
      altered by varying the hole diameter. In addition, the total light transmission
      through the hole is shown to be partially contributed from the direct
      transmission, which can further modify the resulting light polarization state.

PMID- 30211866
TI  - Assessing patterns for compressive fluorescence lifetime imaging.
AB  - A novel hyperspectral single pixel system was used to compare different
      compressive basis patterns for intensity imaging, lifetime imaging, and FRET
      quantification. Six popular basis patterns were compared experimentally in a
      phantom containing two fluorescent dyes. The basis patterns that performed best
      for lifetime quantification were used to measure FRET occurrence in well-plate
      samples with varying acceptor-donor ratios. The ABS-WP approach using Haar
      patterns and the compressive sensing approach with Hadamard Ranked patterns
      displayed the best overall performances at a 50% compression ratio.

PMID- 30211868
TI  - Graphene-based all-optical multi-parameter regulations for an ultrafast fiber
      laser.
AB  - Ultrafast lasers with tunable capabilities of pulse duration and spectrum have
      widespread applications in telecommunication, spectroscopy, and nonlinear optical
      bio-imaging. However, traditional mechanical and electrical tuning methods are
      still challenging for precise and stable controlling. Based on graphene's photo
      thermal effect, we tune the bandwidths and wavelengths of chirped fiber Bragg
      gratings with flexible graphene-coating approaches. By inserting the fabricated
      devices into an ultrafast fiber laser cavity, durations and wavelengths of the
      generated pulses can be all-optically tuned with sensitivities of 470 fs/mW and
      2.9 pm/mW, separately. Such an optical-controlled method provides a compact and
      precise way to regulate various laser properties.

PMID- 30211869
TI  - Timing jitter of high-repetition-rate mode-locked fiber lasers.
AB  - We characterize the timing jitter of the pulse trains from 880 MHz Yb-doped
      nonlinear polarization rotation mode-locked fiber lasers based on a balanced
      optical cross-correlation method. Jitter spectral density at different net-cavity
      dispersions has been characterized, and the near-zero dispersion shows the lowest
      rms timing jitter (10 fs rms, integrated from 30 kHz to 5 MHz). The measurements
      have been compared with analytical models. The comparison shows that the RIN
      coupled timing jitter by nonlinearity is the dominated origin of the measured
      timing jitter below ~100  kHz, while amplified spontaneous emission noise makes a
      major contribution in the high frequency range above hundreds of kilohertz. To
      the best of our knowledge, this is the first high-precision timing jitter
      characterization for the ~gigahertz level repetition rate mode-locked fiber
      lasers. The results will be of great importance for further improving the laser
      performance for many applications.

PMID- 30211870
TI  - High-speed fiber scanning endoscope for volumetric multi-megahertz optical
      coherence tomography.
AB  - We present a forward-viewing fiber scanning endoscope (FSE) for high-speed
      volumetric optical coherence tomography (OCT). The reduction in size of the probe
      was achieved by substituting the focusing optics by an all-fiber-based imaging
      system which consists of a combination of scanning single-mode fibers, a glass
      spacer, made from a step-index multi-mode fiber, and a gradient-index fiber. A
      lateral resolution of 11 MUm was achieved at a working distance of 1.2 mm. The
      newly designed piezo-based FSE has an outer diameter of 1.6 mm and a rigid length
      of 13.5 mm. By moving the whole imaging optic in spirals for scanning the sample,
      the beam quality remains constant over the entire field of view with a diameter
      of 0.8 mm. The scanning frequency was adjusted to 1.22 kHz for use with a 3.28
      MHz Fourier domain mode locked OCT system. Densely sampled volumes have been
      imaged at a rate of 6 volumes per second.

PMID- 30211871
TI  - Flexoelectro-optic liquid crystal analog phase-only modulator with a 2pi range
      and 1  kHz switching.
AB  - We present a flexoelectro-optic liquid crystal (LC) analog phase modulator with
      >2pi phase range at a 1 kHz switching frequency. The chiral nematic LC mixture
      consists of the bimesogen CBC7CB with chiral dopant R5011, aligned in the uniform
      lying helix mode. The mixture exhibits >+/-pi/4 rotation of the optic axis for a
      drive voltage of +/-21.5  V (E=+/-4.5  V MUm-1). The rotation of the optic axis
      is converted into a phase modulation with the aid of a reflective device
      configuration incorporating a ~5  MUm LC cell, a polarizer, two quarter-wave
      plates, and a mirror. The residual amplitude modulation is found to be <23%. This
      flexoelectro-optic phase modulator combination has the potential to enable analog
      spatial light modulators with very fast frame rates suitable for a range of
      applications.

PMID- 30211873
TI  - 0.43  J/100  ps Nd:YAG laser with adaptive compensation of thermally induced
      lens.
AB  - We demonstrate a diode-pumped master oscillator power amplifier Nd:YAG 1064 nm
      laser with sub-joule-level output energy of 0.43 J, high pulse repetition rate of
      200 Hz, and short pulse duration of 100 ps. The 5 mJ master oscillator consisted
      of a 100 nJ/100 ps Nd:YVO4 microchip laser and end-pumped Nd:YAG regenerative
      amplifier. The two-pass output amplifier was based on two ?10*140  mm Nd:YAG
      laser rods. We apply an adaptive compensator with an analyzer based on an
      astigmatic optical system and a quadrant photodiode to compensate for low-order
      wave-front non-stationary thermal distortions in a high-energy laser amplifier.
      The adaptive compensator demonstrates high sensitivity to curvature changes of
      lambda/100, and it provides output beam divergence near 1.5*DL in 100 ps 0.43 
      J*200  Hz of operation mode.

PMID- 30211874
TI  - Characterizing d-dimensional quantum channels by means of quantum process
      tomography.
AB  - In this Letter, we propose a simple optical architecture based on phase-only
      programmable spatial light modulators, in order to characterize general processes
      on photonic spatial quantum systems in a d>2 Hilbert space. We demonstrate the
      full reconstruction of typical noises affecting quantum computing, such as
      amplitude shifts, phase shifts, and depolarizing channels in dimension d=5. We
      have also reconstructed simulated atmospheric turbulences affecting a free-space
      transmission of qudits in dimension d=4. In each case, quantum process tomography
      was performed in order to obtain the matrix chi that fully describes the
      corresponding quantum channel, E. Fidelities between the states are
      experimentally obtained after going through the channel, and the expected ones
      are above 97%.

PMID- 30211872
TI  - X-ray spectroscopy with variable line spacing based on reflection zone plate
      optics.
AB  - X-ray spectroscopy is a method, ideally suited for investigating the electronic
      structure of matter, which has been enabled by the rapid developments in light
      sources and instruments. The x-ray fluorescence lines of life-relevant elements
      such as carbon, nitrogen, and oxygen are located in the soft x-ray regime and
      call for suitable spectrometer devices. In this Letter, we present a high
      resolution spectrum of liquid water, recorded with a soft x-ray spectrometer
      based on a reflection zone plate (RZP) design. The RZP-based spectrometer with
      meridional variation of line space density from 2953 to 3757 l/mm offers
      extremely high detection efficiency and, at the same time, medium energy
      resolution. We can reproduce the well-known splitting of liquid water in the lone
      pair regime with 10 s acquisition time.

PMID- 30211875
TI  - Ultrabroadband mid-infrared noncollinear difference frequency generation in a
      silver thiogallate crystal.
AB  - We report the generation of ultrabroadband mid-infrared (mid-IR) pulses by
      noncollinear difference frequency mixing. The signal and the idler output beams
      of an optical parametric amplifier are combined in a silver thiogallate crystal
      (AgGaS2) to generate mid-infrared radiation. We show that a noncollinear geometry
      facilitates broadband phase matching. Spectral bandwidths up to 1750  cm-1 were
      obtained at an external noncollinear angle of 4.2 deg, which is more than three
      times broader than in a collinear geometry. The broadband spectrum is tunable in
      the range of 1500-4500  cm-1. Pulse energies up to 1 MUJ were achieved. The
      broadband pulses were used in sum frequency generation in ZnSe and in vibrational
      absorption spectroscopy experiments of liquid samples.

PMID- 30211876
TI  - "Terhune-like" transformation of the terahertz polarization ellipse "mutually
      induced" by three-wave joint propagation in liquid.
AB  - In this Letter, we show experimentally for the first time, to the best of our
      knowledge, the possibility to observe the effect of polarization mutual action of
      three elliptically polarized waves, with one of them at terahertz frequency, when
      they propagate in the isotropic nonlinear medium. When three light pulses are
      propagated at frequencies omega, 2omega, and omegaTHz through liquid nitrogen, we
      observed the rotation of the ellipse main axis and the ellipticity change. We
      have shown that this effect is very well described theoretically in the framework
      of a physical approach analogous to the self-rotation of the polarization ellipse
      first described in 1964 by Maker et al., but expanded for the case of multi
      frequency interaction.

PMID- 30211877
TI  - Pupil plane differential detection microscopy.
AB  - Differential interference contrast (DIC) microscopy is a powerful technique for
      imaging phase objects in transparent samples but does not work with scattering
      samples. This Letter, to the best of our knowledge, describes a new technique for
      obtaining DIC-like phase-gradient images in scattering media based on
      differential detection of forward-scattered light, using detectors arranged in a
      ring configuration around the microscope objective pupil or its conjugate pupil
      plane. This method, called pupil plane differential detection (P2D2) microscopy,
      does not need polarization optics or a confocal pinhole, yet produces images that
      are free of speckles and interference noises. We compared the P2D2 imaging
      technique with reflectance confocal microscopy and demonstrated P2D2 as a simple
      add-on to conventional laser scanning microscopes.

PMID- 30211878
TI  - Dual-view acoustic-resolution photoacoustic microscopy with enhanced resolution
      isotropy.
AB  - Acoustic-resolution photoacoustic microscopy (AR-PAM) can provide penetration
      depths beyond the optical diffusion limit, but its lateral resolution is
      typically much worse than its axial resolution, resulting in a low-resolution
      isotropy. We herein present a dual-view AR-PAM (DV-AR-PAM) system that exploits
      two orthogonally arranged focused ultrasonic transducers. Taking advantage of
      their complementary acoustic detecting profiles, DV-AR-PAM allows the fusion of
      the dual-view signals, resulting in an enhancement in the resolution isotropy
      from 29% to 95% within one imaging plane, as demonstrated by simulation results
      on densely packed particles and experimental results on a single carbon fiber.
      The application of this method in vivo revealed distinct microvasculature
      structures in mouse skin that were previously indistinguishable with single-view
      detection, demonstrating the potential of DV-AR-PAM for vascular and neurological
      studies.

PMID- 30211879
TI  - alpha-In2Se3 wideband optical modulator for pulsed fiber lasers.
AB  - With the magnetron-sputtering deposition method, alpha phase indium selenide
      (alpha-In2Se3) was developed into a saturable absorber (SA) with wideband
      saturable absorption property at 800, 1560, and 1930 nm. After inserting the
      alpha-In2Se3 SA into erbium-doped fiber laser (EDFL) and thulium-doped fiber
      laser (TDFL) systems, we can easily obtain stable soliton pulse trains. The pulse
      duration/pulse energy/slope efficiency for EDFL and TDFL were 276 fs/2.03
      nJ/15.8% and 1.02 ps/7.1 nJ/23.5%, respectively. These results showed that the
      MSD-grown alpha-In2Se3 could be regarded as high efficiency material to be
      applied in ultrafast photonics.

PMID- 30211880
TI  - Femtosecond laser-inscribed fiber interface Mach-Zehnder interferometer for
      temperature-insensitive refractive index measurement.
AB  - A new fiber interface Mach-Zehnder interferometer has been fabricated, to the
      best of our knowledge, in coreless fiber by femtosecond laser-inscription for
      temperature-insensitive refractive index measurement. A straight waveguide was
      inscribed along the central axis of the coreless fiber as the reference arm, and
      the other curved waveguide (interface waveguide) was then inscribed bending
      toward the cladding interface to obtain a strong evanescent field sensitive to
      ambient refractive index. This fiber interface Mach-Zehnder interferometer
      exhibits a high refractive index (RI) sensitivity of ~3000  nm/RIU at an RI value
      of 1.432. Moreover, with the significant advantages of high mechanical strength
      and temperature independence, such a fiber Mach-Zehnder interferometer may find
      many potential applications in biochemical sensing.

PMID- 30211881
TI  - Multi-channel velocity multiplexing of single virus detection on an optofluidic
      chip.
AB  - Liquid-core waveguide-based optofluidic devices have proven to be valuable tools
      for analysis of biological samples in fluid. They have enabled single bioparticle
      sensitivity while maintaining in-plane detection via light-induced fluorescence.
      The incorporation of multi-spot excitation with multimode interference (MMI)
      waveguides has enabled spatially and spectrally multiplexed detection of single
      viruses on an oxide-based optofluidic platform. Here, we introduce a new way of
      MMI-based multiplexing where multiple analysis channels are placed within a
      single multi-spot pattern. This stacked channel design enables both velocity and
      spectral multiplexing of single particles. The principle is demonstrated with
      differentiated detection of single H3N2 and H1N1 viruses on a
      polydimethylsiloxane platform.

PMID- 30211882
TI  - One-volt silicon photonic crystal nanocavity modulator with indium oxide gate.
AB  - The ever-increasing global network traffic requires a high level of seamless
      integration between optical interconnect systems and complementary metal-oxide
      semiconductor (CMOS) circuits. Therefore, it brings stringent requirements for
      future electro-optic (E-O) modulators, which should be ultracompact, energy
      efficient, high bandwidth, and in the meanwhile, able to be directly driven by
      the state-of-the-art CMOS circuits. In this Letter, we report a low-voltage
      silicon photonic crystal nanocavity modulator using an optimized metal-oxide
      semiconductor (MOS) capacitor consisting of an In2O3/HfO2/p-Si stacked
      nanostructure. The strong light-matter interaction from the accumulated free
      carriers with the nanocavity resonant mode results in holistic improvement in
      device performance, including a high tuning efficiency of 250 pm/V and an average
      modulation strength of 4 dB/V with a moderate Q factor of ~3700 and insertion
      loss of ~6  dB using an ultrashort electrode length of only 350 nm. With 1 V
      driving voltage over a capacitive loading of only 13 fF, the silicon photonic
      nanocavity modulator can achieve more than 3 dB extinction ratio with energy
      consumption of only 3 fJ/bit. Such a low-voltage, low-capacitance silicon
      nanocavity modulator provides the feasibility to be directly driven by a CMOS
      logic gate for single-chip integration.

PMID- 30211883
TI  - Extension of water-window harmonic cutoff by laser defocusing-assisted phase
      matching.
AB  - We extend a recently demonstrated scheme [Optica4, 976 (2017)OPTIC82334
      253610.1364/OPTICA.4.000976] to overcome the limit of conventional harmonic
      cutoff for different pulse durations, laser wavelengths, and gas targets. By
      tuning the truncation of long wavelength lasers, we show that the defocusing
      assisted phase matching (DAPM) can be achieved in a tightly focused beam and
      highly ionized short gas cell, and can be used to effectively extend the harmonic
      cutoff energy and optimize its yield. An analysis of phase matching reveals that
      at longer wavelengths, greater cutoff extension to the water window region is
      achieved because of the larger harmonic intrinsic phase (proportional to the cube
      of laser wavelength), and because DAPM works at relatively higher laser
      intensities using a Ne target. This scheme provides a promising method for
      efficiently generating intense attosecond light sources in the extreme
      ultraviolet to x-rays.

PMID- 30211884
TI  - Intensity fluctuation-invariant maximum likelihood estimation of speckle order.
AB  - We present a speckle order estimation method invariant to mean intensity
      variations inside the sample. It is based on the acquisition of two statistically
      independent speckle images. The Cramer-Rao lower bound and the maximum likelihood
      estimator in the presence of pure speckle noise are derived and shown to have
      performance very close to classical estimation methods that are not invariant to
      mean intensity fluctuations. This method is also shown to be robust to Poisson
      shot noise and additive noise, and is validated on an optical experiment with a
      standard camera. Thus, it is useful for estimating speckle order in real-world
      coherent images.

PMID- 30211885
TI  - Thulium-doped nonlinear fiber amplifier delivering 50  fs pulses at 20  W of
      average power.
AB  - In this Letter, we present an optimized nonlinear amplification scheme in the 2
      MUm wavelength region. This laser source delivers 50 fs pulses at an 80 MHz
      repetition rate with exceptional temporal pulse quality and 20 W of average
      output power. According to predictions from numerical simulations, it is
      experimentally confirmed that dispersion management is crucial to prevent the
      growth of side pulses and an increase of the energy content in a temporal
      pedestal surrounding the self-compressed pulse. Based on these results, we
      discuss guidelines to ensure high temporal pulse quality from nonlinear
      femtosecond fiber amplifiers in the anomalous dispersion regime.

PMID- 30211886
TI  - Twisted tilted fiber Bragg gratings: new structures and polarization properties.
AB  - In this Letter, it has been shown that the twisting of TFBGs (tilted fiber Bragg
      gratings) decreases their sensitivity to the polarization of the input light. It
      has been proved by a theoretical simulation study that twisting the TFBG by 180
      degrees  eliminates the sensitivity of the grating to input light polarization
      changes. We have experimentally proved that our structure produced has an 18
      times lower coefficient of variation of transmission for polarization changes
      than the untwisted TFBG. This Letter also presents a new method for manufacturing
      the twisted tilted fiber Bragg grating (TTFBG). We have demonstrated the
      possibility of writing the TTFBG structure twisted by 90 degrees  on a fiber with
      a length of 10 mm. The structure has been further twisted in the other direction
      by 90 degrees , which is consistent with a structure twisted by 180 degrees . The
      properties of both structures were determined. Due to the fiber's strength, the
      TTFBG twisted by 180 degrees  has to be 2 cm long. An advantage of the proposed
      method of producing the TTFBG is that there is a twist of the structure itself
      after fabrication. This creates new possibilities of using the structure in many
      applications. This type of grating can be used to reduce the sensitivity to
      polarization in various sensing applications, in particular, to measure the
      refractive index. In addition, a 180 degrees  twisted TTFBG has properties of
      direction discrimination in twist sensing applications.

PMID- 30211888
TI  - Hilbert transform-based single-shot plasmon microscopy.
AB  - The localized properties of surface plasmons (SPs) and surface waves can be
      measured with a modified confocal microscope. An interference signal arises from
      a locally generated reference close to normal incidence and the beam that forms
      the surface wave. A spatial light modulator can impose different phase shifts on
      the part of the incident light to recover the properties of the SP. We report a
      Hilbert transform method to recover the wavenumber with a single shot. The method
      is faster and potentially less expensive than previous approaches. The signal-to
      noise ratio is equivalent to the phase-stepping method. The signal processing
      necessary to condition the signal is described.

PMID- 30211887
TI  - Selective generation of Kerr combs induced by asymmetrically phase-detuned dual
      pumping of a fiber ring cavity.
AB  - We numerically and experimentally investigate the asymmetrically phase-detuned
      dual pumping of a passive inhomogeneous fiber ring cavity. This configuration
      originates from the fine control of frequency mismatch between the frequency
      spacing of the bichromatic pump and the free spectral range of the cavity.
      Multicomb states at offset frequencies can be selectively generated by means of
      the mismatch parameter and the coexistence of Turing and Faraday instabilities.

PMID- 30211889
TI  - Asymmetric localization induced by non-Hermitian perturbations with PT symmetry
      in photonic lattice.
AB  - We study both theoretically and numerically the asymmetric localization of
      lightwave in a three-layered photonic lattice with non-Hermitian perturbations.
      The results indicate that the gauge potential for photons can arise from the non
      Hermitian perturbations, once the perturbations satisfy parity-time symmetry.
      Further study shows that the Peierls phase between adjacent waveguides has an
      important impact on the shapes of the band structures, which result in asymmetric
      localization of a lightwave in such a system when the wave number and Peierls
      phase satisfy k=phi=+/-pi/2. This Letter provides a new way to control the light
      transmission and a feasible method to realize gauge potential for photons.

PMID- 30211890
TI  - Reconfigurable RGB dye lasers based on the laminar flow control in an optofluidic
      chip.
AB  - The optofluidic dye laser serves as an important on-chip optical source in
      microfluidic technology for a breadth of applications. One of the ultimate goals
      of such a light source is an optofluidic white dye laser. However, realizing such
      a device has been challenging, because it is difficult to achieve simultaneous
      multi-wavelength lasers that span the most visible spectrum, especially on an
      integrated system. Here, we demonstrate white lasing in an optofluidic chip that
      simultaneously lases in red, green, and blue (RGB) colors inside a microfluidic
      channel. A Fabry-Perot cavity formed by two end-coated fibers provides the
      optical feedback of the laser. Easy reconfigurable emission can be obtained based
      on the laminar flow control. Eventually, white lasing at a low threshold was
      obtained when the pumping energy density is in excess of 26.1  MUJ/mm2.

PMID- 30211891
TI  - Sub-wavelength field enhancement in the mid-IR: photonics versus plasmonics
      versus phononics.
AB  - The ability to concentrate the electrical field into sub-wavelength volumes is a
      key benefit sought and, to a certain degree, found within the discipline of
      plasmonics. This ability is restricted only by the ohmic loss in noble metals
      and, recently, in the infrared region, metals are beginning to face a challenge
      from emerging alternative media: phononic (i.e., relying on surface phonon
      polaritons) and photonic (i.e., relying on high refractive index) all-dielectric
      structures, and highly doped semiconductors, all of them having smaller intrinsic
      loss than metals. In this Letter, we compare the degree of enhancement and its
      spectral selectivity for different media and confirm that, while one can obtain
      sharper resonant features with all-dielectric structures, the magnitude of the
      field enhancement is invariably higher with metals such as gold and copper,
      primarily due to a higher density of electrons. On the whole, depending on the
      application, metals and dielectrics have their own unique advantages.

PMID- 30211892
TI  - Optical thickness measurement with single-shot dual-wavelength in-line digital
      holography.
AB  - An algorithm for quantitative reconstruction of the optical thickness
      distribution of objects is proposed based on single-shot dual-wavelength in-line
      digital holography. Two single-wavelength holograms can be extracted from a
      single-shot recorded dual-wavelength in-line hologram. The quantitative optical
      thickness distribution of the specimen can be reconstructed directly without
      calculations of the phase images at every single wavelength. Thus, off-axis
      recording and phase-shifting operation are not required, enabling a fast and high
      resolution measurement. The effectiveness and accuracy of the proposed method are
      verified by both numerical simulations and experimental results.

PMID- 30211893
TI  - External cavity type-I quantum well cascade diode lasers with a tuning range of
      440  nm near 3  MUm.
AB  - A three-stage cascade GaSb-based diode laser heterostructure with an enhanced
      optical gain spectral bandwidth was designed and fabricated. The gain broadening
      was achieved by varying the thickness of the type-I quantum wells in different
      stages of the cascade active region from 10 to 14 nm. The structures were
      processed into bent ridge gain chips with virtually eliminated feedback from the
      anti-reflection-coated angled facet. The external cavity devices based on a novel
      gain chip design demonstrated a record wide tuning range from 2.79 to 3.23 MUm in
      a Littrow cavity configuration at 20 degrees C.

PMID- 30211894
TI  - Temperature determination of superheated water vapor by rotational-vibrational
      Raman spectroscopy.
AB  - We present a novel non-invasive laser-based tool for tracer-free spatially
      resolved temperature measurement in superheated water vapor at atmospheric
      pressure. The technique exploits the temperature sensitivity of the rotational
      vibrational Raman spectrum of the v1 stretching vibration. This Letter
      demonstrates the Raman sensor, its application to a steam gasification reactor,
      and four methods to analyze the Raman spectra in order to obtain the temperature:
      an equal intensity point approach, a pseudo-isosbestic point approach, and two
      approaches based on the reconstruction of the Raman band by Gaussian/Lorentzian
      profiles. The evaluated water vapor temperatures inside a reactor for plasma
      assisted gasification are compared to data acquired by supercontinuum absorption
      spectroscopy.

PMID- 30211895
TI  - Experimental demonstration of infrared spectral reconstruction using plasmonic
      metasurfaces.
AB  - We computationally reconstruct short- to long-wave infrared spectra using an
      array of plasmonic metasurface filters. We illuminate the filter array with an
      unknown spectrum and measure the optical power transmitted through each filter
      with an infrared microscope to emulate a filter-detector array system. We then
      use the recursive least squares method to determine the unknown spectrum. We
      demonstrate our method with light from a blackbody. We also demonstrate it with
      spectra generated by passing the light from the blackbody through various
      materials. Our approach is a step towards miniaturized spectrometers spanning the
      short- to long-wave infrared based on filter-detector arrays.

PMID- 30211896
TI  - Difference frequency generation in free electron lasers.
AB  - We propose a simple scheme for difference frequency generation in free electron
      lasers (FELs), in which the electron beam interacts with a dual-frequency laser
      and emits intense coherent radiation at the difference frequency. We analytically
      show that the microbunch formation in the electron beam, which is the most
      important process in FELs, is dominated by nonlinear wave mixing in the proposed
      scheme. Numerical examples of applying the proposed scheme to generating
      terahertz radiation are presented as one of the most important applications.

PMID- 30211897
TI  - LED-pumped passively Q-switched Cr:LiSAF laser.
AB  - We report, to the best of our knowledge, the first light-emitting diode (LED)
      pumped Cr:LiSAF laser, in both quasi-continuous-wave (QCW) and passively Q
      switched operation. This Letter is based on the recent development of LED-pumped
      luminescent concentrators (LCs). Combining the capacity of high-density
      integration of blue LEDs with the excellent properties of Ce:YAG LCs, this new
      pump source can deliver high irradiance (7.3  kW/cm2) in the visible to pump
      Cr:LiSAF. The Cr:LiSAF laser demonstrates an energy of 8.4 mJ at 850 nm in QCW
      (250 MUs pulses at 10 Hz). A small signal gain per roundtrip of 1.44 at 850 nm
      and a wavelength tunability between 810 and 960 nm have been performed. A
      passively Q-switched oscillator is also presented using a Cr:YAG saturable
      absorber. A peak power of 3.1 kW is obtained with a pulse energy of 130 MUJ and
      duration of 41.6 ns.

PMID- 30211898
TI  - Single-shot noninterferometric measurement of the phase transmission matrix in
      multicore fibers.
AB  - A simple technique for far-field single-shot noninterferometric determination of
      the phase transmission matrix of a multicore fiber with over 100 cores is
      presented. This phase retrieval technique relies on the aperiodic arrangement of
      the cores.

PMID- 30211899
TI  - Enhanced performance of a reservoir computer using polarization dynamics in
      VCSELs.
AB  - We analyze the performance of a reservoir computer based on time-delay feedback
      and optical injection, which is drawing benefits from the high-speed polarization
      dynamics of a vertical cavity surface emitting laser. We show that such a system
      has high computation performance and yields deeper memory than an existing single
      mode laser-based reservoir computer. Performance is demonstrated on several
      benchmarking tasks. In particular, the error rate is an order of magnitude
      smaller when performing channel equalization.

PMID- 30211900
TI  - Near field focusing by edge diffraction: publisher's note.
AB  - This publisher's note corrects an error in the reference section of Opt. Lett.43,
      4053 (2018)OPLEDP0146-959210.1364/OL.43.004053.

PMID- 30211901
TI  - High-performance organic light-emitting photodetector fabricated by separating
      photodetective center from emissive layer without luminance trade-off.
AB  - A heterojunction consisting of poly[(9,9-dioctylfluorenyl-2,7-diyl)-alt-(4,4'-(N
      (4-butylphenyl)))] (TFB) and aluminum tris(8-hydroxyquinolinate) (Alq3) is
      applied for fabricating an organic light-emitting photodetector (OLEP), where TFB
      and Alq3 behave as an ultraviolet response center and a green light emitter,
      respectively. The OLEP shows a detectivity of 1.4*1011 Jones and a luminance of
      11,569  cd/m2. Thermal active delay fluorescent material is introduced in the TFB
      matrix to improve photodetection property. As a result, the optimized device
      exhibits a 2857% boost in a maximum detectivity of 4.0*1012 Jones without trading
      off the electroluminescence performance, exhibiting a high luminance of 13,737 
      cd/m2.

PMID- 30211902
TI  - Extreme-ultraviolet high-order harmonic generation from few-cycle annular beams.
AB  - An annular infrared (IR) laser beam has been used for high-order harmonic
      generation reaching a cut-off energy of 90 eV for extreme-ultraviolet-infrared
      (XUV-IR) pump-probe experiments in an intrinsically stable attosecond beamline.
      The generation of harmonics along the laser axis in the missing portion of the
      laser beam decreases the IR power load on thin metallic foils that are used for
      removing the residual IR and shaping the XUV pulses from high-harmonic
      generation. This finds applications in high-average-power few-cycle laser
      systems, where high-average IR power destroys the foils. The spatial separation
      of IR and XUV will, moreover, simplify the realization of attosecond time
      resolved measurements.

PMID- 30211903
TI  - Photoionization delays in xenon using single-shot referencing in the collinear
      back-focusing geometry.
AB  - Attosecond photoemission delays for all the valence (5p3/2, 5p1/2, 5s, 4d5/2,
      4d3/2) subshells of xenon have been accessed using the interferometric RABBITT
      technique. The 4d subshell delays in Xe have been accessed for the first time, to
      the best of our knowledge, due to the high photon energy used. A novel technique
      of single-shot referencing in the collinear back-focusing geometry has been
      introduced. This enables us to distinguish the signal from principal
      photoelectron peaks due to ionization by extreme ultraviolet radiation only and
      infrared-induced sideband contributions, especially in the regions of spectral
      overlap.

PMID- 30211904
TI  - Phase retardation measurement of an arbitrary wave plate based on magneto-optical
      modulating and residue detecting of the base frequency component of the signal.
AB  - Wave plates (WPs) are key components in optical polarization systems whose phase
      retardations should be measured accurately. The key point of most light
      extinction methods focuses on how to precisely judge the system's extinction
      state and then confirm corresponding angle positions of the optical components.
      Usually the extinction state of a measurement system is judged by detecting
      residue of outgoing light intensity. In this Letter, a method of measuring the
      phase retardation of an arbitrary WP based on magneto-optical modulation is
      proposed. A magneto-optical modulator is placed between the standard quarter-WP
      and the second polarizer on the basis of the traditional optical path. The
      measurement signal is obtained after the outgoing light passing through a band
      pass filter whose center frequency is the same as the frequency of the magneto
      optic modulator's driving voltage. This method detects the base frequency
      component instead of the whole intensity of the outgoing light, so as to get
      better judgement accuracy of the system's extinction state. The arbitrary WP's
      phase retardation can be accurately derived by detecting the residue of the base
      frequency component of the outgoing light signal and then judging the angle
      position of the second polarizer when the system is in the state of extinction.
      The corresponding theoretical formulas are deduced by the Jones matrix, and the
      WP measuring system is established. The error analysis shows that the system
      measurement uncertainty is about 4.5' if the experiment temperature varies in the
      range of 0.1 degrees C. Experiment results on half-WPs and quarter-WPs show that
      the presented method is in good agreement with other methods. The measurement
      repeatability is also good, with the standard deviation about 2'.

PMID- 30211905
TI  - Single-resonance silicon nanobeam filter with an ultra-high thermo-optic tuning
      efficiency over a wide continuous tuning range.
AB  - Energy-efficient tunability is highly desired for silicon photonic devices. We
      demonstrate a thermo-optic tunable filter with an ultra-high tuning efficiency
      based on a suspended photonic crystal nanobeam cavity. Attributed to the ultra
      small mode volume and free-standing waveguide structure, a tuning efficiency of
      21 nm/mW is achieved over a wide single-resonance tuning range of ~43.9  nm. The
      10%-90% switching times are 67.0 MUs and 68.8 MUs for the rising edge and the
      falling edge, respectively. The demonstrated energy-efficient tunable device can
      find applications in reconfigurable photonic integrated circuits.

PMID- 30211906
TI  - Dual-comb spectroscopy using plasmon-enhanced-waveguide dispersion-compensated
      quantum cascade lasers.
AB  - In this Letter, we report on sub-millisecond response time mid-infrared dual-comb
      spectroscopy using a balanced asymmetric (dispersive) dual-comb setup with a
      matched pair of plasmon-enhanced-waveguide dispersion-compensated quantum cascade
      lasers. The system performance is demonstrated by measuring spectra of
      Bromomethane (CH3Br) and Freon 134a (CH2FCF3) at approximately 7.8 MUm. A purely
      computational phase and timing-correction procedure is used to validate the
      coherence of the quantum cascade lasers frequency combs and to enable coherent
      averaging over the time scales investigated. The system achieves a noise
      equivalent absorption better than 1*10-3  Hz-1/2, with a resolution of 9.8 GHz
      (0.326  cm-1) and an optical bandwidth of 1 THz (32  cm-1), with an average
      optical power of more than 1 mW per spectral element.

PMID- 30211908
TI  - Experimental demonstration of a few-mode Raman amplifier with a flat gain
      covering 1530-1605  nm.
AB  - We design and experimentally demonstrate a few-mode Raman amplifier over the C+L
      band with a flat on-off gain of ~4  dB, for the first time, to the best of our
      knowledge. A state-of-the-art gain bandwidth of 75 nm (1530-1605 nm) is achieved.
      The wavelength-dependent gain for both LP01 and LP11 modes is about 0.6 dB, and
      the maximum mode-dependent gain is less than 0.3 dB. Mode-division multiplexed
      optical transmissions are performed over 75 km few-mode fiber assisted by the
      proposed Raman amplifier. Due to the low noise Raman amplification, more than 3.3
      dB optical signal-to-noise ratio enhancement has been obtained with a
      significantly improved bit-error rate of about two orders.

PMID- 30211907
TI  - Polarization-resolved strong light-matter coupling in planar GaAs/AlGaAs
      waveguides.
AB  - We study the influence of optical selection rules and polarization splittings on
      properties of exciton polaritons in a planar AlGaAs waveguide containing embedded
      GaAs quantum wells. We demonstrate that transverse electric and transverse
      magnetic modes couple differently with light- and heavy-hole quantum well
      excitons, which leads to distinct polarization splittings of the resulting
      polariton modes. The experimental data are in good agreement with modeling based
      on theoretical data for the optical selection rules for quantum well excitons.

PMID- 30211909
TI  - Learning a convolutional demosaicing network for microgrid polarimeter imagery.
AB  - We propose a polarization demosaicing convolutional neural network to address the
      image demosaicing issue, the last unsolved issue in microgrid polarimeters. This
      network learns an end-to-end mapping between the mosaic images and full
      resolution ones. Skip connections and customized loss function are used to boost
      the performance. Experimental results show that our proposed network outperforms
      other state-of-the-art methods by a large margin in terms of quantitative
      measures and visual quality.

PMID- 30211910
TI  - Laser resistance dependence of interface for high-reflective coatings studied by
      capacitance-voltage and absorption measurement.
AB  - HfO2/SiO2 bilayer coatings and multilayer high-reflection coatings without and
      with a modified co-evaporated interface (MCEI) have been prepared. An MCEI is
      designed to be evaporated at an oxygen-deficient environment to achieve higher
      absorption than the conventional discrete interface. Capacitance-voltage
      measurements and absorption measurements demonstrate that an MCEI increases the
      trap density and leads to higher absorption. The laser-induced damage threshold
      and nano-indenter test results indicate that the MCEI multilayer coating exhibits
      better laser resistance and mechanical property, despite the larger absorption.
      The experimental results suggest that adhesive force between layers plays a more
      important role in nanosecond laser damage resistance than interface absorption.

PMID- 30211911
TI  - Towards power scaling of 2.8  MUm fiber lasers.
AB  - We report the demonstration of a 2824 nm passively cooled erbium-doped fluoride
      fiber laser delivering a record average output power of 41.6 W in continuous-wave
      operation. The splice-less cavity is based on intra-core fiber Bragg gratings
      written directly in the active erbium-doped fluoride fiber, which is
      bidirectionally pumped at 980 nm to reduce heat load. To the best of our
      knowledge, this result is the highest average output power achieved with a mid
      infrared fiber laser. The long-term performance of different protective endcaps
      is also investigated at high-power operation.

PMID- 30211912
TI  - Phase evolution of the direct detection noise figure of a nondegenerate fiber
      phase-sensitive amplifier.
AB  - We experimentally investigate the evolution of the direct detection noise figure
      of a nondegenerate phase-sensitive amplifier based on a nonlinear fiber, as a
      function of the relative phase between the signal, idler, and pump, all other
      parameters remaining fixed. The use of a fiber with a high stimulated Brillouin
      scattering threshold permits us to investigate the full range of phase-sensitive
      gain and noise figure without pump dithering. Good agreement is found with
      theory, both for signal only and combined signal and idler direct detections.

PMID- 30211913
TI  - Meeting report: mobile genetic elements and genome plasticity 2018.
AB  - The Mobile Genetic Elements and Genome Plasticity conference was hosted by
      Keystone Symposia in Santa Fe, NM USA, February 11-15, 2018. The organizers were
      Marlene Belfort, Evan Eichler, Henry Levin and Lynn Maquat. The goal of this
      conference was to bring together scientists from around the world to discuss the
      function of transposable elements and their impact on host species. Central
      themes of the meeting included recent innovations in genome analysis and the role
      of mobile DNA in disease and evolution. The conference included 200 scientists
      who participated in poster presentations, short talks selected from abstracts,
      and invited talks. A total of 58 talks were organized into eight sessions and two
      workshops. The topics varied from mechanisms of mobilization, to the structure of
      genomes and their defense strategies to protect against transposable elements.

PMID- 30211914
TI  - First international workshop on human endogenous retroviruses and diseases, HERVs
      & disease 2015.
AB  - The First International Scientific Conference on Human Endogenous Retroviruses
      (HERVs) and Disease, Lyon-France, May 26-27th 2015, brought together scientific
      and medical specialists from around the world investigating the involvement of
      human endogenous retroviruses (HERVs) in complex human diseases.

PMID- 30211915
TI  - Recent progress and developments of iridium-based compounds as probes for
      environmental analytes.
AB  - Metal complexes based on iridium metal centers have attracted attention as probes
      due to their tunable biological and chemical characteristics. This review
      highlights recent examples of iridium-based compounds that have been developed as
      probes for various environmental analytes. We also discuss the further challenges
      to be overcome for this class of probes in the future.

PMID- 30211916
TI  - Catalysis for the synthesis of methacrylic acid and methyl methacrylate.
AB  - Methyl methacrylate (MMA) is a specialty monomer for poly methyl methacrylate
      (PMMA) and the increasing demand for this monomer has motivated industry to
      develop clean technologies based on renewable resources. The dominant commercial
      process reacts acetone and hydrogen cyanide to MMA (ACH route) but the
      intermediates (hydrogen cyanide, and acetone cyanohydrin) are toxic and represent
      an environmental hazard. Esterification of methacrylic acid (MAA) to MMA is a
      compelling alternative together with ethylene, propylene, and isobutene/t-butanol
      as feedstocks. Partially oxidizing isobutane or 2-methyl-1,3-propanediol (2MPDO)
      over heteropolycompounds to MAA in a single-step is nascent technology to replace
      current processes. The focus of this review is on catalysts and their role in the
      development of processes herein described. Indeed, in some cases remarkable
      catalysts were studied that enabled considerable steps forward in both the
      advancement of catalysis science and establishing the basis for new technologies.
      An emblematic example is represented by Keggin-type heteropolycompounds with
      cesium and vanadium, which are promising catalysts to convert isobutane and 2MPDO
      to MAA. Renewable sources for the MMA or MAA route include acetone, isobutanol,
      ethanol, lactic, itaconic, and citric acids. End-of-life PMMA is expected to grow
      as a future source of MMA.

PMID- 30211917
TI  - Hydrogen bond directed aerobic oxidation of amines via photoredox catalysis.
AB  - An application of H-bonding interactions for directing the alpha-C-H oxidation of
      amines to amides and amino-ketones catalyzed by an organic photocatalyst is
      reported. The high efficiency of this method is demonstrated by the aerobic
      oxidation of pyrrolidines, diarylamines and benzylamines bearing urea groups with
      high yields and a wide substrate scope.

PMID- 30211918
TI  - First-principles study of anion diffusion in lead-free halide double perovskites.
AB  - Halide ion diffusion in organolead halide perovskites has raised great concern in
      recent years and been considered as the reason for the hysteresis of current
      voltage curves and degradation of perovskite solar cells. In this work, X-site
      halide ion diffusion in lead-free double perovskites Cs2AgBiX6 (X = Cl, Br),
      Cs2AgSbCl6 and Cs2AgInCl6 is investigated by first-principles calculations. The
      formation energies of X-site vacancies are calculated for these double
      perovskites, and predicted to be related to the electronic configurations of B
      site cations. Cs2AgInCl6 is found to have the lowest vacancy formation energy
      among these double perovskites due to the unfilled s-orbitals of In3+. Using the
      climbing-image nudged elastic band method, these double perovskites are found
      with different barriers for halide ion migrations around Ag- and BIII-octahedrons
      due to different migration bottleneck radii and B-X bond characters. In our
      calculations Cs2AgBiBr6 shows the lowest energy barrier for X-site ion migration,
      which can explain the phenomenon of the huge hysteresis in Cs2AgBiBr6 solar cells
      reported. These results reveal X-site vacancy formation and diffusion properties
      in these lead-free halide double perovskites, which could be useful theoretical
      support for their optoelectronic application.

PMID- 30211919
TI  - Improved luminescence and energy-transfer properties of Ca14Al10Zn6O35:Ti4+,Mn4+
      deep-red-emitting phosphors with high brightness for light-emitting diode (LED)
      plant-growth lighting.
AB  - For plant-growth lighting, novel deep-red emission phosphors with high brightness
      were obtained by co-doping Ti4+ and Mn4+ into a Ca14Al10Zn6O35 substrate through
      a conventional solid-state reaction strategy. The nominal Ca14-(x+y)/2Al10-x
      yZn6O35:xTi4+,yMn4+ (CAZO:Ti4+,Mn4+) phosphors could be excited by both near
      ultraviolet (NUV) and blue-light-emitting diode (LED) chips efficiently and
      exhibited a strong deep-red emission band ranging from 650 nm to 750 nm, which
      should be the result of the 2E -> 4A2 transition inside the [MnO6]8- octahedral.
      Multiple energy transfer from Ti4+ to Mn4+ was detected in this CAZO; whereby
      Ti4+ and Mn4+ phosphors were verified to be a result of the dipole-dipole
      interaction under excitation at 270 nm. LED plant-growth lights were fabricated
      using the as-prepared nominal Ca13.825Al9.65Zn6O35:0.15Mn4+,0.2Ti4+,0.005H3BO3
      (CAZO:Mn4+,Ti4+,H3BO3) phosphors pumped by a 460 nm blue-chip; this luminaire
      could be used to greatly promote the cultivation of succulent plants. Combined
      with the attractive thermal stability as well as high quantum efficiency (QE) of
      this phosphor, it was demonstrated that these novel phosphors may be candidate
      deep-red luminescent materials for LED plant lighting.

PMID- 30211920
TI  - TD DFT insights into unusual properties of excited sandwich complexes: structural
      transformations and vibronic interactions in Rydberg-state bis(eta6
      benzene)chromium.
AB  - Sandwich compounds represent the only class of organometallics revealing vibronic
      structures of Rydberg transitions in their gas-phase absorption and ionization
      spectra. This provides rare possibilities of verifying computational results for
      Rydberg-state metal complexes by comparison with experimental spectroscopic data.
      In this work, the lowest Ryberg p state of bis(eta6-benzene)chromium (1)
      corresponding to the 3dz2-> R4px,y transition has been modeled for the first time
      by TD DFT. The calculations were found to be able not only to estimate the energy
      of the Rydberg excitation in the 1 molecule but also to simulate its vibronic
      structure on the basis of the Rydberg-state optimized geometries and vibrational
      frequencies. The structural transformations caused by the Jahn-Teller effect in
      the excited 1 molecule appear to differ strongly from those in the degenerate
      state benzene ion, cobaltocene or other metal-benzene complexes. The in-plane CH
      bending mode provides the main contribution to the JT distortion of the 1 excited
      state D6h structure resulting in splitting of the R4px,y state into the R4px and
      R4py components belonging to the D2h point group. The calculations predict,
      however, a fluxional 1 behavior described by the D6h symmetry. Nevertheless, the
      JT effect leads to additional allowed vibronic components of the 3dz2-> R4px,y
      transition which is clearly revealed by the TD DFT simulation. The computational
      results correlate surprisingly well with the known experimental spectroscopic
      data and provide new insights into vibronic interactions in the Rydberg-state
      sandwich molecules.

PMID- 30211921
TI  - Photochemical degradation of halogenated estrogens under natural solar
      irradiance.
AB  - Halogenated estrogens are thought to be moderately potent endocrine-disrupting
      compounds that are formed during chlorine-based wastewater disinfection processes
      and may represent a significant fraction of the total amount of estrogen
      delivered from wastewater treatment plants to receiving waters. Yet we lack key
      information about the photochemical degradation of halogenated estrogens, a
      process that has important implications for UV-based wastewater treatment and
      environmental fate modeling. To better understand halogenated estrogen
      degradation in aquatic environments, we studied the direct photolysis of 17beta
      estradiol (E2), 2-bromo-17beta-estradiol (monoBrE2), 2,4-dibromo-17beta-estradiol
      (diBrE2), and 2,4-dichloro-17beta-estradiol (diClE2) as well as the indirect
      photolysis of diBrE2 under natural solar irradiance. We found that direct
      photolysis rate constants increased with halogenation as pKa values decreased and
      molar absorptivity spectra shifted toward higher wavelengths. Compared to E2,
      quantum yields were threefold larger for monoBrE2, but 15-32% smaller for the
      dihalogenated forms. The rate of diBrE2 (pKa ~ 7.5) photolysis was strongly
      influenced by pH. At pH 7, diBrE2 degraded on minute time scales due to the large
      red-shifted molar absorptivity values and greater quantum yields of the phenolate
      form. Degradation rates were only slightly different in the presence of Suwannee
      River Humic Acid (5 mg L-1), and quenching experiments pointed to excited triplet
      state dissolved organic matter (3DOM*) as the dominant reactive intermediate
      responsible for the indirect photolysis of diBrE2. Overall, our data suggest that
      halogenated estrogens are particularly susceptible to photochemical degradation
      at environmentally relevant pH values.

PMID- 30211926
TI  - [22nd International Congress of the Polish Cardiac Society].

PMID- 30211927
TI  - Use of non-vitamin K antagonist oral anticoagulants (NOACs) in patients with
      atrial fibrillation - Messages from the 2018 EHRA.

PMID- 30211922
TI  - Tuning nuclear depolarization under MAS by electron T1e.
AB  - The Cross-Effect (CE) Dynamic Nuclear Polarization (DNP) mechanism under Magic
      Angle Spinning (MAS) induces depletion or "depolarization" of the NMR signal, in
      the absence of microwave irradiation. In this study, the role of T1e on nuclear
      depolarization under MAS was tested experimentally by systematically varying the
      local and global electron spin concentration using mono-, bi- and tri-radicals.
      These spin systems show different depolarization effects that systematically
      tracked with their different T1e rates, consistent with theoretical predictions.
      In order to test whether the effect of T1e is directly or indirectly convoluted
      with other spin parameters, the tri-radical system was doped with different
      concentrations of GdCl3, only tuning the T1e rates, while keeping other
      parameters unchanged. Gratifyingly, the changes in the depolarization factor
      tracked the changes in the T1e rates. The experimental results are corroborated
      by quantum mechanics based numerical simulations which recapitulated the critical
      role of T1e. Simulations showed that the relative orientation of the two g
      tensors and e-e dipolar interaction tensors of the CE fulfilling spin pair also
      plays a major role in determining the extent of depolarization, besides the
      enhancement. This is expected as orientations influence the efficiency of the
      various level anti-crossings or the "rotor events" under MAS. However,
      experimental evaluation of the empirical spectral diffusion parameter at static
      condition showed that the local vs. global e-e dipolar interaction network is not
      a significant variable in the commonly used nitroxide radical system studied
      here, leaving T1e rates as the major modulator of depolarization.

PMID- 30211928
TI  - Providing practical answers to practical questions for NOAC therapy.

PMID- 30211930
TI  - Complete revascularization via left snuffbox approach in a nonagenarian patient
      with acute myocardial infarction.

PMID- 30211929
TI  - Effects of trans-endocardial delivery of bone marrow-derived CD133+ cells on
      angina and quality of life in patients with refractory angina: A sub-analysis of
      the REGENT-VSEL trial.
AB  - BACKGROUND: The REGENT-VSEL trial demonstrated a neutral effect of
      transendocardial injection of autologous bone marrow (BM)-derived CD133+ in
      regard to myocardial ischemia. The current sub-analysis of the REGENT VSEL trial
      aims to assess the effect stem cell therapy has on quality of life (QoL) in
      patients with refractory angina. METHODS: Thirty-one patients (63.0 +/- 6.4
      years, 70% male) with recurrent CCS II-IV angina, despite optimal medical
      therapy, enrolled in the REGENT-VSEL single center, randomized, double-blinded,
      and placebo-controlled trial. Of the 31 patients, 16 individuals were randomly
      assigned to the active stem cell group and 15 individuals were randomly assigned
      to the placebo group on a 1:1 basis. The inducibility of ischemia, (>= one
      myocardial segment) was confirmed for each patient using Tc-99m SPECT. QoL was
      measured using the Seattle Angina Questionnaire. Each patient completed the
      questionnaire prior to treatment and at the time of their outpatient follow-up
      visits at 1, 4, 6, and 12 months after cell/placebo treatment. RESULTS: The main
      finding of the REGENT-VSEL trial sub-analysis was that transendocardial injection
      of autologous BM-derived CD133+ stem cells in patients with chronic refractory
      angina did not show significant improvement in QoL in comparison to the control
      group. Moreover, there was no significant difference between cell therapy and
      placebo in a number of patients showing improvement of at least 1 Canadian
      Cardiovascular Society class during the follow-up period. CONCLUSIONS: Intra
      myocardial delivery of autologous CD133+ stem cells is safe and feasible but does
      not show a significant improvement in the QoL or angina pectoris symptoms in
      patients with chronic myocardial ischemia.

PMID- 30211931
TI  - "Golden tube" with favorable vessel remodeling at four-year follow-up after
      bioresorbable vascular scaffold implantation for moderate to severe calcified
      lesions: Insights from intravascular imaging.

PMID- 30211932
TI  - Optimal drug-eluting stent implantation with the aid of optical coherence
      tomography in the stenotic lesion of ectatic coronary artery.

PMID- 30211933
TI  - Assessment for ambiguous angiographic finding in patient with acute myocardial
      infarction by optical coherence tomography.

PMID- 30211934
TI  - Cardiac tamponade secondary to right ventricular perforation caused by a
      temporary pacemaker lead in the course of myocardial infarction.

PMID- 30211935
TI  - A novel coronary pattern in newborn with d-transposition of the great arteries.

PMID- 30211936
TI  - Bicuspid aortic stenosis in transcatheter aortic valve replacement era: Emerging
      confusions hindering the standardization of the procedure.

PMID- 30211937
TI  - We can move forward.

PMID- 30211938
TI  - [The 2018 European Heart Rhythm Association Practical Guide on the use of non
      vitamin K antagonist oral anticoagulants in patients with atrial fibrillation:
      executive summary].
AB  - Ponizszy tekst jest streszczeniem drugiej aktualizacji oryginalnego praktycznego
      przewodnika opublikowanego w 2013 roku. Leki przeciwkrzepliwe niebedace
      antagonistami witaminy K (NOAC) stanowia cenna alternatywe dla antagonistow
      witaminy K (VKA) w zapobieganiu udarom u pacjentow z migotaniem przedsionkow (AF)
      i uznano je za leki preferowane, szczegolnie dla osob rozpoczynajacych leczenie
      przeciwkrzepliwe. Zarowno lekarze, jak i pacjenci przyzwyczajaja sie do ich
      stosowania w praktyce klinicznej, istnieje jednak wiele nierozwiazanych kwestii
      dotyczacych optymalnego stosowania tych lekow w okreslonych sytuacjach
      klinicznych. Europejskie Stowarzyszenie Zaburzen Rytmu Serca (EHRA, European
      Heart Rhythm Association) podjelo sie koordynacji opracowania jednolitego sposobu
      komunikowania sie z lekarzami na temat stosowania roznych preparatow NOAC. Grupa
      okreslila 20 tematow zawierajacych konkretne scenariusze kliniczne, w odniesieniu
      do ktorych sformulowano praktyczne wskazowki na podstawie dostepnych dowodow. Do
      problemow klinicznych naleza: 1) odpowiednia kwalifikacja pacjentow do leczenia;
      2) praktyczne schematy rozpoczynania oraz monitorowania terapii za pomoca NOAC;
      3) zagwarantowanie przestrzegania zalecen przyjmowania doustnych lekow
      przeciwkrzepliwych; 4) zmiana schematow leczenia przeciwkrzepliwego; 5)
      farmakokinetyka oraz interakcje lekowe; 6) stosowanie NOAC u osob z przewlekla
      choroba nerek i zaawansowana choroba watroby; 7) sposoby pomiaru efektu
      przeciwkrzepliwego NOAC; 8) pomiar stezenia NOAC w surowicy: rzadkie wskazania,
      srodki ostroznosci, potencjalne "pulapki"; 9) postepowanie w przypadku pomylki w
      dawkowaniu; 10) postepowanie w przypadku (podejrzenia) przedawkowania bez
      krwawienia lub badania krzepniecia wskazujace na potencjalne ryzyko krwawienia;
      11) postepowanie w przypadku krwawienia w trakcie terapii za pomoca NOAC; 12)
      postepowanie u pacjentow poddanych planowym zabiegom chirurgicznym, procedurom
      inwazyjnym czy ablacji; 13) postepowanie u pacjentow wymagajacych pilnej
      interwencji chirurgicznej; 14) pacjenci z AF oraz choroba wiencowa; 15) unikanie
      pomylek w dawkowaniu NOAC w roznych wskazaniach; 16) kardiowersja u pacjenta
      leczonego NOAC; 17) AF u pacjentow z ostrym udarem mozgu leczonych NOAC; 18) NOAC
      w sytuacjach szczegolnych; 19) leczenie przeciwkrzepliwe w przypadku AF u
      pacjentow z nowotworami zlosliwymi; 20) optymalizacja leczenia za pomoca VKA.
      Dodatkowe informacje oraz materialy do pobrania, jak rowniez karty leczenia
      przeciwkrzepliwego w kilku jezykach mozna znalezc na stronie internetowej EHRA
      (www.NOACforAF.eu).

PMID- 30211939
TI  - The continued value of risk scores in advanced heart failure.

PMID- 30211940
TI  - Mineralocorticoid receptor antagonists (MRAs): more attention required (to
      prescription)!

PMID- 30211941
TI  - Safety profile of end-stage heart failure patients implanted with left
      ventricular assist devices. Krakow two-year observational all-comers study on
      left ventricular assist device recipients.

PMID- 30211942
TI  - Similar prevalence of platelet factor 4/heparin immunoglobulin G antibodies in
      patients following cardiac surgery and other patients suspected of heparin
      induced thrombocytopaenia.

PMID- 30211943
TI  - Arteriovenous fistula imitating myocardial ischaemia on electrocardiogram.

PMID- 30211944
TI  - Percutaneous mitral and tricuspid valve repair using edge-to-edge technique.

PMID- 30211945
TI  - Hybrid ablation in a patient with persistent, long-standing atrial fibrillation
      after left-sided pneumonectomy.

PMID- 30211946
TI  - The usefulness of positron emission tomography/computed tomography with 18F
      fluorodeoxyglucose in the diagnosis of cardiac device-related infective
      endocarditis.

PMID- 30211947
TI  - Successful anti-tachycardia pacing of a temporary implantable cardioverter
      defibrillator used in the treatment of an arrhythmic storm.

PMID- 30211950
TI  - A Supplement to TRANSFUSION Abstract Presentations from the AABB Annual Meeting
      Boston, MA, October 13-16, 2018.

PMID- 30211948
TI  - Successful treatment of intermediate-high-risk pulmonary embolism with aspiration
      thrombectomy: first experience in Poland.

PMID- 30211949
TI  - Defects in ribosome function delay the initiation of chromosome replication in
      Escherichia coli.
AB  - The Sra protein is a component of the 30S ribosomal subunit while RimJ is a
      ribosome-associated protein that plays a role in the maturation of the 30S
      ribosomal subunit. Here we found that Deltasra and DeltarimJ cells showed a
      delayed initiation of DNA replication, prolonged doubling time, decreased cell
      size, and decreased amounts of total protein and DnaA per cell compared with
      these observed for wild-type cells. A temperature sensitivity test demonstrated
      that absence of the Sra or RimJ protein did not change the temperature
      sensitivity of the dnaA46, dnaB252, or dnaC2 mutants. Moreover, ectopic
      expression of Sra reversed the mutant phenotype while cells carrying the pACYC177
      rimJ plasmid did not reverse the rimJ mutant phenotype. The results indicate that
      deletion of sra or rimJ cause defects in ribosomal function and affect the
      translation process, leading to a decrease in synthesis of proteins including
      DnaA. Therefore, we conclude that Sra- and RimJ-mediated ribosomal function is
      required for precise timing of initiation of chromosome replication.

PMID- 30211951
TI  - Fiber-Rich Food Processing Byproducts Enhance the Expansion of Cornstarch
      Extrudates.
AB  - : Expansion characteristics of cornstarch-based extrudates incorporating fiber
      rich food processing byproducts was explored. Waxy and regular cornstarch were
      used as the base materials with apple pomace and sugarcane bagasse incorporated
      at two addition levels (0%, 15%, and 30% w/w). Extrusions were conducted at three
      different screw speeds (150, 200, and 250 rpm) with other parameters optimized
      and kept constant. Apple pomace inclusion resulted in higher initial expansion
      index (4.23 to 5.60) and higher stable expansion index (2.76 to 4.43), but also
      showed higher shrinkage (8.50% to 34.72%) than sugarcane bagasse extrudates at
      the same inclusion levels. Inclusion of apple pomace showed potential of
      producing extrudates with significantly higher expansion than cornstarch control,
      with relatively lower energy inputs. Extrusion methods used here have the
      potential to preserve the textural quality and nutritional value of the fiber
      enriched extrudates, providing the base for healthier snack food items. PRACTICAL
      APPLICATION: Findings from this study can be extended to the other fiber-rich
      food processing byproducts, such as other fruit and vegetable pomace, cereal
      brans, and pulse hulls among other materials. This data will help the development
      of fiber-enriched extruded snacks that would have favorable consumer traits.

PMID- 30211952
TI  - Methods for blood loss estimation after vaginal birth.
AB  - BACKGROUND: Almost 358,000 women die each year in childbirth, mainly in low
      income countries. More than half of all maternal deaths occur within 24 hours of
      giving birth; severe bleeding in the postpartum period is the single most
      important cause. Depending on the rate of blood loss and other factors, such as
      pre-existing anaemia, untreated postpartum haemorrhage (PPH) can lead to
      hypovolaemic shock, multi-organ dysfunction, and maternal death, within two to
      six hours.This review investigated different methods for estimating blood loss.
      The most common method of measuring blood loss during the third stage of labour
      is visual estimation, during which the birth attendant makes a quantitative or
      semi-quantitative estimate of the amount of blood lost. In direct blood
      collection, all blood lost during the third stage of labour (except for the
      placenta and membranes) is contained in a disposable, funnelled, plastic
      collector bag, which is attached to a plastic sheet, and placed under the woman's
      buttocks. When the bleeding stops, there are two options: the bag can be weighed
      (also called gravimetric technique), or the bag can be calibrated, allowing for a
      direct measurement. A more precise measurement of blood loss is haemoglobin
      concentration (Hb) in venous blood sampling and spectrophotometry. With the dye
      dilution technique, a known quantity of dye is injected into the vein and its
      plasmatic concentration is monitored after the uterus stops bleeding. Using
      nuclear medicine, a radioactive tracer is injected, and its concentration is
      monitored after the uterus stops bleeding. Although hypothetically, these
      advanced methods could provide a better quantification of blood loss, they are
      difficult to perform and are not accessible in most settings. OBJECTIVES: To
      evaluate the effect of alternative methods to estimate blood loss during the
      third stage of labour, to help healthcare providers reduce the adverse
      consequences of postpartum haemorrhage after vaginal birth. SEARCH METHODS: We
      searched Cochrane Pregnancy and Childbirth's Trials Register (2 February 2018),
      ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform
      (ICTRP; 21 March 2018), and reference lists of retrieved studies. SELECTION
      CRITERIA: All randomised trials, including cluster-randomised trials, evaluating
      methods for estimating blood loss after vaginal birth. DATA COLLECTION AND
      ANALYSIS: Two review authors independently assessed trials for inclusion and risk
      of bias, extracted data, and checked them for accuracy. MAIN RESULTS: The search
      retrieved 62 reports in total. Of these, we assessed 12 reports in full,
      corresponding to six trials. We included three trials and excluded one; two
      trials are ongoing.The included trials were conducted in hospital settings. Two
      trials were conducted in India; the third trial was a large cluster-randomised
      trial, which took place in 13 European countries. Overall, we judged the included
      trials to be at a low risk of bias. One study evaluated the use of calibrated
      drapes versus visual estimation, another evaluated the use of calibrated drapes
      versus the gravimetric technique (weight of blood-soaked materials), therefore,
      we were unable to pool the data from the two studies. The third study did not
      measure any of the outcomes of interest, so did not contribute data to the
      analyses.Direct measurement using calibrated drapes versus visual estimationOne
      cluster-randomised controlled trial in 13 western European countries, with over
      25,000 women, examined this comparison.The trial did not report on postpartum
      anaemia (defined as Hb lower than 9 mg/dL), blood loss greater than 500 mL, or
      maternal infection.Moderate-quality evidence suggests there is probably little or
      no difference between groups in: severe morbidity (coagulopathy, organ failure,
      intensive care unit admission; adjusted risk ratio (RR) 0.82, 95% confidence
      interval (CI) 0.48 to 1.39); the risk of blood transfusion (adjusted RR 0.82, 95%
      CI 0.46 to 1.46); the use of plasma expanders (adjusted RR 0.77, 95% CI 0.42 to
      1.42); and the use of therapeutic uterotonics (adjusted RR 0.87, 95% CI 0.42 to
      1.76).Direct measurement using calibrated drapes (Excellent BRASSS-V DrapeTM)
      versus gravimetric techniqueOne randomised controlled trial in India, with 900
      women, examined this comparison.The trial did not report on postpartum anaemia
      (defined as Hb lower than 9 mg/dL), severe morbidity, or maternal infection.High
      quality evidence showed that using calibrated drapes improved the detection of
      blood loss greater than 500 mL when compared with the gravimetric technique (RR
      1.86, 95% CI 1.11 to 3.11). Low-quality evidence suggests there may be little or
      no difference in the risk of blood transfusion between the two groups (RR 1.00,
      95% CI 0.06 to 15.94), or in the use of plasma expanders, reported as intravenous
      fluids given for PPH treatment (RR 0.67; 95% CI 0.19 to 2.35). High-quality
      evidence showed little or no difference in the use of therapeutic uterotonics (RR
      1.01, 95% CI 0.90 to 1.13), but the use of therapeutic uterotonics was extremely
      high in both arms of the study (57% and 56%). AUTHORS' CONCLUSIONS: Overall, the
      evidence in this review is insufficient to support the use of one method over
      another for blood loss estimation after vaginal birth. In general, the quality of
      evidence for our predefined outcomes ranged from low to high quality, with
      downgrading decisions due to imprecision. The included trials did not report on
      many of our primary and secondary outcomes.In trials that evaluate methods for
      estimating blood loss during vaginal birth, we believe it is important to measure
      their impact on clinical maternal and neonatal outcomes, along with their
      diagnostic accuracy. This body of knowledge needs further, well designed,
      appropriately powered, randomised controlled trials that correlate blood loss
      with relevant clinical outcomes, such as those listed in this review.

PMID- 30211953
TI  - Analysis of Arsenic Species in Processed Rice Bran Products Using HPLC-ICP-MS.
AB  - : The purpose of this study was to compare the content of arsenic species (As(V),
      monomethylarsonic acid [MMA], As(III), and dimethylarsinic acid [DMA]) in
      products, such as bran powder and tablets, using high-performance liquid
      chromatography-inductively coupled plasma mass spectrometry, and to determine the
      risk of human exposure to inorganic arsenic (iAs). The products presented As(III)
      > As(V) > DMA > MMA, at 241.03 to 579.35, 43.41 to 271.91, 15.16 to 30.43, and
      limit of quantification to 14.31 MUg/kg, respectively. The contents of arsenic
      species tended to differ among the products (P < 0.05). When the maximum level
      (0.2 mg/kg) of iAs in white rice was applied to products, it exceeded 1.4 to 3.3
      times as 284.43 to 767.10 MUg/kg. Also, if more than 109.42 g/day of rice bran
      powder product containing 767.10 MUg/kg as iAs was ingested, the provisional
      tolerable weekly intake (9.0 MUg/kg body weight/wk) was exceeded. PRACTICAL
      APPLICATION: This study could provide analysis necessary of As for defining an
      accurate risk assessment of products and tablets containing rice bran powder. In
      addition with this study, the regulations for As contents in rice bran power
      products would be set.

PMID- 30211954
TI  - Behavioral responses of two species of dolphins to novel video footage: An
      exploration of sex differences.
AB  - This study assessed the interest toward novel video clips as enrichment stimuli
      in two species of captive dolphins (Tursiops: n = 11; Steno: n = 5). Videos were
      played at underwater viewing windows while the animals were housed with
      conspecifics, and responses were subsequently analyzed based on general content
      of each novel video. Interest levels (i.e., percentage of time watching and
      behavioral rate) were compared between species and within species across video
      categories. While the varied video contexts did not produce significant
      differences among the time spent watching or behaviors observed, species
      differences and sex differences were noted. Rough-toothed dolphins displayed
      significantly more behaviors, particularly interest and bubble behaviors, than
      bottlenose dolphins, with no differences observed between the species for the
      percentage of time spent watching. Among bottlenose dolphins, males watched the
      television longer, and responded behaviorally significantly more, displaying a
      higher rate of bubble and aggressive behaviors than females. Male rough-toothed
      dolphins displayed significantly more aggressive behaviors than females, with no
      other sex differences noted. Overall, these data suggest that television may
      serve as a useful enrichment device for certain individuals and species of
      cetaceans, as well as a cognitive experimental tool, as long as sex, species, and
      individual differences are taken into consideration when interpreting results.

PMID- 30211955
TI  - HoxB8 neutrophils replicate Fcgamma receptor and integrin-induced neutrophil
      signaling and functions.
AB  - Neutrophils are short-lived, terminally differentiated leukocytes that form an
      essential part of host immunity and play a key role in acute and chronic
      inflammation. The analysis of these important cells is hindered by the fact that
      neutrophils are not amenable to culture, transfection, or transduction.
      Conditionally HoxB8-immortalized mouse hematopoietic progenitors are suitable for
      in vitro differentiation of a range of myeloid cells, including neutrophils.
      Integrins and FcgammaRs are cell surface receptors, the ligation of which is
      required for a range of neutrophil functions that are important in health and
      disease. We show here that HoxB8 neutrophils express major neutrophil integrins
      and FcgammaRs. They respond to FcgammaR and integrin stimulation in a manner that
      is comparable with primary neutrophils, in terms of intracellular signaling.
      HoxB8 neutrophils also perform a range of FcgammaR/integrin-dependent neutrophil
      functions, including, generation of reactive oxygen species, degranulation, and
      chemotaxis. Our findings suggest that HoxB8 neutrophils represent a faithful
      experimental model system for the analysis of Fc and integrin receptor-dependent
      neutrophil functions.

PMID- 30211956
TI  - Comparative analyses of CTX prophage region of Vibrio cholerae seventh pandemic
      wave 1 strains isolated in Asia.
AB  - Vibrio cholerae O1 causes cholera, and cholera toxin, the principal mediator of
      massive diarrhea, is encoded by ctxAB in the cholera toxin (CTX) prophage. In
      this study, the structures of the CTX prophage region of V. cholerae strains
      isolated during the seventh pandemic wave 1 in Asian countries were determined
      and compared. Eighteen strains were categorized into eight groups by CTX prophage
      region-specific restriction fragment length polymorphism and PCR profiles and the
      structure of the region of a representative strain from each group was determined
      by DNA sequencing. Eight representative strains revealed eight distinct CTX
      prophage regions with various combinations of CTX-1, RS1 and a novel genomic
      island on chromosome I. CTX prophage regions carried by the wave 1 strains were
      diverse in structure. V. cholerae strains with an area specific CTX prophage
      region are believed to circulate in South-East Asian countries; additionally,
      multiple strains with distinct types of CTX prophage region are co-circulating in
      the area. Analysis of a phylogenetic tree generated by single nucleotide
      polymorphism differences across 2483 core genes revealed that V. cholerae strains
      categorized in the same group based on CTX prophage region structure were
      segregated in closer clusters. CTX prophage region-specific recombination events
      or gain and loss of genomic elements within the region may have occurred at much
      higher frequencies and contributed to producing a panel of CTX prophage regions
      with distinct structures among V. cholerae pathogenic strains in lineages with
      close genetic backgrounds in the early wave 1 period of the seventh cholera
      pandemic.

PMID- 30211957
TI  - Streptococcus pyogenes CAMP factor promotes calcium ion uptake in RAW264.7 cells.
AB  - Streptococcus pyogenes is a bacterium that causes systemic diseases such as
      pharyngitis and toxic shock syndrome. S. pyogenes produces molecules that inhibit
      the function of the human immune system, thus allowing growth and spread of the
      pathogen in tissues. It is known that S. pyogenes CAMP factor induces vacuolation
      in macrophages; however, the mechanism remains unclear. In the current study, the
      mechanism by which CAMP factor induces vacuolation in macrophages was
      investigated. CAMP factor was found to induce calcium ion uptake in murine
      macrophage RAW264.7 cells. In addition, EDTA inhibited calcium ion uptake and
      vacuolation in the cells. The L-type voltage-dependent calcium ion channel
      blockers nifedipine and verapamil reduced vacuolation. Furthermore, the
      phosphoinositide 3-kinase inhibitors LY294002 and wortmannin also inhibited the
      vacuolation induced by CAMP factor. Fluorescent microscopy revealed that clathrin
      localized to the vacuoles. These results suggest that the vacuolation is related
      to calcium ion uptake by RAW264.7 cells via L-type voltage-dependent calcium ion
      channels. Therefore, it was concluded that the vacuoles induced by S. pyogenes
      CAMP factor in macrophages are clathrin-dependent endosomes induced by activation
      of the phosphoinositide 3-kinase signaling pathway through calcium ion uptake.

PMID- 30211958
TI  - Granzyme B induced by Rv0140 antigen discriminates latently infected from active
      tuberculosis individuals.
AB  - Nearly two billion people are latently infected with Mtb (LTBI). Detection of
      LTBI with high risk to develop active tuberculosis (aTB) is considered the
      cornerstone to control the disease. The current challenge is to identify markers
      that better classify LTBI versus aTB. It has been previously shown that Rv0140, a
      reactivation-associated antigen of Mtb, induces significantly higher IFN-gamma
      production in LTBI individuals as compared to aTB patients. Herein, we show that
      Rv0140 induces high granzyme B level by PBMCs derived from LTBI (n = 34) as
      compared to aTB (n = 18). Receiving operator characteristic (ROC) curves were
      used to evaluate the capacity of Rv0140 to discriminate between LTBI and aTB by
      measuring IFN-gamma and granzyme B secretion. Our results show that, in response
      to Rv0140, granzyme B seems to allow better discrimination of LTBI from aTB with
      areas under the curve (AUC) of 0.88 (95% CI 0.79-0.98) as compared to IFN-gamma
      with AUC of 0.85 (95% CI 0.74-0.96) even though CI overlap. Intracellular
      staining (ICS) experiments and the use of anti-MHC I antibody showed that
      granzyme B is mainly produced by CD8+ T cells in response to Rv0140. Thus, we
      propose granzyme B as a host marker to help identify LTBI individuals.

PMID- 30211959
TI  - Stereoselective conjugate addition of ketones to alkylidene malonates using
      thiourea-sulfonamide organocatalyst.
AB  - In this study, stereoselective conjugate addition of ketones to alkylidene
      malonates using organocatalyst has been developed. The reaction in the presence
      of 20 mol% of a novel thiourea-sulfonamide organocatalyst afforded conjugate
      adducts in moderate to high yields (up to 81%) under mild reaction conditions.
      Excellent diastereoselectivity (up to 98:2 dr) and enantioselectivity (up to 88%
      ee) were achieved.

PMID- 30211960
TI  - Is Taiwan's National Health Insurance a perfect system? Problems related to
      health care utilization of the aboriginal population in rural townships.
AB  - National Health Insurance (NHI) was implemented in Taiwan in 1995, and has
      significantly increased coverage to 99% of the population. The implementation of
      NHI has had large impacts on health disparities. Despite that, the NHI faces
      multiple challenges, including the condition of "coverage without access" among
      the Taiwanese aboriginal population, mostly residing in mountainous townships and
      experiencing lower socioeconomic status, decreased health outcomes, and limited
      access to adequate high-quality health care services. This paper summarizes the
      persistent health gap and the differences in health care utilization and health
      outcomes between the aboriginal population in rural townships and urban
      populations in Taiwan. Mountainous townships face challenges including lack of
      access to high-quality health care services and limited medical resources.
      Further policy recommendations and current progress are highlighted and
      discussed.

PMID- 30211961
TI  - The need for planning training among public health officers in Cape Verde.
AB  - Cape Verde is a small island developing state (SIDS). The health sector is guided
      by strategic and programmatic documents of the Ministry of Health. The objective
      of this paper is to understand the planning capacity and experience of its Public
      Health Officers. A questionnaire was applied to 27 Cape Verdean public health
      officers in order to collect data on participation in health sector planning: 17
      were returned and analyzed. This study identifies a youthful, medically trained,
      but poorly differentiated, public health cadre, without the technical competences
      to plan the changes needed for the health sector. Planning initiatives were
      preceded by short technical planning training initiatives, but these did not
      consolidate a planning culture or contribute to a sustainable capacity to respond
      to the planning needs of the country. The respondents seemed at a loss to specify
      planning tools and techniques used in the planning exercises in which they
      partook. SIDS are considered vulnerable to political interference in the
      implementation of policy processes but that did not seem to be the case in Cape
      Verde. Planning was perceived as values driven, strengthening the perception that
      the values that drive the finality of planning are important determinants of the
      final plan.

PMID- 30211962
TI  - Sulfur-Doped CoO Nanoflakes with Loosely Packed Structure Realizing Enhanced
      Oxygen Evolution Reaction.
AB  - The development of active and inexpensive electrocatalysts for the oxygen
      evolution reaction (OER) to promote water splitting has always been a major
      challenge. Cobalt-based oxides and sulfides have been actively investigated due
      to their low cost and high activity. However, the lower intrinsic conductivity of
      cobalt oxide and the inferior stability of cobalt sulfides still limit their
      practical application. Herein, CoO was chosen for a proof-of-concept study in
      which the anion-doping strategy was used to obtain an excellent catalyst. Sulfur
      incorporation optimizes the charge-transfer properties and active sites of sulfur
      doped CoO (S-CoO) and thus gives rise to improved catalytic activity. Besides
      sulfur doping, the stable framework of the cobalt oxide was well maintained, and
      thus high stability of S-CoO throughout the reaction process was ensured.

PMID- 30211963
TI  - C2 -Symmetric Bicyclic Bisborane Catalysts: Kinetic or Thermodynamic Products of
      a Reversible Hydroboration of Dienes.
AB  - We prepared a new class of chiral C2 -symmetric bicyclic bisborane catalysts by
      addition reactions of internal dienes with the Piers borane, HB(C6 F5 )2 , and an
      analogue, HB(p-C6 F4 H)2 . The dependence of the addition pattern on the reaction
      temperature allowed us to selectively prepare two diastereomeric catalysts from a
      single diene precursor. The bisboranes prepared in situ exhibited excellent
      activity (turnover numbers up to 200 at -40  degrees C) and enantioselectivity
      (up to 95 % ee) in imine hydrogenation reactions.

PMID- 30211964
TI  - Pre-Operative Imaging for Spinal Cord Stimulation: A Case Report of a Spinal Cord
      Tumor Identified by Screening Magnetic Resonance Imaging of the Thoracic Spine.

PMID- 30211965
TI  - alpha-Borylated Phosphorus Ylides (alpha-BCPs): Electronic Frustration within a C
      B pi-Bond Arising from the Competition for a Lone Pair of Electrons.
AB  - The concept and the first example for electronic frustration within a C-B pi-bond
      arising from the competition for a lone pair of electrons is reported. The alpha
      borylated phosphorus ylide (alpha-BCP) Ph3 PC(CH3 )BEt2 (1) has been synthesized,
      characterized, and investigated with the aid of density functional theory
      calculations. These show the presence of a highly polarized C-B pi-bond, induced
      by the electron-withdrawing Ph3 P+ substituent. This competition for the C-based
      lone pair of electrons leads to an FLP-type reactivity (FLP=frustrated Lewis
      pair), which has been demonstrated by reacting 1 with various small molecules:
      the dimeric insertion products [Ph3 PC(CH3 )COBEt2 ]2 (2) and [Ph3 PC(CH3 )(CO2
      )BEt2 ]2 (5) result from the reaction of 1 with CO and CO2 , respectively,
      whereas monomeric products of the general formula [Ph3 PC(CH3 )(XYZ)BEt2 ] were
      obtained by treating 1 with COS (3), CS2 (4) or the heterocumulenes PhNCO (6) and
      PhNCS (7).

PMID- 30211966
TI  - Social cognitive abilities predict psychosocial dysfunction in major depressive
      disorder.
AB  - BACKGROUND: Major depressive disorder (MDD) is associated with social cognitive
      deficits (e.g., poor affect recognition and impaired theory of mind). However,
      the contribution of social cognitive issues to psychosocial dysfunction in MDD
      (e.g., occupational functioning and interpersonal relationships) has not been
      investigated. The current study evaluated the relationship between specific
      social cognitive domains (e.g., prosody interpretation) and psychosocial
      dysfunction in subjects with lifetime MDD, as well as currently depressed,
      remitted, and healthy controls (HCs) subjects. METHOD: Data were obtained from
      213 participants in the Cognitive Function and mood study (CoFaMS), a cross
      sectional study of mood, social cognition, cold cognition, and psychosocial
      functioning in mood disorders. Participants' (current MDD n = 42, remitted MDD n
      = 69, and HCs n = 102) social cognitive abilities were assessed using the Social
      Perception subtest of the Wechsler Adult Intelligence Scale, and psychosocial
      dysfunction was clinically evaluated with the Functioning Assessment Short Test
      (FAST). RESULTS: The results indicated that prosody interpretation, but not
      facial affect or meaning interpretation, was associated with psychosocial
      dysfunction in subjects with lifetime MDD, as well as remitted MDD subjects
      relative to HCs. In contrast, social cognition was not associated with
      functioning in participants with current MDD or in HCs. CONCLUSIONS: These
      results suggest that the relationship between social cognition and psychosocial
      functioning differs between the acute and remitted stage of illness in MDD, and
      that prosody interpretation should be considered a treatment target in patients
      with residual psychosocial issues.

PMID- 30211968
TI  - Evaluation of bone marrow microenvironment could change how myelodysplastic
      syndromes are diagnosed and treated.
AB  - Myelodysplastic syndromes are a heterogeneous group of clonal hematopoietic
      disorders. However, the therapies used against the hematopoietic stem cells
      clones have limited efficacy; they slow the evolution toward acute myeloid
      leukemia rather than stop clonal evolution and eradicate the disease. The
      progress made in recent years regarding the role of the bone marrow
      microenvironment in disease evolution may contribute to progress in this area.
      This review presents the recent updates on the role of the bone marrow
      microenvironment in myelodysplastic syndromes pathogenesis and tries to find
      answers regarding how this information could improve myelodysplastic syndromes
      diagnosis and therapy.

PMID- 30211967
TI  - Proteomic Profiling of Native Unpassaged and Culture-Expanded Mesenchymal Stromal
      Cells (MSC).
AB  - Human culture-expanded mesenchymal stromal cells (MSC) are being considered for
      multiple therapeutic applications because of their regenerative and anti
      inflammatory properties. Although a large number of MSC can be propagated from a
      small initial sample, several lines of evidence indicate that MSC lose their
      immunosuppressive and regenerative potency aftaer multiple passages. In this
      report, we use the FACSCAP Lyoplate proteomic analysis system to detect changes
      in cell surface protein expression of CD45- /CD31- /CD34- /CD73+ /CD105+ stromal
      cells in unpassaged bone marrow (BM) and through 10 serial culture passages. We
      provide for the first time a detailed characterization of native unpassaged BM
      MSC (0.08% of BM mononuclear cells) as well as the changes that occur during the
      initial expansion. Adipogenic and osteogenic differentiative potential was
      determined though the serial passages and correlated with immunophenotypic
      changes and senescence. Among the most prominent were striking decreases in Fas
      ligand, CD98, CD205, and CD106, accompanied by a gain in the expression of CD49c,
      CD63, CD98, and class 1 and class 2 major histocompatibility complex (MHC)
      molecules. Other molecules that are down-modulated with later passage include
      CD24, CD54, CD59, CD243/P-glycoprotein, and CD273/PD-L2. Early senescence, as
      defined by the loss of replicative capacity occurring with the loss of
      differentiative capacity, increase in CDKN2A p16, and increased time to
      confluence, was accompanied by loss of the motility-associated metalloproteinase
      CD10 and the proliferation-associated transferrin receptor CD71. Among the
      strongest statistical associations were loss of MAC-inhibitory protein/CD59, loss
      of ICAM-1/CD54, and increase in CDKN2A as a function of increasing passage, as
      well as increased CD10 expression with adipogenic and osteogenic capacities. The
      data provide a clear set of markers that can be used to assess MSC quality. We
      suggest that clinically relevant numbers of highly functional low passage MSC can
      be manufactured starting with large quantities of BM, which are readily available
      from cadaveric organ donors.

PMID- 30211969
TI  - In situ detection of CD73+ CD90+ CD105+ lineage: Mesenchymal stromal cells in
      human placenta and bone marrow specimens by chipcytometry.
AB  - Mesenchymal stromal cells (MSCs) support endogenous regeneration and present
      therefore promising opportunities for in situ tissue engineering. They can be
      isolated and expanded from various tissues, for example, bone marrow, adipose
      tissue, or placenta. The minimal consensus definition criteria of ex vivo
      expanded MSCs requires them to be positive for CD73, CD90, and CD105 expression,
      while being negative for CD34, CD45, CD14, CD19, and HLA-DR. This study aimed to
      compare the in situ phenotype of MSCs with that of their culture-expanded
      progeny. We report for the first time in situ detection of cells expressing this
      marker combination in human placenta cryosections as well as in bone marrow
      aspirates using multiplex-immunohistology (Chipcytometry), a technique that
      allows staining of more than 100 biomarkers consecutively on the same cell. (c)
      2018 International Society for Advancement of Cytometry.

PMID- 30211970
TI  - Improving the Design of Synthetic Oligonucleotide Probes by Fluorescence Melting
      Assay.
AB  - Nucleic acid hybridisation plays a key role in many biological processes,
      including transcription, translation, and regulation of gene expression. Several
      sophisticated applications rely on this fundamental interaction, including the
      polymerase chain reaction, sequencing, and gene therapy. To target a nucleic acid
      sequence specifically, synthetic oligonucleotides with a suitable affinity and
      specificity towards the target need to be designed. The affinity of potential
      probes or therapeutic agents to their target sequence is generally investigated
      by melting experiments, which break the hydrogen-bonding and stacking
      interactions that stabilise the double helix resulting in the formation of two
      single strands. In this paper, we report a comparative study of hybridisation for
      short fluorescent oligonucleotides labelled with cyanine and ATTO dyes, performed
      by the currently used UV melting assay and by a more sensitive fluorescence
      melting experiment. Using different oligonucleotide sequences in the
      concentration range of 5 nm to 2 MUm, we observed a stabilising effect of the
      fluorophores on the duplexes, especially at low concentrations. We paid
      particular attention to the effect of polycations and to molecular crowding as
      major parameters that define the stability and the geometry of nucleic acid
      duplexes in biological samples. We also demonstrated how the fluorometry-based
      melting data could aid the design of a probe targeting a human BRAF gene fragment
      to reduce the off-target binding by a factor of seven.

PMID- 30211971
TI  - What, where and when: spatial foraging decisions in primates.
AB  - When exploiting the environment, animals have to discriminate, track, and
      integrate salient spatial cues to navigate and identify goal sites. Actually,
      they have to know what can be found (e.g. what fruit), where (e.g. on which tree)
      and when (in what season or moment of the year). This is very relevant for
      primate species as they often live in seasonal and relatively unpredictable
      environments such as tropical forests. Here, we review and compare different
      approaches used to investigate primate spatial foraging strategies: from direct
      observations of wild primates to predictions from statistical simulations,
      including experimental approaches on both captive and wild primates, and
      experiments in captivity using virtual reality technology. Within this framework,
      most of these studies converge to show that many primate species can (i) remember
      the location of most of food resources well, and (ii) often seem to have a goal
      oriented path towards spatially permanent resources. Overall, primates likely use
      mental maps to plan different foraging strategies to enhance their fitness. The
      majority of studies suggest that they may organise spatial information on food
      resources into topological maps: they use landmarks to navigate and encode local
      spatial information with regard to direction and distance. Even though these
      studies were able to show that primates can remember food quality (what) and its
      location (where), still very little is known on how they incorporate the temporal
      knowledge of available food (when). Future studies should attempt to increase our
      understanding of the potential of primates to learn temporal patterns and how
      both socio-ecological differences among species and their cognitive abilities
      influence such behavioural strategies.

PMID- 30211972
TI  - Arabinoxylan Attenuates Type 2 Diabetes by Improvement of Carbohydrate, Lipid,
      and Amino Acid Metabolism.
AB  - SCOPE: Type 2 diabetes is a complex metabolic and endocrine disorder worldwide,
      which causes severe health and economic problems. The aim of this study is to
      investigate the molecular mechanisms by which arabinoxylan from Plantago asiatica
      L. attenuates type 2 diabetes from the perspective of urine metabolomics. METHODS
      AND RESULTS: High-fat diet and streptozotocin-induced type 2 diabetic rats are
      treated with arabinoxylan, then the urine samples are collected for untargeted
      metabolomics analysis by UPLC-Triple-TOF/MS. Diabetes causes significant
      increases in the levels of acetone, glucose, 2-oxoglutarate, and leucine, and
      significant decreases in the concentrations of creatine, histidine, lysine, l
      tryptophan, hippurate, l-cysteine, kynurenine, and arabitol as compared with
      normal rats (p < 0.01). And these 12 metabolites (with VIP cut-off value > 1) can
      be used as biomarkers in type 2 diabetes. A total of 21 urinary metabolites are
      significantly improved by arabinoxylan administration in diabetic rats, and these
      metabolites are mainly involved in TCA cycle, and metabolism of lipid and ketone
      body, taurine and hypotaurine, tryptophan, and branched chain amino acids.
      CONCLUSION: Arabinoxylan administration improves carbohydrate, lipid, and amino
      acid metabolism in type 2 diabetic rats, which provide important insights into
      the mechanisms underlying type 2 diabetes as well as the effects of arabinoxylan.

PMID- 30211973
TI  - Development and pretesting of "Becoming Breastfeeding Friendly": Empowering
      governments for global scaling up of breastfeeding programmes.
AB  - Scaling up breastfeeding programmes has not been highly prioritized despite
      overwhelming evidence that breastfeeding benefits the health of mothers and
      children. Lack of evidence-based tools for scaling up may deter countries from
      prioritizing breastfeeding. To fill this gap, Becoming Breastfeeding Friendly
      (BBF) was developed to guide countries in effectively scaling up programmes to
      protect, promote, and support breastfeeding. BBF includes an evidence-based
      toolbox that consists of a BBF Index, case studies, and a 5-meeting process.
      These three interrelated components enable countries to assess their
      breastfeeding scaling up environment, identify gaps, propose policy
      recommendations, develop a scaling up plan, and track progress. The toolbox was
      developed based on current evidence and expert guidance from a Technical Advisory
      Group, which was composed of global breastfeeding and metric experts with
      experience in the scaling up of health and nutrition programmes in low-, middle-,
      and high-income countries. The BBF toolbox required a step-by-step iterative
      approach to describe and systematize each component, thus an operational manual
      was developed. The BBF toolbox and BBF operational manual underwent intensive
      pretesting in two countries, Ghana and Mexico, resulting in the modification of
      each component plus the operational manual. Pretesting continues in six
      additional countries demonstrating that BBF is a robust and dynamic multi
      sectoral process that, with relatively minor adaptations, can be successfully
      implemented in countries across world regions.

PMID- 30211975
TI  - Object-Oriented Segmentation of Cell Nuclei in Fluorescence Microscopy Images.
AB  - Cell nucleus segmentation remains an open and challenging problem especially to
      segment nuclei in cell clumps. Splitting a cell clump would be straightforward if
      the gradients of boundary pixels in-between the nuclei were always higher than
      the others. However, imperfections may exist: inhomogeneities of pixel
      intensities in a nucleus may cause to define spurious boundaries whereas
      insufficient pixel intensity differences at the border of overlapping nuclei may
      cause to miss some true boundary pixels. In contrast, these imperfections are
      typically observed at the pixel-level, causing local changes in pixel values
      without changing the semantics on a large scale. In response to these issues,
      this article introduces a new nucleus segmentation method that relies on using
      gradient information not at the pixel level but at the object level. To this end,
      it proposes to decompose an image into smaller homogeneous subregions, define
      edge-objects at four different orientations to encode the gradient information at
      the object level, and devise a merging algorithm, in which the edge-objects vote
      for subregion pairs along their orientations and the pairs are iteratively merged
      if they get sufficient votes from multiple orientations. Our experiments on
      fluorescence microscopy images reveal that this high-level representation and the
      design of a merging algorithm using edge-objects (gradients at the object level)
      improve the segmentation results.

PMID- 30211976
TI  - How to Make Railroad Crossings Safer and Smarter: Smart crossing systems are
      adopting the latest in CCTV surveillance and image processing technology to
      visually inspect boom gate conditions, identify trapped objects, and monitor
      objects' movements in real time.

PMID- 30211978
TI  - NADH Autofluorescence-A Marker on its Way to Boost Bioenergetic Research.
AB  - More than 60 years ago, the idea was introduced that NADH autofluorescence could
      be used as a marker of cellular redox state and indirectly also of cellular
      energy metabolism. Fluorescence lifetime imaging microscopy of NADH
      autofluorescence offers a marker-free readout of the mitochondrial function of
      cells in their natural microenvironment and allows different pools of NADH to be
      distinguished within a cell. Despite its many advantages in terms of spatial
      resolution and in vivo applicability, this technique still requires improvement
      in order to be fully useful in bioenergetics research. In the present review, we
      give a summary of technical and biological challenges that have so far limited
      the spread of this powerful technology. To help overcome these challenges, we
      provide a comprehensible overview of biological applications of NADH imaging,
      along with a detailed summary of valid imaging approaches that may be used to
      tackle many biological questions. This review is meant to provide all scientists
      interested in bioenergetics with support on how to embed successfully NADH
      imaging in their research.

PMID- 30211977
TI  - Microfluidic Based Optical Microscopes on Chip.
AB  - Last decade's advancements in optofluidics allowed obtaining an ever increasing
      integration of different functionalities in lab on chip devices to culture,
      analyze, and manipulate single cells and entire biological specimens. Despite the
      importance of optical imaging for biological sample monitoring in microfluidics,
      imaging is traditionally achieved by placing microfluidics channels in standard
      bench-top optical microscopes. Recently, the development of either integrated
      optical elements or lensless imaging methods allowed optical imaging techniques
      to be implemented in lab on chip systems, thus increasing their automation,
      compactness, and portability. In this review, we discuss known solutions to
      implement microscopes on chip that exploit different optical methods such as
      bright-field, phase contrast, holographic, and fluorescence microscopy.

PMID- 30211979
TI  - VTX-1 Liquid Biopsy System for Fully-Automated and Label-Free Isolation of
      Circulating Tumor Cells with Automated Enumeration by BioView Platform.
AB  - Clinicians continue to rely on invasive tissue biopsies as a mean to assess a
      patient's disease and prescribe appropriate treatment regimens. Biopsies not only
      are risky and expensive but also limit the understanding of disease. Circulating
      tumor cells (CTCs) can be isolated from a simple blood draw and offer a promising
      potential to both diagnose and monitor cancer progression. The VTX-1 Liquid
      Biopsy System automates the isolation of clinically relevant CTC populations,
      while simplifying their collection for easy analysis, ultimately expanding the
      clinical possibilities for CTCs. We present here the key features and performance
      of this automated system for isolating CTCs directly from whole blood, both with
      cell spiking experiments and patient samples. As a first step toward the
      characterization of CTCs for research applications and transfer to clinical
      practice, we present workflows for both molecular analyses and automated cell
      enumeration and biomarker quantification with the BioView imaging platform.

PMID- 30211980
TI  - Determination of pesticides residues in vegetable and fruit samples by solid
      phase microextraction with a covalent organic framework as the fiber coating
      coupled with gas chromatography and electron capture detection.
AB  - In this study, a covalent organic framework designated as TpPaNO2 was synthesized
      by a mechanochemical grinding method and then coated on stainless steel wire by a
      sol-gel technique to prepare a solid-phase microextraction fiber. The TpPaNO2
      fiber based solid-phase microextraction coupled with gas chromatography-electron
      capture detection was applied to determine the residues of 11 pesticides
      (trlfuralln, dicofol, alpha-endosulfan, 1-chloro-4-[2,2-dichloro-1-(4
      chlorophenyl)ethenyl]benzene, nitrofen, beta-endosulfan, 1-chloro-4-[2,2-dichloro
      1-(4-chlorophenyl)ethyl]benzene, 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane,
      bifenthrin, permethrin and fenvalerate) in vegetable and fruit samples. The
      effects of extraction time, extraction temperature, sample pH, stirring rate and
      desorption temperature on the extraction efficiency were investigated. Under the
      optimized conditions, the limits of detection for the eleven pesticides were in
      the range of 0.04-0.25 MUg/kg. The recoveries of the eleven pesticides in the
      vegetable and fruit samples were 81.5-111% with the relative standard deviations
      less than 11.2%.

PMID- 30211982
TI  - The FDA nozzle benchmark: "In theory there is no difference between theory and
      practice, but in practice there is".
AB  - The utility of flow simulations relies on the robustness of computational fluid
      dynamics (CFD) solvers and reproducibility of results. The aim of this study was
      to validate the Oasis CFD solver against in vitro experimental measurements of
      jet breakdown location from the FDA nozzle benchmark at Reynolds number 3500,
      which is in the particularly challenging transitional regime. Simulations were
      performed on meshes consisting of 5, 10, 17, and 28 million (M) tetrahedra, with
      Deltat  =  10-5 seconds. The 5M and 10M simulation jets broke down in reasonable
      agreement with the experiments. However, the 17M and 28M simulation jets broke
      down further downstream. But which of our simulations are "correct"? From a
      theoretical point of view, they are all wrong because the jet should not break
      down in the absence of disturbances. The geometry is axisymmetric with no
      geometrical features that can generate angular velocities. A stable flow was
      supported by linear stability analysis. From a physical point of view, a finite
      amount of "noise" will always be present in experiments, which lowers transition
      point. To replicate noise numerically, we prescribed minor random angular
      velocities (approximately 0.31%), much smaller than the reported flow asymmetry
      (approximately 3%) and model accuracy (approximately 1%), at the inlet of the 17M
      simulation, which shifted the jet breakdown location closer to the measurements.
      Hence, the high-resolution simulations and "noise" experiment can potentially
      explain discrepancies in transition between sometimes "sterile" CFD and
      inherently noisy "ground truth" experiments. Thus, we have shown that numerical
      simulations can agree with experiments, but for the wrong reasons.

PMID- 30211981
TI  - Long-Term Engraftment (16 Years) of Myoblasts in a Human Infarcted Heart.
AB  - We report the case of a patient who had undergone injections of myoblasts in an
      infarct area 16 years before being referred for heart transplantation. The
      pathological examination of the explanted heart found persisting myotubes
      embedded in fibrosis. This finding supports the ability of myoblasts to survive
      in harsh environments, which can make them appealing candidates for
      transplantation in diseases requiring supply of new myogenic cells. Stem Cells
      Translational Medicine 2018;7:705-708.

PMID- 30211983
TI  - Taurine: A Regulator of Cellular Redox Homeostasis and Skeletal Muscle Function.
AB  - Taurine is a nonproteinogenic beta-aminosulfonic acid. Important dietary sources
      of taurine are fish and seafood. Taurine interacts with ion channels, stabilizes
      membranes, and regulates the cell volume. These actions confirm its high
      concentrations in excitable tissues like retina, neurons, and muscles. Retinal
      degeneration, cardiomyopathy, as well as skeletal muscle malfunction are evident
      in taurine-deficient phenotypes. There is evidence that taurine counteracts lipid
      peroxidation and increases cellular antioxidant defense in response to
      inflammation. In activated neutrophils, taurine reacts with hypochloric acid to
      form taurine chloramine, which triggers the Kelch-like ECH-associated protein 1
      nuclear factor E2-related factor 1 (Keap1-Nrf2) pathway. Consequently, Nrf2
      target genes, such as heme oxygenase-1 and catalase, are induced. Furthermore,
      taurine may prevent an overload of reactive oxygen species (ROS) directly by an
      inhibition of ROS generation within the respiratory chain. Taurine affects
      mitochondrial bioenergetics and taurine-deficient mice exhibit an impaired
      exercise performance. Moreover, some studies demonstrate that taurine enhances
      the glycogen repletion in the postexercise recovery phase. In the case of taurine
      deficiency, many studies observed a phenotype known in muscle senescence and
      skeletal muscle disorders. Overall, taurine plays an important role in cellular
      redox homeostasis and skeletal muscle function.

PMID- 30211984
TI  - Development of Mixed-Anion Photocatalysts with Wide Visible-Light Absorption
      Bands for Solar Water Splitting.
AB  - Rapid fossil-fuel consumption, severe environmental concerns, and growing energy
      demands call for the exploitation of environmentally friendly, recyclable, new
      energy sources. Fuel-producing artificial systems that directly convert solar
      energy into fuels by mimicking natural photosynthesis are expected to achieve
      this goal. Among them, the conversion of solar energy into hydrogen energy
      through the photocatalytic water-splitting process over a particulate
      semiconductor is one of the most promising routes due to advantages such as
      simplicity, cheapness, and ease of large-scale production. Abundant metal oxide
      photocatalysts have been developed in the last century, but most are only active
      under UV-light irradiation. To harvest a much wider range of the solar spectrum,
      the development of photocatalysts with wide visible-light absorption bands has
      become increasingly popular this century. Herein, a brief overview of materials
      developed for promising solar water splitting, with an emphasis on a mixed-anion
      structure and wide visible-light absorption bands, is presented, with some basic
      information on the principles, approaches, and research progress on the
      photocatalytic water-splitting reaction with particulate semiconductors. Typical
      progress on research into one- and two-step (Z-scheme) overall water-splitting
      systems by utilizing mixed-anion photocatalysts is highlighted, together with
      research strategies and modification methods.

PMID- 30211985
TI  - What Does a Modern Anatomist Look like? Current Trends in the Training of Anatomy
      Educators.
AB  - Anatomical sciences are foundational to the health professions, yet little is
      known about the qualifications of anatomy educators at the graduate and
      professional level in the United States. Moreover, there is concern that the
      number of qualified anatomy educators being trained may be insufficient to meet
      the growing demand posed by new and expanded programs in medicine and allied
      health specialties. The authors surveyed anatomists from across the country to
      (i) characterize the educational credentials of current anatomy educators and
      (ii) assess the perceived need for education-focused postdoctoral positions or
      formal mentorships to prepare anatomists for teaching-intensive faculty
      positions. To probe the survey responses more deeply, one-on-one interviews were
      conducted with eight individuals selected to represent a diverse sample of
      respondents in terms of institution, gender, and academic rank. Results indicate
      that 30-40% of educators at the graduate level and approximately 60% of those at
      the undergraduate level lack graduate coursework in histology, embryology, and
      neuroanatomy. Forty-five percent of respondents had completed a postdoctoral
      fellowship. Eighty-six percent replied "yes/maybe" to the question of whether an
      anatomy education postdoctoral fellowship would benefit doctoral graduates. The
      top 3 reasons for this recommendation were to (i) establish independent
      educational research, (ii) improve a publication record, and (iii) gain
      additional teaching experience. Notable weaknesses of education-focused
      postdoctoral training were related to finances, fear of exploitation, and
      undervaluing of teaching. Moving forward, postdoctoral fellowships and other
      forms of postgraduate training may represent a key strategy for training
      anatomists in the current educational climate. Anat Sci Educ 00: 000-000. (c)
      2018 American Association of Anatomists.

PMID- 30211986
TI  - Selective and sensitive determination of tetracyclines by HPLC with
      chemiluminescence detection based on a cerium(IV)-methoxylated cypridina
      luciferin analogue system.
AB  - A novel approach for the simultaneous and selective analysis of
      chlortetracycline, doxycycline, 4-epichlortetracycline, oxytetracycline,
      metacycline, and tetracycline by high-performance liquid chromatography coupled
      with sensitive post-column chemiluminescence reaction was set up. Six
      tetracyclines were separated through a simple and effective isocratic procedure
      using a mixture of acetonitrile and 3.5 mM methanesulfonic acid. After that,
      intensive chemiluminescence signals were produced by the reaction between
      cerium(IV) and methoxylated cypridina luciferin analogues system in the presence
      of tetracyclines. Under the appropriate experimental conditions, the developed
      method was evaluated by testing of linearity, limits of detection, precision, and
      accuracy. The limit of detection was from 2 to 10 nM and relative standard
      deviation of intraday precision was below 9%. The developed high-performance
      liquid chromatography with chemiluminescence method has been performed for the
      with trace analysis of tetracycline antibiotic residues in milk samples with
      satisfactory results.

PMID- 30211988
TI  - 6th Strasbourg Summer School in Chemoinformatics.

PMID- 30211987
TI  - Postnatal Administration of Lactobacillus rhamnosus HN001 Ameliorates Perinatal
      Broad-Spectrum Antibiotic-Induced Reduction in Myelopoiesis and T Cell Activation
      in Mouse Pups.
AB  - SCOPE: This study addresses whether administration of Lactobacillus rhamnosus
      HN001 could mitigate the effects of a compromised gut microbiota on the
      composition of mature leukocytes and granulocyte-macrophage progenitor cells
      (GMPs) in newborn mice. METHODS AND RESULTS: Pregnant dams receive oral broad
      spectrum antibiotics, which dramatically decrease the gut microbial composition
      analyzed by 16S rRNA sequencing. Perinatal antibiotic treatment decreases the
      proportions of bone marrow (BM) GMPs (postnatal day (PND2): 0.5% vs 0.8%, PND4:
      0.2% to 0.6%) and mature granulocytes (33% vs 24% at PND2), and spleen
      granulocytes (7% vs 17% at PND2) and B cells (PND2:18% vs 28%, PND4:11% vs 22%).
      At PND35, T helper (Th) cells (20% vs 14%) and cytotoxic T (Tc) cells (10% vs 8%)
      decrease in the spleen. Oral administration of L. rhamnosus HN001 to neonatal
      pups (PND1-7) restores the antibiotic-induced changes of GMPs and granulocytes in
      BM and spleen, and further increases splenic granulocytes in control pups. At
      PND35, splenic proportions of B and Th but not Tc cells are restored. CONCLUSION:
      Postnatal administration of a single bacterial strain efficiently restores
      granulopoiesis and most T cell activation in neonatal mice that suffer from a
      perinatal antibiotic-induced compromised gut microbiota at birth.

PMID- 30211989
TI  - Dental Plaque Removal and Re-Accumulation: A Clinical Randomized Pilot Study
      Evaluating a Gel Dentifrice Containing 2.6% Edathamil.
AB  - OBJECTIVES: To evaluate and compare examiner-assessed changes in enamel gloss,
      extrinsic dental stain, and surface smoothness following one, two, four, and
      eight weeks of twice-daily use of an experimental low abrasivity desensitizing
      dentifrice (relative dentin abrasivity [RDA] ~40) containing 5% sodium
      tripolyphosphate (STP) chemical cleaning agent and 1% aluminum trioxide abrasive.
      This was compared with an ultra-low abrasivity dentifrice (5% STP only; RDA ~13),
      a moderate abrasivity fluoride dentifrice (RDA ~80), and a higher abrasivity
      marketed whitening dentifrice (RDA ~142). METHODS: This was a single-center,
      examiner-blind, randomized, controlled, parallel group study in healthy adults
      stratified by gloss score and age. Following a washout period with a conventional
      silica abrasive dentifrice, subjects received a dental scale and polish and were
      randomized to treatment. Subjects brushed their teeth for two minutes, twice
      daily, with their assigned dentifrice. Enamel gloss was assessed visually by
      comparing the facial surfaces of the maxillary incisors to the Sturzenberger
      gloss standards. Extrinsic dental stain was measured on the 12 anterior teeth
      (facial and lingual) using the Macpherson modification of the Lobene Stain Index
      (MLSI). Tooth smoothness was assessed using scanning electron microscope (SEM)
      analysis of a silicone impression of the central incisors. RESULTS: Of 120
      screened subjects, 95 were randomized to the study. Subjects using the low
      abrasivity aluminum trioxide/STP dentifrice demonstrated statistically
      significant (p < 0.05) and increasing improvements in surface gloss over baseline
      at all time points, with a significant treatment effect compared to all other
      study dentifrices from Week 2 (p < 0.05). With respect to dental stain, the low
      abrasivity dentifrice group had the lowest stain score at each post-treatment
      time point and demonstrated statistically significantly less stain compared to
      all study dentifrices at Weeks 2 (p < 0.05) and 8 (p < 0.01). For tooth
      smoothness, at Week 8, statistically significant increases in surface smoothness
      were observed for most treatment groups compared to baseline (p < 0.05), except
      for the moderate abrasivity dentifrice. CONCLUSIONS: This study shows the benefit
      of a low abrasivity dentifrice containing STP and aluminum trioxide in reducing
      stain build-up and increasing tooth gloss compared to a non-alumina ultra-low
      abrasivity STP-containing dentifrice, and moderate and high abrasivity
      dentifrices, over an eight-week period.

PMID- 30211990
TI  - Gingivitis Models - Relevant Approaches to Assess Oral Hygiene Products.
AB  - OBJECTIVES: To review the application of gingivitis prevention and treatment
      models to assess the efficacy of mechanical and chemotherapeutic oral hygiene
      interventions following shorter- and longer-term use. METHODS: Representative
      published clinical trials evaluating the shorter- and longer-term anti-gingivitis
      efficacy of stannous fluoride dentifrice, cetylpyridinium chloride (CPC) rinse,
      and oscillating-rotating (O-R) electric rechargeable toothbrushes were reviewed.
      Key gingivitis indices, including the Loe-Silness Gingival Index (LS), Lobene
      Modified Gingival Index (MGI), Gingival Bleeding Index (GBI), Papillary Bleeding
      Index (PIBI), and the Mazza modification of the PIBI (Mazza GI), were evaluated
      for their relative validity and sensitivity in evaluating prevention and
      treatment outcomes. RESULTS: Twenty clinical trials were evaluated, including 11
      treatment studies and 9 prevention trials. Collectively, the findings
      demonstrated the efficacy of stabilized stannous fluoride toothpaste, CPC rinses,
      and O-R electric toothbrushes in improving gingival health both in longer-term
      prevention and shorter-term treatment models. The studies employed various
      frequently used gingivitis indices. The indices were sufficiently sensitive to
      elucidate treatment differences. CONCLUSIONS: Based on the results of this
      review, gingivitis prevention and treatment studies are valid approaches to show
      treatment effects, and their utilization is dependent upon whether the intention
      is to evaluate "reducing the onset of gingivitis" or "reducing the severity of
      existing gingivitis." Various indices, including the LS, MGI, GBI, PIBI, and
      Mazza GI indices, provide valid measurements for evaluating gingivitis in
      treatment and prevention models. Shorter-term treatment models allow for
      efficient efficacy evaluation in clinically relevant populations with existing
      disease.

PMID- 30211991
TI  - The Efficacy of Aged Garlic Extract on Gingivitis - A Randomized Clinical Trial.
AB  - OBJECTIVES: To assess gingivitis and gingival bleeding following the consumption
      of Aged Garlic Extract versus placebo for a period of four months. METHODS: A
      randomized, controlled, examiner-blind, two-treatment parallel group study was
      conducted. Participants were stratified and randomly assigned equally to a
      regimen group using Aged Garlic Extract (AGE) or a control group, based on
      gender, age, baseline number of bleeding sites, and gingival health status.
      Assessment was performed at baseline and at one, two, three, and four months.
      Clinical assessment was conducted by three experienced calibrated examiners.
      RESULTS: One hundred and fifty-one participants followed the inclusion criteria;
      50.3% males, with an average age of 32.7 +/- 8.2 years. Only 134 subjects
      completed the four-month study (11.3% attrition rate). A statistically
      significant decrease of the Modified Gingival Index and Gingival Bleeding Index
      scores was shown for the AGE compared to the placebo group, both between and
      within groups (p < 0.001). CONCLUSIONS: This research demonstrated that daily
      consumption of AGE benefits oral health by reducing gingival inflammation and
      gingival bleeding, as compared to a placebo control.

PMID- 30211992
TI  - Hydroxyapatite and Self-Assembling Peptide Matrix for Non-Oxidizing Tooth
      Whitening.
AB  - OBJECTIVES: The aim of this combined in vitro and in vivo study was to evaluate
      the efficacy of tooth whitening using a mixture of Self- Assembling Peptide
      Matrix (SAPM) and hydroxyapatite (HA). METHODS: The mixture was applied on
      stained bovine teeth, and the tooth color was measured using a spectrophotometer;
      mean changes in L*a*b values between measurements were expressed as DE.
      Additionally, the nature of the surface layer was investigated by ATRFTIR and
      EDX. The optical changes due to the additional surface layer were measured using
      a goniometer. Finally, a proof-of-concept clinical study was performed
      investigating the mixture of SAPM+HA. RESULTS: The results verified that the SAPM
      remained on the tooth surface and acted as a temporary adhesive to attach the HA
      particles to the tooth surface. Further, the optical changes due to the
      additional surface layer indicated a diffuse reflection to be the origin of the
      optical whitening. Lastly, the mixture of SAPM+HA showed significant and visible
      whitening after one application, increasing throughout the first week of home
      application (DE = 4.9 +/- 3.3) and remaining stable for 30 days (DE = 4.8 +/-
      3.6). CONCLUSIONS: The combination of SAPM+HA particles caused optical whitening
      based on diffuse reflection by the HA particles on the tooth surface. The
      whitening effect and its magnitude observed in vitro were also seen in vivo.

PMID- 30211993
TI  - A Randomized Controlled Clinical Trial to Evaluate the Efficacy of an Oscillating
      Rotating Electric Toothbrush, a Stannous Fluoride Dentifrice, and Floss on
      Gingivitis.
AB  - OBJECTIVES: To evaluate the gingival health efficacy of an oscillating-rotating
      electric toothbrush, a stannous fluoride dentifrice, and dental floss in adults
      with mild-to-moderate gingivitis. METHODS: This was a single-center, randomized,
      controlled, examiner-blind, two-treatment, eight-week parallel group study in
      adults with at least 20 gingival bleeding sites. Eligible subjects were
      randomized equally to one of two groups: experimental oral hygiene group that
      included an Oral-B(r) oscillating-rotating electric toothbrush with round brush
      head (D20/EB20), Crest(r) stabilized stannous fluoride dentifrice (SnF2 1100 ppm
      F, NaF 350 ppm F), and Oral-B(r) Glide(r) floss; or regular oral hygiene control
      group that included a regular manual toothbrush (Oral-B(r) Indicator 35) and
      Crest(r) anti-cavity sodium fluoride dentifrice (NaF 1450 ppm F). Subjects
      followed manufacturer's instructions and used their assigned products over an
      eight-week period. Gingival health was measured at baseline, Week 4, and Week 8
      using three assessments: Gingival Bleeding Index (GBI), number of bleeding sites,
      and Modified Gingival Index (MGI). Analysis of Covariance was used to compare
      gingival health between treatment groups. RESULTS: One hundred and twenty
      subjects, mean age 44 years (range: 21 to 74 years), were assessed at baseline
      (60 per group); 113 subjects (57 in control group, 56 in experimental group)
      completed the study with fully evaluable data. At baseline, the groups were
      balanced; overall means were 0.41 for GBI, 51.7 for bleeding sites, and 1.44 for
      MGI. Only the experimental group showed statistically significant reductions from
      baseline (p < 0.0001) for all three gingivitis assessments at both Weeks 4 and 8.
      At these time points, better gingival health for the experimental group was seen
      as significantly lower adjusted mean scores versus the control group (p < 0.0001)
      for all three assessments. Reductions in favor of the experimental group at Weeks
      4 and 8, respectively, were 51% and 45% for GBI, 46% and 40% for number of
      bleeding sites, and 37% and 20% for MGI. The study treatments were well
      tolerated. CONCLUSIONS: Over an eight-week period, an oral hygiene routine with
      an oscillating-rotating electric toothbrush, stannous fluoride dentifrice, and
      floss significantly improved gingivitis compared to regular hygiene with a manual
      toothbrush and an anti-cavity sodium fluoride dentifrice.

PMID- 30211994
TI  - [Bell's palsy: different doctor, different care?]
AB  - OBJECTIVE: To compare the diagnostic work-up and treatment strategy of Bell's
      palsy by: general practitioners (GPs); ear, nose and throat (ENT) specialists;
      and neurologists in the Netherlands. DESIGN: Cross-sectional survey. METHOD: GPs,
      ENT specialists and neurologists were asked to participate in an online survey on
      the diagnosis and treatment of Bell's palsy. Results per specialty were analysed
      using descriptive statistics and chi-squared test. RESULTS: A total of 415
      clinicians participated, including 149 GPs, 123 ENT specialists, and 143
      neurologists. The answers from the three disciplines showed significant
      differences concerning history taking, physical examination, alarm symptoms,
      treatment strategy and follow-up. ENT specialists more frequently asked about
      hearing loss (90%), whereas neurologists enquired about weakness in arms and legs
      (62%). GPs less often ask about tick bites than clinicians in ENT and neurology,
      respectively (36% vs. 89% and 71%). Neurologists rarely performed otoscopy (21%),
      but more frequently tested eye movements (78%) than GPs (33%) and ENT specialists
      (20%). Compared to GPs and neurologist, ENT specialists more frequently reported
      the supplementation of Prednisone treatment with antiviral agents (45% vs. 9% and
      6 % resp.). Furthermore, the time interval to the follow-up visit varied strongly
      between clinicians, ranging between a few days to six weeks after the first
      clinic visit. CONCLUSION: This study shows that the diagnostic work-up and
      treatment strategy for Bell's palsy in the Netherlands is highly dependent on the
      clinician's specialty. Despite the fact that equivalent guidelines are in place,
      GPs, ENT specialists and neurologists gave different answers to questions
      concerning diagnostics and treatment. This finding suggests that more attention
      should be paid to the implementation of and adherence to the multidisciplinary
      guideline for Bell's palsy.

PMID- 30211995
TI  - [CV-building for medical students].
AB  - Today's medical students invest large amounts of time and energy into building
      what is believed to be the ideal resume to ensure admission to residency
      programmes. In this clinical lesson, we present three Dutch pre-graduate medical
      students who approach CV-building and the perceived pressure to be a typical
      overachiever on paper in different manners. In addition, we conducted a survey
      among the heads of 160 Dutch residency programmes. Based on this, we discuss
      whether what is generally believed among students to be necessary for admission
      to residency programmes is in agreement with what heads of Dutch residency
      programmes report their selection of successful candidates to be based on. The
      influences of millennials' world view and today's medical culture are included in
      the discussion, leading us to the conclusion that a substantial mental and
      cultural shift is necessary on multiple levels to significantly change the way in
      which medical students approach CV-building.

PMID- 30211996
TI  - [Student-driven education; catalyst of change in medical curriculum].
AB  - Changing healthcare requires future physicians to have some basic knowledge of
      fields related to medicine. There is also a growing need for multidisciplinary
      and interdisciplinary education in the basic medical curriculum. The basic
      curriculum is currently being revised on the national level, but this is taking a
      long time. We are using a practical example to discuss how student-driven
      education could be a catalyst for rapid change in medical education.

PMID- 30211998
TI  - [10 tips for medical student supervision during clinical placements].
AB  - Good supervision during clinical placements is essential for the medical
      student's learning process. Supervision of medical students can, however, be
      challenging for doctors and resident physicians, and it can also be challenging
      for students to request this supervision. Here we give 5 tips for provision of
      good supervision and 5 tips for requesting good supervision, on the basis of
      three relevant educational theories - 'self-regulated learning', 'cognitive
      apprenticeship', and 'communities of practice'.

PMID- 30211997
TI  - [Second opinion abroad; motives and experiences of patients with incurable
      cancer].
AB  - OBJECTIVE: To explore motives and experiences of patients with incurable cancer
      who are looking across the border for second opinions or treatments or are
      considering to do so. DESIGN: Qualitative, semi-structured interview study.
      METHOD: A total of 24 patients with incurable cancer from two Dutch hospitals
      were interviewed by phone. All interviews were coded independently by two
      researchers and then analysed inductively, without any pre-specified theoretical
      framework. RESULTS: Patients were looking for second opinions or treatments
      because they found it very difficult to accept a sudden diagnosis of incurable
      disease. They experienced little guidance during this transition. Patients felt
      they were not offered any treatment options because of imperative protocols. Many
      patients were in great need of some form of hope. There were often high
      expectations - unrealistic or not - of the possibilities abroad. Oncologists'
      reactions to patients' choices were very diverse. While disapproving reactions
      were unable to influence patients' choices, well-substantiated arguments were
      sometimes successful in influencing patients' choices. CONCLUSION: More guidance
      seems advisable for some patients to help them deal with a diagnosis of incurable
      disease. Dutch oncologists might be able to offer alternative forms of hope to
      these patients, who have a great need for this. If physicians speak with patients
      about what a treatment abroad may or may not be able to provide, this might
      benefit patients.

PMID- 30211999
TI  - [Students of medicine are turning medical education on its head; from a closed to
      an open learning environment].
AB  - These days, students are gathering their own source materials using Google and
      leave the required textbooks on the shelves. This means the future of medical
      education lies in facilitating and freely sharing modern learning resources. This
      rapid shift, away from traditional textbooks, is causing unrest in academic
      education. The faculty is losing control and the overall picture. Existing
      teaching materials with strict copyrights have made it difficult for teachers and
      students to learn from each other. The productivity and professional curiosity of
      a sector that not only desires but also requires life-long learning, is being
      undermined by meaningless barriers and duplication of work. Free learning
      resources are making it easier for both students and professionals to learn,
      share and quickly get access to the right information. In this article, we
      explain what this means for medical education, what is needed and we provide a
      few examples.

PMID- 30212000
TI  - [Ocular syphilis: a warning sign of an HIV infection].
AB  - A 29-year-old male presented at the ER with a red and painful left eye with
      sudden and progressive loss of vision within a week. His visual acuity was 1/60.
      Slit lamp investigation showed inflammatory cells throughout the anterior chamber
      and vitreous body, and a hyperaemic and swollen optic disc with retinal lesions,
      indicating a panuveitis combined with multifocal chorioretinitis. Due to the
      progressive nature, an infectious cause was suspected: positive syphilis serology
      and HIV serology confirmed this. The diagnosis of ocular syphilis was a first
      manifestation of a syphilis infection. Moreover, this was a warning sign for an
      associated HIV infection. Approximately 40% of all syphilis cases in the
      Netherlands are co-infected with HIV. Due to the high co-infection rate, HIV
      should always be considered when diagnosing ocular syphilis. The ocular syphilis
      was treated as a neurosyphilis with 18 million units of penicillin per day, and
      the patient's vision eventually returned to 0.4.

PMID- 30212001
TI  - [Vitamin B6 deficiency caused by the use of levodopa].
AB  - BACKGROUND: There are indications that the use of levodopa/carbidopa can cause
      symptomatic vitamin B6 deficiency. However, this has only been described for
      patients who used the product in the form of an intestinal gel. CASE DESCRIPTION:
      We are describing 3 patients who developed vitamin B6 deficiency while using
      levodopa/carbidopa in tablet form. All 3 patients developed symptoms consistent
      with peripheral axonal polyneuropathy. CONCLUSION: The cases of our patients are
      providing support for the idea that oral use of levodopa/carbidopa can cause
      symptomatic vitamin B6 deficiency.

PMID- 30212002
TI  - [Infections during glucocorticoid use].
AB  - Glucocorticoid treatment increases the risk of opportunistic infection.
      Infections that can arise during glucocorticoid use, and for which preventative
      measures can be taken, include reactivation of latent tuberculosis and hepatitis
      B, pneumococcal and Pneumocystis jiroveci pneumonia, influenza, herpes zoster and
      Strongyloides stercoralis hyperinfection syndrome. The risk of such infections
      depends upon the duration of glucocorticoid use and dosage, as well as
      comorbidity and comedication. It is important to enquire about vaccinations,
      travel, exposure and previous infections when taking a case history. Possible
      infectious complications should be considered in patients who are receiving high
      dose glucocorticoids treatment amounting to more than 420 mg PED per 4 weeks.
      Preventative measures are not usually required in patients who receive a short
      high-dosed treatment (30 mg PED in 7 days) or prednisolone at a dosage of < 15
      mg/day.

PMID- 30212003
TI  - [Latent tuberculosis infection after an internship in India].
AB  - BACKGROUND: On returning from a period in a country where tuberculosis is
      endemic, e.g. a medical internship abroad, screening for tuberculosis takes
      place. The tuberculin skin test (Mantoux test) and the interferon-gamma release
      assay test are available for this purpose. CASE DESCRIPTION: We describe a 23
      year-old female medical intern who was treated preventively with a
      tuberculostatic drug due to a latent tuberculosis infection (LTBI) following an
      internship in India. This treatment was prematurely discontinued due to increased
      transaminases (ALT, AST) and physical side effects that impacted negatively on
      her general wellbeing and on her ability to function during her later
      internships. CONCLUSION: Long-term preventive treatment for a health care
      professional with an LTBI is often indicated. However, this treatment can have
      negative side effects.

PMID- 30212004
TI  - [Physician, disclose thyself! Self-disclosure as an educational tool].
AB  - Supervisor self-disclosure is essential for both personal and professional
      development of the next generation of doctors. We highlight the importance of
      self-disclosure and urge doctors in a supervising role to embed self-disclosure
      in their supervisory activities. Effective supervision of residents and interns
      encompasses many elements. Self-disclosure positively contributes to a safe
      teaching environment as well as a nurturing supervisor-trainee relationship. Self
      disclosure can be used in many supervisory settings to benefit the development of
      residents and interns. It is of the utmost importance that self-disclosure should
      be used consciously and at suitable moments. Tools to achieve optimal self
      disclosure are provided.

PMID- 30212005
TI  - [Infectious disease control for asylum seekers entering the Netherlands in 2018:
      is reform necessary?]
AB  - The number of asylum seekers entering the Netherlands has increased. However, the
      screening, detection and treatment of infectious diseases in asylum seekers has
      barely changed over the last 15 years. Infectious diseases, including vaccine
      preventable diseases are being carried into the Netherlands by asylum seekers.
      However, neither the number nor the type of disease pose a real threat to public
      health. It is important to be alert to carriers of multidrug-resistant organisms
      among asylum seekers. National screening programmes are offered for a number of
      infectious diseases, but not for all diseases relevant to asylum seekers. Hygiene
      and sanitary facilities are essential in the care of asylum seekers, due mainly
      to the relatively high prevalence of scabies. Infectious disease control for
      asylum seekers in the Netherlands can be improved. Focusing on the country of
      origin is important. The current European Centre for Disease Prevention and
      Control Guidelines concerning medical care for asylum seekers should be
      implemented in the Netherlands.

PMID- 30212006
TI  - [A boy with a twisted knee].
AB  - A 14-year-old boy presented with a painful knee following a distorsion. He was
      unable to actively extend his lower leg. Conventional radiography showed no signs
      of a fracture. Both ultrasound imaging and MRI, however, demonstrated
      haemarthrosis and an osteochondral defect of the lateral femoral condyle.
      Apparently, an osteochondral lesion had developed due to patellar luxation. The
      osteochondral fragment was fixated using absorbable compression screws.

PMID- 30212007
TI  - [The Student t-test is a beer test].
AB  - The Student-t-test, one of the most used statistical tests in medicine, was
      developed by a beer brewer. From around 1900, the Irish Guinness brewery started
      recruiting scientists for the position of brewer in order to apply science to the
      production of beer in large quantities while maintaining consistency in terms of
      quality. One of these brewers was mathematician and chemist William Sealy Gosset
      (1876-1937). He developed statistical methods to deal with small sample surveys.
      Gosset's methods, and the accompanying t-distribution tables, enabled Guinness to
      take intelligent decisions about which ingredients to use, allowing them to
      produce high-quality beer that consistently tasted the same. Gosset wanted to
      publish his findings in scientific journals; however, the Guinness brewery was
      unwilling, as this could jeopardise their advantage over other breweries. They
      came to a compromise, in which Guinness allowed Gosset to publish his findings,
      as long as he used a pseudonym: Student. The Student's t-distribution remains one
      of the cornerstones of modern statistics.

PMID- 30212009
TI  - [Pneumocystis prophylaxis during glucocorticoid use?]
AB  - Pneumocystis jiroveci pneumonia (PJP) is a much-feared complication of the use of
      immunosuppressive drugs. There is no current consensus on the indications for PJP
      prophylaxis in patients with rheumatological diseases who are receiving higher
      dose glucocorticoid treatment over a prolonged period. The decision on whether or
      not to administer prophylaxis depends primarily on the Number Needed to Treat
      (NNT) vs the Number Needed to Harm (NNH) of trimethoprim/sulfamethoxazole
      (TMP/SMX) or other forms of prophylaxis. A recent retrospective study from South
      Korea supports the efficacy and safety of TMP/SMX for patients using >= 30 mg
      prednisone for > 1 month, especially in those with high-risk disease or other
      risk factors. Surveillance of regional and national PJP incidence, along with
      possible predictors, may help in gaining a better understanding of risk groups
      and in drawing up a regional, or preferably national, protocol.

PMID- 30212008
TI  - [A man with thoracic pain after visiting the tropics].
AB  - A 25-year-old man presented to the Emergency Department with thoracic pain and
      coughing after travelling through South America. Radiologic work-up revealed
      diffuse multifocal consolidations surrounded by a ground-glass halo and thoracic
      lymphadenopathy. A urine antigen test was positive for Histoplasma capsulatum, a
      fungus that is endemic in South America and which causes a severe pulmonary
      infection in 5% of the infected patients.

PMID- 30212010
TI  - [Studying abroad; the other side of the coin].
AB  - All Dutch universities encourage their medical students to follow part of their
      Bachelor's or Master's degree abroad. In doing so, students encounter other
      cultures and see medicine from a global perspective, including possible
      inequalities in health care access. Though it is well-known that these
      experiences often have a profound impact on an individual student, little is
      known as to whether this also leads to better future physicians. More
      importantly, travelling to certain areas where endemic infections occur poses an
      additional risk. Universities should inform students adequately about possible
      health risks, while travelling abroad for their studies. Students should realize
      that in addition to it potentially being a great experience, despite all
      precautions, it could also be a negative experience and there is the possibility
      of contracting a disease.

PMID- 30212011
TI  - [Metal implants and airport security checks].
AB  - Orthopaedic surgeons and trauma surgeons in the Netherlands are implanting 65,000
      joint replacements and treating nearly 300,000 fractures per year. For many
      travellers with a metal implant - but also for the physicians who are treating
      them - it is unclear what the consequences will be when they have to go through
      airport security checks. These checks follow a fixed procedure in accordance with
      European rules which involves travellers passing through a number of visible and
      invisible barriers. The first barrier is usually a metal detector or a millimetre
      wave scanner; when the implant has been detected, this is followed by a body
      search. The electromagnetic field of a metal detector penetrates into the body;
      the metal detector has therefore a higher detection rate for metal implants than
      a millimetre wave scanner, of which radio waves reach up to or just below the
      skin. Medical documentation can help reassure the traveller or the security
      officer, but possible additional checks cannot be avoided.

PMID- 30212012
TI  - [Valproic acid toxicity due to misinterpretation of plasma levels: increase in
      unbound fraction caused by hypoalbuminaemia and renal dysfunction].
AB  - BACKGROUND: Valproic acid is one of the most widely prescribed drugs for the
      treatment of epilepsy and bipolar disorder. As only the unbound fraction of a
      medicinal product is pharmacologically active, in some strong protein-bound
      psychotropic drugs such as valproic acid and phenytoin, a rise in this fraction
      can lead to severe toxicity. CASE DESCRIPTION: A 65-year-old male with a type 1
      bipolar disorder developed a number of neurological symptoms including
      sluggishness, muscle weakness, difficulty in walking and disorders of micturition
      after his mood stabiliser was changed to valproic acid. Recognition of drug
      toxicity was delayed as his total plasma valproic acid levels were within the
      therapeutic range. Later it became apparent that the patient had toxic unbound
      valproic acid levels due to hypoalbuminaemia and impaired renal function.
      CONCLUSION: Clinicians should always consider drug toxicity in patients who show
      neurological symptoms and use highly protein-bound psychotropic drugs, even if
      the total plasma concentration of the drug is in the therapeutic range.

PMID- 30212013
TI  - [Medical scribe in a trauma surgery outpatient clinic; shorter, cheaper
      consultations and satisfied doctors].
AB  - OBJECTIVE: To measure the effects of a medical scribe in an orthopaedic trauma
      surgery outpatient clinic on consultation time, patient satisfaction, doctor
      satisfaction and costs. DESIGN: Cross-sectional study. METHOD: At a level-1
      trauma centre in the Netherlands, all standard outpatient trauma consultations
      were performed either with or without a medical scribe, for a period of 10 weeks.
      Length of consultation time was defined as the time from commencement of the
      consultation until the moment the electronic health record had been completely
      filled out and checked by the surgeon. Patient satisfaction was assessed using a
      validated questionnaire (PSQ-NL-18). Doctor satisfaction was assessed through a
      non-structured interview when the study ended in which doctors voiced their
      opinion on the cooperation with the medical scribe and the feasibility of
      employing medical scribes. Staffing costs of consultations were calculated by
      multiplying the gross salaries of surgeons and scribes (in ?/min) and the
      consultation time (in minutes). RESULTS: A total of 151 patients were seen with
      the scribe, and 304 without the scribe. The mean consultation time was 3.2
      minutes shorter in the study group compared with the control group (95% CI: 2.2
      4.2). Patient satisfaction did not differ between the groups (mean PSQ-NL-18
      total score: 4.4 (SD: 0.5) in the group with scribe and 4.3 (SD: 0.5) in the
      group without scribe (p = 0.45). The physicians felt they had more patient
      interaction and found working with the medical scribe satisfying. Mean staffing
      costs with the medical scribe (?19.35 per consultation, SD 10.4) were
      significantly lower than without (?21.82 per consultation, SD 11.3; p = 0.03).
      Annually, a cost reduction of ?10,500 could be achieved in this outpatient clinic
      by the introduction of a medical scribe. CONCLUSION: The use of a medical scribe
      for the documentation during a consultation in an outpatient clinic with a high
      patient turnover seems to increase doctor productivity and doctor satisfaction.

PMID- 30212015
TI  - [Antibiotics not indicated for uncomplicated diverticulitis; the argument is
      settled].
AB  - Diverticulitis generally has a good prognosis, and several studies have shown
      that uncomplicated diverticulitis can be successfully treated without
      administration of antibiotics. Questions remained about long-term outcomes, but
      the two-year follow-up results of the DIABOLO study confirm that initial
      management without antibiotics yields favourable short-term and long-term
      outcomes.

PMID- 30212014
TI  - [Air configurations in the pelvis].
AB  - A 74-year-old man presented to the Emergency Department after a fall from a
      ladder. Plain radiographic screening of the lumbar spine revealed an
      unanticipated curvilinear, oval-shaped air configuration in the pelvis. Computed
      tomography of the lumbar spine showed air within the bladder wall and lumen.
      Urine cultures were positive for Escherichia coli. The patient was discharged
      after bladder drainage and empiric antibiotic treatment.

PMID- 30212016
TI  - [Preference for assisted dying: observations and considerations].
AB  - What is preferable for a patient who has requested euthanasia: self
      administration of a lethal drink (assisted dying), or to have a drug administered
      intravenously (euthanasia)? We analysed data from a total of 226 patients who had
      been helped with assisted dying. In 86% of the cases (195 patients) death
      occurred within 30 minutes. Thus, the predictability of the process of dying
      after drinking the lethal drink is relatively high. This implies that other
      aspects can be taken into consideration when making the choice between euthanasia
      and assisted dying, including the patient's own responsibility and the impact the
      method will have on relatives. On the grounds of our analysis and these
      considerations, our preference is for assisted dying, subject to medical contra
      indications. We expect that, with this knowledge, more doctors will be able to
      help with assisted dying.

PMID- 30212017
TI  - [Oxalate nephropathy due to malabsorption syndrome].
AB  - Enteric oxalate nephropathy is caused by hyperoxaluria. Factors which contribute
      to excessive oxalate absorption are an abundance of free fatty acids in the
      intestine due to malabsorption, changes in the microbiome, and bowel
      inflammation. We present two cases that illustrate different pathophysiological
      aspects of this disease. The first patient was a 70-year-old male who developed
      oxalate nephropathy through malabsorption caused by chronic pancreatitis. It is
      plausible that the oxalate nephropathy was set off by antibiotic treatment which
      influenced the microbiome. The second patient was a 63-year-old male who
      underwent a Roux-en-Y gastric bypass. The associated malabsorption resulted in
      oxalate nephropathy. Kidney biopsies from both patients showed typical oxalate
      crystals. Therapeutic regimens using calcium supplementation, steroids, and a low
      oxalate diet are rational treatments, which have proven to prevent deterioration
      of renal function in some patients.

PMID- 30212018
TI  - [How to read a qualitative research paper?]
AB  - Many readers of medical journals are trained in the 'quantitative approach'. This
      can therefore lead to the misinterpretation of results from qualitative research.
      By considering four key points, readers can interpret a qualitative paper. The
      chosen research method should fit the research question. Within medicine, the
      most common types of qualitative research are: (a) in-depth interviews, (b) focus
      groups, (c) participating observation, and (d) document analysis. The researchers
      should sufficiently describe their own role in the study. The results should be
      illustrated with quotes from study participants. The research should be conducted
      in a technically correct manner. Certain characteristics will highlight this,
      such as iterative data collection and saturation, the latter meaning that data
      collection was discontinued when no new insights or themes were identified
      anymore. The conclusion should be drawn from results obtained within the study. A
      common error made by researchers is to interpret the results from a qualitative
      study in a quantitative manner.

PMID- 30212019
TI  - [Current medical curricula neglect the basic sciences].
AB  - Studying the pre-clinical foundations of the medical profession sharpens the
      mind, improves critical thinking skills, builds academic stamina, and stimulates
      scientific curiosity. However, incorporation of the ever-growing clinical
      knowledge body into medical curricula jeopardizes the time undergraduate medical
      students are exposed to covering the basic sciences. In addition, clinical
      practice guidelines and clinical protocols lessen the importance of fostering
      critical thinking skills in our students. Inasmuch as mastering basic sciences
      demands a substantial time consuming intellectual effort, medical students prefer
      memorization and reproduction tasks to analysing challenging basic science
      questions. These three factors increase the risk of training (future) generations
      of doctors less well equipped to manage complex patients and lacking the
      essential knowledge and academic inquisitiveness to advance health care and
      medicine.

PMID- 30212020
TI  - [Prometheus and liver regeneration: the dissection of a myth].
AB  - Prometheus was punished by Zeus because he stole fire to give back to mankind. He
      was chained to a rock in the Caucasus Mountains, and every day an eagle came and
      ate part of his liver. Each night, his liver would regrow, which meant he had to
      endure his punishment for eternity. The myth of Prometheus has inspired artists
      and scientists alike; in medicine, it has become the symbol of the regenerative
      capacity of the liver. For the liver surgeon, liver regeneration has become an
      indispensable ally. Did the ancient Greeks already have knowledge of the liver's
      ability to restore itself and of the fact that this capacity is inexhaustible?

PMID- 30212021
TI  - [Preconception care in 2018; still too many missed opportunities].
AB  - Good preconception care does not only benefit the health of the mother to be and
      her child during pregnancy, but also their health in later life. In the
      Netherlands, preconception care is not standard care. Preconception care aims to
      prevent biomedical, behavioural and social risks by taking steps before
      conception to reduce the likelihood of these risks materialising. It also helps
      mothers to be to make informed reproductive choices. Caregivers and the public
      are not aware enough of the extent in which the first 10 weeks of pregnancy
      affect the health of the infant and of the child later in life. Nowadays,
      antenatal care often starts around 8 weeks of pregnancy, by which time it is too
      late to influence potential risks since embryonic development and placentation
      start immediately after conception. Therefore, all young men and women need to be
      offered preconception care.

PMID- 30212022
TI  - [A step-up approach for dealing with rectal foreign bodies].
AB  - Patients visiting a hospital with retained rectal foreign bodies can no longer be
      considered rare and the incidence appears to increase. Currently, little is known
      about management of patients with retained foreign bodies and there are no
      medical protocols for situations like this. There is no limit to the type of
      objects inserted into the anal canal, exposing clinicians to diagnostic and
      therapeutic dilemmas. Standardised algorithms for patients with retained foreign
      bodies are needed to avoid serious complications such as perforation or
      peritonitis. In this article, we present a 59-year-old, 57-year-old and 29-year
      old male who visited the emergency department with inserted rectal foreign bodies
      and we propose a stepwise approach for dealing with retained rectal foreign
      bodies.

PMID- 30212023
TI  - [An active medical intern with a painful lower leg].
AB  - A 23-year-old female athlete presented with progressive pain in her right lower
      leg since 3 months. Conventional radiography did not reveal a fracture. However,
      a CT-scan showed a proximal posteromedial tibial stress fracture, matching with
      the localisation of the pain.

PMID- 30212024
TI  - [Headache: consider cavernous sinus thrombophlebitis].
AB  - A 38-year-old woman presented with a 1-week history of progressive headache and
      acute onset of left-sided hemiparesis. Neurological examination showed
      bradyphrenia and intermittent left hemiparesis. Brain neuroimaging revealed
      cavernous sinus thrombosis, subdural empyema, pathological vessel-wall
      enhancement of the right middle cerebral artery and ischaemia in the right
      striatum. Cavernous sinus thrombophlebitis with secondary vasculitis and
      ischaemic stroke was diagnosed. Bacteraemia due to Streptococcus intermedius from
      a jaw infection was found and she received antibiotic treatment. At six-month
      follow-up, her symptoms had improved remarkably. Clinical signs such as
      progressive headache, which does not respond to analgesics, subtle cranial nerve
      palsy and increased infectious parameters should alert the clinician to conduct
      appropriate neuroimaging studies. Early initiation of effective antibiotic
      treatment in these cases is essential and can change the course of the illness
      and improve prognosis.

PMID- 30212025
TI  - [Use of the digital stethoscope in medical teaching].
AB  - In teaching physical examination as part of our medical training, we have
      recently started using a digital stethoscope that is connected to external
      speakers. The use of speakers enables students to listen to auscultation in real
      time. This facilitates the direct interpretation, explanation and discussion of
      auscultatory findings. We expect that this interactive method of teaching will
      improve the auscultatory skills of students.

PMID- 30212026
TI  - [Need for a uniform clinical placement quality cycle].
AB  - OBJECTIVE: To investigate how quality control of clinical placements in the
      Netherlands is organised, which tools are available for this purpose, and what
      Dutch clinical placement students think about current clinical placement
      assessment. DESIGN: Document analysis, literature search and questionnaire.
      METHOD: In 2017, we asked all 8 medical schools to share their procedures and
      tools for assessing clinical placement quality with us. We searched various
      databases to find all published tools developed to measure clinical placement
      quality. In the same year, we also conducted a survey of 15 clinical placement
      students per school with questions about current and desired clinical placement
      assessment. RESULTS: All 8 schools sent detailed information about clinical
      placement quality assessment contents and procedures. All schools indicated that
      they are cyclically measuring each clinical placement's quality using evaluations
      by the clinical placement students. Each school uses its own questionnaire, none
      of these questionnaires have been validated. Literature search only found two
      tools specifically developed for assessing clinical placement quality, none of
      which have been validated for the Dutch language and situation. Clinical
      placement students feel that not enough noticeable improvement actions are being
      taken as a result of their evaluations. They preferred a short, uniform
      questionnaire with questions about clinical placement content, atmosphere and
      organisation. CONCLUSION: The quality cycle of clinical placements in the
      Netherlands could be improved with respect to uniformity and implementation of
      actions for improvement. There is a need for standardisation of the clinical
      placement quality cycle and for development of a validated Dutch measuring tool
      for this.

PMID- 30212027
TI  - [The different forms of IgG4-related disease].
AB  - Immunoglobulin G4-related disease (IgG4-RD) is a newly recognised immune-mediated
      disease of unknown origin. IgG4-related disease predominantly affects the
      pancreas (autoimmune pancreatitis type 1), biliary tract (IgG4-associated
      cholangitis) and salivary glands. However, based on distinct histopathological
      findings, IgG4-RD has also been described in nearly every organ of the human
      body. Patient characteristics include elevated IgG4 serum levels, massive
      infiltration of lymphocytes - in particular IgG4-positive B and plasma cells - in
      affected tissues and a good response to immunosuppressive treatment. If left
      untreated, the chronic inflammation associated with IgG4-RD may lead to fibrosis
      and organ failure. Here, we discuss diagnostic challenges in two patients who
      were ultimately diagnosed with IgG4-RD. Additionally, we make suggestions on when
      to consider a possible diagnosis of IgG4-RD and how to approach the patient, thus
      enabling early diagnosis and treatment.

PMID- 30212028
TI  - [It is not an issue that basic science courses are vanishing from the medical
      curriculum].
AB  - There is some controversy regarding the role of and time devoted to so-called
      basic sciences in the medical curriculum. In this article, the author argues that
      nowadays basic sciences are a far less important element of the medical
      curriculum than in the past, and that in time they will likely be phased out
      completely. Arguments put forward are the changing role of the medical doctor,
      evidence that general clinical reasoning skills do not exist, and that the
      contrary assumption has led to havoc. He concludes that the removal of basic
      sciences from the medical curriculum will be substituted by teaching of
      consultation skills, psychology and guideline application.

PMID- 30212029
TI  - ANSI/ASSE Z244.1 (2016): Bringing the Latest Practices to Lockout/Tagout and
      Alternative Methods: The 2016 standard was written to be scalable to meet the
      needs of both large and small companies with varying levels of technology present
      in their machinery and processes.

PMID- 30212030
TI  - Lockout/Tagout: Making Sure Your Organization is All In: When it comes to LOTO, a
      worker may not expend the effort to get critical information or supplies if he
      has to go more than 20 steps or wait more than 10 seconds. This is especially
      true when there is intrinsic motivation to "help" the team.

PMID- 30212031
TI  - Four Questions to Shape Performance: Which behavior would make the biggest
      difference in yielding the results you need?

PMID- 30212032
TI  - More Productive Leadership by Batching and Sequencing: Dividing attention through
      multitasking can increase slips/trips/falls, and also contribute to soft-tissue
      injuries, driving accidents, caught by/between, struck by problems, and many
      more.

PMID- 30212033
TI  - [Seroepidemiological Studies on Pertussis, Diphtheria and Tetanus among Nursing
      Students Enrolled between 1994 and 2011 in the Kitakyushu District].
AB  - Seroepidemiological studies on pertussis, diphtheria and tetanus were performed
      on 1,540 nursing students enrolled in S-university between 1994 and 2011.
      Antibody titers against pertussis toxin (PT) and filamentous hemagglutinin (FHA),
      diphtheria antitoxin titer, and tetanus antitoxin titer were measured using sera
      taken during enrollment. The antibody-seropositive rates and geometric mean
      titers (GMTs) were calculated by according to birth year (1975-1993).The
      pertussis anti-PT and anti-FHA antibody-seropositive rates (seropositive levels
      were both defined as >=10 EU/mL) were 12%-53% and 47%-84%, respectively. The anti
      PT antibody-seropositive rate was lower than the anti-FHA rate. The anti-PT
      antibody GMTs were 2.0-11 EU/mL, whereas the anti-FHA antibody GMTs were 10 EU/mL
      or more (8.8-31 EU/mL) in almost every group. The diphtheria antitoxin
      seropositive rate (>=0.1 IU/mL) was 49%-79%, and the GMT was nearly 0.1 IU/mL.
      The tetanus antitoxin-seropositive rate (>=0.01 IU/mL) was 91%-100%, and the GMT
      was 0.3 IU/mL or more for all the groups.While the nursing students' diphtheria
      and tetanus antitoxin levels were sufficient to prevent both diseases, the anti
      PT antibody-seropositive rate and the GMT were both lower than the level required
      to prevent pertussis, suggesting that many of the nursing students were pertussis
      susceptible. These findings suggest a need for pertussis vaccination in young
      adults or early adolescents.

PMID- 30212034
TI  - [Increase in Bacillus spp.-positive Blood Culture Specimens Linked to Inadequate
      Linen Management].
AB  - Bacillus cereus is a gram-positive rod-type bacterium that forms endospores and
      is distributed throughout various environments. It rarely causes disease in
      humans except for cases of food poisoning. However, infection with B. cereus in
      newborns and immunocompromised individuals can cause severe sepsis. Inappropriate
      catheter insertion and environmental contamination, including that of linen, are
      thought to be routes of transmission. Pseudo-outbreaks of B. cereus caused by
      poor hospital linen management have been reported and are important issues in
      hospitals. The number of Bacillus spp.-positive blood culture specimens increased
      in "A" ward of our hospital. Consequently, the hospital's infection control team
      was asked to determine the cause of the increase.We performed environmental
      research in the "A" ward and the entire hospital. In addition, we investigated
      the current status of B. cereus derection in five core hospitals in the North
      Tohoku region.In our hospital, B. cereus was detected in towels before use. When
      the timeline of contamination was investigated, we found that the towels had
      already been contaminated at the time they were delivered to our hospital. The
      linen washing contractor was unconcerned with laundry disinfection. As a result
      of our findings, disposable towels were introduced. This resulted in a decrease
      in Bacillus spp.-positive blood culture specimens. Among the five core hospitals
      in the North Tohoku region, the hospitals outsourcing laundry to contractors
      without bacteriological monitoring had a significantly higher rate of B. cereus
      positive blood cultures than those of three other hospitals with infection
      control policies for towel management.The increase in Bacillus spp.-positive
      blood culture specimens in our hospital was a result of towel contamination.
      Based on these findings, we suggest that proper linen management(including that
      of towels) is crucial for infection control as well as the quality control of
      bacteriological tests.

PMID- 30212035
TI  - [Effectiveness of Influenza Vaccine in Adults Using A Test-negative, Case-control
      Design --2013/2014 and 2014/2015 Seasons--].
AB  - The influenza vaccine forms the basis of efforts to prevent the occurrence of
      influenza virus infection. However, vaccine effectiveness (VE) differs every
      season, which complicates efforts to combat the spread of infection. To develop a
      robust method to analyse variations in VE, we assessed VE among adult patients
      with influenza using a test-negative, case-control study design that evaluated
      vaccination records and the corresponding results of rapid influenza diagnostic
      tests during the 2013/14 and 2014/15 influenza seasons.During the 2013/14season,
      the adjusted VEs against influenza A and B viruses were 54.9% (95% confidence
      interval [CI] = 24.2% - 73.2%) and 56.6% (95% CI = 19.1% - 76.7%),
      respectively.In contrast, during the 2014/15season, the adjusted VE against the
      influenza A (H3N2), virus was -2% (95% CI = -66% - 37.5%). Moreover, only a few
      patients were infected with the influenza B virus, thus, the VE against influenza
      B could not be assessed.The low VE during the 2014/15 season could be attributed
      to antigenic drift in the circulating influenza A (H3N2) viruses and mutations in
      the egg-adapted vaccine strains.Estimation of the VE against the influenza virus
      using this test-negative, case-control study design was simple and easy, and this
      study design had a precision similar to that of a randomized control
      trial.Therefore, this study design could be employed to predict VE through out
      the influenza season and may be used as the basis of influenza prophylaxis.

PMID- 30212036
TI  - [Decreasing Susceptibility of MRSA to Daptomycin During the Course of Treatment].
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) with decreased susceptibility
      to daptomycin (DAP) were isolated from 4 patients receiving DAP from November
      2013 to May 2014. These patients were treated with DAP for more than 7 days in
      all the cases. The pulsed-field gel electrophoresis (PFGE) patterns for MRSA
      isolates recovered from each patient pre- and post-DAP therapy were identical.
      Sequencing of mprF detected 2 amino acid substitutions (T345I or L826F) in 2 of
      the isolates. These results suggest that in vivo MRSA was resistant to DAP during
      DAP therapy. Furthermore, the MICs for DAP can vary by+/-1 dilution depending on
      the susceptibility test. When testing DAP susceptibility, there is a need to
      monitor reproducibility using different susceptibility tests, including the CLSI
      method.

PMID- 30212037
TI  - [Response to Ebola Virus Disease Outbreak: Experience in Field Epidemiology in
      Sierra Leone].
AB  - The Ebola virus disease (EVD) outbreak that occurred in West Africa in 2014 was
      the largest ever in the world. In Sierra Leone, the number of cases reported
      peaked in December 2014 and gradually declined. However, the outbreak was not
      immediately terminated. To support the response of the World Health Organization
      (WHO) to EVD, the WHO Western Pacific Regional Office established the Western
      Pacific Ebola Support Team (WEST) with the aim of eliminating EVD in Port Loko
      District, where a certain number of new cases were still being reported in March
      2015. We were dispatched to join WEST as WHO short term consultants in
      epidemiology for about six weeks from March to June 2015. Here, we describe our
      activities in the field as epidemiologists to show how Japan can contribute in
      the area of epidemiology during infectious disease outbreaks of international
      concern.The analysis suggested that the surveillance data for all the deaths and
      suspected EVD cases were underreporting the actual number of EVD cases in Port
      Loko District. Although contact tracing was conducted, new EVD cases were often
      found among untraced contacts because of inadequate information from residents or
      insufficient investigation by the contact tracing team. In addition, incomplete
      monitoring of the health status of close contacts resulted in secondary
      transmission of the disease. Data managers established a database by centralizing
      data from the surveillance and contact tracing teams, laboratories, and
      healthcare facilities. The number of deaths per week recorded by these data
      sources was lower than the number of deaths per week that would be expected from
      the national mortality statistics. The team strengthened surveillance and social
      mobilization in the regions with wide disparities between the actual and reported
      numbers of deaths.For the on-the-ground activities, the field coordinator,
      epidemiologists, and social mobilizers, as well as the logistic and
      administrative support personnel, were all indispensable in supporting the field
      investigation of these infectious disease outbreaks of public health concern. A
      field coordinator, in particular, requires outstanding knowledge, experience and
      skills to lead team operations in liaison with international and local partners
      and to build confidence among local residents. The development of these human
      resources and the maintenance of a response team are required for potential
      future outbreaks, and this is an important area that Japan could prepare for and
      then contribute to future outbreaks. This report does not represent an official
      view of the WHO or our affiliates.

PMID- 30212038
TI  - An important perspective on the recent history of leprosy - and its implications
      for the current Global Strategy.

PMID- 30212039
TI  - [Laboratory Diagnosis of Human Adenovirus for Surveillance in Japan in 2014].
AB  - Objective: This study sought to clarify how laboratory testing of human
      mastadenovirus (adenovirus) is conducted in local public health institutes (LPHI)
      as part of Japanese adenovirus surveillance. Methods: Questionnaires on
      adenovirus surveillance were distributed to LPHIs (n=77) between February and
      May, 2014. Results: The participation response rate was 100%. During this period,
      adenoviral cultures were conducted at 65 institutes (84%) while 49 (64%) used
      neutralization testing. PCR diagnoses were conducted at 58 institutes (75%). The
      national adenovirus diagnosis manual (http://www.nih.go.jp/niid/ja/labo
      manual.html), which includes methods of viral culture and PCR for penton, hexon,
      and fiber-coding regions, was used in 68% of the LPHIs. Ocular samples were
      diagnosed at 36 (47%) LPHIs. Conclusion: Most LPHIs conduct adenovirus
      surveillance in accordance with the national diagnosis manual. Both PCR and viral
      cultures were used for adenovirus surveillance in the majority of LPHIs during
      the surveyed period.

PMID- 30212040
TI  - Need for, and acceptability of, rapid diagnostic tests that can facilitate the
      diagnosis of leprosy.
AB  - New cases of leprosy indicate that M. leprae transmission is continuing. In the
      first half of 2015 we sequentially diagnosed new leprosy patients attending Cebu
      Skin Clinic, a referral and leprosy treatment centre in Cebu City, Philippines.
      The great majority of patients were characterised as multibacillary (145 of 147;
      98.6%), most of whom had bacterial indices 3p (86; 58.5%) or more than 20 skin
      lesions (94; 63.9%). Importantly, 65.3% estimated that slightly over a year had
      elapsed between their initial symptoms and diagnosis, while 26.5% reported a
      lapse of greater than 3 years. Many patients (73.8%) and their household contacts
      (79.2%) reported that their lives had already been adversely affected. This
      indicates thatimprovements to expedite diagnosis are required, and rapid
      diagnostic tests (RDT) appear suited for this. Questionnaires were conducted
      among various groups to ascertain the acceptability and perception of RDT. All
      groups responded favourably, with 95.9% patients, 93.2% contacts and 81.4% of the
      general population responding that RDT would be beneficial for leprosy. The vast
      majority of patients (88.6%) indicated that they would 'definitely' submit to
      testing, followed by 69.4% of contacts and 72.2% of the general population. The
      majority of patients thoughttheir household members should also be tested, while
      a subset indicated that RDT use should be extended to their respective
      communities. We propose that, due to their ease of use, point of care
      applicability and acceptability within target populations, RDT could be used as
      an entry point to inform the diagnostic process for leprosy.

PMID- 30212041
TI  - [Kaposi's Sarcoma Herpesvirus-associated Inflammatory Cytokine Syndrome (KICS)
      Improved by Antiretroviral Therapy in an HIV-infected Patient].
AB  - We report a case of a 63-year-old HIV-positive Japanese male with a CD4 cell
      count of 127/MUL who was admitted to our hospital because of suspected malignant
      lymphoma. Initial blood tests revealed anemia, thrombocytopenia, hypoalbuminemia,
      and hypergammaglobulinemia. Imaging tests revealed a lung nodule, bilateral
      pleural effusion, hepatosplenomegaly and generalized lymphadenopathy. No evidence
      of malignant lymphoma or multicentric Castleman's disease was noted on biopsy
      specimens; however, Kaposi sarcoma-associated herpesvirus (KSHV)-encoded latency
      associated nuclear antigen-1-positive cells were observed as well as an elevated
      interleukin (IL)-6, IL-10 and KSHV viral load. He fulfilled the novel diagnostic
      criteria for KSHV-associated inflammatory cytokine syndrome (KICS). After
      initiating antiretroviral therapy, his symptoms and radiological abnormalities
      drastically improved. After 1-year follow-up, his HIV was well controlled without
      any relapsing symptoms.

PMID- 30212042
TI  - [Safety and Adverse Events Following Measles, Mumps, and Rubella (MMR)
      Vaccination in Adults in Japan].

PMID- 30212043
TI  - Outcome of 6 months MBMDT in MB patients in Bangladesh- preliminary results.
AB  - Introduction: Duration of leprosy treatment remains long and difficult to
      complete in resource poor areas. Studies suggest that shortening duration of
      therapy for MB patients to 6 months may be possible. Methods: New MB patients in
      2005 in two NGO projects in Bangladesh were treated with 6 months WHO MB MDT and
      the rate of relapse and fall in BI on slit skin smear during follow up to date
      were compared with a control group treated for 12 months the previous year.
      Results: 1612 patients were enrolled in the trial, and the average duration of
      follow up was over 7 years after diagnosis. During 11,425 PYAR of follow-up, no
      relapses were detected, by bacteriological or clinical criteria, in the 918
      patients in the 6 months MB MDT group, nor in the 694 patients in the control
      group. Rate of declineof BI in those who were smear positive was not
      significantly different between groups. Conclusion: The data does not suggest
      that shortening duration of treatment from 2 months to 6 months MDT for MB
      leprosy patients leads to increased rates of relapse.

PMID- 30212044
TI  - [Sensitivities of Respiratory Syncytial Virus Antigen-detection Kits Commercially
      Available in Japan].
AB  - Respiratory syncytial virus (RSV) antigen-detection kits are used in clinical
      settings in Japan. Here, we compared the sensitivities of 12 different kits that
      are commercially available in Japan. Notably, these kits were developed based on
      the principle of immunochromatography. The comparison was performed using six
      different test specimens:standard laboratory strains of RSV subgroups A and B,
      and clinical specimens of nasal aspirates from patients infected with RSV
      subgroups A or B. The specimens were serially diluted with medium at half log
      concentration, and the dilutions were applied to the kit tests. The minimum
      detection limit was determined for each kit and for every specimen by
      investigating the maximum dilution rate for acquiring positive result. The
      absolute minimum detection limits were calculated based on the viral RNA copy
      number of the specimens and the maximum dilution rate ranged from 107 to 109
      copies/mL, depending on the specimens and kits. Thus, the sensitivity was
      revealed to differ among the viral specimens examined using each kit and among
      the kits used to examine each viral specimen, though the difference was not
      significant and revealed a maximum of only 10 times. The results were compared
      with the geometric mean values of the results for all 12 kits which were
      separately calculated for all 6 specimens. Consequently, some kits with lower or
      higher sensitivities to all the tested specimens were identified, suggesting that
      some general differences in sensitivity exist among commercially available RSV
      antigen-detection kits, although the differences are not significant. Of course,
      selecting kit with a higher sensitivity would be preferable, but no large
      differences in sensitivity among the available kits examined in the current
      study. Therefore, other factors such as cost-effectiveness, convenience, time
      required for testing, etc., can be taken into account when selecting a kit for
      use in clinical settings.

PMID- 30212045
TI  - [Retrospective Study of Clinical Features and Prognosis of Pneumococcal Pneumonia
      Among Patients Under 65 Years of Age].
AB  - The 23-valent pneumococcal polysaccharide vaccine (PPSV23) for elderly people has
      been included in the National Immunization Program (NIP) of Japan since October
      2014. Targets for PPSV23 were restricted to persons >=65 years of age and persons
      60 to 64 years of age with an underlying severe physical disability (expressed as
      1st grade in Japan). In this study, the clinical courses of non-target persons
      <65 years of age were compared between those with non-severe underlying diseases
      (A group) and those without underlying diseases (B group), and the need to expand
      the targets for PPSV23 within the NIP was investigated. Persons with pneumococcal
      pneumonia who were diagnosed based on a positive sputum or blood culture result
      were enrolled between January 2004 and April 2014. As a result, the number of
      subjects in A group was 2.6 times larger than that in B group, and this
      difference was especially pronounced (4.2 times) among subjects between the age
      of 60 to 64 years. These findings suggest that persons with underlying disease
      without a 1st grade physical disability might also be susceptible to pneumococcal
      pneumonia. No significant differences in the severity of pneumonia, the length of
      treatment, or the rates of admission were seen between A group and B group. The
      severity of pneumonia and the rates of admission among targets of the NIP were
      significantly higher than those of A group. In conclusion, our study suggests
      that A group should also be included among the targets of the NIP and that all
      targets eligible to receive the pneumococcal vaccine within NIP should be
      inoculated.

PMID- 30212046
TI  - Spatial and temporal trends in new case detection of leprosy in India.
AB  - Background: India achieved the goal of 'leprosy elimination' by reducing the
      burden of leprosy to less than one case per 10,000 inhabitants in 2005. Sustained
      and committed efforts by national programmes have led to a decline in the burden
      of leprosy to a great extent. Purpose: To examine the spatial clustering of
      leprosy case detection and spatiotemporal trend using Bayesian space period
      model. Materials: The National Leprosy Eradication Programme (NLEP) data of
      annual new case detection of leprosy in 34 districts of Maharashtra for eight
      data years 2007-08 to 2014-15. Methods: The presence of spatial dependency was
      assessed using the case detection rate for each of the eight data years spanning
      from 2007-2015 using Moran's I statistic and the variation over space and time
      was modeled using the Bayesian Space Period model. Results: The Moran's I value
      was found to be statistically significant for each of the time period. The period
      effect was significantly higher than the average in the year 2007(4%), 2009(5%),
      2011(6%), 2013(18%) and significantly lower than the average in 2008(7%),
      2010(4%), 2012(11%), 2014(9%). The spatial effects varied between0.579 and 1.52.
      There was a higher risk of leprosy (50% or more) found in districts of
      Garhchiroli, Raigad and Warda. The lowest risk of 0.579 was observed in the
      Nagpur district. Conclusion: The period effect of new case detection of leprosy
      using the SP model, measured in terms of relative risk shows a seesaw effect at
      work in districts of Maharashtra. The alternate jump in the risk of leprosy given
      by the model could be the actual scenario or due to expended activities in the
      study area. Further in depthinvestigation needed to ascertain the facts.
      Observing the spatial Bayesian effect districts Garhchiroli, Raigad and Warda are
      at greater risk and need priority care.

PMID- 30212047
TI  - [Clinical Characteristics of Adult Onset RSV Infection During Two Consecutive
      Winter Seasons].
AB  - We performed a retrospective study examining adult patients with RSV infection
      who were diagnosed at our hospital during two consecutive winter seasons, 2011
      2012 and 2012-2013; these patients were compared with, adult patients who had
      been diagnosed as having influenza during the same periods. RSV infection was
      confirmed by a 4-fold increase in the CF antibody titer, while influenza was
      diagnosed based on a rapid antigen test. Forty-three patients with RSV infection
      and pneumonia patients (39 inpatients and 4 outpatients) and 25 patients with
      influenza and pneumonia (23 inpatients and 2 outpatients) were detected. Overall,
      54 patients with RSV infection and 42 patients with influenza, were hospitalized
      during the two seasons. A history of the influenza vaccination was verified for
      48% of the influenza patients with pneumonia and 35% of the non-pneumonia
      influenza patients who were hospitalized, and neuraminidase inhibitors were used
      for the treatment of all the influenza patients and 88% of the non-pneumonia
      influenza patients who were hospitalized. Overall, 5.3% of the adult cases with
      pneumonia (43/817) during the two seasons were diagnosed as having RSV related
      illness, and within the peak period, in particular, 14.6% were judged as having
      RSV pneumonia. Furthermore, 63% of the patients with RSV infection and pneumonia
      had mixed infections with other common respiratory pathogen, such as
      Streptococcus pneumoniae, and within the peak period, almost 15% of the patients
      with pneumonococcal pneumonia were confirmed to have mixed infections that
      included RSV. In both groups, one-fourth of the patients had been living in
      nursing homes or had been receibing home medical care. Up to 20% of the RSV
      pneumonia patients were initially diagnosed as having aspiration pneumonia. We
      suspect that some of these elderly patients might have developed pneumonia as a
      result of preceding viral infection or following vomiting or aspiration. The
      overall clinical picture, such as the mean age, maximum body temperature,
      hypoxemia, CRP, and WBC, did not differ significantly between the two groups. The
      30-day mortality and overall hospital mortality rates were similar in both
      groups, but the lengths of the hospital stay were significantly longer, and
      several patients survived but continued to have a reduced activities of daily
      living score at the time of their discharge in the RSV pneumonia group.

PMID- 30212048
TI  - [Molecular Characterization of Salmonella enterica subsp. enterica Serovar 4: b: 
      ].
AB  - Salmonella is a major causative agent of food borne diseases. Recently,
      monophasic strains of Salmonella, such as S. enterica 4: i: -, have been
      frequently reported. Here, we investigated the genetic background of S. enterica
      4: b: - using multilocus sequence typing (MLST) and pulsed-field gel
      electrophoresis. A total of 10 strains of S. enterica (I) 4: b: - were examined
      and compared with 34 strains including serovar Paratyphi B and Paratyphi B var
      Java, Schleissheim, and II b: -. All I 4: b: - strains were negative for hin
      which encodes an invertase that converts the H phases, and six were also negative
      for fljB, which encodes the second phase of the H antigen. An MLST analysis
      identified 12 sequence types (ST) and 6 ST complexes (STC) from the 44 strains. A
      clustering analysis of PFGE patterns almost corresponded to the STC. The
      monophasic I 4: b: - strains were assigned to 3 STCs (19, 32 and 155),
      corresponding to those of Paratyphi B var. Java or a monophasic strain according
      to the data of this and previous studies. These findings suggest that the
      monophasic strains examined in this study might have been derived from multiple
      clones of Paratyphi B var Java. This study shows the usefulness of molecular
      typing as complementation tools of the conventional serotyping system.

PMID- 30212049
TI  - [A Case of Blackwater Fever after Treatment for Plasmodium falciparum Malaria].
AB  - Blackwater fever (BWF), which causes massive intravascular hemolysis and the
      passage of black-colored urine, is a poorly understood condition that is rarely
      seen during the course of malaria. Here, we present a case of BWF that developed
      after treatment for falciparum malaria complicated by hyperparasitemia in a
      Japanese traveler.A 29-year-old woman returning from Ghana visited our travel
      clinic with complaints of sudden fever and headache on the third day of illness.
      She had taken anti-malarial drugs for intermittent malaria prophylaxis and the
      treatment of malaria while in Ghana. Falciparum malaria was diagnosed based on
      the results of a blood smear and was confirmed using PCR. She was successfully
      treated with a single artesunate suppository and one dose of intravenous quinine
      followed by artemether-lumefantrin for 3 days. She was discharged without
      complications on the 11th day of illness. However, she was re-admitted for fever
      and headache on the 16th day of illness. The recrudescence of malaria was
      excluded by peripheral blood smear results. BWF was diagnosed based on the
      presence of fever, black-colored urine, and laboratory findings suggesting
      intravascular hemolysis. She was treated with supportive care, including the
      transfusion of 10 packs of red blood cells and the maintenance of fluid and
      electrolyte balance, and she gradually improved within two weeks.BWF is a rare
      but severe complication induced by severe falciparum malaria and/or the use of
      the aryl-amino alcohol group of antimalarial drugs. Thus, consideration of BWF is
      particularly important for a rapid and accurate diagnosis.

PMID- 30212050
TI  - [A Case of Brain Abscess Caused by Nocardia farcinica in which the Test Results
      for Drug Susceptibility Conflicted with the Actual Clinical Course].
AB  - Sulfamethoxazloe-trimethoprim is one of the most frequently used antibiotics in
      the treatment of Nocardia infection. However, in vitro studies have shown an
      increase in sulfonamide resistance among Nocardia species. Here, we present a
      case with a brain abscess caused by Nocardia farcinica in which the test results
      for drug susceptibility to sulfonamide conflicted with the actual clinical
      course.A 74-year-old woman with autoimmune hepatitis who has being treated with
      oral prednisolone (16 mg/day) was admitted because of headaches and fever. A CT
      scan and MRI revealed a brain abscess that had ruptured into the lateral
      ventricle. She was empirically treated with antibiotics, but her condition did
      not resolve. Therefore, the abscess was drained surgically. Gram and Kinyoun
      stains for pus revealed a modified acid-fast branching filamentous bacterium
      consistent with Nocardia species. The pathogen was identified as Nocardia
      farcinica based on its 16S rRNA sequence. Consequently, the patient was treated
      with sulfamethoxazole -trimethoprim and amikacin. However, susceptibility testing
      (broth microdilution method) showed that the strain was completely resistant to
      sulfamethoxazole-trimethoprim. We therefore changed the therapeutic regimen to
      imipenem-cilastatin and amikacin, but her symptoms worsened and the treatment was
      thought to have failed. She was then re-treated with sulfamethoxazole-
      trimethoprim, and her symptoms resolved. Some reports have suggested that
      interpreting the results of Nocardia susceptibility testing may be difficult
      especially the susceptibility of Nocardia to sulfamethoxazole-trimethoprim. The
      present case suggests a confliction between susceptibility testing and the
      clinical course of a patient with Nocardia infection.

PMID- 30212051
TI  - [A Case of Bacteremia Urinary Tract Infection Caused by Stenotrophomonas
      maltophilia in an 8-month-old Boy].
AB  - Bacteremic urinary tract infection (UTI) caused by Stenotrophomonas maltophilia
      rarely occurs in pediatric patients. We report a case of bacteremic UTI caused by
      S. maltophilia in an 8-month-old boy with a congenital ureteropelvic junction
      obstruction on the left side. The patient was brought to our hospital with a
      chief complaint of fever. He had undergone a nephrostomy tube insertion 4 months
      previously, and the tube had been removed 2 weeks before presentation at our
      hospital. He had a white blood cell count of 6,100/MUL and a serum C-reactive
      protein level of 4.51 mg/dL. A microscopic urinalysis and Gram stain showed
      numerous Gram-negative bacilli and many leukocytes, and an ultrasonography showed
      grade 4 hydronephrosis of the left kidney. Based on these findings, we diagnosed
      the infant as having a complex UTI and started the intravenous administration of
      piperacillin/tazobactam. After 2 days, a urine culture showed Gram-negative
      bacilli (107 CFU/mL). Gram-negative bacilli were also cultured from two blood
      samples that were taken from different vessels at the time of admission. The Gram
      negative bacilli were identified as S. maltophilia via the automated bacterial
      identification system. The patient recovered after a 2-week intravenous
      piperacillin/tazobactam treatment and subsequent oral treatment with trimethoprim
      sulfamethoxazole. Since medical devices are susceptible to contamination with S.
      maltophilia, we suspect that the nephrostomy tube was the most likely source of
      infection.

PMID- 30212052
TI  - [A Case of Legionella Pneumonia Causing Neurological Symptoms Related to a
      Reversible Corpus Callosum Lesion].
AB  - A 51-year-old man presented at the emergency department with a one-day history of
      fever, altered mental status, slurred speech, worsening gait instability, nausea,
      vomiting, and diarrhea. The patient did not have a history of alcoholism or drug
      abuse. On physical examination, crackles were heard over the right lower lobe.
      Neurological findings revealed ataxic gait, dysarthria and bilateral dysmetria
      upon finger-nose testing. The results of laboratory tests revealed leukocytosis,
      renal failure, and hyponatremia. Chest radiography and lung computed tomography
      (CT) revealed right lower lobe infiltrates with air bronchograms. The result of a
      urinary Legionella antigen test was positive. The results of brain CT and
      cerebrospinal fluid (CSF) analyses did not reveal any signs of infection, but
      brain magnetic resonance imaging (MRI) revealed a corpus callosum lesion upon
      admission. The patient's symptoms began to resolve after the administration of
      intravenous levofloxacin. A subsequent brain MRI examination performed 9 days
      after admission showed the complete resolution of the lesion. He was discharged
      11 days after admission without any neurological sequelae. He was finally
      diagnosed as having clinically mild encephalitis/ encephalopathy with a
      reversible splenial lesion (MERS).

PMID- 30212053
TI  - Is the WHO disability grading system for leprosy related to the level of
      functional activity and social participation?
AB  - To investigate the relationship between the WHO disability grading system for
      leprosy with the limitations to perform daily functional activities and
      thedecrease in social participation in participants with leprosy. Participants
      with a diagnosis of leprosy were recruited at the dermatology ambulatory clinic
      of the University Hospital of Sergipe. In order to investigate the association of
      WHO disability grading system for leprosy with activities of dailyliving measured
      with the Screening Activity Limitation and Safety Awareness (SALSA) scale and
      with the social participation (P-scale), we performed an analysis with the
      Kruskal-Wallis test and the Spearman coefficient. Thirty-six patients diagnosed
      with leprosy participated in the study. Most ofparticipants had mild to moderate
      daily activity limitations and 58% of participants did not have any restriction
      participation. The findings demonstrated that the WHO grading is associated with
      the level of activity (P < 0.0001; p = 0.58), but not with the level of
      participation (P <0.05; p = 0.27). Although the WHO grading system is used in
      Brazil and worldwide as an epidemiological indicator to explain the burden of
      leprosy, the results of this study demonstrated that in our sample the WHO
      grading system was not associated with participation. Participation is a complex
      construct with the influence of different psychosocial factors. In order to
      determine social participation damage of infectious diseases such as leprosy, it
      is necessary to develop new index of classification based on a broader definition
      of disability. Health professionals should consider the international
      classification of function and health (ICF) to develop such index.

PMID- 30212168
TI  - Experiences with Thalidomide for Erythema Nodosum Leprosum- a retrospective
      study.
AB  - Background: Thalidomide is well known as a steroid sparing drug in Erythema
      Nodosum leprosum (ENL) reaction in leprosy. There is no guideline as to when it
      should be offered to patients. Documentation of ENL presentation with its
      morbidity before and after with patient profile can be a baseline to develop a
      selection criteria asto when thalidomide should be started to reduce steroid
      related morbidly. Method: Chart and electronic record review was done. Result:
      427 ENL patients attended the hospital from 2010 to 2014. 73 patients (67 males
      six females) were treated with thalidomide. 77% (56) patients were in the age
      group of 16-45 yrs. 16% (12) were dependent and 39% (29) were taking steroids at
      presentation. 82% (60) became dependent while on treatment. Ninety five
      percentwere chronic or recurrent ENLs and 73% (53) had moderate to severe ENLs
      over 49 median months. Steroid induced morbidities were (Cushingoid features 42%,
      diabetes 21%, infections GI 42%, genitourinary 26%, cataract 23%). There was 11%
      mortality. Conclusion: Further studies are recommended to diagnose steroid
      dependence earlyto prevent serious adverse effects.

PMID- 30212169
TI  - Autonomic neuropathy impairing quality of life after completion of MDT: Are we
      managing enough?
AB  - A 26 year old male, treated case of lepromatous leprosy, presented with severe
      heat intolerance, loss of sensation and sweating over distal parts of both upper
      and lower limb of 12 years' duration. On examination, there was definite sensory
      loss over the extremities in glove and stocking pattern and thickening of the
      bilateral ulnar, common peroneal and radial nerves. There were three trophic
      ulcers over the plantar aspect of the right foot, atrophy of the small muscles of
      hand, reabsorption of the distal index, middle and ring fingers along with total
      clawing of both hands. A slit skin smear for acid fast bacilli revealed
      fragmented granular bacilli. A starch-iodine test was used to document the
      pattern of sweating whichcoincided with the glove and stocking pattern of sensory
      loss found in lepromatous leprosy. Even though the patient had completed WHO MDT
      and bacilli were dead, the damage to the autonomic system was extensive in the
      patient leading to widespread loss of sweating and severe heat intolerance
      affecting his quality of life. Also the patient had motor deformity in the form
      of total clawing which added to his disability. Therefore all cases should be
      followed up even after completion of MDT, counselled regarding the course of the
      disease, and trained to tackle theconsequences of nerve damage in their daily
      life. We report the case as autonomic dysfunction that has been rarely documented
      in leprosy patients and also we emphasise the use of the starch-iodine test in
      such cases along with management of the disease in part by using hydro-oleo
      therapy.

PMID- 30212170
TI  - Uncommon clinical presentations of leprosy: apropos of three cases.
AB  - Leprosy has been labelled as a great imitator since times immemorial. This mainly
      is because of the wide range of its clinical presentations. In endemic regions it
      is important to entertain the possibility of leprosy even in atypical
      presentations so as to avoid misdiagnosis. Here we report three cases of leprosy
      with uncommon disease presentations. First case had presented with eczematous
      morphology of cutaneous lesions without sensory loss and nerve thickening. Second
      case had localized type-2 reaction and third case had presented initially with
      only rheumatologic manifestations. Histopathology is an important tool in
      arriving at correct diagnosis and thus should be done in all suspected cases.

PMID- 30212171
TI  - Leukemia cutis in a patient of relapsed leprosy- Coincidence or predisposition?
AB  - Leprosy, a disease of skin and peripheral nerves has varied manifestations which
      principally affect the immune status of the host. Leukemic skin infiltrations in
      patients with leukemia are referred to as leukemia cutis. It can be seen in all
      types of leukemia, especially in patients with acute myelomonocytic leukemia
      (AML). In majority of cases, the cutaneous lesions are nonspecific manifestations
      associated with an impaired immune system.1 Though various malignancies have been
      documented with leprosy, no case of borderline-tuberculoid (BT) Hansen's disease
      with coexisting leukemia cutis has ever been reported in literature to the best
      of our knowledge.

PMID- 30212173
TI  - Prevalence of leprosy-related disability in Bangladesh.
AB  - Disability due to leprosy often lasts lifelong, so estimates of the burden of
      leprosy in a community based on 'registered prevalence of leprosy cases' or on
      'proportion with Grade 2 disability amongst new cases in past year' will
      seriously underestimate the number of disabled people in the community needing
      support or services. In a previously highly endemic are of Bangladesh, the
      accumulated prevalence of disability due to leprosy amongst adults was
      45.35/100,000 population.

PMID- 30212172
TI  - Disability aid compliance in people affected by leprosy in urban and rural
      Maharashtra, India - a need for comprehensive study.

PMID- 30212174
TI  - Two-Dimensional NiSe2/N-Rich Carbon Nanocomposites Derived from Ni-Hexamine
      Frameworks for Superb Na-Ion Storage.
AB  - Design of functional carbon-based nanomaterials from metal-organic frameworks
      (MOFs) has attracted soaring interests in recent years. However, a MOF-derived
      strategy toward two-dimensional (2D) nanomaterials remains a great challenge. In
      this work, we develop a layered Ni-hexamine framework as efficient precursor to
      prepare a 2D NiSe2/N-rich carbon nanocomposite by a simple pyrolysis and
      subsequent selenization process. In the 2D NiSe2/N-rich carbon nanocomposite,
      NiSe2 nanoparticles with diameters of ca. 75 nm are homogeneously distributed in
      the N-rich carbon nanosheets. When serving as anode materials for sodium-ion
      batteries, the 2D nanocomposites exhibit a high reversible capacity of 410 mAh g
      1 at 1 A g-1 and maintain a value of 255 mAh g-1 even at 10 A g-1. The excellent
      electrochemical performance can be attributed to the synergistic effects between
      the N-rich carbon nanosheets and NiSe2 nanoparticles. More importantly, the
      hexamine-based MOFs can be regarded as new and powerful platforms for the
      fabrication of 2D N-rich carbon-based nanomaterials, which is of great importance
      for various potential applications.

PMID- 30212175
TI  - Enhanced Bioactivity of Collagen Fiber Functionalized with Room Temperature
      Atomic Layer Deposited Titania.
AB  - Surface modifications of a biomaterial like collagen are crucial in improving the
      surface properties and thus enhancing the functionality and performance of such a
      material for a variety of biomedical applications. In this study, a commercially
      available collagen membrane's surface was functionalized by depositing an
      ultrathin film of titania or titanium dioxide (TiO2) using a room temperature
      atomic layer deposition (ALD) process. A novel titanium precursor-oxidizer
      combination was used for this process in a custom-made ALD reactor. Surface
      characterizations revealed successful deposition of uniform, conformal TiO2 thin
      film on the collagen fibrillar surface, and consequently, the fibers became
      thicker making the membrane pores smaller. The in vitro bioactivity of the ALD
      TiO2 thin film coated collagen was investigated for the first time using cell
      proliferation and a calcium phosphate mineralization assay. The TiO2-coated
      collagen demonstrated improved biocompatibility promoting higher growth and
      proliferation of human osteoblastic and mesenchymal stem cells when compared to
      that of noncoated collagen. A higher level of calcium phosphate or apatite
      formation was observed on ALD modified collagen surface as compared to that on
      noncoated collagen. Therefore, this novel material can be promising in bone
      tissue engineering applications.

PMID- 30212176
TI  - Structure Property-CO2 Capture Performance Relations of Amine-Functionalized
      Porous Silica Composite Adsorbents.
AB  - In order to investigate the influence of support structure properties on CO2
      capture performances of solid amine adsorbents, a novel three-dimensional
      disordered porous silica (3dd) with hierarchical pore networks was developed and
      then compared to other three materials as adsorbent support, namely, hierarchical
      porous silica (HPS), MCM-41, and SBA-15. They were all functionalized with
      tetraethylenepentaamine (TEPA) to prepare CO2 adsorbents. The adsorbents' ability
      to capture CO2 was examined on a fixed-bed reactor. When these supports had 60
      wt% TEPA loading, the amounts of CO2 captured followed the order 3dd > HPS > SBA
      15 > MCM-41 at 75  degrees C; the adsorption capacities were 5.09, 4.9, 4.58, and
      2.49 mmol/g, respectively. The results indicate that a larger pore volume can
      promote the dispersion of amine species to expose more active sites for CO2
      capture. The larger pore size can decrease the CO2 diffusion resistance. High
      surface area is not an important factor in determining capture performance. In
      addition, compared with conventional single-size mesopores, the hierarchical pore
      networks can disperse the TEPA species in different levels of the channel to
      limit undesired loss/aggregation of impregnated TEPA species. Thus, the 3dd
      support exhibits the best stability and highest regeneration conversion compared
      to the other three supports. This work demonstrates that the rational design of
      adsorbent support systems can effectively relieve the trade-off between amine
      loading and diffusion resistance. One method to surmount this trade-off is to
      utilize an adsorbent platform with hierarchical pore networks. Thus, this work
      may provide a feasible strategy for the design of CO2 solid amine adsorbents with
      high capture amount and amine utilization efficiency.

PMID- 30212177
TI  - X-ray-Mediated Release of Molecules and Engineered Proteins from Nanostructure
      Surfaces.
AB  - Many applications call for initiation of chemical reactions with highly
      penetrating X-rays with nanometer precision and little damage to the
      surroundings, which is difficult to realize because of low interaction cross
      sections between hard X-rays and organic matters. Here, we demonstrate that a
      combination of computational protein design of single conjugation site green
      fluorescent proteins and nanomaterial engineering of silica-covered gold
      nanoparticles can enhance the release efficiencies of proteins from the surface
      of nanoparticles. The nanoparticles, to which the proteins are attached through
      DNA linkers, provide increased X-ray absorption without scavenging radicals, and
      single conjugation sites allow efficient release of proteins.

PMID- 30212178
TI  - A Mechanochromic and Photochromic Dual-Responsive Co-assembly with Multicolored
      Switch: A Peptide-Based Dendron Strategy.
AB  - In this contribution, we report a unique co-assembly composed of pyrene and
      spiropyran that were linked separately at the focal point of the same peptide
      based dendron (Phe-Glu), in which the dendrons offer driving forces for the
      coaggregation. A series of co-assemblies with different weight ratios (Py-Phe
      Glu/SP-Phe-Glu) were prepared and the morphology could be tuned. It is found that
      the resulting stable co-assembled organogel is double switchable triggered by
      light and heat. TEM revealed that, in the xerogel, Py-Phe-Glu formed rigid rod
      nanofibers with large diameters and acted as a rigid sketelon where the gracile
      interwoven fibrous structure of SP-Phe-Glu grew. More interestingly, the original
      powder of the co-assembled xerogel (1.0 mg/0.1 mg) not only displayed a
      sequential high-contrast tricolored switch from dark blue to bright cyan and to
      red under external force but also presented multistate accessible photochromic
      properties. Such mechanochromic and photochromic behaviors of the xerogel are
      mainly due to the transition of different excimers of pyrene and the
      force/photoinduced ring-opening reaction of spiropyran. It is rarely reported
      that self-assembled soft materials achieve mechanochromic and photochromic dual
      responsive behaviors with a high-contrast multicolored switch. We believe the co
      assembly strategy based on polypeptide dendrons can be extended to other systems
      for establishing novel intelligent fluorescent materials.

PMID- 30212179
TI  - Composite Multifunctional Micromotors from Droplet Microfluidics.
AB  - Inspired by natural biological machines, lots of effort has been invested in
      developing artificially functional micromotors which can convert energy into
      movement for carrying out tasks in diverse areas. Here, we present a capillary
      microfluidic system with dual inner injections for one-step generation of
      composite structured polymer micromotors with two distinct cores of platinum (Pt)
      nanoparticle-integrated and iron oxide (Fe3O4) nanoparticle-dispersed hydrogels.
      Because the flow rates of the prepolymerized fluids can be precisely tuned in the
      microfluidics, the diameters of the micromotors as well as the sizes and numbers
      of the inner cores can be well tailored to optimize the parameters of the
      resultant micromotors. When exposed to a hydrogen peroxide (H2O2) medium, the Pt
      integrated cores of the micromotors could provide propulsion by expelling bubbles
      produced from the catalytic decomposition of H2O2, while the Fe3O4-dispersed
      cores could impart magnetic guidance for the micromotors. Benefiting from the
      close cooperation of these two types of cores, the micromotors were imparted with
      a strong propulsion and prominent recyclability for the delivery of both
      microscale and macroscale objects. These results manifest that this kind of
      composite micromotor has great diversity in various applications.

PMID- 30212180
TI  - Ultrabroadband Three-Dimensional Printed Radial Perfectly Symmetric Gradient
      Honeycomb All-Dielectric Dual-Directional Lightweight Planar Luneburg Lens.
AB  - An ultrabroadband all-dielectric planar Luneburg lens has been designed and
      fabricated in this study, which is in the form of a radial gradient lightweight
      honeycomb column. Because of the novel design of a radial symmetric honeycomb
      like microstructure in the subwavelength dimension and the radial gradient
      configuration according to the refractive index distribution of Luneburg lens,
      the present lens can focus incident plane waves on the opposite side with high
      convergence, and its operating frequency range is rather broadband, spanning from
      6 to 16 GHz. Besides, the all-dielectric honeycomb-like lens is lightweight with
      a mass density of 0.23 g/cm3, and its broadband transmittance is higher than the
      reported cases consisting of metallic metamaterial or gradient photonic crystal
      structures. A prototype of the lens is fabricated by using 3D printing
      techniques, on which the electric near-field distribution and far-field radiation
      pattern measurements have been carried out, and the aforementioned performances
      were demonstrated experimentally. It was also observed that for two point sources
      placed at the edge of the lens whose intersection angle with the center of the
      lens is 90 degrees , the far-field radiation pattern was still kept highly
      directional, which means that the lens can generate two highly directional beams
      simultaneously, and is an efficient double input-double output device.

PMID- 30212181
TI  - TiO2 Nanowires from Wet-Corrosion Synthesis for Peptide Sequencing Using Laser
      Desorption/Ionization Time-of-Flight Mass Spectrometry.
AB  - In this work, TiO2 nanowires synthesized from a wet-corrosion process were
      presented for peptide sequencing by photocatalytic reaction with UV radiation.
      For the photocatalytic decomposition of peptides, the peptide sample was dropped
      on a target plate containing synthesized TiO2 nanowire zones and UV-irradiated.
      Subsequently, the target plate was analyzed by laser desorption/ionization time
      of-flight (LDI-TOF) mass spectrometry using the synthesized TiO2 nanowires as a
      solid matrix. The feasibility of peptide sequencing based on the photocatalytic
      reaction with the synthesized TiO2 nanowires was demonstrated using six types of
      peptides GHP9 (G1-H-P-Q-G2-K1-K2-K3-K4, 1006.59 Da), BPA-1(K1-S1-L-E-N-S2-Y-G1-G2
      G3-K2-K3-K4, 1394.74 Da), PreS1(F1-G-A-N1-S-N2-N3-P1-D1-W-D2-F2-N4-P2-N5, 1707.68
      Da), HPQ peptide-1 (G-Y-H-P-Q-R-K, 884.45 Da), HPQ peptide-2 (K-R-H-P-Q-Y-G,
      884.45 Da), and HPQ peptide-3 (R-Y-H-P-Q-G-K, 884.45 Da). The identification of
      three different peptides with the same molecular weight was also demonstrated by
      using the synthesized TiO2 nanowires for their photocatalytic decomposition as
      well as for LDI-TOF mass spectrometry as a solid-matrix.

PMID- 30212183
TI  - Persistent Pleural Lesions and Inflammation by Pulmonary Exposure of Multiwalled
      Carbon Nanotubes.
AB  - Translocation of multiwalled carbon nanotubes (MWCNTs) from the lung to the
      pleural cavity, deposition of the fibers in the pleural tissue, induction of
      pleural fibrosis, and mesothelial proliferation have been found in rodents
      administered MWCNTs by different pulmonary exposure methods. However, whether the
      translocation and deposition and the subsequent pleural inflammation are
      associated with the pleural lesions is unclear. In the present study, male F344
      rats were given 250 MUg of two types of MWCNTs, with crocidolite as a positive
      control, 2 times/week for 4 weeks by intratracheal spraying. At 24 h and at 3
      months after the last spraying, the rats were sacrificed for histological
      examination of the lung and chest wall; pleural cavity lavage was also collected
      at sacrifice for observation of pleural inflammatory reactions. The results
      indicated that intratracheally sprayed MWCNTs, like crocidolite fibers,
      translocated into the pleural cavity, deposited in the pleura, and induced
      persistent infiltration of immune cells into the pleural cavity, persistent
      pleural fibrosis, and mesothelial proliferation. The number of MWCNT fibers
      detected in the pleural cavity lavage was parallel to the number of infiltrating
      immune cells, which were mainly composed of macrophages. Analysis of cytokines in
      the fluids of the pleural cavity lavages by suspension array indicated that
      levels of IL-2, IL-18, and IP-10 were significantly increased both at 24 h and at
      3 months after the last spraying. In vitro proliferation assays revealed that a
      mixture of IL-2, IL-18, and IP-10, but not any of these cytokines alone, promoted
      cell proliferation of human fibroblasts and mesothelial cells. These results
      suggest that translocated and deposited MWCNTs induce subsequent pleural
      inflammation and that increased IL-2, IL-18, and IP-10 synergistically promote
      the development of pleural fibrosis and mesothelial proliferation.

PMID- 30212182
TI  - Discrepancies in Kappa Opioid Agonist Binding Revealed through PET Imaging.
AB  - Kappa opioid receptor (KOR) modulation has been pursued in many conceptual
      frameworks for the treatment of human pain, depression, and anxiety. As such,
      several imaging tools have been developed to characterize the density of KORs in
      the human brain and its occupancy by exogenous drug-like compounds. While
      exploring the pharmacology of KOR tool compounds using positron emission
      tomography (PET), we observed discrepancies in the apparent competition binding
      as measured by changes in binding potential (BPND, binding potential with respect
      to non-displaceable uptake). This prompted us to systematically look at the
      relationships between baseline BPND maps for three common KOR PET radioligands,
      the antagonists [11C]LY2795050 and [11C]LY2459989, and the agonist [11C]GR103545.
      We then measured changes in BPND using kappa antagonists (naloxone, naltrexone,
      LY2795050, JDTic, nor-BNI), and found BPND was affected similarly between
      [11C]GR103545 and [11C]LY2459989. Longitudinal PET studies with nor-BNI and JDTic
      were also examined, and we observed a persistent decrease in [11C]GR103545 BPND
      up to 25 days after drug administration for both nor-BNI and JDTic. Kappa
      agonists were also administered, and butorphan and GR89696 (racemic GR103545)
      impacted binding to comparable levels between the two radiotracers. Of greatest
      significance, kappa agonists salvinorin A and U-50488 caused dramatic reductions
      in [11C]GR103545 BPND but did not change [11C]LY2459989 binding. This discrepancy
      was further examined in dose-response studies with each radiotracer as well as in
      vitro binding experiments.

PMID- 30212184
TI  - E-Beam Nanostructuring and Direct Click Biofunctionalization of Thiol-Ene Resist.
AB  - Electron beam lithography (EBL) is of major importance for ultraminiaturized
      biohybrid system fabrication, as it allows combining biomolecular patterning and
      mechanical structure definition on the nanoscale. Existing methods are limited by
      multistep biomolecule immobilization procedures, harsh processing conditions that
      are harmful to sensitive biomolecules, or the structural properties of the
      resulting protein monolayers or hydrogel-based resists. This work introduces a
      thiol-ene EBL resist with chemically reactive thiol groups on its native surface
      that allow the direct and selective "click" immobilization of biomolecules under
      benign processing conditions. We constructed EBL structured features of size down
      to 20 nm, and direct functionalized the nanostructures with a sandwich of biotin
      and streptavidin. The facile combination of polymer nanostructuring with
      biomolecule immobilization enables mechanically robust biohybrid components of
      interest for nanoscale biomedical, electronic, photonic, and robotic
      applications.

PMID- 30212185
TI  - Organo-Aluminum and Zinc Acetamidinates: Preparation, Coordination Ability, and
      Ring-Opening Polymerization Processes of Cyclic Esters.
AB  - The reaction of the highly sterically demanding NNN'-heteroscorpionate
      protioligands pbptamd-H, tbptamd-H, and phbptamd-H (a) and the low sterically
      hindered analogs pbpamd-H, tbpamd-H, and phbpamd-H (b), with 1 equiv of AlR3 (R =
      Me, Et) proceed in high yields to give two families of complexes: the mononuclear
      dialkyl aluminum bidentate-acetamidinates [AlR2(kappa2- N' N')] (kappa2- N' N' =
      pbptamd, R = Me 1, Et 2; tbptamd, R = Me 3, Et 4; phbptamd, R = Me 5, Et 6) and
      the monodentate-acetamidinates [AlR2(kappa2- NN')] (kappa2- NN' = tbpamd, R = Me
      7; phbpamd, R = Me 8, Et 9). In complexes 7-9, the presence of two possible CH-NH
      tautomers as low extended pi-N-C-N'(sp2)-Al and high extended pi-HN-C2-N'(sp2)-Al
      complexes, respectively, could be identified. Moreover, the reaction of aluminum
      dimethyls 7 and 8 with ZnMe2 afforded the isolation of the more stable
      scorpionate zinc monoalkyls [Zn(Me)(kappa3- NNN')] ( NNN' = tbpamd 10 and phbpamd
      11), through a very unusual ligand exchange process, involving a zinc-to-aluminum
      transmetalation of an alkyl group. The X-ray crystal structures of 1, 3, 7, and
      8, as well as that of 11, confirmed unambiguously the different kappa2
      arrangements proposed for bi- or monodentate acetamidinate dialkyls 1-6 and 7-9,
      respectively, the presence of NH tautomer in 7 and 8, and a kappa3- NNN'
      coordination in monoalkyl 11. Density functional theory calculations were used to
      explore the three different favored kappa2-arrangements found in acetamidinate
      aluminum dialkyls 1-9, the relative stability of both CH-NH tautomers, and the
      ligand transfer reaction leading to the formation of kappa3- NNN' zinc monoalkyls
      10 and 11. Interestingly, dialkyls 1, 5, 7, and 8 can act as highly efficient
      single-component living initiators for the ring-opening polymerization of epsilon
      caprolactone and rac-lactide in mild conditions after hours. These initiators
      efficiently mediated the immortal polymerization in the presence of excess of
      benzyl alcohol (up to 20 equiv), as evidenced by the narrow dispersity values and
      the good agreement between the experimental Mn values and monomer/benzyl alcohol
      ratios. In addition, the most sterically hindered initiator, 5, exhibits enhanced
      levels of heteroselectivity on the produced PLAs, reaching Ps values up to 0.70.

PMID- 30212186
TI  - Substrate- to Laterally-Driven Self-Assembly Steered by Cu Nanoclusters: The Case
      of FePcs on an Ultrathin Alumina Film.
AB  - We show that, for the formation of a metallorganic monolayer, it is possible to
      artificially divert from substrate- to laterally-driven self-assembly mechanisms
      by properly tailoring the corrugation of the potential energy surface of the
      growth template. By exploiting the capability of an ultrathin alumina film to
      host metallic nanoparticle seeds, we tune the symmetry of a iron phthalocyanine
      (FePc) two-dimensional crystal, thus showing that it is possible to switch from
      trans to lateral dominating interactions in the controlled growth of an
      organic/inorganic heterostack. Finally, by selecting the size of the metallic
      clusters, we can also control the FePc-metal interaction strength.

PMID- 30212187
TI  - Chemical Mixtures Isolated from House Dust Disrupt Thyroid Receptor beta
      Signaling.
AB  - House dust is a source of exposure to chemicals that can impact hormone
      regulation. This study was designed to evaluate the potential of house dust
      mixtures ( n = 137) to disrupt thyroid hormone nuclear receptor signaling in a
      cell-based reporter assay and to examine associations with thyroid hormones (TH)
      measured in residents of the homes. Approximately 41% of the extracts (ranging
      from 10.5 to 4.097 MUg of dust/mL) significantly antagonized thyroid receptor
      beta (TRbeta) signaling by 20-67% relative to the hormone control. The
      concentrations of 12 flame retardants (FRs) quantified in the mixtures were
      significantly correlated with TRbeta antagonism; however, they were inactive when
      tested individually. We hypothesize that the observed antagonism is due to
      mixture effects or unidentified compounds that co-occur with FRs. Dust extract
      potency was significantly associated with free thyroxine (FT4, rs = -0.64, p <
      0.001), suggesting that more potent dust samples are associated with higher FT4
      levels in residents. Overall, these results suggest that house dust is a
      significant source of exposure to TH-disrupting chemicals, and TRbeta may have a
      role in mediating effects of exposure on TH levels. Additional studies are needed
      to identify the chemical(s) driving the observed effects on TRbeta and to
      determine if these changes lead to any adverse outcomes.

PMID- 30212188
TI  - Proton-Coupled Oxidation of a Diarylamine: Amido and Aminyl Radical Complexes of
      Ruthenium(II).
AB  - Diarylamido, Q-N--Py (L-), complexes of ruthenium(II), trans-[(L
      H+)RuII(PPh3)2Cl2] (1-H+) and trans-[(L-)RuII(PPh3)2(CO)Cl] (2), using N-(5
      nitropyridin-2-yl)quinolin-8-amine (HL) as a ligand are disclosed (Q and Py refer
      to quinoline and 5-nitropyridine fragments). 1-H+ contains a zwitterionic amido
      ligand (Q-N--PyH+) that undergoes a concerted proton electron transfer (CPET)
      reaction in air, generating trans-[(L)Ru(PPh3)2Cl2] (1.CH2Cl2). The ground
      electronic state of 1 is delocalized as [(L-)RuIII <-> (L*)RuII] (L* is an aminyl
      radical of type Q-N*-Py). The 1-H+/1 redox potential depends on the electrolytes,
      and the potentials are -1.57 and -1.40 V, respectively, in the presence of [N( n
      Bu)4]PF6 and [N( n-Bu)4]Cl. The rate of 1-H+ -> 1 conversion depends also on the
      medium and follows the order kD2O-CH2Cl2 > kH2O-CH2Cl2 > kCH2Cl2. In contrast, 2
      containing the corresponding amido (L-) is stable and endures oxidation at 0.14
      V, affording trans-[(L*)RuII(PPh3)2(CO)Cl] (2+). The electronic structures of the
      complexes were authenticated by single-crystal X-ray diffraction studies of HL,
      1.CH2Cl2, and 2.(toluene), EPR spectroscopy, and density functional theory (DFT)
      calculations. Notably, the CQ-N (1.401(2) A) and CPy-N (1.394(2) A) lengths in
      1.CH2Cl2 are relatively longer than the CQ-Namido (1.396(4) A)and CPy-Namido
      (1.372(4) A) lengths in 2.(toluene). Spin density obtained from DFT calculations
      scatters on both N and ruthenium atoms, revealing a delocalized state of 1. The
      notion was further confirmed by variable-temperature EPR spectra of a powder
      sample and CH2Cl2 solution, where the contributions of both [(L-)RuIII] and
      [(L*)RuII] components were detected. In contrast, 2+ is an aminyl radical complex
      of ruthenium(II), where the spin is dominantly localized on the ligand backbone
      (64%), particularly on N (27%). 2+ exhibits a strong EPR signal at g = 2.003. 1
      and 2+ exhibit absorption bands at 560-630 and 830-840 nm, and the origins of
      these excitations were elucidated by TDDFT calculations on 1 and 2 in CH2Cl2.

PMID- 30212189
TI  - Modulating Aptamer Specificity with pH-Responsive DNA Bonds.
AB  - Aptamers that recognize specific cells in a complex environment have emerged as
      invaluable molecular tools in bioanalysis and in the development of targeted
      therapeutics. The selective recognition of aptamers, however, can be compromised
      by the coexistence of target receptors on both target cells and other cells. To
      address this problem, we constructed a structure-switchable aptamer (SW-Apt) with
      reconfigurable binding affinity in accordance with the microenvironment of target
      cells. The SW-Apt makes use of i-motifs, which are quadruplex structures that
      form in sequences rich in cytosine. More specifically, we report the design of
      single-stranded, pH-responsive i-motif-modified aptamers able to bind
      specifically with target cells by exploiting their pH. Here, the i-motif serves
      as a structural domain to either facilitate the binding ability of aptamers to
      target cells or suppress the binding ability of aptamers to nontarget cell based
      on the pH of the cellular microenvironment. SW-Apt exhibited high binding ability
      with target cells at acidic pH, while no obvious binding was observed at
      physiological pH. The i-motif-induced structure-switching was verified with
      Forster resonance energy transfer and circular dichroism spectroscopy. Notably,
      SW-Apt exhibits high specificity in serum and excellent stability, likely
      attributed to the folded quadruplex i-motif structure. This study provides a
      simple and efficient strategy to chemically modulate aptamer binding ability and
      thus improve aptamer binding specificity to target cells, irrespective of the
      coexistence of identical receptors on target and nontarget cells.

PMID- 30212190
TI  - In Vitro Assessment of Activation of Baikal Seal ( Pusa sibirica) Peroxisome
      Proliferator-Activated Receptor alpha by Polybrominated Diphenyl Ethers.
AB  - We investigated the Baikal seal ( Pusa sibirica) peroxisome proliferator
      activated receptor alpha (bsPPARalpha) transactivation potencies of
      polybrominated diphenyl ethers (PBDEs) using an in vitro bsPPARalpha reporter
      gene assay. BDE47, BDE99, and BDE153 induced bsPPARalpha-mediated transcriptional
      activities in a dose-dependent manner. To compare bsPPARalpha transactivation
      potencies of PBDEs, perfluorooctanoic acid (PFOA)-based relative potencies
      (REPs), a ratio of 50% effective concentration of PFOA to the test chemical, were
      determined. The order of REPs of PBDEs was BDE153 (13) > BDE99 (8.1) > BDE47
      (6.6) > PFOA (1.0) > BDE100, BDE154, and BDE183 (not activated). PBDEs with two
      bromine atoms at the ortho position showed higher bsPPARalpha transactivation
      potencies than those with three bromine atoms. Comparison of the lowest-observed
      effect concentration in bsPPARalpha reporter gene assays revealed that BDE99 was
      7-fold more potent than CB99, a polychlorinated biphenyl congener with the same
      IUPAC number, indicating that brominated congeners could more efficiently
      activate bsPPARalpha than chlorinated congeners. The REPs of PBDEs for
      bsPPARalpha transactivation were approximately 7- to 13-fold higher than those of
      perfluorochemicals (PFCs), suggesting that the effects of PBDEs on the
      bsPPARalpha signaling pathway may be superior to those of PFCs. This study
      provides the first evidence that PBDE congeners activate PPARalpha in vitro.

PMID- 30212191
TI  - Structure and Improved Thermoelectric Properties of Ag2 xCr2-2 xSe3 Compounds.
AB  - This work shows that the thermoelectric properties of Cr2Se3 material are
      improved by doping with Ag. The influence of doping with Ag on the phase
      composition, microstructure, and thermoelectric properties of Ag2 xCr2-2 xSe3 ( x
      = 0-0.02) compounds was thoroughly investigated. Ag atoms prefer to occupy the 6c
      Wyckoff position of the space group, accompanied expansion of the lattice and
      distortion of the octahedral structure units. The electrical conductivity
      increases at elevated temperature, while the lattice thermal conductivity
      decreases significantly through Ag doping, which is primarily attributed to the
      distorted structure and enhanced alloy scattering. Therefore, it produces a peak
      ZT value of 0.27 at 673 K for Ag0.04Cr1.96Se3, which shows an increase of 23%
      compared with that of the undoped Cr2Se3 compound.

PMID- 30212192
TI  - Stereoselective Synthesis of Cyclohexanes via an Iridium Catalyzed (5 + 1)
      Annulation Strategy.
AB  - An iridium catalyzed method for the synthesis of functionalized cyclohexanes from
      methyl ketones and 1,5-diols is described. This process operates by two
      sequential hydrogen borrowing reactions, providing direct access to
      multisubstituted cyclic products with high levels of stereocontrol. This
      methodology represents a novel (5 + 1) strategy for the stereoselective
      construction of the cyclohexane core.

PMID- 30212194
TI  - Synthesis, and Crystal and Electronic Structures, of the Titanium-Rich
      Bismuthides AE3Ti8Bi10 ( AE = Sr, Ba, Eu).
AB  - Three isotypic compounds with the chemical formula AE3Ti8Bi10 ( AE = Sr, Ba, Eu)
      have been obtained via both high-temperature solid state and flux growth
      reactions. Their crystal structure, representing a new type (space group P63/
      mmc, Pearson symbol hP42), features an open framework composed of interlinked
      TiBi5 square pyramids and TiBi6 octahedra. The Ti-Bi substructure is penetrated
      by infinite columns of face-sharing AE6 polyhedra centered by Bi atoms. First
      principle calculations and physical property measurements indicate metallic
      behavior and absence of localized magnetic moments on the Ti atoms. Analysis of
      the chemical bonding reveals strong Ti-Bi and Ti-Ti bonds. The latter demonstrate
      classic two-center, as well as multicenter, interactions.

PMID- 30212195
TI  - Unexpected Solvent Effect in Electrocatalytic CO2 to CO Conversion Revealed Using
      Asymmetric Metalloporphyrins.
AB  - Rapid and efficient electrochemical CO2 reduction is an ongoing challenge for the
      production of sustainable fuels and chemicals. In this work, electrochemical CO2
      reduction is investigated using metalloporphyrin catalysts (metal = Mn, Fe, Co,
      Ni, Cu) that feature one hydroxyphenyl group, and three other phenyl groups, in
      the porphyrin heterocycle (5-(2-hydroxyphenyl)-10,15,20-triphenylporphyrin,
      TPOH). These complexes, which are minimal versions of related complexes bearing
      up to eight proton relays, were designed to allow more straightforward
      determination of the role of the 2-hydroxylphenyl functional group. The iron
      substituted version of TPOH supports robust reduction of CO2 in acetonitrile
      solvent, where carbon monoxide is the only detected product. Addition of weak
      Bronsted acids (1 M water or 8 mM phenol) gives rise to almost 100-fold
      enhancement in turnover frequency. Surprisingly, the iron analogue is a poor
      catalyst when the solvent is changed to dimethylformamide. These results lead to
      the proposal of a model where the hydroxyphenyl group behaves as a local proton
      source, a hydrogen bond donor to CO2-bound intermediates, and a hydrogen bonding
      partner to Bronsted acids. The observations from this model suggest improvements
      for existing electrocatalytic CO2 reduction systems.

PMID- 30212196
TI  - Two Decades under the Influence of the Rule of Five and the Changing Properties
      of Approved Oral Drugs.
AB  - Two decades have passed since the rule of five ushered in the concept of "drug
      like" properties. Attempts to quantify, correlate, and categorize molecules based
      on Ro5 parameters evolved into the introduction of efficiency metrics with far
      reaching consequences in decision making by industry leaders and scientists
      seeking to discover new medicines. Examination of oral drug parameters approved
      before and after the original Ro5 analysis demonstrates that some parameters such
      as clogP and HBD remained constant while the cutoffs for parameters such as
      molecular weight and HBA have increased substantially over the past 20 years. The
      time dependent increase in the molecular weight of oral drugs during the past 20
      years provides compelling evidence to disprove the hypothesis that molecular
      weight is a "drug-like" property. This analysis does not validate parameters that
      have not changed as being "drug-like" but instead calls into question the entire
      hypothesis that "drug-like" properties exist.

PMID- 30212197
TI  - Unique Physicochemical Patterns of Residues in Protein-Protein Interfaces.
AB  - Protein-protein interactions can be characterized by high-resolution structures
      of complexes, from which diverse features of the interfaces can be derived. For
      the majority of protein-protein interactions identified, however, there is no
      information on the structure of the complex or the interface involved in the
      interaction. Understanding what surface properties drive certain interactions is
      crucial in the functional evaluation of protein complexes. Here we show that the
      local patterning of the physicochemical properties of amino acids within surface
      patches is characteristic of interfaces. To describe this feature in a
      quantitative manner, we have defined a statistical potential, iPat, as a measure
      of surface patterning. iPat, which does not take evolutionary conservation or
      knowledge of the interaction partner into consideration, represents a function
      principally different from algorithms that consider intermolecular contacts. We
      assess its suitability for characterizing protein and peptide interfaces, and we
      demonstrate that iPat is uniquely descriptive for interfaces of proteins that
      undergo large conformational changes or that are involved in the binding of
      intrinsically disordered protein (IDP) partners. We suggest that as a stand-alone
      propensity or in combination with other features, iPat represents a new feature
      in analyzing the functional binding specificity of protein-protein interactions
      that has better predictive potential than other simple 1D features, such as
      hydrophobicity or stickiness.

PMID- 30212198
TI  - Antiproliferative Sesquiterpenoids from Ligularia rumicifolia with Diverse
      Skeletons.
AB  - Twenty-two new sesquiterpenoids with four skeletal types and 15 known analogues
      were isolated from the whole plants of Ligularia rumicifolia. The structures of
      the isolates were elucidated based on comprehensive spectroscopic data analysis.
      Compound 1 is a C14 nor-sesquiterpenoid featuring a 6/6/6 tricyclic skeleton with
      a 9,13-ether bridge. The absolute configuration of 2 was established through
      single-crystal X-ray diffraction data. Compounds 13-16 exhibited in vitro
      antiproliferative activity against the four human tumor cell lines A-549, HGC-27,
      HeLa, and MV4-11. Specifically, compounds 13 and 16 showed antiproliferative
      activity against the MV4-11 cell line with IC50 values of 0.5 +/- 0.2 and 1.1 +/-
      0.5 MUM, respectively.

PMID- 30212199
TI  - Approaching Topological Insulating States Leads to High Thermoelectric
      Performance in n-Type PbTe.
AB  - Realizing high thermoelectric performance requires high electrical transport
      properties and low thermal conductivity, which are essentially determined by
      balancing the interdependent controversy of carrier mobility, effective mass, and
      lattice thermal conductivity. Here, we observed an electronic band inversion
      (approaching topological insulating states) in Sn and Se co-alloyed PbTe,
      resulting in optimizing effective mass and carrier mobility. The Sn alloying in
      PbTe(Se) can narrow its band gap due to band inversion and induce a sharper
      conduction band (equals to lower carrier mass), which further facilitates high
      carrier mobility, ~251 cm2 V-1 s-1 in Pb0.89Sn0.11Te0.89Se0.11 at room
      temperature, thus leading to a high power factor. Meanwhile, we found that the
      lattice thermal conductivity kappal can be reduced from ~0.77 Wm-1 K-1 in PbTe to
      ~0.45 Wm-1 K-1 in (Pb0.91Sn0.09)(Te0.91Se0.09) by producing point defects via Sn
      and Se co-alloying. Coupling reducing lattice thermal conductivity with
      integration of optimizing effective mass and carrier mobility by  means of
      electronic band inversion, we obtained a maximum ZT value ~1.4 at 773 K in n-type
      (Pb0.93Sn0.07)(Te0.93Se0.07).

PMID- 30212200
TI  - Method Development and Validation of Indaziflam and Its Five Metabolites in Soil,
      Water, and Fruits by Modified QuEChERS and UHPLC-MS/MS.
AB  - A method for simultaneously determining indaziflam and its five metabolites in
      soil, water, and fruits using ultraperformance liquid chromatography/tandem mass
      spectrometry was established. The analytes were eluted in <4.5 min. Positive
      electrospray ionization mode was used. The analytes were extracted using
      acetonitrile containing 1% ammonium hydroxide, and then the extracts were
      purified using octadecylsilane and PRiME HLB cartridges. The quantification
      limits were 0.01-1.01 MUg kg-1. The linearities of the calibrations for all
      analytes were excellent ( R2 > 0.9952). The recoveries at spike concentrations of
      0.01, 0.1, and 1 mg kg-1 were 81.3-112.1%. The intraday and interday relative
      standard deviations were <13.5% and <12.3%, respectively. The method was
      successfully used to determine indaziflam and its five metabolites in samples
      from markets and fields. The results confirmed that the method is an effective
      and robust procedure for routinely determining indaziflam and its metabolites in
      soil, water, and fruit samples.

PMID- 30212201
TI  - Validation of Matrix Metalloproteinase-9 (MMP-9) as a Novel Target for Treatment
      of Diabetic Foot Ulcers in Humans and Discovery of a Potent and Selective Small
      Molecule MMP-9 Inhibitor That Accelerates Healing.
AB  - Diabetic foot ulcers (DFUs) are a significant health problem. A single existing
      FDA-approved drug for this ailment, becaplermin, is not standard-of-care. We
      previously demonstrated that upregulation of active matrix metalloproteinase
      (MMP)-9 is the reason that the diabetic wound in mice is recalcitrant to healing
      and that MMP-8 participates in wound repair. In the present study, we validate
      the target MMP-9 by identifying and quantifying active MMP-8 and MMP-9 in human
      diabetic wounds using an affinity resin that binds exclusively to the active
      forms of MMPs coupled with proteomics. Furthermore, we synthesize and evaluate
      enantiomerically pure ( R)- and ( S)-ND-336, as inhibitors of the detrimental MMP
      9, and show that the ( R)-enantiomer has superior efficacy in wound healing over
      becaplermin. Our results reveal that the mechanisms of pathology and repair are
      similar in diabetic mice and diabetic humans and that ( R)-ND-336 holds promise
      for the treatment of DFUs as a first-in-class therapeutic.

PMID- 30212202
TI  - Mechanical Unfolding Pathway of the High-Potential Iron-Sulfur Protein Revealed
      by Single-Molecule Atomic Force Microscopy: Toward a General Unfolding Mechanism
      for Iron-sulfur Proteins.
AB  - High-potential iron-sulfur proteins (HiPIPs) are an important class of
      metalloproteins with a [4Fe-4S] cluster coordinated by four cysteine residues.
      Distinct from other iron-sulfur proteins, the cluster in HiPIP has a high
      reduction potential, making it an essential electron carrier in bacterial
      photosynthesis. Here, we combined single-molecule atomic force microscopy and
      protein engineering techniques to investigate the mechanical unfolding mechanism
      of HiPIP from Chromatium tepidum (cHiPIP). We found that cHiPIP unfolds in a two
      step fashion with the protein sequence sequestered by the iron-sulfur center as a
      stable unfolding intermediate state. The rupture of the iron-sulfur center of
      cHiPIP proceeds in two distinct parallel pathways; one pathway involves the
      concurrent rupture of multiple iron-thiolate bonds, and the other one involves
      the sequential rupture of the iron-thiolate bonds. This mechanistic information
      was further confirmed by mutational studies. We found that the rupture of the
      iron-thiolate bonds in reduced and oxidized cHiPIP occurred in the range of 150
      180 pN at a pulling speed of 400 nm/s, similar to that measured for iron-thiolate
      bonds in rubredoxin and ferredoxin. Our results may have important implications
      for understanding the general unfolding mechanism governing iron-sulfur proteins,
      as well as the mechanism governing the mechanical rupture of the iron-sulfur
      center.

PMID- 30212203
TI  - Thermodynamic Scaling of Interfering Hemoglobin Strain Field Waves.
AB  - Hemoglobin (Hgb) forms tetramers (dimerized alpha-beta dimers), which enhance its
      globular stability and may also facilitate small gas molecule transport, as shown
      by recent all-atom Newtonian solvated simulations. Hydropathic bioinformatic
      thermodynamic scaling enables close comparisons of hemoglobin dimers with
      myoglobin and neuroglobin, and reveals many nonlocal wave-like features of
      strained Hgb structures at the coarse-grained amino acid level. The thermodynamic
      analysis employs two hydropathic scales, one describing abrupt first-order
      unfolding transitions, the other continuous second-order transitions. Small
      molecule exchange at hemes is a first-order process. Wave-like collective
      tetrameric features appropriate to ligand absorption and release, seen in optical
      experiments (short times), are identified thermodynamically at long times. Strain
      fields localized near hemes interfere with extended strain fields associated with
      dimer interfacial misfit, resulting in novel wavelength dependent dimer
      correlation function Fano antiresonances.

PMID- 30212204
TI  - Enantioselective Synthesis of Trifluoromethyl alpha,beta-Unsaturated delta
      Lactones via Vinylogous Aldol-Lactonization Cascade.
AB  - The novel vinylogous aldol-lactonization cascade of alkylidene oxindole with
      trifluoromethyl ketones is presented. The reaction, catalyzed by a bifunctional
      tertiary amine, provides an efficient application of the vinylogous reactivity of
      alkylidene oxindoles for the preparation of enantioenriched trifluoromethylated
      alpha,beta-unsaturated delta-lactones.

PMID- 30212205
TI  - Enhancing the Stability of Photogenerated Benzophenone Triplet Radical Pairs
      through Supramolecular Assembly.
AB  - Supramolecular assembly of urea-tethered benzophenone molecules results in the
      formation of remarkably persistent triplet radical pairs upon UV irradiation at
      room temperature, whereas no radicals were observed in solution. The factors that
      lead to emergent organic radicals are correlated with the microenvironment around
      the benzophenone carbonyl, types of proximal hydrogens, and the rigid
      supramolecular network. The absorption spectra of the linear analogues were
      rationalized using time-dependent density functional theory calculations on the
      crystal structure and in dimethyl sulfoxide, employing an implicit solvation
      model to describe structural and electronic solvent effects. Inspection of the
      natural transition orbitals for the more important excitation bands of the
      absorption spectra indicates that crystallization of the benzophenone-containing
      molecules should present a stark contrast in photophysical properties versus that
      in solution, which was indeed reflected by their quantum efficiencies upon solid
      state assembly. Persistent organic radicals have prospective applications ranging
      from organic light-emitting diode technology to NMR polarizing agents.

PMID- 30212206
TI  - Precision DEER Distances from Spin-Label Ensemble Refinement.
AB  - Double electron-electron resonance (DEER) experiments probe nanometer-scale
      distances in spin-labeled proteins and nucleic acids. Rotamer libraries of the
      covalently attached spin-labels help reduce position uncertainties. Here we show
      that rotamer reweighting is essential for precision distance measurements, making
      it possible to resolve Angstrom-scale domain motions. We analyze extensive DEER
      measurements on the three N-terminal polypeptide transport-associated (POTRA)
      domains of the outer membrane protein Omp85. Using the "Bayesian inference of
      ensembles" maximum-entropy method, we extract rotamer weights from the DEER
      measurements. Small weight changes suffice to eliminate otherwise significant
      discrepancies between experiments and model and unmask 1-3 A domain motions
      relative to the crystal structure. Rotamer-weight refinement is a simple yet
      powerful tool for precision distance measurements that should be broadly
      applicable to label-based measurements including DEER, paramagnetic relaxation
      enhancement, and fluorescence resonance energy transfer (FRET).